PMID- 29013714
TI  - Service Notes.

PMID- 29013712
TI  - Autopsy Studies in India.

PMID- 29013713
TI  - Eye Complications of Dermal Leishmaniasis.

PMID- 29013715
TI  - Intrapartum Uterine Rupture. (With a Report on Four Cases).

PMID- 29013716
TI  - Insulin Requirements in India.

PMID- 29013717
TI  - Cement Windows and Ventilators.

PMID- 29013718
TI  - Hydrotherapy in Typhoid Fever.

PMID- 29013719
TI  - A New and Highly Potent Typhoid Vaccine: A Review.

PMID- 29013720
TI  - Pancreatic Calculi.

PMID- 29013721
TI  - Bullous Emphysema of the Lung.

PMID- 29013722
TI  - An Inquiry into the Incidence of Porphyrinuria.

PMID- 29013723
TI  - The School Teacher and Child Welfare.

PMID- 29013724
TI  - Current Topics.

PMID- 29013725
TI  - A Case of Confluent Smallpox: Treatment-Chemotherapy.

PMID- 29013726
TI  - Post-Mortem Examinations in India.

PMID- 29013727
TI  - Hidden Sepsis in the Palatine Tonsils.

PMID- 29013728
TI  - Available Light in a Public Building.

PMID- 29013729
TI  - On the Importance of Malnutrition in the AEtiology of the Anaemic State in Tea
      Garden Coolies.

PMID- 29013731
TI  - Medical News.

PMID- 29013730
TI  - Observations on the Relationship between Malaria and Pistia in Two Villages in
      Murshidabad District.

PMID- 29013732
TI  - Unusual Rhinosporidial Infection in Man.

PMID- 29013733
TI  - Sulphonamide, Sulphates and Ordinary Diet. A Clinical Investigation into the
      Effects of Their Simultaneous Administration.

PMID- 29013734
TI  - Report on the Epidemic of Oriental Sore in Delhi.

PMID- 29013735
TI  - Keratodermia Blennorrhagica. A Brief Review and Report of a Case.

PMID- 29013737
TI  - Erratum: Multiple Primary Epidermoid Carcinoma: De and Tribedi.
AB  - [This corrects the article on p. 397 in vol. 76.].

PMID- 29013736
TI  - Studies on the Vitamin-A Content of Ghee.

PMID- 29013738
TI  - Medical News.

PMID- 29013739
TI  - On the Composition of Buffalo Milk and the Detection of Adulterated Samples
      Passed as Cow Milk.

PMID- 29013740
TI  - Capillaria Hepatica in a Wild Rat in Calcutta.

PMID- 29013742
TI  - Eclampsia Treated with Intravenous Injection of Magnesium Sulphate Solution.

PMID- 29013741
TI  - A Case of Bacillary Dysentery Simulating Acute Abdominal Catastrophy in Its Early
      Stages.

PMID- 29013743
TI  - Effect of Sulphapyridine on Roundworms in a Child with Pneumonia.

PMID- 29013744
TI  - A Case of Disputed Parentage.

PMID- 29013745
TI  - Toxaemia of Pregnancy.

PMID- 29013746
TI  - Does A Lung Cavity Ever Heal Spontaneously?

PMID- 29013747
TI  - Ideal Marriage.

PMID- 29013748
TI  - Mediastinal Hernia.

PMID- 29013749
TI  - Notes on the Training of Athletes.

PMID- 29013750
TI  - A Note on Complement-Fixation Test in Leprosy and Kala-Azar with Witebsky,
      Klingenstein and Kuhn (W. K. K.) Antigen.

PMID- 29013751
TI  - Intradermal Test as an Index of Vitamin-C Nutrition of the Body -Observations at
      Vizagapatam.

PMID- 29013752
TI  - Should Anti-Typhoid Inoculation Be Practised in a Household Exposed to Typhoid
      Infection?

PMID- 29013753
TI  - Service Notes.

PMID- 29013754
TI  - Incidence of Salmonella Infection in Rats in Calcutta.

PMID- 29013755
TI  - Value of Eijkman Test in the Differentiation of AErogenes Isolated from Milk.

PMID- 29013756
TI  - Public Health Reports.

PMID- 29013758
TI  - The Tuberculosis Association of India: The Lady Linlithgow Tuberculosis
      Sanatorium, Kasauli.

PMID- 29013757
TI  - Bacteriophage as an Index of Water Contamination.

PMID- 29013759
TI  - The Public Health Section.

PMID- 29013760
TI  - Current Topics.

PMID- 29013762
TI  - Abstracts from Reports.

PMID- 29013761
TI  - Nutrition.

PMID- 29013763
TI  - Medical News.

PMID- 29013764
TI  - A Case of Peritonitis Following Abortion Treated with Sulphonamide.

PMID- 29013765
TI  - The Intradermal Test as an Index of Vitamin-C Nutrition. Part II.

PMID- 29013766
TI  - Statistical Note.

PMID- 29013767
TI  - Report of Pneumonia Enquiry at the Mayo Hospital, Lahore, during the Years 1938,
      1939 and 1940.

PMID- 29013768
TI  - A New Method for the Relief of Paralysis of the Opponens Pollicis.

PMID- 29013770
TI  - Current Topics.

PMID- 29013769
TI  - Linguatulid Infection in Man.

PMID- 29013772
TI  - Service Notes.

PMID- 29013771
TI  - Subtotal Gastrectomy with Ulcer Exclusion in the Treatment of Chronic Peptic
      Ulcer.

PMID- 29013773
TI  - Medical Notes from the Diaries of the Three Surgeons of Patna-1763.

PMID- 29013775
TI  - Aviation Medicine.

PMID- 29013774
TI  - 'Doping' in Athletic Contests.

PMID- 29013776
TI  - Automatic Flyproof Latrine Seat.

PMID- 29013777
TI  - A Case of Aneurysm of Ascending Aorta.

PMID- 29013778
TI  - Observations on the Outbreak of Epidemic Cerebro-Spinal Meningitis in Burma with
      a Special Note on Its Bacteriology and on Progress of the Epidemic.

PMID- 29013779
TI  - Haematological Technique. Part V.

PMID- 29013780
TI  - Abstracts from Reports.

PMID- 29013781
TI  - Social Aspects of Tuberculosis.

PMID- 29013783
TI  - Abstracts from Reports.

PMID- 29013782
TI  - A Case of Banti's Disease.

PMID- 29013784
TI  - Common Cold Responsible for Grave Suspicion of Rabies in the Dog and a Discussion
      on Associated Considerations Including Rabies in Mongooses and Bats.

PMID- 29013785
TI  - British Pharmaceutical Products.

PMID- 29013787
TI  - Erratum.
AB  - [This corrects the article on p. 175 in vol. 75.].

PMID- 29013786
TI  - Observations on Some Unusual Toxic Effects of Sulphanilamide Therapy.

PMID- 29013788
TI  - 'Non-Epidemic Typhus' Fever in the Civil Population of Bangalore (Civil and
      Military Station).

PMID- 29013789
TI  - British Pharmaceutical Products.

PMID- 29013790
TI  - Service Notes.

PMID- 29013791
TI  - Treatment of Opium Addiction with Lecithin and Glucose and Its Effects on
      Abstinence Symptoms.

PMID- 29013792
TI  - Health Bulletin No. 27. Abstract of the Report of an Inquiry into the Causes of
      Maternal Mortality in Calcutta.

PMID- 29013793
TI  - Hormones in Menstruation and Pregnancy: Physiology, Pathology and Treatment-A
      Resume.

PMID- 29013794
TI  - Current Topics.

PMID- 29013795
TI  - Medical News.

PMID- 29013797
TI  - Maternal Mortality in Calcutta.

PMID- 29013796
TI  - Radiological Appearances of the Heart and Lungs in Cases of Hypertensive Heart
      Failure.

PMID- 29013798
TI  - Observations on the Use of Nicotinic Acid in the Treatment of Pellagra and Allied
      Conditions.

PMID- 29013800
TI  - Current Topics.

PMID- 29013799
TI  - The Buffer Precipitation Test for Malaria (B. P. T.) Adjusted for Large-Scale
      Examinations.

PMID- 29013802
TI  - Medical News.

PMID- 29013801
TI  - A Case of Neuromyelitis Optica.

PMID- 29013803
TI  - Observations on the Differentiation of Bact. Coli and Bact. AErogenes on Levine's
      Simplified Eosin-Methylene-Blue-Agar as Applied to the Bacteriology of Water in
      Bengal.

PMID- 29013804
TI  - Service Notes.

PMID- 29013805
TI  - Abstracts from Reports.

PMID- 29013806
TI  - Report of an Endocrine Clinic.

PMID- 29013807
TI  - Taking Blood for Transfusion (In Potain's Aspirator). Further Details Including
      Cold Storage.

PMID- 29013809
TI  - The Manufacture of Drugs in India.

PMID- 29013808
TI  - The Modern Concept of Uraemia and Its Clinical Study. (Based on a Series of Forty
      Four Cases): Based on a Series of Forty-Four Cases.

PMID- 29013810
TI  - Against Orthodoxies in Symbolism, Micromethods and Micromathematics.

PMID- 29013811
TI  - Vibrio Cholerae and Other Vibrios. (Observations on 'Water Vibrios', with Special
      Reference to Their Variation during Storage in Culture Medium and Possible
      Relationship to Vibrio Cholerae).

PMID- 29013812
TI  - A Few Case Notes on the Use of M. & B. 693 in Pyelitis and in Septic Skin
      Conditions.

PMID- 29013813
TI  - Treatment of Wounds with Urea.

PMID- 29013814
TI  - A Scheme of Control of Tuberculosis in India by 'Organized' Home Treatment.

PMID- 29013815
TI  - Diet in Tuberculosis.

PMID- 29013816
TI  - Pulmonary Tuberculosis and Diabetes Mellitus.

PMID- 29013818
TI  - Medical News.

PMID- 29013817
TI  - Lowering of Insurance Fees.

PMID- 29013819
TI  - Madras Medical Register, 1940-Compilation and Publication of Changes of Addresses
      of Medical Practitioners.

PMID- 29013821
TI  - Service Notes.

PMID- 29013820
TI  - Chronic Non-Tuberculous Infections of the Lung.

PMID- 29013822
TI  - A Pseudo-Tuberculous Condition Associated with Eosinophilia.

PMID- 29013824
TI  - Abstracts from Reports.

PMID- 29013823
TI  - Modern Measures in the Mass Control of Tuberculosis in the United States of
      America.

PMID- 29013825
TI  - Treatment of Tuberculous Empyema Illustrated Report on 17 Cases Treated in the
      Wanless Tuberculosis.

PMID- 29013827
TI  - The Special Tuberculosis Number.

PMID- 29013826
TI  - The Range of the Malaria-Carrying Mosquito.

PMID- 29013828
TI  - A Note on Tuberculosis Surveys.

PMID- 29013829
TI  - Tuberculosis in Women: Pregnancy and Tuberculosis.

PMID- 29013830
TI  - Spontaneous Pneumothorax.

PMID- 29013832
TI  - Current Topics.

PMID- 29013831
TI  - A Tuberculosis Policy for India.

PMID- 29013833
TI  - More Notes on Clinical Heart Disease.

PMID- 29013834
TI  - The Vi-Agglutination Test in Enteric Fever: An Analysis of 255 Cases.

PMID- 29013835
TI  - Prolapse of the Rectum in Children and the Role Played by Gallows Splint in the
      Cure of This Condition.

PMID- 29013836
TI  - A Case of Air Embolism as a Result of Artificial Pneumothorax Treatment.

PMID- 29013837
TI  - Existence of Leptospirosis in Rangoon.

PMID- 29013838
TI  - Auricular Flutter.

PMID- 29013839
TI  - Sub-Lingual Gland Calculi.

PMID- 29013841
TI  - Entomological Specimens.

PMID- 29013840
TI  - A Simple Treatment of Dysenteries and Diarrhoeas.

PMID- 29013842
TI  - An Unusual Case of Anaphylaxis.

PMID- 29013843
TI  - Rabies in Lowlier Animals.

PMID- 29013845
TI  - Medical News.

PMID- 29013844
TI  - On Using Water Instead of Dust for Diluting Paris Green in Malaria Control.

PMID- 29013846
TI  - A Case of Duodenal Obstruction.

PMID- 29013848
TI  - Three Quarters of a Century of Uninterrupted Publication.

PMID- 29013847
TI  - Making Plasma Safe for Transfusion.

PMID- 29013849
TI  - Goitre in the District of Kangra (Punjab).

PMID- 29013850
TI  - Severe Haematuria Resulting from the Use of M.&B. 693.

PMID- 29013851
TI  - Development of Some Female Secondary Sex Characters in an Adult Male.

PMID- 29013852
TI  - Smallpox and Sulphonamide.

PMID- 29013854
TI  - Service Notes.

PMID- 29013853
TI  - A Case of Self-Operation for Ventral Hernia.

PMID- 29013855
TI  - Ectopic Pregnancy: A Clinical Note.

PMID- 29013856
TI  - A Case of Abdominal Pregnancy.

PMID- 29013857
TI  - Abstracts from Reports.

PMID- 29013858
TI  - Intestinal Polyposis.

PMID- 29013859
TI  - Diamidino-Stilbene in the Treatment of Kala-Azar.

PMID- 29013860
TI  - Current Topics.

PMID- 29013861
TI  - Haematological Technique. Part VI.

PMID- 29013862
TI  - The Investigation of Parrots in Calcutta for Presence of Psittacosis and
      Brazilian Virus.

PMID- 29013863
TI  - Banti's Disease?

PMID- 29013864
TI  - Per-Rectum M.&B. 693 in a Case of Pneumonia.

PMID- 29013865
TI  - The Adult of Microfilaria Malayi Brug, 1927.

PMID- 29013866
TI  - Prontosil Album in Gangrenous Stomatitis.

PMID- 29013867
TI  - British Pharmaceutical Products.

PMID- 29013868
TI  - Hospital Organization in India.

PMID- 29013869
TI  - Observations on the Use of Nicotinic Acid in the Treatment of Pellagra and Allied
      Conditions.

PMID- 29013871
TI  - Current Topics.

PMID- 29013870
TI  - Hospital Organization with Special Reference to Conditions in India.

PMID- 29013873
TI  - Service Notes.

PMID- 29013872
TI  - Cardio-Spasm of OEsophagus.

PMID- 29013874
TI  - Topical Application of Sulphanilamides.

PMID- 29013876
TI  - Experience with Diseases of the Gall-Bladder.

PMID- 29013875
TI  - A Simple and Inexpensive Flea-Proof Cage.

PMID- 29013877
TI  - Aortic Stenosis.

PMID- 29013878
TI  - Medical News.

PMID- 29013879
TI  - Haematological Technique. Part II.

PMID- 29013880
TI  - Abstracts from Reports.

PMID- 29013881
TI  - Service Notes.

PMID- 29013882
TI  - Further Light on the Mechanism of Sandfly Transmission of Kala-Azar.

PMID- 29013883
TI  - Acute Obstruction Caused by Meckel's Diverticulum.

PMID- 29013884
TI  - A New Method of Treating Leucoderma.

PMID- 29013885
TI  - An Experiment in Coolie Line Sanitation: Effect on Hookworm Incidence.

PMID- 29013886
TI  - The Venom of Indian Cobra (Naja Naja) in Certain Painful Conditions.

PMID- 29013888
TI  - Current Topics.

PMID- 29013887
TI  - M. and B. 693 in a Case of Pneumonia Complicating a Case of Stab Wound of
      Abdomen.

PMID- 29013889
TI  - General Transposition of Organs.

PMID- 29013890
TI  - A Hydatid Cyst in the Neck.

PMID- 29013891
TI  - Aortalgia or Anginal Pain of Aortic Origin.

PMID- 29013892
TI  - Remarks on the AEtiology and Symptoms of Young-Dah-Hte with a Report on Four
      Cases and Its Medico-Legal Significance.

PMID- 29013893
TI  - Studies in the Epidemiology of Plague in H. E. H. the Nizam's Dominions:
      Comparison of Certain Factors in a Plague-Infected Place with That of
      Neighbouring Plague-Free Area.

PMID- 29013894
TI  - The Treatment of Carbuncle in the Out-Patient Department.

PMID- 29013895
TI  - Observations on the Pathology and Therapy of the So-Called Frontier Sore: Second
      Communication.

PMID- 29013896
TI  - The Transmission of Kala-Azar.

PMID- 29013897
TI  - Haematological Technique. Part I.

PMID- 29013898
TI  - Medical News.

PMID- 29013899
TI  - Abstracts from Reports.

PMID- 29013900
TI  - Vitamin C and Ovulation.

PMID- 29013902
TI  - Circulatory Failure in Typhoid Fever.

PMID- 29013901
TI  - The Needle in the Vein.

PMID- 29013903
TI  - Summaries of the Papers Read and the Discussions That Followed at the
      Tuberculosis Workers' Conference, New Delhi, 20th to 23rd November, 1939.

PMID- 29013905
TI  - Cooley's Erythroblastic Anaemia.

PMID- 29013904
TI  - Epidermophytosis in a Very Young Child.

PMID- 29013907
TI  - Current Topics.

PMID- 29013906
TI  - Different Serological Races of Leptospira in the Andamans.

PMID- 29013908
TI  - A Case of Congenital Diaphragmatic Hernia.

PMID- 29013909
TI  - Correspondence.

PMID- 29013911
TI  - Action of Atebrin on Mental Patients-A Clinical Study.

PMID- 29013910
TI  - Chemotherapeutic Studies in the Treatment of Meningococcal and Pneumococcal
      Meningitis.

PMID- 29013912
TI  - M 3, a New Drug in the Treatment of Malaria.

PMID- 29013913
TI  - A Cure for Scorpion Stings.

PMID- 29013914
TI  - The Place of Electro-Surgery of Tonsils in Indian Practice.

PMID- 29013916
TI  - Tuberculous Endometritis.

PMID- 29013915
TI  - Taking Blood for Transfusion.

PMID- 29013918
TI  - Pernicious Anaemia in Indians.

PMID- 29013917
TI  - A Case of Brucella Abortus Infection Treated with Prontosil.

PMID- 29013919
TI  - Chronic Snake-Bite.

PMID- 29013920
TI  - A Case of Scurvy.

PMID- 29013921
TI  - M. & B. 693 in Indian Strains of Malaria.

PMID- 29013922
TI  - Intracutaneous Inoculation of Guinea-Pigs for the Diagnosis of Tuberculosis.

PMID- 29013923
TI  - Spectrophotometric Examination of Blood in the Treatment of Meningitis with
      Diaminodiphenyl-Sulphone Glucoside.

PMID- 29013924
TI  - A Case of Late Relapse in Typhoid Fever.

PMID- 29013925
TI  - Electrocardiography in the Diagnosis of Silent Heart Diseases.

PMID- 29013926
TI  - Service Notes.

PMID- 29013927
TI  - Abstracts from Reports.

PMID- 29013928
TI  - A Case of Tetanus Treated with 25 per Cent Magnesium Sulphate Solution.

PMID- 29013929
TI  - Report of Two Post-Mortems and Five Cases of Addisonian Pernicious Anaemia.

PMID- 29013930
TI  - A Simple Anaesthetic Apparatus.

PMID- 29013931
TI  - Medical News.

PMID- 29013933
TI  - Vitex Peduncularis in the Treatment of Blackwater Fever.

PMID- 29013932
TI  - Congenital Abnormality of the External Pudendal Veins with Associated Erythema.

PMID- 29013934
TI  - Observations on the Use of Nicotinic Acid in the Treatment of Pellagra and Allied
      Conditions.

PMID- 29013935
TI  - A Dermoid Cyst in the Right Axilla.

PMID- 29013937
TI  - External Bursting of Strangulated Hernia.

PMID- 29013936
TI  - An Outbreak of Epidemic Dropsy.

PMID- 29013938
TI  - M. & B. 693 in Pneumococcal Infection: Two Cases.

PMID- 29013939
TI  - Medical News.

PMID- 29013940
TI  - Current Topics.

PMID- 29013941
TI  - Service Notes.

PMID- 29013942
TI  - Abstracts from Reports.

PMID- 29013943
TI  - The Sterility of the Syringe.

PMID- 29013944
TI  - Quinine and Atebrin in the Control of Malaria; with Special Emphasis on the
      Practical and Economic Viewpoints.

PMID- 29013945
TI  - Observations on Amoebiasis and Its Treatment.

PMID- 29013946
TI  - A Simple Method of Tomography.

PMID- 29013947
TI  - Haematological Technique. Part IV.

PMID- 29013948
TI  - Taking Blood for Transfusion.

PMID- 29013949
TI  - The Medical Profession and First Aid.

PMID- 29013950
TI  - A Simple and Efficient Remedy in the Treatment of Scabies.

PMID- 29013951
TI  - Streptococcus pyogenes in the Throats of a Sample of Healthy Individuals.

PMID- 29013952
TI  - The Mode of Origin and Progress of Anaemia in Pregnant Tea Garden Coolies.

PMID- 29013953
TI  - Role of Oblique Osteotomy of Upper End of Femur in Hip Joint Surgery.

PMID- 29013954
TI  - Natural Leptospiral Infection in the Rat Population of Calcutta.

PMID- 29013955
TI  - Service Notes.

PMID- 29013956
TI  - Drug Manufacture in India during Peace and War.

PMID- 29013957
TI  - Miniature Mass Radiography (A Plea for Its Adoption).

PMID- 29013958
TI  - Haematological Technique Part III.

PMID- 29013959
TI  - Vitex Peduncularis in the Treatment of Blackwater Fever.

PMID- 29013960
TI  - The Destruction of Air-Borne Bacteria.

PMID- 29013961
TI  - Role of X-Ray Screening in Detecting Pulmonary Tuberculosis.

PMID- 29013962
TI  - Crinodora (Palusan) in Indian Strains of Malaria.

PMID- 29013963
TI  - Role of Calcid Fumigation as a Raticidal and Pulicidal Measure in Anti-Plague
      Campaign.

PMID- 29013964
TI  - Note on the Production of Agglutinins in the Blood of Individuals after Peroral
      and Subcutaneous Vaccination by Typhoid and Paratyphoid Vaccines.

PMID- 29013965
TI  - Typhus Fever in Bombay.

PMID- 29013966
TI  - Comparison of Thymol and Some Other Drugs in the Treatment of Hookworm Infection.

PMID- 29013967
TI  - Provision of Latrine Accommodation in Villages.

PMID- 29013969
TI  - Coordination of the Medical Services.

PMID- 29013968
TI  - Haffkinine (Acriquine), an Atebrin-Like Compound Prepared in India, in Indian
      Strains of Malaria.

PMID- 29013970
TI  - Idiopathic Hypochromic Anaemia with a Case Note.

PMID- 29013972
TI  - Medical News.

PMID- 29013971
TI  - A Study on the Toxicity of the Bile Acids and Their Derivatives Prepared from
      Indian Ox Bile.

PMID- 29013973
TI  - Abstracts from Reports.

PMID- 29013974
TI  - Current Topics.

PMID- 29013975
TI  - The Relation of Liver to Other Diseases with Special Reference to Gastro
      Intestinal Disorders and Their Treatment with Intravenous Calcium.

PMID- 29013976
TI  - Haematological Technique. Part V.

PMID- 29013977
TI  - Notes on the Kala-Azar Research in China: The Use of 'Distibinyl' in the
      Treatment of Chinese Kala-Azar.

PMID- 29013978
TI  - Prophylactic Anti-Rabic Vaccine for Animals.

PMID- 29013979
TI  - Service Notes.

PMID- 29013980
TI  - Abstracts from Reports.

PMID- 29013981
TI  - Current Topics.

PMID- 29013982
TI  - A Case of Cerebro-Spinal Fever Cured by Sulphanilamide.

PMID- 29013983
TI  - Uterine Retroversion: A Commentary on the Indications for the Operative
      Correction of Retroversion of the Uterus, Unaccompanied by Prolapse- Illustrated
      by Six Cases.

PMID- 29013984
TI  - Respiratory Dyspnoea Following Administration of Barium Meal.

PMID- 29013985
TI  - Routine Treatment of Epilepsy, with Snake Venom.

PMID- 29013986
TI  - Congenital Cystic Disease of the Lungs.

PMID- 29013987
TI  - Abnormalities of the Suprarenal Gland and Addison's Disease.

PMID- 29013989
TI  - Erratum.
AB  - [This corrects the article on p. 175 in vol. 75.].

PMID- 29013988
TI  - A Method of Removing a Tight Ring from a Finger.

PMID- 29013990
TI  - Wherein Lies the Activity of Sulphanilamide?

PMID- 29013992
TI  - Medical News.

PMID- 29013991
TI  - Use of Hemp Drugs in India.

PMID- 29013993
TI  - Observations on Gastric Acidity in Anaemia.

PMID- 29013995
TI  - The Problem of Drug Addiction.

PMID- 29013994
TI  - Report on Twenty-Four Cases of Tropical Macrocytic Anaemia in Punjabi Men.

PMID- 29013996
TI  - Bacterial Standards for Ice-Cream.

PMID- 29013998
TI  - Sulphonamides and Quinine.

PMID- 29013997
TI  - Service Notes.

PMID- 29013999
TI  - A Vitamin B Deficiency Syndrome Allied to Sprue.

PMID- 29014000
TI  - Quinine Sulphate for Intramuscular Injections.

PMID- 29014002
TI  - Medical News.

PMID- 29014001
TI  - Para-Sprue: A Study of 22 Cases.

PMID- 29014004
TI  - Animal Sera for Transfusion Purposes.

PMID- 29014003
TI  - Somatic Taeniasis (Solium Cysticercosis).

PMID- 29014005
TI  - Quinine and Alstonia Scholaris (Chhatim) in Malaria: A Study of Possible Synergy.

PMID- 29014006
TI  - A New Method of Artificial Respiration.

PMID- 29014007
TI  - Indian Degrees for Indian Graduates.

PMID- 29014008
TI  - Latent Tuberculosis in Medical Students of the King Edward Medical College,
      Lahore, Punjab.

PMID- 29014009
TI  - Current Topics.

PMID- 29014010
TI  - Bilateral Primary Carcinoma of the Fallopian Tubes.

PMID- 29014011
TI  - Para-Sprue.

PMID- 29014012
TI  - Macrocytic Anaemia: The Unknown Haemopoietic Factor in Whole Liver and Yeast.

PMID- 29014013
TI  - Leprosy Control: With Particular Reference to the Madras Presidency.

PMID- 29014014
TI  - A Case of Myasthenia Gravis.

PMID- 29014016
TI  - Indian Degrees for Indian Graduates.

PMID- 29014015
TI  - A Study of the Intradermal Test of Rotter for Vitamin C Status.

PMID- 29014017
TI  - Diet and Hepatitis.

PMID- 29014019
TI  - Erratum: Developing Gametocytes and Schizonts of Plasmodium Falciparum.
AB  - [This corrects the article on p. 458 in vol. 79.].

PMID- 29014018
TI  - Kala-Azar in Bengal: Its Incidence and Trends.

PMID- 29014020
TI  - Ghee as a Source of Vitamin A in Indian Dietaries: The Effect of Cooking on the
      Vitamin Content of Foods.

PMID- 29014021
TI  - The Azygos Lobe.

PMID- 29014022
TI  - Tropical Ulcer in Angul, Orissa.

PMID- 29014023
TI  - Medical Education in India.

PMID- 29014025
TI  - Antimony in Malaria.

PMID- 29014024
TI  - The Influence of Intravenous Injections of Quinine on the Myocardium.

PMID- 29014026
TI  - Organization of Traumatic Surgery and Rehabilitation Service in India.

PMID- 29014027
TI  - Service Notes.

PMID- 29014029
TI  - Medical News.

PMID- 29014028
TI  - Substitute for Cedar Wood Oil for Oil Immersion Work.

PMID- 29014030
TI  - Oriental Sore: Atebrin Treatment.

PMID- 29014032
TI  - Current Topics.

PMID- 29014031
TI  - Nutritional Macrocytic Anaemia Amongst Vegetarians in Forward Areas in the Middle
      East Campaign.

PMID- 29014033
TI  - Treatment of Simian Malaria (P. Knowlesi) with Stilbamidine-M&B 744.

PMID- 29014034
TI  - Abstracts from Reports.

PMID- 29014035
TI  - The British National Health Service.

PMID- 29014036
TI  - A National Health Service. Government Proposals (The White Paper Summarized).

PMID- 29014037
TI  - Observations on Malaria Complicating Kala-Azar.

PMID- 29014039
TI  - Treatment in the Rickettsial Diseases.

PMID- 29014038
TI  - An Unusual Accident.

PMID- 29014040
TI  - Pseudo-Tuberculosis of the Lungs with Eosinophilia, or Benign Eosinophil
      Leukaemia.

PMID- 29014041
TI  - Current Topics.

PMID- 29014042
TI  - Wounds of the Extremities.

PMID- 29014043
TI  - A Case of Lymphosarcoma of the Ileum.

PMID- 29014044
TI  - Determination of Blood Groups from Meals of Blood-Sucking Insects.

PMID- 29014045
TI  - Primary Pneumococcal Sero-Fibrinous Pleurisy.

PMID- 29014046
TI  - Tetanus Neonatorum in the Tropics-A Suggestion for Its Reduction.

PMID- 29014047
TI  - Talipes Equino-Varus.

PMID- 29014049
TI  - Medical News.

PMID- 29014048
TI  - Smallpox in Kweilin, Kwangsi, 1940-1941. An Epidemiological and Clinical Study.

PMID- 29014051
TI  - Wheat and the War.

PMID- 29014050
TI  - Chemical Method of Obtaining Dry Blood Proteins for Transfusion Purposes.

PMID- 29014052
TI  - Humero-Scapular Periarthritis.

PMID- 29014053
TI  - A Neurotic Guilt-Complex Uncovered.

PMID- 29014054
TI  - Pyrogenic Reactions Following Intravenous Saline Infusions.

PMID- 29014055
TI  - Service Notes.

PMID- 29014056
TI  - Smallpox in Calcutta.

PMID- 29014057
TI  - Tuberculosis in India.

PMID- 29014058
TI  - Polyneuritis with Special Reference to the Acute Varieties.

PMID- 29014059
TI  - Vitamin B Deficiency States among Women in Mysore: A Survey of Cases Admitted
      into Female Medical Wards, Krishnarajendra Hospital, Mysore, during 1943.

PMID- 29014060
TI  - Infarction Following the Use of an Abortifacient.

PMID- 29014061
TI  - Bacterium Alcaligenes Infection.

PMID- 29014062
TI  - The Status of Physiology.

PMID- 29014063
TI  - Investigation on Undulant Fever in the City of Bombay.

PMID- 29014064
TI  - Service Notes.

PMID- 29014065
TI  - Bactericidal and Fungicidal Action of Organic Mercurials: With Special Reference
      to the Dermatomycoses.

PMID- 29014066
TI  - A Method for Determining the Temperature of Autoclaves during Sterilization.

PMID- 29014067
TI  - Thymoma.

PMID- 29014068
TI  - Regulation of the Control of Anopheles of the Fluviatilis-Group by Anti-Adult
      Spraying.

PMID- 29014070
TI  - Current Topics.

PMID- 29014069
TI  - Discoloured Cholesterol and Wassermann Antigen: Decreased Fortifying Effect
      Restored by Recrystallization and Washing in Alcohol.

PMID- 29014071
TI  - Pregnancy in a Rudimentary Uterine Horn.

PMID- 29014072
TI  - Intestinal Flora and Nutrition.

PMID- 29014073
TI  - Ventricular Tachycardia of Long Duration (Twenty Days) with Recovery.

PMID- 29014074
TI  - Intestinal Flora and Vitamin B1.

PMID- 29014075
TI  - A Preliminary Note on the Preparation of Anti-Rh Agglutinin.

PMID- 29014076
TI  - Medical News.

PMID- 29014078
TI  - Erratum: Influence of Milk Powder on Fluorine Intoxication in Rats.
AB  - [This corrects the article on p. 249 in vol. 79.].

PMID- 29014077
TI  - A Study of 10,000 Deliveries.

PMID- 29014079
TI  - Abstracts from Reports.

PMID- 29014081
TI  - Primary Atypical Pneumonia.

PMID- 29014080
TI  - Liver Function in Amoebiasis and Its Variations under Emetine Therapy.

PMID- 29014082
TI  - Epidemiology of Cholera in the Punjab.

PMID- 29014083
TI  - Malignant Tumours of the Kidney: Report of a Case of Tubular Adenocarcinoma of
      the Kidney.

PMID- 29014084
TI  - Malaria in the New-Born.

PMID- 29014085
TI  - Sulphanilamide in a Case of Abdominal Injury.

PMID- 29014086
TI  - Cardio-Vascular Syphilis.

PMID- 29014087
TI  - Transmission of Kala-Azar in India: The Case against the Sandfly.

PMID- 29014089
TI  - Medical News.

PMID- 29014088
TI  - Cerebral Malaria: Pathogenesis, Symptoms and Treatment.

PMID- 29014090
TI  - The Preparation of Manure with Night-Soil and Street Rubbish.

PMID- 29014092
TI  - Abstracts from Reports.

PMID- 29014091
TI  - Angioneurotic OEdema Produced by Sulphathiazole.

PMID- 29014093
TI  - The Value of D.E.C. Medium in the Isolation of Intestinal Pathogens.

PMID- 29014094
TI  - The Early Diagnosis of Kala-Azar.

PMID- 29014095
TI  - Anacidity in Gastric Cancer.

PMID- 29014096
TI  - Developing Gametocytes and Schizonts of Plasmodium Falciparum: A Case Showing All
      Stages in the Peripheral Circulation.

PMID- 29014097
TI  - The Value of the Complement-Fixation Test in the Diagnosis of Kala-Azar.

PMID- 29014099
TI  - Current Topics.

PMID- 29014098
TI  - The Quality of Indian-Made Synthetic Drugs. II: Examination of Iodochlorhydroxy
      Quinoline (Enterovioform) of Indian Manufacture.

PMID- 29014100
TI  - Phenamidine in the Treatment of Kala-Azar.

PMID- 29014101
TI  - Fluorine and Fluorosis.

PMID- 29014103
TI  - The Treatment of Mental Disorders Ry Electrically Induced Convulsions.

PMID- 29014102
TI  - A Case of Miliary Tuberculosis of Serous Membranes with a Non-Tuberculous Brain
      Abscess.

PMID- 29014105
TI  - Blackwater Fever and Methaemalbumin.

PMID- 29014104
TI  - Professor Sir Ram Nath Chopra and the Growth of Pharmacology in India.

PMID- 29014106
TI  - Pyrogenic Reactions Following Intravenous Saline Infusions.

PMID- 29014108
TI  - Intravenous Transfusions in Cholera and Other Conditions: A Note on Technique.

PMID- 29014107
TI  - Complement Fixation in Kala-Azar with the WKK Antigen.

PMID- 29014109
TI  - Service Notes.

PMID- 29014110
TI  - An Unusual Case of Coma.

PMID- 29014111
TI  - Chloroform in Cases of Scorpion Bite.

PMID- 29014112
TI  - Epidemic of Typhoid Fever in Surat.

PMID- 29014113
TI  - Effort Syndrome.

PMID- 29014114
TI  - Repetition of the Wassermann Reaction.

PMID- 29014115
TI  - A Case of Typhus Fever Complicating Kala-Azar in Calcutta.

PMID- 29014116
TI  - Sulphadiazine in the Treatment of Bubonic Plague.

PMID- 29014117
TI  - Naga Sore in Jamnagar.

PMID- 29014118
TI  - On the Efficacy of 'Butyl Acridine' in the Treatment of Malaria: A Preliminary
      Note.

PMID- 29014120
TI  - Infarction Following the Use of an Abortifacient.

PMID- 29014119
TI  - The Wassermann Positive Rate of Cases from Hospitals and Venereal Clinics of
      Calcutta in 1939, 1943 and 1944.

PMID- 29014121
TI  - OEdema and Scabies in a Famine Hospital.

PMID- 29014122
TI  - Seasonal Variation in Crime.

PMID- 29014123
TI  - A Case of Benign Tertian Malaria.

PMID- 29014124
TI  - Vitamin-B1 Deficiency.

PMID- 29014125
TI  - The Laboratory in Medical Practice.

PMID- 29014126
TI  - Epitheliomas of the Palate Caused by Smoking of Cigars with the Lighted End
      inside the Mouth.

PMID- 29014127
TI  - A Case of Syphilis of the Stomach.

PMID- 29014129
TI  - Struma Lymphomatosa (Lymphadenoid Goitre: Hashimoto's Disease): A Study of Four
      Cases.

PMID- 29014128
TI  - Formic and Acetic Acids as Poisons.

PMID- 29014130
TI  - The Position of Medical Science in India.

PMID- 29014131
TI  - Struma Lymphomatosa (Hashimoto): A Report of Five Cases.

PMID- 29014132
TI  - Medical Science in India.

PMID- 29014133
TI  - Inanition Cases: A Report.

PMID- 29014134
TI  - A Butyl Acridine Derivative in 'Intestinal Giardiasis': A Preliminary Note.

PMID- 29014135
TI  - Service Notes.

PMID- 29014136
TI  - Malaria in Infants.

PMID- 29014137
TI  - Current Topics.

PMID- 29014138
TI  - Abstracts from Reports.

PMID- 29014139
TI  - Medical News.

PMID- 29014140
TI  - Serum Transfusions in Air-Raid Casualties in South-East Bengal.

PMID- 29014141
TI  - On the Possibility of Using Oil of Turpentine for the Treatment of Scabies.

PMID- 29014142
TI  - Syphilitic Melanosis.

PMID- 29014143
TI  - Hydatid Disease in the Punjab.

PMID- 29014144
TI  - A Bacteriological Study of Curdled Milk (Dahi).

PMID- 29014145
TI  - Gastric Acidity in Health and Disease in India.

PMID- 29014146
TI  - Erratum: Wheeler and Jack's Handbook of Medicine.
AB  - [This corrects the article on p. 55c in vol. 73.].

PMID- 29014147
TI  - The Opium Smoking Habit in India. Part I. General Survey.

PMID- 29014148
TI  - The Radiological Examination of the Stomach and Duodenum.

PMID- 29014150
TI  - The Organism and the Environment.

PMID- 29014149
TI  - Abstracts from Reports.

PMID- 29014152
TI  - Medical News.

PMID- 29014151
TI  - A Crying Need for a Pharmacy Act in India.

PMID- 29014153
TI  - Service Notes.

PMID- 29014154
TI  - Perforation of the Ileum in Suspected Ambulatory Typhoid Treated with
      Establishment of Drainage and Foecal Fistula and Subsequent Enterectomy.

PMID- 29014155
TI  - The Physiology of the Individual in the Tropics Part II.

PMID- 29014156
TI  - The King-Emperor's Fund.

PMID- 29014157
TI  - Arteriography.

PMID- 29014158
TI  - An Unusual Case of Multiple Stones in the Ureter.

PMID- 29014159
TI  - Unusual Case of Urethral Stone.

PMID- 29014160
TI  - Quinine Tolerance in Pregnancy.

PMID- 29014161
TI  - Current Topics.

PMID- 29014162
TI  - A Sub-Phrenic Abscess.

PMID- 29014163
TI  - Salyrgan in Phlegmasia Alba Dolens.

PMID- 29014165
TI  - A Case of Scarlet Fever.

PMID- 29014164
TI  - Spontaneous Infection of Guinea-Pigs with a Spirillum, Presumably Spirillum Minus
      Carter, 1887.

PMID- 29014166
TI  - Adult Haemoglobin Standards in Burma.

PMID- 29014168
TI  - Service Notes.

PMID- 29014167
TI  - The Specific Treatment of Malaria.

PMID- 29014169
TI  - Ichthyol as a Treatment for Guinea-Worm.

PMID- 29014171
TI  - Greasing the Scalp in Hyperpyrexia.

PMID- 29014170
TI  - Anginal Pain in a Case of Malaria.

PMID- 29014172
TI  - Anti-Malarial Measures in the Railway Area at Delhi.

PMID- 29014173
TI  - Dry Cupping and Its Sequel.

PMID- 29014175
TI  - Disaster and Its Moral.

PMID- 29014174
TI  - History of Immunization against Tuberculosis.

PMID- 29014176
TI  - On the Illustration of the Rheumatic Processes in a Modern Museum of Pathology.

PMID- 29014177
TI  - Incidence of Bronchiectasis in Asthma.

PMID- 29014178
TI  - Current Topics.

PMID- 29014180
TI  - Abstracts from Reports.

PMID- 29014179
TI  - Prontosil in Pyelo-Cystitis and Erysipelas.

PMID- 29014181
TI  - A Retro-Peritoneal Suppurating Dermoid in the Region of the Kidney.

PMID- 29014182
TI  - Probable Ring Carcinoma of the Descending Colon; Mango Fibres Obstructing the
      Ring and Causing Complete Obstruction.

PMID- 29014183
TI  - The Hydrogen-Ion Concentration of Human Faeces.

PMID- 29014184
TI  - Present Position of the Opium Smoking Habit in India. Part II: Preparations of
      Opium Used for Smoking and Mode of Indulgence.

PMID- 29014185
TI  - Medical News.

PMID- 29014186
TI  - Service Notes.

PMID- 29014187
TI  - The Research Workers' Conference and Medical Research in India.

PMID- 29014188
TI  - Siphunculina Funicola (Eye-Fly).

PMID- 29014189
TI  - An Interesting Case of Sub-Tertian Malaria.

PMID- 29014190
TI  - A Remarkable Natural Cure of Strangulated Hernia.

PMID- 29014191
TI  - The Chemotherapy of Streptococcal Infections.

PMID- 29014192
TI  - The Physiology of the Individual in the Tropics. Part I.

PMID- 29014193
TI  - Development of Health Education Work in United Provinces.

PMID- 29014195
TI  - Appendicitis in a Case of Transposition of Viscera.

PMID- 29014194
TI  - Some Recent Advances in Surgery.

PMID- 29014196
TI  - Some Unusual Joint Lesions.

PMID- 29014198
TI  - Current Topics.

PMID- 29014197
TI  - A New Filarial Worm from a Human Being.

PMID- 29014199
TI  - Management of Head Injury Cases in Rural Practice.

PMID- 29014201
TI  - Treatment of Ganglion.

PMID- 29014200
TI  - Myeloid Leukaemia Treated by Deep X-Ray Therapy.

PMID- 29014202
TI  - Adult Filarial Worm of Unknown Species Removed from the Skin of a Human Subject.

PMID- 29014203
TI  - Medical News.

PMID- 29014204
TI  - Sternum Puncture. I. The Findings in Normal Indians.

PMID- 29014205
TI  - Experiments on the Spirillum of Rat-Bite Fever.

PMID- 29014206
TI  - Abstracts from Reports.

PMID- 29014207
TI  - Medical Statistics.

PMID- 29014208
TI  - A Lingual Abscess.

PMID- 29014209
TI  - Bertiella studeri, a Natural Tape-Worm Parasite of Monkeys, in a Hindu Child.

PMID- 29014210
TI  - The Ergot Problem and the Practitioner.

PMID- 29014212
TI  - Current Topics.

PMID- 29014211
TI  - A Clinical Investigation on the Value of Proseptasine as a Prophylactic in
      Puerperal Infection.

PMID- 29014213
TI  - Abstracts from Reports.

PMID- 29014214
TI  - The Treatment of Ascariasis.

PMID- 29014215
TI  - Post-Arsphenamine Blood Dyscrasias.

PMID- 29014216
TI  - Medical News.

PMID- 29014217
TI  - Control of Stegomyia fasciata (AEdes AEgypti) Mosquitoes in Indian Country Craft
      by a Mosquito-Proof Metal Cap (Bennett Pattern) for Drinking-Water Receptacles.

PMID- 29014218
TI  - An Unusual Case of Abortion Treated by Curetting.

PMID- 29014219
TI  - Service Notes.

PMID- 29014220
TI  - A Simple Method of Obtaining Hyper-Extension for the Application of a Plaster of
      Paris Jacket in Cases of Fracture of the Thoracic and Lumbar Vertebrae.

PMID- 29014221
TI  - Simple Fractures and Dislocations of the Astragalus.

PMID- 29014222
TI  - Premedication in Sodium Evipan Anaesthesia-A Study of 535 Cases.

PMID- 29014224
TI  - Cinchona Supplies in India.

PMID- 29014223
TI  - On the Necessity of Teaching the Frequency of Rheumatic Infection in Young
      Indians.

PMID- 29014225
TI  - Treatment of Schizophrenia by Inducing Epileptiform Shocks by the Drug Cardiazol:
      An Experimental Study of 42 Cases.

PMID- 29014226
TI  - The Hydrogen-Ion Concentration of Cholera Stools.

PMID- 29014228
TI  - Medical News.

PMID- 29014227
TI  - Observations on the Mottled Condition of Human Teeth Endemic in a Certain
      Locality of Nagercoil in Travancore, S. India.

PMID- 29014230
TI  - Current Topics.

PMID- 29014229
TI  - An Obstetric Cot.

PMID- 29014231
TI  - A Case of Hypernephroma of the Kidney with Secondaries in the Os Calcis and the
      Brain.

PMID- 29014232
TI  - Malaria in Relation to the Coastal Lagoons of Bengal and Orissa.

PMID- 29014234
TI  - World Distribution of Disease : The Changing Picture.

PMID- 29014233
TI  - Experiments on the Stability of Seminal Stains from a Medico-Legal Standpoint.

PMID- 29014235
TI  - A Note on the Therapeutic Efficiency of Soluseptasine in Simian Malaria (P.
      Knowlesi).

PMID- 29014236
TI  - Cholera Epidemics in Burma and the Type of Vibrio Associated with Them.

PMID- 29014238
TI  - Protamine Zinc Insulin.

PMID- 29014237
TI  - Vibrio Cholerae from Material Obtained by Liver Puncture during Life.

PMID- 29014239
TI  - Colour Perception, and Colour-Blindness Tests.

PMID- 29014240
TI  - Some Observations Concerning the Recent Typhoid Epidemic in Calcutta: With a Note
      on Typhoid Myocarditis.

PMID- 29014241
TI  - Anahaemin in Tropical Macrocytic Anaemia.

PMID- 29014242
TI  - A Rat-Flea Survey of Mattanchery (Cochin) (1937).

PMID- 29014243
TI  - Early Ophthalmologists in Calcutta.

PMID- 29014244
TI  - Abstracts from Reports.

PMID- 29014246
TI  - Service Notes.

PMID- 29014245
TI  - Present Position of Anti-Malarial Drug Therapy in India.

PMID- 29014247
TI  - Epidermolysis Bullosa: A Case Report.

PMID- 29014248
TI  - The Treatment of Animals with Antirabic Vaccine.

PMID- 29014249
TI  - The Use of Cobra Venom in Nerve Leprosy.

PMID- 29014250
TI  - Effect of Large Doses of Prontosil.

PMID- 29014251
TI  - Incisional Hernia.

PMID- 29014253
TI  - Diet in Typhoid Fever.

PMID- 29014252
TI  - A Case of Congenital Local Gigantism.

PMID- 29014255
TI  - Enumerative Studies in Benign Tertian Malaria.

PMID- 29014254
TI  - Multiple Perforations of Small Intestine with Recovery.

PMID- 29014256
TI  - A Huge Lipoma of the Breast.

PMID- 29014257
TI  - Hobbs' Treatment with Glycerine Applied to Male Urethra in Gonorrhoea.

PMID- 29014258
TI  - Induction of Labour.

PMID- 29014259
TI  - Fulminant Case of Ulcerative Endocarditis.

PMID- 29014261
TI  - Current Topics.

PMID- 29014260
TI  - Investigation and Conservative Treatment of the Nasal Factor in Asthma.

PMID- 29014262
TI  - Service Notes.

PMID- 29014263
TI  - Follow-Up of a Mass Treatment with Injectable Atebrin.

PMID- 29014264
TI  - Care and After-Care of the Tuberculous.

PMID- 29014266
TI  - Abstracts from Reports.

PMID- 29014265
TI  - Filariasis in the Mikir Hills.

PMID- 29014267
TI  - Traumatic Dislocation of Hip.

PMID- 29014268
TI  - Report of a Case of Early Acquired Syphilis in a Patient with Tertiary Stigmata
      of Untreated Yaws.

PMID- 29014269
TI  - Cardio-Spasm of the OEsophagus.

PMID- 29014270
TI  - Fifty Years of Synthetic Pharmaceutical Research.

PMID- 29014272
TI  - Medical News.

PMID- 29014271
TI  - The Incurables.

PMID- 29014273
TI  - Siphunculina Funicola.

PMID- 29014274
TI  - A Study of the Dietary Habits of Some Communities Living at Calcutta.

PMID- 29014275
TI  - A Case of Adrenal Insufficiency Simulating the Adams-Stokes' Syndrome.

PMID- 29014276
TI  - Leptospirosis.

PMID- 29014277
TI  - Some Clinical Aspects of Anaemia in Pregnancy in Indian Women Living in Bengal.

PMID- 29014278
TI  - A Method of Anti-Larval Oiling for Rivers.

PMID- 29014279
TI  - The Anaemias in Pregnancy: A Haematological, Clinical and Statistical Study.

PMID- 29014281
TI  - Abstracts from Reports.

PMID- 29014280
TI  - Spinal Tumour and Its Diagnosis.

PMID- 29014283
TI  - Medical News.

PMID- 29014282
TI  - A Case of Staphylococcal Polyarthritis.

PMID- 29014284
TI  - Cashew Fruit and Vitamin C.

PMID- 29014286
TI  - Service Notes.

PMID- 29014285
TI  - Aphasia and Complete Right Hemiplegia after Scorpion Bite.

PMID- 29014287
TI  - Mauled by a Leopard.

PMID- 29014288
TI  - Use of Proseptasine in Cellulitis of the Arm.

PMID- 29014289
TI  - The Specific Gravity of Serum of Epidemic Dropsy Patients.

PMID- 29014290
TI  - Short Note on an Epidemic of Chicken Pox in the Central Jail, Cannanore.

PMID- 29014291
TI  - A Case of Chopart's Amputation after 15 Years.

PMID- 29014292
TI  - The Incidence of Rheumatic Infection in India: (As Judged by the Admission and
      Post-Mortem Rates and by the Clinical Experience of Teaching Physicians at the
      Medical Colleges and Schools of Indla): Part II.

PMID- 29014293
TI  - Diet and the Incidence of Disease in India.

PMID- 29014294
TI  - The Guinea-Pig in the Laboratory Diagnosis of Tuberculosis.

PMID- 29014296
TI  - Current Topics.

PMID- 29014295
TI  - Medical Practice in Bengal.

PMID- 29014297
TI  - The Drug Control Bill.

PMID- 29014298
TI  - A Pedicled and Pendulous Lipoma of the Perinaeum.

PMID- 29014299
TI  - A Case of Ascaris Lumbricoides Infection Simulating Cerebral Type of Malaria.

PMID- 29014300
TI  - Abstracts from Reports.

PMID- 29014301
TI  - A Case Note on Cancrum Oris Following Pneumonia Treated by Prontosil.

PMID- 29014303
TI  - Current Topics.

PMID- 29014302
TI  - Medical News.

PMID- 29014304
TI  - The Treatment of Lobar Pneumonia.

PMID- 29014305
TI  - Oxycephaly.

PMID- 29014306
TI  - Cinchona Febrifuge in the Treatment of Malaria.

PMID- 29014307
TI  - Preliminary Report on an Experiment in Coolie-Line Sanitation.

PMID- 29014308
TI  - A Cholera Epidemic in Swat State, N. W. F., 1937.

PMID- 29014309
TI  - A Case of Repeated Abortion Treated with Vitamin E and Proluton.

PMID- 29014310
TI  - A Case of Pellagra Successfully Treated with Intravenous Injections of Sodium
      Thiosulphate.

PMID- 29014311
TI  - An Apparatus for Continuous Oiling of Streams.

PMID- 29014312
TI  - Convulsion Therapy in Schizophrenia.

PMID- 29014313
TI  - Latent Syphilis in the Tropics.

PMID- 29014314
TI  - A Case of Lower Segment Caesarean Section.

PMID- 29014315
TI  - The Bacteriological Examination and the Hydrogen-Ion Concentration of the Urine
      of a Series of 122 Cholera Patients.

PMID- 29014316
TI  - Ectopic Kidney Simulating Ovarian Tumour.

PMID- 29014317
TI  - Service Notes.

PMID- 29014318
TI  - Mental Hygiene and Its Significance.

PMID- 29014319
TI  - A Note on Racial Variations in Leprosy with Particular Reference to Indian and
      Burmese Races.

PMID- 29014321
TI  - Anti-Mosquito Measures in Cantonments with Special Reference to 'Dry Day'
      Instituted in 1927.

PMID- 29014320
TI  - A Case of Tabes Dorsalis in a Hindu.

PMID- 29014322
TI  - Suspected Botulism: A Report on Two Cases.

PMID- 29014323
TI  - Prawns as a Possible Vector of V. Cholerae.

PMID- 29014325
TI  - The Subcutaneous Nodule of Rheumatism.

PMID- 29014324
TI  - Herpes Zoster: Experiments with Tissue Lysate as a Therapeutic Agent.

PMID- 29014326
TI  - The Incidence of Rheumatic Infection in India: (As Judged by the Admission and
      Post-Mortem Rates and by the Clinical Experience of Teaching Physicians at the
      Medical Colleges and Schools of India). Part I.

PMID- 29014327
TI  - Current Topics.

PMID- 29014329
TI  - Gastric Cancer in a Girl of 19.

PMID- 29014328
TI  - Present Position of the Opium Smoking Habit in India. Part III: Studies on the
      Physical and Mental Effects Produced by Opium Smoking. (An Analytical Review of
      300 Opium Smokers Examined in the Field).

PMID- 29014330
TI  - Hydatid Disease.

PMID- 29014331
TI  - A Pseudo-Malignant Tumour of the Ileo-Caecal Region.

PMID- 29014332
TI  - Typhoid Fever Presenting Some Unusual Features.

PMID- 29014334
TI  - Medical News.

PMID- 29014333
TI  - A Case of Breast Cancer in a Male.

PMID- 29014335
TI  - Modified Technique for Phrenic Evulsion.

PMID- 29014336
TI  - Pistia Stratiotes and MF. Malayi.

PMID- 29014338
TI  - Regional Ileitis.

PMID- 29014337
TI  - The Treatment of Splenomegaly by Injections of Milk.

PMID- 29014339
TI  - A Case of Jejunal Diverticulosis.

PMID- 29014340
TI  - Correspondence.

PMID- 29014341
TI  - Conditioned Reflexes.

PMID- 29014342
TI  - Abstracts from Reports.

PMID- 29014343
TI  - Service Notes.

PMID- 29014344
TI  - Siphunculina Funicola (Eye-Fly).

PMID- 29014346
TI  - Service Notes.

PMID- 29014345
TI  - Bacteriophage Treatment of Dysentery in Private Practice.

PMID- 29014347
TI  - King George Thanksgiving (Anti-Tuberculosis) Fund.

PMID- 29014348
TI  - Medical News.

PMID- 29014349
TI  - The Special Tuberculosis Number.

PMID- 29014350
TI  - A Study of the Anti-Tuberculosis Activities in the West, with Some Suggestions
      for the Campaign against Tuberculosis in India.

PMID- 29014351
TI  - Methods of Destruction of Tubercle Bacilli in the Sputum for Use in Indian Homes,
      with Some Experiments.

PMID- 29014352
TI  - B. C. G. Vaccination in Practice.

PMID- 29014355
TI  - The Campaign against Tuberculosis in Italy.

PMID- 29014354
TI  - Role of Solaria in Anti-Tuberculosis Work.

PMID- 29014353
TI  - Anti-Tuberculosis Work in Bengal.

PMID- 29014356
TI  - Abstracts from Reports.

PMID- 29014357
TI  - Deductions from Experience in a Tuberculosis Ex-Patients' Colony in India.

PMID- 29014358
TI  - The Seriousness of Tuberculosis in India as Shown by a Study of Incidence and
      Type.

PMID- 29014360
TI  - A Note for the Guidance of Provincial Organizations.

PMID- 29014359
TI  - Tuberculosis in the Zenana.

PMID- 29014361
TI  - A Time Limit for Using Bacteriophages.

PMID- 29014362
TI  - Incidence of Pulmonary Tuberculosis in the Punjab Villages.

PMID- 29014363
TI  - Illustrations Explaining an Article on 'Siphunculina Funicola (Eye-Fly)'.

PMID- 29014364
TI  - Peptic Ulcer in Northern Circars. A Note on the Incidence.

PMID- 29014365
TI  - Erratum: Bertiella Studeri, a Natural Tape-Worm Parasite of Monkeys, in a Hindu
      Child.
AB  - [This corrects the article on p. 346a in vol. 73.].

PMID- 29014366
TI  - Leptospirosis in India.

PMID- 29014367
TI  - The Effect on Rats of Supplementing a North Indian Diet with Vegetable Proteins
      (Sprouting Pulses) and Calcium.

PMID- 29014369
TI  - Medical News.

PMID- 29014368
TI  - Treatment of Phrynoderma by Vitamin-A Concentrate.

PMID- 29014370
TI  - Studies on the Potency of Prophylactic Vaccines. 1. Cholera Vaccine.

PMID- 29014371
TI  - Benzedrine: Its Use and Abuse.

PMID- 29014372
TI  - Two Cases of Treponemal Infection Treated with Paritran Preparations. Case 2.

PMID- 29014373
TI  - Vitamin B and Peptic Ulcer.

PMID- 29014374
TI  - Abstracts from Reports.

PMID- 29014375
TI  - Volvulus as a Cause of Intestinal Obstruction.

PMID- 29014376
TI  - Current Topics.

PMID- 29014377
TI  - A Case of Extensive Scalding Treated with Cod-Liver Oil Dressing.

PMID- 29014378
TI  - Spinal Anaesthesia.

PMID- 29014379
TI  - Spontaneous Subarachnoid Haemorrhage.

PMID- 29014380
TI  - Two Cases of Treponemal Infection Treated with Paritran Preparations. Case 1.

PMID- 29014381
TI  - A Lympho-Sarcoma in the Bladder.

PMID- 29014383
TI  - Service Notes.

PMID- 29014382
TI  - Variations in the Platelet Count in Typhus Associated with Haematuria.

PMID- 29014384
TI  - Vibrios from Certain Non-Human Sources.

PMID- 29014385
TI  - A Case of Spontaneous Haematomyelia.

PMID- 29014386
TI  - Studies on the Action of Synthetic Drugs on Simian Malaria: Sulphonamide
      Derivatives.

PMID- 29014387
TI  - The Surgical Treatment of Epidemic Dropsy Glaucoma.

PMID- 29014388
TI  - Spondylolisthesis.

PMID- 29014389
TI  - Thyroid Metastases in Bone.

PMID- 29014392
TI  - Abstracts from Reports.

PMID- 29014390
TI  - Chloroform as a Local Anaesthetic.

PMID- 29014391
TI  - Some Epidemiological Features of Plague in Bengal with Special Reference to
      Calcutta.

PMID- 29014394
TI  - Profession of Pharmacy in India.

PMID- 29014393
TI  - The Mortality of Operations for Vesical Calculus in India.

PMID- 29014395
TI  - A Case of Tape-Worm Simulating Acute Appendicitis.

PMID- 29014396
TI  - A Gas Mask for Post-Mortem Work.

PMID- 29014397
TI  - Chemotherapy in Acute Surgical Infections with Prontosil and Allied Drugs.

PMID- 29014398
TI  - Homicide by a Patient Apparently Suffering from Cerebral Malaria.

PMID- 29014399
TI  - Medical News.

PMID- 29014400
TI  - Blood Culture in Cholera.

PMID- 29014401
TI  - Erratum: Latent Syphilis in the Tropics.
AB  - [This corrects the article on p. 585 in vol. 73.].

PMID- 29014402
TI  - Some Observations of Practical Importance and Interest for the Malariologist.

PMID- 29014403
TI  - Studies on the Action of Synthetic Antimalarial Drugs on Indian Strains of
      Malaria: Cilional in the Treatment of 'Crescent Carriers'.

PMID- 29014404
TI  - Spontaneous Rupture of the Heart.

PMID- 29014405
TI  - Anahaemin in Tropical Macrocytic Anaemia.

PMID- 29014407
TI  - Congenital Absence of Eyeballs.

PMID- 29014406
TI  - An Ambulatory Case of Fracture of the Lumbar Vertebrae.

PMID- 29014409
TI  - Current Topics.

PMID- 29014408
TI  - Pre-Cancerous Conditions of the Cervix Uteri and Their Treatment.

PMID- 29014410
TI  - The Isolation of Vibrio cholerae from Non-Cholera Individuals.

PMID- 29014411
TI  - Observation on the Aetiology of Diseases.

PMID- 29014412
TI  - Erratum: Editorial-May 1955.
AB  - [This corrects the article on p. 207 in vol. 90.].

PMID- 29014413
TI  - A Survey of Renal Glycosuria in Indians.

PMID- 29014414
TI  - Fifty Years Ago.

PMID- 29014415
TI  - Some Observations on the Stability of Vitamin C.

PMID- 29014416
TI  - Twenty Five Years Ago.

PMID- 29014418
TI  - Seventy Five Years Ago.

PMID- 29014417
TI  - Refresher Course Series Anaemias-Classification.

PMID- 29014419
TI  - Current Topics, Etc.

PMID- 29014420
TI  - My Pets in India.

PMID- 29014421
TI  - Medical News.

PMID- 29014422
TI  - Freud.

PMID- 29014424
TI  - The Bhakra-Nangal Project.

PMID- 29014423
TI  - Polyarteritis Nodosa.

PMID- 29014425
TI  - The Present State of Knowledge Regarding Biosynthesis of B-Complex Vitamins.

PMID- 29014426
TI  - Estimation of Protein-Proteoses in Crude Liver Extracts for Parenteral Use.

PMID- 29014428
TI  - Twenty Five Years Ago.

PMID- 29014427
TI  - Correspondence.

PMID- 29014429
TI  - Current Topics, Etc.

PMID- 29014430
TI  - Fifty Years Ago.

PMID- 29014432
TI  - Synthetic Antimalarials.

PMID- 29014431
TI  - Bacteriological Diagnosis of Suspected Cholera Cases in the Declining Period of
      an Epidemic.

PMID- 29014433
TI  - Seventy Five Years Ago.

PMID- 29014434
TI  - Fifty Years Ago.

PMID- 29014436
TI  - Seventy-Five Years Ago.

PMID- 29014435
TI  - A System of Automassage.

PMID- 29014437
TI  - Twenty-Five Years Ago.

PMID- 29014439
TI  - Medical Benefits under Employees' State Insurance Scheme.

PMID- 29014438
TI  - Furniture in the Tropics.

PMID- 29014440
TI  - The Physician and the Pharmacist.

PMID- 29014441
TI  - Medical News.

PMID- 29014442
TI  - Current Topics, Etc.

PMID- 29014443
TI  - An Unusual Complication during Suprapubic Prostactamy.

PMID- 29014444
TI  - State Notifications.

PMID- 29014445
TI  - Hormones from Indian Yams.

PMID- 29014446
TI  - Lupus Erythematosus and Collagen Diseases.

PMID- 29014447
TI  - The Total and Differential Leucocyte Count in Brucellosis.

PMID- 29014448
TI  - Bacterial Antagonism between Bacterium Coli and Common Intestinal Pathogens.

PMID- 29014449
TI  - Erratum: An Observation in Photography with X-Ray Films.
AB  - [This corrects the article on p. 556 in vol. 87.].

PMID- 29014451
TI  - A Review of Ringworm of the Hair in India.

PMID- 29014450
TI  - Stevens-Johnson Syndrome Report of a Case Treated with Aureomycin.

PMID- 29014452
TI  - A Case of Post-Kala-Azar Dermal Leishmaniasis.

PMID- 29014453
TI  - A Case of Oriental Sore in Assam.

PMID- 29014454
TI  - Fifty Years Ago.

PMID- 29014456
TI  - Critical Reviews on Tropical Diseases.

PMID- 29014455
TI  - Ectopic Kidney on the Pelvic Brim with Rare Anomalies in the Vascular
      Arrangement.

PMID- 29014457
TI  - Medical News.

PMID- 29014458
TI  - Identification of Relapsing Fever Spirochaetes.

PMID- 29014459
TI  - A Case of Megacolon.

PMID- 29014460
TI  - The Wassermann Reaction in the Tropics.

PMID- 29014461
TI  - Tuberculosis of the Breast.

PMID- 29014462
TI  - Current Topics, Etc.

PMID- 29014463
TI  - Findings in 679 Cases of Kala-Azar in Santal Parganas.

PMID- 29014464
TI  - A Note on the Epidemiology of Cholera and Suggested Lines of Investigation.

PMID- 29014466
TI  - Fifty Years Ago.

PMID- 29014465
TI  - Chloromycetin in Typhoid.

PMID- 29014467
TI  - A Case of Amoebic Abscess of the Liver Treated with Resochin (Chloroquine).

PMID- 29014468
TI  - Intrapleural Pressures on the Contralateral Side in Pleurisy with Effusion.

PMID- 29014470
TI  - World Medicine and Its Links.

PMID- 29014469
TI  - An Unusual Case of Ring-Worm Infection-A Case Report.

PMID- 29014471
TI  - Aureomycin in Brucellosis.

PMID- 29014472
TI  - Untoward (Anaphylactoid) Reaction in I. V. Iron Therapy.

PMID- 29014473
TI  - A Note on the Use and Efficiency of Graded Tuberculin Test in Case Finding and
      Estimation of Prevalence Rate of Pulmonary Tuberculosis.

PMID- 29014475
TI  - Current Topics, Etc.

PMID- 29014474
TI  - Plasma Cytoma.

PMID- 29014476
TI  - Studies in Endemic Fluorosis: Visakhapatnam and Suburban Areas: Distribution of
      Fluorine in Local Waters.

PMID- 29014477
TI  - Medical News.

PMID- 29014478
TI  - Electrical Activity of Epileptic Brains (Study of 150 Cases).

PMID- 29014480
TI  - Fifty Years Ago.

PMID- 29014479
TI  - Angioma of the Vertebra.

PMID- 29014481
TI  - Critical Reviews of Tropical Medicine.

PMID- 29014482
TI  - Chemotherapy of Leishmanial Diseases, a Resume of Recent Researches.

PMID- 29014483
TI  - Chemotherapy of Malaria with Special Reference to the Work Done in India.

PMID- 29014484
TI  - Chemotherapy of Leprosy.

PMID- 29014485
TI  - Erratum: Fifty Years Ago.
AB  - [This corrects the article on p. 51b in vol. 88.].

PMID- 29014486
TI  - Review on the Study of the Skin Diseases in Animals Communicable to Man.

PMID- 29014488
TI  - Any Question.

PMID- 29014487
TI  - Critical Reviews on Tropical Diseases.

PMID- 29014489
TI  - Medical News.

PMID- 29014490
TI  - The Central Control of the Blood Pressure.

PMID- 29014491
TI  - Case Notes of Scabies in a Family Transmitted from Goats.

PMID- 29014492
TI  - Fifty Years Ago.

PMID- 29014493
TI  - Aetiological Role of Toxic Oils in Epidemic Dropsy a Review.

PMID- 29014494
TI  - ACTH Therapy in Pemphigus Vulgaris.

PMID- 29014495
TI  - Erratum: An Observation in Photography with X-Ray Films.
AB  - [This corrects the article on p. 556 in vol. 87.].

PMID- 29014497
TI  - Current Topics, Etc.

PMID- 29014496
TI  - Review on DDT and BHC-The Two New Synthetic Insecticides with Their Principles
      and Practices.

PMID- 29014498
TI  - A Note on the Lepehne-Pickworth Stain.

PMID- 29014499
TI  - Dimorphic Anaemia.

PMID- 29014500
TI  - Kertoderma Blenorrhagica.

PMID- 29014501
TI  - Current Topics, Etc.

PMID- 29014502
TI  - Errata of Dimorphic Anaemia.
AB  - [This corrects the article on p. 126 in vol. 88.].

PMID- 29014503
TI  - Relative Health of Women in Indian Cities.

PMID- 29014504
TI  - Osteogenesis Imperfecta in a Family.

PMID- 29014505
TI  - Normal Haematological Values in Young Punjabi Females.

PMID- 29014506
TI  - Cases of Myiasis in Man Due to Oestrus Ovis Limacus (Sheep Bot).

PMID- 29014507
TI  - Medical News.

PMID- 29014509
TI  - Chlorophyll.

PMID- 29014508
TI  - Isoniazid in the Treatment of a Case of Tuberculous Meningitis in an Adult.

PMID- 29014510
TI  - A Case of Hydatid Cyst of the Broad Ligament.

PMID- 29014511
TI  - A Case of Lipo-Sarcoma.

PMID- 29014513
TI  - Fifty Years Ago.

PMID- 29014512
TI  - Notes on Sand-Flies, Part III.

PMID- 29014514
TI  - Current Topics, Etc.

PMID- 29014515
TI  - Resochin in Malaria.

PMID- 29014516
TI  - Fasciolopsis Buski in Saharsa District (North Bihar).

PMID- 29014518
TI  - Fifty Years Ago.

PMID- 29014517
TI  - Poliomyelitis in Amritsar.

PMID- 29014519
TI  - Annual Science Conference.

PMID- 29014520
TI  - Isonicotonic Acid Hydrazide in the Treatment of Endometrial Tuberculosis.

PMID- 29014521
TI  - Variations of the Basal Body Temperature and Its Clinical Significance.

PMID- 29014522
TI  - A Case of Devic's Disease.

PMID- 29014523
TI  - Synthomycetine (Lepetit) in Typhoid Fever.

PMID- 29014524
TI  - Medical News.

PMID- 29014526
TI  - Correspondence.

PMID- 29014525
TI  - Lactation Following Thoracoplasty Operations.

PMID- 29014528
TI  - Any Questions.

PMID- 29014527
TI  - Vitamin B12 in Macrocytic Anaemia in Pregnancy.

PMID- 29014529
TI  - Current Topics, Etc.

PMID- 29014530
TI  - Allergy and/or Addiction?

PMID- 29014531
TI  - Erratum: Studies on the Hypoglycaemic Effect of Tephrosia Purpurea Var. Pumila.
AB  - [This corrects the article on p. 43 in vol. 86.].

PMID- 29014532
TI  - Medical News.

PMID- 29014533
TI  - Fifty Years Ago.

PMID- 29014534
TI  - Erratum.
AB  - [This corrects the article on p. 78 in vol. 86.].

PMID- 29014535
TI  - Erratum: Evaluation of Blood-Stained C.S.F. as to Its Chemical and Cytological
      Contents.
AB  - [This corrects the article on p. 243 in vol. 86.].

PMID- 29014536
TI  - Transmission of Kala-Azar by Phlebotomus Argentipes.

PMID- 29014537
TI  - Medical News.

PMID- 29014539
TI  - Fifty Years Ago.

PMID- 29014538
TI  - Current Topics, Etc.

PMID- 29014540
TI  - Any Questions.

PMID- 29014541
TI  - Correspondence.

PMID- 29014542
TI  - Fifty Years Ago.

PMID- 29014543
TI  - Correspondence.

PMID- 29014544
TI  - Diet in Ancient Tamil Medical Texts.

PMID- 29014545
TI  - Any Questions.

PMID- 29014546
TI  - Erratum: Newer Antigens, Controls and Types in Complement, in the Serology of
      Syphilis, and Associated Considerations.
AB  - [This corrects the article on p. 359 in vol. 86.].

PMID- 29014547
TI  - Medical News.

PMID- 29014548
TI  - Current Topics, Etc.

PMID- 29014549
TI  - Kala-Azar and the Sandfly.

PMID- 29014550
TI  - Correspondence.

PMID- 29014551
TI  - Correspondence.

PMID- 29014552
TI  - Transmission of Kala-Azar.

PMID- 29014554
TI  - The Anatomical Society of India.

PMID- 29014553
TI  - Correspondence.

PMID- 29014555
TI  - Current Topics, Etc.

PMID- 29014556
TI  - Fifty Years Ago.

PMID- 29014557
TI  - Any Questions.

PMID- 29014559
TI  - Current Topics, Etc.

PMID- 29014558
TI  - Medical News.

PMID- 29014560
TI  - Fifty Years Ago.

PMID- 29014561
TI  - The Recent Calcutta Ghi-Adulteration Case.

PMID- 29014562
TI  - Abstracts from Reports.

PMID- 29014563
TI  - Current Topics, Etc.

PMID- 29014564
TI  - Health of Calcutta.

PMID- 29014565
TI  - Medical News.

PMID- 29014566
TI  - Fifty Years Ago.

PMID- 29014567
TI  - Scorpion Bite.

PMID- 29014568
TI  - Neuromyelitis Optica (Devic's Disease). A Case Report.

PMID- 29014569
TI  - Current Topics, Etc.

PMID- 29014571
TI  - Service Notes.

PMID- 29014570
TI  - The Relationship of the Body-Weight to the Weights of the Organs. The Heart.

PMID- 29014572
TI  - Progesterone in the Treatment of Malaria.

PMID- 29014573
TI  - Any Questions.

PMID- 29014574
TI  - Aeroplane Accident in Calcutta.

PMID- 29014575
TI  - A Case of Tetanus Treated with Penicillin.

PMID- 29014576
TI  - The Precursor of Ascorbic Acid in Vitro.

PMID- 29014578
TI  - Fifty Years Ago.

PMID- 29014577
TI  - Clinical Hydrophobia without Contact with Rabies-Transmitting Animal.

PMID- 29014580
TI  - Polio-Consciousness.

PMID- 29014579
TI  - The Treatment of Female Genital Disorders with Steroid Hormones.

PMID- 29014581
TI  - Snake Bite in India.

PMID- 29014582
TI  - Aureomycin in the Treatment of Typhoid Fever.

PMID- 29014583
TI  - Penicillin in Guinea-Worm Infection.

PMID- 29014585
TI  - Medical News.

PMID- 29014584
TI  - Penicillin Treatment of Vaccine Lymph.

PMID- 29014586
TI  - 'Caduceus'-Or the Significance of Serpents as Emblem of Art of Healing and the
      Snake Worship.

PMID- 29014588
TI  - Plague Complicating Enteric Fever.

PMID- 29014587
TI  - Effect of Sulphadimethylpyrimidine on the Microbial Synthesis of Thiamine and
      Nicotinic Acid in Human Intestine.

PMID- 29014589
TI  - Any Questions.

PMID- 29014590
TI  - Service Notes.

PMID- 29014591
TI  - Acute Anterior Poliomyelitis.

PMID- 29014593
TI  - Abstracts from Reports.

PMID- 29014592
TI  - Teaching of Surgery through Television.

PMID- 29014594
TI  - Fifty Years Ago.

PMID- 29014595
TI  - Streptomycin in Tuberculosis.

PMID- 29014596
TI  - Current Topics, Etc.

PMID- 29014597
TI  - Purification of Vaccine Lymph by Penicillin.

PMID- 29014598
TI  - Medical News.

PMID- 29014600
TI  - Abstracts from Reports.

PMID- 29014599
TI  - Iodine.

PMID- 29014601
TI  - Endothelioma of the Pleura. (With a Case Report).

PMID- 29014602
TI  - Current Topics, Etc.

PMID- 29014603
TI  - Fowler's Position.

PMID- 29014604
TI  - Medical Education in India.

PMID- 29014605
TI  - Some Observations on Accidental Poisoning with Special Reference to Its Incidence
      in Calcutta.

PMID- 29014606
TI  - Allergy-Like Toxic Effect of Sulphathiazole.

PMID- 29014607
TI  - Sodium Sulphacetamide.

PMID- 29014608
TI  - Progressive Muscular Atrophy.

PMID- 29014609
TI  - Service Notes.

PMID- 29014610
TI  - Medical News.

PMID- 29014611
TI  - Bacterium Faecalis Alkaligenes in Calcutta.

PMID- 29014612
TI  - Hyperglycaemia Caused by Prolonged Administration of Insulin.

PMID- 29014613
TI  - Toxic Manifestations of Malaria.

PMID- 29014614
TI  - A Case of Bilateral Abductor Paralysis of the Vocal Cords with Irritation of the
      Right Phrenic Nerve.

PMID- 29014615
TI  - Fifty Years Ago.

PMID- 29014616
TI  - Guinea-Worm Town of Gingee.

PMID- 29014617
TI  - Aureomycin.

PMID- 29014618
TI  - Food and Population.

PMID- 29014619
TI  - Diagnosis of Human Bubonic Plague by Agglutination Test.

PMID- 29014621
TI  - Subsidiary Food Recipes Involving Sweet Potato and Groundnut Cake Flour.

PMID- 29014620
TI  - Notes on Some Remedies. XXXI. Dehydration and Its Treatment. Part III.

PMID- 29014622
TI  - Hyperglycaemia Caused by Prolonged Administration of Insulin.

PMID- 29014623
TI  - Penicillin Sodium in the Treatment of Herpes Ophthalmicus.

PMID- 29014624
TI  - Typhus in the Northern Circars.

PMID- 29014625
TI  - Further Notes on the Incidence of Pneumonic Plague Cases in Gaya (Bihar).

PMID- 29014626
TI  - A Case of Pompholyx.

PMID- 29014627
TI  - Diagnostic Methods in Diseases of the Liver.

PMID- 29014628
TI  - Chloromycetin.

PMID- 29014629
TI  - Medical News.

PMID- 29014630
TI  - Biosynthesis of Ascorbic Acid in Human Beings.

PMID- 29014632
TI  - Fifty Years Ago.

PMID- 29014631
TI  - A Case of Rheumatic Chorea.

PMID- 29014633
TI  - Abstracts from Reports.

PMID- 29014634
TI  - Filarial Eosinophiliosis.

PMID- 29014635
TI  - The Pen.

PMID- 29014636
TI  - A Case of Polymastia.

PMID- 29014638
TI  - Any Questions.

PMID- 29014637
TI  - Current Topics, Etc.

PMID- 29014639
TI  - Road Sickness.

PMID- 29014640
TI  - Service Notes.

PMID- 29014641
TI  - Sporadic Cases of Encephalitis in Rural Bengal.

PMID- 29014642
TI  - Three Unusual Cases of Roundworm Infection.

PMID- 29014643
TI  - Granulosa-Cell Tumour of the Ovary. A Brief Review of Its Important
      Characteristics and a Report of 12 Cases.

PMID- 29014644
TI  - A Case of Meningitis Due to Haemophilus Influenzae.

PMID- 29014645
TI  - Notes on Some Remedies. XXIX. Dehydration and Its Treatment. Part I.

PMID- 29014646
TI  - Commercial and Therapeutic Value of By-Products of Bee Farming Industry in India.

PMID- 29014648
TI  - Penicillin as an Agent for Purifying Smallpox Vaccine (Calf-Propagated Vaccinia
      Virus).

PMID- 29014647
TI  - A Case of Rabies.

PMID- 29014649
TI  - A Monster Resembling a Mermaid (Sea-Nymph).

PMID- 29014651
TI  - Service Notes.

PMID- 29014650
TI  - Relapsing Fever-Tick-Borne. Account of an Outbreak in J.&K. Force, India.

PMID- 29014652
TI  - Treatment for Leucoderma.

PMID- 29014653
TI  - Anaphylactic Shock.

PMID- 29014654
TI  - Private Sanatoria in Cities.

PMID- 29014655
TI  - Fifty Years Ago.

PMID- 29014656
TI  - Any Questions.

PMID- 29014657
TI  - The Vitamins, and Associated Substances and Considerations.

PMID- 29014658
TI  - Lathyrism in Bihar.

PMID- 29014659
TI  - Medical News.

PMID- 29014660
TI  - Current Topics, Etc.

PMID- 29014662
TI  - Medical News.

PMID- 29014661
TI  - Infective Hepatitis.

PMID- 29014663
TI  - Three Cases of Encephalitis Lethargica.

PMID- 29014664
TI  - A Case of Amoebic Vaginitis.

PMID- 29014665
TI  - Unusual Cure of Angina Pectoris after Virus Disease.

PMID- 29014666
TI  - A Case of Myasthenia Gravis.

PMID- 29014667
TI  - A Case of Euwing's Tumour.

PMID- 29014668
TI  - Air-Borne Infection.

PMID- 29014669
TI  - Schilder's Disease.

PMID- 29014670
TI  - Current Topics, Etc.

PMID- 29014672
TI  - Fifty Years Ago.

PMID- 29014671
TI  - Aureomycin in Typhoid Fever. A Preliminary Report of Clinical Trial in Four
      Cases.

PMID- 29014673
TI  - Erratum: A Study in Bengalee and Beharee Female Pelvis by Roentgen-Pelvimetric
      Method a Preliminary Communication.
AB  - [This corrects the article on p. 337 in vol. 84.].

PMID- 29014675
TI  - Hydrogenated Vegetable Oils: Vegetable Ghee.

PMID- 29014674
TI  - A Study of the Bacteriological Types of C. Diphtheriae in Bombay.

PMID- 29014676
TI  - Medical Post-Graduate Courses.

PMID- 29014677
TI  - The Indian Curds or 'Dahi' as a Source of Vitamin B Complex and Growth Factors.

PMID- 29014678
TI  - Amino-Acid Crystals in Urine.

PMID- 29014679
TI  - The King's Demise.

PMID- 29014680
TI  - J.S.B. Stain.

PMID- 29014681
TI  - Current Topics, Etc.

PMID- 29014682
TI  - Fifty Years Ago.

PMID- 29014683
TI  - Any Questions.

PMID- 29014684
TI  - Fifty Years Ago.

PMID- 29014685
TI  - Medical News.

PMID- 29014686
TI  - Medicolegal Number.

PMID- 29014687
TI  - Current Topics, Etc.

PMID- 29014688
TI  - Rabies as a Cause for Man-Eating Propensities of Tiger.

PMID- 29014689
TI  - Current Topics, Etc.

PMID- 29014690
TI  - Medical News.

PMID- 29014692
TI  - International Tuberculosis Campaign and Directorate-General of Health Services,
      New Delhi.

PMID- 29014691
TI  - Any Questions.

PMID- 29014693
TI  - Fifty Years Ago.

PMID- 29014694
TI  - Loose Leaf Binder for I.M.G. Volumes.

PMID- 29014696
TI  - Fifty Years Ago.

PMID- 29014695
TI  - Current Topics, Etc.

PMID- 29014697
TI  - Medical News.

PMID- 29014698
TI  - Fifty Years Ago.

PMID- 29014699
TI  - A Study of the Occupational Lead Hazard in Two Electrical Accumulator Industries.

PMID- 29014700
TI  - Directorate-General of Health Services, New Delhi (India). Monthly Report on
      Tuberculin Testings and BCG Vaccinations.

PMID- 29014701
TI  - Medical News.

PMID- 29014702
TI  - Current Topics, Etc.

PMID- 29014703
TI  - Methylene Blue in the Treatment of Cholera.

PMID- 29014704
TI  - Any Questions.

PMID- 29014705
TI  - Tyrannies of Nomenclature.

PMID- 29014706
TI  - Medicolegal Number.

PMID- 29014707
TI  - A Successful Operation in a Case of Constrictive Pericarditis in Calcutta.

PMID- 29014710
TI  - Fifty Years Ago.

PMID- 29014709
TI  - Weiss Knives.

PMID- 29014711
TI  - Current Topics, Etc.

PMID- 29014713
TI  - Fifty Years Ago.

PMID- 29014712
TI  - Sex Neuroses.

PMID- 29014714
TI  - Infantile Diarrhoea.

PMID- 29014715
TI  - Typhus in Bombay. Part III: Identification of Strains.

PMID- 29014716
TI  - Nutrition of T. N. Medical College Hostel Students.

PMID- 29014717
TI  - The Aim of Medical Inspection of Scholars.

PMID- 29014718
TI  - False Positive Serologic Reactions for Syphilis in Eosinophilia.

PMID- 29014719
TI  - Notes on Some Remedies. XVII. Drugs in Anaemias.

PMID- 29014721
TI  - Treatment of Scabies with D.D.T.

PMID- 29014720
TI  - A Case of Spreading Paralysis.

PMID- 29014722
TI  - International Enemy No. 1: Hurry.

PMID- 29014723
TI  - Medical News.

PMID- 29014724
TI  - Cystic Disease of Lung-A Case Report.

PMID- 29014725
TI  - Short Notes on the Normal Blood Pressure in Indian Females.

PMID- 29014726
TI  - Typhoid Fever in Children Treated with Penicillin and Sulphathiazole.

PMID- 29014727
TI  - Bronchial Carcinoma Simulating Pulmonary Tuberculosis. A Report of Two Cases.

PMID- 29014728
TI  - Current Topics, Etc.

PMID- 29014729
TI  - Industry and Medicine.

PMID- 29014730
TI  - Any Questions.

PMID- 29014731
TI  - A New Operation for Entropion and Trichiasis of the Upper Eyelids.

PMID- 29014732
TI  - Treatment of Infantile Diarrhoea with Phthalylsulphathiazole (M. & B.).

PMID- 29014733
TI  - Intravenous Glucose.

PMID- 29014734
TI  - A Case of Myelomeningocoele.

PMID- 29014735
TI  - Endemic Enteric Fever in a Village.

PMID- 29014736
TI  - A Case of Melioidosis.

PMID- 29014737
TI  - Current Topics, Etc.

PMID- 29014738
TI  - Diabetes Mellitus-Its Manifestations in the Oral Cavity.

PMID- 29014740
TI  - Medical News.

PMID- 29014741
TI  - Books in Running Brooks.

PMID- 29014739
TI  - A Study in Folic Acid.

PMID- 29014742
TI  - Riot Surgery.

PMID- 29014743
TI  - Abstracts from Reports.

PMID- 29014744
TI  - Plasma Concentration of Ascorbic Acid in Health and Pathological Conditions.

PMID- 29014746
TI  - Fifty Years Ago.

PMID- 29014745
TI  - Appendicitis Due to Entamoeba Histolytica.

PMID- 29014747
TI  - The Prevention of Haemolytic Disease of the Newborn by Non-Specific Immunization:
      Experience of a Case.

PMID- 29014748
TI  - A Simple Method of Cutting Serial Sections of Ticks.

PMID- 29014750
TI  - Penicillin Treatment of Early Syphilis.

PMID- 29014749
TI  - The Treatment of Polycythemia by Artificial Infection with Ancylostoma Duodenale.

PMID- 29014751
TI  - Recent Outbreak of Plague in Calcutta.

PMID- 29014752
TI  - Medical News.

PMID- 29014753
TI  - A Short Note on Plague Cases Treated in Campbell Hospital.

PMID- 29014754
TI  - Plague in Calcutta.

PMID- 29014755
TI  - Keratosis Blennorrhagica. A Case Report with a Review of the Literature.

PMID- 29014756
TI  - A Note on the Investigation of Suspected Plague Cases in the Campbell Hospital,
      Calcutta.

PMID- 29014757
TI  - An Interim Note on Certain Features of the Outbreak of Plague in Calcutta during
      March-May 1948. (Corrected up to 10th May.).

PMID- 29014758
TI  - Clinical Impressions of a Second Plague Epidemic in the Same Town.

PMID- 29014759
TI  - The Incidence and Causation of Glycosuria in Pregnancy. Part II.

PMID- 29014760
TI  - An Assessment of the Value of Plague Vaccine (Haffkine Institute) as Used in a
      Single Dose Mass Inoculation. (A Field Enquiry.).

PMID- 29014761
TI  - Service Notes.

PMID- 29014762
TI  - Coccidiosis in the Arakans.

PMID- 29014763
TI  - A Note on Fleas and Rats with Reference to Plague in Calcutta.

PMID- 29014764
TI  - Erratum: Serological Technique (contd.).
AB  - [This corrects the article on p. 31 in vol. 83.].

PMID- 29014765
TI  - Presumptive Malarial Pneumonia.

PMID- 29014766
TI  - Forced Feeding in Acute Dysentery.

PMID- 29014768
TI  - Fifty Years Ago.

PMID- 29014767
TI  - Notes on Some Remedies. XVIII. Drugs in Anaemias. Part II.

PMID- 29014769
TI  - Committee on Indigenous Systems of Medicine. (Government of India, Ministry of
      Health).

PMID- 29014771
TI  - Current Topics, Etc.

PMID- 29014770
TI  - A Presumptive Case of Bicuspid Aortic Valve.

PMID- 29014772
TI  - Plague in Calcutta. Report of the First Case Diagnosed with Photographs of Three
      Other Cases.

PMID- 29014773
TI  - Treatment for Filariasis.

PMID- 29014774
TI  - An Unusual Complication from an Electric Shock.

PMID- 29014775
TI  - Sulphadiazine and Sulphaguanidine in Cholera.

PMID- 29014776
TI  - Granuloma Venereum.

PMID- 29014777
TI  - Emetine-Sulphanilamide Retention Enemas for the Treatment of Amoebic Dysentery.

PMID- 29014779
TI  - Current Topics, Etc.

PMID- 29014778
TI  - Service Notes.

PMID- 29014780
TI  - A Note on Some Public Health Aspects of Tuberculosis.

PMID- 29014781
TI  - Survival of Pneumococci and Streptococci Cultures in the Dry State.

PMID- 29014782
TI  - Serological Technique (Contd.): Complement-Fixation Reaction between Serum
      Protein and Its Antibody for Medico-Legal Purposes.

PMID- 29014783
TI  - Fifty Years Ago.

PMID- 29014784
TI  - Pelvic Floor Repair under Perineo-Pudendal Block Anaesthesia.

PMID- 29014785
TI  - The Relative Susceptibility to Infection and the Response to Immunization of
      Laboratory Animals in India and Abroad.

PMID- 29014787
TI  - Abstracts from Reports.

PMID- 29014786
TI  - Maniacal Symptoms in Ascariasis.

PMID- 29014788
TI  - Incidence of Primary Carcinoma of the Liver and Other Organs as Inferred from
      Autopsy Work, 1926 to 1946.

PMID- 29014789
TI  - Treatment of Balantidial Dysentery with Hydrarg Biniodide.

PMID- 29014790
TI  - Notes on Some Remedies. XVI. Arsenicals in Non-Syphilitic Diseases.

PMID- 29014791
TI  - Typhus in Bombay. Part I: Clinical Features.

PMID- 29014792
TI  - Recognition of M.M.F. under the Schedule to the Indian Medical Council Act.

PMID- 29014794
TI  - Medical News.

PMID- 29014793
TI  - Scrub Typhus (Mite Typhus) in Bombay with a Report on the Isolation of Causal
      Rickettsia.

PMID- 29014795
TI  - Trial of Pentamidine Isothionate in Kala-Azar Cases in the Patna Medical College
      Hospital (Preliminary Report).

PMID- 29014797
TI  - Incongruities in Tuberculosis and Associated Considerations.

PMID- 29014796
TI  - Observations on Pneumococcal Meningitis as a Complication of Kala-Azar.

PMID- 29014798
TI  - Typhus in Bombay. Part II: Epidemiology.

PMID- 29014799
TI  - A Case of Congenital Inguinal Hernia with Polyorchism.

PMID- 29014801
TI  - Giardiasis in Children.

PMID- 29014800
TI  - Excretion of Phosphatases.

PMID- 29014802
TI  - Service Notes.

PMID- 29014803
TI  - Fifty Years Ago.

PMID- 29014804
TI  - Reports and Notifications from the Medical Councils in India.

PMID- 29014805
TI  - The cc., c.cm., MIL., mil., and ml.

PMID- 29014806
TI  - Notes on Some Remedies. XXI. Drugs in Anaemias, Part V.

PMID- 29014807
TI  - Erratum: Presumptive Malarial Pneumonia.
AB  - [This corrects the article on p. 116 in vol. 83.].

PMID- 29014808
TI  - Serological Technique (Contd.): A Microtechnique of Complement Fixation.

PMID- 29014809
TI  - Between Ourselves on Preparing a Typescript, Etc.

PMID- 29014810
TI  - Medical News.

PMID- 29014812
TI  - Current Topics, Etc.

PMID- 29014811
TI  - A Case of Amoebic Pericarditis.

PMID- 29014813
TI  - Observations on an Outbreak of Kala-Azar in Calcutta.

PMID- 29014815
TI  - Abstracts from Reports.

PMID- 29014814
TI  - Scrub Typhus (Tsutsugamushi Disease) in Bombay.

PMID- 29014816
TI  - Air Travel.

PMID- 29014817
TI  - Medical News.

PMID- 29014818
TI  - Choline Dihydrogen Citrate in Infantile Biliary Cirrhosis.

PMID- 29014819
TI  - Role of Palkies (Moving Religious Fairs) in the Epidemiology of Cholera with
      Special Reference to Sri Eknath Maharaj Palki.

PMID- 29014820
TI  - Parkinsonism in Typhoid Fever.

PMID- 29014821
TI  - Histopathological Changes in Liver in Congestive Heart Failure. (Study by Needle
      Biopsy).

PMID- 29014822
TI  - Intrapleural Pressures in Congestive Heart Failure.

PMID- 29014823
TI  - Prize for an Essay on Simple Non-Inflammatory Glaucoma.

PMID- 29014824
TI  - Any Questions.

PMID- 29014825
TI  - Oxytocic Action of Neptal.

PMID- 29014826
TI  - Erratum: Streptomycin.
AB  - [This corrects the article on p. 675 in vol. 82.].

PMID- 29014828
TI  - Rupture of the Uterus.

PMID- 29014827
TI  - International Forms of Certificates of Vaccination against Smallpox and
      Inoculation against Cholera and Yellow Fever.

PMID- 29014829
TI  - Incidence of Coccidiosis in the Arakan.

PMID- 29014830
TI  - Abnormally Long Pregnancy Raises No Presumption of Infidelity.

PMID- 29014831
TI  - Erratum: The Passing of the I.M.S.
AB  - [This corrects the article on p. 411 in vol. 82.].

PMID- 29014832
TI  - An Unusual Case of Suppression of Urine.

PMID- 29014833
TI  - Fifty Years Ago.

PMID- 29014834
TI  - Notes on Some Remedies. XV. Drugs in Syphilis (Contd.).

PMID- 29014835
TI  - Specific for Oriental Sore (Dermal Leishmaniasis).

PMID- 29014836
TI  - Clinical Significance of Hypoproteinaemia.

PMID- 29014837
TI  - Service Notes.

PMID- 29014838
TI  - Serological Technique (Contd.).

PMID- 29014839
TI  - A Plea for Water Pollution Research.

PMID- 29014840
TI  - Blood Grouping Tests Held Not to Be Conclusive Evidence of Paternity.

PMID- 29014841
TI  - AEtiology of Appendicitis. An Experimental Observation.

PMID- 29014842
TI  - Riot Surgery.

PMID- 29014844
TI  - Abstracts from Reports.

PMID- 29014843
TI  - Infantile Diarrhoea.

PMID- 29014845
TI  - Notes on Some Remedies. XIV. Drugs in Syphilis (Contd.).

PMID- 29014847
TI  - A Misplaced Label. Death from Barbitone Poisoning.

PMID- 29014846
TI  - Mepacrine Psychosis.

PMID- 29014848
TI  - Penicillin Administration.

PMID- 29014849
TI  - Serological Technique (Contd.).

PMID- 29014850
TI  - Service Notes.

PMID- 29014852
TI  - Current Topics, Etc.

PMID- 29014851
TI  - Some Experiences in Rural Medical Practice.

PMID- 29014853
TI  - Medical News.

PMID- 29014854
TI  - A Long Gestation Period.

PMID- 29014855
TI  - Streptomycin.

PMID- 29014856
TI  - Fifty Years Ago.

PMID- 29014857
TI  - Medical News.

PMID- 29014858
TI  - Abstracts from Reports.

PMID- 29014859
TI  - Medical Men at the Helm.

PMID- 29014860
TI  - Fifty Years Ago.

PMID- 29014861
TI  - Erratum: Bronchial Carcinoma Simulating Pulmonary Tuberculosis.
AB  - [This corrects the article on p. 83 in vol. 83.].

PMID- 29014862
TI  - A Case of Congenital Absence of the Vagina: Abstract from the Medical Press, Vol
      217, 2nd April, 1947, p.270.

PMID- 29014864
TI  - Insulin Hypoglycaemia.

PMID- 29014863
TI  - Paludrine: Changes in the Doses.

PMID- 29014865
TI  - Pellagra in Rural Bengal.

PMID- 29014866
TI  - Erratum: A Short Note on Plague Cases Treated in Campbell Hospital.
AB  - [This corrects the article on p. 150 in vol. 83.].

PMID- 29014867
TI  - Erratum: Observations on an Outbreak of Kala-Azar in Calcutta.
AB  - [This corrects the article on p. 726 in vol. 82.].

PMID- 29014868
TI  - Erratum: Plague in India.
AB  - [This corrects the article on p. 137 in vol. 83.].

PMID- 29014869
TI  - Carrying Stethoscopes.

PMID- 29014870
TI  - Current Topics, Etc.

PMID- 29014871
TI  - I.M.S. Farewells and Retrospects.

PMID- 29014872
TI  - Tropical Eosinophilia with Melaena as Complication during Arsenical Therapy. A
      Case Report.

PMID- 29014874
TI  - Fifty Years Ago.

PMID- 29014873
TI  - Leucocytes in Normal Rhesus Monkeys.

PMID- 29014875
TI  - Rheumatic Diseases and Mouth Infection.

PMID- 29014876
TI  - Idiopathic Lung Abscess Bursting into the Chest Wall.

PMID- 29014877
TI  - A New Treatment of Scabies.

PMID- 29014878
TI  - Abstracts from Reports.

PMID- 29014879
TI  - Science and International Goodwill.

PMID- 29014880
TI  - Serological Technique (contd.).

PMID- 29014881
TI  - The New Indian Chief of State Medical and Health Services in India.

PMID- 29014882
TI  - Medical News.

PMID- 29014883
TI  - Current Topics, Etc.

PMID- 29014884
TI  - Dissolution of the I.M.S.

PMID- 29014885
TI  - A Case of Appendicitis and Congenital Inguinal Hernia.

PMID- 29014886
TI  - Treatment of Amoebic Liver Abscess with Secondary Infection.

PMID- 29014887
TI  - Evaluation of Prothrombin Response to Vitamin K as Liver Function Test.

PMID- 29014888
TI  - Prognostic Significance of Leucocytic Count in Bubonic Plague.

PMID- 29014889
TI  - Notes on Some Remedies. X. Antimony and Its Derivatives (Part I).

PMID- 29014890
TI  - Strange Thoughts.

PMID- 29014891
TI  - Any Questions.

PMID- 29014893
TI  - The Passing of the I.M.S.

PMID- 29014892
TI  - An Unusual Phenomenon in Strychnine Convulsions.

PMID- 29014894
TI  - Heterozygous Rh Transmission in a Large Family with a Case of Erythroblastosis
      Foetalis.

PMID- 29014895
TI  - Gas Gangrene.

PMID- 29014896
TI  - Service Notes.

PMID- 29014897
TI  - Ultra-Short-Wave Therapy in Medical Practice.

PMID- 29014898
TI  - Lobectomy for Giant Cyst of the Lung.

PMID- 29014899
TI  - Early Diagnosis of Tsutsugamushi.

PMID- 29014900
TI  - Tetrachlorethylene Poisoning and Treatment.

PMID- 29014901
TI  - A Medical Misadventure-Death from Sternal Puncture.

PMID- 29014902
TI  - A Case of Diabetes Insipidus Associated with Diabetes Mellitus.

PMID- 29014903
TI  - Plague Control.

PMID- 29014904
TI  - A Name Misheard.

PMID- 29014906
TI  - Current Topics, Etc.

PMID- 29014905
TI  - Erratum: The Effect of Processing and Souring Milk by the Indigenous Method.
AB  - [This corrects the article on p. 320 in vol. 82.].

PMID- 29014907
TI  - Serological Technique (Contd.).

PMID- 29014908
TI  - An Unusual Case of Suppression of Urine.

PMID- 29014909
TI  - A Case of Hypertensive Encephalopathy with Subarachnoid Haemorrhage in Acute
      Diffuse Glomerulo-Nephritis.

PMID- 29014910
TI  - Suprapubic Prostatectomy with Special Reference to Penicillin Treatment.

PMID- 29014912
TI  - Fifty Years Ago.

PMID- 29014911
TI  - Treatment of Major Burns in 1940 and 1946. Comparison of Tannic Acid Treatment
      with Compression Bandage Method.

PMID- 29014914
TI  - Service Notes.

PMID- 29014913
TI  - Notes on Some Remedies. XI. Antimony and Its Derivatives (Part II).

PMID- 29014915
TI  - Antibiotics.

PMID- 29014917
TI  - Any Questions.

PMID- 29014916
TI  - Delivery of a Dead Foetus per Rectum.

PMID- 29014918
TI  - Abstracts from Reports.

PMID- 29014919
TI  - Blackwater Fever.

PMID- 29014920
TI  - Treatment of Amoebic Dysentery with E.B.I. Retention Enemas.

PMID- 29014922
TI  - The Blood Transfusion Service and Blood Banks in India.

PMID- 29014921
TI  - An Unusual Case of Ileo-Caecal Tuberculosis.

PMID- 29014923
TI  - Experiences of Riot Surgery. A Review of 50 Cases.

PMID- 29014924
TI  - Traumatic Arterial Spasm.

PMID- 29014925
TI  - A Case of Maniacal Excitement Following Large Doses of Atebrin.

PMID- 29014926
TI  - Covenants in Restraint of Competitive Practice.

PMID- 29014927
TI  - Penicillin in Subacute Nephritis.

PMID- 29014928
TI  - Hypoproteinaemia Due to Utilization of Plasma Protein for Erythropoiesis.

PMID- 29014929
TI  - Observations on Anaemia in the Malnad Parts of the Mysore State.

PMID- 29014931
TI  - Medical News.

PMID- 29014930
TI  - Analysis of Surma.

PMID- 29014932
TI  - Further Observations on Plague.

PMID- 29014933
TI  - Arthrodesis of Shoulder : A Case Report.

PMID- 29014934
TI  - Groundnut Cake for Human Consumption.

PMID- 29014935
TI  - A Case of Blackwater Fever.

PMID- 29014936
TI  - Progressive Muscular Atrophy.

PMID- 29014937
TI  - Back Numbers of the I.M.G.

PMID- 29014938
TI  - Oldest Medical Monthly of the Eastern Hemisphere.

PMID- 29014940
TI  - Current Topics, Etc.

PMID- 29014939
TI  - Erratum: Practice of Medicine (Written in Bengali).
AB  - [This corrects the article on p. 500b in vol. 82.].

PMID- 29014941
TI  - Any Questions.

PMID- 29014942
TI  - Planned Parenthood.

PMID- 29014943
TI  - A Case of Diphtheritic Encephalitis.

PMID- 29014944
TI  - Old Calcutta (1759-1763).

PMID- 29014946
TI  - Fifty Years Ago.

PMID- 29014945
TI  - Storage of Penicillin.

PMID- 29014947
TI  - Medical News.

PMID- 29014948
TI  - Service Notes.

PMID- 29014949
TI  - Abstracts from Reports.

PMID- 29014951
TI  - Abortion by Medical Profession.

PMID- 29014950
TI  - Use of Anticoagulants in the Treatment of Experimental Yellow Fever.

PMID- 29014952
TI  - Erratum: Observations on Anaemia in the Malnad Parts of the Mysore State.
AB  - [This corrects the article on p. 488 in vol. 82.].

PMID- 29014953
TI  - Current Topics, Etc.

PMID- 29014954
TI  - V.D. Campaign in Calcutta.

PMID- 29014956
TI  - Medical News.

PMID- 29014955
TI  - Penicillin Therapy in Chancroidal Bubo.

PMID- 29014959
TI  - A Study in the Prevalence of Venereal Disease in India Judged from a Series of
      Routine Kahn Tests and from Histories in Sanatorium Patients.

PMID- 29014957
TI  - Capillarity Phenomena in Gonococcal Infection in the Male Urethra.

PMID- 29014958
TI  - A Case of Syphilis of the Lungs.

PMID- 29014960
TI  - Service Notes.

PMID- 29014962
TI  - Cutaneous Gummata of Face.

PMID- 29014961
TI  - Gonorrhoeal Stricture of the Male Urethra.

PMID- 29014964
TI  - Points from Letters.

PMID- 29014963
TI  - Chief Legal Aspects of the Venereal Diseases.

PMID- 29014965
TI  - Notes on Some Remedies. XIII. Drugs in Syphilis.

PMID- 29014966
TI  - Tropical Eosinophilia and Syphilis. (A Case Report and Commentary.).

PMID- 29014967
TI  - Penicillin Treatment of Early Syphilis.

PMID- 29014969
TI  - Concerning Venereal Diseases.

PMID- 29014968
TI  - Reiter's Disease.

PMID- 29014970
TI  - The Wassermann Positive Rate of Cases from Hospitals and Venereal Clinics of
      Calcutta in 1939, 1943, 1944, 1945 and 1947.

PMID- 29014971
TI  - False Positive Serological Reactions for Syphilis in Smallpox Vaccinations.

PMID- 29014973
TI  - The Rationale of Malaria Therapy in Late Localized Syphilis with Particular
      Reference to General Paralysis of the Insane.

PMID- 29014972
TI  - Serological Technique (Contd.).

PMID- 29014975
TI  - Fifty Years Ago.

PMID- 29014974
TI  - Any Questions.

PMID- 29014976
TI  - Any Questions.

PMID- 29014977
TI  - Abstracts from Reports.

PMID- 29014978
TI  - The Hormones.

PMID- 29014979
TI  - Current Topics, Etc.

PMID- 29014980
TI  - Medical News.

PMID- 29014981
TI  - Medical News.

PMID- 29014982
TI  - Current Topics, Etc.

PMID- 29014983
TI  - Service Notes.

PMID- 29014985
TI  - Polio Yet Again.

PMID- 29014984
TI  - M.D. and M.S., Bombay.

PMID- 29014986
TI  - Fifty Years Ago.

PMID- 29014987
TI  - Clinical Hydrophobia without Contact with Rabies Transmitting Animal.

PMID- 29014988
TI  - Sudden Death of Babies.

PMID- 29014989
TI  - Medical Correspondence College.

PMID- 29014990
TI  - Typhus in the Northern Circars.

PMID- 29014991
TI  - Medical News.

PMID- 29014992
TI  - Abstracts from Reports.

PMID- 29014993
TI  - Combination of Liver Extract and Folic Acid.

PMID- 29014994
TI  - Current Topics, Etc.

PMID- 29014995
TI  - Treatment of Malaria.

PMID- 29014996
TI  - The Birth of the Indian Republic.

PMID- 29014997
TI  - Fifty Years Ago.

PMID- 29014998
TI  - Abstracts from Reports.

PMID- 29014999
TI  - An Appeal.

PMID- 29015001
TI  - Service Notes.

PMID- 29015000
TI  - Geriatric Medicine.

PMID- 29015002
TI  - Heparin in Yellow Fever.

PMID- 29015003
TI  - Penicillin and Sulphadiazine in Lobar Pneumonia.

PMID- 29015004
TI  - I.M.G. Previous Issues.

PMID- 29015005
TI  - Medical News.

PMID- 29015006
TI  - Current Topics, Etc.

PMID- 29015007
TI  - Fifty Years Ago.

PMID- 29015008
TI  - Erratum: The Vitamins, and Associated Substances and Considerations.
AB  - [This corrects the article on p. 453 in vol. 84.].

PMID- 29015009
TI  - Unusual Cure of Angina Pectoris after Virus Disease.

PMID- 29015010
TI  - Pleasant 1949-50 Winter in Calcutta and Associated Considerations.

PMID- 29015011
TI  - Service Notes.

PMID- 29015012
TI  - Abstracts from Reports.

PMID- 29015013
TI  - Fifty Years Ago.

PMID- 29015015
TI  - Medical News.

PMID- 29015014
TI  - Wassermann Reaction.

PMID- 29015016
TI  - Current Topics, Etc.

PMID- 29015017
TI  - Precautionary Measures in the Management of Pneumonic Plague.

PMID- 29015019
TI  - Against Pessimism in Tuberculosis.

PMID- 29015018
TI  - A Note on Filing Medical Journals.

PMID- 29015020
TI  - Fifty Years Ago.

PMID- 29015021
TI  - Current Topics, Etc.

PMID- 29015022
TI  - Penicillin Treatment of Glycerine Vaccine Lymph.

PMID- 29015023
TI  - Medical News.

PMID- 29015024
TI  - Fifty Years Ago.

PMID- 29015026
TI  - Any Questions.

PMID- 29015025
TI  - Erratum: Use of D.D.T. as a Plague Control Measure in the Bombay State.
AB  - [This corrects the article on p. 217 in vol. 87.].

PMID- 29015028
TI  - Current Topics, Etc.

PMID- 29015027
TI  - Inoculation against Preventable Diseases.

PMID- 29015029
TI  - Erratum: Pyogenic Arthritis and Osteom Yelitis Following Smallpox (A Report of 21
      Cases).
AB  - [This corrects the article on p. 244 in vol. 87.].

PMID- 29015031
TI  - Fire Side Fantasies.

PMID- 29015030
TI  - Carcinoid of the Appendix.

PMID- 29015032
TI  - Branchial Fistula: Report of a Case.

PMID- 29015033
TI  - Vomiting, a Sign of Angina Pectoris.

PMID- 29015034
TI  - A Case of Strangulated Inguinal Hernia in a Patient Aged 107 Years Treated
      Successfully by Operations.

PMID- 29015035
TI  - Medical News.

PMID- 29015037
TI  - Fifty Years Ago.

PMID- 29015036
TI  - The Effect of Digitalis on the Coagulation Time of Blood.

PMID- 29015038
TI  - Cashew-Nut (Anacardium Accidentale Linn) Shell Oil as an Anthelmintic in Human
      Helminthiasis-A Preliminary.

PMID- 29015040
TI  - Misuse of Wonder Drugs.

PMID- 29015039
TI  - Clinical Assesment of Nutritional Status of School Boys in Uttar Pradesh.

PMID- 29015041
TI  - Current Topics, Etc.

PMID- 29015042
TI  - Osteitis Pubis.

PMID- 29015043
TI  - An Observation in Photography with X-Ray Films.

PMID- 29015044
TI  - Multiocular Dentigerous Cyst.

PMID- 29015045
TI  - Serological Technique: Immunotherapy.

PMID- 29015046
TI  - Directorate-General of Health Services, New Delhi.

PMID- 29015048
TI  - Current Topics, Etc.

PMID- 29015047
TI  - A Rare Variety of Surgical Emphysema.

PMID- 29015049
TI  - Medical News.

PMID- 29015050
TI  - Controversy over BCG Vaccination.

PMID- 29015051
TI  - Fifty Years Ago.

PMID- 29015052
TI  - Current Topics, Etc.

PMID- 29015053
TI  - Any Questions.

PMID- 29015054
TI  - Fifty Years Ago.

PMID- 29015055
TI  - Erratum: A Case of Strangulated Inguinal Hernia, Right Side, with a Peculiar
      Complication.
AB  - [This corrects the article on p. 203 in vol. 87.].

PMID- 29015056
TI  - Erratum: Studies in the Histology of Early Lesions in Leprosy.
AB  - [This corrects the article on p. 225 in vol. 87.].

PMID- 29015057
TI  - Criteria for Discharge of a Patient from a Leprosy Home: (With Special Reference
      for Re-Appointment by Employer).

PMID- 29015059
TI  - Fifty Years Ago.

PMID- 29015058
TI  - Diamino-Diphenyl-Sulphone (DDS) in the Treatment of Filariasis.

PMID- 29015060
TI  - Pneumococeal Meningitis with Multiple Cranial Nerve Lesions.

PMID- 29015062
TI  - Any Questions.

PMID- 29015061
TI  - Phenyl Pyruvic Oligophrenia: Short Review with the Report of an Affected Family.

PMID- 29015063
TI  - Intramuscular Paraldehyde.

PMID- 29015064
TI  - An Atypical Case of Pneumococcal Meningitis.

PMID- 29015065
TI  - Guinea-Worm Disease: Case Notes.

PMID- 29015066
TI  - A Case of Amoebic Perforation of the Colon.

PMID- 29015067
TI  - Too Much Latin and Greek (From Edinburg Review, Oct., 1809, as Reproduced in
      Master Piece of the World's Best Literature).

PMID- 29015068
TI  - From a Distinguished Contributor.

PMID- 29015069
TI  - Thymol Turbidity as a Liver Function Test.

PMID- 29015071
TI  - Current Topics, Etc.

PMID- 29015070
TI  - A Case of Reticulum-Cell Sarcoma.

PMID- 29015072
TI  - The Ratio of the Body Weight to the Weights of the Organs Part IV. The Kidneys'
      the Spleen, the Liver, the Lungs, the Pancreas, the Pituitary, the Suprarenals,
      the Thyriod and the Testes.

PMID- 29015073
TI  - Ourselves.

PMID- 29015074
TI  - Study of a New Modified Insulin (Type N.P.H.).

PMID- 29015075
TI  - Medical News.

PMID- 29015076
TI  - Correspondence.

PMID- 29015077
TI  - Perforation of the Aorta by Swallowed Fish Bone.

PMID- 29015078
TI  - Tendoachillis as a Measure of Somatie and Psychosomatie Wellbeing.

PMID- 29015079
TI  - The Reduction of Leprosy Incidence by Insolation of Infective Cases, Combined
      with Six-Monthly Surveys of All Contacts to Detect New Cases in an Easily Curable
      Stage.

PMID- 29015080
TI  - A Noteworthy Case for Diagnosis.

PMID- 29015081
TI  - 59th Annual Meeting of the Association of Military Surgeons of the United States.

PMID- 29015082
TI  - Polyarteritis Nodosa: Report of a Case.

PMID- 29015083
TI  - Isonicotinic Acid Hydrazide.

PMID- 29015084
TI  - Any Questions.

PMID- 29015085
TI  - A Case Report on Haemangioendothelioma Sarcoma of Liver.

PMID- 29015088
TI  - Treatment of Cholera with Oral and Intravenous Chloromycetin.

PMID- 29015087
TI  - Naturally Developed Diphtheria Antitoxin Titre of a Random Indian Population.

PMID- 29015086
TI  - Notes on the Haematological Studies in Children in Poona.

PMID- 29015089
TI  - Fifty Years Ago.

PMID- 29015090
TI  - Current Topics, Etc.

PMID- 29015091
TI  - Studies in Yaws (Koya Rogam): A Review of 1,000 Cases of Yaws from Warangal
      District, Hyderabad State (Deccan).

PMID- 29015093
TI  - Erratum: Controversy over BCG Vaccination.
AB  - [This corrects the article on p. 410 in vol. 87.].

PMID- 29015092
TI  - A Preliminary Note on the Prophylactic Value of Fortnightly Doses of Camoquin in
      Malaria.

PMID- 29015094
TI  - Scabies in Goats and Rabbits Communicable to Man: With Case Reports.

PMID- 29015095
TI  - Avitaminosis in Kala-Azar: Preliminary Observations.

PMID- 29015096
TI  - Medical News.

PMID- 29015097
TI  - Treatment of Indian Kala-Azar with a New Antimony Compound: Nu-1160.

PMID- 29015098
TI  - Current Topics, Etc.

PMID- 29015099
TI  - Medical News.

PMID- 29015100
TI  - The Radioactive Isotopes.

PMID- 29015101
TI  - Care and Management of Laboratory Animals.

PMID- 29015102
TI  - Fifty Years Ago.

PMID- 29015103
TI  - Spontaneous Lactation.

PMID- 29015104
TI  - Choline Content of Milk.

PMID- 29015105
TI  - Tuberculosis in Indian Prisons Fifty Years Ago.

PMID- 29015106
TI  - Fifty Years Ago.

PMID- 29015107
TI  - Tuberculosis in Europe To-Day.

PMID- 29015108
TI  - Transmission of Kala-Azar by Phlebotomus Argentipes.

PMID- 29015109
TI  - Research on Bhagavad Gita.

PMID- 29015110
TI  - Abstracts from Reports.

PMID- 29015111
TI  - Current Topics, Etc.

PMID- 29015112
TI  - Medical News.

PMID- 29015113
TI  - Any Questions.

PMID- 29015114
TI  - Fifty Years Ago.

PMID- 29015115
TI  - Current Topics, Etc.

PMID- 29015116
TI  - Preliminary Note on a New Method of Treating Malarial Fevers.

PMID- 29015117
TI  - Apropos of the Problem Families in Europe and Asia.

PMID- 29015118
TI  - Choline Content of Milk.

PMID- 29015120
TI  - Current Topics, Etc.

PMID- 29015119
TI  - Fifty Years Ago.

PMID- 29015121
TI  - Abstracts from Reports.

PMID- 29015122
TI  - A Substitute for Morphine. A Preliminary Communication.

PMID- 29015124
TI  - Medical News.

PMID- 29015123
TI  - Any Questions.

PMID- 29015125
TI  - Blood Types M and N.

PMID- 29015126
TI  - Current Topics, Etc.

PMID- 29015127
TI  - Fifty Years Ago.

PMID- 29015128
TI  - Medical News.

PMID- 29015129
TI  - Vitamin M, Wills' Factor and Folic Acid.

PMID- 29015130
TI  - Behind Time Again.

PMID- 29015131
TI  - Sanitation and Other Allied Matters at Big Indian Railway Stations.

PMID- 29015132
TI  - Any Questions.

PMID- 29015133
TI  - Fifty Years Ago.

PMID- 29015135
TI  - Current Topics, Etc.

PMID- 29015134
TI  - Erratum: Serological Technique: Immunotherapy (Contd.).
AB  - [This corrects the article on p. 47 in vol. 86.].

PMID- 29015136
TI  - Transmission of Kala-Azar by Phlebotomus Argentipes.

PMID- 29015137
TI  - Death after Anti-Rabies Treatment.

PMID- 29015139
TI  - Glucose Injection.

PMID- 29015138
TI  - Service Notes.

PMID- 29015140
TI  - Current Topics, Etc.

PMID- 29015141
TI  - Medical Councils.

PMID- 29015142
TI  - A Marvel of Human Brain Power: Helen Keller, LL.D., L.H.D., Blind-Deaf Author
      Educator.

PMID- 29015143
TI  - Morphologic Changes in Coronary Heart Disease.

PMID- 29015144
TI  - Notes on Some Remedies. XXV. Blood Transfusion, Part IV.

PMID- 29015146
TI  - Medical News.

PMID- 29015145
TI  - Erratum: Allergy: Newer Knowledge.
AB  - [This corrects the article on p. 565 in vol. 83.].

PMID- 29015147
TI  - Fifty Years Ago.

PMID- 29015148
TI  - Congenital Absence of the Uterus.

PMID- 29015149
TI  - Any Questions.

PMID- 29015150
TI  - Hydroxy Stilbamidine in the Treatment of Kala-Azar.

PMID- 29015151
TI  - A Neurological Case for Diagnosis.

PMID- 29015153
TI  - Current Topics, Etc.

PMID- 29015152
TI  - Erratum: Serological Technique (Contd.).
AB  - [This corrects the article on p. 549 in vol. 83.].

PMID- 29015155
TI  - Service Notes.

PMID- 29015154
TI  - Medical News.

PMID- 29015157
TI  - Typhus Fevers.

PMID- 29015156
TI  - Serological Technique (Contd.).

PMID- 29015158
TI  - Fifty Years Ago.

PMID- 29015159
TI  - Skin-Grafting.

PMID- 29015160
TI  - Notes on Some Remedies XXVIII. Drugs in Helminthic Diseases, Part III.

PMID- 29015161
TI  - Any Questions.

PMID- 29015162
TI  - Serological Technique (Contd.).

PMID- 29015163
TI  - Changes in the Dosage of Paludrine.

PMID- 29015165
TI  - Service Notes.

PMID- 29015164
TI  - The King's Health.

PMID- 29015166
TI  - Pneumonic Plague in Eastern India.

PMID- 29015167
TI  - Current Topics, Etc.

PMID- 29015168
TI  - Medical News.

PMID- 29015169
TI  - Fifty Years Ago.

PMID- 29015170
TI  - Microfilm Service Units.

PMID- 29015171
TI  - Tuberculosis.

PMID- 29015172
TI  - Abstracts from Reports.

PMID- 29015173
TI  - Notes on Some Remedies. XXVII. Drugs in Helminthic Diseases, Part II.

PMID- 29015174
TI  - Serological Technique (Contd.).

PMID- 29015175
TI  - Erratum: Serological Technique (Contd.).
AB  - [This corrects the article on p. 51 in vol. 84.].

PMID- 29015176
TI  - Medical News.

PMID- 29015177
TI  - Fifty Years Ago.

PMID- 29015178
TI  - Service Notes.

PMID- 29015179
TI  - Erratum: A Report of 46 Cases of Anaemia in the Punjab with Special Reference to
      Nutritional Macrocytic and Addisonian Anaemia.
AB  - [This corrects the article on p. 508 in vol. 83.].

PMID- 29015180
TI  - Corneal Grafting in India.

PMID- 29015181
TI  - Antrycide.

PMID- 29015182
TI  - Current Topics, Etc.

PMID- 29015183
TI  - B.C.G. Vaccine.

PMID- 29015184
TI  - Fifty Years Ago.

PMID- 29015185
TI  - Incidence and Control of Kala-Azar in the Eastern Districts of United Provinces.

PMID- 29015187
TI  - Pleasant Hot Weather in Calcutta in 1949.

PMID- 29015186
TI  - Chemotherapy in Human Anthrax.

PMID- 29015188
TI  - Pulmonary Amoebiasis.

PMID- 29015189
TI  - Erratum: Pneumonic Plague in Eastern India.
AB  - [This corrects the article on p. 157b in vol. 84.].

PMID- 29015190
TI  - Enlarged Prostate, Clinical Features, Diagnosis and Management. (A Report of 12
      Cases.).

PMID- 29015191
TI  - Studies on the Hypoglycaemic Effect of Tephrosia Purpurea Var. Pumila.

PMID- 29015192
TI  - Current Topics, Etc.

PMID- 29015193
TI  - Medical News.

PMID- 29015194
TI  - Service Notes.

PMID- 29015195
TI  - Any Questions.

PMID- 29015196
TI  - Serological Technique: Immunotherapy (Contd.). Immunization against Viral
      Infections.

PMID- 29015198
TI  - OEdema during Recovery from Anaemia Due to Red Cell Regeneration
      Hypoproteinaemia.

PMID- 29015197
TI  - Observations on the Use of Myanesin as an Anticonvulsant in Tetanus.

PMID- 29015199
TI  - Studies on Blood Pressure, Height, Weight, Chest and Abdominal Measurements of
      2,500 Members of the Calcutta Police with Short Notes on Their Medical
      Impairments.

PMID- 29015200
TI  - Diagnostic Fluoroscopy and Its Position in Tuberculosis Case-Finding. (A Summary
      of Prevailing Views.).

PMID- 29015201
TI  - Serological Technique: Technique of Testing Blood with Human Testing Sera.
      Addendum.

PMID- 29015202
TI  - Erratum: Two Atypical Cases of Giardia Infection.
AB  - [This corrects the article on p. 103 in vol. 84.].

PMID- 29015203
TI  - Centrifugal Agglutination for Diagnosis.

PMID- 29015204
TI  - A Case of Pyloric Obstruction.

PMID- 29015205
TI  - Medical Education.

PMID- 29015206
TI  - Medical Education.

PMID- 29015207
TI  - Further Education of Medical Licentiates.

PMID- 29015208
TI  - Fifty Years Ago.

PMID- 29015209
TI  - Service Notes.

PMID- 29015210
TI  - Points from Letters.

PMID- 29015211
TI  - Some Observations on Medical Education with Special Reference to Teaching of
      Pharmacology and Therapeutics.

PMID- 29015212
TI  - Studies in the Bacterial AEtiology of Dental Caries.

PMID- 29015214
TI  - Medical Education.

PMID- 29015213
TI  - Medical Education.

PMID- 29015215
TI  - Medical News.

PMID- 29015217
TI  - Education of the Medical Licentiates.

PMID- 29015216
TI  - Leishmaniasis and the Sandfly.

PMID- 29015218
TI  - Laurence-Moon-Biedl Syndrome.

PMID- 29015219
TI  - Higher Medical Qualifications at Home.

PMID- 29015220
TI  - Current Topics, Etc.

PMID- 29015221
TI  - Abstracts from Reports.

PMID- 29015222
TI  - Chorea Following Benign Tertian Malaria.

PMID- 29015223
TI  - Contact Lenses.

PMID- 29015224
TI  - Myotonia Congenita. Thomsen's Disease.

PMID- 29015225
TI  - Medical Qualification and Registration.

PMID- 29015226
TI  - Abnormal Pectoralis Minor Muscle and Evidence of Modified Axillary Arch.

PMID- 29015227
TI  - Medical Education and Leprosy.

PMID- 29015228
TI  - The Relation of Refrigeration to Body-Weight.

PMID- 29015229
TI  - A Case of Full-Term Abdominal Pregnancy.

PMID- 29015230
TI  - Fifty Years Ago.

PMID- 29015231
TI  - Oath of Hippocrates.

PMID- 29015233
TI  - Blood Donation.

PMID- 29015232
TI  - Serological Technique (Contd.).

PMID- 29015234
TI  - Current Topics.

PMID- 29015235
TI  - Medical News.

PMID- 29015236
TI  - Abstracts from Reports.

PMID- 29015237
TI  - Service Notes.

PMID- 29015238
TI  - Helminthagogues.

PMID- 29015239
TI  - Reunion Dinner.

PMID- 29015240
TI  - Note on Industrial Canteens in Central Provinces.

PMID- 29015242
TI  - Venereal Diseases Number.

PMID- 29015241
TI  - Is Second Attack of Diphtheria Possible?

PMID- 29015243
TI  - Any Questions.

PMID- 29015244
TI  - Medical Men in India: Too Few or Too Many.

PMID- 29015245
TI  - Service Notes.

PMID- 29015247
TI  - Fifty Years Ago.

PMID- 29015246
TI  - Progressive Muscular Atrophy.

PMID- 29015248
TI  - Abstracts from Reports.

PMID- 29015249
TI  - Asthma and Pneumonia.

PMID- 29015250
TI  - Medical News.

PMID- 29015251
TI  - Antibiotics.

PMID- 29015252
TI  - Venereal Diseases Number.

PMID- 29015253
TI  - Infamous Conduct in a Professional Respect. Epstein v. Medical Board of Victoria.

PMID- 29015255
TI  - Dying Declaration. Rex v. Ivan Manfred Kahu.

PMID- 29015254
TI  - Current Topics.

PMID- 29015257
TI  - Compensation Court. Rowbottom v. Shaw, Savill and Albion Company Limited.
      Coronary Disease and Myocardial Infarction.

PMID- 29015256
TI  - Erratum.
AB  - [This corrects the article on p. 433 in vol. 81.].

PMID- 29015258
TI  - Fifty Years Ago.

PMID- 29015259
TI  - Service Notes.

PMID- 29015260
TI  - Abstracts from Reports.

PMID- 29015261
TI  - Medical News.

PMID- 29015263
TI  - Service Notes.

PMID- 29015262
TI  - Any Questions.

PMID- 29015264
TI  - Any Questions.

PMID- 29015265
TI  - Current Topics.

PMID- 29015267
TI  - Any Questions.

PMID- 29015266
TI  - Toxic Symptoms Associated with Quinacrine Treatment.

PMID- 29015268
TI  - Service Notes.

PMID- 29015269
TI  - A Case of Craniocleido-Dysostosis.

PMID- 29015270
TI  - Serological Technique (Contd.).

PMID- 29015271
TI  - The Use of Ground-Nut Cake Flour for Human Consumption.

PMID- 29015273
TI  - Treatment of Osteoarthritis with Intra-Articular Injections of Lactic Acid.

PMID- 29015272
TI  - Investigation on a Case of Feminism.

PMID- 29015274
TI  - History of Kala-Azar in India.

PMID- 29015275
TI  - Mepacrine Psychosis.

PMID- 29015276
TI  - Preliminary Report on a New Synthetic Antimalarial.

PMID- 29015277
TI  - Cerebral Malaria in Pregnancy Simulating Acute Yellow Atrophy of the Liver.

PMID- 29015279
TI  - A Typical Case of Iso-Immunization against the Rhesus Factor.

PMID- 29015278
TI  - Medical Treatment of Intestinal Obstruction.

PMID- 29015280
TI  - Medical News.

PMID- 29015281
TI  - Clinical Trials of Paludrine.

PMID- 29015282
TI  - A Clinical Study on Paludrine.

PMID- 29015283
TI  - Notes on Some Remedies IX. Amoebicides.

PMID- 29015284
TI  - Current Topics, Etc.

PMID- 29015285
TI  - A Case of Renal Glycosuria Associated with Hypovitaminosis C.

PMID- 29015286
TI  - Fifty Years Ago.

PMID- 29015288
TI  - Abstracts from Reports.

PMID- 29015287
TI  - Clinical Trial of Paludrine in Malaria.

PMID- 29015289
TI  - Homo Sapiens.

PMID- 29015290
TI  - A Case of Primary Pneumonic Plague.

PMID- 29015292
TI  - A Specially Esteemed Contributor.

PMID- 29015291
TI  - Fifty Years Ago.

PMID- 29015294
TI  - Cirrhosis of the Liver in the Adult.

PMID- 29015293
TI  - The Erythrocyte Sedimentation Rate in Rheumatic Fever and Other Conditions.

PMID- 29015295
TI  - Sodium Thiosulphate as an Antidote in Penicillin Exfoliative Dermatitis.

PMID- 29015296
TI  - A Case of Richter's Hernia Strangulated in the First Descent in a Congenital
      Right Inguinal Hernial Sac.

PMID- 29015298
TI  - Current Topics, Etc.

PMID- 29015297
TI  - The Present Position of Antimony Treatment of Filariasis: With a Suggestion for
      Its Intensive Use.

PMID- 29015300
TI  - Leukaemia and War Service.

PMID- 29015299
TI  - Small, Faint and Hidden Bloodstains.

PMID- 29015301
TI  - Service Notes.

PMID- 29015302
TI  - The Twin Dominions and the Indian Medical Gazette.

PMID- 29015303
TI  - The Effect of Processing and Souring Milk by the Indigenous Method.

PMID- 29015305
TI  - Abstracts from Reports.

PMID- 29015304
TI  - Inadequacy of Medical Education in India.

PMID- 29015306
TI  - The Value of Transfusion of Blood in the Treatment of Anaemias.

PMID- 29015307
TI  - Treatment of Typhoid Fever with Penicillin.

PMID- 29015308
TI  - Kala-Azar in Jaipur.

PMID- 29015309
TI  - Isolation of OEstrone from the Urine of a Case of Feminism.

PMID- 29015310
TI  - Brenner Tumour of the Ovary: Report of Two Cases, One in the Wall of a Serous
      Cystadenoma.

PMID- 29015311
TI  - Scrub Typhus in North Burma.

PMID- 29015312
TI  - Medical News.

PMID- 29015313
TI  - Any Questions.

PMID- 29015314
TI  - Inclusion Bodies in Rickettsia Orientalis Infection.

PMID- 29015315
TI  - Primary Atypical Pneumonia.

PMID- 29015316
TI  - Fifty Years Ago.

PMID- 29015317
TI  - Kala-Azar in India and the Sandfly.

PMID- 29015318
TI  - Erratum: Treatment of Epidemic Dropsy.
AB  - [This corrects the article on p. 165 in vol. 85.].

PMID- 29015319
TI  - Leprosy Tamed.

PMID- 29015321
TI  - Current Topics, Etc.

PMID- 29015320
TI  - Aureomycin in Kala-Azar.

PMID- 29015322
TI  - Medical News.

PMID- 29015323
TI  - Errata.
AB  - [This corrects the article on p. 373g in vol. 84.][This corrects the article on
      p. 373h in vol. 84.].

PMID- 29015324
TI  - Service Notes.

PMID- 29015325
TI  - Clinical Hydrophobia without Contact with Rabies Transmitting Animal.

PMID- 29015327
TI  - Medical News.

PMID- 29015326
TI  - Erratum: The Present Status of Sulphones in the Treatment of Leprosy.
AB  - [This corrects the article on p. 348 in vol. 85.].

PMID- 29015328
TI  - Fifty Years Ago.

PMID- 29015329
TI  - Parenteral Use of Vitamins.

PMID- 29015330
TI  - Current Topics, Etc.

PMID- 29015331
TI  - Any Questions.

PMID- 29015332
TI  - Current Topics, Etc.

PMID- 29015333
TI  - Fifty Years Ago.

PMID- 29015334
TI  - Service Notes.

PMID- 29015335
TI  - Medical News.

PMID- 29015336
TI  - Abstracts from Reports.

PMID- 29015337
TI  - Abreast with the Times.

PMID- 29015338
TI  - Correspondence.

PMID- 29015339
TI  - Correspondence.

PMID- 29015340
TI  - Mahatma Gandhi.

PMID- 29015341
TI  - The Irresistible Impulse.

PMID- 29015342
TI  - Deeds of Violence in India in 1935-36 and 1945-46, and Other Crimes in Which
      Serology Plays a Part.

PMID- 29015343
TI  - Prevention of Cruelty to Animals.

PMID- 29015345
TI  - Fifty Years Ago.

PMID- 29015344
TI  - Correspondence.

PMID- 29015346
TI  - The Supermen.

PMID- 29015348
TI  - The Death Penalty.

PMID- 29015347
TI  - Correspondence.

PMID- 29015349
TI  - Sacral Anaesthesia for Lower Abdominal and Perineal Surgery.

PMID- 29015350
TI  - Humane Slaughter of Animal.

PMID- 29015351
TI  - The Calcutta Deaf and Dumb School.

PMID- 29015352
TI  - Current Topics, Etc.

PMID- 29015353
TI  - Social Reform Section.

PMID- 29015354
TI  - Unwanted Medical Relief.

PMID- 29015355
TI  - Advantages of Regional Anaesthesia in Poor Surgical Risk Cases with Special
      Reference to Refrigeration Method. (A Report of 16 Poor Risk Cases.).

PMID- 29015356
TI  - Power Unlimited.

PMID- 29015357
TI  - Medical Education.

PMID- 29015358
TI  - Medical News.

PMID- 29015359
TI  - Erratum: The cc., c.cm., MIL., mil., and ml.
AB  - [This corrects the article on p. 281 in vol. 83.].

PMID- 29015361
TI  - What Should the General Practitioner Know about Filariasis.

PMID- 29015360
TI  - Euthanasia, Capital Punishment, Murder.

PMID- 29015362
TI  - Any Questions.

PMID- 29015363
TI  - A Large Pheochromocytoma of the Adrenal Gland.

PMID- 29015364
TI  - A Case of H. Influenzae Meningitis Treated with Penicillin and Sulphadiazine.

PMID- 29015365
TI  - Medical News.

PMID- 29015366
TI  - Observations of Ascorbic Acid. Part XI. Therapeutic Effect of Ascorbic Acid in
      Tuberculosis.

PMID- 29015367
TI  - Erratum: The Tragedy of Tragedies.
AB  - [This corrects the article on p. 331 in vol. 83.].

PMID- 29015368
TI  - Plasma Proteins in Peptic Ulcer.

PMID- 29015370
TI  - Erratum: Unwanted Medical Relief.
AB  - [This corrects the article on p. 320 in vol. 83.].

PMID- 29015369
TI  - An Unusual Case of Actinomycosis of Cheek.

PMID- 29015371
TI  - Current Topics, Etc.

PMID- 29015372
TI  - Service Notes.

PMID- 29015374
TI  - Abstracts from Reports.

PMID- 29015375
TI  - A Double-Headed Monster.

PMID- 29015373
TI  - Vitamin-'A' Deficiency among a Group of South Indian College Students.

PMID- 29015376
TI  - A Case of Complete Detachment of the Heart.

PMID- 29015377
TI  - Serological Technique (Contd.).

PMID- 29015378
TI  - Occupational Diseases in Relation to the Manufacture of Dichromates: Their
      Prevention and Treatment.

PMID- 29015380
TI  - Comatose Condition Due to B.T. Infection.

PMID- 29015379
TI  - Cerebral Symptoms in Benign Tertian Infection.

PMID- 29015381
TI  - Geneculate Herpes or 'Ramsay Hunt Syndrome'.

PMID- 29015384
TI  - Notes on Some Remedies. XXIII. Blood Transfusion, Part II.

PMID- 29015382
TI  - The Action of Shiga Toxins on Laboratory Animals in General and on Monkeys in
      Particular.

PMID- 29015383
TI  - Pneumonic Plague and Its Treatment.

PMID- 29015386
TI  - Fifty Years Ago.

PMID- 29015385
TI  - Two Cases of Tropical Eosinophilia in Tea Estate Practice.

PMID- 29015387
TI  - Observations on Pneumococcal Meningitis as a Complication of Kala-Azar.

PMID- 29015389
TI  - Service Notes.

PMID- 29015388
TI  - The Shortage of Food and Cloth.

PMID- 29015390
TI  - A Report of 46 Cases of Anaemia in the Punjab with Special Reference to
      Nutritional Macrocytic and Addisonian Anaemia.

PMID- 29015391
TI  - The Incidence and Causation of Glycosuria in Pregnancy. Part III.

PMID- 29015392
TI  - An Analysis of 50,000 Skin Cases as Seen in the Out-Patient Department of the
      School of Tropical Medicine, Calcutta, during the Five Years from 1942 to 1946.

PMID- 29015394
TI  - Any Questions.

PMID- 29015393
TI  - Incidence of Frontal or Metopic Suture Amongst Punjabee Adults.

PMID- 29015395
TI  - Fifty Years Ago.

PMID- 29015397
TI  - Chloromycetin.

PMID- 29015396
TI  - Serological Technique (Contd.).

PMID- 29015399
TI  - Current Topics, Etc.

PMID- 29015398
TI  - A Study on the Health Habits of a Rural Community in West Bengal in the Matter of
      Medical Relief with Special Reference to the Utilization of Free Medical Service.

PMID- 29015400
TI  - Medical News.

PMID- 29015401
TI  - Fifty Years Ago.

PMID- 29015403
TI  - Polio: Two New Points.

PMID- 29015402
TI  - Treatment of Typhoid Fever with Bacteriophage.

PMID- 29015404
TI  - Abstracts from Reports.

PMID- 29015405
TI  - Current Topics, Etc.

PMID- 29015406
TI  - Aureomycin in Tropical Eosinophilia.

PMID- 29015408
TI  - Points from a Letter.

PMID- 29015407
TI  - Treatment of Cholera.

PMID- 29015409
TI  - Medical News.

PMID- 29015410
TI  - Sudden Heart Failure.

PMID- 29015411
TI  - Current Topics, Etc.

PMID- 29015412
TI  - Correspondence.

PMID- 29015413
TI  - Abstracts from Reports.

PMID- 29015414
TI  - Sulphonamides and Sulphones.

PMID- 29015416
TI  - Medical News.

PMID- 29015415
TI  - Treatment of Infantile Cirrhosis of the Liver.

PMID- 29015417
TI  - Kala-Azar in India and the Sandfly.

PMID- 29015418
TI  - Paludrine Poisoning.

PMID- 29015419
TI  - Sulpha and Sulphone Drugs.

PMID- 29015420
TI  - The Treponematoses.

PMID- 29015421
TI  - Fifty Years Ago.

PMID- 29015422
TI  - Acute Paludrine Poisoning.

PMID- 29015423
TI  - Report on the Epidemic of Anterior Poliomyelitis in the Nicobar Islands.

PMID- 29015424
TI  - Cases of Sprue Treated by Laparotomy.

PMID- 29015425
TI  - A Case of Plastic Bronchitis.

PMID- 29015426
TI  - A New Operation for Entropion and Trichiasis of the Upper Eyelids.

PMID- 29015428
TI  - Homicide and Capital Punishment.

PMID- 29015427
TI  - Lymphadenoma of the Salivary Glands.

PMID- 29015429
TI  - Erratum: A Simple Method of Cutting Serial Sections of Ticks.
AB  - [This corrects the article on p. 181 in vol. 83.].

PMID- 29015430
TI  - Sebaceous Horn Penis.

PMID- 29015431
TI  - A Case of Bacteraemia Caused by Bacterium Alkaligenes Faecalis.

PMID- 29015432
TI  - Fifty Years Ago.

PMID- 29015433
TI  - Serological Technique (Contd.).

PMID- 29015434
TI  - Corneal Opacities among Children of a Railway Colony in the Dekkan.

PMID- 29015435
TI  - Service Notes.

PMID- 29015436
TI  - Any Questions.

PMID- 29015437
TI  - Extrapleural Plombage with Lucite Spheres.

PMID- 29015438
TI  - Anti-Tuberculosis Measures by South African Indians.

PMID- 29015439
TI  - Between Ourselves on Preparing a Theme.

PMID- 29015440
TI  - Notes on Some Remedies. XXII. Blood Transfusion, Part I.

PMID- 29015441
TI  - Three Cases of Iso-Immunization against Rh Antigen Found in Five Weeks in
      Calcutta and Associated Considerations.

PMID- 29015442
TI  - Medical News.

PMID- 29015443
TI  - Aneurysm of Thoracic Aorta.

PMID- 29015444
TI  - Current Topics, Etc.

PMID- 29015445
TI  - Current Topics, Etc.

PMID- 29015446
TI  - Generalized Cysticercosis Cellulosae.

PMID- 29015448
TI  - Any Questions.

PMID- 29015447
TI  - Advertisements in Medical Journals.

PMID- 29015450
TI  - Medical News.

PMID- 29015449
TI  - Erratum.
AB  - [This corrects the article on p. 272 in vol. 85.].

PMID- 29015451
TI  - Fifty Years Ago.

PMID- 29015452
TI  - Abstracts from Reports.

PMID- 29015454
TI  - Paludrine Poisoning.

PMID- 29015453
TI  - Paludrine Poisoning.

PMID- 29015455
TI  - Medical Councils.

PMID- 29015456
TI  - Service Notes.

PMID- 29015457
TI  - Allergy: Newer Knowledge.

PMID- 29015458
TI  - Medical News.

PMID- 29015459
TI  - The King's Health.

PMID- 29015460
TI  - Current Topics, Etc.

PMID- 29015462
TI  - Fifty Years Ago.

PMID- 29015461
TI  - Trial of Streptomycin in Plague.

PMID- 29015463
TI  - A Case of Hyperplastic Ileocaecal Tuberculosis Treated with Pneumoperitoneum.

PMID- 29015464
TI  - M. T. Malaria Simulating Acute Abdomen.

PMID- 29015465
TI  - Glucose Injection.

PMID- 29015466
TI  - The Experience of 'Air Embolism-Pleural Shock during Artificial Pneumothorax in
      Pulmonary Tuberculosis Cases'.

PMID- 29015468
TI  - By Gum They Are Stuck.

PMID- 29015467
TI  - Medical Books.

PMID- 29015469
TI  - Effect of Penicillin on Vaccine Virus and Its Value in Purification of Vaccine
      Lymph.

PMID- 29015470
TI  - Lipomas, Big and Small.

PMID- 29015471
TI  - Notes on Some Remedies. XXIV. Blood Transfusion. Part III.

PMID- 29015473
TI  - Service Notes.

PMID- 29015472
TI  - Abstracts from Reports.

PMID- 29015475
TI  - Medical News.

PMID- 29015474
TI  - The Place of Vasectomy in Leprosy Control.

PMID- 29015476
TI  - Serological Technique(Contd.).

PMID- 29015477
TI  - Higher Medical Qualifications at Home.

PMID- 29015478
TI  - Treatment of Paralytic Ileus.

PMID- 29015479
TI  - Selection of Medical Teachers.

PMID- 29015481
TI  - Current Topics, Etc.

PMID- 29015480
TI  - Further Observations on Parenteral Paludrine Hydrochloride in Malarial Fevers.

PMID- 29015482
TI  - Any Questions.

PMID- 29015483
TI  - Leprosy Sufferers Need 'New Deal'.

PMID- 29015484
TI  - Fifty Years Ago.

PMID- 29015486
TI  - Industrial Medicine.

PMID- 29015485
TI  - Thrombo-Angiitis Obliterans Treated by Bilateral Lumbar Sympathectomy.

PMID- 29015487
TI  - Seventy Five Years Ago.

PMID- 29015488
TI  - Comparative Studies of Liver Function Tests in Infective Hepatitis.

PMID- 29015489
TI  - Erratum: Serological Classification of C. Diphtheriae in Calcutta.
AB  - [This corrects the article on p. 28 in vol. 89.].

PMID- 29015490
TI  - Chronic Brucellosis.

PMID- 29015491
TI  - Erratum: Scrub Typhus in the Karnal District of Punjab (India).
AB  - [This corrects the article on p. 621 in vol. 88.].

PMID- 29015492
TI  - Fifty Years Ago.

PMID- 29015493
TI  - A Comparative Study of Phthalylsulphathiazol, Chloromycetin and Aureomycin in the
      Treatment of Cholera.

PMID- 29015494
TI  - Unusual Foreign Body in Abdomen.

PMID- 29015495
TI  - Post-Operative Appraisal of 1100 Surgical Cases.

PMID- 29015497
TI  - The Radio Active Ash.

PMID- 29015496
TI  - Mair's Dermatoplasty.

PMID- 29015498
TI  - Twenty Five Years Ago.

PMID- 29015499
TI  - Anthropometry and Blood Pressure of 6,000 Bihari Officers and Men of the West
      Bengal, Calcutta and Bihar Police Forces and West Bengal Fire Services.

PMID- 29015501
TI  - Current Topics, Etc.

PMID- 29015500
TI  - Medical News.

PMID- 29015502
TI  - X-Ray Appearances in the Lung Fields in Tropical Eosinophilia.

PMID- 29015503
TI  - Erratum: Murine Typhus in Karnal City.
AB  - [This corrects the article on p. 623 in vol. 88.].

PMID- 29015504
TI  - Idiopathic Volvulus and Intussusception of the Turminal Ileum in the Adult.

PMID- 29015505
TI  - Tuberculosis of the Skin-Assessment of Clinical and Histological Changes
      Following Isonicotinic Acid Hydrazide Therapy.

PMID- 29015506
TI  - Indigenous Drugs in Experimental Diabetes.

PMID- 29015508
TI  - Seventy Five Years Ago.

PMID- 29015507
TI  - Growth and Survival of Cholera Vibrio in Relation to pH.

PMID- 29015510
TI  - Fifty Years Ago.

PMID- 29015509
TI  - A Case of Typhus in Rupar.

PMID- 29015511
TI  - Medical News.

PMID- 29015512
TI  - Recent Antimalarials in Giardiasis.

PMID- 29015513
TI  - Malignant Melanoma in the Nose (A Case Report).

PMID- 29015514
TI  - Relapses in Cerebral Malaria (Case Report).

PMID- 29015515
TI  - A Report on Two Further Cases of Encysted Guinea Worm Abscess.

PMID- 29015516
TI  - Current Topics, Etc.

PMID- 29015517
TI  - Twenty Five Years Ago.

PMID- 29015519
TI  - The Elusive Water Vibrio.

PMID- 29015518
TI  - Tropical Liver Abscess Affecting the Left Lobe.

PMID- 29015520
TI  - Institute of Child Health Trust.

PMID- 29015522
TI  - Seventy Five Years Ago.

PMID- 29015521
TI  - A Case of Typhoid Meningitis-Treated with Chloromycetin.

PMID- 29015523
TI  - Family Planning Work in Lucknow.

PMID- 29015524
TI  - Twenty Five Years Ago.

PMID- 29015525
TI  - A Case of Unusual Genital Malformation.

PMID- 29015526
TI  - Current Topics, Etc.

PMID- 29015527
TI  - Fifty Years Ago.

PMID- 29015528
TI  - An Experimental Study of Tromexan.

PMID- 29015529
TI  - Cat Scratch Disease (with a Case Report).

PMID- 29015531
TI  - Ovarian Tumour with Masculinizing Syndrome.

PMID- 29015530
TI  - Physiological Action of 'Resodec', a Cationic Exchange Synthetic Resin.

PMID- 29015532
TI  - Erratum: Kertoderma Blenorrhagica.
AB  - [This corrects the article on p. 157 in vol. 88.].

PMID- 29015533
TI  - Erratum: The Wassermann Reaction in the Tropics.
AB  - [This corrects the article on p. 196 in vol. 88.].

PMID- 29015534
TI  - Science Conference.

PMID- 29015535
TI  - Imperforate Anus, Rectovaginal and Rectovesical Fistulae.

PMID- 29015536
TI  - A Field Survey of Fasciolopsis Buski in Chandra in Area of Saharsa District
      (Bihar).

PMID- 29015537
TI  - Errata.
AB  - [This corrects the article on p. 33 in vol. 89.].

PMID- 29015538
TI  - Medical News.

PMID- 29015539
TI  - Effect of Argemone Oil on Monkeys.

PMID- 29015540
TI  - Medical News.

PMID- 29015541
TI  - A Note on Vibrios Isolated in Kumbh Fair, Allahabad, 1954.

PMID- 29015542
TI  - Old Tales Retold: With Fresh Comments.

PMID- 29015543
TI  - Current Topics.

PMID- 29015544
TI  - The Kumph without Cholera: A Great Achievement.

PMID- 29015545
TI  - Twenty Five Years Ago.

PMID- 29015546
TI  - Idiopathic Pleuricy with Effusion and Its Sequelae.

PMID- 29015547
TI  - The Treatment of Pulmonary Tuberculosis, T. B. Meningitis and T. B. Pericarditis
      with the Combination of Isonicotinic Acid Hydrazide and Streptomycin.

PMID- 29015549
TI  - Seventy Five Years Ago.

PMID- 29015548
TI  - Antihistamimics in Cholera (A Reply).

PMID- 29015551
TI  - Radio Active Ash: A Portscript.

PMID- 29015550
TI  - Fifty Years Ago.

PMID- 29015552
TI  - A Report on the Isolation of Two Strains of Influenza B Virus in India.

PMID- 29015553
TI  - Convocation Address at the College of Physicians and Surgeons of Bombay.

PMID- 29015554
TI  - Sciatica and Brachial Neuritis as Complications of Brucellosis.

PMID- 29015555
TI  - Errata.
AB  - [This corrects the article on p. 122 in vol. 89.].

PMID- 29015556
TI  - Seventy-Five Years Ago.

PMID- 29015557
TI  - Influence of Pyridoxine on Fat Metabolism in Phrynoderma.

PMID- 29015558
TI  - Brucellosis.

PMID- 29015560
TI  - Observation on BCG Vaccination of Nurses.

PMID- 29015559
TI  - Activities of Alkaline Phosphatase in Health and Disease: A Review of 185
      Hospital Cases.

PMID- 29015561
TI  - Twenty Five Years Ago.

PMID- 29015562
TI  - Erratum: Mair's Dermatoplasty.
AB  - [This corrects the article on p. 221 in vol. 89.].

PMID- 29015563
TI  - Current Topics, Etc.

PMID- 29015564
TI  - Drug Analysts' Conference.

PMID- 29015565
TI  - Errata.
AB  - [This corrects the article on p. 189 in vol. 89.].

PMID- 29015566
TI  - Vegetarians and Malnutrition.

PMID- 29015567
TI  - Infantile Scurvy in the Punjab.

PMID- 29015568
TI  - Fifty Years Ago.

PMID- 29015569
TI  - Medical News.

PMID- 29015572
TI  - Twenty Five Years Ago.

PMID- 29015571
TI  - The Present Status of Dish Washing Procedures Adopted in Coffee Houses and
      Restaurants-A Bacteriological Assay.

PMID- 29015573
TI  - Birth of Monster Babies in Succession.

PMID- 29015574
TI  - Histoplasmin, Coccidioidin, Blastomycin, Tuberculin Sensitivity in Relation to
      Tropical Eosinophilia and Pulmonary Calcifications.

PMID- 29015576
TI  - Current Topics, Etc.

PMID- 29015575
TI  - Low Blood Vitamin A Levels in Dermatology.

PMID- 29015577
TI  - Old Tales Retold with Fresh Comments.

PMID- 29015579
TI  - Serological Classification of C. Diphtheriae in Calcutta.

PMID- 29015578
TI  - Clinical Observations with New Amoebicidal Drugs Part I: Trials with Resotren.

PMID- 29015580
TI  - Seventy Five Years Ago.

PMID- 29015581
TI  - Fifty Years Ago.

PMID- 29015582
TI  - Medical News.

PMID- 29015585
TI  - Comparative Study of the Treatment of Tuberculous Cervical Lymphadenitis with
      Special Reference of Streptomycin, P.A.S. and Isonicotinic Acid Hydrazide.

PMID- 29015584
TI  - Primary Carcinoma of the Liver.

PMID- 29015583
TI  - Streptomycin and Terramycin in the Treatment of Rat-Bite Fever Due to Spirillum
      Minus.

PMID- 29015587
TI  - Twenty Five Years Ago.

PMID- 29015586
TI  - High Vitamin a Levels in the Blood Serum in Certain Skin Diseases.

PMID- 29015588
TI  - Seventy Five Years Ago.

PMID- 29015589
TI  - Current Topics, Etc.

PMID- 29015590
TI  - Murine Typhus in Karnal City.

PMID- 29015591
TI  - Scrub Typhus in the Kanal District of Punjab (India).

PMID- 29015592
TI  - Fireside Fantasies.

PMID- 29015593
TI  - Analysis of Some Cooked Diets (Bengali).

PMID- 29015594
TI  - Fifty Years Ago.

PMID- 29015595
TI  - The Piltdown Man.

PMID- 29015597
TI  - Cor Pulmonale.

PMID- 29015596
TI  - Medical News.

PMID- 29015598
TI  - Guillain-Barre Syndrome with a Case Report.

PMID- 29015599
TI  - Cavernous Angioma Arising from Male Breast.

PMID- 29015600
TI  - The RH Subgroups in South Indians.

PMID- 29015601
TI  - Current Topics, Etc.

PMID- 29015602
TI  - Pulmonary Heart Disease with an Account of a Case.

PMID- 29015603
TI  - Medical News.

PMID- 29015605
TI  - Fifty Years Ago.

PMID- 29015604
TI  - Comparative Studies of Liver Function Tests in Portal Cirrhosis.

PMID- 29015606
TI  - Studies on Metabolism of Calcium, Inorganic Phosphorus and Cholesterol in
      Pregnancy with Helminthic Infection in Indian Women.

PMID- 29015607
TI  - Thoracoscopy and Intrapleural Pheumonolysis: Analysis of 354 Cases.

PMID- 29015608
TI  - Utilisation of Indian Dioxorea Plants for Preparation of Cortisone.

PMID- 29015609
TI  - General Instruction for Civil Hospital Diets.

PMID- 29015611
TI  - Medical News.

PMID- 29015610
TI  - The Diagnostic Significance of Tremors.

PMID- 29015612
TI  - Erythrocyte Sedimentation Rate in Health and Disease.

PMID- 29015613
TI  - Encephalitis: A Report of Eleven Cases.

PMID- 29015614
TI  - Effect of Methylxanthines on Blood Coagulation.

PMID- 29015615
TI  - Nutritional Peripheral Neuropathy Related to "The Shoulder Girdle Syndrome" in
      Persia and Iraq Force 1944-45 Part II.

PMID- 29015616
TI  - Fifty Years Ago.

PMID- 29015617
TI  - Chloramphenicol in Early Diagnosis of Typhoid.

PMID- 29015618
TI  - First World Conference on Medical Education.

PMID- 29015619
TI  - Erratum: Abstract with the Times Again.
AB  - [This corrects the article on p. 535 in vol. 88.].

PMID- 29015620
TI  - C. S. F. in 105 Cases.

PMID- 29015622
TI  - Current Topics, Etc.

PMID- 29015621
TI  - Intestinal Thiamine Synthesis as Influenced by Different Fats.

PMID- 29015623
TI  - Seventy-Five Years Ago.

PMID- 29015624
TI  - Twenty-Five Years Ago.

PMID- 29015625
TI  - Sturge-Weber Syndrome (with an Illustrative Case Report).

PMID- 29015626
TI  - Acute Dilatation of Stomach during Operation for Gastric Carcinoma.

PMID- 29015627
TI  - WHO Press Release.

PMID- 29015629
TI  - Fifty Years Ago.

PMID- 29015628
TI  - Notes on Sand-Flies. Part V.

PMID- 29015631
TI  - Current Topics, Etc.

PMID- 29015630
TI  - An Analytical Study of Lymphadenopathy in Rajasthan. (160 Lymph Nodes).

PMID- 29015632
TI  - Isoncotinic Acid Hydrazide in the Treatment of Endometrial Tuberculosis.

PMID- 29015634
TI  - Epidemic Haemorrhagic Fever of Korea.

PMID- 29015633
TI  - Intussusception: Report of a Case in Adult Due to a Polyp in Small Intestine.

PMID- 29015636
TI  - Medical News.

PMID- 29015635
TI  - Nutritional Oedema and Consumption Level in Yet Another Food Scarcity Area of
      Bihar.

PMID- 29015637
TI  - Neuromyelitis Optica.

PMID- 29015638
TI  - Nutritional Peripheral Neuropathy Related to "The Shoulder Girdle Syndrome" in
      Persia and Iraq Force 1944-45.

PMID- 29015639
TI  - Protozoal Development and Natural Purification of Flowing Sewage.

PMID- 29015640
TI  - Current Topics, Etc.

PMID- 29015641
TI  - Fifty Years Ago.

PMID- 29015642
TI  - Medical News.

PMID- 29015643
TI  - Unusual Symptoms in Plasmodium Vivax Infection.

PMID- 29015644
TI  - Vitamin C and Antihistaminics in the Treatment of Uraemia in Cholera.

PMID- 29015645
TI  - Serum Calcium and Phosphorus, 24 Hours after Massive Calciferol Therapy.

PMID- 29015646
TI  - The Treatment of Malaria with Resochin.

PMID- 29015647
TI  - Epidemiology of XK Typhus in Jamshedpur.

PMID- 29015649
TI  - Abreast with the Times Again.

PMID- 29015648
TI  - Trichophyton Purpureum Infection in India.

PMID- 29015650
TI  - Treatment of Abdominal Tuberculosis with PAS.

PMID- 29015651
TI  - A Case of Central Placenta Praevia with Natural Spontaneous Delivery.

PMID- 29015652
TI  - Wassermann Reaction and Slide Modification of Meinicke's Test-A Comparative Study
      on 10,193 Sera.

PMID- 29015653
TI  - A Case of Acute Lymphatic Leukaemia in an Adult Treated with Antifolic Acid
      Substance.

PMID- 29015654
TI  - Dietary Habits of School Boys in Uttar Pradesh.

PMID- 29015655
TI  - Notes on Sand-Flies: Part IV-Some Important Variations in the Morphology of
      Phlebotomus Argentipes Found in Poona.

PMID- 29015657
TI  - Fifty Years Ago.

PMID- 29015656
TI  - Health Conditions of the Seamen at the Port of Calcutta: A Preliminary Report.

PMID- 29015658
TI  - Thromboangiitis Obliterans.

PMID- 29015659
TI  - Current Topics, Etc.

PMID- 29015660
TI  - Studies on Metabolism of Calcium, Inorganic Phosphorus and Cholesterol in Pre
      Eclamptic Toxaemias of Pregnancy.

PMID- 29015661
TI  - Use of DDT for the Control of Cyclops Breeding and as an Antidracontiasis
      Measure.

PMID- 29015663
TI  - Medical News.

PMID- 29015662
TI  - Chronic Encysted Guinea-Worm Lesion.

PMID- 29015665
TI  - Medical News.

PMID- 29015664
TI  - Terramycin as a Therapeutic Agent against Mumps.

PMID- 29015666
TI  - Free Visits.

PMID- 29015667
TI  - U. K. Flood-Relief Supplies to India.

PMID- 29015668
TI  - Four Lakh Workers to Benefit Free Medical Care through Panel Doctors.

PMID- 29015669
TI  - U.K. Offers Milk to Overseas Dependencies.

PMID- 29015671
TI  - On Divali Night.

PMID- 29015670
TI  - Brightening of Homes in the Tropics: Interior Colour Wash.

PMID- 29015672
TI  - A System of Automassage.

PMID- 29015673
TI  - Aiding Asian Students' Welfare.

PMID- 29015674
TI  - Co-Existence of Pulmonary and Cutaneous Tuberculosis.

PMID- 29015675
TI  - Tuberculous Meningitis Domiciling Treatment Non Possible.

PMID- 29015676
TI  - Sickness Benefit.

PMID- 29015677
TI  - Fat People Lose Weight Communally.

PMID- 29015678
TI  - Prehistoric Cockroach Is Modern Pest.

PMID- 29015679
TI  - Benefits in Cash.

PMID- 29015680
TI  - Generous Pensions.

PMID- 29015681
TI  - Seventy Five Years Ago.

PMID- 29015683
TI  - Regional Organisations.

PMID- 29015682
TI  - Dichroa Febrifuga and a Synthetic Hydrangea Alkaloid in Malaria.

PMID- 29015684
TI  - An Unusual Case of Aneurysm of the Sinus of Valsalva Dissecting into the
      Ventricular Septum and the Left Auricle.

PMID- 29015685
TI  - Twenty Five Years Ago.

PMID- 29015686
TI  - A Case of Mysophobia.

PMID- 29015688
TI  - Current Topics, Etc.

PMID- 29015687
TI  - Erratum: An Erratum.
AB  - [This corrects the article on p. 431 in vol. 89.].

PMID- 29015689
TI  - Fifty Years Ago.

PMID- 29015690
TI  - Benign Lymphogranulomatosis.

PMID- 29015691
TI  - Projects in India.

PMID- 29015692
TI  - Free Medical Care.

PMID- 29015694
TI  - Errors in Dispensing Due to Confusion of Weights.

PMID- 29015693
TI  - Transmission of Kala-Azar in India.

PMID- 29015695
TI  - Current Topics.

PMID- 29015696
TI  - The Sulphonamides in Bacillary Dysentery.

PMID- 29015697
TI  - Wound Shock.

PMID- 29015698
TI  - Service Notes.

PMID- 29015699
TI  - Some Observations on Fly Breeding in Compost Trenches.

PMID- 29015700
TI  - Erratum: Weight, Height and Chest Measurements, etc.
AB  - [This corrects the article on p. 301 in vol. 80.].

PMID- 29015701
TI  - The Control of Acute Bacterial Respiratory Diseases by Sulpha-Drugs.

PMID- 29015702
TI  - Abstracts from Reports.

PMID- 29015703
TI  - Endemic Fluorosis in Western Kweichow.

PMID- 29015704
TI  - Medical News.

PMID- 29015705
TI  - Congenital Absence of the Shaft of the Femur on Both Sides.

PMID- 29015706
TI  - Non-Traumatic Rupture of the Spleen: With a Case Report.

PMID- 29015707
TI  - Prevention of Smallpox by Vaccination and Revaccination: A Critical Study.

PMID- 29015709
TI  - Scabies in Bengal.

PMID- 29015708
TI  - Sulphanilyl Benzamide in the Treatment of Bacillary Dysentery.

PMID- 29015710
TI  - A Clinical Study of 89 Cases of Encephalitis.

PMID- 29015711
TI  - A Patient with Many Diseases.

PMID- 29015712
TI  - Sulphanilylguanidine in Cholera.

PMID- 29015715
TI  - Sulphanilamide in Acute Nephritis: A Study of 22 Cases.

PMID- 29015714
TI  - Treatment of Cerebro-Spinal Fever with Sulphapyridine : Observations on 464
      Cases.

PMID- 29015713
TI  - A Note on the Presence of 'O' Agglutinins in the Blood of Cholera Patients.

PMID- 29015716
TI  - Hypodermic Solution of Sulphate of Quinine.

PMID- 29015717
TI  - Atypical Malarial Gametocytes in the Peripheral Blood.

PMID- 29015718
TI  - The Action of Drugs on Dysentery Bacteriophage.

PMID- 29015720
TI  - Service Notes.

PMID- 29015719
TI  - Guinea-Pig Inoculation in the Diagnosis of Tuberculosis.

PMID- 29015721
TI  - Rural Medical Relief.

PMID- 29015723
TI  - Science and India.

PMID- 29015722
TI  - Weight, Height and Chest Measurements in Classification of Types of Individuals.

PMID- 29015724
TI  - Corrigendum.
AB  - [This corrects the article on p. 157 in vol. 80.].

PMID- 29015725
TI  - Abstracts from Reports.

PMID- 29015726
TI  - Medical News.

PMID- 29015727
TI  - A Case Illustrating the Association between Chicken-Pox and Herpes Zoster.

PMID- 29015729
TI  - Current Topics.

PMID- 29015728
TI  - A Case of Fracture of the Base of Skull Resulting in Blindness.

PMID- 29015730
TI  - Control of Fly-Breeding in Compost Heaps.

PMID- 29015731
TI  - Erratum: Serum Transfusions in Air-Raid Casualties in South-East Bengal.
AB  - [This corrects the article on p. 611 in vol. 79.].

PMID- 29015732
TI  - Corrigendum.
AB  - [This corrects the article on p. 132 in vol. 80.].

PMID- 29015733
TI  - Debridement.

PMID- 29015735
TI  - Pseudo-Paralysis Due to Scorbutic Epiphysitis.

PMID- 29015734
TI  - The Immediate Need of Reform of the Medical Councils of India.

PMID- 29015736
TI  - M 3349 (Paludrine) in the Treatment of Human Malaria.

PMID- 29015737
TI  - Individual Variations in the Absorption of Drugs from the Gastrointestinal Tract.

PMID- 29015738
TI  - Some Observations on Krukenberg Tumour of Ovary.

PMID- 29015739
TI  - Service Notes.

PMID- 29015741
TI  - Medical News.

PMID- 29015740
TI  - Larvicidal Fish of Kangra Valley-Schizothorax Progastus.

PMID- 29015742
TI  - Abstracts from Reports.

PMID- 29015743
TI  - Fever in a Hyper-Endemic Malarial Area: A Critical Analysis of 2,913 Cases.

PMID- 29015744
TI  - The Copper-Sulphate Specific-Gravity Method of Blood Analysis.

PMID- 29015745
TI  - Organization of Traumatic Surgery.

PMID- 29015746
TI  - A Case of Post-Influenzal Granulocytopenia Treated with Liver.

PMID- 29015747
TI  - On the D.E.C. Medium of Panja and Ghosh.

PMID- 29015748
TI  - Ovarian Tumour in a Three-Year-Old Child.

PMID- 29015749
TI  - Cerebral Malaria.

PMID- 29015750
TI  - Current Topics.

PMID- 29015751
TI  - Effect of Penicillin on a Case of Ulcus Tropicum (Naga Sore).

PMID- 29015752
TI  - Persistent Intractable Headache in an Adult Caused by Ascaris Lumbricoides.

PMID- 29015753
TI  - Agranulocytosis.

PMID- 29015754
TI  - Rejected Articles.

PMID- 29015756
TI  - Current Topics.

PMID- 29015755
TI  - Treatment of Carbuncle with Penicillin.

PMID- 29015757
TI  - Service Notes.

PMID- 29015758
TI  - Abstracts from Reports.

PMID- 29015759
TI  - Burns and Scalds.

PMID- 29015760
TI  - Medical News.

PMID- 29015761
TI  - Medical News.

PMID- 29015762
TI  - Observations on Malaria and Other Conditions Seen in Burma Evacuees.

PMID- 29015763
TI  - Subacute Constrictive Pericarditis.

PMID- 29015764
TI  - Natarphal (C. Bonducella) in Malarial Fevers.

PMID- 29015765
TI  - A Case of Schistosomiasis Infection Contracted in India.

PMID- 29015766
TI  - Amoebiasis of the Anus and Perineum: With Report of a Case.

PMID- 29015767
TI  - Service Notes.

PMID- 29015768
TI  - Experimental Studies in Rat-Bite Fever.

PMID- 29015769
TI  - Voges-Proskauer Test with Leifson's Reagent.

PMID- 29015770
TI  - Penicillin in the Treatment of Wounds.

PMID- 29015771
TI  - Fulminating or Malignant Cerebrospinal Fever.

PMID- 29015772
TI  - A Case of Filariasis of the Eye.

PMID- 29015774
TI  - Current Topics.

PMID- 29015773
TI  - The Diagnosis of Early Gastric Cancer: With a Review of 60 Cases.

PMID- 29015775
TI  - Malaria Parasite Findings in Blood Films in Relation to Malaria Forecasts in
      Ceylon.

PMID- 29015776
TI  - The Distribution of Typhoid Vi Agglutinins in Normal Sera with Special Reference
      to Their Diagnostic Value in Typhoid Fever.

PMID- 29015777
TI  - Infectious Mononucleosis: Glandular Fever.

PMID- 29015778
TI  - Abstracts from Reports.

PMID- 29015780
TI  - Oriental Sore in the Nizam's Dominions: Some Epidemiological Factors.

PMID- 29015779
TI  - Nutritional Diarrhoea.

PMID- 29015781
TI  - 'Entero-Vioform' and 'Vioform'.

PMID- 29015782
TI  - Amoebiasis and Blackwater Fever.

PMID- 29015783
TI  - Coma Due to Malaria.

PMID- 29015784
TI  - Some Physical and Immunological Reactions of RBC 'Juice' and Stroma.

PMID- 29015786
TI  - Paludrine-M.4888.

PMID- 29015785
TI  - Weight, Height and Chest Measurements in the Classification of Types of
      Individuals.

PMID- 29015788
TI  - Service Notes.

PMID- 29015787
TI  - Malarial Infection in the New-Born.

PMID- 29015789
TI  - Medical News.

PMID- 29015790
TI  - Treatment of Cerebro-Spinal Fever with Sulphapyridine.

PMID- 29015791
TI  - Protein Hydrolysate in Infective Hepatitis.

PMID- 29015793
TI  - Papilloma of the Bladder in a Child Three Years Old.

PMID- 29015792
TI  - Paludrine-M.4888.

PMID- 29015795
TI  - Current Topics.

PMID- 29015794
TI  - Idiopathic Gangrene of the Scrotum.

PMID- 29015796
TI  - Abstracts from Reports.

PMID- 29015798
TI  - Beri-Beri: Adult and Infantile.

PMID- 29015797
TI  - Blood Staining for Malaria Parasites.

PMID- 29015799
TI  - The Intervertebral Disc and Sciatica.

PMID- 29015800
TI  - The Copper Sulphate Specific Gravity Method of Blood Analysis.

PMID- 29015801
TI  - Service Notes.

PMID- 29015802
TI  - Current Topics.

PMID- 29015803
TI  - Medical News.

PMID- 29015804
TI  - Toronto Unit.

PMID- 29015806
TI  - Abstracts from Reports.

PMID- 29015805
TI  - Prevention of Smallpox by Vaccination and Revaccination.

PMID- 29015808
TI  - Service Notes.

PMID- 29015807
TI  - Current Topics.

PMID- 29015809
TI  - Medical News.

PMID- 29015810
TI  - Medical News.

PMID- 29015811
TI  - Abstracts from Reports.

PMID- 29015812
TI  - Current Topics.

PMID- 29015813
TI  - Industrialization of India and Its Likely Effect on Tuberculosis Problems.

PMID- 29015814
TI  - The Fight against Tuberculosis in India: A New Weapon Needed.

PMID- 29015815
TI  - The Medical Profession in India and Its Education.

PMID- 29015816
TI  - The Planning of a Tuberculosis Survey to Determine the Morbidity Rate (With
      Special Reference to Indian Conditions).

PMID- 29015818
TI  - Service Notes.

PMID- 29015817
TI  - Lobectomy for Abscess of the Lung.

PMID- 29015819
TI  - A Study of Certain Factors Influencing Results of Artificial Pneumothorax
      Treatment.

PMID- 29015820
TI  - Corrigendum.
AB  - [This corrects the article on p. 607 in vol. 79.].

PMID- 29015821
TI  - Simultaneous Bilateral 'Early Infiltration' in a Middle-Aged Patient.

PMID- 29015822
TI  - Tropical Eosinophilia: A Report on Fifteen Cases.

PMID- 29015823
TI  - The Normal Movements of the Colon after Barium Meal in Indians and Europeans.

PMID- 29015824
TI  - Tropical Eosinophilia.

PMID- 29015825
TI  - University of Madras.

PMID- 29015826
TI  - An Anti-Tuberculosis Scheme for an Indian City.

PMID- 29015827
TI  - Carbohydrate Metabolism in the Different Pathological Types of Pulmonary
      Tuberculosis.

PMID- 29015828
TI  - Tolerance to Enterovioform Tablets.

PMID- 29015829
TI  - Some Biochemical Normals in Bengalis.

PMID- 29015830
TI  - A Case of Post-Concussional Headache.

PMID- 29015831
TI  - Solitary Splenic Cyst: Report of a Case.

PMID- 29015832
TI  - Cerebral Embolism Following Antrum Puncture.

PMID- 29015833
TI  - Malarial Infection in the New Born.

PMID- 29015834
TI  - A Case of Retroperitoneal Abscess.

PMID- 29015835
TI  - Tropical Pyomyositis (Bung-Pagga's Disease).

PMID- 29015836
TI  - Abstracts from Reports.

PMID- 29015837
TI  - Two Cases of Anthrax Treated with Sulphanilamide.

PMID- 29015838
TI  - A Simplified Leucotome.

PMID- 29015839
TI  - A Note on Two Cases of 'Sliding' Hernia.

PMID- 29015840
TI  - Cerebral Malaria.

PMID- 29015841
TI  - The Parasitology of Malaria among Destitutes in Calcutta during and after the
      Bengal Famine of 1943.

PMID- 29015842
TI  - A New Manifestation of Ariboflavinosis. Lesions of the Vulva.

PMID- 29015843
TI  - Sulphonamide Amblyopia and Its Treatment with Nicotinic Acid.

PMID- 29015845
TI  - Quinine Sulphate for Intramuscular Injections.

PMID- 29015844
TI  - 'Tropical Ulcer' in East Khandesh. Treatment with Sulphathiazole Cod-Liver Oil
      Paste.

PMID- 29015846
TI  - Treatment of Cholera with Atebrin.

PMID- 29015847
TI  - Penicillin in the Treatment of Wounds.

PMID- 29015848
TI  - Synthesis of Vitamins in the Human Gut.

PMID- 29015850
TI  - Service Notes.

PMID- 29015849
TI  - A Case of Tropical Eosinophilia Developing Agranulocytic Angina during Arsenical
      Therapy.

PMID- 29015851
TI  - Typhus in Kashmir.

PMID- 29015852
TI  - Pulmonary Arteriosclerosis Producing Unusual Murmurs at the Base of the Heart.

PMID- 29015853
TI  - Post-Sulphapyridine Anuria.

PMID- 29015854
TI  - Investigation into the Toxicity of Large Volume Serum Transfusions.

PMID- 29015855
TI  - Medical News.

PMID- 29015856
TI  - Intradiploic Epidermoid of the Skull.

PMID- 29015857
TI  - Gnathostome Infection of the Eye.

PMID- 29015858
TI  - Current Topics.

PMID- 29015859
TI  - Malarial Nephritis.

PMID- 29015860
TI  - Massive Epistaxis in Benign Tertian Malaria.

PMID- 29015862
TI  - Sulphonamides in Urine: A Simple Test for Detection.

PMID- 29015861
TI  - Control of Sepsis in War Wounds by Pre-Surgical Treatment: Preliminary Report.

PMID- 29015863
TI  - Current Topics.

PMID- 29015864
TI  - Maternal Blood in Whooping Cough.

PMID- 29015865
TI  - Typhus Fever in Gilgit.

PMID- 29015866
TI  - The Causation of Cancer with Special Reference to Endocrine Influence.

PMID- 29015867
TI  - A Case of Gas Gangrene and Tetanus Treated with Sulphapyridine.

PMID- 29015868
TI  - Tuberculosis of the Skull.

PMID- 29015869
TI  - Complement Fixation Test for Kala-Azar.

PMID- 29015871
TI  - Exo-Erythrocytic Forms of Malaria Parasites.

PMID- 29015870
TI  - Fracture-Dislocation of the Cervical Spine. A Case Report.

PMID- 29015872
TI  - Famine OEdema and Its Treatment with Mercurial Diuretics.

PMID- 29015873
TI  - Surgical Emphysema as a Diagnostic Sign of Gastric or Intestinal Perforation.

PMID- 29015874
TI  - Sulphonamides in Peritoneal Surgery.

PMID- 29015876
TI  - Abstracts from Reports.

PMID- 29015875
TI  - Two Cases Showing Cerebral Symptoms after Treatment with Quinacrine for Malaria.

PMID- 29015877
TI  - A Case of Viper Bite.

PMID- 29015878
TI  - Inguinal Hernias: Their Commoner Varieties and Operative Treatment.

PMID- 29015879
TI  - An Experiment in Rural Medical Relief.

PMID- 29015880
TI  - Rural Dispensaries in Bengal : Causes of Their Unpopularity and a Plea for Their
      Improvement in the Scheme of Post-War Reorganization of Medical Relief.

PMID- 29015881
TI  - Synergistic Effect of Sulphanilyl Benzamide on V. Cholerae Bacteriophage.

PMID- 29015882
TI  - Report on an Epidemic of Scrub Typhus (K Form) Treated at a General Hospital in
      Burma.

PMID- 29015883
TI  - Ectopia Vesicae: Four Cases: Pyelographic Studies in a Child Aged One Year.

PMID- 29015884
TI  - Dehydration Treated by Continuous Gastric Drip.

PMID- 29015885
TI  - Compound Fracture of the Leg with Gas Gangrene Treated with Penicillin.

PMID- 29015886
TI  - Modified Kligler's Iron Agar Medium for the Isolation of Intestinal Pathogens.

PMID- 29015887
TI  - Prostigmine in a Case of Paroxysmal Tachycardia.

PMID- 29015888
TI  - A Case of Complete Inversion of Uterus.

PMID- 29015889
TI  - Empyema with Contra-Lateral Pneumonia Treated with Penicillin.

PMID- 29015891
TI  - Medical News.

PMID- 29015890
TI  - Ocular Complications in Smallpox.

PMID- 29015892
TI  - A Case of Hyperglycaemia Showing an Unusual Response to Thyroid Therapy.

PMID- 29015894
TI  - Service Notes.

PMID- 29015893
TI  - Sketch of a Mosquito-Proof Room.

PMID- 29015895
TI  - The Use of Blood Tests in Excluding Paternity and Maternity.

PMID- 29015897
TI  - Streptococcal Meningitis in an Infant Treated with Penicillin.

PMID- 29015896
TI  - A Case of Acute Yellow Atrophy of the Liver.

PMID- 29015898
TI  - Sulphathiazole and Acute Mastoiditis.

PMID- 29015900
TI  - Congenital Absence of the Shaft of the Femur on Both Sides.

PMID- 29015899
TI  - Heparin in Penicillin Therapy.

PMID- 29015902
TI  - Service Notes.

PMID- 29015901
TI  - Caesarean Section.

PMID- 29015903
TI  - Tropical Eosinophilia.

PMID- 29015904
TI  - Current Topics.

PMID- 29015905
TI  - The Immediate Need of Reform of the Medical Councils of India.

PMID- 29015906
TI  - Abstracts from Reports.

PMID- 29015907
TI  - Treatment of Indian Kala-Azar.

PMID- 29015908
TI  - General Medical Practice.

PMID- 29015909
TI  - Medical News.

PMID- 29015910
TI  - Limitations of Sulphonamide Therapy in Surgery.

PMID- 29015911
TI  - Current Topics.

PMID- 29015912
TI  - Three Statements on the Health of India and Associated Observations.

PMID- 29015913
TI  - Service Notes.

PMID- 29015915
TI  - Pharmacy Bill.

PMID- 29015914
TI  - Medical News.

PMID- 29015916
TI  - Service Notes.

PMID- 29015917
TI  - Abstracts from Reports.

PMID- 29015918
TI  - Medical News.

PMID- 29015919
TI  - Paludrine (M.4888).

PMID- 29015921
TI  - Current Topics.

PMID- 29015920
TI  - Parenteric Fever.

PMID- 29015922
TI  - Penicillin Therapy.

PMID- 29015924
TI  - Intravenous Anaesthesia.

PMID- 29015923
TI  - Infective Hepatitis and Catarrhal Jaundice.

PMID- 29015925
TI  - Service Notes.

PMID- 29015926
TI  - Medical News.

PMID- 29015928
TI  - Service Notes.

PMID- 29015927
TI  - Current Topics.

PMID- 29015929
TI  - Abstracts from Reports.

PMID- 29015930
TI  - Medical News.

PMID- 29015931
TI  - Power and Procedure of the General Medical Council of Great Britain and Ireland,
      and Their Influence on Indian Medical Affairs.

PMID- 29015933
TI  - Current Topics.

PMID- 29015932
TI  - Venereal Diseases Number.

PMID- 29015934
TI  - Any Questions.

PMID- 29015936
TI  - Service Notes.

PMID- 29015935
TI  - Pharmacy Bill.

PMID- 29015938
TI  - Current Topics.

PMID- 29015937
TI  - Stethoscope versus X-Rays.

PMID- 29015939
TI  - Abstracts from Reports.

PMID- 29015940
TI  - Medical News.

PMID- 29015942
TI  - Vitaminized Chocolates.

PMID- 29015941
TI  - Erratum: The Wassermann Positive Rate of Cases from Hospitals and Venereal
      Clinics of Calcutta in 1939, 1943, 1944 and 1945.
AB  - [This corrects the article on p. 633 in vol. 80.].

PMID- 29015944
TI  - Service Notes.

PMID- 29015943
TI  - Fireside Fantasies.

PMID- 29015945
TI  - Any Questions.

PMID- 29015946
TI  - Vaccination for Smallpox.

PMID- 29015947
TI  - Storage of Penicillin.

PMID- 29015948
TI  - Antibiotics.

PMID- 29015949
TI  - Correspondence.

PMID- 29015951
TI  - Medical News.

PMID- 29015950
TI  - Current Topics.

PMID- 29015952
TI  - Current Topics.

PMID- 29015953
TI  - Service Notes.

PMID- 29015955
TI  - Abstracts from Reports.

PMID- 29015954
TI  - Sulphapyridine and Sulphathiazole as Helminthagogue.

PMID- 29015956
TI  - Hair on the Index Finger.

PMID- 29015957
TI  - Any Questions.

PMID- 29015958
TI  - Erratum: Serological Technique.
AB  - [This corrects the article on p. 352 in vol. 81.].

PMID- 29015959
TI  - Synthetic Folic Acid.

PMID- 29015960
TI  - Medical News.

PMID- 29015961
TI  - Any Questions.

PMID- 29015962
TI  - Current Topics.

PMID- 29015963
TI  - Service Notes.

PMID- 29015964
TI  - Erratum: Penicillin Therapy Compared with Sulphonamide Therapy in Cerebrospinal
      Fever.
AB  - [This corrects the article on p. 113 in vol. 81.].

PMID- 29015965
TI  - Vaccination for Smallpox.

PMID- 29015967
TI  - Medical News.

PMID- 29015968
TI  - Erratum: Treatment of Oriental Sore by X-Rays.
AB  - [This corrects the article on p. 251 in vol. 81.].

PMID- 29015969
TI  - Venereal Diseases Other Than Syphilis, Gonorrhoea and Soft Sore.

PMID- 29015970
TI  - Abstracts from Reports.

PMID- 29015972
TI  - Venereal Diseases in India.

PMID- 29015971
TI  - Service Notes.

PMID- 29015973
TI  - Abstracts from Reports.

PMID- 29015974
TI  - Current Topics.

PMID- 29015976
TI  - Medical News.

PMID- 29015975
TI  - AEtiology of Nephritis.

PMID- 29015978
TI  - Comfort for the Middle-Aged.

PMID- 29015977
TI  - Pharmacy Bill.

PMID- 29015979
TI  - Pharmacy Bill.

PMID- 29015981
TI  - Feeding the Worker.

PMID- 29015980
TI  - Transmission of Kala-Azar.

PMID- 29015983
TI  - Abstracts from Reports.

PMID- 29015982
TI  - Service Notes.

PMID- 29015985
TI  - Drunkenness: Results of Chemical Tests of Blood Taken from Unconscious Person-Use
      during Trial-Self-Incrimination.

PMID- 29015984
TI  - Pharmacy Bill.

PMID- 29015986
TI  - Medical News.

PMID- 29015987
TI  - Erratum: Ocular Manifestations of Avitaminosis in Adults.
AB  - [This corrects the article on p. 188 in vol. 81.].

PMID- 29015988
TI  - Evidence Held Sufficient to Show That Death Caused by Tetanus Arose out of the
      Deceased's Employment.

PMID- 29015989
TI  - Current Topics.

PMID- 29015990
TI  - Medical News.

PMID- 29015991
TI  - Recent Developments in Tuberculosis Control in the West and Their Application to
      India.

PMID- 29015992
TI  - Metallic Dermatitis.

PMID- 29015994
TI  - Medical News.

PMID- 29015993
TI  - Transmission of Wuchereria Bancrofti.

PMID- 29015996
TI  - Tuberculosis in Sailors in Calcutta and Associated Considerations.

PMID- 29015995
TI  - Encephalitis in Jamshedpur.

PMID- 29015997
TI  - A Report on Cases of Enteric Fever Treated with Combined Chloramphenicol and
      Aureomycin.

PMID- 29015998
TI  - Incidence of Lung Diseases among Seamen Examined at the Port of Calcutta in 1952.

PMID- 29015999
TI  - Fifty Years Ago.

PMID- 29016000
TI  - Current Topics, Etc.

PMID- 29016001
TI  - Testing of Insoluble Drugs and Oils for Their Bactericidal Properties.

PMID- 29016002
TI  - Twenty Five Years Ago.

PMID- 29016003
TI  - Typhoid Fever.

PMID- 29016004
TI  - Lipid Phosphorus in Plasma.

PMID- 29016005
TI  - Seventy Five Years Ago.

PMID- 29016007
TI  - Compounds and Complexes.

PMID- 29016006
TI  - Hypertension: A New ("Informative") Method for Its Evaluation, Study and Follow
      Up.

PMID- 29016008
TI  - Fifty Years Ago.

PMID- 29016009
TI  - Erratum: Laboratory Diagnosis of Smallpox.
AB  - [This corrects the article on p. 468 in vol. 89.].

PMID- 29016010
TI  - Plasmacytoma.

PMID- 29016011
TI  - Master Mind in Medicine William Osler.

PMID- 29016012
TI  - Incidence and Distribution of Corneal Ulcer.

PMID- 29016013
TI  - Twenty Five Years Ago.

PMID- 29016014
TI  - Current Topics, Etc.

PMID- 29016015
TI  - Terramycin in Chronic Amoebic Dysentry.

PMID- 29016016
TI  - Clinical Observations with New Amoebicidal Drugs.

PMID- 29016018
TI  - Medical News.

PMID- 29016017
TI  - Two Problem Chest Cases.

PMID- 29016020
TI  - Pharmacopaeias and Adjuvants.

PMID- 29016019
TI  - Seventy Five Years Ago.

PMID- 29016021
TI  - Comparison of Nutrient Values of Individual Diets Found by Calculation from Food
      Tables and by Chemical Analysis.

PMID- 29016023
TI  - Fifty Years Ago.

PMID- 29016022
TI  - A Study on the Anthelmintic Action of the Cashew-Nut Shell Oil.

PMID- 29016024
TI  - Disseminated Hypersensitisation Neuropathy.

PMID- 29016025
TI  - Medical News.

PMID- 29016026
TI  - Early Widal and Chloromycetin in Typhoid Fever.

PMID- 29016027
TI  - Current Topics, Etc.

PMID- 29016028
TI  - Transvestism in the Male and beyond.

PMID- 29016029
TI  - Laboratory Diasnosis of Small Pox.

PMID- 29016030
TI  - Mercurial Diuretic in Thelapy with Special Reffrence to Control of Ascites in
      Hepatic Cirrhosis and Its Toxic Manifestation with Case Reports.

PMID- 29016031
TI  - Neurolosical Manifestations of Diabetes Mellitus.

PMID- 29016032
TI  - Errata.
AB  - [This corrects the article on p. 742 in vol. 89.].

PMID- 29016033
TI  - Errata.
AB  - [This corrects the article on p. 736 in vol. 89.].

PMID- 29016035
TI  - Errata.
AB  - [This corrects the article on p. 717 in vol. 89.].

PMID- 29016034
TI  - Fireside Fantasies.

PMID- 29016037
TI  - Errata.
AB  - [This corrects the article on p. 485 in vol. 89.].

PMID- 29016036
TI  - Erratum: Old Tales Retold with Fresh Comments.
AB  - [This corrects the article on p. 552 in vol. 89.].

PMID- 29016038
TI  - Pantry, Kitchen & Servant's Quarters.

PMID- 29016039
TI  - Twenty Five Years Ago.

PMID- 29016040
TI  - How the Students of Olso Entered the Hotel Business.

PMID- 29016041
TI  - Errata.
AB  - [This corrects the article on p. 166 in vol. 89.].

PMID- 29016042
TI  - Errata.
AB  - [This corrects the article on p. 481 in vol. 89.].

PMID- 29016043
TI  - Errata.
AB  - [This corrects the article on p. 523 in vol. 89.].

PMID- 29016044
TI  - Errata.
AB  - [This corrects the article on p. 664 in vol. 89.].

PMID- 29016045
TI  - Errata.
AB  - [This corrects the article on p. 523 in vol. 89.].

PMID- 29016047
TI  - Fifty Years Ago.

PMID- 29016046
TI  - Studies of Adreno-Cortical Function Tests in Portal Cirrhosis.

PMID- 29016048
TI  - Colds, Cougas and Fevers of Winter in Calcutta.

PMID- 29016049
TI  - Errata.
AB  - [This corrects the article on p. 541 in vol. 89.].

PMID- 29016051
TI  - Errata.
AB  - [This corrects the article on p. 395 in vol. 89.].

PMID- 29016050
TI  - A Priliminary Note on the Pharmacological Study on Reserpine a New Alkaloid
      Isolated from Rauwolfia Serpentina.

PMID- 29016052
TI  - Current Topics, Etc.

PMID- 29016053
TI  - Errata.
AB  - [This corrects the article on p. 290 in vol. 89.].

PMID- 29016054
TI  - Genesis of Nutritional Oedema.

PMID- 29016056
TI  - Seventy Five Years Ago.

PMID- 29016055
TI  - A System of Automassage.

PMID- 29016057
TI  - Medical News.

PMID- 29016058
TI  - Fifty Years Ago.

PMID- 29016059
TI  - An Epidemic of Kock Weeks Conjunctivities.

PMID- 29016061
TI  - Seventy Five Years Ago.

PMID- 29016060
TI  - Trichinella Spiralis Infection in a Cat That Died in the Zoological Gardens,
      Bombay.

PMID- 29016062
TI  - Twenty Five Years Ago.

PMID- 29016063
TI  - Defence Industries in India.

PMID- 29016064
TI  - Social Welfare.

PMID- 29016065
TI  - Microfilarial Periodicity.

PMID- 29016066
TI  - Treatment of Amoebiasis.

PMID- 29016067
TI  - Isonicotinic Acid Hydrazide in the Treatment of Lupus Vulgaris.

PMID- 29016068
TI  - The Presidency General Hospital Calcutta.

PMID- 29016069
TI  - Etiology of Acute Retention of Urine in Elderly Individuals Based on Cases.

PMID- 29016070
TI  - Role of Non-Political Agencies in Easing World Tensions Stressed by Prime
      Minister Nehru before WHO Regional Committee.

PMID- 29016071
TI  - Some Aspects of Family Planning Rajkumari Amrit Kaur's Broadcast.

PMID- 29016072
TI  - Work for Welfare of the Blind.

PMID- 29016073
TI  - Medical News.

PMID- 29016074
TI  - Current Topics.

PMID- 29016075
TI  - Notes on Some Remedies. XIX. Drugs in Anaemias. Part III.

PMID- 29016076
TI  - Active monitoring vs treatment for localised prostate cancer.

PMID- 29016077
TI  - Just Do It.

PMID- 29016079
TI  - Looking the Other Way.

PMID- 29016083
TI  - Microbes Evolved to Colonize Different Parts of Human Body

PMID- 29016084
TI  - Research Shows Trends for Dental Care in ED

PMID- 29016085
TI  - Prompt diagnosis of AF lowers risk of complications.
AB  - Atrial fibrillation (AF) is the most common sustained heart rhythm disturbance.
      Estimates suggest an AF prevalence as high as 2% in adults with an exponential
      relationship with increasing age. AF is associated with a 1.5-2 fold increased
      risk of death, and is responsible for 20-30% of all strokes. There are strong
      relationships with hypertension, heart failure, coronary artery disease (CAD),
      valvular heart disease, obesity, diabetes mellitus, COPD, obstructive sleep
      apnoea, chronic kidney disease and lifestyle factors such as increased alcohol
      intake, strenuous physical exercise and smoking. Assessment should include
      physical examination (blood pressure measurement, cardiovascular examination to
      look for valvular heart disease or heart failure and lung examination looking for
      signs of lung disease or pulmonary oedema), blood tests, including urea and
      electrolytes, liver function tests, full blood count, blood glucose and thyroid
      function tests. Signs of haemodynamic instability or severe symptoms (unstable
      angina, evolving TIA or stroke, heart failure or severe bradycardia) should be
      promptly identified and lead to urgent referral to specialist care. The CHA2DS2
      VASc risk stratification score is recommended to assess stroke risk in patients
      with AF. Oral anticoagulation should be offered to those with a CHA2DS2-VASc
      score >= 2, and considered for men with a score of 1 and women with a score of 2.
      Risk of severe bleeding with warfarin should also be assessed using the HAS-BLED
      score.

PMID- 29016087
TI  - Link Confirmed Between Drug Use and Poor Dental Health

PMID- 29016086
TI  - Oral Health Key to Understanding Humanity's Past

PMID- 29016089
TI  - Mouse Teeth Provide Insights Into Tissue Regeneration

PMID- 29016088
TI  - Early recognition vital in acute coronary syndrome.
AB  - Acute coronary syndrome (ACS) includes both ST (STEMI) and non ST elevation
      (NSTEMI) MI, and unstable angina. The common pathological process underlying MI
      involves thrombus formation on top of a complex atheromatous plaque, resulting in
      partial or complete occlusion of the coronary artery and myocyte necrosis.
      Unstable angina is defined as ischaemia at rest or on minimal exertion in the
      absence of myocyte necrosis. Patients with ACS typically present with chest pain;
      classically central chest pain that radiates to the left arm. Additional symptoms
      include dyspnoea, nausea, sweating and syncope. Patients can present atypically
      with gastric symptoms. These are often more common in patients with diabetes,
      women and the elderly. Clinical risk factors should also be considered when
      diagnosing ACS as this increases the likelihood of a positive diagnosis. Risk
      factors include: being older, male, a current or former smoker, known coronary
      artery disease (CAD), peripheral vascular disease, diabetes,
      hypercholesterolaemia, renal failure and a family history of CAD.A 12-lead ECG
      should be performed if possible within 10 minutes of presentation or ideally at
      first contact with the emergency services. Troponin should be measured on
      admission and at 12 hours. Ideally high sensitivity troponin should be measured
      as this has higher negative predictive values for MI and enables earlier
      detection of acute MI. A chest x-ray should also be carried out to assess for
      thoracic pathologies. An echocardiogram should be performed during admission in
      all patients with NSTEMI and STEMI.

PMID- 29016091
TI  - Peptide Histatin 1 May Help Implants Integrate

PMID- 29016090
TI  - Managing actinic keratosis in primary care.
AB  - Actinic, or solar, keratosis is caused by chronic ultraviolet-induced damage to
      the epidermis. In the UK, 15-23% of individuals have actinic keratosis lesions.
      Risk factors include: advanced age; male gender; cumulative sun exposure or
      phototherapy; Fitzpatrick skin phototypes I-II; long-term immuno-suppression and
      genetic syndromes e.g. xeroderma pigmentosum and albinism. Actinic keratoses are
      regarded by some authorities as premalignant lesions that may transform into
      invasive squamous cell carcinoma (SCC) and by others as in situ SCC that may
      progress to an invasive stage. The risk of malignant change appears low; up to
      0.5% per lesion per year. Up to 20-30% of lesions may spontaneously regress but
      in the absence of any reliable prognostic clinical indicators regarding malignant
      potential active treatment is considered appropriate. Actinic keratosis lesions
      may present as discrete hyperkeratotic papules, cutaneous horns, or more subtle
      flat lesions on sun-exposed areas of skin. The single most helpful diagnostic
      sign is an irregularly roughened surface texture: a sandpaper-like feel almost
      always indicates actinic damage. Dermatoscopy can be helpful in excluding signs
      of basal cell carcinoma when actinic keratosis is non-keratotic. It is always
      important to consider the possibility of SCC. The principal indication for
      referral to secondary care is the possibility of cutaneous malignancy. However,
      widespread and severe actinic damage in patients who are immunosuppressed is also
      a reason for referral.

PMID- 29016092
TI  - Sports Dentistry-More Than Mouthguards.

PMID- 29016093
TI  - Current Concepts in Concussion: A Review.

PMID- 29016101
TI  - Molecular Orbital Principles of Oxygen-Redox Battery Electrodes.
AB  - Lithium-ion batteries are key energy-storage devices for a sustainable society.
      The most widely used positive electrode materials are LiMO2 (M: transition
      metal), in which a redox reaction of M occurs in association with Li+
      (de)intercalation. Recent developments of Li-excess transition-metal oxides,
      which deliver a large capacity of more than 200 mAh/g using an extra redox
      reaction of oxygen, introduce new possibilities for designing higher energy
      density lithium-ion batteries. For better engineering using this fascinating new
      chemistry, it is necessary to achieve a full understanding of the reaction
      mechanism by gaining knowledge on the chemical state of oxygen. In this review, a
      summary of the recent advances in oxygen-redox battery electrodes is provided,
      followed by a systematic demonstration of the overall electronic structures based
      on molecular orbitals with a focus on the local coordination environment around
      oxygen. We show that a pi-type molecular orbital plays an important role in
      stabilizing the oxidized oxygen that emerges upon the charging process. Molecular
      orbital principles are convenient for an atomic-level understanding of how
      reversible oxygen-redox reactions occur in bulk, providing a solid foundation
      toward improved oxygen-redox positive electrode materials for high energy-density
      batteries.

PMID- 29016100
TI  - Rapid Diffusion and Nanosegregation of Hydrogen in Magnesium Alloys from Exposure
      to Water.
AB  - Hydrogen gas is formed when Mg corrodes in water; however, the manner and extent
      to which the hydrogen may also enter the Mg metal is poorly understood. Such
      knowledge is critical as stress corrosion cracking (SCC)/embrittlement phenomena
      limit many otherwise promising structural and functional uses of Mg. Here, we
      report via D2O/D isotopic tracer and H2O exposures with characterization by
      secondary ion mass spectrometry, inelastic neutron scattering vibrational
      spectrometry, electron microscopy, and atom probe tomography techniques direct
      evidence that hydrogen rapidly penetrated tens of micrometers into Mg metal after
      only 4 h of exposure to water at room temperature. Further, technologically
      important microalloying additions of <1 wt % Zr and Nd used to improve the
      manufacturability and mechanical properties of Mg significantly increased the
      extent of hydrogen ingress, whereas Al additions in the 2-3 wt % range did not.
      Segregation of hydrogen species was observed at regions of high Mg/Zr/Nd
      nanoprecipitate density and at Mg(Zr) metastable solid solution microstructural
      features. We also report evidence that this ingressed hydrogen was unexpectedly
      present in the alloy as nanoconfined, molecular H2. These new insights provide a
      basis for strategies to design Mg alloys to resist SCC in aqueous environments as
      well as potentially impact functional uses such as hydrogen storage where
      increased hydrogen uptake is desired.

PMID- 29016102
TI  - Chip-Based Multicapillary Column with Maximal Interconnectivity to Combine
      Maximum Efficiency and Maximum Loadability.
AB  - On the basis of our previous work on the design of pillar array columns for
      liquid chromatography, we report on a new pillar array design for high
      efficiency, high volumetric loadability gas chromatography columns. The proposed
      pillar array configuration leads to a column design which can either be
      considered as a packed bed with perfectly ordered and uniform flow paths or as
      multicapillary columns (8 parallel tracks) with a maximal interconnectivity
      between the flow paths to avoid the so-called polydispersity effect (dispersion
      arising from the inevitable differences in migration velocity between parallel
      flow paths). Despite our relative inexperience with column coating, and most
      probably (not supported by data) suffering from the same problem of stationary
      phase pooling in the right-angled corners of the flow-through channels as other
      chip-based GC devices, the efficiencies obtained in a L = 70 cm long and 75 MUm
      deep and 6.195 mm wide chip for, respectively, quasi-unretained and retained
      components (k = 7) went up to N = 60 000 and 12 500 under isothermal conditions
      using H2 as carrier gas and a downstream restriction. Under programmed
      temperature conditions (Ti = 80  degrees C, Tf = 175  degrees C at 30  degrees
      C/min, and a H2 flow of 0.4 mL/min), a peak capacity of 170 was obtained in 3.6
      min. For retained compounds, the optimal flow rate is found to be on the order of
      0.4 mL/min, achieved at an operating pressure of 2.3 bar. Intrinsically, the
      column combines the efficiency of a 75 MUm capillary with the volumetric
      loadability of a 240 MUm capillary.

PMID- 29016104
TI  - diDO-IPTL: A Peptide-Labeling Strategy for Precision Quantitative Proteomics.
AB  - We present an analytical strategy, dimethylation-deuteration and oxygen-exchange
      IPTL (diDO-IPTL), for high-precision, broad-coverage quantitative proteomics. The
      diDO-IPTL approach combines two advances in isobaric peptide terminal labeling
      (IPTL) methodology: first, a one-pot chemical labeling strategy for attaching
      isotopic tags to both the N- and C-termini of tryptic peptides, and second, a
      search engine (based on the Morpheus algorithm) optimized for identification and
      quantification of twinned peaks from peptide fragment ions in MS2 spectra. The
      diDO-IPTL labeling chemistry uses only high-purity, relatively inexpensive
      isotopic reagents (18O water and deuterated formaldehyde) and requires no
      postlabeling cleanup or isotopic impurity corrections. This strategy produces
      proteome-scale relative quantification results with high accuracy and precision,
      suitable for the detection of small protein abundance variations between complex
      biological samples. In a two-proteome mixture experiment, diDO-IPTL
      quantification discriminates 1.5-fold changes in abundance of over 1000 proteins
      with 88% accuracy. The diDO-IPTL methodology is a high-precision, economical
      approach to quantitative proteomics that is applicable to a wide variety of
      sample types.

PMID- 29016103
TI  - Comparison of Enrichment Methods for Intact N- and O-Linked Glycopeptides Using
      Strong Anion Exchange and Hydrophilic Interaction Liquid Chromatography.
AB  - Heterogeneity of protein glycosylation poses great challenges for analysis that
      is key to understand structure and function of glycoproteins. Resolving this
      conundrum requires efficient and specific enrichment of intact glycopeptides for
      identification and quantitation. To this end, hydrophilic interaction
      chromatography (HILIC) has been commonly used to enrich intact N- and O-linked
      glycopeptides. However, its effectiveness to enrich isobarically labeled
      glycopeptides remains unclear. Here, we studied three different enrichment
      methods for enrichment of N- and O-linked glycopeptides. It was found that
      removal of N-glycans prior to enrichment of O-linked glycopeptides by HILIC
      improved identification of O-linked glycopeptides by mass spectrometry. We also
      compared the enrichment of intact N- and O-linked glycopeptides using other
      chromatography methods and found that using cartridges containing materials for
      strong anion exchange (SAX) chromatography increased yield and identification of
      N- and O-linked glycopeptides. The enrichment of O-linked glycopeptides was
      further improved when a Retain AX cartridge (RAX) was used. In particular,
      isobaric tag labeled glycopeptides after C18 desalting could be readily enriched
      by SAX and RAX cartridges but not by HILIC to enable quantitative
      glycoproteomics. It is anticipated that the use of SAX and RAX cartridges will
      facilitate broad applications of identifications and quantitation of
      glycoproteins.

PMID- 29016105
TI  - Aggregation-Induced Emission Luminogen with Deep-Red Emission for Through-Skull
      Three-Photon Fluorescence Imaging of Mouse.
AB  - Imaging the brain with high integrity is of great importance to neuroscience and
      related applications. X-ray computed tomography (CT) and magnetic resonance
      imaging (MRI) are two clinically used modalities for deep-penetration brain
      imaging. However, their spatial resolution is quite limited. Two-photon
      fluorescence microscopic (2PFM) imaging with its femtosecond (fs) excitation
      wavelength in the traditional near-infrared (NIR) region (700-1000 nm) is able to
      realize deep-tissue and high-resolution brain imaging. However, it requires
      craniotomy and cranial window or skull-thinning techniques due to photon
      scattering of the excitation light. Herein, based on a type of aggregation
      induced emission luminogen (AIEgen) DCDPP-2TPA with a large three-photon
      absorption (3PA) cross section at 1550 nm and deep-red emission, we realized
      through-skull three-photon fluorescence microscopic (3PFM) imaging of mouse
      cerebral vasculature without craniotomy and skull-thinning. Reduced photon
      scattering of a 1550 nm fs excitation laser allowed it to effectively penetrate
      the skull and tightly focus onto DCDPP-2TPA nanoparticles (NPs) in the cerebral
      vasculature, generating bright three-photon fluorescence (3PF) signals. In vivo
      3PF images of the cerebral vasculature at various vertical depths were obtained,
      and a vivid 3D reconstruction of the vascular architecture beneath the skull was
      built. As deep as 300 MUm beneath the skull, small blood vessels of 2.4 MUm could
      still be recognized.

PMID- 29016106
TI  - Characterizations of the Interactions between Escherichia coli Periplasmic
      Chaperone HdeA and Its Native Substrates during Acid Stress.
AB  - The bacterial acid-resistant chaperone HdeA is a "conditionally disordered"
      protein that functions at low pH when it undergoes a transition from a well
      folded dimer to an unfolded monomer. The dimer dissociation and unfolding
      processes result in exposure of hydrophobic surfaces that allows binding to a
      broad range of client proteins. To fully elucidate the chaperone mechanism of
      HdeA, it is crucial to understand how the activated HdeA interacts with its
      native substrates during acid stress. Herein, we present a nuclear magnetic
      resonance study of the pH-dependent HdeA-substrate interactions. Our results show
      that the activation of HdeA is not only induced by acidification but also
      regulated by the presence of unfolded substrates. The variable extent of
      unfolding of substrates differentially regulates the HdeA-substrate interaction,
      and the binding further affects the HdeA conformation. Finally, we show that HdeA
      binds its substrates heterogeneously, and the "amphiphilic" model for HdeA
      substrate interaction is discussed.

PMID- 29016108
TI  - Vanadium Redox Flow Batteries Using meta-Polybenzimidazole-Based Membranes of
      Different Thicknesses.
AB  - 15, 25, and 35 MUm thick meta-polybenzimidazole (PBI) membranes are doped with
      H2SO4 and tested in a vanadium redox flow battery (VRFB). Their performances are
      compared with those of Nafion membranes. Immersed in 2 M H2SO4, PBI absorbs about
      2 mol of H2SO4 per mole of repeat unit. This results in low conductivity and low
      voltage efficiency (VE). In ex-situ tests, meta-PBI shows a negligible crossover
      of V3+ and V4+ ions, much lower than that of Nafion. This is due to electrostatic
      repulsive forces between vanadium cations and positively charged protonated PBI
      backbones, and the molecular sieving effect of PBI's nanosized pores. It turns
      out that charge efficiency (CE) of VRFBs using meta-PBI-based membranes is
      unaffected by or slightly increases with decreasing membrane thickness. Thick
      meta-PBI membranes require about 100 mV larger potentials to achieve the same
      charging current as thin meta-PBI membranes. This additional potential may
      increase side reactions or enable more vanadium ions to overcome the
      electrostatic energy barrier and to enter the membrane. On this basis, H2SO4
      doped meta-PBI membranes should be thin to achieve high VE and CE. The energy
      efficiency of 15 MUm thick PBI reaches 92%, exceeding that of Nafion 212 and 117
      (N212 and N117) at 40 mA cm-2.

PMID- 29016107
TI  - Continuous Elution Proteoform Identification of Myelin Basic Protein by
      Superficially Porous Reversed-Phase Liquid Chromatography and Fourier Transform
      Mass Spectrometry.
AB  - Myelin basic protein (MBP) plays an important structural and functional role in
      the neuronal myelin sheath. Translated MBP exhibits extreme microheterogeneity
      with numerous alternative splice variants (ASVs) and post-translational
      modifications (PTMs) reportedly tied to central nervous system maturation, myelin
      stability, and the pathobiology of various de- and dys-myelinating disorders.
      Conventional bioanalytical tools cannot efficiently examine ASV and PTM events
      simultaneously, which limits understanding of the role of MBP microheterogeneity
      in human physiology and disease. To address this need, we report on a top-down
      proteomics pipeline that combines superficially porous reversed-phase liquid
      chromatography (SPLC), Fourier transform mass spectrometry (FTMS), data
      independent acquisition (DIA) with nozzle-skimmer dissociation (NSD), and aligned
      data processing resources to rapidly characterize abundant MBP proteoforms within
      murine tissue. The three-tier proteoform identification and characterization
      workflow resolved four known MBP ASVs and hundreds of differentially modified
      states from a single 90 min SPLC-FTMS run on ~0.5 MUg of material. This included
      323 proteoforms for the 14.1 kDa ASV alone. We also identified two novel ASVs
      from an alternative transcriptional start site (ATSS) of the MBP gene as well as
      a never before characterized S-acylation event linking palmitic acid, oleic acid,
      and stearic acid at C78 of the 17.125 kDa ASV.

PMID- 29016109
TI  - Electron-Deficient Near-Infrared Pt(II) and Pd(II) Benzoporphyrins with Dual
      Phosphorescence and Unusually Efficient Thermally Activated Delayed Fluorescence:
      First Demonstration of Simultaneous Oxygen and Temperature Sensing with a Single
      Emitter.
AB  - We report a family of Pt and Pd benzoporphyrin dyes with versatile photophysical
      properties and easy access from cheap and abundant chemicals. Attaching 4 or 8
      alkylsulfone groups onto a meso-tetraphenyltetrabenzoporphyrin (TPTBP)
      macrocylcle renders the dyes highly soluble in organic solvents, photostable, and
      electron-deficient with the redox potential raised up to 0.65 V versus the parent
      porphyrin. The new dyes intensively absorb in the blue (Soret band, 440-480 nm)
      and in the red (Q-band, 620-650 nm) parts of the electromagnetic spectrum and
      show bright phosphorescence at room-temperature in the NIR with quantum yields up
      to 30% in solution. The small singlet-triplet energy gap yields unusually
      efficient thermally activated delayed fluorescence (TADF) at elevated
      temperatures in solution and in polymeric matrices with quantum yields as high as
      27% at 120  degrees C, which is remarkable for benzoporphyrins. Apart from oxygen
      sensing, these properties enable unprecedented simultaneous, self-referenced
      oxygen and temperature sensing with a single indicator dye: whereas oxygen can be
      determined either via the decay time of phosphorescence or TADF, the temperature
      is accessed via the ratio of the two emissions. Moreover, the dyes are efficient
      sensitizers for triplet-triplet annihilation (TTA)-based upconversion making
      possible longer sensitization wavelength than the conventional benzoporphyrin
      complexes. The Pt-octa-sulfone dye also features interesting semireversible
      transformation in basic media, which generates new NIR absorbing species.

PMID- 29016110
TI  - Bacterial Cellulose Ionogels as Chemosensory Supports.
AB  - To fully leverage the advantages of ionic liquids for many applications, it is
      necessary to immobilize or encapsulate the fluids within an inert, robust, quasi
      solid-state format that does not disrupt their many desirable, inherent features.
      The formation of ionogels represents a promising approach; however, many earlier
      approaches suffer from solvent/matrix incompatibility, optical opacity,
      embrittlement, matrix-limited thermal stability, and/or inadequate ionic liquid
      loading. We offer a solution to these limitations by demonstrating a
      straightforward and effective strategy toward flexible and durable ionogels
      comprising bacterial cellulose supports hosting in excess of 99% ionic liquid by
      total weight. Termed bacterial cellulose ionogels (BCIGs), these gels are
      prepared using a facile solvent-exchange process equally amenable to water
      miscible and water-immiscible ionic liquids. A suite of characterization tools
      were used to study the preliminary (thermo)physical and structural properties of
      BCIGs, including no-deuterium nuclear magnetic resonance, differential scanning
      calorimetry, thermogravimetric analysis, scanning electron microscopy, and X-ray
      diffraction. Our analyses reveal that the weblike structure and high
      crystallinity of the host bacterial cellulose microfibrils are retained within
      the BCIG. Notably, not only can BCIGs be tailored in terms of shape, thickness,
      and choice of ionic liquid, they can also be designed to host virtually any
      desired active, functional species, including fluorescent probes, nanoparticles
      (e.g., quantum dots, carbon nanotubes), and gas-capture reagents. In this paper,
      we also present results for fluorescent designer BCIG chemosensor films
      responsive to ammonia or hydrogen sulfide vapors on the basis of incorporating
      selective fluorogenic probes within the ionogels. Additionally, a thermometric
      BCIG hosting the excimer-forming fluorophore 1,3-bis(1-pyrenyl)propane was
      devised which exhibited a ratiometric (two-color) fluorescence output that
      responded precisely to changes in local temperature. The ionogel approach
      introduced here is simple and has broad generality, offering intriguing potential
      in (bio)analytical sensing, catalysis, membrane separations, electrochemistry,
      energy storage devices, and flexible electronics and displays.

PMID- 29016112
TI  - Liquid Structure with Nano-Heterogeneity Promotes Cationic Transport in
      Concentrated Electrolytes.
AB  - Using molecular dynamics simulations, small-angle neutron scattering, and a
      variety of spectroscopic techniques, we evaluated the ion solvation and transport
      behaviors in aqueous electrolytes containing bis(trifluoromethanesulfonyl)imide.
      We discovered that, at high salt concentrations (from 10 to 21 mol/kg), a
      disproportion of cation solvation occurs, leading to a liquid structure of
      heterogeneous domains with a characteristic length scale of 1 to 2 nm. This
      unusual nano-heterogeneity effectively decouples cations from the Coulombic traps
      of anions and provides a 3D percolating lithium-water network, via which 40% of
      the lithium cations are liberated for fast ion transport even in concentration
      ranges traditionally considered too viscous. Due to such percolation networks,
      superconcentrated aqueous electrolytes are characterized by a high lithium
      transference number (0.73), which is key to supporting an assortment of battery
      chemistries at high rate. The in-depth understanding of this transport mechanism
      establishes guiding principles to the tailored design of future superconcentrated
      electrolyte systems.

PMID- 29016113
TI  - Resolution of the Confusion in the Assignments of Configuration for the
      Ciliatamides, Acylated Dipeptides from Marine Sponges.
AB  - Direct comparison of authentic ciliatamide A with four synthetic isomers (1-4) by
      means of NMR and chiral-phase HPLC revealed that ciliatamide A possesses the 12R
      (d-N-MePhe residue) and 22S (l-Lys residue) configurations, which were not
      identical with either our previous assignment or those proposed by others through
      total synthesis. The absolute configuration of the methionine sulfoxide residue
      in ciliatamide D was also revised to be d.

PMID- 29016111
TI  - Crystallinity of Double-Stranded RNA-Antimicrobial Peptide Complexes Modulates
      Toll-Like Receptor 3-Mediated Inflammation.
AB  - Double-stranded RNA (dsRNA) induces production of pro-inflammatory cytokines in
      normal human epidermal keratinocytes (NHEK) by specific binding to endosomal Toll
      like receptor-3 (TLR3). Recently, it has been shown that hyperactivation of TLR3
      in psoriatic keratinocytes by dsRNA can occur in the presence of human
      antimicrobial peptide (AMP) LL37. Here, we combine synchrotron X-ray scattering,
      microscopy, computer simulations, and measurements of NHEK cytokine production to
      elucidate a previously unanticipated form of specific molecular pattern
      recognition. LL37 and similar alpha-helical AMPs can form pro-inflammatory
      nanocrystalline complexes with dsRNA that are recognized by TLR3 differently than
      dsRNA alone. dsRNA complexes that activate IL-6 production in NHEK and those that
      do not are both able to enter cells and co-localize with TLR3. However, the
      crystallinity of these AMP-dsRNA complexes, specifically the geometric spacing
      between parallel dsRNA and the repeat number of ordered dsRNA, strongly
      influences the level of TLR3 activation. Crystalline complexes that present dsRNA
      at a spacing that matches with the steric size of TLR3 can recruit and engage
      multiple TLR3 receptors, driving receptor clustering and immune amplification,
      whereas crystalline complexes that exhibit poor steric matching do not. Reverse
      transcription quantitative PCR of IL-6 during siRNA knockdown of TLR3 confirms
      that cytokine production is due to TLR3: High levels of IL-6 transcription are
      observed for sterically matched complexes without TLR3 knockdown, whereas such
      activity is abrogated with TLR3 knockdown.

PMID- 29016114
TI  - Bimetallic Trifluoroacetates as Single-Source Precursors for Alkali-Manganese
      Fluoroperovskites.
AB  - Alkali-manganese(II) trifluoroacetates were synthesized, and their potential as
      single-source precursors for the solid-state and solution-phase synthesis of
      AMnF3 fluoroperovskites (A = Na, K, Rb, Cs) was demonstrated. Crystals of
      Na2Mn2(tfa)6(tfaH), K2Mn2(tfa)6(tfaH)2.H2O, Rb2Mn2(tfa)6.H2O, and CsMn(tfa)3 (tfa
      = trifluoroacetato) were grown via solvent evaporation and their crystal
      structures solved using single-crystal X-ray diffraction (XRD). Chemical purity
      was confirmed using thermal analyses (TGA/DTA) and Rietveld analysis of powder
      XRD patterns. Thermal decomposition of Na2Mn2(tfa)6(tfaH),
      K2Mn2(tfa)6(tfaH)2.H2O, Rb2Mn2(tfa)6.H2O, and CsMn(tfa)3 in both the solid state
      and solution phase yielded crystalline, single-phase NaMnF3, KMnF3, RbMnF3, and
      CsMnF3 fluoroperovskites, respectively. Nanocrystals (<100 nm) and
      submicrocrystals (<500 nm) were obtained in a mixture of high-boiling-point
      organic solvents. Crystal structures of bimetallic trifluoroacetates displayed a
      variety of building blocks, coordination environments of the alkali atoms, and
      coordination modes of the trifluoroacetato ligand. Alkali-fluorine interactions
      ranging from chemical bonds to short contacts were observed throughout the
      series. The coordination flexibility of the trifluoroacetato ligand was
      attributed to the ability of the -CF3 groups to interact with alkali atoms over a
      broad range of distances. The synthetic approach described in this investigation
      provides a starting point to expand the library of fluorinated single-source
      precursors suitable for solution-phase routes to mixed-metal fluorides.

PMID- 29016115
TI  - Photoreactions of Phenylborylene with Dinitrogen and Carbon Monoxide.
AB  - Formal removal of two bonding partners from boranes, BR3, yields borylenes, RB,
      which have been inferred as reactive intermediates in a number of reactions.
      Phenylborylene (R = C6H5; 1) is accessible from phenyldiazidoborane by
      photochemical extrusion of dinitrogen under matrix isolation conditions.
      Concomitantly, the nitrene PhNBN is formed via phenyl rearrangement. Here we used
      a combination of UV/vis, IR, and ESR spectroscopy under cryogenic matrix
      isolation conditions to investigate the properties and reactivity of
      phenylborylene. We detected an absorption band of phenylborylene at 375 nm (S0 ->
      S2) and tentatively assigned the S0 -> S1 transition to a very weak band at 518
      nm. We also show for the first time that an electrophilic borylene such as 1 can
      react with N2 reversibly and with CO irreversibly under photochemical conditions.
      The corresponding photoproducts PhBNN and PhBCO have triplet electronic ground
      states. Their small E values are in agreement with the linear arrangements Ph-B-N
      N and Ph-B-C-O obtained by density functional theory computations. The D values
      decrease in the series PhNBN > PhBNN > PhBCO and approach the value for
      phenylcarbene (PhCH). Indeed, the boron center in PhBCO is isoelectronic with the
      carbene center in PhCH. The compounds are the first examples of boron analogues
      of diazoalkanes (R2CNN) and ketenes (R2CCO), and their formation may serve as a
      demonstration of the high reactivity of phenylborylene.

PMID- 29016116
TI  - Sugar Cane-Converted Graphene-like Material for the Superhigh Adsorption of
      Organic Pollutants from Water via Coassembly Mechanisms.
AB  - A sugar cane-converted graphene-like material (FZS900) was fabricated by
      carbonization and activation. The material exhibited abundant micropores, water
      stable turbostratic single-layer graphene nanosheets, and a high BET-N2 surface
      area (2280 m2 g-1). The adsorption capacities of FZS900 toward naphthalene,
      phenanthrene, and 1-naphthol were 615.8, 431.2, and 2040 mg g-1, respectively,
      which are much higher than those of previously reported materials. The nonpolar
      aromatic molecules induced the turbostratic graphene nanosheets to agglomerate in
      an orderly manner, forming 2-11 graphene layer nanoloops, while polar aromatic
      compounds induced high dispersion or aggregation of the graphene nanosheets. This
      phase conversion of the nanosized materials after sorption occurred through
      coassembly of the aromatic molecules and the single-layer graphene nanosheets via
      large-area pi-pi interactions. An adsorption-induced partition mechanism was
      further proposed to explain the nanosize effect and nanoscale sorption sites
      observed. This study indicates that commonly available biomass can be converted
      to graphene-like material with superhigh sorption ability in order to remove
      pollutants from the environment via nanosize effects and a coassembly mechanism.

PMID- 29016117
TI  - Formation of Polyphenol-Denatured Protein Flocs in Alcohol Beverages Sweetened
      with Refined Cane Sugars.
AB  - The sporadic appearance of floc from refined, white cane sugars in alcohol
      beverages remains a technical problem for both beverage manufacturers and sugar
      refiners. Cane invert sugars mixed with 60% pure alcohol and water increased
      light scattering by up to ~1000-fold. Insoluble and soluble starch, fat,
      inorganic ash, oligosaccharides, Brix, and pH were not involved in the prevailing
      floc-formation mechanism. Strong polynomial correlations existed between the haze
      floc and indicator values (IVs) (color at 420 nm pH 9.0/color at pH 4.0-an
      indirect measure of polyphenolic and flavonoid colorants) (R2 = 0.815) and
      protein (R2 = 0.819) content of the invert sugars. Ethanol-induced denaturation
      of the protein exposed hydrophobic polyphenol-binding sites that were further
      exposed when heated to 80  degrees C. A tentative mechanism for floc formation
      was advanced by molecular probing with a haze (floc) active protein and
      polyphenol as well as polar, nonpolar, and ionic solvents.

PMID- 29016118
TI  - Plasmolysis-Inspired Nanoengineering of Functional Yolk-Shell Microspheres with
      Magnetic Core and Mesoporous Silica Shell.
AB  - Yolk-shell nanomaterials with a rattle-like structure have been considered ideal
      carriers and nanoreactors. Traditional methods to constructing yolk-shell
      nanostructures mainly rely on multistep sacrificial template strategy. In this
      study, a facile and effective plasmolysis-inspired nanoengineering strategy is
      developed to controllably fabricate yolk-shell magnetic mesoporous silica
      microspheres via the swelling-shrinkage of resorcinol-formaldehyde (RF) upon
      soaking in or removal of n-hexane. Using Fe3O4@RF microspheres as seeds,
      surfactant-silica mesostructured composite is deposited on the swelled seeds
      through the multicomponent interface coassembly, followed by solvent extraction
      to remove surfactant and simultaneously induce shrinkage of RF shell. The
      obtained yolk-shell microspheres (Fe3O4@RF@void@mSiO2) possess a high
      magnetization of 40.3 emu/g, high surface area (439 m2/g), radially aligned
      mesopores (5.4 nm) in the outer shell, tunable middle hollow space (472-638 nm in
      diameter), and a superparamagnetic core. This simple method allows a simultaneous
      encapsulation of Au nanoparticles into the hollow space during synthesis, and it
      leads to spherical Fe3O4@RF@void-Au@mSiO2 magnetic nanocatalysts, which show
      excellent catalysis efficiency for hydrogenation of 4-nitrophenol by NaBH4 with a
      high conversion rate (98%) and magnetic recycling stability.

PMID- 29016119
TI  - 9-Deazapurines as Broad-Spectrum Inhibitors of the ABC Transport Proteins P
      Glycoprotein, Multidrug Resistance-Associated Protein 1, and Breast Cancer
      Resistance Protein.
AB  - P-Glycoprotein (P-gp, ABCB1), multidrug resistance-associated protein 1 (MRP1,
      ABCC1), and breast cancer resistance protein (BCRP, ABCG2) are the three major
      ABC transport proteins conferring resistance to many structurally diverse
      anticancer agents, leading to the phenomenon called multidrug resistance (MDR).
      Much effort has been put into the development of clinically useful compounds to
      reverse MDR. Broad-spectrum inhibitors of ABC transport proteins can be of great
      use in cancers that simultaneously coexpress two or three transporters. In this
      work, we continued our effort to generate new, potent, nontoxic, and multiply
      effective inhibitors of the three major ABC transporters. The best compound was
      active in a very low micromolar concentration range against all three
      transporters and restored sensitivity toward daunorubicin (P-gp and MRP1) and SN
      38 (BCRP) in A2780/ADR (P-gp), H69AR (MRP1), and MDCK II BCRP (BCRP) cells.
      Additionally, the compound is a noncompetitive inhibitor of daunorubicin (MRP1),
      calcein AM (P-gp), and pheophorbide A (BCRP) transport.

PMID- 29016120
TI  - Evaluation of Pyridaben Residues on Fruit Surfaces and Their Stability by a Novel
      On-Line Dual-Frequency Ultrasonic Device and Chemiluminescence Detection.
AB  - In this paper, we first report the development of a highly sensitive and
      economical method for accurate analysis of pyridaben residues on fruits based on
      dual-frequency ultrasonic treatment (DFUT) and flow injection chemiluminescence
      (CL) detection. The DFUT device is made by integrating an ultrasonic bath with an
      ultrasonic probe. Two quartz glass coils (QGC) with different structures have
      been designed and applied to evaluate the function of DFUT in the detection
      process. Recorded data showed that DFUT is an effective method for improving the
      pyridaben CL signal. The signal of pyridaben in response to DFUT is 2.0-3.3 times
      stronger than the response to only the ultrasonic probe at 20 kHz or the
      ultrasonic bath at 40 kHz. In addition, the response obtained from the concentric
      circle QGC is 2.1 times stronger than the response to the spiral tube QGC. Under
      the optimized condition, the proposed method has advantages, such as a wide
      linear range (0.8-100.0 MUg L-1), a high sensitivity (limit of detection of 0.085
      MUg L-1), and good stability (RSDs <= 4.7% in the linear range) for pyridaben
      determination. We apply this method to monitor the residue pyridaben on some
      fruits. The data show that the maximum amounts of the residue on fruit surfaces
      after soaking in water (50 mg L-1, 5 min) are 0.583 mg kg-1 (apple), 0.794 mg kg
      1 (orange), and 0.351 mg kg-1 (pear). However, the concentration of pyridaben in
      the presence of sunlight decreases rapidly, showing its poor light stability.

PMID- 29016122
TI  - Effects of Interaction between Cadmium (Cd) and Selenium (Se) on Grain Yield and
      Cd and Se Accumulation in a Hybrid Rice (Oryza sativa) System.
AB  - A pot experiment was conducted to investigate the interactive effects of cadmium
      (Cd) and selenium (Se) on their accumulation in three rice cultivars, which
      remains unclear. The results showed that Se reduced Cd-induced growth inhibition,
      and increased and decreased Se and Cd concentrations in brown rice, respectively.
      Cadmium concentrations in all tissues of the hybrid were similar to those in its
      male parent yet significantly lower than those in its female parent. Selenium
      reduced Cd accumulation in rice when Cd concentration exceeded 2.0 mg kg-1;
      however Se accumulation depended on the levels of Cd exposure. Finally, Cd had
      minimal effect on Se translocation within the three cultivars. We concluded that
      Cd concentration in brown rice is a heritable trait, making crossbreeding a
      feasible method for cultivating high-yield, low-Cd rice cultivars. Selenium
      effectively decreased the toxicity and accumulation of Cd, and Cd affected Se
      uptake but not translocation.

PMID- 29016121
TI  - Synthesis, Binding Mode, and Antihyperglycemic Activity of Potent and Selective
      (5-Imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine Inhibitors
      of Glycogen Synthase Kinase 3.
AB  - In an effort to identify new antidiabetic agents, we have discovered a novel
      family of (5-imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine
      analogues which are inhibitors of human glycogen synthase kinase 3 (GSK3). We
      developed efficient synthetic routes to explore a wide variety of substitution
      patterns and convergently access a diverse array of analogues. Compound 1 (CHIR
      911, CT-99021, or CHIR-73911) emerged from an exploration of heterocycles at the
      C-5 position, phenyl groups at C-4, and a variety of differently substituted
      linker and aminopyridine moieties attached at the C-2 position. These compounds
      exhibited GSK3 IC50s in the low nanomolar range and excellent selectivity. They
      activate glycogen synthase in insulin receptor-expressing CHO-IR cells and
      primary rat hepatocytes. Evaluation of lead compounds 1 and 2 (CHIR-611 or CT
      98014) in rodent models of type 2 diabetes revealed that single oral doses
      lowered hyperglycemia within 60 min, enhanced insulin-stimulated glucose
      transport, and improved glucose disposal without increasing insulin levels.

PMID- 29016124
TI  - Torsional Barriers to Rotation and Planarization in Heterocyclic Oligomers of
      Value in Organic Electronics.
AB  - In order to understand the conformational behavior of organic components in
      organic electronic devices, we have computed the torsional potentials for a
      library of thiophene-based heterodimers. The accuracy and efficiencies of
      computational methods for these organic materials were benchmarked for 11 common
      density functionals with three Pople basis sets against a Focal Point Analysis
      (FPA) on a model oligothiophene 2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b]
      thiophene (BTTT) system. This study establishes a set of general trends in
      regards to conformational preferences, as well as planarization and rotational
      barriers for a library comprised of common fragments found in organic materials.
      These gas phase structures are compared to experimental crystal structures to
      determine the effect of crystal packing on geometry. Finally, we analyze the
      structure of hole-transporting material DERDTS-TBDT and design a new oligomer
      likely to be planar in the solid state.

PMID- 29016125
TI  - Evaluation of the Factors Impacting the Accuracy of 13C NMR Chemical Shift
      Predictions using Density Functional Theory-The Advantage of Long-Range Corrected
      Functionals.
AB  - The various factors influencing the accuracy of 13C NMR calculations using
      density functional theory (DFT), including the basis set, exchange-correlation
      (XC) functional, and isotropic shielding calculation method, are evaluated. A
      wide selection of XC functionals (over 70) were considered, and it was found that
      long-range corrected functionals offer a significant improvement over the other
      classes of functionals. Based on a thorough study, it is recommended that for
      calculating NMR chemical shifts (delta) one should use the CSGT method, the COSMO
      solvation model, and the LC-TPSSTPSS exchange-correlation functional in
      conjunction with the cc-pVTZ basis set. A selection of problems in natural
      product identification are considered in light of the newly recommended level of
      theory.

PMID- 29016126
TI  - Exact Open Quantum System Dynamics Using the Hierarchy of Pure States (HOPS).
AB  - We show that the general and numerically exact Hierarchy of Pure States method
      (HOPS) is very well applicable to calculate the reduced dynamics of an open
      quantum system. In particular, we focus on environments with a sub-Ohmic spectral
      density (SD) resulting in an algebraic decay of the bath correlation function
      (BCF). The universal applicability of HOPS, reaching from weak to strong coupling
      for zero and nonzero temperature, is demonstrated by solving the spin-boson model
      for which we find perfect agreement with other methods, each one suitable for a
      special regime of parameters. The challenges arising in the strong coupling
      regime are not only reflected in the computational effort needed for the HOPS
      method to converge but also in the necessity for an importance sampling
      mechanism, accounted for by the nonlinear variant of HOPS. In order to include
      nonzero-temperature effects in the strong coupling regime we found that it is
      highly favorable for the HOPS method to use the zero-temperature BCF and include
      temperature via a stochastic Hermitian contribution to the system Hamiltonian.

PMID- 29016123
TI  - ProSelection: A Novel Algorithm to Select Proper Protein Structure Subsets for in
      Silico Target Identification and Drug Discovery Research.
AB  - Molecular docking is widely applied to computer-aided drug design and has become
      relatively mature in the recent decades. Application of docking in modeling
      varies from single lead compound optimization to large-scale virtual screening.
      The performance of molecular docking is highly dependent on the protein
      structures selected. It is especially challenging for large-scale target
      prediction research when multiple structures are available for a single target.
      Therefore, we have established ProSelection, a docking preferred-protein
      selection algorithm, in order to generate the proper structure subset(s). By the
      ProSelection algorithm, protein structures of "weak selectors" are filtered out
      whereas structures of "strong selectors" are kept. Specifically, the structure
      which has a good statistical performance of distinguishing active ligands from
      inactive ligands is defined as a strong selector. In this study, 249 protein
      structures of 14 autophagy-related targets are investigated. Surflex-dock was
      used as the docking engine to distinguish active and inactive compounds against
      these protein structures. Both t test and Mann-Whitney U test were used to
      distinguish the strong from the weak selectors based on the normality of the
      docking score distribution. The suggested docking score threshold for active
      ligands (SDA) was generated for each strong selector structure according to the
      receiver operating characteristic (ROC) curve. The performance of ProSelection
      was further validated by predicting the potential off-targets of 43 U.S. Federal
      Drug Administration approved small molecule antineoplastic drugs. Overall,
      ProSelection will accelerate the computational work in protein structure
      selection and could be a useful tool for molecular docking, target prediction,
      and protein-chemical database establishment research.

PMID- 29016127
TI  - Aluminum Induces Distinct Changes in the Metabolism of Reactive Oxygen and
      Nitrogen Species in the Roots of Two Wheat Genotypes with Different Aluminum
      Resistance.
AB  - Aluminum (Al) toxicity in acid soils is a primary factor limiting plant growth
      and crop yield worldwide. Considerable genotypic variation in resistance to Al
      toxicity has been observed in many crop species. In wheat (Triticum aestivum L.),
      Al phytotoxicity is a complex phenomenon involving multiple physiological
      mechanisms which are yet to be fully characterized. To elucidate the
      physiological and molecular basis of Al toxicity in wheat, we performed a
      detailed analysis of reactive oxygen species (ROS) and reactive nitrogen species
      (RNS) under Al stress in one Al-tolerant (Jian-864) and one Al-sensitive (Yang-5)
      genotype. We found Al induced a significant reduction in root growth with the
      magnitude of reduction always being greater in Yang-5 than in Jian-864. These
      reductions were accompanied by significant differences in changes in antioxidant
      enzymes and the nitric oxide (NO) metabolism in these two genotypes. In the Al
      sensitive genotype Yang-5, Al induced a significant increase in ROS, NO,
      peroxynitrite (ONOO-) and activities of NADPH oxidase, peroxidase, and S
      nitrosoglutathione reductase (GSNOR). A concomitant reduction in glutathione and
      increase in S-nitrosoglutathione contents was also observed in Yang-5. In
      contrast, the Al-tolerant genotype Jian-864 showed lower levels of lipid
      peroxidation, ROS and RNS accumulation, which was likely achieved through the
      adjustment of its antioxidant defense system to maintain redox state of the cell.
      These results indicate that Al stress affected redox state and NO metabolism and
      caused nitro-oxidative stress in wheat. Our findings suggest that these molecules
      could be useful parameters for evaluating physiological conditions in wheat and
      other crop species under adverse conditions.

PMID- 29016128
TI  - Acute Toxicity, Teratogenic, and Estrogenic Effects of Bisphenol A and Its
      Alternative Replacements Bisphenol S, Bisphenol F, and Bisphenol AF in Zebrafish
      Embryo-Larvae.
AB  - Bisphenol A (BPA), a chemical incorporated into plastics and resins, has
      estrogenic activity and is associated with adverse health effects in humans and
      wildlife. Similarly structured BPA analogues are widely used but far less is
      known about their potential toxicity or estrogenic activity in vivo. We undertook
      the first comprehensive analysis on the toxicity and teratogenic effects of the
      bisphenols BPA, BPS, BPF, and BPAF in zebrafish embryo-larvae and an assessment
      on their estrogenic mechanisms in an estrogen-responsive transgenic fish
      Tg(ERE:Gal4ff)(UAS:GFP). The rank order for toxicity was BPAF > BPA > BPF > BPS.
      Developmental deformities for larval exposures included cardiac edema, spinal
      malformation, and craniofacial deformities and there were distinct differences in
      the effects and potencies between the different bisphenol chemicals. These
      effects, however, occurred only at concentrations between 1.0 and 200 mg/L which
      exceed those in most environments. All bisphenol compounds induced estrogenic
      responses in Tg(ERE:Gal4ff)(UAS:GFP) zebrafish that were inhibited by coexposure
      with ICI 182 780, demonstrating an estrogen receptor dependent mechanism. Target
      tissues included the heart, liver, somite muscle, fins, and corpuscles of
      Stannius. The rank order for estrogenicity was BPAF > BPA = BPF > BPS.
      Bioconcentration factors were 4.5, 17.8, 5.3, and 0.067 for exposure
      concentrations of 1.0, 1.0, 0.10, and 50 mg/L for BPA, BPF, BPAF, and BPS,
      respectively. We thus show that these BPA alternatives induce similar toxic and
      estrogenic effects to BPA and that BPAF is more potent than BPA, further
      highlighting health concerns regarding the use of BPA alternatives.

PMID- 29016129
TI  - Estimating the Quantity of Wind and Solar Required To Displace Storage-Induced
      Emissions.
AB  - The variable and nondispatchable nature of wind and solar generation has been
      driving interest in energy storage as an enabling low-carbon technology that can
      help spur large-scale adoption of renewables. However, prior work has shown that
      adding energy storage alone for energy arbitrage in electricity systems across
      the U.S. routinely increases system emissions. While adding wind or solar reduces
      electricity system emissions, the emissions effect of both renewable generation
      and energy storage varies by location. In this work, we apply a marginal
      emissions approach to determine the net system CO2 emissions of colocated or
      electrically proximate wind/storage and solar/storage facilities across the U.S.
      and determine the amount of renewable energy required to offset the CO2 emissions
      resulting from operation of new energy storage. We find that it takes between
      0.03 MW (Montana) and 4 MW (Michigan) of wind and between 0.25 MW (Alabama) and
      17 MW (Michigan) of solar to offset the emissions from a 25 MW/100 MWh storage
      device, depending on location and operational mode. Systems with a realistic
      combination of renewables and storage will result in net emissions reductions
      compared with a grid without those systems, but the anticipated reductions are
      lower than a renewable-only addition.

PMID- 29016130
TI  - Comparative Human Toxicity Impact of Electricity Produced from Shale Gas and
      Coal.
AB  - The human toxicity impact (HTI) of electricity produced from shale gas is lower
      than the HTI of electricity produced from coal, with 90% confidence using a Monte
      Carlo Analysis. Two different impact assessment methods estimate the HTI of shale
      gas electricity to be 1-2 orders of magnitude less than the HTI of coal
      electricity (0.016-0.024 DALY/GWh versus 0.69-1.7 DALY/GWh). Further, an
      implausible shale gas scenario where all fracturing fluid and untreated produced
      water is discharged directly to surface water throughout the lifetime of a well
      also has a lower HTI than coal electricity. Particulate matter dominates the HTI
      for both systems, representing a much larger contribution to the overall toxicity
      burden than VOCs or any aquatic emission. Aquatic emissions can become larger
      contributors to the HTI when waste products are inadequately disposed or there
      are significant infrastructure or equipment failures. Large uncertainty and lack
      of exposure data prevent a full risk assessment; however, the results of this
      analysis provide a comparison of relative toxicity, which can be used to identify
      target areas for improvement and assess potential trade-offs with other
      environmental impacts.

PMID- 29016131
TI  - Metabolites from the Plant Endophytic Fungus Aspergillus sp. CPCC 400735 and
      Their Anti-HIV Activities.
AB  - Thirty-three metabolites including five phenalenone derivatives (1-5), seven
      cytochalasins (6-12), thirteen butenolides (13-25), and eight phenyl derivatives
      (26-33) were isolated from Aspergillus sp. CPCC 400735 cultured on rice. The
      structures of all compounds were elucidated by NMR, MS, and CD experiments, of
      which 1-5 (asperphenalenones A-E), 6 (aspochalasin R), and 13 (aspulvinone R)
      were identified as new compounds. Specifically, asperphenalenones A-E (1-5)
      represent an unusual structure composed of a linear diterpene derivative linked
      to a phenalenone derivative via a C-C bond. Compounds 1, 4, 10, and 26 exhibited
      anti-HIV activity with IC50 values of 4.5, 2.4, 9.2, and 6.6 MUM, respectively
      (lamivudine 0.1 MUM; efavirenz, 0.4 * 10-3 MUM).

PMID- 29016132
TI  - Toward Understanding Mcl-1 Promiscuous and Specific Binding Mode.
AB  - Mcl-1, which is an anti-apoptotic member of the Bcl-2 protein family, is
      overexpressed in various cancers and promotes the aberrant survival of tumor
      cells. To inhibit Mcl-1, and initiate apoptosis, an interaction between BH3-only
      proteins and Mcl-1 anti-apoptotic protein is necessary. These protein-protein
      interactions exhibit some selectivity: Mcl-1 binds specifically to Noxa, whereas
      Bim and Puma bind strongly to all anti-apoptotic proteins. Even if the three
      dimensional (3D) structures of several Mcl-1/BH3-only complexes have been solved,
      the BH3-only binding specificity to Mcl-1 is still not completely understood. In
      this study, molecular dynamics simulations were used to elucidate the molecular
      basis of the interactions with Mcl-1. Our results corroborate the importance of
      four conserved hydrophobic residues and a conserved aspartic acid on BH3-only as
      a common binding pattern. Furthermore, our results highlight the contribution of
      the fifth hydrophobic residue in the C-terminal part and a negatively charged
      patch in the N-terminal of BH3-only peptides as important for their fixation to
      Mcl-1. We hypothesize that this negatively charged patch will be an Mcl-1
      specific binding pattern.

PMID- 29016133
TI  - Infrared Spectroscopy and X-ray Diffraction Characterization of Dimorphic
      Crystalline Structures of Polyethylenes with Halogens Placed at Equal Distance
      along the Backbone.
AB  - Polyethylenes with halogens placed on each and every 21st, 15th, or ninth
      backbone carbon display crystallization patterns enabled by the size of the
      halogen and by changing crystallization kinetics. The different structures have
      been identified from X-ray patterns combined with a detailed analysis of the
      infrared spectra of series containing F, Cl, or Br atoms that were either fast or
      isothermally crystallized from the melt. Under both crystallization modes, all
      specimens develop layered crystallites that accommodate 5-9 repeating units along
      the chain's axis. The size of the halogen and intermolecular staggering to
      maximize packing symmetry are responsible for striking structural differences
      observed between the series and between the two modes of crystallization. While
      the small size of the F atom causes a small perturbation to the crystal lattice
      and the orthorhombic structure is maintained for all members of the series either
      fast or isothermally crystallized, each Cl or Br-containing system presents
      dimorphism. Under fast crystallization, Cl and Br containing samples adopt the
      all-trans conformation (planar Form I), while in slowly crystallized samples
      gauche conformers set for bonds of the backbone carbons adjacent to the carbon
      with the halogen due to a close intermolecular staggering of halogens
      (herringbone Form II). In both forms the methylene sequence between halogens
      maintains the all-trans conformation. The structural details are extracted from
      the analysis of the C-halogen stretching region of the IR spectra, and from
      adherence to the n-alkane behavior of CH2 rocking, CH2 wagging, and C-C
      stretching progression modes.

PMID- 29016134
TI  - Palladium-Catalyzed Direct C(sp2)-H ortho-Arylation of Anilides Using 2
      Aminophenylpyrazole as the Directing Group.
AB  - Palladium-catalyzed ortho-arylation of anilides was achieved using 2-aminophenyl
      1H-pyrazole (2-APP) as a new directing group. Using Pd(OAc)2 as the catalyst and
      AgO as the promoter, mono- and diarylation of anilides were realized in up to 89%
      isolated yield. Further manipulation of the arylation product may be accomplished
      by a 2-step sequence involving an acidic hydrolysis of the methylated amide. More
      interestingly, in the presence of K2CO3, tandem C-C/C-N cyclization products were
      obtained for a couple of substrates.

PMID- 29016135
TI  - Charge Transport in Electronic-Ionic Composites.
AB  - Composite electrodes consisting of cathode particles and an ion-conducting phase
      can address the limited ion accessibility of the cathode in high-energy all-solid
      state lithium batteries. In this Letter, we discuss the microstructure
      conductivity relationship in an electronic-ionic composite with a focus on
      lithium ion conductivity. This study is the first step toward further
      understanding of electrochemical reactions in all solid multiphase systems.

PMID- 29016136
TI  - Specific Unbinding Forces Between Mutated Human P-Selectin Glycoprotein Ligand-1
      and Viral Protein-1 Measured Using Force Spectroscopy.
AB  - Protein tyrosine sulfation (PTS) is a key modulator of extracellular protein
      protein interaction (PPI), which regulates principal biological processes. For
      example, the capsid protein VP1 of enterovirus 71 (EV71) specifically interacts
      with sulfated P-selectin glycoprotein ligand-1 (PSGL-1) to facilitate virus
      invasion. Currently available methods cannot be used to directly observe PTS
      induced PPI. In this study, atomic force microscopy was used to measure the
      interaction between sulfated or mutated PSGL-1 and VP1. We found that the binding
      strength increased by 6.7-fold following PTS treatment on PSGL-1 with a specific
      antisulfotyrosine antibody. Similar results were obtained when the
      antisulfotyrosine antibody was replaced with the VP1 protein of EV71; however,
      the interaction forces of VP1 were only approximately one-third of those of the
      antisulfotyrosine antibody. We also found that PTS on the tyrosine-51 residue of
      glutathione S-transferases fusion-PSGL-1 was mainly responsible for the PTS
      induced PPI. Our results contribute to the fundamental understanding of PPI
      regulated through PTS.

PMID- 29016137
TI  - Efficient Singlet Oxygen Generation in Metal Nanoclusters for Two-Photon
      Photodynamic Therapy Applications.
AB  - The generation of singlet oxygen (1O2) has been established as the principal
      mechanism of photodynamic therapy (PDT). Various dyes, metal nanoparticles, and
      clusters have been shown to sensitize 1O2. However, metal nanoclusters are even
      more promising candidates as photosensitizers for this purpose. By understanding
      the optical properties that lead to efficient 1O2 generation, one can fully
      realize their potential as PDT photosensitizers. Three different metal
      nanoclusters, Au25, Ag32, and Au144, are investigated for their 1O2 generation
      efficiency. The Au144 showed a 1O2 generation rate that is 2 orders of magnitude
      higher than that for Au25 and Ag32, and several orders of magnitude higher than
      nanoparticles (>5 nm) due to Au144's high absorption cross section-to-volume
      ratio. The effectiveness of PDT in live cells with nanoclusters was demonstrated
      by two-photon excitation compared to one-photon excitation. The implication of
      these results points toward new efficient two-photon 1O2 sensitizers for
      photodynamic therapy.

PMID- 29016138
TI  - Does Metal Ion Complexation Make Radical Clocks Run Fast? An Experimental
      Perspective.
AB  - The rate constant for the beta-scission of the cumyloxyl radical (kbeta) was
      measured in the presence of various added electrolytes in acetonitrile and DMSO
      solvent. The results show that in CH3CN, kbeta increases in the presence of added
      electrolyte, roughly paralleling the size of the cation: Li+ > Mg2+ ~ Na+ >
      nBu4N+ > no added electrolyte. As suggested by Bietti et al. earlier, this effect
      is attributable to stabilizing ion-dipole interactions in the transition state of
      the developing carbonyl group, a conclusion further amplified by MO calculations
      (gas phase) reported herein. Compared to the gas phase predictions, however, this
      effect is seriously attenuated in solution because complexation of the cation to
      the electrophilic alkoxyl radical (relative to the solvent, CH3CN) is very weak.
      Because the interaction of Li+ and Na+ is much stronger with DMSO than with
      CH3CN, addition of these ions has no effect on the rate of beta-scission.

PMID- 29016139
TI  - Aryltrimethylstannane Cation Radical Fragmentation Selectivities That Depend on
      Codonor: Evidence for Reactions from Heterodimer Cation Radicals.
AB  - The aryl/methyl fragmentation selectivities for the photooxidations of
      phenyltrimethylstannane and (4-methylphenyl)trimethylstannane by 1,2,4,5
      tetracyanobenzene in acetonitrile were found to depend on the codonor used to
      generate the stannane cation radical intermediates. The aryl/methyl fragmentation
      selectivities for phenyltrimethylstannane and (4-methylphenyl)trimethylstannane
      varied by factors of 26 and 5.6, respectively, depending on the structures of the
      codonors. The fragmentation selectivities could be correlated with the oxidation
      potentials of the codonors and their steric bulk. The results can be interpreted
      by the intermediacy of heterodimer cation radicals formed between the stannane
      cation radicals and the neutral codonors, which thereby affect the fragmentation
      selectivities.

PMID- 29016140
TI  - Theoretical Study on the Kinetics of Thermal Decomposition of Guaiacol and
      Catechol.
AB  - The theoretical aspects of the development of a chemical kinetic model for
      guaiacol and catechol pyrolysis are presented to describe the pyrolysis behaviors
      of the individual lignin-derived components. The possible pyrolysis pathways
      involving both unimolecular and bimolecular decomposition were investigated by
      the potential energy surfaces (PES) calculated at CBS-QB3 level. The high
      pressure limiting rate constants of each elementary reaction step were evaluated
      based on the transition state theory (TST) to determine the dominant pyrolysis
      pathways. The kinetic analysis results predicted the most favorable catechol
      unimolecular decomposition pathways, where catechol isomerization to 2
      hydroxycyclohexa-2,4-dien-1-one occurred via migration of the hydroxyl H atom,
      followed by decomposition into 1,3-cyclobutadiene, acetylene, and CO. In the case
      of the bimolecular reaction of catechol, a hydrogen radical is coupled to the
      carbon atom in the benzene ring, leading to the formation of phenol and a
      hydroxyl radical through dehydroxylation. On the other hand, guaiacol is likely
      to form catechol and phenol via the O-CH3 homolysis and coupling of a hydrogen
      radical to the carbon atom with the methoxyl group, respectively.

PMID- 29016141
TI  - X-ray and Neutron Reflectivity Study Shows That CLIC1 Undergoes Cholesterol
      Dependent Structural Reorganization in Lipid Monolayers.
AB  - CLIC1 belongs to the ubiquitous family of chloride intracellular ion channel
      proteins that are evolutionarily conserved across species. The CLICs are unusual
      in that they exist mainly as soluble proteins but possess the intriguing property
      of spontaneous conversion from the soluble to an integral membrane-bound form.
      This conversion is regulated by the membrane lipid composition, especially by
      cholesterol, together with external factors such as oxidation and pH. However,
      the precise physiological mechanism regulating CLIC1 membrane insertion is
      currently unknown. In this study, X-ray and neutron reflectivity experiments were
      performed to study the interaction of CLIC1 with different phospholipid
      monolayers prepared using POPC, POPE, or POPS with and without cholesterol in
      order to better understand the regulatory role of cholesterol in CLIC1 membrane
      insertion. Our findings demonstrate for the first time two different structural
      orientations of CLIC1 within phospholipid monolayers, dependent upon the absence
      or presence of cholesterol. In phospholipid monolayers devoid of cholesterol,
      CLIC1 was unable to insert into the lipid acyl chain region. However, in the
      presence of cholesterol, CLIC1 showed significant insertion within the
      phospholipid acyl chains occupying an area per protein molecule of 6-7 nm2 with a
      total CLIC1 thickness ranging from ~50 to 56 A across the entire monolayer. Our
      data strongly suggests that cholesterol not only facilitates the initial docking
      or binding of CLIC1 to the membrane but also promotes deeper penetration of CLIC1
      into the hydrophobic tails of the lipid monolayer.

PMID- 29016142
TI  - Charging and Aggregation Behavior of Cellulose Nanofibers in Aqueous Solution.
AB  - To understand the charging and aggregation of cellulose nanofibers (CNFs), we
      performed the following experimental and theoretical studies. The charging
      behavior of CNFs was characterized by potentiometric acid-base titration
      measuring the density of deprotonated carboxyl groups at different KCl
      concentrations. The charging behavior from the titration was quantitatively
      described by the 1-pK Poisson-Boltzmann (PB) model for a cylinder. The
      electrophoretic mobility of CNFs was measured as a function of pH by
      electrophoretic light scattering. The mobility was analyzed with the equation for
      an infinitely long cylinder considering the relaxation of the electric double
      layer. Good agreement between experimental mobilities and theoretical calculation
      was obtained by assuming a reasonable distance from the surface to the slipping
      plane. The result demonstrated that the negative charge of CNFs originates from
      the deprotonation of beta(1-4)-d-glucuronan on the surface. The aggregation
      behavior of CNFs was studied by measuring the hydrodynamic diameter of CNFs at
      different pH and KCl concentrations. Also, we calculated the capture efficiencies
      of aggregation, using interaction energies of perpendicularly and parallelly
      oriented cylinders. The interaction energies between cylinders in both
      orientations were obtained by the Derjaguin, Landau, Verwey, and Overbeek theory,
      where the electrostatic repulsion was calculated from the surface potential
      obtained by the 1-pK PB model. From comparison of the theoretical capture
      efficiency with the measured hydrodynamic diameter, we suggest that CNFs can be
      aggregated in perpendicular orientation at low pH and low salt concentration, and
      the fast aggregation regime of CNFs is realized by the reduction of electric
      repulsion for both perpendicularly and parallelly interacting CNFs. Meanwhile,
      the application of Smoluchowski's equation to the mobility of CNFs results in the
      underestimation of the zeta potential.

PMID- 29016143
TI  - Nuclear and Fluorescent Labeled PD-1-Liposome-DOX-64Cu/IRDye800CW Allows Improved
      Breast Tumor Targeted Imaging and Therapy.
AB  - The overexpression of programmed cell death-1 (PD-1) in tumors as breast cancer
      makes it a possible target for cancer imaging and therapy. Advances in molecular
      imaging, including radionuclide imaging and near-infrared fluorescence (NIRF)
      imaging, enable the detection of tumors with high sensitivity. In this study, we
      aim to develop a novel PD-1 antibody targeted positron emission tomography (PET)
      and NIRF labeled liposome loaded with doxorubicin (DOX) and evaluate its
      application for in vivo cancer imaging and therapy. IRDye800CW and 64Cu were
      conjugated to liposomes with PD-1 antibody labeling, and DOX was inside the
      liposomes to form theranostic nanoparticles. The 4T1 tumors were successfully
      visualized with PD-1-Liposome-DOX-64Cu/IRDye800CW using NIRF/PET imaging. The
      bioluminescent imaging (BLI) results showed that tumor growth was significantly
      inhibited in the PD-1-Liposome-DOX-treated group than the IgG control. Our
      results highlight the potential of using dual-labeled theranostic PD-1 mAb
      targeted Liposome-DOX-64Cu/IRDye800CW for the management of breast tumor.

PMID- 29016144
TI  - Alismanin A, a Triterpenoid with a C34 Skeleton from Alisma orientale as a
      Natural Agonist of Human Pregnane X Receptor.
AB  - Alismanin A (1), a novel aromatic triterpenoid with a C34 skeleton, was isolated
      from Alisma orientale together with a rearranged nor-triterpenoid (2) and a 13,17
      seco triterpenoid (3). Their structures were determined by a combination of
      HRESIMS, 2D NMR spectra, electronic circular dichroism (ECD), theoretical
      calculations, and X-ray diffraction analysis. Compounds 1 and 2 displayed
      significant activation effects on pregnane X receptor (PXR) at 10 nM. A plausible
      biosynthetic pathway for 1-3 is also discussed.

PMID- 29016145
TI  - Terahertz Detection and Imaging Using Graphene Ballistic Rectifiers.
AB  - A graphene ballistic rectifier is used in conjunction with an antenna to
      demonstrate a rectenna as a terahertz (THz) detector. A small-area (<1 MUm2)
      local gate is used to adjust the Fermi level in the device to optimize the output
      while minimizing the impact on the cutoff frequency. The device operates in both
      n- and p-type transport regimes and shows a peak extrinsic responsivity of 764
      V/W and a corresponding noise equivalent power of 34 pW Hz-1/2 at room
      temperature with no indications of a cutoff frequency up to 0.45 THz. The device
      also demonstrates a linear response for more than 3 orders of magnitude of input
      power due to its zero threshold voltage, quadratic current-voltage
      characteristics and high saturation current. Finally, the device is used to take
      an image of an optically opaque object at 0.685 THz, demonstrating potential in
      both medical and security imaging applications.

PMID- 29016146
TI  - Effect of Aldehyde and Carboxyl Functionalities on the Surface Chemistry of
      Biomass-Derived Molecules.
AB  - The adsorption and decomposition of acetaldehyde and acetic acid were studied on
      Rh(100) to gain insight into the interaction of aldehyde and carboxyl groups of
      biomass-derived molecules with the surface. Temperature-programmed reaction
      spectroscopy (TPRS) was used to monitor gaseous reaction products, whereas
      Reflection absorption infrared spectroscopy (RAIRS) was used to determine the
      nature of surface intermediates and reaction paths. The role of adsorbate
      interactions in oxygenate decomposition chemistry was also investigated by
      varying the surface coverage. Acetaldehyde adsorbs in an eta2(C, O) configuration
      for all coverages, where the carbonyl group binds to the surface via the C and O
      atoms. Decomposition occurs below room temperature (180-280 K) via C-H and C-C
      bond breaking, which releases CO, H, and CHx species on the surface. At low
      coverage, CHx dehydrogenation dominates and surface carbon is produced alongside
      H2 and CO. At high coverage, about 60% of the CHx hydrogenates to form methane,
      whereas only 40% of the CHx decomposes further to surface carbon. Acetic acid
      adsorbs dissociatively on the Rh(100) surface via O-H bond scission, forming a
      mixture of mono- and bidentate acetate. The decomposition of acetate proceeds via
      two different pathways: (i) deoxygenation via C-O and C-C bond scissions and (ii)
      decarboxylation via C-C bond scission. At low coverage, the decarboxylation
      pathway dominates, a process that occurs at slightly above room temperature (280
      360 K) and produces CO2 and CHx, where the latter decomposes further to surface
      carbon and H2. At high coverage, both decarboxylation and deoxygenation occur,
      slightly, above room temperature (280-360 K). The resulting O adatoms produced in
      the deoxygenation path react with surface hydrogen or CO to form water and CO2,
      respectively. The CHx species dehydrogenate to surface carbon for all coverages.
      Our findings suggest that oxygenates with a C?O functionality and an alkyl end
      react on the Rh(100) surface to produce synthesis gas and small hydrocarbons
      whereas CO2 and synthesis gas are produced when oxygenates with a COOH
      functionality and an alkyl end react with the Rh(100) surface. For both cases,
      carbon accumulation occurs on the surface.

PMID- 29016147
TI  - Self-Assembly of Long-Chain Betaine Surfactants: Effect of Tailgroup Structure on
      Wormlike Micelle Formation.
AB  - Long-chain amidopropyl betaines are known for their ability to self-assemble into
      viscoelastic wormlike micellar structures. Here, we explore the effect of
      tailgroup molecular architecture on this process, comparing five molecules, each
      with C18 chains but different levels of unsaturation and branching. The
      surfactants are synthesized from stearic, oleic, linoleic, linolenic, and
      isostearic acids. The self-assembly of these molecules in aqueous solutions is
      explored using small- and ultra-small-angle neutron scattering (SANS and USANS).
      It is seen that optimum wormlike micelle formation is achieved for the oleic
      chained surfactant, and the alignment of self-assembled structures is further
      explored using rheo-SANS. The more highly unsaturated molecules form rodlike
      micelles, whereas the stearic-tailed molecule shows a pronounced Krafft point and
      the isostearic-chained surfactant is entirely water-insoluble. These results
      demonstrate the critical importance of tailgroup geometry on surfactant
      properties and self-assembly for this industrially important class of
      surfactants.

PMID- 29016148
TI  - Receding Contact Line Motion on Nanopatterned and Micropatterned Polymer
      Surfaces.
AB  - Surface properties such as topography and chemistry affect the motion of the
      three-phase contact line (solid/liquid/air), which in turn affects the contact
      angle of a liquid moving on a solid surface. In this work, the motion of the
      receding water contact line was studied on chemically and topographically
      patterned surfaces obtained from the dewetting of thin polymer films. The
      patterned surfaces consisted of hydrophilic poly(4-vinylpyridine) (P4VP) bumps,
      which were either microsized and sparse or nanosized and dense, on top of a
      hydrophobic polystyrene (PS) background layer. These patterns are designed for
      atmospheric water capture, for which the easy roll off of water droplets is
      crucial to their efficient performance. The dynamic receding water contact angle
      and contact line height of the patterned surfaces were measured by vertically
      withdrawing the surfaces from a water bath and compared to those of a flat P4VP
      substrate. For both the micropatterned and nanopatterned surfaces, the height of
      the dynamic contact lines normalized by the capillary length was characterized by
      the equilibrium limit that was predicted from static states. The nanopatterned
      surface had a faster increase in the normalized height as the capillary number
      increased. The dynamic receding contact angles on all surfaces studied decreased
      with increasing withdrawing velocity. Surprisingly, even for these patterned
      surfaces with high hysteresis, the dynamic receding contact angle followed the
      Cox-Voinov relation at capillary numbers of between 1 * 10-5 and 5 * 10-5.

PMID- 29016150
TI  - Imagine that! The effect of counterstereotypic imagined intergroup contact on
      weight bias.
AB  - OBJECTIVE: Higher body-weight people are highly stigmatized and face prejudice
      and discrimination across a number of domains. Further, experiences of weight
      stigmatization are associated with a host of negative physical, psychological,
      and social consequences. However, less is known about effective means for
      reducing weight bias. One strategy that has shown some success in prejudice
      reduction, yet is relatively untested for weight bias, is imagined intergroup
      contact. The purpose of this study was to investigate the effect of
      counterstereotypic imagined intergroup contact on weight bias. METHOD:
      Participants were randomly assigned to 1 of 2 experimental conditions or a
      control group. In the experimental conditions, participants were asked to imagine
      interactions with either a counterstereotypic (e.g., confident, attractive) or
      stereotypic (e.g., unattractive, insecure) "obese" person. Participants then
      completed the Anti-fat Attitudes Questionnaire (dislike subscale; Crandall, 1994;
      Quinn & Crocker, 1999), the Universal Measure of Bias-Fat (negative judgment and
      social distance subscales; Latner et al., 2008), and the Fat Phobia Scale.
      RESULTS: Results indicated that participants in the counterstereotypic condition
      reported lower levels of weight bias (dislike, negative judgment, and social
      distance) than participants in the stereotypic and control conditions.
      CONCLUSION: These findings highlight the potential usefulness of
      counterstereotypic imagined contact to reduce weight bias. (PsycINFO Database
      Record

PMID- 29016149
TI  - Physical activity and negative affective reactivity in daily life.
AB  - OBJECTIVE: The results from experimental studies indicate that physically active
      individuals remain calmer and report less anxiety after the induction of a
      standardized stressor. The current study extends this research to real life, and
      examines whether daily physical activity attenuates negative affect that occurs
      in response to naturally occurring daily stressors. METHOD: The current study
      used data from the second wave of the National Study of Daily Experiences, a sub
      study of the second wave of the Midlife in the United States Study (MIDUS-II) of
      2,022 individuals aged 33-84 questioned nightly for eight consecutive days about
      their general affect and affective responses to stressful events and their
      engagement in physical activity. RESULTS: Results indicated that while negative
      affect is significantly elevated on days with stressful events compared to days
      free of events in all individuals, these effects are attenuated in those who
      remain physically active when compared to those who were underactive. This was
      also true for any day participants were physically active. Importantly, negative
      affect in response to any specific stressor was reduced the closer in time that
      the stressor occurred to the bout of exercise in underactive participants, while,
      in active participants, negative affect in response to any stressor remained low
      throughout the entire day that participants reported that they were active.
      CONCLUSION: Given the significant mental and physical health implications of
      elevated affective reactivity observed in previous studies, the current study
      sheds further light on the importance of remaining physically active in times of
      stress. (PsycINFO Database Record

PMID- 29016151
TI  - Associations between immigrant status and pharmacological treatments for diabetes
      in U.S. adults.
AB  - OBJECTIVES: Although treatment disparities in diabetes have been documented along
      racial/ethnic lines, it is unclear if immigrant groups in the United States
      experience similar treatment disparities. Our objective was to determine whether
      immigrant status is associated with differences in pharmacological treatment of
      diabetes in a nationally representative sample of adults with diabetes. We were
      specifically interested in differences in treatment with oral hypoglycemic agents
      (OHA) and insulin. METHOD: Respondents were 2,260 adults from National Health and
      Nutritional Examination Survey (NHANES) 2003-2012 with a self-reported diabetes
      diagnosis. Immigrant status was indicated by birth within (U.S.-born) or outside
      (foreign-born) the 50 U.S. States or Washington, DC. Multinomial logistic
      regression analyses examined associations between immigrant status and (a)
      treatment with OHAs only and (b) treatment with insulin only or insulin and OHA
      combination therapy, using no treatment as the reference group. RESULTS:
      Adjusting for demographics, diabetes severity and duration, cardiovascular
      disease (CVD), and CVD risk factors, being foreign-born versus U.S.-born was not
      associated with treatment with OHAs only (odds ratio [OR] = 1.59; 95% confidence
      interval [CI] [0.97, 2.60]). However, being foreign-born was associated with
      decreased odds (OR = 0.53; 95% CI [0.28, 0.99]) of treatment with insulin.
      CONCLUSIONS: Pharmacological treatment of diabetes differs along immigrant status
      lines. To understand these findings, studies capturing the processes underlying
      treatment differences in diabetes among immigrants are needed. Findings raise the
      possibility that integrating information about a patient's immigrant status, in
      addition to racial/ethnic identity, may be an important component of culturally
      sensitive diabetes care. (PsycINFO Database Record

PMID- 29016152
TI  - Knowingly but naively: The overpowering influence of innocence on interrogation
      rights decision-making.
AB  - Most suspects waive the guaranteed protections that interrogation rights afford
      them against police intimidation. One factor thought to motivate suspects'
      inclination to waive their rights stems from the acquiescence bias whereby
      suspects mindlessly comply with interrogators' requests. However, research
      bearing on the phenomenology of innocence has demonstrated the power of
      innocents' mindset, which could motivate some innocent suspects to waive their
      rights knowingly (instead of mindlessly complying). To test these ideas,
      participants (N = 178) were (a) rightfully (guilty) or wrongfully (innocent)
      accused of wrongdoing during an experimental session, (b) administered 1 of 2
      forms that by signing either waived or invoked their rights to a student
      advocate, and (c) given questions to assess their degree of knowing during the
      decision-making process (i.e., extent to which individuals were cognizant of
      their decisions). Results demonstrated that unknowing innocent and guilty
      individuals tended to passively comply, engaging in a pre-interrogation
      acquiescence bias by signing waive and invoke forms at similar rates. But, as
      participants became more cognizant of their decisions, they acquiesced at lower
      rates and their change from acquiescence differed depending on their status. As
      innocents became more cognizant, they signed the waiver form at higher rates than
      the invoke form, thereby demonstrating that innocence can motivate some suspects
      to knowingly forgo their rights. Conversely, as guilty individuals became more
      cognizant, they signed the invoke form at higher rates than the waiver form.
      These findings have implications for reforming pre-interrogation protocols,
      protecting suspects' civil liberties, and preventing innocents from offering
      false self-incriminating evidence. (PsycINFO Database Record

PMID- 29016153
TI  - The implementation and effect of trauma-informed care within residential youth
      services in rural Canada: A mixed methods case study.
AB  - OBJECTIVE: The prevalence and associated risks of trauma have led youth-serving
      institutions to adopt trauma-informed care (TIC). A limited research base has
      linked TIC with improved outcomes. Associations between TIC and vicarious
      traumatization (VT) are even less commonly studied. The purpose of this case
      study is to evaluate the implementation and effect of TIC within 1 residential
      youth services division in rural Canada using the curriculum-based Risking
      Connection (RC; Saakvitne et al., 2001) and Restorative Approach (RA; Wilcox,
      2012) trauma training programs, with a focus on VT. METHOD: We used an
      explanatory sequential mixed methods design and a participatory action research
      approach to evaluate the implementation and effect of RC and RA. Study 1, the
      quantitative program evaluation, used a prepost design to evaluate the effect of
      RC and RA on staff. Study 2, the qualitative study, used participant observations
      and interviews to develop a deeper understanding the quantitative findings.
      RESULTS: This study replicated previous findings that RC improves attitudes
      favorable to TIC but found that staff experience of VT increased after TIC
      training. Qualitative findings suggested that the division was successfully
      implementing TIC and that increased awareness and discussion of VT were
      potentially responsible for increases in VT scores. CONCLUSIONS: This case study
      documents improvements in staff attitudes favorable to TIC post-RC and RA and
      presents an in-depth analysis of TIC implementation. The study also highlights
      the complicated relationship between TIC implementation and staff experience of
      VT. Finally, this study provides a blueprint for conducting program evaluations
      of TIC. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 29016154
TI  - Who helps the helper? Differentiation of self as an indicator for resisting
      vicarious traumatization.
AB  - OBJECTIVE: This study comprises a first attempt to explain and predict vicarious
      traumatization among therapists by means of Bowen's Family Systems Theory (Bowen,
      1978), especially with reference to the phenomenon "differentiation of self," a
      central feature of his theory. METHOD: A sample of 134 individual and group
      therapists who work in public and private clinics completed a series of
      questionnaires that provided data regarding demographic information,
      differentiation of self, and a belief scale that measures the existence of
      vicarious trauma. RESULTS: The findings indicate a strong negative correlation
      between vicarious traumatization and differentiation of self. In addition,
      participant age and "being in therapy" were both found to correlate with
      differentiation of self and vicarious traumatization. CONCLUSION: These findings
      point to the importance of differentiation of self as a resilience factor
      protecting against vicarious trauma, and have the potential to contribute to the
      development of tools for efficiently and accurately assessing predisposition
      toward vicarious traumatization among therapists. (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 29016155
TI  - Association of posttraumatic nightmares and psychopathology in a military sample.
AB  - OBJECTIVE: Nightmares are among the most frequent and disturbing symptoms of
      posttraumatic stress disorder (PTSD). However, basic research questions regarding
      key associations between certain nightmare characteristics, especially
      replicativeness, and posttraumatic psychopathology need further empirical
      elaboration. METHOD: Sixty-two German soldiers (mean age 33.8 years, 17.7%
      females) admitted to a hospital-based treatment program for veterans completed
      extensive assessments consisting of clinical interviews and self-rating measures
      with respect to sociodemographic characteristics and psychopathology as well as
      dream-related variables. RESULTS: Although nightmare distress, frequency, and
      replicativeness were all linked to PTSD symptomatology, only the latter proved to
      be a significant predictor of PTSD diagnosis. Moreover, none of these nightmare
      characteristics predicted a depression diagnosis. CONCLUSIONS: The
      replicativeness of nightmares appears to be a key variable for understanding the
      relationship between posttraumatic nightmares and PTSD, whereas nightmare
      frequency and distress appear to be more aptly defined as generic markers of
      mental health. (PsycINFO Database Record

PMID- 29016156
TI  - Italian validation of the Childhood Trauma Questionnaire-Short Form on a college
      group.
AB  - : The Childhood Trauma Questionnaire-Short Form (CTQ-SF) is the most widely used
      measure of childhood traumatic experiences for the retrospective assessment of
      adolescents and adults. It facilitates the detection of co-occurrence of traumas
      during childhood, in effect overcoming the lack of standardized tools for adult
      assessment. OBJECTIVE: The current study aimed to validate the Italian Childhood
      Trauma Questionnaire on college students. On this scope, we compared several
      factor structures proposed in the literature by the original authors (Bernstein
      et al., 2003), as well as in cross-cultural applications. In addition, we
      investigated psychometric properties of the Italian CTQ-SF in terms of internal
      consistency reliability and convergent validity with posttraumatic stress
      disorder and general psychopathology. METHOD: A total of 446 undergraduate
      students (M = 23 years, SD = 2.87) participated in the study. RESULTS: The
      confirmatory factor analyses indicated that the 5-factor solution represents the
      model that best fits Italian data of nonclinical samples. The unidimensionality
      of the scale was also not supported by present findings. Additionally, internal
      consistency reliability was good across the 5 scales and in line with the
      original version, as well as with previous applications. Correlation of the CTQ
      SF with posttraumatic stress disorder and general psychopathology suggested that
      current posttraumatic and general symptoms were moderately significantly
      associated with the emotional forms of childhood trauma. CONCLUSION: Findings
      highlighted reliability, structure, and concurrent validity for the Italian CTQ
      SF and thus supported the implementation of the Italian version of the Childhood
      Trauma Questionnaire-Short Form in the assessment of traumatic experiences and
      the screening in nonclinical groups. (PsycINFO Database Record

PMID- 29016157
TI  - Assailant identity and self-reported nondisclosure of military sexual trauma in
      partnered women veterans.
AB  - OBJECTIVE: Department of Veterans Affairs estimates of military sexual trauma
      (MST) suggest 27% of female veterans have experienced MST. However, Department of
      Defense data (Department of Defense, 2014) show that a subgroup of active-duty
      women do not report sexual assaults to a military authority, suggesting barriers
      to disclosure exist among military samples. No study of female veterans has
      examined rates of nondisclosure among those with previous screens for MST; these
      data could inform screening efforts and establishment of safe havens for candid
      disclosures. METHOD: Using an explanatory sequential mixed-methods survey, a
      history of MST, and postservice MST disclosures during screening and their
      associations with demographic, assault, and screening-setting characteristics
      were evaluated in 359 female veterans. Open-ended responses regarding barriers to
      disclosure were analyzed using editing analysis style. RESULTS: Eighty-one
      percent (n = 289) reported MST. Of these, 50% (n = 143) reported a prior
      screening and 25% (n = 35) reported they did not disclose their true MST status.
      Veterans who experienced MST by a unit-member assailant were significantly less
      likely to disclose (adjusted odds ratio = 4.75, 95% confidence interval = 1.20
      18.30). Disclosure barriers included stigma, experiential avoidance, and
      discomfort with the screening setting. CONCLUSION: Creative interventions to
      reduce nondisclosure among female veterans, with specific attention to those
      assaulted by a unit member, are urgently needed. (PsycINFO Database Record

PMID- 29016158
TI  - Fear, negative cognition, and depression mediate the relationship between
      traumatic exposure and sleep problems among flood victims in China.
AB  - OBJECTIVE: To examine the prerequisites of sleep problems among a traumatized
      population, and assess the underlying mechanisms of sleep problems following
      trauma. METHOD: The current study investigated 187 flood victims from 5 makeshift
      shelters in the Wuhu city of Anhui province after a major flood disaster that
      occurred in July 2016. A traumatic exposure questionnaire, a fear questionnaire,
      a posttraumatic cognition inventory, a depression inventory, and a sleep problems
      questionnaire were used. RESULTS: Traumatic exposure had a direct and positive
      association with sleep problems and could also be indirectly associated with
      sleep problems through fear, depression, but not negative cognitions. The
      positive association could be the result of a path from negative cognitions to
      depression, but not from fear to negative cognition, or from fear to depression.
      Furthermore, a threefold multipath from fear to depression via negative
      cognitions could also link traumatic exposure to sleep problems. CONCLUSIONS:
      Flood victims' sleep problems are elicited by the combined role of fear, negative
      cognitions, and depression following trauma. (PsycINFO Database Record

PMID- 29016159
TI  - An examination of the test-retest reliability of the ACE-SQ in a sample of
      college athletes.
AB  - OBJECTIVE: The Adverse Childhood Experiences (ACE) study is one of the largest
      studies ever conducted that has examined the relationship of childhood abuse,
      neglect, and family dysfunction to subsequent health and well-being later in
      life. Questions from the ACE study evolved into the ACE Study Questionnaire, a
      measure used for assessing individuals' self-reported experiences of childhood
      adversity. The ACE measure is widely available and the Centers for Disease
      Control and Prevention (CDC) recommends it as a tool for assessing one's lifetime
      risk of mental and physical health problems and other negative social problems.
      Despite the extensive dissemination of the ACE Study Questionnaire, to date there
      has been only one article published about its psychometric properties. The
      current study examined the test-retest reliability of the ACE-SQ in a sample of
      nonservice seeking college athletes (N = 141). METHOD: Time 1 and Time 2 of data
      collection were approximately one year apart. Pearson's correlations were
      computed to observe a level of agreement between Time 1 and Time 2 responses.
      RESULTS: The overall measure yielded a modest test-retest coefficient, r = .71, p
      < .001. Household dysfunction items demonstrated a higher stability coefficient,
      r = .65, p < .001 than did abuse and neglect items, r = .52, p < .001.
      CONCLUSIONS: These findings suggest that further research is needed on the
      psychometric properties of this questionnaire in different age populations.
      (PsycINFO Database Record

PMID- 29016160
TI  - Chronic pain under missile attacks: Role of pain catastrophizing, media, and
      stress-related exposure.
AB  - OBJECTIVE: We examined the effects of exposure to missile attacks on patients'
      pain and depressive symptoms, moderated by pain-related catastrophizing. METHOD:
      One-hundred Israeli chronic pain patients were assessed both prior and subsequent
      to military operation "Protective Edge," during which thousands of missiles
      landed on populated areas across the country. Baseline assessment included pain,
      depression, and catastrophizing, and postwar assessment tapped exposure to
      missiles, pain, and depression. RESULTS: Media exposure predicted an increase in
      sensory pain under high levels of catastrophizing (1 SD above the mean;
      unstandardized simple slope = 0.57, p = .01), and depression in the entire sample
      (b = 0.61, p = .01). Perceived stress related to the missiles exhibited an
      expected effect, predicting an increase in depressive symptoms (b = 1.45, p =
      .03). Unexpectedly, perceived stress predicted a decrease in sensory pain under
      high levels of catastrophizing (unstandardized simple slope = -0.49, p = .02).
      CONCLUSIONS: Media exposure to acute stress may render chronic pain patients more
      vulnerable to experiencing pain and depressive symptoms, depending on their use
      of pain-based catastrophizing. High catastrophizers may attend more to outside
      threats, amplifying the sensory and affective aspects of pain they experience.
      Perceived stress also plays a significant role in eliciting depressive symptoms
      in this population. (PsycINFO Database Record

PMID- 29016161
TI  - The jingle-jangle of work-nonwork balance: A comprehensive and meta-analytic
      review of its meaning and measurement.
AB  - We review research on work-nonwork balance to examine the presence of the jingle
      fallacy-attributing different meanings to a single construct label-and the jangle
      fallacy-using different labels for a single construct. In 290 papers, we found
      233 conceptual definitions that clustered into 5 distinct, interpretable types,
      suggesting evidence of the jingle fallacy. We calculated Euclidean distances to
      quantify the extent of the jingle fallacy and found high divergence in
      definitions across time and publication outlet. One exception was more agreement
      recently in better journals to conceptualize balance as unidimensional,
      psychological, and distinct from conflict and enrichment. Yet, over time many
      authors have committed the jangle fallacy by labeling measures of conflict and/or
      enrichment as balance, and disagreement persists even in better journals about
      the meanings attributed to balance (e.g., effectiveness, satisfaction). To
      examine the empirical implications of the jingle and jangle fallacies, we
      conducted meta-analyses of distinct operational definitions of balance with job,
      life, and family satisfaction. Effect sizes for conflict and enrichment measures
      were typically smaller than effects for balance measures, providing evidence of a
      unique balance construct that is not interchangeable with conflict and
      enrichment. To begin to remedy concerns raised by our review, we propose a
      definition of work-nonwork balance drawing from theory, empirical evidence from
      our review, and normative information about how balance should be defined. We
      conclude with a theory-based agenda for future research. (PsycINFO Database
      Record

PMID- 29016162
TI  - Do women CEOs face greater threat of shareholder activism compared to male CEOs?
      A role congruity perspective.
AB  - We examine the glass cliff proposition that female CEOs receive more scrutiny
      than male CEOs, by investigating whether CEO gender is related to threats from
      activist investors in public firms. Activist investors are extraorganizational
      stakeholders who, when dissatisfied with some aspect of the way the firm is being
      managed, seek to change the strategy or operations of the firm. Although some
      have argued that women will be viewed more favorably than men in top leadership
      positions (so-called "female leadership" advantage logic), we build on role
      congruity theory to hypothesize that female CEOs are significantly more likely
      than male CEOs to come under threat from activist investors. Results support our
      predictions, suggesting that female CEOs may face additional challenges not faced
      by male CEOs. Practical implications and directions for future research are
      discussed. (PsycINFO Database Record

PMID- 29016163
TI  - A meta-analysis of sex and race differences in perceived workplace mistreatment.
AB  - Despite the growing number of meta-analyses published on the subject of workplace
      mistreatment and the expectation that women and racial minorities are mistreated
      more frequently than men and Whites, the degree of subgroup differences in
      perceived workplace mistreatment is unknown. To address this gap in the
      literature, we meta-analyzed the magnitude of sex and race differences in
      perceptions of workplace mistreatment (e.g., harassment, discrimination,
      bullying, incivility). Results indicate that women perceive more sex-based
      mistreatment (i.e., mistreatment that explicitly targets a person's sex) in the
      workplace than men (delta = .46; k = 43), whereas women and men report comparable
      perceptions of all other forms of mistreatment (delta = .02; k = 300). Similarly,
      although racial minorities perceive more race-based mistreatment (i.e.,
      mistreatment that explicitly targets a person's race) in the workplace than
      Whites (delta = .71; k = 18), results indicate smaller race differences in all
      other forms of workplace mistreatment (delta = .10; k = 61). Results also
      indicate that sex and race differences have mostly decreased over time, although
      for some forms of mistreatment, subgroup differences have increased over time. We
      conclude by offering explanations for the observed subgroup differences in
      workplace mistreatment and outline directions for future research. (PsycINFO
      Database Record

PMID- 29016164
TI  - Linking job-relevant personality traits, transformational leadership, and job
      performance via perceived meaningfulness at work: A moderated mediation model.
AB  - By integrating the fundamental principles of the theory of purposeful work
      behavior (TPWB; Barrick, Mount, & Li, 2013) with cognitive-affective personality
      system (CAPS) theory (Mischel, 1977; Mischel & Shoda, 1995), we examine how and
      when salespeople's job-relevant personality traits relate to their performance.
      We argue that individuals with personality traits that fit outdoor sales jobs
      (i.e., conscientious, extraversion, openness to experience) will perceive their
      work as more meaningful and as a result achieve heightened performance. Moreover,
      drawing from TPWB and CAPS theory, we expect that as an important element of the
      social context, transformational leadership moderates the indirect effect of
      salespeople's job-relevant personality traits on their job performance via
      enhanced perceptions of meaningfulness at work. Results based on data from 496
      outdoor salespeople and their 218 supervisors and regional managers provide
      support for the hypotheses pertaining to conscientiousness and openness, but not
      extraversion. Specifically, the conditional indirect effects of conscientiousness
      or openness on performance through perceived meaningfulness are more positive
      under low, rather than high, levels of transformational leadership. Implications
      for research and practice are discussed along with study limitations and future
      research directions. (PsycINFO Database Record

PMID- 29016165
TI  - "Falsifiability is not optional": Correction to LeBel et al. (2017).
AB  - Reports an error in "Falsifiability is not optional" by Etienne P. LeBel, Derek
      Berger, Lorne Campbell and Timothy J. Loving (Journal of Personality and Social
      Psychology, 2017[Aug], Vol 113[2], 254-261). In the reply, there were two errors
      in the References list. The publishing year for the 14th and 21st articles was
      cited incorrectly as 2016. The in-text acronym associated with these citations
      should read instead as FER2017 and LCL2017. The correct References list citations
      should read as follows, respectively: Finkel, E. J., Eastwick, P. W., & Reis, H.
      T. (2017). Replicability and other features of a high-quality science: Toward a
      balanced and empirical approach. Journal of Personality and Social Psychology,
      113, 244-253. http://dx.doi.org/10.1037/pspi0000075 LeBel, E. P., Campbell, L., &
      Loving, T. J. (2017). Benefits of open and high-powered research outweigh costs.
      Journal of Personality and Social Psychology, 113, 230-243. http://dx.doi.org/10
      .1037/pspi0000049. The online version of this article has been corrected. (The
      following abstract of the original article appeared in record 2017-30567-003.)
      Finkel, Eastwick, and Reis (2016; FER2016) argued the post-2011 methodological
      reform movement has focused narrowly on replicability, neglecting other essential
      goals of research. We agree multiple scientific goals are essential, but argue,
      however, a more fine-grained language, conceptualization, and approach to
      replication is needed to accomplish these goals. Replication is the general
      empirical mechanism for testing and falsifying theory. Sufficiently
      methodologically similar replications, also known as direct replications, test
      the basic existence of phenomena and ensure cumulative progress is possible a
      priori. In contrast, increasingly methodologically dissimilar replications, also
      known as conceptual replications, test the relevance of auxiliary hypotheses
      (e.g., manipulation and measurement issues, contextual factors) required to
      productively investigate validity and generalizability. Without prioritizing
      replicability, a field is not empirically falsifiable. We also disagree with
      FER2016's position that "bigger samples are generally better, but . . . that very
      large samples could have the downside of commandeering resources that would have
      been better invested in other studies" (abstract). We identify problematic
      assumptions involved in FER2016's modifications of our original research-economic
      model, and present an improved model that quantifies when (and whether) it is
      reasonable to worry that increasing statistical power will engender potential
      trade-offs. Sufficiently powering studies (i.e., >80%) maximizes both research
      efficiency and confidence in the literature (research quality). Given that we are
      in agreement with FER2016 on all key open science points, we are eager to start
      seeing the accelerated rate of cumulative knowledge development of social
      psychological phenomena such a sufficiently transparent, powered, and falsifiable
      approach will generate. (PsycINFO Database Record

PMID- 29016166
TI  - "Replicability and other features of a high-quality science: Toward a balanced
      and empirical approach": Correction to Finkel et al. (2017).
AB  - Reports an error in "Replicability and other features of a high-quality science:
      Toward a balanced and empirical approach" by Eli J. Finkel, Paul W. Eastwick and
      Harry T. Reis (Journal of Personality and Social Psychology, 2017[Aug], Vol
      113[2], 244-253). In the commentary, there was an error in the References list.
      The publishing year for the 18th article was cited incorrectly as 2016. The in
      text acronym associated with this citation should read instead as LCL2017. The
      correct References list citation should read as follows: LeBel, E. P., Campbell,
      L., & Loving, T. J. (2017). Benefits of open and high-powered research outweigh
      costs. Journal of Personality and Social Psychology, 113, 230-243.
      http://dx.doi.org/10 .1037/pspi0000049. The online version of this article has
      been corrected. (The following abstract of the original article appeared in
      record 2017-30567-002.) Finkel, Eastwick, and Reis (2015; FER2015) argued that
      psychological science is better served by responding to apprehensions about
      replicability rates with contextualized solutions than with one-size-fits-all
      solutions. Here, we extend FER2015's analysis to suggest that much of the
      discussion of best research practices since 2011 has focused on a single feature
      of high-quality science-replicability-with insufficient sensitivity to the
      implications of recommended practices for other features, like discovery,
      internal validity, external validity, construct validity, consequentiality, and
      cumulativeness. Thus, although recommendations for bolstering replicability have
      been innovative, compelling, and abundant, it is difficult to evaluate their
      impact on our science as a whole, especially because many research practices that
      are beneficial for some features of scientific quality are harmful for others.
      For example, FER2015 argued that bigger samples are generally better, but also
      noted that very large samples ("those larger than required for effect sizes to
      stabilize"; p. 291) could have the downside of commandeering resources that would
      have been better invested in other studies. In their critique of FER2015, LeBel,
      Campbell, and Loving (2016) concluded, based on simulated data, that ever-larger
      samples are better for the efficiency of scientific discovery (i.e., that there
      are no tradeoffs). As demonstrated here, however, this conclusion holds only when
      the replicator's resources are considered in isolation. If we widen the
      assumptions to include the original researcher's resources as well, which is
      necessary if the goal is to consider resource investment for the field as a
      whole, the conclusion changes radically-and strongly supports a tradeoff-based
      analysis. In general, as psychologists seek to strengthen our science, we must
      complement our much-needed work on increasing replicability with careful
      attention to the other features of a high-quality science. (PsycINFO Database
      Record

PMID- 29016167
TI  - Beyond happiness: Building a science of discrete positive emotions.
AB  - While trait positive emotionality and state positive-valence affect have long
      been the subject of intense study, the importance of differentiating among
      several "discrete" positive emotions has only recently begun to receive serious
      attention. In this article, we synthesize existing literature on positive emotion
      differentiation, proposing that the positive emotions are best described as
      branches of a "family tree" emerging from a common ancestor mediating adaptive
      management of fitness-critical resources (e.g., food). Examples are presented of
      research indicating the importance of differentiating several positive emotion
      constructs. We then offer a new theoretical framework, built upon a foundation of
      phylogenetic, neuroscience, and behavioral evidence, that accounts for core
      features as well as mechanisms for differentiation. We propose several directions
      for future research suggested by this framework and develop implications for the
      application of positive emotion research to translational issues in clinical
      psychology and the science of behavior change. (PsycINFO Database Record

PMID- 29016168
TI  - Voice-only communication enhances empathic accuracy.
AB  - This research tests the prediction that voice-only communication increases
      empathic accuracy over communication across senses. We theorized that people
      often intentionally communicate their feelings and internal states through the
      voice, and as such, voice-only communication allows perceivers to focus their
      attention on the channel of communication most active and accurate in conveying
      emotions to others. We used 5 experiments to test this hypothesis (N = 1,772),
      finding that voice-only communication elicits higher rates of empathic accuracy
      relative to vision-only and multisense communication both while engaging in
      interactions and perceiving emotions in recorded interactions of strangers.
      Experiments 4 and 5 reveal that voice-only communication is particularly likely
      to enhance empathic accuracy through increasing focused attention on the
      linguistic and paralinguistic vocal cues that accompany speech. Overall, the
      studies question the primary role of the face in communication of emotion, and
      offer new insights for improving emotion recognition accuracy in social
      interactions. (PsycINFO Database Record

PMID- 29016170
TI  - Online social network data as sociometric markers.
AB  - Data from online social networks carry enormous potential for psychological
      research, yet their use and the ethical implications thereof are currently hotly
      debated. The present work aims to outline in detail the unique information
      richness of this data type and, in doing so, to support researchers when deciding
      on ethically appropriate ways of collecting, storing, publishing, and sharing
      data from online sources. Focusing on the very nature of social networks, their
      structural characteristics, and depth of information, we provide a detailed and
      accessible account of the challenges associated with data management and data
      storage. In particular, the general nonanonymity of network data sets is
      discussed, and an approach is developed to quantify the level of uniqueness that
      a particular online network bestows upon the individual maintaining it. Using
      graph enumeration techniques, we show that comparatively sparse information on a
      network is suitable as a sociometric marker that allows for the identification of
      an individual from the global population of online users. The impossibility of
      anonymizing specific types of network data carries implications for ethical
      guidelines and research practice. At the same time, network uniqueness opens up
      opportunities for novel research in psychology. (PsycINFO Database Record

PMID- 29016171
TI  - The psychology of neurofeedback: Clinical intervention even if applied placebo.
AB  - Advocates of neurofeedback make bold claims concerning brain regulation,
      treatment of disorders, and mental health. Decades of research and thousands of
      peer-reviewed publications support neurofeedback using electroencephalography
      (EEG-nf); yet, few experiments isolate the act of receiving feedback from a
      specific brain signal as a necessary precursor to obtain the purported benefits.
      Moreover, while psychosocial parameters including participant motivation and
      expectation, rather than neurobiological substrates, seem to fuel clinical
      improvement across a wide range of disorders, for-profit clinics continue to
      sprout across North America and Europe. Here, we highlight the tenuous evidence
      supporting EEG-nf and sketch out the weaknesses of this approach. We challenge
      classic arguments often articulated by proponents of EEG-nf and underscore how
      psychologists and mental health professionals stand to benefit from studying the
      ubiquitous placebo influences that likely drive these treatment outcomes.
      (PsycINFO Database Record

PMID- 29016172
TI  - Addiction training in clinical psychology: Are we keeping up with the rising
      epidemic?
AB  - Addiction has emerged as a serious public health crisis. Clinical psychology as a
      hub science has a long-standing interest in addiction and is particularly well
      suited to offer multifaceted treatment to those struggling with substance use
      disorders. To examine how well clinical psychology training is addressing this
      proliferation of addiction-related problems, we surveyed the directors of
      clinical training at all APA-accredited U.S. clinical psychology doctoral
      programs on 7 occasions between 1999 and 2013. The number of clinical programs
      rose from 181 to 237 programs across the years, with at least 95% response at
      each wave of data collection. Results indicated that less than 40% of programs
      had even 1 faculty member studying addiction, and less than 1 third offered any
      specialty clinical training in addiction. Results also revealed that both the
      percentage of programs reporting any faculty studying addiction and the
      percentage of programs offering specialty clinics in addiction have not increased
      over the 14-year period. We argue that clinical psychology training must bolster
      its focus on addiction research and practice. (PsycINFO Database Record

PMID- 29016173
TI  - Adaptability-what it is and what it is not: Comment on Chandra and Leong (2016).
AB  - Chandra and Leong (2016) propose a new model of adaptability: the diversified
      portfolio model (DPM) of adaptability. Further thought and research on
      adaptability is a welcome addition to the limited body of work conducted on this
      topic to date. However, in their discussion there is a lack of definitional
      clarity, and there is frequent conflation of adaptability and resilience. It is
      also the case that the hypothesized adaptability model is general and could apply
      to many psychological constructs and processes (not just adaptability). In
      addition, there are gaps in research suggested by the authors that have been
      addressed by other researchers and there is a good deal of contemporary
      adaptability research that is not cited. Addressing these limitations in future
      work is vital to the further development of theory, research, and practice in the
      area of adaptability. (PsycINFO Database Record

PMID- 29016169
TI  - The microbiome as a novel paradigm in studying stress and mental health.
AB  - At the intersection between neuroscience, microbiology, and psychiatry, the
      enteric microbiome has potential to become a novel paradigm for studying the
      psychobiological underpinnings of mental illness. Several studies provide support
      for the view that the enteric microbiome influences behavior through the
      microbiota-gut-brain axis. Moreover, recent findings are suggestive of the
      possibility that dysregulation of the enteric microbiota (i.e., dysbiosis) and
      associated bacterial translocation across the intestinal epithelium may be
      involved in the pathophysiology of stress-related psychiatric disorders,
      particularly depression. The current article reviews preliminary evidence linking
      the enteric microbiota and its metabolites to psychiatric illness, along with
      separate lines of empirical inquiry on the potential involvement of psychosocial
      stressors, proinflammatory cytokines and neuroinflammation, the hypothalamic
      pituitary-adrenal axis, and vagal nerve activation, respectively, in this
      relationship. Finally, and drawing on these independent lines of research, an
      integrative conceptual model is proposed in which stress-induced enteric
      dysbiosis and intestinal permeability confer risk for negative mental health
      outcomes through immunoregulatory, endocrinal, and neural pathways. (PsycINFO
      Database Record

PMID- 29016175
TI  - Missing developmental and sociocultural perspectives: Comment on the "Psychology
      of Terrorism" special issue (2017).
AB  - Two critical perspectives were missing from the special issue entitled
      "Psychology of Terrorism": developmental and sociocultural. From a developmental
      point of view, the fact that most individuals who engage in terrorist groups or
      terroristic acts are young men is critically important. Perspectives from
      adolescent development, neuroscience, and social psychology can shed light on why
      this is the case. In addition, sociocultural perspectives are needed to answer
      important community-level questions, such as why some communities are more prone
      to having youth recruited for terrorism than others. From these perspectives, it
      is possible to see clearly how discrimination, social oppression, and
      victimization lead to negative developmental outcomes such as terrorist acts.
      Lastly, understanding individual and community level resilience against terrorism
      is necessary. (PsycINFO Database Record

PMID- 29016174
TI  - Diverse perspectives are welcome: Reply to Martin (2017).
AB  - Martin's (2017) comment on Chandra and Leong (2016) highlighted (a) lack of
      definitional clarity of the concept of adaptability, (b) conceptual generality of
      the model, and (c) incomplete citations of the literature on adaptability. In
      this reply, the authors contend that lack of definitional clarity of adaptability
      is symptomatic of the multitude of definitions of adaptability by psychologists
      of diverse persuasions. Conceptual generality of the diversified portfolio model
      (DPM) stems from the choice of a broad definition of adaptability, which extends
      beyond the narrower definitions provided by scholars including Martin, as well as
      the capability of the model to mesh with this broad definition. Incomplete
      citations result from the choice to use a few well-known conceptualizations of
      adaptability for the purpose of exposition from among the thousands of extant
      studies on adaptability. The central point of Chandra and Leong (2016) is that
      diversification is an important antecedent and determinant of adaptability and
      imparts greater adaptability however defined or measured. (PsycINFO Database
      Record

PMID- 29016176
TI  - Witch persecutions and torture: Comment on Alison and Alison (2017).
AB  - In their article Alison and Alison (2017) argue that historical experiences speak
      against the efficacy of torture. In this comment experiences from the witch
      persecutions in Europe during the 15th to 17th centuries that support this notion
      are discussed. Converging data suggests that torture was often instrumental in
      making large numbers of suspects confess to flying children through the air to
      nocturnal satanic meetings, during this period. A comparison of the number of
      false self incriminating confessions given during the Swedish witch trial in the
      parish of Rattvik 1671 (before royal sanction of torture was given) and the
      parish of Ockelbo 1675 (after royal sanction of torture was given) is used to
      illustrate this point. (PsycINFO Database Record

PMID- 29016177
TI  - Toward a globally informed psychology of humiliation: Comment on McCauley (2017).
AB  - There has never been a more urgent time for psychologists to gain a broader and
      deeper understanding of the pernicious dynamics of humiliation. Congratulations
      to the American Psychologist for introducing an article on the topic of
      humiliation and asymmetric conflict. Based on more than 20 years of research, a
      global community of scholars has established humiliation studies as a field of
      academic inquiry and has built a solid foundation of expertise on the phenomenon
      of humiliation and its impact. Open violence is only the tip of the iceberg. This
      commentary offers substantial clarifications and updates in support of McCauley's
      article and invites psychologists to recognize their vital role in developing
      research and clinical practice to address the explosive consequences of
      humiliation around the globe. (PsycINFO Database Record

PMID- 29016178
TI  - Jerome S. Bruner (1915-2016).
AB  - Presents an obituary for Jerome S. Bruner, who died in 2016. His long, and
      productive, life spanned much of the first century of experimental psychology and
      coincided with the launching of cognitive psychology, a field in which he played
      an indispensable and pioneering role. His innovative and provocative work
      constantly challenged the current "mainstream." His impact on education has been
      equated with that of John Dewey. He was driven throughout his life to pursue the
      nature of the "human" in both his conceptual and empirical work. The model of an
      active organizing mind, "going beyond the information given," informed Jerry's
      work on cognition and led to the influential 1956 book A Study of Thinking, with
      Jacqueline Goodnow and George Austin. In 1960, Bruner and George Miller
      established the Center for Cognitive Studies at Harvard, which became a crucible
      for dynamic innovation across several disciplines and research approaches
      (PsycINFO Database Record

PMID- 29016179
TI  - George Mandler (1924-2016).
AB  - Presents an obituary for George Mandler, who died in London on May 6, 2016 at the
      age of 91. Mandler was one of the pioneers of the cognitive revolution in
      psychology. He was instrumental in moving the study of human learning from
      notions based largely on associations to a view of memory as an organized, nested
      hierarchical structure. Mandler was also a major proponent of the dual-process
      theory of recognition memory, in which general feelings of familiarity are
      distinguished from the context-rich experience of recollection. He brought the
      study of emotion into prominence, suggesting how emotion and cognition are
      related. Finally, he repatriated the concept of consciousness from its
      intellectual exile under behaviorism, stating boldly in 1975 that the construct
      was respectable, useful, and probably necessary. Mandler edited the Psychological
      Review from 1970 to 1976, chaired the Governing Board of the Psychonomic Society,
      and was president of APA Divisions 1 (General Psychology) and 3 (Experimental
      Psychology and Cognitive Science). (PsycINFO Database Record

PMID- 29016180
TI  - Albert Pepitone (1925-2016).
AB  - Presents an obituary for Albert Pepitone, who died on March 17, 2016, in
      Philadelphia at the age of 91. Pepitone was a renowned social psychologist and
      professor emeritus at the University of Pennsylvania. His expertise in social
      psychology opened up areas that significantly broadened its scope, in particular
      calling attention to cultural issues. wrote extensively, including many scholarly
      articles and contributions to published volumes. Pepitone's research was largely
      experimental, testing hypotheses in cognitive, motivational, interpersonal, and
      group processes. He was active in several psychological organizations and was a
      fellow of both the American Psychological Association and the Society of
      Experimental Psychology. (PsycINFO Database Record

PMID- 29016181
TI  - Gerald Roy Patterson (1926-2016).
AB  - Presents an obituary for Gerald ("Jerry") Roy Patterson, who passed away on
      August 22, 2016. Jerry was an intellectual powerhouse who made fundamental
      contributions to developmental psychology, clinical psychology, school
      psychology, prevention science, and special education. In 1965 Jerry became the
      director of clinical training at the University of Oregon and professor of
      clinical psychology. In 1967 he joined the Oregon Research Institute, where he
      continued to study aggression, marital conflict, and treatment. Ten years later,
      he founded the Oregon Social Learning Center (OSLC), where he remained for the
      duration of his career. Jerry received numerous awards for his scientific
      activity, including a National Institute of Mental Health Merit Award, the Urie
      Bronfenbrenner Award, the Presidential Award from the Society of Prevention
      Research, a Distinguished Scientist Award from the American Psychological
      Association (APA), the G. Stanley Hall Award from APA Division 7 (Developmental
      Psychology), and a Distinguished Scientist Award from the Society for Research in
      Child Development. (PsycINFO Database Record

PMID- 29016182
TI  - Martin M. Katz (1927-2017).
AB  - Presents an obituary for Martin M. Katz, who passed away on January 12, 2017 in
      Rockville, Maryland. Katz was the director of clinical research at the National
      Institute of Mental Health (NIMH; 1968-1978). Following Katz's retirement from
      his administration and scientific career at NIMH, he served as professor and
      director of clinical psychology training at Albert Einstein College of Medicine
      Medical College in New York (1984-1994). Until his final days, Katz served as a
      participating and consulting scientist in the longitudinal collaborative research
      projects he and colleagues initiated to investigate psychopharmacological
      treatments for depression. (PsycINFO Database Record

PMID- 29016183
TI  - Paul W. Thayer (1927-2017).
AB  - Presents an obituary for Paul W. Thayer, who died on January 25, 2017, at the age
      of 89. Thayer was an industrial and organizational psychologist probably most
      distinguished by his professional service. He was a fellow of the American
      Psychological Association (APA), American Psychological Society (APS), and
      Society for Industrial and Organizational Psychology (SIOP). He received multiple
      awards for his service, including SIOP's Distinguished Professional Contributions
      Award (1986) and its Distinguished Service Award (1990), as well as the APA Award
      for Distinguished Service to Psychological Science (2014). Paul's most recognized
      scientific contribution was in industrial training. He coauthored (with William
      McGehee) the first scientific book on the topic titled, Training in Business and
      Industry (New York, NY: Wiley), in 1961, which is considered a classic in the
      field. (PsycINFO Database Record

PMID- 29016184
TI  - The structure of group task performance-A second look at "collective
      intelligence": Comment on Woolley et al. (2010).
AB  - Collective intelligence has been described as a general factor that "explains a
      group's performance on a wide variety of tasks" (Woolley, Chabris, Pentland,
      Hashmi, & Malone, 2010, p. 686), much like the general intelligence factor
      explains individuals' performance on cognitive ability tasks. This construct has
      received widespread attention in both the media and academic community. In this
      article we reexamine the data from 6 previously published samples that have been
      used to examine the existence of the collective intelligence construct and show
      that the empirical support for the construct is generally weak. Specifically, we
      show that the general factor explains only little variance in the performance on
      many group tasks. We also highlight how 2 statistical artifacts-the apparent
      presence of low effort responding and the nested nature of the data-may also have
      inflated the little covariation that exists between group performance on
      different tasks. These findings suggest that there is insufficient support for
      the existence of a collective intelligence construct. (PsycINFO Database Record

PMID- 29016185
TI  - Clinical Outcomes of Knee Osteoarthritis Treated With an Autologous Protein
      Solution Injection: A 1-Year Pilot Double-Blinded Randomized Controlled Trial.
AB  - BACKGROUND: Osteoarthritis (OA) is a debilitating disease resulting in
      substantial pain and functional limitations. A novel blood derivative has been
      developed to concentrate both growth factors and antagonists of inflammatory
      cytokines, with promising preliminary findings in terms of safety profile and
      clinical improvement. PURPOSE: To investigate if one intra-articular injection of
      autologous protein solution (APS) can reduce pain and improve function in
      patients affected by knee OA in a multicenter, randomized, double-blind, saline
      controlled study. STUDY DESIGN: Randomized controlled trial; Level of evidence,
      2. METHODS: Forty-six patients with unilateral knee OA (Kellgren-Lawrence 2 or 3)
      were randomized into the APS group (n = 31), which received a single ultrasound
      guided injection of APS, and the saline (control) group (n = 15), which received
      a single saline injection. Patient-reported outcomes and adverse events were
      collected at 2 weeks and at 1, 3, 6, and 12 months through visual analog scale
      (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC),
      Knee injury and Osteoarthritis Outcome Score (KOOS), Short Form-36 (SF-36),
      Clinical Global Impression of Severity/Change (CGI-S/C), Patient Global
      Impression of Severity/Change (PGI-S/C), and Outcome Measures in Rheumatology
      Osteoarthritis Research Society International (OMERACT-OARSI) responder rate.
      Imaging evaluation was also performed with radiograph and magnetic resonance
      imaging (MRI) before and after treatment (12 months and 3 and 12 months,
      respectively). RESULTS: The safety profile was positive, with no significant
      differences in frequency and severity of adverse events between groups. The
      improvement from baseline to 2 weeks and to 1, 3, and 6 months was similar
      between treatments. At 12 months, improvement in WOMAC pain score was 65% in the
      APS group and 41% in the saline group ( P = .02). There were no significant
      differences in VAS pain improvement between groups. At 12 months, APS group
      showed improved SF-36 Bodily Pain subscale ( P = .0085) and Role Emotional Health
      subscale ( P = .0410), as well as CGI-C values ( P = .01) compared with saline
      control. Significant differences between groups were detected in change from
      baseline to 12 months in bone marrow lesion size as assessed on MRI and
      osteophytes in the central zone of the lateral femoral condyle, both in favor of
      the APS group ( P = .041 and P = .032, respectively). There were no significant
      differences between APS and control groups in other measured secondary endpoints.
      CONCLUSION: This study provides evidence to support the safety and clinical
      improvement at 1-year follow-up of a single intra-articular injection of APS in
      patients affected by knee OA. Treatment with APS or a saline injection provided
      significant pain relief over the course of the study with differences becoming
      apparent at between 6 and 12 months after treatment. TRIAL REGISTRATION:
      NCT02138890 ( ClinicalTrials.gov identifier).

PMID- 29016186
TI  - Adherence of Ornithobacterium rhinotracheale to chicken embryo lung cells as a
      pathogenic mechanism.
AB  - Ornithobacterium rhinotracheale is a bacterium that causes respiratory disease in
      birds and it has been isolated in countries with a large poultry production,
      including Mexico. The pathogenicity mechanisms of this bacterium have not been
      completely elucidated yet. The capacity of the bacterium to adhere to epithelial
      cells of chicken in vitro has been evidenced, and since this bacterium has been
      isolated from the lungs and air sacs of several avian species, the aim of this
      study was to determine if this bacterium can adhere to chicken lung cells. We
      used five O. rhinotracheale reference serovars (A-E) that were in contact with
      primary lung cells cultured from a 19-day-old chicken embryo. O. rhinotracheale
      adherence was evaluated through optical and transmission electron microscopies.
      The results revealed that O. rhinotracheale is capable of adhering to chicken
      embryo lung cells within 3 h of incubation with a diffuse adherence pattern. The
      adherence percentages of the chicken embryo lung cells were 51-96% according to
      the serovar of the bacterium. Relative adherence was from 4 to 8 bacteria per
      cell. Transmission electron microscope data revealed intracellular bacteria
      inside a vacuole in less than 3 h of incubation.

PMID- 29016188
TI  - Design of Two Multiplex PCR Assays for Serotyping Shigella flexneri.
AB  - Shigella flexneri is a major health problem in developing countries. There are 19
      serotypes recognized based on O-antigen structure and its typing is important for
      epidemiological purposes. However, the diversity of serotypes and the
      difficulties presented by phenotypic serotyping, for example, unavailable
      antisera for less common antigens, require the implementation of molecular
      techniques. In this study, we developed two multiplex PCR assays targeting the O
      antigen synthesis genes and the O-antigen modification genes, for the rapid
      identification of S. flexneri serotypes 1/7, 2, 4, 5, and 6 (PCR A) and serotype
      7 and group antigenic factors (3,4; 6; 7,8; E1037) (PCR B). A total of 73 S.
      flexneri strains representing 18 serotypes, except serotype 1d, were used in the
      study. Specific amplification patterns were obtained for each of the different
      serotypes. All strains tested had concordant results with phenotypic and
      genotypic serotyping; therefore, its implementation in the microbiology clinical
      laboratory will significantly improve S. flexneri serotyping.

PMID- 29016187
TI  - Quantitative and Qualitative Analysis of the Medial Patellar Ligaments: An
      Anatomic and Radiographic Study.
AB  - BACKGROUND: The qualitative and quantitative anatomy of the medial patellar
      stabilizers has been reported; however, a quantitative analysis of the anatomic
      and radiographic attachments of all 4 ligaments relative to anatomic and osseous
      landmarks, as well as to one another, has yet to be performed. PURPOSE: To
      perform a qualitative and quantitative anatomic and radiographic evaluation of
      the medial patellofemoral ligament (MPFL), medial patellotibial ligament (MPTL),
      medial patellomeniscal ligament (MPML), and medial quadriceps tendon femoral
      ligament (MQTFL) attachment sites, with attention to their relationship to
      pertinent osseous and soft tissue landmarks. STUDY DESIGN: Descriptive laboratory
      study. METHODS: Ten nonpaired fresh-frozen human cadaveric knees were dissected,
      and the MPFL, MPTL, MPML, and MQTFL were identified. A coordinate measuring
      device quantified the attachment areas of each structure and its relationship to
      pertinent bony landmarks. Radiographic analysis was performed through ligament
      attachment sites and relevant anatomic structures to assess their locations
      relative to pertinent bony landmarks. RESULTS: Four separate medial patellar
      ligaments were identified in all specimens. The center of the MPFL attachments
      was 14.3 mm proximal and 2.1 mm posterior to the medial epicondyle and 8.3 mm
      distal and 2.7 mm anterior to the adductor tubercle on the femur and 8.9 mm
      distal and 19.9 mm medial to the superior pole on the patella. The MQTFL had a
      mean insertion length of 29.3 mm on the medial aspect of the distal quadriceps
      tendon. The MPTL and MPML shared a common patellar insertion and were 9.1 mm
      proximal and 15.4 mm medial to the inferior pole. The MPTL attachment inserted on
      a newly identified bony ridge, which was located 5.0 mm distal to the joint line.
      The orientation angles of the MPTL and MPML with respect to the patellar tendon
      were 8.3 degrees  and 22.7 degrees , respectively. CONCLUSION: The most important
      findings of this study were the correlative anatomy of 4 distinct medial patellar
      ligaments (MPFL, MPTL, MPML, MQTFL), as well as the identification of a bony
      ridge on the medial proximal tibia that consistently served as the attachment
      site for the MPTL. The quantitative and radiographic measurements, while
      comparable with current literature, detailed the meniscal insertion of the MPML
      and defined a patellar insertion of the MPTL and the MPML as a single attachment.
      The data allow for reproducible landmarks to be established from previously known
      bony and soft tissue structures. CLINICAL RELEVANCE: The findings of this study
      provide the anatomic foundation needed for an improved understanding of the role
      of medial-sided patellar restraints. This will help to further refine injury
      patterns and/or soft tissue deficiencies that result in lateral patellar
      instability, which can then be addressed with an anatomic-based reconstruction or
      repair technique and potentially lead to improved outcomes.

PMID- 29016189
TI  - Early and 24 h post-mortem thigh (ilio tibialis) muscle metabolism and meat
      quality in two genetic types of turkeys and their reciprocal crosses, raised
      under semi-confined conditions.
AB  - 1. The experiment was conducted in order to determine the effect of the direction
      of turkey crossing on quality traits of their thigh muscle. 2. In total, 1358
      turkeys of slow- (SG) and fast-growing (FG) lines as well as SF crosses (SG * FG)
      and FS crosses (FG * SG) were reared with access to free range to 21 weeks of age
      in the case of males and 15 weeks of age in the case of hens. 3. After slaughter
      of 15 males and 15 hens from each genetic line, their thigh muscles were examined
      and the following traits were measured after 5-min, 45-min, 2-h and 24-h post
      mortem: temperature, pH, glycogen content (G), lactate content (L) and electrical
      conductivity (EC). Quality attributes were evaluated based on chemical
      composition, water holding capacity, cooking loss (%) and colour. 4. The rate of
      post-mortem changes in temperature, G, L and pH in muscles differed among the 4
      lines of turkeys, with the highest metabolic rate determined for muscles of SG
      turkeys, followed by muscles of SF, FS and FG birds. A more beneficial muscle
      water holding capacity of both sexes of turkeys and better results of cooking
      loss in male muscles were found in SG and SF turkeys. The thigh muscles of the
      crosses were characterised by a higher content of protein and a lower content of
      fat compared to the muscles of FG turkeys, and in the case of the males also by a
      higher protein content compared to the muscles of SG birds. 5. Owing to the
      faster post-mortem metabolism, better water holding capacity, lower cooking loss
      and fat content at a similar content of protein, the thigh muscles of SF crosses
      raised in the free range system represent a better quality of meat for consumers
      compared to the thigh muscles of FS turkeys.

PMID- 29016190
TI  - Effect of flapless osteoperforation-assisted tooth movement on atrophic alveolar
      ridge: Histomorphometric and gene-enrichment analysis.
AB  - OBJECTIVE: To investigate the effect of flapless osteoperforation on the tissue
      response of the atrophic alveolar ridge affected by orthodontic tooth movement
      (OTM). MATERIALS AND METHODS: An atrophic alveolar ridge model was established in
      the mandibular quadrants of eight beagle dogs. As a split-mouth design, the
      quadrants were randomly divided into group C (OTM only) and group OP (OTM with
      flapless osteoperforation). The rate of OTM for 10 weeks was compared between
      groups, and micro-CT-based histomorphometric analysis and RNA-sequencing-based
      gene-enrichment analysis were performed targeting the atrophic ridge. RESULTS:
      Group OP displayed more rapid tooth movement with lower bone mineral density and
      higher trabecular fraction in the atrophic ridge than did group C, showing no
      intergroup difference of total ridge volume. As contributing biological
      functional pathways in group OP, the genes related to osteoclast differentiation
      and TNF signaling pathway were up-regulated and those associated with Wnt
      signaling pathway and AMPK signaling pathway were down-regulated. CONCLUSIONS:
      Flapless osteoperforation facilitated the rate of OTM toward the atrophic ridge,
      maintaining low bone density, whereas it did not increase the volume of the
      atrophic ridge.

PMID- 29016191
TI  - Treatment changes of hypo- and hyperdivergent Class II Herbst patients.
AB  - OBJECTIVES: To determine the relative effects of Herbst appliance therapy in hypo
      and hyperdivergent patients. MATERIALS AND METHODS: The treated group included
      45 growing Class II, division 1, patients treated with stainless steel crown
      Herbst appliances, followed by fixed edgewise appliances. The untreated control
      group consisted of 45 Class II, division 1, subjects, matched to the treated
      sample based on Angle classification, age, sex, and pretreatment mandibular plane
      angle (MPA). Subjects were categorized as hypo- or hyperdivergent based on their
      MPAs. Pre- and posttreatment cephalograms were traced and superimposed on cranial
      base and mandibular structures. RESULTS: The primary effect of the Herbst in
      terms of maxillomandibular correction was in the maxilla. It significantly
      restricted maxillary growth, producing a "headgear effect." Mandibular treatment
      changes depended on divergence. Hyperdivergent patients experienced a deleterious
      backward true mandibular rotation with Herbst treatment. Hypodivergent patients,
      as well as untreated hypo- and hyperdivergent controls, underwent forward true
      mandibular rotation. However, hypodivergent chins did not advance any more than
      expected for untreated hypodivergent Class II patients. CONCLUSIONS: Hypo- and
      hyperdivergent patients benefit from the Herbst's headgear effect. While the
      mandibular growth of hypodivergent patients overcomes the negative rotational
      effects, hyperdivergent patients undergo a deleterious backward mandibular
      rotation and increases in facial height.

PMID- 29016192
TI  - Added Value of Preoperative Computed Tomography for Determining Cartilage
      Degeneration in Patients With Osteochondral Lesions of the Talar Dome.
AB  - BACKGROUND: Osteochondral lesions of the talar dome (OLTs) involve the articular
      cartilage and subchondral bone. The subchondral bone plate (SBP) plays a crucial
      role in cartilage metabolism, and computed tomography (CT) can provide more
      precise information on subchondral bone. CT image prediction of the histological
      findings on OLT will be useful to determine the most appropriate therapeutic
      strategy. PURPOSE: To evaluate the unique features of the CT findings that relate
      to the condition of the articular cartilage in OLT. STUDY DESIGN: Cohort study;
      Level of evidence, 3. METHODS: Thirty ankles in 29 patients who had OLT with an
      osteochondral fragment were retrospectively reviewed. At surgery, the
      osteochondral fragment of 19 ankles could be preserved (preservation group) by
      fixation or drilling, and in the remaining 11 ankles, the osteochondral fragment
      was removed (excision group). Preoperative CT findings were compared between the
      2 groups. Biopsies of the osteochondral fragment from 13 ankles were performed.
      The relationship between the CT and histological findings were evaluated.
      RESULTS: The area of lesion in the preservation group was significantly larger
      than that in the excision group. The CT images of the lesion showed the rate of
      absorption of the SBP in the preservation group to be lower than that in the
      excision group. As for the lesion bed absorption, it was higher in the
      preservation group than in the excision group. All cases in the excision group
      showed bed sclerosis, compared with 42.1% in the preservation group. The
      specimens with disruption of the SBP exhibited cartilage degeneration and
      abundant chondrocyte cloning. OLT with absorption of the SBP on CT showed severe
      cartilage degeneration, while the remaining SBP on CT showed low-grade cartilage
      degeneration. CONCLUSION: This study shows the features of preoperative CT and
      histological findings in OLT with osteochondral fragments. The condition of the
      SBP affects the cartilage degeneration. CT findings provide important information
      for the determination of surgical treatment.

PMID- 29016194
TI  - Outcomes After Operative and Nonoperative Treatment of Proximal Hamstring
      Avulsions: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: No meta-analysis has compared outcomes of operative and nonoperative
      proximal hamstring avulsion treatment. PURPOSE: To compare outcomes of operative
      and nonoperative proximal hamstring avulsion treatment, including acute, chronic,
      partial, and complete repairs. STUDY DESIGN: Meta-analysis. METHODS: PubMed,
      CINAHL, SPORTdiscus, Cochrane Library, EMBASE, and Web of Science were searched
      up to July 2016. Three authors screened the studies and performed quality
      assessment using criteria from the Methodologic Index for Nonrandomized Studies.
      A best evidence synthesis was subsequently used. RESULTS: Twenty-four studies
      (795 proximal hamstring avulsions) were included. Twenty-two studies included
      proximal hamstring avulsion repairs; 1 study had proximal hamstring avulsion
      repairs and a control group of nonoperatively treated proximal hamstring
      avulsions; and 1 study had solely nonoperatively treated proximal hamstring
      avulsions. The majority of studies were of low methodological quality. Overall,
      repairs had significantly higher patient satisfaction (90.81% vs 52.94%),
      hamstring strength (85.01% vs 63.95%), Lower Extremity Functional Scale scores
      (72.77 vs 69.53), and single-legged hop test results (119.1 vs 56.62 cm) (all P <
      .001); complications occurred in 23.17% of cases. Compared with chronic repairs,
      acute avulsion repairs had greater patient satisfaction (95.48% vs 83.79%), less
      pain (1.07 vs 3.71), and greater strength (85.2% vs 82.8%), as well as better
      scores for the Lower Extremity Functional Scale (75.64 vs 71.5), UCLA activity
      scale (University of California, Los Angeles; 8.57 vs 8.10), and Single
      Assessment Numeric Evaluation (93.36 vs 86.50) (all P < .001). Compared with
      partial avulsion repairs, complete avulsion repairs had higher patient
      satisfaction (89.64% vs 81.35%, P < .001), less pain (1.87 vs 4.60, P < .001),
      and higher return to sport or preinjury activity level, but this was
      insignificant (81.43% vs 73.83%, P = .082). Partial avulsion repairs had better
      hamstring strength (86.04% vs 83.71%, P < .001) and endurance (107.13% vs
      100.17%, P < .001). Complete repairs had significantly higher complication rates
      (29.38% vs 11.27%, P = .001). CONCLUSION: Proximal hamstring avulsion repair
      resulted in superior outcomes as compared with nonoperative treatment, although
      the complication rate was 23.17%. The nonoperative group was quite small, making
      a true comparison difficult. Acute repairs have better outcomes than do chronic
      repairs. Complete avulsion repairs had higher patient satisfaction, less pain,
      and a higher complication rate than partial avulsion repairs, although partial
      avulsion repairs had better hamstring strength and endurance. Studies of high
      methodological quality are lacking in terms of investigating the outcomes of
      proximal hamstring avulsion repairs.

PMID- 29016197
TI  - Nutritional Therapy for Patients with Esophageal Cancer.
AB  - Malnutrition develops in 79% patients with esophageal cancer. Thus, these
      patients represent a group of cancer patients, which is the most nutritionally
      compromised. Dysphagia and more than 10% loss of body weight are already present
      at the time of diagnosis. Treatments for esophageal cancer contribute
      significantly to the development of malnutrition. This paper describes the
      nutritional treatment of patients and nutritional strategies in patients with
      dysphagia and other nutritional problems that accompany the treatment of patients
      with esophageal cancer. Here are shown the types and methods of nutritional
      support, which are suitable for this group of patients. Nutritional support of
      patients with esophageal cancer is performed as a parallel therapeutic route.

PMID- 29016195
TI  - Critical Assessment of Analytical Techniques in the Search for Biomarkers on
      Mars: A Mummified Microbial Mat from Antarctica as a Best-Case Scenario.
AB  - The search for biomarkers of present or past life is one of the major challenges
      for in situ planetary exploration. Multiple constraints limit the performance and
      sensitivity of remote in situ instrumentation. In addition, the structure,
      chemical, and mineralogical composition of the sample may complicate the analysis
      and interpretation of the results. The aim of this work is to highlight the main
      constraints, performance, and complementarity of several techniques that have
      already been implemented or are planned to be implemented on Mars for detection
      of organic and molecular biomarkers on a best-case sample scenario. We analyzed a
      1000-year-old desiccated and mummified microbial mat from Antarctica by Raman and
      IR (infrared) spectroscopies (near- and mid-IR), thermogravimetry (TG),
      differential thermal analysis, mass spectrometry (MS), and immunological
      detection with a life detector chip. In spite of the high organic content (ca.
      20% wt/wt) of the sample, the Raman spectra only showed the characteristic
      spectral peaks of the remaining beta-carotene biomarker and faint peaks of
      phyllosilicates over a strong fluorescence background. IR spectra complemented
      the mineralogical information from Raman spectra and showed the main molecular
      vibrations of the humic acid functional groups. The TG-MS system showed the
      release of several volatile compounds attributed to biopolymers. An antibody
      microarray for detecting cyanobacteria (CYANOCHIP) detected biomarkers from
      Chroococcales, Nostocales, and Oscillatoriales orders. The results highlight
      limitations of each technique and suggest the necessity of complementary
      approaches in the search for biomarkers because some analytical techniques might
      be impaired by sample composition, presentation, or processing. Key Words:
      Planetary exploration-Life detection-Microbial mat-Life detector chip
      Thermogravimetry-Raman spectroscopy-NIR-DRIFTS. Astrobiology 17, 984-996.

PMID- 29016193
TI  - The Possible Emergence of Life and Differentiation of a Shallow Biosphere on
      Irradiated Icy Worlds: The Example of Europa.
AB  - Irradiated ice-covered ocean worlds with rocky mafic mantles may provide the
      conditions needed to drive the emergence and maintenance of life. Alkaline
      hydrothermal springs-relieving the geophysical, thermal, and chemical
      disequilibria between oceans and tidally stressed crusts-could generate inorganic
      barriers to the otherwise uncontrolled and kinetically disfavored oxidation of
      hydrothermal hydrogen and methane. Ionic gradients imposed across these inorganic
      barriers, comprising iron oxyhydroxides and sulfides, could drive the
      hydrogenation of carbon dioxide and the oxidation of methane through
      thermodynamically favorable metabolic pathways leading to early life-forms. In
      such chemostatic environments, fuels may eventually outweigh oxidants. Ice
      covered oceans are primarily heated from below, creating convection that could
      transport putative microbial cells and cellular cooperatives upward to congregate
      beneath an ice shell, potentially giving rise to a highly focused shallow
      biosphere. It is here where electron acceptors, ultimately derived from the
      irradiated surface, could be delivered to such life-forms through exchange with
      the icy surface. Such zones would act as "electron disposal units" for the
      biosphere, and occupants might be transferred toward the surface by buoyant
      diapirs and even entrained into plumes. Key Words: Biofilms-Europa
      Extraterrestrial life-Hydrothermal systems. Astrobiology 17, 1265-1273.

PMID- 29016196
TI  - Prevalence of GJB2 Mutations in Affected Individuals from United Arab Emirates
      with Autosomal Recessive Nonsyndromic Hearing Loss.
AB  - AIM: Mutations in the gap junction protein beta 2 (GJB2) gene are responsible for
      more cases of nonsyndromic recessive hearing loss than any other gene. The
      purpose of our study was to evaluate the prevalence of GJB2 mutations among
      affected individuals from United Arab Emirates (UAE). METHODS: There were 50
      individuals diagnosed with hereditary hearing loss and 120 healthy individuals
      enrolled in the study. The Sanger sequencing method was used to screen the GJB2
      coding region in all affected individuals. The c.-1G>A variant was determined by
      the polymerase chain reaction-restriction fragment length polymorphism method in
      normal individuals. RESULTS AND DISCUSSION: Nine cases with bi-allelic mutations
      and three cases with mono-allelic mutations were detected in 12 out of 50
      patients (24%). The homozygous mutation c.35delG was identified as the cause of
      hearing loss in six participants (12%). The mutation c.506G>A was identified in
      three affected individuals (6%). The allelic frequency (14%) and low percentage
      of individuals that were homozygous (2%) for the c.35delG mutation suggest that
      there are other genes responsible for nonsyndromic deafness in the UAE
      population. The results reported here are a preliminary step in collecting
      epidemiological data regarding autosomal recessive nonsyndromic hearing loss
      related to GJB2 gene mutations among the UAE population. CONCLUSION: The c.35delG
      mutation of the GJB2 gene is the most frequently seen causative mutation in the
      UAE and is followed by the p.Cys169Tyr mutation.

PMID- 29016198
TI  - Carcinogenicity of High Consumption of Meat and Lung Cancer Risk Among Non
      Smokers: A Comprehensive Meta-Analysis.
AB  - Increasing evidence suggests that high consumption of meat is linked to lung
      cancer but the previous meta-analyses did not properly address the role of
      tobacco smoking as a potential confounder. We conducted a meta-analysis to
      investigate the association of lung cancer, among never smokers, with consumption
      of various type of meat, fish, heterocyclic amines and polycyclic aromatic
      hydrocarbons. We performed a systematic literature search and meta-analysis, for
      highest versus lowest consumption and dose-response. The results from random
      effects models summarized data from 14 independent observational studies and 5368
      lung cancer cases. We found a statistically significant 24% increased risk of
      lung cancer for high consumption of red meat (Summary Relative Risk 1.24, 95% CI
      1.01-1.51), based on 11 estimates, with low heterogeneity (I2 = 31%) and no
      indication of publication bias. No significant associations between high
      consumption of other types of meat, fish nor for heterocyclic amines and lung
      cancer risk were detected. No significant risk estimates were found for the
      increase of one serving per week of any type of meat or fish. Our meta-analysis
      suggests that a high intake of red meat may increases the risk of lung cancer
      among never and non-smokers.

PMID- 29016199
TI  - Ability-Based Balancing Using the Gross Motor Function Measure in Exergaming for
      Youth with Cerebral Palsy.
AB  - OBJECTIVE: To test if the gross motor function measure (GMFM) could be used to
      improve game balancing allowing youth with cerebral palsy (CP) with different
      physical abilities to play a cycling-based exercise videogame together. Our
      secondary objective determined if exergaming with the GMFM Ability-Based
      algorithm was enjoyable. MATERIALS AND METHODS: Eight youth with CP, 8-14 years
      of age, GMFM scores between 25.2% and 87.4% (evenly distributed between Gross
      Motor Function Classification System levels II and III), competed against each
      other in head-to-head races, totaling 28 unique race dyads. Dyads raced three
      times, each with a different method of minimizing the distance between
      participants (three balancing algorithms). This was a prospective repeated
      measures intervention trial with randomized and blinded algorithm assignment. The
      GMFM Ability-Based algorithm was developed using a least squares linear
      regression between the players' GMFM score and cycling cadence. Our primary
      outcome was dyad spread or average distance between players. The GMFM Ability
      based algorithm was compared with a control algorithm (No-Balancing), and an
      idealized algorithm (one-speed-for-all [OSFA]). After each race, participants
      were asked "Was that game fun?" and "Was that game fair?" using a five-point
      Likert scale. RESULTS: Participants pedaled quickly enough to elevate their heart
      rate to an average of 120 +/- 8 beats per minute while playing. Dyad spread was
      lower when using GMFM Ability-Based balancing (4.6 +/- 4.2) compared with No
      Balancing (11.9 +/- 6.8) (P < 0.001). When using OSFA balancing, dyad spread was
      (1.6 +/- 0.9), lower than both GMFM Ability-Based (P = 0.006) and No-Balancing (P
      < 0.001). Cycling cadence positively correlated to GMFM, equal to 0.58 (GMFM)
      +33.29 (R2adj= 0.662, P = 0.004). Participants rated the games a median score 4/5
      for both questions: "was that game fun?" and "was that game fair?." CONCLUSION:
      The GMFM Ability-Based balancing decreased dyad spread while requiring
      participants to pedal quickly, facilitating interaction and physical activity.

PMID- 29016202
TI  - The role of plant foods in traditional Wet'suwet'en nutrition.
AB  - This paper investigates the role of plant foods in traditional diet of a northern
      foraging group, the Wet'suwet' en Indians of northwest British Columbia. Plant
      foods were important in the traditional diet of the Wet'suwet'en people, although
      the bulk of calories, protein, minerals and B vitamins were derived from animal
      foods. Plant foods were consumed throughout most or all of the year. Large
      quantities of plant foods, notably berries and fern rhizomes, were collected and
      stored for winter consumption. Critical contributions from plant foods included
      vitamin C, fibre, and carbohydrate to balance the consumption of protein in meat.
      Plant foods also made significant contributions to other nutrients, including
      iron, calcium and magnesium. The role of plant foods in folate nutrition is still
      unclear. Medicinal teas, green vegetables and rice root bulbs (Fritillaria
      camschatcensis) contributed to vitamin C in late winter and spring.

PMID- 29016200
TI  - Analysis of Movement Acceleration of Down's Syndrome Teenagers Playing Computer
      Games.
AB  - OBJECTIVE: This study aimed to evaluate movement acceleration characteristics in
      adolescents with Down syndrome (DS) and typical development (TD), while playing
      bowling and golf videogames on the Nintendo(r) WiiTM. MATERIALS AND METHODS: The
      sample comprised 21 adolescents diagnosed with DS and 33 with TD of both sexes,
      between 10 and 14 years of age. The arm swing accelerations of the dominant upper
      limb were collected as measures during the bowling and the golf games. The first
      valid measurement, verified by the software readings, recorded at the start of
      each of the games, was used in the analysis. RESULTS: In the bowling game, the
      groups presented significant statistical differences, with the maximum (M) peaks
      of acceleration for the Male Control Group (MCG) (M = 70.37) and Female Control
      Group (FCG) (M = 70.51) when compared with Male Down Syndrome Group (MDSG) (M =
      45.33) and Female Down Syndrome Group (FDSG) (M = 37.24). In the golf game the
      groups also presented significant statistical differences, the only difference
      being that the maximum peaks of acceleration for both male groups were superior
      compared with the female groups, MCG (M = 74.80) and FCG (M = 56.80), as well as
      in MDSG (M = 45.12) and in FDSG (M = 30.52). CONCLUSION: It was possible to use
      accelerometry to evaluate the movement acceleration characteristics of teenagers
      diagnosed with DS during virtual bowling and golf games played on the Nintendo
      Wii console.

PMID- 29016203
TI  - Dietary intake changes associated with post-cyclone food aid in Western Samoa.
AB  - This study examines dietary intake responses to a food aid program in Western
      Samoa, which consisted primarily of rice and flour supplements. Using a semi
      quantitative food frequency questionnaire, intake estimates were made for 147
      Samoans (72 men, 75 women), 5 months before and 8 months after a tropical
      cyclone. Study participants were from urban Apia (n = 34) and three rural, more
      traditional villages (n = 113). For the total sample, consumption of rice and
      pancakes more than doubled, and the contribution of these foods to total
      carbohydrate and kilocalorie intake increased approximately three-fold (p <
      0.0001, for paired t-tests). Significant decreases were noted for the nutrient
      contribution from breadfruit and coconut products. These dietary changes were
      significantly less in the urban sub-sample. These results indicate the food aid
      may have accelerated an existing modernizing trend in the diet of Samoans. The
      nutritional and economic implications are discussed within the context of Western
      Samoa.

PMID- 29016204
TI  - Consumption of dietary fiber in rural Mexico.
AB  - The average per capita intake of dietary fibre and the relative contribution of
      different foods to its intake in the Mexican rural population was studied. Food
      consumption data were obtained from the National Nutrition Surveys of 1979
      (21,248 families in 219 rural Mexican communities), and from a similar survey of
      the same communities in 1989 (20,759 families). Average per capita intake of
      total dietary fibre (TDF) ranged from 19.8 to 34.0 g/d (average 27.2 +/- 3.3) in
      1979 and from 17.5 to 27.1 g/d (average 22.5 +/- 2.2) in 1989. About 13% of TDF
      in both surveys was contributed by soluble dietary fibre. Of the 19 regions of
      the country, 18 exhibited a significant reduction in TDF intake from 1979 to 1989
      (p < 0.001). With the exception of two regions on the northern border, maize was
      the major single source of TDF (from 31 to 74% of TDF). The implication of these
      observations on disease patterns needs to be studied.

PMID- 29016205
TI  - Chemical, nutritional and sensory evaluation of green beans fermented with and
      without starter culture.
AB  - Two varieties of green bean locally known as Binz and Mangtout were fermented
      with and without starter culture. During fermentation pH changes, total reducing
      sugars, total acids, thiamine, riboflavin and protein contents were determined.
      After the pH of the beans had fallen to below 4.0 the beans were pasteurized and
      sensory evaluation was carried out to assess the taste, texture, aroma and
      overall acceptability using a 5 point hedonic scale. The pH of the beans
      fermented with starter culture fell to below 4.0 after 4 days whereas the samples
      fermented without starter culture took 8 days. In both cases a sharp decrease in
      sugars and increase in acids were observed within the first two days of
      fermentation but samples fermented without starter produced significantly less
      acids. Although there was a significant decrease (p < 0.05) of the vitamins and
      protein with fermentation period, there were no significant differences between
      samples fermented with and without starter culture. Overall both varieties
      produced acceptable fermented products but samples fermented without starter
      culture were more acceptable than those fermented with starter culture.

PMID- 29016206
TI  - A comparison of transferred receptor with other iron assessment measures in an
      upper-income post partum Jamaican sample.
AB  - Iron (Fe) deficiency is the most prevalent nutritional deficiency in the world.
      During their reproductive years, women are especially vulnerable. However,
      methods of assessing Fe deficiency in countries where both Fe deficiency and
      infection frequently coexist, are not optimal. Frequently used methods do not
      differentiate between anemia due to Fe deficiency or that due to inflammation.
      This study compared several Fe assessment methods (Plasma ferritin, serum
      transferrin receptor (s-TfR), and erythrocyte protoporphyrin) in a six week, post
      partum, upper income sample. A variety of socio-economic, hematological, and
      dietary information was collected from 73 Jamaican women. S-TfR values were
      compared with the other Fe assessment indices using
      sensitivity/specificity/predictive value analysis. Results indicated that anemia
      (Hb < 12.0 g/dl) was present in 37.5% of the sample and that Fe deficient
      erythropoiesis existed in between 7 and 13% depending upon assessment method. S
      TfR was highly specific, but had a low sensitivity and positive predictive value.
      Use of s-TfR and the high percent of anemia are discussed.

PMID- 29016207
TI  - Food bowl division and social change.
AB  - Effective, local food sharing mechanisms are vital if the nutritional needs of
      small-scale communities are to be met. Changes in the ways in which food
      entitlement are decided by villagers in Keneba, The Gambia are described.
      Membership of the consumption unit (sinkird) is the chief means by which
      individuals gain food security. Consumption units are kin-based, but outsiders
      can negotiate membership. The impact on sinkiro structure of two research
      stations based in the village is analysed. Changes in women's position within the
      wage economic sector are reviewed, and the increased level of female
      responsibility for sinkiro provision analysed. Strategies of crisis management
      are linked to economic change and shifting gender relations. The sinkiro endures
      in a rapidly changing environment in which the long-term food security of many
      African communities is threatened.

PMID- 29016209
TI  - Erratum.

PMID- 29016208
TI  - Isotope Discriminations Upon Biosynthesis in Natural Systems: General Causes and
      Individual Factors of the Different Bioelements.
AB  - The global isotope abundance of natural organic compounds is determined by that
      of their precursors. A prerequisite for the formation of non-statistical
      intermolecular and intramolecular isotope distributions is the occurance of
      thermodynamic and kinetic isotope effects in irreversible and branched metabolic
      processes. This coincidence permits the interference of external factors like
      climatological conditions during biosynthesis, thus leading to corresponding
      modulations of isotope fractionations. The general principles of the in-vivo
      isotope discrimination are outlined and the individual properties of the
      different bioelements in this system are described. The results are discussed in
      regard to obtain maximum information about the origin and authenticity of a
      natural compound by multielement isotope analysis.

PMID- 29016210
TI  - The Stable Isotopic Geochemistry of the Sulfur and Carbon Cycles in a Modern
      Karst Environment.
AB  - The stable isotopic geochemistry of the sulfur and carbon cycles in a modern
      karst environment at the southwest border of the Harz Mountains (Germany) has
      been studied during a 7-year period. Beside major, minor and trace elements,
      river and sulfate-carbonate ground water were analyzed for the 13C/12C ratios of
      the dissolved carbonate species, the 18O/16O ratio of water, and the 34S/32S and
      18O/16O ratios of dissolved sulfate. Additionally, the carbon, sulfur and oxygen
      isotopic composition of the major karst aquifers (carbonate and gypsum anhydrite
      rocks) of the Permian Zechstein formation was measured. Nowadays, the stable
      isotope biogeochemistry of the river and karst water in the studied area results
      from the complex interactions between dissolution of biogenic CO2 in the water
      unsaturated zone, (minor) subterrestrial microbial decomposition reactions of
      organic matter (recent DOC or fossil organic matter), interactions with carbonate
      and sulfate aquifer minerals, and input of acids from atmospheric pollution
      (e.g., sulfuric acid). Subsurface precipitation of secondary calcite due to the
      incongruent dissolution of gypsum and/or dolomite is deduced from the
      hydrogeochemical composition of selected ground waters and the isotopical
      composition of calcite found in gypsum aquifer material. Spring and river waters
      were additionally influenced by the liberation of carbon dioxide into the Earth's
      atmosphere, a process which is accompanied by the preferrential desorbtion of
      12CO2. The sulfur isotopic composition of dissolved sulfate from ground and
      spring waters indicates a mixture of sulfate derived from surface waters (mainly
      originating from atmospheric pollution) and geogenic sulfate from the subsurface
      dissolution of gypsum/anhydrite of the Zechstein formation. The oxygen isotopic
      composition of dissolved sulfate is generally far away from the exchange
      equilibrium with water, but consistent with the two-component mixing model
      derived from the sulfur isotope ratios.

PMID- 29016211
TI  - Chemical and Isotope Investigations in Dissolved Gases of a Meromictic Residual
      Lake.
AB  - Lake Hufeisen near Halle/Saale has been formed in an old mining pit. Its deepest
      part is trench shaped and filled with water of sodium chloride content. Due to
      the density difference strong mixing processes in this part of the water body are
      prevented all over the year (meromictic lake). Therefore anoxic conditions have
      been established and the organic matter of the lake sediments is converted to
      carbon dioxide and methane. Over a period of more than one year gas samples were
      collected from different water depths. The investigations of the chemical
      composition (mainly nitrogen, carbon dioxide and methane) and the carbon isotope
      ratios show different relationships for individual species. The results are
      discussed with respect to the behaviour of the gases in the water column and to
      the stability of the density stratification in the saline bottom water.

PMID- 29016212
TI  - Editorial board page for "Isotopes in Environmental and Health Studies", Volume
      35, Number 1-2.
AB  - This is a scanned image of the original Editorial Board page(s) for this issue.

PMID- 29016213
TI  - Preface.

PMID- 29016215
TI  - Assessment of the Flow Dynamic of a Mining Lake by Stable Isotope Investigations.
AB  - For water samples from mining lake ML 111 of the Lusatian Lignite District and
      surrounding aquifers delta34S(SO4-b), delta15N(NH4+), deltaD, and delta18O (H2O)
      values have been determined to asess the flow dynamic of the in- and outflow
      scenario. The high mineralization and acidification (pH > 2.6) of the lake water
      results from an intensive interaction with the surrounding dump sites and the
      inflow of extremely sulfate rich dump water (up to 4,100mg/1 SO4-). delta34S
      values range from -70/00 to + 7 degrees CDT in the inflow aquifers. The lake
      water is considered to be a mixture of different water bodies. The evaporation
      signature in the outflow aquifer suggests that the groundwater consists of 60%
      lake water. The nitrogen transfer is explained by 15N signature of ammonium.
      Sulfate reduction, perceptible in outflow and dump aquifer, cannot be proved
      within the mining lake by 34S and hydrochemistry.

PMID- 29016216
TI  - The Effect of an 15NH415NO3 Fertilization at Flowering on Growth and Nitrogen
      Fixation of White and Blue Lupins.
AB  - It is well established that legume species differ in intensity and duratio of
      nitrogen fixation during pod-filling. This was studied on new lines of white and
      blue lupins by comparing a solely nitrogen fixing and a treatment supplied with
      15N-labelled fertizlier at flowering in pot experiments. Nitrogen application at
      flowering markedly incresed seed and total dry matter and seed and total N yield
      in white lumpins but remained without effect in blue lupins. simply replacing
      nitrogen fixation. Nitrogen fixation virtually ceased with the onset of pod
      filling in white lupins, causing a massive N-remobilization from vegetative plant
      parts. In contrast, the blue lupins fixed about 70% of total nitrogen fixation
      after flowering and displayed growth and net-N-assimilation of the vegetative
      plant parts. In both species the stems and pods especially supported seed N
      filling, indicated by a low% N and a high C/N ratio at ripeness. It is concluded
      that pod-filling proved to be a critical stage for the seed yield in grain
      legumes. Exploiting differences in nitrogen fixation in this growth stage, e.g.,
      by breeding, needs more precise knowledge about the regulation mechanisms and
      source-sink relations.

PMID- 29016217
TI  - The Influence of Dung Amendments on Dissolved Organic Matter in Grassland Soil
      Leachates - Preliminary Results from a Lysimeter Study.
AB  - Understanding the carbon (C) cycle in grassland pasture systems requires more
      information about the fate of decomposing dung material within the soil. In this
      soil lysimeter study we successfully applied the natural 13C abundance labelling
      technique to trace dung-C within a temperate grassland soil. Dung was collected
      from beef steers fed on either maize (a C4 plant) or perennial ryegrass (a C3
      plant) silages, and applied to a freely draining (C3) grassland soil. Leachates
      were collected from soil lysimeters (0-2.5) and (0-10 cm soil depth) to determine
      the organic carbon and 13C content of < 0.7 MUm filtered solution. Leachates were
      taken from (i) control, no dung added, (ii) C3 dung and (iii) C4 dung amended
      soil. Results showed that, (i) the addition of dung resulted in a tenfold
      increase in C lost from the lysimeters in drainage waters, (ii) up to 50% of the
      C present in the leachates was 'native' soil C and (iii) the application of dung
      produced a 'priming' effect. Further work is required to verify; (i) whether
      increased leaching of native C following dung application is a 'true priming'
      phenomenon, or merely the result of 'displacement' or 'pool substitution' of soil
      C, and (ii) the precise conditions and mechanisms under which organic amendments
      induce a true 'priming' effect in grassland and other agricultural soils.

PMID- 29016218
TI  - Impact of Resident-Performed Laparoscopic Appendectomy on Patient Outcomes and
      Safety.
AB  - BACKGROUND: Laparoscopic appendectomy is a training model for surgical residents
      to begin their surgical experience. However, there is concern about worse
      outcomes of surgery performed by inexperienced residents. We investigated
      surgical outcomes and patient safety in laparoscopic appendectomy performed by
      residents. MATERIALS AND METHODS: This is a retrospective cohort study of all
      consecutive patients operated on for acute appendicitis in a single tertiary
      hospital. A total of 971 patients who had laparoscopic appendectomy on an
      emergency basis between December 2010 and 2014 were analyzed. An attending,
      fellow, or resident with or without supervision performed the surgery. Surgical
      outcomes were compared among the four groups according to operator type. RESULTS:
      Laparoscopic appendectomy was successfully performed in 965 patients (99.4%) and
      was converted to open surgery in 6 patients. The conversion rate and incidence of
      complications were not different among the four groups. Operating time and length
      of hospital stay were significantly shorter in the attending group than in the
      fellow or resident groups, but did not differ between the fellow and resident
      groups. Unsupervised residents or fellows more often placed abdominal drainage
      than attending surgeons. Patients with drainage had a significantly longer
      hospital stay compared to patients without drainage (3.64 days versus 6.33 days,
      P <= .0001), as well as a longer mean time to gas passage (1.17 days versus 1.61
      days, P <= .0001). CONCLUSIONS: Resident-performed laparoscopic appendectomy was
      safe, but was associated with significant prolongations in hospital stay and
      operation time. These differences were not clinically relevant with regard to
      complications.

PMID- 29016219
TI  - Emerging Zoonotic Influenza A Virus Detection in Myanmar: Surveillance Practices
      and Findings.
AB  - We describe 2-season, risk-based, virological surveillance for zoonotic avian
      influenza in Myanmar and report the first detection of influenza A subtypes H5N6
      and H9N2 in Myanmar. The study focused mainly on the live bird markets in border
      townships, where illegal poultry importation from China usually takes place. The
      objective was to enhance early warning for low pathogenic avian influenza A(H7N9)
      incursion. The study followed the guidelines of the Food and Agriculture
      Organization (FAO) of the United Nations for influenza A(H7N9) surveillance in
      uninfected countries. The sampling strategy was risk-based at all sampling
      levels. Sample collection and laboratory analysis were carried out with the
      government of the Union of the Republic of Myanmar. Laboratory testing was
      according to a previously published FAO laboratory protocol and algorithm
      designed to detect a range of influenza A subtypes. Challenges to implementation
      are outlined. The study provided evidence that the H7N9 subtype had not entered
      Myanmar but detected other subtypes, including H5N6 and H9N2. Although there were
      logistical difficulties associated with nation-related issues, the results
      highlight the importance and feasibility of this risk-based active surveillance,
      which should be urgently established in other countries, especially those located
      at the east-southeast influenza epicenter.

PMID- 29016220
TI  - Considerations for Fueling an Endurance Athlete With Home Parenteral Nutrition.
AB  - The goal of clinicians managing nutrition support for patients with home
      parenteral nutrition (HPN) is to adapt nutrition needs to best serve the
      consumers, so they may have the best quality of life despite specialized
      nutrition needs. Some HPN consumers may desire to participate in endurance
      athletics, which will require special considerations. This review is intended to
      outline key nutrition differences in endurance athletes that a nutrition support
      team should consider when providing HPN.

PMID- 29016221
TI  - Apoptotic and Immunosuppressive Effects of Turmeric Paste on 7, 12 Di Methyl Benz
      (a) Anthracene Induced Skin Tumor Model of Wistar Rat.
AB  - Dietary components with potent anticancerous property are gaining attention as
      therapeutic agents due to low cost of therapy and minimal toxic effects. Turmeric
      is one such miracle spices of Indian and South Asian recipes with multiple
      medicinal properties. The anticarcinogenic properties of its active compound
      curcumin have been studied in detail. However, studies on the medicinal
      properties of crude turmeric used as dietary agents are lacking. Therefore, in
      this study we investigated the effects of dietary and topical crude turmeric
      paste on DMBA induced skin tumor of male Wistar rats. We observed the apoptotic
      effect of crude turmeric paste on DMBA induced tumor with depletion of T cells
      response. Our results demonstrated the significant expression of major pro
      apoptotic genes like caspase-2, 3, 8, 9, PARP, and p53 and down regulation of
      major pro-inflammatory (NF-kappaB) and pro-angiogenic factors and (VEGF) in
      turmeric treated tumor tissues. We also observed significant decrease in CD4+,
      CD8+, and Natural Killer cell population as compared to the untreated group.

PMID- 29016223
TI  - Impending Carotid Blowout From a Large Neck Mass Treated Sequentially With
      Endovascular Coil Embolization Followed by Induction Chemotherapy.

PMID- 29016224
TI  - Programmed Cell Death Ligand 1-Induced Coma From Diffuse Cerebritis.

PMID- 29016222
TI  - Misidentification of transthyretin and immunoglobulin variants by proteomics due
      to methyl lysine formation in formalin-fixed paraffin-embedded amyloid tissue.
AB  - Proteomics is becoming the de facto gold standard for identifying amyloid
      proteins and is now used routinely in a number of centres. The technique is
      compound class independent and offers the added ability to identify variant and
      modified proteins. We re-examined proteomics results from a number of formalin
      fixed paraffin-embedded amyloid samples, which were positive for transthyretin
      (TTR) by immunohistochemistry and proteomics, using the UniProt human protein
      database modified to include TTR variants. The amyloidogenic variant, V122I TTR,
      was incorrectly identified in 26/27 wild-type and non-V122I variant samples due
      to its close mass spectral similarity with the methyl lysine-modified WT peptide
      [126KMe]105-127 (p.[146 KMe]125-147) generated during formalin fixation.
      Similarly, the methyl lysine peptide, [50KMe]43-59, from immunoglobulin lambda
      light chain constant region was also misidentified as arising from a rare myeloma
      derived lambda variant V49I. These processing-derived modifications are not
      present in fresh cardiac tissue, non-fixed fat nor serum and do not materially
      affect the identification of amyloid proteins. They could result in the incorrect
      assignment of a variant, and this may have consequences for the immediate family
      who will require genetic counselling and potentially early clinical intervention.
      As proteomics becomes a routine clinical test for amyloidosis, it becomes
      important to be aware of potentially confounding issues such as formalin-mediated
      lysine methylation, and how these may influence diagnosis and possibly treatment.

PMID- 29016226
TI  - Trajectories of Injectable Cancer Drug Costs After Launch in the United States.
AB  - Purpose Cancer drug prices at launch have increased in recent years. It is
      unclear how individual drug prices change over time after launch and what market
      determinants influence these changes. We measured the price trajectories of a
      cohort of cancer drugs after their launch into the US market and assessed the
      influence of market structure on price changes. Methods We studied the changes in
      mean monthly costs for a cohort of 24 patented, injectable anticancer drugs that
      were approved by the US Food and Drug Administration between 1996 and 2012. To
      account for discounts and rebates, we used the average sales prices published by
      the Centers for Medicare and Medicaid Services. Costs were adjusted to US general
      and health-related inflation rates. For each drug, we calculated the cumulative
      and annual drug cost changes. We then used a multivariable regression model to
      evaluate the association between market and cost changes over time. Results With
      a mean follow-up period of 8 years, the mean percent change in cost for all drugs
      was +25% (range, -14% to +96%). After adjusting for inflation, the mean cost
      change was +18% (range, -16% to +59%). Rituximab and trastuzumab followed a
      similar pattern in cost increases over time, and the inflation-adjusted monthly
      costs rose since approval by 49% and 44%, respectively. New supplemental US Food
      and Drug Administration approvals, new off-label indications, and new competitors
      did not influence the annual cost change rates. Conclusion Anticancer drug costs
      may change substantially after launch. Regardless of competition or supplemental
      indications, there is a steady increase in costs of patented anticancer agents
      over time. New regulations may be needed to prevent additional increases in drug
      costs after launch.

PMID- 29016225
TI  - ASCO Value Framework Highlights the Relative Value of Treatment Options in
      Ovarian Cancer.
AB  - PURPOSE: The ASCO value framework allows physicians and patients to compare the
      relative value of novel treatments. Our aim was to assess the value of three
      frontline ovarian cancer therapies by using this framework. METHODS: From phase
      III, randomized controlled clinical trial (RCT) data, the net health benefits
      (NHBs) for three frontline ovarian cancer treatment options-dose-dense paclitaxel
      (Japanese Gynecologic Oncology Group study JGOG 3016), intraperitoneal
      (IP)/intravenous (IV) chemotherapy (Gynecologic Oncology Group [GOG] study GOG
      172), and concurrent plus maintenance bevacizumab (GOG 218 and the Seventh
      International Collaborative Ovarian Neoplasm study [ICON7])-were calculated. The
      ASCO value framework calculates the NHB by using six criteria: clinical benefit,
      toxicity, tail of the curve, symptom palliation, treatment-free interval, and
      quality of life. Clinical benefit calculation uses ASCO-assigned importance
      weights for overall survival and progression-free survival. The maximum possible
      NHB points is 180. NHBs were presented alongside the drug-acquisition cost (DAC)
      of each therapy. A benefit-cost ratio of NHB points per additional cost was
      calculated. RESULTS: The NHB of dose-dense paclitaxel was 38, at an additional
      cost of $16 per cycle. IP cisplatin/IV + IP paclitaxel received 29 NHB points, at
      an additional cost of $1,629 per cycle. Concurrent plus maintenance bevacizumab
      received 24 NHB points, at an additional cost of $7,581 per cycle (GOG 218) or
      six NHB points ($3,790 per cycle; ICON7). The ratios of NHB points-to-dollar were
      as follows: dose-dense paclitaxel, 2.4 (highest); IP chemotherapy, 0.018; and
      bevacizumab, 0.003 (lowest). CONCLUSION: Using the ASCO value framework, we
      constructed value snapshots of three major frontline therapeutic options in
      ovarian cancer. Dose-dense paclitaxel provided the highest additional value when
      analysis accounted for NHB and cost. However, additional research is needed to
      include individual patient preferences and provide personalized value
      assessments.

PMID- 29016227
TI  - The Toxicity of Time.

PMID- 29016228
TI  - Pembrolizumab in Small-Cell Lung Cancer: In Search of the Best Biomarker.

PMID- 29016229
TI  - Hearing Loss.

PMID- 29016230
TI  - Antimicrobial Resistance and Genotypes of Campylobacter jejuni from Pig and
      Cattle Carcasses Isolated in Poland During 2009-2016.
AB  - Between 2009 and 2016, 317 and 529 swabs from cattle and pig carcasses,
      respectively, were collected all over Poland and tested for the presence of
      Campylobacter. Among 37 (11.7%) and 161 (30.4%) positive samples, 44
      Campylobacter jejuni isolates were detected. A total of 29 different sequence
      types (STs) and 12 various clonal complexes were identified. Antimicrobial
      resistance revealed that 17 (38.6%) C. jejuni (10 from cattle and 7 from pig
      carcasses, respectively) were susceptible to all antimicrobials used in the
      study, whereas the remaining 27 (61.4%) isolates (12 from cattle and 15 from
      pigs, respectively) were resistant to at least one antimicrobial agent, mainly to
      quinolones (23 out of 44 isolates; 52.3%) and tetracyclines (14 strains; 31.8%).
      Only one isolate from cattle and two from pigs displayed resistance to
      streptomycin, and none of C. jejuni tested was resistant to erythromycin and
      gentamicin. All isolates with STs, ST356, ST443, ST464, ST658, ST2036, and
      ST6411, as well as some isolates belonging to ST257 and ST1947, were resistant to
      quinolones and tetracyclines. The results show that cattle and pigs may be a
      reservoir of quinolone and tetracycline resistant C. jejuni with STs which were
      previously isolated from humans with campylobacteriosis.

PMID- 29016231
TI  - Parenteral and Enteral Nutrition-From Hospital to Home: Will It Be Covered?
AB  - With scientific advances allowing for the safe delivery of parenteral and enteral
      nutrition in the home setting, challenges have risen with determining how this
      will be financially feasible for patients. In the United States, the government
      is one of the major payers for home parenteral and enteral nutrition (HPEN).
      Thus, it is important for nutrition providers to have an understanding of the
      Medicare criteria that must be met in order for these services to be covered. It
      can be difficult for clinicians to sift through these requirements and decipher
      for whom and when HPEN is covered. As our nutrition science knowledge and
      delivery continue to grow and evolve, potential barriers to this coverage may
      arise. This article provides background on those currently on HPEN in the United
      States, the current Medicare HPEN coverage criteria, and challenges we may face
      in the future.

PMID- 29016232
TI  - Algorithm for the management of asthma in pregnant women: a protocol to optimize
      processes in healthcare.
AB  - INTRODUCTION: Asthma is the most common chronic disease in pregnant women. Its
      evolution during pregnancy could improve, stay the same or worsen, especially in
      cases where there is a loss of clinical control. This can lead to maternal and
      fetal hypoxia with serious adverse perinatal outcomes. Areas covered: This
      article reviews physiological modifications in pregnancy, effects of pregnancy on
      asthma, and possible consequences on fetus development. Furthermore, it reviews
      evidence on assessment and both pharmacological and non-pharmacological
      management of asthma in pregnant and breastfeeding women as well as in acute
      exacerbations. Electronic databases, such as PUBMED, were searched for terms
      pregnan* or perinat* or obstet* and breastfeeding or asthma or wheeze, as well as
      a book published by the present authors. Expert commentary: A patient-centered
      multidisciplinary approach, where the respiratory specialists have a key role in
      assessing and achieving control, as well as the education interventions for self
      monitoring and adherence are at least as important as adequate pharmacological
      treatment.

PMID- 29016233
TI  - Metabolic Complications of Home Parenteral Nutrition.
AB  - Home parenteral nutrition (HPN) has benefited countless patients since its
      initiation almost 5 decades ago. Over time, HPN has been found to be associated
      with various complications, including metabolic disorders. Metabolic
      complications can be grouped into short-term (eg, fluid imbalance, electrolyte
      disturbances, glucose abnormalities) and long-term (eg, hepatobiliary disorders,
      metabolic bone disease, iron deficiency anemia, manganese toxicity) categories.
      There are a number of treatment options for each complication. It is important to
      evaluate the entire clinical picture prior to initiating an intervention and use
      evidence-based interventions when available. A dedicated multidisciplinary team
      is best suited to prevent and manage complications when they are identified.

PMID- 29016235
TI  - Telemedicine Support Groups for Home Parenteral Nutrition Users.
AB  - Patients receiving home parenteral nutrition (HPN), a life-sustaining intravenous
      (IV) infusion that provides nourishment and hydration to patients with short gut
      or inflammatory bowel diseases, are often isolated and not in visual contact with
      peers or health providers. One completed clinical trial (Clinical Trials.gov
      NCT0190028) and 1 ongoing clinical trial (Clinical Trials.gov NCT02987569) are
      evaluating a mobile videoconferencing-delivered support group intervention for
      patients on HPN and their caregivers. This home-based telemedicine intervention
      uses encrypted tablet-based videoconferencing to connect multiple families in
      real time. The twice-daily IV regimen is challenging for patients who may
      experience infusion catheter-related bloodstream infections, difficulties with
      fatigue, loss of sleep, depressive disorders, and worry over the potential life
      threatening side effects and the expenses of this therapy. Using secure
      telemedicine, the facilitated support group intervention aims to enhance HPN home
      care, daily functioning, and quality of life. The authors provide the rationale
      for the telemedicine approach with HPN users and caregivers. They provide "how
      to" information about the content and process of the facilitated support group
      sessions via secure videoconferencing. They share lessons learned from the
      ongoing evaluation of the telemedicine approach.

PMID- 29016234
TI  - Limited Evidence Suggests a Protective Association Between Oral Contraceptive
      Pill Use and Anterior Cruciate Ligament Injuries in Females: A Systematic Review.
AB  - CONTEXT: Female athletes aged 14 to 18 years are at particular risk for anterior
      cruciate ligament (ACL) injuries. Hormonal factors are thought to predispose them
      to this injury. Oral contraceptive pills (OCPs) might reduce ACL injury risk,
      although the literature appears controversial. OBJECTIVE: To evaluate the
      association between OCP use and ACL injuries in women. The secondary objective
      was to determine the rates of ACL injuries in the pre- and postovulatory phases
      of the menstrual cycle in OCP and non-OCP (NOCP) users. DATA SOURCES: Searches
      were performed across 4 reference databases (PubMed, CINAHL, Embase, Cochrane),
      abstracts from 6 specialty societies, ClinicalTrials.gov , and reference lists of
      relevant papers. STUDY SELECTION: We included studies investigating the
      association between OCP use and ACL injuries in females of any age or the
      distribution of ACL injuries across the menstrual cycle in OCP and NOCP users.
      STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 3. DATA EXTRACTION:
      Data regarding study design, population characteristics, OCP details, outcome
      definitions, analytic methods, and results were extracted from the included
      studies. The methodological quality of each study was assessed using the
      Newcastle-Ottawa scale. RESULTS: The search yielded 1305 citations, of which 7
      retrospective observational studies met the inclusion criteria. Two large case
      control studies with higher methodological quality suggested that OCP use may
      reduce the risk of sustaining an ACL injury. Five comparative studies examining
      injury distribution across the menstrual cycle in OCP and NOCP users had
      conflicting findings, were heterogeneous, and were limited by low methodological
      quality. CONCLUSION: The evidence suggests OCP use may reduce the risk of ACL
      injury; however, no conclusions can be drawn regarding differences in risk of ACL
      injuries between OCP and NOCP users across the menstrual cycle. Studies were
      limited by small sample sizes, heterogeneity, and methodological concerns.

PMID- 29016236
TI  - Effects of 445-nm Diode Laser-Assisted Debonding of Self-Ligating Ceramic
      Brackets on Shear Bond Strength.
AB  - OBJECTIVE: The aim of this study was to measure the effect of irradiation with a
      novel 445-nm diode laser on the shear bond strength (SBS) of ceramic brackets
      before debonding. MATERIALS AND METHODS: Thirty ceramic brackets (In-Ovation(r)
      C, GAC) were bonded in standard manner to the planed and polished buccal enamel
      surfaces of 30 caries-free human third molars. Each tooth was randomly allocated
      to the laser or control group, with 15 samples per group. The brackets in the
      laser group were irradiated with the diode laser (SIROLaser Blue(r); Sirona) on
      three sides of the bracket bases for 5 sec each (lateral-coronal-lateral, a total
      of 15 sec) immediately before debonding. SBS values were measured for the laser
      group and control group. To assess the adhesive remnant index (ARI) and the
      degree of enamel fractures, micrographs of the enamel surface were taken with 10
      fold magnification after debonding. RESULTS: The SBS values were significantly
      lower statistically in the laser group in comparison with the control group (p <
      0.05). The ARI scores were also significantly lower statistically in the laser
      group in comparison with the control group (p < 0.05). No bracket fractures or
      enamel fractures occurred in either group after debonding. CONCLUSIONS:
      Irradiation of ceramic brackets with the novel diode laser before debonding
      significantly reduces the SBS values. This is of clinical importance, as it means
      that the risk of damage to the teeth, bracket fractures, and the overall
      treatment time can be reduced.

PMID- 29016237
TI  - Actual competence, rather than perceived competence, is a better predictor of
      physical activity in children aged 6-9 years.
AB  - There is a limited understanding about the relative importance of perceived and
      actual competence on emergent physical activity levels in children and whether
      there is a difference in their development and strength between boys and girls.
      This study used a single-cohort, multiple age group design to monitor physical
      activity, actual motor competence (AMC) and perceived competence (PC) on four
      occasions over 18 months in 6-to 9-year-old boys and girls (N = 201). Physical
      activity was measured by 7-day daily step counts (pedometer) and activity diary.
      AMC was assessed by mastery of skill criteria for 4 motor skills; run, overhand
      throw, standing broad jump, and line walk. PC was measured with the Self
      Description Questionnaire-I. Linear Mixed Model analysis revealed that AMC,
      Gender and School significantly impacted physical activity levels longitudinally
      in these children. AMC made a greater contribution (9-30%) to physical activity
      levels than PC (0-5%), and at an earlier age in boys (7 years) than girls (9
      years). The need to acknowledge these developing distinctions in considering
      emergent physical activity levels has important implications for childhood
      learning environments and physical activity interventions.

PMID- 29016238
TI  - Outstanding Challenges in Scientific Research on Mindfulness and Meditation.
AB  - Van Dam et al. raise a number of critical issues in contemporary research on
      mindfulness and meditation and offer a prescriptive agenda for future work in
      this area. While we agree with all of the key points made in their article, there
      are a number of important issues omitted that are central to a comprehensive
      agenda for future research in this area. This commentary highlights five key
      points: (a) Many of the key methodological issues the article raises are not
      specific to research on mindfulness; (b) contemplative practices are varied, and
      the landscape of modern scientific research has evolved to focus almost
      exclusively on one or two types of practice to the exclusion of other forms of
      practice that are potentially highly impactful;

PMID- 29016239
TI  - Early distinction between shame and guilt processing in an interpersonal context.
AB  - Shame and guilt have been compared in many behavioral and functional magnetic
      resonance imaging studies. However, the time course of shame and guilt processing
      remains unknown. We conducted an event-related potential (ERP) study to
      investigate the temporal dynamics of shame and guilt in an interpersonal context.
      Behaviorally, participants reported "shame" when their wrong advice was correctly
      rejected by a confederate, whereas reported "guilt" when their wrong advice
      resulted in economic loss of a confederate. The ERP results showed significant
      difference between the shame and guilt conditions in the early P2 component (140
      220 ms) over the frontal region and the alpha oscillations (240-1000 ms) over the
      parietal region. No significant difference was found between the shame and guilt
      conditions in the N2, P3, and theta oscillations. These results supported
      previous findings that shame compared to guilt involves more self-referential
      processing, whereas guilt compared to shame involves more empathetic processing,
      and provided evidence that the distinction between shame and guilt could occur in
      an early stage.

PMID- 29016241
TI  - Analysing a cycling grand tour: Can we monitor fatigue with intensity or load
      ratios?
AB  - This study evaluated the changes in ratios of different intensity (rating of
      perceived exertion; RPE, heart rate; HR, power output; PO) and load measures
      (session-RPE; sRPE, individualized TRIMP; iTRIMP, Training Stress ScoreTM; TSS)
      in professional cyclists. RPE, PO and HR data was collected from twelve
      professional cyclists (VO2max 75 +/- 6 ml?min?kg-1) during a two-week baseline
      training period and during two cycling Grand Tours. Subjective:objective
      intensity (RPE:HR, RPE:PO) and load (sRPE:iTRIMP, sRPE:TSS) ratios and
      external:internal intensity (PO:HR) and load (TSS:iTRIMP) ratios were calculated
      for every session. Moderate to large increases in the RPE:HR, RPE:PO and sRPE:TSS
      ratios (d = 0.79-1.79) and small increases in the PO:HR and sRPE:iTRIMP ratio (d
      = 0.21-0.41) were observed during Grand Tours compared to baseline training data.
      Differences in the TSS:iTRIMP ratio were trivial to small (d = 0.03-0.27). Small
      to moderate week-to-week changes (d = 0.21-0.63) in the PO:HR, RPE:PO, RPE:HR,
      TSS:iTRIMP, sRPE:iTRIMP and sRPE:TSS were observed during the Grand Tour.
      Concluding, this study shows the value of using ratios of intensity and load
      measures in monitoring cyclists. Increases in ratios could reflect progressive
      fatigue that is not readily detected by changes in solitary intensity/load
      measures.

PMID- 29016240
TI  - Reiterated Concerns and Further Challenges for Mindfulness and Meditation
      Research: A Reply to Davidson and Dahl.
AB  - In response to our article, Davidson and Dahl offer commentary and advice
      regarding additional topics crucial to a comprehensive prescriptive agenda for
      future research on mindfulness and meditation. Their commentary raises further
      challenges and provides an important complement to our article. More
      consideration of these issues is especially welcome because limited space
      precluded us from addressing all relevant topics. While we agree with many of
      Davidson and Dahl's suggestions, the present reply (a) highlights reasons why the
      concerns we expressed are still especially germane to mindfulness and meditation
      research (even though those concerns may not be entirely unique) and (b) gives
      more context to other issues posed by them. We discuss special characteristics of
      individuals who participate in mindfulness and meditation research and focus on
      the vulnerability of this field inherent in its relative youthfulness compared to
      other more mature scientific disciplines. Moreover, our reply highlights the
      serious consequences of adverse experiences suffered by a significant subset of
      individuals during mindfulness and other contemplative practices. We also
      scrutinize common contemporary applications of mindfulness and meditation to
      illness, and some caveats are introduced regarding mobile technologies for
      guidance of contemplative practices.

PMID- 29016242
TI  - Early Predictors of Abscess Development after Perforated Pediatric Appendicitis.
AB  - BACKGROUND: Approximately one-third of children with appendicitis present with
      advanced disease or perforation. Whereas this increases the risk for post
      operative complications and re-admission, it is not yet possible to predict early
      on who will develop an abdominal abscess. We sought to identify specific risk
      factors for this complication, in an attempt to streamline post-operative care.
      PATIENTS AND METHODS: We reviewed the records of all cases of perforated
      appendicitis over a 12-month period at a tertiary children's hospital. All
      patients who developed an abscess despite treatment minimum of seven days of
      antibiotic therapy were identified. Patients who presented or were re-admitted
      with an abscess were excluded from analysis. Records were reviewed for
      demographics, laboratory results, progression of oral intake, and vital signs.
      RESULTS: Of 273 patients with appendicitis, we identified 59 cases of perforated
      appendicitis. Fifteen patients were excluded. Eight of the remaining 44 patients
      (18.2%) developed an abscess during their initial admission. Their mean length of
      stay was longer than that of patients without an abscess (13.4 +/- 7.1 vs. 6.9 +/
      1.9 d, p < 0.0001). Gender, leukocytosis, or diarrhea at presentation, maximum
      temperature on post-operative day 3, and maximum heart rate on post-operative day
      3 were not statistically different. Diet progression was different between the
      two groups: none of the 21 patients who were tolerating a regular diet by post
      operative day 3 developed an abscess, compared with 8 of the 23 patients who were
      not yet eating a regular diet on post-operative day 3 (p < 0.01). Late
      leukocytosis also correlated with the presence of an abscess: 7 of the 8 patients
      with an abscess had persistent leukocytosis at days 5 through 7, compared with 3
      of 31 patients without abscess (p < 0.05). An ultrasound was obtained for these 3
      patients and proved normal. CONCLUSIONS: Tolerating a regular diet three days
      after appendectomy for perforated appendicitis decreased the likelihood of a post
      operative abscess. No other parameter was predictive of this complication early
      in the post-operative period. If confirmed in a larger prospective study, this
      finding may help decrease the length of stay for low-risk patients, and identify
      abscesses in high-risk patients in a timely fashion.

PMID- 29016243
TI  - Safety and Tolerability of Laser Hair Depilation in Pilonidal Disease: A Pilot
      Study.
AB  - BACKGROUND: Pilonidal disease is a common and painful disorder that can be
      challenging to manage. Recurrent surgical treatment is often warranted and may
      result in significant morbidity, with reported wound complication rates as high
      as 30%. Laser hair depilation of the natal cleft may decrease the incidence of
      recurrence. The purpose of this study was to assess the safety and tolerability
      of laser hair depilation in adolescents with pilonidal disease. METHODS: We
      performed a prospective, single arm, pilot trial of laser hair depilation to the
      natal cleft in 13 patients with pilonidal disease. Each patient received an
      outpatient laser depilation treatment every four weeks with a goal of five total
      treatments. Follow-up tolerability was measured after each treatment by obtaining
      Likert scale, patient-reported, pain scores immediately after laser treatment and
      every six hours post-treatment, for the first 24 hours. Consistent pain scores <4
      were used as a proxy for tolerability. The primary end point was tolerability and
      safety, defined as pain scores consistently <4 and no deep second-degree burns
      during the 24-hour post-treatment period. The secondary end point was disease
      recurrence at one year. RESULTS: Thirteen patients were enrolled with 12 patients
      completing five laser depilation treatment sessions and one patient completing
      only four. There was 100% tolerability of treatments with no occurrence of second
      degree burns. No patient was unable to complete a treatment session because of
      discomfort. Significantly diminished hair growth was noted after three
      treatments. All 13 patients were recurrence-free at a median follow-up of 13
      months post-treatment initiation. CONCLUSIONS: Laser hair depilation is safe and
      well tolerated in adolescents with pilonidal disease and may be effective at
      decreasing pilonidal disease recurrence. A prospective randomized controlled
      trial is planned to determine effectiveness of laser hair depilation compared
      with chemical/mechanical depilation methods in preventing pilonidal disease
      recurrence.

PMID- 29016244
TI  - Measuring limitations in activities of daily living: a population-based
      validation of a short questionnaire.
AB  - PURPOSE: A newly developed questionnaire assessing limitations in activity of
      daily living (LADL-Q) that should improve assessment of LADL is tested in a large
      population-based validation study. METHODS: This survey was paper-based. Overall,
      16,634 individuals who were representative of the working population in the
      German-speaking part of Switzerland participated in the study. Item analysis was
      used the final version of the LADL-Q to four items per subscale that correspond
      to potential problems in three body regions (back and neck, upper extremities,
      lower extremities). Analysis included tests for reliability, internal
      consistency, dimensionality and convergent validity. RESULTS: Test-retest
      reliability coefficients after 2 weeks ranged from 0.82 to 0.99 (Mdn = 0.87),
      with no item having a coefficient below 0.60. The median item-total coefficients
      ranged between moderate and good. Correlation coefficients between LADL-Q
      subscales and three validated clinical instruments (Western Ontario and McMaster
      Universities osteoarthritis index, shoulder pain disability index, Oswestry)
      ranged from 0.63 to 0.81. In structural equation modeling the three subscales
      were significantly related with two important outcomes in occupational
      rehabilitation: self-reported general health and daily task performance.
      CONCLUSION: The new LADL-Q is a brief, reliable and valid tool for assessment of
      LADL in studies on musculoskeletal health.

PMID- 29016245
TI  - Effect of a high dosage opioid prior authorization policy on prescription opioid
      use, misuse, and overdose outcomes.
AB  - BACKGROUND: High dosage opioid use is a risk factor for opioid-related overdose
      commonly cited in guidelines, recommendations, and policies. In 2012, the Oregon
      Medicaid program developed a prior authorization policy for opioid prescriptions
      above 120 mg per day morphine equivalent dose (MED). This study aimed to evaluate
      the effects of that policy on utilization, prescribing patterns, and health
      outcomes. METHODS: Using administrative claims data from Oregon and a control
      state (Colorado) between 2011 and 2013, difference-in-differences analyses were
      used to examine changes in utilization, measures of high risk opioid use, and
      overdose after introduction of the policy. Opioid utilization in a cohort of
      individuals who were high dosage opioid users before the policy was also
      evaluated. RESULTS: Following implementation of Oregon's high dosage policy, the
      monthly probability of an opioid fill over 120 mg MED declined significantly by
      1.7 percentage points (95% confidence interval [CI]; -2.0% to -1.4%), whereas it
      increased significantly by 1.0 percentage points (95% CI 0.4% to 1.7%) for opioid
      fills < 61 mg MED. Fills of medications used to treat neuropathic pain also
      increased by 1.2 percentage points (95% CI 0.7% to 1.8%). The monthly probability
      of multiple pharmacy use declined by 0.1 percentage points (-0.2% to -0.0)
      following the prior authorization, but there were no significant changes in ED
      encounters or hospitalizations for opioid overdose. Among individuals who were
      using a high dosage opioid before the policy, there was a 20.3 percentage point
      (95% CI -15.3% to -25.3%) decline in estimated probability of having a high
      dosage fill after the policy. CONCLUSIONS: Oregon's prior authorization policy
      was effective at reducing high dosage opioid prescriptions. While multiple
      pharmacy use also declined, no changes in opioid overdose were observed.

PMID- 29016247
TI  - FROM THE EDITOR.

PMID- 29016246
TI  - Cognitive Dysfunction and Single Nucleotide Polymorphisms in Hepatitis C Virus
      Infected Persons: A Systematic Review.
AB  - The aim of this study was to realize a systematic review to identify data
      reported in the literature involving people infected by hepatitis C virus (HCV)
      with cognitive dysfunctions and single nucleotide polymorphisms (SNPs). The
      research was realized in six databases and the selection of studies was performed
      in two stages. Initially, we searched indexed articles from the following
      electronic databases: SciELO, MEDLINE, PubMed, HighWire, LILACS, and
      ScienceDirect. Then the articles were completely read and those that did not meet
      the eligibility criteria were excluded. Therefore, 5,669 articles were obtained
      and, of these, 25 were selected. Finally, one article involving people with HCV
      and cognitive impairment was included in the review. The frequency of the APOE-E4
      allele in people with HCV and mild liver disease was significantly lower in those
      with work memory impairment (p = 0.003) and attention (p = 0.008). This situation
      differs from other studies that showed an association between E4 allele high
      frequency and cognitive decline. Thus, studies with larger samples involving
      people with HCV, cognitive alterations, and SNPs are necessary, in view of the
      lack of this theme in the literature and the divergences in the findings.

PMID- 29016250
TI  - Scrutinizing Homophobia: A Model of Perception of Homosexuals in Russia.
AB  - We aimed to develop and validate a model of associations of perceived threat of
      homosexuals with lay beliefs about causes of homosexuality, group entitativity of
      homosexuals, approval of social action strategies targeting homosexuals, and
      support for their rights using original Russian-language measures. We tested the
      model in two samples of social network users (n = 1,007) and student respondents
      (n = 292) using structural equation modeling and path analysis. Attribution of
      homosexuality to social causes was a positive predictor of perceived threat of
      homosexuals, whereas biological causes showed an inverse effect. Perceived threat
      predicted approval of discriminatory strategies targeting homosexuals and lack of
      support for their rights and fully mediated the effects of causal beliefs on
      these variables. Group entitativity of homosexuals was a positive predictor of
      perceived threat and a significant moderator of its effects on support for
      punishment and medical treatment of homosexuals. We discuss the findings with
      reference to the Russian social context.

PMID- 29016249
TI  - Factors associated with obesity and metabolic syndrome in ageing black South
      African women.
AB  - BACKGROUND: The incidence of obesity and related metabolic diseases is high and
      increasing in sub-Saharan African women. Evidence on the determinants of these
      diseases is limited, particularly in black South African women. OBJECTIVE: This
      PhD review attempts to understand the determinants of obesity and metabolic
      syndrome (MetS) in a population of ageing urban-dwelling black South African
      women. METHODS: Drawing on the longitudinal Birth-to-Twenty-Plus cohort, data
      were collected in 2002/03 and 2012/13, including information on behavioural
      factors (smoking, sitting time, physical activity, smokeless tobacco, and alcohol
      consumption), body-size perception, body composition (measures of adiposity and
      lean mass), blood pressure, and cardiometabolic biomarkers (lipid profile,
      fasting insulin, fasting blood glucose, insulin resistance, leptin, and
      adiponectin). RESULTS: The prevalence of obesity and related cardiovascular
      disease risk was high and increased significantly over the 10 year period.
      Despite most of the study population being physically active, sitting time was
      high and associated with elevated blood pressure and hypertriglyceridaemia. Two
      groups of people were observed, those who were happy and those who were unhappy
      with their body size. In logistic regression analysis, the risk of MetS was
      lowered by abdominal subcutaneous adipose tissue and adiponectin, and increased
      by age, smoking, truncal lean mass, and insulin resistance. CONCLUSIONS: Obesity
      was confirmed to be increasing in black South African women, despite most women
      being sufficiently active according to guidelines of >=150 min activity/week.
      Nevertheless, the contribution of sitting time to poor health outcomes is evident
      in this study population and must be addressed, particularly in women who are
      content with being obese. The novel finding of the effects of abdominal
      subcutaneous tissue and truncal lean mass with MetS requires further
      investigation. The protective effect of adiponectin against MetS is an important
      finding which highlights the novel interaction between adiposity and
      cardiometabolic diseases in black South African women.

PMID- 29016252
TI  - Nursing Facility and Home and Community Based Service Need Criteria in the United
      States.
AB  - Over the past two decades states have expanded the delivery of long term care
      from institutions to the home and community. Although state Medicaid need
      criteria for the home and community based services (HCBS) waiver program must be
      equivalent to those for nursing facility (NF) criteria, other screening
      procedures for these services are not specified. This study examined variations
      in need criteria, methods for determining need, and assessment forms for NF and
      HCBS across the states, and identified whether these procedures were more
      stringent for HCBS than for NFs. The NF minimum need criteria was most often (31
      states) based on a combination of nursing, medical, functional, or other
      psychosocial criteria, 10 states used nursing criteria, and 10 states used
      limitations in functional activities criteria. The method used for determining
      need for NF was based on explicit criteria in 25 states, point systems in seven
      states, and 19 states used guidelines that allowed for judgment by those
      conducting the assessment. The average length of a NF assessment form was six and
      one-half pages, which was four pages shorter than the average HCBS form. Within
      some states the HCBS waivers have higher need criteria, more comprehensive need
      determination, and longer assessment forms than NFs. Wide variability in
      screening procedures creates potential inequities to LTC services across the
      states. Within states, more restrictive screening procedures for HCBS than for NF
      may limit access to community based long term care.

PMID- 29016251
TI  - Addressing the problem of obesity and associated cardiometabolic risk in black
      South African women - time for action!
AB  - The PhD thesis of Gradidge, entitled 'Factors associated with obesity and
      metabolic syndrome in an ageing cohort of black women living in Soweto,
      Johannesburg (Study of Women in and Entering Endocrine Transition [SWEET])',
      attempts to understand the determinants of obesity and metabolic syndrome (MetS)
      in a population of urban-dwelling black South African women. A conceptual
      framework is presented, which positions obesity as the central risk factor for
      MetS, and includes the possible influence of socioeconomic status, lifestyle
      behaviours and body size perceptions, as key determinants of obesity. This
      commentary focuses on the two main findings of Gradidge's thesis, namely, (i)
      physical activity and sedentary behaviour, and (ii) body composition and
      adiponectin, as risk factors for obesity and MetS in black South African women.
      Despite a high prevalence of obesity (48%), Gradidge showed that 75% of the women
      taking part in the study were meeting WHO guidelines on physical activity. This
      commentary suggests that the relationship between physical activity and
      cardiometabolic risk may be confounded by socioeconomic status. Alternatively,
      the intensity, and not necessarily the volume, of activity, as well as high rates
      of sedentary behaviour are posited as important determinants of obesity and MetS
      in black South African women. Accordingly, this commentary questions the veracity
      of the WHO guidelines on physical activity in developing countries, where most
      women meet the guidelines but have very poor cardiorespiratory fitness, are obese
      and are at high risk of MetS. Gradidge also showed that the most consistent and
      significant correlate of MetS in this cohort of middle-aged women was low serum
      levels of adiponectin. This commentary highlights various lifestyle interventions
      that have been shown to increase adiponectin levels. Finally, the importance of
      immediate action to address the problem of obesity and MetS is emphasised.

PMID- 29016253
TI  - 'You Need Them to Know Your Ways': Service Users' Views About Valued Dimensions
      of Home Care.
AB  - Dominant approaches to evaluating supportive home care tend to be 'top-down,'
      undertaken from the vantage points of funding bodies and professionals, rather
      than from the perspectives of service users. A longitudinal, qualitative study of
      women receiving home care in Ontario, Canada explored their accounts of what
      constitutes good and responsive care. Participants identified four dimensions of
      care that they particularly valued: Minimized exposure, being known, staying in
      charge, and being able to speak. The implications of their perspectives for home
      care practice, evaluation and organization are discussed.

PMID- 29016254
TI  - Using a Focus Group Methodology to Gain Input from People Who Use Home and
      Community Based Services.
AB  - Gaining input from people who use home and community based services is important
      for determining the usefulness of services and clarifying future direction. Many
      of the commonly used methods have drawbacks when gaining input from people
      served. The current paper describes a focus group process that has been used to
      gain input from people who use home and community based services. The focus group
      process included designing the focus groups, their implementation, and feedback
      to stakeholders. Insights are presented and have implications for home and
      community based administrators, providers, and health care specialists.

PMID- 29016255
TI  - A Study of Reliability and Burden of Home Health Assessment Using OASIS.
AB  - The Outcome and Assessment Information Set (OASIS) is used for outcome reporting,
      quality improvement, and case mix adjustment of per-episode payment for home
      health care. The research described here addresses interrater reliability of
      OASIS items and compares clinician time required to complete patient assessment
      with and without OASIS. Interrater reliability for OASIS data items was estimated
      using independent assessments by two clinicians for a sample of 66 patients.
      Incremental assessment time due to OASIS was estimated using interview data from
      two agency-matched groups of clinical care providers-one group who used OASIS in
      the assessment and a second group whose assessment did not include OASIS items.
      Interrater reliability is excellent (kappa > .80) for many OASIS items and
      substantial (kappa > 0.60) for most items. The reported time required to complete
      an assessment with OASIS did not differ from the time required for a comparable
      assessment without OASIS. The results of this study are being used to guide
      developmental efforts to improve OASIS items. They can also be informative to
      home health care agencies when interpreting OASIS-based outcome and case mix
      reports.

PMID- 29016256
TI  - The Impact of the Senior Companion Program on Quality of Life Outcomes for Frail
      Older Adults and Their Families.
AB  - The Senior Companion Quality of Care Evaluation assessed the impact of a
      federally funded senior volunteer program on quality of life outcomes for frail
      clients and their families. Telephone interviews were conducted with national
      samples of frail Senior Companion Program (SCP) clients, family members, and
      comparison group participants. Multivariate procedures were used to examine study
      outcomes. SCP clients benefited significantly from the program at 3 months,
      though fewer positive effects were reported at 9 months. SCP family members
      benefited only modestly from the program. The SCP has been considered a low-cost
      way of matching the needs of community-based frail older adults with the skills
      of senior volunteers. Now, it has been shown to have some favorable effects on
      client well-being. These findings may take on greater significance given the
      desire to expand the SCP through the USA Freedom Corps Initiative.

PMID- 29016258
TI  - Issues in Mental Health Nursing.

PMID- 29016257
TI  - Intentional Switching Between Bimanual Coordination Patterns.
AB  - Previous theoretical and empirical work indicates that intentional changes in a
      bimanual coordination pattern depends on the stability of the bimanual
      coordination pattern (Kelso, Schotz, & Schoner, 1988; Scholz & Kelso, 1990). The
      present experiments retest this notion when online Lissajous displays are
      provided. Switching to and from in-phase and antiphase and to and from 90 degrees
      and 270 degrees  were tested in Experiment 1. Participants were able to very
      effectively produce the 180 degrees , 90 degrees , and 270 degrees  coordination
      patterns although performance of the in-phase coordination task was even more
      stable. The data indicated that switching to in-phase from antiphase was more
      rapid than vice versa and that switching times between 90 degrees  to 270 degrees
      were similar. Experiment 2 investigated switching between 1:2 and 2:1 bimanual
      coordination patterns. The results indicated that switching time was similar
      between the 2:1 and 1:2 coordination tasks and that increases in stability over
      practice resulted in additional decreases in switching times. This provides
      additional evidence that the attractor landscape is fundamentally different
      dependent on the type of information provided the performer. What remains to be
      done is to reconcile these results with the various theories/perspectives
      currently used to describe and explain bimanual coordination.

PMID- 29016260
TI  - Antidepressants for Treating Depression in Adults with End-stage Kidney Disease
      with Dialysis.

PMID- 29016261
TI  - "Sound Health: Music and the Mind": The New Initiative of the National Institutes
      of Health and National Endowment for the Arts.

PMID- 29016263
TI  - A complete dynamic model of primary sedimentation.
AB  - A dynamic mathematical model for the primary clarifier of a wastewater treatment
      plant is described, which is represented by a general tanks-in-series model, to
      simulate insufficient mixing. The model quantifies successfully the diurnal
      response of both the suspended and dissolved species. It is general enough, so
      that the values of the parameters can be replaced with those applicable to a
      specific case. The model was verified through data from the Biological Centre of
      Metamorfosi, in Athens, Greece, and can be used to assist in the design of new
      plants or in the analysis and output predictions of existing ones.

PMID- 29016262
TI  - Association of 5-HTTLPR Polymorphism with the Nursing Diagnoses and the
      Achievement of Nursing Outcomes in Patients with Major Depression.
AB  - The aim of this study is to investigate whether a 44-base-pair insertion/deletion
      polymorphism in the upstream regulatory region of the serotonin transporter gene
      (5-HTTLPR) is associated with the nursing diagnoses and the achievement of the
      desired nursing outcomes in inpatients with major depression. Thirty five
      patients were evaluated. The nursing diagnoses of risk for suicide and imbalanced
      nutrition are reported less often in homozygotes of the high-expressing gene
      (LA). Carriers of the low-expressing genes (LG or S) have a worse response to
      interventions which aim to increase low self-esteem, indicating that they may
      need more intensive care in order to achieve the desired outcome. Genetics in
      psychiatric nursing could help refine personalized care, however further studies
      with large sample sizes and multiple gene evaluations are needed.

PMID- 29016264
TI  - Effect of stormwater runoff on metal distribution in the sediment and
      interstitial waters of an urban river.
AB  - Metals were analysed in the interstitial waters and sediments of an urban river,
      receiving stormwater and combined sewer overflow, over a two month period and
      interpreted in terms of rain events. Depth profiles for metal concentrations
      showed the highest interstitial water concentrations in samples with low
      sedimentary organic material. Storm events can both resuspend sediments and
      associated metal-rich interstitial waters and alter the metal distribution
      between interstitial water and sediment. Metal profiles downstream of a combined
      sewer overflow showed elevated interstitial water concentrations compared to an
      upstream site. Downstream sites also reveal evidence of metal burial and
      resuspension processes during and between wet periods.

PMID- 29016265
TI  - Toxic effects of dredged sediments of Hong Kong coastal waters on clams.
AB  - The present project is an attempt to study the effects of the sediments collected
      from various sites on the survival of three indigenous bivalves (Circe scripta,
      Gafrarium fumidum and Tapes philippinarium). The preliminary trial revealed that
      T. philippinarium was more sensitive than the other two species in response to
      the dredged sediment collected from the pollution blackspot: Yau Ma Tei typhoon
      shelter. A subsequent experiment used T. philippinarium to assess the toxicity of
      sediments under different dissolved oxygen regimes (7.8, 8.0 and 8.2 mg L-1).
      Significant correlations (p<0.05) were noted between the mortality rates of the
      test animals and the total nitrogen and ammonia contents in the seawater.

PMID- 29016266
TI  - Retention capacity of dry soils for NAPLs.
AB  - Retention capacity values were measured in the laboratory for three non-aqueous
      phase liquids (NAPLs), PCE, TCE and gasoline. The dry soils studied were sandy
      loam, clay, organic top soil and peat moss. For the conditions tested, it was
      determined that the retention capacity increased with an increase in the NAPL's
      density and the soil's porosity and a decrease in the soil bulk density. The
      largest observed retention capacity was for peat moss and PCE at approximately 7
      gg-1. A simple model was developed to correlate the findings and allow estimation
      of the retention capacity values for different soils and NAPLs. Applications of
      the retention capacity model are illustrated with typical examples.

PMID- 29016267
TI  - Treatment of variable and intermittently flowing wastewaters.
AB  - The biological treatment of wastewaters originating from hotels and residential
      areas of seasonal use, flowing intermittently, is difficult due to the fact that
      bacteria cannot survive during periods of no-flow. An investigation has been
      conducted in order to develop a system which will be able to overcome the
      difficulties encountered. After a long investigation the following system has
      given satisfactory results. The wastewater was taken initially into an aeration
      tank operating as a sequential batch reactor. Waste was taken after the
      sedimentation phase of the reactor into a coagulation-flocculation tank where it
      was treated by chemical means, and then settled in order to separate the floes.
      When the population of bacteria in the aeration tank reached the required level,
      the physico-chemical treatment was terminated and the tank used for chemical
      treatment has been started to be used as an equalization tank while the aeration
      and sedimentation tanks have been used as an activated sludge unit. This system
      has been proved to be a satisfactory method for the above mentioned wastes.

PMID- 29016268
TI  - Insoluble biodegradative potential of the venice lagoon.
AB  - The sediment phase of the Venice lagoon within an area of shallow water, the
      Palude della Rosa, was studied and three insoluble enzymatic activities
      (cellulase, phosphatase and urease) were found to be linked to the inorganic
      phase. These immobilized enzymes were more resistant to environmental changes,
      even extreme ones, compared to their soluble counterparts. The evolution of their
      activity with pH, temperature and seasonal variation was investigated. While pH
      related activities showed the usual behaviour, the resistance to temperature was
      extremely high and seasonal variation was dependent on immobilization. These
      enzymatic activities could be used as a diagnostic factor for the ecosystem,
      since their presence is related to the nature of the waste products.

PMID- 29016269
TI  - Adsorption of phosphate onto pumice powder.
AB  - The adsorption of phosphate onto pumice powder was studied as a function of time,
      pH and total dissolved phosphate concentration. Phosphate removal efficiency was
      found to be more than 80%. The adsorption reaction was considered to be a
      reversible reaction at which a forward first order reaction is opposed by a
      second order reaction. The reaction rate constant k was calculated as 28.31 +/-
      2.37*10-3. Phosphate adsorption data had a good fit to Freundlich adsorption
      isotherm at pH 3, 5, 7 and 9. In the presence of NaCl, Na2SO4, MgClg, CaCl2, NaF
      and urea, the adsorption was slightly affected.

PMID- 29016270
TI  - Characteristics, quantity and thickening of sludge from a partial lime softening
      plant.
AB  - Water softening using the lime process leads to the production of large
      quantities of sludge. Determining the quantity of sludge produced and its
      dewatering properties is very important in the design, operation and cost of the
      subsequent sludge handling facilities. Presented are the results of a study on
      the partial softening process of a 200 MLD water treatment plant in Edmonton,
      Alberta, Canada. The plant currently softens surface water from a hardness of 180
      mg l-1 as CaCO3 to 110 mg l-1 as CaCO3 in a solid contact clarifier. The sludge
      is gravity thickened prior to centrifugation after which the sludge is hauled off
      site for disposal. Results from the study were used to assess the current
      operation as well as to provide required information for the facilities needs in
      view of a proposed expansion to double the current production. Results from
      measured data indicate that the sludge production can be established by a mass
      balance, chemical (Ca++, Mg++) balance or stoichiometric calculations. Bulk
      density of the lime sludge was correlated to the sludge solids content by a
      quadratic expression. Similarly, the settling velocities at various sludge
      densities were well correlated. The total organic carbon (TOC) content of the
      sludge was found to be unusually high. Analysis of operating records found that
      by maintaining a proper sludge blowdown interval and duration, the sludge
      withdrawal can be optimized for solid contact clarifiers with intermittent sludge
      withdrawal.

PMID- 29016271
TI  - Removal of transition metals from motor oil using ion exchange resins.
AB  - A variety of polystyrene-divinylbenzene resins functionalized with such groups as
      SO3H, N(CH2COOH)2, and SH were tested in the slurry batch mode for the removal of
      transition metals from used motor oil. Naturally occurring materials such as coal
      and clay were also tested. The N(CH2COOH)2 resin (Chelex 100) and the SH resin
      (Duolite GT-73) were found effective removing on the average 70 and 78% of metals
      such as Fe, Pb, Zn, Cu, Ni, and Mn, respectively. About 700 mLs of hot oil when
      pumped through a 37 * 0.9 cm column packed with the Duolite resin could be
      demetalized to the extent of about 80% if the column was first washed with
      hexane.

PMID- 29016272
TI  - Transplanted aquatic mosses and freshwater mussels to investigate the trace metal
      contamination in the rivers Meurthe and Plaine, France.
AB  - Aquatic mosses Cinclidotus nigricans and freshwater mussels Dreissena polymorpha
      were transferred at eight monitoring sites along the rivers Meurthe and Plaine
      (northeastern France) for a biological assessment of the trace metal
      contamination. Autochthonous Fontinalis antipyretica mosses were collected at the
      end of the experiment. The major contaminants detected in the organisms were Cr,
      Ni, Pb and Zn. A comparison between the native and the introduced bryophytes
      showed that the transfer technique was preferable to assess the recent pollution
      situation. In the case of the transplanted mosses, high initial levels of
      strongly bound Pb and Zn prevented an accurate assessment of the contamination
      with these two metals, since only little depuration occurred at unpolluted sites.
      A good qualitative agreement was observed between the indications obtained from
      the mosses and those obtained from the mussels, suggesting that both are suitable
      indicators for monitoring purposes. The observed quantitative disparities were
      attributed to inherent differences in the accumulation strategies of each
      sentinel organism. Due to specific uptake and depuration kinetics, mosses and
      mussels appeared to be complementary in the detection of various types of
      pollution.

PMID- 29016273
TI  - Sorption of lead and thallium on borosilicate glass and polypropylene:
      Implications for analytical chemistry and soil science.
AB  - Adsorption of 10-100 ppb lead and thallium by borosilicate glass and
      polypropylene surfaces was studied. No thallium was adsorbed by either substrate
      at pH 7.0. About 50-60% of the lead was adsorbed by borosilicate glass at pH 5.5
      and pH 7.0, with statistically indistinguishable conditional equilibrium
      constants (KD* values) of 1.47+/-0.40 mL cm-2 and 1.80+/-0.11 mL cm-2,
      respectively. Polypropylene adsorbed significantly more lead than borosilicate
      glass at pH 7.0 (80.9%, KD* =5.33+/-0.45 mL cm-2), and substantially less at pH
      5.5 (16.7%, KD* = 0.27+/-0.03 mL cm-2), indicating a fundamental change in the
      nature of the polypropylene surface. All adsorption data fitted Freundlich plots.
      Preliminary experiments indicate that at pH 5.5, a fraction of the lead
      sequestered by the borosilicate glass may be bound irreversibly by migrating into
      the glass matrix. The results suggest that tectosilicates and silicate glasses
      may represent important adsorbents of some heavy metals in soils, despite showing
      very low intrinsic cation exchange capacities.

PMID- 29016277
TI  - Relational Coping Processes.
AB  - A diagnosis of breast cancer requires a woman to cope with a variety of physical
      and psychosocial challenges that are not faced in isolation. Interpersonal
      relationships are the context for appraisal, development of coping strategies,
      and defining of resources for adaptation to a serious illness. Of particular
      interest is the couple relationship. The level of complexity in understanding the
      process of adaptation is far greater when considering the impact of each
      partner's response on the other partner's coping strategies and the interactive
      management of the emotional recovery. The purpose of this study was to understand
      the specific processes that developed within the partner relationship as the
      couple began the process of recovery. Case-intensive interview data were analyzed
      using an interpretive methodology to construct the dyadic process of the woman
      and her partner. The data analysis revealed two types of processes: one process
      in which the patient's and partner's thoughts, feelings, and emotions were
      acknowledged; the other in which their thoughts, feelings, and emotions were
      moderated or minimized in some way. These patterns were present across couples.

PMID- 29016276
TI  - Hear How I Feel.
AB  - In an effort to heighten the awareness of the high school population, a support
      group program for young people whose parents were diagnosed with cancer received
      funding to produce an educational video titled Hear How I Feel. This article
      reports on the evaluation of the video by 146 high school teachers, guidance
      counselors, and students; elementary school teachers; university undergraduate
      social work students; and health care and social service providers. A qualitative
      analysis of the evaluations indicated that high school teachers and guidance
      counselors were reluctant to use the video in the high school setting because
      they could not respond expertly to emotions that might be elicited. The findings
      suggest that youths desire a forum in which difficult issues can be addressed,
      teachers and guidance counselors need training that would enhance their skill in
      responding to students' emotional responses, and cancer patients and their
      families have psychosocial needs that must be met.

PMID- 29016278
TI  - Racial Differences in the Health of Older-Adult Long-Term Cancer Survivors.
AB  - This article focuses on differences between African-American and White older
      adults who were long-term (five or more years postdiagnosis) survivors of cancer
      regarding reported health problems, symptoms of illness, functional difficulties,
      health worries and concerns, and overall perceptions of health. A conceptual
      model examined the relationship between demographic factors (e.g., race, age,
      cancer- and treatment-related factors) and perceptions of health (e.g., burden of
      disability, health concerns and worries, and self-rated global health).
      Regression analysis examined quantitative data from in-person interviews with 180
      survivors of breast, colorectal, or prostate cancer obtained from the tumor
      registry of the Ireland Cancer Center at University Hospitals Health System of
      Cleveland. African Americans were oversampled to represent 50% of the total
      sample. The analysis indicated that African Americans experienced poorer
      functional health after cancer, even after disease and treatment factors were
      controlled for. However, compared with White survivors, African Americans did not
      report significantly more symptoms attributed to either cancer or its treatment,
      suggesting that their poorer health after cancer may not have been a result of
      either factor but to other comorbid conditions. Moreover, because the
      extensiveness of treatment is a significant predictor of functional disability,
      attention must be paid to the degree to which more extensive treatment among
      African Americans translates into greater disability.

PMID- 29016275
TI  - Effectiveness of Psychoanalytic-Interactional Group Therapy vs. Behavioral Group
      Therapy in Routine Outpatient Treatment of Alcohol-Dependent Patients.
AB  - BACKGROUND: The cognitive behavioral therapy has been extensively investigated to
      assess relapse prevention rates in patients with alcohol dependence. In contrast,
      only little is known regarding the effectiveness of psychoanalytical
      psychotherapy in relapse prevention, although this treatment is widely used and
      especially so in Germany. The aim of this quasi-randomized study was to compare
      the effectiveness of these two group treatments' approaches under the condition
      of routine outpatient treatment in a non-university hospital. METHODS: After
      inpatient detoxification, patients with alcohol dependence were allocated either
      to combined behavioral intervention (CBI) or to psychoanalytic-interactional
      therapy (PIT). The group treatment was carried out weekly over a period of six
      months. Also, the clinical care package included both individual treatment
      sessions (e.g. every 4-6 weeks) and abstinence supporting medication. The main
      outcome criteria included retention rates and frequency of alcohol relapse.
      RESULTS: Some 215 patients (mean age 49.6 years [standard deviation, 10], 56.7%
      males, with a mean duration of alcohol dependence of 16.5 years [range: 1-50
      years]) were included in the study. Overall, CBI clients showed a retention rate
      of 66.7%, compared to 81.8% for PIT clients (p =.008). An intention-to-treat
      analysis of alcohol relapses showed a significant difference between PIT and CBI
      groups (PIT: 33.6%; CBI: 49.5%; p =.018). There were no statistically significant
      differences between the 2 groups in terms of prescription rates of disulfiram,
      naltrexone or acamprosate. CONCLUSIONS: Notwithstanding the study limitations,
      PIT seemed here to be at least as effective as CBI in terms of retention and
      relapse prevention rates' levels.

PMID- 29016279
TI  - Preferences for Psychosocial Interventions Among Newly Diagnosed Cancer Patients
      from a Multiethnic Population.
AB  - This article addresses preferences for psychosocial interventions in newly
      diagnosed cancer patients in a multiethnic sample consisting of Americans of
      European, Filipino, Native Hawaiian, and Japanese ancestry. Patients who were
      diagnosed with cancer four to six months before the study were identified through
      consecutive registrations on the Hawai'i Tumor Registry. Data were collected
      through personal interviews using a standardized questionnaire. Among 194
      patients who participated in the study, 162 (84%) reported experiencing cancer
      related stress. Although few patients had participated in supportive
      interventions, there was considerable interest in these techniques. Most patients
      had received information about diagnosis and treatment, but only 10% had received
      information about psychological counseling. When preferences for supportive
      interventions were linked with demographic characteristics (e.g., gender, age,
      and ethnicity), the most consistent finding was higher levels of interest among
      Filipino patients. Additional research examining ethnic differences in
      preferences for psychosocial support is warranted. Because of the potential for
      greater use of behavioral therapies by patients, educating providers about the
      availability, efficacy, and patients' interest in such interventions is needed.

PMID- 29016280
TI  - Understanding the Barriers to Physical Activity for Cancer Patients.
AB  - For individuals who experience cancer, regular adherence to physical activity has
      been shown to provide benefits ranging from alleviation of symptoms to
      improvements in physical function and quality of life. However, research about
      barriers to participation that compromise adherence and subsequent benefits has
      been identified as needed. The purposes of this article were to (1)
      systematically review the barriers to research and make recommendations, (2)
      consider unique symptoms of disease and treatment regarding their barrier-related
      impact on exercise therapy, and (3) present an organizational framework that will
      aid the investigation and understanding of barriers as they affect adherence to
      prescribed exercise therapy for cancer treatment and recovery.

PMID- 29016274
TI  - Mind the Hype: A Critical Evaluation and Prescriptive Agenda for Research on
      Mindfulness and Meditation.
AB  - During the past two decades, mindfulness meditation has gone from being a fringe
      topic of scientific investigation to being an occasional replacement for
      psychotherapy, tool of corporate well-being, widely implemented educational
      practice, and "key to building more resilient soldiers." Yet the mindfulness
      movement and empirical evidence supporting it have not gone without criticism.
      Misinformation and poor methodology associated with past studies of mindfulness
      may lead public consumers to be harmed, misled, and disappointed. Addressing such
      concerns, the present article discusses the difficulties of defining mindfulness,
      delineates the proper scope of research into mindfulness practices, and
      explicates crucial methodological issues for interpreting results from
      investigations of mindfulness. For doing so, the authors draw on their diverse
      areas of expertise to review the present state of mindfulness research,
      comprehensively summarizing what we do and do not know, while providing a
      prescriptive agenda for contemplative science, with a particular focus on
      assessment, mindfulness training, possible adverse effects, and intersection with
      brain imaging. Our goals are to inform interested scientists, the news media, and
      the public, to minimize harm, curb poor research practices, and staunch the flow
      of misinformation about the benefits, costs, and future prospects of mindfulness
      meditation.

PMID- 29016281
TI  - Assessing the Impact of Leveraging Traditional Leadership on Access to Sanitation
      in Rural Zambia.
AB  - Open defecation is practiced by more than one billion people throughout the world
      and leads to significant public health issues including infectious disease
      transmission and stunted growth in children. Zambia implemented community-led
      total sanitation (CLTS) as an intervention to eliminate open defecation in rural
      areas. To support CLTS and the attainment of open defecation free communities,
      chiefs were considered key agents of change and were empowered to drive CLTS and
      improve sanitation for their chiefdom. Chiefs were provided with data on access
      to sanitation in the chiefdom during chiefdom orientations prior to the
      initiation of CLTS within each community and encouraged to make goals of
      universal sanitation access within the community. Using a survival regression, we
      found that where chiefs were orientated and mobilized in CLTS, the probability
      that a village would achieve 100% coverage of adequate sanitation increased by
      23% (hazard ratio = 1.263, 95% confidence interval = 1.080-1.478, P = 0.003).
      Using an interrupted time series, we found a 30% increase in the number of
      individuals with access to adequate sanitation following chiefdom orientations
      (95% confidence interval = 28.8-32.0%). The mobilization and support of chiefs
      greatly improved the uptake of CLTS, and empowering them with increased CLTS
      knowledge and authority of the program in their chiefdom allowed chiefs to
      closely monitor village sanitation progress and follow-up with their
      headmen/headwomen. These key agents of change are important facilitators of
      public health goals such as the elimination of open defecation in Zambia by 2020.

PMID- 29016282
TI  - Analysis of Health Indicators in Two Rural Communities on the Colombian Caribbean
      Coast: Poor Water Supply and Education Level Are Associated with Water-Related
      Diseases.
AB  - Water-related diseases are closely linked with drinking water, sanitation, and
      hygiene (WASH) indicators, socioeconomic status, education level, or dwelling's
      conditions. Developing countries exhibit a particular vulnerability to these
      diseases, especially rural areas and urban slums. This study assessed
      socioeconomic features, WASH indicators, and water-related diseases in two rural
      areas of the Colombian Caribbean coast. Most of this population did not finish
      basic education (72.3%, N = 159). Only one of the communities had a water supply
      (aqueduct), whereas the other received water via an adapted tanker ship. No
      respondents reported sewage services; 92.7% (N = 204) had garbage service.
      Reported cases of diarrhea were associated with low education levels (P = 2.37 *
      10-9) and an unimproved drinking water supply (P = 0.035). At least one fever
      episode was reported in 20% (N = 44) of dwellings, but the cases were not related
      to any indicator. The Aedes/House index (percentage of houses that tested
      positive for Aedes larvae and/or pupae) was 69%, the container index (percentage
      of water-holding containers positive for Aedes larvae or pupae) 29.4%, and the
      Breteau index (number of positive containers per 100 houses in a specific
      location) was three positive containers per 100 inspected houses. The presence of
      positive containers was associated with the absence of a drinking water supply (P
      = 0.04). The community with poorer health indicators showed greater health
      vulnerability conditions for acquisition of water-related diseases. In summary,
      water supply and educational level were the main factors associated with the
      presence of water-related diseases in both communities.

PMID- 29016283
TI  - Identification of Risk Factors of Multidrug-Resistant Tuberculosis by using
      Classification Tree Method.
AB  - Multidrug-resistant tuberculosis (MDR-TB) has become a major public health
      problem. We tried to apply the classification tree model in building and
      evaluating a risk prediction model for MDR-TB. In this case-control study, 74
      newly diagnosed MDR-TB patients served as the case group, and 95 patients without
      TB from the same medical institution served as the control group. The
      classification tree model was built using Chi-square Automatic Interaction
      Detectormethod and evaluated by income diagram, index map, risk statistic, and
      the area under receiver operating characteristic (ROC) curve. Four explanatory
      variables (history of exposure to TB patients, family with financial
      difficulties, history of other chronic respiratory diseases, and history of
      smoking) were included in the prediction model. The risk statistic of
      misclassification probability of the model was 0.160, and the area under ROC
      curve was 0.838 (P < 0.01). These suggest that the classification tree model
      works well for predicting MDR-TB. Classification tree model can not only predict
      the risk of MDR-TB effectively but also can reveal the interactions among
      variables.

PMID- 29016284
TI  - Is Visceral Leishmaniasis Different in Immunocompromised Patients Without Human
      Immunodeficiency Virus? A Comparative, Multicenter Retrospective Cohort Analysis.
AB  - Although visceral leishmaniasis (VL) can affect immunocompromised patients, data
      from the human immunodeficiency virus (HIV) infection context are limited, and
      the characteristics of VL in other immunosuppression scenarios are not well
      defined. A retrospective review of all cases of VL in immunocompromised patients
      from January 1997 to December 2014 in two Spanish hospitals on the Mediterranean
      coast was performed. We included 18 transplant recipients (kidney: 7, liver: 4,
      lung: 3, heart: 2, and blood marrow: 2), 12 patients with other causes of
      immunosuppression (myasthenia gravis: 3 and rheumatoid arthritis: 2), and 73 VL
      HIV-positive patients. Fever was more common in transplant patients (94.4%) and
      patients with other types of immunosuppression (100%) than in HIV-positive
      individuals (73.3%). Hepatomegaly was less common in transplant recipients
      (27.8%) and patients with other types of immunosuppression (41.7%) compared with
      HIV-positive patients (69.9%) (P = 0.01; P = 0.001, respectively). Patients with
      other types of immunosuppression had a median leukocyte count of 1.5 * 109/L,
      significantly lower than HIV-positive patients (2.5 * 109/L) (P = 0.04). Serology
      was more commonly positive in nontransplant immunosuppressed individuals (75%)
      and transplant recipients (78.6%) than in HIV-patients (13.8%) (P < 0.001).
      Antimonial therapy was rarely used in transplant recipients (1.9%) and never in
      patients with other immunosuppressive conditions, whereas 34.2% of HIV-positive
      patients received it (P = 0.05 and P = 0.01, respectively). Mortality was 16.7%
      in both transplant recipients and patients with other immunosuppressive
      conditions and 15.1% in HIV-positive patients. The features of VL may be
      different in immunosuppressed patients, with more fever and less hepatomegaly and
      leukopenia than in HIV-infected patients.

PMID- 29016285
TI  - Development and Evaluation of a Loop-Mediated Isothermal Amplification Assay for
      the Detection of Treponema pallidum DNA in the Peripheral Blood of Secondary
      Syphilis Patients.
AB  - Secondary syphilis (SS) has always been puzzling for the clinicians because of
      the similarity of the appearance of skin rashes with other dermatoses.
      Serological assays are useful, but less sensitive at an early stage of SS or when
      patients are immunodeficient. Therefore, there is an urgent need to develop a
      rapid and effective tool for the diagnosis of SS, which may play an important
      role in the control of epidemic syphilis outbreaks. In this study, we evaluated a
      loop-mediated isothermal amplification (LAMP) assay, targeting gene encoding the
      basic membrane protein of Treponema pallidum, to detect the presence of
      circulating T. pallidum DNA in the blood of SS patients. The specificity of LAMP
      was validated using three strains of Spirochaetales and six common clinical
      bacteria. The clinical applicability of LAMP assay was assessed using 642 blood
      samples from clinically suspected SS patients and 80 samples from healthy blood
      donors, showing a sensitivity of 82.1% and a specificity of 100.0% in the
      diagnosis of SS. Thus, our results indicate that the LAMP can be used as a
      supplementary method for the diagnosis of SS.

PMID- 29016286
TI  - Chagas Disease Infection among Migrants at the Mexico/Guatemala Border.
AB  - Chagas disease results in the largest burden, in terms of disability-adjusted
      life-years, of any parasitic disease in the Americas. Monitoring Chagas disease
      among migrants is critical to controlling its spread and to serving the needs of
      the migrant community. Therefore, we determined the prevalence and correlates of
      Chagas disease in regional and international migrant populations at the
      Mexico/Guatemala border. Data were collected as part of a larger study of human
      immunodeficiency virus (HIV) and migration. Participants were a sample of recent
      regional and international migrants who used an illicit substance or had recent
      problem drinking. Trypanosoma cruzi infection was classified as testing positive
      on two different enzyme-linked immunosorbent assays (ELISAs). Interviewer
      administered surveys captured sociodemographics, migration history, Chagas
      disease knowledge, and access to care. We enrolled 389 recent migrants, and the
      prevalence of Chagas disease was 3.1%. Only 19% of the participants reported
      having ever heard of the disease and less than 1% had been previously tested.
      Trypanosoma cruzi-positive participants were more likely to have been born in a
      rural area or town than a city (92% yes versus 59% no, P = 0.02) and have
      recently lived in a house with a makeshift roof (33% yes versus 8% no, P < 0.01),
      walls (42% yes versus 13% no, P < 0.01), or floor (50% yes versus 21% no, P <
      0.02), or cinderblock walls (92% yes versus 63% no, P = 0.04). With migration
      rapidly changing the distribution of Chagas disease, more work needs to be done
      to create targeted surveillance programs and provide access to affordable
      treatment among Latin American migrants.

PMID- 29016287
TI  - Benznidazole Nanoformulates: A Chance to Improve Therapeutics for Chagas Disease.
AB  - This article describes the characterization of various encapsulated formulations
      of benznidazole, the current first-line drug for the treatment of Chagas disease.
      Given the adverse effects of benznidazole, safer formulations of this drug have a
      great interest. In fact, treatment of Chagas disease with benznidazole has to be
      discontinued in as much as 20% of cases due to side effects. Furthermore,
      modification of delivery and formulations could have potential effects on the
      emergence of drug resistance. The trypanocidal activity of new nanostructured
      formulations of benznidazole to eliminate Trypanosoma cruzi was studied in vitro
      as well as their toxicity in two cultured mammalian cell lines (HepG2 and
      Fibroblasts). Nanoparticles tested included nanostructured lipid carriers, solid
      lipid nanoparticles, liposomes, quatsomes, and cyclodextrins. The in vitro
      cytotoxicity of cyclodextrins-benznidazole complexes was significantly lower than
      that of free benznidazole, whereas their trypanocidal activity was not hampered.
      These results suggest that nanostructured particles may offer improved
      therapeutics for Chagas disease.

PMID- 29016288
TI  - Efficacy and Safety of Liposomal Amphotericin B for Visceral Leishmaniasis in
      Children and Adolescents at a Tertiary Care Center in Bihar, India.
AB  - Liposomal amphotericin B is being used increasingly to reduce the burden of kala
      azar from the Indian subcontinent. There are studies which have evaluated
      efficacy and safety of liposomal amphotericin B for visceral leishmaniasis in all
      age groups. However, the only study that specifically addressed treatment of
      childhood visceral leishmaniasis did not include all ages or document renal and
      liver function. We, therefore, felt it was important to reassess the efficacy and
      safety of single dose liposomal amphotericin B in children and adolescents. A
      total of 100 parasitologically confirmed visceral leishmaniasis patients aged <
      15 years were included in this study. Participants consisted of 65 males and 35
      females. All of them had come from the endemic region of Bihar. They were
      administered one dose intravenous infusion of liposomal amphptericin B at 10
      mg/kg body weight. Efficacy was assessed as initial and final cure at 1 and 6
      months, respectively, and safety of all participants who were recruited in the
      study. The initial and final cure rate by per protocol analysis was 100% and
      97.9%, respectively. Chills and rigors were the most commonly occurring adverse
      events (AEs). All the AEs were mild in intensity, and none of the patients
      experienced any serious AEs. No patients developed nephrotoxicity. Our finding
      indicates that liposomal amphotericin B at 10 mg/kg body weight is safe and
      effective in children. Results of our study support the use of single dose
      liposomal amphotericin B in all age group populations for elimination of kala
      azar from the Indian subcontinent.

PMID- 29016290
TI  - Variability of Cutaneous Leishmaniasis Lesions Is Not Associated with Genetic
      Diversity of Leishmania tropica in Khyber Pakhtunkhwa Province of Pakistan.
AB  - Leishmania tropica is the causative agent of cutaneous leishmaniasis in Pakistan.
      Here, intraspecific diversity of L. tropica from northern Pakistan was
      investigated using multilocus microsatellite typing. Fourteen polymorphic
      microsatellite markers were typed in 34 recently collected L. tropica isolates
      from Pakistan along with 158 archival strains of diverse Afro-Eurasian origins.
      Previously published profiles for 145 strains of L. tropica originating from
      different regions of Africa, Central Asia, Iran, and Middle East were included
      for comparison. Six consistently well-supported genetic groups were resolved: 1)
      Asia, 2) Morroco A, 3) Namibia and Kenya A, 4) Kenya B/Tunisia and Galilee, 5)
      Morocco B, and 6) Middle East. Strains from northern Pakistan were assigned to
      Asian cluster except for three that were placed in a geographically distant
      genetic group; Morocco A. Lesion variability among these Pakistani strains was
      not associated with specific L. tropica genetic profile. Pakistani strains showed
      little genetic differentiation from strains of Iraq, Afghanistan, and Syria (FST
      = 0.00-0.06); displayed evidence of modest genetic flow with India (FST = 0.14).
      Furthermore, genetic structuring within these isolates was not geographically
      defined. Pak-Afghan cluster was in significant linkage disequilibrium (IA =
      1.43), had low genetic diversity, and displayed comparatively higher
      heterozygosity (FIS = -0.62). Patterns of genetic diversity observed suggest
      dominance of a minimally diverse clonal lineage within northern Pakistan. This is
      surprising as a wide clinical spectrum was observed in patients, suggesting the
      importance of host and other factors. Further genotyping studies of L. tropica
      isolates displaying different clinical phenotypes are required to validate this
      potentially important observation.

PMID- 29016292
TI  - Risk Factors for Methicillin-Resistant Staphylococcus aureus Carriage among
      Patients at Admission to the Surgical Ward in a Resource-Limited Hospital in
      Indonesia.
AB  - This study aimed to identify risk factors for methicillin-resistant
      Staphylococcus aureus (MRSA) carriage among patients at admission to the surgery
      ward in a resource-limited hospital in Indonesia. A case-control study was
      performed including 65 MRSA carriage patients and 132 non-MRSA carriage patients
      screened at admission to surgery wards in a hospital in Malang, East Java. For
      MRSA screening, swabs were obtained from nares and throat, cultured in an
      enrichment broth followed by subculturing onto CHROMagarTM MRSA; suspected
      colonies were confirmed by polymerase chain reaction. Patients referred from
      other hospitals, patients transferred from the surgical acute care unit, patients
      that had a surgical procedure within 3 months before admission, and
      immunocompromised patients were more likely to be MRSA carriers at admission to
      the surgery wards. Selective MRSA screening of patients according to such risk
      factors at admission would efficiently detect MRSA carriers and may help control
      MRSA dissemination in surgery wards in limited-resource settings.

PMID- 29016291
TI  - Chikungunya Detection during Dengue Outbreak in Sumatra, Indonesia: Clinical
      Manifestations and Virological Profile.
AB  - Chikungunya fever (CHIK) is an acute viral infection caused by infection with
      chikungunya virus (CHIKV). The disease affects people in areas where certain
      Aedes species mosquito vectors are present, especially in tropical and
      subtropical countries. Indonesia has witnessed CHIK disease since the early 1970s
      with sporadic outbreaks occurring throughout the year. The CHIK clinical
      manifestation, characterized by fever, headache, and joint pain, is similar to
      that of dengue (DEN) disease. During a molecular study of a DEN outbreak in
      Jambi, Sumatra, in early 2015, DENV-negative samples were evaluated for evidence
      of CHIKV infection. Among 103 DENV-negative samples, eight samples were confirmed
      (7.8%) as positive for CHIKV by both molecular detection and virus isolation. The
      mean age of the CHIK patients was 21.3 +/- 9.1 (range 11-35 years). The clinical
      manifestations of the CHIK patients were mild and mimicked DEN, with fever and
      headache as the main symptoms. Only three out of eight patients presented with
      classical joint pain. Sequencing of the envelope glycoprotein E1 gene and
      phylogenetic analysis identified all CHIKV isolates as belonging to the Asian
      genotype. Overall, our study confirms sustained endemic CHIKV transmission and
      the presence of multiple arboviruses circulating during a DEN outbreak in
      Indonesia. The co-circulation of arboviruses poses a public health threat and is
      likely to cause misdiagnosis and underreporting of CHIK in DEN-endemic areas such
      as Indonesia.

PMID- 29016294
TI  - Environmental Enteric Dysfunction: A Case Definition for Intervention Trials.

PMID- 29016295
TI  - Ignoring the "Itch": The Global Health Problem of Scabies.
AB  - Infestation with Sarcoptes scabiei var. hominis is a common human parasitic
      affliction endemic in tropical developing countries. Scabies is transmitted by
      close person-person contact, and outbreaks have been reported in reception
      centers for asylum seekers. Scabies presents clinically as extremely pruritic
      excoriated papules and linear burrows in the skin. This infestation predisposes
      to bacterial skin infections that can result in serious complications affecting
      the kidneys and possibly the heart. Treatment of individuals with scabies and
      their close contacts involves the use of antiparasitic agents. First-line
      treatment is topical 5% permethrin cream. Community mass drug administration,
      followed by active case finding with targeted treatment, is a promising approach
      that can reduce the prevalence of both scabies and bacterial skin infections.
      Organizations such as the International Alliance for the Control of Scabies are
      advocating for the development of integrated disease control strategies in an
      effort to decrease scabies infestation worldwide.

PMID- 29016293
TI  - Molecular and Phenotypic Characterization of Diarrheagenic Escherichia coli
      Strains Isolated from Bacteremic Children.
AB  - Escherichia coli is an important cause of Gram-negative bacteremia. The aim of
      this study was to characterize at the molecular and phenotypic levels E. coli
      strains belonging to different diarrheagenic pathotypes [diarrheagenic E. coli
      (DEC)] isolated from bacteremia in children younger than 5 years of age. Seventy
      bacteremia E. coli strains were collected in a prospective study in 12 hospitals
      in Lima, Peru. The presence of virulence genes associated with DEC
      [enterotoxigenic (lt and st), enteropathogenic (eaeA), shiga toxin-producing
      (stx1and stx2), enteroinvasive (ipaH), enteroaggregative (aggR), and diffusely
      adherent (daaD)] was determined by multiplex real-time polymerase chain reaction
      (PCR). Those positive E. coli strains were further analyzed for 18 additional
      virulence factors encoding genes and others phenotypic features. Virulence genes
      associated with DEC were identified in seven bacteremic children (10%),
      including: one aggR-positive [enteroaggregative E. coli (EAEC)], one eaeA
      positive [enteropathogenic E. coli (EPEC)], one st-positive [enterotoxigenic E.
      coli (ETEC)], one daaD-positive [diffusely adherent E. coli (DAEC)], and three
      strain positive for aggR and daaD (EAEC/DAEC) at the same time. All strains,
      except EPEC, had the Ag43 adhesin, and all, except ETEC had the siderophore gene
      fyuA. The phylogenetic profile of these strains was variable, two (B2), two (D),
      two (A), and one (B1) strain. These isolates were susceptible to all tested
      antibacterial agents except to ampicillin and gentamicin. The three EAEC/DAEC
      strains showed biofilm formation and aggregative adhesion and had the same
      repetitive extragenic palindromic-PCR patterns. These findings suggest that some
      DEC strains, especially agg-R and daa-D positive, might cause bacteremia in
      children.

PMID- 29016289
TI  - Experimental and Clinical Treatment of Chagas Disease: A Review.
AB  - Chagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi that
      infects a broad range of triatomines and mammalian species, including man. It
      afflicts 8 million people in Latin America, and its incidence is increasing in
      nonendemic countries owing to rising international immigration and nonvectorial
      transmission routes such as blood donation. Since the 1960s, the only drugs
      available for the clinical treatment of this infection have been benznidazole
      (BZ) and nifurtimox (NFX). Treatment with these trypanocidal drugs is recommended
      in both the acute and chronic phases of CD. These drugs have low cure rates
      mainly during the chronic phase, in addition both drugs present side effects that
      may result in the interruption of the treatment. Thus, more efficient and better
      tolerated new drugs or pharmaceutical formulations containing BZ or NFX are
      urgently needed. Here, we review the drugs currently used for CD chemotherapy,
      ongoing clinical assays, and most-promising new experimental drugs. In addition,
      the mechanism of action of the commercially available drugs, NFX and BZ, the
      biodistribution of the latter, and the potential for novel formulations of BZ
      based on nanotechnology are discussed. Taken together, the literature emphasizes
      the urgent need for new therapies for acute and chronic CD.

PMID- 29016297
TI  - Case Series of Naegleria fowleri Primary Ameobic Meningoencephalitis from
      Karachi, Pakistan.
AB  - Naegleria fowleri causes primary amoebic meningoencephalitis (PAM) which is
      almost always fatal. Naegleria fowleri is waterborne, and its infections are
      usually associated with aquatic activities but it can also be transmitted via the
      domestic water supply. An increasing number of N. fowleri cases have been
      reported from Pakistan. Improved methods for diagnosis are required. We report
      the utility of polymerase chain reaction (PCR) for the diagnosis of N. fowleri in
      patients suspected of PAM. One hundred and sixteen cases suspected of having PAM
      were examined. Cerebrospinal fluid (CSF) specimens were tested at the Aga Khan
      University Hospital, Karachi. Nineteen CSF specimens were positive for N. fowleri
      using PCR. Naegleria fowleri positive patients had a median age of 28 years and
      were 84% male and 16% female. Overall, CSF wet preparation microscopy was
      performed in 85 (73%) cases and identified that seven specimens were positive for
      motile trophozoites. The CSF wet preparation results were available for 15 of the
      19 N. fowleri PCR positive CSF samples; seven (40%) wet preparations were
      positive. Our data highlight the threat of N. fowleri infection as a cause of
      PAM. It also emphasizes the utility of the PCR-based diagnosis of the amoeba for
      early diagnosis and management of the disease.

PMID- 29016296
TI  - Strategies to Improve Management of Acute Watery Diarrhea during a Military
      Deployment: A Cost Effectiveness Analysis.
AB  - To inform policy and decision makers, a cost-effectiveness model was developed to
      predict the cost-effectiveness of implementing two hypothetical management
      strategies separately and concurrently on the mitigation of deployment-associated
      travelers' diarrhea (TD) burden. The first management strategy aimed to increase
      the likelihood that a deployed service member with TD will seek medical care
      earlier in the disease course compared with current patterns; the second strategy
      aimed to optimize provider treatment practices through the implementation of a
      Department of Defense Clinical Practice Guideline. Outcome measures selected to
      compare management strategies were duty days lost averted (DDL-averted) and a
      cost effectiveness ratio (CER) of cost per DDL-averted (USD/DDL-averted).
      Increasing health care and by seeking it more often and earlier in the disease
      course as a stand-alone management strategy produced more DDL (worse) than the
      base case (up to 8,898 DDL-gained per year) at an increased cost to the
      Department of Defense (CER $193). Increasing provider use of an optimal evidence
      based treatment algorithm through Clinical Practice Guidelines prevented 5,299
      DDL per year with overall cost savings (CER -$74). A combination of both
      strategies produced the greatest gain in DDL-averted (6,887) with a modest cost
      increase (CER $118). The application of this model demonstrates that changes in
      TD management during deployment can be implemented to reduce DDL with likely
      favorable impacts on mission capability and individual health readiness. The
      hypothetical combination strategy evaluated prevents the most DDL compared with
      current practice and is associated with a modest cost increase.

PMID- 29016298
TI  - Case Report: Cysticercosis: Sonographic Diagnosis of a Treatable Cause of
      Epilepsy and Skin Nodules.
AB  - A case of disseminated cysticercosis of brain, muscle subcutaneous tissue is
      reported and the use of musculoskeletal ultrasound in the diagnosis of the
      condition emphasized.

PMID- 29016300
TI  - Relative Bradycardia in Scrub Typhus.
AB  - To investigate the relationship between heart rate and temperature, we examined
      493 febrile patients with documented disease. These patients were diagnosed
      serologically and analyzed retrospectively: 337 (68.4%) responded to fever with
      increased heart rate < 10 beats/minute/ degrees C (relative bradycardia [RB]),
      and 156 patients had a heart rate response >= 10 beats/minute/ degrees C (general
      heart rate increase [GHRI]). The RB group had a higher median resting heart rate
      and lower heart rate at maximum temperature than the GHRI group. Despite
      differences in heart rate response, no significant differences were seen in
      clinical outcomes (acute kidney injury, systemic inflammatory response syndrome
      (SIRS), and death). We concluded that most patients with scrub typhus presented
      with RB. In scrub typhus infection, RB can be included as one of the clinical
      features for differential diagnosis from other infectious diseases.

PMID- 29016299
TI  - Detection of Mycoplasma pneumoniae and Legionella pneumophila in Patients Having
      Community-Acquired Pneumonia: A Multicentric Study from New Delhi, India.
AB  - Atypical pathogens including Mycoplasma pneumoniae and Legionella pneumophila are
      increasingly recognized as important causes of community-acquired pneumonia
      (CAP). Mycoplasma pneumoniae accounts for 20-40% of all CAP and L. pneumophila is
      responsible for 3-15% of cases. The paucity of data from India in this regard
      prompted us to conduct this prospective multicentric analysis to detect the
      prevalence of M. pneumoniae and L. pneumophila in our geographical region. A
      total of 453 patients with symptoms of pneumonia and 90 controls with no history
      of lower respiratory tract infections were included in the study. A duplex
      polymerase chain reaction (PCR) targeting 543 bp region of P1 adhesin gene of M.
      pneumoniae and 375 bp region of macrophage infectivity potentiator (mip) gene of
      L. pneumophila was standardized for simultaneous detection of these atypical
      pathogens. Respiratory secretions, blood, and urine samples were collected from
      each patient and control and were subjected to duplex PCR, culture and serology
      for M. pneumoniae and L. pneumophila. Urine samples were subjected for detecting
      L. pneumophila antigen. Among the 453 patients investigated for M. pneumoniae, 52
      (11.4%) were positive for IgM antibodies, 17 were positive by culture, and seven
      tested positive by PCR (P1 gene). Similarly for L. pneumophila, 50 cases (11%)
      were serologically positive for IgM antibodies, one was positive by PCR (mip
      gene) and urine antigen detection. A total of eight samples were positive by
      duplex PCR for M. pneumoniae P1 gene (N = 7) and L. pneumophila mip gene (N = 1).
      Of the 90 controls, two samples (2.2%) showed IgM positivity, and 15 (16.7%)
      showed IgG positivity for M. pneumoniae. For L. pneumophila, three samples (3.3%)
      tested positive for IgM, and 12 (13.3%) tested positive for IgG antibodies. The
      study findings indicate the presence of M. pneumoniae and L. pneumophila in our
      geographical region, and a combination of laboratory approaches including PCR,
      culture, and serology is required for effective detection of these agents.

PMID- 29016301
TI  - Case Report: Primary Tuberculosis of the Bilateral Breast.
AB  - Primary breast tuberculosis is rare. We report a case of bilateral primary breast
      tuberculosis. The patient received incisional drainage and debridement of both
      breasts. Histopathology of the breast tissues revealed chronic granulomatous
      inflammation and positive acid-fast stain. The patient received antitubercular
      therapy for 18 months, and she achieved complete resolution.

PMID- 29016302
TI  - Diagnosis of Louse-Borne Relapsing Fever despite Negative Microscopy in Two
      Asylum Seekers from Eastern Africa.
AB  - We report two cases of louse-borne relapsing fever observed at our Institution in
      June 2016. Both patients were young asylum seekers from Africa who had recently
      arrived in Milan, Italy. Notably, direct microscopic examination of peripheral
      blood smears was repeatedly negative for the presence of spirochetes and the
      diagnosis, supported by clinical and epidemiologic evidence, required molecular
      confirmation by polymerase chain reaction amplification of DNA extracted from
      blood and sequencing of the amplified products.

PMID- 29016303
TI  - Undiagnosed Active Pulmonary Tuberculosis among Pilgrims during the 2015 Hajj
      Mass Gathering: A Prospective Cross-sectional Study.
AB  - Mass gatherings pose a risk for tuberculosis (TB) transmission and reactivation
      of latent TB infection. The annual Hajj pilgrimage attracts 2 million pilgrims
      many from high TB-endemic countries. We evaluated the burden of undiagnosed
      active pulmonary TB in pilgrims attending the 2015 Hajj mass gathering. We
      conducted a prospective cross-sectional study in Mecca, Kingdom of Saudi Arabia,
      for nonhospitalized adult pilgrims from five high TB-endemic countries.
      Enrollment criteria were the presence of a cough and the ability to produce a
      sputum sample. Sputum samples were processed using the Xpert MTB-RIF assay. Data
      were analyzed for drug-resistant TB, risk factors, and comorbidities by the
      country of origin. Of 1,164 consenting pilgrims enrolled from five countries:
      Afghanistan (316), Bangladesh (222), Nigeria (176), Pakistan (302), and South
      Africa (148), laboratory results were available for 1,063 (91.3%). The mean age
      of pilgrims was 54.5 (range = 18-94 years) with a male to female ratio of 2.6:1;
      27.7% had an underlying comorbidity, with hypertension and diabetes being the
      most common, 20% were smokers, and 2.8% gave a history of previous TB treatment.
      Fifteen pilgrims (1.4%) had active previously undiagnosed drug-sensitive
      pulmonary TB (Afghanistan [12; 80%], Pakistan [2; 13.3%], and Nigeria [1; 6.7%]).
      No multidrug-resistant TB cases were detected. Pilgrims from high TB-endemic
      Asian and African countries with undiagnosed active pulmonary TB pose a risk to
      other pilgrims from over 180 countries. Further studies are required to define
      the scale of the TB problem during the Hajj mass gathering and the development of
      proactive screening, treatment and prevention guidelines.

PMID- 29016305
TI  - Real-Time Polymerase Chain Reaction Assay on Bronchoalveolar Lavage: An
      Alternative Method for Diagnosing Chronic Pulmonary Schistosomiasis?
AB  - Schistosomiasis causes mainly hepatic and genitourinary damage. Although lung
      nodules have been commonly described in acute phase, they are presumably
      underdiagnosed in chronic schistosomiasis. We previously reported a series of
      patients with chronic pulmonary schistosomiasis confirmed by the histological
      examination of the lung biopsies. In the present work, we retrospectively tested
      an in-house real-time polymerase chain reaction for Schistosoma (currently
      validated for diagnosis on stool and on urine) in the bronchoalveolar lavage
      (BAL) of a couple of those patients, and both resulted positive. The possibility
      of testing BAL with molecular methods targeting a wide spectrum of pathogens,
      including parasites, is appealing. Further studies are needed to validate this
      technique that might reduce unnecessary biopsies.

PMID- 29016306
TI  - Case Report: Bullous Scabies in Two Children below 10 Years.
AB  - Bullous scabies is an infrequent and atypical presentation of scabies, with
      predilection for elderly and males. Its median age of presentation is 70 years.
      We report two male cases of bullous scabies who were 7 years and 6 months old.
      Both patients had excellent response to sulfur 10% ointment alone and have had no
      recurrence in more than 3 months of follow-up.

PMID- 29016308
TI  - Absence of Loa loa Microfilaremia among Newly Arrived Congolese Refugees in
      Texas.
AB  - The Centers for Disease Control and Prevention recommends that refugees at risk
      of Loa loa infection be tested for microfilaria before treatment with ivermectin.
      We report observational results of this approach in African refugees in Texas.
      Daytime blood smears were performed for microfilaria on at-risk African refugees
      who arrived in Texas from July 1, 2014 through December 30, 2016. Clinics were
      asked if there were any adverse events reported among those who received
      ivermectin. Of the 422 persons screened, 346 (82%) were born in L. loa-endemic
      countries, with 332 (96%) of these being born in the Democratic Republic of
      Congo. No smears detected microfilaria, and all received presumptive ivermectin
      with no reports of significant adverse events. In this investigation, the
      prevalence of significant microfilarial load in sub-Saharan African refugees
      appeared to be low, and ivermectin treatment was safe and well tolerated.

PMID- 29016307
TI  - The Differential Expression and Possible Function of Long Noncoding RNAs in Liver
      Cells Infected by Dengue Virus.
AB  - The function of long noncoding RNAs (lncRNAs) in liver injury resulted by dengue
      virus (DENV) infection have not yet been explored. The differential expression
      profiles of lncRNAs (as well as mRNAs) in the L-02 liver cells infected by DENV1,
      DENV2, or uninfected were compared and analyzed after a high throughput RNA seq.
      The significantly up-regulated and down-regulated lncRNAs (or mRNAs) resulted by
      DENV infection were identified with a cutoff value at log2 (ratio) >= 1.5 and
      log2 (ratio) <= -1.5 (ratio = the reads of the lncRNAs or mRNAs from the
      infection groups divided by the reads from the control group). Several
      differentially expressed lncRNAs were verified with reverse transcription
      quantitative real-time polymerase chain reaction (RT-qPCR). Target gene analysis,
      pre-miRNA prediction, and the lncRNA-mRNA co-expression network construction were
      performed to predict the function of the differentially expressed lncRNAs. The
      differentially expressed lncRNAs were associated with biosynthesis, DNA/RNA
      related processes, inhibition of estrogen signaling pathway, sterol biosynthetic
      process, protein dimerization activity, vesicular fraction in DENV1 infection
      group; and with protein secretion, methyltransferase process, host cell
      cytoskeleton reorganization and the small GTPase Ras superfamily, inhibition of
      cell proliferation, induction of apoptosis in DENV2 infection. LncRNAs might be
      novel diagnostic markers and targets for further researches on dengue infection
      and liver injury resulted by dengue virus.

PMID- 29016310
TI  - Case Report: A Cluster of Three Leptospirosis Cases in a New York City Abattoir
      and an Unusual Complication in the Index Case.
AB  - We report the case of a 46-year-old male abattoir worker who developed myalgias,
      shortness of breath, and irritability 2 weeks after sustaining a laceration to
      the hand with a knife at work. During his hospital evaluation for septic shock he
      was noted to be febrile, hypotensive, profoundly jaundiced with aseptic
      meningitis, and renal failure, and was diagnosed with Leptospirosis interrogans
      infection confirmed by serum and urine polymerase chain reaction. After standard
      antibiotic therapy and recovery from severe clinical illness, he developed
      unilateral orchitis with pyuria secondary to leptospirosis, a well-established
      complication in the veterinary literature, but of which we offer the first report
      in humans in the English literature. The case presented was also the index case
      that uncovered a cluster outbreak of leptospirosis in New York City during the
      winter of 2016-2017, involving a total of three patients who lived or worked
      within a block of the abattoir. Two patients survived whereas the third died of
      pulmonary hemorrhage shortly after seeking medical care.

PMID- 29016304
TI  - Hair Mercury Level is Associated with Anemia and Micronutrient Status in Children
      Living Near Artisanal and Small-Scale Gold Mining in the Peruvian Amazon.
AB  - Anemia has been widely studied in global health contexts because of severe
      nutritional deficiency, and more recently, inflammatory status, but chemical
      exposures are rarely considered. Until recently, "anemia" was used synonymously
      with "iron deficiency anemia (IDA)" in global health settings. However, only 50%
      of anemia cases worldwide are IDA. Environmental toxicology studies of anemia
      risk have generally focused on populations in developed countries, albeit with
      high exposure to environmental toxicants, such as lead or cadmium. In the
      developing world, toxicant exposures commonly coexist with other risk factors for
      anemia. In particular, artisanal and small-scale gold mining (ASGM) communities
      are at risk for dietary methylmercury exposure through contaminated fish
      consumption, and for anemia due to food insecurity and infectious and chronic
      diseases. Here, we report analysis of total hair mercury content, hemoglobin, and
      serum micronutrient levels in children < 12 years of age (N = 83) near ASGM in
      the Peruvian Amazon. Forty-nine percent (N = 29/59) of those aged < 5 years were
      anemic (< 11 g/dL) and 52% (N = 12/23) of those aged 5-11 years (< 11.5 g/dL).
      Few children were stunted, wasted, or micronutrient deficient. Median total hair
      mercury was 1.18 MUg/g (range: 0.06-9.70 MUg/g). We found an inverse association
      between total mercury and hemoglobin (beta = -0.12 g/dL, P = 0.06) that persisted
      (beta = -0.14 g/dL, P = 0.04) after adjusting for age, sex, anthropometrics, and
      vitamin B12 in multivariate regression. This study provides preliminary evidence
      that methylmercury exposure is associated with anemia, which is especially
      relevant to children living near ASGM.

PMID- 29016309
TI  - Comparative Prevalence of Plasmodium falciparum Resistance-Associated Genetic
      Polymorphisms in Parasites Infecting Humans and Mosquitoes in Uganda.
AB  - Controlling malaria in high transmission areas, such as much of sub-Saharan
      Africa, will require concerted efforts to slow the spread of drug resistance and
      to impede malaria transmission. Understanding the fitness costs associated with
      the development of drug resistance, particularly within the context of
      transmission, can help guide policy decisions to accomplish these goals, as
      fitness constraints might lead to decreased transmission of drug-resistant
      strains. To determine if Plasmodium falciparum resistance-mediating polymorphisms
      impact on development at different parasite stages, we compared the genotypes of
      parasites infecting humans and mosquitoes from households in Uganda. Genotypes at
      14 polymorphic loci in genes encoding putative transporters (pfcrt and pfmdr1)
      and folate pathway enzymes (pfdhfr and pfdhps) were characterized using ligase
      detection reaction-fluorescent microsphere assays. In paired analysis using the
      Wilcoxon signed-rank test, prevalences of mutations at 12 loci did not differ
      significantly between parasites infecting humans and mosquitoes. However,
      compared with parasites infecting humans, those infecting mosquitoes were
      enriched for the pfmdr1 86Y mutant allele (P = 0.0001) and those infecting
      Anopheles gambiae s.s. were enriched for the pfmdr1 86Y (P = 0.0001) and pfcrt
      76T (P = 0.0412) mutant alleles. Our results suggest modest directional selection
      resulting from varied fitness costs during the P. falciparum life cycle. Better
      appreciation of the fitness implications of drug resistance mediating mutations
      can inform optimal malaria treatment and prevention strategies.

PMID- 29016311
TI  - Case Report: Severe Imported Influenza Infections Developed during Travel in
      Reunion Island.
AB  - We report two cases of severe influenza infection imported by tourist patients
      from their country of origin and developed during travel. While studies have
      reported cases of influenza infections acquired during travel, here we examine
      two cases of severe influenza infection contracted in the country of origin that
      led to diagnosis and therapeutic problems in the destination country. No
      international recommendation exists concerning influenza vaccination before
      travel, and few countries recommend it for all travelers. Our study suggests that
      travel should be canceled when infectious signs are observed before departure.
      Influenza is a very common infection that is often benign, but sometimes very
      severe. The most severe cases include shock, acute respiratory distress syndrome
      (ARDS), myocarditis, rhabdomyolysis, and multiple organ failure. Management can
      require exceptional therapies, such as extracorporeal membrane oxygenation. A
      number of studies have focused on influenza infection in travelers. Cases of
      influenza acquired during travel have been reported in this literature, but no
      study has examined cases of influenza imported from the country of origin and
      developed while abroad. The latter situation may lead to 1) diagnostic problems
      during the nonepidemic season or in places where diagnostic techniques are
      lacking and 2) therapeutic difficulties resulting from the unavailability of
      techniques for the management of severe influenza infection in tourist areas.
      Here, we report two cases of extremely severe influenza infection imported by
      tourists from their country of origin and developed during travel.

PMID- 29016312
TI  - Dengue Virus Serotype 2 Established in Northern Mozambique (2015-2016).
AB  - After the report of an outbreak of dengue virus serotype 2 in 2014 in Nampula and
      Pemba cities, northern Mozambique, a surveillance system was established by the
      National Institute of Health. A study was performed during 2015-2016 to monitor
      the trend of the outbreak and confirm the circulating serotype of dengue virus
      (DENV). After the inclusion of consenting patients who met the case definition,
      samples from 192 patients were tested for the presence of nonstructural protein 1
      antigen, and 60/192 (31%) samples were positive. Further analysis included DENV
      IgM antibodies, with 39 (20%) IgM positive cases. Reverse transcriptase (RT) PCR
      was performed for identification of the prevailing DENV serotype; 21/23 tested
      samples were DENV-2 positive, with DENV-2 present in both affected cities. When
      sequencing DENV, phenotype Cosmopolitan was identified. The surveillance
      indicates ongoing spread of DENV-2 in northern Mozambique 2 years after the first
      report of the outbreak.

PMID- 29016313
TI  - Case Report: Fatal Pediatric Melioidosis Despite Optimal Intensive Care.
AB  - With prompt administration of appropriate antimicrobial therapy and access to
      modern intensive care support, fatal pediatric melioidosis is very unusual. We
      describe cases of two children in whom the possibility of melioidosis was
      recognized relatively early, but who died of the disease, despite receiving
      optimal supportive care. We discuss the resulting implications for bacterial
      virulence factors in disease pathogenesis.

PMID- 29016314
TI  - Case Report: Paralytic Shellfish Poisoning in Sabah, Malaysia.
AB  - During the months of January-February and May-June 2013 coinciding with the red
      tide occurrence in Kota Kinabalu, Sabah, Malaysia, six episodes involving 58
      cases of paralytic shellfish poisoning (PSP) or saxitoxin (STX) poisoning and
      resulting in four deaths were reported. Many of them were intoxicated from
      consuming shellfish purchased from the markets, whereas others were intoxicated
      from eating shellfish collected from the beach. Levels of STX in shellfish
      collected from the affected areas were high (mean 2,920 +/- 780 and 360 +/- 140
      ug STX equivalents/100 g shellfish meat respectively for the two periods). The
      count of toxic dinoflagellates (Pyrodinium bahamense var compressum) of the sea
      water sampled around the coast was also high (mean 34,200 +/- 10,300 cells/L).
      Species of shellfish containing high levels of STX were Atrina fragilis, Perna
      viridis, and Crassostrea belcheri. The age of victims varied from 9 to 67 years.
      Symptoms presented were typical of PSP, such as dizziness, numbness, vomiting,
      and difficulty in breathing. Recommended steps to prevent or reduce PSP in future
      red tide season include better monitoring of red tide occurrence, regular
      sampling of shellfish for determination of STX level, wider dissemination of
      information on the danger of eating contaminated shellfish among the communities,
      fishermen, and fishmongers.

PMID- 29016315
TI  - Case Report: Molecular Confirmation of Lobomycosis in an Italian Traveler
      Acquired in the Amazon Region of Venezuela.
AB  - Lobomycosis is a chronic skin mycosis endemic in Amazon regions characterized by
      chronic nodular or keloidal lesions caused by Lacazia loboi, an uncultivable
      fungus. Imported cases in nonendemic countries are rare and diagnosed after
      years. We describe a case of lobomycosis in a healthy 55-year-old Italian
      traveler who had acquired the infection during 5-day-honeymoon in the Amazon
      region of Venezuela in 1999. Several weeks after return, he recalled pruritus and
      papular skin lesions on the left lower limb, subsequently evolving to a plaque
      like lesion. Blastomycosis and cryptococcosis were hypothesized based on
      microscopic morphology of yeast-like bodies found in three consecutive biopsies,
      although fungal cultures were always negative. In 2016, exfoliative cytology and
      a biopsy specimen examination showed round yeast-like organisms (6-12 MUm),
      isolated or in a chain, connected by short tubular projections fulfilling the
      morphologic diagnostic criteria of Lacazia spp. The microscopic diagnosis was
      confirmed by molecular identification.

PMID- 29016316
TI  - Toxocara Seroprevalence and Associated Risk Factors in the United States.
AB  - Caused by the parasitic nematodes Toxocara canis and cati, toxocariasis in humans
      can result in covert toxocariasis, ocular toxocariasis, visceral larval migrans,
      and neurotoxocariasis. A common infection, toxocariasis exposure varies widely
      within and between countries, with a previous estimate of Toxocara seroprevalence
      using data from 1988 to 1994 in the United States of approximately 13%. Age,
      poverty, sex, educational attainment, ethnicity, and region have been associated
      with Toxocara seroprevalence. In this study, we sought to determine the
      seroprevalence of and factors associated with Toxocara seropositivity in the
      United States using data from the National Health and Nutrition Examination
      Survey from 2011 to 2014 to provide a more recent estimate of Toxocara
      seroprevalence in the United States. We found an overall Toxocara seroprevalence
      of 5.1%. Increasing age, male sex, low educational attainment, low income, and
      immigration status each was associated with Toxocara seropositivity. Mexican
      Americans had reduced odds of exposure. These findings show that exposure to
      Toxocara continues in the United States and that several demographic factors
      influence the risk of exposure.

PMID- 29016317
TI  - Malaria Is More Prevalent Than Iron Deficiency among Anemic Pregnant Women at the
      First Antenatal Visit in Rural South Kivu.
AB  - Anemia is common during pregnancy and is associated with poor outcomes.
      Objectives were not only 1) to determine the prevalence of anemia and iron
      deficiency (ID) but also 2) to identify other factors associated with anemia in
      pregnant women from South Kivu province, in the eastern Democratic Republic of
      Congo. Between December 2013 and March 2014, 531 women attending the first
      antenatal visit in their second trimester of pregnancy were recruited.
      Sociodemographic, clinical, and biological data were collected. Hemoglobin (Hb)
      was determined by a portable photometer (Hemocue(r) Hb201+), and anemia was
      defined as altitude-adjusted Hb < 110 g/L. ID was defined as serum ferritin < 15
      MUg/L adjusted for inflammation status (C-reactive protein [CRP] > 5 mg/L and/or
      alpha-1-acid glycoprotein > 1 g/L) whereas hypoalbuminemia was defined as serum
      albumin < 35 g/L. A Giemsa-stained blood smear was used to diagnose malaria. The
      median age (interquartile range ) was 25.5 (21.1-31.3) years, with anemia in
      17.6% and ID in 8%. Malaria was present in 7.5% and hypoalbuminemia among 44%.
      Soluble transferrin receptor concentration was higher in the presence of
      inflammation and/or malaria. In the final logistic regression model, factors
      independently associated with anemia were malaria (adjusted odds ratio [aOR]:
      11.24 (4.98-25.37) P < 0.001), hypoalbuminemia [aOR: 2.14 (1.27-3.59); P = 0.004]
      and elevated CRP [aOR: 1.94 (1.10-3.45); P = 0.022]. ID was not highly prevalent
      and not associated with anemia in our population. Effective control of anemia
      during pregnancy in this region should consider fighting malaria and other
      infectious diseases in combination with measures to improve women's nutrition,
      both before and during pregnancy.

PMID- 29016319
TI  - Clinical Epidemiology of Septic Arthritis Caused by Burkholderia pseudomallei and
      Other Bacterial Pathogens in Northeast Thailand.
AB  - Septic arthritis is a medical emergency, and if not treated appropriately, it can
      be associated with high morbidity and mortality. Melioidosis, a serious
      infectious disease caused by the Gram-negative bacillus Burkholderia
      pseudomallei, is highly endemic in South and Southeast Asia and northern
      Australia. We reviewed the medical charts of adult patients admitted with
      bacterial septic arthritis at Sunpasitthiprasong Hospital, Ubon Ratchathani,
      northeast Thailand from January 2012 to December 2014. Bacterial septic arthritis
      was defined as one or more hot swollen joints with isolation of a pathogenic
      organism from an affected joint or from blood. A total of 154 patients with
      septic arthritis were retrospectively evaluated. The most common causes were B.
      pseudomallei (48%, N = 74), Streptococcus spp. (29%, N = 44), and Staphylococcus
      aureus (10%, N = 16). Prevalence of diabetes, bacteremia, and pneumonia was
      higher in B. pseudomallei septic arthritis than in septic arthritis caused by the
      other bacteria (all P < 0.01). Seventy three percent (54/74) of patients infected
      with B. pseudomallei and 69% (55/80) of patients with the other bacteria received
      effective antimicrobials on the first day of admission (P = 0.60), but in
      hospital mortality of the former group was considerably higher (34% versus 14%, P
      = 0.004). In conclusion, B. pseudomallei septic arthritis is common and
      associated with high mortality in northeast Thailand. Emergence of Streptococcus
      arthritis is observed. Difficulty in diagnosing melioidosis and identifying B.
      pseudomallei in areas where health care workers are not familiar with the disease
      is discussed. In melioidosis-endemic regions, parenteral ceftazidime could be
      considered as empirical antimicrobial therapy for patients with septic arthritis
      and underlying diseases.

PMID- 29016320
TI  - Comparison of Platforms for Testing Antibody Responses against the Chlamydia
      trachomatis Antigen Pgp3.
AB  - Antibody responses to Chlamydia trachomatis (CT) antigens may be useful tools for
      surveillance of trachoma by estimating cumulative prevalence of infection within
      a population. Data were compared from three different platforms-multiplex bead
      array (MBA), enzyme-linked immunosorbent assay (ELISA), and lateral flow assay
      (LFA)-measuring antibody responses against the CT antigen protein plasmid gene
      product 3 (Pgp3). Sensitivity was defined as the proportion of specimens testing
      antibody positive from a set of dried blood spots from Tanzanian 1-9-year olds
      who were positive for CT nucleic acid of all nucleic acid amplification test
      (NAAT)-positive individuals (N = 103). The sensitivity of the LFA could not be
      determined because of the use of dried blood spots for this test; this specimen
      type has yet to be adapted to LFA. Specificity was defined as the proportion of
      sera from U.S. and Bolivian 1-9-year olds that had previously tested negative by
      the Chlamydia microimmunofluorescence (MIF) assay testing negative to Pgp3
      specific antibodies (N = 154). The sensitivity for MBA and ELISA was the same
      93.2 (95% confidence interval [CI]: 88.3-98.1). Specificity ranged across
      platforms from 96.1 (95% CI: 91.8-98.2) to 99.4% (95% CI: 98.2-100). ELISA
      performance was similar regardless of whether the plates were precoated or
      freshly coated with antigen. Sensitivity and specificity of control panels were
      similar if the cutoff was determined using receiver operator curves or a finite
      mixture model, but the cutoffs themselves differed by approximately 0.5 OD using
      the different methodologies. These platforms show good sensitivity and
      specificity and show good agreement between tests at a population level, but
      indicate variability for ELISA outcomes depending on the cutoff determination
      methodology.

PMID- 29016321
TI  - Nationwide Seroprevalence of Leptospirosis among Young Thai Men, 2007-2008.
AB  - Leptospirosis, a global neglected zoonotic disease, is an important public health
      problem in Thailand. Nonspecific symptoms, lack of laboratory confirmation, and
      underreporting contribute to its neglected disease status. To better understand
      the distribution of leptospirosis exposure in Thailand, a retrospective
      leptospirosis seroprevalence study was conducted on repository serum specimens
      obtained from young Thai men entering the Royal Thai Army during 2007-2008. The
      overall nationwide leptospirosis IgG seroprevalence among these young Thai men
      was 28% (95% confidence interval = 26-30%) and the range by province was 10-52%
      confirming leptospirosis as an endemic disease throughout Thailand.
      Seroprevalence was highest in individuals with the lowest education from rural
      areas, and higher seroprevalence was found in the north and south regions
      contrary to current morbidity reports. Improvement in reporting and surveillance
      as well as better access to leptospirosis diagnostics will increase leptospirosis
      awareness and detection and enable more effective public health interventions.

PMID- 29016318
TI  - Effects of Boiling Drinking Water on Diarrhea and Pathogen-Specific Infections in
      Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.
AB  - Globally, approximately 2 billion people lack microbiologically safe drinking
      water. Boiling is the most prevalent household water treatment method, yet
      evidence of its health impact is limited. To conduct this systematic review, we
      searched four online databases with no limitations on language or publication
      date. Studies were eligible if health outcomes were measured for participants who
      reported consuming boiled and untreated water. We used reported and calculated
      odds ratios (ORs) and random-effects meta-analysis to estimate pathogen-specific
      and pooled effects by organism group and nonspecific diarrhea. Heterogeneity and
      publication bias were assessed using I2, meta-regression, and funnel plots; study
      quality was also assessed. Of the 1,998 records identified, 27 met inclusion
      criteria and reported extractable data. We found evidence of a significant
      protective effect of boiling for Vibrio cholerae infections (OR = 0.31, 95%
      confidence interval [CI] = 0.13-0.79, N = 4 studies), Blastocystis (OR = 0.35,
      95% CI = 0.17-0.69, N = 3), protozoal infections overall (pooled OR = 0.61, 95%
      CI = 0.43-0.86, N = 11), viral infections overall (pooled OR = 0.83, 95% CI = 0.7
      0.98, N = 4), and nonspecific diarrheal outcomes (OR = 0.58, 95% CI = 0.45-0.77,
      N = 7). We found no evidence of a protective effect for helminthic infections.
      Although our study was limited by the use of self-reported boiling and non
      experimental designs, the evidence suggests that boiling provides measureable
      health benefits for pathogens whose transmission routes are primarily water
      based. Consequently, we believe a randomized controlled trial of boiling
      adherence and health outcomes is needed.

PMID- 29016323
TI  - Enzootic Circulation of Chikungunya Virus in East Africa: Serological Evidence in
      Non-human Kenyan Primates.
AB  - Chikungunya virus (CHIKV) is a globally emerging pathogen causing debilitating
      arthralgia and fever in humans. First identified in Tanzania (1953), this
      mosquito-borne alphavirus received little further attention until a 2004 re
      emergence in Kenya from an unknown source. This outbreak subsequently spread to
      the Indian Ocean, with adaptation for transmission by a new urban vector. Under
      the hypothesis that sylvatic progenitor cycles of CHIKV exist in Kenya (as
      reported in West Africa, between non-human primates (NHPs) and arboreal Aedes
      spp. mosquitoes), we pursued evidence of enzootic transmission and human
      spillover events. We initially screened 252 archived NHP sera from Kenya using
      plaque reduction neutralization tests. Given an overall CHIKV seroprevalence of
      13.1% (marginally higher in western Kenya), we sought more recent NHP samples
      during 2014 from sites in Kakamega County, sampling wild blue monkeys, olive
      baboons, and red-tailed monkeys (N = 33). We also sampled 34 yellow baboons near
      Kwale, coastal Kenya. Overall, CHIKV seropositivity in 2014 was 13.4% (9/67).
      Antibodies reactive against closely related o'nyong-nyong virus (ONNV) occurred;
      however, neutralization titers were too low to conclude ONNV exposure.
      Seroprevalence for the flavivirus dengue was also detected (28%), mostly near
      Kwale, suggesting possible spillback from humans to baboons. CHIKV antibodies in
      some juvenile and subadult NHPs suggested recent circulation. We conclude that
      CHIKV is circulating in western Kenya, despite the 2004 human outbreaks only
      being reported coastally. Further work to understand the enzootic ecology of
      CHIKV in east Africa is needed to identify sites of human spillover contact where
      urban transmission may be initiated.

PMID- 29016324
TI  - Hemoglobin Levels and the Risk of Malaria in Papua New Guinean Infants: A Nested
      Cohort Study.
AB  - Studies are available that assess the risk of malaria in accordance to the body's
      iron store and the systematic iron supplementation of preschool children.
      However, only a few studies evaluated the temporal association between hemoglobin
      and malaria and their results are opposing. A total of 1,650 3-month-old Papua
      New Guinean infants were enrolled in this study and followed-up for 12 months.
      The risk of malaria was assessed in all children every 3 months and with each
      episode of fever. The incidence of clinical malaria between 3 and 15 months of
      age was 249 cases per 1,000 infants per year. After adjustment for potential
      confounding factors, a decrease of 1 g/dL of hemoglobin was associated with a
      nonsignificant increase of 11% for risk of malaria infection (hazard ratio, 1.11,
      95% confidence interval; CI, 0.99-1.25, P = 0.076). Only children with severe
      anemia (hemoglobin < 8.0 g/dL) at baseline were at higher risk of malaria
      infection (hazard ratio, 1.72, 95% CI, 1.08-2.76, P = 0.023) during the follow-up
      year compared with the control group (Hemoglobin > 10.0 g/dL). This association
      was not statistically significant if only clinical malaria episodes were taken
      into account (hazard ratio, 1.42, 95% CI, 0.77-2.61, P = 0.26). Our study
      suggests that infants with lower hemoglobin levels are not protected against
      malaria infection. Further research that examines the risk of malaria in relation
      to both hemoglobin and iron store levels would be important to better understand
      this complex interaction.

PMID- 29016325
TI  - Increased Mortality in Seasonal H3N2 Patients Compared with those with Pandemic
      2009 H1N1 in Taiwan, 2009-2010.
AB  - We conducted a retrospective study to compare clinical and laboratory findings
      between 1) severe influenza A and mild influenza A and 2) pandemic 2009 H1N1
      (pdm09 A/H1) and seasonal H3N2 (A/H3) from 2009 to 2010. A total of 526 (mean
      age, 13.6 years; 447 pdm09 A/H1, 79 seasonal A/H3) patients were included, 41
      (7.8%) with severe influenza (mean age, 28.1 years; 26 pdm09 A/H1, 15 seasonal
      A/H3). Influenza-associated complications were pneumonia (75.6%),
      meningoencephalitis (14.6%), acute kidney injury (14.6%), and acute respiratory
      distress syndrome (12.2%). Patients with seasonal A/H3 were significantly less
      likely to experience sore throat (P < 0.001), malaise (P < 0.001), and muscle
      pain (P < 0.001); they were significantly more likely to have hypertension (P <
      0.001), diabetes mellitus (P = 0.001), and chronic obstructive pulmonary disease
      (P < 0.001), delayed hospital presentation (P = 0.001), delayed oseltamivir
      treatment (P < 0.001), and higher in-hospital mortality (P = 0.02) than patients
      with pdm09 A/H1. Further comparison between severe pdm09 A/H1 and severe seasonal
      A/H3 revealed that severe seasonal A/H3 patients (median age, 71 years) were
      significantly older than patients with severe pdm09 A/H1 (median age, 7 years) (P
      < 0.001). Comparison between severe influenza and mild influenza, regardless of
      influenza A subtypes, by multivariate analysis, found that tachypnea (odds ratio
      [OR] = 44.3, 95% confidence interval [CI] = 15.7-124.6) and delayed oseltamivir
      therapy ? 48 hours after illness onset (OR = 3.7, 95% CI = 1.3-10.5) were
      independent risk factors for severe influenza. The findings of this study will
      improve the understanding of the clinical differences between pdm09 A/H1 and
      seasonal A/H3, and of influenza-associated complications and predictors for
      severe outcomes that can help to direct clinicians toward the most effective
      management of influenza patients to reduce the preventable mortality and
      morbidity.

PMID- 29016322
TI  - Demographic, Socioeconomic, and Geographic Factors Leading to Severe Malaria and
      Delayed Care Seeking in Ugandan Children: A Case-Control Study.
AB  - We studied associations between delayed care seeking, demographic, socioeconomic,
      and geographic factors and likelihood of severe malaria in Ugandan children. The
      study was based at Jinja Hospital, Uganda. We enrolled 325 severe malaria cases
      and 325 uncomplicated malaria controls matched by age and residence. Patient
      details, an itinerary of events in response to illness, household information,
      and location of participants' residences were captured. Conditional logistic
      regression was used to determine risk factors for severe malaria and delayed care
      seeking. Delayed care seeking (>= 24 hours after fever onset; odds ratio [OR]
      5.50; 95% confidence interval [CI] 2.70, 11.1), seeking care at a drug shop as
      the initial response to illness (OR 3.62; 95% CI 1.86, 7.03), and increasing
      distance from place of residence to the nearest health center (OR 1.45; 95% CI
      1.17, 1.79) were independent risk factors for severe malaria. On subgroup
      analysis, delayed care seeking was a significant risk factor in children with
      severe malaria attributable to severe anemia (OR 15.6; 95% CI 3.02, 80.6), but
      not unconsciousness (OR 1.13; 95% CI 0.30, 4.28). Seeking care at a drug shop (OR
      2.84; 95% CI 1.12, 7.21) and increasing distance to the nearest health center (OR
      1.18; 95% CI 1.01, 1.37) were independent risk factors for delayed care seeking.
      Delayed care seeking and seeking care at a drug shop were risk factors for severe
      malaria. Seeking care at a drug shop was also a predictor of delayed care
      seeking. The role of drug shops in contributing to delayed care and risk of
      severe malaria requires further study.

PMID- 29016326
TI  - Human Intestinal Parasite Burden and Poor Sanitation in Rural Alabama.
AB  - Hookworm infection affects 430 million people worldwide, causing iron deficiency,
      impaired cognitive development, and stunting in children. Because of the
      environmental conditions needed for the hookworm life-cycle, this parasite is
      endemic to resource-limited countries. Necator americanus was endemic in the
      southern United States before improvement of sewage disposal systems and
      eradication programs. With continued poverty, poor sanitation, and an environment
      suitable for the hookworm life-cycle in some regions of the southern United
      States, a current prevalence study using modern molecular diagnostics is
      warranted. Lowndes County, Alabama, was chosen as the study site given previous
      high hookworm burdens, degree of poverty, and use of open-sewage systems.
      Participants were interviewed, and stool, serum, and soil samples were tested for
      nine intestinal parasites using a multiparallel quantitative real-time PCR (qPCR)
      and enzyme-linked immunosorbent assays. We found that, among 24 households, 42.4%
      reported exposure to raw sewage within their home, and from 55 stool samples, 19
      (34.5%) tested positive for N. americanus, four (7.3%) for Strongyloides
      stercoralis, and one (1.8%) for Entamoeba histolytica. Stool tested positive for
      N. americanus contained low levels of parasite DNA (geometric mean 0.0302
      fg/MUL). Soil studies detected one (2.9%) Cryptosporidium species, and Toxocara
      serology assay detected one (5.2%) positive in this population. Individuals
      living in this high-risk environment within the United States continue to have
      stool samples positive for N. americanus. Gastrointestinal parasites known to be
      endemic to developing countries are identifiable in American poverty regions, and
      areas with lower disease burden are more likely to be identified by using qPCR.

PMID- 29016327
TI  - Molecular and Clinical Epidemiology of Salmonella Paratyphi A Isolated from
      Patients with Bacteremia in Nepal.
AB  - Little is known about the epidemiology of typhoid and paratyphoid fever in Nepal.
      We aimed to elucidate the molecular and clinical epidemiology of Salmonella
      Paratyphi A in Nepal. Isolates were collected from 23 cases of bacteremia due to
      S. Paratyphi A between December 2014 and October 2015. Thirteen patients (57%)
      were male, and the median age was 21 years. None of the patients had an
      underlying chronic disease. All S. Paratyphi A isolates were sensitive to
      ampicillin, trimethoprim/sulfamethoxazole, ceftriaxone, and chloramphenicol. All
      isolates were resistant to nalidixic acid and were categorized as intermediately
      susceptible to levofloxacin. Phylogenetic analysis revealed close relatedness
      among the isolates, including several clonal groups, suggesting local spread.
      Patients with bacteremia due to S. Paratyphi A in Kathmandu, Nepal, were
      relatively young and nondebilitated. Improving control of S. Paratyphi infections
      should focus on effective infection control measures and selection of empirical
      therapy based on current resistance patterns.

PMID- 29016328
TI  - Intralesional Infiltration with Meglumine Antimoniate for the Treatment of
      Leishmaniasis Recidiva Cutis in Ecuador.
AB  - Meglumine Antimoniate (MA), administered intramuscularly for 21 continuous days
      is the recommended treatment of leishmaniases in Ecuador. However, because of its
      toxicity and requirement for intramuscular injections, treatment is frequently
      abandoned before completion. In addition, therapeutic failure and reactivation
      are not uncommon. Here we evaluate the efficacy and safety of MA administered
      intralesionally (IL) in leishmaniasis recidiva cutis (LRC). LRC is a special
      clinical variant of cutaneous leishmaniasis, characterized by reactivation at the
      edges of a primary cured lesion, presenting with active papules around the scar.
      Twenty-one patients were included in the study. All were diagnosed
      parasitologically by one of three diagnostic methods (smear, culture, and
      Leishmanin skin test). Each patient received MA intralesionally weekly for 4
      weeks. Each papule was infiltrated until complete saturation. On average,
      patients received 1 mL of MA per administration. The criterion of cure was the
      complete resolution of the papules. Follow up was performed at 30, 90, and 180
      days after treatment. At day 30 after treatment, 19 (90.5%) of 21 patients were
      clinically cured. The two patients, who did not heal by the fourth application,
      were cured on the seventh and eighth dose, achieving a clinical cure of 100%
      without subsequent reactivation. Mild to moderate local pain during infiltration
      was the only adverse reaction experienced by 81% of patients. In one case,
      subsequent infiltrations were discontinued because of a local allergic reaction.
      Complete compliance of patients to treatment and the small volume of drug
      administered make this method of administering MA an effective, safe, and
      inexpensive alternative. Consequently, IL could replace intramuscular
      administration in the treatment of LRC in Ecuador.

PMID- 29016329
TI  - Preliminary Evaluation of Percutaneous Treatment of Echinococcal Cysts without
      Injection of Scolicidal Agent.
AB  - Puncture, Aspiration, Injection of scolicidal agent, Re-aspiration is the most
      widely used percutaneous treatment of cystic echinococcosis (CE). Among its
      perceived risks is chemical sclerosing cholangitis, a serious complication due to
      the caustic effect of the scolicidal solution on the biliary tree, when a patent
      cystobiliary fistula occurs. To simplify the protocol, we decided to omit
      injection and reaspiration of the scolicidal agent and to implement a full course
      of albendazole (ABZ) therapy instead of the routine 1-month ABZ prophylaxis. We
      searched our databases for patients with CL (Cystic Lesion, suspected for CE),
      CE1, and CE3a cysts treated between October 2007 and January 2017 with
      percutaneous aspiration followed by at least 1 month of oral ABZ and with an
      ultrasound follow-up of at least 6 months. Fifteen patients matched our inclusion
      criteria. Follow-up ranged from 7 to 75 months. The oral ABZ course after the
      aspiration procedure ranged from 1 to 18 months. Eleven subjects (73.3%) had
      undergone a course of ABZ before the percutaneous procedure (min 15 days, max 16
      months). Ten cysts (62.5%) had reached solidification (stage CE4) in 3 to 69
      months. Four other cysts (26.7%) remained stable in stage CE3a, whereas two cysts
      (13.3%) reactivated to stage CE3b. Procedural perioperative complications
      occurred in 13.3% of patients, whereas complications during the follow-up
      occurred in 20% of patients. These proof-of-concept preliminary results are
      overall comparable with those reported in the literature for other percutaneous
      treatments, both in terms of response rate, relapse rate, and morbidity.

PMID- 29016330
TI  - Characterization of Three New Insect-Specific Flaviviruses: Their Relationship to
      the Mosquito-Borne Flavivirus Pathogens.
AB  - Three novel insect-specific flaviviruses, isolated from mosquitoes collected in
      Peru, Malaysia (Sarawak), and the United States, are characterized. The new
      viruses, designated La Tina, Kampung Karu, and Long Pine Key, respectively, are
      antigenically and phylogenetically more similar to the mosquito-borne flavivirus
      pathogens, than to the classical insect-specific viruses like cell fusing agent
      and Culex flavivirus. The potential implications of this relationship and the
      possible uses of these and other arbovirus-related insect-specific flaviviruses
      are reviewed.

PMID- 29016331
TI  - Determining the Cause of Death: Mortality Surveillance Using Verbal Autopsy in
      Indonesia.
AB  - In the absence of a vital registration and health information systems, Indonesia
      does not have complete, accurate, and continuous data to summarize the mortality
      statistics of the population, nor determine the exact cause of death. Verbal
      autopsies performed in a community-based mortality surveillance have been used to
      provide information on the cause of deaths in such context. However, physician
      review of verbal autopsy can be expensive, time-consuming, and give inconsistent
      results, raising concern about its reliability. We used the Purworejo Health and
      Demographic Surveillance System's (HDSS) mortality data collected between 2000
      and 2002 and assigned causes of death for all age groups using Interpreting
      Verbal Autopsy-4, analytic software that applies a probabilistic model. A total
      of 1,999 deaths were identified among 55,581 individuals surveyed in 14,409
      households; 830 deaths were able to be recorded using the standardized World
      Health Organization (WHO) verbal autopsy questionnaire. We calculated the
      proportion of different causes of death and its incidence rate (IR) ratios with
      95% confidence interval (CI) to compare the IR per person-years-observation
      (PYO). The IR of stroke was 126.7 per 100,000 PYO (95% CI: 109.7, 143.7); acute
      respiratory infection including pneumonia was 70.8 per 100,000 PYO (95% CI: 58.1,
      83.5); and the IR of other and unspecified cardiac diseases was 57.7 per 100,000
      PYO (95% CI: 46.2, 69.2). Stroke was indicated as the leading cause of death
      among elderly people aged 50 years and above. Meanwhile, pneumonia as a
      communicable disease was found to be the most common cause of death among both 0
      14-year-old children and elderly people.

PMID- 29016332
TI  - Porcine Cysticercosis: Possible Cross-Reactivity of Taenia hydatigena to GP50
      Antigen in the Enzyme-Linked Immunoelectrotransfer Blot Assay.
AB  - The lentil lectin glycoprotein enzyme-linked immunoelectrotransfer blot (LLGP
      EITB, reported sensitivity 99% and specificity 100%) is used as a serologic
      marker of exposure to Taenia solium in pigs. However, only a limited number of
      parasites have been evaluated for cross reactivity. Pigs may host other related
      cestode infections, including Taenia hydatigena, which have not been formally
      evaluated for cross-reactions. We investigated a corral in Tumbes, Peru, a region
      where a cysticercosis elimination demonstration project was completed in 2012. In
      this corral, 14/19 (73.7%) 6-8-week-old piglets were reactive to GP50 on LLGP
      EITB, and all had circulating Taenia sp. antigens. From eight necropsied piglets;
      four were infected with T. hydatigena metacestodes whereas none had evidence of
      T. solium infection. Two resident dogs were subsequently confirmed to have T.
      hydatigena taeniasis. These results suggest GP50 cross-reactivity in T.
      hydatigena-infected pigs, although controlled experimental infection is needed to
      confirm this hypothesis.

PMID- 29016334
TI  - Spatial Distribution of Pemphigus Occurrence over Five Decades in Southeastern
      Brazil.
AB  - Well-defined locations of pemphigus cases support the hypothesis of environmental
      factors' involvement in its etiopathogenesis; however, these foci have never been
      described using specialized geographical tools. This is the first report to geo
      reference pemphigus cases in a high-prevalence Brazilian region using geographic
      information systems. We aimed to report the spatio-temporal behavior of pemphigus
      foliaceus (PF) and vulgaris (PV) in southeastern Brazil, over the last five
      decades to describe geographical clusters, as well as to characterize the land
      use in the city with the highest number of cases. Patients were identified from
      1965 to 2014. Maps were developed using ArcGIS software and organized into
      decades from 1965 to 2014. Ribeirao Preto was identified as the city with the
      greatest number of cases. Land use was analyzed within a 2 km-buffer surrounding
      the residence of each patient. A total of 426 cases of pemphigus were identified.
      PF was the predominant form (285 cases); notwithstanding, the number of new cases
      of PV rose, overtaking the number of new cases of PF in the last decade studied.
      Agricultural area (42%) and exposed soil (33.2%) are the most predominant land
      uses in Ribeirao Preto surrounding patients' residences. This study shows high
      confidence geographical foci of PF and PV, as well as provides evidence of an
      increase of both clinical forms over the last five decades. All cases of PV and
      PF are in proximity to rivers and agricultural areas which reinforce the
      hypothesis that environmental factors play a role in pemphigus etiopathogenesis.

PMID- 29016333
TI  - Distribution of Mutations Associated with Antifolate and Chloroquine Resistance
      among Imported Plasmodium vivax in the State of Qatar.
AB  - Plasmodium vivax is the most prevalent parasite worldwide, escalating by spread
      of drug resistance. Currently, in Qatar, chloroquine (CQ) plus primaquine are
      recommended for the treatment of P. vivax malaria. The present study examined the
      prevalence of mutations in dihydrofolate reductase (dhfr), dihydropteroate
      synthase (dhps) genes and CQ resistance transporter (crt-o) genes, associated
      with sulphadoxine-pyrimethamine (SP) and chloroquine resistance, among imported
      P. vivax cases in Qatar. Blood samples were collected from patients positive for
      P. vivax and seeking medical treatment at Hamad General Hospital, Doha, during
      2013-2016. The Sanger sequencing method was performed to examine the single
      nucleotide polymorphisms in Pvdhfr, Pvdhps, and Pvcrt-o genes. Of 314 examined P.
      vivax isolates, 247 (78.7%), 294 (93.6%) and 261 (83.1%) were successfully
      amplified and sequenced for Pvdhfr, Pvdhps, and Pvcrt-o, respectively. Overall,
      53.8% (N = 133) carried mutant alleles (58R/117N) in Pvdhfr, whereas 77.2% (N =
      227) and 90% (N = 235) isolates possessed wild type allele in Pvdhps and Pvcrt-o
      genes, respectively. In addition, a total of eleven distinct haplotypes were
      detected in Pvdhfr/Pvdhps genes. Interestingly, K10 insertion in the Pvcrt-o gene
      was observed only in patients originating from the Indian subcontinent. The
      results suggested that CQ remains an acceptable treatment regimen but further
      clinical data are required to assess the effectiveness of CQ and SP in Qatar to
      support the current national treatment guidelines. In addition, limited
      distribution of genetic polymorphisms associated with CQ and SP resistance
      observed in imported P. vivax infections, necessitates regular monitoring of drug
      resistant P. vivax malaria in Qatar.

PMID- 29016337
TI  - The Multifactorial Epidemiology of Blackwater Fever.
AB  - Blackwater fever is a massive hemolytic event usually occurring in the context of
      repeated falciparum malaria infections and intermittent quinine use. Its etiology
      is poorly understood, and it is rarely seen today. Historical epidemiological
      observations from the 20th century demonstrated variable patterns in prisoners in
      Andaman Islands, refugees in Macedonia, canal workers in Panama, expatriates in
      Rhodesia, and Second World War soldiers. Rates of blackwater fever per 1,000
      malaria cases varied over two orders of magnitude. Islands, such as the Andaman
      Islands and New Guinea, had lower blackwater fever rates than continental areas.
      During the Second World War, blackwater fever rates in British soldiers in West
      Africa and Australian soldiers in New Guinea differed by a factor of 40 despite
      similar treatment regimens and falciparum malaria transmission risks. Blackwater
      fever is a complex interaction between host erythrocyte, falciparum malaria, and
      antimalarial drugs which remains poorly understood.

PMID- 29016335
TI  - Performance of Loop-Mediated Isothermal Amplification for the Identification of
      Submicroscopic Plasmodium falciparum Infection in Uganda.
AB  - Accurately identifying and targeting the human reservoir of malaria parasitemia
      is critical for malaria control, and requires a reliable and sensitive diagnostic
      method. Loop-mediated isothermal amplification (LAMP) is increasingly used to
      diagnose submicroscopic parasitemia. Although most published studies report the
      sensitivity of LAMP compared with nested polymerase chain reaction (PCR) as >=
      80%, they have failed to use a consistent, sensitive diagnostic as a comparator.
      We used cross-sectional samples from children and adults in Tororo, Uganda, a
      region with high but declining transmission due to indoor residual spraying, to
      characterize the sensitivity and specificity of pan-Plasmodium LAMP for detecting
      submicroscopic infections. We compared LAMP results targeting a mitochondrial DNA
      sequence conserved in all Plasmodium species, performed on DNA extracted from
      dried blood spots, to those of a gold standard quantitative PCR assay targeting
      the var gene acidic terminal sequence of Plasmodium falciparum (varATS qPCR),
      performed on DNA extracted from 200 uL of whole blood. Using LAMP and varATS qPCR
      increased the detection of parasitemia 2- to 5-fold, compared with microscopy.
      Among microscopy-negative samples, the sensitivity of LAMP was 81.5% for
      detecting infection >= 1 parasites/uL. However, low density infections were
      common, and LAMP failed to identify more than half of all infections diagnosed by
      varATS qPCR, performing with an overall sensitivity of 44.7% for detecting
      submicroscopic infections >= 0.01 parasites/uL. Thus, although the LAMP assay is
      more sensitive than microscopy, it missed a significant portion of the
      submicroscopic reservoir. These findings have important implications for malaria
      control, particularly in settings where low-density infections predominate.

PMID- 29016336
TI  - Efficacy and Safety of a Single-Dose Mebendazole 500 mg Chewable, Rapidly
      Disintegrating Tablet for Ascaris lumbricoides and Trichuris trichiura Infection
      Treatment in Pediatric Patients: A Double-Blind, Randomized, Placebo-Controlled,
      Phase 3 Study.
AB  - This randomized, double-blind, placebo-controlled study evaluated the efficacy
      and safety of a new chewable, rapidly-disintegrating mebendazole (MBZ) 500 mg
      tablet for Ascaris lumbricoides and Trichuris trichiura infection treatment.
      Pediatric patients (1-15 years; N = 295; from Ethiopia and Rwanda) excreting A.
      lumbricoides and/or T. trichiura eggs were enrolled. The study had a screening
      phase (3 days), a double-blind treatment phase (DBP, 19 days), and an open-label
      phase (OLP, 7 days). Patients received MBZ or placebo on day 1 of DBP and open
      label MBZ on day 19 +/- 2 after stool sample collection. Cure rates (primary
      endpoint), defined as species-specific egg count of 0 at the end of DBP, were
      significantly higher in the MBZ group than placebo for A. lumbricoides (83.7%
      [72/86; 95% CI: 74.2%; 90.8%] versus 11.1% [9/81; 95% CI: 5.2%; 20.1%], P <
      0.001) and for T. trichiura (33.9% [42/124; 95% CI: 25.6%; 42.9%] versus 7.6%
      [9/119; 95% CI: 3.5%; 13.9%], P < 0.001). Egg reduction rates (secondary
      endpoint) were significantly higher in the MBZ group than placebo for A.
      lumbricoides (97.9% [95% CI: 94.4; 99.9] versus 19.2% [95% CI: -5.9; 41.5]; P <
      0.001) and T. trichiura (59.7% [95% CI: 33.9; 78.8] versus 10.5% [95% CI: -16.8;
      32.9]; P = 0.003). Treatment-emergent adverse events (TEAEs) in MBZ group
      occurred in 6.3% (9/144) of patients during DBP and 2.5% (7/278) during OLP. No
      deaths, serious TEAEs, or TEAEs leading to discontinuations were reported. A 500
      mg chewable MBZ tablet was more efficacious than placebo for the treatment of A.
      lumbricoides and T. trichiura infections in pediatric patients, and no safety
      concerns were identified.

PMID- 29016338
TI  - A High Burden of Asymptomatic Gastrointestinal Infections in Traditional
      Communities in Papua New Guinea.
AB  - Stool samples were collected from 148 healthy adults living a traditional
      subsistence lifestyle in Papua New Guinea and screened for enteric pathogens
      using real-time RT-PCR/PCR assays. Enteric pathogens were detected in a high
      proportion (41%) of individuals. Clear differences were observed in the detection
      of pathogens between highland and lowland communities. In particular, there was a
      marked difference in detection rates of norovirus GII (20% and 0%, respectively)
      and Shigella sp. (15% and 0%, respectively). Analysis of the relationship between
      enteric pathogen carriage and microbial community composition of participants,
      using box plots to compare specific normal flora population numbers, did not
      suggest that gut microbial composition was directly associated with pathogen
      carriage. This study suggests that enteric pathogens are common in healthy
      individuals in Papua New Guinean highland communities, presumably acting as a
      reservoir of infection and thus contributing to a high burden of gastrointestinal
      illnesses.

PMID- 29016340
TI  - Presence of Burkholderia pseudomallei in Soil and Paddy Rice Water in a Rice
      Field in Northeast Thailand, but Not in Air and Rainwater.
AB  - Environmental Burkholderia pseudomallei has been postulated to be aerosolized
      during ploughing and heavy rain, and could result in inhalational melioidosis.
      Here, we determined the presence of B. pseudomallei in soil, paddy field water
      (PFW), air, and rainwater samples in a single rice paddy field in Ubon
      Ratchathani, northeast Thailand. In 2012, we collected 100 soil samples during
      the dry season, 10 PFW samples during the monsoon season, 77 air samples during
      ploughing (N = 31) and heavy rains (N = 46), and 60 rainwater samples during 12
      rain events. We found that 32 soil samples (32%), six PFW samples (60%), and none
      of the air and rainwater samples were culture positive for B. pseudomallei. Other
      soil bacteria were isolated from air and rainwater samples. Mean quantitative
      count of B. pseudomallei estimated from two culture-positive PFW samples was 200
      colony forming units/mL. Our findings suggest that the risk of melioidosis
      acquisition by inhalation in Thailand might be low.

PMID- 29016339
TI  - Synthetic Antigens Derived from Plasmodium falciparum Sporozoite, Liver, and
      Blood Stages: Naturally Acquired Immune Response and Human Leukocyte Antigen
      Associations in Individuals Living in a Brazilian Endemic Area.
AB  - Peptide vaccine strategies using Plasmodium-derived antigens have emerged as an
      attractive approach against malaria. However, relatively few studies have been
      conducted with malaria-exposed populations from non-African countries. Herein,
      the seroepidemiological profile against Plasmodium falciparum of naturally
      exposed individuals from a Brazilian malaria-endemic area against synthetic
      peptides derived from vaccine candidates circumsporozoite protein (CSP), liver
      stage antigen-1 (LSA-1), erythrocyte binding antigen-175 (EBA-175), and merozoite
      surface protein-3 (MSP-3) was investigated. Moreover, human leukocyte antigen
      (HLA)-DRB1* and HLA-DQB1* were evaluated to characterize genetic modulation of
      humoral responsiveness to these antigens. The study was performed using blood
      samples from 187 individuals living in rural malaria-endemic villages situated
      near Porto Velho, Rondonia State. Specific IgG and IgM antibodies and IgG
      subclasses were detected by enzyme-linked immunosorbent assay, and HLA-DRB1* and
      HLA-DQB1* low-resolution typing was performed by PCR-SSP. All four synthetic
      peptides were broadly recognized by naturally acquired antibodies. Regarding the
      IgG subclass profile, only CSP induced IgG1 and IgG3 antibodies, which is an
      important fact given that the acquisition of protective immunity appears to be
      associated with the cytophilicity of IgG1 and IgG3 antibodies. HLA-DRB1*11 and
      HLA-DQB1*7 had the lowest odds of responding to EBA-175. Our results showed that
      CSP, LSA-1, EBA, and MSP-3 are immunogenic in natural conditions of exposure and
      that anti-EBA antibody responses appear to be modulated by HLA class II antigens.

PMID- 29016341
TI  - Prevalence of Clinical and Subclinical Plasmodium falciparum and Plasmodium vivax
      Malaria in Two Remote Rural Communities on the Myanmar-China Border.
AB  - Malaria infections may be symptomatic, leading to treatment, or "asymptomatic,"
      typically detected through active surveillance, and not leading to treatment.
      Malaria elimination may require purging both types of infection. Using detection
      methods with different sensitivities, we conducted a cross-sectional study in two
      rural communities located along the border between China's Yunnan Province and
      Myanmar's Shan and Kachin States, to estimate the prevalence of asymptomatic and
      symptomatic malaria. In Mong Pawk, all infections detected were asymptomatic, and
      the prevalence of Plasmodium falciparum was 0.3%, 4.3%, 4.0%, and 7.8% by light
      microscopy, rapid diagnostic test (RDT), conventional polymerase chain reaction
      (cPCR), and multiplexed real-time PCR (RT-PCR), respectively, and Plasmodium
      vivax prevalence was 0% by all detection methods. In Laiza, of 385 asymptomatic
      participants, 2.3%, 4.4%, and 12.2% were positive for P. vivax by microscopy,
      cPCR, and RT-PCR, respectively, and 2.3% were P. falciparum-positive only by RT
      PCR. Of 34 symptomatic participants in Laiza, 32.4% were P. vivax-positive by all
      detection methods. Factors associated with infection included gender (males
      higher than females, P = 0.014), and young age group (5-17 age group compared
      with others, P = 0.0024). Although the sensitivity of microscopy was adequate to
      detect symptomatic infections, it missed the vast majority (86.5%) of
      asymptomatic infections. Although molecular detection methods had no advantage
      over standard microscopy or RDT diagnosis for clinically apparent infections,
      malaria elimination along the Myanmar-China border will likely require highly
      sensitive surveillance tools to identify asymptomatic infections and guide
      targeted screen-and-treat interventions.

PMID- 29016342
TI  - Case Report: Histoplasmosis in Himachal Pradesh (India): An Emerging Endemic
      Focus.
AB  - We describe four cases of histoplasmosis indigenous to Himachal Pradesh (India)
      that will be of considerable public health interest. A 48-year-old human
      immunodeficiency virus (HIV)-negative man with cervical and mediastinal
      lymphadenopathy, hepatosplenomegaly, adrenal mass, and bone marrow involvement
      was treated as disseminated tuberculosis without benefit. Progressive
      disseminated histoplasmosis was diagnosed from the fungus in smears from adrenal
      mass. Another 37-year-old HIV-positive man was on treatment of suspected
      pulmonary tuberculosis. He developed numerous erythema nodosum leprosum-like
      mucocutanous lesions accompanied by fever, generalized lymphadenopathy, and
      weight loss. Pulmonary histoplasmosis with cutaneous dissemination was diagnosed
      when skin lesions showed the fungus in smears, histopathology, and mycologic
      culture. Both were successfully treated with amphotericin B/itraconazole. Third
      patient, a 46-year-old HIV-negative man, had oropharyngeal lesions, cervical
      lymphadenopathy, intermittent fever, hepatosplenomegaly, and deteriorating
      general health. Progressive disseminated oropharyngeal histoplasmosis was
      diagnosed from the fungus in smears and mycologic cultures from oropharyngeal
      lesions and cervical lymph node aspirates. He died despite initiating treatment
      with oral itraconazole. Another 32-year-old man 3 months after roadside trauma
      developed a large ulcer with exuberant granulation tissue over left thigh without
      evidence of immunosuppression/systemic involvement. He was treated successfully
      with surgical excision of ulcer under amphotericin B/itraconazole coverage as
      primary cutaneous histoplasmosis confirmed pathologically and mycologically. A
      clinical suspicion remains paramount for early diagnosis of histoplasmosis
      particularly in a nonendemic area. Most importantly, with such diverse clinical
      presentation and therapeutic outcome selection of an appropriate and customized
      treatment schedule is a discretion the treating clinicians need to make.

PMID- 29016345
TI  - ?

PMID- 29016344
TI  - Defining Persistent Hotspots: Areas That Fail to Decrease Meaningfully in
      Prevalence after Multiple Years of Mass Drug Administration with Praziquantel for
      Control of Schistosomiasis.
AB  - Preventive chemotherapy with praziquantel for schistosomiasis morbidity control
      is commonly done by mass drug administration (MDA). MDA regimen is usually based
      on prevalence in a given area, and effectiveness is evaluated by decreases in
      prevalence and/or intensity of infection after several years of implementation.
      Multiple studies and programs now find that even within well-implemented,
      multiyear, annual MDA programs there often remain locations that do not decline
      in prevalence and/or intensity to expected levels. We term such locations
      "persistent hotspots." To study and address persistent hotspots, investigators
      and neglected tropical disease (NTD) program managers need to define them based
      on changes in prevalence and/or intensity. But how should the data be analyzed to
      define a persistent hotspot? We have analyzed a dataset from an operational
      research study in western Tanzania after three annual MDAs using four different
      approaches to define persistent hotspots. The four approaches are 1) absolute
      percent change in prevalence; 2) percent change in prevalence; 3) change in World
      Health Organization guideline categories; 4) change (absolute or percent) in both
      prevalence and intensity. We compare and contrast the outcomes of these analyses.
      Our intent is to show how the same dataset yields different numbers of persistent
      hotspots depending on the approach used to define them. We suggest that
      investigators and NTD program managers use the approach most suited for their
      study or program, but whichever approach is used, it should be clearly stated so
      that comparisons can be made within and between studies and programs.

PMID- 29016343
TI  - Passively versus Actively Detected Malaria: Similar Genetic Diversity but
      Different Complexity of Infection.
AB  - The surveillance of malaria is generally undertaken on the assumption that
      samples passively collected at health facilities are comparable to or
      representative of the broader Plasmodium reservoir circulating in the community.
      Further characterization and comparability of the hidden asymptomatic parasite
      reservoir are needed to inform on the potential impact of sampling bias. This
      study explores the impact of sampling strategy on molecular surveillance by
      comparing the genetic make-up of Plasmodium falciparum and Plasmodium vivax
      isolates collected by passive versus active case detection. Sympatric isolates of
      P. falciparum and P. vivax were collected from a large community survey and
      ongoing clinical surveillance studies undertaken in the hypomesoendemic setting
      of Mimika District (Papua, Indonesia). Plasmodium falciparum isolates were
      genotyped at nine microsatellite loci and P. vivax at eight loci. Measures of
      diversity and differentiation were used to compare different patient and
      parasitological sample groups. The results demonstrated that passively detected
      cases (symptomatic) had comparable population diversity to those circulating in
      the community (asymptomatic) in both species. In addition, asymptomatic patent
      infections were as diverse as subpatent infections. However, a significant
      difference in multiplicity of infection (MOI) and percentage of polyclonal
      infections was observed between actively and passively detected P. vivax cases
      (mean MOI: 1.7 +/- 0.7 versus 1.4 +/- 1.4, respectively; P = 0.001). The study
      findings infer that, in hypomesoendemic settings, passive sampling is appropriate
      for molecular parasite surveillance strategies using the predominant clone in any
      given infection; however, the findings suggest caution when analyzing complexity
      of infection. Further evaluation is required in other endemic settings.

PMID- 29016346
TI  - Nonsteroidal Anti-Inflammatory Drugs in Patients with Anorexia-Cachexia Syndrome
      Associated with Malignancy and Its Treatments.

PMID- 29016347
TI  - Omega-3 Fatty Acids in Patients with Anorexia-Cachexia Syndrome Associated with
      Malignancy and Its Treatments.

PMID- 29016348
TI  - PARP-1 and PARP-2 activity in cancer-induced cachexia: potential therapeutic
      implications.
AB  - Skeletal muscle dysfunction and mass loss is a characteristic feature in patients
      with chronic diseases including cancer and acute conditions such as critical
      illness. Maintenance of an adequate muscle mass is crucial for the patients'
      prognosis irrespective of the underlying condition. Moreover, aging-related
      sarcopenia may further aggravate the muscle wasting process associated with
      chronic diseases and cancer. Poly(adenosine diphosphate-ribose) polymerase (PARP)
      activation has been demonstrated to contribute to the pathophysiology of muscle
      mass loss and dysfunction in animal models of cancer-induced cachexia. Genetic
      inhibition of PARP activity attenuated the deleterious effects seen on depleted
      muscles in mouse models of oncologic cachexia. In the present minireview the
      mechanisms whereby PARP activity inhibition may improve muscle mass and
      performance in models of cancer-induced cachexia are discussed. Specifically, the
      beneficial effects of inhibition of PARP activity on attenuation of increased
      oxidative stress, protein catabolism, poor muscle anabolism and mitochondrial
      content and epigenetic modulation of muscle phenotype are reviewed in this
      article. Finally, the potential therapeutic strategies of pharmacological PARP
      activity inhibition for the treatment of cancer-induced cachexia are also being
      described in this review.

PMID- 29016349
TI  - Structural mechanisms of HECT-type ubiquitin ligases.
AB  - Ubiquitin ligases (E3 enzymes) transfer ubiquitin from ubiquitin-conjugating (E2)
      enzymes to target proteins. By determining the selection of target proteins,
      modification sites on those target proteins, and the types of ubiquitin
      modifications that are formed, E3 enzymes are key specificity factors in
      ubiquitin signaling. Here, I summarize our knowledge of the structural mechanisms
      in the HECT E3 subfamily, many members of which play important roles in human
      disease. I discuss interactions of the conserved HECT domain with E2 enzymes,
      ubiquitin and target proteins, as well as macromolecular interactions with
      regulatory functions. While we understand individual steps in the catalytic cycle
      of HECT E3 enzymes on a structural level, this review also highlights key aspects
      that have yet to be elucidated. For instance, it remains unclear how diverse
      target proteins are presented to the catalytic center and how certain HECT E3
      enzymes achieve specificity in ubiquitin linkage formation. The structural and
      functional properties of the N-terminal regions of HECT E3 enzymes that likely
      act as signaling hubs are also largely unknown. Structural insights into these
      aspects may open up routes for a therapeutic intervention with specific HECT E3
      functions in distinct pathophysiological settings.

PMID- 29016350
TI  - A novel design of HA-coated nanoparticles co-encapsulating plasmid METase and 5
      Fu shows enhanced application in targeting gastric cancer stem cells.
AB  - Nanoparticles (NPs) are recognized as an attractive vehicles for cancer treatment
      due to their targeted drug release. Gastric cancer is an important killer
      disease, and its therapy methods still need improvement. The NPs were prepared
      using a precipitation method, and were evaluated using transmission electron
      microscopy (TEM). MTT and Transwell assays were used to determine cell viability
      and apoptosis. In vivo experiments were performed to validate the effects of NPs
      on tumor growth. Methioninase (METase)/5-Fu co-encaspulated NPs showed highest
      zeta size and lowest zeta potential than other NPs. The migration and tumorsphere
      formation ability of CD44(+) was stronger than CD44(-). The effects of METase/5
      Fu co-encaspulated NPs on inhibition cell growth was stronger than that of 5-Fu
      encaspulated NPs, while HA coated NPs showed significant target ability than that
      NPs without HA. METase supplementation promoted the inhibition effect of 5-Fu on
      thymidylate synthetase (TS), as well as cell apoptosis. The in vivo experiments
      demonstrated that HA coated NPs significantly inhibited tumor growth. It was
      concluded that HA-coated NPs enhance the target ability, while METase/5-Fu co
      encaspulated NPs promote the inhibition effects on tumor growth in gastric
      cancer.

PMID- 29016351
TI  - Ameliorative effect of gallic acid on doxorubicin-induced cardiac dysfunction in
      rats.
AB  - BACKGROUND: The use of doxorubicin (DOX) as an antineoplastic agent has been
      greatly limited because of the myriad of toxic sequelae associated with it. The
      aim of this study was to assess the protective effects of gallic acid (GA) on DOX
      induced cardiac toxicity in rats. METHODS: Sixty male rats (Wistar strain) were
      used in this study. They were divided into six groups (A-F) each containing 10
      animals. Group A was the control. Rats in Groups B, C, and D were treated with
      DOX at the dosage of 15 mg/kg body weight i.p. Prior to this treatment, rats in
      Groups C and D had been treated orally with GA for 7 days at the dosage of 60 and
      120 mg/kg, respectively. Animals from Groups E and F received only 60 and 120
      mg/kg GA, respectively, which were administered orally for 7 days. RESULTS: The
      exposure of rats to DOX led to a significant (p<0.05) decrease in the cardiac
      antioxidant defence system and elevation of creatine kinase myocardial band and
      lactate dehydrogenase. The electrocardiography results showed a significant
      decrease in heart rate, QRS, and QT-segment prolongation. GA alone improved the
      antioxidant defence system. CONCLUSIONS: The GA pretreatment significantly
      alleviated GA-associated ECG abnormalities, restored the antioxidant status and
      prevented cardiac damage.

PMID- 29016352
TI  - In vitro ovicidal activity of poly lactic acid curcumin-nisin co-entrapped
      nanoparticle against Fasciola spp. eggs and its reproductive toxicity.
AB  - BACKGROUND: Curcumin and nisin have been widely reported for their antibacterial
      and anticancer potency. However, their therapeutic applications are hampered by
      several factors, which necessitate their development into nanosize ranges for
      improved delivery and activities. Their incorporation into a single
      nanosynthesized form may suggest desirable efficacy on parasites. The aim of the
      study was to assess the ovicidal activity of the curcumin-nisin polylactic acid
      (PLA) entrapped nanoparticle on the Fasciola eggs and its reproductive toxicity.
      METHODS: The nanoparticle was formulated by double emulsion method. The eggs of
      the adult Fasciola spp. were exposed to different concentrations (0.3125-5 mg/mL)
      of the nanoparticle to monitor hatchability. Mice were exposed to 0.5 mL of the
      formulated drug at varying concentrations (10-20 mg/kg) and then sacrificed for
      sperm morphology assay. RESULTS: The mean particle size, polydispersity index,
      and drug entrapment efficiency of the formulated drug were 288.4+/-24.3 nm,
      0.232, and 51.7%, respectively. The highest nanoparticulate concentration (5
      mg/mL) showed the least percentage egg hatching (41.7%) compared with the other
      treatment groups and positive control (albendazole) (45.1%). The aberrations
      observed in sperm cells were not concentration-dependent and no significant
      differences were observed in the mean aberrations between the nanoparticulate
      drug-exposed groups and the negative control (p>0.05). CONCLUSIONS: The results
      confirmed the ovicidal activity of the curcumin-nisin nanoparticulate drug
      against the Fasciola species. The formulation also showed no toxicity to sperm
      cells. More robust studies on anti-fascioliasis activity of the drug on adult
      Fasciola spp. and in vivo and in vitro toxicity studies are recommended.

PMID- 29016353
TI  - Markers influencing the presence of partial clinical remission in patients with
      newly diagnosed type 1 diabetes.
AB  - BACKGROUND: The aim of the study was to compare the selected markers in children
      with and without partial clinical remission (CR) of newly diagnosed type 1
      diabetes (T1D). METHODS: The study group consisted of 186 patients (F/M; 87/99)
      at onset of T1D and 24 months of follow-up. Partial CR was defined as insulin
      requirement <0.5 IU/kg and glycated hemoglobin (HbA1c) <7%. RESULTS: Partial CR
      was observed in 115/186 (61.83%) of patients. At diagnosis body mass index
      standard deviation (BMI SDS) was higher among remitters than in non-remitters
      (p=0.0051) and remitters were younger (p=0.0029). In the follow-up a higher
      triglyceride concentration in non-remitters compared to remitters (p=0.0455) and
      a lower high density lipoprotein (HDL) cholesterol level (p=0.0119) were noticed.
      CONCLUSIONS: Younger age and higher BMI at diagnosis of T1D can predispose to
      partial CR in children. In patients with CR of T1D after 2 years of follow-up a
      lipid profile improvement is observed.

PMID- 29016354
TI  - Congenital cataract with LSS gene mutations: a new case report.
AB  - BACKGROUND: Congenital cataract is one of the major causes of blindness and
      amblyopia in children. About one-third of the cases are inherited. CASE
      PRESENTATION: We applied whole exome sequencing for a pediatric patient with
      congenital cataract, small penis, baldness and absence of eyebrows and detected a
      compound heterozygous mutation in the lanosterol synthase (LSS) gene. These two
      mutations were inherited from the patient's parents. Both mutations altered the
      amino acid coding, at highly conserved amino acid residues. CONCLUSIONS: We
      concluded that the mutations affect the structural stability of the protein to
      some extent.

PMID- 29016355
TI  - Genetic analysis of fructose-1,6-bisphosphatase (FBPase) deficiency in nine
      consanguineous Pakistani families.
AB  - BACKGROUND: Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare inherited
      metabolic disorder characterized by recurrent episodes of hypoglycemia, ketosis
      and lactic acidosis. FBPase is encoded by FBP1 gene and catalyzes the hydrolysis
      of fructose-1,6-bisphosphate to fructose-6-phosphate in the last step of
      gluconeogenesis. We report here FBP1 mutations in nine consanguineous Pakistani
      families affected with FBPase deficiency. METHODS: Nine families having one or
      two individuals affected with FBPase deficiency were enrolled over a period of 3
      years. All FBP1 exonic regions including splicing sites were PCR-amplified and
      sequenced bidirectionally. Familial cosegregation of mutations with disease was
      confirmed by direct sequencing and PCR-RFLP analysis. RESULTS: Three different
      FBP1 mutations were identified. Each of two previously reported mutations
      (c.472C>T (p.Arg158Trp) and c.841G>A (p.Glu281Lys)) was carried by four different
      families. The ninth family carried a novel 4-bp deletion (c.609_612delAAAA),
      which is predicted to result in frameshift (p.Lys204Argfs*72) and loss of FBPase
      function. The novel variant was not detected in any of 120 chromosomes from
      normal ethnically matched individuals. CONCLUSIONS: FBPase deficiency is often
      fatal in the infancy and early childhood. Early diagnosis and prompt treatment is
      therefore crucial to preventing early mortality. We recommend the use of c.472C>T
      and c.841G>A mutations as first choice genetic markers for molecular diagnosis of
      FBPase deficiency in Pakistan.

PMID- 29016356
TI  - Decline in lung function among cement production workers: a meta-analysis.
AB  - BACKGROUND: Several studies with different results have been performed regarding
      cement dust exposure and its pathogenic outcomes during the previous years. This
      study aims to combine these results to obtain a reliable estimate of the effect
      of exposure to cement dust. METHODS: PubMed and other data banks were searched to
      identify required electronic articles. The search was extended interviewing with
      relevant experts and research centers. Point and pooled estimates of outcome with
      95% confidence intervals were estimated. RESULTS: Participants were 5371 exposed
      and 2650 unexposed persons. Total mean differences (95% confidence intervals)
      were estimated as of -0.48 (-0.71 to -0.25) L for forced vital capacity (FVC), 
      0.7 (-0.92 to -0.47) L for forced expiratory volume in the first second (FEV1), 
      0.43 (-0.68 to -0.19) L for FEV1/FVC%, -0.73 (-1.15 to -0.30) L/min for PEFR and 
      0.36 (-0.51 to -0.21) L/s for FEF25-75. CONCLUSION: Our meta-analysis showed that
      cement dust has significant impact on lung function and reduces the indicators of
      FVC, FEV1, FEV1/FVC, PEFR and FEF25-75.

PMID- 29016357
TI  - Corrigendum to: Ginkgetin inhibits proliferation of human leukemia cells via the
      TNF-alpha signaling pathway.

PMID- 29016358
TI  - CA125 effects on humoral immunosuppression.

PMID- 29016361
TI  - Contraction, cation oxidation state and size effects in cerium oxide
      nanoparticles.
AB  - An accurate description of the structural and chemical modifications of cerium
      oxide nanoparticles (NPs) is mandatory for understanding their functionality in
      applications. In this work we investigate the relation between local atomic
      structure, oxidation state, defectivity and size in cerium oxide NPs with
      variable diameter below 10 nm, using x-ray absorption fine structure analysis in
      the near and extended energy range. The NPs are prepared by physical methods
      under controlled conditions and analyzed in morphology and crystalline quality by
      high resolution transmission electron microscopy. We resolve here an important
      question on the local structure of cerium oxide NPs: we demonstrate a progressive
      contraction in the Ce-O interatomic distance with decreasing NP diameter and we
      relate the observed effect to the reduced dimensionality. The contraction is not
      significantly modified by inducing a 4%-6% higher Ce3+ concentration through
      thermal annealing in high vacuum. The consequences of the observed average cation
      anion distance contraction on the properties of the NPs are discussed.

PMID- 29016362
TI  - Compression deformation of WC: atomistic description of hard ceramic material.
AB  - The deformation characteristics of WC, as a typical hard ceramic material, were
      studied on the nanoscale using atomistic simulations for both the single-crystal
      and polycrystalline forms under uniaxial compression. In particular, the effects
      of crystallographic orientation, grain boundary coordination and grain size on
      the origin of deformation were investigated. The deformation behavior of the
      single-crystal and polycrystalline WC both depend strongly on the orientation
      towards the loading direction. The grain boundaries play a significant role in
      the deformation coordination and the potential high fracture toughness of the
      nanocrystalline WC. In contrast to conventional knowledge of ceramics, maximum
      strength was obtained at a critical grain size corresponding to the turning point
      from a Hall-Petch to an inverse Hall-Petch relationship. For this the mechanism
      of the combined effect of dislocation motion within grains and the coordination
      of stress concentration at the grain boundaries were proposed. The present work
      has moved forward our understanding of plastic deformability and the possibility
      of achieving a high strength of nanocrystalline ceramic materials.

PMID- 29016360
TI  - PKCzeta-dependent upregulation of p27kip1 contributes to oxidative stress induced
      retinal pigment epithelial cell multinucleation.
AB  - Retinal pigment epithelial (RPE) cells increase in size and multinucleate during
      aging. We have shown using human and mouse cell lines that oxidised photoreceptor
      outer segments (oxPOS)-induced cytokinesis failure is related to RPE cell
      multinucleation, although the underlying mechanism remains unknown. This study
      investigated the role of the PKC pathway in oxPOS-induced RPE multinucleation
      using ARPE19 cells. oxPOS treatment promoted PKC activity and upregulated the
      mRNA expression of PKC alpha, delta, zeta, iota and MU. Inhibition of PKCalpha
      with Go6976 resulted in a 33% reduction of multinucleate ARPE19 cells, whereas
      inhibition of PKCzeta with Go6983 led to a 50% reduction in multinucleate ARPE19
      cells. Furthermore, oxPOS treatment induced a PKCzeta-dependent upregulation of
      the Cdk inhibitor p27kip1, its inhibition using A2CE reduced oxPOS-induced ARPE19
      multinucleation. Our results suggest that oxPOS-induced ARPE19 cytokinesis
      failure is, at least in part, due to the upregulation of p27kip1 through
      activating the PKC, particularly PKCzeta pathway. Targeting the PKCzeta-p27kip1
      signalling axis may be a novel approach to restore RPE repair capacity during
      aging.

PMID- 29016359
TI  - Age-related gene expression in luminal epithelial cells is driven by a
      microenvironment made from myoepithelial cells.
AB  - Luminal epithelial cells in the breast gradually alter gene and protein
      expression with age, appearing to lose lineage-specificity by acquiring
      myoepithelial-like characteristics. We hypothesize that the luminal lineage is
      particularly sensitive to microenvironment changes, and age-related
      microenvironment changes cause altered luminal cell phenotypes. To evaluate the
      effects of different microenvironments on the fidelity of epigenetically
      regulated luminal and myoepithelial gene expression, we generated a set of
      lineage-specific probes for genes that are controlled through DNA methylation.
      Culturing primary luminal cells under conditions that favor myoepithelial
      propogation led to their reprogramming at the level of gene methylation, and to a
      more myoepithelial-like expression profile. Primary luminal cells' lineage
      specific gene expression could be maintained when they were cultured as bilayers
      with primary myoepithelial cells. Isogenic stromal fibroblast co-cultures were
      unable to maintain the luminal phenotype. Mixed-age luminal-myoepithelial
      bilayers revealed that luminal cells adopt transcription and methylation patterns
      consistent with the chronological age of the myoepithelial cells. We provide
      evidence that the luminal epithelial phenotype is exquisitely sensitive to
      microenvironment conditions, and that states of aging are cell non-autonomously
      communicated through microenvironment cues over at least one cell diameter.

PMID- 29016363
TI  - Hillocks created for amorphizable and non-amorphizable ceramics irradiated with
      swift heavy ions: TEM study.
AB  - In a previous study, we found that hillocks (i.e. surface ion tracks) can be
      imaged using transmission electron microscopy (TEM) by irradiating thin CeO2
      samples with swift heavy ions (SHI) at oblique incidence. In the present study,
      the same TEM method is applied to Y3Fe5O12 (YIG) and three fluorides (CaF2, SrF2
      and BaF2) for observing hillocks. For YIG, which is one of the amorphizable
      materials, hillocks are found to have amorphous features consistent with
      amorphous features of ion tracks. For the fluorides, it is found that the
      hillocks do not exhibit amorphous features, and they are composed of
      nanocrystallites. Although hillocks for YIG and CaF2 exhibit different
      crystallographic features, hillock diameter agrees with the molten region
      diameter predicted by the thermal spike model for both materials. It is found
      that for YIG the hillock diameter is comparable to the ion track diameter,
      whereas for the fluorides it is always larger than the ion track diameter. The
      present result shows the existence of the velocity effect for ion track diameter
      in CaF2. It is also found that for fluorides both hillock and ion track diameters
      vary in the order of cation mass (i.e. CaF2 < SrF2 < BaF2). The above results of
      hillocks and ion tracks for SHI-irradiated fluorides can be consistently
      interpreted within the framework of the thermal spike model, if melting and
      successive recrystallization are assumed.

PMID- 29016364
TI  - Burnout and Psychological Distress Among Pediatric Critical Care Physicians in
      the United States.
AB  - OBJECTIVES: To estimate the prevalence of physician burnout, psychological
      distress, and its association with selected personal and practice characteristics
      among pediatric critical care physicians and to evaluate the relationship between
      burnout and psychological distress. DESIGN: Cross-sectional, online survey.
      SETTING: Pediatric critical care practices in the United States. SUBJECTS:
      Pediatric critical care physicians. INTERVENTIONS: None. MEASUREMENT AND MAIN
      RESULTS: A nonrandom sample of 253 physicians completed an online survey
      consisting of personal and practice characteristics, the Maslach Burnout
      Inventory, and the General Health Questionnaire. Nearly half of the participants
      (49%; 95% CI, 43-55%; n = 124) scored high burnout in at least one of the three
      subscales of the Maslach Burnout Inventory and 21% reported severe burnout. The
      risk of any burnout was about two times more in women physicians (odds ratio,
      1.97; 95% CI, 1.2-3.4). Association between other personal or practice
      characteristics and burnout was not evident in this study, while regular physical
      exercise appeared to be protective. One third of all participants (30.5%) and 69%
      of those who experienced severe burnout screened positive for psychological
      distress. About 90% of the physicians reporting severe burnout have considered
      leaving their practice. CONCLUSIONS: Burnout is high among pediatric critical
      care physicians in the United States. About two thirds of the physicians with
      severe burnout met the screening criteria for psychological distress that
      suggests possible common mental disorders. Significant percentages of physicians
      experiencing burnout and considering to leave the profession has major
      implications for the critical care workforce.

PMID- 29016365
TI  - Spleen and liver injuries: when to operate?
AB  - PURPOSE OF REVIEW: Although nonoperative management (NOM) is the safest option in
      most patients with liver and splenic injuries or splenic injuries, some cases
      still need operative intervention. The aim of this review is to address the most
      recent literature and the evidence it provides for indications and timing of
      operative treatment for liver and spleen injuries. RECENT FINDINGS: There seems
      to be a decrease in publication rate on these topics over the last years,
      parallel to the acceptance of NOM as the 'gold standard', with little added to
      the existing body of evidence over the last 12-24 months. Most published studies
      are retrospective descriptions or comparisons with historical controls, some
      observational studies, but no randomized control trials (RCTs).There is a
      striking lack of high-level evidence for the optimal treatment of solid organ
      injuries. The role of angiographic embolization as an adjunct to the treatment of
      liver and spleen injuries is still a matter of discussion. SUMMARY: Unstable
      patients with suspected ongoing bleeding from liver and spleen injuries or spleen
      injuries with inadequate effect of resuscitation should undergo immediate
      explorative laparotomy.More RCTs are needed to further determine the role of
      angiographic embolization and who can be safely be treated nonoperatively and who
      needs surgical intervention.

PMID- 29016366
TI  - Acute life-threatening hypoxemia during mechanical ventilation.
AB  - PURPOSE OF REVIEW: To describe current evidence-based practice in the management
      of acute life-threatening hypoxemia in mechanically ventilated patients and some
      of the methods used to individualize the care of the patient. RECENT FINDINGS:
      Patients with acute life-threatening hypoxemia will often meet criteria for
      severe ARDS, for which there are only a few treatment strategies that have been
      shown to improve survival outcomes. Recent findings have increased our knowledge
      of the physiological effects of spontaneous breathing and the application of
      PEEP. Additionally, the use of advanced bedside monitoring has a promising future
      in the management of hypoxemic patients to fine-tune the ventilator and to
      evaluate the individual patient response to therapy. SUMMARY: Treating the
      patient with acute life-threatening hypoxemia during mechanical ventilation
      should begin with an evidence-based approach, with the goal of improving
      oxygenation and minimizing the harmful effects of mechanical ventilation. The use
      of advanced monitoring and the application of simple maneuvers at the bedside may
      assist clinicians to better individualize treatment and improve clinical
      outcomes.

PMID- 29016367
TI  - Updates in nutrition and polypharmacy.
AB  - PURPOSE OF REVIEW: Medications have the potential to affect nutritional status in
      negative ways, especially as the number of medications increase. The inter
      relation between polypharmacy and malnutrition is complex and not fully
      delineated in previous studies. More research has been done and compiled in the
      last year, which helps to clarify this relationship. This review brings together
      the most recent literature with the previous research to help healthcare
      providers to better assess and manage medication therapy in older adults. RECENT
      FINDINGS: Recent evidence confirms a synergistic negative effect of polypharmacy
      and malnutrition on outcomes of older adults. In addition, several drug classes,
      including common antihypertensive agents, acetylcholinesterase inhibitors,
      multivitamins, proton pump inhibitors, HMG-CoA reductase inhibitors (statins),
      antiplatelet agents and metformin, have been implicated in important drug
      nutrient interactions. These are reviewed in detail here. Ongoing research
      endeavors are described. SUMMARY: Healthcare practitioners can use this review to
      identify potentially inappropriate medications and patients at highest risk of
      experiencing a medication-related adverse reaction in order to systematically
      deprescribe these high-risk medications.

PMID- 29016368
TI  - Perioperative point of care ultrasound in ambulatory anesthesia: thinking beyond
      nerve blocks.
AB  - PURPOSE OF REVIEW: Ultrasound has become readily available in the perioperative
      area. In this review, we aim to bring forth some uses of ultrasound beyond that
      in regional anesthesia. RECENT FINDINGS: Critical care and emergency physicians
      have embraced ultrasound in their respective fields. We as anesthesiologists and
      practitioners of acute care medicine are not immune to this penetration. There is
      been a lot of recent literature on the various uses of perioperative point of
      care ultrasound. Our review summarizes the recent data and provides the reader
      with an overall idea of the uses of ultrasound in the perioperative arena.
      SUMMARY: Focus towards improving patient outcomes is the goal of all physicians
      and point of care ultrasound is one modality that can help us manage some common
      conditions in the perioperative period. Perioperative point of care ultrasound
      training may soon become a prerequisite for an anesthesiology residency.

PMID- 29016369
TI  - Newly developed left ventricular apical thrombus under dabigatran treatment.
AB  - : Left ventricular (LV) thrombi are mostly formed in the aneurysmal or akinetic
      segment of the LV apex. Thromboembolism to the brain is usually fatal. There is
      not enough information available regarding the use of these new oral
      anticoagulant agents in LV thrombi. In this case, we present a 56-year-old male
      patient who was given dabigatran (150 mg, twice a day) for paroxysmal atrial
      fibrillation after experiencing anterior myocardial infarction. During the use of
      dabigatran, thrombus formation, which was not present earlier, was observed in
      the LV apical aneurysm. The dabigatran treatment discontinued and warfarin was
      initiated and, in the follow-ups, the thrombus was observed to shrink, and
      complete resolution was seen 6 weeks after treatment with warfarin. The patient
      did not experience any thromboembolic event. Our case is the first report showing
      that the treatment of dabigatran 150 mg may not prevent LV thrombus development.

PMID- 29016370
TI  - Heavily Calcified Coronary Arteries: Advanced Calcium Subtraction Improves
      Luminal Visualization and Diagnostic Confidence in Dual-Energy Coronary Computed
      Tomography Angiography.
AB  - OBJECTIVES: The aim of this study was to evaluate a prototype dual-energy
      computed tomography calcium subtraction algorithm and its impact on luminal
      visualization in patients with heavily calcified coronary arteries. MATERIALS AND
      METHODS: Twenty-nine patients (62% male; mean age, 64 +/- 7 years) who had
      undergone dual-energy coronary computed tomography angiography were
      retrospectively included in this institutional review board-approved, Health
      Insurance Portability and Accountability Act-compliant study. Linearly blended
      (M_0.6) and calcium-subtracted images were reconstructed. Two independent
      observers assessed luminal visualization of the coronary arteries in a segment
      based analysis, subjective image quality, and diagnostic confidence using 5-point
      Likert scales. Contrast-to-noise ratios for both data sets were calculated.
      Wilcoxon testing and Cohen's kappa were used for statistical comparisons.
      RESULTS: Calcium-subtracted image series showed improved lumen visualization of
      the coronary arteries (P = 0.008), with excellent interreader agreement (mean
      score, 3.3; kappa = 0.82), compared with M_0.6 series (mean score, 2.9; kappa =
      0.77). The calcium subtraction algorithm improved diagnostic confidence compared
      with the M_0.6 reconstructions (mean scores, 4.0 and 3.1, respectively; all P <=
      0.002). The image quality analysis showed no significant differences between
      calcium-subtracted and M_0.6 data sets (subjectively: mean scores, 4.1 and 4.2,
      respectively, P = 0.442; objectively: mean contrast-to-noise ratio, 37.0 and
      38.2, respectively, P = 0.733). CONCLUSIONS: A prototype algorithm for calcium
      subtraction improves coronary lumen visualization and diagnostic confidence in
      patients with heavy coronary calcifications without differences in conventional
      subjective and objective measures of image quality.

PMID- 29016372
TI  - The Peculiar Case of a Large Right Lower Quadrant Solitary Fibrous Tumor With
      Vasculature Arising from the Splenic Artery and Vein.
AB  - We present the interesting case of a patient with peritoneal solitary fibrous
      tumor (SFT). The patient initially presented with right lower quadrant pain.
      Computed tomography findings revealed the presence of a large mass near the
      cecum, with both arterial and venous blood supply arising directly from the
      splenic artery and vein. The patient ultimately underwent surgical excision of
      the mass, and pathological examination was consistent with benign SFT. Not only
      is the location of our patient's tumor exceedingly rare, but also, to our
      knowledge, it is the first reported case of SFT with such a unique vascular
      supply.

PMID- 29016371
TI  - Inflammation in bone physiology and pathology.
AB  - PURPOSE OF REVIEW: Bone is constantly being remodeled throughout adult life
      through constant anabolic and catabolic actions that maintain tissue homeostasis.
      A number of hormones, cytokines growth factors, and the proximity of various
      cells to bone surfaces influence this process. Inflammatory changes at the bone
      microenvironment result in alterations leading to both excessive bone loss and
      bone formation. Detailed understanding of the physiological and pathological
      mechanisms that dictate these changes will allow us to harness inflammatory
      signals in bone regeneration. RECENT FINDINGS: Recent reports have suggested that
      inflammatory signals are able to stimulate transcription factors that regulate
      osteoblast differentiation from their precursors. SUMMARY: In this review, we
      summarized current understanding of the roles of inflammation in bone resorption
      and bone formation, which give rise to different disorders and discuss the huge
      potential of harnessing these inflammatory signals to achieve bone regeneration.

PMID- 29016374
TI  - Triggers.

PMID- 29016373
TI  - Cancer Yield of Incidental Breast Lesions Detected on Chest Computed Tomography.
AB  - OBJECTIVE: This study aimed to determine the cancer yield for abnormal breast
      findings initially identified on chest computed tomography (CT). MATERIALS AND
      METHODS: This institutional review board-approved, Health Insurance Portability
      and Accountability Act-compliant study retrospectively reviewed reports of 41,217
      consecutive chest CT examinations done from January 1, 2006, to December 31,
      2011, to identify those with breast findings noted in the impression of the
      report. Examinations done for staging of newly diagnosed breast cancer were
      excluded. The electronic medical record was searched for any subsequent breast
      imaging and any corresponding pathology results. Cancer yield was calculated.
      RESULTS: A total of 258 chest CT examinations with abnormal breast findings were
      identified in 218 unique patients. Average patient age was 65.6 years (range, 30
      100 years). There were 207 women and 11 men. Of these, 75 patients had follow-up
      breast imaging in our system. One hundred forty-three patients did not have
      follow-up in our system and were excluded for purposes of cancer detection rate
      calculation. Thirteen of 75 patients were found to have lesions that were
      malignant: infiltrating ductal carcinoma (8), invasive lobular carcinoma (2),
      lymphoma (2), and intracystic papillary cancer with atypical features (1). Four
      of 75 patients underwent further workup and were found to have lesions that were
      benign: fibroadenoma (3) and benign fibrocystic change (1). The remainder of the
      58 of 75 patients had dedicated breast imaging that was classified as either
      Breast Imaging Reporting and Data System score 1 or 2, and no further workup was
      performed. Cancer yield from CT findings was 17.3%. CONCLUSIONS: Abnormal CT
      findings in the breast warrant additional evaluation with dedicated breast
      imaging to evaluate for a possible underlying malignancy. Cancer yield from CT
      findings in this study was 17.3%.

PMID- 29016376
TI  - Possible Psychosis Associated With Buprenorphine Withdrawal.

PMID- 29016377
TI  - Psychopharmacology Training for Psychiatry Residents: A Pilot Iterative Quality
      Improvement Project.

PMID- 29016375
TI  - The Impact of Medication Anticholinergic Burden on Cognitive Performance in
      People With Schizophrenia.
AB  - BACKGROUND: Cognitive deficits are prevalent in people with schizophrenia and
      associated with functional impairments. In addition to antipsychotics,
      pharmacotherapy in schizophrenia often includes other psychotropics, and some of
      these agents possess anticholinergic properties, which may impair cognition. The
      objective of this study was to explore the association between medication
      anticholinergic burden and cognition in schizophrenia. METHODS: Seven hundred
      five individuals with schizophrenia completed a neuropsychological battery
      comprising Judgment of Line Orientation Test, Wechsler Abbreviated Scale of
      Intelligence Matrix Reasoning, Continuous Performance Test-Identical Pairs
      Version, and the Brief Assessment of Cognition in Schizophrenia. Cognitive g and
      3 cognitive factor scores that include executive function, memory/fluency, and
      speed of processing/vigilance, which were derived from a previously published
      analysis, were entered as cognitive variables. Anticholinergic burden was
      computed using 2 anticholinergic scales: Anticholinergic Burden Scale and
      Anticholinergic Drug Scale. Duration and severity of illness, antipsychotic dose,
      smoking status, age, and sex were included as covariates. RESULTS:
      Anticholinergic burden was associated with poorer cognitive performance in
      cognitive g, all 3 cognitive domains and most cognitive tasks in multivariate
      analyses. The associations were statistically significant, but the effect sizes
      were small (for Anticholinergic Burden Scale, Cohen f = 0.008; for
      Anticholinergic Drug Scale, Cohen f = 0.017). CONCLUSIONS: Although our results
      showed a statistically significant association between medications with
      anticholinergic properties and cognition in people with schizophrenia, the impact
      is of doubtful or minimal clinical significance.

PMID- 29016378
TI  - Synchrony and the Art of Mechanical Ventilation.

PMID- 29016380
TI  - Comparison of del Nido Cardioplegia With Blood Cardioplegia in Adult Combined
      Surgery.
AB  - OBJECTIVE: del Nido solution (DNS) is a single-dose cardioplegia designed for
      pediatric use proposed to offer superior myocardial protection in adults.
      However, few data support this claim. We hypothesized that DNS and modified blood
      cardioplegia solution (BS) provide equivalent safety in combined adult valve
      surgery. METHODS: Between November 2014 and December 2015, 25 patients underwent
      primary aortic valve replacement and concomitant coronary artery bypass grafting
      (CABG) with DNS. Outcomes were compared with 25 patients who underwent the same
      surgery with BS between September 2013 and August 2015. RESULTS: All preoperative
      characteristics, comorbidities, and number of CABG performed were similar between
      groups. One hospital death occurred in the BS group. Postoperative creatine
      kinase, MB isotype (16.7 +/- 5.3 MUg/L vs. 22.1 +/- 8.9 MUg/L, P = 0.011) and
      troponin T levels (260 +/- 105.3 ng/L vs. 370.5 +/- 218.4 ng/L, P = 0.028) were
      significantly lower in the DNS group. There was no difference in inotropic or
      vasoactive agent use (P = 0.512). Cardiopulmonary bypass times (65.5 +/- 12.5 min
      vs. 76.6 +/- 19.1 min, P = 0.019) and cross-clamp times (55.6 +/- 11.2 min vs.
      64.3 +/- 18.9 min, P = 0.05) were lower in the DNS group but total operating room
      times (P = 0.198) were similar. Peak postoperative creatinine levels were similar
      in both groups (P = 0.063). There was no difference in postoperative outcomes
      including acute renal failure (P > 0.999), atrial fibrillation (P = 0.773), acute
      respiratory failure (P > 0.999), nor stroke or transient ischemic attack (P >
      0.999). Intensive care unit stay (P = 0.213) and hospital stay (P = 0.1) did not
      differ between groups. CONCLUSIONS: The DNS can be used as an alternative to BS
      in adult concomitant aortic valve replacement + CABG surgery. This supports our
      hypothesis that in this specific setting, DNS provides comparable myocardial
      protection as BS, with possibly shorter cardiopulmonary bypass and cross-clamp
      times.

PMID- 29016382
TI  - Myocardial bridging in left main coronary artery.

PMID- 29016381
TI  - Randomized Study Comparing the Effect of Carbon Dioxide Insufflation on Veins
      Using 2 Types of Endoscopic and Open Vein Harvesting.
AB  - OBJECTIVE: The aim of the study was to assess whether the use of carbon dioxide
      insufflation has any impact on integrity of long saphenous vein comparing 2 types
      of endoscopic vein harvesting and traditional open vein harvesting. METHODS: A
      total of 301 patients were prospectively randomized into 3 groups. Group 1
      control arm of open vein harvesting (n = 101), group 2 closed tunnel (carbon
      dioxide) endoscopic vein harvesting (n = 100) and Group 3 open tunnel (carbon
      dioxide) endoscopic vein harvesting (open tunnel endoscopic vein harvesting) (n =
      100). Each group was assessed to determine the systemic level of partial arterial
      carbon dioxide, end-tidal carbon dioxide, and pH. Three blood samples were
      obtained at baseline, 10 minutes after start of endoscopic vein harvesting, and
      10 minutes after the vein was retrieved. Vein samples were taken immediately
      after vein harvesting without further surgical handling to measure the
      histological level of endothelial damage. A modified validated endothelial
      scoring system was used to compare the extent of endothelial stretching and
      detachment. RESULTS: The level of end-tidal carbon dioxide was maintained in the
      open tunnel endoscopic vein harvesting and open vein harvesting groups but
      increased significantly in the closed tunnel endoscopic vein harvesting group (P
      = 0.451, P = 0.385, and P < 0.001). Interestingly, partial arterial carbon
      dioxide also did not differ over time in the open tunnel endoscopic vein
      harvesting group (P = 0.241), whereas partial arterial carbon dioxide reduced
      significantly over time in the open vein harvesting group (P = 0.001). A profound
      increase in partial arterial carbon dioxide was observed in the closed tunnel
      endoscopic vein harvesting group (P < 0.001). Consistent with these patterns,
      only the closed tunnel endoscopic vein harvesting group demonstrated a sudden
      drop in pH over time (P < 0.001), whereas pH remained stable for both open tunnel
      endoscopic vein harvesting and open vein harvesting groups (P = 0.105 and P =
      0.869, respectively). Endothelial integrity was better preserved in the open vein
      harvesting group compared with open tunnel endoscopic vein harvesting or closed
      tunnel endoscopic vein harvesting groups (P = 0.012) and was not affected by
      changes in carbon dioxide or low pH. Significantly greater stretching of the
      endothelium was observed in the open tunnel endoscopic open tunnel endoscopic
      vein harvesting group compared with the other groups (P = 0.003). CONCLUSIONS:
      This study demonstrated that the different vein harvesting techniques impact on
      endothelial integrity; however, this does not seem to be related to the increase
      in systemic absorption of carbon dioxide or to the pressurized endoscopic tunnel.
      The open tunnel endoscopic harvesting technique vein had more endothelial
      stretching compared with the closed tunnel endoscopic technique; this may be due
      to manual dissection of the vein. Further research is required to evaluate the
      long-term clinical outcome of these vein grafts.

PMID- 29016379
TI  - Oxidative Stress, Inflammation, and Neuroprogression in Chronic PTSD.
AB  - Posttraumatic stress disorder is a serious and often disabling syndrome that
      develops in response to a traumatic event. Many individuals who initially develop
      the disorder go on to experience a chronic form of the condition that in some
      cases can last for many years. Among these patients, psychiatric and medical
      comorbidities are common, including early onset of age-related conditions such as
      chronic pain, cardiometabolic disease, neurocognitive disorders, and dementia.
      The hallmark symptoms of posttraumatic stress-recurrent sensory-memory
      reexperiencing of the trauma(s)-are associated with concomitant activations of
      threat- and stress-related neurobiological pathways that occur against a tonic
      backdrop of sleep disturbance and heightened physiological arousal. Emerging
      evidence suggests that the molecular consequences of this stress-perpetuating
      syndrome include elevated systemic levels of oxidative stress and inflammation.
      In this article we review evidence for the involvement of oxidative stress and
      inflammation in chronic PTSD and the neurobiological consequences of these
      processes, including accelerated cellular aging and neuroprogression. Our aim is
      to update and expand upon previous reviews of this rapidly developing literature
      and to discuss magnetic resonance spectroscopy as an imaging technology uniquely
      suited to measuring oxidative stress and inflammatory markers in vivo. Finally,
      we highlight future directions for research and avenues for the development of
      novel therapeutics targeting oxidative stress and inflammation in patients with
      PTSD.

PMID- 29016384
TI  - Lumen Apposing Metal Stents (LAMSs) for Drainage of Pancreatic and Gallbladder
      Collections: A Meta-analysis.
AB  - BACKGROUND AND AIMS: Endoscopic ultrasound-guided transmural drainage using lumen
      apposing metal stents (LAMSs) is becoming a popular and promising therapeutic
      approach for drainage of intra-abdominal fluid collections. There has been an
      increasing number of studies evaluating LAMS for drainage of pancreatic
      pseudocysts (PP), walled-off pancreatic necrosis (WOPN), and gallbladder (GB)
      drainage. The aim of this meta-analysis is to analyze the literature to date
      regarding the clinical success, technical success, and adverse events of LAMS in
      treatment of pancreatic fluid collections and GB drainage. METHODS: A
      comprehensive search of multiple literature databases through November 2016 was
      performed. Human studies with at least 10 subjects that examined the clinical
      success, technical success, and adverse events of LAMS in treating PP, WOPN, and
      GB drainage were included. RESULTS: A total of 993 patients (608-WOPN; 204-PP;
      181-GB drainage) underwent drainage from 20 trials. For drainage of WOPN, the
      pooled technical success was 98.9% [95% confidence interval (CI): 98.2% to 99.7%]
      and clinical success was 90% (95% CI: 87% to 93%) (tau=0.001). For drainage of
      PP, the pooled technical success was 97% (95% CI: 95% to 99%) and clinical
      success was 98% (95% CI: 96% to 100%), (tau=0.001). For GB drainage, the pooled
      technical success was 95% (95% CI: 91% to 99%) and clinical success was 93% (95%
      CI: 90% to 97%), (tau=0.001). Total adverse events occurred in 11% of patients
      with higher complication rates observed in GB drainage. There was no evidence of
      publication bias in this meta-analysis. CONCLUSIONS: Endoscopic ultrasound-guided
      transmural drainage using LAMS is becoming a widely accepted therapeutic approach
      for the treatment of PP, WOPN, and GB drainage with high clinical and technical
      success rates and acceptable adverse events. Further prospective randomized
      trials reporting long-term clinical efficacy and cost-effectiveness are needed to
      validate LAMS as a therapeutic modality for pancreatic and GB collections.

PMID- 29016385
TI  - A history into genetic and epigenetic evolution of food tolerance: how humanity
      rapidly evolved by drinking milk and eating wheat.
AB  - PURPOSE OF REVIEW: Human exposure to wheat and milk is almost global worldwide.
      Yet the introduction of milk and wheat is very recent (5000-10 000 years) when
      compared to the human evolution. The last 4 decades have seen a rise in food
      allergy and food intolerance to milk and wheat. Often described as
      plurifactorial, the cause of allergic diseases is the result from an interplay
      between genetic predisposition and epigenetic in the context of environmental
      changes. RECENT FINDINGS: Genetic and epigenetic understanding and their
      contribution to allergy or other antigen-driven diseases have considerably
      advanced in the last few years. Yet, environmental factors are also quite
      difficult to identify and associate with disease risk. Can we rethink our old
      findings and learn from human history and recent genetic studies? SUMMARY: More
      than one million years separate Homo habilis to today's mankind, more than 1
      million years to develop abilities to obtain food by foraging in diverse
      environments. One million year to adjust and fine-tune our genetic code and
      adapt; and only 1% of this time, 10 000 years, to face the three biggest
      revolutions of the human kind: the agricultural revolution, the industrial
      revolution and the postindustrial revolution. With big and rapid environmental
      changes come adaptation but with no time for fine-tuning. Today tolerance and
      adverse reactions to food may be a testimony of adaptation successes and
      mistakes.

PMID- 29016383
TI  - Pathogenesis of Neisseria gonorrhoeae in the female reproductive tract:
      neutrophilic host response, sustained infection, and clinical sequelae.
AB  - PURPOSE OF REVIEW: Gonorrhea is a major global health concern, caused by the
      bacterium Neisseria gonorrhoeae. The main clinical feature of acute gonorrhea is
      neutrophilic influx that is unable to clear infection. Women of reproductive age
      are predominantly at risk for serious sequelae of gonorrhea, including pelvic
      inflammatory disease, ectopic pregnancy, and infertility. This review will
      highlight how neutrophils are recruited to the female reproductive tract (FRT) in
      response to N. gonorrhoeae, how N. gonorrhoeae resists killing by neutrophils,
      and the connection between neutrophilic inflammation and cellular damage. RECENT
      FINDINGS: Epithelial cells and immune cells of the FRT recognize and respond to
      N. gonorrhoeae lipid A and heptose bisphosphate of lipooligosaccharide, porin,
      lipoproteins, and peptidoglycan fragments. N. gonorrhoeae skews the resulting
      immune response toward a neutrophilic, Th17-like response. N. gonorrhoeae has
      multiple, nonredundant mechanisms to survive inside neutrophils and in neutrophil
      extracellular traps. Infection that ascends to the upper FRT induces the further
      release of inflammatory cytokines and matrix metalloproteinases, which cause
      epithelial damage. SUMMARY: N. gonorrhoeae is remarkable in its ability to
      recruit neutrophils, yet survive in their midst. New models being developed for
      FRT infection with N. gonorrhoeae will be useful to reveal the mechanisms
      underlying these observations.

PMID- 29016386
TI  - Primary malignant melanoma arising in an ovarian cystic teratoma.
AB  - Primary malignant melanoma arising in an ovarian cystic teratoma is exceedingly
      rare event with an estimated incidence of 0.2-0.8%. So far, there have been
      approximately only 47 relevant reports. We report a case of primary malignant
      melanoma of the ovary arising in a cystic teratoma here. Moreover, we review
      systematically the disease from the following aspects, that origin, clinical
      characteristics, accessory examination, pathological features, diagnosis,
      differential diagnosis, treatment, prognosis.

PMID- 29016388
TI  - The Relationship Between Posttraumatic Stress Disorder and Chronic Pain in People
      Seeking Treatment for Chronic Pain: The Mediating Role of Psychological
      Flexibility.
AB  - OBJECTIVES: The symptoms of posttraumatic stress disorder (PTSD) and chronic pain
      are thought to interact to increase the severity and impact of both conditions,
      but the mechanisms by which they interact remain unclear. This study examines the
      relationship between PTSD and chronic pain and whether indices of Psychological
      Flexibility mediate the relationship between these 2 conditions. MATERIALS AND
      METHODS: Standardized self-report measures of PTSD, pain severity, pain
      interference, depression, and psychological flexibility (pain-related acceptance,
      committed action, cognitive fusion, and values-based action) were obtained from
      315 people seeking treatment for chronic pain who also reported at least 1
      traumatic experience. RESULTS: People seeking treatment for chronic pain and
      reporting symptoms consistent with a current diagnosis of PTSD had significantly
      higher levels of pain severity, pain interference, depression, and cognitive
      fusion and lower levels of pain-related acceptance and committed action than
      those reporting symptoms below the diagnostic threshold for PTSD. Pain-related
      acceptance, committed action, cognitive fusion, and depression mediated the
      relationship between PTSD and pain severity/interference, with pain-related
      acceptance being the strongest mediator from the Psychological Flexibility model.
      DISCUSSION: Processes from the Psychological Flexibility model were identified as
      mediators of the relationship between PTSD and chronic pain in people seeking
      treatment for chronic pain. The Psychological Flexibility model may be useful as
      an overarching model to help understand the relationship between PTSD and chronic
      pain. It is possible that targeting pain-related acceptance, committed action,
      and cognitive fusion (among other processes) in the treatment of chronic pain may
      produce corresponding improvements in comorbid symptoms of PTSD when these are
      present and may reduce impacts of PTSD on outcomes of chronic pain. Conversely,
      targeting of these processes in the treatment of PTSD may produce similar
      improvements for symptoms of chronic pain. Further research to evaluate these
      possibilities is needed.

PMID- 29016387
TI  - Lymphocyte-to-monocyte ratio is associated with survival in pembrolizumab-treated
      metastatic melanoma patients.
AB  - The peripheral blood lymphocyte-to-monocyte ratio (LMR) has been associated with
      prognosis in many malignancies including metastatic melanoma. However, it has not
      been studied in patients treated with immune checkpoint inhibitors. In this
      study, we analyzed the baseline LMR with progression-free survival (PFS) and
      overall survival (OS) in metastatic melanoma patients treated with pembrolizumab.
      A total of 133 patients with metastatic melanoma treated with pembrolizumab were
      included in this retrospective study. LMR was calculated from pretherapy
      peripheral blood counts and the optimal cutoff value was determined by a receiver
      operator characteristic curve. PFS and OS were evaluated using the Kaplan-Meier
      method and multivariate Cox proportional hazard modeling. Patients with an LMR of
      at least 1.7 showed improved PFS (hazard ratio=0.55; 95% confidence interval:
      0.34-0.92; P=0.024) and OS (hazard ratio=0.29; 95% confidence interval: 0.15
      0.59; P=0.0007). The baseline LMR is associated with PFS and OS in metastatic
      melanoma patients treated with pembrolizumab, and could represent a convenient
      and cost-effective prognostic biomarker. Validation of these findings in an
      independent cohort is needed.

PMID- 29016389
TI  - Do Changes in Sensory Processing Precede Low Back Pain Development in Healthy
      Individuals?
AB  - OBJECTIVES: Low back pain (LBP) is the most commonly reported chronic pain
      condition. In this study, a clinically relevant, induced-LBP paradigm was used to
      study sensory processing as a risk factor and predictor for LBP development in
      healthy people. Our aim was to examine sensory processing in those who do develop
      LBP and those who do not develop LBP with the paradigm, and to examine the
      relationships between scores on psychosocial questionnaires and sensory
      processing measures in these healthy people. METHODS: A total of 71 participants
      completed the Pain Catastrophizing Scale (PCS) and Hospital Anxiety and
      Depression Scale (HADS) and then took part in quantitative sensory testing. An
      induced-LBP paradigm, where participants stand for 2 hours and rate their low
      back symptoms over time, was used to classify participants as those who did
      develop LBP and those who did not develop LBP. RESULTS: No differences in sensory
      processing were identified between those who did develop LBP and those who did
      not develop LBP (Ps>0.05). Scores for the PCS and HADS were similar between the
      groups (Ps>0.05). Small significant relationships between PCS scores and cold
      detection and cold pain thresholds were found (rs=0.23 to 0.31; Ps<0.05) and
      between the pressure pain thresholds at the thenar eminence and paraspinals
      (r=0.53; P<0.01). DISCUSSION: These results provide evidence that altered sensory
      processing was not present in healthy people and thus is not a risk factor for
      development of LBP in standing.

PMID- 29016390
TI  - Response: Prescription Opioid Use and the Risk of Disability.

PMID- 29016391
TI  - Perioperative and Long-term Outcome of the Warshaw Technique in Laparoscopic
      Spleen-preserving Distal Pancreatectomy.
AB  - PURPOSE: The purpose of this study was to compare the safety and outcomes of
      laparoscopic splenic vessel preservation (Lap-SVP) to those of laparoscopic
      Warshaw technique (Lap-WT). MATERIALS AND METHODS: Fourteen patients underwent
      Lap-SVP and 5 patients underwent Lap-WT. Their clinical data and outcomes of the
      2 procedures were compared. RESULTS: The operative time, intraoperative blood
      loss, clinically relevant pancreatic fistula, and the rate of splenic infarction
      were significantly higher in the patients who underwent Lap-WT than in those who
      underwent Lap-SVP. In both groups, the platelet count ratio and splenic volume
      ratio at 1 month after the operation did not differ from the preoperative values.
      Two patients in the Lap-WT group experienced splenic infarction, and could be
      observed without any treatment. CONCLUSIONS: The long-term outcome of Lap-WT was
      relevant. Therefore, Lap-WT could be a treatment option for patients who may not
      have undergone Lap-SVP.

PMID- 29016393
TI  - Biomechanical Implications of Training Volume and Intensity in Aging Runners.
AB  - : Running speed is slower in middle-age compared with younger runners due to
      reduced ankle but not hip and knee kinetic output. Running-specific training
      helps attenuate age-related declines in measures of endurance, muscle strength,
      and gait speed. Considering the adaptability of the human body in response to
      imposed stresses, maintaining training volume and intensity may play a role in
      modifying running biomechanics in middle-age runners. PURPOSE: To compare running
      biomechanics between young and middle-age runners when controlling for the
      confounding effects of training volume and intensity. METHODS: Fifteen middle-age
      runners, 15 young runners with similar training volume as the middle-age group
      and, 15 young runners with similar preferred training paces (i.e., intensity) as
      the middle-age runners participated in the study. Lower-limb joint kinetics were
      calculated from kinematic and ground reaction force data during overground
      running at a submaximal speed and compared among groups. RESULTS: Middle-age
      runners ran with similar peak ankle power compared with volume-matched younger
      runners although peak plantarflexor moment was 10.5% lower in the middle age
      group (P = 0.046; Cohen d = 0.78). Middle-age runners ran with similar ankle
      plantarflexor moment and joint power compared with training pace-matched young
      runners. As expected, no age-related differences were observed in hip and knee
      kinetics when training volume or pace were matched between age groups. These
      results suggest that training pace may be more effective in attenuating age
      related declines in plantarflexor kinetics in middle-age runners. CONCLUSIONS:
      From these findings, we propose the hypothesis that both training volume and
      training pace may play a role in maintaining plantarflexor kinetics but that
      training pace may have a greater impact on ankle plantarflexor kinetics in middle
      age runners.

PMID- 29016392
TI  - Increased Walking's Additive and No Substitution Effect on Total Physical
      Activity.
AB  - PURPOSE: We assessed the associations between a change in time spent walking and
      a change in total physical activity (PA) time within an urban living adult sample
      to test for additive or substitution effects. METHODS: Participants living in the
      greater Seattle area were assessed in 2008-2009 and again 1-2 yr later (2010
      2011). At each time point, they wore accelerometers and GPS units and recorded
      trips and locations in a travel diary for seven consecutive days. These data
      streams were combined to derive a more objective estimate of walking and total
      PA. Participants also completed the International Physical Activity Questionnaire
      to provide self-reported estimates of walking and total PA. Regression analyses
      assessed the associations between within-participant changes in objective and
      self-reported walking and total PA. RESULTS: Data came from 437 participants. On
      average, a 1-min increase in total walking was associated with an increase in
      total PA of 1 min, measured by objective data, and 1.2-min, measured by self
      reported data. A similar additive effect was consistently found with utilitarian,
      transportation, or job-related walking, measured by both objective and self
      reported data. For recreational walking, the effect of change was mixed between
      objective and self-reported results. CONCLUSION: Both objective and self-reported
      data confirmed an additive effect of utilitarian and total walking on PA.

PMID- 29016394
TI  - miR-20b/106a modulate Ngn2 gene expression during neural differentiation of human
      umbilical cord mesenchymal stem cells.
AB  - The aim of this study was to perform neural differentiation of mesenchymal stem
      cells derived from Wharton's jelly of human umbilical cord (HUMSCs) and explore
      the role of miR-20b and miR-106a, which may regulate Neurogenin-2 (Ngn2)
      expression during the neural differentiation. HUMSCs were cultured and induced in
      vitro. The cells were stained for nestin and microtubule-associated protein 2
      (MAP2) by immunofluorescence. The interactional binding sites between the 3'
      untranslated region (3'-UTR) of Ngn2 mRNA and miR-20b or miR-106a were predicted
      by bioinformatics and identified by a dual-luciferase assay. The expressions of
      Ngn2, miR-20b, and miR-106a were determined by real-time PCR and western blot
      before and after the neural differentiation. After infection of miR-20b or miR
      106a, the expressions of Ngn2, MAP2, and beta III-tubulin (TUBB3) were measured.
      HUMSCs showed a uniform pattern with a typical short spindle-shaped morphology.
      Fourteen days after neural differentiation, HUMSCs showed neuronal traits of
      pyramidal appearance. TargetScan and miRanda showed that miR-20b and miR-106a
      were well complementary with Ngn2 3'-UTR. Identified by the dual-luciferase
      assay, we found that miR-20b and miR-106a inhibit Ngn2 expression by binding to
      its 3'-UTR. Furthermore, the expression of Ngn2 mRNA was almost reciprocal to
      that of miR-20b and miR-106a by real-time PCR during the neural differentiation
      of HUMSCs. Overexpression of miR-20b and miR-106a downregulated the expressions
      of Ngn2, MAP2, and TUBB3. miR-20b and miR-106a may directly or indirectly
      regulate neuronal genes expression to modulate the neural differentiation of
      HUMSCs.

PMID- 29016396
TI  - State Variation in Quality Outcomes and Disparities in Outcomes in Community
      Health Centers.
AB  - BACKGROUND: Prior studies have reported that community health centers perform as
      well as other sites of care, despite serving more vulnerable patient populations.
      However, there is little prior study of geographic variation in quality outcomes
      and disparities in outcomes in this setting. Quantifying geographic variation is
      important so as to target quality improvement efforts and funding and to learn
      from states where total quality is highest and racial/ethnic disparities are
      lowest. OBJECTIVES: To estimate between-state variation in hypertension,
      diabetes, and pregnancy outcomes and racial/ethnic disparities in these outcomes
      for health center patients. METHODS: Using data on all US health centers from
      2010 to 2014 (N=1047 health centers/year, or 21.2 million patients in 2014), we
      used linear regression models to estimate adjusted quality outcomes and
      racial/ethnic disparities in quality outcomes by state for hypertension control,
      diabetes control, and normal birthweight. RESULTS: We found wide variation in
      both outcomes and racial/ethnic disparities in outcomes between states for
      patients seen at health centers. For instance, between states, the mean
      proportion of patients with hypertension control ranged from 58% to 70% for white
      patients, from 49% to 64% for black patients, and from 53% to 74% for Hispanic
      patients (P<0.001). Racial/ethnic disparities in outcomes ranged from negative or
      nonsignificant in some states to positive in others. CONCLUSIONS: Wide variation
      in health center patient outcomes and disparities in outcomes is observed between
      states. This variation suggests that policymakers should target funding and
      interventions to underperforming states, and identify determinants of high
      quality in higher performing states.

PMID- 29016395
TI  - Neighborhood Socioeconomic Status Predicts Health After Hospitalization for Acute
      Coronary Syndromes: Findings From TRACE-CORE (Transitions, Risks, and Actions in
      Coronary Events-Center for Outcomes Research and Education).
AB  - OBJECTIVE: To explore the influence of contextual factors on health-related
      quality of life (HRQoL), which is sometimes used as an indicator of quality of
      care, we examined the association of neighborhood socioeconomic status (NSES) and
      trajectories of HRQoL after hospitalization for acute coronary syndromes (ACS).
      METHODS: We studied 1481 patients hospitalized with acute coronary syndromes in
      Massachusetts and Georgia querying HRQoL via the mental and physical components
      of the 36-item short-form health survey (SF-36) (MCS and PCS) and the physical
      limitations and angina-related HRQoL subscales of the Seattle Angina
      Questionnaire (SAQ) during hospitalization and at 1-, 3-, and 6-month
      postdischarge. We categorized participants by tertiles of the neighborhood
      deprivation index (a residence-census tract-based measure) to examine the
      association of NSES with trajectories of HRQoL after adjusting for individual
      socioeconomic status (SES) and clinical characteristics. RESULTS: Participants
      had mean age 61.3 (SD, 11.4) years; 33% were female; 76%, non-Hispanic white;
      11.2% had household income below the federal poverty level. During 6 months
      postdischarge, living in lower NSES neighborhoods was associated with lower mean
      PCS scores (1.5 points for intermediate NSES; 1.8 for low) and SAQ scores (2.4
      and 4.2 points) versus living in high NSES neighborhoods. NSES was more
      consequential for patients with lower individual SES. Individuals living below
      the federal poverty level had lower average MCS and SAQ physical scores (3.7 and
      7.7 points, respectively) than those above. CONCLUSIONS: Neighborhood deprivation
      was associated with worse health status. Using HRQoL to assess quality of care
      without accounting for individual SES and NSES may unfairly penalize safety-net
      hospitals.

PMID- 29016398
TI  - Low-Intensity Pulsed Ultrasound Stimulation for Tendon-Bone Healing: A Dose
      Dependent Study.
AB  - OBJECTIVE: The aim of the study was to evaluate the dosage effect of low
      intensity pulsed ultrasound stimulation on tendon-bone healing. DESIGN: Standard
      partial patellectomies were performed on 120 mature New Zealand rabbits randomly
      assigned into the following three groups: a control group (daily mock sonication,
      20 mins), a qd group (daily ultrasonication, 20 mins), and a bid group
      (ultrasonication twice a day, 20 mins each time). The rabbits were killed 8 or 16
      wks postoperatively, and the microarchitectural, histological, and mechanical
      properties of the patella-patellar tendon interface were evaluated. RESULTS:
      Microcomputed tomography analysis showed that the bid group exhibited more new
      bone formation and mineralization than the other groups in the tendon-bone
      healing position at both 8 and 16 wks postoperatively. Histological assessments
      confirmed that the bid group exhibited a significantly better patella-patellar
      tendon interface than the other groups, as shown by the increased formation and
      remodeling of newly formed bone and a fibrocartilage layer. The biomechanical
      properties of the regenerated patella-patellar tendon interface significantly
      improved in the bid group. CONCLUSIONS: Low-intensity pulsed ultrasound
      stimulation treatment twice a day was more effective than the once-a-day
      treatment on tendon-bone healing.

PMID- 29016397
TI  - Feasibility and Reliability of Functional Muscle Tests in Lung Transplant
      Recipients.
AB  - OBJECTIVE: This study investigates the feasibility, reliability, and correlations
      of recommended functional tests in lung transplant recipients shortly after
      surgery. DESIGN: This is an observational study. METHODS: Fifty patients (28
      females) performed well-standardized maximum isometric back extension in a
      sitting position, handgrip strength, and Biering-Sorensen endurance tests shortly
      before discharge from the acute hospital, shortly thereafter, and 2 mos later
      after subacute rehabilitation. RESULTS: Back extension testing was well feasible,
      but only two thirds of the patients could perform the Biering-Sorensen test at
      baseline and they experienced a greater number of minor but no major adverse
      events. Absolute reliability measures and the intraclass correlation coefficients
      were excellent for the strength (0.97-0.98 [0.95-0.99]) and good for the
      endurance tests (0.69 [0.26-0.87]). Handgrip revealed high correlation with back
      strength (>=0.75) but not with Biering-Sorensen scores. CONCLUSIONS: Well
      controlled maximum back strength testing is feasible and reliable, and the scores
      are highly correlated with grip strength in lung transplant recipients shortly
      before hospital discharge. The Biering-Sorensen test should be limited to
      patients without dominant weakness and/or fear. Future research should
      investigate whether grip instead of back extension strength can safely be used
      for proper exercise prescription.

PMID- 29016399
TI  - Heart-Shaped Sign: A Rare Stroke Syndrome.

PMID- 29016400
TI  - Alterations in the Mechanical Response of Deep Dorsal Neck Muscles in Individuals
      Experiencing Whiplash-Associated Disorders Compared to Healthy Controls: An
      Ultrasound Study.
AB  - OBJECTIVE: The aim of this study was to investigate and compare the mechanical
      responses of dorsal neck muscles in individuals with whiplash-associated
      disorders (WAD) versus healthy individuals. DESIGN: This study included 36
      individuals with WAD (26 women and 10 men) and 36 healthy controls (26 women and
      10 men). Ultrasound imaging with speckle tracking was used to measure deformation
      and deformation rate in five dorsal neck muscles during a neck extension task.
      RESULTS: Compared with controls, individuals with WAD showed higher deformations
      of the semispinalis cervicis (P = 0.02) and multifidus (P = 0.002) muscles and
      higher deformation rates (P = 0.03 and 0.0001, respectively). Among individuals
      with WAD, multifidus deformation and deformation rate were significantly
      associated with pain, disability, and fatigue (r = 0.31-0.46, P = 0.0001-0.01).
      CONCLUSIONS: These findings indicate that the mechanical responses of the deep
      dorsal neck muscles differ between individuals with WAD and healthy controls,
      possibly reflecting that these muscles use altered strategies while performing a
      neck extension task. This finding provides new insight into neck muscles
      pathology in patients with chronic WAD and may help improve rehabilitation
      programs. TO CLAIM CME CREDITS: Complete the self-assessment activity and
      evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon
      completion of this article, the reader should be able to: (1) Summarize the
      mechanical responses of dorsal neck muscles during loading of the neck muscles
      via an extension task in individuals with chronic whiplash associated disorders
      and healthy volunteers; (2) Differentiate mechanical responses between five
      dorsal neck muscles while loading the neck via an extension task; and (3)
      Describe the relationships between the mechanical responses of the dorsal neck
      muscles with the patients' perception of neck pain, disability, and fatigue.
      LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is
      accredited by the Accreditation Council for Continuing Medical Education to
      provide continuing medical education for physicians.The Association of Academic
      Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA
      PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with
      the extent of their participation in the activity.

PMID- 29016401
TI  - Evaluation of the Effectiveness of Neuromuscular Electrical Stimulation After
      Total Knee Arthroplasty: A Meta-Analysis.
AB  - OBJECTIVE: The aim of the study was to evaluate the efficacy of the use of the
      neuromuscular electrical stimulation after total knee arthroplasty. DESIGN: The
      study used a systematic review of randomized controlled trials (MEDLINE, PubMed,
      Cochrane Library, and PEDro) using Patient Population or Problem, Intervention,
      Comparison, Outcomes, Setting approach to formulate the research question,
      controlled terms, and Boolean operators. Inclusion and exclusion criteria were
      defined in advance. "Neuromuscular electrical stimulation" and "total knee
      arthroplasty" were used as keywords. The overall risk of bias was determined
      according to the following: random sequence generation, concealment, blinding
      mass of participants and staff, commissioning blind assessment results,
      incomplete data, and loans received. RESULTS: Of the 36 identified studies, six
      were included in the review (496 participants). In these studies, one group of
      patients followed a rehabilitation protocol (control group) and the other
      followed a rehabilitation program plus a session of neuromuscular electrical
      stimulation (neuromuscular electrical stimulation group). Patients of
      neuromuscular electrical stimulation groups got the best scores (timed up and go
      test, stair climbing test, and walk test). Neuromuscular electrical stimulation
      benefits were strong in the first postoperative weeks/months and gradually
      diminished. CONCLUSIONS: Neuromuscular electrical stimulation allows a slightly
      better functional recovery after total knee arthroplasty, especially in the first
      period, with more evident benefits in patients with a severe lack of muscular
      activation. Nevertheless, there is no difference at medium-long term.

PMID- 29016402
TI  - Disability and Health Consequences of Traumatic Brain Injury: National
      Prevalence.
AB  - OBJECTIVE: The aim of the study was to measure the prevalence of traumatic brain
      injury (TBI)-related disability and health status in the general population.
      DESIGN: The French National Survey, conducted in households and institutions,
      assessed 33,896 adults. Data included sequelae from TBI, impairments, current
      health conditions, and uses of health services. Analyses, adjusted for age and
      sex, compared subjects who declared sequelae from TBI (n = 479) with the
      remaining survey population (n = 33,287). Use of weighting factors ensured that
      results were representative of the national population. RESULTS: Prevalence of
      persistent sequelae from TBI in France was 704/100,000. Median time since injury
      was 14 yrs. For all Core Set items of the International Classification of
      Functioning, subjects with TBI reported more impairments than the control
      population: adjusted odds ratios from 1.7 (behavioral difficulties) to 8.6 (motor
      difficulties). Rates of cardiovascular, respiratory, musculoskeletal, digestive,
      urological, neurological, and psychiatric conditions were higher in the TBI
      population. Use of health services was greater, and women with TBI had higher
      rates of unmet health needs. CONCLUSIONS: Persistent sequelae from TBI
      significantly affect health in the general population. Planning of post-TBI care
      should address the chronic needs of these persons.

PMID- 29016403
TI  - The Influence of Tumor Stage on the Prognostic Value of Ki-67 Index and Mitotic
      Count in Small Intestinal Neuroendocrine Tumors.
AB  - Tumor cell proliferation rate determined by either Ki-67 index or mitotic count
      (MC) has shown to be a prognostic factor for gastrointestinal neuroendocrine
      tumors in general, and after its incorporation in the 2010 World Health
      Organization tumor grading system, it has become essentially mandatory in
      pathology reports for all gastrointestinal neuroendocrine tumors, regardless of
      tumor location. Nevertheless, clinical significance for the Ki-67 index or MC has
      not been well demonstrated in small intestinal neuroendocrine tumor (SINET),
      especially those without distant metastasis, the majority of which have very low
      proliferation rates. We assessed the clinical behavior of 130 SINETs in relation
      to stage, Ki-67 index, MC, and other pathologic features. Most SINETs (86%) were
      grade 1 and 14% were grade 2. There were no grade 3 tumors or poorly
      differentiated neuroendocrine carcinomas. On multivariate analysis, age, Ki-67
      index >5%, MC >10/50 high-power field, stage IV, and liver metastases were
      associated with increased risk of death in all patients. When both stage and
      grade were considered, Ki-67 index >5% was associated with a nearly 4-fold
      increased risk of death in stage IV cases (n=60). In contrast, Ki-67 index did
      not show prognostic value for patients with stages I to III disease (n=70),
      although MC >1/50 high-power field was significantly associated with death on
      multivariable analysis. Our study confirms that liver metastasis and increased
      tumor cell proliferation rate are independent prognostic factors for SINETs, but
      shows that most SINETs have a very low proliferation rate, which limits its value
      for predicting tumor behavior. By combining staging and grading information, we
      demonstrate different roles and cutoff values of Ki-67 index and MC in SINET with
      different stages.

PMID- 29016405
TI  - Definition of Barrett Esophagus in the United States: Support for Retention of a
      Requirement for Goblet Cells.
AB  - Barrett esophagus (BE) predisposes patients to the development of esophageal
      adenocarcinoma (EAC). However, the global definition of BE is controversial.
      Pathologists in Europe and the United States require intestinal metaplasia (IM)
      within columnar-lined mucosa (CLM) in the tubular esophagus to diagnose BE,
      whereas in the UK and Japan only the presence of CLM is required. To aid in
      establishing an appropriate definition for BE, we evaluated whether IM
      accompanies EAC in a US patient cohort. We examined a series of 139 consecutive
      patients who underwent endoscopic mucosal resections or esophagectomies for EAC
      performed at a US tertiary care center. The resection specimens were evaluated
      for the presence (IM+) or absence (IM-) of IM within CLM. Ninety-seven (70%)
      patients were IM+. Tumors found in IM- patients tended to be advanced at the time
      of resection (57% pT3 or greater, IM-; 31% pT3 or greater, IM+; P=0.02) such that
      the tumor may have "overgrown" zones of IM. We hypothesized that changes as a
      result of neoadjuvant chemotherapy or radiation might mask preexisting IM. When
      evaluating this hypothesis, we found that 34 of 39 of treatment-naive patients
      were IM+. Two of the 5 IM- patients had prior IM+ biopsies resulting in 92% of
      treatment-naive patients who were IM+. In our US hospital population, CLM with IM
      in the tubular esophagus is found in association with EAC in 70% to 92% of
      patients. We believe that based on these data the United States definition of BE
      should continue to require the presence of IM.

PMID- 29016404
TI  - Hepatobiliary Mucinous Cystic Neoplasms With Ovarian Type Stroma (So-Called
      "Hepatobiliary Cystadenoma/Cystadenocarcinoma"): Clinicopathologic Analysis of 36
      Cases Illustrates Rarity of Carcinomatous Change.
AB  - The literature is highly conflicting on hepatobiliary mucinous cystic neoplasms
      (MCNs), aka "hepatobiliary cystadenoma/cystadenocarcinoma," largely because
      ovarian stroma (OS) was not a requirement until WHO-2010 and is not widely
      applied even today. In this study, MCNs (with OS) accounted for 24 of 229 (11%)
      resected hepatic cysts in one institution. Eight of the 32 (25%) cysts that had
      been originally designated as hepatobiliary cystadenoma/cystadenocarcinoma at the
      time of diagnosis proved not to have an OS during this review and were thus re
      classified as non-MCN. In total, 36 MCNs (with OS) were analyzed-24 from the
      institutional files and 12 consultation cases. All were women. Mean age was 51
      (28 to 76 y). Mean size was 11 cm (5 to 23 cm). Most (91%) were intrahepatic and
      in the left lobe (72%). Preoperative imaging mentioned "neoplasm" in 14 (47%) and
      carcinoma was a differential in 6 (19%) but only 2 proved to have carcinoma.
      Microscopically, only 47% demonstrated diffuse OS (>75% of the cyst wall/lining);
      OS was often focal. The cyst lining was often composed of non-mucinous biliary
      epithelium, and this was predominant in 50% of the cases. Degenerative changes of
      variable amount were seen in most cases. In situ and invasive carcinoma was seen
      in only 2 cases (6%), both with small invasion (7 and 8 mm). Five cases had
      persistence/recurrence, 2 confirmed operatively (at 7 mo and 15 y). Of the 2
      cases with carcinoma, one had "residual cyst or hematoma" by radiology at 4
      months, and the other was without disease at 3 years. In conclusion, many cysts
      (25%) previously reported as hepatobiliary cystadenoma/cystadenocarcinoma are not
      MCNs. True MCNs are uncommon among resected hepatic cysts (11%), occur
      exclusively in females, are large, mostly intrahepatic and in the left lobe
      (72%). Invasive carcinomas are small and uncommon (6%) compared with their
      pancreatic counterpart (16%). Recurrences are not uncommon following incomplete
      excision.

PMID- 29016406
TI  - Visualization of Immune Responses in the Cornea.
AB  - The eye has become a useful site for the investigation and understanding of local
      and systemic immune responses. The ease of access and transparency of the cornea
      permits direct visualization of ocular structures, blood vessels, and lymphatic
      vessels, allowing for the tracking of normal and pathological biological
      processes in real time. As a window to the immune system, we have used the eye to
      dissect the mechanisms of corneal inflammatory reactions that include innate and
      adaptive immune responses. We have identified that the ocular microenvironment
      regulates these immune responses by recruiting different populations of
      inflammatory cells to the cornea through local production of selected chemokines.
      Moreover, crosstalk between T cells and macrophages is a common and crucial step
      in the development of ocular immune responses to corneal alloantigens. This
      review summarizes the data generated by our group using intravital fluorescent
      confocal microscopy to capture the tempo, magnitude, and function of innate and
      adaptive corneal immune responses.

PMID- 29016407
TI  - A Novel Entity of Corneal Diseases with Irregular Posterior Corneal Surfaces:
      Concept and Clinical Relevance.
AB  - Various corneal diseases, such as hereditary corneal dystrophies, corneal
      infection, and bullous keratopathy, cause corneal opacity, scarring, and edema,
      leading to severely decreased visual acuity and loss of vision. These diseases
      were regarded as corneal opacity diseases, and the decreased visual acuity was
      considered to be predominantly caused by corneal opacity. The influence of
      corneal irregular astigmatism on vision has been poorly understood to date,
      mainly because accurate quantification of irregular astigmatism has been
      technically challenging. We have performed detailed analyses of the corneal
      higher-order aberrations (HOAs) of the anterior and posterior surfaces and total
      cornea in corneal diseases, using an anterior segment imaging system combined
      with a ray-tracing method. Subsequently, we conducted correlation analyses
      between corneal HOAs and visual acuities and characterized the typical HOA
      patterns in the corneal diseases. Our recent studies demonstrated that corneal
      HOAs directly degrade visual acuity in eyes with mild-to-moderate corneal
      opacities, such as corneal dystrophies, corneal scarring, and bullous
      keratopathy. The findings also suggested that correction of corneal HOAs using
      rigid gas-permeable contact lenses is effective in eyes with a smooth posterior
      surface and useful in certain patients with corneal scarring to some extent. Our
      data will be useful for decision making regarding surgical interventions, based
      on the amount of corneal HOAs. Our results further indicate the clinical
      relevance of irregular astigmatism in the posterior surfaces in assessing the
      visual function of eyes with various corneal diseases.

PMID- 29016408
TI  - Family-Initiated Pediatric Rapid Response: Characteristics, Impetus, and
      Outcomes.
AB  - BRIEF DESCRIPTION: Family-initiated rapid response (FIRR) empowers families to
      express concern and seek care from specialized response teams. We studied FIRRs
      that occurred in a pediatric tertiary hospital over a 3-year period. The main
      aims were to describe the characteristics and outcomes of FIRRs and compare them
      with clinician-activated RRs (C-RRs). Of the 1,906 RRs events reviewed, 49 (2.6%)
      were FIRRs. All FIRRs had appropriate clinical triggers with the most common
      being uncontrolled pain. Chronic conditions and previous admissions were present
      in 61%. More than half of FIRRs had a vital sign change that should have
      qualified C-RR activation. Seventy-six percent FIRRs needed at least one or more
      interventions. Twenty-seven percent of FIRRs needed transfer to intensive care
      unit compared with 60% transfer rate for C-RRs. PURPOSE OF SUBMISSION/RELEVANCE
      TO HEALTHCARE QUALITY: Family-initiated rapid response events were activated for
      legitimate concerns and frequently needed clinical interventions. Enhanced
      information and awareness of FIRR can improve utilization of the system and
      enhance family satisfaction, patient safety, and outcomes. Disseminating the
      information on FIRR and the importance of family involvement will improve the
      care of children and empower family members.

PMID- 29016409
TI  - Anterior Ischemic Optic Neuropathy Due to Calciphylaxis.
AB  - A 72-year-old woman experienced anterior ischemic optic neuropathy in her left
      eye. The funduscopic and fluorescein angiographic findings were strongly
      suggestive of giant cell arteritis. Temporal artery biopsy revealed extensive
      calcification in the vessel wall consistent with calciphylaxis. This unusual
      disorder should be considered in the differential diagnosis of anterior ischemic
      optic neuropathy, particularly the arteritic form.

PMID- 29016410
TI  - Type I Dural Arteriovenous Fistula Mimicking Dural Venous Thrombosis-Related
      Intracranial Hypertension.

PMID- 29016411
TI  - Vanishing Act: Gorham-Stout Disease Leading to Dynamic Cerebrospinal Fluid
      Abnormalities.

PMID- 29016412
TI  - False Lung Metastasis: Concurrent Ewing Sarcoma and Minimally Invasive
      Adenocarcinoma.
AB  - Pediatric lung cancer is a very rare occurrence, particularly as a primary
      lesion. A concurrent diagnosis is even more unusual and only reported a handful
      of times in Ewing sarcoma. Our patient is a 13-year-old boy who had concurrent
      diagnoses of Ewing sarcoma and minimally invasive adenocarcinoma of the lung,
      formerly bronchoalveolar carcinoma. To our knowledge this has also been found in
      at least 1 other case. There are some classic genetic mutations associated with
      Ewing sarcoma. None have been found to be linked with the concurrent diagnosis. A
      biological linkage is worth considering.

PMID- 29016413
TI  - Femoral Vein Catheter is an Important Risk Factor for Catheter-related Thrombosis
      in (Near-)term Neonates.
AB  - Central venous catheters (CVCs) in neonates are associated with an increased risk
      of thrombosis. Most reports focus on umbilical venous catheters (UVCs) and
      peripherally inserted central catheters (PICCs), whereas data available on
      femoral venous catheters (FVCs) are limited. We performed a retrospective cohort
      study in all neonates (gestational age >=34 wk) with CVCs. The primary outcome
      was the occurrence of thrombosis in CVCs. The secondary outcomes were possible
      risk factors for thrombosis, the thrombotic incidence in FVCs, UVCs, and PICCs,
      and clinical aspects of thrombosis in these groups. A total of 552 neonates
      received a total of 656 catheters, including 407 (62%) UVCs, 185 (28%) PICCs, and
      64 (10%) FVCs. Thrombosis was detected in 14 cases, yielding an overall incidence
      of 2.1% or 3.6 events per 1000 catheter days. FVC was significantly associated
      with the occurrence of thrombosis when compared with UVC (P=0.02; odds ratio,
      3.8; 95% confidence interval, 1.2-12.0) and PICC (P=0.01; odds ratio, 8.2; 95%
      confidence interval, 1.6-41.7). The incidence of thrombosis was higher in FVCs
      than in UVCs and PICCS, that is, 7.8% (5/64), 1.7% (7/407), and 1.1% (2/185),
      respectively (P<0.01). The number of thrombotic events per 1000 catheter days was
      12.3 in FVCs, 3.2 in UVCs, and 1.5 in PICCs (P<0.05). We concluded that
      thrombosis occurs more frequently in FVCs than in other CVCs.

PMID- 29016414
TI  - Prenatal Diagnosis of a Melanotic Neuroectodermal Tumor of Infancy (MNTI): A Case
      Report With a Favorable Outcome After Chemotherapy Failure and Incomplete
      Resection.
AB  - We present the case of a woman referred to our department at 34 weeks of
      pregnancy with a fetal ultrasonographic scan showing a mass that had developed
      within the right maxilla with invasion of the orbit. A retrospective examination
      showed that this tumor had been present since the 12th week of pregnancy. At 39+4
      weeks of gestation, a boy was born. He presented a black firm aspect in the
      maxilla. A computed tomographic scan and magnetic resonance imaging revealed a
      soft tissue swelling over the right maxilla, extending into the orbit but without
      invasion of the globe. Surgical biopsy confirmed a melanotic neuroectodermal
      tumor of infancy. The pathologic examination did not show any neuroblast-like
      component on the hematoxylin eosin saffron staining. Because of the extension and
      the size of the lesion, neoadjuvant chemotherapy was carried out. At day 21, the
      patient received 1 cycle of low-dose cyclophosphamide and vincristine, 2 cycles
      of etoposide and carboplatin, and thereafter 1 cycle of cyclophosphamide,
      adriamycin, and vincristin because the lesion kept growing. After stabilization
      of the size of the tumor, at 4 months, a maxillectomy and partial resection of
      the orbital floor and lateral orbital wall was performed on the patient. As a
      complete resection would have required orbital exenteration, surgery was
      performed deliberately incomplete leaving a macroscopic residue (R2). At 2.5
      years of follow-up, the patient showed complete remission with no lesions evident
      on magnetic resonance imaging.

PMID- 29016415
TI  - Prognostications in Health Care.
AB  - There are health care issues that have been around for decades, which may likely
      continue: rationed health care, rising costs, patient safety, ageing populations,
      and transitional care techniques. Current issues include these, plus their
      evolutionary variations such as new technologies, the changing health care
      landscape, and subsequent emerging ethical issues. Where will it all go? No one
      knows.

PMID- 29016416
TI  - The New Age of Bullying and Violence in Health Care: Part 3: Managing the
      Bullying Boss and Leadership.
AB  - PURPOSE/OBJECTIVES: PRIMARY PRACTICE SETTING(S):: Applicable to all health care
      sections where case management is practiced. FINDINGS/CONCLUSIONS: This article
      is the third of a 4-part series on the topic of bullying in the health care
      workplace. Part 3 addresses the dimensions of the bullying boss and leadership,
      posing major implications for patient safety plus the mental health of staff
      members. The complex constructs and dynamics broached by the bullying boss and
      department leadership are explored. These include the underlying forces at play
      such as power, gender, leadership styles, plus weaves in assessment models.
      Strategic and proactive management of bullying by leadership is vital to
      workforce retention and well-being. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE:
      The increasing incidence and impact of bullying across all sectors have made it a
      major workforce performance management challenge. Health care settings are
      especially tense environments, often making it difficult for individuals to
      distinguish between bullying behavior and high expectations for staff. Bullying
      impacts both direct targets and bystanders who witness the assaultive behaviors,
      with ethical implications as well.Case management is poised to promote a safe
      health care workplace for patients and practitioners alike amid these intricate
      circumstances. Understanding types of bullying bosses and leadership styles is
      integral to a case manager's success in the workplace.

PMID- 29016418
TI  - Improving Posthospital Discharge Telephone Reach Rates Through Prehospital
      Discharge Face-to-Face Meetings.
AB  - PURPOSE OF THE STUDY: The purpose of this study was to determine whether a face
      to-face meeting with patients by a telephonic case manager prehospital discharge
      would result in increased telephone follow-up (TFU) reach rates posthospital
      discharge. PRIMARY PRACTICE SETTING: Acute care adult medicine inpatient units.
      METHODOLOGY AND SAMPLE: A quasiexperimental design was utilized. Two adult
      inpatient medicine units were selected as the intervention and comparison groups.
      The framework of the study is the transitions theory. A convenience sampling
      technique was used, whereby 88 eligible patients on the intervention unit
      received face-to-face meetings prehospital discharge whereas 123 patients on the
      comparison unit received standard care (no face-to-face meetings). Cross
      tabulation and chi-square tests were employed to examine the association of face
      to-face meeting intervention and TFU reach rates. RESULTS: Implementing brief
      (<10 min) face-to-face meetings by a telephonic case manager prehospital
      discharge resulted in a TFU reach rate of 87% on the intervention unit, whereas
      the comparison unit only had a 58% TFU reach rate (p < .001). IMPLICATIONS FOR
      CASE MANAGEMENT PRACTICE: Increasing reach rates by a telephonic case manager
      facilitates communication with more patients posthospital discharge. A brief
      prehospital discharge face-to-face meeting with patients assisted them to
      understand the reasons for a posthospital discharge telephone call, identified
      the best times to call using accurate telephone numbers, and taught patients how
      best to prepare for the call. In addition, by meeting patients face-to-face, the
      telephonic case manager was no longer an unknown person on the telephone asking
      them questions about their medical condition. These factors combined may have
      significantly helped to increase TFU reach rates.

PMID- 29016421
TI  - Know Who Your People Are.

PMID- 29016420
TI  - Prevention Strategies in Post-TBI Depression in Older Adults: A Case Study.
AB  - PURPOSE: The purpose of this study was to describe a theoretically focused
      intervention aimed toward chronic stress and depressive symptom management that
      is coordinated by a case manager and delivered within a home environment by the
      caregiver. PRIMARY PRACTICE SETTING: Home care, community setting. METHODS: A
      case study of an older adult with traumatic brain injury (TBI) secondary to a
      fall who had significant allostatic load at the time of his injury. "Allostatic
      load" is a theoretical construct that suggests the brain is experiencing chronic
      strain on its systems that flexibly respond to stressors. Sustained allostatic
      load can contribute to chronic conditions and poor outcomes. FINDINGS: Through
      actions with the family as caregivers, the case manager was able to coordinate a
      structured home setting and gradual resumption of social activities for this
      older adult. Focus was on establishing structure, meaningful social interactions,
      and positive home experiences that maximized the older adult's interests and
      capacity and mitigated chronic stress. Gradually, the older adult returned to his
      preinjury capacity and lives independently within the family home. IMPLICATIONS
      FOR CASE MANAGEMENT PRACTICE: The case management process has the potential to
      mitigate stressors and improve depression management through family-focused care.
      Although there is limited guidance on prevention of depression, this approach
      resulted in attainment of safe home care, no hospital readmissions, and return to
      previous lifestyle for the older adult. This could be useful in the prevention of
      post-TBI depression.

PMID- 29016422
TI  - Professional Case Managers Modeling the Way: The Case Management Model Act.

PMID- 29016423
TI  - Multistate Licensure Paves the Way for Greater Access to Telephonic Case
      Management.

PMID- 29016424
TI  - Travel and the Professional Case Manager.

PMID- 29016426
TI  - The Epidemiology of Brachial Plexus Birth Palsy in the United States: Declining
      Incidence and Evolving Risk Factors.
AB  - BACKGROUND: The epidemiology of brachial plexus birth palsy (BPBP) in the United
      States may be changing over time due to population-level changes in obstetric
      care. METHODS: The Kids' Inpatient Database from 1997 to 2012 was analyzed.
      Annual estimates of BPBP incidence and disease determinant distribution were
      calculated for the general population and the study population with BPBP. Long
      term trends were analyzed. A multivariate logistic regression model was used to
      quantify the risk associated with each determinant. RESULTS: The database yielded
      a combined total of 5,564,628 sample births extrapolated to 23,385,597 population
      births. The population incidence of BPBP dropped 47.1% over the 16-year study
      period, from 1.7 to 0.9 cases per 1000 live births (P<0.001). Female, black, and
      Hispanic subgroups had moderately increased risks of BPBP. Among children with
      BPBP, 55.0% had no identifiable risk factor. Shoulder dystocia was the strongest
      risk factor for BPBP in the regression model [odds ratio (OR), 113.2; P<0.001],
      although the risk of sustaining a BPBP in the setting of shoulder dystocia
      decreased from 10.7% in 1997 to 8.3% in 2012 (P=0.006). Birth hypoxia was
      independently associated with BPBP (OR, 3.1; P<0.001). Cesarean delivery (OR,
      0.16; P<0.001) and multiple gestation birth (OR, 0.45; P<0.001) were associated
      with lower incidence of BPBP. Notably, the rate of cesarean delivery increased by
      62.8% during the study period, from 20.9% in 1997 to 34.0% in 2012 (P<0.001).
      CONCLUSIONS: Over a 16-year period, the incidence of BPBP fell dramatically,
      paralleled by a significant increase in the rate of cesarean delivery. Systemic
      changes in obstetric practice may have contributed to these trends. As more than
      half of BPBP cases have no identifiable risk factor, prospective investigation of
      established risk factors and characterization of new disease determinants are
      needed to more reliably identify infants at greatest risk. Racial and geographic
      inequalities in disease burden should be investigated to identify interventional
      targets. LEVEL OF EVIDENCE: Level III-case series.

PMID- 29016425
TI  - Diagnostic value of 99mTc-ubiquicidin scintigraphy in differentiation between
      osteomyelitis and bone tumors.
AB  - AIM: The differentiation of osteomyelitis from bone tumors is of great importance
      in clinical decision-making; however, the features of both osteomyelitis and bone
      tumors are noncontributory. Tc-ubiquicidin scintigraphy is a new promising method
      with the ability to specifically localize the infection site by bacterial cell
      membrane binding. This study aimed to evaluate the ability of this radiopeptide
      for the differentiation of these two entities. PATIENTS AND METHODS: Thirty
      consecutive patients (mean age=20.9 years) suspected of having either
      osteomyelitis or bone tumor were included in this prospective study. A Tc-UBI
      scan was performed in both dynamic and static phases and the images were assessed
      qualitatively and semiquantitatively. The final diagnosis was established for 29
      patients on the basis of surgical findings and microbiological and pathology
      assessments as well as any other clinical, laboratory, or imaging findings during
      patient follow-up. RESULTS: The final diagnosis was infectious and noninfectious
      processes in 19 and 10 patients, respectively. Visual assessment could not
      distinguish between osteomyelitis and bone tumors. However, the time-activity
      pattern of the images proved to be promising. The sensitivity, specificity,
      negative and positive predictive value, and accuracy of the time-activity curve
      for osteomyelitis were 73.6 (54-93), 100, 66.6 (43-91), 100, and 82%,
      respectively. The mean+/-SD tumor/nontumor (T/NT) ratios for 30 min images were
      2.22+/-0.45 and 2.02+/-0.51 for infectious and noninfectious processes,
      respectively (P=0.29). Using a cutoff value of 0.97 for the T/NT ratio, the
      sensitivity and specificity were calculated to be 78.9 and 50%, respectively.
      CONCLUSION: Although Tc-UBI scintigraphy in the dynamic imaging format was very
      useful with high accuracy in differentiating between infectious and tumoral
      lesions, it was not useful to distinguish these two entities on the basis of
      visual assessment or T/NT ratio measurement on static images. The study also
      showed the high accuracy of this noninvasive modality in acute osteomyelitis with
      low diagnostic value in chronic infectious processes.

PMID- 29016427
TI  - Comparison of Intended Lengthening of Magnetically Controlled Growing Rods:
      Ultrasound Versus X-Ray.
AB  - BACKGROUND: In the treatment of early onset scoliosis (EOS), there has been a
      trend to use magnetically controlled growing rods (MCGR) in order to reduce the
      number of surgeries. To confirm the amount of lengthening, spine radiographs were
      required. Recently, ultrasound (US) has been added to monitor lengthening of MCGR
      to avoid radiation exposure. Our aim was to determine whether US is as accurate
      as plain radiography (x-ray) in determining the amount of length achieved at
      individual MCGR lengthening episodes. METHODS: Retrospective study; inclusion
      criteria: EOS cases with dual MCGR with minimum 12 months follow-up. Intended
      lengthening IL (mm), lengthening on US (mm) and x-ray (mm) were documented from
      medical records for both right and left rods. Primary (no surgery before MCGR)
      and conversion (other types of instrumentation were replaced with MCGR) cases
      were reviewed separately. P-values determined with analysis of variance. RESULTS:
      Sixteen cases with 100 lengthening episodes met the inclusion criteria. Eleven
      were primary MCGR cases with 67 episodes. Mean follow-up was 19+/-5 months.
      Significant differences were found between IL (3.4+/-1 mm), US (2.7+/-1.9 mm),
      and x-ray (4.1+/-2.2 mm) (P<0.001). The difference between IL and x-ray was
      minimal, but statistically significant (P=0.046). US showed statistically lower
      values than both IL (P=0.001) and x-ray (P<0.001). The mean ratio of x-ray/IL,
      US/IL, and US/x-ray were 1.1, 0.75, and 0.84, respectively. Five conversion cases
      had 33 episodes. Mean follow-up was 21+/-2 months. Significant differences were
      found between IL (3.4+/-0.8 mm), US (1.3+/-0.8 mm), and x-ray (1.7+/-0.9 mm)
      (P<0.001) but there was no significant difference between US and x-ray (P=0.283).
      IL was significantly higher than both US (P< 0.001) and x-ray (P<0.001). The mean
      ratio of x-ray/IL, US/IL, and US/x-ray were 0.64, 0.41, and 1.1, respectively.
      CONCLUSIONS: US can provide confirmatory information of noninvasive lengthening
      of MCGR. However, US tended to underestimate the achieved length as measured by x
      ray in primary cases. Conversion cases demonstrate better concordance between US
      and x-ray but in these cases less overall length was achieved at each lengthening
      episode. LEVEL OF EVIDENCE: Level III.

PMID- 29016428
TI  - Functional Outcomes Following Operative Treatment of Tibial Tubercle Fractures.
AB  - BACKGROUND: Quantitative evaluation of the functional results of surgically
      managed tibial tubercle fractures in adolescents is unreported in the orthopaedic
      literature. METHODS: All patients treated surgically for unilateral tibial
      tubercle fractures at a single institution from 2007 to 2011 were invited to
      return for functional evaluation. Fractures were classified using the Ogden
      classification system. Clinical examination at follow-up included passive knee
      range of motion and thigh circumference. Side-to-side knee extension strength
      deficits were evaluated using a Biodex dynamometer. Patient-reported outcomes
      were assessed using the Pediatric-International Knee Documentation Committee
      Subjective Knee Form (Pedi-IKDC), Tegner-Lysholm Knee Scoring Scale, and Visual
      Analog Pain Scale. Chart review was performed to determine postoperative
      protocols including the use of physical therapy and protected weight bearing.
      Functional parameters were compared between the involved and uninvolved
      extremities using the Wilcoxon Signed Ranks Test and the Spearman correlations
      were performed to identify any relationships between perioperative factors,
      functional parameters, and subjective outcomes. RESULTS: In total, 19 of 42
      patients completed clinical and functional testing and 18 of 19 completed all
      outcome surveys. Average age at injury was 13.9 years and average follow-up was
      3.0 years. There was no statistical difference in knee range of motion between
      sides, however, thigh circumference was slightly smaller in the injured extremity
      (median difference, 1.7 cm at 15 cm above the patella and 4.0 cm at 50% of the
      length of the thigh). In total 5/19 subjects (26%) had a significant quadriceps
      extension strength deficit on the involved leg compared with the contralateral
      side. The median Visual Analog Pain Scale for affected limbs was 8/100 and for
      unaffected limbs was 6/100 (P=0.017). The Tegner-Lysholm Scale revealed 9
      excellent results, 5 good, 4 fair, and 1 poor (median, 90/100). Results of the
      Pedi-IKDC were 11 excellent, 3 good, 2 fair, and 3 poor results (median, 91/100).
      Outcome scores did not correlate to diminished strength or thigh circumference.
      No difference in outcome based upon body mass index, postoperative weight-bearing
      status, Ogden classification, or postoperative physical therapy was noted using
      regression analysis. CONCLUSIONS: Despite promising objective results, clinical
      outcomes measured by subjective validated surveys are not all excellent. LEVEL OF
      EVIDENCE: Level III.

PMID- 29016429
TI  - Is Routine Spine MRI Necessary in Skeletally Immature Patients With MHE?
      Identifying Patients at Risk for Spinal Osteochondromas.
AB  - BACKGROUND: Multiple hereditary exostoses (MHE) is an autosomal dominant
      condition leading to development of osteochondromas throughout the body. Although
      long bones are most often affected, spine involvement may occur and usually
      requires advanced imaging for diagnosis. However, the high cost of detection,
      infrequent occurrence, and very low likelihood of spinal cord compression and
      neurological injury, create a management conundrum. The purpose of our
      investigation is to identify patients at greatest risk for spinal lesions and
      refine indications for advanced imaging. METHODS: All MHE patients in a 24-year
      period were retrospectively reviewed. Skeletally immature patients with advanced
      imaging of the spine were further evaluated. The demographic characteristics,
      family history, clinical presentation, past surgical history, tumor burden, and
      distribution of patients with spinal lesions were compared with those without.
      RESULTS: In total, 227 MHE patients were identified and 21 underwent advanced
      spinal imaging. Spinal lesions were found in 8 of the 21 screened patients
      (38.1%, 3.5% overall), of which 4 were intracanal and 1 was symptomatic (4.8%,
      0.4% overall). Only the symptomatic patient underwent excision of the spinal
      lesion. Patients with spinal lesions had higher tumor burden than those without
      (median, 28.5 vs. 19 locations; P=0.010). There was a significant association
      with rib (P=0.018) and pelvic (P=0.007) lesions, which may serve as "harbinger"
      lesions. The presence of both a rib and a pelvic lesion used as a screening tool
      for spinal lesions produces a sensitivity of 100% and specificity of 69%.
      CONCLUSIONS: Symptomatic spinal involvement in children with MHE is rare and
      tends to occur in patients with higher tumor burden. We recommend limiting
      advanced spine imaging to children with neurological symptoms or with rib and
      pelvic "harbinger" lesions. Patients without these findings are unlikely to have
      spine involvement needing intervention. This approach offers an opportunity to
      avoid unnecessary testing and substantially reduce costs of diagnostic imaging.
      LEVEL OF EVIDENCE: Level III.

PMID- 29016430
TI  - An Anatomic and Radiographic Study of the Distal Tibial Epiphysis.
AB  - BACKGROUND: Although the undulating shape of the distal tibial epiphysis is well
      recognized, its anatomic features have not been well quantified in the
      literature. To guide the placement of surgical implants about the distal tibial
      physis, we investigated the topographical anatomy of the distal tibial epiphysis
      and explored the ability of standard radiographs to visualize the physis.
      METHODS: We studied 30 cadaveric distal tibial epiphyses in specimens 3 to 14
      years of age. Anteroposterior (AP) and lateral radiographs were obtained of each
      specimen and then repeated after flexible radiopaque markers were placed on the
      major undulations. All radiographs were analyzed to determine the height or depth
      of each landmark, and measurements with and without markers for each landmark
      were compared using intraclass correlation coefficients (ICC). In 9 specimens,
      similar measurements were obtained on high-resolution 3-dimensional (3D) surface
      scans. RESULTS: There were 4 distinct physeal undulations usually present: an
      anteromedial peak (Kump's bump), a posterolateral peak, an anterior central
      valley, and a posterior central valley. On the 3D scans, Kump's bump averaged 5.0
      mm (range, 3.0 to 6.4 mm), the posterolateral peak 2.4 mm (range, 1.2 to 5.0 mm),
      the anterior valley 1.3 mm (range, 0 to 3.6 mm), and the posterior valley 0.77 mm
      (range, 0 to 2.7 mm). Lateral radiographs with markers correlated with
      measurements from 3D scans better than those without markers (ICC=0.61 vs. 0.24).
      For AP radiographs, correlation was good to excellent regardless of marker use
      (ICC=0.76 vs. 0.66). CONCLUSIONS: There are 4 major undulations of the distal
      tibial physis. Kump's bump is the largest. A centrally placed epiphyseal screw in
      the medial/lateral direction or screws from anterolateral to posteromedial and
      anteromedial to posterolateral would tend to avoid both valleys. Particular
      caution should be taken when placing metaphyseal screws in the anteromedial or
      posterolateral distal tibia. Physeal undulations were more difficult to visualize
      on the lateral view. CLINICAL RELEVANCE: This study provides quantitative data on
      the topography of the distal tibial physis to aid hardware placement. Lateral
      views should be interpreted with caution, as the physeal undulations are not as
      visible, whereas AP views can be interpreted with more confidence.

PMID- 29016431
TI  - Incidence of Congenital Spinal Abnormalities Among Pediatric Patients and Their
      Association With Scoliosis and Systemic Anomalies.
AB  - BACKGROUND: Congenital abnormalities when present, according to VACTERL theory,
      occur nonrandomly with other congenital anomalies. This study estimates the
      prevalence of congenital spinal anomalies, and their concurrence with other
      systemic anomalies. METHODS: A retrospective cohort analysis on Health care Cost
      and Utilization Project's Kids Inpatient Database (KID), years 2000, 2003, 2006,
      2009 was performed. ICD-9 coding identified congenital anomalies of the spine and
      other body systems. OUTCOME MEASURES: Overall incidence of congenital spinal
      abnormalities in pediatric patients, and the concurrence of spinal anomaly
      diagnoses with other organ system anomalies. Frequencies of congenital spine
      anomalies were estimated using KID hospital-and-year-adjusted weights. Poisson
      distribution in contingency tables tabulated concurrence of other congenital
      anomalies, grouped by body system. RESULTS: Of 12,039,432 patients, rates per
      100,000 cases were: 9.1 hemivertebra, 4.3 Klippel-Fiel, 56.3 Chiari malformation,
      52.6 tethered cord, 83.4 spina bifida, 1.2 absence of vertebra, and 6.2
      diastematomyelia. Diastematomyelia had the highest concurrence of other
      anomalies: 70.1% of diastematomyelia patients had at least one other congenital
      anomaly. Next, 63.2% of hemivertebra, and 35.2% of Klippel-Fiel patients had
      concurrent anomalies. Of the other systems deformities cooccuring, cardiac system
      had the highest concurrent incidence (6.5% overall). In light of VACTERL's
      definition of a patient being diagnosed with at least 3 VACTERL anomalies,
      hemivertebra patients had the highest cooccurrence of >=3 anomalies (31.3%). With
      detailed analysis of hemivertebra patients, secundum ASD (14.49%), atresia of
      large intestine (10.2%), renal agenesis (7.43%) frequently cooccured.
      CONCLUSIONS: Congenital abnormalities of the spine are associated with serious
      systemic anomalies that may have delayed presentations. These patients continue
      to be at a very high, and maybe higher than previously thought, risk for
      comorbidities that can cause devastating perioperative complications if not
      detected preoperatively, and full MRI workups should be considered in all
      patients with spinal abnormalities. LEVEL OF EVIDENCE: Level III.

PMID- 29016432
TI  - Is Systemic Inflammatory Response Syndrome Relevant to Pulmonary Complications
      and Mortality in Multiply Injured Children?
AB  - BACKGROUND: Systemic inflammatory response syndrome (SIRS) is a well-recognized
      phenomenon in adult trauma populations. The "initial hit" of the traumatic event
      is often coupled with a systemic immune response characterized by changes in
      vital signs and laboratory indicators. A "second hit" from surgery during this
      time frame often results in acute lung injury, along with deterioration of the
      patient's clinical condition. We hypothesized that children and adolescents would
      experience SIRS physiology, but would not experience adult respiratory distress
      syndrome (ARDS) or "second hit" related death to the extent seen in the adult
      populations. METHODS: We queried the trauma database of our level 1 pediatric
      trauma center from January 2005 to December 2015 for patients with injury
      severity scores of >16. We used the electronic medical record to track SIRS
      criteria in patients days 1 to 4 posttrauma. Trends were examined in patients
      with an orthopaedic injury (OI) and with no orthopaedic injury. Patients were
      further subcategorized and analyzed by age group based on the convention for
      definition of pediatric SIRS. Patients in the orthopaedic cohort were further
      examined for pulmonary complications and death. Logistic regression was used to
      identify risk factors for SIRS physiology in the first 4 days of hospitalization.
      RESULTS: 81.4% (OI) and 69.1% no orthopaedic injury reached the threshold for
      SIRS within their first 4 days of hospitalization. Nine patients died in the
      hospital. Only 3 OI patients developed the criteria for ARDS, and only 3 patients
      with orthopaedic injuries died, 2 died within 24 hours of presentation and 1
      within 48 hours, all had severe brain trauma. Increasing age groups showed
      increasing proportion of patients with SIRS. Increasing injury severity score and
      increasing age were independent predictors of SIRS during days 1 to 4.
      DISCUSSION: SIRS seems to be as common in children as the reported rates for
      adults, and the proportion of SIRS in children increases with increasing age and
      injury severity. The high mortality rate and rate of ARDS observed in adults was
      not observed in our cohort. The presence or absence of major orthopaedic injuries
      was not a significant predictor. The SIRS response in polytraumatized children is
      poorly understood. The clinical phenomenon of acute lung injury/ARDS is observed
      less often in children, but the exact mechanism by which this occurs is unknown.
      LEVEL OF EVIDENCE: Level III-case control.

PMID- 29016433
TI  - Under Correction of Sagittal Deformities Based on Age-adjusted Alignment
      Thresholds Leads to Worse Health-related Quality of Life Whereas Over Correction
      Provides No Additional Benefit.
AB  - STUDY DESIGN: Retrospective review of prospectively-collected database.
      OBJECTIVE: This study aims to compare 2-year clinical outcomes of patients who
      underwent surgical reconstructions based on their achievement to age-adjusted
      alignment ideals. SUMMARY OF BACKGROUND DATA: Recent research in sagittal plane
      has proposed age-adjusted alignment thresholds. However, the impact of these
      thresholds on postoperative health-related quality of life (HRQOL) is yet to be
      investigated. METHODS: Patients were included if they were more than 18-years old
      and underwent surgical correction of adult spinal deformity with a complete 2
      year follow-up. Patients were stratified into three groups based on achievement
      of age-adjusted thresholds in pelvic tilt (PT), pelvic incidence minus lumbar
      lordosis (PI-LL), and sagittal vertical axis (SVA). First group included patients
      who reached the exact age-adjusted threshold +/- 10 years (MATCHED), other two
      groups included patients who were over corrected (OVER), and under corrected
      (UNDER). Clinical outcomes including actual value and offset from age-adjusted
      Oswestry Disability Index, Short-Form-36 (SF-36) -physical component summary, and
      Scoliosis Research Society-22r (SRS-22r) were compared between groups at 2 years
      follow-up. RESULTS: A total of 343 patients (mean, 57 yrs and 83% females) were
      included. Sagittal profile of the population was: PT = 23.6 degrees , SVA = 65.8
      mm, and PI-LL = 15.6 degrees . At 2-year follow-up, there was significant
      improvement in all sagittal modifiers with 25.7%, 24.3%, and 33.1% of the
      patients matching their age alignment targets in terms of PT, PI-LL, and SVA,
      respectively. For PT and PI-LL, the three groups (MATCHED, OVER, and UNDER) had
      comparable values and offsets from age-adjusted patient reported outcome.
      However, for SVA groups, patients in UNDER had significantly worse HRQOL than the
      two other groups. Patients in PT, PI-LL, and SVA UNDER groups were significantly
      younger than the other groups, P < 0.05. CONCLUSION: At 2 years after adult
      spinal deformity surgical treatment, only 24.3% to 33.1% of the patients reached
      age-adjusted alignment thresholds. Those under corrected in SVA demonstrated
      worse clinical outcomes. No significant improvements were found between matched
      and overcorrected patients, with overcorrection being an established risk for
      proximal junctional kyphosis. These results further emphasize the need for
      patient specific operative planning. LEVEL OF EVIDENCE: 3.

PMID- 29016434
TI  - Hypoalbuminemia Is Associated With Septic Revisions After Primary Surgery and
      Postoperative Infection After Revision Surgery.
AB  - STUDY DESIGN: Retrospective database review. OBJECTIVE: To determine (1) the
      relationship between hypoalbuminemia and body mass index (BMI); (2) the
      association between malnutrition and revision spine surgery for septic reasons;
      and (3) the association between malnutrition and infection after aseptic revision
      spine surgery. SUMMARY OF BACKGROUND DATA: Although malnutrition has been
      suggested to increase the risk of infection after spine surgery, evidence
      supporting this hypothesis is conflicting. METHODS: Patients undergoing revision
      spine surgery were identified in the American College of Surgeons National
      Surgical Quality Improvement Program (ACS-NSQIP) from 2006 to 2014.
      Hypoalbuminemia (albumin < 3.5 g/dL) was used as a surrogate marker of
      malnutrition. Multivariate analysis was used to assess the association of
      hypoalbuminemia with septic versus aseptic revision spine surgery. The
      association between hypoalbuminemia and deep infection postoperatively within 30
      days of aseptic revision surgeries was also assessed. RESULTS: A total of 3136
      patients who underwent revision spine surgery were identified; 2922 (93.2%)
      underwent surgery for aseptic reasons, and 214 (6.8%) for septic reasons.
      Hypoalbuminemia was present in all BMI groups including obese patients, though it
      was highest in underweight patients (22.4%). Patients who underwent surgery for
      septic reasons had a higher rate of hypoalbuminemia than those undergoing surgery
      for aseptic reasons (49.1% vs. 8.5%, P < 0.001) with nine times the odds of
      having hypoalbuminemia (adjusted odds ratio, OR = 9.17, P < 0.001). Of the 2922
      patients undergoing revision spine surgery for aseptic reasons, hypoalbuminemia
      was independently associated with acute deep infection within 30 days of surgery
      (adjusted OR = 2.85, P = 0.019). CONCLUSION: Malnutrition is more common in
      revision spine surgery for septic reasons when compared with aseptic revision
      surgery. Acute postoperative infection following aseptic revision surgery is also
      more common in patients with malnutrition. Further study, in the form of
      prospective trials, will help to increase our understanding of the effects of
      malnutrition in spine surgery. LEVEL OF EVIDENCE: 3.

PMID- 29016435
TI  - Comparison of Outcomes for Anterior Cervical Discectomy and Fusion With and
      Without Anterior Plate Fixation: A Systematic Review and Meta-Analysis.
AB  - STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To compare
      postoperative surgical, radiographic, and patient-reported outcomes following
      anterior cervical discectomy and fusion (ACDF) with and without plate fixation.
      SUMMARY OF BACKGROUND DATA: ACDF has evolved significantly over the years,
      including the placement of an anterior plate construct. Although promoting bony
      osseo-integration at the fusion site, there are a number of plate-related
      complications that can arise. The non-plating approach is less invasive, however,
      greater rates of cage subsidence have been associated with this model. METHODS:
      We performed an electronic literature search for human studies that directly
      compared ACDF with and without anterior plate fixation. Outcomes of interest
      comprised of postoperative dysphagia, fusion success, and cage subsidence as well
      as patient reported outcomes, including the Neck Disability Index (NDI) scores
      and Visual Analog Scale (VAS) for both neck and arm pain. RESULTS: A total of 15
      studies (12 observational and 3 randomized controlled trials) and 893 patients
      (57% males) were included. Overall, ACDF with plate fixation was associated with
      significantly higher vertebral fusion rates (odds ratio [OR] 1.98; 95% confidence
      interval [CI] 1.16-3.37), lower subsidence rates (odds ratio [OR] 0.31, 95% CI
      0.18-0.52), and more favorable VAS-neck pain scores at last follow-up (mean
      difference [MD] 0.59, 95% CI -0.78 to -0.41). Conversely, ACDF procedures without
      plate fixation had marginally better long-term VAS-arm pain scores (mean
      difference [MD] 0.2, 95% CI 0.04-0.36). No difference was found with regards to
      dysphagia (OR 1.21, 95% CI, 0.57-2.56) and NDI (MD 0.06, 95% C.I -0.54 to 0.42).
      CONCLUSION: Available evidence, although limited, suggests superior surgical
      outcomes in ACDF procedures with anterior plate fixation (increased fusion,
      decreased subsidence) and slightly better VAS-neck pain scores at last follow-up.
      Future longitudinal, multicenter randomized controlled trials should be completed
      to validate any associations found in this study. LEVEL OF EVIDENCE: 3.

PMID- 29016436
TI  - Trends and Disparities in Cervical Spine Fusion Procedures Utilization in the New
      York State.
AB  - STUDY DESIGN: A retrospective review of the Statewide Planning and Research
      Cooperative System database of the New York State. OBJECTIVE: This study examined
      the rate of increase of cervical spine fusion procedures at low-, medium-, and
      high-volume hospitals, and analyzed racial and socioeconomic characteristics of
      the patient population treated at these three volume categories. SUMMARY OF
      BACKGROUND DATA: There has been a steady increase in spinal fusion procedures
      performed each year in the United States, especially cervical and lumbar fusion.
      Our study aims to analyze the rate of increase at low-, medium-, and high-volume
      hospitals, and socioeconomic characteristics of the patient populations at these
      three volume categories. METHODS: The New York State, Statewide Planning and
      Research Cooperative System (SPARCS) database was searched from 2005 to 2014 for
      the International Classification of Diseases, Ninth Revision, Clinical
      Modification (ICD-9-CM) Procedure Codes 81.01 (Fusion, atlas-axis), 81.02
      (Fusion, anterior column, other cervical, anterior technique), and 81.03 (Fusion,
      posterior column, other cervical, posterior technique). Patients' primary
      diagnosis (ICD-9-CM), age, race/ethnicity, primary payment method, severity of
      illness, length of stay, hospital of operation were included. All 122 hospitals
      were categorized into high-, medium-, and low-volume. Trends in annual number of
      cervical spine fusion surgeries in each of the three hospital volume groups were
      reported using descriptive statistics. RESULTS: Low-volumes centers were more
      likely to be rural and non-teaching hospitals. African American patients
      comprised a greater portion of patients at low-volume hospitals, 15.1% versus
      11.6% compared with high-volume hospitals. Medicaid and self-pay patients were
      also overrepresented at low-volume centers, 6.7% and 3.9% versus 2.6% and 1.7%,
      respectively. Compared with Caucasian patients, African American patients had
      higher rates of postoperative infection (P = 0.0020) and postoperative bleeding
      (P = 0.0044). Compared with privately insured patients, Medicaid patients had a
      higher rate of postoperative bleeding (P = 0.0266) and in-hospital mortality (P =
      0.0031). CONCLUSION: Our results showed significant differences in hospital
      characteristics, racial distribution, and primary payments methods between the
      low- and high-volume categories. African American and Medicaid patients had
      higher rates of postoperative bleeding, despite similar rates between the three
      volume categories. This suggests racial and socioeconomic disparities remains
      problematic for disadvantaged populations, some of which may be attributed to
      accessibility to care at high-volume centers. LEVEL OF EVIDENCE: 3.

PMID- 29016437
TI  - A Mouse Intervertebral Disc Degeneration Model by Surgically Induced Instability.
AB  - STUDY DESIGN: An experimental study to develop a mouse model of lumbar
      intervertebral disc degeneration (IDD). OBJECTIVE: The aim of this study was to
      develop a mouse lumbar IDD model using surgically induced instability and to
      compare the findings of this model to those in human IDD. SUMMARY OF BACKGROUND
      DATA: Previously, various kinds of inducers have been used to reproduce IDD in
      experimental animals; however, there is yet no standard mouse lumbar IDD model
      without direct injury to intervertebral disc. METHODS: A total number of 59
      C57BL/6J male mice at 8 weeks old were used. Instability of lumbar spine was
      induced by surgical resection of posterior elements, including facet joints,
      supra- and interspinous ligaments. We then analyzed time course changes in
      radiographical (n = 17) and histological analyses (n = 42), and compared these
      findings with those in human IDD. RESULTS: Radiographical analyses showed that
      the disc height began to decrease in the first 2 weeks after the surgery, and the
      decrease continued throughout 12 weeks. Bone spurs at the vertebral rims were
      observed in the late stage of 8 and 12 weeks after the surgery. Histological
      analyses showed that the disorder of the anterior anulus fibrosus (AF) was
      initially obvious, followed by posterior shift and degeneration of the nucleus
      pulposus (NP). Proteoglycan detected in inner layer of AF and periphery of NP was
      decreased after 8 weeks. Immunohistochemistry displayed the increase of type I
      and X collagen, and matrix metalloproteinase 13 in the anterior AF. CONCLUSION:
      Surgical resection of posterior elements of mouse lumbar spine resulted in
      reproducible IDD. Because the present procedure does not employ direct injury to
      intervertebral disc and the radiological and histological findings are compatible
      with those in human IDD, it may contribute to further understanding of the native
      pathophysiology of IDD in future. LEVEL OF EVIDENCE: N/A.

PMID- 29016438
TI  - ONO-1301 Enhances in vitro Osteoblast Differentiation and in vivo Bone Formation
      Induced by Bone Morphogenetic Protein.
AB  - STUDY DESIGN: In vitro and in vivo assessment of osteogenic effect by
      prostacyclin agonist (ONO-1301). OBJECTIVE: The aim of this study was to
      investigate the effects of ONO-1301 on in vitro osteoblastic differentiation and
      in vivo bone formation induced by bone morphogenetic protein (BMP). SUMMARY OF
      BACKGROUND DATA: Among prostaglandins (PGs), PGE2 is the most abundant in bone
      tissue and its effects on bone formation have been well studied. PGI2
      (prostacyclin) is the second most abundant PG in bone tissue and plays important
      roles in hemodynamics. However, the effects of PGI2 on osteoblast differentiation
      and bone regeneration have not been elucidated. METHODS: The effects of PGI2
      agonist (ONO-1301), with and without recombinant human (rh) BMP-2, on
      osteoblastic differentiation and cell proliferation were investigated in vitro
      using alkaline phosphatase (ALP) and WST-1 assays. Murine primary osteoblasts and
      cell lines (ST2, MC3T3-E1, C2C12, and CH310T1/2) were used for the study. The
      effects of ONO-1301 on rhBMP-2 induced bone formation were investigated in a
      mouse model of muscle pouch transplantation (ectopic model) and in a rat model of
      spinal fusion (orthotopic model). RESULTS: ONO-1301 significantly increased ALP
      activity in the primary osteoblasts and ST2 cells. In addition, cotreatment with
      ONO-1301 and rhBMP-2 significantly increased ALP activity in the primary
      osteoblasts, as well as in ST2 and MC3T3-E1 cells. Cell proliferation was not
      affected by both ONO-1301 and ONO-1301 as well as rhBMP-2. In the ectopic model,
      ONO-1301 significantly increased the volume of ectopic bone whose formation was
      induced by BMP. In addition, in the orthotopic model, ONO-1301 significantly
      increased bone volume and fusion rate. CONCLUSION: This study has demonstrated
      that the PG IP agonist ONO-1301 improves in vitro BMP-2 induced osteoblast
      differentiation and in vivo ectopic and orthotopic bone formation. The results
      suggest that ONO-1301 has a potential clinical application as an enhancer of BMP
      induced bone formation. LEVEL OF EVIDENCE: N/A.

PMID- 29016439
TI  - Examining the Ability of Artificial Neural Networks Machine Learning Models to
      Accurately Predict Complications Following Posterior Lumbar Spine Fusion.
AB  - STUDY DESIGN: A cross-sectional database study. OBJECTIVE: The aim of this study
      was to train and validate machine learning models to identify risk factors for
      complications following posterior lumbar spine fusion. SUMMARY OF BACKGROUND
      DATA: Machine learning models such as artificial neural networks (ANNs) are
      valuable tools for analyzing and interpreting large and complex datasets. ANNs
      have yet to be used for risk factor analysis in orthopedic surgery. METHODS: The
      American College of Surgeons National Surgical Quality Improvement Program (ACS
      NSQIP) database was queried for patients who underwent posterior lumbar spine
      fusion. This query returned 22,629 patients, 70% of whom were used to train our
      models, and 30% were used to evaluate the models. The predictive variables used
      included sex, age, ethnicity, diabetes, smoking, steroid use, coagulopathy,
      functional status, American Society for Anesthesiology (ASA) class >=3, body mass
      index (BMI), pulmonary comorbidities, and cardiac comorbidities. The models were
      used to predict cardiac complications, wound complications, venous
      thromboembolism (VTE), and mortality. Using ASA class as a benchmark for
      prediction, area under receiver operating curves (AUC) was used to determine the
      accuracy of our machine learning models. RESULTS: On the basis of AUC values, ANN
      and LR both outperformed ASA class for predicting all four types of
      complications. ANN was the most accurate for predicting cardiac complications,
      and LR was most accurate for predicting wound complications, VTE, and mortality,
      though ANN and LR had comparable AUC values for predicting all types of
      complications. ANN had greater sensitivity than LR for detecting wound
      complications and mortality. CONCLUSION: Machine learning in the form of logistic
      regression and ANNs were more accurate than benchmark ASA scores for identifying
      risk factors of developing complications following posterior lumbar spine fusion,
      suggesting they are potentially great tools for risk factor analysis in spine
      surgery. LEVEL OF EVIDENCE: 3.

PMID- 29016440
TI  - The Feature of Clinical and Radiographic Outcomes in Elderly Patients With
      Cervical Spondylotic Myelopathy: A Prospective Cohort Study on 1025 Patients.
AB  - STUDY DESIGN: A prospective cohort study. OBJECTIVE: The purpose of this study
      was to compare the surgical outcomes between nonelderly and elderly patients with
      cervical spondylotic myelopathy (CSM) and to characterize the preoperative
      symptoms and postoperative residual symptoms in elderly patients. SUMMARY OF
      BACKGROUND DATA: Age at the time of surgery influences the surgical outcome.
      However, no report has elucidated residual symptoms after surgery in elderly
      patients with CSM. We designed a large-scale cohort study examining the surgical
      outcomes of CSM in elderly patients from a single surgery. METHODS: A total of
      1025 consecutive patients with CSM (642 men and 383 women; mean age, 64.4 yr;
      range, 23-93 yr) who underwent laminoplasty were included. Patients were divided
      into three groups based on age: nonelderly (<65 yr), young-old (65-74 yr), and
      old-old (>=75 yr), and the number of patients in each group was 488, 329, and
      208, respectively. The pre- and postoperative neurological statuses were
      evaluated using the Japanese Orthopaedic Association (JOA) scoring system for
      cervical myelopathy. The recovery rate (RR) of each function was compared among
      the three groups. Radiographic data including alignment and range of motion were
      also assessed. RESULTS: The mean preoperative JOA scores of motor function of the
      lower extremity in nonelderly, young-old, and old-old groups were 2.8, 2.2, and
      1.6, respectively (P < 0.0001). Elderly patients showed significantly lower JOA
      scores for bladder function than nonelderly patients (2.7, 2.5, and 2.2, P <
      0.0001). Cervical lordosis in the neutral position increased gradually with age.
      Total range of motion decreased with increasing age. After surgery, the mean RRs
      of motor function of the lower extremity were 57.7%, 38.6%, and 24.0%,
      respectively. Gait disturbance significantly increased with age (P < 0.0001).
      CONCLUSION: Postoperative gait disturbance persisted more than other symptoms in
      elderly patients than in nonelderly patients. LEVEL OF EVIDENCE: 2.

PMID- 29016441
TI  - Epidemiology and Outcomes of Infectious Spondylodiscitis in Hemodialysis
      Patients.
AB  - STUDY DESIGN: A retrospective study of patients who were hospitalized for
      infectious spondylodiscitis over a 13-year period. OBJECTIVE: To elucidate the
      epidemiology and prognostic factors of infectious spondylodiscitis in
      hemodialysis (HD) patients and to identify the impact of HD on infectious
      spondylodiscitis. SUMMARY OF BACKGROUND DATA: Only a few case studies of
      infectious spondylodiscitis in HD patients can be found in the literature.
      Reports of prognostic factors are limited and patients' outcomes have not been
      well described. METHODS: The cases of 1402 patients who were hospitalized for
      infectious spondylodiscitis over a 13-year period were retrospectively reviewed.
      Of these, 102 patients on maintenance HD were enrolled in this study. Cox
      proportional hazard model was used to evaluate the risk factors of mortality and
      recurrence. RESULTS: The 102 enrolled patients had an average age 63.3 +/- 11.2
      years old and male-to-female ratio of 1:1.04. Back pain was present in 75.5% of
      patients and the most commonly infected site was the lumbosacral spine. Infection
      associated with vascular access was identified in 31.4% of patients. The
      prevalence of dialysis via central venous catheters was higher than prevalent HD
      patients. Methicillin-resistant Staphylococcus aureus was the most common
      pathogen, followed coagulase-negative staphylococci. The patients' in-hospital
      survival rate was 82.4%; their vascular access survival rate was 75.5%; their 1
      year survival rate was 78.4%, and their 1-year recurrence rate was 20.2%.
      Congestive heart failure was associated with an increased 1-year mortality. Other
      variables exhibited no significant relationship with patients' in-hospital
      mortality, 1-year mortality or recurrence. CONCLUSION: The characteristics and
      outcomes of infectious spondylodiscitis in HD patients were elucidated. Most of
      the demographic and clinical variables, evaluated upon admission, did not predict
      mortality or recurrence. LEVEL OF EVIDENCE: 3.

PMID- 29016442
TI  - Recommencement of Denosumab for Unresectable Giant Cell Tumor of the Cervical
      Spine: A Case Report.
AB  - STUDY DESIGN: A case report. OBJECTIVE: The aim of this study was to highlight
      that rapid progression or recurrence of giant cell tumor of the bone (GCTB) can
      still occur with cessation of Denosumab in the management of unresectable GCTB
      even in cases with prior demonstration of excellent response to treatment and
      stable disease over a protracted length of surveillance despite dose reduction.
      The close proximity of unresectable GCTB to vital structures makes it prudent
      that we monitor these patients closely given its locally aggressive nature.
      SUMMARY OF BACKGROUND DATA: Cervical spine GCTB is extremely rare. Unresectable
      GCTB has historically been a challenge to treat due to the lack of prospective,
      randomized clinical trials to guide treatment. Radiotherapy has fallen out of
      favor due to the risk of malignant transformation, especially as most GCTB
      patients are young.In recent years, improved understanding of the receptor
      activator of nuclear factor-kappaB ligand (RANKL) in the pathophysiology of GCTB
      has led to the use of Denosumab in patients with
      recurrent/unresectable/metastatic GCTB and in patients whom surgical resection
      carries a high morbidity. To date, the optimal dosage and duration of therapy in
      the treatment of GCTB is unknown. METHODS: We report a case of cervical spine
      GCTB in a 53-year-old male with positive surgical margins managed with Denosumab.
      RESULTS: This is the first reported case of a cervical spine GCTB managed with
      Denosumab showing excellent response to treatment, recurrence of disease post
      cessation of Denosumab despite earlier satisfactory disease control and
      stabilization achieved even with dose reduction, and again an excellent response
      with recommencement of the drug. CONCLUSION: Denosumab is an excellent option in
      patients with unresectable GCTB or when surgery will result in excessive
      morbidity. However, further studies are required to determine optimal dosing,
      treatment duration, side effect profile, and whether Denosumab is truly able to
      achieve partial or complete disease remission in the long run. LEVEL OF EVIDENCE:
      4.

PMID- 29016444
TI  - The more lordosis of cage, the better?

PMID- 29016443
TI  - Development and Validation of Taiwanese Version of the Neck Disability Index.
AB  - STUDY DESIGN: Cross-cultural adaptation and cross-sectional psychometric testing
      in a convenience sample of patients with neck pain. OBJECTIVE: To translate and
      cross-culturally adapt the Neck Disability Index (NDI) into a Taiwanese version
      and to assess the psychometric properties. SUMMARY OF BACKGROUND DATA: The
      Taiwanese NDI has not been developed or validated. METHODS: The NDI was first
      translated and culturally adapted to the Taiwanese version. The test-retest
      reliability within 1 week was examined (n = 32). The factor structure was
      assessed by confirmatory factor analysis (n = 137). The construct validity was
      assessed by examining the relationship between the NDI and other well-known
      measures (n = 137). RESULTS: The Taiwanese version was successfully translated
      and cross-culturally adapted. The internal consistency was excellent, with
      Cronbach alpha = 0.89. High test-retest reliability was demonstrated with
      intraclass correlation coefficients of 0.87. The minimal detectable change was
      8.74. The two-factor model (pain and function factors) was better than the one
      factor model, with higher factor loadings and better goodness-of-fit statistics.
      The convergent validity was supported by moderate correlation of the pain factor
      with the Visual Analogue Scale (|rho| = 0.45), and high correlation of the
      function factor with the physical component summary of the Short-From 36 (SF-36)
      (|rho| = 0.60). CONCLUSION: The Taiwanese NDI is a reliable and valid disease
      specific measure for assessment of pain and functional status in patients with
      neck pain. LEVEL OF EVIDENCE: 3.

PMID- 29016445
TI  - Point of View: Avoiding Opioids in Patients With Work-related Lumbar Disc
      Herniation.

PMID- 29016446
TI  - Incidence and Risk Factors of Acute Pancreatitis After Scoliosis Surgery: A
      Prospective Study.
AB  - STUDY DESIGN: A prospective study. OBJECTIVE: To investigate the incidence and
      risk factors of acute pancreatitis after scoliosis surgery. SUMMARY OF BACKGROUND
      DATA: Pancreatitis has been recognized as a possible complication of extra
      abdominal surgeries. However, there were few reports on the incidence and risk
      factors of acute pancreatitis after scoliosis surgery. METHODS: A prospective
      clinical study was performed at our center from September 2014 to October 2015.
      One hundred seventy-six patients undergoing posterior spinal correction surgery
      were enrolled. The diagnosis of acute pancreatitis was based on their clinical
      manifestations combined with laboratory examination. Demographic, intraoperative,
      and radiological parameters were evaluated to identify the risk factors of acute
      pancreatitis after scoliosis surgery. RESULTS: Thirteen patients (7.4%) were
      diagnosed with acute pancreatitis. Compared with patients without pancreatitis,
      pancreatitis patients had lower body mass index (BMI) (15.5 vs. 19.5, P = 0.001),
      larger preoperative Cobb angle of major curve (87.5 degrees  vs. 59.2 degrees , P
      < 0.001), lower correction rate (57.4% vs. 69.0%, P = 0.045), lower
      intraoperative mean arterial pressure (57.9 mmHg vs. 66.1 mmHg, P < 0.001), and
      longer fusion levels (13.3 vs. 10.1, P < 0.001). No significant differences were
      noted with respect to operation time, intraoperative blood loss, or the amount of
      sagittal profile correction. Furthermore, multivariate logistic analysis revealed
      that BMI (odds ratio [OR] = 1.542, P = 0.009), lowest intraoperative mean
      arterial pressure (OR = 1.126, P = 0.039), and segments of fusion (OR = 0.551, P
      = 0.025) were independent risk factors for postoperative acute pancreatitis. All
      cases were treated with bowel rest, intravenous fluids, and fasting and
      completely recovered with 3.3 (2-5) days. CONCLUSION: The incidence of
      postoperative acute pancreatitis after scoliosis surgery was 7.4%. The low BMI,
      lowest intraoperative mean arterial pressure, and long segments of fusion were
      independent risk factors for acute pancreatitis after scoliosis surgery. LEVEL OF
      EVIDENCE: 3.

PMID- 29016447
TI  - Systemic Inflammation in Lewy Body Diseases: A Systematic Review.
AB  - Few studies have investigated the role of inflammation in Lewy body dementia
      (LBD) and variable results have been found. We systematically reviewed the
      literature for evidence of systemic inflammatory changes in dementia with Lewy
      bodies and Parkinson disease dementia. Owing to the low number of studies we also
      included Parkinson disease. Key terms were used to search the relevant databases.
      Titles and abstracts were screened and potentially relevant articles were
      reviewed in full. References of included studies and relevant reviews were
      searched. The database search returned 2166 results, 46 of which were finally
      included in the systematic review. These studies showed a general increase in
      inflammatory markers in the peripheral blood, most notably interleukin-1beta (IL
      1beta), tumor necrosis factor-alpha, IL-6, and IL-10. Studies examining
      cerebrospinal fluid found IL-1beta, IL-6, and transforming growth factor-beta1 to
      be particularly increased, and interferon-gamma decreased. C-reactive protein
      levels were increased, particularly in Parkinson disease dementia. These results
      provide evidence that LBD is associated with an increased inflammatory response.
      Furthermore, there may be a stronger general inflammatory response in LBD than in
      Parkinson disease, while complex changes occur in the individual cytokines.

PMID- 29016449
TI  - Self-Reported Decline in Everyday Function, Cognitive Symptoms, and Cognitive
      Function in People With HIV.
AB  - BACKGROUND: We determined factors associated with self-reported decline in
      activities of daily living (ADLs) and symptoms of cognitive impairment in HIV
      positive adults in 5 European clinics. METHODS: HIV+ adults underwent
      computerized and pen-and-paper neuropsychological tests and questionnaires of
      cognitive symptoms and ADLs. We considered cognitive function in 5 domains,
      psychosocial factors, and clinical parameters as potentially associated with
      symptoms. Separate regression analyses were used to determine factors associated
      with a decline in ADL (defined as self-reported decline affecting >=2 ADLs and
      attributed to cognitive difficulties) and self-reported frequency of symptoms of
      cognitive impairment. We also estimated the diagnostic accuracy of both
      questionnaires as tests for cognitive impairment. RESULTS: Four hundred forty
      eight patients completed the assessments [mean age 45.8 years, 84% male, 87%
      white, median CD4 count 550 cells/mm, median time since HIV diagnosis 9.9 years,
      81% virologically suppressed (HIV-1 plasma RNA <50 copies/mL)]. Ninety-six
      (21.4%) reported decline in ADLs and attributed this to cognitive difficulties.
      Self-reported decline in ADLs and increased symptoms of cognitive impairment were
      both associated with worse performance on some cognitive tests. There were also
      strong associations with financial difficulties, depressive and anxiety symptoms,
      unemployment, and longer time since HIV diagnosis. Both questionnaires performed
      poorly as diagnostic tests for cognitive impairment. CONCLUSIONS: Patients' own
      assessments of everyday function and symptoms were associated with objectively
      measured cognitive function. However, there were strong associations with other
      psychosocial issues including mood and anxiety disorders and socioeconomic
      hardship. This should be considered when assessing HIV-associated cognitive
      impairment in clinical care or research studies.

PMID- 29016448
TI  - Brief Report: HIV/HBV Coinfection is a Significant Risk Factor for Liver Fibrosis
      in Tanzanian HIV-Infected Adults.
AB  - BACKGROUND: In sub-Saharan Africa, the burden of liver disease associated with
      chronic hepatitis B virus (HBV) and HIV is unknown. We characterized liver
      disease using aspartate aminotransferase-to-platelet ratio index (APRI) and FIB-4
      in patients with HIV, HBV, and HIV/HBV coinfection in Tanzania. METHODS: Using a
      cross-sectional design, we compared the prevalence of liver fibrosis in treatment
      naive HIV monoinfected, HBV monoinfected, and HIV/HBV-coinfected adults enrolled
      at Management and Development for Health (MDH)-supported HIV treatment clinics in
      Dar es Salaam, Tanzania. Risk factors associated with significant fibrosis (APRI
      >0.5 and FIB-4 >1.45) were examined. RESULTS: Two hundred sixty-seven HIV
      infected, 165 HBV-infected, and 63 HIV/HBV-coinfected patients were analyzed [44%
      men, median age 37 (interquartile range 14), body mass index 23 (7)]. APRI and
      FIB-4 were strongly correlated (r = 0.78, P < 0.001, R = 0.61). Overall median
      APRI scores were low {HIV/HBV [0.36 (interquartile range 0.4)], HIV [0.23
      (0.17)], HBV [0.29 (0.15)] (P < 0.01)}. In multivariate analyses, HIV/HBV
      coinfection was associated with APRI >0.5 [HIV/HBV vs. HIV: odds ratio (OR) 3.78
      (95% confidence interval: 1.91 to 7.50)], [HIV/HBV vs. HBV: OR 2.61 (1.26 to
      5.44)]. HIV RNA per 1 log10 copies/mL increase [OR 1.53 (95% confidence interval:
      1.04 to 2.26)] and HBV DNA per 1 log10 copies/mL increase [OR 1.36 (1.15, 1.62)]
      were independently associated with APRI >0.5 in HIV-infected and HBV-infected
      patients, respectively. CONCLUSIONS: HIV/HBV coinfection is an important risk
      factor for significant fibrosis. Higher levels of circulating HIV and HBV virus
      may play a direct role in liver fibrogenesis. Prompt diagnosis and aggressive
      monitoring of liver disease in HIV/HBV coinfection is warranted.

PMID- 29016450
TI  - A NEW DESIGN INTRAOCULAR FOREIGN BODY FORCEPS.

PMID- 29016452
TI  - INTRAOCULAR LENS POSITION IN COMBINED PHACOEMULSIFICATION AND VITREORETINAL
      SURGERY.
AB  - PURPOSE: To assess the decentration and angle of tilt of the intraocular lens
      (IOL) according to the intravitreal tamponade types used in combined
      phacoemulsification and vitreoretinal surgery. METHODS: This prospective and
      randomized clinical study involved 73 eyes of 69 patients who underwent combined
      vitreoretinal surgery. Eyes with intravitreal tamponades formed the study group
      and eyes without intravitreal tamponades formed the control group. The study
      group was further divided into silicone oil and gas tamponade subgroups. Cross
      sectional IOL images were captured using a Pentacam HR (Oculus, Germany) and tilt
      and decentration were calculated with Adobe Photoshop software (Adobe, San Jose,
      CA). RESULTS: The mean angle of tilt and decentration at the vertical meridian
      were significantly higher in both tamponade groups than in the control group (P <
      0.05 for all). No significant difference was observed among the groups regarding
      IOL position parameters at the horizontal meridian (P > 0.05). When comparing the
      silicone oil and gas tamponade subgroups, no significant differences were noted
      on the position of IOL at both meridians (P > 0.05 for all). CONCLUSION:
      Intravitreal tamponades have an important effect on the position of IOL in
      combined vitreoretinal surgery. Silicone oil and gas tamponades may induce
      postoperative tilt and decentration of one-piece acrylic IOLs.

PMID- 29016453
TI  - IN VITRO FLOW ANALYSIS OF NOVEL DOUBLE-CUTTING, OPEN-PORT, ULTRAHIGH-SPEED
      VITRECTOMY SYSTEMS.
AB  - PURPOSE: To analyze the performance and flow characteristics of novel double
      cutting, open-port, 23-, 25-, and 27-gauge ultrahigh-speed vitrectomy systems.
      METHODS: In vitro fluidic measurements were performed to assess the volumetric
      aspiration profiles of several vitrectomy systems in basic salt solution and egg
      white. RESULTS: Double-cutting open-port vitrectomy probes delivered stable
      aspiration flow rates that were less prone to flow variation affected by the
      cutting speed. Increase in cutting frequency to the maximum level resulted in
      flow reduction of less than 10% (0.0%-9.5%). Commercially available 23-, 25-, and
      27-G double-cutting probes exhibited higher egg-white and basic salt solution
      flow rates at all evaluated cut rates, with aspirational efficiencies being 1.1
      to 2.9 times the flow rates of standard single-blade vitrectomy probes of the
      same caliber at the maximum preset vacuum. The highest relative differences were
      observed at faster cut rates. CONCLUSION: The newly introduced double-cutting
      open-port vitrectomy probes delivered stable aspiration flow rates that were less
      prone to flow variation affected by the cutting speed. The fluidic principle of
      constant flow even at the highest cut rates and low vacuum levels might impact
      surgical strategies, especially when performing manipulations close to the
      retina.

PMID- 29016454
TI  - INTRAOCULAR DEXAMETHASONE IMPLANT POSITION IN SITU AND OCULAR HYPERTENSION.
AB  - PURPOSE: To determine the association between the dexamethasone implant position
      in the vitreous cavity and ocular hypertension (OHT). METHODS: Retrospective
      review of patients with at least one intravitreal dexamethasone implant injection
      between 2012 and 2016. Patients who had a minimum follow-up for 6 months and
      documented evidence of the implant position were included in the study. Steroid
      responders, glaucoma patients, vitrectomized eyes, and eyes with liquefied
      vitreous were excluded. Relevant data were collected from patient charts. Three
      positions (P1, P2, and P3) were identified: P1 (in contact with the pars
      plana/ciliary body region), P2 (anterior to vortex veins), and P3 (posterior to
      vortex veins). Ocular hypertension was defined as absolute intraocular pressure >
      25 mmHg and/or intraocular pressure rise > 10 mmHg. The relationship between
      implant position and intraocular pressure rise after factoring in other
      characteristics was the outcome measure. Appropriate statistical analysis was
      performed. RESULTS: A total of 377 patients (432 eyes; 257 males; 677 injections)
      were eligible for analysis. The median age was 57.24 (+/-6.32) years. Eighty
      eight eyes had OHT. Of these, 54 eyes had the implant in P1. P1 was associated
      with high intraocular pressure response (>15 mmHg; P = 0.004) and early (<15
      days) onset OHT (r = 0.84, P < 0.001). CONCLUSION: Anterior position of
      dexamethasone implant in situ increases the risk of OHT.

PMID- 29016451
TI  - CONCURRENT IDIOPATHIC MACULAR TELANGIECTASIA TYPE 2 AND CENTRAL SEROUS
      CHORIORETINOPATHY.
AB  - PURPOSE: To describe cases presenting with features of idiopathic macular
      telangiectasia (MacTel) Type 2 and central serous chorioretinopathy (CSC).
      METHODS: Databases from four tertiary retina centers were searched for cases
      copresenting CSC and MacTel Type 2. RESULTS: Five cases were identified (4 men, 1
      woman; mean age: 67.2 years). Four patients were referred for chronic or
      nonresolving CSC, and the diagnosis of MacTel Type 2 was made based on multimodal
      imaging findings. One patient had advanced MacTel Type 2, and developed acute
      CSC. Regarding the MacTel Type 2 findings, all subjects presented perifoveal
      telangiectasia on fluorescein angiography, and four subjects showed intraretinal
      cavitations typical of MacTel Type 2 on optical coherence tomography, in one or
      both eyes. Regarding the CSC findings, fluorescein angiography identified focal
      or extended retinal pigment epithelium alteration in all eyes, and an active
      leakage in two eyes. Indocyanine green angiography showed choroidal vascular
      hyperpermeability in four subjects. On optical coherence tomography, pigment
      epithelial detachments were detected in five eyes (four subjects), and foveal
      detachments were present in five eyes (three subjects), which spontaneously
      resolved (two eyes), responded to photodynamic therapy (two eyes), or persisted
      (one eye). Mean choroidal thickness was 402 +/- 99 MUm. CONCLUSION: The
      codiagnosis of CSC and MacTel Type 2 should be considered in atypical
      presentations associating features from both disorders.

PMID- 29016455
TI  - Reply.

PMID- 29016456
TI  - NEW ULTRA-WIDE-FIELD ANGIOGRAPHIC GRADING SCHEME FOR RADIATION RETINOPATHY AFTER
      IODINE-125 BRACHYTHERAPY FOR UVEAL MELANOMA.
AB  - PURPOSE: Radiation retinopathy remains incompletely characterized and may cause
      severe vision loss. Ultra-wide-field fluorescein angiography provides a pan
      fundus view of vascular alterations caused by radiation treatment and may predict
      visual and ocular outcomes. We have developed a grading scheme to describe pan
      fundus severity and to predict the progression of radiation retinopathy in
      patients treated for uveal melanoma with iodine-125 brachytherapy. METHODS: A
      retrospective review of patients treated with standard iodine-125 brachytherapy
      for uveal melanoma at the Ophthalmic Oncology Center at the University of
      California, Los Angeles, who had undergone both baseline and postbrachytherapy
      ultra-wide-field fluorescein angiography. A grading scheme was devised based on
      observations of vascular leakage, retinal perfusion status, and retinal
      proliferation. The correlation of grade severity with patient characteristics,
      tumor features, visual acuity, optical coherence tomography findings, and
      neovascular glaucoma was measured with chi-square and one-way analysis of
      variance analyses. RESULTS: Sixty-seven patients were identified for review.
      Consistent wide-field angiographic patterns after brachytherapy were observed and
      graded as follows: Grade 0: normal; Grade 1: late foveal leakage; Grade 2: late
      peripheral leakage; Grade 3: presence of nonperfusion; and Grade 4: retinal
      neovascularization. Six eyes (8.9%) were Grade 0; 16 (23.8%) were Grade 1; 25
      (37.3%) were Grade 2; 16 (23.4%) were Grade 3; and 4 (6.0%) were Grade 4. Higher
      grade radiation severity correlated significantly with duration of follow-up (P <
      0.02); younger age (P = 0.035); worse visual acuity (P = 0.001); cystoid macular
      edema or atrophy on optical coherence tomography (P < 0.0001); and neovascular
      glaucoma (P = 0.003). CONCLUSION: Wide-field fluorescein angiography revealed
      distinct fundus-wide patterns of vascular damage, which were progressive in
      nature in eyes treated with iodine-125 brachytherapy for uveal melanoma and
      correlated with signs of progressive vascular injury. This grading scheme may
      have prognostic value to predict the progression of radiation retinopathy and to
      prognosticate visual outcomes in patients undergoing brachytherapy.

PMID- 29016457
TI  - OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN GEOGRAPHIC ATROPHY.
AB  - PURPOSE: To analyze choriocapillaris (CC) vessel density (VD) around geographic
      atrophy (GA) secondary to non-neovascular dry age-related macular degeneration
      using optical coherence tomography angiography. METHODS: We compared CC VD
      surrounding GA margin (500 MUm radius) with control CC (outside GA margin) in a
      consecutive series of GA patients presenting between August 2016 and February
      2017 at the Medical Retina and Imaging Unit of University Vita-Salute, IRCCS
      Ospedale San Raffaele in Milan. Images were obtained through thresholding and
      binarization. We also compared the CC VD in a sample area of 500 MUm * 500 MUm
      surrounding GA margin rated as hyperautofluorescent on fundus autofluorescence to
      a similar area rated as isoautofluorescent. RESULTS: Fifty eyes of 29 patients
      (19 women and 10 men; mean age 77 +/- 6 years) with mean GA area of 9.43 +/- 5.08
      mm and mean subfoveal choroidal thickness of 164 +/- 73 MUm were included.
      Choriocapillaris VD surrounding GA margin as detected by optical coherence
      tomography angiography revealed a significant impairment compared with control CC
      outside GA margin (0.317 +/- 0.083 vs. 0.461 +/- 0.054, P < 0.001), which was
      even greater in patients with foveal involvement (P = 0.013). Furthermore, mean
      VD in hyperautofluorescent areas was significantly lower compared with
      isoautofluorescent areas (0.242 +/- 0.112 vs. 0.327 +/- 0.130, P = 0.001). A
      positive correlation was disclosed between VD surrounding GA margin and subfoveal
      choroidal thickness (r = 0.332, P = 0.019). CONCLUSION: Optical coherence
      tomography angiography discloses CC impairment surrounding GA margin. Such CC
      impairment at GA margin seems to precede retinal pigment epithelium alterations
      at fundus autofluorescence. Optical coherence tomography angiography could be a
      new valuable tool for detecting CC alterations and to evaluate potential
      therapeutic responses in clinical studies.

PMID- 29016459
TI  - CHOROIDAL STRUCTURAL CHANGES AND VASCULARITY INDEX IN STARGARDT DISEASE ON SWEPT
      SOURCE OPTICAL COHERENCE TOMOGRAPHY.
AB  - PURPOSE: To evaluate structural changes in the choroid of patients with Stargardt
      disease using swept source optical coherence tomography scans. METHODS: A
      retrospective comparison cohort study was conducted on 39 patients with Stargardt
      disease, and on 25 age and gender matched-healthy controls. Subfoveal choroidal
      thickness (SFCT) was computed from the swept source optical coherence tomography
      machine, and the scans were binarized into luminal area and stromal areas, which
      were then used to derive choroidal vascularity index (CVI). Choroidal vascularity
      index and SFCT were analyzed independently using linear mixed effects model.
      RESULTS: There was no significant difference in SFCT between the 2 groups (347.20
      +/- 13.61 MUm in Stargardt disease vs. 333.09 +/- 18.96 MUm in the control group,
      P = 0.548). There was a significant decrease in the CVI among eyes with Stargardt
      disease as compared with the normal eyes (62.51 +/- 0.25% vs. 65.45 +/- 0.29%, P
      < 0.001). There was a negative association between visual acuity and CVI
      (correlation coefficient = -0.75, P < 0.001) and a positive association between
      visual acuity and SFCT (correlation coefficient = 0.21, P = 0.035). CONCLUSION:
      Choroidal vascularity index appears to be a more robust tool compared with SFCT
      for choroidal changes in Stargardt disease. Choroidal vascularity index can
      possibly be used as a surrogate marker for disease monitoring. A decrease in CVI
      was associated with a decrease in visual function in eyes with Stargardt disease.

PMID- 29016458
TI  - QUANTITATIVE ANALYSIS OF HYPERAUTOFLUORESCENT RINGS TO CHARACTERIZE THE NATURAL
      HISTORY AND PROGRESSION IN RPGR-ASSOCIATED RETINOPATHY.
AB  - PURPOSE: Quantitative analysis of hyperautofluorescent rings and progression in
      subjects with retinitis pigmentosa associated with retinitis pigmentosa GTPase
      regulator (RPGR) gene mutations. METHODS: Prospective observational study of 46
      subjects. Ring area, horizontal and vertical diameter measurements taken from
      outer and inner ring borders. Intraobserver repeatability, baseline measurements,
      progression rates, interocular symmetry, and association with age and genotype
      were investigated. RESULTS: Baseline ring area was 11.8 +/- 13.4 mm and 11.4 +/-
      13.2 mm for right and left eyes, respectively, with very strong interocular
      correlation (r = 0.9398; P < 0.0001). Ring area constriction was 1.5 +/- 2.0
      mm/year and 1.3 +/- 1.9 mm/year for right and left eyes, respectively, with very
      strong interocular correlation (r = 0.878, P < 0.0001). Baseline ring area and
      constriction rate correlated negatively with age (r = -0.767; P < 0.0001 and r = 
      0.644, P < 0.0001, respectively). Constriction rate correlated strongly with
      baseline area (r = 0.850, P < 0.0001). Age, but not genotype, exerted a
      significant effect on constriction rates (P < 0.0001), with greatest rates of
      progression seen in younger subjects. An exponential decline overall was found.
      CONCLUSION: This study provides disease-specific baseline values and progression
      rates together with a repeatability assessment of fundus autofluorescence
      metrics. Our findings can guide future treatment trials and contribute to the
      clinical care of patients with RPGR-associated retinitis pigmentosa.

PMID- 29016460
TI  - TREFOIL FACTOR FAMILY 1 EXPRESSION CORRELATES WITH CLINICAL OUTCOME IN PATIENTS
      WITH RETINOBLASTOMA.
AB  - PURPOSE: Correlation of trefoil factor family 1 (TFF1) expression in
      retinoblastoma tumors with different clinical parameters to evaluate a potential
      involvement of TFF1 in tumor development and progression. METHODS: A
      representative cohort of 59 enucleated eyes from individual patients with
      retinoblastoma was analyzed for its TFF1 expression profile by immuno staining
      and real-time PCR. Trefoil factor family 1 expression was correlated with
      demographics, laterality, tumor-node-metastasis stage, International
      Classification of Retinoblastoma, tumor differentiation level, and treatment.
      RESULTS: According to our analysis, increased TFF1 expression significantly
      correlates with unilateral tumors diagnosed in older children and with poorly
      differentiated tumors and higher tumor-node-metastasis stages. CONCLUSION: This
      retrospective study reveals that unilateral tumors at a higher clinical tumor
      node-metastasis stage and poorly differentiated tumor cells express significantly
      higher levels of TFF1 than those of differentiated tumors at lower tumor-node
      metastasis stages. Besides, TFF1 expression correlates with the age of the
      patients at the time of tumor diagnosis. Our data indicate that TFF1 expression
      levels are potentially useful additional markers in the classification of tumor
      staging and prognosis of patients with retinoblastoma.

PMID- 29016462
TI  - The Medical Futility Experience of Nurses in Caring for Critically Ill Patients.
AB  - BACKGROUND: Medical futility is a key bioethical concern. In Taiwan, policymakers
      tend to provide care standards and evaluation guidelines for critically ill and
      terminal patients whose treatment is medically futile. However, the current
      status of medical futility for critically ill patients is inadequate, and no
      consensus currently exists on the definition of medical futility. PURPOSE: The
      aim of this study was to understand the medical futility experiences of intensive
      care nurses. METHODS: This qualitative research adopted a phenomenological
      perspective and was conducted in a medical center and a regional hospital in
      Central Taiwan. Eight nurses with at least 1 year of nursing tenure who were
      serving in the intensive care unit were recruited. Purposive and snowball
      sampling methods were used to conduct one-on-one in-depth interviews. Each of the
      tape-recorded interviews was transcribed before data analysis. RESULTS: The
      research results found four themes, including (a) definitions of medical futility
      and types of patients, (b) considerations of medical futility, (c) the occurrence
      of medical futility, and (d) nurses' responses to medical futility. The
      participants indicated that medical futility refers to the point at which the
      continued provision of treatment does not evidently ease the disease condition of
      a patient or improve his or her quality of life or when life-sustaining treatment
      is provided to patients to facilitate the process of death. CONCLUSIONS: This
      study revealed that the major challenge in clinical cases of medical futility is
      for physicians, nurses, and patients to communicate effectively together during
      times of rapid and unanticipated change in patient condition. Thus, events of
      medical futility may be preventable. Past cases of medical futility involving
      critically ill patients may serve as references for guiding clinical care,
      education, and related policy formulation.

PMID- 29016461
TI  - Social learning pathways in the relation between parental chronic pain and daily
      pain severity and functional impairment in adolescents with functional abdominal
      pain.
AB  - Having a parent with chronic pain (CP) may confer greater risk of persistence of
      CP from childhood into young adulthood. Social learning, such as parental
      modeling and reinforcement, represents one plausible mechanism for the
      transmission of risk of CP from parents to offspring. Based on a 7-day pain diary
      in 154 pediatric patients with functional abdominal CP, we tested a model in
      which parental CP predicted adolescents' daily average CP severity and functional
      impairment (distal outcomes) via parental modeling of pain behaviors and parental
      reinforcement of adolescent's pain behaviors (mediators) and adolescents'
      cognitive appraisals of pain threat (proximal outcome representing adolescents'
      encoding of parents' behaviors). Results indicated significant indirect pathways
      from parental CP status to adolescent average daily pain severity (b = 0.18, SE =
      0.08, 95% confidence interval: 0.04-0.31, P = 0.03) and functional impairment (b
      = 0.08, SE = 0.04, 95% confidence interval: 0.02-0.15, P = 0.03) over the 7-day
      diary period via adolescents' observations of parent pain behaviors and
      adolescent pain threat appraisal. The indirect pathway through parental
      reinforcing responses to adolescents' pain did not reach significance for either
      adolescent pain severity or functional impairment. Identifying mechanisms of
      increased risk of pain and functional impairment in children of parents with CP
      ultimately could lead to targeted interventions aimed at improving functioning
      and quality of life in families with CP. Parental modeling of pain behaviors
      represents a potentially promising target for family-based interventions to
      ameliorate pediatric CP.

PMID- 29016463
TI  - A Preliminary Study of the Effects of a Multitheory-Driven Intervention in Adults
      With Prediabetes Mellitus.
AB  - BACKGROUND: Prediabetes mellitus (pre-DM) is an important predictive indicator of
      Type 2 diabetes. A person with pre-DM is eight times more likely to develop
      diabetes than a person without pre-DM. Prior research suggests that proactive
      interventions may delay the progression of this disease and reduce the rate of
      disease development. PURPOSE: The purposes of this preliminary study were to
      develop a multitheory-driven lifestyle intervention protocol for adults with pre
      DM and to evaluate its feasibility and impacts on knowledge regarding pre-DM,
      dietary behaviors, and physical activity (primary outcomes) as well as to
      describe the disease progression indicators (secondary outcomes). METHODS: A
      single-group, longitudinal study design was used. Thirty-nine participants were
      included in the analysis. A generalized estimating equation model was used to
      determine the trends in changes in the outcomes. All of the participants
      underwent testing at baseline (T0) and at 3 (T1), 6 (T2), and 12 (T3) months
      after the 4-week lifestyle intervention. RESULTS: There were significantly
      increasing trends for each study parameter (Pre-DM Knowledge Assessment Form-12,
      p < .01; Dietary Behavior Scale, p < .01) and significantly positive changes in
      body weight (p < .01), body mass index (p < .01), fasting glucose level (p <
      .01), and glycated hemoglobin level (p < .01) over the 12-month study period.
      CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study supports the feasibility of the
      developed multitheory-driven lifestyle intervention protocol and suggests that
      its application may improve the effectiveness of diabetes prevention programs in
      clinical settings. Further randomized controlled trials are needed.

PMID- 29016464
TI  - Perceptions of Diabetes Self-Care Management Among Older Singaporeans With Type 2
      Diabetes: A Qualitative Study.
AB  - BACKGROUND: Given the global shift in aging populations and the associated
      increasing prevalence of diabetes, it is critical to explore new approaches in
      diabetic self-care management. In Singapore, what has been overlooked to date is
      an in-depth, contextually based examination of the needs, expectations, and
      barriers faced in self-care management by older adults with Type 2 diabetes.
      PURPOSE: This study aimed to explore the experiences of older Singaporeans with
      Type 2 diabetes in diabetes self-care management to understand their perceived
      needs, expectations, and barriers associated with their diabetes self-care
      management. METHODS: A descriptive qualitative approach using focus group
      discussions was adopted. Purposive sampling was used to recruit older adults with
      Type 2 diabetes from Singapore's three main ethnic groups, namely, Chinese,
      Malay, and Indian, through the diabetes centers of two hospitals. Four focus
      groups, including two groups of Chinese, one group of Malays, and one group of
      Indians, were conducted. Thematic analysis was used to analyze the data set for
      emerging themes that relate to the experiences of participants with diabetes self
      care management. RESULTS: The four major themes related to the experiences of
      participants with diabetes self-care management that emerged were as follows: (a)
      "Diabetes is genetic, destined, and not serious; complication, let it come"; (b)
      "Diabetes self-care is difficult"; (c) "I don't know diabetes"; and (d) "Doctor
      and nurses are important facilitators of self-care management."
      CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Findings have important implications in
      Singapore as well as in other Asian countries where populations are also aging
      and diabetes prevalence is increasing. The findings provide new culturally
      focused insights for clinical patient education within the Southeast Asian
      context to improve diabetes self-care management of older adults.

PMID- 29016465
TI  - Information Reception and Expectations Among Hospitalized Elderly Patients in
      Taiwan: A Pilot Study.
AB  - BACKGROUND: Communicating with patients, especially geriatric patients, is a
      challenge for medical professionals. Medical message receiving and expectations
      among hospitalized elderly patients have not been studied. PURPOSE: The aim of
      this study was to explore medical message receiving and expectations concerning
      medical information among hospitalized elderly patients in Taiwan. METHODS: A
      descriptive study design was used. Convenience sampling was applied, and the
      research was conducted in a geriatric ward in a medical center in southern
      Taiwan. Patients were recruited who were 65 years or older and capable of verbal
      communication. Data were collected using a self-developed semistructured
      questionnaire. For each participant, data were collected in one regular ward
      round. The messages of the physician were recorded. During the first and fourth
      hours after the ward round, the researcher collected the medical messages that
      were conveyed by the physician in the ward round and that could be repeated by
      the patients. Open-ended questions were used to collect data about patient
      expectations of medical messages during the first hour after the ward round.
      Quantitative data were analyzed using descriptive statistics, and qualitative
      data were analyzed using content analysis. RESULTS: Thirty patients participated
      in this study. All of the participants remembered the visit of the physician.
      Seventeen participants (56.6%), however, could not repeat the messages, and the
      total message repetition rate was 17.8% at the first hour after the ward round.
      By the fourth hour, the message repetition rate fell to 8.9%. Furthermore, three
      participants (10%) reported messages incorrectly. Participants reported the
      importance and necessity of physicians conveying medical messages. "Desire to
      know the reasons for discomfort" and "discharge date" were the messages most
      expected by the participants. CONCLUSIONS: This study suggests that most
      hospitalized elderly patients cannot repeat medical messages that are conveyed by
      their physicians. Written materials and the involvement of principal caregivers
      in the medical informing process may be necessary. Besides, before providing
      medical information, medical professionals should be cognizant of the key
      concerns of their patients.

PMID- 29016466
TI  - Comparing the Effects of Simulation-Based and Traditional Teaching Methods on the
      Critical Thinking Abilities and Self-Confidence of Nursing Students.
AB  - BACKGROUND: Critical thinking and self-confidence are imperative to success in
      clinical practice. Educators should use teaching strategies that will help
      students enhance their critical thinking and self-confidence in complex content
      such as electrocardiogram interpretation. Therefore, teaching electrocardiogram
      interpretation to students is important for nurse educators. PURPOSE: This study
      compares the effect of simulation-based and traditional teaching methods on the
      critical thinking and self-confidence of students during electrocardiogram
      interpretation sessions. METHODS: Thirty undergraduate nursing students
      volunteered to participate in this study. The participants were divided into
      intervention and control groups, which were taught respectively using the
      simulation-based and traditional teaching programs. All of the participants were
      asked to complete the study instrumentpretest and posttest to measure their
      critical thinking and self-confidence. RESULTS: Improvement was observed in the
      control and experimental groups with respect to critical thinking and self
      confidence, as evidenced by the results of the paired samples t test and the
      Wilcoxon signed-rank test (p < .05). However, the independent t test and Mann
      Whitney U test indicate that the difference between the two groups was not
      significant (p > .05). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study
      evaluated an innovative simulation-based teaching method for nurses. No
      significant differences in outcomes were identified between the simulator-based
      and traditional teaching methods, indicating that well-implemented educational
      programs that use either teaching method effectively promote critical thinking
      and self-confidence in nursing students. Nurse educators are encouraged to design
      educational plans with clear objectives to improve the critical thinking and self
      confidence of their students. Future research should compare the effects of
      several teaching sessions using each method in a larger sample.

PMID- 29016467
TI  - The Development and Psychometric Testing on Psychiatric Nurses of a Nurse Case
      Management Competence Scale in Taiwan.
AB  - BACKGROUND: Case management is a complex process involving multiple activities.
      It is vital that nurses are competent in all related tasks for case management. A
      competence scale is a valuable tool for assessing task-related competency.
      PURPOSE: The aims of this study were to examine the reliability and validity of
      an assessment scale for nurse case management competence and to use this scale to
      assess the current competency of nurses. METHODS: A nurse case management
      competence scale was developed in three stages: (a) selection of assessment items
      according to standards of practice for case management and literature review, (b)
      determination of content validity using the Delphi technique with a panel of
      experts, and (c) psychometric testing of the developed competence scale using a
      cross-sectional design. Convenience sampling was used to recruit psychiatric
      nurses at seven psychiatric centers in Taiwan to complete the scale anonymously.
      An exploratory factor analysis was performed to analyze construct validity.
      Discriminant validity, internal consistency, and 2-week test-retest reliability
      were also examined. RESULTS: Two hundred eighty-five psychiatric nurses completed
      an assessment scale comprising 18 items (originally 25 items). The content
      validity index reached 0.96 after the Delphi technique was applied twice in the
      expert panel. Seventy-eight percent of the total variance was explained by two
      dimension factors: coordination facilitation competence and direct care
      competence. Participants who had undertaken case management courses had superior
      case management ability compared with those who had not, indicating that the
      scale possesses excellent discriminant validity. Cronbach's alpha and the test
      retest results showed excellent reliability. Of the two competence factors,
      direct care competence (3.03) was better than coordination facilitation
      competence (2.81). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: There is a dearth of
      studies investigating the development and psychometric testing of case management
      competence scales. The results of this study provide evidence to support the
      reliability and validity of the developed case management competence scale among
      Taiwanese psychiatric nurses. It is a reliable and valid assessment instrument
      that may help identify educational needs and improve the case management
      competencies of nurses.

PMID- 29016468
TI  - A Systematic Review of Reminiscence Therapy for Older Adults in Taiwan.
AB  - BACKGROUND: Population aging is an increasing phenomenon in many countries around
      the world. It has been estimated that more than one quarter of all older adults
      experience a mental or neurological disorder or disease such as dementia,
      depression, anxiety, and substance abuse. Reminiscence is a popular treatment for
      enhancing well-being in older adults. Previous studies have shown that
      reminiscence therapy improves the cognitive functions, behaviors, and other
      psychosocial outcomes in older adult patients. The themes and materials that are
      used in reminiscence treatments for the older adults in Taiwan differ from those
      used in other countries because of Taiwan's unique historical background and
      culture. PURPOSE: The main purpose of the current study was to review
      systematically the application and outcomes of reminiscence therapy in Taiwan.
      METHOD: The terms "reminiscence," "dementia," "Alzheimer's disease," and "Taiwan"
      were used in an Integrated Resources Search that was conducted at National Taiwan
      Normal University. Sixteen articles were systematically reviewed using a
      synthesis of two matrices of experimental designs and intervention designs.
      RESULT: Reminiscence group sizes ranged between 7 and 12 participants, session
      frequencies were all once a week for periods lasting between 4 and 16 weeks, and
      session durations ranged from 30 minutes to 2 hours. The memories of the
      participants were stimulated using materials dating from their youth such as
      Taiwanese folk songs, toys, photos, radio programs, newspapers, and food and
      drinks. In terms of research methodology, most of the studies that were reviewed
      used quasi-experimental designs without random assignment or control group due to
      sample size. A minority of the reviewed studies applied the randomized controlled
      treatment method. Only a few of the studies evaluated indicators in pretest,
      posttest, and follow-up periods. The results of these studies identified several
      benefits of reminiscence therapy in Taiwanese older adults, including
      improvements in cognitive function, anxiety, depressive symptoms, self-esteem,
      life satisfaction, and personal interaction. CONCLUSIONS: Reminiscence is a good
      noninvasive treatment for the prevention and treatment of mental diseases in
      Taiwanese older adults. Furthermore, reminiscence promotes mental health in older
      adults. Finally, this study provides recommendations for further study and
      clinical application of reminiscence therapy in Taiwan.

PMID- 29016469
TI  - Relationship Between Lifestyles That Promote Health and Quality of Life in
      Patients With Chronic Schizophrenia: A Cross-Sectional Study.
AB  - BACKGROUND: Over the last few decades, an increasing number of studies have
      examined quality of life in patients with chronic schizophrenia. However, little
      research has addressed the relationship between lifestyles that promote health
      and quality of life issues in these patients. PURPOSE: The aim of this study was
      to investigate the relationships between lifestyles that promote health and
      quality of life in patients with chronic schizophrenia. METHODS: A cross
      sectional study design was used. The study was conducted at 10 hospital-based
      psychiatric rehabilitation units in northern Taiwan. In total, 357 participants
      completed the World Health Organization Quality of Life-BREF and the Health
      Promoting Lifestyle Profile. This study examined the relationships among the six
      domains of the Health-Promoting Lifestyle Profile and the four domains of the
      Quality of Life-BREF using canonical correlation analysis. Data collection
      occurred between April 2013 and April 2014. RESULTS: The results of the canonical
      correlation analysis showed that the Health-Promoting Lifestyle Profile domains
      of nutrition, health responsibility, self-actualization, interpersonal support,
      exercise, and stress management were significantly related to the Quality of Life
      BREF results, specifically in the physical, psychological, and social
      relationships and environment domains. Two canonical correlations were identified
      (the canonical correlation coefficients were .622 and .317), which showed that
      38.6% of the variance in lifestyles that promote health and quality of life was
      shared. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results of this study may be
      useful to practitioners who are responsible for lifestyles that promote health
      and quality of life issues in patients with chronic schizophrenia.

PMID- 29016471
TI  - An Update on the Diagnosis, Grading, and Staging of Appendiceal Mucinous
      Neoplasms.
AB  - Despite advances in our understanding of appendiceal mucinous neoplasms and their
      relationship to the pseudomyxoma peritonei syndrome, the classification of
      mucinous tumors of the appendix is still confusing. This review will provide an
      update on the various classification systems that have been recently proposed for
      appendiceal mucinous neoplasia, with a particular emphasis on how to handle and
      report the histologic findings for these tumors using the newly published
      Peritoneal Surface Oncology Group International (PSOGI) and American Joint
      Committee on Cancer (AJCC) eighth edition guidelines. A simplified approach to
      diagnostic reporting of appendiceal mucinous neoplasms based on the 3-tier AJCC
      grading scheme is detailed and specific criteria for assessing grade in
      appendiceal mucinous neoplasia will be outlined. In addition, histologic mimics
      of appendiceal mucinous neoplasia and how to distinguish these mimics from
      mucinous neoplasia will be discussed. Finally, despite improvements in diagnostic
      terminology, significant challenges in classifying appendiceal mucinous neoplasia
      persist and diagnostic strategies will be detailed to assist practicing
      pathologists in these challenging scenarios.

PMID- 29016470
TI  - Efficacy of branched-chain amino acid supplementation and walking exercise for
      preventing sarcopenia in patients with liver cirrhosis.
AB  - BACKGROUND/AIM: Sarcopenia is recognized as a condition related to quality of
      life and prognosis in patients with chronic liver disease, although no useful
      strategy for improving muscle volume and strength has been established. Here, we
      evaluated the efficacy of supplementation with branched-chain amino acid (BCAA)
      administration and walking exercise. PATIENTS AND METHODS: From December 2015 to
      July 2016, 33 Japanese outpatients with liver cirrhosis were enrolled (median: 67
      years, HCV : HBV : alcohol : others=26 : 2 : 2 : 3, male : female=13 : 20, Child
      Pugh A : B=30 : 3). None had a history of BCAA supplementation. After calculating
      the average number of daily steps using a pedometer for a 2-3-week period, BCAA
      supplementation (protein 13.5 g, 210 kcal/day) as a late evening snack and
      walking exercise (additional 2000 steps/day prescribed) were started. Body
      composition including muscle volume was analyzed using a bioelectrical impedance
      analysis method, and serological data and muscle strength (leg, handgrip) were
      evaluated at enrollment, and then 1, 2, and 3 months after starting the protocol.
      RESULTS: The median average number of daily steps was 3791 (interquartile range:
      2238-5484). The average period of BCAA supplementation was 2.7+/-0.7 months.
      During the period from enrollment to 3 months after starting the protocol, HbA1c
      and NH3 were not significantly changed, whereas the BCAA/tyrosine ratio improved
      (4.3+/-1.35 to 5.24+/-2.04, P=0.001). In addition, the ratios for average daily
      steps (1.595, P=0.02) as well as muscle volume, leg strength, and handgrip
      strength (1.013, 1.110, and 1.056, respectively; all P<0.01) were increased at 3
      months. CONCLUSION: BCAA supplementation and walking exercise were found to be
      effective and easily implemented for improving muscle volume and strength in
      liver cirrhosis patients.

PMID- 29016472
TI  - Longitudinal Changes in Body Composition Throughout Successive Seasonal Phases
      Among Canadian University Football Players.
AB  - Kim, J, Delisle-Houde, P, Reid, RER, and Andersen, RE. Longitudinal changes in
      body composition throughout successive seasonal phases among Canadian university
      football players. J Strength Cond Res 32(8): 2284-2293, 2018-The purpose of this
      study was to assess changes in body composition during seasonal phases of the
      training year among Canadian Inter-University Sport (CIS) football players. Forty
      university football players were assessed for anthropometry, total body
      composition, regional body composition, and central adiposity over a 7-month
      period including the summer off-season and the in-season. Baseline testing
      occurred in April, before the summer off-season, and follow-ups were completed
      before training camp, at the beginning of August, and following the in-season, at
      the beginning of November. Linemen had the greatest tissue percent fat (25.98 +/-
      6.56%) at baseline, significantly (p < 0.01) greater than big skill (18.69 +/-
      3.97%) and followed by skill (14.35 +/- 3.39%) who were significantly (p < 0.01)
      leaner than both other groups. Skill players significantly increased fat mass
      (0.98 +/- 0.30 kg, p <= 0.05) and waist-to-hip ratio (0.02 +/- 0.01, p <= 0.05)
      during the in-season, and linemen increased visceral fat mass from April to
      November (0.20 +/- 0.06 kg, p <= 0.01). All players significantly (-1.26 +/- 0.30
      kg, p = 0.001) decreased lean mass during the in-season. All groups significantly
      increased bone mineral content during the summer off-season (p <= 0.05). There
      was also a significant time * summer training location interaction (p <= 0.05)
      for fat mass with athletes who remained on campus during summer months gaining
      the least amount of adiposity. Body composition and central adiposity seem to
      change differentially among positional groups across the annual training season.

PMID- 29016473
TI  - Effects of low-load, higher-repetition versus high-load, lower-repetition
      resistance training not performed to failure on muscle strength, mass, and echo
      intensity in healthy young men: a time-course study.
AB  - The aim of the present study was to compare the effects of low-load, higher
      repetition training (LLHR) with those of high-load, lower-repetition training
      (HLLR) on muscle strength, mass, and echo intensity in healthy young men. Fifteen
      healthy men (age, 23.1 +/- 2.6 years) were randomly assigned to one of the two
      groups: LLHR or HLLR group. Resistance training on knee extensor muscles was
      performed 3 days per week for 8 weeks. One-repetition maximum (1RM) strength,
      maximum isometric strength, muscle thickness and muscle echo intensity on
      ultrasonography of the rectus femoris muscle were assessed every 2 weeks.
      Analysis of variance showed no significant group * time interaction, and only a
      significant main effect of time was observed for all variables. The 8-week
      resistance training increased 1RM, maximum isometric muscle strength, and muscle
      thickness by 36.2%-40.9%, 24.0%-25.5%, and 11.3%-20.4%, respectively, whereas it
      decreased echo intensity by 8.05%-16.3%. Significant improvements in muscle
      strength, thickness, and echo intensity were observed at weeks 2, 4, and 8,
      respectively. The lack of difference in time-course changes between LLHR and HLLR
      programs suggests that low-load training can exert similar effects on muscle mass
      and characteristics as high-load training by increasing the number of
      repetitions, even when not performed to failure.

PMID- 29016474
TI  - Cardiac Autonomic and Blood Pressure Responses to an Acute Bout of Kettlebell
      Exercise.
AB  - Kettlebell (KB) training has become an extremely popular exercise program for
      improving both muscle strength and aerobic fitness. However, the cardiac
      autonomic modulation and blood pressure (BP) responses induced by an acute KB
      exercise session are currently unknown. Understanding the impact of this exercise
      modality on the post-exercise autonomic modulation and BP would facilitate
      appropriate exercise prescription in susceptible populations. The present study
      evaluated the effects of an acute session of KB exercise on heart rate
      variability (HRV) and BP responses in healthy individuals. Seventeen (M=10, F=7)
      healthy subjects completed either a KB or non-exercise control trial in
      randomized order. HRV and BP measurements were collected at baseline, 3, 10 and
      30 min after each trial. There were significant increases (P < 0.01) in heart
      rate, markers of sympathetic activity (nLF) and sympathovagal balance (nLF/nHF)
      for 30 min after the trial KB trial, while no changes from baseline were observed
      after the control trial. There were also significant decreases (P < 0.01) in
      markers of vagal tone (RMMSD, nHF) for 30 min as well as (P < 0.01) systolic BP
      and diastolic BP at 10 and 30 min after the trial KB trial while no changes from
      baseline were observed after the control trial. Our findings indicate that KB
      exercise increases sympathovagal balance for 30 min post-intervention which is
      concurrent with an important hypotensive effect. Further research is warranted to
      evaluate the potential clinical application of KB training in populations that
      might benefit from post-exercise hypotension, such as hypertensives.

PMID- 29016475
TI  - Relationship between Physiological Off-Ice Testing, On-Ice Skating, and Game
      Performance in Division I Women's Ice Hockey Players.
AB  - The purpose was to identify off-ice testing variables that correlate to skating
      and game performance in Division I collegiate women ice hockey players. Twenty
      female, forward and defensive players (19.95 +/- 1.35 yr) were assessed for
      weight, height, percent fat mass (%FAT), bone mineral density, predicted one
      repetition maximum (RM) absolute and relative (REL%) bench press (BP) and hex bar
      deadlift (HDL), lower body explosive power, anaerobic power, countermovement
      vertical jump (CMJ), maximum inspiratory pressure (MIP), and on-ice repeated
      skate sprint (RSS) performance. The on-ice RSS test included 6 timed 85.6 m
      sprints with participants wearing full hockey equipment; fastest time (FT),
      average time (AT) and fatigue index (FI) for the first length skate (FLS; 10 m)
      and total length skate (TLS; 85.6 m) were used for analysis. Game performance was
      evaluated with game statistics: goals, assists, points, plus-minus, and shots on
      goal (SOG). Correlation coefficients were used to determine relationships.
      Percent fat mass was positively correlated (p < 0.05) with FLS-FI and TLS-AT; TLS
      FT was negatively correlated with REL%HDL; BP-RM was negatively correlated with
      FLS-FT and FLS-AT; MIP positively correlated with assists, points, and SOG; FLS
      AT negatively correlated with assists. Game performance in women ice hockey
      players may be enhanced by greater MIP, repeat acceleration ability, and mode
      specific training. Faster skating times were associated with lower %FAT. Skating
      performance in women ice hockey players may be enhanced by improving body
      composition, anaerobic power, and both lower and upper body strength in off-ice
      training.

PMID- 29016476
TI  - Effects of in-season circuit training on physical abilities in male handball
      players.
AB  - This study analyzed the effects of a resistance-type circuit training program
      (RCT) (30-35 minutes, performed twice a week for 10 weeks) on male handball
      players. Twenty-two males were divided into experimental (E; age 20.3 +/- 0.5
      years) and control groups (C; age 20.1+/- 0.5 years). Measures before and after
      RCT included squat (SJ) and countermovement jumps (CMJ), one repetition maximum
      (1-RM) ofbench press, pull-over and back half-squats, throwing velocity (a 3-step
      throw with run (RT), and a jump throw (JT)), repeated-sprint ability (six 2 x 15
      m shuttle sprints with recording of best time for a single trial), anthropometric
      estimates of leg and thigh muscle volumes and mean thigh cross-sectional area
      (CSA), and a test of agility. The agility T-half test showed a significant
      interaction effect (p=0.001; eta=0.422), with an inter-group difference in effect
      size (d) of 1.27 (dTG=1.24 vs. dCG=-0.03). The SJ displayed no interaction
      effect. The interaction effects for half back-squat (d=2.73, eta=0.740) and CMJ
      (d=3.76, eta=0.700) were large, but that for RT was smaller (eta=0.460) than that
      for JT (eta=0.745). The throwing velocity of C decreased for both measures, with
      negative effect sizes (d=-0.18 and d=-0.93 respectively). Upper body, leg, and
      thigh muscle volumes and thigh CSA increased significantly after resistance
      training. However, repeated-sprint parameters showed no significant changes.
      During the competitive season, 10 weeks of RCT with only 2 training sessions per
      week improved numerous measures of athletic performance in handball players, and
      such conditioning can be highly recommended as part of the annual training
      program for elite handball players.

PMID- 29016477
TI  - Shod vs. Barefoot Effects on Force and Power Development During a Conventional
      Deadlift.
AB  - Hammer, ME, Meir, RA, Whitting, JW, and Crowley-McHattan, ZJ. Shod vs. barefoot
      effects on force and power development during a conventional deadlift. J Strength
      Cond Res 32(6): 1525-1530, 2018-The kinetics of a conventional deadlift in shod
      (S) vs. unshod (US) footwear conditions in 10 male participants (mean +/- SD, age
      = 27.0 +/- 5.8 years; body mass = 78.7 +/- 11.5 kg; height = 175.8 +/- 8.2 cm; 1
      repetition maximum [1RM] deadlift = 155.8 +/- 25.8 kg) was assessed in 2 testing
      sessions. A counterbalanced, cross-over experimental design was used with
      different loads (60 and 80% 1RM). Four sets of 4 repetitions were prescribed per
      session with 2 sets per shoe and with each shoe condition involving 1 set per
      load. Peak vertical force (PF), rate of force development (RFD), time to peak
      force (TPF), anterior-posterior (COP-AP) and mediolateral (COP-ML) center of
      pressure excursion, and barbell peak power data were recorded during all
      repetitions. Except for RFD (F = 6.389; p = 0.045; etap = 0.516) and ML-COP (F =
      6.696; p = 0.041; etap = 0.527), there were no other significant main effects of
      shoe. There were significant main effects of load for PF (p <= 0.05), COP-AP (p =
      0.011), TPF (p = 0.018), and COP-AP (p = 0.011). There were no significant
      interactions found between session, shoe, and load (p range from 0.944 to 0.086).
      Although the US condition may have produced changes in RFD and ML-COP compared
      with the shod condition, there is only limited evidence in the current study to
      support this lifting technique for the conventional deadlift. Further
      investigation is required to clarify any possible implications of this result and
      its benefit to lifters.

PMID- 29016478
TI  - Subjective And Objective Responses To Two Rugby 7's World Series Competitions.
AB  - The purpose was to examine the utility of subjective and objective measures of
      player preparedness, interpreted at both a group and individual level, during two
      consecutive competitions of the World Rugby Sevens Series (WRSS). Subjective
      (sleep, energy and muscle soreness ratings) and objective [heart rate (HR) at
      rest (HRREST) and in response to submaximal exercise (HREX)] measures were
      obtained from 16 male Rugby-7s players from one team for three consecutive days
      (D1-3) at home (HOME) and upon arrival at four tournament (T1-4) locations (T1
      New Zealand and T2-USA; T3-Hong Kong and T4-Tokyo) across two WRSS competitions
      (two tournaments per competition) separated by 1 month. At a group level, energy
      ratings were significantly lower in T2 and T4 compared to HOME, and on D1 T2
      compared to D1 T1 (p=<0.05). Greatest variability in subjective ratings was
      observed during T1 and T3 at an individual level, particularly for sleep quality.
      Though at a group level HRREST and HREX significantly decreased in T1-4 compared
      to HOME (p=<0.05), there was only a ~50% agreement between the direction of
      change in HR indices at an individual level. Results from the present study
      suggest that relocation between tournaments within WRSS competitions disrupts
      player preparedness measures to the largest degree. Hence, this time period could
      be targeted by practitioners with appropriate recovery and/or sleep promoting
      interventions and/or modulation of match-/training-load. Moreover, subjective
      rather than objective measures appear of greater use to inform player
      preparedness decision making, particularly at an individual compared to a group
      level.

PMID- 29016479
TI  - The Effects of Foam Rolling as a Recovery Tool in Professional Soccer Players.
AB  - Foam rolling (FR) is a common strategy used after training and competition by
      players. However, no previous studies have assessed the effectiveness of FR as
      recovery tool in sports populations. The aim of this study was to examine the
      effectiveness of FR (20 minutes of foam rolling exercises on quadriceps,
      hamstrings, adductors, gluteals, and gastrocnemius) and passive recovery (20
      minutes sit on a bench) interventions performed immediately after a training
      session on Total Quality Recovery (TQR), perceived muscle soreness, jump
      performance, agility, sprint, and flexibility 24 hours after the training. During
      2 experimental sessions, 18 professional soccer players (age 26.6 +/- 3.3 years;
      height: 180.2 +/- 4.5 cm; body mass: 75.8 +/- 4.7 kg) participated in a
      randomized fully controlled trial design. The first session was designed to
      collect the pre-test values of each variable. After baseline measurements, the
      players performed a standardized soccer training. At the end of training unit,
      all the players were randomly assigned to the FR recovery group and the passive
      recovery group. A second experimental session was carried out to obtain the
      posttest values. Results from the between-group analyses showed that FR had a
      large effect on the recovery in agility (Effect Sizes [ES]= 1.06), TQR (ES=
      1.08), and perceived muscle soreness (ES= 1.02) in comparison to passive recovery
      group at 24 h post-training. Thus, it is recommended soccer coaches and physical
      trainers working with high-level players use a structured recovery session
      lasting from 15 to 20 min based on FR exercises that could be implemented at the
      end of a training session to enhance recovery between training loads.

PMID- 29016480
TI  - Revisiting the Single-Visit Protocol for Determining the Electromyographic
      Fatigue Threshold.
AB  - Khan, FL, Lawal, JM, Kapture, DO, Swingle, JD, and Malek, MH. Revisiting the
      single-visit protocol for determining the electromyographic fatigue threshold. J
      Strength Cond Res 31(12): 3503-3507, 2017-The electromyographic fatigue threshold
      (EMGFT) has been shown to demarcate between nonfatiguing and fatiguing exercise
      workloads. One potential limitation of incorporating the single EMGFT test in a
      clinical setting is the 2-minute stage increment inherit to the protocol. In most
      rehabilitation clinics, time with the client is limited, and any testing
      procedure needs to consider this factor. The purpose of this study, therefore,
      was to determine whether or not the estimation of the EMGFT is influenced by
      reducing the incremental stage to 1-minute intervals. We hypothesized that the 1
      minute incremental protocol would provide similar estimates of the EMGFT as the
      traditional 2-minute incremental protocol. Nine college-aged men performed the
      single-leg knee-extensor ergometry at 1-minute (3 W) and 2-minute (6 W) stages in
      random order separated by 7 days. The exercise indices and the EMGFT were
      determined from the 2 protocols and analyzed using a paired samples t test. The
      EMG amplitude was assessed from the rectus femoris muscle. The results indicated
      significant differences between protocols for maximal power output (1 minute:
      31.7 +/- 2.2 W vs. 2 minutes: 38.0 +/- 3.3 W, p = 0.016) and heart rate at end
      exercise (1 minute: 137 +/- 5 b.min vs. 2 minutes: 148 +/- 5 b.min, p = 0.024).
      There were, however, no significant mean differences for the EMGFT (1 minute:
      19.8 +/- 1.8 vs. 2 minutes: 20.3 +/- 1.9 W, p = 0.63) and rating of perceived
      exertion (RPE) for the exercised leg (1 minute: 9 +/- 0 vs. 2 minutes: 9 +/- 1, p
      = 0.68). These results indicate that reducing the exercise protocol by 50% did
      not change the estimated EMGFT. The practical application of this finding resides
      in the potential use in sports or rehabilitative settings in which there is
      limited time with the client and no objective measures to determine neuromuscular
      fatigue for aerobic exercise.

PMID- 29016481
TI  - Auto-regulated exercise selection training regimen produces small increases in
      lean body mass and maximal strength adaptations in strength-trained individuals.
AB  - The purpose of this investigation was to compare the effects of auto-regulatory
      exercise selection (AES) vs. fixed exercise selection (FES) on muscular
      adaptations in strength-trained individuals. Seventeen males (Mean +/- SD; age =
      24 +/- 5.45 years; height = 180.3 +/- 7.54cm, lean body mass [LBM] 66.44 +/-
      6.59kg; squat and bench press 1RM: body mass ratio 1.87, 1.38 respectively) were
      randomly assigned into either AES or FES. Both groups trained three times a week
      for 9 weeks. AES self-selected the exercises for each session, whereas FES was
      required to perform exercises in a fixed order. LBM was assessed via DEXA and
      maximum strength via 1RM testing, pre and post training intervention. Total
      volume load was significantly higher for AES than for FES (AES: 573,288kg +/-
      67,505, FES: 464,600 +/- 95,595, p=0.0240). For LBM, there was a significant main
      time effect (p=0.009). However, confidence interval analysis (95%CIdiff)
      suggested that only AES significantly increased LBM (AES: 2.47%, ES: 0.35, 95%
      CIdiff [0.030kg: 3.197kg], FES: 1.37 %, ES: 0.21, 95% CIdiff [-0.500kg:
      2.475kg]). There was a significant main time effect for maximum strength
      (p<=0.0001). However, 95% CIdiff suggested that only AES significantly improved
      Bench-press 1RM (AES: 6.48%, ES: 0.50, 95% CIdiff [0.312kg: 11.42kg; FES: 5.14%,
      ES: 0.43 95%CIdiff [-0.311kg: 11.42kg]. On the other hand for back squat 1RM
      similar responses were observed between groups, (AES: 9.55%, ES: 0.76 95% CIdiff
      [0.04kg: 28.37kg], FES: 11.54%, ES: 0.80, 95%CIdiff [1.8kg: 28.5kg]. Our
      findings, suggest AES may provide a small advantage in LBM and upper body maximal
      strength in strength-trained individuals.

PMID- 29016482
TI  - Relationship between physical performance testing results and peak running
      intensity during professional rugby league match play.
AB  - The purpose of this study was to examine the relationship between individual
      athletes' physical characteristics and both the peak running intensities and the
      decline in peak running intensities during competition. Twenty-two professional
      rugby league athletes (age; 24.1 +/- 4.0 years, body mass; 101.4 +/- 9.5 kg)
      underwent a series of physical testing procedures. Peak running intensity was
      determined using a moving average technique, applied to the speed (m.min),
      acceleration/deceleration (m.s) and metabolic power (W.kg) during competition,
      across 10 different durations. The power law relationship was then established,
      yielding an intercept and slope for the movement variables. Mixed linear models
      were then used to determine the relationship between physical characteristics and
      intercept and slope values. There were large, positive relationships between a
      player's maximal speed and both peak running speeds (ES = 0.56, 90% CI: 0.20 to
      0.78) and metabolic power (0.57, 0.21 to 0.79) during competition. In contrast,
      there were large, negative associations between maximal speed and the rate of
      decline in running speed (-0.60, -0.81 to -0.27) and metabolic power (-0.65, 
      0.83 to -0.32) during competition. Similarly, there were negative associations
      between relative squat strength and the rate of decline in running speed
      (moderate: -0.41, -0.69 to -0.04) and metabolic power (large: -0.53, -0.77 to 
      0.17) during competition. The findings of this study demonstrate that a players
      running intensity during competition is underpinned by the individual athletes
      physiological qualities. Athletes demonstrating higher maximal speeds in testing
      were able to maintain higher running intensities over short durations, but had a
      greater decrease in running intensity as duration increased.

PMID- 29016483
TI  - Hydration Status and Thermoregulatory Responses in Drivers During Competitive
      Racing.
AB  - Carlson, LA, Lawrence, MA, and Kenefick, RW. Hydration status and
      thermoregulatory responses in drivers during competitive racing. J Strength Cond
      Res 32(7): 2061-2065, 2018-Stock car drivers are exposed to high ambient
      temperatures, further complicated by the fact that they are encapsulated in
      protective clothing; however, the hydration status of these drivers has not been
      determined. This study quantified the degree of fluid losses during a competitive
      event in hot conditions. Nine male stock car drivers (29.6 +/- 9.4 years, 177.8
      +/- 3.0 cm, 81.5 +/- 18.5 kg) were studied during a Pro Series Division NASCAR
      race. Sweat rate (SR) and dehydration was determined through nude body weights
      (BWs). Prerace BW was 81.5 +/- 18.5 kg and decreased to 81.1 +/- 18.5 kg after
      race (p = 0.001). Body weight loss after race was 0.77 +/- 0.3% and mean SR was
      0.63 +/- 0.4 L.h. Intestinal core temperature increased from 38.0 +/- 0.4 to 38.5
      +/- 0.4 degrees  C after race (p = 0.001). Skin temperature increased from 35.8
      +/- 0.8 to 36.9 +/- 0.8 degrees  C after race (p = 0.001), whereas the core-to
      skin temperature gradient narrowed from 2.2 +/- 0.9 to 1.6 +/- 0.9 degrees  C,
      before race to after race (p = 0.001). Heart rates after race were 89 +/- 0.0% of
      the drivers' age-predicted maximum heart rate (HR). Fluid losses during
      competitive racing can be significant. Without a fluid replacement strategy,
      fluid losses may exceed 3% of BW and could negatively impact driving performance
      in longer races.

PMID- 29016484
TI  - A Novel Combination of Biomarkers to Herald the Onset of Sepsis Prior to the
      Manifestation of Symptoms.
AB  - Sepsis, which kills over 200,000 patients and costs over $20 billion in the
      United States alone, presents a constant but preventable challenge in the
      healthcare system. Among the more challenging problems that it presents is
      misdiagnosis due to conflation with other inflammatory processes, as its
      mechanisms are identical to those of other inflammatory states. Unfortunately,
      current biomarker tests can only assess the severity and mortality risk of each
      case, whereas no single test exists that can predict sepsis prior to the onset of
      symptoms for the purpose of pre-emptive care and monitoring. We propose that a
      single test utilizing three, rather than two, biomarkers that appear most quickly
      in the blood and are the most specific for sepsis rather than trauma, may improve
      diagnostic accuracy and lead to lessened patient morbidity and mortality. Such a
      test would vastly improve patient outcomes and quality of life, prevent
      complications for sepsis survivors, and prevent hospital readmissions, saving the
      American healthcare system money. This review summarizes the current use of
      sepsis biomarkers to prognosticate morbidity and mortality, and rejects the
      current single-biomarker and even combination biomarker tests as non-specific and
      inaccurate for current patient needs/pro-inflammatory cytokines, general markers
      of inflammation, and proteins specific to myeloid cells (and therefore to
      infection) are discussed. Ultimately, the review suggests a three-biomarker test
      of procalcitonin (PCT), interleukin-6 (IL-6), and soluble triggering receptor
      expressed on myeloid cells-1 (sTREM-1) to diagnose sepsis before the onset of
      symptoms.

PMID- 29016485
TI  - A Medically Supervised Pregnancy Exercise Intervention in Obese Women: A
      Randomized Controlled Trial.
AB  - OBJECTIVE: To evaluate whether an intensive, medically supervised exercise
      intervention improved maternal glycemia and gestational weight gain in obese
      pregnant women when compared with routine prenatal care. METHODS: This randomized
      controlled trial compared a medically supervised exercise intervention with
      routine prenatal care. The primary outcome was a reduction in mean maternal
      fasting plasma glucose in the intervention group by 6.9 mg/dL at the time of a 75
      g oral glucose tolerance test at 24-28 weeks of gestation. Secondary outcomes
      included excessive gestational weight gain. The intervention consisted of 50-60
      minutes of exercise: warm-up, resistance or weights, aerobic exercises, and cool
      down. All women received routine prenatal care. Power calculation determined that
      24 women were required per group to detect a difference of 6.9 mg/dL in fasting
      plasma glucose between groups based on an independent-sample t test for
      statistical power of 80% at a type I error rate of 0.05. A sample size of 44 per
      group was planned to allow a dropout rate of 33%. RESULTS: From November 2013
      through August 2015, 88 women were randomized: 44 each to the exercise and
      control groups. Eight women in the control group and 11 in the intervention group
      did not complete the trial at 6 weeks postpartum (P=.61), but 43 in each group
      attended the 24- to 28-week glucose screen. There were no baseline maternal
      differences between groups. Classes commenced at a mean of 13 4/7+/-1 2/7 weeks
      of gestation. In early pregnancy, 51.1% (n=45/88) had an elevated fasting plasma
      glucose (92-125 mg/dL). There was no difference in the mean fasting plasma
      glucose at 24-28 weeks of gestation: 90.0+/-9.0 mg/dL (n=43) compared with 93.6+/
      7.2 mg/dL (n=43) (P=.13) or in the incidence of gestational diabetes mellitus at
      24-28 weeks of gestation: 48.8% (n=21/43) compared with 58.1% (n=25/43) (P=.51)
      in the control and exercise groups, respectively. At 36 weeks of gestation,
      excessive gestational weight gain greater than 9.1 kg was lower in the exercise
      group, 23.5% compared with 45.2% in the control group (P<.05). CONCLUSION: An
      intensive, medically supervised exercise intervention for obese women from early
      pregnancy did not improve maternal glycemia. Pregnant women who are obese,
      however, should be advised to exercise because it attenuates excessive
      gestational weight gain. CLINICAL TRIAL REGISTRATION: International Standard
      Randomised Controlled Trials (ISRCTN) registry, ISRCTN 31045925.

PMID- 29016486
TI  - Salpingectomy for Sterilization: Change in Practice in a Large Integrated Health
      Care System, 2011-2016.
AB  - OBJECTIVE: To evaluate the utilization rate of salpingectomy for cesarean
      deliveries and postpartum and interval tubal sterilization procedures. METHODS:
      This is a retrospective cohort study using the electronic medical record to
      identify women older than 18 years of age undergoing surgical sterilization from
      June 2011 to May 2016 in an integrated health care system. The primary objective
      is to describe the change in utilization rate of salpingectomy for tubal
      sterilization procedures over time and after a systemwide practice recommendation
      was issued in 2013. Rates of salpingectomy and tubal occlusion were calculated
      for each of the five 1-year intervals in the study. Secondary outcomes included
      blood loss, operating time, length of stay, readmission, and emergency department
      visits. RESULTS: A total of 10,741 tubal sterilization procedures were
      identified. There was an increase in salpingectomies from 0.4% (8/1,938; 95% CI
      0.2-0.8) to 35.5% (902/2,538; 95% CI 33.7-37.4) of tubal sterilization procedures
      performed over the study period (test for trend, P<.001). Salpingectomy instead
      of tubal occlusion increased at cesarean delivery from 0.1% (1/1,141; 95% CI 0.0
      0.5) to 9.2% (125/1,354; 95% CI 7.8-10.9) (test for trend, P<.001); postpartum
      from 0% (0/124; 95% CI 0.0-3.0) to 4.5% (9/201; 95% CI 2.4-8.3) (test for trend,
      P=.003); and as an interval (nonpartum) tubal sterilization procedure from 1%
      (7/673; 95% CI 0.5-2.1) to 78% (768/983; 95% CI 75.4-80.6) (test for trend,
      P<.001). Median operative minutes was increased from 52 (95% CI 51-52) to 61.5
      (95% CI 57-64), from 33 (95% CI 32-34) to 50 (95% CI 35-64), and from 30 (95% CI
      29-30) to 33 (95% CI 32-33), respectively, for salpingectomy compared with tubal
      occlusion at cesarean delivery and postpartum and interval sterilization. Median
      blood loss was similar for salpingectomy and tubal occlusion at cesarean delivery
      (660 mL; 95% CI 600-700 mL compared with 700 mL; 95% CI 680-700 mL) and interval
      sterilization (both 5 mL; 95% CI 5-5 mL) but was more for salpingectomy
      postpartum (250 mL; 95% CI 200-500 mL compared with 200 mL; 95% CI 200-200 mL).
      CONCLUSION: There was a significant increase in salpingectomy for sterilization
      from June 2011 to May 2016. In the final year of the study, salpingectomy
      accounted for 78% of interval laparoscopic tubal sterilization procedures and 9%
      of intrapartum and postpartum procedures.

PMID- 29016487
TI  - Ovarian Vein Thrombosis: Incidence of Recurrent Venous Thromboembolism and
      Survival.
AB  - OBJECTIVE: To identify the risk of venous thromboembolism recurrence, major
      bleeding, and mortality in patients with ovarian vein thrombosis so as to better
      define optimal treatment strategies. METHODS: Patients with ovarian vein
      thrombosis (1990-2015) and age- and gender-matched patients with contemporary leg
      deep vein thrombosis (DVT) were assessed for differences in etiology, venous
      thromboembolism recurrence, and survival in a case-control study. RESULTS: Over
      the timeframe of this study, only 219 ovarian vein thrombosis cases were
      identified compared with 13,417 leg DVTs. Median duration of follow-up was 1.23
      years (interquartile range 0.25-4.14). Pulmonary embolism was identified at
      presentation in 6% of patients with ovarian vein thrombosis and 16% of those with
      DVT (P=.001). Frequent causes of ovarian vein thrombosis included cancer,
      hormonal stimulation, surgery, and hospitalization. Cancer was twofold more
      frequent in patients with ovarian vein thrombosis (44% compared with 21%; P<.01).
      Despite being less frequently treated with anticoagulation (ovarian vein
      thrombosis 54% compared with DVT 98%, P<.001), venous thromboembolism recurrence
      rates were similar between groups (ovarian vein thrombosis 2.3 compared with DVT
      1.8 per 100 patient-years, P=.49). A personal history of venous thromboembolism
      and preceding surgery was found to be an independent risk factor for venous
      thromboembolism recurrence among those treated with anticoagulation (hazard ratio
      6.7, P=.04 and hazard ratio 13.6, P=.03, respectively). There was no significant
      difference in overall survival. CONCLUSION: Ovarian vein thrombosis is a rare
      thrombotic condition with an incidence 60-fold lower compared with leg DVT in our
      institution. The striking association with cancer adversely affects overall
      survival rates in patients with ovarian vein thrombosis. Venous thromboembolism
      recurrence rates argue for anticoagulation with a direct oral anticoagulant or
      vitamin K antagonist, particularly in those with a history of venous
      thromboembolism.

PMID- 29016488
TI  - Pregnancy Outcomes Among Deaf Women in Washington State, 1987-2012.
AB  - OBJECTIVE: To evaluate pregnancy and neonatal outcomes among deaf women using
      population-based vital records data in Washington State from 1987 to 2012.
      METHODS: We performed a retrospective cohort study using the Washington State
      birth and fetal death records linked to state hospital discharge records to
      identify women with diagnosis codes for deafness indicated at their delivery
      hospitalization and compared them with randomly selected women without these
      codes. Pregnancy conditions and outcomes evaluated included gestational diabetes,
      preeclampsia, placental abruption, labor induction, and cesarean delivery.
      Neonatal outcomes evaluated included preterm gestational age (less than 28, 28 to
      less than 37 weeks) at delivery and low birth weight. We also assessed length of
      maternal and neonatal delivery hospitalization. We performed Poisson regression
      to estimate relative risks (RRs) and 95% CIs for each outcome, adjusting for
      birth year, maternal age, and parity. RESULTS: Most adverse pregnancy and
      neonatal outcomes were similar for deaf and comparison women. Among women who
      underwent vaginal delivery, deaf women were more than twofold (RR 2.15, 95% CI
      1.43-3.22) more likely to have a delivery hospitalization of 4 or more days (6.0%
      compared with 2.8%). We found a modestly increased risk of cesarean delivery (RR
      1.15, 95% CI 1.01-1.30), with 29.9% of deaf compared with 25.6% of nondeaf women
      having a cesarean delivery. CONCLUSION: Deaf women are not at increased risk of
      the majority of adverse pregnancy and neonatal outcomes. Obstetric care providers
      may use our findings in counseling this special population of prenatal patients.

PMID- 29016489
TI  - First-Trimester Serum Fatty Acid-Binding Protein 4 and Subsequent Gestational
      Diabetes Mellitus.
AB  - OBJECTIVE: To examine whether plasma fatty acid-binding protein 4 concentrations,
      measured in the first trimester, are associated with gestational diabetes
      mellitus (GDM). METHODS: This prospective, multicenter cohort study was conducted
      at three maternity centers in two cities (Harbin and Beijing) in China from July
      2015 to June 2016. Data for fasting plasma glucose and fatty acid-binding protein
      4 concentrations in the first trimester and one-step GDM screening with a 75-g
      oral glucose tolerance test performed between 24 and 28 weeks of gestation were
      collected and analyzed. RESULTS: Plasma from women in the first trimester was
      available for 1,150 women, of whom 135 (11.7%) developed GDM. The GDM
      distribution across the fatty acid-binding protein 4 quartiles ranged from 3.8%
      (first quartile) to 21.6% (fourth quartile). In multivariate models comparing the
      second (quartile 2), third, and fourth quartiles against the first quartile of
      fatty acid-binding protein 4, concentrations of fatty acid-binding protein 4 in
      quartile 2, quartile 3, and quartile 4 were associated with the development of
      GDM with respective associated adjusted odds ratios (95% CIs) of 1.76 (1.21
      2.58), 2.36 (1.55-4.29), and 3.57 (1.99-6.11). A significant difference in the
      area under receiver operating characteristic curve between established risk
      factors alone and the addition of fatty acid-binding protein 4 concentrations was
      observed (difference 0.042 [95% CI 0.028-0.055]; P=.03). CONCLUSIONS: Higher
      fatty acid-binding protein 4 concentrations in the first trimester visit were
      associated with increased risk of GDM and might be useful in identifying women at
      risk for GDM for early prevention strategies.

PMID- 29016490
TI  - Neonatal Morbidity and Maternal Complication Rates in Women With a Delivery Body
      Mass Index of 60 or Higher.
AB  - OBJECTIVE: To investigate neonatal morbidity and maternal complication rates with
      delivery body mass index (BMI) 60 or greater. METHODS: This retrospective,
      multicenter cohort study included singleton pregnancies between 23 and 42 weeks
      of gestation from January 2005 to April 2016. Women with BMI 60 or greater were
      compared with a random sample of women with BMI 30-59. The primary outcome,
      composite neonatal morbidity, was defined as 5-minute Apgar score less than 7,
      hypoglycemia, respiratory distress syndrome, sepsis, hospital stay greater than 5
      days, neonatal intensive care unit admission, or neonatal death. Secondary
      outcomes included maternal labor and delivery characteristics and complication
      rates. Kruskal-Wallis tests and chi or Fisher exact tests were used to compare
      BMI categories. Multivariable logistic regression was used for adjusted analysis.
      RESULTS: The study included 338 women, with 39 in the BMI 60 or greater group. An
      association between obesity and neonatal morbidity was found. Increasing BMI
      correlated with increasing neonatal morbidity, with the highest rates among those
      with BMI 60 or greater (BMI 30-39 [17%], 40-49 [19%], 50-59 [22%], 60 or greater
      [56%]; P<.001). After adjustment for confounders, obese women with BMI less than
      60 had at least a 75% reduction in odds of neonatal morbidity compared with women
      with BMI 60 or greater (BMI 30-39 adjusted odds ratio [OR] 0.22 [0.1-0.5], 40-49
      adjusted OR 0.23 [0.1-0.6], 50-59 adjusted OR 0.25 [0.1-0.6]). Maternal
      complication rates including labor induction, cesarean delivery, wound
      complication, postpartum hemorrhage, and hospital stay greater than 5 days were
      also significantly increased with BMI 60 or greater. CONCLUSION: A BMI 60 or
      greater at the time of delivery is significantly associated with increased
      neonatal morbidity and increased maternal complication rates. In addition,
      neonatal morbidity and maternal complication rates with BMI 60 or greater were
      significantly higher when compared with women in any lesser obese BMI cohort
      between 30 and 59.

PMID- 29016492
TI  - Characterizing the Functional Decline of Older Women With Incident Urinary
      Incontinence.
AB  - OBJECTIVE: To characterize change in physical performance and differential
      prevalence of low skeletal muscle mass and strength (sarcopenia) and lower 25
      hydroxyvitamin D concentrations among older women who developed urinary
      incontinence (UI) symptoms. METHODS: This is a secondary analysis of the Health,
      Aging, and Body Composition Study. Urinary incontinence symptoms were assessed
      using validated questions. The Short Physical Performance Battery measured
      physical performance. Sarcopenia, defined by low muscle mass and strength, was
      determined using validated cutoffs for gait speed, grip strength, and
      appendicular skeletal muscle mass. All parameters were evaluated at baseline and
      year 4. Serum 25-hydroxyvitamin D concentrations were assessed at year 2. The
      primary outcome was change in Short Physical Performance Battery total scores.
      Sarcopenia and lower serum 25-hydroxyvitamin D concentrations have been
      independently associated with poor physical performance and UI and were therefore
      included as secondary outcomes. Univariate and multivariate analyses were used to
      characterize the associations of change in physical performance from baseline to
      year 4, incidence of sarcopenia, and lower serum 25-hydroxyvitamin D on the
      development of UI symptoms. RESULTS: Of the 1,583 women enrolled, 910 were
      excluded (730 had baseline UI; 180 with missing data). Six hundred seventy-three
      women were continent at baseline; 223 (33%) developed UI symptoms at year 4. SPPB
      total scores significantly declined in women with UI versus continent women (mean
      difference continent-incident UI 0.32, 95% CI 0.04-0.60, P=.02). Of subscale
      measures, standing balance showed the greatest decline at 0.20 (0.05-0.36;
      continent-incident UI, respectively; P=.009). Sarcopenia developed at a higher
      rate with incident UI (adjusted odds ratio [OR] 1.7, 95% CI 1.0-2.9). Low 25
      hydroxyvitamin D was not associated with incident UI (adjusted OR 1.1, 95% CI 0.7
      1.6 and 1.1, 95% CI 0.7-1.6 for deficient or insufficient versus sufficient
      status, respectively). CONCLUSION: We observed a significant decline in standing
      balance among older women who developed UI symptoms. This decline may be
      associated with coinciding development of sarcopenia.

PMID- 29016491
TI  - Expanding Prenatal Care to Unauthorized Immigrant Women and the Effects on Infant
      Health.
AB  - OBJECTIVE: To measure the effect of access to prenatal care on unauthorized and
      low-income, new legal permanent resident immigrant women and their offspring.
      METHODS: We used a difference-in-differences design that leverages the staggered
      rollout of Emergency Medicaid Plus by county from 2008 to 2013 as a natural
      experiment to estimate the effect on health service utilization for women and
      health outcomes for their infants. Regular Medicaid pregnancies were used as an
      additional control in a triple difference design. RESULTS: Our sample included
      pregnancies covered by Emergency Medicaid (35,182), Emergency Medicaid Plus
      (12,510), and Medicaid (166,054). After expansion of access to prenatal care,
      there was an increase in prenatal visits (7.2 more visits, 95% CI 6.45-7.96),
      receipt of adequate prenatal care (28% increased rate, CI 26-31), rates of
      diabetes screening (61% increased rate, CI 56-66), and fetal ultrasonograms (74%
      increased rate, CI 72-76). Maternal access to prenatal care was also associated
      with an increased number of well child visits (0.24 more visits, CI 0.07-0.41),
      increased rates of recommended screenings and vaccines (0.04 increased
      probability, CI 0.002-0.074), and reduced infant mortality (-1.01/1,000, CI -1.42
      to -0.60) and rates of extremely low birth weight (less than 1,000 g) (
      1.33/1,000, CI -2.44 to -0.21). CONCLUSION: Our results provide evidence of
      increased utilization and improved health outcomes for unauthorized immigrants
      and their children who are U.S. citizens after introduction of prenatal care
      expansion in Oregon. This study contributes to the debate around reauthorization
      of the Children's Health Insurance Program in 2017.

PMID- 29016494
TI  - Maternal and Neonatal Outcomes in Indicated Preterm Births Based on the Intended
      Mode of Delivery.
AB  - OBJECTIVE: To compare maternal and neonatal outcomes in women who underwent
      induction of labor or planned cesarean delivery in indicated preterm births
      before 34 weeks of gestation. METHODS: We conducted a retrospective cohort study
      of all indicated singleton preterm births (23-34 weeks of gestation) in a
      tertiary center from 2011 to 2014. The primary maternal outcome was a composite
      of early postpartum hemorrhage, blood transfusion, operative complications,
      postpartum complications, and clinical chorioamnionitis. The primary neonatal
      outcome was a composite of neonatal death, cardiopulmonary resuscitation in the
      delivery room, grade 3 or 4 intraventricular hemorrhage, necrotizing
      enterocolitis, culture-proven sepsis, birth trauma, arterial cord gas pH less
      than 7 or base excess less than -12, and 5-minute Apgar score 3 or less. Outcomes
      were compared by intended mode of delivery (induction of labor compared with
      cesarean) and adjusted for confounders. In secondary analyses, maternal and
      neonatal outcomes based on the intended mode of delivery were stratified by
      gestational age (23-27 6/7, 28-31 6/7, and 32-33 6/7 weeks of gestation).
      RESULTS: Of 629 patients with indicated early preterm births during the study
      period, 331 (53%) underwent induction of labor, of whom 208 (63%) delivered
      vaginally. Induction of labor was not associated with an increased risk of the
      primary maternal (16.3% compared with 19.5%, adjusted odds ratio [OR] 0.8, 95% CI
      0.5-1.3) or neonatal composite outcome (14.5% compared with 35.9%, adjusted OR
      0.7, 95% CI 0.4-1.1). Analyses stratified by gestational age were consistent with
      the overall analysis. CONCLUSION: Maternal and neonatal outcomes do not differ
      based on the intended mode of delivery. Induction of labor should be considered
      when early preterm birth is indicated.

PMID- 29016493
TI  - Early Pregnancy Diabetes Screening and Diagnosis: Prevalence, Rates of Abnormal
      Test Results, and Associated Factors.
AB  - OBJECTIVE: To evaluate the prevalence of early diabetes screening in pregnancy,
      rates of abnormal diabetes test results before 24 weeks of gestation, and factors
      associated with early diabetes screening. METHODS: This was a retrospective
      cohort study of all singleton deliveries from 2012 to 2014 among diverse clinical
      practices at a large academic medical center. We assessed rates of early (less
      than 24 weeks of gestation) and routine (at or beyond 24 weeks of gestation)
      diabetes screening, with abnormal test results defined using the Carpenter
      Coustan criteria, a 50-g glucose challenge test result greater than 200 mg/dL, or
      a hemoglobin A1C level greater than 6.5%. Univariate and multivariate analyses
      were used to evaluate clinical and demographic determinants of screening and
      diagnosis. RESULTS: Overall, 1,420 of 11,331 (12.5%) women underwent early
      screening. Increasing body mass index (BMI) category, race, public insurance,
      history of gestational diabetes mellitus, a family history of diabetes, and
      chronic hypertension were associated with early screening. Early screening rates
      rose with increasing BMI category, but only 268 of 551 (48.6%) of women with
      class III obesity underwent early screening. Among those screened early, 2.0% of
      normal-weight women, 4.0% of overweight women, 4.2% of class I obese women, 3.8%
      of class II obese women, and 9.0% of class III obese women had abnormal early
      test results (P<.001). CONCLUSION: Early diabetes screening is used
      inconsistently, and many women with risk factors do not undergo early screening.
      A significant proportion of women with class III obesity will test positive for
      gestational diabetes mellitus before 24 weeks of gestation, and studies are
      urgently needed to assess the effect of early diabetes screening and diagnosis on
      perinatal outcomes in high-risk women.

PMID- 29016495
TI  - A Gartner Duct Cyst Masquerading as Anterior Vaginal Prolapse.
AB  - BACKGROUND: Gartner duct cysts are embryologic remnants of the mesonephric ducts
      that may present as a vaginal mass or cyst. CASE: A patient was referred for
      surgical management of prolapse whose bulging anterior vagina was actually a
      Gartner duct cyst that required excision as a result of symptoms. Preoperative
      magnetic resonance imaging helped confirm the diagnosis. CONCLUSION: A Gartner
      duct cyst may present as a vaginal cyst that, if large, may mimic pelvic organ
      prolapse. The diagnosis should be considered when a patient's individual prolapse
      compartments are inconsistent or when physical examination is suggestive of
      another process.

PMID- 29016496
TI  - Leiomyomas in Pregnancy and Spontaneous Abortion: A Systematic Review and Meta
      analysis.
AB  - OBJECTIVE: To systematically review studies reporting the risk of spontaneous
      abortion among pregnant women of typical reproductive potential with and without
      uterine leiomyomas. DATA SOURCES: We searched PubMed, EMBASE, Web of Science, and
      ClinicalTrials.gov for publications from January 1970 to December 2016. METHODS
      OF STUDY SELECTION: We excluded studies that did not use imaging to uniformly
      document leiomyoma status of all participants, did not have a comparison group
      without leiomyomas, or primarily included women seeking care for recurrent
      miscarriage, infertility care, or assisted reproductive technologies. TABULATION,
      INTEGRATION, AND RESULTS: Two authors independently reviewed eligibility,
      extracted data, and assigned overall quality ratings based on predetermined
      criteria. Of 1,469 articles identified, nine were eligible. Five enrolled general
      obstetric populations and four included women undergoing amniocentesis. In five
      studies in general obstetric populations that included 21,829 pregnancies (1,394
      women with leiomyomas and 20,435 without), only one adjusted for potential
      confounders. This meta-analysis revealed no increase in risk of spontaneous
      abortion among those with leiomyomas compared with those without (11.5% compared
      with 8.0%; risk ratio 1.16, 95% CI 0.80-1.52). When bias from confounding was
      estimated for nonadjusted studies, the aggregate calculated risk ratio was 0.83
      (95% CI 0.68-0.98). CONCLUSION: Leiomyoma presence was not associated with
      increased risk of spontaneous abortion in an analysis of more than 20,000
      pregnant women. Failure of prior studies to adjust for confounders may have led
      to the common clinical belief that leiomyomas are a risk factor for spontaneous
      abortion.

PMID- 29016497
TI  - Discontinuing Oxytocin Infusion in the Active Phase of Labor: A Systematic Review
      and Meta-analysis.
AB  - OBJECTIVE: To evaluate the benefits and harms of discontinuation of oxytocin
      after the active phase of labor is reached. DATA SOURCES: Electronic databases
      (ie, MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, ScienceDirect, the Cochrane
      Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from
      their inception until April 2017. METHODS OF STUDY SELECTION: We included all
      randomized controlled trials comparing discontinuation (ie, intervention group)
      and continuation (ie, control group) of oxytocin infusion after the active phase
      of labor is reached, either after induction or augmentation of labor.
      Discontinuation of oxytocin infusion was defined as discontinuing oxytocin
      infusion when the active phase of labor was achieved. Continuation of oxytocin
      infusion was defined as continuing oxytocin infusion until delivery. Only trials
      in singleton gestations with vertex presentation at term were included. The
      primary outcome was the incidence of cesarean delivery. TABULATION, INTEGRATION,
      AND RESULTS: Nine randomized controlled trials, including 1,538 singleton
      gestations, were identified as relevant and included in the meta-analysis. All
      nine trials included only women undergoing induction of labor. In the
      discontinuation group, if arrest of labor occurred, usually defined as no
      cervical dilation in 2 hours or inadequate uterine contractions for 2 hours or
      more, oxytocin infusion was restarted. Women in the control group had oxytocin
      continued until delivery usually at the same dose used at the time the active
      phase was reached. Women who were randomized to have discontinuation of oxytocin
      infusion after the active phase of labor was reached had a significantly lower
      risk of cesarean delivery (9.3% compared with 14.7%; relative risk 0.64, 95% CI
      0.48-0.87) and of uterine tachysystole (6.2% compared with 13.1%; relative risk
      0.53, 95% CI 0.33-0.84) compared with those who were randomized to have
      continuation of oxytocin infusion until delivery. Discontinuation of oxytocin
      infusion was associated with an increase in the duration of the active phase of
      labor (mean difference 27.65 minutes, 95% CI 3.94-51.36). CONCLUSION: In
      singleton gestations with cephalic presentation at term undergoing induction,
      discontinuation of oxytocin infusion after the active phase of labor at
      approximately 5 cm is reached reduces the risk of cesarean delivery and of
      uterine tachysystole compared with continuous oxytocin infusion. Given this
      evidence, discontinuation of oxytocin infusion once the active stage of labor is
      established in women being induced should be considered as an alternative
      management plan.

PMID- 29016498
TI  - Clinical Factors Associated With Presentation Change of the Second Twin After
      Vaginal Delivery of the First Twin.
AB  - OBJECTIVE: To identify clinical factors associated with a change from vertex to
      nonvertex presentation in the second twin after vaginal birth of the first.
      METHODS: We assembled a retrospective cohort of women with viable vertex-vertex
      twin pregnancies who delivered the presenting twin vaginally. Women whose second
      twin changed from vertex to nonvertex after vaginal birth of the first were
      classified as experiencing an intrapartum change in presentation. Characteristics
      associated with intrapartum presentation change in a univariate analysis with a P
      value <=.10 were then evaluated in a multivariate logistic regression model.
      RESULTS: Four-hundred fifty women met inclusion criteria, of whom 55 (12%) had
      intrapartum presentation change of the second twin. Women experiencing
      intrapartum presentation change were more likely to be multiparous (69% compared
      with 47%, P<.01) and to have had a change in the presentation of the second twin
      between the most recent antepartum ultrasonogram and the ultrasonogram done on
      admission to labor and delivery (11% compared with 4%, P=.04). In an adjusted
      analysis, multiparity and gestational age less than 34 weeks were significantly
      associated with presentation change (adjusted odds ratio [OR] 2.9, 95% CI 1.5-5.6
      and adjusted OR 2.6, 95% CI 1.1-5.9, respectively). Women with intrapartum
      presentation change were more likely to undergo cesarean delivery for their
      second twin (44% compared with 7%, P<.01) with an adjusted OR of 10.50 (95% CI
      5.20-21.20) compared with those with stable intrapartum presentation. Twenty of
      the 24 (83%) cesarean deliveries performed in the intrapartum presentation change
      group were done for issues related to malpresentation. CONCLUSION: Multiparity
      and gestational age less than 34 weeks are associated with intrapartum
      presentation change of the second twin.

PMID- 29016499
TI  - Epidural Analgesia During the Second Stage of Labor: A Randomized Controlled
      Trial.
AB  - OBJECTIVE: To evaluate whether maintaining a motor-sparing epidural analgesia
      infusion affects the duration of the second stage of labor in nulliparous
      parturients compared with a placebo control. METHODS: We conducted a double
      blind, randomized, placebo-controlled trial involving nulliparous women with term
      cephalic singleton pregnancies who requested epidural analgesia. All women
      received epidural analgesia for the first stage of labor using 0.08% ropivacaine
      with 0.4 micrograms/mL sufentanil with patient-controlled epidural analgesia. At
      the onset of the second stage of labor, women were randomized to receive a
      blinded infusion of the same solution or placebo saline infusion. The primary
      outcome was the duration of the second stage of labor. A sample size of 200 per
      group (400 total) was planned to identify at least a 15% difference in duration.
      RESULTS: Between March 2015 and September 2015, 560 patients were screened and
      400 patients (200 in each group) completed the study. Using an intention-to-treat
      analysis, the duration of the second stage was similar between groups (epidural
      52+/-27 minutes compared with saline 51+/-25 minutes, P=.52). The spontaneous
      vaginal delivery rate was also similar (epidural 193 [96.5%] compared with saline
      198 [99%], P=.17). Pain scores were similar between groups at each measurement
      during the second stage. More women who received placebo reported satisfaction
      scores of 8 or less (epidural 32 [16%] compared with saline 61 [30.5%], P=.001).
      CONCLUSION: Maintaining the infusion of epidural medication had no effect on the
      duration of the second stage of labor compared with a placebo infusion. Maternal
      and neonatal outcomes were similar. A low concentration of epidural local
      anesthetic does not affect the duration of the second stage of labor. CLINICAL
      TRIAL REGISTRATION: Chinese Clinical Trial Register,
      http://www.chictr.org.cn/enindex.aspx, ChiCTR-IOR-15005875.

PMID- 29016500
TI  - Nonreassuring Status: Improving Obstetrician-Gynecologist Wellness.
AB  - Physician wellness directly affects patient and physician health and has broader
      implications for our health systems. A summary of what is known about physician
      wellness in medicine, and obstetrics and gynecology in particular, identifies
      several areas for future focus. To change our culture and the structure of our
      academic health centers in a way that promotes resilience, we suggest greater
      attention to preparedness for practice and attention to work-life integration as
      well as mentoring and professional development.

PMID- 29016501
TI  - What Is New in Cesarean Delivery?: Best Articles From the Past Year.
AB  - This month we focus on current research in cesarean delivery. Dr. Rouse discusses
      six recent publications, which are concluded with a "bottom line" that is a take
      home message. A complete reference for each can be found on on this page along
      with direct links to abstracts.

PMID- 29016502
TI  - Connect the Dots-November 2017.

PMID- 29016503
TI  - Immigration, Pregnancy, and Heath Insurance: New Evidence and Ongoing Debate.

PMID- 29016504
TI  - Accuracy of Four Imaging Techniques for Diagnosis of Posterior Pelvic Floor
      Disorders.
AB  - OBJECTIVE: To establish the diagnostic test accuracy of evacuation proctography,
      magnetic resonance imaging (MRI), transperineal ultrasonography, and endovaginal
      ultrasonography for detecting posterior pelvic floor disorders (rectocele,
      enterocele, intussusception, and anismus) in women with obstructed defecation
      syndrome and secondarily to identify the most patient-friendly imaging technique.
      METHODS: In this prospective cohort study, 131 women with symptoms of obstructed
      defecation syndrome underwent evacuation proctogram, MRI, and transperineal and
      endovaginal ultrasonography. Images were analyzed by two blinded observers. In
      the absence of a reference standard, latent class analysis was used to assess
      diagnostic test accuracy of multiple tests with area under the curve (AUC) as the
      primary outcome measure. Secondary outcome measures were interobserver agreement
      calculated as Cohen's kappa and patient acceptability using a visual analog
      scale. RESULTS: No significant differences in diagnostic accuracy were found
      among the imaging techniques for all the target conditions. Estimates of
      diagnostic test accuracy were highest for rectocele using MRI (AUC 0.79) or
      transperineal ultrasonography (AUC 0.85), for enterocele using transperineal (AUC
      0.73) or endovaginal ultrasonography (AUC 0.87), for intussusception using
      evacuation proctography (AUC 0.76) or endovaginal ultrasonography (AUC 0.77), and
      for anismus using endovaginal (AUC 0.95) or transperineal ultrasonography (AUC
      0.78). Interobserver agreement for the diagnosis of rectocele (kappa 0.53-0.72),
      enterocele (kappa 0.54-0.94) and anismus (kappa 0.43-0.81) was moderate to
      excellent, but poor to fair for intussusception (kappa -0.03 to 0.37) with all
      techniques. Patient acceptability was better for transperineal and endovaginal
      ultrasonography as compared with MRI and evacuation proctography (P<.001).
      CONCLUSION: Evacuation proctography, MRI, and transperineal and endovaginal
      ultrasonography were shown to have similar diagnostic test accuracy. Evacuation
      proctography is not the best available imaging technique. There is no one optimal
      test for the diagnosis of all posterior pelvic floor disorders. Because
      transperineal and endovaginal ultrasonography have good test accuracy and patient
      acceptability, we suggest these could be used for initial assessment of
      obstructed defecation syndrome. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT02239302.

PMID- 29016505
TI  - Implementing a Systematic Approach to Reduce Cesarean Birth Rates in Nulliparous
      Women.
AB  - OBJECTIVE: To implement a systematic approach to safely reduce nulliparous
      cesarean birth rates. METHODS: This is a quality improvement project at two rural
      community hospitals and one urban community hospital in North Carolina. These
      facilities implemented a systematic approach to reduce nulliparous cesarean birth
      rates, aligning with recommendations developed by the Council on Patient Safety
      in Women's Health Care: Patient Safety Bundle on the Safe Reduction of Primary
      Cesarean Births. Health care providers and nurses received education on
      contemporary labor management guidelines developed by the American College of
      Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine
      Obstetric Care Consensus regarding safe prevention of primary cesarean deliveries
      and nurses were instructed on labor support techniques. The preguideline
      implementation period was January 1, 2015, to June 30, 2015. The postguideline
      implementation period was July 1, 2016, to December 31, 2016. The primary outcome
      measured was the nulliparous, term, singleton, vertex cesarean birth rate.
      Secondary outcomes included maternal and neonatal outcomes. Standard statistical
      analysis was used and a P value of <.05 was considered significant. RESULTS:
      There were 434 women identified in the preguideline period and 401 women in the
      postguideline period. The nulliparous, term, singleton, vertex cesarean birth
      rate decreased from 27.9% to 19.7% [odds ratio (OR) 0.63, CI 0.46-0.88]. There
      were improvements in health care provider compliance with following the labor
      management guidelines from 86.2% to 91.5% (OR 1.73, 95% CI 1.11-2.70), the use of
      maternal position changes from 78.7% to 87.5% (OR 1.86, 95% CI 1.29-2.68), and
      use of the peanut birthing ball from 16.8% to 45.2% (OR 3.83, 95% CI 2.84-5.16)
      as provisions for labor support. DISCUSSION: Implementing a systematic approach
      for care of nulliparous women is associated with a decrease in term, singleton,
      vertex cesarean birth rates.

PMID- 29016507
TI  - Cadaveric Nerve and Artery Proximity to Sacrospinous Ligament Fixation Sutures
      Placed by a Suture-Capturing Device.
AB  - OBJECTIVE: To simulate sacrospinous ligament fixation on cadaveric specimens,
      describe the surrounding retroperitoneal anatomy, and estimate the risk to nerves
      and arteries for the purposes of optimizing safe suture placement. METHODS:
      Sacrospinous ligament fixation was performed on eight fresh-tissue female
      cadavers using a Capio ligature capture device. Distances from placed sutures to
      the following structures were measured: ischial spine; fourth sacral root;
      pudendal nerve; the nerve to coccygeus muscle; the nerve to levator ani muscle;
      inferior gluteal artery; and internal pudendal artery. Periligamentous anatomy
      was examined in an additional 17 embalmed cadaver dissections. RESULTS:
      Sacrospinous ligament length was not seen to differ significantly between sides.
      The fourth sacral spinal nerve was seen most commonly associated with the medial
      third of the ligament, whereas the pudendal nerve and the nerves to coccygeus and
      levator ani muscles were associated with the lateral third. The inferior gluteal
      artery was seen leaving the greater sciatic foramen a median 15.8 mm (range 1.8
      48.0, CI 14.9-22.3) above the ligament, whereas the internal pudendal artery
      exited just above the ischial spine. The two sets of sutures were placed 20.5 mm
      (range 9.2-34.4, CI 19.7-24.7) and 24.8 mm (range 12.4-46.2, CI 24.0-30.0) medial
      to the ischial spine, respectively. No structures were directly damaged by placed
      sutures. The nerves to coccygeus and levator ani were closest and arteries
      farthest from the placed sutures. CONCLUSION: The middle segment of the
      sacrospinous ligament has the lowest incidence of nerves and arteries associated
      with it. This study confirms that the nerves supplying the pelvic floor muscles
      are at a higher risk from entrapment than the pudendal nerve.

PMID- 29016506
TI  - Contraception and Conception After Bariatric Surgery.
AB  - OBJECTIVE: To examine contraceptive practices and conception rates after
      bariatric surgery. METHODS: The Longitudinal Assessment of Bariatric Surgery-2 is
      a multicenter, prospective cohort study of adults undergoing first-time bariatric
      surgery as part of routine clinical care at 10 U.S. hospitals. Recruitment
      occurred between 2005 and 2009. Participants completed preoperative and annual
      postsurgical assessments for up to 7 years until January 2015. This report was
      restricted to women 18-44 years old with no history of menopause, hysterectomy,
      or estrogen and progesterone therapy. Primary outcomes were self-reported
      contraceptive practices, overall conception rate, and early (less than 18 months)
      postsurgical conception. Contraceptive practice (no intercourse, protected
      intercourse, unprotected intercourse, or tried to conceive) was classified based
      on the preceding year. Conception rates were determined from self-reported
      pregnancies. RESULTS: Of 740 eligible women, 710 (95.9%) completed follow-up
      assessment(s). Median (interquartile range) preoperative age was 34 (30-39)
      years. In the first postsurgical year, 12.7% (95% CI 9.4-16.0) of women had no
      intercourse, 40.5% (95% CI 35.6-45.4) had protected intercourse only, 41.5% (95%
      CI 36.4-46.6) had unprotected intercourse while not trying to conceive, and 4.3%
      (95% CI 2.4-6.3) tried to conceive. The prevalence of the first three groups did
      not significantly differ across the 7 years of follow-up (P for all >.05);
      however, more women tried to conceive in the second year (13.1%, 95% CI 9.3-17.0;
      P<.001). The conception rate was 53.8 (95% CI 40.0-71.1) per 1,000 woman-years
      across follow-up (median [interquartile range] 6.5 [5.9-7.0] years); 42.3 (95% CI
      30.2-57.6) per 1,000 woman-years in the 18 months after surgery. Age (adjusted
      relative risk 0.41 [95% CI 0.19-0.89] per 10 years, P=.03), being married or
      living as married (adjusted relative risk 4.76 [95% CI 2.02-11.21], P<.001), and
      rating future pregnancy as important preoperatively (adjusted relative risk 8.50
      [95% CI 2.92-24.75], P<.001) were associated with early conception. CONCLUSIONS:
      Postsurgical contraceptive use and conception rates do not reflect
      recommendations for an 18-month delay in conception after bariatric surgery.
      CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00465829.

PMID- 29016508
TI  - Prophylactic Negative Pressure Wound Therapy for Obese Women After Cesarean
      Delivery: A Systematic Review and Meta-analysis.
AB  - OBJECTIVE: To summarize available studies on wound complication outcomes after
      prophylactic negative pressure wound therapy for obese women (body mass index 30
      or greater). DATA SOURCES: We conducted a systematic review and meta-analysis
      using electronic database search (PubMed, Cumulative Index to Nursing and Allied
      Health Literature, EMBASE, Google scholar, and Web of Science), Cochrane, and
      trial registries including ClinicalTrials.gov. METHODS OF STUDY SELECTION: We
      conducted an electronic search of research articles from 1966 to January 2017 for
      randomized controlled trials (RCTs), prospective cohort, and retrospective cohort
      studies of negative pressure wound therapy compared with standard dressing after
      cesarean delivery among obese women. Our primary outcome was defined as a
      composite of wound complication, including wound or surgical site infection,
      cellulitis, seroma, hematoma, wound disruption, or dehiscence. For cohort studies
      and RCTs, we performed a descriptive systematic review. For available RCTs, we
      performed a meta-analysis and pooled risk ratios using a random-effects model. We
      assessed for heterogeneity using chi test for heterogeneity and I test. We
      assessed for publication bias using a funnel plot. TABULATION, INTEGRATION, AND
      RESULTS: Of 10 studies meeting eligibility criteria, five were RCTs and five were
      cohort studies. Results of cohort studies were varied; however, all had a high
      potential for selection bias. In the meta-analysis, there was no difference in
      primary composite outcome among those women with negative pressure wound therapy
      (16.8%) compared with those who had standard dressing (17.8%) (risk ratio 0.97,
      95% CI 0.63-1.49). There was no statistically significant heterogeneity (chi test
      4.80, P=.31, I=17%). CONCLUSION: Currently available evidence does not support
      negative pressure wound therapy use among obese women for cesarean wound
      complication prevention. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: International
      prospective register of systematic reviews, 42016033948.

PMID- 29016509
TI  - Maternal Vascular Malperfusion and Adverse Perinatal Outcomes in Low-Risk
      Nulliparous Women.
AB  - OBJECTIVE: To evaluate the disease burden of placental maternal vascular
      malperfusion pathology in a low-risk nulliparous population and test the
      hypothesis that a multiparameter model in the second trimester can predict
      maternal vascular malperfusion with high precision. METHODS: A single-center,
      prospective cohort study was conducted in healthy nulliparous women. Maternal
      vascular malperfusion disease burden was estimated by incidence, relative risk
      (RR), and population-attributable risk percent. Maternal risk factors, serum
      biomarkers, Doppler, and placental morphologic ultrasonography were examined in
      isolation and in combination for prediction of this placental pathology. RESULTS:
      The incidence of maternal vascular malperfusion pathology was 8.4% (72/856).
      Women with pathology had higher risk of preeclampsia (8.33% compared with 1.79%;
      RR 4.67, 95% CI 1.85-11.77%; population-attributable risk 23.6%, 95% CI 16.9
      31.6%), small for gestational age (SGA) (47.22% compared with 9.45%; RR 5.00, 95%
      CI 3.6-6.93%; population-attributable risk 25.2%, 95% CI 22.1-28.5%), and the
      composite of adverse outcomes (defined as SGA or preeclampsia) (47.22% compared
      with 10.59%; RR 4.46, 95% CI 3.25-6.13; population-attributable risk 22.5%, 95%
      CI 19.8-25.5%). The combination of parameters was superior to individual
      modalities alone in predicting maternal vascular malperfusion, but achieved only
      moderate precision (area under the curve 0.77, 95% CI 0.71-0.84). CONCLUSION: One
      in 12 healthy nulliparous women develop maternal vascular malperfusion placental
      pathology, and these pregnancies had a 4.5 times higher risk of developing
      preeclampsia or delivering a SGA neonate compared with those without this
      pathology. A multiparameter model achieved modest precision to predict placental
      maternal vascular malperfusion. Importantly, in low-risk pregnancies, maternal
      vascular malperfusion accounts for one fourth of pregnancy outcomes with SGA or
      preeclampsia. The low population-attributable risk of this placental pathology
      for SGA and preeclampsia illustrates the importance of discovering novel
      associations to reduce the disease burden of these pregnancy complications.

PMID- 29016511
TI  - Change in Surgical Practice for Women With Leiomyomas After the U.S. Food and
      Drug Administration Morcellator Safety Communication.
AB  - OBJECTIVE: To evaluate the association between the U.S. Food and Drug
      Administration (FDA) communication discouraging use of power morcellators on
      changes in surgical practice for women with uterine leiomyomas. METHODS: This is
      a cross-sectional study using data from 2013 to 2014 in the Healthcare Cost and
      Utilization Project State Inpatient and State Ambulatory Surgical Databases from
      Arizona, Florida, Kentucky, and New Jersey. Women with a diagnosis of leiomyomas
      who underwent hysterectomy or myomectomy were included in the analysis.
      Multivariable models were used to assess changes in the proportion of
      hysterectomies performed laparoscopically, vaginally, or by laparotomy in the 15
      months before the FDA safety communication in April 2013 (January 2013 to March
      2014) to the 9 months after the FDA communication (April to December 2014).
      Changes in the proportion of women who underwent myomectomy compared with
      hysterectomy were also evaluated during this time period. RESULTS: There were
      77,637 hysterectomy and myomectomy cases analyzed from states with both inpatient
      and ambulatory surgery data; 59% of patients were outpatients. Overall, there was
      a 4% (95% CI 3.2-4.8%) decrease in the use of laparoscopic hysterectomy for
      treatment of uterine leiomyomas from 62% of all hysterectomies before the FDA
      communication on morcellation to 58% afterward. Changes in surgical practice were
      more pronounced in the inpatient compared with outpatient setting; inpatient
      laparoscopic hysterectomy decreased by 7% (95% CI 6.1-7.9%) from 24% to 17% of
      all hysterectomies with an accompanying increase in abdominal hysterectomy of 8%
      (95% CI 6.7-8.6%) from 71% to 79%. There were no significant changes in the
      proportion of women with leiomyomas who underwent myomectomy compared with
      hysterectomy. CONCLUSION: The FDA communication discouraging the use of power
      morcellators was associated with a decline in laparoscopy to perform
      hysterectomy, particularly in the inpatient setting. There was no change in the
      selection of myomectomy compared with hysterectomy for leiomyoma treatment after
      the FDA communication.

PMID- 29016510
TI  - Comparative Effectiveness of Uterine Leiomyoma Procedures Using a Large Insurance
      Claims Database.
AB  - OBJECTIVE: To compare risk of reintervention, long-term clinical outcomes, and
      health care utilization among women who have bulk symptoms from leiomyoma and who
      underwent the following procedures: hysterectomy, myomectomy, uterine artery
      embolization, and magnetic resonance-guided, focused ultrasound surgery. METHODS:
      This was a retrospective analysis of administrative claims from a large U.S.
      commercial insurance database. Women aged 18-54 years undergoing any of the
      previously mentioned leiomyoma procedures between 2000 and 2013 were included. We
      assessed the following outcome measures: risk of reintervention between uterine
      sparing procedures, risk of other surgical procedures or complications of the
      index procedure, 5-year health care utilization, pregnancy rates, and
      reproductive outcomes. Propensity score matching along with Cox proportional
      hazard models were used to adjust for differences in baseline characteristics
      between study cohorts. RESULTS: Among the 135,522 study-eligible women with mean
      follow-up of 3.4 years, hysterectomy was the most common first-line procedural
      therapy (111,324 [82.2%]) followed by myomectomy (19,965 [14.7%]), uterine artery
      embolization (4,186 [3.1%]) and magnetic resonance-guided focused ultrasound
      surgery (47 [0.0003%]). Small but statistically significant differences were
      noted for uterine artery embolization and myomectomy in reintervention rate
      (17.1% compared with 15.0%, P=.02), subsequent hysterectomy rates (13.2% compared
      with 11.1%, P<.01) and subsequent complications from index procedures (18.1%
      compared with 24.6%, P<.001). During follow-up, women undergoing myomectomy had
      lower leiomyoma-related health care utilization, but had higher all-cause
      outpatient services. Pregnancy rates were 7.5% and 2.2% among myomectomy and
      uterine artery embolization cohorts, respectively (P<.001) with both cohorts
      having similar rates of adverse reproductive outcome (69.4%). CONCLUSIONS:
      Although the overwhelming majority of women having leiomyoma with bulk symptoms
      underwent hysterectomy as their first treatment procedure, among those undergoing
      uterine-sparing index procedures, approximately one seventh had a reintervention,
      and one tenth ended up undergoing hysterectomy during follow-up. Compared with
      women undergoing myomectomy, women undergoing uterine artery embolization had a
      higher risk of reintervention, lower risk of subsequent complications, but
      similar rate of adverse reproductive outcomes.

PMID- 29016512
TI  - Trial of Labor Compared With Cesarean Delivery in Superobese Women.
AB  - OBJECTIVE: To examine whether labor compared with planned cesarean delivery is
      associated with increased maternal and neonatal morbidity. METHODS: We conducted
      a retrospective cohort study of all women with body mass indexes (BMIs) at
      delivery of 50 or greater delivering a live fetus at 34 weeks of gestation of
      greater between January 1, 2008, and December 31, 2015. Pregnancies with multiple
      gestations and major fetal anomalies were excluded. The primary outcome was a
      composite of maternal and neonatal morbidity and was estimated to be 50% in
      superobese women based on institutional data. A sample size of 338 women
      determined the study period and was selected to show a 30% difference in the
      incidence of the primary outcome between the two groups. Multivariate logistic
      regression adjusted for potential confounders. RESULTS: There were 344 women with
      BMIs of 50 or greater who met eligibility criteria, of whom 201 (58%) labored and
      143 (42%) underwent planned cesarean delivery. Women who labored were younger,
      more likely to be nulliparous, and less likely to have pre-existing diabetes.
      Among women who labored, 45% underwent a cesarean delivery, most commonly for
      labor arrest (61%) or nonreassuring fetal status (28%). Composite maternal and
      neonatal morbidity was reduced among women who labored even after adjusting for
      age, parity, pre-existing diabetes, and prior cesarean delivery (adjusted odds
      ratio 0.42, 95% CI 0.24-0.75). In the subgroup of women (n=234) who underwent a
      cesarean delivery, whether planned (n=143) or after labor (n=91), there were no
      differences in maternal and neonatal morbidity except that severe maternal
      morbidity was increased in women (n=12) who labored (8.8% compared with 2.1%,
      relative risk 4.2, 95% CI 1.14-15.4). CONCLUSION: Despite high rates of cesarean
      delivery in women with superobesity, labor is associated with lower composite
      maternal and neonatal morbidity. Severe maternal morbidity may be higher in women
      who require a cesarean delivery after labor.

PMID- 29016513
TI  - Emergency Department Care in the Postpartum Period: California Births, 2009-2011.
AB  - OBJECTIVE: To use population data to identify patient characteristics associated
      with a postpartum maternal emergency department visit within 90 days of discharge
      after birth. METHODS: This retrospective cross-sectional study analyzed linked
      maternal discharge and emergency department data for all live California births
      from 2009 to 2011. The primary outcome was at least one emergency department
      visit within 90 days of hospital discharge after birth. Secondary outcomes
      included three or more visits within 90 days ("high utilization") and inpatient
      readmission. Independent variables included demographics (age, race or ethnicity,
      payer, income) and clinical characteristics (length of stay, antepartum
      complications, mode of delivery, and severe maternal morbidity at delivery).
      Multilevel logistic regression identified variables associated study outcomes; we
      validated the predictive model with a split-sample approach and receiver
      operating characteristic curve analysis. RESULTS: Of 1,071,232 deliveries
      included, 88,674 women (8.3%) visited the emergency department at least once in
      the 90 days after delivery discharge. Emergency department use was significantly
      associated with Medicaid insurance (adjusted odds ratio [OR] 2.15, 95% CI 2.08
      2.21), age younger than 20 years (adjusted OR 2.08, 95% CI 1.98-2.19), severe
      maternal morbidity at delivery (adjusted OR 1.58, 95% CI 1.49-1.71), antepartum
      complications (adjusted OR 1.46, 95% CI 1.42-1.50), and cesarean delivery
      (adjusted OR 1.40, 95% CI 1.37-1.44). Approximately one fifth of visits occurred
      within 4 days of discharge, and more than half were within 3 weeks. High
      utilizers comprised 0.5% of the entire sample (5,171 women) and only 1.2% of
      women presenting for emergency department care were readmitted. Receiver
      operating curve model analysis using the validation sample supported predictive
      accuracy for postpartum emergency department use (area under the curve=0.95).
      CONCLUSION: One in 12 California women visited the emergency department in the
      first 90 days after postpartum discharge. Women at increased risk for postpartum
      emergency department use per our validated model (eg, low income, birth
      complications) may benefit from earlier scheduled postpartum visits.

PMID- 29016514
TI  - Disparities in Care for Publicly Insured Women With Pregestational Diabetes.
AB  - OBJECTIVE: To investigate the association among public health insurance,
      preconception care, and pregnancy outcomes in pregnant women with pregestational
      diabetes. METHODS: This is a retrospective cohort of pregnant women with
      pregestational type 1 or type 2 diabetes from 2006 to 2011 in Massachusetts-a
      state with universal insurance coverage since 2006. Women delivering after 24
      weeks of gestation and receiving endocrinology and obstetric care in a
      multidisciplinary clinic were included. Rates of preconception consultation, our
      primary outcome of interest, were then compared between publicly and privately
      insured women. We used univariate analysis followed by logistic regression to
      compare receipt of preconception consultation and other secondary diabetes care
      measures and pregnancy outcomes according to insurance status. RESULTS: Fifty
      four percent (n=106) of 197 women had public insurance. Publicly insured women
      were younger (median age 30.4 compared with 35.3 years, P<.01) with lower rates
      of college education (12.3% compared with 45.1%, P<.01). Women with public
      insurance were less likely to receive a preconception consult (5.7% compared with
      31.9%, P<.01), had lower rates of hemoglobin A1C less than 6% at the onset of
      pregnancy (37.2% compared with 58.4%, P=.01), and experienced higher rates of
      pregnancies affected by congenital anomalies (10.4% compared with 2.2%, P=.02)
      compared with those with private insurance. In adjusted analyses controlling for
      educational attainment, maternal age, and body mass index, women with public
      insurance were less likely to receive a preconception consult (adjusted odds
      ratio [OR] 0.21, 95% CI 0.08-0.58), although the odds of achieving the target
      hemoglobin A1C (adjusted OR 0.45, 95% CI 0.20-1.02) and congenital anomaly
      (adjusted OR 2.23, 95% CI 0.37-13.41) were similar after adjustment. CONCLUSION:
      Despite continuous access to health insurance, publicly insured women were less
      likely than privately insured women to receive a preconception consult-an
      evidence-based intervention known to improve pregnancy outcomes. Improving use of
      preconception care among publicly insured women with diabetes is critical to
      reducing disparities in outcomes.

PMID- 29016517
TI  - Pediatric Poisonings in a Rural Ugandan Emergency Department.
AB  - OBJECTIVE: This study aims to describe pediatric poisonings presenting to a rural
      Ugandan emergency department (ED), identifying demographic factors and causative
      agents. METHODS: This retrospective study was conducted in the ED of a rural
      hospital in the Rukungiri District of Uganda. A prospectively collected quality
      assurance database of ED visits was queried for poisonings in patients under the
      age of 5 who were admitted to the hospital. Cases were included if the chief
      complaint or final diagnosis included anything referable to poisoning, ingestion,
      or intoxication, or if a toxicologic antidote was administered. The database was
      coded by a blinded investigator, and descriptive statistics were performed.
      RESULTS: From November 9, 2009, to July 11, 2014, 3428 patients under the age of
      5 were admitted to the hospital. A total of 123 cases (3.6%) met the inclusion
      criteria. Seventy-two patients were male (58.5%). The average age was 2.3 (SD,
      0.97) years with 45 children (36.6%) under the age of 2 years. There were 19
      cases (15.4%) lost to 3-day follow-up. The top 3 documented exposures responsible
      for pediatric poisonings were cow tick or organophosphates (36 cases, 29.2%),
      general poison or drug overdose (26 cases, 21.1%), and paraffin or hydrocarbon
      (24 cases, 19.5%).Of the admitted patients, 1 died in the ED and 2 died at 72
      hour follow-up, for an overall 72-hour mortality of 2.4%. Patients who died were
      exposed to iron, cow tick, and rat poison. CONCLUSIONS: Pediatric poisoning
      affects patients in rural sub-Saharan Africa. The mortality rate at one rural
      Ugandan hospital was greater than 2%.

PMID- 29016515
TI  - Performance Measures for Contraceptive Care: A New Tool to Enhance Access to
      Contraception.
AB  - Contraception is an essential health service for reducing unintended pregnancy
      rates, improving health outcomes, and reducing health care costs. However,
      contraceptive services may not consistently provide access to the full method mix
      and to patient-centered care. Improving the quality of contraceptive care is a
      critical strategy to improve contraceptive use, health outcomes, and the patient
      experience of care. We here describe the three National Quality Forum-endorsed
      performance measures for contraceptive care, which are intended to monitor 1)
      provision of most and moderately effective methods, 2) access to long-acting
      reversible contraception, and 3) provision of most and moderately effective
      methods and access to long-acting reversible contraception after childbirth.
      These contraceptive care measures are designed to ensure that contraceptive care
      is accessible and offers the full spectrum of methods. Payers, health care
      systems, public agencies, and researchers could all monitor these performance
      measures for different populations. We describe the crucial role of clinicians in
      disseminating and using the contraceptive care performance measures for quality
      improvement. We describe ongoing efforts to improve contraceptive care quality,
      including the development of measures to monitor other dimensions of quality such
      as the safety and patient-centeredness of care. Thirty-eight million women at
      risk of unintended pregnancy are counting on us to improve the quality of family
      planning care in the United States and ensure that all women have the resources
      and tools to make free, informed choices about whether and when to become
      pregnant.

PMID- 29016516
TI  - Barriers to Effective Teamwork Relating to Pediatric Resuscitations: Perceptions
      of Pediatric Emergency Medicine Staff.
AB  - BACKGROUND: In the pediatric emergency department (PED), resuscitations require
      medical teams form ad hoc, rarely communicating beforehand. Literature has shown
      that the medical community has deficiencies in communication and teamwork.
      However, we as medical providers do not know or understand the perceived barriers
      of our colleagues. Physicians may perceive a barrier that is different from
      nurses, respiratory therapists, pharmacists, or technicians. Perhaps we do not
      know in which area of teamwork and communication we are deficient. Only when we
      understand the perceptions of our fellow coworkers can we take steps toward
      improvement in quality resuscitations and therefore patient safety. OBJECTIVE:
      The primary objectives of this study were to describe and understand the
      perceived barriers to effective communication and teamwork among different
      disciplines forming spontaneous resuscitation teams at a tertiary urban PED and
      to determine if providers of different disciplines perceived these barriers
      differently. METHODS: This was a mixed-methods study conducted in a single,
      tertiary care freestanding children's hospital emergency department. Survey
      questions were iteratively developed to measure the construct of barriers and
      best practices within resuscitation teamwork, which was administered to staff
      among 5 selected roles: physicians, nurses, respiratory technicians, PED
      technicians, and PED pharmacists. It contained open-ended questions to provide
      statements on specific barriers or goals in effective teamwork, as well as a
      priority ranking on 25 different statements on teamwork extracted from the
      literature. From the participant data, 9 core themes related to resuscitation
      teamwork were coalesced using affinity diagramming by the authors. All statements
      from the survey were coded to the 9 core themes by 2 authors, with high
      reliability (kappa = 0.93). Descriptive statistics were used to summarize the
      prevalence of themes mentioned by survey participants. A chi test was used to
      determine differences in prevalence of core themes by role. Rank data for the 25
      statements were converted to a point system (5 points for most important, 4
      points for second most important, etc), and a mixed within-between analysis of
      variance was used to determine the association of role and relative rank.
      RESULTS: There were 125 respondents (62% response rate) who provided 893 coded
      statements. The core theme of communication-in particular, closed-loop
      communication-was the most prevalent theme, although no differences in the
      proportion of themes represented were seen by PED staff of different roles (P =
      0.18). There was a significant effect from the core theme (P = 0.002, partial eta
      = 0.13), with highest priority on team leader performance (mean points out of 5 =
      2.5 +/- 1.9), but neither effect nor interaction with role (P = 0.6, P = 0.7).
      CONCLUSIONS: When answering open-ended questions regarding barriers to effective
      resuscitations, all disciplines perceived communication, particularly closed-loop
      communication, as the primary theme lacking during resuscitations. However, when
      choosing from a list of themes, all groups except physicians perceived
      deficiencies in team leader qualities to be the greatest barrier. We as
      physicians must work on improving our communication and leadership attributes if
      we want to improve the quality of our resuscitations.

PMID- 29016518
TI  - Gastric Drainage in the Treatment of Near-Fatal Food-Induced Anaphylaxis.
AB  - Anaphylaxis should be treated with early administration of intramuscular
      Adrenalin; however, fatalities may still occur even with this therapy. We report
      a patient with near-fatal anaphylaxis due to milk whose symptoms persisted and
      were resistant to any therapeutic attempt; however, the patient had a prompt
      resolution of the anaphylaxis shortly after a nasogastric tube placement with
      gastric drainage, suggesting that this procedure ended the ongoing absorption of
      additional allergen from the gastrointestinal tract. We suggest that nasogastric
      drainage of gastric contents should be considered as part of the therapy in
      severe food-induced anaphylaxis.

PMID- 29016519
TI  - Clinical Decision Rule to Identify Orbital Wall Fracture Among Children:
      Retrospective Derivation and Validation Study.
AB  - OBJECTIVES: Head and face injuries are leading causes of emergency department
      visits in children. There is yet no clinical decision rule on face CT such as
      pediatric head CT rules. The goal was to develop and validate a clinical decision
      rule for identifying orbital wall fractures in children with periorbital trauma
      in the emergency department. METHODS: This was a retrospective derivation and
      validation study. Children younger than 18 years who underwent orbit CT after
      periorbital trauma were included between January 2011 and December 2013 in 3
      emergency centers. Among 16 candidate clinical variables, 13 clinical signs and
      symptoms were selected as clinical predictors. For the fracture model, these
      clinical predictors were analyzed by 3-fold cross-validation. Diagnostic
      performance was assessed using the area under the receiver operating
      characteristic (AUROC) curve in both cohorts. RESULTS: Four variables (orbital
      rim tenderness, periorbital ecchymosis, painful extraocular movement, and
      nausea/vomiting) had the best predictive model with the highest AUROC value. The
      AUROC values for fracture prediction were 0.793 (95% confidence interval, 0.741
      0.844) and 0.809 (95% confidence interval, 0.742-0.877) in the derivation cohort
      and validation cohort, respectively. The sensitivity and negative predictive
      values were 96.4% and 93.4%, respectively, in the derivation cohort, and 97.8%
      and 98.1%, respectively, in the validation cohort. The sum of these scores ranged
      from 0 to 4. Patients with a sum of scores of 1 or higher showed significantly
      increased risk for fracture. CONCLUSIONS: The 4-variable predictive model can be
      useful for finding clinically important orbital wall fractures in children.

PMID- 29016520
TI  - Episcleral Venous Outflow: A Potential Outcome Marker for iStent Surgery.
AB  - PURPOSE: (1) To propose the use of episcleral venous outflow (EVO) as an outcome
      marker of iStent surgery, and an EVO grading scale. (2) To determine the
      association of EVO with: (a) postoperative intraocular pressure (IOP) and
      medication burden; (b) iStent patency status. PATIENTS AND METHODS: Retrospective
      cohort study including 151 glaucomatous eyes having undergone iStent
      phacoemulsification surgery. Demographic and preoperative data (IOP, number of
      antiglaucoma medications, glaucoma type and stage, maximal IOP) were collected.
      Postoperatively, were recorded: IOP, number of antiglaucoma medications,
      occurrence of stent malpositioning or obstruction, and EVO scores based on the
      proposed scale (0: no laminar flow; 1+: faint laminar flow; 2+: marked laminar
      flow). A Kruskal-Wallis test determined the association between EVO,
      postoperative IOP, and medication burden. A multivariable-adjusted ordinal
      logistic regression was used for the association with iStent patency status.
      RESULTS: Patients with marked laminar flow (2+) were more likely to have a lower
      IOP (P=0.022) and fewer medications (P=0.009) at 1-year postoperatively than
      those with no laminar flow (0). No difference was found in postoperative IOP and
      number of medications when comparing patients having faint laminar flow (1+) with
      patients from the other 2 EVO categories (0 and 2+). iStent patency was
      associated with greater EVO as opposed to its obstruction (odds ratio, 4.73; 95%
      confidence interval, 1.74-12.9). No malpositioned stents were noted in our
      cohort. CONCLUSIONS: The use of EVO as an outcome marker of iStent surgery is
      physiologically plausible. The proposed EVO grading scale is simple, comprises
      few categories, and is easily applicable in an in-office setting. The results of
      this study suggest this scale could be useful in the assessment of iStent
      functionality and encourage its further investigation in prospective studies.

PMID- 29016521
TI  - Glaucoma Diagnostic Capabilities of Foveal Avascular Zone Parameters Using
      Optical Coherence Tomography Angiography According to Visual Field Defect
      Location.
AB  - PURPOSE: To assess the diagnostic ability of foveal avascular zone (FAZ)
      parameters to discriminate glaucomatous eyes with visual field defects (VFDs) in
      different locations (central vs. peripheral) from normal eyes. PATIENTS AND
      METHODS: Totally, 125 participants were separated into 3 groups: normal (n=45),
      glaucoma with peripheral VFD (PVFD, n=45), and glaucoma with central VFD (CVFD,
      n=35). The FAZ area, perimeter, and circularity and parafoveal vessel density
      were calculated from optical coherence tomography angiography images. The
      diagnostic ability of the FAZ parameters and other structural parameters was
      determined according to glaucomatous VFD location. Associations between the FAZ
      parameters and central visual function were evaluated. RESULTS: A larger FAZ area
      and longer FAZ perimeter were observed in the CVFD group than in the PVFD and
      normal groups. The FAZ area, perimeter, and circularity were better in
      differentiating glaucomatous eyes with CVFDs from normal eyes [areas under the
      receiver operating characteristic curves (AUC), 0.78 to 0.88] than in
      differentiating PVFDs from normal eyes (AUC, 0.51 to 0.64). The FAZ perimeter had
      a similar AUC value to the circumpapillary retinal nerve fiber layer and macular
      ganglion cell-inner plexiform layer thickness for differentiating eyes with CVFDs
      from normal eyes (all P>0.05, the DeLong test). The FAZ area was significantly
      correlated with central visual function (beta=-112.7, P=0.035, multivariate
      linear regression). CONCLUSIONS: The FAZ perimeter had good diagnostic capability
      in differentiating glaucomatous eyes with CVFDs from normal eyes, and may be a
      potential diagnostic biomarker for detecting glaucomatous patients with CVFDs.

PMID- 29016522
TI  - Spontaneous Resolution of Delayed Suprachoroidal Hemorrhage in the Single Eye
      Following Needling in Congenital Glaucoma.
AB  - INTRODUCTION: Suprachoroidal hemorrhage (SCH) is a rare, but potentially vision
      threatening event with poor long-term visual prognosis. At present, there is
      disagreement whether surgical intervention or conservative treatment is superior
      in the management. We report on a case of spontaneous resolution of severe SCH
      after needling procedure in the only eye of a young patient with congenital
      glaucoma. CASE PRESENTATION: A 43-year-old woman with congenital glaucoma was
      scheduled for bleb needling in her only eye. Preoperative best-corrected visual
      acuity was 20/40 and intraocular pressure 20 mm Hg. On the third postoperative
      day, she developed a massive delayed SCH with appositional (kissing) choroidal
      bullae and visual acuity was hand motion. Scleral drainage was performed after 10
      days, but did not show a significant decrease of the choroidal swelling and
      further conservative treatment was discussed. After 2 months, choroidal swelling
      had completely resolved, best-corrected visual acuity was 20/50, and intraocular
      pressure was 11 mm Hg. DISCUSSION: Full functional recovery and decrease of
      choroidal swelling may be attained with a conservative treatment of massive
      delayed SCH after needling procedure in congenital glaucoma.

PMID- 29016525
TI  - PARACENTRAL ACUTE MIDDLE MACULOPATHY IN SUSAC SYNDROME.
AB  - PURPOSE: To present the first reported case of paracentral acute middle
      maculopathy in association with Susac syndrome. METHOD: Case report. RESULTS: A
      young female patient presented with unilateral sudden loss of vision of her right
      eye to count fingers. There were numerous cotton wool spots in a multifocal
      pattern concentrated around the right macula and optic disk. Clinical examination
      and spectral domain optical coherence tomography imaging were consistent with
      paracentral acute middle maculopathy, and fluorescein angiography showed features
      of retinal arteriole vasculitis. Magnetic resonance imaging demonstrated multiple
      white matter lesions in a pericallosal distribution. High-dose corticosteroid
      therapy was commenced, and visual acuity gradually improved to 6/6 corrected. The
      patient reported hearing impairment and was diagnosed with Susac syndrome for
      which she has responded extremely well to long-term immunosuppressive therapy.
      CONCLUSION: Paracentral acute middle maculopathy can occur in association with
      Susac syndrome. Susac syndrome may present only with multifocal retinal ischemia,
      and such patients with paracentral acute middle maculopathy should be checked for
      characteristic magnetic resonance imaging lesions and hearing loss.

PMID- 29016523
TI  - Brief Report: PrEP Use During Periods of HIV Risk Among East African Women in
      Serodiscordant Relationships.
AB  - BACKGROUND: Pre-exposure prophylaxis (PrEP) is efficacious for African women at
      risk for HIV, but data on adherence outside clinical trials are sparse. We
      describe the persistence and execution of PrEP use among women participating in a
      large open-label PrEP demonstration project, particularly during periods of HIV
      risk. SETTING AND METHODS: Three hundred ten HIV-uninfected women in HIV
      serodiscordant couples in Kenya and Uganda were offered and accepted PrEP.
      Electronic monitoring caps were used to measure daily PrEP adherence. Time on
      PrEP while at risk for HIV (when the HIV-infected partner was on antiretroviral
      therapy <6 months) and weekly adherence while on PrEP were calculated and
      compared among older and younger (<25 years old) women. RESULTS: As defined
      above, women were at risk for HIV for an average of 361 days; 54% took PrEP
      during their entire risk period and 24% stopped but restarted PrEP during their
      risk period. While on PrEP, women took >=6 doses/wk for 78% of weeks [67% of
      weeks for women aged <25 years, 80% of weeks for women aged >=25 years (P <
      0.001)], and >=4 doses for 88% of weeks [80% for those <25, 90% for those >=25,
      (P < 0.001)]. Compared with historical, risk-matched controls, HIV incidence was
      reduced 93% (95% confidence interval: 77% to 98%) for all women and 91% (95%
      confidence interval: 29% to 99%) among women aged <25 years. CONCLUSION: Women,
      including young women, in HIV-serodiscordant couples took PrEP successfully over
      sustained periods of risk. Although young women had lower adherence than older
      women, they achieved strong protection, which suggests that women can align PrEP
      use to periods of risk and imperfect adherence can still provide substantial
      benefit.

PMID- 29016527
TI  - ACUTE MACULAR NEURORETINOPATHY AND PERIPHERAL RETINAL VASCULAR ABNORMALITIES IN A
      PATIENT BORN HIV SEROPOSITIVE.
AB  - PURPOSE: To describe the case of a born HIV seropositive woman who developed
      outer retinal alterations secondary to vascular abnormalities in the perimacular
      region and in the periphery of both eyes. METHODS: Case report. RESULTS: A 21
      year-old woman born HIV seropositive was referred for a routinary visit. Her best
      corrected visual acuity was 20/20 in both eyes, and during the visit, only mild
      superotemporal metamorphopsia in the left eye was reported. Multimodal imaging
      disclosed findings consistent with acute macular neuroretinopathy such as reddish
      brown lesions at fundus examination and disruption of ellipsoid zone at spectral
      domain optical coherence tomography. Peripheral vascular alterations were also
      noted at fluorescein angiography. CONCLUSION: Several associations or risk
      factors have been identified in patients with acute macular neuroretinopathy,
      including oral contraceptives, epinephrine/ephedrine, or systemic shock. To the
      best of our knowledge, this is the first case describing peripheral vascular
      alterations and acute macular neuroretinopathy in association with HIV
      seropositivity at birth.

PMID- 29016526
TI  - ENLARGEMENT OF SCLEROCHOROIDAL CALCIFICATIONS: MULTIMODAL IMAGING UPDATE.
AB  - PURPOSE: To report the multimodal imaging and enlargement of sclerochoroidal
      calcifications over a 10-year period. METHODS: Case report of a 74-year-old white
      man who presented for routine follow-up and was found to have yellow
      chorioretinal lesions in the right eye. RESULTS: Multimodal imaging was performed
      and confirmed sclerochoroidal calcifications. Comparison of fundus photography
      over a 10-year period demonstrated growth of preexisting lesions and the
      development of new lesions in the right eye. CONCLUSION: Over time, this patient
      developed new sclerochoroidal calcifications and enlargement of preexisting
      calcifications. We, therefore, recommend regular follow-up with periodic
      multimodal imaging for these patients.

PMID- 29016528
TI  - TRANSTHYRETIN V30M FAMILIAL AMYLOIDOSIS PRESENTING AS ISOLATED RETINAL
      ANGIOPATHY.
AB  - PURPOSE: To describe a patient with confirmed transthyretin V30M form of familial
      amyloidosis who presented initially with isolated retinal angiopathy. METHODS:
      Retrospective chart review. RESULTS: A 66-year-old woman presented with bilateral
      retinal angiopathy. Extensive workup for an infectious, inflammatory, or
      hypercoagulable cause was unrevealing. The patient subsequently developed
      bilateral neovascularization of the optic nerve and iris complicated by recurrent
      vitreous hemorrhages, which were treated with intravitreal bevacizumab and
      panretinal photocoagulation. The development of cardiac and gastrointestinal
      symptoms 5 years after presentation led to tissue biopsies that revealed both
      Congo red staining and apple-green birefringence in polarized light, confirming
      the diagnosis of systemic amyloidosis. Sequencing of the transthyretin gene
      confirmed the patient to be heterozygous for the common amyloidogenic V30M
      mutation. CONCLUSION: The common transthyretin V30M form of familial amyloidotic
      polyneuropathy can rarely present with retinal angiopathy. Recurrent vitreous
      hemorrhages were treated successfully with intravitreal bevacizumab and
      panretinal photocoagulation.

PMID- 29016524
TI  - Incidence of Tuberculosis Among HIV-Positive Individuals Initiating
      Antiretroviral Treatment at Higher CD4 Counts in the HPTN 071 (PopART) Trial in
      South Africa.
AB  - INTRODUCTION: Antiretroviral treatment (ART) guidelines recommend life-long ART
      for all HIV-positive individuals. This study evaluated tuberculosis (TB)
      incidence on ART in a cohort of HIV-positive individuals starting ART regardless
      of CD4 count in a programmatic setting at 3 clinics included in the HPTN 071
      (PopART) trial in South Africa. METHODS: A retrospective cohort analysis of HIV
      positive individuals aged >=18 years starting ART, between January 2014 and
      November 2015, was conducted. Follow-up was continued until 30 May 2016 or
      censored on the date of (1) incident TB, (2) loss to follow-up from HIV care or
      death, or (3) elective transfer out; whichever occurred first. RESULTS: The study
      included 2423 individuals. Median baseline CD4 count was 328 cells/MUL
      (interquartile range 195-468); TB incidence rate was 4.41/100 person-years (95%
      confidence interval [CI]: 3.62 to 5.39). The adjusted hazard ratio of incident TB
      was 0.27 (95% CI: 0.12 to 0.62) when comparing individuals with baseline CD4 >500
      and <=500 cells/MUL. Among individuals with baseline CD4 count >500 cells/MUL,
      there were no incident TB cases in the first 3 months of follow-up. Adjusted
      hazard of incident TB was also higher among men (adjusted hazard ratio 2.16; 95%
      CI: 1.41 to 3.30). CONCLUSIONS: TB incidence after ART initiation was
      significantly lower among individuals starting ART at CD4 counts above 500
      cells/MUL. Scale-up of ART, regardless of CD4 count, has the potential to
      significantly reduce TB incidence among HIV-positive individuals. However, this
      needs to be combined with strengthening of other TB prevention strategies that
      target both HIV-positive and HIV-negative individuals.

PMID- 29016530
TI  - REABSORPTION OF ACQUIRED VITELLIFORM LESIONS IN VITREOMACULAR DISORDERS AFTER
      VITRECTOMY.
AB  - PURPOSE: To describe cases of reabsorption of subretinal acquired vitelliform
      material (acquired vitelliform lesion [AVL]) associated with vitreomacular
      disorders after 25-gauge pars plana vitrectomy and peeling of internal limiting
      membrane. METHODS: Data of consecutive patients who underwent 25-gauge
      transconjunctival pars plana vitrectomy for vitreomacular disorders at the
      Department of Ophthalmology of the University Hospital of Brussels (Belgium) were
      collected. Patients featuring AVL on fundus examination or on spectral domain
      optical coherence tomography were recruited. Patients were followed up for 12
      months after surgery. RESULTS: Four eyes of three consecutive white patients
      presenting AVL were included. Three cases were affected by macular pucker,
      whereas one case featured vitreomacular traction syndrome. Progressive flattening
      of the AVL after surgery was observed in three eyes of three patients. One eye
      did not show any resorption of the submacular accumulation. In two eyes, atrophy
      of the retinal pigment epithelium and the outer retinal layers was observed along
      with resolution of the AVL, with significant worsening of visual acuity
      postoperatively. CONCLUSION: The outcome of surgery in cases of submacular AVL
      associated with vitreomacular interface syndromes could be heterogeneous and may
      depend on the duration of the disease and baseline optical coherence tomography
      characteristics of the lipofuscin accumulation.

PMID- 29016529
TI  - NOVEL CONE DYSTROPHY WITH CENTRAL ELLIPSOID ZONE LOSS ASSOCIATED WITH HUMAN
      RETINAL FASCIN GENE (FSCN2) MUTATION.
AB  - PURPOSE: To report the first case of a cone dystrophy with central ellipsoid zone
      loss associated with a mutation in the human retinal fascin gene (FSCN2).
      METHODS: Multimodal retinal imaging findings including spectral domain optical
      coherence tomography and fundus autofluorescence are presented. The results of
      functional testing and mutational analysis are also discussed. PATIENTS: Single
      patient with a diagnosis of cone dystrophy. RESULTS: Spectral domain optical
      coherence tomography imaging illustrated central loss of the ellipsoid zone band
      in each eye. Full-field and multifocal electroretinogram testing confirmed a
      diagnosis of cone dystrophy in a 35-year-old male patient. Subsequent cone
      dystrophy genetic panel identified a novel mutation (p.Pro406Leu:c.1217C>T) in
      the FSCN2 gene. CONCLUSION: This is the first case report of a patient diagnosed
      with cone dystrophy associated with a novel mutation in the FSCN2 gene. FSCN2
      genetic testing should be considered in patients with central ellipsoid loss and
      cone dystrophy, especially as specific gene therapy treatments emerge in the
      future.

PMID- 29016531
TI  - Myocardial preload alters central pressure augmentation through changes in the
      forward wave.
AB  - OBJECTIVE: Augmentation index (AIx) is often used to quantify the contribution of
      wave reflection to central pulse pressure. Recent studies have challenged this
      view by showing how contractility-induced changes in the forward pressure wave
      can markedly impact AIx. We hypothesized that changes in preload will also affect
      AIx through changes in the forward wave and studied this in two experiments.
      METHODS: Noninvasively obtained aortic pressure was used to study central
      haemodynamics and wave morphology. In the first experiment, we examined the
      effects of head-up tilt with and without unilateral thigh cuff in 12 young
      healthy volunteers (mean age 26 years, 50% men). In the second experiment, we
      examined the effects of active standing in 31 middle-aged patients (mean age 57
      years, 65% men) before and after phlebotomy. RESULTS: Head-up tilt or active
      standing significantly decreased AIx [-17.7 +/- 10.4 percentage point (pp) in the
      young population, -4.7 +/- 12.3 pp in the middle-aged population, both P < 0.05].
      The fall in AIx was associated with increases in HR, diastolic pressure and
      systemic vascular resistance and a decrease in stroke volume (all P < 0.05).
      Inflation of a unilateral thigh cuff reduced the decrease in AIx by 10.7 pp,
      whereas 500 ml of blood loss augmented the fall in AIx by 5.9 pp (both P < 0.05).
      The changes in AIx were related to a preload-induced change in forward pressure
      wave shape (earlier peaking and steeper downstroke). CONCLUSION: Next to
      inotropic and chronotropic effects, preload emerges as another myocardial factor
      that obscures the relation between wave reflection and AIx.

PMID- 29016532
TI  - KCNJ5 mutation as a predictor for resolution of hypertension after surgical
      treatment of aldosterone-producing adenoma.
AB  - OBJECTIVE: To investigate the effect of KCNJ5 mutations on the cure of
      hypertension in patients with aldosterone-producing adenoma (APA) after
      unilateral adrenalectomy. METHODS: Our study included 142 patients with APA, who
      were detected with an endocrinological abnormality and diagnosed with
      hypertension, as confirmed by pathological analysis. We sequenced KCNJ5, ATP1A1,
      ATP2B3, CACNA1D, and CTNNB1 from APA tissue samples, and performed a
      retrospective analysis to determine correlations between wild-type or mutated
      KCNJ5 and patient clinical characteristics. RESULTS: Somatic KCNJ5 mutations were
      identified in 106 of 142 patients with APA, 136 of whom had resolution of
      hyporeninemic-hyperaldosteronemia 1 year after surgery. Of the 136 patients, 81
      patients had resolution of hypertension ('Cured group' vs. 'Improved group'). We
      found increased prevalence of KCNJ5 mutations in the Cured group compared to the
      Improved group (85.2% vs. 60.0%, respectively; P = 0.002), which was associated
      with younger age, shorter duration of hypertension, fewer antihypertensive
      medications, lower BMI, higher aldosterone level, higher estimated glomerular
      filtration rate, and milder vascular complications. In both groups we found that
      harbouring a KCNJ5 mutation, taking fewer antihypertensive medications, and the
      duration of hypertension were independently associated with resolution of
      hypertension by unilateral adrenalectomy. In patients with KCNJ5-mutated APA,
      left ventricular hypertrophy was significantly decreased by surgical treatment in
      patients from either Cured or Improved groups, although those patients with wild
      type KCNJ5 showed no change. CONCLUSIONS: Testing for KCNJ5 mutations in young
      patients with APA may provide a prognostic indication for resolution of
      hypertension and severity of vascular complications.

PMID- 29016533
TI  - Age at natural menopause and hypertension among middle-aged and older Chinese
      women.
AB  - OBJECTIVES: Earlier age at natural menopause has been associated with
      cardiovascular disease in several studies, but evidence of its association with
      hypertension is lacking. We aimed to examine the relationship between age at
      natural menopause and hypertension among middle-aged and older Chinese women.
      METHODS: A total of 13 406 postmenopausal women (mean age 63.5 years) were
      enrolled from the Dongfeng-Tongji cohort study in Hubei province, China. Age at
      natural menopause was self-reported and was categorized into three groups (<=45,
      46-52, or >=53 years). Logistic regression models were used to calculate the odds
      ratios (ORs) and 95% confidence intervals (CIs) for hypertension in relation to
      age at natural menopause. RESULTS: Of the study participants, 6690 (49.9%) women
      were diagnosed as hypertension. The mean age at natural menopause was 49.3 +/-
      3.3 years. After adjustment for potential confounders, the ORs of hypertension
      for women who reached menopause at age 45 or less and 46-52 years were 1.27 (95%
      CI, 1.08, 1.50) and 1.14 (95% CI, 1.01, 1.29), respectively, compared with those
      who reached menopause at age at least 53 years. Each 1-year delay in menopause
      was associated with 2% decrease in prevalence of hypertension (OR, 0.98; 95% CI,
      0.97, 0.99). CONCLUSION: Our findings suggested that earlier age at natural
      menopause was related to prevalence of hypertension independent of potential
      confounders. Identification of women with earlier menopause offers a window of
      opportunity to improve women's health during the postmenopausal years.

PMID- 29016534
TI  - Analysis of the citation of articles published in the European Journal of
      Emergency Medicine since its foundation.
AB  - OBJECTIVES: The aim of this study was to evaluate the evolution of the citation
      of articles from the European Journal of Emergency Medicine (EJEM) from 1994
      (EJEM foundation) to 2015 and identify highly cited articles and their principal
      characteristics and determine a possible correlation between the citations
      counted in different databases. MATERIALS AND METHODS: We obtained the articles
      published in EJEM from 1994 to 2015 in ISI-WoS (main source) and Scopus, Google
      Scholar, and Medline databases (accessory sources). The citations were quantified
      and their annual evolution and the bibliometric indices derived (impact factor
      and SCImago Journal Rank) were evaluated. We identified and analyzed the highly
      cited EJEM articles and evaluated the possible correlation between the citations
      counted for these articles in the databases. RESULTS: Overall, 1705 EJEM articles
      were cited 9422 times in 8122 different articles. The evolution of the global
      citation, impact factor, and SCImago Journal Rank from 1994 to 2015 increased
      significantly. The h-index of EJEM was 30, and 31 articles were considered highly
      cited (>=30 citations), 16.1% of them being clinical trials. By subjects, 22.5%
      corresponded to cardiology, 19.3% to emergency department management, and 12.9%
      to pediatrics; by countries, 81% were from Europe, with Belgian authors
      publishing four (12.9%) highly cited articles, and French, Spanish, British, and
      Swedish authors having three (9.7%) each. Two studies in the EJEM achieved the
      definition of 'citation classics' (more than 100 citations). The number of
      citations in all the databases, except Medline, showed statistically significant
      correlations. CONCLUSION: Citation of EJEM articles has progressively increased
      and EJEM bibliometric indicators have improved; most highly cited articles are
      mainly by European authors.

PMID- 29016536
TI  - Repair of a Full-Thickness Defect of the Lower Eyelid Margin.

PMID- 29016537
TI  - Long-Pulsed Nd: YAG Laser Treatment for Nail Psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory skin disease in which lesions
      display angiogenesis and increased vascularity. OBJECTIVE: The long-pulsed 1,064
      nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treats vascular lesions which
      suggests that it might also be used to treat nail psoriasis. METHODS: Sixteen
      patients (10 males and 6 females) with isolated nail psoriasis or nail with only
      mild cutaneous involvement were enrolled in the study. Nails were treated for 3
      sessions with long-pulsed 1,064-nm Nd:YAG laser once monthly. During the course
      of the treatment, nail bed and matrix Nail Psoriasis Severity Index (NAPSI)
      scores were recorded. RESULTS: The mean baseline NAPSI score was 26 +/- 7.2. The
      means of total NAPSI scores after the first, second, and third treatment sessions
      were as follows: 22 +/- 6.6, 13 +/- 6, and 5.7 +/- 4.3, respectively. The decline
      in NAPSI score was statistically significant. At the end of the 3 treatment
      sessions, both nail bed and matrix lesions significantly responded to Nd:YAG
      laser treatment. CONCLUSION: The Nd:YAG laser is a promising treatment option for
      nail psoriasis.

PMID- 29016535
TI  - Botulinum Toxin in Aesthetic Medicine: Myths and Realities.
AB  - BACKGROUND: Several formulations of Botulinum toxin serotype A (BoNT-A) for
      aesthetic indications are available, with numbers likely to increase.
      Preparations are not interchangeable, based on dose unit comparisons. OBJECTIVE:
      Numerous myths and misconceptions regarding the use of BoNT-A for aesthetic
      indications have arisen, which this review aims to lay to rest. MATERIALS AND
      METHODS: This review assesses evidence for and against each of the most common
      myths regarding BoNT use in aesthetics. RESULTS: BoNT-A neurotoxin/protein
      complexes are irrelevant to the toxin's therapeutic/aesthetic indications. BoNT-A
      neurotoxin/protein complexes do not influence movement from injection site or
      immunogenicity. Any relationship between neutralizing antibody formation and
      clinical response is complex and clinicians should consider other factors that
      may induce an apparent loss of clinical response. Diffusion appears
      predominately, perhaps exclusively, dose dependent. Careful placement and correct
      dosing optimizes likelihood of good outcomes. Manufacturers recommend
      reconstitution of products with sterile nonpreserved saline. However, compelling
      evidence suggests that reconstitution using preserved saline dramatically
      improves patient comfort without compromising efficacy. Several post-treatment
      instructions/restrictions are widely used despite the lack of evidence, but
      muscle activity after injection may be beneficial. Cooling the treatment area
      might hinder BoNT-A translocation and should probably be abandoned. CONCLUSION:
      The existing evidence suggests that experienced users should achieve equivalent
      results regardless of BoNT-A formulation, but additional, well-designed,
      adequately powered, controlled randomized studies should be performed.

PMID- 29016538
TI  - Healing Time Correlates With the Quality of Scaring: Results From a Prospective
      Randomized Control Donor Site Trial.
AB  - BACKGROUND: Scar formation remains a potential problem after surgery or trauma.
      Factors influencing scar tissue have been recognized, most notably healing time
      and wound depth. OBJECTIVE: To examine the association between healing time and
      the quality of scar tissue formation. MATERIALS AND METHODS: Scarring was
      assessed at 3 and 12 months after treatment in an RCT of 219 patients and
      consecutive 438 split-thickness skin graft donor sites. The primary end point of
      the study was healing time and the quality of scar tissue, which was scored by a
      validated scar scale evaluating scar height, surface, and color. RESULTS: The
      mean time of wound healing was 15.8 days, with a mean scar score of 6.89 at 3
      months and 4.66 at 12 months. There was a significant (p < .000001) and linear
      correlation between healing time and scar quality. Of particular note, at 12
      months, all subparameters of the score demonstrated worsening with prolonged time
      to heal. CONCLUSION: The authors could objectively demonstrate that
      epithelialization time is an important factor influencing scar quality. In
      contrast to previous assumptions, this correlation follows linearly. It is
      reasonable then to assume that treatment strategies expediting healing will also
      improve scar outcome.

PMID- 29016539
TI  - Color Doppler Ultrasound Supports Early Diagnosis of Mixed High and Low Risk of
      Recurrence Subtypes in the Same Basal Cell Carcinoma Lesion.

PMID- 29016540
TI  - Deoxycholic Acid Injections for Bra-Line Lipolysis.

PMID- 29016541
TI  - A Novel Treatment of Acne Keloidalis Nuchae by Long-Pulsed Alexandrite Laser.
AB  - BACKGROUND: Acne keloidalis nuchae (AKN) is a dermatological condition
      characterized by follicular-based papules and pustules that later form
      hypertrophic or keloid-like scars. Laser-assisted hair reduction such as 810-nm
      diode laser and 1,064-nm Nd:YAG laser have been used for treating AKN with
      promising results. OBJECTIVE: To evaluate the therapeutic effect and safety of
      alexandrite laser in the treatment of different lesions of AKN. METHODS:
      Seventeen male patients with AKN received 6 sessions of 755-nm alexandrite laser.
      Papule and pustule count, keloidal plaque size, pliability, tenderness, and
      itching were assessed at the fourth session and 4 weeks after the sixth session.
      Patient satisfaction and Dermatology Life Quality Index (DLQI) questionnaire were
      performed at the end of treatment. Patients were followed up for 3 months after
      the final treatment. RESULTS: There was a significant decrease in the mean
      papule, pustule count, keloidal plaque size, and pliability at the fourth and
      sixth laser sessions when compared with baseline. Reduction of the hair density
      in the treated area is the only complication observed, which was accepted by the
      patients because of its reversible course. There was a statistically
      significantly higher percentage of improvement in the early lesions
      (papulopustular) compared with late (keloidal plaque) lesions. By the end of
      laser sessions, DLQI scores were significantly reduced. Temporary hair loss was
      noted in 4 patients in the treated sites. No lesional recurrence was detected in
      the follow-up period. CONCLUSION: Using 755-nm alexandrite laser for treatment of
      AKN is a safe and effective procedure with low recurrence rates. Alexandrite
      laser can significantly improve the quality of life of those patients suffering
      from this disfiguring chronic disorder.

PMID- 29016542
TI  - Long-Term Follow-Up Results of Topical Imiquimod Treatment in Basal Cell
      Carcinoma.
AB  - BACKGROUND: Imiquimod 5% topical cream is approved for treatment of superficial
      basal cell carcinoma (BCC). Data on the long-term efficacy and usage in other BCC
      subtypes are scarce. OBJECTIVE: Evaluation of long-term safety and efficacy of
      topical imiquimod treatment in various BCC subtypes and locations, with
      individualized treatment duration. MATERIALS AND METHODS: Histopathologically
      confirmed BCCs treated solely with topical imiquimod were identified
      retrospectively and included in this study. Clinical and histopathologic tumor
      clearances were the primary end point. After treatment was concluded, patients
      were examined every 3 to 6 months. RESULTS: In total, 24 BCC samples from 22
      patients (F:M = 9:13; mean age: 73.5 years, SD: 10.767) were evaluated. The
      majority of the lesions were located in the head and neck area (83%). Mean
      treatment duration until complete clearance was 15.7 +/- 6.9 weeks (6-28 weeks).
      Imiquimod was discontinued in 3 lesions, due to either clinically or
      histopathologically insufficient response. During follow-up, 2 lesions recurred,
      at 42 and 50 months after treatment. During a mean follow-up time of 72.7 (SD =
      9) months, 79.1% of the lesions were cured without local recurrence. CONCLUSION:
      Although imiquimod is only approved for superficial BCC, treatment success was
      high among the study patients with various histological subtypes, with good long
      term cosmetic results.

PMID- 29016544
TI  - Investigation of the Efficacy and Safety of Topical Vibration Anesthesia to
      Reduce Pain From Cosmetic Botulinum Toxin A Injections in Chinese Patients: A
      Multicenter, Randomized, Self-Controlled Study.
AB  - BACKGROUND: Vibration has been proved to be effective to reduce pain during
      facial cosmetic injections, but it has not been studied in Chinese patients.
      OBJECTIVE: To investigate the efficacy and safety of vibration for pain reduction
      associated with cosmetic botulinum toxin A (BTX-A) injections in Chinese
      patients. MATERIALS AND METHODS: In this prospective, randomized, split-face and
      right-left, self-controlled study, 53 patients received BTX-A injections for
      rhytid reduction, lower face, shoulder, and leg reshaping. Injections were given
      in a split-face and right-left design randomly assigned. A vibration stimulus was
      coadministered with BTX-A injections on one side, whereas the other side received
      BTX-A injections only. Patients completed a questionnaire immediately after
      treatment and were followed up 2 weeks later. A visual analog scale of pain
      sensation was statistically analyzed. RESULTS: The patients experienced both
      clinically and statistically significant pain reduction when a vibration was
      coadministered with injections. Patients reported less pain on the treated side
      compared with the control side. Overall, 75% of patients preferred to receive
      vibration with their next treatment. No adverse events were reported. CONCLUSION:
      Vibration is an effective and safe way to reduce pain during cosmetic BTX-A
      injections and may have applications in other cosmetic procedures.

PMID- 29016543
TI  - Finer Needles Reduce Pain Associated With Injection of Local Anesthetic Using a
      Minimal Insertion Injection Technique.
AB  - BACKGROUND: The injection of local anesthetic into the skin is often the only
      memorable event described by the patient after dermatologic procedures.
      OBJECTIVE: The authors compared the pain felt during injection of local
      anesthetic using a minimal needle insertion technique with a 30- or 33-gauge
      needle. MATERIALS AND METHODS: Three hundred eighteen patients with tumors on the
      head and neck were injected with lidocaine using a previously described technique
      with either a 30- or 33-gauge needle. After injection, patients were surveyed
      using the visual assessment scale for pain. RESULTS: Seventy-seven percent of
      patients felt no pain with injection on the face using a 33-gauge needle compared
      with 64% with a 30 gauge, whereas 94% of patients felt no pain on the scalp with
      a 33-gauge needle compared with 54% with a 30 gauge. Visual analog scale scores
      were also significantly decreased on the face and scalp using the smaller needle.
      There was no difference in pain between the 2 needles with injection on the neck.
      CONCLUSION: This study further validates the use of this technique for the
      injection of lidocaine and the preference of a 33 gauge over a 30-gauge needle
      for the initial injection on the face and scalp.

PMID- 29016545
TI  - The Skin Surgery Patient Experience, a Retrospective Review.

PMID- 29016546
TI  - Histologic Accuracy of Mohs Micrographic Surgery.
AB  - BACKGROUND: Mohs micrographic surgery enables the surgeon to maximize tumor
      removal while minimizing the amount of tissue being removed using advanced
      mapping techniques combined with microscopy. Interpretation of frozen section
      slides is vital to the success of Mohs micrographic surgery. OBJECTIVE: Evaluate
      and confirm the congruence of frozen section slide interpretation between
      fellowship-trained Mohs surgeons and dermatopathologists. METHODS: Retrospective
      cohort concordance study spanning 10 years (n = 1,720 cases). RESULTS: The
      concordance rate for frozen slide interpretation between fellowship-trained Mohs
      surgeons and dermatopathologists in this study was 99.5%. CONCLUSION: This study
      demonstrates agreement between the interpretation of histologic frozen section
      slides when evaluated by fellowship-trained Mohs surgeons and
      dermatopathologists.

PMID- 29016547
TI  - A Cautionary Tale: A Vascular Event With Deoxycholic Acid Injection.

PMID- 29016548
TI  - Improving Sun-Protective Behaviors and Self-Skin Examinations Among African
      Americans: A Randomized Controlled Trial.
AB  - BACKGROUND: Few studies describing sun-protective behaviors, knowledge, and self
      efficacy in African Americans exist. Although educational programs targeting
      Caucasians and Hispanics have been successful in increasing melanoma awareness
      and knowledge, no such investigation has been applied to African Americans.
      OBJECTIVE: To evaluate the effectiveness of a brochure or video educational
      intervention on the sun-protective behaviors, knowledge, and self-efficacy
      regarding melanoma in African Americans. MATERIALS AND METHODS: A randomized
      controlled trial of a presurvey and postsurvey, in an academic outpatient
      dermatology clinic. Participants were self-identified African Americans, at least
      18 years old, fluent, and literate in English. Patients randomized to the
      brochure-intervention group (n = 72) received a melanoma brochure from the
      National Cancer Institute. Patients randomized to the video-intervention group (n
      = 71) received the brochure and watched an online melanoma tutorial. RESULTS: Sun
      protective behaviors, knowledge, and self-efficacy regarding melanoma all
      improved equally from pre-to posteducation, in both the brochure- and video
      intervention groups. CONCLUSION: Melanoma educational interventions similar to
      those previously demonstrated to be successful in Caucasian and Hispanic
      populations are also effective among African Americans.

PMID- 29016549
TI  - Depressive Symptoms, Antidepressant Medication Use, and Inflammatory Markers in
      the Diabetes Prevention Program.
AB  - OBJECTIVE: Antidepressant medication use (ADM) has been shown to predict
      diabetes. This article assessed the role of inflammatory markers in this
      relationship within the Diabetes Prevention Program (DPP). METHODS: DPP
      participants randomized to metformin (MET), life-style intervention (ILS), or
      placebo (PLB) were assessed for depression (Beck Depression Inventory [BDI])
      annually, ADM use semiannually, serum inflammatory markers (C-reactive protein
      [CRP], interleukin 6 [IL-6]) at baseline and year 1, and diagnosis of type 2
      diabetes mellitus (T2DM) semiannually (for 3.2 years). RESULTS: At baseline (N =
      3187), M (SD) body mass index was 34 (6) kg/m and the median (interquartile
      range) BDI score was 3 (1-7). One hundred eighty-one (5.7%) reported ADM use and
      328 (10%) had BDI scores of 11 or higher. CRP and IL-6 levels did not differ by
      treatment group. Baseline ADM, but not BDI score, was associated with higher
      levels of baseline CRP adjusted for demographic, anthropometric variables, and
      other medications (20% higher, p = .01). Year 1 CRP decreased for non-ADM users
      in the MET (-13.2%) and ILS (-34%) groups and ADM users in the ILS group (-29%).
      No associations were found with IL-6. CRP and continuous use of ADM predicted
      incident T2DM in the PLB group. In the ILS group, continuous and intermittent
      ADM, but not CRP, predicted T2DM. In the MET group, CRP predicted incident T2DM.
      CRP did not mediate the risk of T2DM with ADM use in any group. CONCLUSIONS: ADM
      was significantly associated with elevated CRP and incident T2DM. In the PLB
      group, ADM and CRP independently predicted onset of T2DM; however, CRP did not
      significantly mediate the effect of ADM.

PMID- 29016550
TI  - Assessing Lifetime Stress Exposure Using the Stress and Adversity Inventory for
      Adults (Adult STRAIN): An Overview and Initial Validation.
AB  - OBJECTIVE: Numerous theories have proposed that acute and chronic stressors may
      exert a cumulative effect on life-span health by causing biological "wear and
      tear," or allostatic load, which in turn promotes disease. Very few studies have
      directly tested such models, though, partly because of the challenges associated
      with efficiently assessing stress exposure over the entire life course. To
      address this issue, we developed the first online system for systematically
      assessing lifetime stress exposure, called the Stress and Adversity Inventory
      (STRAIN), and describe its initial validation here. METHODS: Adults recruited
      from the community (n = 205) were administered the STRAIN, Childhood Trauma
      Questionnaire-Short Form, and Perceived Stress Scale, as well as measures of
      socioeconomic status, personality, social desirability, negative affect, mental
      and physical health complaints, sleep quality, computer-assessed executive
      function, and doctor-diagnosed general health problems and autoimmune disorders.
      RESULTS: The STRAIN achieved high acceptability and was completed relatively
      quickly (mean = 18 minutes 39 seconds; interquartile range = 12-23 minutes). The
      structure of the lifetime stress data best fit two latent classes overall and
      five distinct trajectories over time. Concurrent associations with the Childhood
      Trauma Questionnaire-Short Form and Perceived Stress Scale were good (r values =
      .147-.552). Moreover, the STRAIN was not significantly related to personality
      traits or social desirability characteristics and, in adjusted analyses, emerged
      as the measure most strongly associated with all six of the health and cognitive
      outcomes assessed except current mental health complaints (beta values = .16-.41;
      risk ratios = 1.02-1.04). Finally, test-retest reliability for the main stress
      exposure indices over 2-4 weeks was excellent (r values = .904-.919).
      CONCLUSIONS: The STRAIN demonstrated good usability and acceptability; very good
      concurrent, discriminant, and predictive validity; and excellent test-retest
      reliability.

PMID- 29016551
TI  - Pectoral Fascial (PECS) I and II Blocks as Rescue Analgesia in a Patient
      Undergoing Minimally Invasive Cardiac Surgery.
AB  - INTRODUCTION: Patients undergoing minimally invasive cardiac surgery have the
      potential for significant pain from the thoracotomy site. We report the
      successful use of pectoral nerve block types I and II (Pecs I and II) as rescue
      analgesia in a patient undergoing minimally invasive mitral valve repair. CASE
      REPORT: In this case, a 78-year-old man, with no history of chronic pain,
      underwent mitral valve repair via right anterior thoracotomy for severe mitral
      regurgitation. After extubation, he complained of 10/10 pain at the incision site
      that was minimally responsive to intravenous opioids. He required supplemental
      oxygen because of poor pulmonary mechanics, with shallow breathing and splinting
      due to pain, and subsequent intensive care unit readmission. Ultrasound-guided
      Pecs I and II blocks were performed on the right side with 30 mL of 0.2%
      ropivacaine with 1:400,000 epinephrine. The blocks resulted in near-complete
      chest wall analgesia and improved pulmonary mechanics for approximately 24 hours.
      After the single-injection blocks regressed, a second set of blocks was performed
      with 266 mg of liposomal bupivacaine mixed with bupivacaine. This second set of
      blocks provided extended analgesia for an additional 48 hours. The patient was
      weaned rapidly from supplemental oxygen after the blocks because of improved
      analgesia. CONCLUSIONS: Pectoral nerve blocks have been described in the setting
      of breast surgery to provide chest wall analgesia. We report the first successful
      use of Pecs blocks to provide effective chest wall analgesia for a patient
      undergoing minimally invasive cardiac surgery with thoracotomy. We believe that
      these blocks may provide an important nonopioid option for the management of pain
      during recovery from minimally invasive cardiac surgery.

PMID- 29016552
TI  - The Efficacy of Peripheral Opioid Antagonists in Opioid-Induced Constipation and
      Postoperative Ileus: A Systematic Review of the Literature.
AB  - Opioid-induced constipation has a negative impact on quality of life for patients
      with chronic pain and can affect more than a third of patients. A related but
      separate entity is postoperative ileus, which is an abnormal pattern of
      gastrointestinal motility after surgery. Nonselective MU-opioid receptor
      antagonists reverse constipation and opioid-induced ileus but cross the blood
      brain barrier and may reverse analgesia. Peripherally acting MU-opioid receptor
      antagonists target the MU-opioid receptor without reversing analgesia. Three such
      agents are US Food and Drug Administration approved. We reviewed the literature
      for randomized controlled trials that studied the efficacy of alvimopan,
      methylnaltrexone, and naloxegol in treating either opioid-induced constipation or
      postoperative ileus. Peripherally acting MU-opioid receptor antagonists may be
      effective in treating both opioid-induced bowel dysfunction and postoperative
      ileus, but definitive conclusions are not possible because of study inconsistency
      and the relatively low quality of evidence. Comparisons of agents are difficult
      because of heterogeneous end points and no head-to-head studies.

PMID- 29016553
TI  - Bleeding and Neurologic Complications in 58,000 Interventional Pain Procedures.
AB  - BACKGROUND AND OBJECTIVES: Interventional pain procedures are commonly performed
      on patients receiving antiplatelet therapy. However, there is limited evidence to
      support or refute the safety of this practice. The goal of this investigation was
      to assess the rate of bleeding complications in a large cohort of patients
      undergoing intermediate- and low-risk pain procedures, with a specific focus on
      antiplatelet and anticoagulant medication use and baseline coagulation
      abnormalities. METHODS: This is a retrospective cohort study of adult patients
      undergoing low- and intermediate-risk pain procedures from 2005 through 2014 by
      the division of pain medicine at a single academic tertiary care center. Baseline
      characteristics, antiplatelet and anticoagulant medication use, coagulation
      parameters, and procedural details were extracted from the electronic medical
      record. The primary outcome was a bleeding-related complication requiring
      emergency medicine, neurology, or neurosurgical evaluation within 31 days. The
      secondary outcome was the presence or absence of a periprocedural red blood cell
      transfusion occurring within 72 hours of needle placement. RESULTS: A total of
      58,066 procedures were performed on 24,590 unique patients. Preprocedural aspirin
      or nonsteroidal anti-inflammatory drug therapy was present for 17,825 procedures
      (30.7%). Sixteen procedures were associated with perioperative red blood cell
      transfusion (0.03%), with no difference based on preprocedural nonsteroidal anti
      inflammatory drug, including aspirin, or other anticoagulation use (P = 0.107).
      Five patients (0.009%) had a neurologic complication requiring further
      evaluation, of which 2 were likely related to procedural bleeding. CONCLUSIONS:
      Bleeding complications are rare in patients undergoing low- or intermediate-risk
      pain procedures even in the presence of antiplatelet medications. This is
      consistent with recently released guidelines.

PMID- 29016554
TI  - A Modified Laminoplasty Technique to Treat Cervical Myelopathy Secondary to
      Ossification of the Posterior Longitudinal Ligament (OPLL).
AB  - BACKGROUND This study aimed to evaluate the validity of modified laminoplasty in
      treating close-base OPLL with an occupying ratio of more than 60%. MATERIAL AND
      METHODS Forty-seven close-base OPLL patients with an occupying ratio of more than
      60% were treated through modified laminoplasty (N=22) and combined anterior
      posterior approach (N=25) in the study, including 17 females and 30 males, with a
      mean age of 60.59+/-6.76 years (ranging from 46 to 75 years). The patients'
      characteristics, the recovery rate of neurological function, length of the
      operation, intraoperative blood loss, hospital costs, and complications were
      recorded and compared between the 2 groups. RESULTS The recovery rate of
      neurological function did not demonstrate a significant difference between the 2
      groups (P=0.886). However, length of the operation and intraoperative blood loss
      in the modified laminoplasty group were shorter than those in the combined
      anterior-posterior approach group (P=0.001 and P=0.023). Moreover, the mean
      hospital costs in the modified laminoplasty group (5166.61+/-123.27 USD)
      decreased by 33.6% compared with the combined anterior-posterior approach group
      (7780.12+/-256.73 USD). Additionally, the complications of the modified
      laminoplasty group were lower than in the combined anterior-posterior approach
      group. CONCLUSIONS Modified laminoplasty may be considered a safe and effective
      strategy for patients that have demonstrated close-base OPLL with an occupying
      ratio of more than 60% and who cannot endure the trauma caused by the combined
      anterior-posterior approach due to medical disease.

PMID- 29016555
TI  - Interleukin-10-regulated tumour tolerance in non-small cell lung cancer.
AB  - BACKGROUND: Lung cancer is the most life-threatening cancer type worldwide.
      Treatment options include surgery, radio- and chemotherapy, as well as the use of
      immunomodulatory antibodies. Interleukin (IL)-10 is an immunosuppressive cytokine
      involved in tumour immune escape. METHODS: Immunohistochemistry (IHC) on human
      lung surgery tissue as well as human tumour cell line cultures, FACS analysis,
      real-time PCR and experimental lung cancer. RESULTS: Here we discovered a
      positive correlation between IL-10 and IL-10 receptor (IL-10R) expression in the
      lung with tumour diameter in patients with lung cancer (non-small cell lung
      cancer), the most life-threatening cancer type worldwide. IL-10 and IL-10R were
      found induced in cells surrounding the lung tumour cells, and IL-10R was mainly
      expressed on the surface of Foxp-3+ T-regulatory lymphocytes infiltrating the
      tumour of these patients where its expression inversely correlated with
      programmed cell death 1. These findings were confirmed in translational studies.
      In a human lung adenocarcinoma cell line, IL-10R was found induced under
      metabolic restrictions present during tumour growth, whereby IL-10 inhibited PDL1
      and tumour cell apoptosis. CONCLUSIONS: These new findings suggest that IL-10
      counteracts IFN-gamma effects on PD1/PDL1 pathway, resulting in possible
      resistance of the tumour to anti-PD1/PDL1 immunotherapy.

PMID- 29016557
TI  - Future perspectives of cell therapy for neonatal hypoxic-ischemic encephalopathy.
AB  - Neonatal ischemic brain injury causes permanent motor-deficit cerebral palsy.
      Hypoxic-ischemic encephalopathy (HIE) is a very serious condition that can result
      in death and disability. In 1997, we reported that irreversible neuronal cell
      damage is induced by the elevation of intracellular Ca ion concentration that has
      occurred in sequence after excess accumulation of the excitatory neurotransmitter
      glutamate during ischemia. We also reported that hypothermia was effective in
      treating ischemic brain damage in rats by suppressing energy loss and raising
      intracellular Ca ion concentration. Following the 2010 revised International
      Liaison Committee on Resuscitation guideline, our group developed the Guideline
      for the treatment of Hypothermia in Japan, and we started online case registry in
      January 2012. However, therapeutic hypothermia must be initiated within the first
      6 h after birth. By contrast, cell therapy may have a much longer therapeutic
      time window because it might reduce apoptosis/oxidative stress and enhance the
      regenerative process. In 2014, we administered autologous umbilical cord blood
      stem cell (UCBC) therapy for neonatal HIE, for the first time in Japan. We
      enrolled five full-term newborns with moderate-to-severe HIE. Our autologous UCBC
      therapy is leading to new protocols for the prevention of ischemic brain damage.

PMID- 29016556
TI  - The current status and future of cardiac stem/progenitor cell therapy for
      congenital heart defects from diabetic pregnancy.
AB  - Pregestational maternal diabetes induces congenital heart defects (CHDs). Cardiac
      dysfunction after palliative surgical procedures contributes to the high
      mortality of CHD patients. Autologous or allogeneic stem cell therapies are
      effective for improving cardiac function in animal models and clinical trials. c
      kit+ cardiac progenitor cells (CPCs), the most recognized CPCs, have the
      following basic properties of stem cells: self-renewal, multicellular clone
      formation, and differentiation into multiple cardiac lineages. However, there is
      ongoing debate regarding whether c-kit+ CPCs can give rise to sufficient
      cardiomyocytes. A new hypothesis to address the beneficial effect of c-kit+ CPCs
      is that these cells stimulate endogenous cardiac cells through a paracrine
      function in producing a robust secretome and exosomes. The values of other
      cardiac CPCs, including Sca1+ CPCs and cardiosphere-derived cells, are beginning
      to be revealed. These cells may be better choices than c-kit+ CPCs for generating
      cardiomyocytes. Adult mesenchymal stem cells are considered immune-incompetent
      and effective for improving cardiac function. Autologous CPC therapy may be
      limited by the observation that maternal diabetes adversely affects the
      biological function of embryonic stem cells and CPCs. Future studies should focus
      on determining the mechanistic action of these cells, identifying new CPC
      markers, selecting highly effective CPCs, and engineering cell-free products.

PMID- 29016559
TI  - The Reflux Improvement and Monitoring (TRIM) Program Is Associated With Symptom
      Improvement and Weight Reduction for Patients With Obesity and Gastroesophageal
      Reflux Disease.
AB  - OBJECTIVES: Current healthcare systems do not effectively promote weight
      reduction in patients with obesity and gastroesophageal reflux disease (GERD).
      The Reflux Improvement and Monitoring (TRIM) program provides personalized,
      multidisciplinary, health education and monitoring over 6 months. In this study
      we aimed to (i) measure the effectiveness of TRIM on GERD symptoms, quality of
      life, and weight, and (ii) examine patient health beliefs related to TRIM.
      METHODS: This prospective mixed methods feasibility study was performed at a
      single center between September 2015 and February 2017, and included adult
      patients with GERD and a body mass index >=30 kg/m2. Quantitative analysis
      consisted of a pre- to post-intervention analysis of TRIM participants (+TRIM
      Cohort) and a multivariable longitudinal mixed model analysis of +TRIM vs.
      patients who declined TRIM (-TRIM Cohort). Primary outcomes were change in
      patient-reported GERD symptom severity (GerdQ) and quality of life (GerdQ-DI),
      and change in percent excess body weight (%EBW). Qualitative analysis was based
      on two focus groups of TRIM participants. RESULTS: Among the +TRIM cohort (n=52),
      mean baseline GerdQ scores (8.7+/-2.9) decreased at 3 months (7.5+/-2.2; P<0.01)
      and 6 months (7.4+/-1.9; P=0.02). Mean GerdQ-DI scores decreased, but did not
      reach statistical significance. Compared with the -TRIM cohort (n=89), reduction
      in %EBW was significantly greater at 3, 6, and 12 months among the +TRIM cohort
      (n=52). In qualitative analysis, patients unanimously appreciated the
      multidisciplinary approach and utilized weight loss effectively to improve GERD
      symptoms. CONCLUSIONS: In this mixed methods feasibility study, participation in
      TRIM was associated with symptom improvement, weight reduction, and patient
      engagement.

PMID- 29016561
TI  - Technical Advances in Per-Oral Endoscopic Myotomy (POEM).

PMID- 29016560
TI  - Abdominal Pain in the Roux-en-Y Gastric Bypass Patient.

PMID- 29016558
TI  - A Comparison of Fecal Immunochemical and High-Sensitivity Guaiac Tests for
      Colorectal Cancer Screening.
AB  - OBJECTIVES: Annual testing using either a high-sensitivity guaiac fecal occult
      blood test (HS-gFOBT) or a fecal immunochemical test (FIT) is recommended for
      screening average-risk people for colorectal cancer. We compared the performance
      characteristics of the HS-gFOBT Hemoccult II SENSA and two FITs (InSure FIT and
      OC FIT-CHEK) for detecting advanced colorectal neoplasia. METHODS: The study
      included 1,006 asymptomatic patients, aged 50-75 years, who were scheduled to
      receive a screening colonoscopy at gastroenterology practices in the Minneapolis
      and Indianapolis metropolitan areas. Each participant was asked to complete all
      three stool tests before their colonoscopy. Each test's performance
      characteristics were evaluated using the screening colonoscopic results as the
      reference standard. RESULTS: Sensitivity for detecting advanced colorectal
      neoplasia was highest for InSure FIT (26.3%, 95% confidence interval (CI) 15.9
      40.7), followed by OC FIT-CHEK (15.1%, 95% CI 6.7-26.1) and Hemoccult II SENSA
      (7.4%, 95% CI 1.9-17.0). InSure FIT was statistically significantly more
      sensitive than both OC FIT-CHEK (absolute difference in sensitivity=11.2%, 95% CI
      0.4-24.2) and Hemoccult II SENSA (difference in sensitivity=18.9%, 95% CI 10.2
      32.6). Specificities were relatively high for all tests (between 96.8% and
      98.6%). CONCLUSIONS: Our results suggest that some FITs are more sensitive than
      the HS-gFOBT Hemoccult II SENSA, but these results need to be confirmed in larger
      asymptomatic populations. Comparisons between the FITs examined in this study and
      other FITs are needed to determine the best tests for population screening.

PMID- 29016563
TI  - CON: Hepatocellular Carcinoma Surveillance: In Need of Higher-Quality Data.

PMID- 29016562
TI  - Determinants of the Association between Non-Cardiac Chest Pain and Reflux.
AB  - OBJECTIVES: Gastroesophageal reflux is considered to be the most common
      gastrointestinal cause of non-cardiac chest pain (NCCP). It remains unclear why
      some reflux episodes in the same patient cause chest pain while others do not. To
      understand more about the mechanisms by which reflux elicits chest pain, we aimed
      to identify factors which are important in triggering chest pain. METHODS: In
      this multicenter study, 120 patients with NCCP were analyzed using 24-h pH
      impedance monitoring. In the patients with a positive association between reflux
      and chest pain, the characteristics of the reflux episodes which were followed by
      a chest pain episode were compared with chest pain-free reflux episodes. RESULTS:
      Using 24-h pH-impedance monitoring, 40% of the NCCP patients were identified as
      having reflux as a possible cause of their chest pain. Reflux episodes that were
      associated with chest pain had a higher proximal extent (P=0.007), a higher
      volume clearance time (P=0.030), a higher 15-minute acid burden (P=0.041), were
      more often acidic (P=0.011), had a lower nadir pH (P=0.044), and had a longer
      acid duration time (P=0.027) than reflux episodes which were not followed by
      chest pain. Patients who experienced typical reflux symptoms were more likely to
      have reflux as the cause of their chest pain (52 vs. 31.4%, P=0.023).
      CONCLUSIONS: The presence of a larger volume of acid refluxate for a longer
      period of time appears to be an important determinant of perceiving a reflux
      episode as chest pain. 24-h pH-impedance monitoring is an important tool in
      identifying gastroesophageal reflux as a potential cause of symptoms in patients
      with NCCP.

PMID- 29016564
TI  - The Role of an IgA/IgG-Deamidated Gliadin Peptide Point-of-Care Test in
      Predicting Persistent Villous Atrophy in Patients With Celiac Disease on a Gluten
      Free Diet.
AB  - OBJECTIVES: Mucosal healing is important in celiac disease (CD) for the
      prevention of complications. However, obtaining duodenal biopsies is invasive,
      and there is currently no reliable surrogate marker for histological remission in
      clinical practice. We aimed to assess the role of a point-of-care test (POCT)
      based on IgA/IgG-deamidated gliadin peptide, in detecting persistent villous
      atrophy (VA) in CD. METHODS: We prospectively recruited patients with CD
      attending endoscopy for the assessment of histological remission. All patients
      had IgA-endomysial (EMA) antibodies, IgA-tissue transglutaminase (TTG)
      antibodies, and the POCT performed, and completed a validated dietary adherence
      questionnaire. A gastroscopy was performed in all patients, with four biopsies
      taken from the second part of the duodenum and one from the duodenal bulb. We
      compared the diagnostic performance of the surrogate markers against duodenal
      histology as the reference standard. RESULTS: A total of 217 patients with CD
      (70% female, age range 16-83 years, median age 53 years) on a gluten-free diet
      (median duration 6 years) were recruited from 2013 to 2017. Eighty-five (39.2%)
      patients had persistent VA. The sensitivities of the POCT, TTG, EMA, and the
      adherence score in detecting VA were 67.1%, 44.7%, 37.7%, and 24.7% respectively
      (P=0.0005). The combination of the POCT and adherence score only marginally
      increased the sensitivity to 70.6% (59.7-80.0%). CONCLUSIONS: The sensitivity of
      the POCT was higher than the other surrogate markers in predicting VA. A POCT may
      provide the additional advantage of an immediate objective assessment of mucosal
      healing at the time of an office-based follow-up consultation.

PMID- 29016565
TI  - Colonoscopy vs. Fecal Immunochemical Test in Reducing Mortality From Colorectal
      Cancer (CONFIRM): Rationale for Study Design.
AB  - RATIONALE: Colorectal cancer (CRC) is preventable through screening, with
      colonoscopy and fecal occult blood testing comprising the two most commonly used
      screening tests. Given the differences in complexity, risk, and cost, it is
      important to understand these tests' comparative effectiveness. STUDY DESIGN: The
      CONFIRM Study is a large, pragmatic, multicenter, randomized, parallel group
      trial to compare screening with colonoscopy vs. the annual fecal immunochemical
      test (FIT) in 50,000 average risk individuals. CONFIRM examines whether screening
      colonoscopy will be superior to a FIT-based screening program in the prevention
      of CRC mortality measured over 10 years. Eligible individuals 50-75 years of age
      and due for CRC screening are recruited from 46 Veterans Affairs (VA) medical
      centers. Participants are randomized to either colonoscopy or annual FIT. Results
      of colonoscopy are managed as per usual care and study participants are assessed
      for complications. Participants testing FIT positive are referred for
      colonoscopy. Participants are surveyed annually to determine if they have
      undergone colonoscopy or been diagnosed with CRC. The primary endpoint is CRC
      mortality. The secondary endpoints are (1) CRC incidence (2) complications of
      screening colonoscopy, and (3) the association between colonoscopists'
      characteristics and neoplasia detection, complications and post-colonoscopy CRC.
      CONFIRM leverages several key characteristics of the VA's integrated healthcare
      system, including a shared medical record with national databases, electronic CRC
      screening reminders, and a robust national research infrastructure with
      experience in conducting large-scale clinical trials. When completed, CONFIRM
      will be the largest intervention trial conducted within the VA
      (ClinicalTrials.gov identifier: NCT01239082).

PMID- 29016566
TI  - Demographics, Resource Utilization, and Outcomes of Elderly Patients With Chronic
      Liver Disease Receiving Hospice Care in the United States.
AB  - OBJECTIVES: Hospice offers non-curative symptomatic management to improve
      patients' quality of life, satisfaction, and resource utilization. Hospice
      enrollment among patients with chronic liver disease (CLD) is not well studied.
      The aim of tis tudy is to examine the characteristics of Medicare enrollees with
      CLD, who were discharged to hospice. METHODS: Medicare patients discharged to
      hospice between 2010 and 2014 were identified in Medicare Inpatient and Hospice
      Files. CLDs and other co-morbidities were identified by International
      Classification of Diseases-ninth revision codes. Generalized linear model was
      used to estimate regression coefficients with P-values. Logistic regression was
      used to calculate odds ratios and 95% confidence intervals. RESULTS: A total of
      2,179 CLD patients and 34,986 controls without CLD met the inclusion criteria.
      Non-alcoholic fatty liver disease, alcoholic liver disease, and hepatitis C virus
      (HCV) were the most frequent cause of CLD. CLD patients were younger (70 vs. 83
      years), more likely to be male (57.7 vs. 39.3%), had longer hospital stay (length
      of stay, LOS) (19.4 vs. 13.0 days), higher annual charges ($175,000 vs.
      $109,000), higher 30-day re-hospitalization rates (51.6 vs. 34.2%), and shorter
      hospice LOS (13.7 vs. 17.7 days) than controls (all P<0.001). Presence of HCV and
      congestive heart failure were the strongest contributors to increased total
      annual costs (34% and 31% higher, P<0.001), increased total annual LOS (26% and
      43% higher, P<0.001), and increased 30-day readmission risk (2.20 and 2.19 times,
      respectively). CONCLUSIONS: Patients with CLD have longer and costly
      hospitalizations before hospice enrollment as compared with patients without CLD.
      It was highly likely that these patients were enrolled relatively late, which
      could potentially lead to less benefit from hospice.

PMID- 29016567
TI  - Effects of Bezafibrate on Outcome and Pruritus in Primary Biliary Cholangitis
      With Suboptimal Ursodeoxycholic Acid Response.
AB  - OBJECTIVES: Adding fibrates improves liver biochemistries in patients with
      primary biliary cholangitis (PBC) and suboptimal response to ursodeoxycholic acid
      (UDCA). As there are no consistent data regarding the course and outcome, we have
      assessed the effects of the combined treatment with UDCA and bezafibrate on a
      long-term basis. METHODS: A total of 48 patients (45 female) with PBC treated
      with UDCA and alkaline phosphatase (ALP) above 1.5 times upper normal levels (*
      UNL) were treated with bezafibrate (400 mg/day) plus UDCA (13-16 mg/kg/day).
      Changes in clinical features, liver biochemistries, and prognosis after therapy
      were assessed, as well as pruritus, using a visual analog scale (43 patients) and
      the 5-D descriptive pruritus scale. RESULTS: After a median of 38 months, 26
      patients (54%) had normalized ALP. In these patients, jaundice, pruritus, and
      liver stiffness was lower, and age was higher than in patients who remained with
      elevated ALP. Biochemical improvement was less prominent in patients without ALP
      normalization. Five of these patients (23%) developed events of disease
      progression: 1 died, 3 were transplanted, and 1 developed hepatocellular
      carcinoma. Partial or complete itching relief was reported in all but one case
      with pruritus. Itching recurrence or worsening was observed after bezafibrate
      discontinuation. CONCLUSIONS: The long-term treatment with UDCA and bezafibrate
      results in excellent response, and is associated with a complete or partial
      itching relief. Incomplete ALP normalization was observed in patients with
      advanced disease who remained at risk for developing severe events. The combined
      treatment is mainly effective in patients with lower fibrosis and severity of
      cholestasis.

PMID- 29016568
TI  - Job postings for biopharmaceutical industry in medical journals is 45-fold
      greater for hematology oncology than medical specialties.

PMID- 29016569
TI  - Efficacy of pegaspargase, etoposide, methotrexate and dexamethasone in newly
      diagnosed advanced-stage extra-nodal natural killer/T-cell lymphoma with the
      analysis of the prognosis of whole blood EBV-DNA.

PMID- 29016572
TI  - Financial conflicts of interest among editorialists in high-impact journals.

PMID- 29016570
TI  - Blinatumomab-induced lineage switch of B-ALL with t(4:11)(q21;q23) KMT2A/AFF1
      into an aggressive AML: pre- and post-switch phenotypic, cytogenetic and
      molecular analysis.

PMID- 29016571
TI  - Prevalence and timing of TP53 mutations in del(17p) myeloma and effect on
      survival.

PMID- 29016573
TI  - Family Planning 2020 and Nepal's Pledge.
AB  - NA.

PMID- 29016574
TI  - Microvascular Free Flaps in Oral and Maxillofacial Reconstruction following
      Cancer Ablation.
AB  - Microsurgical free flaps have become the first choice for reconstruction of oral
      and maxillofacial (OMF) defects after tumor resection. Till recently the
      pectoralis major myocutaneous flap (PMMC) was considered to be the benchmark for
      OMF reconstruction. This philosophy is changing fast with rapid advancement in
      reconstructive microsurgery. Years of innovation in reconstructive microsurgery
      has given us a reasonably good number of excellent flaps. Tremendous work has
      been put into producing some exceptionally brilliant research articles, sometimes
      contradicting each other. This has led to the need for clarity in some areas in
      this field. This article reviews the most common microvascular free flaps (MFF)
      namely, radial forearm free flap (RFFF), anterolateral thigh flap (ALT) and free
      fibula flap (FFF) that are commonly used in OMF reconstruction. Since they can
      cater to almost all sizeable defects we come across after ablative surgery in the
      OMF region, they can aptly be titled as the workhorses of OMF reconstruction with
      regard to free flaps.   Key words: Free tissue flaps, oral surgical procedures,
      microsurgery.

PMID- 29016575
TI  - Role of Intravenous Ferric Carboxy-maltose in Pregnant Women with Iron Deficiency
      Anaemia.
AB  - BACKGROUND: Iron deficiency is a common nutritional deficiency amongst women of
      childbearing age. Peri-partum iron deficiency anaemia is associated with
      significant maternal, foetal and infant morbidity. Current options for treatment
      include oral iron, which can be ineffective and poorly tolerated, and red blood
      cell transfusions, which carry an inherent risk and should be avoided. Ferric
      carboxymaltose is a modern treatment option. The study was designed to assess the
      safety and efficacy of intravenous ferric carboxymaltose for correction of iron
      deficiency anaemia in pregnant women. METHODS: A prospective study was conducted
      at Institute of Kidney Disease and Research Centre, Ahmedabad from January 2014
      to December 2016. Antenatal women (108) with iron deficiency anaemia were the
      study subjects. Socio-demographic profile was recorded and anaemia was assessed
      based on recent haemoglobin reports. Iron deficiency was diagnosed on basis of
      serum ferritin value. Intravenous ferric carboxymaltose as per total correction
      dose (maximum 1500mg) was administered to all women; the improvement in
      haemoglobin levels were assessed after 3 weeks of total dose infusion. RESULTS:
      Most of the women(n= 45, 41.7%), were in the age group of 27-30 years. Most of
      the women (n = 64, 59.3%) had moderate anaemia as per WHO guidelines. Mean
      haemoglobin levels significantly increased over a period of 3 weeks after Ferric
      carboxymaltose administrationand no serious life threatening adverse events were
      observed. CONCLUSIONS: Intravenous ferric carboxymaltose was safe and effective
      in pregnent women with iron deficiency anaemia.

PMID- 29016576
TI  - Quality of Clinical Notes: Lesson Learned from Elective Surgery Patients Admitted
      at University Teaching Hospital.
AB  - BACKGROUND: Informative relevant documentation regarding course of treatment
      minimizes errors, provides data for evidence based practice and legality.
      However, the clinical notes are often inadequate. This study aims to analyse
      quality of structured clinical notes in surgical patients. METHODS: This cross
      sectional study from Oct 1, 2015 in department of surgery included 100 clinical
      notes randomly selected by lottery. The entries in notes were predefined. There
      were 29 general entries (nine for identification, eleven for admission details,
      eight for treatment progress, and one for handwriting). Three additional entries
      were for discharge patients. The decision for entries was based on consensus
      meeting in surgery department. Microsoft excel was used for data entry and
      descriptive analysis. RESULTS: There were 100 clinical notes analysed, 62 non
      discharge and 38 discharge patients. Four (out of 62) non-discharge had all 29
      entries documented. Two (out of 38) in discharge had all 32 entries documented.
      The "date of entries, clinician name and designation" were mentioned in 12%, 13%
      and 10%, respectively. The progress on diet was recorded in 53%, investigations
      in 72% and intervention details in 73%. Handwriting was difficult to read in 21%.
      In 13 (out of 100) the identification information was incomplete. Discharge
      lacked details of home advice in 11%. CONCLUSIONS: The quality of clinical note
      of elective surgery patients needs improvement on documentation in all domains of
      identification, admission, progress and discharge.

PMID- 29016577
TI  - Can a Leaflet with Brief Verbal Instruction Teach Nepali Women How to Correctly
      Contract Their Pelvic Floor Muscles?
AB  - BACKGROUND: Pelvic organ prolapse is a common disorder for women in Nepal causing
      symptoms and reduced quality of life. Pelvic floor muscle exercise is a
      conservative treatment option for pelvic organ prolapse but the effective way to
      teach women in Nepal is not known. The objective of this pilot study was to
      determine if an illustrative leaflet with brief verbal instruction could teach
      Nepali women to correctly contract their pelvic floor muscles. METHODS: Fifteen
      parous women attending two outpatient gynecology clinics in Kathmandu Valley were
      interviewed to assess their knowledge of pelvic organ prolapse and pelvic floor
      muscles exercise. Following verbal instruction and an illustrative leaflet on how
      to contract their pelvic floor muscles, the transabdominal real time ultrasound
      was applied to assess the muscle contraction. RESULTS: The median age of 15
      participants was 45 years (range 18-75 years) and 10 women had pelvic organ
      prolapse. Some of the participants (9/15) knew about pelvic organ prolapse but
      none were aware of the pelvic floor muscles. After being taught how to contract
      their pelvic floor muscle, only 4 of 14 correctly contracted the pelvic floor
      muscle. CONCLUSIONS: This study highlighted the low knowledge of the pelvic floor
      muscle, and brief verbal instruction with an illustrative leaflet is also not
      sufficient in teaching Nepali women how to correctly contract their pelvic floor
      muscle. Further research is needed to determine how to teach a correct pelvic
      floor muscle contraction for women with low literacy in resource poor settings.

PMID- 29016578
TI  - Profile of Caesarean Section at Kathmandu Medical College.
AB  - BACKGROUND: There is a world-wide rise in caesarean section rateduring the last
      three decades and has been a cause of alarm and needs an in-depth study. The
      objective of this study was to determine the rate and clinical indications of
      Caesarean Section. METHODS: A hospital based study was carried out from 15th June
      2015 to 15th January 2016 in Department of Obstetrics and Gynecology at Kathmandu
      Medical College, Sinamangal, Nepal. Patients who delivered by caesarean section
      were included in the study. Basic demographic data and clinical indications were
      noted.?? Results: A total of 1172 deliveries were carried out during the study
      period. Total number of caesarean section was 537 accounting to 45.81%. Most of
      the patients were of the age group of 25-29 years (42.8%). Most of the patients
      were primigravida (n=274; 51%). Emergency caesarean section was 411 (76.5%) and
      elective caesarean section was 126 (23.4%). Multigravida (71%) underwent more
      elective procedure than primigravida (25. 39%).The most frequent indication was
      fetal distress19.55% (n=105), failed induction 19.73%(n=106), and previous
      caesarean section 21.3% (n=115). CONCLUSIONS: The rate of cesarean section is
      quite high than that recommended by WHO which is (10-15%). Most of the caesarean
      sections were emergency caesarean section with previous caesarean being the
      leading cause.

PMID- 29016579
TI  - Iodine and Thyroid Function Status, and Anti-thyroid Peroxidase Antibody among
      Pregnant Women in Eastern Nepal.
AB  - BACKGROUND: Iodine deficiency, thyroid dysfunction and development of thyroid
      autoimmunity during pregnancy may affect mother and the developing fetus. This
      study was carried out to find iodine status, thyroid dysfunction and thyroid
      autoimmunity among pregnant women. METHODS: Ninety two pregnant women from three
      districts of eastern Nepal (Sunsari, Morang and Jhapa) were enrolled for the
      study, and urine and blood samples were collected. Urinary iodine concentration
      (UIC), free thyroxine (free T4), thyroid stimulating hormone (TSH), thyroglobulin
      and anti-thyroid peroxidase (TPO) antibody levels were estimated. RESULTS: The
      median UIC, mean free T4 and TSH, median thyroglobulin and anti-TPO antibody in
      the pregnant women were 282.2 (158.42-376) MUg/L, 1.14+/-0.41 ng/dL, 4.57+/-2.56
      IU/mL, 6.5 (4.0-11.0) ng/mL, 1.52 (0.97-2.23) IU/mL respectively. In sufficient
      (<150 MUg/L), adequate (150-249 MUg/L) and above requirements (250-499 MUg/L)
      iodine intake was observed in 17 (18.5%), 22 (23.9%) and 53 (57.6%) women
      respectively. Subclinical hypothyroidism and overt hypothyroidism were seen in 18
      (19.5%) and 1(1.1%) women, respectively. Elevated thyroglobulin (>40 ng/mL) and
      positive anti-TPO antibody was observed in three (3.26%) women for both.
      CONCLUSIONS: Iodine intake was sufficient among pregnant women recently, however,
      chronic iodine deficiency persisted in small fraction of pregnant women. Mild
      thyroid dysfunction was common, and thyroid autoimmunity was present in small
      portion of Nepalese pregnant women population.

PMID- 29016580
TI  - Surgical Site Infections and Antimicrobial Resistance Pattern.
AB  - BACKGROUND: Post-operative surgical site infections (SSIs) are among the leading
      cause of morbidity and increased medical expense. The aim of this study is to
      isolate identify and study antimicrobial susceptibility pattern of microorganism
      from surgical wound of admitted patients. METHODS: This retrospective study was
      carried at the Microbiology Laboratory of Bharatpur hospital, Nepal, from May
      2015 to October 2015. The pus samples were cultured and antibiotic susceptibility
      determined in vitro by Kirby Bauer's disc diffusion method following clinical and
      Laboratory Standards Institute (CLSI) 2014 recommendation. RESULTS: Of the total
      250 samples, 194 (77.6%) showed bacterial growth. Staphylococcus aureus was 47.4%
      and Escherichia coli 20.60 %. Of 194 isolates 39.2% were multi drug resistant.
      Amikacin was sensitive in 93.1% of Gram positive isolates and 81.8% of gram
      negative isolates. CONCLUSIONS: Bacterial growth is common in surgical site.
      Staphylococcus aureus and Escherichia coli were multidrug resistant. Grampositive
      and gram negative isolates were commonly sensitive to Amikacin.

PMID- 29016581
TI  - Bacteriological Study of Otitis Media and Its Antibiotic Susceptibility Pattern.
AB  - BACKGROUND: Otitis Media is a prevailing and notorious infection in developing
      countries causing serious local damage and threating complication. Mainly in
      developing countries like Nepal, Otitis Media results because of illiteracy,
      poverty and poor hygiene. The aim of this study was to determine the profile of
      Otitis Media, its causative agents and their antibiotic susceptibility pattern.
      METHODS: The study included 263 pus samples from 240 patients attending ENT
      department of Bharatpur hospital from May 2015 to January 2016. Samples were
      processed in microbiology department for bacteria using standard operating
      protocol. Antibiotic susceptibility testing was performed for all bacterial
      isolates by Kirby Bauer disc diffusion method and the results were interpreted
      according to clinical and laboratory standard institute (CLSI) guideline.
      RESULTS: Out of 240 patients, 121 were female and 119 were male. Highest
      incidence of Otitis Media was observed in 1-10 year age group. Out of 263 samples
      taken from 240 patients, 216 showed bacterial growth. Gram negative bacteria
      predominated and the most common bacteria isolated were Staphylococcus aureus
      36.11% followed by Pseudomonas aeruginosa 33.33% and Coagulase Negative
      Staphylococci 8.08%. All bacterial isolates were sensitive to gentamycin.
      Staphylococcus aureus was sensitive to Amikacin and gentamycin. All gram negative
      bacterial isolates were sensitive to Imipenem and gentamycin. 100% of Pseudomonas
      aeruginosa was sensitive to Imipenem. CONCLUSIONS: Staphylococcus aureus was the
      most predominant organism isolated from the pus swab followed by Pseudomonas
      aeruginosa and all the isolated organisms were sensitive to Gentamycin.

PMID- 29016582
TI  - Safety and Efficacy of Percutaneous Nephrolithotomy in Children.
AB  - BACKGROUND: Renal stone disease is a common problem in children in developing
      countries. Its prevalence in children varies from 5% to 15%. It is suggested that
      anatomic abnormalities, recurrent urinary tract infections, metabolic
      disturbances, dietary and environmental factors are the predisposing factors.The
      aim of this study is to evaluate the safety and efficacy of percutaneous
      nephrolithotomy in children. METHODS: Between May 2012 and Dec 2016, 25 children
      with renal stone diseases underwent percutaneous nephrolithotomy and were
      evaluated for stone free rate, complications, blood transfusion rate, sandwich
      therapy, etc. RESULTS: The mean age of children was 9.3 years (7-15 years) and
      the mean size of the stone was 20 mm (13-27 mm). The anatomical location of stone
      was important in terms of stone clearance. Three patients needed blood
      transfusion. The overall stone free rate was 88% before discharge. Three patients
      had residual stones and were treated with extracorporeal shockwave lithotripsy.
      Complications included fever, haematuria, ileus and urine leak. No major
      complications were noted. There were no significant differences in haemoglobin
      and creatinine levels before and 12 hours after the surgery. CONCLUSIONS:
      Percutaneous nephrolithotomy (PCNL) can be considered a safe, effective and
      feasible modality of treatment for children with an average of 2 cm sized renal
      stones.

PMID- 29016583
TI  - Transabdominal Pre-peritoneal Mesh Repair versus Lichtenstein's Hernioplasty.
AB  - BACKGROUND: In the era of minimal invasive surgery, hernia repair has seen a
      paradigm shift from open to laparoscopic technique. However, superiority of
      laparoscopic repair over open repair is still controversial. Available
      literatures have shown laparoscopic technique to be better in term of post
      operative pain and early return to work. METHODS: In this prospective study, a
      total of 102 patients aged 21-78 years with inguinal hernia were recruited and
      enrolled into two comparative groups, namely Lichtenstein's and Transabdominal
      pre-peritoneal, and each group containing 51 participants. Hospital ethical
      committee approval and written informed consent from patients was obtained.
      Primarily, the duration of operation, post-operative pain and complication, and
      quality of life after surgery was compared between the two different approaches
      of hernia repair. RESULTS: The study results demonstrated a statistically
      significant superiority of trans abdominal pre-peritoneal repair over
      Lichtenstein's hernioplasty in terms of post operative pain (2.00+/-0.63 vs
      3.90+/-0.74 VAS score, P value<0.001), hospital stay (2.33+/-0.62 vs 2.96+/-0.20
      days, P value <0.001) and quality of life with early return to normal work
      (13.39+/-0.60 vs 17.88+/-0.86 days, P value <0.001); whereas a prolonged
      operative time was seen in transabdominal pre-peritoneal repair (96.08+/-27.08 vs
      42.55+/-5.95 mins, P value <0.001). CONCLUSIONS: This study has shown that
      transabdominal pre-peritoneal repair is better than Lichtenstein's in respect to
      post-operative pain, quality of life and post-operative complication. However, it
      has prolonged operative duration than conventional method.

PMID- 29016584
TI  - Morbidities and Outcome of a Neonatal Intensive Care in Western Nepal.
AB  - BACKGROUND: Neonatal mortality rate of developing countries is declining over
      decades. In the recent years increasing number of preterm and high risk neonates
      have facilities for tertiary care treatment. The aim of the study was to assess
      the morbidities and outcome of neonatal intensive care admissions. METHODS: It
      was a retrospective observational study carried out in neonatal intensive care
      unit of the Manipal Teaching Hospital, Pokhara, Nepal from January 2014 to
      December 2015. Neonatal details including place of delivery, birth weight,
      gestation, diagnosis at admission, hospital course and final outcome were
      recorded in predesigned proforma. Risk of mortality was calculated using odds
      ratio and 95% confidence interval. RESULTS: There were total 1708 admission
      during study period and inborn as well as out born neonates were equally
      admitted. Neonatal hyperbilirubinemia (37.1%), neonatal sepsis 532 (31.2%),
      prematurity, 314 (18.4%) perinatal asphyxia 112 (6.6%), meconium aspiration
      syndrome 79 (4.6%) and intrauterine growth restriction 49 (2.8%) were main
      indications for hospitalization. A total of 1410 (82.6%) the patients were
      discharged after treatment, 167 (9.7) left against medical advice, 115 (6.7%)
      died in hospital and 16 (1%) cases were referred. Preterm neonates had twice the
      risk of mortality than term neonates (OR =2.1664). Birth weight < 2500 grams had
      three times more risk of neonatal mortality than normal birth weight (OR
      =3.0783). CONCLUSIONS: Neonatal hyperbilirubinemia, prematurity and neonatal
      sepsis were common morbidities inneonatal intensive care unit.

PMID- 29016585
TI  - Isolation of Multidrug Resistant Bacteria from Patients Medical Charts.
AB  - BACKGROUND: Patient's medical charts in hospitals are potentially contaminated by
      pathogenic bacteria and might act as vehicles for transmission of bacterial
      infections.This study was aimed to determine the rate of contamination of medical
      charts by multidrug resistant bacteria. METHODS: Sampling of total 250 patient's
      medical charts from different wards was done with the help of cotton swabs soaked
      in sterile normal saline. The swabs thus collected were cultured using standard
      microbiological procedures.The colonies grown were then identified with the help
      of colony morphology, Gram's stain and biochemical tests. Antimicrobial
      susceptibility testing was performed by using Kirby-Bauer disc diffusion
      technique. RESULTS: Of the total 250 charts sampled, 98.8% grew bacteria;
      Bacillus spp. in 40.7%, followed by Staphylococcus aureus (17%), coagulase
      negative Staphylococcus spp.(CoNS) (17%), Citrobacter freundii (9.6%) and
      Acinetobacter spp. (4.5%). Rate of multidrug resistance was highest in
      Acinetobacter spp. (50%). Among 83 isolates of S. aureus, methicillin resistance
      was found in 29 isolates. Similarly, two out of total 9 isolates of Enterococcus
      spp. were vancomycin resistant. CONCLUSIONS: This study showed that patient's
      medical charts were contaminated with multidrug resistant bacteria including
      methicillin resistant S. aureus and vancomycin resistant Enterococcus spp. Strict
      hand washing before and after handling medical charts is recommended.

PMID- 29016587
TI  - Bogota Bag in Abdominal Compartment Syndrome at Kathmandu Model Hospital.
AB  - BACKGROUND: The gold standard of quick and definitive treatment of Abdominal
      compartment syndrome (ACS) is surgical decompression by opening the abdomen and
      leaving it open until intra-abdominal pressure decreases. Temporary abdominal
      closure techniques are used to postpone definite closure until predisposing
      factors causing pathologic elevation of intra-abdominal pressure are
      resolved.This study aim to analyze feasibility of Bogota Bag placement as a way
      of temporary abdominal closure. METHODS: Cases admitted in the period of eight
      years that were diagnosed to have or at risk to develop ACS and managed with
      'Bogota Bag', irrespective of primary diagnosis were reviewed retrospectively.
      Cause of ACS, reasons to place Bogota bag, its complications and final outcome in
      terms of mortality related or not related with Bogota Bag placement were
      assessed. RESULTS: Total of ten patients had placement of Bogota Bag in the
      period of eight years. Laparotomy for bowel perforation with peritonitis was the
      most common primary condition contributing to ACS. Bogota bag was placed in two
      cases after emergency decompression as a therapeutic measure whereas others were
      done as prophylactic measure. There were two mortalities (20%) which were not
      directly related to abdominal compartment syndrome. CONCLUSIONS: Abdomen closure
      with Bogota Bag for patients with ACS or likely to develop ACS is a feasible
      technique with minimal procedure related morbidities.

PMID- 29016586
TI  - Preference of Food-items and Physical Activity of Peri-urban Children in
      Bhaktapur.
AB  - BACKGROUND: Though cardiovascular diseases are mostly seen in adulthood, the
      foundation of diet and physical activity is largely formed during childhood. The
      study aimed to explore children's preference for diet and physical activity in a
      peri-urban area of Nepal because this is an important dimension to explore in the
      life-course approach to combat non-communicable diseases. METHODS: We conducted a
      cross-sectional study to enquire young peri-urban children of Duwakot and
      Jhaukhel villages of Bhaktapur district, Nepal on their preferences for diet and
      physical activity. All eligible households with children in the age range 5-10
      years as enlisted from the Jhaukhel-Duwakot Health Demographic Surveillance Site
      database were selected for the study. Twelve enumerators visited the selected
      households and facilitated the eligible children to fill in the questionnaire. We
      used a child-friendly photo-assisted questionnaire with face-scales that easily
      enabled the children to select a particular preference for each of the food item
      and physical activity. During analysis, food items were categorized into 'green',
      'yellow' and 'red' on the basis of their nutritive values. Physical activity was
      categorized based on severity of the activity. RESULTS: Four hundred and thirty
      seven children filled up the questionnaires. Overall, median preference scores
      for 'red' food were higher than for healthier 'green' food (4.16 vs. 4.03),
      particularly, if mothers were self-employed. Likewise, the children preferred low
      over moderate-to-severe physical activity (4.16 vs. 3.50), and preference was
      affected by parents' occupation and income. CONCLUSIONS: The study objectively
      revealed that most of the children preferred unhealthier food-items and low
      physical activities. It shall be useful to consider these findings while planning
      health promotional activities targeted at them.

PMID- 29016588
TI  - Mesiodens: A Hospital Based Study.
AB  - :  Background: A mesiodens, is the most frequent supernumerary tooth present in
      the maxillary central incisor region. This study is conducted to know the
      radiographic characteristics and management of mesiodens in children visiting
      hospital. METHODS: A cross-sectional retrospective data collection was done from
      hospital dental records of children who visited the institution from December
      2015-December 2016. Radiographic characteristic of mesiodens including the
      number, shape, position, direction of crown and complication caused by mesiodens
      were recorded. Data were analyzed using IBM SPSS v.20.0. RESULTS: Out of 1871
      dental records, it was found that 40 children had 53 mesiodens, with male female
      ratio of 3:1 and most of them were discovered at 8 years. Majority of mesiodens,
      54.7% were erupted, conical, palatally placed with 77.3% vertically directed
      crown.Complications associated with it were crowding followed by diastema and
      delayed eruption. Among 40 children, one had three mesiodens, eleven had two
      mesiodens and rest had one each. Radiographically fully formed tooth was seen in
      29 mesiodens. Immature apex was seen in 38 central incisors associated with
      mesiodens. Management undertaken was simple/surgical extraction and only few
      cases were kept for periodic observation. CONCLUSIONS: Periodic radiographs act
      as an important tool for clinicians in detecting and managing mesiodens.

PMID- 29016589
TI  - Risk Factors Associated with Low Birth Weight among Deliveries at Bharatpur
      Hospital.
AB  - BACKGROUND: Babies with a birth weight of less than 2500 grams, irrespective of
      the period of their gestation are termed as Low Birth Weight (LBW) babies.
      Despite consistent efforts to improve the quality of maternal and child health,
      more than twenty million low birth-weight (LBW) babies are born every year
      throughout the world. Though, the health situation of Nepal has improved
      substantially over the years, the low birth-weight (LBW) rate is still high. The
      objective of this study was to assess the proportion of low birth weight and
      identify the associated factors for low birth weight in a live born infant among
      the institutionally delivered newborns. METHODS: A hospital based cross sectional
      study was conducted in Obstetrics and Gynaecology ward of Bharatpur hospital,
      Bharatpur, from 17th September to 4th October , 2012. Altogether 480 respondents
      were taken and respondents were mothers who had delivered newborns in Bharatpur
      hospital. RESULTS: A total of 480 births occurred during the study period, of
      which 480 met the study criteria. Among which 9.4% were low birth weight and
      90.6% were normal birth weight .Overall mean birth weight was found to be 2.96
      kg. Out of total 9.4% newborns were weighing less than 2.50 kg and mean birth
      weight 2.96kg. CONCLUSIONS: This study suggests that there were several factors
      interplaying which lead to LBW babies; which are age of mother at delivery,weight
      gain by mother during pregnancy, short, low body mass index and hyperemesis
      gravidarum was the strongest predictor in this study.

PMID- 29016590
TI  - Endoscopic Endonasal Transsphenoidal Approach to Pituitary Adenoma: A Multi
      disciplinary Approach.
AB  - BACKGROUND: The excellent visualization and minimally invasive approach employed
      in endoscopic endonasal procedures has now revolutionized the pituitary surgery,
      replacing the transnasal microscopic technique worldwide. However, it involves
      major shift in hand-eye co-ordination from static 3 dimensional images of
      microscope to 2 dimensional endoscopic images hence demands training and inter
      disciplinary approach. Here we present our experiences in learning and developing
      a safe endonasal transsphenoidal endoscopic approach to resect pituitary
      adenomas. METHODS: This prospective study was jointly conducted in the
      departments of ENT and Neurologicals surgery Kathmandu Medical College, Nepal,
      from September 2014 to August 2016. The endoscopic approach to the sphenoid sinus
      was performed by an Otolaryngologist and ablative surgery by Neurosurgeon. The
      ease of procedure, intra operative challenges, surgical cure, post-operative
      cerebro spinal fluid (CSF) leaks and postoperative complaints were analyzed.
      RESULTS: Sixteen consecutive patients with pituitary adenoma (macro adenoma=13,
      micro adenoma =3) were analyzed. There were three intraoperative CSF leak,
      managed successfully. Two patients developed transient diabetes insipidus and
      surgical cure rate was 90%. No case had to be switched over to traditional
      microscopic route due to technical failure. There was no mortality. CONCLUSIONS:
      The endoscopic endonasal transsphenoidal approach to pituitary tumors is a safe
      and minimally invasive procedure, which can be employed safely in any of our
      centers in Nepal, equipped with endoscopic sinus surgery and endoscopically
      trained ENT and Neurosurgeons. A multi disciplinary approach provides good
      access, greater tumor excision and excellent postoperative follow up.

PMID- 29016591
TI  - Caesarean Section During Second Stage of Labor in a Tertiary Centre.
AB  - BACKGROUND: There is an alarming rise in caesarean section leading to increased
      adverse outcomes for both the mother and fetus when compared with vaginal
      delivery. Within this increasing caesarean section rate, there is a concerning
      increase in the rate of second stage caesarean section. This study highlight the
      feto-maternal outcome of caesarean section in second stage of labour. METHODS:
      This was a retrospective cohort review of all women with a singleton, cephalic
      fetus at term delivered by caesarean section in the second stage of labor between
      April 1, 2013 and March 30, 2017 at Patan Academy of Health Sciences. The main
      outcome measures were second stage caesarean section, indications and its
      maternal and fetal morbidity. RESULTS: During the study period, there were 40,860
      deliveries. A total of 18,011 (44%) babies were born by caesarean section, 10484
      emergency and 7527 elective. Out of the emergency caesarean section, 200 (1.9 %)
      were performed in second stage of labor. In this study, the most common
      indication was cephalopelvic disproportion. (92.4%) were delivered without a
      trial of instrumental delivery. In terms of maternal complications, atonic post
      partum haemorrhage uterine incision extension 18 (12.5%), postoperative fever
      27(18.8%), wound infection 7 (4.8%) were observed. In perinatal complications,
      meconium stained amniotic fluid 49(34.2%), neonatal hyperbilirubinemia 14(9.7%)
      and increased nursery admission 2(15.3%) and 2(1.3%) perinatal mortality were
      seen. CONCLUSIONS: Cesarean sections done in second stage of labor are associated
      with several intra-operative maternal complications and neonatal morbidity.

PMID- 29016592
TI  - Availability of Life Support Equipment and its Utilization by Ambulance Drivers.
AB  - BACKGROUND: An effective ambulance is a vital requirement for providing an
      emergency medical service. Well-equipped ambulances with trained paramedics can
      save many lives during the golden hours of trauma care. The objective was to
      document the availability and utilization of basic life support equipment in the
      ambulances and to assess knowledge on first aid among the drivers. METHODS:
      Descriptive design was used. Total of 109 ambulances linked to B.P. Koirala
      Institute of Health Sciences were enrolled using purposive sampling method. Self-
      constructed observation checklist and semi structured interview schedule was used
      for data collection. RESULTS: More than half of the respondents had less than
      five years of experience and were not trained in first aid. About two-third of
      the respondents had adequate knowledge on first aid. About 90% of the ambulance
      had oxygen cylinder and adult oxygen mask which was 'usually' used equipment.
      More than half of ambulance had equipment less than 23% as compared to that of
      national guidelines. There was significant association of knowledge with the
      experience (p = 0.004) and training (p = 0.001). Availability of equipment was
      associated with training received (p = 0.007),organization (p= 0.032)and district
      (p = 0.023) in which the ambulance is registered. CONCLUSIONS: The study
      concludes that maximum ambulance linked to BPKIHS, Nepal did not have even one
      fourth of the equipment for basic life support. Equipment usually used was oxygen
      cylinder and oxygen mask. Majority of driver had adequate knowledge on first aid
      and it was associated with training and experience.

PMID- 29016593
TI  - Dentists in Nepal: A Situation Analysis.
AB  - BACKGROUND: Human resource data is essential for planning and implementation of
      health care delivery system. However, very few information is available on dental
      health human resource in the country. The aim of study was to assess the number
      of dentists in the country and to explore their distribution according to
      demographic and professional characteristics. METHODS: A census was performed
      during July 2015 to July 2016 about the Nepali dentists. The study assessed
      demographic and professional characteristics of dentists including age, gender,
      ethnicity, education attainment, university, country/year of graduation, and work
      place using data collection sheet by trained data collectors. For those not
      accessible for direct contact, the information was obtained through secondary
      data. Data entry was done in CSPro software application and was analyzed in SPSS
      20. RESULTS: The total number of registered Nepali dentists was 1803 with 419
      specialists until June 2015. The male to female ratio was 1:1.46. Among all; 1318
      (73%) were present in the country, 1047 (58%) were professionally active, and
      1366 (76%) were below the age of 35 years. Among the professionals; 831 (79%)
      were employed in private sector and 601 (57%) worked in Kathmandu valley.
      CONCLUSIONS: The dentist-population ratio is decreasing exponentially in capital
      and major cities of Nepal however it remains very high in rural areas. Compared
      to other provinces,Province 6 and Province 7 lack service of dentists.

PMID- 29016594
TI  - Application of Ultraviolet Light in Dental Identification of Avalanche Victims.
AB  - In any disaster, it becomes important to identify the deceased for ethical,
      social and legal causes.Out of the numerous methods of identification, dental
      comparison is considered to be one of the scientific methods in a Disaster Victim
      Identification process. The two victims of avalanche in Nepal were identified
      using dental comparison. The two bodies brought for examination were
      unidentifiable visually. To aid identification of tooth coloured restorations,
      ultraviolet light was used. The ultraviolet light made the tooth coloured
      restorations appear distinct from the adjacent tooth structure in one of the
      cases. This helped in post-mortem charting of dental examination with greater
      accuracy. When the ante-mortem dental records and the post-mortem dental findings
      were compared, positive identification was made for both the cases. The bodies
      were then handed over to their respective kin. These cases highlighted the
      importance of ultraviolet light in post-mortem dental examination and the
      significance of forensic dentistry in identification process.

PMID- 29016595
TI  - Reporting of Medical Errors in Autopsied Cases.
AB  - This report describes the cases autopsied at B. P. Koirala Institute of Health
      Sciences- Nepal, during the period of two years in which the treatment provided
      falls below the accepted standard practice causing the death of the patient.
      Postmortem examination provides an opportunity to find out the actual cause of
      death in which the cause of death is suspicious. Sometimes the cause of death
      found through postmortem examination is different from the clinical cause of
      death. The autopsy finding on the cause of death will help doctors even to think
      about unusual conditions that lead to death and hence apply preventive measures
      for those unusual conditions. The cause of medical error is not always due to the
      doctor's mistake, but sometimes also due to the obsolete hospital protocol. The
      autopsy reporting of medical errors can be used to identify lacunae in hospital
      protocols, problem-prone clinical processes and suggest interventions that may
      reduce negligence.

PMID- 29016596
TI  - Experiences of operational costs of HPV vaccine delivery strategies in Gavi
      supported demonstration projects.
AB  - From 2012 to 2016, Gavi, the Vaccine Alliance, provided support for countries to
      conduct small-scale demonstration projects for the introduction of the human
      papillomavirus vaccine, with the aim of determining which human papillomavirus
      vaccine delivery strategies might be effective and sustainable upon national
      scale-up. This study reports on the operational costs and cost determinants of
      different vaccination delivery strategies within these projects across twelve
      countries using a standardized micro-costing tool. The World Health Organization
      Cervical Cancer Prevention and Control Costing Tool was used to collect costing
      data, which were then aggregated and analyzed to assess the costs and cost
      determinants of vaccination. Across the one-year demonstration projects, the
      average economic and financial costs per dose amounted to US$19.98 (standard
      deviation +/-12.5) and US$8.74 (standard deviation +/-5.8), respectively. The
      greatest activities representing the greatest share of financial costs were
      social mobilization at approximately 30% (range, 6-67%) and service delivery at
      about 25% (range, 3-46%). Districts implemented varying combinations of school
      based, facility-based, or outreach delivery strategies and experienced wide
      variation in vaccine coverage, drop-out rates, and service delivery costs,
      including transportation costs and per diems. Size of target population, number
      of students per school, and average length of time to reach an outreach post
      influenced cost per dose. Although the operational costs from demonstration
      projects are much higher than those of other routine vaccine immunization
      programs, findings from our analysis suggest that HPV vaccination operational
      costs will decrease substantially for national introduction. Vaccination costs
      may be decreased further by annual vaccination, high initial investment in social
      mobilization, or introducing/strengthening school health programs. Our analysis
      shows that drivers of cost are dependent on country and district characteristics.
      We therefore recommend that countries carry out detailed planning at the national
      and district levels to define a sustainable strategy for national HPV vaccine
      roll-out, in order to achieve the optimal balance between coverage and cost.

PMID- 29016597
TI  - The clinical utility and cost impact of cystatin C measurement in the diagnosis
      and management of chronic kidney disease: A primary care cohort study.
AB  - BACKGROUND: To reduce over-diagnosis of chronic kidney disease (CKD) resulting
      from the inaccuracy of creatinine-based estimates of glomerular filtration rate
      (GFR), UK and international guidelines recommend that cystatin-C-based estimates
      of GFR be used to confirm or exclude the diagnosis in people with GFR 45-59
      ml/min/1.73 m2 and no albuminuria (CKD G3aA1). Whilst there is good evidence for
      cystatin C being a marker of GFR and risk in people with CKD, its use to define
      CKD in this manner has not been evaluated in primary care, the setting in which
      most people with GFR in this range are managed. METHODS AND FINDINGS: A total of
      1,741 people with CKD G3a or G3b defined by 2 estimated GFR (eGFR) values more
      than 90 days apart were recruited to the Renal Risk in Derby study between June
      2008 and March 2010. Using Chronic Kidney Disease Epidemiology Collaboration (CKD
      EPI) equations, we compared GFR estimated from creatinine (eGFRcreat), cystatin C
      (eGFRcys), and both (eGFRcreat-cys) at baseline and over 5 years of follow-up. We
      analysed the proportion of participants with CKD G3aA1 reclassified to 'no CKD'
      or more advanced CKD with the latter two equations. We further assessed the
      impact of using cystatin-C-based eGFR in risk prediction equations for CKD
      progression and all-cause mortality and investigated non-GFR determinants of
      eGFRcys. Finally, we estimated the cost implications of implementing National
      Institute for Health and Care Excellence (NICE) guidance to use eGFRcys to
      confirm the diagnosis in people classified as CKD G3aA1 by eGFRcreat. Mean
      eGFRcys was significantly lower than mean eGFRcreat (45.1 ml/min/1.73 m2, 95% CI
      44.4 to 45.9, versus 53.6 ml/min/1.73 m2, 95% CI 53.0 to 54.1, P < 0.001).
      eGFRcys reclassified 7.7% (50 of 653) of those with CKD G3aA1 by eGFRcreat to
      eGFR >= 60 ml/min/1.73 m2. However, a much greater proportion (59.0%, 385 of 653)
      were classified to an eGFR category indicating more severe CKD. A similar pattern
      was seen using eGFRcreat-cys, but lower proportions were reclassified. Change in
      eGFRcreat and eGFRcys over 5 years were weakly correlated (r = 0.33, P < 0.001),
      but eGFRcys identified more people as having CKD progression (18.2% versus
      10.5%). Multivariable analysis using eGFRcreat as an independent variable
      identified age, smoking status, body mass index, haemoglobin, serum uric acid,
      serum albumin, albuminuria, and C reactive protein as non-GFR determinants of
      eGFRcys. Use of eGFRcys or eGFRcreat-cys did not improve discrimination in risk
      prediction models for CKD progression and all-cause mortality compared to similar
      models with eGFRcreat. Application of the NICE guidance, which assumed cost
      savings, to participants with CKD G3aA1 increased the cost of monitoring by L23
      per patient, which if extrapolated to be applied throughout England would
      increase the cost of testing and monitoring CKD by approximately L31 million per
      year. Limitations of this study include the lack of a measured GFR and the
      potential lack of ethnic diversity in the study cohort. CONCLUSIONS:
      Implementation of current guidelines on eGFRcys testing in our study population
      of older people in primary care resulted in only a small reduction in diagnosed
      CKD but classified a greater proportion as having more advanced CKD than
      eGFRcreat. Use of eGFRcys did not improve risk prediction in this population and
      was associated with increased cost. Our data therefore do not support
      implementation of these recommendations in primary care. Further studies are
      warranted to define the most appropriate clinical application of eGFRcys and
      eGFRcreat-cys.

PMID- 29016598
TI  - Quantifying underreporting of law-enforcement-related deaths in United States
      vital statistics and news-media-based data sources: A capture-recapture analysis.
AB  - BACKGROUND: Prior research suggests that United States governmental sources
      documenting the number of law-enforcement-related deaths (i.e., fatalities due to
      injuries inflicted by law enforcement officers) undercount these incidents. The
      National Vital Statistics System (NVSS), administered by the federal government
      and based on state death certificate data, identifies such deaths by assigning
      them diagnostic codes corresponding to "legal intervention" in accordance with
      the International Classification of Diseases-10th Revision (ICD-10). Newer,
      nongovernmental databases track law-enforcement-related deaths by compiling news
      media reports and provide an opportunity to assess the magnitude and determinants
      of suspected NVSS underreporting. Our a priori hypotheses were that
      underreporting by the NVSS would exceed that by the news media sources, and that
      underreporting rates would be higher for decedents of color versus white,
      decedents in lower versus higher income counties, decedents killed by non-firearm
      (e.g., Taser) versus firearm mechanisms, and deaths recorded by a medical
      examiner versus coroner. METHODS AND FINDINGS: We created a new US-wide dataset
      by matching cases reported in a nongovernmental, news-media-based dataset
      produced by the newspaper The Guardian, The Counted, to identifiable NVSS
      mortality records for 2015. We conducted 2 main analyses for this cross-sectional
      study: (1) an estimate of the total number of deaths and the proportion
      unreported by each source using capture-recapture analysis and (2) an assessment
      of correlates of underreporting of law-enforcement-related deaths (demographic
      characteristics of the decedent, mechanism of death, death investigator type
      [medical examiner versus coroner], county median income, and county urbanicity)
      in the NVSS using multilevel logistic regression. We estimated that the total
      number of law-enforcement-related deaths in 2015 was 1,166 (95% CI: 1,153,
      1,184). There were 599 deaths reported in The Counted only, 36 reported in the
      NVSS only, 487 reported in both lists, and an estimated 44 (95% CI: 31, 62) not
      reported in either source. The NVSS documented 44.9% (95% CI: 44.2%, 45.4%) of
      the total number of deaths, and The Counted documented 93.1% (95% CI: 91.7%,
      94.2%). In a multivariable mixed-effects logistic model that controlled for all
      individual- and county-level covariates, decedents injured by non-firearm
      mechanisms had higher odds of underreporting in the NVSS than those injured by
      firearms (odds ratio [OR]: 68.2; 95% CI: 15.7, 297.5; p < 0.01), and
      underreporting was also more likely outside of the highest-income-quintile
      counties (OR for the lowest versus highest income quintile: 10.1; 95% CI: 2.4,
      42.8; p < 0.01). There was no statistically significant difference in the odds of
      underreporting in the NVSS for deaths certified by coroners compared to medical
      examiners, and the odds of underreporting did not vary by race/ethnicity. One
      limitation of our analyses is that we were unable to examine the characteristics
      of cases that were unreported in The Counted. CONCLUSIONS: The media-based
      source, The Counted, reported a considerably higher proportion of law-enforcement
      related deaths than the NVSS, which failed to report a majority of these
      incidents. For the NVSS, rates of underreporting were higher in lower income
      counties and for decedents killed by non-firearm mechanisms. There was no
      evidence suggesting that underreporting varied by death investigator type
      (medical examiner versus coroner) or race/ethnicity.

PMID- 29016599
TI  - Coronary collateralization shows sex and racial-ethnic differences in obstructive
      artery disease patients.
AB  - BACKGROUND: Coronary collateral circulation protects cardiac tissues from
      myocardial infarction damage and decreases sudden cardiac death. So far, it is
      unclear how coronary collateralization varies by race-ethnicity groups and by
      sex. METHODS: We assessed 868 patients with obstructive CAD. Patients were
      assessed for collateral grades based on Rentrop grading system, as well as other
      covariates. DNA samples were genotyped using the Affymetrix 6.0 genotyping array.
      To evaluate genetic contributions to collaterals, we performed admixture mapping
      using logistic regression with estimated local and global ancestry. RESULTS:
      Overall, 53% of participants had collaterals. We found difference between sex and
      racial-ethnic groups. Men had higher rates of collaterals than women (P-value =
      0.000175). White Hispanics/Latinos showed overall higher rates of collaterals
      than African Americans and non-Hispanic Whites (59%, 50% and 48%, respectively, P
      value = 0.017), and especially higher rates in grade 1 and grade 3
      collateralization than the other two populations (P-value = 0.0257). Admixture
      mapping showed Native American ancestry was associated with the presence of
      collaterals at a region on chromosome 17 (chr17:35,243,142-41,251,931, beta =
      0.55, P-value = 0.000127). African ancestry also showed association with
      collaterals at a different region on chromosome 17 (chr17: 32,266,966-34,463,323,
      beta = 0.38, P-value = 0.00072). CONCLUSIONS: In our study, collateralization
      showed sex and racial-ethnic differences in obstructive CAD patients. We
      identified two regions on chromosome 17 that were likely to harbor genetic
      variations that influenced collateralization.

PMID- 29016600
TI  - General principles of binding between cell surface receptors and multi-specific
      ligands: A computational study.
AB  - The interactions between membrane receptors and extracellular ligands control
      cell-cell and cell-substrate adhesion, and environmental responsiveness by
      representing the initial steps of cell signaling pathways. These interactions can
      be spatial-temporally regulated when different extracellular ligands are
      tethered. The detailed mechanisms of this spatial-temporal regulation, including
      the competition between distinct ligands with overlapping binding sites and the
      conformational flexibility in multi-specific ligand assemblies have not been
      quantitatively evaluated. We present a new coarse-grained model to realistically
      simulate the binding process between multi-specific ligands and membrane
      receptors on cell surfaces. The model simplifies each receptor and each binding
      site in a multi-specific ligand as a rigid body. Different numbers or types of
      ligands are spatially organized together in the simulation. These designs were
      used to test the relation between the overall binding of a multi-specific ligand
      and the affinity of its cognate binding site. When a variety of ligands are
      exposed to cells expressing different densities of surface receptors, we
      demonstrated that ligands with reduced affinities have higher specificity to
      distinguish cells based on the relative concentrations of their receptors.
      Finally, modification of intramolecular flexibility was shown to play a role in
      optimizing the binding between receptors and ligands. In summary, our studies
      bring new insights to the general principles of ligand-receptor interactions.
      Future applications of our method will pave the way for new strategies to
      generate next-generation biologics.

PMID- 29016601
TI  - Firearm-Related Injury and Death: A U.S. Health Care Crisis in Need of Health
      Care Professionals.
AB  - The U.S.-based Editors of ICMJE journals call for health-care professionals to
      act against the public health crisis of injury and death from guns.

PMID- 29016602
TI  - Relationship between parenting stress and informant discrepancies on symptoms of
      ADHD/ODD and internalizing behaviors in preschool children.
AB  - Parent and teacher ratings of child behaviors are often discrepant, and these
      discrepancies may be correlated with parenting stress. The present study explored
      whether various parenting stress factors are associated with discrepancies
      between parent and teacher ratings of attention-deficit/hyperactivity disorder
      and oppositional defiant disorder (ODD) as well as internalizing symptoms in
      preschool children. We recruited 299 Taiwanese preschool children (aged 4-6
      years) from the community or via clinical referrals. A structural equation
      modeling was used to analyze the relationships among three factors derived from
      the Parenting Stress Index-Short Form and informant discrepancies on symptoms of
      inattention, hyperactivity/impulsivity, ODD, and internalizing behaviors. Scores
      reported by parents were higher for each of the symptoms examined than those
      reported by teachers, and the degree of agreement between informants ranged from
      low to moderate. The parental distress factor of parenting stress was associated
      only with parent ratings, whereas other factors of parenting stress-parent-child
      dysfunctional interaction and parents' stress resulted from their child's
      temperament-were correlated with both parent and teacher ratings. Only parental
      distress factor predicted informant discrepancies for all behavioral symptoms
      assessed. Our findings suggest that parental distress should be considered when
      parent rating scores show significant discrepancies from that of teacher rating
      scores.

PMID- 29016603
TI  - Characterization of hepatitis B virus in Amerindian children and mothers from
      Amazonas State, Colombia.
AB  - BACKGROUND: Hepatitis B Virus (HBV) infection is a worldwide public health
      problem. In the 1980's a highly effective and safe vaccine against HBV was
      developed, although breakthrough infection still occasionally occurs because of
      the emergence of escape mutants. The aim of this study was to identify HBV
      genotypes and escape mutants in children and their mothers in Amerindian
      communities of the Amazonas State, Southern Colombia. METHODS: Blood specimens
      collected from children and mothers belonging to 37 Amerindian communities in
      Amazonas state, were screened for HBsAg and anti-HBc using ELISA. The partial
      region containing the S ORF was amplified by nested PCR, and amplicons were
      sequenced. The phylogenetic analysis was performed using the MEGA 5.05 software.
      RESULTS: Forty-six children (46/1275, 3.6%) and one hundred and seventy-seven
      mothers (177/572, 30.9%) were tested positive for the anti-HBc serological
      marker. Among them, 190 samples were tested for viral genome detection; 8.3%
      (2/31) serum samples obtained from children and 3.1% (5/159) from mothers were
      positive for the ORF S PCR. The predominant HBV genotype in the study population
      was F, subgenotype F1b; in addition, subgenotype F1a and genotype A were also
      characterized. Two HBV escape mutants were identified, G145R, reported worldwide,
      and W156*; this stop codon was identified in a child with occult HBV infection.
      Other mutations were found, L109R and G130E, located in critical positions of the
      HBsAg sequence. CONCLUSIONS: This study aimed to characterize the HBV genotype F,
      subgenotypes F1b and F1a, and genotype A in Amerindian communities and for the
      first time escape mutants in Colombia. Further investigations are necessary to
      elucidate the frequency and the epidemiological impact of the escape mutants in
      the country.

PMID- 29016604
TI  - Novel fine-scale aerial mapping approach quantifies grassland weed cover dynamics
      and response to management.
AB  - Invasive weeds threaten the biodiversity and forage productivity of grasslands
      worldwide. However, management of these weeds is constrained by the practical
      difficulty of detecting small-scale infestations across large landscapes and by
      limits in understanding of landscape-scale invasion dynamics, including
      mechanisms that enable patches to expand, contract, or remain stable. While high
      end hyperspectral remote sensing systems can effectively map vegetation cover,
      these systems are currently too costly and limited in availability for most land
      managers. We demonstrate application of a more accessible and cost-effective
      remote sensing approach, based on simple aerial imagery, for quantifying weed
      cover dynamics over time. In California annual grasslands, the target communities
      of interest include invasive weedy grasses (Aegilops triuncialis and Elymus caput
      medusae) and desirable forage grass species (primarily Avena spp. and Bromus
      spp.). Detecting invasion of annual grasses into an annual-dominated community is
      particularly challenging, but we were able to consistently characterize these two
      communities based on their phenological differences in peak growth and senescence
      using maximum likelihood supervised classification of imagery acquired twice per
      year (in mid- and end-of season). This approach permitted us to map weed
      dominated cover at a 1-m scale (correctly detecting 93% of weed patches across
      the landscape) and to evaluate weed cover change over time. We found that weed
      cover was more pervasive and persistent in management units that had no
      significant grazing for several years than in those that were grazed, whereas
      forage cover was more abundant and stable in the grazed units. This application
      demonstrates the power of this method for assessing fine-scale vegetation
      transitions across heterogeneous landscapes. It thus provides means for small
      scale early detection of invasive species and for testing fundamental questions
      about landscape dynamics.

PMID- 29016605
TI  - Cognitive impairment in hemodialysis patients: Implementation of cut-off values
      for the Montreal Cognitive Assessment (MoCA)-test for feasible screening.
AB  - OBJECTIVE: Reliable identification of cognitive impairment in hemodialysis
      patients is of utmost importance, as it is associated with poor outcomes
      including dialysis withdrawal and death. High prevalence of cognitive impairment
      has been demonstrated in several studies using brief screening instruments or
      neuropsychological test batteries. However, the relevance of cognitive impairment
      as well as the accuracy of screening procedures have never been studied in this
      patient population. METHODS: 151 chronic hemodialysis patients (mean age 65.78 +/
      14.88 years, 73,5% male) underwent cognitive testing under standardized
      conditions by the Montreal Cognitive Assessment (MoCA) and, in a second step, the
      Clinical Dementia Rating scale (CDR), an international standard to measure the
      severity of dementia. For calculating MoCA cut-off values on the basis of the CDR
      global score, receiver operator characteristics (ROC) analysis and c-statistic
      were applied. RESULTS: 49.0% of patients were categorized as 0.5 in the CDR
      global with memory being the predominantly affected domain (47.7% of patients
      scored >= 0.5). Youden's Index led to a threshold of 23.5 points for the MoCA
      test for optimal differentiation between cognitively normal (CDR global < 0.5)
      and impaired patients (CDR global >= 0.5) based on a sensitivity of approximately
      99% and a specificity of approximately 74%. CONCLUSION: Interference of cognitive
      impairment with patients' independence and daily life was shown using the CDR for
      the first time in hemodialysis patients. A MoCA score of 23.5 points turned out
      as optimal threshold to differentiate between patients with and without
      functional impairment in the CDR, thereby paving the way for implementation of
      the MoCA test as a quick and thus highly feasible screening instrument for
      periodic testing in clinical routine.

PMID- 29016606
TI  - Neural coding in the visual system of Drosophila melanogaster: How do small
      neural populations support visually guided behaviours?
AB  - All organisms wishing to survive and reproduce must be able to respond adaptively
      to a complex, changing world. Yet the computational power available is
      constrained by biology and evolution, favouring mechanisms that are parsimonious
      yet robust. Here we investigate the information carried in small populations of
      visually responsive neurons in Drosophila melanogaster. These so-called 'ring
      neurons', projecting to the ellipsoid body of the central complex, are reported
      to be necessary for complex visual tasks such as pattern recognition and visual
      navigation. Recently the receptive fields of these neurons have been mapped,
      allowing us to investigate how well they can support such behaviours. For
      instance, in a simulation of classic pattern discrimination experiments, we show
      that the pattern of output from the ring neurons matches observed fly behaviour.
      However, performance of the neurons (as with flies) is not perfect and can be
      easily improved with the addition of extra neurons, suggesting the neurons'
      receptive fields are not optimised for recognising abstract shapes, a conclusion
      which casts doubt on cognitive explanations of fly behaviour in pattern
      recognition assays. Using artificial neural networks, we then assess how easy it
      is to decode more general information about stimulus shape from the ring neuron
      population codes. We show that these neurons are well suited for encoding
      information about size, position and orientation, which are more relevant
      behavioural parameters for a fly than abstract pattern properties. This leads us
      to suggest that in order to understand the properties of neural systems, one must
      consider how perceptual circuits put information at the service of behaviour.

PMID- 29016607
TI  - Incidence and severity of self-reported chemotherapy side effects in routine
      care: A prospective cohort study.
AB  - AIM: Chemotherapy side effects are often reported in clinical trials; however,
      there is little evidence about their incidence in routine clinical care. The
      objective of this study was to describe the frequency and severity of patient
      reported chemotherapy side effects in routine care across treatment centres in
      Australia. METHODS: We conducted a prospective cohort study of individuals with
      breast, lung or colorectal cancer undergoing chemotherapy. Side effects were
      identified by patient self-report. The frequency, prevalence and incidence rates
      of side effects were calculated by cancer type and grade, and cumulative
      incidence curves for each side effect computed. Frequencies of side effects were
      compared between demographic subgroups using chi-squared statistics. RESULTS:
      Side effect data were available for 449 eligible individuals, who had a median
      follow-up of 5.64 months. 86% of participants reported at least one side effect
      during the study period and 27% reported a grade IV side effect, most commonly
      fatigue or dyspnoea. Fatigue was the most common side effect overall (85%),
      followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence
      rates were similar across side effects and cancer types. Age was the only
      demographic factor associated with the incidence of side effects, with older
      people less likely to report side effects. CONCLUSION: This research has produced
      the first Australian estimates of self-reported incidence of chemotherapy side
      effects in routine clinical care. Chemotherapy side effects in routine care are
      common, continue throughout chemotherapy and can be serious. This work confirms
      the importance of observational data in providing clinical practice-relevant
      information to decision-makers.

PMID- 29016608
TI  - Military service, deployments, and exposures in relation to amyotrophic lateral
      sclerosis survival.
AB  - BACKGROUND: Military veterans may have higher rates of amyotrophic lateral
      sclerosis (ALS) mortality than non-veterans. Few studies, with sparse exposure
      information and mixed results, have studied relationships between military
      related factors and ALS survival. We evaluated associations between military
      related factors and ALS survival among U.S. military veteran cases. METHODS: We
      followed 616 medical record-confirmed cases from enrollment (2005-2010) in the
      Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis
      study until death or July 25, 2013, whichever came first. We ascertained vital
      status information from several sources within the Department of Veterans
      Affairs. We obtained information regarding military service, deployments, and 39
      related exposures via standardized telephone interviews. We used Cox proportional
      hazards regression models to estimate hazard ratios (HRs) and 95% confidence
      intervals. We adjusted for potential confounding and missing covariate data
      biases via inverse probability weights. We also used inverse probability weights
      to adjust for potential selection bias among a case group that included a
      disproportionate number of long-term survivors at enrollment. RESULTS: We
      observed 446 deaths during 24,267 person-months of follow-up (median follow-up:
      28 months). Survival was shorter for cases who served before 1950, were deployed
      to World War II, or mixed and applied burning agents, with HRs between 1.58 and
      2.57. Longer survival was associated with exposure to: paint, solvents, or
      petrochemical substances; local food not provided by the Armed Forces; or burning
      agents or Agent Orange in the field with HRs between 0.56 and 0.73. CONCLUSIONS:
      Although most military-related factors were not associated with survival,
      associations we observed with shorter survival are potentially important because
      of the large number of military veterans.

PMID- 29016610
TI  - Association between a 17-gene genomic prostate score and multi-parametric
      prostate MRI in men with low and intermediate risk prostate cancer (PCa).
AB  - BACKGROUND: We aimed to directly compare results from multi-parametric prostate
      MRI (mpMRI) and a biopsy-based 17-gene RT-PCR assay providing a Genomic Prostate
      Score (GPS) among individuals who were candidates for active surveillance with
      low and intermediate risk prostate cancer (PCa). PATIENTS AND METHODS: We
      evaluated the association between GPS results (scale 0-100) and endorectal mpMRI
      findings in men with clinically localized PCa. MR studies were reviewed to a five
      tier scale of increasing suspicion of malignancy. Mean apparent diffusion
      coefficient (ADC) was calculated from a single dominant lesion. Mean rank of the
      GPS (0-100) among MRI strata was compared with the Kruskal-Wallis test and Dunn's
      multiple comparison test. Spearman's correlation was performed to examine the
      association between mean ADC and scaled GPS. RESULTS: Of 186 patients who
      received GPS testing, 100 were identified who received mpMRI. Mean GPS results
      differed between mpMRI categories (p = 0.001); however a broad range was observed
      in all mpMRI categories. Among men with biopsy Gleason pattern 3+3, mean GPS
      results were not significantly different among MRI groups (p = 0.179), but GPS
      differences were seen among MRI categories for patients with pattern 3+4 (p =
      0.010). Mean ADC was weakly associated with GPS (sigma = -0.151). Stromal
      response (p = 0.015) and cellular organization (p = 0.045) gene group scores
      differed significantly by MRI findings, but no differences were seen among
      androgen signaling or proliferation genes. CONCLUSIONS: Although a statistically
      significant association was observed between GPS results and MRI scores, a wide
      range of GPS values were observed across imaging categories suggesting that mpMRI
      and genomic profiling may offer non- overlapping clinical insights.

PMID- 29016609
TI  - Galectin-3 alters the lateral mobility and clustering of beta1-integrin
      receptors.
AB  - Glycoprotein receptors are influenced by myriad intermolecular interactions at
      the cell surface. Specific glycan structures may interact with endogenous lectins
      that enforce or disrupt receptor-receptor interactions. Glycoproteins bound by
      multivalent lectins may form extended oligomers or lattices, altering the lateral
      mobility of the receptor and influencing its function through endocytosis or
      changes in activation. In this study, we have examined the interaction of
      Galectin-3 (Gal-3), a human lectin, with adhesion receptors. We measured the
      effect of recombinant Gal-3 added exogenously on the lateral mobility of the
      alpha5beta1 integrin on HeLa cells. Using single-particle tracking (SPT) we
      detected increased lateral mobility of the integrin in the presence of Gal-3,
      while its truncated C-terminal domain (Gal-3C) showed only minor reductions in
      lateral mobility. Treatment of cells with Gal-3 increased beta1-integrin mediated
      migration with no apparent changes in viability. In contrast, Gal-3C decreased
      both cell migration and viability. Fluorescence microscopy allowed us to confirm
      that exogenous Gal-3 resulted in reorganization of the integrin into larger
      clusters. We used a proteomics analysis to confirm that cells expressed
      endogenous Gal-3, and found that addition of competitive oligosaccharide ligands
      for the lectin altered the lateral mobility of the integrin. Together, our
      results are consistent with a Gal-3-integrin lattice model of binding and confirm
      that the lateral mobility of integrins is natively regulated, in part, by
      galectins.

PMID- 29016611
TI  - The high-pathogenicity island (HPI) promotes flagellum-mediated motility in
      extraintestinal pathogenic Escherichia coli.
AB  - The key of success of extraintestinal pathogenic Escherichia coli (ExPEC) to
      colonize niches outside the intestinal tract and to establish infection is the
      coordinated action of numerous virulence and fitness factors. The so-called high
      pathogenicity island (HPI), responsible for synthesis, secretion and uptake of
      the siderophore yersiniabactin, proved to be an important virulence determinant.
      In this study we investigated the interaction of the flagellum-mediated motility
      and the HPI. The impairment of yersiniabactin production by deletion of irp2 or
      ybtA affected significantly motility. The gain of yersiniabactin production
      improved motility in both pathogenic and non-pathogenic E. coli strains. The loss
      of flagella expression had no adverse effect on the HPI. Strikingly, external
      iron abundance was not able to suppress activation of the HPI during motility.
      The HPI activity of swarming bacteria was comparable to iron deplete conditions,
      and could even be maximized by supplementing excessive iron. This fact is the
      first description of a regulatory mechanism, which does not follow the known
      hierarchical regulation of siderophore systems. Transcriptional reporter fusions
      of the ybtA promoter demonstrated that the entire promoter region with all YbtA
      binding sites is necessary for complete induction in both HPI-positive and HPI
      negative strains. Altogether, these results suggest that the HPI is part of a
      complex regulatory network, which orchestrates various virulence mechanisms to
      optimize the overall fitness of ExPEC.

PMID- 29016612
TI  - The influence of anonymous peers on prosocial behavior.
AB  - BACKGROUND: Peer influence on students' maladaptive behaviors has been well
      documented; however, the influence on positive development is less acknowledged.
      PURPOSE: The purpose of this study was to examine anonymous peer influence on
      college students' prosocial behavior, specifically behavior for the improvement
      of society (i.e., donating money or participating in social campaigns) via an
      experimental approach. The effects of indirect peer influence (IP) and direct
      peer influence (DP) on college students' prosocial behavior were examined.
      METHODS: A total of 125 college students participated in an online survey and
      laboratory experiment. Self-reported helping behavior, social concern goals, and
      empathy were measured by the online survey. In the laboratory experiments,
      reading of a prosocial paragraph (IP) and confederates' prosocial behavior (DP)
      were manipulated. Participation in a signature campaign and money donation for
      illness were observed. Furthermore, 19 participants among those who donated were
      asked about their reasons for participating in such prosocial behavior. RESULTS:
      Prosocial behavior of anonymous peers (confederates) exerts a profound influence
      on college students' participation in a signature campaign and money donation,
      whereas the reading of a prosocial paragraph has no effect. Furthermore, no
      participants reported peer influence as a reason for engaging in prosocial
      behavior. CONCLUSION: This finding supports and extends recent research examining
      the positive impacts of anonymous peers on prosocial behavior. Prosocial behavior
      is not only a foundational and consistent aspect of personality, as previous
      studies report, but is also highly malleable and unstable in response to
      immediate situations.

PMID- 29016614
TI  - Patterns and rates of abdominal lymphatic metastasis following esophageal
      carcinoma.
AB  - AIM: To determine the rate of abdominal lymph node metastasis after radical
      surgery for esophageal cancer and define the radiotherapy target area. METHODS:
      Of the 1593 patients who underwent R0 radical esophagectomy for thoracic
      esophageal squamous cell carcinoma (TE-SCC), 148 developed abdominal lymph node
      (LN) metastases within three years of surgery. During that time interval,
      patients were examined by various imaging methods (enhanced computer tomography,
      magnetic resonance imaging, and positron emission tomography-CT) at set time
      points. The emerging recurrence pattern, preferred sites for abdominal
      metastasis, and correlation with added clinical factors were carefully recorded,
      to permit for delineation of a target area for radiotherapy. RESULTS: We found
      postoperative metastatic abdominal LNs in 9.3% of the patients treated for
      esophageal cancer. Lesions in the upper, middle, and lower esophageal segments
      metastasized to abdominal LNs at 2.3%, 7.8%, and 26.6% (P < 0.0001),
      respectively. Of all cases, 4.8% had fewer than two affected LNs, while 20.1% had
      more than three metastatic LNs (P< 0.0001). The metastasis rates of negative and
      positive celiac LNs were 4.6% and 22.7%, respectively. Abdominal LN metastasis
      rates for the following LNs: 16a2 and 16a1 of para-aortic, celiac artery,
      posterior surface of the pancreatic head and common hepatic artery were 64.9%,
      41.2%, 37.8%, 32.4%, and 20.9%, respectively. The overall rate of metastasis to
      these groups of LNs was 91.9%. CONCLUSION: This study determined that stations
      16a1 and 16a2 of the para-aortic, truncus coeliacus, posterior surface of the
      pancreatic head, and arteria hepatica communis lymph nodes were the preferred
      sites for abdominal LN metastasis, thus defining target areas for postoperative
      radiotherapy.

PMID- 29016613
TI  - Quantification of carious pathogens in the interdental microbiota of young caries
      free adults.
AB  - BACKGROUND: The majority of caries lesions in adults occur on the proximal tooth
      surfaces of the posterior teeth. A comprehensive study of the composition of the
      oral microbiota is fundamental for a better understanding of the etiology of
      interdental caries. METHODS: Twenty-five caries-free subjects (20-35 years old)
      were enrolled in the study. The interdental biofilm of four interdental sites
      were collected. The real-time polymerase chain reaction (PCR) methodology were
      used to quantify (i) the following bacteria: Streptococcus spp., Streptococcus
      mutans, Lactobacillus spp., Enterococcus spp., and Enterococcus faecalis; (ii)
      the fungus Candida albicans; and (iii) total bacteria. RESULTS: Streptococcus
      spp. was the most abundant species, followed by Lactobacillus spp. and
      Enterococcus spp. Streptococcus spp. and Lactobacillus spp. were detected at all
      tested sites and Enterococcus spp. at 99% of sites. S. mutans was detected at
      only 28% of the tested sites and C. albicans was detected at 11% of sites. E.
      faecalis was never detected. In 54.5% of the biofilm inhabited by C. albicans, S.
      mutans was present. Moreover, 28% of the ID sites co-expressed S. mutans and
      Lactobacillus spp. The studied pathogens were organized into two correlated
      groups of species. Strikingly, the fungus C. albicans and the bacteria
      Enterococcus spp. cluster together, whereas Streptococcus spp., S. mutans and
      Lactobacillus spp. form one distinct cluster. CONCLUSION: The interdental biofilm
      of young caries-free adults is comprised of pathogens that are able to induce
      interproximal caries. That several of these pathogens are implicated in heart
      disease or other systemic diseases is an argument for the disruption of
      interdental biofilms using daily oral hygiene.

PMID- 29016615
TI  - Characterization of the Rotating Exercise Quantification System (REQS), a novel
      Drosophila exercise quantification apparatus.
AB  - Obesity is a disease that has reached epidemic proportions in the United States
      and has prompted international legislation in an attempt to curtail its
      prevalence. Despite the fact that one of the most prescribed treatment options
      for obesity is exercise, the genetic mechanisms underlying exercise response in
      individuals are still largely unknown. The fruit fly Drosophila melanogaster is a
      promising new model for studying exercise genetics. Currently, the lack of an
      accurate method to quantify the amount of exercise performed by the animals is
      limiting the utility of the Drosophila model for exercise genetics research. To
      address this limitation, we developed the Rotational Exercise Quantification
      System (REQS), a novel apparatus that is able to simultaneously induce exercise
      in flies while recording their activity levels. Thus, the REQS provides a method
      to standardize Drosophila exercise and ensure that all animals irrespective of
      genotype and sex experience the same level of exercise. Here, we provide a basic
      characterization of the REQS, validate its measurements using video-tracking
      technology, illustrate its potential use by presenting a comparison of two
      different exercise regimes, and demonstrate that it can be used to detect
      genotype-dependent variation in activity levels.

PMID- 29016617
TI  - MicroRNA-193a inhibits breast cancer proliferation and metastasis by
      downregulating WT1.
AB  - In many cancers, microRNA-193a (miR-193a) is a suppressor miRNA, but its
      underlying anti-oncogenic activity in breast cancer is not known. In this study,
      we found decreased miR-193a (specifically, miR-193a-5p) expression not only in
      breast cancer cell lines but also in breast cancer tissues as compared with the
      adjacent non-tumor tissues. Ectopic miR-193a overexpression inhibited the
      proliferation, colony formation, migration, and invasion of MDA-MB-231 and BT549
      cells. miR-193a reduced Wilms' tumor 1 (WT1) expression and repressed luciferase
      reporter activity by binding WT1 coding region sequences; mutation of the
      predicted miR-193a binding site abolished this effect. miR-193a and WT1
      expression were significantly inversely correlated in breast cancer tissues.
      Importantly, the anti-cancer activity induced by miR-193a was partially reversed
      by WT1 overexpression, indicating an important role for WT1 in such activity
      related to miR-193a. Our results reveal that miR-193a-WT1 interaction plays an
      important role in breast cancer metastasis, and suggest that restoring miR-193a
      expression is a therapeutic strategy in breast cancer.

PMID- 29016616
TI  - A meta-analysis comparing tenotomy and tenodesis for treating rotator cuff tears
      combined with long head of the biceps tendon lesions.
AB  - PURPOSE: The purpose of this meta-analysis was to assess whether there were
      differences in the outcomes between tenotomy and tenodesis in treating LHBT
      lesions combined with rotator cuff repairs. METHODS: Using Medline, Embase, and
      Cochrane, we searched for articles comparing tenotomy and tenodesis combined with
      rotator cuff repair which were published before April 2016 with the terms
      "biceps", "tenotomy", "tenodesis", and "rotator cuff". The controlled clinical
      studies that met the inclusion and exclusion criteria were assessed for quality
      of methodology by utilizing the Coleman score. RESULTS: On the basis of the
      inclusion and exclusion criteria, ten articles (903 patients) were included in
      this meta-analysis. The Coleman score ranged between 40 and 89 in the included
      studies. The results showed that the incidence of the popeye sign (OR, 2.777, P =
      0.000) were higher in tenotomy group compared with tenodesis group when
      concomitant rotator cuff repair. Statistically significant difference in favor of
      tenodesis was observed for Constant score (SMD, -0.230, P = 0.025). As for the
      arm cramping pain, patient satisfaction, VAS score, ASES score and UCLA increased
      score, the strength and the range of motion, there were no significant
      differences between tenodesis and tenotomy of the LHBT, corresponding to the
      currently available results in the literature. CONCLUSIONS: Based on this meta
      analysis, both tenotomy and tenodesis are effective in pain relief and function
      improvement in patients with repairable rotator cuff tears. No significant
      differences in post-operative functional outcome between tenotomy and tenodesis
      for the treatment of LHBT lesions were observed except for a lower Constant score
      and higher risk of Popeye deformity in tenotomy.

PMID- 29016618
TI  - Nigrosome 1 visibility at susceptibility weighted 7T MRI-A dependable diagnostic
      marker for Parkinson's disease or merely an inconsistent, age-dependent imaging
      finding?
AB  - BACKGROUND: Visualisation of nigrosome 1, a substructure of the healthy
      substantia nigra, was restricted in susceptibility weighted MR imaging in almost
      all patients with Parkinson's disease studied so far. The purpose of this study
      was to determine the degree of visibility of this substructure in subjects
      without Parkinson's disease and to examine the potential link between increasing
      brain iron accumulation with age and its detectability. METHODS: In 46 subjects
      (21 women, 25 men; 19 to 75 y; mean age: 44.5; SD: 15.6) examined with
      susceptibility weighted MR imaging at 7T visibility of nigrosome 1 was rated and
      classified. We assessed differences related to age and to signal intensities in
      the substantia nigra, red nucleus and putamen as correlates of the individual
      iron concentration. RESULTS: In 93% nigrosome 1was at least unilaterally clearly
      present. In 24% at least one-sided limited visibility was observed. Using
      predefined classification criteria the specificity of the visibility across all
      age groups reached approximately 94%. We found no correlation with increasing
      iron concentrations with age. CONCLUSION: Aging with a related increase in iron
      concentration probably does not affect the visibility of nigrosome 1 at 7T SWI
      MRI. Our results support the role of this feature as a future differential
      diagnostic tool but further large-scale prospective studies are needed to better
      define the extent of a "limited visibility" to which an individual can be
      considered healthy.

PMID- 29016619
TI  - Tuberculosis mortality and the male survival deficit in rural South Africa: An
      observational community cohort study.
AB  - BACKGROUND: Women live on average five years longer than men, and the sex
      difference in longevity is typically lower in populations with high mortality.
      South Africa-a high mortality population with a large sex disparity-is an
      exception, but the causes of death that contribute to this difference are not
      well understood. METHODS: Using data from a demographic surveillance system in
      rural KwaZulu-Natal (2000-2014), we estimate differences between male and female
      adult life expectancy by HIV status. The contribution of causes of death to these
      life expectancy differences are computed with demographic decomposition
      techniques. Cause of death information comes from verbal autopsy interviews that
      are interpreted with the InSilicoVA tool. RESULTS: Adult women lived an average
      of 10.4 years (95% confidence Interval 9.0-11.6) longer than men. Sex differences
      in adult life expectancy were even larger when disaggregated by HIV status: 13.1
      (95% confidence interval 10.7-15.3) and 11.2 (95% confidence interval 7.5-14.8)
      years among known HIV negatives and positives, respectively. Elevated male
      mortality from pulmonary tuberculosis (TB) and external injuries were responsible
      for 43% and 31% of the sex difference in life expectancy among the HIV negative
      population, and 81% and 16% of the difference among people living with HIV.
      CONCLUSIONS: The sex differences in adult life expectancy in rural KwaZulu-Natal
      are exceptionally large, atypical for an African population, and largely driven
      by high male mortality from pulmonary TB and injuries. This is the case for both
      HIV positive and HIV negative men and women, signalling a need to improve the
      engagement of men with health services, irrespective of their HIV status.

PMID- 29016620
TI  - The EASI model: A first integrative computational approximation to the natural
      history of COPD.
AB  - The natural history of chronic obstructive pulmonary disease (COPD) is still not
      well understood. Traditionally believed to be a self-inflicted disease by
      smoking, now we know that not all smokers develop COPD, that other inhaled
      pollutants different from cigarette smoke can also cause it, and that abnormal
      lung development can also lead to COPD in adulthood. Likewise, the inflammatory
      response that characterizes COPD varies significantly between patients, and not
      all of them perceive symptoms (mostly breathlessness) similarly. To investigate
      the variability and determinants of different "individual natural histories" of
      COPD, we developed a theoretical, multi-stage, computational model of COPD (EASI)
      that integrates dynamically and represents graphically the relationships between
      exposure (E) to inhaled particles and gases (smoking), the biological activity
      (inflammatory response) of the disease (A), the severity (S) of airflow
      limitation (FEV1) and the impact (I) of the disease (breathlessness) in different
      clinical scenarios. EASI shows that the relationships between E, A, S and I vary
      markedly within individuals (through life) and between individuals (at the same
      age). It also helps to delineate some potentially relevant, but often overlooked
      concepts, such as disease progression, susceptibility to COPD and issues related
      to symptom perception. In conclusion, EASI is an initial conceptual model to
      interpret the longitudinal and cross-sectional relationships between E, A, S and
      I in different clinical scenarios. Currently, it does not have any direct
      clinical application, thus it requires experimental validation and further
      mathematical development. However, it has the potential to open novel research
      and teaching alternatives.

PMID- 29016622
TI  - Manganese acquisition is facilitated by PilA in the cyanobacterium Synechocystis
      sp. PCC 6803.
AB  - Manganese is an essential element required by cyanobacteria, as it is an
      essential part of the oxygen-evolving center of photosystem II. In the presence
      of atmospheric oxygen, manganese is present as manganese oxides, which have low
      solubility and consequently provide low bioavailability. It is unknown if
      cyanobacteria are able to utilize these manganese sources, and what mechanisms
      may be employed to do so. Recent evidence suggests that type IV pili in non
      photosynthetic bacteria facilitate electron donation to extracellular electron
      acceptors, thereby enabling metal acquisition. Our present study investigates
      whether PilA1 (major pilin protein of type IV pili) enables the cyanobacterium
      Synechocystis PCC 6808 to access to Mn from manganese oxides. We present
      physiological and spectroscopic data, which indicate that the presence of PilA1
      enhances the ability of cyanobacteria to grow on manganese oxides. These
      observations suggest a role of PilA1-containing pili in cyanobacterial manganese
      acquisition.

PMID- 29016621
TI  - Epidemic dispersion of HIV and HCV in a population of co-infected Romanian
      injecting drug users.
AB  - Co-infections with HIV and HCV are very frequent among people who inject drugs
      (PWID). However, very few studies comparatively reconstructed the transmission
      patterns of both viruses in the same population. We have recruited 117 co
      infected PWID during a recent HIV outbreak in Romania. Phylogenetic analyses were
      performed on HIV and HCV sequences in order to characterize and compare
      transmission dynamics of the two viruses. Three large HIV clusters (2 subtype F1
      and one CRF14_BG) and thirteen smaller HCV transmission networks (genotypes 1a,
      1b, 3a, 4a and 4d) were identified. Eighty (65%) patients were both in HIV and
      HCV transmission chains and 70 of those shared the same HIV and HCV cluster with
      at least one other patient. Molecular clock analysis indicated that all
      identified HIV clusters originated around 2006, while the origin of the different
      HCV clusters ranged between 1980 (genotype 1b) and 2011 (genotypes 3a and 4d).
      HCV infection preceded HIV infection in 80.3% of cases. Coincidental transmission
      of HIV and HCV was estimated to be rather low (19.65%) and associated with an
      outbreak among PWID during detention in the same penitentiary. This study has
      reconstructed and compared the dispersion of these two viruses in a PWID
      population.

PMID- 29016623
TI  - Time frequency analysis of olfactory induced EEG-power change.
AB  - OBJECTIVES: The objective of the present study was to investigate the usefulness
      of time-frequency analysis (TFA) of olfactory-induced EEG change with a low-cost,
      portable olfactometer in the clinical investigation of smell function. MATERIALS
      & METHODS: A total of 78 volunteers participated. The study was composed of three
      parts where olfactory stimuli were presented using a custom-built olfactometer.
      Part I was designed to optimize the stimulus as well as the recording conditions.
      In part II EEG-power changes after olfactory/trigeminal stimulation were compared
      between healthy participants and patients with olfactory impairment. In Part III
      the test-retest reliability of the method was evaluated in healthy subjects.
      RESULTS: Part I indicated that the most effective paradigm for stimulus
      presentation was cued stimulus, with an interstimulus interval of 18-20s at a
      stimulus duration of 1000ms with each stimulus quality presented 60 times in
      blocks of 20 stimuli each. In Part II we found that central processing of
      olfactory stimuli analyzed by TFA differed significantly between healthy controls
      and patients even when controlling for age. It was possible to reliably
      distinguish patients with olfactory impairment from healthy individuals at a high
      degree of accuracy (healthy controls vs anosmic patients: sensitivity 75%;
      specificity 89%). In addition we could show a good test-retest reliability of TFA
      of chemosensory induced EEG-power changes in Part III. CONCLUSIONS: Central
      processing of olfactory stimuli analyzed by TFA reliably distinguishes patients
      with olfactory impairment from healthy individuals at a high degree of accuracy.
      Importantly this can be achieved with a simple olfactometer.

PMID- 29016624
TI  - Unusually high coral recruitment during the 2016 El Nino in Mo'orea, French
      Polynesia.
AB  - The negative implications of the thermal sensitivity of reef corals became clear
      with coral bleaching throughout the Caribbean in the 1980's, and later globally,
      with the severe El Nino of 1998 and extensive seawater warming in 2005. These
      events have substantially contributed to declines in coral cover, and therefore
      the El Nino of 2016 raised concerns over the implications for coral reefs; on the
      Great Barrier Reef these concerns have been realized. A different outcome
      developed in Mo'orea, French Polynesia, where in situ seawater temperature from
      15 March 2016 to 15 April 2016 was an average of 0.4 degrees C above the upper
      95% CI of the decadal mean temperature, and the NOAA Degree Heating Weeks (DHW)
      metric supported a Level 1 bleaching alert (DHW >= 4.0). Starting 1 September
      2016 and for the rest of the year (122 d), in situ seawater temperature was an
      average of 0.4 degrees C above the 95% CI of long-term values, although DHW
      remained at zero. Minor coral bleaching (0.2-2.6% of the coral) occurred on the
      outer reef (10-m and 17-m depth) in April 2016, by May 2016 it had intensified to
      affect 1.3-16.8% of the coral, but by August 2016, only 1.4-3.0% of the coral was
      bleached. Relative to the previous decade, recruitment of scleractinians to
      settlement tiles on the outer- (10 m) and back- (2 m) reef over 2016/17 was high,
      both from January 2016 to August 2016, and from August 2016 to January 2017, with
      increased relative abundances of pocilloporids on the outer reef, and acroporids
      in the back reef. The 2016 El Nino created a distinctive signature in seawater
      temperature for Mo'orea, but it did not cause widespread coral bleaching or
      mortality, rather, it was associated with high coral recruitment. While the 2016
      El Nino has negatively affected other coral reefs in the Indo-Pacific, the coral
      communities of Mo'orea continue to show signs of resilience, thus cautioning
      against general statements regarding the effects of the 2015/16 El Nino on coral
      reefs in the region.

PMID- 29016625
TI  - State-dependent metabolic partitioning and energy conservation: A theoretical
      framework for understanding the function of sleep.
AB  - Metabolic rate reduction has been considered the mechanism by which sleep
      conserves energy, similar to torpor or hibernation. This mechanism of energy
      savings is in conflict with the known upregulation (compared to wake) of diverse
      functions during sleep and neglects a potential role in energy conservation for
      partitioning of biological operations by behavioral state. Indeed, energy savings
      as derived from state-dependent resource allocations have yet to be examined. A
      mathematical model is presented based on relative rates of energy deployment for
      biological processes upregulated during either wake or sleep. Using this model,
      energy savings from sleep-wake cycling over constant wakefulness is computed by
      comparing stable limit cycles for systems of differential equations. A primary
      objective is to compare potential energy savings derived from state-dependent
      metabolic partitioning versus metabolic rate reduction. Additionally, energy
      conservation from sleep quota and the circadian system are also quantified in
      relation to a continuous wake condition. As a function of metabolic partitioning,
      our calculations show that coupling of metabolic operations with behavioral state
      may provide comparatively greater energy savings than the measured decrease in
      metabolic rate, suggesting that actual energy savings derived from sleep may be
      more than 4-fold greater than previous estimates. A combination of state
      dependent metabolic partitioning and modest metabolic rate reduction during sleep
      may enhance energy savings beyond what is achievable through metabolic
      partitioning alone; however, the relative contribution from metabolic
      partitioning diminishes as metabolic rate is decreased during the rest phase.
      Sleep quota and the circadian system further augment energy savings in the model.
      Finally, we propose that state-dependent resource allocation underpins both sleep
      homeostasis and the optimization of daily energy conservation across species.
      This new paradigm identifies an evolutionary selective advantage for the
      upregulation of central and peripheral biological processes during sleep,
      presenting a unifying construct to understand sleep function.

PMID- 29016626
TI  - Effectiveness of proton pump inhibitor in unexplained chronic cough.
AB  - BACKGROUND: Current guidelines recommend that patients with unexplained chronic
      cough undergo empirical proton pump inhibitor (PPI) treatment, but scientific
      evidence for this treatment is lacking. We investigated the effectiveness and
      appropriate dose of PPI therapy in chronic cough. METHODS: We included 27
      patients with unexplained chronic cough after excluding subjects with positive
      response to postnasal drip medication. Subjects were randomized to a placebo,
      standard, and high dose of PPI groups with blinding. The drug or placebo was
      administered orally for 8 weeks, and the Leicester Cough Questionnaire (LCQ)
      score and visual analogue scale (VAS) scores were collected. RESULTS: The LCQ
      score in the PPI group significantly improved from 0 weeks (11.4 +/- 1.4) to 4
      weeks (14.8 +/- 1.4) and to 8 weeks (17.1 +/- 1.4), whereas that in the placebo
      group did not improve from 0 weeks (13.7 +/- 1.1) to 8 weeks (11.8 +/- 1.4); the
      difference between the 2 groups was significant (P < 0.001). In subgroup analysis
      according to reflux, significant improvements in the LCQ score were observed in
      the PPI group regardless of reflux (P < 0.001 in the reflux group and P < 0.001
      in the no reflux group, respectively; P = 0.188 between the 2 groups). In
      addition, improvements in LCQ and VAS scores between the standard- and high-dose
      PPI groups were not significantly different; however, adverse reactions were
      induced by only the high dose (16.7%). CONCLUSIONS: The results of this pilot
      study support the empirical use of the standard dose of PPI for 8 weeks in
      patients suffering from unexplained chronic cough regardless of whether reflux is
      present. TRIAL REGISTRATION: ClinicalTrial.gov NCT01888549
      www.clinicaltrials.gov; cris.nih.go.kr KCT0000543 cris.nih.go.kr/.

PMID- 29016627
TI  - Cost-effectiveness analysis of treatment with non-curative or palliative intent
      for hepatocellular carcinoma in the real-world setting.
AB  - Hepatocellular carcinoma (HCC) presentation is heterogeneous necessitating a
      variety of therapeutic interventions with varying efficacies and associated
      prognoses. Poor prognostic patients often undergo non-curative palliative
      interventions including transarterial chemoembolization (TACE), sorafenib,
      chemotherapy, or purely supportive care. The decision to pursue one of many
      palliative interventions for HCC is complex and an economic evaluation comparing
      these interventions has not been done. This study evaluates the cost
      effectiveness of non-curative palliative treatment strategies such as TACE alone
      or TACE+sorafenib, sorafenib alone, and non-sorafenib chemotherapy compared with
      no treatment or best supportive care (BSC) among patients diagnosed with HCC
      between 2007 and 2010 in a Canadian setting. Using person-level data, we
      estimated effectiveness in life years and quality-adjusted life years (QALYs)
      along with total health care costs (2013 US dollars) from the health care payer's
      perspective (3% annual discount). A net benefit regression approach accounting
      for baseline covariates with propensity score adjustment was used to calculate
      incremental net benefit to generate incremental cost-effectiveness ratio (ICER)
      and uncertainty measures. Among 1,172 identified patients diagnosed with HCC,
      4.5%, 7.9%, and 5.6%, received TACE alone or TACE+sorafenib, sorafenib, and non
      sorafenib chemotherapy clone, respectively. Compared with no treatment or BSC
      (81.9%), ICER estimates for TACE alone or TACE+sorafenib was $6,665/QALY
      (additional QALY: 0.47, additional cost: $3,120; 95% CI: -$18,800-$34,500/QALY).
      The cost-effectiveness acceptability curve demonstrated that if the relevant
      threshold was $50,000/QALY, TACE alone or TACE+sorafenib, non-sorafenib
      chemotherapy, and sorafenib alone, would have a cost-effectiveness probability of
      99.7%, 46.6%, and 5.5%, respectively. Covariates associated with the incremental
      net benefit of treatments are age, sex, comorbidity, and cancer stage. Findings
      suggest that TACE with or without sorafenib is currently the most cost-effective
      active non-curative palliative treatment approach to HCC. Further research into
      new combination treatment strategies that afford the best tumor response is
      needed.

PMID- 29016628
TI  - Hazardous air pollutants and primary liver cancer in Texas.
AB  - The incidence of hepatocellular carcinoma (HCC), the most common primary liver
      cancer, is increasing in the US and tripled during the past two decades. The
      reasons for such phenomenon remain poorly understood. Texas is among continental
      states with the highest incidence of liver cancer with an annual increment of
      5.7%. Established risk factors for HCC include Hepatitis B and C (HBV, HCV) viral
      infection, alcohol, tobacco and suspected risk factors include obesity and
      diabetes. While distribution of these risk factors in the state of Texas is
      similar to the national data and homogeneous, the incidence of HCC in this state
      is exceptionally higher than the national average and appears to be
      dishomogeneous in various areas of the state suggesting that other non-recognized
      risk factors might play a role. No population-based studies are currently
      available investigating the effect of exposure to Hazardous Air Pollutants (HAPs)
      as a contributing risk factor for liver cancer. Incidence rate of liver cancer in
      Texas by counties for the time period between 2002 and 2012 was obtained from the
      Texas Cancer Registry (TCR). Through Principal Component Analysis (PCA) a
      subgroup of pollutants, explaining almost all the dataset variability, were
      identified and used to cluster Texas counties. The analysis generated 4 clusters
      showing liver cancer rate either higher or lower than national average in
      association with either high or low levels of HAPs emission in the environment.
      The study shows that the selected relevant HAPs, 10 among 253 analyzed, produce a
      significant correlation (P = 0.01-0.05) and some of these have been previously
      identified as carcinogens. An association between the increased production and
      consequent exposure to these HAPs and a higher presence of liver cancer in
      certain counties is suggested. This study provides a new insight on this complex
      multifactorial disease suggesting that environmental substances might play a role
      in the etiology of this cancer.

PMID- 29016629
TI  - Three-dimensional morphology of first molars in relation to ethnicity and the
      occurrence of cleft lip and palate.
AB  - OBJECTIVES: This study aims to describe morphological peculiarities of maxillary
      and mandibular first molars in Europeans, Asians and Europeans with cleft lip and
      palate. MATERIAL AND METHODS: Reflex microscopy was used to obtain three
      dimensional morphometric landmarks from 40 models (11 Europeans and 13 Asians
      without cleft lip and palate, 16 Europeans with unilateral cleft lip and palate).
      The cases were examined using traditional morphometry and geometric morphometry,
      and visualized using thin-plate splines. RESULTS: Classic morphometry showed no
      right/left differences in the study groups and no significant differences with
      regard to the cleft side in patients with cleft lip and palate. In Asians, a
      significantly greater mesiodistal width was found. Geometric morphometry showed
      an enlarged centroid size in Asians (maxilla and mandible). In cleft patients,
      the cleft site did not appear to impact the morphology of first molars.
      CONCLUSION: Unilateral clefting did not affect the size and shape of molars;
      however, characteristic ethnicity-based differences were in fact identified. The
      results are relevant for orthodontic treatment with preadjusted appliances, and
      prosthetic CAD/CAM restorations.

PMID- 29016630
TI  - Association between kidney function and genetic polymorphisms in atherosclerotic
      and chronic kidney diseases: A cross-sectional study in Japanese male workers.
AB  - BACKGROUND: Several single nucleotide polymorphisms (SNPs) have been implicated
      in the predisposition to chronic kidney disease (CKD). Atherosclerotic disease is
      deeply involved in the incidence of CKD; however, whether SNPs related to
      arteriosclerosis are involved in CKD remains unclear. This study aimed to
      identify SNPs associated with CKD and to examine whether risk allele accumulation
      is associated with CKD. METHODS: We conducted a cross-sectional study using data
      of 4814 male workers to examine the association between estimated glomerular
      filtration rate (eGFR) and 59 candidate polymorphisms (17 CKD, 42 atherosclerotic
      diseases). We defined the genetic risk score (GRS) as the total number of risk
      alleles that showed a significant association in this analysis and examined the
      relationship with CKD (eGFR < 60 ml/min/1.73m2). Multivariate logistic
      regression, discrimination by area under the receiver operating characteristic
      curve, integrated discrimination improvement (IDI), and category-free net
      reclassification improvement (cNRI) were evaluated. RESULTS: In total, 432
      participants were categorized as having CKD. We found eight candidate SNPs with P
      value < 0.05 (CX3CR1 rs3732379, SHROOM3 rs17319721, MTP rs1800591, PIP5K1B
      rs4744712, APOA5 rs662799, BRAP rs3782886, SPATA5L1 rs2467853, and MCP1
      rs1024611) in the multivariate linear regression adjusted for age, body mass
      index, systolic blood pressure, and fasting blood glucose. Among these eight
      SNPs, BRAP rs3782886 and SPATA5L1 rs2467853 were significantly associated with
      eGFR (false discovery rate < 0.05). GRS was significantly associated with CKD
      (odds ratio, 1.17; 95% confidence interval, 1.09-1.26). C-statisics improved from
      0.775 to 0.780 but showed no statistical significance. However, adding GRS
      significantly improved IDI and cNRI (0.0057, P = 0.0028, and 0.212, P < 0.001,
      respectively). CONCLUSIONS: After adjustment for clinical factors, kidney
      function was associated with BRAP rs3782886 and SPATA5L1 rs2467853 and the GRS
      for CKD that we developed was associated CKD.

PMID- 29016632
TI  - Radial artery neointimal hyperplasia after transradial PCI-Serial optical
      coherence tomography volumetric study.
AB  - AIMS: Transradial catheterization (TRC) is a dominant access site for coronary
      catheterization and percutaneous coronary interventions (PCI) in many centers.
      Previous studies reported higher intimal thickness of the radial artery (RA) wall
      in patients with a previous history of TRC. In this investigation the aim was to
      assess the intimal changes of RA using the optical coherence tomography (OCT)
      intravascular imaging in a serial manner. METHODS AND RESULTS: 100 patients with
      the diagnosis of non-ST-elevation myocardial infarction (nSTEMI) treated by PCI
      were enrolled (6 patients were excluded from this analysis because of occluded RA
      at follow-up [2 patients] and insufficient quality of OCT images [4 patients]).
      An 54mm long OCT run of the RA was performed immediately after the index PCI and
      repeated 9 months later. Volumetric analyses of the intimal layer and lumen
      changes were conducted. Median intimal volume at baseline versus 9 months was
      33.9mm3 (19.0; 69.4) versus 39.0mm3 (21.7; 72.6) (p<0.001); and median arterial
      lumen volume was 356.3mm3 (227.8; 645.3) versus 304.7mm3 (186.1; 582.7)
      (p<0.001). There was no significant difference in the effect of any clinical
      factor on the RA volume changes. CONCLUSIONS: OCT volumetric analyses at baseline
      and 9 months showed a significant increase in the radial artery intimal layer
      volume and a decrease in lumen volume after transradial PCI. No significant
      factors affecting this process were identified.

PMID- 29016631
TI  - A measure of knowledge flow between specific fields: Implications of
      interdisciplinarity for impact and funding.
AB  - Encouraging knowledge flow between mutually relevant disciplines is a worthy aim
      of research policy makers. Yet, it is less clear what types of research promote
      cross-disciplinary knowledge flow and whether such research generates
      particularly influential knowledge. Empirical questions remain as to how to
      identify knowledge-flow mediating research and how to provide support for this
      research. This study contributes to addressing these gaps by proposing a new way
      to identify knowledge-flow mediating research at the individual research article
      level, instead of at more aggregated levels. We identify journal articles that
      link two mutually relevant disciplines in three ways-aggregating, bridging, and
      diffusing. We then examine the likelihood that these papers receive subsequent
      citations or have funding acknowledgments. Our case study of cognitive science
      and educational research knowledge flow suggests that articles that aggregate
      knowledge from multiple disciplines are cited significantly more often than are
      those whose references are drawn primarily from a single discipline.
      Interestingly, the articles that meet the criteria for being considered knowledge
      flow mediators are less likely to reflect funding, based on reported
      acknowledgements, than were those that did not meet these criteria. Based on
      these findings, we draw implications for research policymakers.

PMID- 29016633
TI  - Apparent survival and cost of reproduction for White-lined Tanager (Tachyphonus
      rufus, Thraupidae) in the northern Atlantic Rainforest, Brazil.
AB  - Understanding latitudinal variation in avian life-history traits has been a focus
      of many demographic studies around the world. However, we still know little about
      annual or intra-annual demographic variation within tropical regions or about how
      factors such as breeding season and precipitation influence demographic rates. In
      this study, we estimated intra-annual apparent survival of the White-lined
      Tanager (Tachyphonus rufus) using capture-mark-recapture data from northeastern
      Brazil. We tested whether survival varied seasonally (breeding vs. non-breeding),
      with rainfall, by age and residence status in our study area. Intra-annual
      apparent survival was correlated with the reproductive cycle, being lower during
      the breeding (0.65 +/- 0.16 SE) vs. the non-breeding season (0.97 +/- 0.05 SE).
      The annual apparent survival (~0.6) was relatively low for a tropical species. In
      both years, we observed highest abundance in spring (November, 3.1-3.7 birds/ha)
      and lowest abundance in autumn-winter periods (May-August, 1.1-1.4 bird/ha). The
      low survival during the breeding season probably reflects the trade-off between
      survival and reproduction and the cost of reproduction. Our findings represent an
      advance in the understanding of the demography of tropical birds because we did
      not find a predicted high annual apparent survival, and we elucidated some
      aspects of intra-annual variation in survival. Further exploration of latitudinal
      variation in demographic traits, especially in diverse, but poorly known habitats
      is needed to fully vet and develop life history theories.

PMID- 29016634
TI  - Conventional early infant diagnosis in Lesotho from specimen collection to
      results usage to manage patients: Where are the bottlenecks?
AB  - INTRODUCTION: Early infant diagnosis is an important step in identifying children
      infected with HIV during the perinatal period or in utero. Multiple factors
      contribute to delayed antiretroviral treatment initiation for HIV-infected
      children, including delays in the early infant HIV diagnosis cascade. METHODS: We
      conducted a retrospective study to evaluate early infant diagnosis turnaround
      times in Lesotho. Trained staff reviewed records of HIV-exposed infants (aged-6-8
      weeks) who received an HIV test during 2011. Study sites were drawn from
      Highlands, Foothills and Lowlands regions of Lesotho. Central laboratory database
      data were linked to facility and laboratory register information. Turnaround time
      geometric means (with 95% CI) were calculated and compared by region using linear
      mixed models. RESULTS: 1,187 individual infant records from 25 facilities were
      reviewed. Overall, early infant diagnosis turnaround time was 61.7 days (95%CI:
      55.3-68.7). Mean time from specimen collection to district laboratory was 14 days
      (95%CI: 12.1-16.1); from district to central laboratory, 2 days (95%CI 0.8-5.2);
      results from central laboratory to district hospital, 23.3 days (95%CI: 18.7
      29.0); from district hospital to health facility, 3.2 days (95%CI 1.9-5.5); and
      from health facility to caregiver, 10.4 days (95%CI, 7.9-13.5). Mean times from
      specimen transfer to the central laboratory and for result transfer from central
      laboratory to district hospital were significantly shorter in the Lowlands Region
      (0.9 and 16.2 days, respectively), compared to Highlands Region (6.0 [P = 0.030]
      and 34.3 days [P = 0.0099]. Turnaround time from blood draw to receipt of results
      was significantly shorter for HIV infected infants compared to HIV uninfected
      infants [p = 0.0036] at an average of 47.1 days (95%CI: 38.9-56.9) and 62 days
      (95%CI: 55.9-68.7) respectively. Of 47 HIV-infected infants, 36 were initiated on
      antiretroviral therapy at an average of 1.3 days (95%CI: 0.3, 5.7) after
      caregiver received the result. CONCLUSION: HIV-infected infants received results
      earlier and were rapidly initiated on antiretroviral therapy once the result was
      delivered to caregiver. However, average early infant diagnosis turnaround time
      was two months; the longest period of delay was transfer of results from central
      laboratory to district hospital. Turnaround time of results based on geographical
      regions or between hospitals and health centres varied but did not reach
      statistical significance.

PMID- 29016637
TI  - Social networks, market transactions, and reputation as a central resource. The
      Mercado del Mar, a fish market in central Mexico.
AB  - Fish consumption in Mexico is considered low (around 12 kg per person per year)
      and non-homogeneously distributed across the country. One of the reasons for this
      situation is the scarcity of wholesale selling sites. In this context, the
      Mercado del Mar (MM), located in Guadalajara city, Jalisco, is the second biggest
      wholesale fish market in Mexico, with a distribution of about 500 tons per day
      and a variety of about 350 different species of fish. In this paper, we argue
      that MM has accumulated social capital, which is formed from two main resources:
      buyer and seller relationships, and reputation. Specifically, the MM manages a
      broad and intensive interaction among business actors and the already achieved
      reputation allows the MM to adapt to market changes. To validate our hypotheses,
      an empirical study was conducted in 2015 by means of interviews to fish
      wholesalers in the MM and a sample of their suppliers and buyers. For simplicity
      we have only considered fresh water fish. We have followed snow-ball sampling as
      the survey strategy. Results show that the MM has responded to fish market
      dynamics organizing a complex network of buyers and suppliers whose relationships
      can be explained in the form of strong and weak ties. At the same time,
      reputation has been the central resource to build this social capital and also
      gives place to market transactions. Additionally, the strategic position of
      Guadalajara city and the well-connected routes have facilitated fish bulking and
      distribution in the region.

PMID- 29016636
TI  - Expression of ribosomal proteins in normal and cancerous human prostate tissue.
AB  - Few quantifiable tissue biomarkers for the diagnosis and prognosis of prostate
      cancer exist. Using an unbiased, quantitative approach, this study evaluates the
      potential of three proteins of the 40S ribosomal protein complex as putative
      biomarkers of malignancy in prostate cancer. Prostate tissue arrays, constructed
      from 82 patient samples (245 tissue cores, stage pT3a or pT3b), were stained for
      antibodies against three ribosomal proteins, RPS19, RPS21 and RPS24. Semi
      automated Ox-DAB signal quantification using ImageJ software revealed a
      significant change in expression of RPS19, RPS21 and RPS24 in malignant vs non
      malignant tissue (p<0.0001). Receiver operating characteristics curves were
      calculated to evaluate the potential of each protein as a biomarker of malignancy
      in prostate cancer. Positive likelihood ratios for RPS19, RPS21 and RPS24 were
      calculated as 2.99, 4.21, and 2.56 respectively, indicating that the
      overexpression of the protein is correlated with the presence of disease. Triple
      labelled, quantitative, immunofluorescence (with RPS19, RPS21 and RPS24) showed
      significant changes (p<0.01) in the global intersection coefficient, a measure of
      how often two fluorophore signals intersect, for RPS19 and RPS24 only. No change
      was observed in the co-localization of any other permutations of the three
      proteins. Our results show that RPS19, RPS21 or RPS24 are upregulated in
      malignant tissue and may serve as putative biomarkers for prostate cancer.

PMID- 29016635
TI  - HIV/Human herpesvirus co-infections: Impact on tryptophan-kynurenine pathway and
      immune reconstitution.
AB  - BACKGROUND: Co-infections with human herpesvirus (HHV) have been associated with
      residual chronic inflammation in antiretroviral (ART)-treated human
      immunodeficiency virus (HIV)-infected individuals. However, the role of HHV in
      modulating the tryptophan-kynurenine pathway and clinical outcomes in HIV
      infected individuals is poorly understood. Thus, we investigated the
      seroprevalence of four common HHVs among treated HIV-infected participants and
      their impact on kynurenine/tryptophan (K/T) ratio and long-term CD4 T-cell
      recovery in HIV/HHV co-infected participants. METHOD: In this cross-sectional
      study, HIV-infected participants receiving suppressive ART for a minimum of 12
      months were recruited from the University Malaya Medical Centre (UMMC), Malaysia.
      Stored plasma was analyzed for CMV, VZV, HSV-1 and HSV-2 IgG antibody levels,
      immune activation markers (interleukin-6, interferon-gamma, neopterin and sCD14),
      kynurenine and tryptophan concentrations. The influence of the number of HHV co
      infection and K/T ratio on CD4 T-cell recovery was assessed using multivariate
      Poisson regression. RESULTS: A total of 232 HIV-infected participants were
      recruited and all participants were seropositive for at least one HHV; 96.1% with
      CMV, 86.6% with VZV, 70.7% with HSV-1 and 53.9% with HSV-2. K/T ratio had a
      significant positive correlation with CMV (rho = 0.205, p = 0.002), VZV (rho =
      0.173, p = 0.009) and a tendency with HSV-2 (rho = 0.120, p = 0.070), with CMV
      antibody titer demonstrating the strongest modulating effect on K/T ratio among
      the four HHVs assessed in SOM analysis. In multivariate analysis, higher K/T
      ratio (p = 0.03) and increasing number of HHV co-infections (p<0.001) were
      independently associated with poorer CD4 T-cell recovery following 12 months of
      ART initiation. CONCLUSION: Multiple HHV co-infections are common among ART
      treated HIV-infected participants in the developing country setting and
      associated with persistent immune activation and poorer CD4 T-cell recovery.

PMID- 29016638
TI  - Penile coital injuries in men decline after circumcision: Results from a
      prospective study of recently circumcised and uncircumcised men in western Kenya.
AB  - BACKGROUND: Penile coital injuries are one of the suggested mechanisms behind the
      increased risk of HIV among uncircumcised men. We evaluated the prevalence and
      correlates of self-reported penile coital injuries in a longitudinal community
      based cohort of young (18-24 years old), newly circumcised and uncircumcised men
      in Western Kenya. METHODS: Self-reported penile coital injuries were assessed at
      baseline, 6, 12, 18 and 24 months of follow-up, and were defined as scratches,
      cuts or abrasions during sex, penile soreness during sex, and skin of the penis
      bleeding during sex. Associations between penile coital injuries, circumcision,
      sexual satisfaction, and other covariates were estimated with mixed effect
      models. RESULTS: Between November 2008 and April 2010 3,186 participants were
      enrolled (1,588 into circumcision group and 1,598 as age-matched controls). Among
      2,106 (66%) participants sexually active at baseline, 53% reported any penile
      injury, including 44% scratches, cuts or abrasions; 32% penile pain/soreness; and
      22% penile bleeding. In multivariable modeling, risk was lower for circumcised
      men than uncircumcised men for scratches, cuts and abrasions (aOR = 0.39; 95% CI
      0.34-0.44); penile pain/soreness (aOR = 0.58; 95% CI 0.51-0.65), penile bleeding
      (aOR = 0.53; 95% CI 0.46-0.62), and any penile coital injuries (aOR = 0.47; 95%CI
      0.42-0.53). Other significant risk factors included increasing age, history of
      STIs and genital sores, and multiple sex partners, while condom use was
      protective. Coital injuries were significantly associated with lower levels of
      sexual satisfaction in longitudinal analyses (scratches, cuts or abrasions: aOR =
      0.87, 95% CI: 0.76-0.98; penile pain/soreness: aOR = 0.82, 95% CI: 0.72-0.93; and
      penile bleeding: aOR = 0.65, 95% CI: 0.55-0.76). CONCLUSIONS: Self-reported
      penile coital injuries were common and decreased significantly following
      circumcision. Improving sexual experience through the removal of a potential
      source of sexual discomfort may resonate with many men targeted for circumcision
      services. The role of penile coital injuries in sexual satisfaction, HIV, HSV-2,
      and as a motivator for seeking circumcision services should be explored further.

PMID- 29016639
TI  - Do black lives matter in public health research and training?
AB  - OBJECTIVE: To examine whether investments made in public health research align
      with the health burdens experienced by white and black Americans. METHODS: In
      this cross-sectional study of all deaths in the United States in 2015, we
      compared the distribution of potential years of life lost (PYLL) across 39 causes
      of death by race and identified key differences. We examined the relationship
      between cause-of-death-specific PYLL and key indicators of public health
      investment (federal funding and number of publications) by race using linear
      spline models. We also compared the number of courses available at the top
      schools of public health relevant to the top causes of death contributor to PYLL
      for black and white Americans. RESULTS: Homicide was the number one contributor
      to PYLL among black Americans, while ischemic heart disease was the number one
      contributor to PYLL among white Americans. Firearm-related violence accounted for
      88% of black PYLL attributed to homicide and 71% of white PYLL attributed to
      homicide. Despite the high burden of PYLL, homicide research was the focus of few
      federal grants or publications. In comparison, ischemic heart disease garnered
      341 grants and 594 publications. The number of public health courses available
      relevant to homicide (n = 9) was similar to those relevant to ischemic heart
      disease (n = 10). CONCLUSIONS: Black Americans are disproportionately affected by
      homicide, compared to white Americans. For both black and white Americans, the
      majority of PYLL due to homicide are firearm-related. Yet, homicide research is
      dramatically underrepresented in public health research investments in terms of
      grant funding and publications, despite available public health training
      opportunities. If left unchecked, the observed disproportionate distribution of
      investments in public health resources threatens to perpetuate a system that
      disadvantages black Americans.

PMID- 29016641
TI  - Association of SNP rs80659072 in the ZRS with polydactyly in Beijing You
      chickens.
AB  - The Beijing You chicken is a Chinese native breed with superior meat quality and
      a unique appearance. The G/T mutation of SNP rs80659072 in the Shh long-range
      regulator of GGA2 is highly associated with the polydactyly phenotype in some
      chicken breeds. In the present study, this SNP was genotyped using the TaqMan
      detection method, and its association with the number of toes was analyzed in a
      flock of 158 birds of the Beijing You population maintained at the Beijing
      Academy of Agriculture and Forestry Sciences. Furthermore, the skeletal structure
      of the digits was dissected and assembled in 113 birds. The findings revealed
      that the toes of Beijing You chickens were rich and more complex than expected.
      The plausible mutation rs80659072 in the zone of polarizing activity regulatory
      sequence (ZRS) in chickens was an essential but not sufficient condition for
      polydactyly and polyphalangy in Beijing You chickens. Several individuals shared
      the T allele but showed normal four-digit conformations. However, breeding trials
      demonstrated that the T allele could serve as a strong genetic marker for five
      toe selection in Beijing You chickens.

PMID- 29016642
TI  - Navigating behavioral energy sufficiency. Results from a survey in Swiss cities
      on potential behavior change.
AB  - Many countries have some kind of energy-system transformation either planned or
      ongoing for various reasons, such as to curb carbon emissions or to compensate
      for the phasing out of nuclear energy. One important component of these
      transformations is the overall reduction in energy demand. It is generally
      acknowledged that the domestic sector represents a large share of total energy
      consumption in many countries. Increased energy efficiency is one factor that
      reduces energy demand, but behavioral approaches (known as "sufficiency") and
      their respective interventions also play important roles. In this paper, we
      address citizens' heterogeneity regarding both their current behaviors and their
      willingness to realize their sufficiency potentials-that is, to reduce their
      energy consumption through behavioral change. We collaborated with three Swiss
      cities for this study. A survey conducted in the three cities yielded thematic
      sets of energy-consumption behavior that various groups of participants rated
      differently. Using this data, we identified four groups of participants with
      different patterns of both current behaviors and sufficiency potentials. The
      paper discusses intervention types and addresses citizens' heterogeneity and
      behaviors from a city-based perspective.

PMID- 29016640
TI  - Effects of AAV-mediated knockdown of nNOS and GPx-1 gene expression in rat
      hippocampus after traumatic brain injury.
AB  - Virally mediated RNA interference (RNAi) to knock down injury-induced genes could
      improve functional outcome after traumatic brain injury (TBI); however, little is
      known about the consequences of gene knockdown on downstream cell signaling
      pathways and how RNAi influences neurodegeneration and behavior. Here, we
      assessed the effects of adeno-associated virus (AAV) siRNA vectors that target
      two genes with opposing roles in TBI pathogenesis: the allegedly detrimental
      neuronal nitric oxide synthase (nNOS) and the potentially protective glutathione
      peroxidase 1 (GPx-1). In rat hippocampal progenitor cells, three siRNAs that
      target different regions of each gene (nNOS, GPx-1) effectively knocked down gene
      expression. However, in vivo, in our rat model of fluid percussion brain injury,
      the consequences of AAV-siRNA were variable. One nNOS siRNA vector significantly
      reduced the number of degenerating hippocampal neurons and showed a tendency to
      improve working memory. GPx-1 siRNA treatment did not alter TBI-induced
      neurodegeneration or working memory deficits. Nevertheless, microarray analysis
      of laser captured, virus-infected neurons showed that knockdown of nNOS or GPx-1
      was specific and had broad effects on downstream genes. Since nNOS knockdown only
      modestly ameliorated TBI-induced working memory deficits, despite widespread
      genomic changes, manipulating expression levels of single genes may not be
      sufficient to alter functional outcome after TBI.

PMID- 29016643
TI  - Minimum requirements for motility of a processive motor protein.
AB  - Motor proteins generally have a two-way coupling between the ATP hydrolysis site,
      the lever movement and the binding affinity for their track, which allows them to
      perform efficient stepping. Here we explore the minimal requirements for directed
      motility based on simpler schemes in which the binding/unbinding from the track
      is decoupled from the ATPase cycle. We show that a directed power stroke alone is
      not sufficient for motility, but combined with an asymmetry in force-induced
      unbinding rates it can generate stepping. The energetic efficiency of such
      stepping is limited to approximately 20%. We conclude that the allosteric
      coupling between the ATP hydrolysis and the track binding is not strictly
      necessary for motility, but it greatly improves its efficiency.

PMID- 29016644
TI  - Accuracy of Xpert Clostridium difficile assay for the diagnosis of Clostridium
      difficile infection: A meta analysis.
AB  - BACKGROUND: There is an urgent need for rapid and accurate microbiological
      diagnostic assay for detection of Clostridium difficile infection (CDI). We
      assessed the diagnostic accuracy of the Xpert Clostridium difficile assay (Xpert
      CD) for the diagnosis of CDI. METHODS: We searched PubMed, EMBASE, and Cochrane
      Library databases to identify studies according to predetermined criteria. STATA
      13.0 software was used to analyze the tests for sensitivity, specificity,
      positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and
      area under the summary receiver operating characteristic curves (AUC). QUADAS-2
      was used to assess the quality of included studies with RevMan 5.2. Heterogeneity
      in accuracy measures was tested with Spearman correlation coefficient and Chi
      square. RESULTS: A total of 22 studies were included in the meta-analysis. The
      pooled sensitivity (95% confidence intervals [CI]) was 0.97 (0.95-0.99) and
      specificity was 0.95 (0.94-0.96). The AUC was 0.99 (0.97-0.99). Significant
      heterogeneity was observed when we pooled most of the accuracy measures of
      selected studies. CONCLUSIONS: The Xpert CD assay is a useful diagnostic tool
      with high sensitivity and specificity in diagnosing toxigenic CDI, and this
      method has excellent usability due to its rapidity and simplicity.

PMID- 29016645
TI  - Spontaneous variability of pre-dialysis concentrations of uremic toxins over time
      in stable hemodialysis patients.
AB  - BACKGROUND AND AIM: Numerous outcome studies and interventional trials in
      hemodialysis (HD) patients are based on uremic toxin concentrations determined at
      one single or a limited number of time points. The reliability of these studies
      however entirely depends on how representative these cross-sectional
      concentrations are. We therefore investigated the variability of predialysis
      concentrations of uremic toxins over time. METHODS: Prospectively collected
      predialysis serum samples of the midweek session of week 0, 1, 2, 3, 4, 8, 12,
      and 16 were analyzed for a panel of uremic toxins in stable chronic HD patients
      (N = 18) while maintaining dialyzer type and dialysis mode during the study
      period. RESULTS: Concentrations of the analyzed uremic toxins varied
      substantially between individuals, but also within stable HD patients (intra
      patient variability). For urea, creatinine, beta-2-microglobulin, and some
      protein-bound uremic toxins, Intra-class Correlation Coefficient (ICC) was higher
      than 0.7. However, for phosphorus, uric acid, symmetric and asymmetric
      dimethylarginine, and the protein-bound toxins hippuric acid and indoxyl sulfate,
      ICC values were below 0.7, implying a concentration variability within the
      individual patient even exceeding 65% of the observed inter-patient variability.
      CONCLUSION: Intra-patient variability may affect the interpretation of the
      association between a single concentration of certain uremic toxins and outcomes.
      When performing future outcome and interventional studies with uremic toxins
      other than described here, one should quantify their intra-patient variability
      and take into account that for solutes with a large intra-patient variability
      associations could be missed.

PMID- 29016648
TI  - Recurrence analysis of ant activity patterns.
AB  - In this study, we used recurrence quantification analysis (RQA) and recurrence
      plots (RPs) to compare the movement activity of individual workers of three ant
      species, as well as a gregarious beetle species. RQA and RPs quantify the number
      and duration of recurrences of a dynamical system, including a detailed
      quantification of signals that could be stochastic, deterministic, or both.
      First, we found substantial differences between the activity dynamics of beetles
      and ants, with the results suggesting that the beetles have quasi-periodic
      dynamics and the ants do not. Second, workers from different ant species varied
      with respect to their dynamics, presenting degrees of predictability as well as
      stochastic signals. Finally, differences were found among minor and major caste
      of the same (dimorphic) ant species. Our results underscore the potential of RQA
      and RPs in the analysis of complex behavioral patterns, as well as in general
      inferences on animal behavior and other biological phenomena.

PMID- 29016646
TI  - Methotrexate versus cyclophosphamide for remission maintenance in ANCA-associated
      vasculitis: A randomised trial.
AB  - OBJECTIVES: The treatment of anti-neutrophil cytoplasmic antibody (ANCA)
      associated vasculitis (AAV) is based on remission-induction and remission
      maintenance. Methotrexate is a widely used immunosuppressant but only a few
      studies explored its role for maintenance in AAV. This trial investigated the
      efficacy and safety of methotrexate as maintenance therapy for AAV. METHODS: In
      this single-centre, open-label, randomised trial we compared methotrexate and
      cyclophosphamide for maintenance in AAV. We enrolled patients with granulomatosis
      with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic
      granulomatosis with polyangiitis (EGPA), the latter with poor-prognosis factors
      and/or peripheral neuropathy. Remission was induced with cyclophosphamide. At
      remission, the patients were randomised to receive methotrexate or to continue
      with cyclophosphamide for 12 months; after treatment, they were followed for
      another 12 months. The primary end-point was relapse; secondary end-points
      included renal outcomes and treatment-related toxicity. RESULTS: Of the 94
      enrolled patients, 23 were excluded during remission-induction or did not achieve
      remission; the remaining 71 were randomised to cyclophosphamide (n = 33) or
      methotrexate (n = 38). Relapse frequencies at months 12 and 24 after
      randomisation were not different between the two groups (p = 1.00 and 1.00).
      Relapse-free survival was also comparable (log-rank test p = 0.99). No
      differences in relapses were detected between the two treatments when GPA+MPA and
      EGPA were analysed separately. There were no differences in eGFR at months 12 and
      24; proteinuria declined significantly (from diagnosis to month 24) only in the
      cyclophosphamide group (p = 0.0007). No significant differences in adverse event
      frequencies were observed. CONCLUSIONS: MTX may be effective and safe for
      remission-maintenance in AAV. TRIAL REGISTRATION: clinicaltrials.gov NCT00751517.

PMID- 29016647
TI  - A moving fluoroscope to capture tibiofemoral kinematics during complete cycles of
      free level and downhill walking as well as stair descent.
AB  - Videofluoroscopy has been shown to provide essential information in the
      evaluation of the functionality of total knee arthroplasties. However, due to the
      limitation in the field of view, most systems can only assess knee kinematics
      during highly restricted movements. To avoid the limitations of a static image
      intensifier, a moving fluoroscope has been presented as a standalone system that
      allows tracking of the knee during multiple complete cycles of level- and
      downhill-walking, as well as stair descent, in combination with the synchronous
      assessment of ground reaction forces and whole body skin marker measurements.
      Here, we assess the ability of the system to keep the knee in the field of view
      of the image intensifier. By measuring ten total knee arthroplasty subjects, we
      demonstrate that it is possible to maintain the knee to within 1.8 +/- 1.4 cm
      vertically and 4.0 +/- 2.6 cm horizontally of the centre of the intensifier
      throughout full cycles of activities of daily living. Since control of the system
      is based on real-time feedback of a wire sensor, the system is not dependent on
      repeatable gait patterns, but is rather able to capture pathological motion
      patterns with low inter-trial repeatability.

PMID- 29016651
TI  - Soccer-based promotion of voluntary medical male circumcision: A mixed-methods
      feasibility study with secondary students in Uganda.
AB  - The Ugandan government is committed to scaling-up proven HIV prevention
      strategies including safe male circumcision, and innovative strategies are needed
      to increase circumcision uptake. The aim of this study was to assess the
      acceptability and feasibility of implementing a soccer-based intervention ("Make
      The Cut") among schoolboys in a peri-urban district of Uganda. The intervention
      was led by trained, recently circumcised "coaches" who facilitated a 60-minute
      session delivered in schools, including an interactive penalty shoot-out game
      using metaphors for HIV prevention, sharing of the coaches' circumcision story,
      group discussion and ongoing engagement from the coach to facilitate linkage to
      male circumcision. The study took place in four secondary schools in Entebbe sub
      district, Uganda. Acceptability of safe male circumcision was assessed through a
      cross-sectional quantitative survey. The feasibility of implementing the
      intervention was assessed by piloting the intervention in one school, modifying
      it, and implementing the modified version in a second school. Perceptions of the
      intervention were assessed with in-depth interviews with participants. Of the 210
      boys in the cross-sectional survey, 59% reported being circumcised. Findings
      showed high levels of knowledge and generally favourable perceptions of
      circumcision. The initial implementation of Make The Cut resulted in 6/58
      uncircumcised boys (10.3%) becoming circumcised. Changes made included increasing
      engagement with parents and improved liaison with schools regarding the timing of
      the intervention. Following this, uptake improved to 18/69 (26.1%) in the second
      school. In-depth interviews highlighted the important role of family and peer
      support and the coach in facilitating the decision to circumcise. This study
      showed that the modified Make The Cut intervention may be effective to increase
      uptake of safe male circumcision in this population. However, the intervention is
      time-intensive, and further work is needed to assess the cost-effectiveness of
      the intervention conducted at scale.

PMID- 29016652
TI  - Optimal experimental conditions for Welan gum production by support vector
      regression and adaptive genetic algorithm.
AB  - Welan gum is a kind of novel microbial polysaccharide, which is widely produced
      during the process of microbial growth and metabolism in different external
      conditions. Welan gum can be used as the thickener, suspending agent, emulsifier,
      stabilizer, lubricant, film-forming agent and adhesive usage in agriculture. In
      recent years, finding optimal experimental conditions to maximize the production
      is paid growing attentions. In this work, a hybrid computational method is
      proposed to optimize experimental conditions for producing Welan gum with data
      collected from experiments records. Support Vector Regression (SVR) is used to
      model the relationship between Welan gum production and experimental conditions,
      and then adaptive Genetic Algorithm (AGA, for short) is applied to search
      optimized experimental conditions. As results, a mathematic model of predicting
      production of Welan gum from experimental conditions is obtained, which achieves
      accuracy rate 88.36%. As well, a class of optimized experimental conditions is
      predicted for producing Welan gum 31.65g/L. Comparing the best result in chemical
      experiment 30.63g/L, the predicted production improves it by 3.3%. The results
      provide potential optimal experimental conditions to improve the production of
      Welan gum.

PMID- 29016649
TI  - Small heterodimer partner (SHP) deficiency protects myocardia from lipid
      accumulation in high fat diet-fed mice.
AB  - The small heterodimer partner (SHP) regulates fatty acid oxidation and
      lipogenesis in the liver by regulating peroxisome proliferator-activated receptor
      (PPAR) gamma expression. SHP is also abundantly expressed in the myocardium. We
      investigated the effect of SHP expression on myocardia assessing not only heart
      structure and function but also lipid metabolism and related gene expression in a
      SHP deletion animal model. Transcriptional profiling with a microarray revealed
      that genes participating in cell growth, cytokine signalling, phospholipid
      metabolism, and extracellular matrix are up-regulated in the myocardia of SHP
      knockout (KO) mice compared to those of wild-type (WT) mice (nominal p value <
      0.05). Consistent with these gene expression changes, the left ventricular masses
      of SHP KO mice were significantly higher than WT mice (76.8 +/- 20.5 mg vs. 52.8
      +/- 6.8 mg, P = 0.0093). After 12 weeks of high fat diet (HFD), SHP KO mice
      gained less weight and exhibited less elevation in serum-free fatty acid and less
      ectopic lipid accumulation in the myocardium than WT mice. According to
      microarray analysis, genes regulated by PPARgamma1 and PPARalpha were down
      regulated in myocardia of SHP KO mice compared to their expression in WT mice
      after HFD, suggesting that the reduction in lipid accumulation in the myocardium
      resulted from a decrease in lipogenesis regulated by PPARgamma. We confirmed the
      reduced expression of PPARgamma1 and PPARalpha target genes such as CD36, medium
      chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, and very long
      chain acyl-CoA dehydrogenase by SHP KO after HFD.

PMID- 29016650
TI  - Protein-protein interactions in paralogues: Electrostatics modulates specificity
      on a conserved steric scaffold.
AB  - An improved knowledge of protein-protein interactions is essential for better
      understanding of metabolic and signaling networks, and cellular function.
      Progress tends to be based on structure determination and predictions using known
      structures, along with computational methods based on evolutionary information or
      detailed atomistic descriptions. We hypothesized that for the case of
      interactions across a common interface, between proteins from a pair of paralogue
      families or within a family of paralogues, a relatively simple interface
      description could distinguish between binding and non-binding pairs. Using
      binding data for several systems, and large-scale comparative modeling based on
      known template complex structures, it is found that charge-charge interactions
      (for groups bearing net charge) are generally a better discriminant than buried
      non-polar surface. This is particularly the case for paralogue families that are
      less divergent, with more reliable comparative modeling. We suggest that
      electrostatic interactions are major determinants of specificity in such systems,
      an observation that could be used to predict binding partners.

PMID- 29016653
TI  - Randomized trial of two doses of vitamin D3 in preterm infants <32 weeks: Dose
      impact on achieving desired serum 25(OH)D3 in a NICU population.
AB  - BACKGROUND: Recommendations for vitamin D supplementation for preterm infants
      span a wide range of doses. Response to vitamin D supplementation and impact on
      outcomes in preterm infants is not well understood. OBJECTIVE: Evaluate serum
      25(OH)D3 concentration changes after 4 weeks in response to two different doses
      of vitamin D3 supplementation in a population of premature infants and quantify
      the impact on NICU outcomes. DESIGN: 32 infants born at 24-32 weeks gestation
      were prospectively randomized to receive 400 or 800 IU/day vitamin D3
      supplementation. Serum 25(OH)D3 levels were measured every 4 weeks. The Wilcoxon
      signed rank test was used to compare serum levels of 25(OH)D3 at 4 weeks and each
      subsequent time point. A p-value of <0.05 was considered statistically
      significant. RESULTS: Serum 25(OH)D3 levels at birth were 41.9 and 42.9 nmol/l
      for infants in the 400 IU group and 800 IU group, respectively (p = 0.86). Cord
      25(OH)D3 concentrations significantly correlated with gestational age (r = 0.40,
      p = 0.04). After 4 weeks of D3 supplementation, median 25(OH)D3 levels increased
      in both groups (84.6vs. 105.3 nmol/l for 400 vs. 800 IU/day respectively, with
      significantly more improvement in the higher dose (p = 0.048). Infants in the 400
      IU group were significantly more likely to have dual energy x-ray absorptiometry
      (DEXA) bone density measurements <10 percentile (56% vs 16%, p = 0.04).
      CONCLUSIONS: Improvement in 25(OH)D3 levels at 4 weeks, bone density, and trends
      towards improvement in linear growth support consideration of a daily dose of 800
      IU of vitamin D for infants <32 weeks cared for in the NICU.

PMID- 29016654
TI  - Proton beam irradiation inhibits the migration of melanoma cells.
AB  - PURPOSE: In recent years experimental data have indicated that low-energy proton
      beam radiation might induce a difference in cellular migration in comparison to
      photons. We therefore set out to compare the effect of proton beam irradiation
      and X-rays on the survival and long-term migratory properties of two cell lines:
      uveal melanoma Mel270 and skin melanoma BLM. MATERIALS AND METHODS: Cells treated
      with either proton beam or X-rays were analyzed for their survival using
      clonogenic assay and MTT test. Long-term migratory properties were assessed with
      time-lapse monitoring of individual cell movements, wound test and transpore
      migration, while the expression of the related proteins was measured with western
      blot. RESULTS: Exposure to proton beam and X-rays led to similar survival but the
      quality of the cell colonies was markedly different. More paraclones with a low
      proliferative activity and fewer highly-proliferative holoclones were found after
      proton beam irradiation in comparison to X-rays. At 20 or 40 days post
      irradiation, migratory capacity was decreased more by proton beam than by X-rays.
      The beta-1-integrin level was decreased in Mel270 cells after both types of
      radiation, while vimentin, a marker of EMT, was increased in BLM cells only.
      CONCLUSIONS: We conclude that proton beam irradiation induced long-term
      inhibition of cellular motility, as well as changes in the level of beta-1
      integrin and vimentin. If confirmed, the change in the quality, but not in the
      number of colonies after proton beam irradiation might favor tumor growth
      inhibition after fractionated proton therapy.

PMID- 29016655
TI  - Meta-analysis of peripheral blood gene expression modules for COPD phenotypes.
AB  - Chronic obstructive pulmonary disease (COPD) occurs typically in current or
      former smokers, but only a minority of people with smoking history develops the
      disease. Besides environmental factors, genetics is an important risk factor for
      COPD. However, the relationship between genetics, environment and phenotypes is
      not well understood. Sample sizes for genome-wide expression studies based on
      lung tissue have been small due to the invasive nature of sample collection.
      Increasing evidence for the systemic nature of the disease makes blood a good
      alternative source to study the disease, but there have also been few large-scale
      blood genomic studies in COPD. Due to the complexity and heterogeneity of COPD,
      examining groups of interacting genes may have more relevance than identifying
      individual genes. Therefore, we used Weighted Gene Co-expression Network Analysis
      to find groups of genes (modules) that are highly connected. However, module
      definitions may vary between individual data sets. To alleviate this problem, we
      used a consensus module definition based on two cohorts, COPDGene and ECLIPSE. We
      studied the relationship between the consensus modules and COPD phenotypes
      airflow obstruction and emphysema. We also used these consensus module
      definitions on an independent cohort (TESRA) and performed a meta analysis
      involving all data sets. We found several modules that are associated with COPD
      phenotypes, are enriched in functional categories and are overrepresented for
      cell-type specific genes. Of the 14 consensus modules, three were strongly
      associated with airflow obstruction (meta p <= 0.0002), and two had some
      association with emphysema (meta p <= 0.06); some associations were stronger in
      the case-control cohorts, and others in the cases-only subcohorts. Gene Ontology
      terms that were overrepresented included "immune response" and "defense
      response." The cell types whose type-specific genes were overrepresented in
      modules (p < 0.05) included natural killer cells, dendritic cells, and
      neutrophils. Together, this is the largest investigation of gene blood expression
      in COPD with 469 cases in COPDGene, ECLIPSE and TESRA combined, with 6267 genes
      common to all data sets. Additional, we have 42 and 83 controls in COPDGene and
      ECLIPSE, respectively.

PMID- 29016656
TI  - Behavioral testing of minipigs transgenic for the Huntington gene-A three-year
      observational study.
AB  - BACKGROUND: Large animal models of Huntington's disease (HD) may increase the
      reliability of translating preclinical findings to humans. Long live expectancy
      offers opportunities particularly for disease modifying approaches, but also
      challenges. The transgenic (tg) HD minipig model assessed in this study exhibits
      a high genetic homology with humans, similar body weight, and comparable brain
      structures. To test long-term safety, tolerability, and efficacy of novel
      therapeutic approaches in this model reliable assessments applicable
      longitudinally for several years are warranted for all phenotypical domains
      relevant in HD. OBJECTIVE: To investigate whether the tests proposed assessing
      motor, cognitive and behavioral domains can be applied repetitively over a 3-year
      period in minipigs with acceptable variability or learning effects and whether
      tgHD minipigs reveal changes in these domains compared to wildtype (wt) minipigs
      suggesting the development of an HD phenotype. METHODS: A cohort of 14 tgHD and
      18 wt minipigs was followed for three years. Tests applied every six months
      included a tongue coordination and hurdle test for the motor domain, a color
      discrimination test for cognition, and a dominance test for assessing behavior.
      Statistical analyses were performed using repeated ANOVA for longitudinal group
      comparisons and Wilcoxon-tests for intra-visit differences between tgHD and wt
      minipigs. RESULTS: All tests applied demonstrated feasibility, acceptable
      variance and good consistency during the three-year period. No significant
      differences between tgHD and wt minipigs were detected suggesting lack of a
      phenotype before the age of four years. CONCLUSIONS: The assessment battery
      presented offers measures in all domains relevant for HD and can be applied in
      long-term phenotyping studies with tgHD minipigs. The observation of this cohort
      should be continued to explore the timeline of phenotype development and provide
      information for future interventional studies.

PMID- 29016660
TI  - Correction: Prognostic power of global 2D strain according to left ventricular
      ejection fraction in patients with ST elevation myocardial infarction.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0174160.].

PMID- 29016659
TI  - Effectiveness of longitudinal faculty development programs on MCQs items writing
      skills: A follow-up study.
AB  - This study examines the long-term impact of the faculty development programs on
      the multiple choice question (MCQ) items' quality leading to study its effect on
      the students' overall competency level during their yearly academic assessment. A
      series of longitudinal highly constructed faculty development workshops were
      conducted to improve the quality of the MCQs items writing skills. A total of
      2207 MCQs were constructed by 58 participants for the assessment of 882 students'
      cognitive competency level during the academic years 2012-2015. The MCQs were
      analyzed for the difficulty index (P-value), discriminating index (DI),
      presence/absence of item writing flaws (IWFs), and non-functioning distractors
      (NFDs), Bloom's taxonomy cognitive levels, test reliability, and the rate of
      students' scoring. Significant improvement in the difficulty index and DI were
      noticed during each successive academic year. Easy and poor discriminating
      questions, NFDs and IWFs were decreased significantly, whereas distractor
      efficiency (DE) mean score and high cognitive level (K2) questions were increased
      substantially during the each successive academic year. Improved MCQs' quality
      leaded to increased competency level of the borderline students. Overall, the
      longitudinal faculty development workshops help in improving the quality of the
      MCQs items writing skills of the faculty that leads to students' high competency
      levels.

PMID- 29016657
TI  - Early and late components of EEG delay activity correlate differently with scene
      working memory performance.
AB  - Sustained and elevated activity during the working memory delay period has long
      been considered the primary neural correlate for maintaining information over
      short time intervals. This idea has recently been reinterpreted in light of
      findings generated from multiple neural recording modalities and levels of
      analysis. To further investigate the sustained or transient nature of activity,
      the temporal-spectral evolution (TSE) of delay period activity was examined in
      humans with high density EEG during performance of a Sternberg working memory
      paradigm with a relatively long six second delay and with novel scenes as
      stimuli. Multiple analyses were conducted using different trial window durations
      and different baseline periods for TSE computation. Sensor level analyses
      revealed transient rather than sustained activity during delay periods.
      Specifically, the consistent finding among the analyses was that high amplitude
      activity encompassing the theta range was found early in the first three seconds
      of the delay period. These increases in activity early in the delay period
      correlated positively with subsequent ability to distinguish new from old probe
      scenes. Source level signal estimation implicated a right parietal region of
      transient early delay activity that correlated positively with working memory
      ability. This pattern of results adds to recent evidence that transient rather
      than sustained delay period activity supports visual working memory performance.
      The findings are discussed in relation to synchronous and desynchronous intra-
      and inter-regional neural transmission, and choosing an optimal baseline for
      expressing temporal-spectral delay activity change.

PMID- 29016658
TI  - Probing the interaction between NatA and the ribosome for co-translational
      protein acetylation.
AB  - N-terminal acetylation is among the most abundant protein modifications in
      eukaryotic cells. Over the last decade, significant progress has been made in
      elucidating the function of N-terminal acetylation for a number of diverse
      systems, involved in a wide variety of biological processes. The enzymes
      responsible for the modification are the N-terminal acetyltransferases (NATs).
      The NATs are a highly conserved group of enzymes in eukaryotes, which are
      responsible for acetylating over 80% of the soluble proteome in human cells.
      Importantly, many of these NATs act co-translationally; they interact with the
      ribosome near the exit tunnel and acetylate the nascent protein chain as it is
      being translated. While the structures of many of the NATs have been determined,
      the molecular basis for the interaction with ribosome is not known. Here, using
      purified ribosomes and NatA, a very well-studied NAT, we show that NatA forms a
      stable complex with the ribosome in the absence of other stabilizing factors and
      through two conserved regions; primarily through an N-terminal domain and an
      internal basic helix. These regions may orient the active site of the NatA to
      face the peptide emerging from the exit tunnel. This work provides a framework
      for understanding how NatA and potentially other NATs interact with the ribosome
      for co-translational protein acetylation and sets the foundation for future
      studies to decouple N-terminal acetyltransferase activity from ribosome
      association.

PMID- 29016661
TI  - Modified RNA-seq method for microbial community and diversity analysis using rRNA
      in different types of environmental samples.
AB  - RNA-seq-based SSU (small subunit) rRNA (ribosomal RNA) analysis has provided a
      better understanding of potentially active microbial community within
      environments. However, for RNA-seq library construction, high quantities of
      purified RNA are typically required. We propose a modified RNA-seq method for SSU
      rRNA-based microbial community analysis that depends on the direct ligation of a
      5' adaptor to RNA before reverse-transcription. The method requires only a low
      input quantity of RNA (10-100 ng) and does not require a DNA removal step. The
      method was initially tested on three mock communities synthesized with enriched
      SSU rRNA of archaeal, bacterial and fungal isolates at different ratios, and was
      subsequently used for environmental samples of high or low biomass. For high
      biomass salt-marsh sediments, enriched SSU rRNA and total nucleic acid-derived
      RNA-seq datasets revealed highly consistent community compositions for all of the
      SSU rRNA sequences, and as much as 46.4%-59.5% of 16S rRNA sequences were
      suitable for OTU (operational taxonomic unit)-based community and diversity
      analyses with complete coverage of V1-V2 regions. OTU-based community structures
      for the two datasets were also highly consistent with those determined by all of
      the 16S rRNA reads. For low-biomass samples, total nucleic acid-derived RNA-seq
      datasets were analyzed, and highly active bacterial taxa were also identified by
      the OTU-based method, notably including members of the previously underestimated
      genus Nitrospira and phylum Acidobacteria in tap water, members of the phylum
      Actinobacteria on a shower curtain, and members of the phylum Cyanobacteria on
      leaf surfaces. More than half of the bacterial 16S rRNA sequences covered the
      complete region of primer 8F, and non-coverage rates as high as 38.7% were
      obtained for phylum-unclassified sequences, providing many opportunities to
      identify novel bacterial taxa. This modified RNA-seq method will provide a better
      snapshot of diverse microbial communities, most notably by OTU-based analysis,
      even communities with low-biomass samples.

PMID- 29016662
TI  - Fine mapping of Pi57(t) conferring broad spectrum resistance against Magnaporthe
      oryzae in introgression line IL-E1454 derived from Oryza longistaminata.
AB  - Wild species of the genus Oryza are excellent gene pools for improvement of
      agronomic traits of Asian cultivated rice. The blast resistance gene Pi57(t) in
      the introgression line IL-E1454 derived from Oryza longistaminata was previously
      mapped on rice chromosome 12. Inoculation with 322 Magnaporthe oryzae isolates
      collected from 6 countries indicated that Pi57(t) conferred broad spectrum
      resistance against M. oryzae. Two mapping populations consisting of 29070 and
      10375 F2 plants derived from the crosses of resistant donor IL-E1454 with
      susceptible parents RD23 and Lijiangxintuanheigu respectively, were used for fine
      mapping of Pi57(t) locus. Based on genotyping and phenotyping results of
      recombinants screened from the two crosses, Pi57(t) was finally mapped to a 51.7
      kb region flanked by two molecular markers (STS57-320 and STS57-372) on the short
      arm and close to the centromere of chromosome 12. Six candidate resistance genes
      were predicted in the target region according to the reference sequence of
      Nipponbare. These results could facilitate both marker-assisted selection for
      disease-resistant breeding and gene cloning.

PMID- 29016663
TI  - Information sources, awareness and preventive health behaviors in a population at
      risk of Arsenic exposure: The role of gender and social networks.
AB  - The population of Paracatu is at risk of Arsenic (As) exposure associated with
      long-term exploration of the largest open pit gold mine in Brazil. As part of the
      interdisciplinary research "The Paracatu project: Arsenic environmental
      contamination and human health risks assessment in Paracatu-MG", carried out
      between 2011 and 2013, we used data disaggregated by gender to identify the
      sources of As-related information being accessed by inhabitants of Paracatu and
      to examine if access to these sources was correlated to awareness of As health
      effects and adoption of behaviors to reduce risk of As exposure. Semi-structured,
      face-to-face interviews were carried out with 460 participants (294 women and 166
      men) to collect data on respondent's socio-demographic characteristics, use of
      mass media and social communication networks as sources of information on As
      issues, the trustworthiness of these information sources, awareness of As health
      effects, and adoption of behaviors to reduce As exposure. For both men and women,
      interpersonal communication was used and trusted more frequently than mass media
      to obtain information on As. Discussion of As issues occurred preferentially
      among individuals of the same gender and was associated with awareness of As
      health risks. There are marked differences in variables correlated with the
      adoption of behaviors to reduce the risk of As exposure between men and women.
      Discussing As issues with women was associated with adoption of risk-reduction
      practices for both genders. In contrast, men who discuss As issues with other men
      were less likely to adopt As exposure prevention behaviors. Finally, adoption was
      associated with awareness of As health effects for women, but this was not the
      case for men. Policy implications for decision makers, practitioners and
      researchers are discussed, based on concrete examples of how gender-specific
      approaches can effectively guide the formulation and implementation of health
      promotion campaigns and programs.

PMID- 29016664
TI  - Contribution of cell proliferation to axial elongation in the red flour beetle
      Tribolium castaneum.
AB  - Most arthropods generate their posterior bodies by adding segments periodically,
      as the embryo grows, from a posteriorly located region called the segment
      addition zone. This mode of segmentation is shared with vertebrates and relies on
      oscillatory mechanisms, where the temporal periodicity of a clock is translated
      into repetitive spatial patterns. This ordered anterior-to-posterior pattern is
      achieved at the same time as the tissue elongates, opening the question of the
      functional coordination between the mechanisms of segmental patterning and
      posterior growth. The study of these processes in different arthropods has played
      an important role in unravelling some of the molecular mechanisms of segment
      formation. However, the behavior of cells during elongation and how cellular
      processes affect this segmental patterning has been poorly studied. Cell
      proliferation together with cell rearrangements are presumed to be the major
      forces driving axis elongation in the red flour beetle Tribolium castaneum.
      However, there still no strong evidence about the role and distribution of cell
      proliferation within the embryo. In this study, we propose to address these
      questions by using whole embryo cultures and pharmacological manipulation. We
      show that considerable cell proliferation occurs during germband elongation,
      measured by incorporation of the nucleoside analog of thymidine 5-Ethynyl-2'
      deoxyuridine, EdU. Moreover, proliferating cells appeared to be spread along the
      elongating embryo with a posterior bias at early segmentation. In addition, when
      we blocked cell division, treated germbands were always shorter than controls and
      in some cases not able to fully elongate, even when control embryos already
      started to retract and leg buds are evident. Finally, we found that the absence
      of cell proliferation has no apparent effect on segmental patterning, as
      evidenced by Tc-engrailed (Tc-en) gene expression.

PMID- 29016665
TI  - QTL mapping for flowering-time and photoperiod insensitivity of cotton Gossypium
      darwinii Watt.
AB  - Most wild and semi-wild species of the genus Gossypium are exhibit photoperiod
      sensitive flowering. The wild germplasm cotton is a valuable source of genes for
      genetic improvement of modern cotton cultivars. A bi-parental cotton population
      segregating for photoperiodic flowering was developed by crossing a photoperiod
      insensitive irradiation mutant line with its pre-mutagenesis photoperiodic wild
      type G. darwinii Watt genotype. Individuals from the F2 and F3 generations were
      grown with their parental lines and F1 hybrid progeny in the long day and short
      night summer condition (natural day-length) of Uzbekistan to evaluate photoperiod
      sensitivity, i.e., flowering-time during the seasons 2008-2009. Through
      genotyping the individuals of this bi-parental population segregating for
      flowering-time, linkage maps were constructed using 212 simple-sequence repeat
      (SSR) and three cleaved amplified polymorphic sequence (CAPS) markers. Six QTLs
      directly associated with flowering-time and photoperiodic flowering were
      discovered in the F2 population, whereas eight QTLs were identified in the F3
      population. Two QTLs controlling photoperiodic flowering and duration of
      flowering were common in both populations. In silico annotations of the flanking
      DNA sequences of mapped SSRs from sequenced cotton (G. hirsutum L.) genome
      database has identified several potential 'candidate' genes that are known to be
      associated with regulation of flowering characteristics of plants. The outcome of
      this research will expand our understanding of the genetic and molecular
      mechanisms of photoperiodic flowering. Identified markers should be useful for
      marker-assisted selection in cotton breeding to improve early flowering
      characteristics.

PMID- 29016667
TI  - The transcriptomes of cave and surface populations of Gammarus minus (Crustacea:
      Amphipoda) provide evidence for positive selection on cave downregulated
      transcripts.
AB  - Gammarus minus, a freshwater amphipod living in the cave and surface streams in
      the eastern USA, is an excellent model for investigating evolutionary adaptation
      to the subterranean environment. RNA-Seq was conducted on one pair of
      morphologically distinct sister populations inhabiting surface and cave habitats
      to identify genes that were differentially expressed in the two populations, as
      well as to compare levels and patterns of genetic variation within and between
      populations. Of the 104,630 transcripts identified in the transcriptome assembly,
      57% had higher average levels of expression in the cave population. After
      Benjamini-Hochberg correction for multiple tests, 1517 and 551 transcripts were
      significantly upregulated or downregulated, respectively, in the cave population,
      indicating an almost three-fold enrichment of cave-upregulated genes. The average
      level of nucleotide diversity across all transcripts was significantly lower in
      the cave population. Within the cave population, where the average nucleotide
      diversity of cave-downregulated transcripts was 75% that of the cave-upregulated
      transcripts, a highly significant difference, whereas within the spring
      population the nucleotide diversities of cave-downregulated and cave-upregulated
      transcripts was virtually identical. Three lines of evidence suggest that the
      reduced variation in cave downregulated transcripts is due to positive selection
      in the cave population: 1) the average neutrality index of cave-downregulated
      genes was < 1, consistent with positive selection, and significantly less than
      that of cave-upregulated genes; 2) Tajima's D was positively correlated with the
      cave:surface expression ratio, and 3) cave-downregulated transcripts were
      significantly more likely to be highly diverged from their surface homologs than
      cave-upregulated transcripts. Five transcripts had fixed premature termination
      codons in the cave population. The expression patterns and sequence variation in
      one such transcript, encoding the DNA repair protein photolyase, were examined in
      more detail and provide the first evidence for the relaxation of functional
      constraint in this light-dependent protein in a subterranean population.

PMID- 29016666
TI  - Novel genes and mutations in patients affected by recurrent pregnancy loss.
AB  - Recurrent pregnancy loss is a frequently occurring human infertility-related
      disease affecting ~1% of women. It has been estimated that the cause remains
      unexplained in >50% cases which strongly suggests that genetic factors may
      contribute towards the phenotype. Concerning its molecular aetiology numerous
      studies have had limited success in identifying the disease's genetic causes.
      This might have been due to the fact that hundreds of genes are involved in each
      physiological step necessary for guaranteeing reproductive success in mammals. In
      such scenario, next generation sequencing provides a potentially interesting tool
      for research into recurrent pregnancy loss causative mutations. The present study
      involved whole-exome sequencing and an innovative bioinformatics analysis, for
      the first time, in 49 unrelated women affected by recurrent pregnancy loss. We
      identified 27 coding variants (22 genes) potentially related to the phenotype
      (41% of patients). The affected genes, which were enriched by potentially
      deleterious sequence variants, belonged to distinct molecular cascades playing
      key roles in implantation/pregnancy biology. Using a quantum chemical approach
      method we established that mutations in MMP-10 and FGA proteins led to
      substantial energetic modifications suggesting an impact on their functions
      and/or stability. The next generation sequencing and bioinformatics approaches
      presented here represent an efficient way to find mutations, having potentially
      moderate/strong functional effects, associated with recurrent pregnancy loss
      aetiology. We consider that some of these variants (and genes) represent probable
      future biomarkers for recurrent pregnancy loss.

PMID- 29016668
TI  - Diversity of clinical isolates of Aspergillus terreus in antifungal
      susceptibilities, genotypes and virulence in Galleria mellonella model:
      Comparison between respiratory and ear isolates.
AB  - We analyzed the antifungal susceptibility profiles, genotypes, and virulence of
      clinical Aspergillus terreus isolates from six university hospitals in South
      Korea. Thirty one isolates of A. terreus, comprising 15 respiratory and 16 ear
      isolates were assessed. Microsatellite genotyping was performed, and genetic
      similarity was assessed by calculating the Jaccard index. Virulence was evaluated
      by Galleria mellonella survival assay. All 31 isolates were susceptible to
      itraconazole, posaconazole, and voriconazole, while 23 (74.2%) and 6 (19.4%)
      showed amphotericin B (AMB) minimum inhibitory concentrations (MICs) of <= 1 mg/L
      and > 4 mg/L, respectively. Notably, respiratory isolates showed significantly
      higher geometric mean MICs than ear isolates to AMB (2.41 vs. 0.48 mg/L),
      itraconazole (0.40 vs. 0.19 mg/L), posaconazole (0.16 vs. 0.08 mg/L), and
      voriconazole (0.76 vs. 0.31 mg/L) (all, P <0.05). Microsatellite genotyping
      separated the 31 isolates into 27 types, but the dendrogram demonstrated a closer
      genotypic relatedness among isolates from the same body site (ear or respiratory
      tract); in particular, the majority of ear isolates clustered together.
      Individual isolates varied markedly in their ability to kill infected G.
      mellonella after 72 h, but virulence did not show significant differences
      according to source (ear or respiratory tract), genotype, or antifungal
      susceptibility. The current study shows the marked diversity of clinical isolates
      of A. terreus in terms of antifungal susceptibilities, genotypes and virulence in
      the G. mellonella model, and ear isolates from Korean hospitals may have lower
      AMB or triazole MICs than respiratory isolates.

PMID- 29016669
TI  - Major depressive disorder and suicide risk among adult outpatients at several
      general hospitals in a Chinese Han population.
AB  - BACKGROUND: Somatic complaints are often the presenting symptoms of major
      depressive disorder (MDD) in the outpatient context, because this may go
      unrecognized. It is well understood that MDD carries an increased risk of
      suicide. This study aimed to identify the risk factors and association with both
      MDD and suicidality among Han Chinese outpatients. METHODS: A multicenter study
      was carried out in 5189 outpatient adults (>=18 years old) in four general
      hospitals in Guangzhou, China. The 1392 patients who had the Patient Health
      Questionnaire-9 (PHQ-9) score >= 5, indicating depressive symptoms were offered
      an interview with a psychiatrist by the Mini International Neuropsychiatric
      Interview (MINI); 819 patients consented and completed the MINI interview. MINI
      module B was used to assess suicidality. Stepwise binary logistic models were
      used to estimate the relationship between a significant risk factor and suicide
      or MDD. According to with or without MDD, the secondary analysis was performed
      using the logistic regression model for the risk of suicidility. RESULTS: The
      current prevalence of MDD and the one month prevalence of suicidality were 3.7%
      and 2.3% respectively. The odds ratio of suicidality in women was more than twice
      that in men (OR = 2.62; 95% CI 1.45-4.76). Other risk factors which were
      significantly associated with suicidality were: living alone, higher education,
      self-reported depression, getting psychiatric diagnoses (MDD, anxiety disorders,
      and bipolar disorders). Significant risk factors for MDD were also noticed, such
      as comorbid anxiety disorders, self-reported anxiety, insomnia, suicidal
      ideation. LIMITATION: It's a cross-sectional study in outpatient clinics using
      self-report questionnaires. CONCLUSION: This study provides valuable data about
      the risk factors and association of MDD and suicide risk in adult outpatients in
      Han Chinese. Those factors allow better the employment of preventative measures.

PMID- 29016670
TI  - A novel function of N-linked glycoproteins, alpha-2-HS-glycoprotein and
      hemopexin: Implications for small molecule compound-mediated neuroprotection.
AB  - Therapeutic agents to the central nervous system (CNS) need to be efficiently
      delivered to the target site of action at appropriate therapeutic levels.
      However, a limited number of effective drugs for the treatment of neurological
      diseases has been developed thus far. Further, the pharmacological mechanisms by
      which such therapeutic agents can protect neurons from cell death have not been
      fully understood. We have previously reported the novel small-molecule compound,
      2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide
      trihydrochloride (WN1316), as a unique neuroprotectant against oxidative injury
      and a highly promising remedy for the treatment of amyotrophic lateral sclerosis
      (ALS). One of the remarkable characteristics of WN1316 is that its efficacious
      doses in ALS mouse models are much less than those against oxidative injury in
      cultured human neuronal cells. It is also noted that the WN1316 cytoprotective
      activity observed in cultured cells is totally dependent upon the addition of
      fetal bovine serum in culture medium. These findings led us to postulate some
      serum factors being tightly linked to the WN1316 efficacy. In this study, we
      sieved through fetal bovine serum proteins and identified two N-linked
      glycoproteins, alpha-2-HS-glycoprotein (AHSG) and hemopexin (HPX), requisites to
      exert the WN1316 cytoprotective activity against oxidative injury in neuronal
      cells in vitro. Notably, the removal of glycan chains from these molecules did
      not affect the WN1316 cytoprotective activity. Thus, two glycoproteins, AHSG and
      HPX, represent a pivotal glycoprotein of the cytoprotective activity for WN1316,
      showing a concrete evidence for the novel glycan-independent function of serum
      glycoproteins in neuroprotective drug efficacy.

PMID- 29016671
TI  - Prognostic and clinicopathological value of Twist expression in breast cancer: A
      meta-analysis.
AB  - BACKGROUND: Despite initial indications that the transcription factor Twist could
      be used as a breast cancer prognostic marker, there still exists some controversy
      about its reliability. Thus, the aim of the present study was to assess the
      relationship between Twist expression and prognosis in breast carcinoma.
      MATERIALS AND METHODS: We identified eligible studies that reported an
      association between Twist expression and breast cancer prognosis by searching the
      literature in PubMed, Embase, the Cochrane Library, and Web of Science databases,
      through June 5, 2017. Studies investigating Twist protein or mRNA expression as
      well as reporting survival data in breast cancer were included. The pooled hazard
      ratio (HR) and odds radio (OR) with a 95% confidence interval (95% CI) were used
      to estimate associations. RESULTS: A total of 2,671 patients from seven included
      studies were assessed, and the data indicated that increased Twist expression
      significantly correlated with poor overall survival (OS) (HR, 1.15; 95% CI, 1.00
      1.33; P = 0.04) in breast cancer. In addition, we also observed a significant
      correlation of elevated Twist expression with larger tumor size (OR, 1.92; 95%
      CI, 1.31-2.81; P = 0.0009), lymph node involvement (OR, 3.81; 95% CI, 1.16-12.54;
      P = 0.03), higher nuclear grade (OR, 1.45; 95% CI, 1.06-2.00; P = 0.02), and
      positive human epidermal growth factor receptor 2 (HER2) status (OR, 1.49; 95%
      CI, 1.06-2.09; P = 0.02). However, no correlation between Twist expression and
      disease-free survival (DFS), age, estrogen receptor (ER) status, and progesterone
      receptor (PR) status was observed. CONCLUSIONS: Our results demonstrate that
      Twist over-expression is a statistically significant indicator of OS in breast
      cancer. In addition, our meta-analysis shows that increased Twist expression is
      significantly associated with larger tumor size, lymph node involvement, higher
      nuclear grade, and positive HER2 status.

PMID- 29016672
TI  - The interaction of arsenic and N-butyl-N-(4-hydroxybutyl)nitrosamine on
      urothelial carcinogenesis in mice.
AB  - The bladder is an important organ for the storage of excreted water and
      metabolites. If metabolites with carcinogenic characteristics are present in
      urine, the urothelial lining of the bladder could be damaged and genetically
      altered. In this study, we analyzed the interaction of arsenic and N-butyl-N-(4
      hydroxybutyl)nitrosamine (BBN) on mouse bladder carcinogenesis. Our previous
      study found that arsenic affects BBN-altered urothelial enzymatic activity,
      protein expression, DNA oxidation and global DNA CpG methylation levels. In this
      study, two mouse models were used. First, after administering a co-treatment of
      BBN and arsenic for 20 weeks, BBN alone led to a urothelial carcinoma formation
      of 20%, and arsenic promoted a BBN-induced urothelial carcinoma formation of 10%.
      The protein expression of GSTM1, GSTO1, NQO1, and p21 did not change by arsenic
      along with the BBN co-treatment, but the Sp1 expression increased. In the second
      mouse model, BBN was a pretreatment promoter; arsenic dose-dependently
      deteriorated BBN-promoted dysplasia by 10% and 40% at 10 ppm and 100 ppm,
      respectively. Conversely, BBN pretreatment also accelerated arsenic-induced
      dysplasia by 30%. The urothelial carcinogenic effect reversed after ceasing BBN
      for a period of 20 weeks. In summary, three conclusions were drawn from this
      study. The first is the mutual promotion of arsenic and BBN in bladder
      carcinogenesis. Second, arsenic dosages without bladder carcinogenicity (10 ppm)
      or with slight carcinogenicity (100 ppm) promote BBN-induced mice bladder cancer
      progression. Finally, the dysplastic urothelium had reverted to near-normal
      morphology after ceasing BBN intake for 20 weeks, providing a good suggestion for
      people who want to quit smoking.

PMID- 29016673
TI  - A systematic review and meta-analysis comparing combined intravenous and topical
      tranexamic acid with intravenous administration alone in THA.
AB  - PURPOSE: To compare the effectiveness and safety of combined intravenous and
      topical tranexamic acid with intravenous use alone in THA. METHODS: The
      electronic databases MEDLINE, EMBASE, BIOSIS, Cochrane central, and further
      adapted for Google and Google Scholar internet, last updated on Dec 30, 2016,
      were searched. Evaluated outcomes included total blood loss, transfusion rate,
      maximum postoperative Hb drop, and incidence of thromboembolic complications. The
      standard mean difference (SMD) or the relative risk (RR) was calculated for
      continuous or dichotomous data respectively. The quality of the trial was
      assessed, and meta-analyses were performed with the Cochrane Collaboration's
      RevMan 5.0 software. RESULTS: Five RCTs with 457 patients were included. Combined
      TXA administration reduced blood loss (SMD, 1.39; 95%CI, 0.55 to 2.23; P<0.00001,
      I2 = 94%), hemoglobin decline (SMD, 0.84; 95%CI, 0.13 to 1.54; P = 0.01, I2 =
      83%) and the need for transfusion (RR, 2.58; 95%CI, 1.59 to 4.18; P = 0.65, I2 =
      0%) without increasing the rate of thromboembolic complications significantly
      (RR, 0.83; 95%CI, 0.27 to 2.54; P = 0.81, I2 = 0%). CONCLUSION: The present study
      has emphasized that combined TXA administration can effectively reduce blood
      loss, hemoglobin decline and the need for transfusion without increasing the rate
      of thromboembolic complications.

PMID- 29016674
TI  - Re-evaluation of IL-10 signaling reveals novel insights on the contribution of
      the intracellular domain of the IL-10R2 chain.
AB  - Interleukin-10 (IL-10) is an anti-inflammatory cytokine that plays a key role in
      maintaining immune homeostasis. IL-10-mediated responses are triggered upon
      binding to a heterodimeric receptor complex consisting of IL-10 receptor (IL
      10R)1 and IL-10R2. Engagement of the IL-10R complex activates the intracellular
      kinases Jak1 and Tyk2, but the exact roles of IL-10R2 and IL-10R2-associated
      signaling via Tyk2 remain unclear. To elucidate the contribution of IL-10R2 and
      its signaling to IL-10 activity, we re-evaluated IL-10-mediated responses on bone
      marrow-derived dendritic cells, macrophages and mast cells. By using bone marrow
      from IL-10R-/- mice it was revealed that IL-10-mediated responses depend on both
      IL-10R1 and IL-10R2 in all three cell types. On the contrary, bone marrow-derived
      cells from Tyk2-/- mice showed similar responses to IL-10 as wild-type cells,
      indicating that signaling via this IL-10R2-associated kinase only plays a limited
      role. Tyk2 was shown to control the amplitude of STAT3 activation and the up
      regulation of downstream SOCS3 expression. SOCS3 up-regulation was found to be
      cell-type dependent and correlated with the lack of early suppression of LPS
      induced TNF-alpha in dendritic cells. Further investigation of the IL-10R complex
      revealed that both the extracellular and intracellular domains of IL-10R2
      influence the conformation of IL-10R1 and that both domains were required for
      transducing IL-10 signals. This observation highlights a novel role for the
      intracellular domain of IL-10R2 in the molecular mechanisms of IL-10R activation.

PMID- 29016675
TI  - Effect of small-sided team sport training and protein intake on muscle mass,
      physical function and markers of health in older untrained adults: A randomized
      trial.
AB  - : The effect of small-sided team sport training and protein intake on muscle
      mass, physical function, and adaptations important for health in untrained older
      adults was examined. Forty-eight untrained older (72+/-6 (+/-standard deviation,
      SD) years men and women were divided into either a team sport group ingesting a
      drink high in protein (18 g) immediately and 3 h after each training session (TS
      HP, n = 13), a team sport group ingesting an isocaloric drink with low protein
      content (3 g; TS-LP, n = 18), or a control group continuing their normal
      activities (CON, n = 17). The team sport training was performed as ~20 min of
      small-sided ball games twice a week over 12 weeks. After the intervention period,
      leg muscle mass was 0.6 kg higher (P = 0.047) in TS-HP, with no effect in TS-LP.
      In TS-HP, number of sit-to-stand repetitions increased (1.2+/-0.6, P = 0.054),
      time to perform 2.45 m up-and-go was lower (0.7+/-0.3 s, P = 0.03) and number of
      arm curl repetitions increased (3.5+/-1.2, P = 0.01), whereas in TS-LP only
      number of repetitions in sit-to-stand was higher (1.6+/-0.6, P = 0.01). In TS-LP,
      reductions were observed in total and abdominal fat mass (1.2+/-0.5 and 0.4+/-0.2
      kg, P = 0.03 and P = 0.02, respectively), heart rate at rest (9+/-3 bpm, P =
      0.002) and plasma C-reactive protein (1.8+/-0.8 mmol/L, P = 0.03), with no
      effects in TS-HP. Thus, team sport training improves functional capacity of
      untrained older adults and increases leg muscle mass only when ingesting proteins
      after training. Furthermore, team sport training followed by intake of drink with
      low protein content does lower fat mass, heart rate at rest and level of systemic
      inflammation. TRIAL REGISTRATION: clinicaltrials.gov NCT03120143.

PMID- 29016676
TI  - Long-term dynamics of Mycoplasma conjunctivae at the wildlife-livestock interface
      in the Pyrenees.
AB  - Functional roles of domestic and wild host populations in infectious
      keratoconjunctivitis (IKC) epidemiology have been extensively discussed claiming
      a domestic reservoir for the more susceptible wild hosts, however, based on
      limited data. With the aim to better assess IKC epidemiology in complex host
      pathogen alpine systems, the long-term infectious dynamics and molecular
      epidemiology of Mycoplasma conjunctivae was investigated in all host populations
      from six study areas in the Pyrenees and one in the Cantabrian Mountains
      (Northern Spain). Detection of M. conjunctivae was performed by qPCR on 3600 eye
      swabs collected during seven years from hunted wild ungulates and sympatric
      domestic sheep (n = 1800 animals), and cluster analyses of the strains were
      performed including previous reported local strains. Mycoplasma conjunctivae was
      consistently detected in three Pyrenean chamois (Rupicapra p. pyrenaica)
      populations, as well as in sheep flocks (17.0% of sheep) and occasionally in
      mouflon (Ovis aries musimon) from the Pyrenees (22.2% in one year/area);
      statistically associated with ocular clinical signs only in chamois. Chamois
      populations showed different infection dynamics with low but steady prevalence
      (4.9%) and significant yearly fluctuations (0.0%- 40.0%). Persistence of specific
      M. conjunctivae strain clusters in wild host populations is demonstrated for six
      and nine years. Cross-species transmission between chamois and sheep and chamois
      and mouflon were also sporadically evidenced. Overall, independent M.
      conjunctivae sylvatic and domestic cycles occurred at the wildlife-livestock
      interface in the alpine ecosystems from the Pyrenees with sheep and chamois as
      the key host species for each cycle, and mouflon as a spill-over host. Host
      population characteristics and M. conjunctivae strains resulted in different
      epidemiological scenarios in chamois, ranging from the fading out of the
      mycoplasma to the epidemic and endemic long-term persistence. These findings
      highlight the capacity of M. conjunctivae to establish diverse interactions and
      persist in host populations, also with different transmission conditions.

PMID- 29016677
TI  - Study on the presence of ochratoxin alpha in cultures of ochratoxigenic and non-
      ochratoxigenic strains of Aspergillus carbonarius.
AB  - Ochratoxin A (OTA) is a potent nephrotoxin and carcinogen which is found in a
      wide variety of common foods and beverages and it is produced by several species
      of Aspergillus and Penicillium. Ochratoxin alpha (OTalpha), a major metabolite of
      OTA, has also been reported to occur in cultures of OTA-producing species.
      However there is some controversial about the participation of OTalpha in the
      biosynthesis of OTA, mainly because its biosynthesis pathway has not yet been
      completely characterized. Aspergillus carbonarius is the main responsible source
      of ochratoxin A (OTA) in food commodities such as wine, grapes or dried vine
      fruits from main viticultural regions worldwide. However, little is known about
      the presence of OTalpha in isolates of A. carbonarius. In this study we evaluated
      the effects of temperature and incubation time on OTalpha production by both OTA
      and non-OTA-producing strains of A. carbonarius. OTA and OTalpha were detected on
      the basis of HPLC fluorometric response compared with that of their standards and
      confirmed by HPLC-MS in selected samples. The non-OTA-producing strains did
      produce neither OTA nor OTalpha at any of the conditions tested. The OTA
      producing strains studied were able to produce both OTA and OTalpha in most of
      the conditions tested. In general, higher amounts of OTA than OTalpha were
      produced, but a positive correlation in the production of these two metabolites
      was detected. The lack of production of both OTA and OTalpha in the non-OTA
      producing strains could be caused by the presence of silent genes or by mutations
      in functional or regulatory genes involved in OTA production.

PMID- 29016678
TI  - Can editors save peer review from peer reviewers?
AB  - Peer review is the gold standard for scientific communication, but its ability to
      guarantee the quality of published research remains difficult to verify. Recent
      modeling studies suggest that peer review is sensitive to reviewer misbehavior,
      and it has been claimed that referees who sabotage work they perceive as
      competition may severely undermine the quality of publications. Here we examine
      which aspects of suboptimal reviewing practices most strongly impact quality, and
      test different mitigating strategies that editors may employ to counter them. We
      find that the biggest hazard to the quality of published literature is not
      selfish rejection of high-quality manuscripts but indifferent acceptance of low
      quality ones. Bypassing or blacklisting bad reviewers and consulting additional
      reviewers to settle disagreements can reduce but not eliminate the impact. The
      other editorial strategies we tested do not significantly improve quality, but
      pairing manuscripts to reviewers unlikely to selfishly reject them and allowing
      revision of rejected manuscripts minimize rejection of above-average manuscripts.
      In its current form, peer review offers few incentives for impartial reviewing
      efforts. Editors can help, but structural changes are more likely to have a
      stronger impact.

PMID- 29016680
TI  - Targeted mutagenesis in a human-parasitic nematode.
AB  - Parasitic nematodes infect over 1 billion people worldwide and cause some of the
      most common neglected tropical diseases. Despite their prevalence, our
      understanding of the biology of parasitic nematodes has been limited by the lack
      of tools for genetic intervention. In particular, it has not yet been possible to
      generate targeted gene disruptions and mutant phenotypes in any parasitic
      nematode. Here, we report the development of a method for introducing CRISPR-Cas9
      mediated gene disruptions in the human-parasitic threadworm Strongyloides
      stercoralis. We disrupted the S. stercoralis twitchin gene unc-22, resulting in
      nematodes with severe motility defects. Ss-unc-22 mutations were resolved by
      homology-directed repair when a repair template was provided. Omission of a
      repair template resulted in deletions at the target locus. Ss-unc-22 mutations
      were heritable; we passed Ss-unc-22 mutants through a host and successfully
      recovered mutant progeny. Using a similar approach, we also disrupted the unc-22
      gene of the rat-parasitic nematode Strongyloides ratti. Our results demonstrate
      the applicability of CRISPR-Cas9 to parasitic nematodes, and thereby enable
      future studies of gene function in these medically relevant but previously
      genetically intractable parasites.

PMID- 29016679
TI  - Perimenopause and emergence of an Alzheimer's bioenergetic phenotype in brain and
      periphery.
AB  - After advanced age, female sex is the major risk factor for Alzheimer's disease
      (AD). The biological mechanisms underlying the increased AD risk in women remain
      largely undetermined. Preclinical studies identified the perimenopause to
      menopause transition, a neuroendocrine transition state unique to the female, as
      a sex-specific risk factor for AD. In animals, estrogenic regulation of cerebral
      glucose metabolism (CMRglc) falters during perimenopause. This is evident in
      glucose hypometabolism and decline in mitochondrial efficiency which is sustained
      thereafter. This study bridges basic to clinical science to characterize brain
      bioenergetics in a cohort of forty-three, 40-60 year-old clinically and
      cognitively normal women at different endocrine transition stages including
      premenopause (controls, CNT, n = 15), perimenopause (PERI, n = 14) and
      postmenopause (MENO, n = 14). All participants received clinical, laboratory and
      neuropsychological examinations, 18F-fluoro-deoxyglucose (FDG)-Positron Emission
      Tomography (PET) FDG-PET scans to estimate CMRglc, and platelet mitochondrial
      cytochrome oxidase (COX) activity measures. Statistical parametric mapping and
      multiple regression models were used to examine clinical, CMRglc and COX data
      across groups. As expected, the MENO group was older than PERI and controls.
      Groups were otherwise comparable for clinical measures and distribution of APOE4
      genotype. Both MENO and PERI groups exhibited reduced CMRglc in AD-vulnerable
      regions which was correlated with decline in mitochondrial COX activity compared
      to CNT (p's<0.001). A gradient in biomarker abnormalities was most pronounced in
      MENO, intermediate in PERI, and lowest in CNT (p<0.001). Biomarkers correlated
      with immediate and delayed memory scores (Pearson's 0.26<=r<=0.32, p<=0.05).
      These findings validate earlier preclinical findings and indicate emergence of
      bioenergetic deficits in perimenopausal and postmenopausal women, suggesting that
      the optimal window of opportunity for therapeutic intervention in women is early
      in the endocrine aging process.

PMID- 29016682
TI  - Effects of mandibular setback with or without maxillary advancement osteotomies
      on pharyngeal airways: An overview of systematic reviews.
AB  - BACKGROUND: Mandibular setback osteotomies potentially lead to narrowing of the
      pharyngeal airways, subsequently resulting in post-surgical obstructive sleep
      apnea (OSA). OBJECTIVE: To summarize current evidence from systematic reviews
      that has evaluated pharyngeal airway changes after mandibular setback with or
      without concomitant upper jaw osteotomies. METHODOLOGY: PubMed, EMBASE, Web of
      Science, and Cochrane Library databases were searched with no restriction of
      language or date. Systematic reviews studying changes in pharyngeal airway
      dimensions and respiratory parameters after mandibular setback with or without
      concomitant upper jaw osteotomies have been identified, screened for eligibility,
      included and analyzed in this study. RESULTS: Six systematic reviews have been
      included. While isolated mandibular setback osteotomies result in reduced
      oropharyngeal airway dimensions, the reduction is lesser in cases with
      concomitant upper jaw osteotomies. Only scarce evidence exists currently to what
      happens to naso- and hypo-pharyngeal airways. There is no evidence for post
      surgical OSA, even though some studies reported reduced respiratory parameters
      after single-jaw mandibular setback with or without concomitant upper jaw
      osteotomies. CONCLUSION: Although mandibular setback osteotomies reduce
      pharyngeal airway dimensions, evidence confirming post-surgical OSA was not
      found. Nevertheless, potential post-surgical OSA should be taken into serious
      consideration during the treatment planning of particular orthognathic cases. As
      moderate evidence exists that double-jaw surgeries lead to less compromised post
      surgical pharyngeal airways, they should be considered as the method of choice
      especially in cases with severe dentoskeletal Class III deformity. STUDY
      REGISTRATION: PROSPERO (registration number: CRD42016046484).

PMID- 29016681
TI  - Heterodimerization of two pore domain K+ channel TASK1 and TALK2 in living
      heterologous expression systems.
AB  - Two-pore-domain K+ (K2P) channels sense a wide variety of stimuli such as
      mechanical stress, inhalational anesthetics, and changes in extracellular pH or
      temperature. The K2P channel activity forms a background K+ current and, thereby,
      contributes to resting membrane potentials. Six subfamilies including fifteen
      subtypes of K2P channels have been identified. Each K2P channel molecule with two
      pores consists of a homodimer of each subtype. In addition, a few heterodimers
      mainly within the same subfamilies have been found recently. In the present
      study, the possibility of heterodimerization between TASK1 (TWIK-Related Acid
      Sensitive K+ channel) and TALK2 (TWIK-Related Alkaline pH-Activated K+ channel)
      was examined. These channels belong to separate subfamilies and show extremely
      different channel properties. Surprisingly, single molecular imaging analyses in
      this study using a total internal reflection microscope suggested the
      heterodimerization of TASK1 and TALK2 in a pancreatic cell line, QGP-1. This
      heterodimer was also detected using a bimolecular fluorescence complementation
      assay in a HEK293 heterologous expression system. Fluorescence resonance energy
      transfer analyses showed that the affinity between TASK1 and TALK2 appeared to be
      close to those of homodimers. Whole-cell patch-clamp recordings revealed that
      TASK1 currents in HEK293 cells were significantly attenuated by co-expression of
      a dominant-negative form of TALK2 in comparison with that of wild-type TALK2. The
      sensitivities of TASK1-TALK2 tandem constructs to extracellular pH and halothane
      were characterized as a unique hybrid of TASK1 and TALK2. These results suggested
      that heterodimerization of TASK1 and TALK2 provides cells with the ability to
      make multiple responses to a variety of physiological and pharmacological
      stimuli.

PMID- 29016683
TI  - The epigenetic factor PCAF regulates vascular inflammation and is essential for
      intimal hyperplasia development.
AB  - OBJECTIVE: Genetic P300/CBP-associated factor (PCAF) variation affects restenosis
      risk in patients. PCAF has lysine acetyltransferase activity and promotes nuclear
      factor kappa-beta (NFkappaB)-mediated inflammation, which drives post
      interventional intimal hyperplasia development. We studied the contributing role
      of PCAF in post-interventional intimal hyperplasia. METHODS AND RESULTS: PCAF
      contribution to inflammation and intimal hyperplasia was assessed in leukocytes,
      macrophages and vascular smooth muscle cells (vSMCs) in vitro and in a mouse
      model for intimal hyperplasia, in which a cuff is placed around the femoral
      artery. PCAF deficiency downregulate CCL2, IL-6 and TNF-alpha expression, as
      demonstrated on cultured vSMCs, leukocytes and macrophages. PCAF KO mice showed a
      71.8% reduction of vSMC-rich intimal hyperplasia, a 73.4% reduction of
      intima/media ratio and a 63.7% reduction of luminal stenosis after femoral artery
      cuff placement compared to wild type (WT) mice. The association of PCAF and
      vascular inflammation was further investigated using the potent natural PCAF
      inhibitor garcinol. Garcinol treatment reduced CCL2 and TNF-alpha expression, as
      demonstrated on cultured vSMCs and leukocytes. To assess the effect of garcinol
      treatment on vascular inflammation we used hypercholesterolemic ApoE*3-Leiden
      mice. After cuff placement, garcinol treatment resulted in reduced arterial
      leukocyte and macrophage adherence and infiltration after three days compared to
      untreated animals. CONCLUSIONS: These results identify a vital role for the
      lysine acetyltransferase PCAF in the regulation of local inflammation after
      arterial injury and likely the subsequent vSMC proliferation, responsible for
      intimal hyperplasia.

PMID- 29016684
TI  - Performance of the Xpert MTB/RIF assay for the diagnosis of pulmonary
      tuberculosis and rifampin resistance in a low-incidence, high-resource setting.
AB  - Performance of the Xpert MTB/RIF assay, designed to simultaneously detect
      Mycobacterium tuberculosis complex (MTBC) and rifampin (RIF) resistance, has been
      well documented in low-resource settings with high TB-incidence. However, few
      studies have assessed its accuracy in low TB incidence settings. We evaluated the
      performance of Xpert MTB/RIF using clinical sputum specimens routinely collected
      from suspect pulmonary TB patients over a 4-year time period in San Diego County,
      California. Xpert MTB/RIF results were compared to acid-fast bacilli (AFB) smear
      microscopy, mycobacterial culture, and phenotypic drug susceptibility testing
      (DST). Of 751 sputum specimens, 134 (17.8%) were MTBC culture-positive and 2
      (1.5%) were multidrug-resistant (MDR). For the detection of MTBC, Xpert MTB/RIF
      sensitivity was 89.6% (97.7% and 74.5% in smear-positive and -negative sputa,
      respectively) and specificity was 97.2%; while AFB smear sensitivity and
      specificity were 64.9% and 77.8%, respectively. Xpert MTB/RIF detected 35 of 47
      smear-negative culture-positive specimens, and excluded 124 of 137 smear-positive
      culture-negative specimens. Xpert MTB/RIF also correctly excluded 99.2% (121/122)
      of nontuberculous mycobacteria (NTM) specimens, including all 33 NTM false
      positives by smear microscopy. For the detection of RIF resistance, Xpert MTB/RIF
      sensitivity and specificity were 100% and 98.3%, respectively. Our findings
      demonstrate that Xpert MTB/RIF is able to accurately detect MTBC and RIF
      resistance in routinely collected respiratory specimens in a low TB-incidence
      setting, with comparable performance to that achieved in high-incidence settings;
      and suggest that under these conditions the assay has particular utility in
      detecting smear-negative TB cases, excluding smear-positive patients without MTBC
      disease, and differentiating MTBC from NTM.

PMID- 29016685
TI  - Lactobacillus rhamnosus PB01 (DSM 14870) supplementation affects markers of sperm
      kinematic parameters in a diet-induced obesity mice model.
AB  - Probiotics have been proposed as alternatives to pharmacological products in
      several medical conditions including the modulation of obesity, which is
      frequently associated with poor semen quality. However, effects of probiotics on
      male fertility have been less investigated. This study assessed the effect of
      Lactobacillus rhamnosus PB01 (DSM-14870) on sperm kinematic parameters in Normal
      weight (NW) and diet-induced obese (DIO) models. NW and DIO C57BL/6NTac mice were
      divided into two subgroups with or without a single daily dose (1x109CFU) of L.
      rhamnosus for four weeks. Sperm motility and kinematics together with blood lipid
      profiles and reproductive hormone levels were assessed using the sperm class
      analyzer system. Probiotic supplementation increased serum testosterone, LH and
      FSH levels in both NW and DIO groups resulting in significantly (P<0.05) higher
      velocity (VSL, VCL and VAP) and percentages of progressively motile sperm and
      significantly lower percentages of immotile sperm. Other kinematic parameters
      (Lin, STR, ALH and BCF) were also increased in both probiotic supplemented DIO
      and NW groups at the 10% level of significance. Probiotic supplemented DIO mice
      demonstrated significantly higher percentages of progressively motile sperm
      versus DIO controls. This study demonstrated the potential of L. rhamnosus PB01
      as a regulatory agent with positive effects on weight loss and reproductive
      hormones, significantly improving sperm motility and kinematic parameters in male
      DIO models.

PMID- 29016687
TI  - Effect of weekend admission on mortality associated with severe acute kidney
      injury in England: A propensity score matched, population-based study.
AB  - BACKGROUND: Increased in-hospital mortality associated with weekend admission has
      been reported for many acute conditions, but no study has investigated "weekend
      effect" for acute kidney injury requiring dialysis (AKI-D). METHODS: In this
      large, propensity score matched cohort of AKI-D, we examined the impact of
      weekend admission and in-centre nephrology services in 53,170 AKI-D admissions
      between 1st April 2003 and 31st March 2015 using a hospital episode statistic
      dataset. Propensity score matching (PSM) was performed to match 4284 weekend
      admissions with AKI-D with 14,788 admissions on weekdays. RESULTS: Of the 53,170
      admissions with AKI-D in the whole dataset, 12,357 (23%) were at weekends. The
      unadjusted mortality for weekend admissions was significantly higher compared to
      admissions on weekdays (40.6% versus 39.6%, p 0.046). However, in multivariable
      analysis of the PSM cohort, the odds of death for weekend admissions with AKI-D
      was 1.01 (95%CI 0.93,1.09). Mortality was higher for weekend admissions in West
      Midlands (odds ratio (OR) 1.32, 95% confidence interval (CI) 1.05, 1.66) and
      lower in East of England (OR 0.77, 95%CI 0.59, 1.00) but was not different to
      weekday admissions in all other regions. In 2003-04, weekend admissions had lower
      odds of death (OR 0.45, 95%CI 0.21, 0.96) and in 2010-11 higher odds of death (OR
      1.28, 95%CI 1.00, 1.63) but in the other ten years observed, there was no
      significant difference in mortality between weekday and weekend admissions.
      Provision of in-centre nephrology services was associated with lower odds of
      death at 0.57 (95%CI 0.54, 0.62). CONCLUSIONS: Weekend admissions in patients
      with AKI-D had no effect on mortality. Further research is warranted to elucidate
      the reasons for the lower mortality in hospitals with in-centre nephrology
      services.

PMID- 29016686
TI  - Learning about learning: Mining human brain sub-network biomarkers from fMRI
      data.
AB  - Modeling the brain as a functional network can reveal the relationship between
      distributed neurophysiological processes and functional interactions between
      brain structures. Existing literature on functional brain networks focuses mainly
      on a battery of network properties in "resting state" employing, for example,
      modularity, clustering, or path length among regions. In contrast, we seek to
      uncover functionally connected subnetworks that predict or correlate with cohort
      differences and are conserved within the subjects within a cohort. We focus on
      differences in both the rate of learning as well as overall performance in a
      sensorimotor task across subjects and develop a principled approach for the
      discovery of discriminative subgraphs of functional connectivity based on imaging
      acquired during practice. We discover two statistically significant subgraph
      regions: one involving multiple regions in the visual cortex and another
      involving the parietal operculum and planum temporale. High functional coherence
      in the former characterizes sessions in which subjects take longer to perform the
      task, while high coherence in the latter is associated with high learning rate
      (performance improvement across trials). Our proposed methodology is general, in
      that it can be applied to other cognitive tasks, to study learning or to
      differentiate between healthy patients and patients with neurological disorders,
      by revealing the salient interactions among brain regions associated with the
      observed global state. The discovery of such significant discriminative subgraphs
      promises a better data-driven understanding of the dynamic brain processes
      associated with high-level cognitive functions.

PMID- 29016688
TI  - TLR2/TLR4 activation induces Tregs and suppresses intestinal inflammation caused
      by Fusobacterium nucleatum in vivo.
AB  - Toll-like receptors (TLRs) 2 and 4 play critical roles in intestinal inflammation
      caused by Fusobacterium nucleatum (F. nucleatum) infection, but the role of
      TLR2/TLR4 in regulation of proinflammatory cytokines remains unknown. In this
      study, through microarray analysis and qRT-PCR, we showed that TLR2/TLR4 are
      involved in the F. nucleatum-induced inflammatory signaling pathway in Caco-2
      cells, C57BL/6 mice and human clinical specimens. In TLR2-/- and TLR4-/- mice, F.
      nucleatum infection resulted in increased colonization of the bacteria and
      production of the proinflammatory cytokines IL-8, IL-1beta and TNF-alpha. In
      addition, the ratio of Foxp3+ CD4+ T cells in the total CD4+ T cells in TLR2-/-
      and TLR4-/- mice was less than that in wild-type mice, and the ratio in hybrid
      mice was more than that in knockout mice, which suggested that TLR2/TLR4 mediated
      the number of Tregs. Furthermore, it was observed that inflammatory cytokine
      levels were reduced in TLR2-/- mice after Treg transfer. Thus, these data
      indicate that TLR2/TLR4 regulate F. nucleatum-induced inflammatory cytokines
      through Tregs in vivo.

PMID- 29016689
TI  - Modulation of the gut microbiota by the mixture of fish oil and krill oil in high
      fat diet-induced obesity mice.
AB  - Previous studies confirmed that dietary supplements of fish oil and krill oil can
      alleviate obesity in mice, but the underlying mechanism remains unclear. This
      study aims to discern whether oil treatment change the structure of the gut
      microbiota during the obesity alleviation. The ICR mice received high-fat diet
      (HFD) continuously for 12 weeks after two weeks of acclimatization with a
      standard chow diet, and the mice fed with a standard chow diet were used as the
      control. In the groups that received HFD with oil supplementation, the weight
      gains were attenuated and the liver index, total cholesterol, triglyceride and
      low-density lipoprotein cholesterol were reduced stepwise compared with the HFD
      group, and the overall structure of the gut microbiota, which was modulated in
      the HFD group, was shifted toward the structure found in the control group.
      Moreover, eighty-two altered operational taxonomic units responsive to oil
      treatment were identified and nineteen of them differing in one or more
      parameters associated with obesity. In conclusion, this study confirmed the
      effect of oil treatment on obesity alleviation, as well as on the microbiota
      structure alterations. We proposed that further researches are needed to
      elucidate the causal relationship between obesity alleviation and gut microbiota
      modulation.

PMID- 29016690
TI  - Expression profile of amh/Amh during bi-directional sex change in the protogynous
      orange-spotted grouper Epinephelus coioides.
AB  - Gonadal differentiation is tightly regulated by the initial sex determining gene
      and the downstream sex-related genes in vertebrates. However, sex change in fish
      can alter the sexual fate from one sex to the other. Chemical-induced maleness in
      the protogynous orange-spotted grouper is transient, and a reversible sex change
      occurs after the chemical treatment is withdrawn. We used these characteristics
      to study Amh signaling during bi-directional sex change in the grouper. We
      successfully induced the female-to-male sex change by chemical (aromatase
      inhibitor, AI, or methyltestosterone, MT) treatment. A dormant gonad (a low
      proliferation rate of early germ cells and no characteristics of both sexes) was
      found during the transient phase of reversible male-to-female sex change after
      the withdrawal of chemical administration. Our results showed that amh (anti
      mullerian hormone) and its receptor amhr2 (anti-mullerian hormone receptor type
      2) were significantly increased in the gonads during the process of female-to
      male sex change. Amh is expressed in the Sertoli cells surrounding the type A
      spermatogonia in the female-to-male grouper. Male-related gene (dmrt1 and sox9)
      expression was immediately decreased in MT-terminated males during the reversible
      male-to-female sex change. However, Amh expression was found in the surrounding
      cells of type A spermatogonia-like cells during the transient phase of reversible
      male-to-female sex change. This phenomenon is correlated with the dormancy of
      type A spermatogonia-like cells. Thus, Amh signaling is suggested to play roles
      in regulating male differentiation during the female-to-male sex change and in
      inhibiting type-A spermatogonia-like cell proliferation/differentiation during
      the reversible male-to-female sex change. We suggest that Amh signaling might
      play dual roles during bi-directional sex change in grouper.

PMID- 29016691
TI  - Generation of beta-lactoglobulin knock-out goats using CRISPR/Cas9.
AB  - Goat's milk, considered a substitute for cow's milk, has a high nutritional
      value. However, goat's milk contains various allergens, predominantly beta
      lactoglobulin (BLG). In this study, we employed the CRISPR/Cas9 system to target
      the BLG locus in goat fibroblasts for sgRNA optimization and generate BLG knock
      out goats through co-injection of Cas9 mRNA and small guide RNAs (sgRNAs) into
      goat embryos at the one-cell stage. We firstly tested sgRNA editing efficiencies
      in goat fibroblast cells, and approximately 8.00%-9.09% of the cells were
      modified in single sgRNA-guided targeting experiment. Among the kids, the genome
      targeting efficiencies of single sgRNA were 12.5% (10 ng/MUL sg1) and 0% (10
      ng/MUL sg2) and efficiencies of dual sgRNAs were 25.0% (25 ng/MUL sg2+sg3 group)
      and 28.6% (50 ng/MUL sg2+sg3 group). Relative expression of BLG in BLG knock-out
      goat mammary glands significantly (p < 0.01) decreased as well as other milk
      protein coding genes, such as CSN1S1, CSN1S2, CSN2, CSN3 and LALBA (p < 0.05). As
      expected, BLG protein had been abolished in the milk of the BLG knock-out goat.
      In addition, most of the targeted kids were chimeric (3/4), and their various
      body tissues were edited simultaneously. Our study thus provides a basis for
      optimizing the quality of goat milk, which can be applied to biomedical and
      agricultural research.

PMID- 29016693
TI  - Driving simulator scenarios and measures to faithfully evaluate risky driving
      behavior: A comparative study of different driver age groups.
AB  - To investigate the links between mental workload, age and risky driving, a cross
      sectional study was conducted on a driving simulator using several established
      and some novel measures of driving ability and scenarios of varying complexity. A
      sample of 115 drivers was divided into three age and experience groups: young
      inexperienced (18-21 years old), adult experienced (25-55 years old) and older
      adult (70-86 years old). Participants were tested on three different scenarios
      varying in mental workload from low to high. Additionally, to gain a better
      understanding of individuals' ability to capture and integrate relevant
      information in a highly complex visual environment, the participants' perceptual
      cognitive capacity was evaluated using 3-dimensional multiple object tracking (3D
      MOT). Results indicate moderate scenario complexity as the best suited to
      highlight well-documented differences in driving ability between age groups and
      to elicit naturalistic driving behavior. Furthermore, several of the novel
      driving measures were shown to provide useful, non-redundant information about
      driving behavior, complementing more established measures. Finally, 3D-MOT was
      demonstrated to be an effective predictor of elevated crash risk as well as
      decreased naturally-adopted mean driving speed, particularly among older adults.
      In sum, the present experiment demonstrates that in cases of either extreme high
      or low task demands, drivers can become overloaded or under aroused and thus task
      measures may lose sensitivity. Moreover, insights from the present study should
      inform methodological considerations for future driving simulator research.
      Importantly, future research should continue to investigate the predictive
      utility of perceptual-cognitive tests in the domain of driving risk assessment.

PMID- 29016692
TI  - Benefit of early discharge among patients with low-risk pulmonary embolism.
AB  - Clinical guidelines recommend early discharge of patients with low-risk pulmonary
      embolism (LRPE). This study measured the overall impact of early discharge of
      LRPE patients on clinical outcomes and costs in the Veterans Health
      Administration population. Adult patients with >=1 inpatient diagnosis for
      pulmonary embolism (PE) (index date) between 10/2011-06/2015, continuous
      enrollment for >=12 months pre- and 3 months post-index date were included. PE
      risk stratification was performed using the simplified Pulmonary Embolism
      Stratification Index. Propensity score matching (PSM) was used to compare 90-day
      adverse PE events (APEs) [recurrent venous thromboembolism, major bleed and
      death], hospital-acquired complications (HACs), healthcare utilization, and costs
      among short (<=2 days) versus long length of stay (LOS). Net clinical benefit was
      defined as 1 minus the combined rate of APE and HAC. Among 6,746 PE patients,
      95.4% were men, 22.0% were African American, and 1,918 had LRPE. Among LRPE
      patients, only 688 had a short LOS. After 1:1 PSM, there were no differences in
      APE, but short LOS had fewer HAC (1.5% vs 13.3%, 95% CI: 3.77-19.94) and
      bacterial pneumonias (5.9% vs 11.7%, 95% CI: 1.24-3.23), resulting in better net
      clinical benefit (86.9% vs 78.3%, 95% CI: 0.84-0.96). Among long LOS patients,
      HACs (52) exceeded APEs (14 recurrent DVT, 5 bleeds). Short LOS incurred lower
      inpatient ($2,164 vs $5,100, 95% CI: $646.8-$5225.0) and total costs ($9,056 vs
      $12,544, 95% CI: $636.6-$6337.7). LRPE patients with short LOS had better net
      clinical outcomes at lower costs than matched LRPE patients with long LOS.

PMID- 29016694
TI  - Efficacy of azole therapy for tegumentary leishmaniasis: A systematic review and
      meta-analysis.
AB  - BACKGROUND: Several controlled and uncontrolled studies addressing azole
      antifungal drugs for cutaneous and mucosal leishmaniasis have been published with
      inconclusive results. We conducted a systematic literature review of studies
      evaluating the efficacy and toxicity associated with azole therapy for
      tegumentary leishmaniasis. METHODOLOGY: PRISMA guidelines for systematic reviews
      and the Cochrane manual were followed, and the review methodology was registered
      (PROSPERO; CRD42016048668). Sources included the EMBASE, Web of Science, MEDLINE,
      LILACS, and IBECS databases along with a manual search of references from
      evaluated studies. Additional resources such as Google Scholar and
      clinicaltrials.gov were also searched. We included all studies reporting cure
      rate after cutaneous or mucosal leishmaniasis treatment with systemic azole
      drugs, regardless of their design. R software was used to estimate global rates
      of success and adverse events with each drug. The main outcome of interest was
      clinical cure, defined as complete re-epithelialization of all lesions. RESULTS:
      A total of 37 studies involving 1259 patients that reported outcomes after
      fluconazole (9), ketoconazole (14) and itraconazole (15) treatments were
      included. Only 14 (38%) were randomized controlled trials (RCT). The pooled azole
      final efficacy rate was 64% (CI95%: 57-70%) for all studies and 60% (CI95%: 50
      70%) (p = 0.41) if only RCTs studies were considered. Twenty-four studies were
      conducted in the Old World and 13 studies in the Americas. The final efficacy
      rate according to New and Old World were 62% (CI95%: 43-77%) and 66% (CI95%: 58
      73%), respectively. The final efficacy rate of azoles according to species were
      89% (CI95%: 50-98%) for L. mexicana; 88% for L. infantum (CI95%: 27-99%); 80% for
      L. donovani; 53% (CI95%: 29-76%) for L. major; 49% for L. braziliensis (CI95%: 21
      78%); and 15% (CI95%: 1-84%) for L. tropica. The cure rates were similar among
      the fluconazole, ketoconazole and itraconazole group arms (p = 0.89),
      specifically 61% (CI95%: 48-72%), 64% (CI95%: 44-80%) 65% (CI95%: 56-72%),
      respectively. Adverse events during fluconazole, itraconazole and ketoconazole
      therapy were reported in 7% (CI95%: 3-14%), 12% (CI95% 8-19%) and 13% (CI95%: 6
      29%) of treated patients, respectively, without difference among them (p = 0.35).
      This systematic review included studies with small samples and both non
      comparative and non-randomized studies and the main limitation was the low
      quality of the available studies. CONCLUSIONS: Available evidence suggests that
      fluconazole, ketoconazole and itraconazole have similar and modest efficacy rates
      for tegumentary leishmaniasis treatment. There is insufficient evidence to
      support the exclusive use of azole therapy as a single agent for leishmaniasis
      treatment.

PMID- 29016695
TI  - Oral anticoagulant persistence in patients with non-valvular atrial fibrillation:
      A cohort study using primary care data in Germany.
AB  - This study examined characteristics and treatment persistence among patients
      prescribed oral anticoagulants (OACs) for stroke prevention in non-valvular
      atrial fibrillation (NVAF). We identified 15,244 patients (51.8% male, 72.7% aged
      >=70) with NVAF and no prior OAC therapy who were prescribed apixaban (n =
      1,303), rivaroxaban (n = 5,742), dabigatran (n = 1,622) or vitamin-K antagonists
      (VKAs, n = 6,577) between 1-Dec-2012 and 31-Oct-2014 in German primary care
      (IMS(r) Disease Analyzer). We compared OAC persistence using Cox regression over
      patients' entire follow-up and using a data-driven time-partitioned approach
      (before/after 100 days) to handle non-proportional hazards. History of stroke
      risk factors (stroke/transient ischaemic attack [TIA] 15.2%; thromboembolism
      14.1%; hypertension 84.3%) and high bleeding risk (HAS-BLED score>=3 68.4%) was
      common. Apixaban-prescribed patients had more frequent history of stroke/TIA
      (19.7%) and high bleeding risk (72.6%) than other OACs. 12-month persistence
      rates were: VKA 57.5% (95% confidence interval (CI) 56.0-59.0%), rivaroxaban
      56.6% (54.9-58.2%), dabigatran 50.1% (47.2-53.1%), apixaban 62.9% (58.8-67.0%).
      Over entire follow-up, compared to VKA, non-persistence was similar with apixaban
      (adjusted hazard ratio 1.08, 95% CI 0.95-1.24) but higher with rivaroxaban (1.21,
      1.14-1.29) and dabigatran (1.53, 1.40-1.68). Using post-hoc time-partitioned
      approach: in first 100 days, non-persistence was higher with apixaban (1.37, 1.17
      1.59), rivaroxaban (1.41, 1.30-1.53) and dabigatran (1.91, 1.70-2.14) compared to
      VKA. Compared to apixaban, rivaroxaban non-persistence was similar (1.03, 0.89
      1.20), dabigatran was higher (1.39, 1.17-1.66). After 100 days, apixaban non
      persistence was lower than VKA (0.66, 0.52-0.85); rivaroxaban (0.97, 0.87-1.07)
      and dabigatran (1.10, 0.95-1.28) were similar to VKA. Furthermore, rivaroxaban
      (1.46, 1.13-1.88) and dabigatran (1.67, 1.26-2.19) non-persistence was higher
      than apixaban. This study describes real-world observations on OAC use,
      particularly early apixaban use following approval for NVAF, in Germany. We
      identified potential differential OAC prescribing and higher persistence with
      apixaban than other OACs after 100 days' treatment. Larger studies are needed
      with longer follow-up to establish long-term patterns.

PMID- 29016696
TI  - A battery-less and wireless wearable sensor system for identifying bed and chair
      exits in a pilot trial in hospitalized older people.
AB  - Falls in hospitals are common, therefore strategies to minimize the impact of
      these events in older patients and needs to be examined. In this pilot study, we
      investigate a movement monitoring sensor system for identifying bed and chair
      exits using a wireless wearable sensor worn by hospitalized older patients. We
      developed a movement monitoring sensor system that recognizes bed and chair
      exits. The system consists of a machine learning based activity classifier and a
      bed and chair exit recognition process based on an activity score function.
      Twenty-six patients, aged 71 to 93 years old, hospitalized in the Geriatric
      Evaluation and Management Unit participated in the supervised trials. They wore
      over their attire a battery-less, lightweight and wireless sensor and performed
      scripted activities such as getting off the bed and chair. We investigated the
      system performance in recognizing bed and chair exits in hospital rooms where
      RFID antennas and readers were in place. The system's acceptability was measured
      using two surveys with 0-10 likert scales. The first survey measured the change
      in user perception of the system before and after a trial; the second survey,
      conducted only at the end of each trial, measured user acceptance of the system
      based on a multifactor sensor acceptance model. The performance of the system
      indicated an overall recall of 81.4%, precision of 66.8% and F-score of 72.4% for
      joint bed and chair exit recognition. Patients demonstrated improved perception
      of the system after use with overall score change from 7.8 to 9.0 and high
      acceptance of the system with score >= 6.7 for all acceptance factors. The
      present pilot study suggests the use of wireless wearable sensors is feasible for
      detecting bed and chair exits in a hospital environment.

PMID- 29016697
TI  - Antinuclear antibodies and mortality in the National Health and Nutrition
      Examination Survey (1999-2004).
AB  - OBJECTIVE: Recent studies suggest antinuclear antibodies (ANA) may be related to
      mortality risk, but evidence is sparse and inconclusive. Thus, we investigated
      ANA associations with all-cause and cause-specific mortality in U.S. adults.
      METHODS: Our sample included 3357 adults (ages >=20 years) from the 1999-2004
      National Health and Nutrition Examination Survey with ANA measurements (1:80
      dilution) and mortality data through 2011 (median follow-up: 9.4 years). We
      estimated hazard ratios (HRs) and 95% confidence intervals (CIs) via weighted Cox
      regression to assess ANA associations with mortality from all causes,
      cardiovascular disease (CVD), and cancer. Models adjusted for age, sex,
      race/ethnicity, education, and obesity. Analyses examined mortality in the full
      sample and in subgroups based on self-reported histories of CVD and cancer, both
      overall and stratified by sex and age at enrollment. RESULTS: Overall, ANA were
      not strongly associated with death from all causes (HR: 1.13; CI: 0.79, 1.60),
      from CVD (HR: 1.60; CI: 0.80, 3.20), or from cancer (HR: 1.58; CI: 0.75, 3.33),
      though all three HR estimates exceeded 1. In the subgroup with a history of
      cancer, ANA were associated with elevated all-cause mortality in men (HR: 2.28;
      CI: 1.01, 5.14) and in participants who enrolled at age >=75 years (HR: 1.99; CI:
      1.04, 3.80). CONCLUSION: These findings suggest that ANA are not strongly
      associated with mortality in the general population. Longitudinal studies with
      repeated assessments are needed to understand the temporal relationship between
      ANA, aging-associated diseases, and mortality.

PMID- 29016700
TI  - A parallel approximate string matching under Levenshtein distance on graphics
      processing units using warp-shuffle operations.
AB  - Approximate string matching with k-differences has a number of practical
      applications, ranging from pattern recognition to computational biology. This
      paper proposes an efficient memory-access algorithm for parallel approximate
      string matching with k-differences on Graphics Processing Units (GPUs). In the
      proposed algorithm, all threads in the same GPUs warp share data using warp
      shuffle operation instead of accessing the shared memory. Moreover, we implement
      the proposed algorithm by exploiting the memory structure of GPUs to optimize its
      performance. Experiment results for real DNA packages revealed that the
      performance of the proposed algorithm and its implementation archived up to
      122.64 and 1.53 times compared to that of sequential algorithm on CPU and
      previous parallel approximate string matching algorithm on GPUs, respectively.

PMID- 29016698
TI  - Properties of halogenated and sulfonated porphyrins relevant for the selection of
      photosensitizers in anticancer and antimicrobial therapies.
AB  - The impact of substituents on the photochemical and biological properties of
      tetraphenylporphyrin-based photosensitizers for photodynamic therapy of cancer
      (PDT) as well as photodynamic inactivation of microorganisms (PDI) was examined.
      Spectroscopic and physicochemical properties were related with therapeutic
      efficacy in PDT of cancer and PDI of microbial cells in vitro. Less polar
      halogenated, sulfonamide porphyrins were most readily taken up by cells compared
      to hydrophilic and anionic porphyrins. The uptake and PDT of a hydrophilic
      porphyrin was significantly enhanced with incorporation in polymeric micelles
      (Pluronic L121). Photodynamic inactivation studies were performed against Gram
      positive (S. aureus, E. faecalis), Gram-negative bacteria (E. coli, P.
      aeruginosa, S. marcescens) and fungal yeast (C. albicans). We observed a 6 logs
      reduction of S. aureus after irradiation (10 J/cm2) in the presence of 20 MUM of
      hydrophilic porphyrin, but this was not improved with incorporation in Pluronic
      L121. A 2-3 logs reduction was obtained for E. coli using similar doses, and a
      decrease of 3-4 logs was achieved for C. albicans. Rational substitution of
      tetraphenylporphyrins improves their photodynamic properties and informs on
      strategies to obtain photosensitizers for efficient PDT and PDI. However, the
      design of the photosensitizers must be accompanied by the development of tailored
      drug formulations.

PMID- 29016699
TI  - MiR-137 inhibited cell proliferation and migration of vascular smooth muscle
      cells via targeting IGFBP-5 and modulating the mTOR/STAT3 signaling.
AB  - Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes to the
      development of cardiovascular diseases. Studies have shown the great impact of
      microRNAs (miRNAs) on the cell proliferation of VSMCs. This study examined the
      effects of miR-137 on the cell proliferation and migration of VSMCs and also
      explored the underlying molecular mechanisms. The mRNA and protein expression
      levels were determined by qRT-PCR and western blot assays, respectively. The CCK
      8 assay, wound healing assay and transwell migration assay were performed to
      measure cell proliferation and migration of VSMCs. The miR-137-targeted
      3'untranslated region of insulin-like growth factor-binding protein-5 (IGFBP-5)
      was confirmed by luciferase reporter assay. Platelet-derived growth factor-bb
      (PDGF-bb) treatment enhanced cell proliferation and suppressed the expression of
      miR-137 in VSMCs. The gain-of-function and loss-of-function assays showed that
      overexpression of miR-137 suppressed the cell proliferation and migration, and
      also inhibited the expression of matrix genes of VSMCs; down-regulation of miR
      137 had the opposite effects on VSMCs. Bioinformatics analysis and luciferase
      report assay results showed that IGFBP-5 was a direct target of miR-137, and miR
      137 overexpression suppressed the IGFBP-5 expression and down-regulation of miR
      137 increased the IGFBP-5 expression in VSMCs. PDGF-bb treatment also increased
      the IGFBP-5 mRNA expression. In addition, enforced expression of IGFBP-5 reversed
      the inhibitory effects of miR-137 on cell proliferation and migration of VSMCs.
      More importantly, overexpression of miR-137 also suppressed the activity of
      mTOR/STAT3 signaling in VSMCs. Taken together, the results suggest that miR-137
      may suppress cell proliferation and migration of VSMCs via targeting IGFBP-5 and
      modulating mTOR/STAT3 signaling pathway.

PMID- 29016702
TI  - A Commentary on the Limits of Alcoholic Beverage Policies.
AB  - Providing one set of policy measures for all countries as if they were a single,
      homogeneous entity does not appear to be evidence-based, according to recent
      research on the effectiveness of alcoholic beverage control policies. Contextual
      and cultural determinants-social, economic, demographic, cultural and political
      appear to be major factors of influencing change in drinking trends, drinking
      patterns and drinking-related harms. The variable interplay between contextual
      determinants and alcohol control policy measures implies diverse impacts on
      consumption and harm according to time, and to the different countries and groups
      of countries. In addition, epidemiology research manifests some limitations when
      applied to alcohol drinking and results are transferred from one culture to
      another. The conditions of individual cultures and countries should be considered
      when planning and evaluating alcohol control policies.

PMID- 29016701
TI  - Modifying Alcohol Consumption to Reduce Obesity: A Randomized Controlled
      Feasibility Study of a Complex Community-based Intervention for Men.
AB  - Objectives: Being obese and drinking more than 14 units of alcohol per week
      places men at very high risk of developing liver disease. This study assessed the
      feasibility of a trial to reduce alcohol consumption. It tested the recruitment
      strategy, engagement with the intervention, retention and study acceptability.
      Methods: Men aged 35-64 years who drank >21 units of alcohol per week and had a
      BMI > 30 were recruited by two methods: from GP patient registers and by
      community outreach. The intervention was delivered by a face to face session
      followed by a series of text messages. Trained lay people (Study Coordinators)
      delivered the face to face session. Participants were followed up for 5 months
      from baseline to measure weekly alcohol consumption and BMI. Results: The
      recruitment target of 60 was exceeded, with 69 men recruited and randomized. At
      baseline, almost all the participants (95%) exceeded the threshold for a 19-fold
      increase in the risk of dying from liver disease. The intervention was delivered
      with high fidelity. A very high follow-up rate was achieved (98%) and the
      outcomes for the full trial were measured. Process evaluation showed that
      participants responded as intended to key steps in the behaviour change strategy.
      The acceptability of the study methods was high: e.g. 80% of men would recommend
      the study to others. Conclusions: This feasibility study identified a group at
      high risk of liver disease. It showed that a full trial could be conducted to
      test the effectiveness and cost-effectiveness of the intervention. Trial
      registration: Current controlled trials: ISRCTN55309164. Trial funding: National
      Institute for Health Research Health Technology Assessment (NIHR HTA). Short
      summary: This feasibility study recruited 69 men at high risk of developing liver
      disease. The novel intervention, to reduce alcohol consumption through the
      motivation of weight loss, was well received. A very high follow-up rate was
      achieved. Process evaluation showed that participants engaged with key components
      of the behaviour change strategy.

PMID- 29016703
TI  - beta-arrestin 2 mediates cardiac ischemia-reperfusion injury via inhibiting GPCR
      independent cell survival signalling.
AB  - Aims: Ischemic heart disease is a leading cause of morbidity and mortality
      worldwide. Although timely restoration of coronary blood flow (reperfusion) is
      the most effective therapeutics of myocardial infarction, reperfusion causes
      further cardiac damage, i.e. ischemia-reperfusion (I/R) injury. beta-arrestins
      (Arrbs) have been traditionally defined as negative regulators of G protein
      coupled receptor (GPCR) signalling, but recent studies have shown that they are
      essential for G protein-independent, GPCR-mediated biased signalling. Several
      ligands have been reported to be cardioprotective via Arrbs dependent pathway.
      However, it is unclear whether Arrbs exert receptor-independent physiological or
      pathological functions in the heart. Here, we sought to determine whether and how
      Arrbs play a role in regulating cardiomyocyte viability and myocardial
      remodelling following I/R injury. Methods and results: The expression of beta
      arrestin 2 (Arrb2), but not beta-arrestin 1 (Arrb1), is upregulated in rat hearts
      subjected to I/R injury, or in cultured neonatal rat cardiomyocytes treated with
      hypoxia-reoxygenation (H/R) injury. Deficiency of Arrb2 in cultured neonatal rat
      cardiomyocytes alleviates H/R-induced cardiomyocyte death and Arrb2-/- mice are
      resistant to myocardial damage caused by I/R injury. In contrast, upregulation of
      Arrb2 triggers cardiomyocyte death and exaggerates I/R (or H/R)-induced
      detrimental effects. Mechanically, Arrb2 induces cardiomyocyte death by
      interacting with the p85 subunit of PI3K, and negatively regulating the formation
      of p85-PI3K/CaV3 survival complex, thus blocking activation of PI3K-Akt-GSK3beta
      cell survival signalling pathway. Conclusion: We define an upregulation of Arrb2
      as a pathogenic factor in cardiac I/R injury, and also reveal a novel GPCR
      independent mechanism of Arrb2-mediated cell death signalling in the heart.

PMID- 29016705
TI  - Is carbohydrate deficient transferrin (CDT) a useful biomarker to identify
      alcohol abuse in advanced liver fibrosis?

PMID- 29016704
TI  - Investigation of cardiac fibroblasts using myocardial slices.
AB  - Aims: Cardiac fibroblasts (CFs) are considered the principal regulators of
      cardiac fibrosis. Factors that influence CF activity are difficult to determine.
      When isolated and cultured in vitro, CFs undergo rapid phenotypic changes
      including increased expression of alpha-SMA. Here we describe a new model to
      study CFs and their response to pharmacological and mechanical stimuli using in
      vitro cultured mouse, dog and human myocardial slices. Methods and results:
      Unloading of myocardial slices induced CF proliferation without alpha-SMA
      expression up to 7 days in culture. CFs migrating onto the culture plastic
      support or cultured on glass expressed alphaSMA within 3 days. The cells on the
      slice remained alphaSMA(-) despite transforming growth factor-beta (20 ng/ml) or
      angiotensin II (200 uM) stimulation. When diastolic load was applied to
      myocardial slices using A-shaped stretchers, CF proliferation was significantly
      prevented at Days 3 and 7 (P < 0.001). Conclusions: Myocardial slices allow the
      study of CFs in a multicellular environment and may be used to effectively study
      mechanisms of cardiac fibrosis and potential targets.

PMID- 29016707
TI  - Minimal Clinical Impact of Intraoperative Examination of Sentinel Lymph Nodes in
      Patients With Ductal Carcinoma In Situ: An Opportunity for Improved Resource
      Utilization.
AB  - Objectives: There is little information regarding sentinel lymph node (SLN)
      frozen-section examination in patients with a history of ductal carcinoma in situ
      (DCIS). We evaluated the usage, clinical impact, and pathology resources used for
      SLN cryosectioning in mastectomy cases with a DCIS history. Methods: Mastectomies
      with SLNs submitted from 2012 to 2013 at a tertiary care center were analyzed.
      Medicare reimbursement was used to estimate pathology health care expenditures of
      intraoperative frozen sections. Results: There was no difference in the rate of
      SLN frozen-section examination or parts submitted, total blocks frozen, total
      blocks submitted, or total SLNs identified per case between the DCIS (n = 139)
      and invasive (n = 369) groups. Nine patients with DCIS had SLN metastases (three
      macrometastases, two micrometastases, and four isolated tumor cells), all of
      which were examined by frozen section. Only the macrometastases were identified
      by cryosectioning, which led to two synchronous axillary lymph node dissections
      that did not yield any additional positive nodes. A total of $19,313 was spent
      for pathology per DCIS patient with surgical management affected, whereas only
      $1,019 was spent per invasive carcinoma patient affected. Conclusions: Decreasing
      SLN frozen-section use in patients with a history of DCIS represents an
      opportunity for pathology cost containment.

PMID- 29016708
TI  - Testing the Efficacy of Alcohol Labels with Standard Drink Information and
      National Drinking Guidelines on Consumers' Ability to Estimate Alcohol
      Consumption.
AB  - Aims: Despite the introduction of national drinking guidelines in Canada, there
      is limited public knowledge of them and low understanding of 'standard drinks
      (SDs)' which limits the likelihood of guidelines affecting drinking behaviour.
      This study tests the efficacy of alcohol labels with SD information and Canada's
      Low-Risk Drinking Guidelines (LRDGs) as compared to %ABV labels on consumers'
      ability to estimate alcohol intake. It also examines the label size and format
      that best supports adults' ability to make informed drinking choices. Methods:
      This research consisted of a between-groups experiment (n = 2016) in which
      participants each viewed one of six labels. Using an online survey, participants
      viewed an alcohol label and were asked to estimate: (a) the amount in a SD; (b)
      the number of SDs in an alcohol container and (c) the number of SDs to consume to
      reach the recommended daily limit in Canada's LRDG. Results: Results indicated
      that labels with SD and LRDG information facilitated more accurate estimates of
      alcohol consumption and awareness of safer drinking limits across different
      beverage types (12.6% to 58.9% increase in accuracy), and labels were strongly
      supported among the majority (66.2%) of participants. Conclusion: Labels with SD
      and LRDG information constitute a more efficacious means of supporting accurate
      estimates of alcohol consumption than %ABV labels, and provide evidence to inform
      potential changes to alcohol labelling regulations. Further research testing
      labels in real-world settings is needed. Short summary: Results indicate that the
      introduction of enhanced alcohol labels combining standard drink information and
      national drinking guidelines may be an effective way to improve drinkers' ability
      to accurately assess alcohol consumption and monitor intake relative to
      guidelines. Overall support for enhanced labels suggests probable acceptability
      of introduction at a population level.

PMID- 29016706
TI  - MicroRNA-532 protects the heart in acute myocardial infarction, and represses
      prss23, a positive regulator of endothelial-to-mesenchymal transition.
AB  - Aims: Acute myocardial infarction (MI) leads to cardiac remodelling and
      development of heart failure. Insufficient myocardial capillary density after MI
      is considered a critical determinant of this process. MicroRNAs (miRs), negative
      regulators of gene expression, have emerged as important players in MI. We
      previously showed that miR-532-5p (miR-532) is up-regulated by the beta-arrestin
      biased beta-adrenergic receptor antagonist (beta-blocker) carvedilol, which
      activates protective pathways in the heart independent of G protein-mediated
      second messenger signalling. Here, we hypothesize that beta2-adrenergic
      receptor/beta-arrestin-responsive miR-532 confers cardioprotection against MI.
      Methods and results: Using cultured cardiac endothelial cell (CEC) and in vivo
      approaches, we show that CECs lacking miR-532 exhibit increased transition to a
      fibroblast-like phenotype via endothelial-to-mesenchymal transition (EndMT),
      while CECs over-expressing miR-532 display decreased EndMT. We also demonstrate
      that knockdown of miR-532 in mice causes abnormalities in cardiac structure and
      function as well as reduces CEC proliferation and cardiac vascularization after
      MI. Mechanistically, cardioprotection elicited by miR-532 is in part attributed
      to direct repression of a positive regulator of maladaptive EndMT, prss23 (a
      protease serine 23) in CECs. Conclusions: In conclusion, these findings reveal a
      pivotal role for miR-532-prss23 axis in regulating CEC function after MI, and
      this novel axis could be suitable for therapeutic intervention in ischemic heart
      disease.

PMID- 29016709
TI  - The Role of General Practitioners in the 2015 French Guidelines on Alcohol
      Misuse.

PMID- 29016711
TI  - Personalized Digital Interventions Showed no Impact on Risky Drinking in Young
      Adults: A Pilot Randomized Controlled Trial.
AB  - Aim: To assess the effectiveness of two personalized digital interventions
      (OneTooMany and Drinks Meter) compared to controls. Method: Randomized controlled
      trial (AEARCTR-0,001,082). Volunteers for the study, aged 18-30, were randomly
      allocated to one of two interventions or one of two control groups and were
      followed up 4 weeks later. Primary outcomes were AUDIT-C, drinking harms and pre
      loading. Drinks Meter provided participants with brief screening and advice for
      alcohol in addition to normative feedback, information on calories consumed and
      money spent. OneTooMany presented a series of socially embarrassing scenarios
      that may occur when drinking, and participants were scored according to if/how
      recently they had been experienced. Results: The study failed to recruit and
      obtain sufficient follow-up data to reach a prior estimated power for detecting a
      difference between groups and there was no indication in the analysable sample of
      402 subjects of a difference on the primary outcome measures (Drinks Meter; AUDIT
      C IRR = 0.98 (0.89-1.09); Pre-loading IRR = 1.01 (0.95-1.07); Harms IRR = 0.97
      (0.79-1.20); OneTooMany; AUDIT-C IRR = 0.96 (0.86-1.07); Pre-loading IRR = 0.99
      (0.93-1.06); Harms IRR = 1.16 (0.94-1.43). Conclusion: Further research is needed
      on the efficacy of such instruments and their ingredients. However, recruitment
      and follow-up are a challenge.

PMID- 29016710
TI  - Preliminary Evidence for Disrupted Nucleus Accumbens Reactivity and Connectivity
      to Reward in Binge Drinkers.
AB  - Aims: Dysfunctional brain reward circuitry, particularly in the nucleus accumbens
      (NAcc), has been proposed as a risk factor for alcohol use disorder (AUD). This
      risk factor may be evident in binge drinkers (BD), who are at high risk for
      developing AUD. We examined whole-brain and NAcc reactivity to reward in BD
      compared to non-binge drinkers (NBD), hypothesizing that groups would differ in
      their neural reactivity and connectivity. Methods: Healthy BD (N = 27) and NBD (N
      = 23)-none meeting AUD criteria-completed a reward-guessing game, the 'Doors'
      task, during functional magnetic resonance imaging. We conducted an exploratory
      whole-brain search for group differences, but given our a priori hypotheses, we
      also extracted activation from the NAcc to examine reactivity during reward (Win
      > Loss) and functional connectivity (FC) to the prefrontal cortex. Results:
      Compared to NBD, BD exhibited greater activation in both the right and left NAcc
      during reward relative to loss. Additionally, NBD drinkers exhibited positive FC
      between the NAcc and dorsal anterior cingulate (dACC) whereas the BD showed
      negative FC between these regions. Furthermore, less NAcc-dACC FC was related to
      more past month alcohol use. Conclusions: Our results provide preliminary
      evidence that BD exhibit greater NAcc activation during reward receipt relative
      to loss. This is consistent with the broader AUD literature and suggests aberrant
      neural reactivity may precede disorder onset. In addition, BD exhibited less NAcc
      dACC FC, perhaps reflecting deficient regulation of activation to rewards
      compared to losses. This profile of reward brain circuitry could represent neural
      correlates of vulnerability for AUD. Short summary: Healthy binge drinkers, at
      risk for alcohol use disorder, exhibited greater nucleus accumbens activation
      during reward relative to loss. In addition, binge drinkers exhibited reduced
      connectivity between the nucleus accumbens and dorsal anterior cingulate, which
      was associated with more past month alcohol use.

PMID- 29016712
TI  - Forty Years of State Alcohol and Pregnancy Policies in the USA: Best Practices
      for Public Health or Efforts to Restrict Women's Reproductive Rights?
AB  - Aims: Alcohol consumption during pregnancy remains a public health problem
      despite >40 years of attention. Little is known about how state policies have
      evolved and whether policies represent public health goals or efforts to restrict
      women's reproductive rights. Methods: Our data set includes US state policies
      from 1970 through 2013 obtained through original legal research and from the
      National Institute for Alcohol Abuse and Alcoholism's (NIAAA)'s Alcohol Policy
      Information System. Policies were classified as punitive to women or supportive
      of them. The association between numbers of punitive policies and supportive
      policies in 2013 with a measure of state restrictions on reproductive rights and
      Alcohol Policy Effectiveness Scores (APS) was estimated using a Pearson's
      correlation. Results: The number of states with alcohol and pregnancy policies
      has increased from 1 in 1974 to 43 in 2013. Through the 1980s, state policy
      environments were either punitive or supportive. In the 1990s, mixed punitive and
      supportive policy environments began to be the norm, with punitive policies added
      to supportive ones. No association was found between the number of supportive
      policies in 2013 and a measure of reproductive rights policies or the APS, nor
      was there an association between the number of punitive policies and the APS. The
      number of punitive policies was positively associated, however, with restrictions
      on reproductive rights. Conclusion: Punitive alcohol and pregnancy policies are
      associated with efforts to restrict women's reproductive rights rather than
      effective efforts to curb public health harms due to alcohol use in the general
      population. Future research should explore the effects of alcohol and pregnancy
      policies. Short Summary: The number of states with alcohol and pregnancy policies
      has increased since 1970 (1 in 1974 and 43 in 2013). Alcohol and pregnancy
      policies are becoming increasingly punitive. These punitive policies are
      associated with efforts to restrict women's reproductive rights rather than
      policies that effectively curb alcohol-related public health harms.

PMID- 29016713
TI  - Heavy Drinkers and the Potential Impact of Minimum Unit Pricing-No Single or
      Simple Effect?
AB  - Aims: To explore the potential impact of a minimum unit price (MUP: 50 pence per
      UK unit) on the alcohol consumption of ill Scottish heavy drinkers. Methods:
      Participants were 639 patients attending alcohol treatment services or admitted
      to hospital with an alcohol-related condition. From their reported expenditure on
      alcohol in their index week, and assuming this remained unchanged, we estimated
      the impact of a MUP (50 ppu) on future consumption. (Around 15% purchased from
      both the more expensive on-sale outlets (hotels, pubs, bars) and from off-sales
      (shops and supermarkets). For them we estimated the change in consumption that
      might follow MUP if (i) they continued this proportion of 'on-sales' purchasing
      or (ii) their reported expenditure was moved entirely to off-sale purchasing (to
      maintain consumption levels)). Results: Around 69% of drinkers purchased
      exclusively off-sale alcohol at <50 ppu. Their drinking, post MUP, may reduce by
      a mean of 33%. For this group, from a population of very heavy, ill consumers, we
      were unable to show a differential effect across multiple deprivation quintiles.
      For other drinkers there might be no reduction, especially if after MUP there
      were many products priced close to 50 ppu. Moving away from on-sales purchases
      could support, for some, an increase in consumption. Conclusions: While a
      proportion of our harmed, heavy drinkers might be able to mitigate the impact of
      MUP by changing purchasing habits, the majority are predicted to reduce
      purchasing. This analysis, focusing specifically on harmed drinkers, adds a
      unique dimension to the evidence base informing current pricing policy. Short
      Summary: From drink purchasing data of heavy drinkers, we estimated the impact of
      legislating L0.50 minimum unit price. Over two thirds of drinkers, representing
      all multiple deprivation quintiles, were predicted to decrease alcohol
      purchasing; remainder, hypothetically, could maintain consumption. Our data
      address an important gap within the evidence base informing policy.

PMID- 29016714
TI  - Low-energy defibrillation with nanosecond electric shocks.
AB  - Aims: Reliable defibrillation with reduced energy deposition has long been the
      focus of defibrillation research. We studied the efficacy of single shocks of 300
      ns duration in defibrillating rabbit hearts as well as the tissue damage they may
      cause. Methods and results: New Zealand white rabbit hearts were Langendorff
      perfused and two planar electrodes were placed on either side of the heart.
      Shocks of 300 ns duration and 0.3-3 kV amplitude were generated with a
      transmission line generator. Single nanosecond shocks consistently induced waves
      of electrical activation, with a stimulation threshold of 0.9 kV (over 3 cm) and
      consistent activation for shock amplitudes of 1.2 kV or higher (9/9 successful
      attempts). We induced fibrillation (35 episodes in 12 hearts) and found that
      single shock nanosecond-defibrillation could consistently be achieved, with a
      defibrillation threshold of 2.3-2.4 kV (over 3 cm), and consistent success at 3
      kV (11/11 successful attempts). Shocks uniformly depolarized the tissue, and the
      threshold energy needed for nanosecond defibrillation was almost an order of
      magnitude lower than the energy needed for defibrillation with a monophasic 10 ms
      shock delivered with the same electrode configuration. For the parameters studied
      here, nanosecond defibrillation caused no baseline shift of the transmembrane
      potential (that could be indicative of electroporative damage), no changes in
      action potential duration, and only a brief change of diastolic interval, for one
      beat after the shock was delivered. Histological staining with tetrazolium
      chloride and propidium iodide showed that effective defibrillation was not
      associated with tissue death or with detectable electroporation anywhere in the
      heart (six hearts). Conclusion: Nanosecond-defibrillation is a promising
      technology that may allow clinical defibrillation with profoundly reduced
      energies.

PMID- 29016717
TI  - Reply: The role of general practitioners in the 2015 French guidelines on alcohol
      misuse.

PMID- 29016716
TI  - "We Have a Right to Know": Exploring Consumer Opinions on Content, Design and
      Acceptability of Enhanced Alcohol Labels.
AB  - Aims: This study aimed to refine content and design of an enhanced alcohol label
      to provide information that best supports informed drinking and to gauge consumer
      acceptability of enhanced alcohol labels among a subset of consumers. Methods:
      Five focus groups (n = 45) were conducted with stakeholders and the general
      public (age 19+) across one jurisdiction in northern Canada. Interviews were
      transcribed and analyzed using NVivo software. Results: The majority of
      participants showed strong support for enhanced alcohol labels with an emphasis
      on the consumers' right to know about the health risks related to alcohol.
      Participants preferred larger labels that included standard drink (SD)
      information, national low-risk drinking guidelines presented as a chart with
      pictograms, cancer health messaging and a pregnancy warning. Supporting
      introduction of the labels with a web resource and an educational campaign was
      also recommended. Conclusions: Displaying enhanced labels on alcohol containers
      that include SD information, low-risk drinking guidelines and other health
      messaging in an accessible format may be an effective way to better inform
      drinkers about their consumption and increase awareness of alcohol-related health
      risks. Introduction of enhanced labels shows potential for consumer support.
      Short summary: Focus group findings indicate strong support for enhanced alcohol
      labels displaying SD information, national drinking guidelines, health messaging
      and a pregnancy warning. Introduction of enhanced alcohol labels in tandem with
      an educational campaign may be an effective way to better inform Canadian
      drinkers and shows potential for consumer support.

PMID- 29016718
TI  - Population Alcohol Consumption as a Predictor of Alcohol-Specific Deaths: A Time
      Series Analysis of Aggregate Data.
AB  - Aims: The study examines whether the number of alcohol-specific deaths can be
      predicted by population total and/or beverage-specific alcohol consumption and
      if, how precisely. The data are annual series of spirits, wine, beer and total
      consumption and alcohol-specific deaths in Finland in the years 1969-2015.
      Methods: We specify a Auto Regressive Distributed Lags model with cointegrated
      variables, to be used in prediction. In our model, the number of alcohol-specific
      deaths is the response variable, and log of spirits consumption and log of non
      spirits consumption, are the explanatory variables. The response variable has one
      added annual lag and the explanatory variables have both four annual added lags
      in the model. Results: In our data alcohol-specific deaths, log of spirits and
      log of non-spirits consumption are significantly cointegrated. The precision of
      the estimated model is good. The prediction results include prediction of the
      2008 downturn in alcohol deaths, using the data from the years 1969-2004,
      forecasting the as yet unknown 2016 alcohol deaths on the basis of known values
      of alcohol consumption up to 2016, and forecasts of future (2017-2020) alcohol
      deaths from 2016 on. Forecasted effects of a proposed Finnish alcohol policy
      change, leading to six percent total consumption increase, are estimated.
      Conclusions: The number of alcohol-specific deaths can be predicted with an
      appropriate time-series regression model on the basis of population consumption.
      It is important to consider also beverage type because of the improved predictive
      power. The model is useful in an evaluation of proposed alcohol policy changes.

PMID- 29016715
TI  - Matrix metalloproteinase-2 knockout prevents angiotensin II-induced vascular
      injury.
AB  - Aims: Matrix metalloproteinases (MMPs) have been implicated in the development of
      hypertension in animal models and humans. Mmp2 deletion did not change Ang II
      induced blood pressure (BP) rise. However, whether Mmp2 knockout affects
      angiotensin (Ang) II-induced vascular injury has not been tested. We sought to
      determine whether Mmp2 knockout will prevent Ang II-induced vascular injury.
      Methods and results: A fourteen-day Ang II infusion (1000 ng/kg/min, SC)
      increased systolic BP, decreased vasodilatory responses to acetylcholine, induced
      mesenteric artery (MA) hypertrophic remodelling, and enhanced MA stiffness in
      wild-type (WT) mice. Ang II enhanced aortic media and perivascular reactive
      oxygen species generation, aortic vascular cell adhesion molecule-1 and monocyte
      chemotactic protein-1 expression, perivascular monocyte/macrophage and T cell
      infiltration, and the fraction of spleen activated CD4+CD69+ and CD8+CD69+ T
      cells, and Ly-6Chi monocytes. Study of intracellular signalling showed that Ang
      II increased phosphorylation of epidermal growth factor receptor and
      extracellular-signal-regulated kinase 1/2 in vascular smooth muscle cells
      isolated from WT mice. All these effects were reduced or prevented by Mmp2
      knockout, except for systolic BP elevation. Ang II increased Mmp2 expression in
      immune cells infiltrating the aorta and perivascular fat. Bone marrow (BM)
      transplantation experiments revealed that in absence of MMP2 in immune cells, Ang
      II-induced BP elevation was decreased, and that when MMP2 was deficient in either
      immune or vascular cells, Ang II-induced endothelial dysfunction was blunted.
      Conclusions: Mmp2 knockout impaired Ang II-induced vascular injury but not BP
      elevation. BM transplantation revealed a role for immune cells in Ang II-induced
      BP elevation, and for both vascular and immune cell MMP2 in Ang II-induced
      endothelial dysfunction.

PMID- 29016719
TI  - You Wouldn't Sober, You Shouldn't Drunk: A Behavioural Change Approach to
      Changing Attitudes and Responses to Unwanted Sexual Attention in Pubs and Clubs.
AB  - Aims: The objective was to evaluate a campaign designed to influence social norms
      and re-establish boundaries around the issue of unwanted sexual attention in pubs
      and clubs. In particular, the campaign aimed to raise awareness, and reduce the
      acceptability, of unwanted sexual attention when drunk. Methods: A before-after
      with-control group study design was used to evaluate campaign effectiveness. The
      data was further segmented to explore gender differences and between individuals
      who reported enjoying going out to get drunk and those who did not. Results: The
      experimental group with campaign recall demonstrated a significant change in
      their attitudes to harmful drinking behaviours and unwanted sexual attention
      compared to the control group. A number of gender differences as well as drink
      enjoyment-related differences pre- and post-campaign were observed. Female
      respondents who were able to recall the campaign demonstrated a significantly
      lower tolerance of unwanted sexual attention than those who were unable to recall
      it in either the experimental or control regions. The campaign had limited impact
      on people who enjoy drunken night outs (DNOs). However, those who do not enjoy
      DNOs demonstrated significantly higher negative attitudes towards harmful
      drinking post-campaign recall. Conclusion: The campaign was effective in shifting
      attitudes towards unwanted sexual attention and harmful drinking behaviour. This
      was particularly observed among female respondents and those who do not enjoy
      DNOs. Short summary: Drinkaware's 'You Wouldn't Sober, You Shouldn't Drunk'
      behavioural change campaign targets young adults living in North-West England
      participating in 'drunken nights out'. The experimental group with campaign
      recall demonstrated a significant change in their attitudes to harmful drinking
      behaviours and unwanted sexual attention compared to the control group.

PMID- 29016720
TI  - Predicting Regulatory Compliance in Beer Advertising on Facebook.
AB  - Aims: The prevalence of alcohol advertising has been growing on social media
      platforms. The purpose of this study was to evaluate alcohol advertising on
      Facebook for regulatory compliance and thematic content. Methods: A total of 50
      Budweiser and Bud Light ads posted on Facebook within 1 month of the 2015 NFL
      Super Bowl were evaluated for compliance with a self-regulated alcohol
      advertising code and for thematic content. An exploratory sensitivity/specificity
      analysis was conducted to determine if thematic content could predict code
      violations. Results: The code violation rate was 82%, with violations prevalent
      in guidelines prohibiting the association of alcohol with success (Guideline 5)
      and health benefits (Guideline 3). Overall, 21 thematic content areas were
      identified. Displaying the product (62%) and adventure/sensation seeking (52%)
      were the most prevalent. There was perfect specificity (100%) for 10 content
      areas for detecting any code violation (animals, negative emotions, positive
      emotions, games/contests/promotions, female characters, minorities, party,
      sexuality, night-time, sunrise) and high specificity (>80%) for 10 content areas
      for detecting violations of guidelines intended to protect minors (animals,
      negative emotions, famous people, friendship, games/contests/promotions,
      minorities, responsibility messages, sexuality, sunrise, video games).
      Conclusions: The high prevalence of code violations indicates a failure of self
      regulation to prevent potentially harmful content from appearing in alcohol
      advertising, including explicit code violations (e.g. sexuality). Routine
      violations indicate an unwillingness to restrict advertising content for public
      health purposes, and statutory restrictions may be necessary to sufficiently
      deter alcohol producers from repeatedly violating marketing codes. Short summary:
      Violations of a self-regulated alcohol advertising code are prevalent in a sample
      of beer ads published on Facebook near the US National Football League's Super
      Bowl. Overall, 16 thematic content areas demonstrated high specificity for code
      violations. Alcohol advertising codes should be updated to expressly prohibit the
      use of such content.

PMID- 29016721
TI  - No Impact of Calorie or Unit Information on Ad Libitum Alcohol Consumption.
AB  - Aims: To investigate the impact of unit and calorie information on drinking
      behaviour in an ad libitum taste test paradigm. Methods: In this experimental
      human laboratory study, participants were randomized to one of four conditions,
      balanced by gender, using a 2 (unit information: present vs. absent) * 2 (calorie
      information: present vs. absent) between-subjects design. The percentage of beer
      consumed during the taste test was the primary outcome measure. Results: Among
      this largely undergraduate student population, we found no evidence that either
      unit or calorie information impacted alcohol consumption in an ad libitum taste
      test. A manipulation check indicated that few of the participants receiving
      either unit and/or calorie information could accurately recall the number of
      units and/or calories in the beverages provided to them, indicating low levels of
      engagement with this information. Analysis of qualitative reactions to calorie
      and unit labelling indicated possible negative unintended consequences of calorie
      and unit information, including using unit information to facilitate consumption
      of higher strength beverages, and calorie information to reduce food consumption
      prior to a drinking episode. Conclusion: We find no evidence to support an effect
      of unit or calorie information, a public-health initiative supported by the
      alcohol industry, on drinking behaviour. It is possible that compulsory unit and
      calorie labelling, at least in the numeric format used here, would have no effect
      on alcohol intake and may even have some negative unintended consequences among
      certain populations.

PMID- 29016723
TI  - Use of the Mean Abnormal Result Rate (MARR) to Gauge Changes in Family
      Physicians' Selectivity of Laboratory Test Ordering, 2010-2015.
AB  - Objectives: The mean abnormal result rate (MARR) has recently been advanced as a
      metric of laboratory test appropriateness. We used the MARR metric to examine
      patterns of change in family physician test requisitions over time. Methods: We
      accessed the Laboratory Information System of Calgary Laboratory Services for
      family physician-ordered testing on outpatients to gather aggregate test and
      abnormal result counts from 2010 to 2015. Results: Over the 6 years, there was an
      annual average of 3,401,553 tests for 411,295 distinct patients on their first
      test requisition for the year. The MARR increased from 8.1% to 9.0% through this
      period. Conclusions: The MARR for Calgary and surrounding area gives tentative
      evidence of a gradual increase in physician test selectivity in recent years.
      Further data from other catchment areas are needed before making assertions about
      broader trends in physician awareness of laboratory resource use.

PMID- 29016722
TI  - Hierarchical statistical techniques are necessary to draw reliable conclusions
      from analysis of isolated cardiomyocyte studies.
AB  - Aims: It is generally accepted that post-MI heart failure (HF) changes a variety
      of aspects of sarcoplasmic reticular Ca2+ fluxes but for some aspects there is
      disagreement over whether there is an increase or decrease. The commonest
      statistical approach is to treat data collected from each cell as independent,
      even though they are really clustered with multiple likely similar cells from
      each heart. In this study, we test whether this statistical assumption of
      independence can lead the investigator to draw conclusions that would be
      considered erroneous if the analysis handled clustering with specific statistical
      techniques (hierarchical tests). Methods and results: Ca2+ transients were
      recorded in cells loaded with Fura-2AM and sparks were recorded in cells loaded
      with Fluo-4AM. Data were analysed twice, once with the common statistical
      approach (assumption of independence) and once with hierarchical statistical
      methodologies designed to allow for any clustering. The statistical tests found
      that there was significant hierarchical clustering. This caused the common
      statistical approach to underestimate the standard error and report artificially
      small P values. For example, this would have led to the erroneous conclusion that
      time to 50% peak transient amplitude was significantly prolonged in HF. Spark
      analysis showed clustering, both within each cell and also within each rat, for
      morphological variables. This means that a three-level hierarchical model is
      sometimes required for such measures. Standard statistical methodologies, if used
      instead, erroneously suggest that spark amplitude is significantly greater in HF
      and spark duration is reduced in HF. Conclusion: Ca2+ fluxes in isolated
      cardiomyocytes show so much clustering that the common statistical approach that
      assumes independence of each data point will frequently give the false appearance
      of statistically significant changes. Hierarchical statistical methodologies need
      a little more effort, but are necessary for reliable conclusions. We present cost
      free simple tools for performing these analyses.

PMID- 29016725
TI  - Is Drinking Contagious? An Analysis of the Collectivity of Drinking Behavior
      Theory Within a Multilevel Framework.
AB  - Aims: To analyze the effect of behavioral contagion regarding problematic
      adolescent alcohol use among countries with varying prevalence of problematic
      drinking. Methods: Nested data from 48,215 12 to 16-year olds from seventh to
      ninth grade of 25 European countries (48.5% male, M = 13.83 years) were studied
      using hierarchical general linear modeling sequences. Finally, an intercept-as
      outcome model was built to test the main hypothesis. Results: Multilevel analyses
      validated the significant effects of the individual risk factors of being older
      (OR = 2.02), being male (OR = 1.41) and being native born (OR = 1.32) on becoming
      a problematic alcohol user. Regarding the aggregated country-level predictor
      'proportion of problematic alcohol users', the effect of behavioral contagion was
      also confirmed (OR = 1.05). Conclusions: The contagion effect regarding alcohol
      use behavior calls for a focus on environmental prevention efforts. By decreasing
      the public acceptance of (adolescent) alcohol use, the average proportion of
      problematic adolescent alcohol users in European countries may be reduced.

PMID- 29016724
TI  - Triggered intracellular calcium waves in dog and human left atrial myocytes from
      normal and failing hearts.
AB  - Aims: Abnormal intracellular Ca2+ cycling contributes to triggered activity and
      arrhythmias in the heart. We investigated the properties and underlying
      mechanisms for systolic triggered Ca2+ waves in left atria from normal and
      failing dog hearts. Methods and results: Intracellular Ca2+ cycling was studied
      using confocal microscopy during rapid pacing of atrial myocytes (36  degrees C)
      isolated from normal and failing canine hearts (ventricular tachypacing model).
      In normal atrial myocytes (NAMs), Ca2+ waves developed during rapid pacing at
      rates >= 3.3 Hz and immediately disappeared upon cessation of pacing despite high
      sarcoplasmic reticulum (SR) load. In heart failure atrial myocytes (HFAMs),
      triggered Ca2+ waves (TCWs) developed at a higher incidence at slower rates.
      Because of their timing, TCW development relies upon action potential (AP)-evoked
      Ca2+ entry. The distribution of Ca2+ wave latencies indicated two populations of
      waves, with early events representing TCWs and late events representing
      conventional spontaneous Ca2+ waves. Latency analysis also demonstrated that TCWs
      arise after junctional Ca2+ release has occurred and spread to non-junctional
      (cell core) SR. TCWs also occurred in intact dog atrium and in myocytes from
      humans and pigs. beta-adrenergic stimulation increased Ca2+ release and abolished
      TCWs in NAMs but was ineffective in HFAMs making this a potentially effective
      adaptive mechanism in normals but potentially arrhythmogenic in HF. Block of Ca
      calmodulin kinase II also abolished TCWs, suggesting a role in TCW formation.
      Pharmacological manoeuvres that increased Ca2+ release suppressed TCWs as did
      interventions that decreased Ca2+ release but these also severely reduced
      excitation-contraction coupling. Conclusion: TCWs develop during the atrial AP
      and thus could affect AP duration, producing repolarization gradients and
      creating a substrate for reentry, particularly in HF where they develop at slower
      rates and a higher incidence. TCWs may represent a mechanism for the initiation
      of atrial fibrillation particularly in HF.

PMID- 29016727
TI  - Soft tissue treatment changes with fixed functional appliances and with maxillary
      premolar extraction in Class II division 1 malocclusion patients.
AB  - Objective: The aim of this study was to compare the soft tissue changes and post
      treatment status after complete fixed functional appliance non-extraction and
      maxillary premolar extraction treatment in patients with Class II division 1
      malocclusion. Materials/methods: The sample consisted of 96 lateral cephalograms
      of 48 patients, divided into two groups. Group 1 consisted of 23 patients treated
      with fixed functional appliance associated with fixed appliances, with initial
      and final mean ages of 12.71 and 15.16 years, respectively, mean treatment time
      of 2.44 years and initial mean overjet of 6.83 mm. Group 2 comprised 25 patients
      treated with extraction of two maxillary premolars with initial and final mean
      ages of 13.05 and 15.74 years, respectively, mean treatment time of 2.67 years
      and initial mean overjet of 7.01 mm. t-Tests were used to compare treatment
      changes and the final cephalometric statuses between the groups. Results:
      According to the results, there was no inter-group difference regarding the soft
      tissue changes and post-treatment status. Limitations: The use of exclusively one
      type of fixed functional appliance in group 1 and performance of only one type of
      mechanics during space closure in group 2 were not always possible. Conclusion:
      Late pubertal patients with Class II division 1 malocclusion treated with fixed
      functional appliances associated with fixed appliances present similar soft
      tissue results as two-maxillary premolar extraction treatments.

PMID- 29016726
TI  - Genetic Polymorphisms of Alcohol Metabolizing Enzymes and Alcohol Consumption are
      Associated With Asymptomatic Cardiac Remodeling and Subclinical Systolic
      Dysfunction in Large Community-Dwelling Asians.
AB  - Aims: Excessive consumption of alcoholic beverages is associated with cardiac
      remodeling and cardiomyopathy. We examined the possible association of alcohol
      use, common Asian genetic variants in genes involved in alcohol metabolism, and
      cardiac structures/functions alterations. Methods: A prospective, community
      dwelling survey among individuals with available complete echocardiography
      examined the associations of alcohol use, cardiac structure/functions, and three
      common alcohol metabolizing genetic variants, including aldehyde dehydrogenase 2
      (ALDH2), alcohol dehydrogenase 1B (ADH1B) and cytochrome P450 (CYP) isoform 2E1
      (CYP2E1). Results: Among 1577 participants (mean age: 53 +/- 9, 59.7% female), we
      observed that in subjects with more frequent weekly ethanol intake showed greater
      left ventricle (LV) mass, more impaired diastolic functions, and reduced global
      longitudinal strain (GLS), systolic (SRs) and early diastolic strain rates (SRe)
      (P<0.05). After propensity matching for clinical confounders (n = 330:30 for
      frequent users and non-users), frequent alcohol use and subjects carrying ALDH2
      (A/G or A/A), ADH1B (A/A) or CYP2E1(T/C or T/T) polymorphisms were all associated
      with worse GLSRs and GLSRe, with combined alcohol use and any given genetic
      variant aggravated these associations (all P < 0.05). Finally, we observed Gene
      Gene synergistic effects on LV functional decline in frequent alcohol users by
      using linear mixed effect model (all interaction P < 0.05). Conclusions: Among
      East Asians, even moderate alcohol consumption can confer subclinical adverse
      effects on cardiac systolic functions, which was most pronounced in subjects
      carrying common variants in alcohol metabolizing genes. These findings challenge
      the notion of beneficial influences of less heavy ethanol consumption on the
      heart, especially among East Asians. Short summary: This study evaluated the
      association of level of alcohol consumption and genetic variants in genes
      involved in alcohol metabolism with changes in cardiac function in East Asians.
      Even moderate alcohol use conferred subclinical adverse effects on cardiac
      systolic functions, which were most pronounced in subjects carrying common
      alcohol metabolizing genes.

PMID- 29016728
TI  - Augmented Th17 differentiation in Trim21 deficiency promotes a stable phenotype
      of atherosclerotic plaques with high collagen content.
AB  - Aims: Patients with hyperlipidemia are at risk of atherosclerosis, but not all
      develop cardiovascular disease, highlighting the importance of other risk factors
      such as inflammation. Both the innate and adaptive arms of the immune system have
      been suggested in the initiation and propagation of plaque formation. Tri-partite
      motif (TRIM) 21 is a regulator of tissue inflammation and pro-inflammatory
      cytokine production, and has been implicated in chronic inflammatory disease.
      Here, we investigate a potential role for TRIM21 in coronary artery disease.
      Methods and results: Trim21-deficient or wild-type bone marrow was transplanted
      into Ldlr-/- mice fed a hypercholesterolemic diet. The Trim21-/-->Ldlr-/- mice
      developed larger atherosclerotic plaques, with significantly higher collagen
      content compared to mice transplanted with wild-type cells. High collagen content
      of the atheroma is stabilizing, and has recently been linked to IL-17.
      Interestingly, Trim21-/-->Ldlr-/- mice had elevated CD4 and IL-17 mRNA expression
      in plaques, and increased numbers of activated CD4+ T cells in the periphery. An
      increased differentiation of naive T cells lacking Trim21 into Th17 cells was
      confirmed in vitro, with transcriptomic analysis revealing upregulation of genes
      of a non-pathogenic Th17 phenotype. Also, decreased expression of matrix
      metalloproteinases (MMPs) was noted in aortic plaques. Analysis of human carotid
      plaques confirmed that TRIM21 expression negatively correlates with the
      expression of key Th17 genes and collagen, but positively to MMPs also in
      patients, linking our findings to a clinical setting. Conclusion: In this study,
      we demonstrate that TRIM21 influences atherosclerosis via regulation of Th17
      responses, with TRIM21 deficiency promoting IL-17 expression and a more fibrous,
      stable, phenotype of the plaques.

PMID- 29016729
TI  - Influence of self-esteem on perceived orthodontic treatment need and oral health
      related quality of life in children: the Generation R Study.
AB  - Background: Self-esteem (SE) is suggested to influence the relationship between
      orthodontic treatment need and oral health-related quality of life (OHRQoL), but
      evidence lacks. The aim of the present study was to investigate SE in the
      relationship between subjective orthodontic need and OHRQoL in children. Methods:
      This cross-sectional study was embedded in the Generation R Study, a multi-ethnic
      population-based cohort. In total, 3796 10-year old children participated in the
      present study. OHRQoL, measured with the Child Oral Health Impact Profile-ortho,
      and subjective orthodontic need were assessed within parental questionnaires. SE
      was measured with a modified version of the Harter's self-perception profile
      rated by the children. The role of SE in the association between SOT and OHRQoL
      was evaluated with linear regression models. Furthermore, the difference in this
      association between children with high and low SE was investigated. Results:
      Higher subjective orthodontic need was associated with lower OHRQoL scores
      (borderline: beta [95% CI] = -0.55 [-0.77, -0.33]; definite: -1.65 [-1.87, 
      1.54]). Children with lower SE scores showed a stronger relationship between
      borderline and definite subjective orthodontic need with OHRQoL (beta [95% CI] = 
      0.56 [-0.81, -0.31] respectively -1.68 [-1.94, -1.42]) than children with higher
      SE scores did (beta [95% CI] = -0.51 [-0.97, -0.04] respectively -1.43 [-1.90, 
      0.95]). Conclusion: The relationship between subjective orthodontic need and
      OHRQoL is not based on the SE of children. However, SE modifies the relationship
      between subjective orthodontic need and OHRQoL. Work still needs to be done to
      find an explanation for the effect modification by SE in the relationship between
      subjective health perceptions and OHRQoL.

PMID- 29016730
TI  - MicroRNA-424(322) as a new marker of disease progression in pulmonary arterial
      hypertension and its role in right ventricular hypertrophy by targeting SMURF1.
AB  - Aims: MicroRNAs (miRNAs) have been implicated in the pathogenesis of pulmonary
      hypertension (PH), a multifactorial and progressive condition associated with an
      increased afterload of the right ventricle leading to heart failure and death.
      The main aim of this study was to correlate the levels of miR-424(322) with the
      severity and prognosis of PH and with right ventricle hypertrophy progression.
      Additionally, we intended to evaluate the mechanisms and signalling pathways
      whereby miR-424(322) secreted by pulmonary arterial endothelial cells (PAECs)
      impacts cardiomyocytes. Methods and results: Using quantitative real-time PCR, we
      showed that the levels of circulating miR-424(322) are higher in PH patients when
      compared with healthy subjects. Moreover, we found that miR-424(322) levels
      correlated with more severe symptoms and haemodynamics. In the subgroup of
      Eisenmenger syndrome patients, miR-424(322) displayed independent prognostic
      value. Furthermore, we demonstrated that miR-424(322) targets SMURF1, through
      which it sustains bone morphogenetic protein receptor 2 signalling. Moreover, we
      showed that hypoxia induces the secretion of miR-424(322) by PAECs, which after
      being taken up by cardiomyocytes leads to down-regulation of SMURF1. In the
      monocrotaline rat model of PH, we found an association between circulating miR
      424(322) levels and the stage of right ventricle hypertrophy, as well as an
      inverse correlation between miR-424(322) and SMURF1 levels in the hypertrophied
      right ventricle. Conclusions: This study shows that miR-424(322) has diagnostic
      and prognostic value in PH patients, correlating with markers of disease
      severity. Additionally, miR-424(322) can target proteins with a direct effect on
      heart function, suggesting that this miRNA can act as a messenger linking
      pulmonary vascular disease and right ventricle hypertrophy.

PMID- 29016731
TI  - Electrical coupling between ventricular myocytes and myofibroblasts in the
      infarcted mouse heart.
AB  - Aims: Recent studies have demonstrated electrotonic coupling between scar tissue
      and the surrounding myocardium in cryoinjured hearts. However, the electrical
      dynamics occurring at the myocyte-nonmyocyte interface in the fibrotic heart
      remain undefined. Here, we sought to develop an assay to interrogate the
      nonmyocyte cell type contributing to heterocellular coupling and to characterize,
      on a cellular scale, its voltage response in the infarct border zone of living
      hearts. Methods and results: We used two-photon laser scanning microscopy in
      conjunction with a voltage-sensitive dye to record transmembrane voltage changes
      simultaneously from cardiomyocytes and adjoined nonmyocytes in Langendorff
      perfused mouse hearts with healing myocardial infarction. Transgenic mice with
      cardiomyocyte-restricted expression of a green fluorescent reporter protein
      underwent permanent coronary artery ligation and their hearts were subjected to
      voltage imaging 7-10 days later. Reporter-negative cells, i.e. nonmyocytes, in
      the infarct border zone exhibited depolarizing transients at a 1:1 coupling ratio
      with action potentials recorded simultaneously from adjacent, reporter-positive
      ventricular myocytes. The electrotonic responses in the nonmyocytes exhibited
      slower rates of de- and repolarization compared to the action potential waveform
      of juxtaposed myocytes. Voltage imaging in infarcted hearts expressing a
      fluorescent reporter specifically in myofibroblasts revealed that the latter were
      electrically coupled to border zone myocytes. Their voltage transient properties
      were indistinguishable from those of nonmyocytes in hearts with cardiomyocyte
      restricted reporter expression. The density of connexin43 expression at
      myofibroblast-cardiomyocyte junctions was ~5% of that in the intercalated disc
      regions of paired ventricular myocytes in the remote, uninjured myocardium,
      whereas the ratio of connexin45 to connexin43 expression levels at heterocellular
      contacts was ~1%. Conclusion: Myofibroblasts contribute to the population of
      electrically coupled nonmyocytes in the infarct border zone. The slower kinetics
      of myofibroblast voltage responses may reflect low electrical conductivity across
      heterocellular junctions, in accordance with the paucity of connexin expression
      at myofibroblast-cardiomyocyte contacts.

PMID- 29016734
TI  - The impact of Cone Beam CT on financial costs and orthodontists' treatment
      decisions in the management of maxillary canines with eruption disturbance.
AB  - Background: Examination with Cone Beam CT (CBCT) is common for localizing
      maxillary canines with eruption disturbance. The benefits and costs of these
      examinations are unclear. Objectives: To measure: 1. the proportion of
      orthodontists' treatment decisions that were different based on intraoral and
      panoramic radiography (M1) compared with CBCT and panoramic radiography (M2); and
      2. the costs of producing different treatment plans, regarding patients with
      maxillary canines with eruption disturbance. Subjects and methods: Orthodontists
      participated in a web-based survey and were randomly assigned to denote treatment
      decisions and the level of confidence in this decision for four patient cases
      presented with M1 or M2 at two occasions for the same patient case. Results: One
      hundred and twelve orthodontists made 445 assessments based on M1 and M2,
      respectively. Twenty-four per cent of the treatment decisions were different
      depending on which method the raters had access to, whereof one case differed
      significantly from all other cases. The mean total cost per examination was
      ?99.84 using M1 and ?134.37 using M2, resulting in an incremental cost per
      examination of ?34.53 for M2. Limitations: Benefits in terms of number of
      different treatment decisions must be considered as an intermediate outcome for
      the effectiveness of a diagnostic method and should be interpreted with caution.
      Conclusions: For the patient cases presented in this study, most treatment
      decisions were the same irrespective of radiological method. Accordingly, this
      study does not support routine use of CBCT regarding patients with maxillary
      canine with eruption disturbance.

PMID- 29016732
TI  - Regulation of vascular smooth muscle cell calcification by syndecan-4/FGF
      2/PKCalpha signalling and cross-talk with TGFbeta.
AB  - Aims: Vascular calcification is a major cause of morbidity and mortality.
      Fibroblast growth factor-2 (FGF-2) plays an instructive role in osteogenesis and
      bone development, but its role in vascular calcification was unknown. Therefore,
      we investigated the involvement of FGF-2 in vascular calcification and determined
      the mechanism by which it regulates this process. Methods and results: We
      demonstrate that FGF-2 expression is increased in vascular smooth muscle cells
      (VSMCs) induced to deposit a mineralized matrix by incubation with beta
      glycerophosphate. FGF-2 is also localized to sites of calcification within human
      atherosclerotic plaques. The expression of syndecan-4, a heparan sulfate
      proteoglycan which regulates FGF-2 signalling, is also increased in mineralizing
      VSMCs and co-localizes with FGF-2 in human calcified atherosclerotic plaques.
      Exogenous FGF-2 inhibits VSMC mineralization, and this inhibition is reduced when
      syndecan-4 expression is knocked-down using siRNA. Biochemical inhibition of FGFR
      signalling using a pan FGFR inhibitor (BGJ398) or knocking-down syndecan-4
      expression in VSMCs using siRNA increases VSMC mineralization. These increases
      are prevented by inhibiting transforming growth factor-beta (TGFbeta) signalling
      with SB431542, suggesting cross-talk between FGF-2 and TGFbeta signalling is
      crucial for the regulation of VSMC mineralization. Syndecan-4 can also regulate
      FGF-2 signalling directly via protein kinase Calpha (PKCalpha) activation.
      Biochemical inhibition of PKCalpha activity using Go6976, or siRNA-mediated
      suppression of PKCalpha expression increases VSMC mineralization; this increase
      is also prevented with SB431542. Finally, the ability of FGF-2 to inhibit VSMC
      mineralization is reduced when PKCalpha expression is knocked-down. Conclusion:
      This is the first demonstration that syndecan-4 promotes FGF-2 signalling, and in
      turn, suppresses VSMC mineralization by down-regulating TGFbeta signalling. Our
      discoveries that FGF-2 and syndecan-4 expression is increased in mineralizing
      VSMCs and that PKCalpha regulates FGF-2 and TGFbeta signalling in VSMCs suggests
      that the syndecan-4/FGF-2/TGFbeta signalling axis could represent a new
      therapeutic target for vascular calcification.

PMID- 29016735
TI  - LncRNA TUG1 sponges miR-204-5p to promote osteoblast differentiation through
      upregulating Runx2 in aortic valve calcification.
AB  - Aims: Emerging evidence indicates that long non-coding RNAs (lncRNAs) play a
      vital role in cardiovascular physiology and pathology. Although the lncRNA TUG1
      is implicated in atherosclerosis, its function in calcific aortic valve disease
      (CAVD) remains unknown. Methods and results: In this study, we found that TUG1
      was highly expressed in human aortic valves and primary valve interstitial cells
      (VICs). Moreover, TUG1 knockdown induced inhibition of osteoblast differentiation
      in CAVD both in vitro and in vivo. Mechanistically, silencing of TUG1 increased
      the expression of miR-204-5p and subsequently inhibited Runx2 expression at the
      post-transcriptional level. Importantly, TUG1 directly interacted with miR-204-5p
      and downregulation of miR-204-5p efficiently reversed the suppression of Runx2
      induced by TUG1 short hairpin RNA (shRNA). Thus, TUG1 positively regulated the
      expression of Runx2, through sponging miR-204-5p, and promoted osteogenic
      differentiation in CAVD. Conclusion: All together, the evidence generated by our
      study elucidates the role of lncRNA TUG1 as a miRNA sponge in CAVD, and sheds new
      light on lncRNA-directed diagnostics and therapeutics in CAVD.

PMID- 29016736
TI  - Long-term (>=15 years) post-treatment changes and outcome quality after Class
      II:1 treatment in comparison to untreated Class I controls.
AB  - Aim: To investigate the long-term (>=15 years) post-treatment (Tx) occlusal
      changes and outcome quality after Class II:1 Tx. Subjects and Methods: Herbst-MBA
      Tx had been performed at age 12.8 +/- 2.7 years in 119 patients. A recall was
      conducted and study models from before and after active Tx, after retention as
      well as after recall were evaluated using standard occlusal variables and the PAR
      index. These data were compared to 31 untreated Class I controls. Results: 52 out
      of 119 patients could be located and participated at 33.6 +/- 3.1 years. Compared
      to the 67 patients who did not participate in the recall, the pre- and post-Tx
      occlusal data of the participants did not differ systematically; however, the PAR
      scores were higher by 3.0-4.7 points at all times. Pre-Tx, the mean values of the
      52 participants were: PAR = 27.2 +/- 7.6, Class II molar relationship (MR) = 0.7
      cusp widths (cw), overjet = 8.2 mm, overbite = 4.1 mm. After Tx, the PAR score
      was 3.4 +/- 2.2. A Class I MR (0.0 +/- 0.1 cw) with normal overjet (2.3 +/- 0.7
      mm) and overbite (1.3 +/- 0.7 mm) existed. At recall, a mild PAR score increase
      to 8.2 +/- 5.5 points had occurred; this was mainly due to increased overjet and
      overbite values (3.6 +/- 1.1 and 2.8 +/- 1.6 mm) while the MR was stable (0.0 +/-
      0.2 cw). For all these variables, similar findings were made in the untreated
      controls. Conclusion: The occlusal outcome of Class II:1 Tx showed very good long
      term stability. While mild changes occur post-Tx, the long-term result is similar
      to untreated Class I controls.

PMID- 29016737
TI  - Diverging effects of enalapril or eplerenone in primary prevention against
      doxorubicin-induced cardiotoxicity.
AB  - Aims: Clinical studies suggest beneficial effects of renin-angiotensin system
      blockade for prevention of left ventricular (LV) dysfunction after chemotherapy.
      However, the efficacy of this strategy as primary prevention has been poorly
      studied. This study aimed at identifying the pathophysiological mechanisms by
      which mineralocorticoid receptor antagonism (MRA) or angiotensin converting
      enzyme inhibition (ACEi) provide protection against doxorubicin-induced
      cardiotoxicity (DIC) in mouse models of acute and chronic toxicity. Methods and
      results: Acute DIC was induced by a single injection of Dox at 15 mg/kg and
      chronic DIC applied 5 injections of Dox at 4 mg/kg/week. MRA was achieved using
      eplerenone or cardiomyocyte-specific ablation of the MR gene in transgenic mice
      and ACEi using enalapril. Drugs were provided with the first dose of Dox and
      applied until the end of the study. In both model of DIC, Dox induced cardiac
      atrophy with decreased LV volume, reduced cardiomyocyte cell size, and cardiac
      dysfunction. In the acute model, neither MRA nor ACEi protected against these
      manifestations of DIC. In the chronic model, concomitant treatment with
      eplerenone did not protect against DIC and drastically increased plasma
      aldosterone levels and cardiac levels of angiotensin II type 1 receptor and of
      connective tissue growth factor (CTGF), as observed in acute DIC. Enalapril
      treatment in the chronic model, however, protected against cardiac dysfunction
      and cardiomyocyte atrophy and was associated with increased activation of the
      PI3K/AKT/mTOR pathway along with normal levels of CTGF. Conclusion: Enalapril and
      eplerenone disparately impact on cellular signalling in DIC. Eplerenone, on top
      of Dox treatment was not protective and associated with increased levels of
      plasma aldosterone and of cardiac CTGF. In contrast, we show that primary
      prevention with enalapril preserves LV morphology and function in a clinically
      relevant model of chronic DIC, with increased stimulation of the PI3K/AKT/mTOR
      axis and normal CTGF levels suggesting potential therapeutic implications.

PMID- 29016733
TI  - Endothelial to haematopoietic transition contributes to pulmonary arterial
      hypertension.
AB  - Aims: The pathogenic mechanisms of pulmonary arterial hypertension (PAH) remain
      unclear, but involve dysfunctional endothelial cells (ECs), dysregulated immunity
      and inflammation in the lung. We hypothesize that a developmental process called
      endothelial to haematopoietic transition (EHT) contributes to the pathogenesis of
      pulmonary hypertension (PH). We sought to determine the role of EHT in mouse
      models of PH, to characterize specific cell types involved in this process, and
      to identify potential therapeutic targets to prevent disease progression. Methods
      and results: When transgenic mice with fluorescence protein ZsGreen-labelled ECs
      were treated with Sugen/hypoxia (Su/Hx) combination to induce PH, the percentage
      of ZsGreen+ haematopoietic cells in the peripheral blood, primarily of myeloid
      lineage, significantly increased. This occurrence coincided with the depletion of
      bone marrow (BM) ZsGreen+ c-kit+ CD45- endothelial progenitor cells (EPCs), which
      could be detected accumulating in the lung upon PH-induction. Quantitative RT-PCR
      based gene array analysis showed that key transcription factors driving
      haematopoiesis were expressed in these EPCs. When transplanted into lethally
      irradiated recipient mice, the BM-derived EPCs exhibited long-term engraftment
      and haematopoietic differentiation capability, indicating these EPCs are
      haemogenic in nature. Specific inhibition of the critical haematopoietic
      transcription factor Runx1 blocked the EHT process in vivo, prevented egress of
      the BM EPCs and ultimately attenuated PH progression in Su/Hx- as well as in
      monocrotaline-induced PH in mice. Thus, myeloid-skewed EHT promotes the
      development of PH and inhibition of this process prevents disease progression in
      mouse models of PH. Furthermore, high levels of Runx1 expression were found in
      circulating CD34+ CD133+ EPCs isolated from peripheral blood of patients with PH,
      supporting the clinical relevance of our proposed mechanism of EHT. Conclusion:
      EHT contributes to the pathogenesis of PAH. The transcription factor Runx1 may be
      a novel therapeutic target for the treatment of PAH.

PMID- 29016738
TI  - Three-dimensional Frankfort horizontal plane for 3D cephalometry: a comparative
      assessment of conventional versus novel landmarks and horizontal planes.
AB  - Background: To assess the reproducibility of landmarks in three dimensions that
      determine the Frankfort horizontal plane (FH) as well as two new landmarks, and
      to evaluate the angular differences of newly introduced planes to the FH.
      Methods: Three-dimensional (3D) surface models were created from CBCT scans of 26
      dry human skulls. Porion (Po), orbitale (Or), internal acoustic foramen (IAF),
      and zygomatico-maxillary suture (ZyMS) were indicated in the software by three
      observers twice with a 4-week interval. Angles between two FHs (FH 1: Or-R, Or-L,
      mid-Po; FH 2: Po-R, Po-L, mid-Or) and between FHs and new planes (Plane 1-6) were
      measured. Coordinates were exported to a spreadsheet. A statistical analysis was
      performed to define the landmark reproducibility and 3D angles. Results: Intra-
      and inter-observer landmark reproducibility showed mean difference more than 1 mm
      for x-coordinates of all landmarks except IAF. IAF showed significantly better
      reproducibility than other landmarks (P < 0.0018). The mean angular difference
      between FH 1 and FH 2 was 0.7 degrees. Plane 3, connecting Or-R, Or-L and mid
      IAF, and Plane 4, connecting Po-R, Po-L and mid-ZyMS, both showed an angular
      difference of less than 1 degree when compared to FHs. Conclusions: This study
      revealed poor reproducibility of the traditional FH landmarks on the x-axis and
      good reproducibility of a new landmark tested to replace Po, the IAF. Yet, Or
      showed superior results compared to ZyMS. The potential of using new horizontal
      planes was demonstrated. Future studies should focus on identification of a valid
      alternative for Or and ZyMS and on clinical implementation of the findings.

PMID- 29016739
TI  - Association between severity of hypodontia and cephalometric skeletal patterns: a
      retrospective study.
AB  - Objective: To assess if severity of hypodontia is related to a specific skeletal
      pattern. Study design: Lateral cephalometric radiographs and dental panoramic
      tomographs of 182 hypodontia patients were analysed. The severity of hypodontia
      was recorded and the sample was divided into groups with mild (n = 71), moderate
      (n = 56) and severe (n = 55) hypodontia. According to ethnicity, the sample was
      further subdivided into White Caucasians, African-British, and Arabian/Indian
      subgroups. Cephalometric measurements were used to quantify the skeletal
      discrepancy and vertical facial dimensions. Mean and standard deviation for each
      group were obtained for comparison and an analysis of variance (ANOVA) was
      carried out to assess the level of significance between the means of the readings
      in different severity groups. Results: In the white Caucasian group, increased
      severity of hypodontia, was related to a retrusive maxilla with concomitant
      reduction of A point, Nasion, B point (ANB), reduced mandibular plane angle and
      anterior lower facial height (P value: 0.0935-0.9371). For the Black-British and
      Arabian/Indian groups' findings were inconsistent, with no specific pattern as
      the number of missing teeth increased. Conclusion: The white Caucasian group
      followed a pattern that has previously been reported in other studies. For Black
      British and Arabian/Indian groups' findings were inconsistent and no specific
      pattern emerged for different degrees of hypodontia.

PMID- 29016741
TI  - The effect of low-level laser therapy on orthodontically induced root resorption:
      a pilot double blind randomized controlled trial.
AB  - Background: The effect of low-level laser therapy (LLLT) on accelerating
      orthodontic tooth movement has been extensively studied; however, there is
      limited knowledge on the use of LLLT on orthodontic root resorption. Objective:
      To investigate the effect of LLLT on orthodontically induced inflammatory root
      resorption (OIIRR) and to compare the difference between pulsed and continuous
      LLLT on OIIRR. Trial design: Double-blind, single-centre 3-arm parallel split
      mouth randomized controlled trial. Participants: Twenty adolescent patients who
      required bilateral maxillary first premolar (MFP) orthodontic extractions were
      recruited from the Sydney Dental Hospital between October 2014 and December 2014.
      Intervention: All MFPs were tipped buccally for 28 days to induce OIIRR. The
      experimental premolars (n = 20) received LLLT and the control premolars (n = 20)
      received placebo-laser on days 0, 1, 2, 3, 7, 14, and 21. Ten experimental
      premolars received LLLT via continuous delivery and 10 received pulsed delivery.
      Laser parameter: AlGaAs diode laser of 808 nm wavelength, 0.18 W power, 1.6 J per
      point, and duration of 9s for continuous mode and 4.5 s for pulsed mode. Outcome:
      The difference in root resorption crater volume between LLLT and placebo-laser
      and continuous or pulsed laser delivery after 28 days. Randomization:
      Randomization was computer-generated, with allocation concealment by opaque
      sequentially numbered sealed envelopes. Blinding: The participants and operator
      were blinded. Results: Eighty-eight patients were screened and 20 patients were
      randomized. Forty premolars were analysed. LLLT resulted in 23 per cent less root
      resorption compared to the placebo (P = 0.026). Pulsed laser delivery resulted in
      5 per cent less root resorption than continuous; however, this was not
      statistically significant (P = 0.823). No harm was observed. Conclusion: Teeth
      treated with LLLT had less total root resorption than placebo-laser. Furthermore,
      there was minimal difference between pulsed or continuous delivery of LLLT. Trial
      Registration: Clinical Trials Registry (ACTRN12616000829415). Protocol: The
      protocol was not published before trial commencement.

PMID- 29016742
TI  - Looking Beyond Traditional Metrics in Orthodontics: An Altmetric Study on the
      Most Discussed Articles on the Web.
AB  - Objective: To evaluate the online visibility of the most popular orthodontic
      articles in Web platforms in relation to publication details and citations.
      Materials and Methods: Altmetric Explorer (Altmetric LLP, London, UK) was
      searched for articles published in 11 orthodontic journals without time limits in
      publication and citation on social media. The 200 articles with the highest
      Altmetric Attention Score (AAS) were collected and screened for data related to
      publication (date, journal, access), authorship (number of authors, affiliation
      and origin of the corresponding author), and research (type, subject, funding).
      Citation counts were harvested from Scopus. Results: The top 200 articles
      presented a median AAS of 8.0 (range: 5.0-196.0), and were mostly bookmarked in
      Mendeley (median: 16.6 references; range: 0-199.0). American Journal of
      Orthodontics & Dentofacial Orthopedics, European Journal of Orthodontics and The
      Angle Orthodontist contributed 86 per cent of the total number of research
      outputs. Studies investigating socio-demographics had significantly higher AAS
      compared to diagnostic studies (median AAS: 19.0; range: 7.0-34.0; versus median
      AAS: 6.0; range: 5.0-10.0. No other study parameter was found to be statistically
      significant. AAS did not correlate to the number of citations as reported in
      Scopus. Limitations: The early stage of altmetrics and their complementary role
      in assessing together with the citation-based metrics the research impact need to
      be acknowledged in the interpretation of the results. Conclusions: Visibility of
      orthodontic articles on the Web is not significantly correlated with citations.
      Studies on socio-demographics had significantly higher number of online mentions.
      More constructive online presence of orthodontic journals is needed to reinforce
      dissemination of research data among scholars and non-scholars.

PMID- 29016743
TI  - Semaphorin-3E attenuates neointimal formation via suppressing VSMCs migration and
      proliferation.
AB  - Aims: The migration and proliferation of vascular smooth muscle cells (VSMCs) are
      crucial events in the neointimal formation, a hallmark of atherosclerosis and
      restenosis. Semaphorin3E (Sema3E) has been found to be a critical regulator of
      cell migration and proliferation in many scenarios. However, its role on VSMCs
      migration and proliferation is unclear. This study aimed to investigate the
      effect of Sema3E on VSMCs migration, proliferation and neointimal formation, and
      explore possible mechanisms. Methods and results: We found that the expression of
      Sema3E was progressively decreased during neointimal formation in a carotid
      ligation model. H&E-staining showed lentivirus-mediated overexpression of Sema3E
      in carotid ligation area attenuated neointimal formation. Immunofluorescence
      staining showed that the receptor (PlexinD1) of Sema3E was expressed in vascular
      walls. In cultured mouse VSMCs, Sema3E inhibited VSMCs migration and
      proliferation via plexinD1 receptor. The inhibitory effect was mediated, at least
      in part, by inactivating Rap1-AKT signalling pathways in VSMCs. Moreover, we
      found that PDGFBB down-regulated the expression of Sema3E in VSMCs and Sema3E
      notably inhibited the expression of PDGFB in endothelial cells. In addition, the
      number of Sema3E-positive VSMCs was diminished in plaques of atherosclerotic
      patients. Results from a public GEO microarray database showed a negative
      correlation between Sema3E and PDGFB transcriptional levels in the human plaques
      examined. Conclusion: Our study demonstrates that Sema3E/plexinD1 inhibits
      proliferation and migration of VSMCs via inactivation of Rap1-AKT signalling
      pathways. The mutual inhibition between PDGF-BB and Sema3E after vascular injury
      plays a critical role in the process of neointimal formation.

PMID- 29016744
TI  - Effects of dapagliflozin on human epicardial adipose tissue: modulation of
      insulin resistance, inflammatory chemokine production, and differentiation
      ability.
AB  - Aims: In patients with cardiovascular disease, epicardial adipose tissue (EAT) is
      characterized by insulin resistance, high pro-inflammatory chemokines, and low
      differentiation ability. As dapagliflozin reduces body fat and cardiovascular
      events in diabetic patients, we would like to know its effect on EAT and
      subcutaneous adipose tissue (SAT). Methods and results: Adipose samples were
      obtained from 52 patients undergoing heart surgery. Sodium-glucose cotransporter
      2 (SGLT2) expression was determined by real-time polymerase chain reaction (n =
      20), western blot, and immunohistochemistry. Fat explants (n = 21) were treated
      with dapagliflozin and/or insulin and glucose transporters expression measured.
      Glucose, free fatty acid, and adipokine levels (by array) were measured in the
      EAT secretomes, which were then tested on human coronary endothelial cells using
      wound healing assays. Glucose uptake was also measured using the fluorescent
      glucose analogue (6NBDG) in differentiated stromal vascular cells (SVCs) from the
      fat pads (n = 11). Finally, dapagliflozin-induced adipocyte differentiation was
      assessed from the levels of fat droplets (AdipoRed staining) and of perilipin.
      SGLT2 was expressed in EAT. Dapagliflozin increased glucose uptake (20.95 +/- 4.4
      mg/dL vs. 12.97 +/- 4.1 mg/dL; P < 0.001) and glucose transporter type 4 (2.09 +/
      0.3 fold change; P < 0.01) in EAT. Moreover, dapagliflozin reduced the secretion
      levels of chemokines and benefited wound healing in endothelial cells (0.21 +/-
      0.05 vs. 0.38 +/- 0.08 open wound; P < 0.05). Finally, chronic treatment with
      dapagliflozin improved the differentiation of SVC, confirmed by AdipoRed staining
      [539 +/- 142 arbitrary units (a.u.) vs. 473 +/- 136 a.u.; P < 0.01] and perilipin
      expression levels (121 +/- 10 vs. 84 +/- 11 a.u.). Conclusions: Dapagliflozin
      increased glucose uptake, reduced the secretion of pro-inflammatory chemokines
      (with a beneficial effect on the healing of human coronary artery endothelial
      cells), and improved the differentiation of EAT cells. These results suggest a
      new protective pathway for this drug on EAT from patients with cardiovascular
      disease.

PMID- 29016746
TI  - Effects of low magnitude high frequency mechanical vibration combined with
      compressive force on human periodontal ligament cells in vitro.
AB  - Objective: Vibration can be used to accelerate tooth movement, though the exact
      mechanisms remain unclear. This study aimed to investigate the effects of low
      magnitude high frequency (LMHF) vibration combined with compressive force on
      periodontal ligament (PDL) cells in vitro. Materials and methods: Human PDL cells
      were isolated from extracted premolar teeth of four individuals. To determine the
      optimal frequency for later used in combination with compressive force, three
      cycles of low-magnitude (0.3 g) vibrations at various frequencies (30, 60, or 90
      Hz) were applied to PDL cells for 20 min every 24 h. To investigate the effects
      of vibration combined with compressive force, PDL cells were subjected to three
      cycles of optimal vibration frequency (V) or 1.5 g/cm2 compressive force for 48 h
      (C) or vibration combined with compressive force (VC). Cell viability was
      assessed using MTT assay. PGE2, soluble RANKL (sRANKL), and OPG production were
      quantified by ELISA. RANKL, OPG, and Runx2 expression were determined using real
      time PCR. Results: Cell viability was decreased in groups C and VC. PGE2 and
      RANKL, but not OPG, were increased in groups V, C, and VC, thus increasing the
      RANKL/OPG ratio. The highest level was observed in group VC. sRANKL was increased
      in groups V, C, and VC; however, no significant different between the
      experimental groups. Runx2 expression was reduced in groups C and VC.
      Conclusions: Vibration increased PGE2, RANKL, and sRANKL, but not OPG and Runx2.
      Vibration had the additive effects on PGE2 and RANKL, but not sRANKL in
      compressed PDL cells.

PMID- 29016740
TI  - A novel fibroblast growth factor-1 ligand with reduced heparin binding protects
      the heart against ischemia-reperfusion injury in the presence of heparin co
      administration.
AB  - Aims: Fibroblast growth factor 1 (FGF1), a heparin/heparan sulfate-binding growth
      factor, is a potent cardioprotective agent against myocardial infarction (MI).
      The impact of heparin, the standard of care for MI patients entering the
      emergency room, on cardioprotective effects of FGF1 is unknown, however. Methods
      and results: To address this, a rat model of MI was employed to compare
      cardioprotective potentials (lower infarct size and improve post-ischemic
      function) of native FGF1 and an engineered FGF1 (FGF1DeltaHBS) with reduced
      heparin-binding affinity when given at the onset of reperfusion in the absence or
      presence of heparin. FGF1 and FGF1DeltaHBS did not alter heparin's anticoagulant
      properties. Treatment with heparin alone or native FGF1 significantly reduced
      infarct size compared to saline (P < 0.05). Surprisingly, treatment with
      FGF1DeltaHBS markedly lowered infarct size compared to FGF1 (P < 0.05). Both
      native and modified FGF1 restored contractile and relaxation function (P < 0.05
      versus saline or heparin). Furthermore, FGF1DeltaHBS had greater improvement in
      cardiac function compared to FGF1 (P < 0.05). Heparin negatively impacted the
      cardioprotective effects (infarct size, post-ischemic recovery of function) of
      FGF1 (P < 0.05) but not of FGF1DeltaHBS. Heparin also reduced the biodistribution
      of FGF1, but not FGF1DeltaHBS, to the left ventricle. FGF1 and FGF1DeltaHBS bound
      and triggered FGFR1-induced downstream activation of ERK1/2 (P < 0.05); yet,
      heparin co-treatment decreased FGF1-produced ERK1/2 activation, but not that
      activated by FGF1DeltaHBS. Conclusion: These findings demonstrate that
      modification of the heparin-binding region of FGF1 significantly improves the
      cardioprotective efficacy, even in the presence of heparin, identifying a novel
      FGF ligand available for therapeutic use in ischemic heart disease.

PMID- 29016747
TI  - Five year trends (2008-2012) in cardiac implantable electrical device utilization
      in five European nations: a case study in cross-country comparisons using
      administrative databases.
AB  - Aims: Common methodologies for analysis of analogous data sets are needed for
      international comparisons of treatment and outcomes. This study tests using
      administrative hospital discharge (HD) databases in five European countries to
      investigate variation/trends in pacemaker (PM) and implantable cardioverter
      defibrillator (ICD) implant rates in terms of patient characteristics/management,
      device subtype, and initial implantation vs. replacement, and compares findings
      with existing literature and European Heart Rhythm Association (EHRA) reports.
      Methods and results: HD databases from 2008 to 2012 in Austria, England, Germany,
      Italy and Slovenia were interrogated to extract admissions (without patient
      identification) associated with PM and ICD implants and replacements, using
      direct cross-referencing of procedure codes and common methodology to compare
      aggregate data. 1 338 199 records revealed 212 952 PM and 62 567 ICD
      procedures/year on average for a 204.4 million combined population, a crude
      implant rate of about 104/100 000 inhabitants for PMs and 30.6 for ICDs. The
      first implant/replacement rate ratios were 81/24 (PMs) and 25/7 (ICDs). Rates
      have increased, with cardiac resynchronization therapy (CRT) subtypes for both
      devices rising dramatically. Significant between- and within-country variation
      persists in lengths of stay and rates (Germany highest, Slovenia lowest).
      Adjusting for age lessened differences for PM rates, scarcely affected ICDs.
      Male/female ratios remained stable at 56/44% (PMs) and 79/21% (ICDs). About 90%
      of patients were discharged to home; 85-100% were inpatient admissions.
      Conclusion: To aid in policymaking and track outcomes, HD administrative data
      provides a reliable, relatively cheap, methodology for tracking implant rates for
      PMs and ICDs across countries, as comparisons to EHRA data and the literature
      indicated.

PMID- 29016745
TI  - CXCL12-CXCR4 signalling plays an essential role in proper patterning of aortic
      arch and pulmonary arteries.
AB  - Aims: Chemokine CXCL12 (stromal derived factor 1: SDF1) has been shown to play
      important roles in various processes of cardiovascular development. In recent
      avian studies, CXCL12 signalling has been implicated in guidance of cardiac
      neural crest cells for their participation in the development of outflow tract
      and cardiac septum. The goal of this study is to investigate the extent to which
      CXCL12 signalling contribute to the development of aortic arch and pulmonary
      arteries in mammals. Methods and results: Novel Cxcl12-LacZ reporter and
      conditional alleles were generated. Using whole mount X-gal staining with the
      reporter allele and vascular casting techniques, we show that the domain
      branching pattern of pulmonary arteries in Cxcl12-null mice is completely
      disrupted and discordant with that of pulmonary veins and airways. Cxcl12-null
      mice also displayed abnormal and superfluous arterial branches from the aortic
      arch. The early steps of pharyngeal arch remodelling in Cxcl12-null mice appeared
      to be unaffected, but vertebral arteries were often missing and prominent
      aberrant arteries were present parallel to carotid arteries or trachea, similar
      to aberrant vertebral artery or thyroid ima artery, respectively. Analysis with
      computed tomography not only confirmed the results from vascular casting studies
      but also identified abnormal systemic arterial supply to lungs in the Cxcl12-null
      mice. Tie2-Cre mediated Cxcr4 deletion phenocopied the Cxcl12-null phenotypes,
      indicating that CXCR4 is the primary receptor for arterial patterning, whereas
      Cxcl12 or Cxcr4 deletion by Wnt1-Cre did not affect aortic arch patterning.
      Conclusion: CXCL12-CXCR4 signalling is essential for the correct patterning of
      aortic arches and pulmonary arteries during development. Superfluous arteries in
      Cxcl12-null lungs and the aortic arch infer a role of CXCL12 in protecting
      arteries from uncontrolled sprouting during development of the arterial system.

PMID- 29016748
TI  - The second generation cryoballoon has improved durable isolation of left but not
      right pulmonary veins: new insights from a multicentre study.
AB  - Aims: Pulmonary vein isolation (PVI) using second-generation cryoballoon (CB2) is
      associated with improved outcomes compared with first generation (CB1). We aimed
      at investigating the characteristics of left and right PV reconnections after CB1
      and CB2 ablations in patients with clinical recurrences requiring redo ablation.
      Methods and results: From 2010 to 2016, 776 patients underwent 28-mm cryoballoon
      PVI for symptomatic paroxysmal atrial fibrillation (AF) in 3 centres, 279 with
      CB1 and 497 with CB2. Among them, 94 patients (12.1%) had symptomatic AF
      recurrences requiring a redo ablation [43 (15.4%) CB1 and 51 (10.3%) CB2]. The
      benefit of CB2 over CB1 was compared for each PV. Durable PVI was confirmed in 7
      CB1 (16.3%) and 14 CB2 (27.4%) patients, and 2.7 +/- 2.1 and 1.4 +/- 1.4 gaps per
      patient were found, respectively (P = 0.002). Significantly more left superior
      and left inferior PVs were found to be isolated in CB2 compared with CB1 group
      (78.4% vs. 48.8%, P = 0.005 and 78.4% vs. 46.5%, P = 0.003, respectively) while
      the rate of durable right superior and right inferior PVs isolation were similar
      (68.6% vs. 60.5%, P = 0.542 and 66.7% vs. 55.8%, P = 0.387, respectively).
      Significantly fewer gaps were found in left PVs in CB2 patients, while there was
      no significant difference for right PVs. Gaps localization was similar in both
      groups. Conclusion: Fewer reconnection gaps are observed during redo ablations of
      paroxysmal AF in patients primarily ablated with CB2. This difference is driven
      by less reconnection gaps observed in both left PVs, while no difference was
      observed for right PVs.

PMID- 29016750
TI  - Electroanatomical mapping of coronary artery anatomy to guide epicardial
      ventricular tachycardia ablation.

PMID- 29016751
TI  - Cardiac effects of SGLT2 inhibitors: the sodium hypothesis.
AB  - The effects of intense glycaemic control on macrovascular complications in
      patients with type 2 diabetes are incompletely resolved, and many glucose
      lowering medications negatively affect cardiovascular outcomes. Recently, the
      EMPA-REG OUTCOME trial revealed that empagliflozin, an inhibitor of the sodium
      glucose cotransporter 2 (SGLT2), substantially reduced the risk of
      hospitalization for heart failure, death from cardiovascular causes, and all
      cause mortality in patients with type 2 diabetes mellitus at high cardiovascular
      risk. Although several mechanisms may explain this benefit, plasma volume
      contraction and a metabolic switch favouring cardiac ketone bodies oxidation have
      recently been proposed as the major drivers. Recent experimental work has
      prompted a novel and intriguing hypothesis, according to which empagliflozin may
      reduce intracellular sodium (Na+) load observed in failing cardiac myocytes by
      inhibiting the sarcolemmal Na+/H+ exchanger. Since elevated intracellular Na+
      hampers mitochondrial Ca2+ handling and thereby, deteriorates energy supply and
      demand matching and the mitochondrial antioxidative defence systems,
      empagliflozin may positively affect cardiac function by restoring mitochondrial
      function, and redox state in the failing heart. Here, we review the current
      evidence for such a third mechanistic hypothesis, which may foster heart failure
      and diabetes research into a new direction which harbours several potential
      targets for therapeutic intervention.

PMID- 29016752
TI  - Hypothyroidism and congenital long QT: additive effect causing torsades?

PMID- 29016753
TI  - Clinical impact, safety, and accuracy of the remotely monitored implantable loop
      recorder Medtronic Reveal LINQTM.
AB  - Aims: Implantable loop recorders (ILR) are indicated in a variety of clinical
      situations when extended cardiac rhythm monitoring is needed. We aimed to assess
      the clinical impact, safety, and accuracy of the new Medtronic Reveal LINQTM ILR
      that can be inserted outside the electrophysiology (EP) laboratory and remotely
      monitored. Methods and results: All 154 consecutive patients (100 males, 63 +/-
      15 year-old) who received the Reveal LINQTM ILR during the period July 2014-June
      2016 were enrolled. The device was implanted in a procedure room and all patients
      where provided with the MyCareLinkTM remote monitoring system. Data were reviewed
      every working day via the Carelink(r) web system by a specialist nurse who, in
      case of significant events, consulted an electrophysiologist. During a mean
      follow-up of 12.1 (6.7-18.4) months (range 2-24 months), a diagnosis was made in
      99 (64%) patients and in 60 (39%) >=1 therapeutic interventions were established
      following recording of arrhythmias. In 26 of these 60 patients, remote monitoring
      prompted therapeutic interventions following asymptomatic arrhythmic events 3.8
      months before the next theoretical scheduled in-office data download. False
      bradycardia detection for undersensing occurred in 44 (29%) patients and false
      tachycardia detection for oversensing in 4 (3%). One patient experienced skin
      erosion requiring explantation and none suffered from infection. Conclusion: The
      remote monitoring feature of the Reveal LINQTM allowed earlier diagnosis of
      asymptomatic but serious arrhythmias in a significant proportion of patients.
      Implantation of the device outside the EP laboratory appeared safe. However, R
      wave undersensing and consequent false recognition of bradyarrhythmias remains a
      clinically important technical issue.

PMID- 29016749
TI  - Differential eNOS-signalling by platelet subpopulations regulates adhesion and
      aggregation.
AB  - Aims: In addition to maintaining haemostasis, circulating blood platelets are the
      cellular culprits that form occlusive thrombi in arteries and veins. Compared to
      blood leucocytes, which exist as functionally distinct subtypes, platelets are
      considered to be relatively simple cell fragments that form vascular system plugs
      without a differentially regulated cellular response. Hence, investigation into
      platelet subpopulations with distinct functional roles in haemostasis/thrombosis
      has been limited. In our present study, we investigated whether functionally
      distinct platelet subpopulations exist based on their ability to generate and
      respond to nitric oxide (NO), an endogenous platelet inhibitor. Methods and
      results: Utilizing highly sensitive and selective flow cytometry protocols, we
      demonstrate that human platelet subpopulations exist based on the presence and
      absence of endothelial nitric oxide synthase (eNOS). Platelets lacking eNOS
      (approximately 20% of total platelets) fail to produce NO and have a down
      regulated soluble guanylate cyclase-protein kinase G (sGC-PKG)-signalling
      pathway. In flow chamber and aggregation experiments eNOS-negative platelets
      primarily initiate adhesion to collagen, more readily activate integrin
      alphaIIbbeta3 and secrete matrix metalloproteinase-2, and form larger aggregates
      than their eNOS-positive counterparts. Conversely, platelets having an intact
      eNOS-sGC-PKG-signalling pathway (approximately 80% of total platelets) form the
      bulk of an aggregate via increased thromboxane synthesis and ultimately limit its
      size via NO generation. Conclusion: These findings reveal previously unrecognized
      characteristics and complexity of platelets and their regulation of
      adhesion/aggregation. The identification of platelet subpopulations also has
      potentially important consequences to human health and disease as impaired
      platelet NO-signalling has been identified in patients with coronary artery
      disease.

PMID- 29016755
TI  - Outcomes after catheter ablation and cardioversion in patients with non-valvular
      atrial fibrillation: results from the prospective, observational XANTUS study.
AB  - Aims: In patients with atrial fibrillation, catheter ablation and cardioversion
      carry a risk of peri-procedural thromboembolic events; current guidelines
      recommend anticoagulation in these settings. This study aimed to report the
      baseline demographics and clinical characteristics of patients enrolled in the
      prospective, observational XANTUS study who underwent catheter ablation or
      cardioversion, and adverse outcomes with each of these procedures in patients
      treated with rivaroxaban. Methods and results: Data collected included
      information on catheter ablation and cardioversion, and adverse outcomes
      occurring within 30 days of these procedures: incidence of treatment-emergent
      adjudicated symptomatic thromboembolic events and major bleeding; and
      cardiovascular and all-cause death. Incidence of these adverse outcomes at 42
      days after cardioversion was also analysed. Patients undergoing either procedure
      had significantly lower mean CHA2DS2-VASc and HAS-BLED scores than those who did
      not, and were more frequently hospitalized at study baseline. Within a period of
      30 days after intervention, symptomatic thromboembolic events were reported in
      1.2% and 0.6% of patients undergoing ablation or cardioversion, respectively;
      major bleeding events were reported in 2.9% and 0.4% of patients undergoing
      ablation or cardioversion, respectively. No patients died within 30 days of
      intervention. Incidence of symptomatic thromboembolic and major bleeding events
      remained low at 42 days after cardioversion. Conclusion: Similar to the results
      of prospective and non-interventional studies, the low rates of symptomatic
      thromboembolic events and major bleeding in patients with atrial fibrillation
      undergoing ablation or cardioversion and treated with rivaroxaban in XANTUS
      suggest that its use is associated with an acceptable benefit-risk profile in
      this setting. Trial registration number: Clinicaltrials.gov: NCT01606995.

PMID- 29016757
TI  - Association of left atrial low-voltage area and thromboembolic risk in patients
      with atrial fibrillation.
AB  - Aims: Atrial fibrillation (AF) is associated with thromboembolic events.
      Currently, the CHA2DS2-VASc score is recommended for thromboembolic risk
      stratification in non-valvular AF patients. However, recent data suggested a
      potential role of atrial remodelling on thromboembolism. This study aimed to
      assess the association between left atrial low-voltage area (LVA) and history of
      clinical manifest as well as subclinical silent cerebral ischaemia (SCI) in AF
      patients. Methods and results: Two-hundred patients [64 +/- 10.5 years, 75 women
      (37.5%)] with symptomatic paroxysmal (n = 88, 44%) or persistent AF undergoing
      pulmonary vein isolation (PVI) were prospectively enrolled. Left atrial LVA
      (bipolar voltage < 0.5mV) was evaluated by intra-procedural mapping (>300 points
      per patient) during sinus rhythm. Cerebral delayed-enhancement magnetic resonance
      imaging was performed after PVI for detection of pre-existing procedural
      independent SCI. Over all, 17 patients (8.5%) had previous history of stroke. Pre
      existing SCIs were detected in 135 patients (67.5%). Patients with previous
      stroke (4.0 +/- 1.5 vs. 2.1 +/- 1.3, P < 0.0001) and pre-existing SCI (2.7 +/-
      1.3 vs. 1.5 +/- 1.4, P < 0.0001) had a significantly higher CHA2DS2-VASc score.
      LVA was significantly larger in patients with previous stroke (12.5 +/- 8.5% vs.
      3.4 +/- 5.4%, P < 0.0001) as well as pre-existing SCI (5.8 +/- 6.9% vs. 0.8 +/-
      1.7%, P < 0.0001). Multivariate regression analysis revealed that LVA was
      independently associated with the presence of SCI [hazard ratio (HR) per 1% LVA
      1.13 (1.06-1.22), P = 0.0003] and history of stroke [HR per 1% LVA 1.36 (1.19
      1.60), P < 0.0001] after adjustment of CHA2DS2-VASc score. Conclusion: Left
      atrial LVA is associated with history of stroke and SCI in patients with non
      valvular AF and might improve thromboembolic risk stratification after
      confirmation of its predictive value in future studies.

PMID- 29016756
TI  - The electrocardiogram as a predictor of successful pharmacological cardioversion
      and progression of atrial fibrillation.
AB  - Aims: Non-invasive characterization of atrial fibrillation (AF) substrate
      complexity based on the electrocardiogram (ECG) may improve outcome prediction in
      patients receiving rhythm control therapies for AF. Multiple parameters to assess
      AF complexity and predict treatment outcome have been suggested. A comparative
      study of the predictive performance of complexity parameters on response to
      therapy and progression of AF in a large patient population is needed to
      standardize non-invasive analysis of AF. Methods and results: A large variety of
      ECG complexity parameters were systematically compared in patients with recent
      onset AF undergoing pharmacological cardioversion (PCV) with flecainide.
      Parameters were computed on 10-s 12-lead ECGs of 221 patients before drug
      administration. The ability of ECG parameters to predict successful PCV and
      progression to persistent AF (mean follow-up 49 months) was evaluated and
      compared with common clinical predictors. Optimal prediction performance of
      successful PCV using only one ECG parameter was low, using dominant atrial
      frequency [lead II, receiver operating area under curve (AUC) 0.66, 95%
      confidence interval [0.64-0.67]], but the optimal combination of several ECG
      parameters strongly improved predictive performance (AUC 0.78 [0.76-0.79]). While
      predictive value of the optimal combination of clinical predictors was low (AUC
      0.68 [0.66-0.70], using right atrial volume and weight), adding ECG parameters
      strongly increased performance (AUC 0.81 [0.79-0.82], P < 0.001). Interestingly,
      higher dominant frequency and higher f-wave amplitude were associated with
      increased risk of progression to persistent AF during follow-up. Conclusion:
      Assessment of AF complexity from 12-lead ECGs significantly improves prediction
      of successful PCV and progression to persistent AF compared with common clinical
      and echocardiographic predictors.

PMID- 29016758
TI  - Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients
      undergoing elective cardioversion.
AB  - Aims: Non-vitamin K antagonist oral anticoagulants (NOAC) have been shown to be
      safe and effective alternatives to warfarin for the prevention of thromboembolic
      complications in patients with non-valvular atrial fibrillation (AF). The aim of
      this study was to investigate the complications and the use of NOACs in AF
      patients undergoing elective cardioversion. Methods and results: This nationwide
      multicentre study included consecutive elective cardioversions in AF patients
      treated with NOACs between October 2011 and May 2016. Data on patient
      characteristics, antithrombotic treatment and acute (<30 days) complications were
      collected. One thousand twenty-one patients (mean age 64 years, 70% men)
      underwent 1291 elective cardioversions, of which 680 (52.7%) cardioversions were
      performed in patients using dabigatran, 431 (33.4%) rivaroxaban, and 159 (12.3%)
      apixaban. Mean CHA2DS2-VASc score was 1.8 (+/-1.5). A total of 3 thromboembolic
      events occurred after the cardioversion (0.2%): 1 patient receiving dabigatran
      experienced an ischaemic stroke on Day 2 and 1 rivaroxaban treated patient on Day
      4. One patient receiving dabigatran experienced a transient ischaemic attack on
      Day 11. All 3 patients had used recommended doses of the NOAC. A total of 6
      (0.5%) clinically relevant, but not serious bleeding events occurred. Only short
      duration of AF was associated with lower rate of AF recurrence. Conclusion:
      Thrombotic and bleeding complications related to NOACs were uncommon (<0.5%) in
      real life AF patients undergoing elective cardioversion.

PMID- 29016754
TI  - Cardiac troponins: from myocardial infarction to chronic disease.
AB  - Elucidation of the physiologically distinct subunits of troponin in 1973 greatly
      facilitated our understanding of cardiac contraction. Although troponins are
      expressed in both skeletal and cardiac muscle, there are isoforms of troponin I/T
      expressed selectively in the heart. By exploiting cardiac-restricted epitopes
      within these proteins, one of the most successful diagnostic tests to date has
      been developed: cardiac troponin (cTn) assays. For the past decade, cTn has been
      regarded as the gold-standard marker for acute myocardial necrosis: the
      pathological hallmark of acute myocardial infarction (AMI). Whilst cTn is the
      cornerstone for ruling-out AMI in patients presenting with a suspected acute
      coronary syndrome (ACS), elevated cTn is frequently observed in those without
      clinical signs indicative of AMI, often reflecting myocardial injury of 'unknown
      origin'. cTn is commonly elevated in acute non-ACS conditions, as well as in
      chronic diseases. It is unclear why these elevations occur; yet they cannot be
      ignored as cTn levels in chronically unwell patients are directly correlated to
      prognosis. Paradoxically, improvements in assay sensitivity have meant more
      differential diagnoses have to be considered due to decreased specificity, since
      cTn is now more easily detected in these non-ACS conditions. It is important to
      be aware cTn is highly specific for myocardial injury, which could be
      attributable to a myriad of underlying causes, emphasizing the notion that cTn is
      an organ-specific, not disease-specific biomarker. Furthermore, the ability to
      detect increased cTn using high-sensitivity assays following extreme exercise is
      disconcerting. It has been suggested troponin release can occur without
      cardiomyocyte necrosis, contradicting conventional dogma, emphasizing a need to
      understand the mechanisms of such release. This review discusses basic troponin
      biology, the physiology behind its detection in serum, its use in the diagnosis
      of AMI, and some key concepts and experimental evidence as to why cTn can be
      elevated in chronic diseases.

PMID- 29016760
TI  - Response to the 'Letter to the Editor' from Madaffari et al. about 'Reappraisal
      and new observations on atrial tachycardia ablated from the non-coronary aortic
      sinus of Valsalva'.

PMID- 29016761
TI  - Pulmonary vein laceration during cryoballoon ablation for the treatment of atrial
      fibrillation.

PMID- 29016759
TI  - Access to magnetic resonance imaging of patients with magnetic resonance
      conditional pacemaker and implantable cardioverter-defibrillator systems: results
      from the Really ProMRI study.
AB  - Aims: The Really ProMRI study evaluates magnetic resonance imaging (MRI) access
      for patients with cardiac implantable electronic devices (CIEDs) as well as the
      performance of magnetic resonance (MR)-conditional leads when undergoing MRI.
      Methods and results: Patients either with an MR-conditional pacemaker or
      implantable defibrillator (ICD) system or with at least a component (device or
      one or more leads) from an MR-conditional system, were asked to fill in a
      questionnaire when they were referred to a MR scan. The rate of prescription,
      denial, or execution of MR examinations was evaluated in a 1-year follow-up
      visit. In total, 555 patients [median age (interquartile range) 72.2 (62.2-78.6);
      72% male] were enrolled, 49% (270) with a pacemaker, 51% (285) with an ICD
      system. Five-hundred and ten patients completed the follow-up period. A total of
      37 MRI referrals were reported in 35 patients, with a consequent event rate of
      7.0/100 patient-years (CI, 4.9-9.7). Fourteen were denied, while 23 [66%; (CI, 48
      81%)] were performed. The number of patients with MR referrals was not
      statistically different between pacemaker and ICD groups (21 vs. 14; P = 0.178).
      The rate of scans performed was higher in the pacemaker subjects (19/23 vs. 4/14,
      P = 0.003), while it was similar between patients with or without a complete MR
      conditional system (19/30 vs. 4/7, P = 0.606). Conclusion: In this study, we
      reported a 7.0/100 patient-year's event rate of MR prescriptions in CIED
      patients. Many examinations were denied, despite MR-conditional systems,
      especially in ICD patients. Regulatory and cultural changes are needed to allow
      wider access to MR imaging in CIED patients with MR-conditional systems.

PMID- 29016762
TI  - Diagnosis of tooth ankylosis using panoramic views, cone beam computed
      tomography, and histological data: a retrospective observational case series
      study.
AB  - Objectives: The aim of this study was to determine whether cone beam computed
      tomography is a reliable radiological method to diagnose tooth ankylosis.
      Materials and methods: A series of teeth clinically diagnosed as ankylosed were
      collected after extraction in a private practice from 2009 to 2015 and analyzed
      retrospectively. Inclusion criteria comprised permanent molars extracted due to
      failed tooth eruption in the absence of any visible mechanical obstruction,
      existing panoramic view (PV), and cone beam computed tomography (CBCT) and
      histological sections of sufficient quality. The CBCT scans and PVs were
      evaluated twice for signs of ankylosis by two independent observers using the
      following score: clear signs, possible signs, and no signs. The histological
      sections were evaluated and graded similarly to the radiographs by a specialist
      blinded to the radiographs and treatment. Results: Out of an initial group of 22
      patients, 9 subjects with 10 affected teeth were included for final evaluation.
      The age ranged from 8.3 to 17 years. No agreement was seen in comparing the PV
      scores to the histological sections. Fair to moderate agreement was seen in
      comparing the CBCT scores to the histological sections. All histologically
      confirmed ankylosis were detected in CBCT by both observers but some false
      positive results were found. Limitation: Only a small sample size was available
      as the disorder is rare. It is difficult to distinguish ankylosis from primary
      failure of eruption. Conclusion: CBCT images can be a useful adjunctive
      diagnostic tool to diagnose ankylosed teeth, but cannot be recommended as a
      single diagnostic modality as false positive results were found.

PMID- 29016763
TI  - A cephalometric study of the skeletal and dento-alveolar effects of the modified
      Louisiana State University activator in Class II malocclusion.
AB  - Objectives: To analyse the skeletal and dento-alveolar effects of the modified
      Louisiana State University activator (MLSUA) in Class II treatment. Materials and
      methods: A test group of 46 participants (25 females, 21 males) with Class II
      malocclusion treated with MLSUA followed by fixed appliances was compared with a
      matched Class II control group. Lateral cephalograms were taken at T1 (initial
      records), T2 (completion of MLSUA treatment), and T3 (before deband). The
      participants were also divided into two groups: pre-pubertal and pubertal
      according to skeletal maturity and three groups of different vertical facial
      patterns at the start of the treatment: brachyfacial, mesofacial, and
      dolichofacial. Statistical comparisons were performed with t-tests and analysis
      of variance (ANOVA). Results: Statistically significant supplementary mandibular
      growth (Co-Gn) in the test group (2.6 mm) was associated with improvement of
      overjet (OJ), overbite (OB), and molar relationship. Short-term mandibular growth
      was greater in pubertal than pre-pubertal groups (2.4 mm, P < 0.05). Mandibular
      incisors retroclined by 2.1 degrees after MLSUA treatment. The brachyfacial group
      showed greater reduction in the ANB angle and forward movement of pogonion.
      Mandibular, palatal, and occlusal plane angles showed insignificant change
      regardless of the facial type. Conclusions: MLSUA treatment corrected the Class
      II malocclusion by accelerating mandibular growth in the short-term with minimal
      dento-alveolar compensation, and the correction was maintained before deband. The
      treatment may be more effective if started at puberty. The mandibular, palatal,
      and occlusal planes remained stable throughout the treatment. Brachyfacial
      patients showed more favourable horizontal growth.

PMID- 29016764
TI  - Development of a novel shock wave catheter ablation system-A validation study in
      pigs in vivo.
AB  - Aims: Although the radiofrequency catheter ablation (RFCA) is widely used for the
      treatment of tachyarrhythmias, it has three fundamental weaknesses as a thermal
      ablation system, including a limited lesion depth, myoendocardial injury linking
      to thromboembolism, and prolonged inflammation followed by subsequent
      recurrences. In order to overcome these limitations, we have been developing a
      shock wave (SW) catheter ablation (SWCA) system as a novel non-thermal therapy.
      In the present study, we validated our new SWCA system with increased SW
      intensity. Methods and results: In a total of 36 pigs, we applied our new SWCA to
      ventricular muscle in vivo for the following protocols. (i) Epicardial approach
      (n = 17): The lesion depth achieved by the SWCA from the epicardium was examined.
      High intensity SW achieved 5.2 +/- 0.9 mm lesions (35 applications), where there
      was a strong correlation between SW intensity and lesion depth (R = 0.80, P <
      0.001, 54 applications). (ii) Endocardial approach (n = 6): The extent of
      endocardial injury with the two energy sources was examined by electron
      microscopy (8 applications each). Shock wave catheter ablation markedly reduced
      myoendothelial injury compared with RFCA (4.3 +/- 1.2 vs. 79.6 +/- 4.8%, P <
      0.01). The electrophysiological effects on the SW lesions were also confirmed
      using three-dimensional mapping system. (iii) Time-course study (n = 6 each): The
      healing process after ablation therapy was examined. We found transient
      inflammatory responses and accelerated reparative process with preserved blood
      flow in the SWCA group. Conclusion: These results indicate that our SWCA system
      is characterized, as compared with RFCA, by deeper lesion depth, markedly less
      myoendocardial injury and accelerated tissue repair process.

PMID- 29016765
TI  - Broad antiarrhythmic effect of mexiletine in different arrhythmia models.
AB  - Aims: Experimental studies and clinical reports suggest antiarrhythmic properties
      of mexiletine in different arrhythmias. We aimed at investigating mexiletine in
      experimental models of atrial fibrillation (AF) as well as in long-QT- (LQTS) and
      short-QT-syndrome (SQTS). Methods and results: In 15 isolated rabbit hearts,
      erythromycin (300 uM) was infused for simulation of long-QT-2-syndrome. In
      further 13 hearts, veratridine was administered to simulate long-QT-3-syndrome.
      Both drugs induced a significant QT-prolongation (erythromycin: +87 ms, P < 0.01;
      veratridine: +19 ms, P < 0.05) and increased dispersion of repolarization
      (erythromycin: +55 ms, P < 0.01; veratridine +31 ms, P < 0.01). Additional
      infusion of mexiletine (25 uM) resulted in a significant reduction of dispersion
      (erythromycin: -43 ms, P < 0.01; veratridine: -26 ms, P < 0.05). Reproducible
      induction of torsade de pointes was observed in 13 of 15 erythromycin-treated
      hearts (192 episodes) and 6 of 13 veratridine-treated hearts (36 episodes).
      Additional infusion of mexiletine significantly reduced ventricular tachycardia
      (VT) incidence. With mexiletine, only 3 of 15 erythromycin-treated hearts (27
      episodes) and 1 of 13 veratridine-treated hearts (2 episodes) presented
      polymorphic VT. In additional 9 hearts, the IK-ATP-channel-opener pinacidil was
      employed to simulate SQTS and significantly abbreviated ventricular
      repolarization (QT-interval: -18 ms, P < 0.05) and enhanced induction of
      ventricular fibrillation (VF). Mexiletine reversed the effects of pinacidil,
      increase refractory period (+127 ms, P < 0.01) and significantly suppressed
      induction of VF. In further 13 hearts AF was induced by combined treatment with
      acetylcholine/isoproterenol. Mexiletine also increased atrial refractory period
      (+80 ms, P < 0.01) and thereby effectively suppressed atrial fibrillation.
      Conclusion: Acute infusion of mexiletine significantly reduced the occurrence of
      polymorphic VT in the presence of pharmacologically simulated LQTS. Furthermore,
      mexiletine demonstrated potent antiarrhythmic properties in a model of SQTS and
      in AF.

PMID- 29016766
TI  - Temporal pattern/episode duration-based classification of atrial fibrillation as
      paroxysmal vs. persistent: is it time to develop a more integrated prognostic
      score to optimize management?
AB  - Atrial fibrillation (AF) is a clinically heterogeneous arrhythmia that is
      currently classified according to the variety of temporal rhythm based
      manifestations observed clinically, including 'first detected episode',
      'paroxysmal', 'persistent', or 'permanent' AF. Despite being widely adopted by
      the most recent consensus guidelines, the utility of this classification system
      to stratify patients into distinct and clinically useful groups that have
      different outcomes including mortality, morbidity, specific cardiovascular
      outcomes, and quality of life (QoL), remains questionable. This is particularly
      true regarding the distinction between paroxysmal and persistent AF. Here, we
      demonstrate there is limited and conflicting evidence that this distinction is
      useful in predicting mortality, morbidity (including stroke and heart failure),
      symptom burden and QoL, although there is convincing evidence that patients with
      paroxysmal AF have favourable outcomes following electrical cardioversion and
      have better ablation procedural outcomes. Risk stratification schemes including
      the CHA2DS2VASc score are widely used to help clinicians stratify patients at
      high risk of stroke, whilst a number of newer, potentially superior, competitors
      have also recently been developed. A range of parameters including left atrial
      (LA) size, LA morphology, LA fibrosis [assessed by magnetic resonance imaging
      (MRI)] LA appendage morphology and LA function (assessed by echo) have all been
      recently suggested to identify higher risk patients and may, perhaps in
      combination with validated risk stratification scores and emerging genetic data,
      provide clinicians with the information necessary to more accurately stratify
      patients to ensure better outcomes of specific AF treatments and prevent adverse
      events.

PMID- 29016767
TI  - Dual-loop circuit of ventricular tachycardia in repaired tetralogy of Fallot
      patient.

PMID- 29016768
TI  - Pulmonary vein re-mapping after cryoballoon ablation for atrial fibrillation.
AB  - Aims: Establishment of pulmonary vein isolation (PVI) during cryoballoon (CB)
      ablation is generally confirmed by use of an octapolar inner-lumen mapping
      catheter (Achieve(r)). The aim of this study is to evaluate the residual PV
      potential (PVP) using the conventional circular catheter after CB-PVI. Methods
      and results: A total of 105 consecutive patients (418 PVs) with paroxysmal AF who
      underwent the initial CB-PVI were prospectively included in this study. Of those,
      305 (73%) PVs with real-time recordings of PVP elimination by Achieve(r) catheter
      during successful PVI were included. After isolation of all 4 PVs, PV antral
      remapping by conventional circular mapping catheter was performed. After CB-PVI,
      residual PVP was detected in 4.3% (13/305) of PVs (1.2% of left-superior PV, 2.5%
      of left-inferior PV, none of right-superior PV, and 20% of right-inferior PV).
      Almost 60% of residual PV potential was located around the bottom portion of the
      right-inferior PV. In PVs with residual potential, PV trunk was shorter (12.7 +/-
      5.7 mm vs. 18.7 +/- 7.9, P = 0.001), minimal balloon temperature was higher (
      46.6 +/- 5.9  degrees C vs. -50.9 +/- 8.2, P = 0.02), and balloon warming time
      was shorter (35.6 +/- 17.8 s vs. 50.0 +/- 22.8, P = 0.006) than those without.
      All residual potentials were eliminated by additional touch up ablation. After
      the initial ablation procedure, 1-year AF-free rate was 79.5%. Conclusion: PV
      remapping after CB-PVI revealed residual antral PVP in 4.3% of PVs and in 20% of
      RIPVs in particular. The Achieve(r) catheter sometimes fails to detect complete
      PV antral isolation.

PMID- 29016769
TI  - Safety and efficiency of porous-tip contact-force catheter for drug-refractory
      symptomatic paroxysmal atrial fibrillation ablation: results from the SMART SF
      trial.
AB  - Aims: THERMOCOOL SMARTTOUCH(r) SF Catheter is a new contact-force (CF)-sensing
      catheter with 56-hole porous tip designed for improved cooling and reduced fluid
      delivery compared with a standard 6-hole open-irrigated catheter. The SMART SF
      study examined the periprocedural safety, acute effectiveness, and procedural
      efficiency of the catheter for drug-refractory symptomatic paroxysmal atrial
      fibrillation (PAF) ablation. Methods and results: The prospective, open-label,
      non-randomized SMART-SF was conducted at 17 US sites. Circumferential pulmonary
      vein (PV) isolation was performed with confirmation of entrance block in all PVs.
      Stable ablation sites were identified using CARTO VISITAGTM Module. Primary
      adverse events (AEs; <=1 week of index procedure), periprocedural AEs within 30
      days of ablation procedure, acute effectiveness (confirmation of entrance block
      for targeted PVs), CF, and procedural parameters were assessed. Overall, 165
      patients were enrolled (mean age, 62.7 years; male, 57.9%; white, 97%; left
      ventricular ejection fraction, 60.1 +/- 7%; left atrium diameter, 38.8 +/- 6 mm);
      159 underwent radiofrequency ablation and comprised the safety cohort. Primary
      safety performance criteria were met: primary AE rate was 2.5% (4/159; cardiac
      tamponade [n = 2], thrombo-embolism [n = 1], transient ischaemic attack [n = 1]).
      All primary AEs resolved/improved within the 1-month follow-up period. Acute
      procedural effectiveness was attained in 96.2% (95% confidence interval: 92.0
      98.6%) of patients. Procedure time, fluoroscopy time, and fluid delivered were
      observed in comparison to predecessor catheters. Conclusion: In the SMART-SF
      trial, the predetermined safety performance goal was met, demonstrating the
      safety and acute effectiveness of the THERMOCOOL SMARTTOUCH(r) SF Catheter for
      PAF ablation.

PMID- 29016770
TI  - Development and validation of a risk score for predicting atrial fibrillation
      recurrence after a first catheter ablation procedure - ATLAS score.
AB  - Aims: Several predictors of relapse after catheter ablation of atrial
      fibrillation (AF) have been established, but assessing each patient's individual
      risk remains challenging. Our aim was to develop and validate a score to estimate
      the risk of AF recurrence after the first radiofrequency pulmonary vein isolation
      (PVI) procedure. Methods and results: Independent predictors of AF relapse were
      identified retrospectively in a two-centre registry of 1934 patients who
      underwent a first PVI procedure. Using the Cox regression hazard ratios of
      designated variables, a risk score was developed in a random sample of 50% of the
      patients (development cohort) and validated in the remaining (validation cohort)
      half. The accuracy and discriminative power of the predictive model were assessed
      in both subgroups. During a follow-up of 4.2 +/- 2.7 years, 522 patients (27%)
      relapsed. Five independent predictors of AF recurrence were identified and
      included in the score: age >60 years (1 point), female sex (4 points), non
      paroxysmal AF (2 points), current smoking (7 points) and indexed left atrial
      volume (1 point for each 10 mL/m2). The score showed good discriminative power
      (censored c-statistic of 0.75 in both cohorts). In the development group, AF
      relapse rates were 8, 11, and 17%/year for low (<6 points), intermediate (6-10
      points), and high-risk patients (>10 points), respectively (P < 0.001). In the
      validation group, AF recurrence rates were 8, 11, and 18%/year, respectively (P <
      0.001). Conclusion: A simple risk score to estimate the rate of AF recurrence
      after ablation was developed and validated. An external assessment of its
      usefulness as a patient selection tool seems warranted.

PMID- 29016771
TI  - Predictors of long-term survival free from relapses after extraction of infected
      CIED.
AB  - Aims: We explored the possible predictors of long-term prognosis after
      transvenous lead extraction (TLE) for a cardiac implantable device related
      infection (CIEDI), including the modified Duke score result. Methods and results:
      We performed a single centre prospective observational study in a population of
      consecutive patients referred for TLE to a teaching hospital to treat a CIEDI
      without associated valve-endocarditis. 121 patients were enrolled between January
      2012 and March 2016. According to the modified Duke criteria, the presence of
      CIED-related endocarditis was rejected in 54.5%, possible in 21.5%, and definite
      in 24.0%. 20/121 patients died after a mean follow-up of 46.0 +/- 2.5 months,
      while 7 patients reported hospitalization for CIEDI recurrence/relapse in the
      same period. Modified Duke score was significantly associated with a poor
      prognosis at univariate Cox regression analysis (HR 1.847, 95% CI 1.160-2.941; P
      = 0.010). However, the three factors independently associated with death and/or
      CIEDI relapse/recurrence were: a 'closed' CIED pocket (HR 2.720; 95% CI 1.135
      6.520), presence of ghost at post-TLE transoesophageal echocardiography (HR
      3.469; 95% CI 1.420-8.878), and a GFR <60 (HR 4.565; 95% CI 1.668-12.493).
      Conclusion: CIEDI has a poor long-term prognosis despite an effective TLE. Renal
      failure, presence of 'ghosts' at post-TLE transoesophageal echocardiography and a
      closed CIED pocket are associated with a worse prognosis.

PMID- 29016772
TI  - Do women benefit equally as men from the primary prevention implantable
      cardioverter-defibrillator?
AB  - Women traditionally have been and are still underrepresented in research in many
      important areas of cardiology, and guideline recommendations which also encompass
      women are mostly based on research conducted predominantly in men. However, there
      is plausible cause to believe that sex may have a potential influence on the
      benefit derived from the implantable cardioverter-defibrillators (ICD), alone or
      in association with cardiac resynchronization therapy. We assessed the possible
      relationship between sex and outcome with ICD implantation in the setting of
      primary prevention, by pooling the results of MUSTT, MADIT-II, DEFINITE,
      COMPANION, SCD-HeFT and DANISH trials in a meta-analysis. We pooled results for
      female and male patients separately. The results suggest that women as a group do
      not seem to obtain a significant survival benefit from the primary prevention
      ICD, contrary to men. This in turn may also have contributed to a relative
      underestimation of the ICD benefit among males when looking at the results in
      total. It is time for the medical and research communities to actively question
      the presumed overarching benefit of ICDs irrespective of sex and engage in
      systematic scientific efforts to definitively evaluate the value of this
      intervention in women.

PMID- 29016773
TI  - Multichannel electrocardiogram diagnostics for the diagnosis of arrhythmogenic
      right ventricular dysplasia.
AB  - Aims: The identification of arrhythmogenic right ventricular dysplasia (ARVD)
      from 12-channel standard electrocardiogram (ECG) is challenging. High density ECG
      data may identify lead locations and criteria with a higher sensitivity. Methods
      and results: Eighty-channel ECG recording from patients diagnosed with ARVD and
      controls were quantified by magnitude and integral measures of QRS and T waves
      and by a measure (the average silhouette width) of differences in the shapes of
      the normalized ECG cycles. The channels with the best separability between ARVD
      patients and controls were near the right ventricular wall, at the third
      intercostal space. These channels showed pronounced differences in P waves
      compared to controls as well as the expected differences in QRS and T waves.
      Conclusion: Multichannel recordings, as in body surface mapping, add little to
      the reliability of diagnosing ARVD from ECGs. However, repositioning ECG
      electrodes to a high anterior position can improve the identification of ECG
      variations in ARVD. Additionally, increased P wave amplitude appears to be
      associated with ARVD.

PMID- 29016774
TI  - Alveolar bone changes after rapid maxillary expansion with tooth-born appliances:
      a systematic review.
AB  - Background: During rapid maxillary expansion (RME), heavy forces are transmitted
      to the maxilla by the anchored teeth causing buccal inclination and buccal bone
      loss of posterior teeth. Objective: To systematically review the literature in
      order to investigate whether RME causes periodontal sequelae, assessed by cone
      beam computed tomography (CBCT). Search methods: Fifteen electronic databases and
      reference lists of studies were searched up to March 2017. Selection criteria: To
      be included in the systematic review, articles must be human studies on growing
      subjects, with transversal maxillary deficiency treated with RME and with
      assessment of buccal bone loss by CBCT images. Only randomized and non-randomized
      trials were included. Data collection and analysis: Two authors independently
      performed study selection, data extraction, and risk of bias assessment. Study
      characteristics (study design, sample size, age, sex, skeletal maturity, type of
      appliance, daily activation, evaluated linear measurements, observation period,
      CBCT settings), and study outcomes (loss of buccal bone thickness and marginal
      bone) were reported according to the PRISMA statement. Results: On the basis of
      the applied inclusion criteria, only six articles, three randomized clinical
      trials and three controlled clinical trials were included. An individual analysis
      of the selected articles was undertaken. The risks of bias of the six trials were
      scored as medium to low. Limitations: The results of the present systematic
      review are based on a limited number of studies and only one study included a
      control group. Conclusions and implications: In all considered studies,
      significant loss of buccal bone thickness and marginal bone level were observed
      in anchored teeth, following RME. Further prospective studies correlating the
      radiological data of bone loss to the periodontal soft tissues reaction after RME
      are required. A preliminary evaluation of the patient-related risk factors for RR
      may be advisable when considering to administering RME. Registration: This
      systematic review was registered in the National Institute of Health Research
      database with an appropriate protocol number (http://www.crd.york.ac.uk/PROSPERO
      Protocol: CRD42017062645). Funding: The present study has not received any
      contributions from private or public funding agencies.

PMID- 29016775
TI  - Emerging molecular therapies targeting myocardial infarction-related arrhythmias:
      the role of miRNAs regulation.

PMID- 29016776
TI  - Atrial fibrillation is associated with decreased total cerebral blood flow and
      brain perfusion.
AB  - Aims: Atrial fibrillation (AF) has been associated with cognitive impairment.
      Additionally, brain volume may be reduced in individuals with AF. Potential
      causes may include cerebral micro-embolism or reduced stroke volume due to the
      beat-to-beat variation in AF. The aims of this study were to measure cerebral
      blood flow and estimate whole brain perfusion in elderly individuals with and
      without AF. Methods and results: Blood flow in the cervical arteries was measured
      with phase contrast MRI and brain perfusion estimated in a large cohort from the
      AGES-Reykjavik Study. Individuals were divided into three groups at the time of
      the MRI: persistent AF, paroxysmal AF, and no history of AF. Of 2291 participants
      (mean age 79.5 years), 117 had persistent AF and 78 had paroxysmal AF but were in
      sinus rhythm at the time of imaging AF. Those with persistent AF had lower
      cholesterol and used more anti-hypertensive medication and warfarin. The three
      groups were similar with regard to other cardiovascular risk factors. Those in
      the persistent AF group had significantly lower total cerebral blood flow on
      average, 472.1 mL/min, both when compared with the paroxysmal AF group, 512.3
      mL/min (P < 0.05) and the no AF group, 541.0 mL/min (P < 0.001). Brain perfusion
      was lowest in the persistent AF group, 46.4 mL/100 g/min compared with the
      paroxysmal AF group, 50.9 mL/100 g/min in (P < 0.05) and those with no AF, 52.8
      mL/100 g/min (P < 0.001). Conclusion: Persistent AF decreases blood flow to the
      brain as well as perfusion of brain tissue compared with sinus rhythm.

PMID- 29016777
TI  - Long-term impact of intrathoracic impedance findings on survival and heart
      failure hospitalizations after cardiac resynchronization therapy in ICD Registry
      patients.
AB  - Aims: To determine adjusted associations among OptiVol(r) threshold crossings,
      long-term survival, and hospitalizations among heart failure (HF) patients with
      Medicare coverage in the United States. Methods and results: A cohort with
      OptiVol(r)-enabled cardiac resynchronization therapy defibrillators (CRT-D)
      devices from the Implantable Cardioverter Defibrillator Registry was linked to
      both Medicare claims/summary data and Medtronic's CareLink(r) Network data. An
      extended multivariable Cox model was used to analyse associations among
      OptiVol(r) threshold crossings (treated as time-dependent covariates), mortality,
      and HF-related hospitalizations (HFH). We analysed N = 1565 patients with
      OptiVol(r)-enabled CRT-D devices (mean age 72.8, 28% women). The median follow-up
      was 6.3 years. Patients with >15.1% of days above OptiVol(r) threshold (highest
      quartile) had more than a 4-fold increase in mortality [hazard ratio (HR) 4.2,
      95% confidence interval (CI): 3.3-5.3] and more than a 3-fold increase in HFH (HR
      3.2, 95% CI: 2.4-4.2) compared with patients having <4.1% of days above threshold
      (lowest quartile) after adjustment for key covariates. In addition, a single
      OptiVol(r) crossing was associated with significantly increased rates of both
      mortality (HR 1.87, 95% CI: 1.27-2.75) and HFH (HR 1.70, 95% CI: 1.28-2.27).
      Conclusion: In a CRT-D cohort with over 6 years of follow-up, both single
      OptiVol(r) crossings and time above OptiVol(r) threshold were associated with
      increased rates of mortality and hospitalization, which has important
      implications for clinical care. This is the first study integrating device data
      with Medicare outcomes to validate the long-term significance of OptiVol(r)
      findings.

PMID- 29016778
TI  - Comparison between endocardial and epicardial cardiac resynchronization in an
      experimental model of non-ischaemic cardiomyopathy.
AB  - Aims: Pacing from the left ventricular (LV) endocardium might increase the
      likelihood of response to cardiac resynchronization therapy. However,
      experimental and clinical data supporting this assumption are limited and
      controversial. The aim of this study was to compare the acute response of
      biventricular pacing from the LV epicardium and endocardium in a swine non
      ischaemic cardiomyopathy (NICM) model of dyssynchrony. Methods and results: A
      NICM was induced in six swine by 3 weeks of rapid ventricular pacing.
      Biventricular stimulation was performed from 16 paired locations in the LV (8
      epicardial and 8 endocardial) with two different atrioventricular (80 and 110 ms)
      intervals and three interventricular (0, +30, -30 ms) delays. The acute response
      of the aortic blood flow, LV and right ventricular (RV) pressures, LVdP/dtmax and
      LVdP/dtmin and QRS complex width and QT duration induced by biventricular
      stimulation were analysed. The haemodynamic and electrical beneficial responses
      to either LV endocardial or epicardial biventricular pacing were similar
      (DeltaLVdP/dtmax: +7.8 +/- 2.2% ENDO vs. +7.3 +/- 1.5% EPI, and DeltaQRS width: 
      16.8 +/- 1.3% ENDO vs. -17.1 +/- 1.9% EPI; P = ns). Pacing from LV basal regions
      either from the epicardium or endocardium produced better haemodynamic responses
      as compared with mid or apical LV regions (P < 0.05). The LV regions producing
      the maximum QRS complex shortening did not correspond to those inducing the best
      haemodynamic responses (EPI: r2 = 0.013, P = ns; ENDO: r2 = 0.002, P = ns).
      Conclusion: Endocardial LV pacing induced similar haemodynamic changes than
      pacing from the epicardium. The response to endocardial LV pacing is region
      dependent as observed in epicardial pacing.

PMID- 29016779
TI  - Is less more? Impact of different ablation protocols on periprocedural
      complications in second-generation cryoballoon based pulmonary vein isolation.
AB  - Aims: Second-generation cryoballoon (CB2) based pulmonary vein isolation (PVI)
      has emerged as an effective treatment option for symptomatic atrial fibrillation
      (AF). The current study sought to assess the impact of different ablation
      protocols on the incidence and characteristics of procedural complications in a
      large patient cohort. Methods and results: A total of 563 consecutive patients
      with symptomatic AF who underwent CB2-based ablation between July 2012 and
      January 2016, were assessed. Three different ablation protocols were applied and
      characterized by (#1) a bonus-freeze following PVI, (#2) no bonus-freeze after
      PVI, and (#3) a 'time-to-effect'-guided strategy. Major complications occurred in
      30/563 patients (5.3%) with phrenic nerve palsy (PNP) as the most frequent
      complication occurring in 2.7% of the cases. The overall incidence of
      complications was significantly lower in patients treated with a 'time-to-effect'
      guided ablation strategy compared with the other ablation protocols (8.1%
      [17/211] (protocol #1+#2) vs. 3.7% [13/352] (protocol #3), respectively; P =
      0.026). The 'time-to-effect' guided ablation protocol was associated with less
      applied freeze-cycles and shorter freeze-cycle durations. Additionally, shorter
      procedure times, radiation exposures and lower volumes of contrast medium needed
      were assessed for the 'time-to-effect' guided protocol as compared with the other
      ablation protocols. Conclusion: The overall incidence of complications was 5.3%
      in our analysis. The most frequent complication was PNP. The use of a time-to
      effect guided ablation protocol was associated with a lower incidence of major
      complications compared with a bonus-freeze and no bonus-freeze protocol.

PMID- 29016780
TI  - Analysis of the heart rate variability during cryoballoon ablation of atrial
      fibrillation.
AB  - Aims: Vagal responses such as marked bradycardia or a rapid blood pressure
      decrease are often observed during pulmonary vein (PV) isolation of atrial
      fibrillation (AF) using a cryoballoon (CB). However, the relationship between the
      marked vagal response and change in the heart rate variability (HRV) as a marker
      of the autonomic tone is not well understood. Methods and results: Fifty-four
      paroxysmal AF patients underwent CB ablation. The CB ablation was started from
      the right sided PVs in 25 patients (R group) and left sided PVs in 29 (L group).
      The HRV and haemodynamic status during the procedure were analysed. A vagal
      response was observed in 16 L group patients (61.5%) during the ablation of the
      different PVs (RSPV:1, RIPV:5, LSPV:15, LIPV:5), while it was observed in only 2
      R group patients (9.5%) (RSPV:0, RIPV:0, LSPV:1, LIPV:1) (P = 0.0002). The HRV in
      the L group was significantly higher than that in the R group just after the CB
      ablation especially for the left sided PVs (L group vs. R group, total power of
      the HRV, median; RSPV, 11184.7 vs. 4360.0, P = 0.21; RIPV, 9044.3 vs. 2115.1, P =
      0.01; LSPV, 21186.0 vs. 1314.2, P = 0.0002; LIPV 10265.9 vs. 1236.2, P = 0.0007).
      Conclusion: A marked increase in the HRV parameters was observed just after the
      CB ablation. An initial CB ablation of the right PVs decreased the change in the
      autonomic tone during the right PV ablation and subsequent left PV ablation. It
      prevented an excessive vagal response during the CB ablation and might be a safe
      procedure.

PMID- 29016781
TI  - Effectiveness, safety, and long-term outcomes of non-powered mechanical sheaths
      for transvenous lead extraction.
AB  - Aims: To analyse the effectiveness, safety and long-term outcomes of conventional
      non-powered mechanical systems for transvenous lead extraction (TLE) performed by
      experienced first operators. Outcomes were assessed according to lead location
      and type of operating room in which the procedure was performed. Methods and
      results: Data from 2049 patients (mean age: 65 years), with infectious (40%) or
      non-infectious (60%) indications, were analysed over a mean of 3.37 (+/-2.29)
      years. A total of 3426 leads were extracted; and, overall, 95% full procedural,
      4% partial procedural, and 98% clinical success were demonstrated. Within the
      patient cohort, 1.8% (37/2049) experienced major complications, with cardiac
      tamponade being predominant (30/37). Cardiac tamponade was identified as the main
      cause of mortality, as well as the cause of all procedure-related deaths (6/2049;
      0.3%). Cardiac tamponade occurred in 1.8% of atrial and 0.3% of right ventricular
      lead extractions, with fatal tamponade reported in 9% of atrial, 40% of
      ventricular, and 67% of coronary sinus lead extractions. No association between
      lead location and cardiac tamponade-related mortality was observed; however, lead
      location did affect the success of pericardiocentesis. The cardiac tamponade
      related mortality rate was 37% when TLE was performed in an electrophysiology
      laboratory. No deaths were reported when the procedure was performed in a cardiac
      surgery or hybrid operating room. Long-term survival was improved when TLE was
      performed due to non-infectious indications, rather than pocket infection or lead
      related endocarditis (P < 0.001). Conclusion: Using conventional non-powered
      mechanical sheaths, TLE was effective even in patients at high risk of
      complications.

PMID- 29016782
TI  - To downgrade, or not to downgrade: that is the question.

PMID- 29016783
TI  - High circulating adiponectin level is associated with poor clinical outcome after
      catheter ablation for paroxysmal atrial fibrillation.
AB  - Aims: Circulating adiponectin is known to have anti-diabetic, anti-atherogenic,
      and anti-inflammatory properties. However, the predictive value of adiponectin in
      cardiovascular disease has been reported to be contradictory ('adiponectin
      paradox') and its relationship with atrial fibrillation (AF) is controversial. We
      hypothesized that pre-procedural plasma level of adiponectin would have
      prognostic value in patients who underwent AF catheter ablation. Methods and
      results: This observational cohort study included 874 patients with paroxysmal AF
      (PAF) (73.0% male, mean age 57.6 +/- 11.2 years) who underwent catheter ablation.
      Quartile analyses of plasma level of adiponectin were performed to determine AF
      related clinical factors. Patients in the highest quartile of plasma adiponectin
      were more likely to be older (P < 0.001), female (P < 0.001), and have a higher
      CHA2DS2-VASc score (P < 0.001) than patients in the other three quartiles. Plasma
      level of adiponectin was independently associated with female gender (B 2.92
      [1.84~4.00], P < 0.001), older age (B 0.06 [0.03~0.10], P < 0.001), lower body
      mass index (B - 0.22 [-0.42~-0.03], P = 0.025), and greater LA volume index (B
      0.05 [0.01~0.08], P = 0.005). During the 29.9 +/- 18.0 months of follow-up,
      plasma adiponectin level (HR 1.17 [1.02~1.35], P = 0.022) was independently
      associated with clinical recurrence of AF, and the clinical recurrence rate was
      significantly higher in the highest quartile of adiponectin group than the others
      (log rank P = 0.029), especially in age <65 years (log rank P = 0.038), but not
      in age >=65. Conclusion: High circulating adiponectin is independently associated
      with AF recurrence after catheter ablation for PAF, especially younger than 65
      years old.

PMID- 29016785
TI  - Obstructive sleep apnea is associated with increased rotor burden in patients
      undergoing focal impulse and rotor modification guided atrial fibrillation
      ablation.
AB  - Aims: To assess whether obstructive sleep apnea (OSA) was associated with
      increased rotor burden among atrial fibrillation (AF) patients. Methods and
      results: We studied 33 consecutive patients who were scheduled for focal impulse
      and rotor modulation (FIRM) ablation at our institution to describe the mapping,
      ablation, and outcomes, among patients with and without OSA. Patients underwent
      biatrial FIRM mapping in AF with ablation of stable rotors in addition to
      conventional ablation lesion sets. Differences between groups were tested with
      student's t-tests and Fisher's exact tests, as appropriate. Survival analyses
      were performed using the Kaplan-Meier method. Twelve of the 33 (36%) patients had
      OSA and 8 (66%) used continuous positive airway pressure ventilation (CPAP).
      Obstructive sleep apnea patients had a higher body mass index (BMI) (33.6 vs.
      28.8 kg/m2, P = 0.01) and were more commonly on beta blockers (67% vs. 29%, P =
      0.03) but were otherwise similar regarding baseline characteristics, medication
      use, and prior AF treatments, including antiarrhythmic drugs and prior ablation.
      Focal impulse and rotor modulation mapping demonstrated increased rotor burden in
      the OSA patients (2.6 +/- 0.9 vs. 2.0 +/- 1.0, P =0.03). The increased rotor
      burden was more evident in the right atrium (RA) (1.0 +/- 0.7 vs. 0.5 +/- 0.7, P
      =0.04 compared with left atrium (1.7 +/- 0.8 vs. 1.4 +/- 0.7, P = 0.15). There
      was no correlation between BMI and total number of rotors (r = 0.0961, P = 0.59).
      Among the population of patients with OSA, CPAP therapy was associated with a
      lower number of RA rotors (0.8 +/- 0.7 vs. 1.5 +/- 0.6, P = 0.05) but no
      significant difference in overall rotors (P = 0.33). Conclusion: Obstructive
      sleep apnea patients demonstrate increased rotor prevalence, driven predominantly
      by an increase in RA rotors. CPAP therapy was associated with fewer RA rotors.

PMID- 29016784
TI  - Sex differences in outcomes of primary prevention implantable cardioverter
      defibrillator therapy: combined registry data from eleven European countries.
AB  - Aims: Therapy with an implantable cardioverter defibrillator (ICD) is established
      for the prevention of sudden cardiac death (SCD) in high risk patients. We aimed
      to determine the effectiveness of primary prevention ICD therapy by analysing
      registry data from 14 centres in 11 European countries compiled between 2002 and
      2014, with emphasis on outcomes in women who have been underrepresented in all
      trials. Methods and results: Retrospective data of 14 local registries of primary
      prevention ICD implantations between 2002 and 2014 were compiled in a central
      database. Predefined primary outcome measures were overall mortality and first
      appropriate and first inappropriate shocks. A multivariable model enforcing a
      common hazard ratio for sex category across the centres, but allowing for centre
      specific baseline hazards and centre specific effects of other covariates, was
      adjusted for age, the presence of ischaemic cardiomyopathy or a CRT-D, and left
      ventricular ejection fraction <=25%. Of the 5033 patients, 957 (19%) were women.
      During a median follow-up of 33 months (IQR 16-55 months) 129 women (13%) and 807
      men (20%) died (HR 0.65; 95% CI: [0.53, 0.79], P-value < 0.0001). An appropriate
      ICD shock occurred in 66 women (8%) and 514 men (14%; HR 0.61; 95% CI: 0.47-0.79;
      P = 0.0002). Conclusion: Our retrospective analysis of 14 local registries in 11
      European countries demonstrates that fewer women than men undergo ICD
      implantation for primary prevention. After multivariate adjustment, women have a
      significantly lower mortality and receive fewer appropriate ICD shocks.

PMID- 29016786
TI  - Sustainability of outdoor school ground smoking bans at secondary schools: a
      mixed-method study.
AB  - Background: Although increasing numbers of countries are implementing outdoor
      school ground smoking bans at secondary schools, less attention is paid to the
      post-implementation period even though sustainability of a policy is essential
      for long-term effectiveness. Therefore, this study assesses the level of
      sustainability and examines perceived barriers/facilitators related to the
      sustainability of an outdoor school ground smoking ban at secondary schools.
      Methods: A mixed-method design was used with a sequential explanatory approach.
      In phase I, 438 online surveys were conducted and in phase II, 15 semi-structured
      interviews were obtained from directors of relevant schools. ANOVA (phase I) and
      a thematic approach (phase II) were used to analyze data. Results: Level of
      sustainability of an outdoor school ground smoking ban was high at the 48% Dutch
      schools with an outdoor smoking ban. Furthermore, school size was significantly
      associated with sustainability. The perceived barriers/facilitators fell into
      three categories: (i) smoking ban implementation factors (side-effects,
      enforcement, communication, guidelines and collaboration), (ii) school factors
      (physical environment, school culture, education type and school policy) and
      (iii) community environment factors (legislation and social environment).
      Conclusions: Internationally, the spread of outdoor school ground smoking bans
      could be further promoted. Once implemented, the ban has become 'normal' practice
      and investments tend to endure. Moreover, involvement of all staff is important
      for sustainability as they function as role models, have an interrelationship
      with students, and share responsibility for enforcement. These findings are
      promising for the sustainability of future tobacco control initiatives to further
      protect against the morbidity/mortality associated with smoking.

PMID- 29016787
TI  - First-in-human: leadless Micra transcatheter pacing system meets the Nanostim
      leadless cardiac pacing system.

PMID- 29016788
TI  - Isolation of the superior vena cava from the right atrial posterior wall: a novel
      ablation approach.
AB  - Aims: Superior vena cava (SVC) isolation might be difficult to achieve because of
      the vicinity of the phrenic nerve (PN) and sinus node. Based on its
      embryogenesis, we hypothesized the presence of preferential conduction from the
      right atrial (RA) posterior wall, making it possible to isolate the SVC antrally,
      sparing its anterior and lateral aspect. Methods and results: This is a
      descriptive cohort study of 105 consecutive patients in which SVC isolation was
      obtained with radiofrequency ablation, starting in the septal aspect of the SVC
      RA junction and continued posteriorly and inferiorly targeting sites of early
      activation until electrical isolation was obtained. Acute SVC isolation was
      achieved in 103 (98%) patients; the mean distance between the site of SVC
      isolation and the SVC-RA junction was 19.9 +/- 5.3 (range 9.7-33.7) mm. During
      follow-up, 2 (2%) patients developed symptomatic diaphragmatic paralysis due to
      transient right PN injury; 13 patients underwent a repeat ablation: SVC
      reconnection was observed in 5 patients, and re-isolation was easily achieved by
      targeting the corresponding sites of early activation. Conclusion : Superior vena
      cava isolation can be completed by targeting its septal segment and sites of
      early activation in the posterior SVC-RA junction and RA posterior wall; this is
      a feasible alternative ablation strategy in patients in which SVC isolation
      cannot be completed with the standard approach. The risk of sinus node injury or
      SVC stenosis are eliminated; PN injury is still possible but can easily be
      prevented with high-output pacing to exclude a true posterior course of the PN.

PMID- 29016790
TI  - Upgrading or downgrading a cardiac resynchronization therapy device (CRT) device?
      Gaps and dilemmas in current clinical practice.

PMID- 29016789
TI  - A technology-based patient and family engagement consult service for the
      pediatric hospital setting.
AB  - Objective: The Vanderbilt Children's Hospital launched an innovative Technology
      Based Patient and Family Engagement Consult Service in 2014. This paper describes
      our initial experience with this service, characterizes health-related needs of
      families of hospitalized children, and details the technologies recommended to
      promote engagement and meet needs. Materials and Methods: We retrospectively
      reviewed consult service documentation for patient characteristics, health
      related needs, and consultation team recommendations. Needs were categorized
      using a consumer health needs taxonomy. Recommendations were classified by
      technology type. Results: Twenty-two consultations were conducted with families
      of patients ranging in age from newborn to 15 years, most with new diagnoses or
      chronic illnesses. The consultation team identified 99 health-related needs (4.5
      per consultation) and made 166 recommendations (7.5 per consultation, 1.7 per
      need). Need categories included 38 informational needs, 26 medical needs, 23
      logistical needs, and 12 social needs. The most common recommendations were
      websites (50, 30%) and mobile applications (30, 18%). The most frequent
      recommendations by need category were websites for informational needs (39, 50%),
      mobile applications for medical needs (15, 40%), patient portals for logistical
      needs (12, 44%), and disease-specific support groups for social needs (19, 56%).
      Discussion: Families of hospitalized pediatric patients have a variety of health
      related needs, many of which could be addressed by technology recommendations
      from an engagement consult service. Conclusion: This service is the first of its
      kind, offering a potentially generalizable and scalable approach to assessing
      health-related needs, meeting them with technologies, and promoting patient and
      family engagement in the inpatient setting.

PMID- 29016791
TI  - Socioeconomic status and infectious intestinal disease in the community: a
      longitudinal study (IID2 study).
AB  - Background: Infectious intestinal diseases (IID) are common, affecting around 25%
      of people in UK each year at an estimated annual cost to the economy, individuals
      and the NHS of L1.5 billion. While there is evidence of higher IID hospital
      admissions in more disadvantaged groups, the association between socioeconomic
      status (SES) and risk of IID remains unclear. This study aims to investigate the
      relationship between SES and IID in a large community cohort. Methods:
      Longitudinal analysis of a prospective community cohort in the UK following 6836
      participants of all ages was undertaken. Hazard ratios for IID by SES were
      estimated using Cox proportional hazard, adjusting for follow-up time and
      potential confounding factors. Results: In the fully adjusted analysis, hazard
      ratio of IID was significantly lower among routine/manual occupations compared
      with managerial/professional occupations (HR 0.74, 95% CI 0.61-0.90). Conclusion:
      In this large community cohort, lower SES was associated with lower IID risk.
      This may be partially explained by the low response rate which varied by SES.
      However, it may be related to differences in exposure or recognition of IID
      symptoms by SES. Higher hospital admissions associated with lower SES observed in
      some studies could relate to more severe consequences, rather than increased
      infection risk.

PMID- 29016794
TI  - Epidemiology of chronic respiratory diseases and associated factors in the adult
      Italian population.
AB  - Background: Detailed epidemiology of Chronic Respiratory Diseases (CRDs) and of
      their risk and protective factors is needed to plan preventive interventions to
      reduce the burden of CRDs on population health. This study determines the
      prevalence of doctor-diagnosed CRDs and its associated factors in the adult
      Italian population. Methods: Data was collected from adults participating in the
      ongoing cross-sectional Italian Behavioural Risk Factor Surveillance System
      (PASSI) between 2013 and 2015. Results: Among 108 705 respondents, 7.0% reported
      a CRD (3.4% asthma, 2.6% COPD, 1.0% Asthma-COPD Overlap Syndrome). Current
      smoking was more frequent in the group with CRD compared to those without (30.8%
      vs. 25.2%, P < 0.001), as was physical inactivity (41.9% vs. 36.4%, P 0.009) and
      overweight/obesity (52.4% vs. 41.4%, P 0.009). Adults with CRDs also reported
      appropriate perception of insufficient physical activity and excessive body
      weight, adopted protective behaviours and received preventive interventions more
      often than those without CRDs. Conclusions: Italian adults with CRDs are more
      likely to be exposed to aggravating factors but are also knowledgeable of their
      condition and amenable to behaviour change. Since effective interventions for
      modifying these factors are available, there is an opportunity to reduce the
      significant disease burden of CRDs through specifically targeted health promotion
      interventions.

PMID- 29016793
TI  - Mining 100 million notes to find homelessness and adverse childhood experiences:
      2 case studies of rare and severe social determinants of health in electronic
      health records.
AB  - Objective: Understanding how to identify the social determinants of health from
      electronic health records (EHRs) could provide important insights to understand
      health or disease outcomes. We developed a methodology to capture 2 rare and
      severe social determinants of health, homelessness and adverse childhood
      experiences (ACEs), from a large EHR repository. Materials and Methods: We first
      constructed lexicons to capture homelessness and ACE phenotypic profiles. We
      employed word2vec and lexical associations to mine homelessness-related words.
      Next, using relevance feedback, we refined the 2 profiles with iterative searches
      over 100 million notes from the Vanderbilt EHR. Seven assessors manually reviewed
      the top-ranked results of 2544 patient visits relevant for homelessness and 1000
      patients relevant for ACE. Results: word2vec yielded better performance (area
      under the precision-recall curve [AUPRC] of 0.94) than lexical associations
      (AUPRC = 0.83) for extracting homelessness-related words. A comparative study of
      searches for the 2 phenotypes revealed a higher performance achieved for
      homelessness (AUPRC = 0.95) than ACE (AUPRC = 0.79). A temporal analysis of the
      homeless population showed that the majority experienced chronic homelessness.
      Most ACE patients suffered sexual (70%) and/or physical (50.6%) abuse, with the
      top-ranked abuser keywords being "father" (21.8%) and "mother" (15.4%). Top
      prevalent associated conditions for homeless patients were lack of housing
      (62.8%) and tobacco use disorder (61.5%), while for ACE patients it was mental
      disorders (36.6%-47.6%). Conclusion: We provide an efficient solution for mining
      homelessness and ACE information from EHRs, which can facilitate large clinical
      and genetic studies of these social determinants of health.

PMID- 29016792
TI  - Antidepressant-Like Actions of Inhibitors of Poly(ADP-Ribose) Polymerase in
      Rodent Models.
AB  - Background: Many patients suffering from depressive disorders are refractory to
      treatment with currently available antidepressant medications, while many more
      exhibit only a partial response. These factors drive research to discover new
      pharmacological approaches to treat depression. Numerous studies demonstrate
      evidence of inflammation and elevated oxidative stress in major depression.
      Recently, major depression has been shown to be associated with elevated levels
      of DNA oxidation in brain cells, accompanied by increased gene expression of the
      nuclear base excision repair enzyme, poly(ADP-ribose) polymerase-1. Given these
      findings and evidence that drugs that inhibit poly(ADP-ribose) polymerase-1
      activity have antiinflammatory and neuroprotective properties, the present study
      was undertaken to examine the potential antidepressant properties of poly(ADP
      ribose) polymerase inhibitors. Methods: Two rodent models, the Porsolt swim test
      and repeated exposure to psychological stressors, were used to test the poly(ADP
      ribose) polymerase inhibitor, 3-aminobenzamide, for potential antidepressant
      activity. Another poly(ADP-ribose) polymerase inhibitor, 5-aminoisoquinolinone,
      was also tested. Results: Poly(ADP-ribose) polymerase inhibitors produced
      antidepressant-like effects in the Porsolt swim test, decreasing immobility time,
      and increasing latency to immobility, similar to the effects of fluoxetine. In
      addition, 3-aminobenzamide treatment increased sucrose preference and social
      interaction times relative to vehicle-treated control rats following repeated
      exposure to combined social defeat and unpredictable stress, mediating effects
      similar to fluoxetine treatment. Conclusions: The poly(ADP-ribose) polymerase
      inhibitors 3-aminobenzamide and 5-aminoisoquinolinone exhibit antidepressant-like
      activity in 2 rodent stress models and uncover poly(ADP-ribose) polymerase as a
      unique molecular target for the potential development of a novel class of
      antidepressants.

PMID- 29016796
TI  - Empowerment of athletes with cardiac disorders: a new paradigm.
AB  - Athletes with cardiac disorders frequently pose an ethical and medical dilemma to
      physicians assessing their eligibility to participate in sport. In recent
      decades, patient empowerment has been gaining increasing recognition in clinical
      decision-making. Empowerment is a process through which people are involved over
      the decisions and actions that affect their own lives. In the context of a
      cardiac disorder, empowerment means giving an athlete the chance to participate
      in the decision about whether or not to remain active in competition. Three
      models of treatment decision-making are described in this article, with
      progressive levels of empowerment: the paternalistic model (the athlete has a
      passive role), the shared-decision making model (both athlete and physician
      participate in the decision), and the informed-decision making (the decision is
      made by the athlete while the role of the physician is solely to provide
      information). This article critically discusses the issues involved in
      disqualification of athletes with cardiovascular disorders and suggests possible
      ways of incorporating patient empowerment in potentially career-ending decisions.
      The authors propose a model of empowerment, which gives patients the opportunity
      to choose how much, and if, they would like to be involved in the decision-making
      process.

PMID- 29016797
TI  - Multiple clinical profiles of families with the short QT syndrome.
AB  - Aims: Short QT syndrome (SQTS) is a rare cardiac channelopathy characterized by a
      shortened corrected QT (QTc)-interval that can lead to ventricular arrhythmias
      and sudden cardiac death. The aim of this study was to investigate the clinical
      phenotypes and long-term outcomes of three families harbouring genetic mutations
      associated with the SQTS. Methods and results: Clinical data included medical
      history, physical examination, 12-lead ECG, 24-h Holter-ECG, and transthoracic
      echocardiography from three index patients and their first-degree relatives. Next
      generation clinical exome sequencing and genetic cascade screening were performed
      in index patients and their relatives, respectively. Two index patients
      experienced malignant ventricular arrhythmias and one patient suffered from
      arrhythmogenic syncope during a median follow-up period of 8 years. They all had
      genetic mutations associated with the SQTS. Two mutations were found in the KCNH2
      gene, and one in the CACNA2D gene. One patient had an additional SCN10A variant.
      Alive and mutation-positive family members had short QTc-intervals, but no
      further phenotypic manifestations. None of the mutation-negative family members
      had an abnormal ECG or any symptoms. In all patients with shortened QTc
      intervals, the QTc-interval had a low long-term variability and QTc shortening
      always remained detectable by 12-lead ECG. Conclusion: This study shows the
      variety of phenotypic manifestations in different families with SQTS. It further
      emphasizes the importance of a 12-lead ECG for early diagnosis, and the utility
      of next generation sequencing for the identification of mutations associated with
      the SQTS.

PMID- 29016795
TI  - Leonurine Exerts Antidepressant-Like Effects in the Chronic Mild Stress-Induced
      Depression Model in Mice by Inhibiting Neuroinflammation.
AB  - Background: Leonurine is an active alkaloid that is extracted from Traditional
      Chinese Medicine Herba leonuri. Emerging evidence indicates that leonurine
      produces neuroprotective effects in ischemic stroke, Parkinson's disease, and
      Alzheimer's disease. However, the effect of leonurine in neuropsychiatric
      disorders, especially in major depression, remains unknown. Methods: We used the
      chronic mild stress mouse model to explore the antidepressant effects of
      leonurine and the potential mechanisms. Behavioral tests including sucrose
      preference test, forced swimming test, and tail suspension test were taken to
      evaluate depression symptoms. Moreover, the contents of monoamine
      neurotransmitters in hippocampus and prefrontal cortex were measured by high
      performance liquid chromatography. Neuronal morphology was detected by
      transmission electron microscopy. Results: Administration of leonurine (60 mg/kg)
      for 4 weeks significantly alleviated depression-like behaviors of chronic mild
      stress mice, including increased sucrose preference and reduced immobility time
      in forced swimming test and tail suspension test. We further found that leonurine
      (60 mg/kg) effectively restored the levels of 5-hydroxytryptamine, noradrenaline,
      and dopamine in the hippocampus and prefrontal cortex of chronic mild stress
      mice, accompanied by amelioration of hippocampal neuronal damage. Furthermore,
      leonurine (60 mg/kg) significantly inhibited the production of proinflammatory
      cytokine interleukin-1beta, interleukin-6 and TNF-alpha, and suppressed the
      nuclear factor kappa B signaling pathway. Conclusions: These findings demonstrate
      that leonurine exerts antidepressant-like effects, which may be mediated, at
      least in part, by improving monoamine neurotransmitters and inhibiting
      neuroinflammation. Our study provides insight into the potential of leonurine in
      depression therapy.

PMID- 29016798
TI  - Broad Phylogenetic Occurrence of the Oxygen-Binding Hemerythrins in Bilaterians.
AB  - Animal tissues need to be properly oxygenated for carrying out catabolic
      respiration and, as such, natural selection has presumably favored special
      molecules that can reversibly bind and transport oxygen. Hemoglobins,
      hemocyanins, and hemerythrins (Hrs) fulfill this role, with Hrs being the least
      studied. Knowledge of oxygen-binding proteins is crucial for understanding animal
      physiology. Hr genes are present in the three domains of life, Archaea, Bacteria,
      and Eukaryota; however, within Animalia, Hrs has been reported only in marine
      species in six phyla (Annelida, Brachiopoda, Priapulida, Bryozoa, Cnidaria, and
      Arthropoda). Given this observed Hr distribution, whether all metazoan Hrs share
      a common origin is circumspect. We investigated Hr diversity and evolution in
      metazoans, by employing in silico approaches to survey for Hrs from of 120
      metazoan transcriptomes and genomes. We found 58 candidate Hr genes actively
      transcribed in 36 species distributed in 11 animal phyla, with new records in
      Echinodermata, Hemichordata, Mollusca, Nemertea, Phoronida, and Platyhelminthes.
      Moreover, we found that "Hrs" reported from Cnidaria and Arthropoda were not
      consistent with that of other metazoan Hrs. Contrary to previous suggestions that
      Hr genes were absent in deuterostomes, we find Hr genes present in deuterostomes
      and were likely present in early bilaterians, but not in nonbilaterian animal
      lineages. As expected, the Hr gene tree did not mirror metazoan phylogeny,
      suggesting that Hrs evolutionary history was complex and besides the oxygen
      carrying capacity, the drivers of Hr evolution may also consist of secondary
      functional specializations of the proteins, like immunological functions.

PMID- 29016800
TI  - The prognostic impact of single extra-stimulus on programmed ventricular
      stimulation in Brugada patients without previous cardiac arrest: multi-centre
      study in Japan.
AB  - Aims: The prognostic value of programmed electrical stimulation (PES) in Brugada
      syndrome (BrS) remains controversial. One of the reasons for discrepant results
      may be due to the selection of stimulation protocol. We evaluated the prognostic
      value of a positive PES result (PES+) according to the inducible pacing sites and
      the number of extra-stimuli in BrS patients without previous cardiac arrest (CA).
      Methods and results: We enrolled 224 consecutive BrS patients without previous CA
      (mean age 51 +/- 14 years, 209 males), who underwent PES with the identical
      protocol. Clinical outcomes of development of CA were explored in the patients
      with and without PES+ according to sites and number of extra-stimuli. During a
      mean follow-up period of 76 months, 12 cardiac events (CE: sudden cardiac death
      or documented VF) occurred (8 with and 4 without PES+). The incidence of CE was
      not different in patients with and without PES+, those with PES+ from RVA (n =
      72) or RVOT (n = 60), and those with and without PES+ by up to 2 extra-stimuli (n
      = 58). However, in patients that were PES+ by a single extra-stimulus (n = 8) the
      incidence of CE was significantly higher than in those without PES+ (8.8 vs.
      0.6%/year, P < 0.0001). On univariate analysis, syncope, spontaneous type 1 ECG,
      and PES+ by a single extra-stimulus were associated with CE. Conclusion: Details
      of the stimulation protocol may be important for risk assessment in BrS patients
      without previous CA. A single extra-stimulus may be useful in stratifying risk in
      patients with spontaneous type 1 ECG and syncope.

PMID- 29016801
TI  - Guerra F, et al. Symptomatic atrial fibrillation and risk of cardiovascular
      events: data from the Euro Heart Survey.

PMID- 29016799
TI  - Signatures of Selection and Interspecies Introgression in the Genome of Chinese
      Domestic Pigs.
AB  - Chinese domestic pigs have experienced strong artificial selection for thousands
      of years. However, the molecular mechanisms underlying the selection-causing
      phenotypic changes in Chinese domestic pigs are still largely unknown. Here we
      used whole-genome resequencing data of 54 pigs from 9 Chinese diverse breeds and
      16 wild boars from 7 localities across China to identify genes that show evidence
      of positive selection in the process of domestication. A total of 14 candidate
      domestication regions were detected by selective sweep analyses of genetic
      differentiation and variability, and a set of genes in these candidate
      domestication regions were found to be related to metabolic process, development,
      reproduction, olfactory, behavior, and nervous system. The most promising
      candidate gene under selection - TBX19 - probably underlies the metabolic
      alteration and developmental traits, and may also associate with timidity of
      Chinese domestic pigs. Intriguingly, we found that the haplotype at TBX19 locus
      shared by nearly all Chinese domestic pigs was possibly introgressed from another
      Sus species. We also revealed the AHR gene associated with female reproduction is
      under strong positive selection. These results advance our understanding of the
      evolutionary history of Chinese domestic pigs and shed insights into identifying
      functionally important genes/mutations contributing to the phenotypic diversity
      in pigs.

PMID- 29016803
TI  - The bipolar ablation of refractory typical atrial flutter with CARTO 3 Confidense
      system.

PMID- 29016802
TI  - Intra-atrial re-entrant tachycardia in congenital heart disease: types and
      relation of isthmus to atrial voltage.
AB  - Background: Intra-atrial re-entrant tachycardia (IART) is a frequent and severe
      complication in patients with congenital heart disease (CHD). Cavotricuspid
      isthmus (CTI)-related IART is the most frequent mechanism. However, due to
      fibrosis and surgical scars, non-CTI-related IART is also frequent. Objective:
      The main objective of this study was to describe the types of IART and circuit
      locations and to define a cut-off value for unhealthy tissue in the atria.
      Methods and results: This observational study included all consecutive patients
      with CHD who underwent a first ablation procedure for IART from January 2009 to
      December 2015 (94 patients, 39.4% female, age: 36.55 +/- 14.9 years, 40.4% with
      highly complex cardiac disease). During the study, 114 IARTs were ablated (1.21
      +/- 0.41 IARTs per patient). Cavotricuspid isthmus-related IART was the only
      arrhythmia in 51% (n = 48) of patients, non-CTI-related IART was the only
      mechanism in 27.7% (n = 26), and 21.3% of patients (n = 20) presented both types
      of IART. In cases of non-CTI-related IART, the most frequent location of IART
      isthmus was the lateral or posterolateral wall of the venous atria, and a voltage
      cut-off value for unhealthy tissue in the atria of 0.5 mV identified 95.4% of
      IART isthmus locations. Conclusion: In our population with a high proportion of
      complex CHD, CTI-related IART was the most frequent mechanism, although non-CTI
      related IART was present in 49% of patients (alone or with concomitant CTI
      related IART). A cut-off voltage of 0.5 mV could identify 95.4% of the substrates
      in non-CTI-related IART.

PMID- 29016804
TI  - The double adenosine test: a simple and non-invasive tip to unmask unapparent pre
      excitations: an example of Mahaim fibres.

PMID- 29016805
TI  - Dissecting human gliomas by single-cell RNA sequencing.
AB  - Diffuse gliomas are the most common human primary brain tumors and remain
      incurable. They are complex entities in which diverse genetic and nongenetic
      effects determine tumor biology and clinical course. Our current understanding of
      gliomas in patients is primarily based on genomic and transcriptomic methods that
      have profiled them as bulk, providing critical information yet masking the
      diversity of cells within each tumor. Recent advances in single-cell DNA and RNA
      profiling have paved the way to studying tumors at cellular resolution. Here, we
      review initial studies deploying single-cell analysis in clinical glioma samples,
      with a focus on RNA expression profiling. We highlight how these studies provide
      new insights into glioma biology, tumor heterogeneity, cancer cell lineages,
      cancer stem cell programs, the tumor microenvironment, and glioma classification.

PMID- 29016806
TI  - Differential Patterns of Subcortical Activity Evoked by Glial GLT-1 Blockade in
      Prelimbic and Infralimbic Cortex: Relationship to Antidepressant-Like Effects in
      Rats.
AB  - Background: Glutamatergic neurotransmission has emerged as a novel target in
      antidepressant drug development, with a critical role of the ventral anterior
      cingulate cortex. We recently reported that blockade of the astrocytic glutamate
      transporter GLT-1 with dihydrokainic acid in infralimbic cortex (rodent
      equivalent of ventral anterior cingulate cortex), but not in the adjacent
      prelimbic cortex, evoked robust antidepressant-like effects through alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid receptor activation and increased
      serotonin release. Methods: 2-deoxy-2-[18F]-fluoro-D-glucose-positron emission
      tomography and computed tomography in 36 male Wistar rats microinfused
      bilaterally in prelimbic cortex or infralimbic cortex with dihydrokainic acid or
      vehicle. Results: Dihydrokainic acid microinfusion in infralimbic cortex and
      prelimbic cortex evoked dramatically different regional patterns of subcortical
      activity. In infralimbic cortex, dihydrokainic acid selectively affected midbrain
      areas, whereas in prelimbic cortex it affected the basal ganglia, the thalamus,
      and both superior and inferior colliculi. Conclusions: These results highlight
      the differential connectivity of infralimbic and prelimbic cortex with
      subcortical brain regions and support the involvement of infralimbic cortex
      midbrain pathway in the antidepressant-like effects of dihydrokainic acid.

PMID- 29016807
TI  - A recombinant lentiviral PDGF-driven mouse model of proneural glioblastoma.
AB  - Background: Mouse models of glioblastoma (GBM), the most aggressive primary brain
      tumor, are critical for understanding GBM pathology and can contribute to the
      preclinical evaluation of therapeutic agents. Platelet-derived growth factor
      (PDGF) signaling has been implicated in the development and pathogenesis of GBM,
      specifically the proneural subtype. Although multiple mouse models of PDGF-driven
      glioma have been described, they require transgenic mice engineered to activate
      PDGF signaling and/or impair tumor suppressor genes and typically represent lower
      grade glioma. Methods: We designed recombinant lentiviruses expressing both PDGFB
      and a short hairpin RNA targeting Cdkn2a to induce gliomagenesis following
      stereotactic injection into the dentate gyrus of adult immunocompetent mice. We
      engineered these viruses to coexpress CreERT2 with PDGFB, allowing for deletion
      of floxed genes specifically in transduced cells, and designed another version of
      this recombinant lentivirus in which enhanced green fluorescent protein was
      coexpressed with PDGFB and CreERT2 to visualize transduced cells. Results: The
      dentate gyrus of injected mice showed hypercellularity one week post-injection
      and subsequently developed bona fide tumors with the pathologic hallmarks of GBM
      leading to a median survival of 77 days post-injection. Transcriptomic analysis
      of these tumors revealed a proneural gene expression signature. Conclusion:
      Informed by the genetic alterations observed in human GBM, we engineered a novel
      mouse model of proneural GBM. While reflecting many of the advantages of
      transgenic mice, this model allows for the facile in vivo testing of gene
      function in tumor cells and makes possible the rapid production of large numbers
      of immunocompetent tumor-bearing mice for preclinical testing of therapeutics.

PMID- 29016808
TI  - Molecular differences in IDH wildtype glioblastoma according to MGMT promoter
      methylation.
AB  - Background: O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation
      status is a predictive biomarker in glioblastoma. We investigated whether this
      marker furthermore defines a molecularly distinct tumor subtype with clinically
      different outcome. Methods: We analyzed copy number variation (CNV) and
      methylation profiles of 1095 primary and 92 progressive isocitrate dehydrogenase
      wildtype glioblastomas, including paired samples from 49 patients. DNA mutation
      data from 182 glioblastoma samples of The Cancer Genome Atlas (TCGA) and RNA
      expression from 107 TCGA and 55 Chinese Glioma Genome Atlas samples were
      analyzed. Results: Among untreated glioblastomas, MGMT promoter methylated
      (mMGMT) and unmethylated (uMGMT) tumors did not show different CNV or specific
      gene mutations, but a higher mutation count in mMGMT tumors. We identified 3
      methylation clusters. Cluster 1 showed the highest average methylation and was
      enriched for mMGMT tumors. Seventeen genes including gastrulation brain homeobox
      2 (GBX2) were found to be hypermethylated and downregulated on the mRNA level in
      mMGMT tumors. In progressive glioblastomas, platelet derived growth factor
      receptor alpha (PDGFRA) and GLI2 amplifications were enriched in mMGMT tumors.
      Methylated MGMT tumors gain PDGFRA amplification of PDGFRA, whereas uMGMT tumors
      with amplified PDGFRA frequently lose this amplification upon progression.
      Glioblastoma patients surviving <6 months and with mMGMT harbored less frequent
      epidermal growth factor receptor (EGFR) amplifications, more frequent TP53
      mutations, and a higher tumor necrosis factor-nuclear factor-kappaB (TNF
      NFkappaB) pathway activation compared with patients surviving >12 months.
      Conclusions: MGMT promoter methylation status does not define a molecularly
      distinct glioblastoma subpopulation among untreated tumors. Progressive mMGMT
      glioblastomas and mMGMT tumors of patients with short survival tend to have more
      unfavorable molecular profiles.

PMID- 29016809
TI  - Longitudinal assessment of late-onset neurologic conditions in survivors of
      childhood central nervous system tumors: a Childhood Cancer Survivor Study
      report.
AB  - Background: Survivors of childhood central nervous system (CNS) tumors experience
      high rates of treatment-related neurologic sequelae. Whether survivors continue
      to be at increased risk for new events as they age is unknown. Methods: Adverse
      neurologic health conditions in 5-year survivors of CNS tumors from the Childhood
      Cancer Survivor Study (n = 1876) were evaluated longitudinally at a median 23.0
      years from diagnosis (range, 5.1-38.9), median age at last evaluation 30.3 years
      (range, 6.1-56.4). Multivariable regression estimated hazard ratios (HRs) and 95%
      CIs. Results: From 5 to 30 years post diagnosis, cumulative incidence increased
      for seizures from 27% to 41%, motor impairment 21% to 35%, and hearing loss 9% to
      23%. Risks were elevated compared with siblings (eg, seizures HR: 12.7; 95% CI:
      9.6-16.7; motor impairment HR: 7.6; 95% CI: 5.8-9.9; hearing loss HR: 18.4; 95%
      CI: 13.1-25.9). Regional brain doses of radiation therapy were associated with
      development of new deficits (eg, frontal >=50 Gy and motor impairment HR: 2.0;
      95% CI: 1.2-3.4). Increased risk for motor impairment was also associated with
      tumor recurrence (HR: 2.6; 95% CI: 1.8-3.8), development of a meningioma (HR:
      2.3; 95% CI: 0.9-5.4), and stroke (HR: 14.9; 95% CI: 10.4-21.4). Seizure risk was
      doubled by recurrence (HR: 2.3; 95% CI: 1.6-3.2), meningioma (HR: 2.6; 95% CI:
      1.1-6.5), and stroke (HR: 2.0; 95% CI: 1.1-3.4). Conclusions: CNS tumor survivors
      remain at risk for new-onset adverse neurologic events across their lifespans at
      a rate greater than siblings. Cranial radiation, stroke, tumor recurrence, and
      development of meningioma were independently associated with late-onset adverse
      neurologic sequelae.

PMID- 29016811
TI  - Drone Transport of Chemistry and Hematology Samples Over Long Distances.
AB  - Objectives: We addressed the stability of biological samples in prolonged drone
      flights by obtaining paired chemistry and hematology samples from 21 adult
      volunteers in a single phlebotomy event-84 samples total. Methods: Half of the
      samples were held stationary, while the other samples were flown for 3 hours (258
      km) in a custom active cooling box mounted on the drone. After the flight, 19
      chemistry and hematology tests were performed. Results: Seventeen analytes had
      small or no bias, but glucose and potassium in flown samples showed an 8% and
      6.2% bias, respectively. The flown samples (mean, 24.8 degrees C) were a mean of
      2.5 degrees C cooler than the stationary samples (mean, 27.3 degrees C) during
      transportation to the flight field as well as during the flight. Conclusions: The
      changes in glucose and potassium are consistent with the magnitude and duration
      of the temperature difference between the flown and stationary samples. Long
      drone flights of biological samples are feasible but require stringent
      environmental controls to ensure consistent results.

PMID- 29016810
TI  - miR-30c-5p regulates macrophage-mediated inflammation and pro-atherosclerosis
      pathways.
AB  - Aims: Atherosclerosis is an inflammatory disease wherein cholesterol-loaded
      macrophages play a major role. MicroRNAs and microparticles propagate
      inflammatory pathways and are involved in cardiovascular disease. We aimed to
      screen and validate circulating microRNAs correlated with atherosclerosis
      development in humans, and to dissect the molecular mechanisms associated with
      atherogenesis using in vitro and in vivo approaches. Methods and results: A panel
      of 179 secreted microRNAs was screened in plasma samples of patients with and
      without atherosclerosis, and validated cross-sectionally and prospectively in
      patients followed for up to 11 years. miR-30c-5p was inversely correlated with
      total and LDL cholesterol, carotid intimal media thickness (CIMT), presence and
      future development of plaques. Using a human macrophage line and in vitro gene
      silencing strategies, we found that miR-30c-5p was downregulated by oxidized LDL
      (oxLDL) via the scavenger receptor CD36 and inhibition miR processing by Dicer.
      In turn, miR-30c-5p downregulation was responsible for the effects of oxLDL on
      macrophage IL-1beta release, caspase-3 expression, and apoptosis. miR-30c-5p
      loaded into microparticles was uptaken by macrophages and regulated target genes,
      like caspase-3, at transcriptional level. To establish the relevance of this
      pathway on endothelial damage as the earliest step of atherogenesis, we show that
      systemic miR-30c-5p knockdown induced caspase-3 and impaired endothelial healing
      after carotid injury in C57Bl/6 J mice. Conclusions: With an unbiased screening
      of secreted microRNAs, we identify reduction of miR-30c-5p in microparticles as a
      promoter of early atherosclerosis, by conveying pro-inflammatory pro-apoptotic
      signals and impairing endothelial healing. Therefore, stimulation of miR-30c-5p
      is a candidate direct anti-atherosclerotic therapy.

PMID- 29016812
TI  - Brain volume reduction after whole-brain radiotherapy: quantification and
      prognostic relevance.
AB  - Background: Recent studies have questioned the value of adding whole-brain
      radiotherapy (WBRT) to stereotactic radiosurgery (SRS) for brain metastasis
      treatment. Neurotoxicity, including radiation-induced brain volume reduction,
      could be one reason why not all patients benefit from the addition of WBRT. In
      this study, we quantified brain volume reduction after WBRT and assessed its
      prognostic significance. Methods: Brain volumes of 91 patients with cerebral
      metastases were measured during a 150-day period after commencing WBRT and were
      compared with their pretreatment volumes. The average daily relative change in
      brain volume of each patient, referred to as the "brain volume reduction rate,"
      was calculated. Univariate and multivariate Cox regression analyses were
      performed to assess the prognostic significance of the brain volume reduction
      rate, as well as of 3 treatment-related and 9 pretreatment factors. A one-way
      analysis of variance was used to compare the brain volume reduction rate across
      recursive partitioning analysis (RPA) classes. Results: On multivariate Cox
      regression analysis, the brain volume reduction rate was a significant predictor
      of overall survival after WBRT (P < 0.001), as well as the number of brain
      metastases (P = 0.002) and age (P = 0.008). Patients with a relatively favorable
      prognosis (RPA classes 1 and 2) experienced significantly less brain volume
      decrease after WBRT than patients with a poor prognosis (RPA class 3) (P =
      0.001). There was no significant correlation between delivered radiation dose and
      brain volume reduction rate (P = 0.147). Conclusion: In this retrospective study,
      a smaller decrease in brain volume after WBRT was an independent predictor of
      longer overall survival.

PMID- 29016813
TI  - Epicardial left atrial appendage AtriClip occlusion reduces the incidence of
      stroke in patients with atrial fibrillation undergoing cardiac surgery.
AB  - Aims: Left atrial appendage (LAA) occlusion has emerged as an interesting
      alternative to oral anticoagulation (OAC) for stroke prevention in patients with
      atrial fibrillation (AF). We report the safety, efficacy, and durability of
      concomitant device-enabled epicardial LAA occlusion during open-heart surgery. In
      addition to long-term follow-up, we evaluate the impact on stroke risk in this
      selected population. Methods and results: A total of 291 AtriClip devices were
      deployed epicardially in patients (mean CHA2DS2-VASc-Score: 3.1 +/- 1.5)
      undergoing open-heart surgery (including isolated coronary artery bypass
      grafting, valve, or combined procedures) comprising of forty patients from a
      first-in-man device trial (NCT00567515) and 251 patients from a consecutive
      institutional registry thereafter. In all patients (n = 291), the LAA was
      successfully excluded and overall mean follow-up (FU) was 36 +/- 23months (range:
      1-97 months). No device-related complications were detected throughout the FU
      period. Long-term imaging work-up (computed tomography) in selected patients
      >=5years post-implant (range: 5.1-8.1 years) displayed complete LAA occlusion
      with no signs of residual reperfusion or significant LAA stumps. Subgroup
      analysis of patients with discontinued OAC during FU (n = 166) revealed a
      relative risk reduction of 87.5% with an observed ischaemic stroke-rate of
      0.5/100 patient-years compared with what would have been expected in a group of
      patients with similar CHA2DS2-VASc scores (expected rate of 4.0/100 patient
      years). No strokes occurred in the subgroup with OAC. Conclusion: The long-term
      results from our first-in-man prospective human trial plus our institutional
      registry of epicardial LAA occlusion with the AtriClip in patients with AF
      undergoing cardiac surgery demonstrate the safety and durability of the
      procedure. In addition, our data are suggestive for the potential efficacy of LAA
      occlusion in reducing the incidence of stroke. If validated in future large
      randomized trials, routine LAA occlusion in patients undergoing cardiac surgery
      (with contraindications to treatment with oral anticoagulants) may represent a
      reasonable adjunct procedure to reduce the risk of future stroke. Clinical Trial
      Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00567515.

PMID- 29016814
TI  - Early posttreatment assessment of MRI perfusion biomarkers can predict long-term
      response of lung cancer brain metastases to stereotactic radiosurgery.
AB  - Background: Imaging criteria to evaluate the response of brain metastases to
      stereotactic radiosurgery (SRS) in the early posttreatment period remains a
      crucial unmet need. The aim of this study is to correlate early (within 12 wk)
      posttreatment perfusion MRI changes with long-term outcomes after treatment of
      lung cancer brain metastases with SRS. Methods: Pre- and posttreatment perfusion
      MRI scans were obtained in patients treated with SRS for intact non-small cell
      lung cancer brain metastases. Time-dependent leakage (Ktrans), blood plasma
      volume (Vp), and extracellular extravascular volume (Ve) were calculated for each
      lesion. Patients were followed longitudinally with serial MRI until death,
      progression, or intervention (whole brain radiation or surgery). Results: We
      included 53 lesions treated with SRS from 41 total patients. Median follow-up
      after treatment was 11 months. Actuarial local control at one year was 85%.
      Univariate analysis demonstrated a significant difference (P = 0.032) in
      posttreatment Ktrans SD between patients with progressive disease (mean = 0.0317)
      and without progressive disease (mean = 0.0219). A posttreatment Ktrans SD cutoff
      value of 0.017 was highly sensitive (89%) for predicting progressive disease and
      no progressive disease. Early posttreatment volume change was not associated with
      outcome (P = 0.941). Conclusion: Posttreatment Ktrans SD may be used as an early
      posttreatment imaging biomarker to help predict long-term response of lung cancer
      brain metastases to SRS. This can help identify patients who will ultimately fail
      SRS and allow for timelier adjustment in treatment approach. These data should be
      prospectively validated in larger patient cohorts and other histologies.

PMID- 29016817
TI  - Association between socioeconomic factors and ICD implantation in a publicly
      financed health care system: a Danish nationwide study.
AB  - Aims: For patients surviving out-of-hospital cardiac arrest (OHCA) with a
      shockable rhythm, implantable cardioverter defibrillator (ICD) is recommended for
      non-reversible causes of arrest. We aimed to determine factors associated with
      implantation of ICD and survival in patients surviving non-AMI OHCA in a
      nationwide register covering all OHCAs in Denmark. Methods and results: We
      identified 36 950 OHCAs between 2001 and 2012, 1700 of whom were ICD naive, >=18
      years, of non-AMI cardiac aetiology and surviving until discharge. Six hundred
      fifty eight patients had ICD implanted during index admission. Association to ICD
      implantation during index admission was analysed in logistic regression, survival
      was assessed using Cox regression. Implantable cardioverter defibrillator
      implantation increased during the study period [odds ratio (OR) 1-year increase:
      1.04, 95% confidence intervals (95% CI): 1.00-1.08, P = 0.03]. Non-shockable
      rhythm and age >=70 years were associated with lower odds of ICD implantation
      (ORnon-shockable: 0.27, 95% CI: 0.19-0.37, P < 0.001, OR70-79 years: 0.71, 95%
      CI: 0.52-0.98, P = 0.04, OR>=80 years: 0.13, 95% CI: 0.07-0.22, P < 0.001). Non
      AMI ischaemic heart disease, highest income tertile and chronic heart failure
      were associated with higher odds (ORIHD: 2.51, 95% CI: 1.77-3.60, P < 0.001,
      ORhighest income tertile: 1.58, 95% CI: 1.06-2.23, P = 0.02, ORHF: 1.77, 95% CI:
      1.35-2.32, P < 0.001). Implantable cardioverter defibrillator implantation was
      associated with a lower risk of mortality (HR: 0.70, 95% CI: 0.53-0.92, P =
      0.01). Conclusion: Implantable cardioverter defibrillator implantation rates
      increased over the study period. CHF, previous IHD and high income were
      associated with ICD implantation, while older age and non-shockable rhythm was
      associated with lower odds of ICD implantation. Implantable cardioverter
      defibrillator implantation was associated with higher survival rates.

PMID- 29016815
TI  - Glioblastoma in elderly patients: solid conclusions built on shifting sand?
AB  - Management of glioblastoma in the elderly population is challenging. In the near
      future, more than half of patients with this tumor will be over the age of 65.
      Clinicians have been historically reluctant to treat such patients with the same
      intensity as younger patients. Due to upper age limits or poor accrual of elderly
      patients in clinical trials, randomized data for this patient population have
      been relatively sparse until recently. In this review, we will discuss the
      concept of an elderly patient population, describe evidence for molecular
      differences in glioblastoma of elderly versus young patients, evaluate recent
      first-line trials studying glioblastoma in elderly patients, and discuss best
      therapeutic practices including the value of molecular testing.

PMID- 29016819
TI  - Tissue specificity of in vitro drug sensitivity.
AB  - Objectives: We sought to investigate the tissue specificity of drug sensitivities
      in large-scale pharmacological studies and compare these associations to those
      found in drug clinical indications. Materials and Methods: We leveraged the
      curated cell line response data from PharmacoGx and applied an enrichment
      algorithm on drug sensitivity values' area under the drug dose-response curves
      (AUCs) with and without adjustment for general level of drug sensitivity.
      Results: We observed tissue specificity in 63% of tested drugs, with 8% of total
      interactions deemed significant (false discovery rate <0.05). By restricting the
      drug-tissue interactions to those with AUC > 0.2, we found that in 52% of
      interactions, the tissue was predictive of drug sensitivity (concordance index >
      0.65). When compared with clinical indications, the observed overlap was weak
      (Matthew correlation coefficient, MCC = 0.0003, P > .10). Discussion: While drugs
      exhibit significant tissue specificity in vitro, there is little overlap with
      clinical indications. This can be attributed to factors such as underlying
      biological differences between in vitro models and patient tumors, or the
      inability of tissue-specific drugs to bring additional benefits beyond gold
      standard treatments during clinical trials. Conclusion: Our meta-analysis of pan
      cancer drug screening datasets indicates that most tested drugs exhibit tissue
      specific sensitivities in a large panel of cancer cell lines. However, the
      observed preclinical results do not translate to the clinical setting. Our
      results suggest that additional research into showing parallels between
      preclinical and clinical data is required to increase the translational potential
      of in vitro drug screening.

PMID- 29016820
TI  - Selective BCL-XL inhibition promotes apoptosis in combination with MLN8237 in
      medulloblastoma and pediatric glioblastoma cells.
AB  - Background: CNS tumors, including medulloblastoma and pediatric glioblastoma
      (pGBM) account for the majority of solid pediatric malignancies. There remains an
      unmet need to identify novel treatment approaches in poor prognosis and relapsed
      pediatric brain tumors, where therapeutic options are limited. Small-molecule B
      cell lymphoma 2 (BCL-2) family inhibitors may enhance tumor cell killing when
      combined with conventional and targeted chemotherapeutic agents. We investigated
      the effect of disrupting BCL-2 and B cell lymphoma-extra large (BCL-XL) protein
      function using ABT-263, ABT-199 and WEHI-539 in medulloblastoma and pGBM cells
      following treatment with MLN8237, an Aurora kinase inhibitor under investigation
      as a novel agent for the treatment of malignant brain tumors. Methods: Tumor cell
      growth and viability were determined by MTT/WST-1 assays and flow cytometry.
      Effects on cell phenotype, cell cycle progression, and ploidy were determined by
      live cell imaging and DNA content analysis. Apoptosis was determined by annexin
      V/propidium iodide staining and time-lapse microscopy and confirmed by measuring
      caspase-3/7 activity and western blotting and by short interfering RNA (siRNA)
      knockdown of BCL-2 associated X protein/BCL-2 antagonist killer (BAX/BAK).
      Results: ABT-263, in combination with MLN8237, reduced mitotic slippage and
      polyploidy and promoted the elimination of mitotically defective cells via a
      BAX/BAK-dependent, caspase-mediated apoptotic pathway. The BCL-XL antagonist,
      WEHI-539, significantly augmented tumor cell killing when used in combination
      with MLN8237, as well as sensitized resistant brain tumor cells to a novel BAX
      activator, SMBA1. In addition, siRNA-mediated knockdown of BCL-XL sensitized pGBM
      and medulloblastoma cells to MLN8237 and mimicked the effect of combination drug
      treatment. Conclusion: Selective small-molecule inhibitors of BCL-XL may enhance
      the efficacy of MLN8237 and other targeted chemotherapeutic agents.

PMID- 29016818
TI  - Posterior fossa syndrome and long-term neuropsychological outcomes among children
      treated for medulloblastoma on a multi-institutional, prospective study.
AB  - Background: Patients treated for medulloblastoma who experience posterior fossa
      syndrome (PFS) demonstrate increased risk for neurocognitive impairment at one
      year post diagnosis. The aim of the study was to examine longitudinal
      trajectories of neuropsychological outcomes in patients who experienced PFS
      compared with patients who did not. Methods: Participants were 36 patients (22
      males) who experienced PFS and 36 comparison patients (21 males) who were matched
      on age at diagnosis and treatment exposure but did not experience PFS. All
      patients underwent serial evaluation of neurocognitive functioning spanning 1 to
      5 years post diagnosis. Results: The PFS group demonstrated lower estimated mean
      scores at 1, 3, and 5 years post diagnosis on measures of general intellectual
      ability, processing speed, broad attention, working memory, and spatial relations
      compared with the non-PFS group. The PFS group exhibited estimated mean scores
      that were at least one standard deviation below the mean for intellectual
      ability, processing speed, and broad attention across all time points and for
      working memory by 5 years post diagnosis. Processing speed was stable over time.
      Attention and working memory declined over time. Despite some change over time,
      caregiver ratings of executive function and behavior problem symptoms remained
      within the average range. Conclusion: Compared with patients who do not
      experience PFS, patients who experience PFS exhibit greater neurocognitive
      impairment, show little recovery over time, and decline further in some domains.
      Findings highlight the particularly high risk for long-term neurocognitive
      problems in patients who experience PFS and the need for close follow-up and
      intervention.

PMID- 29016821
TI  - Super-response to cardiac resynchronization therapy reduces appropriate
      implantable cardioverter defibrillator therapy.
AB  - Aims: To determine the frequency of implantable cardioverter defibrillator (ICD)
      therapy following cardiac resynchronization therapy (CRT-D) implantation in super
      and non-super responders and whether greater improvement in left ventricular (LV)
      function after CRT is associated with a reduced burden in ICD therapy. Methods
      and results: This is a two-centre, retrospective study between January 2002 and
      September 2011. Patients were classified as non-super responders and super
      responders based on the post-CRT ejection fraction (EF) of < 50% and >=50%,
      respectively. Of 629 recipients of CRT-D, 37 (5.9%) were super-responders.
      Implantable cardioverter defibrillator follow-up was available for a mean
      duration of 6.2 +/- 2.7 years. The 5-year rate of antitachycardia pacing (ATP) in
      super-responders was significantly lower than in non-super responders (2.7% vs.
      22.1%, P = 0.004). Super-responders also had a lower 5-year rate of appropriate
      ICD shock compared with non-super responders (2.7% vs. 14.3%, P = 0.03). On
      multivariable analysis, factors associated with appropriate ICD therapy (ICD
      shock/ATP) include male gender (hazard ratio, HR 1.97, 95% confidence interval,
      95% CI 1.15-3.35), secondary prevention indication (HR 2.09, 95% CI 1.13-3.85),
      increased baseline LV end-systolic diameter (HR 1.03 per mm, 95% CI 1.01-1.06)
      and higher baseline EF (HR 1.03 per %, 95% CI 1.00-1.06) while super-responder
      status was highly protective (HR 0.13, 95% CI 0.02-0.91). Conclusion: Recipients
      of CRT-D that normalize their EF have very low rates of ventricular arrhythmias
      requiring appropriate ICD therapy compared with those that do not.

PMID- 29016816
TI  - Molecular and Epigenetic Mechanisms for the Complex Effects of Stress on Synaptic
      Physiology and Cognitive Functions.
AB  - Evidence over the past decades has found that stress, particularly through the
      corticosterone stress hormones, produces complex changes in glutamatergic
      signaling in prefrontal cortex, which leads to the alteration of cognitive
      processes medicated by this brain region. Interestingly, the effects of stress on
      glutamatergic transmission appear to be "U-shaped," depending upon the duration
      and severity of the stressor. These biphasic effects of acute vs chronic stress
      represent the adaptive vs maladaptive responses to stressful stimuli. Animal
      studies suggest that the stress-induced modulation of excitatory synaptic
      transmission involves changes in presynaptic glutamate release, postsynaptic
      glutamate receptor membrane trafficking and degradation, spine structure and
      cytoskeleton network, and epigenetic control of gene expression. This review will
      discuss current findings on the key molecules involved in the stress-induced
      regulation of prefrontal cortex synaptic physiology and prefrontal cortex
      mediated functions. Understanding the molecular and epigenetic mechanisms that
      underlie the complex effects of stress will help to develop novel strategies to
      cope with stress-related mental disorders.

PMID- 29016823
TI  - The effect of cardiorespiratory fitness assessment in preventive health checks: a
      randomised controlled trial.
AB  - Background: Poor cardiorespiratory fitness (CRF) increases morbidity and
      mortality risks. Routine CRF assessment in clinical practice has thus been
      advocated, but little is known about the effect. In this study, we investigated
      the effect of CRF assessment on CRF in a preventive health check programme.
      Methods: We used a randomised design, in which we invited 4153 middle-aged adults
      and included 2201 participants who received a preventive health check with CRF
      assessment (intervention) or without CRF assessment (control). After 1 year,
      participants were examined. The primary outcomes were adjusted absolute (l/min),
      relative (ml/kg/min), and poor (%) CRF assessed by the Astrand-Ryhming test. We
      adjusted for baseline physical activity and intra-cluster correlation within
      general practices. Results: A total of 901 attended the 1-year follow-up. In the
      intervention group, absolute CRF, relative CRF, and poor CRF were 2.7 l/min (95%
      confidence interval [CI]: 2.6; 2.8), 34.5 ml/kg/min (95% CI: 33.5; 35.4), and
      31.0% (95% CI: 26.8; 35.2). In the control group, the corresponding figures were
      2.8 l/min (95% CI: 2.7; 2.9), 35.2 ml/kg/min (95% CI: 34.2; 36.1), and 25.9% (95%
      CI: 21.8; 30.0). Adjusted absolute CRF was lower in the intervention group (-0.1
      l/min [95% CI: -0.2; -0.01]). Adjusted relative CRF (-0.7 ml/kg/min [95% CI: 
      2.0; 0.6]) and poor CRF (5.0% [95% CI: -0.002; 10.1]) did not differ between
      groups. No differences were found when adjusting for potential confounding
      factors. Conclusion: Preventive health checks with CRF assessment did not provide
      higher CRF levels at 1-year follow-up than preventive health checks without CRF
      assessment.

PMID- 29016822
TI  - Platelet-Derived Growth Factor as an Antidepressant Treatment Selection
      Biomarker: Higher Levels Selectively Predict Better Outcomes with Bupropion-SSRI
      Combination.
AB  - Background: Platelet derived growth factor is integral to maintenance of blood
      brain barrier, increases in response to blood brain barrier disruption, and may
      reflect neuroinflammation. Based on previous reports of better outcomes with
      dopaminergic antidepressants in depressed patients with elevated inflammatory
      biomarkers, we hypothesize that elevated peripheral platelet derived growth
      factor levels can serve as a powerful biomarker for selecting dopaminergic
      antidepressants. Methods: Platelet derived growth factor, basic fibroblast growth
      factor, and granulocyte colony stimulating factor were measured as part of
      Bioplex Pro human cytokine 27-plex kit in participants of the Combining
      Medications to Enhance Depression Outcomes trial who provided baseline plasma
      (n=166) and were treated with either bupropion-plus-escitalopram, escitalopram
      plus-placebo, or venlafaxine-plus-mirtazapine. Differential changes in overall
      symptom severity and anhedonia as well as side effects were tested with a
      treatment-arm-by-biomarker interaction in mixed model analyses. Effect of
      biomarkers with significant interaction was calculated in subsequent analyses
      stratified by treatment arm. Results: There was a significant treatment-arm-by
      platelet derived growth factor interaction for depression severity (P=.03) and
      anhedonia (P=.008) but not for side effects (P=.44). Higher baseline platelet
      derived growth factor level was associated with greater reduction in depression
      severity (effect size=0.71, P=.015) and anhedonia (effect size=0.66, P=.02) in
      the bupropion- selective serotonin reuptake inhibitor but not the other two
      treatment arms. There was no significant treatment-arm-by-biomarker interaction
      for both depression severity and side effects with the other two biomarkers.
      Conclusion: As compared with selective serotonin reuptake inhibitor monotherapy
      or venlafaxine-plus-mirtazapine, bupropion-plus-escitalopram selectively improves
      anhedonia, which in turn results in improved overall depression severity in
      depressed patients with elevated platelet derived growth factor levels.

PMID- 29016825
TI  - NLPReViz: an interactive tool for natural language processing on clinical text.
AB  - The gap between domain experts and natural language processing expertise is a
      barrier to extracting understanding from clinical text. We describe a prototype
      tool for interactive review and revision of natural language processing models of
      binary concepts extracted from clinical notes. We evaluated our prototype in a
      user study involving 9 physicians, who used our tool to build and revise models
      for 2 colonoscopy quality variables. We report changes in performance relative to
      the quantity of feedback. Using initial training sets as small as 10 documents,
      expert review led to final F1scores for the "appendiceal-orifice" variable
      between 0.78 and 0.91 (with improvements ranging from 13.26% to 29.90%). F1for
      "biopsy" ranged between 0.88 and 0.94 (-1.52% to 11.74% improvements). The
      average System Usability Scale score was 70.56. Subjective feedback also suggests
      possible design improvements.

PMID- 29016826
TI  - Emotion-regulation ability, role stress and teachers' mental health.
AB  - Background: Work-related stressors, including role ambiguity and role conflict,
      are related to psychological maladjustment and mental ill-health. However, to
      date, the role of personal resources such as emotion-regulation ability (ERA) in
      the prediction of mental health indicators has not been addressed. Aims: To
      examine whether ERA would contribute to explaining teachers' depression, anxiety
      and stress symptoms beyond role ambiguity and role conflict. Methods: We carried
      out a cross-sectional questionnaire survey. We used a correlation matrix and
      hierarchical regression models to analyse the data. Results: Three hundred and
      thirty-six Spanish teachers (185 female) from several grade levels completed the
      surveys (40% response rate). Role ambiguity and role conflict were positively
      related to depression, anxiety and stress symptoms. ERA was negatively related to
      teachers' scores on depressive, anxious and stress symptoms, with predictive
      power above the main effects of role ambiguity and role conflict. An interaction
      between role ambiguity and ERA was also significant in predicting depression.
      Conclusions: Our study provides preliminary evidence suggesting the development
      of integrative models considering work-related stressors along with personal
      resources such as ERA aiming to prevent teachers' mental ill-health. Future
      studies should examine the influence of ERA on psychological symptoms using
      longitudinal designs.

PMID- 29016827
TI  - Successful implant of a leadless pacemaker with tine-based fixation next to an
      abandoned battery-depleted screw-in helix fixation leadless device.

PMID- 29016824
TI  - NLRP3 Inflammasome Contributes to Lipopolysaccharide-induced Depressive-Like
      Behaviors via Indoleamine 2,3-dioxygenase Induction.
AB  - Background: Inflammation may play a significant role in the pathogenesis of
      depression, although the molecular target for the treatment of inflammation
      mediated depressive symptoms remains to be elucidated. Recent studies have
      implicated the NLRP3 inflammasome in various psychiatric disorders, including
      depression. However, the underlying mechanism by which NLRP3 inflammasome
      activation mediates the progression of depressive-like behaviors remains poorly
      understood. Methods: We examined whether NLRP3 deficiency influenced depressive
      like behaviors and cerebral inflammation following systemic administration of
      lipopolysaccharide in mice. To further assess the contribution of the NLRP3
      inflammasome to the progression of depression, we evaluated the effects of NLRP3
      signaling on levels of indoleamine 2,3-dioxygenase. Results: Nlrp3-deficient mice
      exhibited significant attenuation of depressive-like behaviors and cerebral
      caspase-1 activation in a lipopolysaccharide-induced model of depression.
      Treatment with the antidepressant amitriptyline failed to block NLRP3-dependent
      activation of caspase-1, but inhibited lipopolysaccharide-promoted production of
      interleukin-1beta mRNA via suppressing NF-kappaB signaling in mouse mixed glial
      cultures. Interestingly, lipopolysaccharide administration produced NLRP3
      dependent increases in indoleamine 2,3-dioxygenase expression and activity of
      mouse brain. Furthermore, inflammasome-activating stimulations, but not treatment
      with the inflammasome product interleukin-1beta, triggered indoleamine 2,3
      dioxygenase mRNA induction in mixed glial cells. Conclusions: Our data indicate
      that the NLRP3 inflammasome is significantly implicated in the progression of
      systemic inflammation-induced depression. NLRP3-dependent caspase-1 activation
      produced significant increases in indoleamine 2,3-dioxygenase levels, which may
      play a significant role in lipopolysaccharide-induced depression. Collectively,
      our findings suggest that indoleamine 2,3-dioxygenase is a potential downstream
      mediator of the NLRP3 inflammasome in inflammation-mediated depressive-like
      behaviors.

PMID- 29016828
TI  - Workers' health surveillance: implementation of the Directive 89/391/EEC in
      Europe.
AB  - Background: European Union (EU) Directive 89/391 addressed occupational health
      surveillance, which recommends to provide workers with 'access to health
      surveillance at regular intervals', aiming to prevent work-related and
      occupational diseases. Aims: To investigate how EU countries adopted this
      Directive. Methods: We invited one selected representative per member state to
      complete a questionnaire. Results: All 28 EU countries implemented the Directive
      in some form. Workers' health surveillance (WHS) is available to all workers in
      15 countries, while in 12, only specific subgroups have access. In 21 countries,
      workers' participation is mandatory, and in 22, the employer covers the cost. In
      13 countries, access to WHS is not available to all workers but depends on
      exposure to specific risk factors, size of the enterprise or belonging to
      vulnerable groups. In 26 countries, the employer appoints and revokes the
      physician in charge of WHS. Twelve countries have no recent figures, reports or
      cost-benefit analyses of their WHS programmes. In 15 countries where reports
      exist, they are often in the native language. Conclusions: Coverage and quality
      of occupational health surveillance should be evaluated to facilitate learning
      from good practice and from scientific studies. We propose a serious debate in
      the EU with the aim of protecting workers more effectively, including the use of
      evidence-based WHS programmes.

PMID- 29016829
TI  - Differential reporting of work-related mental ill-health in doctors.
AB  - Background: Evidence suggests that the medical profession is reluctant to report
      mental ill-health despite its high prevalence. Aims: To compare differential
      reporting patterns in the incidence of work-related mental ill-health (WRMIH)
      affecting doctors with selected comparison occupational groups, as determined by
      surveillance by general practitioners (GPs), specialist psychiatrists and
      occupational physicians (OPs). Methods: New cases of medically reported WRMIH
      were reported prospectively between 2006 and 2009 by GPs, psychiatrists and OPs
      as part of The Health and Occupation Research (THOR) network. For GP and
      psychiatry reporting schemes, incidence rates (IRs) for doctors, nurses,
      teachers, corporate managers and protective service workers were calculated using
      information from the Labour Force Survey as the denominator. In OP surveys,
      participating reporters provided denominator information to calculate IRs for
      doctors, nurses and teachers. Results: Average annual IRs expressed per 100000
      person/years employed as reported by GPs, psychiatrists and OPs, respectively,
      were: doctors (309, 971, 430), nurses (891, 208, 670), teachers (1040, 136, 210)
      and for GPs and psychiatrists, respectively, were: protective service workers
      (1432, 721) and corporate managers (428, 90). Psychiatrists reported a higher
      incidence of WRMIH in doctors, whereas GPs reported higher incidences of WRMIH in
      other occupations (chi-squared test, P < 0.001). Conclusions: The distribution of
      the incidence of new cases reported across different schemes suggests a
      differential reporting pattern of WRMIH in doctors. The higher IR for doctors in
      psychiatrist-reported WRMIH could be due to factors such as disease severity and
      bypassing formal referral channels.

PMID- 29016830
TI  - A stepwise approach to conduit puncture for electrophysiological procedures in
      patients with Fontan circulation.
AB  - Aims: In patients with Fontan circulation, the conduit may be punctured for
      electrophysiological procedures. We evaluated the feasibility and safety of a
      stepwise approach to conduit puncture in adults who have undergone Fontan
      operation. Methods and results: We included 13 consecutive patients with lateral
      tunnel or extracardiac conduit Fontan circulation [median age (interquartile
      range), 24.0 (16.0-25.0) years; seven men] who had undergone electrophysiological
      procedures. We performed a stepwise approach to conduit puncture: 1st,
      Brockenbrough needle; 2nd, Brockenbrough needle with snare; 3rd, extra-steep
      Brockenbrough needle with/without snare; 4th radiofrequency transseptal needle
      with/without snare; 5th, wiring through the puncture; 6th, conduit dilation with
      angioplasty balloon; 7th, non-compliant or cutting balloon; and 8th, Inoue
      dilator. In 12 patients, conduit puncture was successful. In two, one, and two
      patients with a lateral tunnel made of the pericardium or right atrial wall,
      conduit puncture was performed by steps 1st, 2nd, and 4th, respectively. In one,
      three, two, and one patient with the Goretex lateral tunnel or extracardiac
      conduit, conduit puncture was performed by steps 1st, 6th, 7th, and 8th,
      respectively. Puncture time was significantly longer in patients with Goretex
      conduits than with pericardial conduits [62.0 (50.0-120.0) and 11.5 (10.0-14.8)
      min, respectively; P < 0.001]. A snare was necessary in patients with angles <=
      35 degrees  between the conduit wall and vertical line. Conclusion: A stepwise
      conduit puncture approach is feasible and safe in patients with lateral tunnel
      and extracardiac conduit Fontan circulation. Goretex conduit puncture was more
      difficult than pericardial conduit puncture.

PMID- 29016831
TI  - Estimating the prevalence of diabetes mellitus and thyroid disorders using
      medication data in Flanders, Belgium.
AB  - Background: Various methods exist to estimate disease prevalences. The aim of
      this study was to determine whether dispensed, self-reported and prescribed
      medication data could be used to estimate the prevalence of diabetes mellitus and
      thyroid disorders. Second, these pharmaco-epidemiological estimates were compared
      with prevalences based on self-reported diagnoses and doctor-registered
      diagnoses. Methods: Data on medication for diabetes and thyroid disorders were
      obtained from three different sources in Flanders (Belgium) for 2008: a purely
      administrative database containing data on dispensed medication, the Belgian
      National Health Interview Survey for self-reported medication and diagnoses, and
      a patient record database for prescribed medication and doctor-registered
      diagnoses. Prevalences were estimated based on medication data and compared with
      each other. Cross-tabulations of dispensed medication and self-reported
      diagnoses, and prescribed medication and doctor-registered diagnoses, were
      investigated. Results: Prevalences based on dispensed medication were the highest
      (4.39 and 2.98% for diabetes and thyroid disorders, respectively). The lowest
      prevalences were found using prescribed medication (2.39 and 1.72%,
      respectively). Cross-tabulating dispensed medication and self-reported diagnoses
      yielded a moderate to high sensitivity for diabetes (90.4%) and thyroid disorders
      (77.5%), while prescribed medication showed a low sensitivity for doctor
      registered diagnoses (56.5 and 43.6%, respectively). The specificity remained
      above 99% in all cases. Conclusions: This study was the first to perform cross
      tabulations for disease prevalence estimates between different databases and
      within (sub)populations. Purely administrative database was shown to be a
      reliable source to estimate disease prevalence based on dispensed medication.
      Prevalence estimates based on prescribed or self-reported medication were shown
      to have important limitations.

PMID- 29016834
TI  - The effect of ventricular pre-excitation on ventricular wall motion and left
      ventricular systolic function.
AB  - Aims: The relationship between ventricular pre-excitation and left ventricular
      dysfunction has been described in the absence of sustained supraventricular
      tachycardia in a series of case reports. There have been no systematic studies
      about the effect of ventricular pre-excitation with different accessory pathway
      locations on ventricular wall motion and left ventricular (LV) systolic function.
      Methods and results : Thirty patients were selected for each of 4 groups,
      including those with right septal pathways (Group 1), right free-wall pathways
      (Group 2), left free-wall pathways (Group 3), and non-pre-excited patients
      undergoing electrophysiological evaluation for supraventricular tachycardia. We
      analysed the influence of the location of the accessory pathway on ventricular
      wall motion, systolic function, ventricular synchronism, and LV size. Right-sided
      accessory pathways were associated with abnormal motion of the interventricular
      septum, LV dyssynchrony, decreased LV systolic function, and increased LV
      diameter. Eighteen of 60 cases (30.0%) with right-sided accessory pathways had LV
      dyssynchrony, and these patients had lower LV ejection fraction and higher LV end
      diastolic diameter. Conclusion : Right-sided accessory pathways may impair
      ventricular wall motion and LV systolic function, resulting in decreased LV
      ejection fraction and increased LV end-diastolic diameter. These effects occurred
      in patients with LV dyssynchrony. These effects, including LV dyssynchrony,
      resolved after radiofrequency ablation. A right-sided free-wall accessory pathway
      may have more detrimental effects than a septal accessory pathway. Left
      ventricular dyssynchrony and abnormal interventricular septal motion appeared to
      be responsible for the pathogenesis of LV dysfunction and remodelling.

PMID- 29016835
TI  - Quality of life is not improved after mitral valve surgery combined with
      epicardial left atrial cryoablation as compared with mitral valve surgery alone:
      a substudy of the double blind randomized SWEDish Multicentre Atrial Fibrillation
      study (SWEDMAF).
AB  - Aims: Concomitant surgical ablation of atrial fibrillation (AF) in patients
      undergoing mitral valve surgery (MVS) has almost become routine despite lack of
      convincing information about improved quality-of-life (QOL) and clinical benefit.
      Quality-of-life was therefore assessed after MVS with or without epicardial left
      atrial cryoablation. Methods and results: Sixty-five patients with permanent AF
      randomized to MVS with or without left atrial cryoablation, in the double-blinded
      multicentre SWEDMAF trial, replied to the Short Form 36 QOL survey at 6 and 12
      months follow-up. The QOL scores at 12 month follow-up did not differ
      significantly between patients undergoing MVS combined with cryoablation vs.
      those undergoing MVS alone regarding Physical Component Summary mean 42.8 (95%
      confidence interval 38.3-47.3) vs. mean 44.0 (40.1-47.7), P = 0.700 or Mental
      Component Summary mean 53.1 (49.7-56.4) vs. mean 48.4 (44.6-52.2), P = 0.075. All
      patients, irrespective of allocated procedure, reached the same QOL after surgery
      as an age-matched Swedish general population. The Physical Component Summary in
      patients with sinus rhythm did also not differ from those in AF at 12 months;
      mean 45.4 (42.0-48.7) vs. mean 40.5 (35.5-45.6), P = 0.096) nor was there a
      difference in Mental Component Summary; mean 51.0 (48.0-54.1) vs. mean 49.6 (44.6
      54.5), P = 0.581). Conclusion: Left atrial cryoablation added to MVS does not
      improve health-related QOL in patients with permanent AF, a finding that raises
      concerns regarding recommendations made for this combined procedure.

PMID- 29016833
TI  - The impact of surgery in molecularly defined low-grade glioma: an integrated
      clinical, radiological, and molecular analysis.
AB  - Background: Extensive resections in low-grade glioma (LGG) are associated with
      improved overall survival (OS). However, World Health Organization (WHO)
      classification of gliomas has been completely revised and is now predominantly
      based on molecular criteria. This requires reevaluation of the impact of surgery
      in molecularly defined LGG subtypes. Methods: We included 228 adults who
      underwent surgery since 2003 for a supratentorial LGG. Pre- and postoperative
      tumor volumes were assessed with semiautomatic software on T2-weighted images.
      Targeted next-generation sequencing was used to classify samples according to
      current WHO classification. Impact of postoperative volume on OS, corrected for
      molecular profile, was assessed using a Cox proportional hazards model. Results:
      Median follow-up was 5.79 years. In 39 (17.1%) histopathologically classified
      gliomas, the subtype was revised after molecular analysis. Complete resection was
      achieved in 35 patients (15.4%), and in 54 patients (23.7%) only small residue
      (0.1-5.0 cm3) remained. In multivariable analysis, postoperative volume was
      associated with OS, with a hazard ratio of 1.01 (95% CI: 1.002-1.02; P = 0.016)
      per cm3 increase in volume. The impact of postoperative volume was particularly
      strong in isocitrate dehydrogenase (IDH) mutated astrocytoma patients, where even
      very small postoperative volumes (0.1-5.0 cm) already negatively affected OS.
      Conclusion: Our data provide the necessary reevaluation of the impact of surgery
      in molecularly defined LGG and support maximal resection as first-line treatment
      for molecularly defined LGG. Importantly, in IDH mutated astrocytoma, even small
      postoperative volumes have negative impact on OS, which argues for a second-look
      operation in this subtype to remove minor residues if safely possible.

PMID- 29016836
TI  - Putting "multiforme" back into glioblastoma: intratumoral transcriptome
      heterogeneity is a consequence of its complex morphology.

PMID- 29016837
TI  - Multicenter pilot study of radiochemotherapy as first-line treatment for adults
      with medulloblastoma (NOA-07).
AB  - Background: Medulloblastoma in adult patients is rare, with 0.6 cases per
      million. Prognosis depends on clinical factors and medulloblastoma entity. No
      prospective data on the feasibility of radiochemotherapy exist. The German Neuro
      Oncology Working Group (NOA) performed a prospective descriptive multicenter
      single-arm phase II trial to evaluate feasibility and toxicity of radio
      polychemotherapy. Methods: The NOA-07 trial combined craniospinal irradiation
      with vincristine, followed by 8 cycles of cisplatin, lomustine, and vincristine.
      Adverse events, imaging and progression patterns, histological and genetic
      markers, health-related quality of life (HRQoL), and cognition were evaluated.
      Primary endpoint was the rate of toxicity-related treatment terminations after 4
      chemotherapy cycles, and the toxicity profile. The feasibility goal was reached
      if at least 45% of patients received at least 4 cycles of maintenance
      chemotherapy. Results: Thirty patients were evaluable. Each 50% showed classic
      and desmoplastic/nodular histology. Sixty-seven percent were classified into the
      sonic hedgehog (SHH) subgroup without TP53 alterations, 13% in wingless (WNT),
      and 17% in non-WNT/non-SHH. Four cycles of chemotherapy were feasible in the
      majority (n = 21; 70.0%). Hematological side effects and polyneuropathy were
      prevalent toxicities. During the active treatment period, HRQoL and verbal
      fluency improved significantly. The 3-year event-free survival rate was 66.6% at
      the time of databank lock. Conclusions: Radio-polychemotherapy did lead to
      considerable toxicity and a high amount of dose reductions throughout the first 4
      chemotherapy cycles that may affect efficacy. Thus, we propose frequent patient
      surveillance using this regimen. Modifications of the regimen may increase
      feasibility of radio-polychemotherapy of adult patients with medulloblastoma.

PMID- 29016838
TI  - The HAND1 frameshift A126FS mutation does not cause hypoplastic left heart
      syndrome in mice.
AB  - Aims: To test if a human Hand1 frame shift mutation identified in human samples
      is causative of hypoplastic left heart syndrome (HLHS). Methods and results: HLHS
      is a poorly understood single ventricle congenital heart defect that affects two
      to three infants in every 10 000 live births. The aetiologies of HLHS are largely
      unknown. The basic helix-loop-helix transcription factor HAND1 is required for
      normal heart development. Interrogation of HAND1 sequence from fixed HLHS tissues
      identified a somatic frame-shift mutation at Alanine 126 (NP_004812.1
      p.Ala126Profs13X defined as Hand1A126fs). Hand1A126fs creates a truncated HAND1
      protein that predictively functions as dominant negative. To determine if this
      mutation is causative of HLHS, we engineered a conditional Hand1A126fs mouse
      allele. Activation of this allele with Nkx2.5Cre results in E14.5 lethality
      accompanied by cardiac outflow tract and intraventricular septum abnormalities.
      Using alphaMHC-Cre or Mef2CAHF-Cre to activate Hand1A126fs results in reduced
      phenotype and limited viability. Left ventricles of Hand1A126FS mutant mice are
      not hypoplastic. Conclusions: Somatically acquired Hand1A126FS mutation is not
      causative of HLHS. Hand1A126FS mutation does exhibit embryonic lethal cardiac
      defects that reflect a dominant negative function supporting the critical role of
      Hand1 in cardiogenesis.

PMID- 29016839
TI  - Prognostic relevance of genetic alterations in diffuse lower-grade gliomas.
AB  - Background: Diffuse lower-grade gliomas (LGGs) are genetically classified into 3
      distinct subtypes based on isocitrate dehydrogenase (IDH) mutation status and
      codeletion of chromosome 1p and 19q (1p/19q). However, the subtype-specific
      effects of additional genetic lesions on survival are largely unknown. Methods:
      Using Cox proportional hazards regression modeling, we investigated the subtype
      specific effects of genetic alterations and clinicopathological factors on
      survival in each LGG subtype, in a Japanese cohort of LGG cases fully genotyped
      for driver mutations and copy number variations associated with LGGs (n = 308).
      The results were validated using a dataset from 414 LGG cases available from The
      Cancer Genome Atlas (TCGA). Results: In Oligodendroglioma, IDH-mutant and 1p/19q
      codeleted, NOTCH1 mutations (P = 0.0041) and incomplete resection (P = 0.0019)
      were significantly associated with shorter survival. In Astrocytoma, IDH-mutant,
      PIK3R1 mutations (P = 0.0014) and altered retinoblastoma pathway genes (RB1,
      CDKN2A, and CDK4) (P = 0.013) were independent predictors of poor survival. In
      IDH-wildtype LGGs, co-occurrence of 7p gain, 10q loss, mutation in the TERT
      promoter (P = 0.024), and grade III histology (P < 0.0001) independently
      predicted poor survival. IDH-wildtype LGGs without any of these factors were
      diagnosed at a younger age (P = 0.042), and were less likely to have genetic
      lesions characteristic of glioblastoma, in comparison with other IDH-wildtype
      LGGs, suggesting that they likely represented biologically different subtypes.
      These results were largely confirmed in the cohort of TCGA. Conclusions: Subtype
      specific genetic lesions can be used to stratify patients within each LGG
      subtype. enabling better prognostication and management.

PMID- 29016842
TI  - Comparison of EMG activity and blood flow during graded exertion in the
      orbicularis oris muscle of adult subjects with and without lip incompetence: a
      cross-sectional survey.
AB  - Background/Objectives: The peri-oral muscles-including orbicularis oris-are
      critical in maintaining equilibrium in tooth position. Lip incompetence (LI) can
      thus be a factor in malocclusion. We therefore aimed to validate a technique to
      evaluate not only muscle activity via electromyography (EMG) but also muscle
      endurance and fatigue via blood flow (BF) for LI. Subjects/Methods: Subjects were
      classified into increased muscle tension/lip incompetent (experimental) and
      normal muscle tension/lip competent (control) groups. Each subject then exerted
      force on a custom-made traction plate connected to a tension gauge. Using laser
      speckle imaging and electromyographic measurements, we characterized muscle
      activity and corresponding BF rates in these subjects in various states of
      resting, loading, and recovery. Results: Results showed a significant difference
      between the experimental and control groups, notably in the rate of change in BF
      to the inferior orbicularis oris muscle under conditions of increasing load
      (graded exertion). Furthermore, the data suggested that the muscles in the
      control group undergo a more prolonged (and therefore presumably more complete)
      recovery than muscles in the experimental group. These factors of reduced BF and
      short recovery may combine to accelerate muscle fatigue and produce LI.
      Limitations: The sample used here was controlled for malocclusion (including open
      bite) to eliminate this type of confounding effect. Conclusions/Implications:
      From these findings, we conclude that reduced BF and inadequate recovery in the
      orbicularis oris muscles may be more significant than EMG activity in the
      assessment of LI.

PMID- 29016843
TI  - Mesenchymal stem cells as natural biofactories for exosomes carrying miR-124a in
      the treatment of gliomas.
AB  - Background: MicroRNAs (miRs) are promising new therapeutics for glioblastoma.
      However, which miRs are most effective against glioblastomas and how these miRs
      should be delivered are major unanswered problems. Methods: To identify potent
      antiglioma miRs, we selected 8 miRs based on a literature search and screened
      them against a panel of glioma stem cell (GSC) lines, representing all of the
      glioblastoma subtypes defined by The Cancer Genome Atlas. To address delivery, we
      tested the hypothesis that ex vivo cultured bone marrow-derived mesenchymal stem
      cells (MSCs) can package miRs into exosomes and that these engineered exosomes
      can systemically deliver antiglioma miRs to glioblastomas. Results: Of the
      screened miRs, we identified miR-124a as the most effective antiglioma agent
      against GSCs. We then transduced MSCs with lentivirus vectors containing miR-124a
      and isolated vesicles from the medium. Electron microscopy, western blotting, and
      Nanosight proved that the isolated vesicles were exosomes. Quantitative PCR
      documented that these exosomes contained high levels of miR-124a, which was not
      present in control exosomes. In vitro treatment of GSCs with exosomes containing
      miR-124a (Exo-miR124) resulted in a significant reduction in viability and
      clonogenicity of GSCs compared with controls. In vivo treatment of mice harboring
      intracranial GSC267 with systemically delivered Exo-miR124 resulted in 50% of
      animals living long term. No evidence of tumor was present on histological
      analysis of the survivors. Mechanistic studies showed that miR-124a acts by
      silencing Forkhead box (FOX)A2, resulting in aberrant intracellular lipid
      accumulation. Conclusion: MSCs can be used as natural biofactories to produce Exo
      miR124, which is an effective antiglioma agent worthy of further clinical
      evaluation.

PMID- 29016844
TI  - PIK3CB/p110beta is a selective survival factor for glioblastoma.
AB  - Background: Glioblastoma (GBM) is difficult to treat. Phosphoinositide 3-kinase
      (PI3K) is an attractive therapeutic target for GBM; however, targeting this
      pathway to effectively treat GBM is not successful because the roles of PI3K
      isoforms remain to be defined. The aim of this study is to determine whether
      PIK3CB/p110beta, but not other PI3K isoforms, is a biomarker for GBM recurrence
      and important for cell survival. Methods: Gene expression and clinical relevance
      of PI3K genes in GBM patients were analyzed using online databases.
      Expression/activity of PI3K isoforms was determined using immunoblotting. PI3K
      genes were inhibited using short hairpin RNAs or isoform-selective inhibitors.
      Cell viability/growth was assessed by the MTS assay and trypan blue exclusion
      assay. Apoptosis was monitored using the caspase activity assay. Mouse GBM
      xenograft models were used to gauge drug efficacy. Results: PIK3CB/p110beta was
      the only PI3K catalytic isoform that significantly correlated with high incidence
      rate, risk, and poor survival of recurrent GBM. PIK3CA/p110alpha,
      PIK3CB/p110beta, and PIK3CD/p110delta were differentially expressed in GBM cell
      lines and primary tumor cells derived from patient specimens, whereas
      PIK3CG/p110gamma was barely detected. PIK3CB/p110beta protein levels presented a
      stronger association with the activities of PI3K signaling than other PI3K
      isoforms. Blocking p110beta deactivated PI3K signaling, whereas inhibition of
      other PI3K isoforms had no effect. Specific inhibitors of PIK3CB/p110beta, but
      not other PI3K isoforms, remarkably suppressed viability and growth of GBM cells
      and xenograft tumors in mice, with minimal cytotoxic effects on astrocytes.
      Conclusions: PIK3CB/p110beta is a biomarker for GBM recurrence and selectively
      important for GBM cell survival.

PMID- 29016846
TI  - Impact of Empathy in the Patient-Doctor Relationship on Chronic Pain Relief and
      Quality of Life: A Prospective Study in Spanish Pain Clinics.
AB  - Objective: To assess the impact of the empathy of physicians, perceived by
      patients with chronic pain, regarding pain relief and health-related quality of
      life (HR-QoL). Methods: A prospective noninterventional study was conducted in
      2,898 patients with moderate to severe chronic pain who were referred to pain
      clinics. The same physician visited each patient at baseline and after one and
      three months. Study questionnaires included the Jefferson Scale of Patient
      Perceptions of Physician Empathy (JSPPPE), the Life Orientation Test-Revised (LOT
      R), the Pain Coping Questionnaire (CAD-R), the Brief Pain Inventory Short Form
      (BPI-SF), and the EuroQol-5D (EQ-5D). Regression analyses were used to evaluate
      the independent contribution of the changes in perceived empathy over pain
      intensity and improvement of HR-QoL. Results: BPI-SF scores for pain intensity,
      rated as worst, least, average, and current pain, decreased significantly (P <
      0.001) from baseline to month 3, with reductions of 33.7%, 42.5%, 40.0%, and
      46.9%, respectively. Pain intensity decreased from 6.3 +/- 1.5 at baseline to 4.7
      +/- 1.8 at one month and 3.8 +/- 1.9 at three months (P < 0.050). Significant (P
      < 0.001) improvements in the EQ-5D tariff (+37.1%) and EQ-5D VAS (+26.7%) were
      also recorded. In the linear regression analysis, JSPPPE and LOT-R, but not CAD
      R, were significantly associated with pain relief and HR-QoL. Conclusions:
      Physicians' empathy and patients' dispositional optimism have a role in
      determining positive outcomes in patients with chronic pain. Physicians' empathy
      may therefore be a suitable, yet relatively unexplored, target for intervention.

PMID- 29016845
TI  - Pediatric low-grade gliomas: next biologically driven steps.
AB  - Despite the fact that they are not typically life-threatening, low-grade gliomas
      (LGGs) remain a significant clinical challenge in pediatric neuro-oncology due to
      comorbidities associated with these tumors and/or their treatments, and their
      propensity to multiply recurs. LGGs, in total the most common brain tumors
      arising in childhood, can often become a chronic problem requiring decades of
      management. The Second International Consensus Conference on Pediatric Low-Grade
      Gliomas held in Padua, Italy in 2016 was convened in an attempt to advance the
      pace of translating biological discoveries on LGGs into meaningful clinical
      benefit. Topics discussed included: the implications of our growing biological
      understanding of the genomics underlying these tumors; the assessment of the
      model systems available; the implications of the molecular and histopathologic
      differences between adult and pediatric diffuse gliomas; and steps needed to
      expedite targeted therapy into late-stage clinical trials for newly diagnosed
      cases. Methods for the diagnostic assessment of alterations in the Ras/mitogen
      activated protein kinase pathway, typical for these tumors, were also considered.
      While the overall tone was positive, with a consensus that progress is being and
      will continue to be made, the scale of the challenge presented by this complex
      group of tumors was also acknowledged. The conclusions and recommendations of the
      meeting panel are provided here as an outline of current thinking and a basis for
      further discussion.

PMID- 29016849
TI  - Differential protective effects of connective tissue growth factor against Abeta
      neurotoxicity on neurons and glia.
AB  - Impaired clearance of amyloid-beta peptide (Abeta) leads to abnormal
      extracellular accumulation of this neurotoxic protein that drives
      neurodegeneration in sporadic Alzheimer's disease (AD). Connective tissue growth
      factor (CTGF/CCN2) expression is elevated in plaque-surrounding astrocytes in AD
      patients. However, the role of CTGF in AD pathogenesis remains unclear. Here we
      characterized the neuroprotective activity of CTGF. We found that CTGF
      facilitated Abeta uptake and subsequent degradation within primary glia and
      neuroblastoma cells. CTGF enhanced extracellular Abeta degradation via membrane
      bound matrix metalloproteinase-14 (MMP14) in glia and extracellular MMP13 in
      neurons. In the brain of a Drosophila AD model, glial-expression of CTGF reduced
      Abeta deposits, improved locomotor function, and rescued memory deficits.
      Neuroprotective potential of CTGF against Abeta42-induced photoreceptor
      degeneration was disrupted through silencing MMPs. Therefore, CTGF may represent
      a node for potential AD therapeutics as it intervenes in glia-neuron
      communication via specific MMPs to alleviate Abeta neurotoxicity in the central
      nervous system.

PMID- 29016847
TI  - A point mutation in the ion conduction pore of AMPA receptor GRIA3 causes
      dramatically perturbed sleep patterns as well as intellectual disability.
AB  - The discovery of genetic variants influencing sleep patterns can shed light on
      the physiological processes underlying sleep. As part of a large clinical
      sequencing project, WGS500, we sequenced a family in which the two male children
      had severe developmental delay and a dramatically disturbed sleep-wake cycle,
      with very long wake and sleep durations, reaching up to 106-h awake and 48-h
      asleep. The most likely causal variant identified was a novel missense variant in
      the X-linked GRIA3 gene, which has been implicated in intellectual disability.
      GRIA3 encodes GluA3, a subunit of AMPA-type ionotropic glutamate receptors
      (AMPARs). The mutation (A653T) falls within the highly conserved transmembrane
      domain of the ion channel gate, immediately adjacent to the analogous residue in
      the Grid2 (glutamate receptor) gene, which is mutated in the mouse
      neurobehavioral mutant, Lurcher. In vitro, the GRIA3(A653T) mutation stabilizes
      the channel in a closed conformation, in contrast to Lurcher. We introduced the
      orthologous mutation into a mouse strain by CRISPR-Cas9 mutagenesis and found
      that hemizygous mutants displayed significant differences in the structure of
      their activity and sleep compared to wild-type littermates. Typically, mice are
      polyphasic, exhibiting multiple sleep bouts of sleep several minutes long within
      a 24-h period. The Gria3A653T mouse showed significantly fewer brief bouts of
      activity and sleep than the wild-types. Furthermore, Gria3A653T mice showed
      enhanced period lengthening under constant light compared to wild-type mice,
      suggesting an increased sensitivity to light. Our results suggest a role for
      GluA3 channel activity in the regulation of sleep behavior in both mice and
      humans.

PMID- 29016850
TI  - Mice lacking cyclin-dependent kinase-like 5 manifest autistic and ADHD-like
      behaviors.
AB  - Neurodevelopmental disorders frequently share common clinical features and appear
      high rate of comorbidity, such as those present in patients with attention
      deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). While
      characterizing behavioral phenotypes in the mouse model of cyclin-dependent
      kinase-like 5 (CDKL5) disorder, a neurodevelopmental disorder caused by mutations
      in the X-linked gene encoding CDKL5, we found that these mice manifested
      behavioral phenotypes mimicking multiple key features of ASD, such as impaired
      social interaction and communication, as well as increased stereotypic digging
      behaviors. These mice also displayed hyper-locomotion, increased aggressiveness
      and impulsivity, plus deficits in motor and associative learning, resembling
      primary symptoms of ADHD. Through brain region-specific biochemical analysis, we
      uncovered that loss of CDKL5 disrupts dopamine synthesis and the expression of
      social communication-related key genes, such as forkhead-box P2 and mu-opioid
      receptor, in the corticostriatal circuit. Together, our findings support that
      CDKL5 plays a role in the comorbid features of autism and ADHD, and mice lacking
      CDKL5 may serve as an animal model to study the molecular and circuit mechanisms
      underlying autism-ADHD comorbidity.

PMID- 29016848
TI  - Mdm2 mediates FMRP- and Gp1 mGluR-dependent protein translation and neural
      network activity.
AB  - Activating Group 1 (Gp1) metabotropic glutamate receptors (mGluRs), including
      mGluR1 and mGluR5, elicits translation-dependent neural plasticity mechanisms
      that are crucial to animal behavior and circuit development. Dysregulated Gp1
      mGluR signaling has been observed in numerous neurological and psychiatric
      disorders. However, the molecular pathways underlying Gp1 mGluR-dependent
      plasticity mechanisms are complex and have been elusive. In this study, we
      identified a novel mechanism through which Gp1 mGluR mediates protein translation
      and neural plasticity. Using a multi-electrode array (MEA) recording system, we
      showed that activating Gp1 mGluR elevates neural network activity, as
      demonstrated by increased spontaneous spike frequency and burst activity.
      Importantly, we validated that elevating neural network activity requires protein
      translation and is dependent on fragile X mental retardation protein (FMRP), the
      protein that is deficient in the most common inherited form of mental retardation
      and autism, fragile X syndrome (FXS). In an effort to determine the mechanism by
      which FMRP mediates protein translation and neural network activity, we
      demonstrated that a ubiquitin E3 ligase, murine double minute-2 (Mdm2), is
      required for Gp1 mGluR-induced translation and neural network activity. Our data
      showed that Mdm2 acts as a translation suppressor, and FMRP is required for its
      ubiquitination and down-regulation upon Gp1 mGluR activation. These data revealed
      a novel mechanism by which Gp1 mGluR and FMRP mediate protein translation and
      neural network activity, potentially through de-repressing Mdm2. Our results also
      introduce an alternative way for understanding altered protein translation and
      brain circuit excitability associated with Gp1 mGluR in neurological diseases
      such as FXS.

PMID- 29016851
TI  - Mutations causing acrodysostosis-2 facilitate activation of phosphodiesterase
      4D3.
AB  - Type 2 acrodysostosis (ACRDYS2), a rare developmental skeletal dysplasia
      characterized by short stature, severe brachydactyly and facial dysostosis, is
      caused by mutations in the phosphodiesterase (PDE) 4D (PDE4D) gene. Several
      arguments suggest that the mutations should result in inappropriately increased
      PDE4D activity, however, no direct evidence supporting this hypothesis has been
      presented, and the functional consequences of the mutations remain unclear. We
      evaluated the impact of four different PDE4D mutations causing ACRDYS2 located in
      different functional domains on the activity of PDE4D3 expressed in Chinese
      hamster ovary cells. Three independent approaches were used: the direct
      measurement of PDE activity in cell lysates, the evaluation of intracellular cAMP
      levels using an EPAC-based (exchange factor directly activated by cAMP)
      bioluminescence resonance energy transfer sensor , and the assessment of PDE4D3
      activation based on electrophoretic mobility. Our findings indicate that PDE4D3s
      carrying the ACRDYS2 mutations are more easily activated by protein kinase A
      induced phosphorylation than WT PDE4D3. This occurs over a wide range of
      intracellular cAMP concentrations, including basal conditions, and result in
      increased hydrolytic activity. Our results provide new information concerning the
      mechanism whereby the mutations identified in the ACRDYS2 dysregulate PDE4D
      activity, and give insights into rare diseases involving the cAMP signaling
      pathway. These findings may offer new perspectives into the selection of specific
      PDE inhibitors and possible therapeutic intervention for these patients.

PMID- 29016853
TI  - Metalloprotease-mediated cleavage of PlexinD1 and its sequestration to actin rods
      in the motoneuron disease spinal muscular atrophy (SMA).
AB  - Cytoskeletal rearrangement during axon growth is mediated by guidance receptors
      and their ligands which act either as repellent, attractant or both. Regulation
      of the actin cytoskeleton is disturbed in Spinal Muscular Atrophy (SMA), a
      devastating neurodegenerative disease affecting mainly motoneurons, but receptor
      ligand interactions leading to the dysregulation causing SMA are poorly
      understood. In this study, we analysed the role of the guidance receptor PlexinD1
      in SMA pathogenesis. We showed that PlexinD1 is cleaved by metalloproteases in
      SMA and that this cleavage switches its function from an attractant to repellent.
      Moreover, we found that the PlexinD1 cleavage product binds to actin rods,
      pathological aggregate-like structures which had so far been described for age
      related neurodegenerative diseases. Our data suggest a novel disease mechanism
      for SMA involving formation of actin rods as a molecular sink for a cleaved
      PlexinD1 fragment leading to dysregulation of receptor signaling.

PMID- 29016852
TI  - Potassium channel dysfunction underlies Purkinje neuron spiking abnormalities in
      spinocerebellar ataxia type 2.
AB  - Alterations in Purkinje neuron firing often accompany ataxia, but the molecular
      basis for these changes is poorly understood. In a mouse model of spinocerebellar
      ataxia type 2 (SCA2), a progressive reduction in Purkinje neuron firing frequency
      accompanies cell atrophy. We investigated the basis for altered Purkinje neuron
      firing in SCA2. A reduction in the expression of large-conductance calcium
      activated potassium (BK) channels and Kv3.3 voltage-gated potassium channels
      accompanies the inability of Purkinje neurons early in disease to maintain
      repetitive spiking. In association with prominent Purkinje neuron atrophy,
      repetitive spiking is restored, although at a greatly reduced firing frequency.
      In spite of a continued impairment in spike repolarization and a persistently
      reduced BK channel mediated afterhyperpolarization (AHP), repetitive spiking is
      maintained, through the increased activity of barium-sensitive potassium
      channels, most consistent with inwardly rectifying potassium (Kir) channels.
      Increased activity of Kir channels results in the generation of a novel AHP not
      seen in wild-type Purkinje neurons that also accounts for the reduced firing
      frequency late in disease. Homeostatic changes in Purkinje neuron morphology that
      help to preserve repetitive spiking can also therefore have deleterious
      consequences for spike frequency. These results suggest that the basis for
      spiking abnormalities in SCA2 differ depending on disease stage, and
      interventions targeted towards correcting potassium channel dysfunction in ataxia
      need to be tailored to the specific stage in the degenerative process.

PMID- 29016854
TI  - Absence of RNase H2 triggers generation of immunogenic micronuclei removed by
      autophagy.
AB  - Hypomorphic mutations in the DNA repair enzyme RNase H2 cause the
      neuroinflammatory autoimmune disorder Aicardi-Goutieres syndrome (AGS).
      Endogenous nucleic acids are believed to accumulate in patient cells and
      instigate pathogenic type I interferon expression. However, the underlying
      nucleic acid species amassing in the absence of RNase H2 has not been established
      yet. Here, we report that murine RNase H2 knockout cells accumulated cytosolic
      DNA aggregates virtually indistinguishable from micronuclei. RNase H2-dependent
      micronuclei were surrounded by nuclear lamina and most of them contained damaged
      DNA. Importantly, they induced expression of interferon-stimulated genes (ISGs)
      and co-localized with the nucleic acid sensor cGAS. Moreover, micronuclei
      associated with RNase H2 deficiency were cleared by autophagy. Consequently,
      induction of autophagy by pharmacological mTOR inhibition resulted in a
      significant reduction of cytosolic DNA and the accompanied interferon signature.
      Autophagy induction might therefore represent a viable therapeutic option for
      RNase H2-dependent disease. Endogenous retroelements have previously been
      proposed as a source of self-nucleic acids triggering inappropriate activation of
      the immune system in AGS. We used human RNase H2-knockout cells generated by
      CRISPR/Cas9 to investigate the impact of RNase H2 on retroelement propagation.
      Surprisingly, replication of LINE-1 and Alu elements was blunted in cells lacking
      RNase H2, establishing RNase H2 as essential host factor for the mobilisation of
      endogenous retrotransposons.

PMID- 29016855
TI  - Enhanced tau pathology via RanBP9 and Hsp90/Hsc70 chaperone complexes.
AB  - Accumulation of amyloid beta (Abeta) and tau represent the two major pathological
      hallmarks of Alzheimer's disease (AD). Despite the critical importance of Abeta
      accumulation as an early event in AD pathogenesis, multiple lines of evidence
      indicate that tau is required to mediate Abeta-induced neurotoxic signals in
      neurons. We have previously shown that the scaffolding protein Ran-binding
      protein 9 (RanBP9), which is highly elevated in brains of AD and AD mouse models,
      both enhances Abeta production and mediates Abeta-induced neurotoxicity. However,
      it is unknown whether and how RanBP9 transmits Abeta-induced neurotoxic signals
      to tau. Here we show for the first time that overexpression or knockdown of
      RanBP9 directly enhances and reduces tau levels, respectively, in vitro and in
      vivo. Such changes in tau levels are associated with the ability of RanBP9 to
      physically interact with tau and heat shock protein 90/heat shock cognate 70
      (Hsp90/Hsc70) complexes. Meanwhile, both RanBP9 and tau levels are simultaneously
      reduced by Hsp90 or Hsc70 inhibitors, whereas overexpression or knockdown of
      RanBP9 significantly diminishes the anti-tau potency of Hsp90/Hsc70 inhibitors as
      well as Hsc70 variants (WT & E175S). Further, RanBP9 increases the capacity for
      Hsp90 and Hsc70 complexes to bind ATP and enhances their ATPase activities in
      vitro. These observations in vitro and cell lines are recapitulated in primary
      neurons and in vivo, as genetic reduction in RanBP9 not only ameliorates
      tauopathy in Tau-P301S mice but also rescues the deficits in synaptic integrity
      and plasticity.

PMID- 29016857
TI  - Biallelic mutation of UNC50, encoding a protein involved in AChR trafficking, is
      responsible for arthrogryposis.
AB  - Arthrogryposis multiplex congenita (AMC) is a developmental condition
      characterized by multiple joint contractures resulting from reduced or absent
      fetal movements. Homozygosity mapping of disease loci combined with whole exome
      sequencing in a consanguineous family presenting with lethal AMC allowed the
      identification of a homozygous frameshift deletion in UNC50 gene
      (c.750_751del:p.Cys251Phefs*4) in the index case. To assess the effect of the
      mutation, an equivalent mutation in the Caenorhabditis elegans orthologous gene
      was created using CRISPR/Cas9. We demonstrated that unc-50(kr331) modification
      caused the loss of acetylcholine receptor (AChR) expression in C. elegans muscle.
      unc-50(kr331) animals were as resistant to the cholinergic agonist levamisole as
      unc-50 null mutants suggesting that AChRs were no longer expressed in this animal
      model. This was confirmed by using a knock-in strain in which a red fluorescent
      protein was inserted into the AChR locus: no signal was detected in unc-50(kr331)
      background, suggesting that UNC-50, a protein known to be involved in AChR
      trafficking, was no longer functional. These data indicate that biallelic
      mutation in the UNC50 gene underlies AMC through a probable loss of AChR
      expression at the neuromuscular junction which is essential for the cholinergic
      transmission during human muscle development.

PMID- 29016856
TI  - Neuronal overexpression of Ube3a isoform 2 causes behavioral impairments and
      neuroanatomical pathology relevant to 15q11.2-q13.3 duplication syndrome.
AB  - Maternally derived copy number gains of human chromosome 15q11.2-q13.3 (Dup15q
      syndrome or Dup15q) cause intellectual disability, epilepsy, developmental delay,
      hypotonia, speech impairments, and minor dysmorphic features. Dup15q syndrome is
      one of the most common and penetrant chromosomal abnormalities observed in
      individuals with autism spectrum disorder (ASD). Although ~40 genes are located
      in the 15q11.2-q13.3 region, overexpression of the ubiquitin-protein E3A ligase
      (UBE3A) gene is thought to be the predominant molecular cause of the phenotypes
      observed in Dup15q syndrome. The UBE3A gene demonstrates maternal-specific
      expression in neurons and loss of maternal UBE3A causes Angelman syndrome, a
      neurodevelopmental disorder with some overlapping neurological features to
      Dup15q. To directly test the hypothesis that overexpression of UBE3A is an
      important underlying molecular cause of neurodevelopmental dysfunction, we
      developed and characterized a mouse overexpressing Ube3a isoform 2 in excitatory
      neurons. Ube3a isoform 2 is conserved between mouse and human and known to play
      key roles in neuronal function. Transgenic mice overexpressing Ube3a isoform 2 in
      excitatory forebrain neurons exhibited increased anxiety-like behaviors, learning
      impairments, and reduced seizure thresholds. However, these transgenic mice
      displayed normal social approach, social interactions, and repetitive motor
      stereotypies that are relevant to ASD. Reduced forebrain, hippocampus, striatum,
      amygdala, and cortical volume were also observed. Altogether, these findings show
      neuronal overexpression of Ube3a isoform 2 causes phenotypes translatable to
      neurodevelopmental disorders.

PMID- 29016859
TI  - A functional variant in MIR4300HG, the host gene of microRNA MIR4300 is
      associated with progression of adolescent idiopathic scoliosis.
AB  - Adolescent idiopathic scoliosis (AIS) is a common spinal deformity affecting
      millions of children. Since treatment and prognosis of AIS depend on curve
      progression, identifying factors related to AIS curve progression is important in
      its management. Although several genetic loci for AIS occurrence are reported, no
      locus for curve progression has been identified. To identify genes associated
      with AIS progression, we conducted a genome-wide association study followed by a
      replication study using a total of 2,543 AIS subjects who were evaluated for the
      curve progression. We identified a significantly associated locus on chromosome
      11q14.1 (P = 1.98 * 10-9, odds ratio = 1.56). In silico and in vitro analyses
      identified a functional variant, rs35333564 in MIR4300HG, the host gene of a
      microRNA, MIR4300. The genomic region containing rs35333564 had enhancer
      activity, which was decreased in its risk allele. Our data suggest that decrease
      of MIR4300 is related to AIS progression.

PMID- 29016860
TI  - Primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 encodes a novel
      Rac1/Cdc42 GAP that modulates cell migration and blood-aqueous barrier function.
AB  - PLEKHA7, a gene recently associated with primary angle closure glaucoma (PACG),
      encodes an apical junctional protein expressed in components of the blood aqueous
      barrier (BAB). We found that PLEKHA7 is down-regulated in lens epithelial cells
      and in iris tissue of PACG patients. PLEKHA7 expression also correlated with the
      C risk allele of the sentinel SNP rs11024102 with the risk allele carrier groups
      having significantly reduced PLEKHA7 levels compared to non-risk allele carriers.
      Silencing of PLEKHA7 in human immortalized non-pigmented ciliary epithelium (h
      iNPCE) and primary trabecular meshwork cells, which are intimately linked to BAB
      and aqueous humor outflow respectively, affected actin cytoskeleton organization.
      PLEKHA7 specifically interacts with GTP-bound Rac1 and Cdc42, but not RhoA, and
      the activation status of the two small GTPases is linked to PLEKHA7 expression
      levels. PLEKHA7 stimulates Rac1 and Cdc42 GTP hydrolysis, without affecting
      nucleotide exchange, identifying PLEKHA7 as a novel Rac1/Cdc42 GAP. Consistent
      with the regulatory role of Rac1 and Cdc42 in maintaining the tight junction
      permeability, silencing of PLEKHA7 compromises the paracellular barrier between h
      iNPCE cells. Thus, downregulation of PLEKHA7 in PACG may affect BAB integrity and
      aqueous humor outflow via its Rac1/Cdc42 GAP activity, thereby contributing to
      disease etiology.

PMID- 29016862
TI  - Ube3a deficiency inhibits amyloid plaque formation in APPswe/PS1deltaE9 mouse
      model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by
      progressive decline in memory and cognitive function. Pathological hallmark of AD
      includes aberrant aggregation of amyloid beta (Abeta) peptide, which is produced
      upon sequential cleavage of amyloid precursor protein (APP) by beta- and gamma 
      secretases. On the contrary, alpha-secretase cleaves APP within the Abeta
      sequence and thereby prevents Abeta generation. Here, we investigated the role of
      ubiquitin ligase Ube3a (involved in synaptic function and plasticity) in the
      pathogenesis of AD using APPswe/PS1deltaE9 transgenic mouse model and first
      noticed that soluble pool of Ube3a was age-dependently decreased in AD mouse in
      comparison with wild type controls. To further explore the role of Ube3a in AD
      patho-mechanism, we generated brain Ube3a-deficient AD mice that exhibited
      accelerated cognitive and motor deficits compared with AD mice. Interestingly,
      these Ube3a-deficient AD mice were excessively obese from their age of 12 months
      and having shorter lifespan. Biochemical analysis revealed that the Ube3a
      deficient AD mice had significantly reduced level of Abeta generation and amyloid
      plaque formation in their brain compared with age-matched AD mice and this effect
      could be due to the increased activity of alpha-secretase, ADAM10 (a disintegrin
      and metalloproteinase-10) that shift the proteolysis of APP towards non
      amyloidogenic pathway. These findings suggest that aberrant function of Ube3a
      could influence the progression of AD and restoring normal level of Ube3a might
      be beneficial for AD.

PMID- 29016864
TI  - Loss of host-derived osteopontin creates a glioblastoma-promoting
      microenvironment.
AB  - Background: Microglia and periphery-derived monocytes infiltrate human and mouse
      glioblastoma and their density is positively correlated with malignancy. Using
      microarray and RNA sequencing, we have previously shown that glioblastoma
      associated microglia/monocytes (GAMs) express osteopontin/SPP1. Methods: We used
      quantitative reverse transcriptase PCR, immunofluorescence stainings, western
      blot, and flow cytometry to identify the various sources of osteopontin (OPN)
      expression in human and mouse glioblastoma. We implanted wild type GL261
      glioblastoma cells, which do not express significant levels of OPN, into wild
      type and OPN-/- mice to investigate the role of microenvironment-derived OPN on
      glioblastoma progression. Results: Our data indicate that GAMs are the
      predominant source of OPN in both human and mouse glioblastoma and express only
      the secreted form of OPN. Loss of microenvironment-derived OPN enhanced tumor
      progression. Staining by Ki67 and terminal deoxynucleotidyl transferase
      deoxyuridine triphosphate nick end labeling showed no difference in overall cell
      proliferation but a decreased apoptosis rate in tumors in OPN-/- mice. CD31
      staining showed a significantly decreased number of microvessels in tumors in OPN
      /- mice, accompanied by reduced coverage of vessels with platelet derived growth
      factor receptor beta+ pericytes. Flow cytometry analysis revealed a significant
      increase of CD11b+/CD45low microglia but not of CD11b+/CD45high
      macrophages/monocytes in tumors in OPN-/- mice. Sorted CD11b+ cells from wild
      type and OPN-/- naive brains and tumors did not show a significant difference in
      the expression pattern of activation marker genes. Conclusion: Our results show
      that in tested human and mouse glioblastoma samples, OPN is predominantly
      expressed and secreted by GAMs and that, in contrast to OPN expression in the
      tumor cells per se, loss of stroma-derived OPN creates a glioblastoma-promoting
      microenvironment.

PMID- 29016866
TI  - Anesthetic Test Dose and Seizure Risk with Cervical Transforaminal Epidural
      Steroid Injection.

PMID- 29016861
TI  - DJ-1 is a redox sensitive adapter protein for high molecular weight complexes
      involved in regulation of catecholamine homeostasis.
AB  - DJ-1 is an oxidation sensitive protein encoded by the PARK7 gene. Mutations in
      PARK7 are a rare cause of familial recessive Parkinson's disease (PD), but
      growing evidence suggests involvement of DJ-1 in idiopathic PD. The key clinical
      features of PD, rigidity and bradykinesia, result from neurotransmitter
      imbalance, particularly the catecholamines dopamine (DA) and noradrenaline. We
      report in human brain and human SH-SY5Y neuroblastoma cell lines that DJ-1
      predominantly forms high molecular weight (HMW) complexes that included RNA
      metabolism proteins hnRNPA1 and PABP1 and the glycolysis enzyme GAPDH. In cell
      culture models the oxidation status of DJ-1 determined the specific complex
      composition. RNA sequencing indicated that oxidative changes to DJ-1 were
      concomitant with changes in mRNA transcripts mainly involved in catecholamine
      metabolism. Importantly, loss of DJ-1 function upon knock down (KD) or expression
      of the PD associated form L166P resulted in the absence of HMW DJ-1 complexes. In
      the KD model, the absence of DJ-1 complexes was accompanied by impairment in
      catecholamine homeostasis, with significant increases in intracellular DA and
      noraderenaline levels. These changes in catecholamines could be rescued by re
      expression of DJ-1. This catecholamine imbalance may contribute to the particular
      vulnerability of dopaminergic and noradrenergic neurons to neurodegeneration in
      PARK7-related PD. Notably, oxidised DJ-1 was significantly decreased in
      idiopathic PD brain, suggesting altered complex function may also play a role in
      the more common sporadic form of the disease.

PMID- 29016863
TI  - A TUBB6 mutation is associated with autosomal dominant non-progressive congenital
      facial palsy, bilateral ptosis and velopharyngeal dysfunction.
AB  - Congenital cranial dysinnervation disorders (CCDDs) comprise a heterogeneous
      spectrum of diseases characterized by congenital, non-progressive impairment of
      eye, eyelid and/or facial movements including Mobius syndrome, Duane retraction
      syndrome, congenital ptosis, and congenital fibrosis of the extraocular muscles.
      Over the last 20 years, several CCDDs have been identified as neurodevelopmental
      disorders that are caused by mutations of genes involved in brain and cranial
      nerve development, e.g. KIF21A and TUBB3 that each plays a pivotal role for
      microtubule function. In a five-generation pedigree, we identified a heterozygous
      mutation of TUBB6, a gene encoding a class V tubulin which has not been linked to
      a human hereditary disease so far. The missense mutation (p.Phe394Ser) affects an
      amino acid residue highly conserved in evolution, and co-segregates with a
      phenotype characterized by congenital non-progressive bilateral facial palsy and
      congenital velopharyngeal dysfunction presenting with varying degrees of
      hypomimia, rhinophonia, impaired gag reflex and bilateral ptosis. Expression of
      the mutated protein in yeast led to an impaired viability compared to wildtype
      cells when exposed to the microtubule-poison benomyl. Our findings enlarge the
      spectrum of tubulinopathies and emphasize that mutations of TUBB6 should be
      considered in patients with congenital non-progressive facial palsy. Further
      studies are needed to verify whether this phenotype is indeed part of the CCDD
      spectrum.

PMID- 29016867
TI  - The Response of the Primary Motor Cortex to Neuromodulation is Altered in Chronic
      Low Back Pain: A Preliminary Study.
AB  - Objective: Neuromodulation is increasingly investigated for the treatment of low
      back pain (LBP). However, the neurophysiological effects of common
      neuromodulatory techniques (anodal transcranial direct current stimulation [tDCS]
      and peripheral electrical stimulation [PES]) have not been investigated in people
      with chronic LBP. Here we aimed to compare the effect of three neuromodulatory
      protocols (anodal tDCS, high intensity PES, and a priming protocol of combined
      tDCS/PES) on primary motor cortex (M1) excitability in people with and without
      chronic LBP. Design: Cross-sectional. Setting: University laboratory.
      Participants: Ten individuals with chronic LBP and 10 pain-free controls.
      Methods: Participants received four interventions in random order across separate
      sessions: 1) anodal tDCS to M1 + PES to the back muscles; 2) tDCS + sham PES; 3)
      sham tDCS + PES; or 4) sham tDCS + sham PES. Motor cortical excitability (map
      volume, discrete map peaks, and cortical silent period [CSP]) was measured before
      and after each intervention. Results: Anodal tDCS increased M1 excitability
      (increased map volume and reduced CSP) in controls but had no effect in the LBP
      group. PES reduced M1 excitability in both groups. The combined tDCS + PES
      treatment increased M1 excitability in the LBP group but had no effect in
      controls. Conclusions: The neurophysiological response to common neuromodulatory
      treatments differs between people with and without LBP. This has relevance for
      the design and tailoring of neuromodulation in pain. Further, if the goal of
      treatment is to increase M1 excitability, a priming protocol (e.g., combined tDCS
      + PES) may be more effective than tDCS alone.

PMID- 29016868
TI  - Efficacy and Safety of Lubiprostone in Patients with Opioid-Induced Constipation:
      Phase 3 Study Results and Pooled Analysis of the Effect of Concomitant Methadone
      Use on Clinical Outcomes.
AB  - Objective: The efficacy and safety of oral lubiprostone for relieving symptoms of
      opioid-induced constipation (OIC) in patients with chronic noncancer pain were
      evaluated in a randomized, double-blind, placebo-controlled study. These data
      were also pooled with those from two similar phase 3 studies to explore the
      effects of methadone on treatment response. Methods: In the primary study, adults
      with OIC (fewer than three spontaneous bowel movements [SBMs] per week) were
      randomized to receive lubiprostone 24 mcg or placebo twice daily for 12 weeks.
      The primary end point was a change from baseline in the frequency of SBMs at week
      8 in patients without a prior dose reduction. For the pooled analysis, the
      efficacy of lubiprostone was compared with placebo in patients receiving
      methadone or nonmethadone opioids. Responders were defined as patients with nine
      or more weeks of nonmissing SBM data who had one or more additional SBMs per week
      from baseline for each week that data were available and three or more SBMs per
      week for nine or more weeks. Results: In the primary study, the change from
      baseline at week 8 in SBM frequency was similar in the lubiprostone and placebo
      groups (P = 0.842). In the pooled analysis, the response rate was significantly
      higher with lubiprostone treatment vs placebo for patients receiving nonmethadone
      opioids (P = 0.002) but was similar between lubiprostone treatment and placebo in
      patients receiving methadone (P = 0.692). The safety profile of lubiprostone was
      unaffected by methadone use. Conclusions: The phase 3 study did not meet its
      primary efficacy end point. However, analysis of pooled data from all phase 3
      studies in the OIC clinical development program, stratified by methadone opioid
      usage, confirmed that lubiprostone is effective for treatment of OIC in patients
      taking nonmethadone opioids; no safety concerns were identified based on the type
      of opioid used.

PMID- 29016865
TI  - Inability of positive phase II clinical trials of investigational treatments to
      subsequently predict positive phase III clinical trials in glioblastoma.
AB  - Background: Glioblastoma is the most common primary malignant brain tumor in
      adults, but effective therapies are lacking. With the scarcity of positive phase
      III trials, which are increasing in cost, we examined the ability of positive
      phase II trials to predict statistically significant improvement in clinical
      outcomes of phase III trials. Methods: A PubMed search was conducted to identify
      phase III clinical trials performed in the past 25 years for patients with newly
      diagnosed or recurrent glioblastoma. Trials were excluded if they did not examine
      an investigational chemotherapy or agent, if they were stopped early owing to
      toxicity, if they lacked prior phase II studies, or if a prior phase II study was
      negative. Results: Seven phase III clinical trials in newly diagnosed
      glioblastoma and 4 phase III clinical trials in recurrent glioblastoma met the
      inclusion criteria. Only 1 (9%) phase III study documented an improvement in
      overall survival and changed the standard of care. Conclusion: The high failure
      rate of phase III trials demonstrates the urgent need to increase the reliability
      of phase II trials of treatments for glioblastoma. Strategies such as the use of
      adaptive trial designs, Bayesian statistics, biomarkers, volumetric imaging, and
      mathematical modeling warrant testing. Additionally, it is critical to increase
      our expectations of phase II trials so that positive findings increase the
      probability that a phase III trial will be successful.

PMID- 29016858
TI  - Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA
      methylation: findings from the pregnancy and childhood epigenetics (PACE)
      consortium.
AB  - Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at
      birth and later in life. Individual studies have shown that epigenetic
      modifications such as DNA methylation could contribute. Within the Pregnancy and
      Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between
      pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood
      DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer
      causality by comparing the effects of maternal versus paternal BMI and
      incorporating genetic variation. In four additional cohorts (1,817 mother-child
      pairs), we meta-analysed the association between maternal BMI at the start of
      pregnancy and blood methylation in adolescents. In newborns, maternal BMI was
      associated with small (<0.2% per BMI unit (1 kg/m2), P < 1.06 * 10-7) methylation
      variation at 9,044 sites throughout the genome. Adjustment for estimated cell
      proportions greatly attenuated the number of significant CpGs to 104, including
      86 sites common to the unadjusted model. At 72/86 sites, the direction of the
      association was the same in newborns and adolescents, suggesting persistence of
      signals. However, we found evidence for acausal intrauterine effect of maternal
      BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered
      analysis identified robust associations between maternal adiposity and variations
      in newborn blood DNA methylation, but these small effects may be better explained
      by genetic or lifestyle factors than a causal intrauterine mechanism. This
      highlights the need for large-scale collaborative approaches and the application
      of causal inference techniques in epigenetic epidemiology.

PMID- 29016870
TI  - Complications of pulmonary vein isolation in atrial fibrillation: predictors and
      comparison between four different ablation techniques: Results from the
      MIddelheim PVI-registry.
AB  - Aims: To define predictors of complications of pulmonary vein isolation (PVI) and
      compare safety between different ablation techniques. Methods and results: One
      thousand patients with atrial fibrillation (AF) (age 60 +/- 10, 72% males,
      CHA2DS2-VASc score 1 +/- 1) underwent PVI using various techniques: conventional
      PVI (CPVI) using mapping with irrigated point-per-point RF ablation (n = 576),
      multi-electrode RF ablation with the pulmonary vein ablation catheter (PVAC) (n =
      272) or high density mesh ablator (HDMA) (n = 59) and cryoballoon (CB) ablation
      (n = 93). A complication was defined as any procedure-related adverse event
      resulting in permanent injury or death, requiring intervention or treatment, or
      prolonging/requiring hospitalization for >48 h. A total of 105 (10.5%)
      complications occurred in 101 (10.1%) patients. No periprocedural death occurred.
      Most frequent complications were vascular complications (4%) and pericarditis
      (3.1%). Seven patients experienced permanent deficit due to PV stenosis (n = 3, 1
      CPVI, 2 PVAC) (n = 3) and phrenic nerve palsy (PNP) (n = 4, 3 CPVI, 1 PVAC).
      Independent predictors of complications were female sex [odds ratio (OR) = 1.73;
      95% confidence interval (CI) 1.08-2.79; P = 0.023], CHA2DS2-VASc score (OR =
      1.24; 95% CI 1.01-1.52; P = 0.039), and ablation technique (P = 0.006) in
      multivariable-adjusted analysis. Among the different techniques, CB (P = 0.047)
      and PVAC ablation (P = 0.003) had lowest overall complication rates. Complication
      profile (type/severity) differed between techniques (association between CB and
      PNP, CPVI and pericardial injury, PVAC and transient ischaemic attack/PV
      stenosis). Conclusion: Overall complication rate of PVI with various techniques
      is 10.5%. Permanent deficit occurred only after PVAC and CPVI in 0.7% of
      patients. Female sex and a higher CHA2DS2-VASc score increase, while PVAC and CB
      PVI decrease, overall risk. Differences in overall safety and individual
      complication profile make selection of the ablation technique in relation to
      clinical risk profile possible.

PMID- 29016869
TI  - Clinical characteristics associated with postoperative seizure control in adult
      low-grade gliomas: a systematic review and meta-analysis.
AB  - Background: Epilepsy is the most common symptom in patients with supratentorial
      low-grade gliomas (LGGs), which adversely affects the patient's quality of life.
      Poor seizure control with anti-epileptic therapy is an indication for surgery in
      these patients. Recent studies have sought to identify predictors of
      postoperative seizure control after surgical resection of LGG; gross total
      resection was shown to be a significant predictor in this respect. However, the
      prognostic value of other factors is not clear. Methods: We performed a
      systematic review and meta-analysis of 23 studies with a combined study
      population of 2641 patients with LGG, in order to identify potential factors
      associated with favorable postoperative seizure control. Data were extracted on
      age and sex of patient, tumor location, tumor histology, type of seizure, seizure
      duration, extent of resection, and imaging characteristics. Results: Patients
      >=45 years of age achieved better postoperative seizure control (risk ratio [RR],
      0.89; 95% CI, 0.81-0.99). Focal seizures were associated with poor seizure
      control (RR, 1.32; 95% CI, 1.18-1.49) compared with generalized seizures (RR,
      0.77; 95% CI, 0.68-0.87). Prolonged history of seizures (>=1 y) had a negative
      impact on postoperative seizure control (RR, 1.22; 95% CI, 1.10-1.34). Gross
      total resection was superior to subtotal resection with respect to postoperative
      seizure control (RR, 0.68; 95% CI, 0.63-0.73). Conclusions: This systematic
      review and meta-analysis identified predictors of postoperative seizure control
      in patients undergoing surgical resection of LGGs. Our results provide a
      reference for clinical treatment of LGG-related epilepsy.

PMID- 29016871
TI  - Cost-effectiveness of IDH testing in diffuse gliomas according to the 2016 WHO
      classification of tumors of the central nervous system recommendations.
AB  - Background: Due to the decreasing prevalence of IDH1 mutations in older patients,
      the 2016 World Health Organization (WHO) classification of brain tumors proposed
      not to perform sequencing for isocitrate dehydrogenase (IDH) in glioblastoma
      patients >=55 years old. We present a cost-effectiveness analysis to estimate the
      financial impact of these guidelines. Methods: From 2010 to 2015 we performed
      1023 IDH tests in gliomas, amounting to ~$1.09 million in direct laboratory test
      costs. Samples were tested using R132H-specific immunohistochemistry, DNA
      sequencing validated for detection of noncanonical IDH1/2 mutations, or both
      methods. Results: In cases tested by DNA sequencing, the fraction of non-R132H
      mutations was 5.4%, which included only 2 high-grade gliomas in patients >=55
      years (0.9%). When remodeling the optimal age cutoff in our patient population
      using 5-year age-binning, we found a 10-times higher pretest probability for the
      presence of a noncanonical IDH1 mutation in the setting of a negative IDH1-R132H
      immunohistochemistry result in patients <55 years. Applying the independently
      confirmed age cutoff of 55 years to glioblastoma patients (64%) would result in
      $403200 saved (43%). By not performing sequencing in patients >=55 years, the
      turn-around time to final integrated neuropathological diagnosis is reduced by
      53%, allowing these patients to gain earlier benefits from personalized genomic
      medicine. Conclusion: The negligible prevalence of noncanonical IDH mutations in
      glioblastoma patients >=55 years argues against universal IDH sequencing in this
      population. We predict that adoption of this age-based sequencing cutoff
      recommendation from the 2016 WHO guidelines will result in significant cost and
      time savings throughout the global health care system.

PMID- 29016841
TI  - 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and
      surgical ablation of atrial fibrillation: Executive summary.

PMID- 29016874
TI  - The Number of Active But Not Latent Trigger Points Associated with Widespread
      Pressure Pain Hypersensitivity in Women with Episodic Migraines.
AB  - Objective: Previous studies suggest that trigger points (TrPs) contribute to
      migraine pain, but no data is available on the effects of TrPs on pressure pain
      sensitivity. Our objective was to investigate the association between the number
      of TrPs and widespread pressure hypersensitivity in women with episodic
      migraines. Methods: Ninety-five women with episodic migraines participated.
      Clinical features of migraines, that is, intensity, duration, frequency, and
      onset, were collected. Active and latent TrPs were bilaterally explored in the
      temporalis, masseter, suboccipital, sternocleidomastoid, upper trapezius, and
      splenius capitis musculature. Pressure pain thresholds (PPTs) were assessed over
      the trigeminal area (i.e., temporalis muscle), extratrigeminal (i.e., C5/C6
      zygapophyseal joint), and a distant pain-free point (i.e., tibialis anterior
      muscle). Results: Active TrPs in the temporalis and upper trapezius muscles were
      the most prevalent. The number of active but not latent TrPs was significantly
      and negatively associated with PPTs: the higher the number of active TrPs, the
      lower the widespread PPT and the more generalized sensitization. Conclusions:
      This study found that the number of active but not latent TrPs in head and neck
      and shoulder muscles was associated with widespread pressure hypersensitivity in
      women with episodic migraines, suggesting a potential contribution of active TrPs
      as contributors for sensitization processes in migraines.

PMID- 29016873
TI  - Cgnl1, an endothelial junction complex protein, regulates GTPase mediated
      angiogenesis.
AB  - Aims: The formation of cell-cell and cell-extra cellular matrix (ECM) contacts by
      endothelial cells (ECs) is crucial for the stability and integrity of a vascular
      network. We previously identified cingulin-like 1 (Cgnl1) in a transcriptomic
      screen for new angiogenic modulators. Here we aim to study the function of the
      cell-cell junction associated protein Cgnl1 during vessel formation. Methods and
      results: Unlike family member cingulin, Cgnl1 expression is enriched in ECs
      during vascular growth. Cgnl1 is important for the formation of multicellular
      tubule structures, as shown in vitro using loss-of function assays in a 3D matrix
      co-culture system that uses primary human ECs and supporting mural cells. Further
      studies revealed that Cgnl1 regulates vascular growth by promoting Ve-cadherin
      association with the actin cytoskeleton, thereby stabilizing adherens junctions.
      Cgnl1 also regulates focal adhesion assembly in response to ECM contact,
      promoting vinculin and paxillin recruitment and focal adhesion kinase signalling.
      In vivo, we demonstrate in a postnatal retinal vascular development model in mice
      that Cgnl1 function is crucial for sustaining neovascular growth and stability.
      Conclusions: Our data demonstrate a functional relevance for Cgnl1 as a defining
      factor in new vessel formation both in vitro and in vivo.

PMID- 29016872
TI  - Affinity States of Striatal Dopamine D2 Receptors in Antipsychotic-Free Patients
      with Schizophrenia.
AB  - Background: Dopamine D2 receptors are reported to have high-affinity (D2High) and
      low-affinity (D2Low) states. Although an increased proportion of D2High has been
      demonstrated in animal models of schizophrenia, few clinical studies have
      investigated this alteration of D2High in schizophrenia in vivo. Methods: Eleven
      patients with schizophrenia, including 10 antipsychotic-naive and 1 antipsychotic
      free individuals, and 17 healthy controls were investigated. Psychopathology was
      assessed by Positive and Negative Syndrome Scale, and a 5-factor model was used.
      Two radioligands, [11C]raclopride and [11C]MNPA, were employed to quantify total
      dopamine D2 receptor and D2High, respectively, in the striatum by measuring their
      binding potentials. Binding potential values of [11C]raclopride and [11C]MNPA and
      the binding potential ratio of [11C]MNPA to [11C]raclopride in the striatal
      subregions were statistically compared between the 2 diagnostic groups using
      multivariate analysis of covariance controlling for age, gender, and smoking.
      Correlations between binding potential and Positive and Negative Syndrome Scale
      scores were also examined. Results: Multivariate analysis of covariance
      demonstrated a significant effect of diagnosis (schizophrenia and control) on the
      binding potential ratio (P=.018), although the effects of diagnosis on binding
      potential values obtained with either [11C]raclopride or [11C]MNPA were
      nonsignificant. Posthoc test showed that the binding potential ratio was
      significantly higher in the putamen of patients (P=.017). The Positive and
      Negative Syndrome Scale "depressed" factor in patients was positively correlated
      with binding potential values of both ligands in the caudate. Conclusions: The
      present study indicates the possibilities of: (1) a higher proportion of D2High
      in the putamen despite unaltered amounts of total dopamine D2 receptors; and (2)
      associations between depressive symptoms and amounts of caudate dopamine D2
      receptors in patients with schizophrenia.

PMID- 29016832
TI  - Contemporary stroke prevention strategies in 11 096 European patients with atrial
      fibrillation: a report from the EURObservational Research Programme on Atrial
      Fibrillation (EORP-AF) Long-Term General Registry.
AB  - Aims: Contemporary data regarding atrial fibrillation (AF) management and current
      use of oral anticoagulants (OACs) for stroke prevention are needed. Methods and
      results: The EURObservational Research Programme on AF (EORP-AF) Long-Term
      General Registry analysed consecutive AF patients presenting to cardiologists in
      250 centres from 27 European countries. From 2013 to 2016, 11 096 patients were
      enrolled (40.7% female; mean age 69 +/- 11 years). At discharge, OACs were used
      in 9379 patients (84.9%), with non-vitamin K antagonists (NOACs) accounting for
      40.9% of OACs. Antiplatelet therapy alone was used by 20% of patients, while no
      antithrombotic treatment was prescribed in 6.4%. On multivariable analysis, age,
      hypertension, previous ischaemic stroke, symptomatic AF and planned cardioversion
      or ablation were independent predictors of OAC use, whereas lone AF, previous
      haemorrhagic events, chronic kidney disease and admission for acute coronary
      syndrome (ACS) or non-cardiovascular causes independently predicted OAC non-use.
      Regarding the OAC type, coronary artery disease, history of heart failure, or
      valvular heart disease, planned cardioversion and non-AF reasons for admission
      independently predicted the use of vitamin K antagonists (VKAs). Wide variability
      among the European regions was observed in the use of NOACs, independently from
      other clinical factors. Conclusion: The EORP-AF Long-Term General Registry
      provides a full picture of contemporary use of OAC in European AF patients. The
      overall rate of OACs use was generally high (84.9%), and a series of factors were
      associated with the prescription of OAC. A significant geographical heterogeneity
      in prescription of NOACs vs. VKAs was evident.

PMID- 29016876
TI  - Recruit Fitness as a Predictor of Police Academy Graduation.
AB  - Background: Suboptimal recruit fitness may be a risk factor for poor performance,
      injury, illness, and lost time during police academy training. Aims: To assess
      the probability of successful completion and graduation from a police academy as
      a function of recruits' baseline fitness levels at the time of academy entry.
      Methods: Retrospective study where all available records from recruit training
      courses held (2006-2012) at all Massachusetts municipal police academies were
      reviewed and analysed. Entry fitness levels were quantified from the following
      measures, as recorded at the start of each training class: body composition, push
      ups, sit-ups, sit-and-reach, and 1.5-mile run-time. The primary outcome of
      interest was the odds of not successfully graduating from an academy. We used
      generalized linear mixed models in order to fit logistic regression models with
      random intercepts for assessing the probability of not graduating, based on entry
      level fitness. The primary analyses were restricted to recruits with complete
      entry-level fitness data. Results: The fitness measures most strongly associated
      with academy failure were lesser number of push-ups completed (odds ratio [OR] =
      5.2, 95% confidence interval [CI] 2.3-11.7, for 20 versus 41-60 push-ups) and
      slower run times (OR = 3.8, 95% CI 1.8-7.8, [1.5 mile run time of >=15'20"]
      versus [12'33" to 10'37"]). Conclusions: Baseline pushups and 1.5-mile run-time
      showed the best ability to predict successful academy graduation, especially when
      considered together. Future research should include prospective validation of
      entry-level fitness as a predictor of subsequent police academy success.

PMID- 29016875
TI  - Occupancy of Norepinephrine Transporter by Duloxetine in Human Brains Measured by
      Positron Emission Tomography with (S,S)-[18F]FMeNER-D2.
AB  - Background: The norepinephrine transporter in the brain has been targeted in the
      treatment of psychiatric disorders. Duloxetine is a serotonin and norepinephrine
      reuptake inhibitor that has been widely used for the treatment of depression.
      However, the relationship between dose and plasma concentration of duloxetine and
      norepinephrine transporter occupancy in the human brain has not been determined.
      In this study, we examined norepinephrine transporter occupancy by different
      doses of duloxetine. Methods: We calculated norepinephrine transporter
      occupancies from 2 positron emission tomography scans using (S,S)-[18F]FMeNER-D2
      before and after a single oral dose of duloxetine (20 mg, n = 3; 40 mg, n = 3; 60
      mg, n =2). Positron emission tomography scans were performed from 120 to 180
      minutes after an i.v. bolus injection of (S,S)-[18F]FMeNER-D2. Venous blood
      samples were taken to measure the plasma concentration of duloxetine just before
      and after the second positron emission tomography scan. Results: Norepinephrine
      transporter occupancy by duloxetine was 29.7% at 20 mg, 30.5% at 40 mg, and 40.0%
      at 60 mg. The estimated dose of duloxetine inducing 50% norepinephrine
      transporter occupancy was 76.8 mg, and the estimated plasma drug concentration
      inducing 50% norepinephrine transporter occupancy was 58.0 ng/mL. Conclusions:
      Norepinephrine transporter occupancy by clinical doses of duloxetine was
      approximately 30% to 40% in human brain as estimated using positron emission
      tomography with (S,S)-[18F]FMeNER-D2.

PMID- 29016877
TI  - Work-related stress assessed by a text message single-item stress question.
AB  - Background: Given the prevalence of work stress-related ill-health in the Western
      world, it is important to find cost-effective, easy-to-use and valid measures
      which can be used both in research and in practice. Aims: To examine the validity
      and reliability of the single-item stress question (SISQ), distributed weekly by
      short message service (SMS) and used for measurement of work-related stress.
      Methods: The convergent validity was assessed through associations between the
      SISQ and subscales of the Job Demand-Control-Support model, the Effort-Reward
      Imbalance model and scales measuring depression, exhaustion and sleep. The
      predictive validity was assessed using SISQ data collected through SMS. The
      reliability was analysed by the test-retest procedure. Results: Correlations
      between the SISQ and all the subscales except for job strain and esteem reward
      were significant, ranging from -0.186 to 0.627. The SISQ could also predict sick
      leave, depression and exhaustion at 12-month follow-up. The analysis on
      reliability revealed a satisfactory stability with a weighted kappa between 0.804
      and 0.868. Conclusions: The SISQ, administered through SMS, can be used for the
      screening of stress levels in a working population.

PMID- 29016878
TI  - Automatic remote monitoring utilizing daily transmissions: transmission
      reliability and implantable cardioverter defibrillator battery longevity in the
      TRUST trial.
AB  - Aims: Benefits of automatic remote home monitoring (HM) among implantable
      cardioverter defibrillator (ICD) patients may require high transmission
      frequency. However, transmission reliability and effects on battery longevity
      remain uncertain. We hypothesized that HM would have high transmission success
      permitting punctual guideline based follow-up, and improve battery longevity.
      This was tested in the prospective randomized TRUST trial. Methods and results:
      Implantable cardioverter defibrillator patients were randomized post-implant 2:1
      to HM (n = 908) (transmit daily) or to Conventional in-person monitoring
      [conventional management (CM), n = 431 (HM disabled)]. In both groups, five
      evaluations were scheduled every 3 months for 15 months. Home Monitoring
      technology performance was assessed by transmissions received vs. total possible,
      and number of scheduled HM checks failing because of missed transmissions.
      Battery longevity was compared in HM vs. CM at 15 months, and again in HM 3 years
      post-implant using continuously transmitted data. Transmission success per
      patient was 91% (median follow-up of 434 days). Overall, daily HM transmissions
      were received in 315 795 of a potential 363 450 days (87%). Only 55/3759 (1.46%)
      of unsuccessful scheduled evaluations in HM were attributed to transmission loss.
      Shock frequency and pacing percentage were similar in HM vs. CM. Fifteen month
      battery longevity was 12% greater in HM (93.2 +/- 8.8% vs. 83.5 +/- 6.0% CM, P <
      0.001). In extended follow-up of HM patients, estimated battery longevity was
      50.9 +/- 9.1% (median 52%) at 36 months. Conclusion: Automatic remote HM
      demonstrated robust transmission reliability. Daily transmission load may be
      sustained without reducing battery longevity. Home Monitoring conserves battery
      longevity and tracks long term device performance. Clinical trial registration:
      ClinicalTrials.gov; NCT00336284.

PMID- 29016882
TI  - Intra-atrial re-entrant tachycardia in patients with congenital heart disease:
      factors associated with disease severity.
AB  - Aim: Intra-atrial re-entrant tachycardia (IART) is a common complication in
      patients with congenital heart disease (CHD) and is related to increased
      morbidity and mortality. Few reports have been published about factors associated
      to IART severity. The aim of this study is to analyse factors associated to
      severe clinical presentation of IART. Methods and Results: Observational study of
      all consecutive CHD patients who underwent a first IART ablation from January
      2009 to December 2015 (94 patients, 39.4% female, and age: 36.55 +/- 14.9 years).
      Severe clinical presentation was defined as heart failure, syncope, shock,
      electromechanical dissociation (EMD), or aborted sudden death. The majority of
      patients had moderately or highly complex cardiac defect (90.4%). Types of IART
      included cavotricuspid isthmus(CTI) dependent in 51% (48), non-CTI-related in
      22.3% (20), and both types in 27.7% (26). In 38 patients (40.4%), a severe event
      occurred and in 16 (17%), the symptoms included shock, syncope, sudden death, or
      EMD. In 21 (22.3%), severe symptoms were the first manifestation of IART. In
      multivariate analysis, transposition of the great arteries (TGA) with right
      systemic ventricle (OR 5.32, 95% C.I. 1.6-7.02, P = 0.0005) and severe dilation
      of the venous atrium (VsA) (OR 4.17; 95% CI 1.4-8.12, P = 0.0009) were factors
      independently associated with severity. Conclusion: In our series of 94 CHD
      patients with a high proportion of moderately to highly complex cardiac defects,
      severe consequences of IART were frequent. Transposition of the great arteries
      with systemic right ventricle and severe dilation of VsA were independently
      associated to severity. Early invasive procedures should be considered for these
      high-risk patients.

PMID- 29016880
TI  - Evaluation of the Relative Intranasal Abuse Potential of a Hydrocodone Extended
      Release Tablet Formulated with Abuse-Deterrence Technology in Nondependent,
      Recreational Opioid Users.
AB  - Objective: To assess the intranasal abuse potential of hydrocodone extended
      release (ER) tablets developed with CIMA Abuse-Deterrence Technology compared
      with hydrocodone powder and hydrocodone bitartrate ER capsules (Zohydro ER,
      original formulation [HYD-OF]). Design: Single-dose, randomized, double-blind,
      quadruple-dummy, active- and placebo-controlled, crossover study. Setting: One US
      site. Subjects: Healthy, adult, nondependent, recreational opioid users. Methods:
      Subjects able to tolerate intranasal hydrocodone and discriminate hydrocodone
      from placebo were eligible for study enrollment. Eligible participants randomly
      received intranasal hydrocodone ER, intranasal hydrocodone powder, intranasal HYD
      OF, intact oral hydrocodone ER, and placebo. Coprimary pharmacodynamic end points
      were a maximum effect on "at the moment" Drug Liking visual analog scale and
      Overall Drug Liking visual analog scale. Pharmacokinetics and safety were
      assessed. Results: Mean maximum effect for "at the moment" Drug Liking was
      significantly (P < 0.01) lower for intranasal hydrocodone ER (72.8) compared with
      hydrocodone powder (80.2) and HYD-OF (83.2). Similar results were observed for
      Overall Drug Liking maximum effect (68.5 vs 77.1 and 79.8, respectively; P <
      0.01). Secondary end points, including balance of effects and positive, sedative,
      and other effects, were consistent with these results. Intranasal treatments
      showed significantly greater effects vs placebo, while intact oral hydrocodone ER
      was similar to placebo. For each treatment, plasma concentration-time profiles
      paralleled "at the moment" Drug Liking over time. Incidences of adverse events
      for intranasal treatments were 52% for hydrocodone ER, 53% for hydrocodone
      powder, and 61% for HYD-OF. Conclusions: The statistically significant
      differences between hydrocodone ER vs hydrocodone powder and HYD-OF for the
      primary drug liking end points indicate a lower intranasal abuse potential with
      hydrocodone ER in healthy, nondependent, recreational opioid users.

PMID- 29016883
TI  - Pharmacists' Role in Opioid Safety: A Focus Group Investigation.
AB  - Objective: The pharmacist's role and responsibilities in addressing the opioid
      epidemic have yet to be clearly defined, particularly from the patient's point of
      view. This qualitative study explores the pharmacist's role in promoting opioid
      safety from the perspective of pharmacists and patients. Design: Focus groups.
      Setting: Patient groups were held in person, and pharmacist groups were held
      online. Subjects: Oregon pharmacists (N = 19, Mage = 39.0 years, range = 26-57
      years, 58% female) and patients (N = 18, Mage = 60.1 years, range = 30-77 years,
      71% female) with current experience dispensing or receiving opioid medications.
      Methods: Pharmacists were asked about the challenges and opportunities for opioid
      safety monitoring and prescription dispensing. Patients were asked about their
      experiences accessing care, medications, and safety information. Focus group data
      were analyzed by a multidisciplinary team using an immersion-crystallization
      approach. Results: Pharmacists and patients agreed that pharmacists are
      responsible for medication safety. Pharmacists expressed discomfort filling
      potentially high-risk opioid prescriptions and noted barriers such as lack of
      clinical information and discomfort policing high-risk prescribing. Patients were
      concerned about pharmacists potentially overstepping their professional
      responsibilities by interfering with prescribers' clinical decisions.
      Conclusions: Feedback from both pharmacists and patient participants suggests
      that there is uncertainty in the degree to which pharmacists can and should
      confront the prescription opioid epidemic directly. Ambiguities in the
      pharmacist's role may be best clarified through structured training promoting
      enhanced between-party communication.

PMID- 29016879
TI  - Agonist OX40 immunotherapy improves survival in glioma-bearing mice and is
      complementary with vaccination with irradiated GM-CSF-expressing tumor cells.
AB  - Background: Glioma immunotherapy is an active area of clinical investigation.
      Glioma-associated immunosuppression remains an obstacle to efficacious
      immunotherapy, and combination approaches are likely necessary for durable
      success. OX40 is a member of the tumor necrosis factor receptor superfamily that
      is upregulated on activated lymphocytes, ligation of which results in enhanced
      activity and may be active against cancer. We sought to confirm the efficacy of
      agonist anti-OX40 immunotherapy against glioma and hypothesized that it is
      complementary with irradiated whole tumor cell vaccination. Methods: GL261 tumor
      cells were implanted into the right frontal lobes of syngeneic mice, which were
      then treated with controls, agonist anti-OX40 monoclonal antibody, vaccination
      with subcutaneous injection of irradiated granulocyte macrophage colony
      stimulating factor (GM-CSF)-expressing GL261 cells (GVAX), or vaccination +
      agonist anti-OX40 therapy. Animals were followed for survival. On day 18,
      splenocytes were harvested for enzyme-linked immunosorbent spot analyses and
      brains were harvested for immunohistochemistry and flow cytometry analyses of
      infiltrating lymphocytes. Results: Combination immunotherapy with GVAX and
      systemic agonist anti-OX40 monoclonal antibody improved survival by 14 days over
      controls (median survival 36 vs 22 days, P < 0.00005). Systemically, T helper
      cell type 1 (Th1) antitumor immunity was enhanced significantly by combination
      therapy. In the brain, combination immunotherapy increased the percentage of Th1
      CD4+ T lymphocytes and reduced the fraction that were Th2. In the brain,
      vaccination improved the ratio of CD8+ to FoxP3+ T lymphocytes, while combination
      immunotherapy reversed intracranial T-lymphocyte exhaustion, reducing their
      coexpression of programmed cell death protein 1 (PD-1) and T-cell immunoglobulin
      and mucin-domain containing-3 (TIM-3) as well as PD-1 and lymphocyte-activation
      gene 3 (LAG-3). Conclusions: Anti-OX40 immunotherapy is active against
      intracranial glioma and synergizes with GVAX. Vaccination and anti-OX40
      immunotherapy are mechanistically complementary, particularly in the glioma
      microenvironment.

PMID- 29016884
TI  - Cocaine contamination of banknotes: a review.
AB  - Background: The analysis of drug traces on banknotes with different validated
      techniques can provide important information about the types of substances that
      are used in a geographical region. The aim of our review was to investigate
      banknotes' contamination by cocaine, by its metabolite, but also by other drugs.
      Methods: A systematic literature search (English written literature) was
      conducted in MEDLINE, and Scopus, collecting studies from 1974 till 2017. The Key
      search terms included: 'banknote AND drug'; 'banknote AND cocaine'. Results: The
      literature search yielded 88 publications; 9 were included in our review. In six
      studies that showed banknotes' positivity to cocaine, the percentage ranged from
      2.5% to 100%. The concentration of cocaine ranged from 0.09 ng/note to 889
      ug/note. Benzoylecgonine was indentified only in three studies with a range from
      0.71 to 130 ng/note. Other indentified drugs were: amphetamine derivatives,
      opiates, benzodiazepines. Conclusions: Circulating banknotes could be used to
      indicate substances used in a population, and those recently introduced in a
      geographical macro-area. The identification of very high amounts of cocaine can
      provide important information for the identification of banknotes used in illegal
      trafficking.

PMID- 29016881
TI  - Ephemerality of a Spring Ephemeral Gagea lutea (L.) is Attributable to Shoot
      Senescence Induced by Free Linolenic Acid.
AB  - Spring ephemerals are a group of herbaceous plants that fulfill their life cycle
      on the floor of deciduous forests in temperate and boreal regions during a short
      period of time between snowmelt and closure of the tree canopy. Near the closure,
      these plants' shoots senesce rapidly and the plants disappear from the floor.
      Since the major role of the synchronous senescence is thought to be the recycling
      of nutrients from vegetative organs to seeds or storage organs, some endogenous
      compound that is capable of promoting senescence must be involved in the timely
      senescence. Strong senescence-promoting activity was found in extracts of shoots
      of a spring ephemeral, Gagea lutea (Liliaceae), and the activity in basal leaves
      reached a maximum just before the commencement of senescence. The active compound
      was identified as alpha-linolenic acid. The level, very low 1 week before
      flowering, increased rapidly with time and reached a maximum 1 week after
      flowering. Senescence was readily observed thereafter. The maximum amount of
      linolenic acid was >1 mmol kg FW-1 and could fully induce senescence of the
      leaves. The results suggest that the ephemerality of the plant or, in other
      words, short longevity of shoots, is brought about by the accumulation of
      linolenic acid. Programmed senescence, which can mitigate the cost of survival
      and reproduction, enables the plant to occupy a narrow niche on the forest floor.

PMID- 29016885
TI  - Endogenous Pain Modulation: Association with Resting Heart Rate Variability and
      Negative Affectivity.
AB  - Objectives: Several chronic pain syndromes are characterized by deficient
      endogenous pain modulation as well as elevated negative affectivity and reduced
      resting heart rate variability. In order to elucidate the relationships between
      these characteristics, we investigated whether negative affectivity and heart
      rate variability are associated with endogenous pain modulation in a healthy
      population. Design, Subjects, and Methods: An offset analgesia paradigm with
      noxious thermal stimulation calibrated to the individual's pain threshold was
      used to measure endogenous pain modulation magnitude in 63 healthy individuals.
      Pain ratings during constant noxious heat stimulation to the arm (15 seconds)
      were compared with ratings during noxious stimulation comprising a 1  degrees C
      rise and return of temperature to the initial level (offset trials, 15 seconds).
      Offset analgesia was defined as the reduction in pain following the 1  degrees C
      decrease relative to pain at the same time point during continuous heat
      stimulation. Results: Evidence for an offset analgesia effect could only be found
      when noxious stimulation intensity (and, hence, the individual's pain threshold)
      was intermediate (46  degrees C or 47  degrees C). Offset analgesia magnitude was
      also moderated by resting heart rate variability: a small but significant offset
      effect was found in participants with high but not low heart rate variability.
      Negative affectivity was not related to offset analgesia magnitude. Conclusions:
      These results indicate that resting heart rate variability (HRV) is related to
      endogenous pain modulation (EPM) in a healthy population. Future research should
      focus on clarifying the causal relationship between HRV and EPM and chronic pain
      by using longitudinal study designs.

PMID- 29016886
TI  - A proposed framework of supportive and palliative care for people with high-grade
      glioma.
AB  - Background: Patients with malignant high-grade glioma (HGG) have significant
      supportive and palliative care needs, yet few tailored guidelines exist to inform
      practice. This study sought to develop an HGG framework of supportive and
      palliative care informed by needs reported by patients, families, and health care
      professionals (HCPs). Methods: This study integrates a mixed-methods research
      program involving: (i) exploring experiences through systematic literature review
      and qualitative study (10 patients, 23 carers, and 36 HCPs); and (ii) an
      epidemiological cohort study (N = 1821) describing care of cases of HGG in
      Victoria, Australia using linked hospital datasets. Recommendations based on
      these studies were developed by a multidisciplinary advisory committee for a
      framework of supportive and palliative care based on the findings of (i) and
      (ii). Results: Key principles guiding framework development were that care: (i)
      aligns with patient/family caregiver needs according to illness transition
      points; (ii) involves continuous monitoring of patient/family caregiver needs;
      (iii) be proactive in response to anticipated concerns; (iv) includes routine
      bereavement support; and (v) involves appropriate partnership with
      patients/families. Framework components and resulting activities designed to
      address unmet needs were enacted at illness transition points and included
      coordination, repeated assessment, staged information provision according to the
      illness transition, proactive responses and referral systems, and specific
      regular inquiry of patients' and family caregivers' concerns. Conclusion: This
      evidence-based, collaborative framework of supportive and palliative care
      provides an approach for patients with HGG that is responsive, relevant, and
      sustainable. This conceptual framework requires evaluation in robust clinical
      trials.

PMID- 29016888
TI  - Metabolic heterogeneity and plasticity of glioma stem cells in a mouse
      glioblastoma model.
AB  - Background: Glioblastomas have been shown to rely on glycolysis as an energy
      source. However, recent evidence suggests that at least a subset of glioma cells
      with stem cell-like properties can thrive on oxidative phosphorylation. It
      remains unclear whether both metabolic phenotypes support tumor propagation, if
      they are independent, and how stable they are. The present study investigated
      these questions with the use of isogenic murine glioma stem cells (GSCs).
      Methods: GSCs were established from tumors formed by Ink4a/Arf-null, H-RasV12
      expressing glioma-initiating cells that differed in extracellular acidification
      potential. Metabolic characteristics of GSCs were determined by measurement of
      glucose, oxygen, and glutamine uptake, ATP content, and lactate production.
      Effects of metabolic inhibitors and changes in oxygen or nutrient availability on
      lactate production and tumorsphere growth were also determined. Results: GSCs
      were found either to consume more glucose and produce more lactate or to consume
      more oxygen and maintain a higher ATP content depending on the metabolic
      characteristics of the tumor cells of origin. The latter, mitochondrial-type GSCs
      increased lactate production after treatment with the oxidative phosphorylation
      inhibitor oligomycin or phenformin. Exposure to hypoxia also increased lactate
      production and expression of glycolysis-related enzymes and metabolites in
      mitochondrial-type GSCs in a reversible manner. Conclusions: Both glycolytic and
      mitochondrial-type energy production can sustain tumor propagation by isogenic
      GSCs. Whereas both phenotypes can be independent and stable, cells that rely on
      oxidative phosphorylation can also switch to a more glycolytic phenotype in
      response to metabolic stress, suggesting that plasticity is a further
      characteristic of GSC metabolism.

PMID- 29016890
TI  - CHA2DS2-VASc score and blood biomarkers to identify patients with atrial high
      rate episodes and paroxysmal atrial fibrillation: the role of TIMP-4 regulation
      Authors' reply.

PMID- 29016889
TI  - ARGONAUTE10 Inhibits In Vitro Shoot Regeneration Via Repression of miR165/166 in
      Arabidopsis thaliana.
AB  - Many plant cells retain their totipotency when cultured in vitro. The regulation
      of shoot regeneration from in vitro culture involves a number of gene products,
      but the nature of the associated post-transcriptional events remains largely
      unknown. Here, the post-transcriptional regulator ARGONAUTE10 (AGO10), a protein
      which is specifically expressed in the explant during the period when pro-shoot
      apical meristems (SAMs) are forming, has been known to inhibit shoot
      regeneration. In in vitro cultured explants of the loss-of-function mutant ago10,
      a much larger than normal number of SAMs was formed and, in these, the stem cell
      marker genes WUSCHEL, CLAVATA3 and SHOOT MERISTEMLESS were all strongly
      expressed. AGO10 repressed the accumulation of the microRNAs miR165/166, thereby
      up-regulating a suite of HD-ZIP III genes. The overproduction of miR166 was shown
      to promote shoot regeneration, while the absence of miR165/166 message resulted
      in a blockage to shoot regeneration and only a partial rescue of the phenotype of
      the ago10 mutant. The major conclusion was that the shoot regeneration inhibition
      determined by AGO10 functions via the repression of miR165/166.

PMID- 29016887
TI  - Phase I/II trial of vorinostat combined with temozolomide and radiation therapy
      for newly diagnosed glioblastoma: results of Alliance N0874/ABTC 02.
AB  - Background: Vorinostat, a histone deacetylase (HDAC) inhibitor, has shown
      radiosensitizing properties in preclinical studies. This open-label, single-arm
      trial evaluated the maximum tolerated dose (MTD; phase I) and efficacy (phase II)
      of vorinostat combined with standard chemoradiation in newly diagnosed
      glioblastoma. Methods: Patients received oral vorinostat (300 or 400 mg/day) on
      days 1-5 weekly during temozolomide chemoradiation. Following a 4- to 6-week
      rest, patients received up to 12 cycles of standard adjuvant temozolomide and
      vorinostat (400 mg/day) on days 1-7 and 15-21 of each 28-day cycle. Association
      between vorinostat response signatures and progression-free survival (PFS) and
      overall survival (OS) was assessed based on RNA sequencing of baseline tumor
      tissue. Results: Phase I and phase II enrolled 15 and 107 patients, respectively.
      The combination therapy MTD was vorinostat 300 mg/day and temozolomide 75
      mg/m2/day. Dose-limiting toxicities were grade 4 neutropenia and thrombocytopenia
      and grade 3 aspartate aminotransferase elevation, hyperglycemia, fatigue, and
      wound dehiscence. The primary efficacy endpoint in the phase II cohort, OS rate
      at 15 months, was 55.1% (median OS 16.1 mo), and consequently, the study did not
      meet its efficacy objective. Most common treatment-related grade 3/4 toxicities
      in the phase II component were lymphopenia (32.7%), thrombocytopenia (28.0%), and
      neutropenia (21.5%). RNA expression profiling of baseline tumors (N = 76)
      demonstrated that vorinostat resistance (sig-79) and sensitivity (sig-139)
      signatures had a reverse and positive association with OS/PFS, respectively.
      Conclusions: Vorinostat combined with standard chemoradiation had acceptable
      tolerability in newly diagnosed glioblastoma. Although the primary efficacy
      endpoint was not met, vorinostat sensitivity and resistance signatures could
      facilitate patient selection in future trials.

PMID- 29016891
TI  - 'Hidden' Terpenoids in Plants: Their Biosynthesis, Localization and Ecological
      Roles.
AB  - Terpenoids are the largest group of plant specialized (secondary) metabolites.
      These naturally occurring chemical compounds are highly diverse in chemical
      structure. Although there have been many excellent studies of terpenoids, most
      have focused on compounds built solely of isoprene units. Plants, however, also
      contain many 'atypical' terpenoids, such as glycosylated volatile terpenes and
      composite-type terpenoids, the latter of which are synthesized by the coupling of
      isoprene units on aromatic compounds. This mini review describes these 'hidden'
      terpenoids, providing an overview of their biosynthesis, localization, and
      biological and ecological activities.

PMID- 29016892
TI  - Pain in Patients with Different Dementia Subtypes, Mild Cognitive Impairment, and
      Subjective Cognitive Impairment.
AB  - Objective: To assess the pain prevalence, pain intensity, and pain medication use
      in older patients with a diagnosed subtype of dementia, mild cognitive impairment
      (MCI), or subjective cognitive impairment (SCI). Design: Cross-sectional.
      Setting: Outpatient memory clinics. Subjects: In total, 759 patients with
      Alzheimer's disease (AD), vascular dementia, mixed AD and vascular pathology
      (MD), frontotemporal dementia, dementia with Lewy Bodies, MCI, or SCI. Methods:
      Self-reported presence and intensity of pain, prescribed medication, and related
      descriptive variables were given for each group. To compare groups on prevalence
      of pain, logistic regression analyses were adjusted for age, gender, and mood.
      Differences in pain intensity were tested using a Kruskall-Wallis test, and
      differences in analgesic use with chi-square analyses. Results: Pain prevalence
      ranged from 34% in MD to 50% in SCI. AD (odds ratio [OR] = 0.56, 95% confidence
      interval [CI] = 0.34-0.93) and MD (OR = 0.45, CI = 0.20-0.98) patients were less
      likely to report pain than SCI patients. The self-reported pain intensity did not
      differ between groups. In total, 62.5% of patients did not use any analgesic
      medication despite being in pain, which did not differ significantly between
      groups. Conclusion: Outpatient memory clinic patients with mild to moderate AD
      and MD are less likely to report pain than patients with SCI. No difference in
      self-reported pain intensity was present. The high percentage of patients with
      and without dementia who do not use analgesics when in pain raises the question
      of whether pain treatment is adequate in older patients.

PMID- 29016893
TI  - Efficacy, Safety, and Feasibility of the Morphine Microdose Method in Community
      Based Clinics.
AB  - Objectives: The goal of this study was to assess the success of the morphine
      microdose method in a community pain clinic setting by monitoring follow-up
      frequency, dose escalation, and monotherapy/polytherapy ratio. The morphine
      microdose method involves a pretrial reduction or elimination of systemic opioids
      followed by a period of abstinence. Intrathecal (IT) morphine is then started at
      doses of less than 0.2 mg per day. Systemic opioid abstinence is then continued
      after pump implant and IT morphine monotherapy. Design: Retrospective review of
      medical records. Setting: Private and academic pain clinic practices. Subjects:
      Chronic noncancer pain patients. Methods: We reviewed the charts of 60 patients
      who had completed a microdose regimen and had an IT pump implanted between June
      11, 2008, and October 11, 2014. During IT therapy, dose change over time, pain
      scores, side effects, max dose, and duration were recorded. Results: The majority
      of patients (35/60, 58%) were successfully managed solely on morphine microdose
      monotherapy. These patients did not require additional oral therapy. There was a
      significant reduction in mean pain scores, from 7.4 +/- 0.32 before microdose
      therapy to 4.8 +/- 0.3 after microdose therapy. Conclusions: Microdose therapy
      achieved analgesia, improved safety, and avoided systemic side effects. The
      safety of IT therapy was increased by using a lower concentration (2 mg/mL) and
      lower daily doses (<3 mg/d) of morphine. Furthermore, microdose therapy was
      feasible, safe, and cost-effective in the outpatient setting.

PMID- 29016895
TI  - The Accuracy of a Fibromyalgia Diagnosis in General Practice.
AB  - Objective: To compare the characteristics of people with fibromyalgia (FM) with
      those with other forms of nonmalignant chronic pain. Design: A prospective cohort
      study conducted in a chronic pain management clinic within an academic medical
      center. Setting: Many symptoms of the chronic pain syndrome FM are common to
      other pain or musculoskeletal syndromes. FM may be misdiagnosed by clinicians.
      Subjects: Thirty-three patients with a working diagnosis of FM were identified:
      26 (78.8%) participated in the study. They were matched by age (mean = 53.0
      years) and gender (80.8% female) to a control group with other forms of chronic
      nonmalignant pain. Methods: Standardized physical examinations for FM were
      undertaken using the 1990 and revised 2010 American College of Rheumatology (ACR)
      guidelines. The groups were compared using diagnoses of psychiatric disorders and
      responses to the Pain Disability Index, Personal Health Questionnaire, Revised
      Fibromyalgia Impact Questionnaire, and Rapid Estimate Adult Literacy in Medicine.
      Results: The most common psychiatric disorders were depression (44.4%) and
      anxiety (27.3%). Incidence of at least one psychiatric condition was 80.8%, and
      the only difference (P = 0.002) between the two populations was the mean number
      of tender points: 5.6 (+/-4.2) vs controls 3.2 (+/-2.2). Only three (11.5%)
      participants with a prior diagnosis of FM fulfilled the 1990 ACR diagnostic
      criteria, increasing to 38.5% when the 2010 criteria were applied; however, 46.1%
      of controls also met the revised diagnostic criteria. Conclusions: FM is commonly
      misdiagnosed: all patients with a working diagnosis should be reassessed and
      reviewed to ensure that the most appropriate treatment is provided.

PMID- 29016896
TI  - Poor working conditions and work stress among Canadian sex workers.
AB  - Background: While sex work is often considered the world's oldest profession,
      there remains a dearth of research on work stress among sex workers (SWs) in
      occupational health epidemiological literature. A better understanding of the
      drivers of work stress among SWs is needed to inform sex work policy, workplace
      models and standards. Aims: To examine the factors that influence work stress
      among SWs in Metro Vancouver. Methods: Analyses drew from a longitudinal cohort
      of SWs, known as An Evaluation of Sex Workers' Health Access (AESHA) (2010-14). A
      modified standardized 'work stress' scale, multivariable linear regression with
      generalized estimating equations was used to longitudinally examine the factors
      associated with work stress. Results: In multivariable analysis, poor working
      conditions were associated with increased work stress and included workplace
      physical/sexual violence (beta = 0.18; 95% confidence interval (CI) 0.06, 0.29),
      displacement due to police (beta = 0.26; 95% CI 0.14, 0.38), working in public
      spaces (beta = 0.73; 95% CI 0.61, 0.84). Older (beta = -0.02; 95% CI -0.03, 
      0.01) and Indigenous SWs experienced lower work stress (beta = -0.25; 95% CI 
      0.43, -0.08), whereas non-injection (beta = 0.32; 95% CI 0.14, 0.49) and
      injection drug users (beta = 0.17; 95% CI 0.03, 0.31) had higher work stress.
      Conclusions: Vancouver-based SWs' work stress was largely shaped by poor work
      conditions, such as violence, policing, lack of safe workspaces. There is a need
      to move away from criminalized approaches which shape unsafe work conditions and
      increase work stress for SWs. Policies that promote SWs' access to the same
      occupational health, safety and human rights standards as workers in other labour
      sectors are also needed.

PMID- 29016894
TI  - Diffuse high-grade gliomas with H3 K27M mutations carry a dismal prognosis
      independent of tumor location.
AB  - Background: The novel entity of "diffuse midline glioma, H3 K27M-mutant" has been
      defined in the 2016 revision of the World Health Organization (WHO)
      classification of tumors of the central nervous system (CNS). Tumors of this
      entity arise in CNS midline structures of predominantly pediatric patients and
      are associated with an overall dismal prognosis. They are defined by K27M
      mutations in H3F3A or HIST1H3B/C, encoding for histone 3 variants H3.3 and H3.1,
      respectively, which are considered hallmark events driving gliomagenesis.
      Methods: Here, we characterized 85 centrally reviewed diffuse gliomas on midline
      locations enrolled in the nationwide pediatric German HIT-HGG registry regarding
      tumor site, histone 3 mutational status, WHO grade, age, sex, and extent of tumor
      resection. Results: We found 56 H3.3 K27M-mutant tumors (66%), 6 H3.1 K27M-mutant
      tumors (7%), and 23 H3-wildtype tumors (27%). H3 K27M-mutant gliomas shared an
      aggressive clinical course independent of their anatomic location. Multivariate
      regression analysis confirmed the significant impact of the H3 K27M mutation as
      the only independent parameter predictive of overall survival (P = 0.009). In H3
      K27M-mutant tumors, neither anatomic midline location nor histopathological
      grading nor extent of tumor resection had an influence on survival. Conclusion:
      These results substantiate the clinical significance of considering diffuse
      midline glioma, H3 K27M-mutant, as a distinct entity corresponding to WHO grade
      IV, carrying a universally fatal prognosis.

PMID- 29016897
TI  - Genome-Wide Analysis and Expression Profiles of the MYB Genes in Brachypodium
      distachyon.
AB  - MYB transcription factors are widespread in plants and play key roles in plant
      development. Although MYB transcription factors have been thoroughly
      characterized in many plants, genome-wide analysis of the MYB gene family has not
      yet been undertaken in Brachypodium distachyon. In this study, 122 BdMYB
      transcription factors were identified, comprising 85 MYB-R2R3, 34 MYB-related and
      three MYB-R1R2R3. Phylogenetic analysis showed that BdMYBs, OsMYBs and AtMYBs
      with similar functions were clustered in the same subgroup, and the phylogenetic
      relationships of BdMYB transcription factors were supported by highly conserved
      motifs and gene structures. Two cis-elements were found in the promoters of BdMYB
      genes. One is related to plant growth/development, the other is related to stress
      responses. Gene Ontology (GO) analysis indicated that most of the BdMYB genes are
      involved in various biological processes. The chromosome distribution pattern
      strongly indicated that genome-wide tandem and segment duplication mainly
      contributed to the expansion of the BdMYB gene family. Synteny analysis showed
      that 56, 58 and 61 BdMYB genes were orthologous to rice, maize and sorghum,
      respectively. We further demonstrated that BdMYB genes have evolved under strong
      purifying selection. The expression profiles indicated that most BdMYB genes
      might participate in floral development and respond to abiotic stresses.
      Additionally, 338 pairs of proteins were predicted to interact by constructing
      the interaction network. This work laid the foundation and provided clues for
      understanding the biological functions of these transcription factors.

PMID- 29016898
TI  - To the Editor.

PMID- 29016899
TI  - Single Nucleotide Polymorphisms Associated with Pain Sensitivity After
      Laparoscopic Cholecystectomy.
AB  - Objective: To systematically evaluate variations in single-nucleotide
      polymorphisms within 13 candidate pain genes in patients differing in phenotype
      characteristics based on a composite measure of pain sensitivity. Methods: In a
      case-control study, 149 patients scheduled for laparoscopic cholecystectomy were
      individually categorized according to preoperative pain sensitivity and
      postoperative pain intensity. Cases (pain group) reported cannulation-induced
      pain intensity higher than 2.0, together with postoperative pain intensity of 7.0
      or higher (visual analog scale [VAS] units), and controls (low-pain group)
      reported cannulation-induced pain intensity of 2.0 or lower, together with
      postoperative pain intensity lower than 4.0 (VAS units). Genotyping of exomes was
      performed in 32 case and 25 control patients compared with respect to variations
      within 13 candidate pain genes. Results: There were no statistically significant
      differences in single nucleotide polymorphisms (SNPs) within the candidate genes
      between the case and control groups, but minor allele SNPs in the ABCB1 and COMT
      genes were more common in patients with higher levels of pain sensitivity and
      intensity. Conclusion: In this candidate gene study, based on a composite measure
      of pain sensitivity, no variations reached statistical significance after
      correction for multiple testing, most likely due to the large number of markers
      analyzed and few patients. Nevertheless, the results suggest a possible genetic
      contribution of single-nucleotide polymorphisms within the ABCB1 and COMT genes
      in individuals with higher levels of pain sensitivity.

PMID- 29016901
TI  - The Roles of the Sole Activator-Type Auxin Response Factor in Pattern Formation
      of Marchantia polymorpha.
AB  - Cell division patterning is important to determine body shape in plants. Nuclear
      auxin signaling mediated by AUXIN RESPONSE FACTOR (ARF) transcription factors
      affects plant growth and development through regulation of cell division,
      elongation and differentiation. The evolutionary origin of the ARF-mediated
      pathway dates back to at least the common ancestor of bryophytes and other land
      plants. The liverwort Marchantia polymorpha has three phylogenetically distinct
      ARFs: MpARF1, the sole 'activator' ARF; and MpARF2 and MpARF3, two 'repressor'
      ARFs. Genetic screens for auxin-resistant mutants revealed that loss of MpARF1
      function conferred auxin insensitivity. Mparf1 mutants showed reduced auxin
      inducible gene expression and various developmental defects, including thallus
      twisting and gemma malformation. We further investigated the role of MpARF1 in
      gemma development, which is traceable at the cellular level. In wild-type plants,
      a gemma initial first undergoes several transverse divisions to generate a single
      celled stalk and a gemma proper, followed by rather synchronous longitudinal
      divisions in the latter. Mparf1 mutants often contained multicelled stalks and
      showed defects in the execution and timing of the longitudinal divisions. While
      wild-type gemmae finally generate two meristem notches, Mparf1 gemmae displayed
      various numbers of ectopic meristems. These results suggest that MpARF1 regulates
      formative cell divisions and axis formation through auxin responses. The
      mechanism for activator ARF regulation of pattern formation may be shared in land
      plants and therefore important for the general acquisition of three-dimensional
      body plans.

PMID- 29016902
TI  - Validation of the PTSD-8 Scale in Chronic Pain Patients.
AB  - Objectives: The aim was to validate the short PTSD-8 scale against the Structured
      Clinical Interview (SCID-1) for post-traumatic stress disorder and to test the
      latent structure of post-traumatic stress disorder in chronic pain patients.
      Methods: A total of 51 chronic nonmalignant pain patients exposed to a traumatic
      event were consecutively recruited from a multidisciplinary pain center. All
      participants answered a baseline questionnaire followed by the PTSD-8 and the
      diagnostic interview for PTSD. Finally, the latent structure of PTSD-8 was tested
      in a large cohort of 419 patients with chronic nonmalignant pain using
      confirmatory factor analysis (CFA). Results: In total, 33.3% had a diagnosis of
      PTSD. A good overall accuracy was found validating the PTSD-8 against the
      diagnostic interview. Convergent validity was indicated as the PTSD-8 correlated
      strongly with scores of depression and anxiety. The results of the CFA for the
      PTSD-8 three-factor structure provided excellent fit for the eight post-traumatic
      stress disorder symptoms. Conclusions: Overall, the results showed that the PTSD
      8 is a valid short screening tool to assess possible post-traumatic stress
      disorder among patients with chronic pain. In addition, the PTSD-8 scale
      comprises all of the upcoming ICD-11 post-traumatic stress disorder symptoms
      within its eight items. Thus, the PTSD-8 is likely also to measure the proposed
      ICD-11 post-traumatic stress disorder.

PMID- 29016900
TI  - Is the blood-brain barrier really disrupted in all glioblastomas? A critical
      assessment of existing clinical data.
AB  - The blood-brain barrier (BBB) excludes the vast majority of cancer therapeutics
      from normal brain. However, the importance of the BBB in limiting drug delivery
      and efficacy is controversial in high-grade brain tumors, such as glioblastoma
      (GBM). The accumulation of normally brain impenetrant radiographic contrast
      material in essentially all GBM has popularized a belief that the BBB is
      uniformly disrupted in all GBM patients so that consideration of drug
      distribution across the BBB is not relevant in designing therapies for GBM.
      However, contrary to this view, overwhelming clinical evidence demonstrates that
      there is also a clinically significant tumor burden with an intact BBB in all
      GBM, and there is little doubt that drugs with poor BBB permeability do not
      provide therapeutically effective drug exposures to this fraction of tumor cells.
      This review provides an overview of the clinical literature to support a central
      hypothesis: that all GBM patients have tumor regions with an intact BBB, and cure
      for GBM will only be possible if these regions of tumor are adequately treated.

PMID- 29016903
TI  - Screening for latent tuberculosis in UK health care workers.
AB  - Background: Active tuberculosis (TB) infection was diagnosed in two health care
      workers (HCWs) originally from high-incidence countries at a National Health
      Service (NHS) hospital trust in Northern England. In response, the trust screened
      current clinical employees from countries with a high TB prevalence for active
      and latent TB infection (LTBI). Aims: To identify the number of HCWs, within the
      organization, who are at risk of TB infection. Methods: Clinical employees from
      countries with a high TB prevalence (those described by the World Health
      Organization as having an incidence of >40 cases per 100000 populations) were
      reviewed. Employees were identified via human resource systems and occupational
      health records, from which nationality or country of birth was identified. A
      letter was sent to identified employees advising of the rationale for a reviewed
      screening process and inviting them to attend for an interferon-gamma release
      assay (IGRA) blood test. Results: A total of 587 clinical staff were identified
      as fitting the criteria of clinical HCWs from high-incidence countries. Of 469
      HCWs screened, 27% screened positive using IGRA. This represented 4% of the total
      clinical workforce for the organization. Conclusions: A considerable proportion
      of the workforce at this NHS hospital trust had previously undiagnosed LTBI,
      carrying a risk of conversion to active disease. Further action, such as
      treatment of LTBI or increased workforce awareness of symptoms of active disease,
      could help to reduce the risk of transmission of TB to patients and the need for
      associated 'look-back' exercises.

PMID- 29016904
TI  - Arabinogalactan Proteins Accumulate in the Cell Walls of Searching Hyphae of the
      Stem Parasitic Plants, Cuscuta campestris and Cuscuta japonica.
AB  - Stem parasitic plants (Cuscuta spp.) develop a specialized organ called a
      haustorium to penetrate their hosts' stem tissues. To reach the vascular tissues
      of the host plant, the haustorium needs to overcome the physical barrier of the
      cell wall, and the parasite-host interaction via the cell wall is a critical
      process. However, the cell wall components responsible for the establishment of
      parasitic connections have not yet been identified. In this study, we
      investigated the spatial distribution patterns of cell wall components at a
      parasitic interface using parasite-host complexes of Cuscuta campestris
      Arabidopsis thaliana and Cuscuta japonica-Glycine max. We focused on
      arabinogalactan proteins (AGPs), because AGPs accumulate in the cell walls of
      searching hyphae of both C. campestris and C. japonica. We found more AGPs in
      elongated haustoria than in pre haustoria, indicating that AGP accumulation is
      developmentally regulated. Using in situ hybridization, we identified five genes
      in C. campestris that encode hyphal-expressed AGPs that belong to the fasciclin
      like AGP (FLA) family, which were named CcFLA genes. Three of the five CcFLA
      genes were expressed in the holdfast, which develops on the Cuscuta stem
      epidermis at the attachment site for the host's stem epidermis. Our results
      suggest that AGPs are involved in hyphal elongation and adhesion to host cells,
      and in the adhesion between the epidermal tissues of Cuscuta and its host.

PMID- 29016905
TI  - Relative Abuse of Crush-Resistant Prescription Opioid Tablets via Alternative
      Oral Modes of Administration.
AB  - Objective: Some crush-resistant tablet formulations (CRTs) reduce prescription
      opioid abuse by nonoral routes of administration (ROAs), especially insufflation
      and injection, while oral abuse increases. Oral abuse involving product
      manipulation vs swallowing whole for CRTs and comparators was examined. Methods:
      Abuse by oral modes of administration (e.g., swallowing whole, chewing,
      dissolving in the mouth), was examined using the ASI-MV, a computerized, clinical
      interview for adults in substance abuse treatment from January 2009 to March
      2015. CRTs (reformulated oxycodone extended-release [ER], reformulated
      oxymorphone ER, and tapentadol ER) were compared with non-CRT versions, morphine
      ER, and oxycodone immediate-release single entity. Analyses employed descriptive
      statistics and logistic regression. Results: Among 364,329 unique assessments,
      18,135 patients reported oral abuse of the CRTs and comparators examined. CRTs
      had a higher prevalence of oral abuse involving product manipulation than
      comparators (P < 0.0001) among all abusers of product. Oral abuse involving
      product manipulation for CRTs was greater among the subset of patients reporting
      oral abuse and significantly higher than comparators (P < 0.003). CRTs were
      significantly less likely than comparators to be swallowed whole (P < 0.0001) and
      significantly more likely to be chewed (P < 0.003). CRTs were more likely to be
      dissolved in the mouth than most comparators. Conclusions: Results suggest the
      need for abuse-deterrent formulations designed to reduce abuse by oral
      administration with product manipulation, such as chewing. Advances in this area
      may reduce the overall abuse of prescription opioids and interrupt the
      progression from abuse by swallowing whole to oral administration involving
      product manipulation and other ROAs.

PMID- 29016840
TI  - 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and
      surgical ablation of atrial fibrillation.

PMID- 29016907
TI  - Clinical value of different QRS-T angle expressions.
AB  - Aims: Increased spatial angle between QRS complex and T wave loop orientations
      has repeatedly been shown to predict cardiac risk. However, there is no consensus
      on the methods for the calculation of the angle. This study compared the
      reproducibility and predictive power of three most common ways of QRS-T angle
      assessment. Methods and results: Electrocardiograms of 352 healthy subjects, 941
      survivors of acute myocardial infarction (MI), and 605 patients recorded prior to
      the implantation of automatic defibrillator [implantable cardioverter
      defibrillator (ICD)] were used to obtain QRS-T angle measurements by the maximum
      R to T (MRT), area R to T (ART), and total cosine R to T (TCRT) methods. The
      results were compared in terms of physiologic reproducibility and power to
      predict mortality in the cardiac patients during 5-year follow-up. Maximum R to T
      results were significantly less reproducible compared to the other two methods.
      Among both survivors of acute MI and ICD recipients, TCRT method was
      statistically significantly more powerful in predicting mortality during follow
      up. Among the acute MI survivors, increased spatial QRS-T angle (TCRT assessment)
      was particularly powerful in predicting sudden cardiac death with the area under
      the receiver operator characteristic of 78% (90% confidence interval 63-90%).
      Among the ICD recipients, TCRT also predicted mortality significantly among
      patients with prolonged QRS complex duration when the spatial orientation of the
      QRS complex is poorly defined. Conclusion: The TCRT method for the assessment of
      spatial QRS-T angle appears to offer important advantages in comparison to other
      methods of measurement. This approach should be included in future clinical
      studies of the QRS-T angle. The TCRT method might also be a reasonable candidate
      for the standardization of the QRS-T angle assessment.

PMID- 29016906
TI  - YUCCA9-Mediated Auxin Biosynthesis and Polar Auxin Transport Synergistically
      Regulate Regeneration of Root Systems Following Root Cutting.
AB  - Recovery of the root system following physical damage is an essential issue for
      plant survival. An injured root system is able to regenerate by increases in
      lateral root (LR) number and acceleration of root growth. The horticultural
      technique of root pruning (root cutting) is an application of this response and
      is a common garden technique for controlling plant growth. Although root pruning
      is widely used, the molecular mechanisms underlying the subsequent changes in the
      root system are poorly understood. In this study, root pruning was employed as a
      model system to study the molecular mechanisms of root system regeneration.
      Notably, LR defects in wild-type plants treated with inhibitors of polar auxin
      transport (PAT) or in the auxin signaling mutant auxin/indole-3-acetic
      acid19/massugu2 were recovered by root pruning. Induction of IAA19 following root
      pruning indicates an enhancement of auxin signaling by root pruning. Endogenous
      levels of IAA increased after root pruning, and YUCCA9 was identified as the
      primary gene responsible. PAT-related genes were induced after root pruning, and
      the YUCCA inhibitor yucasin suppressed root regeneration in PAT-related mutants.
      Therefore, we demonstrate the crucial role of YUCCA9, along with other redundant
      YUCCA family genes, in the enhancement of auxin biosynthesis following root
      pruning. This further enhances auxin transport and activates downstream auxin
      signaling genes, and thus increases LR number.

PMID- 29016909
TI  - Corrigenda.

PMID- 29016911
TI  - Opioid Resistance Associated with CYP3A4 Hyperactivity and COMT Polymorphism in
      an Oncological Patient.

PMID- 29016912
TI  - Are Gadolinium-Based Contrast Media Safe Alternatives for Spine Procedures?

PMID- 29016908
TI  - The effect of age on fitness among female firefighters.
AB  - Background: The physical demands of firefighting require both cardiovascular and
      muscular fitness, which both decline with age. While much has been published on
      age-related changes among male firefighters (FFs), data on female FFs are
      lacking. Aims: To describe cardiorespiratory fitness (CRF) and muscular fitness
      in a sample of female career FFs ranging in age from 25 to 60 years and determine
      whether ageing affects their achievement of the current recommended professional
      CRF standards of 12 metabolic equivalents (METs). Methods: Data were collected on
      female FFs over an 11-year period. A cross-sectional analysis using one-way
      analysis of variance with Bonferroni post hoc comparisons was used to compare age
      groups. Results: There were 96 study participants. Maximum METs was significantly
      higher (P < 0.01) in the 25- to 34-year age group (14.6 +/- 2.1) compared with
      the 35-44 age group (12.9 +/- 2.0 METs) and the 45-54 age group (12.2 +/- 1.8
      METs, P < 0.001). While the mean values of all measured age groups met or
      exceeded the 12-MET profession standard, as many as one-third of FFs <45 years of
      age and 43% of FFs >45 years of age fell below the benchmark of 12 METs. Muscular
      fitness as measured by maximum number of push-ups, sit-ups and back endurance was
      not significantly different between age groups. Conclusions: Fire departments
      should recognize and take steps to ensure all female FFs maintain CRF and
      muscular fitness throughout their careers.

PMID- 29016910
TI  - Left atrial appendage occluder implantation in Europe: indications and
      anticoagulation post-implantation. Results of the European Heart Rhythm
      Association Survey.
AB  - The aim of this EP Wire survey was to assess the indications and anticoagulation
      strategies post-left atrial appendage occluder (LAAO) implantation for stroke
      prevention in patients with non-valvular atrial fibrillation in Europe. A total
      of 33 centres in 13 European countries completed the survey. All centres were
      members of the European Heart Rhythm Association Electrophysiology Research
      Network. Left atrial appendage occluder procedures were performed by
      electrophysiologists in 52% of the centres and by interventional cardiologists in
      the remaining centres. The EP Wire survey has revealed that the most common
      indications for LAAO are stroke prevention in patients at high thrombo-embolic
      risk and absolute contraindications to oral anticoagulation (OAC) therapy or a
      history of bleeding. Early- and long-term post-implantation anticoagulation
      strategies in patients with and without device thrombosis were very heterogeneous
      between centres with most strategies not being supported by the randomized
      trials. In patients without contraindications to OAC, 41% of the centres would
      prescribe no therapy at all after 6 months following LAAO implantation. In
      patients with LAA thrombus during follow-up and patients with absolute
      contraindications to OAC, management was highly heterogeneous and included
      aspirin, clopidogrel, non-vitamin K antagonist oral anticoagulants, low molecular
      weight heparin, surgery, unfractionated heparin, or no therapy.

PMID- 29016914
TI  - Spinal Cord Injury During Attempted Cervical Interlaminar Epidural Injection of
      Steroids.
AB  - Background: Interlaminar cervical epidural injections are commonly performed in
      the practice of interventional pain medicine. Injury to the spinal cord following
      injection into the substance of the cord is a known complication of this
      procedure, but it has rarely been reported and illustrated in the literature.
      Objective: To describe and analyze a case where an inadvertent injection of
      contrast medium into the cervical spinal cord occurred. Highlighted is the
      dissonance between how the procedure was performed and published guidelines for
      its performance. Presented is the first published oblique fluoroscopic image of
      an intramedullary injection. Conclusions: By recognizing the potential
      complications of a procedure, and by describing means of avoiding those
      complications, practice guidelines serve to reduce the risk, and thereby the
      incidence of complications. Deviation from established best practice guidelines
      reinstates risks of complications that can be avoided.

PMID- 29016916
TI  - Sensitization to cow's milk protein in a dairy worker.
AB  - Background: Repeated skin exposure and inhalation of milk proteins may lead to
      IgE-mediated sensitization, normally manifested at the site of contact. Although
      this is a phenomenon predominantly found in children, it has also been observed
      in adults. Aims: To describe a case of a worker who, after being exposed to milk
      proteins for many years, eventually experienced episodes of anaphylaxis. Case
      report: A 62-year-old worker experienced severe episodes of anaphylaxis following
      the intake of dairy products. He had worked in the dairy industry for 17 years,
      where he was exposed to dried milk every day. Conclusions: This case report
      illustrates how continued exposure to milk proteins, either by skin contact or
      inhalation, may lead to sensitization which could result in severe manifestations
      of anaphylaxis.

PMID- 29016917
TI  - Cannabis for the Treatment of Chronic Pain in the Era of an Opioid Epidemic: A
      Symposium-Based Review of Sociomedical Science.
AB  - Objective: This manuscript reviews medical literature published pertaining to the
      management of chronic pain with medical marijuana therapy (MMJ), with an emphasis
      on the social, medical, and legal aspects of therapy. Design: Narrative review of
      peer-reviewed literature. Methods: The 3rd Symposium on Controlled Substances and
      Their Alternatives for the Treatment of Pain was held in Boston on February 27,
      2016, with a focus on MMJ for the treatment of chronic pain. Invited speakers had
      diverse backgrounds, including pain management, addiction psychiatry, neurology,
      and legal authorities. The purpose of this conference and this subsequent
      narrative review is to provide a medical, legal, and logistical framework for
      physicians and other health care providers to refer to when considering the
      initiation of medical marijuana therapy. Results: The invited speakers each
      covered a unique aspect of MMJ therapy for the treatment of chronic pain. These
      presentations highlighted the current data for and against the use of MMJ as a
      pain therapy. Optimal patient selection and screening, in addition to policy
      developments, were discussed. Conclusions: Increasing interest in MMJ for chronic
      pain underscores a need for primary care and pain physicians to better understand
      the indications and evidence for its use free from cultural bias. Given a lack of
      full conclusive clinical utility, continued research is needed to better
      understand how to best utilize MMJ therapy for the treatment of chronic pain.
      Policy initiatives, such as enumerated indications, should follow medical science
      in order to prevent another abused substance epidemic.

PMID- 29016918
TI  - A Critical View on ABC Transporters and Their Interacting Partners in Auxin
      Transport.
AB  - Different subclasses of ATP-binding cassette (ABC) transporters have been
      implicated in the transport of native variants of the phytohormone auxin. Here,
      the putative, individual roles of key members belonging to the ABCB, ABCD and
      ABCG families, respectively, are highlighted and the knowledge of their assumed
      expression and transport routes is reviewed and compared with their mutant
      phenotypes. Protein-protein interactions between ABC transporters and regulatory
      components during auxin transport are summarized and their importance is
      critically discussed. There is a focus on the functional interaction between
      members of the ABCB family and the FKBP42, TWISTED DWARF1, acting as a chaperone
      during plasma membrane trafficking of ABCBs. Further, the mode and relevance of
      functional ABCB-PIN interactions is diagnostically re-evaluated. A new
      nomenclature describing precisely the most likely ABCB-PIN interaction scenarios
      is suggested. Finally, available tools for the detection and prediction of ABC
      transporter interactomes are summarized and the potential of future ABC
      transporter interactome maps is highlighted.

PMID- 29016915
TI  - Drought Tolerance Conferred in Soybean (Glycine max. L) by GmMYB84, a Novel R2R3
      MYB Transcription Factor.
AB  - MYB-type transcription factors (MYB TFs) play diverse roles in plant development
      and stress responses. However, the mechanisms underlying the actions of MYB TFs
      during stress response remain unclear. In this study we identified a R2R3-MYB TF
      in soybean (Glycine max), denoted GmMYB84, which contributes to drought
      resistance. Expression of GmMYB84 was induced by drought, salt stress, H2O2 and
      ABA. Compared with the wild type (WT), GmMYB84-overexpressing soybean mutants (OE
      lines) exhibited enhanced drought resistance with a higher survival rate, longer
      primary root length, greater proline and reactive oxygen species (ROS) contents,
      higher antioxidant enzyme activities [peroxidase (POD), catalase (CAT) and
      superoxide dismutase (SOD)], a lower dehydration rate and reduced malondialdehyde
      (MDA) content. We also found that ROS could induce SOD/POD/CAT activity in OE
      lines. In particular, we found that the optimal level of ROS is required for
      GmMYB84 to modulate primary root elongation. Some ROS-related genes were up
      regulated under abiotic stress in GmMYB84 transgenic plants compared with the WT.
      Furthermore, electrophoretic mobility shift assay and luciferase reporter
      analysis demonstrated that GmMYB84 binds directly to the promoter of GmRBOHB-1
      and GmRBOHB-2 genes. Based on this evidence, we propose a model for how GmMYB84,
      H2O2 and antioxidant enzymes work together to control root growth under both
      optimal and drought stress conditions.

PMID- 29016913
TI  - Phytochelatin Synthase has Contrasting Effects on Cadmium and Arsenic
      Accumulation in Rice Grains.
AB  - Phytochelatin (PC) synthesis has been well demonstrated as a major metal
      tolerance mechanism in Arabidopsis thaliana, whereas its contribution to long
      distance element transport especially in monocots remains elusive. Using rice as
      a cereal model, we examined physiological roles of Oryza sativa phytochelatin
      synthase 1 (OsPCS1) in the distribution and detoxification of arsenic (As) and
      cadmium (Cd), two toxic elements associated with major food safety concerns.
      First, we isolated four different transcript variants of OsPCS1 as well as one
      from OsPCS2. Quantitative real-time reverse transcription-PCR (RT-PCR) of each
      OsPCS transcript in rice seedlings suggested that expression of OsPCS1full, the
      longest OsPCS1 variant, was most abundant, followed by OsPCS2. Heterologous
      expression of OsPCS variants in PCS-deficient mutants of Schizosaccharomyces
      pombe and A. thaliana suggested that OsPCS1full possessed PCS activity in
      response to As(III) and Cd while the activity of other PCS variants was very low.
      To address physiological functions in toxic element tolerance and accumulation,
      two independent OsPCS1 mutant rice lines (a T-DNA and a Tos17 insertion line)
      were identified. The OsPCS1 mutants exhibited increased sensitivity to As(III)
      and Cd in hydroponic experiments, showing the importance of OsPCS1-dependent PC
      synthesis for rice As(III) and Cd tolerance. Elemental analyses of rice plants
      grown in soil with environmentally relevant As and Cd concentrations showed
      increased As accumulation and decreased Cd accumulation in grains of the T-DNA
      line. The Tos17 mutant also exhibited the reduced Cd accumulation phenotype.
      These contrasting effects on As and Cd distribution to grains suggest the
      existence of at least partially distinct PC-dependent pathways for As and Cd.

PMID- 29016919
TI  - Challenges of developing small-molecule kinase inhibitors for brain tumors and
      the need for emphasis on free drug levels.
AB  - Despite biological rationale and significant clinical study, the pursuit of small
      molecule kinase inhibitors for the treatment of brain cancers has had very
      limited success. This Advance-in-Brief discusses the need for drugs to achieve
      free brain penetration to engage their targets where CNS tumors reside. This need
      to achieve free, as opposed to total, drug concentrations in the brain may be a
      contributing factor to why so many small-molecule kinase inhibitors have not
      realized success in the neuro-oncology setting. For kinase targets of interest
      for brain cancer, either the vast majority of small-molecule inhibitors have data
      suggesting that free brain penetration would be limited or there are inadequate
      data to suggest that free brain penetration could be expected. Therefore, kinase
      targets of interest in the treatment of brain cancers may be inadequately
      assessed due to a lack of freely brain-penetrant inhibitors available for
      clinical study. Encouraging recent drug discovery efforts that focused on
      achieving free brain penetration for cancers in the CNS are highlighted. Still,
      further efforts are needed to enable thorough clinical evaluation of biological
      hypotheses.

PMID- 29016920
TI  - The objective lens of the electron microscope with correction of spherical and
      axial chromatic aberrations.
AB  - The paper describes the principle of operation of a relatively simple aberration
      corrector for the transmission electron microscope objective lens. The electron
      optical system of the aberration corrector consists of the two main elements: an
      electrostatic mirror with rotational symmetry and a magnetic deflector formed by
      the round-shaped magnetic poles. The corrector operation is demonstrated by
      calculations on the example of correction of basic aberrations of the well-known
      objective lens with a bell-shaped distribution of the axial magnetic field. Two
      of the simplest versions of the corrector are considered: a corrector with a two
      electrode electrostatic mirror and a corrector with a three-electrode
      electrostatic mirror. It is shown that using the two-electrode mirror one can
      eliminate either spherical or chromatic aberration of the objective lens, without
      changing the value of its linear magnification. Using a three-electrode mirror,
      it is possible to eliminate spherical and chromatic aberrations of the objective
      lens simultaneously, which is especially important in designing electron
      microscopes with extremely high resolution.

PMID- 29016921
TI  - Atomic and nanoscale imaging of a cellulose nanofiber and Pd nanoparticles
      composite using lower-voltage high-resolution TEM.
AB  - We have examined the advanced application of transmission electron microscopy
      (TEM) for the structural characterization of a composite of cellulose nanofiber
      (CNF) and palladium (Pd) nanoparticles. In the present study, we focused on
      electron-irradiation damage and optimization of high-resolution TEM imaging of
      the composite. The investigation indicates that the CNF breaks even under low
      electron-dose conditions at an acceleration voltage of 200 kV. We then applied
      lower-voltage TEM at 60 kV using a spherical aberration corrector and a
      monochromator, in order to reduce electron-irradiation damage and improve the
      spatial resolution. The TEM observation achieved high-resolution imaging and
      revealed the existence of small Pd nanoparticles, around 2 nm in diameter,
      supported on the CNF. It is considered that the use of a monochromator in
      combination with spherical aberration correction contributed to the atomic and
      nanoscale imaging of the composite, owing to the improvement of the information
      limit under a lower-acceleration voltage.

PMID- 29016922
TI  - Morphologic mechanisms of increased vascular permeability of triolein emulsion to
      the blood-brain barrier.
AB  - Triolein emulsion has been known to increase vascular permeability in the brain
      when it is infused into the carotid artery. The purpose of this study was to
      identify the morphologic mechanism of increased vascular permeability in brain
      induced by infusion of emulsified triolein into the carotid artery by
      transmission electron microscopy (TEM). Triolein emulsion was infused into the
      carotid artery of rats. TEM using lanthanum tracer was used to evaluate
      morphologic changes in endothelium with a focus on transcytotic vesicles and
      tight junction opening. The treat group showed multiple transcytotic vesicles
      containing lanthanum tracer within endothelium on TEM. TEM also revealed that
      lanthanum tracer entered neural interstitium through tight junctions between
      capillary endothelial cells infrequently in the treat group. No evidence of
      transcytotic vesicles containing lanthanum tracer or lanthanum leakage through
      tight junctions was observed in the control group. Transcytosis and the opening
      of tight junctions appears the pathway for vascular permeability enhancement by
      triolein. This result could be utilized in studies on the blood-brain barrier and
      by those searching for chemotherapeutic methods that deliver anti-tumor agents to
      normally drug inaccessible organs.

PMID- 29016923
TI  - Surface morphology and dislocation characteristics near the surface of 4H-SiC
      wafer using multi-directional scanning transmission electron microscopy.
AB  - To improve the reliability of silicon carbide (SiC) electronic power devices, the
      characteristics of various kinds of crystal defects should be precisely
      understood. Of particular importance is understanding the correlation between the
      surface morphology and the near surface dislocations. In order to analyze the
      dislocations near the surface of 4H-SiC wafers, a dislocation analysis protocol
      has been developed. This protocol consists of the following process: (1)
      inspection of surface defects using low energy scanning electron microscopy
      (LESEM), (2) identification of small and shallow etch pits using KOH low
      temperature etching, (3) classification of etch pits using LESEM, (4) specimen
      preparation of several hundred nanometer thick sample using the in-situ focused
      ion beam micro-sampling(r) technique, (5) crystallographic analysis using the
      selected diffraction mode of the scanning transmission electron microscope
      (STEM), and (6) determination of the Burgers vector using multi-directional STEM
      (MD-STEM). The results show a correlation between the triangular terrace shaped
      surface defects and an hexagonal etch pit arising from threading dislocations,
      linear shaped surface defects and elliptical shaped etch pits arising from basal
      plane dislocations. Through the observation of the sample from two orthogonal
      directions via the MD-STEM technique, a basal plane dislocation is found to
      dissociate into an extended dislocation bound by two partial dislocations. A
      protocol developed and presented in this paper enables one to correlate near
      surface defects of a 4H-SiC wafer with the root cause dislocations giving rise to
      those surface defects.

PMID- 29016924
TI  - Basics and applications of ELNES calculations.
AB  - The electron energy loss near edge structures (ELNES) appearing in an electron
      energy loss spectrum obtained through transmission electron microscopy (TEM) have
      the potential to unravel atomic and electronic structures with sub-nano meter
      resolution. For this reason, TEM-ELNES has become one of the most powerful
      analytical methods in materials research. On the other hand, theoretical
      calculations are indispensable in interpreting the ELNES spectrum. Here, the
      basics and applications of one-particle, two-particle and multi-particle ELNES
      calculations are reviewed. A key point for the ELNES calculation is the proper
      introduction of the core-hole effect. Some applications of one-particle ELNES
      calculations to huge systems of more than 1000 atoms, and complex systems, such
      as liquids, are reported. In the two-particle calculations, the importance of the
      correct treatment of the excitonic interaction is demonstrated in calculating the
      low-energy ELNES, for example at the Li-K edge. In addition, an unusually strong
      excitonic interactions in the O-K edge of perovskite oxides is identified. The
      multi-particle calculations are necessary to reproduce the multiplet structures
      appearing at the transition metal L2,3-edges and rare-earth M4,5-edges.
      Applications to dilute magnetic semiconductors and Li-ion battery materials are
      presented. Furthermore, beyond the 'conventional' ELNES calculations, theoretical
      calculations of electron/X-ray magnetic circular dichroism (MCD) and the
      vibrational information in ELNES, are reported.

PMID- 29016925
TI  - Divergent evolution of temozolomide resistance in glioblastoma stem cells is
      reflected in extracellular vesicles and coupled with radiosensitization.
AB  - Background: Glioblastoma (GBM) is almost invariably fatal due to failure of
      standard therapy. The relapse of GBM following surgery, radiation, and systemic
      temozolomide (TMZ) is attributed to the ability of glioma stem cells (GSCs) to
      survive, evolve, and repopulate the tumor mass, events on which therapy exerts a
      poorly understood influence. Methods: Here we explore the molecular and cellular
      evolution of TMZ resistance as it emerges in vivo (xenograft models) in a series
      of human GSCs with either proneural (PN) or mesenchymal (MES) molecular
      characteristics. Results: We observed that the initial response of GSC-initiated
      intracranial xenografts to TMZ is eventually replaced by refractory growth
      pattern. Individual tumors derived from the same isogenic GSC line expressed
      divergent and complex profiles of TMZ resistance markers, with a minor
      representation of O6-methylguanine DNA methyltransferase (MGMT) upregulation. In
      several independent TMZ-resistant tumors originating from MES GSCs we observed a
      consistent diminution of mesenchymal features, which persisted in cell culture
      and correlated with increased expression of Nestin, decline in transglutaminase 2
      and sensitivity to radiation. The corresponding mRNA expression profiles
      reflective of TMZ resistance and stem cell phenotype were recapitulated in the
      transcriptome of exosome-like extracellular vesicles (EVs) released by GSCs into
      the culture medium. Conclusions: Intrinsic changes in the tumor-initiating cell
      compartment may include loss of subtype characteristics and reciprocal
      alterations in sensitivity to chemo- and radiation therapy. These observations
      suggest that exploiting therapy-induced changes in the GSC phenotype and
      alternating cycles of therapy may be explored to improve GBM outcomes.

PMID- 29016927
TI  - Clinical Use of Pregabalin in General Practice in Catalonia, Spain: A Population
      Based Cross-Sectional Study.
AB  - Objective: The aim of this study was to determine the pattern of use of
      pregabalin and the appropriateness of treatment, so that interventions could be
      designed to improve various clinical approaches to the use of pregabalin to
      include unlicensed indications. Design: A descriptive, cross-sectional,
      multicenter study was performed between April 2014 and January 2015. Setting:
      Fifty-three primary health care centers covering 1,250,000 inhabitants. Subjects:
      A total of 10,155 patients with pregabalin prescriptions. Methods: Demographic
      (gender, age) and clinical (licensed indications for pregabalin, treatment
      duration, dosing schedule, diagnoses, kidney function, previous treatment with
      pregabalin, and additional drug treatment combined with pregabalin) variables
      obtained from health records were studied. The indicators were related to the
      daily dose of pregabalin, diagnoses, and treatment. Results: A total of 64.2% of
      patients treated with pregabalin were female (mean age = 62.3 years; SD = 15.2
      years). Twenty-nine patients were younger than age 18 years. A total of 68.2% of
      patients were taking pregabalin for an appropriate indication, 45.2% were using
      pregabalin off-label for bone and joint pain, and 15.1% were using pregabalin for
      fibromyalgia. A total of 71.9% of patients started treatment with pregabalin
      without previously using firstline drugs, such as amitriptyline or gabapentin,
      and 66% of active treatments had been initiated during the year before the study.
      In 47% of patients with glomerular filtration rates lower than 15 mL/min, the
      dose exceeded the maximum. Conclusions: Our study reveals that pregabalin is used
      for unlicensed indications and often when firstline drugs have not been trialed
      and suggests that better routines in diagnosis and prescription may improve
      treatment outcomes. Our study also provides novel information about the use of
      doses of pregabalin that are higher than recommended for patients with renal
      impairment.

PMID- 29016926
TI  - Activation of WEE1 confers resistance to PI3K inhibition in glioblastoma.
AB  - Background: Oncogenic activation of phosphatidylinositol-3 kinase (PI3K)
      signaling plays a pivotal role in the development of glioblastoma (GBM). However,
      pharmacological inhibition of PI3K has so far not been therapeutically successful
      due to adaptive resistance through a rapid rewiring of cancer cell signaling.
      Here we identified that WEE1 is activated after transient exposure to PI3K
      inhibition and confers resistance to PI3K inhibition in GBM. Methods: Patient
      derived glioma-initiating cells and established GBM cells were treated with PI3K
      inhibitor or WEE1 inhibitor alone or in combination, and cell proliferation was
      evaluated by CellTiter-Blue assay. Cell apoptosis was analyzed by TUNEL, annexin
      V staining, and blotting of cleaved caspase-3 and cleaved poly(ADP-ribose)
      polymerase. Both subcutaneous xenograft and orthotropic xenograft studies were
      conducted to evaluate the effects of the combination on tumorigenesis; the tumor
      growth was monitored by bioluminescence imaging, and tumor tissue was analyzed by
      immunohistochemistry to validate signaling changes. Results: PI3K inhibition
      activates WEE1 kinase, which in turn phosphorylates cell division control protein
      2 homolog (Cdc2) at Tyr15 and inhibits Cdc2 activity, leading to G2/M arrest in a
      p53-independent manner. WEE1 inhibition abrogated the G2/M arrest and propelled
      cells to prematurely enter into mitosis and consequent cell death through mitotic
      catastrophe and apoptosis. Additionally, combination treatment significantly
      suppressed tumor growth in a subcutaneous model but not in an intracranial model
      due to limited blood-brain barrier penetration. Conclusions: Our findings
      highlight WEE1 as an adaptive resistant gene activated after PI3K inhibition, and
      inhibition of WEE1 potentiated the effectiveness of PI3K targeted inhibition,
      suggesting that a combinational inhibition of WEE1 and PI3K might allow
      successful targeted therapy in GBM.

PMID- 29016928
TI  - Integrating Plant Science and Crop Modeling: Assessment of the Impact of Climate
      Change on Soybean and Maize Production.
AB  - Increasing global CO2 emissions have profound consequences for plant biology, not
      least because of direct influences on carbon gain. However, much remains
      uncertain regarding how our major crops will respond to a future high CO2 world.
      Crop model inter-comparison studies have identified large uncertainties and
      biases associated with climate change. The need to quantify uncertainty has drawn
      the fields of plant molecular physiology, crop breeding and biology, and climate
      change modeling closer together. Comparing data from different models that have
      been used to assess the potential climate change impacts on soybean and maize
      production, future yield losses have been predicted for both major crops. When
      CO2 fertilization effects are taken into account significant yield gains are
      predicted for soybean, together with a shift in global production from the
      Southern to the Northern hemisphere. Maize production is also forecast to shift
      northwards. However, unless plant breeders are able to produce new hybrids with
      improved traits, the forecasted yield losses for maize will only be mitigated by
      agro-management adaptations. In addition, the increasing demands of a growing
      world population will require larger areas of marginal land to be used for maize
      and soybean production. We summarize the outputs of crop models, together with
      mitigation options for decreasing the negative impacts of climate on the global
      maize and soybean production, providing an overview of projected land-use change
      as a major determining factor for future global crop production.

PMID- 29016932
TI  - Systemic Effects of Epidural Corticosteroid Injection.

PMID- 29016930
TI  - Beau's lines.

PMID- 29016929
TI  - Trivalent CAR T cells overcome interpatient antigenic variability in
      glioblastoma.
AB  - Background: Glioblastoma (GBM) is the most common primary malignant brain cancer,
      and is currently incurable. Chimeric antigen receptor (CAR) T cells have shown
      promise in GBM treatment. While we have shown that combinatorial targeting of 2
      glioma antigens offsets antigen escape and enhances T-cell effector functions,
      the interpatient variability in surface antigen expression between patients
      hinders the clinical impact of targeting 2 antigen pairs. This study addresses
      targeting 3 antigens using a single CAR T-cell product for broader application.
      Methods: We analyzed the surface expression of 3 targetable glioma antigens
      (human epidermal growth factor receptor 2 [HER2], interleukin-13 receptor subunit
      alpha-2 [IL13Ralpha2], and ephrin-A2 [EphA2]) in 15 primary GBM samples.
      Accordingly, we created a trivalent T-cell product armed with 3 CAR molecules
      specific for these validated targets encoded by a single universal (U)
      tricistronic transgene (UCAR T cells). Results: Our data showed that co-targeting
      HER2, IL13Ralpha2, and EphA2 could overcome interpatient variability by a
      tendency to capture nearly 100% of tumor cells in most tumors tested in this
      cohort. UCAR T cells made from GBM patients' blood uniformly expressed all 3 CAR
      molecules with distinct antigen specificity. UCAR T cells mediated robust immune
      synapses with tumor targets forming more polarized microtubule organizing centers
      and exhibited improved cytotoxicity and cytokine release over best monospecific
      and bispecific CAR T cells per patient tumor profile. Lastly, low doses of UCAR T
      cells controlled established autologous GBM patient derived xenografts (PDXs) and
      improved survival of treated animals. Conclusion: UCAR T cells can overcome
      antigenic heterogeneity in GBM and lead to improved treatment outcomes.

PMID- 29016931
TI  - The Tri-Institutional Pain Registry-Analysis of Outpatient Pain Management at a
      Specialized Cancer Center.
AB  - Objectives: The Outpatient Pain Clinics at Memorial Sloan Kettering Cancer Center
      participated in developing a pain registry to gain insight on the referral and
      management of cancer pain as related to demographic information, cancer history,
      prescription records, and interventional pain procedures stored in the
      institutional database. Methods: Five cohorts (subsets of one another) were
      defined and compared to describe demographics and differences in management and
      outcomes by age, race, sex, and cancer type. Clinic patients were compared with
      the entire institution to determine factors associated with better pain relief
      and reduced side effects. Results: A small percentage were referred to a pain
      specialist. A total of 1,043 patients completed 3,544 surveys. Compared with the
      institution, there were higher proportions of patients age 51 to 60 years,
      nonwhites, and patients with thoracic, abdominal, and head and neck cancers.
      Medical management controlled pain with three drug categories in 40% of visits.
      Short-acting opioids were the only category that statistically provided good pain
      relief with fewer side effects. Pain scores were improved with increasing opioid
      dose. Management differed by sex, age, and race; women consistently had lower
      doses of opioids, poorer pain control, more side effects, and were prescribed a
      greater variety of medications. Conclusions: A limited set of medications was
      required to manage most patients in the clinic, supporting the continued place of
      opioids and the World Health Organization analgesic ladder in managing cancer
      pain. Women may need a more nuanced approach for obtaining the best balance of
      pain relief and side effects.

PMID- 29016933
TI  - Rice Inositol Polyphosphate Kinase (OsIPK2) Directly Interacts with OsIAA11 to
      Regulate Lateral Root Formation.
AB  - The plant hormone auxin controls many aspects of plant growth and development by
      promoting the degradation of Auxin/Indole-3-acetic acid (Aux/IAA) proteins. The
      domain II (DII) of Aux/IAA proteins is sufficient for eliciting the degradation
      by directly interacting with the auxin receptor F-box protein TIR1 to form a
      TIR1/AFBs-Aux/IAA complex in an auxin-dependent manner. However, the underlying
      mechanisms of fine-tuning Aux/IAA degradation by auxin stimuli remain to be
      elucidated. Here, we show that OsIPK2, a rice (Oryza sativa) inositol
      polyphosphate kinase, directly interacts with an Aux/IAA protein OsIAA11 to
      repress its degradation. In a rice protoplast transient expression system, the
      auxin-induced degradation of Myc-OsIAA11 fusion was delayed by co-expressed GFP
      OsIPK2 proteins. Furthermore, expressing additional OsIPK2 or its N-terminal
      amino acid sequence enhanced the accumulation of OsIAA11 proteins in transgenic
      plants, which in turn caused defects in lateral root formation and auxin
      response. Taken together, we identify a novel co-factor of Aux/IAA in auxin
      signaling and demonstrate its role in regulating lateral root development.

PMID- 29016935
TI  - Co-ordinated Changes in the Accumulation of Metal Ions in Maize (Zea mays ssp.
      mays L.) in Response to Inoculation with the Arbuscular Mycorrhizal Fungus
      Funneliformis mosseae.
AB  - Arbuscular mycorrhizal symbiosis is an ancient interaction between plants and
      fungi of the phylum Glomeromycota. In exchange for photosynthetically fixed
      carbon, the fungus provides the plant host with greater access to soil nutrients
      via an extensive network of root-external hyphae. Here, to determine the impact
      of the symbiosis on the host ionome, the concentration of 19 elements was
      determined in the roots and leaves of a panel of 30 maize varieties, grown under
      phosphorus-limiting conditions, with or without inoculation with the fungus
      Funneliformis mosseae. Although the most recognized benefit of the symbiosis to
      the host plant is greater access to soil phosphorus, the concentration of a
      number of other elements responded significantly to inoculation across the panel
      as a whole. In addition, variety-specific effects indicated the importance of
      plant genotype to the response. Clusters of elements were identified that varied
      in a co-ordinated manner across genotypes, and that were maintained between non
      inoculated and inoculated plants.

PMID- 29016934
TI  - microRNA-7 upregulates death receptor 5 and primes resistant brain tumors to
      caspase-mediated apoptosis.
AB  - Background: MicroRNAs (miRs) are known to play a pivotal role in tumorigenesis,
      controlling cell proliferation and apoptosis. In this study, we investigated the
      potential of miR-7 to prime resistant tumor cells to apoptosis in glioblastoma
      (GBM). Methods: We created constitutive and regulatable miR-7 expression vectors
      and utilized pharmacological inhibition of caspases and genetic loss of function
      to study the effect of forced expression of miR-7 on death receptor (DR) pathways
      in a cohort of GBM with established resistance to tumor necrosis factor apoptosis
      inducing ligand (TRAIL) and in patient-derived primary GBM stem cell (GSC) lines.
      We engineered adeno-associated virus (AAV)-miR-7 and stem cell (SC) releasing
      secretable (S)-TRAIL and utilized real time in vivo imaging and neuropathology to
      understand the effect of the combined treatment of AAV-miR-7 and SC-S-TRAIL in
      vitro and in mouse models of GBM from TRAIL-resistant GSC. Results: We show that
      expression of miR-7 in GBM cells results in downregulation of epidermal growth
      factor receptor and phosphorylated Akt and activation of nuclear factor-kappaB
      signaling. This leads to an upregulation of DR5, ultimately priming resistant GBM
      cells to DR-ligand, TRAIL-induced apoptotic cell death. In vivo, a single
      administration of AAV-miR-7 significantly decreases tumor volumes, upregulates
      DR5, and enables SC-delivered S-TRAIL to eradicate GBM xenografts generated from
      patient-derived TRAIL-resistant GSC, significantly improving survival of mice.
      Conclusions: This study identifies the unique role of miR-7 in linking cell
      proliferation to death pathways that can be targeted simultaneously to
      effectively eliminate GBM, thus presenting a promising strategy for treating GBM.

PMID- 29016936
TI  - Work-sharing and male employees' mental health during an economic recession.
AB  - Background: One approach to reducing occupational stress during an economic
      recession is to share work amongst employees. This may include reducing
      employees' working hours to avoid redundancies. Aims: To examine whether work
      sharing influenced the psychosocial work environment and depressive symptoms
      encountered by Japanese employees, and to determine which psychosocial factors
      predict employees' mental health during an economic recession. Methods: A survey
      was performed in a Japanese manufacturing company at the beginning (T1) and end
      (T2) of a 6-month period during the 2008 economic recession using the validated
      Job Content Questionnaire (JCQ) and Self-Rating Depression Scale (SDS). Results:
      Three hundred and thirty-six male employees completed the questionnaire. Twenty
      four per cent of participants showed depressive symptoms at T1. Despite
      reductions in employees' working hours and job strain (P < 0.001), SDS scores
      showed no change after 6 months. Logistic regression analyses showed that low
      social support between the two surveys was associated with depressive symptoms at
      T2 after adjusting for demographic, lifestyle, workplace factors, scheduled
      working hours and depressive symptoms at T1. Conclusions: Reductions in job
      strain did not affect employees' depressive symptoms. Employees with low social
      support during the study had a significantly higher risk of having depressive
      symptoms. These findings indicate that social and emotional support within the
      workplace is important during the work-sharing period.

PMID- 29016937
TI  - Screening for Insomnia: An Observational Study Examining Sleep Disturbances,
      Headache Characteristics, and Psychiatric Symptoms in Patients Visiting a
      Headache Center.
AB  - Objective: Effective treatments for insomnia exist, but few physicians treating
      headaches have routine methods for screening for insomnia. We sought to 1)
      describe the migraine characteristics and comorbid conditions that can affect
      sleep and 2) assess their relationships with positive screens on the Insomnia
      Severity Index (ISI). Methods: This is a retrospective cross-sectional study of
      the migraine and sleep characteristics of new patients in our headache center
      (August 15, 2015-October 28, 2015) who were suspected of having migraines based
      on the new patient intake questionnaire. The questionnaire included the ISI,
      questions about headache characteristics, and screens for psychiatric
      comorbidities. Two tailed t tests and analysis of variance evaluated
      relationships between headache characteristics, comorbidities, and ISI score.
      Results: A total of 61 new patients were suspected to have migraines. The mean
      number of headache days per month was 11.6. Only 41% of patients reported
      sleeping seven or more hours; 49.2% had an ISI of 15 or higher (positive screen).
      Regarding the insomnia scores, there were no differences between moderate and
      severe headache pain, between episodic and chronic headaches, and between the
      associated symptoms (nausea/vomiting, photophobia, phonophobia; P > 0.05).
      Musculoskeletal pain (18.7 vs 13.8, P = 0.027), depression (rho = 0.610), and
      general anxiety (rho = 0.436) were associated with higher ISI scores.
      Conclusions: Nearly half of the patients with suspected migraines in a headache
      center screened positive for insomnia, independent of whether they had episodic
      or chronic headaches. This would generate a substantial number of cognitive
      behavioral therapy for insomnia (CBT-I) referrals. Given the strong association
      between comorbid musculoskeletal pain, depression, anxiety, and insomnia, we
      suggest prioritizing CBT-I referral for those patients regardless of their
      headache frequency.

PMID- 29016940
TI  - Developing a tool for identifying high-risk employers for inspection.
AB  - Background: Workers' Compensation Board (WCB) data and other information are
      sometimes used to calculate an 'Occupational Health and Safety (OHS) index' as a
      way of identifying businesses considered 'high risk' to be inspected as part of
      enforcement work. However, no evidence on the validity of this index exists.
      Aims: To evaluate the performance of the Alberta OHS index, a 'score' based
      largely on WCB claims data, and to see if an index calculated using different
      information could perform better. Methods: Data from the Alberta Compliance
      Management Information System database, 2011-2015, and WCB claim database, 2007
      2014, were retrieved. Issuing 'stop work' or 'stop use' orders in inspections was
      defined as a proxy of high-risk outcome. The performance of the current and a
      modified OHS index were assessed using receiver operating characteristics (ROC)
      and regression analyses. Results: In large employers, neither the current nor the
      modified OHS index was particularly effective in identifying 'high risk'
      employers with the area under the ROC curve (AROC) of 0.55 (95% confidence
      interval [CI] 0.52-0.57; P < 0.001) and 0.59 (95% CI 0.57-0.62; P < 0.001),
      respectively. In small employers, neither index seemed very effective with an
      AROC of 0.54 (95% CI 0.53-0.56; P < 0.001) and 0.55 (95% CI 0.53-0.56; P <
      0.001), respectively. These results were consistent in subgroup analyses of
      assignments without specific initiatives, both in large and small employers.
      Conclusions: Neither the current nor a modified OHS index seemed to effectively
      identify high-risk employers. Heterogeneous results in large and small employers
      suggest that approaches to different-sized employers are appropriate.

PMID- 29016939
TI  - Molecular autopsy of sudden unexplained deaths reveals genetic predispositions
      for cardiac diseases among young forensic cases.
AB  - Aims: Coronary artery disease accounts for the majority of sudden cardiac deaths
      (SCD) in the older population whereas cardiomyopathies and arrhythmogenic
      abnormalities predominate in younger SCD victims (<35 years) with a significant
      genetic component. The elucidation of the pathogenetic cause of death might be
      relevant for the prevention of further deaths within affected families. Aim of
      this study was to determine the portion of underlying genetic heart diseases
      among unexplained putative SCD cases from a large German forensic department.
      Methods and results: We included 10 forensic cases of sudden unexplained death
      (SUD) victims aged 19-40 years, who died by SCD due to forensic autopsy. DNA was
      analysed by next generation panel sequencing of 174 candidate genes for
      channelopathies and cardiomyopathies. Cardiological examinations, genetic
      counselling, and subsequent genetic testing were offered to all affected
      families. We identified within 1 year 10 cases of SUD among 172 forensic cases.
      Evidence for a genetic disposition was found in 8 of 10 (80%) cases, with
      pathogenic mutations in 3 and variants of uncertain significance in 5 of SCD
      cases. Subsequent selective screening of family members revealed two additional
      mutation carriers. Conclusion: The study provides strong evidence that molecular
      genetics improves the post mortem diagnosis of fatal genetic heart diseases among
      SUD victims. Molecular genetics should be integrated in forensic and pathological
      routine practice.

PMID- 29016938
TI  - Preclinical investigation of combined gene-mediated cytotoxic immunotherapy and
      immune checkpoint blockade in glioblastoma.
AB  - Background: Combined immunotherapy approaches are promising cancer treatments. We
      evaluated anti-programmed cell death protein 1 (PD-1) treatment combined with
      gene-mediated cytotoxic immunotherapy (GMCI) performed by intratumoral injection
      of a prodrug metabolizing nonreplicating adenovirus (AdV-tk), providing in situ
      chemotherapy and immune stimulation. Methods: The effects of GMCI on PD ligand 1
      (PD-L1) expression in glioblastoma were investigated in vitro and in vivo. The
      efficacy of the combination was investigated in 2 syngeneic mouse glioblastoma
      models (GL261 and CT-2A). Immune infiltrates were analyzed by flow cytometry.
      Results: GMCI upregulated PD-L1 expression in vitro and in vivo. Both GMCI and
      anti-PD-1 increased intratumoral T-cell infiltration. A higher percentage of long
      term survivors was observed in mice treated with combined GMCI/anti-PD-1 relative
      to single treatments. Long-term survivors were protected from tumor rechallenge,
      demonstrating durable memory antitumor immunity. GMCI led to elevated interferon
      gamma positive T cells and a lower proportion of exhausted double positive
      PD1+TIM+CD8+ T cells. GMCI also increased PD-L1 levels on tumor cells and
      infiltrating macrophages/microglia. Our data suggest that anti-PD-1 treatment
      improves the effectiveness of GMCI by overcoming interferon-induced PD-L1
      mediated inhibitory signals, and GMCI improves anti-PD-1 efficacy by increasing
      tumor-infiltrating T-cell activation. Conclusions: Our data show that the
      GMCI/anti-PD-1 combination is well tolerated and effective in glioblastoma mouse
      models. These results support evaluation of this combination in glioblastoma
      patients.

PMID- 29016941
TI  - Perceived effect of deployment on families of UK military personnel.
AB  - Background: In the UK, little is known about the perceived effects of deployment,
      on military families, from military personnel in theatre. Aims: To investigate
      military personnel's perceptions of the impact of deployment on intimate
      relationships and children. Methods: Deployed service personnel who were in a
      relationship, and who had children, completed a survey while deployed on combat
      operations. Data were taken from four mental health surveys carried out in Iraq
      in 2009 and Afghanistan in 2010, 2011 and 2014. Results: Among 4265 participants,
      after adjusting for military and social-demographic covariates, perceiving that
      deployment had a negative impact on intimate relationships and children was
      associated with psychological distress, and traumatic stress symptoms. Military
      personnel who reported being in danger of being injured or killed during
      deployment, were more likely to report a perceived negative effect of deployment
      on their intimate relationships. Reservists were less likely to report a
      perceived negative impact of deployment on their children compared with regulars.
      Military personnel who themselves planned to separate from their partner were
      more likely to report psychological distress, and stressors at home. Perceived
      insufficient support from the Ministry of Defence was associated with poor mental
      health, and holding a junior rank. Conclusions: Deployed UK military personnel
      with symptoms of psychological distress, who experienced stressors at home, were
      especially likely to perceive that their family were inadequately supported by
      the military. Those planning to separate from their partner were at increased
      risk of suffering with mental health problems while deployed.

PMID- 29016942
TI  - BEN3/BIG2 ARF GEF is Involved in Brefeldin A-Sensitive Trafficking at the trans
      Golgi Network/Early Endosome in Arabidopsis thaliana.
AB  - Membrane traffic at the trans-Golgi network (TGN) is crucial for correctly
      distributing various membrane proteins to their destination. Polarly localized
      auxin efflux proteins, including PIN-FORMED1 (PIN1), are dynamically transported
      between the endosomes and the plasma membrane (PM) in the plant cells. The
      intracellular trafficking of PIN1 protein is sensitive to the fungal toxin
      brefeldin A (BFA), which is known to inhibit guanine nucleotide exchange factors
      for ADP ribosylation factors (ARF GEFs) such as GNOM. However, the molecular
      details of the BFA-sensitive trafficking pathway have not been fully revealed. In
      a previous study, we identified an Arabidopsis mutant BFA-visualized endocytic
      trafficking defective 3 (ben3) which exhibited reduced sensitivity to BFA in
      terms of BFA-induced intracellular PIN1 agglomeration. Here, we show that BEN3
      encodes a member of BIG family ARF GEFs, BIG2. BEN3/BIG2 tagged with fluorescent
      proteins co-localized with markers for the TGN/early endosome (EE). Inspection of
      conditionally induced de novo synthesized PIN1 confirmed that its secretion to
      the PM is BFA sensitive, and established BEN3/BIG2 as a crucial component of this
      BFA action at the level of the TGN/EE. Furthermore, ben3 mutation alleviated BFA
      induced agglomeration of another TGN-localized ARF GEF, BEN1/MIN7. Taken
      together, our results suggest that BEN3/BIG2 is an ARF GEF component, which
      confers BFA sensitivity to the TGN/EE in Arabidopsis.

PMID- 29016943
TI  - Radiologic progression of glioblastoma under therapy-an exploratory analysis of
      AVAglio.
AB  - Background: In this exploratory analysis of AVAglio, a randomized phase III
      clinical study that investigated the addition of bevacizumab (Bev) to
      radiotherapy/temozolomide in newly diagnosed glioblastoma, we aim to
      radiologically characterize glioblastoma on therapy until progression and
      investigate whether the type of radiologic progression differs between treatment
      arms and is related to survival and molecular data. Methods: Five progression
      types (PTs) were categorized using an adapted algorithm according to MRI contrast
      enhancement behavior in T1- and T2-weighted images in 621 patients (Bev, n = 299;
      placebo, n = 322). Frequencies of PTs (designated as classic T1, cT1 relapse, T2
      diffuse, T2 circumscribed, and primary nonresponder), time to progression (PFS),
      and overall survival (OS) were assessed within each treatment arm and compared
      with molecular subtypes and O6-methylguanine DNA methyltransferase (MGMT)
      promoter methylation status. Results: PT frequencies differed between the Bev and
      placebo arms, except for "T2 diffuse" (12.4% and 7.1%, respectively). PTs showed
      differences in PFS and OS; with "T2 diffuse" being associated with longest
      survival. Complete disappearance of contrast enhancement during treatment ("cT1
      relapse") showed longer survival than only partial contrast enhancement decrease
      ("classic T1"). "T2 diffuse" was more commonly MGMT hypermethylated. Only weak
      correlations to molecular subtypes from primary tissue were detected.
      Conclusions: Progression of glioblastoma under therapy can be characterized
      radiologically. These radiologic phenotypes are influenced by treatment and
      develop differently over time with differential outcomes. Complete resolution of
      contrast enhancement during treatment is a favorable factor for outcome.

PMID- 29016944
TI  - Auxin Response Dynamics During Wild-Type and entire Flower Development in Tomato.
AB  - The plant hormone auxin is a major regulator of plant development and response to
      environmental cues. Auxin plays a particularly central role in flower
      development, but the knowledge of its role of flower development in crop plants
      with fleshy fruits, such as tomato, is still scarce. Mutations in the Aux/IAA
      gene ENTIRE/Indole Acetic Acid 9 (E/IAA9) lead to the precocious development of
      young gynoecia into parthenocarpic fruits. Here, we compared the distribution of
      the auxin response sensor DR5::VENUS and the auxin efflux transporter PIN1
      between the wild type and entire during successive stages of flower and fruit
      development. Up-regulation of the DR5::VENUS signal in the shoot apical meristem
      (SAM) was observed upon the transition to flowering, implicating a possible role
      for auxin in the transition from a vegetative SAM into an inflorescence meristem.
      DR5::VENUS was expressed in all initiating floral organs. Additionally,
      DR5::VENUS was highly expressed during gametogenesis, in both male and female
      organs, and in the developing seeds during embryogenesis. DR5::VENUS is expressed
      in functional cell layers such as the anther stomium and tapetum, suggesting that
      auxin plays a role in flower organ development and function. The entire mutation
      affected DR5::VENUS expression patterns during inflorescence formation and flower
      organ development, which correlated with phenotypic alterations. We also show
      dynamic distribution and localization of the auxin transporter PIN1 during flower
      and fruit organ development. These results emphasize the dynamic auxin response
      in inflorescence and flower development and suggest multiple roles of auxin in
      these processes.

PMID- 29016945
TI  - FLUCTUATING-LIGHT-ACCLIMATION PROTEIN1, Conserved in Oxygenic Phototrophs,
      Regulates H+ Homeostasis and Non-Photochemical Quenching in Chloroplasts.
AB  - Plants have mechanisms allowing them to acclimate to intense light conditions,
      which involves the dissipation of excess light energy. These mechanisms allow
      plants to perform photosynthesis efficiently and, therefore, must be accurately
      and precisely controlled. However, how plants dissipate excess light energy has
      yet to be fully elucidated. Herein we report the identification of a gene, which
      we named Fluctuating-Light-Acclimation Protein1 (FLAP1), that is conserved in
      oxygenic phototrophs. We show that Arabidopsis FLAP1 is associated with
      chloroplast thylakoid and envelope membranes and that the flap1 mutant shows
      delayed non-photochemical quenching (NPQ) relaxation during induction of
      photosynthesis at moderate light intensity. Under fluctuating light conditions,
      NPQ levels in the flap1 mutant were higher than those in the wild type during the
      high light period, and the mutant exhibited a pale-green phenotype. These
      findings suggest that FLAP1 is involved in NPQ control, which is important for an
      acclimation response to fluctuating light.

PMID- 29016946
TI  - Dissecting Root Proteome Changes Reveals New Insight into Cadmium Stress Response
      in Radish (Raphanus sativus L.).
AB  - Cadmium (Cd) is a widespread heavy metal of particular concern with respect to
      the environment and human health. Although intensive studies have been conducted
      on Cd-exposed transcriptome profiling, little systematic proteome information is
      available on the molecular mechanism of Cd stress response in radish. In this
      study, the radish root proteome under Cd stress was investigated using a
      quantitative multiplexed proteomics approach. Seedlings were grown in nutrient
      solution without Cd (control) or with 10 or 50 MUM CdCl2 for 12 h (Cd10 and Cd50,
      respectively). In total, 91 up- and 66 down-regulated proteins were identified in
      the control vs Cd10 comparison, while 340 up- and 286 down-regulated proteins
      were identified in the control vs Cd50 comparison. Functional annotation
      indicated that these differentially expressed proteins (DEPs) were mainly
      involved in carbohydrate and energy metabolism, stress and defense and signal
      transduction processes. Correlation analysis showed that 33 DEPs matched with
      their transcripts, indicating a relatively low correlation between transcript and
      protein levels under Cd stress. Quantitative real-time PCR evidenced the
      expression patterns of 12 genes encoding their corresponding DEPs. In particular,
      several pivotal proteins associated with carbohydrate metabolism, ROS scavenging,
      cell transport and signal transduction were involved in the coordinated
      regulatory network of the Cd stress response in radish. Root exposure to Cd2+
      activated several key signaling molecules and metal-containing transcription
      factors, and subsequently some Cd-responsive functional genes were mediated to
      reduce Cd toxicity and re-establish redox homeostasis in radish. This is a first
      report on comprehensive proteomic characterization of Cd-exposed root proteomes
      in radish. These findings could facilitate unraveling of the molecular mechanism
      underlying the Cd stress response in radish and provide fundamental insights into
      the development of genetically engineered low-Cd-content radish cultivars.

PMID- 29016948
TI  - Tertiary Care Clinical Experience with Intravenous Lidocaine Infusions for the
      Treatment of Chronic Pain.
AB  - Objective: To evaluate the safety of and long-term pain relief due to intravenous
      lidocaine infusion for the treatment of chronic pain in a tertiary pain
      management clinic. Design: Retrospective chart review. Methods: Medical records
      were reviewed from 233 adult chronic pain patients who underwent one to three
      lidocaine infusions. The initial lidocaine challenge consisted of 1,000 mg/h
      administered intravenously for up to 30 minutes until infusion was complete, full
      pain resolution, the patient requested to stop, side effects (SEs) became
      intolerable, and/or if there were any safety concerns. Subsequent infusions were
      tailored to patient response. Data reviewed included pain diagnosis, lidocaine
      dose, SEs, and duration of pain relief documented at a follow-up visit. Results:
      Patients primarily had neuropathic pain (80%), were 94% white, 58% were female,
      and there was an average pain duration of 7.9 years. SEs were usually mild and
      transient, including perioral tingling, dizziness, tinnitus, and nausea/vomiting,
      and they were uncommon after the initial infusion. Overall, 41% of patients
      showed long-lasting pain relief, with positive response to the initial infusion
      associated with receiving and benefitting from subsequent infusions. Benefit by
      pain diagnoses varied from 32% to 58%. Conclusions: Our retrospective study in a
      heterogeneous population with chronic pain suggests that intravenous lidocaine is
      a safe treatment. Data also suggest long-term pain relief in a significant
      proportion of patients. Additional study is important in order to delineate
      patient selection, determine optimal dosing and treatment frequency, assess pain
      reduction and duration, and treatment cost-effectiveness.

PMID- 29016947
TI  - Visual and semiquantitative 11C-methionine PET: an independent prognostic factor
      for survival of newly diagnosed and treatment-naive gliomas.
AB  - Background: Few data exist regarding the prognostic value of L-[S-methyl
      11C]methionine (MET) PET for treatment-naive gliomas. Methods: A total of 160
      glioma patients (89 men, 71 women; mean age: 45, range 18-84 y) underwent a MET
      PET prior to any therapy. The PET scans were evaluated visually and
      semiquantitatively by tumor-to-background (T/N) ratio thresholds chosen by
      analysis of receiver operating characteristics. Additionally, isocitrate
      dehydrogenase 1-R132H (IDH1-R132H) immunohistochemistry was performed. Survival
      analysis was done using Kaplan-Meier estimates and the Cox proportional hazards
      model. Results: Significantly shorter mean survival times (7.2 vs 8.6 y; P =
      0.024) were seen in patients with amino acid avid gliomas (n = 137) compared with
      visually negative tumors (n = 33) in MET PET. T/N ratio thresholds of 2.1 and 3.5
      were significantly associated with survival (10.3 vs 7 vs 4.3 y; P < 0.001). Mean
      survival differed significantly using the median T/N ratio of 2.4 as cutoff,
      independent of histopathology (P < 0.01; mean survival: 10.2 +/- 0.8 y vs 5.5 +/-
      0.6 y). In the subgroup of 142 glioma patients characterized by IDH1-R132H
      status, METT/N ratio demonstrated a significant prognostic impact in IDH1-R132H
      wildtype astrocytomas and glioblastoma (P = 0.001). Additionally, multivariate
      testing revealed semiquantitative MET PET as an independent prognostic parameter
      for treatment-naive glioma patients without (P = 0.031) and with IDH1-R132H
      characterization of gliomas (P = 0.024; odds ratio 1.57). Conclusion: This
      retrospective analysis demonstrates the value of MET PET as a prognostic
      parameter on survival in treatment-naive glioma patients.

PMID- 29016949
TI  - The MIEL1 E3 Ubiquitin Ligase Negatively Regulates Cuticular Wax Biosynthesis in
      Arabidopsis Stems.

PMID- 29016950
TI  - Hypersensitivity to material and environmental burden as a possible cause of late
      complications of cardiac implantable electronic devices.
AB  - Aims: To evaluate whether patients with late complications of pacemakers or
      implantable cardioverter-defibrillators have hypersensitivity reactions to some
      of the materials used in generators or in electrodes, or to environmental metal
      burden. Methods and results: The cohort consisted of 20 men and 4 women (mean
      age: 62.3 +/- 17.2 years) who had a history of late complications of implanted
      devices. The control group involved 25 men and 8 women (mean age: 64.6 +/- 14.0
      years) who had comparable devices, but no history of late complications.
      Lymphocyte transformation test was used to evaluate hypersensitivity to eight
      metal pollutants (antimony, manganese, mercury, molybdenum, nickel, platinum,
      tin, and titanium) selected by results of questionnaires on environmental burden,
      and by material analysis of generators and electrode surfaces. Exposures to metal
      pollutants were approximately the same in patients and in controls. Titanium
      alloy used in generators contained at least 99.32% of titanium and trace levels
      of other metals; higher levels of tin and platinum were detected in electrode
      surfaces. Hypersensitivity reactions to mercury and tin were significantly more
      frequent in patients than in controls (patients and controls: mercury: 68.2 and
      31.1%, respectively; P = 0.022; tin: 25.0 and 3.2%, respectively; P = 0.035). In
      contrast, hypersensitivity to manganese was significantly more frequent in
      controls than in patients (patients and controls: 13.6 and 50.0%, respectively; P
      = 0.008). Conclusion: Our findings suggest a possible relation between
      hypersensitivity to metals used in implantable devices or to environmental metal
      burden and the occurrence of their late complications.

PMID- 29016952
TI  - Migraine Does Not Affect Pain Intensity Perception: A Cross-Sectional Study.
AB  - Objective: To explore perceived pain intensity (PPI) in three drug-naive patient
      groups characterized by homogeneous migraine phenotypes-migraine without aura
      without cutaneous allodynia (MwoA CA-), MwoA with ictal CA (MwoA CA+), and
      migraine with aura without cutaneous allodynia (MwA CA-)-compared with age- and
      sex-matched healthy controls (HCs). Methods: Using trigeminal heat stimulation
      (THS) at three different predefined intensities (41  degrees C, 51  degrees C,
      and 53  degrees C) performed by the contact heat-evoked potential stimulator
      (CHEPS), PPI was investigated in 34 patients with MwoA CA-, 30 patients with MwoA
      CA+, and 30 patients with MwA CA- compared with 30 age- and sex-matched HCs. The
      patients had never taken migraine-preventive drugs, and they were investigated
      during an interictal period to avoid confounds associated with migraine attack.
      Secondary analyses evaluated associations between PPI and clinical features of
      migraine in patients. Results: No significant differences were observed between
      the four groups for each experimentally induced stimulus. Moreover, no
      significant correlations were found between clinical variables and the PPI of the
      THS at any level of experimental stimulus. Conclusions: Despite the converging
      evidence of pain threshold abnormalities in migraine patients, our findings
      suggest that migraine patients did not exhibit differences in the PPI of THS when
      compared with HCs, independent of phenotype and migraine severity, as well as
      somatic, psychiatric, or pharmacological interferences. This may depend on both
      the nature of the pain stimulus experienced and the involvement of selective
      regions or specific pain processing pathways.

PMID- 29016951
TI  - Compliance with Opioid Therapy: Distinguishing Clinical Characteristics and
      Demographics Among Patients with Cancer Pain.
AB  - Background: Because an increase of patients who misuse opioids has been
      identified in our cancer clinical setting through urine drug testing (UDT) and
      the Screener and Opioid Assessment for Patient's with Pain-Short Form (SOAPP-SF),
      we conducted this retrospective cohort study to identify patient characteristics
      that are associated with UDT that indicates noncompliance. Methods: Over a two
      year period, 167 of 8,727 patients (2.4%) seen in the pain clinic and who
      underwent UDT were evaluated to determine compliance with prescribed opioid
      regimens. Descriptive clinical and demographic data were collected, and group
      differences based on compliance with opioid therapy were evaluated. Results:
      Fifty-eight percent of the patients were noncompliant with their prescribed
      opioid therapy. Noncompliant patients were younger than compliant patients, with
      a median age of 46 vs 49 years (P = 0.0408). Noncompliant patients were more
      likely to have higher morphine equivalent daily doses; however, the difference
      was not statistically significant. Patients with a history of alcohol (ETOH) (P =
      0.0332), illicit drug use (P = 0.1014), and smoking (P = 0.4184) were more likely
      noncompliant. Univariate regression analysis showed that a history of ETOH use (P
      = 0.034), a history of anxiety (P = 0.027), younger age (P = 0.07), and a SOAPP
      SF score of 4 or higher (P = 0.05) were associated with an abnormal UDT.
      Conclusions: History of ETOH use, anxiety, high SOAPP-SF score, and younger age
      were associated with UDT that indicates noncompliance. Given the very small
      percentage of UDT testing, it is quite likely that a significant number of
      patients who did not undergo UDT were also nonadherent with treatment
      recommendations.

PMID- 29016953
TI  - Sleep problems among Chinese clinical nurses working in general hospitals.
AB  - Background: Epidemiological data evaluating sleep problems in clinical nurses in
      mainland China are scarce and an association between sleep problems and
      occupational stress has not been investigated. Aims: To assess the prevalence of
      sleep problems and associated factors and determine their association with
      occupational stress among clinical nurses in general hospitals. Methods: Nurses
      were selected through random cluster sampling. They answered a self-administered
      questionnaire, which included sociodemographic and occupational variables, the
      Pittsburgh Sleep Quality Index (PSQI) scoring system and the Job Content
      Questionnaire for evaluating occupational stress. Logistic regression analysis
      was used to evaluate factors associated with sleep problems. Results: There were
      5012 participants. Mean PSQI score of 4951 subjects included in the final
      analysis was 7.32 +/- 3.24, with 2713 subjects having PSQI >=8, accounting for
      55% of participants. Female subjects in the intensive care unit and emergency
      departments were at higher risk of sleep problems. The following factors also
      presented a risk for sleep problems: multiple years of service, high monthly
      night shift frequency, primary and intermediate professional status, temporary
      employment status and high occupational stressors (including high psychological
      job demands, low job control and low workplace's social support). Conclusions:
      The overall prevalence rate of sleep problems among clinical nurses in general
      hospitals in mainland China was high. Many factors could affect the sleep quality
      of nurses, although occupational stress facilitates development of sleep
      problems. Various risk factors associated with sleep problems among nurses should
      be studied extensively and measures for relieving occupational stress should be
      undertaken.

PMID- 29016954
TI  - Association of Interleukin-6 and Other Cytokines with Self-Reported Pain in
      Prostate Cancer Patients Receiving Chemotherapy.
AB  - Background: Pain is a common and dose-limiting side effect of many potentially
      curative cancer chemotherapeutic agents. This chemotherapy-induced pain (CIP)
      affects the quality of life of cancer patients and survivors and hampers the
      optimal clinical management of chemotherapy in cancer patients. The underlying
      mechanisms remain largely unknown, but changes in levels of cytokines/chemokines
      may contribute to the pathophysiology of CIP. Objective: This retrospective study
      was aimed at examining whether plasma levels of various cytokines change in
      prostate cancer patients after chemotherapy treatment and whether such changes
      (if any) are associated with their pain intensity. Methods: Using a Luminex
      assay, plasma levels of 27 cytokines/chemokines were measured in 78 men: 30
      patients with metastatic prostate cancer who received chemotherapy (Docetaxel, 75
      mg/m2 intravenously), 29 untreated patients with nonmetastatic prostate cancer,
      and 19 healthy controls. Subjective pain was assessed in chemotherapy-treated
      cancer patients using the 11-point numeric rating scale (NRS) pain scores.
      Results: Chemotherapy-treated patients with pain (NRS >= 3) exhibited
      significantly increased levels of the pro-inflammatory cytokines (IL-6, IL-8) and
      chemokines (Eotaxin, VEGF, and IP-10) compared with untreated cancer patients or
      with patients without pain (NRS = 0). Of the 27 cytokines examined, only IL-6 was
      positively correlated with pain intensity in the chemotherapy-treated patients
      with pain. Conclusions: These findings suggest that the cytokines, particularly
      IL-6, whose levels were elevated in the chemotherapy-treated patients may be
      involved in the pathophysiology of CIP, and that they might be potential new
      targets for pain control in cancer patients receiving chemotherapy.

PMID- 29016955
TI  - Is a History of Severe Episodic Low Back Pain an Indicator of a Discogenic
      Etiology?
AB  - Objective: To determine if a history of severe episodic low back pain (LBP)
      correlates with positive discography. Methods: A retrospective chart review
      identified patients undergoing discography from January 2012 through February
      2016. The review determined if the patient's LBP began or continued with severe
      disabling episodes (lasting a minimum of two days). A gradual onset or initiating
      event with continuous symptoms was considered a nonepisodic history. Patients
      were excluded for unclear record, workers' compensation, litigation, prior lumbar
      surgery, radiologic instability, or indeterminate discography. Results: Seventy
      eight patients underwent discography. Thirty-nine patients were included, 31 of
      which had positive discograms. Eight had negative discograms. Nineteen patients
      had a history of episodic LBP, and 20 had no history of episodic LBP. Of those 19
      with a history of episodic LBP, 18 had positive discography and one had negative
      discography. Of those with no history of episodic LBP, 13 had positive
      discography and seven had negative discography. Using the historical finding of
      severe episodic LBP as a test for discogenic source of LBP, the sensitivity is
      58% (95% confidence interval [CI] = 41-75%) and the specificity is 88% (95% CI =
      65-100%). The likelihood ratio is 4.7 (95% CI = 0.72-30). The positive predictive
      value (PPV) is 95% (95% CI = 72-100%). The PPV is based upon a prevalence of 79%
      (discogram positive) in our sample of patients considering fusion surgery. The
      diagnostic confidence odds are 18.2, with a diagnostic confidence of 95%.
      Conclusions: A positive history of severe episodic LBP may be a strong indicator
      for a discogenic etiology.

PMID- 29016956
TI  - Chickpea WRKY70 Regulates the Expression of a Homeodomain-Leucine Zipper (HD-Zip)
      I Transcription Factor CaHDZ12, which Confers Abiotic Stress Tolerance in
      Transgenic Tobacco and Chickpea.
AB  - Drought and salinity are the two major environmental constraints that severely
      affect global agricultural productivity. Plant-specific HD-Zip transcription
      factors are involved in plant growth, development and stress responses. In the
      present study, we explored the functional characteristics and regulation of a
      novel HD-Zip (I) gene from chickpea, CaHDZ12, in response to water-deficit and
      salt-stress conditions. Transgenic tobacco lines over-expressing CaHDZ12
      exhibited improved tolerance to osmotic stresses and increased sensitivity to
      abscisic acid (ABA). Physiological compatibility of transgenic lines was found to
      be more robust compared to the wild-type plants under drought and salinity
      stress. Additionally, expression of several stress-responsive genes was
      significantly induced in CaHDZ12 transgenic plants. On the other hand, silencing
      of CaHDZ12 in chickpea resulted in increased sensitivity to salt and drought
      stresses. Analysis of different promoter deletion mutants identified CaWRKY70
      transcription factor as a transcriptional regulator of CaHDZ12 expression. In
      vivo and in vitro interaction studies detected an association between CaWRKY70
      and CaHDZ12 promoter during stress responses. Epigenetic modifications underlying
      histone acetylation at the CaHDZ12 promoter region play a significant role in
      stress-induced activation of this gene. Collectively, our study describes a
      crucial and unique mechanistic link between two distinct transcription factors in
      regulating plant adaptive stress response.

PMID- 29016957
TI  - Case-specific colleague guidance for general practitioners' management of
      sickness absence.
AB  - Background: General practitioners (GPs) report sickness absence certification as
      challenging. They express need for support with functional assessment beyond
      guidelines and reforms. Case-specific collegial one-to-one guidance for other
      clinical topics has proved popular with GPs and may be an acceptable and
      effective way to improve GPs skills and competence in sickness absence
      certification. Aims: To present a new model of case-specific colleague guidance
      focusing on the management of long-term sickness absence and to describe its
      feasibility in terms of application and reception among GPs, and also GPs' self
      reports of effects on their practice. Methods: Randomly selected GPs received
      case-specific collegial guidance over a 12-month period, in two Norwegian trials,
      delivered by former GPs employed by the social security administration. We
      measured reception and perceived effects by GPs' self-report and registered
      participation and withdrawal rates. Results: The participation rate (n = 165) was
      94%, and no GPs withdrew during training. Among the 116 GPs responding to the
      survey (70%), 112 (97%; 95% CI 92-99) stated they would recommend it to their
      colleagues. Considerable benefit from the guidance was reported by 68 (59%; 95%
      CI 50-68). The GPs self-reported other effects on their sickness absence
      certification, specifically an increased use of part-time sickness absence (Fit
      Note equivalent). Conclusions: This model of case-specific colleague guidance to
      aid GPs' management of long-term sickness absence is feasible and was popular.
      This type of guidance was perceived by GPs to be somewhat beneficial and to alter
      their sickness absence certification behaviour, though the true impact requires
      further testing in controlled trials.

PMID- 29016958
TI  - Increased Central Nervous System Interleukin-8 in a Majority Postlaminectomy
      Syndrome Chronic Pain Population.
AB  - Background and Objectives: Multiple processes have been identified as potential
      contributors to chronic pain, with increasing evidence illustrating an
      association with aberrant levels of neuroimmune mediators. The primary objectives
      of the present study were to examine central nervous system cytokines,
      chemokines, and growth factors present in a chronic pain population and to
      explore patterns of the same mediator molecules over time. Secondary objectives
      explored the relationship of central and peripheral neuroimmune mediators while
      examining the levels of anxiety, depression, sleep quality, and perception of
      pain associated with the chronic pain patient experience. Methods: Cerebrospinal
      fluid (CSF) from a population of majority postlaminectomy syndrome patients (N =
      8) was compared with control CSF samples (N = 30) to assess for significant
      differences in 10 cytokines, chemokines, and growth factors. The patient
      population was then followed over time, analyzing CSF, plasma, and
      psychobehavioral measures. Results: The present observational study is the first
      to demonstrate increased mean CSF levels of interleukin-8 (IL-8; P < 0.001) in a
      small population of majority postlaminectomy syndrome patients, as compared with
      a control population. Over time in pain patients, CSF levels of IL-8 increased
      significantly (P < 0.001). Conclusions: These data indicate that IL-8 should be
      further investigated and psychobehavioral components considered in the overall
      chronic pain paradigm. Future studies examining the interactions between these
      factors and IL-8 may identify novel targets for treatment of persistent pain
      states.

PMID- 29016959
TI  - Low-Boron Tolerance Strategies Involving Pectin-Mediated Cell Wall Mechanical
      Properties in Brassica napus.
AB  - Boron (B) is an essential micronutrient for the growth and development of plants.
      Oilseed rape (Brassica napus L.) is a staple oleaginous crop, which is greatly
      susceptible to B deficiency. Significant differences in tolerance of low-B
      stresses are observed in rapeseed genotypes, but the underlying mechanism remains
      unclear, particularly at the single-cell level. Here we provide novel insights
      into pectin-mediated cell wall (CW) mechanical properties implicated in the
      differential tolerance of low B in rapeseed genotypes. Under B deficiency,
      suspension cells of the low-B-sensitive genotype 'W10' showed more severely
      deformed morphology, lower viabilities and a more easily ruptured CW than those
      of the low-B-tolerant genotype 'QY10'. Cell rupture was attributed to the
      weakened CW mechanical strength detected by atomic force microscopy; the CW
      mechanical strength of 'QY10' was reduced by 13.6 and 17.4%, whereas that of
      'W10' was reduced by 29.0 and 30.4% under 0.25 and 0.10 MUM B conditions,
      respectively. The mechanical strength differences between 'QY10' and 'W10' were
      diminished after the removal of pectin. Further, 'W10' exhibited significantly
      higher pectin concentrations with much more rhamnogalacturonan II (RG-II)
      monomer, and also presented obviously higher mRNA abundances of pectin
      biosynthesis-related genes than 'QY10' under B deficiency. CW regeneration was
      more difficult for protoplasts of 'W10' than for those of 'QY10'. Taking the
      results together, we conclude that the variations in pectin-endowed CW mechanical
      properties play key roles in modulating the differential genotypic tolerance of
      rapeseed to low-B stresses at both the single-cell and the plant level, and this
      can potentially be used as a selection trait for low-B-tolerant rapeseed
      breeding.

PMID- 29016960
TI  - Validation of the HCM Risk-SCD model in patients with hypertrophic cardiomyopathy
      following alcohol septal ablation.
AB  - Aims: The HCM Risk-SCD model for prediction of sudden cardiac death (SCD) in
      hypertrophic cardiomyopathy recommended by the 2014 European Society of
      Cardiology (ESC) guidelines has not been validated after septal reduction
      therapy. The aim of this study was to validate the HCM Risk-SCD model in patients
      undergoing alcohol septal ablation (ASA) and to compare its performance to
      previous models. Methods and result: A total of 844 ASA patients without prior
      SCD event were included. The primary endpoint was a composite of SCD and
      appropriate implantable cardioverter defibrillator (ICD) therapy, identical to
      the HCM Risk-SCD endpoint. A distinction between periprocedural (<=30 days) and
      long-term (>30 days) SCD was made to discern procedure-related adverse arrhythmic
      events caused by the ASA-induced myocardial infarction from long-term SCD risk.
      Twenty patients reached the SCD endpoint within the first 30 days. During a
      follow-up of 6.5 +/- 4.2 years, another 46 patients reached the SCD endpoint. The
      predicted 5-year SCD risk according to the HCM Risk-SCD model was 5.1%, and the
      observed 5-year SCD risk was 4.0%. The C-statistics for the use of the HCM Risk
      SCD model was 0.61 (P = 0.02), the C-statistics for the use of the 2003 American
      College of Cardiology/ESC guidelines was 0.59 (P = 0.051), and the C-statistic
      for the use of the 2011 American College of Cardiology Foundation/American Heart
      Association guidelines was 0.58 (P = 0.054). Maximal left ventricular wall
      thickness, syncope after ASA, and fulfilling the 2014 ESC recommendations for
      primary ICD implantation according to the HCM Risk-SCD model, respectively,
      predicted SCD during long-term follow-up. Conclusion: The HCM Risk-SCD model can
      be used for SCD prediction in patients undergoing ASA.

PMID- 29016961
TI  - Apple RING E3 ligase MdMIEL1 inhibits anthocyanin accumulation by ubiquitinating
      and degrading MdMYB1 protein.
AB  - MdMYB1 is an important regulator for anthocyanin accumulation in apple (Malus *
      domestica). Here, an apple RING E3 ligase, MdMIEL1, was screened out as a partner
      of MdMYB1 with a yeast two-hybrid approach. Pull-down, bimolecular fluorescence
      complementation and coimmunoprecipitation assays further verified the interaction
      between MdMIEL1 and MdMYB1 proteins. Subsequently, in vitro and in vivo
      experiments indicated that MdMIEL1 functioned as a ubiquitin E3 ligase to
      ubiquitinate MdMYB1 protein, followed by degradation through a 26S proteasome
      pathway. Furthermore, transgenic studies in apple calli and Arabidopsis
      demonstrated that MdMIEL1 negatively regulated anthocyanin accumulation by
      modulating the degradation of MdMYB1 protein. Taken together, our findings
      provide a new insight into the molecular mechanism by which MdMIEL1 negatively
      regulates anthocyanin biosynthesis by ubiquitinating and degrading MdMYB1
      protein.

PMID- 29016962
TI  - An Apple Protein Kinase MdSnRK1.1 Interacts with MdCAIP1 to Regulate ABA
      Sensitivity.
AB  - ABA is a crucial phytohormone for development and stress responses in plants.
      Snf1-related protein kinase 1.1 (SnRK1.1) is involved in the ABA response.
      However, the molecular mechanism underlying the SnRK1.1 response to ABA is
      largely unknown. Here, it was found that overexpression of the apple MdSnRK1.1
      gene enhanced ABA sensitivity in both transgenic apple calli and Arabidopsis
      seedlings. Subsequently, a yeast two-hybrid screen demonstrated that MdCAIP1 (C2
      domain ABA Insensitive Protein1) interacted with MdSnRK1.1. Their interaction was
      further confirmed by pull-down and co-immunoprecipitation assays. Expression of
      the MdCAIP1 gene was positively induced by ABA. Its overexpression enhanced ABA
      sensitivity in transgenic apple calli. Furthermore, it was found that MdSnRK1.1
      phosphorylated the MdCAIP1 protein in vivo and promoted its degradation in vitro
      and in vivo. As a result, MdSnRK1.1 inhibited MdCAIP1-mediated ABA sensitivity,
      and MdCAIP1 partially reduced MdSnRK1.1-mediated ABA sensitivity. Our findings
      indicate that MdSnRK1.1 plays an important role in the ABA response, partially by
      controlling the stability of the MdCAIP1 protein.

PMID- 29016963
TI  - Risks and Benefits of Ceasing or Continuing Anticoagulant Medication for Image
      Guided Procedures for Spine Pain: A Systematic Review.
AB  - Objective: To determine the risks of continuing or ceasing anticoagulant or
      antiplatelet medications prior to image-guided procedures for spine pain. Design:
      Systematic review of the literature with comprehensive analysis of the published
      data. Interventions: Following a search of the literature for studies pertaining
      to spine pain interventions in patients on anticoagulant medication, seven
      reviewers appraised the studies identified and assessed the quality of evidence
      presented. Outcome Measures: Evidence was sought regarding risks associated with
      either continuing or ceasing anticoagulant and antiplatelet medication in
      patients having image-guided interventional spine procedures. The evidence was
      evaluated in accordance with the Grades of Recommendation, Assessment,
      Development, and Evaluation system. Results: From a source of 120 potentially
      relevant articles, 14 provided applicable evidence. Procedures involving
      interlaminar access carry a nonzero risk of hemorrhagic complications, regardless
      of whether anticoagulants are ceased or continued. For other procedures,
      hemorrhagic complications have not been reported, and case series indicate that
      they are safe when performed in patients who continue anticoagulants. Three
      articles reported the adverse effects of ceasing anticoagulants, with serious
      consequences, including death. Conclusions: Other than for interlaminar
      procedures, the evidence does not support the view that anticoagulant and
      antiplatelet medication must be ceased before image-guided spine pain procedures.
      Meanwhile, the evidence shows that ceasing anticoagulants carries a risk of
      serious consequences, including death. Guidelines on the use of anticoagulants
      should reflect these opposing bodies of evidence.

PMID- 29016964
TI  - Light Quality Affects Chloroplast Electron Transport Rates Estimated from Chl
      Fluorescence Measurements.
AB  - Chl fluorescence has been used widely to calculate photosynthetic electron
      transport rates. Portable photosynthesis instruments allow for combined
      measurements of gas exchange and Chl fluorescence. We analyzed the influence of
      spectral quality of actinic light on Chl fluorescence and the calculated electron
      transport rate, and compared this with photosynthetic rates measured by gas
      exchange in the absence of photorespiration. In blue actinic light, the electron
      transport rate calculated from Chl fluorescence overestimated the true rate by
      nearly a factor of two, whereas there was closer agreement under red light. This
      was consistent with the prediction made with a multilayer leaf model using
      profiles of light absorption and photosynthetic capacity. Caution is needed when
      interpreting combined measurements of Chl fluorescence and gas exchange, such as
      the calculation of CO2 partial pressure in leaf chloroplasts.

PMID- 29016966
TI  - Review of Factors, Methods, and Outcome Definition in Designing Opioid Abuse
      Predictive Models.
AB  - Objective: Several opioid risk assessment tools are available to prescribers to
      evaluate opioid analgesic abuse among chronic patients. The objectives of this
      study are to 1) identify variables available in the literature to predict opioid
      abuse; 2) explore and compare methods (population, database, and analysis) used
      to develop statistical models that predict opioid abuse; and 3) understand how
      outcomes were defined in each statistical model predicting opioid abuse. Design:
      The OVID database was searched for this study. The search was limited to articles
      written in English and published from January 1990 to April 2016. This search
      generated 1,409 articles. Only seven studies and nine models met our inclusion
      exclusion criteria. Results: We found nine models and identified 75 distinct
      variables. Three studies used administrative claims data, and four studies used
      electronic health record data. The majority, four out of seven articles (six out
      of nine models), were primarily dependent on the presence or absence of opioid
      abuse or dependence (ICD-9 diagnosis code) to define opioid abuse. However, two
      articles used a predefined list of opioid-related aberrant behaviors.
      Conclusions: We identified variables used to predict opioid abuse from electronic
      health records and administrative data. Medication variables are the recurrent
      variables in the articles reviewed (33 variables). Age and gender are the most
      consistent demographic variables in predicting opioid abuse. Overall, there is
      similarity in the sampling method and inclusion/exclusion criteria (age, number
      of prescriptions, follow-up period, and data analysis methods). Intuitive
      research to utilize unstructured data may increase opioid abuse models' accuracy.

PMID- 29016965
TI  - TaPUB1, a Putative E3 Ligase Gene from Wheat, Enhances Salt Stress Tolerance in
      Transgenic Nicotiana benthamiana.
AB  - High salinity is one of the most severe environmental stresses and limits the
      growth and yield of diverse crop plants. We isolated a gene named TaPUB1 from
      wheat (Triticum aestivum L. cv HF9703) that encodes a novel protein containing a
      U-box domain, the precursor RNA processing 19p (Prp19) superfamily and WD-40
      repeats. Real-time reverse transcription-PCR analysis showed that TaPUB1
      transcript accumulation was up-regulated by high salinity, drought and
      phytohormones, suggesting that it plays a role in the abiotic-related defense
      response. We overexpressed TaPUB1 in Nicotiana benthamiana to evaluate the
      function of TaPUB1 in the regulation of the salt stress response. Transgenic N.
      benthamiana plants (OE) with constitutively overexpressed TaPUB1 under the
      control of the Cauliflower mosaic virus 35S (CaMV 35S) promoter exhibited a
      higher germination rate, less growth inhibition, less Chl loss and higher
      photosynthetic capacity than wild-type (WT) plants under salt stress conditions.
      These results demonstrated the increased tolerance of OE plants to salt stress
      compared with the WT. The OE plants had lower osmotic potential (OP), reduced Na+
      toxicity and less reactive oxygen species accumulation compared with the WT,
      which may be related to their higher level of osmolytes, lower Na+/K+ ratio and
      higher antioxidant enzyme activities under salt stress conditions. Consistent
      with these results, the up-regulated expression of osmic- and antioxidant-related
      genes in OE plants indicated a role for TaPUB1 in plant salt tolerance.

PMID- 29016967
TI  - Automatable algorithms to identify nonmedical opioid use using electronic data: a
      systematic review.
AB  - Objective: Improved methods to identify nonmedical opioid use can help direct
      health care resources to individuals who need them. Automated algorithms that use
      large databases of electronic health care claims or records for surveillance are
      a potential means to achieve this goal. In this systematic review, we reviewed
      the utility, attempts at validation, and application of such algorithms to detect
      nonmedical opioid use. Materials and Methods: We searched PubMed and Embase for
      articles describing automatable algorithms that used electronic health care
      claims or records to identify patients or prescribers with likely nonmedical
      opioid use. We assessed algorithm development, validation, and performance
      characteristics and the settings where they were applied. Study variability
      precluded a meta-analysis. Results: Of 15 included algorithms, 10 targeted
      patients, 2 targeted providers, 2 targeted both, and 1 identified medications
      with high abuse potential. Most patient-focused algorithms (67%) used
      prescription drug claims and/or medical claims, with diagnosis codes of substance
      abuse and/or dependence as the reference standard. Eleven algorithms were
      developed via regression modeling. Four used natural language processing, data
      mining, audit analysis, or factor analysis. Discussion: Automated algorithms can
      facilitate population-level surveillance. However, there is no true gold standard
      for determining nonmedical opioid use. Users must recognize the implications of
      identifying false positives and, conversely, false negatives. Few algorithms have
      been applied in real-world settings. Conclusion: Automated algorithms may
      facilitate identification of patients and/or providers most likely to need more
      intensive screening and/or intervention for nonmedical opioid use. Additional
      implementation research in real-world settings would clarify their utility.

PMID- 29016968
TI  - Formalizing drug indications on the road to therapeutic intent.
AB  - Therapeutic intent, the reason behind the choice of a therapy and the context in
      which a given approach should be used, is an important aspect of medical
      practice. There are unmet needs with respect to current electronic mapping of
      drug indications. For example, the active ingredient sildenafil has 2 distinct
      indications, which differ solely on dosage strength. In progressing toward a
      practice of precision medicine, there is a need to capture and structure
      therapeutic intent for computational reuse, thus enabling more sophisticated
      decision-support tools and a possible mechanism for computer-aided drug
      repurposing. The indications for drugs, such as those expressed in the Structured
      Product Labels approved by the US Food and Drug Administration, appears to be a
      tractable area for developing an application ontology of therapeutic intent.

PMID- 29016969
TI  - Implementation of a scalable, web-based, automated clinical decision support risk
      prediction tool for chronic kidney disease using C-CDA and application
      programming interfaces.
AB  - Background and Objective: Clinical decision support tools for risk prediction are
      readily available, but typically require workflow interruptions and manual data
      entry so are rarely used. Due to new data interoperability standards for
      electronic health records (EHRs), other options are available. As a clinical case
      study, we sought to build a scalable, web-based system that would automate
      calculation of kidney failure risk and display clinical decision support to users
      in primary care practices. Materials and Methods: We developed a single-page
      application, web server, database, and application programming interface to
      calculate and display kidney failure risk. Data were extracted from the EHR using
      the Consolidated Clinical Document Architecture interoperability standard for
      Continuity of Care Documents (CCDs). EHR users were presented with a
      noninterruptive alert on the patient's summary screen and a hyperlink to details
      and recommendations provided through a web application. Clinic schedules and CCDs
      were retrieved using existing application programming interfaces to the EHR, and
      we provided a clinical decision support hyperlink to the EHR as a service.
      Results: We debugged a series of terminology and technical issues. The
      application was validated with data from 255 patients and subsequently deployed
      to 10 primary care clinics where, over the course of 1 year, 569 533 CCD
      documents were processed. Conclusions: We validated the use of interoperable
      documents and open-source components to develop a low-cost tool for automated
      clinical decision support. Since Consolidated Clinical Document Architecture
      based data extraction extends to any certified EHR, this demonstrates a
      successful modular approach to clinical decision support.

PMID- 29016971
TI  - Efficiency and safety of speech recognition for documentation in the electronic
      health record.
AB  - Objective: To compare the efficiency and safety of using speech recognition (SR)
      assisted clinical documentation within an electronic health record (EHR) system
      with use of keyboard and mouse (KBM). Methods: Thirty-five emergency department
      clinicians undertook randomly allocated clinical documentation tasks using KBM or
      SR on a commercial EHR system. Tasks were simple or complex, and with or without
      interruption. Outcome measures included task completion times and observed
      errors. Errors were classed by their potential for patient harm. Error causes
      were classified as due to IT system/system integration, user interaction,
      comprehension, or as typographical. User-related errors could be by either
      omission or commission. Results: Mean task completion times were 18.11% slower
      overall when using SR compared to KBM (P = .001), 16.95% slower for simple tasks
      (P = .050), and 18.40% slower for complex tasks (P = .009). Increased errors were
      observed with use of SR (KBM 32, SR 138) for both simple (KBM 9, SR 75; P <
      0.001) and complex (KBM 23, SR 63; P < 0.001) tasks. Interruptions did not
      significantly affect task completion times or error rates for either modality.
      Discussion: For clinical documentation, SR was slower and increased the risk of
      documentation errors, including errors with the potential to cause clinical harm
      compared to KBM. Some of the observed increase in errors may be due to suboptimal
      SR to EHR integration and workflow. Conclusion: Use of SR to drive interactive
      clinical documentation in the EHR requires careful evaluation. Current generation
      implementations may require significant development before they are safe and
      effective. Improving system integration and workflow, as well as SR accuracy and
      user-focused error correction strategies, may improve SR performance.

PMID- 29016970
TI  - A genome-by-environment interaction classifier for precision medicine: personal
      transcriptome response to rhinovirus identifies children prone to asthma
      exacerbations.
AB  - Objective: To introduce a disease prognosis framework enabled by a robust
      classification scheme derived from patient-specific transcriptomic response to
      stimulation. Materials and Methods: Within an illustrative case study to predict
      asthma exacerbation, we designed a stimulation assay that reveals individualized
      transcriptomic response to human rhinovirus. Gene expression from peripheral
      blood mononuclear cells was quantified from 23 pediatric asthmatic patients and
      stimulated in vitro with human rhinovirus. Responses were obtained via the single
      subject gene set testing methodology "N-of-1-pathways." The classifier was
      trained on a related independent training dataset (n = 19). Novel visualizations
      of personal transcriptomic responses are provided. Results: Of the 23 pediatric
      asthmatic patients, 12 experienced recurrent exacerbations. Our classifier, using
      individualized responses and trained on an independent dataset, obtained 74%
      accuracy (area under the receiver operating curve of 71%; 2-sided P = .039).
      Conventional classifiers using messenger RNA (mRNA) expression within the viral
      exposed samples were unsuccessful (all patients predicted to have recurrent
      exacerbations; accuracy of 52%). Discussion: Prognosis based on single time
      point, static mRNA expression alone neglects the importance of dynamic genome-by
      environment interplay in phenotypic presentation. Individualized transcriptomic
      response quantified at the pathway (gene sets) level reveals interpretable
      signals related to clinical outcomes. Conclusion: The proposed framework provides
      an innovative approach to precision medicine. We show that quantifying personal
      pathway-level transcriptomic response to a disease-relevant environmental
      challenge predicts disease progression. This genome-by-environment interaction
      assay offers a noninvasive opportunity to translate omics data to clinical
      practice by improving the ability to predict disease exacerbation and increasing
      the potential to produce more effective treatment decisions.

PMID- 29016973
TI  - Electronic health record adoption in US hospitals: the emergence of a digital
      "advanced use" divide.
AB  - Objective: While most hospitals have adopted electronic health records (EHRs), we
      know little about whether hospitals use EHRs in advanced ways that are critical
      to improving outcomes, and whether hospitals with fewer resources - small, rural,
      safety-net - are keeping up. Materials and Methods: Using 2008-2015 American
      Hospital Association Information Technology Supplement survey data, we measured
      "basic" and "comprehensive" EHR adoption among hospitals to provide the latest
      national numbers. We then used new supplement questions to assess advanced use of
      EHRs and EHR data for performance measurement and patient engagement functions.
      To assess a digital "advanced use" divide, we ran logistic regression models to
      identify hospital characteristics associated with high adoption in each advanced
      use domain. Results: We found that 80.5% of hospitals adopted at least a basic
      EHR system, a 5.3 percentage point increase from 2014. Only 37.5% of hospitals
      adopted at least 8 (of 10) EHR data for performance measurement functions, and
      41.7% of hospitals adopted at least 8 (of 10) patient engagement functions.
      Critical access hospitals were less likely to have adopted at least 8 performance
      measurement functions (odds ratio [OR] = 0.58; P < .001) and at least 8 patient
      engagement functions (OR = 0.68; P = 0.02). Discussion: While the Health
      Information Technology for Economic and Clinical Health Act resulted in
      widespread hospital EHR adoption, use of advanced EHR functions lags and a
      digital divide appears to be emerging, with critical-access hospitals in
      particular lagging behind. This is concerning, because EHR-enabled performance
      measurement and patient engagement are key contributors to improving hospital
      performance. Conclusion: Hospital EHR adoption is widespread and many hospitals
      are using EHRs to support performance measurement and patient engagement.
      However, this is not happening across all hospitals.

PMID- 29016972
TI  - Biases introduced by filtering electronic health records for patients with
      "complete data".
AB  - Objective: One promise of nationwide adoption of electronic health records (EHRs)
      is the availability of data for large-scale clinical research studies. However,
      because the same patient could be treated at multiple health care institutions,
      data from only a single site might not contain the complete medical history for
      that patient, meaning that critical events could be missing. In this study, we
      evaluate how simple heuristic checks for data "completeness" affect the number of
      patients in the resulting cohort and introduce potential biases. Materials and
      Methods: We began with a set of 16 filters that check for the presence of
      demographics, laboratory tests, and other types of data, and then systematically
      applied all 216 possible combinations of these filters to the EHR data for 12
      million patients at 7 health care systems and a separate payor claims database of
      7 million members. Results: EHR data showed considerable variability in data
      completeness across sites and high correlation between data types. For example,
      the fraction of patients with diagnoses increased from 35.0% in all patients to
      90.9% in those with at least 1 medication. An unrelated claims dataset
      independently showed that most filters select members who are older and more
      likely female and can eliminate large portions of the population whose data are
      actually complete. Discussion and Conclusion: As investigators design studies,
      they need to balance their confidence in the completeness of the data with the
      effects of placing requirements on the data on the resulting patient cohort.

PMID- 29016975
TI  - JAMIA is going green.

PMID- 29016974
TI  - Blockchain distributed ledger technologies for biomedical and health care
      applications.
AB  - Objectives: To introduce blockchain technologies, including their benefits,
      pitfalls, and the latest applications, to the biomedical and health care domains.
      Target Audience: Biomedical and health care informatics researchers who would
      like to learn about blockchain technologies and their applications in the
      biomedical/health care domains. Scope: The covered topics include: (1)
      introduction to the famous Bitcoin crypto-currency and the underlying blockchain
      technology; (2) features of blockchain; (3) review of alternative blockchain
      technologies; (4) emerging nonfinancial distributed ledger technologies and
      applications; (5) benefits of blockchain for biomedical/health care applications
      when compared to traditional distributed databases; (6) overview of the latest
      biomedical/health care applications of blockchain technologies; and (7)
      discussion of the potential challenges and proposed solutions of adopting
      blockchain technologies in biomedical/health care domains.

PMID- 29016976
TI  - A description of familial clustering of meningiomas in the Utah population.
AB  - Background: Meningiomas are common intracranial tumors in adults, yet the
      genetics and cause of sporadic meningiomas are not well understood. Few familial
      clusters have been reported. The aim of this study was to investigate the
      familiality of meningiomas within the Utah Population Database. Methods:
      Meningioma cases reported in the Utah Cancer Registry were identified. Relative
      risk of their relatives was calculated. All possible cases were assessed with the
      Genealogical Index of Familiality (GIF), which measures average pairwise
      relatedness of all possible pairs using the Malecot coefficient of kinship.
      Clusters of cases descending from a common ancestor were identified. Results:
      Eight hundred fifty-eight meningioma cases were reported. The relative risk of a
      first- or second-degree relative was 3.13 (95% CI: 1.67, 5.36) or 2.28 (1.30,
      3.70), respectively. The GIF statistic demonstrated a clear excess of
      relationships for genetic distance <4 (closer than first cousins). We identified
      920 pedigrees, including 2-21 meningioma cases. One hundred eighty-nine of these
      pedigrees, including 2-15 cases, had a significant excess (P < 0.05) of
      meningioma cases over what was expected. Conclusions: This Utah population-based
      analysis of meningiomas shows clear evidence of familial clustering and supports
      both a familial and a germline variant basis for meningioma. These clusters may
      allow identification of genes likely to contribute to tumorigenesis in high-risk
      pedigrees. These relative risk data provide the basis for further investigations
      of genetic contributions to meningioma. These data may contribute to developing a
      basis for determining screening criteria of higher-risk pedigrees for the
      presence of meningiomas.

PMID- 29016977
TI  - Transcription Factor AsMYC2 Controls the Jasmonate-Responsive Expression of ASS1
      Regulating Sesquiterpene Biosynthesis in Aquilaria sinensis (Lour.) Gilg.
AB  - Sesquiterpenes are one of the most important defensive secondary metabolite
      components of agarwood. Agarwood, which is a product of the Aquilaria sinensis
      response to external damage, is a fragrant and resinous wood that is widely used
      in traditional medicines, incense and perfume. We previously reported that
      jasmonic acid (JA) plays an important role in promoting agarwood sesquiterpene
      biosynthesis and induces expression of the sesquiterpene synthase ASS1, which is
      a key enzyme that is responsible for the biosynthesis of agarwood sesquiterpenes
      in A. sinensis. However, little is known about this molecular regulation
      mechanism. Here, we characterized a basic helix-loop-helix transcription factor,
      AsMYC2, from A. sinensis as an activator of ASS1 expression. AsMYC2 is an
      immediate-early jasmonate-responsive gene and is co-induced with ASS1. Using a
      combination of yeast one-hybrid assays and chromatin immunoprecipitation
      analyses, we showed that AsMYC2 bound the promoter of ASS1 containing a G-box
      motif. AsMYC2 activated expression of ASS1 in tobacco epidermis cells and up
      regulated expression of sesquiterpene synthase genes (TPS21 and TPS11) in
      Arabidopsis, which was also promoted by methyl jasmonate. Our results suggest
      that AsMYC2 participates in the regulation of agarwood sesquiterpene biosynthesis
      in A. sinensis by controlling the expression of ASS1 through the JA signaling
      pathway.

PMID- 29016978
TI  - Comparative proteomic analyses of two Taxus species (Taxus * media and Taxus
      mairei) reveals variations in the metabolisms associated with paclitaxel and
      other metabolites.
AB  - Taxus species are well-known for paclitaxel, which exhibits antitumor activities
      and is used for treating various cancers. Although most Taxus species are
      widespread in many areas, few studies have characterized the variation in
      metabolism among different Taxus species. Using an integrated approach involving
      'tandem mass tag' labeling and liquid chromatography-tandem mass spectrometry
      (HPLC-MS), proteomes of T. media and T. mairei were investigated and 4078
      proteins were quantified. Screening and classification of differentially
      expressed proteins revealed many metabolism-associated proteins. In detail, four
      enzymes involved in the flavonoid biosynthesis pathway were predominantly
      expressed in T. mairei. Four enzymes associated with supplying precursors for
      paclitaxel biosynthesis and three cytochrome P450 taxoid oxygenases were
      preferentially expressed in T. media compared with T. mairei. Furthermore,
      variations in taxoid contents between T. media and T. mairei were determined
      using HPLC-MS analysis. Variations in flavonoid contents between T. media and T.
      mairei were determined by HPLC analysis. A number of differentially expressed
      proteins may provide an explanation for the variation in metabolisms of different
      Taxus species.

PMID- 29016979
TI  - Attention-mediated neurocognitive profiles in survivors of pediatric brain
      tumors: comparison to children with neurodevelopmental ADHD.
AB  - Background: Attention and working memory symptoms are among the most common late
      effects in survivors of pediatric brain tumors, and are often associated with
      academic and psychosocial difficulties. Diagnostic and treatment approaches
      derived from the literature on attention-deficit hyperactivity disorder (ADHD)
      have frequently been applied to survivors, yet the extent of overlap in cognitive
      profiles between these groups is unclear. The objective of the present study is
      to compare neurocognition in survivors of brain tumors and children with
      neurodevelopmental ADHD. Methods: Neuropsychological data were abstracted from
      clinically referred brain tumor survivors (n = 105, Mage = 12.0 y, 52.4% male)
      and children with ADHD (n = 178, Mage = 11.1 y, 64.0% male). Data consist of a
      battery of parent-report questionnaires and performance-based neuropsychological
      measures. Results: Twenty-five survivors (23.8%) of pediatric brain tumors met
      symptom criteria for ADHD. Participants with neurodevelopmental ADHD and
      survivors who met ADHD criteria had significantly greater parent- (P < 0.001) and
      teacher-reported (P < 0.001) working memory and behavior regulation difficulties
      than survivors of tumor who did not meet criteria. Children with ADHD symptoms
      also performed worse on measures of sustained attention than survivors without
      ADHD symptoms (P < 0.001). Additionally, survivors with ADHD symptoms had greater
      performance-based working memory difficulties than either survivors without
      attention problems or children with neurodevelopmental ADHD (P = 0.002).
      Conclusions: Nearly a quarter of survivors with attention symptoms have
      functional profiles that are similar to children with neurodevelopmental ADHD.
      They also experience more neurocognitive impairments than survivors without
      attentional difficulties, particularly in working memory. Screening for ADHD
      symptoms may help providers triage a subset of individuals in need of earlier or
      additional neuropsychological assessment.

PMID- 29016980
TI  - Effectiveness and Cost-effectiveness of Opportunistic Screening and Stepped-care
      Interventions for Older Alcohol Users in Primary Care.
AB  - Aims: To compare the clinical effectiveness and cost-effectiveness of a stepped
      care intervention versus a minimal intervention for the treatment of older
      hazardous alcohol users in primary care. Method: Multi-centre, pragmatic RCT, set
      in Primary Care in UK. Patients aged >= 55 years scoring >= 8 on the Alcohol Use
      Disorders Identification Test were allocated either to 5-min of brief advice or
      to 'Stepped Care': an initial 20-min of behavioural change counselling, with Step
      2 being three sessions of Motivational Enhancement Therapy and Step 3 referral to
      local alcohol services (progression between each Step being determined by
      outcomes 1 month after each Step). Outcome measures included average drinks per
      day, AUDIT-C, alcohol-related problems using the Drinking Problems Index, health
      related quality of life using the Short Form 12, costs measured from a
      NHS/Personal Social Care perspective and estimated health gains in quality
      adjusted life-years measured assessed EQ-5D. Results: Both groups reduced alcohol
      consumption at 12 months but the difference between groups was small and not
      significant. No significant differences were observed between the groups on
      secondary outcomes. In economic terms stepped care was less costly and more
      effective than the minimal intervention. Conclusions: Stepped care does not
      confer an advantage over a minimal intervention in terms of reduction in alcohol
      use for older hazardous alcohol users in primary care. However, stepped care has
      a greater probability of being more cost-effective. Trial Registration: Current
      controlled trials ISRCTN52557360. Short summary: A stepped care approach was
      compared with brief intervention for older at-risk drinkers attending primary
      care. While consumption reduced in both groups over 12 months there was no
      significant difference between the groups. An economic analysis indicated the
      stepped care which had a greater probability of being more cost-effective than
      brief intervention.

PMID- 29016983
TI  - Predictors of sleep disordered breathing in children: the PANIC study.
AB  - Objective: We studied longitudinally the associations of craniofacial morphology,
      mouth breathing, orthodontic treatment, and body fat content with the risk of
      having and developing sleep disordered breathing (SDB) in childhood. We
      hypothesized that deviant craniofacial morphology, mouth breathing, and adiposity
      predict SDB among children. Materials and methods: The participants were 412
      children 6-8 years of age examined at baseline and 329 children aged 9-11 years
      re-examined at an average 2.2-year follow-up. An experienced orthodontist
      evaluated facial proportions, dental occlusion, soft tissue structures, and mode
      of breathing and registered malocclusions in orthodontic treatment. Body fat
      percentage was assessed by dual-energy X-ray absorptiometry and SDB symptoms by a
      questionnaire. Results: Children with SDB more likely had convex facial profile,
      increased lower facial height, mandibular retrusion, tonsillar hypertrophy, and
      mouth breathing at baseline and convex facial profile, mandibular retrusion, and
      mouth breathing at follow-up than children without SDB at these examinations.
      Male gender and body adiposity, mouth breathing, and distal molar occlusion at
      baseline were associated with SDB later in childhood. Adipose tissue under the
      chin, mandibular retrusion, vertically large or normal throat and malocclusion in
      orthodontic treatment at baseline predicted developing SDB during follow-up of
      among children without SDB at baseline. Limitations: We could not conduct
      polysomnographic examinations to define sleep disturbances. Instead, we used a
      questionnaire filled out by the parents to assess symptoms of SDB. Conclusions:
      The results indicate that among children, deviant craniofacial morphology, mouth
      breathing, body adiposity, and male gender seem to have implications in the
      pathophysiology of SDB.

PMID- 29016984
TI  - How Classical Conditioning Shapes Placebo Analgesia: Hidden versus Open
      Conditioning.
AB  - Objective: To investigate the influence of expectancy of pain intensity, fear of
      pain (trait), and fear (state) on the effectiveness of hidden and open
      conditioning to produce placebo analgesia. Methods: A total of 90 healthy female
      volunteers were randomly assigned to three groups (hidden conditioning, open
      conditioning, and control) that received electrical stimuli preceded by either
      orange or blue lights. One color was paired with painful stimuli (control
      stimuli) and the other color was paired with nonpainful stimuli (conditioned
      stimuli) in both the hidden and open conditioning groups. Only participants in
      the open conditioning group were informed about this association. In the control
      group, both color lights were followed by control stimuli. In the testing phase,
      both colored lights were followed by identical control stimuli. Participants
      rated pain intensity, expectancy of pain intensity, fear, and fear of pain.
      Results: A significant analgesic effect was found only in the hidden conditioning
      group, where no explicit verbal suggestions were provided. Hidden conditioning
      had an effect on expectancy and fear-participants in the hidden conditioning
      group expected less pain and experienced less fear in relation to conditioned
      stimuli. Fear was the only predictor of placebo analgesia in the hidden
      conditioning group. Neither expectancy of pain intensity nor fear of pain
      predicted placebo analgesia. Conclusions: Fear seems to be a more important
      factor than expectancy in producing placebo analgesia induced by hidden
      conditioning.

PMID- 29016985
TI  - The effect of various adhesives, enamel etching, and base treatment on the
      failure frequency of customized lingual brackets: a randomized clinical trial.
AB  - Objectives: The aim of this paper was to compare failure differences in precious
      metal customized lingual brackets bonded with three adhesive systems. Also,
      differences in failure of non-precious metal brackets with and without a
      silicatized base layer bonded with the same adhesive, as well as the influence of
      enamel etching prior to using a self-etching dual cure resin were explored.
      Materials/methods: Five different groups were defined in a semi-randomized
      approach. Group 1 (IME): Maxcem Elite with 378 Incognito brackets and etched
      teeth, Group 2 (IMNE): Maxcem Elite with 193 Incognito brackets on non-etched
      teeth, Group 3 (INE): Nexus+Excite with 385 Incognito brackets, Group 4 (IRE):
      Relyx with 162 Incognito brackets, Group 5 (HRME) and Group 6 (HNRME): Maxcem
      Elite with 182 Harmony brackets with silicatized and non-slicatized bases
      respectively. Bracket failures were recorded over a 12-month period. Results: The
      number of failures during the observation period was small in the various
      adhesives types of groups, as well as in HRME and HNRME groups, and the
      comparisons among those groups were non-significant (P > 0.05). A statistically
      significant difference (P < 0.05) was found between the IME and IMNE groups.
      Conclusions: 1. During the first year of treatment customized lingual brackets
      failure frequencies (rates) are not different for the three adhesive materials
      tested. 2. Eliminating the etching stage when using self-etch/self-adhesive
      adhesives, may lead to a dramatic increase in the failure rates. 3. Silicoating
      of stainless steel customized lingual brackets does not seem to influence the
      failure of the bonds.

PMID- 29016982
TI  - Burnout in Belgian physicians and nurses.
AB  - Background: Burnout in healthcare is a worldwide problem. However, most studies
      focus narrowly on work-related factors and outcomes in one health profession or
      speciality. Aims: To investigate the prevalence of burnout and its association
      with job demands, job resources, individual well-being, work-related attitudes
      and behaviour in physicians and nurses across different specialties. Methods:
      Multi-centre cross-sectional study of physicians and nurses working in Belgian
      hospitals. An electronic questionnaire was used to assess job demands (e.g.
      workload), job resources (e.g. autonomy) and indicators of well-being, work
      related attitudes and behaviours. Structural equation modelling was used to
      examine interrelationships between explanatory variables and outcomes. Results:
      1169 physicians and 4531 nurses participated; response rate 26%. High scores
      (>75th percentile in reference group of Dutch health care workers) were seen in
      6% of the sample on three burnout dimensions (i.e. emotional exhaustion,
      depersonalization and personal competence) and in 13% for at least two
      dimensions. In contrast to the other dimensions, emotional exhaustion strongly
      related to almost all variables examined in the model. Positive associations were
      seen with workload, role conflicts, emotional burden and work-home interference
      and negative associations with learning and development opportunities and co
      worker support. Emotional exhaustion correlated negatively with well-being,
      turnover intention, being prepared and able to work until retirement age,
      medication use, absenteeism and presenteeism. Conclusions: Work-related factors
      were critical correlates of emotional exhaustion, which strongly related to poor
      health and turnover intention. Randomized controlled trials are suggested to
      underpin the effectiveness of interventions tackling job stressors and promoting
      job resources.

PMID- 29016981
TI  - Prevalence of Polysubstance Abuse and Dual Diagnosis in Patients Admitted to
      Alcohol Rehabilitation Units for Alcohol-Related Problems in Italy: Changes in 15
      Years.
AB  - Aims: Alcohol abuse has long been known as a disease with social and economic
      burden to society. Given the complex nature of alcohol treatment, it is
      worthwhile to examine the change over time of patients admitted to residential
      alcohol abuse rehabilitation units. Methods: The data were collected from two
      Italian projects on alcoholics performed in the mid-1990s (ASSALT) and in 2009
      (CORRAL), respectively. Categorical variables were considered in terms of
      absolute and relative frequencies. Comparisons of relative frequencies between
      groups were assessed by means of Fisher's exact test. Mixed logistic regression
      models were fitted to CORRAL data to identify the predictors of the probability
      of being a polysubstance abuser or having a dual diagnosis. The association
      estimates were reported as adjusted odds ratios and relative 95% confidence
      intervals. Results: Compared to the mid-1990s, in 2009 patients were older (P=
      0.0003), with a higher level of education (P= 0.0204), with fewer comorbidities
      (liver disease except cirrhosis, P < 0.0001; polyneuropathy, P= 0.0001), more
      frequently polysubstance abusers (P < 0.0001), affected by dual diagnosis (P <
      0.0001). In 2009, the probability of being a polysubstance abuser was higher in
      younger and in patients with dual psychiatric diagnosis. Female gender and
      polysubstance abuse were positively associated to the probability of being
      affected by dual psychiatric diagnosis. Conclusions: The increment of patients
      admitted to residential programs for alcohol dependence with polysubstance abuse
      and/or dual psychiatric diagnoses suggests the need to pay more attention to both
      psychological/psychiatric interventions and internal medicine/physical
      rehabilitation. Short summary: The results of this study suggest that further
      research is needed to identify the best treatment strategy that is safe and
      effective for the new population of alcoholics.

PMID- 29016986
TI  - Retained pacemaker and implantable cardioverter-defibrillator components after
      heart transplantation are common and may lead to adverse events.
AB  - Aims: Many patients have a cardiac implantable electronic device (CIED) extracted
      at the time of heart transplantation. CIED components may be retained after heart
      transplantation, but their frequency, nature, and clinical significance is
      uncertain. Methods and results: Consecutive patients that underwent heart
      transplantation over 10 years from 1 January 2007 until 1 January 2017 were
      identified from the unit database. Pre- and post-operative chest radiographs were
      reviewed by two independent observers for the presence of CIED components.
      Adverse events relating to any retained CIED component were recorded. Two hundred
      and six patients had a CIED removed at the time of transplantation. Retained CIED
      components were present in 86 (42%) patients. The most common retained CIED
      components were suture sleeves and superior vena cava (SVC) coils of dual coil
      implantable cardioverter-defibrillator (ICD) leads. An SVC coil was retained in
      25% of patients that had a dual coil ICD lead. Seven adverse events were
      associated with CIED removal or retained CIED components, including one fatal
      event. However, retained CIED components were not associated with reduced long
      term survival after heart transplantation. Conclusion: Retained CIED components
      were seen in 42% of patients that had a CIED prior to transplantation, may be
      associated with serious adverse events but are not associated with reduced long
      term survival. Cardiac surgeons should be aware of all CIED system components and
      be familiar with techniques for their complete removal at the time of
      transplantation.

PMID- 29016988
TI  - The Path to Thioredoxin and Redox Regulation Beyond Chloroplasts.
AB  - Once the ferredoxin/thioredoxin system was established as a mechanism linking
      light to the post-translational regulation of chloroplast enzymes, I considered
      that plants might harbor a light-independent mechanism utilizing this same enzyme
      chemistry based on thiol-disulfide redox transitions. After reflection, it
      occurred to me that such a mechanism could be fundamental to seeds of cereals
      that undergo dramatic change following exposure to oxygen during maturation and
      drying. The pursuit of this idea led to the discovery of a family of
      extraplastidic thioredoxins, designated the h-type, that resemble animal and
      bacterial counterparts in undergoing enzymatic reduction with NADPH. Current
      evidence suggests that h-type thioredoxins function broadly throughout the plant.
      Here I describe how the thioredoxin h field developed, its current status and
      potential for contributing material benefits to society.

PMID- 29016989
TI  - The influence of progression of atrial fibrillation on quality of life: a report
      from the Euro Heart Survey.
AB  - Aims: Progression of atrial fibrillation (AF) from paroxysmal to persistent forms
      is an active field of research. The influence of AF progression on health related
      quality of life (HRQoL) is currently unknown. We aimed to assess the influence of
      AF progression on HRQoL, and whether this association is mediated through
      symptoms, treatment, and major adverse events. Methods and results: In the Euro
      Heart Survey, 967 patients were included with paroxysmal AF who filled out
      EuroQoL-5D at baseline and at 1 year follow-up. Those who progressed (n = 132,
      13.6%) developed more problems during follow-up than those who did not, on all
      EuroQoL-5D domains (increase in problems on mobility 20.5% vs. 11.4%; self-care
      12.9% vs. 6.2%; usual activities 23.5% vs. 14.0%; pain/discomfort 20.5% vs.
      13.7%; and anxiety/depression 22.7% vs. 15.7%; all P < 0.05), leading to a
      decrease in utility [baseline 0.744 +/- 0.26, follow-up 0.674 +/- 0.36;
      difference -0.07 (95% CI [-0.126,-0.013], P = 0.02)]. Multivariate analysis
      showed that the effect of progression on utility is mediated by a large effect of
      adverse events [stroke (-0.27 (95% CI [-0.43,-0.11]); P = 0.001], heart failure [
      0.12 (95% CI [-0.20,-0.05]); P = 0.001], malignancy (-0.31 (95% CI [-0.56,
      0.05]); P = 0.02] or implantation of an implantable cardiac defibrillator [-0.12
      (95% CI [-0.23,-0.02]); P = 0.03)], as well as symptomatic AF [-0.04 (95% CI [
      0.08,-0.01]); P = 0.008]. Conclusion: AF progression is associated with a
      decrease in HRQoL. However, multivariate analysis revealed that AF progression
      itself does not have a negative effect on HRQoL, but that this effect can be
      attributed to a minor effect of the associated symptoms and a major effect of
      associated adverse events.

PMID- 29016990
TI  - Age and sex differences in atrial fibrosis among patients with atrial
      fibrillation.
AB  - Aim: Age and female sex are associated with a higher risk of stroke in atrial
      fibrillation (AF). We sought to determine whether advancing age and female sex
      are associated with higher atrial fibrosis. Methods and results : We conducted an
      observational cohort study of patients with AF enrolled in the University of Utah
      AF Database and a non-AF control group who underwent late-gadolinium enhancement
      magnetic resonance imaging (LGE-MRI) for atrial fibrosis quantification.
      Participants with contra-indications for contrast MRI scanning were excluded.
      Nine hundred and eight consecutive men and women with AF and 15 non-AF controls
      were included in this study. Left atrial fibrosis increased with age in both men
      and women with AF. Women with AF (n = 316) were older than men (n = 592): mean
      age 68.7+/-11.6 vs. 64.9+/-11.7 years; P < 0.01, and had higher left atrial
      fibrosis compared with men 17.5 +/- 10.1% vs. 15.3 +/- 8.9%; P < 0.001. Women
      also had a higher prevalence of prior stroke compared with men (15.8% vs. 6.5%; P
      < 0.001). Age and sex relationships with atrial fibrosis remained significant in
      multivariate analysis. Compared with the non-AF control group, patients with AF
      had significantly higher atrial fibrosis: 16.0 +/- 9.4 vs. 5.5 +/- 5.8%; P <
      0.001. Conclusions: Advancing age and female sex are associated with a higher
      burden of atrial fibrosis in patients with AF. Women with a prior history of
      stroke also have higher fibrosis compared with both women and men without history
      of stroke. Advanced fibrosis may explain the female and age association with
      stroke in AF.

PMID- 29016987
TI  - Long-term exposure to ambient air pollution and incidence of brain tumor: the
      European Study of Cohorts for Air Pollution Effects (ESCAPE).
AB  - Background: Epidemiological evidence on the association between ambient air
      pollution and brain tumor risk is sparse and inconsistent. Methods: In 12 cohorts
      from 6 European countries, individual estimates of annual mean air pollution
      levels at the baseline residence were estimated by standardized land-use
      regression models developed within the ESCAPE and TRANSPHORM projects:
      particulate matter (PM) <=2.5, <=10, and 2.5-10 MUm in diameter (PM2.5, PM10, and
      PMcoarse), PM2.5 absorbance, nitrogen oxides (NO2 and NOx) and elemental
      composition of PM. We estimated cohort-specific associations of air pollutant
      concentrations and traffic intensity with total, malignant, and nonmalignant
      brain tumor, in separate Cox regression models, adjusting for risk factors, and
      pooled cohort-specific estimates using random-effects meta-analyses. Results: Of
      282194 subjects from 12 cohorts, 466 developed malignant brain tumors during 12
      years of follow-up. Six of the cohorts also had data on nonmalignant brain tumor,
      where among 106786 subjects, 366 developed brain tumor: 176 nonmalignant and 190
      malignant. We found a positive, statistically nonsignificant association between
      malignant brain tumor and PM2.5 absorbance (hazard ratio and 95% CI: 1.67; 0.89
      3.14 per 10-5/m3), and weak positive or null associations with the other
      pollutants. Hazard ratio for PM2.5 absorbance (1.01; 0.38-2.71 per 10-5/m3) and
      all other pollutants were lower for nonmalignant than for malignant brain tumors.
      Conclusion: We found suggestive evidence of an association between long-term
      exposure to PM2.5 absorbance indicating traffic-related air pollution and
      malignant brain tumors, and no association with overall or nonmalignant brain
      tumors.

PMID- 29016991
TI  - Case report of asthma associated with 3D printing.
AB  - Background: Three-dimensional (3D) printing is being increasingly used in
      manufacturing and by small business entrepreneurs and home hobbyists. Exposure to
      airborne emissions during 3D printing raises the issue of whether there may be
      adverse health effects associated with these emissions. Aims: We present a case
      of a worker who developed asthma while using 3D printers, which illustrates that
      respiratory problems may be associated with 3D printer emissions. Case report:
      The patient was a 28-year-old self-employed businessman with a past history of
      asthma in childhood, which had resolved completely by the age of eight. He
      started using 10 fused deposition modelling 3D printers with acrylonitrile
      butadiene-styrene filaments in a small work area of approximately 3000 cubic
      feet. Ten days later, he began to experience recurrent chest tightness, shortness
      of breath and coughing at work. After 3 months, his work environment was modified
      by reducing the number of printers, changing to polylactic acid filaments and
      using an air purifier with an high-efficiency particulate air filter and organic
      cartridge. His symptoms improved gradually, although he still needed periodic
      treatment with a salbutamol inhaler. While still symptomatic, a methacholine
      challenge indicated a provocation concentration causing a 20% fall in FEV1 (PC20)
      of 4 mg/ml, consistent with mild asthma. Eventually, his symptoms resolved
      completely and a second methacholine challenge after symptom resolution was
      normal (PC20 > 16 mg/ml). Conclusions: This case indicates that workers may
      develop respiratory problems, including asthma when using 3D printers. Further
      investigation of the specific airborne emissions and health problems from 3D
      printing is warranted.

PMID- 29016992
TI  - How to prevent atrial oesophageal fistula following ablation of atrial
      fibrillation: are there actually any effective methods?-Authors' reply.

PMID- 29016993
TI  - A Positron Emission Tomography Study of Norepinephrine Transporter Occupancy and
      Its Correlation with Symptom Response in Depressed Patients Treated with
      Quetiapine XR.
AB  - Background: Quetiapine is effective in treating depressive symptoms in major
      depressive disorder and bipolar disorder, but the mechanisms underlying its
      antidepressants effects are unknown. Norquetiapine, a metabolite of quetiapine,
      has high affinity for norepinephrine transporter, which might account for its
      therapeutic efficacy. Methods: In this study, we used positron emission
      tomography with (S,S)-[11C]O-methyl reboxetine to estimate norepinephrine
      transporter density and assess the relationship between norepinephrine
      transporter occupancy by quetiapine XR and improvement in depression in patients
      with major depressive disorder (n=5) and bipolar disorder (n=5). After the
      baseline positron emission tomography scan, patients were treated with quetiapine
      XR with a target dose of 150 mg in major depressive disorder and 300 mg in
      bipolar disorder. Patients had a second positron emission tomography scan at the
      end of week 2 and a final scan at week 7. Results: Norepinephrine transporter
      density was significantly lower in locus ceruleus in patients compared with
      healthy subjects. Further, there was a significant positive correlation between
      quetiapine XR dose and norepinephrine transporter occupancy in locus ceruleus at
      week 2. The norepinephrine transporter occupancy at week 2 in hypothalamus but
      not in other regions predicted improvement in depression as reflected by
      reduction in MADRS scores from baseline to week 7. The estimated dose of
      quetiapine XR associated with 50% norepinephrine transporter occupancy in
      hypothalamus at week 2 was 256 mg and the estimated plasma levels of
      norquetiapine to achieve 50% norepinephrine transporter occupancy was 36.8 ug/L.
      Conclusion: These data provide preliminary support for the hypothesis that
      norepinephrine transporter occupancy by norquetiapine may be a contributor to the
      antidepressant effects of quetiapine.

PMID- 29016994
TI  - Neuromodulation in Postherpetic Neuralgia: Case Reports and Review of the
      Literature.
AB  - Objective: Postherpetic neuralgia (PHN) is common in the United States. Current
      treatment options for PHN are fairly limited. Spinal cord stimulation (SCS) and
      peripheral nerve stimulation (PNS) are considered mostly experimental and still
      rarely performed in patients with PHN. Design: Two case reports and a review of
      the literature. Setting: Tertiary academic medical center. Methods: 1) Pubmed,
      Ovid, and EBMR databases were searched for all reports that had the following key
      words: postherpetic neuralgia, spinal cord stimulation, and peripheral nerve
      stimulation. 2) A retrospective chart review was performed for all the patients
      that underwent PNS for PHN at Mayo Clinic Florida (MCF). Results: There were 20
      original reports that described 309 patients with PHN who were treated with SCS.
      Sixteen reports had a permanent implantation of SCS, with a total of 255
      patients, out of which 120 had long-term pain relief. There were six reports of
      subcutaneous PNS for PHN (in a thoracic area). Four reports provided data on
      success rates where all five patients received complete pain relief. In our
      practice, two patients underwent subcutaneous PNS for PHN (in the thoracic area)
      with good pain relief for 10 months and 2.5 years, respectively. Conclusions:
      Based on our review of the literature and the two cases at MCF, subcutaneous PNS
      seems to be a promising intervention in the treatment of PHN.

PMID- 29016996
TI  - Identification of time-to-peak on dynamic 18F-FET-PET as a prognostic marker
      specifically in IDH1/2 mutant diffuse astrocytoma.
AB  - Background: Stratification of glioma according to isocitrate dehydrogenase 1/2
      (IDH1/2) mutation and 1p/19q codeletion status has gained major importance in the
      new World Health Organization (WHO) classification. Parameters derived from
      uptake dynamics of 18F-fluoro-ethyl-tyrosine PET (18F-FET-PET) such as minimal
      time-to-peak (TTPmin) allow discrimination between different prognostic glioma
      subgroups, too. The present study is aimed at exploring whether TTPmin analysis
      provides prognostic information beyond the WHO classification. Methods: Three
      hundred patients with newly diagnosed WHO 2007 grades II-IV gliomas with 18F-FET
      PET imaging at diagnosis were grouped into 4 subgroups (IDH1/2 mut-1p/19q codel;
      IDH1/2 mut-1p/19q non-codel; IDH1/2 wildtype WHO grade II and III tumors; and
      glioblastoma). Clinical and imaging factors such as age, Karnofsky performance
      score, treatment, TTPmin, and maximal tumor-to-brain ratio (TBRmax) were analyzed
      with regard to progression-free and overall survival (PFS and OS) via univariate
      and multivariate regression analysis. Results: PFS and OS were longest in the
      IDH1/2 mut-1p/19q codel subgroup, followed by IDH1/2 mut-1p/19q non-codel, IDH1/2
      wildtype, and GBM (P < 0.001). Further, outcome stratified by TTPmin with a
      cutoff of 17.5 minutes revealed significantly longer PFS and OS in patients with
      TTPmin >17.5 minutes (P < 0.001 for PFS and OS). Lower TBRmax values or the
      absence of 18F-FET uptake was also associated with favorable outcome in the
      entire group. In the subgroup analyses, longer median TTPmin was associated with
      improved outcome specifically in the IDH1/2 mut-1p/19q non-codel group.
      Conclusion: 18F-FET-PET-derived dynamic analysis defines prognostically distinct
      subgroups of IDH1/2 mutant-1p/19q non-codel gliomas which cannot be distinguished
      as yet by molecular marker analysis.

PMID- 29016997
TI  - The Influence of a Cryptochrome on the Gene Expression Profile in the Diatom
      Phaeodactylum tricornutum under Blue Light and in Darkness.
AB  - Diatoms, albeit being only distantly related with higher plants, harbor a plant
      like cryptochrome (CryP) that was proposed to act as a photoreceptor required for
      the regulation of some photosynthetic proteins. Plant cryptochromes are involved
      in the regulation of developmental processes relevant only to multicellular
      organisms. Their role in the unicellular diatoms to date is mostly enigmatic. To
      elucidate the function of this plant-like cryptochrome in a unicellular species,
      we examined the role of CryP in the regulation of transcription in the diatom
      Phaeodactylum tricornutum by comparative RNA-seq of wild type and CryP knock-down
      mutants, under prolonged darkness and one hour after onset of blue light. In
      total, mRNAs of 12,298 genes were identified and more than 70% of the genes could
      be sorted into functional bins. CryP influenced groups of transcripts in three
      different ways: some transcripts displayed altered expression under blue light
      only, others independent of the light condition, and, surprisingly, some were
      influenced by CryP only in darkness. Genes regulated in any condition were
      distributed over almost all functional categories. CryP exerted an influence on
      two other photoreceptors: the genes encoding phytochrome and CPF1, another
      cryptochrome, which were down-regulated by CryP independent of the light
      condition. However, the regulatory responses of the affected photoreceptors on
      transcriptional output were independent. The influence of CryP on the expression
      of other photoreceptors hints to the existence of a regulatory signaling network
      in diatoms that includes several cryptochromes and phytochrome, whereby CryP acts
      as a regulator of transcript abundance under light as well as in darkness.

PMID- 29016995
TI  - Ultra-Brief Mindfulness Training Reduces Alcohol Consumption in At-Risk Drinkers:
      A Randomized Double-Blind Active-Controlled Experiment.
AB  - Background: Like other complex psychosocial interventions, mindfulness-based
      treatments comprise various modality-specific components as well as nonspecific
      therapeutic ingredients that collectively contribute to efficacy. Consequently,
      the isolated effects of mindfulness strategies per se remain unclear. Methods:
      Using a randomized double-blind design, we compared the isolated effects of 11
      minutes of "supervised" mindfulness instruction against a closely matched active
      control (relaxation) on subjective, physiological, and behavioral indices of
      maladaptive alcohol responding in drinkers at risk of harm from alcohol use (n =
      68). Simple follow-up instructions on strategy use were provided, but practice
      was unsupervised and not formally monitored. Results: Both groups showed acute
      reductions in craving after training, although a trend group x time interaction
      (P = .056) suggested that this reduction was greater in the relaxation group (d =
      0.722 P < .001) compared with the mindfulness group (d = 0.317, P = .004).
      Furthermore, upregulation of parasympathetic activity was found after relaxation
      (d = 0.562; P < .001) but not mindfulness instructions (d = 0.08; P > .1; group x
      time interaction: P = .009). By contrast, only the mindfulness group showed a
      reduction in past-week alcohol consumption at 7-day follow-up (-9.31 units, d =
      0.593, P < .001), whereas no significant reduction was seen in the relaxation
      group (-3.00 units, d = 0.268, P > .1; group x time interaction: P = .026).
      Conclusion: Very brief mindfulness practice can significantly reduce alcohol
      consumption among at-risk drinkers, even with minimal encouragement to use this
      strategy outside of the experimental context. The effects on consumption may
      therefore represent a lower bound of efficacy of "ultra-brief" mindfulness
      instructions in hazardous drinkers, at least at short follow-up intervals.

PMID- 29016999
TI  - The Space of Okada with Bilateral Facet Joint Arthrograms During a Lumbar
      Interlaminar Epidural Injection.

PMID- 29016998
TI  - Phase II study of cabozantinib in patients with progressive glioblastoma: subset
      analysis of patients naive to antiangiogenic therapy.
AB  - Background: Cabozantinib is a tyrosine kinase inhibitor with activity against
      vascular endothelial growth factor receptor 2 (VEGFR2) and MET that has
      demonstrated clinical activity in advanced solid tumors. This open-label, phase
      II trial evaluated cabozantinib in patients with recurrent or refractory
      glioblastoma (GBM). Methods: Patients were initially enrolled at a starting dose
      of 140 mg/day, but the starting dose was amended to 100 mg/day because of
      toxicity. Treatment continued until disease progression or unacceptable toxicity.
      The primary endpoint was objective response rate assessed by an independent
      radiology facility using modified Response Assessment in Neuro-Oncology criteria.
      Additional endpoints included duration of response, 6-month and median
      progression-free survival, overall survival, and safety. Results: Among 152
      patients naive to prior antiangiogenic therapy, the objective response rate was
      17.6% and 14.5% in the 140 mg/day and 100 mg/day groups, respectively, which did
      not meet the predefined statistical target for success. The proportions of
      patients alive and progression free at 6 months were 22.3% and 27.8%,
      respectively. Median progression-free survival was 3.7 months in both groups, and
      median overall survival was 7.7 months and 10.4 months, respectively. The
      incidence of grade 3/4 adverse events (AEs) was 79.4% and 84.7% in the 140 mg/day
      and 100 mg/day groups, respectively, and dose reductions due to AEs were
      experienced by 61.8% and 72.0%, respectively. Common grade 3/4 AEs included
      fatigue, diarrhea, and palmar-plantar erythrodysesthesia syndrome. Conclusions:
      Cabozantinib showed evidence of clinical activity in patients with recurrent GBM
      naive to antiangiogenic therapy, although the predefined statistical target for
      success was not met. At the starting doses assessed, AEs were frequently managed
      with dose reductions. Clinical Trials Registration Number: NCT00704288
      (https://www.clinicaltrials.gov/ct2/show/NCT00704288).

PMID- 29017000
TI  - Visual and Postural Motion-Evoked Dizziness Symptoms Are Predominant in
      Vestibular Migraine Patients.
AB  - Background: Vestibular migraine (VM) is one of the most common underdiagnosed
      disorders. We aimed to study the clinical characteristics of VM patients who were
      referred to a neurology-headache unit by otolaryngology after exclusion of
      peripheral causes of vertigo. Methods: One hundred and one patients diagnosed
      with VM in the headache unit were included. Description of vestibular symptoms,
      demographic and clinical features, trigger factors, accompanying diseases, and
      response to vestibular-suppressant medications and prophylactic migraine
      treatment were evaluated. Results: Vestibular symptoms were triggered by daily
      head and body movements and mainly consisted of brief attacks lasting seconds
      (60.4% of patients) although the total duration of the vestibular episode lasted
      hours or days. Other aggravating factors were moving visual stimuli, passive
      motion, and visually busy environments. Visually induced vestibular symptoms were
      defined by 71.3% of the patients, and positional motion-induced vestibular
      symptoms were described by 82.2% of the patients. Vestibular symptoms were mainly
      defined as feeling the ground slipping from under their feet (40.6%), feeling
      like there is an earthquake or swaying (27.7%), sensation of rocking on a boat
      (26.7%), and sensation as if stepping on empty space (24.8%). The majority of the
      patients (83.2%) previously used vestibular-suppressant drugs, and these drugs
      were effective temporarily only in 12.9%. Conclusions: Chronic recurrent
      dizziness symptoms, rather than internal or external vertigo, are predominant in
      our VM patients. Recurrent brief dizziness attacks induced upon routine visual
      and/or postural motion, longstanding symptoms with limited response to vestibular
      suppressants, and precipitation by typical migraine triggers are suggestive of
      VM.

PMID- 29017002
TI  - The question mark sign of large vessel vasculitis on 18F-FDG PET/CT.

PMID- 29017001
TI  - Single-Pixel Densitometry Revealed the Presence of Peptidoglycan in the
      Intermembrane Space of the Moss Chloroplast Envelope in Conventional Electron
      Micrographs.
AB  - Chloroplasts are believed to be descendants of ancestral cyanobacteria that have
      a peptidoglycan layer between the outer and the inner membranes. In particular,
      cyanelles having peptidoglycan in Cyanophora paradoxa are considered as evidence
      for the endosymbiotic origin of chloroplasts. The moss Physcomitrella patens has
      a complete set of genes involved in the synthesis of peptidoglycan, but a
      peptidoglycan layer has not been observed by conventional electron microscopy to
      date. Recently, a new metabolic labeling technique using a fluorescent probe was
      applied to visualize putative peptidoglycan surrounding the chloroplasts. The
      exact localization of the peptidoglycan, however, has not been clearly
      identified. Here we examined conventional electron micrographs of two types of
      moss materials (mutants or ampicillin-treated plants), one presumably having
      peptidoglycan and the other presumably lacking peptidoglycan, and analyzed in
      detail, by single-pixel densitometry, the electron density of the chloroplast
      envelope membranes and the intermembrane space. Statistical analysis showed that
      the relative electron density within the intermembrane space with respect to that
      of the envelope membranes was significantly higher in the materials presumably
      having peptidoglycan than in the materials presumably devoid of peptidoglycan. We
      consider this difference as bona fide evidence for the presence of peptidoglycan
      between the outer and the inner envelope membranes in the wild-type chloroplasts
      of the moss, although its density is lower than that in bacteria and cyanelles.
      We will also discuss this low-density peptidoglycan in the light of the
      phylogenetic origin of peptidoglycan biosynthesis enzymes.

PMID- 29017003
TI  - MYC5 is Involved in Jasmonate-Regulated Plant Growth, Leaf Senescence and Defense
      Responses.
AB  - Jasmonates (JAs), lipid-derived phytohormones, regulate plant growth, development
      and defenses against biotic stresses. CORONATINE INSENSITIVE1 perceives bioactive
      JA and recruits JASMONATE ZIM-DOMAIN (JAZ) proteins for ubiquitination and
      subsequent degradation via the 26S proteasome, which de-represses JAZ-targeted
      transcription factors that regulate diverse JA responses. Recent studies showed
      that the Arabidopsis basic helix-loop-helix transcription factor MYC5 interacts
      with JAZs and regulates stamen development. However, whether MYC5 mediates other
      JA responses is unclear. Here, we show that MYC5 functions redundantly with MYC2,
      MYC3 and MYC4 to modulate JA-regulated root growth inhibition and plant defenses
      against insect attack and pathogen infection, and that it positively regulates JA
      induced leaf senescence. Our findings define MYC5 as an important regulator that
      is essential for diverse JA responses.

PMID- 29017004
TI  - Eating frequency predicts changes in regional body fat distribution in healthy
      adults.
AB  - Background: Eating frequency (EF) has been associated with generalized obesity.
      Aim: We aimed to prospectively investigate potential associations of frequency of
      eating episodes with regional fat layers. Design: EF was evaluated at baseline in
      115 subjects free of clinically overt cardiovascular disease (54 +/- 9.1 years,
      70 women) in a prospective, observational study. Methods: Metabolic parameters
      known to be associated with dietary factors and anthropometric markers including
      ultrasound assessment of subcutaneous (Smin) and pre-peritoneal (Pmax) fat and
      their ratio Smin/Pmax (AFI) were evaluated at baseline and at follow-up, 5 years
      later. Results: EF at baseline positively correlated with Pmax, even after
      adjustment for potential confounders. EF above median was also an independent
      predictor for Pmax (beta coefficient = -0.192, P = 0.037) and AFI (beta
      coefficient = 0.199, P = 0.049) at follow up. Multivariable linear mixed models
      analysis demonstrated that subjects with increased EF presented a lower
      progression rate of Pmax (beta = -0.452, P = 0.006) and a higher progression rate
      of AFI (beta = 0.563, P = 0.003) over time, independently of age, sex,
      progression of BMI, energy intake, smoking and changes in parameters of glucose
      metabolism. Conclusions: High EF is associated with lower progression rate of pre
      peritoneal fat accumulation. Future interventional studies should further
      investigate the clinical utility of these findings.

PMID- 29017005
TI  - Early planned removal of umbilical venous catheters to prevent infection in
      newborn infants.
AB  - BACKGROUND: Lengthy duration of use may be a risk factor for umbilical venous
      catheter-associated bloodstream infection in newborn infants. Early planned
      removal of umbilical venous catheters (UVCs) is recommended to reduce the
      incidence of infection and associated morbidity and mortality. OBJECTIVES: To
      compare the effectiveness of early planned removal of UVCs (up to two weeks after
      insertion) versus an expectant approach or a longer fixed duration in preventing
      bloodstream infection and other complications in newborn infants.To perform
      subgroup analyses by gestational age at birth and prespecified planned duration
      of UVC placement (see "Subgroup analysis and investigation of heterogeneity").
      SEARCH METHODS: We used the standard Cochrane Neonatal search strategy including
      electronic searches of the Cochrane Central Register of Controlled Trials
      (CENTRAL; 2017, Issue 4), Ovid MEDLINE, Embase, and the Maternity & Infant Care
      Database (until May 2017), as well as conference proceedings and previous
      reviews. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials
      that compared effects of early planned removal of UVCs (up to two weeks after
      insertion) versus an expectant approach or a longer fixed duration in preventing
      bloodstream infection and other complications in newborn infants. DATA COLLECTION
      AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and
      independently undertook data extraction. We analysed treatment effects and
      reported risk ratio (RR) and risk difference (RD) for dichotomous data, and mean
      difference (MD) for continuous data, with respective 95% confidence intervals
      (CIs). We planned to use a fixed-effect model in meta-analyses and to explore
      potential causes of heterogeneity in sensitivity analyses. We assessed the
      quality of evidence for the main comparison at the outcome level using GRADE
      methods. MAIN RESULTS: We found one eligible trial. Participants were 210 newborn
      infants with birth weight less than 1251 grams. The trial was unblinded but
      otherwise of good methodological quality. This trial compared removal of an
      umbilical venous catheter within 10 days after insertion (and replacement with a
      peripheral cannula or a percutaneously inserted central catheter as required)
      versus expectant management (UVC in place up to 28 days). More infants in the
      early planned removal group than in the expectant management group (83 vs 33)
      required percutaneous insertion of a central catheter (PICC). Trial results
      showed no difference in the incidence of catheter-related bloodstream infection
      (RR 0.65, 95% CI 0.35 to 1.22), in hospital mortality (RR 1.12, 95% CI 0.42 to
      2.98), in catheter-associated thrombus necessitating removal (RR 0.33, 95%
      confidence interval 0.01 to 7.94), or in other morbidity. GRADE assessment
      indicated that the quality of evidence was "low" at outcome level principally as
      the result of imprecision and risk of surveillance bias due to lack of blinding
      in the included trial. AUTHORS' CONCLUSIONS: Currently available trial data are
      insufficient to show whether early planned removal of umbilical venous catheters
      reduces risk of infection, mortality, or other morbidity in newborn infants. A
      large, simple, and pragmatic randomised controlled trial is needed to resolve
      this ongoing uncertainty.

PMID- 29017006
TI  - Conformational Smear Characterization and Binning of Single-Molecule Conductance
      Measurements for Enhanced Molecular Recognition.
AB  - Electronic conduction or charge transport through single molecules depends
      primarily on molecular structure and anchoring groups and forms the basis for a
      wide range of studies from molecular electronics to DNA sequencing. Several high
      throughput nanoelectronic methods such as mechanical break junctions, nanopores,
      conductive atomic force microscopy, scanning tunneling break junctions, and
      static nanoscale electrodes are often used for measuring single-molecule
      conductance. In these measurements, "smearing" due to conformational changes and
      other entropic factors leads to large variances in the observed molecular
      conductance, especially in individual measurements. Here, we show a method for
      characterizing smear in single-molecule conductance measurements and demonstrate
      how binning measurements according to smear can significantly enhance the use of
      individual conductance measurements for molecular recognition. Using quantum
      point contact measurements on single nucleotides within DNA macromolecules, we
      demonstrate that the distance over which molecular junctions are maintained is a
      measure of smear, and the resulting variance in unbiased single measurements
      depends on this smear parameter. Our ability to identify individual DNA
      nucleotides at 20* coverage increases from 81.3% accuracy without smear analysis
      to 93.9% with smear characterization and binning (SCRIB). Furthermore, merely 7
      conductance measurements (7* coverage) are needed to achieve 97.8% accuracy for
      DNA nucleotide recognition when only low molecular smear measurements are used,
      which represents a significant improvement over contemporary sequencing methods.
      These results have important implications in a broad range of molecular
      electronics applications from designing robust molecular switches to
      nanoelectronic DNA sequencing.

PMID- 29017007
TI  - DMSO: A Mixed-Competitive Inhibitor of Human Acetylcholinesterase.
AB  - Dimethyl sulfoxide (DMSO) is the most common organic solvent used in biochemical
      and cellular assays during drug discovery programs. Despite its wide use, the
      effect of DMSO on several enzyme classes, which are crucial targets of the new
      therapeutic agents, are still unexplored. Here, we report the detailed
      biochemical analysis of the effects of DMSO on the human acetylcholine-degrading
      enzyme, acetylcholinesterase (AChE), the primary target of current Alzheimer's
      therapeutics. Our analysis showed that DMSO is a considerably potent and highly
      selective irreversible mixed-competitive inhibitor of human AChE with IC50 values
      in the lower millimolar range, corresponding to 0.88% to 2.6% DMSO (v/v). Most
      importantly, 1-4% (v/v) DMSO, the commonly used experimental concentrations,
      showed ~37-80% inhibition of human AChE activity. We believe that our results
      will assist in developing stringent protocols and help in the better
      interpretation of experimental outcomes during screening and biological
      evaluation of new drugs.

PMID- 29017008
TI  - Template-Free Hierarchical Self-Assembly of Iron Diselenide Nanoparticles into
      Mesoscale Hedgehogs.
AB  - The ability of semiconductor nanoparticles (NPs) to self-assemble has been known
      for several decades. However, the limits of the geometrical and functional
      complexity for the self-assembled nanostructures made from simple often
      polydispersed NPs are still continuing to amaze researchers. We report here the
      self-assembly of primary ~2-4 nm FeSe2 NPs with puck-like shapes into either (a)
      monocrystalline nanosheets ~5.5 nm thick and ~1000 nm in lateral dimensions or
      (b) mesoscale hedgehogs ~550 nm in diameter with spikes of ~250 nm in length, and
      ~10-15 nm in diameter, the path of the assembly is determined by the
      concentration of dodecanethiol (DT) in the reaction media. The nanosheets
      represent the constitutive part of hedgehogs. They are rolled into scrolls and
      assembled around a single core with distinct radial orientation forming nanoscale
      "needles" approximately doubling its fractal dimension of these objects. The core
      is assembled from primary NPs and nanoribbons. The size distribution of the
      mesoscale hedgehogs can be as low as 3.8%, indicating a self-limited mechanism of
      the assembly. Molecular dynamics simulation indicates that the primary FeSe2
      particles have mobile edge atoms and asymmetric basal surfaces. The top-bottom
      asymmetry of the puck-like NPs originates from the Fe-rich/Se-rich stripes on the
      (011) surface of the orthorhombic FeSe2 crystal lattice, displaying 2.7 nm
      periodicity that is comparable to the lateral size of the primary NPs. As the
      concentration of DT increases, the NPs bind to additional metal sites, which
      increases the chemical and topographic asymmetry and switches the assembly
      pathways from nanosheets to hedgehogs. These results demonstrate that the self
      assembly of NPs with non-biological surface ligands and without any biological
      templates results in morphogenesis of inorganic superstructures with complexity
      comparable to that of biological assemblies, for instance mimivirus. The
      semiconductor nature of FeSe2 hedgehogs enables their utilizations in catalysis,
      drug delivery, optics, and energy storage.

PMID- 29017009
TI  - Plasma-Facilitated Synthesis of Amidoxime/Carbon Nanofiber Hybrids for Effective
      Enrichment of 238U(VI) and 241Am(III).
AB  - Plasma- and chemical-grafted amidoxime/carbon nanofiber hybrids (p-AO/CNFs and c
      AO/CNFs) were utilized to remove 238U(VI) and 241Am(III) from aqueous solutions,
      seawater, and groundwater. Characteristic results indicated more nitrogen
      containing groups in p-AO/CNFs compared to c-AO/CNFs. The maximum adsorption
      capacities of p-AO/CNFs at pH 3.5 and T = 293 K (588.24 mg of 238U(VI)/g and
      40.79 mg of 241Am(III)/g from aqueous solutions, respectively) were significantly
      higher than those of c-AO/CNFs (263.18 and 22.77 mg/g for 238U(VI) and
      241Am(III), respectively), which indicated that plasma-grafting was a highly
      effective, low-cost, and environmentally friendly method. Adsorption of 238U(VI)
      on AO/CNFs from aqueous solutions was significantly higher than that of 238U(VI)
      from seawater and groundwater; moreover, AO/CNFs displayed the highest effective
      selectivity for 238U(VI) compared to the other radionuclides. Adsorption of
      238U(VI) onto AO/CNFs created inner-sphere complexes (e.g., U-C shells) as shown
      by X-ray absorption fine structure analysis, which was supported by surface
      complexation modeling. Three inner-sphere complexes gave excellent fits to pH
      edge and isothermal adsorption of 238U(VI) on the AO/CNFs. These observations are
      crucial for the utilization of plasma-grafted, AO-based composites in the
      preconcentration and immobilization of lanthanides and actinides in environmental
      remediation.

PMID- 29017010
TI  - On Light-Induced Photoconversion of B800 Bacteriochlorophylls in the LH2 Antenna
      of the Purple Sulfur Bacterium Allochromatium vinosum.
AB  - The B800-850 LH2 antenna from the photosynthetic purple sulfur bacterium
      Allochromatium vinosum exhibits an unusual spectral splitting of the B800
      absorption band; i.e., two bands are well-resolved at 5 K with maxima at 805 nm
      (B800R) and 792 nm (B800B). To provide more insight into the nature of the B800
      bacteriochlorophyll (BChl) a molecules, high-resolution hole-burning (HB)
      spectroscopy is employed. Both white light illumination and selective laser
      excitations into B800R or B800B lead to B800R -> B800B phototransformation.
      Selective excitation into B800B leads to uncorrelated excitation energy transfer
      (EET) to B800R and subsequent B800R -> B800B phototransformation. The B800B ->
      B800R EET time is 0.9 +/- 0.1 ps. Excitation at 808.4 nm (into the low-energy
      side of B800R) shows that the lower limit of B800R -> B850 EET is about 2 ps, as
      the B800R -> B800B phototransformation process could contribute to the
      corresponding zero-phonon hole width. The phototransformation of B800R leads to a
      ~ 200 cm-1 average blue-shift of transition energies, i.e., B800R changes into
      B800B. We argue that it is unlikely that B800-B850 excitonic interactions give
      rise to a splitting of the B800 band. We propose that the latter is caused by
      different protein conformations that can lead to both strong or weak hydrogen
      bond(s) between B800 pigments and the protein scaffolding. Temperature-dependent
      absorption spectra of B800, which revealed a well-defined isosbestic point,
      support a two-site model, likely with strongly and weakly hydrogen-bonded B800
      BChls. Thus, BChls contributing to B800R and B800B could differ in the position
      of the proton in the BChl carbonyl-protein hydrogen bond, i.e., proton dynamics
      along the hydrogen bond may well be the major mechanism of this
      phototransformation. However, the effective tunneling mass is likely larger than
      the proton mass.

PMID- 29017011
TI  - Altered Volatile Organic Compound Profile in Transgenic Rats Bearing A53T
      Mutation of Human alpha-Synuclein: Comparison with Dopaminergic and Serotonergic
      Denervation.
AB  - Early diagnosis of Parkinson's disease (PD) is of great importance due its
      progressive phenotype. Neuroprotective drugs could potentially slow down disease
      progression if used at early stages. Previously, we have reported an altered
      content of volatile organic compounds (VOCs) in the breath of rats following a
      50% reduction in striatal dopamine (DA) content induced by 6-hydroxydopamine. We
      now report on the difference in the breath-print and content of VOCs between rats
      with mild and severe lesions of DA neurons, serotonergic neuronal lesions, and
      transgenic (Tg) rats carrying the PD-producing A53T mutation of the SNCA (alpha
      synuclein) gene. The Tg rats had an increased content of 3-octen-1-ol and 4
      chloro-3-methyl phenol in blood, while in brain tissue, hexanal, hexanol, and 2,3
      octanedione were present in controls but absent in Tg rats. Levels of 1-heptyl-2
      methyl cyclopropane were increased in brain tissue of Tg rats. The data confirm
      the potential of breath analysis for detection of human idiosyncratic as well as
      autosomal dominant PD.

PMID- 29017013
TI  - Persistent Self-Association of Solute Molecules in Solution.
AB  - The structural evolvement of a solute determines the crystallization outcome. The
      self-association mechanism leading to nucleation, however, remains poorly
      understood. Our current study explored the solution chemistry of a model
      compound, tolfenamic acid (TFA), in three different solvents mainly by solution
      NMR. It was found that hydrogen-bonded pairs of solute-solute or solute-solvent
      stack with each through forming a much weaker pi-pi interaction as the
      concentration increases. Depending on the solvent, configurations of the solution
      species may be retained in the resultant crystal structure or undergo
      rearrangement. Yet, the pi-pi stacking is always retained in the crystal
      regardless of the solvent used for the crystallization. The finding suggests that
      nucleation not only involves the primary intermolecular interaction (hydrogen
      bonding) but also engages the secondary forces in the self-assembly process.

PMID- 29017012
TI  - Reactive Transport of U and V from Abandoned Uranium Mine Wastes.
AB  - The reactive transport of uranium (U) and vanadium(V) from abandoned mine wastes
      collected from the Blue Gap/Tachee Claim-28 mine site in Arizona was investigated
      by integrating flow-through column experiments with reactive transport modeling,
      and electron microscopy. The mine wastes were sequentially reacted in flow
      through columns at pH 7.9 (10 mM HCO3-) and pH 3.4 (10 mM CH3COOH) to evaluate
      the effect of environmentally relevant conditions encountered at Blue Gap/Tachee
      on the release of U and V. The reaction rate constants (km) for the dissolution
      of uranyl-vanadate (U-V) minerals predominant at Blue Gap/Tachee were obtained
      from simulations with the reactive transport software, PFLOTRAN. The estimated
      reaction rate constants were within 1 order of magnitude for pH 7.9 (km = 4.8 *
      10-13 mol cm-2 s-1) and pH 3.4 (km = 3.2 * 10-13 mol cm-2 s-1). However, the
      estimated equilibrium constants (Keq) for U-V bearing minerals were more than 6
      orders of magnitude different for reaction at circumneutral pH (Keq = 10-38.65)
      compared to acidic pH (Keq = 10-44.81). These results coupled with electron
      microscopy data suggest that the release of U and V is affected by water pH and
      the crystalline structure of U-V bearing minerals. The findings from this
      investigation have important implications for risk exposure assessment,
      remediation, and resource recovery of U and V in locations where U-V-bearing
      minerals are abundant.

PMID- 29017014
TI  - Effect of Initial Speciation of Copper- and Silver-Based Nanoparticles on Their
      Long-Term Fate and Phytoavailability in Freshwater Wetland Mesocosms.
AB  - Ag0- and CuO-engineered nanomaterials (ENMs) or their sulfidized forms are
      introduced into freshwater wetlands through wastewater effluent and agricultural
      runoff. Knowledge about the rates of transformations of these ENMs in realistic
      environments and the impact of the form of the incoming ENM (i.e., sulfidized or
      pristine) on bioavailability and fate is limited. Here, five freshwater wetland
      mesocosms were exposed to 3 g of total metal as CuO, CuS, Ag0, or Ag2S ENMs or
      soluble CuNO3 added weekly for 1 month. Total metal and metal speciation was
      measured in sediment and plant samples collected 1, 3, 6, and 9 months after
      addition. The form of the added ENM did not affect the metal distribution, and
      ENMs distributed similarly to added ionic Cu or Ag. For the dosing condition
      used, ~50% of the added Ag or Cu metal mass was found in Egeria densa plant
      tissue, with the remainder primarily in the surficial sediment. Ag0 and CuO ENMs
      transformed quickly in sediment, with no evidence of CuO and only ~4% of silver
      present as Ag0 ENM 1 week after the last ENM addition. In contrast to sediment,
      Ag0 and CuO ENMs were persistent in E. densa tissues for up to 9 and 6 months,
      respectively. The persistence of ENMs in E. densa suggests that chronic
      exposures, or food web transfers, for both the transformed and the initially
      added ENMs are possible.

PMID- 29017015
TI  - A Twelve-Week Lifestyle Program to Improve Cardiometabolic, Behavioral, and
      Psychological Health in Hispanic Children and Adolescents.
AB  - OBJECTIVES: To examine the effectiveness of a 12-week lifestyle program on
      cardiometabolic, behavioral, and psychological outcomes among overweight Hispanic
      children and adolescents. DESIGN: A case series study with pre- and post-test
      analyses. Subjects/Settings/Location: A convenience sample of high-risk pediatric
      primary care patients (n = 22; 6 girls, 16 boys; M age = 11.73 +/- 1.39 years)
      and their guardians in the Southeast United States. INTERVENTION: Twice per week
      60 min (total of 24 h) of moderate-to-vigorous intensity boxing exercise
      training, 12 h of nutrition education for guardians, and a 30-min pediatrician
      appointment. OUTCOME MEASURES: Cardiometabolic (height [m], weight [kg], waist
      circumference [cm], body-mass index [BMI], BMI-z, BMI%, cholesterol [mg/dL],
      triglycerides [mg/dL], glucose [mg/dL], and low-density lipoprotein and high
      density lipoprotein cholesterol [mg/dL]), behavioral (objective free time
      physical activity [PA] and sedentary time [min/day]), and psychological (self
      determined exercise motivation) outcomes were measured/calculated, and paired
      samples t-tests were conducted. RESULTS: A significant reduction was observed in
      waist circumference t(17) = -2.57, p = 0.020, d = 0.64; BMI% t(15) = -2.53, p =
      0.023, d = 0.20; fasting glucose t(15) = -6.43, p < 0.001, d = 1.67; and
      amotivation (-) t(17) = -2.29, p = 0.036, d = 0.64; whereas a significant
      increase was identified in moderate t(10) = 4.01, p = 0.002, d = 1.23 and
      vigorous t(10) = 3.41, p = 0.007, d = 1.07 intensity PA; intrinsic motivation
      t(17) = 2.71, p = 0.015, d = 0.38; and introjected regulation t(17) = 2.74, p =
      0.014, d = 0.64. CONCLUSIONS: A 12-week lifestyle program can be effective in
      improving selected health markers among overweight Hispanic children and
      adolescents. The positive changes in fasting glucose, BMI, and waist suggest that
      the participants are currently at lower risk for both type 2 diabetes and
      cardiovascular disease as a result of the Confidence, Ownership, Responsibility,
      and Exercise program.

PMID- 29017016
TI  - Participation in moderate-to-vigorous leisure time physical activity is related
      to decreased visceral adipose tissue in adults with spinal cord injury.
AB  - Increased visceral adiposity places individuals with chronic spinal cord injury
      (SCI) at increased risk of cardiometabolic disease. The purpose of this study was
      to identify if people with chronic SCI who participate in any moderate- to
      vigorous-intensity leisure time physical activity (LTPA) have lower visceral
      adipose tissue (VAT) area compared with those who report none. Participants
      included 136 adult men (n = 100) and women (n = 36) with chronic (mean (+/-SD)
      15.6 +/- 11.3 years post-injury) tetraplegia (n = 66) or paraplegia (n = 70)
      recruited from a tertiary rehabilitation hospital. VAT area was assessed via
      whole-body dual-energy X-ray absorptiometry using a Hologic densitometer and the
      manufacturer's body composition software. Moderate-to-vigorous LTPA was assessed
      using the Leisure Time Physical Activity Questionnaire for People with SCI (LTPAQ
      SCI) or the Physical Activity Recall Assessment for People with SCI (PARA-SCI).
      Summary scores were dichotomized into any or no participation in moderate-to
      vigorous LTPA to best represent the intensity described in current population
      specific physical-activity guidelines. Data were analyzed using univariate and
      multiple regression analyses to identify the determinants of VAT. Overall, the
      model explained 67% of the variance in VAT area and included time post-injury,
      age-at-injury, android/gynoid ratio, waist circumference, and moderate-to
      vigorous LTPA. Participation in any moderate-to-vigorous LTPA was significantly
      (95% confidence interval: -34.71 to -2.61, p = 0.02) associated with VAT after
      controlling for injury-related and body-composition correlates. Moderate-to
      vigorous LTPA appears to be related to lower VAT area, suggesting potential for
      LTPA to reduce cardiometabolic disease risk among individuals with chronic SCI.

PMID- 29017017
TI  - The effect of resistance training set configuration on strength, power, and
      hormonal adaptation in female volleyball players.
AB  - The primary purpose of this investigation was to determine the impact of altering
      the set structure during an 8-week resistance training program on anthropometric,
      hormonal, and strength power characteristics. Thirty female volleyball players
      were recruited for participation and then randomly assigned to 1 of 3 resistance
      training groups: (i) cluster sets (CRT; n = 10), (ii) traditional sets (TRT; n =
      10), or (iii) control (CON; n = 10). All athletes were evaluated for thigh and
      arm circumference, vertical jump, 20-m sprint, 4 * 9-m shuttle-run, 1-repetition
      maximum (1RM) back squat, bench press, military press, and deadlift prior to and
      after an 8-week periodized training intervention. Blood samples were taken before
      and after the 8-week training period to evaluate resting testosterone, cortisol,
      and insulin-like growth factor 1 responses to the training period. After 8 weeks
      of training the CRT group displayed a small but significant improvement in
      vertical jump (CRT: effect size (ES) = 038, 7.1%) performance when compared with
      the TRT group (ES = 0.34, 5.6%). Both the CRT and TRT training interventions
      resulted in very large increases in the 1RM squat (CRT: 8.4% +/- 1.2%; TRT: 7.3%
      +/- 0.6%), bench press (CRT: 8.3% +/- 2.0%; TRT: 8.7% +/- 1.9%), military press
      (CRT: 5.7% +/- 1.2%; TRT: 5.5% +/- 1.6%), and deadlift (CRT: 8.2% +/- 1.6%; TRT:
      8.3% +/- 2.2%). There were no significant differences in 20-m sprint or 4 * 9-m
      shuttle run times between the CRT, TRT, and CON groups. These results suggest
      that cluster sets allow for greater improvements in vertical jump performance and
      equal improvements in strength gains to those seen with traditional sets.

PMID- 29017020
TI  - MS Research Australia Progress in MS Research 2017.

PMID- 29017018
TI  - What is the impact of population ageing on the future provision of end-of-life
      care? Population-based projections of place of death.
AB  - BACKGROUND: Population ageing represents a global challenge for future end-of
      life care. Given new trends in place of death, it is vital to examine where the
      rising number of deaths will occur in future years and implications for health
      and social care. AIM: To project where people will die from 2015 to 2040 across
      all care settings in England and Wales. DESIGN: Population-based trend analysis
      and projections using simple linear modelling. Age- and gender-specific
      proportions of deaths in hospital, care home, home, hospice and 'other' were
      applied to numbers of expected future deaths. Setting/population: All deaths
      (2004-2014) from death registration data and predicted deaths (2015-2040) from
      official population forecasts in England and Wales. RESULTS: Annual deaths are
      projected to increase from 501,424 in 2014 (38.8% aged 85 years and over) to
      635,814 in 2040 (53.6% aged 85 years and over). Between 2004 and 2014,
      proportions of home and care home deaths increased (18.3%-22.9% and 16.7%- 21.2%)
      while hospital deaths declined (57.9%-48.1%). If current trends continue, numbers
      of deaths in care homes and homes will increase by 108.1% and 88.6%, with care
      home the most common place of death by 2040. If care home capacity does not
      expand and additional deaths occur in hospital, hospital deaths will start rising
      by 2023. CONCLUSION: To sustain current trends, end-of-life care provision in
      care homes and the community needs to double by 2040. An infrastructure across
      care settings that supports rising annual deaths is urgently needed; otherwise,
      hospital deaths will increase.

PMID- 29017019
TI  - Results of Combined, Single-Session Arthrocentesis and Dextrose Prolotherapy for
      Symptomatic Temporomandibular Joint Syndrome: A Case Series.
AB  - OBJECTIVE: Arthrocentesis and prolotherapy are nonsurgical treatments for
      temporomandibular joint (TMJ) diseases. This study aimed to evaluate the
      treatment of hypermobility, pain, and displacement of the TMJ by consecutively
      performing arthrocentesis and prolotherapy in the same session. MATERIALS AND
      METHODS: In this study, 10 adults with disc displacement and painful, hypermobile
      TMJ were selected. Arthrocentesis and prolotherapy were consecutively performed
      using a 30% dextrose solution that was simultaneously injected into five areas:
      posterior disc attachment, superior joint space, superior and inferior capsular
      attachments, and stylomandibular ligament. Paired t-test, McNemar test, and chi
      square test were used to assess the maximum mouth opening, clicking sounds, pain,
      and subluxation of the TMJ. Patients with rheumatoid arthritis and parafunctional
      habits such as teeth clenching and grinding and biting of the cheeks or any other
      objects and those who had undergone surgery were excluded from this study.
      RESULTS: A total of 10 participants (36.20 +/- 7.06 years old, 7 women and 3 men)
      received a single treatment session of combined arthrocentesis and prolotherapy
      at the same office visit. Subluxation frequency and pain significantly decreased
      after the first week of treatment (p < 0.05). Subluxation also decreased at the 3
      month follow-up (p < 0.05). Clicking sound values did not significantly change at
      any of the follow-up time points. Maximum mouth opening values decreased at all
      follow-up time points compared to baseline (p < 0.05). CONCLUSION: A single
      session of combined arthrocentesis and prolotherapy to treat symptomatic TMJ
      safely and significantly improved the subluxation and pain after 1 week and
      subluxation after 3 months compared to baseline status. The maximum mouth opening
      significantly decreased at all follow-up time points. Future studies assessing
      multiple treatment sessions are warranted.

PMID- 29017021
TI  - Chemical composition of the essential oils isolated from peel of three citrus
      species and their mosquitocidal activity against Culex pipiens.
AB  - Three essential oils (EOs) were isolated from the peel of citrus fruits Citrus
      reticulata L., Citrus reticulata chinase Blanco and Citrus sinensis (L.) Osbeck
      (Family: Rutaceae) and evaluated against Culex pipiens L.1758 (Family:
      Culicidae). Chemical composition indicated that the EOs were rich in essential
      phytochemicals including hydrocarbons, monoterpenes and sesquiterpenes. These
      constituents revealed some variability among the oils displaying interesting
      chemotypes limonene (35-51%), 1R-alpha-pinene (1.04-2.5%), gamma-terpinene (0.46
      5.65%) and sabinene (0.51-5.42%). The toxicity proved that C. sinensis oil had
      more effect than C. reticulata chinase and C. reticulata oils against larvae
      (LC50 = 15.35, 16.11 and 32.84 mg/L, respectively). However, C. reticulate was
      the most active as fumigant against adults (LC50 2.74 MUL/L air). The in vivo
      effect on acetylcholine esterase (AChE), carboxyl esterase (CbE), acid
      phosphatase (ACP), alkaline phosphatase (ALP), adenosine triphosphatase (ATPase)
      and glutathione-S-transferase (GST) were also demonstrated. To the best of our
      knowledge, this is the first report about the chemical composition and
      mosquitocidal activity of C. reticulata chinase essential oils. Conclusively, the
      tested essential oils could be used as eco-friendly alternatives in mosquitoes
      control programme.

PMID- 29017022
TI  - Isometric parameters in the monitoring of maximal strength, power, and
      hypertrophic resistance-training.
AB  - This study monitored strength-training adaptations via isometric parameters
      throughout 2 * 10 weeks of hypertrophic (HYP I-II) or 10 weeks maximum strength
      (MS) followed by 10 weeks power (P) training with untrained controls. Trainees
      performed bilateral isometric leg press tests analyzed for peak force (maximal
      voluntary contraction (MVC)) and rate of force development (RFD) every 3.5 weeks.
      These parameters were compared with dynamic performance, voluntary and
      electrically induced isometric contractions, muscle activity, and cross-sectional
      area (CSA) in the laboratory before and after 10 and 20 weeks. RFD increased
      similarly during the first 7 weeks (HYP I, 44% +/- 53%; MS, 48% +/- 55%, P <
      0.05), but RFD continued to increase up to 65% +/- 61% from baseline (P < 0.01)
      only during P. These increases were concomitant with enhanced dynamic
      performances of 1-repetition maximum (1RM) (HYP I, 8% +/- 6%; MS, 11% +/- 6%, P <
      0.001), and explosive repetitions during P (11% +/- 15%, P < 0.05). Time to reach
      peak RFD differed (P < 0.001) between HYP (mean 42 +/- 20 ms) and MS-P (mean 31
      +/- 12 ms) groups because of training. The changes in MVC correlated with the
      changes in CSA during weeks 1-20 (HYP I-II, r = 0.664; MS-P, r = 0.595, P <=
      0.05), as well as changes in 1RM (r = 0.724, P < 0.05) during weeks 11-20 (HYP
      II). Muscle activity increased during MS and P only. Both MVC and RFD
      improvements reflected combinations of central and peripheral adaptations. RFD
      parameters may be effective tools to evaluate adaptations, particularly during
      maximal strength/power training, while MVC cannot distinguish between strength or
      muscle mass changes. Monitoring RFD provided important information regarding
      plateaus in RFD improvement, which were observed in dynamic explosive
      performances after HYP II compared with P.

PMID- 29017024
TI  - Genetic heterogeneity among Vibrio alginolyticus strains, and design of a PCR
      based identification method using gyrB gene sequence.
AB  - Vibrio alginolyticus, a pathogen among humans and marine animals, is ubiquitous
      in marine environments. The aims of this study were to analyze the relationships
      between genetic diversity and origins, and to develop new primers based on the
      gyrB sequence to identify V. alginolyticus isolated from various sources. To
      determine the genetic diversity of this bacterium, an arbitrarily primed
      polymerase chain reaction (AP-PCR) technique was performed on 36 strains of V.
      alginolyticus isolated from diarrhea patients and from diseased marine animals
      and environments in southern Thailand. The results showed distinct DNA
      fingerprints of all strains, indicating that they are genetically heterogeneous.
      For species-specific identification of V. alginolyticus, primers targeting the
      gyrB gene of V. alginolyticus were developed. Thirty reference Vibrio spp., 13
      non-Vibrio spp., and 160 strains of V. alginolyticus isolated from various
      sources in southern Thailand were used to evaluate the specificity of these
      primers. Our results showed that the gyrB primers could specifically identify V.
      alginolyticus from all sample types. In addition, the detection limit of the PCR
      was at least 95 pg of DNA template. Therefore, we concluded that the newly
      designed gyrB primers are rapid, highly sensitive, and specific to identify V.
      alginolyticus isolated from various sources.

PMID- 29017026
TI  - Germline Genome Protection on an Evolutionary Treadmill.
AB  - Preservation of genome integrity is a conserved, essential function, yet genome
      defense machinery evolves rapidly. In this issue of Developmental Cell, Parhad et
      al. (2017) harness an evolution-guided approach to define the genetic
      determinants of genome defense and to reveal the molecular and cellular
      mechanisms shaped by adaptive evolution.

PMID- 29017025
TI  - Global nursing in an Ebola viral haemorrhagic fever outbreak: before, during and
      after deployment.
AB  - BACKGROUND: Nurses are on the forefront and play a key role in global disaster
      responses. Nevertheless, they are often not prepared for the challenges they are
      facing and research is scarce regarding the nursing skills required for first
      responders during a disaster situation. OBJECTIVES: To investigate how returnee
      nursing staff experienced deployment before, during and after having worked for
      the Red Cross at an Ebola Treatment Center in Kenema, West Africa, and to supply
      knowledge on how to better prepare and support staff for viral haemorrhagic fever
      outbreaks. METHODS: A descriptive, cross-sectional approach. Questionnaires were
      administered to nurses having worked with patients suffering from Ebola in 2014
      and 2015. Data collection covered aspects of pre-, during and post-deployment on
      clinical training, personal health, stress management, leadership styles, socio
      cultural exposure and knowledge transfer, as well as attitudes from others. Data
      was analysed using both quantitative and qualitative methods. RESULTS: Response
      rate was 88%: forty-four nurses from 15 different countries outside West Africa
      answered the questionnaire. The respondents identified the following needs for
      improvement: increased mental health and psychosocial support and hands-on coping
      strategies with focus on pre- and post-deployment; more pre-deployment task
      oriented clinical training; and workload reduction, as exhaustion is a risk for
      safety. CONCLUSIONS: This study supplies knowledge on how to better prepare
      health care staff for future viral haemorrhagic fever outbreaks and other
      disasters. Participants were satisfied with their pre-deployment physical health
      preparation, whereas they stressed the importance of mental health support
      combined with psychosocial support after deployment. Furthermore, additional pre
      clinical training was requested.

PMID- 29017023
TI  - Maternal iron nutriture as a critical modulator of fetal alcohol spectrum
      disorder risk in alcohol-exposed pregnancies.
AB  - Alcohol consumption during pregnancy places the fetus at risk for permanent
      physical, cognitive, and behavioral impairments, collectively termed fetal
      alcohol spectrum disorder (FASD). However, prenatal alcohol exposure (PAE)
      outcomes vary widely, and growing evidence suggests that maternal nutrition is a
      modifying factor. Certain nutrients, such as iron, may modulate FASD outcomes.
      Untreated gestational iron deficiency (ID) causes persistent neurodevelopmental
      deficits in the offspring that affect many of the same domains damaged by PAE.
      Although chronic alcohol consumption enhances iron uptake and elevates liver iron
      stores in adult alcoholics, alcohol-abusing premenopausal women often have low
      iron reserves due to menstruation, childbirth, and poor diet. Recent
      investigations show that low iron reserves during pregnancy are strongly
      associated with a worsening of several hallmark features in FASD including
      reduced growth and impaired associative learning. This review discusses recent
      clinical and animal model findings that maternal ID worsens fetal outcomes in
      response to PAE. It also discusses underlying mechanisms by which PAE disrupts
      maternal and fetal iron homeostasis. We suggest that alcohol-exposed ID
      pregnancies contribute to the severe end of the FASD spectrum.

PMID- 29017028
TI  - Lessons from Yeast on How to Avoid Stress Eating.
AB  - Cellular survival during periods of acute environmental stress is essential for
      single-celled organisms. Reporting in Nature Cell Biology, Saad et al. (2017)
      identify reversible aggregation of the metabolic enzyme pyruvate kinase under
      environmental stress and propose a method to protect and store proteins for
      immediate use post-stress.

PMID- 29017027
TI  - Microtubule Sliding within the Bridging Fiber Pushes Kinetochore Fibers Apart to
      Segregate Chromosomes.
AB  - During cell division, mitotic spindle microtubules segregate chromosomes by
      exerting forces on kinetochores. What forces drive chromosome segregation in
      anaphase remains a central question. The current model for anaphase in human
      cells includes shortening of kinetochore fibers and separation of spindle poles.
      Both processes require kinetochores to be linked with the poles. Here we show, by
      combining laser ablation, photoactivation, and theoretical modeling, that
      kinetochores can separate without any attachment to one spindle pole. This
      separation requires the bridging fiber, a microtubule bundle that connects sister
      kinetochore fibers. Bridging fiber microtubules in intact spindles slide apart
      with kinetochore fibers, indicating strong crosslinks between them. We conclude
      that sliding of microtubules within the bridging fibers drives pole separation
      and pushes kinetochore fibers poleward by the friction of passive crosslinks
      between these fibers. Thus, sliding within the bridging fiber works together with
      the shortening of kinetochore fibers to segregate chromosomes.

PMID- 29017030
TI  - Accessing the Phenotype Gap: Enabling Systematic Investigation of Paralog
      Functional Complexity with CRISPR.
AB  - Single-gene knockout experiments can fail to reveal function in the context of
      redundancy, which is frequently observed among duplicated genes (paralogs) with
      overlapping functions. We discuss the complexity associated with studying
      paralogs and outline how recent advances in CRISPR will help address the
      "phenotype gap" and impact biomedical research.

PMID- 29017029
TI  - Fgf10-Hippo Epithelial-Mesenchymal Crosstalk Maintains and Recruits Lung Basal
      Stem Cells.
AB  - The lung harbors its basal stem/progenitor cells (BSCs) in the protected
      environment of the cartilaginous airways. After major lung injuries, BSCs are
      activated and recruited to sites of injury. Here, we show that during
      homeostasis, BSCs in cartilaginous airways maintain their stem cell state by
      downregulating the Hippo pathway (resulting in increased nuclear Yap), which
      generates a localized Fgf10-expressing stromal niche; in contrast, differentiated
      epithelial cells in non-cartilaginous airways maintain quiescence by activating
      the Hippo pathway and inhibiting Fgf10 expression in airway smooth muscle cells
      (ASMCs). However, upon injury, surviving differentiated epithelial cells spread
      to maintain barrier function and recruit integrin-linked kinase to adhesion
      sites, which leads to Merlin degradation, downregulation of the Hippo pathway,
      nuclear Yap translocation, and expression and secretion of Wnt7b. Epithelial
      derived Wnt7b, then in turn, induces Fgf10 expression in ASMCs, which extends the
      BSC niche to promote regeneration.

PMID- 29017031
TI  - Angiopoietin-like 4 Is a Wnt Signaling Antagonist that Promotes LRP6 Turnover.
AB  - Angiopoietin-like 4 (ANGPTL4) is a secreted signaling protein that is implicated
      in cardiovascular disease, metabolic disorder, and cancer. Outside of its role in
      lipid metabolism, ANGPTL4 signaling remains poorly understood. Here, we identify
      ANGPTL4 as a Wnt signaling antagonist that binds to syndecans and forms a ternary
      complex with the Wnt co-receptor Lipoprotein receptor-related protein 6 (LRP6).
      This protein complex is internalized via clathrin-mediated endocytosis and
      degraded in lysosomes, leading to attenuation of Wnt/beta-catenin signaling.
      Angptl4 is expressed in the Spemann organizer of Xenopus embryos and acts as a
      Wnt antagonist to promote notochord formation and prevent muscle differentiation.
      This unexpected function of ANGPTL4 invites re-interpretation of its diverse
      physiological effects in light of Wnt signaling and may open therapeutic avenues
      for human disease.

PMID- 29017033
TI  - Russia's new Lysenkoism.
AB  - During the late 1940s and 1950s, a pseudo-scientific concept based on Marxist
      Leninist ideology became internationally known as 'Lysenkoism'. Lysenkoism was a
      neo-Lamarckian idea, claiming that in crop plants, such as wheat, environmental
      influences are heritable via all cells of the organism. Lysenkoism was applied to
      agriculture during the Stalin era with disastrous consequences. Despite the
      triumphs of modern genetics, and the disproval of Lysenkoism, recent years have
      seen a 're-thinking' of this doctrine in Russia. This disturbing pro-Lysenko
      movement, which is accompanied by a growing sympathy for Stalin, claims to have
      its scientific roots in modern epigenetics, specifically the heritability of
      variation by mechanisms other than changes in DNA sequence. Based on recent
      research on the model plant Arabidopsis thaliana, its is clear that Lysenkoism
      has nothing to do with heritable 'epigenetic' modifications. Biologists should
      defend science against ideological and political interferences.

PMID- 29017034
TI  - Transvection.
AB  - Fukaya and Levine explain the basic features of the genetic phenomenon of
      transvection, a special class of genetic complementation of mutant alleles on
      homologous chromosomes.

PMID- 29017035
TI  - Bee cognition.
AB  - Maeterlinck did not mean to suggest that honeybees rival humans in intelligence -
      rather he saw in the bee a qualitatively different form of intelligence, tailored
      to the challenges of a profoundly different kind of society and lifestyle.
      Insects are strange "aliens from inner space", with sensory and cognitive worlds
      wholly different from our own. The 19th century discovery that ants can detect
      ultraviolet light triggered a golden age in the exploration of the diversity of
      sensory systems of insects (and indeed other animals), identifying such abilities
      as magnetic compasses, electrosensitivity, polarization vision, and peculiar
      locations for sense organs such as the infrared sensors on the abdomens of some
      beetles or photoreceptors on the genitalia of some butterflies. Could insect
      minds be equally strange and diverse?

PMID- 29017032
TI  - A Mechanism Coupling Systemic Energy Sensing to Adipokine Secretion.
AB  - Adipocytes sense systemic nutrient status and systemically communicate this
      information by releasing adipokines. The mechanisms that couple nutritional state
      to adipokine release are unknown. Here, we investigated how Unpaired 2 (Upd2), a
      structural and functional ortholog of the primary human adipokine leptin, is
      released from Drosophila fat cells. We find that Golgi reassembly stacking
      protein (GRASP), an unconventional secretion pathway component, is required for
      Upd2 secretion. In nutrient-rich fat cells, GRASP clusters in close proximity to
      the apical side of lipid droplets (LDs). During nutrient deprivation, glucagon
      mediated increase in calcium (Ca2+) levels, via calmodulin kinase II (CaMKII)
      phosphorylation, inhibits proximal GRASP localization to LDs. Using a
      heterologous cell system, we show that human leptin secretion is also regulated
      by Ca2+ and CaMKII. In summary, we describe a mechanism by which increased
      cytosolic Ca2+ negatively regulates adipokine secretion and have uncovered an
      evolutionarily conserved molecular link between intracellular Ca2+ levels and
      energy homeostasis.

PMID- 29017036
TI  - A combined 3D-SIM/SMLM approach allows centriole proteins to be localized with a
      precision of ~4-5 nm.
AB  - Centrioles are small barrel-shaped structures that form centrosomes and cilia
      [1]. Centrioles assemble around a central cartwheel comprising the Sas-6 and
      Ana2/STIL proteins. The amino termini of nine Sas-6 dimers form a central hub of
      ~12 nm radius from which nine dimer spokes radiate, placing the Sas-6 carboxyl
      termini at the outer edge of the ~60 nm radius cartwheel [2]. Several centriole
      proteins are distributed in a toroid around the cartwheel, and super-resolution
      light microscopy studies have measured the average radii of these ~100-200 nm
      radius toroids with a 'precision' - or standard deviation (s.d. or 1sigma) - of
      +/-~10-40 nm. The organization of Ana2/STIL within the cartwheel, however, has
      not been resolvable. Here, we develop methods to calculate the average toroidal
      radius of centriolar proteins in the ~20-60 nm range with a s.d. of just +/-~4-5
      nm, revealing that the amino and carboxyl termini of Ana2 are located in the
      outer cartwheel region.

PMID- 29017037
TI  - Dawn illumination prepares desert cyanobacteria for dehydration.
AB  - Desert biological soil crusts (BSC), among the harshest environments on Earth,
      are formed by the adhesion of soil particles to polysaccharides excreted mainly
      by filamentous cyanobacteria (see [1] and references therein). These species are
      the main primary producers in this habitat where they cope with various stressors
      including frequent hydration-dehydration cycles. Water is mainly provided as
      early-morning dew, followed by dehydration with rising temperatures and declining
      relative humidity. Earlier studies focused on community structure and
      cyanobacterial activities in various BSCs [1,2]. They identified genes present in
      dehydration-tolerant, but not -sensitive cyanobacteria [3], and suggested that
      abiotic conditions during natural dehydration (Figure 1A) are critical for the
      recovery upon rewetting. Inability of Leptolyngbya ohadii, which is abundant in
      the BSC examined here, to recover after rapid desiccation (Figure 1B) [4]
      suggested that the cells must prepare themselves toward forthcoming dehydration,
      but the nature of the signal involved was unknown. We show here that the rising
      dawn illumination, perceived by photo-sensors, serves as the signal inciting BSC
      inhabiting cyanobacteria to prepare for forthcoming dehydration. L. ohadii
      filaments were exposed to simulated natural conditions from the morning of
      October 14th 2009, using our environmental chamber that enables accurate
      reproduction of BSC environment [4] (Supplemental Figure S1A). Samples were
      withdrawn at specific time points (Figure 1A), followed by RNA extraction and
      global transcript profiling (accession PRJNA391854). Four hours of dehydration
      led to up-regulation of 567 genes and down-regulation of 1597 (by more than 2
      fold). Since BSC-inhabiting organisms have not been used as genetic models, the
      functions of 3258 (43.5% of the 7487 L. ohadii genes [3]) are unknown.
      Nevertheless, a pronounced rise in transcript levels of genes involved in carbon
      metabolism, transport, osmolyte production, energy dissipation and other cellular
      activities was observed. On the other hand, a declining transcript abundance for
      genes involved in light harvesting, photosynthetic metabolism, protein
      biosynthesis, cell division and other pathways was detected. The analysis
      unraveled clear distinctions between early- and late-responding genes.
      Supplemental Table S1 lists the 40 strongest differentially expressed genes
      verified by RT-qPCR and used in further analyses.

PMID- 29017038
TI  - Northern pygmy right whales highlight Quaternary marine mammal interchange.
AB  - The pygmy right whale, Caperea marginata, is the most enigmatic living whale.
      Little is known about its ecology and behaviour, but unusual specialisations of
      visual pigments [1], mitochondrial tRNAs [2], and postcranial anatomy [3] suggest
      a lifestyle different from that of other extant whales. Geographically, Caperea
      represents the only major baleen whale lineage entirely restricted to the
      Southern Ocean. Caperea-like fossils, the oldest of which date to the Late
      Miocene, are exceedingly rare and likewise limited to the Southern Hemisphere
      [4], despite a more substantial history of fossil sampling north of the equator.
      Two new Pleistocene fossils now provide unexpected evidence of a brief and
      relatively recent period in geological history when Caperea occurred in the
      Northern Hemisphere (Figure 1A,B).

PMID- 29017039
TI  - Sleep Origins: Restful Jellyfish Are Sleeping Jellyfish.
AB  - What is the 'simplest' animal that sleeps? When did sleep first evolve? Do all
      animals sleep? Tantalizing hints to answers come from new research showing that
      jellyfish, one of the earliest evolving groups of animals, have a sleep-like
      restful state.

PMID- 29017040
TI  - Plant Biology: Unravelling the Transient Physiological Role for PHO1 in the Seed.
AB  - During seed development, an important transfer of nutrients occurs between the
      seed coat and the embryo. A new study reveals that, for inorganic phosphate (Pi),
      this function is transiently performed by PHO1, a protein associated previously
      with Pi loading into the xylem.

PMID- 29017041
TI  - Evolution: A Parthenogenetic Nematode Shows How Animals Become Sexless.
AB  - Most animals have male and female sexes, implying that sex is ancient and
      beneficial; yet some have survived for millions of years without sex. The genome
      of the parthenogenetic nematode Diploscapter pachys gives clues as to how
      'ancient asexual' animals can exist.

PMID- 29017042
TI  - Retrotransposons: Stowaways in the Primordial Germline.
AB  - In order to succeed, retrotransposon transcripts must identify the subset of
      nuclei that will be transmitted to offspring. A new study reveals that the
      primordial germline is a hideout for retrotransposon transcripts, providing early
      access to future gametes.

PMID- 29017043
TI  - Plant Biology: Rethinking Structure-Function Relationships in Guard Cells.
AB  - Recent findings highlight the role of polar reinforcement in guard cell function,
      which simultaneously improves our understanding of stomatal mechanics and
      questions our long-standing beliefs about structurally important factors.

PMID- 29017044
TI  - Muscle Development: Nucleating Microtubules at the Nuclear Envelope.
AB  - Microtubule-organizing centers move from centrosomes to the nuclear envelope
      during muscle development. The KASH protein Nesprin-1alpha recruits
      pericentriolar material to the surface of myotube nuclei, where it nucleates
      microtubules to ensure even spacing of nuclei within the developing myotube.

PMID- 29017045
TI  - Behavioural Ecology: Spiders Play the Imitation Game.
AB  - Examples of mimicry are widely celebrated because of the remarkable physical
      similarities they entail. A new study shows how an ant-mimicking spider uses
      behaviour to create the illusion of antennae, while walking in a manner
      resembling ants following pheromone trails.

PMID- 29017046
TI  - Insect Vision: A Neuron that Anticipates an Object's Path.
AB  - Dragonflies are superb aerial predators, plucking tiny insect prey from the sky.
      This ability depends on a visual system that has fascinated scientists for
      decades, and now one of its visual-target-detecting neurons has been shown to
      anticipate the image path of prey.

PMID- 29017047
TI  - Cell Biology: Capturing Formin's Mechano-Inhibition.
AB  - Formins polymerize actin filaments for the cytokinetic contractile ring. Using in
      vitro reconstitution of fission yeast contractile ring precursor nodes containing
      formins and myosin, a new study shows that formin-mediated polymerization is
      strongly inhibited upon the capture and pulling of actin filaments by myosin, a
      result that has broad implications for cellular mechanosensing.

PMID- 29017049
TI  - Exploiting the Hidden Treasure of Detained Introns.
AB  - Many mammalian genes contain poorly spliced introns, resulting in nuclear
      detention of partially spliced transcripts, which may be exploited to modulate
      gene expression. In this issue of Cancer Cell, Braun et al. report that the
      arginine methyltransferase PRMT5 is critical for tumor cell proliferation by
      regulating numerous detained introns.

PMID- 29017050
TI  - Neuroblastoma Metastases: Leveraging the Avian Neural Crest.
AB  - Neuroblastoma, an embryonal cancer of neural crest origin, shows metastases
      frequently at diagnosis. In this issue of Cancer Cell, Delloye-Bourgeois and
      colleagues demonstrate that neuroblastoma cell lines and patient-derived
      xenografts engraft and adopt a metastatic program in chick embryos. They identify
      Sema3C as a candidate switch that regulates metastatic spread.

PMID- 29017051
TI  - Tumor Suppression by p53: Bring in the Hippo!
AB  - In this issue of Cancer Cell, Mello et al. investigated how p53 suppresses
      pancreatic cancer and discovered a key role for the tyrosine phosphatase PTPN14,
      a p53 transcriptional target. PTPN14 restrains YAP, curbing its potential
      oncogenic effects. The p53-PTPN14-YAP axis highlights the importance of signaling
      pathway coordination in cancer prevention.

PMID- 29017048
TI  - Embracing Uncertainty in Reconstructing Early Animal Evolution.
AB  - The origin of animals, one of the major transitions in evolution, remains
      mysterious. Many key aspects of animal evolution can be reconstructed by
      comparing living species within a robust phylogenetic framework. However,
      uncertainty remains regarding the evolutionary relationships between two ancient
      animal lineages - sponges and ctenophores - and the remaining animal phyla.
      Comparative morphology and some phylogenomic analyses support the view that
      sponges represent the sister lineage to the rest of the animals, while other
      phylogenomic analyses support ctenophores, a phylum of carnivorous, gelatinous
      marine organisms, as the sister lineage. Here, we explore why different studies
      yield different answers and discuss the implications of the two alternative
      hypotheses for understanding the origin of animals. Reconstruction of ancient
      evolutionary radiations is devilishly difficult and will likely require broader
      sampling of sponge and ctenophore genomes, improved analytical strategies and
      critical analyses of the phylogenetic distribution and molecular mechanisms
      underlying apparently conserved traits. Rather than staking out positions in
      favor of the ctenophores-sister or the sponges-sister hypothesis, we submit that
      research programs aimed at understanding the biology of the first animals should
      instead embrace the uncertainty surrounding early animal evolution in their
      experimental designs.

PMID- 29017052
TI  - Cellular Origin of Androgen Receptor Pathway-Independent Prostate Cancer and
      Implications for Therapy.
AB  - In this issue of Cancer Cell, Bluemn et al. report that ~20% of metastatic
      castration-resistant prostate cancers express neither AR nor neuroendocrine genes
      and show AR pathway-independent growth, driven instead by a FGFR/MAPK/ID1
      signaling cascade. These results provide a strong rationale for co-targeting AR
      bypass pathways with initial AR antagonism.

PMID- 29017053
TI  - Apoptosis, Up the Ante.
AB  - The clinical success of the BH3-mimetic venetoclax has generated increasing
      interest to target BCL2 family proteins in oncology. In this issue of Cancer
      Cell, Reyna and colleagues demonstrate the potential of a pharmacological
      activator of the pro-apoptotic protein BAX to suppress acute myeloid leukemia
      both alone and together with venetoclax.

PMID- 29017055
TI  - Microenvironment-Driven Shift of Cohesion/Detachment Balance within Tumors
      Induces a Switch toward Metastasis in Neuroblastoma.
AB  - Neuroblastoma (NB) is a childhood cancer arising from sympatho-adrenal neural
      crest cells. Disseminated forms have high frequency of multiple tumoral foci
      whose etiology remains unknown; NB embryonic origin limits investigations in
      patients and current models. We developed an avian embryonic model driving human
      NB tumorigenesis in tissues homologous to patients. We found that aggressive NBs
      display a metastatic mode, secondary dissemination via peripheral nerves and
      aorta. Through tumor transcriptional profiling, we found that NB dissemination is
      induced by the shutdown of a pro-cohesion autocrine signal, SEMA3C, which
      constrains the tumoral mass. Lowering SEMA3C levels shifts the balance toward
      detachment, triggering NB cells to collectively evade the tumor. Together with
      patient cohort analysis, this identifies a microenvironment-driven pro-metastatic
      switch for NB.

PMID- 29017054
TI  - The Stromal Niche for Epithelial Stem Cells: A Template for Regeneration and a
      Brake on Malignancy.
AB  - Stromal restraint of cancer growth and progression-emerging as a widespread
      phenomenon in epithelial cancers such as bladder, pancreas, colon, and prostate
      appears rooted in stromal cell niche activity. During normal tissue repair,
      stromal niche signals, often Hedgehog-induced, promote epithelial stem cell
      differentiation as well as self-renewal, thus specifying a regenerating
      epithelial pattern. In the case of cancerous tissue, stromal cell-derived
      differentiation signals in particular may provide a brake on malignant growth.
      Understanding and therapeutic harnessing of the role of stroma in cancer
      restraint may hinge on our knowledge of the signaling programs elaborated by the
      stromal niche.

PMID- 29017056
TI  - Mitotic Spindle Assembly and Genomic Stability in Breast Cancer Require PI3K
      C2alpha Scaffolding Function.
AB  - Proper organization of the mitotic spindle is key to genetic stability, but
      molecular components of inter-microtubule bridges that crosslink kinetochore
      fibers (K-fibers) are still largely unknown. Here we identify a kinase
      independent function of class II phosphoinositide 3-OH kinase alpha (PI3K
      C2alpha) acting as limiting scaffold protein organizing clathrin and TACC3
      complex crosslinking K-fibers. Downregulation of PI3K-C2alpha causes spindle
      alterations, delayed anaphase onset, and aneuploidy, indicating that PI3K-C2alpha
      expression is required for genomic stability. Reduced abundance of PI3K-C2alpha
      in breast cancer models initially impairs tumor growth but later leads to the
      convergent evolution of fast-growing clones with mitotic checkpoint defects. As a
      consequence of altered spindle, loss of PI3K-C2alpha increases sensitivity to
      taxane-based therapy in pre-clinical models and in neoadjuvant settings.

PMID- 29017057
TI  - A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-Ptpn14-Yap Axis in
      Pancreatic Cancer.
AB  - The p53 transcription factor is a critical barrier to pancreatic cancer
      progression. To unravel mechanisms of p53-mediated tumor suppression, which have
      remained elusive, we analyzed pancreatic cancer development in mice expressing
      p53 transcriptional activation domain (TAD) mutants. Surprisingly, the p5353,54
      TAD2 mutant behaves as a "super-tumor suppressor," with an enhanced capacity to
      both suppress pancreatic cancer and transactivate select p53 target genes,
      including Ptpn14. Ptpn14 encodes a negative regulator of the Yap oncoprotein and
      is necessary and sufficient for pancreatic cancer suppression, like p53. We show
      that p53 deficiency promotes Yap signaling and that PTPN14 and TP53 mutations are
      mutually exclusive in human cancers. These studies uncover a p53-Ptpn14-Yap
      pathway that is integral to p53-mediated tumor suppression.

PMID- 29017060
TI  - Integrating Proteomics and Transcriptomics for Systematic Combinatorial Chimeric
      Antigen Receptor Therapy of AML.
AB  - Chimeric antigen receptor (CAR) therapy targeting CD19 has yielded remarkable
      outcomes in patients with acute lymphoblastic leukemia. To identify potential CAR
      targets in acute myeloid leukemia (AML), we probed the AML surfaceome for
      overexpressed molecules with tolerable systemic expression. We integrated large
      transcriptomics and proteomics datasets from malignant and normal tissues, and
      developed an algorithm to identify potential targets expressed in leukemia stem
      cells, but not in normal CD34+CD38- hematopoietic cells, T cells, or vital
      tissues. As these investigations did not uncover candidate targets with a profile
      as favorable as CD19, we developed a generalizable combinatorial targeting
      strategy fulfilling stringent efficacy and safety criteria. Our findings indicate
      that several target pairings hold great promise for CAR therapy of AML.

PMID- 29017061
TI  - Decreased functional connectivity in schizophrenia: The relationship between
      social functioning, social cognition and graph theoretical network measures.
AB  - Schizophrenia is a complex disorder in which abnormalities in brain connectivity
      and social functioning play a central role. The aim of this study is to explore
      small-world network properties, and understand their relationship with social
      functioning and social cognition in the context of schizophrenia, by testing
      functional connectivity differences in network properties and its relation to
      clinical behavioral measures. Resting-state fMRI time series data were acquired
      from 23 patients diagnosed with schizophrenia and 23 healthy volunteers. The
      results revealed that patients with schizophrenia show significantly decreased
      connectivity between a range of brain regions, particularly involving connections
      among the right orbitofrontal cortex, bilateral putamen and left amygdala.
      Furthermore, topological properties of functional brain networks in patients with
      schizophrenia were characterized by reduced path length compared to healthy
      controls; however, no significant difference was found for clustering
      coefficient, local efficiency or global efficiency. Additionally, we found that
      nodal efficiency of the amygdala and the putamen were significantly correlated
      with the independence-performance subscale of social functioning scale (SFC), and
      Reading the Mind in the Eyes test; however, the correlations do not survive
      correction for multiple comparison. The current results help to clarify the
      relationship between social functioning deficits and topological brain measures
      in schizophrenia.

PMID- 29017062
TI  - Integration of the TGx-28.65 genomic biomarker with the flow cytometry
      micronucleus test to assess the genotoxicity of disperse orange and 1,2,4
      benzenetriol in human TK6 cells.
AB  - In vitro gene expression signatures to predict toxicological responses can
      provide mechanistic context for regulatory testing. We previously developed the
      TGx-28.65 genomic biomarker from a database of gene expression profiles derived
      from human TK6 cells exposed to 28 well-known compounds. The biomarker comprises
      65 genes that can classify chemicals as DNA damaging or non-DNA damaging. In this
      study, we applied the TGx-28.65 genomic biomarker in parallel with the in vitro
      micronucleus (MN) assay to determine if two chemicals of regulatory interest at
      Health Canada, disperse orange (DO: the orange azo dye 3-[[4-[(4
      Nitrophenyl)azo]phenyl] benzylamino]propanenitrile) and 1,2,4-benzenetriol (BT: a
      metabolite of benzene) are genotoxic or non-genotoxic. Both chemicals caused dose
      dependent declines in relative survival and increases in apoptosis. A strong
      significant increase in MN induction was observed for all concentrations of BT;
      the top two concentrations of DO also caused a statistically significant increase
      in MN, but these increases were <2-fold above controls. TGx-28.65 analysis
      classified BT as genotoxic at all three concentrations and DO as genotoxic at the
      mid and high concentrations. Thus, although DO only caused a small increase in
      MN, this response was sufficient to induce a cellular DNA damage response.
      Benchmark dose modeling confirmed that BT is much more potent than DO. The
      results strongly suggest that follow-up work is required to assess whether DO and
      BT are also genotoxic in vivo. This is particularly important for DO, which may
      require metabolic activation by bacterial gut flora to fully induce its genotoxic
      potential. Our previously published data and this proof of concept study suggest
      that the TGx-28.65 genomic biomarker has the potential to add significant value
      to existing approaches used to assess genotoxicity.

PMID- 29017063
TI  - European status and perspectives on early detection and intervention in at-risk
      mental state and first episode psychosis: Viewpoint from the EPA section for
      prevention of mental disorders.

PMID- 29017064
TI  - Negative social comparisons and psychosis proneness in a healthy adolescent
      population.
AB  - There is growing evidence of an association between negative social comparisons
      (NSC) and both psychosis, and psychosis proneness. The majority of the work thus
      far, however, has focused largely on one type of NSC, namely, social rank. Whilst
      social rank is clearly an important factor, an individual's perception of
      belonging is likely also of importance; particularly, when considering
      individuals from collectivistic cultures such as China, where greater emphasis is
      placed on fitting into the group. There is also limited research investigating
      what factors may contribute towards the relationship between NSC and psychosis
      proneness, and to what extent this relationship may be due to common familial
      factors. To address these issues, we examined whether (1) Social rank and
      perceived belonging predict negative, positive and depressive psychotic
      experiences in a Chinese, adolescent, twin and sibling population, (2) coping
      styles moderate the impact of these relationships and (3), there is a familial
      association between NSC and psychosis proneness. Both social rank and perceived
      belonging were found to predict the negative and depressive dimensions of
      psychosis. These relationships were moderated by problem-focused coping styles.
      Interestingly, the association between perception of belonging, and negative
      psychotic experiences was familial-and stronger in Monozygotic twins-indicating
      perhaps shared aetiology due to common genes. Our findings highlight NSC as
      potential vulnerability markers for negative and depressive psychotic
      experiences, and suggest potentially different aetiological pathways amongst
      different NSC and different psychotic experiences. On a clinical level, our
      findings emphasize the need to consider coping styles when treating at-risk
      individuals.

PMID- 29017059
TI  - Direct Activation of BAX by BTSA1 Overcomes Apoptosis Resistance in Acute Myeloid
      Leukemia.
AB  - The BCL-2 family protein BAX is a central mediator of apoptosis. Overexpression
      of anti-apoptotic BCL-2 proteins contributes to tumor development and resistance
      to therapy by suppressing BAX and its activators. We report the discovery of
      BTSA1, a pharmacologically optimized BAX activator that binds with high affinity
      and specificity to the N-terminal activation site and induces conformational
      changes to BAX leading to BAX-mediated apoptosis. BTSA1-induced BAX activation
      effectively promotes apoptosis in leukemia cell lines and patient samples while
      sparing healthy cells. BAX expression levels and cytosolic conformation regulate
      sensitivity to BTSA1. BTSA1 potently suppressed human acute myeloid leukemia
      (AML) xenografts and increased host survival without toxicity. This study
      provides proof-of-concept for direct BAX activation as a treatment strategy in
      AML.

PMID- 29017065
TI  - Synthesis and bioelectrochemical behavior of aromatic amines.
AB  - Four aromatic amines 1-amino-4-phenoxybenzene (A1), 4-(4-aminophenyloxy) biphenyl
      (A2), 1-(4-aminophenoxy) naphthalene (A3) and 2-(4-aminophenoxy) naphthalene (A4)
      were synthesized and characterized by elemental, spectroscopic (FTIR, NMR), mass
      spectrometric and single crystal X-ray diffraction methods. The compounds
      crystallized in monoclinic crystal system with space group P21. Intermolecular
      hydrogen bonds were observed between the amine group and amine/ether acceptors of
      neighboring molecules. Electrochemical investigations were done using cyclic
      voltammetry (CV), square wave voltammetry (SWV) and differential pulse
      voltammetry (DPV). CV studies showed that oxidation of aromatic amines takes
      place at about 0.9 V (vs. Ag/AgCl) and the electron transfer (ET) process has
      irreversible nature. After first scan reactive intermediate were generated
      electrochemically and some other cathodic and anodic peaks also appeared in the
      succeeding scans. DPV study revealed that ET process is accompanied by one
      electron. DNA binding study of aromatic amines was performed by CV and UV-visible
      spectroscopy. These investigations revealed groove binding mode of interaction of
      aromatic amines with DNA.

PMID- 29017058
TI  - Androgen Receptor Pathway-Independent Prostate Cancer Is Sustained through FGF
      Signaling.
AB  - Androgen receptor (AR) signaling is a distinctive feature of prostate carcinoma
      (PC) and represents the major therapeutic target for treating metastatic prostate
      cancer (mPC). Though highly effective, AR antagonism can produce tumors that
      bypass a functional requirement for AR, often through neuroendocrine (NE)
      transdifferentiation. Through the molecular assessment of mPCs over two decades,
      we find a phenotypic shift has occurred in mPC with the emergence of an AR-null
      NE-null phenotype. These "double-negative" PCs are notable for elevated FGF and
      MAPK pathway activity, which can bypass AR dependence. Pharmacological inhibitors
      of MAPK or FGFR repressed the growth of double-negative PCs in vitro and in vivo.
      Our results indicate that FGF/MAPK blockade may be particularly efficacious
      against mPCs with an AR-null phenotype.

PMID- 29017066
TI  - A psychometric evaluation of the Posttraumatic Cognitions Inventory with Veterans
      seeking treatment following military trauma exposure.
AB  - Trauma-related beliefs have salient relationships to the development and
      maintenance of Posttraumatic Stress Disorder (PTSD) following stress exposure.
      The Posttraumatic Cognitions Inventory (PTCI) has the potential to be a standard
      assessment of this critical construct. However, some critical aspects of validity
      and reliability appear to vary by population. To date, the PTCI has not been
      psychometrically evaluated for use with military-specific traumas such as combat
      and military sexual trauma (MST). Based on exploratory and confirmatory analyses
      with 949 Veterans seeking trauma-focused treatment for military traumas, we found
      a four factor model (negative view of the self, negative view of the world, self
      blame, and negative beliefs about coping competence) provided the best fit. In
      contrast, the original three factor model was not confirmed. Both models
      demonstrated convergent and discriminative validity. Although gender was
      associated with PTCI total and factor scores, differences did not persist after
      controlling for trauma type. MST was associated with higher PTCI scores even when
      controlling for gender, though the clinical magnitude of these differences is
      likely negligible. Internal reliability validity was demonstrated with PTCI total
      and subscale scores.

PMID- 29017067
TI  - Clinically relevant response and remission outcomes in cariprazine-treated
      patients with bipolar I disorder.
AB  - BACKGROUND: Rates of response and remission are measures that endorse the
      clinical significance of treatment. Cariprazine is FDA approved for the acute
      treatment of schizophrenia and manic or mixed episodes associated with bipolar I
      disorder in adults. Post hoc analyses of pooled data from 3 pivotal trials of
      cariprazine in manic/mixed episodes associated with bipolar I disorder were
      conducted to investigate the effect of cariprazine on various criteria of
      response and remission. METHODS: The constituent studies were 3-week randomized,
      double-blind, placebo-controlled, multicenter, parallel-group phase II/III
      studies in adult patients (age 18-65 years) with bipolar I disorder (NCT00488618,
      NCT01058096, NCT01058668). Post hoc analyses included Young Mania Rating Scale
      (YMRS) outcomes for response (>=50% decrease in score), remission (total score
      <=12 and <=8), cumulative remission, and global improvement. Additionally,
      composite remission (YMRS total score <=12 plus Montgomery-Asberg Depression
      Rating Scale total score <=12) and worsening/switch to depression (MADRS total
      score >=15) by week were investigated. RESULTS: Rates of response and remission
      were significantly greater for cariprazine versus placebo on every measure
      evaluated (P < .01 all analyses); the estimated number needed to treat for each
      measure was <=10. There was no evidence of worsening/switch to depression.
      LIMITATIONS: Post hoc analyses, short treatment duration, no active comparator.
      DISCUSSION: Cariprazine-treated patients with bipolar I disorder attained
      clinically significant improvement in manic symptoms as shown by significantly
      greater rates of response and remission versus placebo; improvement in manic
      symptoms did not induce depressive symptoms.

PMID- 29017068
TI  - Allopurinol augmentation in acute mania: A meta-analysis of placebo-controlled
      trials.
AB  - BACKGROUND: Allopurinol is a xanthine oxidase inhibitor commonly used in the
      treatment of gout. Recent studies have also shown its promise as an adjunctive
      treatment for manic episodes in bipolar 1 disorder, possibly through mechanisms
      involving the purinergic pathway. However, its efficacy across studies has been
      inconsistent, so we conducted a meta-analysis of the published controlled studies
      with the goal of determining the efficacy profile of allopurinol as an adjunctive
      treatment for mania in bipolar disorder. METHODS: An online search was conducted
      using PubMed for placebo-controlled, randomized, double-blind, clinical trials
      (RCTs) using the terms "allopurinol," "bipolar," "mania," "manic," and "YMRS" and
      a meta-analysis was conducted in accordance with the Preferred Reporting Items
      for Systematic reviews and Meta-Analyses statement. RESULTS: Five studies met the
      criteria for inclusion. Three of the five studies were inpatient treatments, one
      study was outpatient treatment, and one study had a mixture of both. All studies
      used allopurinol as an adjunct in treating acute mania in bipolar disorder
      subjects. Four of the studies showed efficacy in the primary outcome measure
      between allopurinol vs. placebo groups with significantly reduced YMRS scores
      while one showed no significant effect size between the allopurinol and placebo
      groups. The overall effect size for the four studies is d = 0.294. No significant
      difference in side effects were found between groups for any of the studies.
      CONCLUSION: The data suggest that allopurinol may have some efficacy as an
      adjunct in reducing mania symptoms during acute manic episodes in patients with
      bipolar disorder. Adjunctive allopurinol efficacy may be related to the mood
      stabilizer used. Additional controlled trials with greater sample sizes,
      homogenous dosing, and consistent treatment modalities are needed to determine
      optimal clinical application.

PMID- 29017069
TI  - Comprehensive self-control training benefits depressed college students: A six
      month randomized controlled intervention trial.
AB  - BACKGROUND: Depressive disorder was associated with dysfunctional self
      regulation. The current study attempted to design and test a comprehensive self
      control training (CSCT) program with an overall emphasis on behaviral activation
      in depressed Chinese college students. METHODS: Participants included 74 students
      who had diagnosed with major depression, they were randomly assigned to one of
      the two groups: intervention group (n=37), and control group (n=37). The
      intervention participants received an eight-week CSCT and four-month follow-up
      consolidation program, as compared to the control group who received only pre
      post-and-follow-up measurements. All participants measured Beck Depression
      Inventory (BDI-II) and Self-control Scale (SCS) at three time points: baseline,
      post-training, and four-month follow-up. RESULTS: The dropout rates were 6 (8.1%)
      in the intervention group and 3 (4.1%) in the control group at the end of six
      month intervention. The general linear model repeated measures analysis of
      variance revealed that comparing with the control group, the intervention group
      participants had more increase in their trait self-control score, at the
      meantime, their depressive symptoms had significantly improved. Univariate and
      logistic regression analyses revealed that participants with milder baseline
      depressive symptoms were more likely to benefit from CSCT interventions;
      depression improvement was also associated with the number of sessions attended.
      LIMITATIONS: The main limitation was related to the small sample size which
      consisted of college students who were relatively young and well educated.
      CONCLUSIONS: The current study demonstrates that CSCT program could temporarily
      enhance self-control capacity as well as improve depressive symptoms;
      participants who are mildly to moderately depressed, and who could adhere to the
      training protocol are more likely to benefit from the intervention.

PMID- 29017070
TI  - Conducting electrospun fibres with polyanionic grafts as highly selective, label
      free, electrochemical biosensor with a low detection limit for non-Hodgkin
      lymphoma gene.
AB  - A highly selective, label-free sensor for the non-Hodgkin lymphoma gene, with an
      aM detection limit, utilizing electrochemical impedance spectroscopy (EIS) is
      presented. The sensor consists of a conducting electrospun fibre mat, surface
      grafted with poly(acrylic acid) (PAA) brushes and a conducting polymer sensing
      element with covalently attached oligonucleotide probes. The sensor was
      fabricated from electrospun NBR rubber, embedded with poly(3,4
      ethylenedioxythiophene) (PEDOT), followed by grafting poly(acrylic acid) brushes
      and then electrochemically polymerizing a conducting polymer monomer with ssDNA
      probe sequence pre-attached. The resulting non-Hodgkin lymphoma gene sensor
      showed a detection limit of 1aM (1 * 10-18mol/L), more than 400 folds lower
      compared to a thin-film analogue. The sensor presented extraordinary selectivity,
      with only 1%, 2.7% and 4.6% of the signal recorded for the fully non
      complimentary, T-A and G-C base mismatch oligonucleotide sequences, respectively.
      We suggest that such greatly enhanced selectivity is due to the presence of
      negatively charged carboxylic acid moieties from PAA grafts that
      electrostatically repel the non-complementary and mismatch DNA sequences,
      overcoming the non-specific binding.

PMID- 29017071
TI  - NMR studies of ligand binding.
AB  - NMR spectroscopy is an established tool in drug discovery, but its strength is
      commonly regarded to be largely confined to the early stages of hit discovery and
      fragment based drug design, where NMR offers unique capabilities of
      characterizing the binding modes of ligand molecules that bind sufficiently
      weakly to be in rapid exchange between bound and free state. Here we, first,
      provide a meta-review of recent reviews on NMR studies of ligand binding and,
      second, review recent progress towards NMR characterization of the ligand binding
      mode in stable protein-ligand complexes, with particular emphasis on the global
      positioning system (GPS) approach enabled by paramagnetic lanthanide tags.

PMID- 29017072
TI  - More than a feeling: The bidirectional convergence of semantic visual object and
      somatosensory processing.
AB  - Prevalent theories of semantic processing assert that the sensorimotor system
      plays a functional role in the semantic processing of manipulable objects. While
      motor execution has been shown to impact object processing, involvement of the
      somatosensory system has remained relatively unexplored. Therefore, we developed
      two novel priming paradigms. In Experiment 1, participants received a vibratory
      hand prime (on half the trials) prior to viewing a picture of either an object
      interacted primarily with the hand (e.g., a cup) or the foot (e.g., a soccer
      ball) and reported how they would interact with it. In Experiment 2, the same
      objects became the prime and participants were required to identify whether the
      vibratory stimulation occurred to their hand or foot. In both experiments,
      somatosensory priming effects arose for the hand objects, while foot objects
      showed no priming benefits. These results suggest that object semantic knowledge
      bidirectionally converges with the somatosensory system.

PMID- 29017073
TI  - Noninvasive detection of focal brain hyperthermia related to continuous epileptic
      activities using proton MR spectroscopy.
AB  - Recent studies using rat models suggested that epileptic discharges (EDs) can
      induce focal brain hyperthermia, but such ED-related hyperthermia has not been
      confirmed in humans. We examined hyperthermia of the focus of epilepsy using
      noninvasive proton magnetic resonance spectroscopy (1H-MRS) thermometry. We
      recruited six pediatric patients with refractory daily seizures, continuous
      interictal epileptic discharges, and concordant focus lesions on MRI who had
      undergone comprehensive presurgical exams. 1H-MRS thermometry calculated the
      temperatures of the presumed epileptogenic lesions, and we examined the
      contralateral counterparts in each patient as controls. As a result, the mean
      temperature of the epileptogenic foci (36.81 degrees C) was significantly higher
      than that of the controls (36.01 degrees C). The mean difference was 0.81 degrees
      C (95%CI: 0.22-1.39, p=0.017). 1H-MRS thermometry may have the ability to
      noninvasively detect focal brain hyperthermia related to continuous EDs in human
      subjects, and to contribute to a better understanding and focus detection of
      epilepsy.

PMID- 29017074
TI  - Morphological and Molecular Characterization of Aggregata spp. Frenzel 1885
      (Apicomplexa: Aggregatidae) in Octopus vulgaris Cuvier 1797 (Mollusca:
      Cephalopoda) from Central Mediterranean.
AB  - Coccidian parasites of the genus Aggregata are known to parasitize cephalopods as
      definitive hosts, however one of the genus members, A. octopiana, has shown an
      unresolved phylogeny within the same definitive host, the common octopus (Octopus
      vulgaris). Our study represents a large-scale investigation aimed at
      characterizing morphological traits and phylogeny of A. octopiana isolated from
      O. vulgaris inhabiting three distinct geographic areas of the central
      Mediterranean: The Adriatic, Ionian and Tyrrhenian Seas. The morphology of
      sporogonic stages of the parasite in octopus tissues was assessed by light and
      electron microscopy; molecular characterization has been carried out using the
      18S rRNA locus. Our results support the hypothesis that two morphologically and
      genetically different A. octopiana infect O. vulgaris in the investigated areas
      of the Mediterranean Sea. Additional nuclear and mitochondrial markers for
      Aggregata should provide further information and better resolution of its
      phylogeny.

PMID- 29017075
TI  - A simple dilute and shoot approach incorporated with pentafluorophenyl (PFP)
      column based LC-MS/MS assay for the simultaneous determination of trimethylamine
      N-oxide and trimethylamine in spot urine samples with high throughput.
AB  - Determination of trimethylamine N-oxide (TMAO) and trimethylamine (TMA) in
      biological and environmental samples has drawn great attention recently due to
      their increasing association with human health and disease. It remains a
      challenge to simultaneously quantify TMAO and TMA in a simple, fast and cost
      effective manner due to pre-analytical and analytical constraints. For the first
      time, we describe a dilute and shoot approach combined with LC-MS/MS detection
      for the simultaneous measurement of the analytes in spot urine samples with high
      throughput. Compared to the existing methods, the merits of the proposed assay
      include the use of a simple dilute and shoot approach (100-fold), small sample
      volume (10MUL), short LC run on a PFP column (4.0min) and multi-analyte MS
      detection without sample cleanup, derivatization, evaporation and a HILIC column.
      Dilution, LC and MS parameters were optimized in detail. Method validation
      yielded a wide linearity for TMAO (1.0-400MUg/mL) and TMA (0.025-10MUg/mL) with a
      respective limit of quantitation of 1.0 and 0.025MUg/mL. The quantitation was not
      affected by 41 major urinary components, structurally-related drugs and
      metabolites. The intra- and inter-day assay precisions were <=3.6% and recoveries
      were 93.3%-103.3% for spiked quality control samples. The clinical utility of the
      alternative spot urine sampling approach compared to conventional 24h urine
      collection was supported by a significant correlation between the two sampling
      strategies (n=20, p<0.0001, r=0.757-0.862; slope=0.687-1.170) and no statistical
      difference in day-to-day biological variability (n=20). The applicability and
      reliability of the assay was verified by the assessment of reference intervals in
      a cohort of 118 healthy people. The proposed assay would be beneficial for the
      rapid and accurate determination of the increasingly important TMAO and TMA
      demanded in clinical, environmental, pharmaceutical and nutritional fields.

PMID- 29017076
TI  - Determination of the phytochemical composition of Jingning fang and the in vivo
      pharmacokinetics of its metabolites in rat plasma by UPLC-MS/MS.
AB  - Jingning fang (JNF) is an effective Traditional Chinese Medicine (TCM) which is
      used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). To
      clarify the bioactive constituents of JNF, a Thermo Q ExactiveTM Plus OrbitrapTM
      mass spectrometer was used in this study. More than 127 chemical compounds were
      isolated and identified tentatively in the JNF extract, while 42 prototype
      constituents with 4 potential metabolites were identified tentatively in rat
      plasma. A method for simultaneous determination of polygalaxanthone III (PAIII),
      sibiricose A5 (A5), sibiricose A6 (A6), 3, 6'-disinapoyl sucrose (3,6'-DISS),
      tenuifoliside C (TEC), tenuifolin B (TNB), verbascoside (VCE), heterophyllin B
      (HEB) and schisandrin (SCH) in rat was developed and validated using polydatin
      (PLN) and psoralen (PSN) as internal standards. All calibration curves proved
      favorable linearity (R2>=0.9923) in linear ranges. The lower limit of
      quantification (LLOQ) was 2.5ng/mL for PAIII, A5, 3, 6'-DISS, TNB, VCE, HEB and
      SCH, 1.0ng/mL for A6 and TEC, respectively. Intra-day and inter-day precisions
      didn't exceed 14.0% for all the analytes. Extraction recoveries and matrix
      effects of analytes and IS were acceptable. The validated method has been
      successfully applied to the pharmacokinetics (PK) studies of the nine compounds
      in JNF. These findings are useful for predicting the bioactive components of JNF,
      and will aid in optimizing dose regimens of the drug.

PMID- 29017077
TI  - Intermolecular interaction in nucleobases and dimethyl sulfoxide/water molecules:
      A DFT, NBO, AIM and NCI analysis.
AB  - This study aims to cast light on the physico-chemical nature and energetics of
      interactions between the nucleobases and water/DMSO molecules which occurs
      through the non-conventional CH?O/N-H bonds using a comprehensive quantum
      chemical approach. The computed interaction energies do not show any appreciable
      change for all the nucleobase-solvent complexes, conforming the experimental
      findings on the hydration enthalpies. Compared to water, DMSO form complexes with
      high interaction energies. The quantitative molecular electrostatic potentials
      display a charge transfer during the complexation. NBO analysis shows the
      nucleobase-DMSO complexes, have higher stabilization energy values than the
      nucleobase-water complexes. AIM analysis illustrates that the in the nucleobase
      DMSO complexes, SO?H-N type interaction have strongest hydrogen bond strength
      with high EHB values. Furthermore, the Laplacian of electron density and total
      electron density were negative indicating the partial covalent nature of bonding
      in these systems, while the other bonds are classified as noncovalent
      interactions. EDA analysis indicates, the electrostatic interaction is more
      pronounced in the case of nucleobase-water complexes, while the dispersion
      contribution is more dominant in nucleobase-DMSO complexes. NCI-RDG analysis
      proves the existence of strong hydrogen bonding in nucleobase-DMSO complex, which
      supports the AIM results.

PMID- 29017078
TI  - FGF1 and IGF1-conditioned 3D culture system promoted the amplification and cancer
      stemness of lung cancer cells.
AB  - Lung cancer stem cells (LCSCs) are considered as the cellular origins of
      metastasis and relapse of lung cancer. However, routine two-dimensional culture
      system (2D-culture) hardly mimics the growth and functions of LCSCs in vivo and
      therefore significantly decreases the stemness activity of LCSCs. In this study,
      we constructed a special BME-based three-dimensional culture system (3D-culture)
      to amplify LCSCs in human lung adenocarcinoma cell line A549 cells and found 3D
      culture promoted the enrichment and amplification of LCSCs in A549 cells
      displaying higher proliferation potential and invasion activity, but lower
      apoptosis. The expression and secretion levels of FGF1 and IGF1 were dramatically
      elevated in 3D-culture compared to 2D-culture. After growing in FGF1 and IGF1
      conditioned 3D-culture, the proportion of LCSCs with specific stemness phenotypes
      in A549 cells significantly increased compared to that in conventional 3D
      suspension culture system. Further results indicated that FGF1 and IGF1 promoted
      the amplification and cancer stemness of LCSCs dependent on MAPK signaling
      pathway. Our data firstly established a growth factors-conditioned 3D-culture for
      LCSCs and demonstrated the effects of FGF1 and IGF1 in promoting the enrichment
      and amplification of LCSCs which might provide a feasible cell model in vitro for
      both mechanism study and translational research on lung cancer.

PMID- 29017080
TI  - Prognostic significance of postoperative spikes varied in different surgical
      procedures for mesial temporal sclerosis.
AB  - PURPOSE: We conducted this study to compare the occurrence and prognostic
      significance of early postoperative interictal epileptiform discharges (IEDs) on
      seizure outcomes between corticoamygdalohippocampectomy (CAH) and selective
      amygdalohippocampectomy (SAH). METHODS: We reviewed our database of patients who
      had epilepsy surgery with hippocampus atrophy or signal changes on brain MRIs and
      pathology of mesial temporal sclerosis. One hundred and seventy-seven CAH and 39
      SAH patients were enrolled. Postoperative EEG within 30days, other preoperative
      variables and seizure outcome 2years after surgery were obtained for analysis.
      Engel's IA and IB were defined as seizure-free. RESULTS: There was no significant
      difference in the seizure-free rate between the two procedures (127 (71.8%) of
      CAH vs 30 (76.9%) of SAH, p=0.51). Postoperative IEDs were more frequently seen
      in the SAH group (64.1%) than in the CAH group (29.9%), p<0.001. The IEDs in the
      SAH group did not show correlation with the seizure outcome 2 years after
      surgery. In the CAH group, patients who had no postoperative IEDs showed a higher
      seizure-free rate compared to those with IEDs (78.2% vs 56.6%, p=0.003; OR 2.267,
      95% CI 1.09-4.73, p=0.029 in multivariate logistic regression). CONCLUSIONS:
      Early postoperative IEDs are more frequently seen in SAH than in CAH. Unlike in
      patients with CAH, the presence of IEDs after SAH was not a predictor of seizure
      recurrence. The type of surgery should be considered while utilizing
      postoperative IEDs for evaluating the prognosis.

PMID- 29017079
TI  - Effects of the fibrous topography-mediated macrophage phenotype transition on the
      recruitment of mesenchymal stem cells: An in vivo study.
AB  - Host responses to a biomaterial critically influence its in vivo performance.
      Biomaterial architectures that can recruit endogenous host stem cells could be
      beneficial in tissue regeneration or integration. Here, we report that the
      fibrous topography of biomaterials promotes the recruitment of host mesenchymal
      stem cells (MSCs) by facilitating the macrophage phenotype transition from M1-to
      M2. Electrospun poly (epsilon-caprolactone) fiber (PCL-fiber) films were
      implanted into the subcutaneous tissues of rats, and the response of host cells
      to the PCL-fiber was evaluated and compared with those of solid ones (PCL-solid).
      During the initial post-implantation period, greater numbers of cells were
      recruited and adhered to the PCL-fiber compared to the PCL-solid, and the cells
      exhibited the M1 phenotype, which was supported by the enhanced adsorption of
      complement C3a to the implanted PCL-fiber. Subsequently, the PCL-fiber supported
      the macrophage phenotype transition from M1-to-M2, which was confirmed by the
      ratio of M2/M1 marker (CD163/CCR7)-positive cells and by the expression of M2/M1
      markers (arginase-1/iNOS). The PCL-fiber also reduced the formation of foreign
      body giant cells. MSC marker (CD29, CD44, and CD90)-positive cells began to
      appear as early as day 4 on the PCL-fiber, while few MSCs were observed on the
      PCL-solid. The MSCs migration ex vivo assay showed that MSCs substantially
      migrated across the trans-wells toward the implanted PCL-fiber. The cells on the
      implanted PCL-fiber expressed and secreted substantial levels of SDF-1 (CXCL-12),
      while anti-SDF-1 neutralizing antibody abrogated the MSCs migration. Taken
      together, these results provide evidence that the fibrous topography of
      biomaterials enhances the recruitment of MSCs by promoting macrophage
      recruitment, facilitating M1-to-M2 transition, and enhancing SDF-1 secretion.

PMID- 29017082
TI  - Temporal lobe surgery for intractable epilepsy in children: What to do with the
      hippocampus?
AB  - PURPOSE: Resection of the hippocampus can cause verbal memory decline, especially
      in the pediatric population. Thus, preservation of the hippocampus can be crucial
      for the quality of life of children with intractable temporal lobe epilepsy (TLE)
      who are candidates for epilepsy surgery. We investigated techniques that
      determine whether the hippocampus is part of the epileptogenic zone and the
      outcomes of pediatric surgery aimed to spare the hippocampus. METHODS: We
      accessed data of children with normal hippocampus on MRI, who underwent surgery
      for medically refractory TLE. To identify epileptogenic areas,
      electrocorticography was performed in patients with space occupying lesions
      adjacent to the hippocampus, and long term invasive monitoring in patients with
      nonlesional TLE. Postoperative seizure control was classified according to Engel
      I-IV; Class I indicates seizure-free. RESULTS: Eleven females and 11 males met
      study inclusion criteria; the mean age at surgery was 11.3 years. Cortical and
      hippocampal electrocorticography was performed in 15 patients and long term
      invasive hippocampal monitoring in seven. The hippocampus was preserved in 16
      patients (73%) while hippocampectomy was performed in 6 (27%). At the end of a
      mean follow-up of 3.5 years, 94% (15/16) of the patients who did not undergo
      hippocampectomy were classified as Engel I, compared to 50% (3/6) who underwent
      hippocampectomy. CONCLUSION: Sparing the hippocampus in temporal lobe epilepsy
      surgery is possible with excellent seizure outcome, while using the proper
      intraoperative technique.

PMID- 29017083
TI  - Social workers' views on pre-trial therapy in cases of child sexual abuse in
      South Africa.
AB  - This study sought to explore anecdotal reports that social workers in South
      Africa are often advised to postpone therapy with child complainants of sexual
      abuse until after the child's testimony, based on concerns of legal professionals
      that therapeutic interventions could influence the child's testimony. Applying
      purposive sampling and a qualitative research study, individual and focus group
      interviews were conducted with 18 social workers and one psychologist that
      provide therapeutic services to child complainants of sexual abuse in the Gauteng
      province. Interviews were audio-recorded, transcribed and independently analyzed
      by both researchers, performing thematic analysis. Emerging themes include a lack
      of directives in terms of the provision of pre-trial therapy for child victims of
      sexual abuse, current practices and challenges in this regard. Recommendations
      for the way forward are presented. Limitations and future research will be
      discussed.

PMID- 29017081
TI  - Safety of intravenous lacosamide in critically ill children.
AB  - PURPOSE: Acute seizures are common in critically ill children. These patients
      would benefit from intravenous anti-seizure medications with few adverse effects.
      We reviewed the usage and effects of intravenous lacosamide in critically ill
      children with seizures or status epilepticus. METHODS: This retrospective series
      included consecutive patients who received at least one dose of intravenous
      lacosamide from April 2011 to February 2016 in the pediatric intensive care unit
      of a quaternary care children's hospital, including patients with new lacosamide
      initiation and continuation of outpatient oral lacosamide. Dosing and prescribing
      practices were reviewed. Adverse effects were defined by predefined criteria, and
      most were evaluated during the full admission. RESULTS: We identified 51
      intensive care unit admissions (47 unique patients) with intravenous lacosamide
      administration. Lacosamide was utilized as a third or fourth-line anti-seizure
      medication for acute seizures or status epilepticus in the lacosamide-naive
      cohort. One patient experienced bradycardia and one patient experienced a rash
      that were considered potentially related to lacosamide. No other adverse effects
      were identified, including no evidence of PR interval prolongation. CONCLUSIONS:
      Lacosamide was well tolerated in critically ill children. Further study is
      warranted to evaluate the effectiveness of earlier lacosamide use for pediatric
      status epilepticus and acute seizures.

PMID- 29017084
TI  - Disseminated adenovirus infection after allogeneic stem cell transplant and the
      potential role of brincidofovir - Case series and 10 year experience of
      management in an adult transplant cohort.
AB  - BACKGROUND: Adenovirus infection is a recognized complication following
      haematopoietic stem cell transplantation. We present a review of our experience
      of these infections in our transplant cohort over 10 years including 3 patients
      treated with the novel antiviral brincidofovir. OBJECTIVES: We aimed to describe
      the presentation, response to treatment and outcomes of adult stem cell
      transplant patients with disseminated adenovirus infection. STUDY DESIGN: All
      adult cases of disseminated adenovirus infection following haematopoietic stem
      cell transplant in our unit between 2005 and 2015 were identified. Transplant
      details and data on timing of diagnosis, course of infection, viral co-infection
      and treatment were collected. RESULTS: Of 733 patients transplanted, 10 patients
      had disseminated infection, including 4 male and 6 female patients with median
      age of 36.5 (range 19-59) years. 6/10 received an allograft from an unrelated
      donor. Median post-transplant time to detection of viraemia was 67days (range 20
      1140days). Median peak viral load was 3133 copies/ml (352-11,000,000) in
      survivors received cidofovir alone, one cidofovir then brincidofovir and two
      brincidofovir alone. 8/10 p and 1,580,000 copies/ml (41,999-3,000.000) in those
      who died. Five patientsatients had a decrease in viral load following antivirals
      and/or reduction in immunosuppression including all on brincidofovir. Three died
      on treatment. CONCLUSIONS: Disseminated adenovirus infection is uncommon in adult
      transplant patients and uncertainties remain surrounding effective treatment. In
      our cohort, brincidofovir has shown promise in treatment of adenoviral infection.
      However, randomized controlled studies are required to confirm this impression.

PMID- 29017085
TI  - Diseases of the pancreas and suicide mortality: A nationwide nested case-control
      study among patients with mental health disorders in Taiwan.
AB  - OBJECTIVE: Diseases of the pancreas, especially pancreatitis, have been
      implicated as possible risk factors for psychiatric illnesses, such as depression
      and anxiety disorder. This nested case-control study aimed to investigate the
      association between diseases of the pancreas and completed suicide in a
      psychiatric population-based study. METHODS: The case group comprised 6568
      completed suicides (ICD-9: E950-E959, E980-989) patients from the national
      mortality database between January 1, 2002 and December 1, 2010. These cases were
      compared with 6568 gender-, age-, residence-, and insurance premium-matched
      controls. Both suicide and non-suicide study patients were drawn from a group
      with previous psychiatric diagnoses. The risk of suicide among patients with
      diseases of the pancreas was analyzed using a conditional logistic regression
      model that controlled for alcohol-related disorder, drug dependence,
      schizophrenia, depressive disorder, bipolar disorder, anxiety disorder, Charlson
      comorbidity score, and outpatient visits. RESULTS: Disease of the pancreas was an
      independent risk factor for psychiatric patients who had completed suicide when
      adjusted for clinical and other comorbid factors. Among these covariates, alcohol
      related disorders partially mediate the suicide risk among patients with disease
      of the pancreas, and mental disorders may not mediate this suicide risk.
      CONCLUSIONS: Diseases of the pancreas were associated with increased risk of
      completed suicide after controlling for potential confounding factors.

PMID- 29017086
TI  - Dose-dependent mortality involving convulsions due to subarachnoid Urografin(r)
      injection in rats.
AB  - An ionically hypertonic contrast medium Urografin(r) was inadvertently
      administered into the subarachnoid space of an individual and this resulted in
      convulsions and acute respiratory failure. We examined the effects of
      subarachnoid Urografin(r) injections on the rat central nervous system. The onset
      and frequency of the convulsions, as well as fatality, were dependent on the
      amount of Urografin(r) administered. No convulsions were observed in rats
      receiving injections of hypertonic NaCl solution or saline. The results confirmed
      that subarachnoid injections of Urografin(r) cause convulsions and death, as
      previously reported in human cases, and our study ascertained the causal
      relationship between the above malpractice and fatal outcomes.

PMID- 29017087
TI  - Detection of butane gas inhalation at 16days after hypoxic encephalopathy: A case
      report.
AB  - In Japan, there are increasing reports of death by poisoning following butane
      abuse. To determine the specific cause of death in such cases, it is important to
      confirm the presence of fuel gas components in the body, although careful
      analysis is required because of their volatile properties. In most reported
      cases, the subject died suddenly during or immediately after butane aspiration.
      Thus, the butane concentration in the samples from the deceased should be
      relatively high. Herein, we present a case of an 18-year-old man found with
      cardiopulmonary arrest, who then exhibited hypoxic encephalopathy for 16days in a
      hospital. At autopsy, we detected hypoxic encephalopathy, pneumonia, and ischemia
      reperfusion injury of the myocardium, while the cause of cardiac arrest remained
      unclear. Toxicological analysis was then performed for fuel gas components in
      several specimens collected at autopsy. Results showed that n-butane and
      isobutane were detected in the adipose tissue at 16days after inhalation,
      indicating a role of butane gas inhalation as the cause of death. These data
      suggest that adipose tissue may be the most appropriate analysis sample to be
      collected at postmortem in cases where involvement of volatile and fat-soluble
      gas inhalation is suspected.

PMID- 29017088
TI  - Anterior cingulate cortex sulcation and its differential effects on conflict
      monitoring in bilinguals and monolinguals.
AB  - The role of the anterior cingulate cortex (ACC) in modulating the effect of
      bilingual experience on cognitive control has been reported at both functional
      and structural neural levels. Individual differences in the ACC sulcal patterns
      have been recently correlated with cognitive control efficiency in monolinguals.
      We aimed to investigate whether differences of ACC sulcation mediate the effect
      of bilingualism on cognitive control efficiency. We contrasted the performance of
      bilinguals and monolinguals during a cognitive control task (i.e., the Flanker
      Task) using a stratification based on the participants' ACC sulcal features. We
      found that performance of the two groups was differentially affected by ACC
      sulcation. Our findings provide the first evidence that early neurodevelopmental
      mechanisms may modulate the effect of different environmental backgrounds - here,
      bilingual vs monolingual experience - on cognitive efficiency.

PMID- 29017090
TI  - Combinatory effects of low concentrations of 17alpha-etinylestradiol and
      citalopram on non-reproductive behavior in adult zebrafish (Danio rerio).
AB  - Sewage effluents contain pharmaceuticals, personal care products and industrial
      chemicals, exposing aquatic organisms to complex mixtures. The consequences of
      exposure to combinations of different classes of drugs in fish are largely
      unknown. In this study, we exposed adult zebrafish (Danio rerio) males and
      females for two weeks to low, environmentally relevant concentrations of the
      endocrine disrupting chemical 17alpha-etinylestradiol (EE2) and the selective
      serotonin re-uptake inhibitor (SSRI) citalopram, alone and in combination, and
      analyzed behaviors of importance for population fitness, scototaxis (light/dark
      preference), the novel tank test and shoal cohesion. Control water contained
      0.4ng/L EE2 and the measured exposure concentrations were 0.9ng/L EE2 (nominal
      0.1) and 1ng/L EE2 (nominal 0.5). The measured concentrations of citalopram were
      0.1 (nominal 0.1) and 0.4MUg/L (nominal 0.5). Both EE2 exposures increased
      anxiety in males in the scototaxis test, with significantly longer latency
      periods before entering and fewer visits to the white zone of the tank. The
      combined exposures (0.9ng/L EE2+0.1MUg/L citalopram and 1ng/L EE2+0.4MUg/L
      citalopram) resulted in abolishment of effects of EE2, with shorter latency
      period and more transitions to white than for fish exposed to EE2 alone. In the
      novel tank test, the results surprisingly indicated lower anxiety after both EE2
      and citalopram exposure. Significantly more transitions to the upper half of the
      tank observed in males exposed to 0.1MUg/L citalopram alone compared to control
      males. Males exposed to EE2 (0.9ng/L) had shorter latency period to the upper
      half. Combination exposure resulted in a longer latency and fewer transitions to
      the upper half compared to both control, EE2- and citalopram-exposed males. Males
      exposed to the combination spent significantly less time in the upper half than
      males EE2 or citalopram-exposed males. Females exposed to 1ng/L EE2 had fewer
      transitions to the upper half than the control group and females exposed to
      0.4MUg/L citalopram. In the shoaling test, males exposed to 0.1MUg/L
      citalopram+0.9ng/L EE2 showed more transitions away from peers than males exposed
      to 0.1MUg/L citalopram alone. In conclusion, low concentrations of EE2, closely
      above the predicted no effect concentration (NOEC) of 0.1ng/L, created anxiety
      like behavior in zebrafish males. Citalopram showed marginal effects at these low
      concentrations but in the combination exposure the behavioral effects of EE2 were
      abolished. This is an initial effort to understand the effects of cocktails of
      anthropogenic substances contaminating aquatic environments.

PMID- 29017089
TI  - Reduced interhemispheric executive control network coupling in men during early
      cocaine abstinence: A pilot study.
AB  - BACKGROUND: Individuals who use cocaine have fewer cognitive resources needed to
      maintain abstinence. This is evidenced by blunted brain function during cognitive
      control tasks and reduced communication between brain regions associated with
      cognitive function. For instance, relapse vulnerability is heightened in
      individuals with less communication between the right and left frontoparietal
      executive control network (ECN). Given that recent cocaine use enhances such
      communication, it is plausible that recency of cocaine use influences
      interhemispheric ECN communication. However, it is unclear whether ECN
      communication weakens over the course of early cocaine abstinence, which may then
      enhance relapse risk. METHODS: In ten men with cocaine use disorder, we conducted
      a preliminary assessment of the relationship between the number of days since
      last cocaine use (1-3days) and interhemispheric ECN coupling using resting state
      functional magnetic resonance imaging (fMRI). RESULTS: Reduced interhemispheric
      ECN coupling was associated with increasing days since last cocaine use; weaker
      coupling was also associated with lower urine cocaine metabolite concentrations.
      This association was more prominent in prefrontal than parietal ECN-subregions.
      CONCLUSIONS: Preliminary results indicate that resting state interhemispheric ECN
      coupling weakens within the first few days following last cocaine use. Because of
      the known link between reduced ECN interhemispheric coupling and relapse
      vulnerability, these results suggest that relapse risk may increase the longer an
      individual abstains during an early quit attempt. Treatments focused on reversing
      this coupling deficit may facilitate abstinence.

PMID- 29017091
TI  - The regulation of cell polarity by lipid transfer proteins of the SEC14 family.
AB  - SEC14 lipid transfer proteins are important regulators of phospholipid
      metabolism. Structural, genetic and cell biological studies in yeast suggest that
      they help phosphatidylinositol (PtdIns)/phosphoinositide (PIP) kinases to
      overcome their intrinsic inefficiency to recognize membrane-embedded substrate,
      thereby playing a key role in PIP homeostasis. Genomes of higher plants encode a
      high number and diversity of SEC14 proteins, often in combination with other
      domains. The Arabidopsis SEC14-Nlj16 protein AtSFH1, an important regulator of
      root hair development, plays an important role in the establishment of PIP
      microdomains. Key to this mechanism is a highly specific interaction of the Nlj16
      domain with PtdIns(4,5)P2 and an interaction-triggered oligomerization of the
      protein. Nlj16/PtdIns(4,5)P2 interaction depends on a polybasic motif similar to
      those identified in other regulatory proteins.

PMID- 29017092
TI  - The need for accuracy and validity in research on nightlife and drinking: A
      commentary on Devilly et al. and recommendations for future research.
AB  - Research on nightlife and drinking faces many unique challenges, and validity in
      research is an important concern. A recent publication by Devilly et al. entitled
      "SmartStart: Results of a large point of entry study into preloading alcohol and
      associated behaviours" contains definitions and assumptions about prior work that
      require more careful consideration. Important issues include: using a definition
      of pre-drinking which is the same as previous work so that valid comparison can
      be made, reporting of blood alcohol concentration (BAC) levels that comply with
      other work, accurate reporting of response rates, and careful consideration of
      sampling approaches to maximise ethical integrity. Ensuring consistency of
      definition and accurate representation of previous literature regarding BAC, pre
      drinking and energy drink use, is important for supplying the broader community
      with reliable information on which policy decisions can be made.

PMID- 29017093
TI  - Personality pathology and intentional self-harm: cross-cutting insights from
      categorical and dimensional models.
AB  - This paper reviews current literature on the links between personality pathology
      and intentional self-harm, including nonsuicidal self-injury (NSSI) and suicidal
      behaviors. Specifically, this review highlights recent advances stemming from
      longitudinal, epidemiological, and health registry studies, as well as emerging
      research on pathological personality traits and intentional self-harm, and
      integrates current knowledge across dimensional and categorical frameworks to
      provide recommendations for clinical practice and future research. This review
      provides strong evidence that personality disorders marked by intense and
      unstable negative affect, detachment/low extraversion, aggression/hostility, and
      specific facets of impulsivity may be considered risk factors for suicidal
      behaviors. Further, there is some evidence of a stronger relation between
      maladaptive personality traits and suicidal versus non-suicidal intentional self
      harm.

PMID- 29017094
TI  - Quantifying catastrophic and climate impacted hazards based on local expert
      opinions.
AB  - Quantifying the potential costs of catastrophic and climate impacted hazards is a
      challenging but important exercise as the occurrence of such events is usually
      associated with high damage and uncertainty. At the local level, there is often a
      lack of information on rare extreme events, which means that the available data
      is not sufficient to fit a distribution and derive parameter values for frequency
      and severity distributions. This paper discusses the use of local assessments of
      extreme events and utilises expert elicitation in order to obtain values for
      distribution parameters that will feed into management decisions with regards to
      quantifying catastrophic risks. We illustrate a simple approach, where a local
      expert is required to only specify two percentiles of the loss distribution in
      order to provide an estimate for the severity distribution of climate impacted
      hazards. In our approach we use heavy-tailed distributions to capture the
      severity of events. Our method allows local government decision makers to focus
      on extreme losses and the tail of the distribution. An illustration of the method
      is provided utilising an example that quantifies property losses from bushfires
      for a local area in northern Sydney. We further illustrate how key variables,
      such as discount rates, assumptions about climatic change and adaptation
      measures, will impact the estimates of losses.

PMID- 29017095
TI  - Persistence and reduction of Shiga toxin-producing Escherichia coli serotype
      O26:H11 in different types of raw fermented sausages.
AB  - Fermented sausages have been identified as source of several outbreaks of Shiga
      toxin-producing Escherichia coli (STEC). Illnesses linked to non-O157 STEC
      serotypes appear to be on the rise worldwide, and serogroup O26 is the second
      most reported in Europe after O157. However, data on the behavior of serogroup
      O26 in food are rare, so that the aim of this study was to investigate the
      survival of STEC O26:H11 in different types of fermented sausages ("Teewurst",
      fast-ripened and long-fermented salami). Challenge studies were performed with an
      inoculation cocktail which consisted of three STEC O26:H11 strains isolated from
      human, cattle and food sources. In the short-ripened spreadable sausage type
      "Teewurst" STEC counts decreased by only 0.5 log10 within 28days. In contrast,
      STEC reductions from 2.2 to 2.6 log10 units were observed in the different salami
      products, while the most pronounced decrease of 1.0 log10 unit within one day was
      detected in fast-ripened sausages with glucono delta-lactone (GdL). Moreover,
      numbers of the food-associated E. coli O26:H11 strain were significantly higher
      (p<0.001) than those of the human and cattle STEC O26:H11 strains in all types of
      fermented sausages. Approximately 60% of all STEC isolates from GdL salami shared
      the genotypic virulence profile of the food-associated E. coli O26:H11 strain. In
      summary, hurdles of acidification and drying during salami ripening resulted in
      reductions of STEC O26:H11 counts. However, our results also indicate that STEC
      O26:H11 can persist in the environment of "Teewurst" and might therefore pose a
      risk to public health.

PMID- 29017096
TI  - Enhancing miR-132 expression by aryl hydrocarbon receptor attenuates
      tumorigenesis associated with chronic colitis.
AB  - BACKGROUND: Chronic inflammation in ulcerative colitis (UC) patients is the major
      risk factor for colitis-associated colon cancer (CAC). Recent evidences have
      shown that microRNAs (miRNAs) are implicated in CAC pathogenesis. However, the
      interaction of miRNAs with the transcription factors that alleviate CAC has not
      been reported. METHODS: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 3,3'
      diindolylmethane (DIM) were used to activate aryl hydrocarbon receptor (Ahr) in
      azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CAC in mice. Real-time
      PCR was used to quantify the mRNAs of miRNA and coding genes while western blot
      and ELISA were used to quantify protein levels. Silencing miRNA was carried out
      by means of electroporation and locked nucleic acid (LNA)-miRNA. RESULTS:
      Inducing CAC in mice upregulated miR-132 expression in the colon, spleen and
      lymph nodes at all stages of disease development. Activation of Ahr by TCDD or
      DIM boosted miR-132 expression and alleviated CAC severity by suppression of
      macrophage infiltration and pro-inflammatory cytokines. Interestingly, TCDD, but
      not DIM, augmented a cholinergic anti-inflammation by inducing
      acetylcholinesterase (AChE)-targeting miR-132. This anti-inflammation was
      manifested by suppressed production of TNF-alpha, IL-1beta and IL-6. Silencing
      miR-132 in vivo in TCDD-treated mice abrogated the cholinergic anti-inflammation
      and exacerbated CAC. In addition, inhibition of miR-132 in vitro in CD4+ cells
      and macrophages mitigated the inhibitory effect of TCDD on AChE catalytic
      activity. CONCLUSION: Our findings identify miR-132 as a new molecule implicated
      in CAC pathogenesis, and reveal that miR-132 mediates the ameliorating effects of
      TCDD on CAC, suggesting miR-132 as a promising therapeutic candidate to control
      autoimmune inflammation and tumorigenesis in CAC patients.

PMID- 29017097
TI  - Graphene oxide assisted template-free synthesis of nanoscale splode-like NiCo2O4
      hollow microsphere with superior lithium storage properties.
AB  - A facile template-free Ostwald ripening method is developed for the preparation
      of the reduced graphene oxide supported splode-like NiCo2O4 hollow microsphere
      (SNHM/rGO). The graphene oxide used in the reaction mixture is found to play a
      crucial role in the formation of the SNHM/rGO. It promotes the formation of the
      NiCo-glycerol microspheres suitable for the Ostwald ripening to form the reduced
      graphene oxide supported hollow NiCo-glycerol microspheres, which is important
      for the subsequent calcination to form the SNHM/rGO. The obtained SNHM/rGO shows
      a great promise as the anode for lithium-ion batteries and can deliver a stable
      reversible capacity of 1048.1 mA h g-1 at the current density of 100 mA g-1. The
      performance of the SNHM/rGO is much higher than that of most NiCo2O4-based
      materials reported previously, strongly suggesting that the SNHM/rGO could be
      used as the anode for practical applications. This is well supported by the
      higher performance of the LiCoO2//SNHM-rGO full cell. The excellent
      electrochemical performance can be attributed to the specific structure of the
      SNHM/rGO, which comprises the splode-like hollow NiCo2O4 microspheres with the
      reduced graphene oxide integrated.

PMID- 29017098
TI  - Self-assembled Ti3C2Tx/SCNT composite electrode with improved electrochemical
      performance for supercapacitor.
AB  - Two-dimensional titanium carbide has gained considerable attention in recent
      years as an electrode material for supercapacitors due to its high melting point,
      good electrical conductivity, hydrophilicity and large electrochemically active
      surfaces. However, the irreversible restacking during synthesis restricts its
      development and practical applications. Here, Ti3C2Tx/SCNT self-assembled
      composite electrodes were rationally designed and successfully synthesized by
      introducing single-walled carbon nanotubes (SCNTs) as interlayer spacers to
      decrease the restacking of the Ti3C2Tx sheets during the synthesis process. SCNTs
      can not only increase the specific surface area as well as the interlayer space
      of the Ti3C2Tx electrode, but also increase the accessible capability of
      electrolyte ions, and thus it improved the electrochemical performance of the
      electrode. The as-prepared Ti3C2Tx/SCNT self-assembled composite electrode
      achieved a high areal capacitance of 220mF/cm2 (314F/cm3) and a remarkable
      capacitance retention of 95% after 10,000cycles.

PMID- 29017099
TI  - Co-adsorption and sequential adsorption of the co-existence four heavy metal ions
      and three fluoroquinolones on the functionalized ferromagnetic 3D NiFe2O4 porous
      hollow microsphere.
AB  - Functionalized magnetic microsphere NiFe2O4 (MS-NiFe2O4) with a 3D hierarchical
      porous hollow structure was fabricated using urea as the modifier and soft
      templates by a simple one-pot solvothermal method. The constructed MS-NiFe2O4
      shows excellent dual functions which can not only undergo simultaneous rapid
      removal of the co-existence metal ions (Cu2+, Cd2+, Cr3+ and Zn2+ ions), but also
      availably adsorb fluoroquinolone (FQs) (ciprofloxacin (CIP), enrofloxacin (ENR)
      and norfloxacin (NOR)), and is easily recycled using an external magnetic field.
      The removal efficiency of eight targets could all reach up to 80% within 60min at
      pH 5. The independent adsorption of single contaminants, the competitive
      adsorption of multiple heavy metal ions/organic contaminants, the simultaneous
      and sequential adsorption of the co-existence of inorganic and organic
      contaminants onto MS-NiFe2O4 were explored in detail. Competition adsorption
      occurred between the same type of contaminants. For different types of
      contaminants, four metal ions did not affect the adsorption of the other three
      FQs in the sequential and simultaneously adsorption system, and vice versa. The
      possible adsorption mechanism between targets and MS-NiFe2O4 was revealed.

PMID- 29017100
TI  - Enhanced formation of hydroxyapatites in gelatin/imogolite macroporous hydrogels.
AB  - HYPOTHESIS: Gelatin is widely investigated for the fabrication of synthetic
      scaffolds in bone tissue engineering. Practical limitations to its use are mainly
      due to the fast dissolution rate in physiological conditions and to the lack of
      pores with suitable dimensions for cell permeation. The aim of this work is to
      exploit imogolite clays as nucleation sites for the growth of calcium phosphates
      in gelatin-based hydrogels and to take advantage of a cryogenic treatment to
      obtain pores of ~100um. EXPERIMENTS: We evaluated the effect of imogolites and a
      biocompatible cross-linker on the gelatin network in terms of morphology, thermal
      and rheological behavior. The hydrogels were cryogenically-treated and
      characterized to investigate the modification of the polymer network, both at the
      micro- and nano-scale. The samples were mineralized to investigate the effect of
      imogolites on the formation of calcium phosphates. FINDINGS: The interaction
      between gelatin, imogolite and cross-linker leads to the modification of the
      hydrogel structure at the micro-scale, while minor effects are detected at the
      nano-scale. The cryogenic procedure is successful in generating pores with the
      desired size, while the presence of imogolites in the hydrogel promotes
      hydroxyapatites formation. These results demonstrate that imogolites can be
      effectively employed as functional fillers in polymer-based scaffolds.

PMID- 29017101
TI  - Facile synthesis of novel calcined magnetic orange peel composites for efficient
      removal of arsenite through simultaneous oxidation and adsorption.
AB  - Increasing exposure to arsenic (As) contaminated ground water has become a global
      health hazard to humanity. Suitable adsorbent for As removal from water,
      especially for As(III) than As(V), is an urgent but still a challenging task. In
      this study, waste orange peel (OP) was modified with magnetic nanoparticles
      followed by calcination as a novel adsorbent and investigated for instantaneous
      oxidation and adsorption of As(III) from aqueous solutions. The batch adsorption
      experimental results showed that calcined magnetic orange peel composites (CMOPC)
      exhibited superior As(III) adsorption capacity (10.3mg/g) as compared to similar
      cost effective adsorbents due to its high surface area, large pore size and
      greater numbers of active sites on its surface. The adsorption equilibrium data
      obeyed Langmuir model, and kinetic data was well described by the pseudo-second
      order model. The adsorption mechanisms for As(III) might be involved ligand
      exchange of the hydroxyl in CMOPC to form Fe-O-As(III), and partial As(III)
      oxidation to As(V) followed by instantaneous adsorption on surface of CMOPC. The
      developed adsorbent has also demonstrated good anti-interference ability to co
      existing ions, admirable regeneration ability and pronounced capacity in treating
      simulated real As(III) contaminated water. This study revealed that waste orange
      peel, after simple treatment could be used as a potential adsorbent for As(III)
      from aqueous solutions.

PMID- 29017102
TI  - Carnitine alkyl ester bromides as novel biosourced ionic liquids, cationic
      hydrotropes and surfactants.
AB  - HYPOTHESIS: In contrast to anionic and nonionic amphiphilic substances, bio-based
      cationic ones are very rare. Cationic amphiphiles are mostly based on quaternary
      ammonium, pyridinium or imidazolium groups that are either badly biodegradable or
      have toxic residues even after degradation. In the search for green alternatives
      to cationic hydrotropes and amphiphiles, natural l-carnitine could be a promising
      candidate for a cationic headgroup. EXPERIMENTS: By esterification of carnitine
      in one step and with low cost, cationic molecules with alkyl chain length of n=2
      14 could be obtained. Their thermal properties, aggregation behaviour and
      cytotoxicity were determined. Hydrophobic compounds were solubilized in their
      aqueous solutions and the PIT-slope method was applied to determine a relative
      hydrophilicity. FINDINGS: It was found that some pure carnitine ester bromides
      were liquid at room temperature and thus can be classified as ionic liquids. They
      are highly water-soluble, and in aqueous solutions, they showed hydrotrope or
      surfactant behaviour depending on their alkyl chain length. Their high
      hydrotropic efficiency was demonstrated by solubilizing Disperse Red 13, while
      also biomolecules, like vanillin, could be dissolved in reasonable amounts. In
      all tests, they performed at least as good as the tested reference substances,
      while showing similar cytotoxicity towards human skin keratinocytes, thus
      demonstrating their potential as green functional amphiphilic molecules of
      positive charge.

PMID- 29017103
TI  - Assessing the efficiency of imidazolium-based ionic liquids on the phase behavior
      of a synthetic biomedical thermoresponsive polymer.
AB  - HYPOTHESIS: Temperature-responsive polymers (TRPs) with a phase transition
      temperature close to human physiological body temperature have attracted much
      attention in biomedical and pharmaceutical fields. Addition of small amount of
      cosolvent to TRPs is expected to influence the molecular interactions, thereby
      affecting the phase transition temperature of TRPs. Hence, it is possible to tune
      the phase behavior of TRPs and also drive transitions in TRPs by variation of
      chemical structure of cosolvent. EXPERIMENTS: To elucidate the conformational
      changes of the phase transition of TRP aqueous solution in ionic liquids (ILs),
      poly(N-vinylcaprolactam) (PVCL), a well known TRP was synthesized by solution
      polymerization. The lower critical solution temperature (LCST) behavior of
      polymer aqueous solution, with the addition of imidazolium-based ILs possessing
      same Cl- anion and a set of cations [Cnmim]+ such as 1-ethyl-3-methylimidazolium
      ([Emim]+), 1-butyl-3-methylimidazolium ([Bmim]+), 1-hexyl-3-methylimidazolium
      ([Hmim]+), 1-decyl-3-methylimidazolium ([Dmim]+), 1-allyl-3-methylimidazolium
      ([Amim]+) and 1-benzyl-3-methylimidazolium ([Bzmim]+), was monitored by using
      various sophisticated experimental techniques. FINDINGS: The modulations on the
      LCST of PVCL aqueous solutions follow the order of
      [Emim][Cl]<[Amim][Cl]<[Bmim][Cl]<[Hmim][Cl]<[Bzmim][Cl]<[Dmim][Cl]. This order
      shows that the LCST value increase with increasing the alkyl chain length of
      cation from [Emim]+ to [Dmim]+ of IL. To the best of our knowledge, this is the
      first report on comprehensive unequivocal evidence of the phase transition
      behavior of PVCL in presence of imidazolium-based ILs.

PMID- 29017104
TI  - Shift of monocyte subsets along their continuum predicts cardiovascular outcomes.
AB  - BACKGROUND AND AIMS: Distribution of monocyte subsets has been shown to predict
      cardiovascular outcomes. However, monocytes form a continuum and categorization
      into discrete subsets may be an oversimplification. We herein aimed at
      establishing whether distribution of monocytes based on CD14 and CD16
      fluorescence intensity provides incremental and complementary information on
      cardiovascular outcomes beyond enumeration of traditional subsets. METHODS: A
      cohort of 227 patients at high cardiovascular risk was characterized at baseline
      and followed for a median of 4 years. We quantified monocytes subsets by flow
      cytometry based on CD14 and CD16 expression and evaluated the continuous
      distribution of CD14 and CD16 fluorescence within each subset. RESULTS: A
      consistent shift toward higher CD16 fluorescence intensity within each monocyte
      subset was observed in patients with type 2 diabetes, despite no change in their
      frequencies. Patients with coronary artery disease (CAD) at baseline showed a
      doubling of CD14++CD16+ intermediate monocytes and a shift of non-classical and
      classical monocytes towards intermediates ones. During follow-up, cardiovascular
      death or cardiovascular events occurred in 26 patients, who showed monocyte
      skewing similar to those of patients with baseline CAD. In fully adjusted Cox
      proportional hazard regression models, higher CD16 expression on classical
      monocytes, but not the level of intermediate monocytes or other subsets,
      independently predicted adverse cardiovascular outcomes. CONCLUSIONS: Shift of
      monocyte subsets along the CD14/CD16 continuum, more than their frequencies,
      predicted adverse cardiovascular outcomes. This finding illustrates how the
      concept of monocyte continuum can be used to model the cardiovascular risk.

PMID- 29017105
TI  - Transcranial color-coded duplex sonography for evaluation of midline-shift after
      chronic-subdural hematoma evacuation (TEMASE): A prospective study.
AB  - OBJECTIVE: The incidence of chronic Subdural hematoma (cSDH) is increasing and
      its rate of recurrence varies from 5 to 33%. A postoperative brain midline-shift
      (MLS) on computed tomography (CT) equal or larger than 5mm is a risk factor for
      recurrence. Transcranial color-coded duplex sonography (TCCDS) is a noninvasive
      bedside reproducible technique useful to detect MLS. The aim of our study was to
      compare in patients affected by cSDH, the values of MLS obtained pre- and post
      operatively by TCCDS and brain CT. PATIENTS AND METHODS: 32 patients affected by
      cSDH entered the study between July 2016 and January 2017. MLS values obtained by
      TCCDS and brain CT were compared using Bland-Altman plot and linear regression
      analysis. Using the same techniques we also explored if the agreement between the
      two imaging modes was comparable in pre- and post-operative data pairs. RESULTS:
      64 data pairs of MLS values obtained by TCCDS and CT were analysed. Bland-Altman
      diagrams did not show any systematic bias of the data and linear regression
      indicated a significant correlation between the two measures both before and
      after hematoma evacuation. CONCLUSION: In patients affected by cSDH, MLS values
      obtained before and after surgery by TCCDS are comparable to those obtained by
      CT; TCCDS might be considered an alternative to CT scan in the management of
      patients after cSDH evacuation. We suggest that close clinical bedside
      examination and TCCDS might be appropriate for the post-operative management of
      cSDH, reserving CT scan only to patients with overt clinical deterioration and/or
      increasing MLS.

PMID- 29017106
TI  - Surgical outcomes after laminoplasty for cervical spondylotic myelopathy: A focus
      on the dynamic factors and signal intensity changes in the intramedullary spinal
      cord on MRI.
AB  - OBJECTIVE: We aimed to analyze the relationship between the dynamic factors and
      signal intensity changes in the intramedullary spinal cord on MRI, and surgical
      outcomes, following double-door laminoplasty for cervical spondylotic myelopathy
      (CSM). PATIENTS AND METHODS: This retrospective study included 100 consecutive
      patients who underwent double-door laminoplasty for CSM. The following factors
      were analyzed: JOA score recovery rate, age, duration from onset to surgery,
      intraoperative bleeding, signal intensity changes in the intramedullary spinal
      cord on MRI, pre and postoperative C2-7 lordotic angle (LA), changes in C2-7 LA,
      pre and postoperative C2-7 range of motion (ROM), and pre and postoperative
      segmental ROM. The Charlson Comorbidity Index (CCI) was also used for the
      assessment of complications. RESULTS: Age, CCI, preoperative segmental ROM, and
      pre and postoperative MRI grade significantly correlated with JOA score recovery
      rate (P<0.01), whereas number of expanded laminae, duration from onset to
      surgery, surgery time, intraoperative bleeding, preoperative and postoperative C2
      7 LA, change in C2-7 LA, and preoperative C2-7 ROM did not. Multivariate analysis
      showed that the preoperative segmental ROM (OR=-0.988, P=0.017) and preoperative
      MRI grade (OR=-7.170, P=0.042) were significantly associated with JOA score
      recovery rate. CONCLUSION: Considering the dynamic factors, there was no
      correlation with C2-7 ROM and surgical outcome, but preoperative segmental ROM
      and a change in signal intensity of the intramedullary spinal cord on MRI were
      negatively correlated with surgical outcome. From these results, we suggest that
      preoperative segmental ROM is possibly associated with spinal cord damage due to
      repeated minor trauma and affects surgical outcome of laminoplasty.

PMID- 29017107
TI  - Vitamin D and parathyroid hormone are associated with gait instability and poor
      balance performance in mid-age to older aged women.
AB  - CONTEXT: Vitamin D status and parathyroid hormone (PTH) levels influence the risk
      of accidental falls in older people, but the mechanisms underlying this effect
      remain unclear. OBJECTIVE: Investigate the relationship between circulating PTH
      and 25 hydroxyvitamin D (25-OHD) levels and clinical tests of gait stability and
      balance as physical fall risk factors. We hypothesized that high levels of PTH
      and low 25-OHD levels would be significantly associated with gait stability and
      decreased balance performance. DESIGN: Observational cohort study. SETTING:
      Australian community. PARTICIPANTS: 119 healthy, ambulatory female twin adults
      aged 47-80 years residing in Victoria, Australia. OUTCOME MEASURES: Serum PTH and
      25-OHD levels with clinical tests of gait stability [double support duration
      (DSD)] and dynamic balance (Step Test). Associations were investigated by
      regression analysis and by comparing groups divided by tertiles of PTH (<3.5, 3.5
      4.9, >4.9pmol/L) and 25-OHD (<53, 53-75, >75 nmol/L) using analysis of variance.
      RESULTS: Serum PTH was associated positively with DSD, with an increase of 10.6
      15.7% when the mid and highest PTH tertiles were compared to the lowest tertile
      (p <0.025) when 25-OHD was included in the regression analysis. 25-OHD was
      significantly associated with DSD (greater by 10.6-11.1% when lowest and mid
      tertiles compared with the highest 25-OHD tertile) (p <0.025) and dynamic balance
      (better performance by 12.6% in the highest compared with the lowest 25OHD
      tertile) (p <0.025). CONCLUSION: These findings reveal an important new
      relationship between parathyroid hormone and gait stability parameters and add to
      understanding of the role of 25-OHD in motor control of gait and dynamic balance
      in community-dwelling women across a wide age span.

PMID- 29017108
TI  - Sexual orientation disparities in prescription drug misuse among a nationally
      representative sample of adolescents: Prevalence and correlates.
AB  - OBJECTIVE: Sexual minority adolescents (SMA) may be at disproportionate risk for
      misusing prescription psychotropic medications compared to their heterosexual
      peers. However, generalizable studies specific to this age group are lacking. The
      current study aimed to describe the prevalence of sexual orientation disparities
      in prescription drug misuse among a nationally representative sample of
      adolescents as well as to examine key correlates of misuse. METHOD: Using data
      from the National Youth Risk Behavior Survey, we conducted stepwise multivariable
      weighted logistic regressions, sequentially controlling for demographics,
      experiences of victimization, mental health, and other illicit substance use.
      RESULTS: Adjusting for grade and race/ethnicity, female SMA and gay and unsure
      males had significantly elevated odds of ever misusing a prescription drug
      compared to heterosexual adolescents (ORs from 1.7-2.5). Most sexual orientation
      disparities among females remained significant with the addition of victimization
      and mental health covariates but attenuated completely after controlling for
      other illicit drug use. The effect for unsure males attenuated when victimization
      variables were included, but the effect for gay males remained significant
      through the final model. Controlling for other illicit drug use, mental health
      variables remained significant correlates for females whereas only forced sex was
      significant for males. CONCLUSION: These results suggest experiences of
      victimization and mental health partially account for the disparities in
      prescription drug misuse between SMA and heterosexual adolescents, and their
      effects may differ by sex. A combination of structural, individual coping, and
      universal drug prevention approaches should be used to make the largest impact on
      reducing these disparities.

PMID- 29017109
TI  - Development of a LC-MS/MS method to investigate the interference of
      pharmacokinetics of the main constituents in Saxifraga stolonifera: Involvement
      of drug metabolism enzymes.
AB  - A specific and sensitive LC-MS/MS method was established for the simultaneous
      determination of bergenin, protocatechuic acid and gallic acid, the main active
      constituents of Saxifraga stolonifera (L.) Meerb. herb, in rat plasma. After
      fully validated, the method was applied to the comparative pharmacokinetic
      studies of the three compounds orally administered alone and in combination in
      the S. stolonifera extract, respectively. The results showed that the
      pharmacokinetic parameters, including Cmax, Tmax, AUC, CLz/F, MRT0-infinity, were
      significantly different for both bergenin and protocatechuic acid in the extract
      as compared to the corresponding compounds administered alone. However, the
      pharmacokinetic behavior of gallic acid in the extract did not differ from that
      administered alone. Further studies found that quercetin, coexisting in the herb
      extract, significantly decreased the glucuronidation of bergenin through
      inhibiting the activities of UGT1A1 and UGT1A3, and reduced the metabolism of
      protocatechuic acid by inhibiting the activity of catechol-O-methyltransferase.
      Quercetin and other flavonoids occurring in the S. stolonifera extract might
      increase the absorption and improve the bioavailability of bergenin and
      protocatechuic acid by slowing down the liver metabolism. The findings provide a
      good guidance for the development and clinical application of S. stolonifera.

PMID- 29017111
TI  - Origin and spatial distribution of metals in moss samples in Albania: A hotspot
      of heavy metal contamination in Europe.
AB  - This study presents the spatial distribution of 37 elements in 48 moss samples
      collected over the whole territory of Albania and provides information on sources
      and factors controlling the concentrations of elements in the moss. High
      variations of trace metals indicate that the concentrations of elements are
      affected by different factors. Relations between the elements in moss,
      geochemical interpretation of the data, and secondary effects such as redox
      conditions generated from local soil and/or long distance atmospheric transport
      of the pollutants are discussed. Zr normalized data, and the ratios of different
      elements are calculated to assess the origin of elements present in the current
      moss samples with respect to different geogenic and anthropogenic inputs. Factor
      analysis (FA) is used to identify the most probable sources of the elements. Four
      dominant factors are identified, i.e. natural contamination; dust emission from
      local mining operations; atmospheric transport of contaminants from local and
      long distance sources; and contributions from air borne marine salts. Mineral
      particle dust from local emission sources is classified as the most important
      factor affecting the atmospheric deposition of elements accumulated in the
      current moss samples. The open slag dumps of mining operation in Albania is
      probably the main factor contributing to high contents of Cr, Ni, Fe, Ti and Al
      in the moss. Enrichment factors (EF) were calculated to clarify whether the
      elements in the present moss samples mainly originate from atmospheric deposition
      and/or local substrate materials.

PMID- 29017110
TI  - Structural characterization of dimethyldithiodenafil and
      dimethylthiocarbodenafil, analogs of sildenafil.
AB  - Two analogs of sildenafil (compounds 1 and 2) were detected in three powder
      products acquired from online drug markets during an LC-UV-MS analysis of
      psychotropic drugs. Their structures were established by high-resolution mass
      spectrometry and NMR spectroscopy. Compound 1 was identified as 5-(5-(3,5
      dimethylpiperazine-1-carbonothioyl)-2-ethoxyphenyl)-1-methyl-3-propyl-1H
      pyrazolo[4,3-d]pyrimidine-7(6H)-thione and named dimethyldithiodenafil. Compound
      2 was identified as 5-(5-(3,5-dimethylpiperazine-1-carbonothioyl)-2-ethoxyphenyl)
      1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one and named
      dimethylthiocarbodenafil. Compound 1 was subjected to the phosphodiesterase assay
      (IC50=0.20nM). The three powder products were found to contain 12-19mg of
      dimethyldithiodenafil and 1.4-3.9mg of dimethylthiocarbodenafil per tube.

PMID- 29017112
TI  - Bioaccumulation, distribution and elimination of lindane in Eisenia foetida: The
      aging effect.
AB  - Soil aging will influence the chemical speciation of pesticides, thus affecting
      the uptake route to be bioavailable to the organism. So far, studies on the
      possible effects of the uptake route on the distribution and elimination of
      pesticides in the organism that also considers effects of aging are limited. In
      our study, Eisenia fetida was exposed to 4.5 mg kg-1 lindane aging for 0, 30 and
      180 d, and the accumulation, distribution and elimination of lindane in the
      earthworms were analyzed. The results showed that the 6 h Tenax-extracted
      fraction exhibited a good linear correlation with the lindane accumulated in the
      earthworms. With aging time increasing, the bioaccumulation of lindane decreased
      and the accumulative balance was more easily reached in the earthworms. Lindane
      distributions were found in the whole earthworm and the proportions of lindane
      content at sub-organism level and the mass distribution of each fraction were
      similar for 0 d and 180 d aged groups. The foregut accumulated the highest
      content of lindane (20%) relative to its low mass distribution proportion (10%).
      The elimination rate of lindane in the earthworms decreased with aging time
      extending. Our conclusion was that the 6 h Tenax extraction could be used to
      assess the bioavailability of aging lindane. Although soil aging decreased the
      bioavailability of lindane, the soil-bound lindane entered the earthworm through
      dietary route would take longer to depurate from the organisms than free lindane,
      which implied the potential ecological risk of bound pesticide residues.

PMID- 29017113
TI  - Fate of bisphenol A, perfluorooctanoic acid and perfluorooctanesulfonate in two
      different types of sewage treatment works in Hong Kong.
AB  - This study aimed at investigating the removal efficiencies of perfluorooctanoate
      (PFOA), perfluorooctane sulfonate (PFOS) and bisphenol A (BPA) of two major
      sewage treatment works in Hong Kong: Stonecutters Island STW (SCISTW) which
      adopts chemically enhanced primary treatment (CEPT) process and Sha Tin STW
      (STSTW) which employs biological treatment. Liquid portion (LP) and particulate
      matter (PM) of liquid sewage samples and sludge samples were collected and
      followed by liquid chromatograph system. It was found that BPA (44.6 +/- 35.1%)
      generally achieved higher TRE than the two other chemicals (PFOS (-18.8 +/-
      34.8%) and PFOA (-104 +/- 86.8%)) in STSTW (p < 0.05). Most of the PFOA, PFOS and
      BPA was discharged through final effluent (PFOA: 95.6 +/- 1.00% and 94.5 +/-
      3.13%; PFOS: 77.7 +/- 1.48% and 72.6 +/- 6.07%; BPA: 99.2 +/- 0.950% and 92.8 +/-
      7.25%, respectively) rather than stored in the sludge/cake (PFOA: 4.45 +/- 1.00%
      and 5.47 +/- 3.13%, PFOS: 22.3 +/- 1.48% and 27.4 +/- 6.07%, BPA: 0.844 +/-
      0.950% and 7.20 +/- 7.25%, respectively). After the sewage purification process,
      the two STW released considerable amounts of PFOA, PFOS and BPA in the final
      effluent (PFOA: 0.638 +/- 0.227 kg/year; PFOS: 0.409 +/- 0.126 kg/year; BPA: 10.4
      +/- 3.83 kg/year in STSTW; PFOA: 3.08 +/- 1.415 kg/year; PFOS: 2.13 +/- 0.452
      kg/year; BPA: 714 +/- 768 kg/year in SCISTW) and in the sludge (PFOA: 0.0360 +/-
      0.0250 kg/year; PFOS: 0.149 +/- 0.00100 kg/year; BPA: 1.09 +/- 1.47 kg/year in
      STSTW; PFOA: 0.139 +/- 0.0670 kg/year; PFOS: 0.606 +/- 0.0780 kg/year; BPA: 3.05
      +/- 3.95 kg/year in SCISTW). This study may help to provide crucial information
      for further development of municipal sewage system in treating synthetic emerging
      chemicals.

PMID- 29017114
TI  - Association between the IRF6 rs2235371 polymorphism and the risk of nonsyndromic
      cleft lip with or without cleft palate in Chinese Han populations: A meta
      analysis.
AB  - OBJECTIVE: To investigate the association between the risk of nonsyndromic cleft
      lip with or without cleft palate (NSCL/P) and the IRF6 rs2235371 (C>T)
      polymorphism in Chinese Han populations. DESIGN: PubMed, Web of Science and
      EMBASE were searched through May 31, 2016, to select eligible studies. Pooled
      odds ratios (ORs) with 95% confidence intervals (95% CIs) were applied to
      estimate the risk of NSCL/P associated with the IRF6 rs2235371 polymorphism.
      Subgroup analyses were conducted according to NSCL/P types (CLO, CPO and CLP) and
      the geographical location (Northern China and Southern China). Publication bias
      and sensitivity analyses were performed to assess the reliability of the results.
      RESULTS: A total of 1275 NSCL/P cases and 1294 controls from seven eligible case
      control studies were included. In the overall analysis, a significant association
      between the IRF6 rs2235371 polymorphism and the risk of NSCL/P was identified
      under all genetic models, with the exception of the recessive model (T vs. C:
      OR=0.68, 95%CI=0.60-0.76, P<0.00001). A subgroup analysis by NSCL/P types
      indicated that the variant T allele significantly decreased the risk of CLO and
      CLP but not CPO. A subgroup analysis of the geographical location further showed
      significantly decreased susceptibility in Northern China under all genetic
      models, but in Southern China, only the heterozygote and dominant models showed a
      significantly decreased risk of NSCL/P. Funnel plot analysis and the Egger linear
      regression method detected no publication bias. CONCLUSIONS: The IRF6 rs2235371 T
      allele decreased the risk of NSCL/P in Chinese Han populations. However, further
      studies with large sample sizes should be conducted to confirm this association.

PMID- 29017116
TI  - Improved proteolytic stability and potent activity against Leishmania infantum
      trypanothione reductase of alpha/beta-peptide foldamers conjugated to cell
      penetrating peptides.
AB  - The objective of the current study was to enhance the proteolytic stability of
      peptide-based inhibitors that target critical protein-protein interactions at the
      dimerization interface of Leishmania infantum trypanothione reductase (Li-TryR)
      using a backbone modification strategy. To achieve this goal we carried out the
      synthesis, proteolytic stability studies and biological evaluation of a small
      library of alpha/beta3-peptide foldamers of different length (from 9-mers to 13
      mers) and different alpha->beta substitution patterns related to prototype linear
      alpha-peptides. We show that several 13-residue alpha/beta3-peptide foldamers
      retain inhibitory potency against the enzyme (in both activity and dimerization
      assays) while they are far less susceptible to proteolytic degradation than an
      analogous alpha-peptide. The strong dependence of the binding affinities for Li
      TryR on the length of the alpha,beta-peptides is supported by theoretical
      calculations on conformational ensembles of the resulting complexes. The
      conjugation of the most proteolytically stable alpha/beta-peptide with
      oligoarginines results in a molecule with potent activity against L. infantum
      promastigotes and amastigotes.

PMID- 29017117
TI  - Characterisation of hyaluronic acid methylcellulose hydrogels for 3D bioprinting.
AB  - Hydrogels containing hyaluronic acid (HA) and methylcellulose (MC) have shown
      promising results for three dimensional (3D) bioprinting applications. However,
      several parameters influence the applicability bioprinting and there is scarce
      data in the literature characterising HAMC. We assessed eight concentrations of
      HAMC for printability, swelling and stability over time, rheological and
      structural behaviour, and viability of mesenchymal stem cells. We show that HAMC
      blends behave as viscous solutions at 4 degrees C and have faster gelation times
      at higher temperatures, typically gelling upon reaching 37 degrees C. We found
      the storage, loss and compressive moduli to be dependent on HAMC concentration
      and incubation time at 37 degrees C, and show the compressive modulus to be
      strain-rate dependent. Swelling and stability was influenced by time, more so
      than pH environment. We demonstrated that mesenchymal stem cell viability was
      above 75% in bioprinted structures and cells remain viable for at least one week
      after 3D bioprinting. The mechanical properties of HAMC are highly tuneable and
      we show that higher concentrations of HAMC are particularly suited to cell
      encapsulated 3D bioprinting applications that require scaffold structure and
      delivery of cells.

PMID- 29017118
TI  - Effects of sludge thermal-alkaline pretreatment on cationic red X-GRL adsorption
      onto pyrolysis biochar of sewage sludge.
AB  - Thermal-alkaline pretreatment has traditionally been used to enhance anaerobic
      sludge digestion. In this study, after removing the supernatant, which could be
      used in anaerobic digestion, the Residual Solids of Thermal-Alkaline pretreated
      sewage Sludge (RSTAS) were used to prepare biochar via pyrolysis, which could
      then adsorb Cationic Red X-GRL(X-GRL). The experimental results showed that the
      RSTAS-biochar had a higher BET surface area and total pore volume than the
      biochar prepared from raw sludge (RS) (43.5% and 33.3%, respectively). The
      pretreatment enhanced the X-GRL adsorption capacity of the biochar by 1.5-49.2%
      at dosages between 12.5-100.0g/g, and the highest adsorption capacity increased
      from 39.1mg/g to 47.6mg/g. The biochar from RSTAS had a wider application pH
      range for X-GRL adsorption. The kinetics and isotherms for X-GRL adsorption onto
      the two biochars were well fitted to the pseudo-second-order and Langmuir
      isotherm models, respectively, which suggested that thermal-alkaline pretreatment
      had little effect on the adsorption mechanisms of X-GRL onto biochar.

PMID- 29017119
TI  - Mn2+ promoted Cr(VI) reduction with oxalic acid: The indispensable role of In
      situ generated Mn3.
AB  - In this study, we demonstrate that Mn2+ can greatly promote the Cr(VI) reduction
      by oxalic acid at pH<5 via an induction period and a subsequent auto-acceleration
      process. The Cr(VI) reduction rate constant during the late auto-acceleration
      process was about 10 times that of the initial induction period. Characterization
      results revealed that this interesting two-step Cr(VI) reduction phenomenon was
      attributed to the in-situ generated Mn3+ by the oxidation of Mn2+ with Cr(VI) in
      the presence of oxalic acid during the induction period. The in-situ generated
      Mn3+ might complex with oxalate and Cr(VI) to produce a ternary complex, thus
      facilitating the electron transfer from oxalate to Cr(VI) to automatically
      accelerate the Cr(VI) reduction process. These findings shed insight into the
      possible roles of widely existed Mn ions (Mn2+ and Mn3+) and oxalic acid in the
      transformation of Cr(VI) in natural aquatic environment, and also provided an
      efficient way to remediate Cr(VI)-containing acid wastewater.

PMID- 29017115
TI  - A review of the basics of mitochondrial bioenergetics, metabolism, and related
      signaling pathways in cancer cells: Therapeutic targeting of tumor mitochondria
      with lipophilic cationic compounds.
AB  - The present review is a sequel to the previous review on cancer metabolism
      published in this journal. This review focuses on the selective antiproliferative
      and cytotoxic effects of mitochondria-targeted therapeutics (MTTs) in cancer
      cells. Emerging research reveals a key role of mitochondrial respiration on tumor
      proliferation. Previously, a mitochondria-targeted nitroxide was shown to
      selectively inhibit colon cancer cell proliferation at submicromolar levels. This
      review is centered on the therapeutic use of MTTs and their bioenergetic
      profiling in cancer cells. Triphenylphosphonium cation conjugated to a parent
      molecule (e.g., vitamin-E or chromanol, ubiquinone, and metformin) via a linker
      alkyl chain is considered an MTT. MTTs selectively and potently inhibit
      proliferation of cancer cells and, in some cases, induce cytotoxicity. MTTs
      inhibit mitochondrial complex I activity and induce mitochondrial stress in
      cancer cells through generation of reactive oxygen species. MTTs in combination
      with glycolytic inhibitors synergistically inhibit tumor cell proliferation. This
      review discusses how signaling molecules traditionally linked to tumor cell
      proliferation affect tumor metabolism and bioenergetics (glycolysis, TCA cycle,
      and glutaminolysis).

PMID- 29017120
TI  - The flame retardancy and smoke suppression effect of a hybrid containing CuMoO4
      modified reduced graphene oxide/layered double hydroxide on epoxy resin.
AB  - The co-precipitation method was used to synthesize a hybrid with MgAl-layered
      double hydroxide loaded graphene (RGO-LDH). CuMoO4 was then introduced onto the
      surface of RGO-LDH to prepare a hybrid with CuMoO4 modified RGO-LDH (RGO
      LDH/CuMoO4). The composition, structure and morphology of RGO-LDH/CuMoO4 were
      characterized by X-ray diffraction, Laser raman spectroscopy and Transmission
      electron microscope-energy-dispersive X-ray spectroscopy. It was found that the
      hybrid of RGO-LDH/CuMoO4 had been successfully prepared. The effects of flame
      retardancy and smoke suppression of epoxy resin were studied with added RGO
      LDH/CuMoO4. Results showed that the PHRR and THR of the EP composite with RGO
      LDH/CuMoO4 added were decreased dramatically. The char yield, LOI and UL-94
      vertical burning rating of the EP composite were increased, with improved flame
      ratardancy. In addition, the SPR, TSP, and Ds,max of the EP composite were
      decreased drastically with added RGO-LDH/CuMoO4. Its improved flame retardancy
      and smoke suppression performance were due mainly to the physical barrier of
      graphene and LDH, and the catalytic carbonization function of LDH. Meanwhile,
      Cu2O and MoO3 generated from RGO-LDH/CuMoO4 in the combustion process helped
      enhance the production of char residue and raised the compactness of the char
      layer.

PMID- 29017121
TI  - Efficient degradation of tetrabromobisphenol A via electrochemical sequential
      reduction-oxidation: Degradation efficiency, intermediates, and pathway.
AB  - Tetrabromobisphenol A (TBBPA), a toxic persistent pollutant, should be
      effectively removed from the environment. In this study, an electrochemical
      sequential reduction-oxidation system was proposed by controlling reaction
      atmosphere with Pd-Fe nanoparticles modified Ni foam (Pd-Fe/Ni) electrode as
      cathode for TBBPA degradation. To obtain an efficient Pd-Fe/Ni electrode for
      TBBPA degradation, various factors, like Pd loading, Fe2+ adding amounts, were
      examined. The Pd-Fe/Ni electrode exhibited higher TBBPA conversion and
      debromination than the counterparts, due to the synergism of Fe0 and
      electrochemical reduction. Similar TBBPA conversions and debromination ratios
      were observed for the cases of sparging N2 only and sparging N2 followed by air,
      which were higher than those of aeration. Reductive debromination occurred while
      first bubbling N2, forming tri-BBPA, di-BBPA, mono-BBPA and BPA; and these
      intermediates were likely to be further oxidized by OH generated from H2O2
      together with Pd-Fe/Ni electrode under aeration. Reductive and oxidative
      intermediates (including aromatic ring-opened product) were identified by HPLC
      and UPLC-QTOF-MS. Based on the intermediates, the possible TBBPA degradation
      mechanism and pathway were proposed. This study demonstrates that sequential
      reduction-oxidation process tuned by N2 and air bubbling was favored for TBBPA
      degradation, thus, it should be a promising process for HOCs degradation.

PMID- 29017122
TI  - Biochemical responses of Solea senegalensis after continuous flow exposure to
      urban effluents.
AB  - Urban effluent potential toxicity was assessed by a battery of biomarkers aimed
      at determining sub-lethal effects after continuous exposure on the marine
      organism Solea senegalensis. Specimens were exposed to five effluent
      concentrations (1/2, 1/4, 1/8, 1/16, 1/32) during 7-days, simulating the
      dispersion plume at the discharge point. Three different groups of biomarkers
      were selected in the present study: biomarkers of exposure (Phase I: EROD and
      DBF; Phase II: GST), biomarkers with antioxidant responses (GR and GPX) and
      biomarkers of effects (DNA damage and LPO). Additionally, a biological depuration
      treatment (photobiotreatment (PhtBio)) was tested in order to reduce the adverse
      effects on aquatic organisms. Effluent exposure caused sub-lethal responses in
      juvenile fish suggesting oxidative stress. After PhtBio application,
      concentrations of the major part of measured contaminants were reduced, as well
      as their bioavailability and adverse effects.

PMID- 29017123
TI  - Organic contamination and remediation in the agricultural soils of China: A
      critical review.
AB  - Soil pollution is a global problem in both developed and developing countries.
      Countries with rapidly developing economies such as China are faced with
      significant soil pollution problems due to accelerated industrialization and
      urbanization over the last decades. This paper provides an overview of published
      scientific data on soil pollution across China with particular focus on organic
      contamination in agricultural soils. Based on the related peer-reviewed papers
      published since 2000 (n=203), we evaluated the priority organic contaminants
      across China, revealed their spatial and temporal distributions at the national
      scale, identified their possible sources and fates in soil, assessed their
      potential environmental risks, and presented the challenges in current
      remediation technologies regarding the combined organic pollution of agricultural
      soils. The primary pollutants in Northeast China were polycyclic aromatic
      hydrocarbons (PAHs) due to intensive fossil fuel combustion. The concentrations
      of organochlorine pesticides (OCPs) and phthalic acid esters (PAEs) were higher
      in North and Central China owing to concentrated agricultural activities. The
      levels of polychlorinated biphenyls (PCBs) were higher in East and South China
      primarily because of past industrial operations and improper electronic waste
      processing. The co-existence of organic contaminants was severe in the Yangtze
      River Delta, Pearl River Delta, and Beijing-Tianjin-Hebei Region, which are the
      most populated and industrialized regions in China. Integrated biological
      chemical remediation technologies, such as surfactant-enhanced bioremediation,
      have potential uses in the remediation of soil contaminated by multiple
      contaminants. This critical review highlighted several future research directions
      including combined pollution, interfacial interactions, food safety,
      bioavailability, ecological effects, and integrated remediation methods for
      combined organic pollution in soil.

PMID- 29017124
TI  - Shifts of radiocesium vertical profiles in sediments and their modelling in
      Japanese lakes.
AB  - Vertical profiles of radiocesium concentrations were measured in sediment cores
      collected at various times after the 2011 Fukushima nuclear accident in five
      Japanese lakes (Hinuma, Kasumigaura, Kitaura, Onogawa and Sohara) with different
      morphological and trophic characteristics in order to investigate the
      sedimentation-diffusion processes. In lakes where sediments had high porosities
      and experienced considerable wave action due to shallowness, we observed rapid
      penetration of radiocesium to a certain depth just after the accident, followed
      by downward movement of the peak depths. In contrast, gradual downward transfers
      of distinct peaks were found in other types of lakes. A one-dimensional
      differential sediment model with water-sediments interaction processes was
      constructed to describe the vertical shift of radiocesium profiles. Our proposed
      submodels relating to the length scales of the mixing using wind-induced stress
      and porosity of sediments were constructed based on one measurement of the
      vertical distribution of radiocesium in three lakes (Hinuma, Kasumigaura and
      Sohara). This model was then validated using samples from those lakes in
      different years, as well as from two other lakes. Good agreement was obtained. We
      discuss our findings, the limits of model application, and future research
      targets.

PMID- 29017125
TI  - Thaw depth spatial and temporal variability at the Limnopolar Lake CALM-S site,
      Byers Peninsula, Livingston Island, Antarctica.
AB  - A new Circumpolar Active Layer Monitoring (CALM) site was established in 2009 at
      the Limnopolar Lake watershed in Byers Peninsula, Livingston Island, Antarctica,
      to provide a node in the western Antarctic Peninsula, one of the regions that
      recorded the highest air temperature increase in the planet during the last
      decades. The first detailed analysis of the temporal and spatial evolution of the
      thaw depth at the Limnopolar Lake CALM-S site is presented here, after eight
      years of monitoring. The average values range between 48 and 29cm, decreasing at
      a ratio of 16cm/decade. The annual thaw depth observations in the 100*100 m CALM
      grid are variable (Variability Index of 34 to 51%), although both the Variance
      Coefficient and the Climate Matrix Analysis Residual point to the internal
      consistency of the data. Those differences could be explained then by the terrain
      complexity and node-specific variability due to the ground properties. The
      interannual variability was about 60% during 2009-2012, increasing to 124% due to
      the presence of snow in 2013, 2015 and 2016. The snow has been proposed here as
      one of the most important factors controlling the spatial variability of ground
      thaw depth, since its values correlate with the snow thickness but also with the
      ground surface temperature and unconfined compression resistance, as measured in
      2010. The topography explains the thaw depth spatial distribution pattern, being
      related to snowmelt water and its accumulation in low-elevation areas (downslope
      flow). Patterned grounds and other surface features correlate well with high thaw
      depth patterns as well. The edaphic factor (E=0.05842m2/ degrees C.day; R2=0.63)
      is in agreement with other permafrost environments, since frozen index (F>0.67)
      and MAAT (<-2 degrees C) denote a continuous permafrost existence in the area.
      All these characteristics provided the basis for further comparative analyses
      between others nearby CALM sites.

PMID- 29017126
TI  - Short-term facilitation of microbial litter decomposition by ultraviolet
      radiation.
AB  - Solar radiation plays an important role in carbon cycling by increasing the
      decomposition rates of plant litter and soil organic matter (i.e.
      photodegradation). Previous work suggests that exposure to radiation can
      facilitate microbial decomposition of litter by altering litter chemistry and
      consequently litter degradability (i.e. photopriming). However, it remains
      unclear to what extent photopriming contributes to litter decomposition processes
      and on what timescale photopriming operates. We conducted laboratory experiments
      to compare the effects of UV photopriming at two temporal scales (months versus
      days). In one experiment, we found that four months of UV exposure induced a
      significant but small (3-4%) mass loss in two of three litter species commonly
      found in California oak savanna; however, UV exposure did not alter litter
      degradability as measured by microbial respiration in an incubation experiment.
      We also found that UV exposure had limited effects on lignin and other cell wall
      structures, but one month of microbial decomposition (in absence of UV exposure)
      significantly reduced lignin beta-aryl ether inter-unit linkages and acetylated
      xylans. These results indicate that abiotic photodegradation alone was
      ineffective at breaking down lignin. In another experiment, litter of a common
      grass was exposed to either alternating UV radiation and dark conditions or
      constant darkness for 128days. We found that the alternating UV exposure
      increased litter CO2 production in both dark and UV phases over that observed in
      constant darkness. This led to a 35% greater release of CO2 from the alternating
      UV exposure treatment between days 65 and 128 of the experiment. These results
      demonstrate that alternating UV exposure with dark conditions is key to enabling
      photopriming on a timescale of days. Overall, we identify short-term photopriming
      as a novel mechanism behind photodegradation. Our results also challenge the
      conventional hypothesis that abiotic processes are primarily responsible for
      degrading lignin during photodegradation.

PMID- 29017128
TI  - Potential for using remote sensing to estimate carbon fluxes across northern
      peatlands - A review.
AB  - Peatlands store large amounts of terrestrial carbon and any changes to their
      carbon balance could cause large changes in the greenhouse gas (GHG) balance of
      the Earth's atmosphere. There is still much uncertainty about how the GHG
      dynamics of peatlands are affected by climate and land use change. Current field
      based methods of estimating annual carbon exchange between peatlands and the
      atmosphere include flux chambers and eddy covariance towers. However, remote
      sensing has several advantages over these traditional approaches in terms of
      cost, spatial coverage and accessibility to remote locations. In this paper, we
      outline the basic principles of using remote sensing to estimate ecosystem carbon
      fluxes and explain the range of satellite data available for such estimations,
      considering the indices and models developed to make use of the data. Past
      studies, which have used remote sensing data in comparison with ground-based
      calculations of carbon fluxes over Northern peatland landscapes, are discussed,
      as well as the challenges of working with remote sensing on peatlands. Finally,
      we suggest areas in need of future work on this topic. We conclude that the
      application of remote sensing to models of carbon fluxes is a viable research
      method over Northern peatlands but further work is needed to develop more
      comprehensive carbon cycle models and to improve the long-term reliability of
      models, particularly on peatland sites undergoing restoration.

PMID- 29017127
TI  - Identification of platinum nanoparticles in road dust leachate by single particle
      inductively coupled plasma-mass spectrometry.
AB  - Elevated platinum (Pt) concentrations are found in road dust as a result of
      emissions from catalytic converters in vehicles. This study investigates the
      occurrence of Pt in road dust collected in Ghent (Belgium) and Gothenburg
      (Sweden). Total Pt contents, determined by tandem ICP-mass spectrometry (ICP
      MS/MS), were in the range of 5 to 79ngg-1, comparable to the Pt content in road
      dust of other medium-sized cities. Further sample characterization was performed
      by single particle (sp) ICP-MS following an ultrasonic extraction procedure using
      stormwater runoff for leaching. The method was found to be suitable for the
      characterization of Pt nanoparticles in road dust leachates. The extraction was
      optimized using road dust reference material BCR-723, for which an extraction
      efficiency of 2.7% was obtained by applying 144kJ of ultrasonic energy. Using
      this method, between 0.2% and 18% of the Pt present was extracted from road dust
      samples. spICP-MS analysis revealed that Pt in the leachate is entirely present
      as nanoparticles of sizes between 9 and 21nm. Although representing only a minor
      fraction of the total content in road dust, the nanoparticulate Pt leachate is
      most susceptible to biological uptake and hence most relevant in terms of
      bioavailability.

PMID- 29017129
TI  - Mapping relative humidity, average and extreme temperature in hot summer over
      China.
AB  - Air temperature and relative humidity are the key variables in environmental
      health research. Both of them are difficult to map especially at national scale
      because of spatial heterogeneity. This paper presents a methodology for mapping
      relative humidity, average and extreme temperature in hot summer (June to August)
      over China. Several data as explanatory variables were applied to random forest
      regression models to predict relative humidity and temperatures, including
      surface reflectance, land cover, digital elevation model (DEM), enhanced
      vegetation index (EVI), latitude, nighttime lights (NLs), as well as buffer zones
      of road, railroad, river system and administration center. Results based on cross
      validation reflect acceptable prediction errors in estimating relative humidity
      (RMSE=7.4%), average temperature (RMSE=2.4 degrees C), average maximum
      temperature (RMSE=2.5 degrees C), and extreme maximum temperature (RMSE=2.6
      degrees C). Despite the strong correlation between average and extreme
      temperatures, significant differences exist in their spatial distribution along
      the latitude direction, especially in the areas such as Hebei, Szechwan, Hubei,
      Henan, Shandong, and Inner Mongolia. Specifically, social economic activity,
      relative humidity and vegetation tend to affect extreme heat events, and both
      latitude and DEM (i.e., geographical position) determine the average level of
      temperature. Compared with interpolation technology and statistical methods, the
      proposed methodology demonstrates the ability to generate relative humidity and
      temperature maps with finer gradients in hot summer over China.

PMID- 29017130
TI  - The biochemical response of willow plants (Salix viminalis L.) to the use of
      sewage sludge from various sizes of wastewater treatment plant.
AB  - Sewage sludge production is increasing, as is the importance of its safe and
      sustainable disposal. The study examine the impact of fertilizing poor quality
      soil with sewage sludge from three sizes of wastewater treatment plants (WTP)
      (small, medium and large) located in Central Poland, applied in two doses (3 and
      9tons per hectare), on biomass yield and selected biochemical parameters in
      willow plants. The WTPs were selected based on the size criterion given in Polish
      regulations. Three variables were analyzed in the leaves and roots of willow
      cuttings after twenty weeks of cultivation: the degree of oxidative reaction,
      assessed as thiobarbituric-acid-reactive substances (TBARS) content; catalase
      activity (CAT, EC 1.11.1.6), reflecting the efficiency of the antioxidative
      response; and changes in the concentration of proline, one of the major cellular
      osmoprotectants. For plants growing in poor-quality soil, sewage sludge
      administration results in a large increase of willow biomass by creating good
      conditions for plant growth associated with protection against oxidative damage,
      efficient functioning of the antioxidant system and maintenance of the osmotic
      balance between the soil environment and plant roots. The greatest increase was
      204% of control in the case of 9tha-1 sludge from the medium WTP. Biomass
      production correlated with the applied sludge dose. After sewage sludge
      application lipid peroxides were reduced in leaves (81%) and roots (69%), CAT
      activity was enhanced (to 855% in leaves) and proline level was increased in root
      tissues. The application of sewage sludge originating from small WTPs offers the
      best conditions than larger WTPs: sludge from large WTPs may cause oxidative
      damage and exceed the possibilities of plants to counteract stress factors,
      especially when used in high doses.

PMID- 29017131
TI  - Abiotic and biotic drivers of aboveground biomass in semi-steppe rangelands.
AB  - Rangelands play an important role in the biodiversity conservation and ecosystem
      functions. Yet, few studies have assessed the effects of biotic and abiotic
      factors on aboveground biomass across plant growth forms and at whole-community
      level in rangelands. Here, we hypothesized that aboveground biomass is driven by
      both biotic (plant coverage, species richness and evenness) and abiotic factors
      (soil textural properties and topographic factors) but biotic factors may best
      predict aboveground biomass, probably due to small spatial scale. To test this
      hypothesis, we performed multiple linear mixed model by including abiotic and
      biotic factors as fixed effects while sites aspects and plant community types
      across sites, and disturbance intensities as random effects, using data from 735
      quadrats across 35 sites in semi-steppe rangelands in Iran. The optimal model for
      shrubs showed that aboveground biomass was positively related to plant coverage,
      species richness, elevation, sand, silt and clay. Aboveground biomass of forbs
      and grasses was positively related to plant coverage, species richness, elevation
      and slope. Whole-community aboveground biomass was positively related to plant
      coverage, species richness and elevation, but negatively to species evenness and
      slope. We conclude that higher aboveground biomass is related to high species
      richness and plant coverage, and located on high elevation and/or slope across
      plant growth forms while having medium-coarse-textured to fine-textured soils for
      adaptation of shrubs only. Few dominant species or niche overlap in whole
      community may also drive high aboveground biomass, and located on high elevation
      with gentle slope. Therefore, we found support for both the niche complementarity
      and selection effects across plant growth forms and at whole-community. In
      addition, this study shows that plant coverage is the best proxy for aboveground
      biomass in the studied rangelands.

PMID- 29017133
TI  - Estimation of soil salt content (SSC) in the Ebinur Lake Wetland National Nature
      Reserve (ELWNNR), Northwest China, based on a Bootstrap-BP neural network model
      and optimal spectral indices.
AB  - Soil salinity is recognized worldwide as a major threat to agriculture,
      particularly in arid regions. Producers and decision-makers thus require updated
      and accurate maps of salinity in agronomical and environmentally relevant
      regions. The goals of this study were to test various regression models for
      estimating soil salt content based on hyperspectral data, HJ-CCD images, and
      Landsat OLI data using; develop optimal band Difference Index (DI), Ratio Index
      (RI), and Normalization Index (NDI) algorithms for monitoring soil salt content
      using image and spectral data; and to compare the performances of the proposed
      models using a Bootstrap-BP neural network model (Bootstrap-BPNN) from different
      data sources. The results showed that previously published optimal remote sensing
      parameters can be applied to estimate the soil salt content in the Ebinur Lake
      Wetland National Nature Reserve (ELWNNR). Optimal band combination indices based
      on DI, RI, and NDI were developed for different data sources. Then, the Bootstrap
      BP neural network model was built using 1000 groups of Bootstrap samples of
      remote sensing indices (DI, RI and NDI) and soil salt content. When verifying the
      accuracy of hyperspectral data, the model yields an R2 value of 0.95, a root mean
      square error (RMSE) of 4.38g/kg, and a residual predictive deviation (RPD) of
      3.36. The optimal model for remote sensing images was the first derivative model
      of Landsat OLI, which yielded R2 value of 0.91, RMSE of 4.82g/kg, and RPD of
      3.32; these data indicated that this model has a high predictive ability. When
      comparing the salinization monitoring accuracy of satellite images to that of
      ground hyperspectral data, the accuracy of the first derivative of the Landsat
      OLI model was close to that of the hyperspectral parameter model. Soil salt
      content was inverted using the first derivative of the Landsat OLI model in the
      study area.

PMID- 29017132
TI  - A duodecennial national synthesis of antibiotics in China's major rivers and seas
      (2005-2016).
AB  - The occurrence of 94 antibiotics in water and sediments from seven major rivers
      and four seas in China during 2005-2016 was reviewed. Twelve antibiotics were
      most frequently detected in both water and sediment samples, including 3
      sulfonamides (SAs), 2 tetracyclines (TCs), 4 fluoroquinolones (FQs), and 3
      macrolides (MLs). Their median concentrations were below 100ng/L and 100ng/g in
      river water and sediments, respectively. The highest median concentrations were
      found in water (1.30-176ng/L) and sediments (0.15-110ng/g) in the Hai River, due
      to its larger population density, higher consumption of antibiotics, and lower
      water flow. The concentrations of TCs and FQs were higher in the Pearl River
      sediments, due to their extensive use in aquaculture. The Yangtze River showed
      lower median concentrations of antibiotics in both water (1.33-17.3ng/L) and
      sediments (0.31-14.8ng/g), resulting from its larger catchment size, and higher
      precipitation and water flow. The Yellow River exhibited lower median
      concentrations of antibiotics in sediments (0.04-9.04ng/g), probably due to low
      organic matter content in sediments and high suspended particle content in water.
      Organic carbon normalized distribution coefficients (Koc) of antibiotics were
      positively correlated with the octanol/water partition coefficients (Kow) of
      antibiotics, and the correlation for MLs with a macrocyclic lactone ring was
      different from that of SAs, FQs, and TCs, likely due to their much larger
      molecular size. Among China's major rivers, the Hai River had the highest
      ecotoxicological risk from antibiotics to algae, invertebrate, fish, and plant.

PMID- 29017134
TI  - Variations in size and composition of colloidal organic matter in a negative
      freshwater estuary.
AB  - Dynamic variations in chemical composition and size distribution of dissolved
      organic matter (DOM) along the river-lake interface in the Fox River plume were
      investigated using ultrafiltration, flow field-flow fractionation, UV-Vis and
      fluorescence spectroscopy and parallel factor analysis. On average, ~67% of bulk
      dissolved organic carbon (DOC) were partitioned in the <1kDa (actual cutoff
      2.5kDa) low molecular weight fraction, and the other 33% were in the 1kDa-0.7MUm
      colloidal phase. Concentrations of DOC and chromophoric DOM in the bulk and size
      fractionated samples decreased monotonously with decreasing conductivity from
      river to bay waters, demonstrating a dominant terrestrial source and quasi
      conservative mixing behavior. However, the percentages of colloidal fluorescent
      DOM increased while those of carbohydrates decreased from river to bay waters,
      showing different mixing behavior in the river plume. Colloidal chromophores and
      humic-like fluorophores were mainly partitioned in the size range of 1-6nm, but a
      bimodal distribution (with peaks at 1-6 and 35-45nm) was observed for colloidal
      protein-like DOM. Along the river-lake transect, the peak locations of
      chromophores, humic-like and small-sized protein-like colloids remained almost
      constant, while the larger-sized protein-like colloids exhibited a slight peak
      shift from 38.3 to 40.4nm, showing a molecular size enhancement from high to low
      conductivity waters, with physical mixing, photochemical/microbial degradation,
      and disaggregation/repartitioning being the important processes affecting the
      variations of DOM size and composition. New results herein should enhance our
      understanding of the heterogeneity of DOM in size and composition and its fate,
      transport and transformation at the river-lake interface and along the aquatic
      continuum as a whole.

PMID- 29017135
TI  - Evaluation of the aqueous phototransformation routes of phenyl ethyl azolic
      fungicides by liquid chromatography accurate mass spectrometry.
AB  - Similarities and differences among the phototransformation routes of four azolic
      fungicides (diniconazole, DIN, imazalil, IMA; penconazole, PEN; and
      propiconazole, PRO) in surface water aliquots are investigated. Selected
      compounds share a common chemical structure consisting on dichlorophenyl and
      azolic rings connected through an ethylene bridge, which is substituted with
      different functionalities. Liquid chromatography quadrupole time-of-flight mass
      spectrometry (LC-QTOF-MS) was employed as analytical technique to follow the time
      course of precursor fungicides and to detect and to identify their photo
      transformation products (TPs). Under solar light, the substituents linked to the
      ethylene chain controlled the stability of the fungicides. Whilst PEN and PRO
      remained stable, DIN and IMA showed moderate reactivities, with half-lives (t1/2)
      of 5.1 and 33.5h, respectively. When exposed to UV (254nm) radiation, all
      compounds were effectively degraded with t1/2 in the range from seconds to a few
      minutes. Dechlorination followed by intramolecular cyclization, between phenyl
      and azolic rings, was identified as a common phototransformation route under UV
      irradiation. Depending on the length and the kind of the functionalities attached
      to the ethylene bridge, additional cyclization reactions are also possible. In
      silico toxicity predictions pointed out to dechlorinated tricyclic TPs as the
      most concerning ones, with predicted lethal concentrations (LC50) in the same
      range as the precursor fungicides.

PMID- 29017136
TI  - Combined spinal epidural in a parturient with tinea versicolor.

PMID- 29017137
TI  - Ovarian vein thrombosis after total laparoscopic hysterectomy with unilateral
      adnexectomy: A case report.
AB  - INTRODUCTION: Ovarian vein thrombosis is a rare but potentially serious
      complication after surgical and gynecologic procedures such as oophorectomy and
      hysterectomy. The association of this event with laparoscopic hysterectomy in
      particular, is very rare. Only two cases have been described so far. PRESENTATION
      OF CASE: We present a case of ovarian vein thrombosis after laparoscopic
      hysterectomy in a 40-year-old with deep endometriosis and multiple intramural
      uterine myomas. Laparoscopic hysterectomy, left oophorectomy, right
      salpingectomy, and suspension (ovariopexy) of the right ovary on the ipsilateral
      round ligament of the uterus were performed, using bipolar electrocautery as a
      hemostatic tool. DISCUSSION: The 7th postoperative day the patient presented to
      our hospital complaining of abdominal pain and fever. An abdominal CT scan
      demonstrated a filling defect and enlargement of the right ovarian vein, a
      finding compatible with ovarian vein thrombosis. She was treated with low
      molecular weight heparin (LMWH). On the 19th postoperative day, an MRI scan was
      performed and did not reveal any pathological findings of the right ovarian vein.
      The patient was discharged on LMWH for three months. Post treatment evaluation
      for thrombophilia was negative for pathological findings. CONCLUSION: Our case is
      a very rare condition. Only two 'similar' cases have been described in the
      literature so far. Bipolar electrocautery and ovariopexy on the ipsilateral round
      ligament during laparoscopic hysterectomy should be evaluated further as possible
      contributing mechanisms for the thrombus formation.

PMID- 29017138
TI  - Pitfalls and errors in measuring jitter.
AB  - The safety factor of neuromuscular transmission can be assessed by measuring the
      neuromuscular jitter, which reflects the time variability of processes in the
      motor end-plate. Jitter is increased in any condition with disturbed end-plate
      function, such as myasthenic conditions and ongoing reinnervation. Jitter is
      increasingly being measured with concentric needle (CN) electrodes, which are
      more prone to artefacts than single fiber EMG recordings. The objective of this
      review is to identify and demonstrate pitfalls that can be seen with CN jitter
      measurements, made with both voluntary activation and electrical stimulation.
      With voluntary activation, errors are caused by poor signal quality;
      inappropriate time reference points on the signal; an irregular firing rate; and
      signals with dual latencies, i.e., "flip-flop." With electrical stimulation,
      additional errors result from insufficient stimulation intensity; from abrupt
      change in firing rate; and from axon reflexes. Many pitfalls cannot be avoided
      during recording and can only be detected during post-processing. It is critical
      to be aware of these artefacts when measuring jitter with CN electrodes.

PMID- 29017139
TI  - Do serum BDNF levels vary in self-harm behavior among adolescents and are they
      correlated with traumatic experiences?
AB  - The aim of this study was to compare serum brain-derived neurotrophic factor
      (BDNF) levels between adolescents that harm themselves, those that receive
      psychiatric treatment but do not harm themselves, healthy adolescents, and
      childhood traumas and to investigate the relationship between traumatic
      experiences and serum BDNF levels. The cases were divided into two groups of 40
      adolescents exhibiting self-harm behavior (self-harm/diagnosed group) and 30
      adolescents receiving psychiatric treatment but not exhibiting self-harm
      behaviors (non self-harm/diagnosed group). The control group (healthy control
      group) consisted of 35 healthy adolescents with no psychiatric disorders or self
      harm behaviors. The adolescents were asked to fill in the Inventory of Statements
      About Self Injury (ISAS) and Childhood Trauma Questionnaire (CTQ). For BDNF
      measurement, blood samples were taken from the cases and controls. The serum BDNF
      level of self-harming adolescents who used the self-cutting method was
      significantly lower than that of other groups, and serum BDNF levels decreased
      with the increase in the emotional neglect and abuse severity of self-harming
      adolescents during childhood. In our study, serum BDNF levels decreased with the
      increase in emotional abuse in self-harming adolescents. This finding may
      indicate that neuroplasticity can be affected by a negative emotional environment
      during the early period.

PMID- 29017140
TI  - Lifelong learning of human actions with deep neural network self-organization.
AB  - Lifelong learning is fundamental in autonomous robotics for the acquisition and
      fine-tuning of knowledge through experience. However, conventional deep neural
      models for action recognition from videos do not account for lifelong learning
      but rather learn a batch of training data with a predefined number of action
      classes and samples. Thus, there is the need to develop learning systems with the
      ability to incrementally process available perceptual cues and to adapt their
      responses over time. We propose a self-organizing neural architecture for
      incrementally learning to classify human actions from video sequences. The
      architecture comprises growing self-organizing networks equipped with recurrent
      neurons for processing time-varying patterns. We use a set of hierarchically
      arranged recurrent networks for the unsupervised learning of action
      representations with increasingly large spatiotemporal receptive fields. Lifelong
      learning is achieved in terms of prediction-driven neural dynamics in which the
      growth and the adaptation of the recurrent networks are driven by their
      capability to reconstruct temporally ordered input sequences. Experimental
      results on a classification task using two action benchmark datasets show that
      our model is competitive with state-of-the-art methods for batch learning also
      when a significant number of sample labels are missing or corrupted during
      training sessions. Additional experiments show the ability of our model to adapt
      to non-stationary input avoiding catastrophic interference.

PMID- 29017141
TI  - Premonitory urges and tics in Tourette syndrome: computational mechanisms and
      neural correlates.
AB  - Tourette syndrome is characterized by open motor behaviors - tics - but another
      crucial aspect of the disorder is the presence of premonitory urges:
      uncomfortable sensations that typically precede tics and are temporarily
      alleviated by tics. We review the evidence implicating the somatosensory cortices
      and the insula in premonitory urges and the motor cortico-basal ganglia-thalamo
      cortical loop in tics. We consider how these regions interact during tic
      execution, suggesting that the insula plays an important role as a nexus linking
      the sensory and emotional character of premonitory urges with their translation
      into tics. We also consider how these regions interact during tic learning,
      integrating the neural evidence with a computational perspective on how
      premonitory-urge alleviation reinforces tics.

PMID- 29017142
TI  - Mechanisms of antidiabetic effects of flavonoid rutin.
AB  - Several lines of evidence suggest that flavonoids that originated from vegetables
      and medicinal plants have beneficial effects on diabetes by improving glycemic
      control, lipid profile, and antioxidant status. Rutin is a flavonoid found in
      many plants and shows a wide range of biological activities including anti
      inflammatory, antioxidant, neuroprotective, nephroprotective, and
      hepatoprotective effects. In this review, the antihyperglycemic property of rutin
      and its protective effects against the development of diabetic complications are
      discussed. Proposed mechanisms for the antihyperglycemic effect of rutin include
      a decrease of carbohydrates absorption from the small intestine, inhibition of
      tissue gluconeogenesis, an increase of tissue glucose uptake, stimulation of
      insulin secretion from beta cells, and protecting Langerhans islet against
      degeneration. Rutin also decreases the formation of sorbitol, reactive oxygen
      species, advanced glycation end-product precursors, and inflammatory cytokines.
      These effects are considered to be responsible for the protective effect of rutin
      against hyperglycemia- and dyslipidemia-induced nephropathy, neuropathy, liver
      damage, and cardiovascular disorders. Taken together, the results of current
      experimental studies support the potential of rutin to prevent or treat
      pathologies associated with diabetes. Well-designed clinical studies are
      suggested to evaluate advantages and limits of rutin for managing diabetes.

PMID- 29017143
TI  - Protective effect of carvacrol on acetic acid-induced colitis.
AB  - The pharmacological therapy for inflammatory bowel diseases continues to be
      problematic, and requires new alternative options. In this study, we tested the
      hypothesis that carvacrol (CAR), a phenolic monoterpene with anti-inflammatory
      and antioxidant activities, can treat experimental colitis in mice. C57BL/6 mice
      (n=8/group) were subjected to intrarectal administration of acetic acid (5%) to
      induce colitis. Mice were pretreated with CAR (25, 50 or 100mg/kg, p.o.) every
      12h for three days prior to the induction. Abdominal hyperalgesia, macroscopic
      and microscopic colon damage, myeloperoxidase (MPO) activity, tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-1beta levels, oxidative stress markers,
      and antioxidant enzyme activities were evaluated. Pretreatment with all doses of
      CAR significantly decreased abdominal hyperalgesia and colon MPO activity and TNF
      alpha and IL-1beta levels. A reduction in macroscopic and microscopic damage
      (p<0.05) was observed at doses of 50 and 100mg/kg CAR. Pretreatment with CAR
      significantly reduced lipid peroxidation (for all doses) and increased sulfhydryl
      groups (at 100mg/kg). This effect was accompanied by a significant increase in
      catalase, superoxide dismutase, and glutathione peroxidase activities. These
      findings indicate that CAR protected mice from acetic acid-induced colitis by
      reducing inflammatory, nociceptive, and oxidative damages.

PMID- 29017145
TI  - Synergetic stimulation of nanostructure and chemistry cues on behaviors of
      fibroblasts and endothelial cells.
AB  - It has been widely accepted that cell behaviors can be affected by multiple kinds
      of biomaterial stimulation signals. Although many literatures have focused on
      studying the multiple biomaterials stimulatory cues in affecting cellular
      behaviors, systematic studies on the effects of individual and combination of
      multiple biomaterials stimulatory cues in regulating cellular behaviors and their
      potential possible mechanisms have rarely been reported. We hypothesized that
      tissue engineering scaffolds with enhanced bioactivity can be designed if
      synergetic effects between different kinds of biomaterial stimulation cues in
      affecting cells behaviors can be found and applied. To prove our concept, in this
      study, electrospun nanofibers were used to provide structure cues and bioactive
      glass (BG) ion extracts were used to provide chemistry cues. The effects of
      single type of electrospun nanofiber structure cues, single type of BG chemical
      cues and combined application of the two types of stimulatory cues on behaviors
      of human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells
      (HUVECs) were evaluated. Results showed that the nanostructure cues of
      electrospun nanofibers mainly affected cell morphology and cytoskeleton
      distribution while the chemistry cues of BG ion extracts played important roles
      in promoting cell proliferation. Both of the electrospun nanofiber structure and
      BG chemistry cues contributed to cell differentiation, including extracellular
      matrix synthesis of HDFs and vascularization of HUVECs. Interestingly, when the
      two kinds of stimulatory cues were applied together, obvious synergetic effects
      were observed as the combination of the two stimulatory cues showed the strongest
      stimulation effects on cell differentiation among all groups. Taken together, it
      is feasible to simultaneously apply two or more kinds of biomaterial stimulation
      signals to synergistically affect cell behaviors and enhance tissue regeneration,
      which is critical for instructing the design of tissue engineering scaffolds or
      biomaterial substrates with improved bioactivity.

PMID- 29017144
TI  - Anxiolytic effect of fatty acids and terpenes fraction from Aloysia triphylla:
      Serotoninergic, GABAergic and glutamatergic implications.
AB  - Aloysia triphylla (Verbenaceae) is an aromatic medicinal plant, and it is used
      for the treatment of "nervous" problems as, "sadness" and "nervousness". While,
      there are no reports about its pharmacological activity in animal models. The
      objective of this work was to evaluate the anxiolytic effect of the extracts and
      fractions of this species and to measure the interaction of the most active
      fraction with serotonergic, glutamatergic and GABAergic drugs. An elevated plus
      maze test was carried ought where the methanol (AtM), dicloromethane (AtD) and
      hexanic (AtH) extracts presented anxiolytic activity in mice when exposed to the
      test. Also, different fractions obtained from the AtD were evaluated (AtF1, AtF2
      and AtF3, 15mg/kg), and showed that fraction AtF1 possessed the anxiolytic
      activity, in the same model. Then, AtF1 was co-administered with different drugs,
      which act on GABAergic (bicuculline, picrotoxin, pentylenetetrazol, baclofen and
      phaclofen), or serotononinergic (DOI, 8-OH-DPAT, WAY 100635 and ketanserine) or
      glutamatergic (NMDA, MPEP and MK-801) systems. The anxiolytic activity of AtF1
      was modified by GABAergic and serotoninergic drugs. Chemical analysis of this
      fraction by using GC-MS, showed that it contains hexadecanoic acid, hexadecanoic
      acid methyl ester, octadecanoic acid methyl ester, eicosanoic acid methyl ester,
      vitamin E, alpha-amiryn, campesterol, sitosterol, stigmastan-2,22, dien-3-ol (4)
      and stigmasta 5, 24 (28) dien-3-ol.

PMID- 29017146
TI  - Fouling behavior of poly(ether)sulfone ultrafiltration membrane during
      concentration of whey proteins: Effect of hydrophilic modification using
      atmospheric pressure argon jet plasma.
AB  - The aim of the study was to investigate the effects of hydrophilic surface
      modification via atmospheric pressure jet plasma (ApJPls) on the fouling
      propensity of polyethersulfone (PES) ultrafiltration (UF) membranes during
      concentration of whey proteins. The distance from nozzle to substrate surface of
      30mm and the exposure period of 5 times were determined as the most effective
      parameters enabling an increase in DeltaGiwi value of the plain membrane from (-)
      14.92+/-0.89mJ/m2 to (+) 17.57+/-0.67mJ/m2. Maximum hydrophilicity and minimum
      surface roughness achieved by argon plasma action resulted in better antifouling
      behavior, while the hydraulic permeability and the initial permeate flux were
      decreased sharply due to the plasma-induced surface cross-linking. A quite steady
      state flux was obtained throughout the UF with the ApJPls modified PES membrane.
      The contribution of Rfrev to Rt, which was 94% for the UF through the plain
      membrane, decreased to 43% after the plasma treatment. The overall results of
      this study highlighted the ApJPls modification decreased the fouling propensity
      of PES membrane without affecting the original protein rejection capability and
      improved the recovery of initial permeate flux after chemical cleaning.

PMID- 29017147
TI  - Iontophoretic transdermal delivery using chitosan-coated PLGA nanoparticles for
      positively charged drugs.
AB  - Recently, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles prepared using a
      combination of an antisolvent diffusion method with preferential solvation was
      shown to be beneficial for the iontophoretic transdermal delivery of therapeutic
      agents. Also, this preparation method can contain a hydrophilic drug. However,
      since PLGA nanoparticles were negatively charged, it was difficult to apply
      iontophoresis for positively charged hydrophilic drugs. In this study, we
      prepared positively charged PLGA nanoparticles containing donepezil hydrochloride
      (DP). DP was used as a positively charged hydrophilic drug model. The PLGA
      nanoparticles were coated with chitosan hydroxypropyltrimonium chloride. The
      average particle diameter of the nanoparticles was 117.7+/-60.6nm and the surface
      charge number density changed from negative to positive. Ex vivo skin
      accumulation study was carried out using abdominal rat skin and a Franz-type
      diffusion cell with/without iontophoresis. When iontophoresis was applied, the DP
      concentration in the rat skin of chitosan-coated PLGA nanoparticles was 2.2 times
      higher than that of non-coated PLGA nanoparticles. This indicated that chitosan
      coated PLGA nanoparticles were suitable for iontophoresis. To investigate the
      transdermal delivery route of the nanoparticles, we prepared chitosan-coated PLGA
      nanoparticles containing DP, coumarin-6, and rhodamine 6G. Coumarin-6 and
      rhodamine 6G were used as a trace marker of the PLGA nanoparticles and positively
      charged hydrophilic drug model, respectively. From the results of ex vivo
      accumulation test of this fluorescent nanoparticles, it was suggested that
      positively charged hydrophilic drugs reached the hair follicles as a
      nanoparticle, and then they were released from the nanoparticles.

PMID- 29017148
TI  - Inhibition of neuronal autophagy mediates longevity.

PMID- 29017149
TI  - BubR1 and brain aging.

PMID- 29017150
TI  - Collection, Evaluation, and Coagulum Dissolution of Semen from Goeldi's Monkey,
      Callimico goeldii.
AB  - Research on Neotropical primates' reproduction is necessary due to the lack of
      available information and the increasing threat to these species. Callimico
      goeldii is listed as Vulnerable on the IUCN Red List of Threatened Species. This
      study aimed to test rectal electrostimulation for semen collection and evaluate
      seminal characteristics. Therefore, semen from 6 captive Goeldi's monkeys was
      collected and, for the first time, seminal characteristics are described.
      Coagulum formation was noted in all ejaculates, and we obtained partial or
      complete liquefaction of the samples. Results were (means +/- SD): volume = 26.9
      +/- 11.87 MUL; pH = 7.61 +/- 0.28; concentration = 143.18 +/- 174.96 * 106
      spermatozoa/mL; total sperm motility = 83.33 +/- 5.16%; linear progressive
      motility = 46 +/- 24.08%; plasma membrane integrity = 36.38 +/- 16.11%; acrosome
      integrity using fast-green/bengal-rose staining = 63.41 +/- 11.72%, and kit
      Spermac(r) = 69.36 +/- 11.81%; abnormal sperm = 72.5 +/- 17.7%, with 16.2 +/-
      7.7% major defects and 56.3 +/- 10% minor defects; sperm with high mitochondrial
      activity class I = 16.45 +/- 22.25%. Rectal electrostimulation was an efficient
      method for semen collection in this species. Investigations are required to
      improve semen collection and handling, including cryopreservation methods.

PMID- 29017151
TI  - The Clinical Significance of Physical Activity in Maintenance Dialysis Patients.
AB  - BACKGROUND: The aim of the present study was to evaluate the effects of physical
      activity on various aspects in Asian dialysis patients. METHODS: This was a
      retrospective cohort study. Study participants were recruited from 27 hospitals
      or dialysis centers in Korea (n = 1611). The participants were divided into 3
      groups according to the degree of regular exercise: Inactive group, Intermediate
      group, and Active group. RESULTS: The proportions of patients with frailty and
      the presence of each component decreased as physical activity increased. The
      presence and numbers of disabilities decreased as physical activity increased.
      The number of participants with a history of fall during the last 12 months was
      149 (20.5%) in the Inactive group, 88 (16.9%) in the Intermediate group, and 48
      (13.2%) in the Active group. Physical component scale and mental component scale
      scores increased as physical activity increased. The survival rate for all-cause
      death at 500 days was 95.5% in the Active group, 95.2% in the Intermediate group,
      and 93.5% in the Inactive group. CONCLUSION: High physical activity was
      associated with favorable results for most health-related quality of life scale
      scores, including frailty, disability, and exhaustion, in Korean dialysis
      patients.

PMID- 29017153
TI  - Bipolar Disorder and/or Creative Bipolarity: Robert Schumann's Exemplary
      Psychopathology - Combining Symptomatological and Psychosocial Perspectives with
      Creativity Research.
AB  - The psychopathological condition of Robert Schumann has been a prominent object
      of study in psychiatry since his hospitalization in 1854. Renowned psychiatrists
      have diagnosed Schumann with syphilis, schizophrenia, and bipolar and personality
      disorders. Until today, these analyses of his symptomatology have led to
      contradictory results. Recent discussion has suggested that his hospitalization
      was due to professional failure and separation wishes on the part of his wife,
      her family, and her friends. In line with this hypothesis is the opinion that the
      separation insisted upon by Clara Schumann was reinforced by the economic
      interests of the psychiatrist who kept Schumann in custody for 2 years until his
      death in 1856. In this article, we trace the complex interaction of bipolar
      vulnerability and pathogenic life events with hypersensitive talent and "creative
      bipolarity," defined as the capacity, motivation, and resilience to transform
      emotional stress and cognitive inconsistency into coherent artistic products.
      Finally, we present our conclusions about comprehensive psychiatric and
      psychotherapeutic treatment with respect to "creative bipolarity."

PMID- 29017152
TI  - High Uric Acid-Induced Epithelial-Mesenchymal Transition of Renal Tubular
      Epithelial Cells via the TLR4/NF-kB Signaling Pathway.
AB  - BACKGROUND: Hyperuricemia is an independent risk factor for causing chronic
      kidney disease and contributes to kidney fibrosis. After urate crystals get
      deposited in the kidney, they can cause hyperuricemia nephropathy, leading to
      glomerular hypertrophy and renal tubular interstitial fibrosis. Recent data
      showed that uric acid (UA) could induce epithelial mesenchymal transition (EMT)
      of renal tubular cells, in which NRLP3 inflammatory pathway was involved.
      However, whether TLR4/NF-kappaB signaling pathway is also involved in EMT of
      renal tubular cells induced by UA is not clear. METHODS: Human renal tubular
      epithelial cells (HK-2) were directly treated with UA and the phenotypic
      transition was detected by morphological changes and the molecular markers of
      EMT. The activation of the TLR4/NF-kappaB signaling pathway induced by UA was
      measured by Western blot and its involvement was further confirmed by the
      inhibition of NF-kappaB activation or knockdown of toll like receptor 4 (TLR4)
      expression. RESULTS: UA induced obvious morphological changes of HK-2 cell,
      accompanied with altered molecular markers of EMT including fibronectin, alpha
      SMA and E-cadherin. In addition, UA significantly upregulated the gene expression
      of interleukin-1beta and tumor necrosis factor-alpha in a time- and dose
      dependent manner. Furthermore, UA significantly activated the TLR4/NF-kappaB
      signaling pathway in HK-2 cells, while the inhibition of the TLR4 expression by
      siRNA and NF-kappaB activation by PDTC significantly attenuated EMT induced by UA
      in HK-2 cells. CONCLUSIONS: UA can induce EMT in renal tubular epithelial cells
      by the activation of the TLR4/NF-kappaB signaling pathway, and the targeted
      intervention of the TLR4/NF-kappaB signaling pathway might effectively inhibit UA
      induced renal interstitial fibrosis mediated by EMT.

PMID- 29017154
TI  - Screening Performance of Placental Growth Factor for the Prediction of Low Birth
      Weight and Adverse Intrapartum and Neonatal Outcomes in a Term Low-Risk
      Population.
AB  - INTRODUCTION: Fetuses who fail to reach their genetic growth potential are
      thought to have sub-optimal placental function. Low placental growth factor
      (PlGF) levels have been shown to be predictive of placentally mediated
      conditions, such as pre-eclampsia or fetal growth restriction. We investigated
      the screening performance of PlGF for the prediction of low birth weight (<10th
      centile for gestation) and adverse intrapartum and neonatal outcomes in
      apparently low-risk term pregnancies. MATERIALS AND METHODS: Maternal PlGF levels
      were measured fortnightly in a blinded, prospective, observational study from 36
      weeks of pregnancy. Women and clinicians were blinded to PlGF results, and
      pregnancies were managed according to local policies and guidelines. Intrapartum
      and neonatal outcomes were recorded. PlGF was analysed for association with, and
      predictive capacity for, low birth weight, caesarean section for intrapartum
      fetal compromise (CS-IFC) and adverse neonatal outcomes. RESULTS: A total of 438
      women were included in the final analysis. Lower PlGF levels were associated with
      low birth weight, CS-IFC and adverse neonatal outcome. For a false-positive rate
      of 10 and 20%, respectively, the corresponding sensitivities were 9.7-11.1% and
      22.2-26.8%. CONCLUSION: As a sole predictor for low birth weight, CS-IFC and
      adverse neonatal outcome, PlGF was poor as a test.

PMID- 29017155
TI  - Effectiveness of IHD with Adsorptive PMMA Membrane in Myeloma Cast Nephropathy: A
      Cohort Study.
AB  - BACKGROUND: In patients with cast nephropathy and acute kidney injury (AKI)
      requiring dialysis, the reduction of serum free light chains (FLC) using
      chemotherapy and intensive hemodialysis (IHD) with a high cut-off filter may
      improve renal and patient outcomes. We evaluated the effectiveness of a
      combination of chemotherapy and IHD with an adsorbent polymethylmethacrylate
      membrane (IHD-PMMA) on renal recovery and survival. METHODS: A single-center
      retrospective cohort-study was conducted. Between 2007 and 2014, patients with
      dialysis-dependent acute cast nephropathy treated with chemotherapy and IHD-PMMA
      were included. Patients had six 6-h hemodialysis sessions a week, until
      predialysis serum FLC fell below 200 mg/L, for a maximum of 3 weeks. Primary
      outcomes were renal recovery, defined as dialysis independence, and survival.
      RESULTS: Seventeen patients were included, all with stage 3 AKI. All received
      chemotherapy, mostly based on bortezomib and steroids (88%). Twelve patients
      (71%) achieved renal recovery, usually within 60 days (92%). At 3 months, the
      overall hematological response rate was 57%; hematological response was
      maintained for at least 2 years in 86% of responders. At 6, 12, and 24 months,
      76, 75, and 62% of patients were alive, respectively. Higher reduction in
      involved FLC by day 12 (p = 0.022) and day 21 (p = 0.003) was associated with
      renal recovery. Patients with FLC reduction rate >50% by day 21 experienced a
      lower mortality (hazard ratio 0.10, 95% CI 0.02-0.63). CONCLUSION: In patients
      with dialysis-dependent myeloma cast nephropathy, early FLC removal by IHD-PMMA
      combined with chemotherapy was associated with high rates of renal recovery and
      survival.

PMID- 29017157
TI  - Impact of the Number of Metastatic Tumors Treated by Stereotactic Radiosurgery on
      the Dose to Normal Brain: Implications for Brain Protection.
AB  - PURPOSE/OBJECTIVES: The purpose of this study was to evaluate the effect of the
      number of brain lesions for which stereotactic radiosurgery (SRS) was performed
      on the dose volume relationships in normal brain. MATERIALS AND METHODS: Brain
      tissue was segmented using the patient's pre-SRS MRI. For each plan, the
      following data points were recorded: total brain volume, number of lesions
      treated, volume of brain receiving 8 Gy (V8), V10, V12, and V15. RESULTS: A total
      of 225 Gamma Knife(r) treatments were included in this retrospective analysis.
      The number of lesions treated ranged from 1 to 29. The isodose for prescription
      ranged from 40 to 95% (mean 55%). The mean prescription dose to tumor edge was 18
      Gy. The mean coverage, selectivity, conformity, and gradient index were 97.5%,
      0.63, 0.56, and 3.5, respectively. The mean V12 was 9.5 cm3 (ranging from 0.5 to
      59.29). There was no correlation between the number of lesions and brain V8, V12,
      V10, or V15. There was a direct and statistically significant relationship
      between the brain volume treated (V8, V10, V12, and V15) and total volume of
      tumors treated (p < 0.001). In our study, the integral dose to the brain exceeded
      3 J when the total tumor volume exceeded 25 cm3. CONCLUSIONS: The number of
      metastatic brain lesions treated bears no significant relationship to total brain
      tissue volume treated when using SRS. The fact that the integral dose to the
      brain exceeded 3 J when the total tumor volume exceeded 25 cm3 is useful for
      establishing guidelines. Although standard practice has favored using whole brain
      radiation therapy in patients with more than 4 lesions, a significant amount of
      normal brain tissue may be spared by treating these patients with SRS. SRS should
      be carefully considered in patients with multiple brain lesions, with the
      emphasis on total brain volume involved rather than the number of lesions to be
      treated.

PMID- 29017156
TI  - The Missing Link in the Pathophysiology of Vascular Cognitive Impairment: Design
      of the Heart-Brain Study.
AB  - BACKGROUND: Hemodynamic balance in the heart-brain axis is increasingly
      recognized as a crucial factor in maintaining functional and structural integrity
      of the brain and thereby cognitive functioning. Patients with heart failure (HF),
      carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present
      themselves with complaints attributed to specific parts of the heart-brain axis,
      but hemodynamic changes often go beyond the part of the axis for which they
      primarily seek medical advice. The Heart-Brain Study hypothesizes that the
      hemodynamic status of the heart and the brain is an important but underestimated
      cause of VCI. We investigate this by studying to what extent hemodynamic changes
      contribute to VCI and what the mechanisms involved are. Here, we provide an
      overview of the design and protocol. METHODS: The Heart-Brain Study is a
      multicenter cohort study with a follow-up measurement after 2 years among 645
      participants (175 VCI, 175 COD, 175 HF, and 120 controls). Enrollment criteria
      are the following: 1 of the 3 diseases diagnosed according to current guidelines,
      age >=50 years, no magnetic resonance contraindications, ability to undergo
      cognitive testing, and independence in daily life. A core clinical dataset is
      collected including sociodemographic factors, cardiovascular risk factors,
      detailed neurologic, cardiac, and medical history, medication, and a physical
      examination. In addition, we perform standardized neuropsychological testing,
      cardiac, vascular and brain MRI, and blood sampling. In subsets of participants
      we assess Alz-heimer biomarkers in cerebrospinal fluid, and assess
      echocardiography and 24-hour blood pressure monitoring. Follow-up measurements
      after 2 years include neuropsychological testing, brain MRI, and blood samples
      for all participants. We use centralized state-of-the-art storage platforms for
      clinical and imaging data. Imaging data are processed centrally with automated
      standardized pipelines. RESULTS AND CONCLUSIONS: The Heart-Brain Study
      investigates relationships between (cardio-)vascular factors, the hemodynamic
      status of the heart and the brain, and cognitive impairment. By studying the
      complete heart-brain axis in patient groups that represent components of this
      axis, we have the opportunity to assess a combination of clinical and subclinical
      manifestations of disorders of the heart, vascular system and brain, with
      hemodynamic status as a possible binding factor.

PMID- 29017159
TI  - Picrasidine I from Picrasma Quassioides Suppresses Osteoclastogenesis via
      Inhibition of RANKL Induced Signaling Pathways and Attenuation of ROS Production.
AB  - BACKGROUND/AIMS: Osteoporosis is a metabolic bone disorder that tortures about
      millions of people worldwide. Recent study demonstrated agents derived from
      picrasma quassioides is a promising drug for targets multiple signaling pathways.
      However its potential in treatment of bone loss has not been fully understood.
      METHODS: The bone marrow macrophages (BMMs) were cultured and induced with M-CSF
      and RANKL followed by picrasidine I (PI) treatment. Then the effects of PI on
      osteoclast formation were evaluated by counting tartrate-resistant acid
      phosphatase (TRAP)-positive multinucleated cells. Moreover, effects of PI on bone
      resorption activity of mature osteoclast were studied through bone resorption pit
      counting and actin ring structure analysis. Further, the involved potential
      signaling pathways cross-talking were investigated by performed Western blotting
      and quantitative real-time PCR examination. RESULTS: Results demonstrated PI
      strongly inhibited RANKL induced osteoclast formation from its precursors.
      Mechanistically, the inhibitory effect of PI on osteoclast differentiation was
      due to the suppression of osteoclastogenic transcription factors, c-Fos and
      NFATc1. Moreover, PI markedly blocked the RANKL-induced osteoclastogenesis by
      attenuating MAPKs and NF-kappaB signaling pathways. In addition, PI decreased the
      ROS generation in osteoclast and osteoblast. CONCLUSION: Taken together our data
      demonstrate that PI has antiosteoclastogenic effect by inhibiting inflammation
      induced activation of MAPKs, NF-kappaB and ROS generation followed by suppressing
      the gene expression of c-Fos and NFATc1 in osteoclast precursors.

PMID- 29017158
TI  - Beneficial Effects of n-3 Fatty Acids on Cardiometabolic and Inflammatory Markers
      in Type 2 Diabetes Mellitus: A Clinical Trial.
AB  - OBJECTIVE: To determine the effect of supplementation with n-3 polyunsaturated
      fatty acids (PUFAs) on circulatory resistin and monocyte chemoattractant protein
      1 (MCP-1) levels in type 2 diabetes mellitus (T2DM) patients. SUBJECTS AND
      METHODS: This was a 10-week, placebo-controlled, double-blind, randomized trial
      of n-3 PUFAs (2,700 mg/day) versus placebo (soft gels containing 900 mg of edible
      paraffin). Forty-four T2DM patients were supplemented with n-3 PUFAs and another
      44 patients received placebo (3 patients discontinued the trial). Serum resistin,
      MCP-1, and the lipid profile were measured before and after supplementation. The
      adiponectin-resistin index (1 + log10 [resistin] - log10 [adiponectin]) and
      atherogenic index (log10 triglyceride/high-density lipoprotein cholesterol) of
      plasma (an indicator of cardiovascular complications) were assessed. The
      independent Student t test was used to assess the differences between the
      supplement and placebo groups and the paired t test to analyze the before/after
      changes. RESULTS: In this study, n-3 PUFAs reduced serum MCP-1 levels (from 260.5
      to 230.5 pg/mL; p = 0.002), but they remained unchanged in the placebo group. n-3
      PUFAs could not decrease serum resistin levels. The adiponectin-resistin index
      was significantly reduced after supplementation with n-3 PUFAs when compared to
      the placebo. The atherogenic index was also significantly improved after
      supplementation with n-3 PUFAs (from 1.459 to 1.412; p = 0.006). CONCLUSIONS: The
      MCP-1 levels and lipid profile were improved after supplementation with n-3
      PUFAs, but resistin serum levels were not changed. Hence, the anti-inflammatory
      effects of n-3 PUFAs might be mediated by targeting MCP-1.

PMID- 29017160
TI  - Role of Molecular Biology in Diagnosis and Characterization of Vulvo-Vaginitis in
      Clinical Practice.
AB  - The diagnosis of vulvo-vaginal complaints has always been enigmatic in obstetrics
      and gynecology. Patients with clear, pathognomonic symptoms end up with a proper
      diagnosis and treatment most of the time, but unfortunately we are now living in
      a world where women reach out to the Internet and readily get all information as
      to which disease their symptoms correspond to and also find the appropriate
      treatment "over-the-counter." Because of this trend, we as specialists are
      increasingly confronted with patients with complex and combined conditions. At
      the same time, extremely sensitive and accurate diagnostic tools are now being
      developed at a rapid pace, allowing the physicians to diagnose vulvo-vaginal
      disease with a substantially increased precision. Moreover, many of these
      molecular biology (MB)-based tests have become so common and affordable that self
      sampling and self-testing are no longer utopia. On the other hand, too much
      information that is too readily available and that is too affordable also
      encompasses pitfalls, leading to gross overtreatment and psychological burden. As
      experienced caregivers, we should supervise these evolutions, define their place
      and proper use as diagnostic tools, utilize their potential as ad hoc tools to
      follow-up treatment efficacy and guide how such tools can be used for responsible
      self-testing. In the present paper, responding to the need for appropriate,
      quality assured and accessible tests for vulvo-vaginitis and the huge potential
      delivered by the rapidly developing MB methods, we recommend the need for a broad
      and regular discussion forum, composed of both clinical and technical experts and
      opinion makers, in order to match the needs with the huge opportunities and
      ideally combine the initiatives and forces into the same direction. This forum
      should then translate conceived strategies into regularly updated, evidence-based
      national and international guidelines.

PMID- 29017161
TI  - Prognostic Factors for Survival in Patients with Advanced Intrahepatic
      Cholangiocarcinoma Treated with Gemcitabine plus Cisplatin as First-Line
      Treatment.
AB  - OBJECTIVES: Intrahepatic cholangiocarcinoma (ICC) is a rare type of liver cancer.
      No clinically useful prognostic factors have been reported for patients with
      advanced ICC. In the present study, we aimed to evaluate the clinical prognostic
      factors of patients with advanced ICC receiving gemcitabine plus cisplatin
      combination therapy (GC) as standard first-line chemotherapy. METHODS: A
      retrospective analysis was performed of the data of patients with ICC treated at
      our institution from March 2011 to January 2016. We used the Cox regression model
      and estimated the hazard ratios of potential prognostic factors for survival.
      RESULTS: Of 216 patients with biliary tract cancer receiving GC as first-line
      chemotherapy, we extracted data for 77 patients who were diagnosed with ICC and
      received GC as first-line chemotherapy. The median overall survival was 13.8
      months (95% CI, 8.9-18.6). In multivariate analysis, pretreatment serum lactate
      dehydrogenase (hazard ratio [HR]: 2.53, p = 0.005), C-reactive protein (HR: 3.06,
      p = 0.001), and carcinoembryonic antigen (HR: 2.39, p = 0.03) levels were
      significantly associated with overall survival. CONCLUSIONS: Readily available
      clinical laboratory values reliably predicted the prognosis of ICC patients
      receiving GC therapy. If validated in other studies, these results may provide a
      useful tool for individual patient-risk evaluation and the design and
      interpretation of future trials.

PMID- 29017164
TI  - Aspirin Prophylaxis for Migraine with Aura: An Observational Case Series.

PMID- 29017163
TI  - pTis and pT1a Ipsilateral Breast Tumor Recurrence Is Associated with Good
      Prognosis after Salvage Surgery.
AB  - OBJECTIVES: Patients with ipsilateral breast tumor recurrence (IBTR) after breast
      conserving surgery have a poor prognosis. There is little information regarding
      the prognostic impact of the tumor size in patients with IBTR. METHODS: A total
      of 143 patients who had histologically confirmed IBTR without distant metastases
      and who underwent salvage surgery between 1989 and 2013 in our hospital were
      included. Distant disease-free survival (DDFS) was calculated according to the
      invasive tumor size of IBTR. The median follow-up period was 4.6 years. RESULTS:
      Patients with pT1b or more advanced IBTR have a high (>=20%) 5-year distant
      recurrence risk. There were significant differences in DDFS between patients with
      pTis or pT1a and those with pT1b or a more advanced stage (5-year DDFS: 94.4 vs.
      70.1%, respectively, p value = 0.006). This significance remained after adjusting
      for other clinicopathological factors (p value = 0.04). CONCLUSION: Patients with
      pTis or pT1a IBTR have a good prognosis after salvage surgery for IBTR, and the
      omission of adjuvant chemotherapy could be considered. Further research and
      validation studies are needed.

PMID- 29017162
TI  - Patiromer Lowers Serum Potassium When Taken without Food: Comparison to Dosing
      with Food from an Open-Label, Randomized, Parallel Group Hyperkalemia Study.
AB  - BACKGROUND: Patiromer is a sodium-free, nonabsorbed, potassium binder approved
      for treatment of hyperkalemia. This open-label study compares the efficacy and
      safety of patiromer administered without food versus with food. METHODS: Adults
      with hyperkalemia (potassium >=5.0 mEq/L) were randomized (1:1) to receive
      patiromer once daily without food or with food for 4 weeks. The dosage was
      adjusted (maximum: 25.2 g/day) using a prespecified titration schedule to achieve
      and maintain potassium within a target range (3.8-5.0 mEq/L). The primary
      efficacy endpoint was the proportion of patients with serum potassium in the
      target range at either week 3 or week 4. Safety was assessed by adverse events
      (AEs) and laboratory testing. RESULTS: Efficacy was evaluated in 112 patients;
      65.2% were >=65 years of age, 75.9% had chronic kidney disease, and 82.1% had
      diabetes. Baseline mean serum potassium was similar in the without-food (5.44
      mEq/L) and with-food (5.34 mEq/L) groups. The primary endpoint was achieved by
      87.3% (95% CI 75.5-94.7) and 82.5% (95% CI 70.1-91.3) of patients in the with
      food and without-food groups, respectively; least squares mean changes in serum
      potassium from baseline to week 4 were -0.65 and -0.62 mEq/L, respectively (p <
      0.0001). The most common AEs were diarrhea and constipation. Serum K+ remained
      >=3.5 mEq/L in all patients; 5 patients developed serum magnesium <1.4 mg/dL,
      including 4 whose baseline magnesium was below the lower limit of normal.
      CONCLUSION: Patiromer is equally effective and well tolerated when taken without
      food or with food, thereby offering the potential for dosing flexibility.

PMID- 29017165
TI  - Feasibility of Segmental Colectomy Followed by Endoscopic Surveillance as a
      Treatment Strategy for Colorectal Cancer Patients with Lynch Syndrome.
AB  - BACKGROUND: Initial surgical procedures for colorectal cancer (CRC) patients with
      Lynch syndrome remain controversial. This study assessed the validity of
      segmental colectomy (SGC) followed by endoscopic surveillance as a treatment
      strategy for CRC patients with Lynch syndrome. METHODS: Among consecutive
      patients who underwent surgery for primary CRC between April 1985 and December
      2014, 49 patients were observed to have germline mutations in a mismatch repair
      gene, and 38 patients who underwent SGC followed by periodic endoscopic
      surveillance at our institution were evaluated for metachronous CRC, need for
      secondary surgery, and the details of endoscopic surveillance. RESULTS: Of the 38
      patients who underwent SGC followed by periodic endoscopic surveillance at our
      institution, 6 (15.8%) patients showed metachronous CRC, 3 (7.9%) patients
      underwent endoscopic resection, and the other 3 patients (7.9%) underwent
      secondary surgery. The dispersion of the endoscopic surveillance interval was
      significantly greater in patients with metachronous CRC (364 +/- 332.9 days) than
      in those without metachronous CRC (370 +/- 129.7 days; p < 0.001). CONCLUSIONS:
      SGC followed by annual endoscopic surveillance was feasible as a treatment
      strategy for CRC patients with Lynch syndrome, because the incidence of
      metachronous CRC and the need for secondary surgery were low. Annual and periodic
      endoscopic surveillance might be essential for early detection of metachronous
      CRC and prevention of secondary surgery because of metachronous CRC in CRC
      patients with Lynch syndrome after SGC.

PMID- 29017167
TI  - Hopes and Difficulties for Blastocyst Complementation.
AB  - CONTEXT: The clinical need for organ replacement therapies has inspired the idea
      of growing human organs in animal hosts. The injection of human pluripotent stem
      cells into animal blastocysts provides a possible strategy to accomplish this
      goal. Subject of Review: A recent study [Wu et al. Cell 2017;168:473-486.e415]
      tests the feasibility of this approach by creating chimeric embryos between
      humans and large domestic animals, including pigs and cattle. The study further
      examines the potential of combining CRISPR-Cas9 gene editing with blastocyst
      complementation to grow fully foreign organs in chimeric hosts. Second Opinion:
      Here, we consider what this report and related studies reveal about the
      likelihood of human-animal chimeras reaching the clinic and translating into
      therapies. A careful look suggests hope for eventual success in this area but
      also underscores important challenges that will require dedicated effort to
      resolve.

PMID- 29017166
TI  - The Role of the Mineralocorticoid Receptor in Inflammation: Focus on Kidney and
      Vasculature.
AB  - BACKGROUND: The remarkable success of clinical trials in mineralocorticoid
      receptor (MR) inhibition in heart failure has driven research on the
      physiological and pathological role(s) of nonepithelial MR expression. MR is
      widely expressed in the cardiovascular system and is a major determinant of
      endothelial function, smooth muscle tone, vascular remodeling, fibrosis, and
      blood pressure. An important new dimension is the appreciation of the role MR
      plays in immune cells and target organ damage in the heart, kidney and
      vasculature, and in the development of insulin resistance. SUMMARY: The mechanism
      for MR activation in tissue injury continues to evolve with the evidence to date
      suggesting that activation of MR results in a complex repertoire of effects
      involving both macrophages and T cells. MR is an important transcriptional
      regulator of macrophage phenotype and function. Another important feature of MR
      activation is that it can occur even with normal or low aldosterone levels in
      pathological conditions. Tissue-specific conditional models of MR expression in
      myeloid cells, endothelial cells, smooth muscle cells and cardiomyocytes have
      been very informative and have firmly demonstrated a critical role of MR as a key
      pathophysiologic variable in cardiac hypertrophy, transition to heart failure,
      adipose inflammation, and atherosclerosis. Finally, the central nervous system
      activation of MR in permeable regions of the blood-brain barrier may play a role
      in peripheral inflammation. Key Message: Ongoing clinical trials will help
      clarify the role of MR blockade in conditions, such as atherosclerosis and
      chronic kidney disease.

PMID- 29017168
TI  - Enhanced at Puberty-1 (Eap1) Expression Critically Regulates the Onset of Puberty
      Independent of Hypothalamic Kiss1 Expression.
AB  - BACKGROUND/AIMS: Enhance at puberty-1 (Eap1) is an intronless gene that regulates
      the onset of puberty through a network of hypothalamic genes. However, precise
      mechanistic events essential for Eap1-regulation of puberty have not been fully
      elucidated. Eap1 is thought to promote the initiation of puberty through
      regulation of the hypothalamic metastasis-suppressor KiSS1. We aim to investigate
      this hypothesis by genetically perturbing Eap1 through RNA interference in vivo.
      METHODS: We first engineered and optimized four sets of shRNAs that target rat
      Eap1 mRNA as well as one negative control shRNA. After generating lentiviral (LV)
      particles, we examined the suppression of Eap1 in NRK-54E cell line to select the
      most efficient one. Sequencelly, LV-Eap1-shRNA or controls including LV-eGFP and
      saline were intraventricular microinjected into 21-day-old rats. Rats were raised
      in appropriate conditions and we examined the time of vaginal opening, ovary
      physiology as well as hypothalamic puberty-regulatory genes at three
      developmental stages: juvenile (postnatal day PND25), early puberty (PND35),
      adult (PND42). RESULTS: Hypothalamic suppression of Eap1 delayed the onset of rat
      vaginal opening. Hematoxylin and eosin (H&E) staining revealed a significant
      reduction of corpus luteum (CL) at PND35, but at PND42 CL levels were normal
      relative to control. In conjunction with differences in phenotype and ovary
      morphology, GnRH expression and transcripts were also reduced at PND25 and PND35,
      while their levels were similar to control at PND42. KiSS1 mRNA and protein
      levels were not significantly different at all three developmental stages.
      CONCLUSION: Eap1 expression critically regulates puberty as well as GnRH
      expression. However, Eap1-regulation of puberty may not necessitate KiSS1/GPR54
      signaling.

PMID- 29017169
TI  - Ox-LDL-Induced MicroRNA-155 Promotes Autophagy in Human Endothelial Cells via
      Repressing the Rheb/ mTOR Pathway.
AB  - BACKGROUND/AIMS: Autophagy, an evolutionary conserved biological process, is
      activated in cells to cope with various types of stress. MicroRNAs control
      several activities related to autophagy. However, the role of autophagy-related
      microRNAs during atherosclerosis is far from known. MicroRNA-155 was identified
      to be a crucial regulator of atherosclerosis. The objectives of the study were to
      analyze the effect of microRNA-155 on autophagic signaling and explore its
      mechanism in human endothelial cells under ox-LDL stress. METHODS: The study
      included human endothelial cells surrogate EA.hy926 lines (EA.hy926 cells). The
      expression of microRNA-155 was analyzed by quantitative reverse transcription
      polymerase chain reaction (qRT-PCR). The effect of microRNA-155 on endothelial
      autophagy was observed along with the expression levels of Rheb, LC3B, Beclin1,
      and P62/SQSTM1 by western blotting (WB) and immunofluorescence through microRNA
      155 overexpression or inhibition. Bioinformatics analysis and Luciferase reporter
      assay were used to explore the target gene of microRNA-155. Cell viability and
      apoptosis were examined by 3-[4,5-dimethylthiazol-2-yl]-5- [3-carboxy
      methoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium inner salt (MTS) assay and TdT
      mediated dUTP Nick-End Labeling (TUNEL) apoptosis assay. RESULTS: MicroRNA-155
      expression was significantly increased under ox-LDL stress. MicroRNA-155
      increased autophagic activity, while inhibition of it alleviated ox-LDL-induced
      autophagy in EA.hy926 endothelial cells. In addition, dual-luciferase reporter
      assays showed that microRNA-155 suppressed Rheb transcription. MicroRNA-155
      increased autophagic activity in EA.hy926 cells via inhibition of Rheb-mediated
      mTOR/P70S6kinase/4EBP signaling pathway. Furthermore, we demonstrated that
      microRNA-155 could regulate not only autophagy but also apoptosis in EA.hy926
      cells. CONCLUSIONS: MicroRNA-155 works as a regulator of endothelial function
      under ox-LDL stress, making it a potential candidate for the novel therapeutic
      strategies against atherosclerotic diseases.

PMID- 29017170
TI  - Impact of Typhoon Haiyan on a Philippine Tarsier Population.
AB  - Over the last 2 decades the Philippine tarsier (Carlito syrichta aka Tarsius
      syrichta) has had its conservation status revised from Endangered to Data
      Deficient to Near Threatened. The last status change was based on a study of the
      species' population density, which suggested that a single natural catastrophe
      could potentially wipe out the Philippine tarsier. In 2013 typhoon Haiyan hit
      Bohol, one of the island strongholds for this species. In this study we compare
      the density of the Bohol tarsier population within the Philippine Tarsier and
      Wildlife Sanctuary before and after the typhoon. We demonstrate that the typhoon
      significantly affected the density of the Philippine tarsier in the sanctuary.
      Before the typhoon, tarsier density was approximately 157 individuals/km2 whereas
      after the typhoon the density was a mere 36 individuals/km2. Prior to the
      typhoon, more Philippine tarsiers were found in older secondary forest than in
      younger secondary forest, whereas after the typhoon all observed individuals were
      found in relatively younger secondary forest. Vegetation plots where we observed
      Philippine tarsiers prior to the typhoon contained a mean of 33 trees/m2, with a
      mean diameter at breast height (DBH) of 24 cm, and a mean height of 4 m. After
      the typhoon vegetation plots contained an average of 156 trees, had a mean DBH of
      6 cm, and a mean height of 2 m. Based on the IUCN Red List criteria, the
      reduction and fluctuation in the density of this species suggests that the
      conservation status of the Philippine tarsier should be changed to Vulnerable.
      This study indicates natural disasters can have a significant effect on the
      extinction risk of primates, with implications for future effects of
      anthropogenic climate change.

PMID- 29017171
TI  - Role of the TGFbeta/PDCD4/AP-1 Signaling Pathway in Nasopharyngeal Carcinoma and
      Its Relationship to Prognosis.
AB  - BACKGROUND: The objective of the present study was to evaluate the role of the
      TGFbeta/PDCD4/AP-1 pathway in nasopharyngeal carcinoma (NPC) and its relationship
      to NPC prognosis. METHODS: NPC tissues collected from 66 NPC patients were
      compared to 17 nasopharyngeal mucosa biopsy specimens collected as normal
      tissues. Immunohistochemical staining was performed to assess expression of
      transforming growth factor-beta receptor I (TGFbetaRI), programmed cell death 4
      (PDCD4) and activator protein-1 (AP-1). The Kaplan-Meier method was applied to
      evaluate NPC patient overall survival (OS) and progression-free-survival (PFS).
      Cox regression analysis was used to estimate independent prognostic factors for
      NPC. The human NPC cell line CNE2 was selected and treated with SB431542, an
      inhibitor of TGFbetaRI; expression of TGFbetaRI and PDCD4 in CNE2 cells was
      determined by western blotting. NPC tissues showed higher expression of TGFbetaRI
      and AP-1 but lower expression of PDCD4 than normal tissues (all P < 0.05).
      RESULTS: The results of Kaplan-Meier analysis showed that TGFbetaRI-positive
      patients and AP-1-positive patients had shorter OS and PFS than TGFbetaRI
      negative patients and AP-1-negative patients; additionally, PDCD4-positive
      patients had higher OS and PFS than PDCD4-negative patients. Cox regression
      analysis revealed that advanced tumor stage, overexpression of TGFbetaRI and AP
      1, and low expression of PDCD4 were unfavorable factors influencing OS and PFS in
      NPC patients. Compared with the control group, expression of TGFbetaRI decreased
      and that of PDCD4 increased significantly in CNE2 cells treated with the
      inhibitor (all P < 0.05). These findings indicate that the TGFbeta/PDCD4/AP-1
      pathway may be associated with NPC development and progression. CONCLUSION: High
      expression of TGFbetaRI and AP-1 and low expression of PDCD4 may be unfavorable
      prognostic factors for NPC.

PMID- 29017172
TI  - The Emerging Roles of CIB1 in Cancer.
AB  - Calcium and integrin-binding protein 1 (CIB1) is an EF-hand calcium binding
      protein, which is involved in many cellular processes, including calcium
      signaling, cell survival and proliferation, cell migration, cell adhesion and
      apoptosis. A number of studies have found that CIB1 is ubiquitously expressed and
      is related to various human diseases, such as cancer, Alzheimer's disease (AD),
      cardiac hypertrophy and male infertility. The mechanism of CIB1 in human diseases
      is still not clear, although multiple functions of CIB1 are modulated by
      interacting with numerous interacting partners. As a calcium binding protein, the
      roles of CIB1 in calcium signaling by binding calcium or modulating some key
      modulators, such as calcineurin, integrin, inositol 1,4,5-trisphosphate receptor
      (IP3R) and taste 1 receptor member 2 (TAS1R2). The tumor promoting mechanisms of
      CIB1 have been described in different aspects, including promoting tumor cell
      cycle and proliferation, inhibiting tumor cell apoptosis, and mediating tumor
      cell migration and angiogenesis. In addition, multiple functions of CIB1, such as
      neural development, taste or gustation functions, and virus infection are also
      elucidated. These recent advances have significantly expanded our understanding
      of the knowledge of CIB1 and highlighted the potential mechanisms of CIB1 in
      tumor progression.

PMID- 29017173
TI  - Insulin Regimens to Treat Hyperglycemia in Hospitalized Patients on Nutritional
      Support: Systematic Review and Meta-Analyses.
AB  - BACKGROUND: The best insulin regimen to treat hyperglycemia in hospitalized
      patients on nutritional support (NS) is unclear. METHODS: We searched electronic
      databases to identify cohort studies or randomized clinical trials in order to
      evaluate the efficacy of different insulin regimens used to treat hyperglycemia
      in hospitalized patients on NS on diverse outcomes: mean blood glucose (MBG),
      hypoglycemia, length of stay in hospital, and mortality. RESULTS: Seventeen
      studies from a total of 5,030 were included. Enteral Group included 8 studies;
      1,203 patients using rapid, glargine, NPH, or Premix insulin; MBG 108-225 mg/dL;
      hypoglycemia 0-13%. In indirect meta-analyses, NPH insulin ranked best for
      glucose control (MD 95% CI -2.50 mg/dL [2.65 to -2.35]). Parenteral Group
      included 4 studies; 228 patients using regular and glargine or NPH insulin; MBG
      137-202 mg/dL; hypoglycemia 0-40%. In meta-analyses comparing regular insulin
      added to parenteral nutrition bag with glargine, MBG (MD 95% CI -3.78 mg/dL [
      11.93 to 4.37]; I2 = 0%) or hypoglycemia frequency (RR 95% CI 1.37 [0.43-4.32];
      I2 = 70.7%) did not differ. The description related to hospital length of stay
      and mortality was inconsistent between groups. CONCLUSIONS: The best insulin
      regimen to treat hyperglycemia in hospitalized patients on NS has not been
      established; best results using insulin regimens with NPH in enteral nutrition do
      not seem to be clinically relevant.

PMID- 29017174
TI  - Cardiac Remodeling Induced by All-Trans Retinoic Acid is Detrimental in Normal
      Rats.
AB  - BACKGROUND/AIMS: This study aimed to discern whether the cardiac alterations
      caused by retinoic acid (RA) in normal adult rats are physiologic or pathologic.
      METHODS AND RESULTS: Wistar rats were assigned into four groups: control animals
      (C, n = 20) received a standard rat chow; animals fed a diet supplemented with
      0.3 mg/kg/day all-trans-RA (AR1, n = 20); animals fed a diet supplemented with 5
      mg/kg/day all-trans-RA (AR2, n = 20); and animals fed a diet supplemented with 10
      mg/kg/day all-trans-RA (AR3, n = 20). After 2 months, the animals were submitted
      to echocardiogram, isolated heart study, histology, energy metabolism status,
      oxidative stress condition, and the signaling pathway involved in the cardiac
      remodeling induced by RA. RA increased myocyte cross-sectional area in a dose
      dependent manner. The treatment did not change the morphological and functional
      variables, assessed by echocardiogram and isolated heart study. In contrast, RA
      changed catalases, superoxide dismutase, and glutathione peroxidases and was
      associated with increased values of lipid hydroperoxide, suggesting oxidative
      stress. RA also reduced citrate synthase, enzymatic mitochondrial complex II, ATP
      synthase, and enzymes of fatty acid metabolism and was associated with increased
      enzymes involved in glucose use. In addition, RA increased JNK 1/2 expression,
      without changes in TGF-beta, PI3K, AKT, NFkappaB, S6K, and ERK. CONCLUSION: In
      normal rats, RA induces cardiac hypertrophy in a dose-dependent manner. The non
      participation of the PI3K/Akt pathway, associated with the participation of the
      JNK pathway, oxidative stress, and changes in energy metabolism, suggests that
      cardiac remodeling induced by RA supplementation is deleterious.

PMID- 29017176
TI  - Oxygen-ozone autohemotherapy in sacroiliitis.

PMID- 29017175
TI  - Body Weight Changes after Deep Brain Stimulation for Obsessive-Compulsive
      Disorder or Depression.
AB  - BACKGROUND: In 2010, we published an often-cited case report describing smoking
      cessation and substantial weight loss after deep brain stimulation (DBS) for
      obsessive-compulsive disorder (OCD) in an obese patient. To test whether this
      single observation was also observed in the treated population at large, the
      weight changes of a larger cohort of patients who underwent DBS for OCD or major
      depressive disorder (MDD) were studied. RESULTS: Data were available for 46
      patients (30 OCD and 16 MDD patients; mean age 46.2 years, SD 10.9) with an
      average baseline body mass index (BMI) of 28.0 (SD 7.3), 26 of whom (57%) were
      overweight (n = 11), obese (n = 12), or morbidly obese (n = 3). Mean follow-up
      was 3.8 years (range 10 months to 8.7 years, SD 2.3), after which the average BMI
      was 28.1 (SD 7.0), not significantly different from baseline. The average BMI of
      the 15 patients with (morbid) obesity at baseline decreased from 36.8 to 34.6
      (ns), while the average BMI of the 31 normal or "only" overweight patients at
      baseline increased from 23.8 to 25.0 (ns). CONCLUSION: There was no significant
      change in body weight on group level after DBS for either OCD or MDD.

PMID- 29017177
TI  - Patients with newly diagnosed rheumatoid arthritis are at increased risk of
      diabetes mellitus: an observational cohort study.
AB  - AIMS: To reveal the prevalence of Diabetes Mellitus (DM) in patients with newly
      diagnosed Rheumatoid Arthritis (RA) and evaluate the association between clinical
      characteristics of RA and DM as well as treatment response in newly diagnosed RA
      patients with DM. METHODS: Newly diagnosed, adult, RA patients, who were
      registered in Danish Danbio since 1st January 2010, were included. Patients'
      demographics, serology results including rheumatoid factor (RF), anti-cyclic
      citrullinated peptide antibody (anti-CCP) and antinuclear antibody (ANA) as well
      as disease activity score in 28 joints-C-reactive protein (DAS28-CRP) at the time
      of diagnosis and after 4 months (+/-1-2 months) of treatment initiation were
      extracted from Danbio Registry. To reveal the presence of DM, patients'
      electronic medical records were reviewed. The prevalence of DM in our patients
      was compared (using an age- and gender-matched analysis) with that expected from
      Danish population. RESULTS: of 439 included patients, 60.1% were female, mean of
      age 64.6+/-15.0 years and RA disease duration 2.6+/-1.7 years. Prevalence of DM
      was 57/439 (12.9%), herein type II DM 52 (91.2%) and type I DM 5 (8.8%). Except
      for two patients, diagnosis of DM was established prior to the diagnosis of RA.
      The prevalence of DM in newly diagnosed RA patients of all ages was significantly
      increased versus that expected from Danish population (RR=2.21, CI=1.40-3.42, P
      min 0.001). In addition, prevalence of DM was significantly increased with more
      than twice of the expected for RA patients aged 65-84. Both genders showed
      increased risk of DM after subgroup analysis. The presence of DM in RA patients
      was significantly associated with age (P min 0.001) and RA disease duration >=4
      years (P =0.05). We did not find any significant associations between presence of
      DM and gender, RF, anti-CCP as well as ANA. Additionally, presence of DM in the
      RA patients was not a negative predictor of treatment response measured by the
      European League Against Rheumatism (EULAR) response criteria and ?DAS28-CRP.
      CONCLUSION: Newly diagnosed RA patients are at higher risk of DM (13% versus 5.7%
      in Denmark), and a high index of suspicion must be kept.

PMID- 29017178
TI  - Cardiovascular disease risk and androgen deprivation therapy in patients with
      localised prostate cancer: a prospective cohort study.
AB  - BACKGROUND: As androgen deprivation therapy (ADT) is increasingly being used in
      men with localised prostate cancer, our goal was to examine the association
      between ADT and the risk of cardiovascular disease (CVD). METHODS: We conducted a
      prospective cohort study using records of a large health-care system in
      California. The study included men with newly diagnosed localised prostate cancer
      (1998-2008) who initially underwent active surveillance (N=7637) and were
      followed through 2010. We examined 10 individual CVD outcomes. Cox proportional
      hazard models incorporated time-varying treatment variables and controlled for
      race/ethnicity, age, and tumour characteristics, recurrence risk, CVD medication
      use, and CVD risk factors. RESULTS: Of the 7637 subjects, nearly 30% were exposed
      to ADT. In the multivariable analyses, ADT was associated with an increased risk
      of heart failure (adjusted HR=1.81, 95% CI 1.40-2.32) in men without preexisting
      CVD. Elevated risks of arrhythmia (adjusted HR=1.44, 95% CI 1.02-2.01), and
      conduction disorder (adjusted HR=3.11, 95% CI 1.22, 7.91) were only observed
      among patients with preexisting CVD. CONCLUSIONS: In men with clinically
      localised prostate cancer who were initially under active surveillance, ADT was
      associated with a greater risk of heart failure in men without any preexisting
      CVD. We also found an increased risk of arrhythmia and conduction disorder in men
      with preexisting CVD. This study provides the basis for identifying high-risk men
      treated with ADT who might benefit from regular cardiac monitoring and lifestyle
      modification recommendations.

PMID- 29017181
TI  - Vitamin E in the Preterm Infant: A Forgotten Cause of Hemolytic Anemia.
AB  - OBJECTIVE:  Vitamin E deficiency in premature infants has been associated with
      hemolytic anemia. Its incidence decreased after the supplementation of preterm
      formulas and parenteral nutrition with vitamin E. Despite this, some infants
      still develop hemolytic anemia and receive vitamin E. STUDY DESIGN: 
      Retrospective analysis of 70 infants admitted to a level IV intensive care unit
      and who developed hemolytic anemia and were treated with vitamin E. Infants were
      classified into two groups based on whether or not they responded to vitamin E
      therapy. Statistical methods included the use of descriptive statistics and
      marginal logistic regression models. RESULTS:  Low hematocrit and reticulocytosis
      before vitamin E administration were associated with adequate response to
      treatment. Thrombocytosis, iron treatment (duration and dose), gestational age,
      birth weight, and type of feedings were not. Infants who received a short
      duration of parenteral nutrition and were on oxygen responded to vitamin E
      therapy. Infants with a hematocrit <= 26% and reticulocyte of 36.1% were more
      likely to respond to vitamin E. CONCLUSION:  Although formulas and parenteral
      nutrition are supplemented with vitamin E; some preterm infants may still develop
      hemolytic anemia. Those with anemia, reticulocytosis, and oxygen requirement may
      benefit from additional vitamin E.

PMID- 29017182
TI  - Factors and Outcomes of Persistent Pulmonary Hypertension of the Newborn
      Associated with Acute Kidney Injury in Thai Neonates.
AB  - OBJECTIVE:  This study aims to determine the risk factors and outcome of
      persistent pulmonary hypertension of the newborn (PPHN)-associated acute kidney
      injury (AKI). STUDY DESIGN:  Infants diagnosed with PPHN at Hat Yai Hospital from
      January 2012 to December 2016 were retrospectively reviewed. RESULTS:  Of the 109
      included PPHN infants, 28.4% (31/109) died, and AKI was found in 28.4% following
      neonatal KDIGO classification. Of the 31, 19 who died (61.3%) reached stage 1, 3
      (9.7%) reached stage 2, and 9 (29.0%) reached stage 3. AKI (all stages combined)
      was significantly associated with increased mortality with an odds ratio (OR) of
      8.71 (95% confidence interval [CI], 3.37-22.49). Multivariate logistic regression
      analysis indicated that male gender (adjusted OR = 8.56; 95% CI = 0.84-85.09) and
      urine output of < 1 mL/kg/h in 12 hours of admission (adjusted OR = 15.57; 95% CI
      = 2.58-93.98) were the main factors associated with an increased risk for AKI,
      while birth by cesarean delivery was associated with reduced risk of AKI
      (adjusted OR = 0.10; 95% CI = 0.16-0.68). CONCLUSION:  The incidence of AKI in
      PPHN was high in this study, and this complication was also significantly
      associated with higher mortality. In PPHN neonates, AKI should be especially
      closely monitored in males and infants who have a urine output of < 1 mL/kg/h in
      the first 12 hours of admission.

PMID- 29017179
TI  - SGK1 inhibition induces autophagy-dependent apoptosis via the mTOR-Foxo3a
      pathway.
AB  - BACKGROUND: Although inhibition of SGK1 has been shown to delay cancer
      progression, the underlying mechanisms have not yet been elucidated. METHODS: We
      investigated the cellular responses to GSK650394 treatment and SGK1 silencing (or
      overexpression) in human prostate cancer (PCa) cell lines and PC3 xenografts by
      flow cytometry, western blotting, immunofluorescence, transmission electron
      microscopy and immunohistochemistry. RESULTS: In the present study, we
      demonstrated that SGK1 inhibition, mediated by either GSK650394 or SGK1 shRNA,
      induced G2/M arrest, apoptosis and autophagy. Furthermore, 3MA-mediated autophagy
      inhibition attenuated SGK1 inhibition-induced apoptosis, suggesting that
      induction of autophagy precedes apoptosis. Moreover, ectopic expression of SGK1
      significantly attenuated the GSK650394-induced effects. Suppression of mTOR and
      Foxo3a phosphorylation is critical for blockade of SGK1-induced autophagy and
      apoptosis, at least partially via pFoxo3a (S253)-LC3 and pFoxo3a (S253)-p27
      interactions. Dual inhibition of mTOR and SGK1 enhances autophagy activation and
      leads to synergistic cytocidal effects in PCa cells. CONCLUSIONS: In summary, our
      findings show that SGK1 inhibition exhibits significant antitumour effects
      against PCa in vitro and in vivo. This study uncovered a novel mechanism of SGK1
      inhibition in PCa, which is mediated, at least in part, by inducing autophagy
      dependent apoptosis via the mTOR-Foxo3a pathway.

PMID- 29017180
TI  - Targeting apoptosis in acute myeloid leukaemia.
AB  - Acute myeloid leukaemia (AML) is a molecularly and clinically heterogeneous
      disease, and its incidence is increasing as the populations in Western countries
      age. Despite major advances in understanding the genetic landscape of AML and its
      impact on the biology of the disease, standard therapy has not changed
      significantly in the last three decades. Allogeneic haematopoietic stem cell
      transplantation remains the best chance for cure, but can only be offered to a
      minority of younger fit patients. Molecularly targeted drugs aiming at restoring
      apoptosis in leukaemic cells have shown encouraging activity in early clinical
      trials and some of these drugs are currently being evaluated in randomised
      controlled trials. In this review, we discuss the current development of drugs
      designed to trigger cell death in AML.

PMID- 29017183
TI  - Ultrasonic Assessment of Cervical Heterogeneity for Prediction of Spontaneous
      Preterm Birth: A Feasibility Study.
AB  - BACKGROUND:  In a normal pregnancy, cervical collagen fibers remain organized in
      predictable patterns throughout most of the gestation. Cervical remodeling
      reflects a rearrangement of collagen fibers in which they become increasingly
      disordered and contribute to the pathogenesis of spontaneous preterm birth.
      Quantitative ultrasound analysis of cervical tissue echotexture may have the
      capacity to identify microstructural changes before the onset of cervical
      shortening. OBJECTIVE:  The primary objective of this study was to examine the
      utility of a novel quantitative sonographic marker, the cervical heterogeneity
      index (HI), which reflects the relative organization of cervical collagen fibers.
      Also, we aimed to determine an optimal HI cut-point to predict spontaneous
      preterm birth. STUDY DESIGN:  This retrospective cohort study employed a novel
      image-processing technique on transvaginal ultrasound images of the cervix in
      gestations between 14 and 28 completed weeks. The transvaginal sonography images
      were analyzed in MATLAB (MathWorks, Natick, MA) using a custom image-processing
      technique that assessed the relative heterogeneity of the cervical tissue.
      RESULTS:  A total of 151 subjects were included in the study. The mean HI in
      subjects who delivered preterm and at term was 8.28 +/- 3.73 and 12.35 +/- 5.80,
      respectively (p < 0.0001). Thus, decreased tissue heterogeneity was associated
      with preterm birth, and increased tissue heterogeneity was associated with
      delivery at term. In our study population, preterm birth was associated with a
      short cervix (<2.5 cm), history of preterm birth and lower HI, and our findings
      indicate that HI may improve prediction of preterm birth. CONCLUSION: 
      Quantitative ultrasound measurement of the cervical HI is a promising,
      noninvasive tool for early prediction of spontaneous preterm birth.

PMID- 29017185
TI  - Pruritic, Bizarre Tracks- A Vacation Souvenir.

PMID- 29017184
TI  - Clinical characteristics and outcome of 60 pediatric patients with malignant
      melanoma registered with the German Pediatric Rare Tumor Registry (STEP).
AB  - Background Malignant melanoma (MM) is a common malignancy in adults while it is
      rare in children. Thus, information on clinical behavior of pediatric MM is
      incomplete. Patients The German Pediatric Rare Tumor Registry (STEP) presents a
      prospective analysis of 60 childhood MM cases diagnosed between June 2006 and
      December 2014. Method Patients' ages ranged between 0 and 17 years at initial
      diagnosis (median age 9.6 years). Information on patient's and tumor
      characteristics was obtained by standardized documentation. Three-year overall
      survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier
      test. Results Follow-up ranged from 0 to 116 months with a median of 36.5 months,
      however, univariate analysis was performed for 46 cases with a follow-up > 3
      months, only. Cases with spitzoid histotype (40%) did not show a significantly
      different outcome compared to cases with non-spitzoid MM. Breslow thickness <=
      2.00 mm was identified in 30% of the cases and 18% were Clark level I to III.
      Adjuvant therapy was used in 45% of cases. OS at 3 years was 100%, EFS 95.2%.
      Conclusion We present a series of cases with a high number of spitzoid malignant
      melanoma and advanced pediatric melanoma, but surprisingly good overall survival
      rates. Spitzoid and non-spitzoid MM do not differ in clinical behavior and
      survival.

PMID- 29017186
TI  - ?

PMID- 29017187
TI  - [Acute unilateral progressive exophthalmus].

PMID- 29017188
TI  - Curcumin Protects Mitochondria and Cardiomyocytes from Oxidative Damage and
      Apoptosis Induced by Hemiscorpius Lepturus Venom.
AB  - The main aim of the current study was to determine cardio-toxicity mechanisms of
      H. lepturus and protective effect of curcumin against this toxin in rats, using
      isolated heart mitochondria and cardiomyocytes. Our findings indicated that H.
      lepturus venom caused significantly ((P<0.05) cytotoxicity and caspase 3
      activation in cardiomyocytes and mitochondrial dysfunction including increased
      mitochondrial ROS level, swelling in the mitochondria, decline in the
      mitochondria membrane potential (MMP), decrease in the cytochrome-c oxidase
      activity (complex IV), decrease ATP level and finally mitochondrial outer
      membrane (MOM) rupture in isolated mitochondria. Our results showed that the
      administration of curcumin efficiently decreased (P<0.05) cytotoxicity and
      caspase 3 activation, ROS formation, MMP collapse, mitochondrial swelling and
      mitochondrial outer membrane (MOM) rupture. Our findings suggest H. lepturus
      venom cusses a disruptive effect on mitochondrial respiratory chain, especially
      on complex II, and IV that predispose cardiomyocytes to ATP depletion and death
      signaling that could be protected with administration of curcumin.

PMID- 29017189
TI  - Curcumin Affects Adipose Tissue-Derived Mesenchymal Stem Cell Aging Through TERT
      Gene Expression.
AB  - Aging and losing cell survival is one of the main problems in cell therapy. Aging
      of Mesenchymal Stem Cells (MSCs) is associated with a rise in intracellular
      reactive oxygen species, decrease in telomerase reverse transcriptase (TERT)
      expression and finally eroded telomere ends. Given that the production of free
      radicals in the aging process is effective, the use of antioxidants can help in
      scavenging free radicals and prevent the aging of cells. The aim of this study is
      to evaluate the effects of curcumin on proliferation, aging and TERT expression
      of rat adipose tissue-derived stem cells (rADSC). rADSCs were isolated from
      inguinal rat adipose tissue and their viabilities were assessed by MTT after
      exposure to different concentrations of curcumin. Flow-cytometry was performed
      for investigating the cell surface markers. Adipogenic and osteogenic
      differentiation were carried out to evaluate the pluripotency of rADSCs.
      Telomerase expression and percentage of senescent cells were evaluated using real
      time PCR and senescence-associated beta-galactosidase activity, respectively. The
      results demonstrated significant proliferation of rADSCs after 48 h treatment
      with 1 and 5 uM curcumin. Additionally, these concentrations could significantly
      reduce the population doubling time and aging of rADSCs at different passages.
      The findings of SA-beta-gal staining showed that curcumin significantly decreased
      the number of senescent cells in the 5 and 7 cell passages. Moreover, expression
      levels of TERT increased in the presence of 1 and 5 uM curcumin than control
      group (P<0.001). As a conclusion, curcumin may be a good candidate to improve
      lifespan of rADSCs through promoting TERT gene expression.

PMID- 29017190
TI  - [Factors Influencing Chronic Back Pain in Care Workers Attending to The Elderly
      in Germany].
AB  - INTRODUCTION: The present study determined the lifetime prevalence of chronic
      back pain in care workers attending to the needs of elderly in Rhineland
      Palatinate facilities and identified potential influencing factors. METHODS: In a
      cross-sectional survey, 155 care workers in 5 institutions for the elderly care
      were interviewed with a written questionnaire. Questions from different
      standardised questionnaires were combined with our own questions. We complemented
      the examination with 2 standardized exercise tests. The data were analysed using
      descriptive and bivariate as well as binary logistic regression analysis.
      RESULTS: The nurses (83.8%) were female, and the average age was 41 years. The
      lifetime prevalence of chronic back pain in female care workers was 50.8%. In
      male elderly care workers this was 20.0%. As potential influencing factors for
      chronic back pain, a bad subjective state of health and a weak endurance of back
      muscles could be identified. CONCLUSION: The lifetime prevalence of chronic back
      pain was higher in the care workers taking care of the elderly than in the data
      of the general population. Discussed risk factors for back pain such as too many
      tasks not directly associated with caretaking, time pressure or too many elderly
      residents turned out as not significant. However, the subjective state of health
      and the endurance of back muscles were related to back pain. Prospective studies,
      which focus on physical and psychological stress, strain and resources, are
      needed to understand the causality of the high lifetime prevalence of chronic
      back pain in care workers in homes for the elderly better.

PMID- 29017191
TI  - [Burnout Prevention and Mobile Mindfulness: Evaluation of an App-Based Health
      Training Program for Employees].
AB  - OBJECTIVE: Mindfulness recently attracted growing interest beyond classical
      therapeutic contexts and has been adopted in preventive labor contexts and
      occupational health. In this study, we evaluated the effectiveness of a mobile
      mindfulness training app regarding work and health indicators. METHODS:
      Participants were employees and assigned randomly to the intervention and control
      groups. 146 employed participants in the intervention group used the mobile
      application '7mind' for 14 days. Comparisons were made with 160 employed
      participants from the control group, who were given access to the app after
      finishing the study (wait-list control). RESULTS: After two weeks of use,
      significant effects of the training were indicated by better results for the
      intervention group as compared to the control group. Some of the effect sizes can
      be considered as large: participants in the intervention group improved in
      measures of mindfulness, work engagement, job satisfaction, emotional exhaustion,
      emotional intelligence, innovation and creativity, and self-efficacy. CONCLUSION:
      Conventional mindfulness training programs are organized in groups. Our study
      demonstrates for the first time the effectiveness of a mobile mindfulness
      training app in the work context. The mobile app offers an easy and flexible
      access to training mindfulness and improving work and health-related indicators.

PMID- 29017192
TI  - [Horizon Scanning in Health Care: A German Perspective].
AB  - Background Decision makers in health care act in an area in which expectations
      increase to make beneficial new technologies available as soon as possible, to
      protect patients from unsafe or ineffective technologies, and to expedite or
      decelerate technology diffusion. Horizon Scanning (HS) is a process to identify
      early new and emerging technologies and to inform about their potential
      consequences concerning the health care system. Objectives Methods of HS,
      worldwide existing activities and the status quo in Germany are described.
      Methods In April 2015, a systematic electronic search was conducted which was
      supplemented by hand searching. Additionally, a qualitative acquisition of German
      expert knowledge in health care was realized. Results 27 formal HS systems (HSS)
      worldwide were identified of which 18 are current members of the "International
      Information Network on New and Emerging Health Technologies". Essentially, the
      same process steps are applied but there may be differences in methods due to
      different structures and interests of the health care systems. There is no
      official HSS in Germany. The survey of experts revealed a lack of knowledge and a
      varying understanding of HS, but basically there seems to be a need for this.
      Conclusions The systematic process of HS can be adapted to current circumstances
      and objectives of a specific health care system and has international acceptance.
      In Germany, it could enable decision makers and other stakeholders to have
      information early and thus support them in their decisions.

PMID- 29017193
TI  - [The Environmental Burden of Disease Concept].
AB  - GOAL OF THE STUDY: Environmental risk factors are of great importance for public
      health with a considerable but often unused potential for prevention. However,
      knowledge about the complex associations between the environment and health
      effects is limited for some risk factors. A concept, which is using the existing
      evidence on associations between the impact of environmental factors and health
      effects, is the environmental burden of disease (EBD) concept. The aim of this
      article is to present the quantification method of the EBD concept and to discuss
      the advantages and its points of criticism. METHODS: The EBD concept combines
      morbidity and mortality data in a single measure (Disability-Adjusted Life Year,
      DALY) to enable a comparative description of the burden of disease. Life years
      are used as measurement unit. The environmental share of the total DALYs is
      quantified by using the attributable fraction. RESULTS: Despite its increasing
      application especially in the international context, the method is still
      criticized, because by summarizing the complex construct of health in one single
      measurement unit, much important information about quality of life is lost. A
      further criticism refers to partly arbitrarily set social value choices.
      Additionally, missing or insufficient data can limit the quality and validity of
      EBD estimations. CONCLUSION: A scientific discourse is needed to decide to what
      extent the EBD approach can and should be used in Germany.

PMID- 29017194
TI  - Non-operative Management for Uncomplicated Appendicitis: An Option to Consider.
AB  - AIM:  The main goal of our study was to assess a 7 days long course of
      antibiotics for acute uncomplicated appendicitis. MATERIALS AND METHODS:  From
      March 2014 to November 2015, all patients diagnosed with acute appendicitis have
      been considered to be treated by only antibiotics. Inclusion criteria included
      clinical (tenderness), biological (C-reactive protein [CRP] < 50), and
      radiological features (diameter > 6 mm). All patients were treated with
      intravenous amoxicillin and clavulanic acid (100 mg/kg/day) for 2 days (six
      doses). At the end of the treatment, clinical and paraclinical examinations
      included blood samples at day 7 and ultrasound (US) scan at 3 months. RESULTS:  A
      total of 166 patients were treated and followed up prospectively during the study
      period. Mean age at diagnosis was 10.8 +/- 0.6 years. All children, but four were
      discharged with a clinical improvement after 48 hours and six intravenous
      antibiotics injection according to our protocol. Four children required surgery
      during the initial hospitalization period.Initial ultrasound scan showed a mean
      diameter of 7.85 +/- 1.6 mm, with inflamed fat in 124 patients (74.7%). At Day 7,
      the diameter was 5.2 +/- 1.6 mm (p < 0.0001).During a median follow-up of 18.8
      months (3.5-18), 22 patients (13.25%) had to be managed for a novel episode of
      acute appendicitis after a median period of 138 days (13-270). None had to be
      managed for a complicated appendicitis. CONCLUSION:  Non-operative treatment
      (NOT) is a safe alternative for the management of uncomplicated acute
      appendicitis in children. Further study should be conducted to determine relapse
      risk factors.

PMID- 29017195
TI  - [Old and new reflexes - and the personality of ALS patients].

PMID- 29017196
TI  - [The role of eye movement desensitization and reprocessing (EMDR) in substance
      use disorders: A systematic review].
AB  - Eye Movement Desensitization and Reprocessing (EMDR) is a therapeutic method that
      has been shown to be especially effective in traumatic disorders. Since the
      concept of an addiction memory has become widely accepted, the use of EMDR also
      in substance use disorders (SUD) treatment might count as a separate field. This
      review summarizes the current state of research on treatment effects EMDR in SUD.
      The literature search included the databases of PubMed and PsychInfo; four
      studies met the inclusion criteria. EMDR was found to be related to a decreased
      amount of craving, fear and depression and to an improvement of emotion
      regulation and management and self-esteem. Initial findings indicate a high
      therapeutic potential of EMDR in SUD treatment.

PMID- 29017197
TI  - [500 Years of Reformation: The History of Martin Luther's Pathography and its
      Ethical Implications].
AB  - Introduction In the context of the 500th anniversary of the Reformation, it is
      time to take a survey of the history of Martin Luther's (1483-1546) pathography
      and to deduce possible conclusions from it for psychiatric practice. Results In a
      1035-page work written in German between 1937 and 1941, the Dane Paul Reiter
      retrospectively diagnosed Luther as manic-depressive. In 1956, Grossmann was
      unable to prove persistent synchronicity of depressive mood and reduced
      motivation in Luther in the key years 1527 and 1528, which led him to conclude
      that Luther had a cyclothymic personality with a pyknic constitution. Discussion
      One very central source of Luther's life's work may have arisen from the tension
      between emotional constraints and crises of faith, on the one hand, and
      resilience and trust in God, on the other. Conclusion Luther can be used as an
      example of the importance of religiousness as a curative resource for the psyche.

PMID- 29017198
TI  - Aggressive treatment of cerebral venous sinus thrombosis (CVT) with stent
      retrievers and local thrombolysis: why we need a registry.
AB  - Purpose Anticoagulation is the first-line therapy for cerebral venous sinus
      thrombosis (CVT). Endovascular treatment is increasingly applied in patients
      deteriorating despite anticoagulation with extensive thrombosis or
      contraindications for anticoagulation. Experience with stent retrievers in CVT is
      limited. Results We present three cases of severe CVT treated with stent
      retrievers, thrombus aspiration and local thrombolysis. In two patients with
      extensive thrombosis, a partial recanalization was achieved, but only one of them
      showed significant improvement. Despite failed recanalization, the third patient
      recovered completely. Conclusions Limited experience with three cases indicates
      that recanalization may not necessarily result in favourable clinical outcome
      even in severely affected patients. Therefore, invasive procedures such as local
      thrombolysis and thrombectomy remain individual therapeutic options when
      anticoagulation fails and in patients with extensive thrombosis.

PMID- 29017199
TI  - [Ciguatera or why you should enquire about fish consumption in cases of cold
      allodynia].
AB  - Ciguatoxine sind potente, von Mikroalgen produzierte, marine Biotoxine, die sich
      in tropischen Raubfischen, lokal und saisonal unterschiedlich stark, anreichern
      konnen. Kurze Zeit nach dem Fischverzehr treten gastrointestinale, neurologische
      und/oder kardiovaskulare Vergiftungssymptome auf. Durch die hohe Affinitat der
      Toxine zu neuronalen Natriumkanalen sind neurologische Symptome fur Ciguatera
      Vergiftungen charakteristisch. Nahezu pathognomonisch ist dabei die
      Kalteallodynie, bei der kalte Oberflachen als heibeta, schmerzhaft oder extrem
      unangenehm empfunden werden. Durch Importe von Tropenfisch tritt Ciguatera
      zunehmend auch in gemabetaigten Klimazonen auf. Wir erlautern anhand zweier Falle
      die Besonderheiten dieser Fischvergiftung.

PMID- 29017200
TI  - [Not Available].

PMID- 29017202
TI  - [Centers in Health Care: whereto?]

PMID- 29017203
TI  - [Not Available].

PMID- 29017204
TI  - [Not Available].

PMID- 29017205
TI  - [Not Available].

PMID- 29017206
TI  - [Not Available].

PMID- 29017207
TI  - [Not Available].

PMID- 29017208
TI  - [Not Available].

PMID- 29017209
TI  - [Not Available].

PMID- 29017210
TI  - [Not Available].

PMID- 29017211
TI  - [Not Available].

PMID- 29017212
TI  - [Not Available].

PMID- 29017213
TI  - [Not Available].

PMID- 29017214
TI  - [51-year-old man with with acute coronary syndrome and bipulmonary infiltrates].

PMID- 29017216
TI  - Erratum for: DNA Barcoding for Industrial Quality Assurance.

PMID- 29017215
TI  - [Pulmonary Embolism Despite Rivaroxaban in an Obese Patient].
AB  - Introduction Rivaroxaban, an oral factor Xa inhibitor, is approved for therapy of
      venous thromboembolism. It is unclear whether the standard dose for patients with
      a body mass index (BMI) > 40 kg/m2 is sufficient. History The 45-year-old patient
      was admitted because of increasing respiratory distress. She had a history of
      pulmonary embolism 30 months before the admission, a factor V Leiden mutation and
      several hospitalisations due to dermatomycoses. The patient briefly took
      phenprocoumon which was changed to 20 mg rivaroxaban due to a lack of adherence.
      Six months before admission, the patient paused the rivaroxaban therapy because
      of dental surgery and suffered a recurrent pulmonary embolism. Findings and
      Diagnosis The patient presented with increasing difficulty of breathing, morbid
      obesity with a BMI of 59.3 kg/m2 and intertrigo of the lower extremities. The ECG
      showed a right axis deviation, a pulmonary P-wave and an incomplete right bundle
      branch block. Computed tomography showed pulmonary embolisms of the left lower
      lobe. The pulmonary artery was dilated, and the right atrium was enlarged. Venous
      thrombosis of the lower limb could not be certainly ruled out. The D-dimer was
      elevated with 5.895 mg/L (normal value up to 169 mg/L) and NT-pro-BNP was
      elevated at 5.580 ng/L (normal value up to 0.5 ng/L). Sixteen hours after the
      onset of symptoms, 22 hours after the last dose, the serum rivaroxaban level was
      137 ng/ml. According to manufacturers, the therapeutic range of rivaroxaban after
      2 - 4 hours is 22 - 535 ng/ml, and after 24 hours 6 - 239 ng/ml. Therapy and
      course After initiation of a therapy with low-molecular weight heparin and
      subsequent oral anticoagulation with phenprocoumon, the symptoms decreased.
      Conclusions It is highly probable that the pulmonary embolism occurred at a time
      when the rivaroxaban level was in the therapeutic range. Since there are only few
      data about safety and efficacy of rivaroxaban and other non-vitamin K-oral
      anticoagulants (NOACs) in severely obese patients, the recommendations of the
      "International Society for Thrombosis and Haemostasis" should be followed:
      Rivaroxaban and other NOACs should not be used in patients with a BMI > 40 kg/m2
      or weight > 120 kg, since only few data on this patient group are available. If
      NOACs are necessary in these patients, serum concentrations of NOACs should be
      measured.

PMID- 29017217
TI  - 5,4'-Dihydroxy-7,8-dimethoxyflavanone and Aliarin from Dodonaea viscosa Are
      Activators of PPARgamma.
AB  - PPARgamma agonists are widely used medications in diabetes mellitus therapy.
      Their role in improving adipose tissue function contributes to antidiabetic
      effects. The extracts of Dodonaea viscosa have been reported to exert
      antidiabetic activity. However, the effective mediators and the underlying
      mechanisms were largely unknown. In this study, we investigated the action on
      PPARgamma transactivation and adipocyte modulation of two typical flavonoid
      constituents from D. viscosa, 5,4'-dihydroxy-7,8-dimethoxyflavanone and aliarin.
      Our results showed that 5,4'-dihydroxy-7,8-dimethoxyflavanone and aliarin were
      potential partial PPARgamma agonists. The compounds induced adipogenesis in 3T3
      L1 cells, with an upregulated adiponectin mRNA level and enhanced insulin
      sensitivity. The favorable effects of 5,4'-dihydroxy-7,8-dimethoxyflavanone,
      aliarin, and other flavonoid constituents on adipocytes might contribute to the
      antidiabetic efficacy of D. viscosa.

PMID- 29017218
TI  - Patient Factors Associated with Failure of Flap Coverage Used during Revision
      Total Knee Arthroplasty.
AB  - Revision total knee arthroplasty (rTKA) is a challenging problem in the setting
      of soft tissue defects. The purpose of this study was to evaluate patients who
      underwent rTKA requiring flap coverage and determine patient factors that
      predisposed them to failure. Forty-three consecutive patients (mean follow-up,
      46.5 months) who underwent rTKA requiring flap coverage were retrospectively
      reviewed between January 1, 2000 and December 31, 2010. Sixteen of 43 patients
      experienced failure requiring either flap revision (n = 2) or above the knee
      amputation (n = 14). Patients with heart failure (p = 0.008), cancer (p = 0.049),
      or infection with Klebsiella pneumoniae (p = 0.002) had greater rates of failure.
      Smoking (p = 0.287), diabetes (p = 0.631), and flap type (p = 0.634, p = 0.801)
      were not associated with increased failure. Mean survival was 46.4 months.
      Survival of patients with a history of cancer (34.3 months) was less (p = 0.033)
      than those without (49.2 months). Flap coverage in rTKA is a viable limb salvage
      option for patients with soft tissue defects; however, failure rates are much
      higher than in patients not requiring flap coverage.

PMID- 29017220
TI  - [Bronchitis Plastica - Acute Dyspnea and Branching Airway Casts].
AB  - : A 65 year old female presented to the emergency department with dyspnea and
      progressive cough with very viscous elongated secretion plugs. She suffered from
      multiple cardiac comorbidities and chronic heart failure. The CT scan of the
      thorax demonstrated extensive pulmonary infiltrates, unspecific mediastinal
      lymphadenopathy and enlargement of pulmonary lymph vessels. Bronchoscopy was
      performed and showed extensive occlusive bronchial casts. We diagnosed a case of
      bronchitis plastica. Therapy with inhalative heparin led to clinical improvement.
      CONCLUSION: bronchitis plastica is a rare disease with formation of occlusive
      bronchial casts. They are often found in cardiac disease or lymphatic disease.

PMID- 29017222
TI  - [Editor's Comment].

PMID- 29017223
TI  - ?

PMID- 29017221
TI  - [Biologicals in the Treatment of Bronchial Asthma].
AB  - Biologicals are a therapeutic option for patients with severe asthma. Difficult
      asthma in patients with untreated comorbidities or persistent trigger factors is
      much more common than severe refractory asthma. Optimized medical treatment,
      adherence to medication, elimination of trigger factors and treatment of
      comorbidities are essential before escalating the therapy with a biological. A
      careful phenotyping of patient with severe asthma is necessary because all
      available biological are only effective in certain phenotypes of the disease. For
      patients with severe allergic asthma an antibody against IgE (Omalizumab) is
      available. For patients with severe asthma and eosinophilic inflammation the
      Interleukin (IL)-5 Antibodies Mepolizumab and Reslizumab have recently been
      approved. The most prominent effect of biological treatment is the reduction of
      acute exacerbations in these patients. Further antibodies against IL-5 receptor
      (Benralizumab) or against the IL-4 receptor alpha chain (Dupilumab) are in
      advanced clinical development.

PMID- 29017219
TI  - [Consensus-Based Guidelines for Diagnosis, Prevention and Treatment of
      Tuberculosis in Children and Adolescents - A Guideline on Behalf of the German
      Society for Pediatric Infectious Diseases (DGPI)].
AB  - Recently, epidemiological data shows an increase of childhood tuberculosis in
      Germany. In addition to this, drug resistant tuberculosis becomes more frequent.
      Therefore, diagnosis, prevention and therapy in childhood and adolescence remain
      a challenge. Adult guidelines do not work for children, as there are age specific
      differences in manifestation, risk of progression and diagnostic as well as
      therapeutic pathways.The German Society for Pediatric Infectious Diseases (DGPI)
      has initiated a consensus-based (S2k) process and completed a paediatric
      guideline in order to improve and standardize care for children and adolescents
      with tuberculosis exposure, infection or disease.Updated dosage recommendations
      take age dependant pharmacokinetics in the treatment of drug sensitive but also
      drug resistant tuberculosis in account. In addition to this, there is a detailed
      chapter on perinatal exposure and disease as well as extrapulmonary
      manifestations.

PMID- 29017225
TI  - ?

PMID- 29017224
TI  - ?

PMID- 29017226
TI  - ?

PMID- 29017227
TI  - ?

PMID- 29017228
TI  - ?

PMID- 29017229
TI  - [A new positioning maneuver for treating a subtype of postural unsteadiness -
      based on a modified model of the utricular macula].
AB  - Objectives: A new method for the treatment of a subtype of postural unsteadiness
      frequently seen in the medical office is proposed. Ten years of successful
      practical application and continuous refining of this new treatment lead to the
      definition of symptom-criteria, which are useful to distinguish patients, who get
      benefit by this new procedure and to a modified model of the utricular macula.
      Materials and Methods: In a retrospective collection, the data of 15 patients
      with postural unsteadiness (mean duration of symptoms 61.7 months) successfully
      treated with the new maneuver are reported.Before treatment, all patients showed
      normal results in testing the caloric responses of the labyrinth, normal
      neurological investigation and no signs for cervical vertigo.Before and after
      treatment the DHI-score (Dizziness Handicap Index) was achieved by using the
      German version of the DHI-questionnaire. In all groups before and after treatment
      balance testing was performed using a posturography platform. Results:
      Application of the new treatment lead to a significant improvement of the DHI
      scores and of the posturographic results (significant reduction of body sway).
      Discussion: The patients, who were successfully treated by the new maneuver have
      had presented the same symptoms like patients with a proven utricular
      dysfunction. This leads to a slightly modified model of the utricular macula.
      Beyond correctly positioned otoconia in the utricular macula and free otoconia in
      the endolymphatic utricular space, a third fraction of dysfunctional partially
      detached otoconia is postulated (causing the unsteadiness). Based on this theory,
      the single hair-cell with its accompanied otoconium might be the smallest
      receptor-unit of the macula-organ. This smallest receptor-unit might represent a
      biological mass-spring-system. According to technical mass-spring-systems used as
      accelerometers, the different sizes of the otoconia for a distinct direction of
      acceleration are necessary for covering different frequency-bands.Finally, a many
      years successfully tested modified variation of the new maneuver for treatment in
      the medical office and for self-treatment is proposed.

PMID- 29017230
TI  - [Guidelines in Practice: The New S3 Guideline "Sleeping Disorders - Sleep-Related
      Abnormal Breathing"].
AB  - Sleep related breathing disorders include central sleep apnea (CSA), obstructive
      sleep apnea (OSA), sleep-related hypoventilation, and sleep-related hypoxia.
      These disorders are frequent and growing in clinical relevance. The related
      chapter of the S3 guideline "Non-restorative sleep/Sleep disorders", published by
      the German Sleep Society (DGSM), has recently been updated in November 2016.
      Epidemiology, diagnostics, therapeutic procedures, and classification of sleep
      related disorders have been revised. Concerning epidemiology, a considerably
      higher mortality rate among pregnant women with OSA has been emphasized. With
      regards to diagnostics, the authors point out that respiratory polygraphy may be
      sufficient in diagnosing OSA, if a typical clinical condition is given. For CSA,
      recommendations were changed to diagnose CSA with low apnea rates present.
      Significant changes for treating CSA in patients with left ventricular
      dysfunction have been introduced. In addition, there is now to be differentiated
      between sleep-related hypoventilation and sleep-related hypoxaemia. Obesity
      hypoventilation syndrome is discussed in more detail. This article sums up and
      comments on the published changes.

PMID- 29017231
TI  - [Long-term Follow up and patient satisfaction after tympanoplasty with Titanium
      Clip-Prothesis].
AB  - Aim of the present study is to evaluate the long term results of ossiculoplasty
      using titanium clip prosthesis. A retrospective analysis with prospective follow
      up has been done including for all patients who had a Clip-PORP implanted between
      the years 2002-2013. Following this, audiometric hearing results were measured
      with clinical examination including otoscopy and quality of life evaluation using
      Glasgow benefit inventory. 48 patients (51 ears, 29 men, 19 women, average age
      44.1 years) received followed up after an average duration of 6.3 years. The
      overall air-bone-gap (0.5-4 kHz) decreased from 22.8 dB preoperatively to 14.6 dB
      postoperatively (p<=0.001). The most frequent indication for surgical treatment
      were cholesteatomas and recurrent cholesteatomas (52%), chronic inflammation of
      middle ear (12%), revision of radical mastoidectomy (8%) and disturbance in sound
      conduction after previous operation (14%). Tympanic membrane was closed in 47
      times (92,2%), 4 times (7,8%) there was a defect. Clip-PORP was in situ 39 times
      (75%), protrusion and disposal were detected 6 times (11,8%) and 2 times (4%),
      respectively. However, 1 time (2%) the prothesis was lost or evaluation was not
      possible (3 times, 5,9%). The overall patient satisfaction and general subscale
      score after the treatment was beneficially evaluated. There was no change in
      social support score nore the physical health score. In summary, the ossicular
      chain reconstruction using titan Clip-PORP is safe and well established. Also in
      long-term analysis stable hearing results due to reduction of air bone gap are
      represented. The subjective quality of life is sustainable improved.

PMID- 29017232
TI  - ?

PMID- 29017233
TI  - [Not Available].

PMID- 29017234
TI  - ?

PMID- 29017235
TI  - ?

PMID- 29017236
TI  - Host Innate Immunity against Hepatitis E Virus and Viral Evasion Mechanisms.
AB  - Hepatitis E virus (HEV) infections cause epidemic or sporadic acute hepatitis,
      which are mostly self-limiting. However, viral infection in immunocompromised
      patients and pregnant women may result in serious consequences, such as chronic
      hepatitis and liver damage, mortality of the latter of which reaches up to 20
      30%. Type I interferon (IFN)-induced antiviral immunity is known to be the first
      line defense against virus infection. Upon HEV infection in the cell, the virus
      genome is recognized by pathogen recognition receptors, leading to rapid
      activation of intracellular signaling cascades. Expression of type I IFN triggers
      induction of a barrage of IFN-stimulated genes, helping the cells cope with viral
      infection. Interestingly, some of the HEV-encoded genes seem to be involved in
      disrupting signaling cascades for antiviral immune responses, and thus crippling
      cytokine/chemokine production. Antagonistic mechanisms of type I IFN responses by
      HEV have only recently begun to emerge, and in this review, we summarize known
      HEV evasion strategies and compare them with those of other hepatitis viruses.

PMID- 29017237
TI  - Biochemical Characterization of a Psychrophilic Phytase from an Artificially
      Cultivable Morel Morchella importuna.
AB  - Psychrophilic phytases suitable for aquaculture are rare. In this study, a
      phytase of the histidine acid phosphatase (HAP) family was identified in
      Morchella importuna, a psychrophilic mushroom. The phytase showed 38% identity
      with Aspergillus niger PhyB, which was the closest hit. The M. importuna phytase
      was overexpressed in Pichia pastoris, purified, and characterized. The phytase
      had an optimum temperature at 25 degrees C, which is the lowest among all the
      known phytases to our best knowledge. The optimum pH (6.5) is higher than most of
      the known HAP phytases, which is fit for the weak acidic condition in fish gut.
      At the optimum pH and temperature, MiPhyA showed the maximum activity level
      (2,384.6 +/- 90.4 MUmol.min-1.mg-1, suggesting that the enzyme possesses a higher
      activity level over many known phytases at low temperatures. The phytate
      degrading efficacy was tested on three common feed materials (soybean
      meal/rapeseed meal/corn meal) and was compared with the well-known phytases of
      Escherichia coli and A. niger. When using the same amount of activity units,
      MiPhyA could yield at least 3* more inorganic phosphate than the two reference
      phytases. When using the same weight of protein, MiPhyA could yield at least 5*
      more inorganic phosphate than the other two. Since it could degrade phytate in
      feed materials efficiently under low temperature and weak acidic conditions,
      which are common for aquacultural application, MiPhyA might be a promising
      candidate as a feed additive enzyme.

PMID- 29017238
TI  - Correlation between Changes in Microbial/Physicochemical Properties and
      Persistence of Human Norovirus during Cabbage Kimchi Fermentation.
AB  - Recently, cabbage kimchi has occasionally been associated with the foodborne
      diseases of enteric viruses such as human norovirus (HuNoV). This study aimed to
      evaluate the correlation between microbial/physicochemical properties and
      persistence of HuNoV in experimentally contaminated cabbage kimchi fermented and
      stored at 4 degrees C or 10 degrees C for 28 days. Changes in organic acid
      content, lactic acid bacteria (LAB), acidity, pH, and salinity were analyzed. The
      recovery of structurally intact HuNoV was examined for up to 28 days post
      inoculation, using a NoV GII.4 monoclonal antibody-conjugated immuno-magnetic
      separation method combined with quantitative real-time reverse transcription
      polymerase chain reaction. On day 0, LAB loads were 4.70 log10 colony forming
      units/g and HuNoV GII.4 titers were 2.57 log10 genomic copies/MUl, at both
      temperatures. After 28 days, intact HuNoV titers decreased to 1.58 (4 degrees C)
      and 1.04 (10 degrees C) log10 genomic copies/MUl, whereas the LAB density
      increased. This correlated with a gradual increase in lactic acid and acetic acid
      at both temperatures. Our findings support a statistical correlation between
      changes in physicochemical properties and the recovery of structurally intact
      HuNoV GII.4. Moreover, we determined that the production of organic acid and low
      pH could affect HuNoV GII.4 titers in cabbage kimchi during fermentation.
      However, HuNoV GII.4 was not completely eliminated by microbial/physicochemical
      factors during fermentation, although HuNoV GII.4 was reduced. Based on this, we
      speculate that the persistence of HuNoV GII.4 may be affected by the continually
      changing conditions during kimchi fermentation.

PMID- 29017239
TI  - Introduction to Special Section: Pediatric Psychology and Child Unintentional
      Injury Prevention: Current State and Future Directions for the Field.

PMID- 29017240
TI  - Pull Incentives for Antibacterial Drug Development: An Analysis by the
      Transatlantic Task Force on Antimicrobial Resistance.
AB  - New alternative market models are needed to incentivize companies to invest in
      developing new antibacterial drugs. In a previous publication, the Transatlantic
      Task Force on Antimicrobial Resistance (TATFAR) summarized the key areas of
      consensus for economic incentives for antibacterial drug development. That work
      determined that there was substantial agreement on the need for a mixture of push
      and pull incentives and particularly those that served to delink the revenues
      from the volumes sold. Pull incentives reward successful development by
      increasing or ensuring future revenue. Several pull incentives have been proposed
      that could substantially reward the development of new antibacterial drugs. In
      this second article authored by representatives of TATFAR, we examine the
      advantages and disadvantages of different pull incentives for antibacterial drug
      development. It is TATFAR's hope that this analysis, combined with other related
      analyses, will provide actionable information that will shape policy makers'
      thinking on this important issue.

PMID- 29017241
TI  - Vancomycin Minimum Inhibitory Concentration Is Not a Substitute for Clinical
      Judgment: Response to Healthcare-Associated Ventriculitis and Meningitis.

PMID- 29017242
TI  - High-Dose Daptomycin and Mortality: The Case Is Not Yet Closed.

PMID- 29017243
TI  - Reply to Chanderraj et al.

PMID- 29017244
TI  - Plasma Indoleamine 2, 3-Dioxygenase, a Biomarker for Tuberculosis in Human
      Immunodeficiency Virus-Infected Patients.
AB  - Background: There is no biomarker for diagnosing active tuberculosis in patients
      with human immunodeficiency virus (HIV) infection. Indoleamine 2, 3-dioxygenase
      (IDO) is an immunoregulatory enzyme that breaks down tryptophan (Trp) to
      metabolites known as kynurenines (Kyns). We investigated whether IDO activity, as
      measured by the ratio of Kyn to Trp, could be used to diagnose or predict active
      tuberculosis disease in HIV-infected adults. Methods: Kyn and Trp concentrations
      were measured using ultraperformance liquid chromatography mass spectrometry in
      plasma samples from 32 HIV-infected patients in whom active tuberculosis
      developed and who were followed up prospectively. We compared to 70 HIV-infected
      control subjects from the same cohort in whom tuberculosis did not develop,
      matched by age, sex, and CD4 cell count, and 37 unmatched HIV-infected patients
      with a diagnosis of pneumonia. Clinical parameters, including body mass index,
      CD4 cell count, HIV load, and C-reactive protein levels were analyzed. Results:
      At the time of tuberculosis diagnosis, IDO activity was significantly higher in
      patients with tuberculosis than in controls (P < .001). Six months before
      tuberculosis diagnosis, IDO activity was significantly higher in all patients who
      later developed tuberculosis (P < .001) than controls. After 6 months of
      tuberculosis treatment, IDO activity in patients with tuberculosis declined to
      levels similar to those in controls. IDO activity was 4-fold higher in patients
      with tuberculosis than in those with pneumonia, and could be used to distinguish
      them. With a receiver operating characteristic curve, IDO activity had a
      sensitivity of 97%, a specificity of 99%, and positive and negative predictive
      values of 89% and 100% for detecting active tuberculosis disease. Conclusion:
      Plasma IDO activity is suitable as a biomarker of active tuberculosis in HIV
      positive patients.

PMID- 29017245
TI  - A Community Perspective on the Inclusion of Pregnant Women in Tuberculosis Drug
      Trials.
AB  - Affecting both mother and the existing pregnancy, tuberculosis (TB) increases the
      likelihood of poor birth outcomes. Despite substantial clinical need for TB
      prevention and treatment, pregnant women remain neglected by research
      initiatives. As members of 3 community advisory boards that provide input into TB
      drug trials, we offer a community perspective on the inclusion of pregnant women
      in TB drug research and discuss (1) our perspective on the risk/benefit tradeoff
      of including pregnant women in research to address different forms of TB; (2)
      recent examples of progress in this area; (3) lessons learned from the human
      immunodeficiency virus research field, where pregnant women have enjoyed better
      although imperfect-representation in research; and (4) recommendations for
      different stakeholders, including researchers, regulatory authorities, ethics
      committees, and policymakers.

PMID- 29017246
TI  - Viral Load and Cytokine Response Profile Does Not Support Antibody-Dependent
      Enhancement in Dengue-Primed Zika Virus-Infected Patients.
AB  - Background: The pathogenesis of severe dengue disease involves immune components
      as biomarkers. The mechanism by which some dengue virus (DENV)-infected
      individuals progress to severe disease is poorly understood. Most studies on the
      pathogenesis of severe dengue disease focus on the process of antibody-dependent
      enhancement (ADE) as a primary risk factor. With the circulation of Zika virus
      (ZIKV) in DENV-endemic areas, many people infected by ZIKV were likely exposed to
      DENV. The influence of such exposure on Zika disease outcomes remains unknown.
      Methods: We investigated whether patients previously exposed to DENV exhibited
      higher viremia when exposed to a subsequent, heterologous dengue or Zika
      infection than those patients not previously exposed to dengue. We measured viral
      loads and cytokine profile during patients' acute infections. Results: Neither
      dengue nor Zika viremia was higher in patients with prior DENV infection,
      although the power to detect such a difference was only adequate in the ZIKV
      analysis. Of the 10 cytokines measured, only 1 significant difference was
      detected: Levels of interleukin 1beta (IL-1beta) were lower in dengue-infected
      patients who had experienced a previous dengue infection than patients infected
      with dengue for the first time. However, power to detect differences between
      groups was low. In Zika-infected patients, levels of IL-1beta showed a
      significant, positive correlation with viral load. Conclusions: No signs of ADE
      were observed in vivo in patients with acute ZIKV infection who had prior
      exposure to DENV.

PMID- 29017247
TI  - A 17-Year Nationwide Study of Burkholderia cepacia Complex Bloodstream Infections
      Among Patients in the United States Veterans Health Administration.
AB  - Background: Burkholderia cepacia complex (Bcc) are a group of multidrug-resistant
      gram-negative bacteria rarely reported in patients without cystic fibrosis (CF)
      or immunocompromising conditions. We investigated Bcc bloodstream infections
      (BSIs) in a cohort of non-CF patients from the US Veterans Health Administration
      (VHA). Methods: Using VHA databases, we identified patients with Bcc BSI at
      facilities nationwide from 1999 through 2015. We ascertained clinical
      characteristics, treatments, and outcomes and identified factors associated with
      30-day mortality in logistic regression analysis. Results: We identified 248
      patients with Bcc BSI, who were of advanced age (mean, 68 years), chronically
      ill, and had severe disease. The most common sources were central venous
      catheters (41%) and pneumonia (20%). Most cases were hospital-acquired (155
      [62%]) or healthcare-associated (70 [28%]). Mortality at 14, 30, and 90 days was
      16%, 25%, and 36%, respectively. Trimethoprim-sulfamethoxazole (TMP-SMX) and
      fluoroquinolones were active against 94% and 88% of isolates, respectively.
      Susceptibility to ceftazidime and meropenem occurred in approximately 70% of the
      isolates. The most prescribed antibiotics were fluoroquinolones (35%), followed
      by carbapenems (20%), TMP-SMX (18.5%), and ceftazidime (11%). In regression
      analysis, age (OR, 1.06 [95% confidence interval {CI}, 1.02-1.10], per added
      year) and the Pitt bacteremia score (OR, 1.65 [95% CI, 1.44-1.94], per unit
      increase) were associated with higher 30-day mortality. Conclusions: In this
      large cohort of BSIs caused by Bcc, cases were mostly hospital-acquired and we
      observed high mortality, significant resistance to ceftazidime, and limited use
      of TMP-SMX. These observations add to our understanding of Bcc infection in non
      CF patients and highlight the need for interventions to improve their outcome.

PMID- 29017248
TI  - Fluoroquinolone Resistance Mutation Detection Is Equivalent to Culture-Based Drug
      Sensitivity Testing for Predicting Multidrug-Resistant Tuberculosis Treatment
      Outcome: A Retrospective Cohort Study.
AB  - Background: Molecular diagnostics that rapidly and accurately predict
      fluoroquinolone (FQ) resistance promise to improve treatment outcomes for
      individuals with multidrug-resistant (MDR) tuberculosis (TB). Mutations in the
      gyr genes, though, can cause variable levels of in vitro FQ resistance, and some
      in vitro resistance remains unexplained by gyr mutations alone, but the
      implications of these discrepancies for treatment outcome are unknown. Methods:
      We performed a retrospective cohort study of 172 subjects with MDR/extensively
      drug-resistant TB subjects and sequenced the full gyrA and gyrB open reading
      frames in their respective sputum TB isolates. The gyr mutations were classified
      into 2 categories: a set of mutations that encode high-level FQ resistance and a
      second set that encodes intermediate resistance levels. We constructed a Cox
      proportional model to assess the effect of the gyr mutation type on the time to
      death or treatment failure and compared this with in vitro FQ resistance,
      controlling for host and treatment factors. Results: Controlling for other host
      and treatment factors and compared with patients with isolates without gyr
      resistance mutations, "high-level" gyr mutations significantly predict poor
      treatment outcomes with a hazard ratio of 2.6 (1.2-5.6). We observed a hazard of
      death and treatment failure with "intermediate-level" gyr mutations of 1.3 (0.6
      3.1), which did not reach statistical significance. The gyr mutations were not
      different than culture-based FQ drug susceptibility testing in predicting the
      hazard of death or treatment failure and may be superior. Conclusions: FQ
      molecular-based diagnostic tests may better predict treatment response than
      traditional drug susceptibility testing and open avenues for personalizing TB
      therapy.

PMID- 29017251
TI  - Cumulative Incidence and Incidence Rate Ratio for Estimation of Risk of
      Tuberculosis in Patients With Cancer.

PMID- 29017250
TI  - Reply to Dobler.

PMID- 29017252
TI  - Erratum.

PMID- 29017249
TI  - Characterization of Aerosols Generated During Patient Care Activities.
AB  - Background: Questions remain about the degree to which aerosols are generated
      during routine patient care activities and whether such aerosols could transmit
      viable pathogens to healthcare personnel (HCP). The objective of this study was
      to measure aerosol production during multiple patient care activities and to
      examine the samples for bacterial pathogens. Methods: Five aerosol
      characterization instruments were used to measure aerosols during 7 patient care
      activities: patient bathing, changing bed linens, pouring and flushing liquid
      waste, bronchoscopy, noninvasive ventilation, and nebulized medication
      administration (NMA). Each procedure was sampled 5 times. An SKC BioSampler was
      used for pathogen recovery. Bacterial cultures were performed on the sampling
      solution. Patients on contact precautions for drug-resistant organisms were
      selected for most activity sampling. Any patient undergoing bronchoscopy was
      eligible. Results: Of 35 sampling episodes, only 2 procedures showed a
      significant increase in particle concentrations over baseline: NMA and
      bronchoscopy with NMA. Bronchoscopy without NMA and noninvasive ventilation did
      not generate significant aerosols. Of 78 cultures from the impinger samples, 6 of
      28 baseline samples (21.4%) and 14 of 50 procedure samples (28.0%) were positive.
      Conclusions: In this study, significant aerosol generation was only observed
      during NMA, both alone and during bronchoscopy. Minimal viable bacteria were
      recovered, mostly common environmental organisms. Although more research is
      needed, these data suggest that some of the procedures considered to be aerosol
      generating may pose little infection risk to HCP.

PMID- 29017254
TI  - Keeping Up With a World in Motion: Screening Strategies for Migrating
      Populations.

PMID- 29017253
TI  - Rapid Clearance and Frequent Reinfection With Enteric Pathogens Among Children
      With Acute Diarrhea in Zanzibar.
AB  - Background: Acute infectious gastroenteritis is an important cause of illness and
      death among children in low-income countries. In addition to rotavirus
      vaccination, actions to improve nutrition status, sanitation, and water quality
      are important to reduce enteric infections, which are frequent also among
      asymptomatic children. The aim of this study was to investigate if the high
      prevalence of these infections reflects that they often are not cleared properly
      by the immune response or rather is due to frequent pathogen exposure. Methods:
      Rectal swabs were collected at time of acute diarrhea and 14 days later from 127
      children, aged 2-59 months and living in rural Zanzibar, and were analyzed by
      real-time polymerase chain reaction targeting multiple pathogens. Results: At
      baseline, detection rates >20% were found for each of enterotoxigenic Escherichia
      coli, Shigella, Campylobacter, Cryptosporidium, norovirus GII, and adenovirus. At
      follow-up, a large proportion of the infections had become cleared (34-100%), or
      the pathogen load reduced, and this was observed also for agents that were
      presumably unrelated to diarrhea. Still, the detection frequencies at follow-up
      were for most agents as high as at baseline, because new infections had been
      acquired. Neither clearance nor reinfection was associated with moderate
      malnutrition, which was present in 21% of the children. Conclusions: Children
      residing in poor socioeconomic conditions, as in Zanzibar, are heavily exposed to
      enteric pathogens, but capable of rapidly clearing causative and coinfecting
      pathogens.

PMID- 29017256
TI  - Erratum.

PMID- 29017255
TI  - Systematic Tuberculosis Screening in Asylum Seekers in Italy.
AB  - The preliminary findings of a tuberculosis (TB) screening of asylum seekers
      performed in a reception center located in northern Italy reveal a post-entry
      screening prevalence rate of 535 per 100000 individuals screened. This result
      shows that systematic use of chest radiography is a useful tool for active TB
      screening among asylum seekers in Italy.

PMID- 29017257
TI  - Erratum.

PMID- 29017258
TI  - A 63-Year-Old Korean Woman With Abnormal Magnetic Resonance Imaging Results.

PMID- 29017259
TI  - A 63-Year-Old Korean Woman With Abnormal Magnetic Resonance Imaging Results.

PMID- 29017260
TI  - Waterpipe Use in the Middle East and North Africa: Data From the Breathe Study.
AB  - Introduction: In recent decades, waterpipe use has gained popularity, notably in
      the Middle East and North Africa (MENA) region. This study describes waterpipe
      use and characteristics of waterpipe users among the general population of the
      MENA region. Methods: This study was a sub-analysis of the BREATHE study, a cross
      sectional survey of chronic obstructive respiratory disease conducted in the
      general population of 11 countries of the MENA region. The study population
      consisted of subjects aged >=40 years who completed the screening questionnaire
      and who reported waterpipe use (alone or with cigarettes). This questionnaire
      collected data on demographics, self-reported respiratory symptoms
      (breathlessness and productive cough), smoking habits (cigarettes or waterpipe)
      and diagnosis of chronic obstructive respiratory disease, chronic bronchitis or
      emphysema. Results: Of the 62 086 subjects screened in the BREATHE study,
      waterpipe use was reported by 2173 subjects (3.5% [95% CI: 3.4%-3.6%]), of whom
      934 subjects (43.0%) smoked both waterpipes and cigarettes. The majority of
      waterpipe users were men (82%) and aged from 40 to 49 years (53.7%). Over 90% of
      users smoked their waterpipe for >=1 hour per day. Waterpipe use was associated
      with an increased risk of productive cough (odds ratio [OR]: 1.49),
      breathlessness (OR: 1.33), and chronic bronchitis (OR: 1.43), independently of
      the risk associated with cigarette smoking. In subjects using waterpipe alone (N
      = 1239), breathlessness was the most frequently self-reported symptom (11.3%),
      followed by productive cough (6.0%) and chronic bronchitis (2.2%). Conclusions:
      Waterpipe smoking in the region is widespread and is associated with an increased
      risk of respiratory pathology independently of cigarette smoking. Implications:
      This large general population study reports an elevated risk of respiratory
      disease associated with waterpipe use independently of cigarette smoking; this
      finding emphasizes the need for public health policies to curtail the growing
      spread of waterpipe use by young people in the MENA region.

PMID- 29017261
TI  - The Evolving Tobacco Product and Tobacco Control Policy Landscapes: Understanding
      Complex and Interactive Effects to Avoid Leaving Vulnerable Populations Behind.

PMID- 29017263
TI  - Progress in the Fight Against Multidrug-Resistant Bacteria 2005-2016: Modern
      Noninferiority Trial Designs Enable Antibiotic Development in Advance of Epidemic
      Bacterial Resistance.
AB  - From a public health perspective, new antibacterial agents should be evaluated
      and approved for use before widespread resistance to existing agents emerges.
      However, for multidrug-resistant pathogens, demonstration of superior efficacy of
      a new agent over a current standard-of-care agent is routinely feasible only when
      epidemic spread of these dangerous organisms has already occurred. One solution
      to enable proactive drug development is to evaluate new antibiotics with improved
      in vitro activity against MDR pathogens using recently updated guidelines for
      active control, noninferiority trials of selected severe infections caused by
      more susceptible pathogens. Such trials are feasible because they enroll patients
      with infections due to pathogens with a "usual drug resistance" phenotype that
      will be responsive to widely registered standard-of-care comparator antibiotics.
      Such anticipatory drug development has constructively reshaped the antibiotic
      pipeline and offers the best chance of making safe and efficacious antibiotics
      available to the public ahead of epidemic resistance.

PMID- 29017264
TI  - Application of "Precision Medicine" Through the Molecular Characterization of
      Extensively Drug-Resistant Klebsiella pneumoniae in a Multivisceral Transplant
      Patient.

PMID- 29017266
TI  - Reply to Macesic et al.

PMID- 29017267
TI  - Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae: De Novo or
      Drug Exposure?

PMID- 29017262
TI  - Ceftolozane-Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas
      aeruginosa Infections: Clinical Effectiveness and Evolution of Resistance.
AB  - Background: Data on the use of ceftolozane-tazobactam and emergence of
      ceftolozane-tazobactam resistance during multidrug resistant (MDR)-Pseudomonas
      aeruginosa infections are limited. Methods: We performed a retrospective study of
      21 patients treated with ceftolozane-tazobactam for MDR-P. aeruginosa infections.
      Whole genome sequencing and quantitative real-time polymerase chain reaction were
      performed on longitudinal isolates. Results: Median age was 58 years; 9 patients
      (43%) were transplant recipients. Median simplified acute physiology score-II
      (SAPS-II) was 26. Eighteen (86%) patients were treated for respiratory tract
      infections; others were treated for bloodstream, complicated intraabdominal
      infections, or complicated urinary tract infections. Ceftolozane-tazobactam was
      discontinued in 1 patient (rash). Thirty-day all-cause and attributable mortality
      rates were 10% (2/21) and 5% (1/21), respectively; corresponding 90-day mortality
      rates were 48% (10/21) and 19% (4/21). The ceftolozane-tazobactam failure rate
      was 29% (6/21). SAPS-II score was the sole predictor of failure. Ceftolozane
      tazobactam resistance emerged in 3 (14%) patients. Resistance was associated with
      de novo mutations, rather than acquisition of resistant nosocomial isolates. ampC
      overexpression and mutations were identified as potential resistance
      determinants. Conclusions: In this small study, ceftolozane-tazobactam was
      successful in treating 71% of patients with MDR-P. aeruginosa infections, most of
      whom had pneumonia. The emergence of ceftolozane-tazobactam resistance in 3
      patients is worrisome and may be mediated in part by AmpC-related mechanisms.
      More research on treatment responses and resistance during various types of MDR
      P. aeruginosa infections is needed to define ceftolozane-tazobactam's place in
      the armamentarium.

PMID- 29017265
TI  - Antibiotic Overconsumption in Pregnant Women With Urinary Tract Symptoms in
      Uganda.
AB  - Background: Urinary tract infections (UTIs) are one of the most common bacterial
      infections in women. During pregnancy physiological changes, like frequency,
      mimic UTI symptoms, and therefore bacteriological cultures are needed to confirm
      the diagnosis. However, in developing countries antibiotic therapy is commonly
      initiated without culture confirmation. Methods: We investigated the prevalence
      of bacteriuria among pregnant women with and without UTI symptoms in Uganda. In
      total 2 562 urine samples were evaluated with nitrite and leukocyte esterase
      tests, using urine culture and/or dipslide with species identification as
      reference. Results: The prevalence of culture-proven UTI among pregnant women
      with UTI symptoms was 4%. Since treatment is initiated based only on the presence
      of symptoms, 96% were erroneously given antibiotics. Further, there is a high
      prevalence of resistance to commonly used antibiotics, with 18 % ESBL and 36 %
      multidrug resistant Escherichia coli strains. Nitrite, leukocyte esterase tests,
      and urine microscopy alone were of poor diagnostic value. Using dipslide,
      gynecologists and nurses, not trained in microbiology, were mostly able to
      identify E. coli and negative cultures. Mixed Gram-negative flora, suggesting
      fecal contamination was, however, in the majority of cases interpreted as a
      single pathogenic bacterium and would have resulted in antibiotic treatment.
      Conclusions: To prevent excessive use of antibiotics, dipslide possibly supported
      by a combination of nitrite and leukocyte esterase tests can be used. Trained
      frontline health care professionals correctly diagnosed E. coli UTI and negative
      urine cultures, which would help preventing antibiotic misuse. In addition,
      regular screening for antibiotic resistance would improve correct treatment.

PMID- 29017268
TI  - The Spectrum and Burden of Influenza-Associated Neurological Disease in Children:
      Combined Encephalitis and Influenza Sentinel Site Surveillance From Australia,
      2013-2015.
AB  - Background: There are few longitudinal studies of seasonal influenza-associated
      neurological disease (IAND) and none from the Southern Hemisphere. Methods: We
      extracted prospectively acquired Australian surveillance data from 2 studies
      nested within the Paediatric Active Enhanced Disease Surveillance (PAEDS)
      network: the Influenza Complications Alert Network (FluCAN) study and the
      Australian Childhood Encephalitis (ACE) study between 2013 and 2015. We described
      the clinical features and severity of IAND in children, including influenza
      associated encephalitis/encephalopathy (IAE). We calculated the proportion of
      hospitalized influenza that is associated with IAND and IAE, and incidence of
      IAE. Results: Over 3 influenza seasons, we identified 54 cases of IAND at 2
      tertiary children's hospitals from Australia that accounted for 7.6% of
      hospitalized influenza. These included 10 cases of IAE (1.4% hospitalized
      influenza). The mean annual incidence of IAE among Australian children (aged <=14
      years) was 2.8 per 1000000. The spectrum of IAND was broad and included IAE (n =
      10) including distinct acute encephalopathy syndromes, simple febrile seizures (n
      = 14), other seizures (n = 16), acute ataxia (n = 4), and other subacute
      syndromes (transverse myelitis [n = 1], opsoclonus myoclonus [n = 1]). Two-thirds
      of children with IAND were aged <=4 years; less than half had preexisting
      neurological disease or other risk factors for severe influenza. IAE caused death
      or neurological morbidity in half of cases. Conclusions: Seasonal influenza is an
      important cause of acute neurological disease in Australian children. The
      spectrum of seasonal IAND appears similar to that described during the 2009 H1N1
      pandemic. IAE is associated with high morbidity and mortality.

PMID- 29017270
TI  - Erratum.

PMID- 29017271
TI  - Erratum.

PMID- 29017272
TI  - Erratum.

PMID- 29017273
TI  - Erratum.

PMID- 29017274
TI  - Erratum.

PMID- 29017275
TI  - The Response of the Peer Review System to the Ebola and Zika Virus Epidemic.

PMID- 29017276
TI  - Reply to Cobussen et al.

PMID- 29017269
TI  - Cancer-Attributable Mortality Among People With Treated Human Immunodeficiency
      Virus Infection in North America.
AB  - Background: Cancer remains an important cause of morbidity and mortality in
      people with human immunodeficiency virus (PWHIV) on effective antiretroviral
      therapy (ART). Estimates of cancer-attributable mortality can inform public
      health efforts. Methods: We evaluated 46956 PWHIV receiving ART in North American
      HIV cohorts (1995-2009). Using information on incident cancers and deaths, we
      calculated population-attributable fractions (PAFs), estimating the proportion of
      deaths due to cancer. Calculations were based on proportional hazards models
      adjusted for age, sex, race, HIV risk group, calendar year, cohort, CD4 count,
      and viral load. Results: There were 1997 incident cancers and 8956 deaths during
      267145 person-years of follow-up, and 11.9% of decedents had a prior cancer. An
      estimated 9.8% of deaths were attributable to cancer (cancer-attributable
      mortality rate 327 per 100000 person-years). PAFs were 2.6% for AIDS-defining
      cancers (ADCs, including non-Hodgkin lymphoma, 2.0% of deaths) and 7.1% for non
      AIDS-defining cancers (NADCs: lung cancer, 2.3%; liver cancer, 0.9%). PAFs for
      NADCs were higher in males and increased strongly with age, reaching 12.5% in
      PWHIV aged 55+ years. Mortality rates attributable to ADCs and NADCs were highest
      for PWHIV with CD4 counts <100 cells/mm3. PAFs for NADCs increased during 1995
      2009, reaching 10.1% in 2006-2009. Conclusions: Approximately 10% of deaths in
      PWHIV prescribed ART during 1995-2009 were attributable to cancer, but this
      fraction increased over time. A large proportion of cancer-attributable deaths
      were associated with non-Hodgkin lymphoma, lung cancer, and liver cancer. Deaths
      due to NADCs will likely grow in importance as AIDS mortality declines and PWHIV
      age.

PMID- 29017277
TI  - Short Course of Empirical Gentamicin in Patients With Severe Sepsis and Septic
      Shock in the ICU: A Benefit or a Burden?

PMID- 29017281
TI  - Erratum.

PMID- 29017279
TI  - Population-Level Herd Protection of Males From a Female Human Papillomavirus
      Vaccination Program: Evidence from Australian Serosurveillance.
AB  - Background: Australia instituted funded female human papillomavirus (HPV)
      immunization in 2007, followed by a targeted male vaccination program in 2013. To
      date, Australia is one of only several countries with a funded male HPV
      immunization program. In 2012-2013, we conducted a survey of HPV seroprevalence
      in males to assess whether or not a herd impact of female vaccination could be
      observed. Methods: We conducted a cross-sectional study of de-identified residual
      diagnostic test serum samples from males aged 15-39 years from laboratories in 3
      Australian states and calculated the proportion seropositive to HPV types 6, 11,
      16, and 18. We compared type-specific results by age group against those from a
      baseline 2005 Australian HPV serosurvey. Results: There were decreases in
      proportion seropositive for every HPV type across all age groups, many
      statistically significant. The largest decrease was observed for HPV-11, with
      decreases of 8- and 9-fold for ages 20-29 and 30-39 years, respectively. Despite
      substantial reductions in seroprevalence, at least 9% of males were seropositive
      for at least 1 of the 4 HPV types. Conclusions: This is the first serosurvey
      confirming broad population-level impact in males from female HPV vaccination.
      Our research may assist policy makers considering implementing HPV vaccination
      programs.

PMID- 29017280
TI  - Immunogenicity of the 13-Valent Pneumococcal Conjugate Vaccine in Older Adults
      With and Without Comorbidities in the Community-Acquired Pneumonia Immunization
      Trial in Adults (CAPiTA).
AB  - Background: In the randomized controlled Community-Acquired Pneumonia
      Immunization Trial in Adults (CAPiTA), the efficacy of the 13-valent pneumococcal
      conjugate vaccine (PCV13) against first episodes of vaccine-type community
      acquired pneumonia in adults aged >=65 years was 46%. The long-term
      immunogenicity of PCV13 in pneumococcal vaccine-naive older adults was
      investigated as part of CAPiTA. Methods: We determined the immune responses to
      PCV13 before and at 1, 12, and 24 months after vaccination in 1006 PCV13
      recipients and 1005 controls with 3 age-stratified study participant cohorts.
      PCV13 serotype-specific opsonophagocytic activity (OPA) titers and immunoglobulin
      G (IgG) concentrations were determined. Results: Sample collection completeness
      was at least 93.4% at each time point. In all 3 age categories, a single dose of
      PCV13 elicited OPA titers and IgG concentrations for all 13 serotypes that were
      significantly higher than baseline and the corresponding responses in the placebo
      group at all time points. In the eldest subjects (>=80 years of age at
      vaccination), OPA titers and IgG concentrations remained above baseline and there
      was no apparent difference in OPA titers and IgG concentrations between those
      with self-reported comorbidities and healthy older adults. However, the study was
      not powered to determine statistical significance between different age and
      comorbidity groups, and thus these results are exploratory. Conclusions: In
      immunocompetent adults >=65 years of age, PCV13 elicits significant increases in
      OPA titers and IgG concentrations that persist 2 years postvaccination for all 13
      serotypes, regardless of age and comorbidity. Clinical Trials Registration:
      NCT00744263.

PMID- 29017278
TI  - Favipiravir and Ribavirin Treatment of Epidemiologically Linked Cases of Lassa
      Fever.
AB  - Two patients with Lassa fever are described who are the first human cases treated
      with a combination of ribavirin and favipiravir. Both patients survived but
      developed transaminitis and had prolonged detectable virus RNA in blood and
      semen, suggesting that the possibility of sexual transmission of Lassa virus
      should be considered.

PMID- 29017282
TI  - Plasma Cytokine Predictors of Tuberculosis Recurrence in Antiretroviral-Treated
      Human Immunodeficiency Virus-infected Individuals from Durban, South Africa.
AB  - Background: Immune correlates of tuberculosis (TB) risk in populations infected
      with human immunodeficiency virus (HIV) remain understudied, despite HIV being
      associated with a high burden of TB disease. Here we describe plasma cytokine
      correlates of TB recurrence in a well-characterized cohort of HIV-infected
      individuals on antiretroviral therapy (ART) with a history of prior TB cure.
      Methods: Study participants were drawn from a prospective cohort study initiated
      at the conclusion of a randomized clinical trial in which individuals presented
      with untreated HIV infection and active pulmonary TB. At baseline, ART was
      initiated, and TB successfully cured. Participants were screened for TB
      recurrence quarterly for up to 4 years. TB recurrent cases (n = 63) were matched
      to controls (n = 123) on sex, study arm assignment in the original trial, and
      month of enrollment with a subset of cases sampled longitudinally at several time
      points. Results: Three cytokines were associated with increased rates of TB
      recurrence in univariate models: interleukin 6 (IL6) (odds ratio [OR] 2.66, 95%
      confidence interval [CI] 1.34-5.28, P = .005), IP10 (OR 4.62, 95% CI 1.69-12.65,
      P = .003), monokine induced by IFN-gamma (MIG) (OR 3.11, 95% CI 1.10-8.82, P =
      .034). Conversely, interferon beta (IFNbeta) was associated with decreased TB
      risk (OR 0.34, 95% CI 0.13-0.87, P = .025). Following multivariate analyses
      adjusting for covariates IL6, interleukin 1beta (IL1beta), and interleukin
      1Ralpha (IL1Ralpha) were associated with increased risk and IFNbeta with
      decreased TB risk. Longitudinal analysis showed that levels of many TB-associated
      markers, including IL6, IP10, sCD14, and interferon gamma (IFNgamma) are reduced
      following TB treatment. Conclusion: These data show that TB recurrence, in HIV
      infected individuals on ART is predicted by biomarkers of systemic inflammation,
      many of which are implicated in more rapid HIV disease progression. Clinical
      Trials Registration: NCT 01539005.

PMID- 29017285
TI  - Reply to Corona and Cattaneo.

PMID- 29017284
TI  - Incidence of Norovirus-Associated Diarrhea and Vomiting Disease Among Children
      and Adults in a Community Cohort in the Peruvian Amazon Basin.
AB  - Background: Data on norovirus epidemiology among all ages in community settings
      are scarce, especially from tropical settings. Methods: We implemented active
      surveillance in 297 households in Peru from October 2012 to August 2015 to assess
      the burden of diarrhea and acute gastroenteritis (AGE) due to norovirus in a
      lower-middle-income community. During period 1 (October 2012-May 2013), we used a
      "traditional" diarrhea case definition (>=3 loose/liquid stools within 24 hours).
      During period 2 (June 2013-August 2015), we used an expanded case definition of
      AGE (by adding >=2 vomiting episodes without diarrhea or 1-2 vomiting episodes
      plus 1-2 loose/liquid stools within 24 hours). Stool samples were tested for
      norovirus by reverse-transcription polymerase chain reaction. Results: During
      period 1, overall diarrhea and norovirus-associated diarrhea incidence was
      37.2/100 person-years (PY) (95% confidence interval [CI], 33.2-41.7) and 5.7/100
      PY (95% CI, 3.9-8.1), respectively. During period 2, overall AGE and norovirus
      associated AGE incidence was 51.8/100 PY (95% CI, 48.8-54.9) and 6.5/100 PY (95%
      CI, 5.4-7.8), respectively. In both periods, children aged <2 years had the
      highest incidence of norovirus. Vomiting without diarrhea occurred among
      norovirus cases in participants <15 years old, but with a higher proportion among
      children <2 years, accounting for 35% (7/20) of all cases in this age group.
      Noroviruses were identified in 7% (23/335) of controls free of gastroenteric
      symptoms. Conclusions: Norovirus was a significant cause of AGE in this
      community, especially among children <2 years of age. Inclusion of vomiting in
      the case definition resulted in a 20% improvement for detection of norovirus
      cases.

PMID- 29017283
TI  - Reduced Severity of Pertussis in Persons With Age-Appropriate Pertussis
      Vaccination-United States, 2010-2012.
AB  - Background: In 2012, >48000 pertussis cases were reported in the United States.
      Many cases occurred in vaccinated persons, showing that pertussis vaccination
      does not prevent all pertussis cases. However, pertussis vaccination may have an
      impact on disease severity. Methods: We analyzed data on probable and confirmed
      pertussis cases reported through Enhanced Pertussis Surveillance (Emerging
      Infections Program Network) between 2010 and 2012. Surveillance data were
      collected through physician and patient interview and vaccine registries. We
      assessed whether having received an age-appropriate number of pertussis vaccines
      (AAV) (for persons aged >=3 months) was associated with reduced odds of
      posttussive vomiting, a marker of more clinically significant illness, or of
      severe pertussis (seizure, encephalopathy, pneumonia, and/or hospitalization).
      Adjusted odds ratios were calculated using multivariable logistic regression.
      Results: Among 9801 pertussis patients aged >=3 months, 77.6% were AAV. AAV
      status was associated with a 60% reduction in odds of severe disease in children
      aged 7 months-6 years in multivariable logistic regression and a 30% reduction in
      odds of posttussive vomiting in persons aged 19 months-64 years. Conclusions:
      Serious pertussis symptoms and complications are less common among AAV pertussis
      patients, demonstrating that the positive impact of pertussis vaccination extends
      beyond decreasing risk of disease.

PMID- 29017286
TI  - Dosing Colistin Properly: Let's Save "Our Last Resort Old Drug!"

PMID- 29017287
TI  - Neal S. Kleiman MD: Cardiologist, climber, scientist, survivor.

PMID- 29017288
TI  - Management of arrhythmias: NOACs, digoxin, alcohol, light, and devices.

PMID- 29017289
TI  - Comparative evaluation of the efficacy of lignocaine containing topical
      anesthetic agents during extraction of deciduous anterior teeth.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of 2%, 4%
      lignocaine, Eutectic Mixture of Local Anesthetics (EMLA) mixture and precaine
      topical anesthetic agents (with 1:1,000,000 epinephrine) during the extraction of
      deciduous anterior tooth. METHODS: Eighty patients with preshedding mobility of
      deciduous anterior tooth were divided randomly into four groups. Lignocaine, in
      amount of 2% and 4%, precaine and EMLA topical anesthetic agents were applied and
      the tooth was extracted. VAS has been used to assess the subjective pain while
      Wong-Baker Faces Scale and SEM Pain Scale have been used to record the objective
      pain to check the efficacy of these topical anesthetic agents. SPSS ver.17 was
      used for statistical analysis. Group comparison was done by ANOVA (Fishers F
      test) and inter comparison was done by Tukeys t-test. RESULTS: Based on the
      scoring criteria of VAS, SEM and Wong Bakers facial pain scales, precaine had
      best scores followed by EMLA mixture, 4% lignocaine, and then 2 % lignocaine
      during extraction of primary anterior teeth with preshedding mobility.
      CONCLUSIONS: The efficacy of precaine was superior compared to EMLA mixture
      followed by 4% lignocaine and 2% Lignocaine respectively.

PMID- 29017291
TI  - Can Patient Education with a Smartphone Application Improve the Quality of Bowel
      Preparation for Colonoscopy?

PMID- 29017290
TI  - Role of Advanced Endoscopic Imaging Techniques in the Management of Inflammatory
      Bowel Disease.
AB  - Endoscopy plays a crucial role in the management of inflammatory bowel disease
      (IBD) in terms of diagnosis, monitoring of mucosal status, and surveillance of
      colitis-associated neoplasia. Mucosal healing evaluated by endoscopy has been
      recognized as the target of treatment in the era of powerful biologics therapy.
      The optimal modality for identifying dysplasia in IBD has yet to be well defined.
      Increasing progress has recently been made in endoscopic technologies to more
      accurately assess mucosal inflammation and more effectively detect dysplasia.
      Here we review the data of advanced endoscopic imaging techniques such as
      chromoendoscopy, virtual chromoendoscopy, endocytoscopy, and confocal laser
      endomicroscopy in the management of IBD.

PMID- 29017292
TI  - Carbon Dioxide Insufflation in Endoscopic Submucosal Dissection: Is It an Urgent
      Need?

PMID- 29017294
TI  - Identification of Ulceration in Early Gastric Cancer before Resection is Not
      Easy: Need for a New Guideline for Endoscopic Submucosal Dissection Indication
      Based on Endoscopic Image.

PMID- 29017293
TI  - Endoscopic Therapeutic Approach for Dysplasia in Inflammatory Bowel Disease.
AB  - Long-standing intestinal inflammation in patients with inflammatory bowel disease
      (IBD) induces dysplastic change in the intestinal mucosa and increases the risk
      of subsequent colorectal cancer. The evolving endoscopic techniques and
      technologies, including dye spraying methods and high-definition images, have
      been replacing random biopsies and have been revealed as more practical and
      efficient for detection of dysplasia in IBD patients. In addition, they have
      potential usefulness in detailed characterization of lesions and in the
      assessment of endoscopic resectability. Most dysplastic lesions without an
      unclear margin, definite ulceration, non-lifting sign, and high index of
      malignant change with suspicion for lymph node or distant metastases can be
      removed endoscopically. However, endoscopic resection of dysplasia in chronic IBD
      patients is usually difficult because it is often complicated by submucosal
      fibrosis. In patients with dysplasias that demonstrate submucosa fibrosis or a
      large size (>=20 mm), endoscopic submucosal dissection (ESD) or ESD with snaring
      (simplified or hybrid ESD) is an alternative option and may avoid a colectomy.
      However, a standardized endoscopic therapeutic approach for dysplasia in IBD has
      not been established yet, and dedicated specialized endoscopists with interest in
      IBD are needed to fully investigate recent emerging techniques and technologies.

PMID- 29017296
TI  - Optimal Evaluation of Suspected Choledocholithiasis: Does This Patient Really
      Have Choledocholithiasis?

PMID- 29017295
TI  - Balloon-Assisted Enteroscopy and Capsule Endoscopy in Suspected Small Bowel
      Crohn's Disease.
AB  - Inflammatory bowel diseases are idiopathic inflammatory diseases of two main
      types, Crohn's disease and ulcerative colitis. Crohn's disease can affect the
      entire gastrointestinal tract, and the distal ileum is involved in up to 70% of
      patients. Moreover, Crohn's disease in one-quarter to one-third of patients
      involves isolation of the small bowel. Due to the nonspecific symptoms and
      anatomical location of the disease, small bowel Crohn's disease is a phenotype
      that is particularly difficult to manage. Since the introduction of capsule
      endoscopy in 2000 and balloon-assisted enteroscopy in the 21st century, it is now
      possible to directly inspect for small bowel Crohn's disease. However, the new
      modalities still have limitations, such as capsule retention and invasiveness of
      balloon-assisted enteroscopy. The diagnostic yields of both capsule endoscopy and
      balloon-assisted enteroscopy are high for patients with suspected small bowel
      Crohn's disease. Therefore, earlier use of capsule endoscopy or balloon-assisted
      enteroscopy can help with the diagnosis and earlier treatment of these patients
      to avert possible disastrous outcomes.

PMID- 29017297
TI  - Endoscopic Balloon Dilation for Crohn's Disease-Associated Strictures.
AB  - Management of intestinal strictures associated with Crohn's disease (CD) is
      clinically challenging despite advanced medical therapy directed toward mucosal
      healing to positively influence the natural course of CD-associated
      complications. Although medical therapy is available for inflammatory strictures,
      therapy of fibrostenotic strictures is the domain of surgery and endoscopy.
      Endoscopic balloon dilation (EBD) has been recognized as a well-established first
      line procedure in terms of safety and efficacy. Although surgery is a valuable
      treatment modality for the management of CD-related strictures, EBD can help
      prevent multiple surgical interventions, which might in the long-term lead to a
      risk of short bowel syndrome. In this review we discuss requirements, techniques,
      safety, short- and long-term outcomes, as well as combinations of this procedure
      with surgical and medical treatment in CD-associated intestinal strictures.

PMID- 29017298
TI  - Space Available for the Cervical Spinal Cord of Asymptomatic Adult Nigerians.
AB  - OBJECTIVE: The space available for the spinal cord (SAC) is a measure of spinal
      cord functional reserve and may vary in different societies. The objective of
      this study is to measure normal SAC at each subaxial cervical disc level of
      asymptomatic adult Nigerians and to compare obtained values with published
      studies worldwide. METHODS: This is a prospective, cross-sectional study using
      magnetic resonance imaging facility at Memfys Hospital Enugu, from 2012 to 2013.
      Disc level measurement of midsagittal spinal canal and cord of randomly selected
      102 consenting asymptomatic adults, 21 to 50 years. Literature search of related
      studies worldwide was used to compare with the current study. Analysis was done
      using inferential and descriptive statistics. RESULTS: Average SAC values were
      4.9+/-1.4 mm (C3/4), 4.5+/-1.2 mm (C4/5), 4.6+/-1.4 mm (C5/6), and 4.9+/-1.2 mm
      (C6/7). In 21-30 years group, SAC was 5.4+/-0.6 mm(C3/4), 4.9+/-0.6 mm(C4/5),
      4.9+/-0.6 mm(C5/6), and 5.1+/-0.5 mm(C6/7). In 31-40 years group, SAC was 5.4+/
      0.5 mm(C3/4), 4.6+/-0.5 mm (C4/5), 4.9+/-0.6 mm (C5/6), and 5.3+/-0.6 mm (C6/7);
      but among 41-50 years group, SAC was 3.8+/-0.6 mm (C3/4), 3.9+/-0.6 mm (C4/5),
      3.6+/-0.6 mm (C5/6), and 4.3+/-0.6 mm (C6/7). In females SAC was 4.9+/-1.3
      mm(C3/4), 4.5+/-1.2 mm(C4/5), 4.6+/-1.2 mm(C5/6), and 4.8+/-1.1 mm (C6/7). In
      males, SAC was 4.9+/-1.4 mm(C3/4), 4.6+/-1.2 mm(C4/5), 4.5+/-1.5 mm(C5/6), and
      5.1+/-1.3 mm(C6/7). From analysis of variance, impact of age on SAC was 0.118
      (p=0.001) while gender had 0.078 (p=0.223). SAC at each level has positive
      correlation of 0.6 to 0.7 with adjacent levels (p<0.0001). Comparing this result
      with studies worldwide, our population has lower SAC values than others.
      CONCLUSION: C4/5 and C5/6 are narrowest subaxial cervical spine levels and
      probably explain preponderance of C4/5 and C5/6 cord injury. There may be higher
      incidence of congenital canal stenosis predisposing to worse outcome following
      cervical spine injury or degenerative diseases in this study population. This is
      different from European series but similar to Japanese.

PMID- 29017300
TI  - Long-term Clinical and Radiological Outcomes after Central Decompressive
      Laminoplasty for Lumbar Spinal Stenosis.
AB  - OBJECTIVE: There are many technical modifications of decompressive lumbar
      laminectomy. The purpose of this study was to report long-term clinical and
      radiological outcomes of central decompressive laminoplasty (CDL), the
      corresponding author's own modification of lumbar laminectomy for lumbar spinal
      stenosis (LSS). METHODS: Among 100 patients who underwent CDL by a single surgeon
      between December 2010 and March 2014, 68 patients were included in this study.
      Mean follow-up time was 37.7 months. Clinical and radiological data were gathered
      prospectively and reviewed retrospectively. Clinical outcome was measured by
      using visual analog scale (VAS) for back/buttock and leg, and the Oswestry
      Disability Index (ODI). Radiological outcome was measured by neutral slippage
      percentage, dynamic slippage percentage, and dynamic intervertebral angel on
      sagittal X-ray. Outcomes after CDL were assessed by changes of clinical and
      radiological parameters from the baseline. Mixed effect model with random
      patients' effect as used to test for differences in the repeated measured
      clinical and radiological data. RESULTS: The patients had no serious
      complications with an uneventful recovery during the early postoperative period.
      In the early postoperative period, VAS scores for back/buttock and leg improved
      significantly and were kept with time (p<0.001). ODI also improved significantly
      during the postoperative follow-up period (p<0.001). The radiologic parameters
      were well maintained and showed no progression of instability. During the follow
      up, a case of herniated disc at same level recurrence was noted after lifting
      trauma, and 2 adjacent foraminal stenosis needed additional surgery. CONCLUSION:
      CDL provides long-term pain relief and functional restoration without progression
      of radiological instability.

PMID- 29017299
TI  - Variation of C-Reactive Protein and White Blood Cell Counts in Spinal Operation:
      Primary Fusion Surgery Versus Revision Fusion Surgery.
AB  - OBJECTIVE: Serum C-reactive protein (CRP) concentrations and white blood cell
      (WBC) count are commonly used to identify postoperative wound infections. We
      investigated whether changes in serum CRP levels and WBC counts actually differed
      between patients undergoing revision spinal fusion surgery and those undergoing a
      primary fusion. METHODS: Patients who underwent posterolateral fusion (PLF)
      surgery at Pusan National University Yangsan Hospital between October 2013 and
      April 2015 were considered for this study. Sixty-seven patients with primary
      lumbar PLF (pPLF) and 21 with revision PLF (rPLF) were enrolled. A retrospective
      assessment of preoperative and postoperative CRP levels and WBC count was
      undertaken. Also, we gathered peak CRP day, and CRP normalization days.
      Comorbidity data were also obtained to evaluate any effects on the course of CRP
      and WBC count postoperatively. RESULTS: CRP levels peaked at 3 days after
      surgery. The maximum CRP values recorded for each group: 4.17 (standard deviation
      [SD], 4.18) mg/dL and 4.88 (SD, 3.03) mg/dL for pPLF and rPLF. This difference
      was not statistically significant (p=0.24). A rapid fall in CRP within 5-9 days
      was observed for both groups. CONCLUSION: Out of our expectation, changes in CRP
      levels after spinal fusion surgery follow the same course regardless of whether
      it is a revision operation or not. Because of this result, both the primary PLF
      surgery and revision PLF surgery should be monitored using CRP in the similar way
      and the antibiotic administration should be determined.

PMID- 29017301
TI  - Pelvic Incidence Can Be Changed not only by Age and Sex, but also by Posture Used
      during Imaging.
AB  - OBJECTIVE: Computed tomography (CT), rather than conventional 2-dimensional
      radiography, was used to scan and measure pelvic parameters. The results were
      compared with measurements using X-ray. METHODS: Pelvic parameters were measured
      using both CT and X-ray in 254 patients who underwent both abdomino-pelvic CT and
      X-ray at the pelvic site. We assessed the similarity of the pelvic parameters
      between the 2 exams, as well as the correlations of pelvic parameters with sex
      and age. RESULTS: The mean values of the subjects' pelvic parameters measured on
      X-ray were: sacral slope (SS), 31.6 degrees ; pelvic tilt (PT), 18.6 degrees ;
      and pelvic incidence (PI), 50.2 degrees . The mean values measured on CT were:
      SS, 35.1 degrees ; PT, 11.9 degrees ; and PI, 47.0 degrees . PT was found to be
      4.07 degrees  higher on X-ray and 2.98 degrees  higher on CT in women, with these
      differences being statistically significant (p<0.001, p<0.001). PI was 4.10
      degrees  higher on X-ray and 2.78 degrees  higher on CT in women, with these
      differences also being statistically significant (p<0.001, p=0.009). We also
      observed a correlation between age and PI. For men, this correlation coefficient
      was 0.199 measured using X-ray and 0.184 measured using CT. For women, this
      correlation coefficient was 0.423 measured using X-ray and 0.372 measured using
      CT. CONCLUSION: When measured using CT compared to X-ray, SS increased by 3.5
      degrees , PT decreased by 6.7 degrees , and PI decreased by 3.2 degrees . There
      were also statistically significant differences in PT and PI between male and
      female subjects, while PI was found to increase with age.

PMID- 29017302
TI  - Cervical Pedicle Screw Placement Using Medial Funnel Technique.
AB  - OBJECTIVE: Cervical pedicle screw (CPS) placement is very challenging due to high
      risk of neurovascular complications. We devised a new technique (medial funnel
      technique) to improve the accuracy and feasibility of CPS placement. METHODS: We
      reviewed 28 consecutive patients undergoing CPS instrumentation using the medial
      funnel technique. Their mean age was 51.4 years (range, 30-81 years).
      Preoperative diagnosis included degenerative disease (n=5), trauma (n=22), and
      infection (n=1). Screw perforations were graded with the following criteria:
      grade 0 having no perforation, grade 1 having <25%, grade 2 having 25%-50% and
      grade 3 having >50% of screw diameter. Grades 0 and 1 were considered as correct
      position. The degree of perforation was determined by 2 junior neurosurgeons and
      1 senior neurosurgeon. RESULTS: A total of 88 CPSs were inserted. The rate of
      correct placement was 94.3%; grade 0, 54 screws; grade 1, 29 screws; grade 2, 4
      screws; and grade 3, 1 screw. No neurovascular complications or failure of
      instrumentation occurred. In perforated screws (34 screws), lateral perforations
      were 4 and medial perforations were 30. CONCLUSION: We performed CPS insertion
      using medial funnel technique and achieved 94.3% (83 of 88) of correct placement.
      And it can decrease lateral perforation.

PMID- 29017303
TI  - Single Stage Posterior Approach for Total Resection of Presacral Giant
      Schwannoma: A Technical Case Report.
AB  - The neurogenic tumor of frequent occurrence in the presacral area is a
      schwannoma. Giant presacral schwannoma has a risk for anterior surgical approach
      because of its massive size and proximity to abundant vascularity of presacral
      region. We report a single stage posterior approach for total resection of a
      giant presacral schwannoma. A 40-year-old female patient experienced left buttock
      pain and tingling sensation at left S1 dermatome. Magnetic resonance imaging
      showed that the presacral huge mass at S1-3 level with osseous extension and
      structural remodeling in left sacral ala. The presacral mass was ranging in
      maximum diameter from 8.0 to 8.6 cm. S2 foramen laminectomy was performed to
      expose the mass. The tumor capsule and the root were carefully dissected away.
      The tumor was removed while preserving the capsule by dissecting the plane
      between the inner wall of the capsule and the tumor. The single stage posterior
      approach for presacral giant schwannoma is feasible, and it can be a good
      surgical alternative to prevent pelvic organ or vascular damage and anterior
      approach related dystocia and infertility.

PMID- 29017304
TI  - Hemorrhagic Lumbar Synovial Cyst after Microscopic Discectomy.
AB  - Intraspinal synovial cysts are rare but they are being documented with increasing
      frequency due to improvements in radiological imaging. However, hemorrhage into
      synovial cysts is uncommon, and affected patients may present with acute onset
      radiculopathy. This type of hemorrhage is known to result from rupture of fragile
      neoangiogenic vessels in the cyst wall, due to a traumatic event or anticoagulant
      therapy. Here, the authors present a rare case of hemorrhagic lumbar synovial
      cyst caused by spinal instability after microscopic discectomy. To the best of
      the authors' knowledge, this is the first report of hemorrhagic lumbar synovial
      cyst caused by spinal instability following microscopic discectomy in the absence
      of a traumatic event or anticoagulant therapy. We discuss the pathophysiological
      mechanism of this uncommon entity and provide a review of the literature.

PMID- 29017305
TI  - Spontaneous Epidural Hematoma Associated with Venous Phlebolith in Cervical Spine
      and Possible Pathogenesis.
AB  - Although the etiology of spontaneous spinal epidural hematoma (SSEH) is unclear,
      SSEH is known to be associated with anticoagulants, coagulopathy, vascular
      malformation, hypertension, and pregnancy. However, no report has been issued on
      the relation between SSEH and venous phlebolith. Here, the authors present an
      extremely rare case of SSEH associated with phlebolith in the cervical spine and
      suggest a possible pathogenesis. A 36-year-old man without any relevant medical
      history presented with neck pain and numbness and severe radiating pain on the
      left arm. Magnetic resonance imaging showed epidural hematoma at the C5-7 level,
      and computed tomography revealed a calcified nodule in the left epidural
      hemorrhage at C6 level. During left partial laminectomy, epidural venous plexus,
      and thick epidural hematoma were found, and hematoma removal revealed a white,
      ovoid, smooth, hard mass of diameter 3 mm. Histopathologic examination confirmed
      the mass as a venous phlebolith. The presence of a calcified solitary nodule in
      dorsal epidural space indicates the presence of phlebolith and the risk of SSEH.
      In such cases, the authors recommend spine surgeons should take into
      consideration the possibility of epidural hemorrhage.

PMID- 29017306
TI  - Solitary Osteochondroma Presenting as a Dumbbell Tumor Compressing the Cervical
      Spinal Cord.
AB  - We report a case of a solitary osteochondroma as a dumbbell tumor compressing the
      spinal cord and its surgical strategy. The patient is a 16-year-old female with
      longstanding posterior neck pain and left arm abduction weakness. She was
      examined by plain X-ray, three-dimensional-computed tomography, magnetic
      resonance imaging, and vertebral angiography. The analyses indicated a calcified
      extradural mass compressing the cord in the C3-4 portion extending into the
      neural and vertebral foramen with eroded vertebral body. The tumor was
      successfully excised using a modified combined anterior and posterior approach.
      Histopathologic study of the resected material confirmed the diagnosis. The
      postoperative assessment was followed by clinical and radiologically therapy for
      5 years after surgery. Osteochondroma arises from enchondral bone but it rarely
      involves the spine, especially not as s dumbbell type. In this patient, the tumor
      may have arisen from the neural arch and extended into the extradural and
      extraforaminal space over a long period. We successfully removed the dumbbell
      tumor with a combined anterior oblique and posterior approach. However, further
      observation is essential because of the possibility of recurrence and sarcomatous
      change.

PMID- 29017307
TI  - Incarceration of Spinal Nerve Root through Incidental Durotomy as a Cause of
      Sciatica.
AB  - Incidental durotomies are a frequent complication during spinal surgery.
      Cerebrospinal fluid (CSF) leakage from a dural tear may be visually apparent
      intraoperatively, but occasionally, a tear may not be recognized during the
      procedure. We report our experience in 2 cases of postoperative incarceration of
      nerve root as a cause of sciatica, without CSF leakage intraoperatively. When
      durotomy attributable to surgical manipulation does occur, intraoperative
      identification is mandated. If a patient develops unexplainable postoperative
      pain and neurological deficits after lumbar discectomy, incarceration of nerve
      root should be considered in the differential diagnosis.

PMID- 29017308
TI  - Ganglioneuroma of the Sacrum.
AB  - Presacral ganglioneuromas are extremely rare benign tumors and fewer than 20
      cases have been reported in the literature. Ganglioneuromas are difficult to be
      differentiated preoperatively from tumors such as schwannomas, meningiomas, and
      neurofibromas with imaging modalities. The retroperitoneal approach for resection
      of presacral ganglioneuroma was performed for gross total resection of the tumor.
      Recurrence and malignant transformation of these tumors is rare. Adjuvant
      chemotherapy or radiation therapy is not indicated because of their benign
      nature. We report a case of a 47-year-old woman with a presacral ganglioneuroma.

PMID- 29017309
TI  - Langerhans Cell Histiocytosis of the Thoracic Spine in an Adult.
AB  - We report a case of a 45-year-old man with a complaint of both leg weakness and
      hypoesthesia. Radiological evaluation revealed an osteolytic lesion of the ninth
      thoracic vertebra. The patient underwent posterior corpectomy with total excision
      of the tumor, mesh cage insertion with posterior screw fixation and subsequent
      radiotherapy. Histology confirmed the diagnosis of Langerhans cell histiocytosis
      (LCH). This case report presents the diagnostic work-up, histopathological
      evaluation, and the treatment procedures of rare LCH in the thoracic spine.

PMID- 29017310
TI  - Angiolipoma on the Lumbar Spine.
AB  - Angiolipomas are composed of mature adipose tissue and blood vessels. Spinal
      angiolipomas are rare benign tumors with a good prognosis, and most symptoms are
      due to progressive compression of the spinal cord and root. The treatment of
      choice is total resection without any additional therapy. We report a case of an
      epidural angiolipoma on the lumbar spine in a 69-year-old man with weakness of
      the lower extremities. Lumbar magnetic resonance images revealed a well-enhanced
      epidural mass. He underwent laminectomy, and the tumor was completely removed.
      Pathologic examination confirmed the tumor was an angiolipoma. The patient's
      symptoms gradually improved postoperatively.

PMID- 29017311
TI  - Posterior Epidural Herniation of a Lumbar Disk Fragment at L2-3 That Mimicked an
      Epidural Hematoma.
AB  - Lumbar disk herniation is common. Because of the posterior longitudinal ligament,
      migration usually occurs into the ventral epidural space. Rarely, fragments
      migrate into the dorsal epidural space. A 57-year-old man presented with lower
      back pain and weakness on right hip flexion and right knee flexion. He had lower
      back pain 1 day previously and received a transforaminal epidural block at a
      local hospital. The next day, he reported weakness of the right lower extremity.
      Lumbar spine magnetic resonance imaging revealed a dorsal epidural lesion with
      compression of the thecal sac at L2-3. Initial differential diagnoses included
      epidural hematoma after the block, neoplasm, and a sequestrated disk. Posterior
      lumbar decompression was performed. The lesion was identified intraoperatively as
      a large herniated disk fragment. Posterior epidural herniation of a lumbar disk
      fragment is rare and may be difficult to diagnose preoperatively. It may present
      as a variety of clinical scenarios and, as in this case, may mimic epidural
      hematoma.

PMID- 29017312
TI  - Aortic Injury during Transforaminal Lumbar Interbody Fusion.
AB  - Aortic injury during transforaminal lumbar interbody fusion (TLIF) is a rare but
      severe complication. We experienced aortic injury during TLIF at L3-4 with a 59
      year-old woman diagnosed with an adjacent segment disease at L3-4. Severe
      bleeding occurred during disc space expansion, and the blood pressure dropped to
      60/40 mmHg. The patient's vital sign stabilized after compression with gauze and
      Gelfoam in addition to blood transfusion. The patient was treated with
      endovascular repair using a percutaneous technique after intertransverse fusion
      at L3-4 was completed. She recovered and is being followed-up in the outpatient
      department.

PMID- 29017313
TI  - Posttraumatic Guillain-Barre Syndrome Immediately Following a Traffic Accident.
AB  - Guillain-Barre syndrome (GBS) is an inflammatory demyelinating polyneuropathy
      characterized by areflexic paralysis. Most cases of GBS are preceded by an
      infection, however, posttraumatic GBS has also recently been reported. We report
      a case of posttraumatic GBS immediately following a traffic accident. We think
      this case is of clinical significance for practitioners because of the rare cause
      of a sudden flaccid paralysis following trauma.

PMID- 29017314
TI  - Thyroid Fine-Needle Aspiration Cytology Practice in Korea.
AB  - We reviewed the current status of thyroid fine-needle aspiration cytology (FNAC)
      in Korea. Thyroid aspiration biopsy was first introduced in Korea in 1977.
      Currently, radiologists aspirate the thyroid nodule under the guidance of
      ultrasonography, and cytologic interpretation is only legally approved when a
      cytopathologist makes the diagnosis. In 2008, eight thyroid-related societies
      came together to form the Korean Thyroid Association. The Korean Society for
      Cytopathology and the endocrine pathology study group of the Korean Society for
      Pathologists have been updating the cytologic diagnostic guidelines. The Bethesda
      System for Reporting Thyroid Cytopathology was first introduced in 2009, and has
      been used by up to 94% of institutions by 2016. The average diagnosis rates are
      as follows for each category: I (12.4%), II (57.9%), III (10.4%), IV (2.9%), V
      (3.7%), and VI (12.7%). The malignancy rates in surgical cases are as follows for
      each category: I (28.7%), II (27.8%), III (50.6%), IV (52.3%), V (90.7%), and VI
      (100.0%). Liquid-based cytology has been used since 2010, and it was utilized by
      68% of institutions in 2016. The categorization of thyroid lesions into "atypia
      of undetermined significance" or "follicular lesion of undetermined significance"
      is necessary to draw consensus in our society. Immunocytochemistry for galectin-3
      and BRAF is used. Additionally, a molecular test for BRAF in thyroid FNACs is
      actively used. Core biopsies were performed in only 44% of institutions. Even the
      institutions that perform core biopsies only perform them for less than 3% of all
      FNACs. However, only 5% of institutions performed core biopsies up to three times
      more than FNAC.

PMID- 29017315
TI  - Thyroid Cytology: The Japanese System and Experience at Yamashita Thyroid
      Hospital.
AB  - In Japan, fine-needle aspiration (FNA) cytology is the most important diagnostic
      modality for triaging patients with thyroid nodules. A clinician
      (endocrinologist, endocrine surgeon, or head and neck surgeon) generally performs
      FNA cytology at the outpatient clinic, and ultrasound (US)-guided FNA is
      widespread because US is extremely common and most clinicians are familiar with
      it. Although almost all FNA thyroid samples are examined by certified
      cytopathologists and pathologists, some clinicians assess cytological specimens
      themselves. In Japan, there are two clinical guidelines regarding the management
      of thyroid nodules. One is the General Rules for the Description of Thyroid
      Cancer (GRDTC) published by the Japanese Society of Thyroid Surgery (JSTS) in
      2005, and the other is the national reporting system for thyroid FNA cytology
      published by the Japan Thyroid Association in 2013 (Japanese system). Although
      the Bethesda System for Reporting Thyroid Cytopathology (Bethesda system) is
      rarely used in Japan, both the GRDTC and Japanese system tried to incorporate the
      Bethesda system so that the cytological diagnoses would be compatible with each
      other. The essential point of the Japanese system is stratification of follicular
      neoplasm (FN) into three subgroups based on cytological features in order to
      reduce unnecessary diagnostic thyroidectomy, and this system has been successful
      in stratifying the risk of malignancy in FN patients at several high-volume
      thyroid surgery centers. In Japan, the measurement of thyroglobulin and/or
      calcitonin in FNA needle washings is often used as an adjunct for diagnosis of
      possible cervical lymph node metastasis when FNA cytology is performed.

PMID- 29017316
TI  - Piggyback Rendezvous Cannulation for Endoscopic Metal Stent Conversion of
      Percutaneous Transhepatic Biliary Drainage.

PMID- 29017317
TI  - Novel Multi-isotope Tracer Approach To Test ZnO Nanoparticle and Soluble Zn
      Bioavailability in Joint Soil Exposures.
AB  - Here we use two enriched stable isotopes, 68Znen and 64Znen (>99%), to prepare
      68ZnO nanoparticles (NPs) and soluble 64ZnCl2. The standard LUFA 2.2 test soil
      was dosed with 68ZnO NPs and soluble 64ZnCl2 to 5 mg kg-1 each, plus between 0
      and 95 mg kg-1 of soluble ZnCl2 with a natural isotope composition. After 0, 1,
      3, 6, and 12 months of soil incubation, earthworms (Eisenia andrei) were
      introduced for 72 h exposures. Analyses of soils, pore waters, and earthworm
      tissues using multiple collector inductively coupled plasma mass spectrometry
      allowed the simultaneous measurement of the diagnostic 68Zn/66Zn, 64Zn/66Zn, and
      68Zn/64Zn ratios, from which the three different isotopic forms of Zn were
      quantified. Eisenia andrei was able to regulate Zn body concentrations with no
      difference observed between the different total dosing concentrations. The
      accumulation of labeled Zn by the earthworms showed a direct relationship with
      the proportion of labeled to total Zn in the pore water, which increased with
      longer soil incubation times and decreasing soil pH. The 68Znen/64Znen ratios
      determined for earthworms (1.09 +/- 0.04), soils (1.09 +/- 0.02), and pore waters
      (1.08 +/- 0.02) indicate indistinguishable environmental distribution and uptake
      of the Zn forms, most likely due to rapid dissolution of the ZnO NPs.

PMID- 29017318
TI  - Environmental Aspects of Use of Recycled Carbon Fiber Composites in Automotive
      Applications.
AB  - The high cost and energy intensity of virgin carbon fiber manufacture provides an
      opportunity to recover substantial value from carbon fiber reinforced plastic
      wastes. In this study, we assess the life cycle environmental implications of
      recovering carbon fiber and producing composite materials as substitutes for
      conventional and proposed lightweight materials in automotive applications (e.g.,
      steel, aluminum, virgin carbon fiber). Key parameters for the recycled carbon
      fiber materials, including fiber volume fraction and fiber alignment, are
      investigated to identify beneficial uses of recycled carbon fiber in the
      automotive sector. Recycled carbon fiber components can achieve the lowest life
      cycle environmental impacts of all materials considered, although the actual
      impact is highly dependent on the design criteria (lambda value) of the specific
      component. Low production impacts associated with recycled carbon fiber
      components are observed relative to lightweight competitor materials (e.g.,
      aluminum, virgin carbon fiber reinforced plastic). In addition, recycled carbon
      fiber components have low in-use energy use due to mass reductions and associated
      reduction in mass-induced fuel consumption. The results demonstrate environmental
      feasibility of the CFRP recycling materials, supporting the emerging
      commercialization of CF recycling technologies and identifying significant
      potential market opportunities in the automotive sector.

PMID- 29017319
TI  - A Prototype for Modular Cell Engineering.
AB  - When aiming to produce a target chemical at high yield, titer, and productivity,
      various combinations of genetic parts available to build the target pathway can
      generate a large number of strains for characterization. This engineering
      approach will become increasingly laborious and expensive when seeking to develop
      desirable strains for optimal production of a large space of biochemicals due to
      extensive screening. Our recent theoretical development of modular cell (MODCELL)
      design principles can offer a promising solution for rapid generation of optimal
      strains by coupling a modular cell with exchangeable production modules in a plug
      and-play fashion. In this study, we experimentally validated some design
      properties of MODCELL by demonstrating the following: (i) a modular (chassis)
      cell is required to couple with a production module, a heterologous ethanol
      pathway, as a testbed, (ii) degree of coupling between the modular cell and
      production modules can be modulated to enhance growth and product synthesis,
      (iii) a modular cell can be used as a host to select an optimal pyruvate
      decarboxylase (PDC) of the ethanol production module and to help identify a
      hypothetical PDC protein, and (iv) adaptive laboratory evolution based on growth
      selection of the modular cell can enhance growth and product synthesis rates. We
      envision that the MODCELL design provides a powerful prototype for modular cell
      engineering to rapidly create optimal strains for synthesis of a large space of
      biochemicals.

PMID- 29017320
TI  - Factors Controlling the Reactivity and Chemoselectivity of Resonance Destabilized
      Amides in Ni-Catalyzed Decarbonylative and Nondecarbonylative Suzuki-Miyaura
      Coupling.
AB  - N-Glutarimide amides have recently emerged as an exceptional group of compounds
      with unusually high reactivity in amide C-N bond activation. To understand the
      key factors that control the remarkable reactivity of these resonance
      destabilized amides, we explored the Ni-catalyzed decarbonylative and
      nondecarbonylative Suzuki-Miyaura coupling with N-glutarimide amides through
      density functional theory calculations. Two leading effects are responsible for
      the C-N cleavage activity of N-glutarimide amides, the coordinating N
      substituents and the geometric twisting. The carbonyl substituent of the N
      glutarimide amides provides crucial nickel-oxygen interaction, which essentially
      acts as a directing group to facilitate the formation of the reactive
      intermediate for the amide C-N bond cleavage. The geometric twisting weakens the
      resonance stability by removing the acyl-nitrogen conjugation, which lowers the
      energy penalty for the C-N bond stretch during oxidative addition. For the
      chemoselectivity of decarbonylation versus carbonyl retention, we found that the
      C-C reductive elimination for ketone formation is kinetically faster than that
      for biaryl formation, while ketone is thermodynamically less stable with respect
      to the decarbonylated biaryls. The computations also suggest that the nickel
      catalyst is able to promote the decarbonylation of biaryl ketones via an
      unexpected C-C bond activation.

PMID- 29017321
TI  - Terminal Electron-Proton Transfer Dynamics in the Quinone Reduction of
      Respiratory Complex I.
AB  - Complex I functions as a redox-driven proton pump in aerobic respiratory chains.
      By reducing quinone (Q), complex I employs the free energy released in the
      process to thermodynamically drive proton pumping across its membrane domain. The
      initial Q reduction step plays a central role in activating the proton pumping
      machinery. In order to probe the energetics, dynamics, and molecular mechanism
      for the proton-coupled electron transfer process linked to the Q reduction, we
      employ here multiscale quantum and classical molecular simulations. We identify
      that both ubiquinone (UQ) and menaquinone (MQ) can form stacking and hydrogen
      bonded interactions with the conserved Q-binding-site residue His-38 and that
      conformational changes between these binding modes modulate the Q redox
      potentials and the rate of electron transfer (eT) from the terminal N2 iron
      sulfur center. We further observe that, while the transient formation of
      semiquinone is not proton-coupled, the second eT process couples to a
      semiconcerted proton uptake from conserved tyrosine (Tyr-87) and histidine (His
      38) residues within the active site. Our calculations indicate that both UQ and
      MQ have low redox potentials around -260 and -230 mV, respectively, in the Q
      binding site, respectively, suggesting that release of the Q toward the membrane
      is coupled to an energy transduction step that could thermodynamically drive
      proton pumping in complex I.

PMID- 29017322
TI  - Fabrication and Properties of a Free-Standing Two-Dimensional Titania.
AB  - The synthesis of free-standing two-dimensional titania (2-D TiO2) with a reduced
      band gap presents complex challenges to synthetic chemists. Here, we report a
      free-standing 2-D TiO2 sheet synthesized via a one-step solvothermal methodology,
      with a measured optical onset at ~1.84 eV. Using first-principles calculations in
      combination with experiment, we propose that the as-formed 2-D TiO2 sheets are
      layers of the lepidocrocite TiO2 structure, but with large nonuniform strains
      consistent with its crumpled morphology. These strains cause a significant change
      in the quasiparticle band structure and optical absorption spectra, resulting in
      large absorption in the visible-light region. This narrow band gap 2-D TiO2 can
      catalyze the formation of singlet oxygen and the degradation of dye pollutants
      with low-energy photons of solar light. Our work demonstrates that lattice
      strains intrinsic to 2-D materials, especially its crumpled, free-standing forms,
      can result in new and useful properties.

PMID- 29017323
TI  - DFT and AFIR Study on the Mechanism and the Origin of Enantioselectivity in Iron
      Catalyzed Cross-Coupling Reactions.
AB  - The mechanism of the full catalytic cycle for Fe-chiral-bisphosphine-catalyzed
      cross-coupling reaction between alkyl halides and Grignard reagents (Nakamura and
      co-workers, J. Am. Chem. Soc. 2015, 137, 7128) was rationalized by using density
      functional theory (DFT) and multicomponent artificial force-induced reaction (MC
      AFIR) methods. The computed mechanism consists of (a) C-Cl activation, (b)
      transmetalation, (c) C-Fe bond formation, and (d) C-C bond formation through
      reductive elimination. Our survey on the prereactant complexes suggested that
      formation of FeII(BenzP*)Ph2 and FeI(BenzP*)Ph complexes are thermodynamically
      feasible. FeI(BenzP*)Cl complex is the active intermediate for C-Cl activation.
      FeII(BenzP*)Ph2 complex can be formed if the concentration of Grignard reagent is
      high. However, it leads to biphenyl (byproduct) instead of the cross-coupling
      product. This explains why slow addition of Grignard reagent is critical for the
      cross-coupling reaction. The MC-AFIR method was used for systematic determination
      of transition states for C-Fe bond formation and C-C bond formation starting from
      the key intermediate FeII(BenzP*)PhCl. According to our detailed analysis, C-C
      bond formation is the selectivity-determining step. The computed enantiomeric
      ratio of 95:5 is in good agreement with the experimental ratio (90:10). Energy
      decomposition analysis suggested that the origin of the enantioselectivity is the
      deformation of Ph-ligand in Fe-complex, which is induced by the bulky tert-butyl
      group of BenzP* ligand. Our study provides important mechanistic insights for the
      cross-coupling reaction between alkyl halides and Grignard reagents and guides
      the design of efficient Fe-based catalysts for cross-coupling reactions.

PMID- 29017324
TI  - Molecular Dynamics Simulations of Ceramide and Ceramide-Phosphatidylcholine
      Bilayers.
AB  - Recent studies in lipid raft formation and stratum corneum permeability have
      focused on the role of ceramides (CER). In this study, we use the all-atom
      CHARMM36 (C36) force field to simulate bilayers using N-palmitoylsphingosine
      (CER16) or alpha-hydroxy-N-stearoyl phytosphingosine (CER[AP]) in 1,2-dimyristoyl
      sn-glycero-3-phosphocholine (DMPC) or 1-palmitoyl-2-oleoylphosphatidylcholine
      (POPC), which serve as general membrane models. Conditions are replicated from
      experimental studies for comparison purposes, and concentration (XCER) is varied
      to probe the effect of CER on these systems. Comparisons with experiment based on
      deuterium order parameters and bilayer thickness demonstrate good agreement, thus
      supporting further use of the C36 force field. CER concentration is shown to have
      a profound effect on nearly all membrane properties including surface area per
      lipid, chain order and tilt, area compressibility moduli, bilayer thickness,
      hydrogen bonding, and lipid clustering. Hydrogen bonding in particular can
      significantly affect other membrane properties and can even encourage transition
      to a gel phase. Despite CER's tendency to condense the membrane, an expansion of
      CER lipids with increasing XCER is possible depending on how the balance between
      various hydrogen-bond pairs and lipid clustering is perturbed. Based on gel phase
      transitions, support is given for phytosphingosine's role as a hydrogen-bond
      bridge between sphingosine ordered domains in the stratum corneum.

PMID- 29017325
TI  - Photocatalytic Active Mesoporous Carbon/ZnO Hybrid Materials from Block Copolymer
      Tethered ZnO Nanocrystals.
AB  - Severe water pollution issues present an important contemporary challenge that
      drives the development and advancement of efficient and environmentally benign
      photocatalysts that enable the degradation of pollutants upon visible light
      irradiation. One example is zinc oxide/carbon (ZnO/C) hybrid materials that have
      been shown to be effective photocatalysts. To maximize the effectiveness of ZnO/C
      hybrids, materials with high accessible surface area of ZnO are required. Here, a
      novel strategy is presented to enable the synthesis of fine dispersions of ZnO
      nanoparticles within a porous carbon matrix. The synthesis entails the grafting
      of ZnO nanparticles with polystyrene-b-poly(styrene-co-acrylonitrile) (PS-b-PSAN)
      block copolymer and subsequent pyrolysis of the material under inert gas (N2)
      atmosphere. During the pyrolysis process, the PS block effectively prevents
      agglomeration of ZnO particles, thus resulting in a fine dispersion of ZnO
      nanocrystals within a prorous C matrix. Materials are found to exhibit a dye
      adsorption capacity of 125 mg g-1 (from a methylene blue aqueous solution with a
      concentration of 305 mg L-1) and dye degradation rate constant of 0.021 min-1.
      The significant increase of effective surface area and degradation efficacy (as
      compared to ZnO/C synthesized by the pyrolysis of binary PSAN/ZnO blends) is
      rationalized as a consequence of the increased porosity that promotes dye
      adsorption and transport within the hybrid material.

PMID- 29017326
TI  - Mechanism of Nakamura's Bisphosphine-Iron-Catalyzed Asymmetric C(sp2)-C(sp3)
      Cross-Coupling Reaction: The Role of Spin in Controlling Arylation Pathways.
AB  - Quantum mechanical calculations are employed to investigate the mechanism and
      origin of stereoinduction in asymmetric iron-catalyzed C(sp2)-C(sp3) cross
      coupling reaction between Grignard reagents and alpha-chloroesters. A coherent
      mechanistic picture of this transformation is revealed. These results have broad
      implications for understanding the mechanisms of iron-catalyzed cross-coupling
      reactions and rational design of novel iron-based catalysts for asymmetric
      transformations.

PMID- 29017327
TI  - Enhancing the Bactericidal Efficacy of Nanostructured Multifunctional Surface
      Using an Ultrathin Metal Coating.
AB  - Insects and plants exhibit bactericidal behavior through nanostructures, which
      leads to physical contact killing that does not require antibiotics or chemicals.
      Also, certain metallic ions (e.g., Ag+ and Cu2+) are well-known to kill bacteria
      by disrupting their cellular functionalities. The aim of this study is to explore
      the improvement in bactericidal activity by combining extreme physical structure
      with surface chemistry. We have fabricated tall (8-9 MUm high) nanostructures on
      silicon surfaces (NSS) having sharp tips (35-110 nm) using a single-step,
      maskless deep reactive ion etching technique inspired by dragonfly wing.
      Bactericidal efficacy of the nanostructured surfaces coated with a thin layer of
      silver (NSS_Ag) or copper (NSS_Cu) was measured quantitatively using standard
      viability plate-count method and flow cytometry. NSS_Cu surfaces kill bacteria
      very efficiently (killing 97% within 30 min) when compared to the uncoated NSS.
      This can be attributed to the addition of a surface chemistry to the
      nanostructures. The antibacterial activity of NSS_Cu is further indicated by the
      morphological differences of the dying/dead bacteria observed in the SEM images.
      The nanostructured surfaces demonstrate excellent superhydrophobic behavior, even
      with an ultrathin layer of metal (Ag/Cu) coating. The nanostructured surfaces
      exhibit static contact angle greater than 150 degrees  and contact hysteresis
      less than 10 degrees . Moreover, reflectance is found to be <1% (for NSS_Cu <
      0.5%) for all the nanostructured surfaces in the wavelength range 250-800 nm. The
      results obtained suggest that the fabricated nanostructured surfaces are
      multifunctional and can be used in various practical applications.

PMID- 29017328
TI  - The Tolerome: A Database of Transcriptome-Level Contributions to Diverse
      Escherichia coli Resistance and Tolerance Phenotypes.
AB  - Tolerance and resistance are complex biological phenotypes that are desirable
      bioengineering goals for those seeking to design industrial strains or prevent
      the spread of antibiotic resistance. Over decades of research, a wealth of
      information has been generated to attempt to decode a molecular basis for
      tolerance, but to fully achieve the goal of engineering tolerance, researchers
      must be able to easily learn from a variety of data sources. To this end, we here
      describe a resource designed to enable scrutiny of diverse tolerance phenotypes.
      We have curated hundreds of gene expression studies exploring the response of
      Escherichia coli to chemical and environmental perturbations, from antibiotics to
      biofuels and solvents and more. Overall, our efforts give rise to a database
      encompassing more than 56 000 gene expression changes across 89 different stress
      conditions. This resource is designed for compatibility with the Resistome
      database, which includes more than 5000 strains with mutations conferring
      resistance or sensitivity but no transcriptomic data. Thus, the work here results
      in the first combined resource specialized to tolerance and resistance in E. coli
      that supports investigations across genomic, transcriptomic, and phenotypic
      levels. We leverage the database to identify promising bioengineering targets by
      searching globally across multiple stress conditions as well as by narrowing the
      focus to fewer conditions of interest, such as biofuel stress and antibiotic
      stress. We discuss some of the most frequently differentially expressed or
      coexpressed genes, and predict which transcription factors and sigma factors most
      likely contribute to gene expression profiles in a wide array of conditions. We
      also compare profiles from sensitive and resistant strains, gaining knowledge of
      how responses differ per overrepresented gene ontology terms. Finally, we search
      for genes that are frequently differentially expressed but not mutated, with the
      expectation that these may present interesting targets for future engineering
      efforts. The curated data presented here is publicly available, and should be
      advantageous to those studying a variety of bacterial tolerance phenotypes.

PMID- 29017329
TI  - Modulation of n-Type Units in Bipolar Host Materials toward High-Performance
      Phosphorescent OLEDs.
AB  - 9'-Pyridinyl-9'H-9,3':6',9"-tercarbazole (PyCz) is a bipolar host material in
      phosphorescent organic light-emitting diodes (PhOLEDs). A second n-type unit,
      either pyridine or diphenylphosphine dioxide (DPPO), is introduced onto the
      pyridine ring of PyCz at para- or metasite to design and prepare four novel "dual
      n-type unit bipolar host" materials m-BPyCz, p-BPyCz, m-POPyCz, and p-POPyCz. The
      incorporation of the second n-type unit pulls down the lowest unoccupied
      molecular orbitals and facilitates electron injection and transportation,
      resulting in better charge-balancing ability. As a result, these dual n-type unit
      bipolar hosts exhibit higher efficiencies and slower efficiency roll-off in their
      blue and green PhOLEDs. In particular, m-POPyCz containing a bulky DPPO as the
      second n-type unit with a metalinking possesses the best charge-balancing state
      and generates a maximum external quantum efficiency (etaext) of 27.0%
      (corresponding to a current efficiency of 51.9 cd A-1 and a power efficiency of
      46.5 lm W-1) in its sky-blue device and still remained at a high etaext of 23.6%
      even at the practical brightness of 1000 cd m-2. These results clearly
      demonstrate that the "dual n-type unit bipolar hosts" with an optimized
      substitution position and steric effect is a new and effective type of host
      materials for high-performance OLEDs.

PMID- 29017331
TI  - Distinct prognostic roles of HSPB1 expression in non-small cell lung cancer.
AB  - Lung cancer is the leading cause of cancer morbidity and mortality around world.
      Heat shock protein beta-1 (HSPB1) expression is aberrantly increased in non-small
      cell lung cancer (NSCLC) patients. However, the roles of HSPB1 expression in the
      prognosis of NSCLC are still elusive. In this study, we investigated the
      prognostic roles of HSPB1 in NSCLC by using "The Kaplan-Meier plotter" (KM
      plotter) database. Our data indicated that HSPB1 mRNA low expression was
      correlated to better overall survival (OS) for all NSCLC patients, hazard ratio
      (HR) 1.41 (1.24-1.61), p=1.1e-7, and better OS in lung adenocarcinoma (LUAD)
      patients, HR 1.81 (1.42-2.32), p=1.5e-06, but not in lung squamous cell carcinoma
      (LUSC) patients, HR 1.21 (0.94-1.55), p=0.14. In addition, mRNA low expression of
      HSPB1 is also significantly associated with better OS of NSCLC patients in
      different smoking status, in different chemotherapy status, in clinical stage I
      et II, as well as patients with successful surgery treatment. Our results
      indicated that HSPB1 expression may have distinct prognostic values in NSCLC
      patients, and may provide an effective clinical strategy to accurately predict
      the prognosis of NSCLC patients.

PMID- 29017332
TI  - Shared decision making in mental health: the importance for current clinical
      practice.
AB  - OBJECTIVES: We reviewed the literature on shared decision making (regarding
      treatments in psychiatry), with a view to informing our understanding of the
      decision making process and the barriers that exist in clinical practice.
      METHODS: Narrative review of published English-language articles. RESULTS: After
      culling, 18 relevant articles were included. Themes identified included models of
      psychiatric care, benefits for patients, and barriers. There is a paucity of
      published studies specifically related to antipsychotic medications. CONCLUSIONS:
      Shared decision making is a central part of the recovery paradigm and is of
      increasing importance in mental health service delivery. The field needs to
      better understand the basis on which decisions are reached regarding psychiatric
      treatments. Discrete choice experiments might be useful to inform the development
      of tools to assist shared decision making in psychiatry.

PMID- 29017333
TI  - Predicting Sexual Revictimization in Childhood and Adolescence: A Longitudinal
      Examination Using Ecological Systems Theory.
AB  - A substantial proportion of sexual abuse victims report repeat sexual
      victimization within childhood or adolescence; however, there is limited
      understanding of factors contributing to revictimization for youth. Thus, the
      present study examined predictors of sexual revictimization prior to adulthood
      using ecological systems theory. Records of 1,915 youth presenting to a Child
      Advocacy Center (CAC) were reviewed to identify individual, familial, and
      community factors as well as initial abuse characteristics associated with risk
      for revictimization. Results showed that 11.1% of youth re-presented to the CAC
      for sexual revictimization. At the individual level, younger children, girls,
      ethnoracial minority youth, and those with an identified mental health problem
      were most likely to experience revictimization. Interpersonal factors that
      increased vulnerability included the presence of a noncaregiving adult in the
      home, being in mental health treatment, and domestic violence in the family.
      Community-level factors did not predict revictimization. When factors at all
      levels were examined in conjunction, however, only individual-level factors
      significantly predicted the risk for revictimization. Findings from this study
      provide valuable information for CACs when assessing risk for re-report of sexual
      abuse and add to the field's understanding of revictimization within childhood.

PMID- 29017334
TI  - Brexpiprazole: a new leaf on the partial dopamine agonist branch.
AB  - OBJECTIVES: Brexpiprazole is a new dopamine partial agonist antipsychotic in the
      same class as aripiprazole. This paper will briefly review brexpiprazole and
      compare it with aripiprazole. CONCLUSIONS: Brexpiprazole and aripiprazole are
      both partial agonists at dopamine D2, and serotonin 5-HT1A and antagonists at
      serotonin 5-HT2A and noradrenergic alpha1B receptors. However, the two drugs are
      significantly different in potencies at various receptors; neurochemical profiles
      predict that brexpiprazole may be comparable with aripiprazole in its
      antipsychotic efficacy but may cause less akathisia, extrapyramidal side effects
      (EPS) and activation. In pivotal trials brexpiprazole demonstrated antipsychotic
      efficacy in short and long-term studies; it was also found to be an effective
      adjunct in patients with major depression resistant to antidepressants. Akathisia
      can occur early in treatment with brexpiprazole, as can minor weight gain and
      prolactin elevation. Indirect data extrapolations from pivotal studies suggest
      that brexpiprazole and aripiprazole have comparable efficacy but brexpiprazole
      may cause less akathisia. Like aripiprazole, brexpiprazole has been approved in
      the USA for use in schizophrenia and antidepressant-resistant depression.
      Although much more clinical experience is needed, brexpiprazole appears to be
      distinct from aripiprazole and a promising new 'metabolically-friendly'
      antipsychotic option for treatment of psychoses and mood disorders.

PMID- 29017335
TI  - Oxytocin Levels in Community-Collected Saliva Samples Transported by Dry Versus
      Wet Ice.
AB  - Oxytocin (OT), a neuropeptide produced primarily in the hypothalamus, is
      associated with both critical physiological and psychological processes,
      particularly stress and feelings of affiliation. Increasingly, researchers are
      seeking ways to reliably incorporate OT as an outcome biomarker in clinical
      research. Previously, OT levels were measured in plasma or urine. Recently,
      researchers have measured this biomarker in saliva, particularly when conducting
      research in clinical and community settings. In spite of increased interest in
      the use of salivary OT in clinical research, procedures for handling, transport,
      and analysis of specimens vary. It is not known if significant OT protein
      degradation occurs if samples are initially transported on wet ice before being
      frozen. The aim of this study is to evaluate the effect of transport media (wet
      vs. dry ice) on OT levels derived from saliva collected from 12 postpartum women
      residing in the community. Saliva collected from each participant was divided
      between two microcentrifuge tubes (MIDSCI, Valley Park, MO), one placed on wet
      ice and one on dry ice for transport from the participant's home to the
      laboratory freezer. Time from collection to storage freezer was recorded.
      Laboratory personnel, blinded to method of transport, batch processed the
      samples. No significant differences in OT levels were found by transport method.
      Despite large interperson variations in OT levels, there were negligible
      intraperson variations. Although further research is required to identify factors
      (including transport time) related to interperson variation, this study supports
      the use of wet ice as a means of transporting salivary OT specimens in community
      based research.

PMID- 29017337
TI  - Promoting Face-to-Face Dialogue for Community Engagement in a Digital Age.
AB  - Background Health researchers in urban centers recognize the need to engage with
      inner-city community-based organizations. Funding for face-to-face engagement is
      often limited because most work done by agencies and academics now focuses on the
      use of digital technology. Purpose This article presents reflections from a grant
      project aimed at establishing community engagement between academic health
      researchers and interdisciplinary inner-city community health and social service
      providers. Method This study utilized a community-based participatory action
      approach. This study included a 1-day collaborative meeting to promote academic
      agency engagement. During this meeting, the research participants brainstormed
      research priorities and used colored stickers to rank them. The research team met
      the following day to debrief the meeting and to begin analyzing the data
      together. Results The findings from this project have stimulated dialogue among
      the agency partners and project team researchers with respect to current
      collaborations, services provided, and research priorities. Although digital or
      virtual meetings have their place, fostering community engagement through a face
      to-face meeting proved invaluable to the participants. Conclusions The success of
      this Canadian Institutes of Health Research-funded project demonstrates the value
      of academic-agency partnership, the positive aspects of gathering community, and
      engagement in better meeting the research needs of inner-city organizations.

PMID- 29017336
TI  - Increase in Oxytocin From Skin-to-Skin Contact Enhances Development of Parent
      Infant Relationship.
AB  - OBJECTIVE: To examine changes that occur in infant and parent salivary oxytocin
      (OT) and salivary cortisol (SC) levels during skin-to-skin contact (SSC) and
      whether SSC alleviates parental stress and anxiety while also supporting mother
      father-infant relationships. METHODS: This randomized crossover study was
      conducted in the neonatal intensive care unit (NICU) with a sample of 28 stable
      preterm infants and their parents. Saliva samples were collected from infants,
      mothers, and fathers on Days 1 and 2 (1/parent) for OT and cortisol measurement
      pre-SSC, during a 60-min SSC session, and a 45-min post-SSC. Parental anxiety was
      measured at the same time points. Parent-infant interaction was examined prior to
      discharge on Day 3 via video for synchrony and responsiveness using Dyadic
      Mutuality Coding. RESULTS: Salivary OT levels increased significantly during SSC
      for mothers ( p < .001), fathers ( p < .002), and infants ( p < .002). Infant SC
      levels decreased significantly ( p < .001) during SSC as compared to before and
      after SSC. Parent anxiety scores were significantly related to parent OT and SC
      levels. Parents with higher OT levels exhibited more synchrony and responsiveness
      ( p < .001) in their infant interactions. CONCLUSION: This study addresses a gap
      in understanding the mechanisms linking parent-infant contact to biobehavioral
      responses. SSC activated OT release and decreased infant SC levels. Facilitation
      of SSC may be an effective intervention to reduce parent and infant stress in the
      NICU. Findings advance the exploration of OT as a potential moderator for
      improving responsiveness and synchrony in parent-infant interactions.

PMID- 29017353
TI  - Maternal and child nutrition in rural Chhattisgarh: the role of health beliefs
      and practices.
AB  - From research in central Chhattisgarh, this paper interprets the bearing that
      healthcare beliefs and practices may have in shaping maternal and child nutrition
      both in the light of biomedical recommendations and within the context and
      constraints of a rural village setting. It contends that health beliefs and
      practices that are at variance from biomedical recommendations appear to have few
      consequences for gestational nutrition and for child health in relation to
      pregnancy. In the postpartum however, health ideas at variance from biomedical
      recommendations appear to have an important bearing on maternal nutrition and
      infant feeding, and may put mothers and children at risk of nutritional
      deficiency. Maternal 'eating down' following a surgical procedure such as a
      caesarean delivery or tubectomy is especially noteworthy, since food intake
      quantity is reduced over an extended time frame. While caring practices are
      influenced by cultural formulations, they also reflect, perhaps, adaptations to
      health risks.

PMID- 29017356
TI  - Antimicrobial activity of Austroeupatorium inulaefolium (H.B.K.) against
      intracellular and extracellular organisms.
AB  - The antimicrobial activity of Austroeupatorium inulaefolium (H.B.K.) essential
      oil was studied in different pathogens species and its cytotoxicity activity was
      determinated on different cellular lines. Despite the good antibacterial activity
      of A. inulaefolium, it has been cytotoxic at low concentrations. Consequently it
      might be interesting to determine the antimicrobial activity and cytotoxicity of
      the major compounds of this essential oil.

PMID- 29017354
TI  - Persistent SIRS and acute fluid collections are associated with increased CT
      scanning in acute interstitial pancreatitis.
AB  - BACKGROUND: The use of computed tomography (CT) in acute pancreatitis (AP)
      continues to increase in parallel with the increasing use of diagnostic imaging
      in clinical medicine. AIM: To determine the factors associated with obtaining >1
      CT scan in acute interstitial pancreatitis (AIP). METHODS: Demographic and
      clinical data of all adult patients admitted between 1/2010 and 1/2015 with AP
      (AP) were evaluated. Only patients with a CT severity index (CTSI) <= 3 on a CT
      obtained within 48 h of presentation were included. RESULTS: A total of 229
      patients were included, of whom 206 (90%) had a single CT and 23 (10%) had >1 CT
      during the first week of hospitalization. Patients undergoing >1 CT had
      significantly higher rates of acute fluid collection (AFC), persistent SIRS,
      opioid use >=4 days, and persistent organ failure compared to those undergoing 1
      CT (p < .05 for all). On multivariable analysis, only persistent SIRS (OR = 3.6,
      95% CI 1.4-9.6, p = .01) and an AFC on initial CT (OR = 3.5, 95% CI 1.4-9, p =
      .009) were independently associated with obtaining >1 CT. CONCLUSION: An AFC on
      initial CT and persistent SIRS are associated with increased CT imaging in AIP
      patients. However, these additional CT scans did not change clinical management.

PMID- 29017358
TI  - Is there evidence for the added value and correct use of manual and automatically
      switching multimemory hearing devices? A scoping review.
AB  - OBJECTIVES: To review literature on the use of manual and automatically switching
      multimemory devices by hearing aid and CI recipients, and to investigate if
      recipients appreciate and adequately use the ability to switch between programmes
      in various listening environments. DESIGN: Literature was searched using PubMed,
      Embase and ISI/Web of Science. Additional studies were identified by screening
      reference and citation lists, and by contacting experts. STUDY SAMPLE: The search
      yielded 1109 records that were screened on title and abstract. This resulted in
      the full-text assessment of 37 articles. RESULTS: Sixteen articles reported on
      the use of multiple programmes for various listening environments, three articles
      reported on the use of an automatic switching mode. All studies reported on
      hearing aid recipients only, no study with CI recipients fulfilled the selection
      criteria. CONCLUSIONS: Despite the high number of manual and automatically
      switching multimemory devices sold each year, there are remarkably few studies
      about the use of multiple programmes or automatic switching modes for various
      listening environments. No studies were found that examined the accuracy of the
      use of programmes for specific listening environments. An automatic switching
      device might be a solution if recipients are not able, or willing, to switch
      manually between programmes.

PMID- 29017357
TI  - Automated hexahedral meshing of knee cartilage structures - application to data
      from the osteoarthritis initiative.
AB  - We propose a fully automated methodology for hexahedral meshing of patient
      specific structures of the human knee obtained from magnetic resonance images,
      i.e. femoral/tibial cartilages and menisci. We select eight patients from the
      Osteoarthritis Initiative and validate our methodology using MATLAB on a laptop
      computer. We obtain the patient-specific meshes in an average of three minutes,
      while faithfully representing the geometries with well-shaped elements. We hope
      to provide a fundamentally different means to test hypotheses on the mechanisms
      of disease progression by integrating our patient-specific FE meshes with data
      from individual patients. Download both our meshes and software at
      http://im.engr.uconn.edu/downloads.php .

PMID- 29017359
TI  - Antenatal scoring system in predicting the success of planned vaginal birth
      following one previous caesarean section.
AB  - This was a prospective observational study to determine the predictive factors
      for a successful vaginal birth after caesarean section (VBAC) and to develop a
      relevant antenatal scoring system. Patients with one previous caesarean section
      were included in this study. All data including maternal demographics, obstetric
      history, pregnancy progress and outcomes were collected and analysed. A total of
      142 out of the 186 women (76.3%) had successful VBAC. History of previous vaginal
      delivery and non-recurrent indications for previous caesarean section were the
      significant predictive factors for a successful VBAC. Five variables for our
      scoring tool were selected. By using a proposed mean score of 4 out of 7, the
      scoring system had a sensitivity of 81.0%, specificity of 52.3% and a positive
      predictive value of 84.6%. VBAC antenatal scoring system was potentially a useful
      predictive tool in antenatal counselling. Impact statement What is already known
      on this subject: Planned vaginal birth after caesarean section (VBAC) is an
      important strategy to limit the overall caesarean section rate, which is related
      to maternal morbidities. However, trial of vaginal delivery does involve
      potential complications including scar dehiscence, postpartum haemorrhage and
      emergency hysterectomy. What the results of this study add: Clinical predictors
      of a successful VBAC include non-recurrent indications for the previous caesarean
      section, previous vaginal delivery, spontaneous onset of labour and birthweight
      less than 4kg. There were multiple screening tools developed to predict the
      likelihood of successful VBAC. These scoring systems involved various variables
      such as age, ethnicity, Bishop's score and previous caesarean indication. We had
      prospectively developed an antenatal scoring system based on five variables. Our
      result showed that patient with a score of four and above will have around 85%
      chance of successful VBAC. What the implications are of these findings for
      clinical practice and/or further research: We have also found that, estimated
      foetal weight based on ultrasound scan is a potential predictor for successful
      VBAC. This simple scoring method will be useful in-patient counselling regarding
      mode of delivery after one previous caesarean section. A multicentre study
      involving large cohort of patients is ideal to validate our scoring system.

PMID- 29017360
TI  - Cognitive emotion regulation strategies and mental health problems in war
      affected youth in Northern Uganda: findings from the WAYS study.
AB  - BACKGROUND: Cognitive emotion regulation strategies (CERS) have been shown to
      moderate the influence of War Experiences (WE) on mental health problems. AIMS:
      This study assessed the influence of WE and use of specific CERS on mental health
      problems among war-affected youth in Northern Uganda. METHODS: Five hundred and
      thirty-nine participants in an ongoing war-affected youth study (WAYS) were
      assessed by locally developed measures. CERS were measured by Cognitive Emotion
      Regulation Questionnaire (CERQ). Multiple regressions were used to assess
      independent effects of gender, WE, and CERS on mental problems and their
      potential interaction. RESULTS: Gender, WE and all CERS except positive
      refocussing and reappraisal had significant independent main effects on symptoms
      of depression while only WE, self-blame and blaming others had significant main
      effects on conduct problems. The interaction terms of WE and coping strategies of
      rumination, catastrophizing, and self-blame significantly predicted symptoms of
      depression/anxiety while only the interaction between WE and blaming others
      predicted conduct problems. In contrast, putting into perspective and planning
      negatively predicted symptoms of depression/anxiety. CONCLUSIONS: Interventions
      to reduce mental health problems should target coping strategies, especially
      adaptive strategies to youth in many post-conflict settings in Africa.

PMID- 29017362
TI  - Association between uncoupling protein 2, adiponectin and resting energy
      expenditure in obese women with normal and low resting energy expenditure.
AB  - Obesity is recognized as the most prevalent metabolic disease worldwide.
      Decreases in energy expenditure may increase risk of obesity. One of the key
      regulators of energy balance is uncoupling protein2 (UCP2), a transporter protein
      presents in mitochondrial inner membrane. Moreover, adiponectin is the most
      abundant adipocytokine, it may play a role in energy metabolism and gene
      expression of UCP2. The aim of this study was to investigate potential
      associations between the level of uncoupling protein 2 and adiponectin and their
      relationship with REE (Resting Energy Expenditure) in obese women with normal and
      low resting energy expenditure. A total of 49 subjects (women, 25-50 years old),
      were included in current study, 16 subjects with BMI > 30 and low resting energy
      expenditure, 17 subjects with BMI > 30 and normal resting energy expenditure and
      16 non-obese subjects as a control group. Anthropometric, body composition
      parameters and resting energy expenditure were measured. Plasma adiponectin, UCP2
      protein and total protein in PBMC were determined. Measured resting energy
      expenditure in obese subjects with low REE was significantly lower than other
      groups. Plasma adiponectin in the obese subjects with low REE was significantly
      lower compared to normal weight group. There was a significant relationship
      between 'UCP2 protein/Total protein' ratio and plasma adiponectin in obese group
      with low REE and in three groups when we pooled. There was a significant
      association between REE and plasma adiponectin in three groups when we pooled.
      There was a significant association between plasma adiponectin and REE. Moreover,
      there was a significant relationship between UCP2 and REE.

PMID- 29017361
TI  - Haptic-assistive technologies for audition and vision sensory disabilities.
AB  - PURPOSE: The aim of this review is to analyze haptic sensory substitution
      technologies for deaf, blind and deaf-blind individuals. METHOD: The literature
      search has been performed in Scopus, PubMed and Google Scholar databases using
      selected keywords, analyzing studies from 1960s to present. Search on databases
      for scientific publications has been accompanied by web search for commercial
      devices. Results have been classified by sensory disability and functionality,
      and analyzed by assistive technology. Complementary analyses have also been
      carried out on websites of public international agencies, such as the World
      Health Organization (WHO), and of associations representing sensory disabled
      persons. RESULTS: The reviewed literature provides evidences that sensory
      substitution aids are able to mitigate in part the deficits in language learning,
      communication and navigation for deaf, blind and deaf-blind individuals, and that
      the tactile sense can be a means of communication to provide some kind of
      information to sensory disabled individuals. CONCLUSIONS: A lack of acceptance
      emerged from the discussion of capabilities and limitations of haptic assistive
      technologies. Future researches shall go towards miniaturized, custom-designed
      and low-cost haptic interfaces and integration with personal devices such as
      smartphones for a major diffusion of sensory aids among disabled. Implications
      for rehabilitation Systematic review of state of the art of haptic assistive
      technologies for vision and audition sensory disabilities. Sensory substitution
      systems for visual and hearing disabilities have a central role in the
      transmission of information for patients with sensory impairments, enabling users
      to interact with the not disabled community in daily activities. Visual and
      auditory inputs are converted in haptic feedback via different actuation
      technologies. The information is presented in the form of static or dynamic
      stimulation of the skin. Their effectiveness and ease of use make haptic sensory
      substitution systems suitable for patients with different levels of disabilities.
      They constitute a cheaper and less invasive alternative to implantable partial
      sensory restitution systems. Future researches are oriented towards the
      optimization of the stimulation parameters together with the development of
      miniaturized, custom-designed and low-cost aids operating in synergy in networks,
      aiming to increase patients' acceptability of these technologies.

PMID- 29017363
TI  - A survey on the use of topical steroids in patients treated for lichen sclerosus
      associated vulval squamous cell carcinoma.
AB  - Evidence suggests that lichen sclerosus (LS) is the primary aetiological factor
      for local vulval recurrence (LVR) in vulval squamous cell carcinoma (VSCC). The
      long-term application of topical corticosteroids is believed to prevent LVR.
      Patients treated for LS-associated VSCC at a gynaecological cancer centre were
      invited to complete a questionnaire to evaluate whether they are receiving
      corticosteroids. 55 of the 95 eligible patients (58%) completed the
      questionnaire; LS was treated in 69%, with steroids given to 84.2%. Most received
      steroids >3 months, but discontinued treatment once asymptomatic. An online
      survey was distributed to 313 British Gynaecological Cancer Society members to
      determine whether gynaecological oncologists prescribe corticosteroids for LS
      following VSCC surgery. 41 consultants (13.1%) completed the survey; 70.7%
      prescribe topical corticosteroids (potent/very potent in 79.3%), and 58.6% treat
      >1 year. Our findings demonstrate that patients are more likely to be given
      topical corticosteroids if symptomatic of LS. Furthermore, although treatment
      regimens vary, the majority of respondents advocate the use of very potent
      steroids and would support a tertiary chemopreventative trial. Impact statement
      What is already known on this subject: Local vulval recurrence (LVR) affects
      approximately one in four women who have received surgery for vulval squamous
      cell carcinoma (VSCC). What the results of this study add: Lichen sclerosus (LS),
      an inflammatory dermatosis, is recognised as the likely primary aetiological
      factor for LVR. Although there is evidence to suggest that long-term topical
      corticosteroid use in patients with residual LS may prevent LVR, the extent to
      which women were given topical steroids following surgery remains unclear. Our
      patient questionnaire evaluates if these patients are already receiving topical
      steroids, along with the strength of such steroids and duration of treatment. The
      consultant survey determines whether clinicians currently prescribe topical
      steroids following VSCC surgery, as well as the strength and duration of steroid
      therapy. What the implications are of these findings for clinical practice and/or
      further research: We aim to establish whether the gynaecological oncology
      community believe that long-term steroids may prevent LVR in women with LS
      associated VSCC and whether they would support and recruit to a multicentre
      tertiary chemopreventative trial. These findings could influence a future
      clinical trial and may alter the ongoing management of these women.

PMID- 29017364
TI  - Can patients safely be admitted to a ward after craniotomy for resection of intra
      axial brain tumors?
AB  - OBJECTIVE: We reviewed the safety of our practice of admitting patients who have
      undergone a craniotomy for resection of an intra-axial brain tumor to a floor bed
      instead of an ICU. We also tried to quantify the risk that patients electively
      admitted to the ICU would develop a problem that could not have been effectively
      managed on the ward. METHODS: A retrospective chart review was performed of both
      adult and pediatric patients who underwent craniotomy by the senior author for
      resection of an intra-axial brain tumor between January 2012 and December 2015.
      413 patient charts were reviewed; 16 patients were omitted due to incomplete
      records. RESULTS: Four hundred twenty-one craniotomies (393 supratentorial, 28
      infratentorial) were performed in 397 patients, 35 of whom were <18 years of age.
      Three hundred fifty-five patients (83%) were admitted to floor beds; 4 (1.1%)
      developed complications that required transfer to an ICU. None of the 4 died or
      had lasting disability. Sixty-six patients, 51 adults and 15 children, were
      admitted to the ICU after their operation. Twenty-five of these patients had an
      absolute indication for ICU admission: 9 required a ventilator, 14 had an EVD and
      2 were medically unstable. Of the remaining 41, none developed a complication
      that would have required transfer to an ICU had they been on the ward.
      CONCLUSION: It is safe to admit almost all patients to a floor bed after
      craniotomy for intra-axial brain tumor resection. The risk of a catastrophic
      problem occurring after a 4 hour stay in the post anesthesia care unit is
      extremely low. Furthermore, even patients who are electively managed in an ICU
      are unlikely to develop problems that would lead to a worse outcome had they been
      in a floor bed.

PMID- 29017365
TI  - Is the presence of corpus callosum predictable in the first trimester?
AB  - Corpus callosum agenesis (CCA) is a clinical condition accompanied by various
      aneuploidy and genetic syndromes. We identified the development of the corpus
      callosum (CC) in 278 patients before 18 weeks of gestational age by visualising
      the pericallosal artery (PCA) in the callosal sulcus and changes in the lengths
      and ratios of the midbrain (MB) and falx (F), which suggested elevation of the
      third ventricle and thalamus due to CCA in the first trimester. We succeeded in
      visualising the path of the PCA in 273 patients. As expected, we observed an
      increase in the lengths of the MB and F throughout the pregnancies. The MB:F
      ratio was 0.5-0.6, and it was independent of gestational age. In all 278
      patients, the MB:F ratio was <0.6 (95th percentile = 0.79). We observed the
      presence of the CC during anatomical screening at gestational weeks 18-24.
      Visualisation of the PCA path (98% sensitivity) and calculation of the MB:F ratio
      <95th percentile (0.79-100% sensitivity) had very high sensitivity that
      indirectly confirmed the presence of the CC in the first trimester of pregnancy.
      Impact statement What is already known on this subject: After reading the
      articles for detecting the absence of corpus callosum (CC) at first trimester
      with midbrain (MB) and falx (F) measurement by Lachmann et al. ( 2013 ) and
      visualising pericallosal artery (PCA) as an indirect sign of CC agenesis by Pati
      et al. ( 2012 ), we aimed to have a look for our records visualising PCA in
      callosal sulcus and measure MB-F, as well as their ratios for an indirect sign of
      'presence' of CC at first trimester. What the results of this study add: In
      recent literature, it is not possible to find many articles suggesting the
      presence of CC between 11 and 13 weeks of gestation. Diaz-Guerrero et al. ( 2013
      ) and Pati et al. ( 2012 ) has researched visualising PCA path. Lachmann et al. (
      2013 ) reported an article for MB and F measurements in early suspicion of CC
      agenesis. Our study will be the first article in visualising PCA path and
      measuring MB-F lengths as well as their ratios for 'presence' of CC with high
      sensitivity rates (98% and 100%). What are the implications of these findings for
      clinical practice and/or further research: This study encourages clinicians
      visualising PCA path and measure MB-F lengths when they will try to visualise
      repetitive times and see how it is an easy procedure when you get used to it.

PMID- 29017366
TI  - Income Disparities in the Association of the Medical Home With Child Health.
AB  - This study was a secondary data analysis of the 2011-2012 National Survey of
      Children's Health. Data were available for a nationally representative sample of
      81 090 children. Multivariable logistic regression was used to model child health
      with the medical home while examining the effect modification of household income
      and controlling for sociodemographic characteristics. Overall, the medical home
      was significantly associated with "excellent/very good" child health for children
      regardless of household income. However, the association of the medical home with
      "excellent/very good" child health was significantly higher for children in
      households earning >200% FPL (federal poverty level) compared with <200% FPL
      (adjusted odds ratio [aOR] 2.13 [95% CI 1.80-2.52] vs aOR 1.46 [95% CI 1.24
      1.71]; P < .01). This relationship was also found among children >400% FPL
      compared with children between 100% and 199% FPL (aOR 2.25 [95% CI 1.74-2.9 0] vs
      aOR 1.28 [95% CI 1.01-1.62]; P < .01). Therefore, while the medical home is
      associated with beneficial child health for most children, significant
      disparities by income exist.

PMID- 29017368
TI  - The burden of severe hypoglycemia in type 2 diabetes.
AB  - AIMS: More than 29 million people in the US have type 2 diabetes mellitus (T2DM),
      a chronic metabolic disorder characterized by a progressive deterioration of
      glucose control, which eventually requires insulin. Abnormally low levels of
      blood glucose, a feared side-effect of insulin treatment, may cause severe
      hypoglycemia (SHO), leading to emergency department (ED) admission,
      hospitalization, and long-term complications; these, in turn, drive up the costs
      of T2DM. This study's objective was to estimate the prevalence and costs of SHO
      related hospitalizations and their additional longer-term impacts on patients
      with T2DM using insulin. METHODS: Using Truven MarketScan claims, we identified
      adult T2DM patients using basal and basal-bolus insulin regimens who were
      hospitalized for SHO (inpatient SHO patients) during 2010-2015. Two comparison
      groups were defined: those with outpatient SHO-related encounters only, including
      ED visits without hospitalization (outpatient SHO patients), and those with no
      SHO- or acute hyperglycemia-related events (comparison patients). Lengths of stay
      and SHO-related hospitalization costs were estimated, and propensity score and
      inverse probability weighting methods were used to adjust for baseline
      differences across the groups to evaluate longer-term impacts. RESULTS: We
      identified 66,179 patients using basal and 81,876 patients using basal-bolus
      insulin, of which ~1.1% (basal) to 3.2% (basal-bolus) experienced at least one
      SHO-related hospitalization. Among those who experienced SHO (i.e. those in the
      inpatient and outpatient SHO groups), 27% (basal) and 40% (basal-bolus)
      experienced at least one SHO-related hospitalization. One-third of basal and
      about one-quarter of basal-bolus patients were admitted directly to the hospital;
      the remainder were first assessed or treated in the ED. Inpatient SHO patients
      using basal insulin stayed in the hospital, including time in the ED, for 2.8
      days and incurred $6896 in costs; patients using basal-bolus insulin stayed in
      the hospital for 2.6 days and incurred costs of $5802. Forty-to-fifty percent of
      inpatient SHO patients were hospitalized again for SHO. Inpatient SHO patients
      using basal insulin incurred significantly higher monthly costs after their
      initial SHO-related hospitalization than patients in the other two groups ($2935
      vs $1819 and $1638), corresponding to 61% and 79% higher monthly costs; patients
      using basal-bolus insulin also incurred significantly higher monthly costs than
      patients in the other groups ($3606 vs $2731 and $2607), corresponding to 32% and
      38% higher monthly costs. LIMITATIONS: These analyses excluded patients who did
      not seek ED or hospital care when faced with SHO; events may have been miscoded;
      and we were not able to account for clinical characteristics associated with SHO,
      such as insulin dose and duration of diabetes, or unmeasured confounders.
      CONCLUSIONS: The burden associated with SHO is not negligible. Nearly one in
      three patients using only basal insulin and one in four patients using basal
      bolus regimens who experienced SHO were hospitalized at least once due to SHO.
      Not only did those patients incur the costs of their SHO hospitalization, but
      they also incurred at least $1,116 (62%) and $875 (70%) more per month than
      outpatient SHO or comparison patients. Reducing SHO events can help decrease the
      burden associated with SHO among patients with T2DM.

PMID- 29017369
TI  - The Success Rate of Neurology Residents in EEG Interpretation After Formal
      Training.
AB  - EEG is an important tool for neurologists in both diagnosis and classification of
      seizures. It is not uncommon in clinical practice to see patients who were
      erroneously diagnosed as epileptic. Most of the time incorrect interpretation of
      EEG contributes significantly to this problem. In this study, we aimed to
      investigate the success rate of neurology residents in EEG interpretation after
      formal training. Eleven neurology residents were included in the study. Duration
      of EEG training (3 vs 4 months) and time since completion of EEG education were
      determined. Residents were randomly presented 30 different slides of
      representative EEG screenshots. They received 1 point for each correct response.
      The effect of training duration and time since training were investigated
      statistically. Besides, we looked at the success rate of each question to see
      whether certain patterns were more readily recognized than others. EEG training
      duration ( P = .93) and time since completion of training ( P = .16) did not
      influence the results. The success rate of residents for correct responses was
      between 17% and 50%. On the other hand, the success rate for each question varied
      between 0% and 91%. Overall, benign variants and focal ictal onset patterns were
      the most difficult to recognize. On 13 occasions (6.5%) nonepileptiform patterns
      were thought to represent epileptiform abnormalities. After formal training,
      neurology residents could identify <=50% of the EEG patterns correctly. The wide
      variation in success rate among residents and also between questions implies that
      both personal characteristics and inherent EEG features influence successful EEG
      interpretation.

PMID- 29017370
TI  - Valorization of raw materials from agricultural industry for astaxanthin and beta
      carotene production by Xanthophyllomyces dendrorhous.
AB  - Waste deriving from food and agro-industries is a growing problem in our modern
      society. In order to reduce food waste and its associated impacts over the
      environment and public health, innovative strategies for the conversion of food
      wastes in added value products are studied. Whey is one of the prominent waste
      deriving from Sicilian diary industry. The growth and the carotenoid biosynthesis
      of the yeast Xanthophyllomyces dendrorhous by its cultivation in pre-treated whey
      were studied. The study showed the possibility of increasing the astaxanthin
      productivity from X. dendrorhous in a batch fermentative process under continuous
      illumination. Our work is focused on the importance of carotenogenesis by X.
      dendrorhous on whey for the economic and ecological aspect. The results obtained
      in the study provide useful information about the possible use of this waste
      material for carotenogenesis from X. dendrorhous.

PMID- 29017371
TI  - Cytarabine and daunorubicin for the treatment of acute myeloid leukemia.
AB  - INTRODUCTION: Acute myeloid leukemia (AML) is the most common acute forms of
      leukemia in adults. It has a poor long-term survival with a high relapse rate and
      at relapse, is commonly resistant to available therapies. The current combination
      of daunorubicin (DNR) for three days and cytarabine (Ara-C) as a continuous
      infusion for seven days, more commonly known as '3 + 7' has remained essentially
      unaltered over the last forty-four years and remains the standard induction
      regimen internationally. Areas covered: This paper will briefly review clinically
      important trials related to '3 + 7'. Somatic mutations in AML that are linked to
      chemoresistance to '3 + 7'will be discussed. Other topics covered include the
      novel ratiometric agent containing daunorubicin and cytarabine, CPX-351, and
      midostaurin in FLT3 mutated AML. Expert opinion: '3 + 7' continues to be the
      backbone of therapy for AML. However, genetic risk stratification should be used
      to determine patients who are unlikely to respond to standard intensive
      chemotherapy and hence, should be enrolled onto a clinical trial upfront. This
      will facilitate development of newer effective treatment strategies in AML.
      Patients with mutations that are associated with chemoresistance should be
      offered therapies which may circumvent or overcome these pathways.

PMID- 29017372
TI  - The antidepressant-like activity of ellagic acid and its effect on hippocampal
      brain derived neurotrophic factor levels in mouse depression models.
AB  - The aim of present study was to evaluate the antidepressant-like activity of
      ellagic acid (EA) in mice-forced swim test (FST) and tail suspension test (TST)
      and the possible role of brain-derived neurotrophic factor (BDNF) in EA's
      antidepressant-like effect. We found that EA and sertraline did not affect the
      spontaneous locomotor activity of mice. EA produced statistically significant
      decrease in immobility time as compared to vehicle group in TST. EA at 1 and 5
      mg/kg doses did not produce any significant effect in immobility time as compared
      to vehicle group in FST. But EA produced significantly reduced immobility time at
      2.5 mg/kg dose. EA treatment increased hippocampal BDNF level. This study
      demonstrates that EA is able to produce antidepressant-like effect in both TST
      and FST in mice. Moreover, the antidepressant-like effects of EA seems to be
      mediated by increased BDNF level in mice hippocampus.

PMID- 29017373
TI  - Clinical considerations for use of insulin degludec/insulin aspart in Japanese
      patients.
AB  - INTRODUCTION: Co-formulation of basal and bolus insulin components provides a
      simpler regimen for patients with type 2 diabetes than separate basal-bolus
      treatment. However, conventional premixed insulin products include a suboptimal
      protaminated basal component that requires resuspension prior to injection.
      Insulin degludec/insulin aspart (IDegAsp) is the first soluble co-formulation of
      a basal insulin with an ultra-long duration of action (IDeg) and a rapid-acting
      bolus insulin (IAsp) in a single injection. Areas covered: In this review, the
      authors summarize findings from pre-clinical studies and the clinical trial
      program and provide guidance for the initiating and switching of IDegAsp in
      different patient populations. Pharmacodynamic analyses have revealed a rapid
      onset of action and distinct peak (IAsp), followed by a separate, flat and stable
      basal effect (IDeg component). Phase 3 studies have demonstrated the efficacy and
      safety of IDegAsp, with greater glycemic improvements than basal-only therapy in
      international and Japanese type 2 diabetes populations. IDegAsp also results in
      reduced insulin dose requirements and lower rates of hypoglycemia than premixed
      insulin. Expert opinion: IDegAsp provides a simple and effective insulin regimen
      in appropriately selected Japanese patients, with the flexibility to suit
      individual needs. The benefits of IDegAsp over conventional insulin regimens
      might help tackle clinical inertia with insulin intensification.

PMID- 29017374
TI  - Prevalence of Sexually Transmitted Infections and Their Risk Factors among Female
      Sex Workers in Isfahan, Iran: A Cross-Sectional Study.
AB  - OBJECTIVES: Female sex workers (FSWs) are at high risk of sexually transmitted
      infections (STIs) and form a core group to facilitate STI spreading. We aimed to
      estimate the prevalence of STIs among FSWs who attended Female Harm Reduction
      Center of Isfahan, Iran, and to determine the association between risky behaviors
      and STIs. STUDY DESIGN: In a cross-sectional study, 99 FSWs were recruited and
      interviewed about demographic characteristics and risky behaviors. A trained
      midwife examined FSWs for genital ulcer, abnormal vaginal discharge, and
      cervicitis. Urine and genital specimens were collected and real-time polymerase
      chain reaction was performed to diagnose Neisseria gonorrhoeae, human papilloma
      virus (HPV), and Trichomonas Vaginalis. Data were analyzed via chi2 test and
      logistic regression in StataCorp software (version 11) with 95% confidence
      interval. RESULTS: Totally, 84.9% of FSWs reported STI symptoms, while 12.1% of
      them were infected with N gonorrhoeae, HPV, or T vaginalis. Human papilloma virus
      and gonorrhea prevalence rates were 5.7% and 8% in FSWs with STI-associated
      symptoms. Sexually transmitted infections showed significant association with
      duration of prostitution (odds ratio [OR]HPV = 1.009 [95% confidence interval
      [95% CI: 1.004-1.01]; ORgonorrhea = 1.01 [95% CI: 1.00-1.01]) and condom usage
      (ORHPV = 0.11 [95% CI: 0.012-0.98]; ORgonorrhea = 0.04 [95% CI: 0.005-0.33]).
      CONCLUSION: Due to the literature gap on the Iranian FSWs' sexual health and the
      intense stigma around this subject, in Iran, our results would be useful for
      developing an efficient intervention program. The prevalence of STIs in Isfahan
      FSWs can be controlled with programs such as consistent condom use and STI
      treatment. In addition, as just one-tenth of FSWs with an STI symptom were
      positive for an STI, symptomatic diagnosis of STIs might be insufficient.

PMID- 29017375
TI  - HIV Nurse Navigation: Charting the Course to Improve Engagement in Care and HIV
      Virologic Suppression.
AB  - This study represents one of the few exploring the effectiveness of an integrated
      HIV nurse navigation program on engagement and virologic outcomes. A navigator
      provided individualized care management (eg, pillbox renewals), intensive
      outreach, and collaboration with existing support systems (eg, families,
      community programs). Clinical data from the Veterans Affairs (VA) Medical Center
      site of a longitudinal, observational study of HIV in the District of Columbia
      (DC) cohort were used for comparison (N = 706). Navigation patients (n = 84) were
      less likely to have permanent housing, and more likely to be disabled, have
      detectable viral load, comorbid depressive, and substance use disorders.
      Navigation patients showed improvements in clinic visits (doubled), rate of
      medication renewal (40.91% to 80.61%), CD4 count and CD4%, and viral rates of
      Veterans with <200 copies/mL increased from 47.6% to 69.0% after one year.
      Integration of nurse navigation into a HIV primary care setting shows promise in
      improving engagement and virologic suppression in a high-risk population.

PMID- 29017376
TI  - Bilateral Multiple Mammary Myofibroblastomas in an Adult Male.

PMID- 29017377
TI  - Early maladaptive schemas in patients with bipolar and unipolar disorder.
AB  - OBJECTIVE: The aim of our study is to determine the difference between the
      bipolar disorder, unipolar disorder and control groups in terms of maladaptive
      schemes and childhood trauma. METHODS: Two groups of patients under monitoring
      with a diagnosis of bipolar or unipolar disorder and one group of healthy
      controls were enrolled in this study. Each group consisted of 60 subjects. The
      Young Mania Rating Scale and Beck Depression Inventory were used to confirm that
      patients were in remission. The Childhood Trauma Questionnaire and Young Schema
      Questionnaire-Short Form 3 were used to identify childhood traumas and early
      maladaptive schemas. RESULTS: In bipolar disorder, a positive, low power
      correlation was observed between the vulnerability to threats schema and
      emotional, physical and sexual abuse. In the unipolar disorder group, there was a
      positive, low power correlation between the emotional inhibition, failure,
      approval seeking, dependence, abandonment and defectiveness schemas and social
      isolation, and a positive, moderate correlation between social isolation and
      emotional abuse. CONCLUSIONS: Individuals with bipolar disorder suffered greater
      childhood trauma compared to subjects with unipolar disorder and healthy
      individuals. Greater maladaptive schema activation were present in individuals
      with bipolar disorder compared to those with unipolar disorder and healthy
      individuals.

PMID- 29017378
TI  - Optimizing Human Induced Pluripotent Stem Cell Expansion in Stirred-Suspension
      Culture.
AB  - Human induced pluripotent stem cells (hiPSCs) hold great hopes for application in
      regenerative medicine due to their inherent capacity to self-renew and
      differentiate into cells from the three embryonic germ layers. For clinical
      applications, a large quantity of hiPSCs produced in standardized and scalable
      culture processes is required. Several groups, including ours, have developed
      methodologies for scaled-up hiPSC production in stirred bioreactors in chemically
      defined medium. In this study, we optimized the critical steps and factors that
      affect hiPSC expansion and yield in stirred-suspension cultures, including
      inoculation conditions, seeding density, aggregate size, agitation rate, and cell
      passaging method. After multiple passages in stirred-suspension bioreactors,
      hiPSCs remained pluripotent, karyotypically normal, and capable of
      differentiating into all three germ layers.

PMID- 29017379
TI  - HLA-associated drug hypersensitivity and the prediction of adverse drug
      reactions.
AB  - Adverse drug reactions are an important cause of morbidity and mortality and
      constitute the leading reason of drug withdrawal from the market. Besides
      classical reactions that are related to pharmacologic activity of the drug, some
      reactions are unpredictable, not dose dependent, and seem to occur in genetically
      predisposed individuals. The majority of this reaction is immunologically driven
      and they are referred to as hypersensitivity reactions. A growing number of
      studies provided evidences that specific HLA alleles increase the risk of
      developing hypersensitivity drug reactions. In this context, drug
      hypersensitivities that have more robust pharmacogenetic data include abacavir
      hypersensitivity syndrome and severe cutaneous adverse reactions induced by
      allopurinol and carbamazepine.

PMID- 29017380
TI  - A "Collective Effort to Make Yourself Feel Better": The Group Process in
      Mindfulness-Based Interventions.
AB  - There is growing interest in mindfulness-based interventions (MBIs) in the
      management of multiple physical and mental health issues. Although MBIs utilize a
      group format, research on how this format impacts teaching and learning
      mindfulness is lacking. This study aimed to develop a detailed theory of MBI
      group processes utilizing a grounded theory methodology. This article presents
      our subsequent model, developed from semistructured interviews conducted with MBI
      students, teachers, and trainers ( N = 12). A core category, the group as a
      vessel on a shared journey, and three higher-order categories emerged from the
      data. They illustrate how MBI group processes navigate a characteristic path.
      Teachers build and steer the group "vessel" in a way that fosters a specific
      culture and sense of safety. The group is facilitated to share communal
      experiences that augment learning and enrich mindfulness practice. Limitations
      and implications for clinicians and researchers are discussed.

PMID- 29017381
TI  - Special focus issue on regenerative medicine in society: interdisciplinary
      perspectives (part I) - Foreword.

PMID- 29017382
TI  - Which factors are associated with the recurrence of endometrioma after
      cystectomy?
AB  - Endometrioma is the most common form of endometriosis and is a sign of wide
      spread disease in symptomatic patients. Medical treatment options can be
      successful in endometrioma smaller than 1 cm, but ineffective for growing and
      symptomatic endometriomas. Conservative surgical interventions that preserve
      fertility, such as laparoscopic removal or destruction of endometriotic tissue or
      aspiration of cystic content are typically used to treat the condition. One of
      the most frustrating aspects of endometrioma treatment is disease recurrence. The
      underlying mechanisms explaining recurrence are uncertain. Several risk factors
      have been evaluated in order to predict recurrence after cystectomy. In looking
      at the results overall, our study can conclude that the presence of greater cyst
      dimension, higher CA-125 level, presence of preoperative symptoms of non-cyclic
      pelvic pain, dysmenorrhoea and adhesion extension may be associated with
      recurrent endometrioma. In clinical practice, identification of risk factors for
      recurrence helps clinicians to inform patients. Impact statement What is already
      known on this subject: Endometrioma is the most common form of endometriosis and
      is a sign of wide-spread disease in symptomatic patients. One of the most
      frustrating aspects of endometrioma treatment is disease recurrence. Several risk
      factors have been evaluated in order to predict recurrence after cystectomy.
      However, the risk factors have not been precisely defined. What the results of
      this study add: This study aimed to investigate the contribution of possible risk
      factors to the recurrence of endometrioma after laparoscopic surgery. In looking
      at the results overall, our study can conclude that the presence of greater cyst
      dimension, higher CA-125 level, adhesion extension, presence of preoperative
      symptoms of non-cyclic pelvic pain and dysmenorrhoea may be associated with
      recurrent endometrioma. What the implications of these findings are for clinical
      practice and/or further research: In clinical practice, identification of risk
      factors for recurrence helps clinicians to inform patients. Detection of
      preoperative risk factors would be helpful in counselling patients on their
      future prognosis. This may also increase treatment success by providing accurate
      preoperative treatment planning and by assisting the scheduling of postoperative
      follow-ups.

PMID- 29017383
TI  - Acetabular labrum of hip joint in osteoarthritis: A qualitative original study
      and short review of the literature.
AB  - PURPOSE: Histological architecture of normal acetabular labrum regarding free
      nerve endings (FNEs) and mechanoreceptors (MRs) has been satisfactorily described
      in the literature. However, the presence of FNEs and MRs in acetabular labrum of
      hip joint has been analyzed only once in patients with osteoarthritis (OA). Aim
      of this article is to report histological distribution pattern of FNEs and MRs in
      acetabular labrum of patients with severe OA, at the same time conducting a
      comparison with normal acetabular labrum described in the literature. METHODS:
      Seven patients with severe hip OA were enrolled in this study. Patient selection
      was assisted by the utilization of specific clinical scales delineated by the
      American College of Rheumatology. After successful total hip arthroplasty, tissue
      samples of acetabular labra of seven patients were histologically processed and
      stained with the gold standard chloride method, which was subsequently examined
      under a compound microscope. RESULTS: FNEs and MRs constituted the major
      histological structures. Identified MRs included Pacini corpuscles, Ruffini
      corpuscles, and Golgi-Mazzoni corpuscles. The presence of FNEs was predominant in
      the middle part of the acetabular labrum, featuring a remarkable decrease in
      peripheral parts. In contrast, MRs were detected basically in peripheral parts
      and less in the middle part. CONCLUSIONS: Differentiation of the distribution
      pattern of MRs and FNEs in acetabular labrum of hip joint is remarkable between
      normal patients and patients with severe OA. The abundance of FNEs in the middle
      part of the pathologic labrum is mainly responsible for the observed
      discrimination. A "conversion" of MRs to FNEs may occur during OA progression,
      modulating therefore this pattern as well as the upcoming clinical
      manifestations.

PMID- 29017384
TI  - Leukocyte Cell-Derived Chemotaxin-2 Amyloidosis (ALECT2) in a Patient With Lung
      Adenocarcinoma: An Autopsy Report and Literature Review.
AB  - Amyloidosis caused by deposition of leukocyte cell-derived chemotaxin-2
      amyloidosis (ALECT2) is the most recently described form of systemic amyloidosis
      and has quickly emerged as a common and possibly underdiagnosed cause of slowly
      declining renal function, particularly in patients of Hispanic ancestry. We
      describe the autopsy findings in a 70-year-old Hispanic woman who died of
      metastatic lung adenocarcinoma and was incidentally found to have extensive
      amyloid deposition in the kidneys, liver, spleen, adrenal glands, small
      intestine, gallbladder, lungs, bilateral ovaries, and uterus. The type of amyloid
      was confirmed to be ALECT2 by mass spectrometry. The pattern of amyloid
      deposition in the kidneys and the liver was typical for what has been described
      for ALECT2. In addition, a unique pattern of amyloid deposition was observed in
      spleen, adrenal glands, small intestine, gallbladder, lungs, ovaries, and uterus.
      The pattern of amyloid deposition in ALECT2 is distinct from amyloid A and
      amyloid light-chain and needs to be recognized to avoid misdiagnosis as amyloid
      light-chain or amyloid A amyloidosis. After recognition, an accurate diagnosis by
      mass spectrometry and/or immunohistochemical staining is essential to guide
      treatment and avoid toxic therapies.

PMID- 29017385
TI  - Patient satisfaction in the long-term effects of Eustachian tube balloon dilation
      is encouraging.
AB  - OBJECT: To investigate the long-term effects of balloon Eustachian tuboplasty
      (BET) from patient's perspective and to discover which symptoms of Eustachian
      tube dysfunction (ETD) benefit the most from BET. METHOD: We designed a
      retrospective postal questionnaire based on the seven-item ETD questionnaire
      (ETDQ-7). Our questionnaire covered the severity of present ETD symptoms in
      comparison with the preoperative situation, the severity of current overall ear
      symptoms, and possible surgical interventions after BET. Forty-six patients
      treated in our institution between 2011 and 2013 fulfilled the inclusion criteria
      and 74% (34 patients; total 52 ears treated with BET) returned the questionnaire
      with a mean follow-up time of 3.1 years (range 1.8-4.6 years). RESULTS: Pain in
      the ears, feeling of pressure in the ears, and feeling that ears are clogged had
      reduced in 75% of the ears that suffered from these symptoms preoperatively.
      Seventy-seven percent of all the responders felt that their overall ear symptoms
      were reduced. Altogether, 82% of all the patients stated that they would undergo
      BET again if their ear symptoms returned to the preoperative level. CONCLUSION:
      Patient satisfaction in the long-term effects of BET is encouraging. These
      results may help clinicians in preoperative patient selection and counselling.

PMID- 29017386
TI  - A peri-urethral mass - what are the possible diagnoses?

PMID- 29017387
TI  - Concentration-dependent protein adsorption at the nano-bio interfaces of
      polymeric nanoparticles and serum proteins.
AB  - AIM: A comprehensive understanding of nanoparticle (NP)-protein interaction
      (protein corona formation) is required. So far, many factors influencing this
      interaction have been investigated, like size and zeta potential. However, NPs
      exposure concentration has always been ignored. Herein, we aim to disclose the
      correlation of NPs exposure concentration with protein adsorption. MATERIALS &
      METHODS: Four polymeric NPs systems possessing similar sizes (230 +/- 20 nm) but
      varied zeta potentials (-30 ~ +40 mv) were prepared. Physicochemical properties
      and protein adsorption upon NP-protein interaction were characterized. RESULTS:
      Protein adsorption capacity and adsorbed protein types were NPs concentration
      dependent. CONCLUSION: Considering the critical impacts of protein adsorption on
      NPs delivery, our work could be an urgent warning about the possible risks of
      dosage adjustment of nanoformulations.

PMID- 29017388
TI  - Pathophysiological Bases of Comorbidity: Traumatic Brain Injury and Post
      Traumatic Stress Disorder.
AB  - The high rates of traumatic brain injury (TBI) and post-traumatic stress disorder
      (PTSD) diagnoses encountered in recent years by the United States Veterans
      Affairs Healthcare System have increased public awareness and research
      investigation into these conditions. In this review, we analyze the neural
      mechanisms underlying the TBI/PTSD comorbidity. TBI and PTSD present with common
      neuropsychiatric symptoms including anxiety, irritability, insomnia, personality
      changes, and memory problems, and this overlap complicates diagnostic
      differentiation. Interestingly, both TBI and PTSD can be produced by overlapping
      pathophysiological changes that disrupt neural connections termed the
      "connectome." The neural disruptions shared by PTSD and TBI and the comorbid
      condition include asymmetrical white matter tract abnormalities and gray matter
      changes in the basolateral amygdala, hippocampus, and prefrontal cortex. These
      neural circuitry dysfunctions result in behavioral changes that include executive
      function and memory impairments, fear retention, fear extinction deficiencies,
      and other disturbances. Pathophysiological etiologies can be identified using
      experimental models of TBI, such as fluid percussion or blast injuries, and for
      PTSD, using models of fear conditioning, retention, and extinction. In both TBI
      and PTSD, there are discernible signs of neuroinflammation, excitotoxicity, and
      oxidative damage. These disturbances produce neuronal death and degeneration,
      axonal injury, and dendritic spine dysregulation and changes in neuronal
      morphology. In laboratory studies, various forms of pharmacological or
      psychological treatments are capable of reversing these detrimental processes and
      promoting axonal repair, dendritic remodeling, and neurocircuitry reorganization,
      resulting in behavioral and cognitive functional enhancements. Based on these
      mechanisms, novel neurorestorative therapeutics using anti-inflammatory,
      antioxidant, and anticonvulsant agents may promote better outcomes for comorbid
      TBI and PTSD.

PMID- 29017389
TI  - The Canadian laboratory initiative on pediatric reference intervals: A CALIPER
      white paper.
AB  - Laboratory investigations provide physicians with objective data to aid in
      disease diagnosis, clinical decision making, and patient follow up. Clinical
      interpretation of laboratory test results relies heavily on the availability of
      appropriate population-based reference intervals (i.e. normative values) or
      decision limits developed through clinical outcome studies. Although reference
      intervals are fundamental to accurate laboratory test interpretation, and thus
      critically important to healthcare, the need for sound evidence-based reference
      intervals has been largely overlooked, particularly in the pediatric population.
      In the field of pediatric laboratory medicine, accurate age- and sex-specific
      reference intervals established using samples from healthy children and
      adolescents have not been readily available, forcing many clinical laboratories
      to report adult reference intervals with pediatric test results. When pediatric
      reference intervals are available, they have often been established with a small
      sample size, inpatient or outpatient samples, outdated methodologies, and/or
      inappropriate statistical procedures. To address these unacceptable limitations,
      several national and global initiatives have begun to close the critical evidence
      gaps in pediatric reference intervals. Notably, the Canadian Laboratory
      Initiative on Pediatric Reference Intervals (CALIPER) has made significant
      strides towards improving pediatric healthcare in Canada and globally. The
      present report is a white paper summarizing CALIPER, and provides a comprehensive
      compendium of the data generated through this project over the past decade as a
      single resource for clinical laboratory specialists, clinicians, and other
      healthcare workers. CALIPER launched an outreach campaign in 2008 to recruit
      healthy community children and adolescents, and developed a robust statistical
      algorithm, in accordance with the Clinical and Laboratory Standards Institute
      (CLSI) guidelines, to develop accurate age- and sex-specific pediatric reference
      intervals. The first CALIPER direct reference interval study was published in
      2012, with age- and sex-specific reference intervals reported for 40 common
      biochemical markers. To date, CALIPER has collected health information and blood
      samples from over 9700 community children and adolescents, and has established a
      comprehensive database of age- and sex-specific reference intervals for over 100
      biomarkers of pediatric disease. CALIPER has also performed a series of
      transference and verification studies to expand the applicability of the CALIPER
      database to five major analytical platforms, including Abbott, Beckman, Ortho,
      Roche, and Siemens. Through novel knowledge translation initiatives, the CALIPER
      Reference Interval Database has been made freely available online (
      www.caliperproject.ca ) as well as on a mobile application (CALIPER Reference
      App), and it is used by clinical laboratories across Canada, the United States,
      and globally. In addition to establishing this comprehensive pediatric reference
      interval database, CALIPER has also performed a series of sub-studies, including
      examining how reference intervals are affected by pre-analytical factors (i.e.
      sample stability at specific storage conditions, fasting status and time of
      sample collection), biological variation (i.e. intraindividual and
      interindividual biological variation, reference change values), and ethnicity and
      pubertal development stage. In this white paper, extensive tables of pediatric
      reference intervals are provided for easy reference for clinical laboratories
      worldwide. All data reported have been published in over 20 peer reviewed
      publications and are also available through the CALIPER Reference Interval
      Database as well as the CALIPER Reference App for mobile devices.

PMID- 29017390
TI  - Pharmacokinetics of praziquantel and pyrantel pamoate combination following oral
      administration in cats.
AB  - Objectives The pharmacokinetics of praziquantel and pyrantel pamoate has never
      been reported in cats. The present study was designed to establish the plasma
      concentration-time profile and to derive pharmacokinetic data for a combined
      formulation of praziquantel and pyrantel in cats, after a single, oral
      administration. Methods Twenty-two clinically healthy adult cats were used, each
      receiving a single oral dose of praziquantel (8.5 mg/kg) and pyrantel (100
      mg/kg). Blood samples were collected at regular time points up to 48 h post
      dosing. Plasma concentrations of praziquantel and pyrantel were measured using a
      liquid chromatography-mass spectrometry-high-throughput screening method. Results
      Clinical examination of all cats did not reveal any side effects after oral
      administration of these medications. The terminal half-life for praziquantel and
      pyrantel was 1.07 and 1.36 h, respectively. Praziquantel peak concentration
      (Cmax) was 1140 MUg/ml, reached at 1.22 h. The plasma concentrations of pyrantel
      after oral administration were low with a mean Cmax of 0.11 MUg/ml, reached at a
      Tmax of 1.91 h. Pyrantel showed a very limited absorption as pamoate salt,
      suggesting permanence and efficacy inside the gastrointestinal tract, where the
      adult stages of most parasitic nematodes reside. Conclusions and relevance
      Pyrantel showed a very limited absorption as pamoate salt. Praziquantel was
      rapidly absorbed following oral administration and the concentrations achieved
      suggest that praziquantel could be an effective and safe medication in cats.
      Although some resistance problems are arising as a result of their long use,
      these anthelminthic products can still play a major role in parasitic control,
      especially in geographical areas where the high cost of newer treatments or
      necessity of parenteral administration could decrease the number of treated
      animals.

PMID- 29017391
TI  - Friends With Performance Benefits: A Meta-Analysis on the Relationship Between
      Friendship and Group Performance.
AB  - The current article examines if, and under which conditions, there exists a
      positive relationship between working with friends and group performance. To do
      so, using data from 1,016 groups obtained from 26 studies, we meta-analyzed
      comparisons of the performance of friendship groups versus acquaintance groups.
      Results show that friendship has a significant positive effect on group task
      performance (Cohen's d = 0.31). Furthermore, this relationship was moderated by
      group size (i.e., the positive effect of friendship on performance increased with
      group size) and task focus (i.e., friendship groups performed better than
      acquaintance groups on tasks requiring a high quantity of output, whereas there
      was no performance benefit on tasks requiring a single or high-quality output).
      These results help to reconcile mixed findings and illustrate when friendship
      groups are more likely to perform better than acquaintance groups.

PMID- 29017392
TI  - A new chromosomal arrangement due to paternal balanced translocation for
      syndromic oesophageal atresia: case report.

PMID- 29017393
TI  - Expression of hsa-let-7b-5p, hsa-let-7f-5p, and hsa-miR-222-3p and their putative
      targets HMGA2 and CDKN1B in typical and atypical carcinoid tumors of the lung.
AB  - Typical and atypical carcinoid tumors belong to the neuroendocrine lung tumors.
      They have low recurrence and proliferation rate, lymph node, and distant
      metastases. Nevertheless, these tumors have shown a more aggressive behavior. In
      the last years, microRNAs were screened as new tumor markers for their potential
      diagnostic and therapeutic relevance. The expression of hsa-let-7b-5p, hsa-let-7f
      5p, hsa-miR-222-3p, and their targets HMGA2 (high-mobility group A2) and CDKN1B
      (cyclin-dependent kynase inhibitor 1B, p27kip1) was evaluated in this rare small
      group of patients. We analyzed the clinical data of all typical and atypical
      carcinoid tumors of patients who underwent surgical operation at Marburg
      University Hospital (n = 18) from 2000. Quantitative reverse transcription
      polymerase chain reaction was performed in formalin-fixed paraffin-embedded tumor
      tissue versus four tumor-free lung tissue samples. HMGA2 was stable or
      downregulated; only one patient showed a significant overexpression. CDKN1B
      showed a significant overexpression or a stable level; it was downregulated in
      two samples only. Hsa-miR-222-3p resulted almost stable or overexpressed except
      for two samples (significantly downregulated). Hsa-let-7f-5p was stable or
      overexpressed in the majority of analyzed samples, whereas hsa-let-7b-5p was
      significantly downregulated. HMGA2 and CDKN1B are differently expressed between
      atypical and typical carcinoid tumors, thus representing valid biomarkers for the
      classification of the two tumor groups. Hsa-let-7f-5p and HMGA2 are inversely
      correlated. Hsa-miR-222-3p does not correlate with its predicted target CDKN1B.

PMID- 29017394
TI  - A preliminary study of gut dysbiosis in children with food allergy.
AB  - Gut microbiota of food allergic children was analyzed by high throughput 16S rRNA
      gene sequencing. Signs of gut dysbiosis, which is likely associated with gut
      inflammation, was observed in children with food allergies. For example,
      decreased abundance of genus Akkermansia but increased abundance of Veillonella
      was found in children with food allergy in comparison with healthy control
      children.

PMID- 29017395
TI  - Electrical support during outdoor cycling in patients with coronary artery
      disease: impact on exercise intensity, volume and perception of effort.
AB  - BACKGROUND: Electrical assisted bicycles (EAB's) could be used to overcome
      barriers and difficulties to outdoor cycling and thus assist in achieving a
      sufficient physical activity level in coronary artery disease (CAD) patients, but
      it is unknown whether sufficient exercise intensities and volumes could be
      elicited during cycling on EAB's. In this study we examined, for the first time,
      the acute physiological impact of electrical support during outdoor cycling in
      CAD patients (ISRCTN32238279). METHODS: Fifteen CAD patients (13 males), aged 64
      +/- 7 years executed a maximal cardiopulmonary exercise test and afterwards
      cycled a predefined outdoor route of 10 km, in three different conditions:
      classical cycling (no support), EAB with low support (EABlow) and high support
      (EABhigh). Oxygen uptake (VO2) and carbon dioxide output (VCO2) was measured
      continuously by a portable gas-analysing system. Cycling time was recorded and
      ratings of perceived exertion (RPE) was assessed at 3 and 7 km. RESULTS: Mean VO2
      during EABhigh (1721 +/- 537 ml*min-1) was significantly lower compared to EABlow
      (1890 +/- 619 ml*min-1, p < .05), but no differences were found between EABlow
      and classical cycling (1846 +/- 523 ml*min-1). EABlow and EABhigh elicited a
      sufficient volume and intensity (6.6 +/- 2.0 MET's (74 +/- 6% VO2peak) and 6.0 +/
      1.8 MET's (68 +/- 7% VO2peak), respectively) to adhere to the guidelines for
      secondary prevention in CAD. RPE was significantly lower p < .05) during EABhigh
      (9 +/- 2), than during EABlow (11 +/- 2) or classical cycling (11 +/- 2).
      CONCLUSIONS: Outdoor cycling with electrical support leads to a sufficiently high
      exercise intensity and volume in CAD patients, and may be considered as an
      alternative exercise modality.

PMID- 29017396
TI  - Influence of awareness and availability of medical alternatives on parents
      seeking paediatric emergency care.
AB  - AIMS: Direct seeking of care at paediatric emergency departments may result from
      an inadequate awareness or a short supply of medical alternatives. We therefore
      evaluated the care-seeking patterns, availability of medical options and initial
      medical assessments - with overall reference to socioeconomic status - of parents
      at an urban paediatric emergency department in a Scandinavian country providing
      free paediatric healthcare. METHODS: The parents of children assessed by
      paediatric emergency department physicians at a Swedish university hospital over
      a 25-day winter period completed a questionnaire on recent medical contacts and
      their reasons for attendance. Additional information was obtained from ledgers,
      patient records and population demographics. RESULTS: In total, 657 of 713
      eligible patients (92%) were included. Seventy-nine per cent of their parents
      either failed to or managed to establish medical contact before the emergency
      department visit, whereas 21% sought care with no attempt at recent medical
      contact. Visits with a failed telephone or primary care contact (18%) were more
      common outside office hours ( p=0.014) and were scored as less urgent ( p=0.014).
      A perceived emergency was the main reason for no attempt at medical contact
      before the visit. Direct emergency department care-seeking was more common from
      the city district with the lowest socioeconomic status ( p=0.027). CONCLUSIONS:
      Although most parents in this Swedish study tried to seek medical advice before
      attending a paediatric emergency department, perceived emergency, a short supply
      of telephone health line or primary care facilities and lower socioeconomic
      status contributed to direct care-seeking by almost 40% of parents. Pre-hospital
      awareness and the availability of medical alternatives with an emphasis on major
      differences in socioeconomic status should therefore be considered to further
      optimize care-seeking in paediatric emergency departments.

PMID- 29017397
TI  - Liver Scaffolds Support Survival and Metabolic Function of Multilineage Neonatal
      Allogenic Cells.
AB  - Organ scaffold bioengineering is currently limited by the inability to
      effectively repopulate the scaffold with appropriately distributed functional
      cells. We examined the feasibility of a decellularized liver scaffold to support
      the growth and function of multilineage allogenic cells derived from either adult
      or neonatal liver cells. Cell slurries from neonatal and adult rat livers
      containing hepatocytes, cholangiocytes, and endothelial cells were introduced
      into decellularized adult rat liver scaffolds via the bile duct. Recellularized
      grafts were perfused with cell growth medium through the portal vein for 7 days.
      Concurrently, the same cell slurries were incubated on culture dishes. Albumin
      levels were measured from graft perfusates and cell culture media.
      Immunofluorescent assays were used to verify the colocalization of
      cholangiocytes, hepatocytes, endothelial cells, and Kupffer cells in the
      recellularized grafts by using anti-CK7, anti-hepatocyte antigen, anti-CD34, and
      anti-CD68, respectively. More robust albumin production was detected in the
      perfusate of scaffolds recellularized with a neonatal liver cell slurry compared
      with those with an adult liver cell slurry. The perfusates from all
      recellularized grafts showed increasing albumin concentration over 7 days; higher
      levels were detected in the constructs compared with the cell culture. Scaffolds
      seeded with a neonatal liver cell slurry showed the presence of hepatocytes,
      cholangiocytes, endothelial cells, and Kupffer cells. Results demonstrated the
      superiority of neonatal allogenic cells over adult cells of the same origin,
      possibly because of their pluripotent behavior. Liver bio-scaffolds supported the
      growth of four different liver cell lines. Recellularized grafts exhibited
      preserved functionality as demonstrated by albumin production, and constructs
      seeded with a neonatal cell slurry demonstrated proliferation on Ki-67 assay,
      thus representing a promising model for a transplantable construct.

PMID- 29017398
TI  - An enzymatic method for the production of 6-oxohexanoic acid from 6-aminohexanoic
      acid by an enzyme oxidizing omega-amino compounds from Phialemonium sp. AIU 274.
AB  - An enzymatic method for 6-oxohexanoic acid production was developed using 6
      aminohexanoic acid and an omega-amino group-oxidizing enzyme (omega-AOX) from
      Phialemonium sp. AIU 274. 6-Oxohexanoic acid was produced from 6-aminohexanoic
      acid with 100% yield by incubation with 0.3 U of the omega-AOX and 20 U of
      catalase at 30  degrees C for 30 h in 0.1 M potassium phosphate buffer (pH 7.0).

PMID- 29017399
TI  - Recombinant expression, purification, and characterization of polyphenol oxidase
      2 (VvPPO2) from "Shine Muscat" (Vitis labruscana Bailey * Vitis vinifera L.).
AB  - Polyphenol oxidases (PPOs) catalyze browning reactions in various plant organs,
      therefore controlling the reactions is important for the food industry. PPOs have
      been assumed to be involved in skin browning of white grape cultivars; however,
      the molecular mechanism underlying PPO-mediated browning process remains elusive.
      We have recently identified a new PPO gene named VvPPO2 from "Shine Muscat"
      (Vitis labruscana Bailey * V. vinifera L.), and have shown that the gene is
      transcribed at a higher level than the previously identified VvPPO1 in browning,
      physiologically disordered berry skins at the maturation stage. In this study, we
      expressed VvPPO2 in Escherichia coli and, using the purified preparation,
      revealed unique physicochemical characteristics of the enzyme. Our study opens up
      a way to not only understand the berry skin browning process but also to
      elucidate the enzymatic maturation process of grape PPOs.

PMID- 29017400
TI  - Case report: Minimally invasive method to activate the expiratory muscles to
      restore cough.
AB  - CONTEXT: Spinal cord stimulation (SCS) via disc electrodes surgically placed via
      laminotomy incisions has been shown to restore an effective cough in subjects
      with spinal cord injury (SCI). The purpose of this study was to evaluate a new
      method of expiratory muscle activation utilizing spinal cord wire leads, which
      can be implanted with minimally invasive techniques. METHODS: In a subject with
      SCI, parallel wire leads with two electrode contacts were inserted percutaneously
      through a needle, advanced to the T9, T11 spinal levels and connected to an
      implanted radiofrequency receiver. Stimulus parameters were set at values
      resulting in near maximum airway pressure generation (Paw) (40V, 50Hz, 0.2ms).
      Paw was measured at functional residual capacity (FRC) and total lung capacity
      (TLC) as an index of expiratory muscle strength. RESULTS: Paw during spontaneous
      efforts was 20 cmH2O (8.6% predicted). Bipolar (T9-T11) SCS resulted in Paw of 84
      and 103 cmH2O, at FRC and TLC respectively. Monopolar (T9 only) SCS resulted in
      Paw of 61 and 86 cmH2O, at FRC and TLC respectively. This subject experienced
      much greater ease in raising secretions with use of SCS and no longer required
      other methods of secretion management. CONCLUSION: SCS via wire leads, which can
      be implanted using minimally invasive techniques, may provide a new useful method
      to restore an effective cough and possibly reduce the morbidity and mortality
      associated with respiratory tract infections in patients with SCI.

PMID- 29017401
TI  - Helminthosporic acid functions as an agonist for gibberellin receptor.
AB  - Helminthosporol was isolated from a fungus, Helminthosporium sativum, as a
      natural plant growth regulator in 1963. It showed gibberellin-like bioactivity
      that stimulated the growth of the second leaf sheath of rice. After studying the
      structure-activity relationship between the compound and some synthesized
      analogs, it was found that helminthosporic acid (H-acid) has higher gibberellin
      like activity and chemical stability than helminthosporol. In this study, we
      showed that (1) H-acid displays gibberellin-like activities not only in rice but
      also in Arabidopsis, (2) it regulates the expression of gibberellin-related
      genes, (3) it induces DELLA degradation through binding with a gibberellin
      receptor (GID1), and (4) it forms the GID1-(H-acid)-DELLA complex to transduce
      the gibberellin signal in the same manner as gibberellin. This work shows that
      the H-acid mode of action acts as an agonist for gibberellin receptor.

PMID- 29017402
TI  - Validation of two versions of the Warwick-Edinburgh Mental Well-Being Scale among
      Norwegian adolescents.
AB  - AIM: This study aimed to examine the psychometric properties of the original 14
      item version of the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) and the
      short 7-item version (SWEMWBS) to validate these scales for use among Norwegian
      adolescents. METHOD: Cross-sectional data were collected by distributing
      questionnaires among students in five upper secondary schools in Norway with a
      net sample of n = 1814. Exploratory- and confirmatory factor analyses (CFA) and a
      reliability analysis were conducted and possible floor and ceiling effects were
      examined to evaluate the scales. A correlation analysis was conducted to examine
      criterion-related validity. RESULTS: The preliminary exploratory factor analysis
      gave strong indications of a one-dimensional solution for both versions of the
      scale. Furthermore, both scales showed high internal consistency (Cronbach's
      alpha = .93 for the WEMWBS and alpha = .88 for the SWEMWBS). The SWEMWBS showed
      the best fit in the CFA and a strong correlation with the WEMWBS ( r = .94). The
      score distributions of both scales indicated the possibility of a small ceiling
      effect. Both scales showed high correlations with related constructs in the
      expected direction. CONCLUSIONS: In our study, based on the CFA results and the
      high correlation between the original scale and the short version, the SWEMWBS
      was found to be most suitable for use among Norwegian adolescents.

PMID- 29017403
TI  - Protective effect of Zizyphus lotus jujube fruits against cypermethrin-induced
      oxidative stress and neurotoxicity in mice.
AB  - CONTEXT: Cypermethrin (CYP) is a synthetic pyrethroid insecticide used worldwide
      in agriculture, home pest control. The toxicity of CYP is well studied in many
      organisms. OBJECTIVE: The aim of present study was to investigate the protective
      effect of Zizyphus lotus (Zizyp) fruit against neurotoxicity and oxidative stress
      induced by CYP in mice. MATERIALS AND METHODS: Mice were divided into four groups
      of six each: groups I and II were used as control and CYP control (20 mg/kg body
      weight). While, groups III was orally treated with Zizyphus lotus fruit (5 g/kg
      body weight) plus CYP (20 mg/kg body weight) for 18 days. Furthermore, HPLC-ESI
      MS-MS (Q-Tof) and GC-MS were used to identify the compounds fraction. RESULTS:
      Antioxidant enzyme catalase (CAT), neurotoxicity enzyme acetylcholinesterase
      (AChE) activities and hydrogen peroxide (H2O2), malondialdehyde (MDA) levels were
      determined in the liver, kidney and heart. CYP caused decreased CAT activity,
      inhibition of AChE activity and increased the levels of H2O2 and MDA in heart,
      liver and kidney. CONCLUSION: Our results indicate that Zizyp fruit is markedly
      effective in protecting mice against CYP-induced biochemical changes. This
      protection may be due to its antioxidant property and scavenging ability against
      active free radicals.

PMID- 29017404
TI  - Synergistic effect of PANI-ZrO2 composite as antibacterial, anti-corrosion, and
      phosphate adsorbent material: synthesis, characterization and applications.
AB  - The increasing number of bacteria-related problems and presence of trace amounts
      of phosphate in treated wastewater effluents have become a growing concern in
      environmental research. The use of antibacterial agents and phosphate adsorbents
      for the treatment of wastewater effluents is of great importance. In this study,
      the potential applications of a synthesized polyaniline (PANI)-zirconium dioxide
      (ZrO2) composite as an antibacterial, phosphate adsorbent and anti-corrosion
      material were systematically investigated. The results of an antibacterial test
      reveal an effective area of inhibition of 14 and 18 mm for the Escherichia coli
      and Staphylococcus aureus bacterial strains, respectively. The antibacterial
      efficiency of the PANI-ZrO2 composite is twice that of commercial ZrO2. In
      particular, the introduction of PANI increased the specific surface area and
      roughness of the composite material, which was beneficial to increase the contact
      area with bacterial and phosphate. The experimental results demonstrated that
      phosphate adsorption studies using 200 mg P/L phosphate solution showed a
      significant phosphate removal efficiency of 64.4%, and the maximum adsorption
      capacity of phosphate on the solid surface of PANI-ZrO2 is 32.4 mg P/g.
      Furthermore, PANI-ZrO2 coated on iron substrate was tested for anti-corrosion
      studies by a natural salt spray test (7.5% NaCl), which resulted in the formation
      of no rust. To the best of our knowledge, no works have been reported on the
      synergistic effects of the PANI-ZrO2 composite as an antibacterial, anti
      corrosion, and phosphate adsorbent material. PANI-ZrO2 composite is expected to
      be a promising comprehensive treatment method for water filters in the
      aquaculture industry and for use in water purification applications.

PMID- 29017406
TI  - Corrigendum.

PMID- 29017405
TI  - Outcomes of transcatheter aortic valve replacement for bicuspid aortic stenosis -
      a systematic review of existing literature.
AB  - INTRODUCTION: Patients with bicuspid aortic valve (BAV) have traditionally been
      excluded from large randomized clinical trials involving transcatheter aortic
      valve replacements (TAVR). Technical enhancements, availability of new generation
      devices and improved outcomes have led to a marked increase in TAVR volume across
      the world including off label use in patients with BAV stenosis. Areas covered:
      In this manuscript, we have reviewed the currently available data regarding
      safety, efficacy, and outcomes of TAVR in patients with BAV stenosis. 11 large
      observational studies with near 1300 patients with BAV stenosis were included to
      summarizes outcomes of TAVR. Expert Commentary: The present review suggested that
      TAVR may be a safe and feasible treatment modality in BAV stenosis patients. New
      generation devices were associated with high device success rate whereas higher
      adverse procedural events were observed in early generation devices. There are no
      differences in post procedural outcomes with new generation TAVR devices for BAV
      when compared to tricuspid aortic anatomy. Larger studies are needed to evaluate
      the long-term outcome and durability of TAVR in patients with BAV.

PMID- 29017407
TI  - [The relationship between a sense of security and psychological problems in
      adolescents living in boarding schools and youth-welfare institutions].
AB  - Objective: The willingness to participate and a sense of security are important
      aspects to be fostered in the institutional care of adolescents. Although these
      aspects are increasingly being examined from the perspective of the affected
      adolescents, it has yet to be considered whether psychological problems can be
      attributed to their experiences with the above-mentioned aspects. Methods: A
      total of 216 adolescents aged 14 to 18 years answered an online questionnaire the
      sense of security in their institution and their perception of the institution.
      Their willingness to participate was also examined. Psychological symptoms were
      assessed with the Strengths and Difficulties Questionnaire Self-Report (SDQ-S).
      Results: There is a significant correlation between sense of security and the
      overall SDQ score, with prosocial behavior, and with the positive perception of
      the institution. In addition, sense of security had a significant influence on
      the SDQ factors, the positive perception of the institution, and the items on the
      willingness to participate of the adolescents. The subsequent t-tests also showed
      significant results. Among other things, it was shown that the factor problems of
      adolescents is related to sense of security. Conclusion: The results provide an
      initial indication that there is a link between sense of security and
      psychological symptoms as well as willingness to participate and perception of
      the institution. Especially problems of adolescents in dealing with peers must be
      taken into account.in the development of protective concepts to increase the
      sense of security and their willingness to participate.

PMID- 29017408
TI  - Matrix metalloproteinase-2 C-735T and its interaction with matrix
      metalloproteinase-7 A-181G polymorphism are associated with the risk of
      preeclampsia: influence on total antioxidant capacity and blood pressure.
AB  - Matrix metalloproteinase (MMP) -2 C-735 T and MMP-7 A-181 G genotypes were
      studied in 144 pregnant patients with mild and severe preeclampsia and 103
      healthy pregnant women. Significantly higher frequencies of CT and TT genotypes
      in patients compared to controls increased the risk of preeclampsia by 2.42 and
      3.13 times, respectively. In severe preeclamptic women in the presence of MMP-2
      CT the level of total antioxidant capacity was significantly lower than MMP-2 CC
      genotype. Also, in the presence of MMP-2 CT + TT blood pressure was significantly
      increased compared to CC genotype in all the patients. The combined presence of
      MMP-2 T and the MMP-7 A alleles compared to MMP-2 C and MMP-7 A alleles
      significantly increased the risk of preeclampsia by 3.08-fold. Our findings
      demonstrate an association between the MMP-2 C-735 T polymorphism with blood
      pressure and the risk of preeclampsia. Also, in the presence of polymorphism
      total antioxidant capacity level decreased in severe preeclampsia. Impact
      statement What is already known on this subject: Matrix metalloproteinases (MMPs)
      including MMP-2 might be involved in the pathogenesis of preeclampsia through
      alteration of invasive ability of trophoblastic cells and abnormal placentation.
      In one available study the absence of association between MMP-2 C-735T
      polymorphism with gestational hypertension or preeclampsia has been reported.
      What the results of this study add: We found that the presence of MMP-2 C-735T
      polymorphism increased the risk of preeclampsia and there was a significantly
      lower level of total antioxidant capacity in the presence of the polymorphism in
      severe preeclampsia. Also, we found significantly higher systolic and diastolic
      blood pressures in the presence of MMP-2 C-735T polymorphism. We detected a
      synergism between the MMP-2 T and the MMP-7 A alleles that increased the risk of
      preeclampsia. What the implications are of these findings for clinical practice
      and/or further research: New findings of our study are involvement of lower
      activity MMP-2 -735 T allele and its synergism with MMP-7 A allele, low promoter
      activity allele, in the pathogenesis of preeclampsia through possible impairment
      of placentation and also by decreased total antioxidant capacity and increased
      blood pressure. Further association studies of the role of MMP-2 polymorphism and
      MMP-2 activity in relation to oxidative stress parameters and blood pressure
      could elucidate the role of MMP-2 and MMP-7 in the pathogenesis of preeclampsia.

PMID- 29017410
TI  - Effects of Knee Position on the Reliability and Production of Maximal and Rapid
      Strength Characteristics During an Isometric Squat Test.
AB  - This study aimed to examine the effects of knee position on the reliability and
      production of peak force (PF) and rate of force development (RFD) characteristics
      during an isometric squat. Fourteen resistance-trained females performed
      isometric squats at 90, 120, and 150 degrees  knee angles (corresponding to
      parallel, half, and quarter squat positions, respectively) on 2 different
      occasions, from which PF, peak RFD, and early (RFD30, RFD50, RFD100) and late
      (RFD200) phase RFD variables were extracted. PF and RFD200 were highly consistent
      across trials for all 3 squat positions, with intraclass correlation coefficients
      (ICCs) ranging between 0.812-0.904 and coefficients of variation (CVs) between
      6.6-19.4%. For peak and early RFD characteristics, higher ICCs and lower CV
      values were observed for the quarter squat (ICCs = 0.818-0.852, CVs = 17.3-19.4%)
      compared to the parallel (ICCs = 0.591-0.649, CVs = 30.1-55.9%) and half squats
      (ICCs = 0.547-0.598,CVs = 31.1-34.2%). In addition, isometric PF and RFD200
      increased (P <= .001-0.04) with squat position (parallel < half < quarter);
      however, there were no differences for peak RFD (P >= .27), RFD30 (P >= .99),
      RFD50 (P >= .99), and RFD100 (P >= .09). These findings suggest that performing
      isometric squats at higher (150 degrees ) rather than lower knee joint angles (90
      120 degrees ) may provide for an improved capacity to produce greater PF and
      RFD200 as well as a more reliable testing position for measuring peak and early
      RFD characteristics.

PMID- 29017411
TI  - Occult Langerhans Cell Histiocytosis in Clear Cell Renal Cell Carcinoma.
AB  - Langerhans cell histiocytosis is a rare disease that is characterized by a
      localized or systemic proliferation of Langerhans dendritic cells and a wide
      spectrum of clinical presentations. We experienced an unusual case of occult
      Langerhans cell histiocytosis associated with clear cell renal cell carcinoma. A
      62-year-old man underwent a partial nephrectomy for left renal mass. Histologic
      examination showed nests of clear cells with surrounding thin-walled vessel that
      were suggestive of clear cell renal cell carcinoma. A well-defined nodule
      composed of atypical mononuclear cells and plentiful eosinophils presented within
      clear cell renal cell carcinoma. The mononuclear cells were Langerhans cell
      histiocytes with S-100 and CD1a immunoreactivity. On follow-up comprehensive
      physical, laboratory, and radiologic examination, there were no other lesions of
      Langerhans cell histiocytosis.

PMID- 29017415
TI  - Editor's Note.

PMID- 29017409
TI  - Acute Clinical Predictors of Symptom Recovery in Emergency Department Patients
      with Uncomplicated Mild Traumatic Brain Injury or Non-Traumatic Brain Injuries.
AB  - There is a subset of patients with mild traumatic brain injury (mTBI) who report
      persistent symptoms that impair their functioning and quality of life. Being able
      to predict which patients will experience prolonged symptom recovery would help
      clinicians target resources for clinical follow-up to those most in need, and
      would facilitate research to develop precision medicine treatments for mTBI. The
      purpose of this study was to investigate the predictors of symptom recovery in a
      prospective sample of emergency department trauma patients with either mTBI or
      non-mTBI injuries. Subjects were examined at several time points from within 72 h
      to 45 days post-injury. We quantified and compared the value of a variety of
      demographic, injury, and clinical assessment (symptom, neurocognitive) variables
      for predicting self-reported symptom duration in both mTBI (n = 89) and trauma
      control (n = 73) patients. Several injury-related and neuropsychological
      variables assessed acutely (< 72 h) post-injury predicted symptom duration,
      particularly loss of consciousness (mTBI group), acute somatic symptom burden
      (both groups), and acute reaction time (both groups), with reasonably good model
      fit when including all of these variables (area under the receiver operating
      characteristic curve [AUC] = 0.76). Incorporating self-reported litigation
      involvement modestly increased prediction further (AUC = 0.80). The results
      highlight the multifactorial nature of mTBI recovery, and injury recovery more
      generally, and the need to incorporate a variety of variables to achieve adequate
      prediction. Further research to improve this model and validate it in new and
      more diverse trauma samples will be useful to build a neurobiopsychosocial model
      of recovery that informs treatment development.

PMID- 29017416
TI  - Thoughts From a Research Career by Dr Jack H. Dean, the 2017 Mildred S. Christian
      Career Achievement Award Winner.

PMID- 29017417
TI  - Aberrant Expression of lncRNA ( HOXA11-AS1) and Homeobox A ( HOXA9, HOXA10,
      HOXA11, and HOXA13) Genes in Infertile Women With Endometriosis.
AB  - This study aimed to study the expression of homeobox (HOX)A11-AS1 ( HOXA11
      antisense RNA) long noncoding RNA (lncRNA) and the expression of homeobox A (
      HOXA9, HOXA10, HOXA11, and HOXA13) genes in the eutopic (EU) and ectopic (EC)
      endometria of women with peritoneal endometriosis. A total of 30 women undergoing
      laparoscopic surgery for peritoneal endometriosis and 15 infertile women without
      endometriosis were enrolled in this study. Peritoneal EC tissue samples were
      obtained through surgery. The EU tissues were obtained by curettage. The EC and
      EU lncRNA and messenger RNA (mRNA) expression levels were measured using real
      time reverse transcriptase-polymerase chain reaction. The HOXA11-AS1 lncRNA and
      HOXA9, HOXA10, HOXA11, and HOXA13 mRNA were expressed at significantly lower
      levels in the EU than in the EC, that is, in women with peritoneal endometriosis
      ( P < .05). The expression levels of HOXA10 and HOXA11 in the EU were
      significantly lower in women with peritoneal endometriosis compared to the
      control group participants ( P < .05), whereas the levels of lncRNA ( HOXA11
      AS1), HOXA9, and HOXA13 did not differ significantly between the 2 patient groups
      ( P > .05). In conclusion, the study findings suggest that HOXA11-AS1 lncRNA may
      play a role in the development of peritoneal endometriosis, but HOXA11-AS1 may
      not influence endometrial receptivity in endometriosis-associated infertility.

PMID- 29017420
TI  - Attitudes to evolution among Christians, Muslims and the Non-Religious in
      Britain: Differential effects of religious and educational factors.
AB  - According to poll results and media reports, Britain has a significant and
      growing number of creationists. However, little scholarly research has been
      carried out to explore this phenomenon. We present results from a national survey
      of 6020 individuals to give a comprehensive picture of contemporary public
      attitudes to evolution in Britain. Furthermore, we explore the effects of
      religion and education on attitudes to evolution. Unique to this study, we
      analyse the effects of attending a religiously affiliated school ('faith school')
      on acceptance of evolutionary theory. We examine these effects in the general
      population, and additionally, across different Christian, Muslim and Non
      Religious subpopulations. Results give strong evidence that the number of
      creationists has been overstated previously. We find the effect of education is
      complex and varies between different religious groups, but that faith school
      attendance is associated with more acceptance of evolution for people belonging
      to groups that tend to reject it.

PMID- 29017418
TI  - Maternal Glucose Supplementation in a Murine Model of Chorioamnionitis Alleviates
      Dysregulation of Autophagy in Fetal Brain.
AB  - Fetal brain injury induced by intrauterine inflammation is a major risk factor
      for adverse neurological outcomes, including cerebral palsy, cognitive
      dysfunction, and behavioral disabilities. There are no adequate therapies for
      neuronal protection to reduce fetal brain injury, especially new strategies that
      may apply promptly and conveniently. In this study, we explored the effect of
      maternal glucose administration in a mouse model of intrauterine inflammation at
      term. Our results demonstrated that maternal glucose supplementation
      significantly increased survival birth rate and improved the neurobehavioral
      performance of pups exposed to intrauterine inflammation. Furthermore, we
      demonstrated that maternal glucose administration improved myelination and
      oligodendrocyte development in offspring exposed to intrauterine inflammation.
      Though the maternal blood glucose concentration was temporally prevented from
      decrease induced by intrauterine inflammation, the glucose concentration in fetal
      brain was not recovered by maternal glucose supplementation. The adenosine
      triphosphate (ATP) level and autophagy in fetal brain were regulated by maternal
      glucose supplementation, which may prevent dysregulation of cellular metabolism.
      Our study is the first to provide evidence for the role of maternal glucose
      supplementation in the cell survival of fetal brain during intrauterine
      inflammation and further support the possible medication with maternal glucose
      treatment.

PMID- 29017421
TI  - Access to Medical Records' Impact on Community Pharmacist-Delivered Medication
      Therapy Management: A Pilot From the Medication Safety Research Network of
      Indiana (Rx-SafeNet).
AB  - BACKGROUND: Medication therapy management (MTM) may be optimized if pharmacists
      engaged in health information exchange (HIE) by reviewing unedited medical
      records. METHODS: In this nonblinded, randomized, controlled pilot, pharmacists
      delivered a part of MTM, comprehensive medication reviews (CMRs), to adult
      patients in a practice-based research network (PBRN). Intervention community
      pharmacists solicited the last 6 months of patients' primary care provider-held,
      unedited medical records. The primary and secondary outcomes were the number of
      medication-related problems (MRPs) and preventive care omissions identified. The
      intervention was analyzed via Mann-Whitney U test and multivariate linear
      regression models. Pharmacists were surveyed regarding the available health
      history's helpfulness in CMR delivery. RESULTS: Thirty-seven patients received
      CMRs across the 2 groups. Intervention pharmacists (n = 4) identified
      significantly more MRPs (median = 11 vs 6; B = 6.98, 95% confidence interval
      [CI]: 0.005-13.96; P = .049) and omissions in preventive care (24% vs 17%; B =
      2.78, 95% CI: 0.46-5.10; P = .009) than usual care pharmacists (n = 3).
      Intervention pharmacists were more likely to agree they were confident they
      identified all of the patient's MRPs (47.1% vs 15.8%), but neither group was more
      likely than the other to believe they had resolved all MRPs (41.2% vs 42.1%).
      Finally, intervention pharmacists agreed 100% of the time that the available
      health history helped them complete a better CMR, compared with only 69% of usual
      care pharmacists. CONCLUSION: In this pilot, community pharmacists identified
      more MRPs and omissions in preventive care when they reviewed unedited medical
      records. Larger studies are warranted to determine whether HIE can improve
      outcomes.

PMID- 29017419
TI  - Effect of Normal Pregnancy Followed by Lactation on Long-Term Maternal Health in
      a Mouse Model.
AB  - Although it has been widely accepted that pregnancies with complications are
      associated with increased maternal cardiovascular risk later in life, there is no
      consensus if noncomplicated pregnancy followed by lactation plays a protective
      role or is a risk factor. The objective of this study was to investigate the
      effects of normal pregnancy and lactation on long-term maternal health in a mouse
      model. CD-1 mice were allocated to breeding (primigravid [PG]) and nonbreeding
      (nulligravid [NG]) groups. The PG group proceeded through normal pregnancy and
      delivery. Using a telemetry system, blood pressure (BP) was analyzed in the PG
      group at 6 months postpartum and in age-matched NG mice. Serum analytes, gene
      expressions, and protein levels were determined using appropriate analysis
      methods. Primigravid mice had significantly lower systolic and diastolic BP and
      fasting glucose levels. Circulating oxytocin (OXT) levels were significantly
      higher in PG mice. Oxt gene expression was significantly higher in the heart and
      aorta and lower in visceral adipose tissue (VAT) from PG mice. The oxytocin
      receptor ( Oxtr) gene expression was significantly higher in the heart, aorta,
      and VAT from PG animals. The level of Oxtr DNA hypermethylation and the
      expression of mmu-miR-29a were significantly lower in the hearts of PG mice. In
      PG VAT, glucose transporter-4 expression was significantly higher. Our study
      demonstrates that a history of normal pregnancy followed by lactation was
      associated with lower maternal cardiovascular risk factors later in life in
      female mouse.

PMID- 29017422
TI  - Nintedanib for Idiopathic Pulmonary Fibrosis.
AB  - OBJECTIVE: To review the pharmacology, safety, and efficacy of nintedanib for the
      treatment of idiopathic pulmonary fibrosis (IPF). METHODS: A literature search
      was conducted via PubMed using the MeSH term "idiopathic pulmonary fibrosis"
      combined with the key word "nintedanib." Additional online searches using Google
      Scholar, Micromedex, and PubMed were performed to obtain prescribing and cost
      information. RESULTS: One phase II and 2 replicate phase III clinical trials that
      examined the safety and efficacy of nintedanib for IPF were identified. In
      patients with IPF, nintedanib was more effective than placebo in slowing the
      annual rate of decline in forced vital capacity (FVC). Improvements in mortality,
      quality of life, and risk of acute exacerbations have not been consistently
      demonstrated in clinical trials. Diarrhea was the most common adverse effect
      associated with nintedanib use. Outside of these clinical trials, there are
      limited data evaluating nintedanib for the treatment of IPF. CONCLUSIONS:
      Nintedanib is a safe and effective treatment option for patients with IPF.
      Nintedanib slows IPF disease progression by reducing the rate of decline in FVC.
      Reductions in mortality and acute exacerbations may be present in certain
      subgroups of patients, but these outcomes require further research. Future
      studies on nintedanib are needed to explore its use in more advanced stages of
      IPF, its long-term safety and efficacy, its value in combination with pirfenidone
      or other therapies for IPF, and its cost-effectiveness in clinical practice.

PMID- 29017423
TI  - Utilization of an Integrated Electronic Health Record in the Emergency Department
      to Increase Prospective Medication Order Review by Pharmacists.
AB  - PURPOSE: The objective of this study is to evaluate the impact of an integrated
      medical record system on prospective medication order verification by pharmacists
      in the emergency department (ED) of a level I trauma center. METHODS: This was a
      single-center retrospective analysis comparing medication orders verified by a
      pharmacist during a 7-day period in 2013 (phase I) versus 2015 (phase II).
      Outcome measures include the percentage of medication orders reviewed by a
      pharmacist prior to administration and time from order entry to each of the
      following: pharmacist review, medication procurement from an automated dispensing
      cabinet (ADC), and medication administration. RESULTS: In total, 5450 medication
      orders were included in the study. The percentage of medication orders reviewed
      by a pharmacist prior to administration increased from 51.8% to 94% in phase I
      versus phase II, respectively ( P < .001). Median time from order entry to
      pharmacist verification decreased from 13 to 4 minutes in phase I versus phase
      II, respectively ( P < .001). Time from order entry to ADC dispense increased
      from a median of 9 minutes in phase I to 15 minutes in phase II ( P < .001). Time
      from order entry to nursing administration increased from a median time of 15
      minutes in phase I to 23 minutes in phase II ( P < .001). CONCLUSION:
      Implementation of prospective pharmacist order verification in the ED increased
      the percentage of medications reviewed by a pharmacist prior to administration
      and improved pharmacist efficiency in the medication verification process. This
      increase in pharmacist review was associated with a marginal increase in time to
      medication procurement and administration.

PMID- 29017424
TI  - Development of a Statewide Antibiogram to Assess Regional Trends in Antibiotic
      Resistant ESKAPE Organisms.
AB  - BACKGROUND: Hospitals and other facilities utilize antibiograms as tools for
      optimal antibiotic selection. Currently, no measures compare broad trends on the
      regional level, despite interest for more comprehensive data, particularly for
      antibiotic-resistant ESKAPE organisms. OBJECTIVE: To collect and compare regional
      health-care facility antibiogram data for ESKAPE organisms to form a cumulative
      antibiogram. METHODS: Health-care facilities were identified using the publicly
      accessible Pennsylvania Department of Health web site. Facilities were contacted
      by phone from June 2015 to 2016 to ascertain participation/consent for the study.
      An electronic questionnaire ascertained baseline facility characteristics.
      Facilities provided quantitative antibiotic susceptibility data via antibiograms.
      Antibiogram data were synthesized as cumulative susceptibilities, stratified by
      urban/suburban versus rural location. RESULTS: Forty-five facilities were
      included in the study (n = 18 urban/suburban, n = 27 rural). The overall
      prevalence of methicillin-resistant S aureus was 41.5%, stratified at 40.6% and
      43.3% in urban/suburban and rural facilities, respectively ( P < .001).
      Vancomycin-resistant Enterococcus prevalence was 18.8% overall, with 27.7% in
      urban/suburban and 14.0% in rural facilities ( P < .001). Generally, lower
      susceptibility rates were found for high-utilization beta-lactams across gram
      negative organisms in urban/suburban facilities. CONCLUSIONS: Development of a
      regional cumulative antibiogram that targets key ESKAPE pathogens is feasible,
      while observed trends may help aid future antimicrobial stewardship efforts.

PMID- 29017425
TI  - Time to Occurrence Based on Risk Stratification of Hospital-Acquired Venous
      Thromboembolism: A Retrospective Observational Cohort Study.
AB  - BACKGROUND: In-hospital venous thromboembolism (VTE) causes significant morbidity
      and mortality in hospitalized patients. The objective of our study is to
      determine the time to in-hospital VTE based on baseline risk stratification.
      METHODS: All adult patients admitted to a 900-bed academic tertiary referral
      hospital who developed a VTE during hospital admission from September 1, 2011, to
      June 30, 2015, were retrospectively analyzed. Patients were excluded if they were
      younger than 18 years or if the VTE was present on admission. RESULTS: The cohort
      included 400 patients, 224 (56%) males, median age 66 years. The median time to
      VTE was 8 days. Significant differences in time to VTE existed between the risk
      groups. CONCLUSION: Time to VTE in a broad hospitalized patient population
      differs based on admission risk group. This finding highlights the importance of
      performing risk assessment upon admission and subsequently with clinical changes
      to assess increases in risk scores.

PMID- 29017426
TI  - Investigations on the Influence of Zidovudine in the Pharmacokinetics of
      Isoniazid and Its Hepatotoxic Metabolites in Rats.
AB  - The HIV-infected patients are co-infected with many bacterial infections in which
      tuberculosis is most common found worldwide. These patients are often
      administered with combined therapy of anti-retroviral and anti-tubercular drugs
      which leads to several complications including hepatotoxicity or adverse drug
      interactions. The drug-drug interactions between the anti-retroviral and anti
      tubercular drugs are not clearly defined and hence, this study was conducted to
      evaluate the pharmacokinetic drug-drug interactions of Zidovudine (AZT) with
      Isoniazid (INH) and its hepatotoxic metabolites. Seventy two rats were randomly
      divided into two major groups with their sub-groups each comprising 6 animals.
      The Group I received INH alone at a dose of 25 mg/kg; b.w and Group II received
      AZT (50 mg/kg; b.w) along with INH orally. Pharmacokinetic studies of INH and its
      metabolites i.e., acetyl hydrazine (ACHY) and hydrazine (HYD) shows that INH and
      ACHY attains maximum plasma concentration ( Cmax) within 30 minutes and HYD
      attains Cmax at 1 hour after INH administration and all these analytes disappear
      from plasma within 4 hours. Pharmacokinetic studies also revealed that AZT
      treatment did not showed any drug-drug interactions and have no effect on the
      T1/2, plasma clearance, AUC, Cmax and Tmax of INH and its hepatotoxic
      metabolites.

PMID- 29017428
TI  - Editor Farewell.

PMID- 29017427
TI  - Fraction Intervention for Students With Mathematics Difficulties: Lessons Learned
      From Five Randomized Controlled Trials.
AB  - In this article, the authors summarize results from 5 randomized controlled
      trials assessing the effects of intervention to improve the fraction performance
      of fourth-grade students at risk for difficulty in learning about fractions. The
      authors begin by explaining the importance of competence with fractions and why
      an instructional focus on fractions magnitude understanding may improve learning.
      They then describe an intervention that relies strongly on this type of
      understanding about fractions instruction, and they provide an overview of the
      intervention's overall effects. This is followed by an overview of 5 intervention
      components for which the authors isolated effects. They conclude by discussing
      some of the lessons learned from this research program.

PMID- 29017429
TI  - Rehabilitation methods for reducing shoulder subluxation in post-stroke
      hemiparesis: a systematic review.
AB  - Background Shoulder subluxation is a common post-stroke complication affecting up
      to 80% of the stroke subjects. The pathomechanics at the skeletal level does not
      provide the structural base for the neural-motor recovery. The management of
      subluxed shoulder has always been a challenge, complicating the motor and
      functional recovery. Objective To review the available studies of rehabilitation
      interventions for reduction of subluxed shoulder and to explore the evidence for
      impact of subluxation on motor recovery. Method PubMed, the Cochrane Central
      Register of Controlled Trials, DORIS, PEDro, and OTseeker databases were searched
      using the keywords: Stroke and Shoulder and Subluxation. The experimental, quasi
      experimental, and single group studies investigated the rehabilitation methods to
      reduce the subluxation were selected. A narrative synthesis of the findings from
      the selected studies was carried out. Result 2717 studies were identified and 22
      studies (14 RCTs or controlled trials and 8 pre-post-single group studies) were
      finally selected for the review. The rehabilitation intervention: Functional
      electrical stimulation (FES)/electrical stimulation (11), orthosis/support (07),
      taping (02), and robotic training and other methods (02) were reviewed. FES is
      effective in reducing subluxation in acute stage. Shoulder support or orthosis
      while in situ may reduce the subluxation temporarily. X-ray was the most commonly
      used assessment tool for the subluxation. Implication of the rehabilitation
      technique on motor recovery has not been investigated. Conclusion No technique
      could effectively reduce the subluxation and facilitate the upper limb recovery.
      Further studies integrating the usual motor training and the subluxation
      rehabilitation are warranted. Future trials using more precise and valid tool
      such as ultrasonography are also needed.

PMID- 29017433
TI  - The Measurement, Challenges, and Opportunities of Decisional Involvement.

PMID- 29017430
TI  - Characterizing neurocognitive late effects in childhood leukemia survivors using
      a combination of neuropsychological and cognitive neuroscience measures.
AB  - Knowledge about cognitive late effects in survivors of childhood acute
      lymphoblastic leukemia (ALL) is largely based on standardized neuropsychological
      measures and parent reports. To examine whether cognitive neuroscience paradigms
      provided additional insights into neurocognitive and behavioral late effects in
      ALL survivors, we assessed cognition and behavior using a selection of cognitive
      neuroscience tasks and standardized measures probing domains previously
      demonstrated to be affected by chemotherapy. 130 ALL survivors and 158 control
      subjects, between 8 and 18 years old at time of testing, completed the n-back
      (working memory) and stop-signal (response inhibition) tasks. ALL survivors also
      completed standardized measures of intelligence (Wechsler Intelligence Scales
      [WISC-IV]), motor skills (Grooved Pegboard), math abilities (WIAT-III), and
      executive functions (Delis-Kaplan Executive Function System). Parents completed
      behavioral measures of executive functions (Behavior Rating Inventory of
      Executive Function [BRIEF]) and attention (Conners-3). ALL survivors exhibited
      deficiencies in working memory and response inhibition compared with controls.
      ALL survivors also exhibited deficits on WISC-IV working memory and processing
      speed, Grooved Pegboard, WIAT-III addition and subtraction fluency, and numerical
      operations, as well as DKEFS number-letter switching. Parent reports suggested
      more attention deficits (Conners-3) and behavioral difficulties (BRIEF) in ALL
      survivors compared with referenced norms. Low correspondence between standardized
      and experimental measures of working memory and response inhibition was noted.
      The use of cognitive neuroscience paradigms complements our understanding of the
      cognitive deficits evident after treatment of ALL. These measures could further
      delineate cognitive processes involved in neurocognitive late effects, providing
      opportunities to explore their underlying mechanisms.

PMID- 29017432
TI  - Ectopic expression of Mesembryanthemum crystallinum sodium transporter McHKT2
      provides salt stress tolerance in Arabidopsis thaliana.
AB  - Most plants do not tolerate highly saline environments; the development of salt
      stress tolerance is crucial for improving crop yield. An efficient way of finding
      genes involved in salt tolerance is to study and use data from halophytes. In
      this study, we used the Mesembryanthemum crystallinum (ice plant) expression data
      set and selected for further study the gene McHKT2, which encodes for the
      Arabidopsis sodium transporter ortholog AtHKT1. In comparison with the HKT1 amino
      acid sequences from other plants, McHKT2 has several unique features. It seems to
      be localized to the plasma membrane, and its overexpression confers strong salt
      tolerance in Arabidopsis thaliana. Our results indicate that McHKT2 is a suitable
      candidate protein that can induce salt tolerance in non-halophytes. Like McHKT2,
      using transcriptome data-sets from halophytes such as ice plant give us an
      efficiency way to obtain new gene resources that might involve in plant salt
      tolerance.

PMID- 29017434
TI  - Transesophageal Echocardiogram-Guided Stent Placement in Superior Vena Cava
      Syndrome Secondary to Granulomatous Lung Disease: A Case Series and Literature
      Review.
AB  - Obstruction of the superior vena cava (SVC) is an uncommon, but potentially life
      threatening condition due to likely development of edema in the head and neck and
      potential respiratory compromise. Less than half of those affected by SVC
      syndrome survive more than a year. Obstruction can be from neoplasms or secondary
      to benign disease. Treatment for most cases of symptomatic SVC syndrome involves
      placement of a stent to relieve the stenosis. Serious complications such as stent
      migration, pulmonary embolism, and cardiac tamponade can occur in 5% to 10% of
      cases, and inadequate imaging of the SVC-atrial junction by fluoroscopy
      contributes to these problems. The overlapping contrast in the atrium makes it
      difficult to precisely place the distal end of the stent, potentially allowing
      for embolization of the stent to occur. We present a case series of 3 patients
      wherein transesophageal echocardiography was used for guidance of stent placement
      in the SVC and significantly aided in placement.

PMID- 29017435
TI  - Expression, purification, and characterization of a novel acid phosphatase that
      displays protein tyrosine phosphatases activity from Metarhizium anisopliae
      strain CQMa102.
AB  - The protein tyrosine phosphatase (PTPase) plays an important role in insect
      immune system. Our group has purified a type of acid phosphatase that could
      specifically dephosphorylate trans-Golgi p230 in vitro. In order to study this
      phosphatase further, we have identified and cloned the phosphatase gene from a
      locust specific Metarhizium anisopliae Strain CQMa102. The CQMa102 phosphatase
      was expressed in Pichia pastoris to verify its protease activity. The molecular
      weight (MW) and the isoelectric point (pI) of the phosphatase were about 85 kDa
      and 6.15, respectively. Substrate specificity evaluation showed that the purified
      enzyme exhibited high activity on O-phospho-L-tyrosine. At its optimal pH of 6.5
      and optimum temperature of 70  degrees C, the protein showed the highest activity
      respectively. It can be activated by Ca2+, Mg2+, Mn2+, Ba2+, Co2+ and phosphate
      analogs, but inhibited by Zn2+, Cu2+, fluoride, dithiothreitol, beta
      mercaptoethanol and N-ethylmaleimide.

PMID- 29017436
TI  - Role of Markov Modeling Approaches to Understand the Impact of Infertility
      Treatments.
AB  - We are proposing to use Markov modeling type of analysis to understand data
      generated by treatments for infertility in women receiving ovarian stimulations.
      We describe the conceptual novelties, need for such an analysis, basics of the
      proposed methods, and theoretical constructions of various probabilities
      associated with practical level implementation of the Markov modeling procedures.
      This method can be adopted to infertility-related data visualizations whenever
      progression of outcome stages in infertility treatment is recorded. These methods
      if implemented should be able to enhance the understanding of treatment impacts
      of gonadotropins, clomiphene citrate, or an aromatase inhibitor at the beginning
      of treatment cycles of infertile women. This framework will be very useful for
      infertility treatment practitioners to compute the values of success rates of
      treatment for total population or population divided by demographic, clinical,
      and genetic factors. These methods can be continuously updated with newer data
      and translated into a mobile app to be used by clinical practitioners.

PMID- 29017437
TI  - High Expression of High-Mobility Group Box 1 in Menstrual Blood: Implications for
      Endometriosis.
AB  - Endometriosis is a benign gynecologic disease characterized by the presence of
      ectopic endometrium and associated with inflammation and immune abnormalities.
      However, the molecular basis for endometriosis is not well understood. To address
      this issue, the present study examined the expression of high-mobility group box
      (HMGB) 1 in menstrual blood to investigate its role in the ectopic growth of
      human endometriotic stromal cells (ESCs). A total of 139 patients were enrolled
      in this study; 84 had endometriosis and 55 were nonendometriotic gynecological
      patients (control). The HMGB1 levels in various fluids were measured by enzyme
      linked immunosorbent assay. Expression of receptor for advanced glycation end
      products (RAGE) in eutopic and ectopic endometrium was assessed by
      immunohistochemistry, and RAGE and vascular endothelial growth factor ( VEGF)
      messenger RNA expression in HMGB1- and lipopolysaccharide (LPS)-treated ESCs was
      evaluated by real-time polymerase chain reaction. The HMGB1 concentration was
      higher in menstrual blood than in serum or peritoneal fluid ( P < .001 for both).
      RAGE was expressed in both normal and ectopic endometrium. Administration of 1000
      ng/mL HMGB1 or coadministration of 100 ng/mL HMGB1 and 100 ng/mL LPS induced VEGF
      production in ESCs relative to the control ( P < .05). These results suggest that
      menstrual fluid has naturally high levels of HMGB1 and may promote endometriosis
      following retrograde menstruation when complexed with other factors such as LPS
      by inducing inflammation and angiogenesis.

PMID- 29017440
TI  - Epigenetic Role in Hypertensive Disorders of Pregnancy.

PMID- 29017441
TI  - Midwest Nursing Research Society News.

PMID- 29017438
TI  - HSD11B2, RUNX3, and LINE-1 Methylation in Placental DNA of Hypertensive Disorders
      of Pregnancy Patients.
AB  - Hypertensive Disorders of Pregnancy (HDsP) remain leading causes of maternal and
      perinatal morbidity and mortality. Growing evidence suggests the involvement of
      epigenetic factors, such as gene-specific and global DNA methylation changes,
      both in the etiology and as an effect of HDsP. In this study, we investigated the
      potential association between placental DNA methylation status in selected CpGs
      of HSD11B2 cortisol level controlling gene, RUNX3 tumor suppressor gene, and long
      interspersed nucleotide element-1 (LINE-1) repetitive elements and HDsP
      preeclampsia (PE), gestational hypertension (GH), and chronic hypertension (CH).
      Methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PSQ)
      were used to analyze placental DNA methylation. Plasma and urine cortisol and
      cortisone levels were measured using high performance liquid chromatography with
      fluorescence detection (HPLC-FLD), whereas serum progesterone level was
      determined by electrochemiluminescence immunoassay. The mean percentage of
      HSD11B2, RUNX3, and LINE-1 methylation was not altered in the placentas of
      patients with HDsP, as compared to the controls. However, among patients from PE,
      GH, and CH groups, several significant correlations were observed between the
      methylation status of HSD11B2, RUNX3, or LINE-1 and children's birth weight,
      gestational age at delivery, mother's age, and body mass index as well as
      hormones levels. These results indicate lack of association between methylation
      status of HSD11B2, RUNX3, or LINE-1 repetitive elements and HDsP. However,
      association of these parameters with some clinical variables may suggest the role
      of placental DNA methylation in fetal development and should be further explored.

PMID- 29017439
TI  - The Expression of PDCD4 in Patients With Missed Abortion and Its Clinical
      Significance.
AB  - Missed abortion is a special form of spontaneous abortion and its incidence shows
      a rising trend. Immunological factor is one of the most common reasons. Tumor
      suppressor gene programmed cell death 4 ( PDCD4) also participates in some immune
      mediated inflammation, such as atherosclerosis, and so on, but the role of PDCD4
      in missed abortion remains unclear. Here, the expression of PDCD4 was detected in
      decidual and chorionic tissues, as well as peripheral blood mononuclear cells
      from patients with missed abortion and healthy controls using quantitative real
      time polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry.
      The expression of cytokines was also detected in decidual tissues using qRT-PCR.
      The levels of serum estradiol and progesterone were measured by radioimmunoassay.
      In addition, the correlations of PDCD4 expression with cytokines and hormones
      were analyzed. The results demonstrated that PDCD4 expression was reduced in
      decidual tissues from the missed abortion group compared with the control group.
      The levels of tumor necrosis factor alpha were significantly higher in decidual
      tissues of missed abortion patients than those in normal controls. We also found
      serum estradiol and progesterone levels were significantly lower in the missed
      abortion group than those in the control group, and serum progesterone level was
      inversely related to PDCD4 messenger RNA level. The data suggested that reduced
      PDCD4 expression may be involved in the occurrence of missed abortion. This may
      facilitate the potential development of novel diagnostic and therapeutic
      strategies for the treatment of missed abortion.

PMID- 29017443
TI  - A new synonym-substitution method to enrich the human phenotype ontology.
AB  - BACKGROUND: Named entity recognition is critical for biomedical text mining,
      where it is not unusual to find entities labeled by a wide range of different
      terms. Nowadays, ontologies are one of the crucial enabling technologies in
      bioinformatics, providing resources for improved natural language processing
      tasks. However, biomedical ontology-based named entity recognition continues to
      be a major research problem. RESULTS: This paper presents an automated synonym
      substitution method to enrich the Human Phenotype Ontology (HPO) with new
      synonyms. The approach is mainly based on both the lexical properties of the
      terms and the hierarchical structure of the ontology. By scanning the lexical
      difference between a term and its descendant terms, the method can learn new
      names and modifiers in order to generate synonyms for the descendant terms. By
      searching for the exact phrases in MEDLINE, the method can automatically rule out
      illogical candidate synonyms. In total, 745 new terms were identified. These
      terms were indirectly evaluated through the concept annotations on a gold
      standard corpus and also by document retrieval on a collection of abstracts on
      hereditary diseases. A moderate improvement in the F-measure performance on the
      gold standard corpus was observed. Additionally, 6% more abstracts on hereditary
      diseases were retrieved, and this percentage was 33% higher if only the highly
      informative concepts were considered. CONCLUSIONS: A synonym-substitution
      procedure that leverages the HPO hierarchical structure works well for a reliable
      and automatic extension of the terminology. The results show that the generated
      synonyms have a positive impact on concept recognition, mainly those synonyms
      corresponding to highly informative HPO terms.

PMID- 29017442
TI  - Genome-wide characterization, evolution, and expression analysis of the leucine
      rich repeat receptor-like protein kinase (LRR-RLK) gene family in Rosaceae
      genomes.
AB  - BACKGROUND: Leucine-rich repeat receptor-like protein kinase (LRR-RLK) is the
      largest gene family of receptor-like protein kinases (RLKs) and actively
      participates in regulating the growth, development, signal transduction,
      immunity, and stress responses of plants. However, the patterns of LRR-RLK gene
      family evolution in the five main Rosaceae species for which genome sequences are
      available have not yet been reported. In this study, we performed a comprehensive
      analysis of LRR-RLK genes for five Rosaceae species: Fragaria vesca (strawberry),
      Malus domestica (apple), Pyrus bretschneideri (Chinese white pear), Prunus mume
      (mei), and Prunus persica (peach), which contained 201, 244, 427, 267, and 258
      LRR-RLK genes, respectively. RESULTS: All LRR-RLK genes were further grouped into
      23 subfamilies based on the hidden Markov models approach. RLK-Pelle_LRR-XII-1,
      RLK-Pelle_LRR-XI-1, and RLK-Pelle_LRR-III were the three largest subfamilies.
      Synteny analysis indicated that there were 236 tandem duplicated genes in the
      five Rosaceae species, among which subfamilies XII-1 (82 genes) and XI-1 (80
      genes) comprised 68.6%. CONCLUSIONS: Our results indicate that tandem duplication
      made a large contribution to the expansion of the subfamilies. The gene
      expression, tissue-specific expression, and subcellular localization data
      revealed that LRR-RLK genes were differentially expressed in various organs and
      tissues, and the largest subfamily XI-1 was highly expressed in all five Rosaceae
      species, suggesting that LRR-RLKs play important roles in each stage of plant
      growth and development. Taken together, our results provide an overview of the
      LRR-RLK family in Rosaceae genomes and the basis for further functional studies.

PMID- 29017444
TI  - Quantitative trait loci associated with different polar metabolites in perennial
      ryegrass - providing scope for breeding towards increasing certain polar
      metabolites.
AB  - BACKGROUND: Recent advances in the mapping of biochemical traits have been
      reported in Lolium perenne. Although the mapped traits, including individual
      sugars and fatty acids, contribute greatly towards ruminant productivity, organic
      acids and amino acids have been largely understudied despite their influence on
      the ruminal microbiome. RESULTS: In this study, we used a targeted gas
      chromatography mass spectrometry (GC-MS) approach to profile the levels of 25
      polar metabolites from different classes (sugars, amino acids, phenolic acids,
      organic acids and other nitrogen-containing compounds) present in a L. perenne F2
      population consisting of 325 individuals. A quantitative trait (QTL) mapping
      approach was applied and successfully identified QTLs regulating seven of those
      polar metabolites (L-serine, L-leucine, glucose, fructose, myo-inositol, citric
      acid and 2, 3-hydroxypropanoic acid).Two QTL mapping approaches were carried out
      using SNP markers on about half of the population only and an imputation approach
      using SNP and DArT markers on the entire population. The imputation approach
      confirmed the four QTLs found in the SNP-only analysis and identified a further
      seven QTLs. CONCLUSIONS: These results highlight the potential of utilising
      molecular assisted breeding in perennial ryegrass to modulate a range of
      biochemical quality traits with downstream effects in livestock productivity and
      ruminal digestion.

PMID- 29017445
TI  - Protein remote homology detection based on bidirectional long short-term memory.
AB  - BACKGROUND: Protein remote homology detection plays a vital role in studies of
      protein structures and functions. Almost all of the traditional machine leaning
      methods require fixed length features to represent the protein sequences.
      However, it is never an easy task to extract the discriminative features with
      limited knowledge of proteins. On the other hand, deep learning technique has
      demonstrated its advantage in automatically learning representations. It is
      worthwhile to explore the applications of deep learning techniques to the protein
      remote homology detection. RESULTS: In this study, we employ the Bidirectional
      Long Short-Term Memory (BLSTM) to learn effective features from pseudo proteins,
      also propose a predictor called ProDec-BLSTM: it includes input layer,
      bidirectional LSTM, time distributed dense layer and output layer. This neural
      network can automatically extract the discriminative features by using
      bidirectional LSTM and the time distributed dense layer. CONCLUSION: Experimental
      results on a widely-used benchmark dataset show that ProDec-BLSTM outperforms
      other related methods in terms of both the mean ROC and mean ROC50 scores. This
      promising result shows that ProDec-BLSTM is a useful tool for protein remote
      homology detection. Furthermore, the hidden patterns learnt by ProDec-BLSTM can
      be interpreted and visualized, and therefore, additional useful information can
      be obtained.

PMID- 29017446
TI  - LSTrAP: efficiently combining RNA sequencing data into co-expression networks.
AB  - BACKGROUND: Since experimental elucidation of gene function is often laborious,
      various in silico methods have been developed to predict gene function of
      uncharacterized genes. Since functionally related genes are often expressed in
      the same tissues, conditions and developmental stages (co-expressed), functional
      annotation of characterized genes can be transferred to co-expressed genes
      lacking annotation. With genome-wide expression data available, the construction
      of co-expression networks, where genes are nodes and edges connect significantly
      co-expressed genes, provides unprecedented opportunities to predict gene
      function. However, the construction of such networks requires large volumes of
      high-quality data, multiple processing steps and a considerable amount of
      computation power. While efficient tools exist to process RNA-Seq data, pipelines
      which combine them to construct co-expression networks efficiently are currently
      lacking. RESULTS: LSTrAP (Large-Scale Transcriptome Analysis Pipeline), presented
      here, combines all essential tools to construct co-expression networks based on
      RNA-Seq data into a single, efficient workflow. By supporting parallel computing
      on computer cluster infrastructure, processing hundreds of samples becomes
      feasible as shown here for Arabidopsis thaliana and Sorghum bicolor, which
      comprised 876 and 215 samples respectively. The former was used here to show how
      the quality control, included in LSTrAP, can detect spurious or low-quality
      samples. The latter was used to show how co-expression networks are able to group
      known photosynthesis genes and imply a role in this process of several, currently
      uncharacterized, genes. CONCLUSIONS: LSTrAP combines the most popular and
      performant methods to construct co-expression networks from RNA-Seq data into a
      single workflow. This allows large amounts of expression data, required to
      construct co-expression networks, to be processed efficiently and consistently
      across hundreds of samples. LSTrAP is implemented in Python 3.4 (or higher) and
      available under MIT license from https://github.molgen.mpg.de/proost/LSTrAP.

PMID- 29017447
TI  - Characterization of a novel KCNJ2 sequence variant detected in Andersen-Tawil
      syndrome patients.
AB  - BACKGROUND: Mutations in the KCNJ2 gene encoding the ion channel Kir2.1 have been
      linked to the Andersen-Tawil syndrome (ATS). Molecular genetic screening
      performed in a family exhibiting clinical ATS phenotypes unmasked a novel
      sequence variant (c.434A > G, p.Y145C) in this gene. The aim of this study was to
      investigate the effect of this variant on Kir2.1 ion channel functionality.
      METHODS: Mutant as well as wild type GFP tagged Kir2.1 channels were expressed in
      HEK293 cells. In order to examine the effect of the new variant,
      electrophysiological measurements were performed using patch clamp technique.
      Cellular localization of the mutant in comparison to the wild type ion channel
      was analyzed by confocal laser scanning microscopy. RESULTS: The currents of
      cells expressing only mutant channels or a mixture of wild type and mutant were
      significantly reduced compared to those expressing wild type (WT) channels (p <
      0.01). Whereas WT expressing cells exhibited at -120 mV an averaged current of 
      4.5 +/- 1.9 nA, the mutant generates only a current of -0.17 +/- 0.07 nA. A co
      expression of mutant and WT channel generates only a partial rescue of the WT
      current. Confocal laser scanning microscopy indicated that the novel variant is
      not interfering with synthesis and/or protein trafficking. CONCLUSIONS: The
      detected sequence variant causes loss-of-function of the Kir2.1 channel and
      explains the clinical phenotypes observed in Andersen-Tawil syndrome patients.

PMID- 29017448
TI  - What is polypharmacy? A systematic review of definitions.
AB  - BACKGROUND: Multimorbidity and the associated use of multiple medicines
      (polypharmacy), is common in the older population. Despite this, there is no
      consensus definition for polypharmacy. A systematic review was conducted to
      identify and summarise polypharmacy definitions in existing literature. METHODS:
      The reporting of this systematic review conforms to the Preferred Reporting Items
      for Systematic reviews and Meta-Analyses (PRISMA) checklist. MEDLINE (Ovid),
      EMBASE and Cochrane were systematically searched, as well as grey literature, to
      identify articles which defined the term polypharmacy (without any limits on the
      types of definitions) and were in English, published between 1st January 2000 and
      30th May 2016. Definitions were categorised as i. numerical only (using the
      number of medications to define polypharmacy), ii. numerical with an associated
      duration of therapy or healthcare setting (such as during hospital stay) or iii.
      Descriptive (using a brief description to define polypharmacy). RESULTS: A total
      of 1156 articles were identified and 110 articles met the inclusion criteria.
      Articles not only defined polypharmacy but associated terms such as minor and
      major polypharmacy. As a result, a total of 138 definitions of polypharmacy and
      associated terms were obtained. There were 111 numerical only definitions (80.4%
      of all definitions), 15 numerical definitions which incorporated a duration of
      therapy or healthcare setting (10.9%) and 12 descriptive definitions (8.7%). The
      most commonly reported definition of polypharmacy was the numerical definition of
      five or more medications daily (n = 51, 46.4% of articles), with definitions
      ranging from two or more to 11 or more medicines. Only 6.4% of articles
      classified the distinction between appropriate and inappropriate polypharmacy,
      using descriptive definitions to make this distinction. CONCLUSIONS: Polypharmacy
      definitions were variable. Numerical definitions of polypharmacy did not account
      for specific comorbidities present and make it difficult to assess safety and
      appropriateness of therapy in the clinical setting.

PMID- 29017449
TI  - Circulating adipocyte fatty acid-binding protein is a predictor of cardiovascular
      events in patients with stable angina undergoing percutaneous coronary
      intervention.
AB  - BACKGROUND: Adipocyte fatty acid-binding protein (A-FABP) is expressed in both
      adipocytes and macrophages. Recent studies have shown that A-FABP is secreted by
      adipocytes and that the A-FABP concentration is associated with obesity, insulin
      resistance, and atherosclerosis. We have reported that the coronary
      atherosclerotic burden is associated with the serum A-FABP concentration. In the
      present study, we investigated whether the serum A-FABP concentration is
      associated with prognosis in patients with stable angina pectoris who have
      undergone percutaneous coronary intervention (PCI). METHODS: This was a
      prospective single-center trial. In total, 130 patients with stable angina
      pectoris undergoing their first PCI were enrolled from August 2008 to July 2010
      at Kagawa Prefectural Central Hospital. The primary endpoints were cardiovascular
      death, nonfatal myocardial infarction, nonfatal stroke, revascularization, and
      hospitalization for heart failure. RESULTS: During the follow-up (median, 50
      months; interquartile range, 23-66 months), 49 cardiovascular events occurred.
      Kaplan-Meier analysis showed that the cumulative incidence of the primary
      endpoints in the high A-FABP group (median A-FABP concentration of >= 18.6 ng/ml)
      was greater than that in the low A-FABP group. Cox analysis showed that the A
      FABP concentration was an independent predictor of cardiovascular events adjusted
      for age and the presence of multi-vessel disease (hazard ratio, 1.03; 95%
      confidence interval, 1.01-1.04; p = 0.01). CONCLUSION: The serum A-FABP
      concentration is associated with prognosis in patients with stable angina
      undergoing PCI, suggesting that the serum A-FABP concentration could be useful
      for risk assessment of secondary prevention. TRIAL REGISTRATION: UMIN Clinical
      Trials Registry UMIN000029283 (registration date: September 25, 2017),
      retrospectively registered.

PMID- 29017450
TI  - Complete genome sequence of Citrobacter werkmanii strain BF-6 isolated from
      industrial putrefaction.
AB  - BACKGROUND: In our previous study, Citrobacter werkmanii BF-6 was isolated from
      an industrial spoilage sample and demonstrated an excellent ability to form
      biofilms, which could be affected by various environmental factors. However, the
      genome sequence of this organism has not been reported so far. RESULTS: We report
      the complete genome sequence of C. werkmanii BF-6 together with the description
      of the genome features and its annotation. The size of the complete chromosome is
      4,929,789 bp with an average coverage of 137*. The chromosome exhibits an average
      G + C content of 52.0%, and encodes 4570 protein coding genes, 84 tRNA genes, 25
      rRNA operons, 3 microsatellite sequences and 34 minisatellite sequences. A
      previously unknown circular plasmid designated as pCW001 was also found with a
      length of 212,549 bp and a G + C content of 48.2%. 73.5%, 75.6% and 92.6% of the
      protein coding genes could be assigned to GO Ontology, KEGG Pathway, and COG
      (Clusters of Orthologous Groups) categories respectively. C. werkmanii BF-6 and
      C. werkmanii NRBC 105721 exhibited the closest evolutionary relationships based
      on 16S ribosomal RNA and core-pan genome assay. Furthermore, C. werkmanii BF-6
      exhibits typical bacterial biofilm formation and development. In the RT-PCR
      experiments, we found that a great number of biofilm related genes, such as bsmA,
      bssR, bssS, hmsP, tabA, csgA, csgB, csgC, csgD, csgE, and csgG, were involved in
      C. werkmanii BF-6 biofilm formation. CONCLUSIONS: This is the first complete
      genome of C. werkmanii. Our work highlights the potential genetic mechanisms
      involved in biofilm formation and paves a way for further application of C.
      werkmanii in biofilms research.

PMID- 29017451
TI  - Multiplex PCR point of care testing versus routine, laboratory-based testing in
      the treatment of adults with respiratory tract infections: a quasi-randomised
      study assessing impact on length of stay and antimicrobial use.
AB  - BACKGROUND: Laboratory-based respiratory pathogen (RP) results are often
      available too late to influence clinical decisions such as hospitalisation or
      antibiotic treatment due to time delay in transport of specimens and testing
      schedules. Ward-based i.e. point of care (POC) testing providing rapid results
      may alter the clinical management pathway. METHODS: FilmArray(r) RP polymerase
      chain reaction (PCR) systems were placed in three in-patient and out-patient
      medical areas. Patients presenting with influenza-like illness /upper respiratory
      tract infection +/- lower RTI were recruited between January-July 2015.
      FilmArray(r) POC testing occurred on even days of the month (intervention) or
      routine, laboratory-based RP PCR testing +/- atypical serology on odd days
      (control). The primary outcome was length of hospital stay. The secondary
      outcomes were impact on the use of antimicrobials, readmissions, all-cause
      mortality, length of ward stay and turn-around time (TAT) (time to result from
      admission). RESULTS: Of 606 eligible patients, 545 (89.9%) were included; 211 in
      the control arm and 334 in the intervention arm. 20% of control arm patients and
      24% of intervention arm patients had an RP detected. POC testing was not
      associated with the primary outcome measure, length of stay, but reduced the TAT
      from 39.5 h to 19.0 h, p < 0.001. Only the prescribing decision differed between
      study arms, p < 0.001. When antivirals were given, the intervention was
      associated with a reduction in the median time to the first dose of 36 h and
      allowed appropriate treatment of mycoplasma infection. CONCLUSIONS: We found no
      association between respiratory PCR POC testing and length of stay or most of the
      secondary outcomes except the antimicrobial prescribing decision. This was
      probably due to a delay in initiating FilmArray(r) testing. Despite this, POC
      testing allowed time-critical antivirals to be given significantly faster,
      appropriate mycoplasma treatment and results were available considerably faster
      than routine, laboratory-based testing. Ward-staff of all grades performed POC
      testing without difficulty suggesting potential use across many divergent
      healthcare settings. Further studies evaluating the implementation of rapid
      respiratory PCR POC testing and the effect on length of stay and antimicrobial
      use are required. TRIAL REGISTRATION: ISRCTN10470967 , Retrospectively
      Registered, 30/6/2015.

PMID- 29017453
TI  - Positive and negative outcomes of informal caregiving at home and in
      institutionalised long-term care: a cross-sectional study.
AB  - BACKGROUND: Our ageing society is putting tremendous strain on public health and
      welfare programs to meet the needs of ageing individuals. Promoting informal
      caregiving is one way for policymakers to reduce this burden. However, caregiving
      may be experienced as stressful and is associated with adverse health
      consequences. While quite a lot of research focuses on caregiving for community
      dwelling older adults, little is known about informal care in institutionalised
      long-term care (ILTC). Therefore, the objectives of this study were: 1) to
      compare characteristics of informal caregivers and care receivers and caregiver
      outcomes - at home and in ILTC; 2) to study the association between these
      characteristics and positive and negative caregiver outcomes; 3) to investigate
      the moderating effect of the setting (at home vs. ILTC) on these associations.
      METHODS: A cross-sectional study was conducted using the TOPICS-MDS DataSet. A
      total of 5197 Dutch dyads were included. The average age of the care receivers
      and caregivers was respectively 80.7 years and 63.2 years. Several
      sociodemographic, health-related and caregiving-related characteristics of care
      receiver and caregiver and two caregiver outcomes (i.e., subjective burden and
      care-related quality of life) were included in the analyses. RESULTS: Caregivers
      in both settings experienced comparable levels of subjective burden. Caregivers
      at home had slightly lower care-related quality of life than caregivers in ILTC.
      Several care receiver characteristics (i.e., male sex, married/cohabiting, more
      morbidities/disability, and less self-perceived health/psychological wellbeing)
      and several caregiver characteristics (i.e., female sex, being younger, living
      together with the care receiver, more objective burden, less self-perceived
      health, and more support) were associated with an increase in burden and/or a
      decrease in care-related quality of life. Some of these associations were
      stronger for dyads at home compared to dyads in ILTC. CONCLUSIONS: Informal
      caregiving does not stop with admission to an ILTC facility. Both settings need
      an informal caregiving policy, which is (1) tailored to the individual
      characteristics of care receivers and caregivers; (2) pays attention to the
      identified risk groups; and (3) reduces the negative caregiver outcomes and
      emphasizes the positive outcomes at the same time.

PMID- 29017452
TI  - Whole genome sequencing for the molecular characterization of carbapenem
      resistant Klebsiella pneumoniae strains isolated at the Italian ASST
      Fatebenefratelli Sacco Hospital, 2012-2014.
AB  - BACKGROUND: The emergence of carbapenem-resistant Klebsiella pneumoniae strains
      is threatening antimicrobial treatment. METHODS: Sixty-eight carbapenemase
      producing K. pneumoniae strains isolated at Luigi Sacco University Hospital-ASST
      Fatebenefratelli Sacco (Milan, Italy) between 2012 and 2014 were characterised
      microbiologically and molecularly. They were tested for drug susceptibility and
      carbapenemase phenotypes, investigated by means of repetitive extra-genic
      palindromic polymerase chain reaction (REP-PCR), and fully sequenced by means of
      next-generation sequencing for the in silico analysis of multi-locus sequence
      typing (MLST), their resistome, virulome and plasmid content, and their core
      single nucleotide polymorphism (SNP) genotypes. RESULTS: All of the samples were
      resistant to carbapenems, other beta-lactams and ciprofloxacin; many were
      resistant to aminoglycosides and tigecycline; and seven were resistant to
      colistin. Resistome analysis revealed the presence of blaKPC genes and, less
      frequently blaSHV, blaTEM, blaCTX-M and blaOXA, which are related to resistance
      to carbapenem and other beta-lactams. Other genes conferring resistance to
      aminoglycoside, fluoroquinolone, phenicol, sulphonamide, tetracycline,
      trimethoprim and macrolide-lincosamide-streptogramin were also detected. Genes
      related to AcrAB-TolC efflux pump-dependent and pump-independent tigecycline
      resistance mechanisms were investigated, but it was not possible to clearly
      correlate the genomic features with tigecycline resistance because of the
      presence of a common mutation in susceptible, intermediate and resistant strains.
      Concerning colistin resistance, the mgrB gene was disrupted by an IS5-like
      element, and the mobile mcr-1 and mcr-2 genes were not detected in two cases. The
      virulome profile revealed type-3 fimbriae and iron uptake system genes, which are
      important during the colonisation stage in the mammalian host environment. The in
      silico detected plasmid replicons were classified as IncFIB(pQil), IncFIB(K),
      ColRNAI, IncX1, IncX3, IncFII(K), IncN, IncL/M(pMU407) and IncFIA(HI1). REP-PCR
      showed five major clusters, and MLST revealed six different sequence types: 512,
      258, 307, 1519, 745 and 101. Core SNP genotyping, which led to four clusters,
      correlated with the MLST data. Isolates of the same sequencing type often had
      common genetic traits, but the SNP analysis allowed greater strain tracking and
      discrimination than either the REP-PCR or MLST analysis. CONCLUSION: Our findings
      support the importance of implementing bacterial genomics in clinical medicine in
      order to complement traditional methods and overcome their limited resolution.

PMID- 29017454
TI  - Productivity losses and public finance burden attributable to breast cancer in
      Poland, 2010-2014.
AB  - BACKGROUND: Apart from the health and social burden of the disease, breast cancer
      (BC) has important economic implications for the sick, health system and whole
      economy. There has been a growing interest in the economic aspects of breast
      cancer and analyses of the disease costs seem to be the most explored topic.
      However, the results from these studies are hardly comparable. With this study we
      aim to contribute to the field by providing estimates of productivity losses and
      public finance burden attributable to BC in Poland. METHODS: We used
      retrospective prevalence-based top-down approach to estimate the productivity
      losses (indirect costs) of BC in Poland in the period 2010-2014. Human capital
      method (HCM) and societal perspective were used to estimate the costs of:
      absenteeism of the sick and caregivers, presenteeism of the sick and caregivers,
      disability, and premature mortality. We also used figures illustrating public
      finance burden attributable to the disease. Deterministic sensitivity analysis
      was performed to assess the stability of the estimates. A variety of data sources
      were used with the social insurance system and Polish National Cancer Registry
      being the most important ones. RESULTS: Productivity losses associated with BC in
      Poland were ?583.7 million in 2010 and they increased to ?699.7 million in 2014.
      Throughout the period these costs accounted for 0.162-0.171% of GDP, an
      equivalent of 62,531-65,816 per capita GDP. Losses attributable to disability and
      premature mortality proved to be the major cost drivers with 27.6%-30.6% and
      22.0%-24.6% of the total costs respectively. The costs due to caregivers'
      presenteeism were negligible (0.1% of total costs). Public finance expenditure
      for social insurance benefits to BC sufferers ranged from ?50.2 million (2010) to
      ?56.6 million (2014), an equivalent of 0.72-0.79% of expenditures for all
      diseases. Potential losses in public finance revenues accounted for ?173.9
      million in 2010 and ?211.0 million in 2014. Sensitivity analysis showed that the
      results were robust to changes in the model parameters. CONCLUSIONS: The
      productivity losses attributable to BC in Poland were a sizable burden for the
      society. They contributed both to decreased economy output and to public finance
      deficit.

PMID- 29017455
TI  - The EC90 of remifentanil for blunting cardiovascular responses to head fixation
      for neurosurgery under total intravenous anesthesia with propofol and
      remifentanil based on bispectral index monitoring: estimation with the biased
      coin up-and-down sequential method.
AB  - BACKGROUND: Head fixation can induce hemodynamic instability. Remifentanil is
      commonly used with propofol for total intravenous anesthesia (TIVA) during
      neurosurgery. This study investigated the 90% effective concentration (EC90) of
      remifentanil for blunting of cardiovascular responses to head fixation during
      neurosurgery via bispectral index (BIS) monitoring. METHODS: Fifty patients
      undergoing neurosurgery requiring head fixation were enrolled. This study was
      performed using the biased coin up-and-down design sequential method (BCD). After
      tracheal intubation, the effect-site target concentration (Ce) of remifentanil
      was adjusted to achieve hemodynamic stability and reset to the level
      preoperatively assigned to each patient, according to the BCD method,
      approximately 10 min before head fixation. Baseline hemodynamic values were
      recorded before head fixation. An ineffective response was defined as a case with
      a > 20% increase in hemodynamic values from baseline. Otherwise, the response was
      determined to be effective. The EC90 of remifentanil was calculated as a modified
      isotonic estimator. RESULTS: Forty-three patients completed this study. The EC90
      of remifentanil for blunting cardiovascular responses to head fixation was
      estimated to be 6.48 ng/mL (95% CI, 5.94-6.83 ng/mL). CONCLUSIONS: Adjustment of
      the Ce of remifentanil to approximately 6.5 ng/mL before head fixation could
      prevent noxious cardiovascular responses in 90% of neurosurgical ASA I-II
      patients aged 20 to 65 years old during propofol target-controlled infusion
      titrated to maintain BIS between 40 and 50. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier NCT01489137 , retrospectively registered 5 December
      2011.

PMID- 29017456
TI  - Prevalence and risk factors of hepatitis B infection among mothers and children
      with hepatitis B infected mother in upper Dolpa, Nepal.
AB  - BACKGROUND: Hepatitis B Virus (HBV) infection is a worldwide public health
      problem. In Nepal, the prevalence of HBV is found to be low (0.9%), although high
      prevalence (>=8%) of HBV infection is depicted among subgroup/population in the
      mountain region by various studies. This study assessed the prevalence and the
      risk of HBV infection among mothers, as well as among the youngest child under 5
      years old living with hepatitis B positive mothers in Dolpa, the most remote
      mountain district of Nepal. METHODS: The cross sectional study survey was
      conducted between June and July 2014. All mothers with their youngest child under
      5 years old were invited to participate in the survey and tested for hepatitis B
      surface antigen (HBsAg). The HBsAg positive mothers were further tested by 5
      panel HBV test card. Children living with HBsAg positive mothers were also tested
      for HBsAg. RESULTS: One hundred fifty-one mothers, comprising 37% of the total
      study population in the selected Village Development Committees (VDCs), were
      surveyed in the mobile health camps. The seroprevalence of HBsAg among mothers
      and their youngest child under 5 years old living with HBsAg positive mothers
      were 17% (95% CI, 11.01-22.99%) and 48% (95%CI, 28.42-67.58%) respectively. The
      majority of HBV infected mothers were indigenous (84%) followed by Dalit (4%) and
      other castes (12%). Among HBV infected mothers, 40% were hepatitis B envelope
      antigen (HBeAg) positive. The prevalence of HBsAg was higher among children
      living with HBeAg positive mothers as compared to HBeAg negative (60% vs 40%) and
      male children compared to female (60% vs 33%). Thirty-six percent of children
      were vaccinated with a full course of the hepatitis B vaccine. Of these
      vaccinated children, 56% were HBsAg sero-positive. CONCLUSIONS: The HBV infection
      rate is high among mothers and children living with HBsAg positive mothers in the
      indigenous population of the most remote mountain community of Nepal.

PMID- 29017457
TI  - Evaluation of a pulsed xenon ultraviolet disinfection system to decrease
      bacterial contamination in operating rooms.
AB  - BACKGROUND: Environmental cleanliness is one of the contributing factors for
      surgical site infections in the operating rooms (ORs). To decrease environmental
      contamination, pulsed xenon ultraviolet (PX-UV), an easy and safe no-touch
      disinfection system, is employed in several hospital environments. The positive
      effect of this technology on environmental decontamination has been observed in
      patient rooms and ORs during the end-of-day cleaning but so far, no study
      explored its feasibility between surgical cases in the OR. METHODS: In this
      study, 5 high-touch surfaces in 30 ORs were sampled after manual cleaning and
      after PX-UV intervention mimicking between-case cleaning to avoid the disruption
      of the ORs' normal flow. The efficacy of a 1-min, 2-min, and 8-min cycle were
      tested by measuring the surfaces' contaminants by quantitative cultures using
      Tryptic Soy Agar contact plates. RESULTS: We showed that combining standard
      between-case manual cleaning of surfaces with a 2-min cycle of disinfection using
      a portable xenon pulsed ultraviolet light germicidal device eliminated at least
      70% more bacterial load after manual cleaning. CONCLUSIONS: This study showed the
      proof of efficacy of a 2-min cycle of PX-UV in ORs in eliminating bacterial
      contaminants. This method will allow a short time for room turnover and a
      potential reduction of pathogen transmission to patients and possibly surgical
      site infections.

PMID- 29017459
TI  - An attention-based effective neural model for drug-drug interactions extraction.
AB  - BACKGROUND: Drug-drug interactions (DDIs) often bring unexpected side effects.
      The clinical recognition of DDIs is a crucial issue for both patient safety and
      healthcare cost control. However, although text-mining-based systems explore
      various methods to classify DDIs, the classification performance with regard to
      DDIs in long and complex sentences is still unsatisfactory. METHODS: In this
      study, we propose an effective model that classifies DDIs from the literature by
      combining an attention mechanism and a recurrent neural network with long short
      term memory (LSTM) units. In our approach, first, a candidate-drug-oriented input
      attention acting on word-embedding vectors automatically learns which words are
      more influential for a given drug pair. Next, the inputs merging the position-
      and POS-embedding vectors are passed to a bidirectional LSTM layer whose outputs
      at the last time step represent the high-level semantic information of the whole
      sentence. Finally, a softmax layer performs DDI classification. RESULTS:
      Experimental results from the DDIExtraction 2013 corpus show that our system
      performs the best with respect to detection and classification (84.0% and 77.3%,
      respectively) compared with other state-of-the-art methods. In particular, for
      the Medline-2013 dataset with long and complex sentences, our F-score far exceeds
      those of top-ranking systems by 12.6%. CONCLUSIONS: Our approach effectively
      improves the performance of DDI classification tasks. Experimental analysis
      demonstrates that our model performs better with respect to recognizing not only
      close-range but also long-range patterns among words, especially for long,
      complex and compound sentences.

PMID- 29017458
TI  - Lifestyle, gene gain and loss, and transcriptional remodeling cause divergence in
      the transcriptomes of Phytophthora infestans and Pythium ultimum during potato
      tuber colonization.
AB  - BACKGROUND: How pathogen genomes evolve to support distinct lifestyles is not
      well-understood. The oomycete Phytophthora infestans, the potato blight agent, is
      a largely biotrophic pathogen that feeds from living host cells, which become
      necrotic only late in infection. The related oomycete Pythium ultimum grows
      saprophytically in soil and as a necrotroph in plants, causing massive tissue
      destruction. To learn what distinguishes their lifestyles, we compared their gene
      contents and expression patterns in media and a shared host, potato tuber.
      RESULTS: Genes related to pathogenesis varied in temporal expression pattern,
      mRNA level, and family size between the species. A family's aggregate expression
      during infection was not proportional to size due to transcriptional remodeling
      and pseudogenization. Ph. infestans had more stage-specific genes, while Py.
      ultimum tended towards more constitutive expression. Ph. infestans expressed more
      genes encoding secreted cell wall-degrading enzymes, but other categories such as
      secreted proteases and ABC transporters had higher transcript levels in Py.
      ultimum. Species-specific genes were identified including new Pythium genes,
      perforins, which may disrupt plant membranes. Genome-wide ortholog analyses
      identified substantial diversified expression, which correlated with sequence
      divergence. Pseudogenization was associated with gene family expansion,
      especially in gene clusters. CONCLUSION: This first large-scale analysis of
      transcriptional divergence within oomycetes revealed major shifts in genome
      composition and expression, including subfunctionalization within gene families.
      Biotrophy and necrotrophy seem determined by species-specific genes and the
      varied expression of shared pathogenicity factors, which may be useful targets
      for crop protection.

PMID- 29017460
TI  - 27-gauge and 25-gauge vitrectomy day surgery for idiopathic epiretinal membrane.
AB  - BACKGROUND: This study compared the postoperative outcomes of 27-gauge (G) and 25
      G vitrectomy performed for the treatment of idiopathic epiretinal membrane (ERM).
      METHODS: The study design was single center, retrospective, interventional case
      series. Two hundred consecutive eyes that underwent primary vitrectomy for ERM
      (27-G vitrectomy in 100 eyes and 25-G vitrectomy in 100 eyes) were studied for 6
      months. In all eyes, scleral tunnels were made using angle incisions, and air or
      gas exchange was performed. RESULTS: There were no significant differences in
      age, spherical diopter power, as well as preoperative Early Treatment Diabetic
      Retinopathy Study (ETDRS) score, central retinal thickness (CRT), and intraocular
      pressure between the 27-G and 25-G groups. The proportions of simultaneous
      cataract surgery (27-G vs. 25-G: 82% vs. 90%), air-filled eyes (99% vs. 98%), and
      scleral wound suture at the end of surgery (0% vs. 0%) were not significantly
      different between two groups. The mean operation time for vitrectomy was
      significantly (P = 0.0322) longer by 4 min for 27-G (37 min) compared to 25-G (33
      min) vitrectomy. Gain in ETDRS score was significantly (P = 0.0421) better in 27
      G group (4.7 +/- 8.1 letters) compared to 25-G group (1.1 +/- 13.6 letters) at 1
      month post-vitrectomy, but not significantly different at 3 and 6 months (P =
      0.0835 and 0.0569, respectively). Decrease in CRT was significantly (P = 0.0354)
      greater in 27-G group (-24.2 +/- 50.0 MUm) compared to 25-G group (-8.0 +/- 48.6
      MUm) at 1 month post-vitrectomy, but not significantly different at 3 and 6
      months (P = 0.6059 and 0.1725, respectively). On postoperative day 1, hypotony
      (<= 6 mmHg) was observed in 2 eyes in 27-G group and 6 eyes in 25-G group, while
      ocular hypertension (>= 25 mmHg) was found in 4 eyes in 27-G group and 11 eyes in
      25-G group, with no significant differences between two groups. Postoperative
      complications requiring treatment occurred in one eye (vitreous hemorrhage) in 27
      G group, and in two eyes (vitreous hemorrhage and retinal detachment in one eye
      each) in 25-G group. CONCLUSIONS: Although 27-G vitrectomy requires operation
      time of 4 min longer compared to 25-G vitrectomy for ERM surgery, using the 27-G
      system results in earlier recovery of visual acuity, CRT improvement and
      stabilized ocular pressure.

PMID- 29017461
TI  - Feasibility and safety of early discharge after transfemoral transcatheter aortic
      valve implantation - rationale and design of the FAST-TAVI registry.
AB  - BACKGROUND: There is an increasing trend towards shorter hospital stays after
      transcatheter aortic valve implantation (TAVI), in particular for patients
      undergoing the procedure via transfemoral (TF) access. Preliminary data suggest
      that there exists a population of patients that can be discharged safely very
      early after TF-TAVI. However, current evidence is limited to few retrospective
      studies, encompassing relatively small sample sizes. METHODS: The Feasibility And
      Safety of early discharge after Transfemoral TAVI (FAST-TAVI) registry is a
      prospective observational registry that will be conducted at 10 sites across
      Italy, the Netherlands and the UK. Patients will be included if they have been
      scheduled to undergo TF-TAVI with the balloon-expandable SAPIEN 3 transcatheter
      heart valve (THV; Edwards Lifesciences, Irvine, CA). The primary endpoint is a
      composite of all-cause mortality, vascular-access-related complications,
      permanent pacemaker implantation, stroke, re-hospitalisation due to cardiac
      reasons, kidney failure and major bleeding, occurring during the first 30 days
      after hospital discharge. Patients will be stratified according to whether they
      were high or low risk for early discharge (<=3 days) (following pre-specified
      criteria), and according to whether or not they were discharged early. Secondary
      endpoints will include time-to-event (Kaplan-Meier) analysis for the primary
      outcome and its individual components, analysis of the relative costs of early
      and late discharge, and changes in short- and long-term quality of life.
      Multivariate logistic regression will be used to identify factors that indicate
      that a patient may be suitable for early discharge. DISCUSSION: The data gathered
      in the FAST-TAVI registry should help to clarify the safety of early discharge
      after TF-TAVI and to identify patient and procedural characteristics that make
      early discharge from hospital a safe and cost-effective strategy. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT02404467 (registration first
      received March 23rd 2015).

PMID- 29017462
TI  - Vitamin D deficiency was common among nursing home residents and associated with
      dementia: a cross sectional study of 545 Swedish nursing home residents.
AB  - BACKGROUND: Residents of nursing homes may have low 25-hydroxyvitamin D (25OHD)
      concentrations. Associations between vitamin D and cognitive performance,
      dementia and susceptibility to infections are not clearly established. The aim of
      this study was to investigate the prevalence of vitamin D deficiency and to
      identify associated factors among residents of nursing homes for elderly.
      METHODS: In this cross-sectional study blood samples for analysis of 25OHD were
      collected from all participating residents of Swedish nursing homes for the
      elderly from January to March 2012. EXCLUSION CRITERIA: dementia too severe to
      collect a blood test, terminally ill or refusing participation. OUTCOME MEASURES:
      Serum 25OHD concentrations. Logistic regression to evaluate factors associated
      with vitamin D deficiency (25OHD < 25 nmol/L). RESULTS: Blood samples were
      obtained from 545 of 901 residents of 22 nursing homes. Mean age 86 years (SD
      6.9), 68% were women. Prevalence of vitamin D supplementation 17%, dementia 55%,
      lack of appetite >=3 months 45% and any antibiotic treatment during the last 6
      months 30%. Serum 25OHD concentrations: mean 34 nmol/L (SD 21, median 27, range 4
      125), 82% (448/545) had 25OHD < 50 nmol/L and 41% (224/545) had 25OHD < 25
      nmol/L. Adjusted OR (95% CI; p-value) for possible predictors of vitamin D
      deficiency (25OHD < 25 nmol/L): vitamin D supplementation 0.075 (0.031-0.18; p <
      0.001), lack of appetite >=3 months 0.75 (0.50-1.1; p = 0.15), hours
      outdoors/week 0.99 (0.96-1.0; p = 0.62), Fitzpatrick skin phototype (4-6) 0.69
      (0.44-1.1; p = 0.12); dementia 2.3 (1.5-3.4; p < 0.001) and antibiotics last 6
      months 1.6 (1.1-2.6; p < 0.029), adjusted for age and gender. CONCLUSIONS:
      Vitamin D deficiency was common among nursing home residents and strongly
      associated with dementia. Regardless of causality or not, it is important to be
      alert for vitamin D deficiency in nursing homes residents with dementia. As
      expected vitamin D supplementation was associated with less vitamin D deficiency,
      however lack of appetite, staying outdoors and skin phototype were not
      significant predictors. Antibiotic treatments during the last 6 months were
      associated with vitamin D deficiency, potentially supporting the hypothesis that
      vitamin D deficiency is associated with infections.

PMID- 29017463
TI  - Subjective health expectations of patients with age-related macular degeneration
      treated with antiVEGF drugs.
AB  - BACKGROUND: Subjective expectations regarding future health may influence
      patients' judgement of current health and treatment effects, as well as adherence
      to therapies in chronic diseases. We aimed to explore subjective expectations on
      longevity and future health-related quality of life (HRQOL) of patients with age
      related macular degeneration (AMD) treated with antiVEGF injections and analyse
      the influencing factors. METHODS: Consecutive AMD patients in two ophthalmology
      centres were included. Demographics, clinical characteristics and informal care
      utilisation were recorded. Current health was evaluated by the EQ-5D generic
      health status questionnaire and time trade-off (TTO) methods. Happiness was
      measured on a visual analogue scale (VAS). Subjective life-expectancy and
      expected EQ-5D status at ages 70, 80 and 90 were surveyed. T-test was applied to
      compare subgroups and Pearson correlations were performed to analyse
      relationships between variables. RESULTS: One hundred twenty two patients were
      involved (females 62%) with a mean (SD) age of 75.2 (7.9) years and disease
      duration of 2.9 (2.5) years. The majority were in AREDS-4 state, the better eye's
      ETDRS was 64.7 (15.4). EQ-5D and TTO revealed moderate deterioration of health
      (0.66 vs. 0.72, p = 0.131), happiness VAS was 6.3 (2.2). Correlation between EQ
      5D and ETDRS was moderate (R = 0.242, p < 0.05) and having both versus one eye in
      AREDS-4 resulted lower TTO (0.68 vs. 0.83; p = 0.013). Subjective life-expectancy
      did not differ significantly from statistical life-expectancy and had no
      significant impact on TTO. The self-estimated mean EQ-5D score was 0.60, 0.40 and
      0.24 for ages 70, 80 and 90 which is lower than the population norm of age-groups
      65-74, 75-84 and 85+ (0.77, 0.63 and 0.63, respectively). Age, gender, current EQ
      5D, need for informal care and happiness were deterministic factors of subjective
      health expectations. CONCLUSION: AMD patients with antiVEGF treatment have
      comparable HRQOL as the age-matched general public but expect a more severe
      deterioration of health with age. Older patients with worse HRQOL have worse
      subjective expectations. Exploring patients' health expectations provides an
      opportunity for ophthalmologists to correct misperceptions and improve the
      quality of AMD care. Further studies should provide evidences on the relationship
      between subjective expectations and actual health outcomes, and on its impact on
      patients' AMD-specific health behaviour.

PMID- 29017466
TI  - Prevalence of antimicrobial resistant Escherichia coli from patients with
      suspected urinary tract infection in primary care, Denmark.
AB  - BACKGROUND: Escherichia coli is the most common pathogen causing Urinary Tract
      Infections (UTI). Data from the current National Surveillance program in Denmark
      (DANMAP) may not accurately represent the prevalence of resistant E. coli in
      primary care, because only urine samples from complicated cases may be forwarded
      to the microbiological departments at hospitals for diagnostic examination. The
      aim of this study was to assess the prevalence of resistant E. coli to the most
      commonly used antimicrobial agents in primary care in a consecutive sample of
      patients from general practice. METHODS: Observational study carried out from
      December 2014 to December 2015. Thirty-nine general practices from The Capital
      Region of Denmark included adult patients with urinary tract symptoms and
      suspected UTI. All urine samples were sent to the central laboratory Statens
      Serum Institut (SSI). Significant bacteriuria was interpreted according to the
      European Urinalysis Standards. Susceptibility testing was performed and
      interpreted according to the European Committee on Antimicrobial Susceptibility
      Testing (EUCAST) standards. RESULTS: From the 39 general practices 505 patients
      were recruited. Completed data were obtained from 485 (96%) patients. According
      to the European Urinalysis Standards, 261 (54%) patients had positive
      bacteriuria. The most common uropathogen in patients with uncomplicated (uUTI)
      and complicated (cUTI) urinary tract infection was E. coli 105 (69%) and 76
      (70%), respectively. Eighty-two (45%) of 181 E. coli isolates were resistant to
      at least one of the tested antibiotics and 50 out of 82 isolates were resistant
      to two or more antimicrobial agents. The highest resistance-rate was found
      against ampicillin 34% (95% CI 24;42) in uUTI and 36% (24;46) in cUTI. There were
      no differences in the distribution of resistance between uncomplicated and
      complicated cases. The prevalence of resistance was similar to the one reported
      in DANMAP 2014. CONCLUSION: In E. coli from uUTI there is high resistance rates
      to antimicrobial agents commonly used in primary care. There was no difference in
      the distribution of resistant E. coli in suspected uUTI vs cUTI. In Denmark, data
      from the National Surveillance program DANMAP can guide the decision for choice
      of antibiotic in patients with suspected UTI seeking care in primary care. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02249273 .

PMID- 29017464
TI  - Respective contribution of the cephalic neural crest and mesoderm to SIX1
      expressing head territories in the avian embryo.
AB  - BACKGROUND: Vertebrate head development depends on a series of interactions
      between many cell populations of distinct embryological origins. Cranial
      mesenchymal tissues have a dual embryonic source: - the neural crest (NC), which
      generates most of craniofacial skeleton, dermis, pericytes, fat cells, and
      tenocytes; and - the mesoderm, which yields muscles, blood vessel endothelia and
      some posterior cranial bones. The molecular players that orchestrate co
      development of cephalic NC and mesodermal cells to properly construct the head of
      vertebrates remain poorly understood. In this regard, Six1 gene, a vertebrate
      homolog of Drosophila Sine Oculis, is known to be required for development of
      ear, nose, tongue and cranial skeleton. However, the embryonic origin and fate of
      Six1-expressing cells have remained unclear. In this work, we addressed these
      issues in the avian embryo model by using quail-chick chimeras, cephalic NC
      cultures and immunostaining for SIX1. RESULTS: Our data show that, at early NC
      migration stages, SIX1 is expressed by mesodermal cells but excluded from the NC
      cells (NCC). Then, SIX1 becomes widely expressed in NCC that colonize the pre
      otic mesenchyme. In contrast, in the branchial arches (BAs), SIX1 is present only
      in mesodermal cells that give rise to jaw muscles. At later developmental stages,
      the distribution of SIX1-expressing cells in mesoderm-derived tissues is
      consistent with a possible role of this factor in the myogenic program of all
      types of head muscles, including pharyngeal, extraocular and tongue muscles. In
      NC derivatives, SIX1 is notably expressed in perichondrium and chondrocytes of
      the nasal septum and in the sclera, although other facial cartilages such as
      Meckel's were negative at the stages considered. Moreover, in cephalic NC
      cultures, chondrocytes and myofibroblasts, not the neural and melanocytic cells
      express SIX1. CONCLUSION: The present results point to a dynamic tissue-specific
      expression of SIX1 in a variety of cephalic NC- and mesoderm-derived cell types
      and tissues, opening the way for further analysis of Six1 function in the
      coordinated development of these two cellular populations during vertebrate head
      formation.

PMID- 29017465
TI  - Frequency of arrhythmia symptoms and acceptability of implantable cardiac
      monitors in Hemodialysis patients.
AB  - BACKGROUND: Arrhythmia-related complications and sudden death are common in
      dialysis patients. However, routine cardiac monitoring has so far not been
      feasible. Miniaturization of implantable cardiac monitors offers a new paradigm
      for detection and management of arrhythmias in dialysis patients. The goal of our
      study was to determine the frequency of arrhythmia-related symptoms in
      hemodialysis patients and to assess their willingness to undergo implantation of
      a cardiac monitor. METHODS: We conducted a survey of in-center hemodialysis
      patients at a hemodialysis clinic in Baltimore, Maryland. We assessed the
      frequency of arrhythmia-related symptoms and willingness to undergo placement of
      an implantable cardiac monitor (LINQ, Medtronic Inc.). RESULTS: Forty six
      patients completed the survey. The mean age of the survey respondents was 59
      years and 65% were male. Symptoms were common with 74% (n = 34) of participants
      reporting at least one arrhythmia-related symptom and many [22% (n = 10)] had all
      3 symptoms. Among the patients with symptoms, 57% (n = 26) reported "heart
      skipping beats, flopping in chest or beating very hard," 61% (n = 28) reported
      "heart racing (palpitations)," and 37% (n = 17) reported feeling that they
      "passed out or almost passed out." The majority of the patients felt that the
      timing of the symptoms was unrelated to dialysis treatments. The acceptability of
      the monitoring device implantation was high, with 59% (n = 20) of patients with
      symptoms and 50% (n = 6) of patients without symptoms willing to consider it. The
      main reason for not considering the device was not wanting to have an implanted
      device. CONCLUSION: The prevalence of arrhythmia-related symptoms is high in
      hemodialysis patients and the majority would consider an implantable cardiac
      monitor if recommended by their physicians. Routine implantation of cardiac
      monitoring devices to manage arrhythmias in dialysis patients may be feasible and
      will provide further insights on the leading causes of morbidity and mortality in
      dialysis patients.

PMID- 29017468
TI  - Case report: the first case of human infection by adult of SPIROMETRA
      ERINACEIEUROPAEI in VIETNAM.
AB  - BACKGROUND: Tapeworms of the genus Spirometra include species whose larval stages
      can infect humans, causing a disease called sparganosis. Cases of human infection
      with adult worms are very rare and have been reported in Korea and China. Here we
      report the first case of human infection with an adult of Spirometra
      erinaceieuropaei in Vietnam. CASE PRESENTATION: A 23-year-old male was admitted
      to 103 Military Hospital, Hanoi, Vietnam with fever, weight loss and epigastric
      discomfort. Preliminary diagnosis based on discovery of parasite eggs in his
      faeces incorrectly determined a fluke as the agent of the infection and
      praziquantel was prescribed. Two days later he passed out proglottids in his
      stool. The tapeworm was identified as Spirometra erinaceieuropaei using
      morphological and molecular tools. CONCLUSION: This is the first case of human
      infection with adult worm of Spirometra erinaceieuropaei in Vietnam.

PMID- 29017467
TI  - Association between very advanced maternal age and adverse pregnancy outcomes: a
      cross sectional Japanese study.
AB  - BACKGROUND: While several studies have demonstrated the increased risk of
      pregnancy complications for women of advanced age, few studies have focused on
      women with very advanced age (>= 45), despite the increasing rate of pregnancy
      among such women. Furthermore, how such risks of increase in age differ by
      maternal characteristics are also poorly understood. Thus, we aimed to clarify
      pregnant outcomes among women with very advanced age and how the effect of age
      differs by method of conception and parity. METHODS: We used the national
      multicenter Japan Society of Obstetrics and Gynecology perinatal database,
      including 365,417 women aged 30 years or older who delivered a singleton between
      2005 and 2011. We divided women into four groups based on age (years): 30-34, 35
      39, 40-44, and >=45, and compared risk of adverse birth outcomes between the
      groups using Poisson regression. Effect modification by parity and use of
      assisted reproductive technology (ART) was also evaluated. RESULTS: Compared with
      women aged 30-34 years, women aged 45 or older had higher risk of emergency
      cesarean delivery [adjusted risk ratio (aRR): 1.77, 95% confidence interval (95%
      CI): 1.58-1.99], preeclampsia (aRR: 1.86, 95% CI: 1.43-2.42), severe preeclampsia
      (aRR: 2.03, 95% CI: 1.31-3.13), placenta previa (aRR: 2.17, 95% CI: 1.60-2.95),
      and preterm birth (aRR: 1.20, 95% CI: 1.04-1.39). The effect of older age on risk
      of emergency cesarean section, preeclampsia, and preterm birth were significantly
      greater among those who conceived naturally compared to those who conceived by
      ART. The effect on emergency cesarean section was stronger among primiparous
      women, whereas the risk of preeclampsia associated with older age was
      significantly greater among multiparous women. CONCLUSIONS: Very advanced
      maternal age (>= 45) was related to greater risk for adverse birth outcomes
      compared to younger women, especially for maternal complications including
      cesarean section, preeclampsia, severe preeclampsia, and placenta previa. The
      magnitude of the influence of age also differed by conception method and by
      parity.

PMID- 29017469
TI  - Relationship between interpersonal sensitivity and leukocyte telomere length.
AB  - BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of
      chromosomes, and telomere length represents a biological marker for cellular
      aging. Interpersonal sensitivity, excessive sensitivity to the behavior and
      feelings of others, is one of the vulnerable factors to depression. In the
      present study, we examined the effect of interpersonal sensitivity on telomere
      length in healthy subjects. METHODS: The subjects were 159 unrelated healthy
      Japanese volunteers. Mean age +/- SD (range) of the subjects was 42.3 +/- 7.8 (30
      61) years. Interpersonal sensitivity was assessed by the Japanese version of the
      Interpersonal Sensitivity Measure (IPSM). Leukocyte telomere length was
      determined by a quantitative real-time PCR method. RESULTS: Higher scores of the
      total IPSM were significantly (beta = -0.163, p = 0.038) related to shorter
      telomere length. In the sub-scale analysis, higher scores of timidity were
      significantly (beta = -0.220, p = 0.044) associated with shorter telomere length.
      CONCLUSIONS: The present study suggests that subjects with higher interpersonal
      sensitivity have shorter leukocyte telomere length, implying that interpersonal
      sensitivity has an impact on cellular aging.

PMID- 29017470
TI  - Soil transmitted Helminthiasis and associated risk factors among elementary
      school children in ambo town, western Ethiopia.
AB  - BACKGROUND: Soil-transmitted helminths (STHs) are widespread in underdeveloped
      countries. In Ethiopia, the prevalence and distribution of helminth infection
      varies by different exposing risk factors. We therefore investigated the
      prevalence of and risk factors of STHs infection in school children living in
      Ambo town, west Shoa Ethiopia. METHODS: In 2014/15, among 375 school children
      planed to be included in this study, only 321 school children were recruited in
      the study. Data onto school children from different schools were collected,
      including stool samples for qualitative STHs analysis. Questionnaire data on
      various demographic, housing and lifestyle variables were also available.
      RESULTS: Prevalence of any STHs infection was 12.6%. The respective prevalence of
      major soil-transmitted helminths is Ascaris (7.8%), Hookworm (2.8%) and Trichuris
      (2.2%). This study result shows STHs prevalence varies regards to age, sex,
      latrine use, family size and nail trimming. CONCLUSION: The results of the
      present study indicated that the percentage of positive finding for STHs in Ambo
      area is low. Besides, Large Family size, not nail trimming and unavailability of
      improved latrine were identified as predisposing factor for STHs infections. All
      school children enrolled and not enrolled in this study should be treated twice a
      year until the prevalence falls below the level of public health importance.

PMID- 29017471
TI  - Self-admission to inpatient treatment in psychiatry: lessons on implementation.
AB  - BACKGROUND: Interest has increased in programs offering self-admission to
      inpatient treatment for patients with severe psychiatric illness, whereby
      patients who are well-known to a service are afforded the opportunity to admit
      themselves at will for a brief period of time. The aim of the present study was
      to examine patient experiences of practical considerations during the start-up
      phase of a self-admission program in an eating disorder service. METHODS: Sixteen
      adult participants in a self-admission program at a specialist eating disorders
      service were interviewed at 6 months about their experiences during the
      implementation phase. A qualitative content analysis approach was applied in
      order to identify recurring themes. RESULTS: Six subcategories regarding
      implementation and logistics of self-admission were identified: "Start-up
      problems", "Problems associated with reserving a bed", "Lack of staff
      continuity", "Not enough emphasis on long-term goals", "Too demanding in terms of
      freedom and responsibility", and "Suggestions for alternative models".
      CONCLUSIONS: Practical recommendations can be offered for the implementation of
      future self-admission programs, such as thoroughly informing all participants
      about the rationale behind self-admission with particular emphasis on patient
      accountability, establishing a waiting list procedure for occasions when all
      designated beds are occupied, and assigning an individual contact staff member
      responsible for each self-admitted patient. TRIAL REGISTRATION: The study
      protocol is retrospectively registered at ClinicalTrials.gov as ID: NCT02937259 .

PMID- 29017472
TI  - Knowledge, attitude and behaviour towards the use of insecticide treated mosquito
      nets among pregnant women and children in rural Southwestern Uganda.
AB  - BACKGROUND: The burden of malaria in Uganda remains unacceptably high, especially
      among children and pregnant women. To prevent malaria related complications,
      household possession and use of Insecticide Treated mosquito Nets (ITNs) has
      become a common practice in the country. Despite the availability of ITNs,
      malaria remains a foremost public health concern in Uganda. We sought to explore
      knowledge, attitude, and behaviour towards the use of ITNs as a nightly malaria
      prevention strategy among pregnant women and children under five years of age in
      Isingiro district, Southwestern Uganda. MATERIALS AND METHODS: This was a
      community based, descriptive cross-sectional study, in which households with
      children under 5 years, and/or pregnant women were enrolled. We used a structured
      questionnaire to collect data on participants' understanding of the causes, signs
      and symptoms of malaria; use of ITNs to prevent malaria; attitudes and behaviours
      towards the use of ITNs. We also conducted key informant interviews (KIIs) to get
      in-depth understanding of responses from the participants. We analysed
      quantitative data using STATA version 12.Qualitative findings from the KIIs were
      transcribed and translated, and manually analysed using thematic content
      analysis. RESULTS: Of the 369 households enrolled, 98.4% (N = 363) households had
      children under five. Most participants (41.2%, N = 152) were in the 21-30 age
      category (mean age; 32.2 years). 98.1% (N = 362) of the respondents considered
      ITNs a key malaria prevention strategy. The ITN possession rate was 84.0% (N =
      310), of these, 66.1% (N = 205) consistently used them. 39% of the respondents
      did not have a positive attitude towards ITNs. CONCLUSIONS: Although 84.0% of the
      respondents possessed ITNs, many were not consistently using them. To this, there
      is need to engage all stakeholders (including cultural leaders, community health
      workers, religious leaders and the government) in the malaria prevention
      campaigns using ITNs through: a) government's concerted effort to ensure
      universal access of right fit ITNs, b) end-user directed health education to
      emphasize positive attributes of ITN use, c) telling the ITN success stories to
      improve on the usage.

PMID- 29017473
TI  - Australian consumer perspectives, attitudes and behaviours on antibiotic use and
      antibiotic resistance: a qualitative study with implications for public health
      policy and practice.
AB  - BACKGROUND: Consumers receive over 27 million antibiotic prescriptions annually
      in Australian primary healthcare. Hence, consumers are a key group to engage in
      the fight against antibiotic resistance. There is a paucity of research
      pertaining to consumers in the Australian healthcare environment. This study
      aimed to investigate the perspectives, attitudes and behaviours of Australian
      consumers on antibiotic use and antibiotic resistance, to inform national
      programs for reducing inappropriate antibiotic consumption. METHOD: Semi
      structured interviews with 32 consumers recruited via convenience and snowball
      sampling from a university population in South East Queensland. Interview
      transcripts were deductively and inductively coded. Main themes were identified
      using iterative thematic analysis. RESULTS: Three themes emerged from the
      analysis, to elucidate factors affecting antibiotic use: (a) prescription type;
      (b) consumer attitudes, behaviours, skills and knowledge; and (c) consumer
      engagement with antibiotic resistance. Consumers held mixed views regarding the
      use of delayed antibiotic prescriptions, and were often not made aware of the use
      of repeat antibiotic prescriptions. Consumers with regular general practitioners
      were more likely to have shared expectations regarding minimising the use of
      antibiotics. Even so, advice or information mediated by general practitioners was
      influential with all consumers; and helped to prevent inappropriate antibiotic
      use behaviours. Consumers were not aware of the free Return of Unwanted Medicines
      service offered by pharmacies and disposed of leftover antibiotics through
      household waste. To engage with mitigating antibiotic resistance, consumers
      required specific information. Previous public health campaigns raising awareness
      of antibiotics were largely not seen by this sample of consumers. CONCLUSIONS:
      Australian consumers have specific information needs regarding prescribed
      antibiotics to enable appropriate antibiotic use behaviours. Consumers also have
      expectations for high quality general practice consults conducted in a manner
      that increases consumer confidence in the treatment decision, regardless of
      whether an antibiotic is prescribed. To reduce inappropriate consumption of
      antibiotics and to more fully engage Australian consumers in mitigating
      antibiotic resistance, changes in health policy and practice are required.

PMID- 29017474
TI  - The disease burden of suicide in Ecuador, a 15 years' geodemographic cross
      sectional study (2001-2015).
AB  - BACKGROUND: Suicide affects people from different backgrounds, ethnical groups,
      socio-economic status and geographical locations. In Latin America, suicide
      reports arescarce, specially in Andean countries. In Ecuador, very few reports
      have partially described this phenomenon, nonetheless, estimation of the burden
      of disease (BoD) hasnever been reported in the country. METHODS: A country-wide
      comparison was performed using the Ministry of Public Health's national databases
      of overall mortality, Hospital Discharges Database, and the Population Census of
      the National Institute of Census and Statistics (INEC). The study variables
      analyzed were age, geographical distribution to provincial level, sex, means of
      suicide, educational attainment, marital status and mortality. Linear Regression
      and relative Risk analysis were used to predict outcome and the likelihood that
      suicide occur among study variables. RESULTS: In the last 15 years, 13,024
      suicides were officially reported. Men were 3 times more likely than women to die
      by suicide. The overall age-adjusted suicide ratio in Ecuador corresponds to 7.1
      per 100,000 per year. The sex-specific rates were 5.3 in women and 13.2 in men.
      The primary mean of suicide was hanging X70 (51.1%), followed by self-poisoning
      X68-X69 (35.2%) and firearms X72-X74 (7.6%). Provinces located at higher altitude
      reported higher rates than those located at sea level (9 per 100,000 vs 4.5 per
      100.000). The total economic loss due to suicide was estimated to be $852.6
      million during the 15 years' analysis. CONCLUSIONS: This is the first
      geodemographic study exploring the complete burden of suicide in Ecuador and one
      of the very few in Latin-America. In the last 15 years of available data, Ecuador
      ranks above the regional average with an adjusted suicide rate of 7.1 per 100,000
      inhabitants. An important finding is that Suicide affects rather younger
      populations, adding more than 10,000 years of premature years of life lost (YYL)
      between 2001 and 2015, becoming the first and fourth leading cause of death among
      adolescent women and men respectively. Suicide affects people from different
      backgrounds, socioeconomic status and educational attainment. The mean of suicide
      changed over time showing that gun and pesticides related deaths decreased
      significantly since 2001, while hanging and suffocation increased in more than
      50%.

PMID- 29017475
TI  - Reliability, validity and responsiveness of the German self-reported foot and
      ankle score (SEFAS) in patients with foot or ankle surgery.
AB  - BACKGROUND: Patient-reported outcome measures are a critical tool in evaluating
      the efficacy of orthopedic procedures and are increasingly used in clinical
      trials to assess outcomes of health care. The intention of this study was to
      develop and culturally adapt a German version of the Self-reported Foot and Ankle
      Score (SEFAS) and to evaluate reliability, validity and responsiveness. METHODS:
      According to Cross Cultural Adaptation of Self-Reported Measure guidelines
      forward and backward translation has been performed. The German SEFAS was
      investigated in 177 consecutive patients. 177 Patients completed the German
      SEFAS, Foot and Ankle Outcome Score (FAOS), Short-Form 36 and numeric scales for
      pain and disability (NRS) before and 118 patients 6 months after foot or ankle
      surgery. Test-Retest reliability, internal consistency, floor and ceiling
      effects, construct validity and minimal important change were analyzed. RESULTS:
      The German SEFAS demonstrated excellent test-retest reliability with ICC values
      of 0.97. Cronbach's alpha (alpha) value of 0.89 demonstrated strong internal
      consistency. No floor or ceiling effects were observed for the German version of
      the SEFAS. As hypothesized SEFAS correlated strongly with FAOS and SF-36 domains.
      It showed moderate (ES/SRM > 0.5) responsiveness between preoperative assessment
      and postoperative follow-up. CONCLUSION: The German version of the SEFAS
      demonstrated good psychometric properties. It proofed to be a valid and reliable
      instrument for use in foot and ankle patients. TRIAL REGISTRATION: DRKS00007585.

PMID- 29017476
TI  - The relationship between preoperative American Society of Anesthesiologists
      Physical Status Classification scores and functional recovery following hip
      fracture surgery.
AB  - BACKGROUND: Little is known about the relationship of the American Society of
      Anesthesiologists Physical Status Classification scores (ASA scores) on patient
      outcomes following hip fracture surgery in Asian countries. Therefore, this study
      explored the association of patients' preoperative ASA scores on trajectories of
      recovery in physical functioning and health outcomes during the first year
      following postoperative discharge for older adults with hip-fracture surgery in
      Taiwan. METHODS: The data for this study was generated from three prior studies.
      Participants (N = 226) were older hip-fracture patients from an observational
      study (n = 86) and two clinical trials (n = 61 and n = 79). Participants were
      recruited from the trauma wards of one medical center in northern Taiwan and data
      was collected prior to discharge and at 1, 3, 6, and 12 months after hospital
      discharge. Participants were grouped as ASA class 1-2 (50.5%; ASA Class 1, n = 7;
      ASA Class 2, n = 107) and ASA class 3 (49.5%, n = 112). Measures for mortality,
      service utilization, activities of daily living (ADL), measured by the Chinese
      Barthel Index, and health related quality of life, measured by Medical Outcomes
      Study Short Form-36, were assessed for the two groups. Generalized estimating
      equations (GEE) were used to analyze the changes over time for the two groups.
      RESULTS: During the first year following hip-fracture surgery, ASA class 1-2
      participants had significantly fewer rehospitalizations (6%, p = .02) and better
      scores for mental health (mean = 70.29, standard deviation = 19.03) at 6- and 12
      months following discharge than those classified as ASA 3. In addition, recovery
      of walking ability (70%, p = .001) and general health (adjusted mean = 58.31, p =
      .003) was also significantly better than ASA 3 participants. CONCLUSIONS: There
      was a significant association of hip-fracture patients classified as ASA 1-2 with
      better recovery and service utilization during the first year following surgery.
      Interventions for hip fractured patients with high ASA scores should be developed
      to improve recovery and quality of life.

PMID- 29017477
TI  - Mechanism of worsening diabetic retinopathy with rapid lowering of blood glucose:
      the synergistic hypothesis.
AB  - Insulin treatment has been associated with a paradoxical worsening of diabetes
      retinopathy since many years in European cohorts. Recently, this issue has been
      stressed by some studies conducted in other parts of the world. However, the
      mechanism underlying such evolution is not well understood. An osmotic theory has
      been evocated but failed to explain the clinical features of the disease.
      Considering recent findings from basic and clinical research, we discuss the
      possibility of a synergistic hypothesis based on the simultaneous action of
      insulin and vascular endothelial growth factor on eye blood vessels. We postulate
      that exogenous insulin could act synergistically with the vascular endothelial
      growth factor expressed by ischemic retina so as to trigger vascular
      proliferation and the worsening of diabetes retinopathy.

PMID- 29017478
TI  - Effectiveness of pulmonary rehabilitation in patients with interstitial lung
      disease of different etiology: a multicenter prospective study.
AB  - BACKGROUND: Recent evidences show that Pulmonary Rehabilitation (PR) is effective
      in patients with Interstitial Lung Disease (ILD). It is still unclear whether
      disease severity and/or etiology might impact on the reported benefits. We
      designed this prospective study 1) to confirm the efficacy of rehabilitation in a
      population of patients with ILDs and 2) to investigate whether baseline exercise
      capacity, disease severity or ILD etiology might affect outcomes. METHODS: Forty
      one patients (IPF 63%, age 66.9 +/- 11 ys) were enrolled in a standard PR course
      in two centers. Lung function, incremental and endurance cyclo-ergometry, Six
      Minutes Walking Distance (6MWD), chronic dyspnea (Medical Research Council scale
      MRC) and quality of life (St. George Respiratory Questionnaire-SGRQ) were
      recorded before and at the end of PR to measure any pre-to-post change.
      Correlation coefficients between the baseline level of Diffuse Lung Capacity for
      Carbon monoxide (DLCO), Forced Vital Capacity (FVC), 6MWD, power developed during
      incremental endurance test, GAP index (in IPF patients only) and etiology (IPF or
      non-IPF) with the functional improvement at the 6MWDT (meters), at the
      incremental and endurance cyclo-ergometry (endurance time) and the HRQoL were
      assessed. RESULTS: Out of the 41 patients, 97% (n = 40) completed the PR course.
      Exercise performance (both at peak load and submaximal effort), symptoms (iso
      time dyspnea and leg fatigue), SGRQ and MRC significantly improved after PR (p <
      .001). Patients with lower baseline 6MWD showed greater improvement in 6MWD
      (Spearman r score = - .359, p = .034) and symptoms relief at SGRQ (r = -.315, p =
      .025) regardless of underlying disease. CONCLUSION: Present study confirms that
      comprehensive rehabilitation is feasible and effective in patients with ILD of
      different severity and etiology. The baseline submaximal exercise capacity
      inversely correlates with both functional and symptom gains in this heterogeneous
      population.

PMID- 29017479
TI  - Psychosocial benefits of workplace physical exercise: cluster randomized
      controlled trial.
AB  - BACKGROUND: While benefits of workplace physical exercise on physical health is
      well known, little is known about the psychosocial effects of such initiatives.
      This study evaluates the effect of workplace versus home-based physical exercise
      on psychosocial factors among healthcare workers. METHODS: A total of 200 female
      healthcare workers (Age: 42.0, BMI: 24.1) from 18 departments at three hospitals
      were cluster-randomized to 10 weeks of: 1) home-based physical exercise (HOME)
      performed alone during leisure time for 10 min 5 days per week or 2) workplace
      physical exercise (WORK) performed in groups during working hours for 10 min 5
      days per week and up to 5 group-based coaching sessions on motivation for regular
      physical exercise. Vitality and mental health (SF-36, scale 0-100), psychosocial
      work environment (COPSOQ, scale 0-100), work- and leisure disability (DASH, 0
      100), control- (Bournemouth, scale 0-10) and concern about pain (Pain
      Catastrophizing Scale, scale 0-10) were assessed at baseline and at 10-week
      follow-up. RESULTS: Vitality as well as control and concern about pain improved
      more following WORK than HOME (all p < 0.05) in spite of increased work pace (p <
      0.05). Work- and leisure disability, emotional demands, influence at work, sense
      of community, social support and mental health remained unchanged. Between-group
      differences at follow-up (WORK vs. HOME) were 7 [95% confidence interval (95% CI)
      3 to 10] for vitality, -0.8 [95% CI -1.3 to -0.3] for control of pain and -0.9
      [95% CI -1.4 to -0.5] for concern about pain, respectively. CONCLUSIONS:
      Performing physical exercise together with colleagues during working hours was
      more effective than home-based exercise in improving vitality and concern and
      control of pain among healthcare workers. These benefits occurred in spite of
      increased work pace. TRIAL REGISTRATION: NCT01921764 at ClinicalTrials.gov .
      Registered 10 August 2013.

PMID- 29017481
TI  - Cognitive behavioral group therapy for patients with physical diseases and
      comorbid depressive or adjustment disorders on a waiting list for individual
      therapy: results from a randomized controlled trial.
AB  - BACKGROUND: Depressive and adjustment disorders are highly prevalent in patients
      with physical diseases and are associated with poorer quality of life, increased
      morbidity and mortality, as well as higher healthcare costs. Access to mental
      health care holds strong importance for these patients, although waiting times
      for outpatient individual psychotherapy in Germany are often long. Attending an
      intervention while waiting for individual therapy could improve this problem. For
      this purpose, we developed an eight-session cognitive behavioral group therapy
      (STEpS) and tested its efficacy in a randomized controlled trial. METHODS:
      Seventy-six patients with chronic physical diseases and comorbid depressive or
      adjustment disorders were randomized to either STEpS or a waiting list control
      group. The primary outcome was self-reported depression measured by the Hospital
      Anxiety and Depression Scale (HADS-D), while the secondary outcomes included
      global psychological distress and health-related quality of life. Data was
      assessed at baseline, post-treatment and 2-month follow-up and was analyzed based
      on intention-to-treat. RESULTS: Compared to the control group, the STEpS group
      showed significantly less depression (d = 0.37; p = .009) and significantly
      higher quality of life (mental: d = 0.47; p = .030; physical: d = 0.70; p = .001)
      at post-treatment. The groups did not differ in global psychological distress. At
      2-month follow-up, the STEpS group indicated significantly higher subjective
      physical health (d = 0.43; p = .046), but did not differ from the control group
      in the remaining outcomes. CONCLUSIONS: STEpS proved effective in improving
      depression and health-related quality of life in the short term but did not
      reveal effects on mental outcomes at 2-month follow-up. Nonetheless, the
      implementation of STEpS as a waiting list intervention prior to individual
      therapy could help patients to handle long waiting periods in outpatient care.
      TRIAL REGISTRATION: German Clinical Trials Register DRKS00005140 (27 August
      2013).

PMID- 29017480
TI  - Longitudinal assessment of daily activity patterns on weight change after
      involuntary job loss: the ADAPT study protocol.
AB  - BACKGROUND: The World Health Organization has identified obesity as one of the
      most visible and neglected public health problems worldwide. Meta-analytic
      studies suggest that insufficient sleep increases the risk of developing obesity
      and related serious medical conditions. Unfortunately, the nationwide average
      sleep duration has steadily declined over the last two decades with 25% of U.S.
      adults reporting insufficient sleep. Stress is also an important indirect factor
      in obesity, and chronic stress and laboratory-induced stress negatively impact
      sleep. Despite what we know from basic sciences about (a) stress and sleep and
      (b) sleep and obesity, we know very little about how these factors actually
      manifest in a natural environment. The Assessing Daily Activity Patterns Through
      Occupational Transitions (ADAPT) study tests whether sleep disruption plays a key
      role in the development of obesity for individuals exposed to involuntary job
      loss, a life event that is often stressful and disrupting to an individual's
      daily routine. METHODS: This is an 18-month closed, cohort research design
      examining social rhythms, sleep, dietary intake, energy expenditure, waist
      circumference, and weight gain over 18 months in individuals who have sustained
      involuntary job loss. Approximately 332 participants who lost their job within
      the last 3 months are recruited from flyers within the Arizona Department of
      Economic Security (AZDES) Unemployment Insurance Administration application
      packets and other related postings. Multivariate growth curve modeling will be
      used to investigate the temporal precedence of changes in social rhythms, sleep,
      and weight gain. DISCUSSION: It is hypothesized that: (1) unemployed individuals
      with less consistent social rhythms and worse sleep will have steeper weight gain
      trajectories over 18 months than unemployed individuals with stable social
      rhythms and better sleep; (2) disrupted sleep will mediate the relationship
      between social rhythm disruption and weight gain; and (3) reemployment will be
      associated with a reversal in the negative trajectories outlined above. Positive
      findings will provide support for the development of obesity prevention campaigns
      targeting sleep and social rhythms in an accessible subgroup of vulnerable
      individuals.

PMID- 29017482
TI  - Gender differences in factors associated with smartphone addiction: a cross
      sectional study among medical college students.
AB  - BACKGROUND: Smartphones are becoming increasingly indispensable in everyday life
      for most undergraduates in China, and this has been associated with problematic
      use or addiction. The aim of the current study was to investigate the prevalence
      of smartphone addiction and the associated factors in male and female
      undergraduates. METHODS: This cross-sectional study was conducted in 2016 and
      included 1441 undergraduate students at Wannan Medical College, China. The
      Smartphone Addiction Scale short version (SAS-SV) was used to assess smartphone
      addiction among the students, using accepted cut-offs. Participants' demographic,
      smartphone usage, and psycho-behavioral data were collected. Multivariate
      logistic regression models were used to seek associations between smartphone
      addiction and independent variables among the males and females, separately.
      RESULTS: The prevalence of smartphone addiction among participants was 29.8%
      (30.3% in males and 29.3% in females). Factors associated with smartphone
      addiction in male students were use of game apps, anxiety, and poor sleep
      quality. Significant factors for female undergraduates were use of multimedia
      applications, use of social networking services, depression, anxiety, and poor
      sleep quality. CONCLUSIONS: Smartphone addiction was common among the medical
      college students investigated. This study identified associations between
      smartphone usage, psycho-behavioral factors, and smartphone addiction, and the
      associations differed between males and females. These results suggest the need
      for interventions to reduce smartphone addiction among undergraduate students.

PMID- 29017484
TI  - Solar UV exposure among outdoor workers in Denmark measured with personal UV-B
      dosimeters: technical and practical feasibility.
AB  - BACKGROUND: Exposure to solar ultraviolet radiation is a well-known cause of skin
      cancer. This is problematic for outdoor workers. In Denmark alone, occupational
      skin cancer poses a significant health and safety risk for around 400,000 outdoor
      workers. Objective measures of solar ultraviolet radiation exposure are needed to
      help resolve this problem. This can be done using personal ultraviolet radiation
      dosimeters. METHODS: We consider technical and practical feasibility of measuring
      individual solar ultraviolet exposure at work and leisure in professions with
      different a priori temporal high-level outdoor worktime, using aluminium gallium
      nitride (AlGaN) photodiode detector based personal UV-B dosimeters. Essential
      technical specifications including the spectral and angular responsivity of the
      dosimeters are described and pre-campaign dosimeter calibration applicability is
      verified. The scale and conduct of dosimeter deployment and campaign in-field
      measurements including failures and shortcomings affecting overall data
      collection are presented. RESULTS: Nationwide measurements for more than three
      hundred and fifty workers from several different professions were collected in
      the summer of 2016. On average, each worker's exposure was measured for a 2-week
      period, which included both work and leisure. Data samples of exposure at work
      during a Midsummer day show differences across professions. A construction worker
      received high-level occupational UV exposure most of the working day, except
      during lunch hour, accumulating to 5.1 SED. A postal service worker was exposed
      intermittently around noon and in the afternoon, preceded by no exposure forenoon
      when packing mail, accumulating to 1.6 SED. A crane fitter was exposed only
      during lunch hour, accumulating to 0.7 SED. These findings are in line with our
      specialist knowledge as occupational physicians. CONCLUSIONS: Large-scale use of
      personal UV-B dosimeters for measurement of solar ultraviolet radiation exposure
      at work and leisure in Denmark is indeed feasible from a technical and practical
      viewpoint. Samples of exposure data shown support the presumption that the Danish
      campaign UV-B dosimeter measurement dataset can be used to sum and compare
      exposure between groups of professions with reliable results to be used in future
      analysis with clinical as well as epidemiological/questionnaire data. This was
      despite some dosimeter failures and shortcomings.

PMID- 29017483
TI  - Co-infection of Schistosoma mansoni/hepatitis C virus and their associated
      factors among adult individuals living in fishing villages, north-western
      Tanzania.
AB  - BACKGROUND: Schistosoma mansoni and Hepatitis C virus (HCV) are co-existence in
      sub-Saharan Africa and co-infection is common among humans population. The
      immunological responses characterized with Th2-immune responses for S. mansoni
      and Th1-immune responses for HCV are responsible for development hepatic
      morbidities in infected individuals. However, the co-occurrences of S. mansoni
      and HCV infection, their related ultrasound detectable morbidities and associated
      risk factors at community levels have not been examined in fishing communities,
      north-western Tanzania. In this context, the present study covers that gap.
      METHODS: A cross-sectional study was conducted among 1924 asymptomatic
      individuals aged 15-55 years in four fishing villages (Igombe, Igalagala,
      Sangabuye and Kayenze) of Northwestern Tanzania. A single stool sample was
      collected from each study participants and examined for S. mansoni eggs using
      Kato Katz technique. Hepatitis C surface antigen (HCVsAg) was determined from a
      finger prick blood sample using a rapid test. RESULTS: Overall, 51.8% (997/1924;
      95%CI: 49.6-54.1) of the study participants were infected with S. mansoni and had
      a mean intensity of 223.7epg (95%; 202.4-247.1). Of the study participants, 90
      (4.7%) were infected with hepatitis C virus (HCV). Overall, 2. 4% (47/1924) of
      the study participants were co-infected with S. mansoni and hepatitis C virus.
      Among the co-infected individuals, 42.6%, 70.2% and 19.1% had splenomegaly,
      hepatomegaly and periportal fibrosis (PPF). Factors associated with S.
      mansoni/HCV co-infection were being aged 26-35 years (aRR = 2.67, 95%CI: 1.03
      6.93, P < 0.04), 46-55 years (aRR = 2.89, 95%CI: 1.10-7.57, P < 0.03) and having
      marked hepatomegaly (aRR = 2.32, 95%CI: 1.09-4.9, P < 0.03). CONCLUSION: In this
      setting, S. mansoni and Hepatitis C are co-endemic and a proportion of
      individuals were co-infected. Hepatosplenic morbidities characterized with
      hepatomegaly, splenomegaly, hepatosplenomegaly and PPF were observed in co
      infected individuals. These results highlight the need for integrated
      interventions measures against parasitic and viral diseases.

PMID- 29017485
TI  - Bidens pilosa Ethylene acetate extract can protect against L-NAME-induced
      hypertension on rats.
AB  - BACKGROUND: Essential hypertension is mainly caused by endothelial dysfunction
      which results from nitric oxide (NO) deficiency. The present study was design to
      evaluate the protective effect of Bidens pilosa ethylene acetate extract (Bp) on
      L-NAME induced hypertension and oxidative stress in rats. METHODS: Male Wistar
      rats were used to induce hypertension by the administration of L-NAME (a non
      pecific nitric oxide inhibitor) (50 mg/kg/day). The others groups were receiving
      concomitantly L-NAME plus Bp extract (75 and 150 mg/kg/day) or losartan (25
      mg/kg/day). All the treatments were given orally for 4 weeks. At the end of the
      treatment, the hemodynamic parameters were recorded using the direct cannulation
      method. The effects of the extract on lipid profile, kidney and liver functions
      as well as oxidative stress markers were evaluated by colorimetric method.
      Results were expressed as the mean +/- SEM. The difference between the groups was
      compared using one-way analysis of variance (ANOVA) followed by the Duncan's post
      hoc test. RESULTS: Animals receiving L-NAME presented high blood pressure, normal
      heart rate and lipid profile as well as NO depletion, liver and kidney injuries
      and oxidative stress. The concomitant treatment with L-NAME and Bp or losartan
      succeeded to prevent the raised of blood pressure and all the other injuries
      without affecting the heart rate. CONCLUSION: These results confirm the
      antihypertensive effects of Bidens pilosa and highlight its protective properties
      in L-NAME model of hypertension in rat, probably due to the presence of Quercetin
      3,3 '-dimethyl ether 7-0-beta-D-glucopyranoside.

PMID- 29017486
TI  - Limits to human enhancement: nature, disease, therapy or betterment?
AB  - BACKGROUND: New technologies facilitate the enhancement of a wide range of human
      dispositions, capacities, or abilities. While it is argued that we need to set
      limits to human enhancement, it is unclear where we should find resources to set
      such limits. DISCUSSION: Traditional routes for setting limits, such as referring
      to nature, the therapy-enhancement distinction, and the health-disease
      distinction, turn out to have some shortcomings. However, upon closer scrutiny
      the concept of enhancement is based on vague conceptions of what is to be
      enhanced. Explaining why it is better to become older, stronger, and more
      intelligent presupposes a clear conception of goodness, which is seldom provided.
      In particular, the qualitative better is frequently confused with the
      quantitative more. We may therefore not need "external" measures for setting its
      limits - they are available in the concept of enhancement itself. While there may
      be shortcomings in traditional sources of limit setting to human enhancement,
      such as nature, therapy, and disease, such approaches may not be necessary. The
      specification-of-betterment problem inherent in the conception of human
      enhancement itself provides means to restrict its unwarranted proliferation. We
      only need to demand clear, sustainable, obtainable goals for enhancement that are
      based on evidence, and not on lofty speculations, hypes, analogies, or weak
      associations. Human enhancements that specify what will become better, and
      provide adequate evidence, are good and should be pursued. Others should not be
      accepted.

PMID- 29017487
TI  - Curcumin is a promising inhibitor of genotype 2 porcine reproductive and
      respiratory syndrome virus infection.
AB  - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) could
      lead to pandemic diseases and huge financial losses to the swine industry
      worldwide. Curcumin, a natural compound, has been reported to serve as an entry
      inhibitor of hepatitis C virus, chikungunya virus and vesicular stomatitis virus.
      In this study, we investigated the potential effect of curcumin on early stages
      of PRRSV infection. RESULTS: Curcumin inhibited infection of Marc-145 cells and
      porcine alveolar macrophages (PAMs) by four different genotype 2 PRRSV strains,
      but had no effect on the levels of major PRRSV receptor proteins on Marc-145
      cells and PAMs or on PRRSV binding to Marc-145 cells. However, curcumin did block
      two steps of the PRRSV infection process: virus internalization and virus
      mediated cell fusion. CONCLUSIONS: Our results suggested that an inhibition of
      genotype 2 PRRSV infection by curcumin is virus strain-independent, and mainly
      inhibited by virus internalization and cell fusion mediated by virus.
      Collectively, these results demonstrate that curcumin holds promise as a new anti
      PRRSV drug.

PMID- 29017489
TI  - Erratum to: BMC Palliative Care, Vol. 17.

PMID- 29017488
TI  - Understanding collaborative care implementation in the Department of Veterans
      Affairs: core functions and implementation challenges.
AB  - BACKGROUND: The collaborative care model is an evidence-based practice for
      treatment of depression in which designated care managers provide clinical
      services, often by telephone. However, the collaborative care model is
      infrequently adopted in the Department of Veterans Affairs (VA). Almost all VA
      medical centers have adopted a co-located or embedded approach to integrating
      mental health care for primary care patients. Some VA medical centers have also
      adopted a telephone-based collaborative care model where depression care managers
      support patient education, patient activation, and monitoring of adherence and
      progress over time. This study evaluated two research questions: (1) What does a
      dedicated care manager offer in addition to an embedded-only model? (2) What are
      the barriers to implementing a dedicated depression care manager? METHODS: This
      study involved 15 qualitative, multi-disciplinary, key informant interviews at
      two VA medical centers where reimbursement options were the same- both with
      embedded mental health staff, but one with a depression care manager. Participant
      interviews were recorded and transcribed. Thematic analysis was used to identify
      descriptive and analytical themes. RESULTS: Findings suggested that some of the
      core functions of depression care management are provided as part of embedded
      only mental health care. However, formal structural attention to care management
      may improve the reliability of care management functions, in particular
      monitoring of progress over time. Barriers to optimal implementation were
      identified at both sites. Themes from the care management site included finding
      assertive care managers to hire, cross-discipline integration and collaboration,
      and primary care provider burden. Themes from interviews at the embedded site
      included difficulty getting care management on leaders' agendas amidst competing
      priorities and logistics (staffing and space). CONCLUSIONS: Providers and
      administrators see depression care management as a valuable healthcare service
      that improves patient care. Barriers to implementation may be addressed by team
      building interventions to improve cross-discipline integration and communication.
      Findings from this study are limited in scope to the VA healthcare system. Future
      investigation of whether alternative barriers exist in implementation of
      depression care management programs in non-VA hospital systems, where
      reimbursement rates may be a more prominent concern, would be valuable.

PMID- 29017490
TI  - Germline mutation within COL2A1 associated with lethal chondrodysplasia in a
      polled Holstein family.
AB  - BACKGROUND: The bulldog calf syndrome is a lethal form of the inherited
      congenital chondrodysplasias. Among the progeny of the polled Holstein bull
      Energy P cases of lethal chondrodysplasia were observed. Pedigrees of the cases
      and the frequency of 3/8 cases among the offspring of Energy P at our teaching
      and experimental farm Ruthe (LuFG Ruthe) supported the assumption of a germline
      mutation with a mosaic of normal and defective sperm. RESULTS: All three
      malformed calves were examined using necropsy, histopathology and computed
      tomography scanning. The phenotypic appearance of the affected calves was highly
      similar; they presented with severe disproportionate dwarfism and reduced body
      weight. The syndrome was characterized by brachygnathia superior, bilateral
      palatoschisis, shortening and compression of the body due to malformed vertebrae,
      in their size reduced and malformed ribs and reduced length of the long bones of
      the limbs. The bones had small irregular diaphyses and enlarged epiphyses. Whole
      genome sequencing of one bulldog calf, sperm of its sire Energy P and a normal
      progeny of Energy P identified a deleterious missense mutation (g.32476082G > A,
      c.2986G > A, ss2019324576) within COL2A1 on bovine chromosome (BTA) 5. Sanger
      sequencing confirmed the ss2019324576 variant in the affected calves and sperm of
      Energy P. This mutation is located within the collagen triple helix repeat and
      causes an exchange of glycine to serine (p.996G > S) in COL2A1. This private
      single nucleotide variant (SNV) was present as a gonadal mosaic in sperm of the
      bull. All affected calves were in a heterozygous state whereas normal half
      siblings and all dams of the progeny from Energy P were missing this SNV.
      Validation in polled Holstein bulls and normal Holstein calves randomly sampled
      from several herds and from the LuFG Ruthe confirmed this SNV as private.
      CONCLUSIONS: The identified spontaneous missense mutation within COL2A1 is most
      likely the cause of lethal chondrodysplasia in the progeny of Energy P through a
      dominant negative effect. This example suggests that it would be beneficial to
      conduct whole genome sequencing of sperm from bulls widely used in artificial
      insemination in order to detect germline mosaicism.

PMID- 29017491
TI  - Spatial model for risk prediction and sub-national prioritization to aid
      poliovirus eradication in Pakistan.
AB  - BACKGROUND: Pakistan is one of only three countries where poliovirus circulation
      remains endemic. For the Pakistan Polio Eradication Program, identifying high
      risk districts is essential to target interventions and allocate limited
      resources. METHODS: Using a hierarchical Bayesian framework we developed a
      spatial Poisson hurdle model to jointly model the probability of one or more
      paralytic polio cases, and the number of cases that would be detected in the
      event of an outbreak. Rates of underimmunization, routine immunization, and
      population immunity, as well as seasonality and a history of cases were used to
      project future risk of cases. RESULTS: The expected number of cases in each
      district in a 6-month period was predicted using indicators from the previous 6
      months and the estimated coefficients from the model. The model achieves an
      average of 90% predictive accuracy as measured by area under the receiver
      operating characteristic (ROC) curve, for the past 3 years of cases. CONCLUSIONS:
      The risk of poliovirus has decreased dramatically in many of the key reservoir
      areas in Pakistan. The results of this model have been used to prioritize sub
      national areas in Pakistan to receive additional immunization activities,
      additional monitoring, or other special interventions.

PMID- 29017492
TI  - Electroacupuncture ameliorating post-stroke cognitive impairments via inhibition
      of peri-infarct astroglial and microglial/macrophage P2 purinoceptors-mediated
      neuroinflammation and hyperplasia.
AB  - BACKGROUND: During ischemic stroke (IS), adenosine 5'-triphosphate (ATP) is
      released from damaged nerve cells of the infract core region to the extracellular
      space, invoking peri-infarct glial cellular P2 purinoceptors singling, and
      causing pro-inflammatory cytokine secretion, which is likely to initiate or
      aggravate motor and cognitive impairment. It has been proved that
      electroacupuncture (EA) is an effective and safe strategy used in anti
      inflammation. However, EA for the role of purine receptors in the central nervous
      system has not yet been reported. METHODS: Ischemia-reperfusion injured rat model
      was induced by middle cerebral artery occlusion and reperfusion (MCAO/R). EA
      treatment at the DU 20 and DU 24 acupoints treatment were conducted to rats from
      the 12 h after MCAO/R injury for consecutive 7 days. The neurological outcomes,
      infarction volumes and the level of astroglial and microglial/macrophage
      hyperplasia, inflammatory cytokine and P2X7R and P2Y1R expression in the peri
      infarct hippocampal CA1and sensorimotor cortex were investigated after IS to
      evaluate the MCAO/R model and therapeutic mechanism of EA treatment. RESULTS: EA
      effectively reduced the level of pro-inflammatory cytokine interleukin-1beta (IL
      1beta) as evidenced by reduction in astroglial and microglial/macrophage
      hyperplasia and the levels of P2X7R and ED1, P2X7R and GFAP, P2Y1R and ED1, P2Y1R
      and GFAP co-expression in peri-infarct hippocampal CA1 and sensorimotor cortex
      compared with that of MCAO/R model and Non-EA treatment, accompanied by the
      improved neurological deficit and the motor and memory impairment outcomes.
      Therefore, our data support the hypothesis that EA could exert its anti
      inflammatory effect via inhibiting the astroglial and microglial/macrophage P2
      purinoceptors (P2X7R and P2Y1R)-mediated neuroinflammation after MCAO/R injury.
      CONCLUSION: Astroglial and microglial/macrophage P2 purinoceptors-mediated
      neuroinflammation and hyperplasia in peri-infarct hippocampal CA1 and
      sensorimotor cortex were attenuated by EA treatment after ischemic stroke
      accompanied by the improved motor and memory behavior performance.

PMID- 29017493
TI  - Enzalutamide versus abiraterone as a first-line endocrine therapy for castration
      resistant prostate cancer (ENABLE study for PCa): a study protocol for a
      multicenter randomized phase III trial.
AB  - BACKGROUND: Both enzalutamide and abiraterone have demonstrated improved
      radiographic progression-free and overall survival for castration-resistant
      prostate cancer (CRPC) compared with placebo controls before docetaxel treatment
      in phase III studies. These oral agents target androgen and androgen receptor
      signaling and are thought to be less toxic than chemotherapy. Cross-resistance to
      these agents was recently reported because of their similar mechanism of action,
      and it is important to assess which agent is more effective to use initially for
      CRPC. METHODS/DESIGN: The present study is a phase III, investigator-initiated,
      multicenter, head-to-head, randomized controlled trial investigating enzalutamide
      vs. abiraterone as a first-line treatment for CRPC patients. Patients will be
      randomly assigned to an enzalutamide or an abiraterone treatment group. The
      primary endpoint is the time to prostate-specific antigen progression. The target
      sample size is set at 100 patients per group (total, 200 patients). The study
      duration is 5 years, and the duration for recruitment is 2 years and 6 months.
      DISCUSSION: Thus far, there have been no prospective head-to-head studies
      comparing enzalutamide and abiraterone. This ENABLE study will clarify which
      agent should be prioritized for CRPC patients and enable clinicians to decide the
      appropriate treatment before chemotherapy. TRIAL REGISTRATION: University
      hospital Medical Information Network (UMIN) Center identifier UMIN000015529 .
      Registrated 11/1/2014.

PMID- 29017494
TI  - The impact of obesity on health-related quality of life in Spain.
AB  - BACKGROUND: It is well documented that obesity is strongly associated with
      mortality and morbidity, but less is known about its impact on functional status
      and health-related quality of life (HRQOL). The purpose of this study was to
      calculate the impact of the Body Mass Index (BMI) on the HRQOL of the Spanish
      adult population, with special emphasis on BMI >= 35. METHODS: We used the
      Spanish National Health Survey (SNHS) 2011-2012 to assess the statistical
      association between HRQOL, measured through the EuroQol-5D-5L questionnaire, and
      the BMI. We conducted linear regression analysis for the EuroQol-5D-5L Visual
      Analogue Scale (VAS) and probit regressions for each of the five dimensions of
      the EuroQol-5D-5L. RESULTS: Self-perceived problems in the five dimensions of the
      EuroQol-5D-5L increased along the BMI, especially in the mobility and
      pain/discomfort dimensions. Having a BMI >= 35 reduced HRQOL even in the absence
      of chronic diseases. After controlling for comorbidities, severe obesity
      decreased the VAS score by an average of 1.9 points and increased the probability
      of reporting any HRQOL problem in mobility (11.8%), self-care (2.2%), usual
      activities (4.3%) and pain/discomfort (7.4%). No association was found between
      obesity and mental problems. All the parameters analysed suggest that HRQOL in
      women and people aged 65 years and over was significantly worse than average.
      CONCLUSIONS: BMI is an explanatory factor of self-perceived quality of life.
      Obesity is associated with a worse HRQOL, especially in women and people aged
      over 64 years. These results may be useful for designing prevention or treatment
      health policies to target obesity among the Spanish population.

PMID- 29017495
TI  - Treatment of thoracic or lumbar burst fractures with Balloon Assisted Endplate
      Reduction using Tricalcium Phosphate cement: histological and radiological
      evaluation.
AB  - BACKGROUND: Short-segment pedicle-screw instrumentation is frequently used to
      stabilize thoracolumbar burst fractures. A recognized disadvantage of this
      procedure is recurrent kyphosis from intervertebral disc creep into the fractured
      central endplate. Balloon Assisted Endplate Reduction (BAER) using Tricalcium
      Phosphate bone cement (TCP) enables elevation of the centrally depressed
      endplate. Our objective was to evaluate the bone-tissue response to TCP and to
      analyse whether BAER using TCP can prevent recurrent kyphosis after removal of
      the instrumentation. METHODS: Fourteen patients with traumatic thoracolumbar
      burst fractures were operated with BAER using TCP in combination with short
      segment instrumentation. Nine months after surgery, instrumentation was removed
      and transpedicular biopsies were taken for histological and histochemical
      analysis. Roentgenograms pre- and postoperatively and at latest follow-up after
      removal of the instrumentation were evaluated. RESULTS: Average follow-up was 2.6
      years. Analysis of the biopsies showed a variable degree of bone remodelling with
      incorporation of TCP into newly formed bone matrix. No extensive foreign body
      reactions, inflammation, granulomatous responses or tissue necrosis were
      observed. Wedge-angle, kyphosis-angle and both the anterior-posterior and central
      posterior vertebral body height ratios improved significant postoperatively (p <
      0.001). After removal of the instrumentation no significant differences in wedge
      angle or height ratios were seen (p = 0.12). The kyphosis-angle increased four
      degrees (p = 0.01). CONCLUSION: TCP showed good histological osseointegration
      with no adverse events. TCP can therefore be safely used and could be beneficial
      in treatment of thoracolumbar burst fractures. BAER with TCP in combination with
      short-segment instrumentation might reduce recurrence of deformity even after
      removal of the instrumentation in comparison to short-segment instrumentation
      alone. TRIAL REGISTRATION: This study is registered at the at the Dutch Trial
      Registry (NTR3498).

PMID- 29017496
TI  - A novel interaction perturbation analysis reveals a comprehensive regulatory
      principle underlying various biochemical oscillators.
AB  - BACKGROUND: Biochemical oscillations play an important role in maintaining
      physiological and cellular homeostasis in biological systems. The frequency and
      amplitude of oscillations are regulated to properly adapt to environments by
      numerous interactions within biomolecular networks. Despite the advances in our
      understanding of biochemical oscillators, the relationship between the network
      structure of an oscillator and its regulatory function still remains unclear. To
      investigate such a relationship in a systematic way, we have developed a novel
      analysis method called interaction perturbation analysis that enables direct
      modulation of the strength of every interaction and evaluates its consequence on
      the regulatory function. We have applied this new method to the analysis of three
      representative types of oscillators. RESULTS: The results of interaction
      perturbation analysis showed different regulatory features according to the
      network structure of the oscillator: (1) both frequency and amplitude were seldom
      modulated in simple negative feedback oscillators; (2) frequency could be tuned
      in amplified negative feedback oscillators; (3) amplitude could be modulated in
      the incoherently amplified negative feedback oscillators. A further analysis of
      naturally-occurring biochemical oscillator models supported such different
      regulatory features according to their network structures. CONCLUSIONS: Our
      results provide a clear evidence that different network structures have different
      regulatory features in modulating the oscillation frequency and amplitude. Our
      findings may help to elucidate the fundamental regulatory roles of network
      structures in biochemical oscillations.

PMID- 29017499
TI  - Imported malaria in Spain (2009-2016): results from the +REDIVI Collaborative
      Network.
AB  - BACKGROUND: Imported malaria is a frequent diagnosis in travellers and migrants.
      The objective of this study was to describe the epidemiological and clinical
      characteristics of patients diagnosed with imported malaria within a Spanish
      collaborative network registering imported diseases (+REDIVI). In addition, the
      possible association between malaria and type of case, gender, age or area of
      exposure was explored. METHODS: Cases of imported malaria were identified among
      all cases registered in the +REDIVI database during the period October 2009
      October 2016. Demographic, epidemiological and clinical characteristics were
      analysed. RESULTS: In total, 11,816 cases of imported infectious diseases were
      registered in +REDIVI's database between October 2009 and October 2016.
      Immigrants seen for the first time after migration accounted for 60.2% of cases,
      21.0% of patients were travellers, and 18.8% were travellers/immigrants visiting
      friends and relatives (VFRs). There were 850 cases of malaria (850/11,816, 7.2%).
      Malaria was significantly more frequent in men than in women (56.8% vs 43.2%) and
      in VFR-immigrants (52.6%) as compared to travellers (21.3%), immigrants (20.7%)
      and VFR-travellers (5.4%) (p < 0.001). Although this data was not available for
      most patients with malaria, only a minority (29/217, 13.4%) mentioned correct
      anti-malarial prophylaxis. Sub-Saharan Africa was found to be the most common
      region of acquisition of malaria. Most common reason for consultation after
      travel was a febrile syndrome although an important proportion of immigrants were
      asymptomatic and presented only for health screening (27.3%). Around 5% of
      travellers presented with severe malaria. The most prevalent species of
      Plasmodium diagnosed was Plasmodium falciparum (81.5%). Malaria due to Plasmodium
      ovale/Plasmodium vivax was frequent among travellers (17%) and nearly 5% of all
      malaria cases in immigrants were caused by Plasmodium malariae. CONCLUSIONS:
      Malaria was among the five most frequent diagnoses registered in +REDIVI's
      database. Some significant differences were found in the distribution of malaria
      according to gender, type of case, species. Among all malaria cases, the most
      frequent diagnosis was P. falciparum infection in VFR-immigrant men.

PMID- 29017498
TI  - Glycated albumin and its variability as an indicator of cardiovascular autonomic
      neuropathy development in type 2 diabetic patients.
AB  - BACKGROUND: We investigated whether glycated albumin (GA) and its variability are
      associated with cardiovascular autonomic neuropathy (CAN) and further compared
      their associations with glycated hemoglobin (HbA1c). METHODS: This retrospective
      longitudinal study included 498 type 2 diabetic patients without CAN. CAN was
      defined as at least two abnormal results in parasympathetic tests or presence of
      orthostatic hypotension. The mean, standard deviation (SD), and coefficient of
      variance (CV) were calculated from consecutively measured GA (median 7 times) and
      HbA1c levels (median 8 times) over 2 years. Logistic regression analysis was used
      to compare the associations between CAN and GA- or HbA1c-related parameters.
      Receiver operating characteristic (ROC) curve analysis was used to compare the
      predictive power for CAN between GA- and HbA1c-related parameters. RESULTS: A
      total of 53 subjects (10.6%) developed CAN over 2 years. The mean, SD, and CV of
      GA or HbA1c were significantly higher in subjects with CAN. Higher mean GA and GA
      variability were associated with the risk of developing CAN, independent of
      conventional risk factors and HbA1c. In ROC curve analysis, the SD and CV of GA
      showed higher predictive value for CAN compared to the SD and CV of HbA1c,
      whereas the predictive value of mean GA did not differ from that of mean HbA1c.
      The mean, SD, and CV of GA showed additive predictive power to detect CAN
      development along with mean HbA1c. CONCLUSIONS: Higher serum GA and its
      variability are significantly associated with the risk of developing CAN. Serum
      GA might be a useful indicator for diabetic complications and can enhance HbA1c's
      modest clinical prediction for CAN.

PMID- 29017500
TI  - NF-kappaB potentiates tumor growth by suppressing a novel target LPTS.
AB  - BACKGROUND: Chronic inflammation is causally linked to the carcinogenesis and
      progression of most solid tumors. LPTS is a well-identified tumor suppressor by
      inhibiting telomerase activity and cancer cell growth. However, whether and how
      LPTS is regulated by inflammation signaling is still incompletely elucidated.
      METHODS: Real-time PCR and western blotting were used to determine the expression
      of p65 and LPTS. Reporter gene assay, electrophoretic mobility shift assay and
      chromatin immunoprecipitation were performed to decipher the regulatory mechanism
      between p65 and LPTS. Cell counting kit-8 assays and xenograt models were used to
      detect p65-LPTS-regulated cancer cell growth in vitro and in vivo, respectively.
      RESULTS: Here we for the first time demonstrated that NF-kappaB could inhibit
      LPTS expression in the mRNA and protein levels in multiple cancer cells (e.g.
      cervical cancer and colon cancer cells). Mechanistically, NF-kappaB p65 could
      bind to two consensus response elements locating at -1143/-1136 and -888/-881 in
      the promoter region of human LPTS gene according to EMSA and ChIP assays.
      Mutation of those two binding sites rescued p65-suppressed LPTS promoter
      activity. Functionally, NF-kappaB regulated LPTS-dependent cell growth of
      cervical and colon cancers in vitro and in xenograft models. In translation
      studies, we verified that increased p65 expression was associated with decreased
      LPTS level in multiple solid cancers. CONCLUSIONS: Taken together, we revealed
      that NF-kappaB p65 potentiated tumor growth via suppressing a novel target LPTS.
      Modulation of NF-kappaB-LPTS axis represented a potential strategy for treatment
      of those inflammation-associated malignancies.

PMID- 29017501
TI  - Psychometric properties of the Children's Response Styles Questionnaire in a Hong
      Kong Chinese community sample.
AB  - BACKGROUND: The Children's Response Styles Questionnaire (CRSQ) is a widely
      adopted inventory that assesses response styles in youths. It is useful in
      examining how coping styles (particularly rumination) may relate to depressive
      vulnerability in youths. Despite its utility, little is known about its
      applicability in non-Western cultures and CRSQ has not been evaluated using
      current psychometric methods including item response theory (IRT). The present
      study assessed the properties using IRT methods in a Chinese youth sample.
      METHODS: Students in Grades 4-6 were recruited from seven public primary schools
      in Hong Kong, and a total of 581 children (280 boys and 301 girls) between 8 and
      14 years of age participated in the study. A Chinese version of CRSQ was
      administered to them in groups at school after receiving written parental consent
      as well as students' assent. RESULTS: Confirmatory factor analysis revealed a two
      factor structure that was comparable to that identified in Western samples,
      namely, the rumination and distraction/problem-solving subscales. IRT analysis
      suggested that items varied in levels of item discrimination and item severity,
      and in precision/usefulness for assessing the underlying latent trait levels.
      Test information analysis indicated that rumination subscale was more useful than
      the distraction and problem-solving subscale in assessing the latent trait over a
      broader range of levels. For gender-based Differential Item Functioning (DIF)
      analysis, item 1 "When I am sad, I think about how alone I feel" was found to
      exhibit higher discriminating power for girls than boys. CONCLUSIONS: The study
      presents the first attempt to examine CRSQ item properties using IRT analysis and
      supports its validity beyond the Western cultures. The factor structure of CRSQ
      was found to be comparable to the West in our Chinese sample. Differential Item
      Functioning (DIF) evaluation suggested all but one item in the rumination
      subscale of the CRSQ apply equally well to both boys and girls.

PMID- 29017497
TI  - The effects of vildagliptin compared with metformin on vascular endothelial
      function and metabolic parameters: a randomized, controlled trial (Sapporo Athero
      Incretin Study 3).
AB  - BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors may have protective effects
      in the early stage of atherosclerosis in patients with type 2 diabetes, although
      similar effects in advanced atherosclerosis were not shown in recent randomized
      placebo-controlled studies. Therefore, we investigated the efficacy of DPP-4
      inhibitor on endothelial function and glycemic metabolism compared with high-dose
      metformin. METHODS: In this multicenter, open-labeled, prospective, randomized,
      parallel-group comparison study, patients with type 2 diabetes treated with low
      dose metformin (500-750 mg/day) were enrolled and randomly assigned to a
      vildagliptin, a DPP-4 inhibitor, add-on group (Vilda) or a double dose of
      metformin group (high Met) for 12 weeks. Flow-mediated dilation (FMD) and serum
      metabolic markers were assessed before and after treatment. In addition, glycemic
      control and metabolic parameters were also assessed. RESULTS: Ninety-seven
      subjects (aged 58.7 +/- 11.0 years; body mass index, 25.9 +/- 4.4 kg/m2; HbA1c,
      7.3 +/- 0.5%; FMD, 5.8 +/- 2.6%) were enrolled. Eight subjects dropped out by the
      end of the study. There were no significant differences between the two groups in
      baseline characteristics. After 12 weeks, HbA1c was significantly improved in the
      Vilda group compared with the high Met group (- 0.80 +/- 0.38% vs. - 0.40 +/-
      0.47%, respectively; p < 0.01). However, there were no significant differences in
      FMD (- 0.51 [- 1.08-0.06]% vs. - 0.58 [- 1.20-0.04]%). Although the
      apolipoprotein B/apolipoprotein A1 ratio was significantly reduced in the Vilda
      group compared with baseline (0.66-0.62; p < 0.01), the change did not differ
      significantly between the two groups (- 0.04 vs. 0.00; p = 0.27). Adiponectin
      levels were significantly increased in the Vilda group compared with the high Met
      group (0.75 MUg/mL vs. 0.01 MUg/mL; p < 0.01). CONCLUSIONS: Regardless of
      glycemic improvement, combination therapy of vildagliptin and metformin did not
      affect endothelial function but may exert favorable effects on adipokine levels
      and lipid profile in patients with type 2 diabetes without advanced
      atherosclerosis.

PMID- 29017502
TI  - The presence of residual gold nanoparticles in samples interferes with the RT
      qPCR assay used for gene expression profiling.
AB  - BACKGROUND: RT-qPCR is routinely used in expression profiling of toxicity pathway
      genes. However, genetic and molecular level studies used to determine, understand
      and clarify potential risks of engineered nanomaterials (ENMs) are still
      incomplete. Concerns regarding possible interference caused by intracellular ENMs
      during analyses have been raised. The aim of this study was to verify a qPCR
      procedure for gene expression assays, which can be used in toxicity and exposure
      assessments. RESULTS: Amplification of ten reference genes was performed to test
      the expression stability. A preliminary study was performed on RNA from BEAS-2B
      cells that had been treated with AuNPs. Also, a reference total RNA standard from
      ten cell lines was spiked with various amounts of the same AuNP. This treatment
      mimics exposure assessment studies, where assay-interference may be caused by
      intracellular residual ENMs still being present in the biological samples (during
      and after isolation/purification procedures). Both types of RNA samples were
      reverse transcribed and then amplified by qPCR. The qPCR-related software and
      statistical programs used included BestKeeper, NormFinder, REST and qBase+. These
      results proved that using standard qPCR analysis and statistical programs should
      not be the only procedure applied to verify the assay for gene expression
      assessment related to ENMs. A comparison of SYBR Green to EVA Green was
      discussed, in addition to a comparison to the latest reports regarding the
      influence of ENM thermal conductivity, surface interactions with ENMs, effects of
      ENM size and charge, as well as, the limit of detection in a qPCR assay.
      CONCLUSIONS: AuNPs have the potential to interfere with the assay mechanism of RT
      qPCR, thus, assay verification is required for AuNP-related gene expression
      studies used to evaluate toxicity. It is recommended to use HSP90 and YWHAZ as
      reference genes, i.e. these were the most stable in our study, irrespective of
      the source of the RNA, or, the point at which the AuNPs interacted with the
      assay. This report describes steps that can be utilised to generate a suitable
      method for gene expression studies associated with toxicity testing of various
      ENMs. For example, RNA standards that have been spiked with known amounts of ENMs
      should be run in conjunction with the unknown samples, in order to verify any RT
      qPCR assay and determine the degree of error.

PMID- 29017503
TI  - Effect of bacterial lipase on anaerobic co-digestion of slaughterhouse wastewater
      and grease in batch condition and continuous fixed-bed reactor.
AB  - BACKGROUND: This study aimed to investigate the effects of bacterial lipase on
      biogas production of anaerobic co-digestion of slaughterhouse wastewater (SHWW)
      and hydrolyzed grease (HG). A neutrophilic Staphylococcus xylosus strain
      exhibiting lipolytic activity was used to perform microbial hydrolysis
      pretreatment of poultry slaughterhouse lipid rich waste. RESULTS: Optimum
      proportion of hydrolyzed grease was evaluated by determining biochemical methane
      potential. A high biogas production was observed in batch containing a mixture of
      slaughterhouse composed of 75% SHWW and 25% hydrolyzed grease leading to a biogas
      yield of 0.6 L/g COD introduced. Fixed bed reactor (FBR) results confirmed that
      the proportion of 25% of hydrolyzed grease gives the optimum condition for the
      digester performance. Biogas production was significantly high until an organic
      loading rate (OLR) of 2 g COD/L. d. CONCLUSION: This study indicates that the use
      of biological pre-treatment and FBR for the co-digestion of SHWW and hydrolyzed
      grease is feasible and effective.

PMID- 29017504
TI  - Positive experiences of a vocational rehabilitation intervention for individuals
      on long-term sick leave, the Dirigo project: a qualitative study.
AB  - BACKGROUND: The process of returning to work after long-term sick leave can
      sometimes be complex. Many factors, (e.g. cooperation between different
      authorities and the individual as well as individual factors such as health,
      emotional well-being and self-efficacy) may have an impact on an individual's
      ability to work. The aim of this study was to investigate clients' experiences
      with an individually tailored vocational rehabilitation, the Dirigo project, and
      encounters with professionals working on it. The Dirigo project was based on
      collaboration between rehabilitation authorities, individually tailored
      interventions and a motivational interviewing approach. METHODS: A descriptive
      qualitative design was used with data collected through interviews. Fourteen
      individuals on long-term sick leave took part in individual semi-structured
      interviews. The interviews were analysed using content analysis. RESULTS: The
      analysis showed overall positive experience of methods and encounters with
      professionals in a vocational rehabilitation project. The positive experiences
      were based on four key factors: 1. Opportunities for receiving various dimensions
      of support. 2. Good overall treatment by the professionals. 3. Satisfaction with
      the working methods of the project, and 4. Opportunities for personal
      development. CONCLUSIONS: The main result showed that the clients had an overall
      positive experience of a vocational rehabilitation project and encounters with
      professionals who used motivational interviewing as a communication method. The
      overall positive experience indicated that their interactions with the different
      professionals may have affected their self-efficacy in general and in relation to
      transition to work. The knowledge is essential for the professionals working in
      the area of vocational rehabilitation. However, vocational rehabilitation
      interventions also need a societal approach to be able to offer clients
      opportunities for job training and real jobs.

PMID- 29017505
TI  - Study protocol: patient reported outcomes for bladder management strategies in
      spinal cord injury.
AB  - BACKGROUND: The majority of spinal cord injury (SCI) patients have urinary
      issues, such as incontinence, retention, and frequency. These problems place a
      significant burden on patients' physical health and quality of life (QoL). There
      are a wide variety of bladder management strategies available to patients with no
      clear guidelines on appropriate selection. Inappropriate bladder management can
      cause hospitalizations and serious complications, such as urosepsis and renal
      failure. Patients believe that both independence and ability to carry out daily
      activities are just as important as physical health in selecting the right
      bladder-management strategy but little is known about patient's QoL with
      different bladder managements. Our study's aim is to assess patient reported QoL
      measures with various bladder managements after SCI. This manuscript describes
      the approach, study design and common data elements for our central study.
      METHODS: This is a multi-institutional prospective cohort study comparing three
      different bladder-management strategies (clean intermittent catheterization,
      indwelling catheters, and surgery). Information collected from participants
      includes demographics, past medical and surgical history, injury characteristics,
      current and past bladder management, and SCI /bladder-related complications.
      Patient reported outcomes and QoL questionnaires were administered at enrollment
      and every 3 months for 1 year. Aims of this study protocol are: (1) to assess
      baseline QoL differences between the three different bladder-management
      strategies; (2) determine QoL impact when those using either form of catheter
      management undergo a surgery over the 1 year of follow-up among patients eligible
      for surgery; (3) assess the effects of changes in bladder management and
      complications on QoL over a 1-year longitudinal follow-up. DISCUSSION: By
      providing information about patient-reported outcomes associated with different
      bladder management strategies after SCI, and the impact of bladder management
      changes and complications on QoL, this study will provide essential information
      for shared decision-making and guide future investigation. TRIAL REGISTRATION:
      Trial registration number: www.clinicaltrials.gov : Identifier: NCT0261608; U.S.
      National Library of Medicine, wwwcf.nlm.nih.gov : Identifier: HSRP20153564.

PMID- 29017506
TI  - Mortality in patients treated with intravitreal bevacizumab for age-related
      macular degeneration.
AB  - BACKGROUND: The aim of this study is to analyze mortality in patients treated
      with bevacizumab for wet AMD. METHODS: We conducted a retrospective case-control
      study between patients who received intravitreal injections of bevacizumab as the
      sole treatment for exudative AMD between September 2008 and October 2014 (n =
      5385) and age and gender matched controls (n = 10,756). All individuals included
      in the study were reviewed for sociodemographic data and comorbidities. Survival
      analysis was performed using adjusted Cox regression, using relevant adjusted
      variables. RESULTS: During follow-up (maximum: 73 months), 1063 (19.7%)
      individuals after bevacizumab died compared with 1298 (12.1%) in the control
      group (P < .001). After adjusted Cox survival regression, mortality differed
      significantly between the groups, Odds ratio = 1.69, (95% C.I. 1.54-1.84), P <
      .001. CONCLUSIONS: We found an increased long-term mortality in individuals with
      wet AMD treated with bevacizumab compared to a same age and gender group without
      wet AMD.

PMID- 29017507
TI  - Polyunsaturated fatty acids: any role in rheumatoid arthritis?
AB  - BACKGROUND: Polyunsaturated fatty acids (PUFAs) are members of the family of
      fatty acids and are included in the diet. Particularly, western diet is usually
      low in n-3 PUFAs and high in n-6 PUFAs. PUFAs play a central role in the
      homeostasis of immune system: n-6 PUFAs have predominantly pro-inflammatory
      features, while n-3 PUFAs seem to exert anti-inflammatory and pro-resolving
      properties. Rheumatoid arthritis (RA) is a chronic inflammatory arthritis in
      which many inflammatory pathways contribute to joint and systemic inflammation,
      disease activity, and structural damage. Research on PUFAs could represent an
      important opportunity to better understand the pathogenesis and to improve the
      management of RA patients. METHODS: We searched PubMed, Embase, EBSCO-Medline,
      Cochrane Central Register of Controlled Trials (CENTRAL), CNKI and Wanfang to
      identify primary research reporting the role of n-3 PUFAs in rheumatoid arthritis
      both in humans and in animal models up to the end of March 2017. RESULTS: Data
      from animal models allows to hypothesize that n-3 PUFAs supplementation may
      represent an interesting perspective in future research as much in prevention as
      in treating RA. In humans, several case-control and prospective cohort studies
      suggest that a high content of n-3 PUFAs in the diet could have a protective role
      for incident RA in subjects at risk. Moreover, n-3 PUFAs supplementation has been
      assessed as a valuable therapeutic option also for patients with RA, particularly
      in order to improve the pain symptoms, the tender joint count, the duration of
      morning stiffness and the frequency of NSAIDs assumption. CONCLUSIONS: n-3 PUFAs
      supplementation could represent a promising therapeutic option to better control
      many features of RA. The impact of n-3 PUFAs on radiographic progression and
      synovial histopathology has not been yet evaluated, as well as their role in
      early arthritis and the combination with biologics.

PMID- 29017509
TI  - Acceptability of dietary and physical activity lifestyle modification for men
      following radiotherapy or radical prostatectomy for localised prostate cancer: a
      qualitative investigation.
AB  - BACKGROUND: The experience and acceptability of lifestyle interventions for men
      with localised prostate cancer are not well understood, yet lifestyle
      interventions are increasingly promoted for cancer survivors. We explored the
      opinions, experiences and perceived acceptability of taking part in nutritional
      and physical activity interventions amongst men with prostate cancer and their
      partners; with the ultimate plan to use such information to inform the
      development of nutritional and physical activity interventions for men with
      prostate cancer. METHODS: Semi-structured interviews with 16 men, and seven
      partners, undergoing curative surgery or radiotherapy for prostate cancer.
      Interviews explored experiences of lifestyle interventions, acceptable changes
      participants would make and perceived barriers and facilitators to change.
      Interviews were thematically analysed using the framework approach. RESULTS: Men
      were frequently open to lifestyle modification and family support was considered
      vital to facilitate change. Health beneficial, clinician endorsed,
      understandable, enjoyable interventions were perceived as attractive. Barriers
      included 'modern' digital technology, poor weather, competing commitments or
      physical limitations, most notably incontinence following radical prostatectomy.
      Men were keen to participate in research, with few negative aspects identified.
      CONCLUSIONS: Men are willing to change behaviour but this needs to be supported
      by clinicians and health professionals facilitating lifestyle change. An
      'intention-behaviour gap', when an intended behaviour does not materialise, may
      exist. Digital technology for data collection and lifestyle measurement may not
      be suitable for all, and post-surgery urinary incontinence is a barrier to
      physical activity. These novel findings should be incorporated into lifestyle
      intervention development, and implemented clinically.

PMID- 29017508
TI  - On neuromechanical approaches for the study of biological and robotic grasp and
      manipulation.
AB  - Biological and robotic grasp and manipulation are undeniably similar at the level
      of mechanical task performance. However, their underlying fundamental biological
      vs. engineering mechanisms are, by definition, dramatically different and can
      even be antithetical. Even our approach to each is diametrically opposite:
      inductive science for the study of biological systems vs. engineering synthesis
      for the design and construction of robotic systems. The past 20 years have seen
      several conceptual advances in both fields and the quest to unify them. Chief
      among them is the reluctant recognition that their underlying fundamental
      mechanisms may actually share limited common ground, while exhibiting many
      fundamental differences. This recognition is particularly liberating because it
      allows us to resolve and move beyond multiple paradoxes and contradictions that
      arose from the initial reasonable assumption of a large common ground. Here, we
      begin by introducing the perspective of neuromechanics, which emphasizes that
      real-world behavior emerges from the intimate interactions among the physical
      structure of the system, the mechanical requirements of a task, the feasible
      neural control actions to produce it, and the ability of the neuromuscular system
      to adapt through interactions with the environment. This allows us to articulate
      a succinct overview of a few salient conceptual paradoxes and contradictions
      regarding under-determined vs. over-determined mechanics, under- vs. over
      actuated control, prescribed vs. emergent function, learning vs. implementation
      vs. adaptation, prescriptive vs. descriptive synergies, and optimal vs. habitual
      performance. We conclude by presenting open questions and suggesting directions
      for future research. We hope this frank and open-minded assessment of the state
      of-the-art will encourage and guide these communities to continue to interact and
      make progress in these important areas at the interface of neuromechanics,
      neuroscience, rehabilitation and robotics.

PMID- 29017510
TI  - Synthesis of europium-doped VSOP, customized enhancer solution and improved
      microscopy fluorescence methodology for unambiguous histological detection.
AB  - BACKGROUND: Intrinsic iron in biological tissues frequently precludes unambiguous
      the identification of iron oxide nanoparticles when iron-based detection methods
      are used. Here we report the full methodology for synthesizing very small iron
      oxide nanoparticles (VSOP) doped with europium (Eu) in their iron oxide core (Eu
      VSOP) and their unambiguous qualitative and quantitative detection by
      fluorescence. METHODS AND RESULTS: The resulting Eu-VSOP contained 0.7 to 2.7% Eu
      relative to iron, which was sufficient for fluorescent detection while not
      altering other important particle parameters such as size, surface charge, or
      relaxivity. A customized enhancer solution with high buffer capacity and nearly
      neutral pH was developed to provide an antenna system that allowed fluorescent
      detection of Eu-VSOP in cells and histologic tissue slices as well as in
      solutions even under acidic conditions as frequently obtained from dissolved
      organic material. This enhancer solution allowed detection of Eu-VSOP using a
      standard fluorescence spectrophotometer and a fluorescence microscope equipped
      with a custom filter set with an excitation wavelength (lambdaex) of 338 nm and
      an emission wavelength (lambdaem) of 616 nm. CONCLUSION: The fluorescent
      detection of Eu-doped very small iron oxide nanoparticles (Eu-VSOP) provides a
      straightforward tool to unambiguously characterize VSOP biodistribution and
      toxicology at tissue, and cellular levels, providing a sensitive analytical tool
      to detect Eu-doped IONP in dissolved organ tissue and biological fluids with
      fluorescence instruments.

PMID- 29017511
TI  - Mechanical wrist traction as a non-invasive treatment for carpal tunnel syndrome:
      a randomized controlled trial.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is a common, compressive nerve
      entrapment disorder with symptoms of numbness, paresthesia, and pain. Carpal
      tunnel release surgery is the only known long-term effective treatment. However,
      surgery is invasive and up to 30% of patients report recurrence or persistence of
      symptoms or suffer from post-surgical complications. A promising non-surgical
      treatment for CTS is mechanical wrist traction. The purpose of this study was to
      evaluate clinical outcomes following mechanical traction in patients with CTS
      compared to care as usual. METHODS: Adult patients (N = 181, mean age 58.1 (13.0)
      years, 67% women) with electrodiagnostically confirmed CTS were recruited from an
      outpatient neurology clinic in the Netherlands between October 2013 and April
      2015. After baseline assessments, patients were randomized to either the
      intervention group (12 treatments with mechanical traction, twice a week for a
      period of 6 weeks) or "care as usual". The main clinical outcome measure was
      surgery during 6 months' follow-up. In addition, symptom severity was measured
      using the Boston Carpal Tunnel Questionnaire (BCTQ) at baseline, 3, and 6 months'
      follow-up. Baseline characteristics and severity of CTS symptoms at follow-up
      were compared between the intervention and care-as-usual groups using a t test
      and chi 2 tests. Time to event (surgery) between the groups was analyzed using
      Kaplan-Meier survival analysis and Cox proportional hazards analysis. RESULTS:
      The intervention group had fewer surgeries (28%) compared to the care-as-usual
      group (43%) during follow-up (chi21 = 4.40, p = .036). Analyses of the survival
      curves revealed a statistically significant difference between the groups over
      time (log-rank test chi 21 = 6.94, p = .008). At 6 months' follow-up, symptom
      severity and functional status scores had significantly decreased from baseline
      in both groups (p < .001) and the improvements did not differ between the two
      groups. CONCLUSIONS: Mechanical traction is associated with fewer surgical
      interventions compared to care as usual in CTS patients. Reductions in patient
      reported symptoms at 6 months' follow-up was similar in both groups. The long
      term effects of mechanical traction require further evaluation. TRIAL
      REGISTRATION: ClinicalTrials.gov, ID: NL44692.008.13 . Registered on 19 September
      2013.

PMID- 29017513
TI  - Association between TNF, IL1B, IL6, IL10 and IFNG polymorphisms and recurrent
      miscarriage: a case control study.
AB  - BACKGROUND: Approximately half of recurrent miscarriages have unexplained
      etiology. Recent evidences suggest that cytokines are important determinants in
      pregnancy maintenance and as such, cytokine gene polymorphisms, which can affect
      cytokine production and/or functionality, could play a role in the disorder.
      Thus, we aimed to investigate the association of selected cytokine gene
      polymorphisms with risk of recurrent miscarriage among Chinese. METHODS: TNF 
      238G > A, TNF -308G > A, IL1B -511 T > C, IL1B 3954C > T, IL6 -174G > C, IL6 
      634C > G, IL10 -1082A > G and IFNG 874A > T polymorphisms were genotyped on 775
      women with idiopathic recurrent miscarriage and 805 healthy parous control women.
      Logistic regression analysis was performed to determine the odds ratios (ORs) of
      the association between the polymorphisms and recurrent miscarriage risk.
      RESULTS: Among the eight polymorphisms studied, only the IL1B -511 T > C and IL6 
      634C > G polymorphisms showed statistically significant associations with
      recurrent miscarriage risk. For the former, a significantly increased risk of
      recurrent miscarriage was observed for the mutant (CC) genotype (OR: 1.377; 95%
      CI: 1.039-1.824; P = 0.026). However, for the IL6 -634C > G polymorphism, a
      decreased recurrent miscarriage risk was observed for the heterozygous (CG)
      genotype (OR: 0.614; 95% CI: 0.493-0.765; P < 0.001) and the mutant (GG) genotype
      (OR: 0.414; 95% CI: 0.251-0.684; P = 0.001). CONCLUSIONS: The IL1B -511 T > C
      polymorphism may serve as important risk factor for recurrent miscarriage while
      the IL6 -634C > G polymorphism may protect against the risk of recurrent
      miscarriage.

PMID- 29017512
TI  - Metastatic pathway and the microvascular and physicochemical microenvironments of
      human melanoma xenografts.
AB  - BACKGROUND: Malignant melanoma of the skin can metastasize through blood vessels
      and lymphatics. The primary tumor develops a vascular microenvironment
      characterized by abnormal blood vessels and lymphatics and a physicochemical
      microenvironment characterized by low oxygen tension, regions with hypoxic
      tissue, and high interstitial fluid pressure (IFP). This study aimed at
      identifying relationships between the metastatic route of melanomas and
      characteristic features of the microvascular and physicochemical
      microenvironments of the primary tumor. METHODS: Two patient-derived xenograft
      (PDX) models (E-13, N-15) and four cell line-derived xenografts (CDX) models (C
      10, D-12, R-18, T-22) of human melanoma were included in the study. Tumors were
      transplanted to an orthotopic site in BALB/c-nu/nu mice, and when the tumors had
      grown to a volume of 500-600 mm3, the IFP of the primary tumor was measured and
      the hypoxia marker pimonidazole was administered before the host mouse was
      euthanized. The primary tumor, lungs, and six pairs of lymph nodes were evaluated
      by examining hematoxylin/eosin-stained and immunostained histological
      preparations. The expression of angiogenesis-related genes was assessed by
      quantitative PCR. RESULTS: C-10, D-12, and E-13 tumors disseminated primarily by
      the hematogenous route and developed pulmonary metastases. These tumors showed
      high angiogenic activity and high expression of the F3 gene as well as ANGPT2 and
      TIE1, genes encoding proteins of the angiopoietin-tie system. N-15, R-18, and T
      22 tumors disseminated mainly by the lymphogenous route and developed metastases
      in draining lymph nodes. These tumors had highly elevated IFP and showed high
      expression of NRP2, a gene encoding neuropilin-2. CONCLUSION: The primary
      metastatic route of orthotopic human melanoma xenografts and the development of
      lung and lymph node metastases are influenced significantly by the microvascular
      and physicochemical microenvironments of the primary tumor.

PMID- 29017515
TI  - Low recurrence rate of anchored conjunctival rotation flap technique in pterygium
      surgery.
AB  - BACKGROUND: To report the recurrence rate for an anchored conjunctival rotation
      flap technique in primary pterygium surgery. METHODS: Primary pterygium surgeries
      performed using anchored conjunctival rotation flap techniques (110 eyes in 110
      patients) with a minimum follow-up of 12 months were reviewed. In this technique,
      a conjunctival flap is rotated to cover the bare sclera and suture-fixated with
      either 8-0 polyglactin (41 eyes) or 10-0 nylon (69 eyes). The recurrence rate was
      determined, and the two suture materials utilized were compared. RESULTS: The
      recurrence rate was 2.71% (3 cases in 110 eyes) when an anchored conjunctival
      rotation flap technique was used and patients were monitored for 26.40 +/- 17.09
      months. Interestingly, the recurrences were only observed in polyglactin-sutured
      eyes. No recurrence was detected in nylon-sutured eyes. No other complications
      were observed in either group. CONCLUSIONS: The anchored conjunctival rotation
      flap technique for pterygium surgery has a relatively low recurrence rate. Nylon
      suture-fixation of the flap was found to be superior to polyglactin suture
      fixation in preventing recurrence.

PMID- 29017514
TI  - Impact of type 2 diabetes mellitus on in-hospital-mortality after major
      cardiovascular events in Spain (2002-2014).
AB  - BACKGROUND: Diabetes mellitus has long been associated with cardiovascular
      events. Nevertheless, the higher burden of traditional cardiovascular risk
      factors reported in high-income countries is offset by a more widespread use of
      preventive measures and revascularization or other invasive procedures. The aim
      of this investigation is to describe trends in number of cases and outcomes, in
      hospital mortality (IHM) and length of hospital stay (LHS), of hospital
      admissions for major cardiovascular events between type 2 diabetes (T2DM) and
      matched non-diabetes patients. METHODS: Retrospective study using National
      Hospital Discharge Database, analyzed in 4 years 2002, 2006, 2010, 2014, in
      Spain. We included patients (>= 40 years old) with a primary diagnosis of
      myocardial infarction, ischemic and hemorrhagic stroke, aortic aneurysm and
      dissection and acute lower limb ischemia in people with T2DM. Cases were matched
      with controls (without T2DM) by ICD-9-CM codes, sex, age, province of residence
      and year. RESULTS: We selected 130,011 matched couples (50,427 with myocardial
      infarction, 60,236 with stroke, 2599 with aortic aneurysm and dissection and
      16,749 with acute lower limb ischemia. Among T2DM patients we found increasing
      numbers of admissions overtime for stroke (10,794 in 2002 vs 17,559 in 2014),
      aortic aneurysm and dissection (390 vs 841) and acute lower limb ischemia (3854
      vs. 4548). People were progressively older (except for myocardial infarction),
      had more comorbidities (especially T2DM patients), and were more frequently coded
      overtime for cardiovascular risk factors (smoking, obesity, hypertension, lipid
      disorders) and renal diseases. LHS and IHM declined overtime, though IHM only did
      it significantly in T2DM patients. Multivariable adjustment showed that T2DM
      patients had a significantly 15% higher mortality rate during admission for
      myocardial infarction, a 6% higher mortality for stroke, and a 6% higher
      mortality rate for "all cardiovascular events combined", than non-diabetic
      matched controls. CONCLUSIONS: The number of hospital admissions for stroke,
      aortic aneurysm and dissection and acute lower limb ischemia increased overtime,
      but remained stable for myocardial infarction. T2DM is associated to higher IHM
      after major cardiovascular events. Further research is needed to help us
      understand the reasons for an apparently increased mortality in T2DM patients
      when admitted to hospital for some major cardiovascular events.

PMID- 29017517
TI  - Traumatic penile amputation: a case report.
AB  - BACKGROUND: Traumatic amputation of the penis is a rare surgical emergency.
      Although repair techniques have been well described in literature, failure of
      replantation and its causes are poorly understood and reported. Herein, we report
      the case of a 9 year old boy who underwent replantation of his amputated penis
      with delayed failure of the surgery, along with a discussion of recent advances
      in the management of this condition. CASE  PRESENTATION: A 9-year-old boy was
      referred to our hospital for traumatic amputation of the penis. Papaverine aided
      microsurgical replantation of the severed part was performed, but by 48 h, the
      glans became discoloured and necrosis set in by 4 days. Unfortunately, by day 12
      two thirds of the re-implanted penis was lost along with overlying skin.
      CONCLUSION: Replantation of an amputated penis in a pediatric patient is a
      daunting task even for experienced surgeons. The vasodilatory effect of
      papaverine for vascular anastomosis is well described, but the use of a
      paediatric cannula for identification and instillation of papaverine into penile
      vasculature, has not been described for the repair of penile amputation. Despite
      its apparent failure, we believe this technique may be valuable to surgeons who
      might encounter this rare event in their surgical practice, especially in
      resource limited settings like ours.

PMID- 29017516
TI  - Identification of a RAC/AKT-like gene in Leishmania parasites as a putative
      therapeutic target in leishmaniasis.
AB  - BACKGROUND: Leishmaniasis is one of the world's most neglected diseases caused by
      at least 20 different species of the protozoan parasite Leishmania. Although new
      drugs have become recently available, current therapy for leishmaniasis is still
      unsatisfactory. A subgroup of serine/threonine protein kinases named as related
      to A and C protein kinases (RAC), or protein kinase B (PKB)/AKT, has been
      identified in several organisms including Trypanosoma cruzi parasites. PKB/AKT
      plays a critical role in mammalian cell signaling promoting cell survival and is
      a major drug target in cancer therapy. However, the role of protozoan parasitic
      PKB/AKT remains to be elucidated. RESULTS: We have found that anti-human AKT
      antibodies recognized a protein of about 57 kDa in Leishmania spp. parasites.
      Anti-human phospho-AKT(Thr308) antibodies identified a protein in extracts from
      Leishmania spp. that was upregulated following parasite exposure to stressful
      conditions, such as nutrient deprivation or heat shock. Incubation of AKT
      inhibitor X with Leishmania spp. promastigotes under stressful conditions or with
      Leishmania-infected macrophages led to parasite cell death. We have identified
      and cloned a novel gene from Leishmania donovani named Ld-RAC/AKT-like gene,
      encoding a 510-amino acid protein of approximately 57.6 kDa that shows a 26.5%
      identity with mammalian AKT1. Ld-RAC/AKT-like protein contains major mammalian
      PKB/AKT hallmarks, including the typical pleckstrin, protein kinase and AGC
      kinase domains. Unlike mammalian AKT that contains key phosphorylation sites at
      Thr308 and Ser473 in the activation loop and hydrophobic motif, respectively, Ld
      RAC/AKT-like protein has a Thr residue in both motifs. By domain sequence
      comparison, we classified AKT proteins from different origins in four major
      subcategories that included different parasites. CONCLUSIONS: Our data suggest
      that Ld-RAC/AKT-like protein represents a Leishmania orthologue of mammalian AKT
      involved in parasite stress response and survival, and therefore could become a
      novel therapeutic and druggable target in leishmaniasis therapy. In addition,
      following comparative sequence analyses, we found the RAC/AKT-like proteins from
      Leishmania constitute a subgroup by themselves within a general AKT-like protein
      family.

PMID- 29017518
TI  - Current practice in methodology and reporting of the sample size calculation in
      randomised trials of hip and knee osteoarthritis: a protocol for a systematic
      review.
AB  - BACKGROUND: A key aspect of the design of randomised controlled trials (RCTs) is
      determining the sample size. It is important that the trial sample size is
      appropriately calculated. The required sample size will differ by clinical area,
      for instance, due to the prevalence of the condition and the choice of primary
      outcome. Additionally, it will depend upon the choice of target difference
      assumed in the calculation. Focussing upon the hip and knee osteoarthritis
      population, this study aims to systematically review how the trial size was
      determined for trials of osteoarthritis, on what basis, and how well these
      aspects are reported. METHODS: Several electronic databases (Medline, Cochrane
      library, CINAHL, EMBASE, PsycINFO, PEDro and AMED) will be searched to identify
      articles on RCTs of hip and knee osteoarthritis published in 2016. Articles will
      be screened for eligibility and data extracted independently by two reviewers.
      Data will be extracted on study characteristics (design, population, intervention
      and control treatments), primary outcome, chosen sample size and justification,
      parameters used to calculate the sample size (including treatment effect in
      control arm, level of variability in primary outcome, loss to follow-up rates).
      Data will be summarised across the studies using appropriate summary statistics
      (e.g. n and %, median and interquartile range). The proportion of studies which
      report each key component of the sample size calculation will be presented. The
      reproducibility of the sample size calculation will be tested. DISCUSSION: The
      findings of this systematic review will summarise the current practice for sample
      size calculation in trials of hip and knee osteoarthritis. It will also provide
      evidence on the completeness of the reporting of the sample size calculation,
      reproducibility of the chosen sample size and the basis for the values used in
      the calculation. TRIAL REGISTRATION: As this review was not eligible to be
      registered on PROSPERO, the summary information was uploaded to Figshare to make
      it publicly accessible in order to avoid unnecessary duplication amongst other
      benefits ( https://doi.org/10.6084/m9.figshare.5009027.v1) ; Registered January
      17, 2017.

PMID- 29017519
TI  - Development of an infant feeding core outcome set for childhood obesity
      interventions: study protocol.
AB  - BACKGROUND: Childhood obesity is a significant public health challenge that
      affects approximately one in five children worldwide. Infant feeding practices
      are implicated in the aetiology of childhood obesity. Infant feeding
      interventions for childhood obesity are increasingly popular but outcome
      reporting is inconsistent across trials. Lack of standardisation limits
      examination of intervention effects and mechanisms of change. The aim of the
      current project is to develop a core set of infant feeding outcomes for children
      <= 1 year old, to be evaluated in childhood obesity intervention trials. METHODS:
      This project will use similar methodology to previous core outcome development
      research. An infant feeding core outcome set (COS) will be developed in four
      stages: (1) a systematic review of the literature, (2) discussion and
      clarification of outcomes in a meeting involving multiple stakeholder
      perspectives, (3) prioritisation of outcomes using the Delphi technique with an
      expert panel of stakeholders, and (4) achieving consensus on the COS using the
      nominal group technique (NGT) consensus meeting. An online Delphi survey will be
      conducted following the NGT meeting to prioritise outcomes identified in the
      systematic review. An NGT meeting will be conducted with groups of health
      professionals, non-clinician researchers, and parents of infants <= 1 year old,
      to achieve final consensus on the infant feeding COS. DISCUSSION: This study aims
      to develop a core outcome set of infant feeding outcomes for randomised infant
      feeding studies to prevent childhood obesity. This research will improve
      examination and syntheses of the outcomes of such studies to prevent and reduce
      childhood obesity.

PMID- 29017521
TI  - An integrative review of e-learning in the delivery of self-management support
      training for health professionals.
AB  - BACKGROUND: E-learning involves delivery of education through Information and
      Communication Technology (ITC) using a wide variety of instructional designs,
      including synchronous and asynchronous formats. It can be as effective as face-to
      face training for many aspects of health professional training. There are,
      however, particular practices and skills needed in providing patient self
      management support, such as partnering with patients in goal-setting, which may
      challenge conventional practice norms. E-learning for the delivery of self
      management support (SMS) continuing education to existing health professionals is
      a relatively new and growing area with limited studies identifying features
      associated with best acquisition of skills in self-management support. METHODS:
      An integrative literature review examined what is known about e-learning for self
      management support. This review included both qualitative and quantitative
      studies that focused on e-learning provided to existing health professionals for
      their continuing professional development. Papers were limited to those published
      in English between 2006 and 2016. Content analysis was used to organize and focus
      and describe the findings. RESULTS: The search returned 1505 articles, with most
      subsequently excluded based on their title or abstract. Fifty-two full text
      articles were obtained and checked, with 42 excluded because they did not meet
      the full criteria. Ten peer-reviewed articles were included in this review. Seven
      main themes emerged from the content analysis: participants and professions;
      time; package content; guiding theoretical framework; outcome measures; learning
      features or formats; and learning barriers. These themes revealed substantial
      heterogeneity in instructional design and other elements of e-learning applied to
      SMS, indicating that there is still much to understand about how best to deliver
      e-learning for SMS skills development. CONCLUSIONS: Few e-learning approaches
      meet the need for high levels of interactivity, reflection, practice and
      application to practice for health professionals learning to deliver effective
      SMS. Findings suggest that the context of SMS for patients with chronic condition
      matters to how health professional training is delivered, to ensure partnership
      and person-centred care. Further creative approaches and their rigorous
      evaluation are needed to deliver completely online learning in this space.
      Blended learning that combines e-learning and face-to-face methods is suggested
      to support SMS skills development for health professionals.

PMID- 29017522
TI  - Analysis of plasma multiplex cytokines and increased level of IL-10 and IL-1Ra
      cytokines in febrile seizures.
AB  - BACKGROUND: Febrile seizures are the most common form of childhood seizures.
      Fever generation involves many cytokines, including both pro- and anti
      inflammatory cytokines. Some of these cytokines also induce febrile seizures. We
      compared cytokine production in children with a fever alone (healthy control
      group) and febrile seizure children group. Also, we evaluated the cytokine level
      of children with a fever alone and febrile seizure history. METHODS: Fifty
      febrile seizure patients and 39 normal control patients who visited the emergency
      department of Konkuk University Hospital from December 2015 to December 2016 were
      included in this study. Blood was taken from the peripheral vessels of children
      in all groups within 1 h of the seizure, and serum was obtained immediately.
      Serum samples from patients with only a fever and a febrile seizure history (N =
      13) and afebrile seizure controls (N = 12) were also analyzed. RESULTS: The serum
      IL-10 and IL-1Ra levels were significantly higher in the febrile seizure patients
      than in the fever-only control, fever only with a febrile seizure history, and
      afebrile seizure groups (p < 0.05). The serum IFN-gamma and IL-6 levels were
      significantly higher in the febrile seizure patients than in the afebrile seizure
      group (p < 0.05). The serum IL-8 levels were higher in the febrile seizure
      patients than in the fever only controls (p < 0.05). CONCLUSIONS: The serum
      levels of the IFN-gamma, IL-6, and IL-8 pro-inflammatory cytokines and the serum
      levels of the IL-10 and IL-1Ra anti-inflammatory cytokines were significantly
      higher in the febrile seizure children. Furthermore, the serum level of IL-1Ra
      was more increased in the febrile seizure group than in the same patients with
      only a fever. Our data suggest that increased serum IL-10 and IL-1Ra may play
      potential roles as anti-inflammatory cytokines in a compensation mechanism that
      shortens the seizure duration or prevents a febrile seizure attack. Therefore,
      anti-inflammatory cytokines, including IL-10 and IL-1Ra, have potential as
      therapeutic targets for the prevention of seizures and nervous system development
      of children.

PMID- 29017520
TI  - The nuclear receptor ERbeta engages AGO2 in regulation of gene transcription, RNA
      splicing and RISC loading.
AB  - BACKGROUND: The RNA-binding protein Argonaute 2 (AGO2) is a key effector of RNA
      silencing pathways It exerts a pivotal role in microRNA maturation and activity
      and can modulate chromatin remodeling, transcriptional gene regulation and RNA
      splicing. Estrogen receptor beta (ERbeta) is endowed with oncosuppressive
      activities, antagonizing hormone-induced carcinogenesis and inhibiting growth and
      oncogenic functions in luminal-like breast cancers (BCs), where its expression
      correlates with a better prognosis of the disease. RESULTS: Applying interaction
      proteomics coupled to mass spectrometry to characterize nuclear factors
      cooperating with ERbeta in gene regulation, we identify AGO2 as a novel partner
      of ERbeta in human BC cells. ERbeta-AGO2 association was confirmed in vitro and
      in vivo in both the nucleus and cytoplasm and is shown to be RNA-mediated. ChIP
      Seq demonstrates AGO2 association with a large number of ERbeta binding sites,
      and total and nascent RNA-Seq in ERbeta + vs ERbeta - cells, and before and after
      AGO2 knock-down in ERbeta + cells, reveals a widespread involvement of this
      factor in ERbeta-mediated regulation of gene transcription rate and RNA splicing.
      Moreover, isolation and sequencing by RIP-Seq of ERbeta-associated long and small
      RNAs in the cytoplasm suggests involvement of the nuclear receptor in RISC
      loading, indicating that it may also be able to directly control mRNA translation
      efficiency and stability. CONCLUSIONS: These results demonstrate that AGO2 can
      act as a pleiotropic functional partner of ERbeta, indicating that both factors
      are endowed with multiple roles in the control of key cellular functions.

PMID- 29017523
TI  - Single tooth torque correction in the lower frontal area by a completely
      customized lingual appliance.
AB  - BACKGROUND: Aim of this study was to analyze the efficacy and precision of the
      completely customized lingual appliance (CCLA) regarding the single tooth torque
      correction. The study also examined external apical root resorptions as possible
      side effects of torque correction and the changings of the periodontal situation.
      METHODS: A case series of three patients were included. The patients showed a
      single tooth torque problem with a gingival recession and were treated with the
      CCLA. Plaster casts before and after treatment and plaster casts of the set up
      were scanned and superimposed. Deviations between the two plaster casts were
      analyzed at different points of interest. Changes of the gingival recession were
      compared before and after treatment. Relative root resorptions were measured by
      the orthopantomograms. Treatment times were assessed by the records of the
      patients. Results were presented descriptively. RESULTS: The mean change of the
      most apical part of the root reached by the orthodontic treatment was 1.8 +/- 0.3
      mm. The largest deviation between set up and final model was measured on the
      occlusal surface of the tooth 36 with 0.8 mm. Most measurement points showed a
      deviation of 0.5 mm or less. The depths of the gingival recession showed a
      significant reduction of 4.7 mm. The widths of the gingival recession were
      reduced by 1.1 mm. The average relative root resorption of the corrected teeth
      was 2.7 +/- 1.5%. The average treatment time was 13.8 +/- 4.5 months.
      CONCLUSIONS: This is the first study showing that the CCLA with its high
      precision is very effective in correcting single tooth torque problems.
      Orthodontic torque correction resulted in a significant reduction of gingival
      recessions and caused only negligible root resorptions.

PMID- 29017524
TI  - Chronic obstructive pulmonary disease, bronchial asthma and allergic rhinitis in
      the adult population within the commonwealth of independent states: rationale and
      design of the CORE study.
AB  - BACKGROUND: Main treatable Chronic Respiratory Diseases (CRDs) like Chronic
      Obstructive Pulmonary Disease (COPD), Bronchial Asthma (BA) and Allergic Rhinitis
      (AR) are underdiagnosed and undertreated worldwide. CORE study was aimed to
      assess the point prevalence of COPD, BA and AR in the adult population of major
      cities of Commonwealth of Independent States (CIS) countries - Azerbaijan,
      Kazakhstan, and Ukraine based on study questionnaires and/or spirometry, and to
      document risk factors, characterize the COPD, BA and AR population to provide a
      clearer "epidemiological data". METHODS: A descriptive, cross-sectional,
      population-based epidemiological study conducted from 2013 to 2015 with two-stage
      cluster geographical randomization. Interviewers conducted face-to-face visits at
      respondent's household after informed consent and eligibility assessment
      including interviews, anthropometry, spirometry (with bronchodilator test) and
      completion of disease-specific questionnaires. RESULTS: Two thousand eight
      hundred forty-two respondents (Ukraine: 964 from Ukraine; 945 from Kazakhstan;
      933 Azerbaijan) were enrolled. Mean age was 40-42 years and males were 37%-42%
      across three countries. In Kazakhstan 62.8% were Asians, but in Ukraine and in
      Azerbaijan 99.7% and 100.0%, respectively, were Caucasians. Manual labourers
      constituted 40.5% in Ukraine, 22.8% in Kazakhstan and 22.0% in Azerbaijan, while
      office workers were 16.1%, 31.6% and 36.8% respectively. 51.3% respondents in
      Ukraine, 64.9% in Kazakhstan and 69.7% in Azerbaijan were married. CONCLUSION:
      CORE study collected information that can be supportive for health policy
      decision makers in allocating healthcare resources in order to improve diagnosis
      and management of CRDs. The detailed findings will be described in future
      publications. TRIAL REGISTRATION: Study Protocol Summary is disclosed at
      GlaxoSmithKline Clinical Study Register on Jun 06, 2013, study ID 116757 .

PMID- 29017525
TI  - Is vegetarian diet associated with a lower risk of breast cancer in Taiwanese
      women?
AB  - BACKGROUND: Studies on the relationship between vegetarian diet and breast cancer
      in Asian populations are limited. This study aimed to investigate the
      relationship between vegetarian diet, dietary patterns, and breast cancer in
      Taiwanese women. METHODS: This case-control study compared the dietary patterns
      of 233 breast cancer patients and 236 age-matched controls. A questionnaire about
      vegetarian diets and 28 frequently-consumed food items was administered to these
      469 patients in the surgical department of Taipei Tzu Chi Hospital. Serum
      biochemical status was also examined. RESULTS: There were no significant
      differences between the two groups for age, education, family history, oral
      contraceptive usage, or regular exercise. However, the cancer group presented
      with both a higher body mass index and an older age of primiparity (P < 0.05).
      Two food items (shellfish and seafood) were highly correlated (correlation
      coefficient = 0.77), so shellfish was excluded to avoid multicollinearity. A
      factor analysis of 27 food items produced five dietary patterns: meat, processed
      meat, fruit/vegetable/soybean, dessert/sugar, and fermented food. Multivariate
      logistic regression showed that meat/fat and processed meat dietary patterns were
      associated with breast cancer risk (odds ratio (OR): 2.22, 95% CI 1.67-2.94, P <
      0.001; OR: 1.49, 95% CI 1.09-2.04, P = 0.013, respectively). Vegetarian diet,
      high isoflavone intake, and high albumin levels were inversely associated with
      breast cancer risk (P < 0.05). Vegetarians had a higher daily soy isoflavone
      intake than non-vegetarians (25.9 +/- 25.6 mg vs. 18.1 +/- 15.6 mg, P < 0.001).
      CONCLUSIONS: Vegetarian diets show as protective role against breast cancer risk,
      while meat and processed meat dietary patterns are associated with a higher
      breast cancer risk.

PMID- 29017526
TI  - Tuberculosis knowledge, attitudes and practices of patients at primary health
      care facilities in a South African metropolitan: research towards improved health
      education.
AB  - BACKGROUND: Health education is important to empower patients and encourage their
      contribution towards tuberculosis (TB) control. In South Africa, health education
      activities are integrated into services provided at the primary health care (PHC)
      level. This study was conducted in a high TB burden metropolitan area in South
      Africa. The objective was to assess TB-related knowledge, attitudes and infection
      control practices of patients attending PHC facilities. METHODS: In September and
      October 2015, a cross-sectional survey using fieldworker-administered
      questionnaires was conducted among patients older than 17 years attending 40 PHC
      facilities in the Mangaung Metropolitan. Convenience sampling was used to select
      patients. Participation in the study was voluntary. Descriptive, inferential and
      multivariate logistic regression analyses were performed. Statistical
      significance was considered at alpha <0.05 and 95% confidence interval. RESULTS:
      A total of 507 patients' data were included in the analysis. Most of the patients
      knew that TB transmission is facilitated by crowded conditions (84.6%) and that
      pulmonary TB is contagious (73.0%). Surprisingly, the majority of patients also
      believed that one can get TB from sharing toothbrushes (85.0%) or kissing
      (65.0%). An overwhelming majority of patients perceived TB to be serious (89.7%),
      and concurred that taking treatment (97.2%) and opening windows to prevent
      transmission in PHC facilities (97.0%) are important. Being employed (AOR: 11.5;
      CI: 4.8-27.6), having received TB infection control information from a PHC
      facility (AOR: 2.2; CI: 1.5-3.4), and being a TB patient (AOR: 1.6; CI: 1.02
      2.46) increased the likelihood of adopting good infection control practices.
      CONCLUSION: These findings highlight the need for health education efforts to
      strengthen accurate information dissemination to promote sound TB knowledge and
      attitudes among patients attending PHC facilities. Health education efforts
      should also capitalise on the positive finding of this study that information
      dissemination at PHC facilities increases good infection control practices.

PMID- 29017527
TI  - Potential return on investment of a family-centered early childhood intervention:
      a cost-effectiveness analysis.
AB  - BACKGROUND: ParentCorps is a family-centered enhancement to pre-kindergarten
      programming in elementary schools and early education centers. When implemented
      in high-poverty, urban elementary schools serving primarily Black and Latino
      children, it has been found to yield benefits in childhood across domains of
      academic achievement, behavior problems, and obesity. However, its long-term cost
      effectiveness is unknown. METHODS: We determined the cost-effectiveness of
      ParentCorps in high-poverty, urban schools using a Markov Model projecting the
      long-term impact of ParentCorps compared to standard pre-kindergarten
      programming. We measured costs and quality adjusted life years (QALYs) resulting
      from the development of three disease states (i.e., drug abuse, obesity, and
      diabetes); from the health sequelae of these disease states; from graduation from
      high school; from interaction with the judiciary system; and opportunity costs of
      unemployment with a lifetime time horizon. The model was built, and analyses were
      performed in 2015-2016. RESULTS: ParentCorps was estimated to save $4387 per
      individual and increase each individual's quality adjusted life expectancy by
      0.27 QALYs. These benefits were primarily due to the impact of ParentCorps on
      childhood obesity and the subsequent predicted prevention of diabetes, and
      ParentCorps' impact on childhood behavior problems and the subsequent predicted
      prevention of interaction with the judiciary system and unemployment. Results
      were robust on sensitivity analyses, with ParentCorps remaining cost saving and
      health generating under nearly all assumptions, except when schools had very
      small pre-kindergarten programs. CONCLUSIONS: Effective family-centered
      interventions early in life such as ParentCorps that impact academic, behavioral
      and health outcomes among children attending high-poverty, urban schools have the
      potential to result in longer-term health benefits and substantial cost savings.

PMID- 29017528
TI  - First case of Mycobacterium marseillense lymphadenitis in a child.
AB  - BACKGROUND: Nontuberculous mycobacteria (NTM) are pathogens that commonly affect
      the paediatric population and its most frequent manifestation is a cervicofacial
      lymphadenopathy. With the improvement of technologies, new species have been
      recently identified. CASE PRESENTATION: We report the first case of NMT
      lymphadenitis in a child caused by Mycobacterium marseillense, a newly described
      species belonging to Mycobacterium avium complex. CONCLUSIONS: Improving the
      identification of these newly discovered mycobacteria, further information will
      be available about their clinical involvement and their best treatment.

PMID- 29017529
TI  - Short review on human umbilical cord lining epithelial cells and their potential
      clinical applications.
AB  - BACKGROUND: The human umbilical cord has been studied extensively in the past two
      decades. It is free of ethical dilemmas, non-tumorigenic, and less immunogenic
      and thus provides a significant advantage over other stem cell sources. The cord
      lining yields both mesenchymal and epithelial stem cells. The mesenchymal cells
      have been appraised at length by many researchers, which led to the current
      review focusing on the cord lining epithelial cells (CLECs). These cells have
      high proliferative capacity and their superior harvest and multiplication, using
      the revolutionary CellOptimaTM technology, makes them better candidates in
      comparison to contemporary adult stem cells. Following 30 replication cycles
      these cells have been observed to retain their stemness, with their phenotype and
      karyotype intact. However, their remarkable immunosuppressant properties,
      protecting self as well as co-transplanted allografts from rejection, are what
      truly define their transplantation potential. They have been successfully applied
      to many chronic conditions, using animal models, including type 1 diabetes,
      limbal stem cell deficiency, burn injuries, and wound healing, etc. with
      encouraging results. CONCLUSIONS: This review first discusses some of the
      advantages afforded by CLECs over other stem cell lines and then delineates their
      potential use in various clinical applications. Clinical trials using CLECs are
      currently underway in the US in collaboration with CellResearch Corp. and their
      potential positive findings will help garner an FDA approval, likely leading to
      the eventual commercialization of this promising technology.

PMID- 29017530
TI  - Customized microscale approach for optimizing two-phase bio-oxidations of alkanes
      with high reproducibility.
AB  - BACKGROUND: Numerous challenges remain to achieve industrially competitive space
      time yields for bio-oxidations. The ability to rapidly screen bioconversion
      reactions for characterization and optimization is of major importance in
      bioprocess development and biocatalyst selection; studies at conventional lab
      scale are time consuming and labor intensive with low experimental throughput.
      The direct omega-oxyfunctionalization of aliphatic alkanes in a regio- and
      chemoselective manner is efficiently catalyzed by monooxygenases such as the
      AlkBGT enzyme complex from Pseudomonas putida under mild conditions. However, the
      adoption of microscale tools for these highly volatile substrates has been
      hindered by excessive evaporation and material incompatibility. RESULTS: This
      study developed and validated a robust high-throughput microwell platform for
      whole-cell two-liquid phase bio-oxidations of highly volatile n-alkanes. Using
      microwell plates machined from polytetrafluoroethylene and a sealing clamp,
      highly reproducible results were achieved with no significant variability such as
      edge effects determined. A design of experiment approach using a response surface
      methodology was adopted to systematically characterize the system and identify
      non-limiting conditions for a whole cell bioconversion of dodecane. Using resting
      E. coli cells to control cell concentration and reducing the fill volume it is
      possible to operate in non-limiting conditions with respect to oxygen and glucose
      whilst achieving relevant total product yields (combining 1-dodecanol, dodecanal
      and dodecanoic acid) of up to 1.5 mmol g DCW-1 . CONCLUSIONS: Overall, the
      developed microwell plate greatly improves experimental throughput, accelerating
      the screening procedures specifically for biocatalytic processes in non
      conventional media. Its simplicity, robustness and standardization ensure high
      reliability of results.

PMID- 29017531
TI  - Can the collection of expired long-lasting insecticidal nets reduce their
      coverage and use? Sociocultural aspects related to LLIN life cycle management and
      use in four districts in Madagascar.
AB  - BACKGROUND: There is growing awareness of the likely impact increased numbers of
      LLINs will have on the environment, if not disposed of or recycled appropriately.
      As part of a World Health Organization (WHO) and United Nations Environment
      Programme (UNEP) pilot study to assess environmentally-sound and cost-effective
      LLIN recycling strategies, the USAID-Deliver Project collected 22,559 used bed
      nets in Madagascar. A social science study was conducted to provide data on socio
      cultural factors related to collection and replacement of LLINs, including impact
      on primary and other net uses. METHODS: Ethnographic exploratory research was
      carried out following the pilot USAID-Deliver net collection and recycling
      campaign in Betioky, Tsihombe, Fenerive Est and Ambanja districts of Madagascar,
      triangulating participant observation, interviewing and group discussions.
      Sampling was theoretical and data analysis was a continuous and iterative process
      concurrent to data collection. Final analysis was conducted using NVivo10.
      RESULTS: The following themes emerged as contributing to the success of
      collecting expired LLINs in the community for recycling purposes: (i) net
      adequacy and preference: characteristic differences between collected and newly
      distributed nets lead to communities' reticence to relinquish old nets before
      confirming new nets were appropriate for intended use. Where newly distributed
      nets failed to meet local requirements, this was expected to increase alternative
      uses and decrease household turn over. (ii) Net collection strategies: the net
      collection campaign brought net use out of the private sphere and into the public
      arena. Net owners reported feeling ashamed when presenting damaged nets in public
      for collection, leading to reduced net relinquishment. (iii) Net lifecycle:
      communities perceived nets as being individually owned and economic value was
      attributed both to good-condition nets for sleeping and to worn nets for
      alternative/secondary purposes. Collecting nets at the stage of waste rather than
      at their prescribed end of life was locally acceptable. CONCLUSION: The
      collection of LLINs for recycling/disposal can lead to lower coverage under
      certain conditions. Collecting used LLINs may be appropriate under the following
      conditions: (i) nets are collected at the stage of waste; (ii) new nets are in
      line with community preferences; and (iii) collection strategies have been agreed
      upon within the community prior to replacement activities. Any
      collection/recycling of old LLINs should be based on in-depth understanding of
      the local context and include participatory processes to prevent reduced
      coverage.

PMID- 29017532
TI  - Sequencing of the complete mitochondrial genome of a fish-parasitic flatworm
      Paratetraonchoides inermis (Platyhelminthes: Monogenea): tRNA gene arrangement
      reshuffling and implications for phylogeny.
AB  - BACKGROUND: Paratetraonchoides inermis (Monogenea: Tetraonchoididae) is a
      flatworm parasitising the gills of uranoscopid fishes. Its morphological
      characteristics are ambiguous, and molecular data have never been used to study
      its phylogenetic relationships, which makes its taxonomic classification
      controversial. Also, several decades of unsuccessful attempts to resolve the
      relationships within the Monogenea present a strong indication that morphological
      datasets may not be robust enough to be used to infer evolutionary histories. As
      the use of molecular data is currently severely limited by their scarcity, we
      have sequenced and characterized the complete mitochondrial (mt) genome of P.
      inermis. To investigate its phylogenetic position, we performed phylogenetic
      analyses using Bayesian inference and maximum likelihood approaches using
      concatenated amino acid sequences of all 12 protein-coding genes on a dataset
      containing all available monogenean mt genomes. RESULTS: The circular mt genome
      of P. inermis (14,654 bp) contains the standard 36 genes: 22 tRNAs, two rRNAs, 12
      protein-encoding genes (PCGs; Atp8 is missing) and a major non-coding region
      (mNCR). All genes are transcribed from the same strand. The A + T content of the
      whole genome (82.6%), as well as its elements, is the highest reported among the
      monogeneans thus far. Three tRNA-like cloverleaf structures were found in mNCR.
      Several results of the phylogenomic analysis are in disagreement with previously
      proposed relationships: instead of being closely related to the Gyrodactylidea,
      Tetraonchidea exhibit a phylogenetic affinity with the Dactylogyridea +
      Capsalidea clade; and the order Capsalidea is neither basal within the subclass
      Monopisthocotylea, nor groups with the Gyrodactylidea, but instead forms a sister
      clade with the Dactylogyridea. The mt genome of P. inermis exhibits a unique gene
      order, with an extensive reorganization of tRNAs. Monogenea exhibit exceptional
      gene order plasticity within the Neodermata. CONCLUSIONS: This study shows that
      gene order within monopisthocotylid mt genomes is evolving at uneven rates, which
      creates misleading evolutionary signals. Furthermore, our results indicate that
      all previous attempts to resolve the evolutionary history of the Monogenea may
      have produced at least partially erroneous relationships. This further
      corroborates the necessity to generate more molecular data for this group of
      parasitic animals.

PMID- 29017535
TI  - The LeucoPatch(r) system in the management of hard-to-heal diabetic foot ulcers:
      study protocol for a randomised controlled trial.
AB  - BACKGROUND: Diabetic foot ulcers are a common and severe complication of diabetes
      mellitus. Standard treatment includes debridement, offloading, management of
      infection and revascularisation where appropriate, although healing times may be
      long. The LeucoPatch(r) device is used to generate an autologous platelet-rich
      fibrin and leucocyte wound dressing produced from the patient's own venous blood
      by centrifugation, but without the addition of any reagents. The final product
      comprises a thin, circular patch composed predominantly of fibrin together with
      living platelets and leucocytes. Promising results have been obtained in non
      controlled studies this system, but this now needs to be tested in a randomised
      controlled trial (RCT). If confirmed, the LeucoPatch(r) may become an important
      new tool in the armamentarium in the management of diabetic foot ulcers which are
      hard-to-heal. METHODS: People with diabetes and hard-to-heal ulcers of the foot
      will receive either pre-specified good standard care or good standard care
      supplemented by the application of the LeucoPatch(r) device. The primary outcome
      will be the percentage of ulcers healed within 20 weeks. Healing will be defined
      as complete epithelialisation without discharge that is maintained for 4 weeks
      and is confirmed by an observer blind to randomisation group. DISCUSSION: Ulcers
      of the foot are a major source of morbidity to patients with diabetes and costs
      to health care economies. The study population is designed to be as inclusive as
      possible with the aim of maximising the external validity of any findings. The
      primary outcome measure is healing within 20 weeks of randomisation and the trial
      also includes a number of secondary outcome measures. Among these are rate of
      change in ulcer area as a predictor of the likelihood of eventual healing, minor
      and major amputation of the target limb, the incidence of infection and quality
      of life. TRIAL REGISTRATION: International Standard Randomised Controlled Trial,
      ISRCTN27665670 . Registered on 5 July 2013.

PMID- 29017533
TI  - Persistent organic pollutants and mortality in the United States, NHANES 1999
      2011.
AB  - BACKGROUND: Persistent organic pollutants (POPs) are environmentally and
      biologically persistent chemicals that include polybrominated diphenyl ethers
      (PBDEs), per- and polyfluoroalkyl substances (PFASs), polychlorinated biphenyls
      (PCBs), and organochlorine (OC) pesticides. Currently, data on the associations
      between exposure to POPs and the risk of mortality in the U.S. population is
      limited. Our objective was to determine if higher exposure to POPs is associated
      with greater risk of all-cause, cancer, heart/cerebrovascular disease, or other
      cause mortality. METHODS: Analyses included participants aged 60 years and older
      from the 1999-2006 National Health and Nutrition Examination Surveys (NHANES). We
      included 483 participants for analyses of PBDEs, 1043 for PFASs, and 461 for
      PCBs, and 1428 for OC pesticides. Exposures to POPs were estimated using
      biomarkers measured in serum. Mortality status through December 31, 2011 was
      obtained from public-use, linked mortality files. We used Cox proportional hazard
      models to quantify the associations of interest. Where we observed an
      association, we explored effect modification by sex, body mass index, smoking
      status, and albuminuria. We also explored the combined effect of PBDEs and OC
      pesticides in the subsample of participants with measures of both analytes.
      RESULTS: Serum measurements of PBDEs, PFASs, and PCBs were not clearly associated
      with increased all-cause or cause-specific mortality in older Americans. Beta
      hexachlorocyclohexane was associated with an increased risk of all-cause
      mortality [HR per 1 SD increase =1.18, 95% CI = 1.01, 1.38]. Oxychlordane [HR =
      1.15 95% CI 1.06, 1.25], p,p'-DDE [HR = 1.12, 95% CI = 1.02, 1.23], trans
      nonachlor [HR = 1.11, 95% CI = 1.04, 1.18], and beta-hexachlorocyclohexane [HR =
      1.25, 95% CI = 1.03, 1.52] were associated with increased risk of other-cause
      mortality. Exploratory analyses suggested associations between OC pesticides and
      other-cause mortality were modified by sex. Exploratory analyses also suggested
      that the combination of high PBDE and high OC pesticide exposure had a stronger
      than expected adverse effect on all-cause mortality. CONCLUSION: Higher exposure
      to beta-hexachlorocyclohexane, an OC pesticide, is associated with increased all
      cause mortality and higher exposure to four OC pesticides is associated with
      increased non-cancer, non-heart/cerebrovascular disease mortality in U.S. adults
      60 years or older. These associations may be modified by sex or exposure to other
      POPs.

PMID- 29017534
TI  - The association between smoking and blood pressure in men: a cross-sectional
      study.
AB  - BACKGROUND: Cigarette smoking is a known risk factor for cardiovascular disease
      (CVD), but the association between smoking and blood pressure is unclear. Thus,
      the current study examined the association between cigarette smoking and blood
      pressure in men. METHODS: Systolic blood pressure (SBP), diastolic blood pressure
      (DBP), mean arterial pressure (MAP) and pulse pressure (PP) were examined using
      digital blood pressure measuring device, and smoking status was determined with
      China National Health Survey. RESULTS: The ANCOVA showed that the adjusted DBP
      and MAP were lower in current smokers versus nonsmokers and the adjusted SBP was
      lower in current smokers versus former smokers (P < 0.05). Additionally, the
      adjusted PP tend to be decreased steadily as the pack.years increased in current
      smokers. In a fully adjusted logistic regression model, former smokers had
      increased ORs (95% CI) of 1.48 (1.01, 2.18) of hypertension and current smokers
      had not increased ORs (95% CI) of 0.83 (0.61, 1.12), compared with never smokers.
      CONCLUSIONS: The findings revealed that the adjusted blood pressure were lower in
      current smokers versus nonsmokers and former smokers. No significant dose
      dependent effect of current smoking on blood pressure indices except PP was
      observed. Smoking cessation was significantly associated with an increased risk
      of hypertension. However, current smoking was not a risk factor of hypertension.

PMID- 29017537
TI  - Assessing bed net damage: comparisons of three measurement methods for estimating
      the size, shape, and distribution of holes on bed nets.
AB  - BACKGROUND: Measuring the physical condition of long-lasting insecticidal nets
      (LLINs) under field conditions is of great importance for malaria control
      programmes to guide decisions on how frequently to replace LLINs. Current
      guidelines by the World Health Organization Pesticide Evaluation Scheme (WHOPES)
      propose a proportionate hole index (pHI) for assessing LLIN condition by counting
      the number of holes the size of a thumb, fist, head, and larger than a head.
      However, this method does not account for irregular hole shapes or exact hole
      sizes which could result in inaccurate decisions about when to replace LLINs.
      METHODS: LLINs were collected during a 2013 health facility-based malaria case
      control study in Machinga District, Malawi. To evaluate the accuracy of the pHI,
      the physical condition of 277 LLINs was estimated by the WHOPES method and then
      compared with two more thorough measurement methods: image analysis of digital
      photographs of each LLIN side; and for 10 nets, ruler measurements of the length,
      width, and location of each hole. Total hole counts and areas per net were
      estimated by each method, and detailed results of hole shapes and composite
      pictures of hole locations were generated using image analysis. RESULTS: The
      WHOPES method and image analysis resulted in similar estimates of total hole
      counts, each with a median of 10 (inter-quartile range (IQR) 4-24 and 4-23,
      respectively; p = 0.004); however, estimated hole areas were significantly larger
      using the WHOPES method (median 162 cm2, IQR 28-793) than image analysis (median
      13 cm2, IQR 3-101; p < 0.0001). The WHOPES method classified fewer LLINs in 'good
      condition' compared to image analysis (42% vs 74%). The ruler method detected
      significantly more holes than image analysis did (p = 0.002) in 10 LLINs;
      however, total hole area was not significantly different (p = 0.16). Most holes
      were not circular but roughly 2-5 times longer in one direction. The lower
      quarter of LLIN sides was found to have the most holes. CONCLUSIONS: The WHOPES
      method overestimated total hole area, likely because holes are elongated rather
      than circular, suggesting further adjustments to the pHI formula may be warranted
      when considering LLIN replacement strategies.

PMID- 29017536
TI  - A strongly selected mutation in the HIV-1 genome is independent of T cell
      responses and neutralizing antibodies.
AB  - BACKGROUND: Mutations rapidly accumulate in the HIV-1 genome after infection.
      Some of those mutations are selected by host immune responses and often cause
      viral fitness losses. This study is to investigate whether strongly selected
      mutations that are not associated with immune responses result in fitness losses.
      RESULTS: Strongly selected mutations were identified by analyzing 5'-half HIV-1
      genome (gag/pol) sequences from longitudinal samples of subject CH0131. The K43R
      mutation in the gag gene was first detected at day 91 post screening and was
      fixed in the viral population at day 273 while the synonymous N323tc mutation was
      first detected at day 177 and fixed at day 670. No conventional or cryptic T cell
      responses were detected against either mutation sites by ELISpot analysis.
      However, when fitness costs of both mutations were measured by introducing each
      mutation into their cognate transmitted/founder (T/F) viral genome, the K43R
      mutation caused a significant fitness loss while the N323tc mutation had little
      impact on viral fitness. CONCLUSIONS: The rapid fixation, the lack of detectable
      immune responses and the significant fitness cost of the K43R mutation suggests
      that it was strongly selected by host factors other than T cell responses and
      neutralizing antibodies.

PMID- 29017538
TI  - HGF potentiates extracellular matrix-driven migration of human myoblasts:
      involvement of matrix metalloproteinases and MAPK/ERK pathway.
AB  - BACKGROUND: The hepatocyte growth factor (HGF) is required for the activation of
      muscle progenitor cells called satellite cells (SC), plays a role in the
      migration of proliferating SC (myoblasts), and is present as a soluble factor
      during muscle regeneration, along with extracellular matrix (ECM) molecules. In
      this study, we aimed at determining whether HGF is able to interact with ECM
      proteins, particularly laminin 111 and fibronectin, and to modulate human
      myoblast migration. METHODS: We evaluated the expression of the HGF-receptor c
      Met, laminin, and fibronectin receptors by immunoblotting, flow cytometry, or
      immunofluorescence and used Transwell assays to analyze myoblast migration on
      laminin 111 and fibronectin in the absence or presence of HGF. Zymography was
      used to check whether HGF could modulate the production of matrix
      metalloproteinases by human myoblasts, and the activation of MAPK/ERK pathways
      was evaluated by immunoblotting. RESULTS: We demonstrated that human myoblasts
      express c-Met, together with laminin and fibronectin receptors. We observed that
      human laminin 111 and fibronectin have a chemotactic effect on myoblast
      migration, and this was synergistically increased when low doses of HGF were
      added. We detected an increase in MMP-2 activity in myoblasts treated with HGF.
      Conversely, MMP-2 inhibition decreased the HGF-associated stimulation of cell
      migration triggered by laminin or fibronectin. HGF treatment also induced in
      human myoblasts activation of MAPK/ERK pathways, whose specific inhibition
      decreased the HGF-associated stimulus of cell migration triggered by laminin 111
      or fibronectin. CONCLUSIONS: We demonstrate that HGF induces ERK phosphorylation
      and MMP production, thus stimulating human myoblast migration on ECM molecules.
      Conceptually, these data state that the mechanisms involved in the migration of
      human myoblasts comprise both soluble and insoluble moieties. This should be
      taken into account to optimize the design of therapeutic cell transplantation
      strategies by improving the migration of donor cells within the host tissue, a
      main issue regarding this approach.

PMID- 29017539
TI  - Contraceptive knowledge, perceptions, and concerns among men in Uganda.
AB  - BACKGROUND: Low contraceptive uptake and high unmet need for contraception remain
      significant issues in Uganda compared to neighboring countries such as Kenya,
      Ethiopia, and Rwanda. Although prior research on contraceptive uptake has
      indicated that male partners strongly influence women's decisions around
      contraceptive use, there is limited in-depth qualitative research on knowledge
      and concerns regarding modern contraceptive methods among Ugandan men. METHODS:
      Using in-depth interviews (N = 41), this qualitative study investigated major
      sources of knowledge about contraception and perceptions of contraceptive side
      effects among married Ugandan men. RESULTS: Men primarily reported knowledge of
      contraceptives based on partner's experience of side effects, partner's knowledge
      from health providers and mass media campaigns, and partner's knowledge from her
      peers. Men were less likely to report contraceptive knowledge from health care
      providers, mass media campaigns, or peers. Men's concerns about various
      contraceptive methods were broadly associated with failure of the method to work
      properly, adverse health effects on women, and severe adverse health effects on
      children. Own or partner's human immunodeficiency virus (HIV) status did not
      impact on contraceptive knowledge. CONCLUSIONS: Overall, we found limited
      accurate knowledge about contraceptive methods among men in Uganda. Moreover,
      fears about the side effects of modern contraceptive methods appeared to be
      common among men. Family planning services in Uganda could be significantly
      strengthened by renewed efforts to focus on men's knowledge, fears, and
      misconceptions.

PMID- 29017540
TI  - Only half of the mothers practiced early initiation of breastfeeding in Northwest
      Ethiopia, 2015.
AB  - BACKGROUND: Early initiation of breastfeeding has been well-recognized in
      reducing neonatal mortality; however, it remains sub-optimal in Ethiopia. This
      study therefore assessed the prevalence of early initiation of breastfeeding and
      associated factors among mothers with children aged 6-24 months in Dabat Health
      and Demographic Surveillance System (HDSS) site, northwest Ethiopia, where
      literature on the issue is markedly scarce. METHODS: This community-based cross
      sectional survey was carried out from May to June, 2015, at Dabat HDSS site,
      Dabat District. Eight hundred twenty-two mother-child pairs were included in the
      study. A multivariable logistic regression model was employed to identify factors
      associated with early initiation of breastfeeding. RESULTS: This study
      demonstrated that the prevalence of early initiation of breastfeeding was 53.3%.
      Institutional delivery (AOR = 4.9; 95% CI 3.2, 7.4), higher Infant and Young
      Child Feeding (IYCF) knowledge (AOR = 2.3; 95% CI 1.6, 3.3), higher wealth status
      (AOR = 4.1, 95% CI 2.8, 6.0) and low fathers' education (AOR = 0.3, 95% CI 0.2,
      0.6) were significantly associated with early initiation of breastfeeding in the
      multivariate analysis. CONCLUSION: In summary, the coverage of early initiation
      of breastfeeding in Dabat HDSS site was low, considerably below the national
      target. Therefore, efforts should be intensified to step-up early initiation of
      breastfeeding by focusing on the identified determinants.

PMID- 29017541
TI  - Cardiovascular flukes (Trematoda: Spirorchiidae) in Caretta caretta Linnaeus,
      1758 from the Mediterranean Sea.
AB  - BACKGROUND: The northern Adriatic Sea represents one of the most important
      neritic foraging grounds for the loggerhead sea turtle Caretta caretta L. in the
      Mediterranean Sea. Four genera of blood flukes with variable prevalence and
      pathogenic impact have been reported worldwide in this species. Hapalotrema
      Looss, 1899 and Amphiorchis Price, 1934 are the only two genera reported in
      Mediterranean waters; however, updated data describing spirorchiidiasis in the
      central and eastern Mediterranean and infection prevalence are still lacking.
      This work aimed to investigate the presence and pathology of spirorchiidiasis in
      C. caretta in the Mediterranean Sea. METHODS: One hundred sixty-eight animals
      stranded along the northwestern Adriatic coast between 2009 and 2015 were
      submitted to necropsy and subsequent analyses for the detection of adult flukes,
      detection of eggs in the faeces and spleen and histopathology. Molecular analyses
      were carried out on hosts (mitochondrial D-loop) and parasites (28S gene and ITS2
      spacer) to trace the turtle origins and identify the fluke phylogenetic
      relationships. RESULTS: Spirorchiidiasis was detected in 16.7% of the animals.
      Hapalotrema mistroides (Monticelli, 1899) and Neospirorchis sp. were found in
      twenty-six and ten cases, respectively. Adult flukes were found in six cases,
      while eggs were detectable through copromicroscopic examination for all infected
      turtles, and the results for the detection of eggs in the spleen agreed with the
      copromicroscopic analysis. Only mild lesions were observed. Eggs of types 1 and 3
      were grossly visible in the gastrointestinal mucosa, vasculitis was rarely
      observed in the heart and great vessels, and multifocal granulomas were
      widespread in the tissues. Molecular identification unambiguously assigned the
      spirorchiid samples to H. mistroides and Neospirorchis sp. Genetic
      characterization of loggerhead mtDNA pointed to a Mediterranean origin of the
      turtle hosts. CONCLUSION: This survey provides new data on the spread of
      spirorchiidiasis in the Mediterranean loggerhead sea turtle population and
      reports for the first time the presence of Neospirorchis spp. in this basin. The
      infections did not have a causal effect on the death nor a strong impact on the
      general health status of the animals.

PMID- 29017542
TI  - Financial burden of healthcare for cancer patients with social medical insurance:
      a multi-centered study in urban China.
AB  - BACKGROUND: Cancer accounts for one-fifth of the total deaths in China and brings
      heavy financial burden to patients and their families. Chinese government has
      made strong commitment to develop three types of social medical insurance since
      1997 and recently, more attempts were invested to provide better financial
      protection. To analyze health services utilization and financial burden of
      insured cancer patients, and identify the gaps of financial protection provided
      by insurance in urban China. METHODS: A random sampling, from Urban Employee's
      Basic Medical Insurance claim database, was performed in 4 cities in 2008 to
      obtain insurance claim records of cancer patients. Services utilization, medical
      expenses and out-of-pocket (OOP) payment were the metrics collected from the
      insurance claim database, and household non-subsistence expenditure were
      estimated from Health Statistics. Catastrophic health expenditure was defined as
      household's total out-of-pocket payments exceed 40% of non-subsistence
      expenditure. Stratified analysis by age groups was performed on service use,
      expenditure and OOP payment. RESULTS: Data on 2091 insured cancer patients were
      collected. Reimbursement rates were over 80% for Shanghai and Beijing while
      Fuzhou and Chongqing only covered 60%-70% of total medical expenditure. Shanghai
      had the highest reimbursement rate (88.2%), high total expenditure ($1228) but
      lowest OOP payment ($170) among the four cities. Chongqing and Fuzhou's insured
      cancer patients exclusively preferred tertiary hospitals for outpatient services.
      Fuzhou led the annual total medical expense ($9963), followed by Chongqing,
      Beijing and Shanghai. The average OOP as proportion of household's capacity to
      pay was 87.3% (Chongqing), 66.0% (Fuzhou), 33.7% (Beijing) and 19.6% (Shanghai).
      Elderly insured cancer patients utilized fewer outpatient services, had lower
      number of inpatient admissions but longer length of stay, and higher total
      expenditure. CONCLUSIONS: Social economic development was not necessarily
      associated with total medical expense but determined the level of financial
      protection. The economic burden of insured cancer patients was reduced by
      insurance but it is still necessary to provide further financial protections and
      improve affordability of healthcare for cancer patients in China.

PMID- 29017544
TI  - Sero-prevalence and intrinsic factors associated with Brucella infection in food
      animals slaughtered at abattoirs in Abuja, Nigeria.
AB  - BACKGROUND: Brucellosis, a neglected tropical food-borne zoonotic disease, has a
      negative impact on both animal and human health as well as tremendous socio
      economic impact in developing countries where rural income relies largely on
      livestock breeding and dairy products. It is endemic in the animal population in
      Nigeria and is a recognized occupational hazard. This work was done to establish
      the sero-prevalence and predisposing factors of food animals in Abuja, Nigeria to
      Brucella infection. RESULTS: Of 376 cattle, 203 sheep and 260 goats screened, 21
      (5.6%); 19 (9.4%); 51 (19.6%) were positive, respectively for brucellosis with
      Rose Bengal Plate Test, and 2 (0.5%); 4 (2.0%); 10 (3.8%), respectively with c
      ELISA. The likelihood of acquiring Brucella infection was higher among the Red
      Sokoto breed of goats compared to other breeds of goats (p = 0.05). CONCLUSION:
      This study showed that the prevalence of Brucella infection was low in food
      animals slaughtered at abattoirs in Abuja. However, of all animals screened,
      seropositivity to Brucella infection was highest in goats with Red Sokoto breed
      of goats more likely to acquire the disease when compared to other breeds.

PMID- 29017543
TI  - Plasmodium falciparum uses vitamin E to avoid oxidative stress.
AB  - BACKGROUND: Plasmodium falciparum is sensitive to oxidative stress in vitro and
      in vivo, and many drugs such as artemisinin, chloroquine and cercosporin
      interfere in the parasite's redox system. To minimize the damage caused by
      reactive radicals, antioxidant enzymes and their substrates found in parasites
      and in erythrocytes must be functionally active. It was shown that P. falciparum
      synthesizes vitamin E and that usnic acid acts as an inhibitor of its
      biosynthesis. Vitamin E is a potent antioxidant that protects polyunsaturated
      fatty acids from lipid peroxidation, and this activity can be measured by
      detecting its oxidized product and by evaluating reactive oxygen species (ROS)
      levels. RESULTS: Here, we demonstrated that ROS levels increased in P. falciparum
      when vitamin E biosynthesis was inhibited by usnic acid treatment and decreased
      to basal levels if exogenous vitamin E was added. Furthermore, we used metabolic
      labelling to demonstrate that vitamin E biosynthesized by the parasite acts as an
      antioxidant since we could detect its radiolabeled oxidized product. The
      treatment with chloroquine or cercosporin of the parasites increased the ratio
      between alpha-tocopherolquinone and alpha-tocopherol. CONCLUSIONS: Our findings
      demonstrate that vitamin E produced endogenously by P. falciparum is active as an
      antioxidant, probably protecting the parasite from the radicals generated by
      drugs.

PMID- 29017545
TI  - Little pigeons can carry great messages: potential distribution and ecology of
      Uranotaenia (Pseudoficalbia) unguiculata Edwards, 1913 (Diptera: Culicidae), a
      lesser-known mosquito species from the Western Palaearctic.
AB  - BACKGROUND: Uranotaenia unguiculata is a Palaearctic mosquito species with poorly
      known distribution and ecology. This study is aimed at filling the gap in our
      understanding of the species potential distribution and its environmental
      requirements through a species distribution modelling (SDM) exercise.
      Furthermore, aspects of the mosquito ecology that may be relevant to the
      epidemiology of certain zoonotic vector-borne diseases in Europe are discussed.
      RESULTS: A maximum entropy (Maxent) modelling approach has been applied to
      predict the potential distribution of Ur. unguiculata in the Western Palaearctic.
      Along with the high accuracy and predictive power, the model reflects well the
      known species distribution and predicts as highly suitable some areas where the
      occurrence of the species is hitherto unknown. CONCLUSIONS: To our knowledge, the
      potential distribution of a mosquito species from the genus Uranotaenia is
      modelled for the first time. Provided that Ur. unguiculata is a widely
      distributed species, and some pathogens of zoonotic concern have been detected in
      this mosquito on several occasions, the question regarding its host associations
      and possible epidemiological role warrants further investigation.

PMID- 29017547
TI  - Reconstructing cancer drug response networks using multitask learning.
AB  - BACKGROUND: Translating in vitro results to clinical tests is a major challenge
      in systems biology. Here we present a new Multi-Task learning framework which
      integrates thousands of cell line expression experiments to reconstruct drug
      specific response networks in cancer. RESULTS: The reconstructed networks
      correctly identify several shared key proteins and pathways while simultaneously
      highlighting many cell type specific proteins. We used top proteins from each
      drug network to predict survival for patients prescribed the drug. CONCLUSIONS:
      Predictions based on proteins from the in-vitro derived networks significantly
      outperformed predictions based on known cancer genes indicating that Multi-Task
      learning can indeed identify accurate drug response networks.

PMID- 29017548
TI  - Mycobacterium tuberculosis infection in cattle from the Eastern Cape Province of
      South Africa.
AB  - BACKGROUND: Mycobacterium tuberculosis is the main causative agent of
      tuberculosis (TB) in human and Mycobacterium bovis commonly causes tuberculosis
      in animals. Transmission of tuberculosis caused by both pathogens can occur from
      human to animals and vice versa. RESULTS: In the current study, M. tuberculosis,
      as confirmed by polymerase chain reaction (PCR) using primers targeting 3 regions
      of difference (RD4, RD9 and RD12) on the genomes, was isolated from cattle
      originating from two epidemiologically unrelated farms in the Eastern Cape (E.C)
      Province of South Africa. Although the isolates were genotyped with variable
      number of tandem repeat (VNTR) typing, no detailed epidemiological investigation
      was carried out on the respective farms to unequivocally confirm or link humans
      as sources of TB transmission to cattle, a move that would have embraced the 'One
      Health' concept. In addition, strain comparison with human M. tuberculosis in the
      database from the E.C Province and other provinces in the country did not reveal
      any match. CONCLUSIONS: This is the first report of cases of M. tuberculosis
      infection in cattle in South Africa. The VNTR profiles of the M. tuberculosis
      strains identified in the current study will form the basis for creating M.
      tuberculosis VNTR database for animals including cattle for future
      epidemiological studies. Our findings however, call for urgent reinforcement of
      collaborative efforts between the veterinary and the public health services of
      the country.

PMID- 29017549
TI  - Enhanced hospital-based learning at a medical school through application of
      management principles - a case study.
AB  - BACKGROUND: A hospital with all its brimming activity constitutes a unique
      learning environment for medical students. However, to organise high-quality
      education within this context is a task of great complexity. This paper describes
      a teaching hospital case, where management principles were applied to enhance the
      learning quality of medical education. METHODS: Traditional attempts from the
      faculty had been unsuccessful in improving learning among medical students at a
      teaching hospital. We therefore applied management principles to be able to
      improve the learning quality. An evaluation was performed from the perspectives
      of management (course directors/ heads of health care departments), medical
      students, and physician supervisors. Presages were defined, including educational
      resources and management; processes were adjusted, including learning activities
      and staff schedules; and products were assessed. RESULTS: Charting and
      benchmarking the use of local educational resources identified unused funding.
      Structured recurrent collaboration within resource utilization was established
      between course directors and heads of all concerned health care departments. By
      formulating a joint agreement, the identified assets were used to reorganise the
      course, to create constructive alignment, and to increase assigned supervisor
      time. This resulted in a sustainable improvement of learning quality and culture.
      CONCLUSION: By using management principles in combination with a scholarship of
      teaching and learning, it was possible to locate and redistribute educational
      resources in an effective way. This improved student learning and the learning
      culture of the health care departments. We propose that such an initiative could
      also be transferable to other contexts. Faculty leaders facing similar problems
      should consider the advantages of a structured collaboration with health care
      department heads.

PMID- 29017550
TI  - Improving family planning services delivery and uptake: experiences from the
      "Reversing the Stall in Fertility Decline in Western Kenya Project".
AB  - OBJECTIVE: In this paper, we reflect on our experiences of implementing a
      multipronged intervention to improve sexual and reproductive health outcomes. The
      project used family planning as its entry point and was implemented in two high
      fertility counties-Busia and Siaya in Kenya. The intervention, implemented by a
      seven-member consortium, involved: family planning services delivery; regular
      training of service providers to deliver high quality services; monitoring and
      evaluation; strengthening of commodity chain delivery and forecasting; school
      based and out-of-school based sexuality education; and advocacy and stakeholder
      engagements at the community, county and national levels. RESULTS: Over a 5-year
      period, the project contributed to raising demand for family planning
      considerably, evidenced in fertility decline. It also improved the capacity of
      family planning services providers, increased commitment and awareness of county
      government and other community stakeholders on the importance of investments in
      family planning. Our collaborations with organisations interested in sexual and
      reproductive health issues substantially enhanced the consortium's ability to
      increase demand for, and supply of family planning commodities. These
      collaborations are proving useful in the continuity and sustainability of project
      achievements.

PMID- 29017551
TI  - Comparative efficacy of the LeucofeligenTM FeLV/RCP and PurevaxTM RCP FeLV
      vaccines against infection with circulating feline Calicivirus.
AB  - BACKGROUND: Feline calicivirus (FCV) is a common virus, found worldwide, mainly
      responsible for chronic ulceroproliferative faucitis and periodontitis. This
      virus has a high mutation rate, leading to the presence of numerous FCV strains
      in the field. The objectives of this study was to evaluate and compare the
      efficacy of two vaccines (LeucofeligenTM FeLV/RCP and PurevaxTM RCP FeLV), which
      differ by their nature (live vs. inactivated) and the vaccinal strains, against
      circulating FCV strains. Thirty 9-week-old specific pathogen free (SPF) kittens
      were thus randomised into 3 groups and were either not vaccinated (control) or
      vaccinated (2 injections, 3 weeks apart) with one of the vaccines. Four weeks
      after the second injection of primary vaccination, the cats were inoculated with
      a pathogenic strain representative of the ones circulating in Europe (FCV-FR4_01)
      and followed for 2 weeks. RESULTS: After challenge, significant differences (p <
      0.05) between control cats and cats vaccinated with LeucofeligenTM FeLV/RCP or
      PurevaxTM RCP FeLV were observed for body weight variation, rectal temperature
      rise and maximum clinical scores, reflecting the intensity of the signs (83% and
      67% lower in the respective vaccinated groups than in the control group).
      Significant differences were observed between the vaccinated groups, as cats
      vaccinated with LeucofeligenTM FeLV/RCP had a lower temperature rise (p < 0.05 at
      days post-challenge 3 to 5) and lower virus shedding titres (p < 0.05 at days
      post-challenge 8, 9 and 11) than cats vaccinated with PurevaxTM RCP FeLV.
      Finally, only cats vaccinated with LeucofeligenTM FeLV/RCP had a significantly
      lower cumulative score, reflecting the intensity and duration of calicivirosis
      clinical signs, than the control cats (77% lower vs. 62% lower for cats
      vaccinated with PurevaxTM RCP FeLV). CONCLUSIONS: Both vaccines, LeucofeligenTM
      FeLV/RCP and PurevaxTM RCP FeLV, were found to be efficacious in reducing
      clinical signs induced by FCV-FR4_01, a FCV strain representative of the
      circulating ones. However, cats vaccinated with LeucofeligenTM FeLV/RCP were able
      to control the infection more efficiently than those vaccinated with PurevaxTM
      RCP FeLV, as evidenced by the shorter duration of clinical signs and lower viral
      titre in excretions.

PMID- 29017552
TI  - Syphilis in the Americas: a protocol for a systematic review of syphilis
      prevalence and incidence in four high-risk groups, 1980-2016.
AB  - BACKGROUND: Syphilis infection has recently resurfaced as a significant public
      health problem. Although there has been a tremendous amount of research on the
      epidemiology of syphilis, there has been limited work done to synthesize the
      extensive body of research and systematically estimate patterns of disease within
      high-risk groups in the Americas. The purpose of this systematic review and meta
      analysis is to (1) summarize recent patterns of syphilis infection in North and
      South America among four high-risk groups (MSM, transgender women, sex workers,
      and incarcerated individuals) from 1980 to 2016, (2) identify and differentiate
      regional geographic epidemiologic characteristics, and (3) compare the epidemics
      of the economically developed countries of North America from the developing
      countries and public health systems of Latin America and the Caribbean.
      METHODS/DESIGN: Primary studies reporting syphilis prevalence and/or incidence in
      at least one of the four high-risk groups will be identified from Medline/PubMed,
      Embase, Lilacs, SciELO, The Cochrane Library, Web of Science, Scopus, ProQuest,
      CINAHL, Clase, and Periodica, as well as "gray" literature sources (conference
      abstracts, country reports, etc.). Studies published from 1980 through 2016 will
      be included. Data will be extracted from studies meeting inclusion and exclusion
      criteria and a random effects meta-analysis of prevalence and incidence estimates
      will be conducted. Heterogeneity, risk of bias, and publication bias will be
      assessed. Pooled prevalence and incidence estimates will be calculated for
      comparisons based on geographic region, risk factors, and time period.
      DISCUSSION: Our systematic review and meta-analysis aims to contribute to an
      improved understanding of global epidemiologic patterns of syphilis infection in
      most-at-risk populations. Through systematic classification of the existing
      literature, and comparison of disease patterns across regional, temporal and
      socio-behavioral differences, we hope to improve public health surveillance and
      improve efforts to control the spread of disease across the Americas. SYSTEMATIC
      REVIEW REGISTRATION: PROSPERO CRD42016047306.

PMID- 29017553
TI  - Which phenotypic traits of resistance should be improved in cattle to control
      paratuberculosis dynamics in a dairy herd: a modelling approach.
AB  - Paratuberculosis is a worldwide disease causing production losses in dairy cattle
      herds. Variability of cattle response to exposure to Mycobacterium avium subsp.
      paratuberculosis (Map) has been highlighted. Such individual variability could
      influence Map spread at larger scale. Cattle resistance to paratuberculosis has
      been shown to be heritable, suggesting genetic selection could enhance disease
      control. Our objective was to identify which phenotypic traits characterising the
      individual course of infection influence Map spread in a dairy cattle herd. We
      used a stochastic mechanistic model. Resistance consisted in the ability to
      prevent infection and the ability to cope with infection. We assessed the effect
      of varying (alone and combined) fourteen phenotypic traits characterising the
      infection course. We calculated four model outputs 25 years after Map
      introduction in a naive herd: cumulative incidence, infection persistence, and
      prevalence of infected and affected animals. A cluster analysis identified
      influential phenotypes of cattle resistance. An ANOVA quantified the contribution
      of traits to model output variance. Four phenotypic traits strongly influenced
      Map spread: the decay in susceptibility with age (the most effective), the
      quantity of Map shed in faeces by high shedders, the incubation period duration,
      and the required infectious dose. Interactions contributed up to 12% of output
      variance, highlighting the expected added-value of improving several traits
      simultaneously. Combinations of the four most influential traits decreased
      incidence to less than one newly infected animal per year in most scenarios.
      Future genetic selection should aim at improving simultaneously the most
      influential traits to reduce Map spread in cattle populations.

PMID- 29017555
TI  - Hospital-visiting pregnant women signal an increased spread of hepatitis C
      infection in Khyber Pakhtunkhwa region of Pakistan.
AB  - BACKGROUND: Seroprevalence of hepatitis C in Khyber Pakhtunkhwa province of
      Pakistan was determined by screening blood samples of expectant mothers seeking
      antenatal care in gynecological units of district hospitals. The rationale behind
      this cohort study was that the availability of free-of-cost antenatal care in
      district hospitals brings expectant mothers from a broader geographical range in
      each district and thus provides a large sample-size of healthy pregnant women of
      known medical history for Hepatitis C Virus (HCV) surveillance. The study was
      carried out along a south west to north east transact of five districts, Kohat
      Peshawar-Nowshera-Charsadda-Mardan, with the central district Peshawar and outer
      districts Kohat and Mardan bordering northern mountainous ranges of the Khyber
      Pakhtunkhwa province. This distribution of districts along the transact allowed
      the study to gauge the impact of proximity to remote highland communities on the
      HCV burden of visiting pregnant women tested for HCV infection. METHODS: The
      cohort study randomly selected 150 pregnant women visiting each hospital for
      serological screening for Anti-HCV carried out by ELISA assay. The feasibility of
      ICT and RT-PCR assays for HCV prevalence was also examined in the present study.
      RESULTS: With a total of 750 blood specimen screened, the results of ELISA tests
      revealed a staggering 5.9% frequency of Anti-HCV in the five districts with the
      frequency of ELISA positive cases ranging from 3.3% in Nowshera, 4.7% in
      Charsadda, 6.0% in Peshawar, 6.7% in Kohat, and 8.7% in Mardan. The relatively
      higher frequencies of Anti-HCV cases among hospital visiting pregnant women in
      Peshawar, Kohat and Mardan were consistent with the proximity of these hospitals
      to the highland communities in the bordering mountain ranges. Compared to 44 Anti
      HCV positive serologic specimens detected by ELISA, only 26 and 10 blood
      specimens were tested positive by ICT and PCR methods, respectively. Our study
      validates ELISA as a reliable diagnostic technique for both acute and chronic HCV
      infection. CONCLUSION: The HCV infection rate of 5.9% in Khyber Pakhtunkhwa
      province clearly exceeds the HCV prevalence rates reported for other regions in
      Pakistan, making this province a hotspot of HCV infection in the country.

PMID- 29017554
TI  - In vivo anti-malarial activity and toxicity studies of triterpenic esters
      isolated form Keetia leucantha and crude extracts.
AB  - BACKGROUND: Considering the need for new anti-malarial drugs, further
      investigations on Keetia leucantha (Rubiaceae), an in vitro antiplasmodial plant
      traditionally used to treat malaria, were carried out. This paper aimed to assess
      the in vivo anti-malarial efficacy of K. leucantha triterpenic esters previously
      identified as the most in vitro active components against Plasmodium falciparum
      and their potential toxicity as well as those of anti-malarial extracts. RESULTS:
      These eight triterpenic esters and the major antiplasmodial triterpenic acids,
      ursolic and oleanolic acids, were quantified in the twigs dichloromethane extract
      by validated HPLC-UV methods. They account for about 19% of this extract (16.9%
      for acids and 1.8% for esters). These compounds were also identified in trace in
      the twigs decoction by HPLC-HRMS. Results also showed that extracts and esters
      did not produce any haemolysis, and were devoid of any acute toxicity at a total
      cumulative dose of 800 and 150 mg/kg respectively. Moreover, esters given
      intraperitoneally at 50 mg/kg/day to Plasmodium berghei-infected mice showed a
      very significant (p < 0.01) parasitaemia inhibition (27.8 +/- 5.4%) on day 4 post
      infection compared to vehicle-treated mice. CONCLUSIONS: These results bring out
      new information on the safety of K. leucantha use and on the identification of
      anti-malarial compounds from its dichloromethane extract. Its activity can be
      explained by the presence of triterpenic acids and esters which in vivo activity
      and safety were demonstrated for the first time.

PMID- 29017556
TI  - Evidence for host specificity of Theileria capreoli genotypes in cervids.
AB  - Data on the prevalence of piroplasms in buffaloes and large game animal species
      are lacking from several central European countries. Therefore, to investigate
      the presence of Babesia/Theileria DNA in these hosts, 239 blood and 270 spleen
      samples were taken from cervids (red, fallow, and roe deer), as well as from
      water buffaloes, mouflons, and wild boars in southwestern Hungary, followed by
      DNA extraction and molecular analysis for piroplasms. All samples from buffaloes
      and wild boars were PCR negative. Based on spleen samples, the prevalence of
      piroplasms was significantly higher in red deer (41.7%) than in fallow deer
      (23.5%). Two genotypes of Theileria capreoli were identified, which showed
      significant association with their host species (i.e. genotype "capreoli-CE1" was
      exclusively found in roe deer, whereas red and fallow deer harbored only genotype
      "elaphi-CE1"). Genotype "elaphi-CE1" of T. capreoli was also detected in one
      mouflon. No Babesia spp. were identified. In conclusion, in the evaluated region,
      genotypes of T. capreoli show host-associations among cervids, and at least one
      of these genotypes may infect mouflons.

PMID- 29017557
TI  - Organizational participatory research: a systematic mixed studies review exposing
      its extra benefits and the key factors associated with them.
AB  - BACKGROUND: In health, organizational participatory research (OPR) refers to
      health organization members participating in research decisions, with university
      researchers, throughout a study. This non-academic partner contribution to the
      research may take the form of consultation or co-construction. A drawback of OPR
      is that it requires more time from all those involved, compared to non
      participatory research approaches; thus, understanding the added value of OPR, if
      any, is important. Thus, we sought to assess whether the OPR approach leads to
      benefits beyond what could be achieved through traditional research. METHODS: We
      identified, selected, and appraised OPR health literature, and at each stage, two
      team members independently reviewed and coded the literature. We used
      quantitative content analysis to transform textual data into reliable numerical
      codes and conducted a logistic regression to test the hypothesis that a co
      construction type OPR study yields extra benefits with a greater likelihood than
      consultation-type OPR studies. RESULTS: From 8873 abstracts and 992 full text
      papers, we distilled a sample of 107 OPR studies. We found no difference between
      the type of organization members' participation and the likelihood of exhibiting
      an extra benefit. However, the likelihood of an OPR study exhibiting at least one
      extra benefit is quadrupled when the impetus for the study comes from the
      organization, rather than the university researcher(s), or the organization and
      the university researcher(s) together (OR = 4.11, CI = 1.12-14.01). We also
      defined five types of extra benefits. CONCLUSIONS: This review describes the
      types of extra benefits OPR can yield and suggests these benefits may occur if
      the organization initiates the OPR. Further, this review exposes a need for OPR
      authors to more clearly describe the type of non-academic partner participation
      in key research decisions throughout the study. Detailed descriptions will
      benefit others conducting OPR and allow for a re-examination of the relationship
      between participation and extra benefits in future reviews.

PMID- 29017558
TI  - Stress, health and quality of life of female migrant domestic workers in
      Singapore: a cross-sectional study.
AB  - BACKGROUND: There is a global increase in migrant workers. In Singapore, there
      are over 230,000 migrant domestic workers (MDWs). Female MDWs may experience high
      levels of stress and social isolation, which may negatively impact on their
      health and quality of life. There have also been documented cases of abuse and
      exploitation. However, there is a lack of empirical research with this
      population. This study aimed to investigate factors impacting on the health and
      quality of life of female MDWs in Singapore, including socio-demographic and job
      related characteristics, stress, social isolation, and working management style.
      METHODS: A cross-sectional survey was carried out with 182 female MDWs in
      Singapore. The survey examined health and quality of life (WHOQoL-Bref), social
      connectedness (the Friendship Scale), and preferred and experienced working
      management style (the Theory X and Theory Y Questionnaire). Descriptive analyses
      were carried out in addition to ANOVA, t-tests, and chi-square tests, followed by
      a multivariate analysis using linear regression. RESULTS: Participants were found
      to have good overall quality of life and satisfaction with health. Age and
      working experience were found to be significantly (p < 0.05) associated with
      overall quality of life and three domains (psychological, social, and
      environmental health). Agreement between experienced and preferred working
      management style was also found to be associated with higher quality of life
      scores (with the exception of the social relationships domain). Though women
      reported relatively good overall quality of life, more than half of participants
      reported feeling stressed. In addition, nearly 20% of participants reported being
      isolated or very isolated. Stress was identified to be associated with isolation.
      In the multivariate analysis, stress was found to contribute to worse quality of
      life in all domains except social relationships, after adjusting for confounders.
      Social connectedness was positively associated with all domains of quality of
      life, and agreement of working management style was positively associated with
      physical health, psychological health and environmental quality of life.
      CONCLUSIONS: The findings serve as an evidence-base pointing to the need for
      policies aimed at decreasing stress and social isolation among female MDWs in
      order to improve their health and quality of life.

PMID- 29017559
TI  - Salidroside protects against foam cell formation and apoptosis, possibly via the
      MAPK and AKT signaling pathways.
AB  - BACKGROUND: Foam cell formation and apoptosis are closely associated with
      atherosclerosis pathogenesis. We determined the effect of salidroside on oxidized
      low-density lipoprotein (ox-LDL)-induced foam cell formation and apoptosis in
      THP1 human acute monocytic leukemia cells and investigated the associated
      molecular mechanisms. METHODS: THP1-derived macrophages were incubated with
      salidroside for 5 h and then exposed to ox-LDL for 24 h to induce foam cell
      formation. Cytotoxicity, lipid deposition, apoptosis, and the expression of
      various proteins were tested using the CCK8 kit, Oil Red O staining, flow
      cytometry, and western blotting, respectively. RESULTS: Ox-LDL treatment alone
      promoted macrophage-derived foam cell formation, while salidroside treatment
      alone inhibited it (p < 0.05). The number of early/late apoptotic cells decreased
      with salidroside treatment in a dose-dependent manner (p < 0.05). Salidroside
      dramatically upregulated nuclear factor erythroid 2-related factor 2, but had no
      effect on heme oxygenase-1 expression; moreover, it markedly downregulated ox-LDL
      receptor 1 and upregulated ATP-binding cassette transporter A1. Salidroside also
      obviously decreased the phosphorylation of JNK, ERK, p38 MAPK, and increased that
      of Akt. However, the total expression of these proteins was not affected.
      CONCLUSION: Based on our findings, we speculate that salidroside can suppress ox
      LDL-induced THP1-derived foam cell formation and apoptosis, partly by regulating
      the MAPK and Akt signaling pathways.

PMID- 29017560
TI  - Effect of intra-pregnancy nonsurgical periodontal therapy on inflammatory
      biomarkers and adverse pregnancy outcomes: a systematic review with meta
      analysis.
AB  - BACKGROUND: The aim of this systematic review with meta-analysis was to analyze
      the effects of intra-pregnancy nonsurgical periodontal therapy on periodontal
      inflammatory biomarkers and adverse pregnancy outcomes. METHODS: On June 5, 2017,
      we searched PubMed, Cochrane, SCOPUS, Web of Science, LILACS, ProQuest, Open
      Grey, and Google Scholar databases. Randomized clinical trials in which pregnant
      women with chronic periodontitis underwent nonsurgical periodontal therapy,
      compared with an untreated group, tested for inflammatory biomarkers, and
      followed till delivery were included. Primary outcomes were preterm birth, low
      birth weight, and preeclampsia. Meta-analysis was performed with 5.3.5 version of
      Review Manager software. RESULTS: We found 565 references in the databases, 326
      after duplicates removal, 28 met criteria for full text reading, and 4 met
      eligibility criteria for quantitative and qualitative synthesis. Intra-pregnancy
      nonsurgical periodontal therapy improved periodontal clinical parameters
      (periodontal pocket depth, clinical attachment level, and bleeding on probing)
      and reduced biomarker level from gingival crevicular fluid (GCF), and some from
      blood serum; however, it did not influence biomarker level from umbilical cord
      blood. Meta-analysis showed tendency for reduction of the risk of preterm birth
      before 37 weeks for treated group (risk ratio (RR) = 0.54, 95% CI 0.38-0.77; p =
      0.0007; inconsistency indexes (I2) 32%) but did not show any difference for low
      birth weight occurrence (RR = 0.78, 95%CI 0.50-1.21; p = 0.27; I2 41%). No
      included study considered preeclampsia as a gestational outcome. CONCLUSIONS:
      These results demonstrated that the intra-pregnancy nonsurgical periodontal
      therapy decreased periodontal inflammatory biomarker levels from gingival
      crevicular fluid and some from serum blood, with no influence on inflammatory
      biomarker level from cord blood, and it did not consistently reduce adverse
      gestational adverse outcome occurrence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42015027750.

PMID- 29017561
TI  - Trial and error: evaluating and refining a community model of HIV testing in
      Australia.
AB  - BACKGROUND: The 2012 regulatory approval of HIV rapid point of care (RPOC) tests
      in Australia and a national strategic focus on HIV testing provided a catalyst
      for implementation of non-clinical HIV testing service models. PRONTO! opened in
      2013 as a two-year trial delivering peer-led community-based HIV RPOC tests
      targeting gay, bisexual and other men who have sex with men (GBM), with the aim
      of increasing HIV testing frequency. Initial data suggested this aim was not
      achieved and, as part of a broader service evaluation, we sought to explore
      client acceptability and barriers to testing at PRONTO! to refine the service
      model. METHODS: We present descriptive and thematic analyses of data from two in
      depth evaluation surveys and four focus groups with PRONTO! clients focused on
      service acceptability, client testing history, intentions to test and barriers to
      testing for HIV and other sexually transmitted infections (STIs). RESULTS: The
      three novel aspects of the PRONTO! model, testing environment, rapid-testing,
      peer-staff, were reported to be highly acceptable among survey and focus group
      participants. Focus group discussions revealed that the PRONTO! model reduced
      anxiety associated with HIV testing and created a comfortable environment
      conducive to discussing sexual risk and health. However, an absence of STI
      testing at PRONTO!, driven by restrictions on medical subsidies for STI testing
      and limited funds available at the service level created a barrier to HIV
      testing. An overwhelming majority of PRONTO! clients reported usually testing for
      STIs alongside HIV and most reported plans to seek STI testing after testing for
      HIV at PRONTO!. When deciding where, when and what to test for, clients reported
      balancing convenience and relative risk and consequences for each infection as
      guiding their decision-making. CONCLUSIONS: A community-based and peer-led HIV
      testing model reduced previously reported barriers to HIV testing, while
      introducing new barriers. The absence of STI testing at PRONTO! and the need to
      access multiple services for comprehensive sexual health screening, created a
      significant service engagement barrier for some clients. Understanding client
      motivations to access testing and ensuring novel service models meet client needs
      is crucial for developing acceptable sexual health services for high-risk
      populations.

PMID- 29017563
TI  - Herceptin(r) (trastuzumab) in HER2-positive early breast cancer: protocol for a
      systematic review and cumulative network meta-analysis.
AB  - BACKGROUND: Human epidermal growth factor receptor 2-positive (HER2+) breast
      cancer is an aggressive disease that makes up about 20% of all invasive breast
      cancers. HER2+ breast cancer is associated with poor prognosis and high mortality
      rates, but the development of HER2-targeted therapies, such as originator
      trastuzumab (Herceptin(r)), has substantially improved patient survival. Numerous
      clinical trials and reviews have investigated the efficacy of HER2-targeted
      therapies over the past few decades; however, no study has specifically
      investigated the vast body of evidence on trastuzumab in comparison to
      chemotherapy regimens, endocrine therapies, and other targeted therapies. This
      systematic review and cumulative network meta-analysis (NMA) will synthesize
      available evidence to evaluate the survival benefit conferred by the addition of
      originator trastuzumab to standard chemotherapy and to compare the most widely
      used trastuzumab regimens in patients with HER2+ early breast cancer, based on
      results from randomized controlled trials (RCTs) and comparative observational
      studies. METHODS/DESIGN: A systematic search of Embase, MEDLINE(r), and the
      Cochrane Library has been designed by an experienced medical information
      specialist and peer reviewed by another senior information specialist. RCTs and
      comparative observational studies of patients with HER2+ early breast cancer
      indexed from 1990 onwards will be eligible for inclusion. Two investigators will
      independently assess studies for inclusion and use standardized data extraction
      templates to collect data on study and patient characteristics. The primary
      outcome of interest is overall survival. Bayesian cumulative NMA methods will be
      used to quantify the evolution of publicly available evidence using both fixed
      and random effects models. DISCUSSION: This study will evaluate survival trends
      associated with originator trastuzumab in patients with HER2+ early breast
      cancer. As originator trastuzumab has been researched in both clinical and real
      world settings for close to 20 years, a cumulative NMA is likely to show improved
      precision around the parameter estimates for trastuzumab now compared with when
      the drug was initially launched in the USA in 1998. A better understanding of the
      evolution of publicly available comparative evidence for originator trastuzumab
      will further inform treatment for patients with HER2+ early breast cancer,
      providing benefit to patients, health professionals, and researchers. SYSTEMATIC
      REVIEW REGISTRATION: PROSPERO CRD42017055763 https://www.crd.york.ac.uk/PROSPERO.

PMID- 29017562
TI  - Contextual tumor suppressor function of T cell death-associated gene 8 (TDAG8) in
      hematological malignancies.
AB  - BACKGROUND: Extracellular acidosis is a condition found within the tumor
      microenvironment due to inadequate blood perfusion, hypoxia, and altered tumor
      cell metabolism. Acidosis has pleiotropic effects on malignant progression;
      therefore it is essential to understand how acidosis exerts its diverse effects.
      TDAG8 is a proton-sensing G-protein-coupled receptor that can be activated by
      extracellular acidosis. METHODS: TDAG8 gene expression was analyzed by
      bioinformatic analyses and quantitative RT-PCR in human hematological
      malignancies. Retroviral transduction was used to restore TDAG8 expression in
      U937, Ramos and other blood cancer cells. Multiple in vitro and in vivo
      tumorigenesis and metastasis assays were employed to evaluate the effects of
      TDAG8 expression on blood cancer progression. Western blotting,
      immunohistochemistry and biochemical approaches were applied to elucidate the
      underlying mechanisms associated with the TDAG8 receptor pathway. RESULTS: TDAG8
      expression is significantly reduced in human blood cancers in comparison to
      normal blood cells. Severe acidosis, pH 6.4, inhibited U937 cancer cell
      proliferation while mild acidosis, pH 6.9, stimulated its proliferation. However,
      restoring TDAG8 gene expression modulated the U937 cell response to mild
      extracellular acidosis and physiological pH by reducing cell proliferation. Tumor
      xenograft experiments further revealed that restoring TDAG8 expression in U937
      and Ramos cancer cells reduced tumor growth. It was also shown U937 cells with
      restored TDAG8 expression attached less to Matrigel, migrated slower toward a
      chemoattractant, and metastasized less in severe combined immunodeficient mice.
      These effects correlated with a reduction in c-myc oncogene expression. The
      mechanistic investigation indicated that Galpha13/Rho signaling arbitrated the
      TDAG8-mediated c-myc oncogene repression in response to acidosis. CONCLUSIONS:
      This study provides data to support the concept that TDAG8 functions as a
      contextual tumor suppressor down-regulated in hematological malignancies and
      potentiation of the TDAG8 receptor pathway may be explored as a potential anti
      tumorigenic approach in blood cancers.

PMID- 29017564
TI  - Factors influencing risky sexual behaviour among Mozambican miners: a socio
      epidemiological contribution for HIV prevention framework in Mozambique.
AB  - BACKGROUND: Information dealing with social and behavioural risk factors as well
      as their mechanisms among Mozambican migrants working in South African mines
      remains undocumented. This study aims to understand the various factors
      influencing HIV-related risk behaviours and the resulting HIV positive status of
      Mozambican miners employed by South African mines. This analysis was undertaken
      in order to inform a broader and more effective HIV preventive framework in
      Mozambique. METHOD: This study relied upon data sourced from the first Integrated
      Biological and Behavioural Survey among Mozambican miners earning their living in
      South African mines. It employs quantitative techniques using standard
      statistical tools to substantiate the laid-down objectives. The primary technique
      applied in this paper is the multivariable statistical method used in the
      formulation and application of a proximate determinants framework. RESULTS: The
      odds of reporting one sexual partner were roughly three times higher for miners
      working as perforators as opposed to other types of occupation. As well, the odds
      of condom use - always or sometimes - for miners in the 31-40 age group were
      three times higher than the odds of condom use in the 51+ age group. Miners with
      lower education levels were less likely to use condoms. The odds of being HIV
      positive when the miner reports use of alcohol or drugs (sometimes/always) is
      0.32 times lower than the odds for those reporting never use of alcohol or drugs.
      And finally, the odds of HIV positive status for those using condoms were 2.16
      times that of miners who never used condoms, controlling for biological and other
      proximate determinants. CONCLUSION: In Mozambique, behavioural theory emphasising
      personal behavioural changes is the main strategy to combat HIV among miners. Our
      findings suggest there is a need to change thinking processes about how to
      influence safer sexual behaviour. This is viewed to be the result of a person's
      individual decision, due to of the complexity of social and contextual factors
      that may also influence sexual behaviours. This only stresses the need for HIV
      prevention strategies to exclusively transcend individual factors while
      considering the broader social and contextual phenomena influencing HIV risk
      among Mozambican miners.

PMID- 29017565
TI  - Safety and efficacy of Qishen granules in patients with chronic heart failure:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Chronic heart failure (CHF), the final stage of various
      cardiovascular diseases, is a major public health problem resulting in
      significant hospitalization rates, mortality, and huge health care costs despite
      advances in the treatment and management of heart failure and heart failure
      related risk factors. Qishen granules (QSG), a Chinese herbal formula, is widely
      used by traditional Chinese medicine (TCM) practitioners to treat CHF. Several
      animal experimental studies have showed that QSG can significantly relieve the
      heart failure symptoms in CHF rat models. However, there is as yet no standard
      clinical trial to confirm this. Thus, the investigators are conducting this study
      to evaluate the efficacy and safety of QSG in a large, and varied population.
      METHODS/DESIGN: This study is designed as a randomized, placebo-controlled, multi
      center, double-blind clinical trial with parallel groups. A total of 200 patients
      with CHF will be recruited and randomly allocated to either the QSG treatment
      group or the placebo group (in a 1:1 ratio). The patients will receive QSG or
      placebo granules twice a day for 12 weeks. The primary outcome is the proportion
      of patients in the QSG group, compared with the placebo group, demonstrating a
      more than 30% decrease in NT-proBNP level during 12 weeks of treatment. The
      secondary outcomes consist of composite cardiac events, New York Heart
      Association functional classification, 6-minute walking distance, left
      ventricular ejection fraction, patient quality of life, and the TCM syndrome
      integral scale. DISCUSSION: On a background of standard treatment, QSG may
      further reduce the levels of NT-proBNP. This trial will provide high-quality
      evidence on the efficacy and safety of QSG in treating CHF, thus providing
      reference for clinical application of QSG. TRIAL REGISTRATION: Clinical
      Trials.gov: NCT03027375 . Registered on 16 January 2017.

PMID- 29017566
TI  - Right ventricular functional analysis utilizing first pass radionuclide
      angiography for pre-operative ventricular assist device planning: a multi
      modality comparison.
AB  - BACKGROUND: Advanced heart failure treated with a left ventricular assist device
      is associated with a higher risk of right heart failure. Many advanced heart
      failures patients are treated with an ICD, a relative contraindication to MRI,
      prior to assist device placement. Given this limitation, left and right
      ventricular function for patients with an ICD is calculated using radionuclide
      angiography utilizing planar multigated acquisition (MUGA) and first pass
      radionuclide angiography (FPRNA), respectively. Given the availability of MRI
      protocols that can accommodate patients with ICDs, we have correlated the
      findings of ventricular functional analysis using radionuclide angiography to
      cardiac MRI, the reference standard for ventricle function calculation, to
      directly correlate calculated ejection fractions between these modalities, and to
      also assess agreement between available echocardiographic and hemodynamic
      parameters of right ventricular function. METHODS: A retrospective review from
      January 2012 through May 2014 was performed to identify advanced heart failure
      patients who underwent both cardiac MRI and radionuclide angiography for
      ventricular functional analysis. Nine heart failure patients (8 men, 1 woman;
      mean age of 57.0 years) were identified. The average time between the cardiac MRI
      and radionuclide angiography exams was 38.9 days (range: 1 - 119 days). All
      patients undergoing cardiac MRI were scanned using an institutionally approved
      protocol for ICD with no device-related complications identified. A retrospective
      chart review of each patient for cardiomyopathy diagnosis, clinical follow-up,
      and echocardiogram and right heart catheterization performed during evaluation
      was also performed. RESULTS: The 9 patients demonstrated a mean left ventricular
      ejection fraction (LVEF) using cardiac MRI of 20.7% (12 - 40%). Mean LVEF using
      MUGA was 22.6% (12 - 49%). The mean right ventricular ejection fraction (RVEF)
      utilizing cardiac MRI was 28.3% (16 - 43%), and the mean RVEF calculated by FPRNA
      was 32.6% (9 - 56%). The mean discrepancy for LVEF between cardiac MRI and MUGA
      was 4.1% (0 - 9%), and correlation of calculated LVEF using cardiac MRI and MUGA
      demonstrated an R of 0.9. The mean discrepancy for RVEF between cardiac MRI and
      FPRNA was 12.0% (range: 2 - 24%) with a moderate correlation (R = 0.5). The
      increased discrepancies for RV analysis were statistically significant using an
      unpaired t-test (t = 3.19, p = 0.0061). Echocardiogram parameters of RV function,
      including TAPSE and FAC, were for available for all 9 patients and agreement with
      cardiac MRI demonstrated a kappa statistic for TAPSE of 0.39 (95% CI of 0.06 -
      0.72) and for FAC of 0.64 (95% of 0.21 - 1.00). CONCLUSION: Heart failure
      patients are increasingly requiring left ventricular assist device placement;
      however, definitive evaluation of biventricular function is required due to the
      increased mortality rate associated with right heart failure after assist device
      placement. Our results suggest that FPRNA only has a moderate correlation with
      reference standard RVEFs calculated using cardiac MRI, which was similar to
      calculated agreements between cardiac MRI and echocardiographic parameters of
      right ventricular function. Given the need for identification of patients at risk
      for right heart failure, further studies are warranted to determine a more
      accurate estimate of RVEF for heart failure patients during pre-operative
      ventricular assist device planning.

PMID- 29017569
TI  - Impact of severe left ventricular dysfunction on in-hospital and mid-term
      outcomes of Chinese patients undergoing first isolated off-pump coronary artery
      bypass grafting.
AB  - BACKGROUND: Few studies focused on evaluating the impacts of preoperative severe
      left ventricular dysfunction on clinical outcomes of patients undergoing off-pump
      coronary artery bypass grafting surgery (OPCAB). This single center retrospective
      study aimed to evaluate the impacts of severe left ventricular dysfunction on in
      hospital and mid-term clinical outcomes of Chinese patients undergoing first,
      scheduled, and isolated OPCAB surgery. METHODS: From January 2010 to December
      2014, 2032 eligible patients were included in this study and were divided into 3
      groups: a severe group (patients with preoperative left ventricular ejection
      fraction (LVEF) of <=35%, n = 128), an impaired group (patients with preoperative
      LVEF of 36-50%, n = 680), and a normal group (patients with preoperative LVEF of
      >50%, n = 1224). In-hospital and follow-up clinical outcomes were investigated
      and compared. RESULTS: Patients in the severe group compared to the other 2
      groups had higher in-hospital mortality and higher incidences of low cardiac
      output and prolonged ventilation. Kaplan-Meier curves showed a similar cumulative
      follow-up survival between the severe group and the impaired group (chi2 = 1.980,
      Log-rank p = 0.159) and between the severe group and the normal group (chi2 =
      2.701, Log-rank p = 0.102). Multivariate Cox regression indicated that grouping
      was not a significant variable related to mid-term all-cause mortality. No
      significant difference was found in the rate of repeat revascularization between
      the severe group (2.4%) and the other 2 groups. CONCLUSIONS: Patients with
      preoperative LVEF of <=35% compared to preoperative LVEF of >35% increased the
      risk of in-hospital death and incidences of postoperative low cardiac output and
      prolonged ventilation, but shared similar mid-term all-cause mortality and repeat
      revascularization after OPCAB surgery.

PMID- 29017567
TI  - Impairment of IGF2 gene expression in prostate cancer is triggered by epigenetic
      dysregulation of IGF2-DMR0 and its interaction with KLF4.
AB  - BACKGROUND: Human cancer cells often exhibit impaired IGF2 expression and the
      underlying mechanisms are multifaceted and complex. Besides the well-known
      imprinting control region IGF2/H19-ICR, the involvement of a differentially
      methylated region in the promoter P0 of IGF2 gene (IGF2-DMR0) has been suggested.
      Here, we evaluate several mechanisms potentially leading to up- and/or down
      regulation of IGF2 expression in prostate cancer and present a novel role of
      Kruppel-like factor 4 (KLF4) as a transcriptional regulator of IGF2 binding in
      IGF2-DMR0. METHODS: Putative binding sites for transcription factors were
      identified in IGF2-DMR0 using JASPAR CORE database. Gene expressions were
      analyzed by RT-qPCR in prostate carcinoma and adjacent benign prostate
      hyperplasia samples obtained by radical prostatectomy (86 RP-PCa and 47 RP-BPH)
      and BPH obtained by transurethral prostate resection (13 TUR-BPH). Pyrosequencing
      and qMSP were used for DNA methylation studies in IGF2-DMR0, IGF2/H19-ICR and
      Glutathione-S-transferase-P1 (GSTP1) promoter. Loss of imprinting (LOI) was
      analyzed by RFLP. Copy number variation (CNV) test was performed using qBiomarker
      CNV PCR Assay. KLF4-binding and histone-modifications were analyzed by ChIP-qPCR
      in prostate cancer cell lines exhibiting differentially methylated IGF2-DMR0
      (LNCaP hypomethylated and DU145 hypermethylated). KLF4 protein was analyzed by
      western blot. Statistical associations of gene expression to methylation, IGF2
      LOI and CNV were calculated by Mann-Whitney-U-test. Correlations between gene
      expression and methylation levels were evaluated by Spearman's-Rank-Correlation
      test. RESULTS: We found a significant reduction of IGF2 expression in the
      majority of RP-PCa and RP-BPH in comparison to TUR-BPH. Analyzing potential
      molecular reasons, we found in RP-PCa and RP-BPH in comparison to TUR-BPH a
      significant hypomethylation of IGF2-DMR0, which coincided with hypermethylation
      of GSTP1-promoter, a prominent marker of prostate tumors. In contrast, IGF2 LOI
      and CNV did not associate significantly with up- and/or down-regulation of IGF2
      expression in prostate tumors. By analyzing IGF2-DMR0, we detected a consensus
      sequence for KLF4 with a z-score of 7.6. Interestingly, we found that KLF4 binds
      to hypomethylated (17%) IGF2-DMR0 enriched with H3K9me3 and H3K27me3 (LNCaP), but
      does not bind under hypermethylated (85%) and H3K4me3-enriched conditions
      (DU145). KLF4 expression was detected in TUR-BPH as well as in RP-BPH and RP-PCa
      and showed a highly significant correlation to IGF2 expression. CONCLUSIONS: Our
      study demonstrated that in human prostate cancer the impairment of IGF2
      expression is accompanied by hypomethylation of IGF2-DMR0. We revealed that KLF4
      is a putative transcriptional regulator of IGF2, which binds in IGF2-DMR0 in
      dependence of the prevailing epigenetic state in this region. Herewith we provide
      complementary new insights into IGF2 dysregulation mechanisms as a critical
      process in prostate tumorigenesis.

PMID- 29017570
TI  - Development of a short scale for assessing economic environmental aspects in
      patients with spinal diseases using Rasch analysis.
AB  - BACKGROUND: Economic environmental factors represent important barriers to
      participation and have deleterious effects on quality of life (QOL) in persons
      with spinal diseases (SpD). While economic factors are anchored in the
      International Classification of Functioning, Disability and Health, their
      influence on QOL and participation from patients' perspectives is an infrequent
      focus of research. The aim of the present research is to calibrate a culturally
      adapted Rasch-based questionnaire assessing economic QOL in patients with SpD.
      METHODS: The 11-items of the German economic-QOL-scale were answered by 325
      patients with SpD on a four-point Likert-scale. Fit to the Rasch measurement
      model was investigated by testing for stochastic ordering of the items,
      unidimensionality, local independence, and differential item functioning (DIF).
      RESULTS: After adjusting for local dependency, fit to the Rasch model was
      achieved with a non-significant item-trait interaction (chi-squaredf = 20 = 34.8,
      p = 0.021). The person separation reliability equaled 0.88, the scale was free
      from age- or gender-related DIF, and unidimensionality could be verified.
      CONCLUSIONS: The Rasch-based German version of the economic-QOL-scale represents
      a suitable instrument to investigate the influences of economic factors on
      patients' QOL at a group and individual level. It can be easily applied in
      research and practice and may be administered quickly in combination with other
      instruments. The short test duration implies a low test burden for patients and a
      minimum of time expenditure by clinicians when evaluating the results.

PMID- 29017568
TI  - Polychlorinated biphenyls and depression: cross-sectional and longitudinal
      investigation of a dopamine-related Neurochemical path in the German HELPcB
      surveillance program.
AB  - BACKGROUND: Exposure to polychlorinated biphenyls (PCBs) is associated with
      depressive symptomatology. A cause of depressive symptoms is a disturbance in the
      neurotransmitter system of dopamine (DA). Animal as well as human studies report
      that PCBs can influence the DA system. This study examined whether PCB-related
      depressive symptoms are affected by DA metabolites in humans with high PCB body
      burden. METHODS: This study is part of the German HELPcB surveillance program
      (Health Effects in high Level exposure to PCB) for occupationally exposed workers
      and their relatives. Data was collected from 178 participants on two measurement
      time points (t1 and t2) with a one-year time lag in between the two time points.
      PCBs were analyzed in plasma via human biomonitoring and a validated
      questionnaire was used to identify existence and severity of depressive symptoms.
      As a surrogate for DA, we measured its metabolites homovanillic acid (HVA) and
      vanillylmandelic acid (VMA) in urine. Mediation analyses were performed to test
      whether the association between PCB exposure and severity of depressive symptoms
      is mediated by urinary concentration of DA metabolites HVA and VMA. The mediation
      was tested with the SPSS macro MEDIATE. RESULTS: We found a significant mediation
      over time for lower-chlorinated, higher-chlorinated and dioxin-like PCBs. The
      positive association between PCB exposure with severity of depressive symptoms
      was mediated by the main DA metabolite HVA. At t1 a higher exposure with PCBs was
      associated with lower concentration in urinary HVA. A reduced HVA concentration
      at t1 was correlated with increased depressive symptoms severity at t2. No
      meditations were found for VMA. CONCLUSIONS: This work indicates that the
      association of PCB exposure and an increase of depressive symptoms after one year
      is mediated by the DA metabolite HVA as a surrogate for DA. These are first steps
      towards finding an explanation for an underlying neurochemical pathomechanism of
      PCB-related depressive symptomatology.

PMID- 29017572
TI  - Temporal genetic differentiation in Glossina pallidipes tsetse fly populations in
      Kenya.
AB  - BACKGROUND: Glossina pallidipes is a major vector of both Human and Animal
      African Trypanosomiasis (HAT and AAT) in Kenya. The disease imposes economic
      burden on endemic regions in Kenya, including south-western Kenya, which has
      undergone intense but unsuccessful tsetse fly control measures. We genotyped 387
      G. pallidipes flies at 13 microsatellite markers to evaluate levels of temporal
      genetic variation in two regions that have been subjected to intensive
      eradication campaigns from the 1960s to the 1980s. One of the regions, Nguruman
      Escarpment, has been subject to habitat alteration due to human activities, while
      the other, Ruma National Park, has not. In addition, Nguruman Escarpment is
      impacted by the movement of grazing animals into the area from neighboring
      regions during the drought season. We collected our samples from three
      geographically close sampling sites for each of the two regions. Samples were
      collected between the years 2003 and 2015, spanning ~96 tsetse fly generations.
      RESULTS: We established that allelic richness averaged 3.49 and 3.63, and
      temporal Ne estimates averaged 594 in Nguruman Escarpment and 1120 in Ruma
      National Park. This suggests that genetic diversity is similar to what was found
      in previous studies of G. pallidipes in Uganda and Kenya, implying that we could
      not detect a reduction in genetic diversity following the extensive control
      efforts during the 1960s to the 1980s. However, we did find differences in
      temporal patterns of genetic variation between the two regions, indicated by
      clustering analysis, pairwise FST, and Fisher's exact tests for changes in allele
      and genotype frequencies. In Nguruman Escarpment, findings indicated
      differentiation among samples collected in different years, and evidence of local
      genetic bottlenecks in two locations previous to 2003, and between 2009 and 2015.
      In contrast, there was no consistent evidence of differentiation among samples
      collected in different years, and no evidence of local genetic bottlenecks in
      Ruma National Park. CONCLUSION: Our findings suggest that, despite extensive
      control measures especially between the 1960s and the 1980s, tsetse flies in
      these regions persist with levels of genetic diversity similar to that found in
      populations that did not experience extensive control measures. Our findings also
      indicate temporal genetic differentiation in Nguruman Escarpment detected at a
      scale of > 80 generations, and no similar temporal differentiation in Ruma
      National Park. The different level of temporal differentiation between the two
      regions indicates that genetic drift is stronger in Nugruman Escarpment, for as
      yet unknown reasons, which may include differences in land management. This
      suggests land management may have an impact on G. pallidipes population genetics,
      and reinforces the importance of long term monitoring of vector populations in
      estimates of parameters needed to model and plan effective species-specific
      control measures.

PMID- 29017571
TI  - DNA damage response and cancer therapeutics through the lens of the Fanconi
      Anemia DNA repair pathway.
AB  - Fanconi Anemia (FA) is a rare, inherited genomic instability disorder, caused by
      mutations in genes involved in the repair of interstrand DNA crosslinks (ICLs).
      The FA signaling network contains a unique nuclear protein complex that mediates
      the monoubiquitylation of the FANCD2 and FANCI heterodimer, and coordinates
      activities of the downstream DNA repair pathway including nucleotide excision
      repair, translesion synthesis, and homologous recombination. FA proteins act at
      different steps of ICL repair in sensing, recognition and processing of DNA
      lesions. The multi-protein network is tightly regulated by complex mechanisms,
      such as ubiquitination, phosphorylation, and degradation signals that are
      critical for the maintenance of genome integrity and suppressing tumorigenesis.
      Here, we discuss recent advances in our understanding of how the FA proteins
      participate in ICL repair and regulation of the FA signaling network that assures
      the safeguard of the genome. We further discuss the potential application of
      designing small molecule inhibitors that inhibit the FA pathway and are synthetic
      lethal with DNA repair enzymes that can be used for cancer therapeutics.

PMID- 29017573
TI  - Gad67 haploinsufficiency reduces amyloid pathology and rescues olfactory memory
      deficits in a mouse model of Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is the most common age-related
      neurodegenerative disorder, affecting millions of people worldwide. Although
      dysfunction of multiple neurotransmitter systems including cholinergic,
      glutamatergic and GABAergic systems has been associated with AD progression the
      underlying mechanisms remain elusive. We and others have recently found that GABA
      content is elevated in AD brains and linked to cognitive deficits in AD mouse
      models. The glutamic acid decarboxylase 67 (GAD67) is the major enzyme converting
      glutamate into GABA and has been implied in a number of neurological disorders
      such as epilepsy and schizophrenia. However, whether Gad67 is involved in AD
      pathology has not been well studied. Here, we investigate the functional role of
      GAD67 in an AD mouse model with Gad67 haploinsufficiency that is caused by
      replacing one allele of Gad67 with green fluorescent protein (GFP) gene during
      generation of GAD67-GFP mice. METHODS: To genetically reduce GAD67 in AD mouse
      brains, we crossed the Gad67 haploinsufficient mice (GAD67-GFP+/-) with 5xFAD
      mice (harboring 5 human familial AD mutations in APP and PS1 genes) to generate a
      new line of bigenic mice. Immunostaining, ELISA, electrophysiology and behavior
      test were applied to compare the difference between groups. RESULTS: We found
      that reduction of GAD67 resulted in a significant decrease of amyloid beta
      production in 5xFAD mice. Concurrently, the abnormal astrocytic GABA and tonic
      GABA currents, as well as the microglial reactivity were significantly reduced in
      the 5xFAD mice with Gad67 haploinsufficiency. Importantly, the olfactory memory
      deficit of 5xFAD mice was rescued by Gad67 haploinsufficiency. CONCLUSIONS: Our
      results demonstrate that GAD67 plays an important role in AD pathology,
      suggesting that GAD67 may be a potential drug target for modulating the progress
      of AD.

PMID- 29017574
TI  - Recommendations for reporting of systematic reviews and meta-analyses of
      diagnostic test accuracy: a systematic review.
AB  - BACKGROUND: This study is to perform a systematic review of existing guidance on
      quality of reporting and methodology for systematic reviews of diagnostic test
      accuracy (DTA) in order to compile a list of potential items that might be
      included in a reporting guideline for such reviews: Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy (PRISMA-DTA).
      METHODS: Study protocol published on EQUATOR website. Articles in full text or
      abstract form that reported on any aspect of reporting systematic reviews of
      diagnostic test accuracy were eligible for inclusion. We used the Ovid platform
      to search Ovid MEDLINE(r), Ovid MEDLINE(r) In-Process & Other Non-Indexed
      Citations and Embase Classic+Embase through May 5, 2016. The Cochrane Methodology
      Register in the Cochrane Library (Wiley version) was also searched. Title and
      abstract screening followed by full-text screening of all search results was
      performed independently by two investigators. Guideline organization websites,
      published guidance statements, and the Cochrane Handbook for Diagnostic Test
      Accuracy were also searched. Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses (PRISMA) and Standards for Reporting Diagnostic Accuracy (STARD)
      were assessed independently by two investigators for relevant items. RESULTS: The
      literature searched yielded 6967 results; 386 were included after title and
      abstract screening and 203 after full-text screening. After reviewing the
      existing literature and guidance documents, a preliminary list of 64 items was
      compiled into the following categories: title (three items); introduction (two
      items); methods (35 items); results (13 items); discussion (nine items), and
      disclosure (two items). CONCLUSION: Items on the methods and reporting of DTA
      systematic reviews in the present systematic review will provide a basis for
      generating a PRISMA extension for DTA systematic reviews.

PMID- 29017575
TI  - Evidence for viable and stable triploid Trypanosoma congolense parasites.
AB  - BACKGROUND: Recent whole genome sequencing (WGS) analysis identified a viable
      triploid strain of Trypanosoma congolense. This triploid strain BANANCL2 was a
      clone of the field isolate BANAN/83/CRTRA/64 that was collected from cattle in
      Burkina Faso in 1983. RESULTS: We demonstrated the viability and stability of
      triploidy throughout the complete life-cycle of the parasite by infecting tsetse
      flies with the triploid clone BANANCL2. Proboscis-positive tsetse flies
      efficiently transmitted the parasites to mice resulting in systemic infections.
      WGS of the parasites was performed at all life-cycle stages, and a method based
      on a block alternative allele frequency spectrum was developed to efficiently
      detect the ploidy profiles of samples with low read depth. This approach
      confirmed the triploid profile of parasites throughout their life-cycle in the
      tsetse fly and the mammalian host, demonstrating that triploidy is present at all
      stages and is stable over time. CONCLUSION: The presence of viable field-isolated
      triploid parasites indicates another possible layer of genetic diversity in
      natural T. congolense populations. The comparison between triploid and diploid
      parasites provides a unique model system to study the impact of chromosome copy
      number variations in African trypanosomes. In addition, the consequences of
      triploidy can be further investigated using this stable triploid model.

PMID- 29017576
TI  - Traditional knowledge hiding in plain sight - twenty-first century ethnobotany of
      the Chacobo in Beni, Bolivia.
AB  - BACKGROUND: The Chacobo are a Panoan speaking tribe of about 1000 members (300+
      adults) in Beni, Bolivia. Originally nomadic, the Chacabo were relocated to their
      current main location in the 1960s. Researchers have visited the Chacabo since
      1911. A first more detailed anthropological report exists from the late 1960s,
      and ecological-ethnobotanical studies were conducted in the 1980s and 1990s. The
      presented work represents a complete ethnobotanical inventory of the entire adult
      Chacobo population, with interviews and plant collection conducted directly by
      Chacobo counterparts. METHODS: Based on previous reports and our preliminary
      studies, we hypothesized that twenty-first century Chacobo plant use centered on
      income generation, and that traditional plant use related to household utensils,
      medicine and traditional crop varieties had almost disappeared. To test this
      hypothesis, we started the "Chacobo Ethnobotany Project," training 10 indigenous
      Chacobo participants in ethnobotanical interview and plant collection techniques,
      in order to more fully document Chacobo knowledge and avoid the influence of
      foreign interviewers. RESULTS: Our study found 331 useful plant species in
      241genera of 95 plant families, with leaves, roots and bark being the most
      commonly used plant parts The comprehensive documentation that these methods
      enabled completely nullified our initial hypothesis of knowledge loss.
      Traditional crop varieties are still widely grown and traditional knowledge is
      alive. Moreover, it is being actively recuperated in certain domains by the
      younger generation. Most Chacobo know, and can name, traditional utensils and
      tools, although only the older generation has still the skills to manufacture
      them. While many Chacobo still know the names and uses of medicinal species, the
      younger generation is however often unsure how to identify them. CONCLUSIONS: In
      this paper we illustrate the complexity of perspectives on knowledge at different
      ages, and the persistence of knowledge over almost a century. We found that
      traditional knowledge was only partially affected by the processes of exposure to
      a market economy, and that different knowledge domains experienced different
      trends as a result of these changes. Overall knowledge was widely distributed,
      and we did not observe a directional knowledge loss. We stress the importance to
      not directly conclude processes of knowledge loss, cultural erosion or
      acculturation when comparing the knowledge of different age groups.

PMID- 29017577
TI  - Elevated expression of Par3 promotes prostate cancer metastasis by forming a
      Par3/aPKC/KIBRA complex and inactivating the hippo pathway.
AB  - BACKGROUND: Prostate cancer (PCa) is one of the most frequent tumors and leading
      cause of cancer deaths among males worldwide. The majority of deaths are due to
      recurrence and subsequent development of the metastatic cancer. Although loss or
      dislocalization of polarity proteins has been implicated in embryogenesis
      deficiency and tumorigenesis, association of polarity protein expression levels
      with tumor metastasis remains unclear. METHODS: Bioinformatics, qRT-PCR, western
      blot and immunohistochemical (IHC) analyses were used to examine expression of
      Par3, a key component of polarity-associated partitioning defective (PAR)
      complex, in primary and metastatic clinical PCa samples. Loss-of-function and
      gain-of-function studies in vitro and in vivo were performed to determine the
      functions of Par3 during metastasis of PCa. Co-immunoprecipitation (co-IP),
      western blot, immunofluorescence (IF), chromatin immunoprecipitation (ChIP) and
      qRT-PCR analyses were conducted to investigate the underlying mechanism for the
      function of Par3 on PCa metastasis. RESULTS: In this study, we found that
      elevated expression of Par3 is positively associated with PCa metastasis.
      Knockdown of Par3 inhibits PCa cell migration and invasion in vitro and tumor
      metastasis in vivo, whereas overexpression of Par3 yields the opposite results.
      Mechanistically, Par3 suppresses phosphorylation of LATS to inactivate the Hippo
      pathway and enhances nuclear translocation of YAP by sequestrating KIBRA from the
      KIBRA/Merlin/FRMD6 complex and forming a Par3/aPKC/KIBRA complex. Stable
      knockdown of Par3 leads to restoration of the KIBRA/Merlin/FRMD6 complex and
      activation of the Hippo pathway, and then results in an inhibition on YAP nuclear
      translocation. In addition, in conjunction with the TEA domain (TEAD)
      transcription factor family, intranuclear YAP promotes the transcription of
      several pro-metastatic genes such as the matrix metalloproteinase (MMP) family,
      Zeb1, Snail1 and Twist1. Moreover, knockdown of Par3 downregulates expression of
      these pro-metastatic genes. CONCLUSIONS: Our findings indicate that elevated
      expression of Par3 promotes PCa metastasis via KIBRA sequestration-mediated
      inactivation of the Hippo pathway to upregulate expression of pro-metastatic
      genes. Downregulation of Par3 expression may serve as a potential treatment
      approach for PCa metastasis by activating the Hippo pathway.

PMID- 29017579
TI  - Surveillance of Ixodes ricinus ticks (Acari: Ixodidae) in Iceland.
AB  - BACKGROUND: Ixodes ricinus is a three-host tick, a principal vector of Borrelia
      burgdorferi (s.l.) and one of the main vectors of tick-borne encephalitis (TBE)
      virus. Iceland is located in the North Atlantic Ocean with subpolar oceanic
      climate. During the past 3-4 decades, average temperature has increased,
      supporting more favourable conditions for ticks. Reports of I. ricinus have
      increased in recent years. If these ticks were able to establish in a changing
      climate, Iceland may face new threats posed by tick-borne diseases. METHODS:
      Active field surveillance by tick flagging was conducted at 111 sites around
      Iceland from August 2015 to September 2016. Longworth mammal traps were used to
      trap Apodemus sylvaticus in southwestern and southern Iceland. Surveillance on
      tick importation by migratory birds was conducted in southeastern Iceland, using
      bird nets and a Heligoland trap. Vulpes lagopus carcasses from all regions of the
      country were inspected for ticks. In addition, existing and new passive
      surveillance data from two institutes have been merged and are presented.
      Continental probability of presence models were produced. Boosted Regression
      Trees spatial modelling methods and its predictions were assessed against
      reported presence. RESULTS: By field sampling 26 questing I. ricinus ticks (7
      males, 3 females and 16 nymphs) were collected from vegetation from three
      locations in southern and southeastern Iceland. Four ticks were found on
      migratory birds at their arrival in May 2016. A total of 52 A. sylvaticus were
      live-trapped but no ticks were found nor on 315 V. lagopus carcasses. Passive
      surveillance data collected since 1976, reports further 214 I. ricinus ticks from
      202 records, with an increase of submissions in recent years. The continental
      probability of presence model correctly predicts approximately 75% of the
      recorded presences, but fails to predict a fairly specific category of recorded
      presence in areas where the records are probably opportunistic and not likely to
      lead to establishment. CONCLUSIONS: To the best of our knowledge, this study
      represents the first finding of questing I. ricinus ticks in Iceland. The species
      could possibly be established locally in Iceland in low abundance, although no
      questing larvae have yet been detected to confirm established populations.
      Submitted tick records have increased recently, which may reflect an increase in
      exposure, or in interest in ticks. Furthermore, the amount of records on dogs,
      cats and humans indicate that ticks were acquired locally, presenting a local
      biting risk. Tick findings on migratory birds highlight a possible route of
      importation. Obtaining questing larvae is now a priority to confirm that I.
      ricinus populations are established in Iceland. Further surveys on wild mammals
      (e.g. Rangifer tarandus), livestock and migratory birds are recommended to better
      understand their role as potential hosts for I. ricinus.

PMID- 29017578
TI  - Family Integrated Care (FICare) in Level II Neonatal Intensive Care Units: study
      protocol for a cluster randomized controlled trial.
AB  - BACKGROUND: Every year, about 15 million of the world's infants are born preterm
      (before 37 weeks gestation). In Alberta, the preterm birth rate was 8.7% in 2015,
      the second highest among Canadian provinces. Approximately 20% of preterm infants
      are born before 32 weeks gestation (early preterm), and require care in a Level
      III neonatal intensive care unit (NICU); 80% are born moderate (32 weeks and zero
      days [320/7] to 336/7 weeks) and late preterm (340/7 to 366/7 weeks), and require
      care in a Level II NICU. Preterm birth and experiences in the NICU disrupt early
      parent-infant relationships and induce parental psychosocial distress. Family
      Integrated Care (FICare) shows promise as a model of care in Level III NICUs. The
      purpose of this study is to evaluate length of stay, infant and maternal clinical
      outcomes, and costs following adaptation and implementation of FICare in Level II
      NICUs. METHODS: We will conduct a pragmatic, cluster randomized controlled trial
      (cRCT) in ten Alberta Level II NICUs allocated to one of two groups: FICare or
      standard care. The FICare Alberta model involves three theoretically-based,
      standardized components: information sharing, parenting education, and family
      support. Our sample size of 181 mother-infant dyads per group is based on the
      primary outcome of NICU length of stay, 80% participation, and 80% retention at
      follow-up. Secondary outcomes (e.g., infant clinical outcomes and maternal
      psychosocial distress) will be assessed shortly after admission to NICU, at
      discharge and 2 months corrected age. We will conduct economic analysis from two
      perspectives: the public healthcare payer and society. To understand the utility,
      acceptability, and impact of FICare, qualitative interviews will be conducted
      with a subset of mothers at the 2-month follow-up, and with hospital
      administrators and healthcare providers near the end of the study. DISCUSSION:
      Results of this pragmatic cRCT of FICare in Alberta Level II NICUs will inform
      policy decisions by providing evidence about the clinical effectiveness and costs
      of FICare. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02879799 . Registered
      on 27 May 2016. Protocol version: 9 June 2016; version 2.

PMID- 29017580
TI  - A retrospective analysis of the InterTan nail and proximal femoral nail anti
      rotation in the treatment of intertrochanteric fractures in elderly patients with
      osteoporosis: a minimum follow-up of 3 years.
AB  - BACKGROUND: The study aims to compare the long-term functional and radiographic
      outcomes of two devices for the treatment of primary intertrochanteric fractures
      (IFs, OTA 3.1A2.1-A2.3) in elderly patients with osteoporosis. METHODS: Between
      December 2010 and August 2014, 332 elderly osteoporosis patients with IFs (OTA
      3.1A2.1-A2.3) fixed by an InterTAN nail (IT) or a proximal femoral nail anti
      rotation (PFNA) device were retrospectively evaluated. Follow-up occurred 1, 3,
      6, and 12 months postoperatively and every year thereafter. Mortality was
      recorded. Patient-related functional and radiographic outcomes were compared. The
      primary endpoint was the long-term radiographic outcomes. The secondary endpoint
      was the long-term functional outcomes. RESULTS: A total of 283 patients (283
      hips) with osteoporosis (IT, n = 144; PFNA, n = 139) were evaluated with a mean
      follow-up period of 38.8 months (range, 36-43 months). No between-group
      significant differences were noted in the patient demographics, operation
      variables, and postoperative Harris Hip Score. More radiographic complications
      were noted in terms of screw cut-out, femoral shaft fracture distal or around the
      tip of the main nail, and varus collapse of the femoral head in the PFNA group
      compared with that in the IT group (P < 0.05). CONCLUSION: For osteoporotic IFs
      (OTA 3.1A2.1-A2.3) in elderly patients, the use of IT aids in decreasing
      radiographic complications, but the between-group functional outcomes showed no
      significant difference.

PMID- 29017582
TI  - Differential susceptibility of bovine caruncular and trophoblast cell lines to
      infection with high and low virulence isolates of Neospora caninum.
AB  - BACKGROUND: Neospora caninum, one of the main causes of abortion in cattle, is
      very effective at crossing the placental barrier and placental damage is crucial
      in the pathogenesis of abortion. Bovine trophoblast and caruncular cell layers
      are key cellular components in the maternal-foetal interface in placentomes,
      playing a fundamental role in placental functionality. METHODS: We studied
      tachyzoite adhesion, invasion, proliferation and egress of high- (Nc-Spain7) and
      low- (Nc-Spain1H) virulence N. caninum isolates in established cultures of bovine
      caruncular epithelial (BCEC-1) and trophoblast (F3) cells. The parasite invasion
      rate (pInvR) and the cell infection rate (cInfR) were determined by
      immunostaining plaque assay at different time points and multiplicities of
      infection (MOIs), respectively. In addition, tachyzoite growth kinetics were
      investigated using real-time PCR (qPCR) analysis and immunostaining plaque assay
      at different times. RESULTS: Neospora caninum invaded and proliferated in both
      cell lines. The pInvR was higher in F3 compared to BCEC-1 cells for the Nc-Spain7
      isolate (P < 0.05), and higher for the Nc-Spain7 than the Nc-Spain1H in F3 cells
      (P < 0.01). The cInfR was also higher in F3 cells than in BCEC-1 cells for both
      isolates (P < 0.0001), and the cInfR for the Nc-Spain7 isolate was higher than
      for the Nc-Spain1H isolate in both cell lines (P < 0.05). Tachyzoite growth
      kinetics showed tachyzoite exponential growth until egress at 58 hpi for both
      isolates in F3, whereas Nc-Spain1H showed a non-exponential growth pattern in
      BCEC-1. Asynchronous egress of both isolates was observed from 22 h post
      infection onwards in BCEC-1. In addition, the tachyzoite yield (TY58h) was higher
      in F3 than in BCEC-1 infected by both isolates (P < 0.0001), highlighting better
      replication abilities of both parasites in F3. Nc-Spain7 showed shorter doubling
      times and higher TY58h compared to Nc-Spain1H in F3 cells; adhesion, invasion and
      proliferation mechanisms were very similar for both isolates in BCEC-1.
      CONCLUSIONS: Our results indicate a highly similar behavior of high- and low
      virulence isolates in their interactions with maternal caruncular cells and
      suggest an important role of foetal trophoblasts in the pathogenesis of N.
      caninum infection.

PMID- 29017583
TI  - Mapping freshwater snails in north-western Angola: distribution, identity and
      molecular diversity of medically important taxa.
AB  - BACKGROUND: This study was designed to determine the distribution and identity of
      potential intermediate snail hosts of Schistosoma spp. in Bengo, Luanda, Kwanza
      Norte and Malanje Provinces in north-western Angola. This is an area where
      infection with Schistosoma haematobium, causing urogenital schistosomiasis, is
      common but little is yet known about transmission of the disease. Angola has had
      a varied past with regard to disease control and is revitalising efforts to
      combat neglected tropical diseases. METHODS: Snails were sampled from 60 water
      contact points. Specimens of the genera Bulinus, Biomphalaria or Lymnaea were
      screened for trematode infections by inducing cercarial shedding. Snails were
      initially identified using shell morphology; subsequently a cytochrome c oxidase
      subunit 1 (cox1) gene fragment was amplified from a subset of snails from each
      site, for molecular identification. Cercariae were captured onto FTA cards for
      molecular analysis. Specimens of Bulinus angolensis collected from the original
      locality of the type specimen have been characterised and comparisons made with
      snails collected in 1957 held at the Natural History Museum, London, UK. RESULTS:
      In total snails of nine genera were identified using morphological
      characteristics: Biomphalaria, Bulinus, Gyraulus, Lanistes, Lentorbis, Lymnaea,
      Melanoides, Physa and Succinea. Significant for schistosomiasis transmission, was
      the discovery of Bulinus globosus, B. canescens, B. angolensis, B. crystallinus
      and Biomphalaria salinarum in their type-localities and elsewhere. Bulinus
      globosus and B. angolensis occurred in two distinct geographical areas. The cox1
      sequence for B. globosus differed markedly from those from specimens of this
      species collected from other countries. Bulinus angolensis is more closely
      related to B. globosus than originally documented and should be included in the
      B. africanus group. Schistosoma haematobium cercariae were recovered from B.
      globosus from two locations: Cabungo, Bengo (20 snails) and Calandula, Malanje (5
      snails). Schistosoma haematobium cercariae were identified as group 1 cox1
      corresponding to the type common throughout the African mainland. CONCLUSIONS:
      Various freshwater bodies in north-western Angola harbour potential intermediate
      snail hosts for urogenital schistosomiasis, highlighting the need to map the rest
      of the country to identify areas where transmission can occur and where control
      efforts should be targeted. The molecular phylogeny generated from the samples
      confirmed that considerable variation exists in B. globosus, which is the primary
      snail host for S. haematobium in many regions of Africa.

PMID- 29017581
TI  - Neoadjuvant treatment of pancreatic adenocarcinoma: a systematic review and meta
      analysis of 5520 patients.
AB  - BACKGROUND: Recent years have seen standardization of the anatomic definitions of
      pancreatic adenocarcinoma, and increasing utilization of neoadjuvant therapy
      (NAT). The aim of the current review was to summarize the evidence for NAT in
      pancreatic adenocarcinoma since 2009, when consensus criteria for resectable (R),
      borderline resectable (BR), and locally advanced (LA) disease were endorsed.
      METHODS: PubMed search was undertaken along with extensive backward search of the
      references of published articles to identify studies utilizing NAT for pancreatic
      adenocarcinoma. Abstracts from ASCO-GI 2014 and 2015 were also searched. RESULTS:
      A total of 96 studies including 5520 patients were included in the final
      quantitative synthesis. Pooled estimates revealed 36% grade >= 3 toxicities, 5%
      biliary complications, 21% hospitalization rate and low mortality (0%, range 0
      16%) during NAT. The majority of patients (59%) had stable disease. On an
      intention-to-treat basis, R0-resection rates varied from 63% among R patients to
      23% among LA patients. R0 rates were > 80% among all patients who were resected
      after NAT. Among R and BR patients who underwent resection after NAT, median OS
      was 30 and 27.4 months, respectively. CONCLUSIONS: The current study summarizes
      the recent literature for NAT in pancreatic adenocarcinoma and demonstrates
      improving outcomes after NAT compared to those historically associated with a
      surgery-first approach for pancreatic adenocarcinoma.

PMID- 29017584
TI  - American trypanosomiasis, or Chagas disease, in Panama: a chronological synopsis
      of ecological and epidemiological research.
AB  - American trypanosomiasis, or Chagas disease, is a growing public health problem
      in Panama, and further forest degradation due to human population growth is
      expected to worsen the situation. Most people infected with the parasite
      Trypanosoma cruzi are silently ill, and their life expectancy is severely
      compromised, which contributes to further deterioration of living conditions in
      endemic regions. Here, we review the outcomes of nearly 100 years of ecological
      and epidemiological investigation about Chagas disease in Panama, in an attempt
      to highlight progress, identify needs, and re-orient future efforts. Rhodnius
      pallescens and Triatoma dimidiata are both primary vectors of T. cruzi in Panama,
      but R. pallescens seems more efficient in human-altered forest ecosystems due to
      a greater degree of association with Attalea butyracea. In contrast, T. dimidiata
      transmits T. cruzi efficiently under more sylvatic conditions (e.g. settlements
      inside old-growth or secondary forest patches), where its populations reach
      considerable numbers irrespective of the absence of A. butyracea. A trend of
      increasing forest degradation, suburbanization, and development of tourism in
      Panama favoring the establishment of A. butyracea and other palm tree species
      (Acrocomia sp.) suggests that a colonist species like R. pallescens will continue
      to play a more prominent role in the transmission of T. cruzi than a forest
      specialist like T. dimidiata. However, studies about the taxonomic status and
      ecology of these vectors are still needed in Panama to address their transmission
      potential fully. The implementation of an active surveillance system and
      education programs could greatly minimize the risk of Chagas disease transmission
      in Panama, preventing fatal infections in children from endemic areas.

PMID- 29017585
TI  - PANSAID-PAracetamol and NSAID in combination: detailed statistical analysis plan
      for a randomised, blinded, parallel, four-group multicentre clinical trial.
AB  - BACKGROUND: Effective postoperative pain management is essential for the
      rehabilitation of the surgical patient. The PANSAID trial evaluates the analgesic
      effects and safety of the combination of paracetamol and ibuprofen. This paper
      describes in detail the statistical analysis plan for the primary publication to
      prevent outcome reporting bias and data-driven analysis results. METHODS/DESIGN:
      The PANSAID trial is a multicentre, randomised, controlled, parallel, four-group
      clinical trial comparing the beneficial and harmful effects of different doses
      and combinations of paracetamol and ibuprofen in patients having total hip
      arthroplastic surgery. Patients, caregivers, physicians, investigators, and
      statisticians are blinded to the intervention. The two co-primary outcomes are 24
      h consumption of morphine and proportion of patients with one or more serious
      adverse events within 90 days after surgery. Secondary outcomes are pain scores
      during mobilisation and at rest at 6 and 24 h postoperatively, and the proportion
      of patients with one or more adverse events within 24 h postoperatively.
      DISCUSSION: PANSAID will provide a large trial with low risk of bias regarding
      benefits and harms of the combination of paracetamol and ibuprofen used in a
      perioperative setting. TRIAL REGISTRATION: ClinicalTrials.org identifier:
      NCT02571361 . Registered on 7 October 2015.

PMID- 29017586
TI  - Impact of prosthesis-patient mismatch after mitral valve replacement in rheumatic
      population: Does mitral position prosthesis-patient mismatch really exist?
AB  - BACKGROUND: Prosthesis-patient mismatch (PPM) is characterised by the effects of
      inadequate prosthesis size relative to body surface area (BSA).The purpose of
      this study was to determine the impact of PPM on late clinical outcomes after
      mitral valve replacement (MVR) in rheumatic population. METHODS: From 2000 to
      2013, a total of 445 patients (mean age 54.2 +/- 11.7 years) underwent isolated
      MVR (+/-tricuspid annuloplasty) for rheumatic disease were investigated.
      Effective orifice area (EOA) was determined by the continuity equation and PPM
      was defined as indexed EOA (EOA/BSA) <= 1.2 cm2/m2. Clinical and
      echocardiographic follow-up (mean follow up 8.7 +/- 4.0 years) results were
      compared. RESULTS: 37% of patients (n = 165) had PPM. There were no significant
      differences in baseline and operative characteristics between patients with and
      without PPM except age and IEOA. A significant decrease in mean trans-valvular
      pressure gradient (MPG) over time following MVR, however the change of MPG showed
      no differences between groups (No PPM vs. PPM: 8.9 +/- 4.7 mmHg -> 3.6 +/- 1.2
      mmHg vs. 8.7 +/- 4.5 mmHg -> 3.8 +/- 1.4 mmHg, p-value = 0.28). In all patients,
      there was a reduction of left atrium dimension (58.6 +/- 12.0 mm -> 53.2 +/- 12.0
      mm vs. 57.9 +/- 8.9 mm -> 52.2 +/- 8.9 mm, p-value = 0.68) and left ventricular
      end diastolic diameter (49.9 +/- 5.7 mm -> 48.9 +/- 5.7 mm vs. 49.7 +/- 6.0 mm ->
      48.3 +/- 5.0 mm, p = 0.24) without statistical significance. Freedom from TR
      progression rates at 3 and 5 years (99% vs.98%, 99% vs. 98%, p-value = 0.1), and
      overall survival rates at 3 and 5 years (97% vs. 96%, 94% vs. 94%, p-value = 0.7)
      were similar. CONCLUSION: This study shows that mitral PPM is not associated with
      atrial /ventricular remodeling and might not influence late clinical outcome
      including late TR progression, survival in rheumatic population.

PMID- 29017587
TI  - The perspective of gender on the Ebola virus using a risk management and
      population health framework: a scoping review.
AB  - BACKGROUND: In the three decades since the first reported case of Ebola virus,
      most known index cases have been consistently traced to the hunting of "bush
      meat", and women have consistently recorded relatively high fatality rates in
      most catastrophic outbreaks. This paper discusses Ebola-related risk factors,
      which constantly interact with cultural values, and provides an insight into the
      link between gender and the risk of contracting infectious diseases, using Ebola
      virus as an example within Africa. METHOD: A comprehensive search of the
      literature was conducted using the PubMed, Ovid Medline and Global Health CABI
      databases as well as CAB Abstracts, including gray literature. We used a
      descriptive and sex- and gender-based analysis to revisit previous studies on
      Ebola outbreaks since 1976 to 2014, and disaggregated the cases and fatality
      rates according to gender and the sources of known index cases based on available
      data. RESULTS: In total, approximately 1530 people died in all previous Ebola
      outbreaks from 1976 to 2012 compared with over 11,310 deaths from the 2014
      outbreak. Women's increased exposure can be attributed to time spent at home and
      their responsibility for caring for the sick, while men's increased vulnerability
      to the virus can be attributed to their responsibility for caring for livestock
      and to time spent away from home, as most known sources of the index cases have
      been infected in the process of hunting. We present a conceptual model of a
      circle of interacting risk factors for Ebola in the African context. CONCLUSION:
      There is currently no evidence related to biological differences in female or
      male sex that increases Ebola virus transmission and vulnerability; rather, there
      are differences in the level of exposure between men and women. Gender is
      therefore an important risk factor to consider in the design of health programs.
      Building the capacity for effective risk communication is a worthwhile investment
      in public and global health for future emergency responses.

PMID- 29017588
TI  - Morbidity and mortality of children aged 2-59 months admitted in the Tanzania
      Lake Zone's public hospitals: a cross-sectional study.
AB  - BACKGROUND: There is a growing concern about child mortality especially in
      developing countries. The Government of Tanzania and non-governmental
      organizations are fighting against diseases like malaria, anaemia, diarrhoea and
      pneumonia that contribute extensively to child mortality. This was a hospital
      based, retrospective cohort study involving 1130 under-fives (excluding neonates)
      being either discharged from or died in public hospitals of the Lake Zone in
      Tanzania. We extracted information on symptoms and signs at admission, major
      diagnoses and causes of death from the medical records. We applied binary
      logistic regression models to assess risk factors associated with in-patient
      under-five death. RESULTS: The major leading morbidities include malaria (49%),
      anemia (37%), diarrhea (27%), pneumonia (22%) and severe acute malnutrition
      (21%). We found the case fatality of 74 deaths per 1000 under-five admissions.
      Major underlying causes of deaths were severe anaemia, severe malaria and severe
      pneumonia. Factors associated with in-patient death were female sex (AOR 1.7; 95%
      CI 1.0, 2.8) and the odds significantly decreased with increasing level of
      maternal education. CONCLUSIONS: Malaria remains a leading cause of admissions in
      hospitals among under-fives. Although the case fatality among children aged
      between 2 and 59 months admitted in hospitals in Lake Zone is decreasing, efforts
      are needed to address major causes of deaths (severe anaemia, severe malaria and
      severe pneumonia).

PMID- 29017589
TI  - Randomized trial of telephone versus in-person delivery of a brief psychosocial
      intervention in post-stroke depression.
AB  - BACKGROUND: A psychosocial behavioral intervention delivered in-person by
      advanced practice nurses has been shown effective in substantially reducing post
      stroke depression (PSD). This follow-up trial compared the effectiveness of a
      shortened intervention delivered by either telephone or in-person to usual care.
      To our knowledge, this is the first of current behavioral therapy trials to
      expand the protocol in a new clinical sample. 100 people with Geriatric
      Depression Scores >= 11 were randomized within 4 months of stroke to usual care
      (N = 28), telephone intervention (N = 37), or in-person intervention (N = 35).
      Primary outcome was response [percent reduction in the Hamilton Depression Rating
      Scale (HDRS)] and remission (HDRS score < 10) at 8 weeks and 12 months post
      treatment. RESULTS: Intervention groups were combined for the primary analysis
      (pre-planned). The mean response in HDRS scores was 39% reduction for the
      combined intervention group (40% in-person; 38% telephone groups) versus 33% for
      the usual care group at 8 weeks (p = 0.3). Remission occurred in 37% in the
      combined intervention groups at 8 weeks versus 27% in the control group (p = 0.3)
      and 44% intervention versus 36% control at 12 months (p = 0.5). While favouring
      the intervention, these differences were not statistically significant.
      CONCLUSIONS: A brief psychosocial intervention for PSD delivered by telephone or
      in-person did not reduce depression significantly more than usual care. However,
      the comparable effectiveness of telephone and in-person follow-up for treatment
      of depression found is important given greater accessibility by telephone and
      mandated post-hospital follow-up for comprehensive stroke centers. Clinical Trial
      Registration URL: https://register.clinicaltrials.gov , unique identifier:
      NCT01133106, Registered 5/26/2010.

PMID- 29017591
TI  - Residual disease activity and treatment adjustments in psoriatic arthritis in
      current clinical practice.
AB  - BACKGROUND: With expanding therapeutic possibilities for treatment of psoriatic
      arthritis (PsA) it will be increasingly important to determine residual disease
      and define when to adjust treatment. The rationale behind treatment decisions in
      current daily clinical practice and the relationship with residual disease
      activity has not been investigated. The aim of this study was to assess current
      clinical practice on defining residual disease and subsequent treatment decisions
      made in PsA patients. METHODS: This cross-sectional study scored disease activity
      and treatment decisions prospectively in 142 consecutive PsA patients visiting
      the outpatient clinic for routine follow up. Disease activity parameters were
      scored by patient and the treating rheumatologist; the rheumatologist
      additionally registered his opinion on the presence of remaining disease activity
      despite current treatment (further mentioned as remaining disease) and subsequent
      treatment decisions. RESULTS: Two thirds (90/142) of patients had remaining
      disease activity according to the treating rheumatologist. Almost half (46%) of
      these patients had moderate to high disease activity according to the clinical
      Disease Activity Index for Psoriatic Arthritis (cDAPSA). Residual disease
      activity was determined by joint disease and pain rather than by active
      psoriasis. Demographic and clinical features were similar between groups with or
      without residual disease. Among patients with remaining disease activity, 74%
      were treated with either a conventional synthetic disease-modifying anti
      rheumatic drug (csDMARD) only or a first TNF-inhibiting biological agent,
      suggesting opportunities for treatment modification. However, treatment
      adjustment was initiated in only 21 (23%) of the 90 patients with residual
      disease. When comparing patients with remaining disease activity with and without
      treatment adjustment, we found no differences in objective disease activity
      measures, such as joint counts and patient scores. These data suggest that
      treatment is not adjusted in a large majority of patients with residual disease
      activity, although options for treatment changes are available. CONCLUSIONS:
      Remaining disease activity is present in almost two thirds of patients with PsA
      when scored by the treating rheumatologist, but triggers treatment adjustment in
      only a minority. Further research to understand why disease activity does not
      lead to treatment adjustment is required to enable implementation of treatment
      strategies in clinical practice.

PMID- 29017590
TI  - Review of the evolution of insecticide resistance in main malaria vectors in
      Cameroon from 1990 to 2017.
AB  - BACKGROUND: Malaria remains a major public health threat in Cameroon and disease
      prevention is facing strong challenges due to the rapid expansion of insecticide
      resistance in vector populations. The present review presents an overview of
      published data on insecticide resistance in the main malaria vectors in Cameroon
      to assist in the elaboration of future and sustainable resistance management
      strategies. METHODS: A systematic search on mosquito susceptibility to
      insecticides and insecticide resistance in malaria vectors in Cameroon was
      conducted using online bibliographic databases including PubMed, Google and
      Google Scholar. From each peer-reviewed paper, information on the year of the
      study, mosquito species, susceptibility levels, location, insecticides, data
      source and resistance mechanisms were extracted and inserted in a Microsoft Excel
      datasheet. The data collected were then analysed for assessing insecticide
      resistance evolution. RESULTS: Thirty-three scientific publications were selected
      for the analysis. The rapid evolution of insecticide resistance across the
      country was reported from 2000 onward. Insecticide resistance was highly
      prevalent in both An. gambiae (s.l.) and An. funestus. DDT, permethrin,
      deltamethrin and bendiocarb appeared as the most affected compounds by
      resistance. From 2000 to 2017 a steady increase in the prevalence of kdr allele
      frequency was noted in almost all sites in An. gambiae (s.l.), with the L1014F
      kdr allele being the most prevalent. Several detoxification genes (particularly
      P450 monooxygenase) were associated with DDT, pyrethroids and bendiocarb
      resistance. In An. funestus, resistance to DDT and pyrethroids was mainly
      attributed to the 119F-GSTe2 metabolic resistance marker and over-expression of
      P450 genes whereas the 296S-RDL mutation was detected in dieldrin-resistant An.
      funestus. CONCLUSIONS: The review provides an update of insecticide resistance
      status in malaria vector populations in Cameroon and stresses the need for
      further actions to reinforce malaria control strategies in the coming years.

PMID- 29017592
TI  - Omentin-1 effects on mesenchymal stem cells: proliferation, apoptosis, and
      angiogenesis in vitro.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) are emerging as an extremely promising
      therapeutic agent for tissue repair. However, limitations exist such as the low
      numbers of MSCs obtained from donors, and the poor survival and function of donor
      cells. Omentin-1, a new fat depot-specific secretory adipokine, exerts
      proproliferation, prosurvival, and proangiogenic functions in certain cells via
      an Akt-dependent mechanism; however, little is known about the influence of
      omentin-1 on MSCs. METHODS: MSCs were isolated from 60-80 g donor rats. Cell
      proliferation was assessed with CCK-8 and EdU assay. Cell cycle, apoptosis ratio,
      reactive oxygen species concentration, and mitochondrial membrane potential were
      detected by flow cytometry. Hoechst 33342 dye was used to assess morphological
      changes of apoptosis. Expression levels of Akt, FoxO3a, GSK-3beta, and apoptosis-
      and cell cycle-associated proteins were detected by Western blotting. Tube
      formation assay was used to test the angiogenesis role of conditioned medium from
      MSCs in vitro. The cytokine secretion was assessed by ELISA. RESULTS: After
      treatment with omentin-1 (100-800 ng/ml), MSCs displayed a higher proliferative
      capacity with an increasing number of cells in the S and G2 phase of the cell
      cycle. Moreover, omentin-1 preconditioning for 1 h could protect MSCs against
      H2O2-induced apoptosis in a concentration-dependent manner. Furthermore, omentin
      1 pretreatment reduced the excessive reactive oxygen species. Western blots
      revealed that increased Bcl-2 and decreased Bax appeared in MSCs after omentin-1
      incubation, which inhibited the mitochondrial apoptosis pathways with evidence
      showing inhibition of caspase-3 cleavage and preservation of mitochondrial
      membrane potential. Omentin-1 could enhance angiogenic growth factor secretion
      and elevate the ability of MSCs to stimulate tube formation by human umbilical
      vein endothelial cells (HUVECs). Furthermore, omentin-1 enhanced Akt
      phosphorylation; however, blockade of the PI3K/Akt pathway with an inhibitor,
      LY294002 (20 MUM), suppressed the above beneficial effects of omentin-1.
      CONCLUSION: Omentin-1 can exert beneficial effects on MSCs by promoting
      proliferation, inhibiting apoptosis, increasing secretion of angiogenic
      cytokines, and enhancing the ability for stimulating tube formation by HUVECs via
      the PI3K/Akt signaling pathway. Thus, omentin-1 may be considered a candidate for
      optimizing MSC-based cell therapy.

PMID- 29017596
TI  - Providers and patients face-to-face: what is the time?
AB  - BACKGROUND: The frequency of visiting primary care providers and the duration of
      those visits varies substantially by patient demographics and across different
      developed countries. The significance of a cumulative measure of this time spent
      with providers in face-to-face visits is not well understood. COMMENTARY: In a
      recent IJHPR issue Nathan and co-authors have suggested a new metric for
      capturing the cumulative time spent annually in face-to-face encounters between
      providers and patients. The annual accumulated duration of time (AADC) of visits
      was constructed using a 2% random sample of adult patients from the Clalit health
      plan in Israel for the year 2012. The authors calculated the mean AADC to be 65.7
      min with average visit durations of 7.6 min. A presumption underlying this
      analysis is that the metric captures the magnitude of activity devoted to
      eliciting relevant clinical information, synthesizing the significance of those
      data, and communicating the importance of that thinking to patients so that they
      might make informed decisions regarding their health care. But measuring the time
      spent with a provider is but a surrogate marker of these activities and the lack
      of correlation between time spent with providers and health outcomes suggests
      that as a surrogate it may not be that robust a measure. It is possible that what
      is being captured through this metric is the influence of economic incentives
      faced by individual practitioners and the structure of health care financing in
      different societies rather than a portrait either of clinical complexity or
      quality of care. CONCLUSIONS: The advent of this new measure of cumulative
      provider time with patients signals the importance of accurate measurement as a
      vital first step in understanding the meaning of data but reminds us of an
      obligation to inquire beyond the measurements themselves to arrive at appropriate
      policy-relevant conclusions.

PMID- 29017594
TI  - Depression in medical students: insights from a longitudinal study.
AB  - BACKGROUND: Factors associated with depression of medical students are poorly
      understood. The purpose of this study is to determine the prevalence of
      depression in medical students, its change during the course, if depression
      persists for affected students, what are the factors associated with depression
      and how these factors change over time. METHODS: A prospective, longitudinal
      observational study was conducted at the Medical School of the University of
      Minho, Portugal, between academic years 2009-2010 to 2012-2013. We included
      students who maintained their participation by annually completing a
      questionnaire including Beck Depression Inventory (BDI). Anxiety and burnout were
      assessed using the State Trait Anxiety Inventory and Maslach Burnout Inventory.
      Surveys on socio-demographic variables were applied to evaluate potential
      predictors, personal and academic characteristics and perceived difficulties.
      ANOVA with multiple comparisons were used to compare means of BDI score. The
      medical students were organized into subgroups by K-means cluster analyses. ANOVA
      mixed-design repeated measurement was performed to assess a possible interaction
      between variables associated with depression. RESULTS: The response rate was 84,
      92, 88 and 81% for academic years 2009-2010, 2010-2011,2011-2012 and 2012/2013,
      respectively. Two hundred thirty-eight medical students were evaluated
      longitudinally. For depression the prevalence ranged from 21.5 to 12.7% (academic
      years 2009/2010 and 2012/2013). BDI scores decreased during medical school. 19.7%
      of students recorded sustained high BDI over time. These students had high levels
      of trait-anxiety and choose medicine for anticipated income and prestige,
      reported more relationship issues, cynicism, and decreased satisfaction with
      social activities. Students with high BDI scores at initial evaluation with low
      levels of trait-anxiety and a primary interest in medicine as a career tended to
      improve their mood and reported reduced burnout, low perceived learning problems
      and increased satisfaction with social activities at last evaluation. No
      difference was detected between men and women in the median BDI score over time.
      CONCLUSIONS: Our findings suggest that personal factors (anxiety traits, medicine
      choice factors, relationship patterns and academic burnout) are relevant for
      persistence of high levels of BDI during medical training. Medical schools need
      to identity students who experience depression and support then, as early as
      possible, particularly when depression has been present over time.

PMID- 29017593
TI  - Incremental value of biomarker combinations to predict progression of mild
      cognitive impairment to Alzheimer's dementia.
AB  - BACKGROUND: The progression of mild cognitive impairment (MCI) to Alzheimer's
      disease (AD) dementia can be predicted by cognitive, neuroimaging, and
      cerebrospinal fluid (CSF) markers. Since most biomarkers reveal complementary
      information, a combination of biomarkers may increase the predictive power. We
      investigated which combination of the Mini-Mental State Examination (MMSE),
      Clinical Dementia Rating (CDR)-sum-of-boxes, the word list delayed free recall
      from the Consortium to Establish a Registry of Dementia (CERAD) test battery,
      hippocampal volume (HCV), amyloid-beta1-42 (Abeta42), amyloid-beta1-40 (Abeta40)
      levels, the ratio of Abeta42/Abeta40, phosphorylated tau, and total tau (t-Tau)
      levels in the CSF best predicted a short-term conversion from MCI to AD dementia.
      METHODS: We used 115 complete datasets from MCI patients of the "Dementia
      Competence Network", a German multicenter cohort study with annual follow-up up
      to 3 years. MCI was broadly defined to include amnestic and nonamnestic
      syndromes. Variables known to predict progression in MCI patients were selected a
      priori. Nine individual predictors were compared by receiver operating
      characteristic (ROC) curve analysis. ROC curves of the five best two-, three-,
      and four-parameter combinations were analyzed for significant superiority by a
      bootstrapping wrapper around a support vector machine with linear kernel. The
      incremental value of combinations was tested for statistical significance by
      comparing the specificities of the different classifiers at a given sensitivity
      of 85%. RESULTS: Out of 115 subjects, 28 (24.3%) with MCI progressed to AD
      dementia within a mean follow-up period of 25.5 months. At baseline, MCI-AD
      patients were no different from stable MCI in age and gender distribution, but
      had lower educational attainment. All single biomarkers were significantly
      different between the two groups at baseline. ROC curves of the individual
      predictors gave areas under the curve (AUC) between 0.66 and 0.77, and all single
      predictors were statistically superior to Abeta40. The AUC of the two-parameter
      combinations ranged from 0.77 to 0.81. The three-parameter combinations ranged
      from AUC 0.80-0.83, and the four-parameter combination from AUC 0.81-0.82. None
      of the predictor combinations was significantly superior to the two best single
      predictors (HCV and t-Tau). When maximizing the AUC differences by fixing
      sensitivity at 85%, the two- to four-parameter combinations were superior to HCV
      alone. CONCLUSION: A combination of two biomarkers of neurodegeneration (e.g.,
      HCV and t-Tau) is not superior over the single parameters in identifying patients
      with MCI who are most likely to progress to AD dementia, although there is a
      gradual increase in the statistical measures across increasing biomarker
      combinations. This may have implications for clinical diagnosis and for selecting
      subjects for participation in clinical trials.

PMID- 29017595
TI  - A series of N-of-1 trials to assess the therapeutic interchangeability of two
      enalapril formulations in the treatment of hypertension in Addis Ababa, Ethiopia:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Hypertension is one of the leading causes of morbidity and mortality
      in Ethiopia. Treatment usually involves lifelong medication use. Enalapril is a
      common drug for the treatment of hypertension in Ethiopia. However, the drug is
      expensive and, therefore, there is limited capacity for people to afford the
      treatment. Locally produced Enalapril is a cost-effective solution to treat the
      disease. However, as local medicines regulation does not include bioequivalence
      tests on locally produced drugs, physicians and patients need assurance about the
      effectiveness and safety of local generics. Evidence on therapeutic equivalence
      is needed on these untested local drugs. METHODS: This is a hospital-based,
      randomized, partially blinded, three-cycle crossover trial in single patients,
      comparing a locally produced version of enalapril with enalapril imported from
      Europe. Patients involved in this trial are not blinded, as there is no local
      facility to produce relatively small numbers of placebos or encapsulated drugs.
      To ensure blinding of study investigators and data analysts, study medications
      are prepared by an independent pharmacy unit using opaque medication packaging.
      The importance of maintaining blinding is also part of patient pre-trial
      education. Each N-of-1 trial will consist of three successive 14-day treatment
      pairs, each pair comprising 7 days of 5-20 mg local and 7 days of 5-20 mg
      imported enalapril taken once daily in the morning. The primary outcome will be
      the average difference in systolic blood pressure as measured by home blood
      pressure measurements. DISCUSSION: The number of locally produced products, such
      as enalapril, being approved without proof of bioequivalence is dramatically
      increasing. By bridging the information gap on bioequivalence, the trial will
      give rigorous evidence on therapeutic equivalence of locally produced enalapril
      in the treatment of hypertension. If there is no difference, the hypothesized
      result, then patients can take the local medicine with confidence. This trial
      will also will determine whether aggregated N-of-1 studies are feasible to
      evaluate untested generic drugs in resource-limited countries where
      bioequivalence testing centers are unavailable. TRIAL REGISTRATION NUMBER:
      Australian and New Zealand Clinical Trial Registry, ID: ACTRN12616001088437p .
      Registered on 12 August 2016.

PMID- 29017597
TI  - Estimating the economic and social consequences for patients diagnosed with human
      African trypanosomiasis in Muchinga, Lusaka and Eastern Provinces of Zambia (2004
      2014).
AB  - BACKGROUND: Acute human African trypanosomiasis (rHAT) caused by Trypanosoma
      brucei rhodesiense is associated with high mortality and is fatal if left
      untreated. Only a few studies have examined the psychological, social and
      economic impacts of rHAT. In this study, mixed qualitative and quantitative
      research methods were used to evaluate the socio-economic impacts of rHAT in
      Mambwe, Rufunsa, Mpika and Chama Districts of Zambia. METHODS: Individuals
      diagnosed with rHAT from 2004 to 2014 were traced using hospital records and
      discussions with communities. Either they, or their families, were interviewed
      using a structured questionnaire and focus group discussions were conducted with
      affected communities. The burden of the disease was investigated using disability
      adjusted life years (DALYs), with and without discounting and age-weighting. The
      impact of long-term disabilities on the rHAT burden was also investigated.
      RESULTS: Sixty four cases were identified in the study. The majority were
      identified in second stage, and the mortality rate was high (12.5%). The total
      number of DALYs was 285 without discounting or age-weighting. When long-term
      disabilities were included this estimate increased by 50% to 462. The proportion
      of years lived with disability (YLD) increased from 6.4% to 37% of the
      undiscounted and un-age-weighted DALY total. When a more active surveillance
      method was applied in 2013-2014 the cases identified increased dramatically,
      suggesting a high level of under-reporting. Similarly, the proportion of females
      increased substantially, indicating that passive surveillance may be especially
      failing this group. An average of 4.9 months of productive time was lost per
      patient as a consequence of infection. The health consequences included pain,
      amnesia and physical disability. The social consequences included stigma,
      dropping out of education, loss of friends and self-esteem. Results obtained from
      focus group discussions revealed misconceptions among community members which
      could be attributed to lack of knowledge about rHAT. CONCLUSIONS: The social and
      economic impact of rHAT on rural households and communities is substantial.
      Improved surveillance and strengthening of local medical services are needed for
      early and accurate diagnosis. Disease prevention should be prioritised in
      communities at risk of rHAT, and interventions put in place to prevent zoonotic
      disease spill over from domestic animals and wildlife. Supportive measures to
      mitigate the long-term effects of disability due to rHAT are needed.

PMID- 29017598
TI  - Behcet's disease risk association fine-mapped on the IL23R-IL12RB2 intergenic
      region in Koreans.
AB  - BACKGROUND: Behcet's disease (BD) susceptibility had been associated with single
      nucleotide polymorphisms (SNPs) in IL23R-IL12RB2, IL10, STAT4, or ERAP1 locus in
      Japanese, Turkish, Chinese, and other populations, but not in a Korean genome
      wide association study (GWAS). We aimed to fine-map BD risk association of these
      four loci using extensive imputation and additional genotyping for replication.
      METHODS: In the discovery phase, 369 patients with BD enrolled in the previous
      Korean GWAS and 2000 controls retrieved from a population-based cohort of healthy
      Koreans were imputed for their genotypes of all SNPs in the four loci using the
      Asian data of the 1000 Genomes Project as reference. For genotype imputation of
      ERAP1 SNPs, the adjacent ERAP2 SNPs were also covered. For the 10 most
      significantly associated SNPs (8 imputed and 2 GWAS-genotyped), an additional 84
      patients with BD and 283 healthy controls were genotyped for replication. The
      results from the discovery and replication phases were pooled for meta-analysis
      using the Mantel-Haenszel test to estimate the odds ratio (OR) and 95% confidence
      interval (CI). RESULTS: An IL23R-IL12RB2 intergenic SNP rs1495965 was
      significantly associated with BD risk (OR (95% CI) = 1.5 (1.3, 1.7), P = 2.5 * 10
      7) in the pooled meta-analysis of the discovery (1.4 (1.2, 1.7), P = 4.9 * 10-7)
      and replication (1.9 (1.3, 2.6), P = 6.0 * 10-4) phases. BD risk association was
      fine-mapped on the intergenic region rather than the two flanking genes, as
      rs1495966 and rs4655535, almost perfectly correlated with rs1495965 (r 2 = 0.99),
      were also located in the same intergenic region. Consistent with previous
      reports, the P values tended to be lower within IL23R than IL12RB2. On the other
      hand, several IL10 SNPs were suggested for association in the discovery phase but
      all failed in the replication phase. No SNP in ERAP1-ERAP2 and STAT4 was
      suggested even in the discovery phase. CONCLUSIONS: BD susceptibility association
      was fine-mapped on the intergenic region between IL23R and IL12RB2 as marked by
      three correlated SNPs, rs1495965, rs1495966, and rs4655535.

PMID- 29017599
TI  - Detection and phylogenetic analyses of spike genes in porcine epidemic diarrhea
      virus strains circulating in China in 2016-2017.
AB  - BACKGROUND: Large-scale outbreaks of porcine epidemic diarrhea (PED) have re
      emerged in China in recent years. However, little is known about the genetic
      diversity and molecular epidemiology of field strains of PED virus (PEDV) in
      China in 2016-2017. To address this issue, in this study, 116 diarrhea samples
      were collected from pig farms in 6 Chinese provinces in 2016-2017 and were
      detected using PCR for main porcine enteric pathogens, including PEDV, porcine
      deltacoronavirus (PDCoV), porcine transmissible gastroenteritis virus (TGEV) and
      porcine kobuvirus (PKV). In addition, the complete S genes from 11 representative
      PEDV strains were sequenced and analyzed. RESULTS: PCR detection showed that
      52.6% (61/116) of these samples were positive for PEDV. Furthermore, sequencing
      results for the spike (S) genes from 11 of the epidemic PEDV strains showed 93
      94% nucleotide identity and 92-93% amino acid identity with the classical CV777
      strain. Compared with the CV777 vaccine strain, these strains had an insertion
      (A133), a deletion (G155), and a continuous 4-amino-acid insertion (56NNTN59) in
      the S1 region. Phylogenetic analysis based on the S gene indicated that the 11
      assessed PEDV strains were genetically diverse and clustered into the G2 group.
      These results demonstrate that the epidemic strains of PEDV in China in 2016-2017
      are mainly virulent strains that belong to the G2 group and genetically differ
      from the vaccine strain. Importantly, this is the first report that the samples
      collected in Hainan Province were positive for PEDV (59.2%, 25/42). CONCLUSIONS:
      To our knowledge, this article presents the first report of a virulent PEDV
      strain isolated from Hainan Island, China. The results of this study will
      contribute to the understanding of the epidemiology and genetic characteristics
      of PEDV in China.

PMID- 29017600
TI  - Ions doped melanin nanoparticle as a multiple imaging agent.
AB  - BACKGROUND: Multimodal nanomaterials are useful for providing enhanced diagnostic
      information simultaneously for a variety of in vivo imaging methods. According to
      our research findings, these multimodal nanomaterials offer promising
      applications for cancer therapy. RESULTS: Melanin nanoparticles can be used as a
      platform imaging material and they can be simply produced by complexation with
      various imaging active ions. They are capable of specifically targeting epidermal
      growth factor receptor (EGFR)-expressing cancer cells by being anchored with a
      specific antibody. Ion-doped melanin nanoparticles were found to have high
      bioavailability with long-term stability in solution, without any cytotoxicity in
      both in vitro and in vivo systems. CONCLUSION: By combining different imaging
      modalities with melanin particles, we can use the complexes to obtain faster
      diagnoses by computed tomography deep-body imaging and greater detailed
      pathological diagnostic information by magnetic resonance imaging. The ion-doped
      melanin nanoparticles also have applications for radio-diagnostic treatment and
      radio imaging-guided surgery, warranting further proof of concept experimental.

PMID- 29017601
TI  - Mass-like Dieulafoy's lesion associated with advanced gastric cancer at the
      antrum of stomach: a case report and literature review.
AB  - BACKGROUND: Dieulafoy's lesion, also known as a caliber-persistent artery, is a
      shallow, small, and rare lesion that occurs along the lesser curvature of
      proximal stomach. It is rare for a Dieulafoy's lesion to present as a mass-like
      lesion that coexists with gastric cancer. To our best knowledge, we report the
      first case and histopathological pictures of a mass-like Dieulafoy's lesion
      coexisting with advanced gastric cancer in the antrum of the stomach. CASE
      PRESENTATION: A 57-year-old female presented with a 6-month history of
      intermittent epigastric dull pain and dyspepsia. Subsequent upper
      gastrointestinal endoscopy revealed a friable mass that was located between the
      distal antrum and the pyloric ring. Biopsy revealed it to be an intestinal type
      adenocarcinoma. Subtotal gastrectomy was performed after neoadjuvant
      chemotherapy. Grossly, a large irregular plaque-like tumor lesion was noted at
      the anterior wall of the distal antrum and pylorus ring near the lesser
      curvature, measuring 5.6 * 4.8 * 1.0 cm. Histopathological examination of the
      resected stomach revealed that the plaque-like lesion largely consisted of
      numerous abnormally large-caliber and tortuous arteries in the submucosa. The
      increased fibrosis of the submucosa resulted in the formation of elevated plaque.
      The intestinal type adenocarcinoma was noted to be largely confined to the mucosa
      layer, with focal submucosal and muscular propria involvement. The patient was
      discharged one week after the subtotal gastrectomy, and she was alive and well 17
      months after discharge, with no major complications. CONCLUSION: This is the
      first case of a mass-like Dieulafoy's lesion coexisting with advanced gastric
      cancer at the distal antrum area. This case highlights the possibility of life
      threatening gastric bleeding after mucosal resection or biopsy that could be
      encountered by endoscopists.

PMID- 29017602
TI  - Phylogenetic analyses reveal that Schellackia parasites (Apicomplexa) detected in
      American lizards are closely related to the genus Lankesterella: is the range of
      Schellackia restricted to the Old World?
AB  - BACKGROUND: Species of Schellackia Reichenow, 1919 have been described from the
      blood of reptiles distributed worldwide. Recently, Schellackia spp. detected in
      European and Asian lizards have been molecularly characterised. However,
      parasites detected in American lizard hosts remain uncharacterised. Thus,
      phylogenetic affinities between the Old and New World parasite species are
      unknown. METHODS: In the present study, we characterised morphologically and
      molecularly the hemococcidian parasites (sporozoites) that infect three lizard
      hosts from North America and two from South America. RESULTS: In total, we
      generated 12 new 18S rRNA gene sequences of hemococcidian parasites infecting New
      World lizard hosts. By the microscopic examination of the smears we identified
      Schellackia golvani Rogier & Landau, 1975 (ex Anolis carolinensis Voigt) and
      Schellackia occidentalis Bonorris & Ball, 1955 (ex Uta stansburiana Baird &
      Girard and Sceloporus occidentalis Baird & Girard) in some samples, but the
      phylogenetic analysis indicated that all 18S rDNA sequences are distant from
      Schellackia species found in Old World lizards. In fact, the hemococcidian
      parasites detected in the New World lizards (including S. occidentalis and S.
      golvani) were closely related to the genus Lankesterella Labbe, 1899.
      Consequently, we suggest these two species to be included within the genus
      Lankesterella. CONCLUSIONS: Life history traits of hemococcidian parasites such
      as the type of host blood cells infected, host species or number of refractile
      bodies are not valid diagnostic characteristics to differentiate the parasites
      between the genera Schellackia and Lankesterella. Indeed, lankesterellid
      parasites with a different number of refractile bodies had a close phylogenetic
      origin. Based on the phylogenetic results we provide a systematic revision of the
      North American hemococcidians. Our recommendation is to include the species
      formerly described in the genus Schellackia that infect American lizards into
      Lankesterella (Lankesterellidae) as Lankesterella golvani (Rogier & Landau, 1975)
      n. comb and L. occidentalis (Bonorris & Ball, 1955) n. comb.

PMID- 29017603
TI  - Longitudinal study of influenza A virus circulation in a nursery swine barn.
AB  - Commercial production of swine often involves raising animals in large groups
      through the use of multi-stage production systems. In such systems, pigs can
      experience different degrees of contact with animals of the same or different
      ages. Population size and degree of contact can greatly influence transmission of
      endemic pathogens, including influenza A virus (IAV). IAV can display high
      genetic variability, which can further complicate population-level patterns. Yet,
      the IAV transmission in large multi-site swine production systems has not been
      well studied. The objectives of this study were to describe the IAV circulation
      in a multi-source nursery facility and identify factors associated with infection
      in nursery pigs. Pigs from five sow herds were mixed in one all-in/all-out
      nursery barn, with 81 and 75 pigs included in two longitudinal studies. Virus
      isolation was performed in Madin-Darby canine kidney cells and serology was
      performed using hemagglutination inhibition assays. Risk factor analysis for
      virological positivity was conducted using logistic regression and stratified
      Cox's regression for recurrent events. In Study 1, at ~30 days post-weaning, 100%
      of pigs were positive, with 43.2% of pigs being positive recurrently over the
      entire study period. In study 2, 48% of pigs were positive at the peak of the
      outbreak, and 10.7% were positive recurrently over the entire study period. The
      results suggest that IAV can circulate during the nursery phase in an endemic
      pattern and that the likelihood of recurrent infections was associated in a non
      linear way with the level of heterologous (within-subtype) maternal immunity (p <
      0.05). High within-pen intracluster correlation coefficients (> 0.75) were also
      observed for the majority of sampling times suggesting that pen-level factors
      played a role in infection dynamics in this study.

PMID- 29017604
TI  - IL-17-differentiated macrophages secrete pro-inflammatory cytokines in response
      to oxidized low-density lipoprotein.
AB  - BACKGROUND: Cytokines and macrophages play a central role in the development of
      atherosclerosis. Interleukin (IL)-17 is a pro-inflammatory cytokine with
      differential effects on innate immune cells. We investigated the effects of IL-17
      on macrophage differentiation and foam cell formation and activation in response
      to oxidized low-density lipoprotein (oxLDL). METHODS: Human monocytes were
      treated with IL-17 to induce macrophage differentiation. As controls, human
      monocytes were differentiated into M1 macrophages (M1) or M2 macrophages (M2).
      Subsequently, we analyzed the expression levels of markers such as CD80, CD36 and
      Toll-like receptors (TLRs) as well as foam cell formation and cytokines in M1, M2
      and macrophages differentiated with IL-17 with or without oxLDL. RESULTS: The
      expression of M1 or M2 markers or cytokines was not induced in macrophages
      differentiated with IL-17. Macrophages differentiated with IL-17 formed few foam
      cells, with an average proportion of 20%, and expressed 3 times as much TLR2 and
      3.8 times as much TLR4 as M0 macrophages. Additionally, macrophages
      differentiated with IL-17 acquired inflammatory capacity in response to oxLDL
      through the expression of specific markers, such as CD80, which increased 18
      times compared with macrophages differentiated with IL-17 alone, and secreted 1.3
      times less tumor necrosis factor (TNF)-alpha than M1. Additionally, oxLDL
      increased the levels of CD80, CD86 and IL-6 by 5.7, 2.8 and 1.4 times in M1
      compared with M1 in the absence of oxLDL. In M2, oxLDL induced increases in the
      secretion of IL-6 and TNF-alpha that were 1.9 times and 1.2 times smaller,
      respectively, than those observed in M1. CONCLUSION: Our study demonstrates that
      differentiation of macrophages with IL-17 does not induce the expression of
      markers or cytokines characteristic of M1 or M2 and these macrophages form few
      foam cells; however, the expression of TLR is increased. Moreover, these
      macrophages acquire the inflammatory capacity as evidenced by the expression of
      costimulatory molecules and secretion of pro-inflammatory cytokines in response
      to oxLDL. These findings suggest that the activation of macrophages
      differentiated with IL-17 by oxLDL contributes to the inflammatory process of
      atherosclerosis.

PMID- 29017605
TI  - COllaborative Shared care to IMprove Psychosis Outcome (COSIMPO): study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: Psychotic disorders are a group of severe mental disorders that cause
      considerable disability to sufferers and a high level of burden to families. In
      many low- and middle-income countries (LMIC), traditional and faith healers are
      the main providers of care to affected persons. Even though frequently canvassed
      as desirable for improved care delivery, collaboration between these
      complementary alternative health providers (CAPs) and conventional health
      providers has yet to be rigorously tested for feasibility and effectiveness on
      patient outcomes. METHODS/DESIGN: COSIMPO is a single-blind, cluster randomized
      controlled trial (RCT) being conducted in Nigeria and Ghana to compare the
      effectiveness of a collaborative shared care (CSC) intervention program
      implemented by CAPs and primary health care providers (PHCPs) with care as usual
      (CAU) at improving the outcome of patients with psychosis. The study is designed
      to test the hypotheses that patients receiving CSC will have a better clinical
      outcome and experience fewer harmful treatment practices from the CAPs than
      patients receiving CAU at 6 months after study entry. An estimated sample of 296
      participants will be recruited from across 51 clusters, with a cluster consisting
      of a primary care clinic and its neighboring CAP facilities. CSC is a manualized
      intervention package consisting of regular and scheduled visits of PHCPs to CAP
      facilities to assist with the management of trial participants. Assistance
      includes the administration of antipsychotic medications, management of comorbid
      physical condition, assisting the CAP to avoid harmful treatment practices, and
      engaging with CAPs, caregivers and participants in planning discharge and
      rehabilitation. The primary outcome, assessed at 6 months following trial entry,
      is improvement on the Positive and Negative Symptom Scale (PANSS). Secondary
      outcomes, assessed at 3 and 6 months, consist of levels of disability, experience
      of harmful treatment practices and of victimization, and levels of perceived
      stigma and of caregivers' burden. DISCUSSION: Information about whether
      collaboration between orthodox and complementary health providers is feasible and
      can lead to improved outcome for patients is important to formulating policies
      designed to formally engage the services of traditional and faith healers within
      the public health system. TRIAL REGISTRATION: National Institutes of Health
      Clinical Trial registry, ID: NCT02895269 . Registered on 30 July 2016.

PMID- 29017606
TI  - Temporal distribution and insecticide resistance profile of two major arbovirus
      vectors Aedes aegypti and Aedes albopictus in Yaounde, the capital city of
      Cameroon.
AB  - BACKGROUND: Aedes aegypti and Ae. albopictus are the major epidemic vectors of
      several arbovirus diseases such as yellow fever, dengue, Zika and chikungunya
      worldwide. Both Aedes vectors are presents in Cameroon; however, knowledge on the
      dynamic of the distribution of these species across cities and their resistance
      profile to insecticide are limited. Here, we assessed the current distribution of
      Ae. aegypti and Ae. albopictus in Yaounde, the Capital City, established the
      resistance profile to insecticides and explored the resistance mechanisms
      involved. METHODS: Immature stages of Aedes were sampled in several breeding
      sites in December 2015 (dry season) and June 2016 (rainy season) in three central
      neighborhoods and four peripheral neighborhoods and reared to adult stage. The G0
      adults were used for molecular identification and genotyping of F1534C mutation
      in Ae. aegypti. Bioassays and piperonyl butoxide (PBO) assays were carried out
      according to WHO guidelines. RESULTS: Analysis revealed that both species Ae.
      aegypti and Ae. albopictus are present in all prospected sites in Yaounde.
      However, in the dry season Ae. aegypti is most abundant in neighborhoods located
      in downtown. In contrast, Ae. albopictus was found most prevalent in suburbs
      whatever the season and in downtown during the rainy season. Bioassay analysis
      showed that both Ae. aegypti and Ae. albopictus, are resistant to 0.05%
      deltamethrin, 0.1% bendiocarb and 4% dichlorodiphenyltrichloroethane (DDT). A
      decreased of susceptibility to 0.75% permethrin and a full susceptibility to
      malathion 5% was observed. The mortality rate was increased after pre-exposure to
      synergist PBO. None of Ae. aegypti assayed revealed the presence of F1534C
      mutation. CONCLUSION: These findings are useful to planning vector control
      programme against arbovirus vectors in Cameroon and can be used as baseline in
      Africa where data on Aedes resistance is very scarce to plan further works.

PMID- 29017607
TI  - Non-digestible oligosaccharides directly regulate host kinome to modulate host
      inflammatory responses without alterations in the gut microbiota.
AB  - BACKGROUND: Prebiotics are non-digestible food ingredients that enhance the
      growth of certain microbes within the gut microbiota. Prebiotic consumption
      generates immune-modulatory effects that are traditionally thought to reflect
      microbial interactions within the gut. However, recent evidence suggests they may
      also impart direct microbe-independent effects on the host, though the mechanisms
      of which are currently unclear. METHODS: Kinome arrays were used to profile the
      host intestinal signaling responses to prebiotic exposures in the absence of
      microbes. Identified pathways were functionally validated in Caco-2Bbe1
      intestinal cell line and in vivo model of murine endotoxemia. RESULTS: We found
      that prebiotics directly regulate host mucosal signaling to alter response to
      bacterial infection. Intestinal epithelial cells (IECs) exposed to prebiotics are
      hyporesponsive to pathogen-induced mitogen-activated protein kinase (MAPK) and
      nuclear factor kappa B (NF-kappaB) activations, and have a kinome profile
      distinct from non-treated cells pertaining to multiple innate immune signaling
      pathways. Consistent with this finding, mice orally gavaged with prebiotics
      showed dampened inflammatory response to lipopolysaccharide (LPS) without
      alterations in the gut microbiota. CONCLUSIONS: These findings provide molecular
      mechanisms of direct host-prebiotic interactions to support prebiotics as potent
      modulators of host inflammation.

PMID- 29017608
TI  - Autologous mesenchymal stem cells or meniscal cells: what is the best cell source
      for regenerative meniscus treatment in an early osteoarthritis situation?
AB  - BACKGROUND: Treatment of meniscus tears within the avascular region represents a
      significant challenge, particularly in a situation of early osteoarthritis. Cell
      based tissue engineering approaches have shown promising results. However,
      studies have not found a consensus on the appropriate autologous cell source in a
      clinical situation, specifically in a challenging degenerative environment. The
      present study sought to evaluate the appropriate cell source for autologous
      meniscal repair in a demanding setting of early osteoarthritis. METHODS: A rabbit
      model was used to test autologous meniscal repair. Bone marrow and medial menisci
      were harvested 4 weeks prior to surgery. Bone marrow-derived mesenchymal stem
      cells (MSCs) and meniscal cells were isolated, expanded, and seeded onto collagen
      hyaluronan scaffolds before implantation. A punch defect model was performed on
      the lateral meniscus and then a cell-seeded scaffold was press-fit into the
      defect. Following 6 or 12 weeks, gross joint morphology and OARSI grade were
      assessed, and menisci were harvested for macroscopic, histological, and
      immunohistochemical evaluation using a validated meniscus scoring system. In
      conjunction, human meniscal cells isolated from non-repairable bucket handle
      tears and human MSCs were expanded and, using the pellet culture model, assessed
      for their meniscus-like potential in a translational setting through collagen
      type I and II immunostaining, collagen type II enzyme-linked immunosorbent assay
      (ELISA), and gene expression analysis. RESULTS: After resections of the medial
      menisci, all knees showed early osteoarthritic changes (average OARSI grade 3.1).
      However, successful repair of meniscus punch defects was performed using either
      meniscal cells or MSCs. Gross joint assessment demonstrated donor site morbidity
      for meniscal cell treatment. Furthermore, human MSCs had significantly increased
      collagen type II gene expression and production compared to meniscal cells (p <
      0.05). CONCLUSIONS: The regenerative potential of the meniscus by an autologous
      cell-based tissue engineering approach was shown even in a challenging setting of
      early osteoarthritis. Autologous MSCs and meniscal cells were found to have
      improved meniscal healing in an animal model, thus demonstrating their
      feasibility in a clinical setting. However, donor site morbidity, reduced
      availability, and reduced chondrogenic differentiation of human meniscal cells
      from debris of meniscal tears favors autologous MSCs for clinical use for cell
      based meniscus regeneration.

PMID- 29017610
TI  - HIV among people who inject drugs in Hungary.
AB  - BACKGROUND: Before 2014 (the year of closure of the two largest needle exchange
      programs in Hungary, which halved the number of available syringes in the country
      despite increased injecting risk practices) no HIV was reportedly acquired in
      Hungary among people who inject drugs (PWIDs) who were not also men who had sex
      with other men (MSM). In 2014, one and in 2015 two non-MSM PWIDs were newly
      diagnosed with HIV who supposedly became infected in Hungary, and both incident
      HIV cases in 2015 were diagnosed in the AIDS stage. In addition, two new (albeit
      supposedly imported) non-MSM PWID cases were also registered in the first three
      quarters of 2016, one of which subsequently was diagnosed with and then died of
      AIDS. At the same time, the prevalence of HCV doubled among PWIDs (from 24% to
      49% in Hungary and from 34% to 61% in Budapest). CASE PRESENTATION: The case that
      we discuss in this paper is a male PWID, who was diagnosed with HIV and AIDS in
      May of 2015 and then died of AIDS the next month. His HIV infection status was
      detected with delay, and then appeared in the official statistics as an incident
      PWID HIV case and an incident PWID AIDS case, but not as an incident PWID AIDS
      death. No contact tracing followed, even though it would have been relatively
      easy considering the circumstances. To our knowledge, no HIV post-exposure
      protocol exists in hospitals, in case of HIV exposure due to an eventual needle
      stick injury. CONCLUSIONS: Our paper draws attention to recently published HIV
      and AIDS surveillance data, and shows the failure of the system. While sounding
      the alarm based on three newly detected PWID HIV cases in the past 2 years may be
      premature, there are definitely serious problems in the HIV detection and tracing
      system among PWIDs in Hungary.

PMID- 29017609
TI  - Effects of intra-arterial transplantation of adipose-derived stem cells on the
      expression of netrin-1 and its receptor DCC in the peri-infarct cortex after
      experimental stroke.
AB  - BACKGROUND: Stem cell transplantation has been documented to promote functional
      recovery in animal models of stroke; however, the underlying mechanisms are not
      yet fully understood. As netrin-1 and its receptor deleted in colorectal cancer
      (DCC) are important regulators in neuronal and vascular activities, the present
      study attempted to explore whether netrin-1 and DCC are involved in the
      neuroprotection of stem cell-based therapies in a rat ischemic stroke model.
      METHODS: Adult male Sprague-Dawley rats were subjected to a transient middle
      cerebral artery occlusion (MCAO) and subsequently received an intra-arterial
      injection of 2 * 106 PKH26-labeled adipose-derived stem cells (ADSCs) or saline
      24 h later. Neurological function was evaluated by behavioral tests before the
      rats were sacrificed at days 7 and 14 after MCAO. The migration of ADSCs and
      regeneration of neuronal fibers and blood vessels were determined by
      immunofluorescence staining. The expression of netrin-1 and DCC was analyzed by
      Western blot and immunofluorescence staining. RESULTS: ADSC transplantation
      significantly improved the neurological recovery at days 7 and 14, and noticeably
      promoted the regeneration of neuronal fibers and blood vessels in the peri
      infarct cortex at day 14. PKH26-labeled ADSCs located mainly in the peri-infarct
      area at days 7 and 14. In ADSC-treated rats, the expression of netrin-1 and DCC
      significantly increased in the peri-infarct cortex at days 7 and 14.
      Immunofluorescence staining showed that netrin-1 was mainly expressed by neuronal
      perikaryal in the peri-infarct cortex, and DCC was mainly expressed by neuronal
      fibers and was present around the blood vessels in the peri-infarct cortex.
      CONCLUSIONS: These findings suggest that ADSC transplantation facilitates the
      regeneration of neuronal fibers and blood vessels in the peri-infarct cortex and
      improves neurological functions, which may be attributed, at least in part, to
      the involvement of upregulated netrin-1 and DCC in the remodeling of neuronal and
      vascular networks in the peri-infarct cortex.

PMID- 29017611
TI  - Amplicon sequencing of bacterial microbiota in abortion material from cattle.
AB  - Abortions in cattle have a significant economic impact on animal husbandry and
      require prompt diagnosis for surveillance of epizootic infectious agents. Since
      most abortions are not epizootic but sporadic with often undetected etiologies,
      this study examined the bacterial community present in the placenta (PL, n = 32)
      and fetal abomasal content (AC, n = 49) in 64 cases of bovine abortion by next
      generation sequencing (NGS) of the 16S rRNA gene. The PL and AC from three
      fetuses of dams that died from non-infectious reasons were included as controls.
      All samples were analyzed by bacterial culture, and 17 were examined by
      histopathology. We observed 922 OTUs overall and 267 taxa at the genus level. No
      detectable bacterial DNA was present in the control samples. The microbial
      profiles of the PL and AC differed significantly, both in their composition
      (PERMANOVA), species richness and Chao-1 (Mann-Whitney test). In both organs,
      Pseudomonas was the most abundant genus. The combination of NGS and culture
      identified opportunistic pathogens of interest in placentas with lesions, such as
      Vibrio metschnikovii, Streptococcus uberis, Lactococcus lactis and Escherichia
      coli. In placentas with lesions where culturing was unsuccessful, Pseudomonas and
      unidentified Aeromonadaceae were identified by NGS displaying high number of
      reads. Three cases with multiple possible etiologies and placentas presenting
      lesions were detected by NGS. Amplicon sequencing has the potential to uncover
      unknown etiological agents. These new insights on cattle abortion extend our
      focus to previously understudied opportunistic abortive bacteria.

PMID- 29017612
TI  - A pilot study of hot-wire, ultrasonic and wedge-bellows spirometer inter- and
      intra-variability.
AB  - OBJECTIVE: The aim of this pilot study was to compare spirometric values obtained
      with different types of spirometers, spirometers of same type, and repeated
      measurements with the same spirometer in a pulmonary function laboratory setting.
      RESULTS: 12 healthy volunteers performed spirometry on four hot-wire
      (SensorMedics), two ultrasonic (Spirare) and one wedge-bellows (Vitalograph S)
      spirometers, according to ATS/ERS (American Thoracic Society/European Respiratory
      Society) guidelines. Spirometric values were compared using linear mixed models
      analysis with a random intercept for subjects and a fixed effect for type of
      spirometer used. Confidence intervals and p values were adjusted for multiple
      comparisons. Mean +/- SD (L) values for hot-wire, ultrasonic and wedge-bellows
      spirometers for FVC (forced vital capacity) were 4.02 +/- 0.66, 3.69 +/- 0.61 and
      3.93 +/- 0.69, and for FEV1 (forced expiratory volume in one second) 3.06 +/-
      0.44, 2.95 +/- 0.44 and 3.10 +/- 0.49. Significant differences were found between
      hot-wire and ultrasonic and between wedge-bellows and ultrasonic spirometers for
      FVC and FEV1, and between hot-wire and wedge-bellows spirometers for FVC but not
      for FEV1. There were no significant differences between spirometers of same type,
      and low mean differences in repeated measurements for all spirometers included.
      In conclusion, the pilot study shows systematically higher values for FVC and
      FEV1 for hot-wire and wedge-bellows compared to ultrasonic spirometers.

PMID- 29017614
TI  - Recovery test results as a prerequisite for publication of gaseous exchange
      measurements.

PMID- 29017613
TI  - A multiplex PCR for detection of knockdown resistance mutations, V1016G and
      F1534C, in pyrethroid-resistant Aedes aegypti.
AB  - BACKGROUND: Mutation of the voltage-gated sodium channel (VGSC) gene, or
      knockdown resistance (kdr) gene, is an important resistance mechanism of the
      dengue vector Aedes aegypti mosquitoes against pyrethroids. In many countries in
      Asia, a valine to glycine substitution (V1016G) and a phenylalanine to cysteine
      substitution (F1534C) are common in Ae. aegypti populations. The G1016 and C1534
      allele frequencies have been increasing in recent years, and hence there is a
      need to have a simple and inexpensive tool to monitor the alleles in large scale.
      METHODS: A multiplex PCR to detect V1016G and F1534C mutations has been developed
      in the current study. This study utilized primers from previous studies for
      detecting the mutation at position 1016 and newly designed primers to detect
      variants at position 1534. The PCR conditions were validated and compared with
      DNA sequencing using known kdr mutant laboratory strains and field collected
      mosquitoes. The efficacy of this method was also compared with allele-specific
      PCR (AS-PCR). RESULTS: The results of our multiplex PCR were in complete
      agreement with sequencing data and better than the AS-PCR. In addition, the
      efficiency of two non-toxic DNA staining dyes, UltrapowerTM and RedSafeTM, were
      evaluated by comparing with ethidium bromide (EtBr) and the results were
      satisfactory. CONCLUSIONS: Our multiplex PCR method is highly reliable and useful
      for implementing vector surveillance in locations where the two alleles co-occur.

PMID- 29017615
TI  - Development of equations to predict the influence of floor space on average daily
      gain, average daily feed intake and gain : feed ratio of finishing pigs.
AB  - Floor space allowance for pigs has substantial effects on pig growth and welfare.
      Data from 30 papers examining the influence of floor space allowance on the
      growth of finishing pigs was used in a meta-analysis to develop alternative
      prediction equations for average daily gain (ADG), average daily feed intake
      (ADFI) and gain : feed ratio (G : F). Treatment means were compiled in a database
      that contained 30 papers for ADG and 28 papers for ADFI and G : F. The predictor
      variables evaluated were floor space (m2/pig), k (floor space/final BW0.67),
      Initial BW, Final BW, feed space (pigs per feeder hole), water space (pigs per
      waterer), group size (pigs per pen), gender, floor type and study length (d).
      Multivariable general linear mixed model regression equations were used. Floor
      space treatments within each experiment were the observational and experimental
      unit. The optimum equations to predict ADG, ADFI and G : F were: ADG,
      g=337.57+(16 468*k)-(237 350*k 2)-(3.1209*initial BW (kg))+(2.569*final BW
      (kg))+(71.6918*k*initial BW (kg)); ADFI, g=833.41+(24 785*k)-(388 998*k 2)
      (3.0027*initial BW (kg))+(11.246*final BW (kg))+(187.61*k*initial BW (kg)); G :
      F=predicted ADG/predicted ADFI. Overall, the meta-analysis indicates that BW is
      an important predictor of ADG and ADFI even after computing the constant
      coefficient k, which utilizes final BW in its calculation. This suggests
      including initial and final BW improves the prediction over using k as a
      predictor alone. In addition, the analysis also indicated that G : F of finishing
      pigs is influenced by floor space allowance, whereas individual studies have
      concluded variable results.

PMID- 29017617
TI  - Birth weight and postnatal microbial exposures predict the distribution of
      peripheral blood leukocyte subsets in young adults in the Philippines.
AB  - The immune system not only provides protection against infectious disease but
      also contributes to the etiology of neoplastic, atopic, and cardiovascular and
      metabolic diseases. Prenatal and postnatal nutritional and microbial environments
      have lasting effects on multiple aspects of immunity, indicating that immune
      processes may play important roles in the developmental origins of disease. The
      objective of this study is to evaluate the association between birth weight and
      the distribution of leukocyte (white blood cell) subsets in peripheral blood in
      young adulthood. Postnatal microbial exposures were also considered as predictors
      of leukocyte distribution. Participants (n=486; mean age=20.9 years) were drawn
      from a prospective birth cohort study in the Philippines, and analyses focused on
      the following cell types: CD4 T lymphocytes, CD8 T lymphocytes, B lymphocytes,
      natural killer cells, monocytes, granulocytes. Higher birth weight was a strong
      predictor of higher proportion of CD4 T lymphocytes (B=0.12, s.e.=0.041,
      P=0.003), lower proportion of CD8 T lymphocytes (B=-0.874, s.e.=0.364, P=0.016),
      higher CD4:CD8 ratio (B=1.964, s.e.=0.658, P=0.003), and higher B lymphocytes
      (B=0.062, s.e.=0.031, P=0.047). Measures of microbial exposure in infancy were
      negatively associated with proportions of B lymphocytes and granulocytes, and
      lower CD4:CD8 ratio. Leukocytes are the key regulators and effectors of innate
      and specific immunity, but the origins of variation in the distribution of cell
      type across individuals are not known. Our findings point toward nutritional and
      microbial exposures in infancy as potentially important determinants of immune
      phenotypes in adulthood, and they suggest that leukocyte distribution is a
      plausible mechanism through which developmental environments have lasting effects
      on disease risk in adulthood.

PMID- 29017616
TI  - Quantitative interferon-gamma responses predict future disease progression in
      badgers naturally infected with Mycobacterium bovis.
AB  - The diagnosis and control of Mycobacterium bovis infection (bovine tuberculosis:
      TB) continues to present huge challenges to the British cattle industry. A
      clearer understanding of the magnitude and duration of immune response to M.
      bovis infection in the European badger (Meles meles) - a wildlife maintenance
      host - may assist with the future development of diagnostic tests, and
      vaccination and disease management strategies. Here, we analyse 5280 diagnostic
      test results from 550 live wild badgers from a naturally-infected population to
      investigate whether one diagnostic test (a gamma interferon release [IFNgamma]
      assay, n = 550 tests) could be used to predict future positive results on two
      other tests for the same disease (a serological test [n = 2342 tests] and
      mycobacterial culture [n = 2388 tests]) and hence act as an indicator of likely
      bacterial excretion or disease progression. Badgers with the highest IFNgamma
      optical density (OD) values were most likely to subsequently test positive on
      both serological and culture tests, and this effect was detectable for up to 24
      months after the IFNgamma test. Furthermore, the higher the original IFNgamma OD
      value, the greater the chance that a badger would subsequently test positive
      using serology. Relationships between IFNgamma titres and mycobacterial culture
      results from different types of clinical sample suggest that the route of
      infection may affect the magnitude of immune response in badgers. These findings
      identify further value in the IFNgamma test as a useful research tool, as it may
      help us to target studies at animals and groups that are most likely to succumb
      to more progressive disease.

PMID- 29017618
TI  - Dissociation between affective experience and motivated behaviour in
      schizophrenia patients and their unaffected first-degree relatives and
      schizotypal individuals.
AB  - BACKGROUND: The neuropsychological origins of negative syndrome of schizophrenia
      remain elusive. Evidence from behavioural studies, which utilised emotion
      inducing pictures to elicit motivated behaviour generally reported that that
      schizophrenia patients experienced similar affective experience as healthy
      individuals but failed to translate emotional salience to motivated behaviour, a
      phenomenon called emotion-behaviour decoupling. However, a few studies have
      examined emotion-behaviour decoupling in non-psychotic high-risk populations, who
      are relatively unaffected by medication effects. METHODS: In this study, we
      examined the nature and extent of emotion-behaviour decoupling in in three
      independent samples (65 schizophrenia patients v. 63 controls; 40 unaffected
      relatives v. 45 controls; and 32 individuals with social anhedonia v. 32
      controls). We administered an experimental task to examine their affective
      experience and its coupling with behaviour, using emotion-inducing slides, and
      allowed participants to alter stimulus exposure using button-pressing to seek
      pleasure or avoid aversion. RESULTS: Schizophrenia patients reported similar
      affective experiences as their controls, while their unaffected relatives and
      individuals with high levels of social anhedonia exhibited attenuated affective
      experiences, in particular in the arousal aspect. Compared with their respective
      control groups, all of the three groups showed emotion-behaviour decoupling.
      CONCLUSIONS: Our findings support that both genetically and behaviourally high
      risk groups exhibit emotion-behaviour decoupling. The familial association
      apparently supports its role as a putative trait marker for schizophrenia.

PMID- 29017619
TI  - RELATIONSHIP BETWEEN ORPHANHOOD STATUS, LIVING ARRANGEMENTS AND SEXUAL DEBUT:
      EVIDENCE FROM FEMALES IN MIDDLE ADOLESCENCE IN SOUTHERN AFRICA.
AB  - SummaryThis study examined the relationship between orphanhood status, living
      arrangements and sexual debut. The study is important in the context of southern
      Africa, where a substantial number of children live apart from their parents
      because the parent is dead or living elsewhere, and where female adolescents face
      disproportionate sexual and reproductive health risks. Data for female
      adolescents were taken from Demographic and Health Surveys conducted in seven
      southern African countries. Unadjusted and adjusted hazard ratios of sexual debut
      were estimated using Cox Proportional Hazard models. The results from
      multivariate analyses showed that non-co-residence with biological parents was
      significantly associated with higher risk of sexual debut in five of the seven
      countries. Using pooled data, the results showed that father absence was
      associated with higher risk of sexual debut - whether the father was deceased or
      living elsewhere. Interventions to delay sexual debut among female adolescents
      should seek to promote father-adolescent co-residence and improve access to
      education.

PMID- 29017621
TI  - Challenges for bilateral pulmonary artery stenting due to occluded femoral veins.
AB  - When the inferior caval vein is occluded or abnormal, jugular and hepatic veins
      provide alternative routes for interventions. For pulmonary artery stenting,
      transhepatic access may give a relatively straighter route than that from the
      jugular veins. We describe the challenges and strategies during transhepatic
      bilateral pulmonary artery stenting after arterial switch operation complicated
      by occluded inferior caval vein and congested hepatic veins.

PMID- 29017622
TI  - Analysis of lead pollution levels within an urban ecosystem using the cestode
      Hymenolepis diminuta and its rat hosts as bioindicators.
AB  - The overall goal of this study was to use the Rattus spp./Hymenolepis diminuta
      model to assess environmental lead pollution in different landscape units of an
      urban ecosystem. Rats of the genus Rattus were collected from three shanty towns
      and three residential neighbourhoods of the city of Buenos Aires. Concentrations
      of lead in the livers of wild rats and in their parasite H. diminuta were
      measured using inductively coupled plasma mass spectrometry (ICP-MS). The
      landscape unit and tissue type had a significant effect on lead concentration,
      being higher in residential neighbourhoods as well as in H. diminuta tissue.
      Nevertheless, no significant differences were found for the mean lead
      concentration in livers between uninfected and infected rats. Since the available
      information describing heavy-metal pollution within the city of Buenos Aires is
      scarce, the results of this study allow us to update data about the extent of
      biologically available lead contamination. Considering that rats and H. diminuta
      are distributed worldwide, this monitoring system for lead pollution might be
      applied successfully in other urban ecosystems.

PMID- 29017623
TI  - The genealogy of the clinical syndrome of mania: signs and symptoms described in
      psychiatric texts from 1880 to 1900.
AB  - In 1800, mania was conceptualized as an agitated psychotic state. By 1900, it
      closely resembled its modern form. This paper reviews the descriptions of mania
      in Western psychiatry from 1880 to 1900, when Kraepelin was training and
      developing his concept of manic-depressive illness. Psychiatric textbooks
      published 1900-1960 described 22 characteristic manic symptoms/signs the presence
      of which were recorded in 25 psychiatric textbooks and three other key documents
      published 1880-1900. Descriptions of mania in these nineteenth century textbooks
      closely resembled those in the twentieth century, recording a mean (s.d.) of 15.9
      (2.3) and 17.0 (2.3) of the characteristic symptoms, respectively (p = 0.12). The
      frequency with which individual symptoms were reported was substantially
      correlated in these two periods (r = +0.64). Mendel's 1881 monograph, Kraepelin's
      first description of mania in 1883 and the entry for mania in Tuke's Dictionary
      of Psychological Medicine (1892) described a mean (s.d.) of 19 (1.7) of these
      characteristic symptoms. These descriptions of mania often contained
      phenomenologically rich descriptions of euphoria, hyperactivity, grandiosity,
      flight of ideas, and poor judgment. They also emphasized several features not in
      DSM criteria including changes in character, moral standards and physical
      appearance, and increased sense of humor and sexual drive. Fifteen authors
      described key symptoms/signs of mania most reporting elevated mood, motoric
      hyperactivity and accelerated mental processes. By 1880, the syndrome of mania
      had been largely stabilized in its modern form. In the formation of his concept
      of manic-depressive illness, Kraepelin utilized the syndrome of mania as
      described in the psychiatric community in which he was trained.

PMID- 29017624
TI  - Sociodemographic inequalities in the management of depression in adults aged 55
      and over: an analysis of English primary care data.
AB  - BACKGROUND: We do not know how primary care treatment of depression varies by age
      across both psychotropic medication and psychological therapies. METHODS: Cohort
      study including 19 710 people aged 55+ with GP recorded depression diagnoses and
      26 276 people with recorded depression symptoms during the period 2009-2013, from
      373 General Practices in The Health Improvement Network (THIN) database in
      England. Main outcomes were initiation of treatment with anti-depressants,
      anxiolytics, hypnotics, anti-psychotic drugs, referrals to psychological
      therapies within 6 months of onset. RESULTS: Treatment rates with antidepressants
      are high for those recorded with new depression diagnoses (87.1%) or symptoms of
      depression (58.7%). Treatment in those with depression diagnoses varies little by
      age. In those with depressive symptoms there was a J-shaped pattern with reduced
      antidepressant treatment in those in their 60s and 70s followed by increased
      treatment in the oldest age groups (85+ years), compared with those aged 55-59
      years. Other psychotropic drug prescribing (hypnotics/anxiolytics,
      antipsychotics) all increase with increasing age. Recorded referrals for
      psychological therapies were low, and decreased steadily with increasing age,
      such that women aged 75-79 years with depression diagnoses had around six times
      lower odds of referral (OR 0.17, 95% CI 0.1-0.29) than those aged 55-59 years,
      and men aged 80-84 years had around seven times lower (OR 0.14, 95% CI 0.05
      0.36). CONCLUSIONS: The oldest age groups with new depression diagnoses and
      symptoms have fewer recorded referrals to psychological therapies, and higher
      psychotropic drug treatment rates in primary care. This suggests potential
      inequalities in access to psychological therapies.

PMID- 29017625
TI  - Molecular data reveal high diversity of Uvulifer (Trematoda: Diplostomidae) in
      Middle America, with the description of a new species.
AB  - Members of the genus Uvulifer are distributed worldwide and infect aquatic snails
      and freshwater fishes as first and second intermediate hosts, respectively, and
      fish-eating birds (kingfishers) as definitive hosts. Metacercariae of Uvulifer
      spp. were collected from the fins and skin of 20 species of freshwater fishes in
      Mexico, Guatemala, Honduras, Nicaragua and Costa Rica, and the adults were
      recovered from the intestine of kingfishers in four localities of Mexico. The
      genetic divergence among 76 samples (64 metacercariae and 12 adults) was
      estimated by sequencing the 28S and 5.8S nuclear genes, as well as the internal
      transcribed spacers ITS1 and ITS2, and one mitochondrial gene (cox1). Maximum
      likelihood and Bayesian inference analyses inferred with each dataset showed a
      high genetic diversity within the genus Uvulifer across Middle America, revealing
      the existence of four genetic lineages that exhibit some level of host
      specificity to their second intermediate hosts. The metacercariae of lineage 1
      were associated with characids and cyprinids in central and northern Mexico.
      Metacercariae of lineages 2 and 3 were associated with cichlids distributed
      widely across Middle America. The lack of adults of these lineages in
      kingfishers, in lineages 2 and 3, or the fact that just a few adult specimens
      were recovered, as in lineage 1, prevented a formal description of these species.
      The metacercariae of lineage 4 were found in poeciliids, across a distribution
      range comprising Mexico, Guatemala, Honduras and Nicaragua, and the adult was
      found in the green kingfisher in Mexico. The number of specimens sampled for
      lineage 4, for both gravid adults and metacercariae, allowed us to describe a new
      species, Uvulifer spinatus n. sp. We describe the new species herein and we
      discuss briefly the genetic diversity in Uvulifer spp. and the importance of
      using DNA sequences to properly characterize parasite diversity.

PMID- 29017620
TI  - Familial aggregation of MATRICS Consensus Cognitive Battery scores in a large
      sample of outpatients with schizophrenia and their unaffected relatives.
AB  - BACKGROUND: The increased use of the MATRICS Consensus Cognitive Battery (MCCB)
      to investigate cognitive dysfunctions in schizophrenia fostered interest in its
      sensitivity in the context of family studies. As various measures of the same
      cognitive domains may have different power to distinguish between unaffected
      relatives of patients and controls, the relative sensitivity of MCCB tests for
      relative-control differences has to be established. We compared MCCB scores of
      852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives
      (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined
      familial aggregation of cognitive impairment by investigating within-family
      prediction of MCCB scores based on probands' scores. METHODS: Multivariate
      analysis of variance was used to analyze group differences in adjusted MCCB
      scores. Weighted least-squares analysis was used to investigate whether probands'
      MCCB scores predicted REL neurocognitive performance. RESULTS: SCZ were
      significantly impaired on all MCCB domains. REL had intermediate scores between
      SCZ and HCS, showing a similar pattern of impairment, except for social
      cognition. Proband's scores significantly predicted REL MCCB scores on all
      domains except for visual learning. CONCLUSIONS: In a large sample of stable
      patients with schizophrenia, living in the community, and in their unaffected
      relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups.
      Our findings of significant within-family prediction of MCCB scores might reflect
      disease-related genetic or environmental factors.

PMID- 29017626
TI  - Case series of mild behavioral impairment: toward an understanding of the early
      stages of neurodegenerative diseases affecting behavior and cognition.
AB  - Mild behavioral impairment (MBI) is characterized by later life acquired,
      sustained, and impactful neuropsychiatric symptoms (NPS) of any severity that
      cannot be better accounted for by other formal medical and psychiatric nosology.
      MBI is an "at risk" state for incident cognitive decline and dementia, and for
      some, MBI is the index manifestation of neurodegeneration, observed in advance of
      cognitive impairment. Initially described in Frontotemporal Dementia (FTD), MBI
      evolved to describe a preclinical stage of all cause dementia, and has been
      operationalized in the International Society to Advance Alzheimer's Research and
      Treatment-Alzheimer's Association (ISTAART-AA) proposed research diagnostic
      criteria. Here, we describe three cases in which patients diagnosed with a
      variety of dementing conditions initially presented with NPS to the Cognitive
      Neurosciences Clinic at the University of Calgary, Canada. All patients described
      in our series were given a final diagnosis of dementia; the etiology supported by
      clinical, cognitive, and neuroimaging findings. In all three cases, the
      progression to dementia was preceded by NPS that meet criteria for MBI. With
      these examples, we are able to illustrate that MBI can represent a premonitory
      stage of dementia of different etiologies. These cases demonstrate early use of
      the MBI checklist (MBI-C). The cases presented in this series serve as examples
      of NPS as early manifestations of dementia. Our case examples include both FTD
      and AD, and demonstrate that before a diagnosis of a neurodegenerative disease is
      considered, often patients will be diagnosed with and treated for a psychiatric
      condition. These early NPS can be characterized within the domains outlined in
      the ISTAART-AA MBI criteria, and detected with the MBI-C, which may help
      clinicians consider neurodegenerative disease in the differential diagnosis of
      later life onset psychiatric symptomatology.

PMID- 29017627
TI  - Mycoprotein represents a bioavailable and insulinotropic non-animal-derived
      dietary protein source: a dose-response study.
AB  - The anabolic potential of a dietary protein is determined by its ability to
      elicit postprandial rises in circulating essential amino acids and insulin.
      Minimal data exist regarding the bioavailability and insulinotropic effects of
      non-animal-derived protein sources. Mycoprotein is a sustainable and rich source
      of non-animal-derived dietary protein. We investigated the impact of mycoprotein
      ingestion, in a dose-response manner, on acute postprandial hyperaminoacidaemia
      and hyperinsulinaemia. In all, twelve healthy young men completed five
      experimental trials in a randomised, single-blind, cross-over design. During each
      trial, volunteers consumed a test drink containing either 20 g milk protein
      (MLK20) or a mass matched (not protein matched due to the fibre content) bolus of
      mycoprotein (20 g; MYC20), a protein matched bolus of mycoprotein (40 g; MYC40),
      60 g (MYC60) or 80 g (MYC80) mycoprotein. Circulating amino acid, insulin and
      uric acid concentrations, and clinical chemistry profiles, were assessed in
      arterialised venous blood samples during a 4-h postprandial period. Mycoprotein
      ingestion resulted in slower but more sustained hyperinsulinaemia and
      hyperaminoacidaemia compared with milk when protein matched, with overall
      bioavailability equivalent between conditions (P>0.05). Increasing the dose of
      mycoprotein amplified these effects, with some evidence of a plateau at 60-80 g.
      Peak postprandial leucine concentrations were 201 (sem 24) (30 min), 118 (sem 10)
      (90 min), 150 (sem 14) (90 min), 173 (sem 23) (45 min) and 201 (sem 21 (90 min)
      umol/l for MLK20, MYC20, MYC40, MYC60 and MYC80, respectively. Mycoprotein
      represents a bioavailable and insulinotropic dietary protein source.
      Consequently, mycoprotein may be a useful source of dietary protein to stimulate
      muscle protein synthesis rates.

PMID- 29017629
TI  - Potent nematicidal activity of phenolic derivatives on Meloidogyne incognita.
AB  - The present study describes the nematicidal activity of ten selected phenolic
      derivatives using the root knot nematode, Meloidogyne incognita, model.
      Nematicidal activity was then correlated with the anti-oxidant power. The highest
      nematicidal activity was recorded for p-nitrophenol followed by m-nitrophenol, o
      nitrophenol and p-bromophenol, with an EC50 after 1 day of immersion of about
      0.70 +/- 0.64, 8.14 +/- 5.49, 15.79 +/- 10.81 and 25.92 +/- 11.37 MUg/ml,
      respectively. The structure-activity relationship indicates that the nitro-group
      at position 4 on the phenolic ring (p-nitrophenol) is very important for
      nematicidal activity, followed by that at position 2 (o-nitrophenol) and position
      3 (m-nitrophenol). p-Nitrophenol showed the highest nematicidal activity with the
      corresponding lowest anti-oxidant activity of about 97 +/- 20 MUg/ml. In
      conclusion, these findings suggest that phenolic derivatives could be considered
      as potent nematicidal agents and be integrated in the pest-management system.

PMID- 29017628
TI  - Effects of microencapsulated Lactobacillus plantarum LIP-1 on the gut microbiota
      of hyperlipidaemic rats.
AB  - The in vivo effects of administering free and microencapsulated Lactobacillus
      plantarum LIP-1 cells (2.0*109 colony-forming units/d) were evaluated in high-fat
      diet-induced hyperlipidaemic rats. Results from real-time quantitative PCR
      targeting to LIP-1 cells showed a higher colon colonisation count of LIP-1 in the
      rats receiving microencapsulated cells compared with free cells (P<0.05).
      Moreover, the microencapsulated LIP-1 treatment resulted in a more obvious lipid
      lowering effect (P<0.05). Meanwhile, their faecal samples had significantly less
      lipopolysaccharide-producing bacteria (especially Bilophila, Sutterella and
      Oscillibacter) and mucosa-damaging bacteria (Bilophila and Akkermansia
      muciniphila), whereas significantly more SCFA-producing bacteria (P<0.05) (namely
      Lactobacillus, Alloprevotella, Coprococcus, Eubacterium and Ruminococcus) and
      bacteria that potentially possessed bile salt hydrolase activity (Bacteroides,
      Clostridium, Eubacterium and Lactobacillus), and other beneficial bacteria
      (Alistipes and Turicibacter). Further, Spearman's correlation analysis showed
      significant correlations between some of the modulated gut bacteria and the serum
      lipid levels. These results together confirm that microcapsulation enhanced the
      colon colonisation of LIP-1 cells, which subsequently exhibited more pronounced
      effects in improving the gut microbiota composition of hyperlipidaemic rats and
      lipid reduction.

PMID- 29017630
TI  - Poor perinatal growth impairs baboon aortic windkessel function.
AB  - The ability of the aorta to buffer blood flow and provide diastolic perfusion
      (Windkessel function) is a determinant of cardiovascular health. We have reported
      cardiac dysfunction indicating downstream vascular abnormalities in young adult
      baboons who were intrauterine growth restricted (IUGR) at birth as a result of
      moderate maternal nutrient reduction. Using 3 T MRI, we examined IUGR offspring
      (eight male, eight female; 5.7 years; human equivalent 25 years) and age-matched
      controls (eight male, eight female; 5.6 years) to quantify distal descending
      aortic cross-section (AC) and distensibility (AD). ANOVA showed decreased IUGR
      AC/body surface area (0.9+/-0.05 cm2/m2 v. 1.2+/-0.06 cm2/m2, M+/-s.e.m.,
      P<0.005) and AD (1.7+/-0.2 v. 4.0+/-0.5*10-3/mmHg, P<0.005) without sex
      difference or group-sex interaction, suggesting intrinsic vascular pathology and
      impaired development persisting in adulthood. Future studies should evaluate
      potential consequences of these changes on coronary perfusion, afterload and
      blood pressure.

PMID- 29017631
TI  - Infants born with critical CHD in Arizona and capacities of birth centres for
      screening and management.
AB  - OBJECTIVES: The aims of this study were to identify locations of births in
      Arizona with critical CHD, as well as to assess the current use of pulse-oximetry
      screening and capacities of birth centres to manage a positive screen. Study
      design Infants (n=487) with a potentially critical CHD were identified from the
      Arizona Department of Health Services from 2012 and 2013; charts were
      retrospectively reviewed. Diagnosis was confirmed using echocardiographies.
      ArcGIS was used to generate maps to visualise the location of treating facility
      and mother's residence. Birth centres were surveyed to assess screening practices
      and capacities to manage critical CHD in 2015. RESULTS: Of the 272 patients
      identified with critical CHD, 52% had been diagnosed prenatally. Patients
      travelled an average distance of 55.1 miles to their treating facility. Mortality
      was not related to prenatal diagnosis (p=0.30), living at a high elevation
      (p=0.82), or to distance travelled to the treating facility (p=0.68). Of 50 birth
      centres, 33 responded to the survey and all centres practiced critical CHD
      screening. A total of 25 centres could perform paediatric echocardiographies; 64%
      of these centres could digitally transmit echocardiograms. In all, 24 birth
      centres maintained access to prostaglandins. CONCLUSIONS: Pulse-oximetry
      screening in newborns is currently implemented in the majority of Arizona
      hospitals. Although most centres could perform initial management steps following
      a positive screen, access to paediatric cardiology services was limited. Patients
      with critical CHD sometimes travelled a great distance to treating facilities.
      Digital transmission of echocardiograms or tele-echocardiography would reduce the
      distance travelled for the management of a positive screen, decrease the
      financial burden of transportation, and expedite care for critically ill
      neonates.

PMID- 29017632
TI  - Categories, diversity, and relevance of memory strategies reported by community
      dwelling seniors.
AB  - BACKGROUND: Memory strategies help seniors remember information that is essential
      for the performance of their daily activities and contribute to their
      independence in the context of declining memory skills. This study aimed to
      analyze the categories, the diversity, and relevance of memory strategies known
      by seniors, and to identify individual characteristics that correlated with these
      variables. METHODS: The sample consisted of 294 participants aged 60 and over who
      decided to take part in a cognitive vitality promotion program. An adapted
      version of the memory situation questionnaire (Troyer, 2001) was administered to
      identify the memory strategies that seniors would use in five daily life
      situations. A scoring grid, also adapted from the questionnaire's original
      version (Troyer, 2001), was used to quantify the relevance of the strategies that
      were reported by participants. RESULTS: All participants mentioned at least once
      that they would use a strategy from the physical category of memory strategies.
      Out of a possible range of 26 strategies, participants answered an average of
      6.14 (SD = 1.7) different answers across the five situations. Based on expert
      consensus, 67.7% of the mentioned memory strategies were relevant. Diversity and
      relevance were significantly higher when trying to remember appointments, things
      to bring or phone numbers (p <= 0.05). The level of education, cognitive skills,
      and participation in leisure activities were related to diversity and relevance
      of reported strategies. CONCLUSIONS: Seniors know various and relevant memory
      strategies to perform daily activities. The advantages of integrating strategies
      that they already know in cognitive health promotion programs should be
      considered in further studies.

PMID- 29017633
TI  - Associations between maternal prenatal stress, methylation changes in IGF1 and
      IGF2, and birth weight.
AB  - Maternal stress has been linked to low birth weight in newborns. One potential
      pathway involves epigenetic changes at candidate genes that may mediate the
      effects of prenatal maternal stress on birth weight. This relationship has been
      documented in stress-related genes, such as NR3C1. There is less literature
      exploring the effect of stress on growth-related genes. IGF1 and IGF2 have been
      implicated in fetal growth and development, though via different mechanisms as
      IGF2 is under imprinting control. In this study, we tested for associations
      between prenatal stress, methylation of IGF1 and IGF2, and birth weight. A total
      of 24 mother-newborn dyads in the Democratic Republic of Congo were enrolled.
      Ethnographic interviews were conducted with mothers at delivery to gather
      culturally relevant war-related and chronic stressors. DNA methylation data were
      generated from maternal venous, cord blood and placental tissue samples.
      Multivariate regressions were used to test for associations between stress
      measures, DNA methylation and birth weight in each of the three tissue types. We
      found an association between IGF2 methylation in maternal blood and birth weight.
      Previous literature on the relationship between IGF2 methylation and birth weight
      has focused on methylation at known differentially methylated regions in cord
      blood or placental samples. Our findings indicate there may be links between the
      maternal epigenome and low birth weight that rely on mechanisms outside known
      imprinting pathways. It thus may be important to consider the effect of maternal
      exposures and epigenetic profiles on birth weight even in the setting of
      maternally imprinted genes such as IGF2.

PMID- 29017634
TI  - Factors Influencing New RNs' Supervisory Performance in Long-Term Care
      Facilities.
AB  - In long-term care facilities (LTCF), registered nurses (RNs) perform both
      clinical and supervisory roles as part of a team aiming to provide high-quality
      care to residents. The residents have several co-morbidities and complex care
      needs. Unfortunately, new RNs receive minimal preparation in gerontology and
      supervisory experience during their program, leading to low retention rates and
      affecting resident outcomes. This qualitative study explored factors that
      influence supervisory performance of new RNs in LTCF from the perspective of 24
      participants from Ontario, Canada. Data were collected through individual
      interviews, followed by a directed content analysis. Three levels of influences
      were identified: personal influences, organizational influences, and external
      influences. Each level presented with sub-elements, further describing the
      factors that impact the supervisory performance of the new RN. To retain new RNs
      in LTC, organizations must provide additional gerontological education and
      mentoring for new RNs to flourish in their supervisory roles.

PMID- 29017635
TI  - Hymenolepis diminuta and Rodentolepis nana (Hymenolepididae: Cyclophyllidea) in
      urban rodents of Gran La Plata: association with socio-environmental conditions.
AB  - The aim of this survey was to study two Hymenolepididae species in urban rodents,
      Rattus rattus and Rattus norvegicus, and to analyse factors that favour their
      presence in the environment and pose a sanitary risk. Hymenolepis diminuta and
      Rodentolepis nana were found in R. rattus and R. norvegicus in different
      proportions. Values of prevalence, mean abundance and mean intensity were
      recorded, and new morphometric characters were described, adding to previously
      known information. No significant differences were found. However, the results
      revealed that there is a tendency for these parasites to develop in areas with
      deficient socio-structural conditions and in water bodies. This study thereby
      shows that certain areas on the periphery of the Gran La Plata favour the
      existence of rodents, which act as sentinels of zoonotic diseases, and stresses
      the need to take action to minimize them in order to avoid putting human and
      animal health at risk.

PMID- 29017636
TI  - Psychometric Properties of the Lifetime Assessment of Violent Acts.
AB  - The Lifetime Assessment of Violent Acts (LAVA) inventory provides estimates of
      the frequency, triggers, and consequences (including injuries to others) of
      historic acts of aggression. The LAVA also identifies the situational contexts in
      which prior violence was triggered and allows classifications based on past
      reactive, intimate partner, alcoholrelated, and/or weapon-related violence.
      Normative and psychometric data were provided from a college (N = 1,133) and
      general population (N = 545) sample. Around 15% of the general population sample
      recalled inflicting 5 or more injuries on others at some time in the past. LAVA
      scores were significantly higher for women than men (d = .45), and respondents
      from the general population were more aggressive than those in the college sample
      (d = .41). The potential benefits, applications, and limitations of this
      retrospective self-report inventory are discussed.

PMID- 29017637
TI  - Intimate Terrorism and Situational Couple Violence: Classification Variability
      Across Five Methods to Distinguish Johnson's Violent Relationship Types.
AB  - Johnson's (1995, 2008) theory of violent relationship types represents an
      opportunity to resolve debates surrounding intimate partner violence (IPV)
      prevalence and to adapt policy and treatment options for victims accordingly.
      However, the use of quantitative methods to distinguish between situational
      couple violence (SCV) and intimate terrorism (IT) remains in its initial stages
      of discovery. This study included a 2-phase (N = 840; via targeted community and
      agency sampling) online survey design comparing the utility and grouping
      variability across 5 methods of IT/SCV classification: victimization-variables
      and coercive-control-variable hierarchical clustering, vignette-choice, cutoff
      scoring, and expert coding. Findings are discussed in terms of contributions to
      differing IPV-research perspectives, researchers' understanding of existing
      classification methods, and practitioners' awareness of victims' voices in
      quantitative research.

PMID- 29017638
TI  - The Difference Between Living and Dying: Victim Characteristics and Motive Among
      Nonfatal Shootings and Gun Homicides.
AB  - Using both official and unofficial data sources, researchers examined nonfatal (n
      = 617) and fatal shooting (n = 159) victim characteristics over an 18-month
      period in Indianapolis. This research revealed that the typical shooting victim
      was male, non-White, almost 29 years old, had been arrested prior to inclusion in
      this study, and had been shot more than once. Interestingly, this research
      supports the notion that nonfatal shooting and homicide victims are different,
      especially as they relate to victim age, gunshot wound severity, and shooting
      motive. It highlights the need for better gun violence data collection beyond
      what currently exists. Striving for improved, more comprehensive cross-sector
      data collection has implications beyond just police policy and practice to
      include public health and prevention efforts.

PMID- 29017639
TI  - Predicting Grief Reactions One Year Following a Mass University Shooting:
      Evaluating Dose-Response and Contextual Predictors.
AB  - This study identifies risk factors for grief following a mass school shooting.
      Participants (N = 1,013) completed online questionnaires 3-4 months (Time 1) and
      1 year (Time 2) post-shootings. We tested models predicting Time 2 grief
      reactions, exploring direct and indirect predictive effects of exposure variables
      (physical and social proximity) through hypothesized peritraumatic mediators
      (peritraumatic perceived threat to self or others) while controlling for Time 1
      grief and posttraumatic stress (PTS) reactions, pretrauma vulnerabilities.
      Findings demonstrate that closer social proximity predicted higher levels of Time
      2 grief, directly and indirectly through increasing peritraumatic perceived
      threat to others' safety. Physical proximity and peritraumatic threat to self did
      not predict Time 2 grief reactions. Implications for grief screening instruments
      and theory building research through identifying risk factors and causal
      mechanisms are discussed.

PMID- 29017640
TI  - Investigating the Risk of Date Rape by Auditory Status.
AB  - This exploratory study examines the impact of auditory status, gender, and prior
      sexual victimization on attitudes and behaviors related to date rape among
      undergraduate college students (n = 3,352) at a private university in the
      northeast. An abbreviated version of the College Date Rape Attitude and Behavior
      Survey (Lanier & Elliot, 1997) and the Sexual Experiences Survey (Koss, Gidycz, &
      Wisniewski, 1987) were employed. Findings indicated that Deaf and hard of hearing
      (DHH) students were more likely to experience negative sexual experiences than
      hearing students. No differences were found in rape-supportive attitudes by
      auditory status. The analysis also found that DHH students were more likely to
      engage in sexual behaviors that increase the risk of date rape than were hearing
      students. Finally, significant differences were found regarding gender and prior
      sexual victimization on rape attitudes and behaviors. Implications and directions
      for future research are discussed.

PMID- 29017641
TI  - Family Matters: Examining Child Abuse and Neglect as Family Dysfunction for
      Minority Youth Living in Extreme Poverty.
AB  - Two competing models of child abuse and neglect (scapegoat vs. family
      dysfunction) are used to illustrate how the specification of victims ("index"
      victim vs. all children in household) from incidents of child abuse and neglect
      can be used to improve estimates of maltreatment for at-risk minority youth.
      Child Protection Services records were searched in 2005 for 366 "index" victims
      who were surveyed for 5 consecutive years (from 1998 to 2002) for the Mobile
      Youth Survey as well as other siblings in the household. The findings indicate
      that the baseline estimate of any maltreatment, sexual abuse, physical abuse, and
      neglect increased by 68%, 26%, 33%, and 74%, respectively, after adjusting for
      incidents that involved multiple victims (i.e., maltreatment as family
      dysfunction). In addition, the baseline estimate of more severe (indicated)
      incidents of physical abuse and neglect increased by 67% and 64%, respectively,
      after accounting for incidents that involved multiple victims, but there were no
      incidents of more severe (indicated) sexual abuse that involved multiple victims.
      Similarly, baseline estimates of age of onset (or chronicity) of maltreatment
      during childhood and adolescence increased by 62% and 26%, respectively. Baseline
      estimates for youth with 3 or more years of maltreatment and youth with 3 or more
      incidents of maltreatment both increased by about 71%. The implications of these
      findings for policy and practice as well as areas for future research are also
      discussed.

PMID- 29017642
TI  - Random Acts of Violence? Examining Probabilistic Independence of the Temporal
      Distribution of Mass Killing Events in the United States.
AB  - Recent mass killings, such as those in Newtown, Connecticut, and Aurora,
      Colorado, have brought new attention to mass killings in the United States. This
      article examines 323 mass killings taking place between January 1, 2006, and
      October 4, 2016, to assess how they are distributed over time. In particular, we
      find that they appear to be uniformly distributed over time, which suggests that
      their rate has remained stable over the past decade. Moreover, analysis of
      subsets of these mass killings sharing a common trait (e.g., family killings,
      public killings) suggests that they exhibit a memoryless property, suggesting
      that mass killing events within each category are random in the sense that the
      occurrence of a mass killing event does not signal whether another mass killing
      event is imminent. However, the same memoryless property is not found when
      combining all mass killings into a single analysis, consistent with earlier
      research that found evidence of a contagion effect among mass killing events.
      Because of the temporal randomness of public mass killings and the wide
      geographic area over which they can occur, these results imply that these events
      may be best addressed by systemic infrastructure-based interventions that deter
      such events, incorporate resiliency into the response system, or impede such
      events until law enforcement can respond when they do occur.

PMID- 29017643
TI  - [Chinese consensus on CPR and American guidelines on CPR].
AB  - OBJECTIVE: In the article, we compared "2016 national consensus on
      cardiopulmonary resuscitation in China" and "2015 American Heart Association
      guidelines on cardiopulmonary resuscitation and emergency cardiovascular care"
      with their definition, orientation, characterization, quantifying and thinking
      mode. Chinese consensus on cardiopulmonary resuscitation (CPR) emphasizes the
      concept of "survival cycle" and focuses on the victim, it defines the rate of
      survival in its broad sense, and the thinking mode of the document is typically
      oriental style. However, American guidelines on CPR emphasize the concept of
      "survival chain" and the rescuer, it defines the rate of survival in its narrow
      sense, and the thinking mode is western style. The Chinese consensus cited
      American guidelines as part of references, and specialized them locally according
      to the current situation in China. In Chinese consensus, the cycle of survival
      covers three periods, pre-arrest phase, intra-arrest phase and post-resuscitation
      phase. In the pre-arrest phase, "three-prevention" policies should be adopted,
      which are precaution, pre-identification and early warning. During intra-arrest
      phase, CPR should be carried out with "three-ways" strategies, which are
      standardization, diversification and individuation. The "three lives" general
      plans should be considered during the post-resuscitation phase, which are
      demutation, transcending and extension. Chinese consensus on CPR has provided an
      omnibearing, overall-process and three-dimensional program with Chinese wisdom.

PMID- 29017644
TI  - [Analysis of out-of-hospital emergency treatment for ventricular fibrillation
      between 2013 and 2016 in Shanghai].
AB  - OBJECTIVE: To investigate the epidemiological features of out-of-hospital
      patients with ventricular fibrillation (VF) in Shanghai and to analysis factors
      associated with outcomes, and to provide evidence for improving the success rate
      of VF. METHODS: The data of patients with VF admitted to Shanghai Medical
      Emergency Center from January 2013 to December 2016 were analyzed
      retrospectively. All the data were recorded including the clinical data, medical
      service time, return of spontaneous circulation (ROSC) at scene/en route,
      survival to hospital discharge. Factors that associated with successful
      resuscitation were analyzed by Logistic regression. RESULTS: From 2013 to 2016,
      21 096 patients with suspected cardiac arrest were admitted to the Shanghai
      Medical Emergency Center. After excluding ventricular tachycardia (13 cases) and
      ventricular asystole (20 995 cases), 88 patients with VF were enrolled, with 62
      male and 26 female; the average age was (63.22+/-16.15) years old. While
      bystander cardiopulmonary resuscitation (CPR) was performed in only 21 cases
      (23.86%). Fifty-seven cases occurred during the day (08:00-20:00), while 31 cases
      occurred in the night. And the average emergency response time was (6.47+/-4.13)
      minutes; the average on-site time was (14.76+/-10.88) minutes; the average
      transport to hospital time was (5.95+/-4.00) minutes. There were no significant
      differences in response time, on-site time and transport to hospital time each
      year, and there were no significant differences in emergency medical service time
      between day and night either. From 2013 to 2016, prehospital successful
      resuscitation rate was decreased by years [95.65% (22/23), 87.50% (14/16), 83.33%
      (20/24) vs. 80.00% (20/25), respectively, chi2 = 1.895, P = 0.595]. Survival to
      hospital discharge rate was increased by years [21.74% (5/23), 31.25% (5/16),
      37.50% (9/24), 40.00% (10/25), respectively, chi 2 = 2.862, P = 0.413]. The
      success rate of prehospital resuscitation for patients with 1, 2, >=3
      defibrillation was 35.23% (31/88), 23.08% (12/52), 89.19% (33/37), respectively
      (chi2 = 42.811, P = 0.000). The on-site time in successful final resuscitation
      group was shorter than that in final resuscitation failure group (minutes:
      10.85+/-8.83 vs. 16.79+/-11.36, t = 2.367, P = 0.020), the ROSC time in
      successful final resuscitation group was shorter than that of final resuscitation
      failure group (minutes: 3.24+/-3.17 vs. 7.43+/-6.64, t = 3.175, P = 0.002). It
      was shown by Logistic regression that long ROSC time was the risk factor for
      final resuscitation failure [odds ratio (OR) = 0.771, P = 0.024]. Gender, age,
      availability of witnesses CPR, call time, emergency response time, on-site time
      and transport to hospital time had no significant impact on the prehospital
      successful resuscitation and final successful resuscitation. In prehospital
      successful resuscitation group, there was significant difference in survival to
      hospital discharge rate among different defibrillation times group [48.39%
      (15/31), 58.33% (7/12) vs. 21.21% (7/33), chi2 = 7.460, P = 0.024]. CONCLUSIONS:
      From 2013 to 2016, there were no significant changes in the emergency response
      time, prehospital successful resuscitation rate and survival to hospital
      discharge rate of patients with VF in Shanghai. Though, repeated defibrillation
      could significantly increased prehospital successful resuscitation rate, multiple
      defibrillation indicated decline of survival to hospital discharge rate in
      prehospital successful resuscitation group. Additionally, long on-site time and
      long ROSC time indicated poor prognosis.

PMID- 29017645
TI  - [Effect of regional synergistic treatment system on the treatment time and short
      term prognosis of ST-segment elevation myocardial infarction].
AB  - OBJECTIVE: To explore the effect of regional synergistic treatment system on the
      treatment time and short-term prognosis of patients with ST-segment elevation
      myocardial infarction (STEMI). METHODS: A retrospective analysis of the clinical
      data of STEMI patients who admitted to emergency center of Suzhou Kowloon
      Hospital Affiliated to Shanghai Jiaotong University School of Medicine and
      underwent primary percutaneous coronary intervention (PPCI) from January 2013 to
      January 2017 were conducted. All patients were divided into two groups, group A
      was the patients who underwent the PPCI before the establishment of the acute
      chest pain area co-treatment system (from January 2013 to December 2014), and
      group B was the patients who received the treatment after the establishment of
      the area co-treatment system (from January 2015 to January 2017). The length of
      time from onset of symptoms to the balloon dilatation (S2B), the length of time
      from the first medical contact to the balloon dilatation (FMC2B), the length of
      time from entering the gate of hospital to the balloon dilatation (D2B), and the
      incidence of 90-day end point events (including heart failure, all-cause death,
      and other related adverse events) were collected. The relations of the
      establishment of the acute chest pain area co-treatment system and the incidence
      of 90-day end point events were analyzed by multivariable Logistic regression
      analysis. RESULTS: Among the 221 enrolled patients with STEMI, 83 patients were
      in group A and 138 patients were in group B respectively. Compared with group A,
      S2B time [minutes: 180 (140, 210) vs. 201 (154, 225)], FMC2B time [minutes: 89
      (78, 100) vs. 94 (83, 107)] and D2B time [minutes: 66 (62, 70) vs. 85 (72, 99)]
      were significantly shortened in group B (all P < 0.05), the incidence of 90-day
      end point events were significantly decreased (heart failure: 20.3% vs. 32.5%,
      all-cause death: 1.4% vs. 7.2%, other related adverse events: 23.2% vs. 36.1%,
      all P < 0.05). It was shown by multivariable Logistic regression analysis that
      the establishment of the acute chest pain area co-treatment system could lower
      the incidence of 90-day end point events [heart failure: odds ratio (OR) = 1.904,
      95% confidence interval (95%CI) = 0.968-1.004, P = 0.048; all-cause death: OR =
      11.724, 95%CI = 0.955-1.048, P = 0.013; other related adverse events: OR = 1.925,
      95%CI = 1.049-3.530, P = 0.034]. CONCLUSIONS: The construction of regional
      synergistic treatment system can shorten the emergency treatment time of STEMI
      patients and reduce the incidence of 90-day end point events including heart
      failure and death.

PMID- 29017646
TI  - [Pre-hospital therapeutic hypothermia for survival and neuro-protection after out
      of-hospital cardiac arrest: a systematic review and Meta-analysis of randomized
      controlled trials].
AB  - OBJECTIVE: To assess the effectiveness of pre-hospital therapeutic hypothermia
      after out-of-hospital cardiac arrest (OHCA) for survival and neuro-protection.
      METHODS: Databases such as Medline, ScienceDirect, Embase, Highwire, Cochrane
      Library, CNKI and Wanfang digital database were searched from January 2000 to
      March 2017 to retrieve randomized controlled trials (RCTs) on pre-hospital
      therapeutic hypothermia after OHCA. Thereafter, the studies retrieved were
      screened based on predefined inclusion and exclusion criteria. Data were
      extracted and the quality of the included studies was evaluated. A Meta-analysis
      was performed using the Cochrane Collaboration RevMan 4.3 software. Analysis of
      publication bias was depicted by funnel plot. RESULTS: Eight studies involving 3
      555 cases were included, among which 1 804 cases were assigned to the treatment
      group and 1 751 cases to the control group. Meta-analysis showed that compared
      with in-hospital therapeutic hypothermia, pre-hospital therapeutic hypothermia
      did not improve the survival rate of patients with OHCA [odds ratio (OR) = 1.00,
      95% confidence interval (95%CI) = 0.85-1.18, P = 0.99], and neurological outcome
      at hospital discharge (OR = 0.97, 95%CI = 0.80-1.16, P = 0.71), but the body
      temperature was significantly lowered at admission [weighted mean difference
      (SMD) = -0.88, 95%CI = -1.03 to -0.73, P < 0.000 01]. The funnel plot suggested
      that there was no publication bias in the 8 studies. But due to the low number of
      studies, the publication bias could not be completely excluded. CONCLUSIONS: Pre
      hospital therapeutic hypothermia after OHCA can decrease temperature at hospital
      admission, but cannot increase the survival rate and neurological outcome at
      hospital discharge.

PMID- 29017647
TI  - [Early evaluation of patients with amplitude-integrated electroencephalogram on
      brain function prognosis after cardiopulmonary cerebral resuscitation].
AB  - OBJECTIVE: To explore the characteristic of early evaluation of patients with
      amplitude-integrated electroencephalogram (aEEG) on brain function prognosis
      after cardiopulmonary cerebral resuscitation (CPCR). METHODS: A retrospective
      analysis of the clinical data of patients with adult CPCR in intensive care unit
      (ICU) of Henan Provincial People's Hospital from March 2016 to March 2017 was
      performed. The length of stay, recovery time, acute physiology and chronic health
      evaluation II (APACHE II) score, aEEG and Glasgow coma scale (GCS) within 72
      hours were recorded. The main clinical outcome was the prognosis of brain
      function (Glasgow-Pittsburgh cerebral performance category, CPC) in patients with
      CPCR after 3 months. Relationship between aEEG and GCS and their correlation with
      brain function prognosis was analyzed by Spearman rank correlation analysis. The
      effects of aEEG and GCS on prognosis of brain function were evaluated by Logistic
      regression analysis. The predictive ability of aEEG and GCS for brain function
      prognosis was evaluated by receiver operating characteristic (ROC) curve.
      RESULTS: A total of 31 patients with CPCR were enrolled, with 18 males and 13
      females; mean age was (41.84+/-16.96) years old; recovery time average was
      (19.42+/-10.79) minutes; the length of stay was (14.84+/-10.86) days; APACHE II
      score 19.29+/-6.42; aEEG grade I (normal amplitude) in 7 cases, grade II (mild to
      moderate abnormal amplitude) in 13 cases, grade III (severe abnormal amplitude)
      in 11 cases; GCS grade I (9-14 scores) in 7 cases, grade II (4-8 scores) in 14
      cases, grade III (3 scores) in 10 cases; 19 survivals, 12 deaths; the prognosis
      of brain function was good (CPC 1-2) in 8 cases, and the prognosis of brain
      function was poor (CPC 3-5) in 23 cases. There was no significant difference in
      age, gender, recovery time, length of stay and APACHE II score between two groups
      with different brain function prognosis, while aEEG grade and GCS grade were
      significantly different. Cochran-Armitage trend test showed that the higher the
      grade of aEEG and GCS, the worse the prognosis of CPCR patients (both P-trend <
      0.01). With the increase in GCS classification, the classification of aEEG was
      also increasing (r = 0.620 6, P = 0.000 3). Both aEEG and GCS were positively
      correlated with the prognosis of brain function (r1 = 0.779 6, P1 < 0.000 1; r2 =
      0.702 1, P2 < 0.000 1). Univariate Logistic regression analysis showed that aEEG
      and GCS had significant effect on early brain function prognosis [aEEG: odds
      ratio (OR) = 37.234, 95% confidence interval (95%CI) = 3.168-437.652, P = 0.004,
      GCS: OR = 12.333, 95%CI = 1.992-76.352, P = 0.007]; after adjusting for aEEG and
      GCS, only aEEG had significant effect on the early prognosis of brain function
      (OR = 26.932, 95%CI = 1.729-419.471, P = 0.019). The ROC curve analysis showed
      that in the evaluation of the prognosis of CPCR patients with brain function, the
      area under ROC curve (AUC) of aEEG was 0.913, when the cut-off value of aEEG was
      1.5, the sensitivity was 95.7% and the specificity was 75.0%. The AUC of GCS was
      0.851, the best cut-off value was 1.5, the sensitivity was 91.3% and the
      specificity was 62.5%. CONCLUSIONS: aEEG and GCS scores have a good correlation
      in the evaluation of brain function prognosis in patients with CPCR, the accuracy
      of aEEG in the early evaluation of the prognosis of patients with CPCR is higher
      than the GCS score.

PMID- 29017648
TI  - [Neurological prognostic value of gray-white-matter ratio in patients after
      respiratory and cardiac arrest].
AB  - OBJECTIVE: To evaluate the role of gray-white-matter ratio (GWR) on neurological
      outcome in patients with coma after cardiopulmonary resuscitation (CPR) post
      respiratory and cardiac arrest (CA). METHODS: Respiratory and CA patients with
      restoration of spontaneous circulation (ROSC) and coma after CPR admitted to
      Nanjing Drum Tower Hospital Clinical Medical College of Nanjing Medical
      University from February 2013 to June 2016 were enrolled. All patients were
      subjected to target temperature management (TTM) after CPR, and received cranial
      CT within 5 days after ROSC. Attenuation (hounsfield units) was measured at
      special sites (basal ganglia, centrum semiovale), and specific locus (caudate
      nucleus, put amen, corpus callosum, posterior limb of internal capsule, medial
      cortex, medial white matter). The GWR was calculated for basal ganglia and
      cerebrum. Neurological outcome was judged according to the Glasgow-Pittsburgh
      cerebral performance category (CPC) at 3 months after ICU discharge. CPC 1-3 were
      divided into good prognosis, CPC 4-5 were divided into poor prognosis. The
      receiver-operating characteristic (ROC) curve was drawn to evaluate the
      prognostic value of GWR in patients with respiratory and CA. RESULTS: Forty-three
      patients were enrolled, including 26 males and 17 females; age (63+/-15) years
      old; 14 good prognosis and 29 poor prognosis. Compared with the good prognosis
      group, the basal ganglia GWR (GWRbg) and the average GWR (GWRav) were
      significantly lowered in the poor prognosis group (1.064+/-0.103 vs. 1.163+/
      0.818, 1.068+/-0.087 vs. 1.128+/-0.071, both P < 0.05), the centrum semiovale GWR
      (GWRce) was similar to that in the good prognosis group (1.072+/-0.077 vs.
      1.092+/-0.075, P > 0.05). It was shown by ROC curve analysis that the GWRbg,
      GWRav could evaluate the neurological outcomes of patients, but GWRce could not.
      The area under the ROC curve (AUC) of GWRbg was 0.756 [95% confidence interval
      (95%CI) = 0.607-0.905, P = 0.007], the cut-off value was 1.13, the sensitivity
      was 71.4%, and specificity was 69.0%; the AUC of GWRav was 0.701 (95%CI = 0.532
      0.869, P = 0.035), the cut-off value was 1.13, the sensitivity was 71.4%, and
      specificity was 65.5%; the AUC of GWRce was 0.590 (95%CI = 0.405-0.775, P =
      0.344). CONCLUSIONS: Respiratory and CA patients receiving TTM with high GWR had
      favorable neurological outcome. GWR, especially GWRbg could provide help for
      clinical treatment and prognostic value of survival after CA.

PMID- 29017649
TI  - [Usefulness of procalcitonin for the diagnosis of infection in cardiac surgical
      patients].
AB  - OBJECTIVE: To determine the value of procalcitonin (PCT) as an early marker of
      postoperative infection after cardiac surgery with cardiopulmonary bypass (CPB).
      METHODS: A retrospective study was conducted. Patients with systemic inflammatory
      response syndrome (SIRS) after cardiac surgery with CPB admitted to intensive
      care unit (ICU) of Peking Union Medical College Hospital from November 2014 to
      January 2017 were enrolled. The cardiac surgery types and intraoperative
      conditions, the treatments in ICU, postoperative 28-day mortality and hospital
      mortality of the patients; the levels of plasma PCT measured at ICU admission,
      postoperative 1, 3, and 5 days were collected. According to whether patients with
      postoperative infection or not, they were divided into infection group and non
      infection group. Receiver operating characteristic curve (ROC) was used to
      analyze the predictive value of plasma PCT levels at different time points in
      patients with infection. RESULTS: Eighty-two patients were included in this
      study, 25 (30.5%) had microbiological evidence of pneumonia. The levels of plasma
      PCT were increased with a peak 1 day after cardiac surgery in all patients, then
      significantly decreased 5 days after operation. Compared with patients without
      infection, the levels of plasma PCT were significantly increased in patients with
      infection at immediate and 1, 3, 5 days post operation in ICU [MUg/L: 10.0 (6.0,
      64.5) vs. 5.0 (1.0, 10.0), 31.0 (10.0, 116.2) vs. 5.0 (1.0, 10.0), 34.7 (10.0,
      60.4) vs. 2.9 (0.7, 9.3), 15.8 (7.7, 29.4) vs. 0.7 (0.5, 2.6), all P < 0.01]. The
      area under the ROC curve (AUC) of the plasma PCT levels at ICU admission, and 1,
      3, 5 days thereafter to predict infection for critically ill patients with SIRS
      after CPB was 0.77, 0.82, 0.86, and 0.91, respectively (all P < 0.01), cut-off
      values were 6.8, 9.4, 9.2 and 3.9 MUg/L, with the sensitivities of 76.0%, 84.0%,
      79.2%, and 88.0%, and the specificities of 66.7%, 68.4%, 75.4%, and 78.9%,
      respectively. CONCLUSIONS: In the presence of SIRS, elevated plasma PCT levels
      correlated with evidence of infection in early stage post operation in the ICU
      patients after cardiac surgery with use of CPB. The level of plasma PCT exceeded
      the cut-off value in different time points, suggesting infection, and it is
      helpful to predict the occurrence of infection early after operation.

PMID- 29017650
TI  - [Effect of dynamin-related protein 1 in rats with myocardial ischemia/reperfusion
      injury].
AB  - OBJECTIVE: To investigate the protective effect of dynamin-related protein 1
      (Drp1) in rats with myocardial ischemia/reperfusion injury (IRI). METHODS: Twenty
      four healthy male Wistar rats were randomly divided into three groups (n = 8
      each): sham group, IRI model group, and Drp1 inhibitor group. The left anterior
      descending branch of coronary artery was ligated to produce myocardial ischemia
      for 30 minutes and reperfusion injury model. Sham group was received only
      threading without ligation. The Drp1 inhibitor group was injected with 1.2 mg/kg
      mitochondrial division inhibitor 1 (mdivi-1) at 15 minutes before operation. At 3
      hours after reperfusion, hemodynamics, serum myocardial enzymes, mitochondrial
      membrane potential (MMP), hydrogen peroxide (H2O2), reactive oxygen species (ROS)
      and ATP production were measured in rats. The myocardial tissues were harvested
      for the determination of the area at risk (AAR) and the infarct area (AI), and
      the ratio of AI/AAR was calculated. The expression of Drp1 and cytochrome C (Cyt
      C) was determined by Western Blot. RESULTS: Compared with the sham group, the
      left ventricular end diastolic pressure (LVEDP), cardiac troponin I (cTnI), MB
      isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH), AI/AAR, H2O2,
      ROS, protein expression of Drp1 and Cyt C were significantly increased, left
      ventricular end systolic pressure (LVESP), ejection fraction (EF), fractional
      shortening (FS), MMP, ATP generation, expression of mitochondrial Cyt C were
      significantly decreased in IRI model group. Compared with IRI model group, LVEDP
      was significantly decreased in Drp1 inhibitor group [mmHg (1 mmHg = 0.133 kPa):
      8.83+/-1.20 vs. 16.48+/-1.80], LVESP, EF, FS were significantly increased [LVESP
      (mmHg): 116.80+/-9.78 vs. 87.80+/-8.82, EF: 0.78+/-0.11 vs. 0.58+/-0.07, FS:
      (48.6+/-4.1)% vs. (32.4+/-3.2)%]; myocardial enzymes, H2O2 and ROS were
      significantly decreased in Drp1 inhibitor group [cTnI (ng/L): 31.9+/-8.8 vs.
      49.2+/-13.7, CK-MB (U/L): 4.83+/-1.30 vs. 7.48+/-2.20, LDH (U/L): 1 327.80+/
      280.20 vs. 1 858.80+/-324.80, H2O2: 6.40+/-1.40 vs. 8.90+/-1.50, ROS: 41 916.3+/
      6 295.3 vs. 65 182.6+/-3 777.8], AI/AAR was significantly decreased (0.38+/-0.01
      vs. 0.62+/-0.01), MMP and ATP were significantly increased [MMP: 0.78+/-0.13 vs.
      0.38+/-0.07, ATP (MUmol/g): 150.8+/-12.3 vs. 103.7+/-8.4], the expression of Drp1
      was significantly decreased (0.50+/-0.02 vs. 0.79+/-0.05), expression of
      mitochondria Cyt C was significantly increased (0.64+/-0.04 vs. 0.21+/-0.01), and
      expression of cytoplasmic Cyt C was significantly decreased (0.48+/-0.03 vs.
      0.78+/-0.04), and the differences were statistically significant (all P < 0.05).
      CONCLUSIONS: Mitochondrial fission was excessively high during IRI, and its
      function was significantly decreased. Drp1 inhibitor could inhibit the division
      of mitochondria, and improve its function and cardiac function.

PMID- 29017651
TI  - [Influence of Rhubarb extract on the expression of NGAL and IL-18 in the kidney
      of rabbits after CPR].
AB  - OBJECTIVE: To study the preventive effect and mechanism of Rhubarb extract on
      renal injury after cardiopulmonary resuscitation (CPR) in rabbits with cardiac
      arrest (CA). METHODS: Twenty-four male Japanese big-ear rabbits were divided into
      sham operation group, CPR model group and Rhubarb pretreatment group by random
      number table method, with 8 rabbits in each group. The rabbits in Rhubarb
      pretreatment group were treated with Rhubarb extract 5 mL*kg-1*d-1 for 7 days;
      and those in sham operation group and CPR model group were fed with 0.9% normal
      saline 10 mL/d for 7 days. After 7 days, ventricular fibrillation (VF) was
      produced in CPR model group and Rhubarb pretreatment group by 50 V alternating
      currents stimulation through bottom of the heart leads to the apex to prepare CPR
      model. The rabbits of the CPR model group and Rhubarb pretreatment group were
      sacrificed at 2 hours after successful resuscitation, and the animals in the sham
      operated group were sacrificed directly after anesthesia. The levers of blood
      urea nitrogen (BUN) and creatinine (Cr) in serum were examined by automatic
      biochemical analyzer. The positive expression area of neutrophil gelatinase
      associated lipocalin (NGAL) and interleukin-18 (IL-18) in kidney were examined by
      immunohistochemistry. RESULTS: Compared with the sham operation group, the levels
      of BUN and Cr were significantly increased in the CPR model group and Rhubarb
      pretreatment group [BUN (mmol/L): 15.53+/-3.90, 10.51+/-3.16 vs. 7.03+/-2.23, Cr
      (MUmol/L): 137.20+/-12.23, 86.80+/-7.67 vs. 66.39+/-5.47, both P < 0.05].
      Compared with the CPR model group, the levels of BUN and Cr were significantly
      decreased in the Rhubarb pretreatment group [BUN (mmol/L): 10.51+/-3.16 vs.
      15.53+/-3.90, Cr (MUmol/L): 86.80+/-7.67 vs. 137.20+/-12.23, both P < 0.05].
      Immunohistochemical staining showed that the expression of NGAL and IL-18 mainly
      existed in glomerular and tubular cells in patina. Compared with the sham
      operation group, the positive expression areas of NGAL and IL-18 in kidney were
      significantly increased in the CPR model group and Rhubarb pretreatment group
      [NGAL (MUm2): 208.26+/-7.58, 136.74+/-5.33 vs. 98.93+/-7.83, IL-18 (MUm2):
      256.48+/-4.64, 113.22+/-6.98 vs. 77.06+/-6.47, all P < 0.05]. Compared with the
      CPR model group, the positive expression areas of NGAL and IL-18 were
      significantly decreased in the Rhubarb pretreatment group [NGAL (MUm2): 136.74+/
      5.33 vs. 208.26+/-7.58, IL-18 (MUm2): 113.22+/-6.98 vs. 256.48+/-4.64, both P <
      0.05]. CONCLUSIONS: CA can lead to acute kidney injury (AKI). Rhubarb extract can
      reduce the expression of NGAL and IL-18 in kidney of rabbits after CPR, and
      protect the kidney after CPR.

PMID- 29017652
TI  - [Hydrogen can alleviate post-cardiac arrest myocardium injury in rabbits].
AB  - OBJECTIVE: To investigate the effects of hydrogen (H2) on myocardium injury post
      cardiac arrest (CA) in rabbits. METHODS: Sixty New Zealand rabbits were randomly
      divided into H2 treatment group (n = 30) and control group (n = 30) by random
      number table. The rabbit CA model was established by means of electrical
      stimulation of external membrane, both groups were mechanically ventilated.
      Cardiopulmonary resuscitation (CPR) was performed after 6 minutes of
      nonintervention, and stopped after restoration of spontaneous circulation (ROSC).
      Inhalation of 2% H2 gas was conferred to rabbits immediately at the end of CA
      modeling for 72 hours in H2 treatment group. Air was given to rabbits in control
      group instead. The survival rate of rabbits was analyzed. Heart rate, ventricular
      premature beat frequency, and the levels of blood samples cardiac troponin I
      (cTnI), left ventricular ejection fraction (LVEF), B-type natriuretic peptide
      (BNP), and blood lactic acid (Lac) were collected before CA and after ROSC in all
      rabbits. Rabbits were sacrificed and microstructure injury was observed by
      electric microscope after ROSC 72 hours. RESULTS: There were 28 animals ROSC in
      both groups; the survival number in H2 treatment group was higher than that in
      control group at 72 hours after ROSC (number: 15 vs. 7, chi2 = 4.791, P = 0.029).
      In the early stage of ROSC, the heart rate of two groups slowed down, the number
      of premature ventricular increased, and then gradually recovered; the heart rate
      in H2 treatment group was returning to normal more quickly than that in control
      group at 48 hours after ROSC (bpm: 319+/-63 vs. 362+/-40, P < 0.05); the
      ventricular premature beat frequency was lower than that in control group at 72
      hours after ROSC (times per minutes: 9.1+/-4.3 vs. 15.0+/-8.0, P < 0.05). The
      animals of two groups had different degrees of myocardial damage and cardiac
      insufficiency after ROSC, and restored with the extension of time. Compared with
      control group, the level of BNP in H2 treatment group was significant decreased
      at 24 hours after ROSC (ng/L: 385+/-98 vs. 488+/-174, P < 0.05), the levels of
      cTnI and Lac were significant decreased at 48 hours after ROSC [cTnI (MUg/L:
      1.83+/-0.68 vs. 2.83+/-0.98, Lac (mmol/L): 5.5+/-1.6 vs. 7.9+/-2.6, both P <
      0.01], the LVEF was slightly higher than that at 72 hours after ROSC (0.690+/
      0.040 vs. 0.650+/-0.041, P = 0.051). Compared with control group, less damage to
      myocardial ultra structure was found in H2 treatment group at 72 hours after
      ROSC. CONCLUSIONS: Inhalation of H2 alleviates cardiac dysfunction and myocardial
      injury after CPR.

PMID- 29017653
TI  - [Effects of HMGB1 inhibition on endoplasmic reticulum stress after myocardial
      ischemia/reperfusion injury in rats].
AB  - OBJECTIVE: To investigate the effect of high mobility group protein B1 (HMGB1)
      inhibition on endoplasmic reticulum stress (ERS) after myocardial
      ischemia/reperfusion (I/R) in rats. METHODS: Forty male Sprague-Dawley (SD) rats
      were randomly divided into four groups (n = 10): sham operation group, I/R model
      group, Gene silencing (HMGB1-siRNA) group, and empty vector (Scrambled-siRNA)
      group. Coronary blood flow of the rats were ligated for 30 minutes, relaxed the
      ligament line for 2 hours, to establish I/R injury model; not ligation with the
      sham operation group. Each group was injected 1 mL phosphate buffer (PBS), HMGB1
      siRNA mixture or Scrambled-siRNA mixture preoperative by tail vein 0 hour, 12
      hours, and 24 hours before surgery. After 2 hours reperfusion, the levels of
      tumor necrosis factor-alpha (TNF-alpha), interleukins (IL-6, IL-8) in the serum
      were detected by enzyme linked immunosorbent assay (ELISA); the expression of
      HMGB1 protein in myocardium was detected by immunohistochemistry; the protein and
      mRNA expressions of HMGB1, GRP78, CHOP and caspase-12 in myocardium were detected
      by Western Blot and real-time fluorescence quantitative reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: Compared with sham operation group,
      the levels of serum inflammatory factor, HMGB1 positive cells, and the protein
      and mRNA expressions of GRP78, CHOP, caspase-12 were significantly increased in
      I/R model group. The levels of serum inflammatory factor in HMGB1-siRNA group
      were significantly lower than those in the I/R model group [TNF-alpha (ng/L):
      783.4+/-203.4 vs. 963.9+/-214.1, IL-6 (ng/L): 358.8+/-94.8 vs. 452.3+/-103.7, IL
      8 (ng/L): 180.5+/-73.6 vs. 347.3+/-90.3, all P < 0.05], HMGB1 positive cells, and
      the protein and mRNA expressions of GRP78, CHOP, caspase-12 in HMGB1-siRNA group
      were significantly lower than I/R model group (HMGB1 protein: 1.59+/-0.26 vs.
      3.21+/-0.40, GRP78 protein: 2.59+/-0.28 vs. 4.21+/-0.42, CHOP protein: 2.01+/
      0.23 vs. 3.21+/-0.43, caspase-12 protein: 1.48+/-0.22 vs. 3.01+/-0.48; HMGB1
      mRNA: 2.35+/-0.26 vs. 4.67+/-0.45, GRP78 mRNA: 6.59+/-0.26 vs. 11.21+/-0.40, CHOP
      mRNA: 2.01+/-0.43 vs. 5.21+/-0.63, caspase-12 mRNA: 4.48+/-0.32 vs. 8.41+/-0.52,
      all P < 0.05). There was no significant difference between the Scrambled-siRNA
      group and the I/R model group. CONCLUSIONS: HMGB1 may be involved in the
      activation of ERS in myocardial I/R injury and increase the damage of myocardial
      cells.

PMID- 29017654
TI  - [Therapeutic effect of hesperidin on severe acute pancreatitis in rats and its
      mechanism].
AB  - OBJECTIVE: To investigate the protective effect of hesperidin on severe acute
      pancreatitis (SAP) in rats and its related mechanism. METHODS: Sixty male Sprague
      Dawley (SD) rats were randomly divided into five groups (n = 12 in each group):
      sham group, SAP model group, dexamethasone group (5 mg/kg), low and high dose of
      hesperidin groups (10 mg/kg and 20 mg/kg). SAP rats were administered a
      retrograde infusion of 3.5% sodium taurocholate solution into the biliopancreatic
      duct after laparotomy. Sham rats were administered with equivalent saline. The
      treatment was intravenously injected 5 minutes after operation through femoral
      vein. After 24 hours, the survival of animals was observed, the level of serum
      amylase, the volume of ascites and the relative specific gravity of the pancreas
      were measured; the pathological changes of pancreatic tissue were observed by
      Hematoxylin-eosin (HE) staining; the levels of serum and pancreatic tissue
      interleukin (IL-1beta, IL-6) and tumor necrosis factor-alpha (TNF-alpha) were
      detected by enzyme linked immunosorbent assay (ELISA); the expression of Toll
      like receptor 4 (TLR4), the phosphorylation of IL-1 receptor associated kinase
      (IRAK1) and nuclear factor-kappaB (NF-kappaB) were detected by Western Blot.
      RESULTS: Compared with SAP model group, the 24-hour survival rate were increased
      in low and high dose of hesperidin groups (83.3%, 100% vs. 58.3%), the volume of
      ascites were reduced (mL: 7.36+/-0.91, 6.10+/-1.02 vs. 13.82+/-2.06), the levels
      of serum amylase were reduced (U/L: 1 081.48+/-78.23, 1 048.58+/-49.97 vs. 1
      990.37+/-127.27), the relative specific gravity of the pancreas were reduced
      [(7.52+/-1.02)%, (5.59+/-0.96)% vs. (11.22+/-0.96)%], and the pathological damage
      of pancreatic tissue were reduced; the levels of serum and pancreatic tissue
      inflammatory factors were reduced in high dose hesperidin group [serum IL-1beta
      (ng/L): 68.08+/-10.49 vs. 130.30+/-23.35, IL-6 (ng/L): 63.88+/-10.47 vs. 158.41+/
      21.38, TNF-alpha (ng/L): 10.42+/-1.49 vs. 18.16+/-2.01; pancreas IL-1beta
      (pg/MUg): 13.87+/-1.84 vs. 20.08+/-1.66, IL-6 (pg/MUg): 21.90+/-3.12 vs. 38.13+/
      3.57, TNF-alpha (pg/MUg): 1.88+/-0.20 vs. 4.26+/-0.58]; the expression of TLR4,
      and the phosphorylation levels of IRAK1 and NF-kappaB were decreased in low and
      high dose of hesperidin groups (the sham operation group was 100, TLR4/beta
      actin: 91.9+/-15.6, 83.7+/-11.2 vs. 168.5+/-9.0, p-IRAK1/IRAK1: 117.4+/-7.6,
      104.7+/-11.5 vs. 173.5+/-15.8, p-NF-kappaB p65/NF-kappaB p65: 119.9+/-9.3,
      105.8+/-12.6 vs. 174.1+/-13.0), with statistically significant differences (all P
      < 0.05). The effects of dexamethasone were similar to that of high dose of
      hesperidin. CONCLUSIONS: Hesperidin could significantly protect SAP rats, and
      this protection was related to the inhibition of TLR4/IRAK1/NF-kappaB signaling
      pathway, and to the reduction of pro-inflammatory cytokine expressions. The
      effect of high dose hesperidin (20 mg/kg) was more significant.

PMID- 29017655
TI  - [Application of active immunization in the prevention of de novo hepatitis B
      virus infection after pediatric liver transplantation with HBcAb positive donor
      liver].
AB  - OBJECTIVE: To investigate the effect of active immunization on prevention of post
      transplantation de novo hepatitis B virus (HBV) infection in patients receiving
      liver grafts from hepatitis B core antibody (HBcAb) positive donors. METHODS: A
      retrospective analysis was conducted. Eighty-seven children undergoing liver
      transplantation from HBcAb positive donors admitted to Tianjin First Center
      Hospital from October 2012 to December 2016 were enrolled, and the data of donors
      and recipients were collected. The hepatitis B vaccine was given before operation
      for hepatitis B surface antibody (HBsAb) > 1 000 U/L; hepatitis B immunoglobulin
      (HBIG) 100 U/kg was given during the operation, in order to prevent children from
      HBV infected by obtaining passive immunity quickly, children with HBsAb < 200 U/L
      after operation were injected with hepatitis B vaccine for booster immunization.
      HBV markers and liver function of recipients were determined before liver
      transplantation and during the follow-up, which up to April 2017. According to
      the children got de novo HBV infection after operation or not, the preventive
      effect of active immunization before and after transplantation operation on HBV
      infection was analyzed and compared. RESULTS: In 87 children who received HBcAb
      positive donor livers, 9 (10.3%) developed de novo HBV infection, which occurred
      in 16 (10, 25) months after liver transplantation. Among the 9 children with HBV
      infection, 7 children had HBsAb < 1 000 U/L before the operation, the ratio was
      statistically increased as compared with the children without HBV infection
      [77.8% (7/9) vs. 37.2% (29/78), P < 0.05]. After the transplantation, 62 children
      of 78 without HBV infection showed a good response to hepatitis B vaccination, 1
      child after inoculation of hepatitis B vaccine, the titer of HBsAb was still less
      than 200 U/L, 15 children without administration of hepatitis B vaccine, only
      with HBIG injection for prevention. The HBsAb of children with de nove HBV
      infection were less than 200 U/L after operation, the ratio was significantly
      increased as compared with children without HBV infection [100.0% (9/9) vs. 20.5%
      (16/78), P < 0.01]. CONCLUSIONS: The establishment of active immunization method
      can effectively prevent children with de novo HBV infection occurred in pediatric
      recipients from HBcAb positive donors with preventive treatment.

PMID- 29017656
TI  - [Development and construction mode of critical care medicine: 22 years of
      development and construction of intensive care units of Guizhou Medical
      University].
AB  - OBJECTIVE: To provide decision-making basis for promoting the rapid and healthy
      development of critical care medicine/intensive care unit (ICU) through
      discussing the mode of development and construction of the department of ICU.
      METHODS: The situations of ICU of Affiliated Hospital of Guizhou Medical
      University from July 1994 to December 2016 were analyzed and summed up. Data of
      the situations in different development stages included the location and area of
      the ward, the number of beds, the number of physicians and nurses, the structure
      of academic titles and educational levels, the number of patients admitted to ICU
      per year, the proportion of patients used ventilator per year, the mortality, the
      mode of the discipline management, the number of medical postgraduates and
      undergraduates trained in the ICU, the number of teaching hours, the
      achievements, the number of research projects, the number of published monographs
      and papers, the number of the multicenter trials that we participated in, the
      construction of the team, the personal honor, and so on. RESULTS: From 1994 to
      2016, the department of ICU had three development stages: the initial development
      stage of the discipline (from July 1994 to March 2005), the standardization
      development stage of the discipline (from April 2005 to December 2015), the
      acceleration development stage of the discipline (from December 2015 to December
      2016). The scale of the department expanded from an open unit with 6 beds which
      was shared with the department of cardiothoracic surgery to 6 enclosed units with
      90 beds which were managed independently by the intensivists. The area of the
      department increased from less than 300 m2 to more than 7 000 m2. There were 46
      beds in the mixed ICU, which covered an area of 4 210 m2. There was only one
      physician in 1994 while the number of the physicians increased to 19 in 2016. The
      number of nurses increased from 4 in 1994 to 69 in 2016. The proportion of highly
      educated talents significantly increased. Furthermore, from 1994 to 2016, the
      number of beds increased from 6 to 46; the number of patients admitted to ICU per
      year increased from 138 to 1 080; and the number of patients used ventilator
      increased from 24 to 1 057. The mean acute physiology and chronic health
      evaluation II (APACHE II) score was > 24.0 at admission, while < 12.6 at
      discharge. From 1997 to 2016, a total of 79 postgraduates had studied in the
      department, and 390 teaching hours we had undertaken. From 2011 to 2016, a total
      of 250 undergraduates had studied in the department, and 540 teaching hours we
      had undertaken. From 1994 to 2016, 8 achievements were obtained, 22 projects were
      undertook, 4 monographs were published, 6 books were edited that the physicians
      in the ICU as key editors, 104 papers were published, and 8 national multicenter
      trials that the physicians in the ICU were as key participants, and multiple team
      and individual honors were obtained. CONCLUSIONS: The construction of ICU
      hardware is the basis and prerequisite for the development of the discipline and
      the construction of ICU software is the soul and motivation of the discipline.
      The operation indexes of clinical medical treatment, teaching and scientific
      researches reflect the overall operation status of the discipline and the
      hospital.

PMID- 29017657
TI  - [Comparative study for effects of bare-handed CPR with Thumper cardiopulmonary
      resuscitator CPR in emergency department based on "the Utstein style"].
AB  - OBJECTIVE: To objectively and standardly compare the bare-handed CPR and Thumper
      cardiopulmonary resuscitation CPR recovery effect based on cardiopulmonary
      resuscitation (CPR) Utstein model. METHODS: A retrospective study was conducted.
      CPR adult patients admitted to the Emergency Room of First Hospital of
      Qinhuangdao in Hebei Province from January 2015 to January 2017 were enrolled.
      Seventy patients who underwent CPR using the Thumper cardiopulmonary resuscitator
      were included in the Thumper CPR group; 80 patients who underwent manual hand
      held CPR were included in the bare-handed CPR group. Return of spontaneous
      circulation (ROSC) and return of spontaneous breathing, and blood gas analysis
      indexes of recovery for 5 minutes and 15 minutes [arterial oxygen partial
      pressure (PaO2), arterial blood carbon dioxide partial pressure (PaCO2), arterial
      blood oxygen saturation (SaO2), blood lactic acid (Lac)] were collected. RESULTS:
      There was no significant difference in gender, age and cardiac arrest (CA) causes
      between the two groups. Compared with the bare-handed CPR group, the ROSC rate in
      the Thumper CPR group was significantly increased [68.57% (48/70) vs. 51.25%
      (41/80), chi2 = 4.642, P = 0.031], but there was no significant difference in
      return of spontaneous breathing rate [48.57% (34/70) vs. 47.50% (38/80), chi2 =
      0.017, P = 0.896]. There was no significant difference in blood gas index between
      the two groups after 5 minutes of recovery. The PaO2 and SaO2 in the Thumper CPR
      group were significantly higher than those in the bare-handed CPR group [PaO2
      (mmHg, 1 mmHg = 0.133 kPa): 88.13+/-5.06 vs. 84.26+/-5.53, SaO2: 0.828+/-0.068
      vs. 0.766+/-0.031, both P < 0.05), PaCO2 and Lac were significantly lower than
      those in the bare-handed CPR group [PaCO2 (mmHg): 34.04+/-4.62 vs. 40.43+/-5.29,
      Lac (mmol/L): 6.90+/-2.07 vs. 8.50+/-2.12, both P < 0.05]. CONCLUSIONS: In the
      process of emergency rescue, Thumper cardiopulmonary resuscitator is more
      successful than bare-handed CPR. The recovery rate of Thumper cardiopulmonary
      resuscitator is more conducive to save manpower and obtain better metabolic
      effect, which is worthy of clinical promotion and application.

PMID- 29017658
TI  - [Effect of a stabilization device for maintaining the balance of a CPR performer
      during ambulance transportation on quality of CPR in out-of-hospital cardiac
      arrest: a prospective randomized controlled trial].
AB  - OBJECTIVE: To investigate the effect of a stabilization device for maintaining
      the balance of a cardiopulmonary resuscitation (CPR) performer during ambulance
      transportation on quality of CPR in out-of-hospital cardiac arrest (OHCA).
      METHODS: A prospective randomized controlled trial was performed. 167 OHCA
      patients with cardiac arrest (CA) time < 10 minutes admitted to Cangzhou Central
      Hospital from October 2014 to January 2017 were enrolled, and divided into armed
      stabilization device group (n = 86) and unarmed stabilization device group (n =
      81) by random number table. Restoration of spontaneous circulation (ROSC) rate,
      24-hour survival rate and survival rate of discharge were evaluated. RESULTS:
      Compared with unarmed stabilization device group, ROSC rate (29.1% vs. 9.9%, chi2
      = 9.691, P = 0.002), 24-hour survival rate (20.9% vs. 6.2%, chi2 = 7.649, P =
      0.006) and survival rate of discharge (12.8% vs. 3.7%, chi2 = 4.485, P = 0.035)
      were significant increased in armed stabilization device group. CONCLUSIONS: CPR
      with stabilization device during ambulance transport could effectively ensure
      quality of CPR and improve prognosis in OHCA. Clinical Trial Registration:
      Chinese Clinical Trial Registry, ChiCTR-IPR-14005337.

PMID- 29017659
TI  - [Massive pulmonary embolism similar to acute myocardial infarction rescued by
      ECMO: a case report].
AB  - Acute myocardial infarction (AMI) and acute massive pulmonary embolism can be
      characterized by no pulse electrical activity. Patients of cardiac arrest (CA)
      with no pulse electrical activity have a high mortality rate before the cause was
      corrected. Extracorporeal membrane oxygenation (ECMO), as a kind of artificial
      heart-lung support organ, provides treatment for CA patients. A case of massive
      pulmonary embolism similar to AMI was treated in the Third Central Hospital of
      Tianjin, who received interventional thrombolysis assisted by ECMO. Through the
      review of the overall development of the case, we aim to broaden the diagnosis
      and treatment of CA patients with no pulse electrical activity, and to improve
      the understanding of the complications secondary to ECMO.

PMID- 29017660
TI  - [Rhythm analysis in CPR].
AB  - It's necessary to interrupt cardiopulmonary resuscitation (CPR) for a reliable
      automatic external defibrillator (AED) rhythm analysis, because the mechanical
      activity from the chest compressions introduces artifacts in the
      electrocardiogram (ECG) that substantially lower the capacity of an AED to judge
      cardio-electric rhythm. However, repeated interruptions of compression will
      reduce the quality of CPR, which in turn affect the prognosis of patients with
      cardiac arrest (CA). In order to improve the quality of CPR, reduce the
      interruptions of chest compression and implement accurate defibrillation, people
      have made many efforts on identifying ECG rhythm in CPR. The studies can be
      grouped into two broad categories: those based on the artificial mixture of ECG
      data and CPR artifacts and those based on CA data recorded during CPR. This
      article introduced researches for rhythm recognition in CPR, including sources
      and characteristics of CPR artifacts, methods of rhythm analysis, and provided a
      basis for the study of how to improve the accuracy of cardio-electric rhythm
      recognition.

PMID- 29017661
TI  - [Advances in the role of autophagy in acute pancreatitis].
AB  - Autophagy is a self-protect cellular mechanism by which the unneeded cellular
      structure or impaired protein are targeted to degeneration. Acute pancreatitis
      (AP) is associated with autophagy tightly. This article is aimed to mainly
      elaborate the phenomenon that AP can be triggered by impaired autophagy and the
      mechanism of AP exacerbation by damaged autophagy. In AP, the reasons of impaired
      autophagy is dysfunction of cathepsins and lysosome associated membrane protein,
      which present as vacuoles accumulation in acinar cells and combination disorder
      of autophagolysosome, finally to activation of trypsin. By the relocation of high
      mobility group box 1 (HMGB1) and promotion of mitochondrial permeability
      transition (MPT), impaired autophagy aggravates AP. Understanding the above
      mechanism has certain significance to the prevention and treatment of AP.

PMID- 29017662
TI  - [Progresses of immunomodulatory therapy in sever acute pancreatitis].
AB  - Severe acute pancreatitis (SAP) is accompanied with complex pathogenic course and
      high mortality. The imbalance of immune response is an important cause which
      leads the SAP patients to the severe situation and even death. The
      immunomodulatory therapy can regulate the imbalance of inflammation, alleviate
      SAP-associated organ injury, and improve the prognosis of patients. Previous
      immunomodulatory therapy had some problems, such as single-object and simple
      method. In recent years, some new methods of immunomodulatory therapy, such as
      regulating the apoptosis and mature of immune cells, applying of mesenchymal stem
      cells (MSCs) and multi-regulation methods, provide some new ideas and hopes for
      SAP therapy. This paper reviewed the history and recent research progresses of
      SAP immunomodulatory therapy.

PMID- 29017663
TI  - [Research progress of frailty syndrome in critically ill elderly patients].
AB  - Frailty syndrome is the core of the comprehensive geriatric assessment of the
      elderly, which affects the prognosis of elderly critical illness patients and
      becomes the hotspot of the current geriatric medical research of elderly
      patients. In critically ill elderly patients, the incidence rate of frailty
      syndrome is 21%-59%. Frailty syndrome is an independent risk factor in elderly
      patients with complications, short-term and long-term mortality. Moreover frailty
      is always accompanied by poor state and affects the health quality of these
      patients. In the field of critical care medicine in our country, the study of the
      frailty syndrome is still in its infancy. This article focuses on the research
      progress of frailty syndrome, and the assessment of the frailty critical illness
      elderly patients is helpful for the clinical doctors to determine the prognosis
      and treatment decision.

PMID- 29017664
TI  - Diabetes and Coronary Artery Disease: Role of Functional Imaging.

PMID- 29017665
TI  - Folic Acid Effect on Artemether-Induced Cardiac Anomalies in Mice Embryos.
AB  - OBJECTIVE: To determine the role of folic acid in preventing the adverse effects
      of artemether, on fetal heart in Albino mice. STUDY DESIGN: Experimental study.
      PLACE AND DURATION OF STUDY: Department of Anatomy, University of Health
      Sciences, Lahore, from July 2011 to January 2012. METHODOLOGY: Eighteen pregnant
      Albino mice were randomly divided into three groups A, B, and C of six mice each.
      The control group Awas treated with intramuscular injection of solvent arachis
      oil 10.7 mg/kg, group B was given intramuscular injection of artemether 10.7
      mg/kg, and group C was given intramuscular injection of artemether 10.7 mg/kg and
      folic acid 4.93 mg/kg, dissolved in 0.1 ml. of distilled water orally, from 6th
      to 10th day of pregnancy. On 18th gestational day, the mice were sacrificed, and
      dissected to deliver live fetuses of group A(n=46), group B (n=16), and group C
      (n=20) were delivered. After dissection of the fetuses, the hearts were isolated
      and fixed in 10% formalin and processed in a usual way for histological
      examination with the light microscope after H&E staining, using X4, X10, and X40
      objectives. The sections were evaluated for presence of septal defects, thickness
      of ventricular and atrial septa was calculated by micrometery. For statistical
      analysis, SPSS version 18 was used. RESULTS: Post-Hoc Tukey's test indicated
      statistically significant difference in mean atrial septal thickness between
      groups Aand B (p < 0.001), groups B and C (p=0.015), and insignificant difference
      between groups Aand C (p=0.178). There was statistically significant thinning of
      ventricular septa between groups Aand B (p < 0.001), groups B and C (p < 0.001),
      and groups Aand C (p < 0.001). CONCLUSION: Folic acid protected the toxic effects
      of artemether on the development of heart.

PMID- 29017666
TI  - Protective Effects of Nigella Sativaon Acetylsalicylic Acid-Induced
      Nephrotoxicity in Albino Rats.
AB  - OBJECTIVE: To see the effects of Nigella sativaon acetylsalicylic acid-induced
      nephrotoxicity in albino rats. STUDY DESIGN: An experimental study. PLACE AND
      DURATION OF STUDY: The Anatomy Department of University of Health Sciences,
      Lahore, from January 2014 to December 2015. METHODOLOGY: Thirty-two female albino
      rats were divided into four groups. Group A(control) was given single dose of 10
      mg/100 gm body weight of 1% methylcellulose, orally. Group B and C were treated
      with oral 1000 mg/kg acetylsalicylic acid as a single dose. Group D was given 250
      mg/kg ethanolic extract of Nigella sativa(NSE) by oral gavage followed by single
      dose of 1000 mg/kg acetylsalicylic acid on 1st day of experiment; after that only
      NSE was continued till 7 days. Animals of groups A, C and D were sacrificed on
      day 8 and that of group B on day 2 of experiment. Cardiac puncture was performed
      to draw blood from each animal for renal function tests. Animals were evaluated
      for gross (Paired kidney weight, body weight, relative tissue body weight index)
      as well as for biochemical (Serum urea and creatinine) parameters. RESULTS: Gross
      as well as biochemical parameters were markedly impaired in group B, but
      statistically significant improvement was noticed in Nigella sativatreated group.
      There was no self recovery in group C. CONCLUSION: Ethanolic extract of Nigella
      sativahas a protective role against acetylsalicylic acid-induced nephrotoxicity
      in albino rats.

PMID- 29017667
TI  - Supervisors' Perspective on Electronic Logbook System for Postgraduate Medical
      Residents of CPSP.
AB  - OBJECTIVE: To find out the perspective of the supervisors about the role of
      electronic logbook (E-Logbook) of College of Physicians and Surgeons, Pakistan
      (CPSP) in monitoring the training of postgraduate medical residents of CPSP.
      STUDY DESIGN: Descriptive cross-sectional study. PLACE AND DURATION OF STUDY:
      College of Physicians and Surgeons Pakistan (CPSP), Karachi, from May to October
      2015. METHODOLOGY: An electronic computer-based questionnaire designed in
      Hypertext Preprocessor (PHP) language was distributed to the registered
      CPSPsupervisors through the e-log system. The questionnaire comprised of seven
      close ended questions. The data were entered and analyzed by SPSS version 20.
      Descriptive statistics were determined. RESULTS: Atotal of 1,825 supervisors
      responded to the questionnaire. Fifteen hundred and ninety-eight (87.6%)
      supervisors gave regular feedback for their trainees, 88.2% considered it a
      better monitoring tool than conventional logbook, 92.5% responded that e-logbook
      helped in the regular assessment of the trainees, 87.8% believe that quality of
      training will improve after introduction of e-logbook, 89.2% found e-logbook
      useful in implementation of outcome-based learning and 88.4% considered e-logbook
      user-friendly. The main reasons for not providing regular feedback included the
      supervisors not familiar to e-logbook interface, internet access problems, and
      busy schedules of supervisors. CONCLUSION: There was a wide acceptability of the
      e-log system among the supervisors with positive perception about its usefulness.
      The common reasons that hinder the provision of regular feedback include not
      being familiar to e-log interface, internet access problem, busy schedule and
      some consider using e-logbook a cumbersome task. These reasons can be alleviated
      to provide a better training monitoring system for the residents.

PMID- 29017668
TI  - Frequency of Her2/Neu Protein Expression in Ovarian Epithelial Cancers.
AB  - OBJECTIVE: To detect the frequency of Her-2/neu protein expression in epithelial
      ovarian cancers by immunohistochemistry. STUDY DESIGN: Descriptive cross
      sectional study. PLACE AND DURATION OF STUDY: Department of Pathology, King
      Edward Medical University, Lahore, from July 2014 to May 2015. METHODOLOGY: Fifty
      six cases diagnosed as epithelial ovarian cancer on histopathology were included
      in this study. Immunohistochemistry was performed to observe the pattern of
      HER2/neu protein expression in these cases. Association with age was determined
      by Chi-square test with significance at p<0.05. RESULTS: Out of these 56 cases,
      38 (67.9%) were serous cystadenocarcinomas, 11 (19.6%) were endometrioid
      adenocarcinomas, 6 (10.7%) were mucinous cystadenocarcinomas and 1 (1.8%) was non
      Brenner transitional cell carcinoma. The mean age of patients was 49.61 +/-13.20
      years with minimum and maximum ages of 21 years and 80 years, correspondingly.
      Twentyone (37.5%) out of 56 patients were found to overexpress Her-2/neu protein.
      CONCLUSION: Her-2/neu protein overexpression was observed in 21 (37.5%) patients.
      No statistically significant association was seen between age and Her-2/neu
      protein overexpression.

PMID- 29017669
TI  - Relationship of the Van Herick Grading System with Peripheral Iris Configuration
      and Level of Iris Insertion.
AB  - OBJECTIVE: To determine the relationship of the van Herick angle grading system
      with the level of iris insertion and peripheral iris configuration. STUDY DESIGN:
      Observational study. PLACE AND DURATION OF STUDY: Eye department, Combined
      Military Hospital, Malir Cantt., Karachi, from May to October 2015. METHODOLOGY:
      Sixty-five eyes of 65 patients were recruited. Anterior chamber depth at the
      temporal limbus was measured as a fraction of corneal section thickness using van
      Herick technique and graded on the standard 4-point scale of the van Herick
      grading system. Gonioscopy of the temporal quadrant was performed with a Posner 4
      mirror goniolens and both the true level of iris insertion and peripheral iris
      configuration were recorded on a 4-point scale so as to equate with the van
      Herick 4-point grading system. Spearman's rho test was applied to determine the
      relationship of the van Herick grading system with level of iris root insertion
      and peripheral iris configuration. RESULTS: Amoderate positive correlation
      between van Herick grade and peripheral iris configuration was found which was
      statistically significant (rs=0.42, p < 0.001). Astatistically significant and
      moderate positive correlation was also detected between van Herick grade and the
      level of iris insertion (rs=0.45, p < 0.001). CONCLUSION: The van Herick grade
      has a moderately positive relationship with the peripheral iris configuration and
      true level of iris insertion.

PMID- 29017670
TI  - Visual and Topographical Outcomes Following Accelerated Trans-Epithelial Corneal
      Crosslinking in Progressive Keratoconus.
AB  - OBJECTIVE: To assess the visual and topographical outcomes following accelerated
      trans-epithelial corneal crosslinking (TE-CXL) in progressive keratoconus. STUDY
      DESIGN: Case series. PLACE AND DURATION OF STUDY: Laser Vision Centre, Karachi,
      from January 2015 to December 2016. METHODOLOGY: Forty-five eyes of 25 patients
      affected with progressive keratoconus and treated with accelerated TE-CXL with
      riboflavin (vitamin B2) and ultra-violet A(UV-A) irradiation were enrolled in
      this study. The visual outcome was measured by ETDRS chart as improvement in best
      corrected visual acuity (BCVA) of at least one line or more as compared to pre
      CXLBCVA. The topographical outcome was measured as decrease in maximum simulated
      keratometry values, astigmatism and spherical equivalent (SE) and an increase in
      central corneal thickness (CCT). K-max was defined as the steepest radius of
      curvature of the anterior corneal surface. SE was measured by subjective
      refraction, and K-max, astigmatism and CCTby scanning-slit corneal topography.
      Patients were followed-up 12 months post-treatment. RESULTS: At the end of follow
      ups, mean BCVAshowed improvement of one line from LogMAR 0.58 +/-0.067 to LogMAR
      0.48 +/-0.077. Seven (15.5%) eyes showed two lines of improvement while 3 (6.7%)
      eyes showed worsening of one line in BCVA. The mean K-max flattened by 0.7D. Mean
      astigmatism and SE decreased up to -0.5D and -0.4D, respectively. Mean
      preoperative CCTwas 454.31 +/-36.34 um, whereas mean postoperative CCTwas 456.47
      +/-35.60 um with an average increase of 2.15 um. No postoperative complications
      were reported. CONCLUSION: Based on topographical outcomes, accelerated TE-CXL is
      effective in preventing the progression of keratoconus without any safety
      concerns with improvement of vision in majority of cases.

PMID- 29017671
TI  - Could Red Cell Distribution Width be a Marker of Thyroid Cancer?
AB  - OBJECTIVE: To study red cell distribution width (RDW) values, a novel
      inflammatory marker in routine hemogram, of patients with benign or malignant
      thyroid nodules and to compare with healthy population. STUDY DESIGN: Descriptive
      study. PLACE AND DURATION OF STUDY: Abant Izzet Baysal University Hospital, Bolu,
      Turkey, from November 2015 and February 2017. METHODOLOGY: The hemogram values of
      patients undergone thyroid surgery for thyroid nodule between November 2015 and
      February 2017 were retrospectively analyzed, and compared to those in healthy
      subjects. Subjects with infectious or inflammatory diseases were excluded.
      Patients' characteristics and laboratory data were obtained from institutional
      computerized database. Preoperative hemogram values of thyroid nodule patients
      were recorded. One-way ANOVAand Kruskal-Wallis tests were performed to compare
      variables with significance at p<0.05. RESULTS: Median RDW of malignant nodule
      group was 15.8 (12.9-19.5) and was significantly higher than both of those in
      benign nodule (15) and control groups (14), (p<0.001). CONCLUSION: Elevated RDW
      in patients with thyroid nodules in preoperative period should alert the
      physician for possible malignancy and this cost-effective marker also can help
      support other modalities (ultrasound scan, and fine needle aspiration biopsy) to
      distinguish malignant from benign nodules.

PMID- 29017672
TI  - Surgical Outcome of Pancreaticoduodenectomy in Pancreatic and Periampullary
      Neoplasms.
AB  - OBJECTIVE: To report the results in the surgical treatment of pancreatic and
      periampullary neoplasms with emphasis on surgical technique, short-term
      postoperative outcome and the lessons learnt. STUDY DESIGN: Case series. PLACE
      AND DURATION OF STUDY: This study was carried out at Shaukat Khanum Memorial
      Cancer Hospital and Research Center, Lahore, from October 2014 to May 2016.
      METHODOLOGY: Patients undergoing surgical treatment of pancreatic and
      periampullary neoplasms were selected. Patients' characteristics including
      demographics, surgical technique, and 30-day morbidity and mortality were
      recorded. International Study Group of Pancreatic Fistula (ISGPF) classification
      was used to define postoperative pancreatic fistula and Clavien-Dindo
      classification to grade complications. RESULTS: Atotal number of 65 patients
      underwent the trial of dissection; 50 had pancreaticoduodenectomy and 15 patients
      underwent palliative bypass and were excluded from analysis. Sixty-four percent
      were males and 36% were females. The most common tumor was periampullary (n=29,
      58%) followed by pancreatic head (14, 28%) and duodenal tumors (n=07, 14%). Mean
      age was 52.92 +/-13.27 years; mean operating time was 470 +/-358.28 minutes and
      median blood loss was 400 (287-500) ml. Pancreaticogastrostomy (PG) was the
      preferred reconstruction technique in 37 (74%) verses pancreaticojejunostomy (PJ)
      in 13 (26%) patients. Four (08%) patients needed portal vein reconstruction and
      two (04%) replaced right hepatic artery resection and reconstruction due to tumor
      involvement. There were seven Grade A, and one Grade B and C pancreatic fistulae
      each. Three patients (06%) needed endoscopic therapy for gastrointestinal
      hemorrhage from pancreatic stump. There was one death in postoperative period.
      CONCLUSION: Pancreaticoduodenectomy is a safe procedure with excellent
      postoperative outcome, if carried out in a specialized hepato-pancreato-biliary
      unit. APG reconstruction can be a safer alternative to PJ.

PMID- 29017673
TI  - Iatrogenic Gastrointestinal Perforation Following Therapeutic Endoscopic
      Procedures: Management and Outcome.
AB  - The aim of this study was to analyze the location, the cause and treatment of
      iatrogenic gastrointestinal perforations following therapeutic endoscopic
      procedures. Perforation occurred in 12 patients out of 3,389, giving cases
      occurred intraoperatively or postoperatively. Among them, 6 cases were closed by
      titanium clipping and 1 case by purse string suture. In another case after cap
      assisted endoscopic mucosal resection (EMRC), attempted titanium clipping failed,
      emergency surgery had to be performed. One each case, after Argon plasma
      coagulation (APC) and case after endoscopic piecemeal mucosal resection (EPMR),
      recovered well spontaneously. In two cases, titanium clips fell off endoscopic
      mucosal resection (EMR) resulting in delayed perforation, required surgery. Key
      factors for preventing and managing the perforation of endoscopic treatment,
      include the choice of endoscopic approach, processing method of perforation,
      detail processing in endoscopic therapy, proficient degree of operators and
      psychological quality.

PMID- 29017674
TI  - Calcium Regulation in Alzheimer's Disease: Mechanistic Understanding.
AB  - This study is systematic review of the research, focused on all possible pathways
      involved in calcium (Ca2+) regulation in order to utilize them in the control and
      remediation of Alzheimer's disease (AD), because Ca2+ plays important role in
      pathogenesis of AD. Electronic databases, Science Direct and PubMed/Medline, for
      relevant publications between 2000April 2017, were searched. Ca2+ ions are very
      important in cell signaling in body, specially the neuronal signaling. Many
      pathways are involved in normal neuronal Ca2+ signaling. AD is one of the most
      commonly known neurodegenerative disorders, causing dementia and some other
      neuropathological signs in mostly elderly people reaching a rate of 44 million
      until now. Depending upon certain possibilities, many hypothesis were proposed
      related to AD; out of which, one is Ca2+ hypothesis. According to this
      hypothesis, disturbance in Ca2+ signaling pathway due to certain reasons, such as
      accumulation of beta-amyloid proteins, ER stress, cytochrome c activation etc.,
      causes AD. Due to less clinical research, only few FDAapproved pharmaceuticals
      are available for treatment of AD. Reviewed studies suggest that Ca2+ channel
      blocker and initiator may play an important role in cure of AD.

PMID- 29017675
TI  - Familial Hodgkin Lymphoma.
AB  - Hodgkin Lymphoma (HL) is a lymphoid tumour that represents about 1% of all
      neoplasms occurring worldwide. HLis the most treatable of childhood malignancies.
      The etiology of HLis unknown. However, increase risk has been reported in males,
      with autoimmune diseases, poor socioeconomic status, increased family size,
      Ebstein Barr Virus (EBV) exposure, congenital or acquired immunodeficiency and
      those with a family history of HL. Familial HLis rare. The risk of developing
      HLis increased six times in the siblings of the affected patients. Both genetic
      and environmental factors have been postulated in the pathogenesis. No case of
      familial HLhas been reported in the literature from Pakistan. We report two
      families with familial HLoccurring in siblings that have been successfully
      treated and are on our follow-up.

PMID- 29017676
TI  - Rare Cause of Pleuropnemonia: Tularemia Disease.
AB  - Tularemia is a zoonotic infection which is caused by gram negative coccobacilli,
      Francisella tularensis. The disease occurs after contact with blood and body
      fluids of infected animals, bites and ingestion of infected food and water.
      Although it commonly presents with skin lesions, there may also be serious organ
      involvements. A55-year woman was consulted for presumptive diagnosis of
      tuberculosis. Multiple lymphadenopathy in right cervical area was present on
      physical examination. Pleural effusion on left side was detected with computed
      tomography. In detailed history, knowledge of a family member with the diagnosis
      of tularemia was obtained. Both of them had the history of contact with infected
      animals. Diagnosis of tularemia was confirmed with microagglutination test. With
      this patient who was initially presumptively diagnosed as tuberculosis, we aim to
      draw attention to diagnosis of tularemia in the presence of pleuropnemonia and
      peripheral lymphadenopathy and emphasize importance of detailed patient history.

PMID- 29017677
TI  - Artery of Percheron Infarct: ARarity Not to be Missed.
AB  - Artery of Percheron (AOP) is a rare vascular variant of posterior cerebral
      circulation and it supplies blood to the bilateral paramedian thalami and the
      rostral midbrain. Artery of Percheron infarct requires a comprehensive clinical
      and radiological examination. It can be easily overlooked due to normal
      CTfindings and wide range of differential diagnosis. Classic triad of
      presentation is altered mental status, memory impairment and the vertical gaze
      palsy. We report a case of a 66-year female who had sudden onset of severe
      vertigo, diplopia and ataxia. Anon-contrast CTBrain was performed which was
      normal. Her MRI brain with diffusion weighted images (DWI) confirmed bilateral
      thalamic infarcts which were initially thought to be calcifications, as usually
      happens with diagnosing artery of Percheron infarcts. However, by reviewing and
      ruling out all other possible causes of such symptoms and further review of
      neuroimaging, lead us to the correct diagnosis.

PMID- 29017678
TI  - Mammary Analogue Secretory Carcinoma of Parotid Gland in a Teenage Boy.
AB  - Mammary analogue secretory carcinoma (MASC) is a rare salivary gland malignancy
      that exhibits resemblance with secretory carcinoma of the breast (SC) due to the
      presence of ETV6-NTRK3 gene fusion, formerly classified as acinic cell carcinoma.
      It is a slowly growing painless tumor that exhibits wide range of clinical
      behavior. This tumor typically affects middle aged people. Less than 100 such
      cases have been reported in the literature so far with only 8 case reports of
      patients less than 19 years of age. Very little is known about the clinical
      management of such cases. We hereby report a case of 15-year boy who had been
      managed for MASC of left parotid gland with exision.

PMID- 29017679
TI  - Pulmonary Papillary Adenoma: Report of Two Cases.
AB  - Pulmonary papillary adenoma is a rare tumor. Two cases without any clinical
      symptoms were enrolled in our hospital. Both cases were incidentally detected in
      pulmonary area by imaging. Pathological examination revealed well-circumscribed
      nodules consisting of papillary growth of cuboidal to low columnar epithelial
      cells lining the surface of the fibrovascular stroma. Immunohistochemistry (IHC)
      staining showed that the lining cells were diffusely positive for TTF-1, CK, p63,
      CK7, and Napsin A. The Ki-67 proliferation index was approximately 2%. The
      morphological features and the IHC profile of the tumor were in agreement with
      that of pulmonary papillary adenoma. Both patients are doing well without
      recurrence or metastasis of the tumor.

PMID- 29017680
TI  - Carotid Intima Media Thickness Percentiles for Pakistani Population.
AB  - Carotid artery intima media thickness estimation is a well-established way of
      cardio vascular disease evaluation. The purpose of this cross-sectional study was
      to develop normal carotid intima media thickness percentile values for a
      Pakistani cohort. Data was collected at the Departments of Radiology and Family
      Medicine, The Aga Khan University Hospital, Karachi, from April 2014 to August
      2015. High frequency ultrasound of carotid was done in 257 patients [97 male
      (38%), 160 female (62%)] without any known carotid artery disease. Reference
      ranges (90% range between 5th and 95th centiles) were constructed for each common
      carotid and internal carotid artery measurement and displayed in graph form. The
      mean difference was found in left common carotid artery (0.55 +/-0.13) and left
      internal carotid artery thickness (0.50 +/-0.10) significant at p=0.031 and
      p=0.014, respectively. The IMTpercentile graphs developed in this study for
      internal and common carotid arteries are exclusive for this population and can be
      used to assess vascular health from ultrasound measurements.

PMID- 29017681
TI  - pH of Bottled Drinking Water in Islamabad.

PMID- 29017682
TI  - Calcifying Cystic Odontogenic Tumor.

PMID- 29017683
TI  - The Appropriate Sample to Define Functional Dyspepsia.

PMID- 29017684
TI  - Mechanical Intestinal Obstruction Caused by Migration of Deflated Intragastric
      Balloon.

PMID- 29017685
TI  - Communication Education for Trainees through Role Play and Dynamic Self
      Assessment.

PMID- 29017686
TI  - Trend of Antibiotic Sensitivity of Escherichia Coli in Patients with Urinary
      Tract Infection.

PMID- 29017687
TI  - Expression of vascular endothelial growth factor A isoforms is dysregulated in
      women with endometriosis.
AB  - Angiogenesis is a critical step in the development of ectopic lesions during
      endometriosis. Although total vascular endothelial growth factor (VEGF) A is
      elevated in the peritoneal fluid of women with endometriosis, there are
      contradictory reports on how levels of total endometrial VEGFA are altered in
      this disease. Furthermore, limited research is available on different VEGFA
      isoforms in women with endometriosis. Thus, the aim of the present study was to
      analyse levels of various VEGFA isoforms in women with and without endometriosis
      at different stages of the menstrual cycle. Quantitative polymerase chain
      reaction analysis showed that total VEGFA was highest during menstruation in
      endometriosis compared with controls (P=0.0373). VEGF121 and VEGF189 were
      similarly highest during menstruation in endometriosis compared with controls
      (P=0.0165 and 0.0154 respectively). The present study is also the first to
      identify the natural expression of VEGF111 in human tissue, which is also highest
      during menstruation in endometriosis (P=0.0464). This discovery of the natural
      production of VEGF111 in human endometrium, as well as the upregulation of VEGFA
      isoforms during menstruation in endometriosis, may shed further light on the
      development and progression of the disease, and improve our understanding of the
      regulation of endometrial angiogenesis.

PMID- 29017689
TI  - Peristomal Lesions in Crohn's Disease: Are They Always Fistulae?

PMID- 29017688
TI  - Cannabinoids in Pain Management and Palliative Medicine.
AB  - BACKGROUND: There are conflicting interpretations of the evidence regarding the
      efficacy, tolerability, and safety of cannabinoids in pain management and
      palliative medicine. METHODS: We conducted a systematic review (SR) of systematic
      reviews of randomized controlled trials (RCT) and prospective long-term
      observational studies of the use of cannabinoids in pain management and
      palliative medicine. Pertinent publications from January 2009 to January 2017
      were retrieved by a selective search in the Cochrane Database of Systematic
      Reviews, the Database of Abstracts of Reviews of Effects, and Medline. The
      methodological quality of the SRs was assessed with the AMSTAR instrument, and
      the clinical relevance of quantitative data syntheses was assessed according to
      the standards of the Cochrane Collaboration. RESULTS: Of the 750 publications
      identified, 11 SRs met the inclusion criteria; 3 of them were of high and 8 of
      moderate methodological quality. 2 prospective long-term observational studies
      with medical cannabis and 1 with tetrahydrocannabinol/cannabidiol spray (THC/CBD
      spray) were also analyzed. There is limited evidence for a benefit of THC/CBD
      spray in the treatment of neuropathic pain. There is inadequate evidence for any
      benefit of cannabinoids (dronabinol, nabilone, medical cannabis, or THC/CBD
      spray) to treat cancer pain, pain of rheumatic or gastrointestinal origin, or
      anorexia in cancer or AIDS. Treatment with cannabis-based medicines is associated
      with central nervous and psychiatric side effects. CONCLUSION: The public
      perception of the efficacy, tolerability, and safety of cannabis-based medicines
      in pain management and palliative medicine conflicts with the findings of
      systematic reviews and prospective observational studies conducted according to
      the standards of evidence-based medicine.

PMID- 29017691
TI  - Addenda.

PMID- 29017690
TI  - The Range and Scientific Value of Randomized Trials.
AB  - BACKGROUND: The randomized, controlled trial (RCT) is the gold standard of
      scientific evidence for the attribution of clinical effects (benefits and harms)
      to medical interventions. Many different designs for RCTs have been developed in
      order to counter legitimate critical objections and to better adapt the trials to
      the continually changing challenges that face clinical research. METHODS: The
      diversity and adaptability of randomized trial designs are presented and
      discussed on the basis of a selective literature review and specific illustrative
      examples. RESULTS: A wide range of RCT designs enables adaptation to special
      research tasks and clinical framework conditions. These include (among others)
      crossover trials, n=1 trials, factorial RCT designs, and cluster-randomized
      trials. In addition, adaptive designs such as modern platform trials and
      pragmatic RCTs with simplified clinical questions and less severely restricted
      patient groups make broad recruitment of patients possible even in routine
      clinical practice. CONCLUSION: Only the randomized allocation of subjects to the
      treatment and control groups, which is the defining property of RCTs, can
      adequately ensure that traits of the subjects which might disturb or bias a
      comparison of two or more medical interventions, will be evenly distributed
      across groups, regardless of whether these traits are known or unknown. The
      methodological variants and further elaborations of the RCT that are discussed
      here will help protect patients by enabling the assessment of the benefits and
      harms of medical methods and products on the basis of robust evidence even in the
      present era of rapid innovation.

PMID- 29017692
TI  - Misuse of Cortisone Eyedrops.

PMID- 29017693
TI  - Useful Pointers.

PMID- 29017694
TI  - In Reply.

PMID- 29017695
TI  - Ocular Signs Should Be Given Attention.

PMID- 29017696
TI  - Falls Are More Common Than Traffic Crashes.

PMID- 29017697
TI  - Tissue Pressure and Perfusion.

PMID- 29017698
TI  - In Reply.

PMID- 29017699
TI  - Urinary calcium excretion and bone turnover in osteoporotic patients?.
AB  - INTRODUCTION: It is well documented that patients with osteoporosis (OP) have
      high incidence of hypercalciuria (HC). However, the mechanism of HC in patients
      with OP is not well established. It is thought to be the result of high bone
      turnover (HBT) with excessive bone resorption. OP also frequently presents with
      low bone turnover (LBT). At this time, it is not clear whether OP with LBT is
      also associated with hypercalciuria. PURPOSE: The purpose of this study is to
      evaluate urinary calcium excretion in osteoporotic patients with HBT and LBT.
      MATERIALS AND METHODS: This is a retrospective study of 132 patients with
      osteoporosis who underwent bone biopsy at the University of Kentucky between
      January 2010 and December 2012. Based on bone biopsy results, patients were
      divided into HBT or LBT groups. Demographic data, medical history, bone mineral
      density, serum creatinine, calcium, phosphorus, estimated glomerular filtration
      rate (eGFR), filtered calcium load, fractional excretion of calcium and
      phosphorus, 25-hydroxy vitamin D levels, and 24-hour urinary calcium excretion
      and creatinine were obtained from the patients' medical records. Also, intact
      parathyroid hormone (iPTH), serum osteocalcin, bone-specific alkaline
      phosphatase, N-telopeptide of type I collagen, and urine pyridinium levels were
      measured. RESULTS: Hypercalciuria was present in approximately half of the
      patients in both the HBT and LBT groups. Patients with HBT OP were significantly
      younger than those with LBT OP (p = 0.013). There was no difference between HBT
      and LBT patients in 24-hour urinary calcium excretion, serum creatinine, calcium,
      phosphorus, eGFR, filtered calcium load, and fractional excretion of phosphorus.
      Mean values of serum osteocalcin and serum N-telopeptide of type I collagen were
      significantly lower in the LBT compared to the HBT group (p = 0.000 and 0.0152,
      respectively). There was a significant correlation between filtered calcium load
      and urinary calcium excretion in HBT patients but not in patients with LBT.
      Fractional excretion of calcium significantly correlated with urinary calcium
      excretion in both groups. There was no correlation between kidney function and 24
      hour urinary calcium excretion. There was no correlation between dual-emission X
      ray absorptiometry T-scores and 24-hour urinary calcium excretion. CONCLUSION: HC
      is frequently present in patients with OP regardless of the underlying bone
      turnover status. This may suggest the presence of a bone-derived renal calcium
      regulating factor(s). Further studies are needed to understand the exact
      mechanism and the potential consequences of HC in OP patients.?.

PMID- 29017700
TI  - Switching temporary hemodialysis catheters to long-term catheters: exchange
      versus de-novo placement, any difference in line infection??.
AB  - BACKGROUND: Shifting from a short-term catheter to a long-term one is done either
      by removing the old catheter and placing a new long-term one via fresh new
      puncture site, or by replacing the old catheter with a long-term one over a
      guidewire. AIM: We aimed to describe our technique in changing a temporary line
      to a long-term catheter (LTC) over a guidewire and to determine the incidence of
      line-related infections following this procedure. MATERIALS AND METHODS: A
      retrospective pilot study was conducted between 2005 and 2010 at the American
      University of Beirut Hospital. We compared the first group (A), which consisted
      of 20 patients who underwent exchange of a short-term dialysis catheter with a
      tunneled one over a guidewire using our technique, to a second group (B) of 60
      patients who underwent de-novo LTC placement. The two groups were matched by age,
      with a follow-up of at least 1 month. RESULTS: The technical success rate of the
      catheter-conversion procedure was 100%. Our results revealed no significant
      difference of catheter duration between the two groups, with median duration of
      6.5 vs. 4.0 days for group A and group B, respectively (p = 0.21). Moreover,
      there was also no significant mean time difference between any infection and long
      term catheter (LTC) insertion among the two groups (p = 0.31). Furthermore, there
      was no difference of catheter infection between the two groups (p = 0.1).
      CONCLUSION: We concluded that there was no difference in terms of side effects or
      risk of infection in the guidewire group when compared to standard technique.?.

PMID- 29017701
TI  - Comment to: Differences in characteristics and outcomes between community- and
      hospital-acquired acute kidney injury: A systematic review and meta-analysis.
      Clinical Nephrology, 2017; 88: 167-182.
AB  - and Response by Ryota Inokuchi, Yoshitaka Hara, Hideo Yasuda, Noritomo Itami,
      Yoshio Terada, and Kent Doi.

PMID- 29017702
TI  - Collaborative study on saccharide quantification of the Haemophilus influenzae
      type b component in liquid vaccine presentations.
AB  - Before release onto the market, it must be demonstrated that the total and free
      polysaccharide (poly ribosyl-ribitol-phosphate, PRP) content of Haemophilus
      influenzae type b (Hib) vaccine complies with requirements. However,
      manufacturers use different methods to assay PRP content: a national control
      laboratory must establish and validate the relevant manufacturer methodology
      before using it to determine PRP content. An international study was organised by
      the World Health Organization (WHO), in collaboration with the Biological
      Standardisation Programme (BSP) of the Council of Europe/European Directorate for
      the Quality of Medicines & HealthCare (EDQM) and of the European Union
      Commission, to verify the suitability of a single method for determining PRP
      content in liquid pentavalent vaccines (DTwP-HepB-Hib) containing a whole-cell
      pertussis component. It consists of HCl hydrolysis followed by chromatographic
      separation and quantification of ribitol on a CarboPac MA1 column using high
      performance anion exchange chromatography coupled with pulsed amperometric
      detection (HPAEC-PAD). The unconjugated, free, PRP is separated from the total
      PRP using C4 solid-phase extraction cartridges (SPE C4). Ten quality control
      laboratories performed two independent analyses applying the proposed analytical
      test protocol to five vaccine samples, including a vaccine lot with sub-potent
      PRP content and very high free PRP content. Both WHO PRP standard and ribitol
      reference standard were included as calibrating standards. A significant bias
      between WHO PRP standard and ribitol reference standard was observed. Study
      results showed that the proposed analytical method is, in principle, suitable for
      the intended use provided that a validation is performed as usually expected from
      quality control laboratories.

PMID- 29017703
TI  - Establishment of the Ph. Eur. Hepatitis A virus RNA for NAT testing BRP batch 1.
AB  - Detection of viral contamination in plasma donations is critical to prevent
      transmission of infectious diseases. The European Pharmacopoeia (Ph. Eur.)
      monograph 1646 'Human plasma (pooled and treated for virus inactivation)',
      requires that plasma pools used for the manufacture of this product be tested,
      among others, for the presence of hepatitis A virus RNA by nucleic acid testing
      (NAT) using a positive control containing 100 International Units (IU) of
      hepatitis A virus (HAV) RNA per mL. To this end, the European Directorate for the
      Quality of Medicines & HealthCare (EDQM, Council of Europe) organised an
      international collaborative study under the aegis of the Biological
      Standardisation Programme, for the establishment of the 1st Biological Reference
      Preparation (BRP) for HAV RNA for NAT testing. A freeze-dried candidate material
      was thus prepared and calibrated against the WHO 2nd International Standard for
      HAV for NAT (00/562) in a study in which thirteen European and North American
      laboratories including Official Medicines Control Laboratories (OMCLs),
      manufacturers of plasma-derived products, producers of in vitro diagnostic kits
      and a blood transfusion centre participated. Based on the outcome of the study,
      an HAV RNA content of 40 000 IU/vial (corresponding approximately to 4.6 log10
      IU/vial) was assigned to the BRP, which was adopted by the Ph. Eur. Commission in
      March 2016 as Ph. Eur. hepatitis A virus RNA for NAT testing BRP batch 1.

PMID- 29017704
TI  - Subungual Blue Nevus.

PMID- 29017705
TI  - Reading between the lines, the key to successfully implementing early
      rehabilitation in critical care.

PMID- 29017706
TI  - Improving uptake of colorectal cancer screening.

PMID- 29017707
TI  - Surgery in ileocaecal Crohn's disease: one more option, sometimes the best?

PMID- 29017708
TI  - Does biopsy still have a role for adult coeliac disease?

PMID- 29017709
TI  - Prognostic scores and non-invasive markers in primary sclerosing cholangitis:
      good for patients or for papers?

PMID- 29017710
TI  - Cholera outbreak in Yemen.

PMID- 29017714
TI  - Correction to Lancet Gastroenterol Hepatol 2017; 2: 32-42.

PMID- 29017715
TI  - Correction to Lancet Gastroenterol Hepatol 2017; 2: 785-92.

PMID- 29017718
TI  - Corrigendum to "House sparrows mitigate growth effects of post-natal
      glucocorticoid exposure at the expense of longevity" [Gen. Comp. Endocrinol. 253
      (2017) 1-12].

PMID- 29017719
TI  - Comparison of gamma- and DVH-based in vivo dosimetric plan evaluation for pelvic
      VMAT treatments.
AB  - BACKGROUND AND PURPOSE: To compare DVH-based quality assurance to a multi
      parametric gamma-based methodology for in vivo EPID dosimetry for VMAT to the
      pelvis. MATERIALS AND METHODS: For 47 rectum, 37 prostate, and 44 bladder VMAT
      treatments we reconstructed the 3D dose distributions of 387 fractions from in
      vivo EPID dosimetry. The difference between planned and measured dose was
      evaluated using gamma analysis (3%/3mm) in the 50% isodose volume (IDV) and DVH
      differences (DeltaD2, DeltaD50 and DeltaD98) of targets and organs at risk. The
      gamma-indicators mean gamma, gamma pass rate and gamma1% were compared to DVH
      differences and their correlations were studied. DVH-based alerts on PTV and IDV
      were compared to gamma-based alerts. RESULTS: Average PTV D50 and D98 dose
      differences were 0.0+/-2.2% (1SD) and -1.4+/-2.9% (1SD). Alert criteria of
      |DeltaD50|<3.5-4.5% corresponded to an alert rate of about 10%. Strong
      correlations between mean gamma and gamma pass rate and difference in PTV
      DeltaD50 were observed for all sites. DVH- and gamma-based alerts agreed on >80%
      of the fractions for the majority of compared alert thresholds and methods. This
      agreement is >90% for the larger deviations. CONCLUSIONS: Strong correlations
      between some gamma- and DVH indicators were found. Our comparison of multi
      parametric alert strategies showed clinical equivalence for gamma- and DVH-based
      methods.

PMID- 29017720
TI  - Insights into the molecular roles of Zika virus in human reproductive
      complications and congenital neuropathologies.
AB  - The recent upsurge in the association of congenital neurological disorders and
      infection by the Zika virus (ZIKV) has resulted in increased research focus on
      the biology of this flavivirus. Studies in animal models indicate that ZIKV can
      breach the placental barrier and selectively infect and deplete neuroprogenitor
      cells (NPCs) of the developing fetus, resulting in changes of brain structures,
      reminiscent of human microcephaly. In vitro and ex vivo studies using human cells
      and tissues showed that human NPCs and placental cells are targeted by ZIKV. Also
      of concern is the impact of ZIKV on human reproductive structures, with the
      potential to cause infertility, as the virus appears to remain in the genital
      tract for extended periods of time. This review discusses the putative roles of
      ZIKV on human reproductive complications and congenital neuropathologies.

PMID- 29017721
TI  - Varied influence of microcystin structural difference on ELISA cross-reactivity
      and chlorination efficiency of congener mixtures.
AB  - Enzyme-linked immunosorbent assay (ELISA) is an antibody-based analytical method
      that has been widely applied in water treatment utilities for the screening of
      toxic cyanobacteria metabolites such as microcystins (MCs). However, it is
      unknown how the minor structural difference of MCs may impact their chlorination
      kinetics and measurement via ELISA method. It was found in this study that,
      regardless of the experimental conditions (n = 21), there was no MC-YR or MC-LY
      residual, while different removal rates of other MCs were observed (MC-RR > MC-LR
      > MC-LA ~ MC-LF) as measured by liquid chromatography tandem mass spectrometry
      (LC-MS/MS), which was consistent with the relative reactivity of the amino acid
      variables with free chlorine. The removal of total MCs was generally lower as
      measured by ELISA than by LC-MS/MS. By incorporating both analytical results,
      existence of ADDA-containing byproducts or byproducts that had a higher
      sensitivity toward the ELISA kit was demonstrated, after excluding the
      contribution of the cross-reactivity of the parent MCs. It should be noted,
      however, that the cross-reactivities of MCs could be influenced not only by MC
      congeners, but also by other conditions such as mixtures and the applied ELISA
      kit.

PMID- 29017722
TI  - One-pot synthesis of zeolitic imidazolate framework-8/poly (methyl methacrylate
      ethyleneglycol dimethacrylate) monolith coating for stir bar sorptive extraction
      of phytohormones from fruit samples followed by high performance liquid
      chromatography-ultraviolet detection.
AB  - In this work, zeolitic imidazolate framework-8 (ZIF-8)/poly (methyl methacrylate
      ethyleneglycol dimethacrylate) (MMA-EGDMA) composite monolith was in situ
      synthesized on stir bar by one-pot polymerization. Compared with the neat
      monolith, ZIF-8/poly(MMA-EGDMA) composite monolith has larger surface area and
      pore volume. It also exhibits higher extraction efficiency for target
      phytohormones than poly(MMA-EGDMA) monolith and commercial polyethylene glycol
      (PEG) coated stir bar. Based on it, a method of ZIF-8/poly(MMA-EGDMA) monolith
      coated stir bar sorptive extraction (SBSE)-high performance liquid chromatography
      ultraviolet detection (HPLC-UV) was established for the analysis of five
      phytohormones in apple and pear samples. The developed method exhibited low
      limits of detection (0.11-0.51MUg/L), wide linear range (0.5-500MUg/L) and good
      recoveries (82.7-111%), which demonstrated good application potential of the ZIF
      8/monolith coated stir bar in trace analysis of organic compounds.

PMID- 29017723
TI  - Comparison of nanofluidic and ultra-high performance liquid chromatography-tandem
      mass spectrometry for high sensitive pharmacokinetic studies of estrogens
      starting from whole blood microsampling.
AB  - Pharmacokinetic (PK) studies on small animals are challenging as only small
      volumes of samples are available, in which the analyte is present at low
      concentration in a complex matrix. In this context, the use of miniaturized
      analytical techniques may provide undeniable advantages in terms of sensitivity,
      sample and solvent consumption compared to the reference UHPLC-MS/MS methods In
      this study, we present the development of a nanofluidic-LC-MS/MS method to
      analyze two model analytes of therapeutic interest, namely estradiol (E2) and
      estetrol (E4) after microsampling with volumetric absorptive microsampling (VAMS)
      devices, an innovative sampling technique to collect small volumes of whole
      blood. The nanofluidic LC-MS/MS method was developed using an experimental design
      to find the optimal conditions to analyze both E2 and E4 with the highest
      sensitivity. Subsequently, the optimized method was validated according to ICH
      guidelines and compared to a previously developed UHPLC-MS/MS method. A limit of
      quantitation of 50pg/ml was reached with the LC-chip method, which is 50 times
      better than UHPLC-MS/MS. Both methods were then critically evaluated from the
      analytical and operational points of view. Finally, the quantitation of estrogens
      after whole blood microsampling was compared with the results obtained with the
      corresponding plasma samples.

PMID- 29017724
TI  - Using experiential marine debris education to make an impact: Collecting debris,
      informing policy makers, and influencing students.
AB  - The Shore to Statehouse project supported the creation of an open-source,
      replicable, undergraduate experiential course on marine debris. Funded by the
      National Oceanic and Atmospheric Administration, the course allowed undergraduate
      students in Connecticut, USA, to collect marine debris locally, then create a
      policy report for state legislators. Here we share the results of the project
      including data on four accumulation surveys on the Long Island Sound, as well as
      the impact on student motivation, attitudes, and behavior levels. Results include
      finding over 1600 individual pieces of debris totaling 19.4kg (42.8lb). In
      addition, the students experienced statistically significant improvements in
      knowledge and behavior scores. This open-source course can be replicated,
      empowering students to remove debris, provide important information to local
      policy makers, and improve knowledge and behavior.

PMID- 29017725
TI  - Appropriateness of a pediatric-specific enhanced recovery protocol using a
      modified Delphi process and multidisciplinary expert panel.
AB  - PURPOSE: Despite Enhanced Recovery After Surgery (ERAS) protocols demonstrating
      improved outcomes in a wide variety of adult surgical populations, these
      protocols are infrequently and inconsistently being used in pediatric surgery.
      Our purpose was to develop a pediatric-specific ERAS protocol for use in
      adolescents undergoing elective intestinal procedures. METHODS: A modified Delphi
      process including extensive literature review, iterative rounds of surveys, and
      expert panel discussions was used to establish ERAS elements that would be
      appropriate for children. The 16-member multidisciplinary expert panel included
      surgeons, gastroenterologists, anesthesiologists, nursing, and patient/family
      representatives. RESULTS: Building upon a national survey of surgeons in which 14
      of 21 adult ERAS elements were considered acceptable for use in children, the 7
      more contentious elements were investigated using the modified Delphi process. In
      final ranking, 5 of the 7 controversial elements were deemed appropriate for
      inclusion in a pediatric ERAS protocol. Routine use of insulin to treat
      hyperglycemia and avoidance of mechanical bowel preparation were not included in
      the final recommendations. CONCLUSIONS: Using a modified Delphi process, we have
      defined an appropriate ERAS protocol comprised of 19 elements for use in
      adolescents undergoing elective intestinal surgery. Prospective validation
      studies of ERAS protocols in children are needed. LEVEL OF EVIDENCE: Level V,
      Expert opinion.

PMID- 29017726
TI  - The effect of accounting for biarticularity in hip flexor and hip extensor joint
      torque representations.
AB  - Subject-specific torque-driven models have ignored biarticular effects at the
      hip. The aim of this study was to establish the contribution of monoarticular hip
      flexors and hip extensors to total hip flexor and total hip extensor joint
      torques for an individual and to investigate whether torque-driven simulation
      models should consider incorporating biarticular effects at the hip joint.
      Maximum voluntary isometric and isovelocity hip flexion and hip extension joint
      torques were measured for a single participant together with surface
      electromyography. Single-joint and two-joint representations were fitted to the
      collected torque data and used to determine the maximum voluntary joint torque
      capacity. When comparing two-joint and single-joint representations, the single
      joint representation had the capacity to produce larger maximum voluntary hip
      flexion torque (larger by around 9% of maximum torque) and smaller maximum
      voluntary hip extension torque (smaller by around 33% of maximum torque) with the
      knee extended. Considering the range of kinematics found for jumping movements,
      the single-joint hip flexors had the capacity to produce around 10% additional
      torque, while the single joint hip extensors had about 70% of the capacity of the
      two-joint representation. Two-joint representations may overcome an over
      simplification of single-joint representations by accounting for biarticular
      effects, while building on the strength of determining subject-specific
      parameters from measurements on the participant.

PMID- 29017727
TI  - Effects of low-level prenatal exposure to dioxins on cognitive development in
      Japanese children at 42months.
AB  - BACKGROUND: Prenatal exposure to polychlorinated dibenzo-p-dioxins (PCDDs) or
      polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls
      (dioxin-like compounds [DLCs]) through environmental chemicals may affect the
      neurodevelopment of children. In our previous study, an inverse association was
      observed between prenatal DLCs and neurodevelopment of infants aged 6months in
      both sexes. However, studies are yet to determine how long these adverse effects
      last. OBJECTIVE: To examine whether the effects of DLCs on cognitive development
      remains at 42months. METHODS: In this prospective cohort study conducted in
      Sapporo, Japan, pregnant mothers' blood was analyzed for the congener level of
      DLCs. The Kaufman Assessment of Battery for Children (K-ABC) was used to test
      their children's cognitive development at 42months. A total of 141 mother-child
      pairs were included in the final analysis. The multiple linear regression
      analysis was used to examine the association between the K-ABC scores and DLC
      levels in the maternal blood. RESULTS: Seven isomers (1,2,3,6,7,8-HxCDD,
      2,3,4,7,8-PeCDF, 33'44'55'-HxCB(#169), 2344'5- PenCB(#114), 233'44'5-HexCB(#156),
      233'44'5'-HexCB(#157), 23'44'55'-HexCB(#167), total PCDF, and TEQ-PCDD, PCDF,
      PCDD/DFs levels were positively associated with the achievement score (AS) of K
      ABC. However, total non-ortho PCBs were negatively associated with the Mental
      Processing Composite Score (MPCS) of K-ABC in males. In females, increased TEQ-dl
      PCB and TEQ-PCDD/F/dl-PCB were also associated with increasing AS score.
      CONCLUSIONS: This study suggests that the negative effects of prenatal DLC
      exposure on children's cognitive development at 6months were not observed in
      children aged 42months. Regarding the sex-specific effects, AS and DLCs were
      positively correlated in females, whereas those of MPCS and DLCs were
      significantly negative in males.

PMID- 29017729
TI  - Fungal community dynamics during a marine dinoflagellate (Noctiluca scintillans)
      bloom.
AB  - Contamination and eutrophication have caused serious ecological events (such as
      algal bloom) in coastal area. During this ecological process, microbial community
      structure is critical for algal bloom succession. The diversity and composition
      of bacteria and archaea communities in algal blooms have been widely
      investigated; however, those of fungi are poorly understood. To fill this gap, we
      used pyrosequencing and correlation approaches to assess fungal patterns and
      associations during a dinoflagellate (Noctiluca scintillans) bloom. Phylum level
      fungal types were predominated by Ascomycota, Chytridiomycota, Mucoromycotina,
      and Basidiomycota. At the genus level drastic changes were observed with
      Hysteropatella, Malassezia and Saitoella dominating during the initial bloom
      stage, while Malassezia was most abundant (>50%) during onset and peak-bloom
      stages. Saitoella and Lipomyces gradually became more abundant and, in the
      decline stage, contributed almost 70% of sequences. In the terminal stage of the
      bloom, Rozella increased rapidly to a maximum of 50-60%. Fungal population
      structure was significantly influenced by temperature and substrate (N and P)
      availability (P < 0.05). Inter-specific network analyses demonstrated that
      Rozella and Saitoella fungi strongly impacted the ecological trajectory of N.
      scintillans. The functional prediction show that symbiotrophic fungi was
      dominated in the onset stage; saprotroph type was the primary member present
      during the exponential growth period; whereas pathogentroph type fungi enriched
      in decline phase. Overall, fungal communities and functions correlated
      significantly with N. scintillans processes, suggesting that they may regulate
      dinoflagellate bloom fates. Our results will facilitate deeper understanding of
      the ecological importance of marine fungi and their roles in algal bloom
      formation and collapse.

PMID- 29017728
TI  - Near-Infrared Fluorescent Proteins Engineered from Bacterial Phytochromes in
      Neuroimaging.
AB  - Several series of near-infrared (NIR) fluorescent proteins (FPs) were recently
      engineered from bacterial phytochromes but were not systematically compared in
      neurons. To fluoresce, NIR FPs utilize an enzymatic derivative of heme, the
      linear tetrapyrrole biliverdin, as a chromophore whose level in neurons is poorly
      studied. Here, we evaluated NIR FPs of the iRFP protein family, which were
      reported to be the brightest in non-neuronal mammalian cells, in primary neuronal
      culture, in brain slices of mouse and monkey, and in mouse brain in vivo. We
      applied several fluorescence imaging modes, such as wide-field and confocal one
      photon and two-photon microscopy, to compare photochemical and biophysical
      properties of various iRFPs. The iRFP682 and iRFP670 proteins exhibited the
      highest brightness and photostability under one-photon and two-photon excitation
      modes, respectively. All studied iRFPs exhibited efficient binding of the
      endogenous biliverdin chromophore in cultured neurons and in the mammalian brain
      and can be readily applied to neuroimaging.

PMID- 29017730
TI  - Discussion of: "Southwestern Surgical Congress Jack A. Barney award competition
      presenters - Where are they now?"

PMID- 29017731
TI  - Impact of geriatric consultations on clinical outcomes of elderly trauma
      patients: A retrospective analysis.
AB  - INTRODUCTION: The elderly account for a large proportion of morbidity and
      mortality secondary to trauma, despite lower-energy mechanisms of injury and
      fewer trauma admissions. The benefit of geriatric trauma consultation services
      (GTCS) to this population remains unclear. METHODS: We performed a retrospective
      cohort analysis of a GTCS, which was established in January 2015. Patients over
      60 admitted to the trauma service from January of 2014 to February 2016 were
      eligible. RESULTS: There were no significant differences in 30-day and in
      hospital mortalities, mean ICU and total lengths of stay, or complication rates.
      However, if a single complication was experienced, post-GTCS patients were nearly
      three times more likely to experience multiple complications. More patients in
      the GTCS group were discharged home, but were readmitted four times more often.
      CONCLUSIONS: A mandatory GTCS was not associated with improved patient outcomes,
      suggesting that management exclusively by the trauma team is at least equally
      effective in treatment of geriatric trauma.

PMID- 29017732
TI  - A nationwide evaluation of robotic ventral hernia surgery.
AB  - BACKGROUND: The purpose of this study was to examine outcomes of robotic ventral
      hernia repair(RVHR) versus laparoscopic ventral hernia repair(LVHR). METHODS: The
      Nationwide Inpatient Sample was queried from October 2008 to December 2013 for
      ventral hernia repairs. Demographics, morbidity, mortality, and charges were
      compared between RVHR and LVHR. RESULTS: From 2008-2013, 149,622 ventral hernia
      surgeries were identified; 117,028 open, 32,243 laparoscopic, and 351 robotic.
      Open repairs were excluded. RVHR rose annually with 2013 containing 47.9% of all
      RVHRs. RVHR patients were more likely to be older and have more chronic
      conditions. There was no difference between length of stay. Pneumonia rates were
      higher with RVHR; however, after controlling for confounding variables, there was
      no difference in pneumonia rates. Mortality and other major complications were
      similar. Total charges were increased for RVHR in univariate and multivariate
      analysis. RVHR was more common in teaching hospitals and wealthier zip codes.
      CONCLUSION: RVHR demonstrates comparable safety to the laparoscopic technique,
      with increased charges and increased volume in urban teaching hospitals and
      patients from areas of higher median income.

PMID- 29017733
TI  - Re: Heat generation and drill wear during dental implant site preparation.

PMID- 29017734
TI  - Anatomy of the vasculature of the lower leg and harvest of a fibular flap: a
      systematic review.
AB  - The fibular free flap (FFF) is based on the peroneal artery, which has a
      consistent anatomy and makes a minimal contribution to the pedal circulation.
      However, certain anatomical variations in the vasculature of the leg might leave
      the peroneal artery with a major role in the perfusion of the foot, and to raise
      a FFF could lead to ischaemic complications. Our aim was to review the
      implications of anatomical variants on planning and harvest of a FFF. We
      systematically reviewed all relevant publications, and included 28 cases that
      described a dominant peroneal artery and FFF. Most of the patients had clinically
      normal pulses, and the dominant peroneal artery was diagnosed by preoperative
      vascular mapping. Variants of the peronea arteria magna were the most common.
      Bilateral anatomical variations were reported in 10 cases. The surgical plan to
      harvest the fibula was altered in 21 patients with vascular aberrations. In 17 of
      the 21, the leg with the anatomical variant was not used. The opposite fibula was
      used in 10 cases. In four of the 21, the FFF was harvested from the leg with a
      dominant peroneal artery, after the technique of harvest had been modified. The
      FFF was successfully harvested without any modification in only five cases. Two
      patients who had not had preoperative vascular mapping developed acute ischaemia
      of the limb after harvest of the FFF because of an existing peronea arteria
      magna. Preoperative vascular mapping is a valuable way to assess that perfusion
      of the foot is adequate, and it provides accurate information about the vascular
      anatomy, cutaneous perforators, and the fibular blood supply, with minimal or no
      added cost or risks.

PMID- 29017735
TI  - Re: re: Heat generation and drill wear during dental implant site preparation:
      systematic review.

PMID- 29017736
TI  - Chronic recurrent dislocation of the temporomandibular joint secondary to a
      complex facial tic disorder.

PMID- 29017737
TI  - Laparoscopic adenomectomy: 10 years of experience.
AB  - INTRODUCTION: Lower urinary tract symptoms secondary to increased prostate volume
      are associated with ageing and are becoming more prevalent due to increased life
      expectancy. We present our experience with transperitoneal laparoscopic
      adenomectomy for the management of bladder outlet obstruction caused by benign
      prostatic enlargement. MATERIALS AND METHODS: We performed a retrospective review
      of patients who underwent laparoscopic adenomectomy between 2005 and 2015. We
      recorded age, maximum flow and postvoid residual urine (preoperative and
      postoperative), surgical time, operative bleeding, weight and pathology,
      complications and duration of catheterisation and hospitalisation. RESULTS: We
      included 80 patients with a mean age of 70 years. The mean preoperative and
      postoperative Qmax was 8.21mL/s and 22.52mL/s, respectively. The mean
      preoperative and postoperative postvoid residual urine was 91.4mL and 14.2mL,
      respectively. The mean surgical time was 137.7min. Conversion to open surgery was
      necessary in one case due to intestinal injury. The mean intraoperative bleeding
      was 227.6mL. The mean hospital stay was 5.46 days, and the catheterisation time
      was 4.86 days. There were 13 complications, which were recorded according to the
      Clavien-Dindo system, 3 of which were severe. The mean weight of the surgical
      specimen was 80.02g. Pathology showed benign hyperplasia in 75 cases and prostate
      cancer in the remaining 5. CONCLUSION: Laparoscopic adenomectomy is a safe,
      reproducible technique with the same functional results as open surgery. Our
      series shows that this approach is useful and safe and has a low rate of
      complications.

PMID- 29017739
TI  - Pulmonary and laryngeal tuberculosis in a 25-weeks' gestation parturient,
      diagnosed after failed tracheal intubation.
AB  - A pregnant woman at 25weeks of gestation was diagnosed with laryngeal
      tuberculosis following a failed intubation for upper gastrointestinal endoscopy.
      Laryngeal tuberculosis represents approximately 1% of all cases of tuberculosis
      in the United States and presents a unique diagnostic challenge, because
      accompanying laryngeal changes are both varied and nonspecific. This report
      highlights both the challenges of the pregnant airway and the diagnosis and
      treatment of laryngeal tuberculosis.

PMID- 29017738
TI  - The burden of atopic dermatitis in US adults: Health care resource utilization
      data from the 2013 National Health and Wellness Survey.
AB  - BACKGROUND: There is a lack of data on the burden of atopic dermatitis (AD) in
      adults relative to the general population. OBJECTIVE: To characterize the AD
      burden in adult patients relative to both matched non-AD controls and matched
      patients with psoriasis in terms of comorbidities, health care resource
      utilization (HCRU), and costs. METHODS: Adults (>=18 years) who self-reported a
      diagnosis of AD or psoriasis and adult non-AD controls were identified from the
      2013 US National Health and Wellness Survey. Patients with AD were propensity
      score-matched with non-AD controls and patients with psoriasis on demographic
      variables. Patient-reported outcomes were analyzed between matched cohorts.
      RESULTS: Patients with AD had a significantly greater risk for atopic
      comorbidities, as well as significantly greater HCRU and total cost compared with
      non-AD controls. The burden of AD was generally comparable to that of psoriasis,
      although patients with AD reported increased use of emergency room visits
      compared with patients with psoriasis. LIMITATIONS: Patient-reported data are
      susceptible to recall bias and erroneous classification. CONCLUSIONS: Adult
      patients with AD reported a substantial disease burden, suggesting an unmet need
      for more effective AD treatment options.

PMID- 29017740
TI  - Evaluation of the Genesis Epidural-Spinal Injection Simulator.

PMID- 29017741
TI  - How to replace fibrinogen in postpartum haemorrhage situations? (Hint: Don't use
      FFP!).

PMID- 29017742
TI  - Preoperative anterior thigh temperature does not correlate with perioperative
      temporal hypothermia during cesarean delivery with spinal anesthesia: Secondary
      analysis of a randomized control trial.
AB  - BACKGROUND: Core-to-peripheral redistribution of heat, secondary to sympathetic
      mediated vasodilation, is the major mechanism leading to early perioperative
      hypothermia after neuraxial anesthesia. The study aim was to determine if
      preoperative anterior thigh (peripheral lower extremity) temperature predicted
      perioperative temporal (core) temperature decrease during cesarean delivery with
      spinal anesthesia. METHODS: Secondary analysis of data derived from a
      prospective, randomized study of 46 healthy women undergoing scheduled cesarean
      delivery with spinal anesthesia was performed. Anterior thigh temperature was
      measured preoperatively prior to spinal anesthesia. The primary outcome was
      maximum perioperative temporal temperature decrease. Secondary outcomes included
      incidence of temporal hypothermia (temperature <36 degrees C), shivering, and
      thermal comfort scores. This study ran concurrently with a previously published
      trial comparing no active intraoperative warming with active warming. RESULTS:
      There was no correlation between preoperative anterior thigh temperature and
      maximum perioperative temporal temperature decrease (r=-0.049, P=0.751). The
      mean+/-standard deviation preoperative anterior thigh temperature of women who
      developed temporal hypothermia compared to those who did not was 32.4+/-0.8
      degrees C versus 32.4+/-0.70 degrees C respectively (P=0.995). Preoperative
      anterior thigh temperature did not correlate with the incidence of shivering
      (r=0.267, P=0.080) or thermal comfort scores (r=0.233, P=0.129). CONCLUSION:
      Preoperative anterior thigh temperature does not correlate with the degree of
      perioperative temporal temperature decrease, likelihood of developing
      hypothermia, shivering, or thermal comfort during cesarean delivery with spinal
      anesthesia. Although core-to-peripheral redistribution of heat after neuraxial
      anesthesia is a major mechanism of perioperative heat loss, a lower extremity
      temperature prediction hypothesis was not confirmed in this population.

PMID- 29017743
TI  - Resistance training for rehabilitation after burn injury: A systematic literature
      review & meta-analysis.
AB  - BACKGROUND/AIM: Resistance training is beneficial for rehabilitation in many
      clinical conditions, though this has not been systematically reviewed in burns.
      The objective was to determine the effectiveness of resistance training on muscle
      strength, lean mass, function, quality of life and pain, in children and adults
      after burn injury. METHODS: Medline & EMBASE, PubMed, CINAHL and CENTRAL were
      searched from inception to October 2016. Studies were identified that implemented
      resistance training in rehabilitation. Data were combined and included in meta
      analyses for muscle strength and lean mass. Otherwise, narrative analysis was
      completed. The quality of evidence for each outcome was summarised and rated
      using the GRADE framework. RESULTS: Eleven studies matched our inclusion
      criteria. Primary analysis did not demonstrate significant improvements for
      increasing muscle strength (SMD 0.74, 95% CI -0.02 to 1.50, p=0.06). Sensitivity
      analysis to correct an apparent anomaly in published data suggested a positive
      effect (SMD 0.37, 95% CI 0.08-0.65, p=0.01). Psychological quality of life
      demonstrated benefit from training (MD=25.3, 95% CI 3.94-49.7). All studies were
      rated as having high risk of bias. The quality of the evidence was rated as low
      or very low. CONCLUSION: Further research with robust methodology is recommended
      to assess the potential benefit suggested in this review.

PMID- 29017744
TI  - Effect of season on follicular population, quality and nuclear maturation of
      bovine oocytes under tropical conditions.
AB  - The aim was to determine the effect of season of the year and the presence of a
      corpus luteum (CL) on follicular population (FP) and the quality of the oocytes,
      and of season on nuclear maturation of the bovine oocytes under tropical
      conditions. Three seasons were evaluated: hot-dry (March-June), hot-humid (July
      October) and fresh-humid (November-February). In a first study, 1112 bovine
      ovaries were obtained from a local slaughterhouse. Follicles were classified as
      small (<=4mm), middle (4.1-8mm) and large (>=8.1mm); and the maximum diameter of
      the follicle (MDF) and CL (MDCL) were also recorded. The oocytes were collected
      by aspiration and classified as viable (grade I and II) and damaged (grade III
      and IV). In the second study, 2261 viable oocytes were matured in vitro, and then
      fixed and stained with Lacmoid to classify the stage of development as mature
      (metaphase II), immature or degenerate. Data were analyzed using analysis of
      variance and chi-square procedures. The largest FP of large follicles (0.67), MDF
      (1.18mm), MDCL (1.87mm), and the highest proportion of viable oocytes (34.19%)
      were obtained during the hot-humid season (P<0.05). The ovaries without CL had
      the greatest FP (10.34) with more viable oocytes (24.44%). The highest proportion
      of mature oocytes (76.92%) was also obtained in the hot-humid season. In
      conclusion, season influenced FP, MDF, MDCL, and the quality and nuclear
      maturation of oocytes. The presence of a CL in the ovary resulted in a decrease
      of FP and viability of oocytes.

PMID- 29017745
TI  - Does transcutaneous nerve stimulation have effect on sympathetic skin response?
AB  - OBJECTIVE: This study examined the effects of transcutaneous electrical nerve
      stimulation (TENS) on the sympathetic nerve system by sympathetic skin response
      test. METHODS: Fifty-five healthy volunteers received either: (i) 30minutes TENS
      (25 participants) (ii) 30minutes sham TENS (30 participants) and SSR test was
      performed pre- and post-TENS. The mean values of latency and peak-to-peak
      amplitude of five consecutive SSRs were calculated. RESULTS: A significant
      amplitude difference was found between TENS and sham TENS group both in right and
      left hand (p=0.04, p=0.01, respectively). However there was no significant
      latancy difference between two groups (p>0.05 ). CONCLUSION: TENS has an
      inhibitory effect on elicited SNS responses when compared with sham TENS control
      group.

PMID- 29017746
TI  - Mild water restriction with or without urea for the longterm treatment of
      syndrome of inappropriate antidiuretic hormone secretion (SIADH): Can urine
      osmolality help the choice?
AB  - BACKGROUND: Treatment options for chronic SIADH include water restriction (WR)
      and urea. The usefulness of urine osmolality to guide the choice of the treatment
      option is not clearly defined. We hypothesized that urine osmolality can indicate
      whether treatment with mild water restriction alone could be successful. METHODS:
      Retrospective Review of clinical and biochemical (blood and urine) data of
      patients with chronic SIADH treated for at least one year with mild WR (1.5
      2l/day) either with or without urea. RESULTS: Twenty nine patients were included.
      Nine patients were treated by mild WR. Mean serum sodium (SNa) and mean Uosm were
      129+/-2mEq/l and 274+/-78mOsm/kgH2O respectively before WR, and increased to
      138.5+/-3mEq/l and 505+/-87mOsm/kgH2O (P<0.001). Eight patients were treated with
      mild WR and 15g urea daily, the SNa and Uosm before treatment were 127.5+/-3mEq/l
      and 340+/-100mOsm/kgH2O respectively and increased to 136.5+/-1mEq/l and 490+/
      151mOsm/kgH2O (P<0.001). Four of the eight patients had a permanent low solute
      intake which contributed to hyponatremia. Twelve patients needed 30g urea daily
      combined with mild WR. The SNa and Uosm were respectively 126+/-2mEq/l and 595+/
      176mOsm/kgH2O and increased to 136.5+/-2mEq/l and 698+/-157mOsm/kgH2O (P<0.05).
      Uosm increased in most of the treated patients. CONCLUSIONS: About 30% of
      patients could be treated by moderate WR alone. All these patients presented an
      initial urine osmolality lower than 400mOsm/kgH2O.

PMID- 29017747
TI  - Re: "Lesson Learned with the Use of Iliac Branch Devices: Single Centre 10 Year
      Experience in 157 Consecutive Procedures".

PMID- 29017748
TI  - Transcatheter Aortic Valve Implantation In Patients With a Large Aortic Annulus.
AB  - BACKGROUND: As the indications for transcatheter aortic valve implantation (TAVI)
      have expanded, so to have the demands on interventionists to allow as many
      patients to access this technology as possible. METHODS: We retrospectively
      reviewed our TAVI database for patients who had received a 29mm SAPIEN 3 valve
      despite having an annular area greater than the manufacturer-recommended upper
      limit of 683mm2, as determined by multi-detector computed tomography (MDCT).
      Procedural and inpatient outcome data were collected. RESULTS: The study
      population was 5 of 121 patients receiving a SAPIEN 3 valve since it became
      available in March 2015. Their annular area ranged from 691 to 800mm2. Valve
      deployment was successful in all patients. The deployment balloon volume was
      nominal, except for an additional 1ml in one patient. No patient had a new
      indication for permanent pacing, and no significant valvular or paravalvular
      regurgitation (PVR) was identified on post-procedure transthoracic
      echocardiography. All patients survived to hospital discharge. CONCLUSIONS: In
      this select group of patients we have demonstrated that it is safe and feasible
      to use the 29mm SAPIEN 3 in patients with annular dimensions greater than those
      recommended, with minimal balloon overfilling.

PMID- 29017749
TI  - Characterization of the nuclear import pathway for BLM protein.
AB  - Numerous studies have shown that nuclear localization of BLM protein, a member of
      the RecQ helicases, mediated by nuclear localization signal (NLS) is critical for
      DNA recombination, replication and transcription, but the mechanism by which BLM
      protein is imported into the nucleus remains unknown. In this study, the nuclear
      import pathway for BLM was investigated. We found that nuclear import of BLM was
      inhibited by two dominant-negative mutants of importin beta1 and NTF2/E42K, which
      lacks the ability to bind Ran and RanGDP, respectively, but was not inhibited by
      the Ran/Q69L, which is deficient in GTP hydrolysis. Further studies revealed that
      nuclear import of BLM was reconstituted using importin beta1, RanGDP and NTF2 in
      digitonin-permeabilized HeLa cells. Moreover, BLM had direct binding to importin
      beta1 through its NLS domain with the 14-16 HEAT repeats of importin beta1.
      Furthermore, importin beta1, Ran or NTF2 depletion by siRNA disrupted the
      accumulation of BLM protein in the nucleus. These results showed that BLM enters
      the nucleus via the importin beta1, RanGDP and NTF2 dependent pathway,
      demonstrating for the first time the nuclear trafficking mechanism of a DNA
      helicase.

PMID- 29017750
TI  - Trends and relationship between antimicrobial resistance and antibiotic use in
      Xinjiang Uyghur Autonomous Region, China: Based on a 3 year surveillance data,
      2014-2016.
AB  - PURPOSES: The objective of the study was to identify the trends and relations
      between antimicrobial resistance (AMR) and antibiotic use in the Xinjiang Uyghur
      Autonomous Region in Western China from 2014 to 2016. METHODS: A retrospective,
      descriptive analysis of AMR prevalence, and trends and relations between AMR and
      antibiotic use during the 3-year period was performed. RESULTS: Third-generation
      cephalosporin-resistant Escherichia coli was the most prevalent resistant
      pathogen in terms of both resistance density and resistance proportion. A
      significant correlation was found between resistance density of third-generation
      cephalosporin-resistant Klebsiella pneumoniae and the use of beta-lactam-beta
      lactamase inhibitor combinations (cc=0.63, p=0.03), quinolones (cc=0.60, p=0.04),
      and carbapenems (cc=0.76, p=0.004), among which only beta-lactam-beta-lactamase
      inhibitor combinations showed a significant correlation with third-generation
      cephalosporin-resistant E. coli (cc=0.63, p=0.03). For carbapenem-resistant
      Pseudomonas aeruginosa, not only carbapenem use (cc=0.65, p=0.02) but also
      penicillin (cc=0.76, p=0.004) and quinolone (cc=0.69, p=0.01) use showed
      significant correlation. A strong correlation was observed between the resistant
      proportion of third-generation cephalosporin-resistant E. coli and only the use
      of beta-lactam-beta-lactamase inhibitor combinations (cc=0.61, p=0.03).
      CONCLUSION: The association between antibiotic use and AMR, especially the
      implication of the difference in resistance density and resistance proportion, is
      crucial for local physicians and decision-makers to better use of antibiotics and
      allocate healthcare resources more effectively, as well as to better implement
      antimicrobial stewardship and effective infection control strategies.

PMID- 29017751
TI  - Varicella infection in a non-universally vaccinated population: Actual
      epidemiology in Bulgaria (2013-2015).
AB  - BACKGROUND: Varicella is a common and usually mild disease but it has great
      importance in regard to general infectious morbidity. The current study aimed to
      characterize possible risk factors of varicella epidemiology in Bulgaria, a
      country where infection follows its natural epidemiological pattern as no
      mandatory or recommended vaccine is currently applied. METHODS: Administrative
      regions of Bulgaria were used as units of observation and a set of
      sociodemographic and economic determinants, as well as geographic location (south
      or north) were tested for associations with the mean 3-year varicella incidence
      rates (2013-2015). RESULTS: The proportion of urban population, proportion of
      females, number of health care units and proportion of urban population aged <10
      years were the four sociodemographic variables most strongly and significantly
      correlated (p<0.05) with varicella frequency (Spearman's rank correlation
      coefficients of 0.62, 0.47, 0.43, and 0.38, respectively). After reducing the
      number of intercorrelated factors to a few principal components and accounting
      for confounders, the demographic component and geographic location remained most
      robustly associated with varicella incidence in Bulgaria (adjusted R2 of 0.51,
      p<0.001). CONCLUSIONS: The results obtained identify important determinants in
      the local epidemiology of varicella and show that community characteristics
      should be considered, to improve our understanding of varicella distribution.

PMID- 29017752
TI  - [Shortages in medicinal products in a tertiary care hospital in Spain].

PMID- 29017753
TI  - [Less is not more, but it can be the beginning of the change].

PMID- 29017754
TI  - Health Behavior and Quality of Life Outcome in Breast Cancer Survivors:
      Prevalence Rates and Predictors.
AB  - PURPOSE: Health behavior (HB) has been identified as contributing to breast
      cancer (BC) disease outcome. The present study was subjected to gain more in
      depth insight into breast cancer survivors' (BCS) HB and its associations with
      patient quality of life (QOL) outcome. We investigated HB focusing on eating
      disturbances comparing the latter with a reference population sample (PS).
      MATERIALS AND METHODS: The research cohort included 303 BCS completing a
      comprehensive patient-reported-outcome assessment on HB (eating disturbances,
      exercise, substance use) and QOL. Data from an age- and education-matched
      reference PS (n = 303) on eating disturbances were included. RESULTS: Overall,
      30% of BCS were overweight; 11.7% of BCS (2-11 years after diagnosis, mean = 5.2
      years) reported eating disturbances compared with 5% of PS (P < .05).
      Approximately three-fourths of BCS indicated they exercise regularly, one-fourth
      smoke regularly, and 30% consume alcohol. Lower consumption of analgesics and
      tranquilizers, higher frequency of exercise, lower eating concern (EDE-Q),
      younger age, and lower body mass index were significant predictors for better
      physical QOL. Lower eating and shape concern were next to age-identified
      predictive for better psychological QOL. DISCUSSION: Obesity and eating
      disturbances are a considerable HB problem in women with a history of BC.
      Considering that HB is predictive for long-term QOL in BCS, routine counseling on
      HB should be integrated into survivorship care to increase patient education and
      contribute to behavioral changes.

PMID- 29017755
TI  - Self-medication and non-prescription drug counseling: Illustrating profession
      uncertainty within Turkish pharmacy practice.
AB  - BACKGROUND: Recommending effective minor ailment treatments and using non
      prescription or over-the-counter (OTC) medicines is a pharmacist's duty. Although
      common in most European countries, self-medication counseling practices may
      differ from country to country. OBJECTIVES: This study explored Turkish community
      pharmacists' attitudes concerning the present self-medication market,
      professional responsibilities toward patients' self-care, and the usefulness of e
      learning for patients' counseling education. METHODS: The study was comprised of
      three phases: initially, a document content analysis searched for relevant OTC
      regulatory and/or practice frameworks; secondly, qualitative individual
      interviews on self-medication with purposively selected Turkish community
      pharmacists were performed; finally, a focus group with practitioners and
      continuing education experts was conducted to deepen previous results. A thematic
      data analysis, based on the attitudinal theory, was conducted, supported by
      MAXQDA v12 software. RESULTS: Sixteen documental sources allowed the extraction
      of three initial main themes: self-medication, classification of medicines and
      pharmacists' role. Individual interviews outlined four themes that informed the
      focus group discussion, which produced four new themes. Themes and their codes
      reflected dissimilar practitioners' cognitions towards OTCs, OTC usage and self
      medication, particularly if compared to other European conceptualizations.
      Contradictory feelings towards the value of OTCs for professional development,
      e.g., patient counseling influenced by profit-based expectations, were
      identified. CONCLUSION: Turkish community pharmacists and their minor ailments
      treatment competences have yet to thrive as a relevant professional intervention.
      There are risks of missing the best pharmacy practice standards, thus losing
      their contribution to rational self-care. Besides weakening the societal
      recognition of the profession to help individuals' everyday health decisions and
      well-being, there might be a reduced active role in public health.

PMID- 29017756
TI  - Biomechanical strain-induced modulation of proliferation coincides with an ERK1/2
      independent nuclear YAP localization.
AB  - Biomechanical strain induces activation of the transcriptional co-activator yes
      associated protein (YAP) by nuclear re-distribution. Recent findings indicate
      that the mechanically responsive mitogen-activated protein kinase (MAPK)
      extracellular signal-regulated kinase (ERK) 1/2 is involved in the amount of
      nuclear YAP, reflecting its activation. In this context, we conducted experiments
      to detect how biomechanical strain acts on the subcellular localization of YAP in
      periodontal cells. To this end, cells were subjected to 2.5% static equiaxial
      strain for different time periods. Western blot and fluorescence imaging-based
      analyses revealed a clear modulation of nuclear YAP localization. This modulation
      fairly coincided with the altered course of the KI-67 protein amount in
      conjunction with the percentage of KI-67-positive and thus proliferating cells.
      The inhibition of the ERK1/2 activity via U0126 yielded an unchanged strain
      related modulation of nuclear YAP localization, while YAP amount in whole cell
      extracts of strained cells was decreased. Administration of the YAP-inhibiting
      drug Verteporfin evoked a clear reduction of KI-67-positive and thus
      proliferating cells by approximately 65%, irrespective of strain. Our data reveal
      YAP as a regulator of strain-modulated proliferation which occurs in a MAPK
      independent fashion.

PMID- 29017758
TI  - In vitro and in vivo pharmacological characterization of ASP8477: A novel highly
      selective fatty acid amide hydrolase inhibitor.
AB  - Although exogenous agonists for cannabinoid (CB) receptors are clinically
      effective for treating chronic pain, global activation of brain CB receptors
      causes frequent central nervous system (CNS) side-effects. Fatty acid amide
      hydrolase (FAAH) is a primary catabolic enzyme for anandamide (AEA), an
      endogenous CB. Recently, we discovered a novel FAAH inhibitor, 3-pyridyl 4
      (phenylcarbamoyl)piperidine-1-carboxylate (ASP8477). In vitro studies
      demonstrated that ASP8477 inhibited human FAAH-1, FAAH-1 (P129T) and FAAH-2
      activity with IC50 values of 3.99, 1.65 and 57.3nM, respectively. ASP8477 at 10uM
      had no appreciable interactions with 65 different kinds of receptors, ion
      channels, transporters and enzymes, including CB1 and CB2 receptors and
      monoacylglycerol lipase. In adolescent rats, orally administered ASP8477 (0.3
      10mg/kg) elevated AEA concentrations in both plasma and brain. In a capsaicin
      induced secondary hyperalgesia model, a pretreatment with ASP8477 significantly
      improved mechanical allodynia and thermal hyperalgesia at 0.3-3mg/kg p.o. ASP8477
      also significantly improved mechanical allodynia in an L5/L6 spinal nerve
      ligation neuropathic pain model, with an ED50 value of 0.63mg/kg, and in a
      streptozotocin-induced diabetic neuropathy model at 3 and 10mg/kg p.o.
      Furthermore, ASP8477 significantly attenuated the reduction in rearing events at
      1 and 3mg/kg p.o. in a monoiodoacetic acid-induced osteoarthritis model.
      Importantly, ASP8477 had no significant effect on motor coordination up to
      30mg/kg p.o. These results indicate that ASP8477 is a potent, selective, and oral
      active FAAH inhibitor with activity in the CNS, with the potential to be a new
      analgesic agent with a wide safety margin.

PMID- 29017757
TI  - Effects of retinoic acid signaling on extraocular muscle myogenic precursor cells
      in vitro.
AB  - One major difference between limb and extraocular muscles (EOM) is the presence
      of an enriched population of Pitx2-positive myogenic precursor cells in EOM
      compared to limb muscle. We hypothesize that retinoic acid regulates Pitx2
      expression in EOM myogenic precursor cells and that its effects would differ in
      leg muscle. The two muscle groups expressed differential retinoic acid receptor
      (RAR) and retinoid X receptor (RXR) levels. RXR co-localized with the Pitx2
      positive cells but not with those expressing Pax7. EOM-derived and LEG-derived
      EECD34 cells were treated with vehicle, retinoic acid, the RXR agonist
      bexarotene, the RAR inverse agonist BMS493, or the RXR antagonist UVI 3003. In
      vitro, fewer EOM-derived EECD34 cells expressed desmin and fused, while more LEG
      derived cells expressed desmin and fused when treated with retinoic acid compared
      to vehicle. Both EOM and LEG-derived EECD34 cells exposed to retinoic acid showed
      a higher percentage of cells expressing Pitx2 compared to vehicle, supporting the
      hypothesis that retinoic acid plays a role in maintaining Pitx2 expression. We
      hypothesize that retinoic acid signaling aids in the maintenance of large numbers
      of undifferentiated myogenic precursor cells in the EOM, which would be required
      to maintain EOM normalcy throughout a lifetime of myonuclear turnover.

PMID- 29017759
TI  - Differential cytotoxic effects on odontoblastic cells induced by self-adhesive
      resin cements as a function of the activation protocol.
AB  - OBJECTIVES: To evaluate the cytotoxic effects of exposing odontoblast cells to a
      variety of commercial self-adhesive cements polymerized using different
      activation modes. METHODS: Five cements: MaxCem Elite (MAX), Bifix SE (BSE), G
      Cem LinkAce (GCE), Clearfil SA Luting (CAS), and RelyX U200 (U200) were mixed,
      dispensed into molds, and distributed in groups, according to polymerization
      protocols: immediate photoactivation; delayed photoactivation (10min self-curing
      plus light-activation); and chemical activation (no light exposure). Immortalized
      rat odontoblast cells (MDPC-23) were cultured. Cell viability was assessed by
      Trypan Blue staining and total cell death was assessed by annexin V-APC/7-AAD
      double staining and flow cytometry. Volatilized compounds from polymerized
      specimens of cements were evaluated by gas chromatography/mass spectrometry (GC
      MS). Data was analyzed with 2-way ANOVA/Tukey tests (alpha=0.05). RESULTS:
      Exposure to all of the cements tested significantly reduced the cell viability,
      irrespective of the activation protocol (p<0.05). The least harmful cements were
      CSA and U200. Total death of cells significantly increased when exposed to BSE,
      GCE, and MAX, especially when chemically activated (p<0.05). Characteristic
      apoptotic cells increased after exposure to cements, mainly for MAX, regardless
      of the activation mode. Chemical activation of MAX also induced necrosis.
      Moreover, GCE and MAX exhibited higher percentages of late apoptotic/dead cells.
      Chromatograms revealed 28 compounds released from the cements tested, some of
      them with known carcinogenic effects. Selection of self-adhesive cements and
      polymerization protocols affect the cytotoxicity and cell viability of
      odontoblastic cells. CLINICAL SIGNIFICANCE: Despite the simplified cementation
      protocol, care is needed when cementing indirect restorations with self-adhesive
      cements, especially on recently exposed dentin. This category of material may
      cause differential cytotoxic effects and should be considered when selecting a
      cement. This is particularly true in clinical cases of light attenuation, where
      the polymerization depends on chemical activation, inducing higher cytotoxic
      damages when using some of the cements tested.

PMID- 29017760
TI  - Mixed-mode fracture toughness of texturized LS2 glass-ceramics using the three
      point bending with eccentric notch test.
AB  - Here we use the 3-point bending with eccentric notch test (3-PBEN) to investigate
      the fracture behavior of a pressable and a CAD/CAM lithium disilicate (LS2) glass
      ceramics under combined mode-I and mode-II loading. The effect of the bulk
      texturization in the beams of the pressable LS2 is made visible through the
      fracture trajectory following the most energetically favorable path dictated by
      the crystallite alignment. The CAD/CAM LS2 shows an isotropic fracture mode but
      increasing fracture energy with mode-II contribution, similar to the pressable
      variant.

PMID- 29017761
TI  - ADM guidance-ceramics: Fatigue principles and testing.
AB  - BACKGROUND: Clinical failure of dental ceramics is usually reported as partial
      fracture of the restoration (chipping) or as catastrophic fracture of the whole
      structure. In contrast to metals, ceramics are linear-elastic, brittle materials
      exhibiting extremely low damage tolerance to failure. Well documented clinical
      and lab reports have shown this fracture event often occurs at loads far below
      their fracture strength due to intrinsic fatigue degradation via slow crack
      growth or cyclic fatigue mechanisms. The presence and development of surface
      flaws have a dominant role in damage accumulation and lifetime reduction of
      ceramic structures. AIMS: This ADM guidance document aims to summarize the
      aspects related to fatigue degradation of dental ceramics, reviewing the concepts
      of fatigue testing and furthermore aims to provide practical guidance to young
      scientists entering into fatigue related research. The description of fatigue
      strength is always accompanied by a clear understanding of the underlying
      fracture mechanisms.

PMID- 29017762
TI  - Occlusal loading during biting from an experimental and simulation point of view.
AB  - OBJECTIVES: Occlusal loading during clenching and biting is achieved by the
      action of the masticatory system, and forms the basis for the evaluation of the
      functional performance of prosthodontic and maxillofacial components. This review
      provides an overview of (i) current bite force measurement techniques and their
      limitations and (ii) the use of computational modelling to predict bite force. A
      brief simulation study highlighting the challenges of current computational
      dental models is also presented. METHODS: Appropriate studies were used to
      highlight the development and current bite force measurement methodologies and
      state-of-the-art simulation for computing bite forces using biomechanical models.
      RESULTS: While a number of strategies have been developed to measure occlusal
      forces in three-dimensions, the use of strain-gauges, piezo-electric sensors and
      pressure sheets remain the most widespread. In addition to experimental-based
      measurement techniques, bite force may be also estimated using computational
      models of the masticatory system. Simulations of different bite force models
      clearly show that the use of three-dimensional force measurements enriches the
      evaluation of masticatory functional performance. SIGNIFICANCE: Hence, combining
      computational modelling with three-dimensional force measurement techniques can
      significantly improve the evaluation of masticatory system and the functional
      performance of prosthodontic components.

PMID- 29017763
TI  - Modulating fat digestion through food structure design.
AB  - Dietary fats and oils are an important component of our diet and a significant
      contributor to total energy and intake of lipophilic nutrients and bioactives. We
      discuss their fate in a wide variety of engineered, processed and naturally
      occurring foods as they pass through the gastrointestinal tract and the implicit
      role of the food matrix within which they reside. Important factors that control
      fat and oil digestion include: 1) Their physical state (liquid or solid); 2)
      Dispersion of oil as emulsion droplets and control of the interfacial structure
      of emulsified oils; 3) The structure and rheology of the food matrix surrounding
      dispersed oil droplets; and 4) Alteration of emulsified oil droplet size and
      concentration. Using examples based on model foods such as emulsion gels and
      everyday foods such as almonds and cheese, we demonstrate that food structure
      design may be used as a tool to modulate fat and oil digestion potentially
      resulting in a number of targeted physiological outcomes.

PMID- 29017764
TI  - DNA methylation and antipsychotic treatment mechanisms in schizophrenia: Progress
      and future directions.
AB  - Antipsychotic response in schizophrenia is a complex, multifactorial trait
      influenced by pharmacogenetic factors. With genetic studies thus far providing
      little biological insight or clinical utility, the field of pharmacoepigenomics
      has emerged to tackle the so-called "missing heritability" of drug response in
      disease. Research on psychiatric disorders has only recently started to assess
      the link between epigenetic alterations and treatment outcomes. DNA methylation,
      the best characterised epigenetic mechanism to date, is discussed here in the
      context of schizophrenia and antipsychotic treatment outcomes. The majority of
      published studies have assessed the influence of antipsychotics on methylation
      levels in specific neurotransmitter-associated candidate genes or at the genome
      wide level. While these studies illustrate the epigenetic modifications
      associated with antipsychotics, very few have assessed clinical outcomes and the
      potential of differential DNA methylation profiles as predictors of antipsychotic
      response. Results from other psychiatric disorder studies, such as depression and
      bipolar disorder, provide insight into what may be achieved by schizophrenia
      pharmacoepigenomics. Other aspects that should be addressed in future research
      include methodological challenges, such as tissue specificity, and the influence
      of genetic variation on differential methylation patterns.

PMID- 29017765
TI  - Accuracy of shock index versus ABC score to predict need for massive transfusion
      in trauma patients.
AB  - BACKGROUND: Various scoring systems have been developed to predict need for
      massive transfusion in traumatically injured patients. Assessments of Blood
      Consumption (ABC) score and Shock Index (SI) have been shown to be reliable
      predictors for Massive Transfusion Protocol (MTP) activation. However, no study
      has directly compared these two scoring systems to determine which is a better
      predictor for MTP activation. The primary objective was to determine whether ABC
      or SI better predicted the need for MTP in adult trauma patients with severe
      hemorrhage. METHODS: This was a retrospective cohort study which included all
      injured patients who were trauma activations between January 1, 2009 and December
      31, 2013 at an urban Level I trauma center. Patients <18 years old or with
      traumatic brain injury (TBI) were excluded. ABC and SI were calculated for each
      patient. MTP was defined as need for >10 units PRBC transfusion within 24h of
      emergency department arrival. Sensitivity, specificity, and area under the
      receiver operating characteristic curve (AUROC) were used to evaluate scoring
      systems' ability to predict effective MTP utilization. RESULTS: A total of 645
      patients had complete data for analysis. Shock Index >=1 had sensitivity of 67.7%
      (95% CI 49.5%-82.6%) and specificity of 81.3% (95% CI 78.0%-84.3%) for predicting
      MTP, and ABC score >=2 had sensitivity of 47.0% (95% CI 29.8%-64.9%) and
      specificity of 89.8% (95% CI 87.2%-92.1%). AUROC analyses showed SI to be the
      strongest predictor followed by ABC score with AUROC values of 0.83 and 0.74,
      respectively. SI had a significantly greater sensitivity (P=0.035), but a
      significantly weaker specificity (P<0.001) compared to ABC score. CONCLUSION: ABC
      score and Shock Index can both be used to predict need for massive transfusion in
      trauma patients, however SI is more sensitive and requires less technical skill
      than ABC score.

PMID- 29017766
TI  - Survival and health related quality of life after severe trauma - a 15 years
      follow up study.
AB  - INTRODUCTION: As the primary treatment of patients with severe trauma continues
      to improve, increasing interest has been directed towards long-term survival and
      Health Related Quality of Life (HRQoL). In trauma patients, there are few studies
      describing long-term outcome using tools specifically directed at HRQoL.
      HYPOTHESIS: HRQoL measured with EQ-5D is significantly reduced compared to the
      Danish norm score 15 years after severe injury. MATERIALS AND METHODS: All
      patients more than 18 years of age, admitted to a level 1 trauma center from
      March 1996 to September 1997 were prospectively included and scored with Injury
      Severity Score (ISS). Survival status was recorded in May 2012 and EQ-5D
      questionnaires were sent out. RESULTS: 95 of the original 154 trauma patients
      were eligible for participation. The response rate was 66%. The average EQ-5D
      index score in the trauma population was significantly reduced compared to the
      index score in the Danish norm population (P=0.00, one-sample t-test). In
      addition, ISS is associated with HRQoL and ISS>=16 predicts poorer HRQoL.
      CONCLUSION: EQ-5D is significantly reduced 15years after severe trauma High ISS
      was associated with low HRQoL. Knowledge of the distribution and predictors of
      long-term disability can be used to develop more efficient prevention policies
      and to improve trauma care in general.

PMID- 29017767
TI  - Inducible NAD(H)-linked methylglyoxal oxidoreductase regulates cellular
      methylglyoxal and pyruvate through enhanced activities of alcohol dehydrogenase
      and methylglyoxal-oxidizing enzymes in glutathione-depleted Candida albicans.
AB  - BACKGROUND: High methylglyoxal content disrupts cell physiology, but mammals have
      scavengers to prevent glycolytic and mitochondrial dysfunctions. In yeast,
      methylglyoxal accumulation triggers methylglyoxal-oxidizing alcohol dehydrogenase
      (Adh1) activity. While methylglyoxal reductases and glyoxalases have been well
      studied in prokaryotes and eukaryotes, experimental evidence for methylglyoxal
      dehydrogenase (Mgd) and other catalytic activities of this enzyme affecting
      glycolysis and the tricarboxylic acid cycle is lacking. METHODS: A glycine-rich
      cytoplasmic Mgd protein, designated as Mgd1/Grp2, was isolated from glutathione
      depleted Candida albicans. The effects of Mgd1/Grp2 activities on metabolic
      pathophysiology were investigated using knockout and overexpression mutants. We
      measured glutathione-(in)dependent metabolite contents and metabolic effects,
      including viability, oxygen consumption, ADH1 transcripts, and glutathione
      reductase and alpha-ketoglutarate dehydrogenase activities in the mutants. Based
      on the findings, methylglyoxal-oxidizing proteins were monitored to determine
      effects of MGD1/GRP2 disruption on methylglyoxal-scavenging traits during
      glutathione deprivation. RESULTS: Methylglyoxal-oxidizing NAD(H)-linked Mgd1/Grp2
      was found solely in glutathione auxotrophs, and it catalyzed the reduction of
      both methylglyoxal and pyruvate. MGD1/GRP2 disruptants showed growth defects,
      cell-cycle arrest, and methylglyoxal and pyruvate accumulation with mitochondrial
      impairment, regardless of ADH1 compensation. Other methylglyoxal-oxidizing
      enzymes were identified as key glycolytic enzymes with enhanced activity and
      transcription in MGD1/GRP2 disruptants, irrespective of glutathione content.
      CONCLUSIONS: Failure of methylglyoxal and pyruvate dissimilation by Mgd1/Grp2
      deficiency leads to poor glutathione-dependent redox regulation despite
      compensation by Adh1. GENERAL SIGNIFICANCE: This is the first report that
      multifunctional Mgd activities contribute to scavenging methylglyoxal and
      pyruvate to maintain metabolic homeostasis and the redox pool via glycolytic
      enzymes and Adh1 expression.

PMID- 29017768
TI  - Analytical comparison of three different versions of a high-sensitivity cardiac
      troponin I assay over 10years.
AB  - BACKGROUND: Concerns have been raised on the long-term analytical performance of
      high-sensitivity cardiac troponin (hs-cTn) assays with respect to different
      reagent formulations, lots and instrumentation. Our goal for the present study
      was to compare three different versions of an hs-cTnI assay in two different
      study populations to evaluate if assay re-formulation over 10years has also
      affected the analytical results. METHODS: Beckman Coulter's CE marked hs-cTnI
      assay (Access hsTnI, 2017) was tested in 100 lithium heparin plasma samples first
      tested in 2007 with their prototype hs-cTnI assay and in 100 serum samples tested
      with their enhanced hs-cTnI assay in 2011 with comparison performed by Passing
      Bablok regression. The Beckman Coulter hs-cTnI results from 2017 and 2011 from
      the serum samples were also compared to the Abbott ARCHITECT i1000 hs-cTnI
      results (2013) with 3-fold differences used to identify possible outliers.
      Freeze/thaw stability testing (-20 degrees C) was also performed on normal cTnI
      (Beckman=4.0ng/L; Abbott=5.3ng/L) and high cTnI concentration (Beckman=77.6ng/L;
      Abbott=126.1ng/L) lithium heparin plasma pools for both hs-cTnI assays. RESULTS:
      After 3 freeze-thaws the Beckman hs-cTnI assay yielded minor decreases in
      concentrations (normal pool -0.7ng/L and high pool -12.6ng/L lower). Regression
      analyses yielded the following relationship between the Beckman hs-cTnI versions:
      2017 hs-cTnI=2.0*(2007 prototype hs-cTnI)-5.1ng/L and 2017 hs-cTnI=1.04*(2011
      enhanced hs-cTnI)-2.5ng/L. Compared to the Abbott 2013 hs-cTnI results, the 2011
      Beckman enhanced version had 8 results 3-fold higher, with the 2017 Beckman
      version yielding 6 results 3-fold lower. CONCLUSIONS: The 2017 Beckman hs-cTnI
      version (Access hsTnI) is closely aligned with the previous enhanced hs-cTnI
      assay and appears to have reduced the frequency of aberrantly high results.

PMID- 29017769
TI  - Modified kernel principal component analysis using double-weighted local outlier
      factor and its application to nonlinear process monitoring.
AB  - Traditional kernel principal component analysis (KPCA) based nonlinear process
      monitoring method may not perform well because its Gaussian distribution
      assumption is often violated in the real industrial processes. To overcome this
      deficiency, this paper proposes a modified KPCA method based on double-weighted
      local outlier factor (DWLOF-KPCA). In order to avoid the assumption of specific
      data distribution, local outlier factor (LOF) is introduced to construct two LOF
      based monitoring statistics, which are used to substitute for the traditional T2
      and SPE statistics, respectively. To provide better online monitoring
      performance, a double-weighted LOF method is further designed, which assigns the
      weights for each component to highlight the key components with significant fault
      information, and uses the moving window to weight the historical statistics for
      reducing the drastic fluctuations in the monitoring results. Finally, simulations
      on a numerical example and the Tennessee Eastman (TE) benchmark process are used
      to demonstrate the superiority of the proposed DWLOF-KPCA method.

PMID- 29017770
TI  - Longitudinal analysis of serum interleukin-18 in patients with familial
      Mediterranean fever carrying MEFV mutations in exon 10.
AB  - BACKGROUND: Familial Mediterranean fever (FMF) is an autoinflammatory disease
      caused by mutations in the MEFV gene. Mutations in exon 10 are associated with
      typical FMF phenotypes, and patients with exon 10 mutations have higher serum
      levels of interleukin (IL)-18 both during attacks and afebrile phases, compared
      to those without exon 10 mutations. However, longitudinal changes of serum IL-18
      in FMF have not been fully characterized. METHODS: We serially evaluated serum
      levels of pro-inflammatory cytokines, including IL-18, in 12 patients with FMF
      carrying exon 10 mutations, all of whom showed typical FMF attacks. RESULTS:
      Markedly high concentrations of IL-18 were observed in all patients at diagnosis
      (5099+/-6084pg/mL). Serum IL-18 levels declined progressively after colchicine
      treatment in 7 patients (group A), whereas 5 patients showed continued elevation
      of circulating IL-18, despite declines in IL-6 and neopterin (group B). The mean
      follow-up times in the two groups were 4.7+/-3.2 and 4.8+/-1.5 years,
      respectively. The mean serum IL-18 level at the last hospital visit in group B
      was 4190+/-2610 pg/mL. There were no differences in onset age, initial IL-18
      levels, and colchicine doses between the groups. FMF attacks almost disappeared
      in both groups, but there were trends towards more frequent subtle symptoms such
      as abdominal discomfort in group B. CONCLUSIONS: Sustained elevation of serum IL
      18 may suggest the presence of persistent subclinical inflammation. Therefore,
      longitudinal examination of serum IL-18 may contribute to better follow-up of FMF
      patients with exon 10 mutations.

PMID- 29017771
TI  - Association of interleukin 13 gene polymorphisms and plasma IL 13 level with risk
      of systemic lupus erythematosus.
AB  - Interleukin (IL) 13 plays a critical role in inflammatory diseases, including
      systemic lupus erythematosus (SLE). This study aims to explore the potential
      association of IL-13 polymorphisms with the risk of SLE. We genotyped IL-13
      rs20541, rs848 and rs1295686 using Snapshot SNP genotyping assays. Plasma IL-13
      level was determined by enzyme-linked immunosorbent assay (ELISA). We found that
      rs20541 was associated with increased risk of SLE (CT vs. CC: adjusted OR=1.43,
      95%CI, 1.04-1.99, P=.030; TT vs. CC: adjusted OR=1.73, 95%CI, 1.10-2.73, P=.018;
      CT/TT vs. CC: adjusted OR=1.50, 95%CI, 1.10-2.04, P=.010; T vs. C adjusted
      OR=1.34, 95%CI, 1.08-1.93, P=.031). CT and TT genotypes in rs20541 were
      associated with increased risk of renal disorder in SLE (CT vs. CC: adjusted
      OR=1.97, 95%CI, 1.18-3.28, P=.009; TT vs. CC: adjusted OR=2.42, 95%CI, 1.22-4.77,
      P=.011). Moreover, The concentration of IL-13 was significantly elevated in
      rs20541 CT/TT genotypes compared with CC genotype (P<.001). These results suggest
      that rs20541 CT/TT genotypes may be a risk factor for SLE, probably by increasing
      the level of IL-13.

PMID- 29017772
TI  - T cell activation Rho GTPase activating protein (TAGAP) is upregulated in
      clinical and experimental arthritis.
AB  - Genome-wide association studies have identified various susceptibility variants
      and loci associated with incidence of rheumatoid arthritis (RA) in different
      populations. One of these is T cell activation Rho GTPase activating protein
      (TAGAP). The present study sought to measure the expression of TAGAP in RA
      patients, CD4+ T cells subsets from healthy humans and in mice with collagen
      induced arthritis. Peripheral blood mononuclear cells (PBMC) from RA patients and
      tissues of arthritic mice at different stages of the disease were used for the
      evaluation of TAGAP mRNA expression. Increased TAGAP expression was observed in
      RA patients compared to healthy controls, and there were differences in the
      expression level of TAGAP in the tissues of mice with experimental arthritis.
      Gene expression in CD4+ T cells from healthy humans was greatest 4 h after
      activation and protein expression was greatest after 24 h. The expression of
      TAGAP was not correlated with CD4+ lymphocyte subsets which were enriched for
      functionally defined subsets (Th17, Treg, Th1), further indicating its utility as
      an indicator of lymphocyte activation. These findings indicate that increased
      TAGAP expression is a distinguishing feature of inflammatory disease and further
      highlight the role of TAGAP in RA susceptibility.

PMID- 29017773
TI  - TLR11 or TLR12 silencing reduces Leishmania major infection.
AB  - Toll-like receptors (TLRs) recognize the pathogen-associated molecular patterns
      (PAMPs) and induce host-protective immune response. The role of the profilin
      recognizing TLR11/TLR12 in Leishmania infection is unknown. Herein, we report
      that TLR11/ TLR12 expression increases in virulent L. major-infected macrophages
      but is prevented by miltefosine, an anti-leishmanial drug. While lipohosphoglycan
      (LPG) increases, LPG or TLR2 blockade prevents, the heightened TLR11/TLR12
      expression. LPG-TLR2 interaction triggers MyD88- and TIRAP-mediated signaling
      enhancing ERK-1/2 activation and increased production of IL-10 that promotes
      TLR11/TLR12 expression. Profilin expression was higher in the virulent L. major
      and L. donovani parasites than that observed in the avirulent parasites. TLR11 or
      TLR12 silencing reduces parasite burden and increases IFN-gamma, but reduces IL
      4, production indicating that TLR11 and TLR12 play a pro-leishmanial role.

PMID- 29017775
TI  - SID Resident Retreat Increases Retention in Academic Practice.

PMID- 29017774
TI  - An alternative biomarker-based approach for the prediction of proteins known to
      sensitize the respiratory tract.
AB  - Many natural and industrial proteins are known to have properties that can result
      in type I hypersensitivity, however, to date, no validated test system exists
      that can predict the sensitizing potential of these allergens. Thus, the
      objective of this study was to develop a protocol based on the myeloid cell-based
      Genomic Allergen Rapid Detection (GARD) assay that can be used to assess and
      predict the capacity of protein allergens known to induce sensitization in the
      respiratory tract. Cellular responses induced by eight selected proteins were
      assessed using transcriptional profiling, flow cytometry and multiplex cytokine
      analysis. 391 potential biomarkers were identified as a predictive signature and
      a series of cross-validations supported the validity of the model. These results
      together with biological pathway analysis of the transcriptomic data indicate
      that the investigated cell system is able to capture relevant events linked to
      type I hypersensitization.

PMID- 29017776
TI  - Early outcomes of percutaneous pulmonary valve implantation using the Edwards
      SAPIEN XT transcatheter heart valve system.
AB  - BACKGROUND: Patients with congenital or acquired heart defects affecting the
      pulmonary valve and right ventricular outflow tract (RVOT) commonly require
      multiple surgical interventions, resulting in significant morbidity. A less
      invasive alternative is percutaneous pulmonary valve implantation (PPVI). Though
      studies have previously reported the safety and efficacy of the early generation
      transcatheter heart valves (THVs), data on more recent devices are severely
      lacking. METHODS AND RESULTS: We performed a multinational, multicentre,
      retrospective, observational registry analysis of patients who underwent PPVI
      using the Edwards SAPIEN XT THV. Of the 46 patients that were enrolled, the
      majority had tetralogy of Fallot as the underlying diagnosis (58.7%), and
      stentless xenograft as the most common RVOT anatomy (34.8%). Procedural success
      rate was high (93.5%), with a low frequency of periprocedural complications and
      adverse events (6.5% and 10.9%, respectively). At 30days post-procedure, NYHA
      class had improved significantly (90.6% were at NYHA I or II). The rate of
      moderate/severe pulmonary regurgitation had decreased from 76.1% at baseline to
      5.0% at 30days, and the calculated peak systolic gradient had decreased from 45.2
      (SD+/-21.3) mmHg to 16.4 (SD+/-8.0) mmHg, with these values remaining low up to
      2years. CONCLUSIONS: The data suggest the efficacy and safety of the SAPIEN XT
      THV in PPVI in common anatomies in patients with conduits, as well as those with
      native pulmonary valves or transannular patches. Continued data collection is
      necessary to verify long-term findings. CLINICALTRIALS. GOV IDENTIFIER:
      NCT02302131.

PMID- 29017777
TI  - Predictive value of inter-atrial block for new onset or recurrent atrial
      fibrillation: A systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Inter-atrial block (IAB) is characterized by a delay
      of inter-atrial conduction and is defined electrocardiographically by a P-wave
      duration (PWD)>120ms. Several studies have implicated IAB in the development of
      new onset atrial fibrillation (AF), whereas others have reported no significant
      associations. Moreover, there has been no systematic evaluation of the predictive
      value of IAB in AF recurrence. Therefore, we conducted a systematic review and
      meta-analysis to examine whether IAB predicts new onset AF or AF recurrence.
      METHODS: PubMed and Embase databases were searched through 30th July 2017 for
      studies investigating the relationship between IAB and AF. RESULTS: The initial
      search identified 260 studies, of which 16 studies met the inclusion criteria.
      This meta-analysis included 18,204 patients (mean age 56+/-13, 48% male) with a
      mean follow-up period of 15.1years. IAB significantly predicted new onset AF
      (hazard ratio [HR]: 2.42, 95% confidence interval [CI]: 1.44 to 4.07, P=0.001;
      84%). For partial IAB, the risk of new onset AF did not reach statistical
      significance (HR: 1.42, 95% CI: 0.85 to 2.34; P=0.18; I2=13%). Contrastingly,
      advanced IAB was a significant predictor of new onset AF with a pooled HR of 2.58
      (95% CI: 1.35 to 4.96; P<0.01; I2=67%). IAB also predicted AF recurrence after
      ablation (HR: 2.59, 95% CI: 1.35 to 4.96; P<0.01; I2=67%). CONCLUSIONS: IAB is a
      significant predictor of both new onset AF and AF recurrence.

PMID- 29017778
TI  - Patent Ductus Arteriosus closure in preterms less than 2kg: Surgery versus
      transcatheter.
AB  - BACKGROUND: As new devices come into the market, percutaneous techniques improve
      and interventionalists become more experienced; percutaneous closure gets more
      common in preterms. In this study we aimed to compare efficacy and safety of
      Patent Ductus Arteriosus closure surgically versus transcatheter method in
      preterms <2kg. Best of our knowledge this study is the first one that compares
      outcomes of surgery and percutaneous Patent Ductus Arteriosus closure in
      preterms. METHODS & RESULTS: Between the dates July 1997 to October 2014 in our
      center Patent Ductus Arteriosus of 26 patients <2kg were closed percutaneously
      (Group A) and 31 less than 2kg operated (Group B). Weight of patients in
      percutaneous Patent Ductus Arteriosus closure group was significantly more than
      the surgery group. Mean gestational age of the patients in Group A was 30+/
      1.8weeks, in group B was 28.6+/-3.5weeks. In group A; all cases were closed
      successfully except 4 cases: device embolization in 2, cardiac tamponade and
      iatrogenic aortic coarctation were seen. Pneumomediastinum and chylothorax were
      the major complications of the surgery group. There was no statistically
      significance between complication and success rates between two groups.
      CONCLUSION: Percutaneous Patent Ductus Arteriosus closure is the candidate for
      taking the place of surgery in preterms. However, it is not applied routinely;
      can only be done in fully equipped large centers by experienced
      interventionalists.

PMID- 29017779
TI  - Targeted inhibition of hantavirus replication and intracranial pathogenesis by a
      chimeric protein-delivered siRNA.
AB  - Hantavirus (HV) infection, which underlies hantavirus hemorrhagic fever with
      renal syndrome and hantavirus pulmonary syndrome, remains to be a severe clinical
      challenge. Here, we synthesized small interfering RNAs (siRNAs) that target the
      encoding sequences of HV strain 76-118, and validated their inhibitory role in
      virus replication in HV-infected monkey kidney Vero E6 cells. A chimeric protein,
      3G1-Ckappa-tP, consisting of a single-chain antibody fragment (3G1) against the
      HV surface envelop glycoprotein, the constant region of human immunoglobulin
      kappa chain (Ckappa), and truncated protamine (amino acids 8-29, tP), was further
      generated. The fusion protein showed high affinity to HV antigen on the infected
      cell membrane, and internalized through clathrin-mediated endocytosis; it bound
      to siRNAs via the basic nucleic acid-rich protamine fragment, leading to their
      specific delivery into HV-infected cells and efficient inhibition of virus
      replication. An encephalitis mouse model was established via intracranial HV
      administration. Intraperitoneal injection of siRNAs complexed with 3G1-Ckappa-tP
      achieved specific distribution of siRNAs in HV-infected brain cells,
      significantly reduced HV antigen levels, and effective protection from HV
      infection-derived animal death. These results provide a compelling rationale for
      novel therapeutic protocols designed for HV infection and related disorders.

PMID- 29017781
TI  - Long-term effects of sport concussion on cognitive and motor performance: A
      review.
AB  - Motor and cognitive dysfunction is intractable sequela in the acute stage of
      concussion. While typical concussion recovery occurs in two weeks, empirical
      evidence suggests that some sequela persist beyond this period, though there is
      inconsistency surrounding the duration the sequela persist. In part, confusion
      around the issue is limited by the volume of literature evaluating those with a
      concussion history, permitting vast interpretations of significance. The purpose
      of this paper is to review the concussion history literature, summarizing the
      long-term effects of concussion history on motor and cognitive performance.
      Additionally, this review intends to provide direction and options of future
      investigations addressing the long-term effects of concussion on motor and
      cognitive performance.

PMID- 29017780
TI  - Using theta and alpha band power to assess cognitive workload in multitasking
      environments.
AB  - Cognitive workload is of central importance in the fields of human factors and
      ergonomics. A reliable measurement of cognitive workload could allow for
      improvements in human machine interface designs and increase safety in several
      domains. At present, numerous studies have used electroencephalography (EEG) to
      assess cognitive workload, reporting the rise in cognitive workload to be
      associated with increases in theta band power and decreases in alpha band power.
      However, results have been inconsistent with some failing to reach the required
      level of significance. We hypothesized that the lack of consistency could be
      related to individual differences in task performance and/or to the small sample
      sizes in most EEG studies. In the present study we used EEG to assess the
      increase in cognitive workload occurring in a multitasking environment while
      taking into account differences in performance. Twenty participants completed a
      task commonly used in airline pilot recruitment, which included an increasing
      number of concurrent sub-tasks to be processed from one to four. Subjective
      ratings, performances scores, pupil size and EEG signals were recorded. Results
      showed that increases in EEG alpha and theta band power reflected increases in
      the involvement of cognitive resources for the completion of one to three
      subtasks in a multitasking environment. These values reached a ceiling when
      performances dropped. Consistent differences in levels of alpha and theta band
      power were associated to levels of task performance: highest performance was
      related to lowest band power.

PMID- 29017782
TI  - Eyes have ears: Indexing the orienting response to sound using pupillometry.
AB  - The rare occurrence of a sound deviating from the auditory background tends to
      trigger attentional orienting. While some sympathetic physiological responses can
      be used to index this orienting response, findings surrounding the pupillary
      dilation response (PDR) as a proxy for the orienting response are conflicting.
      The current study was tailor-designed to examine whether the PDR satisfies
      specific criteria of an orienting response index, namely the classic habituation
      pattern and a sensitivity to the size of the deviation. The PDR decrement to a
      repeated standard sound, recovery to a deviant sound, and dishabituation to the
      re-presentation of the standard were assessed for small and large deviations
      embedded in irrelevant auditory sequences. The PDR not only showed habituation
      and dishabituation, but also recovered in correspondence with the magnitude of
      the acoustic deviation. This consistency between variations of the PDR and
      orienting response's properties indicates that the PDR is a valid index of the
      auditory orienting response.

PMID- 29017783
TI  - Design and examination of potent pseudosubstrate-based oligonucleotide inhibitors
      against bacterial topoisomerase IV.
AB  - Topoisomerase IV is an enzyme that is mainly responsible for unwinding
      interlocked DNA strands at the final stage of prokaryotic DNA replication. Due to
      its exclusivity in prokaryotes, topoisomerase IV has been identified as a
      validated target for quinolone-based antibiotics in the past years for treating
      bacterial infection. In consideration that bacterial resistance to such
      antibiotics has occurred constantly, several newly designed pseudosubstrate
      oligonucleotides as DNA topoisomerase IV inhibitors have been examined during our
      recent investigations. Among them, the nick-, gap- and mismatched base pair
      containing oligonucleotides displayed significantly high inhibitory effects
      toward topoisomerase IV. It is our anticipation that the outcomes of our current
      studies could be beneficial for the future development of pseudosubstrate-based
      enzyme inhibitors as well as new types of antibiotics.

PMID- 29017784
TI  - Arginine-rich cross-linking peptides with different SV40 nuclear localization
      signal content as vectors for intranuclear DNA delivery.
AB  - The major barriers for intracellular DNA transportation by cationic polymers are
      their toxicity, poor endosomal escape and inefficient nuclear uptake. Therefore,
      we designed novel modular peptide-based carriers modified with SV40 nuclear
      localization signal (NLS). Core peptide consists of arginine, histidine and
      cysteine residues for DNA condensation, endosomal escape promotion and
      interpeptide cross-linking, respectively. We investigated three polyplexes with
      different NLS content (10 mol%, 50 mol% and 90 mol% of SV40 NLS) as vectors for
      intranuclear DNA delivery. All carriers tested were able to condense DNA, to
      protect it from DNAase I and were not toxic to the cells. We observed that cell
      cycle arrest by hydroxyurea did not affect transfection efficacy of NLS-modified
      carriers which we confirmed using quantitative confocal microscopy analysis.
      Overall, peptide carrier modified with 90 mol% of SV40 NLS provided efficient
      transfection and nuclear uptake in non-dividing cells. Thus, incorporation of NLS
      into arginine-rich cross-linking peptides is an adequate approach to the
      development of efficient intranuclear gene delivery vehicles.

PMID- 29017785
TI  - Carborane-linked 2'-deoxyuridine 5'-O-triphosphate as building block for
      polymerase synthesis of carborane-modified DNA.
AB  - 5-[(p-Carborane-2-yl)ethynyl]-2'-deoxyuridine 5'-O-triphosphate was synthesized
      and used as a good substrate in enzymatic construction of carborane-modified DNA
      or oligonucleotides containing up to 21 carborane moieties in primer extension
      reactions by DNA polymerases.

PMID- 29017786
TI  - Identification of novel PI3K inhibitors through a scaffold hopping strategy.
AB  - A scaffold hopping strategy, including intellectual property availability
      assessment, was successfully applied for the discovery of novel PI3K inhibitors.
      Compounds were designed based on the chemical structure of the lead compound ETP
      46321, a potent PI3K inhibitor, previously reported by our group. The new
      generated compounds showed good in vitro potency and selectivity, proved to
      inhibit potently the phosphorylation of AKTSer473 in cells and demonstrated to be
      orally bioavailable, thus becoming potential back-up candidates for ETP-46321.

PMID- 29017787
TI  - Dual antioxidant structures with potent anti-inflammatory, hypolipidemic and
      cytoprotective properties.
AB  - Novel amide derivatives of trolox, 3,5-di-tert-butyl-4-hydroxybenzoic acid, (E)-3
      (3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid and cinnamic acid with cysteamine
      and l-cysteine ethyl ester were synthesised. In four cases, the disulfide
      derivatives were also isolated and tested. All compounds were examined for
      antioxidant activity, expressed as their ability to inhibit lipid peroxidation
      and to scavenge free radicals. They were found to demonstrate up to 17-fold
      better activity than that of the parent antioxidant acids. They could reduce
      acute inflammation up to 87%. The most active antioxidant compounds were further
      tested for their in vivo hypolipidemic effect, which ranged from 47% to 73%, and
      for their ability to protect the liver against oxidative toxicity caused by high
      paracetamol dose. The disulfide derivatives of 3,5-di-tert-butyl-4-hydroxybenzoic
      acid and cinnamic acid had no antioxidant activity and presented equal or lower
      anti-inflammatory effect than their thiol analogues, indicating that their
      molecular characteristics may not permit biological barrier penetration.

PMID- 29017789
TI  - "You're right, you're right, I know you're right".

PMID- 29017788
TI  - Zaluzanin C (ZC) induces osteoblast differentiation through regulating of
      osteogenic genes expressions in early stage of differentiation.
AB  - Zaluzanin C (ZC) is a sesquiterpene lactones used in herbal medicines. This study
      examined the effects of ZC on osteoblast differentiation. ZC-induced mRNA
      expressions levels of osteogenic genes in C3H10T1/2 and MC3T3-E1 cells were
      determined by RT-PCR and qPCR. ZC regulated the expression of key osteogenic
      genes in the early stage of differentiation, including distal-less homeobox 5
      (Dlx5), DNA-binding protein inhibitor (Id1) and Runt-related transcription factor
      2 (Runx2). In addition, ZC increased Runx2 promoter activity, as assessed via a
      luciferase assay, and Runx2 protein level. These results suggest that ZC may
      enhance osteoblast differentiation by upregulating the expression of osteogenic
      genes, especially early stage like as Dlx5, Id1 and Runx2.

PMID- 29017790
TI  - Why do some conduits get infected and others don't?

PMID- 29017791
TI  - Preoperative thoracic false lumen branches are predictors of aortic enlargement
      after stent grafting for DeBakey IIIb aortic dissection.
AB  - OBJECTIVE: The study objective was to assess the effect of preoperative thoracic
      false lumen branches on thoracic aortic enlargement along the stent graft after
      thoracic endovascular aortic repair for DeBakey IIIb aortic dissection. METHODS:
      From January 2011 to December 2013, 67 patients who underwent thoracic
      endovascular aortic repair for DeBakey IIIb aortic dissection were
      retrospectively investigated. We assessed preoperative thoracic false lumen
      branches and diameter measurements at the level of the tracheal carina. Patients
      with a median follow-up of 12.2 months (interquartile range, 4.3-26.6 months)
      were categorized into 2 groups based on a receiver operating characteristic curve
      analysis: group A (preoperative thoracic false lumen branches >=8, n = 28) and
      group B (preoperative thoracic false lumen branches <8, n = 39). Diameter changes
      over time were evaluated using a mixed model approach. A multivariate Cox
      regression analysis was used to study the influence of the preoperative thoracic
      false lumen branches on thoracic aortic enlargement along the stent graft.
      RESULTS: Six patients experienced thoracic aortic enlargement along the stent
      graft during follow-up (6 in group A, 0 in group B). The cumulative thoracic
      aortic enlargement along the stent-graft rate was higher in group A than in group
      B (log-rank P < .01). Diameter data showed significantly more reduction of the
      thoracic false lumen from preprocedure to 12 months in group B than in group A
      (change difference, 2.51; standard error, 0.99; P = .01). Complete false lumen
      thrombosis was more prominent in group B than in group A at each follow-up time
      point. After multivariate adjustment, preoperative thoracic false lumen branches
      were associated with thoracic aortic enlargement along the stent graft (hazard
      ratio, 2.92; 95% confidence interval, 1.06-8.01). CONCLUSIONS: Preoperative
      thoracic false lumen branches are a morphologic predictor of thoracic aortic
      enlargement along the stent graft in DeBakey IIIb aortic dissection after
      thoracic endovascular aortic repair.

PMID- 29017793
TI  - Coming soon to an operating theater near you.

PMID- 29017792
TI  - Three-dimensional printing of navigational template in localization of pulmonary
      nodule: A pilot study.
AB  - BACKGROUND: Small pulmonary nodules are a common problem, especially with the
      wide implementation of lung cancer-screening program. This poses a great
      challenge to thoracic surgeons because of the difficulty of nodule localization.
      We recently built an efficient, customized navigational template using 3
      dimensional (3D) printing technology to facilitate the procedure of lung nodule
      localization. This study aims to investigate its feasibility in clinical
      application. METHODS: Patients with peripheral lung nodules (<2 cm) were
      enrolled. Preadmission computed tomography images were downloaded and
      reconstructed into a 3D model. A digital model of the navigational template was
      designed via computer-aided design software and then exported into 3D printer to
      produce physical template. The precision of the template-guided nodule
      localization and associated complications were evaluated. RESULTS: A total of 16
      patients were enrolled, and 18 nodules were localized through template-guided
      localization. The success rate of lung nodule localization was 100%, and the
      median time of localization was 13 minutes (range 10-16 minutes). In our series,
      no significant complication occurred, except for 2 asymptomatic pneumothoraxes.
      The median deviation between the localizer and the center of the nodule was 10.0
      mm, ranging from 5 to 20 mm. CONCLUSIONS: This novel navigational template
      created by 3D printing technology is feasible, and it has acceptable accuracy for
      the application in lung nodule localization. The use of this navigational
      template could facilitate the procedure of lung nodule localization and may
      potentially break the dependence of percutaneous localization on computed
      tomography scanning.

PMID- 29017794
TI  - Size matters: Indexed left atrial size predicts late survival after aortic valve
      replacement.

PMID- 29017795
TI  - Long-term effects of sleep deprivation on neuronal activity in four hypothalamic
      areas.
AB  - Lack of adequate sleep has become increasingly common in our 24/7 society.
      Unfortunately diminished sleep has significant health consequences including
      metabolic and cardiovascular disease and mental disorders including depression.
      The pathways by which reduced sleep adversely affects physiology and behavior are
      unknown. We found that 6h of sleep deprivation in adult male rats induces changes
      in neuronal activity in the lateral hypothalamus, the paraventricular nucleus,
      the arcuate nucleus and the mammillary bodies. Surprisingly, these alterations
      last for up to 48h. The data show that sleep loss has prolonged effects on the
      activity of multiple hypothalamic areas. Our data indicate also that measuring
      electroencephalographic slow wave activity underestimates the amount of time that
      the hypothalamus requires to recover from episodes of sleep deprivation. We
      propose that these hypothalamic changes underlie the well-established
      relationship between sleep loss and several diseases such as metabolic disorders,
      stress and depression and that sufficient sleep is vital for autonomic functions
      controlled by the hypothalamus.

PMID- 29017796
TI  - Anti-inflammatory effect of collagen tripeptide in atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin
      disease in which type 2 allergic inflammation plays an important role. Collagen
      tripeptide (CTP) is a functional collagen fraction with a high content of Gly-X-Y
      tripeptides. OBJECTIVE: To examine the effect of CTP on inflammation in AD.
      METHODS: Levels of inflammatory cytokines and chemokines, such as thymus- and
      activation-regulated chemokine (TARC), macrophage-derived chemokine, and thymic
      stromal lymphopoietin (TSLP), were examined in human keratinocytes supplemented
      with or without CTP under AD-like inflammation. To evaluate the functional effect
      of CTP, a migration assay was performed using the supernatants of cultured
      keratinocytes treated with CTP. The signaling pathway for CTP inhibitory activity
      was also determined. Additionally, we conducted a clinical trial with seventeen
      AD patients who were assigned randomly to receive daily for 12 weeks either 3.9g
      of a CTP product or normal collagen peptides (CP). The eruption area, severity
      scoring of atopic dermatitis (SCORAD), skin hydration, transepidermal water loss
      (TEWL), and itching score were evaluated. The levels of TARC, serum IgE, lactate
      dehydrogenase, and eosinophil counts at week 12 were also compared with those at
      the start of administration. RESULTS: In human keratinocytes, TARC and TSLP mRNA
      and protein levels were inhibited significantly by CTP treatment under AD-like
      inflammation. Supernatants obtained from CTP-treated keratinocytes inhibited cell
      migration. STAT1 phosphorylation was significantly decreased by CTP in a dose
      dependent manner. In the clinical trial, 13 patients (7 for CTP, 6 for CP)
      completed the study. The eruption area, SCORAD, and TEWL at week 12 were reduced
      significantly compared with the initial values in the CTP but not CP group. A
      significant reduction in the serum TARC level was observed only in the CTP group
      at week 12. Other blood parameters were not improved in either group. CONCLUSION:
      CTP may have therapeutic benefit for AD by inhibiting type 2-skewed allergic
      inflammation.

PMID- 29017797
TI  - Palmoplantar keratoderma in Slurp1/Slurp2 double-knockout mice.

PMID- 29017798
TI  - Recombinant anticoccidial vaccines - a cup half full?
AB  - Eimeria species parasites can cause the disease coccidiosis, most notably in
      chickens. The occurrence of coccidiosis is currently controlled through a
      combination of good husbandry, chemoprophylaxis and/or live parasite vaccination;
      however, scalable, cost-effective subunit or recombinant vaccines are required.
      Many antigens have been proposed for use in novel anticoccidial vaccines,
      supported by the capacity to reduce disease severity or parasite replication,
      increase body weight gain in the face of challenge or improve feed conversion
      under experimental conditions, but none has reached commercial development.
      Nonetheless, the protection against challenge induced by some antigens has been
      within the lower range described for the ionophores against susceptible isolates
      or current live vaccines prior to oocyst recycling. With such levels of efficacy
      it may be that combinations of anticoccidial antigens already described are
      sufficient for development as novel multi-valent vaccines, pending identification
      of optimal delivery systems. Selection of the best antigens to be included in
      such vaccines can be informed by knowledge defining the natural occurrence of
      specific antigenic diversity, with relevance to the risk of immediate vaccine
      breakthrough, and the rate at which parasite genomes can evolve new diversity.
      For Eimeria, such data are now becoming available for antigens such as apical
      membrane antigen 1 (AMA1) and immune mapped protein 1 (IMP1) and more are
      anticipated as high-capacity, high-throughput sequencing technologies become
      increasingly accessible.

PMID- 29017799
TI  - Automated segmentation of abdominal subcutaneous adipose tissue and visceral
      adipose tissue in obese adolescent in MRI.
AB  - PURPOSE: To develop a reliable and reproducible automatic technique to segment
      and measure SAT and VAT based on MRI. MATERIALS AND METHODS: Chemical-shift water
      fat MRI were taken on twelve obese adolescents (mean age: 16.1+/-0.6, BMI: 31.3+/
      2.3) recruited under the health monitoring program. The segmentation applied a
      spoke template created using Midpoint Circle algorithm followed by Bresenham's
      Line algorithm to detect narrow connecting regions between subcutaneous and
      visceral adipose tissues. Upon satisfaction of given constrains, a cut was
      performed to separate SAT and VAT. Bone marrow was consisted in pelvis and femur.
      By using the intensity difference in T2*, a mask was created to extract bone
      marrow adipose tissue (MAT) from VAT. Validation was performed using a semi
      automatic method. Pearson coefficient, Bland-Altman plot and intra-class
      coefficient (ICC) were applied to measure accuracy and reproducibility. RESULTS:
      Pearson coefficient indicated that results from the proposed method achieved high
      correlation with the semi-automatic method. Bland-Altman plot and ICC showed good
      agreement between the two methods. Lowest ICC was obtained in VAT segmentation at
      lower regions of the abdomen while the rests were all above 0.80. ICC (0.98-0.99)
      also indicated the proposed method performed good reproducibility. CONCLUSION: No
      user interaction was required during execution of the algorithm and the segmented
      images and volume results were given as output. This technique utilized the
      feature in the regions connecting subcutaneous and visceral fat and T2* intensity
      difference in bone marrow to achieve volumetric measurement of various types of
      adipose tissue in abdominal site.

PMID- 29017800
TI  - Plasticity of the epigenome during early-life stress.
AB  - Early life adversity remains a significant risk factor for the development of a
      host of negative behavioural and pathological outcomes in adulthood long after
      the stressor is over. Recent evidence indicates that these lasting effects of ELS
      may occur via alterations in the epigenetic landscape. Here, we review the main
      findings of the effects of early life adversity on DNA methylation, histone post
      translational modification, and non-coding RNAs in the context of psychiatric
      disease in animal models and human cohorts. We specifically explore how early
      life adversity alters epigenetic patterns in both a global manner, and in
      specific candidate genes that play a role in relevant systems such as the
      hypothalamic-pituitary-adrenal axis, as well as neurotransmitter and
      neuroendocrine signalling. We also discuss how individual factors, such as
      genetics, sex, and age, as well as the type, and timing of early life adversity,
      can create differential susceptibility and significantly moderate outcomes.
      Although challenges remain in deciphering the complexity of how the early
      environment interacts with individual factors to determine epigenetic patterns,
      as well as how to translate these mechanistic findings into clinically relevant
      populations, the reviewed literature sheds light on the potential of the field to
      identify effective interventions for vulnerable individuals.

PMID- 29017801
TI  - Influence of Increased Posterior Tibial Slope in Total Knee Arthroplasty on Knee
      Joint Biomechanics: A Computational Simulation Study.
AB  - BACKGROUND: The reconstructed posterior tibial slope (PTS) plays a significant
      role in restoring knee kinematics in cruciate-retaining-total knee arthroplasty
      (TKA). A few studies have reported the effect of the PTS on biomechanics.
      METHODS: This study investigates the effect of the PTS on tibiofemoral (TF)
      kinematics, patellofemoral (PF) contact stress, and forces at the quadriceps,
      posterior cruciate ligament (PCL) and collateral ligament after cruciate
      retaining-TKA using computer simulations. The simulation for the validated TKA
      finite element model was performed under deep knee bend condition. All analyses
      were repeated from -3 degrees  to 15 degrees  PTS in increments of 3 degrees .
      RESULTS: The kinematics on the TF joint translated increasingly posteriorly when
      the PTS increased. Medial and lateral contact points translated in posterior
      direction in extension and flexion as PTS increased. The maximum contact stress
      on the PF joint and quadriceps, and collateral ligament force decreased when the
      PTS increased. An implantation of the tibial plate with increased PTS reduced the
      PCL load. Physiologic insert movement led to an increasingly posterior position
      of the femur and reduced quadriceps force especially for knee flexion angles
      above high flexion (120 degrees ) when compared to TKA with a decreased slope of
      the tibial base plate. CONCLUSION: An increase in the PTS increased medial and
      lateral movements without paradoxical motion. However, an excessive PTS indicated
      progressive loosening of the TF joint gap due to a reduction in collateral
      ligament tension during flexion.

PMID- 29017802
TI  - Big Data and Total Hip Arthroplasty: How Do Large Databases Compare?
AB  - BACKGROUND: Use of large databases for orthopedic research has become extremely
      popular in recent years. Each database varies in the methods used to capture data
      and the population it represents. The purpose of this study was to evaluate how
      these databases differed in reported demographics, comorbidities, and
      postoperative complications for primary total hip arthroplasty (THA) patients.
      METHODS: Primary THA patients were identified within National Surgical Quality
      Improvement Programs (NSQIP), Nationwide Inpatient Sample (NIS), Medicare
      Standard Analytic Files (MED), and Humana administrative claims database (HAC).
      NSQIP definitions for comorbidities and complications were matched to
      corresponding International Classification of Diseases, 9th Revision/Current
      Procedural Terminology codes to query the other databases. Demographics,
      comorbidities, and postoperative complications were compared. RESULTS: The number
      of patients from each database was 22,644 in HAC, 371,715 in MED, 188,779 in NIS,
      and 27,818 in NSQIP. Age and gender distribution were clinically similar.
      Overall, there was variation in prevalence of comorbidities and rates of
      postoperative complications between databases. As an example, NSQIP had more than
      twice the obesity than NIS. HAC and MED had more than 2 times the diabetics than
      NSQIP. Rates of deep infection and stroke 30 days after THA had more than 2-fold
      difference between all databases. CONCLUSION: Among databases commonly used in
      orthopedic research, there is considerable variation in complication rates
      following THA depending upon the database used for analysis. It is important to
      consider these differences when critically evaluating database research.
      Additionally, with the advent of bundled payments, these differences must be
      considered in risk adjustment models.

PMID- 29017803
TI  - Increasing Perioperative Communication With Automated Mobile Phone Messaging in
      Total Joint Arthroplasty.
AB  - BACKGROUND: Automated mobile phone messaging has not been reported in total joint
      arthroplasty (TJA). Our purpose was to compare Press Ganey (PG) and Hospital
      Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores between
      TJA patients who did and did not receive perioperative automated mobile phone
      messages. METHODS: Patients were prospectively enrolled and received messages for
      1 week prior until 2 weeks after TJA. Message content included reminders,
      activity, and pain control. Patients answered select PG/HCAHPS and questions
      regarding their experience with the automated communication platform. Average
      PG/HCAHPS scores were compared to historical TJA patients in the 3-year window
      prior (control group) with significance P < .05. RESULTS: Thirty-seven
      consecutive patients were approached and 92% (n = 34) were enrolled. The
      experimental group was 47% male, with 80% patients between 51 and 75 years. The
      experimental (n = 30) and control groups (n = 26) were similar. Patients
      receiving messages were more likely to have a good understanding of health
      responsibilities (P = .024) and feel that the care team demonstrated shared
      decision-making (P = .024). Of patients enrolled, 87% felt messages helped them
      be more prepared for surgery, 100% felt messages kept them better informed, and
      97% would participate again. CONCLUSION: TJA patients who received perioperative
      communication via automated mobile phone messaging had improved patient
      satisfaction scores postoperatively. Patients perceived this form of
      communication was useful and kept them better informed. Automated mobile phone
      messaging can be an easily integrated, helpful adjunct to surgeons, healthcare
      systems, and case managers to more effectively communicate with patients
      undergoing TJA in this era of value-based care.

PMID- 29017804
TI  - Nanomanufacturing through microfluidic-assisted nanoprecipitation: Advanced
      analytics and structure-activity relationships.
AB  - We have employed microfluidics (cross-shaped chip) for the preparation of drug
      loaded poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles. The polymer
      precipitates from an acetone solution upon its controlled laminar mixing (flow
      focusing) with an aqueous solution of a surfactant, allowing for an operator
      independent, up-scalable and reproducible preparative process of
      nanoformulations. Firstly, using PEGylated surfactants we have compared batch and
      microfluidic processes, and showed the superior reproducibility of the latter and
      its strong dependency on the acetone/water ratio (flow rate ratio). We have then
      focused on the issue of purification from free surfactant, and employed advanced
      characterization techniques such as flow-through dynamic light scattering as the
      in-line quality control technique, and field flow fractionation (FFF) with
      dynamic and static light scattering detection, which allowed the detection of
      surfactant micelles in mixture with nanoparticles (hardly possible with stand
      alone dynamic light scattering). Finally, we have shown that the choice of
      polymer and surfactant affects the release behaviour of a model drug
      (paclitaxel), with high molecular weight PLGA (RG756) and low molecular weight
      surfactant (tocopheryl poly(ethylene glycol) 1000 succinate, TPGS) apparently
      showing higher burst and accelerated release.

PMID- 29017805
TI  - Atherosclerotic plaque characteristics are not associated with future
      cardiovascular events in patients undergoing iliofemoral endarterectomy.
AB  - BACKGROUND: Plaque characteristics such as intraplaque hemorrhage (IPH) have been
      associated with secondary cardiovascular events (CVE) in patients undergoing
      carotid endarterectomy. In addition, carotid plaques containing macrophage
      infiltration or a large lipid core size were associated with less restenosis. It
      is currently unknown whether iliofemoral plaque histopathologic characteristics
      are predictive for secondary CVE in patients with peripheral arterial disease
      undergoing iliofemoral endarterectomy. The aim of this study was to examine the
      association between iliofemoral atherosclerotic plaque characteristics and
      secondary CVE in patients undergoing iliofemoral endarterectomy. METHODS: There
      were 497 patients with iliofemoral atherosclerotic disease who underwent primary
      endarterectomy of the iliac or femoral artery from 2002 to 2013 included. All
      specimen were uptaken in the Athero Express biobank and 7 histologic plaque
      characteristics were analyzed: calcification, collagen, fat content, IPH,
      macrophages, smooth muscle cells, and vessel density. The composite CVE consisted
      of myocardial infarction, cerebrovascular accident, peripheral (re
      )interventions, and cardiovascular death. Multivariate Cox regression models were
      used to examine the association between plaque and the composite end point during
      a follow-up period of 3 years. RESULTS: Of the 497 patients, 225 (46.4%)
      experienced a composite CVE within 3 years after the initial surgery. Calcified
      plaques were univariably associated with composite CVE (hazard ratio [HR], 1.32;
      95% confidence interval [CI], 1.00-1.73; P = .049). After correction for
      confounders, multivariable analyses showed no association between calcified
      plaques and composite CVE (HR, 1.13; 95% CI, 0.85-1.50; P = .413). IPH was not
      predictive of secondary CVE (HR, 1.02; 95% CI, 0.79-1.33; P = .867). CONCLUSIONS:
      In this cohort of patients with peripheral arterial disease undergoing
      iliofemoral endarterectomy, investigated atherosclerotic plaque characteristics
      were not independently associated with secondary CVE during follow-up.

PMID- 29017806
TI  - Implementation of a bundled protocol significantly reduces risk of spinal cord
      ischemia after branched or fenestrated endovascular aortic repair.
AB  - OBJECTIVE: Spinal cord ischemia (SCI) is a devastating complication after
      branched or fenestrated endovascular aortic repair (B/FEVAR) for thoracoabdominal
      aortic disease. The purpose of this analysis was to describe the impact of a
      bundled clinical care protocol designed to reduce the risk of SCI in this
      population of patients. METHODS: A bundled SCI prevention protocol including
      cerebrospinal fluid drainage, blood pressure parameters, transfusion goals, and
      pharmacologic adjuncts (steroids, naloxone) was initiated in May 2015. Before
      that date, portions of the protocol (cerebrospinal fluid drainage in particular)
      were used in an informal fashion in patients perceived to be at high risk.
      B/FEVAR cases completed from January 2012 to May 2016 were reviewed, and outcomes
      before (n = 223) and after (n = 70) SCI bundle application were compared. The
      primary end point was the incidence of SCI events. Secondary end points included
      length of stay, complications, and survival. High-risk patients for SCI were
      defined as those undergoing B/FEVAR resulting in aortic coverage equivalent to
      open Crawford extent I to III thoracoabdominal aortic aneurysm (TAAA) repair.
      Survival was estimated using Kaplan-Meier life-table analysis. RESULTS:
      Postprotocol patients were more likely to be older (75 +/- 7 vs 72 +/- 8 years; P
      = .03), to have an American Society of Anesthesiologists class 4 designation (94%
      vs 81%; P = .04), and to be treated for TAAA (67% vs 56%; P = .004). Postprotocol
      pre-emptive spinal drain use was greater in high-risk patients (100% vs 87%; P =
      .04) but significantly decreased in lower risk patients (suprarenal aneurysm or
      extent IV TAAA: 5% after protocol implementation vs 21% before protocol
      implementation; P = .04). Rates of any SCI before and after implementation of the
      bundled protocol were 13% (n = 29 of 223) and 3% (n = 2 of 70; P = .007),
      respectively. In comparing high-risk patients, protocol use resulted in an even
      more significant reduction in SCI rate (19% [28 of 144] vs 4% [2 of 50]; P =
      .004). Postoperative morbidity (41% vs 33%; P = .2) and 30-day mortality (5% vs
      1%; P = .3) were not different between groups. However, patients treated on
      protocol had significantly improved 1-year survival (99% +/- 1% after protocol
      implementation vs 90% +/- 2% before protocol implementation; log-rank, P = .05).
      CONCLUSIONS: Implementation of a bundled multimodal protocol may significantly
      reduce risk of SCI after B/FEVAR, with the greatest risk reduction occurring in
      the most vulnerable patients. Interestingly, reduction in SCI risk was associated
      with improvement in 1-year survival.

PMID- 29017807
TI  - Unplanned 30-day readmission in patients with diabetic foot wounds treated in a
      multidisciplinary setting.
AB  - OBJECTIVE: Readmission rates are known to be high for vascular surgery patients
      in general, but there are limited data describing the risk of surgical and
      nonsurgical readmission among patients with diabetic foot ulcers (DFUs). Our aim
      was to identify factors associated with unplanned readmission in DFU patients
      treated in a multidisciplinary setting. METHODS: We studied a single-center
      cohort of patients enrolled in a multidisciplinary diabetic foot service (July
      2012-June 2017). Readmissions were stratified by planned vs unplanned and related
      vs unrelated to the wound and vascular status. Predictors of unplanned 30-day
      readmission were examined with univariable and multivariable logistic regression
      models including all covariates with P <= .10. RESULTS: There were 460 admissions
      in 206 patients during the study period, including 99 total readmissions (21.5%).
      Readmissions were categorized as planned (n = 18 [18.2%]) or unplanned (n = 81
      [81.8%]) and as related (n = 67 [67.7%]) or unrelated (n = 32 [32.3%]) to the
      wound and vascular status. The most frequent reasons for unplanned 30-day
      readmission were deterioration of the foot wound (41%), vascular complications
      (15%), gastrointestinal complications (10%), cardiac complications (8%), and
      acute kidney injury (8%). The average length of stay for the initial admission
      was 9.0 +/- 7.1 days, whereas the average unplanned readmission length of stay
      was 8.6 +/- 9.1 days (P = .38). On univariable analysis, hypertension (odds ratio
      [OR], 2.80; 95% confidence interval [CI], 1.19-6.59), peripheral arterial disease
      (OR, 1.80; 95% CI, 1.09-2.99), and exposure to an open vascular operation (OR,
      2.64; 95% CI, 1.34-5.17) were associated with a higher risk of 30-day unplanned
      readmission (P <= .02). Private, military, or self-pay insurance was protective
      (OR, 0.52; 95% CI, 0.28-0.97). Wound duration, location, and Wound, Ischemia, and
      foot Infection (WIfI) classification were not associated with readmission (P >=
      .22). After risk adjustment, only hypertension (OR, 2.80; 95% CI, 1.19-6.59) and
      current smoking (OR, 1.95; 95% CI, 1.02-3.73) were independently associated with
      30-day unplanned readmission, but the predictive accuracy of the model was weak
      (C statistic = 0.69). CONCLUSIONS: We found a 17% unplanned 30-day readmission
      rate in this prospective cohort of DFU patients enrolled in a multidisciplinary
      diabetic foot service. Only current smoking and hypertension were independent
      predictors of readmission after risk adjustment. These findings suggest that
      implementation of a smoking cessation program may be beneficial to reduce
      unplanned readmissions in DFU patients. They also highlight the complexity
      involved in achieving comprehensive DFU care and the unpredictability of
      readmissions in this unique population of patients.

PMID- 29017809
TI  - Discussion.

PMID- 29017808
TI  - A novel technique for duplex-guided office-based interventions for patients with
      acute arteriovenous fistula occlusion.
AB  - OBJECTIVE: The purpose of the study was to aggressively salvage acutely occluded
      arteriovenous fistulas (AVFs) using duplex imaging as the sole imaging modality
      for percutaneous transluminal angioplasty of acutely thrombosed AVF. METHODS:
      Over a period of 12 months, 14 patients with acute thrombosis of their AVFs
      underwent 18 procedures in a single center for AVF salvage. All 14 patients
      presented with chronic renal failure, and six were diabetic. All patients were
      treated under duplex guidance alone. Treatment included simple balloon dilation
      and maceration (group A; n =10 procedures [56%]) for subacute thrombosis or
      pharmacomechanical thrombectomy (group B; n = 8 procedures [44%]) for more
      hypoechoic thrombus. A successful procedure was defined as immediate restoration
      of flow through the AVF. RESULTS: Of the 18 procedures, 13 (72%) were successful.
      Of the 14 patients, thrombus was located at the perianastomotic AVF in 6 (43%),
      proximal-mid AVF in 6 (43%), mid AVF in 1 (7%), and distal AVF in 1 (7%). From
      group A, six (60%) were successful. From group B, seven (88%) were successful.
      Among the unsuccessful procedures, one group B patient was hypercoagulable
      (polycythemia vera). Of the 18 procedures, 16 (89%) were treated within 2 weeks
      from when duplex revealed the presence of thrombus. Early rethrombosis (<1-month
      patency) occurred in three cases (17%), and these patients received new fistulas.
      Full restoration of the fistula flow was established in 14 cases (78%). Of these
      14 patients, 8 (57%) are currently on hemodialysis via fistula, 3 patients (21%)
      had newly placed fistulas after failed interventions, 2 patients (14%) are not on
      dialysis yet, and 1 patient (7%) with polycythemia vera disorder is on dialysis
      via a Tesio catheter (MedComp, Harleysville, Pa). CONCLUSIONS: The sole use of
      duplex ultrasound imaging to salvage acutely occluded AVFs using percutaneous
      transluminal angioplasty is a safe and effective alternative to traditional
      treatment of thrombosed failing/maturing AVF.

PMID- 29017811
TI  - A randomized trial comparing three Delphi feedback strategies found no evidence
      of a difference in a setting with high initial agreement.
AB  - OBJECTIVES: The objective of the study was to explore the impact of different
      feedback strategies on (1) subsequent agreement and (2) variability in Delphi
      studies. STUDY DESIGN AND SETTING: A two-round Delphi survey, with a list of
      outcomes generated from the results of a systematic review and interviews, was
      undertaken while developing a core outcomes set for prostate cancer including two
      stakeholder groups (health professionals and patients). Seventy-nine outcomes
      were scored on a scale of one (not important) to nine (critically important).
      Participants were randomized in round 2 to receive round 1 feedback from peers
      only, multiple stakeholders separately, or multiple stakeholders combined.
      RESULTS: Agreement on outcomes retained for all feedback groups was high (peer:
      92%, multiple separate: 90%, multiple combined: 84%). There were no statistically
      significant reduction in variability for peer vs. multiple separate (0.016 [
      0.035, 0.067]; P = 0.529), or multiple separate vs. multiple combined feedback
      (0.063 [-0.003, 0.129]; P = 0.062). Peer feedback statistically significantly
      reduced variability compared with multiple combined feedback (0.079 [0.001,
      0.157]; P = 0.046). CONCLUSIONS: We found no evidence of a difference between
      different feedback strategies in terms of the number of outcomes retained or
      reduction in variability of opinion. However, this may be explained by the high
      level of existing agreement in round 1. Further methodological studies nested
      within Delphi surveys will help clarify the best strategy.

PMID- 29017810
TI  - Redox-mediated regulation of connexin proteins; focus on nitric oxide.
AB  - Connexins are membrane proteins that form hemichannels and gap junction channels
      at the plasma membrane. Through these channels connexins participate in autocrine
      and paracrine intercellular communication. Connexin-based channels are tightly
      regulated by membrane potential, phosphorylation, pH, redox potential, and
      divalent cations, among others, and the imbalance of this regulation have been
      linked to many acquired and genetic diseases. Concerning the redox potential
      regulation, the nitric oxide (NO) has been described as a modulator of the
      hemichannels and gap junction channels properties. However, how NO regulates
      these channels is not well understood. In this mini-review, we summarize the
      current knowledge about the effects of redox potential focused in NO on the
      trafficking, formation and functional properties of hemichannels and gap junction
      channels.

PMID- 29017812
TI  - Anaerobic dynamic membrane bioreactor (AnDMBR) for wastewater treatment: A
      review.
AB  - Recently, an increasing level of attention has focused on the emerging technology
      of anaerobic dynamic membrane bioreactors (AnDMBRs), owing to its merits such as
      low membrane module cost, easy control of membrane fouling, low energy
      consumption and sludge production, as well as biogas production. As research on
      AnDMBRs is still in the nascent stage, an introduction of bioreactor
      configurations, dynamic membrane (DM) module, and DM layer formation and cleaning
      is firstly presented. The process performance of the AnDMBR for wastewater
      treatment is then reviewed with regard to pollutant removal, DM filterability,
      biogas production, and potential advantages over the conventional anaerobic
      membrane bioreactor (AnMBR). In addition, the important parameters affecting
      process performance are briefly discussed. Lastly, the challenges encountered and
      perspectives regarding the future development of the AnDMBR process to promote
      its practical applications are presented.

PMID- 29017813
TI  - Plasmid DNA purification by zirconia magnetic nanocomposite.
AB  - A zirconia magnetic nanocomposite was prepared by a co-precipitation method in
      one step. The synthesized nanocomposite was characterized by scanning electron
      microscopy, energy-dispersive X-ray and Fourier transform infrared spectroscopy.
      The nanocomposite was applied for the adsorption/desorption of tobacco plant DNA
      (as a model). Experimental parameters controlling adsorption efficiency,
      including pH of binding solution, extraction time, the amount of nanocomposite
      and ionic strength, were optimized. To obtain high desorption efficiency, the
      effects of pH, the ionic strength of elution buffer and desorption time were
      investigated. The nanocomposite provided the adsorption capacity of 53.5 mg g-1
      for DNA. The adsorption and desorption efficiency of the sorbent was found to be
      greater than 98 and 81%, respectively. The zirconia magnetic nanocomposite was
      used for the purification of plasmid DNA (pDNA) from Escherichia coli cell
      culture. The yield and purity of pDNA obtained by the method were compared to
      those obtained by the phenol-chloroform solvent extraction and a commercial kit.

PMID- 29017815
TI  - RNA polymerase II pausing and transcriptional regulation of the HSP70 expression.
AB  - Heat-shock proteins (HSPs) belong to the chaperone protein family whose
      expression is induced by different stresses including heat-shock. In response to
      the extracellular or intrinsic stimuli and stresses, HSPs play important roles in
      the maintenance of cellular homeostasis. HSP70, a major HSP protein (molecular
      weight, 70 KDa), regulates diverse cellular pathways including protein quality
      control, translation, immune response, and cancer survival. As a critical
      cellular defense system to minimize damages from cellular stresses, HSP70
      expression and transcriptional activation are rapidly regulated, mainly through
      the action of a transcription activator, Heat shock factor 1 (HSF1). Eukaryotic
      HSP70 genes are well-characterized; they utilize a transcriptional mechanism
      termed as RNA polymerase II (Pol II) promoter-proximal pausing. Pol II promoter
      proximal pausing enables synchronized gene expression in a number of mammalian
      protein-coding and non-protein coding genes upon the reception of gene activating
      signals. In particular, Drosophila and human HSP70 genes serve as a bona fide
      model system to understand the mechanisms of Pol II pausing and pause release. In
      this review, we will discuss HSP70 transcription and the newly discovered
      mechanisms that regulate HSP70 gene expression.

PMID- 29017814
TI  - Pituitary adenylate cyclase activating polypeptide induces long-term,
      transcription-dependent plasticity and remodeling at autonomic synapses.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional
      neuropeptide, widely expressed in the nervous system (Vaudry et al., 2009; Starr
      and Margiotta, 2016). At neuronal synapses where transmission is mediated by
      nicotinic acetylcholine receptors (nAChRs) transient PACAP exposure increases the
      frequency and amplitude (FS and AS) of spontaneous excitatory postsynaptic
      currents (sEPSCs) within minutes. This short-term (ST) plasticity requires high
      affinity PACAP receptor (PAC1R) signaling via adenylate cyclase (AC), cyclic AMP
      (cAMP), Protein kinase A (PKA) and obligatory nAChR-dependent stimulation of
      nitric oxide (NO) synthesis to retrogradely increase presynaptic ACh release
      (Pugh et al., 2010; Jayakar et al., 2014). Remarkably, synaptic changes persist
      48h after transient PACAP exposure, featuring a similar increase in FS and an
      even larger increase in AS. Pharmacological studies reveal that this long-term
      (LT) plasticity requires PACAP/PAC1R signaling via AC and cAMP, but unlike ST
      plasticity, Phospholipase-C and new gene transcription are also necessary,
      whereas PKA, nAChR, impulse and NO synthase (NOS1) activities are dispensable. In
      accord with the increases in FS and AS characterizing LT plasticity, miniature
      EPSC (mEPSC) frequency, ACh release (quantal content), and mEPSC amplitude
      (quantal size) all increased in parallel. Consistent with these functional
      changes, imaging studies reveal that LT, but not ST, PACAP-induced plasticity is
      accompanied by increases in presynaptic terminal size, postsynaptic nAChR cluster
      size and density, and the size and density of co-localized pre- and post-synpatic
      sites. Thus PACAP/PAC1R signaling induces mechanistically distinct forms of
      synaptic plasticity, with a ST form arising from acute, membrane-delimited
      processes, and a LT form arising from transcription-dependent alterations in the
      function and structural arrangement of pre- and post-synaptic components.

PMID- 29017816
TI  - Oral and dermal diflubenzuron exposure causes a hypothalamic-pituitary-thyroid
      (HPT) axis disturbance in the Mongolian racerunner (Eremias argus).
AB  - Diflubenzuron (DFB) is a potential endocrine-disrupting chemical. However, its
      thyroid endocrine effect on reptiles has not been reported. In this study,
      immature lizards (Eremias argus) were exposed to 20 mg kg-1 DFB once a week for
      42 days through oral or dermal routes. Their body weight, plasma thyroid hormone
      levels, thyroid gland histology and the transcription of hypothalamic-pituitary
      thyroid (HPT) axis-related genes in different tissues were assessed to explore
      the effects of DFB on the HPT axis of lizards. The body weight decreased
      significantly only after the dermal exposure to DFB. Triiodothyronine (T3) to
      thyroxine (T4) ratio in the male plasma also significantly increased after the
      dermal exposure. After oral exposure, the activity of thyroid gland was
      positively related to the thyroid hormone levels. Furthermore, the alterations in
      thyroid hormone levels affected the HPT axis-related gene expression, which was
      tissue dependent and sexually selected. The thyroid hormone receptor genes
      (tralpha and trbeta) in the brain and thyroid were more sensitive to oral
      exposure. However, only the dermal treatment affected the tralpha, trbeta and
      type 2 deiodinase (dio2) genes in the male liver. These results suggest that DFB
      exposure caused sex-specific changes in the thyroid function of lizards, and the
      dermal treatment may be an important route for the risk assessment of reptiles.

PMID- 29017817
TI  - Classification of beta-hairpin repeat proteins.
AB  - In recent years, a number of new protein structures that possess tandem repeats
      have emerged. Many of these proteins are comprised of tandem arrays of beta
      hairpins. Today, the amount and variety of the data on these beta-hairpin repeat
      (BHR) structures have reached a level that requires detailed analysis and further
      classification. In this paper, we classified the BHR proteins, compared
      structures, sequences of repeat motifs, functions and distribution across the
      major taxonomic kingdoms of life and within organisms. As a result, we identified
      six different BHR folds in tandem repeat proteins of Class III (elongated
      structures) and one BHR fold (up-and-down beta-barrel) in Class IV ("closed"
      structures). Our survey reveals the high incidence of the BHR proteins among
      bacteria and viruses and their possible relationship to the structures of amyloid
      fibrils. It indicates that BHR folds will be an attractive target for future
      structural studies, especially in the context of age-related amyloidosis and
      emerging infectious diseases. This work allowed us to update the RepeatsDB
      database, which contains annotated tandem repeat protein structures and to
      construct sequence profiles based on BHR structural alignments.

PMID- 29017819
TI  - Jasmonates are signals in the biosynthesis of secondary metabolites - Pathways,
      transcription factors and applied aspects - A brief review.
AB  - Jasmonates (JAs) are signals in plant stress responses and development. One of
      the first observed and prominent responses to JAs is the induction of
      biosynthesis of different groups of secondary compounds. Among them are nicotine,
      isoquinolines, glucosinolates, anthocyanins, benzophenanthridine alkaloids,
      artemisinin, and terpenoid indole alkaloids (TIAs), such as vinblastine. This
      brief review describes modes of action of JAs in the biosynthesis of
      anthocyanins, nicotine, TIAs, glucosinolates and artemisinin. After introducing
      JA biosynthesis, the central role of the SCFCOI1-JAZ co-receptor complex in JA
      perception and MYB-type and MYC-type transcription factors is described. Brief
      comments are provided on primary metabolites as precursors of secondary
      compounds. Pathways for the biosynthesis of anthocyanin, nicotine, TIAs,
      glucosinolates and artemisinin are described with an emphasis on JA-dependent
      transcription factors, which activate or repress the expression of essential
      genes encoding enzymes in the biosynthesis of these secondary compounds. Applied
      aspects are discussed using the biotechnological formation of artemisinin as an
      example of JA-induced biosynthesis of secondary compounds in plant cell
      factories.

PMID- 29017818
TI  - Room temperature bioproduction, isolation and anti-microbial properties of stable
      elemental copper nanoparticles.
AB  - In nanoparticle production there are a number of important considerations that
      must be made. Producing nanoparticles of uniform size and shape is vital, but no
      less important is ensuring the production process is as efficient as possible in
      time, cost and energy. Traditional chemical and physical methods of nanoparticle
      production often involve high temperatures and pressures, as well as the use of
      toxic substrates; in contrast the bioproduction of nanoparticles is greener and
      requires a smaller input of energy resources. Here we outline a method for the
      straightforward bioproduction of stable, uniform elemental (zero-valent) copper
      nanoparticles at room temperature, and demonstrate how their size and shape can
      be modified by subsequent pH manipulation. We also highlight a potential
      application for these biogenic copper nanoparticles by demonstrating their
      potential to inhibit bacterial growth.

PMID- 29017820
TI  - Possible Utility of the Basophil Activation Test for the Analysis of Mechanisms
      Involved in Allergic Transfusion Reactions.
AB  - Allergic transfusion reactions (ATRs) are the most common adverse reactions
      occurring during transfusion of blood components. Although most reactions are
      mild and involve cutaneous manifestations, severe ATRs including life-threatening
      anaphylaxis may also occur. The mechanisms of ATRs are largely unknown because
      they have not been well studied. One of the reasons for this may be the absence
      of a standard assay system for investigating these processes. Basophils and/or
      mast cells are key effector cells in immediate-type allergic reactions. They
      possess the unique ability to degranulate upon cross-linking of specific IgE
      bound on the membrane-bound, high-affinity IgE receptor or upon direct
      stimulation by exposure to allergens. Basophils are present in peripheral blood,
      unlike mast cells which are located in tissues. Therefore, basophils are valuable
      for the clinical testing of allergy. Consequently, the basophil activation test
      (BAT) was developed as a simple blood test for the diagnosis of allergic
      reactions to substances such as foods, inhalants, medicines and venom. In the
      last decade, the BAT has also been applied to transfusion medicine; 5 pilot
      studies revealed that the supernatants of the responsible blood products
      activated basophils in the BAT in 13 ATR cases, suggesting a causal relationship
      between ATRs and transfusion. In this review, we describe those cases and explore
      the potential utility of the BAT as a test performed in reference laboratories
      for the analysis of ATRs. We also describe the weaknesses, pitfalls, and
      unanswered issues of this assay.

PMID- 29017822
TI  - Sub-optimal primary surgery leads to unfavorable immunological changes in ovarian
      cancer patients.
AB  - Primary cytoreduction, followed by chemotherapy, is a standard treatment of
      patients with epithelial ovarian cancer (EOC). However, the effectiveness of this
      treatment depend on various elements e.g. type of operation. It is accepted that
      optimal surgery correlates with longer survival of patients. The other element,
      an efficiency of immune system after surgical intervention although important is
      less elucidated. The aim of this study was to establish the impact of optimal and
      sub-optimal operation on immunological status of EOC patients regarding also
      their overall survival (OS). On the day of primary cytoreduction and 7days after,
      the selected serum immunological parameters were determined in 49 patients with
      confirmed EOC. We found that, the level of immunosuppressive (interleukin 10;
      transforming growth factor-beta - TGF-beta1) and pro-inflammatory (interleukin-6
      and 8) cytokines was significantly higher in the group of patients with advanced
      stage of disease, compared to early stage. However, the number of circulating
      CD3+, CD4+ or CD8+ cells, CD19+ and NK cells was similar in both group of EOC
      patients. The overall survival of patients who underwent optimal cytoreduction
      was significantly higher than that in whom only sub-optimal surgery was
      performed. Sub-optimal cytoreduction only partially weakened the serum level of
      TGF-beta1 and IL-8 and what is more enhanced the number of circulating
      CD4+CD25+high cells in patients with advanced stage of disease. Sub-optimal
      surgery and high post-operative level of TGF-beta1 increased the hazard ratio for
      patients. Besides, we noticed that the high pre-operative concentration of TGF
      beta1 could distinguish all EOC patients (independently of FIGO classification)
      for whom optimal or sub-optimal surgery would be applied. Sub-optimal debulking
      resulted in higher immunosuppression and lower OS of EOC patients.

PMID- 29017821
TI  - A novel C3d-containing oligomeric vaccine provides insight into the viability of
      testing human C3d-based vaccines in mice.
AB  - The use of C3d, the final degradation product of complement protein C3, as a
      "natural" adjuvant has been widely examined since the initial documentation of
      its immunogenicity-enhancing properties as a consequence of binding to complement
      receptor 2. Subsequently it was demonstrated that these effects are most evident
      when oligomeric, rather than when monomeric forms of C3d, are linked to various
      test protein antigens. In this study, we examined the feasibility of enhancing
      the adjuvant properties of human C3d further by utilizing C4b-binding protein
      (C4BP) to provide an oligomeric arrayed scaffold fused to the model antigen,
      tetanus toxin C fragment (TTCF). High molecular weight, C3d-containing oligomeric
      vaccines were successfully expressed, purified from mammalian cells and used to
      immunize groups of mice. Surprisingly, anti-TTCF antibody responses measured in
      these mice were poor. Subsequently we established by in vitro and in vivo
      analysis that, in the presence of mouse C3, human C3d does not interact with
      either mouse or even human complement receptor 2. These data confirm the
      requirement to develop murine versions of C3d based adjuvant compounds to test in
      mice or that mice would need to be developed that express both human C3 and human
      CR2 to allow the testing of human C3d based adjuvants in mouse in any capacity.

PMID- 29017823
TI  - Erythroblast differentiation at spleen in Q137E mutant ribosomal protein S19 gene
      knock-in C57BL/6J mice.
AB  - We recently found that erythroblast-like cells derived from human leukaemia K562
      cells express C5a receptor (C5aR) and produce its antagonistic and agonistic
      ligand ribosomal protein S19 (RP S19) polymer, which is cross-linked between K122
      and Q137 by tissue transglutaminases. RP S19 polymer binds to the reciprocal
      C5aRs on erythroblast-like cells and macrophage-like cells derived from human
      monocytic THP-1 cells and promotes differentiation into reticulocyte-like cells
      through enucleation in vitro. To examine the roles of RP S19 polymer in mouse
      erythropoiesis, we prepared Q137E mutant RP S19 gene knock-in C57BL/6J mice. In
      contrast to wild-type mice, erythroblast numbers at the preliminary stage
      (CD71high/TER119low) in spleen based on transferrin receptor (CD71) and
      glycophorin A (TER119) values and erythrocyte numbers in orbital artery bloods
      were not largely changed in knock-in mice. Conversely, erythroblast numbers at
      the early stage (CD71high/TER119high) were significantly decreased in spleen by
      knock-in mice. The reduction of early erythroblast numbers in spleen was enhanced
      by the phenylhydrazine-induced pernicious anemia model knock-in mice and was
      rescued by a functional analogue of RP S19 dimer S-tagged C5a/RP S19. These data
      indicated that RP S19 polymer plays the roles in the early erythroblast
      differentiation of C57BL/6J mouse spleen.

PMID- 29017824
TI  - Early postoperative intraperitoneal chemotherapy is associated with survival
      benefit for appendiceal adenocarcinoma with peritoneal dissemination.
AB  - INTRODUCTION: The combined approach of cytoreductive surgery (CRS) with
      hyperthermic intraperitoneal chemotherapy (HIPEC) has achieved encouraging
      outcomes for patients with PMCA with peritoneal dissemination. However, there is
      little evidence for the use of EPIC in addition to HIPEC in this group of
      patients. PATIENTS AND METHODS: This was a retrospective study of prospectively
      collected data of consecutive patients with PMCA who underwent CRS and
      perioperative intraperitoneal chemotherapy by one surgical team at St George
      Hospital in Sydney, Australia between Jan 1996 and Aug 2016. RESULTS: A total of
      185 patients formed the cohort of this study. However, there was no significant
      difference in terms of hospital mortality (p = 0.632), major morbidity rate (i.e.
      Grade III/IV) (p = 0.444), intensive unit care stay (p = 0.638) and total
      hospital stay (p = 0.0.078). However, patients who received HIPEC and EPIC had a
      significant longer stay in high dependency unit (p < 0.001). Multivariate
      analysis showed combined HIPEC with EPIC is an independent prognostic factor for
      better overall survival (Hazard ratio (HR) = 0.42, 95% confidence interval (CI) =
      0.19-0.92, P = 0.030) and disease free survival (HR = 0.66, 95%CI = 0.44-0.99, p
      = 0.045), adjusted for age, sex, peritoneal cancer index, completeness of
      cytoreduction score, CEA >= 6.5 mg/L, CA19-9 >= 24.0 U/mL and CA125 >= 32.0 U/mL.
      CONCLUSIONS: In summary, the combination of HIPEC and EPIC could potentially
      provide additional survival benefit for patients with PMCA with peritoneal spread
      as compared to HIPEC alone without increasing postoperative morbidity and
      mortality. More studies are warranted to further confirm the potential benefits
      of EPIC in PMCA and address the question of optimal drug and/or duration of EPIC.

PMID- 29017825
TI  - Transcriptomic analysis of Ehrlichia ruminantium during the developmental stages
      in bovine and tick cell culture.
AB  - The use of bioinformatics tools to search for possible vaccine candidates has
      been successful in recent years. In an attempt to search for additional vaccine
      candidates or improve the current heartwater vaccine design, a genome-wide
      transcriptional profile of E. ruminantium (Welgevonden strain) replicating in
      bovine endothelial cells (BA886) and Ixodes scapularis embryonic tick cells
      (IDE8) was performed. The RNA was collected from the infective extracellular
      form, the elementary bodies (EBs) and vegetative intracellular form, reticulate
      bodies (RBs) and was used for transcriptome sequencing. Several genes previously
      implicated with adhesion, attachment and pathogenicity were exclusively up
      regulated in the EBs from bovine and tick cells. Similarly, genes involved in
      adaptation or survival of E. ruminantium in the host cells were up-regulated in
      the RBs from bovine cells. Thus, it was concluded that those genes expressed in
      the EBs might be important for infection of mammalian and tick host cells and
      these may be targets for both cell and humoral mediated immune responses.
      Alternatively, those exclusively expressed in the RBs may be important for
      survival in the host cells. Exported or secreted proteins exclusively expressed
      at this stage are ideal targets for the stimulation of cytotoxic T-lymphocyte
      (CTL) immune responses in the host.

PMID- 29017826
TI  - Disability glare in soft multifocal contact lenses.
AB  - PURPOSE: The study investigated the effect of the design of multifocal contact
      lenses on the sensitivity to contrast and disability glare. METHODS: Contrast
      sensitivity was measured in 16 young adults (mean age: 25.5+/-2.5years) at a
      distance of 2m under two conditions: no-glare and glare. Two designs (Center Near
      and Center Distance) of the Biofinity soft contact lens were used to simulate
      correction for presbyopes, while a correction with single vision trial lenses and
      contact lenses acted as controls. RESULTS: The design of the used multifocal
      contact lenses had a significant influence on the log area under the curve of the
      contrast sensitivity function (AUC-CSF). Compared to the spectacle lens
      correction, the AUC-CSF was significantly reduced, in case CS was measured with
      the Center Near design lens, under the no-glare (p<0.001) and the glare condition
      (p: p<0.001). In case of the Center Distance design contact lens, the AUC-CSF was
      significantly smaller in case CS was tested under glare (p=0.001). Disability
      glare (DG) was depending on the spatial frequency and the design of the
      multifocal lens, while the Center Distance design produced higher amounts of DG
      (p<0.001), compared to the other used corrections. CONCLUSION: The optical design
      of a multifocal contact lenses has a significant impact on the contrast
      sensitivity as well as the disability glare. In order to dispense the best
      correction in terms of contact lenses, the sensitivity to contrast under no-glare
      and glare conditions should be tested a medium spatial frequencies.

PMID- 29017827
TI  - Subjective Global Assessment (SGA) Score Could Be a Predictive Factor for
      Radiation Pneumonitis in Lung Cancer Patients With Normal Pulmonary Function
      Treated by Intensity-Modulated Radiation Therapy and Concurrent Chemotherapy.
AB  - INTRODUCTION: To investigate the relationship between malnutrition and the
      severity of radiation pneumonitis (RP) in patients with lung cancer with normal
      baseline pulmonary function and lungs' V20 < 35% treated by intensity-modulated
      radiation therapy (IMRT) and concurrent chemotherapy. MATERIALS AND METHODS: A
      total of 150 patients with lung cancer who received definitive IMRT (>= 60 Gy)
      and concurrent chemotherapy were enrolled. In the condition of normal baseline
      pulmonary function and strict constraints of the irradiation dose to normal lung
      tissues, we recorded Eastern Cooperative Oncology Group score; concurrent
      chemotherapy; clinical stage; the level of albumin (ALB), hemoglobin, and C
      reactive protein; Subjective Global Assessment (SGA) scores; radiation
      esophagitis grade; V20 of lungs; and mean lung dose. These factors were
      correlated with RP using univariate and multivariate regression analyses.
      RESULTS: Of 150 patients, 12 patients (8.0%) developed Grade 3 to 5 RP, 37
      (24.6%) patients developed grade 3 to 5 esophageal toxicity. In univariate
      analysis, ALB level (P = .002), radiation esophagitis (P < .001), and SGA score
      (P < .001) were significantly associated with RP. Multivariate analysis revealed
      that SGA (P < .001) was the independent predictor of RP. CONCLUSIONS: SGA could
      be a predictor for RP in patients with lung cancer treated with definitive IMRT
      and concurrent chemotherapy.

PMID- 29017829
TI  - Etiology of community-onset monomicrobial bacteremic pneumonia and its clinical
      presentation and outcome: Klebsiella and Pseudomonas matters.
AB  - To describe the difference of the clinical features, bacteremia severity, and
      outcome of patient with community-onset bacteremic pneumonia between Pseudomonas,
      Klebsiella, and other causative microorganisms, the total 278 adults with
      community-onset monomicrobial bacteremic pneumonia were studied in a
      retrospective cohort. Klebsiella (61 patients, 21.9%) and Pseudomonas (22, 7.9%)
      species was the leading and the fifth common pathogen, respectively. More
      patients having initial presentation with critical illness (a Pitt bacteremia
      score >= 4) and a fatal comorbidity (McCabe classification) as well as a higher
      short- (30-day) or long-term (90-day) mortality rate was evidenced in patients
      infected with Klebsiella or Pseudomonas species, compared to other causative
      microorganisms. Compared to patients in the Klebsiella group, more frequencies of
      recent chemotherapy and an initial presentation of febrile neutropenia, and less
      proportions of diabetes mellitus were disclosed among those in the Pseudomonas
      group. Of importance, a significantly differential survival curve between
      Klebsiella or Pseudomonas species and other species during 30-day or 90-day
      period after bacteremia onset but a similarity of Pseudomonas and Klebsiella
      species was evidenced, using the Cox-regression after adjusting the independent
      predictors of 30-day mortality. Conclusively, of pathogens causing community
      onset bacteremic pneumonia, Klebsiella and Pseudomonas species should be
      recognized as the highly virulent pathogens and resulted in poor short- and long
      term prognoses.

PMID- 29017828
TI  - Dissecting the Native Architecture and Dynamics of Cyanobacterial Photosynthetic
      Machinery.
AB  - The structural dynamics and flexibility of cell membranes play fundamental roles
      in the functions of the cells, i.e., signaling, energy transduction, and
      physiological adaptation. The cyanobacterial thylakoid membrane represents a
      model membrane that can conduct both oxygenic photosynthesis and respiration
      simultaneously. In this study, we conducted direct visualization of the global
      organization and mobility of photosynthetic complexes in thylakoid membranes from
      a model cyanobacterium, Synechococcus elongatus PCC 7942, using high-resolution
      atomic force, confocal, and total internal reflection fluorescence microscopy. We
      visualized the native arrangement and dense packing of photosystem I (PSI),
      photosystem II (PSII), and cytochrome (Cyt) b6f within thylakoid membranes at the
      molecular level. Furthermore, we functionally tagged PSI, PSII, Cyt b6f, and ATP
      synthase individually with fluorescent proteins, and revealed the heterogeneous
      distribution of these four photosynthetic complexes and determined their dynamic
      features within the crowding membrane environment using live-cell fluorescence
      imaging. We characterized red light-induced clustering localization and
      adjustable diffusion of photosynthetic complexes in thylakoid membranes,
      representative of the reorganization of photosynthetic apparatus in response to
      environmental changes. Understanding the organization and dynamics of
      photosynthetic membranes is essential for rational design and construction of
      artificial photosynthetic systems to underpin bioenergy development. Knowledge of
      cyanobacterial thylakoid membranes could also be extended to other cell
      membranes, such as chloroplast and mitochondrial membranes.

PMID- 29017831
TI  - Translational therapies for multiple system atrophy: Bottlenecks and future
      directions.
AB  - Over the last decade a prominent amount of studies in preclinical transgenic
      models of multiple system atrophy (MSA) has been performed. These studies have
      helped understand mechanisms downstream to the alpha-synuclein oligodendroglial
      accumulation relevant to human MSA. However, the successful translation of the
      preclinical outcomes into a clinical trial has failed. Looking back, we can now
      identify possible confounders for the failure. Biomarkers of disease progression
      are mostly missing. Early diagnosis and initiation of therapeutic clinical trials
      is limited. The need of both proof-of-concept as well as clinically relevant
      preclinical study designs with clinically relevant timing and preclinical
      readouts is identified as a must in our translational efforts for MSA to date.
      Finally, improved clinical study designs with improved enrollment criteria, and
      measurement outcomes are warranted on the way to finding the successful
      therapeutic approach for MSA. This review provides an overview of experimental
      studies and clinical trials for MSA and the lessons learned over the last decade
      towards the identification of the cure for MSA.

PMID- 29017830
TI  - SUVmax after (18)fluoro-deoxyglucose positron emission tomography/computed
      tomography: A tool to define treatment strategies in pancreatic cancer.
AB  - BACKGROUND: (18)fluoro-deoxyglucose positron emission tomography/computed
      tomography (18FDG-PET/CT) might be a useful tool in the management of pancreatic
      ductal adenocarcinoma (PDAC). AIMS: The aim of this study was to analyze maximum
      standard uptake value (SUVmax) after 18FDG-PET/CT as predictor of survival
      outcomes and method to determine treatment strategies. METHODS: A consecutive
      series of patients who underwent preoperative 18FDG-PET/CT and subsequent
      resection for PDAC were retrospectively reviewed. Patients who underwent
      neoadjuvant chemotherapy were excluded. RESULTS: 46 patients were included in the
      analysis. Median follow-up was 27 months (4-67). Patients who recurred within 12
      months showed a significantly higher preoperative median SUVmax (8.1 vs 6.1,
      p=0.039). Receiver operating characteristics (ROC) curves for disease-free
      survival (DFS) and disease-specific survival (DSS) identified SUVmax of 6.0 as
      optimal cut-off. Multivariate analysis showed that SUVmax >= 6.0 was an
      independent predictor of poor DFS (HR 2.288, p=0.024) and DSS (HR 4.875,
      p<0.001). The combination of SUVmax >=6.0 with CA19.9 >=200U/ml was significantly
      associated with survival outcomes in comparison to patients without concordantly
      elevated values. CONCLUSION: SUVmax >=6.0 is an independent predictor of DFS and
      DSS in resected PDAC. 18FDG-PET/CT might be considered in the preoperative
      evaluation of patients with pancreatic cancer.

PMID- 29017833
TI  - Cross-reactivity in beta-Lactam Allergy.
AB  - beta-Lactam drugs (penicillins, amoxicillin, and cephalosporins) account for
      42.6% of all severe drug-induced anaphylaxis. In this review, we focus on
      clinically significant immunologic cross-reactivity in patients with confirmed
      penicillin allergy to cephalosporins, and the structural involvement of the R1
      and R2 chemical side chains of the cephalosporins causing IgE-mediated cross
      reactivity with penicillin and other cephalosporins. Skin tests predict IgE
      mediated reactions and showed cross-reactivity between penicillins and early
      generation cephalosporins that shared side chains, but confirmatory challenge
      data are lacking. Later-generation cephalosporins, which have distinct side
      chains, do not have any skin test cross-reactivity with penicillin/amoxicillin.
      There is debate as to the involvement of R2 side chains as the antigenic
      determinants that cause IgE-mediated hypersensitivity with various
      cephalosporins. Avoidance of cephalosporins, when they are the drug of choice in
      a penicillin-allergic individual, results in significant morbidity that outweighs
      the low risk of anaphylaxis. We conclude that there is ample evidence to allow
      the safe use of cephalosporins in patients with isolated confirmed penicillin or
      amoxicillin allergy.

PMID- 29017832
TI  - Impact of Rhinitis on Work Productivity: A Systematic Review.
AB  - BACKGROUND: Allergic rhinitis (AR) is increasingly acknowledged as having a
      substantial socioeconomic impact associated with impaired work productivity,
      although available information remains fragmented. OBJECTIVE: This systematic
      review summarizes recently available information to provide a quantitative
      estimate of the burden of AR on work productivity including lost work time (ie,
      absenteeism) and reduced performance while working (ie, presenteeism). METHODS: A
      Medline search retrieved original studies from 2005 to 2015 pertaining to the
      impact of AR on work productivity. A pooled analysis of results was carried out
      with studies reporting data collected through the validated Work Productivity and
      Activity Impairment (WPAI) questionnaire. RESULTS: The search identified 19
      observational surveys and 9 interventional studies. Six studies reported economic
      evaluations. Pooled analysis of WPAI-based studies found an estimated 3.6% (95%
      confidence interval [CI], 2.4; 4.8%) missed work time and 35.9% (95% CI, 29.7;
      42.1%) had impairment in at-work performance due to AR. Economic evaluations
      indicated that indirect costs associated with lost work productivity are the
      principal contributor to the total AR costs and result mainly from impaired
      presenteeism. The severity of AR symptoms was the most consistent disease-related
      factor associated with a greater impact of AR on work productivity, although
      ocular symptoms and sleep disturbances may independently affect work
      productivity. Overall, the pharmacologic treatment of AR showed a beneficial
      effect on work productivity. CONCLUSIONS: This systematic review provides summary
      estimates of the magnitude of work productivity impairment due to AR and
      identifies its main determinant factors. This information may help guide both
      clinicians and health policy makers.

PMID- 29017834
TI  - Validation of an observation tool to assess physical activity-promoting physical
      education lessons in high schools: SOFIT.
AB  - OBJECTIVES: SOFIT+ is an observation tool to measure teacher practices related to
      moderate-to-vigorous physical activity (MVPA) promotion during physical education
      (PE). The objective of the study was to examine the validity of SOFIT+ during
      high school PE lessons. DESIGN: This cross-sectional, observational study tested
      the construct validity of SOFIT+ in boys' and girls' high school PE lessons.
      METHODS: Twenty-one PE lessons were video-recorded and retrospectively coded
      using SOFIT+. Students wore hip-mounted accelerometers during lessons as an
      objective measure of MVPA. Multinomial logistic regression was used to estimate
      the likelihood of students engaging in MVPA during different teacher practices
      represented by observed individual codes and a combined SOFIT+ index-score.
      RESULTS: Fourteen individual SOFIT+ variables demonstrated a statistically
      significant relationship with girls' and boys' MVPA. Observed lesson segments
      identified as high MVPA-promoting were related to an increased likelihood of
      girls engaging in 5-10 (OR=2.86 [95% CI 2.41-3.40]), 15-25 (OR=7.41 [95% CI 6.05
      9.06]), and 30-40 (OR=22.70 [95% CI 16.97-30.37])s of MVPA. For boys, observed
      high-MVPA promoting segments were related to an increased likelihood of engaging
      in 5-10 (OR=1.71 [95% CI 1.45-2.01]), 15-25 (OR=2.69 [95% CI 2.31-3.13]) and 30
      40 (OR=4.26 [95% CI 3.44-5.29])s of MVPA. CONCLUSIONS: Teacher practices during
      high school PE lessons are significantly related to students' participation in
      MVPA. SOFIT+ is a valid and reliable tool to examine relationships between PE
      teacher practices and student MVPA during PE.

PMID- 29017835
TI  - Two goitrogenic 1,3-oxazolidine-2-thione derivatives from Brassicales taxa:
      Challenging identification, occurrence and immunomodulatory effects.
AB  - 1,3-Oxazolidine-2-thione derivatives are glucosinolate-related food constituents
      known to impart (thyreo)toxic properties to some cruciferous vegetables. In this
      work, 5,5-dimethyl-1,3-oxazolidine-2-thione and (-)-(R)-5-phenyl-1,3-oxazolidine
      2-thione, known goitrogens, were isolated from Draba lasiocarpa Rochel
      (Brassicaceae) and Reseda luteola L. (Resedaceae), respectively, and were fully
      spectrally characterized. Subsequently, the occurrence of the two 1,3-oxazolidine
      2-thiones was verified in six additional taxa out of in total 78 screened Serbian
      Brassicales taxa. The stereochemistry of 5-phenyl-1,3-oxazolidine-2-thione was
      inferred from nuclear magnetic resonance experiments with a chiral lanthanide
      shift reagent, employed in this work for the first time for this type of
      compounds. Unexpectedly, during gas chromatography, 5-phenyl-1,3-oxazolidine-2
      thione underwent an unreported thermal core isomerization (1,3-oxazolidine-2
      thione to 1,3-thiazolidine-2-one). These goitrogenic volatile glucosinolate
      products were tested for their effect on rat macrophage viability (three assays)
      and nitric oxide production. It was shown that the compounds displayed different
      levels of cytotoxicity. All tested compounds caused a significant lactate
      dehydrogenase leakage, but only (R)-5-phenyl-1,3-oxazolidine-2-thione
      statistically significantly reduced macrophage mitochondrial activity, whereas
      the racemic 5-phenyl-1,3-oxazolidine-2-thione and 5,5-dimethyl-1,3-oxazolidine-2
      thione had little or no effect. Again only (R)-5-phenyl-1,3-oxazolidine-2-thione
      exerted nitric oxide production-inhibiting properties, suggesting the higher
      immunomodulatory potential of this enantiomer compared with its antipode and
      racemic mixture.

PMID- 29017837
TI  - Robo Ig4 Is a Dimerization Domain.
AB  - Robo receptors play pivotal roles in axonal guidance as well as in neurogenesis,
      angiogenesis, cell migration, and cancer progression and invasiveness. They are
      considered to be attractive drug targets for the treatment of cancer, ocular
      neovascular disorders, chronic kidney diseases, and more. Despite their great
      importance, the mechanisms by which Robo receptors switch from their "off" to
      "on" states remain obscure. One possibility involves a monomer-to-dimer or dimer
      to-monomer transition that facilitates the recruitment and activation of
      enzymatic effectors to instigate intracellular signaling. However, it is not
      known which domains mediate Robo dimerization, or the structural properties of
      the dimeric interactions. Here, we identify the extracellular Ig4 (D4) as a Robo
      dimerization domain. We have determined the crystal structure of the tandem Ig4-5
      domains (D4-5) of human Robo2 and found that a hydrophobic surface on D4 mediates
      close homotypic contacts with a reciprocal D4. Analytical ultracentrifugation
      measurements of intact and mutated D4-5 shows that dimerization through the D4
      interface is specific and has a dimerization dissociation constant of 16.9MUM in
      solution. Direct fluorescence resonance energy transfer dimerization measurements
      in HEK293 cells corroborate the dimerization of transmembrane hRobo2 through D4,
      and a functional COS-7 cell collapse assay links D4-mediated dimerization with
      Robo intracellular signaling. The high level of conservation in the D4
      dimerization interface throughout all Robo orthologs and paralogs implies that D4
      mediated dimerization is a central hallmark in Robo activation and signaling.

PMID- 29017836
TI  - Emerging Insights into Noncanonical Inflammasome Recognition of Microbes.
AB  - Inflammasomes are cytosolic multi-molecular complexes that sense intracellular
      microbial danger signals and metabolic perturbations. Inflammasome activation
      leads to the activation of caspase-1 and the release of pro-inflammatory
      cytokines IL-1beta and IL-18 accompanied by cell death. An inflammasome-based
      surveillance machinery for Gram-negative bacterial infections has been recently
      discovered. This noncanonical inflammasome relies on sensing the cytosolic
      presence of lipopolysaccharide of Gram-negative bacteria via inflammatory
      caspases such as caspase-4, -5, and -11. This review discusses the recent
      findings related to the mechanism of activation of the noncanonical inflammasome
      and its biological functions.

PMID- 29017838
TI  - Diurnal rhythms in peripheral blood immune cell numbers of domestic pigs.
AB  - Diurnal rhythms within the immune system are considered important for immune
      competence. Until now, they were mostly studied in humans and rodents. However,
      as the domestic pig is regarded as suitable animal model and due to its
      importance in agriculture, this study aimed to characterize diurnal rhythmicity
      in porcine circulating leukocyte numbers. Eighteen pigs were studied over periods
      of up to 50 h. Cosinor analyses revealed diurnal rhythms in cell numbers of most
      investigated immune cell populations in blood. Whereas T cell, dendritic cell,
      and eosinophil counts peaked during nighttime, NK cell and neutrophil counts
      peaked during daytime. Relative amplitudes of cell numbers in blood differed in T
      helper cell subtypes with distinctive differentiation states. Mixed model
      analyses revealed that plasma cortisol concentration was negatively associated
      with cell numbers of most leukocyte types, except for NK cells and neutrophils.
      The observed rhythms mainly resemble those found in humans and rodents.

PMID- 29017840
TI  - Focal Atrichia: A Diagnostic Clue in Female Pattern Hair Loss.
AB  - BACKGROUND: Focal atrichia is a common clinical finding in female pattern hair
      loss whose specificity and histologic findings need further clarification.
      OBJECTIVE: To determine the frequency of focal atrichia in various types of hair
      loss and its histologic characteristics in female pattern hair loss. METHODS:
      Part 1: Review of 250 consecutive female patients seen with hair loss for the
      presence of focal atrichia and Part 2: paired biopsies of haired areas vs focal
      atrichia in 18 subjects with female pattern hair loss RESULTS: Focal atrichia was
      seen in 46/104 (44%) of women with female pattern hair loss, including 67% of
      late onset vs 15% of early onset, compared to 3/146 (2%) of those with other hair
      disorders Biopsy findings of focal atrichia in female pattern hair loss showed
      primarily a more progressive miniaturization process than that of haired areas of
      the scalp. LIMITATIONS: Some women with female pattern hair loss may have had
      concomitant chronic telogen effluvium CONCLUSIONS: When present, focal atrichia
      is a clinical clue to the diagnosis of female pattern hair loss, particularly
      late onset subtype.

PMID- 29017839
TI  - Prolongation of rate-corrected QT interval during phenol-croton oil peels.

PMID- 29017841
TI  - Alternating histopathologic pattern in blaschkoid dermatoses with epidermal
      changes: A retrospective series of 61 cases.

PMID- 29017842
TI  - The Frisbee maneuver: A novel method to abort acute attacks of the Raynaud
      phenomenon.

PMID- 29017843
TI  - Short-term reasons for withdrawal and adverse events associated with apremilast
      therapy for psoriasis in real-world practice compared with in clinical trials: A
      multicenter retrospective study.

PMID- 29017844
TI  - Buccinator myomucosal flap for the treatment of velopharyngeal insufficiency in
      patients with cleft palate and/or lip.
AB  - INTRODUCTION: The interpretation of the speech results obtained with the
      buccinator myomucosal flap in the treatment of velopharyngeal insufficiency in
      patients with cleft palate has been limited by the restriction in the number of
      patients and the time of postoperative follow-up. OBJECTIVE: To evaluate the
      effect of the buccinator myomucosal flap on speech hypernasality in the treatment
      of patients with cleft palate and velopharyngeal insufficiency. METHODS: Patients
      with repaired cleft palate (+/- lip) who were submitted to surgical correction of
      velopharyngeal insufficiency using the bilateral buccinator myomucosal flap were
      assessed. Hypernasality (scores 0 [absent], 1 [mild], 2 [moderate], or 3
      [severe]) was analyzed by three evaluators by measuring the audiovisual records
      collected in early and late preoperative and postoperative periods (3 and 12
      months, respectively). The values were considered significant for a 95%
      Confidence Interval (p<0.05). RESULTS: Thirty-seven patients with cleft palate
      (+/- lip) showing moderate (16.2%) or severe (83.8%) hypernasality in the
      preoperative period were included. Analyses of the late postoperative period
      showed that hypernasality (0.5+/-0.7) was significantly (p<0.05) lower than the
      hypernasality of the preoperative and recent postoperative periods (2.8+/-0.4 and
      1.7+/-0.9, respectively). CONCLUSION: The buccinator myomucosal flap is effective
      in reducing/eliminating hypernasality in patients with cleft palate (+/- lip) and
      velopharyngeal insufficiency.

PMID- 29017845
TI  - The relationship between dentine hypersensitivity, dietary acid intake and
      erosive tooth wear.
AB  - OBJECTIVES: To assess the interplay between dietary acid intake, toothbrushing
      and erosive tooth wear as aetiological factors in self-reported DH MATERIALS AND
      METHODS: This is a secondary analysis on previously collected data from 600
      participants with (n=300) and without (n=300) severe erosive tooth wear.
      Participants recruited from restorative clinics of King's College London Dental
      Institute (REC Ref 14/EM/1171) were questioned on their self-reported DH,
      frequency and timing of dietary acid intake, habits associated with consumption
      of dietary acids and tooth brushing habits. Erosive tooth wear was assessed using
      Basic Erosive Wear Examination (BEWE). Differences in diet and brushing habits
      between those with self-reported DH and those without were analysed using
      descriptives and logistic regression in SPSS vers. 24. RESULTS: Of those
      reporting with DH (n=272), a greater number spent >=10min eating fruit per
      sitting, (n=46) and had a drinking habit such as sipping, swishing or holding
      drinks in the mouth (n=72) compared to those without DH (n=26 OR 2.72, 95%CI
      [1.32-5.61], p=0.007 and n=38 OR2.33, 95%CI [1.40-3.88], p=0.001, respectively).
      More DH participants used a soft toothbrush (n=36) compared to those without DH
      (n=18 OR 2.35, 95%CI [1.20-4.59], p=0.013). No association was observed with
      frequency of daily toothbrushing or dietary acid intake. CONCLUSION: Contact time
      between the tooth and the acid may be a more important risk factor for DH
      compared to frequency of dietary acid intake or frequency of toothbrushing. Other
      possible aetiological factors should be considered. CLINICALTRIALS. GOV NUMBER:
      NCT02449434 CLINICAL SIGNIFICANCE: Increased contact time with dietary acids and
      sipping swishing or holding drinks in the mouth prior to swallowing should be
      addressed as an aetiological factor in DH. Toothpaste abrasivity and toothbrush
      filament stiffness may play a greater role in DH compared to frequency of
      toothbrushing.

PMID- 29017847
TI  - The biomarkers neuron-specific enolase and S100b measured the day following
      admission for severe accidental hypothermia have high predictive values for poor
      outcome.
AB  - AIM: The aim of the present study was to assess the ability of the biomarkers
      neuron-specific enolase (NSE) and S100 calcium-binding protein b (S100b) to
      predict mortality and poor neurologic outcome after 30days in patients admitted
      with severe accidental hypothermia. METHODS: Consecutive patients with severe
      accidental hypothermia, defined as a core temperature <32 degrees C, were
      included. Patients were treated with active rewarming and/or extracorporeal life
      support (ECLS) using extra corporeal circulation (ECC) and/or extra corporeal
      membrane oxygenation (ECMO). The day following admission blood was analyzed for
      NSE and S100b. Follow-up was conducted after 30days and poor neurologic outcome
      was defined as a Cerebral Performance Category (CPC) score of 3-5. The predictive
      value of NSE and S100b was assessed as the area under the receiver-operating
      characteristics curve (AUC). RESULTS: A total of 34 patients were admitted with a
      diagnosis of severe accidental hypothermia and 29 (85%) were resuscitated from
      cardiac arrest. ECLS was initiated in 27 (79%) of patients. The day following
      admission three (9%) patients had died and one (3%) patient was awake, and
      accordingly, NSE and S100b were analyzed in 30 unconscious and/or sedated
      patients. NSE and S100b achieved AUCs of 0.93 and 0.88, respectively, for
      prediction of 30day mortality and AUCs of 0.88 and 0.87, respectively, for
      prediction of poor neurologic outcome. CONCLUSIONS: In patients remaining
      unconscious the day following admission for severe accidental hypothermia, the
      biomarkers NSE and S100b appear to be solid predictors of mortality and poor
      neurologic outcome after 30days.

PMID- 29017848
TI  - Suppression of cotton leaf curl disease symptoms in Gossypium hirsutum through
      over expression of host-encoded miRNAs.
AB  - Cotton leaf curl disease (CLCuD), a major factor resulting in the enormous yield
      losses in cotton crop, is caused by a distinct monopartite begomovirus in
      association with Cotton leaf curl Multan betasatellite (CLCuMB). Micro(mi)RNAs
      are known to regulate gene expression in eukaryotes, including antiviral defense
      in plants. In a previous study, we had computationally identified a set of cotton
      miRNAs, which were shown to have potential targets in the genomes of Cotton leaf
      curl Multan virus (CLCuMuV) and CLCuMB at multiple loci. In the current study,
      effect of Gossypium arboreum-encoded miRNAs on the genome of CLCuMuV and CLCuMB
      was investigated in planta. Two computationally predicted cotton-encoded miRNAs
      (miR398 and miR2950) that showed potential to bind multiple Open Reading Frames
      (ORFs; C1, C4, V1, and non- coding intergenic region) of CLCuMuV, and (betaC1) of
      CLCuMB were selected. Functional validation of miR398 and miR2950 was done by
      overexpression approach in G. hirsutum var. HS6. A total of ten in vitro cotton
      plants were generated from independent events and subjected to biological and
      molecular analyses. Presence of the respective Precursor (pre)-miRNA was
      confirmed through PCR and Southern blotting, and their expression level was
      assessed by semi quantitative RT-PCR, Real Time quantitative PCR and northern
      hybridization in the PCR-positive lines. Southern hybridization revealed 2-4 copy
      integration of T-DNA in the genome of the transformed lines. Remarkably,
      expression of pre-miRNAs was shown up to 5.8-fold higher in the transgenic (T0)
      lines as revealed by Real Time PCR. The virus resistance was monitored following
      inoculation of the transgenic cotton lines with viruliferous whitefly (Bemisia
      tabaci) insect vector. After inoculation, four of the transgenic lines remained
      apparently symptom free. While a very low titre of viral DNA could be detected by
      Rolling circle amplification, betasatellite responsible for symptom induction
      could not be detected in any of the healthy looking transgenic lines. In this
      study for the first time, efficacy of the host (G. arboreum)-encoded miRNAs
      against CLCuD symptoms was experimentally demonstrated through overexpression of
      miR398 and miR2950 in G. hirsutum var. HS6 plants. Computational prediction of
      miRNAs targeting virus genome and their subsequent implication in translational
      inhibition or cleavage based suppression of viral mRNA via overexpression could
      help in generating virus resistant plants.

PMID- 29017846
TI  - Environmental toxicology of hydrogen sulfide.

PMID- 29017849
TI  - Production of HIV virus-like particles by transient transfection of CAP-T cells
      at bioreactor scale avoiding medium replacement.
AB  - Human-derived CAP-T cell line has been demonstrated to be a powerful platform for
      high-titer production of HIV virus-like particles (VLPs) by PEI-mediated
      transient transfection. Scale-up of transfection processes is key to ensure the
      necessary quantities for pre-clinical and clinical testing. One of the major
      operational challenges of large-scale transient transfection is the medium
      replacement step that is often required before transfection. In this work, CAP-T
      cells were cultured in 1L bioreactor with addition of sodium bicarbonate and
      surface aeration, which were observed to improve cell state for transfection.
      Remarkably, the medium replacement step was avoided by culturing the cells in a
      combination of media (FreeStyleF17+1% of PEM) compatible with cell growth and PEI
      mediated transient transfection. In the conditions developed in this work,
      0.5*106cells/mL were seeded in 1L bioreactor. Two days later, ~2*106cells/mL were
      transfected without medium exchange, using 0.5pg of DNA/cell and 3pg of PEI/cell.
      Transfection efficiency and VLP production comparable to shake flasks were
      obtained with a production of 4*1010VLPs/mL. This novel strategy significantly
      simplifies large-scale transient transfection, while suitable cell growth,
      transfection efficiency, and high quality VLP production are achieved.

PMID- 29017850
TI  - Expression of estrogen receptors in female rainbow trout (Oncorhynchus mykiss)
      during first ovarian development and under dense rearing condition.
AB  - To study the expression of four estrogen receptor genes (eralpha1, eralpha2,
      erbeta1, erbeta2) of female rainbow trout (Oncorhynchus mykiss) during first
      ovarian development, trouts were sampled from different ovarian stages. Serum E2
      (estradiol) was measured by ELISA and estrogen receptors mRNA expression were
      examined by qRT-PCR. Our results showed a close association between increased
      eralpha1 and vitellogenin mRNA expression during ovarian maturation and increased
      eralpha2 mRNA expression in mature ovarian stages. Correlation analysis revealed
      that a negative relationship between serum E2 and ovarian erbeta1 (or hepatic
      erbeta2), but ovarian erbeta2 mRNA expression was relatively unchanged during
      first ovarian development. Trout were also reared in different densities as
      stocking density 1, 2 and 3 (SD1, 4.6-31.1 kg/m3; SD2, 6.6-40.6 kg/m3; SD3, 8.6
      49.3 kg/m3) to elucidate effects of high density on estrogen receptor expression.
      Histology observation showed ovarian development of trout in higher densities
      were retard with a relatively early stage and fewer vitellogenin accumulation.
      Trout in high densities showed significantly decreased serum E2, eralpha mRNA
      expression and increasing trends of erbeta mRNA expression. A noticeable increase
      of ovarian erbeta2 mRNA expression was seen in trout when density is approaching
      to 50 kg/m3. In conclusion, we may hypothesize that increased erbeta mRNA
      expression triggered by high density result in decreased eralpha mRNA expression
      and vitellogenesis. As a result, ovarian development in higher densities was
      retard.

PMID- 29017851
TI  - Seasonal ovarian immunolocalization of neuropeptide Y and its role in
      steriodogenesis in Asian catfish, Clarias batrachus.
AB  - The present study was undertaken to examine the cellular localization and
      potential steroidogenic role of neuropeptide Y (NPY) in the ovary of the
      freshwater catfish, Clarias batrachus. NPY-immunoreaction was observed in the
      follicular cells (granulosa and thecal cells) in the growing ovarian follicles,
      and the intensity of staining increased steadily from the initiation of
      follicular development until follicles were fully grown. Thereafter as follicles
      matured the stain intensity decreased. Positive correlations were found between
      NPY expression and the ovarian levels of 17beta-estradiol, testosterone, and
      activities of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta
      hydroxysteroid dehydrogenase (17beta-HSD) in the ovary. In vitro NPY treatment
      stimulated the production of the two steroids and the activities of two enzymes.
      This is the first report of NPY immunoreactivity at the cellular level in the
      fish ovary and implicates this orexigenic peptide in the modulation of ovarian
      steroidogenesis.

PMID- 29017852
TI  - An Augmented Reality magic mirror as additive teaching device for gross anatomy.
AB  - When preparing young medical students for clinical activity, it is indispensable
      to acquaint them with anatomical section images which enable them to use the
      clinical application of imaging methods. A new Augmented Reality Magic Mirror (AR
      MM) system, which provides the advantage of a novel, interactive learning tool in
      addition to a regular dissection course, was therefore tested and evaluated by
      880 first-year medical students as part of the macroscopic anatomy course in
      2015/16 at Ludwig-Maximilians-Universitat (LMU) in Munich. The system consists of
      an RGB-D sensor as a real-time tracking device, which enables the system to link
      a deposited section image to the projection of the user's body, as well as a
      large display mimicking a real-world physical mirror. Using gesture input, the
      users have the ability to interactively explore radiological images in different
      anatomical intersection planes. We designed a tutorial during which students
      worked with the system in groups of about 12 and evaluated the results.
      Subsequently, each participant was asked to assess the system's value by filling
      out a Likert-scale questionnaire. The respondents approved all statements which
      stressed the potential of the system to serve as an additional learning resource
      for anatomical education. In this case, emphasis was put on active learning, 3
      dimensional understanding, and a better comprehension of the course of
      structures. We are convinced that such an AR MM system can be beneficially
      installed into anatomical education in order to prepare medical students more
      effectively for the clinical standards and for more interactive, student-centered
      learning.

PMID- 29017853
TI  - Rampant polyphyly in the Arracacia clade (Apiaceae) and an assessment of the
      phylogenetic utility of 20 noncoding plastid loci.
AB  - The Arracacia clade (Apiaceae, Apioideae) is a heterogeneous assemblage of 12
      genera, comprising 111 known species distributed in high montane temperate and
      sub-alpine habitats of meso- and South America. Previous studies have indicated
      that the genera Arracacia, Coulterophytum, and Prionosciadium are polyphyletic,
      but for the most part relationships among the members of the clade are largely
      unknown. Initially, cladistic analyses of nrDNA ITS sequences were carried out on
      212 accessions (122 taxa), representing 92 species of the Arracacia clade and
      outgroups from the closely-related paramo genera Cotopaxia, Niphogeton, and
      Perissocoeleum and members of the Perennial Endemic North American clade and its
      allies. Using the ITS results to inform sampling of a small subset of taxa, a
      pilot study examining the phylogenetic utility of 20 noncoding chloroplast loci
      was subsequently performed to identify those regions most useful at resolving
      relationships. A cost-benefit analysis determined that five loci (trnQ-5'rps16,
      trnD-trnT, rpl32-trnL, psbD-trnT, ndhA intron) would maximize resolution and
      branch support in the clade. Cladistic analyses of four of these loci (trnQ
      5'rps16, trnD-trnT, rpl32-trnL, ndhA intron) and the ITS region, separately and
      combined, revealed that Arracacia, Coaxana, Coulterophytum, Prionosciadium, and
      Rhodosciadium are each polyphyletic and that Donnellsmithia and Myrrhidendron are
      each monophyletic. Although most relationships in the Arracacia clade and among
      the closely-related genera Cotopaxia, Niphogeton, and Perissocoeleum are poorly
      resolved and supported, ten groups are recognized for future revisionary studies.
      Polyploidy and rapid species radiation have likely confounded generic
      circumscriptions and interpretation of relationships.

PMID- 29017854
TI  - PEGylated TRAIL ameliorates experimental inflammatory arthritis by regulation of
      Th17 cells and regulatory T cells.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) is a death ligand that can induce
      apoptosis in cells expressing its cognate death receptors (DRs). Previously, we
      demonstrated the therapeutic potential of recombinant human TRAIL in experimental
      rheumatoid arthritis (RA) models. However, the mechanisms of how DR-mediated
      apoptosis elicits these actions is not known. Here, we show that systemically
      administering a potent, long-acting PEGylated TRAIL (TRAILPEG) is profoundly anti
      rheumatic against two complementary experimental RA mouse models, collagen
      induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA), via
      targeting IL-17 secreting Th17 cells and regulatory T cells (Treg). Systemic
      administration of TRAILPEG after disease onset ameliorated the severity of
      inflammatory arthritis including arthritis indices, paw thickness, cartilage
      damage and neutrophil infiltration in both CIA and CAIA models. Additionally, the
      levels of inflammatory molecules (p-p65, ICAM-1, Cox-2, MMP3, and iNOS), pro
      inflammatory cytokines (TNF-alpha, IL-1beta, IFN-gamma, IL-6, IL-17) and
      accumulation of activated macrophages were significantly reduced after the
      TRAILPEG treatment. Importantly, TRAILPEG decreased the number of pro
      inflammatory Th17 cells in inflamed arthritic joints through TRAIL-induced
      apoptosis while increasing anti-inflammatory Treg population in vivo. These
      results suggest that TRAILPEG ameliorates autoimmunity by targeting the Th 17
      Tregs axis, making it a promising candidate drug for the treatment of RA.

PMID- 29017855
TI  - Role of neuromedin U in accelerating of non-alcoholic steatohepatitis in mice.
AB  - Neuromedin U (NMU), a neuropeptide originally isolated from porcine spinal cord,
      has multiple physiological functions and is involved in obesity and inflammation.
      Excessive fat accumulation in the liver leads to non-alcoholic fatty liver
      disease (NAFLD) and non-alcoholic steatohepatitis (NASH), which is closely
      associated with obesity. NAFLD and NASH develop and progress via complex
      pathophysiological processes, and it remains unclear to what extend the NMU
      system contributes to the risk of obesity-related disorders such as NAFLD and
      NASH. Here, we demonstrate that the NMU system plays a role in NAFLD/NASH
      pathogenesis. In the normal mouse liver, NMU mRNA was not detectable, and
      expression of the mRNA encoding neuromedin U receptor 1 (NMUR1), the peripheral
      receptor of NMU, was low. However, the expression of both was significantly
      increased in the livers of NASH mice. Furthermore, overproduction of NMU induced
      the mouse liver by hydrodynamic injection, exacerbated NASH pathogenesis. These
      data indicate a novel role for the peripheral NMU system, providing new insights
      into the pathogenesis of NAFLD/NASH.

PMID- 29017856
TI  - Planning an innovation marathon at an infectious disease conference with results
      from the International Meeting on Emerging Diseases and Surveillance 2016
      Hackathon.
AB  - A hackathon is best described as an 'innovation marathon'. Derived from the words
      'hacking' and 'marathon', it brings together multidisciplinary teams to
      collaborate intensely over a short period of time to define a problem, devise a
      solution, and design a working prototype. International scientific meetings are
      conducive to successful hackathons, providing an audience of expert professionals
      who describe challenges and ensure the proposed solutions address end-user needs.
      Collaborations with local organizations and academic centers are crucial to
      attracting complementary specialties such as IT advisors, engineers, and
      entrepreneurs to develop sustainable projects. The core process of first
      identifying and deconstructing a problem followed by solution iteration is
      applicable to challenges at workplaces around the world. Ultimately, this model
      can be used to drive innovation and catalyze change in the global health
      community. The planning, execution, and outcomes of a hackathon event organized
      in conjunction with the International Meeting on Emerging Diseases and
      Surveillance (IMED 2016) are described in this article. Physicians, public health
      practitioners, veterinarians, IT professionals, engineers, and entrepreneurs came
      together for 2days to develop solutions at the intersection of emerging
      infectious diseases and climate change. Projects that resulted from the IMED 2016
      Hackathon included environmental impact assessment software for humanitarian
      organization relief efforts; enhanced communication tools to prevent disease
      outbreaks; a participatory mobile application to speed the elimination of rabies
      in Indonesia; integrated disease surveillance platforms; and an improved search
      function for infectious disease outbreak reports in the ProMED-mail network.

PMID- 29017859
TI  - A network meta-analysis of updated haemostatic strategies for hysterectomy: A
      response to the authors of IJS-D-17-01065.

PMID- 29017860
TI  - High BMI and male sex as risk factor for increased short-term renal impairment in
      living kidney donors. A response to comments raised.

PMID- 29017861
TI  - Propensity score-matched analysis of the endoscopic bilateral axillo-breast
      approach (BABA) versus conventional open thyroidectomy in patients with benign or
      intermediate fine-needle aspiration cytology results, a retrospective study.
AB  - BACKGROUND: The purpose of this study was to compare the surgical outcomes of
      endoscopic bilateral axillo-breast approach (BABA) to conventional open
      thyroidectomy (COT) in patients who had thyroid nodule(s) with a benign or
      intermediate fine-needle aspiration cytology (FNAC) results. MATERIALS AND
      METHODS: All patients with benign or intermediate thyroid nodule(s) who underwent
      BABA (n = 95) or COT (n = 262) between 2008 and 2015 were reviewed. Then, 1:1
      propensity score matching was performed, and 66 matched pairs were obtained.
      Surgical outcomes were then compared. RESULTS: Before matching, patients in the
      BABA group were significantly younger (36.5 vs. 50.7 years, p < 0.000),
      predominantly female (97.9% vs. 69.8%, p < 0.000), had smaller tumours (2.1 vs.
      2.8 cm, p = 0.002) and more commonly underwent hemithyroidectomy (88.4% vs.
      70.6%, p < 0.000) than those in the COT group. After matching, all
      clinicopathological characteristics were equivalent. BABA was found to be
      significantly associated with longer operative time (125.3 vs. 79.8 min, p <
      0.000), greater drainage volume (132.9 vs. 59.1 ml, p < 0.000), longer
      postoperative hospital stay (3.1 vs. 2.2 days, p < 0.000), and higher average
      total medical expense (4000 vs. 3200 US$). However, the incidence of
      complications did not differ between the groups. CONCLUSION: BABA is comparable
      to COT in terms of complications and is safe and feasible when performed by
      experienced surgeons and for carefully selected patients who are concerned about
      neck scarring. However, the operative time and postoperative hospital stay are
      significantly longer, which may increase medical expenses.

PMID- 29017857
TI  - Administration of 5-methoxyindole-2-carboxylic acid that potentially targets
      mitochondrial dihydrolipoamide dehydrogenase confers cerebral preconditioning
      against ischemic stroke injury.
AB  - The objective of this study was to investigate a possible role of mitochondrial
      dihydrolipoamide dehydrogenase (DLDH) as a chemical preconditioning target for
      neuroprotection against ischemic injury. We used 5-methoxyindole-2-carboxylic
      acid (MICA), a reportedly reversible DLDH inhibitor, as the preconditioning agent
      and administered MICA to rats mainly via dietary intake. Upon completion of 4
      week's MICA treatment, rats underwent 1h transient ischemia and 24h reperfusion
      followed by tissue collection. Our results show that MICA protected the brain
      against ischemic stroke injury as the infarction volume of the brain from the
      MICA-treated group was significantly smaller than that from the control group.
      Data were then collected without or with stroke surgery following MICA feeding.
      It was found that in the absence of stroke following MICA feeding, DLDH activity
      was lower in the MICA treated group than in the control group, and this decreased
      activity could be partly due to DLDH protein sulfenation. Moreover, DLDH
      inhibition by MICA was also found to upregulate the expression of NAD(P)H
      ubiquinone oxidoreductase 1(NQO1) via the Nrf2 signaling pathway. In the presence
      of stroke following MICA feeding, decreased DLDH activity and increased Nrf2
      signaling were also observed along with increased NQO1 activity, decreased
      oxidative stress, decreased cell death, and increased mitochondrial ATP output.
      We also found that MICA had a delayed preconditioning effect four weeks post MICA
      treatment. Our study indicates that administration of MICA confers chemical
      preconditioning and neuroprotection against ischemic stroke injury.

PMID- 29017858
TI  - The transcriptional response of skin to fluorescent light exposure in viviparous
      (Xiphophorus) and oviparous (Danio, Oryzias) fishes.
AB  - Differences in light sources are common in animal facilities and potentially can
      impact experimental results. Here, the potential impact of lighting differences
      on skin transcriptomes has been tested in three aquatic animal models commonly
      utilized in biomedical research, (Xiphophorus maculatus (platyfish), Oryzias
      latipes (medaka) and Danio rerio (zebrafish). Analysis of replicate comparative
      RNA-Seq data showed the transcriptional response to commonly utilized 4100K or
      "cool white" fluorescent light (FL) is much greater in platyfish and medaka than
      in zebrafish. FL induces genes associated with inflammatory and immune responses
      in both medaka and zebrafish; however, the platyfish exhibit suppression of genes
      involved with immune/inflammation, as well as genes associated with cell cycle
      progression. Furthermore, comparative analyses of gene expression data from
      platyfish UVB exposures, with medaka and zebrafish after exposure to 4100K FL,
      show comparable effects on the same stress pathways. We suggest the response to
      light is conserved, but that long-term adaptation to species specific
      environmental niches has resulted in a shifting of the wavelengths required to
      incite similar "genetic" responses in skin. We forward the hypothesis that the
      "genetic perception" of light may have evolved differently than ocular perception
      and suggest that light type (i.e., wavelengths emitted) is an important parameter
      to consider in experimental design.

PMID- 29017862
TI  - Emergency repair of upper extremity large soft tissue and vascular injuries with
      flow-through anterolateral thigh free flaps.
AB  - BACKGROUND/OBJECTIVES: Complex extremity trauma commonly involves both soft
      tissue and vascular injuries. Traditional two-stage surgical repair may delay
      rehabilitation and functional recovery, as well as increase the risk of
      infections. We report a single-stage reconstructive surgical method that repairs
      soft tissue defects and vascular injuries with flow-through free flaps to improve
      functional outcomes. METHODS: Between March 2010 and December 2016 in our
      hospital, 5 patients with severe upper extremity trauma received single-stage
      reconstructive surgery, in which a flow-through anterolateral thigh free flap was
      applied to repair soft tissue defects and vascular injuries simultaneously. Cases
      of injured artery were reconstructed with the distal trunk of the descending
      branch of the lateral circumflex femoral artery. A segment of adjacent vein was
      used if there was a second artery injury. Patients were followed to evaluate
      their functional recoveries, and received computed tomography angiography
      examinations to assess peripheral circulation. RESULTS: Two patients had post
      operative thumb necrosis; one required amputation, and the other was healed after
      debridement and abdominal pedicle flap repair. The other 3 patients had no major
      complications (infection, necrosis) to the recipient or donor sites after
      surgery. All the patients had achieved satisfactory functional recovery by the
      end of the follow-up period. Computed tomography angiography showed adequate
      circulation in the peripheral vessels. CONCLUSIONS: The success of these cases
      shows that one-step reconstructive surgery with flow-through anterolateral thigh
      free flaps can be a safe and effective treatment option for patients with complex
      upper extremity trauma with soft tissue defects and vascular injuries.

PMID- 29017863
TI  - Surgical volunteerism as a collaborative teaching activity can benefit surgical
      residents in low-middle income countries.
AB  - Surgical care is desperately needed in low-middle income countries (LMIC). Due to
      small numbers of faculty in local training programs, residents have limited
      exposure to subspecialists. We describe a teaching activity between visiting
      surgeons from the U.S. and a residency program in Malawi as an example for how
      surgeons in high income countries can meaningfully contribute. A short-term
      education activity was developed where residents participated in a pre-test on
      pediatric surgical management, lectures, intra-operative instruction, bedside
      rounds and a post-test. Five residents participated and all intend to practice in
      sub-Saharan Africa. All residents improved their scores from the pre-test to post
      test (mean 44%-91%). The residency program performs approximately 1200 major
      surgical cases and 800 minor surgical procedures each year, representing a broad
      range of general surgery. Additionally, the residents encounter a broad range of
      pathology. Short-term mentorship activities in partnership with an established
      training program can enhance surgical resident education in LMIC, particularly
      for subspecialty care.

PMID- 29017864
TI  - Clinicopathological and prognostic significance of FoxM1 in gastric cancer: A
      meta-analysis.
AB  - BACKGROUND: The relationship between expression of FoxM1 and clinical parameters
      of patients with gastric cancer (GC) has yet to be fully established. METHODS: A
      systematic search was performed. Odds ratio (OR) and confidence interval (CI)
      were used to assess association between expression of FoxM1 and clinical
      parameters and the prognostic value of patients with GC. RESULTS: Eight studies
      involving 529 patients with GC were identified. Overall, the pooled results
      showed that expression of FoxM1 was associated with TNM stage (OR: 0.482, 95%CI:
      0.275-0.845, P = 0.011), depth of invasion (OR: 0.617, 95%CI: 0.382-0.998, P =
      0.049) and lymph node metastasis (OR: 2.084, 95%CI: 1.305-3.328, P = 0.002) in
      the patients with GC. Whereas, expression of FoxM1 was not associated with gender
      (OR: 1.143, 95%CI: 0.726-1.799, P = 0.564) and tumors' differentiation (OR:
      0.991, 95%CI: 0.624-1.575, P = 0.971) of GC. Expression of FoxM1 was also
      associated with poor prognosis of overall survival (OS) in the patients with GC
      (one year OS: OR: 0.218, 95%CI: 0.103-0.459, P = 0.000; three years OS: OR:
      0.178, 95%CI: 0.093-0.340, P = 0.000; five years OS: OR: 0.180, 95%CI: 0.095
      0.341, P = 0.000). CONCLUSION: Expression of FoxM1 is associated with TNM stage,
      depth of invasion, lymph node metastasis and poor prognosis of the patients with
      GC.

PMID- 29017865
TI  - BMI and short-term outcomes in living kidney donors: Where surgery and nephrology
      meet: High BMI and male sex as risk factor for increased short-term renal
      impairment in living kidney donors - Retrospective analysis of 289 consecutive
      cases.

PMID- 29017869
TI  - Risk assessment and quality improvement of liquid waste management in Taiwan
      University chemical laboratories.
AB  - The policy of establishing new universities across Taiwan has led to an increase
      in the number of universities, and many schools have constructed new laboratories
      to meet students' academic needs. In recent years, there has been an increase in
      the number of laboratory accidents from the liquid waste in universities.
      Therefore, how to build a safety system for laboratory liquid waste disposal has
      become an important issue in the environmental protection, safety, and hygiene of
      all universities. This study identifies the risk factors of liquid waste disposal
      and presents an agenda for practices to laboratory managers. An expert
      questionnaire is adopted to probe into the risk priority procedures of liquid
      waste disposal; then, the fuzzy theory-based FMEA method and the traditional FMEA
      method are employed to analyze and improve the procedures for liquid waste
      disposal. According to the research results, the fuzzy FMEA method is the most
      effective, and the top 10 potential disabling factors are prioritized for
      improvement according to the risk priority number (RNP), including "Unclear
      classification", "Gathering liquid waste without a funnel or a drain pan", "Lack
      of a clearance and transport contract", "Liquid waste spill during delivery",
      "Spill over", "Decentralized storage", "Calculating weight in the wrong way",
      "Compatibility between the container material and the liquid waste", "Lack of
      dumping and disposal tools", and "Lack of a clear labels for liquid waste
      containers". After tracking improvements, the overall improvement rate rose to
      60.2%.

PMID- 29017866
TI  - as-PSOCT: Volumetric microscopic imaging of human brain architecture and
      connectivity.
AB  - Polarization sensitive optical coherence tomography (PSOCT) with serial
      sectioning has enabled the investigation of 3D structures in mouse and human
      brain tissue samples. By using intrinsic optical properties of back-scattering
      and birefringence, PSOCT reliably images cytoarchitecture, myeloarchitecture and
      fiber orientations. In this study, we developed a fully automatic serial
      sectioning polarization sensitive optical coherence tomography (as-PSOCT) system
      to enable volumetric reconstruction of human brain samples with unprecedented
      sample size and resolution. The 3.5 MUm in-plane resolution and 50 MUm through
      plane voxel size allow inspection of cortical layers that are a single-cell in
      width, as well as small crossing fibers. We show the abilities of as-PSOCT in
      quantifying layer thicknesses of the cerebellar cortex and creating microscopic
      tractography of intricate fiber networks in the subcortical nuclei and internal
      capsule regions, all based on volumetric reconstructions. as-PSOCT provides a
      viable tool for studying quantitative cytoarchitecture and myeloarchitecture and
      mapping connectivity with microscopic resolution in the human brain.

PMID- 29017867
TI  - Volumetric reconstruction from printed films: Enabling 30 year longitudinal
      analysis in MR neuroimaging.
AB  - Hospitals often hold historical MR image data printed on films without being able
      to make it accessible to modern image processing techniques. Having the
      possibility to recover geometrically consistent, volumetric images from scans
      acquired decades ago will enable more comprehensive, longitudinal studies to
      understand disease progressions. In this paper, we propose a consistent framework
      to reconstruct a volumetric representation from printed films holding thick
      single-slice brain MR image acquisitions dating back to the 1980's. We introduce
      a flexible framework based on semi-automatic slice extraction, followed by
      automated slice-to-volume registration with inter-slice transformation
      regularisation and slice intensity correction. Our algorithm is robust against
      numerous detrimental effects being present in archaic films. A subsequent,
      isotropic total variation deconvolution technique revitalises the visual
      appearance of the obtained volumes. We assess the accuracy and perform the
      validation of our reconstruction framework on a uniquely long-term MRI dataset
      where a ground-truth is available. This method will be used to facilitate a
      robust longitudinal analysis spanning 30 years of MRI scans.

PMID- 29017870
TI  - Biogas purification with biomass ash.
AB  - The aim of the study was to investigate the option to purify biogas from small
      scale biogas plants by entrapping CO2 and H2S with regionally available biomass
      ash. Connected to the existing biogas plant Neustift (Tyrol) wood ash placed in a
      1 m3 container was used as a trap for CO2 and H2S in the biogas. With the process
      conditions chosen, for a period of a few hours CO2 was trapped resulting in pure
      methane. The removal of H2S was much longer-lasting (up to 34 d). The cumulative
      H2S uptake by the biomass ash ranged from 0.56 to 1.25 kg H2S per ton of ash. The
      pH of the ash and the leachability of Lead and Barium were reduced by the
      flushing with biogas, however toxicity towards plants was increased thus reducing
      the potential of ash use in agriculture. It can be concluded that biomass ash may
      be used for removal of hydrogen sulphide from biogas in small and medium biogas
      plants. The economic evaluation, however, indicated that the application of this
      system is limited by transport distances for the ash and its potential use
      afterwards.

PMID- 29017871
TI  - Theoretical analysis of municipal solid waste treatment by leachate recirculation
      under anaerobic and aerobic conditions.
AB  - Long-term emissions of Municipal Solid Waste (MSW) landfills are a burden for
      future generations because of the required long-term aftercare. To shorten
      aftercare, treatment methods have to be developed that reduce long-term
      emissions. A treatment method that reduces emissions at a lysimeter scale is re
      circulation of leachate. However, its effectiveness at the field scale still
      needs to be demonstrated. Field scale design can be improved by theoretical
      understanding of the processes that control the effectiveness of leachate
      recirculation treatment. In this study, the simplest and most fundamental sets of
      processes are distilled that describe the emission data measured during aerobic
      and anaerobic leachate recirculation in lysimeters. A toolbox is used to select
      essential processes with objective performance criteria produced by Bayesian
      statistical analysis. The controlling processes indicate that treatment
      efficiency is mostly affected by how homogeneously important reactants are spread
      through the MSW during treatment. A more homogeneous spread of i.e. oxygen or
      methanogens increases the total amount of carbon degraded. Biodegradable carbon
      removal is highest under aerobic conditions, however, the hydrolysis rate
      constant is lower which indicates that hydrolysis is not enhanced intrinsically
      in aerobic conditions. Controlling processes also indicate that nitrogen removal
      via sequential nitrification and denitrification is plausible under aerobic
      conditions as long as sufficient biodegradable carbon is present in the MSW.
      Major removal pathways for carbon and nitrogen are indicated which are important
      for monitoring treatment effectiveness at a field scale. Optimization strategies
      for field scale application of treatments are discussed.

PMID- 29017868
TI  - Rates of Anovulation in Adolescents and Young Adults with Moderate to Severe
      Primary Dysmenorrhea and Those without Primary Dysmenorrhea.
AB  - STUDY OBJECTIVE: To evaluate rates of presumptive anovulation in eumenorrheic
      adolescents and young adults with moderate to severe primary dysmenorrhea and
      those without primary dysmenorrhea. DESIGN: Participants completed luteinizing
      hormone surge ovulation predictor test kits. Anovulatory cycles were defined by
      never receiving a positive result before the next menstrual period; participants
      were grouped as anovulatory if they experienced at least 1 anovulatory cycle
      during study participation. Participants rated daily level of menstrual pain on a
      0-10 numeric rating scale. SETTING: A university-based clinical research
      laboratory. PARTICIPANTS: Thirty-nine adolescents and young adults (ages 16-24)
      with primary dysmenorrhea and 52 age-matched control girls. INTERVENTIONS AND
      MAIN OUTCOME MEASURES: Rates of presumptive anovulation. RESULTS: One hundred
      sixty-eight cycles were monitored, 29.8% (N = 50) of which were anovulatory
      (37.1% [39/105] vs 17.5% [11/63] of cycles in control and dysmenorrhea groups,
      respectively). During study participation, control girls were significantly more
      likely to have had at least 1 anovulatory cycle than were girls with primary
      dysmenorrhea (44.2% [23/52] vs 17.9% [7/39] of participants, respectively; P <
      .01). Cycle length and number of bleeding days between ovulatory and anovulatory
      cycles were similar. The primary dysmenorrhea group's maximum menstrual pain
      ratings did not differ between ovulatory and anovulatory cycles (4.77 and 4.36,
      respectively; P > .05). CONCLUSION: Our data support previous findings of
      increased rates of ovulation in primary dysmenorrhea. However, menstruation after
      anovulatory cycles can be as painful as menstruation after ovulatory cycles.
      These data support the idea that regular menses do not necessarily indicate that
      a normal ovulatory cycle has occurred. Previous implications that ovulation is
      necessary for the development of substantial menstrual pain are incomplete.

PMID- 29017873
TI  - Rheological characterisation of biologically treated and non-treated putrescible
      food waste.
AB  - Food waste is gaining increasing attention worldwide due to growing concerns over
      its environmental and economic costs. Understanding the rheological behaviour of
      food waste is critical for effective processing so rheological measurements were
      carried out for different food waste compositions at 25, 35 and 45  degrees C.
      Food waste samples of various origins (carbohydrates, vegetables & fruits, and
      meat), anaerobically digested and diluted samples were used in this study. The
      results showed that food waste exhibits shear-thinning flow behaviour and
      viscosity of food waste is a function of temperature and composition. The
      composition of food waste affected the flow properties. Viscosity decreased at a
      given temperature as the proportion of carbohydrate increased. This may be due to
      the high water content of vegetable & fruits as the total solids fraction is
      likely to be a key controlling factor of the rheology. The Herschel-Bulkley model
      was used successfully to model food waste flow behaviour. Also, a higher strain
      was needed to break down the structure of the food waste as digestion time
      increased.

PMID- 29017872
TI  - Anaerobic digestion of cheese whey: Energetic and nutritional potential for the
      dairy sector in developing countries.
AB  - Cheese whey (CW) is the main waste generated in the cheesemaking process and has
      high organic matter content and acidity. Therefore, CW disposal is a challenge
      for small to medium enterprises (SMEs) in the dairy industry that do not have any
      type of treatment plant. Anaerobic digestion (AD) is an attractive process for
      solving this problem. The aim of this research was to determine the biomethane
      and struvite precipitation potentials of CW from four dairy SMEs. First, changes
      in CW properties (organic matter and pH) were evaluated. Second, biomethane and
      struvite potentials were assessed using cattle slurry as inoculum. The organic
      matter in CW varied from 40 to 65gVS/kg, 65 to 140g COD/L, and 2 to 10g/L for
      VFAs depending on the sampling time and type of sample. The pH of the CW samples
      ranged from 3 to 6.5. In the anaerobic biodegradability analysis, methane yields
      reached 0.51 to 0.60L CH4/g VSadded, which represented electrical and caloric
      potentials of 54 and 108kWh/m3 for CW, respectively. Organic matter removal in
      all experiments was above 83%. Moreover, anaerobic digestates presented NH4+/PO43
      molar ratios between 2.6 and 4.0, which are adequate for struvite precipitation
      with potential production of 8.5-10.4g struvite/L CW. Finally, the use of biogas
      as energetic supplement and struvite as soil fertilizer, represents economics
      saves of US$ 6.91/m3 CW and US$ 5.75/m3 CW in therms of electricity and
      fertilizer use, respectively. The energetic, agricultural and economic
      potentials, evidence that AD process is a feasible alternative for cheese whey
      treatment.

PMID- 29017874
TI  - Temporal relationships between food acquisition and voluntary exercise in mice.
AB  - Patterns of operant food acquisition in a closed economy and bouts of either
      voluntary wheel running (WR) or spontaneous locomotor activity in a standard
      condition (SC) with no wheel were examined in young adult male and female C57BL/6
      mice across a range of nose poke prices (FUP) per food pellet. Both sexes showed
      vigorous WR or locomotor activity. At each FUP, WR groups had higher food intake
      than SC groups. Despite substantially higher mean body weight of males compared
      with females, intakes and activity did not differ by sex in the SC groups and
      males lost weight more rapidly as FUP increased. In contrast, WR males ran ~33%
      further per day than females, increased their food intake (above that of SC
      counterparts) more than females, and lost less body weight than SC males. By
      parsing the night in four 3h epochs it was found that food intake declined
      progressively through the night in both WR and SC mice and that the hyperphagia
      of WR relative to SC groups was most evident early in the night, coincident with
      highest activity. No large or systematic sex differences were revealed in these
      temporal analyses. Analysis of data at 60s resolution showed that pellet
      acquisition occurred in many small or short bouts, the timing of which was either
      intercalated or concurrent with either locomotor activity or WR. The results show
      that increased eating due to WR occurs concurrently with maximum running, and
      with no evidence of delayed compensation.

PMID- 29017875
TI  - Hierarchical dynamics influence the distribution of immature black flies
      (Diptera: Simuliidae).
AB  - Adult black flies (Simuliidae) are medically important insects and they are the
      sole vector of Onchocerca volvulus. Immature black flies are major components of
      aquatic macroinvertebrate assemblages in streams and play a vital role in
      nutrient dynamics. In this study, we examined effect of hierarchical dynamics
      (spatio-temporal pattern) on the distribution of immature black flies in South
      Indian streams. The sampling was done in streams of Western Ghats, South India. A
      total of 16 species belong to two subgenera: Simulium (10 species) and
      Gowmphostilbia (6 species) of Simulium were observed. Alpha diversity indices
      were analyzed, which indicate the abundance and species richness between sampling
      sites. Non-parametric analysis recognized the key environmental variables
      including latitude and stream order. Subsequently, the monsoon influences the
      larval assemblages and its association was high in leaf litter as revealed
      through statistical analyses. Although the members of the immature black fly
      assemblage with different environmental factors, they are very closely related to
      spatial and temporal organization and secondarily with other factors prevailing
      in streams.

PMID- 29017876
TI  - Animal and human tungiasis-related knowledge and treatment practices among animal
      keeping households in Bugiri District, South-Eastern Uganda.
AB  - BACKGROUND: Zoonotic tungiasis caused by Tunga penetrans remains a serious public
      and animal health problem among endemic villages in Uganda and many sub Saharan
      African countries. Studies on human and animal tungiasis-related knowledge and
      treatment practices in endemic communities have never been undertaken, a
      limitation to development of sustainable control measures. METHODS: A cross
      sectional study using semi-structured questionnaires (Supplementary file S1) was
      conducted among 236 animal rearing households in 10 endemic villages in Bugiri
      District, South-Eastern Uganda. Focus group discussions and observation
      checklists were used to validate and clarify the findings. RESULTS: Most
      respondents knew the aetiology (89.4%), clinical signs (98%) and the ecology of
      T. penetrans as well as the major risk factors of human tungiasis (65.2%). In
      contrast, very few respondents were aware of animal tungiasis. Only 4.8% of those
      with infected animals on the compound knew that some of their animals were
      infected and 13.6% of the respondents had ever seen tungiasis-affected animals.
      Pigs (13.1%, n=31) and dogs (0.85%, n=2) were the only T. penetrans animal hosts
      known to animal owners. Affected humans were treated by extraction of embedded
      sand fleas using non-sterile sharp instruments in all households that reported
      occurrence of human tungiasis at least once (n=227). Also, affected animals were
      mainly treated by mechanical removal of embedded sand fleas in households that
      have ever experienced animal tungiasis (four out of 12; 33.3%). In a few
      instances, plant and animal pesticides (n=3) and other chemicals such as grease,
      paraffin and wood preservative (n=3) were also used to treat animal tungiasis.
      CONCLUSION: The study revealed a high level of knowledge on human tungiasis but
      inadequate knowledge on the zoonotic nature of tungiasis. Commonly applied
      methods for treatment of human and animal tungiasis are a health hazard by
      themselves. Concerted i.e. One Health-based efforts aiming at promoting
      appropriate treatment of tungiasis, adequate living conditions and increased
      awareness on tungiasis in the communities are indicated in order to eliminate
      tungiasis-associated disease.

PMID- 29017877
TI  - Therapeutic efficacy of artesunate - amiodaquine for treating uncomplicated
      falciparum malaria at Ghindae Zonal Referral Hospital, Eritrea.
AB  - INTRODUCTION: The aim of this study was to assess the efficacy of artesunate
      amodiaquine (AS+AQ) which is the first-line treatment for uncomplicated
      falciparum malaria in Eritrea. MATERIALS AND METHODS: The study was conducted
      from December 2014 to March 2015 in Ghindae Zonal Referral Hospital in Northern
      Red Sea Zone. Out of 481 patients screened, 103 were enrolled in the study. The
      therapeutic efficacy test was done as per the WHO protocol for a period of 28days
      of follow-up. RESULTS: The PCR-uncorrected treatment outcome was classified as
      adequate clinical and parasitological response (ACPR) in 95 patients, which meant
      the cure rate was 96.0 (95% CI: 89.7%-98.5%) after survival analysis.
      CONCLUSIONS: Therapeutic efficacy of AS+AQ still meets the WHO efficacy criteria
      for its continued use in the study area as the first-line drug against
      uncomplicated falciparum malaria. However, further studies are needed using
      correction with molecular markers to monitor therapeutic efficacy of antimalarial
      drugs in this area.

PMID- 29017878
TI  - Andean cutaneous leishmaniasis (Andean-CL, uta) in Peru and Ecuador: the
      causative Leishmania parasites and clinico-epidemiological features.
AB  - This study provides comprehensive information on the past and current status of
      the Andean cutaneous leishmaniasis (Andean-CL, uta) in Peru and Ecuador, mainly
      focusing on the causative Leishmania parasites and clinico-epidemiological
      features. Available information and data including our unpublished works were
      analyzed thoroughly. Endemic regions of the Andean-CL (uta) in Peru run from the
      north Piura/Cajamarca to the south Ayacucho at a wide range of the Pacific
      watersheds of the Andes through several departments, while in Ecuador those exist
      at limited and spotted areas in the country's mid-southwestern two provinces,
      Azuay and Chimborazo. The principal species of the genus Leishmania are
      completely different at subgenus level, L. (Viannia) peruviana in Peru, and L.
      (Leishmania) mexicana and L. (L.) major-like (infrequent occurrence) in Ecuador.
      The Peruvian uta is now prevalent in different age and sex groups, being not
      clearly defined as found in the past. The precise reasons are not known and
      should be elucidated further, though probable factors, such as emergence of other
      Leishmania parasites, non-immune peoples' migration into the areas, etc., were
      discussed briefly in the text. The Andean-CL cases in Ecuador are more rural than
      before, probably because of a rapid development of the Leishmania-positive
      communities and towns, and the change of life-styles of the inhabitants,
      including newly constructed houses and roads in the endemic areas. Such
      information is helpful for future management of the disease, not only for
      Leishmania-endemic areas in the Andes but also for other endemic areas.

PMID- 29017879
TI  - Preparation of poly(lactide)/lignin/silver nanoparticles composite films with UV
      light barrier and antibacterial properties.
AB  - Organosolv lignin was used as a reducing agent for the preparation of silver
      nanoparticles (AgNPs) and their incorporation into poly(lactide) (PLA) polymer to
      prepare composite films. The composite films were characterized using UV-vis
      spectroscopy, FE-SEM, FTIR, XRD, and TGA. The optical, mechanical, water vapor
      barrier, and antibacterial properties of the composite films were evaluated. The
      UV-vis spectra of films exhibited two characteristics peaks around 300 and 450nm
      attributed to lignin and AgNPs, respectively. XRD results indicated that the
      crystalline AgNPs had been formed. The transmission of light at 280nm decreased
      significantly after incorporation of lignin and AgNPs. FTIR results showed that
      there was no change in the chemical structure of PLA after incorporation of
      lignin and AgNPs. The mechanical and water vapor barrier properties of the
      composite films increased after lignin and AgNPs incorporation, The films
      containing AgNPs exhibited potent antibacterial activity against Escherichia coli
      and Listeria monocytogenes.

PMID- 29017880
TI  - Development, physicochemical characterization and cytotoxicity of selenium
      nanoparticles stabilized by beta-lactoglobulin.
AB  - Novel Selenium nanoparticles (SeNPs) were developed using beta-lactoglobulin
      (Blg) as a stabilizer in redox systems of selenite and ascorbic acid in this
      study. Particle size, morphology, stability, and in vitro biological activity of
      synthesized Blg stabilized selenium nanoparticles (Blg-SeNPs) were characterized
      by dynamic light scattering (DLS), transmission electron microscopy (TEM),
      ultraviolet-visible spectrophotometry (UV/Vis), and cell toxicity assays,
      respectively. Stabilizing mechanisms of Blg-SeNPs were investigated by Fourier
      transform infrared spectroscopy (FTIR) and protein fluorescence probe. The
      results revealed that the Blg-SeNPs were spherical with mean particle size of
      36.8+/-4.1nm. They were stable in acidic or neutral to basic solutions (pH 2.5
      3.5 or 6.5-8.5) at 4 degrees C for 30days as a result of electrostatic
      repulsions. FTIR results showed that functional groups of NH2 and OH on Blg
      molecules were responsible for binding with SeNPs. Furthermore, decreases in
      protein surface hydrophobicity indicated that possible binding happened between
      Se and the hydrophobic domains of Blg. The cell toxicity of Blg-SeNPs was
      significantly lower than that of sodium selenite on both cancerous and non
      cancerous cells. This study provides a facile and green method for chemically
      synthesizing stable SeNPs which are suitable for further evaluation in medicinal
      applications.

PMID- 29017881
TI  - The effects of allantoin, arginine and NaCl on thermal melting and aggregation of
      ribonuclease, bovine serum albumin and lysozyme.
AB  - Allantoin is widely used as a skin care agent and readily forms crystals, which
      were recently shown to bind endotoxins and high molecular weight aggregates in
      cell culture harvests. Here, we have investigated the effects of allantoin on
      thermal stability and aggregation of protein using ribonuclease, bovine serum
      albumin and lysozyme using temperature-regulated circular dichroism (CD) and
      differential scanning microcalorimetry (DSC). Ribonuclease showed no change in
      thermal stability and aggregation by the addition of allantoin. While allantoin
      showed no effects on the thermal stability of bovine serum albumin, it enhanced
      aggregation. Similarly, allantoin showed no stabilizing effects on lysozyme, but
      it strongly suppressed aggregation. Such suppressed aggregation resulted in
      reversibility of thermal unfolding of lysozyme. These effects of allantoin were
      then compared with those of NaCl and arginine hydrochloride. Arginine was similar
      to allantoin at low concentrations, where both solvent additives can be compared
      due to limited solubility of allantoin.

PMID- 29017882
TI  - Enzymatic purification and structure characterization of glucuronoxylan from
      water extract of Cassia obtusifolia seeds.
AB  - Enzymatic hydrolysis was proposed for the first time to purify the sub-fraction
      of water-extracted cassia polysaccharide (CP-40), and a homogeneous
      polysaccharide CP-40-M was obtained with relatively high yield. The structural
      features of CP-40-M were characterized using size-exclusion chromatography
      equipped with multiple detectors (SEC-MALLS), high-performance anion-exchange
      chromatography (HPAEC), methylation and gas chromatography-mass (GC-MS), as well
      as nuclear magnetic resonance (NMR) spectra. The weight-average molecular weight
      for CP-40-M was determined to be 0.29*105Da, and the molar ratio of xylose to
      glucuronic acid was 4.62. The structure of CP-40-M was elucidated to be
      glucuronoxylan, with glucopyranosyluronic acid group terminally attached to O-2
      of the ->4)-beta-Xylp-(1-> backbone. It was the first time to obtain this type of
      xylan from the water extract of Cassia obtusifolia seeds. The structure
      elucidation of CP-40-M was meaningful for better understanding the natural
      characteristics of cassia polysaccharide and important for their potential use in
      food industry and folk medicine.

PMID- 29017883
TI  - Effect of salt on the coil-helix transition of gelatin at early stages: Optical
      rotation, rheology and DSC studies.
AB  - The influence of the concentration and type of salt on the physical gelation of
      gelatin at early stages was explored by polarimeter, rheometer and differential
      scanning calorimetry (DSC). With the increase of salt concentration, both the
      triple helix content and the storage modulus of gelatin increased slightly and
      then decreased in CaCl2 solutions, whereas they decreased monotonically in NaCl
      and CrCl3 solutions. The addition of CaCl2 at low concentrations facilitated the
      coil-helix transition of gelatin, which could be significantly inhibited by high
      salt concentrations. The melting temperature of gels was nearly unchanged with
      varying salt concentration, but the melting enthalpy decreased monotonically with
      salt addition. This result indicates that salt additions mainly affect the
      nucleation of triple helices, but had minor effect on its growth. In addition,
      the coil-helix transition of gelatin in salt solutions at early stages could be
      treated successfully by an equation of first order kinetics.

PMID- 29017884
TI  - Molecular and immunological toxic effects of nanoparticles.
AB  - Nanoparticles have emerged as a boon for the public health applications such as
      drug delivery, diagnostic, and imaging. Biodegradable and non-bio degradable
      nanoparticles have been used at a large scale level to increase the efficiency of
      the biomedical process at the cellular, animal and human level. Exponential use
      of nanoparticles reinforces the adverse immunological changes at the human health
      level. Physical and chemical properties of nanoparticles often lead to a variety
      of immunotoxic effects such as activation of stress-related genes, membrane
      disruption, and release of pro-inflammatory cytokines. Delivered nanoparticles in
      animal or human interact with various components of the immune system such as
      lymphocytes, macrophages, neutrophils etc. Nanoparticles delivered above the
      threshold level damages the cellular physiology by the generation of reactive
      oxygen and nitrogen species. This review article represents the potential of
      nanoparticles in the field of nanomedicine and provides the critical evidence
      which leads to develop immunotoxicity in living cells and organisms by altering
      immunological responses.

PMID- 29017885
TI  - Simplified approach for in-vitro production and purification of cell derived
      Cancer Antigen 15-3.
AB  - Cancer antigen 15-3 (CA15-3) is a key biomarker, currently used for understanding
      the onset and prognosis of breast cancer. In present investigation, CA15-3 has
      been purified from the culture supernatant of breast cancer T47-D cell line with
      76% yield and 3350 fold purification. Isolated CA15-3 was analyzed by sodium
      dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting
      (western blotting), chemiluminescence immunoassay (CLIA) and Fourier-transform
      infrared spectroscopy (FTIR). CA15-3 is a monomeric protein with an apparent
      molecular mass in between ~250-350kDa. The FTIR spectroscopy revealed similar
      profiles of T47-D derived CA15-3 and commercially available CA15-3 protein. With
      the easy availability of T47-D cell line and a simple purification approach
      described here will support for the large scale production of CA15-3 to be used
      for various clinical and diagnostic applications.

PMID- 29017886
TI  - Complex coacervation between lysozyme and pectin: Effect of pH, salt, and
      biopolymer ratio.
AB  - The complexation between lysozyme and pectin was studied by acidification using
      zeta potential, turbidity measurements and calorimetry titration. The complexes
      were analyzed in various NaCl concentrations with different ratios. At ratio 1:1
      with 0.01M NaCl, is worth mentioning that the insoluble complexes were formed
      between pH 2.0 and 7.0, which represents a great range to apply this complex to
      different food matrices. When the ratio was increased from 1:1 to 3:1, the pH
      range between the pHphi1 and pHphi2 increased even more. When the NaCl
      concentration was increased from 0.01M to 0.2M, a progressive reduction of
      turbidity was observed. At 0.4M NaCl, there was total suppression of complex
      formation at ratio <= 3:1. The process of complex coacervate formation occurred
      in two different steps, presenting favorable enthalpic as well as entropic
      contributions. The positive entropy change is a strong indication that water
      molecules have been released from the complex surface, however the positive sign
      of TDeltaS suggests that hydrophobic interactions were involved in the
      interaction between lysozyme and pectin. Microscopy images of the samples
      revealed that the complexes presented a spheroid-like appearance which may
      contribute to possible future applications.

PMID- 29017887
TI  - Functional properties and utilization of Artocarpus heterophyllus Lam seed starch
      from new species in China.
AB  - Jackfruit is now receiving extensive attention as a new source of starch.
      However, jackfruit seeds are discarded as waste, although they are rich in
      starch. The functional properties of the starches were investigated from new
      Chinese jackfruit species. All the starches have a high amylose (26.56-38.34%)
      with a potential to become functional foods rich in resistant starch. The
      jackfruit starches varied from trigonal and tetragonal, round to semi-oval/bell
      shapes and showed significant variations in particle sizes (5.53-14.46MUm). These
      variations led to significant differences in their functional properties, and
      significant correlations were found in their pasting, thermal, crystal and
      texture parameters. Hierarchical cluster analysis sorted the samples into three
      groups of 1) Malaysia 8 (M8) and ZhenZhu (ZZ); 2) Malaysia 2, Malaysia 3 and
      Malaysia 4, (M2, M3, M4); and 3) Xiangyinsuo 11, Xiangyinsuo 4, Xiangyinsuo 3 and
      Xiangyinsuo 2 (X11, X4, X3, X2). The first group could be used as food thickening
      or gelling agents. The second group could be applied in glutinous foods. The
      third group make them suitable for fillings in confectionery or weaning foods.

PMID- 29017888
TI  - Impact of amikacin pharmacokinetic/pharmacodynamic index on treatment response in
      critically ill patients.
AB  - OBJECTIVES: This study evaluated the association between the
      pharmacokinetic/pharmacodynamic index and treatment response to amikacin in
      critically ill patients. METHODS: An observational prospective study was
      designed. Critically ill adult patients with infection due to amikacin-sensitive
      Gram-negative bacteria treated with amikacin were included. Amikacin maximum
      (Cmax) and minimum (Cmin) plasma concentration samples were taken during the
      first 48-96h after the beginning of treatment. The impact of Cmax/MIC ratio and
      area under the concentration-time curve (AUC)/MIC ratio on early and final
      clinical response, microbiological eradication, development of resistant strains
      and renal toxicity was analysed using a multivariate model. RESULTS: A total of
      85 patients received amikacin treatment, of whom 71 (83.5%) achieved a Cmax/MIC
      >6, 66 (77.6%) a Cmax/MIC >8, 64 (75.3%) a Cmax/MIC >10 and 72 (84.7%) an AUC/MIC
      >65. Clinical response at the end of treatment was significantly greater in
      patients with Cmax/MIC >6 [OR=5.48 (95% CI 1.28-11.40)], Cmax/MIC >8 [OR=6.01
      (2.41-12.2)] and Cmax/MIC >10 [OR=8.02 (2.21-14.2)]. Cmax/MIC >10 was associated
      with a non-significant increase in microbiological eradication [OR=2.84 (0.76
      10.61)]. Achieving Cmax/MIC >6 was associated with a lower proportion of patients
      with selection of resistant strains or with an increase in amikacin MIC (27.8%
      vs. 10.2%). Amikacin AUC was associated with development of nephrotoxicity [ROC
      curve 0.77 (0.66-0.87)]. CONCLUSIONS: The Cmax/MIC ratio of amikacin in
      critically ill patients is directly related to the response to treatment and the
      selection of resistant strains.

PMID- 29017889
TI  - Complete genome sequence of Acinetobacter baumannii A1296 (ST1469) with a small
      plasmid harbouring the tet(39) tetracycline resistance gene.
AB  - OBJECTIVES: Acinetobacter baumannii is considered an important nosocomial
      pathogen worldwide owing to its increasing antibiotic resistance. This study
      aimed to determine the complete genome sequence of A. baumannii strain A1296 and
      to perform a comparative analysis among A. baumannii. METHODS: The complete
      genome sequence of A. baumannii A1296 was sequenced on two SMRT cells using P6C4
      chemistry on a PacBio Single Molecule, Real-Time (SMRT) RS II instrument. The
      A1296 genome sequence was annotated using Prokaryotic Genome Automatic Annotation
      Pipeline (PGAAP), and the sequence type and resistance genes of the strain were
      analysed. RESULTS: Here we present the complete genome sequence of A. baumannii
      strain A1296, belonging to a novel sequence type (ST1469) and isolated from
      patient in China, that was sensitive to multiple antibiotics. The genome of A.
      baumannii A1296 was 3810701bp in length, including one circular chromosome and
      two plasmids. The tet(39) resistance gene was located on the small plasmid in
      this A. baumannii strain. CONCLUSIONS: The genome sequence of A. baumannii strain
      A1296 can be used as a reference sequence for comparative analysis aimed at
      elucidating the acquisition, dissemination and mobilisation of resistance genes
      among A. baumannii.

PMID- 29017890
TI  - Faulty BRCA1, BRCA2 genes: how poor is the prognosis?
AB  - We take a critical look at the meaning behind the number 87% given to 25-year-old
      Sophie, a BRCA1 and BRCA2 carrier. Sophie has been told she has an 87% chance of
      getting breast cancer. She is contemplating a preventive double mastectomy after
      genetic counseling and her physician's advice. Some 92% of British general
      practitioners are in favor of prophylactic mastectomy as a treatment option for
      women similar to Sophie. The treatment decision results, to a very large extent,
      from the size of the number (87%) alone. The central argument of this study is
      that physicians, their patients, and the public need a much better understanding
      on what is meant by probability estimates of 0.87. The figure on its own does not
      tell us much, and we need to be very cautious in its interpretation. It is
      important to know that the very same genetic and statistical models, and observed
      data, resulting in a verdict of an 87% lifetime chance of getting breast cancer,
      based on BRCA1, BRCA2, and familial information, simultaneously show Sophie to
      have a greater than 99% chance of surviving beyond the next 5 years cancer free.
      If she succeeds-the chances are overwhelmingly in her favor-then, given that
      fact, her chances of surviving a further 5 years are once again greater than 98%.
      Her chances of not dying due to breast cancer over the next 20 years are greater
      than 97%, a percentage that changes little if instead of 20 we write the number
      30. In a word, although the diagnosis of a faulty BRAC gene may be a
      disappointment, there is no immediate peril and no need for undue alarm. Sophie,
      and her primary care providers, can carefully consider her options without
      feeling that they are under any kind of acute pressure. Whatever the threat, it
      is not an imminent one.

PMID- 29017891
TI  - A pilot study of an accelerometer-equipped smartphone to monitor older adults
      with cancer receiving chemotherapy in Mexico.
AB  - OBJECTIVES: Older adults with cancer in developing countries face challenges
      accessing healthcare due to a lack of personnel and infrastructure. A decline in
      physical activity (defined as a decrease in the number of daily steps) may be a
      novel method for the timely detection of toxicity in older adults receiving
      chemotherapy in resource-constrained settings. MATERIALS AND METHODS: In this
      feasibility study, patients aged >=65years starting first-line chemotherapy for
      solid tumors were given a smartphone with a pedometer application. Daily steps
      were monitored daily for one cycle. If a >=15% decrease from baseline was
      identified, the patient was called and the presence of toxicity assessed. The
      intervention would be feasible if >=75% of the subjects recorded steps for >=75%
      of the planned chemotherapy days. RESULTS: Forty patients (median age 73; 57%
      [N=23] female) were included. Seventy percent (N=28) had stage III-IV disease
      with 45% (N=18) gastrointestinal, 23% (N=9) breast, and 32% (N=13) other
      malignancies. Mean pre-treatment daily steps was 3111 (Standard Deviation [SD]
      1731), and median follow-up was 21days (range 2-28). Despite having limited
      exposure to mobile technology, most (93%) patients used the smartphone
      appropriately, and 85% found it easy to use. Sixty percent of patients (N=24) had
      toxicities managed over the phone, 27.5% (N=10) were sent for urgent medical
      attention and 15% (N=6) were hospitalized. CONCLUSION: Using smartphones to
      monitor older adults with cancer receiving chemotherapy in a resource-constrained
      setting is feasible and acceptable. A decrease in the number of daily steps was
      common and helped to identify chemotherapy toxicity.

PMID- 29017892
TI  - Muscle functions and bone strength are impaired in adolescents with type 1
      diabetes.
AB  - BACKGROUND: Sarcopenia and osteoporosis are among the late complications of type
      1 diabetes (T1D) in adults. Whether and to what extent musculoskeletal impairment
      is present in childhood and adolescence has yet to be determined. The aim of this
      study was to assess volumetric bone mineral density (BMD) and dynamic muscle
      function in adolescents with T1D and to assess the clinical and biochemical
      predictors of their musculoskeletal system. METHODS: Ninety-five children and
      adolescents (59 boys and 36 girls, mean age 16.2+/-1.2years) with T1D were
      included in this cross-sectional study. Study participants were divided into two
      groups according to the duration of the disease (<6years and >9years,
      respectively). Volumetric BMD of the non-dominant tibia was assessed using
      peripheral quantitative computed tomography (pQCT). Dynamic muscle function was
      evaluated using jumping mechanography. Gender- and height-specific Z-scores were
      calculated using published reference data. HbA1c was evaluated retrospectively as
      an average over the past 5years. RESULTS: Relative muscle power (Pmax/mass) and
      force (Fmax/body weight) were significantly decreased in T1D subjects (mean Z
      scores -0.4+/-1.0; p<0.001, and -0.3+/-1.1; p<0.01, respectively). The duration
      of T1D negatively affected Pmax/mass (p<0.01) but not Fmax/body weight (p=0.54).
      Patients with T1D had also decreased trabecular BMD, the Strength-Strain Index
      and cortical thickness (mean Z-scores -0.8+/-1.3; -0.5+/-0.8 and -1.1+/-0.8,
      respectively, p<0.001 for all) whereas cortical BMD was increased when compared
      to controls (Z-score 1.2+/-0.90, p<0.001). No association was observed between
      the HbA1c and 25-hydroxyvitamin D levels and bone or muscle parameters.
      CONCLUSION: T1D influences the musculoskeletal system in adolescence. Decreased
      muscle function could contribute to the osteoporosis reported in adult diabetic
      patients.

PMID- 29017894
TI  - Rotavirus-encoded virus-like small RNA triggers autophagy by targeting IGF1R via
      the PI3K/Akt/mTOR pathway.
AB  - Rotaviruses are double-stranded RNA viruses that are a major cause of viral
      diarrhea in infants. Examining virus-host cell interaction is important for
      elucidating mechanisms of virus proliferation in host cells. Viruses can create
      an environment that promotes their survival and self-proliferation by encoding
      miRNAs or miRNA-like molecules that target various host cell. However, it remains
      unclear whether RNA viruses encode viral miRNAs, and their regulation mechanisms
      are largely unknown. We previously performed deep sequencing analysis to
      investigate rotavirus-encoded miRNAs, and identified the small RNA molecule
      Chr17_1755, which we named RV-vsRNA1755. In our present study, we determined that
      RV-vsRNA1755 is encoded by the rotavirus NSP4 gene and that it targets the host
      cell IGF1R, which is part of the PI3K/Akt pathway. We further explored the
      biological characteristics and functions of RV-vsRNA1755.Our results suggest that
      rotavirus adapts to manipulate PI3K/Akt signaling at early phases of infection.
      RV-vsRNA1755 targets IGF1R, blockading the PI3K/Akt pathway and triggering
      autophagy, but it ultimately inhibits autophagy maturation. A mechanism through
      which rotavirus encodes a virus-like small RNA (RV-vsRNA1755) that triggers
      autophagy by targeting the host cell IGF1R gene was revealed. These data provide
      a theoretical basis for therapeutic drug screening targeting RV-vsRNA1755.

PMID- 29017896
TI  - MG53 and disordered metabolism in striated muscle.
AB  - MG53 is a member of tripartite motif family (TRIM) that expressed most abundantly
      in striated muscle. Using rodent models, many studies have demonstrated the MG53
      not only facilitates membrane repair after ischemia reperfusion injury, but also
      contributes to the protective effects of both pre- and post-conditioning.
      Recently, however, it has been shown that MG53 participates in the regulation of
      many metabolic processes, especially insulin signaling pathway. Thus, sustained
      overexpression of MG53 may contribute to the development of various metabolic
      disorders in striated muscle. In this review, using cardiac muscle as an example,
      we will discuss muscle metabolic disturbances associated with diabetes and the
      current understanding of the underlying molecular mechanisms; in particular, the
      pathogenesis of diabetic cardiomyopathy. We will focus on the pathways that MG53
      regulates and how the dysregulation of MG53 leads to metabolic disorders, thereby
      establishing a causal relationship between sustained upregulation of MG53 and the
      development of muscle insulin resistance and metabolic disorders. This article is
      part of a Special issue entitled Cardiac adaptations to obesity, diabetes and
      insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and
      Christine Des Rosiers.

PMID- 29017893
TI  - Chronic inflammation - inflammaging - in the ageing cochlea: A novel target for
      future presbycusis therapy.
AB  - Chronic, low-grade inflammation, or inflammaging, is a crucial contributor to
      various age-related pathologies and natural processes in aging tissue, including
      the nervous system. Over the past two decades, much effort has been done to
      understand the mechanisms of inflammaging in disease models such as type II
      diabetes, cardiovascular disease, Alzheimer's disease, Parkinson's disease, and
      others. However, despite being the most prevalent neurodegenerative disorder, the
      number one communication disorder, and one of the top three chronic medical
      conditions of our aged population; little research has been conducted on the
      potential role of inflammation in age-related hearing loss (ARHL). Recently, it
      has been suggested that there is an inflammatory presence in the cochlea, perhaps
      involving diffusion processes of the blood-brain barrier as it relates to the
      inner ear. Recent research has found correlations between hearing loss and
      markers such as C-reactive protein, IL-6, and TNF-alpha indicating inflammatory
      status in human case-cohort studies. However, there have been very few reports of
      in vivo research investigating the role of chronic inflammation's in hearing loss
      in the aging cochlea. Future research directed at better understanding the
      mechanisms of inflammation in the cochlea as well as the natural changes acquired
      with aging may provide a better understanding of how this process can accelerate
      presbycusis. Animal model experimentation and pre-clinical studies designed to
      recognize and characterize cochlear inflammatory mechanisms may suggest novel
      treatment strategies for preventing or treating ARHL. In this review, we seek to
      summarize key research in chronic inflammation, discuss its implications for
      possible roles in ARHL, and finally suggest directions for future investigations.

PMID- 29017897
TI  - Patients' Conceptions of Terms Related to Sexual Interest, Desire, and Arousal.
AB  - BACKGROUND: Measurement of sexual function typically uses self-report, which, to
      work as intended, must use language that is understood consistently by diverse
      respondents. Commonly used measures employ multiple terms, primarily (sexual)
      interest, desire, and arousal, that might not be understood in the same way by
      laypeople and professionals. AIM: To inform self-reported measurement efforts for
      research and clinical settings by examining how US men and women recruited from a
      health care setting understand and interpret different terms. METHODS: We
      conducted 10 focus groups in Durham, NC (N = 57). Discussions were audio-recorded
      and transcribed, and the content of the discussions was systematically analyzed
      in 2 phases of coding by the research team, facilitated by Nvivo qualitative
      analysis software (QSR International, Doncaster, VIC, Australia). OUTCOMES:
      Patient focus group discussions about the meanings and connotations of multiple
      terms related to sexual function, especially interest, desire, and arousal.
      RESULTS: 5 groups included male participants and 5 included female participants.
      Participants characterized (sexual) interest as a cognitive phenomenon and a
      situational response to a specific person. Similarly, they characterized (sexual)
      desire as a situational person-specific experience with some support for it as a
      cognitive phenomenon but more support for it as a physical phenomenon. In
      contrast, participants characterized sexual arousal as a physical phenomenon
      occurring in response to physical or visual stimulation and not related to a
      specific person. CLINICAL IMPLICATIONS: These results can help us understand how
      laypeople are using and responding to these terms when they are used in clinical
      and research settings. STRENGTHS AND LIMITATIONS: Patient participants in these
      groups were diverse in age, gender, sexual orientation, and health, with the
      potential to voice diverse perspectives on sexual functioning; however, the
      sample was limited to a single city in the southeastern United States.
      CONCLUSION: The meanings of interest, desire, and arousal were defined, compared,
      and contrasted in the context of patient focus groups. Qualitative coding showed
      that interest was considered the most "cognitive," arousal the most "physical,"
      and desire somewhere in between. DeLamater JD, Weinfurt KP, Flynn KE. Patients'
      Conceptions of Terms Related to Sexual Interest, Desire, and Arousal. J Sex Med
      2017;14:1327-1335.

PMID- 29017898
TI  - A hierarchical structure for human behavior classification using STN local field
      potentials.
AB  - BACKGROUND: Classification of human behavior from brain signals has potential
      application in developing closed-loop deep brain stimulation (DBS) systems. This
      paper presents a human behavior classification using local field potential (LFP)
      signals recorded from subthalamic nuclei (STN). METHOD: A hierarchical
      classification structure is developed to perform the behavior classification from
      LFP signals through a multi-level framework (coarse to fine). At each level, the
      time-frequency representations of all six signals from the DBS leads are combined
      through an MKL-based SVM classifier to classify five tasks (speech, finger
      movement, mouth movement, arm movement, and random segments). To lower the
      computational cost, we alternatively use the inter-hemispheric synchronization of
      the LFPs to make three pairs out of six bipolar signals. Three classifiers are
      separately trained at each level of the hierarchical approach, which lead to
      three labels. A fusion function is then developed to combine these three labels
      and determine the label of the corresponding trial. RESULTS: Using all six LFPs
      with the proposed hierarchical approach improves the classification performance.
      Moreover, the synchronization-based method reduces the computational burden
      considerably while the classification performance remains relatively unchanged.
      COMPARISON WITH EXISTING METHODS: Our experiments on two different datasets
      recorded from nine subjects undergoing DBS surgery show that the proposed
      approaches remarkably outperform other methods for behavior classification based
      on LFP signals. CONCLUSION: The LFP signals acquired from STNs contain useful
      information for recognizing human behavior. This can be a precursor for designing
      the next generation of closed-loop DBS systems.

PMID- 29017899
TI  - A brain-computer interface based on functional transcranial doppler ultrasound
      using wavelet transform and support vector machines.
AB  - BACKGROUND: Functional transcranial Doppler (fTCD) is an ultrasound based
      neuroimaging technique used to assess neural activation that occurs during a
      cognitive task through measuring velocity of cerebral blood flow. NEW METHOD: The
      objective of this paper is to investigate the feasibility of a 2-class and 3
      class real-time BCI based on blood flow velocity in left and right middle
      cerebral arteries in response to mental rotation and word generation tasks.
      Statistical features based on a five-level wavelet decomposition were extracted
      from the fTCD signals. The Wilcoxon test and support vector machines (SVM), with
      a linear kernel, were employed for feature reduction and classification. RESULTS:
      The experimental results showed that within approximately 3s of the onset of the
      cognitive task average accuracies of 80.29%, and 82.35% were obtained for the
      mental rotation versus resting state and the word generation versus resting state
      respectively. The mental rotation task versus word generation task achieved an
      average accuracy of 79.72% within 2.24s from the onset of the cognitive task.
      Furthermore, an average accuracy of 65.27% was obtained for the 3-class problem
      within 4.68s. COMPARISON WITH EXISTING METHODS: The results presented here
      provide significant improvement compared to the relevant fTCD-based systems
      presented in literature in terms of accuracy and speed. Specifically, the
      reported speed in this manuscript is at least 12 and 2.5 times faster than any
      existing binary and 3-class fTCD-based BCIs, respectively. CONCLUSIONS: These
      results show fTCD as a promising and viable candidate to be used towards
      developing a real-time BCI.

PMID- 29017895
TI  - Short-term fructose ingestion affects the brain independently from establishment
      of metabolic syndrome.
AB  - Chronic fructose ingestion is linked to the global epidemic of metabolic syndrome
      (MetS), and poses a serious threat to brain function. We asked whether a short
      period (one week) of fructose ingestion potentially insufficient to establish
      peripheral metabolic disorder could impact brain function. We report that the
      fructose treatment had no effect on liver/body weight ratio, weight gain, glucose
      tolerance and insulin sensitivity, was sufficient to reduce several aspects of
      hippocampal plasticity. Fructose consumption reduced the levels of the neuronal
      nuclear protein NeuN, Myelin Basic Protein, and the axonal growth-associated
      protein 43, concomitant with a decline in hippocampal weight. A reduction in
      peroxisome proliferator-activated receptor gamma coactivator-1 alpha and
      Cytochrome c oxidase subunit II by fructose treatment is indicative of
      mitochondrial dysfunction. Furthermore, the GLUT5 fructose transporter was
      increased in the hippocampus after fructose ingestion suggesting that fructose
      may facilitate its own transport to brain. Fructose elevated levels of
      ketohexokinase in the liver but did not affect SIRT1 levels, suggesting that
      fructose is metabolized in the liver, without severely affecting liver function
      commensurable to an absence of metabolic syndrome condition. These results
      advocate that a short period of fructose can influence brain plasticity without a
      major peripheral metabolic dysfunction.

PMID- 29017900
TI  - Neural electrode resilience against dielectric damage may be improved by use of
      highly doped silicon as a conductive material.
AB  - BACKGROUND: Dielectric damage occurring in vivo to neural electrodes, leading to
      conductive material exposure and impedance reduction over time, limits the
      functional lifetime and clinical viability of neuroprosthetics. We used silicon
      micromachined Utah Electrode Arrays (UEAs) with iridium oxide (IrOx) tip
      metallization and parylene C dielectric encapsulation to understand the factors
      affecting device resilience and drive improvements. NEW METHOD: In vitro
      impedance measurements and finite element analyses were conducted to evaluate how
      exposed surface area of silicon and IrOx affect UEA properties. Through an
      aggressive in vitro reactive accelerated aging (RAA) protocol, in vivo parylene
      degradation was simulated on UEAs to explore agreement with our models.
      Electrochemical properties of silicon and other common electrode materials were
      compared to help inform material choice in future neural electrode designs.
      RESULTS: Exposure of silicon on UEAs was found to primarily affect impedance at
      frequencies >1kHz, while characteristics at 1 kHz and below were largely
      unchanged. Post-RAA impedance reduction of UEAs was mitigated in cases where
      dielectric damage was more likely to expose silicon instead of IrOx. Silicon was
      found to have a per-area electrochemical impedance >10*higher than many common
      electrode materials regardless of doping level and resistivity, making it best
      suited for use as a low-shunting conductor. COMPARISON WITH EXISTING METHODS: Non
      semiconductor electrode materials commonly used in neural electrode design are
      more susceptible to shunting neural interface signals through dielectric defects,
      compared to highly doped silicon. CONCLUSION: Strategic use of silicon and
      similar materials may increase neural electrode robustness against encapsulation
      failures.

PMID- 29017901
TI  - Immediate reactions to iodinated contrast media.
AB  - BACKGROUND: Immediate hypersensitivity reactions (IHRs) to iodinated contrast
      media (ICMs) remain a common clinical concern. Positive skin test and basophil
      activation test results suggest a specific IgE-mediated mechanism in some cases.
      Skin test and controlled challenge test (CCT) are useful to manage these
      patients. OBJECTIVE: To study clinical and allergologic features of IHRs to ICMs
      in a Spanish tertiary hospital during a 7-year period. METHODS: Demographic and
      clinical data concerning the reaction were recorded. Patients treated at the
      Allergy Department of Hospital General Universitario Gregorio Maranon, Madrid,
      Spain, underwent skin tests. In those with positive results, CCTs with an
      alternative skin-test-negative ICM was performed. Global reaction rate was
      calculated and compared for each ICM. RESULTS: A total of 342 reactions occurred
      in 329 patients. Cutaneous symptoms were the most common (87.7%). A total of 196
      patients underwent an allergy workup, 15 (7.6%) of whom had positive skin test
      results. Reactions were more severe in patients with positive vs negative skin
      test results (grade 1, 46.7% vs 73.6%; grade 2, 33.3% vs 20.9%; grade 3, 20% vs
      5.46%; P < .05). Three patients had cross-reactivity to 3 ICMs, all including
      ioversol and iomeprol. Six patients allergic to iopamidol tolerated ioversol and
      1 tolerated iomeprol. Four patients allergic to ioversol and 1 allergic to
      iomeprol tolerated iopamidol. The global reaction rate was 0.2%, differing for
      each ICM (iopamidol, 0.14%; ioversol, 0.2%; and iomeprol, 0.4%; P < .001).
      Positive skin test results were found in a low percentage of patients in whom
      skin test-based CCT identified an alternative non-cross-reactive ICM. Low-grade
      cross-reactivity was found, especially between iopamidol and ioversol. Reactions
      were more severe in patients with positive skin test results. The reaction rate
      was greater for iomeprol compared with iopamidol (reaction rate, 2.8%) and
      ioversol (reaction rate, 2%). CONCLUSION: This study identified a possible
      underlying specific IgE-mediated mechanism by positive skin test result in a low
      percentage of patients with IHRs to ICMs. In these patients, the CCT based on
      skin test results was useful for identifying an alternative non-cross-reactive
      ICM. More studies are needed to investigate the underlying mechanism in patients
      with IHRs and negative skin test results.

PMID- 29017902
TI  - Small percentage of anaphylactic reactions treated with epinephrine during food
      challenges in Dutch children.
AB  - BACKGROUND: Severe allergic reactions, including anaphylaxis, occur during oral
      food challenges (OFCs) and the first-line treatment of anaphylaxis is
      epinephrine. OBJECTIVE: To evaluate the percentage of anaphylactic reactions
      treated with epinephrine during OFCs and to identify associated factors for the
      administration of epinephrine. METHODS: Children who underwent an OFC with
      peanut, hazelnut, cow's milk, hen's egg, or cashew nut from 2005 through 2015 in
      the Netherlands were evaluated. Children with reactions meeting the criteria for
      anaphylaxis according to the European Academy of Allergy and Clinical Immunology
      guidelines for food allergy and anaphylaxis were included. Children with an
      anaphylactic reaction treated with vs without epinephrine were compared. Possible
      factors associated with the administration of epinephrine, such as age, sex,
      symptoms consistent with asthma, history of an allergic reaction to the tested
      allergen, and symptom types during the anaphylactic reaction, were evaluated
      using logistic regression analysis. RESULTS: Eighty-three children in clinical
      and research settings (43% boys; median age, 7 years; range, 1-17) who met the
      criteria for anaphylaxis were included in this study. Thirty-two of 83 children
      (39%) with anaphylaxis were treated with epinephrine. Respiratory symptoms during
      the OFC were treated significantly more often with epinephrine than
      gastrointestinal symptoms (P = .01). CONCLUSION: Only 39% of children with
      anaphylaxis, according to the guideline criteria, were treated with epinephrine
      during the OFC and most of these children had respiratory symptoms. There is need
      for an easy-to-use international guideline for the treatment of allergic symptoms
      during OFCs.

PMID- 29017903
TI  - Successful perinatal management of hereditary angioedema with normal C1 esterase
      inhibitor and factor XII mutation using C1 esterase inhibitor therapy.

PMID- 29017904
TI  - Spicing up your advice for South Asian and Anglo-Australians with type 2 diabetes
      and CVD: Do cultural constructions of diet matter?
AB  - South Asians are a growing migrant population, both globally and in Australia.
      This group are at higher risk for both cardiovascular disease and type 2
      diabetes. The aim of this qualitative study was to compare dietary practices of
      South Asians, n = 41 (Indian, n = 25; Sri Lankan, n = 16) and Anglo-Australians,
      n = 16, with these conditions, using semi-structured in-depth interviews.
      Findings suggest that both groups had a high level of awareness of dietary
      practices necessary for optimum disease management, both prior to and post
      diagnosis. Bi-directional effects of migration were noted in the dietary
      practices of both groups suggesting hybrid diets are evident in Australia. A key
      barrier to implementing dietary changes highlighted by both groups of
      participants was a lack of specific, timely and detailed dietary advice from
      clinicians. Both groups expressed that advice should be repeated and reinforced
      throughout the course of their disease. In addition, South Asian participants
      wanted more culturally relevant advice. Clinicians providing dietary advice need
      to recognise that preferences for staple food items are resistant to change and
      may affect adherence. Acculturation was evident in the dietary practices of the
      South Asian participants. Nevertheless, many maintained traditional food
      practices which were tied to their cultural identity. It is recommended that
      clinicians consider these factors when offering advice.

PMID- 29017905
TI  - Evaluation of a pilot sensory play intervention to increase fruit acceptance in
      preschool children.
AB  - Recent research has found an association between dislike of messy play and higher
      levels of food neophobia in children. The aim of the present study was to pilot
      and assess a five week intervention with preschool children, to examine whether
      engagement in tactile sensory tasks leads to increased fruit acceptance.
      Interventions were carried out to examine whether weekly sessions of sensory play
      combined with fruit exposure, would increase acceptance and enjoyment of fruits
      to a greater extent than two non-sensory play conditions featuring fruit exposure
      or normal play activities alone. One hundred children aged 18 months to four
      years were recruited from ten playgroups in the Midlands area of the United
      Kingdom (UK) of which 83 completed the interventions. Participants were randomly
      assigned to one of four conditions: combined sensory play (fruit and non-food),
      non-food sensory play, fruit taste exposure, and control play. There were
      baseline differences in child fruit acceptance, so this was entered as a
      covariate into subsequent analyses. It was found that children in both the
      combined sensory play and non-food sensory play conditions enjoyed significantly
      more fruits at follow up than children in the control play condition, whilst
      children in the non-food sensory play group also enjoyed significantly more
      fruits than the fruit exposure group. These findings suggest that sensory play,
      with fruit and/or non-food substances, combined with exposure may be an effective
      strategy to increase tasting and fruit acceptance in children.

PMID- 29017907
TI  - The longitudinal link between mothers' and adolescents' snacking: The moderating
      role of television viewing.
AB  - A large proportion of adolescents eats too many energy-dense snacks, which is
      detrimental for their current and future health. To understand how to promote
      healthy dietary behaviors in adolescents, we need to identify factors that affect
      their snacking. While previous cross-sectional work has shown mother-child
      similarities in eating behavior, longitudinal studies are lacking. Hence, the
      first aim of this study was to examine whether maternal snacking predicted
      changes in adolescents' snacking over time. A second aim was to examine whether
      adolescents' television viewing magnified the strength of this longitudinal
      association. Television viewing may increase the motivation to eat the snacks
      consumed by mothers later on, for example through food advertisement exposure and
      mindless eating. To address both aims, 2051 adolescents (Mage baseline = 13.81;
      51.5% boys) were asked to report on their snacking and television viewing three
      times, with intervals of one year. Moreover, a subsample of mothers of
      adolescents (N = 1080) reported on their snacking at baseline as well. The
      results indicate that maternal snacking indeed predicts adolescents' snacking
      over time and that this effect is more pronounced among adolescents who watch a
      great amount of television. These findings attest to the importance of mothers in
      forming adolescents' snacking, not only concurrently but also prospectively.
      Additionally, this study highlights the relevance of assessing other home
      environmental factors that may influence maternal effects on their children's
      snacking.

PMID- 29017906
TI  - Clustering of multiple energy balance related behaviors is associated with body
      fat composition indicators in adolescents: Results from the HELENA and ELANA
      studies.
AB  - The objective of this study was to identify clustering patterns of four energy
      balance-related behaviors (EBRB): television (TV) watching, moderate and vigorous
      physical activity (MVPA), consumption of fruits and vegetables (F&V), and
      consumption of sugar-sweetened beverages (SSB), among European and Brazilian
      adolescents. EBRB associations with different body fat composition indicators
      were then evaluated. Participants included adolescents from eight European
      countries in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescents)
      study (n = 2,057, 53.8% female; age: 12.5-17.5 years) and from the metropolitan
      region of Rio de Janeiro/Brazil in the ELANA study (the Adolescent Nutritional
      Assessment Longitudinal Study) (n = 968, 53.2% female; age: 13.5-19 years). EBRB
      data allowed for sex- and study-specific clusters. Associations were estimated by
      ANOVA and odds ratios. Five clustering patterns were identified. Four similar
      clusters were identified for each sex and study. Among boys, different cluster
      identified was characterized by high F&V consumption in the HELENA study and high
      TV watching and high MVPA time in the ELANA study. Among girls, the different
      clusters identified was characterized by high F&V consumption in both studies
      and, additionally, high SSB consumption in the ELANA study. Regression analysis
      showed that clusters characterized by high SSB consumption in European boys; high
      TV watching, and high TV watching plus high MVPA in Brazilian boys; and high
      MVPA, and high SSB and F&V consumption in Brazilian girls, were positively
      associated with different body fat composition indicators. Common clusters were
      observed in adolescents from Europe and Brazil, however, no cluster was
      identified as being completely healthy or unhealthy. Each cluster seems to impact
      on body composition indicators, depending on the group. Public health actions
      should aim to promote adequate practices of EBRB.

PMID- 29017908
TI  - Visually suboptimal bananas: How ripeness affects consumer expectation and
      perception.
AB  - One reason for the significant amount of food that is wasted in developed
      countries is that consumers often expect visually suboptimal food as being less
      palatable. Using bananas as example, the objective of this study was to determine
      how appearance affects consumer overall liking, the rating of sensory attributes,
      purchase intention, and the intended use of bananas. The ripeness degree (RD) of
      the samples was adjusted to RD 5 (control) and RD 7 (more ripened, visually
      suboptimal). After preliminary experiments, a total of 233 participants were
      asked to judge their satisfaction with the intensity of sensory attributes that
      referred to flavor, taste, and texture using just-about-right scales. Subjects
      who received peeled samples were asked after tasting, whereas subjects who
      received unpeeled bananas judged expectation and, after peeling and tasting,
      perception. Expected overall liking and purchase intention were significantly
      lower for RD 7 bananas. Purchase intention was still significantly different
      between RD 5 and RD 7 after tasting, whereas no difference in overall liking was
      observed. Significant differences between RD 5 and RD 7 were observed when asking
      participants for their intended use of the bananas. Concerning the sensory
      attributes, penalty analysis revealed that only the firmness of the RD 7 bananas
      was still not just-about-right after tasting. The importance that consumers
      attribute to the shelf-life of food had a pronounced impact on purchase intention
      of bananas with different ripeness degree. In the case of suboptimal bananas, the
      results demonstrate a positive relationship between the sensory perception and
      overall liking and purchase intention. Convincing consumers that visually
      suboptimal food is still tasty is of high relevance for recommending different
      ways of communication.

PMID- 29017910
TI  - Developmental ethanol exposure alters the morphology of mouse prefrontal neurons
      in a layer-specific manner.
AB  - Chronic developmental exposure to ethanol can lead to a wide variety of
      teratogenic effects, which in humans are known as fetal alcohol spectrum
      disorders (FASD). Individuals affected by FASD may exhibit persistent impairments
      to cognitive functions such as learning, memory, and attention, which are highly
      dependent on medial prefrontal cortex (mPFC) circuitry. The objective of this
      study was to determine long-term effects of chronic developmental ethanol
      exposure on mPFC neuron morphology, in order to better-understand potential
      neuronal mechanisms underlying cognitive impairments associated with FASD.
      C57BL/6-strain mice were exposed to ethanol or an isocaloric/isovolumetric amount
      of sucrose (control) via oral gavage, administered both to the dam from
      gestational day 10-18 and directly to pups from postnatal day 4-14. Brains from
      male mice were collected at postnatal day 90 and neurons were stained using a
      modified Golgi-Cox method. Pyramidal neurons within layers II/III, V and VI of
      the mPFC were imaged, traced in three dimensions, and assessed using Sholl and
      branch structure analyses. Developmental ethanol exposure differentially impacted
      adult pyramidal neuron morphology depending on mPFC cortical layer. Neurons in
      layer II/III exhibited increased size and diameter of dendrite trees, whereas
      neurons in layer V were not affected. Layer VI neurons with long apical dendrites
      had trees with decreased diameter that extended farther from the soma, and layer
      VI neurons with short apical dendrite trees exhibited decreased tree size
      overall. These layer-specific alterations to mPFC neuron morphology may form a
      novel morphological mechanism underlying long-term mPFC dysfunction and resulting
      cognitive impairments in FASD.

PMID- 29017909
TI  - Objectively measuring effects of electro-acupuncture in parkinsonian rhesus
      monkeys.
AB  - Acupuncture has increasingly been used as an alternative therapy for treatment of
      Parkinson's disease (PD). However, the efficacy of acupunture for PD still
      remains unclear. The present study was designed to objectively and safely monitor
      anti-parkinsonian effects of electroacupuncture (EA) and brain activity in
      nonhuman primates modeling human PD. Six middle-aged rhesus monkeys were
      extensively studied by a computerized behavioral testing battery and by
      pharmacological MRI (phMRI) scans with specific dopaminergic drug stimulations.
      All animals were evaluated for behavior and phMRI responses under normal,
      parkinsonian, parkinsonian with EA treatment and parkinsonian after EA treatment
      conditions. Stable parkinsonian features were observed in all animals prior to
      entering the EA study and positive responses to levodopa (L-dopa) challenge were
      also seen in all animals. The results demonstrated that chronic EA treatments
      could significantly improve the movement speed and the fine motor performance
      time during the period of EA treatments, and the effectiveness of EA could be
      detected even 3 months after the EA treatment. The phMRI data revealed that
      chronic EA treatments could alter neuronal activity in the striatum, primary
      motor cortex (M1), cingulate gyrus and global pallidus externa (GPe) in the
      ipsilateral hemisphere to MPTP lesions. As seen in the changes of parkinsonian
      features, the residual effects of phMRI responses to apomorphine (APO) challenge
      could also be found in the aforementioned areas. The results strongly suggest
      that anti-parkinsonian effects of EA can be objectively assessed, and the method
      used in the present study could be translated into the human clinic with some
      minor modifications.

PMID- 29017911
TI  - Combination of a short cognitive training and tDCS to enhance visuospatial
      skills: A comparison between online and offline neuromodulation.
AB  - Visuospatial skills can be enhanced thanks to specific intervention programs, but
      the additional benefits of neuromodulation on these skills have not been fully
      investigated yet, although transcranial direct current stimulation (tDCS) has
      demonstrated to boost the effects of cognitive trainings. When combining
      cognitive intervention with neuromodulation, the time-window of tDCS application
      in relation to task execution has to be taken into account since it has been
      shown to affect stimulation outcomes. The aim of the present experiment was to
      investigate the influence of tDCS in enhancing the effects of a training for
      visuospatial skills. We hypothesized that tDCS applied during training execution
      (online) would improve the cognitive performance at a larger extent than tDCS
      applied before training execution (offline). Participants received anodal tDCS
      over the dorsolateral prefrontal cortex during (online) or before (offline) the
      completion of the training. A control sham condition was included. Visuospatial
      abilities were measured 24 h before (day 1, pre-test) and 24 h after (day 3, post
      test) the stimulation and training session (day 2). tDCS enhanced gains for
      mental folding performance when applied during the execution of the training
      (online). Participants' mental rotation and mental folding performance improved
      from pre-test to post-test regardless of the stimulation condition. However
      participants in the online tDCS condition showed the largest improvement in
      mental folding performance. Findings indicate that tDCS enhanced the effects of
      the training when applied during its execution, showing cumulative positive
      aftereffects on visuospatial performance 24 h after the stimulation session. The
      time-dependent effect points out the importance of the time-window of tDCS
      application in influencing behavior when combined with cognitive programs.

PMID- 29017912
TI  - CSF Abeta1-42, but not p-Tau181, differentiates aMCI from SCI.
AB  - AIM: Individuals with amnestic mild cognitive impairment (aMCI) are at a high
      risk to develop Alzheimer's disease (AD). We compared CSF levels of biomarkers of
      amyloidosis (Abeta1-42) and neurodegeneration (p-Tau181) in individuals with aMCI
      and with subjective cognitive impairment (SCI) in order to ascertain diagnostic
      accuracy and predict the odds ratio associated with aMCI. METHODS: We collected
      CSF of individuals clinically diagnosed with aMCI (33) and SCI (12) of a memory
      clinic of Southern Brazil. Levels of Abeta1-42 and p-Tau181 were measured by
      immunoenzymatic assay. Participants also underwent neuropsychological testing
      including the verbal memory test subscore of the Consortium to Establish a
      Registry for Alzheimer's Disease (VM-CERAD). RESULTS: CSF concentration of Abeta1
      42 was significantly lower (p: .007) and p-Tau181/Abeta1-42 ratio higher (p:
      .014) in aMCI individuals than in SCI. However, isolate p-Tau181 levels were not
      associated with aMCI (p: .166). There was a statistically significant association
      between Abeta1-42 and p-Tau181 (R2: 0.177; beta: -4.43; p: .017). ROC AUC of CSF
      Abeta1-42 was 0.768 and of the p-Tau181/Abeta1-42 ratio equals 0.742. Individuals
      with Abeta1-42 < 823 pg/mL levels were 6.0 times more likely to be diagnosed with
      aMCI (p: .019), with a 68.9% accuracy. Those with p-Tau181/Abeta1-42 ratio >
      0.071 were at 4.6 increased odds to have aMCI (p: .043), with a 64.5% accuracy.
      VM-CERAD was significantly lower in aMCI than among SCI (p: .041). CONCLUSION:
      CSF Abeta1-42, but not p-Tau181, level was significantly associated with aMCI.

PMID- 29017913
TI  - The use of natural compounds for the targeting and chemoprevention of ovarian
      cancer.
AB  - Among gynaecological cancers, ovarian cancer represents the leading cause of
      death in women. Current treatment for ovarian cancer entails surgery followed by
      combined chemotherapy with platinum and taxane, which are associated,
      particularly cisplatin, with severe side effects. While this treatment approach
      appears to be initially effective in a high number of patients, nearly 70% of
      them suffer a relapse within a few months after initial treatment. Therefore,
      more effective and better-tolerated treatment options are clearly needed. In
      recent years, several natural compounds (such as curcumin, epigallocatechin 3
      gallate (EGCG), resveratrol, sulforaphane and Withaferin-A), characterized by
      long-term safety and negligible and/or inexistent side effects, have been
      proposed as possible adjuvants of traditional chemotherapy. Indeed, several in
      vitro and in vivo studies have shown that phytocompounds can effectively inhibit
      tumor cell proliferation, stimulate autophagy, induce apoptosis, and specifically
      target ovarian cancer stem cells (CSCs), which are generally considered to be
      responsible for tumor recurrence in several types of cancer. Here we review
      current literature on the role of natural products in ovarian cancer
      chemoprevention, highlighting their effects particularly on the regulation of
      inflammation, autophagy, proliferation and apoptosis, chemotherapy resistance,
      and ovarian CSC growth.

PMID- 29017914
TI  - The roles of class I histone deacetylases (HDACs) in memory, learning, and
      executive cognitive functions: A review.
AB  - Coordinated changes in gene expression are critical for synaptic plasticity
      supporting learning, memory, and optimal cognitive task performance. These gene
      expression changes are not only mediated by signaling pathways that activate
      transcription factors, but also by chromatin modifications that influence the
      accessibility of the transcriptional machinery to specific genomic regions.
      During the past decade, evidence accumulated that alterations in chromatin-based
      epigenetic regulation of gene expression are linked to cognitive dysfunctions in
      the ageing or neurodegenerating brain as well as to cognitive dysfunctions
      resulting from chronic stress exposure. This review summarizes the results of
      studies that unraveled a role of histone modifying enzymes and histone
      modifications in normal and impaired learning and memory, and in the disruption
      of executive cognitive task performance. It emphasizes the different roles of
      specific class I histone deacetylases (HDACs) in cognitive processes governed by
      the hippocampus and prefrontal cortex and discusses the potential therapeutic
      implications of targeting them to hold the progression of disease-related
      cognitive dysfunctions.

PMID- 29017915
TI  - The neurobiology of body dysmorphic disorder: A systematic review and theoretical
      model.
AB  - There has been an increase in neuroimaging research in body dysmorphic disorder
      (BDD), yet little is known about the underlying neurobiological basis of the
      disorder. We aimed to provide a systematic overview of the literature on the
      neurobiology of BDD. Two reviewers undertook a search of three electronic
      research databases: PubMed, PsycINFO, and Google Scholar. The search consisted of
      synonyms commonly associated with BDD and methods to evaluate brain structure,
      function, and network organisation. Out of an initial yield of 175 articles, 19
      fulfilled inclusion criteria and were reviewed. We identified differences in
      brain activity, structure, and connectivity in BDD participants in
      frontostriatal, limbic, and visual system regions when compared to healthy
      control and other clinical groups. We put forth a neurobiological model of BDD
      pathophysiology that involves wide-spread disorganisation in neural networks
      involved in cognitive control and the interpretation of visual and emotional
      information. This review considers how this model might aid in the development of
      future research and understanding of BDD.

PMID- 29017916
TI  - Conflict detection and resolution rely on a combination of common and distinct
      cognitive control networks.
AB  - Cognitive control can be activated by stimulus-stimulus (S-S) and stimulus
      response (S-R) conflicts. However, whether cognitive control is domain-general or
      domain-specific remains unclear. To deepen the understanding of the functional
      organization of cognitive control networks, we conducted activation likelihood
      estimation (ALE) from 111 neuroimaging studies to examine brain activation in
      conflict-related tasks. We observed that fronto-parietal and cingulo-opercular
      networks were commonly engaged by S-S and S-R conflicts, showing a domain-general
      pattern. In addition, S-S conflicts specifically activated distinct brain regions
      to a greater degree. These regions were implicated in the processing of the
      semantic-relevant attribute, including the inferior frontal cortex (IFC),
      superior parietal cortex (SPC), superior occipital cortex (SOC), and right
      anterior cingulate cortex (ACC). By contrast, S-R conflicts specifically
      activated the left thalamus, middle frontal cortex (MFC), and right SPC, which
      were associated with detecting response conflict and orienting spatial attention.
      These findings suggest that conflict detection and resolution involve a
      combination of domain-general and domain-specific cognitive control mechanisms.

PMID- 29017917
TI  - fNIRS response during walking - Artefact or cortical activity? A systematic
      review.
AB  - This systematic review aims to (i) evaluate functional near infrared spectroscopy
      (fNIRS) walking study design in young adults, older adults and people with
      Parkinson's disease (PD); (ii) examine signal processing techniques to reduce
      artefacts and physiological noise in fNIRS data; and (iii) provide evidence-based
      recommendations for fNIRS walking study design and signal analysis techniques. An
      electronic search was undertaken. The search request detailed the measurement
      technique, cohort and walking task. Thirty-one of an initial yield of 73 studies
      satisfied the criteria. Protocols and methods for removing artefacts and noise
      varied. Differences in fNIRS signals between studies were found in rest vs.
      walking, speed of walking, usual vs. complex walking and easy vs. difficult
      tasks. In conclusion, there are considerable technical and methodological
      challenges in conducting fNIRS studies during walking which can introduce
      inconsistencies in study findings. We provide recommendations for the
      construction of robust methodologies and suggest signal processing techniques
      implementing a theoretical framework accounting for the physiology of
      haemodynamic responses.

PMID- 29017918
TI  - Comparative analysis of methicillin-sensitive and resistant Staphylococcus aureus
      exposed to emodin based on proteomic profiling.
AB  - Emodin has a strong antibacterial activity, including methicillin-resistant
      Staphylococcus aureus (MRSA). However, the mechanism by which emodin induces
      growth inhibition against MRSA remains unclear. In this study, the isobaric tags
      for relative and absolute quantitation (iTRAQ) proteomics approach was used to
      investigate the modes of action of emodin on a MRSA isolate and methicillin
      sensitive S. aureus ATCC29213(MSSA). Proteomic analysis showed that expression
      levels of 145 and 122 proteins were changed significantly in MRSA and MSSA,
      respectively, after emodin treatment. Comparative analysis of the functions of
      differentially expressed proteins between the two strains was performed via
      bioinformatics tools blast2go and STRING database. Proteins related to pyruvate
      pathway imbalance induction, protein synthesis inhibition, and DNA synthesis
      suppression were found in both methicillin-sensitive and resistant strains.
      Moreover, Interference proteins related to membrane damage mechanism were also
      observed in MRSA. Our findings indicate that emodin is a potential antibacterial
      agent targeting MRSA via multiple mechanisms.

PMID- 29017919
TI  - Whole-cell biopanning with a synthetic phage display library of nanobodies
      enabled the recovery of follicle-stimulating hormone receptor inhibitors.
AB  - Antibodies are essential reagents that are increasingly used in diagnostics and
      therapy. Their specificity and capacity to recognize their native antigen are
      critical characteristics for their in vivo application. Follicle-stimulating
      hormone receptor is a GPCR protein regulating ovarian follicular maturation and
      spermatogenesis. Recently, its potentiality as a cancer biomarker has been
      demonstrated but no antibody suitable for in vivo tumor targeting and treatment
      has been characterized so far. In this paper we describe the first successful
      attempt to recover recombinant antibodies against the FSHR and that: i) are
      directly panned from a pre-immune library using whole cells expressing the target
      receptor at their surface; ii) show inhibitory activity towards the FSH-induced
      cAMP accumulation; iii) do not share the same epitope with the natural binder
      FSH; iv) can be produced inexpensively as mono- or bivalent functional molecules
      in the bacterial cytoplasm. We expect that the proposed biopanning strategy will
      be profitable to identify useful functional antibodies for further members of the
      GPCR class.

PMID- 29017920
TI  - Mycophenolic mofetil, an alternative antiviral and immunomodulator for the highly
      pathogenic avian influenza H5N1 virus infection.
AB  - Infection with the highly pathogenic avian influenza H5N1 virus results in a high
      incidence of mortality in humans. Severe complications from infection are often
      associated with hypercytokinemia. However, current neuraminidase inhibitors
      (NAIs) have several limitations including the appearance of oseltamivir-resistant
      H5N1 virus and the inability to completely ameliorate hyper-immune responses. To
      overcome these limitations, we evaluated the anti-viral activity of mycophenolic
      mofetil (MMF) against A/Vietnam/1194/2004 (H5N1) virus infection using MDCK cells
      and mice. The IC50 of MMF (0.94 MUM) was comparable to that of zanamivir (0.87
      MUM) in H5N1 virus-infected MDCK cells based on ELISA. Time-course assays
      demonstrated that MMF completely inhibited H5N1 viral mRNA replication and
      protein expression for approximately 8 h after the initiation of treatment. In
      addition, MMF treatment protected 100% of mice, and lung viral titers were
      substantially reduced. The anti-viral mechanism of MMF against H5N1 virus
      infection was further confirmed to depend on the inhibition of cellular inosine
      monophosphate dehydrogenase (IMPDH) by exogenous guanosine, which inhibits viral
      mRNA and protein expression. Moreover, IL-1beta, IFN-beta, IL-6, and IP-10 mRNA
      expression levels were significantly downregulated in MDCK cells with MMF
      treatment. These results indicated that MMF could represent a novel inhibitor of
      viral replication and a potent immunomodulator for the treatment of H5N1 virus
      infection.

PMID- 29017921
TI  - Supervised machine learning techniques to predict binding affinity. A study for
      cyclin-dependent kinase 2.
AB  - Here we report the development of a machine-learning model to predict binding
      affinity based on the crystallographic structures of protein-ligand complexes. We
      used an ensemble of crystallographic structures (resolution better than 1.5 A
      resolution) for which half-maximal inhibitory concentration (IC50) data is
      available. Polynomial scoring functions were built using as explanatory variables
      the energy terms present in the MolDock and PLANTS scoring functions. Prediction
      performance was tested and the supervised machine learning models showed
      improvement in the prediction power, when compared with PLANTS and MolDock
      scoring functions. In addition, the machine-learning model was applied to predict
      binding affinity of CDK2, which showed a better performance when compared with
      AutoDock4, AutoDock Vina, MolDock, and PLANTS scores.

PMID- 29017922
TI  - Building kit for metal cation binding sites in proteins.
AB  - Starting with conformations of calcium-binding sites in parvalbumin and integrin
      (representative structures of EF-hand and calcium blade zones, respectively) we
      introduce four new different local Ca2+-recognition units in proteins: a one
      residue unit type I (ORI); a three-residue unit type I (TRI); a one-residue unit
      type II (ORII) and a three-residue unit type II (TRII). Based on the amount and
      nature of variable atoms, the type I and II units theoretically can have four and
      twelve variants, respectively. Analysis of known "Ca2+-bound functional niches"
      in proteins revealed presence of almost all possible variants of Ca2+-recognition
      units in actual structures. Parvalbumin, integrin alpha-IIb and sixteen other
      proteins with different Ca2+-bound functional niches contain various
      consecutively joined combinations of OR(I/II) and TR(I/II) units. Such a
      OR(I/II)+TR(I/II) joint unit forms a tripeptide, which uses three main-chain
      atoms for metal binding: nitrogenn (Donor), oxygenn (Acceptor) and nitrogenn+2
      (Donor). Thus, taken together, the described ORI, TRI, ORII and TRII units can
      serve as elementary blocks to construct more complex calcium recognizing
      substructures in a variety of calcium binding sites of unrelated proteins.

PMID- 29017923
TI  - Lysophosphatidylserine suppresses IL-2 production in CD4 T cells through
      LPS3/GPR174.
AB  - Lysophosphatidylserine (LysoPS) has been shown to have lipid mediator-like
      actions to induce mast cell degranulation and suppress T lymphocyte
      proliferation. Recently, three G protein-coupled receptors (GPCRs), LPS1/GPR34,
      LPS2/P2Y10, and LPS3/GPR174, were found to react specifically with LysoPS,
      raising the possibility that LysoPS exerts its roles through these receptors. In
      this study, we show that LPS3 is expressed in various T cell subtypes and is
      involved in suppression of Interleukin-2 (IL-2) production in CD4 T cells. We
      found that LysoPS suppressed the IL-2 production from activated T cells at the
      mRNA and protein levels. In addition, LysoPS did not have such an effect on the
      splenocytes and CD4 T cells isolated from LPS3-deficient mice. In LPS3-deficient
      splenocytes and CD4 T cells, anti-CD3/anti-CD28-triggered IL-2 production is
      somewhat increased. Interestingly, LysoPS with various fatty acids was up
      regulated upon T cell activation. The present study raised the possibility that
      LysoPS exerts its immunosuppressive roles by down-regulating IL-2 production
      through a LysoPS-LPS3 axis in T cells.

PMID- 29017924
TI  - LncRNA CPS1-IT1 suppresses EMT and metastasis of colorectal cancer by inhibiting
      hypoxia-induced autophagy through inactivation of HIF-1alpha.
AB  - OBJECTIVE: Hypoxia is a common phenomenon in solid tumor microenvironment.
      Thereby, the aim of this study was to investigate the molecular mechanisms of
      tumor metastasis and epithelial-mesenchymal transition (EMT) regulated by lncRNA
      CPS1 intronic transcript 1 (CPS1-IT1) under hypoxia in CRC. METHODS: Expression
      of lncRNA CPS1-IT1, hypoxia-inducible factor-1 alpha (HIF-1alpha) and autophagy
      related protein (LC3) were initially assessed in human CRC tissues and in a
      series of CRC cell lines. The relationship of CPS1-IT1, HIF-1alpha and autophagy
      were analyzed in CRC were performed through in vitro and in vivo functional
      assays. RESULTS: Expression of CPS1-IT1 were significantly reduced, while HIF
      1alpha and LC3-II were increased in CRC tissues and cell lines. Then, in vitro
      assays revealed that CPS1-IT1 suppresses EMT and autophagy by inhibiting the
      activation of HIF-1alpha in CRC. An in vivo animal model also demonstrated the
      tumor suppressor mechanism of CPS1- IT1. CONCLUSION: In this study, we found that
      hypoxia induce autophagy, and inhibition of autophagy could suppress tumor
      metastasis and EMT in CRC. Additionally, lncRNA CPS1-IT might suppresses
      metastasis and EMT by inhibiting hypoxia-induced autophagy through inactivation
      of HIF-1alpha in CRC.

PMID- 29017925
TI  - Evolution of catalytic microenvironment governs substrate and product diversity
      in trichodiene synthase and other terpene fold enzymes.
AB  - Trichodiene synthase, a terpene fold enzyme catalyzes the first reaction of
      trichodermin biosynthesis that is an economically important secondary metabolite.
      Sequence search analysis revealed that the proteins containing terpene fold are
      present in bacteria, fungi and plants. Terpene fold protein from Selaginella
      moellendorffii, a lycophyte, appeared at the interface of the microbes and plants
      in the evolutionary scale. Amino acid residues present around the catalytic
      pocket determines the size of the substrate as well as product molecules. It has
      been observed that the overall molecular evolution of the catalytic pockets
      dictates the choice of substrates/products of the proteins. It was further
      observed that N-terminus of multi-domain terpene fold proteins may assist in the
      interactions with the pyrophosphate part of the substrates. The phylogenetic
      analysis of these proteins further revealed that the enzymes are clustered into
      groups based on the domains present additional to the catalytic domains. We have
      also observed inter-domain 'puckering forceps' type motions in the multi-domains
      using normal mode analysis which were further correlated with their functions.
      The evolutionary clustering of these proteins was also influenced by the
      presence/absence of cofactor interacting motifs. These results may be used to
      modify/enhance the functions of these enzymes using protein engineering methods.

PMID- 29017926
TI  - Autonomic nervous system and pancreatic islet blood flow.
AB  - Vascularization and innervation of the islet of Langerhans are highly
      interconnected and are critical for intercellular and intertissular
      communication. They are both involved in the control of islet blood flow which
      has been shown to have an important role in the control of endocine secretion.
      Both parameters are disturbed during the course of metabolic pathologies and
      particularly diabetes. A better understanding of these mechanisms has and will
      greatly benefit from the rapidly-emerging technologies particularly in vivo
      imaging enabling to study both anatomy and functions of the islet.

PMID- 29017927
TI  - Eleclazine exhibits enhanced selectivity for long QT syndrome type 3-associated
      late Na+ current.
AB  - BACKGROUND: Eleclazine (GS-6615) is a sodium channel blocker designed to improve
      the selectivity for cardiac late Na+ current (INa) over peak INa. OBJECTIVES: The
      goals of this study were to investigate the inhibition of late INa by eleclazine
      using a sample of long QT syndrome type 3 (LQT3) and overlap LQT3/Brugada
      syndrome mutant channels; to compare the apparent binding rates for eleclazine
      with those for other class 1 antiarrhythmic agents; and to investigate the
      binding site. METHODS: Wild-type human cardiac voltage-gated sodium channel
      (hNaV1.5) and 21 previously reported variants were studied using patch clamp
      recordings from a heterologous expression system. RESULTS: Eleclazine inhibited
      anemone toxin II-enhanced late INa from wild-type hNaV1.5 with a drug
      concentration that causes 50% block of 0.62 +/- 0.12 MUM (84-fold selectivity
      over peak INa). The drug concentration that causes 50% block of eleclazine to
      inhibit the enhanced late INa from LQT3 mutant channels ranged from 0.33 to 1.7
      MUM. At predicted therapeutic concentrations, eleclazine and ranolazine inhibited
      peak INa to a similar degree as assessed with 4 overlap LQT3/Brugada syndrome
      mutations. Eleclazine was found to interact with hNaV1.5 significantly faster
      than ranolazine and 6 other class 1 antiarrhythmic agents. Engineered mutations
      (F1760A/Y1767A) located within the local anesthetic binding site decreased the
      inhibition of late INa and peak INa by eleclazine. CONCLUSION: At predicted
      therapeutic concentrations, eleclazine elicits potent inhibition of late INa
      across a cohort of NaV1.5 mutant channels. These properties are consistent with a
      class 1b antiarrhythmic agent that associates with unusually rapid
      binding/unbinding rates.

PMID- 29017928
TI  - Implantable cardioverter-defibrillator-computed respiratory disturbance index
      accurately identifies severe sleep apnea: The DASAP-HF study.
AB  - BACKGROUND: Sleep apnea (SA) is a relevant issue in the management of patients
      with heart failure for risk stratification and for implementing treatment
      strategies. OBJECTIVE: The purpose of this study was to evaluate in patients with
      implantable cardioverter-defibrillators (ICDs) the performance of the respiratory
      disturbance index (RDI) computed by the ApneaScan algorithm (Boston Scientific
      Inc., Natick, MA) as a discriminator of severe SA. METHODS: ICD-indicated
      patients with left ventricular ejection fraction <=35% were enrolled. One month
      after implantation, patients underwent a polysomnographic study. We evaluated the
      accuracy of the RDI for the prediction of severe SA (apnea-hypopnea index [AHI]
      >=30 episodes/h) and the agreement between RDI and AHI during the sleep study
      night. RESULTS: Two hundred sixty-five patients were enrolled to obtain the
      required sample of 173 patients with AHI and RDI data for analysis. The mean AHI
      was 21 +/- 15 episodes/h and severe SA was diagnosed in 38 patients (22%), while
      the mean RDI was 33 +/- 13 episodes/h. On the basis of the receiver operating
      characteristic curve analysis of RDI values, the area under the curve was 0.77
      (95% confidence interval [CI] 0.70-0.83; P < .001). At an RDI value of 31
      episodes/h, severe SA was detected with 87% (95% CI 72%-96%) sensitivity and 56%
      (95% CI 48%-66%) specificity. RDI closely correlated with AHI recorded during the
      same night (r = 0.74; 95% CI 0.57-0.84; P < .001), and the Bland-Altman agreement
      analysis revealed a bias of 11 episodes/h, with limits of agreement being -10 to
      32 episodes/h. CONCLUSION: The RDI accurately identified severe SA and
      demonstrated good agreement with AHI. Therefore, it may serve as an efficient
      tool for screening patients at risk of SA.

PMID- 29017929
TI  - Inappropriate sinus tachycardia-symptom and heart rate reduction with ivabradine:
      A pooled analysis of prospective studies.
AB  - BACKGROUND: Inappropriate sinus tachycardia (IST) is debilitating despite
      available treatment. Off-label use of ivabradine for IST prompted this systematic
      analysis of existing data quality and sample size estimates for adequately
      powered studies. OBJECTIVE: To determine clinical efficacy of ivabradine in IST
      from pooled prospective studies. METHODS: Analysis included ivabradine studies
      for IST participants without structural heart disease and with follow-up of >=2
      weeks. Heart rate and symptom reduction with ivabradine were estimated based on
      results of subjective change in symptoms assessed by various data instruments
      used in each study. Studies were assessed for quality using validated checklists.
      Sample sizes were calculated based on the magnitude of symptom reduction
      encountered after treatment with ivabradine. RESULTS: Nine studies met criteria,
      culminating in 145 patients pooled. Most patients were women (>=70%). Studies
      were small and not adequately powered, and all reported a decrease in maximum or
      mean resting heart rate or both, with complete or considerable amelioration of
      symptoms with ivabradine. Most studies had moderate quality with excellent
      consistency of study quality and narrow limits of agreement between the quality
      checklists. Sample size estimates for adequately powered studies with various
      placebo effects and comparisons with beta-blockade are reported. CONCLUSIONS:
      Ivabradine effectively reduces heart rate and symptoms in IST, but no study was
      adequately powered to account for the expected placebo effect on symptoms. A
      multicenter, randomized, placebo-controlled, active, comparative study with a
      beta-blocker is needed for confirmation. This is especially relevant given the
      ivabradine's potential teratogenic effect, as many IST patients are females of
      childbearing potential.

PMID- 29017930
TI  - Cardiac magnetic resonance imaging using wideband sequences in patients with
      nonconditional cardiac implanted electronic devices.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) has been performed safely in
      patients without MRI-conditional cardiac implantable electronic devices (CIEDs),
      but experience specifically with cardiac magnetic resonance imaging (CMR) is
      limited in this patient population. OBJECTIVE: Evaluate the safety of CMR in non
      MRI-conditional CIEDs and the interpretability of images using wideband
      sequences. METHODS: We performed 114 consecutive CMR studies in 111 patients
      (mean age 59 +/- 14 years, with 12 pacemakers, 73 implantable cardioverter
      defibrillators, 29 biventricular defibrillators) using a wideband pulse sequence
      for late gadolinium enhancement (LGE) imaging. A standardized protocol for device
      management and patient monitoring was followed. Patients were evaluated for major
      clinical adverse events and device parameter changes immediately after CMR and at
      clinical follow-up. RESULTS: In total, 111 CMR studies were completed
      successfully. There were no patient deaths, new arrhythmias, immediate generator
      or lead failures, electrical resets, or pacing capture failures in dependent
      patients. Right atrial, right ventricular, and left ventricular lead impedances
      were significantly lower post CMR, with median differences -7 Omega
      (interquartile range [IQR] -20 to 0 Omega; P < .0001), 0 Omega (IQR -19 to 0
      Omega; P = .0001), and -10 Omega (IQR -30 to 0 Omega; P = .023), respectively.
      These changes persisted through the follow-up period, with median differences 
      18.5 Omega (IQR -41 to -66 Omega; P = .007), -19 Omega (IQR -44 to -7 Omega; P =
      .006), and -30 Omega (IQR -130 to 0 Omega; P = .003), respectively. Ninety-seven
      studies (87%) had no artifact limiting interpretation. CONCLUSIONS: CMR can be
      performed safely in non-MRI-conditional CIEDs using a standardized protocol. Use
      of a wideband pulse sequence for LGE imaging yields a high rate of studies
      unaffected by artifact.

PMID- 29017932
TI  - Tanshinone I prevents atorvastatin-induced cerebral hemorrhage in zebrafish and
      stabilizes endothelial cell-cell adhesion by inhibiting VE-cadherin
      internalization and actin-myosin contractility.
AB  - Defects in vascular integrity in cerebrovasculature lead to serious pathologies
      including hemorrhagic stroke. The stability of cell adhesion junctions and actin
      myosin contractile machinery are two major determinants for the integrity of
      endothelial monolayer. Here we have evaluated the protective effects of
      tanshinone I (Tan I), a lipophilic compound presents in Salvia miltiorrhiza,
      against atorvastatin-induced cerebral hemorrhage in zebrafish in vivo, and
      further dissected the molecular mechanisms in HUVECs. We demonstrated that Tan I
      protected endothelial integrity by stabilizing cell-cell adhesion junctions via
      the inhibition of Src-mediated VE-cadherin internalization and subsequent
      junction-linked actin cytoskeleton depolymerization. In addition, Tan I inhibited
      ROCK-associated endothelial contractile machinery by dephosphorylating cofilin
      and MYPT1. These findings identified Tan I as an endothelial stabilizing agent
      and suggested Tan I as a potential treatment for vascular leakage in hemorrhagic
      stroke.

PMID- 29017933
TI  - Ten-year review of Clostridium difficile infection in acute care hospitals in the
      USA, 2005-2014.
AB  - Clostridium difficile infection (CDI) is a major health concern for acute care
      hospitals because of the increase in the number and severity of cases. Using the
      Nationwide Inpatient Sample database, a 10-year review was performed on the
      trends in incidence, mortality, and hospital charges for CDI patients in acute
      care hospitals during 2005-2014. The review found increased CDI incidence and
      hospital charges, but decreased mortality during the 10-year study period.

PMID- 29017931
TI  - Acute nicotine disrupts consolidation of contextual fear extinction and alters
      long-term memory-associated hippocampal kinase activity.
AB  - Previous research has shown that acute nicotine, an agonist of nAChRs, impaired
      fear extinction. However, the effects of acute nicotine on consolidation of
      contextual fear extinction memories and associated cell signaling cascades are
      unknown. Therefore, we examined the effects of acute nicotine injections before
      (pre-extinction) and after (post-extinction) contextual fear extinction on
      behavior and the phosphorylation of dorsal and ventral hippocampal ERK1/2 and
      JNK1 and protein levels on the 1st and 3rd day of extinction. Our results showed
      that acute nicotine administered prior to extinction sessions downregulated the
      phosphorylated forms of ERK1/2 in the ventral hippocampus, but not dorsal
      hippocampus, and JNK1 in both dorsal and ventral hippocampus on the 3rd
      extinction day. These effects were absent on the 1st day of extinction. We also
      showed that acute nicotine administered immediately and 30 min, but not 6 h,
      following extinction impaired contextual fear extinction suggesting that acute
      nicotine disrupts consolidation of contextual fear extinction memories. Finally,
      acute nicotine injections immediately after extinction sessions upregulated the
      phosphorylated forms of ERK1/2 in the ventral hippocampus, but did not affect
      JNK1. These results show that acute nicotine impairs contextual fear extinction
      potentially by altering molecular processes responsible for the consolidation of
      extinction memories.

PMID- 29017934
TI  - Validation of a national hand hygiene proxy measure in NHS Scotland.
AB  - The Scottish national hand hygiene proxy measure uses the volume of alcohol-based
      hand rub (ABHR) purchased by NHS Scotland boards as an indicator of the number of
      hand hygiene moments being performed per patient-bed-day. The proxy measure
      calculation is based on the assumption that 3 mL of ABHR is used per hand hygiene
      moment. This study aimed to validate the volume of ABHR being used per hand
      hygiene moment. It found that the median volume of ABHR being used in practice is
      approximately 1 mL per hand hygiene moment, and that using this validated volume
      in the calculation substantially increases the proxy measure of hand hygiene
      compliance.

PMID- 29017935
TI  - Physiological implications of DHEAS-induced non-classical steroid hormone
      signaling.
AB  - In the spermatogenic cell line GC-2, dehydroepiandrosterone sulfate (DHEAS),
      activates the Src/Ras/c-Raf/Erk1/2/CREB(ATF-1) signaling cascade. Since DHEAS is
      present in the gonads, and since spermatogenesis and maturation of spermatogonia
      to haploid spermatozoa requires activation of Erk1/2, the triggering of these
      signaling events by DHEAS might have physiological relevance. In the Sertoli cell
      line TM4, DHEAS-induces activation of Erk1/2, CREB, and ATF-1, stimulates
      expression of claudin-3 and claudin-5 and augments transepithelial resistance,
      indicating the formation of tight junctions between adjacent Sertoli cells. Thus,
      by influencing the formation and dynamics of tight junctions at the blood-testis
      barrier, which protects germ cells from cells of the immune system, DHEAS might
      play a crucial role in the regulation and maintenance of male fertility. In
      bEnd.3 brain-derived endothelial cells, DHEAS stimulates the expression of zonula
      occludens-1 and claudin-3 and promotes tight junction formation between
      neighboring cells, which at the blood-brain barrier protects the brain from
      harmful factors and cells. If DHEAS supports the integrity of the blood-brain
      barrier also in vivo, the current findings might lead to new strategies for the
      prevention or treatment of neurological disorders associated with barrier
      defects.

PMID- 29017936
TI  - Transporter for sulfated steroid hormones in the testis - expression pattern,
      biological significance and implications for fertility in men and rodents.
AB  - In various tissues, steroid hormones may be sulfated, glucuronidated or otherwise
      modified. For a long time, these hydrophilic molecules have been considered to be
      merely inactive metabolites for excretion via bile or urine. Nevertheless,
      different organs such as the placenta and breast tissue produce large amounts of
      sulfated steroids. After the discovery of the enzyme steroid sulfatase, which is
      able to re-activate sulfated steroids, these precursor molecules entered the
      focus of interest again as a local supply for steroid hormone synthesis with a
      prolonged half-life compared to their unconjugated counterparts. The first
      descriptions of this so-called sulfatase pathway in the placenta and breast
      tissue (with special regards to hormone-dependent breast cancer) were quickly
      followed by studies of steroid sulfate production and function in the testis.
      These hydrophilic molecules may not permeate the cell membrane by diffusion in
      the way that unbound steroids can, but need to be transported through the plasma
      membrane by transport systems. In the testis, a functional sulfatase pathway
      requires the expression of specific uptake carrier and efflux transporters in
      testicular cells, i.e. Sertoli, Leydig and germ cells. Main focus has to be
      placed on Sertoli cells, as these cells build up the blood-testis barrier. In
      this review, an overview of carrier expression pattern in the human as well as
      rodent testis is provided with special interest towards implications on
      fertility.

PMID- 29017938
TI  - WSSV-responsive gene expression under the influence of PmVRP15 suppression.
AB  - The viral responsive protein 15 from black tiger shrimp Penaeus monodon
      (PmVRP15), is highly up-regulated and produced in the hemocytes of shrimp with
      white spot syndrome virus (WSSV) infection. To investigate the differential
      expression of genes from P. monodon hemocytes that are involved in WSSV infection
      under the influence of PmVRP15 expression, suppression subtractive hybridization
      (SSH) of PmVRP15-silenced shrimp infected with WSSV was performed. The 189 cDNA
      clones of the forward library were generated by subtracting the cDNAs from WSSV
      infected and PmVRP15 knockdown shrimp with cDNAs from WSSV-infected and GFP
      knockdown shrimp. For the opposite subtraction, the 176 cDNA clones in the
      reverse library was an alternative set of genes in WSSV-infected shrimp hemocytes
      in the presence of PmVRP15 expression. The abundant genes in forward SSH library
      had a defense/homeostasis of 26%, energy/metabolism of 23% and in the reverse SSH
      library a hypothetical protein with unknown function was found (30%). The
      differential expressed immune-related genes from each library were selected for
      expression analysis using qRT-PCR. All selected genes from the forward library
      showed high up-regulation in the WSSV-challenged PmVRP15 knockdown group as
      expected. Interestingly, PmHHAP, a hemocyte homeostasis associated protein, and
      granulin-like protein, a conserved growth factor, are extremely up-regulated in
      the absence of PmVRP15 expression in WSSV-infected shrimp. Only transcript level
      of transglutaminase II, that functions in regulating hematopoietic tissue
      differentiation and inhibits mature hemocyte production in shrimp, was obviously
      down-regulated as observed from SSH results. Taken together, our results suggest
      that PmVRP15 might have a function relevant to hemocyte homeostasis during WSSV
      infection.

PMID- 29017937
TI  - Combined treatment of Biomphalaria glabrata infected by Schistosoma mansoni with
      oxamniquine and praziquantel: Reproductive histological and metabolic aspects.

PMID- 29017939
TI  - Identification of a novel toll gene (Shtoll3) from the freshwater crab
      Sinopotamon henanense and its expression pattern changes in response to cadmium
      followed by Aeromonas hydrophila infection.
AB  - Toll signaling is essential for expression of immune genes which are important
      for defense against bacterial, fungal and viral infections in invertebrates.
      Although several toll genes have been identified in the crustaceans, none of them
      has been investigated in freshwater crab Sinopotamon henanense. Moreover, the
      effect of cadmium (Cd) on toll gene expression has never been examined on the
      freshwater crabs which live in the sediments and are prone to heavy metal
      bioaccumulation. Our transcriptomic analysis of hepatopancreas tissue reveals
      that toll3 gene expression has been decreased when treated with Cd. In this
      study, we cloned one toll gene (hereby designated Shtoll3) from the crab. The
      full-length cDNA of Shtoll3 was 4488 bp, with an ORF of 3693 bp encoding a
      putative protein of 1230 amino acids, a 5'-untranslated region of 414 bp and a 3'
      untranslated region of 781 bp. Phylogenetic analysis showed that ShToll3 was
      clustered into the group of DmToll8. The tissue distribution results showed that
      Shtoll3 was expressed widely in different tissues, with the highest in gills, and
      the lowest in hemocytes. Shtoll3 expression was down-regulated only in midguts
      after Aeromonas hydrophila infection. With Cd presence, Shtoll3 expression in
      response to A. hydrophila were up-regulated in midguts and gills, which was
      further confirmed by western blotting analysis. Moreover, the mRNA level of two
      antimicrobial peptides (AMPs) crustin and c-lys, which possibly responded to Cd
      and A. hydrophila stimulation through Shtoll3, were analysised. Thus, we conclude
      that Cd changes the susceptibility of Shtoll3 to A. hydrophila infection in gills
      and midguts. This suggest that Shtoll3 may contribute to the innate immune
      defense of S. henanense to A. hydrophila and Cd can modify the immune function in
      epithelium.

PMID- 29017940
TI  - Single-walled carbon nanotubes as delivery vehicles enhance the immunoprotective
      effect of a DNA vaccine against spring viremia of carp virus in common carp.
AB  - Spring viremia of carp virus (SVCV) is highly contagious and pathogenic to
      cyprinid fish, causing enormous economic losses in aquaculture. Efficient and
      economic prophylactic measure against is the most pressing desired for the common
      carp farming industry. In this research, single-walled carbon nanotubes (SWCNTs)
      as a candidate DNA vaccine carrier was administrated via bath (1, 5, 10, 20, 40
      mg L-1) or injection (1, 4, 8, 12, 20 MUg) in common carp juvenile, and the
      different immune treatments to induce immunoprotective effect was analyzed. The
      results showed that higher levels of transcription and expression of G gene could
      be detected in muscle, spleen and kidney tissues via bath administration or
      intramuscular injection in SWCNTs-pEGFP-G treatment groups compared with naked
      pEGFP-G treatment groups. Meanwhile, complement activity, superoxide dismutase
      activity, alkaline phosphatase activity, immune-related genes (especially the TNF
      alpha) and antibody levels were significantly enhanced in fish immunized with DNA
      vaccine combined with SWCNTs. The relative percentage survival were significantly
      enhanced in fish bathed with SWCNTs-pEGFP-G vaccine and the relative percentage
      survival reached to 57.5% in SWCNTs-pEGFP-G group than that of naked pEGFP-G
      (40.0%) at the highest vaccine dose (40 mg L-1) after 22 days of post infection,
      and fish in bath immunization group at a concentration of 40 mg L-1 could reach
      the similar relative percentage survival in injection group at a dose of 12 MUg.
      This study suggest that ammonium-functionalized SWCNTs is the promising carrier
      for DNA vaccine and might be used to vaccinate large-scale juvenile fish by bath
      administration approach in aquaculture.

PMID- 29017941
TI  - Novel IFNgamma homologue identified in Nile tilapia (Oreochromis niloticus) links
      with immune response in gills under different stimuli.
AB  - Interferon gamma (IFN-gamma) has important roles in both innate and adaptive
      immune responses. This cytokine plays a very important role in defining Th1
      immune response in all vertebrates. In the present study, we identified and
      isolated for the first time the gene coding for Nile tilapia (Oreochromis
      niloticus) IFNgamma from spleen lymphocytes. The isolated tilapia IFNgamma has
      between 24 and 62% of amino acid identity as compared to reported sequences for
      other teleost fishes. It has close phylogenetic relationships with IFNgamma
      molecules belonging to the group of Perciforms and presents the typical
      structural characteristics of gamma interferon molecules. The tissue expression
      analysis showed that IFNgamma is expressed constitutively in head kidney, skin,
      intestine, muscle and brain. Its expression was not detected in gills by
      conventional RT-PCR. However, under conditions of stimulation with Poly I:C and
      LPS, IFNgamma expression was up-regulated in gills after 24 h post-stimulation.
      IFNgamma expression was also induced in gills 24 h after Edwardsiella tarda
      infection suggesting its important role in immunity against intracellular
      bacteria. The recombinant protein produced in Escherichia coli induced Mx gene
      transcription in head kidney primary culture cells. These results are the first
      steps to characterize the role of tilapia IFNgamma in the defense against
      pathogens in tilapia. Furthermore, the isolation of this molecule provides a new
      tool to characterize the cellular immune response to various stimuli in this
      organism.

PMID- 29017943
TI  - Efficacy and safety of a non-mineral oil adjuvanted injectable vaccine for the
      protection of Atlantic salmon (Salmo salar L.) against Flavobacterium
      psychrophilum.
AB  - Flavobacterium psychrophilum is the causative agent of Rainbow Trout Fry Syndrome
      which has had a major impact on global salmonid aquaculture. Recent outbreaks in
      Atlantic salmon in Scotland and Chile have added to the need for a vaccine to
      protect both salmon and trout. At present no licensed vaccines are available in
      Europe, leaving antibiotics as the only course of action to contain disease
      outbreaks. Outbreaks generally occur in fry at temperatures between 10 and 15 
      degrees C. Recently outbreaks in larger fish have given added impetus to the
      development of a vaccine which can provide long term protection from this highly
      heterogeneous pathogen. Most fish injectable vaccines are formulated with oil
      emulsion adjuvants to induce strong and long lasting immunity, but which are
      known to cause side effects. Alternative adjuvants are currently sought to
      minimise these adverse effects. The current study was performed to assess the
      efficacy of a polyvalent, whole cell vaccine containing formalin-inactivated F.
      psychrophilum to induce protective immunity in Atlantic salmon. The vaccine was
      formulated with an adjuvant containing squalene and aluminium hydroxide, and was
      compared to a vaccine formulated with a traditional oil adjuvant, Montanide ISA
      760VG, and a non-adjuvanted vaccine. Duplicate groups of salmon (23.5 +/- 6.8 g)
      were vaccinated with each of the vaccine formulations or phosphate buffered
      saline by intraperitoneal injection. Fish were challenged by intramuscular
      injection with F. psychrophilum six weeks post-vaccination to test the efficacy
      of the vaccines. Cumulative mortality reached 70% in the control salmon, while
      the groups of salmon that received vaccine had significantly lower mortality than
      the controls (p = 0.0001), with no significant difference in survival between
      vaccinated groups. The squalene/alum adjuvant was safe, more readily metabolised
      by the fish and induced less histopathological changes than the traditional oil
      adjuvant.

PMID- 29017942
TI  - As-CATH4 and 5, two vertebrate-derived natural host defense peptides, enhance the
      immuno-resistance efficiency against bacterial infections in Chinese mitten crab,
      Eriocheir sinensis.
AB  - Host defense peptides (HDPs), a class of conserved components of animal innate
      immune system, possess direct antimicrobial activities against invading pathogens
      and broadly participate in boosting and modulating host immune responses.
      Cathelicidins is an important family of HDPs that has been identified exclusively
      in vertebrates. Considering the relatively conserved innate immune system between
      invertebrates and vertebrates, it is speculated that HDPs from vertebrates may
      also possess modulating functions on invertebrate innate immune system. In the
      present study, two novel cathelicidins (As-CATH4 and 5), which had been
      identified from the Chinese alligator in our previous study, were employed to
      investigate their functions as novel peptide immunostimulants in Chinese mitten
      crab. As-CATH4 and 5 exhibited potent, broad-spectrum, and rapid antimicrobial
      activities against all the tested aquatic pathogenic bacteria. Unlike traditional
      antibiotics, they target on bacterial cell membrane, induce membrane
      permeabilization and cell disruption, and ultimately result in cell death. The
      antimicrobial effect is far more rapid than traditional antibiotics. Therefore
      they are unlikely to induce bacteria resistance. After the crabs were
      administered with As-CATH4 and 5, the activities of lysozyme, acid phosphatase
      and alkaline phosphatase were significantly enhanced, which indicated that the
      immune system of crabs could be activated by As-CATH4 and 5. In bacteria
      challenge test, As-CATH4 and 5 could significantly decrease the bacterial numbers
      in crabs, and increase the survival rates of crabs in both pre-stimulation and co
      stimulation groups. All of the results above indicated the great potential of As
      CATH4 and 5 as novel peptide immunostimulants in the crab aquaculture.

PMID- 29017944
TI  - Immunological responses and disease resistance of rainbow trout (Oncorhynchus
      mykiss) juveniles following dietary administration of stinging nettle (Urtica
      dioica).
AB  - The present study investigated the effects of dietary supplementation of stinging
      nettle (Urtica dioica) on growth performance, skin mucus, immune response and
      disease resistance of rainbow trout (Oncorhynchus mykiss) fed with diets
      supplemented with U. dioica at 0, 1, 2 and 3%. After 8 weeks of feeding, the
      addition of U. dioica at 3% level resulted in improved weight gain, specific
      growth rate and feed conversion ratio significantly when compared to the other
      groups (P < 0.05). Hematological responses including: hematocrit (Htc),
      hemoglobin (Hb), lymphocyte and neutrophil populations enhanced significantly in
      fish fed 3% of stinging nettle when measured after 4 weeks; while, total red
      blood cells, white blood, Htc, Hb, lymphocyte and neutrophil populations
      significantly increased after 8 weeks in the same group (P < 0.05). Total serum
      protein and glucose contents increased significantly in fish fed stinging nettle
      at 3% when compared to the other groups after 8 weeks; however, triglycerides
      decreased significantly in the same group on the 4th and 8th week (P < 0.05).
      Additionally, several immune parameters, namely, IgM, lysozyme, complement
      components C3 and C4, and respiratory burst of blood leukocytes significantly
      increased in the 3% fed group on the 4th week; while, after 8 weeks the immune
      responses enhanced in fish fed 2 and 3% diets (P < 0.05). At the end of the
      feeding trial, mucus samples obtained from the fish fed stinging nettle
      supplementation exhibited improved antagonistic activities against several
      bacterial pathogens (Streptococcus iniae, Yersinia ruckeri, Vibrio anguillarum
      and Lactococcus garviae), skin mucus enzymes activities (alkaline phosphatase,
      lysozyme, protease and esterase) and protein levels in 2 and 3% groups with the
      highest being in case of 3% group when compared to the other groups (P < 0.05).
      The cumulative mortality of rainbow trout subjected to Y. ruckeri infectious
      exhibited relatively low mortality levels in all supplemented groups with the
      lowest being in fish fed 3% stinging nettle. The present findings demonstrated
      that dietary administration of U. dioica enhanced growth and stimulated fish
      immunity; thus, enabling the fish to be more resistant against bacterial
      infections.

PMID- 29017945
TI  - Healing and mucosal immunity in the skin of experimentally wounded gilthead
      seabream (Sparus aurata L).
AB  - Skin lesions are very common in fisheries, increasing the risk of pathogens
      entering through the wounded skin of the fish. In the present assay, the
      progression of wound healing was studied over a 7 day period in gilthead seabream
      (Sparus aurata L.) after making experimental wounds in two different locations:
      above (group A) or below (group B) the lateral line. Macroscopic observation
      confirmed faster wound healing of the wounds of fish from group B. Furthermore,
      several immune-related components were studied in the skin mucus of wounded fish
      to ascertain whether wounding altered the mucus composition compared with the
      values obtained from non-wounded fish (group C, control). Significant variations
      were detected depending on both the site of the wound and the studied parameter.
      At the same time, the gene expression profile of several immune-relevant genes,
      including pro-inflammatory (il1b,il6, tnfa), anti-inflamamtory (tgfb, il10),
      immunoglobulins (ighm, ight), involved in oxidative stress (sod, cat) and in skin
      regeneration (krt1and grhl1) were studied in the three groups of fish (A, B and
      C). The results throw further light on the complex process of skin wound healing
      in fish, since substantial changes in the skin mucus and in the skin gene
      expression originated by the presence of wounds were observed. This work
      underline some important differences depending on the place of the fish body
      where the wound is located. Of particular note was the fact that such changes
      depended on the site of the wound.

PMID- 29017946
TI  - Cloning and expression of Malabar grouper (Epinephelus malabaricus) ADAR1 gene in
      response to immune stimulants and nervous necrosis virus.
AB  - ADARs are RNA editing catalysts that bind double-stranded RNA and convert
      adenosine to inosine, a process that can lead to destabilization of dsRNA
      structures and suppression of mRNA translation. In mammals, ADAR1 genes are
      involved in various cellular pathways, including interferon (IFN)-mediated
      response. However, the function of fish ADAR1 remains unclear. We report here the
      cloning of ADAR1 in Malabar grouper (Epinephelus malabaricus) (MgADAR1) and its
      response to various immune stimulants. The MgADAR1 cDNA is 5371-bp long,
      consisting of an open reading frame encoding a putative protein of 1381 amino
      acids, a 235-nt 5'-terminal untranslated region (UTR), and a 990-nt 3'-UTR. The
      deduced amino acid sequence exhibits signature features of a chitin synthesis
      regulation domain, two Z-DNA-binding domains (Z alpha), three dsRNA binding
      motifs (DSRM) and one tRNA-specific and dsRNA adenosine deaminase domain
      (ADEAMc). MgADAR1 mRNA expressed ubiquitously in tissues of healthy Malabar
      grouper, with elevated levels in the brain, gills and eyes. In response to poly
      (I: C), the MgADAR1 mRNA level was significantly up-regulated in the brain and
      spleen, but not head kidney. Upon nervous necrosis virus (NNV) infection the
      level of MgADAR1 increased in the brain, whereas Mx increased in the brain,
      spleen and head kidney. Induction of MgADAR1 by poly (I: C) and NNV was also
      observed in vitro. Additionally, the expression of MgADAR1 was upregulated by
      recombinant grouper IFN in grouper cells. These data indicate an intricate
      interplay between ADAR1 and NNV infection in grouper as MgADAR1 might be
      regulated in a tissue-specific manner.

PMID- 29017947
TI  - Integrated profiling of global metabolomic and transcriptomic responses to viral
      hemorrhagic septicemia virus infection in olive flounder.
AB  - Viral hemorrhagic septicemia virus (VHSV) is one of the most serious viral
      pathogen that infects farmed fish. In this study, we measured the replication of
      VHSV increased steadily at 9, 24, 72, and 120 h after infection and progression
      of necrosis was observed at 72 hpi. We performed transcriptomic and metabolomics
      profiling of kidney tissues collected at each infection time using Illumina
      HiSeq2000 and ultra-performance liquid chromatography/quadrupole time-of-flight
      mass spectroscopy to investigate the mechanisms of VHSV infection in the kidneys
      of olive flounder. A total of 13,862 mRNA molecules and 72 metabolites were
      selected to identify the mechanisms of infection and they were integrated using
      KEGG pathway database. Six KEGG metabolic pathways, including carbohydrate
      metabolism, amino acid metabolism, lipid metabolism, transport and catabolism,
      metabolism of cofactors and vitamins, and energy metabolism, were significantly
      suppressed, whereas the immune system was activated by VHSV infection. A decrease
      in levels of amino acids such as valine, leucine, and isoleucine, as well as in
      their derivative carnitines, was observed after VHSV infection. In addition, an
      increase in arachidonic acid level was noted. Integrated analysis of
      transcriptome and metabolome using KEGG pathway database revealed four types of
      responses in the kidneys of olive flounder to VHSV infection. Among these, the
      mechanisms related to the immune system and protein synthesis were activated,
      whereas ATP synthesis and the antioxidant system activity were suppressed. This
      is the first study describing the mechanisms of metabolic responses to VHSV
      infection in olive flounder. The results suggest that the suppression of ATP
      synthesis and antioxidant systems, such as glutathione and peroxisome signaling,
      could be the cause of necrosis, whereas the activation of the immune system could
      result in the inflammation of kidney tissue in VHSV-infected olive flounder.

PMID- 29017948
TI  - Transcriptome analysis of hepatopancraes of Procambarus clarkii challenged with
      polyriboinosinic polyribocytidylic acid (poly I:C).
AB  - Crustacean hepatopancreas regulates metabolic processes, biogenesis and innate
      immune processes, and the knowledge on its immune genes are crucial to understand
      antimicrobial mechanisms. In this study, we reported the transcriptomic profile
      of Procambarus clarkii hepatopancreas after poly I:C administration using high
      throughput sequencing. Following de novo assembly 56,716 unigene sequences with
      an average length of 810 bp was obtained. The unigene sequences were annotated to
      three ontologies including cellular components, biological processes and
      molecular functions, further 56,716 unigene sequences were mapped to 25 COG
      categories. A total of 2497 differentially expressed genes (DEGs) were identified
      following the comparative analysis between poly I:C treated and control group,
      and then KEGG enrichment analysis were performed to detect immune related
      pathways. Quantitative real time polymerase chain reaction showed that the
      selected DEGs significantly up-regulated following poly I:C administration in
      comparison to control group. The transcriptomic sequence information will improve
      the knowledge of this economically important crustacean, and will shed light on
      its antiviral immune mechanisms.

PMID- 29017949
TI  - Tumor necrosis factor receptor-associated factor 3 from Anodonta woodiana is an
      important factor in bivalve immune response to pathogen infection.
AB  - Tumor necrosis factor receptor-associated factor 3 (TRAF3) is a multifunctional
      adaptor protein in innate and acquired immune system that plays a key role in the
      regulation of the RIG-I-like receptor (RLR) and Toll-like receptor (TLR)
      signaling pathway in mammals. However, the immune function of TRAF3 homologs in
      freshwater mollusks is not well understood. In this study, we identified a
      bivalve TRAF3 gene (AwTRAF3) from Anodonta woodiana and investigated its
      potential roles during immune challenges. The present AwTRAF3 encoded a
      polypeptide of 562 amino acids with predicted molecular mass of 64.5 kDa and PI
      of 7.9. Similar to other reported TRAF3s, AwTRAF3 contained a RING finger domain,
      two TRAF domains with zinc finger domains, a coiled coli region and a conserved C
      terminal meprin and TRAF homology (MATH) domain. Quantitative real-time PCR (qRT
      PCR) analysis revealed that AwTRAF3 mRNA was broadly expressed in all of the
      examined tissues, with high expression in hepatopancreas, gill and heart. In
      addition, immune challenge experiments directly showed that transcript levels of
      AwTRAF3 in hepatopancreas were significantly regulated upon bacterial (Vibrio
      alginolyticus and Staphylococcus aureus) and viral (poly (I:C)) challenges,
      respectively. Moreover, GFP-tagged AwTRAF3 fusion protein was found to be located
      primarily in the cytoplasm in HEK293T cells. Altogether, these data provided the
      first experimental demonstration that freshwater mollusks possess a functional
      TRAF3 that was involved in the innate defense against bacterial and viral
      infection.

PMID- 29017950
TI  - The synergistic effects of valproic acid and fluvastatin on apoptosis induction
      in glioblastoma multiforme cell lines.
AB  - Glioblastoma multiforme (GBM) is the most common primary central nervous system
      malignant tumor. It responds poorly to standard therapies, such as surgical
      resection, radiation therapy and chemotherapy. Many chemotherapeutic drugs are
      focused on apoptosis induction and radiation sensitivity. Inhibition of histone
      acetylation via histone deacetylase inhibitor (HDACI) is one such strategy.
      Statins (or 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) are classical
      drugs used to lower cholesterol but also inhibitors of histone deacetylation
      activity. This study analyzes the combinatory effects of valproic acid (VPA) and
      fluvastatin on apoptosis induction in GBM8401 cells. The results show that they
      act synergistically in inducing gamma-H2AX and apoptosis accompanied by higher
      acetylated histones H3 and H4. Downregulation of p53 occurred by VPA alone and
      fluvastatin alone, but not at their combined application; upregulation of p21 at
      the protein level was induced by each of the drugs alone and no further increase
      occurred at combined application. The drug BEZ235 inhibited phosphorylation of
      Akt and attenuated the level of gamma-H2AX as well as cleaved PARP (cPARP)
      induced at combined application of VPA and fluvastatin. Induction of apoptosis
      within a 48h incubation period was massive when measured as the subG1 peak (97%)
      and was detected after a 24h incubation at low level when assayed with PE Annexin
      V. Synergistic apoptosis induction was demonstrated also after 24h incubation by
      the appearance of cPARP. Partial silencing of p21 reduced cPARP as well as the
      percentage of apoptotic cells in the subG1 peak. However, partial silencing of
      p53 had no effect on apoptosis. Such findings offer a better understanding of the
      mechanism of action of HDACIs in combination with statins that may guide the
      development of a new combinatory reposition for the treatment of GBM.

PMID- 29017951
TI  - Identification of CfiA coding genes in Bacteroides fragilis isolates recovered in
      Argentina. Inconsistencies in CfiA organization and nomenclature.
AB  - CfiA (CcrA) metallo-beta-lactamase is the main carbapenem resistance mechanism in
      B. fragilis. From cfiA positive isolates detected in a previous surveillance
      study, 3 displayed resistance to imipenem while the remaining were susceptible.
      The aim of this study was to identify the cfiA alleles and to analyze the
      presence of IS elements in their upstream regions. CfiA-1, CfiA-4, CfiA-13, CfiA
      19 and CfiA-22 were detected. IS elements belonging to IS21 family and IS942
      group were identified upstream to cfiA in the 3 imipenem resistant isolates. We
      present an exhaustive analysis of cfiA/CfiA registers in databases, illustrating
      the inconsistencies in both organization and nomenclature. According to this
      analysis CfiA family comprises nowadays 15 different CfiA variants coded by 24
      cfiA sequences. Curation of CfiA database is mandatory, if not new cfiA admission
      at GenBank will contribute to make this classification more complex.

PMID- 29017952
TI  - A biocompatible sodium alginate/povidone iodine film enhances wound healing.
AB  - In the last few years, there has been an increasing tendency to use natural
      polymers for the fabrication of dressings for wound and burn management. Among
      them, alginate, a polysaccharide extracted primarily from marine algae, exhibits
      attractive properties being non-toxic, hydrophilic and biodegradable. The aim of
      this study was to characterize the in vitro biocompatibility and the efficacy of
      a composite polymeric material based on sodium alginate (NaAlg) and povidone
      iodine (PVPI) complex in a mouse model of wound healing. The developed material
      combines the excellent wound healing properties of alginates with the
      bactericidal and fungicidal properties of PVPI, providing a controlled antiseptic
      release. We demonstrated that the NaAlg/PVPI films are able to reduce the
      inflammatory response both in human foreskin fibroblasts after lipopolysaccharide
      (LPS) stimulus and in rodents after wound induction. Furthermore, the NaAlg/PVPI
      film-treated animals showed a significantly higher wound closure compared to
      untreated animals at each time point considered. Interestingly, the complete
      wound closure was achieved within 12 days only in the film-treated group,
      indicating that the full-thickness wounds healed more rapidly in these animals.
      The results demonstrate that the NaAlg/PVPI films are biocompatible and possess
      healing properties that accelerate the wound closure.

PMID- 29017953
TI  - In vitro and in vivo study of pH-sensitive and colon-targeting P(LE-IA-MEG)
      hydrogel microspheres used for ulcerative colitis therapy.
AB  - Hydrocortisone sodium succinate (HSS) is an anti-inflammatory drug, but its
      application on ulcerative colitis (UC) treatment is limited by its associated
      side-effects. To solve this problem, a kind of pH-sensitive P(LE-IA-MEG) hydrogel
      microspheres (HMSs) were prepared as the drug carrier of hydrocortisone sodium
      succinate (HSS) for the treatment of UC. The P(LE-IA-MEG) HMSs were spherical in
      shape with good dispersion and the mean particle size was 34.87+/-0.90MUm. HSS
      was successfully loaded into the P(LE-IA-MEG) HMSs. The in vitro release study of
      HSS-loaded HMSs (HSS-HMSs) revealed that the HSS-HMSs possessed desirable pH
      sensitivity, the cumulative release rate was 4.07% and 94.64% in the solution
      with pH 1.2 and pH 7.4 solution during 12h, respectively. Furthermore, the study
      on pharmacokinetic, gastrointestinal drug residue and side-effects were conducted
      to evaluate the in vivo colon-targeting property of the HSS-HMSs. All the results
      showed that the HSS-HMSs could deliver HSS to the colon as well as reduce its
      premature absorption in the upper gastrointestinal tract. Finally, the HSS-HMSs
      showed better ameliorative effects and therapeutic effects on mice with
      experimental colitis as compared to HSS. In conclusion, the HSS-HMSs had great
      potential in the treatment of UC.

PMID- 29017954
TI  - Low level LED photodynamic therapy using curcumin loaded tetraether liposomes.
AB  - Oncological use of photodynamic therapy is an evolving field in cancer
      therapeutics. Photosensitisers are prone to accumulation inside healthy tissues
      causing undesirable effects. To avoid this, we have developed tetraether lipid
      liposomal formulations containing curcumin which is a naturally occurring anti
      cancer substance and deemed to be safe towards healthy cells. Upon excitation
      with light at a specific wavelength, curcumin produces reactive oxygen species
      (ROS) in presence of oxygen, thereby exhibiting a cytotoxic effect towards the
      surrounding tissues, giving a total control on the onset of therapy. In our
      study, we examined two different liposomal formulations wherein curcumin is
      encapsulated within the hydrophobic milieu with the intent to increase its
      bioavailability. Hydrodynamic diameter, surface charge, stability, morphology and
      haemocompatibility of the liposomes were studied. The results confirmed the
      formation of stable nanometre range liposomal vesicles (200-220 nm) containing
      curcumin which were haemocompatible with coagulation time less than 50 s and a
      haemolytic potential below 40%. Increased ROS generation post irradiation (>50%
      compared to un-irradiated samples) was confirmed using fluorescence spectroscopy.
      The efficiency and selectivity of the PDT was demonstrated by assessing their
      viability post irradiation and by qualitative analysis using confocal microscopy
      showing nuclear perforation induced by PDT. Photo-destructive effects of PDT on
      the microvasculature were studied in vivo using chick chorioallantoic membrane
      model (CAM). Considerable phototoxicity could be observed in the irradiated area
      of the CAM 30 min post irradiation. Phototoxic effects in vitro (in SK-OV-3 and
      PCS-100-020TM) and in vivo (in chorioallantoic membrane model) in combination
      with a novel custom manufactured LED irradiating device showed a formulation
      dependant selective photodynamic effect of the curcumin liposomes.

PMID- 29017956
TI  - Burden of Pneumonia-Associated Hospitalizations: United States, 2001-2014.
AB  - BACKGROUND: The epidemiology of pneumonia has likely evolved in recent years,
      reflecting an aging population, changes in population immunity, and socioeconomic
      disparities. METHODS: Using the National (Nationwide) Inpatient Sample, estimated
      numbers and rates of pneumonia-associated hospitalizations for 2001-2014 were
      calculated. A pneumonia-associated hospitalization was defined as one in which
      the discharge record listed a principal diagnosis of pneumonia or a secondary
      diagnosis of pneumonia if the principal diagnosis was respiratory failure or
      sepsis. RESULTS: There were an estimated 20,361,181 (SE, 95,601) pneumonia
      associated hospitalizations in the United States during 2001-2014 (average annual
      age-adjusted pneumonia-associated hospitalization rate of 464.8 per 100,000
      population [95% CI, 462.5-467.1]). The average annual age-adjusted pneumonia
      associated hospitalization rate decreased over the study period (P < .0001). In
      hospital death occurred in 7.4% (SE, 0.03) of pneumonia-associated
      hospitalizations. Non-Hispanic American Indian/Alaskan Natives and non-Hispanic
      blacks had the highest average annual age-adjusted rates of pneumonia-associated
      hospitalization of all race/ethnicities at 439.2 (95% CI, 415.9-462.5) and 438.6
      (95% CI, 432.5-444.7) per 100,000 population, respectively. During 2001-2014, the
      proportion of pneumonia-associated hospitalizations colisting an
      immunocompromising condition increased from 18.7% (SE, 0.2) in 2001 to 29.9% (SE,
      0.2) in 2014. Total charges for pneumonia-associated hospitalizations in 2014
      were over $84 billion. CONCLUSIONS: Pneumonia is a major cause of morbidity and
      mortality in the United States. Differences in rates and outcomes of pneumonia
      associated hospitalizations between sociodemographic groups warrant further
      investigation. The immunocompromised population has emerged as a group
      experiencing a disproportionate burden of pneumonia-associated hospitalizations.

PMID- 29017955
TI  - Triggering Receptor Expressed on Myeloid Cells-2 Expression Tracks With M2-Like
      Macrophage Activity and Disease Severity in COPD.
AB  - BACKGROUND: Cell and animal models show a key role for Triggering Receptor
      Expressed on Myeloid Cells (TREM)-2 in chronic airway disease after viral
      infection, but comparable evidence in humans still needs to be established.
      METHODS: Lung tissue samples were obtained from lung transplant recipients with
      Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV COPD (n =
      16), nontransplantable donor lung tissues (n = 7), and resected lung tissues from
      patients at risk or with GOLD stage I through IV (n = 55) and were assessed for
      TREM-2 and TREM-1 messenger RNA (mRNA), protein expression, and other markers of
      a type 2 immune response. RESULTS: TREM2 (but not TREM1) mRNA levels were
      increased in GOLD stage IV COPD lung tissues compared with non-COPD lung tissues.
      TREM2 mRNA was coexpressed with its signaling molecule DAP12 and the macrophage
      marker CD68 and M2-macrophage markers CD206 and CHIT1. TREM-2 protein was also
      increased in COPD lung tissues and was localized to CD14+ macrophages by flow
      cytometry and CD68+ and CCR2+ macrophages by tissue immunostaining. In lung
      samples from patients at risk and with GOLD stage I through IV COPD, TREM2 but
      not TREM1 mRNA levels were also increased, and the ratio of TREM2/TREM1 mRNA
      levels was associated with increases in CHIT1 mRNA and decreases in FEV1 and
      FEV1/FVC. CONCLUSIONS: TREM-2 expression is increased in lung macrophages in
      COPD, particularly in comparison with TREM-1. Therefore, TREM-2 levels and the
      ratio of TREM-2/TREM-1 signifies M2 activation in COPD lung tissues and may help
      to guide therapeutics directed against the type 2 immune response in patients
      with this disease.

PMID- 29017957
TI  - Lifetime Risks, Projected Numbers, and Adverse Outcomes in Asian Patients With
      Atrial Fibrillation: A Report From the Taiwan Nationwide AF Cohort Study.
AB  - BACKGROUND: Most data on the clinical epidemiology of atrial fibrillation (AF)
      come from Western populations, and data for Asians are limited. We investigated
      the lifetime risk and projected number of AF among Asians. The annual risks of
      adverse events among patients with AF, time trends, and the risks compared with
      patients without AF were analyzed. METHODS: Between 2000 and 2011, 289,559
      patients aged >= 20 years experienced new-onset AF in Taiwan. The incidence,
      prevalence, and lifetime risk of AF were calculated. The risk of adverse events
      among patients with AF were analyzed and compared with that of age- and sex
      matched patients without AF. RESULTS: The incidence of AF in year 2011 was 1.51
      per 1,000 person-years, with a lifetime risk of AF being appropriately 1 in 7 for
      subjects aged > 20 years. The prevalence of AF is estimated to be 4.01% in 2050.
      Compared with patients without AF, AF was associated with an increased risk of
      mortality (adjusted hazard ratio [aHR], 2.61), heart failure (aHR, 3.31),
      ischemic stroke (aHR, 3.34), dementia (aHR, 1.56), sudden cardiac death (aHR,
      1.83), and myocardial infarction (aHR, 1.62); all P < .01. The risks of ischemic
      stroke, heart failure, and mortality were especially higher compared with
      patients without AF in the initial period (approximately 6 months) after AF was
      first diagnosed. CONCLUSIONS: The burden of AF among Asian patients is
      increasing, with a lifetime risk of AF being 1 in 7. Optimized management of any
      associated comorbidities should be part of the holistic management approach for
      AF.

PMID- 29017958
TI  - Higher Priced Older Pharmaceuticals: How Should We Respond?
AB  - We and our patients have been aware of the high cost of medications in the United
      States for decades; however, we are now witnessing a relatively new phenomenon:
      exponential price increases for some older pharmaceuticals that have been
      available for years. To assist practitioners in how to respond to the issue of
      higher priced pharmaceuticals, an interprofessional session was developed and
      held at CHEST 2016 in Los Angeles. The session proceedings and a few updates are
      presented here to summarize what pulmonologists; a sarcoidosis expert; a retired
      executive of a medical society, an executive of a pharmaceutical company and of a
      pharmacy; and an ethicist advise that we do about the problem. Because the
      comments presented at the session and in this manuscript represent the opinions
      of each author, this commentary in essence is a compilation of nine editorials.
      It does not represent a comprehensive discussion of the field of pricing of
      drugs. In reflecting upon the answers to the questions posed, and regardless of
      their sector of health care, all participants stated that they focused on the
      patient. However, actually providing patient-focused care (ie, the care defined
      from the patient's perspective) is another matter. To significantly improve
      patient satisfaction and health-care outcomes, patient-focused care needs to
      embody the 3 Cs of (1) communication, (2) continuity of care, and (3) concordance
      of expectations (ie, finding the common ground). Therefore, we discuss how the 3
      Cs apply to responses to higher priced pharmaceuticals.

PMID- 29017959
TI  - 8-Isoprostane is an early biomarker for oxidative stress in chlorine-induced
      acute lung injury.
AB  - Inhalation of chlorine (Cl2) may cause oxidative acute lung injury (ALI)
      characterized by pulmonary edema, pneumonitis, and hyperreactive airways. The aim
      of the study was to identify possible biomarkers for Cl2-induced ALI. Female
      BALB/c mice were exposed to Cl2 for 15min using two protocols 1) concentration
      dependent response (25-200ppm) and 2) time-kinetics (2h-14days post-exposure).
      Exposure to 50-200ppm Cl2 caused a concentration-dependent inflammatory response
      with increased expression of IL-1beta, IL-6 and CXCL1/KC in bronchoalveolar
      lavage fluid 2-6h after exposure which was followed by increased lung
      permeability and a neutrophilic inflammation 12-24h post-exposure. The early
      inflammatory cytokine response was associated with a clear but transient increase
      of 8-isoprostane, a biomarker for oxidative stress, with its maximum at 2h after
      exposure. An increase of 8-isoprostane could also be detected in serum 2h after
      exposure to 200ppm Cl2, which was followed by increased levels of IL-6 and
      CXCL1/KC and signs of increased fibrinogen and PAI-1. Melphalan, a non-oxidizing
      mustard gas analog, did not increase the 8-isoprostane levels, indicating that 8
      isoprostane is induced in airways through direct oxidation by Cl2. We conclude
      that 8-isoprostane represents an early biomarker for oxidative stress in airways
      and in the blood circulation following Cl2-exposure.

PMID- 29017960
TI  - Upper respiratory tract nociceptor stimulation and stress response following
      acute and repeated Cyfluthrin inhalation in normal and pregnant rats:
      Physiological rat-specific adaptions can easily be misunderstood as adversities.
AB  - This paper reviews the results from past regulatory and mechanistic inhalation
      studies in rats with the type II pyrethroid Cyfluthrin. Apart from many chemical
      irritants, Cyfluthrin was shown to be a neuroexcitatory agent without any
      inherent tissue-destructive or irritant property. Thus, any Cyfluthrin-induced
      neuroexcitatory afferent sensory stimulus from peripheral nociceptors in the
      upper respiratory tract is likely to be perceived as a transient stimulus
      triggering annoyance and/or avoidance by both rats and humans. However, while
      thermolabile rats respond to such stresses reflexively, homeothermic humans
      appear to respond psychologically. With this focus in mind, past inhalation
      studies in rats and human volunteers were reevaluated and assessed to identify
      common denominators to such neuroexcitatory stimuli upon inhalation exposure.
      This analysis supports the conclusion that the adaptive physiological response
      occurring in rats secondary to such chemosensory stimuli requires inhalation
      exposures above the chemosensory threshold. Rats, a species known to undergo
      adaptively a hibernation-like physiological state upon environmental stresses,
      experienced reflexively-induced bradypnea, bradycardia, hypothermia, and changes
      in acid-base status during inhalation exposure. After cessation of the sensory
      stimulus, rapid recovery occurred. Physiological data of male and female rats
      from a 4-week repeated inhalation study (exposure 6-h/day, 5-times/week) were
      used to select concentration for a 10-day developmental inhalation toxicity study
      in pregnant rats. Maternal hypothermia and hypoventilation were identified as
      likely cause of fetal and placental growth retardations because of a maternal
      adaptation-driven reduced feto-placental transfer of oxygen. In summary, maternal
      reflex-hypothermia, reduced cardiac output and placental perfusion, and
      disruption of the gestation-related hyperventilation are believed to be the
      maternally mediated causes for developmental impairments. Thus, inhaled
      chemosensory substances may appear to be more toxic in rats than they will be in
      humans because the thermoregulatory response of rats to such stimuli can cause
      profound physiological adaptions that can easily be misunderstood as adversities
      in conventional inhalation studies in small rodents. The afferent threshold
      triggering such outcomes in rodents translate to perceptions of annoyance in
      humans. Consequently, hazard characterization and human risk assessment need to
      be focused on the chemosensory threshold rather than endpoints occurring
      downstream to rodent-specific homeostasis.

PMID- 29017961
TI  - Protection against Tetanus and Diphtheria in Europe: The impact of age, gender
      and country of origin based on data from the MARK-AGE Study.
AB  - Due to the successful implementation of vaccination strategies early-life
      morbidity and mortality due to infectious disease has been reduced dramatically.
      Vaccines against tetanus and diphtheria are among the most frequently used
      vaccines worldwide, but various studies in different European countries have
      shown that protection against tetanus and particularly against diphtheria is
      unsatisfactory in adults and older persons. In this study we analyzed tetanus-
      and diphtheria-specific antibody concentrations in 2100 adults of different age
      from 6 selected European countries (Austria, Belgium, Germany, Greece, Italy,
      Poland) in order to investigate differences in the level of protection against
      tetanus and diphtheria across Europe. Our data reveal that tetanus- and
      diphtheria-specific antibody concentrations vary greatly between countries, which
      is also reflected in the percentage of persons with antibody concentrations below
      the protective level (0.1IU/ml), which ranged from 2 to 31% percent for tetanus
      and 28-63% for diphtheria. In most countries, tetanus- and diphtheria-specific
      antibody concentrations decrease with age. This phenomenon is more pronounced in
      countries with generally low antibody levels, such as Italy, Poland and Greece.
      Interestingly, tetanus-specific antibody concentrations are generally higher in
      males than in females, which is probably due to vaccination during their military
      service or more frequent booster vaccinations after injuries, whereas no gender
      related differences were found for diphtheria-specific antibodies. In conclusion,
      our study demonstrates that the European population is not fully protected
      against tetanus and diphtheria. Measures to improve protection should include a
      life-long perspective on vaccination, more education to increase awareness of and
      compliance with vaccination guidelines, and a harmonization of recommendations
      and incentives across Europe.

PMID- 29017962
TI  - ACE I/D sequence variants but not MTHFR C677T, is strongly linked to malignant
      glioma risk and its variant DD genotype may act as a promising predictive
      biomarker for overall survival of glioma patients.
AB  - OBJECTIVE: ACE I/D and MTHFR C677T gene polymorphisms can be seen as candidate
      genes for glioma on the basis of their biological functions and their involvement
      in different cancers. The aim of this study was to analyze potential association
      and overall survival between MTHFR C677T and ACE I/D polymorphism in glioma
      patients in our population. MATERIALS AND METHODS: We tested genotype
      distribution of 112 glioma patients against 141 cancer-free controls from the
      same region. Kaplan-Meier survival analysis was performed to evaluate overall
      survival of patients for both genes. RESULTS: No significant differences were
      found among MTHFR C677T wild type C and variant genotypes CT/TT with glioma
      patients. In ACE, the distribution of variant ID and DD was found to be
      significantly higher in glioma cases as compared to controls (p<0.0001). ACE DD
      genotypes were highly presented in glioma cases 26.8% versus 10.6% in controls
      (p<0.0001) and conferred 5-fold risk for predisposition in glioma cases. Per copy
      D allele frequency was found higher in cases than in controls (0.54 versus 0.25:
      p<0.0001). Interestingly we found a significant overall survival (with log rank
      p<0.01) in patients who presented with ACE DD genotypes had the least estimated
      overall survival of 13.4months in comparison to 21. 7 and 17.6months for ACE II
      and I/D genotypes respectively. CONCLUSION: We conclude ACE I/D polymorphism
      plays a vital role in predisposition of higher risk for glioma. We also suggest
      that ACE DD genotypes may act as an important predictive biomarker for overall
      survival of glioma patients.

PMID- 29017963
TI  - The role of CXCL12 in tumor microenvironment.
AB  - The chemokine ligand C-X-C motif chemokine ligand 12 (CXCL12) is a kind of small
      molecules of cytokines that widely expressed in diversified tissues. Recent
      evidence suggests that CXCL12 plays an important role in the communication of
      tumor cells with their surrounding microenvironment. The interaction of CXCL12
      and its receptors subsequently excite the downstream signaling pathways to affect
      tumor angiogenesis, tumor cell proliferation and chemoresistance, and thus
      represents a potential target for cancer therapy. Outpouring molecules targeting
      CXCL12/CXCR4 axis in tumor microenvironment combined with traditional
      chemotherapy have drawn more and more attentions, which will be a promising
      method in anti-cancer therapies. Our review focuses on these roles of CXCL12 and
      summarizes strategies for treating cancer by disrupting this interaction with
      special emphasis on the CXCR4/CXCL12 axis.

PMID- 29017964
TI  - Isolation and characterization of a stress-responsive gene encoding a CHRD domain
      containing protein from a halotolerant green alga.
AB  - The genetic basis of stress resistance in extremophilic microalgae is not well
      studied. In this study, a gene of unknown function, the cluster58 or CL58 gene,
      was identified from the halotolerant green alga Chlamydomonas W80 and
      characterized. The CL58 gene encodes a protein containing a domain of unknown
      function, the CHRD domain, and a putative secretory signaling sequence at its N
      terminus. The levels of CL58 mRNA increased in response to high copper levels and
      low temperatures. When the CL58 gene was heterologously expressed as a fusion
      gene with the NanoLuc luciferase gene in Chlamydomonas reinhardtii, a majority of
      the NanoLuc activity was detected in the culture medium compared with that in the
      intracellular fraction. A mutagenic analysis revealed that the putative secretory
      signaling sequence was sufficient for the secretion of the CL58-NanoLuc fusion
      protein. In addition, we expressed the protein encoded by the CL58 gene in
      Escherichia coli; the recombinant, soluble protein was then purified. In summary,
      we identified a novel gene from C. W80 that appears to encode a stress
      responsive, CHRD domain-containing secreted protein.

PMID- 29017965
TI  - A novel mutation in HAUS7 results in severe oligozoospermia in two brothers.
AB  - Severe oligozoospermia (SO) is a common disease resulting in male infertility;
      however, its pathophysiology remains unclear. Here, we report two brothers with
      SO. Whole-exome sequencing (WES) identified a hemizygous variant in HAUS7
      (c.G386T:p.G129V), an X-linked gene. HAUS7 has been reported to play a role in
      the meiotic maturation and chromosome alignment of germ cells. The two patients
      inherited this variant from their mother, and this variant was considered to be a
      highly pathogenic mutation by in silico analysis. Moreover, in vitro
      fertilization (IVF)/intracytoplasmic sperm injection (ICSI) was carried out in
      both the proband's wife and the brother's wife, but they failed to become
      pregnant after the embryo transfers. Therefore, this novel mutation in HAUS7 gene
      may be associated with severe oligozoospermia.

PMID- 29017966
TI  - Comments on "Vitamin Pharmacogenomics: New Insight into Individual Differences in
      Diseases and Drug Responses".

PMID- 29017968
TI  - Author's Reply: Comments on "Vitamin Pharmacogenomics: New Insight into
      Individual Differences in Diseases and Drug Responses".

PMID- 29017969
TI  - Vigorous exercise mobilizes CD34+ hematopoietic stem cells to peripheral blood
      via the beta2-adrenergic receptor.
AB  - Acute dynamic exercise mobilizes CD34+ hematopoietic stem cells (HSCs) to the
      bloodstream, potentially serving as an economical adjuvant to boost the
      collection of HSCs from stem cell transplant donors. The mechanisms responsible
      for HSC mobilization with exercise are unknown but are likely due to hemodynamic
      perturbations, endogenous granulocyte-colony stimulating factor (G-CSF), and/or
      beta2-adrenergic receptor (beta2-AR) signaling. We characterized the temporal
      response of HSC mobilization and plasma G-CSF following exercise, and determined
      the impact of in vivo beta-AR blockade on the exercise-induced mobilization of
      HSCs. Healthy runners (n = 15) completed, in balanced order, two single bouts of
      steady state treadmill running exercise at moderate (lasting 90-min) or vigorous
      (lasting 30-min) intensity. A separate cohort of healthy cyclists (n = 12)
      completed three 30-min cycling ergometer trials at vigorous intensity after
      ingesting: (i) 10 mg bisoprolol (beta1-AR antagonist); (ii) 80 mg nadolol (beta1
      + beta2-AR antagonist); or (iii) placebo, in balanced order with a double-blind
      design. Blood samples collected before, during (runners only), immediately after,
      and at several points during exercise recovery were used to determine circulating
      G-CSF levels (runners only) and enumerate CD34+ HSCs by flow cytometry (runners
      and cyclists). Steady state vigorous but not moderate intensity exercise
      mobilized HSCs, increasing the total blood CD34+ count by ~4.15 +/- 1.62
      Deltacells/ul (+202 +/- 92%) compared to resting conditions. Plasma G-CSF
      increased in response to moderate but not vigorous exercise. Relative to placebo,
      nadolol and bisoprolol lowered exercising heart rate and blood pressure to
      comparable levels. The number of CD34+ HSCs increased with exercise after the
      placebo and bisoprolol trials, but not the nadolol trial, suggesting beta2-AR
      signaling mediated the mobilization of CD34+ cells [Placebo: 2.10 +/- 1.16 (207
      +/- 69.2%), Bisoprolol 1.66 +/- 0.79 (+163 +/- 29%), Nadolol: 0.68 +/- 0.54 (+143
      +/- 36%) Deltacells/uL]. We conclude that the mobilization of CD34+ HSCs with
      exercise is not dependent on circulating G-CSF and is likely due to the combined
      actions of beta2-AR signaling and hemodynamic shear stress.

PMID- 29017970
TI  - Absence of microglial CX3CR1 impairs the synaptic integration of adult-born
      hippocampal granule neurons.
AB  - Microglia are immune cells that play a crucial role in maintaining brain
      homeostasis. Among the mechanisms of communication between microglia and neurons,
      the CX3CL1/CX3CR1 axis exerts a central modulatory role. Animals lacking CX3CR1
      microglial receptor (CX3CR1-/- mice) exhibit marked alterations not only in
      microglia but also in neurons located in various regions of the brain. Here we
      show that microglial depletion of CX3CR1 leads to the deficient synaptic
      integration of adult-born granule neurons in the dentate gyrus (DG), both at the
      afferent and efferent level. Regarding the alterations in the former level, these
      cells show a reduced number of dendritic spines, which also exhibit morphological
      changes, namely enlargement and shortening. With respect to changes at the
      efferent level, these cells show a reduced area of axonal terminals. Both at the
      afferent and efferent level, synapses show ultrastructural enlargement, but they
      are depleted of synaptic vesicles, which suggests impaired functionality. We also
      show that selective increased microglial activation and extracellular matrix
      deposition in the zones in which the afferent synaptic contacts of these cells
      occur, namely in the molecular and the granule layer of the DG. In order to
      evaluate the impact of these structural alterations from a functional point of
      view, we performed a battery of behavioral tests related to hippocampal-dependent
      emotional behavior. We observed that female CX3CR1-/- mice exhibit a hyperactive,
      anxiolytic-like and depressive-like phenotype. These data shed light on novel
      aspects of the regulation of adult hippocampal neurogenesis by microglia that
      could be highly relevant for research into mood disorders.

PMID- 29017967
TI  - Non-coding RNAs and Their Roles in Stress Response in Plants.
AB  - Eukaryotic genomes encode thousands of non-coding RNAs (ncRNAs), which play
      crucial roles in transcriptional and post-transcriptional regulation of gene
      expression. Accumulating evidence indicates that ncRNAs, especially microRNAs
      (miRNAs) and long ncRNAs (lncRNAs), have emerged as key regulatory molecules in
      plant stress responses. In this review, we have summarized the current progress
      on the understanding of plant miRNA and lncRNA identification, characteristics,
      bioinformatics tools, and resources, and provided examples of mechanisms of miRNA
      and lncRNA-mediated plant stress tolerance.

PMID- 29017971
TI  - Induction of suppressor of cytokine signaling 3 via HSF-1-HSP70-TLR4 axis
      attenuates neuroinflammation and ameliorates postoperative pain.
AB  - Postoperative pain is a common form of acute pain that, if not managed
      effectively, can become chronic pain. Evidence has shown that glia, especially
      microglia, mediate neuroinflammation, which plays a vital role in pain
      sensitization. Moreover, toll-like receptor 4 (TLR4), the tumor necrosis factor
      receptor (TNF-R), the interleukin-1 receptor (IL-1R), and the interleukin-6
      receptor (IL-6R) have been considered key components in central pain
      sensitization and neuroinflammation. Therefore, we hypothesized that activation
      of the body's endogenous "immune brakes" will inhibit these receptors and achieve
      inflammation tolerance as well as relieve postoperative pain. After searching for
      potential candidates to serve as this immune brake, we identified and focused on
      the suppressor of cytokine signaling 3 (SOCS3) gene. To regulate SOCS3
      expression, we used paeoniflorin to induce heat shock protein 70 (HSP70)/TLR4
      signaling. We found that paeoniflorin significantly induced SOCS3 expression both
      in vitro and in vivo and promoted the efflux of HSP70 from the cytoplasm to the
      extracellular environment. Furthermore, paeoniflorin markedly attenuated incision
      induced mechanical allodynia, and this effect was abolished by small interfering
      RNAs targeting SOCS3. These findings demonstrated an effective and safe strategy
      to alleviate postoperative pain.

PMID- 29017972
TI  - Spirometry reference values for an andean high-altitude population.
AB  - : We compared the spirometric values of people living at High Altitude at the
      Andean Plateau with those predicted for lowland population. RATIONALE: Spirometry
      reference values are not yet available for the millions of people living at high
      altitude in the Andean High Plateau. OBJECTIVE: To obtain spirometric prediction
      equations from a healthy subset of adults living in Argentina at 3440m above sea
      level. METHODS: We randomly recruited 172 healthy men and 235 healthy women, ages
      20-70. Spirometry was done according to ATS/ERS standards. Reference equations
      were computed using regression analysis. RESULTS: The resulting prediction
      equations: For men: FVC=0.0407*height (cm)-0.0250*age(years)-0.81;SEE 0.518.
      FEV1=0.0327*height (cm)-0.0282*age(years)-0.25;SEE 0.414. For women:
      FVC(liters)=0.0464*height(cm)-0.0222*age(years)-2.62;SEE 0.396.
      FEV1(liters)=0.0343*height(cm)-0.0218*age(years)-1.40;SEE 0.316. CONCLUSIONS:
      These results establish spirometric-prediction equations for the population
      studied and further demonstrate: (1) a linear decline of FVC and FEV1 with age
      for both genders, (2) age and height satisfactorily predict both parameters, (3)
      supra-normal values for this population were found when compared to those
      predicted by lowland Caucasian equations.

PMID- 29017973
TI  - Modulating microfibrillar alignment and growth factor stimulation to regulate
      mesenchymal stem cell differentiation.
AB  - : The ideal tissue engineering (TE) strategy for ligament regeneration should
      recapitulate the bone - calcified cartilage - fibrocartilage - soft tissue
      interface. Aligned electrospun-fibers have been shown to guide the deposition of
      a highly organized extracellular matrix (ECM) necessary for ligament TE. However,
      recapitulating the different tissues observed in the bone-ligament interface
      using such constructs remains a challenge. This study aimed to explore how fiber
      alignment and growth factor stimulation interact to regulate the chondrogenic and
      ligamentous differentiation of mesenchymal stem cells (MSCs). To this end aligned
      and randomly-aligned electrospun microfibrillar scaffolds were seeded with bone
      marrow derived MSCs and stimulated with transforming growth factor beta3
      (TGFbeta3) or connective tissue growth factor (CTGF), either individually or
      sequentially. Without growth factor stimulation, MSCs on aligned-microfibers
      showed higher levels of tenomodulin (TNMD) and aggrecan gene expression compared
      to MSCs on randomly-oriented fibers. MSCs on aligned-microfibers stimulated with
      TGFbeta3 formed cellular aggregates and underwent robust chondrogenesis,
      evidenced by increased type II collagen expression and sulphated
      glycosaminoglycans (sGAG) synthesis compared to MSCs on randomly-oriented
      scaffolds. Bone morphogenetic protein 2 (BMP2) and type I collagen gene
      expression were higher on randomly-oriented scaffolds stimulated with TGFbeta3,
      suggesting this substrate was more supportive of an endochondral phenotype. In
      the presence of CTGF, MSCs underwent ligamentous differentiation, with increased
      TNMD expression on aligned compared to randomly aligned scaffolds. Upon
      sequential growth factor stimulation, MSCs expressed types I and II collagen and
      deposited higher overall levels of collagen compared to scaffolds stimulated with
      either growth factor in isolation. These findings demonstrate that modulating the
      alignment of microfibrillar scaffolds can be used to promote either an
      endochondral, chondrogenic, fibrochondrogenic or ligamentous MSC phenotype upon
      presentation of appropriate biochemical cues. STATEMENT OF SIGNIFICANCE:
      Polymeric electrospun fibers can be tuned to match the fibrillar size and
      anisotropy of collagen fibers in ligaments, and can be mechanically competent.
      Therefore, their use is attractive when attempting to tissue engineer the bone
      ligament interface. A central challenge in this field is recapitulating the
      cellular phenotypes observed across the bone-ligament interface. Here we
      demonstrated that it is possible to direct MSCs seeded onto aligned electrospun
      fibres towards either a ligamentogenic, chondrogenic or fibrochondrogenic
      phenotype upon presentation of appropriate biochemical cues. This opens the
      possibility of using aligned microfibrillar scaffolds that are spatially
      functionalized with specific growth factors to direct MSC differentiation for
      engineering the bone-ligament interface.

PMID- 29017974
TI  - Vectofusin-1, a potent peptidic enhancer of viral gene transfer forms pH
      dependent alpha-helical nanofibrils, concentrating viral particles.
AB  - Gene transfer using lentiviral vectors has therapeutic applications spanning from
      monogenic and infectious diseases to cancer. Such gene therapy has to be improved
      by enhancing the levels of viral infection of target cells and/or reducing the
      amount of lentivirus for greater safety and reduced costs. Vectofusin-1, a
      recently developed cationic amphipathic peptide with a pronounced capacity to
      enhance such viral transduction, strongly promotes the entry of several
      retroviral pseudotypes into target cells when added to the culture medium. To
      clarify the molecular basis of its action the peptide was investigated on a
      molecular and a supramolecular level by a variety of biophysical approaches. We
      show that in culture medium vectofusin-1 rapidly forms complexes in the 10 nm
      range that further assemble into annular and extended nanofibrils. These
      associate with viral particles allowing them to be easily pelleted for optimal
      virus-cell interaction. Thioflavin T fluorescence, circular dichroism and
      infrared spectroscopies indicate that these fibrils have a unique alpha-helical
      structure whereas most other viral transduction enhancers form beta-amyloid
      fibrils. A vectofusin-1 derivative (LAH2-A4) is inefficient in biological assays
      and does not form nanofibrils, suggesting that supramolecular assembly is
      essential for transduction enhancement. Our observations define vectofusin-1 as a
      member of a new class of alpha-helical enhancers of lentiviral infection. Its
      fibril formation is reversible which bears considerable advantages in handling
      the peptide in conditions well-adapted to Good Manufacturing Practices and
      scalable gene therapy protocols.

PMID- 29017975
TI  - Suturing Treatment for Blood Blister-Like Aneurysm in Supraclinoid Segment of
      Internal Carotid Artery.
AB  - BACKGROUND: Blood blister-like aneurysms (BBAs) are rare but dangerous and
      challenging to treat. Recurrence and rebleeding are often reported, and many
      neurosurgeons and interventional radiologists are discouraged by such poor
      outcomes. Currently, there is no standard method to treat this type of aneurysm.
      CASE DESCRIPTION: We describe 5 cases of ruptured BBAs in the supraclinoid
      segment of the internal carotid artery, which were treated successfully using a
      suturing technique. No patient experienced recurrence or rebleeding, and all
      patients had a good prognosis. CONCLUSIONS: We conclude that this suturing
      technique is an optional safe and reliable method to treat BBAs.

PMID- 29017976
TI  - Outcomes After Transcranial and Endoscopic Endonasal Approach for Tuberculum
      Meningiomas-A Retrospective Comparison.
AB  - BACKGROUND: Degree of resection and visual outcome are the main concerns in the
      surgical resection of tuberculum sellae meningioma (TSM). In addition to the
      transcranial approach (TCA), the endoscopic endonasal approach (EEA) has been
      used increasingly. However, the controversy regarding the optimal surgical
      approach is not clearly resolved. METHODS: We compared the surgical outcomes of
      each approach for TSMs from 44 patients receiving EEA and 40 patients receiving
      TCA in 2 institutions between 2004 and 2015. We analyzed the surgical outcomes
      and affecting factors for the relapse of tumor and visual outcome. RESULTS: Gross
      total resection rates and relapse-free survival were not different between the 2
      groups; however, the locations of residual or recurred tumor definitely differed.
      All recurrences in the TCA group were in the sella turcica, whereas residual
      tumors in EEA group were mainly located at lateral or superior to the clinoid
      process. The complete or partial improvement rate of visual function in the EEA
      group was 97.7%, but 9 patients (23.7%) in the TCA group experienced visual
      deterioration after surgery. EEA and younger age (<55 years) were associated with
      favorable visual outcome. Cerebrospinal fluid leakage occurred in only one case
      in the EEA group. CONCLUSIONS: Surgical approaches do not affect the gross total
      resection rates, but the locations of residual tumor or recurrence differ
      according to surgical approaches. EEA is superior to TCA in visual outcome. At
      least in pure TSMs, the trend seems to be shifting in favor of EEA, considering
      the huge difference in visual outcome.

PMID- 29017977
TI  - Syrinx to Subarachnoid Shunting for Syringomyelia.
AB  - OBJECTIVE: Surgery for syringomyelia generally aims to treat the underlying
      cause, if it is known. Optimal management is unclear for idiopathic
      syringomyelia, or when treatment of the putative cause has failed or is high
      risk. Syrinx to subarachnoid shunting is an option for these cases; a series is
      reported to assess the outcomes of this approach. METHODS: We retrospectively
      analyzed the clinical and radiologic features of a consecutive series of patients
      with syringomyelia treated with syrinx to subarachnoid shunting. RESULTS: Forty
      one patients (19 male, 4-79 years old) were treated from 2000 to 2016, including
      15 patients with idiopathic syringomyelia, 13 with spinal trauma, 5 with Chiari
      malformation, 4 with arachnoiditis, 3 with tethered cord, and 1 with arachnoid
      bands. The patients were treated with a syrinx to subarachnoid shunt, and a
      subset also underwent expansile duraplasty. At follow-up (3-108 months, mean 36
      months) syrinx size was reduced in 37 patients, and there was improvement or
      stabilization of symptoms in all but 1 patient. Three patients had temporary
      lower limb sensory symptoms after surgery. Other complications were 2 transient
      cerebrospinal fluid leaks, a pseudomeningocoele, and 1 postoperative myocardial
      infarction. Two cases of shunt dislodgement required reoperation, and a third
      case required early reoperation for an enlarging syrinx. There were no cases of
      shunt blockage or infection. CONCLUSIONS: Syrinx to subarachnoid shunting is a
      safe and effective treatment for idiopathic syringomyelia and for patients who
      are not suitable for, or have not responded to, other treatment.

PMID- 29017978
TI  - Cranial Base Meningiomas.

PMID- 29017979
TI  - Transdural Spinal Cord Herniation: Tips and Tricks.
AB  - Recognition of transdural spinal cord herniation has increased over the past
      decade. This condition remains little known, particularly outside the specialized
      fields of spinal surgery and neuroradiology, leading to a significant delay in
      clinical diagnosis and treatment. It should be considered among the differential
      diagnoses in patients with gradual-onset lower-limb weakness of presumed spinal
      origin. Reaching a diagnosis using magnetic resonance imaging is essential to
      refer patients for surgery before their myelopathy worsens. We describe our
      surgical experience to untether the spinal cord by wrapping a dura graft around
      the spinal cord. Three case reports and a review of the literature are discussed.

PMID- 29017980
TI  - Predisposing Factors of Fracture Nonunion After Posterior C1 Lateral Mass Screws
      Combined with C2 Pedicle/Laminar Screw Fixation for Type II Odontoid Fracture.
AB  - INTRODUCTION: The aim of this study was to explore the predisposing factors for
      fracture nonunion after a lateral screw was combined with C2 pedicle/laminar
      screw for a type II odontoid fracture and hopefully provide references in
      decision making and surgical planning for spinal surgeons. METHODS: This is a
      retrospective study. By retrieving the medical records from January 2010 to July
      2015 in our hospital, 117 type II odontoid fracture patients were reviewed.
      According to the occurrence of fracture union at the final follow-up, patients
      were divided into 2 groups: union and nonunion. To investigate the predisposing
      factors for fracture nonunion, 3 categorized factors were analyzed statistically:
      patient characteristics-age, sex, body mass index, preoperative Japanese
      Orthopaedic Association (JOA) scores, duration, comorbidity, and complicated
      injuries; surgical variables-surgery time, blood loss, C2 fixation manner,
      vertebral artery injury, bone source for fusion between the posterior arch of C1
      and the laminae and spinous process of C2; radiographic parameters-preoperative
      and immediate postoperative data of C0-2 curvature, C2-7 curvature, C2-7 sagittal
      vertical axis, C7 slope, fracture classification, congenital hypoplastic
      vertebral artery, and the separation and displacement of the odontoid fracture.
      Other variables including JOA and visual analog scale scores for neck pain, neck
      stiffness, and patient satisfaction at final follow-up were recorded and compared
      between the 2 groups. RESULTS: Postoperative fracture nonunion was detected in 76
      of 117 patients (65%) at final follow-up. There was no statistically significant
      difference between the 2 groups in patient characteristics of sex, body mass
      index, JOA score, comorbidity, and complicated injuries. The mean age at
      operation was younger in the union group than in the nonunion group, and the mean
      duration was shorter in the union group than in the nonunion group. There was no
      difference in surgical variables of surgery time, blood loss, C2 fixation manner,
      vertebral artery injury, bone source for fusion between the posterior arch of C1
      and the laminae and spinous process of C2. There was no difference in
      radiographic parameters of fracture classification, congenital hypoplastic
      vertebral artery, preoperative and immediate postoperative C0-2 curvature, C2-7
      curvature, C2-7 SVA, and C7 slope. No difference was found in preoperative and
      immediate postoperative displacement of the odontoid fracture or immediate
      postoperative separation of the odontoid fracture, while the preoperative
      separation of the odontoid fracture was shorter in the union group than in the
      nonunion group. The logistic regression analysis revealed that advanced age (>45
      years), long duration (>2 months), and preoperative separation of the odontoid
      fracture (>4 mm) were independently associated with the postoperative fracture
      nonunion. There were no differences between the 2 groups in JOA, neck pain, neck
      stiffness, and patient satisfaction at final follow-up. CONCLUSIONS: Advanced
      age, long duration, and preoperative separation of odontoid fracture >4 mm are
      predisposing factors for fracture nonunion after posterior C1 lateral screw
      combined with C2 pedicle/laminar screw fixation for type II odontoid fracture.
      Our findings did not demonstrate any evidence of lower functional outcome and
      patients satisfaction for those patients who had odontoid nonunion.

PMID- 29017981
TI  - Prolonged Intracisternal Papaverine Toxicity: Index Case Description and Proposed
      Mechanism of Action.
AB  - BACKGROUND: Intracisternal papaverine (iPPV) is a vasodilator used for
      prophylaxis of intraoperative vasospasm during aneurysmal clipping. Postoperative
      side effects of iPPV include transient cranial nerve palsies, most commonly
      mydriasis owing to oculomotor nerve involvement, with rapid resolution. METHODS:
      We critically reviewed current literature on the adverse effects of iPPV in
      aneurysmal surgery with a focus on oculomotor nerve involvement. We also present
      the index case of prolonged bilateral mydriasis secondary to iPPV irrigation
      toxicity and its putative underlying mechanism. RESULTS: Papaverine toxicity
      occurs in the setting of its antimuscarinic action and blood-cerebrospinal fluid
      and blood-brain barrier compromise owing to acute subarachnoid hemorrhage and
      direct effect of papaverine. Our patient also experienced severe vasospasm and a
      minor stroke, both contributing to further blood-brain barrier disruption, and
      relatively acidic pH of the subarachnoid hemorrhage milieu. CONCLUSIONS: We
      propose that these factors perpetuate phase dynamics of papaverine crystals and
      facilitate a sustained slow release of papaverine within the cisternal system.
      Were it indicated, 0.3% iPPV would reasonably diminish the risk for
      neurotoxicity.

PMID- 29017982
TI  - Clinical Presentation, Diagnosis, and Surgical Treatment of Spontaneous Cervical
      Intradural Disc Herniations: A Review of the Literature.
AB  - OBJECTIVE: Spontaneous cervical intradural disc herniation (IDH) is a rare
      occurrence with limited and disparate information available regarding its
      presentation, diagnosis, and treatment. However, its accurate detection is vital
      for planning surgical treatment. In this review of the literature, we collected
      data from all cervical IDHs described to date. Particular attention was paid to
      diagnostic findings, surgical approach, and causation for cervical IDH,
      especially at the cervicothoracic junction. METHODS: A review for cases of
      cervical IDH was performed via the following search criteria: ("neck"[MeSH Terms]
      OR "neck"[All Fields] OR "cervical"[All Fields]) AND intradural[All Fields] AND
      disc[All Fields]. Thirty-seven cases of cervical disc herniation were identified.
      Demographic variables identified included age, sex, cervical level of herniation,
      history of associated cervical trauma, presence of Brown-Sequard syndrome, Horner
      syndrome, and other neurologic findings, radiographic findings, direction of
      surgical approach, and postoperative outcomes. RESULTS: A total of 37 cases of
      cervical IDH were identified. Most of the cases occurred at the lower levels of
      the cervical spine, with 35.1% at the C5-C6 level, followed by 24.3% at C6-C7,
      and lower still at other levels. Of the patients reviewed, 44.4% had a previous
      history of trauma before manifestation of symptom, with the majority being
      spontaneous IDH with no previous history of trauma or spine surgery. Brown
      Sequard syndrome was present in 43.2% of the patients, whereas 10.8% of patients
      experienced Horner syndrome. The most common presentations of IDH included
      quadriplegia, finger/gait ataxia, radiculopathy, and nuchal pain. The degree of
      neurologic recovery was not associated with patient age. Most of the cervical
      IDHs in the literature were treated surgically via an anterior approach, but a
      larger portion of patients who underwent a posterior approach had improved
      recovery. CONCLUSIONS: Cervical IDH is a rare event, with this review of the
      literature outlining the clinical and radiographic parameters of its presentation
      as well as comparing common surgical strategies for treatment. We outline
      theories underlying the development of cervical IDH and argue for a posterior
      surgical approach in which the disc herniation is sequestrated with migration.

PMID- 29017983
TI  - Endoscopic Transsphenoidal Surgery Outcomes in 331 Nonfunctioning Pituitary
      Adenoma Cases After a Single Surgeon Learning Curve.
AB  - OBJECTIVE: The outcomes of recent endoscopic surgery of nonfunctioning pituitary
      adenomas (NFPAs) are controversial when compared with traditional microscopic
      surgery. We aimed to assess the outcomes of endoscopic transsphenoidal surgeries
      performed by 1 surgeon with 7 years of experience and elucidate the predictive
      factors for surgical outcomes for NFPAs. METHODS: We included 331 patients (155
      men and 176 women) with clinical NFPAs who underwent transsphenoidal surgery
      because of visual symptoms by a single surgeon in Seoul National University
      Hospital from March 2010 to May 2016. We assessed the tumor removal rate,
      hormonal outcomes, visual outcomes, and complications. RESULTS: The gross total
      resection rate of endoscopic transsphenoidal surgery for NFPAs by a single
      surgeon was 74.9%. Cavernous sinus invasion, a high Knosp grade, large tumor
      size, previous surgery, and lack of surgical experience in the neurosurgeon
      elevated the risk for residual tumors. Visual deficits were improved in 73.4% of
      the patients, which was associated with tumor size, preoperative visual
      impairment score, previous radiation, and surgical experience. Hormonal status
      was improved in 15.4% and aggravated in 32.9% after surgery. There were no
      predictors for hormonal recovery. Transient diabetes insipidus (DI) was the most
      common complication (9.1%), and among these patients, 3.0% had persistent DI.
      CONCLUSIONS: Endoscopic transsphenoidal surgery by a well-experienced surgeon was
      an effective and safe treatment for NFPAs, but the hormonal outcomes were not
      changed compared with previous reports of microscopic surgery. Large tumor size
      and cavernous sinus invasion were still the barriers for achieving total
      resection.

PMID- 29017984
TI  - Superficial Siderosis Associated with Pineal Cavernous Malformation.
AB  - BACKGROUND: Cavernous malformations in the pineal region are rare and difficult
      to anticipate from preoperative evaluation in patients with pineal apoplexy. We
      herein report the first case of a pineal cavernous malformation with superficial
      siderosis. Radiological findings were helpful in identifying the presence of the
      cavernous malformation. CASE DESCRIPTION: A 47-year-old female presented with a 4
      month history of progressive headache, nausea, and dizziness. She complained of
      double vision and exhibited upward gaze palsy and papilledema on fundoscopy.
      Radiological examination revealed subacute hemorrhage in the pineal region and
      enlarged lateral ventricles. Furthermore, T2-star-weighted gradient-echo magnetic
      resonance imaging demonstrated a linear hypointensity along the pial surface of
      the cerebral cortex, brainstem, and cerebellum, indicating hemosiderin deposition
      consistent with superficial siderosis. Suspecting the presence of a cavernous
      malformation based on the radiological findings of superficial siderosis, we
      performed total mass resection. The postoperative course was uneventful and her
      preoperative symptoms resolved completely. CONCLUSION: Radiological findings of
      superficial siderosis on T2-star-weighted gradient-echo imaging are useful to
      making a diagnosis of cavernous malformation in cases of pineal apoplexy. They
      are also important for making the treatment decision to perform total mass
      resection, which is the best curative method for pineal cavernous malformations.

PMID- 29017985
TI  - Analogous Three-Dimensional Constructive Interference in Steady State Sequences
      Enhance the Utility of Three-Dimensional Time of Flight Magnetic Resonance
      Angiography in Delineating Lenticulostriate Arteries in Insular Gliomas: Evidence
      from a Prospective Clinicoradiologic Analysis of 48 Patients.
AB  - BACKGROUND: Three-dimensional (3D) time of flight (TOF) imaging is the current
      gold standard for noninvasive, preoperative localization of lenticulostriate
      arteries (LSAs) in insular gliomas; however, the utility of this modality depends
      on tumor intensity. METHODS: Over a 3-year period, 48 consecutive patients with
      insular gliomas were prospectively evaluated. Location of LSAs and their
      relationship with the tumor were determined using a combination of contrast
      enhanced coronal 3D TOF magnetic resonance angiography and coronal 3D
      constructive interference in steady state (CISS) sequences. These findings were
      analyzed with respect to extent of tumor resection and early postoperative motor
      outcome. RESULTS: Tumor was clearly visualized in 29 (60.4%) patients with T1
      hypointense tumors using 3D TOF and in all patients using CISS sequences. Using
      combined 3D TOF and CISS, LSA-tumor interface was well seen in 47 patients,
      including all patients with T1-heterointense or T1-isointense tumors. Extent of
      resection was higher in the LSA-pushed group compared with the LSA-encased group.
      In the LSA-encased group, 6 (12.5%) patients developed postoperative hemiparesis;
      2 (4.2%) cases were attributed to LSA injury. CONCLUSIONS: Contrast-enhanced 3D
      TOF can delineate LSAs in almost all insular gliomas but is limited in
      identifying the LSA-tumor interface. This limitation can be overcome by addition
      of analogous CISS sequences that delineate the LSA-tumor interface regardless of
      tumor intensity. Combined 3D TOF and 3D CISS is a useful tool for surgical
      planning and safer resections of insular tumors and may have added surgical
      relevance when included as an intraoperative adjunct.

PMID- 29017986
TI  - Environmental Suitability of Vibrio Infections in a Warming Climate: An Early
      Warning System.
AB  - BACKGROUND: Some Vibrio spp. are pathogenic and ubiquitous in marine waters with
      low to moderate salinity and thrive with elevated sea surface temperature (SST).
      OBJECTIVES: Our objective was to monitor and project the suitability of marine
      conditions for Vibrio infections under climate change scenarios. METHODS: The
      European Centre for Disease Prevention and Control (ECDC) developed a platform
      (the ECDC Vibrio Map Viewer) to monitor the environmental suitability of coastal
      waters for Vibrio spp. using remotely sensed SST and salinity. A case-crossover
      study of Swedish cases was conducted to ascertain the relationship between SST
      and Vibrio infection through a conditional logistic regression. Climate change
      projections for Vibrio infections were developed for Representative Concentration
      Pathway (RCP) 4.5 and RCP 8.5. RESULTS: The ECDC Vibrio Map Viewer detected
      environmentally suitable areas for Vibrio spp. in the Baltic Sea in July 2014
      that were accompanied by a spike in cases and one death in Sweden. The estimated
      exposure-response relationship for Vibrio infections at a threshold of 16 degrees
      C revealed a relative risk (RR)=1.14 (95% CI: 1.02, 1.27; p=0.024) for a lag of 2
      wk; the estimated risk increased successively beyond this SST threshold. Climate
      change projections for SST under the RCP 4.5 and RCP 8.5 scenarios indicate a
      marked upward trend during the summer months and an increase in the relative risk
      of these infections in the coming decades. CONCLUSIONS: This platform can serve
      as an early warning system as the risk of further Vibrio infections increases in
      the 21st century due to climate change. https://doi.org/10.1289/EHP2198.

PMID- 29017988
TI  - Encouraging Physical Activity in Patients With Diabetes: Intervention Using a
      Reinforcement Learning System.
AB  - BACKGROUND: Regular physical activity is known to be beneficial for people with
      type 2 diabetes. Nevertheless, most of the people who have diabetes lead a
      sedentary lifestyle. Smartphones create new possibilities for helping people to
      adhere to their physical activity goals through continuous monitoring and
      communication, coupled with personalized feedback. OBJECTIVE: The aim of this
      study was to help type 2 diabetes patients increase the level of their physical
      activity. METHODS: We provided 27 sedentary type 2 diabetes patients with a
      smartphone-based pedometer and a personal plan for physical activity. Patients
      were sent short message service messages to encourage physical activity between
      once a day and once per week. Messages were personalized through a Reinforcement
      Learning algorithm so as to improve each participant's compliance with the
      activity regimen. The algorithm was compared with a static policy for sending
      messages and weekly reminders. RESULTS: Our results show that participants who
      received messages generated by the learning algorithm increased the amount of
      activity and pace of walking, whereas the control group patients did not.
      Patients assigned to the learning algorithm group experienced a superior
      reduction in blood glucose levels (glycated hemoglobin [HbA1c]) compared with
      control policies, and longer participation caused greater reductions in blood
      glucose levels. The learning algorithm improved gradually in predicting which
      messages would lead participants to exercise. CONCLUSIONS: Mobile phone apps
      coupled with a learning algorithm can improve adherence to exercise in diabetic
      patients. This algorithm can be used in large populations of diabetic patients to
      improve health and glycemic control. Our results can be expanded to other areas
      where computer-led health coaching of humans may have a positive impact. Summary
      of a part of this manuscript has been previously published as a letter in
      Diabetes Care, 2016.

PMID- 29017989
TI  - Uterine Fundectomy in Patients With Benign Etiology Undergoing Hysterectomy: New
      Surgical Technique.
AB  - BACKGROUND: Hysterectomy is the most common surgical procedure in gynecology, not
      only in cases of malignancies but also in many benign cases. Many uterine
      preservation techniques have been introduced as alternatives to hysterectomy.
      OBJECTIVE: We aimed to propose a new uterine surgical procedure. In this paper,
      we compare the utility of this new technique to the limitations of current
      procedures. METHODS: Uterine fundectomy may be considered as a subtotal
      hysterectomy. In this new technique, the uterine fundus including all pathologic
      tissue is cut as a reverse trapezoid by monopolar cautery. The upper side of the
      trapezoid, which includes the whole uterine fundus, is removed, but the fallopian
      tubes and cornual segment are preserved. A small uterine cavity remains, as well
      as the endometrial tissue lining it. RESULTS: Patient recruitment for this study
      began in April 2017 and is expected to end approximately 12 months later.
      Assessment of the primary outcomes is expected to take place in April 2018.
      CONCLUSIONS: Uterine preservation is particularly critical in developing new
      surgical approaches that can lead to a positive impact on patient satisfaction.
      This protocol outlines the first attempt to prospectively test surgical
      fundectomy in candidates for hysterectomy for benign indications.

PMID- 29017990
TI  - Healthy Beyond Pregnancy, a Web-Based Intervention to Improve Adherence to
      Postpartum Care: Randomized Controlled Feasibility Trial.
AB  - BACKGROUND: During the postpartum visit, health care providers address issues
      with short- and long-term implications for maternal and child health. Women with
      Medicaid insurance are less likely to return for a postpartum visit compared with
      women with private insurance. Behavioral economics acknowledges that people do
      not make exclusively rational choices, rather immediate gratification, cognitive
      and psychological biases, and social norms influence decision making. Drawing on
      insights from decision science, behavioral economists have examined how these
      biases can be modulated through carefully designed interventions. We have
      developed a Web-based tool, Healthy Beyond Pregnancy, that incorporates
      empirically derived concepts of behavioral economics to improve adherence rates
      to the postpartum visit. OBJECTIVES: The primary objectives of this pilot study
      were to (1) refine and assess the usability of Healthy Beyond Pregnancy and (2)
      assess the feasibility of a randomized controlled trial (RCT) of the
      intervention. METHODS: We used a multistep process and multidisciplinary team of
      maternal-fetal medicine physicians, a behavioral economist, and researchers with
      expertise in behavioral interventions to design Healthy Beyond Pregnancy. We
      assessed the usability of the program with the Post-Study System Usability
      Questionnaire (PSSUQ), a validated 7-point scale, and semistructured interviews
      with postpartum women. We then conducted a feasibility trial to determine the
      proportion of eligible women who were willing to participate in an RCT of Healthy
      Beyond Pregnancy and the proportion of women willing to complete the Web-based
      program. Exploratory outcomes of the pilot trial included attendance at the
      postpartum visit, uptake of long-acting reversible contraception, and uptake of
      any contraception. RESULTS: The median PSSUQ score for Healthy Beyond Pregnancy
      was 6.5 (interquartile range: 6.1-7) demonstrating high usability. Semistructured
      interviews (n=10) provided in-depth comments about users' experience and further
      improved the program. A total of 34 postpartum women with Medicaid insurance were
      approached for the pilot trial, and 30 (88%) were consented and randomized. All
      women randomized to Healthy Beyond Pregnancy completed the Web-based program, had
      text-enabled cell phones, and were willing to receive text messages from the
      study team. Women in the Healthy Beyond Pregnancy arm were more likely to return
      for a postpartum visit compared with women in the control arm with 85% of women
      in Healthy Beyond Pregnancy returning versus 53% in the control arm (odds ratio
      in the Healthy Beyond Pregnancy group: 5.3; 95% CI 0.9-32.0; P=.06). CONCLUSIONS:
      We have developed a highly usable and acceptable Web-based program designed to
      increase attendance at the postpartum visit. Our pilot trial demonstrates that
      women are willing and able to participate in a randomized trial of a Web-based
      program and text messaging system. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT03296774; https://clinicaltrials.gov/ct2/show/NCT03296774 (Archived by WebCite
      at http://www.webcitation.org/6tpgXFzyk).

PMID- 29017992
TI  - Mobile Apps for Suicide Prevention: Review of Virtual Stores and Literature.
AB  - BACKGROUND: The best manner to prevent suicide is to recognize suicidal signs and
      signals, and know how to respond to them. OBJECTIVE: We aim to study the existing
      mobile apps for suicide prevention in the literature and the most commonly used
      virtual stores. METHODS: Two reviews were carried out. The first was done by
      searching the most commonly used commercial app stores, which are iTunes and
      Google Play. The second was a review of mobile health (mHealth) apps in published
      articles within the last 10 years in the following 7 scientific databases:
      Science Direct, Medline, PsycINFO, Embase, The Cochrane Library, IEEE Xplore, and
      Google Scholar. RESULTS: A total of 124 apps related to suicide were found in the
      cited virtual stores but only 20 apps were specifically designed for suicide
      prevention. All apps were free and most were designed for Android. Furthermore, 6
      relevant papers were found in the indicated scientific databases; in these
      studies, some real experiences with physicians, caregivers, and families were
      described. The importance of these people in suicide prevention was indicated.
      CONCLUSIONS: The number of apps regarding suicide prevention is small, and there
      was little information available from literature searches, indicating that
      technology-based suicide prevention remains understudied. Many of the apps
      provided no interactive features. It is important to verify the accuracy of the
      results of different apps that are available on iOS and Android. The confidence
      generated by these apps can benefit end users, either by improving their health
      monitoring or simply to verify their body condition.

PMID- 29017995
TI  - Germline Testing Could Help More Patients.
AB  - In addition to tumor sequencing for targetable somatic alterations, patients with
      cancer may benefit from concurrent germline analysis, which increases the
      discovery of clinically actionable mutations, according to a recent study.

PMID- 29017991
TI  - Feasibility of Gamified Mobile Service Aimed at Physical Activation in Young Men:
      Population-Based Randomized Controlled Study (MOPO).
AB  - BACKGROUND: The majority of young people do not meet the recommendations on
      physical activity for health. New innovative ways to motivate young people to
      adopt a physically active lifestyle are needed. OBJECTIVE: The study aimed to
      study the feasibility of an automated, gamified, tailored Web-based mobile
      service aimed at physical and social activation among young men. METHODS: A
      population-based sample of 496 young men (mean age 17.8 years [standard deviation
      0.6]) participated in a 6-month randomized controlled trial (MOPO study).
      Participants were randomized to an intervention (n=250) and a control group
      (n=246). The intervention group was given a wrist-worn physical activity monitor
      (Polar Active) with physical activity feedback and access to a gamified Web-based
      mobile service, providing fitness guidelines, tailored health information, advice
      of youth services, social networking, and feedback on physical activity. Through
      the trial, the physical activity of the men in the control group was measured
      continuously with an otherwise similar monitor but providing only the time of day
      and no feedback. The primary outcome was the feasibility of the service based on
      log data and questionnaires. Among completers, we also analyzed the change in
      anthropometry and fitness between baseline and 6 months and the change over time
      in weekly time spent in moderate to vigorous physical activity. RESULTS: Mobile
      service users considered the various functionalities related to physical activity
      important. However, compliance of the service was limited, with 161 (64.4%,
      161/250) participants visiting the service, 118 (47.2%, 118/250) logging in more
      than once, and 41 (16.4%, 41/250) more than 5 times. Baseline sedentary time was
      higher in those who uploaded physical activity data until the end of the trial
      (P=.02). A total of 187 (74.8%, 187/250) participants in the intervention and 167
      (67.9%, 167/246) in the control group participated in the final measurements.
      There were no differences in the change in anthropometry and fitness from
      baseline between the groups, whereas waist circumference was reduced in the most
      inactive men within the intervention group (P=.01). Among completers with valid
      physical activity data (n=167), there was a borderline difference in the change
      in mean daily time spent in moderate to vigorous physical activity between the
      groups (11.9 min vs -9.1 min, P=.055, linear mixed model). Within the
      intervention group (n=87), baseline vigorous physical activity was inversely
      associated with change in moderate to vigorous physical activity during the trial
      (R=-.382, P=.01). CONCLUSIONS: The various functionalities related to physical
      activity of the gamified tailored mobile service were considered important.
      However, the compliance was limited. Within the current setup, the mobile service
      had no effect on anthropometry or fitness, except reduced waist circumference in
      the most inactive men. Among completers with valid physical activity data, the
      trial had a borderline positive effect on moderate to vigorous physical activity.
      Further development is needed to improve the feasibility and adherence of an
      integrated multifunctional service. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT01376986; http://clinicaltrials.gov/ct2/show/NCT01376986 (Archived by WebCite
      at http://www.webcitation.org/6tjdmIroA).

PMID- 29017994
TI  - Utilizing Consumer Health Informatics to Support Management of Hypertension by
      Clinical Pharmacists in Primary Care: Study Protocol.
AB  - BACKGROUND: Hypertension (HTN) is a major public health concern in the United
      States given its wide prevalence, high cost, and poor rates of control. Multiple
      strategies to counter this growing epidemic have been studied, and home blood
      pressure (BP) monitoring, mobile health (mHealth) interventions, and referrals to
      clinical pharmacists for BP management have all shown potential to be effective
      intervention strategies. OBJECTIVE: The purpose of this study is to establish
      feasibility and acceptability of BPTrack, a clinical pharmacist-led mHealth
      intervention that aims to improve BP control by supporting home BP monitoring and
      medication adherence among patients with uncontrolled HTN. BPTrack is an
      intervention that makes home-monitored BP data available to clinical pharmacists
      for use in HTN management. Secondarily, this study seeks to understand barriers
      to adoption of this intervention, as well as points of improvement among key
      stakeholders, so that larger scale dissemination of the intervention may be
      achieved and more rigorous research can be conducted. METHODS: This study is
      recruiting up to 25 individuals who have poorly controlled HTN from a Family
      Medicine clinic affiliated with a large Midwestern academic medical center.
      Patient participants complete a baseline visit, including installation and
      instructions on how to use BPTrack. Patient participants are then asked to follow
      the BP monitoring protocol for a period of 12 weeks, and subsequently complete a
      follow-up visit at the conclusion of the study period. RESULTS: The recruitment
      period for the pilot study began in November 2016, and data collection is
      expected to conclude in late-2017. CONCLUSIONS: This pilot study seeks to
      document the feasibility and acceptability of a clinical pharmacist-led mHealth
      approach to managing HTN within a primary care setting. Through our 12-week pilot
      study, we expect to lend support for this approach, and lay the foundation for
      translating this approach into wider-scale implementation. This mHealth
      intervention seeks to leverage the multidisciplinary care team already in place
      within primary care, and to improve health outcomes for patients with
      uncontrolled HTN. TRIAL REGISTRATION: Clinicaltrials.gov NCT02898584;
      https://clinicaltrials.gov/ct2/show/NCT02898584 (Archived by WebCite(r) at
      http://www.webcitation.org/6u3wTGbe6).

PMID- 29017993
TI  - Views of Community Managers on Knowledge Co-creation in Online Communities for
      People With Disabilities: Qualitative Study.
AB  - BACKGROUND: The use of online communities to promote end user involvement and co
      creation in the product and service innovation process is well documented in the
      marketing and management literature. Whereas online communities are widely used
      for health care service provision and peer-to-peer support, only little is known
      about how they could be integrated into the health care innovation process.
      OBJECTIVE: The overall objective of this qualitative study was to explore
      community managers' views on and experiences with knowledge co-creation in online
      communities for people with disabilities. METHODS: A descriptive qualitative
      research design was used. Data were collected through semi-structured interviews
      with nine community managers. To complement the interview data, additional
      information was retrieved from the communities in the form of structural
      information (number of registered users, number and names of topic areas covered
      by the forum) and administrative information (terms and conditions and privacy
      statements, forum rules). Data were analyzed using thematic analysis. RESULTS:
      Our results highlight two main aspects: peer-to-peer knowledge co-creation and
      types of collaboration with external actors. Although community managers strongly
      encouraged peer-to-peer knowledge co-creation, our findings indicated that these
      activities were not common practice in the communities under investigation. In
      fact, much of what related to co-creation, prototyping, and product development
      was still perceived to be directed by professionals and experts. Community
      managers described the role of their respective communities as informing this
      process rather than a driving force. The role of community members as advisors to
      researchers, health care professionals, and businesses was discussed in the
      context of types of collaboration with external actors. According to the
      community managers, most of the external inquiries related to research projects
      of students or health care professionals in training, who often joined a
      community for the sole purpose of recruiting participants for their research.
      Despite this unilateral form of knowledge co-creation, community managers
      acknowledged the mere interest of these user groups as beneficial, as long as
      their interest was not purely financially motivated. Being able to contribute to
      advancing research, improving products, and informing the planning and design of
      health care services were described as some of the key motivations to engage with
      external stakeholders. CONCLUSIONS: This paper draws attention to the currently
      under-investigated role of online communities as platforms for collaboration and
      co-creation between patients, health care professionals, researchers, and
      businesses. It describes community managers' views on and experiences with
      knowledge co-creation and provides recommendations on how these activities can be
      leveraged to foster knowledge co-creation in health care. Engaging in knowledge
      co-creation with online health communities may ultimately help to inform the
      planning and design of products, services, and research activities that better
      meet the actual needs of those living with a disability.

PMID- 29017987
TI  - Nanomaterials Versus Ambient Ultrafine Particles: An Opportunity to Exchange
      Toxicology Knowledge.
AB  - BACKGROUND: A rich body of literature exists that has demonstrated adverse human
      health effects following exposure to ambient air particulate matter (PM), and
      there is strong support for an important role of ultrafine (nanosized) particles.
      At present, relatively few human health or epidemiology data exist for engineered
      nanomaterials (NMs) despite clear parallels in their physicochemical properties
      and biological actions in in vitro models. OBJECTIVES: NMs are available with a
      range of physicochemical characteristics, which allows a more systematic
      toxicological analysis. Therefore, the study of ultrafine particles (UFP, <100 nm
      in diameter) provides an opportunity to identify plausible health effects for
      NMs, and the study of NMs provides an opportunity to facilitate the understanding
      of the mechanism of toxicity of UFP. METHODS: A workshop of experts
      systematically analyzed the available information and identified 19 key lessons
      that can facilitate knowledge exchange between these discipline areas.
      DISCUSSION: Key lessons range from the availability of specific techniques and
      standard protocols for physicochemical characterization and toxicology assessment
      to understanding and defining dose and the molecular mechanisms of toxicity. This
      review identifies a number of key areas in which additional research
      prioritization would facilitate both research fields simultaneously. CONCLUSION:
      There is now an opportunity to apply knowledge from NM toxicology and use it to
      better inform PM health risk research and vice versa.
      https://doi.org/10.1289/EHP424.

PMID- 29017996
TI  - Sperm counts, testicular cancers, and the environment.

PMID- 29017997
TI  - Population-Based Study on Patterns of Cardiac Stress Testing After Percutaneous
      Coronary Intervention.
AB  - BACKGROUND: The appropriate use criteria considers cardiac stress testing within
      2 years after percutaneous coronary intervention (PCI) to be rarely appropriate,
      unless prompted by symptoms or change in clinical status. Little is known about
      the patterns of cardiac stress testing after PCI in the single-payer Canadian
      healthcare system, where mechanisms for reimbursement are different from the
      United States. METHODS AND RESULTS: Frequency and timing of cardiac stress
      testing within 2 years of PCI performed between April 2004 and March 2013 in
      Ontario, Canada, was determined from linked provincial databases. Subsequent
      rates of coronary angiography and revascularization after stress testing were
      ascertained. Of the 112 691 patients with PCI, 67 442 (59.8%) underwent at least
      1 stress test, with 38 267 (34.0%) undergoing repeat stress testing (ie, >1
      stress test) within 2 years. Patients who underwent stress testing were younger,
      had less medical comorbidities, were more likely to reside in urban areas, and
      had higher incomes. Spikes in incidence of repeat stress testing were observed at
      3 to 4 months, 6 to 7 months, and 12 to 13 months after the prior stress test. Of
      those tested, only 5.9% underwent subsequent coronary angiography, and only 3.1%
      underwent repeat revascularization within 60 days of stress testing. CONCLUSIONS:
      More than half of all patients undergo cardiac stress testing within 2 years of
      PCI, with one third undergoing repeat stress tests. Only 1 of 30 tested patients
      underwent repeat revascularization. These findings reinforce the appropriate use
      criteria recommendations against routine stress testing after PCI. Further work
      is needed to aid with the selection of patients most likely to benefit from
      stress testing after PCI.

PMID- 29017998
TI  - Making a Difference in Disparities.

PMID- 29017999
TI  - Erratum. Genetic Disruption of Adenosine Kinase in Mouse Pancreatic beta-Cells
      Protects Against High-Fat Diet-Induced Glucose Intolerance. Diabetes 2017;66:1928
      1938.

PMID- 29018000
TI  - Waveform capnography: an alternative to physician gestalt in determining optimal
      intubating conditions after administration of paralytic agents.
AB  - PURPOSE: We sought to evaluate the utility of waveform capnography (WC) in
      detecting paralysis, by using apnoea as a surrogate determinant, as compared with
      clinical gestalt during rapid sequence intubation. Additionally, we sought to
      determine if this improves the time to intubation and first pass success rates
      through more consistent and expedient means of detecting optimal intubating
      conditions (ie, paralysis). METHODS: A prospective observational cohort study of
      consecutively enrolled patients was conducted from April to June 2016 at an
      academic, urban, level 1 trauma centre in New York City. Nasal cannula WC was
      used to determine the presence of apnoea as a surrogate measure of paralysis
      versus physician gestalt (ie, blink test, mandible relaxation, and so on).
      RESULTS: One hundred patients were enrolled (50 in the WC group and 50 in the
      gestalt group). There were higher proportions of failure to determine optimal
      intubating conditions (ie, paralysis) in the gestalt group (32%, n=16) versus the
      WC group (6%, n=3), absolute difference 26, 95% CI 10 to 40. Time to intubation
      was longer in the gestalt group versus the WC group (136 seconds vs 116 seconds,
      absolute difference 20 seconds 95% CI 14 to 26). First pass success rates were
      higher in the WC group verses the gestalt group (92%, 95% CI 85 to 97 vs 88%, 95%
      CI 88 to 95, absolute difference 4%, 95% CI 1 to 8). CONCLUSION: These
      preliminary results demonstrate WC may be a useful objective measure to determine
      the presence of paralysis and optimal in tubating conditions in RSI.

PMID- 29018001
TI  - Quality of care is under threat, and services "straining at the seams," warns
      CQC.

PMID- 29018002
TI  - Glucose uptake inhibition decreases expressions of receptor activator of nuclear
      factor-kappa B ligand (RANKL) and osteocalcin in osteocytic MLO-Y4-A2 cells.
AB  - Bone and glucose metabolism are closely associated with each other. Both
      osteoblast and osteoclast functions are important for the action of osteocalcin,
      which plays pivotal roles as an endocrine hormone regulating glucose metabolism.
      However, it is unknown whether osteocytes are involved in the interaction between
      bone and glucose metabolism. We used MLO-Y4-A2, a murine long bone-derived
      osteocytic cell line, to investigate effects of glucose uptake inhibition on
      expressions of osteocalcin and bone-remodeling modulators in osteocytes. We found
      that glucose transporter 1 (GLUT1) is expressed in MLO-Y4-A2 cells and that
      treatment with phloretin, a GLUT inhibitor, significantly inhibited glucose
      uptake. Real-time PCR and Western blot showed that phloretin significantly and
      dose-dependently decreased the expressions of RANKL and osteocalcin, whereas
      osteoprotegerin or sclerostin was not affected. Moreover, phloretin activated AMP
      activated protein kinase (AMPK), an intracellular energy sensor. Coincubation of
      ara-A, an AMPK inhibitor, with phloretin canceled the phloretin-induced decrease
      in osteocalcin expression, but not RANKL. In contrast, phloretin suppressed
      phosphorylation of ERK1/2, JNK, and p38 MAPK, and treatments with the p38
      inhibitor SB203580 and the MEK inhibitor PD98059, but not the JNK inhibitor
      SP600125, significantly decreased expressions of RANKL and osteocalcin. These
      results indicate that glucose uptake by GLUT1 is required for RANKL and
      osteocalcin expressions in osteocytes, and that inhibition of glucose uptake
      decreases their expressions through AMPK, ERK1/2, and p38 MAPK pathways. These
      findings suggest that lowering glucose uptake into osteocytes may contribute to
      maintain blood glucose levels by decreasing osteocalcin expression and RANKL
      induced bone resorption.

PMID- 29018003
TI  - Improving patient outcomes after surgery.

PMID- 29018004
TI  - Mid-Upper-Arm Circumference and Arm-to-Height Ratio to Identify Obesity in School
      Age Children.
AB  - BACKGROUND: In resource-poor settings, anthropometric parameters are evaluated as
      potential alternatives to the body mass index (BMI) for detecting overweight and
      obesity in children. To this end, the mid-upper-arm circumference (MUAC) and the
      mid-upper-arm circumference-to-height ratio (AHtR) were evaluated as proxies to
      BMI in Thai school-age children. STUDY DESIGN: An observational, cross-sectional
      study was performed on school-aged children. PARTICIPANTS: Children in grades 1
      through 6 at all public elementary schools in the Ongkharak district, Nakhon
      Nayok, Thailand during May and June 2013 were included. This is a rural district
      with low per capita income. METHODS: Weight, height, and MUAC were measured in
      school-age children and analyzed to identify optimal cut-off values for MUAC and
      AHtR for detection of overweight and obesity in comparison to BMI. Receiver
      operating characteristic (ROC) curve analysis determined the validity of MUAC and
      AHtR use. RESULTS: Data from 3,618 children, aged 6.0-12.99 years, were analyzed.
      MUAC correlated with age and height (P < 0.001), but especially with body weight
      (r = 0.888 to 0.914) and BMI (r = 0.859 to 0.908) in both genders, while AHtR
      correlated with body weight and BMI (P < 0.001), but not with age. Cut-off values
      of MUAC for obesity diagnosis ranged from 18.9 to 25.5 cm for boys and from 19.8
      to 25.4 cm for girls. Accuracy was excellent for both boys (AUC = 0.952-0.991)
      and girls (AUC = 0.917-0.990). Cut-off of MUAC for overweight diagnosis ranged
      from 17.2 to 22.4 cm for boys (AUC = 0.883-0.965) and from 18.0 to 23.2 cm for
      girls (AUC = 0.905-0.931). AHtR cut-off values for obesity and overweight
      diagnosis at 0.16 and 0.145, respectively, were determined with excellent
      diagnostic accuracy (AUC ranged from 0.920 to 0.975). CONCLUSION: MUAC and AHtR
      were reliable tools to detect overweight and obesity in Thai school-age children.
      Cut-off points for MUAC were age and gender specific, while AHtR at 0.16 and
      0.145 were the optimal values for both genders, independent of age. These
      anthropometric measurements showed excellent accuracy in predicting overweight
      and obesity with high specificity and sensitivity.

PMID- 29018005
TI  - The Clinical Presentation of Subcutaneous Phaeohyphomycosis: A Case Series from
      Yetebon, Ethiopia.
AB  - Subcutaneous phaeohyphomycosis is a chronic fungal infection usually found on the
      lower extremity and feet of agricultural workers in the tropics. It can present
      with various skin manifestations, verrucous to nodular plaques, and is caused by
      multiple species of fungi. Laboratory confirmation requires skin samples for
      pathology and fungal cultures. Cure, often difficult in resource-poor countries,
      requires months of antifungal therapy. We describe the cases of three men from
      Ethiopia who were seen and are being treated by American doctors who traveled
      there on a medical mission.

PMID- 29018007
TI  - Clinical Characteristics of the GLA N215S Variant and Implications for the
      Diagnosis and Management of Nonclassic Fabry Disease.

PMID- 29018006
TI  - alpha-Galactosidase A Genotype N215S Induces a Specific Cardiac Variant of Fabry
      Disease.
AB  - BACKGROUND: Hypertrophic cardiomyopathy is the most common type of
      cardiomyopathy, but many patients lack sarcomeric/myofilament mutations. We
      studied whether cardio-specific alpha-galactosidase A gene variants are
      misinterpreted as hypertrophic cardiomyopathy because of the lack of extracardiac
      organ involvement. METHODS AND RESULTS: All subjects who tested positive for the
      N215S genotype (n=26, 13 females, mean age 49+/-17 [range, 14-74] years) were
      characterized in this prospective monocentric longitudinal cohort study to
      determine genotype-specific clinical characteristics of the N215S (c.644A>G
      [p.Asn215Ser]) alpha-galactosidase A gene variant. All subjects were initially
      referred with suspicion of genetically determined hypertrophic cardiomyopathy.
      Cardiac hypertrophy (interventricular septum, 12+/-4 [7-23] mm; left ventricular
      posterior wall, 11+/-4 [7-21] mm; left ventricular mass, 86+/-41 [46-195] g/m2)
      was progressive, systolic function mainly preserved (cardiac index 2.8+/-0.6 [1.9
      3.9] L/min per m2), and diastolic function mildly abnormal. Cardiac magnetic
      resonance imaging revealed replacement fibrosis in loco typico (18/26, 69%),
      particularly in subjects >50 years. Elderly subjects had advanced heart failure,
      and 6 (23%) were suggested for implantable cardioverter-defibrillator therapy.
      Leukocyte alpha-galactosidase A enzyme activity was mildly reduced in 19 subjects
      and lyso-globotriaosylceramide slightly elevated (median, 4.9; interquartile
      range, 1.3-9.1 ng/mL). Neurological and renal impairments (serum creatinine,
      0.87+/-0.20; median, 0.80; interquartile range, 0.70-1.01 mg/dL; glomerular
      filtration rate, 102+/-23; median, 106; interquartile range, 84-113 mL/min) were
      discreet. Only 2 subjects developed clinically relevant proteinuria. CONCLUSIONS:
      alpha-Galactosidase A genotype N215S does not lead to the development of a
      classical Fabry phenotype but induces a specific cardiac variant of Fabry disease
      mimicking nonobstructive hypertrophic cardiomyopathy. The lack of prominent
      noncardiac impairment leads to a significant delay in diagnosis and Fabry
      specific therapy.

PMID- 29018008
TI  - Comparison of postoperative outcomes among patients treated by male and female
      surgeons: a population based matched cohort study.
AB  - Objective To examine the effect of surgeon sex on postoperative outcomes of
      patients undergoing common surgical procedures.Design Population based,
      retrospective, matched cohort study from 2007 to 2015.Setting Population based
      cohort of all patients treated in Ontario, Canada.Participants Patients
      undergoing one of 25 surgical procedures performed by a female surgeon were
      matched by patient age, patient sex, comorbidity, surgeon volume, surgeon age,
      and hospital to patients undergoing the same operation by a male
      surgeon.Interventions Sex of treating surgeon.Main outcome measure The primary
      outcome was a composite of death, readmission, and complications. We compared
      outcomes between groups using generalised estimating equations.Results 104 630
      patients were treated by 3314 surgeons, 774 female and 2540 male. Before
      matching, patients treated by female doctors were more likely to be female and
      younger but had similar comorbidity, income, rurality, and year of surgery. After
      matching, the groups were comparable. Fewer patients treated by female surgeons
      died, were readmitted to hospital, or had complications within 30 days (5810 of
      52 315, 11.1%, 95% confidence interval 10.9% to 11.4%) than those treated by male
      surgeons (6046 of 52 315, 11.6%, 11.3% to 11.8%; adjusted odds ratio 0.96, 0.92
      to 0.99, P=0.02). Patients treated by female surgeons were less likely to die
      within 30 days (adjusted odds ratio 0.88; 0.79 to 0.99, P=0.04), but there was no
      significant difference in readmissions or complications. Stratified analyses by
      patient, physician, and hospital characteristics did not significant modify the
      effect of surgeon sex on outcome. A retrospective analysis showed no difference
      in outcomes by surgeon sex in patients who had emergency surgery, where patients
      do not usually choose their surgeon.Conclusions After accounting for patient,
      surgeon, and hospital characteristics, patients treated by female surgeons had a
      small but statistically significant decrease in 30 day mortality and similar
      surgical outcomes (length of stay, complications, and readmission), compared with
      those treated by male surgeons. These findings support the need for further
      examination of the surgical outcomes and mechanisms related to physicians and the
      underlying processes and patterns of care to improve mortality, complications,
      and readmissions for all patients.

PMID- 29018009
TI  - Paediatric case of ductal origin of right pulmonary artery presenting with
      exertional dyspnoea and mimicking asthma and primary ciliary dyskinesia.
AB  - Ductal origin of pulmonary artery is a rare anomaly that is frequently
      misdiagnosed. Patients may present with exertional dyspnoea, recurrent
      respiratory infections and pulmonary hypertension. The presence of pulmonary
      hypertension can adversely affect clinical outcome in these patients; hence,
      early identification and intervention is the key to improve survival. A case of a
      3-year-old child presenting with exertional dyspnoea is presented in this report.
      Chest radiograph revealed right-sided pulmonary hypoplasia and mediastinal shift
      to the right. Pulmonary artery agenesis was suspected when CT of the chest
      demonstrated right-sided pulmonary artery agenesis. Cardiac catheterisation
      revealed the correct diagnosis of ductal origin of right pulmonary artery. The
      most striking feature of this case is that the clinical presentation is mild
      compared with the findings on imaging.

PMID- 29018010
TI  - Unusual complications from amitriptyline intoxication.
AB  - Althoughtricyclic antidepressants(TCAs) are frequently prescribed to patients
      with depression, these drugs can also be misused. A 21-year-old comatose patient
      was referred to our hospital presenting with ventricular tachycardia. Despite
      initial treatment including intravascular lipid emulsion, ventricular
      fibrillation occurred soon after arrival. Venoarterial extracorporeal membrane
      oxygenation and therapeutic hypothermia were administered. Refractory arrhythmia
      disappeared on the next day. A high concentration of amitriptyline was identified
      in his blood samples on arrival. Mechanical bowel obstruction followed after
      abdominal compartment syndrome caused by anticholinergic effects, and refractory
      seizure occurred due to TCA intoxication. Although seizure was brought under
      control with anticonvulsant agents, his Glasgow Coma Scale did not recover to the
      full score. MRI presented irreversible damage to the bilateral frontal lobe and
      insula. Amitriptyline has the potential to cause unusual serious complications,
      such as abdominal compartment syndrome, irreversible central nervous system
      disability and lethal arrhythmia.

PMID- 29018011
TI  - Balance versus hearing after cochlear implant in an adult.
AB  - The effect of vestibular rehabilitation (VR) on anxiety, dizziness and poor
      balance that developed after cochlear implant (CI) surgery is described. A 54
      year-old woman, with profound hearing loss since the age of 2 years, underwent
      right CI surgery 2 years previously. On implant activation, the patient
      immediately felt dizziness and imbalance, which affected the ability to perform
      activities of daily living and increased anxiety to where the patient considered
      the CI removal. Prior to VR the patient was evaluated with the Dizziness Handicap
      Inventory and the Visual Vertigo Dizziness Questionnaire and clinically with the
      Zur Balance Scale and Video Head Impulse Test. The patient underwent 14 VR
      sessions over 4 months that included compensation, adaptation and habituation
      exercises. After VR the patient was able to maintain good balance while using the
      CI. Dizziness and anxiety improved dramatically. This report increases awareness
      that a CI could compromise balance, which can be overcome with personalised VR.

PMID- 29018012
TI  - Colonic gallstone ileus.
AB  - Gallstone ileus is a rare aetiology of bowel obstruction and very infrequently
      occurs in the colon. Typically, colonic gallstone ileus carries a high morbidity
      and mortality and requires surgery. This case report describes a
      cholecystocolonic fistula in a patient with ulcerative colitis with resulting
      colonic gallstone ileus, which was successfully intervened on via an endoscopic
      approach.

PMID- 29018013
TI  - Stroke resulting from an isolated pulmonary arteriovenous malformation.
AB  - Isolated pulmonary arteriovenous malformations (PAVM) are rare, but can be
      responsible for paradoxical embolic events. It is important to recognise these
      situations early and intervene quickly to attain the best outcome. We describe
      the case of a 45-year-old woman with a long-standing history of migraines with
      aura who presented to the emergency department with left-sided weakness and
      slurred speech. Work-up was unclear and she was diagnosed with cryptogenic
      stroke. Follow-up transoesophageal echocardiogram was suggestive of an atrial
      septal defect, though no clear defect was evident. Pulmonary angiography revealed
      an isolated PAVM arising from the right lower lung segmental artery with a 2 mm
      feeding artery leading into 3-4 mm of dysplastic vessel that connects to the
      vein. The vessel was embolised successfully using a combination of a 4 mm
      Amplatzer Vascular Plug in the distal feeding artery and a 4 mm Nester coil
      proximally.

PMID- 29018014
TI  - Elizabethkingia meningoseptica: emerging multidrug resistance in a nosocomial
      pathogen.
AB  - A 46-year-old male patient presented with complaints of burning micturition for 2
      days. Initial history, physical examination and laboratory investigations were
      consistent with the diagnosis of congestive cardiac failure (CCF) and concomitant
      urinary tract infection. CCF was treated with diuretics and a urine
      culture/sensitivity (C/S) was sent which returned growing Elizabethkingia
      meningoseptica resistant to all tested drugs. Intravenous cefotaxime which had
      been started empirically 3 days earlier was withheld at this point, and a repeat
      urine C/S was sent revealing resistance to all tested drugs (including reserved
      drugs) barring minocycline. The patient was treated with oral minocycline for 14
      days after which he was symptomatically better with sterile urine. The patient
      was subsequently discharged.

PMID- 29018015
TI  - Chronic red eye: a masquerade of advanced neoplastic disease.
AB  - A 42-year-old woman presented with chronic history of left red eye for more than
      12 months, treated with difference topical medication but without response.
      Ocular external examination demonstrated a firm palpable mass in the medial
      portion of the lower eyelid and slit-lamp evaluation of the lesion showed an
      ulcerated conjunctival nodule, keratin secretor. CT of the orbits revealed left
      sided orbital mass located anteriorly, inferiorly and medially in the orbit,
      adjacent to the globe and orbit walls. Incisional biopsy of the lesion was
      consistent with invasive squamous cell carcinoma of the conjunctiva. As the
      tumour had no response to initial adjuvant systemic chemotherapy, exenteration of
      left orbit was performed due to advanced disease.

PMID- 29018016
TI  - Successful treatment of community-acquired methicillin-resistant Staphylococcus
      aureus purulent myopericarditis.
AB  - A previously healthy 48-year-old active duty man, who had been treated for an
      elbow abscess 3 weeks earlier, presented to an emergency department in Bahrain
      with tachycardia, pericardial friction rub and jugular venous distention. Cardiac
      tamponade was confirmed on transthoracic echocardiogram and he was taken for
      emergent pericardiocentesis. Pericardial fluid cultures grew community-acquired
      methicillin-resistant Staphylococcus aureus Despite ongoing treatment with
      intravenous vancomycin, he developed a recurrent fibrinous pericardial effusion
      and constrictive pericarditis requiring pericardiectomy. Though he initially did
      well postoperatively, he developed drug reaction with eosinophilia and systemic
      symptoms syndrome in response to vancomycin. He was transitioned to ceftaroline
      and started on high-dose steroids. He recovered during a week-long admission and
      was discharged home. Several weeks later at follow-up he was doing well and had
      resumed moderate intensity exercise.

PMID- 29018017
TI  - Radial nerve palsy due to supracondylar open fracture in a child.

PMID- 29018018
TI  - Acute pancreatitis as an unusual presentation of primary splenic lymphoma.
AB  - A 51-year-old man with no relevant medical history presents to the emergency
      department complaining of a recent worsening of few months upper abdominal pain
      with back radiation and postprandial fullness, without B symptoms. Laboratory
      analysis showed hyperamylasaemia, elevated lactate dehydrogenase and inflammatory
      parameters. Abdominal ultrasonography revealed a heterogeneous solid mass in the
      spleen/splenic hilum with pancreatic parenchyma continuity and no biliary tract
      dilation or gallstones. A mild acalculous acute pancreatitis diagnosis was made.
      Abdominopelvic CT revealed a large heterogeneous mass infiltrating the spleen and
      pancreas and obstructing the common bile duct at the pancreatic level with
      upstream dilation of biliary and pancreatic ducts, with splenic vein invasion.
      Several necrotic, peripancreatic and hepatic hilar adenopathies were also
      observed. Ultrasound-guided biopsy showed a primary splenic diffuse large B-cell
      non-Hodgkin's lymphoma. Chemotherapy with R-CHOP (rituximab, cyclophosphamide,
      doxorubicin, vincristine and prednisolone) was performed with lack of response
      and the patient died within 10 months of diagnosis onset.

PMID- 29018019
TI  - There's no such thing as an unnecessary referral.

PMID- 29018020
TI  - Relation of Low-Density Lipoprotein Cholesterol With Microvascular Injury and
      Clinical Outcome in Revascularized ST-Elevation Myocardial Infarction.
AB  - BACKGROUND: Microvascular injury (MVI) after primary percutaneous coronary
      intervention for ST-elevation myocardial infarction (STEMI) is a major
      determinant of adverse clinical outcome. Experimental data indicate an impact of
      hypercholesterolemia on MVI; however, there is a lack of clinical studies
      confirming this relation. We aimed to investigate the association of cholesterol
      concentrations on admission with MVI visualized by cardiac magnetic resonance
      imaging and clinical outcome in STEMI patients treated by primary percutaneous
      coronary intervention. METHODS AND RESULTS: In this prospective, observational
      study, we included 235 consecutive revascularized STEMI patients. Cholesterol
      (total cholesterol, low-density lipoprotein [LDL], and high-density lipoprotein
      cholesterol) and triglyceride concentrations were determined at presentation.
      Cardiac magnetic resonance scans were performed 2 (2-4) days after infarction to
      assess infarct characteristics, including MVI. Clinical end point was the
      occurrence of major adverse cardiac events (MACE) comprising all-cause mortality,
      nonfatal reinfarction, and new congestive heart failure. Patients with MVI
      (n=129; 55%) showed higher levels of total cholesterol (204 [172-226] versus 185
      [168-212] mg/dL; P=0.01) and LDL cholesterol (142 [113-166] versus 118 [103-149]
      mg/dL; P=0.001), whereas high-density lipoprotein cholesterol and triglycerides
      did not differ significantly. In multivariable analysis, including all
      significant clinical and cardiac magnetic resonance determinants of MVI, LDL
      concentration emerged as an independent predictor of MVI (odds ratio, 1.02 [95%
      confidence interval, 1.01-1.02]; P=0.002). Furthermore, increased LDL cholesterol
      (>150 mg/dL) significantly predicted the occurrence of major adverse cardiac
      events (hazard ratio, 3.09 [95% confidence interval, 1.22-7.87]; P=0.01).
      CONCLUSIONS: In STEMI patients undergoing primary percutaneous coronary
      intervention, baseline LDL cholesterol concentrations were independently
      associated with MVI, revealing a clinically relevant link between LDL metabolism
      and MVI in acute STEMI.

PMID- 29018021
TI  - Short Sleep Duration, Obstructive Sleep Apnea, Shiftwork, and the Risk of Adverse
      Cardiovascular Events in Patients After an Acute Coronary Syndrome.
AB  - BACKGROUND: It is unknown whether short sleep duration, obstructive sleep apnea,
      and overnight shift work are associated with the risk of recurrent cardiovascular
      events in patients after an acute coronary syndrome. METHODS AND RESULTS: SOLID
      TIMI 52 (The Stabilization of PLaques UsIng Darapladib-Thrombolysis in Myocardial
      Infarction 52 Trial) was a multinational, double-blind, placebo-controlled trial
      that enrolled 13 026 patients <=30 days of acute coronary syndrome. At baseline,
      all patients were to complete the Berlin questionnaire to assess risk of
      obstructive sleep apnea and a sleep and shift work survey. Median follow-up was
      2.5 years. The primary outcome was major coronary events (MCE; coronary heart
      disease death, myocardial infarction, or urgent revascularization). Cox models
      were adjusted for clinical predictors. Patients who reported <6 hours sleep per
      night had a 29% higher risk of MCE (adjusted hazard ratio, 1.29; 95% confidence
      interval, 1.12-1.49; P<0.001) compared with those with longer sleep. Patients who
      screened positive for obstructive sleep apnea had a 12% higher risk of MCE (1.12;
      1.00-1.24; P=0.04) than those who did not screen positive. Overnight shift work
      (>=3 night shifts/week for >=1 year) was associated with a 15% higher risk of MCE
      (1.15; 1.03-1.29; P=0.01). A step-wise increase in cardiovascular risk was
      observed for individuals with more than 1 sleep-related risk factor. Individuals
      with all 3 sleep-related risk factors had a 2-fold higher risk of MCE (2.01; 1.49
      2.71; P<0.0001). CONCLUSIONS: Short sleep duration, obstructive sleep apnea, and
      overnight shift work are under-recognized as predictors of adverse outcomes after
      acute coronary syndrome. Increased efforts should be made to identify, treat, and
      educate patients about the importance of sleep for the potential prevention of
      cardiovascular events. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01000727.

PMID- 29018022
TI  - Higher Adiposity Is Associated With Slower Cognitive Decline in Hypertensive
      Patients: Secondary Analysis of the China Stroke Primary Prevention Trial.
AB  - BACKGROUND: Obesity is a risk factor for many diseases. However, the potential
      association between adiposity and cognitive decline in hypertensive patients is
      inconclusive. We performed a secondary data analysis of the CSPPT (China Stroke
      Primary Prevention Trial) to examine whether adiposity is correlated with
      longitudinal cognitive performance in hypertensive adults. METHODS AND RESULTS:
      The analysis included 16 791 patients in the CSPPT who received at least 2
      cognitive assessments by the Mini-Mental State Examination (MMSE) during the
      follow-up (median, 4.5 years; interquartile range, 4.2-4.8 years). Outcomes
      included changes in MMSE scores and cognitive impairment (defined as MMSE score
      less than education-specific cutoff point). A marked reduction in MMSE scores at
      the final (compared with at the 1-year) follow-up was apparent in both men
      (n=4838; mean [SD] score, 0.41 [3.62]) and women (n=7190; mean [SD] score, 1.07
      [4.61]; both P<0.001). Analysis using a mixed-effects model revealed an
      association between higher body mass index with less MMSE decline, even after
      controlling for demographics and comorbidities (men, beta=0.0134 [SE, 0.0036];
      women, beta=0.0133 [SE, 0.0034]; both P<0.001). A total of 1037 men (15.3%) and
      3317 women (33.1%) developed cognitive impairment. In multivariable Cox
      regression analyses, being obese in men (11.3% versus 18.0%; hazard ratio, 0.75;
      95% confidence interval, 0.60-0.94) and women (30.1% versus 36.5%; hazard ratio,
      0.82; 95% confidence interval, 0.74-0.91) was a protective factor against
      cognitive impairment compared with normal body mass index. CONCLUSIONS: Higher
      adiposity is independently associated with slower cognitive decline in Chinese
      hypertensive adults. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00794885 CSPPT.

PMID- 29018024
TI  - Circulatory Dynamics During Pulmonary Vein Isolation Using the Second-Generation
      Cryoballoon.
AB  - BACKGROUND: Circulatory dynamics change during pulmonary vein (PV) isolation
      using cryoballoons. This study sought to investigate the circulatory dynamics
      during cryoballoon-based PV isolation procedures and the contributing factors.
      METHODS AND RESULTS: This study retrospectively included 35 atrial fibrillation
      patients who underwent PV isolation with 28-mm second-generation cryoballoons and
      single 3-minute freeze techniques. Blood pressures were continuously monitored
      via arterial lines. The left ventricular function was evaluated with intracardiac
      echocardiography throughout the procedure in 5 additional patients. Overall, 126
      cryoapplications without interrupting freezing were analyzed. Systolic blood
      pressure (SBP) significantly increased during freezing (138.7+/-28.0 to 148.0+/
      27.2 mm Hg, P<0.001) and sharply dropped (136.3+/-26.0 to 95.0+/-17.9 mm Hg,
      P<0.001) during a mean of 21.0+/-8.0 seconds after releasing the occlusion during
      thawing. In the multivariate analyses, the left PVs (P=0.008) and lower baseline
      SBP (P<0.001) correlated with a larger SBP rise, whereas a higher baseline SBP
      (P<0.001), left PVs (P=0.017), lower balloon nadir temperature (P=0.027), and
      female sex (P=0.045) correlated with larger SBP drops. These changes were
      similarly observed regardless of preprocedural atropine administration and the
      target PV order. PV occlusions without freezing exhibited no SBP change. PV
      antrum freezing without occlusions similarly increased the SBP, but the SBP drop
      was significantly smaller than that with occlusions (P<0.001). The SBP drop time
      course paralleled the left ventricular ejection fraction increase (66.8+/-8.1% to
      79.3+/-6.7%, P<0.001) and systemic vascular resistance index decrease (2667+/
      1024 to 1937+/-513 dynes-sec/cm2 per m2, P=0.002). CONCLUSIONS: With second
      generation cryoballoon-based PV isolation, SBP significantly increased during
      freezing owing to atrial tissue freezing and dropped sharply after releasing the
      occlusion, presumably because of the peripheral vascular resistance decrease
      mainly by circulating chilled blood.

PMID- 29018023
TI  - Mortality and Disability According to Baseline Blood Pressure in Acute Ischemic
      Stroke Patients Treated by Thrombectomy: A Collaborative Pooled Analysis.
AB  - BACKGROUND: High blood pressure (BP) is associated with worse clinical outcomes
      in the setting of acute ischemic stroke, but the optimal blood pressure target is
      still a matter of debate. We aimed to study the association between baseline BP
      and mortality in acute ischemic stroke patients treated by mechanical
      thrombectomy. METHODS AND RESULTS: A total of 1332 acute ischemic stroke patients
      treated by mechanical thrombectomy were enrolled (from January 2012 to June 2016)
      in the ETIS (Endovascular Treatment in Ischemic Stroke) registry. Linear and
      polynomial logistic regression models were used to assess the association between
      BP and mortality and functional outcome at 90 days. Highest mortality was found
      at lower and higher baseline systolic blood pressure (SBP) values following a J-
      or U-shaped relationship, with a nadir at 157 mm Hg (95% confidence interval 143
      170). When SBP values were categorized in 10-mm Hg increments, the odds ratio for
      all-cause mortality was 3.78 (95% confidence interval 1.50-9.55) for SBP<110 mm
      Hg and 1.81 (95% confidence interval 1.01-3.36) for SBP>=180 mm Hg using SBP>=150
      to 160 mm Hg as reference. The rate of favorable outcome was the highest at low
      SBP values and lowest at high SBP values, with a nonlinear relationship; in
      unplanned exploratory analysis, an optimal threshold SBP>=177 mm Hg was found to
      predict unfavorable outcome (adjusted odds ratio 0.47; 95% confidence interval
      0.31-0.70). CONCLUSION: In acute ischemic stroke patients treated by mechanical
      thrombectomy, baseline SBP is associated with all-cause mortality and favorable
      outcome. In contrast to mortality, favorable outcome rate was the highest at low
      SBP values and lowest at high SBP values. Further studies are warranted to
      confirm these findings.

PMID- 29018025
TI  - Peptidyl-Prolyl Isomerase 1 Regulates Ca2+ Handling by Modulating
      Sarco(Endo)Plasmic Reticulum Calcium ATPase and Na2+/Ca2+ Exchanger 1 Protein
      Levels and Function.
AB  - BACKGROUND: Aberrant Ca2+ handling is a prominent feature of heart failure.
      Elucidation of the molecular mechanisms responsible for aberrant Ca2+ handling is
      essential for the development of strategies to blunt pathological changes in
      calcium dynamics. The peptidyl-prolyl cis-trans isomerase peptidyl-prolyl
      isomerase 1 (Pin1) is a critical mediator of myocardial hypertrophy development
      and cardiac progenitor cell cycle. However, the influence of Pin1 on calcium
      cycling regulation has not been explored. On the basis of these findings, the aim
      of this study is to define Pin1 as a novel modulator of Ca2+ handling, with
      implications for improving myocardial contractility and potential for
      ameliorating development of heart failure. METHODS AND RESULTS: Pin1 gene
      deletion or pharmacological inhibition delays cytosolic Ca2+ decay in isolated
      cardiomyocytes. Paradoxically, reduced Pin1 activity correlates with increased
      sarco(endo)plasmic reticulum calcium ATPase (SERCA2a) and Na2+/Ca2+ exchanger 1
      protein levels. However, SERCA2a ATPase activity and calcium reuptake were
      reduced in sarcoplasmic reticulum membranes isolated from Pin1-deficient hearts,
      suggesting that Pin1 influences SERCA2a function. SERCA2a and Na2+/Ca2+ exchanger
      1 associated with Pin1, as revealed by proximity ligation assay in myocardial
      tissue sections, indicating that regulation of Ca2+ handling within
      cardiomyocytes is likely influenced through Pin1 interaction with SERCA2a and
      Na2+/Ca2+ exchanger 1 proteins. CONCLUSIONS: Pin1 serves as a modulator of
      SERCA2a and Na2+/Ca2+ exchanger 1 Ca2+ handling proteins, with loss of function
      resulting in impaired cardiomyocyte relaxation, setting the stage for subsequent
      investigations to assess Pin1 dysregulation and modulation in the progression of
      heart failure.

PMID- 29018028
TI  - Steroid Profiling for Adrenocortical Disorders: A Pathway for Omics-Based
      Diagnostics.

PMID- 29018029
TI  - New Therapies for Treating Hepatitis C Virus: Impact on Laboratory Testing
      Recommendations and Clinical Management.

PMID- 29018026
TI  - Inflammation and Aortic Stiffness: An Individual Participant Data Meta-Analysis
      in Patients With Inflammatory Bowel Disease.
AB  - BACKGROUND: The recent finding that aortic pulse wave velocity (aPWV) is
      increased in patients with inflammatory bowel disease may explain why the
      cardiovascular risk is increased despite the low prevalence of traditional
      cardiovascular risk factors. We aimed to test whether inflammation is associated
      with aortic stiffening in this setting after adjustment for major confounders and
      to perform subgroup analyses. METHODS AND RESULTS: A systematic literature search
      for aPWV in inflammatory bowel disease was performed using PubMed, Scopus, Web of
      Science, and Google Scholar databases (last accessed May 7, 2017). Inclusion
      criterion was peer-reviewed publications on clinical studies reporting original
      data. This study followed the Preferred Reporting Items for Systematic Review and
      Meta-Analyses of individual participant data 2015 guidelines. Data were provided
      for 4 cohorts in 3 countries (151 participants with ulcerative colitis, 159 with
      Crohn's disease, and 227 control patients). Using aPWV, cohort-specific z scores
      were calculated after loge-transform and combined in meta-analysis to form pooled
      effects using a random-effects model. Compared with controls, aPWV was increased
      in patients with Crohn's disease (mean difference 0.78 z score; 95% confidence
      interval, 0.56-1.00 z score [P<0.001]) and ulcerative colitis (mean difference
      0.75 z score; 95% confidence interval, 0.52-0.97 z score [P<0.001]). In an
      outlier-robust multivariate linear regression model adjusted for prespecified
      confounders, aPWV was associated with disease duration (years, beta=0.05 z score;
      95% confidence interval, 0.02-0.08 z score [P<0.001]) and white blood cell count
      (billion cells/L, beta=0.07 z score; 95% confidence interval, 0.02-0.11 z score
      [P=0.002]) but not with markers of acute inflammation (C-reactive protein and
      erythrocyte sedimentation rate), cardiovascular risk factors, and therapy.
      CONCLUSIONS: The increased aPWV reported in patients with inflammatory bowel
      disease is associated with inflammation. CLINICAL TRIAL REGISTRATION: URL:
      http://www.crd.york.ac.uk. Unique identifier: PROSPERO 2016: CRD42016053070.

PMID- 29018030
TI  - General practice threatens to withhold repeat prescriptions until patients have
      flu vaccine.

PMID- 29018031
TI  - #ILookLikeASurgeon: embracing diversity to improve patient outcomes.

PMID- 29018027
TI  - Abdominal Aortic Calcifications Influences the Systemic and Renal Hemodynamic
      Response to Renal Denervation in the DENERHTN (Renal Denervation for
      Hypertension) Trial.
AB  - BACKGROUND: The DENERHTN (Renal Denervation for Hypertension) trial confirmed the
      efficacy of renal denervation (RDN) in lowering daytime ambulatory systolic blood
      pressure when added to standardized stepped-care antihypertensive treatment
      (SSAHT) for resistant hypertension at 6 months. METHODS AND RESULTS: This post
      hoc exploratory analysis assessed the impact of abdominal aortic calcifications
      (AAC) on the hemodynamic and renal response to RDN at 6 months. In total, 106
      patients with resistant hypertension were randomly assigned to RDN plus SSAHT or
      to the same SSAHT alone (control group). Total AAC volume was measured, with
      semiautomatic software and blind to randomization, from the aortic hiatus to the
      iliac bifurcation using the prerandomization noncontrast abdominal computed
      tomography scans of 90 patients. Measurements were expressed as tertiles. The
      baseline-adjusted difference in the change in daytime ambulatory systolic blood
      pressure from baseline to 6 months between the RDN and control groups was -10.1
      mm Hg (P=0.0462) in the lowest tertile and -2.5 mm Hg (P=0.4987) in the 2 highest
      tertiles of AAC volume. Estimated glomerular filtration rate remained stable at 6
      months for the patients in the lowest tertile of AAC volume who underwent RDN
      (+2.5 mL/min per 1.73 m2) but decreased in the control group (-8.0 mL/min per
      1.73 m2, P=0.0148). In the 2 highest tertiles of AAC volume, estimated glomerular
      filtration rate decreased similarly in the RDN and control groups (P=0.2640).
      CONCLUSIONS: RDN plus SSAHT resulted in a larger decrease in daytime ambulatory
      systolic blood pressure than SSAHT alone in patients with a lower AAC burden than
      in those with a higher AAC burden. This larger decrease in daytime ambulatory
      systolic blood pressure was not associated with a decrease in estimated
      glomerular filtration rate. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01570777.

PMID- 29018032
TI  - N-Acetyltransferase 2 Genotype-Dependent N-Acetylation of Hydralazine in Human
      Hepatocytes.
AB  - Hydralazine is used in the treatment of essential hypertension and is under
      investigation for epigenetic therapy in the treatment of neoplastic and renal
      diseases. N-acetyltransferase (NAT) 2 exhibits a common genetic polymorphism in
      human populations. After recombinant expression in yeast, human NAT2 exhibited an
      apparent Lineweaver-Burk constant (K-m) value (20.1 +/- 8.8 MUM) for hydralazine
      over 20-fold lower than the apparent K-m value (456 +/- 57 MUM) for recombinant
      human NAT1 (P = 0.0016). The apparent Vmax value for recombinant human NAT1 (72.2
      +/- 17.9 nmol acetylated/min/mg protein) was significantly (P = 0.0245) lower
      than recombinant human NAT2 (153 +/- 15 nmol acetylated/min/mg protein),
      reflecting 50-fold higher clearance for recombinant human NAT2. Hydralazine NAT
      activities exhibited a robust acetylator gene dose response in cryopreserved
      human hepatocytes both in vitro and in situ. Hydralazine NAT activities in vitro
      differed significantly with respect to NAT2 genotype at 1000 (P = 0.0319), 100 (P
      = 0.002), and 10 MUM hydralazine (P = 0.0029). Hydralazine NAT activities
      differed significantly (P < 0.001) among slow acetylator hepatocytes,
      (NAT2*5B/*5B > NAT2*5B/*6A > NAT2*6A/*6A). The in situ hydralazine N-acetylation
      rates differed significantly with respect to NAT2 genotype after incubation with
      10 (P = 0.002) or 100 uM (P = 0.0015) hydralazine and were higher after
      incubation with 100 MUM (10-fold) than with 10 MUM (4.5-fold) hydralazine. Our
      results clearly document NAT2 genotype-dependent N-acetylation of hydralazine in
      human hepatocytes, suggesting that hydralazine efficacy and safety could be
      improved by NAT2 genotype-dependent dosing strategies.

PMID- 29018033
TI  - Expression and Functional Characterization of Breast Cancer-Associated Cytochrome
      P450 4Z1 in Saccharomyces cerevisiae.
AB  - CYP4Z1 is an "orphan" cytochrome P450 (P450) enzyme that has provoked interest
      because of its hypothesized role in breast cancer through formation of the
      signaling molecule 20-hydroxyeicosatetraenoic acid (20-HETE). We expressed human
      CYP4Z1 in Saccharomyces cerevisiae and evaluated its catalytic capabilities
      toward arachidonic and lauric acids (AA and LA). Specific and sensitive mass
      spectrometry assays enabled discrimination of the regioselectivity of
      hydroxylation of these two fatty acids. CYP4Z1 generated 7-, 8-, 9-, 10-, and 11
      hydroxy LA, whereas the 12-hydroxy metabolite was not detected. HET0016, the
      prototypic CYP4 inhibitor, only weakly inhibited laurate metabolite formation
      (IC50 ~15 MUM). CYP4Z1 preferentially oxidized AA to the 14(S),15(R)-epoxide with
      high regioselectivity and stereoselectivity, a reaction that was also insensitive
      to HET0016, but neither 20-HETE nor 20-carboxy-AA were detectable metabolites.
      Docking of LA and AA into a CYP4Z1 homology model was consistent with this
      preference for internal fatty acid oxidation. Thus, human CYP4Z1 has an inhibitor
      profile and product regioselectivity distinct from most other CYP4 enzymes,
      consistent with CYP4Z1's lack of a covalently linked heme. These data suggest
      that, if CYP4Z1 modulates breast cancer progression, it does so by a mechanism
      other than direct production of 20-HETE.

PMID- 29018036
TI  - CCND2 Overexpression Enhances the Regenerative Potency of Human Induced
      Pluripotent Stem Cell-Derived Cardiomyocytes: Remuscularization of Injured
      Ventricle.
AB  - RATIONALE: The effectiveness of transplanted, human induced pluripotent stem cell
      derived cardiomyocytes (hiPSC-CMs) for treatment of ischemic myocardial injury is
      limited by the exceptionally low engraftment rate. OBJECTIVE: To determine
      whether overexpression of the cell cycle activator CCND2 (cyclin D2) in hiPSC-CMs
      can increase the graft size and improve myocardial recovery in a mouse model of
      myocardial infarction by increasing the proliferation of grafted cells. METHODS
      AND RESULTS: Human CCND2 was delivered to hiPSCs via lentiviral-mediated gene
      transfection. In cultured cells, markers for cell cycle activation and
      proliferation were ~3- to 7-folds higher in CCND2-overexpressing hiPSC-CMs (hiPSC
      CCND2OECMs) than in hiPSC-CMs with normal levels of CCND2 (hiPSC-CCND2WTCMs;
      P<0.01). The pluripotent genes (Oct 4, Sox2, and Nanog) decrease to minimal
      levels and undetectable levels at day 1 and 10 after differentiating to CMs. In
      the mouse myocardial infarction model, cardiac function, infarct size, and the
      number of engrafted cells were similar at week 1 after treatment with hiPSC
      CCND2OECMs or hiPSC-CCND2WTCMs but was about tripled in hiPSC-CCND2OECM-treated
      than in hiPSC-CCND2WTCM-treated animals at week 4 (P<0.01). The cardiac function
      and infarct size were significantly better in both cell treatment groups' hearts
      than in control hearts, which was most prominent in hiPSC-CCND2OECM-treated
      animals (P<0.05, each). No tumor formation was observed in any hearts.
      CONCLUSIONS: CCND2 overexpression activates cell cycle progression in hiPSC-CMs
      that results in a significant enhanced potency for myocardial repair as evidenced
      by remuscularization of injured myocardium. This left ventricular muscle
      regeneration and increased angiogenesis in border zone are accompanied by a
      significant improvement of left ventricular chamber function.

PMID- 29018035
TI  - Trials and Tribulations of CETP Inhibitors.
AB  - The development of CETP (cholesteryl ester transfer protein) inhibitors has had a
      long and difficult course with 3 compounds failing in phase III clinical trials.
      Finally, the REVEAL (Randomized Evaluation of the Effects of Anacetrapib through
      Lipid modification) trial has shown that the CETP inhibitor anacetrapib decreased
      coronary heart disease when added to statin therapy. Although the result is
      different to earlier studies, this is likely related to the size and duration of
      the trial. The benefit of anacetrapib seems to be largely explained by lowering
      of non-HDL-C (high-density lipoprotein cholesterol), rather than increases in HDL
      C. Although the magnitude of benefit for coronary heart disease appeared to be
      moderate, in part this may have reflected aspects of the trial design.
      Anacetrapib treatment was associated with a small increase in blood pressure, but
      was devoid of major side effects and was also associated with a small reduction
      in diabetes mellitus. Treatment with CETP inhibitors, either alone or in
      combination with statins, could provide another option for patients with coronary
      disease who require further reduction in LDL (low-density lipoprotein) and non
      HDL-C.

PMID- 29018034
TI  - Distinct Cellular Basis for Early Cardiac Arrhythmias, the Cardinal Manifestation
      of Arrhythmogenic Cardiomyopathy, and the Skin Phenotype of Cardiocutaneous
      Syndromes.
AB  - RATIONALE: Arrhythmogenic cardiomyopathy is caused primarily by mutations in
      genes encoding desmosome proteins. Ventricular arrhythmias are the cardinal and
      typically early manifestations, whereas myocardial fibroadiposis is the
      pathological hallmark. Homozygous DSP (desmoplakin) and JUP (junction protein
      plakoglobin) mutations are responsible for a subset of patients with
      arrhythmogenic cardiomyopathy who exhibit cardiac arrhythmias and dysfunction,
      palmoplanter keratosis, and hair abnormalities (cardiocutaneous syndromes).
      OBJECTIVE: To determine phenotypic consequences of deletion of Dsp in a subset of
      cells common to the heart and skin. METHODS AND RESULTS: Expression of CSPG4
      (chondroitin sulfate proteoglycan 4) was detected in epidermal keratinocytes and
      the cardiac conduction system. CSPG4pos cells constituted ~5.6+/-3.3% of the
      nonmyocyte cells in the mouse heart. Inducible postnatal deletion of Dsp under
      the transcriptional control of the Cspg4 locus led to ventricular arrhythmias,
      atrial fibrillation, atrioventricular conduction defects, and death by 4 months
      of age. Cardiac arrhythmias occurred early and in the absence of cardiac
      dysfunction and excess cardiac fibroadipocytes, as in human arrhythmogenic
      cardiomyopathy. The mice exhibited palmoplantar keratosis and progressive
      alopecia, leading to alopecia totalis, associated with accelerated proliferation
      and impaired terminal differentiation of keratinocytes. The phenotype is similar
      to human cardiocutaneous syndromes caused by homozygous mutations in DSP.
      CONCLUSIONS: Deletion of Dsp under the transcriptional regulation of the CSPG4
      locus led to lethal cardiac arrhythmias in the absence of cardiac dysfunction or
      fibroadiposis, palmoplantar keratosis, and alopecia, resembling the human
      cardiocutaneous syndromes. The findings offer a cellular basis for early cardiac
      arrhythmias in patients with arrhythmogenic cardiomyopathy and cardiocutaneous
      syndromes.

PMID- 29018039
TI  - The ocean lifeguard drowning prevention paradigm: how and where do lifeguards
      intervene in the drowning process?
AB  - Drowning is a global health problem that can be addressed with multiple
      strategies including utilisation of lifeguards in recreational swim areas.
      However, few studies have described lifeguard prevention activities. We conducted
      a retrospective analysis using lifeguard activity data collected in real time
      with a Computer-Aided-Dispatch (CAD) system to characterise the nature of
      lifeguard primary and secondary drowning prevention at a popular ocean beach in
      California. Preventative actions constituted the majority (232 065/423 071;
      54.8%) of lifeguard activities, while rescues represented 1.9%. Most preventative
      actions and rescues occurred during summer months, weekends and afternoons.
      Statistically significant geographical clusters of preventative actions were
      identified all over the beach, while rescue clusters were primarily restricted to
      two sites. Using the most reliable and valid collection system to date, these
      data show spatial and temporal patterns for ocean lifeguard provision of primary
      prevention as well as secondary drowning prevention (rescue).

PMID- 29018037
TI  - Chromatin remodeler CHD1 promotes XPC-to-TFIIH handover of nucleosomal UV lesions
      in nucleotide excision repair.
AB  - Ultraviolet (UV) light induces mutagenic cyclobutane pyrimidine dimers (CPDs) in
      nucleosomal DNA that is tightly wrapped around histone octamers. How global
      genome nucleotide excision repair (GG-NER) processes CPDs despite that this
      chromatin arrangement is poorly understood. An increased chromatin association of
      CHD1 (chromodomain helicase DNA-binding 1) upon UV irradiation indicated possible
      roles of this chromatin remodeler in the UV damage response. Immunoprecipitation
      of chromatin fragments revealed that CHD1 co-localizes in part with GG-NER
      factors. Chromatin fractionation showed that the UV-dependent recruitment of CHD1
      occurs to UV lesions in histone-assembled nucleosomal DNA and that this CHD1
      relocation requires the lesion sensor XPC (xeroderma pigmentosum group C). In
      situ immunofluorescence analyses further demonstrate that CHD1 facilitates
      substrate handover from XPC to the downstream TFIIH (transcription factor IIH).
      Consequently, CHD1 depletion slows down CPD excision and sensitizes cells to UV
      induced cytotoxicity. The finding of a CHD1-driven lesion handover between
      sequentially acting GG-NER factors on nucleosomal histone octamers suggests that
      chromatin provides a recognition scaffold enabling the detection of a subset of
      CPDs.

PMID- 29018038
TI  - Increased localization of APP-C99 in mitochondria-associated ER membranes causes
      mitochondrial dysfunction in Alzheimer disease.
AB  - In the amyloidogenic pathway associated with Alzheimer disease (AD), the amyloid
      precursor protein (APP) is cleaved by beta-secretase to generate a 99-aa C
      terminal fragment (C99) that is then cleaved by gamma-secretase to generate the
      beta-amyloid (Abeta) found in senile plaques. In previous reports, we and others
      have shown that gamma-secretase activity is enriched in mitochondria-associated
      endoplasmic reticulum (ER) membranes (MAM) and that ER-mitochondrial connectivity
      and MAM function are upregulated in AD We now show that C99, in addition to its
      localization in endosomes, can also be found in MAM, where it is normally
      processed rapidly by gamma-secretase. In cell models of AD, however, the
      concentration of unprocessed C99 increases in MAM regions, resulting in elevated
      sphingolipid turnover and an altered lipid composition of both MAM and
      mitochondrial membranes. In turn, this change in mitochondrial membrane
      composition interferes with the proper assembly and activity of mitochondrial
      respiratory supercomplexes, thereby likely contributing to the bioenergetic
      defects characteristic of AD.

PMID- 29018040
TI  - Effectiveness of child restraints and booster legislation in Israel.
AB  - INTRODUCTION: 96 countries in the world have enacted child restraints and booster
      legislation (CRBL). Yet, findings regarding the effectiveness of CRBLs are mixed.
      The current study is the first to examine the association between Israel's CRBL,
      implemented in November 2004, and the traffic injury and fatality rates among
      children aged 0-9 years. We extend on previous studies by accounting for risk
      exposure and by comparing populations of children affected by the legislation to
      those who were not. METHODS: We used an interrupted time series design of
      kilometre driven-based traffic injury rates for children aged 0-4 years and
      children aged 5-9 years using childred aged 10-14 years as a comparison group. We
      estimated the effects of Israel's CRBL using monthly injury and fatality count
      data from the Israeli Central Bureau of Statistics. The sample includes all child
      vehicle occupants injured and killed in crashes in Israel between January 2003
      and December 2011. RESULTS: Children aged 0-4 years experienced a 5.17% yearly
      reduction in traffic injury rate (incidence rate ratio (IRR): 0.94(95% CI 0.92 to
      0.96); p=0.000), and the injury rate for children aged 5-9 years was associated
      with a 4.10% yearly reduction (IRR: 0.95(95% CI 0.93 to 0.98); p=0.001). The
      comprehensive CRBL implemented in Israel was associated with a 6.3% (95% CI -7.2%
      to5.5%; p=0.001) reduction in traffic injuries and fatalities for children aged 0
      9 years. CONCLUSION: This is the first study comparing traffic injury rates per
      kilometre driven for motor vehicle-occupant children before and after the
      implementation of the CRBL in Israel.

PMID- 29018041
TI  - Spontaneous Breathing Trials and Conservative Sedation Practices Reduce
      Mechanical Ventilation Duration in Subjects With ARDS.
AB  - BACKGROUND: Spontaneous breathing trials (SBTs) and daily sedation interruptions
      (DSIs) reduce both the duration of mechanical ventilation and ICU length of stay
      (LOS). The impact of these practices in patients with ARDS has not previously
      been reported. We examined whether implementation of SBT/DSI protocols reduce
      duration of mechanical ventilation and ICU LOS in a retrospective group of
      subjects with ARDS at a large, urban, level-1 trauma center. METHODS: All ARDS
      survivors from 2002 to 2016 (N = 1,053) were partitioned into 2 groups: 397 in
      the pre-SBT/DSI group (June 2002-December 2007) and 656 in the post-SBT/DSI group
      (January 2009-April 2016). Patients from 2008, during the protocol implementation
      period, were excluded. An additional SBT protocol database (2008-2010) was used
      to assess the efficacy of SBT in transitioning subjects with ARDS to unassisted
      breathing. Comparisons were assessed by either unpaired t tests or Mann-Whitney
      tests. Multiple comparisons were made using either one-way analysis of variance
      or Kruskal-Wallis and Dunn's tests. Linear regression modeling was used to
      determine variables independently associated with mechanical ventilation duration
      and ICU LOS; differences were considered statistically significant when P < .05.
      RESULTS: Compared to the pre-protocol group, subjects with ARDS managed with
      SBT/DSI protocols experienced pronounced reductions both in median (IQR)
      mechanical ventilation duration (14 [6-29] vs 9 [4-17] d, respectively, P < .001)
      and median ICU LOS (18 [8-33] vs 13 [7-22] d, respectively P < .001). In the
      final model, only treatment in the SBT/DSI period and higher baseline respiratory
      system compliance were independently associated with reduced mechanical
      ventilation duration and ICU LOS. Among subjects with ARDS in the SBT performance
      database, most achieved unassisted breathing with a median of 2 SBTs. CONCLUSION:
      Evidenced-based protocols governing weaning and sedation practices were
      associated with both reduced mechanical ventilation duration and ICU LOS in
      subjects with ARDS. However, higher respiratory system compliance in the SBT/DSI
      cohort also contributed to these improved outcomes.

PMID- 29018043
TI  - Educational Added Value Unit: Development and Testing of a Measure for
      Educational Activities.
AB  - OBJECTIVES: University-based hospitalists educate health care professionals as an
      expectation, often lacking time and support for these activities. The purpose of
      this study was to (1) develop a tracking tool to record educational activities,
      (2) demonstrate its applicability and ease of completion for faculty members in
      different divisions, and (3) compare educational efforts of individuals from
      different professional pathways and divisions by using the educational added
      value unit (EAVU). METHODS: Educational activities were selected and ranked
      according to preparation effort, presentation time, and impact to calculate the
      EAVU. Faculty participants from 5 divisions at 1 institution (hospital medicine,
      general and community pediatrics, emergency medicine, behavior medicine and
      clinical psychology, and biostatistics and epidemiology) completed the
      retrospective, self-report tracking tool. RESULTS: A total of 62% (74 of 119) of
      invited faculty members participated. All faculty earned some EAVUs; however,
      there was a wide distribution range. The median EAVU varied by division (hospital
      medicine [21.7], general and community pediatrics [20.6], emergency medicine
      [26.1], behavior medicine and clinical psychology [18.3], and biostatistics and
      epidemiology [8.2]). Faculty on the educator pathway had a higher median EAVU
      compared with clinical or research pathways. CONCLUSIONS: The EAVU tracking tool
      holds promise as a mechanism to track educational activities of different faculty
      pathways. EAVU collection could be of particular benefit to hospitalists, who
      often perform unsupported teaching activities. Additional studies are needed to
      determine how to apply a similar process in different institutions and to
      determine how EAVUs could be used for additional support for teaching, curriculum
      development, and educational scholarship.

PMID- 29018042
TI  - GWAS on prolonged gestation (post-term birth): analysis of successive Finnish
      birth cohorts.
AB  - BACKGROUND: Gestation is a crucial timepoint in human development. Deviation from
      a term gestational age correlates with both acute and long-term adverse health
      effects for the child. Both being born preterm and post-term, that is, having
      short and long gestational ages, are heritable and influenced by the prenatal and
      perinatal environment. Despite the obvious heritable component, specific genetic
      influences underlying differences in gestational age are poorly understood.
      METHODS: We investigated the genetic architecture of gestational age in 9141
      individuals, including 1167 born post-term, across two Northern Finland cohorts
      born in 1966 or 1986. RESULTS: Here we identify one globally significant intronic
      genetic variant within the ADAMTS13 gene that is associated with prolonged
      gestation (p=4.85*10-8). Additional variants that reached suggestive levels of
      significance were identified within introns at the ARGHAP42 and TKT genes, and in
      the upstream (5') intergenic regions of the B3GALT5 and SSBP2 genes. The variants
      near the ADAMTS13, B3GALT5, SSBP2 and TKT loci are linked to alterations in gene
      expression levels (cis-eQTLs). Luciferase assays confirmed the allele specific
      enhancer activity for the BGALT5 and TKT loci. CONCLUSIONS: Our findings provide
      the first evidence of a specific genetic influence associated with prolonged
      gestation. This study forms a foundation for a better understanding of the
      genetic and long-term health risks faced by induced and post-term individuals.
      The long-term risks for induced individuals who have a previously overlooked post
      term potential may be a major issue for current health providers.

PMID- 29018044
TI  - Rnf43.
AB  - RNF43 (E3 ubiquitin-protein ligase RNF43 or RING-type E3 ubiquitin transferase
      RNF43) functions as a tumor suppressor, by exerting a predominant negative
      feedback mechanism in the Wnt/beta-catenin signaling pathway. RNF43 inhibits
      Wnt/beta-catenin signaling by ubiquitinating Frizzled receptor and targeting it
      to the lysosomal pathway for degradation. Loss of function of RNF43 results in
      decrease/lack of degradation of Frizzled with enhancement of Wnt/beta-catenin
      signaling pathway. Mutations of RNF43 have been reported in different cancers. We
      describe the structure of RNF43, its function and most frequent mutations in
      different cancers.

PMID- 29018047
TI  - Type 1 Diabetes and Celiac Disease: Causal Association or True, True, Unrelated?

PMID- 29018045
TI  - PTEN drives Th17 cell differentiation by preventing IL-2 production.
AB  - T helper 17 (Th17) cells are a CD4+ T cell subset that produces IL-17A to mediate
      inflammation and autoimmunity. IL-2 inhibits Th17 cell differentiation. However,
      the mechanism by which IL-2 is suppressed during Th17 cell differentiation
      remains unclear. Here, we show that phosphatase and tensin homologue (PTEN) is a
      key factor that regulates Th17 cell differentiation by suppressing IL-2
      production. Th17-specific Pten deletion (Ptenfl/flIl17acre ) impairs Th17 cell
      differentiation in vitro and ameliorated symptoms of experimental autoimmune
      encephalomyelitis (EAE), a model of Th17-mediated autoimmune disease.
      Mechanistically, Pten deficiency up-regulates IL-2 and phosphorylation of STAT5,
      but reduces STAT3 phosphorylation, thereby inhibiting Th17 cell differentiation.
      PTEN inhibitors block Th17 cell differentiation in vitro and in the EAE model.
      Thus, PTEN plays a key role in Th17 cell differentiation by blocking IL-2
      expression.

PMID- 29018048
TI  - How to "ENGAGE" Multilevel Learner Groups in the Clinical Setting.

PMID- 29018049
TI  - Statins in venous thrombosis: more evidence, more basic science findings.

PMID- 29018050
TI  - Jumping the Barrier: Modeling Drug Penetration across the Blood-Brain Barrier.
AB  - Determining the penetration of drugs across the blood-brain barrier is a
      significant challenge in central nervous system drug development. The use of a
      mechanistic physiologically based pharmacokinetic model can predict drug
      exposures in the brain without needing in situ drug measurements. Clin Cancer
      Res; 23(24); 7437-9. (c)2017 AACRSee related article by Li et al., p. 7454.

PMID- 29018051
TI  - Phase III HEAT Study Adding Lyso-Thermosensitive Liposomal Doxorubicin to
      Radiofrequency Ablation in Patients with Unresectable Hepatocellular Carcinoma
      Lesions.
AB  - Purpose: Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of
      doxorubicin contained within a heat-sensitive liposome. When heated to >=40
      degrees C, LTLD locally releases a high concentration of doxorubicin. We aimed to
      determine whether adding LTLD improves the efficacy of radiofrequency ablation
      (RFA) for hepatocellular carcinoma (HCC) lesions with a maximum diameter (dmax)
      of 3 to 7 cm.Experimental Design: The HEAT Study was a randomized, double-blind,
      dummy-controlled trial of RFA +/- LTLD. The 701 enrolled patients had to have <=4
      unresectable HCC lesions, at least one of which had a dmax of 3 to 7 cm. The
      primary endpoint was progression-free survival (PFS) and a key secondary endpoint
      was overall survival (OS). Post hoc subset analyses investigated whether RFA
      duration was associated with efficacy.Results: The primary endpoint was not met;
      in intention-to-treat analysis, the PFS HR of RFA + LTLD versus RFA alone was
      0.96 [95% confidence interval (CI), 0.79-1.18; P = 0.71], and the OS HR ratio was
      0.95 (95% CI, 0.76-1.20; P = 0.67). Among 285 patients with a solitary HCC lesion
      who received >=45 minutes RFA dwell time, the OS HR was 0.63 (95% CI, 0.41-0.96;
      P < 0.05) in favor of combination therapy. RFA + LTLD had reversible
      myelosuppression similar to free doxorubicin.Conclusions: Adding LTLD to RFA was
      safe but did not increase PFS or OS in the overall study population. However,
      consistent with LTLD's heat-based mechanism of action, subgroup analysis
      suggested that RFA + LTLD efficacy is improved when RFA dwell time for a solitary
      lesion >=45 minutes. Clin Cancer Res; 24(1); 73-83. (c)2017 AACR.

PMID- 29018052
TI  - Intratumoral HPV16-Specific T Cells Constitute a Type I-Oriented Tumor
      Microenvironment to Improve Survival in HPV16-Driven Oropharyngeal Cancer.
AB  - Purpose: Human papillomavirus (HPV)-associated oropharyngeal squamous cell cancer
      (OPSCC) has a much better prognosis than HPV-negative OPSCC, and this is linked
      to dense tumor immune infiltration. As the viral antigens may trigger potent
      immunity, we studied the relationship between the presence of intratumoral HPV
      specific T-cell responses, the immune contexture in the tumor microenvironment,
      and clinical outcome.Experimental Design: To this purpose, an in-depth analysis
      of tumor-infiltrating immune cells in a prospective cohort of 97 patients with
      HPV16-positive and HPV16-negative OPSCC was performed using functional T-cell
      assays, mass cytometry (CyTOF), flow cytometry, and fluorescent immunostaining of
      tumor tissues. Key findings were validated in a cohort of 75 patients with HPV16
      positive OPSCC present in the publicly available The Cancer Genome Atlas
      database.Results: In 64% of the HPV16-positive tumors, type I HPV16-specific T
      cells were present. Their presence was not only strongly related to a better
      overall survival, a smaller tumor size, and less lymph node metastases but also
      to a type I-oriented tumor microenvironment, including high numbers of activated
      CD161+ T cells, CD103+ tissue-resident T cells, dendritic cells (DC), and DC-like
      macrophages.Conclusions: The viral antigens trigger a tumor-specific T-cell
      response that shapes a favorable immune contexture for the response to standard
      therapy. Hence, reinforcement of HPV16-specific T-cell reactivity is expected to
      boost this process. Clin Cancer Res; 24(3); 634-47. (c)2017 AACRSee related
      commentary by Laban and Hoffmann, p. 505.

PMID- 29018046
TI  - Co-occurrence of Type 1 Diabetes and Celiac Disease Autoimmunity.
AB  - BACKGROUND AND OBJECTIVES: Few birth cohorts have prospectively followed
      development of type 1 diabetes (T1D) and celiac disease (CD) autoimmunities to
      determine timing, extent of co-occurrence, and associated genetic and demographic
      factors. METHODS: In this prospective birth cohort study, 8676 children at high
      genetic risk of both diseases were enrolled and 5891 analyzed in median follow-up
      of 66 months. Along with demographic factors and HLA-DR-DQ, genotypes for HLA
      DPB1 and 5 non-HLA loci conferring risk of both T1D and CD were analyzed.
      RESULTS: Development of persistent islet autoantibodies (IAs) and tissue
      transglutaminase autoantibodies (tTGAs), as well as each clinical disease, was
      evaluated quarterly from 3 to 48 months of age and semiannually thereafter. IAs
      alone appeared in 367, tTGAs alone in 808, and both in 90 children. Co-occurrence
      significantly exceeded the expected rate. IAs usually, but not always, appeared
      earlier than tTGAs. IAs preceding tTGAs was associated with increasing risk of
      tTGAs (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.15-1.91). After
      adjusting for country, sex, family history, and all other genetic loci,
      significantly greater co-occurrence was observed in children with a T1D family
      history (HR: 2.80), HLA-DR3/4 (HR: 1.94) and single-nucleotide polymorphism
      rs3184504 at SH2B3 (HR: 1.53). However, observed co-occurrence was not fully
      accounted for by all analyzed factors. CONCLUSIONS: In early childhood, T1D
      autoimmunity usually precedes CD autoimmunity. Preceding IAs significantly
      increases the risk of subsequent tTGAs. Co-occurrence is greater than explained
      by demographic factors and extensive genetic risk loci, indicating that shared
      environmental or pathophysiological mechanisms may contribute to the increased
      risk.

PMID- 29018053
TI  - Fluorescein-Guided Surgery for Resection of High-Grade Gliomas: A Multicentric
      Prospective Phase II Study (FLUOGLIO).
AB  - Purpose: Sodium fluorescein is a dye that, intravenously injected, selectively
      accumulates in high-grade glioma (HGG) tissue through a damaged blood-brain
      barrier. In this article, the final results of a multicentric prospective phase
      II trial (FLUOGLIO) on fluorescein-guided HGG resection through a dedicated
      filter on the surgical microscope were reported.Methods: Patients with suspected
      HGGs considered suitable for removal were eligible to participate in this trial.
      Fluorescein was intravenously injected at a dose of 5 to 10 mg/kg. The primary
      endpoint was the percentage of patients with histologically confirmed HGGs,
      without contrast-enhancing tumor at the immediate postoperative MRI. Secondary
      endpoints were PFS, residual tumor on postoperative MRI, overall survival,
      neurologic deficits, and fluorescein-related toxicity. The sensitivity and
      specificity of fluorescein in identifying tumor tissue were estimated by
      fluorescent and nonfluorescent biopsies at the tumor margin. The study was
      registered on the European Regulatory Authorities website (EudraCT 2011-002527
      18).Results: Fifty-seven patients aged 45 to 75 years were screened for
      participation, and 46 were considered for primary and secondary endpoints. Mean
      preoperative tumor volume was 28.75 cm3 (range, 1.3-87.8 cm3). Thirty-eight
      patients (82.6%) underwent a complete tumor removal. Median follow-up was 11
      months. PFS-6 and PFS-12 were 56.6% and 15.2%. Median survival was 12 months. No
      adverse reaction related to SF administration was recorded. The sensitivity and
      specificity of fluorescein in identifying tumor tissue were respectively 80.8%
      and 79.1%.Conclusions: Fluorescein-guided technique with a dedicated filter on
      the surgical microscope is safe and enables a high percentage of contrast
      enhancing tumor in patients with HGGs. Clin Cancer Res; 24(1); 52-61. (c)2017
      AACR.

PMID- 29018054
TI  - The induction of myeloma cell death and DNA damage by tetrac, a thyroid hormone
      derivative.
AB  - Multiple myeloma (MM) is a plasma cell malignancy in which involvement of the
      thyroid hormone-integrin alphavbeta3 pathway was shown, and pharmacologic
      inhibition of this pathway is a rational approach to disease management. A
      thyroid hormone derivative, tetraiodothyroacetic acid (tetrac), which inhibits l
      thyroxine (T4) and 3,5,3'-triiodo-l-thyronine (T3) binding to alphavbeta3
      integrin, was studied in five MM cell lines and primary bone marrow (BM) MM
      cells. Tetrac inhibited MM cell proliferation (absolute cell number/viability)
      and induced caspase-dependent apoptosis (annexin-V/PI and cell cycle). Activation
      of caspase-9 and caspase-3 was further demonstrated. Moreover, DNA damage
      markers, ataxia-telangiectasia-mutated (ATM) kinase, poly ADP-ribose polymerase
      (PARP-1) and histone gammaH2AX were induced by tetrac. The various tetrac
      initiated effects were attenuated by Arg-Gly-Asp (RGD) peptide, suggesting
      integrin involvement. Primary BM mononuclear cells were harvested from MM
      patients (n = 39) at various disease stages. Tetrac-induced apoptosis (12/17
      samples) and sensitized the cytotoxic action of bortezomib (6/9 samples). Lastly,
      expression of plasma membrane integrin alphavbeta3 was shown not only in the
      malignant plasma clone, but also in other cell populations within the BM samples
      (n = 25). Tetrac is anti-proliferative and pro-apoptotic in MM and cells may
      offer a therapeutic approach for this disease.

PMID- 29018055
TI  - Dose-response effects of exercise on insulin among colon cancer survivors.
AB  - Physical activity is associated with a lower risk of disease recurrence among
      colon cancer survivors. The pathways through which physical activity may alter
      disease outcomes are unknown, but may include changes in metabolic growth
      factors, such as insulin. Between January 2015 and August 2015, 39 stage I-III
      colon cancer survivors were randomized to one of the three groups: usual care
      control, 150 min/week of aerobic exercise (low-dose) and 300 min/week of aerobic
      exercise (high-dose) for six months. The pre-specified key metabolic growth
      factor outcome was fasting insulin. Insulin resistance was quantified using the
      homeostatic model assessment. Mean age was 56.5 +/- 10.0 years, 51% had stage III
      disease, 72% were treated with chemotherapy and the mean time since finishing
      treatment was 10.9 +/- 6.1 months. Over six months, the low-dose group completed
      141.5 +/- 9.9 min/week of aerobic exercise, and the high-dose group completed
      247.2 +/- 10.7 min/week of aerobic exercise. Fasting insulin concentrations
      decreased 7.4 +/- 9.4 pmol/L in the control group, 28.0 +/- 8.3 pmol/L in the low
      dose group and 20.7 +/- 9.3 pmol/L in the high-dose group (nonlinear Ptrend =
      0.042). Insulin resistance decreased 0.11 +/- 0.20 in the control group, 0.63 +/-
      0.17 in the low-dose group and 0.43 +/- 0.19 in the high-dose group (nonlinear
      Ptrend = 0.012). Aerobic exercise reduces insulin concentrations and insulin
      resistance among patients with stage I-III colon cancer. Prescribing 150 min/week
      of aerobic exercise may be sufficient for reducing insulin concentrations and
      insulin resistance, which may partially mediate the relationship between physical
      activity and colon cancer prognosis.

PMID- 29018058
TI  - Impact of an inpatient electronic prescribing system on prescribing error
      causation: a qualitative evaluation in an English hospital.
AB  - BACKGROUND: Few studies have applied a systems approach to understanding the
      causes of specific prescribing errors in the context of hospital electronic
      prescribing (EP). A comprehensive understanding of underlying causes is essential
      for developing effective interventions to improve prescribing safety. Our
      objectives were to explore prescribers' perspectives of the causes of errors
      occurring with EP and to make recommendations to maximise benefits and minimise
      risks. METHODS: We studied a large hospital using inpatient EP. From April to
      June 2016, semistructured interviews were conducted with purposively sampled
      prescribers involved with a prescribing error. Interviews explored prescribers'
      perceived causes of the error and views about EP; they were audio-recorded and
      transcribed verbatim. Data were thematically analysed against a framework based
      on Reason's accident causation model, with a focus on identifying latent
      conditions. RESULTS: Twenty-five interviews explored causes of 32 errors. Slips
      and rule-based mistakes were the most common active failures. Error causation was
      multifactorial; environmental, individual, team, task and technology error
      producing conditions were all influenced by EP. There were three broad groups of
      latent conditions: the EP system's functionality and design; the organisation's
      decisions around EP implementation and use; and prescribing behaviours in the
      context of EP. CONCLUSIONS: Errors were associated with the design of EP itself
      and its integration within the healthcare environment. Findings suggest that EP
      vendors should focus on revolutionising interface design and usability issues,
      bearing in mind the wider healthcare context in which such software is used.
      Healthcare organisations should draw upon human factors principles when
      implementing EP. Consideration of work environment, infrastructure, training,
      prescribing responsibilities and behaviours should be considered to address local
      issues identified.

PMID- 29018056
TI  - Functional Genomics Approach Identifies Novel Signaling Regulators of TGFalpha
      Ectodomain Shedding.
AB  - Ectodomain shedding of cell-surface precursor proteins by metalloproteases
      generates important cellular signaling molecules. Of importance for disease is
      the release of ligands that activate the EGFR, such as TGFalpha, which is mostly
      carried out by ADAM17 [a member of the A-disintegrin and metalloprotease (ADAM)
      domain family]. EGFR ligand shedding has been linked to many diseases, in
      particular cancer development, growth and metastasis, as well as resistance to
      cancer therapeutics. Excessive EGFR ligand release can outcompete therapeutic
      EGFR inhibition or the inhibition of other growth factor pathways by providing
      bypass signaling via EGFR activation. Drugging metalloproteases directly have
      failed clinically because it indiscriminately affected shedding of numerous
      substrates. It is therefore essential to identify regulators for EGFR ligand
      cleavage. Here, integration of a functional shRNA genomic screen, computational
      network analysis, and dedicated validation tests succeeded in identifying several
      key signaling pathways as novel regulators of TGFalpha shedding in cancer cells.
      Most notably, a cluster of genes with NFkappaB pathway regulatory functions was
      found to strongly influence TGFalpha release, albeit independent of their
      NFkappaB regulatory functions. Inflammatory regulators thus also govern cancer
      cell growth-promoting ectodomain cleavage, lending mechanistic understanding to
      the well-known connection between inflammation and cancer.Implications: Using
      genomic screens and network analysis, this study defines targets that regulate
      ectodomain shedding and suggests new treatment opportunities for EGFR-driven
      cancers. Mol Cancer Res; 16(1); 147-61. (c)2017 AACR.

PMID- 29018059
TI  - Involvement of leptin in the molecular physiology of the placenta.
AB  - Leptin is a homeostatic regulator in the placenta where it promotes
      proliferation, protein synthesis and the expression of tolerogenic maternal
      response molecules such as HLA-G. Leptin also exerts an anti-apoptotic action in
      placenta controlling the expression of p53 master cell cycle regulator under
      different stress conditions. On the other hand, leptin is an integrative target
      of different placental stimuli. The expression of leptin in placenta is regulated
      by hCG, insulin, steroids, hypoxia and many other growth hormones, suggesting
      that it might have an important endocrine function in the trophoblastic cells.
      The leptin expression is induced involving the cAMP/PKA or cAMP/Epac pathways
      which have profound actions upon human trophoblast function. The activation of
      PI3K and MAPK pathways also participates in the leptin expression. Estrogens play
      a central role during pregnancy, particularly 17beta-estradiol upregulates the
      leptin expression in placental cells through genomic and non-genomic actions. The
      leptin promoter analysis reveals specific elements that are active in placental
      cells. The transcription factors CREB, AP1, Sp1, NFkappaB and the coactivator CBP
      are involved in the placental leptin expression. Moreover, placental leptin
      promoter is a target of epigenetic marks such as DNA methylation and histone
      acetylation that regulates not only the leptin expression in placenta during
      pregnancy but also determines the predisposition of acquiring adult metabolism
      diseases. Taken together, all these results allow a better understanding of
      leptin function and regulatory mechanisms of leptin expression in human placental
      trophoblasts, and support the importance of leptin during pregnancy and in
      programming adult health.

PMID- 29018057
TI  - PD-1 Blockade Prevents the Development and Progression of Carcinogen-Induced Oral
      Premalignant Lesions.
AB  - Oral squamous cell carcinoma (OSCC) is preceded by progressive oral premalignant
      lesions (OPL). Therefore, therapeutic strategies that prevent malignant
      progression of OPLs are expected to reduce the incidence of OSCC development.
      Immune checkpoint inhibitors that target the interaction of programmed death
      receptor 1 (PD-1) on T cells with the PD-1 ligand PD-L1 on cancer cells have been
      shown to extend the survival of patients with advanced OSCC. Here, we used the 4
      nitroquinoline-1-oxide (4-NQO) mouse model of oral carcinogenesis to test the
      hypothesis that PD-1 blockade may control the progression of OPLs. Mice were
      exposed to 4-NQO in their drinking water and then randomly assigned to two
      treatment groups that received either a blocking antibody for PD-1 or a control
      IgG. We found that anti-PD-1 treatment significantly reduced the number of oral
      lesions that developed in these mice and prevented malignant progression. Low
      grade dysplastic lesions responded to PD-1 blockade with a significant increase
      in the recruitment of CD8+ and CD4+ T cells and the accumulation of CTLA-4+ T
      cells in their microenvironment. Notably, PD-1 inhibition was accompanied by
      induction of IFNgamma, STAT1 activation and the production of the T-cell effector
      granzyme B in infiltrating cells, and by the induction of apoptosis in the
      epithelial cells of the oral lesions, suggesting that T-cell activation mediates
      the immunopreventive effects of anti-PD-1. These results support the potential
      clinical benefit of PD-1 immune checkpoint blockade to prevent OSCC development
      and progression and suggest that CTLA-4 inhibitors may enhance the preventive
      effects of anti-PD-1. Cancer Prev Res; 10(12); 684-93. (c)2017 AACRSee related
      editorial by Gutkind et al., p. 681.

PMID- 29018061
TI  - Association between MRI-defined osteoarthritis, pain, function and strength 3-10
      years following knee joint injury in youth sport.
AB  - BACKGROUND: Youth and young adults who participate in sport have an increased
      risk of knee injury and subsequent osteoarthritis. Improved understanding of the
      relationship between structural and clinical outcomes postinjury could inform
      targeted osteoarthritis prevention interventions. This secondary analysis
      examines the association between MRI-defined osteoarthritis and self-reported and
      functional outcomes, 3-10 years following youth sport-related knee injury in
      comparison to healthy controls. METHODS: Participants included a subsample
      (n=146) of the Alberta Youth Prevention of Early Osteoarthritis cohort:
      specifically, 73 individuals with 3-10years history of sport-related intra
      articular knee injury and 73 age-matched, sex-matched and sport-matched controls
      with completed MRI studies. Outcomes included: MRI-defined osteoarthritis,
      radiographic osteoarthritis, Knee Injury and Osteoarthritis Outcome Score,
      Intermittent and Constant Osteoarthritis Pain, knee extensor/flexor strength,
      triple-hop and Y-balance test. Descriptive statistics and univariate logistic
      regression were used to compare those with and without MRI-defined
      osteoarthritis. Associations between MRI-defined osteoarthritis and each outcome
      were assessed using multivariable linear regression considering the influence of
      injury history, sex, body mass index and time since injury. RESULTS: Participant
      median age was 23 years (range 15-27), and 63% were female. MRI-defined
      osteoarthritis varied by injury history, injury type and surgical history and was
      not isolated to participants with ACL and/or meniscal injuries. Those with a
      previous knee injury had 10-fold (95% CI 2.3 to 42.8) greater odds of MRI-defined
      osteoarthritis than uninjured participants. MRI-defined osteoarthritis was
      independently significantly associated with quality of life, but not symptoms,
      strength or function. SUMMARY: MRI-detected structural changes 3- 10 years
      following youth sport-related knee injury may not dictate clinical
      symptomatology, strength or function but may influence quality of life.

PMID- 29018060
TI  - Dietary supplements for treating osteoarthritis: a systematic review and meta
      analysis.
AB  - OBJECTIVE: To investigate the efficacy and safety of dietary supplements for
      patients with osteoarthritis. DESIGN: An intervention systematic review with
      random effects meta-analysis and meta-regression. DATA SOURCES: MEDLINE, EMBASE,
      Cochrane Register of Controlled Trials, Allied and Complementary Medicine and
      Cumulative Index to Nursing and Allied Health Literature were searched from
      inception to April 2017. STUDY ELIGIBILITY CRITERIA: Randomised controlled trials
      comparing oral supplements with placebo for hand, hip or knee osteoarthritis.
      RESULTS: Of 20 supplements investigated in 69 eligible studies, 7 (collagen
      hydrolysate, passion fruit peel extract, Curcuma longa extract, Boswellia serrata
      extract, curcumin, pycnogenol and L-carnitine) demonstrated large (effect size
      >0.80) and clinically important effects for pain reduction at short term. Another
      six (undenatured type II collagen, avocado soybean unsaponifiables,
      methylsulfonylmethane, diacerein, glucosamine and chondroitin) revealed
      statistically significant improvements on pain, but were of unclear clinical
      importance. Only green-lipped mussel extract and undenatured type II collagen had
      clinically important effects on pain at medium term. No supplements were
      identified with clinically important effects on pain reduction at long term.
      Similar results were found for physical function. Chondroitin demonstrated
      statistically significant, but not clinically important structural improvement
      (effect size -0.30, -0.42 to -0.17). There were no differences between
      supplements and placebo for safety outcomes, except for diacerein. The Grading of
      Recommendations Assessment, Development and Evaluation suggested a wide range of
      quality evidence from very low to high. CONCLUSIONS: The overall analysis
      including all trials showed that supplements provided moderate and clinically
      meaningful treatment effects on pain and function in patients with hand, hip or
      knee osteoarthritis at short term, although the quality of evidence was very low.
      Some supplements with a limited number of studies and participants suggested
      large treatment effects, while widely used supplements such as glucosamine and
      chondroitin were either ineffective or showed small and arguably clinically
      unimportant treatment effects. Supplements had no clinically important effects on
      pain and function at medium-term and long-term follow-ups.

PMID- 29018062
TI  - Gastrointestinal symptoms in elite athletes: time to recognise the problem?

PMID- 29018063
TI  - Scapular dyskinesis and shoulder pain: the devil is in the detail.

PMID- 29018065
TI  - Prevalence and associated factors of active smoking among individuals living with
      hypertension and/or diabetes in Africa: a systematic review and meta-analysis
      protocol.
AB  - INTRODUCTION: Tobacco use significantly increases cardiovascular complications in
      people living with hypertension and/or diabetes. We aim to summarise data on the
      prevalence and factors associated with active smoking in these conditions in
      Africa. METHOD AND ANALYSIS: We will search PubMed, Embase, Google Scholar and
      African Journals Online for relevant abstracts of studies on active smoking in
      individuals living with diabetes and/or hypertension published from 1 January
      2000 to 31 December 2016, with no language restriction. Additionally, relevant
      unpublished papers and conference proceedings will be checked, as well as
      references of included articles. Two investigators will independently screen,
      select studies, extract data and assess the risk of bias in each study. Data will
      be analysed using Stata software (Stata V.14, Texas, USA). The study-specific
      estimates will be pooled through a random-effects meta-analysis model to obtain
      an overall summary estimate of the prevalence of smoking across studies. Also, we
      will assess factors associated to smoking. Heterogeneity of studies will be
      evaluated by the chi2 test on Cochrane's Q statistic. Funnel plots analysis and
      Egger's test will be done to detect publication bias. Results will be presented
      by geographic region (central, eastern, northern, southern and western Africa). A
      p value less than 0.05 will be considered significant for factors associated to
      smoking. ETHICS AND DISSEMINATION: This study is based on published data, and
      therefore ethical approval is not a requirement. This systematic review and meta
      analysis is expected to serve as a basis for designing cost-effective
      interventions to reduce and prevent smoking in patients with diabetes and/or
      hypertension, and as a guide for future research based on the remaining gaps. The
      final report of this study in the form of a scientific paper will be published in
      peer-reviewed journals. Findings will further be presented at conferences and
      submitted to relevant health authorities.

PMID- 29018066
TI  - Pilot study for the registry of complications in rheumatic diseases from the
      German Society of Surgery (DGORh): evaluation of methods and data from the first
      1000 patients.
AB  - OBJECTIVE: Most patients suffering with rheumatic diseases who undergo surgical
      treatment are receiving immune-modulating therapy. To determine whether these
      medications affect their outcomes a national registry was established in Germany
      by the German Society of Surgery (DGORh). Data from the first 1000 patients were
      used in a pilot study to identify relevant corisk factors and to determine
      whether such a registry is suitable for developing accurate and relevant
      recommendations. DESIGN AND PARTICIPANTS: Data were collected from patients
      undergoing surgical treatments with their written consent. A second consent form
      was used, if complications occurred. During this pilot study, in order to obtain
      a quicker overview, risk factors were considered only in patients with
      complications. Only descriptive statistical analysis was employed in this pilot
      study due to limited number of observed complications and inhomogeneous data
      regarding the surgery and the medications the patients received. Analytical
      statistics will be performed to confirm the results in a future outcome study.
      RESULTS: Complications occurred in 26 patients and were distributed equally among
      the different types of surgeries. Twenty one of these patients were receiving
      immune-modulating therapy at the time, while five were not. Infections were
      observed in 2.3% of patients receiving and in 5.1% not receiving
      immunosuppression. CONCLUSIONS: Due to the low number of cases, inhomogeneity in
      the diseases and the treatments received by the patients in this pilot study, it
      is not possible to develop standardised best-practice recommendations to optimise
      their care. Based on this observation we conclude that in order to be suitable to
      develop accurate and relevant recommendations a national registry must include
      the most important and relevant variables that impact the care and outcomes of
      these patients.

PMID- 29018064
TI  - Psychoeducational intervention for people at high risk of developing another
      melanoma: a pilot randomised controlled trial.
AB  - INTRODUCTION: Information and psychological needs have been reported as one of
      the greatest areas of unmet needs for patients with melanoma. To respond to these
      needs, we developed the Melanoma Care Intervention, a developed psychoeducational
      intervention for people at high risk of developing another melanoma comprising of
      a newly developed melanoma educational booklet and individually tailored
      telephone support sessions provided by trained psychologists. The purpose of this
      study was to investigate the acceptability and feasibility of the Melanoma Care
      Intervention. METHODS: Twenty-four adults (14 men, 10 women, mean age: 58 years,
      SD: 12.2) at high risk of developing a subsequent primary melanoma were recruited
      and randomly assigned 1:1 to the intervention (a psychoeducational booklet, a
      Cancer Council booklet on melanoma and up to five telephone-based sessions with a
      psychologist) or usual care (Cancer Council booklet only). Acceptability,
      feasibility, fear of cancer recurrence and secondary psychosocial outcomes were
      assessed at baseline, 1 and 6 months. RESULTS: Satisfaction and perceived
      benefits were rated highly for all intervention components, particularly the
      telephone-based psychology sessions (mean satisfaction and benefits: both 9.27
      out of 10, SD=2.41). The quality of information and support provided throughout
      the trial was rated as 'high' by the intervention group, with a mean score of 4.6
      out of a possible 5 (SD=0.9) and 4.2 (SD=1.2) for the control group. CONCLUSIONS:
      The intervention was feasible and acceptable for improving psychological
      adjustment. Timely access to effective, evidence-based, psychological care is a
      recognised need for people with melanoma. The intervention is designed to
      directly address this need in a way that is feasible in a clinical setting,
      acceptable to patients and health professionals. TRIAL REGISTRATION NUMBER: The
      trial was registered with the Australian and New Zealand Clinical Trials Registry
      on 19/03/2013 (Registration Number: ACTRN12613000304730).

PMID- 29018067
TI  - Post-abortion care with misoprostol - equally effective, safe and accepted when
      administered by midwives compared to physicians: a randomised controlled
      equivalence trial in a low-resource setting in Kenya.
AB  - OBJECTIVE: To assess the effectiveness of midwives administering misoprostol to
      women with incomplete abortion seeking post-abortion care (PAC), compared with
      physicians. DESIGN: A multicentre randomised controlled equivalence trial. The
      study was not masked. SETTINGS: Gynaecological departments in two hospitals in a
      low-resource setting, Kenya. POPULATION: Women (n=1094) with incomplete abortion
      in the first trimester, seeking PAC between 1 June 2013 to 31 May 2016.
      Participants were randomly assigned to receive treatment from midwives or
      physicians. 409 and 401 women in the midwife and physician groups, respectively,
      were included in the per-protocol analysis. INTERVENTIONS: 600 ug misoprostol
      orally, and contraceptive counselling by a physician or midwife. MAIN OUTCOME
      MEASURES: Complete abortion not needing surgical intervention within 7-10 days.
      The main outcome was analysed on the per-protocol population with a generalised
      estimating equation model. The predefined equivalence range was -4% to 4%.
      Secondary outcomes were analysed descriptively. RESULTS: The proportion of
      complete abortion was 94.8% (768/810): 390 (95.4%) in the midwife group and 378
      (94.3%) in the physician group. The proportion of incomplete abortion was 5.2%
      (42/810), similarly distributed between midwives and physicians. The model-based
      risk difference for midwives versus physicians was 1.0% (-4.1 to 2.2). Most women
      felt safe (97%; 779/799), and 93% (748/801) perceived the treatment as
      expected/easier than expected. After contraceptive counselling the uptake of a
      contraceptive method after 7-10 days occurred in 76% (613/810). No serious
      adverse events were recorded. CONCLUSIONS: Treatment of incomplete abortion with
      misoprostol provided by midwives is equally effective, safe and accepted by women
      as when administered by physicians in a low-resource setting. Systematically
      provided contraceptive counselling in PAC is effective to mitigate unmet need for
      contraception. TRIAL REGISTRATION NUMBER: NCT01865136; Results.

PMID- 29018068
TI  - Epidemiology of venous thromboembolism in Africa: a systematic review and meta
      analysis protocol.
AB  - INTRODUCTION: Venous thromboembolism (VTE) is among the three major causes of
      cardiovascular diseases worldwide after ischaemic heart disease and stroke.
      Knowledge on the global epidemiology of this condition is deficient in Africa.
      Accurate data are needed to evaluate the burden of VTE in Africa to design
      effective preventive and treatment strategies. This systematic review and meta
      analysis aims to summarise epidemiological data on VTE in Africa and to evaluate
      the use of prophylaxis in African patients at risk of VTE. METHODS AND ANALYSIS:
      Medline, Embase, Scopus and African Journal Online will be searched for relevant
      abstracts of studies published between 1 January 1986 and 5 December 2016,
      without language restriction. After a screening of abstracts, study selection,
      data extraction and assessment of the risk of bias, we shall assess studies
      individually for clinical and statistical heterogeneity. Appropriate meta
      analytic technics will then be used to pool studies judged to be clinically
      homogeneous. Funnel-plots analysis and Egger's test will be used to detect
      publication bias. Results will be presented by geographical region (Central,
      Eastern, Northern, Southern and Western Africa). This systematic review will be
      reported according to the Meta-analysis of Observational Studies in Epidemiology
      Guidelines. ETHICS AND DISSEMINATION: The current study will be based on
      published data, and thus ethics consideration is not required. This review is
      expected to provide relevant data to help in quantifying the magnitude of this
      disease in Africa. The final report of this study will be published in a peer
      reviewed journal and the findings will be submitted to relevant health
      authorities. TRIAL REGISTRATION NUMBER: The protocol for this review has been
      published in the International Prospective Register of systematic reviews
      (http://www.crd.york.ac.uk/PROSPERO), registration number: PROSPERO
      CRD42017056253.

PMID- 29018071
TI  - Effects of family planning factors on the awareness of sexual and reproductive
      healthcare rights among married women of reproductive age in China: a cross
      sectional study.
AB  - OBJECTIVES: Although family planning in China has changed gradually since 1994,
      there are few studies about family planning and women's reproductive rights. The
      main objective of this study was to examine awareness of sexual and reproductive
      healthcare rights (SRHCRs), and learn how factors related to family planning
      influence awareness of SRHCRs among married women of reproductive age in China.
      METHODS AND PARTICIPANTS: Inner Mongolia, Chongqing, Guangdong and Henan were
      selected for the study, and a total of 2504 married women of reproductive age
      were recruited. A self-administered anonymous questionnaire was used to collect
      information on participants' awareness of SRHCRs. RESULTS: There were a total of
      10 843 (<=6*2504) responses, with a response rate of 72.17% (10 843/15 024) on
      average among participants regarding SRHCRs (a multiple response set). The
      highest response rate was for choice (Right 3) (90.64%, 95% CI 89.47%, 91.81%),
      followed by privacy (Right 5) (86.11%, 95% CI 84.72%, 87.50%) and information
      (Right 1) (84.47%, 95% CI 83.02%, 85.93%). Only 43.39% (95% CI 41.40%, 45.38%) of
      participants gave responses to safety (Right 4). Participants without children
      showed more interest in Right 1, in access (Right 2) and in Right 4. Those who
      utilised tests for fetal sex determination paid more attention to Rights 2 and 4.
      Women who accepted informed choice were more likely to be aware of all six rights
      except for Right 3 and dignity (Right 6). Those individuals who were satisfied or
      very satisfied with comprehensive sexual and reproductive health counselling
      services were more likely to show interest in all six rights. CONCLUSIONS:
      Awareness of SRHCRs among reproductive aged women in China is still inadequate.
      Family planning service providers might strengthen the service awareness of sex
      and reproductive health rights according to the different needs of women.

PMID- 29018069
TI  - Using comprehensive geriatric assessment for quality improvements in healthcare
      of older people in UK care homes: protocol for realist review within Proactive
      Healthcare of Older People in Care Homes (PEACH) study.
AB  - INTRODUCTION: Care home residents are relatively high users of healthcare
      resources and may have complex needs. Comprehensive geriatric assessment (CGA)
      may benefit care home residents and improve efficiency of care delivery. This is
      an approach to care in which there is a thorough multidisciplinary assessment
      (physical and mental health, functioning and physical and social environments)
      and a care plan based on this assessment, usually delivered by a
      multidisciplinary team. The CGA process is known to improve outcomes for
      community-dwelling older people and those in receipt of hospital care, but less
      is known about its efficacy in care home residents. METHODS AND ANALYSIS: Realist
      review was selected as the most appropriate method to explore the complex nature
      of the care home setting and multidisciplinary delivery of care. The aim of the
      realist review is to identify and characterise a programme theory that underpins
      the CGA intervention. The realist review will extract data from research articles
      which describe the causal mechanisms through which the practice of CGA generates
      outcomes. The focus of the intervention is care homes, and the outcomes of
      interest are health-related quality of life and satisfaction with services; for
      both residents and staff. Further outcomes may include appropriate use of
      National Health Service services and resources of older care home residents. The
      review will proceed through three stages: (1) identifying the candidate programme
      theories that underpin CGA through interviews with key stakeholders, systematic
      search of the peer-reviewed and non-peer-reviewed evidence, (2) identifying the
      evidence relevant to CGA in UK care homes and refining the programme theories
      through refining and iterating the systematic search, lateral searches and
      seeking further information from study authors and (3) analysis and synthesis of
      evidence, involving the testing of the programme theories. ETHICS AND
      DISSEMINATION: The PEACH project was identified as service development following
      submission to the UK Health Research Authority and subsequent review by the
      University of Nottingham Research Ethics Committee. The study protocols have been
      reviewed as part of good governance by the Nottinghamshire Healthcare Foundation
      Trust. We aim to publish this realist review in a peer-reviewed journal with
      international readership. We will disseminate findings to public and stakeholders
      using knowledge mobilisation techniques. Stakeholders will include the Quality
      Improvement Collaboratives within PEACH study. National networks, such as British
      Society of Gerontology and National Care Association will be approached for wider
      dissemination. TRIAL REGISTRATION NUMBER: The realist review has been registered
      on International Prospective Register of Systematic Reviews (PROSPERO 2017:
      CRD42017062601).

PMID- 29018070
TI  - Hypothermic oxygenated machine perfusion (HOPE) for orthotopic liver
      transplantation of human liver allografts from extended criteria donors (ECD) in
      donation after brain death (DBD): a prospective multicentre randomised controlled
      trial (HOPE ECD-DBD).
AB  - INTRODUCTION: Orthotopic liver transplantation (OLT) has emerged as the mainstay
      of treatment for end-stage liver disease. In an attempt to improve the
      availability of donor allografts and reduce waiting list mortality, graft
      acceptance criteria were extended increasingly over the decades. The use of
      extended criteria donor (ECD) allografts is associated with a higher incidence of
      primary graft non-function and/or delayed graft function. As such, several
      strategies have been developed aiming at reconditioning poor quality ECD liver
      allografts. Hypothermic oxygenated machine perfusion (HOPE) has been successfully
      tested in preclinical experiments and in few clinical series of donation after
      cardiac death OLT. METHODS AND ANALYSIS: HOPE ECD-DBD is an investigator
      initiated, open-label, phase-II, prospective multicentre randomised controlled
      trial on the effects of HOPE on ECD allografts in donation after brain death
      (DBD) OLT. Human whole organ liver grafts will be submitted to 1-2 hours of HOPE
      (n=23) via the portal vein before implantation and are going to be compared with
      a control group (n=23) of patients transplanted after conventional cold storage.
      Primary (peak and Delta peak alanine aminotransferase within 7 days) and
      secondary (aspartate aminotransferase, bilirubin and international normalised
      ratio, postoperative complications, early allograft dysfunction, duration of
      hospital and intensive care unit stay, 1-year patient and graft survival)
      endpoints will be analysed within a 12-month follow-up. Extent of ischaemia
      reperfusion (I/R) injury will be assessed using liver tissue, perfusate, bile and
      serum samples taken during the perioperative phase of OLT. ETHICS AND
      DISSEMINATION: The study was approved by the institutional review board of the
      RWTH Aachen University, Aachen, Germany (EK 049/17). The current paper represent
      the pre-results phase. First results are expected in 2018. TRIAL REGISTRATION
      NUMBER: NCT03124641.

PMID- 29018072
TI  - Association between home visiting interventions and First Nations families'
      health and social outcomes in Manitoba, Canada: protocol for a study of linked
      population-based administrative data.
AB  - INTRODUCTION: First Nations people are descendants of Canada's original
      inhabitants. In consequence of historical and ongoing structural injustices, many
      First Nations families struggle with challenging living conditions, including
      high rates of poverty, poor housing conditions, mental illness and social
      isolation. These risk factors impede caregivers' abilities to meet their
      children's basic physical and psychosocial needs. Home visiting programmes were
      developed to support child developmental health in families facing parenting
      challenges. However, whether home visiting is an effective intervention for First
      Nations families has not been examined. We are evaluating two home visiting
      programmes in Manitoba, Canada, to determine whether they promote nurturing
      family environments for First Nations children. METHODS AND ANALYSIS: This
      research builds on new and established relationships among academic researchers,
      government decision-makers and First Nations stakeholders. We will link health,
      education and social services data from the Manitoba Population Research Data
      Repository to data from two home visiting programmes in Manitoba. Logistic
      regression modelling will be used to assess whether programme participation is
      associated with improved child developmental health, better connections between
      families and social services, reduced instances of child maltreatment and being
      taken into out-of-home care by child welfare and reduced inequities for First
      Nations families. Non-participating individuals with similar sociodemographic
      characteristics will serve as comparators. We will use an interrupted time series
      approach to test for differences in outcomes before and after programme
      implementation and a propensity score analysis to compare differences between
      participants and non-participants. ETHICS AND DISSEMINATION: Approvals were
      granted by the Health Information Research Governance Committee of the First
      Nations Health and Social Secretariat of Manitoba and the University of Manitoba
      Health Research Ethics Board. Our integrated knowledge translation approach will
      involve disseminating findings through government and community briefings,
      developing lay summaries and infographics, presenting at academic conferences and
      publishing in scientific journals.

PMID- 29018073
TI  - Seasonal influenza vaccine effectiveness against laboratory-confirmed influenza
      in 2015-2016: a hospital-based test-negative case-control study in Lithuania.
AB  - OBJECTIVE: A case-control study was conducted to assess seasonal influenza
      vaccine effectiveness (SIVE) during the 2015-2016 influenza season. METHODS: A
      study was performed in three departments in Lithuania between 1 December 2015 and
      1 May 2016. Data on demographic and clinical characteristics including influenza
      vaccination status were collected from the patients recommended to receive the
      seasonal influenza vaccine. Influenza virus infection was confirmed by multiplex
      reverse transcription polymerase chain reaction (RT-PCR) . RESULTS: Ninety-one
      (56.4%) of the 163 included subjects were >=65 years old. Fifteen (9.2%) subjects
      were vaccinated against influenza at least 2 weeks before the onset of influenza
      symptoms, 12 of them were >=65 years old. Of the 72 (44.2%) influenza virus
      positive cases, 65 (39.9%) were confirmed with influenza A (including 50 cases of
      influenza A(H1N1)pdm09), eight (4.9%) were confirmed with influenza B and one was
      a co-infection. Unadjusted SIVE against any influenza, influenza type A and
      influenza A(H1N1)pdm09 was 57% (95% CI -41% to 87%), 52% (95% CI -57% to 85%) and
      70% (95% CI -43% to 94%) respectively. CONCLUSION: Although SIVE estimates were
      not statistically significant the point estimates suggest moderate effectiveness
      against influenza type A.

PMID- 29018074
TI  - Organisational and extraorganisational determinants of volume of service delivery
      by English community pharmacies: a cross-sectional survey and secondary data
      analysis.
AB  - OBJECTIVES: This study aimed to identify the organisational and
      extraorganisational factors associated with existing variation in the volume of
      services delivered by community pharmacies. DESIGN AND SETTING: Linear and
      ordered logistic regression of linked national data from secondary sources
      community pharmacy activity, socioeconomic and health need datasets-and primary
      data from a questionnaire survey of community pharmacies in nine diverse
      geographical areas in England. OUTCOME MEASURES: Annual dispensing volume; annual
      volume of medicines use reviews (MURs). RESULTS: National dataset (n=10 454
      pharmacies): greater dispensing volume was significantly associated with pharmacy
      ownership type (large chains>independents>supermarkets), greater deprivation,
      higher local prevalence of cardiovascular disease and depression, older people
      (aged >75 years) and infants (aged 0-4 years) but lower prevalence of mental
      health conditions. Greater volume of MURs was significantly associated with
      pharmacy ownership type (large chains/supermarkets>>independents), greater
      dispensing volume, and lower disease prevalence.Survey dataset (n=285 pharmacies;
      response=34.6%): greater dispensing volume was significantly associated with
      staffing, skill-mix, organisational culture, years open and greater deprivation.
      Greater MUR volume was significantly associated with pharmacy ownership type
      (large chains/supermarkets>>independents), greater dispensing volume, weekly
      opening hours and lower asthma prevalence. CONCLUSIONS: Organisational and
      extraorganisational factors were found to impact differently on dispensing volume
      and MUR activity, the latter being driven more by corporate ownership than
      population need. While levels of staffing and skill-mix were associated with
      dispensing volume, they did not influence MUR activity. Despite recent changes to
      the contractual framework, the existing fee-for-service reimbursement may
      therefore not be the most appropriate for the delivery of cognitive (rather than
      supply) services, still appearing to incentivise quantity over the quality (in
      terms of appropriate targeting) of services delivered. Future research should
      focus on the development of quality measures that could be incorporated into
      community pharmacy reimbursement mechanisms.

PMID- 29018075
TI  - Prospective Investigation of Pesticide Applicators' Health (PIPAH) study: a
      cohort study of professional pesticide users in Great Britain.
AB  - PURPOSE: The purpose of the study is to monitor the exposure and health of
      workers in Great Britain who use pesticides as a part of their job, and to gain a
      better understanding of the relationship between long-term exposure to pesticides
      and health. PARTICIPANTS: Study participants are professional pesticide users who
      are certified in the safe use of pesticides or who were born before 1965 and
      apply pesticides under 'grandfather rights'. Overall response rate was 20%;
      participants are mostly male (98%) and the average age is 54 years, ranging from
      17 to over 80 years. FINDINGS TO DATE: Participants have completed a baseline
      general questionnaire and three follow-up questionnaires on the use of
      pesticides. These data will enable investigations into the relationship between
      occupational pesticide exposure and health outcomes taking into account non
      occupational confounding factors. FUTURE PLANS: There is no set end date for data
      collection. Recruitment into the cohort will continue, and for the foreseeable
      future there will be annual pesticide use questionnaires and five yearly follow
      up general questionnaires.The intention is to validate the pesticide use
      questionnaire, and to develop a crop/job exposure matrix (C/JEM) which can be
      updated regularly. This C/JEM will be able to look at general categories of
      pesticide, such as insecticides, structurally related pesticides, such as
      organochlorines, or individual active ingredients. Data collected on use of
      personal protective equipment and method of application will provide information
      on how potential exposure to pesticide during application may have been modified.
      The study will be able to estimate changes in individual pesticide use over time,
      and to examine the associations between pesticide use and both baseline and long
      term health outcomes.The cohort members will be linked to national databases for
      notification of hospital episode statistics, cancer incidence and mortality for
      follow-up of health outcomes.

PMID- 29018076
TI  - Protocol for a prospective interventional trial to develop a diagnostic index
      test for stroke as a cause of vertigo, dizziness and imbalance in the emergency
      room (EMVERT study).
AB  - INTRODUCTION: Identifying stroke as a cause of acute vertigo, dizziness and
      imbalance in the emergency room is still a clinical challenge. Many patients are
      admitted to stroke units, but only a minority will have strokes. This imposes a
      heavy financial burden on the healthcare system. The aim of this study is to
      develop a diagnostic index test to identify patients with a high risk of having a
      stroke as the cause of acute vertigo and imbalance. METHODS AND ANALYSIS:
      Patients with acute onset of vertigo, dizziness, postural imbalance or double
      vision within the last 24 hours lasting for at least 10 min are eligible to be
      included in the study. Patients with clinically proven peripheral or central
      aetiology will be excluded. In the emergency room, all enrolled patients will
      undergo standardised neuro-ophthalmological/physiological testing (including
      video-oculography, mobile posturography, measurement of subjective visual
      vertical) (EMVERT block 1). Within 10 days, standardised MRI will be performed as
      a reference test to identify stroke (EMVERT block 2). Data from EMVERT block 2
      will be compared with results from block 1 in order to devise a diagnostic index
      test with a high specificity and sensitivity to predict the risk of stroke in the
      emergency room. ETHICS AND DISSEMINATION: The study was approved by the ethics
      committee of the University of Munich and will be conducted according to the
      Guideline for Good Clinical Practice, the Federal Data Protecting Act and the
      Helsinki Declaration of the World Medical Association in its recent version.
      Study results are expected to be published in international peer-reviewed
      journals and will be presented at international conferences. TRIAL REGISTRATION
      NUMBER: German Clinical Trial Register: DRKS00008992; Universal trial number:
      U1111-1172-8719); pre-results.

PMID- 29018077
TI  - Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14)
      multiple myeloma.
AB  - Venetoclax is a selective, orally bioavailable BCL-2 inhibitor that induces cell
      death in multiple myeloma (MM) cells, particularly in those harboring t(11;14),
      which express high levels of BCL-2 relative to BCL-XL and MCL-1. In this phase 1
      study, patients with relapsed/refractory MM received venetoclax monotherapy.
      After a 2-week lead-in with weekly dose escalation, daily venetoclax was given at
      300, 600, 900, or 1200 mg in dose-escalation cohorts and 1200 mg in the safety
      expansion. Dexamethasone could be added on progression during treatment. Sixty
      six patients were enrolled (30, dose-escalation cohorts; 36, safety expansion).
      Patients received a median of 5 prior therapies (range, 1-15); 61% were
      bortezomib and lenalidomide double refractory, and 46% had t(11;14). Venetoclax
      was generally well tolerated. Most common adverse events included mild
      gastrointestinal symptoms (nausea [47%], diarrhea [36%], vomiting [21%]).
      Cytopenias were the most common grade 3/4 events, with thrombocytopenia (32%),
      neutropenia (27%), anemia (23%), and leukopenia (23%) reported. The overall
      response rate (ORR) was 21% (14/66), and 15% achieved very good partial response
      or better (>=VGPR). Most responses (12/14 [86%]) were reported in patients with
      t(11;14). In this group, ORR was 40%, with 27% of patients achieving >=VGPR.
      Biomarker analysis confirmed that response to venetoclax correlated with higher
      BCL2:BCL2L1 and BCL2:MCL1 mRNA expression ratios. Venetoclax monotherapy at a
      daily dose up to 1200 mg has an acceptable safety profile and evidence of single
      agent antimyeloma activity in patients with relapsed/refractory MM, predominantly
      in patients with t(11;14) abnormality and those with a favorable BCL2 family
      profile. Registered at www.clinicaltrials.gov: #NCT01794520.

PMID- 29018078
TI  - Novel approaches to hemophilia therapy: successes and challenges.
AB  - New therapies for hemophilia A and hemophilia B will likely continue to change
      clinical practice. Ranging from extended half-life to nonfactor products and gene
      therapy, these innovative approaches have the potential to enhance the standard
      of care by decreasing infusion frequency to increase compliance, promoting
      prophylaxis, offering alternatives to inhibitor patients, and easing route of
      administration. Each category has intrinsic challenges that may limit the broader
      application of these promising therapies. To date, none specifically address the
      challenge of dispersing treatment to the developing world.

PMID- 29018081
TI  - Platelet interaction with activated endothelium: mechanistic insights from
      microfluidics.
AB  - Traditionally, in vitro flow chamber experiments and in vivo arterial thrombosis
      studies have been proved to be of vital importance to elucidate the mechanisms of
      platelet thrombus formation after vessel wall injury. In recent years, it has
      become clear that platelets also act as modulators of inflammatory processes,
      such as atherosclerosis. A key element herein is the complex cross talk between
      platelets, the coagulation system, leukocytes, and the activated endothelium.
      This review provides insight into the platelet-endothelial interface, based on in
      vitro flow chamber studies and cross referenced with in vivo thrombosis studies.
      The main mechanisms of platelet interaction with the activated endothelium
      encompass (1) platelet rolling via interaction of platelet glycoprotein Ib-IX-V
      with endothelial-released von Willebrand factor with a supporting role for the P
      selectin/P-selectin glycoprotein ligand 1 axis, followed by (2) firm platelet
      adhesion to the endothelium via interaction of platelet alphaIIbbeta3 with
      endothelial alphavbeta3 and intercellular adhesion molecule 1, and (3) a
      stimulatory role for thrombin, the thrombospondin-1/CD36 axis and cyclooxygenase
      1 in subsequent platelet activation and stable thrombus formation. In addition,
      the molecular mechanisms underlying the stimulatory effect of platelets on
      leukocyte transendothelial migration, a key mediator of atheroprogression, are
      discussed. Throughout the review, emphasis is placed on recommendations for
      setting up, reporting, interpreting, and comparing endothelial-lined flow chamber
      studies and suggestions for future studies.

PMID- 29018079
TI  - SETD2 alterations impair DNA damage recognition and lead to resistance to
      chemotherapy in leukemia.
AB  - Mutations in SETD2, encoding the histone 3 lysine 36 trimethyltransferase, are
      enriched in relapsed acute lymphoblastic leukemia and MLL-rearranged acute
      leukemia. We investigated the impact of SETD2 mutations on chemotherapy
      sensitivity in isogenic leukemia cell lines and in murine leukemia generated from
      a conditional knockout of Setd2. SETD2 mutations led to resistance to DNA
      damaging agents, cytarabine, 6-thioguanine, doxorubicin, and etoposide, but not
      to a non-DNA damaging agent, l-asparaginase. H3K36me3 localizes components of the
      DNA damage response (DDR) pathway and SETD2 mutation impaired DDR, blunting
      apoptosis induced by cytotoxic chemotherapy. Consistent with local recruitment of
      DDR, genomic regions with higher H3K36me3 had a lower mutation rate, which was
      increased with SETD2 mutation. Heterozygous conditional inactivation of Setd2 in
      a murine model decreased the latency of MLL-AF9-induced leukemia and caused
      resistance to cytarabine treatment in vivo, whereas homozygous loss delayed
      leukemia formation. Treatment with JIB-04, an inhibitor of the H3K9/36me3
      demethylase KDM4A, restored H3K36me3 levels and sensitivity to cytarabine. These
      findings establish SETD2 alteration as a mechanism of resistance to DNA-damaging
      chemotherapy, consistent with a local loss of DDR, and identify a potential
      therapeutic strategy to target SETD2-mutant leukemias.

PMID- 29018080
TI  - Chd7 deficiency delays leukemogenesis in mice induced by Cbfb-MYH11.
AB  - Inversion of chromosome 16 is a consistent finding in patients with acute myeloid
      leukemia subtype M4 with eosinophilia, which generates a CBFB-MYH11 fusion gene.
      Previous studies showed that the interaction between CBFbeta-smooth muscle myosin
      heavy chain (SMMHC; encoded by CBFB-MYH11) and RUNX1 plays a critical role in the
      pathogenesis of this leukemia. Recently, it was shown that chromodomain helicase
      DNA-binding protein-7 (CHD7) interacts with RUNX1 and suppresses RUNX1-induced
      expansion of hematopoietic stem and progenitor cells. These results suggest that
      CHD7 is also critical for CBFB-MYH11-induced leukemogenesis. To test this
      hypothesis, we generated Chd7f/fMx1-CreCbfb+/56M mice, which expressed the Cbfb
      MYH11 fusion gene and deactivated Chd7 in hematopoietic cells upon inducing Cre
      with polyinosinic-polycytidylic acid. The Lin-Sca1-c-Kit+ (LK) population was
      significantly lower in Chd7f/fMx1-CreCbfb+/56M mice than in Mx1-CreCbfb+/56M
      mice. In addition, there were fewer 5-bromo-2'-deoxyuridine-positive cells in the
      LK population in Chd7f/fMx1-CreCbfb+/56M mice, and genes associated with cell
      cycle, cell growth, and proliferation were differentially expressed between
      Chd7f/fMx1-CreCbfb+/56M and Mx1-CreCbfb+/56M leukemic cells. In vitro studies
      showed that CHD7 interacted with CBFbeta-SMMHC through RUNX1 and that CHD7
      enhanced transcriptional activity of RUNX1 and CBFbeta-SMMHC on Csf1r, a RUNX1
      target gene. Moreover, RNA sequencing of c-Kit+ cells showed that CHD7 functions
      mostly through altering the expression of RUNX1 target genes. Most importantly,
      Chd7 deficiency delayed Cbfb-MYH11-induced leukemia in both primary and
      transplanted mice. These data indicate that Chd7 is important for Cbfb-MYH11
      induced leukemogenesis by facilitating RUNX1 regulation of transcription and
      cellular proliferation.

PMID- 29018083
TI  - Reviving a national prevention agenda is key to sustainability of health care in
      Canada.

PMID- 29018082
TI  - The orphan nuclear receptor TR4 regulates erythroid cell proliferation and
      maturation.
AB  - The orphan nuclear receptors TR4 (NR2C2) and TR2 (NR2C1) are the DNA-binding
      subunits of the macromolecular complex, direct repeat erythroid-definitive, which
      has been shown to repress epsilon- and gamma-globin transcription during adult
      definitive erythropoiesis. Previous studies implied that TR2 and TR4 act largely
      in a redundant manner during erythroid differentiation; however, during the
      course of routine genetic studies, we observed multiple variably penetrant
      phenotypes in the Tr4 mutants, suggesting that indirect effects of the mutation
      might be masked by multiple modifying genes. To test this hypothesis, Tr4+/-
      mutant mice were bred into a congenic C57BL/6 background and their phenotypes
      were reexamined. Surprisingly, we found that homozygous Tr4 null mutant mice
      expired early during embryogenesis, around embryonic day 7.0, and well before
      erythropoiesis commences. We further found that Tr4+/- erythroid cells failed to
      fully differentiate and exhibited diminished proliferative capacity. Analysis of
      Tr4+/- mutant erythroid cells revealed that reduced TR4 abundance resulted in
      decreased expression of genes required for heme biosynthesis and erythroid
      differentiation (Alad and Alas2), but led to significantly increased expression
      of the proliferation inhibitory factor, cyclin dependent kinase inhibitor
      (Cdkn1c) These studies support a vital role for TR4 in promoting erythroid
      maturation and proliferation, and demonstrate that TR4 and TR2 execute distinct,
      individual functions during embryogenesis and erythroid differentiation.

PMID- 29018085
TI  - Evaluating the effects of Quebec's private-public drug insurance system.

PMID- 29018086
TI  - Bitot spot: early marker for avoidable blindness.

PMID- 29018087
TI  - Natural health products are subjected to rigorous process prior to market.

PMID- 29018088
TI  - Natural health products, complementary and alternative medicine, and Health
      Canada.

PMID- 29018089
TI  - Hundreds of doctors support controversial tax reforms.

PMID- 29018090
TI  - Medical-legal concerns over prescribing opioids on the rise.

PMID- 29018084
TI  - Oral morphine versus ibuprofen administered at home for postoperative orthopedic
      pain in children: a randomized controlled trial.
AB  - BACKGROUND: Oral morphine for postoperative pain after minor pediatric surgery,
      while increasingly popular, is not supported by evidence. We evaluated whether
      oral morphine was superior to ibuprofen for at-home management of children's
      postoperative pain. METHODS: We conducted a randomized superiority trial
      comparing oral morphine (0.5 mg/kg) with ibuprofen (10 mg/kg) in children 5 to 17
      years of age who had undergone minor outpatient orthopedic surgery (June 2013 to
      September 2016). Participants took up to 8 doses of the intervention drug every 6
      hours as needed for pain at home. The primary outcome was pain, according to the
      Faces Pain Scale - Revised, for the first dose. Secondary outcomes included
      additional analgesic requirements, adverse effects, unplanned health care visits
      and pain scores for doses 2 to 8. RESULTS: We analyzed data for 77 participants
      in each of the morphine and ibuprofen groups. Both interventions decreased pain
      scores with no difference in efficacy. The median difference in pain score before
      and after the first dose of medication was 1 (interquartile range 0-1) for both
      morphine and ibuprofen (p = 0.2). For doses 2 to 8, the median differences in
      pain score before and after the dose were not significantly different between
      groups. Significantly more participants taking morphine reported adverse effects
      (45/65 [69%] v. 26/67 [39%], p < 0.001), most commonly drowsiness (31/65 [48%] v.
      15/67 [22%] in the morphine and ibuprofen groups, respectively; p = 0.003).
      INTERPRETATION: Morphine was not superior to ibuprofen, and both drugs decreased
      pain with no apparent difference in efficacy. Morphine was associated with
      significantly more adverse effects, which suggests that ibuprofen is a better
      first-line option after minor surgery. TRIAL REGISTRATION: ClinicalTrials.gov,
      no. NCT01686802.

PMID- 29018091
TI  - Sepsis kills one million newborns a year: WHO.

PMID- 29018092
TI  - Molecular characterization and verification of azido-3,8-dideoxy-d-manno-oct-2
      ulosonic acid incorporation into bacterial lipopolysaccharide.
AB  - 3-Deoxy-d-manno-oct-2-ulosonic acid (Kdo) is an essential component of LPS in the
      outer leaflet of the Gram-negative bacterial outer membrane. Although labeling of
      Escherichia coli with the chemical reporter 8-azido-3,8-dideoxy-d-manno-oct-2
      ulosonic acid (Kdo-N3) has been reported, its incorporation into LPS has not been
      directly shown. We have now verified Kdo-N3 incorporation into E. coli LPS at the
      molecular level. Using microscopy and PAGE analysis, we show that Kdo-N3 is
      localized to the outer membrane and specifically incorporates into rough and deep
      rough LPS. In an E. coli strain lacking endogenous Kdo biosynthesis,
      supplementation with exogenous Kdo restored full-length core-LPS, which suggests
      that the Kdo biosynthetic pathways might not be essential in vivo in the presence
      of sufficient exogenous Kdo. In contrast, exogenous Kdo-N3 only restored a small
      fraction of core LPS with the majority incorporated into truncated LPS. The
      truncated LPS were identified as Kdo-N3-lipid IVA and (Kdo-N3)2-lipid IVA by MS
      analysis. The low level of Kdo-N3 incorporation could be partly explained by a 6
      fold reduction in the specificity constant of the CMP-Kdo synthetase KdsB with
      Kdo-N3 compared with Kdo. These results indicate that the azido moiety in Kdo-N3
      interferes with its utilization and may limit its utility as a tracer of LPS
      biosynthesis and transport in E. coli We propose that our findings will be
      helpful for researchers using Kdo and its chemical derivatives for investigating
      LPS biosynthesis, transport, and assembly in Gram-negative bacteria.

PMID- 29018095
TI  - A systematic review of interventions to foster physician resilience.
AB  - This review aimed to synthesise the literature describing interventions to
      improve resilience among physicians, to evaluate the quality of this research and
      to outline the type and efficacy of interventions implemented. Searches were
      conducted in April 2017 using five electronic databases. Reference lists of
      included studies and existing review papers were screened. English language, peer
      reviewed studies evaluating interventions to improve physician resilience were
      included. Data were extracted on setting, design, participant and intervention
      characteristics and outcomes. Methodological quality was assessed using the Downs
      and Black checklist. Twenty-two studies were included. Methodological quality was
      low to moderate. The most frequently employed interventional strategies were
      psychosocial skills training and mindfulness training. Effect sizes were
      heterogeneous. Methodologically rigorous research is required to establish best
      practice in improving resilience among physicians and to better consider how
      healthcare settings should be considered within interventions.

PMID- 29018093
TI  - How activating mutations affect MEK1 regulation and function.
AB  - The MEK1 kinase directly phosphorylates ERK2, after the activation loop of MEK1
      is itself phosphorylated by Raf. Studies over the past decade have revealed a
      large number of disease-related mutations in the MEK1 gene that lead to
      tumorigenesis and abnormal development. Several of these mutations result in MEK1
      constitutive activity, but how they affect MEK1 regulation and function remains
      largely unknown. Here, we address these questions focusing on two pathogenic
      variants of the Phe-53 residue, which maps to the well-characterized negative
      regulatory region of MEK1. We found that these variants are phosphorylated by Raf
      faster than the wild-type enzyme, and this phosphorylation further increases
      their enzymatic activity. However, the maximal activities of fully phosphorylated
      wild-type and mutant enzymes are indistinguishable. On the basis of available
      structural information, we propose that the activating substitutions destabilize
      the inactive conformation of MEK1, resulting in its constitutive activity and
      making it more prone to Raf-mediated phosphorylation. Experiments in zebrafish
      revealed that the effects of activating variants on embryonic development reflect
      the joint control of the negative regulatory region and activating
      phosphorylation. Our results underscore the complexity of the effects of
      activating mutations on signaling systems, even at the level of a single protein.

PMID- 29018098
TI  - Toward More Meaningful Accountability to the Public: Assessing Lifelong
      Competence of Physicians.

PMID- 29018097
TI  - Leaf and Plant Age Affects Photosynthetic Performance and Photoprotective
      Capacity.
AB  - In this work, we studied the changes in high-light tolerance and photosynthetic
      activity in leaves of the Arabidopsis (Arabidopsis thaliana) rosette throughout
      the vegetative stage of growth. We implemented an image-analysis work flow to
      analyze the capacity of both the whole plant and individual leaves to cope with
      excess excitation energy by following the changes in absorbed light energy
      partitioning. The data show that leaf and plant age are both important factors
      influencing the fate of excitation energy. During the dark-to-light transition,
      the age of the plant affects mostly steady-state levels of photochemical and
      nonphotochemical quenching, leading to an increased photosynthetic performance of
      its leaves. The age of the leaf affects the induction kinetics of
      nonphotochemical quenching. These observations were confirmed using model
      selection procedures. We further investigated how different leaves on a rosette
      acclimate to high light and show that younger leaves are less prone to
      photoinhibition than older leaves. Our results stress that both plant and leaf
      age should be taken into consideration during the quantification of
      photosynthetic and photoprotective traits to produce repeatable and reliable
      results.

PMID- 29018094
TI  - Substrate-induced conformational changes in the nucleotide-binding domains of
      lipid bilayer-associated P-glycoprotein during ATP hydrolysis.
AB  - P-glycoprotein (Pgp) is an efflux pump important in multidrug resistance of
      cancer cells and in determining drug pharmacokinetics. Pgp is a prototype ATP
      binding cassette transporter with two nucleotide-binding domains (NBDs) that bind
      and hydrolyze ATP. Conformational changes at the NBDs (the Pgp engines) lead to
      changes across Pgp transmembrane domains that result in substrate translocation.
      According to current alternating access models (substrate-binding pocket
      accessible only to one side of the membrane at a time), binding of ATP promotes
      NBD dimerization, resulting in external accessibility of the drug-binding site
      (outward-facing, closed NBD conformation), and ATP hydrolysis leads to
      dissociation of the NBDs with the subsequent return of the accessibility of the
      binding site to the cytoplasmic side (inward-facing, open NBD conformation).
      However, previous work has not investigated these events under near-physiological
      conditions in a lipid bilayer and in the presence of transport substrate. Here,
      we used luminescence resonance energy transfer (LRET) to measure the distances
      between the two Pgp NBDs. Pgp was labeled with LRET probes, reconstituted in
      lipid nanodiscs, and the distance between the NBDs was measured at 37  degrees C.
      In the presence of verapamil, a substrate that activates ATP hydrolysis, the NBDs
      of Pgp reconstituted in nanodiscs were never far apart during the hydrolysis
      cycle, and we never observed the NBD-NBD distances of tens of A that have
      previously been reported. However, we found two main conformations that coexist
      in a dynamic equilibrium under all conditions studied. Our observations highlight
      the importance of performing studies of efflux pumps under near-physiological
      conditions, in a lipid bilayer, at 37  degrees C, and during substrate-stimulated
      hydrolysis.

PMID- 29018096
TI  - The Distinct Roles of Class I and II RPD3-Like Histone Deacetylases in Salinity
      Stress Response.
AB  - Histone acetylation is an essential process in the epigenetic regulation of
      diverse biological processes, including environmental stress responses in plants.
      Previously, our research group identified a histone deacetylase (HDAC) inhibitor
      (HDI) that confers salt tolerance in Arabidopsis (Arabidopsis thaliana). In this
      study, we demonstrate that class I HDAC (HDA19) and class II HDACs
      (HDA5/14/15/18) control responses to salt stress through different pathways. The
      screening of 12 different selective HDIs indicated that seven newly reported HDIs
      enhance salt tolerance. Genetic analysis, based on a pharmacological study,
      identified which HDACs function in salinity stress tolerance. In the wild-type
      Columbia-0 background, hda19 plants exhibit tolerance to high-salinity stress,
      while hda5/14/15/18 plants exhibit hypersensitivity to salt stress. Transcriptome
      analysis revealed that the effect of HDA19 deficiency on the response to salinity
      stress is distinct from that of HDA5/14/15/18 deficiencies. In hda19 plants, the
      expression levels of stress tolerance-related genes, late embryogenesis abundant
      proteins that prevent protein aggregation and positive regulators such as ABI5
      and NAC019 in abscisic acid signaling, were induced strongly relative to the wild
      type. Neither of these elements was up-regulated in the hda5/14/15/18 plants. The
      mutagenesis of HDA19 by genome editing in the hda5/14/15/18 plants enhanced salt
      tolerance, suggesting that suppression of HDA19 masks the phenotype caused by the
      suppression of class II HDACs in the salinity stress response. Collectively, our
      results demonstrate that HDIs that inhibit class I HDACs allow the rescue of
      plants from salinity stress regardless of their selectivity, and they provide
      insight into the hierarchal regulation of environmental stress responses through
      HDAC isoforms.

PMID- 29018099
TI  - Feedback Control in Hemodialysis-Much Ado about Nothing?

PMID- 29018101
TI  - Maintenance of Certification: Framing the Dialogue.

PMID- 29018103
TI  - Maintenance of Certification: Demonstrating Ongoing Competence.

PMID- 29018102
TI  - Transformation of ABIM and What the Changes Mean to Nephrologists.

PMID- 29018104
TI  - Much Activity, Uncertainty Remains.
AB  - Bipartisan market stabilization negotiations gave way to a last-gasp attempt at
      repeal and replace; the ACA emerged intact but buffeted by uncertainty.

PMID- 29018106
TI  - Second-trimester abortion: women often lack the choice they should be offered.

PMID- 29018100
TI  - Randomized Crossover Trial of Blood Volume Monitoring-Guided Ultrafiltration
      Biofeedback to Reduce Intradialytic Hypotensive Episodes with Hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: Intradialytic hypotension (IDH) is associated with
      morbidity. The effect of blood volume-guided ultrafiltration biofeedback, which
      automatically adjusts fluid removal rate on the basis of blood volume parameters,
      on the reduction of IDH was tested in a randomized crossover trial. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a 22-week, single blind,
      randomized crossover trial in patients receiving maintenance hemodialysis who had
      >30% of sessions complicated by symptomatic IDH in five centers in Calgary,
      Alberta, Canada. Participants underwent a 4-week run-in period to standardize
      dialysis prescription and dry weight on the basis of clinical examination. Those
      meeting inclusion criteria were randomized to best clinical practice hemodialysis
      (control) or best clinical practice plus blood volume-guided ultrafiltration
      biofeedback (intervention) for 8 weeks, followed by a 2-week washout and
      subsequent crossover for a second 8-week phase. The primary outcome was rate of
      symptomatic IDH. RESULTS: Thirty-five participants entered, 32 were randomized,
      and 26 completed the study. The rate of symptomatic IDH with biofeedback was
      0.10/h (95% confidence interval, 0.06 to 0.14) and 0.07/h (95% confidence
      interval, 0.05 to 0.10) during control (P=0.29). There were no differences in the
      rate or proportion of sessions with asymptomatic IDH or symptoms alone. Results
      remained consistent when adjusted for randomization order and study week. There
      were no differences between intervention and control in the last study week in
      interdialytic weight gain (difference [SD], -0.02 [0.8] kg), brain natriuretic
      peptide (1460 [19,052] ng/L), cardiac troponins (3 [86] ng/L), extracellular
      water-to-intracellular water ratio (0.05 [0.33]), ultrafiltration rate (1.1 [7.0]
      ml/kg per hour), and dialysis recovery time (0.43 [19.25] hours). CONCLUSION: The
      use of blood volume monitoring-guided ultrafiltration biofeedback in patients
      prone to IDH did not reduce the rate of symptomatic IDH events.

PMID- 29018107
TI  - Incentivising contraceptive use: a helping hand or a push in the wrong direction?

PMID- 29018108
TI  - Communication blocks and the power of rethinking.

PMID- 29018109
TI  - Resources for service provision: policies and politics.

PMID- 29018110
TI  - Authors' response to 'Comment on 'Effects of injectable progestogen contraception
      versus the copper intrauterine device on HIV acquisition: sub-study of a
      pragmatic randomised controlled trial' '.

PMID- 29018111
TI  - Correction: 'Mind the gap: responding to the global funding crisis in family
      planning'.

PMID- 29018113
TI  - Venus.

PMID- 29018112
TI  - Correction: 'Expanding family planning options: offering the Standard Days
      MethodTM to women in Istanbul'.

PMID- 29018114
TI  - Removal of Mirena(r) with fibrous tissue around the arms.

PMID- 29018115
TI  - Kaposi's Sarcoma-Associated Herpesvirus Increases PD-L1 and Proinflammatory
      Cytokine Expression in Human Monocytes.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with the human
      malignancy Kaposi's sarcoma and the lymphoproliferative disorders primary
      effusion lymphoma and multicentric Castleman's disease. KSHV establishes lytic
      infection of monocytes in vivo, which may represent an important cellular
      reservoir during KS disease progression. KS tumors consist of latently infected
      endothelial cells; however, lytic phase gene products are important for KS onset.
      Early KS lesion progression is driven by proinflammatory cytokines supplied by
      immune cell infiltrates including T cells and monocytes. KSHV-infected monocytes
      may supply the lytic viral products and the inflammatory milieu conducive to KS
      tumor progression. To establish successful infection, KSHV extensively modulates
      the host immune system. KSHV antigens activate both innate and adaptive immune
      responses including KSHV-specific T cells, but lifelong infection is still
      established. Programmed death ligand 1 (PD-L1) is a prosurvival cell surface
      protein that suppresses T-cell-mediated killing. PD-L1 is variably present on
      various tumor cells and is a targetable marker for cancer treatment. We show that
      KSHV infection of human monocytes increases PD-L1 expression and transcription in
      a dose-dependent manner. We also saw evidence of lytic gene expression in the
      KSHV-infected monocytes. Intact KSHV is needed for full PD-L1 response in human
      monocytes. KSHV induces a general proinflammatory cytokine milieu including
      interleukins 1alpha, 1beta, and 6, which have been implicated in early KS lesion
      progression. KSHV-mediated PD-L1 increase may represent a novel mechanism of KSHV
      mediated immune modulation to allow for virus survival and eventually malignant
      progression.IMPORTANCE KSHV is the etiologic agent of Kaposi's sarcoma and the
      lymphoproliferative disorders primary effusion lymphoma and multicentric
      Castleman's disease. Programmed death ligand 1 (PD-L1) is an immunosuppressive
      cell surface marker that inhibits T cell activation. We report that KSHV
      infection of primary human monocytes upregulates PD-L1 transcription and protein
      expression. Analysis of the cytokine and chemokine milieu following KSHV
      infection of monocytes revealed that KSHV induces interleukins 1alpha, 1beta, and
      6, all of which have been implicated in KS development. Our work has identified
      another potential immune evasion strategy for KSHV and a potential target for
      immunotherapy of KSHV-derived disease.

PMID- 29018116
TI  - Quinolone Resistance Reversion by Targeting the SOS Response.
AB  - Suppression of the SOS response has been postulated as a therapeutic strategy for
      potentiating antimicrobial agents. We aimed to evaluate the impact of its
      suppression on reversing resistance using a model of isogenic strains of
      Escherichia coli representing multiple levels of quinolone resistance. E. coli
      mutants exhibiting a spectrum of SOS activity were constructed from isogenic
      strains carrying quinolone resistance mechanisms with susceptible and resistant
      phenotypes. Changes in susceptibility were evaluated by static (MICs) and dynamic
      (killing curves or flow cytometry) methodologies. A peritoneal sepsis murine
      model was used to evaluate in vivo impact. Suppression of the SOS response was
      capable of resensitizing mutant strains with genes encoding three or four
      different resistance mechanisms (up to 15-fold reductions in MICs). Killing curve
      assays showed a clear disadvantage for survival (Deltalog10 CFU per milliliter
      [CFU/ml] of 8 log units after 24 h), and the in vivo efficacy of ciprofloxacin
      was significantly enhanced (Deltalog10 CFU/g of 1.76 log units) in resistant
      strains with a suppressed SOS response. This effect was evident even after short
      periods (60 min) of exposure. Suppression of the SOS response reverses
      antimicrobial resistance across a range of E. coli phenotypes from reduced
      susceptibility to highly resistant, playing a significant role in increasing the
      in vivo efficacy.IMPORTANCE The rapid rise of antibiotic resistance in bacterial
      pathogens is now considered a major global health crisis. New strategies are
      needed to block the development of resistance and to extend the life of
      antibiotics. The SOS response is a promising target for developing therapeutics
      to reduce the acquisition of antibiotic resistance and enhance the bactericidal
      activity of antimicrobial agents such as quinolones. Significant questions remain
      regarding its impact as a strategy for the reversion or resensitization of
      antibiotic-resistant bacteria. To address this question, we have generated E.
      coli mutants that exhibited a spectrum of SOS activity, ranging from a natural
      SOS response to a hypoinducible or constitutively suppressed response. We tested
      the effects of these mutations on quinolone resistance reversion under
      therapeutic concentrations in a set of isogenic strains carrying different
      combinations of chromosome- and plasmid-mediated quinolone resistance mechanisms
      with susceptible, low-level quinolone resistant, resistant, and highly resistant
      phenotypes. Our comprehensive analysis opens up a new strategy for reversing drug
      resistance by targeting the SOS response.

PMID- 29018117
TI  - Reciprocal Prioritization to Dietary Glycans by Gut Bacteria in a Competitive
      Environment Promotes Stable Coexistence.
AB  - When presented with nutrient mixtures, several human gut Bacteroides species
      exhibit hierarchical utilization of glycans through a phenomenon that resembles
      catabolite repression. However, it is unclear how closely these observed
      physiological changes, often measured by altered transcription of glycan
      utilization genes, mirror actual glycan depletion. To understand the glycan
      prioritization strategies of two closely related human gut symbionts, Bacteroides
      ovatus and Bacteroides thetaiotaomicron, we performed a series of time course
      assays in which both species were individually grown in a medium with six
      different glycans that both species can degrade. Disappearance of the substrates
      and transcription of the corresponding polysaccharide utilization loci (PULs)
      were measured. Each species utilized some glycans before others, but with
      different priorities per species, providing insight into species-specific
      hierarchical preferences. In general, the presence of highly prioritized glycans
      repressed transcription of genes involved in utilizing lower-priority nutrients.
      However, transcriptional sensitivity to some glycans varied relative to the
      residual concentration in the medium, with some PULs that target high-priority
      substrates remaining highly expressed even after their target glycan had been
      mostly depleted. Coculturing of these organisms in the same mixture showed that
      the hierarchical orders generally remained the same, promoting stable
      coexistence. Polymer length was found to be a contributing factor for glycan
      utilization, thereby affecting its place in the hierarchy. Our findings not only
      elucidate how B. ovatus and B. thetaiotaomicron strategically access glycans to
      maintain coexistence but also support the prioritization of carbohydrate
      utilization based on carbohydrate structure, advancing our understanding of the
      relationships between diet and the gut microbiome.IMPORTANCE The microorganisms
      that reside in the human colon fulfill their energy requirements mainly from diet
      and host-derived complex carbohydrates. Members of this ecosystem possess poorly
      understood strategies to prioritize and compete for these nutrients. Based on
      direct carbohydrate measurements and corresponding transcriptional analyses, our
      findings showed that individual bacterial species exhibit different preferences
      for the same set of glycans and that this prioritization is maintained in a
      competitive environment, which may promote stable coexistence. Such understanding
      of gut bacterial glycan utilization will be essential to eliciting predictable
      changes in the gut microbiota to improve health through the diet.

PMID- 29018118
TI  - Transgenerational Diapause as an Avoidance Strategy against Bacterial Pathogens
      in Caenorhabditis elegans.
AB  - The dynamic response of organisms exposed to environmental pathogens determines
      their survival or demise, and the outcome of this interaction depends on the
      host's susceptibility and pathogen-dependent virulence factors. The transmission
      of acquired information about the nature of a pathogen to progeny may ensure
      effective defensive strategies for the progeny's survival in adverse
      environments. Environmental RNA interference (RNAi) is a systemic and heritable
      mechanism and has recently been linked to antibacterial and antifungal defenses
      in both plants and animals. Here, we report that the second generation of
      Caenorhabditis elegans living on pathogenic bacteria can avoid bacterial
      infection by entering diapause in an RNAi pathway-dependent mechanism.
      Furthermore, we demonstrate that the information encoding this survival strategy
      is transgenerationally transmitted to the progeny via the maternal germ
      line.IMPORTANCE Bacteria vastly influence physiology and behavior, and yet, the
      specific mechanisms by which they cause behavioral changes in hosts are not
      known. We use C. elegans as a host and the bacteria they eat to understand how
      microbes trigger a behavioral change that helps animals to survive. We found that
      animals faced with an infection for two generations could enter a hibernationlike
      state, arresting development by forming dauer larvae. Dauers have closed mouths
      and effectively avoid infection. Animals accumulate information that is
      transgenerationally transmitted to the next generations to form dauers. This work
      gives insight on how bacteria communicate in noncanonical ways with their hosts,
      resulting in long-lasting effects providing survival strategies to the community.

PMID- 29018119
TI  - Globally Important Haptophyte Algae Use Exogenous Pyrimidine Compounds More
      Efficiently than Thiamin.
AB  - Vitamin B1 (thiamin) is a cofactor for critical enzymatic processes and is scarce
      in surface oceans. Several eukaryotic marine algal species thought to rely on
      exogenous thiamin are now known to grow equally well on the precursor 4-amino-5
      hydroxymethyl-2-methylpyrimidine (HMP), including the haptophyte Emiliania
      huxleyi Because the thiamin biosynthetic capacities of the diverse and
      ecologically important haptophyte lineage are otherwise unknown, we investigated
      the pathway in transcriptomes and two genomes from 30 species representing six
      taxonomic orders. HMP synthase is missing in data from all studied taxa, but the
      pathway is otherwise complete, with some enzymatic variations. Experiments on
      axenic species from three orders demonstrated that equivalent growth rates were
      supported by 1 uM HMP or thiamin amendment. Cellular thiamin quotas were
      quantified in the oceanic phytoplankter E. huxleyi using the thiochrome assay. E.
      huxleyi exhibited luxury storage in standard algal medium [(1.16 +/- 0.18) * 10-6
      pmol thiamin cell-1], whereas quotas in cultures grown under more environmentally
      relevant thiamin and HMP supplies [(2.22 +/- 0.07) * 10-7 or (1.58 +/- 0.14) * 10
      7 pmol thiamin cell-1, respectively] were significantly lower than luxury values
      and prior estimates. HMP and its salvage-related analog 4-amino-5-aminomethyl-2
      methylpyrimidine (AmMP) supported higher growth than thiamin under
      environmentally relevant supply levels. These compounds also sustained growth of
      the stramenopile alga Pelagomonas calceolata Together with identification of a
      salvage protein subfamily (TENA_E) in multiple phytoplankton, the results
      indicate that salvaged AmMP and exogenously acquired HMP are used by several
      groups for thiamin production. Our studies highlight the potential importance of
      thiamin pathway intermediates and their analogs in shaping phytoplankton
      community structure.IMPORTANCE The concept that vitamin B1 (thiamin) availability
      in seawater controls the productivity and structure of eukaryotic phytoplankton
      communities has been discussed for half a century. We examined B1 biosynthesis
      and salvage pathways in diverse phytoplankton species. These comparative genomic
      analyses as well as experiments show that phytoplankton thought to require
      exogenous B1 not only utilize intermediate compounds to meet this need but also
      exhibit stronger growth on these compounds than on thiamin. Furthermore, oceanic
      phytoplankton have lower cellular thiamin quotas than previously reported, and
      salvage of intermediate compounds is likely a key mechanism for meeting B1
      requirements under environmentally relevant scenarios. Thus, several lines of
      evidence now suggest that availability of specific precursor molecules could be
      more important in structuring phytoplankton communities than the vitamin itself.
      This understanding of preferential compound utilization and thiamin quotas will
      improve biogeochemical model parameterization and highlights interaction networks
      among ocean microbes.

PMID- 29018120
TI  - An Engineered Synthetic Pathway for Discovering Nonnatural Nonribosomal Peptides
      in Escherichia coli.
AB  - Peptides that are synthesized independently of the ribosome in plants, fungi, and
      bacteria can have clinically relevant anticancer, antihemochromatosis, and
      antiviral activities, among many other. Despite their natural origin, discovering
      new natural products is challenging, and there is a need to expand the chemical
      diversity that is accessible. In this work, we created a novel, compressed
      synthetic pathway for the heterologous expression and diversification of
      nonribosomal peptides (NRPs) based on homologs of siderophore pathways from
      Escherichia coli and Vibrio cholerae To enhance the likelihood of successful
      molecule production, we established a selective pressure via the iron-chelating
      properties of siderophores. By supplementing cells containing our synthetic
      pathway with different precursors that are incorporated into the pathway
      independently of NRP enzymes, we generated over 20 predesigned, novel, and
      structurally diverse NRPs. This engineering approach, where phylogenetically
      related genes from different organisms are integrated and supplemented with novel
      precursors, should enable heterologous expression and molecular diversification
      of NRPs.IMPORTANCE Nonribosomal peptides (NRPs) constitute a source of bioactive
      molecules with potential therapeutic applications. However, discovering novel
      NRPs by rational engineering of biosynthetic pathways remains challenging. Here,
      we show that a synthetic compressed pathway in which we replaced biosynthetic
      genes with their ancestral homologs and orthologs enabled successful heterologous
      NRP expression. Polyamines added exogenously were incorporated into nascent NRPs,
      and molecular production was pressured by growing the host under conditions that
      make such NRPs beneficial for survival. This multilayered approach resulted in
      the assembly of over 20 distinct and novel molecules. We envision this strategy
      being used to enable the production of NRPs from heterologous pathways.

PMID- 29018121
TI  - Dysbiosis and Its Discontents.
AB  - Dysbiosis is a key term in human microbiome research, especially when microbiome
      patterns are associated with disease states. Although some questions have been
      raised about how this term is applied, its use continues undiminished in the
      literature. We investigate the ways in which microbiome researchers discuss
      dysbiosis and then assess the impact of different concepts of dysbiosis on
      microbiome research. After an overview of the term's historical roots, we conduct
      quantitative and qualitative analyses of a large selection of contemporary
      dysbiosis statements. We categorize both short definitions and longer conceptual
      statements about dysbiosis. Further analysis allows us to identify the
      problematic implications of how dysbiosis is used, particularly with regard to
      causal hypotheses and normal-abnormal distinctions. We suggest that researchers
      should reflect carefully on the ways in which they discuss dysbiosis, in order
      for the field to continue to develop greater predictive scope and explanatory
      depth.

PMID- 29018124
TI  - Straight from the Horse's "Mouth": Genomic Epidemiology of an Icelandic Equine
      Epidemic.
AB  - Despite tight biosecurity measures, an outbreak of respiratory disease rapidly
      spread across the Icelandic equine population in 2010. Horse transportation was
      brought to a halt in order to contain the spread of the infectious agent. In a
      recent article, Bjornsdottir and colleagues (S. Bjornsdottir et al., mBio
      8:e00826-17, 2017, https://doi.org/10.1128/mBio.00826-17) employ the power and
      resolution of "genomic epidemiology," the combination of whole genomic sequencing
      and epidemiological approaches, to examine the source and spread of the outbreak.
      Intriguingly, the outbreak was not viral in origin, but linked to a bacterial
      "commensal" Streptococcus equi subsp. zooepidemicus infection. A national
      sampling strategy coupled with population genomics revealed that the outbreak was
      most likely driven by a S. equi subsp. zooepidemicus sequence type 209 (ST209)
      infection that spread nationally from a single source. This retrospective study
      demonstrates the power of genomics applied on a national scale to unravel the
      cause of a significant biosecurity threat.

PMID- 29018122
TI  - The BvgAS Regulon of Bordetella pertussis.
AB  - Nearly all virulence factors in Bordetella pertussis are activated by a master
      two-component system, BvgAS, composed of the sensor kinase BvgS and the response
      regulator BvgA. When BvgS is active, BvgA is phosphorylated (BvgA~P), and
      virulence-activated genes (vags) are expressed [Bvg(+) mode]. When BvgS is
      inactive and BvgA is not phosphorylated, virulence-repressed genes (vrgs) are
      induced [Bvg(-) mode]. Here, we have used transcriptome sequencing (RNA-seq) and
      reverse transcription-quantitative PCR (RT-qPCR) to define the BvgAS-dependent
      regulon of B. pertussis Tohama I. Our analyses reveal more than 550 BvgA
      regulated genes, of which 353 are newly identified. BvgA-activated genes include
      those encoding two-component systems (such as kdpED), multiple other
      transcriptional regulators, and the extracytoplasmic function (ECF) sigma factor
      brpL, which is needed for type 3 secretion system (T3SS) expression, further
      establishing the importance of BvgA~P as an apex regulator of transcriptional
      networks promoting virulence. Using in vitro transcription, we demonstrate that
      the promoter for brpL is directly activated by BvgA~P. BvgA-FeBABE cleavage
      reactions identify BvgA~P binding sites centered at positions -41.5 and -63.5 in
      bprL Most importantly, we show for the first time that genes for multiple and
      varied metabolic pathways are significantly upregulated in the B. pertussis Bvg(
      ) mode. These include genes for fatty acid and lipid metabolism, sugar and amino
      acid transporters, pyruvate dehydrogenase, phenylacetic acid degradation, and the
      glycolate/glyoxylate utilization pathway. Our results suggest that metabolic
      changes in the Bvg(-) mode may be participating in bacterial survival,
      transmission, and/or persistence and identify over 200 new vrgs that can be
      tested for function.IMPORTANCE Within the past 20 years, outbreaks of whooping
      cough, caused by Bordetella pertussis, have led to respiratory disease and infant
      mortalities, despite good vaccination coverage. This is due, at least in part, to
      the introduction of a less effective acellular vaccine in the 1990s. It is
      crucial, then, to understand the molecular basis of B. pertussis growth and
      infection. The two-component system BvgA (response regulator)/BvgS (histidine
      kinase) is the master regulator of B. pertussis virulence genes. We report here
      the first RNA-seq analysis of the BvgAS regulon in B. pertussis, revealing that
      more than 550 genes are regulated by BvgAS. We show that genes for multiple and
      varied metabolic pathways are highly regulated in the Bvg(-) mode (absence of
      BvgA phosphorylation). Our results suggest that metabolic changes in the Bvg(-)
      mode may be participating in bacterial survival, transmission, and/or
      persistence.

PMID- 29018123
TI  - Characterization of Inner and Outer Membrane Proteins from Francisella tularensis
      Strains LVS and Schu S4 and Identification of Potential Subunit Vaccine
      Candidates.
AB  - Francisella tularensis is the causative agent of tularemia and a potential
      bioterrorism agent. In the present study, we isolated, identified, and quantified
      the proteins present in the membranes of the virulent type A strain, Schu S4, and
      the attenuated type B strain, LVS (live vaccine strain). Spectral counting of
      mass spectrometric data showed enrichment for membrane proteins in both strains.
      Mice vaccinated with whole LVS membranes encapsulated in poly (lactic-co-glycolic
      acid) (PLGA) nanoparticles containing the adjuvant polyinosinic-polycytidylic
      acid [poly(I.C)] showed significant protection against a challenge with LVS
      compared to the results seen with naive mice or mice vaccinated with either
      membranes or poly(I.C) alone. The PLGA-encapsulated Schu S4 membranes with
      poly(I.C) alone did not significantly protect mice from a lethal intraperitoneal
      challenge with Schu S4; however, this vaccination strategy provided protection
      from LVS challenge. Mice that received the encapsulated Schu S4 membranes
      followed by a booster of LVS bacteria showed significant protection with respect
      to a lethal Schu S4 challenge compared to control mice. Western blot analyses of
      the sera from the Schu S4-vaccinated mice that received an LVS booster showed
      four immunoreactive bands. One of these bands from the corresponding one
      dimensional (1D) SDS-PAGE experiment represented capsule. The remaining bands
      were excised, digested with trypsin, and analyzed using mass spectrometry. The
      most abundant proteins present in these immunoreactive samples were an outer
      membrane OmpA-like protein, FopA; the type IV pilus fiber building block protein;
      a hypothetical membrane protein; and lipoproteins LpnA and Lpp3. These proteins
      should serve as potential targets for future recombinant protein vaccination
      studies.IMPORTANCE The low infectious dose, the high potential
      mortality/morbidity rates, and the ability to be disseminated as an aerosol make
      Francisella tularensis a potential agent for bioterrorism. These characteristics
      led the Centers for Disease Control (CDC) to classify F. tularensis as a Tier 1
      pathogen. Currently, there is no vaccine approved for general use in the United
      States.

PMID- 29018125
TI  - More than Enzymes That Make or Break Cyclic Di-GMP-Local Signaling in the
      Interactome of GGDEF/EAL Domain Proteins of Escherichia coli.
AB  - The bacterial second messenger bis-(3'-5')-cyclic diguanosine monophosphate (c-di
      GMP) ubiquitously promotes bacterial biofilm formation. Intracellular pools of c
      di-GMP seem to be dynamically negotiated by diguanylate cyclases (DGCs, with
      GGDEF domains) and specific phosphodiesterases (PDEs, with EAL or HD-GYP
      domains). Most bacterial species possess multiple DGCs and PDEs, often with
      surprisingly distinct and specific output functions. One explanation for such
      specificity is "local" c-di-GMP signaling, which is believed to involve direct
      interactions between specific DGC/PDE pairs and c-di-GMP-binding effector/target
      systems. Here we present a systematic analysis of direct protein interactions
      among all 29 GGDEF/EAL domain proteins of Escherichia coli Since the effects of
      interactions depend on coexpression and stoichiometries, cellular levels of all
      GGDEF/EAL domain proteins were also quantified and found to vary dynamically
      along the growth cycle. Instead of detecting specific pairs of interacting DGCs
      and PDEs, we discovered a tightly interconnected protein network of a specific
      subset or "supermodule" of DGCs and PDEs with a coregulated core of five
      hyperconnected hub proteins. These include the DGC/PDE proteins representing the
      c-di-GMP switch that turns on biofilm matrix production in E. coli Mutants
      lacking these core hub proteins show drastic biofilm-related phenotypes but no
      changes in cellular c-di-GMP levels. Overall, our results provide the basis for a
      novel model of local c-di-GMP signaling in which a single strongly expressed
      master PDE, PdeH, dynamically eradicates global effects of several DGCs by
      strongly draining the global c-di-GMP pool and thereby restricting these DGCs to
      serving as local c-di-GMP sources that activate specific colocalized
      effector/target systems.IMPORTANCE c-di-GMP signaling in bacteria is believed to
      occur via changes in cellular c-di-GMP levels controlled by antagonistic and
      potentially interacting pairs of diguanylate cyclases (DGCs) and c-di-GMP
      phosphodiesterases (PDEs). Our systematic analysis of protein-protein interaction
      patterns of all 29 GGDEF/EAL domain proteins of E. coli, together with our
      measurements of cellular c-di-GMP levels, challenges both aspects of this current
      concept. Knocking out distinct DGCs and PDEs has drastic effects on E. coli
      biofilm formation without changing the cellular c-di-GMP level. In addition,
      rather than generally coming in interacting DGC/PDE pairs, a subset of DGCs and
      PDEs operates as central interaction hubs in a larger "supermodule," with other
      DGCs and PDEs behaving as "lonely players" without contacts to other c-di-GMP
      related enzymes. On the basis of these data, we propose a novel concept of
      "local" c-di-GMP signaling in bacteria with multiple enzymes that make or break
      the second messenger c-di-GMP.

PMID- 29018128
TI  - Island Sign: An Imaging Predictor for Early Hematoma Expansion and Poor Outcome
      in Patients With Intracerebral Hemorrhage.
AB  - BACKGROUND AND PURPOSE: The aim of the study was to investigate the usefulness of
      the computed tomography (CT) island sign for predicting early hematoma growth and
      poor functional outcome. METHODS: We included patients with spontaneous
      intracerebral hemorrhage (ICH) who had undergone baseline CT within 6 hours after
      ICH symptom onset in our hospital between July 2011 and September 2016. Two
      readers independently assessed the presence of the island sign on the admission
      noncontrast CT scan. Multivariable logistic regression analysis was used to
      analyze the association between the presence of the island sign on noncontrast
      admission CT and early hematoma growth and functional outcome. RESULTS: A total
      of 252 patients who met the inclusion criteria were analyzed. Among them, 41
      (16.3%) patients had the island sign on baseline noncontrast CT scans. In
      addition, the island sign was observed in 38 of 85 patients (44.7%) with hematoma
      growth. Multivariate logistic regression analysis demonstrated that the time to
      baseline CT scan, initial hematoma volume, and the presence of the island sign on
      baseline CT scan independently predicted early hematoma growth. The sensitivity
      of the island sign for predicting hematoma expansion was 44.7%, specificity
      98.2%, positive predictive value 92.7%, and negative predictive value 77.7%.
      After adjusting for the patients' age, baseline Glasgow Coma Scale score,
      presence of intraventricular hemorrhage, presence of subarachnoid hemorrhage,
      admission systolic blood pressure, baseline ICH volume, and infratentorial
      location, the presence of the island sign (odds ratio, 3.51; 95% confidence
      interval, 1.26-9.81; P=0.017) remained an independent predictor of poor outcome
      in patients with ICH. CONCLUSIONS: The island sign is a reliable CT imaging
      marker that independently predicts hematoma expansion and poor outcome in
      patients with ICH. The noncontrast CT island sign may serve as a potential marker
      for therapeutic intervention.

PMID- 29018126
TI  - Systematic Identification of Mycobacterium tuberculosis Effectors Reveals that
      BfrB Suppresses Innate Immunity.
AB  - Mycobacterium tuberculosis (Mtb) has evolved multiple strategies to counter the
      human immune system. The effectors of Mtb play important roles in the
      interactions with the host. However, because of the lack of highly efficient
      strategies, there are only a handful of known Mtb effectors, thus hampering our
      understanding of Mtb pathogenesis. In this study, we probed Mtb proteome
      microarray with biotinylated whole-cell lysates of human macrophages, identifying
      26 Mtb membrane proteins and secreted proteins that bind to macrophage proteins.
      Combining GST pull-down with mass spectroscopy then enabled the specific
      identification of all binders. We refer to this proteome microarray-based
      strategy as SOPHIE (Systematic unlOcking of Pathogen and Host Interacting
      Effectors). Detailed investigation of a novel effector identified here, the iron
      storage protein BfrB (Rv3841), revealed that BfrB inhibits NF-kappaB-dependent
      transcription through binding and reducing the nuclear abundance of the ribosomal
      protein S3 (RPS3), which is a functional subunit of NF- kappaB. The importance of
      this interaction was evidenced by the promotion of survival in macrophages of the
      mycobacteria, Mycobacterium smegmatis, by overexpression of BfrB. Thus, beyond
      demonstrating the power of SOPHIE in the discovery of novel effectors of human
      pathogens, we expect that the set of Mtb effectors identified in this work will
      greatly facilitate the understanding of the pathogenesis of Mtb, possibly leading
      to additional potential molecular targets in the battle against tuberculosis.

PMID- 29018127
TI  - Bosutinib Attenuates Inflammation via Inhibiting Salt-Inducible Kinases in
      Experimental Model of Intracerebral Hemorrhage on Mice.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a subtype of stroke
      with highest mortality and morbidity. Pronounced inflammation plays a significant
      role in the development of the secondary brain injury after ICH. Recently, SIK-2
      (salt-inducible kinase-2) was identified as an important component controlling
      inflammatory response. Here we sought to investigate the role of SIK-2 in post
      ICH inflammation and potential protective effects of SIK-2 inhibition after ICH.
      METHODS: Two hundred and ninety-three male CD-1 mice were used. ICH was induced
      via injection of 30 MUL of autologous blood. Recombinant SIK-2 was administrated
      1 hour after ICH intracerebroventricularly. SIK-2 small interfering RNA was
      injected intracerebroventricularly 24 hours before ICH. Bosutinib, a clinically
      approved tyrosine kinase inhibitor with affinity to SIK-2, was given intranasally
      1 hour or 6 hours after ICH. Effects of treatments were evaluated by neurological
      tests and brain water content calculation. Molecular pathways were investigated
      by Western blots and immunofluorescence studies. RESULTS: Endogenous SIK-2 was
      expressed in microglia and neurons. SIK-2 expression was reduced after ICH.
      Exogenous SIK-2 aggravated post-ICH inflammation, leading to brain edema and the
      neurobehavioral deficits. SIK-2 inhibition attenuated post-ICH inflammation,
      reducing brain edema and ameliorating neurological dysfunctions. Bosutinib
      inhibited SIK-2-attenuating ICH-induced brain damage. Protective effects of
      Bosutinib were mediated, at least partly, by CRTC3 (cyclic amp-response element
      binding protein-regulated transcription coactivator 3)/cyclic amp-response
      element binding protein/NF-kappaB (nuclear factor-kappaB) pathway. CONCLUSIONS:
      SIK-2 participates in inflammation induction after ICH. SIK-2 inhibition via
      Bosutinib or small interfering RNA decreased inflammation, attenuating brain
      injury. SIK-2 effects are, at least partly, mediated by CRTC3-cyclic amp-response
      element binding protein-NF-kappaB signaling pathway.

PMID- 29018130
TI  - Mechanical Thrombectomy in Perioperative Strokes: A Case-Control Study.
AB  - BACKGROUND AND PURPOSE: Perioperative strokes (POS) are rare but serious
      complications for which mechanical thrombectomy could be beneficial. We aimed to
      compare the technical results and patients outcomes in a population of POS versus
      non-POS (nPOS) treated by mechanical thrombectomy. METHODS: From 2010 to 2017, 25
      patients with POS (ie, acute ischemic stroke occurring during or within 30 days
      after a procedure) who underwent mechanical thrombectomy (POS group) were
      enrolled and paired with 50 consecutive patients with nPOS (control group), based
      on the occlusion's site, National Institute of Health Stroke Scale, and age.
      RESULTS: Respectively, mean age was 68.3+/-16.6 versus 67.2+/-16.6 years
      (P=0.70), and median National Institute of Health Stroke Scale score at admission
      was 20 (interquartile range, 15-25) versus 19 (interquartile range, 17-25;
      P=0.79). Good clinical outcome (modified Rankin Scale score of 0-2 at 3 months)
      was achieved by 33.3% (POS) versus 56.5% (nPOS) of patients (P=0.055). Successful
      reperfusion (modified Thrombolysis In Cerebral Infarction score of >=2b) was
      obtained in 76% (POS) versus 86% (nPOS) of cases (P=0.22). Mortality at 3 months
      was 33.3% in the POS group versus 4.2% (nPOS) (P=0.002). The rate of major
      procedural complications was 4% (POS) versus 6% (nPOS); none were lethal. Average
      time from symptoms' onset to reperfusion was 4.9 hours (+/-2.0) in POS versus 5.2
      hours (+/-2.6). CONCLUSIONS: Successful reperfusion seems accessible in POS
      within a reasonable amount of time and with a good level of safety. However,
      favorable outcome was achieved with a lower rate than in nPOS, owing to a higher
      mortality rate.

PMID- 29018129
TI  - Neuroimaging Correlates of Cerebral Microbleeds: The ARIC Study (Atherosclerosis
      Risk in Communities).
AB  - BACKGROUND AND PURPOSE: Cerebral microbleed (CMB) location (deep versus strictly
      lobar) may elucidate underlying pathology with deep CMBs being more associated
      with hypertensive vascular disease and lobar CMBs being more associated with
      cerebral amyloid angiopathy. The objective of this study was to determine whether
      neuroimaging signs of vascular disease and Alzheimer pathology are associated
      with different types of CMBs. METHODS: Among 1677 nondemented ARIC
      (Atherosclerosis Risk in Communities) participants (mean age=76+/-5 years; 40%
      men; 26% black) with 3-Tesla MRI scans at the fifth examination (2011-2013), we
      fit multinomial logistic regression models to quantify relationships of brain
      volumes (Alzheimer disease signature regions, total gray matter, frontal gray
      matter, and white matter hyperintensity volumes), infarct frequencies (lacunar,
      nonlacunar, and total), and apolipoprotein E (number of epsilon4 alleles) with
      CMB location (none, deep/mixed, or strictly lobar CMBs). Models were weighted for
      the sample selection scheme and adjusted for age, sex, education, hypertension,
      ever smoking status, diabetes mellitus, race site membership, and estimated
      intracranial volume (brain volume models only). RESULTS: Deep/mixed and strictly
      lobar CMBs had prevalences of 8% and 16%, respectively. Larger white matter
      hyperintensity burden, greater total infarct frequency, smaller frontal volumes
      (in women only), and smaller total gray matter volume were associated with
      greater risk of both deep and lobar CMBs relative to no CMBs. Greater white
      matter hyperintensity volume was also associated with greater risk of deep
      relative to lobar CMBs. Higher lacunar and nonlacunar infarct frequencies were
      associated with higher risk of deep CMBs, whereas smaller Alzheimer disease
      signature region volume and apolipoprotein E epsilon4 homozygosity were
      associated with greater risk of lobar CMBs. CONCLUSIONS: CMBs are a common
      vascular pathology in the elderly. Markers of hypertensive small-vessel disease
      may contribute to deep CMBs while cerebral amyloid angiopathy may drive
      development of lobar CMBs.

PMID- 29018131
TI  - Incorporating Nonphysician Stroke Specialists Into the Stroke Team.

PMID- 29018133
TI  - Carotid Web (Intimal Fibromuscular Dysplasia) Has High Stroke Recurrence Risk and
      Is Amenable to Stenting.
AB  - BACKGROUND AND PURPOSE: Carotid webs have been increasingly recognized as a cause
      of recurrent stroke, but evidence remains scarce. We aim to report the clinical
      outcomes and first series of carotid stenting in a cohort of patients with
      strokes from symptomatic carotid webs. METHODS: Prospective and consecutive data
      of patients <65 years old with cryptogenic stroke admitted within September 2014
      to May 2017. Carotid web was defined by a shelf-like/linear filling defect in the
      posterior internal carotid artery bulb by computed tomographic angiography.
      RESULTS: Twenty-four patients were identified (91.6% strokes/8.4% transient
      ischemic attacks [TIAs]). Median age was 46 (41-59) years, 61% were female, and
      75% were black. Median National Institutes of Health Stroke Scale score was 10.5
      (3.0-16.0) and ASPECTS (Alberta Stroke Program Early CT Score) was 8 (7-8). There
      were no parenchymal hemorrhages, and 96% of patients were independent at 3
      months. All webs caused <50% stenosis. In patients with bilateral webs (58%),
      median ipsilateral web length was larger than contralateral (3.1 [3.0-4.5] mm
      versus 2.6 [1.85-2.9] mm; P=0.01), respectively. Twenty-nine percent of patients
      had thrombus superimposed on the symptomatic carotid web. A recurrent stroke/TIA
      involving the territory of the previously symptomatic web occurred in 7 (32%; 6
      strokes/1 TIA) patients: 3 <1 week, 2 <first year, and 3 >1 year of follow-up.
      Two recurrences occurred on dual antiplatelet therapy, 3 on antiplatelet
      monotherapy, 1 within 24 hours of thrombolysis, and 1 off antithrombotics. Median
      follow-up was 12.2 (8.0-18.0) months. Sixteen (66%) patients were stented at a
      median 12.2 (7.0-18.7) days after stroke with no periprocedural complications. No
      recurrent strokes/TIAs occurred in stented individuals (median follow-up of 4
      [2.4-12.0] months). CONCLUSIONS: Carotid web is associated with high recurrent
      stroke/TIA risk, despite antithrombotic use, and is amenable to carotid stenting.

PMID- 29018132
TI  - One-Stop Management of Acute Stroke Patients: Minimizing Door-to-Reperfusion
      Times.
AB  - BACKGROUND AND PURPOSE: Intrahospital time delays significantly affect the
      neurological outcome of stroke patients with large-vessel occlusion. This study
      was conducted to determine whether a one-stop management can reduce intrahospital
      times of patients with acute large-vessel occlusion. METHODS: In this
      observational study, we report the first 30 consecutive stroke patients imaged
      and treated in the same room. As part of our protocol, we transported patients
      with a National Institutes of Health Stroke Scale score of >=10 directly to the
      angio suite, bypassing multidetector computed tomography (CT). Preinterventional
      imaging consisted of noncontrast flat detector CT and flat detector CT
      angiography, acquired with an angiography system. Patients with large-vessel
      occlusions remained on the angio table and were treated with mechanical
      thrombectomy; patients with small artery occlusions were treated with intravenous
      thrombolysis, whereas patients with an intracranial hemorrhage and stroke mimics
      were treated as per guidelines. Door-to-groin puncture times were recorded and
      compared with our past results. RESULTS: Thirty patients were transferred
      directly to our angio suite from June to December 2016. The time from symptom
      onset to admission was 105 minutes. Ischemic stroke was diagnosed in 22 of 30
      (73%) patients, 4 of 30 (13.5%) had an intracranial hemorrhage, and 4 of 30
      (13.5) were diagnosed with a Todd's paresis. Time from admission to groin
      puncture was 20.5 minutes. Compared with 44 patients imaged with multidetector CT
      in the first 6 months of 2016, door-to-groin times were significantly reduced
      (54.5 minutes [95% confidence interval, 47-61] versus 20.5 minutes [95%
      confidence interval, 17-26]). CONCLUSIONS: In this small series, a one-stop
      management protocol of selected stroke patients using latest generation flat
      detector CT led to a significant reduction of intrahospital times.

PMID- 29018134
TI  - Neuronal SIRT1 (Silent Information Regulator 2 Homologue 1) Regulates Glycolysis
      and Mediates Resveratrol-Induced Ischemic Tolerance.
AB  - BACKGROUND AND PURPOSE: Resveratrol, at least in part via SIRT1 (silent
      information regulator 2 homologue 1) activation, protects against cerebral
      ischemia when administered 2 days before injury. However, it remains unclear if
      SIRT1 activation must occur, and in which brain cell types, for the induction of
      neuroprotection. We hypothesized that neuronal SIRT1 is essential for resveratrol
      induced ischemic tolerance and sought to characterize the metabolic pathways
      regulated by neuronal Sirt1 at the cellular level in the brain. METHODS: We
      assessed infarct size and functional outcome after transient 60 minute middle
      cerebral artery occlusion in control and inducible, neuronal-specific SIRT1
      knockout mice. Nontargeted primary metabolomics analysis identified putative
      SIRT1-regulated pathways in brain. Glycolytic function was evaluated in acute
      brain slices from adult mice and primary neuronal-enriched cultures under
      ischemic penumbra-like conditions. RESULTS: Resveratrol-induced neuroprotection
      from stroke was lost in neuronal Sirt1 knockout mice. Metabolomics analysis
      revealed alterations in glucose metabolism on deletion of neuronal Sirt1,
      accompanied by transcriptional changes in glucose metabolism machinery.
      Furthermore, glycolytic ATP production was impaired in acute brain slices from
      neuronal Sirt1 knockout mice. Conversely, resveratrol increased glycolytic rate
      in a SIRT1-dependent manner and under ischemic penumbra-like conditions in vitro.
      CONCLUSIONS: Our data demonstrate that resveratrol requires neuronal SIRT1 to
      elicit ischemic tolerance and identify a novel role for SIRT1 in the regulation
      of glycolytic function in brain. Identification of robust neuroprotective
      mechanisms that underlie ischemia tolerance and the metabolic adaptations
      mediated by SIRT1 in brain are crucial for the translation of therapies in
      cerebral ischemia and other neurological disorders.

PMID- 29018135
TI  - Corneal Confocal Microscopy Detects Corneal Nerve Damage in Patients Admitted
      With Acute Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Corneal confocal microscopy can identify corneal nerve
      damage in patients with peripheral and central neurodegeneration. However, the
      use of corneal confocal microscopy in patients presenting with acute ischemic
      stroke is unknown. METHODS: One hundred thirty patients (57 without diabetes
      mellitus [normal glucose tolerance], 32 with impaired glucose tolerance, and 41
      with type 2 diabetes mellitus) admitted with acute ischemic stroke, and 28 age
      matched healthy control participants underwent corneal confocal microscopy to
      quantify corneal nerve fiber density, corneal nerve branch density, and corneal
      nerve fiber length. RESULTS: There was a significant reduction in corneal nerve
      fiber density, corneal nerve branch density, and corneal nerve fiber length in
      stroke patients with normal glucose tolerance (P<0.001, P<0.001, P<0.001),
      impaired glucose tolerance (P=0.004, P<0.001, P=0.002), and type 2 diabetes
      mellitus (P<0.001, P<0.001, P<0.001) compared with controls. HbA1c and
      triglycerides correlated with corneal nerve fiber density (r=-0.187, P=0.03; r=
      0.229 P=0.01), corneal nerve fiber length (r=-0.228, P=0.009; r=-0.285; P=0.001),
      and corneal nerve branch density (r=-0.187, P=0.033; r=-0.229, P=0.01). Multiple
      linear regression showed no independent associations between corneal nerve fiber
      density, corneal nerve branch density, and corneal nerve fiber length and
      relevant risk factors for stroke. CONCLUSIONS: Corneal confocal microscopy is a
      rapid noninvasive ophthalmic imaging technique that identifies corneal nerve
      fiber loss in patients with acute ischemic stroke.

PMID- 29018136
TI  - Dietary Sodium to Potassium Ratio and Risk of Stroke in a Multiethnic Urban
      Population: The Northern Manhattan Study.
AB  - BACKGROUND AND PURPOSE: There is growing evidence that increased dietary sodium
      (Na) intake increases the risk of vascular diseases, including stroke, at least
      in part via an increase in blood pressure. Higher dietary potassium (K), seen
      with increased intake of fruits and vegetables, is associated with lower blood
      pressure. The goal of this study was to determine the association of a dietary
      Na:K with risk of stroke in a multiethnic urban population. METHODS: Stroke-free
      participants from the Northern Manhattan Study, a population-based cohort study
      of stroke incidence, were followed-up for incident stroke. Baseline food
      frequency questionnaires were analyzed for Na and K intake. We estimated the
      hazard ratios and 95% confidence intervals for the association of Na:K with
      incident total stroke using multivariable Cox proportional hazards models.
      RESULTS: Among 2570 participants with dietary data (mean age, 69+/-10 years; 64%
      women; 21% white; 55% Hispanic; 24% black), the mean Na:K ratio was 1.22+/-0.43.
      Over a mean follow-up of 12 years, there were 274 strokes. In adjusted models, a
      higher Na:K ratio was associated with increased risk for stroke (hazard ratio,
      1.6; 95% confidence interval, 1.2-2.1) and specifically ischemic stroke (hazard
      ratio, 1.6; 95% confidence interval, 1.2-2.1). CONCLUSIONS: Na:K intake is an
      independent predictor of stroke risk. Further studies are required to understand
      the joint effect of Na and K intake on risk of cardiovascular disease.

PMID- 29018137
TI  - Incidence and Outcomes of Myocardial Infarction in Patients Admitted With Acute
      Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Data on the incidence and outcomes of acute myocardial
      infarction (AMI) complicating acute ischemic stroke (AIS) are limited. We aim to
      evaluate the incidence, treatment patterns, and outcomes of AMI in patients with
      AIS using a nationwide database. METHODS: The National Inpatient Sample was used
      to identify patient with AIS between 2003 and 2014. Trends of incidence of AMI
      and its associated in-hospital mortality were evaluated. Univariate and
      multivariate logistic regressions were used to evaluate predictors of AMI. The
      impact of AMI on in-hospital outcomes was assessed in a comparative analysis of
      propensity-matched groups of patients with and without AMI. RESULTS: Patients
      with AIS (n=864 043) were identified in the national inpatient sample, of whom 13
      573 patients (1.6%) had an AMI (79.5% non-ST-segment-elevation myocardial
      infarction and 20.5% ST-segment-elevation myocardial infarction). In-hospital
      mortality was 21.4% and 7.1% in propensity-matched cohorts of patients with and
      without AMI, P<0.001. In-hospital length of stay and cost of care were 50% higher
      in the AMI group. In a multivariate logistical regression analysis, the strongest
      predictors of having AMI after AIS were older age, history of coronary artery
      disease, chronic renal insufficiency, undergoing mechanical thrombectomy, and
      rhythm and conduction abnormalities. In the AMI group, undergoing coronary
      angiography and undergoing percutaneous coronary intervention both strongly
      correlated with lower in-hospital mortality (odds ratio, 0.34 [confidence
      interval, 0.23-0.51] and 0.26 [confidence interval, 0.20-0.34], respectively,
      P<0.001). However, these were only performed in 7.5% and 2% of patients,
      respectively. CONCLUSIONS: AMI complicating stroke carries a substantial in
      hospital mortality and cost of care. Patients who underwent coronary angiography
      with or without intervention may have improved survival although it was only
      utilized in a minority of patients. Further studies needed to discern the ideal
      approach in AMI in patients with AIS.

PMID- 29018138
TI  - Endotoxin Preconditioning Reprograms S1 Tubules and Macrophages to Protect the
      Kidney.
AB  - Preconditioning with a low dose of endotoxin confers unparalleled protection
      against otherwise lethal models of sepsis. The mechanisms of preconditioning have
      been investigated extensively in isolated immune cells such as macrophages.
      However, the role of tissue in mediating the protective response generated by
      preconditioning remains unknown. Here, using the kidney as a model organ, we
      investigated cell type-specific responses to preconditioning. Compared with
      preadministration of vehicle, endotoxin preconditioning in the cecal ligation and
      puncture mouse model of sepsis led to significantly enhanced survival and reduced
      bacterial load in several organs. Furthermore, endotoxin preconditioning reduced
      serum levels of proinflammatory cytokines, upregulated molecular pathways
      involved in phagocytosis, and prevented the renal function decline and injury
      induced in mice by a toxic dose of endotoxin. The protective phenotype involved
      the clustering of macrophages around S1 segments of proximal tubules, and full
      renal protection required both macrophages and renal tubular cells. Using
      unbiased S1 transcriptomic and tissue metabolomic approaches, we identified
      multiple protective molecules that were operative in preconditioned animals,
      including molecules involved in antibacterial defense, redox balance, and tissue
      healing. We conclude that preconditioning reprograms macrophages and tubules to
      generate a protective environment, in which tissue health is preserved and
      immunity is controlled yet effective. Endotoxin preconditioning can thus be used
      as a discovery platform, and understanding the role and participation of both
      tissue and macrophages will help refine targeted therapies for sepsis.

PMID- 29018139
TI  - ShcA Adaptor Protein Promotes Nephrin Endocytosis and Is Upregulated in
      Proteinuric Nephropathies.
AB  - Nephrin is a key structural component of the podocyte slit diaphragm, and proper
      expression of nephrin on the cell surface is critical to ensure integrity of the
      blood filtration barrier. Maintenance of nephrin within this unique cell junction
      has been proposed to require dynamic phosphorylation events and endocytic
      recycling, although the molecular mechanisms that control this interplay are
      poorly understood. Here, we investigated the possibility that the phosphotyrosine
      adaptor protein ShcA regulates nephrin turnover. Western blotting and
      immunostaining analysis confirmed that ShcA is expressed in podocytes. In
      immunoprecipitation and pulldown assays, ShcA, via its SH2 domain, was associated
      with several phosphorylated tyrosine residues on nephrin. Overexpression of ShcA
      promoted nephrin tyrosine phosphorylation and reduced nephrin signaling and cell
      surface expression in vitro In a rat model of reversible podocyte injury and
      proteinuria, phosphorylated nephrin temporally colocalized with endocytic
      structures coincident with upregulation of ShcA expression. In vivo biotinylation
      assays confirmed that nephrin expression decreased at the cell surface and
      correspondingly increased in the cytosol during the injury time course. Finally,
      immunostaining in kidney biopsy specimens demonstrated overexpression of ShcA in
      several human proteinuric kidney diseases compared with normal conditions. Our
      results suggest that increases in ShcA perturb nephrin phosphosignaling dynamics,
      leading to aberrant nephrin turnover and slit diaphragm disassembly.

PMID- 29018140
TI  - Incident CKD after Radical or Partial Nephrectomy.
AB  - The comparative effectiveness of partial nephrectomy versus radical nephrectomy
      to preserve kidney function has not been well established. We determined the risk
      of clinically significant (stage 4 and higher) CKD after radical or partial
      nephrectomy among veterans treated for kidney cancer in the Veterans Health
      Administration (2001-2013). Among patients with preoperative eGFR>=30 ml/min per
      1.73 m2, the incidence of CKD stage 4 or higher after radical (n=9759) or partial
      nephrectomy (n=4370) was 7.9% overall. The median time to stage 4 or higher CKD
      after surgery was 5 months, after which few patients progressed. In propensity
      score-matched cohorts, partial nephrectomy associated with a significantly lower
      relative risk of incident CKD stage 4 or higher (hazard ratio, 0.34; 95%
      confidence interval [95% CI], 0.26 to 0.43, versus radical nephrectomy). In a
      parallel analysis of patients with normal or near-normal preoperative kidney
      function (eGFR>=60 ml/min per 1.73 m2), partial nephrectomy was also associated
      with a significantly lower relative risk of incident CKD stage 3b or higher
      (hazard ratio, 0.15; 95% CI, 0.11 to 0.19, versus radical nephrectomy) in
      propensity score-matched cohorts. Competing risk regression models produced
      consistent results. Finally, patients treated with a partial nephrectomy had
      reduced risk of mortality (hazard ratio, 0.55; 95% CI, 0.49 to 0.62). In
      conclusion, compared with radical nephrectomy, partial nephrectomy was associated
      with a marked reduction in the incidence of clinically significant CKD and with
      enhanced survival. Postoperative decline in kidney function occurred mainly in
      the first year after surgery and appeared stable over time.

PMID- 29018141
TI  - Vitamin D regulation of GDNF/Ret signaling in dopaminergic neurons.
AB  - 1,25(OH)2D3 (vitamin D) appears essential for the normal development of
      dopaminergic neurons. Vitamin D affects dopamine synthesis and metabolism as well
      as expression of glial cell line-derived neurotrophic factor (GDNF), which is
      crucial for the survival of dopaminergic neurons. We investigated the role of
      vitamin D on GDNF and its receptors protooncogene tyrosine-protein kinase
      receptor Ret (C-Ret) and GDNF family receptor alpha 1 (GFRalpha1) signaling. To
      this end, we used a developmental vitamin D-deficient rat model and SH-SY5Y cells
      transfected with vitamin D receptor (VDR). The absence of vitamin D ligand in
      gestation reduces C-Ret expression, but not GDNF and GFRalpha1, in embryo
      forebrains. Overexpression of VDR in SH-SY5Y in the absence of ligand (mimicking
      in vivo developmental vitamin D deficiency) also suppressed C-Ret mRNA levels. In
      the presence of vitamin D, C-Ret mRNA and protein expression were increased. The
      chromatin immunoprecipitation results suggested that C-Ret is directly regulated
      by vitamin D via VDR. GDNF was also increased by vitamin D in these cells. Our
      small interfering RNA studies showed that knocking down VDR leads to an increase
      in C-Ret in the absence of ligand. Finally, we confirmed the inverse relationship
      between GFRalpha1 and C-Ret, as knocking down C-Ret led to increases in GFRalpha1
      expression. These data extend our knowledge of the diverse and important roles
      played by vitamin D in dopamine physiology.-Pertile, R. A. N., Cui, X., Hammond,
      L., Eyles, D. W. Vitamin D regulation of GDNF/Ret signaling in dopaminergic
      neurons.

PMID- 29018142
TI  - Adiponectin has a pivotal role in the cardioprotective effect of CP-3(iv), a
      selective CD36 azapeptide ligand, after transient coronary artery occlusion in
      mice.
AB  - CD36 is a multiligand receptor involved in lipid metabolism. We investigated the
      mechanisms underlying the cardioprotective effect of CP-3(iv), an azapeptide
      belonging to a new class of selective CD36 ligands. The role of CP-3(iv) in
      mediating cardioprotection was investigated because CD36 signaling leads to
      activation of peroxisome proliferator-activated receptor-gamma, a transcriptional
      regulator of adiponectin. CP-3(iv) pretreatment reduced infarct size by 54% and
      preserved hemodynamics in C57BL/6 mice subjected to 30 min coronary ligation and
      reperfusion but had no effect in CD36-deficient mice. The effects of CP-3(iv)
      were associated with an increase in circulating adiponectin levels, epididymal
      fat adiponectin gene expression, and adiponectin transcriptional regulators (
      Pparg, Cebpb, Sirt1) after 6 h of reperfusion. Reduced myocardial oxidative
      stress and apoptosis were observed along with an increase in expression of
      myocardial adiponectin target proteins, including cyclooxygenase-2, phospho-AMPK,
      and phospho-Akt. Moreover, CP-3(iv) increased myocardial performance in isolated
      hearts, whereas blockade of adiponectin with an anti-adiponectin antibody
      abrogated it. CP-3(iv) exerts cardioprotection against myocardial ischemia and
      reperfusion (MI/R) injury and dysfunction, at least in part, by increasing
      circulating and myocardial adiponectin levels. Hence, both paracrine and
      endocrine effects of adiponectin may contribute to reduced reactive oxygen
      species generation and apoptosis after MI/R, in a CD36-dependent manner.-Huynh,
      D. N., Bessi, V. L., Menard, L., Piquereau, J., Proulx, C., Febbraio, M., Lubell,
      W. D., Carpentier, A. C., Burelle, Y., Ong, H., Marleau, S. Adiponectin has a
      pivotal role in the cardioprotective effect of CP-3(iv), a selective CD36
      azapeptide ligand, after transient coronary artery occlusion in mice.

PMID- 29018144
TI  - Ogilvie's syndrome treated with an emergency laparotomy, right hemicolectomy and
      end ileostomy.
AB  - Acute colonic pseudo-obstruction (ACPO), or Ogilvie's syndrome, is a rare
      clinical entity in which there is massive non-toxic colonic dilatation in the
      absence of a mechanically obstructing lesion. It is an important yet poorly
      recognised cause of surgical morbidity and mortality occurring typically in
      elderly patients with multiple comorbidities. ACPO can often be reversed
      conservatively with colonoscopic or nasogastric decompression. Surgical
      intervention is seldom necessary. We present a case of Ogilvie's syndrome in
      which a healthy 76-year-old man developed life-threatening pseudo-obstruction
      following rib polytrauma after a mechanical fall. Pneumatosis coli was evident
      radiologically, prompting emergency exploratory laparotomy. Operative findings of
      serosal tearing and ischaemic colitis necessitated treatment with right
      hemicolectomy and ileostomy formation. Microbiological and histopathological
      analyses proved negative for inflammatory, obstructive and infectious colitides.
      The case emphasises the importance of early recognition and timely intervention
      in the management of this rare yet potentially fatal cause of megacolon.

PMID- 29018143
TI  - Knee upside down.
AB  - We present a case of a 19-year-old woman with a forced hyperextension trauma of
      the knee causing a posteromedial fracture, a medial meniscus root tear and
      rupture of the posterior cruciate ligament. The posteromedial fracture of the
      tibial plateau was treated operatively with open reduction and internal fixation.
      Anatomical reconstruction was achieved. Postoperative treatment included
      unlimited flexion and minimal weight bearing. After 3 months, the patient had
      minimal pain after weight bearing and returned to preoperative range of motion.

PMID- 29018145
TI  - Acute pancreatitis with eruptive xanthoma.
AB  - Eruptive xanthomas are benign skin lesions caused by localised deposition of
      lipids in the dermis. Xanthomas can present as early manifestations of systemic
      disorders, which are typically caused by elevated levels of serum triglycerides
      and uncontrolled diabetes. Early recognition and treatment of the underlying
      condition decreases morbidity and mortality. After treatment of the underlying
      metabolic disorders, lesions mostly disappear without leaving scars. We present a
      case with multiple yellowish, erythematous papules on the extremities suggestive
      of eruptive xanthomas admitted to our hospital with acute pancreatitis.

PMID- 29018146
TI  - ANCA and IgA glomerulonephritis all in one: prognosis and complications.
AB  - We present the case of a 75-year-old Hispanic woman with known stage 3 chronic
      kidney disease, long-standing hypertension and type 2 diabetes mellitus who
      presented with right-sided abdominal pain and acute kidney injury, nephrotic
      range proteinuria with positive antimyeloperoxidase antibody. A renal biopsy
      revealed IgA nephropathy with superimposed pauci-immune antineutrophilic
      cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis. The patient
      was treated with pulse intravenous methylprednisolone, cyclophosphamide and
      plasmapheresis. One week after her second dose of cyclophosphamide, she was
      readmitted for infectious complications including influenza A respiratory
      infection, Rothia bacteraemia associated with diarrhoea and herpes zoster of the
      trunk. In this report, we review the prevalence, treatment and prognosis of
      coexistent IgA nephropathy and pauci-immune ANCA-associated crescentic
      glomerulonephritis. We propose that a reduced-dose treatment regimen should be
      considered in elderly patients due to their higher risk of infectious
      complications. Current literature suggests that this treatment approach may
      reduce infectious complications without compromising therapeutic efficacy.

PMID- 29018147
TI  - Acute lymphoblastic leukemia relapse after CD19-targeted chimeric antigen
      receptor T cell therapy.
AB  - CART19 therapy has revolutionized the treatment of CD19+ acute lymphoblastic
      leukemia, demonstrating an unprecedented complete remission rate; however, as
      follow-up prolongs, a high relapse rate after CART19 therapy has emerged as one
      of the major problems. Relapse can be attributed to the loss of leukemic cell
      immunogenicity, diminished function and amount of CART19 cells, and the
      inhibitory bone marrow microenvironment. Although studies to prevent and treat
      relapse have begun, some encouraging results have demonstrated the possibility of
      decreasing the relapse rate. In this review, we focus on the possible mechanisms
      behind relapse. We will summarize and propose strategies to prevent and manage
      relapse on the basis of these potential mechanisms.

PMID- 29018148
TI  - Suppression of CYP1 members of the AHR response by pathogen-associated molecular
      patterns.
AB  - The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor
      that triggers a broad response, which includes the regulation of proinflammatory
      cytokine production by monocytes and macrophages. AHR is negatively regulated by
      a set of genes that it transcriptionally activates, including the AHR repressor
      (Ahrr) and the cytochrome P450 1 (Cyp1) family, which are critical for preventing
      exacerbated AHR activity. An imbalance in these regulatory mechanisms has been
      shown to cause severe defects in lymphoid cells. Therefore, we wanted to assess
      how AHR activation is regulated in monocytes and macrophages in the context of
      innate immune responses induced by pathogen-associated molecular patterns
      (PAMPs). We found that concomitant stimulation of primary human monocytes with
      PAMPs and the AHR agonist 6-formylindolo(3,2-b)carbazole (FICZ) led to a
      selective dose-dependent inhibition of Cyp1 family members induction. Two other
      AHR-dependent genes [Ahrr and NADPH quinone dehydrogenase 1 (Nqo1)] were not
      affected under these conditions, suggesting a split in the AHR regulation by
      PAMPs. This down-regulation of Cyp1 family members did not require de novo
      protein production nor signaling through p38, ERK, or PI3K-Akt-mammalian target
      of rapamycin (mTOR) pathways. Furthermore, such a split regulation of the AHR
      response was more apparent in GM-CSF-derived macrophages, a finding corroborated
      at the functional level by decreased CYP1 activity and decreased proinflammatory
      cytokine production in response to FICZ and LPS. Collectively, our findings
      identify a role for pattern recognition receptor (PRR) signaling in regulating
      the AHR response through selective down-regulation of Cyp1 expression in human
      monocytes and macrophages.

PMID- 29018149
TI  - Hypothesis: stimulation of trained immunity as adjunctive immunotherapy in
      cancer.
AB  - Cancer immunotherapy has steadily progressed during the past decades, with
      checkpoint inhibitor therapy becoming the latest and one of the most promising
      treatments. Despite the progress, most of the patients do not respond or develop
      resistance, and novel additional approaches are needed to improve the clinical
      effectiveness of immunotherapy. Trained immunity (TI) has been described recently
      as a process of epigenetic and metabolic reprogramming that induces a long-term
      enhanced function of innate immune cells. TI is considered to have beneficial
      effects in improving host response to infections and vaccination, and increasing
      evidence suggests that TI-mediated mechanisms also have useful and potent
      antitumor effects. We hypothesized that novel and more effective approaches for
      immunotherapy in cancer may involve induction of TI, alone or in combination with
      current immunotherapies.

PMID- 29018151
TI  - Correction: PRMT5-Selective Inhibitors Suppress Inflammatory T Cell Responses and
      Experimental Autoimmune Encephalomyelitis.

PMID- 29018152
TI  - Correction: Cutting Edge: Helminth Coinfection Blocks Effector Differentiation of
      CD8 T Cells through Alternate Host Th2- and IL-10-Mediated Responses.

PMID- 29018150
TI  - The calcineurin-NFAT axis contributes to host defense during Pseudomonas
      aeruginosa lung infection.
AB  - Infection with the opportunistic pathogen Pseudomonas aeruginosa is effectively
      controlled through tightly coordinated inflammation in healthy individuals.
      Dysregulated inflammation in cystic fibrosis greatly increases susceptibility to
      P. aeruginosa and lung damage. Recently, we identified regulator of calcineurin
      1, a small, conserved protein that suppresses the NFAT pathway by inhibition of
      calcineurin and functions as a central negative regulator of multiple
      inflammatory transcription factors after P. aeruginosa lung infection, implying a
      role for the canonical NFAT pathway in P. aeruginosa infection. Calcineurin is a
      calcium-calmodulin-responsive phosphatase that dephosphorylates NFAT and promotes
      NFAT nuclear translocation and transcriptional activity. The contribution of the
      NFAT pathway to host defense against P. aeruginosa remains poorly characterized.
      In this study, we found that NFAT was rapidly and transiently activated after P.
      aeruginosa infection both in vitro and in vivo. Deficiency of calcineurin Abeta
      caused impaired activation of NFAT and decreased inflammatory cytokine production
      in vivo. Finally, we demonstrated that the cross-talk between the NFAT and NFkB
      pathways coordinately transactivate host response genes during P. aeruginosa
      infection. Together, these results demonstrate for the first time that NFAT is
      activated through calcineurin and interacts with NFkB after P. aeruginosa lung
      infection, and contributes to the host inflammatory response.

PMID- 29018153
TI  - Prednisolone has the same cardiovascular risk profile as hydrocortisone in
      glucocorticoid replacement.
AB  - INTRODUCTION: Patients who need glucocorticoid replacement in both primary and
      secondary adrenal insufficiency (AI) have the choice of either once-daily
      prednisolone or thrice-daily hydrocortisone. A recent European study found no
      difference between prednisolone and hydrocortisone users in several markers
      including glucose, weight, body mass index, systolic and diastolic blood pressure
      and waist circumference, although an increase in cholesterol and low-density
      lipoprotein (LDL) was suggested in a subgroup of these patients. The aim of this
      study was to expand the evidence base for the use of these agents as replacement
      therapy. METHODS: Data from 82 patients on hydrocortisone and 64 patients on
      prednisolone for AI at Imperial College Healthcare NHS Trust were analysed.
      RESULTS: There was no significant difference in total cholesterol, LDL levels or
      any other risk factors between hydrocortisone and prednisolone patients.
      Prednisolone was subjectively significantly more convenient than hydrocortisone
      (P = 0.048). CONCLUSIONS: Prednisolone once daily is more convenient than
      hydrocortisone thrice daily, and there is no difference in the markers of
      cardiovascular risk measured. Because prednisolone mimics the circadian rhythm
      better than other glucocorticoids, it should be considered as an alternative to
      hydrocortisone for AI.

PMID- 29018154
TI  - Usefulness of desmopressin testing to predict relapse during long-term follow-up
      in patients in remission from Cushing's disease.
AB  - Recurrence of Cushing's disease after successful transsphenoidal surgery occurs
      in some 30% of the patients and the response to desmopressin shortly after
      surgery has been proposed as a marker for disease recurrence. The aim of the
      present study was to evaluate the response to desmopressin over time after
      surgery. We tested 56 patients with Cushing's disease in remission after
      transsphenoidal surgery with desmopressin for up to 20 years after surgery. The
      ACTH and cortisol response to desmopressin over time was evaluated in patients on
      long-term remission or undergoing relapse; an increase by at least 27 pg/mL in
      ACTH levels identified responders. The vast majority of patients who underwent
      successful adenomectomy failed to respond to desmopressin after surgery and this
      response pattern was maintained over time in patients on long-term remission.
      Conversely, a response to desmopressin reappeared in patients who subsequently
      developed a recurrence of Cushing's disease, even years prior to frank
      hypercortisolism. It appears therefore that a change in the response pattern to
      desmopressin proves predictive of recurrence of Cushing's disease and may
      indicate which patients require close monitoring.

PMID- 29018155
TI  - Clinical characteristics of 138 Chinese female patients with idiopathic
      hypogonadotropic hypogonadism.
AB  - OBJECTIVE: To evaluate the clinical features of Chinese women with idiopathic
      hypogonadotropic hypogonadism (IHH). METHODS: We retrospectively reviewed the
      clinical characteristics, laboratory and imaging findings, therapeutic management
      and fertility outcomes of 138 women with IHH. All patients had been treated and
      followed up at an academic medical centre during 1990-2016. RESULTS: Among the
      138 patients, 82 patients (59.4%) were diagnosed with normosmic IHH and 56
      patients (40.6%) were diagnosed with Kallmann syndrome (KS). The patients with
      IHH experienced occasional menses (4.3%), spontaneous thelarche (45.7%) or
      spontaneous pubarche (50.7%). Women with thelarche had a higher percentage of
      pubarche (P  < 0.001) and higher gonadotropin concentrations (P  < 0.01).
      Olfactory bulb/sulci abnormalities were found during the magnetic resonance
      imaging (MRI) of all patients with KS. Most patients with IHH had osteopenia and
      low bone age. Among the 16 women who received gonadotropin-releasing hormone
      treatment, ovulation induction or assisted reproductive technology, the clinical
      pregnancy rate was 81.3% and the live birth rate was 68.8%. CONCLUSIONS: The
      present study revealed that the phenotypic spectrum of women with IHH is broader
      than typical primary amenorrhoea with no secondary sexual development, including
      occasional menses, spontaneous thelarche or pubarche. MRI of the olfactory system
      can facilitate the diagnosis of KS. Pregnancy can be achieved after receiving
      appropriate treatment.

PMID- 29018157
TI  - Can liquid-based preparation substitute for conventional smear in thyroid fine
      needle aspiration? A systematic review based on meta-analysis.
AB  - OBJECTIVE: Conventional smear (CS) using fine-needle aspiration cytology (FNAC)
      has been established as the test of choice for diagnosing thyroid lesions,
      despite low sample adequacy and inter-individual variations. Although a liquid
      based preparation (LBP) technique has been recently applied to overcome these
      limitations, its clinical utility and its accuracy over CS are controversial.
      This study aimed to determine the true sensitivity and specificity of LBP in
      thyroid FNAC by meta-analysis. DESIGN: Systematic review with meta-analysis.
      METHODS: We searched major electronic databases (MEDLINE, EMBASE, Cochrane
      library, Google Scholar) with queries of 'thyroid', 'LBP' and 'liquid-based
      cytology'. Original articles including cytohistologic correlation data comparing
      the accuracy of any LBP technique, such as ThinPrep, SurePath and Liqui-Prep,
      with CS were included for qualitative meta-analysis and preparation of
      synthesized reporter-operating curves (sROC). RESULTS: A total of 372 studies
      were screened and 51 original articles were eligible for full-text review;
      finally, 24 studies were chosen for the meta-analysis. Average sample inadequacy
      was significantly lower in two mainstream LBP methods (ThinPrep and SurePath)
      than CS. Specificity and sensitivity by sROC were similar or slightly superior
      for LBP vs CS. Various cytomorphologic changes by each method have been reported.
      CONCLUSIONS: Although a learning curve is essential for adapting to the
      cytomorphologic features of the LBP technique, our results support the use of two
      mainstream LBPs alone in thyroid FNAC that LBP will increase the sample adequacy
      and reduce the workload with similar accuracy. More data and further evaluation
      are needed for the other LBP methods.

PMID- 29018156
TI  - The effect of atorvastatin on pancreatic beta cell requirement in women with
      polycystic ovary syndrome.
AB  - BACKGROUND: There is an increased risk of developing T2DM in women with
      polycystic ovary syndrome (PCOS), and there is evidence that statins improve
      metabolic parameters in these patients. However, there are some data to show that
      statins increase the risk of incipient diabetes. MATERIALS AND METHODS: We have
      previously shown that 12 weeks of atorvastatin improves insulin resistance when
      measured using HOMA-IR. This post hoc analysis was designed to look at the effect
      of atorvastatin on pancreatic beta cell function using HOMA-beta in the same
      study. In this randomised, double-blind placebo controlled study, 40 medication
      naive patients with PCOS were randomised to either atorvastatin 20 mg daily or
      placebo for 3 months. A 3-month extension study for both groups of patients was
      undertaken with metformin 1500 mg daily after completing initial 3 months of
      atorvastatin or placebo. RESULTS: There was a significant reduction in HOMA-beta
      (240 +/- 3.2 vs 177 +/- 2.3; P value <0.01) after 12 weeks of atorvastatin
      treatment, which was maintained by metformin in the subsequent 12 weeks. There
      were no changes in HOMA-beta after the placebo or after subsequent metformin
      treatment.There was no linear correlation between reduction in HOMA-beta with
      improvement of free androgen index (FAI) (r2 = 0.02; P = 0.72), testosterone (r2
      = 0.13; P = 0.49), SHBG (r2 = 0.22; P = 0.48), hsCRP (r2 = 0.19; P = 0.64),
      triglycerides (r2 = 0.09; P = 0.12), total cholesterol (r2 = 0.11; P = 0.32) or
      LDL-C (r2 = 0.19; P = 0.38). CONCLUSION: Treatment with atorvastatin for 12 weeks
      in women with PCOS significantly reduced HOMA-beta. This could be potentially due
      to fall in beta-cell requirement with improvement of insulin resistance rather
      than a reduction of beta-cell function.

PMID- 29018159
TI  - Phenomics of root system architecture: Measuring and analyzing root phenes (By
      Larry York and Guillaume Lobet).
AB  - Summaryplantcell;29/9/tpc.117.tt0917/FIG1F1fig1One of roots' key roles is to
      secure access to water and nutrients for the plant, often in a highly
      heterogeneous and challenging environment. To cope with such function, root
      systems have evolved as highly plastic, responsive and diverse organs. However,
      due to technical constraints, root research has long been stuck in its infancy.
      This teaching tool discusses the relatively young field of root system
      architecture quantification. It introduces the concepts of phenes (like genes,
      but referring to the phenotype), and architectural concepts including morphology,
      geometry, and topology. It concludes by discussing the practical considerations
      linked to the root system architecture quantification (including growth and
      sampling methods), and different data analysis methods. Posted September 20,
      2017.Click HERE to access Teaching Tool Components.

PMID- 29018158
TI  - Suppression and Contrast Normalization in Motion Processing.
AB  - Sensory neurons are activated by a range of stimuli to which they are said to be
      tuned. Usually, they are also suppressed by another set of stimuli that have
      little effect when presented in isolation. The interactions between preferred and
      suppressive stimuli are often quite complex and vary across neurons, even within
      a single area, making it difficult to infer their collective effect on behavioral
      responses mediated by activity across populations of neurons. Here, we
      investigated this issue by measuring, in human subjects (three males), the
      suppressive effect of static masks on the ocular following responses induced by
      moving stimuli. We found a wide range of effects, which depend in a nonlinear and
      nonseparable manner on the spatial frequency, contrast, and spatial location of
      both stimulus and mask. Under some conditions, the presence of the mask can be
      seen as scaling the contrast of the driving stimulus. Under other conditions, the
      effect is more complex, involving also a direct scaling of the behavioral
      response. All of this complexity at the behavioral level can be captured by a
      simple model in which stimulus and mask interact nonlinearly at two stages, one
      monocular and one binocular. The nature of the interactions is compatible with
      those observed at the level of single neurons in primates, usually broadly
      described as divisive normalization, without having to invoke any scaling
      mechanism.SIGNIFICANCE STATEMENT The response of sensory neurons to their
      preferred stimulus is often modulated by stimuli that are not effective when
      presented alone. Individual neurons can exhibit multiple modulatory effects, with
      considerable variability across neurons even in a single area. Such diversity has
      made it difficult to infer the impact of these modulatory mechanisms on
      behavioral responses. Here, we report the effects of a stationary mask on the
      reflexive eye movements induced by a moving stimulus. A model with two stages,
      each incorporating a divisive modulatory mechanism, reproduces our experimental
      results and suggests that qualitative variability of masking effects in cortical
      neurons might arise from differences in the extent to which such effects are
      inherited from earlier stages.

PMID- 29018160
TI  - Dopamine dysregulation syndrome in Parkinson's disease: a systematic review of
      published cases.
AB  - OBJECTIVES: Dopamine dysregulation syndrome (DDS) is an uncommon complication of
      the treatment of Parkinson's disease, characterised by addictive behaviour and
      excessive use of dopaminergic medication. DDS may frequently go unrecognised or
      misdiagnosed. We aimed to clarify current understanding of presentation, risk
      factors, comorbidities and management of DDS. METHODS: Case reports were
      identified through a systematic search of databases (PubMed, Embase) with the
      following terms: dopaminergic dysregulation syndrome, hedonistic homeostatic
      dysregulation, dopamine/levodopa addiction. RESULTS: We reviewed 390 articles,
      identifying 98 cases of DDS. Early-onset Parkinson's disease (67%) and male
      gender (83%) were common. DDS presented with significant physical and social
      impairment, actions to enable or prevent detection of overuse, as well as mood,
      anxiety and motor fluctuations. All DDS cases met DSM-V (Diagnostic and
      Statistical Manual of Mental Disorders, Fifth Edition) substance use disorder
      criteria. Past substance and psychiatric history was present in 15.3% and 10.2%
      of cases. Comorbid impulse control disorders (61%), psychosis (32%) and panic
      attacks (14%) were common. A large variety of management strategies were used;
      only 56% of cases resolving. Sodium valproate was successful in 5/5 cases. The
      response to deep brain stimulation varied. CONCLUSIONS: Given the functional
      impairment, medical and psychiatric consequences and the difficulties of
      treatment, early identification of DDS should be a priority.

PMID- 29018161
TI  - High prevalence of the MYD88 L265P mutation in IgM anti-MAG paraprotein
      associated peripheral neuropathy.

PMID- 29018162
TI  - Clinical utility of amyloid PET imaging with (18)F-florbetapir: a retrospective
      study of 100 patients.
AB  - BACKGROUND AND OBJECTIVE: Amyloid-positron emission tomography (PET) imaging
      (API) detects amyloid-beta pathology early in the course of Alzheimer's disease
      (AD) with high sensitivity and specificity. (18)F-florbetapir (Amyvid) is an
      amyloid-binding PET ligand with a half-life suitable for clinical use outside of
      the research setting. How API affects patient investigation and management in the
      'real-world' arena is unknown. To address this, we retrospectively documented the
      effect of API in patients in the memory clinic. METHODS: We reviewed the
      presenting clinical features, the pre-API and post-API investigations, diagnosis
      and outcomes for the first 100 patients who had API as part of their routine work
      up at the Imperial Memory Centre, a tertiary referral clinic in the UK National
      Health Service. RESULTS: API was primarily used to investigate patients with
      atypical clinical features (56 cases) or those that were young at onset (42
      cases). MRI features of AD did not always predict positive API (67%), and 6 of 23
      patients with MRIs reported as normal were amyloid-PET positive. There were
      significantly more cases categorised as non-AD dementia post-API (from 11 to 23).
      Patients investigated when API was initially available had fewer overall
      investigations and all patients had significantly fewer investigations in total
      post-API. CONCLUSIONS: API has a clear impact on the investigation of young-onset
      or complex dementia while reducing the overall burden of investigations. It was
      most useful in younger patients, atypical presentations or individuals with
      multiple possible causes of cognitive impairment.

PMID- 29018163
TI  - mtDNA copy number associated with age of onset in familial amyloid
      polyneuropathy.
AB  - BACKGROUND: Transthyretin-related familial amyloid polyneuropathy (TTR-FAP
      Val30Met) shows a wide variation in age-at-onset (AO) between generations and
      genders, as in Portuguese families, where women display a later onset and a
      larger anticipation (>10 years). Mitochondrial DNA (mtDNA) copy number was
      assessed to clarify whether it has a modifier effect on AO variability in
      Portuguese patients. METHODS: The mtDNA copy number of 262 samples (175 Val30Met
      TTR carriers and 87 controls (proven Val30Val)) was quantified by quantitative
      real-time PCR. Statistical analysis was performed using IBM SPSS V.23 software.
      RESULTS: This study shows that Val30Met TTR carriers have a significantly higher
      (p<0.001) mean mtDNA copy number than controls. Furthermore, the highest mtDNA
      copy number mean was observed in early-onset patients (AO <40 years).
      Importantly, early-onset offspring showed a significant increase (p=0.002) in the
      mtDNA copy number, when compared with their late AO parents. CONCLUSIONS: The
      present findings suggest, for the first time, that mtDNA copy number may be
      associated with earlier events and may therefore be further explored as a
      potential biomarker for follow-up of TTR-FAP Val30Met carriers.

PMID- 29018166
TI  - Hybrid Atrial Fibrillation Ablation: Current Status and a Look Ahead.

PMID- 29018164
TI  - Termination of Vernakalant-Resistant Atrial Fibrillation by Inhibition of Small
      Conductance Ca2+-Activated K+ Channels in Pigs.
AB  - BACKGROUND: Evidence has emerged that small-conductance Ca2+-activated K+ (SK)
      channels constitute a new target for treatment of atrial fibrillation (AF). SK
      channels are predominantly expressed in the atria as compared with the
      ventricles. Various marketed antiarrhythmic drugs are limited by ventricular
      adverse effects and efficacy loss as AF progresses. METHODS AND RESULTS: A total
      of 43 pigs were used for the studies. AF reversion in conscious long-term
      tachypaced pigs: Pigs were subjected to atrial tachypacing (7 Hz) until they
      developed sustained AF that could not be reverted by vernakalant 4 mg/kg (18.8+/
      3.3 days of atrial tachypacing). When the SK channel inhibitor AP14145 was tested
      in these animals, vernakalant-resistant AF was reverted to sinus rhythm, and
      reinduction of AF by burst pacing (50 Hz) was prevented in 8 of 8 pigs. Effects
      on refractory period and AF duration in open chest pigs: The effects of AP14145
      and vernakalant on the effective refractory periods and acute burst pacing
      induced AF were examined in anaesthetized open chest pigs. Both vernakalant and
      AP14145 significantly prolonged atrial refractoriness and reduced AF duration
      without affecting the ventricular refractoriness or blood pressure in pigs
      subjected to 7 days atrial tachypacing, as well as in sham-operated control pigs.
      CONCLUSIONS: SK currents play a role in porcine atrial repolarization, and
      pharmacological inhibition of these with AP14145 demonstrates antiarrhythmic
      effects in a vernakalant-resistant porcine model of AF. These results suggest SK
      channel blockers as potentially interesting anti-AF drugs.

PMID- 29018167
TI  - Inhibition of Small-Conductance Ca2+-Activated K+ Channels: The Long-Awaited
      Breakthrough for Antiarrhythmic Drug Therapy of Atrial Fibrillation?

PMID- 29018168
TI  - Alternative Approach for Ablation of the Mitral Isthmus.

PMID- 29018165
TI  - Catheter Ablation of the Superolateral Mitral Isthmus Line: A Novel Approach to
      Reduce the Need for Epicardial Ablation.
AB  - BACKGROUND: The mitral isthmus is a critical part of perimitral reentrant
      tachycardia, as well as an important substrate of persistent atrial fibrillation.
      Deployment of an endocardial mitral isthmus line (MIL) with the end point of
      bidirectional block may be challenging and often requires additional epicardial
      ablation within the coronary sinus. METHODS AND RESULTS: The study population
      comprised 114 patients with perimitral flutter who underwent de novo ablation of
      an MIL. The initial 57 patients (group A) underwent catheter ablation using a
      novel superolateral MIL design, connecting the left-sided pulmonary veins with
      the mitral annulus along the posterior base of the left atrial appendage
      visualized by selective angiography. The next 57 patients (group B) served as a
      control group and underwent ablation using a conventional MIL design, connecting
      the left inferior pulmonary vein with the mitral annulus. Bidirectional block was
      achieved in 56 of 57 patients in group A (98.2%) and 50 of 57 patients in group B
      (87.7%; P=0.06). Deployment of a superolateral MIL required significantly less
      ablation from within the coronary sinus (7.0% versus 71.9%; P<0.01). Predictors
      for unsuccessful bidirectional mitral isthmus blockade were the need for
      epicardial ablation from within the coronary sinus (P<0.01) and the total length
      of the MIL (29.3+/-6.35 mm versus 40.8+/-7.29 mm; P=0.005). A higher rate of
      pericardial tamponade was observed in group A (5.2% versus 0%; P=0.24).
      CONCLUSIONS: The superolateral MIL is associated with a high acute success rate
      to achieve bidirectional block using endocardial ablation only with minimal need
      for epicardial ablation from within the coronary sinus.

PMID- 29018169
TI  - Randomized Phase II Trial of Parsatuzumab (Anti-EGFL7) or Placebo in Combination
      with FOLFOX and Bevacizumab for First-Line Metastatic Colorectal Cancer.

PMID- 29018170
TI  - Temperature-activated ion channels in neural crest cells confer maternal fever
      associated birth defects.
AB  - Birth defects of the heart and face are common, and most have no known genetic
      cause, suggesting a role for environmental factors. Maternal fever during the
      first trimester is an environmental risk factor linked to these defects. Neural
      crest cells are precursor populations essential to the development of both at
      risk tissues. We report that two heat-activated transient receptor potential
      (TRP) ion channels, TRPV1 and TRPV4, were present in neural crest cells during
      critical windows of heart and face development. TRPV1 antagonists protected
      against the development of hyperthermia-induced defects in chick embryos.
      Treatment with chemical agonists of TRPV1 or TRPV4 replicated hyperthermia
      induced birth defects in chick and zebrafish embryos. To test whether transient
      TRPV channel permeability in neural crest cells was sufficient to induce these
      defects, we engineered iron-binding modifications to TRPV1 and TRPV4 that enabled
      remote and noninvasive activation of these channels in specific cellular
      locations and at specific developmental times in chick embryos with radio
      frequency electromagnetic fields. Transient stimulation of radio frequency
      controlled TRP channels in neural crest cells replicated fever-associated defects
      in developing chick embryos. Our data provide a previously undescribed mechanism
      for congenital defects, whereby hyperthermia activates ion channels that
      negatively affect fetal development.

PMID- 29018171
TI  - Dual enhancement of T and NK cell function by pulsatile inhibition of SHIP1
      improves antitumor immunity and survival.
AB  - The success of immunotherapy in some cancer patients has revealed the profound
      capacity for cytotoxic lymphocytes to eradicate malignancies. Various
      immunotherapies work by blocking key checkpoint proteins that suppress immune
      cell activity. The phosphatase SHIP1 (SH2-containing inositol polyphosphate 5
      phosphatase) limits signaling from receptors that activate natural killer (NK)
      cells and T cells. However, unexpectedly, genetic ablation studies have shown
      that the effector functions of SHIP1-deficient NK and T cells are compromised in
      vivo. Because chronic activation of immune cells renders them less responsive to
      activating signals (a host mechanism to avoid autoimmunity), we hypothesized that
      the failure of SHIP1 inhibition to induce antitumor immunity in those studies was
      caused by the permanence of genetic ablation. Accordingly, we found that
      reversible and pulsatile inhibition of SHIP1 with 3-alpha-aminocholestane (3AC;
      "SHIPi") increased the antitumor response of NK and CD8+ T cells in vitro and in
      vivo. Transient SHIP1 inhibition in mouse models of lymphoma and colon cancer
      improved the median and long-term tumor-free survival rates. Adoptive transfer
      assays showed evidence of immunological memory to the tumor in hematolymphoid
      cells from SHIPi-treated, long-term surviving mice. The findings suggest that a
      pulsatile regimen of SHIP1 inhibition might be an effective immunotherapy in some
      cancer patients.

PMID- 29018175
TI  - Lessons Learned and to Be Learned About the Use of N-Terminal Pro-B-Type
      Natriuretic Peptide in Heart Failure and Atrial Fibrillation.

PMID- 29018172
TI  - Foxo1 and Foxp1 play opposing roles in regulating the differentiation and
      antitumor activity of TH9 cells programmed by IL-7.
AB  - Tumor-specific CD4+ T helper 9 (TH9) cells, so-called because of their production
      of the cytokine interleukin-9 (IL-9), are a powerful effector T cell subset for
      cancer immunotherapy. We found that pretreatment of naive CD4+ T cells with IL-7
      further enhanced their differentiation into TH9 cells and augmented their
      antitumor activity. IL-7 markedly increased the abundance of the histone
      acetyltransferase p300 by activating the STAT5 and PI3K-AKT-mTOR signaling
      pathways and promoting the acetylation of histones at the Il9 promoter. As a
      result, the transcriptional regulator Foxo1 was dephosphorylated and translocated
      to the nucleus, bound to the Il9 promoter, and induced the production of IL-9
      protein. In contrast, Foxp1, which bound to the Il9 promoter in naive CD4+ T
      cells and inhibited Il9 expression, was outcompeted for binding to the Il9
      promoter by Foxo1 and translocated to the cytoplasm. Furthermore, forced
      expression of Foxo1 or a deficiency in Foxp1 in CD4+ T cells markedly increased
      the production of IL-9, whereas a deficiency in Foxo1 inhibited the ability of IL
      7 to enhance the differentiation and antitumor activity of TH9 cells. Thus, we
      identified the roles of Foxo1 as a positive regulator and Foxp1 as a negative
      regulator of TH9 cell differentiation and antitumor activity, which may provide
      potential targets for cancer immunotherapy.

PMID- 29018173
TI  - A pilot study of surgical telementoring for leg fasciotomy.
AB  - INTRODUCTION: Acute extremity compartment syndrome requires rapid decompression.
      In remote locations, distance, weather and logistics may delay the evacuation of
      patients with extremity trauma beyond the desired timeline for compartment
      release. The aim of this study was to establish the feasibility of performing
      telementored surgery for leg compartment release and to identify methodological
      issues relevant for future research. METHODS: Three anaethetists and one critical
      care physician were recruited as operators. They were directed to perform a two
      incision leg fasciotomy on a Thiel-embalmed cadaver under the guidance of a
      remotely located orthopaedic surgeon. The operating physician and the surgeon
      (mentor) were connected through software that allows for real-time supervision
      and the use of a virtual pointer overlaid onto the surgical field. Two
      experienced orthopaedic traumatologists independently assessed the adequacy of
      compartment decompression and the presence of iatrogenic complications. RESULTS:
      14 of 16 compartments (in four leg specimens) were felt to have been completely
      released. The first evaluator considered that the deep posterior compartment was
      incompletely released in two specimens. The second evaluator considered that the
      superficial posterior compartment was incompletely released in two specimens. The
      only complication was a large laceration of the soleus muscle that occurred
      during a period of blurred video signal attributed to a drop in bandwidth.
      CONCLUSIONS: This study suggests that surgical telementoring may enable
      physicians to safely perform two-incision leg fasciotomy in remote environments.
      This could improve the chances of limb salvage when compartment syndrome occurs
      far from surgical care. We found interobserver variation in the assessment of
      compartment release, which should be considered in the design of future research
      protocols.

PMID- 29018177
TI  - A challenge to unqualified medical confidentiality.
AB  - Medical personnel sometimes face a seeming conflict between a duty to respect
      patient confidentiality and a duty to warn or protect endangered third parties.
      The conventional answer to dilemmas of this sort is that, in certain
      circumstances, medical professionals have an obligation to breach
      confidentiality. Kenneth Kipnis has argued, however, that the conventional wisdom
      on the nature of medical confidentiality is mistaken. Kipnis argues that the
      obligation to respect patient confidentiality is unqualified or absolute, since
      unqualified policies can save more lives in the long run. In this paper, I
      identify the form of Kipnis's argument and present a challenge to it. I conclude
      that, as matters stand now, a qualified confidentiality policy is the more
      rational choice.

PMID- 29018174
TI  - Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide Levels in Heart
      Failure Patients With and Without Atrial Fibrillation.
AB  - BACKGROUND: Patients with heart failure (HF) and atrial fibrillation (AF) have
      higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic
      peptide) than HF patients without AF. There is uncertainty about the prognostic
      importance of a given concentration of NT-proBNP in HF patients with and without
      AF. We investigated this question in a large cohort of patients with HF and
      reduced ejection fraction. METHODS AND RESULTS: We studied 14 737 patients with
      HF and reduced ejection fraction and a measurement of NT-proBNP at time of
      screening, enrolled in either the PARADIGM-HF trial (Prospective Comparison of
      ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart
      Failure) or the ATMOSPHERE trial (Aliskiren Trial to Minimize Outcomes in
      Patients With Heart Failure), of whom 3575 (24%) had AF on their baseline ECG.
      Median (Q1, Q3) levels of NT-proBNP were 1817 pg/mL (1095-3266 pg/mL) in those
      with AF and 1271 pg/mL (703-2569 pg/mL) in those without (P<0.0001). Patients
      with AF were older (67 versus 62 years), had worse New York Heart Association
      class (III/IV; 36% versus 24%), and experienced fewer previous HF
      hospitalizations (52% versus 61%) or myocardial infarction (30% versus 46%); all
      P<0.001. We categorized patients with and without AF into 5 NT-proBNP bands:
      <400, 400 to 999 (reference), 1000 to 1999, 2000 to 2999, and >=3000 pg/mL. For
      the primary composite outcome of cardiovascular death or HF hospitalization,
      event rates differed for patients with and without AF in the lowest band (<400
      pg/mL; 8.2 versus 5.0 per 100 patient-years), but not for the higher bands (400
      999 pg/mL, 7.4 versus 7.7 per 100 patient-years; 1000-1999 pg/mL, 9.8 versus 11.4
      per 100 patient-year; 2000-2999 pg/mL, 13.5 versus 13.4 per 100 patient-years;
      >=3000 pg/mL, 22.7 versus 23.0 per 100 patient-years). These findings were
      consistent whether NT-proBNP was examined as a categorical or continuous variable
      and before and after adjustment for other prognostic variables. We found similar
      results for the components of the composite outcome and all-cause mortality.
      CONCLUSIONS: HF and reduced ejection fraction patients with AF had higher NT
      proBNP than those without AF. However, above a concentration of 400 pg/mL
      (representing most patients in each group), NT-proBNP had similar predictive
      value for adverse cardiovascular outcomes, irrespective of AF status. CLINICAL
      TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier
      NCT00853658 (ATMOSPHERE) and NCT01035255 (PARADIGM-HF).

PMID- 29018176
TI  - In defence of governance: ethics review and social research.
AB  - There is a growing body of literature that has sought to undermine systems of
      ethical regulation, and governance more generally, within the social sciences. In
      this paper, we argue that any general claim for a system of research ethics
      governance in social research depends on clarifying the nature of the stake that
      society has in research. We show that certain accounts of this stake-protecting
      researchers' freedoms; ensuring accountability for resources; safeguarding
      welfare; and supporting democracy-raise relevant ethical considerations that are
      reasonably contested. However, these accounts cannot underpin a general claim in
      favour of, or against, a system of research ethics governance. Instead, we defend
      governance in social research on the grounds that research, as an
      institutionalised form of enquiry, is a constitutive element of human
      flourishing, and that society ought to be concerned with the flourishing of its
      members. We conclude by considering the governance arrangements that follow from,
      and are justified by, our arguments.

PMID- 29018178
TI  - Attitudes of paediatric and obstetric specialists towards prenatal surgery for
      lethal and non-lethal conditions.
AB  - BACKGROUND: While prenatal surgery historically was performed exclusively for
      lethal conditions, today intrauterine surgery is also performed to decrease
      postnatal disabilities for non-lethal conditions. We sought to describe
      physicians' attitudes about prenatal surgery for lethal and non-lethal conditions
      and to elucidate characteristics associated with these attitudes. METHODS: Survey
      of 1200 paediatric surgeons, neonatologists and maternal-fetal medicine
      specialists (MFMs). RESULTS: Of 1176 eligible physicians, 670 (57%) responded
      (range by specialty, 54%-60%). In the setting of a lethal condition for which
      prenatal surgery would likely result in the child surviving with a severe
      disability, most respondents either disagreed (59%) or strongly disagreed (19%)
      that they would recommend the surgery. Male physicians were twice as likely to
      recommend surgery for the lethal condition, as were physicians who believe that
      abortion is morally wrong (OR 1.75; 95%CI 1.0 to 3.05). Older physicians were
      less likely to recommend surgery (OR 0.57; 95%CI 0.36 to 0.88). For non-lethal
      conditions, most respondents agreed (66% somewhat, 4% strongly) that they would
      recommend prenatal surgery, even if the surgery increases the risk of prematurity
      or fetal death. Compared with MFMs, surgeons were less likely to recommend such
      surgery, as were physicians not affiliated with a fetal centre, and physicians
      who were religious (ORs range from 0.45 to 0.64). CONCLUSION: Physician's
      attitudes about prenatal surgery relate to physicians' beliefs about disability
      as well as demographic, cultural and religious characteristics. Given the variety
      of views, parents are likely to receive different recommendations from their
      doctors about the preferable treatment choice.

PMID- 29018179
TI  - Exhaled isoprene for monitoring recovery from acute hypoxic stress.
AB  - Hypoxia-like incidents in-flight have increased over the past decade causing
      severe safety concerns across the aviation community. As a result, the need to
      monitor flight crews in real-time for the onset of hypoxic conditions is
      paramount for continued aeronautical safety. Here, hypoxic events were simulated
      in the laboratory via a reduced oxygen-breathing device to determine the effect
      of recovery gas oxygen concentration (21% and 100%) on exhaled breath volatile
      organic compound composition. Data from samples collected both serially
      (throughout the exposure), prior to, and following exposures yielded 326
      statistically significant features, 203 of which were unique. Of those, 72
      features were tentatively identified while 51 were verified with authentic
      standards. A comparison of samples collected serially between recovery and
      hypoxia time points shows a statistically significant reduction in exhaled breath
      isoprene (2-methyl-1,3-butadiene, log2 FC -0.399, p = 0.005, FDR = 0.034, q =
      0.033), however no significant difference in isoprene abundance was observed when
      comparing recovery gases (21% or 100% O2, p = 0.152). Furthermore, examination of
      pre-/post-exposure 1 l bag breath samples illustrate an overall increase in
      exhaled isoprene abundance post-exposure (log2 FC 0.393, p = 0.005, FDR = 0.094,
      q = 0.033) but again no significant difference between recovery gas (21% and
      100%, p = 0.798) was observed. A statistically significant difference in trend
      was observed between isoprene abundance and recovery gases O2 concentration when
      plotted against minimum oxygen saturation (p = 0.0419 100% O2, p = 0.7034 21%
      O2). Collectively, these results suggest exhaled isoprene is dynamic in the
      laboratory ROBD setup and additional experimentation will be required to fully
      understand the dynamics of isoprene in response to acute hypoxic stress.

PMID- 29018180
TI  - Association between neuroendocrine tumor of the ileum and two colonic primary
      malignancies. A case report and review of literature.
AB  - BACKGROUND: A high rate of association between neuroendocrine tumors (NETs) and
      secondary primary malignancy (SPM) has been described in literature and this
      association can occur either in a synchronous or a metachronous presentation. A
      wide range of hypothesis has been postulated to explain the high rate of
      association between NETs and SPM, without definitive conclusions. CASE
      PRESENTATION: We report a case of an ileal neuroendocrine tumor found
      incidentally at the histologic examination of the surgical specimen in a 72 years
      old male underwent to right hemi colectomy for two colic adenomatous polips with
      high grade dysplasia. CONCLUSION: Large multicentric epidemiological studies
      should be considered to assess the association between NETs and SPM. KEY WORDS:
      Neuroendocrine tumors (NETs), Progression-Free Survival (PFS), Secondary primary
      malignancy (SPM).

PMID- 29018184
TI  - Correspondence: Numerical modelling of the PERM anomaly and the Emeishan large
      igneous province.

PMID- 29018183
TI  - A Case of Left Renal Vein Ligation in a Patient with Solitary Left Kidney
      Undergoing Liver Transplantation to Control Splenorenal Shunt and Improve Portal
      Venous Flow.
AB  - BACKGROUND Adequate portal venous flow is required for successful liver
      transplantation. Reduced venous flow and blood flow 'steal' by collateral vessels
      are a concern, and when there is a prominent splenorenal shunt present, ligation
      of the left renal vein has been recommended to improve portal venous blood flow.
      CASE REPORT A 51-year-old man who had undergone right nephrectomy in childhood
      required liver transplantation for liver cirrhosis and hepatocellular carcinoma
      due to hepatitis C virus (HCV) infection. The patient had no other comorbidity
      and no history of hepatorenal syndrome. At transplantation surgery, portal venous
      flow was poor and did not improve with ligation of shunt veins, but ligation of
      the left renal vein improved portal venous flow. On the first and fifth
      postoperative days, the patient was treated with basiliximab, a chimeric
      monoclonal antibody to the IL-2 receptor, and methylprednisolone. The calcineurin
      inhibitor, tacrolimus, was introduced on the fifth postoperative day. On the
      sixteenth postoperative day, renal color Doppler ultrasound showed normal left
      renal parenchyma; hepatic Doppler ultrasound showed good portal vein flow and
      preserved hepatic parenchyma in the liver transplant. CONCLUSIONS This case
      report has shown that in a patient with a single left kidney, left renal vein
      ligation is feasible and safe in a patient with no other risk factors for renal
      impairment following liver transplantation. Modification of postoperative
      immunosuppression to avoid calcineurin inhibitors in the very early postoperative
      phase may be important in promoting good recovery of renal function and to avoid
      the need for postoperative renal dialysis.

PMID- 29018182
TI  - Role of Nitric Oxide Pathway in Development and Progression of Chronic Kidney
      Disease in Rats Sensitive and Resistant to its Occurrence in an Experimental
      Model of 5/6 Nephrectomy.
AB  - BACKGROUND Understanding the mechanisms conditioning development of chronic
      kidney disease (CKD) is still a challenge. The aim of this study was to evaluate
      the activity of the intrarenal nitric oxide (NO) pathway in the context of
      sensitivity or resistance of different animal strains to the development and
      degree of renal failure. MATERIAL AND METHODS Two rat strains were used: Wistar
      (WR) and Sprague-Dawley rats (SDR) in a model of CKD - 5/6 nephrectomy. We
      assessed parameters of renal failure and expression of nitric oxide synthase
      (NOS) isoforms in renal cortex and medulla. RESULTS We did not observe renal
      failure in WR, and CKD developed in SDR with increase of creatinine and urea
      concentration as well as decrease of diuresis and glomerular filtration. In the
      renal cortex, baseline expression of NOS2 was higher in WR than in SDR. 5/6
      nephrectomy resulted in reduction of NOS2 in both strains and NOS3 in WR. In the
      renal medulla, baseline NOS2 expression was higher in SDR, and nephrectomy
      resulted in its decrease only in SDR. Although baseline NOS3 expression was
      higher in SDR, the NOS3 expression after nephrectomy was higher in WR rats.
      CONCLUSIONS In model of CKD - 5/6 nephrectomy, SDR proved to be sensitive and WR
      resistant to development of CKD. The intrarenal activity of the nitric oxide
      pathway was the factor that differentiated both strains. This mechanism may be
      responsible for insensitivity of WR to development of renal failure in this model
      of CKD.

PMID- 29018185
TI  - Laterally extended atomically precise graphene nanoribbons with improved
      electrical conductivity for efficient gas sensing.
AB  - Narrow atomically precise graphene nanoribbons hold great promise for electronic
      and optoelectronic applications, but the previously demonstrated nanoribbon-based
      devices typically suffer from low currents and mobilities. In this study, we
      explored the idea of lateral extension of graphene nanoribbons for improving
      their electrical conductivity. We started with a conventional chevron graphene
      nanoribbon, and designed its laterally extended variant. We synthesized these new
      graphene nanoribbons in solution and found that the lateral extension results in
      decrease of their electronic bandgap and improvement in the electrical
      conductivity of nanoribbon-based thin films. These films were employed in gas
      sensors and an electronic nose system, which showed improved responsivities to
      low molecular weight alcohols compared to similar sensors based on benchmark
      graphitic materials, such as graphene and reduced graphene oxide, and a reliable
      analyte recognition. This study shows the methodology for designing new
      atomically precise graphene nanoribbons with improved properties, their bottom-up
      synthesis, characterization, processing and implementation in electronic
      devices.Atomically precise graphene nanoribbons are a promising platform for
      tailored electron transport, yet they suffer from low conductivity. Here, the
      authors devise a strategy to laterally extend conventional chevron nanoribbons,
      thus achieving increased electrical conductivity and improved chemical sensing
      capabilities.

PMID- 29018186
TI  - Microfluidics with fluid walls.
AB  - Microfluidics has great potential, but the complexity of fabricating and
      operating devices has limited its use. Here we describe a method - Freestyle
      Fluidics - that overcomes many key limitations. In this method, liquids are
      confined by fluid (not solid) walls. Aqueous circuits with any 2D shape are
      printed in seconds on plastic or glass Petri dishes; then, interfacial forces pin
      liquids to substrates, and overlaying an immiscible liquid prevents evaporation.
      Confining fluid walls are pliant and resilient; they self-heal when liquids are
      pipetted through them. We drive flow through a wide range of circuits passively
      by manipulating surface tension and hydrostatic pressure, and actively using
      external pumps. Finally, we validate the technology with two challenging
      applications - triggering an inflammatory response in human cells and chemotaxis
      in bacterial biofilms. This approach provides a powerful and versatile
      alternative to traditional microfluidics.The complexity of fabricating and
      operating microfluidic devices limits their use. Walsh et al. describe a method
      in which circuits are printed as quickly and simply as writing with a pen, and
      liquids in them are confined by fluid instead of solid walls.

PMID- 29018187
TI  - Interconnected subsets of memory follicular helper T cells have different
      effector functions.
AB  - Follicular helper T cells regulate high-affinity antibody production. Memory
      follicular helper T cells can be local in draining lymphoid organs and circulate
      in the blood, but the underlying mechanisms of this subdivision are unresolved.
      Here we show that both memory follicular helper T subsets sustain B-cell
      responses after reactivation. Local cells promote more plasma cell
      differentiation, whereas circulating cells promote more secondary germinal
      centers. In parallel, local memory B cells are homogeneous and programmed to
      become plasma cells, whereas circulating memory B cells are able to rediversify.
      Local memory follicular helper T cells have higher affinity T-cell receptors,
      which correlates with expression of peptide MHC-II at the surface of local memory
      B cells only. Blocking T-cell receptor-peptide MHC-II interactions induces the
      release of local memory follicular helper T cells in the circulating compartment.
      Our studies show that memory follicular helper T localization is highly
      intertwined with memory B cells, a finding that has important implications for
      vaccine design.Tfh cells can differentiate into memory cells. Here the authors
      describe distinct functional and phenotypic profiles of these memory Tfh cells
      dependent on their anatomical localization to the lymphoid organs or to the
      circulation.

PMID- 29018188
TI  - Cardioprotection induced in a mouse model of neuropathic pain via anterior
      nucleus of paraventricular thalamus.
AB  - Myocardial infarction is the leading cause of death worldwide. Restoration of
      blood flow rescues myocardium but also causes ischemia-reperfusion injury. Here,
      we show that in a mouse model of chronic neuropathic pain, ischemia-reperfusion
      injury following myocardial infarction is reduced, and this cardioprotection is
      induced via an anterior nucleus of paraventricular thalamus (PVA)-dependent
      parasympathetic pathway. Pharmacological inhibition of extracellular signal
      regulated kinase activation in the PVA abolishes neuropathic pain-induced
      cardioprotection, whereas activation of PVA neurons pharmacologically, or
      optogenetic stimulation, is sufficient to induce cardioprotection. Furthermore,
      neuropathic injury and optogenetic stimulation of PVA neurons reduce the heart
      rate. These results suggest that the parasympathetic nerve is responsible for
      this unexpected cardioprotective effect of chronic neuropathic pain in
      mice.Various forms of preconditioning can prevent ischemic-reperfusion injury
      after myocardial infarction. Here, the authors show that in mice, the presence of
      chronic neuropathic pain can have a cardioprotective effect, and that this is
      dependent on neural activation in the paraventricular thalamus.

PMID- 29018190
TI  - Color-selective photodetection from intermediate colloidal quantum dots buried in
      amorphous-oxide semiconductors.
AB  - We report color-selective photodetection from intermediate, monolayered, quantum
      dots buried in between amorphous-oxide semiconductors. The proposed active
      channel in phototransistors is a hybrid configuration of oxide-quantum dot-oxide
      layers, where the gate-tunable electrical property of silicon-doped, indium-zinc
      oxide layers is incorporated with the color-selective properties of quantum dots.
      A remarkably high detectivity (8.1 * 1013 Jones) is obtained, along with three
      major findings: fast charge separation in monolayered quantum dots; efficient
      charge transport through high-mobility oxide layers (20 cm2 V-1 s-1); and gate
      tunable drain-current modulation. Particularly, the fast charge separation rate
      of 3.3 ns-1 measured with time-resolved photoluminescence is attributed to the
      intermediate quantum dots buried in oxide layers. These results facilitate the
      realization of efficient color-selective detection exhibiting a photoconductive
      gain of 107, obtained using a room-temperature deposition of oxide layers and a
      solution process of quantum dots. This work offers promising opportunities in
      emerging applications for color detection with sensitivity, transparency, and
      flexibility.The development of highly sensitive photodetectors is important for
      image sensing and optical communication applications. Cho et al., report ultra
      sensitive photodetectors based on monolayered quantum dots buried in between
      amorphous-oxide semiconductors and demonstrate color-detecting logic gates.

PMID- 29018189
TI  - The gut microbiome in atherosclerotic cardiovascular disease.
AB  - The gut microbiota has been linked to cardiovascular diseases. However, the
      composition and functional capacity of the gut microbiome in relation to
      cardiovascular diseases have not been systematically examined. Here, we perform a
      metagenome-wide association study on stools from 218 individuals with
      atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD
      gut microbiome deviates from the healthy status by increased abundance of
      Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for
      metabolism or transport of several molecules important for cardiovascular health.
      Although drug treatment represents a confounding factor, ACVD status, and not
      current drug use, is the major distinguishing feature in this cohort. We identify
      common themes by comparison with gut microbiome data associated with other
      cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and
      rheumatoid arthritis. Our data represent a comprehensive resource for further
      investigations on the role of the gut microbiome in promoting or preventing ACVD
      as well as other related diseases.The gut microbiota may play a role in
      cardiovascular diseases. Here, the authors perform a metagenome-wide association
      study on stools from individuals with atherosclerotic cardiovascular disease and
      healthy controls, identifying microbial strains and functions associated with the
      disease.

PMID- 29018191
TI  - D-serine released by astrocytes in brainstem regulates breathing response to CO2
      levels.
AB  - Central chemoreception is essential for adjusting breathing to physiological
      demands, and for maintaining CO2 and pH homeostasis in the brain. CO2-induced ATP
      release from brainstem astrocytes stimulates breathing. NMDA receptor (NMDAR)
      antagonism reduces the CO2-induced hyperventilation by unknown mechanisms. Here
      we show that astrocytes in the mouse caudal medullary brainstem can synthesize,
      store, and release D-serine, an agonist for the glycine-binding site of the
      NMDAR, in response to elevated CO2 levels. We show that systemic and raphe
      nucleus D-serine administration to awake, unrestrained mice increases the
      respiratory frequency. Application of D-serine to brainstem slices also increases
      respiratory frequency, which was prevented by NMDAR blockade. Inhibition of D
      serine synthesis, enzymatic degradation of D-serine, or the sodium fluoroacetate
      induced impairment of astrocyte functions decrease the basal respiratory
      frequency and the CO2-induced respiratory response in vivo and in vitro. Our
      findings suggest that astrocytic release of D-serine may account for the
      glutamatergic contribution to central chemoreception.Astrocytes are involved in
      chemoreception in brainstem areas that regulate breathing rhythm, and astrocytes
      are known to release D-serine. Here the authors show that astrocyte release of D
      serine contributes to CO2 sensing and breathing in brainstem slices, and in vivo
      in awake unrestrained mice.

PMID- 29018193
TI  - Coherent optomechanical state transfer between disparate mechanical resonators.
AB  - Systems of coupled mechanical resonators are useful for quantum information
      processing and fundamental tests of physics. Direct coupling is only possible
      with resonators of very similar frequency, but by using an intermediary optical
      mode, non-degenerate modes can interact and be independently controlled in a
      single optical cavity. Here we demonstrate coherent optomechanical state swapping
      between two spatially and frequency separated resonators with a mass ratio of 4.
      We find that, by using two laser beams far detuned from an optical cavity
      resonance, efficient state transfer is possible. Although the demonstration is
      classical, the same technique can be used to generate entanglement between
      oscillators in the quantum regime.Coupled mechanical resonators where each mode
      can be separately controlled are a promising system for quantum information
      processing. Here, Weaver et al. demonstrate coherent swapping of optomechanical
      states between two separate resonators.

PMID- 29018192
TI  - Simultaneous evolutionary expansion and constraint of genomic heterogeneity in
      multifocal lung cancer.
AB  - Recent genomic analyses have revealed substantial tumor heterogeneity across
      various cancers. However, it remains unclear whether and how genomic
      heterogeneity is constrained during tumor evolution. Here, we sequence a unique
      cohort of multiple synchronous lung cancers (MSLCs) to determine the relative
      diversity and uniformity of genetic drivers upon identical germline and
      environmental background. We find that each multicentric primary tumor harbors
      distinct oncogenic alterations, including novel mutations that are experimentally
      demonstrated to be functional and therapeutically targetable. However, functional
      studies show a strikingly constrained tumorigenic pathway underlying
      heterogeneous genetic variants. These results suggest that although the mutation
      specific routes that cells take during oncogenesis are stochastic, genetic
      trajectories may be constrained by selection for functional convergence on key
      signaling pathways. Our findings highlight the robust evolutionary pressures that
      simultaneously shape the expansion and constraint of genomic diversity, a
      principle that holds important implications for understanding tumor evolution and
      optimizing therapeutic strategies.Across cancer types tumor heterogeneity has
      been observed, but how this relates to tumor evolution is unclear. Here, the
      authors sequence multiple synchronous lung cancers, highlighting the evolutionary
      pressures that simultaneously shape the expansion and constraint of genomic
      heterogeneity.

PMID- 29018195
TI  - Prior preferences beneficially influence social and non-social learning.
AB  - Our personal preferences affect a broad array of social behaviors. This includes
      the way we learn the preferences of others, an ability that often relies on
      limited or ambiguous information. Here we report an egocentric influence on this
      type of social learning that is reflected in both performance and response times.
      Using computational models that combine inter-trial learning and intra-trial
      choice, we find transient effects of participants' preferences on the learning
      process, through the influence of priors, and persistent effects on the choice
      process. A second experiment shows that these effects generalize to non-social
      learning, though participants in the social learning experiment appeared to
      additionally benefit by using their knowledge about the popularity of certain
      preferences. We further find that the domain-general egocentric influences we
      identify can yield performance advantages in uncertain environments.People often
      assume that other people share their preferences, but how exactly this bias
      manifests itself in learning and decision-making is unclear. Here, authors show
      that a person's own preferences influence learning in both social and non-social
      situations, and that this bias improves performance.

PMID- 29018196
TI  - Cenozoic global cooling and increased seawater Mg/Ca via reduced reverse
      weathering.
AB  - Authigenic clay minerals formed on or in the seafloor occur in every type of
      marine sediment. They are recognized to be a major sink of many elements in the
      ocean but are difficult to study directly due to dilution by detrital clay
      minerals. The extremely low dust fluxes and marine sedimentation rates in the
      South Pacific Gyre (SPG) provide a unique opportunity to examine relatively
      undiluted authigenic clay. Here, using Mg isotopes and element concentrations
      combined with multivariate statistical modeling, we fingerprint and quantify the
      abundance of authigenic clay within SPG sediment. Key reactants include volcanic
      ash (source of reactive aluminium) and reactive biogenic silica on or shallowly
      buried within the seafloor. Our results, together with previous studies, suggest
      that global reorganizations of biogenic silica burial over the Cenozoic reduced
      marine authigenic clay formation, contributing to the rise in seawater Mg/Ca and
      decline in atmospheric CO2 over the past 50 million years.Reverse weathering
      reactions on or in the seafloor are a major sink of many elements and alkalinity
      in seawater. Here, the authors show how reduced rates of reverse weathering may
      be responsible for global cooling and increased seawater Mg/Ca over the past 50
      million years.

PMID- 29018194
TI  - PNLDC1 is essential for piRNA 3' end trimming and transposon silencing during
      spermatogenesis in mice.
AB  - Piwi-interacting RNAs are small regulatory RNAs with key roles in transposon
      silencing and regulation of gametogenesis. The production of mature piwi
      interacting RNAs requires a critical step of trimming piwi-interacting RNA
      intermediates to achieve optimally sized piwi-interacting RNAs. The poly(A)
      specific ribonuclease family deadenylase PNLDC1 is implicated in piwi-interacting
      RNA trimming in silkworms. The physiological function of PNLDC1 in mammals
      remains unknown. Using Pnldc1-deficient mice, here we show that PNLDC1 is
      required for piwi-interacting RNA biogenesis, transposon silencing, and
      spermatogenesis. Pnldc1 mutation in mice inhibits piwi-interacting RNA trimming
      and causes accumulation of untrimmed piwi-interacting RNA intermediates with 3'
      end extension, leading to severe reduction of mature piwi-interacting RNAs in the
      testis. Pnldc1 mutant mice exhibit disrupted LINE1 retrotransposon silencing and
      defect in spermiogenesis. Together, these results define PNLDC1 as a mammalian
      piwi-interacting RNA biogenesis factor that protects the germline genome and
      ensures normal sperm production in mice.piRNAs are regulatory RNAs that play a
      critical role in transposon silencing and gametogenesis. Here, the authors
      provide evidence that mammalian PNLDC1 is a regulator of piRNA biogenesis,
      transposon silencing and spermatogenesis, protecting the germline genome in mice.

PMID- 29018198
TI  - Plume-subduction interaction forms large auriferous provinces.
AB  - Gold enrichment at the crustal or mantle source has been proposed as a key
      ingredient in the production of giant gold deposits and districts. However, the
      lithospheric-scale processes controlling gold endowment in a given metallogenic
      province remain unclear. Here we provide the first direct evidence of native gold
      in the mantle beneath the Deseado Massif in Patagonia that links an enriched
      mantle source to the occurrence of a large auriferous province in the overlying
      crust. A precursor stage of mantle refertilisation by plume-derived melts
      generated a gold-rich mantle source during the Early Jurassic. The interplay of
      this enriched mantle domain and subduction-related fluids released during the
      Middle-Late Jurassic resulted in optimal conditions to produce the ore-forming
      magmas that generated the gold deposits. Our study highlights that
      refertilisation of the subcontinental lithospheric mantle is a key factor in
      forming large metallogenic provinces in the Earth's crust, thus providing an
      alternative view to current crust-related enrichment models.The lithospheric
      controls on giant gold deposits remain unclear. Here, the authors show evidence
      for native gold in the mantle from the Deseado Massif in Patagonia demonstrating
      that refertilisation of the lithospheric mantle is key in forming metallogenic
      provinces.

PMID- 29018197
TI  - The chromosomal organization of horizontal gene transfer in bacteria.
AB  - Bacterial adaptation is accelerated by the acquisition of novel traits through
      horizontal gene transfer, but the integration of these genes affects genome
      organization. We found that transferred genes are concentrated in only ~1% of the
      chromosomal regions (hotspots) in 80 bacterial species. This concentration
      increases with genome size and with the rate of transfer. Hotspots diversify by
      rapid gene turnover; their chromosomal distribution depends on local contexts
      (neighboring core genes), and content in mobile genetic elements. Hotspots
      concentrate most changes in gene repertoires, reduce the trade-off between genome
      diversification and organization, and should be treasure troves of strain
      specific adaptive genes. Most mobile genetic elements and antibiotic resistance
      genes are in hotspots, but many hotspots lack recognizable mobile genetic
      elements and exhibit frequent homologous recombination at flanking core genes.
      Overrepresentation of hotspots with fewer mobile genetic elements in naturally
      transformable bacteria suggests that homologous recombination and horizontal gene
      transfer are tightly linked in genome evolution.Horizontal gene transfer (HGT) is
      an important mechanism for genome evolution and adaptation in bacteria. Here,
      Oliveira and colleagues find HGT hotspots comprising  ~ 1% of the chromosomal
      regions in 80 bacterial species.

PMID- 29018199
TI  - Pan-Antarctic analysis aggregating spatial estimates of Adelie penguin abundance
      reveals robust dynamics despite stochastic noise.
AB  - Colonially-breeding seabirds have long served as indicator species for the health
      of the oceans on which they depend. Abundance and breeding data are repeatedly
      collected at fixed study sites in the hopes that changes in abundance and
      productivity may be useful for adaptive management of marine resources, but their
      suitability for this purpose is often unknown. To address this, we fit a Bayesian
      population dynamics model that includes process and observation error to all
      known Adelie penguin abundance data (1982-2015) in the Antarctic, covering >95%
      of their population globally. We find that process error exceeds observation
      error in this system, and that continent-wide "year effects" strongly influence
      population growth rates. Our findings have important implications for the use of
      Adelie penguins in Southern Ocean feedback management, and suggest that
      aggregating abundance across space provides the fastest reliable signal of true
      population change for species whose dynamics are driven by stochastic
      processes.Adelie penguins are a key Antarctic indicator species, but data
      patchiness has challenged efforts to link population dynamics to key drivers. Che
      Castaldo et al. resolve this issue using a pan-Antarctic Bayesian model to infer
      missing data, and show that spatial aggregation leads to more robust inference
      regarding dynamics.

PMID- 29018200
TI  - Direction-specific interaction forces underlying zinc oxide crystal growth by
      oriented attachment.
AB  - Crystallization by particle attachment is impacting our understanding of natural
      mineralization processes and holds promise for novel materials design. When
      particles assemble in crystallographic alignment, expulsion of the intervening
      solvent and particle coalescence are enabled by near-perfect co-alignment via
      interparticle forces that remain poorly quantified. Here we report measurement
      and simulation of these nanoscale aligning forces for the ZnO(0001)
      ZnO(000[Formula: see text]) system in aqueous solution. Dynamic force
      spectroscopy using nanoengineered single crystal probes reveals an attractive
      force with 60o rotational periodicity. Calculated distance and orientation
      dependent potentials of mean force show several attractive free energy wells
      distinguished by numbers of intervening water layers, which reach a minimum when
      aligned. The calculated activation energy to separate the attractively bound
      solvated interfaces perfectly reproduces the measured 60o periodicity, revealing
      the key role of intervening water structuring as a basis to generate the
      interparticle torque that completes alignment and enables coalescence.Crystal
      growth is a fundamental process, important in a wide range of fields, but the
      interparticle forces responsible for molecule alignment are not well understood.
      Here, the authors measure the alignment forces in ZnO using dynamic force
      spectroscopy, highlighting the role of intervening water molecules.

PMID- 29018202
TI  - Erratum: Symmetry-based indicators of band topology in the 230 space groups.
AB  - A correction to this article has been published and is linked from the HTML
      version of this article.

PMID- 29018203
TI  - Nonvolatile nuclear spin memory enables sensor-unlimited nanoscale spectroscopy
      of small spin clusters.
AB  - In nanoscale metrology, dissipation of the sensor limits its performance. Strong
      dissipation has a negative impact on sensitivity, and sensor-target interaction
      even causes relaxation or dephasing of the latter. The weak dissipation of
      nitrogen-vacancy (NV) sensors in room temperature diamond enables detection of
      individual target nuclear spins, yet limits the spectral resolution of nuclear
      magnetic resonance (NMR) spectroscopy to several hundred Hertz, which typically
      prevents molecular recognition. Here, we use the NV intrinsic nuclear spin as a
      nonvolatile classical memory to store NMR information, while suppressing sensor
      back-action on the target using controlled decoupling of sensor, memory, and
      target. We demonstrate memory lifetimes up to 4 min and apply measurement and
      decoupling protocols, which exploit such memories efficiently. Our universal NV
      based sensor device records single-spin NMR spectra with 13 Hz resolution at room
      temperature.Dissipation of the sensor is a limiting factor in metrology. Here,
      Pfender et al. suppress this effect employing the nuclear spin of an NV centre
      for robust intermediate storage of classical NMR information, allowing then to
      record single-spin NMR spectra with 13 Hz resolution at room temperature.

PMID- 29018201
TI  - Activating de novo mutations in NFE2L2 encoding NRF2 cause a multisystem
      disorder.
AB  - Transcription factor NRF2, encoded by NFE2L2, is the master regulator of defense
      against stress in mammalian cells. Somatic mutations of NFE2L2 leading to NRF2
      accumulation promote cell survival and drug resistance in cancer cells. Here we
      show that the same mutations as inborn de novo mutations cause an early onset
      multisystem disorder with failure to thrive, immunodeficiency and neurological
      symptoms. NRF2 accumulation leads to widespread misregulation of gene expression
      and an imbalance in cytosolic redox balance. The unique combination of white
      matter lesions, hypohomocysteinaemia and increased G-6-P-dehydrogenase activity
      will facilitate early diagnosis and therapeutic intervention of this novel
      disorder.The NRF2 transcription factor regulates the response to stress in
      mammalian cells. Here, the authors show that activating mutations in NRF2,
      commonly found in cancer cells, are found in four patients with a multisystem
      disorder characterized by immunodeficiency and neurological symptoms.

PMID- 29018204
TI  - A new stress sensor and risk factor for suicide: the T allele of the functional
      genetic variant in the GABRA6 gene.
AB  - Low GABA transmission has been reported in suicide, and GABRA6 rs3219151 T allele
      has been associated with greater physiological and endocrine stress response in
      previous studies. Although environmental stress also plays a role in suicide, the
      possible role of this allele has not been investigated in this respect. In our
      present study effect of rs3219151 of GABRA6 gene in interaction with recent
      negative life events on lifetime and current depression, current anxiety, as well
      as lifetime suicide were investigated using regression models in a white European
      general sample of 2283 subjects. Post hoc measures for phenotypes related to
      suicide risk were also tested for association with rs3219151 in interaction with
      environmental stress. No main effect of the GABRA6 rs3219151 was detected, but in
      those exposed to recent negative life events GABRA6 T allele increased current
      anxiety and depression as well as specific elements of suicide risk including
      suicidal and death-related thoughts, hopelessness, restlessness and agitation,
      insomnia and impulsiveness as measured by the STOP task. Our data indicate that
      stress-associated suicide risk is elevated in carriers of the GABRA6 rs3219151 T
      allele with several independent markers and predictors of suicidal behaviours
      converging to this increased risk.

PMID- 29018205
TI  - Genetic status of KRAS modulates the role of Neuropilin-1 in tumorigenesis.
AB  - Neuropilin-1 (NRP1), a non-tyrosine kinase receptor, is overexpressed in many
      cancers including pancreatic and lung cancers. Inhibition of NRP1 expression,
      however, has differing pro-tumor vs. anti-tumor effects, depending on the cancer
      types. To understand the differential role of NRP1 in tumorigenesis process, we
      utilized cells from two different cancer types, pancreatic and lung, each
      containing either wild type KRAS (KRAS wt) or mutant KRAS (KRAS mt). Inhibition
      of NRP1 expression by shRNA in both pancreatic and lung cancer cells containing
      dominant active KRAS mt caused increased cell viability and tumor growth. On the
      contrary, inhibition of NRP1, in the tumor cells containing KRAS wt showed
      decreased tumor growth. Importantly, concurrent inhibition of KRAS mt and NRP1 in
      the tumor cells reverses the increased viability and leads to tumor inhibition.
      We found that NRP1 shRNA expressing KRAS mt tumor cells caused increased cell
      viability by decreasing SMAD2 phosphorylation. Our findings demonstrate that the
      effects of NRP1 knockdown in cancer cells are dependent on the genetic status of
      KRAS.

PMID- 29018206
TI  - Tumor-Penetrating Delivery of siRNA against TNFalpha to Human Vestibular
      Schwannomas.
AB  - Vestibular schwannoma (VS) is the most common tumor of the cerebellopontine
      angle, and it typically presents with sensorineural hearing loss. The genomic
      landscape of schwannoma is complex and many of the molecules implicated in VS
      pathogenesis represent targets not amenable to antibody-based or small molecule
      therapeutics. Tumor-targeted delivery of small interfering RNA (siRNA)
      therapeutics provides a direct and effective means to interrogate targets while
      minimizing off-target effects. To establish a preclinical model for therapeutic
      inhibition of putative targets in VS, archived tumor specimens, fresh tumor cells
      derived from patients with sporadic VS, and an established schwannoma cell line
      were screened. Nanoparticles directed by the tumor-homing peptide iRGD were
      selectively taken up by primary VS cultures in vitro via interactions with
      alphavbeta3/beta5 integrins and neuropilin-1 (NRP-1). Cellular uptake was
      inhibited by a neutralizing antibody against alphav integrin in a dose-dependent
      manner. When applied to primary VS cultures, iRGD-targeted nanoparticles
      delivered siRNA directed against TNFalpha in a receptor-specific fashion to
      potently silence gene expression and protein secretion. Taken together, our
      results provide a proof of principle for tumor-targeted, nanoparticle-mediated
      delivery of siRNA to VS and establish a novel platform for the development and
      pre-clinical screening of molecular therapeutics against VS.

PMID- 29018209
TI  - Erratum: miR-15a/miR-16 down-regulates BMI1, impacting Ub-H2A mediated DNA repair
      and breast cancer cell sensitivity to doxorubicin.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29018207
TI  - Stress-induced plasticity of dynamic collagen networks.
AB  - The structure and mechanics of tissues is constantly perturbed by endogenous
      forces originated from cells, and at the same time regulate many important
      cellular functions such as migration, differentiation, and growth. Here we show
      that 3D collagen gels, major components of connective tissues and extracellular
      matrix (ECM), are significantly and irreversibly remodeled by cellular traction
      forces, as well as by macroscopic strains. To understand this ECM plasticity, we
      develop a computational model that takes into account the sliding and merging of
      ECM fibers. We have confirmed the model predictions with experiment. Our results
      suggest the profound impacts of cellular traction forces on their host ECM during
      development and cancer progression, and suggest indirect mechanical channels of
      cell-cell communications in 3D fibrous matrices.The structure and mechanics of
      tissues is constantly perturbed by endogenous forces originated from cells. Here
      the authors show that 3D collagen gels, major components of connective tissues
      and extracellular matrix, are significantly and irreversibly remodelled by
      cellular traction forces and by macroscopic strains.

PMID- 29018208
TI  - Difference in intracellular temperature rise between matured and precursor brown
      adipocytes in response to uncoupler and beta-adrenergic agonist stimuli.
AB  - Brown adipocytes function to maintain body temperature by heat production.
      However, direct measurement of heat production at a single cell level remains
      difficult. Here we developed a method to measure the temperature within primary
      cultured brown adipocytes using a cationic fluorescent polymeric thermometer.
      Placement of the thermometer within a matured brown adipocyte and a precursor
      cell enabled the detection of heat production following uncoupler treatment. The
      increase in the intracellular temperature due to stimulation with a mitochondrial
      uncoupler was higher in matured brown adipocytes than in precursor cells.
      Stimulation with a beta-adrenergic receptor (beta-AR) agonist, norepinephrine,
      raised the intracellular temperature of matured brown adipocytes to a level
      comparable to that observed after stimulation with a beta3-AR-specific agonist,
      CL316.243. In contrast, neither beta-AR agonist induced an intracellular
      temperature increase in precursor cells. Further, pretreatment of brown
      adipocytes with a beta3-AR antagonist inhibited the norepinephrine-stimulated
      elevation of temperature. These results demonstrate that our novel method
      successfully determined the difference in intracellular temperature increase
      between matured brown adipocytes and precursor cells in response to stimulation
      by an uncoupler and beta-AR agonists.

PMID- 29018211
TI  - An exact solution for the free-vibration analysis of functionally graded carbon
      nanotube-reinforced composite beams with arbitrary boundary conditions.
AB  - We present an exact method to model the free vibration of functionally graded
      carbon-nanotube-reinforced composite (FG-CNTRC) beams with arbitrary boundary
      conditions based on first-order shear deformation elasticity theory. Five types
      of carbon nanotube (CNT) distributions are considered. The distributions are
      either uniform or functionally graded and are assumed to be continuous through
      the thickness of the beams. The displacements and rotational components of the
      beams are expressed as a linear combination of the standard Fourier series and
      several supplementary functions. The formulation is derived using the modified
      Fourier series and solved using the strong-form solution and the weak-form
      solution (i.e., the Rayleigh-Ritz method). Both solutions are applicable to
      various combinations of boundary constraints, including classical boundary
      conditions and elastic-supported boundary conditions. The accuracy, efficiency
      and validity of the two solutions presented are demonstrated via comparison with
      published results. A parametric study is conducted on the influence of several
      key parameters, namely, the L/h ratio, CNT volume fraction, CNT distribution,
      boundary spring stiffness and shear correction factor, on the free vibration of
      FG-CNTRC beams.

PMID- 29018210
TI  - Magnetic Nanoparticle-Reduced Graphene Oxide Nanocomposite as a Novel
      Bioelectrode for Mediatorless-Membraneless Glucose Enzymatic Biofuel Cells.
AB  - In this work, an enzymatic biofuel cell (EBC) based on a membraneless and
      mediatorless glucose enzymatic fuel cell system was constructed for operation in
      physiological conditions (pH 7.0 and temperature 37  degrees C). The new platform
      EBC made of nanocomposite, including magnetic nanoparticles (Fe3O4 NPs) and
      reduced graphene oxide (RGO), was used for the immobilization of glucose oxidase
      (GOD) as bioanode and bilirubin oxidase (BOD) as biocathode. The EBC
      bioelectrodes were fabricated without binder or adhesive agents for immobilized
      enzyme and the first EBC using superparamagnetic properties with Fe3O4 NPs has
      been reported. The performance of the EBC was evaluated with promising results.
      In EBC tests, the maximum power density of the EBC was 73.7 MUW cm-2 and an open
      circuit voltage (OCV) as +0.63 V with 5 mM of glucose concentration for the
      physiological condition of humans. The Fe3O4-RGO nanocomposite offers remarkable
      enhancement in large surface areas, is a favorable environment for enzyme
      immobilization, and facilitates electron transfer between enzymes and electrode
      surfaces. Fe3O4 and RGO have been implied as new promising composite
      nanomaterials for immobilizing enzymes and efficient platforms due to their
      superparamagnetism properties. Thus, glucose EBCs could potentially be used as
      self-powered biosensors or electric power sources for biomedical device
      applications.

PMID- 29018212
TI  - Enhanced Therapeutic Treatment of Colorectal Cancer Using Surface-Modified
      Nanoporous Acupuncture Needles.
AB  - Acupuncture originated within the auspices of Oriental medicine, and today is
      used as an alternative method for treating various diseases and symptoms. The
      physiological mechanisms of acupuncture appear to involve the release of
      endogenous opiates and neurotransmitters, with the signals mediating through
      electrical stimulation of the central nervous system (CNS). Earlier we reported a
      nanoporous stainless steel acupuncture needle with enhanced therapeutic
      properties, evaluated by electrophysiological and behavioral responses in Sprague
      Dawley (SD) rats. Herein, we investigate molecular changes in colorectal cancer
      (CRC) rats by acupuncture treatment using the nanoporous needles. Treatment at
      acupoint HT7 is found most effective at reducing average tumor size, beta-catenin
      expression levels, and the number of aberrant crypt foci in the colon
      endothelium. Surface modification of acupuncture needles further enhances the
      therapeutic effects of acupuncture treatment in CRC rats.

PMID- 29018214
TI  - Correspondence: Reply to 'Numerical modelling of the PERM anomaly and the
      Emeishan large igneous province'.

PMID- 29018213
TI  - Strict molecular sieving over electrodeposited 2D-interspacing-narrowed graphene
      oxide membranes.
AB  - To separate small molecules/species, it's crucial but still challenging to narrow
      the 2D-interspacing of graphene oxide (GO) membranes without damaging the
      membrane. Here the fast deposition of ultrathin, defect-free and robust GO layers
      is realized on porous stainless steel hollow fibers (PSSHFs) by a facile and
      practical electrophoresis deposition (ED) method. In this approach, oxygen
      containing groups of GO are selectively reduced, leading to a controlled decrease
      of the 2D channels of stacked GO layers. The resultant ED-GO@PSSHF composite
      membranes featured a sharp cutoff between C2 (ethane and ethene) and C3 (propane
      and propene) hydrocarbons and exhibited nearly complete rejections for the
      smallest alcohol and ion in aqueous solutions. This demonstrates the versatility
      of GO based membranes for the precise separation of various types of mixtures. At
      the same time, a robust mechanical strength of the ED-GO@PSSHF membrane is also
      achieved due to the enhanced interaction at GO/support and GO/GO
      interfaces.Producing graphene oxide membranes with narrow channels is desirable
      for small molecule separations, but methods to narrow the 2D spacing typically
      result in membrane damage. Here the authors exploit electrophoresis-deposition to
      prepare GO membranes that are reduced in situ, leading to narrow and uniform 2D
      channels.

PMID- 29018215
TI  - Impact of Infectious Disease Consultation on Clinical Management and Outcome of
      Patients with Bloodstream Infection: a Retrospective Cohort Study.
AB  - The impact of consultation by infectious diseases (ID) physicians on management
      and outcomes of patients has not been determined in China. We assembled a
      retrospective cohort of 995 consecutive adult cases with bloodstream infections
      (BSI) in a major teaching hospital in China. Survival analysis was performed with
      Cox regression and the Kaplan-Meier curves. Among the 995 patients with BSI, 421
      (42.3%) received consultation by ID physicians and 574 (57.7%) did not. ID
      consultation led to a significant lower hazard of death (hazard ratio [HR],
      0.575; P < 0.05) and more appropriate antimicrobial use (95.0% vs 67.6%, P <
      0.05). ID consultation was a protective factor among patients with BSI due to
      Gram-positive (HR, 0.551; P < 0.05) or Gram-negative (HR, 0.331; P < 0.05)
      bacteria. Multiple ID consultation was a protective factor (HR, 0.51; P < 0.05),
      while single consultation was not. In conclusion, ID consultation led to
      significant lower risk for patients with BSI and improved management. Multiple
      rather than single ID consultations reduced the hazard of death.

PMID- 29018217
TI  - Quantifying Anthropogenic Stress on Groundwater Resources.
AB  - This study explores a general framework for quantifying anthropogenic influences
      on groundwater budget based on normalized human outflow (hout) and inflow (hin).
      The framework is useful for sustainability assessment of groundwater systems and
      allows investigating the effects of different human water abstraction scenarios
      on the overall aquifer regime (e.g., depleted, natural flow-dominated, and human
      flow-dominated). We apply this approach to selected regions in the USA, Germany
      and Iran to evaluate the current aquifer regime. We subsequently present two
      scenarios of changes in human water withdrawals and return flow to the system
      (individually and combined). Results show that approximately one-third of the
      selected aquifers in the USA, and half of the selected aquifers in Iran are
      dominated by human activities, while the selected aquifers in Germany are natural
      flow-dominated. The scenario analysis results also show that reduced human
      withdrawals could help with regime change in some aquifers. For instance, in two
      of the selected USA aquifers, a decrease in anthropogenic influences by ~20% may
      change the condition of depleted regime to natural flow-dominated regime. We
      specifically highlight a trending threat to the sustainability of groundwater in
      northwest Iran and California, and the need for more careful assessment and
      monitoring practices as well as strict regulations to mitigate the negative
      impacts of groundwater overexploitation.

PMID- 29018216
TI  - Structural and mechanistic characterization of an archaeal-like chaperonin from a
      thermophilic bacterium.
AB  - The chaperonins (CPNs) are megadalton sized hollow complexes with two cavities
      that open and close to encapsulate non-native proteins. CPNs are assigned to two
      sequence-related groups that have distinct allosteric mechanisms. In Group I CPNs
      a detachable co-chaperone, GroES, closes the chambers whereas in Group II a built
      in lid closes the chambers. Group I CPNs have a bacterial ancestry, whereas Group
      II CPNs are archaeal in origin. Here we describe open and closed crystal
      structures representing a new phylogenetic branch of CPNs. These Group III CPNs
      are divergent in sequence and structure from extant CPNs, but are closed by a
      built-in lid like Group II CPNs. A nucleotide-sensing loop, present in both Group
      I and Group II CPNs, is notably absent. We identified inter-ring pivot joints
      that articulate during ring closure. These Group III CPNs likely represent a
      relic from the ancestral CPN that formed distinct bacterial and archaeal
      branches.Chaperonins (CPNs) are ATP-dependent protein-folding machines. Here the
      authors present the open and closed crystal structures of a Group III CPN from
      the thermophilic bacterium Carboxydothermus hydrogenoformans, discuss its
      mechanism and structurally compare it with Group I and II CPNs.

PMID- 29018218
TI  - Associative visual learning by tethered bees in a controlled visual environment.
AB  - Free-flying honeybees exhibit remarkable cognitive capacities but the neural
      underpinnings of these capacities cannot be studied in flying insects.
      Conversely, immobilized bees are accessible to neurobiological investigation but
      display poor visual learning. To overcome this limitation, we aimed at
      establishing a controlled visual environment in which tethered bees walking on a
      spherical treadmill learn to discriminate visual stimuli video projected in front
      of them. Freely flying bees trained to walk into a miniature Y-maze displaying
      these stimuli in a dark environment learned the visual discrimination efficiently
      when one of them (CS+) was paired with sucrose and the other with quinine
      solution (CS-). Adapting this discrimination to the treadmill paradigm with a
      tethered, walking bee was successful as bees exhibited robust discrimination and
      preferred the CS+ to the CS- after training. As learning was better in the maze,
      movement freedom, active vision and behavioral context might be important for
      visual learning. The nature of the punishment associated with the CS- also
      affects learning as quinine and distilled water enhanced the proportion of
      learners. Thus, visual learning is amenable to a controlled environment in which
      tethered bees learn visual stimuli, a result that is important for future
      neurobiological studies in virtual reality.

PMID- 29018219
TI  - Spatially restricted loading of BRD2 at DNA double-strand breaks protects H4
      acetylation domains and promotes DNA repair.
AB  - The n-terminal tail of histone H4 recruits repair proteins, including 53BP1, to
      DNA double-strand breaks (DSB) and undergoes dynamic acetylation during DSB
      repair. However, how H4 acetylation (H4Ac) recruits repair proteins and
      reorganizes chromatin during DNA repair is unclear. Here, we show that the
      bromodomain protein BRD2 is recruited to DSBs. This recruitment requires binding
      of BRD2's tandem bromodomains to H4Ac, which is generated at DSBs by the
      Tip60/KAT5 acetyltransferase. Binding of BRD2 to H4Ac protects the underlying
      acetylated chromatin from attack by histone deacetylases and allows acetylation
      to spread along the flanking chromatin. However, BRD2 recruitment is spatially
      restricted to a chromatin domain extending only 2 kb either side of the DSB, and
      BRD2 does not spread into the chromatin domains flanking the break. Instead, BRD2
      facilitates recruitment of a second bromodomain protein, ZMYND8, which spreads
      along the flanking chromatin, but is excluded from the DSB region. This creates a
      spatially restricted H4Ac/BRD2 domain which reorganizes chromatin at DSBs, limits
      binding of the L3MBTL1 repressor and promotes 53BP1 binding, while limiting end
      resection of DSBs. BRD2 therefore creates a restricted chromatin environment
      surrounding DSBs which facilitates DSB repair and which is framed by extensive
      ZMYND8 domains on the flanking chromatin.

PMID- 29018220
TI  - Variant surface glycoprotein density defines an immune evasion threshold for
      African trypanosomes undergoing antigenic variation.
AB  - Trypanosoma brucei is a protozoan parasite that evades its host's adaptive immune
      response by repeatedly replacing its dense variant surface glycoprotein (VSG)
      coat from its large genomic VSG repertoire. While the mechanisms regulating VSG
      gene expression and diversification have been examined extensively, the dynamics
      of VSG coat replacement at the protein level, and the impact of this process on
      successful immune evasion, remain unclear. Here we evaluate the rate of VSG
      replacement at the trypanosome surface following a genetic VSG switch, and show
      that full coat replacement requires several days to complete. Using in vivo
      infection assays, we demonstrate that parasites undergoing coat replacement are
      only vulnerable to clearance via early IgM antibodies for a limited time.
      Finally, we show that IgM loses its ability to mediate trypanosome clearance at
      unexpectedly early stages of coat replacement based on a critical density
      threshold of its cognate VSGs on the parasite surface. Trypanosoma brucei evades
      the host immune system through replacement of a variant surface glycoprotein
      (VSG) coat. Here, the authors show that VSG replacement takes several days to
      complete, and the parasite is vulnerable to the host immune system for a short
      period of time during the process.

PMID- 29018221
TI  - Temporal dynamics of the mimetic allele frequency at the doublesex locus, which
      controls polymorphic Batesian mimicry in Papilio memnon butterflies.
AB  - Tracking allele frequencies is essential for understanding how polymorphisms of
      adaptive traits are maintained. In Papilio memnon butterflies, which exhibit a
      female-limited Batesian mimicry polymorphism (wing-pattern polymorphism), two
      alleles at the doublesex (dsx) locus correspond to mimetic and non-mimetic forms
      in females; males carry both dsx alleles but display only the non-mimetic form.
      This polymorphism is thought to be maintained by a negative frequency-dependent
      selection. By tracking dsx allele frequencies in both sexes at a Taiwanese site
      over four years, we found that the mimetic allele persists at intermediate
      frequencies even when the unpalatable model papilionid butterflies (Pachliopta
      and Atrophaneura species) were very rare or absent. The rates of male mate choice
      did not differ between the two female forms; neither did insemination number nor
      age composition, suggesting equivalent reproductive performance of the two forms
      over time. Our results characterised the temporal dynamics of the mimetic allele
      frequency in the field for the first time and give insights into underlying
      processes involved in the persistence of the female-limited Batesian mimicry
      polymorphism.

PMID- 29018222
TI  - Spatial-temporal distribution of dengue and climate characteristics for two
      clusters in Sri Lanka from 2012 to 2016.
AB  - Dengue is a vector-borne disease causing high morbidity and mortality in tropical
      and subtropical countries. Urbanization, globalization, and lack of effective
      mosquito control have lead to dramatically increased frequency and magnitude of
      dengue epidemic in the past 40 years. The virus and the mosquito vectors keep
      expanding geographically in the tropical regions of the world. Using the hot spot
      analysis and the spatial-temporal clustering method, we investigated the spatial
      temporal distribution of dengue in Sri Lanka from 2012 to 2016 to identify
      spatial-temporal clusters and elucidate the association of climatic factors with
      dengue incidence. We detected two important spatial-temporal clusters in Sri
      Lanka. Dengue incidences were predicted by combining historical dengue incidence
      data with climate data, and hot and cold spots were forecasted using the
      predicted dengue incidences to identify areas at high risks. Targeting the hot
      spots during outbreaks instead of all the regions can save resources and time for
      public health authorities. Our study helps better understand how climatic factors
      impact spatial and temporal spread of dengue virus. Hot spot prediction helps
      public health authorities forecast future high risk areas and direct control
      measures to minimize cost on health, time, and economy.

PMID- 29018223
TI  - Mechanistic Evaluation and Translational Signature of Gemcitabine-induced
      Chemoresistance by Quantitative Phosphoproteomics Analysis with iTRAQ Labeling
      Mass Spectrometry.
AB  - One of the main causations of the poor prognosis of pancreatic cancer is the lack
      of effective chemotherapies. Gemcitabine is a widely used chemotherapeutic drug,
      but limited therapeutic efficacy is achieved due to chemoresistance. Recent
      studies demonstrated that the presence of cancer stem cells may lead to the
      failure of chemotherapy. Moreover, gemcitabine can promote the stemness of
      pancreatic cancer cells. We detected the alterations in protein phosphorylation
      and signaling pathways in pancreatic cancer cells after gemcitabine treatment
      using iTRAQ labeling LC-MS/MS, because it was featured with the advantages of
      strong separation ability and analysis range. A total of 232 differentially
      expressed phosphorylated proteins were identified in this study. Gene Ontology
      analysis revealed that nuclear lumen, nuclear part and organelle lumen were
      enriched for cell components and protein binding, poly (A) RNA binding and RNA
      binding were enriched for molecular function. A variety of signaling pathways
      were enriched based on KEGG analysis. AMPK, mTOR and PI3K/Akt pathways were
      verified after gemcitabine exposure. Moreover, we found there were complex
      interactions of phosphorylated proteins in modulating cancer stemness induced by
      gemcitabine exposure based on PPIs map. Our experiments may identify potential
      targets and strategies for sensitizing pancreatic cancer cells to gemcitabine.

PMID- 29018224
TI  - Integrative analysis of genomic and epigenomic regulation of the transcriptome in
      liver cancer.
AB  - Hepatocellular carcinoma harbors numerous genomic and epigenomic aberrations of
      DNA copy numbers and DNA methylation. Transcriptomic deregulation by these
      aberrations plays key driver roles in heterogeneous progression of cancers. Here,
      we profile DNA copy numbers, DNA methylation, and messenger RNA expression levels
      from 64 cases of hepatocellular carcinoma specimens. We find that the frequencies
      of the aberrancies of the DNA copy-number-correlated (CNVcor) expression genes
      and the methylation-correlated expression (METcor) genes are co-regulated
      significantly. Multi-omics integration of the CNVcor and METcor genes reveal
      three prognostic subtypes of hepatocellular carcinoma, which can be validated by
      an independent data. The most aggressive subtype expressing stemness genes has
      frequent BAP1 mutations, implying its pivotal role in the aggressive tumor
      progression. In conclusion, our integrative analysis of genomic and epigenomic
      regulation provides new insights on the multi-layered pathobiology of
      hepatocellular carcinoma, which might be helpful in developing precision
      management for hepatocellular carcinoma patients.Hepatocellular carcinoma is
      known to harbour numerous genomic and epigenomic aberrations, driving
      transcriptomic deregulation. Here, the authors integrate genomic, epigenomic, and
      expression data to reveal three prognostic subtypes, providing insight to the
      pathobiology of hepatocellular carcinoma.

PMID- 29018225
TI  - S1P1 deletion differentially affects TH17 and Regulatory T cells.
AB  - Sphingosine-1 phosphate receptor 1 (S1P1) is critical for the egress of T and B
      cells out of lymphoid organs. Although S1P1 agonist fingolimod is currently used
      for the treatment of multiple sclerosis (MS) little is known how S1P1 signaling
      regulates Th17 and Treg cell homeostasis. To study the impact of S1P1 signaling
      on Th17 and Treg cell biology, we specifically deleted S1P1 in Th17 and Treg
      cells using IL-17A Cre and Foxp3 Cre mice, respectively. Deletion of S1P1 in Th17
      cells conferred resistance to experimental autoimmune encephalomyelitis (EAE). On
      the other hand, permanent deletion of S1P1 in Treg cells resulted in autoimmunity
      and acute deletion rendered mice more susceptible to EAE. Importantly, our study
      revealed that S1P1 not only regulated the egress of Treg cells out of lymphoid
      organs and subsequent non-lymphoid tissue distribution but also their phenotypic
      diversity. Most of the Treg cells found in S1P1-deficient mice as well as MS
      patients on fingolimod therapy had an activated phenotype and were more prone to
      apoptosis, thus converted to effector Treg. Our results provide novel insight
      into the functions of S1P1 and potential impact of long term fingolimod use on
      Th17 and Treg cell biology and general health in MS patients.

PMID- 29018226
TI  - Atmospheric observations show accurate reporting and little growth in India's
      methane emissions.
AB  - Changes in tropical wetland, ruminant or rice emissions are thought to have
      played a role in recent variations in atmospheric methane (CH4) concentrations.
      India has the world's largest ruminant population and produces ~ 20% of the
      world's rice. Therefore, changes in these sources could have significant
      implications for global warming. Here, we infer India's CH4 emissions for the
      period 2010-2015 using a combination of satellite, surface and aircraft data. We
      apply a high-resolution atmospheric transport model to simulate data from these
      platforms to infer fluxes at sub-national scales and to quantify changes in rice
      emissions. We find that average emissions over this period are 22.0 (19.6-24.3)
      Tg yr-1, which is consistent with the emissions reported by India to the United
      Framework Convention on Climate Change. Annual emissions have not changed
      significantly (0.2 +/- 0.7 Tg yr-1) between 2010 and 2015, suggesting that major
      CH4 sources did not change appreciably. These findings are in contrast to another
      major economy, China, which has shown significant growth in recent years due to
      increasing fossil fuel emissions. However, the trend in a global emission
      inventory has been overestimated for China due to incorrect rate of fossil fuel
      growth. Here, we find growth has been overestimated in India but likely due to
      ruminant and waste sectors.India's methane emissions have been quantified using
      atmospheric measurements to provide an independent comparison with reported
      emissions. Here Ganesan et al. find that derived methane emissions are consistent
      with India's reports and no significant trend has been observed between 2010
      2015.

PMID- 29018227
TI  - The human blood parasite Schistosoma mansoni expresses extracellular tegumental
      calpains that cleave the blood clotting protein fibronectin.
AB  - Schistosomes are intravascular, parasitic flatworms that cause debilitating
      disease afflicting >200 million people. Proteins expressed at the host-parasite
      interface likely play key roles in modifying the worm's local environment to
      ensure parasite survival. Proteomic analysis reveals that two proteases belonging
      to the calpain family (SmCalp1 and SmCalp2) are expressed in the Schistosoma
      mansoni tegument. We have cloned both; while highly conserved in domain
      organization they display just 31% amino acid sequence identity. Both display
      high relative expression in the parasite's intravascular life forms.
      Immunolocalization and activity based protein profiling experiments confirm the
      presence of the enzymes at the host-parasite interface. Living parasites exhibit
      surface calpain activity that is blocked in the absence of calcium and in the
      presence of calpain inhibitors (E64c, PD 150606 and calpastatin). While calpains
      are invariably reported to be exclusively intracellular (except in diseased or
      injured tissues), our data show that schistosomes display unique, constitutive,
      functional extracellular calpain activity. Furthermore we show that the worms are
      capable of cleaving the host blood clotting protein fibronectin and that this
      activity can be inhibited by E64c. We hypothesize that SmCalp1 and/or SmCalp2
      perform this cleavage function to impede blood clot formation around the worms in
      vivo.

PMID- 29018228
TI  - Charge and Lattice Fluctuations in Molecule-Based Spin Liquids.
AB  - Spin liquid (SL) systems have been the subject of much attention recently, as
      they have been theoretically predicted to not freeze, even at 0 K. Despite
      extensive searches being made for such a system, only a few candidates have been
      found. All of these candidates share geometrical frustrations that are based on
      triangular lattices. We applied vibrational spectroscopy to one of the candidates
      of a molecule-based SL system, and we compared its results against three
      antiferromagnetic compounds and four charge-ordered compounds. All of their
      structural motifs belong to triangular lattices. The C=C stretching modes in the
      SL state indicated that there were charge and lattice fluctuations. These
      fluctuations were suppressed but non-negligible in the AF compounds. This finding
      is potentially significant, as it indicates that a hidden lattice and charge
      fluctuation are the driving force of a geometrical frustration, which eventually
      leads to a SL state.

PMID- 29018229
TI  - Improving extinction projections across scales and habitats using the countryside
      species-area relationship.
AB  - The species-area relationship (SAR) has been often used to project species
      extinctions as a consequence of habitat loss. However, recent studies have
      suggested that the SAR may overestimate species extinctions, at least in the
      short-term. We argue that the main reason for this overestimation is that the
      classic SAR ignores the persistence of species in human-modified habitats. We use
      data collected worldwide to analyse what is the fraction of bird and plant
      species that remain in different human-modified habitats at the local scale after
      full habitat conversion. We observe that both taxa have consistent responses to
      the different land-use types, with strongest reductions in species richness in
      cropland across the globe, and in pasture in the tropics. We show that the
      results from these studies cannot be linearly scaled from plots to large regions,
      as this again overestimates the impacts of land-use change on biodiversity. The
      countryside SAR provides a unifying framework to incorporate both the effect of
      species persistence in the landscape matrix and the non-linear response of the
      proportion of species extinctions to sampling area, generating more realistic
      projections of biodiversity loss.

PMID- 29018230
TI  - Affective Touch Enhances Self-Face Recognition During Multisensory Integration.
AB  - Multisensory integration is a powerful mechanism for constructing body awareness
      and key for the sense of selfhood. Recent evidence has shown that the specialised
      C tactile modality that gives rise to feelings of pleasant, affective touch, can
      enhance the experience of body ownership during multisensory integration.
      Nevertheless, no study has examined whether affective touch can also modulate
      psychological identification with our face, the hallmark of our identity. The
      current study used the enfacement illusion paradigm to investigate the role of
      affective touch in the modulation of self-face recognition during multisensory
      integration. In the first experiment (N = 30), healthy participants were stroked
      on the cheek while they were looking at another face being stroked on the cheek
      in synchrony or asynchrony with affective (slow; CT-optimal) vs. neutral (fast;
      CT-suboptimal) touch. In the second experiment (N = 38) spatial incongruence of
      touch (cheek vs. forehead) was used as a control condition instead of temporal
      asynchrony. Overall, our data suggest that CT-optimal, affective touch enhances
      subjective (but not behavioural) self-face recognition during synchronous and
      spatially congruent integration of different sensations and possibly reduces
      deafference during asynchronous multisensory integration. We discuss the role of
      affective touch in shaping the more social aspects of our self.

PMID- 29018231
TI  - Biochemical mechanisms of dose-dependent cytotoxicity and ROS-mediated apoptosis
      induced by lead sulfide/graphene oxide quantum dots for potential bioimaging
      applications.
AB  - Colloidal quantum dots (CQD) have attracted considerable attention for biomedical
      diagnosis and imaging as well as biochemical analysis and stem cell tracking. In
      this study, quasi core/shell lead sulfide/reduced graphene oxide CQD with near
      infrared emission (1100 nm) were prepared for potential bioimaging applications.
      The nanocrystals had an average diameter of ~4 nm, a hydrodynamic size of ~8 nm,
      and a high quantum efficiency of 28%. Toxicity assay of the hybrid CQD in the
      cultured human mononuclear blood cells does not show cytotoxicity up to 200
      ug/ml. At high concentrations, damage to mitochondrial activity and mitochondrial
      membrane potential (MMP) due to the formation of uncontrollable amounts of
      intracellular oxygen radicals (ROS) was observed. Cell membrane and Lysosome
      damage or a transition in mitochondrial permeability were also noticed.
      Understanding of cell-nanoparticle interaction at the molecular level is useful
      for the development of new fluorophores for biomedical imaging.

PMID- 29018232
TI  - High Reflectance Nanoscale V/Sc Multilayer for Soft X-ray Water Window Region.
AB  - V/Sc multilayer is experimentally demonstrated for the first time as a high
      reflectance mirror for the soft X-ray water window region. It primarily works at
      above the Sc-L edge (lambda = 3.11 nm) under near normal incidence while a second
      peak appears at above the V-L edge (lambda = 2.42 nm) under grazing incidence.
      The V/Sc multilayer fabricated with a d-spacing of 1.59 nm and 30 bilayers has a
      smaller interface width (sigma = 0.27 and 0.32 nm) than the conventional used
      Cr/Sc (sigma = 0.28 and 0.47 nm). For V/Sc multilayer with 30 bilayers, the
      introduction of B4C barrier layers has little improvement on the interface
      structure. As the number of bilayers increasing to 400, the growth morphology and
      microstructure of the V/Sc layers evolves with slightly increased
      crystallization. Nevertheless, the surface roughness remains to be 0.25 nm. A
      maximum soft X-ray reflectance of 18.4% is measured at lambda = 3.129 nm at 9
      degrees  off-normal incidence using the 400-bilayers V/Sc multilayer. According
      to the fitted model, an s-polarization reflectance of 5.2% can also be expected
      at lambda = 2.425 nm under 40 degrees  incidence. Based on the promising
      experimental results, further improvement of the reflectance can be achieved by
      using a more stable deposition system, exploring different interface engineering
      methods and so on.

PMID- 29018233
TI  - Altered neurovascular coupling as measured by optical imaging: a biomarker for
      Alzheimer's disease.
AB  - Neurovascular coupling can be directly assessed by retinal vessel response to
      flickering light using optical imaging methods. The response is altered in a
      number of ocular and cardiovascular diseases. Whether it is altered in
      Alzheimer's disease (AD) is investigated. Retinal vessel reaction to
      monochromatic flicker stimulation was examined by Dynamic Vessel Analyzer
      independent of the commercial software in elderly subjects: 15 patients with mild
      to-moderate dementia due to AD (ADD); 24 patients with mild cognitive impairment
      due to AD (MCI); 15 cognitively healthy controls (HC). Retinal vessels in ADD
      showed a more emphasized and delayed reactive dilation as compared to HC. In MCI,
      these aspects still differed from those seen in ADD. Maximal arterial reaction
      was increased and dilation was delayed in ADD as compared to HC (p = 0.004 and p
      < 0.001) and to MCI (p = 0.058 and p = 0.004), respectively. Maximal venous
      reaction was increased in ADD as compared to HC (p = 0.001) and to MCI (p =
      0.007), respectively. This finding suggests that retinal neuronal activity is
      either increased or feed-back loop of neurovascular coupling is damaged with
      differentiating alterations across the spectrum of AD. Thus, retinal vessel
      reaction to flicker stimulation is considered a promising non-invasive, widely
      available and easy-to-administer future biomarker for the diagnosis and
      monitoring of AD.

PMID- 29018235
TI  - Phosphine inhibits transcription of the catalase gene through the DRE/DREF system
      in Drosophila melanogaster.
AB  - Phosphine (PH3) is a toxin commonly used for pest control. Its toxicity is
      attributed primarily to its ability to induce oxidative damage. Our previous work
      showed that phosphine could disrupt the cell antioxidant defence system by
      inhibiting expression of the catalase gene in Drosophila melanogaster (DmCAT).
      However, the exact mechanism of this inhibition remains unclear. Here, we
      implemented a luciferase reporter assay driven by the DmCAT promoter in D.
      melanogaster S2 cells and showed that this reporter could be inhibited by
      phosphine treatment. A minimal fragment of the promoter (-94 to 0 bp), which
      contained a DNA replication-related element (DRE) consensus motif (-78 to -85
      bp), was sufficient for phosphine-mediated reporter inhibition, suggesting the
      involvement of the transcription factor DREF. Furthermore, phosphine treatment
      led to a reduction in DREF expression and consequent repression of DmCAT
      transcription. Our results provide new insights on the molecular mechanism of
      phosphine-mediated catalase inhibition. Phosphine treatment leads to reduced
      levels of the transcription factor DREF, a positive regulator of the DmCAT gene,
      thereby resulting in the repression of DmCAT at transcriptional level.

PMID- 29018236
TI  - Automatic digital quantification of bone marrow myeloma volume in appendicular
      skeletons - clinical implications and prognostic significance.
AB  - Multiple myeloma (MM) is a clonal plasma cell disorder originating in bone
      marrow. Whole body low-dose multidetector CT (MDCT) can depict bone marrow
      infiltration by myeloma cells into the adipose-rich fatty marrow of the
      appendicular skeleton. However, automated and objective volume measurement of
      bone marrow infiltration has not been established, and its clinical relevance
      remains unclear. We therefore developed novel CT post-processing software (MABLE
      software) and measured the total sum of CT values (cumulative CT value, cCTv)
      representing bone marrow infiltration, by combining volume and voxel-based CT
      values. The cCTv was greater in patients with symptomatic MM than in those with
      smouldering MM or monoclonal gammopathy of unknown significance. Patients with
      revised International Staging System (R-ISS) III had a higher cCTv than those
      with R-ISS I or II. Age, albumin, and M-protein levels independently predicted
      cCTv. Mixed graphical model analysis revealed direct relationships between cCTv
      and age or R-ISS. Tree-structured survival analysis and multivariate Cox analysis
      revealed that a cCTv greater than or equal to 4.4 was independently prognostic
      for overall survival. Anti-myeloma therapy reduced cCTv after treatment. These
      findings suggest that the automatically calculated cCTv reflects disease
      aggressiveness and is useful for accurate prognostic prediction in MM patients.

PMID- 29018234
TI  - Homo-PROTACs: bivalent small-molecule dimerizers of the VHL E3 ubiquitin ligase
      to induce self-degradation.
AB  - E3 ubiquitin ligases are key enzymes within the ubiquitin proteasome system which
      catalyze the ubiquitination of proteins, targeting them for proteasomal
      degradation. E3 ligases are gaining importance as targets to small molecules,
      both for direct inhibition and to be hijacked to induce the degradation of non
      native neo-substrates using bivalent compounds known as PROTACs (for 'proteolysis
      targeting chimeras'). We describe Homo-PROTACs as an approach to dimerize an E3
      ligase to trigger its suicide-type chemical knockdown inside cells. We provide
      proof-of-concept of Homo-PROTACs using diverse molecules composed of two
      instances of a ligand for the von Hippel-Lindau (VHL) E3 ligase. The most active
      compound, CM11, dimerizes VHL with high avidity in vitro and induces potent,
      rapid and proteasome-dependent self-degradation of VHL in different cell lines,
      in a highly isoform-selective fashion and without triggering a hypoxic response.
      This approach offers a novel chemical probe for selective VHL knockdown, and
      demonstrates the potential for a new modality of chemical intervention on E3
      ligases.Targeting the ubiquitin proteasome system to modulate protein homeostasis
      using small molecules has promising therapeutic potential. Here the authors
      describe Homo-PROTACS: small molecules that can induce the homo-dimerization of
      E3 ubiquitin ligases and cause their proteasome-dependent degradation.

PMID- 29018237
TI  - High-throughput analysis unveils a highly shared satellite DNA library among
      three species of fish genus Astyanax.
AB  - The high-throughput analysis of satellite DNA (satDNA) content, by means of
      Illumina sequencing, unveiled 45 satDNA families in the genome of Astyanax
      paranae, with repeat unit length (RUL) ranging from 6 to 365 bp and marked
      predominance of short satellites (median length = 59 bp). The analysis of
      chromosomal location of 35 satDNAs in A. paranae, A. fasciatus and A. bockmanni
      revealed that most satellites are shared between the three species and show
      highly similar patterns of chromosome distribution. The high similarity in
      satellite DNA content between these species is most likely due to their recent
      common descent. Among the few differences found, the ApaSat44-21 satellite was
      present only on the B chromosome of A. paranae, but not on the A or B chromosomes
      of the two other species. Likewise, the ApaSat20-18 satellite was B-specific in
      A. paranae but was however present on A and B chromosomes of A. fasciatus and A.
      bockmanni. The isochromosome nature of B chromosomes in these species was
      evidenced by the symmetric location of many satDNAs on both B chromosome arms,
      and the lower symmetry observed in the A. fasciatus BfMa chromosome suggests that
      it is older than those analyzed in A. paranae and A. bockmanni.

PMID- 29018238
TI  - Smart patterned surfaces with programmable thermal emissivity and their design
      through combinatorial strategies.
AB  - The emissivity of common materials remains constant with temperature variations,
      and cannot drastically change. However, it is possible to design its entire
      behaviour as a function of temperature, and to significantly alter the thermal
      emissivity of a surface through the combination of different patterns and
      materials. We show that smart patterned surfaces consisting of smaller structures
      (motifs) may be designed to respond uniquely through combinatorial strategies by
      transforming themselves. The smart surfaces can passively manipulate thermal
      radiation-without the use of electronics-because their modus operandi has already
      been programmed into their intrinsic characteristics; the environment provides
      the energy required for their activation. Each motif emits thermal radiation in a
      certain manner, as it changes its geometry; however, the spatial distribution of
      these motifs causes them to interact with each other. Therefore, their
      combination and interaction determine the global behaviour of the surfaces, thus
      enabling their a priori design. The emissivity behaviour is not random; it is
      determined by two fundamental parameters, namely the combination of orientations
      in which the motifs open (n-fold rotational symmetry) and the combination of
      materials (colours) on the motifs; these generate functions which fully determine
      the dependency of the emissivity on the temperature.

PMID- 29018240
TI  - Buoyancy effects on the radiative magneto Micropolar nanofluid flow with double
      stratification, activation energy and binary chemical reaction.
AB  - A mathematical model has been developed to examine the magneto hydrodynamic
      micropolar nanofluid flow with buoyancy effects. Flow analysis is carried out in
      the presence of nonlinear thermal radiation and dual stratification. The impact
      of binary chemical reaction with Arrhenius activation energy is also considered.
      Apposite transformations are engaged to transform nonlinear partial differential
      equations to differential equations with high nonlinearity. Resulting nonlinear
      system of differential equations is solved by differential solver method in Maple
      software which uses Runge-Kutta fourth and fifth order technique (RK45). To
      authenticate the obtained results, a comparison with the preceding article is
      also made. The evaluations are executed graphically for numerous prominent
      parameters versus velocity, micro rotation component, temperature, and
      concentration distributions. Tabulated numerical calculations of Nusselt and
      Sherwood numbers with respective well-argued discussions are also presented. Our
      findings illustrate that the angular velocity component declines for opposing
      buoyancy forces and enhances for aiding buoyancy forces by changing the
      micropolar parameter. It is also found that concentration profile increases for
      higher values of chemical reaction parameter, whereas it diminishes for growing
      values of solutal stratification parameter.

PMID- 29018239
TI  - A blueprint for robust crosslinking of mobile species in biogels with weakly
      adhesive molecular anchors.
AB  - Biopolymeric matrices can impede transport of nanoparticulates and pathogens by
      entropic or direct adhesive interactions, or by harnessing "third-party"
      molecular anchors to crosslink nanoparticulates to matrix constituents. The
      trapping potency of anchors is dictated by association rates and affinities to
      both nanoparticulates and matrix; the popular dogma is that long-lived, high
      affinity bonds to both species facilitate optimal trapping. Here we present a
      contrasting paradigm combining experimental evidence (using IgG antibodies and
      Matrigel(r)), a theoretical framework (based on multiple timescale analysis), and
      computational modeling. Anchors that bind and unbind rapidly from matrix
      accumulate on nanoparticulates much more quickly than anchors that form high
      affinity, long-lived bonds with matrix, leading to markedly greater trapping
      potency of multiple invading species without saturating matrix trapping capacity.
      Our results provide a blueprint for engineering molecular anchors with finely
      tuned affinities to effectively enhance the barrier properties of biogels against
      diverse nanoparticulate species.Biological polymeric matrices often use molecular
      anchors, such as antibodies, to trap nanoparticulates. Here, the authors find
      that anchor-matrix bonds that are weak and short-lived confer superior trapping
      potency, contrary to the prevailing belief that effective molecular anchors
      should form strong bonds to both the matrix and the nanoparticulates.

PMID- 29018241
TI  - Eugenol inhibits oxidative phosphorylation and fatty acid oxidation via
      downregulation of c-Myc/PGC-1beta/ERRalpha signaling pathway in MCF10A-ras cells.
AB  - Alteration in cellular energy metabolism plays a critical role in the development
      and progression of cancer. Targeting metabolic pathways for cancer treatment has
      been investigated as potential preventive or therapeutic methods. Eugenol (Eu), a
      major volatile constituent of clove essential oil mainly obtained from Syzygium,
      has been reported as a potential chemopreventive drug. However, the mechanism by
      which Eu regulates cellular energy metabolism is still not well defined. This
      study was designed to determine the effect of Eu on cellular energy metabolism
      during early cancer progression employing untransformed and H-ras oncogene
      transfected MCF10A human breast epithelial cells. Eu showed dose-dependent
      selective cytotoxicity toward MCF10A-ras cells but exhibited no apparent
      cytotoxicity in MCF10A cells. Treatment with Eu also significantly reduced
      intracellular ATP levels in MCF10A-ras cells but not in MCF10A cells. This effect
      was mediated mainly through inhibiting oxidative phosphorylation (OXPHOS)
      complexs and the expression of fatty acid oxidation (FAO) proteins including
      PPARalpha, MCAD and CPT1C by downregulating c-Myc/PGC-1beta/ERRalpha pathway and
      decreasing oxidative stress in MCF10A-ras cells. These results indicate a novel
      mechanism involving the regulation of cellular energy metabolism by which Eu may
      prevent breast cancer progression.

PMID- 29018242
TI  - Nuclear factor (erythroid derived 2)-like 2 activation increases exercise
      endurance capacity via redox modulation in skeletal muscles.
AB  - Sulforaphane (SFN) plays an important role in preventing oxidative stress by
      activating the nuclear factor (erythroid derived 2)-like 2 (Nrf2) signalling
      pathway. SFN may improve exercise endurance capacity by counteracting oxidative
      stress-induced damage during exercise. We assessed running ability based on an
      exhaustive treadmill test (progressive-continuous all-out) and examined the
      expression of markers for oxidative stress and muscle damage. Twelve- to 13-week
      old Male wild-type mice (Nrf2 +/+) and Nrf2-null mice (Nrf2 -/-) on C57BL/6J
      background were intraperitoneally injected with SFN or vehicle prior to the test.
      The running distance of SFN-injected Nrf2 +/+ mice was significantly greater
      compared with that of uninjected mice. Enhanced running capacity was accompanied
      by upregulation of Nrf2 signalling and downstream genes. Marker of oxidative
      stress in SFN-injected Nrf2 +/+ mice were lower than those in uninjected mice
      following the test. SFN produced greater protection against muscle damage during
      exhaustive exercise conditions in Nrf2 +/+ mice than in Nrf2 -/- mice. SFN
      induced Nrf2 upregulation, and its antioxidative effects, might play critical
      roles in attenuating muscle fatigue via reduction of oxidative stress caused by
      exhaustive exercise. This in turn leads to enhanced exercise endurance capacity.
      These results provide new insights into SFN-induced upregulation of Nrf2 and its
      role in improving exercise performance.

PMID- 29018243
TI  - 6E11, a highly selective inhibitor of Receptor-Interacting Protein Kinase 1,
      protects cells against cold hypoxia-reoxygenation injury.
AB  - Necroptosis is a programmed cell death pathway that has been shown to be of
      central pathophysiological relevance in multiple disorders (hepatitis, brain and
      cardiac ischemia, pancreatitis, viral infection and inflammatory diseases).
      Necroptosis is driven by two serine threonine kinases, RIPK1 (Receptor
      Interacting Protein Kinase 1) and RIPK3, and a pseudo-kinase MLKL (Mixed Lineage
      Kinase domain-Like) associated in a multi-protein complex called necrosome. In
      order to find new inhibitors for use in human therapy, a chemical library
      containing highly diverse chemical structures was screened using a cell-based
      assay. The compound 6E11, a natural product derivative, was characterized as a
      positive hit. Interestingly, this flavanone compound: inhibits necroptosis
      induced by death receptors ligands TNF-alpha (Tumor Necrosis Factor) or TRAIL
      (TNF-Related Apoptosis-Inducing Ligand); is an extremely selective inhibitor,
      among kinases, of human RIPK1 enzymatic activity with a nM Kd; has a non-ATP
      competitive mode of action and a novel putative binding site; is weakly cytotoxic
      towards human primary blood leukocytes or retinal pigment epithelial cells at
      effective concentrations; protects human aortic endothelial cells (HAEC) from
      cold hypoxia/reoxygenation injury more effectively than necrostatin-1 (Nec-1) and
      Nec-1s. Altogether, these data demonstrate that 6E11 is a novel potent small
      molecular inhibitor of RIPK1-driven necroptosis.

PMID- 29018244
TI  - Bioengineering of functional human induced pluripotent stem cell-derived
      intestinal grafts.
AB  - Patients with short bowel syndrome lack sufficient functional intestine to
      sustain themselves with enteral intake alone. Transplantable vascularized
      bioengineered intestine could restore nutrient absorption. Here we report the
      engineering of humanized intestinal grafts by repopulating decellularized rat
      intestinal matrix with human induced pluripotent stem cell-derived intestinal
      epithelium and human endothelium. After 28 days of in vitro culture, hiPSC
      derived progenitor cells differentiate into a monolayer of polarized intestinal
      epithelium. Human endothelial cells seeded via native vasculature restore
      perfusability. Ex vivo isolated perfusion testing confirms transfer of glucose
      and medium-chain fatty acids from lumen to venous effluent. Four weeks after
      transplantation to RNU rats, grafts show survival and maturation of regenerated
      epithelium. Systemic venous sampling and positron emission tomography confirm
      uptake of glucose and fatty acids in vivo. Bioengineering intestine on
      vascularized native scaffolds could bridge the gap between cell/tissue-scale
      regeneration and whole organ-scale technology needed to treat intestinal failure
      patients.There is a need for humanised grafts to treat patients with intestinal
      failure. Here, the authors generate intestinal grafts by recellularizing native
      intestinal matrix with human induced pluripotent stem cell-derived epithelium and
      human endothelium, and show nutrient absorption after transplantation in rats.

PMID- 29018247
TI  - Gravitational-wave localization alone can probe origin of stellar-mass black hole
      mergers.
AB  - The recent discovery of gravitational waves from stellar-mass binary black hole
      mergers by the Laser Interferometer Gravitational-wave Observatory opened the
      door to alternative probes of stellar and galactic evolution, cosmology and
      fundamental physics. Probing the origin of binary black hole mergers will be
      difficult due to the expected lack of electromagnetic emission and limited
      localization accuracy. Associations with rare host galaxy types-such as active
      galactic nuclei-can nevertheless be identified statistically through spatial
      correlation. Here we establish the feasibility of statistically proving the
      connection between binary black hole mergers and active galactic nuclei as hosts,
      even if only a sub-population of mergers originate from active galactic nuclei.
      Our results are the demonstration that the limited localization of gravitational
      waves, previously written off as not useful to distinguish progenitor channels,
      can in fact contribute key information, broadening the range of astrophysical
      questions probed by binary black hole observations.Binary black hole mergers have
      recently been observed through the detection of gravitational wave signatures.
      The authors demonstrate that their association with active galactic nuclei can be
      made through a statistical spatial correlation.

PMID- 29018248
TI  - Sharing of science is most likely among male scientists.
AB  - Humans are considered to be highly prosocial, especially in comparison to other
      species. However, most tests of prosociality are conducted in highly artificial
      settings among anonymous participants. To gain a better understanding of how
      human hyper-cooperation may have evolved, we tested humans' willingness to share
      in one of the most competitive fields of our current society: academia.
      Researchers were generally prosocial with 80% sharing a PDF of one of their
      latest papers, and almost 60% willing to send us their data. Intriguingly,
      prosociality was most prominent from male to male, and less likely among all
      other sex-combinations. This pattern suggests the presence of male-exclusive
      networks in science, and may be based on an evolutionary history promoting strong
      male bonds.

PMID- 29018246
TI  - A minimal resting time of 25 min is needed before measuring stabilized blood
      pressure in subjects addressed for vascular investigations.
AB  - Blood pressure (BP) measurement is a central element in clinical practice.
      According to international recommendations 3 to 5 minutes of resting is needed
      before blood pressure measurement. Surprisingly, no study has modelled the time
      course of BP decrease and the minimum resting-time before BP measurement. A cross
      sectional bicentric observational study was performed including outpatients
      addressed for vascular examination. Using two automatic BP monitors we recorded
      the blood pressure every minute during 11 consecutive minutes. The data was
      analyzed by non-linear mixed effect regression. Systolic (SBP) and diastolic BPs
      were studied and we tested the effect of covariates on its evolution through log
      likelihood ratio tests. We included 199 patients (66+/-13years old). SBP was
      found to decrease exponentially. Simulations based on the final model show that
      only half the population reaches a stabilized SBP (defined as SBP + 5 mmHg) after
      5 min of resting-time while it takes 25 min to ensure 90% of the population has a
      stabilized SBP. In conclusion, our results and simulations suggest that 5 minutes
      are not enough to achieve a stabilized SBP in most patients and at least 25
      minutes are required. This questions whether the diagnosis of hypertension can be
      reliably made during routine visits in general practitioners' offices.

PMID- 29018245
TI  - Transient postnatal overfeeding causes liver stress-induced premature senescence
      in adult mice.
AB  - Unbalanced nutrition early in life is increasingly recognized as an important
      factor in the development of chronic, non-communicable diseases at adulthood,
      including metabolic diseases. We aimed to determine whether transient postnatal
      overfeeding (OF) leads to liver stress-induced premature senescence (SIPS) of
      hepatocytes in association with liver structure and hepatic function alterations.
      Litters sizes of male C57BL/6 mice were adjusted to 9 pups (normal feeding, NF)
      or reduced to 3 pups during the lactation period to induce transient postnatal
      OF. Compared to the NF group, seven-month-old adult mice transiently overfed
      during the postnatal period were overweight and developed glucose intolerance and
      insulin resistance. Their livers showed microsteatosis and fibrosis, while
      hepatic insulin signaling and glucose transporter protein expressions were
      altered. Increased hepatic oxidative stress (OS) was observed, with increased
      superoxide anion production, glucose-6-phosphate dehydrogenase protein
      expression, oxidative DNA damage and decreased levels of antioxidant defense
      markers, such as superoxide dismutase and catalase proteins. Hepatocyte
      senescence was characterized by increased p21WAF, p53, Acp53, p16INK4a and
      decreased pRb/Rb and Sirtuin-1 (SIRT-1) protein expression levels. Transient
      postnatal OF induces liver OS at adulthood, associated with hepatocyte SIPS and
      alterations in liver structure and hepatic functions, which could be mediated by
      a SIRT-1 deficiency.

PMID- 29018249
TI  - Systematic Moiety Variations of Ultrashort Peptides Produce Profound Effects on
      Self-Assembly, Nanostructure Formation, Hydrogelation, and Phase Transition.
AB  - Self-assembly of small biomolecules is a prevalent phenomenon that is
      increasingly being recognised to hold the key to building complex structures from
      simple monomeric units. Small peptides, in particular ultrashort peptides
      containing up to seven amino acids, for which our laboratory has found many
      biomedical applications, exhibit immense potential in this regard. For next
      generation applications, more intricate control is required over the self
      assembly processes. We seek to find out how subtle moiety variation of peptides
      can affect self-assembly and nanostructure formation. To this end, we have
      selected a library of 54 tripeptides, derived from systematic moiety variations
      from seven tripeptides. Our study reveals that subtle structural changes in the
      tripeptides can exert profound effects on self-assembly, nanostructure formation,
      hydrogelation, and even phase transition of peptide nanostructures. By comparing
      the X-ray crystal structures of two tripeptides, acetylated leucine-leucine
      glutamic acid (Ac-LLE) and acetylated tyrosine-leucine-aspartic acid (Ac-YLD), we
      obtained valuable insights into the structural factors that can influence the
      formation of supramolecular peptide structures. We believe that our results have
      major implications on the understanding of the factors that affect peptide self
      assembly. In addition, our findings can potentially assist current computational
      efforts to predict and design self-assembling peptide systems for diverse
      biomedical applications.

PMID- 29018250
TI  - Molecular analysis of pyrazinamide resistance in Mycobacterium tuberculosis in
      Vietnam highlights the high rate of pyrazinamide resistance-associated mutations
      in clinical isolates.
AB  - Pyrazinamide (PZA) is a key antibiotic in current anti-tuberculosis regimens.
      Although the WHO has stressed the urgent need to obtain data on PZA resistance,
      in high tuberculosis burden countries, little is known about the level of PZA
      resistance, the genetic basis of such resistance or its link with Mycobacterium
      tuberculosis families. In this context, this study assessed PZA resistance
      through the molecular analysis of 260 Vietnamese M. tuberculosis isolates. First
      line drug susceptibility testing, pncA gene sequencing, spoligotyping and
      mycobacterial interspersed repetitive units-variable number of tandem repeats
      (MIRU-VNTR) typing were performed. Overall, the pncA mutation frequency was 38.1%
      (99 out of 260 isolates) but was higher than 72% (89 out of 123 isolates) in
      multidrug and quadruple-drug resistant isolates. Many different pncA mutations
      (71 types) were detected, of which 55 have been previously described and 50 were
      linked to PZA resistance. Among the 16 novel mutations, 14 are likely to be
      linked to PZA resistance because of their mutation types or codon positions.
      Genotype analysis revealed that PZA resistance can emerge in any M. tuberculosis
      cluster or family, although the mutation frequency was the highest in Beijing
      family isolates (47.7%, 62 out of 130 isolates). These data highlight the high
      rate of PZA resistance-associated mutations in M. tuberculosis clinical isolates
      in Vietnam and bring into question the use of PZA for current and future
      treatment regimens of multidrug-resistant tuberculosis without PZA resistance
      testing.

PMID- 29018251
TI  - Epidemiology and antifungal susceptibility of candidemia isolates of non-albicans
      Candida species from cancer patients.
AB  - Candidemia is a growing concern worldwide, and its species distribution has
      shifted toward non-albicans Candida in recent decades, especially in patients
      with malignancy. This study aimed to update the epidemiology and antifungal
      susceptibility of non-albicans candidemia isolates from the cancer patients.
      Adult cancer patients with non-albicans candidemia were recruited, and clinical
      data were retrospectively collected from five medical centers in Taiwan from 1
      July 2011 to 30 June 2014. In vitro susceptibility was determined by the broth
      dilution method using a Sensititre YeastOne system and interpreted according to
      the guidelines of the Clinical and Laboratory Standards Institute. A total of 346
      episodes of non-albicans candidemia were identified in cancer patients. Candida
      tropicalis was the most common species (n=145, 41.9%) and had the highest
      resistance rate to fluconazole (n=17, 13.9%) among all the preserved isolates,
      including C. tropicalis, Candida glabrata and Candida parapsilosis. A higher
      Charlson comorbidity index, non-albicans candidemia due to C. tropicalis,
      neutropenia and septic shock were independent predictors of 28-day mortality. In
      conclusion, the species distribution and antifungal susceptibility of non
      albicans candidemia isolates in our study differed from those in Western
      countries, providing useful information about local epidemiology for the
      selection of empirical antifungal agents for cancer patients.

PMID- 29018252
TI  - Neutralization of Zika virus by germline-like human monoclonal antibodies
      targeting cryptic epitopes on envelope domain III.
AB  - The Zika virus (ZIKV), a flavivirus transmitted by Aedes mosquitoes, has emerged
      as a global public health concern. Pre-existing cross-reactive antibodies against
      other flaviviruses could modulate immune responses to ZIKV infection by antibody
      dependent enhancement, highlighting the importance of understanding the
      immunogenicity of the ZIKV envelope protein. In this study, we identified a panel
      of human monoclonal antibodies (mAbs) that target domain III (DIII) of the ZIKV
      envelope protein from a very large phage-display naive antibody library. These
      germline-like antibodies, sharing 98%-100% hoLogy with their corresponding
      germline IGHV genes, bound ZIKV DIII specifically with high affinities. One mAb,
      m301, broadly neutralized the currently circulating ZIKV strains and showed a
      synergistic effect with another mAb, m302, in neutralizing ZIKV in vitro and in a
      mouse model of ZIKV infection. Interestingly, epitope mapping and competitive
      binding studies suggest that m301 and m302 bind adjacent regions of the DIII C-C'
      loop, which represents a recently identified cryptic epitope that is
      intermittently exposed in an uncharacterized virus conformation. This study
      extended our understanding of antigenic epitopes of ZIKV antibodies and has
      direct implications for the design of ZIKV vaccines.

PMID- 29018254
TI  - Genetic variation of Sporothrix globosa isolates from diverse geographic and
      clinical origins in China.
AB  - Sporothrix globosa is the main causative agent of sporotrichosis, a common
      mycosis that usually affects the skin, in China. Despite increasing efforts in
      the molecular identification of this fungal pathogen, its modes of transmission
      and epidemiology remain poorly understood. The goals of this study were to assess
      the genetic diversity of S. globosa using amplified fragment length polymorphism
      (AFLP) analysis and to assess the correlation of AFLP profiles with the
      geographic origins, growth rates, clinical forms, and antifungal susceptibilities
      of S. globosa isolates. AFLP analysis of 225 clinical S. globosa isolates from
      eight provinces or municipalities in China identified eight distinct clustering
      groups (I-VIII), with groups I, II and IV being the most common. The AFLP
      genotypes showed distinct distribution patterns among different regions within
      Jilin Province and between northern and southern China, but there was no obvious
      association between the AFLP genotypes and the growth rates, clinical forms or
      antifungal susceptibilities of the S. globosa isolates. These results expand our
      understanding of the genetic variation of S. globosa and suggest that AFLP
      analysis is a potentially useful tool for studying the epidemiology of this
      fungal pathogen.

PMID- 29018255
TI  - Shuttling single metal atom into and out of a metal nanoparticle.
AB  - It has long been a challenge to dope metal nanoparticles with a specific number
      of heterometal atoms at specific positions. This becomes even more challenging if
      the heterometal belongs to the same group as the host metal because of the high
      tendency of forming a distribution of alloy nanoparticles with different numbers
      of dopants due to the similarities of metals in outmost electron configuration.
      Herein we report a new strategy for shuttling a single Ag or Cu atom into a
      centrally hollow, rod-shaped Au24 nanoparticle, forming AgAu24 and CuAu24
      nanoparticles in a highly controllable manner. Through a combined approach of
      experiment and theory, we explain the shuttling pathways of single dopants into
      and out of the nanoparticles. This study shows that the single dopant is shuttled
      into the hollow Au24 nanoparticle either through the apex or side entry, while
      shuttling a metal atom out of the Au25 to form the Au24 nanoparticle occurs
      mainly through the side entry.Doping a metal nanocluster with heteroatoms
      dramatically changes its properties, but it remains difficult to dope with single
      atom control. Here, the authors devise a strategy to dope single atoms of Ag or
      Cu into hollow Au nanoclusters, creating precise alloy nanoparticles atom-by
      atom.

PMID- 29018256
TI  - Sodium chloride effect on the aggregation behaviour of rhamnolipids and their
      antifungal activity.
AB  - In this work, the antifungal activity of rhamnolipids produced by Pseudomonas
      aeruginosa #112 was evaluated against Aspergillus niger MUM 92.13 and Aspergillus
      carbonarius MUM 05.18. It was demonstrated that the di-rhamnolipid congeners were
      responsible for the antifungal activity exhibited by the crude rhamnolipid
      mixture, whereas mono-rhamnolipids showed a weak inhibitory activity.
      Furthermore, in the presence of NaCl (from 375 mM to 875 mM), the antifungal
      activity of the crude rhamnolipid mixture and the purified di-rhamnolipids was
      considerably increased. Dynamic Light Scattering studies showed that the size of
      the structures formed by the rhamnolipids increased as the NaCl concentration
      increased, being this effect more pronounced in the case of di-rhamnolipids.
      These results were confirmed by Confocal Scanning Laser Microscopy, which
      revealed the formation of giant vesicle-like structures (in the um range) by self
      assembling of the crude rhamnolipid mixture in the presence of 875 mM NaCl. In
      the case of the purified mono- and di-rhamnolipids, spherical structures (also in
      the um range) were observed at the same conditions. The results herein obtained
      demonstrated a direct relationship between the rhamnolipids antifungal activity
      and their aggregation behaviour, opening the possibility to improve their
      biological activities for application in different fields.

PMID- 29018253
TI  - Usutu virus, Austria and Hungary, 2010-2016.
AB  - Usutu virus (USUV, Flaviviridae) was first reported in Europe in Austria in 2001,
      where it caused wild bird (mainly blackbird) mortality until 2005. Since 2006 no
      further USUV cases were diagnosed in the country. However, the virus emerged in
      other European countries (Hungary, Italy, Switzerland, Spain, Germany and the
      Czech Republic) between 2005 and 2011. In 2016, widespread USUV-associated wild
      bird mortality was observed in Germany, France, Belgium and the Netherlands. In
      this study, we report the results of passive monitoring for USUV in Austria and
      Hungary between 2010 and 2016. In Hungary, USUV caused sporadic cases of wild
      bird mortality between 2010 and 2015 (altogether 18 diagnosed cases), whereas in
      summer and autumn 2016 the number of cases considerably increased to 12 (ten
      blackbirds, one Eurasian jay and one starling). In Austria, USUV was identified
      in two blackbirds in 2016. Phylogenetic analyses of coding-complete genomes and
      partial regions of the NS5 protein gene revealed that USUVs from Hungary between
      2010 and 2015 are closely related to the virus that emerged in Austria in 2001
      and in Hungary in 2005, while one Hungarian sequence from 2015 and all sequences
      from Hungary and Austria from 2016 clustered together with USUV sequences
      reported from Italy between 2009 and 2010. The results of the study indicate
      continuous USUV circulation in the region and exchange of USUV strains between
      Italy, Austria and Hungary.Emerging Microbes &Infections (2017) 6, e85;
      doi:10.1038/emi.2017.72; published online 11 October 2017.

PMID- 29018257
TI  - Direct Writing with Tilted-Front Femtosecond Pulses.
AB  - Shaping light fields in both space and time provides new degrees of freedom to
      manipulate light-matter interaction on the ultrafast timescale. Through this
      exploitation of the light field, a greater appreciation of spatio-temporal
      couplings in focusing has been gained, shedding light on previously unexplored
      parameters of the femtosecond light pulse, including pulse front tilt and
      wavefront rotation. Here, we directly investigate the effect of major spatio
      temporal couplings on light-matter interaction and reveal unambiguously that in
      transparent media, pulse front tilt gives rise to the directional asymmetry of
      the ultrafast laser writing. We demonstrate that the laser pulse with a tilted
      intensity front deposits energy more efficiently when writing along the tilt than
      when writing against, producing either an isotropic damage-like or a birefringent
      nanograting structure. The directional asymmetry in the ultrafast laser writing
      is qualitatively described in terms of the interaction of a void trapped within
      the focal volume by the gradient force from the tilted intensity front and the
      thermocapillary force caused by the gradient of temperature. The observed
      instantaneous transition from the damage-like to nanograting modification after a
      finite writing length in a transparent dielectric is phenomenologically described
      in terms of the first-order phase transition.

PMID- 29018258
TI  - Future soil moisture and temperature extremes imply expanding suitability for
      rainfed agriculture in temperate drylands.
AB  - The distribution of rainfed agriculture, which accounts for approximately 3/4 of
      global croplands, is expected to respond to climate change and human population
      growth and these responses may be especially pronounced in water limited areas.
      Because the environmental conditions that support rainfed agriculture are
      determined by climate, weather, and soil conditions that affect overall and
      transient water availability, predicting this response has proven difficult,
      especially in temperate regions that support much of the world's agriculture.
      Here, we show that suitability to support rainfed agriculture in temperate
      dryland climates can be effectively represented by just two daily environmental
      variables: moist soils with warm conditions increase suitability while extreme
      high temperatures decrease suitability. 21st century projections based on daily
      ecohydrological modeling of downscaled climate forecasts indicate overall
      increases in the area suitable for rainfed agriculture in temperate dryland
      regions, especially at high latitudes. The regional exception to this trend was
      Europe, where suitability in temperate dryland portions will decline
      substantially. These results clarify how rising temperatures interact with other
      key drivers of moisture availability to determine the sustainability of rainfed
      agriculture and help policymakers, resource managers, and the agriculture
      industry anticipate shifts in areas suitable for rainfed cultivation.

PMID- 29018259
TI  - Clinicopathological and molecular characteristics of synchronous gastric
      adenocarcinoma and gastrointestinal stromal tumors.
AB  - Synchronous gastric tumors that consist of both gastrointestinal stromal tumor
      (GIST) and adenocarcinoma are rare. We studied the clinicopathological and
      molecular characteristics of six cases containing both gastric adenocarcinoma and
      GIST. By means of immunohistochemical analysis, all GIST cells expressed CD117,
      CD34 and Dog1 in all six synchronous gastric adenocarcinomas with GIST, and in
      GIST alone. Sequencing analysis demonstrated that exon 11 c-kit mutations were
      present in two of six synchronous tumors and four of five GISTs. One of the two
      exon 11 c-kit mutations in synchronous adenocarcinomas with GISTs was an uncommon
      mutation of CTT > CCA at amino acid 576, and the other was a GTT deletion at
      amino acid 560. The mutation was a homozygous A > G mutation in exon 12 (amino
      acid 567) of PDGFR-alpha. We concluded that the exon 11 mutations were the most
      important in both cases of synchronous gastric adenocarcinoma with GIST and GIST
      alone. The mutation rate was higher in GIST alone than in synchronous
      adenocarcinoma with GIST.

PMID- 29018260
TI  - Control of chrysanthemum flowering through integration with an aging pathway.
AB  - Age, as a threshold of floral competence acquisition, prevents precocious
      flowering when there is insufficient biomass, and ensures flowering independent
      of environmental conditions; however, the underlying regulatory mechanisms are
      largely unknown. In this study, silencing the expression of a nuclear factor
      gene, CmNF-YB8, from the short day plant chrysanthemum (Chrysanthemum
      morifolium), results in precocious transition from juvenile to adult, as well as
      early flowering, regardless of day length conditions. The expression of SQUAMOSA
      PROMOTER BINDING-LIKE (SPL) family members, SPL3, SPL5, and SPL9, is upregulated
      in CmNF-YB8-RNAi plants, while expression of the microRNA, cmo-MIR156, is
      downregulated. In addition, CmNF-YB8 is shown to bind to the promoter of the cmo
      MIR156 gene. Ectopic expression of cmo-miR156, using a virus-based microRNA
      expression system, restores the early flowering phenotype caused by CmNF-YB8
      silencing. These results show that CmNF-YB8 influences flowering time through
      directly regulating the expression of cmo-MIR156 in the aging pathway.The
      mechanisms by which plant age regulates flowering remain incompletely understood.
      Here the authors show that age dependent regulation of SPL transcription factors
      by miR156 influence flowering via control of NF-YB8 expression in Chrysanthemum.

PMID- 29018262
TI  - A Cu-atom-chain current channel with a width of approximately 0.246 nm on (5, 0)
      single-wall carbon nanotube.
AB  - Continuous miniaturization with improved performance has enabled the development
      of electronic devices. However, further shrinking of electronic circuits will
      push feature sizes (linewidths) firmly into the nanoscale. This can cause
      electronic devices built using current materials (silicon-based) and fabrication
      processes to not work as expected. Therefore, new materials or preparation
      technologies are needed for the further miniaturization of electron devices.
      Here, through theoretical simulation, we show that regular doping of a Cu-atom
      chain on a single-wall carbon nanotube (SWCNT) can be used to realize an atomic
      scale current channel (Cu-atom-chain current channel) with a linewidth of
      approximately 0.246 nm. Moreover, the atomic-scale Cu-atom-chain current channel
      shows enhanced conductivity (lower power consumption) compared to a pristine
      SWCNT. Such a Cu-atom-chain current channel with an atomic-scale linewidth and
      its method of fabrication (regular doping) may be suitable for the preparation of
      nanoelectronic devices.

PMID- 29018263
TI  - Phyllomeroterpenoids A-C, Multi-biosynthetic Pathway Derived Meroterpenoids from
      the TCM Endophytic Fungus Phyllosticta sp. and their Antimicrobial Activities.
AB  - Phyllomeroterpenoids A-C (1-3), multi-biosynthetic pathway derived meroterpenoids
      from amino acid/pentose phosphate/terpenoid pathways, were isolated from the TCM
      endophytic fungus Phyllosticta sp. J13-2-12Y, together with six biosynthetically
      related compounds (4-9). All structures were determined by extensive
      spectroscopic analysis, chemical derivatization, and ECD experiments. A plausible
      biosynthetic pathway of 1-3 was proposed. In addition, the antimicrobial
      activities of all isolated compounds were evaluated against Staphylococcus aureus
      209P (bacterium) and Candida albicans FIM709 (fungus).

PMID- 29018261
TI  - Alveolar macrophages are critical for broadly-reactive antibody-mediated
      protection against influenza A virus in mice.
AB  - The aim of candidate universal influenza vaccines is to provide broad protection
      against influenza A and B viruses. Studies have demonstrated that broadly
      reactive antibodies require Fc-Fc gamma receptor interactions for optimal
      protection; however, the innate effector cells responsible for mediating this
      protection remain largely unknown. Here, we examine the roles of alveolar
      macrophages, natural killer cells, and neutrophils in antibody-mediated
      protection. We demonstrate that alveolar macrophages play a dominant role in
      conferring protection provided by both broadly neutralizing and non-neutralizing
      antibodies in mice. Our data also reveal the potential mechanisms by which
      alveolar macrophages mediate protection in vivo, namely antibody-induced
      inflammation and antibody-dependent cellular phagocytosis. This study highlights
      the importance of innate effector cells in establishing a broad-spectrum
      antiviral state, as well as providing a better understanding of how multiple arms
      of the immune system cooperate to achieve an optimal antiviral response following
      influenza virus infection or immunization.Broadly reactive antibodies that
      recognize influenza A virus HA can be protective, but the mechanism is not
      completely understood. Here, He et al. show that the inflammatory response and
      phagocytosis mediated by the interaction between protective antibodies and
      macrophages are essential for protection.

PMID- 29018264
TI  - Anthraquinones from the saline-alkali plant endophytic fungus Eurotium rubrum.

PMID- 29018265
TI  - Ascosteroside D, a new mitochondrial respiration inhibitor discovered by
      pesticidal screening using insect ADP/ATP carrier protein-expressing
      Saccharomyces cerevisiae.
AB  - A new lanostane-type triterpenoid, ascosteroside D, was isolated from a fungus,
      Aspergillus sp. FKI-6682. It inhibited insect ADP/ATP carrier protein (AAC)
      expressing Saccharomyces cerevisiae in glycerol-containing medium, but did not
      inhibit Deltaaac S. cerevisiae in glucose-containing medium. It is hypothesized
      that ascosteroside D inhibits ATP production in mitochondria.The Journal of
      Antibiotics advance online publication, 11 October 2017; doi:10.1038/ja.2017.118.

PMID- 29018266
TI  - Large-scale preparation of key building blocks for the manufacture of fully
      synthetic macrolide antibiotics.
AB  - Key building blocks for the production of fully synthetic macrolides have been
      scaled-up in first time pilot plant and kilo-lab campaigns. These building blocks
      have supported the discovery of new macrolide antibiotics as well as ongoing
      preclinical studies.

PMID- 29018268
TI  - Biological activity of intervenolin analogs with a phenyl substituent.
AB  - Intervenolin analogs with a phenyl substituent at the 2- or 3-position were
      synthesized. The compounds (3-11) showed weak or no inhibitory activity toward
      the growth of MKN-74 gastric adenocarcinoma cells, even in the presence or
      absence of the corresponding Hs738 stromal cells, whereas 2-substituted analogs
      exhibited selective anti-Helicobacter pylori activity. Introduction of a pendant
      side chain on the nitrogen alleviated their acute toxicity in mice. The 2-phenyl
      substituted analogs are reasonable structural templates for structure-activity
      relationship studies toward the development of anti-H. pylori agents that do not
      affect human cells.The Journal of Antibiotics advance online publication, 11
      October 2017; doi:10.1038/ja.2017.123.

PMID- 29018270
TI  - NAFLD: Early promise for ASK1 inhibition in NASH.

PMID- 29018267
TI  - Current landscape and future prospects of antiviral drugs derived from microbial
      products.
AB  - Viral infections are a major global health threat. Over the last 50 years,
      significant efforts have been devoted to the development of antiviral drugs and
      great success has been achieved for some viruses. However, other virus
      infections, such as epidemic influenza, still spread globally and new threats
      continue to arise from emerging and re-emerging viruses and drug-resistant
      viruses. In this review, the contributions of microbial products isolated in
      Institute of Microbial Chemistry for antiviral research are summarized. In
      addition, the current state of development of antiviral drugs that target
      influenza virus and hepatitis B virus, and the future prospects for antivirals
      from natural products are described and discussed.The Journal of Antibiotics
      advance online publication, 11 October 2017; doi:10.1038/ja.2017.115.

PMID- 29018269
TI  - ADAR1 polymorphisms are related to severity of liver fibrosis in HIV/HCV
      coinfected patients.
AB  - The adenosine deaminase acting on RNA (ADAR1) gene is an interferon-stimulated
      gene involved in liver injury protection. Our aim was to analyze the association
      of polymorphisms within this gene with the severity of liver disease in European
      HIV/HCV-coinfected patients. We performed a cross-sectional study in 220 patients
      that underwent a liver biopsy. Five SNPs in the ADAR1 gene (rs1127326, rs1127317,
      rs1127314, rs1127313, rs2229857) were genotyped by GoldenGate assay. The outcome
      variables were fibrosis stage and necroinflammatory activity grade by METAVIR
      score, aspartate aminotransferase to platelet ratio index (APRI), FIB-4 index,
      and fibrosis progression rate (FPR). In multivariate analysis, fibrosis
      progression rate (FPR) (aAMRs = 0.97) decreased in a dose-dependent manner with
      the presence of rs2229857_T, rs1127313_G, rs1127314_G and rs1127317_G; while
      rs1127326_T allele had only significant associations with FIB-4 (aAMRs <= 0.63)
      and FPR (aAMRs <= 0.97). Moreover, carriers of rs2229857_T, rs1127314_G,
      rs1127317_G, and rs1127326_T alleles were protected against advanced fibrosis (F
      >= 3) (adjusted ORs (aORs) <= 0.44), APRI >= 1.5 (aORs <= 0.33), and FPR >= 0.075
      (aORs <= 0.45). rs1127313_G carriers showed lower odds of having F >= 3 (aORs =
      0.39), FIB4 >= 3.25 (aOR = 0.22) and FPR >= 0.075 (aORs = 0.44). In conclusion,
      ADAR1 polymorphisms protected against severe liver disease in HIV/HCV-coinfected
      patients. These results could be used to improve therapeutic decision-making in
      clinical practice.

PMID- 29018273
TI  - Pancreatic cancer: Intra-tumour bacteria promote gemcitabine resistance in
      pancreatic adenocarcinoma.

PMID- 29018271
TI  - Environmental triggers in IBD: a review of progress and evidence.
AB  - A number of environmental factors have been associated with the development of
      IBD. Alteration of the gut microbiota, or dysbiosis, is closely linked to
      initiation or progression of IBD, but whether dysbiosis is a primary or secondary
      event is unclear. Nevertheless, early-life events such as birth, breastfeeding
      and exposure to antibiotics, as well as later childhood events, are considered
      potential risk factors for IBD. Air pollution, a consequence of the progressive
      contamination of the environment by countless compounds, is another factor
      associated with IBD, as particulate matter or other components can alter the
      host's mucosal defences and trigger immune responses. Hypoxia associated with
      high altitude is also a factor under investigation as a potential new trigger of
      IBD flares. A key issue is how to translate environmental factors into mechanisms
      of IBD, and systems biology is increasingly recognized as a strategic tool to
      unravel the molecular alterations leading to IBD. Environmental factors add a
      substantial level of complexity to the understanding of IBD pathogenesis but also
      promote the fundamental notion that complex diseases such as IBD require complex
      therapies that go well beyond the current single-agent treatment approach. This
      Review describes the current conceptualization, evidence, progress and direction
      surrounding the association of environmental factors with IBD.

PMID- 29018275
TI  - Gut microbiota: Human faecal sample processing in metagenomic studies: striving
      for standards.

PMID- 29018274
TI  - Current and emerging therapeutic targets for IBD.
AB  - This corrects the article DOI: 10.1038/nrgastro.2016.208.

PMID- 29018277
TI  - Immunology: Regulatory ILCs help control intestinal inflammation.

PMID- 29018276
TI  - IBD: Step-up vs top-down therapy for Crohn's disease: medicine vs surgery.

PMID- 29018281
TI  - Cell death: BCL-2 proteins feed their own expression.

PMID- 29018278
TI  - Coeliac disease: to biopsy or not?
AB  - Coeliac disease is increasingly recognized as a global problem in both children
      and adults. Traditionally, the findings of characteristic changes of villous
      atrophy and increased intraepithelial lymphocytosis identified in duodenal biopsy
      samples taken during upper gastrointestinal endoscopy have been required for
      diagnosis. Although biopsies remain advised as necessary for the diagnosis of
      coeliac disease in adults, European guidelines for children provide a biopsy
      sparing diagnostic pathway. This approach has been enabled by the high
      specificity and sensitivity of serological testing. However, these guidelines are
      not universally accepted. In this Perspective, we discuss the pros and cons of a
      biopsy-avoiding pathway for the diagnosis of coeliac disease, especially in this
      current era of the call for more biopsies, even from the duodenal bulb, in the
      diagnosis of coeliac disease. In addition, a contrast between paediatric and
      adult guidelines is presented.

PMID- 29018279
TI  - Sodium fluorocitrate having protective effect on palmitate-induced beta cell
      death improves hyperglycemia in diabetic db/db mice.
AB  - Beta cell loss and insulin resistance play roles in the pathogenesis of type 2
      diabetes. Elevated levels of free fatty acids in plasma might contribute to the
      loss of beta cells. The objective of this study was to find a chemical that could
      protect against palmitate-induced beta cell death and investigate whether such
      chemical could improve hyperglycemia in mouse model of type 2 diabetes. Sodium
      fluorocitrate (SFC), an aconitase inhibitor, was found to be strongly and
      specifically protective against palmitate-induced INS-1 beta cell death. However,
      the protective effect of SFC on palmitate-induced cell death was not likely to be
      due to its inhibitory activity for aconitase since inhibition or knockdown of
      aconitase failed to protect against palmitate-induced cell death. Since SFC
      inhibited the uptake of palmitate into INS-1 cells, reduced metabolism of fatty
      acids was thought to be involved in SFC's protective effect. Ten weeks of
      treatment with SFC in db/db diabetic mice reduced glucose level but remarkably
      increased insulin level in the plasma. SFC improved impairment of glucose
      stimulated insulin release and also reduced the loss of beta cells in db/db mice.
      Conclusively, SFC possessed protective effect against palmitate-induced
      lipotoxicity and improved hyperglycemia in mouse model of type 2 diabetes.

PMID- 29018272
TI  - Bile acid-microbiota crosstalk in gastrointestinal inflammation and
      carcinogenesis.
AB  - Emerging evidence points to a strong association between the gut microbiota and
      the risk, development and progression of gastrointestinal cancers such as
      colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Bile acids, produced
      in the liver, are metabolized by enzymes derived from intestinal bacteria and are
      critically important for maintaining a healthy gut microbiota, balanced lipid and
      carbohydrate metabolism, insulin sensitivity and innate immunity. Given the
      complexity of bile acid signalling and the direct biochemical interactions
      between the gut microbiota and the host, a systems biology perspective is
      required to understand the liver-bile acid-microbiota axis and its role in
      gastrointestinal carcinogenesis to reverse the microbiota-mediated alterations in
      bile acid metabolism that occur in disease states. An examination of recent
      research progress in this area is urgently needed. In this Review, we discuss the
      mechanistic links between bile acids and gastrointestinal carcinogenesis in CRC
      and HCC, which involve two major bile acid-sensing receptors, farnesoid X
      receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5). We also
      highlight the strategies and cutting-edge technologies to target gut-microbiota
      dependent alterations in bile acid metabolism in the context of cancer therapy.

PMID- 29018280
TI  - DUSP5 functions as a feedback regulator of TNFalpha-induced ERK1/2
      dephosphorylation and inflammatory gene expression in adipocytes.
AB  - Adipose tissue inflammation is a central pathological element that regulates
      obesity-mediated insulin resistance and type II diabetes. Evidence demonstrates
      that extracellular signal-regulated kinase (ERK 1/2) activation (i.e.
      phosphorylation) links tumor necrosis factor alpha (TNFalpha) to pro-inflammatory
      gene expression in the nucleus. Dual specificity phosphatases (DUSPs) inactivate
      ERK 1/2 through dephosphorylation and can thus inhibit inflammatory gene
      expression. We report that DUSP5, an ERK1/2 phosphatase, was induced in
      epididymal white adipose tissue (WAT) in response to diet-induced obesity.
      Moreover, DUSP5 mRNA expression increased during obesity development concomitant
      to increases in TNFalpha expression. Consistent with in vivo findings, DUSP5 mRNA
      expression increased in adipocytes in response to TNFalpha, parallel with ERK1/2
      dephosphorylation. Genetic loss of DUSP5 exacerbated TNFalpha-mediated ERK 1/2
      signaling in 3T3-L1 adipocytes and in adipose tissue of mice. Furthermore,
      inhibition of ERK 1/2 and c-Jun N terminal kinase (JNK) signaling attenuated
      TNFalpha-induced DUSP5 expression. These data suggest that DUSP5 functions in the
      feedback inhibition of ERK1/2 signaling in response to TNFalpha, which resulted
      in increased inflammatory gene expression. Thus, DUSP5 potentially acts as an
      endogenous regulator of adipose tissue inflammation; although its role in obesity
      mediated inflammation and insulin signaling remains unclear.

PMID- 29018284
TI  - The discovery of catalytic RNA.

PMID- 29018282
TI  - Emerging roles of linker histones in regulating chromatin structure and function.
AB  - Together with core histones, which make up the nucleosome, the linker histone
      (H1) is one of the five main histone protein families present in chromatin in
      eukaryotic cells. H1 binds to the nucleosome to form the next structural unit of
      metazoan chromatin, the chromatosome, which may help chromatin to fold into
      higher-order structures. Despite their important roles in regulating the
      structure and function of chromatin, linker histones have not been studied as
      extensively as core histones. Nevertheless, substantial progress has been made
      recently. The first near-atomic resolution crystal structure of a chromatosome
      core particle and an 11 A resolution cryo-electron microscopy-derived structure
      of the 30 nm nucleosome array have been determined, revealing unprecedented
      details about how linker histones interact with the nucleosome and organize
      higher-order chromatin structures. Moreover, several new functions of linker
      histones have been discovered, including their roles in epigenetic regulation and
      the regulation of DNA replication, DNA repair and genome stability. Studies of
      the molecular mechanisms of H1 action in these processes suggest a new paradigm
      for linker histone function beyond its architectural roles in chromatin.

PMID- 29018285
TI  - The ultrastructure of spinal cord perivascular spaces: Implications for the
      circulation of cerebrospinal fluid.
AB  - Perivascular spaces play a pivotal role in the exchange between cerebrospinal and
      interstitial fluids, and in the clearance of waste in the CNS, yet their precise
      anatomical components are not well described. The aim of this study was to
      characterise the ultrastructure of perivascular spaces and their role in the
      transport of fluid, in the spinal cord of healthy rats, using transmission
      electron microscopy. The distribution of cerebrospinal fluid tracers injected
      into the subarachnoid space was studied using light, confocal and electron
      microscopy. Perivascular spaces were found around arterioles and venules, but not
      capillaries, throughout the spinal cord white and grey matter. They contained
      fibroblasts and collagen fibres, and were continuous with the extracellular
      spaces of the surrounding tissue. At 5 min post injection, tracers were seen in
      the subarachnoid space, the peripheral white matter, the perivascular spaces,
      basement membranes, extracellular spaces of the surrounding tissue, and
      surprisingly, in the lumen of blood vessels, suggesting trans-vascular clearance.
      These findings point out an unrecognised outflow pathway for CNS fluids, with
      potential implications for volume regulation in health and disease states, but
      also clinically for the detection of CNS-derived biomarkers in plasma, the immune
      response and drug pharmacokinetics.

PMID- 29018287
TI  - Large piezoelectric strain with ultra-low strain hysteresis in highly c-axis
      oriented Pb(Zr0.52Ti0.48)O3 films with columnar growth on amorphous glass
      substrates.
AB  - Thin films of PbZr0.52Ti0.48O3 (PZT) with largely detached columnar grains,
      deposited by pulsed laser deposition (PLD) on amorphous glass substrates covered
      with Ca2Nb3O10 nanosheets as growth template and using LaNiO3 electrode layers,
      are shown to exhibit very high unipolar piezoelectric strain and ultra-low strain
      hysteresis. The observed increase of the piezoelectric coefficient with
      increasing film thickness is attributed to the reduction of clamping, because of
      the increasingly less dense columnar microstructure (more separation between the
      grains) with across the film thickness. A very large piezoelectric coefficient
      (490 pm/V) and a high piezoelectric strain (~0.9%) are obtained in 4-um-thick
      film under an applied electric field of 200 kV/cm, which is several times larger
      than in usual PZT ceramics. Further very low strain hysteresis (H~2-4%) is
      observed in 4 to 5 um thick films. These belong to the best values demonstrated
      so far in piezoelectric films. Fatigue testing shows that the piezoelectric
      properties are stable up to 1010 cycles. The growth of high quality PZT films
      with very large strain and piezoelectric coefficients, very low hysteresis and
      with long-term stability on a technologically important substrate as glass is of
      great significance for the development of practical piezo driven
      microelectromechanical actuator systems.

PMID- 29018283
TI  - Codon optimality, bias and usage in translation and mRNA decay.
AB  - The advent of ribosome profiling and other tools to probe mRNA translation has
      revealed that codon bias - the uneven use of synonymous codons in the
      transcriptome - serves as a secondary genetic code: a code that guides the
      efficiency of protein production, the fidelity of translation and the metabolism
      of mRNAs. Recent advancements in our understanding of mRNA decay have revealed a
      tight coupling between ribosome dynamics and the stability of mRNA transcripts;
      this coupling integrates codon bias into the concept of codon optimality, or the
      effects that specific codons and tRNA concentrations have on the efficiency and
      fidelity of the translation machinery. In this Review, we first discuss the
      evidence for codon-dependent effects on translation, beginning with the basic
      mechanisms through which translation perturbation can affect translation
      efficiency, protein folding and transcript stability. We then discuss how codon
      effects are leveraged by the cell to tailor the proteome to maintain homeostasis,
      execute specific gene expression programmes of growth or differentiation and
      optimize the efficiency of protein production.

PMID- 29018286
TI  - Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss.
AB  - The inflammatory response to spinal cord injury (SCI) involves localization and
      activation of innate and adaptive immune cells and proteins, including the
      complement cascade. Complement C3 is important for the classical, alternative,
      and lectin pathways of complement activation, and its cleavage products C3a and
      C3b mediate several functions in the context of inflammation, but little is known
      about the potential functions of C3 on regeneration and survival of injured
      neurons after SCI. We report that 6 weeks after dorsal hemisection with
      peripheral conditioning lesion, C3-/- mice demonstrated a 2-fold increase in
      sensory axon regeneration in the spinal cord in comparison to wildtype C3+/+
      mice. In vitro, addition of C3 tripled both myelin-mediated neurite outgrowth
      inhibition and neuron loss versus myelin alone, and ELISA experiments revealed
      that myelin serine proteases cleave C3 to generate active fragments. Addition of
      purified C3 cleavage products to cultured neurons suggested that C3b is
      responsible for the growth inhibitory and neurotoxic or anti-adhesion activities
      of C3. These data indicate that C3 reduces neurite outgrowth and neuronal
      viability in vitro and restricts axon regeneration in vivo, and demonstrate a
      novel, non-traditional role for this inflammatory protein in the central nervous
      system.

PMID- 29018289
TI  - Genome-wide open chromatin regions and their effects on the regulation of silk
      protein genes in Bombyx mori.
AB  - Nucleosome-depleted open chromatin regions (OCRs) often harbor transcription
      factor (TF) binding sites that are associated with active DNA regulatory
      elements. To investigate the regulation of silk-protein genes, DNA molecules
      isolated from the silk glands of third-day fifth-instar silkworm larvae and
      embryo-derived (BmE) cells were subjected to formal dehyde-assisted isolation of
      regulatory elements (FAIRE) and high-throughput sequencing. In total, 68,000 OCRs
      were identified, and a number of TF-binding motifs were predicted. In particular,
      OCRs located near silk-protein genes contained potential binding sites for
      functional TFs. Moreover, many TFs were found to bind to clusters of OCRs
      upstream of silk-protein genes, and to regulate the expression of these genes.
      The expression of silk protein genes may be related not only to regulating TFs
      (such as fkh, Bmdimm, and Bmsage), but also to developmental and hormone-induced
      TFs (such as zen, eve, Br, and eip74ef). Elucidation of genome-wide OCRs and
      their regulatory motifs in silk protein genes will provide valuable data and
      clues for characterizing the mechanisms of transcriptional control of silk
      protein genes.

PMID- 29018288
TI  - Macropinocytic entry of isolated mitochondria in epidermal growth factor
      activated human osteosarcoma cells.
AB  - Mammalian mitochondria can be transferred between cells both in culture and in
      vivo. There is evidence that isolated mitochondria enter cells by endocytosis,
      but the mechanism has not been fully characterised. We investigated the entry
      mechanism of isolated mitochondria into human osteosarcoma (HOS) cells. Initially
      we confirmed that respiratory-competent cells can be produced following
      incubation of HOS cells lacking mitochondrial DNA (mtDNA) with functional
      exogenous mitochondria and selection in a restrictive medium. Treatment of HOS
      cells with inhibitors of different endocytic pathways suggest that uptake of EGFP
      labelled mitochondria occurs via an actin-dependent endocytic pathway which is
      consistent with macropinocytosis. We later utilised time-lapse microscopy to show
      that internalised mitochondria were found in large, motile cellular vesicles.
      Finally, we used confocal imaging to show that EGFP-labelled mitochondria
      colocalise with a macropinocytic cargo molecule during internalisation, HOS cells
      produce membrane ruffles interacting with external mitochondria during uptake and
      EGFP-labelled mitochondria are found within early macropinosomes inside cells. In
      conclusion our results are consistent with isolated mitochondria being
      internalised by macropinocytosis in HOS cells.

PMID- 29018290
TI  - Mass extinctions drove increased global faunal cosmopolitanism on the
      supercontinent Pangaea.
AB  - Mass extinctions have profoundly impacted the evolution of life through not only
      reducing taxonomic diversity but also reshaping ecosystems and biogeographic
      patterns. In particular, they are considered to have driven increased
      biogeographic cosmopolitanism, but quantitative tests of this hypothesis are rare
      and have not explicitly incorporated information on evolutionary relationships.
      Here we quantify faunal cosmopolitanism using a phylogenetic network approach for
      891 terrestrial vertebrate species spanning the late Permian through Early
      Jurassic. This key interval witnessed the Permian-Triassic and Triassic-Jurassic
      mass extinctions, the onset of fragmentation of the supercontinent Pangaea, and
      the origins of dinosaurs and many modern vertebrate groups. Our results recover
      significant increases in global faunal cosmopolitanism following both mass
      extinctions, driven mainly by new, widespread taxa, leading to homogenous
      'disaster faunas'. Cosmopolitanism subsequently declines in post-recovery
      communities. These shared patterns in both biotic crises suggest that mass
      extinctions have predictable influences on animal distribution and may shed light
      on biodiversity loss in extant ecosystems.Mass extinctions are thought to produce
      'disaster faunas', communities dominated by a small number of widespread species.
      Here, Button et al. develop a phylogenetic network approach to test this
      hypothesis and find that mass extinctions did increase faunal cosmopolitanism
      across Pangaea during the late Palaeozoic and early Mesozoic.

PMID- 29018291
TI  - Multiple Geographical Origins of Environmental Sex Determination enhanced the
      diversification of Darwin's Favourite Orchids.
AB  - Environmental sex determination (ESD) - a change in sexual function during an
      individual life span driven by environmental cues - is an exceedingly rare sexual
      system among angiosperms. Because ESD can directly affect reproduction success,
      it could influence diversification rate as compared with lineages that have
      alternative reproductive systems. Here we test this hypothesis using a solid
      phylogenetic framework of Neotropical Catasetinae, the angiosperm lineage richest
      in taxa with ESD. We assess whether gains of ESD are associated with higher
      diversification rates compared to lineages with alternative systems while
      considering additional traits known to positively affect diversification rates in
      orchids. We found that ESD has evolved asynchronously three times during the last
      ~5 Myr. Lineages with ESD have consistently higher diversification rates than
      related lineages with other sexual systems. Habitat fragmentation due to mega
      wetlands extinction, and climate instability are suggested as the driving forces
      for ESD evolution.

PMID- 29018293
TI  - Off-Label Drug Bills Back on Track: But Democrats Could Run at Least One Off the
      Rails.
AB  - Off-label drug bills are back on track but could run off the rails.

PMID- 29018295
TI  - Drug and Device News.
AB  - Approvals, new indications, regulatory activities, and more.

PMID- 29018294
TI  - Misidentification of Alphanumeric Symbols Plays a Role in Errors.
AB  - Misidentification of alphanumeric symbols plays a role in errors.

PMID- 29018296
TI  - Pharmaceutical Approval Update.
AB  - L-glutamine oral powder (Endari) for reducing the acute complications of sickle
      cell disease; edaravone (Radicava) for the treatment of amyotrophic lateral
      sclerosis; and midostaurin (Rydapt) for the treatment of acute myeloid leukemia
      in combination with chemotherapy.

PMID- 29018292
TI  - The loss of P2X7 receptor expression leads to increase intestinal glucose transit
      and hepatic steatosis.
AB  - In intestinal epithelial cells (IEC), it was reported that the activation of the
      P2X7 receptor leads to the internalization of the glucose transporter GLUT2,
      which is accompanied by a reduction of IEC capacity to transport glucose. In this
      study, we used P2rx7 -/- mice to decipher P2X7 functions in intestinal glucose
      transport and to evaluate the impacts on metabolism. Immunohistochemistry
      analyses revealed the presence of GLUT2 at the apical domain of P2rx7 -/- jejunum
      enterocytes. Positron emission tomography and biodistribution studies
      demonstrated that glucose was more efficiently delivered to the circulation of
      knockout animals. These findings correlated with increase blood glucose, insulin,
      triglycerides and cholesterol levels. In fact, P2rx7 -/- mice had increased serum
      triglyceride and cholesterol levels and displayed glucose intolerance and
      resistance to insulin. Finally, P2rx7 -/- mice developed a hepatic steatosis
      characterized by a reduction of Acaca, Acacb, Fasn and Acox1 mRNA expression, as
      well as for ACC and FAS protein expression. Our study suggests that P2X7 could
      play a central role in metabolic diseases.

PMID- 29018297
TI  - Xadago (Safinamide): A Monoamine Oxidase B Inhibitor for the Adjunct Treatment of
      Motor Symptoms in Parkinson's Disease.
AB  - Xadago (safinamide), a monoamine oxidase B inhibitor for the adjunct treatment of
      motor symptoms in Parkinson's disease.

PMID- 29018298
TI  - More Clouds Form Over 340B Program: Potential Medicare Cut Underlines Need to
      Rein In Program.
AB  - In an effort to control costs, the Centers for Medicare and Medicaid Services
      wants to exact a severe reduction in reimbursement to hospitals that participate
      in the 340B Drug Pricing Program. The author discusses the program's
      shortcomings, the actions taken to address them, and how participating hospitals
      might be affected by the cut.

PMID- 29018299
TI  - Provision of Medication Therapy Management by Pharmacists to Patients With Type-2
      Diabetes Mellitus in a Federally Qualified Health Center.
AB  - BACKGROUND: Type-2 diabetes mellitus is a complex condition for which pharmacists
      are well suited to improve patient outcomes by delivering medication therapy
      management (MTM) services. When diabetes is well controlled, patients can avoid
      its long-term complications, such as cardiovascular and renal diseases. This
      article describes an MTM pilot program that was implemented at a federally
      qualified health center (FQHC). METHODS: This program was implemented at three
      clinics involving patients with uncontrolled diabetes, defined as hemoglobin A1c
      (HbA1c) greater than 8%. The primary endpoint assessed was HbA1c. Secondary
      endpoints included knowledge scores, medication adherence, and patient
      satisfaction. Outcomes were compared with a group of patients from the same
      clinics who did not receive MTM. RESULTS: Fifty-seven patients met the
      established criteria and were enrolled in the six-month program. Thirty-seven
      patients completed the program and had an average 15% reduction in HbA1c (P <
      0.05). Their average knowledge scores and medication adherence scores also
      increased from baseline. CONCLUSION: MTM provided by pharmacists as part of a
      health care team at an FQHC led to significant reductions in HbA1c.

PMID- 29018300
TI  - Vaxchora: The First FDA-Approved Cholera Vaccination in the United States.
AB  - Vaxchora is the first vaccine approved by the Food and Drug Administration for
      the prophylaxis of cholera infection. Cholera, a potentially life-threatening
      bacterial infection that occurs in the intestines and causes severe diarrhea and
      dehydration, has a low incidence in the U.S., but a high incidence in Africa,
      Southeast Asia, and other locations around the world. These areas draw travelers
      from the U.S., so cholera can present in patients who return from visits to these
      regions. Previous means of prophylaxis included the use of doxycycline for the
      prevention of traveler's diarrhea, but doxycycline is not specific for cholera.
      With the approval of Vaxchora, a live attenuated, single-dose, oral suspension
      vaccine, travelers can now visit these areas with less chance of contracting the
      bacterium Vibrio cholerae, which causes cholera infections.

PMID- 29018301
TI  - A P&T Committee's Transition to a Complete Electronic Meeting System-A Multisite
      Institution Experience.
AB  - PURPOSE: In the last few decades, changes to formulary management processes have
      taken place in institutions with closed formulary systems. However, many P&T
      committees continued to operate using traditional paper-based systems. Paper
      based systems have many limitations, including confidentiality, efficiency, open
      voting, and paper wastage. This becomes more challenging when dealing with a
      multisite P&T committee that handles formulary matters across the whole health
      care system. In this paper, we discuss the implementation of the first paperless,
      completely electronic, Web-based formulary management system across a large
      health care system in the Middle East. SUMMARY: We describe the transitioning of
      a multisite P&T committee in a large tertiary care institution from a paper-based
      to an all-electronic system. The challenges and limitations of running a
      multisite P&T committee utilizing a paper system are discussed. The design and
      development of a Web-based committee floor management application that can be
      used from notebooks, tablets, and hand-held devices is described. Implementation
      of a flexible, interactive, easy-to-use, and efficient electronic formulary
      management system is explained in detail. CONCLUSION: The development of an
      electronic P&T committee meeting system that encompasses electronic document
      sharing, voting, and communication could help multisite health care systems unify
      their formularies across multiple sites. Our experience might not be
      generalizable to all institutions because this depends heavily on system
      features, existing processes and workflow, and implementation across different
      sites.

PMID- 29018303
TI  - Research Briefs.

PMID- 29018302
TI  - Promising HIV Treatments in Late-Stage Clinical Development.
AB  - Analysts have identified several unmet needs in the HIV therapy marketplace. We
      present the promising candidates in late-stage clinical development or FDA
      review.

PMID- 29018304
TI  - The new Greiner FC-Mix tubes equal the old Terumo ones and are useful as glucose
      stabilizer after prolonged storage of samples.
AB  - INTRODUCTION: The aim of our study is to compare new Greiner tubes containing
      granulated citrate buffer with the Terumo ones and to verify if they are suitable
      for glucose stabilization after prolonged storage. MATERIALS AND METHODS: In
      Study 1, blood was collected in two Terumo and two Greiner tubes from 40 healthy
      volunteers. Samples were stored at room temperature (RT) for 1 and 2 hours,
      respectively. Comparison was made by Deming regression. In Study 2, glucose was
      measured in a reference tube (N = 50), according to the ADA-NACB guidelines and
      in aliquots of Greiner samples maintained un-centrifuged at RT for 1, 2, 4 (N =
      50) and 24, 48, 72 hours (N = 35). RESULTS: There were insignificant mixed biases
      between the Terumo and Greiner tubes. Compared to reference (5.3 mmol/L), glucose
      concentration in the new tubes was 5.4 (P < 0.05), 5.4 (P < 0.05), 5.3 (P =
      0.265), 5.2 (P = 0.156), 5.3 (P < 0.05) and 5.2 (P < 0.05) mmol/L after 1, 2, 4,
      24, 48 and 72 hours at RT, respectively. There was no biological difference
      between any of the time points up to 48 h (bias < +/- 1.95%). CONCLUSIONS: The
      study shows that the new tubes perform equally well as the Terumo ones and ensure
      glucose stabilization up to 48 h as well as permit to create a link between the
      previous studies demonstrating the clinical utility of granulated citrate buffer
      and the future ones.

PMID- 29018306
TI  - Solid Phase Deracemization of an Atropisomer.
AB  - The scope of Viedma ripening and temperature cycling with respect to chiral
      molecules has remained mostly limited to molecules with a single stereogenic
      center, while racemization proceeds through inversion at that particular
      stereocenter. In this article we demonstrate for the first time that
      atropisomers, chiral rotamers that possess an axis of chirality, can be
      successfully deracemized in the solid phase by either applying temperature
      cycling or Viedma ripening.

PMID- 29018305
TI  - Unraveling Complexity in the Solid Form Screening of a Pharmaceutical Salt: Why
      so Many Forms? Why so Few?
AB  - The solid form landscape of 5-HT2a antagonist 3-(4-(benzo[d]isoxazole-3
      yl)piperazin-1-yl)-2,2-dimethylpropanoic acid hydrochloride (B5HCl) proved
      difficult to establish. Many crystalline materials were produced by solid form
      screening, but few forms readily grew high quality crystals to afford a clear
      picture or understanding of the solid form landscape. Careful control of
      crystallization conditions, a range of experimental methods, computational
      modeling of solvate structures, and crystal structure prediction were required to
      see potential arrangements of the salt in its crystal forms. Structural diversity
      in the solid form landscape of B5HCl was apparent in the layer structures for the
      anhydrate polymorphs (Forms I and II), dihydrate and a family of solvates with
      alcohols. The alcohol solvates, which provided a distinct packing from the neat
      forms and the dihydrate, form layers with conserved hydrogen bonding between
      B5HCl and the solvent, as well as stacking of the aromatic rings. The ability of
      the alcohol hydrocarbon moieties to efficiently pack between the layers accounted
      for the difficulty in growing some solvate crystals and the inability of other
      solvates to crystallize altogether. Through a combination of experiment and
      computation, the crystallization problems, form stability, and desolvation
      pathways of B5HCl have been rationalized at a molecular level.

PMID- 29018307
TI  - Management of Citrus Canker in Argentina, a Success Story.
AB  - Citrus canker is an important bacterial disease of citrus in several regions of
      the world. Strains of Xanthomonas citri type-A (Xc-A) group are the primary
      pathogen where citrus canker occurs. After Xc-A entered the Northeast of
      Argentina in 1974, the disease spread rapidly from 1977 to 1980 and then slowed
      down and remained moving at slow pace until 1990 when it became endemic. Citrus
      canker was detected in Northwest Argentina in 2002. This paper presents the main
      steps in the fight of the disease and the management strategies that have been
      used to control citrus canker at this time. We think the process might be usefull
      to other countries with the same situation. Results from more than 40 years of
      research in Northeast (NE) Argentina indicate that we are at the limit of
      favorable environment for the disease. The severity of citrus canker is greatly
      affected by the environment and El Nino Southern Oscillation (ENSO) phenomenon
      which causes cyclic fluctuations on the disease intensity in the NE region.
      Weather-based logistic regression models adjusted to quantify disease levels in
      field conditions showed that the environmental effect was strongly modulated by
      the distance from a windbreak. Production of healthy fruits in citrus canker
      endemic areas is possible knowing the dynamics of the disease. A voluntary
      Integrated Plan to Reduce the Risk of Canker has been in place since 1994 and it
      allows growers to export unsymptomatic, uninfested fresh fruit to countries which
      are free of the disease and require healthy, pathogen free fruits. The experience
      from Argentina can be replicated in other countries after appropriate trials.

PMID- 29018308
TI  - Epidemiological Characteristics of Scab of Japanese Apricot in Korea.
AB  - Scabs caused by Venturia carpophila greatly reduce the quality of the fruits of
      the Japanese apricot (Prunus mume) when the disease is not properly managed. The
      disease produces a superficial blemish that is unlikely to affect the overall
      yield of processed fruit, but reduce the value of fruit intended for the fresh
      market. Incidence rates of scab at sprayed and unsprayed orchards range from 0%
      to 21.5% and from 30.2% to 100%, respectively, in the major cultivation regions
      of Jeonnam Province during the growing season of 2009. The trends in disease
      progress were quite similar, regardless of regions, and cultivar Namgo was
      relatively less damaged by scab compared to cultivar Cheonmae among the tested
      Japanese apricot cultivars. The fruits on branches 1.5 m above the infected
      Japanese apricot trees and the stem-end parts of the infected fruits were more
      severely damaged by scabs, possibly because of rain and run-off facilitate
      dissemination of conidia of V. carpophila and subsequent infection of the fruits
      or branches. The conidia of V. carpophila were dispersed from March 24 to April
      26 in 2010, and more conidia were dispersed from 2-year-old branches than 1-year
      old branches. Since the control efficacies were higher than 90% after more than
      two applications of Trifloxystrobin WG at 10-day-intervals from mid April, it is
      that effective fungicides be applied at least two times at 10-day-intervals from
      the middle of April to manage scabs of Japanese apricot in orchards.

PMID- 29018309
TI  - Global Transcriptome Profiling of Xanthomonas oryzae pv. oryzae under in planta
      Growth and in vitro Culture Conditions.
AB  - Xanthomonas oryzae pv. oryzae (Xoo), the causative agent of bacterial blight, is
      a major threat to rice productivity. Here, we performed RNA-Seq based
      transcriptomic analysis of Xoo transcripts isolated under in planta growth (on
      both susceptible and resistant hosts) and in vitro culture conditions. Our in
      planta extraction method resulted in successful enrichment of Xoo cells and
      provided RNA samples of high quality. A total of 4,619 differentially expressed
      genes were identified between in planta and in vitro growth conditions. The
      majority of the differentially expressed genes identified under in planta growth
      conditions were related to the nutrient transport, protease activity, stress
      tolerance, and pathogenicity. Among them, over 1,300 differentially expressed
      genes were determined to be secretory, including 184 putative type III effectors
      that may be involved in Xoo pathogenicity. Expression pattern of some of these
      identified genes were further validated by semi-quantitative RT-PCR. Taken
      together, these results provide a transcriptome overview of Xoo under in planta
      and in vitro growth conditions with a focus on its pathogenic processes,
      deepening our understanding of the behavior and pathogenicity of Xoo.

PMID- 29018310
TI  - Virus Incidence of Sweet Potato in Korea from 2011 to 2014.
AB  - A nationwide survey was performed to investigate the current incidence of viral
      diseases in Korean sweet potatoes for germplasm and growing fields from 2011 to
      2014. A total of 83.8% of the germplasm in Korea was infected with viruses in
      2011. Commercial cultivars that were used to supply growing fields were infected
      at a rate of 62.1% in 2012. Among surveyed viruses, the incidence of five
      Potyvirus species that infect sweet potato decreased between 2012 and 2013, and
      then increased again in 2014. Representatively, the incidence of Sweet potato
      feathery mottle virus (SPFMV) was 87.0% in 2012, 20.7% in 2013 and then increased
      to 35.3% in 2014. Unlike RNA viruses, DNA viruses were shown to decrease
      continuously. The incidence of Sweet potato leaf curl virus (SPLCV) was 5.5% in
      2003, 59.5% in 2011, and 47.4% in 2012. It then decreased continuously year by
      year to 33.2% in 2013, and then 25.6% in 2014. While the infection rate of each
      virus species showed a tendency to decline, the virus infection status was more
      variable in 2013 and 2014. Nevertheless, the high rate of single infections and
      mixed infection combinations were more variable than the survey results from
      2012. As shown in the results from 2013, the most prevalent virus infection was a
      single infection at 27.6%, with the highest rate of infection belonging to sweet
      potato symptomless virus-1 (SPSMV-1) (12.9%). Compared to 2013, infection
      combinations were more varied in 2014, with a total of 122 kinds of mixed
      infection.

PMID- 29018311
TI  - De novo Genome Assembly and Single Nucleotide Variations for Soybean Mosaic Virus
      Using Soybean Seed Transcriptome Data.
AB  - Soybean is the most important legume crop in the world. Several diseases in
      soybean lead to serious yield losses in major soybean-producing countries.
      Moreover, soybean can be infected by diverse viruses. Recently, we carried out a
      large-scale screening to identify viruses infecting soybean using available
      soybean transcriptome data. Of the screened transcriptomes, a soybean
      transcriptome for soybean seed development analysis contains several virus
      associated sequences. In this study, we identified five viruses, including
      soybean mosaic virus (SMV), infecting soybean by de novo transcriptome assembly
      followed by blast search. We assembled a nearly complete consensus genome
      sequence of SMV China using transcriptome data. Based on phylogenetic analysis,
      the consensus genome sequence of SMV China was closely related to SMV isolates
      from South Korea. We examined single nucleotide variations (SNVs) for SMVs in the
      soybean seed transcriptome revealing 780 SNVs, which were evenly distributed on
      the SMV genome. Four SNVs, C-U, U-C, A-G, and G-A, were frequently identified.
      This result demonstrated the quasispecies variation of the SMV genome. Taken
      together, this study carried out bioinformatics analyses to identify viruses
      using soybean transcriptome data. In addition, we demonstrated the application of
      soybean transcriptome data for virus genome assembly and SNV analysis.

PMID- 29018312
TI  - Diffusible and Volatile Antifungal Compounds Produced by an Antagonistic Bacillus
      velezensis G341 against Various Phytopathogenic Fungi.
AB  - The aim of this study was to identify volatile and agar-diffusible antifungal
      metabolites produced by Bacillus sp. G341 with strong antifungal activity against
      various phytopathogenic fungi. Strain G341 isolated from four-year-old roots of
      Korean ginseng with rot symptoms was identified as Bacillus velezensis based on
      16S rDNA and gyrA sequences. Strain G341 inhibited mycelial growth of all
      phytopathogenic fungi tested. In vivo experiment results revealed that n-butanol
      extract of fermentation broth effectively controlled the development of rice
      sheath blight, tomato gray mold, tomato late blight, wheat leaf rust, barley
      powdery mildew, and red pepper anthracnose. Two antifungal compounds were
      isolated from strain G341 and identified as bacillomycin L and fengycin A by
      MS/MS analysis. Moreover, volatile compounds emitted from strain G341 were found
      to be able to inhibit mycelial growth of various phytopathogenic fungi. Based on
      volatile compound profiles of strain G341 obtained through headspace collection
      and analysis on GC-MS, dimethylsulfoxide, 1-butanol, and 3-hydroxy-2-butanone
      (acetoin) were identified. Taken together, these results suggest that B.
      valezensis G341 can be used as a biocontrol agent for various plant diseases
      caused by phytopathogenic fungi.

PMID- 29018314
TI  - Experimental Infection of Different Tomato Genotypes with Tomato mosaic virus Led
      to a Low Viral Population Heterogeneity in the Capsid Protein Encoding Region.
AB  - The complete genome sequence of a Slovak SL-1 isolate of Tomato mosaic virus
      (ToMV) was determined from the next generation sequencing (NGS) data, further
      confirming a limited sequence divergence in this tobamovirus species. Tomato
      genotypes Monalbo, Mobaci and Moperou, respectively carrying the susceptible tm-2
      allele or the Tm-1 and Tm-2 resistant alleles, were tested for their
      susceptibility to ToMV SL-1. Although the three tomato genotypes accumulated ToMV
      SL-1 to similar amounts as judged by semi-quantitative DAS-ELISA, they showed
      variations in the rate of infection and symptomatology. Possible differences in
      the intra-isolate variability and polymorphism between viral populations
      propagating in these tomato genotypes were evaluated by analysis of the capsid
      protein (CP) encoding region. Irrespective of genotype infected, the intra
      isolate haplotype structure showed the presence of the same highly dominant CP
      sequence and the low level of population diversity (0.08-0.19%). Our results
      suggest that ToMV CP encoding sequence is relatively stable in the viral
      population during its replication in vivo and provides further demonstration that
      RNA viruses may show high sequence stability, probably as a result of purifying
      selection.

PMID- 29018313
TI  - Characterization of Bacillus amyloliquefaciens DA12 Showing Potent Antifungal
      Activity against Mycotoxigenic Fusarium Species.
AB  - In an attempt to develop a biological control agent against mycotoxigenic
      Fusarium species, we isolated Bacillus amyloliquefaciens strain DA12 from soil
      and explored its antimicrobial activities. DA12 was active against the growth of
      mycotoxigenic F. asiaticum, F. graminearum, F. proliferatum, and F.
      verticillioides both in vitro and in planta (maize). Further screening using dual
      culture extended the activity range of strain DA12 against other fungal pathogens
      including Botrytis cinerea, Colletotrichum coccodes, Endothia parasitica,
      Fusarium oxysporum, Raffaelea quercus-mongolicae, and Rhizoctonia solani. The
      butanol extract of the culture filtrate of B. amyloliquefaciens DA12 highly
      inhibited the germination of F. graminearum macroconidia with inhibition rate 83%
      at a concentration of 31.3 MUg/ml and 100% at a concentration of 250 MUg/ml. The
      antifungal metabolite from the butanol extract was identified as iturin A by thin
      layer chromatography-bioautography. In addition, volatile organic compounds
      produced by DA12 were able to inhibit mycelial growth of various phytopathogenic
      fungi. The volatile compounds were identified as 2-heptanone, 5-methyl heptanone
      and 6-methyl heptanone by gas chromatography-mass spectrometry (GC-MS) analysis.
      These results indicate that the antagonistic activity of Bacillus
      amyloliquefaciens DA12 was attributable to iturin A and volatile heptanones, and
      the strain could be used as a biocontrol agent to reduce the development of
      Fusarium diseases and mycotoxin contamination of crops.

PMID- 29018315
TI  - Characterization of a Begomovirus-Betasatellite Complex, Producing Defective
      Molecules in Spinach (Spinacia oleracea L.), a New Host for Begomovirus and
      Betasatellite Complex in Pakistan.
AB  - Spinach is a vegetable crop which is widely grown over a large area especially in
      Punjab province of Pakistan. Leaf curling and enations on spinach plant collected
      shown to be associated with the begomovirus Pedilanthus leaf curl virus (PeLCV)
      and Shahdadpur strain of Cotton leaf curl Multan betasatellite (CLCuMBSha).
      Defective molecules of half and quarter size derived from monopartite
      begomoviruses are usually generated by the deletion of virion-sense sequences.
      Characterization of defective molecules of PeLCV from spinach revealed that the
      molecules of half the size are derived from the deletion of complementary-sense
      genes while quarter size molecule appears to have evolved by further deletion.
      This is the first report of the begomovirus-betasatellite complex on spinach and
      unusual defective molecules derived from deletion of complementary-sense genes in
      Pakistan.

PMID- 29018316
TI  - Temperature and CO2 Level Influence Potato leafroll virus Infection in Solanum
      tuberosum.
AB  - We determined the effects of atmospheric temperature (10-30 +/- 2 degrees C in 5
      degrees C increments) and carbon dioxide (CO2) levels (400 +/- 50 ppm, 540 +/- 50
      ppm, and 940 +/- 50 ppm) on the infection of Solanum tuberosum cv. Chubaek by
      Potato leafroll virus (PLRV). Below CO2 levels of 400 +/- 50 ppm, the PLRV
      infection rate and RNA content in plant tissues increased as the temperature
      increased to 20 +/- 2 degrees C, but declined at higher temperatures. At high CO2
      levels (940 +/- 50 ppm), more plants were infected by PLRV at 30 +/- 2 degrees C
      than at 20 or 25 +/- 2 degrees C, whereas PLRV RNA content was unchanged in the
      20-30 +/- 2 degrees C temperature range. The effects of atmospheric CO2
      concentration on the acquisition of PLRV by Myzus persicae and accumulation of
      PLRV RNA in plant tissues were investigated using a growth chamber at 20 +/- 2
      degrees C. The M. persicae PLRV RNA content slightly increased at elevated CO2
      levels (940 +/- 50 ppm), but this increase was not statistically significant.
      Transmission rates of PLRV by Physalis floridana increased as CO2 concentration
      increased. More PLRV RNA accumulated in potato plants maintained at 540 or 940 +/
      50 ppm CO2, than in plants maintained at 400 +/- 50 ppm. This is the first
      evidence of greater PLRV RNA accumulation and larger numbers of S. tuberosum
      plants infected by PLRV under conditions of combined high CO2 levels (940 +/- 50
      ppm) and high temperature (30 +/- 2 degrees C).

PMID- 29018317
TI  - JAKE(r) Multimodal Data Capture System: Insights from an Observational Study of
      Autism Spectrum Disorder.
AB  - Objective: To test usability and optimize the Janssen Autism Knowledge Engine
      (JAKE(r)) system's components, biosensors, and procedures used for objective
      measurement of core and associated symptoms of autism spectrum disorder (ASD) in
      clinical trials. Methods: A prospective, observational study of 29 children and
      adolescents with ASD using the JAKE system was conducted at three sites in the
      United States. This study was designed to establish the feasibility of the JAKE
      system and to learn practical aspects of its implementation. In addition to
      information collected by web and mobile components, wearable biosensor data were
      collected both continuously in natural settings and periodically during a battery
      of experimental tasks administered in laboratory settings. This study is
      registered at clinicaltrials.gov, NCT02299700. Results: Feedback collected
      throughout the study allowed future refinements to be planned for all components
      of the system. The Autism Behavior Inventory (ABI), a parent-reported measure of
      ASD core and associated symptoms, performed well. Among biosensors studied, the
      eye-tracker, sleep monitor, and electrocardiogram were shown to capture high
      quality data, whereas wireless electroencephalography was difficult to use due to
      its form factor. On an exit survey, the majority of parents rated their overall
      reaction to JAKE as positive/very positive. No significant device-related events
      were reported in the study. Conclusion: The results of this study, with the
      described changes, demonstrate that the JAKE system is a viable, useful, and safe
      platform for use in clinical trials of ASD, justifying larger validation and
      deployment studies of the optimized system.

PMID- 29018318
TI  - Electrophysiological Correlates of Change Detection during Delayed Matching Task:
      A Comparison of Different References.
AB  - Detecting the changed information between memory representation and incoming
      sensory inputs is a fundamental cognitive ability. By offering the promise of
      excellent temporal resolution, event-related potential (ERP) technique has served
      as a primary tool for studying this process with reference of the linked mastoid
      (LM). However, given that LM may distort the ERP signals, it is still
      undetermined whether LM is the best reference choice. The goal of the current
      study was to systematically compare LM, reference electrode standardization
      technique (REST) and average reference (AR) for assessing the ERP correlates of
      change detection during a delayed matching task. Colored shapes were adopted as
      materials while both the task-relevant shape feature and -irrelevant color
      feature could be changed. The results of the ERP amplitude showed that both of
      the task-relevant and -conjunction feature changes elicited significantly more
      positive posterior P2 in REST and AR, but not in LM. Besides, significantly
      increased N270 was observed in task-relevant and -conjunction feature changes in
      both the REST and LM, but in the conjunction feature change in AR. Only the REST
      obtained N270 revealed a significant increment in task-irrelevant feature change,
      which was compatible with the delayed behavioral performance. Statistical
      parametric scalp mapping (SPSM) results showed a left posterior distribution for
      AR, an anterior distribution for LM, and both the anterior and left posterior
      distributions for REST. These results indicate that different types of references
      may provide distinct cognitive interpretations. Interestingly, only the SPSM of
      REST was consistent with previous fMRI findings. Combined with the evidence of
      simulation studies and the current observations, we take the REST-based results
      as the objective one, and recommend using REST technology in the future ERP data
      analysis.

PMID- 29018319
TI  - On the Value of Estimating Human Arm Stiffness during Virtual Teleoperation with
      Robotic Manipulators.
AB  - Teleoperated robotic systems are widely spreading in multiple different fields,
      from hazardous environments exploration to surgery. In teleoperation, users
      directly manipulate a master device to achieve task execution at the slave robot
      side; this interaction is fundamental to guarantee both system stability and task
      execution performance. In this work, we propose a non-disruptive method to study
      the arm endpoint stiffness. We evaluate how users exploit the kinetic redundancy
      of the arm to achieve stability and precision during the execution of different
      tasks with different master devices. Four users were asked to perform two planar
      trajectories following virtual tasks using both a serial and a parallel link
      master device. Users' arm kinematics and muscular activation were acquired and
      combined with a user-specific musculoskeletal model to estimate the joint
      stiffness. Using the arm kinematic Jacobian, the arm end-point stiffness was
      derived. The proposed non-disruptive method is capable of estimating the arm
      endpoint stiffness during the execution of virtual teleoperated tasks. The
      obtained results are in accordance with the existing literature in human motor
      control and show, throughout the tested trajectory, a modulation of the arm
      endpoint stiffness that is affected by task characteristics and hand speed and
      acceleration.

PMID- 29018320
TI  - Virtual Balancing for Studying and Training Postural Control.
AB  - Postural control during free stance has been frequently interpreted in terms of
      balancing an inverted pendulum. This even holds, if subjects do not balance their
      own, but an external body weight. We introduce here a virtual balancing
      apparatus, which produces torque in the ankle joint as a function of ankle angle
      resembling the gravity and inertial effects of free standing. As a first aim of
      this study, we systematically modified gravity, damping, and inertia to examine
      its effect on postural control beyond the physical constraints given in the real
      world. As a second aim, we compared virtual balancing to free stance to test its
      suitability for balance training in patients who are not able to balance their
      full body weight due to certain medical conditions. In a feasibility study, we
      analyzed postural control during free stance and virtual balancing in 15 healthy
      subjects. Postural control was characterized by spontaneous sway measures and
      measures of perturbed stance. During free stance, perturbations were induced by
      pseudorandom anterior-posterior tilts of the body support surface. In the virtual
      balancing task, we systematically varied the anterior-posterior position of the
      foot plate where the balancing forces are zero following a similar pseudorandom
      stimulus profile. We found that subjects' behavior during virtual balancing
      resembles free stance on a tilting platform. This specifically holds for the
      profile of body excursions as a function of stimulus frequencies. Moreover, non
      linearity between stimulus and response amplitude is similar in free and virtual
      balancing. The overall larger stimulus induced body excursions together with an
      altered phase behavior between stimulus and response could be in part explained
      by the limited use of vestibular and visual feedback in our experimental setting.
      Varying gravity or damping significantly affected postural behavior. Inertia as
      an isolated factor had a mild effect on the response functions. We conclude that
      virtual balancing may be well suited to simulate conditions which could otherwise
      only be realized in space experiments or during parabolic flights. Further
      studies are needed to examine patients' potential benefit of virtual balance
      training.

PMID- 29018322
TI  - Editorial: Advanced Neuroimaging Methods for Studying Autism Disorder.

PMID- 29018321
TI  - Lateralization of Executive Function: Working Memory Advantage for Same Hemifield
      Stimuli in the Monkey.
AB  - Working memory capacity, the amount of information that may be maintained in mind
      over a period of seconds, is extremely limited, to a handful of items. Some
      evidence exists that the number of visual items that may be maintained in working
      memory is independent for the two hemifields. To test this idea, we trained
      monkeys to perform visual working memory tasks that required maintenance in
      memory of the locations and/or shapes of 3-5 visual stimuli. We then tested
      whether systematic performance differences were present for stimuli concentrated
      in the same hemifield, vs. distributed across hemifields. We found little
      evidence to support the expectation that working memory capacity is independent
      in the two hemifields. Instead, when an advantage of stimulus arrangement was
      present, it involved multiple stimuli presented in the same hemifield. This
      conclusion was consistent across variations of the task, performance levels, and
      apparent strategies adopted by individual subjects. This result suggests that
      factors such as grouping that favor processing of stimuli in relative proximity
      may counteract the benefits of independent processing in the two hemispheres. Our
      results reveal an important property of working memory and place constraints on
      models of working memory capacity.

PMID- 29018323
TI  - Cerebrospinal Fluid Amino Acid Profiling of Pediatric Cases with Tuberculous
      Meningitis.
AB  - Background: In Africa, tuberculosis is generally regarded as persisting as one of
      the most devastating infectious diseases. The pediatric population is
      particularly vulnerable, with infection of the brain in the form of tuberculous
      meningitis (TBM) being the most severe manifestation. TBM is often difficult to
      diagnose in its early stages because of its non-specific clinical presentation.
      Of particular concern is that late diagnosis, and subsequent delayed treatment,
      leads to high risk of long-term neurological sequelae, and even death. Using
      advanced technology and scientific expertise, we are intent on further describing
      the biochemistry behind this devastating neuroinflammatory disease, with the goal
      of improving upon its early diagnosis. Method: We used the highly sensitive
      analytical platform of gas chromatography-mass spectrometry (GC-MS) to analyze
      amino acid profiles of cerebrospinal fluid (CSF) collected from a cohort of 33
      South African pediatric TBM cases, compared to 34 controls. Results: Through the
      use of a stringent quality assurance procedure and various statistical
      techniques, we were able to confidently identify five amino acids as being
      significantly elevated in TBM cases, namely, alanine, asparagine, glycine,
      lysine, and proline. We found also in an earlier untargeted metabolomics
      investigation that alanine can be attributed to increased CSF lactate levels, and
      lysine as a marker of lipid peroxidation. Alanine, like glycine, is an inhibitory
      neurotransmitter in the brain. Asparagine, as with proline, is linked to the
      glutamate-glutamine cycle. Asparagine is associated with the removal of increased
      nitrites in the brain, whereas elevated proline coincides with the classic
      biochemical marker of increased CSF protein in TBM. All five discriminatory amino
      acids are linked to ammonia due to increased nitrites in TBM. Conclusion: A large
      amount of untapped biochemical information is present in CSF of TBM cases, of
      which amino acid profiling through GC-MS has potential in aiding in earlier
      diagnosis, and hence crucial earlier treatment.

PMID- 29018325
TI  - Hearing Loss Controlled by Optogenetic Stimulation of Nonexcitable Nonglial Cells
      in the Cochlea of the Inner Ear.
AB  - Light-gated ion channels and transporters have been applied to a broad array of
      excitable cells including neurons, cardiac myocytes, skeletal muscle cells and
      pancreatic beta-cells in an organism to clarify their physiological and
      pathological roles. Nonetheless, among nonexcitable cells, only glial cells have
      been studied in vivo by this approach. Here, by optogenetic stimulation of a
      different nonexcitable cell type in the cochlea of the inner ear, we induce and
      control hearing loss. To our knowledge, deafness animal models using optogenetics
      have not yet been established. Analysis of transgenic mice expressing
      channelrhodopsin-2 (ChR2) induced by an oligodendrocyte-specific promoter
      identified this channel in nonglial cells-melanocytes-of an epithelial-like
      tissue in the cochlea. The membrane potential of these cells underlies a highly
      positive potential in a K+-rich extracellular solution, endolymph; this
      electrical property is essential for hearing. Illumination of the cochlea to
      activate ChR2 and depolarize the melanocytes significantly impaired hearing
      within a few minutes, accompanied by a reduction in the endolymphatic potential.
      After cessation of the illumination, the hearing thresholds and potential
      returned to baseline during several minutes. These responses were replicable
      multiple times. ChR2 was also expressed in cochlear glial cells surrounding the
      neuronal components, but slight neural activation caused by the optical
      stimulation was unlikely to be involved in the hearing impairment. The acute
      onset, reversible and repeatable phenotype, which is inaccessible to conventional
      gene-targeting and pharmacological approaches, seems to at least partially
      resemble the symptom in a population of patients with sensorineural hearing loss.
      Taken together, this mouse line may not only broaden applications of optogenetics
      but also contribute to the progress of translational research on deafness.

PMID- 29018324
TI  - Design and Characterization of a Human Monoclonal Antibody that Modulates Mutant
      Connexin 26 Hemichannels Implicated in Deafness and Skin Disorders.
AB  - Background: Mutations leading to changes in properties, regulation, or expression
      of connexin-made channels have been implicated in 28 distinct human hereditary
      diseases. Eight of these result from variants of connexin 26 (Cx26), a protein
      critically involved in cell-cell signaling in the inner ear and skin. Lack of non
      toxic drugs with defined mechanisms of action poses a serious obstacle to
      therapeutic interventions for diseases caused by mutant connexins. In particular,
      molecules that specifically modulate connexin hemichannel function without
      affecting gap junction channels are considered of primary importance for the
      study of connexin hemichannel role in physiological as well as pathological
      conditions. Monoclonal antibodies developed in the last three decades have become
      the most important class of therapeutic biologicals. Recombinant methods permit
      rapid selection and improvement of monoclonal antibodies from libraries with
      large diversity. Methods: By screening a combinatorial library of human single
      chain fragment variable (scFv) antibodies expressed in phage, we identified a
      candidate that binds an extracellular epitope of Cx26. We characterized antibody
      action using a variety of biochemical and biophysical assays in HeLa cells,
      organotypic cultures of mouse cochlea and human keratinocyte-derived cells.
      Results: We determined that the antibody is a remarkably efficient, non-toxic,
      and completely reversible inhibitor of hemichannels formed by connexin 26 and
      does not affect direct cell-cell communication via gap junction channels.
      Importantly, we also demonstrate that the antibody efficiently inhibits
      hyperative mutant Cx26 hemichannels implicated in autosomal dominant non
      syndromic hearing impairment accompanied by keratitis and hystrix-like ichthyosis
      deafness (KID/HID) syndrome. We solved the crystal structure of the antibody,
      identified residues that are critical for binding and used molecular dynamics to
      uncover its mechanism of action. Conclusions: Although further studies will be
      necessary to validate the effect of the antibody in vivo, the methodology
      described here can be extended to select antibodies against hemichannels composed
      by other connexin isoforms and, consequently, to target other pathologies
      associated with hyperactive hemichannels. Our study highlights the potential of
      this approach and identifies connexins as therapeutic targets addressable by
      screening phage display libraries expressing human randomized antibodies.

PMID- 29018326
TI  - The Molecular Fingerprint of Dorsal Root and Trigeminal Ganglion Neurons.
AB  - The dorsal root ganglia (DRG) and trigeminal ganglia (TG) are clusters of cell
      bodies of highly specialized sensory neurons which are responsible for relaying
      information about our environment to the central nervous system. Despite previous
      efforts to characterize sensory neurons at the molecular level, it is still
      unknown whether those present in DRG and TG have distinct expression profiles and
      therefore a unique molecular fingerprint. To address this question, we isolated
      lumbar DRG and TG neurons using fluorescence-activated cell sorting from Advillin
      GFP transgenic mice and performed RNA sequencing. Our transcriptome analyses
      showed that, despite being overwhelmingly similar, a number of genes are
      differentially expressed in DRG and TG neurons. Importantly, we identified 24
      genes which were uniquely expressed in either ganglia, including an arginine
      vasopressin receptor and several homeobox genes, giving each population a
      distinct molecular fingerprint. We compared our findings with published studies
      to reveal that many genes previously reported to be present in neurons are in
      fact likely to originate from other cell types in the ganglia. Additionally, our
      neuron-specific results aligned well with a dataset examining whole human TG and
      DRG. We propose that the data can both improve our understanding of primary
      afferent biology and help contribute to the development of drug treatments and
      gene therapies which seek targets with unique or restricted expression patterns.

PMID- 29018327
TI  - Maternal Cigarette Smoke Exposure Worsens Neurological Outcomes in Adolescent
      Offspring with Hypoxic-Ischemic Injury.
AB  - Hypoxic-ischemic (HI) encephalopathy occurs in approximately 6 per 1000 term
      newborns leading to devastating neurological consequences, such as cerebral palsy
      and seizures. Maternal smoking is one of the prominent risk factors contributing
      to HI injury. Mitochondrial integrity plays a critical role in neural injury and
      repair during HI. We previously showed that maternal cigarette smoke exposure
      (SE) can reduce brain mitochondrial fission and autophagosome markers in male
      offspring. This was accompanied by increased brain cell apoptosis (active caspase
      3) and DNA fragmentation (TUNEL staining). Here, we aimed to investigate whether
      maternal SE leads to more severe neurological damage after HI brain injury in
      male offspring. Female BALB/c mice (8 weeks) were exposed to cigarette smoke
      prior to mating, during gestation, and lactation. At postnatal day 10, half of
      the pups from each litter underwent left carotid artery occlusion, followed by
      exposure to 8% oxygen (92% nitrogen). At postnatal day 40-44, maternal SE reduced
      grip strength in grip traction and foot fault tests, which were also reduced by
      HI injury to similar levels regardless of the maternal group. Limb coordination
      was impaired by maternal SE which was not worsened by HI injury. Maternal SE
      increased anxiety level in the offspring, which was normalized by HI injury.
      Apoptosis markers were increased in different brain regions by maternal SE, with
      the cortex having further increased TUNEL by HI injury, along with increased
      markers of inflammation and mitophagy. We conclude that maternal SE can worsen HI
      induced cellular damage in male offspring well into adolescence.

PMID- 29018328
TI  - Intermittent Ethanol during Adolescence Leads to Lasting Behavioral Changes in
      Adulthood and Alters Gene Expression and Histone Methylation in the PFC.
AB  - Adolescents primarily consume alcohol in binges, which can be particularly
      harmful to the developing frontal cortex and increase risk for an adult alcohol
      use disorder. We conducted a study investigating immediate and long lasting
      changes to the prefrontal cortex (PFC) transcriptome to determine the molecular
      mechanisms underlying adult ethanol behavioral sensitivity following binge
      ethanol in adolescence. DBA/2J mice were orally dosed with 4 g/kg ethanol
      intermittently from day 29 to 42. Adolescent mice were tested for anxiety-like
      behavior and ethanol sensitivity using the loss of righting reflex task. As
      adults, mice were tested for cognitive changes using the novel object recognition
      task, ethanol-induced anxiolysis and ethanol sensitivity. Adolescent binge
      ethanol altered ethanol sensitivity in young mice and led to lasting memory
      deficits in the object recognition test and greater ethanol sensitivity in
      adulthood. Using genomic profiling of transcripts in the PFC, we found that binge
      ethanol reduced myelin-related gene expression and altered chromatin modifying
      genes involved in histone demethylation at H3K9 and H3K36. We hypothesize that
      ethanol's actions on histone methylation may be a switch for future
      transcriptional changes that underlie the behavioral changes lasting into
      adulthood.

PMID- 29018329
TI  - CDDO and ATRA Instigate Differentiation of IMR32 Human Neuroblastoma Cells.
AB  - Neuroblastoma is the most common solid extra cranial tumor in infants. Improving
      the clinical outcome of children with aggressive tumors undergoing one of the
      multiple treatment options has been a major concern. Differentiating
      neuroblastoma cells holds promise in inducing tumor growth arrest and treating
      minimal residual disease. In this study, we investigated the effect of partial
      PPARgamma agonist 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) on
      human neuroblastoma IMR32 cells. Our results demonstrate that treatment with low
      concentration of CDDO and particularly in combination with all trans retinoic
      acid (ATRA) induced neurite outgrowth, increased the percentage of more than two
      neurites bearing cells, and decreased viability in IMR32 cells. These
      morphological changes were associated with an increase in expression of bonafide
      differentiation markers like beta3-tubulin and Neuron Specific Enolase (NSE). The
      differentiation was accompanied by a decrease in the expression of MYCN whose
      amplification is known to contribute to the pathogenesis of neuroblastoma. MYCN
      is known to negatively regulate NMYC downstream-regulated gene 1 (NDRG1) in
      neuroblastomas. MYCN down-regulation induced by CDDO correlated with increased
      expression of NDRG1. CDDO decreased Anaplastic Lymphoma Kinase (ALK) mRNA
      expression without affecting its protein level, while ATRA significantly down
      regulated ALK. Antagonism of PPARgamma receptor by T0070907 meddled with
      differentiation inducing effects of CDDO as observed by stunted neurite growth,
      increased viability and decreased expression of differentiation markers. Our
      findings indicate that IMR32 differentiation induced by CDDO in combination with
      ATRA enhances, differentiation followed by cell death via cAMP-response-element
      binding protein (CREB) independent and PPARgamma dependent signaling mechanisms.

PMID- 29018330
TI  - MicroRNA-210 Protects PC-12 Cells Against Hypoxia-Induced Injury by Targeting
      BNIP3.
AB  - MicroRNA (miR)-210 is the most consistently and predominantly up-regulated miR in
      response to hypoxia in multiple cancer cells. The roles of miR-210 in rat adrenal
      gland pheochromocytoma (PC-12) cells remain unknown. We aimed to explore the
      possible effect of miR-210 in neonatal brain injury. We explored the potential
      molecular mechanism by using PC-12 cells under hypoxia. Scramble miRs, miR-210
      mimic, miR-210 inhibitor or its negative control were respectively transfected
      into PC-12 cells. Cell viability, migration, invasion and apoptosis were also
      assessed to evaluate hypoxia-induced cell injury. The expression level of miR-210
      was identified by quantitative real-time polymerase chain reaction (qRT-PCR)
      analysis. Apoptosis-related protein expression as well as key kinases in the
      phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR)
      signal pathway was studied by Western blot analysis. Hypoxia suppressed cell
      viability, migration and invasion, but promoted apoptosis through activation of
      mitochondrial- and caspase-dependent pathways. Hypoxia markedly induced up
      regulation of miR-210 in PC-12 cells. Overexpression of miR-210 protected PC-12
      cells against hypoxia-induced injury. Bcl-2 adenovirus E1B 19 kDa-interacting
      protein 3 (BNIP3) was proven to be a target gene of miR-210 in PC-12 cells. miR
      210 overexpression ameliorated the hypoxia-induced injury in PC-12 cells by down
      regulating BNIP3. Hypoxia-induced alterations of key kinases in the PI3K/AKT/mTOR
      signal pathway were affected by aberrant expression of BNIP3. These findings
      suggested that miR-210 protected PC-12 cells against hypoxia-induced injury by
      targeting BNIP3, involving the PI3K/AKT/mTOR signal pathway.

PMID- 29018331
TI  - Distinctive Roles for alpha7*- and alpha9*-Nicotinic Acetylcholine Receptors in
      Inflammatory and Autoimmune Responses in the Murine Experimental Autoimmune
      Encephalomyelitis Model of Multiple Sclerosis.
AB  - Previous studies have demonstrated immunosuppressive and anti-inflammatory
      effects of nicotine, including in the experimental autoimmune encephalomyelitis
      (EAE) model in mice of some forms of multiple sclerosis (MS). Other studies using
      knock-out (KO) mice have implicated nicotinic acetylcholine (ACh) receptors
      containing alpha7, alpha9, or beta2 subunits (alpha7*-, alpha9*- or beta2*-nAChR)
      in different, disease-exacerbating or disease-ameliorating processes. These
      outcomes are in harmony with gene expression analyses showing nAChR subunit mRNA
      in many classes of immune system cell types. Consistent with influences on
      disease status, predictable effects of nAChR subunit (and subtype) KO, or of
      nicotine exposure, are seen on immune cell numbers and distribution and on
      cytokine levels or other markers of immunity, inflammation, demyelination, and
      axonal degradation. Providing support for our hypotheses about distinctive roles
      for nAChR subtypes in EAE, here we have used direct and adoptive EAE induction
      and a nAChR subunit gene double knock-out (DKO) strategy. Immune cell expression
      of nAChR alpha9 subunits as protein is demonstrated by immunostaining of isolated
      CD4+, CD8+, CD11b+ and CD11c+ cells from wild-type (WT) mice, but not in cells
      from nAChR alpha9 subunit KO animals. Nicotine exposure is protective against
      directly-induced EAE in WT or alpha7/alpha9 DKO animals relative to effects seen
      in WT/vehicle-treated mice, but, remarkably, EAE is exacerbated in vehicle
      treated alpha7/alpha9 DKO mice. Brain lesion volume and intra-cranial
      inflammatory activity similarly are higher in DKO/vehicle than in WT/vehicle
      treated animals, although nicotine's protective effects are seen in each
      instance. By contrast, in adoptive transfer studies, disease severity is
      attenuated and disease onset is delayed in recipients of splenocytes from WT
      animals treated with nicotine rather than with vehicle. Moreover, protection as
      seen in nicotine-treated WT animals is the same in recipients of splenocytes from
      nAChR alpha7/alpha9 DKO mice irrespective of their exposure to nicotine or
      vehicle. When combined with previous observations, these findings are consistent
      with disease exacerbation (or even induction) being mediated at least in part via
      alpha9*-nAChR in peripheral immune cells. They also suggest protective roles of
      central nervous system (CNS) alpha7*-nAChR. The results suggest that both alpha7*
      and alpha9*-nAChR are potential targets of therapeutic ligands to modulate
      inflammation and autoimmunity.

PMID- 29018332
TI  - The Beneficial Effects of Melatonin Administration Following Hypoxia-Ischemia in
      Preterm Fetal Sheep.
AB  - Melatonin (MLT) is an endogenous hormone that controls circadian cycle. MLT has
      additional important properties that make it appealing as a neuroprotective agent
      it is a potent anti-oxidant, with anti-apoptotic and anti-inflammatory
      properties. MLT is safe for administration during pregnancy or to the newborn
      after birth, and can reduce white matter brain injury under conditions of chronic
      fetal hypoxia. Accordingly, in the current study, we examined whether an
      intermediate dose of MLT could restore white matter brain development when
      administered after an acute hypoxic ischemic (HI) insult in preterm fetal sheep.
      Fifteen fetal sheep at 95-98 days gestation were instrumented with femoral artery
      and vein catheters, and a silastic cuff placed around the umbilical cord. At 102
      days gestation, the cuff was inflated, causing complete umbilical cord occlusion
      for 25 min in 10 fetuses, to induce acute severe HI. Five HI fetuses received
      intravenous MLT for 24 h beginning at 2 h after HI. The remaining five fetuses
      were administered saline alone. Ten days after HI, the fetal brain was collected
      from each animal and white and gray matter neuropathology assessed. HI caused a
      significant increase in apoptotic cell death (TUNEL+), activated microglia (Iba
      1+), and oxidative stress (8-OHdG+) within the subventricular and subcortical
      white matter. HI reduced the total number of oligodendrocytes and CNPase+ myelin
      density. MLT administration following HI decreased apoptosis, inflammation and
      oxidative stress within the white matter. MLT had intermediate benefits for the
      developing white matter: it increased oligodendrocyte cell number within the
      periventricular white matter only, and improved CNPase+ myelin density within the
      subcortical but not the striatal white matter. MLT administration following HI
      was also associated with improved neuronal survival within the cortex.
      Neuropathology in preterm infants is complex and mediated by multiple mechanisms,
      including inflammation, oxidative stress and apoptotic pathways. Treatment with
      MLT presents a safe approach to neuroprotective therapy in preterm infants but
      appears to have brain region-specific benefits within the white matter.

PMID- 29018337
TI  - Editorial: Self-Organization in the Nervous System.

PMID- 29018335
TI  - A Connectomic Analysis of the Human Basal Ganglia Network.
AB  - The current model of basal ganglia circuits has been introduced almost two
      decades ago and has settled the basis for our understanding of basal ganglia
      physiology and movement disorders. Although many questions are yet to be
      answered, several efforts have been recently made to shed new light on basal
      ganglia function. The traditional concept of "direct" and "indirect" pathways,
      obtained from axonal tracing studies in non-human primates and post-mortem fiber
      dissection in the human brain, still retains a remarkable appeal but is somehow
      obsolete. Therefore, a better comprehension of human structural basal ganglia
      connectivity in vivo, in humans, is of uttermost importance given the involvement
      of these deep brain structures in many motor and non-motor functions as well as
      in the pathophysiology of several movement disorders. By using diffusion magnetic
      resonance imaging and tractography, we have recently challenged the traditional
      model of basal ganglia network by showing the possible existence, in the human
      brain, of cortico-pallidal, cortico-nigral projections, which could be mono- or
      polysynaptic, and an extensive subcortical network connecting the cerebellum and
      basal ganglia. Herein, we aimed at reconstructing the basal ganglia connectome
      providing a quantitative connectivity analysis of the reconstructed pathways. The
      present findings reinforce the idea of an intricate, not yet unraveled, network
      involving the cerebral cortex, basal ganglia, and cerebellum. Our findings may
      pave the way for a more comprehensive and holistic pathophysiological model of
      basal ganglia circuits.

PMID- 29018333
TI  - Cadherin-13 Deficiency Increases Dorsal Raphe 5-HT Neuron Density and Prefrontal
      Cortex Innervation in the Mouse Brain.
AB  - Background: During early prenatal stages of brain development, serotonin (5-HT)
      specific neurons migrate through somal translocation to form the raphe nuclei and
      subsequently begin to project to their target regions. The rostral cluster of
      cells, comprising the median and dorsal raphe (DR), innervates anterior regions
      of the brain, including the prefrontal cortex. Differential analysis of the mouse
      5-HT system transcriptome identified enrichment of cell adhesion molecules in 5
      HT neurons of the DR. One of these molecules, cadherin-13 (Cdh13) has been shown
      to play a role in cell migration, axon pathfinding, and synaptogenesis. This
      study aimed to investigate the contribution of Cdh13 to the development of the
      murine brain 5-HT system. Methods: For detection of Cdh13 and components of the 5
      HT system at different embryonic developmental stages of the mouse brain, we
      employed immunofluorescence protocols and imaging techniques, including
      epifluorescence, confocal and structured illumination microscopy. The consequence
      of CDH13 loss-of-function mutations on brain 5-HT system development was explored
      in a mouse model of Cdh13 deficiency. Results: Our data show that in murine
      embryonic brain Cdh13 is strongly expressed on 5-HT specific neurons of the DR
      and in radial glial cells (RGCs), which are critically involved in regulation of
      neuronal migration. We observed that 5-HT neurons are intertwined with these
      RGCs, suggesting that these neurons undergo RGC-guided migration. Cdh13 is
      present at points of intersection between these two cell types. Compared to
      wildtype controls, Cdh13-deficient mice display increased cell densities in the
      DR at embryonic stages E13.5, E17.5, and adulthood, and higher serotonergic
      innervation of the prefrontal cortex at E17.5. Conclusion: Our findings provide
      evidence for a role of CDH13 in the development of the serotonergic system in
      early embryonic stages. Specifically, we indicate that Cdh13 deficiency affects
      the cell density of the developing DR and the posterior innervation of the
      prefrontal cortex (PFC), and therefore might be involved in the migration, axonal
      outgrowth and terminal target finding of DR 5-HT neurons. Dysregulation of CDH13
      expression may thus contribute to alterations in this system of
      neurotransmission, impacting cognitive function, which is frequently impaired in
      neurodevelopmental disorders including attention-deficit/hyperactivity and autism
      spectrum disorders.

PMID- 29018336
TI  - Encoding and Decoding Models in Cognitive Electrophysiology.
AB  - Cognitive neuroscience has seen rapid growth in the size and complexity of data
      recorded from the human brain as well as in the computational tools available to
      analyze this data. This data explosion has resulted in an increased use of
      multivariate, model-based methods for asking neuroscience questions, allowing
      scientists to investigate multiple hypotheses with a single dataset, to use
      complex, time-varying stimuli, and to study the human brain under more
      naturalistic conditions. These tools come in the form of "Encoding" models, in
      which stimulus features are used to model brain activity, and "Decoding" models,
      in which neural features are used to generated a stimulus output. Here we review
      the current state of encoding and decoding models in cognitive electrophysiology
      and provide a practical guide toward conducting experiments and analyses in this
      emerging field. Our examples focus on using linear models in the study of human
      language and audition. We show how to calculate auditory receptive fields from
      natural sounds as well as how to decode neural recordings to predict speech. The
      paper aims to be a useful tutorial to these approaches, and a practical
      introduction to using machine learning and applied statistics to build models of
      neural activity. The data analytic approaches we discuss may also be applied to
      other sensory modalities, motor systems, and cognitive systems, and we cover some
      examples in these areas. In addition, a collection of Jupyter notebooks is
      publicly available as a complement to the material covered in this paper,
      providing code examples and tutorials for predictive modeling in python. The aim
      is to provide a practical understanding of predictive modeling of human brain
      data and to propose best-practices in conducting these analyses.

PMID- 29018338
TI  - Altered Distant Synchronization of Background Network in Mild Cognitive
      Impairment during an Executive Function Task.
AB  - Few studies to date have investigated the background network in the cognitive
      state relying on executive function in mild cognitive impairment (MCI) patients.
      Using the index of degree of centrality (DC), we explored distant synchronization
      of background network in MCI during a hybrid delayed-match-to-sample task (DMST),
      which mainly relies on the working memory component of executive function. We
      observed significant interactions between group and cognitive state in the
      bilateral posterior cingulate cortex (PCC) and the ventral subregion of
      precuneus. For normal control (NC) group, the long distance functional
      connectivity (FC) of the PCC/precuneus with the other regions of the brain was
      higher in rest state than that working memory state. For MCI patients, however,
      this pattern altered. There was no significant difference between rest and
      working memory state. The similar pattern was observed in the other cluster
      located in the right angular gyrus. To examine whether abnormal DC in
      PCC/precuneus and angular gyrus partially resulted from the deficit of FC between
      these regions and the other parts in the whole brain, we conducted a seed-based
      correlation analysis with these regions as seeds. The results indicated that the
      FC between bilateral PCC/precuneus and the right inferior parietal lobule (IPL)
      increased from rest to working memory state for NC participants. For MCI
      patients, however, there was no significant change between rest and working
      memory state. The similar pattern was observed for the FC between right angular
      gyrus and right anterior insula. However, there was no difference between MCI and
      NC groups in global efficiency and modularity. It may indicate a lack of
      efficient reorganization from rest state to a working memory state in the brain
      network of MCI patients. The present study demonstrates the altered distant
      synchronization of background network in MCI during a task relying on executive
      function. The results provide a new perspective regarding the neural mechanisms
      of executive function deficits in MCI patients, and extend our understanding of
      brain patterns in task-evoked cognitive states.

PMID- 29018340
TI  - Impaired Spatial Memory and Enhanced Habit Memory in a Rat Model of Post
      traumatic Stress Disorder.
AB  - High levels of emotional arousal can impair spatial memory mediated by the
      hippocampus, and enhance stimulus-response (S-R) habit memory mediated by the
      dorsolateral striatum (DLS). The present study was conducted to determine whether
      these memory systems may be similarly affected in an animal model of post
      traumatic stress disorder (PTSD). Sprague-Dawley rats were subjected to a "single
      prolonged stress" (SPS) procedure and 1 week later received training in one of
      two distinct versions of the plus-maze: a hippocampus-dependent place learning
      task or a DLS-dependent response learning task. Results indicated that, relative
      to non-stressed control rats, SPS rats displayed slower acquisition in the place
      learning task and faster acquisition in the response learning task. In addition,
      extinction of place learning and response learning was impaired in rats exposed
      to SPS, relative to non-stressed controls. The influence of SPS on hippocampal
      spatial memory and DLS habit memory observed in the present study may be relevant
      to understanding some common features of PTSD, including hippocampal memory
      deficits, habit-like avoidance responses to trauma-related stimuli, and greater
      likelihood of developing drug addiction and alcoholism.

PMID- 29018339
TI  - Gravitational and Dynamic Components of Muscle Torque Underlie Tonic and Phasic
      Muscle Activity during Goal-Directed Reaching.
AB  - Human reaching movements require complex muscle activations to produce the forces
      necessary to move the limb in a controlled manner. How gravity and the complex
      kinetic properties of the limb contribute to the generation of the muscle
      activation pattern by the central nervous system (CNS) is a long-standing and
      controversial question in neuroscience. To tackle this issue, muscle activity is
      often subdivided into static and phasic components. The former corresponds to
      posture maintenance and transitions between postures. The latter corresponds to
      active movement production and the compensation for the kinetic properties of the
      limb. In the present study, we improved the methodology for this subdivision of
      muscle activity into static and phasic components by relating them to joint
      torques. Ten healthy subjects pointed in virtual reality to visual targets
      arranged to create a standard center-out reaching task in three dimensions.
      Muscle activity and motion capture data were synchronously collected during the
      movements. The motion capture data were used to calculate postural and dynamic
      components of active muscle torques using a dynamic model of the arm with 5
      degrees of freedom. Principal Component Analysis (PCA) was then applied to muscle
      activity and the torque components, separately, to reduce the dimensionality of
      the data. Muscle activity was also reconstructed from gravitational and dynamic
      torque components. Results show that the postural and dynamic components of
      muscle torque represent a significant amount of variance in muscle activity. This
      method could be used to define static and phasic components of muscle activity
      using muscle torques.

PMID- 29018334
TI  - Cornu Ammonis Regions-Antecedents of Cortical Layers?
AB  - Studying neocortex and hippocampus in parallel, we are struck by the
      similarities. All three to four layered allocortices and the six layered
      mammalian neocortex arise in the pallium. All receive and integrate multiple
      cortical and subcortical inputs, provide multiple outputs and include an array of
      neuronal classes. During development, each cell positions itself to sample
      appropriate local and distant inputs and to innervate appropriate targets.
      Simpler cortices had already solved the need to transform multiple coincident
      inputs into serviceable outputs before neocortex appeared in mammals. Why then do
      phylogenetically more recent cortices need multiple pyramidal cell layers? A
      simple answer is that more neurones can compute more complex functions. The
      dentate gyrus and hippocampal CA regions-which might be seen as hippocampal
      antecedents of neocortical layers-lie side by side, albeit around a tight bend.
      Were the millions of cells of rat neocortex arranged in like fashion, the surface
      area of the CA pyramidal cell layers would be some 40 times larger. Even if
      evolution had managed to fold this immense sheet into the space available, the
      distances between neurones that needed to be synaptically connected would be huge
      and to maintain the speed of information transfer, massive, myelinated fiber
      tracts would be needed. How much more practical to stack the "cells that fire and
      wire together" into narrow columns, while retaining the mechanisms underlying the
      extraordinary precision with which circuits form. This demonstrably efficient
      arrangement presents us with challenges, however, not the least being to
      categorize the baffling array of neuronal subtypes in each of five "pyramidal
      layers." If we imagine the puzzle posed by this bewildering jumble of apical
      dendrites, basal dendrites and axons, from many different pyramidal and
      interneuronal classes, that is encountered by a late-arriving interneurone
      insinuating itself into a functional circuit, we can perhaps begin to understand
      why definitive classification, covering every aspect of each neurone's structure
      and function, is such a challenge. Here, we summarize and compare the development
      of these two cortices, the properties of their neurones, the circuits they form
      and the ordered, unidirectional flow of information from one hippocampal region,
      or one neocortical layer, to another.

PMID- 29018342
TI  - Negative Facial Expressions - But Not Visual Scenes - Enhance Human Working
      Memory in Younger and Older Participants.
AB  - Many studies have investigated the influence of emotion on memory processes
      across the human lifespan. Some results have shown older adults (OA) performing
      better with positive stimuli, some with negative items, whereas some found no
      impact of emotional valence. Here we tested, in two independent studies, how
      younger adults (YA) and OA would perform in a visuospatial working memory (VSWM)
      task with positive, negative, and neutral images. The task consisted of
      identifying the new location of a stimulus in a crescent set of identical stimuli
      presented in different locations in a touch-screen monitor. In other words,
      participants should memorize the locations previously occupied to identify the
      new location. For each trial, the number of occupied locations increased until 8
      or until a mistake was made. In study 1, 56 YA and 38 OA completed the task using
      images from the International Affective Picture System (IAPS). Results showed
      that, although YA outperformed OA, no effects of emotion were found. In study 2,
      26 YA and 25 OA were tested using facial expressions as stimuli. Data from this
      study showed that negative faces facilitated performance and this effect did not
      differ between age groups. No differences were found between men and women. Taken
      together, our findings suggest that YA and OA's VSWM can be influenced by the
      emotional valence of the information, though this effect was present only for
      facial stimuli. Presumably, this may have happened due to the social and
      biological importance of such stimuli, which are more effective in transmitting
      emotions than IAPS images. Critically, our results also indicate that the mixed
      findings in the literature about the influence of aging on the interactions
      between memory and emotion may be caused by the use of different stimuli and
      methods. This possibility should be kept in mind in future studies about memory
      and emotion across the lifespan.

PMID- 29018343
TI  - Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of
      Dexlansoprazole Injection in Chinese Subjects.
AB  - Background: Not all patients with acid-related disorders receiving proton pump
      inhibitor (PP) treatment get adequate gastric pH control. The genetic variation
      of receptors, metabolic enzymes, and transporters are known to cause failures of
      therapies. We have conducted a study to evaluate the influence of gastric H+/K+
      ATPase, CYP2C19, and ABCB1 polymorphisms on the pharmacokinetic and
      pharmacodynamic profiles of dexlansoprazole injection in healthy Chinese
      subjects. Methods: A total of 51 subjects were enrolled for pharmacokinetic and
      pharmacodynamic study after a single intravenous administration of 20 or 30 mg
      dexlansoprazole. Plasma concentrations were determined using a chiral liquid
      chromatography-mass spectrometry method. The intragastric pH and baseline
      adjusted intragastric pH parameters were introduced to evaluate the
      pharmacodynamic characters. Genotyping was performed by polymerase chain
      reaction. Results: The pharmacokinetic parameters were significantly influenced
      by CYP2C19 phenotypes, and gastric acid secretion inhibition were affected by
      both gastric H+/K+-ATPase and CYP2C19 polymorphisms. Gastric H+/K+-ATPase
      genotypes had greater effects than CYP2C19 genotypes on the suppression of
      gastric acid secretion. Conclusion: Gastric H+/K+-ATPase polymorphism may be one
      of the main reasons that cause insufficient gastric acid inhibition.

PMID- 29018344
TI  - Xanthates As Useful Probes for Testing the Active Sites of Cytochromes P450 4A11
      and 2E1.
AB  - Xanthates (alkyl or aryl derivatives of dithiocarbonic acid) have been shown to
      be selective mechanism-based inactivators of cytochromes P450 2B1/2B6 and 2E1 due
      to covalent binding of a reactive intermediate to apoprotein after double
      hydrogen abstraction at alpha-carbon atom, suggesting interaction of the xanthate
      dithiocarbonic head with the enzyme heme. The structures of xanthates with a long
      alkyl chain are similar to the fatty acids. Saturated fatty acids (FA) such as
      lauric acid (LA), are metabolized by different cytochrome P450 isoforms to omega-
      and (omega-1)-hydroxy products, in humans done by CYP4A11 and CYP2E1,
      respectively. In the present study we aimed at elucidating the possible
      interactions of xanthates with two cytochrome P450 isoforms CYP4A11 and CYP2E1
      involved in the metabolism of the FA. Our experiments showed that LA-omega
      hydroxylation by CYP4A11 is inhibited in a competitive manner by xanthates with
      long alkyl chain (C12-xanthate being the most potent inhibitor). On the other
      hand LA-(omega-1)-hydroxylation reaction by purified CYP2E1 is inactivated by a
      mechanism-based type. The suggested differences in the interactions of C12
      xanthate with the two cytochrome P450 isoforms were investigated by molecular
      modeling using docking approach. The results suggested that in CYP2E1 active site
      C12-xanthate coordinates to the heme with its most vulnerable dithiocarbonic head
      leading to a mechanism-based inactivation. In CYP4A11 xanthate alkyl chain is
      exposed to the heme, thus, a potenial omega-hydroxylated xanthate product could
      be formed, which could inhibit in a competitive manner the hydroxylation of LA.
      The observed differences of xanthates interactions with the active sites of the
      two similar cytochrome P450 isoforms (CYP4A11 and CYP2E1) involved in the
      metabolism of FA, which lead to different changes in the enzyme activity, suggest
      that xanthates can be used as probing tools for analyzing enzyme active sites
      when exploring useful and selective compounds influencing FA homeostasis.

PMID- 29018341
TI  - Recent Development of Hydrogen Sulfide Releasing/Stimulating Reagents and Their
      Potential Applications in Cancer and Glycometabolic Disorders.
AB  - As an important endogenous gaseous signaling molecule, hydrogen sulfide (H2S)
      exerts various effects in the body. A variety of pathological changes, such as
      cancer, glycometabolic disorders, and diabetes, are associated with altered
      endogenous levels of H2S, especially decreased. Therefore, the supplement of H2S
      is of great significance for the treatment of diseases containing the above
      pathological changes. At present, many efforts have been made to increase the in
      vivo levels of H2S by administration of gaseous H2S, simple inorganic sulfide
      salts, sophisticated synthetic slow-releasing controllable H2S donors or
      materials, and using H2S stimulating agents. In this article, we reviewed the
      recent development of H2S releasing/stimulating reagents and their potential
      applications in two common pathological processes including cancer and
      glycometabolic disorders.

PMID- 29018346
TI  - Comparative Analysis of Compatibility Effects on Invigorating Blood Circulation
      for Cyperi Rhizoma Series of Herb Pairs Using Untargeted Metabolomics.
AB  - The mutual-assistance compatibility of Cyperi Rhizoma (Xiangfu, XF) and Angelicae
      Sinensis Radix (Danggui, DG), Chuanxiong Rhizoma (Chuanxiong, CX), Paeoniae Radix
      Alba (Baishao, BS), or Corydalis Rhizoma (Yanhusuo, YH), found in a traditional
      Chinese medicine (TCM) named Xiang-Fu-Si-Wu Decoction (XFSWD), can produce
      synergistic and promoting blood effects. Nowadays, XFSWD has been proved to be
      effective in activating blood circulation and dissipating blood stasis. However,
      the role of the herb pairs synergistic effects in the formula were poorly
      understood. In order to quantitatively assess the compatibility effects of herb
      pairs, mass spectrometry-based untargeted metabolomics studies were performed.
      The plasma and urine metabolic profiles of acute blood stasis rats induced by
      adrenaline hydrochloride and ice water and administered with Cyperi Rhizoma
      Angelicae Sinensis Radix (XD), Cyperi Rhizoma-Chuanxiong Rhizoma (XC), Cyperi
      Rhizoma-Paeoniae Radix Alba (XB), Cyperi Rhizoma-Corydalis Rhizoma (XY) were
      compared. Relative peak area of identified metabolites was calculated and
      principal component analysis (PCA) score plot from the potential markers was used
      to visualize the overall differences. Then, the metabolites results were used
      with biochemistry indicators and genes expression values as parameters to
      quantitatively evaluate the compatibility effects of XF series of herb pairs by
      PCA and correlation analysis. The collective results indicated that the four XF
      herb pairs regulated glycerophospholipid metabolism, steroid hormone biosynthesis
      and arachidonic acid metabolism pathway. XD was more prominent in regulating the
      blood stasis during the four XF herb pairs. This study demonstrated that
      metabolomics was a useful tool to efficacy evaluation and compatibility effects
      of TCM elucidation.

PMID- 29018345
TI  - Involvement of PPARgamma in the Anticonvulsant Activity of EP-80317, a Ghrelin
      Receptor Antagonist.
AB  - Ghrelin, des-acyl ghrelin and other related peptides possess anticonvulsant
      activities. Although ghrelin and cognate peptides were shown to physiologically
      regulate only the ghrelin receptor, some of them were pharmacologically proved to
      activate the peroxisome proliferator-activated receptor gamma (PPARgamma) through
      stimulation of the scavenger receptor CD36 in macrophages. In our study, we
      challenged the hypothesis that PPARgamma could be involved in the anticonvulsant
      effects of EP-80317, a ghrelin receptor antagonist. For this purpose, we used the
      PPARgamma antagonist GW9662 to evaluate the modulation of EP-80317 anticonvulsant
      properties in two different models. Firstly, the anticonvulsant effects of EP
      80317 were studied in rats treated with pilocarpine to induce status epilepticus
      (SE). Secondly, the anticonvulsant activity of EP-80317 was ascertained in the
      repeated 6-Hz corneal stimulation model in mice. Behavioral and video
      electrocorticographic (ECoG) analyses were performed in both models. We also
      characterized levels of immunoreactivity for PPARgamma in the hippocampus of 6-Hz
      corneally stimulated mice. EP-80317 predictably antagonized seizures in both
      models. Pretreatment with GW9662 counteracted almost all EP-80317 effects both in
      mice and rats. Only the effects of EP-80317 on power spectra of ECoGs recorded
      during repeated 6-Hz corneal stimulation were practically unaffected by GW9662
      administration. Moreover, GW9662 alone produced a decrease in the latency of
      tonic-clonic seizures and accelerated the onset of SE in rats. Finally, in the
      hippocampus of mice treated with EP-80317 we found increased levels of PPARgamma
      immunoreactivity. Overall, these results support the hypothesis that PPARgamma is
      able to modulate seizures and mediates the anticonvulsant effects of EP-80317.

PMID- 29018347
TI  - Mechanisms of the Testis Toxicity Induced by Chronic Exposure to Mequindox.
AB  - Mequindox (MEQ) is a synthetic antimicrobial agent widely used in China since the
      1980s. Although the toxicity of MEQ is well recognized, its testis toxicity has
      not been adequately investigated. In the present study, we provide evidence that
      MEQ triggers oxidative stress, mitochondrion dysfunction and spermatogenesis
      deficiency in mice after exposure to MEQ (0, 25, 55, and 110 mg/kg in the diet)
      for up to 18 months. The genotoxicity and adrenal toxicity may contribute to
      sperm abnormalities caused by MEQ. Moreover, using LC/MS-IT-TOF analysis, two
      metabolites, 3-methyl-2-(1-hydroxyethyl) quinoxaline-N4-monoxide (M4) and 3
      methyl-2-(1-hydroxyethyl) quinoxaline-N1-monoxide (M8), were detected in the
      serum of mice, which directly confirms the relationship between the N->O group
      reduction metabolism of MEQ and oxidative stress. Interestingly, only M4 was
      detected in the testes, suggesting that the higher reproductive toxicity of M4
      than M8 might be due to the increased stability of M4-radical (M4-R) compared to
      M8-radical (M8-R). Furthermore, the expression of the blood-testis barrier (BTB)
      associated junctions such as tight junctions, gap junctions and basal ectoplasmic
      specializations were also examined. The present study demonstrated for the first
      time the role of the M4 in testis toxicity, and illustrated that the oxidative
      stress, mitochondrion dysfunction and interference in spermatogenesis, as well as
      the altered expression of BTB related junctions, were involved in the
      reproductive toxicity mediated by MEQ in vivo.

PMID- 29018348
TI  - Target Identification of Mycobacterium tuberculosis Phenotypic Hits Using a
      Concerted Chemogenomic, Biophysical, and Structural Approach.
AB  - Mycobacterium phenotypic hits are a good reservoir for new chemotypes for the
      treatment of tuberculosis. However, the absence of defined molecular targets and
      modes of action could lead to failure in drug development. Therefore, a
      combination of ligand-based and structure-based chemogenomic approaches followed
      by biophysical and biochemical validation have been used to identify targets for
      Mycobacterium tuberculosis phenotypic hits. Our approach identified EthR and InhA
      as targets for several hits, with some showing dual activity against these
      proteins. From the 35 predicted EthR inhibitors, eight exhibited an IC50 below 50
      MUM against M. tuberculosis EthR and three were confirmed to be also
      simultaneously active against InhA. Further hit validation was performed using X
      ray crystallography yielding eight new crystal structures of EthR inhibitors.
      Although the EthR inhibitors attain their activity against M. tuberculosis by
      hitting yet undefined targets, these results provide new lead compounds that
      could be further developed to be used to potentiate the effect of EthA activated
      pro-drugs, such as ethionamide, thus enhancing their bactericidal effect.

PMID- 29018350
TI  - Folliculin Interacts with Rab35 to Regulate EGF-Induced EGFR Degradation.
AB  - Aims and Hypothesis: This study aims to investigate the mechanism involved in
      intracellular regulation of EGFR degradation induced by EGF. Methods:
      Phosphorylation of proteins related to EGFR signaling was examined by western
      blot analysis. Activation, connection between Rab35 and folliculin (FLCN) were
      assessed by pulldown, coimmunoprecipitation assays separately. The relationship
      between FLCN and cell growth was detected using gene overexpression and knock
      down techniques. Results: Here, we demonstrate that interfering with FLCN, a
      tumor suppressor, reduces the rate of EGF-induced EGFR degradation, resulting in
      prolonged activation of downstream signaling. Rab35 is also involved in these
      processes. Moreover, C-terminal of FLCN binds to and activates Rab35. Of special
      interest is the observation that erlotinib, a selective EGFR inhibitor, not only
      obstructs the EGFR-mediated cellular signaling, but also abolishes EGF-stimulated
      EGFR degradation. Further results reveal that EGF facilitates the activation of
      Rab35, and FLCN modulates EGF-dependent Rab35 activation and cell growth.
      Conclusions: Taken together, our study proposes a negative-feedback regulation
      model in which FLCN mediates EGF-induced Rab35 activation, thereby increasing
      EGFR degradation and attenuating EGFR signaling.

PMID- 29018351
TI  - Upper-Body Muscular Endurance Training Improves Performance Following 50 min of
      Double Poling in Well-Trained Cross-Country Skiers.
AB  - This study investigated the effect of muscular endurance training on O2-cost and
      performance in double poling (DP) on a rollerski treadmill. Twenty-two well
      trained cross-country skiers (31 +/- 4 years, 77 +/- 9 kg, 181 +/- 8 cm, VO2max
      running: 64 +/- 5 mL.kg-1.min-1) were counter-balanced to either a combined
      muscular endurance and running interval training group [MET; n = 11 (? = 9, ? =
      2)], or an endurance running interval training group [ET; n = 11 (? = 9, ? = 2)].
      Both groups continued their normal low-and moderate intensity training, but
      replaced 2 weekly high intensity-training sessions with two project-specific
      sessions for 6 weeks. In these sessions, MET combined upper-body muscular
      endurance training (4 * 30 repetitions, 90 s rest between sets) and running
      intervals (3 * 4 or 2 * 6 min, 3 min rest), while ET performed running intervals
      only (6 * 4 or 4 * 6 min, 3 min rest). The DP test-protocol consisted of 50 min
      submaximal poling for O2-cost measurement, followed by a self-paced 1,000-m
      performance test. In addition, subjects performed a VO2max test in running. MET
      increased muscular endurance (P < 0.05) and 1RM in simulated DP (P < 0.01) more
      than ET. Further, MET reduced the 1,000-m time and O2-cost compared to baseline
      values (P < 0.05), and tended to improve the 1,000-m time more than ET (P =
      0.06). There were no changes in VO2max running or VO2peak DP in either MET or ET.
      In conclusion, 6 weeks of muscular endurance training increased both muscular
      endurance and 1RM in simulated DP. Further, specific upper-body muscular
      endurance training improved DP performance and thus, seems as a promising
      training model to optimize performance in well-trained cross-country skiers.

PMID- 29018352
TI  - How Nonlinear-Type Time-Frequency Analysis Can Help in Sensing Instantaneous
      Heart Rate and Instantaneous Respiratory Rate from Photoplethysmography in a
      Reliable Way.
AB  - Despite the population of the noninvasive, economic, comfortable, and easy-to
      install photoplethysmography (PPG), it is still lacking a mathematically rigorous
      and stable algorithm which is able to simultaneously extract from a single
      channel PPG signal the instantaneous heart rate (IHR) and the instantaneous
      respiratory rate (IRR). In this paper, a novel algorithm called deppG is provided
      to tackle this challenge. deppG is composed of two theoretically solid nonlinear
      type time-frequency analyses techniques, the de-shape short time Fourier
      transform and the synchrosqueezing transform, which allows us to extract the
      instantaneous physiological information from the PPG signal in a reliable way. To
      test its performance, in addition to validating the algorithm by a simulated
      signal and discussing the meaning of "instantaneous," the algorithm is applied to
      two publicly available batch databases, the Capnobase and the ICASSP 2015 signal
      processing cup. The former contains PPG signals relative to spontaneous or
      controlled breathing in static patients, and the latter is made up of PPG signals
      collected from subjects doing intense physical activities. The accuracies of the
      estimated IHR and IRR are compared with the ones obtained by other methods, and
      represent the state-of-the-art in this field of research. The results suggest the
      potential of deppG to extract instantaneous physiological information from a
      signal acquired from widely available wearable devices, even when a subject
      carries out intense physical activities.

PMID- 29018353
TI  - Heat Stress Reduces Sperm Motility via Activation of Glycogen Synthase Kinase
      3alpha and Inhibition of Mitochondrial Protein Import.
AB  - The adverse effects of high environmental temperature exposure on animal
      reproductive functions have been concerned for many decades. However, the
      molecular basis of heat stress (HS)-induced decrease of sperm motility has not
      been entirely elucidated. We hypothesized that the deteriorate effects of HS may
      be mediated by damage of mitochondrial function and ATP synthesis. To test this
      hypothesis, we use mature boar sperm as model to explore the impacts of HS on
      mitochondrial function and sperm motility. A 6 h exposure to 42 degrees C (HS)
      induced significant decrease in sperm progressive motility. Concurrently, HS
      induced mitochondrial dysfunction that is indicated by decreased of membrane
      potential, respiratory chain complex I and IV activities and adenosine
      triphosphate (ATP) contents. Exogenous ATP abolished this effect suggesting that
      reduced of ATP synthesis is the committed step in HS-induced reduction of sperm
      motility. At the molecular level, the mitochondrial protein contents were
      significantly decreased in HS sperm. Notably, the cytochrome c oxidase subunit 4,
      which was synthesized in cytoplasm and translocated into mitochondria, was
      significantly lower in mitochondria of HS sperm. Glycogen synthase kinase-3alpha
      (GSK3alpha), a negative regulator of sperm motility that is inactivated by Ser21
      phosphorylation, was dephosphorylated after HS. The GSK3alpha inhibitor CHIR99021
      was able to abolish the effects of HS on sperm and their mitochondria. Taken
      together, our results demonstrate that HS affects sperm motility through
      downregulation of mitochondrial activity and ATP synthesis yield, which involves
      dephosphorylation of GSK3alpha and interference of mitochondrial remodeling.

PMID- 29018349
TI  - The Role of Hydrogen Sulfide on Cardiovascular Homeostasis: An Overview with
      Update on Immunomodulation.
AB  - Hydrogen sulfide (H2S), the third endogenous gaseous signaling molecule alongside
      nitric oxide (NO) and carbon monoxide, is synthesized by multiple enzymes in
      cardiovascular system. Similar to other gaseous mediators, H2S has demonstrated a
      variety of biological activities, including anti-oxidative, anti-apoptotic, pro
      angiogenic, vasodilating capacities and endothelial NO synthase modulating
      activity, and regulates a wide range of pathophysiological processes in
      cardiovascular disorders. However, the underlying mechanisms by which H2S
      mediates cardiovascular homeostasis are not fully understood. This review focuses
      on the recent progress on functional and mechanistic aspects of H2S in the
      inflammatory and immunoregulatory processes of cardiovascular disorders,
      importantly myocardial ischemia, heart failure, and atherosclerosis. Moreover, we
      highlight the challenges for developing H2S-based therapy to modulate the
      pathological processes in cardiovascular diseases. A better understanding of the
      immunomodulatory and biochemical functions of H2S might provide new therapeutic
      strategies for these cardiovascular diseases.

PMID- 29018355
TI  - Criterion-Validity of Commercially Available Physical Activity Tracker to
      Estimate Step Count, Covered Distance and Energy Expenditure during Sports
      Conditions.
AB  - Background: In the past years, there was an increasing development of physical
      activity tracker (Wearables). For recreational people, testing of these devices
      under walking or light jogging conditions might be sufficient. For (elite)
      athletes, however, scientific trustworthiness needs to be given for a broad
      spectrum of velocities or even fast changes in velocities reflecting the demands
      of the sport. Therefore, the aim was to evaluate the validity of eleven Wearables
      for monitoring step count, covered distance and energy expenditure (EE) under
      laboratory conditions with different constant and varying velocities. Methods:
      Twenty healthy sport students (10 men, 10 women) performed a running protocol
      consisting of four 5 min stages of different constant velocities (4.3; 7.2; 10.1;
      13.0 km.h-1), a 5 min period of intermittent velocity, and a 2.4 km outdoor run
      (10.1 km.h-1) while wearing eleven different Wearables (Bodymedia Sensewear,
      Beurer AS 80, Polar Loop, Garmin Vivofit, Garmin Vivosmart, Garmin Vivoactive,
      Garmin Forerunner 920XT, Fitbit Charge, Fitbit Charge HR, Xaomi MiBand, Withings
      Pulse Ox). Step count, covered distance, and EE were evaluated by comparing each
      Wearable with a criterion method (Optogait system and manual counting for step
      count, treadmill for covered distance and indirect calorimetry for EE). Results:
      All Wearables, except Bodymedia Sensewear, Polar Loop, and Beurer AS80, revealed
      good validity (small MAPE, good ICC) for all constant and varying velocities for
      monitoring step count. For covered distance, all Wearables showed a very low ICC
      (<0.1) and high MAPE (up to 50%), revealing no good validity. The measurement of
      EE was acceptable for the Garmin, Fitbit and Withings Wearables (small to
      moderate MAPE), while Bodymedia Sensewear, Polar Loop, and Beurer AS80 showed a
      high MAPE up to 56% for all test conditions. Conclusion: In our study, most
      Wearables provide an acceptable level of validity for step counts at different
      constant and intermittent running velocities reflecting sports conditions.
      However, the covered distance, as well as the EE could not be assessed validly
      with the investigated Wearables. Consequently, covered distance and EE should not
      be monitored with the presented Wearables, in sport specific conditions.

PMID- 29018354
TI  - N-acetylcysteine Counteracts Adipose Tissue Macrophage Infiltration and Insulin
      Resistance Elicited by Advanced Glycated Albumin in Healthy Rats.
AB  - Background: Advanced glycation endproducts elicit inflammation. However, their
      role in adipocyte macrophage infiltration and in the development of insulin
      resistance, especially in the absence of the deleterious biochemical pathways
      that coexist in diabetes mellitus, remains unknown. We investigated the effect of
      chronic administration of advanced glycated albumin (AGE-albumin) in healthy
      rats, associated or not with N-acetylcysteine (NAC) treatment, on insulin
      sensitivity, adipose tissue transcriptome and macrophage infiltration and
      polarization. Methods: Male Wistar rats were intraperitoneally injected with
      control (C) or AGE-albumin alone, or, together with NAC in the drinking water.
      Biochemical parameters, lipid peroxidation, gene expression and protein contents
      were, respectively, determined by enzymatic techniques, reactive thiobarbituric
      acid substances, RT-qPCR and immunohistochemistry or immunoblot.
      Carboxymethyllysine (CML) and pyrraline (PYR) were determined by LC/mass
      spectrometry (LC-MS/MS) and ELISA. Results: CML and PYR were higher in AGE
      albumin as compared to C. Food consumption, body weight, systolic blood pressure,
      plasma lipids, glucose, hepatic and renal function, adipose tissue relative
      weight and adipocyte number were similar among groups. In AGE-treated animals,
      insulin resistance, adipose macrophage infiltration and Col12a1 mRNA were
      increased with no changes in M1 and M2 phenotypes as compared to C-albumin
      treated rats. Total GLUT4 content was reduced by AGE-albumin as compared to C
      albumin. NAC improved insulin sensitivity, reduced urine TBARS, adipose
      macrophage number and Itgam and Mrc mRNA and increased Slc2a4 and Ppara. CD11b,
      CD206, Ager, Ddost, Cd36, Nfkb1, Il6, Tnf, Adipoq, Retn, Arg, and Il12
      expressions were similar among groups. Conclusions: AGE-albumin sensitizes
      adipose tissue to inflammation due to macrophage infiltration and reduces GLUT4,
      contributing to insulin resistance in healthy rats. NAC antagonizes AGE-albumin
      and prevents insulin resistance. Therefore, it may be a useful tool in the
      prevention of AGE action on insulin resistance and long-term complications of DM.

PMID- 29018356
TI  - Xiao-Yao-San, a Chinese Medicine Formula, Ameliorates Chronic Unpredictable Mild
      Stress Induced Polycystic Ovary in Rat.
AB  - Chronic stress induces endocrine disturbance, which contributes to the
      development of polycystic ovary syndrome (PCOS), a condition that remains a
      challenge for clinicians to cope with. The present study investigated the effect
      of Xiao-Yao-San (XYS), a traditional Chinese medicine formula used for treatment
      of gynecological disease, on the chronic stress-induced polycystic ovary and its
      underlying mechanism. Female Sprague-Dwaley rats underwent a 3 weeks chronic
      unpredictable mild stress (CUMS) procedure to establish the PCOS model, followed
      by 4 weeks treatment with XYS (0.505 g/kg or 1.01 g/kg) by gavage. Granulosa
      cells were exposed to noradrenaline (1 mM) in vitro for 24 h, followed by
      incubation with or without XYS-treated rat serum for 24 h. Post-treatment with
      XYS ameliorated CUMS-induced irregular estrous cycles and follicles development
      abnormalities, decrease of estradiol and progesterone level as well as increase
      of luteinizing hormone in serum, reduced cystic follicles formation and the
      apoptosis and autophagy of granulosa cells, attenuated the increase in dopamine
      beta hydroxylase and c-fos level in locus coeruleus, the noradrenaline level in
      serum and ovarian tissue, and the expression of beta 2 adrenergic receptor in
      ovarian tissue. Besides, XYS alleviated the reduction of phosphorylation of
      ribosomal protein S6 kinase polypeptide I and protein kinase B, as well as the
      increase of microtubule-associated protein light chain 3-I to microtubule
      associated protein light chain 3-II conversion both in vivo and in vitro. This
      study demonstrated XYS as a potential strategy for CUMS induced polycystic ovary,
      and suggested that the beneficial role of XYS was correlated with the regulation
      of the sympathetic nerve activity.

PMID- 29018357
TI  - Distinct Subfamilies of Odorant Binding Proteins in Locust (Orthoptera,
      Acrididae): Molecular Evolution, Structural Variation, and Sensilla-Specific
      Expression.
AB  - Odorant binding proteins (OBPs) play an important role in insect olfaction,
      facilitating transportation of odorant molecules in the sensillum lymph. While
      most of the researches are concentrated on Lepidopteran and Dipteran species, our
      knowledge about Orthopteran species is still very limited. In this study, we have
      investigated OBPs of the desert locust Schistocerca gregaria, a representative
      Orthopteran species. We have identified 14 transcripts from a S. gregaria
      antennal transcriptome encoding SgreOBPs, and recapitulated the phylogenetic
      relationship of SgreOBPs together with OBPs from three other locust species. Two
      conserved subfamilies of classic OBPs have been identified, named I-A and II-A,
      exhibiting both common and subfamily-specific amino acid motifs. Distinct
      evolutionary features were observed for subfamily I-A and II-A OBPs. Surface
      topology and interior cavity were elucidated for OBP members from the two
      subfamilies. Antennal topographic expression revealed distinct sensilla- and
      cellular- specific expression patterns for SgreOBPs from subfamily I-A and II-A.
      These findings give first insight into the repertoire of locust OBPs with respect
      to their molecular and evolutionary features as well as their expression in the
      antenna, which may serve as an initial step to unravel specific roles of distinct
      OBP subfamilies in locust olfaction.

PMID- 29018359
TI  - That Escalated Quickly-Planning to Ignore RPE Can Backfire.
AB  - Ratings of perceived exertion (RPE) are routinely assessed in exercise science
      and RPE is substantially associated with physiological criterion measures.
      According to the psychobiological model of endurance, RPE is a central limiting
      factor in performance. While RPE is known to be affected by psychological
      manipulations, it remains to be examined whether RPE can be self-regulated during
      static muscular endurance exercises to enhance performance. In this experiment,
      we investigate the effectiveness of the widely used and recommended self
      regulation strategy of if-then planning (i.e., implementation intentions) in down
      regulating RPE and improving performance in a static muscular endurance task. 62
      female students (age: M = 23.7 years, SD = 4.0) were randomly assigned to an
      implementation intention or a control condition and performed a static muscular
      endurance task. They held two intertwined rings as long as possible while
      avoiding contacts between the rings. In the implementation intention condition,
      participants had an if-then plan: "If the task becomes too strenuous for me, then
      I ignore the strain and tell myself: Keep going!" Every 25 +/- 10 s participants
      reported their RPE along with their perceived pain. Endurance performance was
      measured as time to failure, along with contact errors as a measure of
      performance quality. No differences emerged between implementation intention and
      control participants regarding time to failure and performance quality. However,
      mixed-effects model analyses revealed a significant Time-to-Failure * Condition
      interaction for RPE. Compared to the control condition, participants in the
      implementation intention condition reported substantially greater increases in
      RPE during the second half of the task and reached higher total values of RPE
      before task termination. A similar but weaker pattern evinced for perceived pain.
      Our results demonstrate that RPE during an endurance task can be self-regulated
      with if-then plans. This finding is particularly important given how frequently
      RPE is used in exercise science as a correlate of physiological processes that
      ultimately limit performance. Unexpectedly, participants with implementation
      intentions reported higher RPE than control participants. This suggests that
      strategies to self-regulate RPE might have ironic effects that hamper
      performance, maybe by increasing attention to RPE. This implication is important
      for exercise physiologists, athletes and coaches.

PMID- 29018358
TI  - Identification and Characterization of Odorant Binding Proteins in the Forelegs
      of Adelphocoris lineolatus (Goeze).
AB  - The chemosensory system is essential for insects to detect exogenous compounds,
      and odorant binding proteins (OBPs) play crucial roles in odorant binding and
      transduction. In the alfalfa plant bug Adelphocoris lineolatus, an important pest
      of multiple crops, our understanding of the physiological roles of antenna-biased
      OBPs has increased dramatically, whereas OBPs related to gustation have remained
      mostly unexplored. In this study, we employed RNA sequencing and RACE PCR methods
      to identify putative OBPs from the adult forelegs of both sexes. Eight candidate
      OBPs were identified, and three OBPs (AlinOBP15, 16, and 17) were novel. Full
      length sequence alignment and phylogenetic analyses suggested that these three
      candidate OBPs had characteristics typical of the insect OBP family. AlinOBP16
      and 17 displayed six highly conserved cysteines, placing them in the classic OBP
      subfamily, whereas AlinOBP15 resembled AlinOBP14 and clustered with the Plus-C
      clade. Quantitative real-time PCR (qRT-PCR) revealed distinct and significant
      tissue- and sex-biased expression patterns. AlinOBP15 was highly expressed in
      female heads, and AlinOBP16 and 17 were strongly expressed in female antennae. In
      particular, AlinOBP11, the most abundant OBP gene in our foreleg transcriptome
      dataset, was predominately expressed in adult legs. Furthermore, four types of
      sensilla hairs were observed on the forelegs of adult A. lineolatus, including
      sensilla trichodea, setae, and two types of sensilla chaetica (Sch1 and Sch2).
      Anti-AlinOBP11 antiserum strongly labeled the outer sensillum lymph of Sch2,
      implying that it has important gustatory functions in A. lineolatus. Our current
      findings provide evidence that OBPs can be functionally expressed in the tarsal
      gustatory sensilla of hemipteran mirid species, broadening our understanding of
      OBP chemosensory function in insects and facilitating the discovery of new
      functional targets for the regulation of insect host-searching behaviors.

PMID- 29018361
TI  - New Methods for Processing and Quantifying VO2 Kinetics to Steady State: VO2
      Onset Kinetics.
AB  - Current methods of oxygen uptake (VO2) kinetics data handling may be too
      simplistic for the complex physiology involved in the underlying physiological
      processes. Therefore, the aim of this study was to quantify the VO2 kinetics to
      steady state across the full range of sub-ventilatory threshold work rates, with
      a particular focus on the VO2 onset kinetics. Ten healthy, moderately trained
      males participated in five bouts of cycling. Each bout involved 10 min at a
      percentage of the subject's ventilation threshold (30, 45, 60, 75, 90%) from
      unloaded cycling. The VO2 kinetics was quantified using the conventional mono
      exponential time constant (tau, tau), as well as the new methods for VO2 onset
      kinetics. Compared to linear modeling, non-linear modeling caused a deterioration
      of goodness of fit (main effect, p < 0.001) across all exercise intensities.
      Remainder kinetics were also improved using a modified application of the mono
      exponential model (main effect, p < 0.001). Interestingly, the slope from the
      linear regression of the onset kinetics data is similar across all subjects and
      absolute exercise intensities, and thereby independent of subject fitness and
      tau. This could indicate that there are no functional limitations between
      subjects during this onset phase, with limitations occurring for the latter
      transition to steady state. Finally, the continuing use of mono-exponential
      modeling could mask important underlying physiology of more instantaneous VO2
      responses to steady state. Consequently, further research should be conducted on
      this new approach to VO2 onset kinetics.

PMID- 29018362
TI  - Effects of Unloaded vs. Loaded Plyometrics on Speed and Power Performance of
      Elite Young Soccer Players.
AB  - The purpose of this study was to investigate the effects of loaded and unloaded
      plyometric training strategies on speed and power performance of elite young
      soccer players. Twenty-three under-17 male soccer players (age: 15.9 +/- 1.2
      years, height: 178.3 +/- 8.1 cm, body-mass (BM): 68.1 +/- 9.3 kg) from the same
      club took part in this study. The athletes were pair-matched in two training
      groups: loaded vertical and horizontal jumps using an haltere type handheld with
      a load of 8% of the athletes' body mass (LJ; n = 12) and unloaded vertical and
      horizontal plyometrics (UJ; n = 11). Sprinting speeds at 5-, 10-, and 20-m, mean
      propulsive power (MPP) relative to the players' BM in the jump squat exercise,
      and performance in the squat jump (SJ) and countermovement jump (CMJ) were
      assessed pre- and post-training period. During the experimental period, soccer
      players performed 12 plyometric training sessions across a 6-week preseason
      period. Magnitude based inferences and standardized differences were used for
      statistical analysis. A very likely increase in the vertical jumps was observed
      for the LJ group (99/01/00 and 98/02/00 for SJ and CMJ, respectively). In the UJ
      group a likely increase was observed for both vertical jumps (83/16/01 and
      90/10/00, for SJ and CMJ, respectively). An almost certainly decrease in the
      sprinting velocities along the 20-m course were found in the LJ group (00/00/100
      for all split distances tested). Meanwhile, in the UJ likely to very likely
      decreases were observed for all sprinting velocities tested (03/18/79, 01/13/86,
      and 00/04/96, for velocities in 5-, 10-, and 20-m, respectively). No meaningful
      differences were observed for the MPP in either training group (11/85/04 and
      37/55/08 for LJ and UJ, respectively). In summary, under-17 professional soccer
      players increased jumping ability after a 6-week preseason training program,
      using loaded or unloaded jumps. Despite these positive adaptations, both
      plyometric strategies failed to produce worthwhile improvements in maximal speed
      and power performances, which is possible related to the interference of
      concurrent training effects. New training strategies should be developed to
      ensure adequate balance between power and endurance loads throughout short (and
      high-volume) soccer preseasons.

PMID- 29018360
TI  - Adenosine: Direct and Indirect Actions on Gastric Acid Secretion.
AB  - Composed by a molecule of adenine and a molecule of ribose, adenosine is a
      paradigm of recyclable nucleoside with a multiplicity of functions that occupies
      a privileged position in the metabolic and regulatory contexts. Adenosine is
      formed continuously in intracellular and extracellular locations of all tissues.
      Extracellular adenosine is a signaling molecule, able to modulate a vast range of
      physiologic responses in many cells and organs, including digestive organs. The
      adenosine A1, A2A, A2B, and A3 receptors are P1 purinergic receptors, G protein
      coupled proteins implicated in tissue protection. This review is focused on
      gastric acid secretion, a process centered on the parietal cell of the stomach,
      which contains large amounts of H+/K+-ATPase, the proton pump responsible for
      proton extrusion during acid secretion. Gastric acid secretion is regulated by an
      extensive collection of neural stimuli and endocrine and paracrine agents, which
      act either directly at membrane receptors of the parietal cell or indirectly
      through other regulatory cells of the gastric mucosa, as well as mechanic and
      chemic stimuli. In this review, after briefly introducing these points, we
      condense the current body of knowledge about the modulating action of adenosine
      on the pathophysiology of gastric acid secretion and update its significance
      based on recent findings in gastric mucosa and parietal cells in humans and
      animal models.

PMID- 29018363
TI  - Moderate-Load Muscular Endurance Strength Training Did Not Improve Peak Power or
      Functional Capacity in Older Men and Women.
AB  - The present study determined the effects of muscular endurance strength training
      on maximum strength and power, functional capacity, muscle activation and
      hypertrophy in older men and women. Eighty-one men and women acted as an
      intervention group while 22 acted as non-training controls (age range 64-75 y).
      Intervention training included super-sets (i.e., paired exercises, immediately
      performing the second exercises following completion of the first) with short
      rest intervals (30-60 s between sets) at an intensity of 50-60% one-repetition
      maximum (1-RM) for 15-20 repetitions. Concentric leg press actions measured
      maximum strength (1-RM) and concentric peak power. Functional capacity was
      assessed by maximum speed walking tests (i.e., forward walk, backward walk, timed
      up-and-go, and stair climb tests). Quadriceps muscle activation was assessed by
      surface electromyogram and twitch interpolation technique. Vastus lateralis cross
      sectional area was measured by panoramic ultrasound. Compared to control, the
      intervention groups increased maximum strength (1-RM; men: 10 +/- 7% vs. 2 +/-
      3%, women: 14 +/- 9% vs. 1 +/- 6% both P < 0.01) and vastus lateralis cross
      sectional area (men: 6 +/- 7% vs. -3 +/- 6%, women: 10 +/- 10% vs. 0 +/- 4% both
      P < 0.05). But there were no between-group differences in peak power, muscle
      activation or functional capacity (e.g., stair climb; men: -5 +/- 7% vs. -4 +/-
      3%, women: -5 +/- 6% vs. -2 +/- 5% both P > 0.05). While benefits occurred during
      muscular endurance strength training, specific stimuli are probably needed to
      target all aspects of age-related health.

PMID- 29018364
TI  - Cloning and Functional Characterization of Octbeta2-Receptor and Tyr1-Receptor in
      the Chagas Disease Vector, Rhodnius prolixus.
AB  - Octopamine and tyramine, both biogenic amines, are bioactive chemicals important
      in diverse physiological processes in invertebrates. In insects, octopamine and
      tyramine operate analogously to epinephrine and norepinephrine in the
      vertebrates. Octopamine and tyramine bind to G-protein coupled receptors (GPCRs)
      leading to changes in second messenger levels and thereby modifying the function
      in target tissues and insect behavior. In this paper, we report the cDNA
      sequences of two GPCRs, RhoprOctbeta2-R, and RhoprTyr1-R, have been cloned and
      functionally characterized from Rhodnius prolixus. Octopamine and tyramine each
      activate RhoprOctbeta2-R and RhoprTyr1-R in a dose-dependent manner. Octopamine
      is one order of magnitude more potent than tyramine in activating RhoprOctbeta2
      R. Tyramine is two orders of magnitude more potent than octopamine in activating
      RhoprTyr1-R. Phentolamine and gramine significantly antagonize RhoprOctbeta2-R,
      whereas yohimbine and phenoxybenzamine are effective blockers of RhoprTyr1-R. The
      transcripts of both receptors are enriched in the central nervous system (CNS)
      and are expressed throughout the adult female reproductive system. It has been
      shown in other insects that Octbeta2-R is essential for processes such as
      ovulation and fertilization. We previously reported that octopamine and tyramine
      modulate oviducts and bursa contractions in R. prolixus. Our data confirm the
      importance of octopamine and tyramine signaling in the reproductive system of R.
      prolixus.

PMID- 29018365
TI  - Searching for the Haplorrhine Heterotherm: Field and Laboratory Data of Free
      Ranging Tarsiers.
AB  - The observation of heterothermy in a single suborder (Strepsirrhini) only within
      the primates is puzzling. Given that the placental-mammal ancestor was likely a
      heterotherm, we explored the potential for heterothermy in a primate closely
      related to the Strepsirrhini. Based upon phylogeny, body size and habitat
      stability since the Late Eocene, we selected western tarsiers (Cephalopachus
      bancanus) from the island of Borneo. Being the sister clade to Strepsirrhini and
      basal in Haplorrhini (monkeys and apes), we hypothesized that C. bancanus might
      have retained the heterothermic capacity observed in several small
      strepsirrhines. We measured resting metabolic rate, subcutaneous temperature,
      evaporative water loss and the percentage of heat dissipated through evaporation,
      at ambient temperatures between 22 and 35 degrees C in fresh-caught wild animals
      (126.1 +/- 2.4 g). We also measured core body temperatures in free-ranging
      animals. The thermoneutral zone was 25-30 degrees C and the basal metabolic rate
      was 3.52 +/- 0.06 W.kg-1 (0.65 +/- 0.01 ml O2.g-1.h-1). There was no evidence of
      adaptive heterothermy in either the laboratory data or the free-ranging data.
      Instead, animals appeared to be cold sensitive (Tb ~ 31 degrees C) at the lowest
      temperatures. We discuss possible reasons for the apparent lack of heterothermy
      in tarsiers, and identify putative heterotherms within Platyrrhini. We also
      document our concern for the vulnerability of C. bancanus to future temperature
      increases associated with global warming.

PMID- 29018366
TI  - Editorial: Cardiac Remodeling: New Insights in Physiological and Pathological
      Adaptations.

PMID- 29018370
TI  - Empathic and Self-Regulatory Processes Governing Doping Behavior.
AB  - Evidence associating doping behavior with moral disengagement (MD) has
      accumulated over recent years. However, to date, research examining links between
      MD and doping has not considered key theoretically grounded influences and
      outcomes of MD. As such, there is a need for quantitative research in relevant
      populations that purposefully examines the explanatory pathways through which MD
      is thought to operate. Toward this end, the current study examined a conceptually
      grounded model of doping behavior that incorporated empathy, doping self
      regulatory efficacy (SRE), doping MD, anticipated guilt and self-reported
      doping/doping susceptibility. Participants were specifically recruited to
      represent four key physical-activity contexts and consisted of team- (n = 195)
      and individual- (n = 169) sport athletes and hardcore- (n = 125) and corporate-
      (n = 121) gym exercisers representing both genders (nmale = 371; nfemale = 239);
      self-reported lifetime prevalence of doping across the sample was 13.6%. Each
      participant completed questionnaires assessing the aforementioned variables.
      Structural equation modeling indicated strong support for all study hypotheses.
      Specifically, we established: (a) empathy and doping SRE negatively predicted
      reported doping; (b) the predictive effects of empathy and doping SRE on reported
      doping were mediated by doping MD and anticipated guilt; (c) doping MD positively
      predicted reported doping; (d) the predictive effects of doping MD on reported
      doping were partially mediated by anticipated guilt. Substituting self-reported
      doping for doping susceptibility, multisample analyses then demonstrated these
      predictive effects were largely invariant between males and females and across
      the four physical-activity contexts represented. These findings extend current
      knowledge on a number of levels, and in doing so aid our understanding of key
      psychosocial processes that may govern doping behavior across key physical
      activity contexts.

PMID- 29018368
TI  - Biclustered Independent Component Analysis for Complex Biomarker and Subtype
      Identification from Structural Magnetic Resonance Images in Schizophrenia.
AB  - Clinical and cognitive symptoms domain-based subtyping in schizophrenia (Sz) has
      been critiqued due to the lack of neurobiological correlates and heterogeneity in
      symptom scores. We, therefore, present a novel data-driven framework using
      biclustered independent component analysis to detect subtypes from the reliable
      and stable gray matter concentration (GMC) of patients with Sz. The developed
      methodology consists of the following steps: source-based morphometry (SBM)
      decomposition, selection and sorting of two component loadings, subtype component
      reconstruction using group information-guided ICA (GIG-ICA). This framework was
      applied to the top two group discriminative components namely the insula/superior
      temporal gyrus/inferior frontal gyrus (I-STG-IFG component) and the superior
      frontal gyrus/middle frontal gyrus/medial frontal gyrus (SFG-MiFG-MFG component)
      from our previous SBM study, which showed diagnostic group difference and had the
      highest effect sizes. The aggregated multisite dataset consisted of 382 patients
      with Sz regressed of age, gender, and site voxelwise. We observed two subtypes
      (i.e., two different subsets of subjects) each heavily weighted on these two
      components, respectively. These subsets of subjects were characterized by
      significant differences in positive and negative syndrome scale (PANSS) positive
      clinical symptoms (p = 0.005). We also observed an overlapping subtype weighing
      heavily on both of these components. The PANSS general clinical symptom of this
      subtype was trend level correlated with the loading coefficients of the SFG-MiFG
      MFG component (r = 0.25; p = 0.07). The reconstructed subtype-specific component
      using GIG-ICA showed variations in voxel regions, when compared to the group
      component. We observed deviations from mean GMC along with conjunction of
      features from two components characterizing each deciphered subtype. These
      inherent variations in GMC among patients with Sz could possibly indicate the
      need for personalized treatment and targeted drug development.

PMID- 29018369
TI  - A Solution to Modeling Multilevel Confirmatory Factor Analysis with Data Obtained
      from Complex Survey Sampling to Avoid Conflated Parameter Estimates.
AB  - The issue of equality in the between-and within-level structures in Multilevel
      Confirmatory Factor Analysis (MCFA) models has been influential for obtaining
      unbiased parameter estimates and statistical inferences. A commonly seen
      condition is the inequality of factor loadings under equal level-varying
      structures. With mathematical investigation and Monte Carlo simulation, this
      study compared the robustness of five statistical models including two model
      based (a true and a mis-specified models), one design-based, and two maximum
      models (two models where the full rank of variance-covariance matrix is estimated
      in between level and within level, respectively) in analyzing complex survey
      measurement data with level-varying factor loadings. The empirical data of 120
      3rd graders' (from 40 classrooms) perceived Harter competence scale were modeled
      using MCFA and the parameter estimates were used as true parameters to perform
      the Monte Carlo simulation study. Results showed maximum models was robust to
      unequal factor loadings while the design-based and the miss-specified model-based
      approaches produced conflated results and spurious statistical inferences. We
      recommend the use of maximum models if researchers have limited information about
      the pattern of factor loadings and measurement structures. Measurement models are
      key components of Structural Equation Modeling (SEM); therefore, the findings can
      be generalized to multilevel SEM and CFA models. Mplus codes are provided for
      maximum models and other analytical models.

PMID- 29018371
TI  - What Vowels Can Tell Us about the Evolution of Music.
AB  - Whether music and language evolved independently of each other or whether both
      evolved from a common precursor remains a hotly debated topic. We here emphasize
      the role of vowels in the language-music relationship, arguing for a shared
      heritage of music and speech. Vowels play a decisive role in generating the sound
      or sonority of syllables, the main vehicles for transporting prosodic information
      in speech and singing. Timbre is, beyond question, the primary parameter that
      allows us to discriminate between different vowels, but vowels also have
      intrinsic pitch, intensity, and duration. There are striking correspondences
      between the number of vowels and the number of pitches in musical scales across
      cultures: an upper limit of roughly 12 elements, a lower limit of 2, and a
      frequency peak at 5-7 elements. Moreover, there is evidence for correspondences
      between vowels and scales even in specific cultures, e.g., cultures with three
      vowels tend to have tritonic scales. We report a match between vowel pitch and
      musical pitch in meaningless syllables of Alpine yodelers, and highlight the
      relevance of vocal timbre in the music of many non-Western cultures, in which
      vocal timbre/vowel timbre and musical melody are often intertwined. Studies
      showing the pivotal role of vowels and their musical qualities in the ontogeny of
      language and in infant directed speech, will be used as further arguments
      supporting the hypothesis that music and speech evolved from a common prosodic
      precursor, where the vowels exhibited both pitch and timbre variations.

PMID- 29018367
TI  - Treatment of Comorbid Alcohol Dependence and Anxiety Disorder: Review of the
      Scientific Evidence and Recommendations for Treatment.
AB  - Patients with alcohol-use disorders (AUDs) have a high prevalence of anxiety
      disorders (AnxDs). "Co-occurring disorders" refers to the coexistence of an AUD
      and/or drug related disorders with another non-addictive psychiatric disorder.
      The aim of this study was to assess the effectiveness of psychopharmacological
      treatments and psychotherapy in patients with AUD and AnxD and to propose
      recommendations for the treatment of patients with comorbid AnxDs and AUDs.
      Randomized clinical trials, meta-analyses, and clinical guidelines were retrieved
      from PubMed, Embase, and Cochrane databases. Paroxetine was found to be effective
      in social anxiety patients with alcohol dependence. Selective serotonin reuptake
      inhibitors (SSRIs), especially sertraline, showed effective results in
      posttraumatic stress disorder and in comorbid AnxD-AUD. However, SSRIs should be
      used with caution when patients are actively drinking because they may increase
      alcohol consumption. Buspirone, gabapentin, and pregabalin were found to be
      effective in comorbid AnxD-AUD. The treatment of dual AnxDs should start as early
      as possible. Since AUDs and AnxDs can reinforce each other, treatments targeting
      both pathologies can be effective. Women suffer from higher levels of stress and
      AnxDs than men, and they are also more vulnerable to maintaining alcohol
      consumption levels. Further research is needed in this comorbid patient
      population, including the study of different types of patients and gender
      perspectives.

PMID- 29018372
TI  - Neurodiversity, Giftedness, and Aesthetic Perceptual Judgment of Music in
      Children with Autism.
AB  - The author investigated the capability of aesthetic perceptual judgment of music
      in male children diagnosed with autism spectrum disorder (ASD) when compared to
      age-matched typically developing (TD) male children. Nineteen boys between 4 and
      7 years of age with ASD were compared to 28 TD boys while listening to musical
      stimuli of different aesthetic levels. The results from two musical experiments
      using the above participants, are described here. In the first study, responses
      to a Mozart minuet and a dissonant altered version of the same Mozart minuet were
      compared. In this first study, the results indicated that both ASD and TD males
      preferred listening to the original consonant version of the minuet over the
      altered dissonant version. With the same participants, the second experiment
      included musical stimuli from four renowned composers: Mozart and Bach's musical
      works, both considered consonant in their harmonic structure, were compared with
      music from Schoenberg and Albinoni, two composers who wrote musical works
      considered exceedingly harmonically dissonant. In the second study, when the
      stimuli included consonant or dissonant musical stimuli from different composers,
      the children with ASD showed greater preference for the aesthetic quality of the
      highly dissonant music compared to the TD children. While children in both of the
      groups listened to the consonant stimuli of Mozart and Bach music for the same
      amount of time, the children with ASD listened to the dissonant music of
      Schoenberg and Albinoni longer than the TD children. As preferring dissonant
      music is more aesthetically demanding perceptually, these results suggest that
      ASD male children demonstrate an enhanced capability of aesthetic judgment of
      music. Subsidiary data collected after the completion of the experiment revealed
      that absolute pitch ability was prevalent only in the children with ASD, some of
      whom also possessed extraordinary musical memory. The implications of these
      results are discussed with reference to the broader notion of neurodiversity, a
      term coined to capture potentially gifted qualities in individuals diagnosed with
      ASD.

PMID- 29018373
TI  - Behavioral Oscillations in Visual Attention Modulated by Task Difficulty.
AB  - The spotlight of attention is full of discrete moments and operates periodically.
      Recently, it has been well-documented there were behavioral oscillations in
      visual attention, however, different periodicities were demonstrated. Task
      difficulty may be an important factor causing disagreement in attentional
      periodic patterns. The present study examined behavioral oscillations in visual
      attention during difficult and easy tasks. A modified high temporal resolution
      cue-target paradigm in which the cue-target stimulus onset asynchrony (SOAs)
      varied from 0.1 to 1.08 s in steps of 20 ms was used. The target was detected
      with the accuracy of 65% in the difficult condition and 75% in the easy
      condition. Oscillatory patterns were analyzed and observed in behavioral
      performance. A theta rhythm was visible in the difficult version. However,
      attention oscillation increased to a higher frequency in the easy version. Task
      difficulty was negatively related to power for all bands. Our findings suggest
      that the attention spotlight switched faster when the task was easy, while, it
      switched much more slowly when the task was difficult in order to obtain more
      information. A flexible mechanism for attention spotlight was demonstrated, and
      task demand modulated attention oscillations.

PMID- 29018374
TI  - Psychological Health in the Retirement Transition: Rationale and First Findings
      in the HEalth, Ageing and Retirement Transitions in Sweden (HEARTS) Study.
AB  - From an aging research and life-course perspective, the transition to retirement
      marks a significant life-event and provides a unique opportunity to study
      psychological health and coping during a period of substantial change in everyday
      life. The aim of the present paper is to: (a) outline the rationale of the
      HEalth, Ageing and Retirement Transitions in Sweden (HEARTS) study, (b) describe
      the study sample, and (c) to present some initial results from the two first
      waves regarding the association between retirement status and psychological
      health. The HEARTS study is designed to annually study psychological health in
      the years before and following retirement, and to examine change and stability
      patterns related to the retirement event. Among a representative Swedish
      population-based sample of 14,990 individuals aged 60-66 years, 5,913 completed
      the baseline questionnaire in 2015. The majority of the participants (69%)
      completed a web-based survey, and the rest (31%) completed a paper version. The
      baseline HEARTS sample represents the general population well in terms of gender
      and age, but is more highly educated. Cross-sectional findings from the first
      wave showed that retired individuals demonstrated better psychological health
      compared to those who were still working. Longitudinal results from the first and
      second waves showed that individuals who retired between waves showed more
      positive changes in psychological health compared with those still working or
      previously retired.

PMID- 29018375
TI  - One Label or Two? Linguistic Influences on the Similarity Judgment of Objects
      between English and Japanese Speakers.
AB  - Recent findings have re-examined the linguistic influence on cognition and
      perception, while identifying evidence that supports the Whorfian hypothesis. We
      examine how English and Japanese speakers perceive similarity of pairs of
      objects, by using two sets of stimuli: one in which two distinct linguistic
      categories apply to respective object images in English, but only one linguistic
      category applies in Japanese; and another in which two distinct linguistic
      categories apply to respective object images in Japanese, but only one applies in
      English. We conducted four studies and tested different groups of participants in
      each of them. In Study 1, we asked participants to name the two objects before
      engaging in the similarity judgment task. Here, we expected a strong linguistic
      effect. In Study 2, we asked participants to engage in the same task without
      naming, where we assumed that the condition is close enough to our daily visual
      information processing where language is not necessarily prompted. We further
      explored whether the language still influences the similarity perception by
      asking participants to engage in the same task basing on the visual similarity
      (Study 3) and the functional similarity (Study 4). The results overall indicated
      that English and Japanese speakers perceived the two objects to be more similar
      when they were in the same linguistic categories than when they were in different
      linguistic categories in their respective languages. Implications for research
      testing the Whorfian hypothesis and the requirement for methodological
      development beyond behavioral measures are discussed.

PMID- 29018376
TI  - Future Time Perspective in Occupational Teams: Do Older Workers Prefer More
      Familiar Teams?
AB  - Working in teams is quite popular across different industries and cultures. While
      some of these teams exist for longer time periods, other teams collaborate only
      for short periods and members switch into new teams after goals are accomplished.
      However, workers' preferences for joining a new team might vary in different
      ways. Based on Carstensen's socioemotional selectivity theory, we predict that
      emotionally meaningful teams are prioritized when occupational future time
      perspective (OFTP) is perceived as limited. Building and expanding on studies
      outside of the work context, we expected that older as compared to younger
      workers prefer more familiar teams, and that this effect is mediated by workers'
      OFTP. Moreover, we assumed that experimentally manipulated OFTP can change such
      team preferences. The hypotheses were tested in an online scenario study using
      three experimental conditions (within-person design). Four hundred and fifty-four
      workers (57% female, age M = 45.98, SD = 11.46) were asked to choose between a
      familiar and a new team in three consecutive trials: under an unspecified OFTP
      (baseline), under an expanded OFTP (amendment of retirement age), and under a
      restricted OFTP (insolvency of the current company). Whereas the baseline
      condition was always first, the order of the second and third conditions was
      randomized among participants. In the baseline condition, results showed the
      expected mediation effect of workers' OFTP on the relation between workers' age
      and preference for a familiar over a new team. Higher age was associated with
      more limited OFTP, which in turn was associated with higher preference for a
      familiar over a new team. Moreover, experimentally restricting OFTP increased
      preference for a familiar team over a new team regardless of workers' age,
      providing further evidence for the assumed causal processes and showing
      interesting avenues for practical interventions in occupational teams.

PMID- 29018377
TI  - Perceptual Sensitivity and Response to Strong Stimuli Are Related.
AB  - To shed new light on the long-standing debate about the (in)dependence of
      sensitivity to weak stimuli and overreactivity to strong stimuli, we examined the
      relation between these tendencies within the neurobehavioral framework of the
      Predictive and Reactive Control Systems (PARCS) theory (Tops et al., 2010, 2014).
      Whereas previous studies only considered overreactivity in terms of the
      individual tendency to experience unpleasant affect (punishment reactivity)
      resulting from strong sensory stimulation, we also took the individual tendency
      to experience pleasant affect (reward reactivity) resulting from strong sensory
      stimulation into account. According to PARCS theory, these temperamental
      tendencies overlap in terms of high reactivity toward stimulation, but oppose
      each other in terms of the response orientation (approach or avoid). PARCS theory
      predicts that both types of reactivity to strong stimuli relate to sensitivity to
      weak stimuli, but that these relationships are suppressed due to the opposing
      relationship between reward and punishment reactivity. We measured punishment and
      reward reactivity to strong stimuli and sensitivity to weak stimuli using scales
      from the Adult Temperament Questionnaire (Evans and Rothbart, 2007). Sensitivity
      was also measured more objectively using the masked auditory threshold. We found
      that sensitivity to weak stimuli (both self-reported and objectively assessed)
      was positively associated with self-reported punishment and reward reactivity to
      strong stimuli, but only when these reactivity measures were controlled for each
      other, implicating a mutual suppression effect. These results are in line with
      PARCS theory and suggest that sensitivity to weak stimuli and overreactivity are
      dependent, but this dependency is likely to be obscured if punishment and reward
      reactivity are not both taken into account.

PMID- 29018379
TI  - Word Order and Voice Influence the Timing of Verb Planning in German Sentence
      Production.
AB  - Theories of incremental sentence production make different assumptions about when
      speakers encode information about described events and when verbs are selected,
      accordingly. An eye tracking experiment on German testing the predictions from
      linear and hierarchical incrementality about the timing of event encoding and
      verb planning is reported. In the experiment, participants described depictions
      of two-participant events with sentences that differed in voice and word order.
      Verb-medial active sentences and actives and passives with sentence-final verbs
      were compared. Linear incrementality predicts that sentences with verbs placed
      early differ from verb-final sentences because verbs are assumed to only be
      planned shortly before they are articulated. By contrast, hierarchical
      incrementality assumes that speakers start planning with relational encoding of
      the event. A weak version of hierarchical incrementality assumes that only the
      action is encoded at the outset of formulation and selection of lexical verbs
      only occurs shortly before they are articulated, leading to the prediction of
      different fixation patterns for verb-medial and verb-final sentences. A strong
      version of hierarchical incrementality predicts no differences between verb
      medial and verb-final sentences because it assumes that verbs are always
      lexically selected early in the formulation process. Based on growth curve
      analyses of fixations to agent and patient characters in the described pictures,
      and the influence of character humanness and the lack of an influence of the
      visual salience of characters on speakers' choice of active or passive voice, the
      current results suggest that while verb planning does not necessarily occur early
      during formulation, speakers of German always create an event representation
      early.

PMID- 29018378
TI  - Contextualized Contribution of Kindness to Favorable Goal- and Circumstantial
      Driven Neuropsychological Regulation.
AB  - Kindness involves care and non-judgmental understanding toward someone. As a
      prosocial inclination, kindness would increase the possibility of favorable
      interaction with the environment, with a successful adjustment of one's response
      in novel or challenging circumstances, taking into account rules or goals. This
      adjustment ability is commonly referred to as executive functions, dependent on
      the prefrontal and parietal functioning, still under development during late
      adolescence. This study aimed to investigate if kindness would relate with the
      executive functions. If so, it would correlate more with measures of self
      regulation, mainly dependent on the medial prefrontal corticosubcortical
      circuits. Also, among self-regulating processes, kindness would be more
      associated with autonomic responses-choices guided by one's
      understanding/intention - than with adaptive responses-changes on one's choices
      triggered by unfavorable circumstances. A sample of 46 (31 female; 18 to 21 years
      old) healthy college students from the University of the State of Rio de Janeiro
      attended a clinical interview and a comprehensive neuropsychological assessment.
      Kindness was measured by the Compassion Scale subscore. Generalized non-linear
      models for each neuropsychological variable were executed on R, followed by an
      estimation of weighted parameters for each factor. Significant models which
      included kindness (weighted parameter Pc > 74) and all of their psychosocial or
      sociodemographic factors on their maximum expression (Pc > 74) were identified.
      In a contextualized joint influence with other psychosocial and sociodemographic
      factors, kindness fits equally goal- and circumstantial- self-regulation, as well
      as integrative organization of information. Kindness is a principle that
      optimizes a refreshing and prosocial interaction with the environment. As it
      anticipates sharing and cooperation behaviors, it might have a primordial
      function on individual and social development.

PMID- 29018380
TI  - College Binge Drinking Associated with Decreased Frontal Activation to Negative
      Emotional Distractors during Inhibitory Control.
AB  - The transition to college is associated with an increase in heavy episodic
      alcohol use, or binge drinking, during a time when the prefrontal cortex and
      prefrontal-limbic circuitry continue to mature. Traits associated with this
      immaturity, including impulsivity in emotional contexts, may contribute to risky
      and heavy episodic alcohol consumption. The current study used blood oxygen level
      dependent (BOLD) multiband functional magnetic resonance imaging (fMRI) to assess
      brain activation during a task that required participants to ignore background
      images with positive, negative, or neutral emotional valence while performing an
      inhibitory control task (Go-NoGo). Subjects were 23 college freshmen (seven male,
      18-20 years) who engaged in a range of drinking behavior (past 3 months' binge
      episodes range = 0-19, mean = 4.6, total drinks consumed range = 0-104, mean =
      32.0). Brain activation on inhibitory trials (NoGo) was contrasted between
      negative and neutral conditions and between positive and neutral conditions using
      non-parametric testing (5000 permutations) and cluster-based thresholding (z =
      2.3), p <= 0.05 corrected. Results showed that a higher recent incidence of binge
      drinking was significantly associated with decreased activation of dorsolateral
      prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and anterior
      cingulate cortex (ACC), brain regions strongly implicated in executive
      functioning, during negative relative to neutral inhibitory trials. No
      significant associations between binge drinking and brain activation were
      observed for positive relative to neutral images. While task performance was not
      significantly associated with binge drinking in this sample, subjects with
      heavier recent binge drinking showed decreased recruitment of executive control
      regions under negative versus neutral distractor conditions. These findings
      suggest that in young adults with heavier recent binge drinking, processing of
      negative emotional images interferes more with inhibitory control neurocircuitry
      than in young adults who do not binge drink often. This pattern of altered
      frontal lobe activation associated with binge drinking may serve as an early
      marker of risk for future self-regulation deficits that could lead to problematic
      alcohol use. These findings underscore the importance of understanding the impact
      of emotion on cognitive control and associated brain functioning in binge
      drinking behaviors among young adults.

PMID- 29018382
TI  - How Native Prosody Affects Pitch Processing during Word Learning in Limburgian
      and Dutch Toddlers and Adults.
AB  - In this study, Limburgian and Dutch 2.5- to 4-year-olds and adults took part in a
      word learning experiment. Following the procedure employed by Quam and Swingley
      (2010) and Singh et al. (2014), participants learned two novel word-object
      mappings. After training, word recognition was tested in correct pronunciation
      (CP) trials and mispronunciation (MP) trials featuring a pitch change. Since
      Limburgian is considered a restricted tone language, we expected that the pitch
      change would hinder word recognition in Limburgian, but not in non-tonal Dutch
      listeners. Contrary to our expectations, both Limburgian and Dutch children
      appeared to be sensitive to pitch changes in newly learned words, indicated by a
      significant decrease in target fixation in MP trials compared to CP trials.
      Limburgian and Dutch adults showed very strong naming effects in both trial
      types. The results are discussed against the background of the influence of the
      native prosodic system.

PMID- 29018383
TI  - Study Protocol for the Preschooler Regulation of Emotional Stress (PRES)
      Procedure.
AB  - Background: Emotional stress regulation (ESR) rapidly develops during the first
      months of age and includes different behavioral strategies which largely
      contribute to children's behavioral and emotional adjustment later in life. The
      assessment of ESR during the first years of life is critical to identify
      preschool children who are at developmental risk. Although ESR is generally
      included in larger temperament batteries [e.g., the Laboratory Temperament
      Assessment Battery (Lab-TAB)], there is no standardized observational procedure
      to specifically assess and measure ESR in preschool aged children. Aim: Here, we
      describe the development of an observational procedure to assess ESR in preschool
      aged children [i.e., the Preschooler Regulation of Emotional Stress (PRES)
      Procedure] and the related coding system. Methods: Four Lab-TAB emotional stress
      episodes (i.e., the Stranger, the Perfect Circle, the Missing Sticker, and the
      Transparent Box) have been selected. Independent coders developed a list of ESR
      codes resulting in two general indexes (i.e., active engagement and stress level)
      and five specific indexes (i.e., anger, control, fear, inhibition, sadness).
      Finally, specific actions have been planned to assess the validity and the coding
      system reliability of PRES procedure. Ethics and Dissemination: The study has
      been approved by the Ethical Committee of the Scientific Institute IRCCS Eugenio
      Medea, Bosisio Parini (Italy). The PRES validation and reliability assessment as
      well as its use with healthy and at-risk populations of preschool children will
      be object of future scientific publications and international conference
      presentations.

PMID- 29018385
TI  - Editorial: Theoretical Issues on Sensory Perception-Approaches from Philosophy,
      Psychology, and Neuroscience.

PMID- 29018386
TI  - Beyond Likeability: Investigating Social Interactions with Artificial Agents and
      Objective Metrics.

PMID- 29018384
TI  - Attentional Control and Fear Extinction in Subclinical Fear: An Exploratory
      Study.
AB  - Attentional control (AC) and fear extinction learning are known to be involved in
      pathological anxiety. In this study we explored whether individual differences in
      non-emotional AC were associated with individual differences in the magnitude and
      gradient of fear extinction (learning and recall). In 50 individuals with fear of
      spiders, we collected measures of non-emotional AC by means of self-report and by
      assessing the functioning of the major attention networks (executive control,
      orienting, and alerting). The participants then underwent a paradigm assessing
      fear extinction learning and extinction recall. The two components of the
      orienting network functioning (costs and benefits) were significantly associated
      with fear extinction gradient over and above the effects of trait anxiety.
      Specifically, participants with enhanced orienting costs (i.e., difficulties in
      disengaging attention from cues not relevant for the task) showed faster
      extinction learning, while those with enhanced orienting benefits (i.e.,
      attention facilitated by valid cues) exhibited faster extinction recall as
      measured by fear-potentiated startle and Unconditioned Stimulus expectancies,
      respectively. Our findings suggest that, in non-emotional conditions, the
      orienting component of attention may be predictive of fear extinction. They also
      show that the use of fear extinction gradients and the exploration of individual
      differences in non-emotional AC (using performance-based measures of attentional
      network functioning) can provide a better understanding of individual differences
      in fear learning. Our findings also may help to understand differences in
      exposure therapy outcomes.

PMID- 29018387
TI  - The Role of Attention Shifting in Orthographic Competencies: Cross-Sectional
      Findings from 1st, 3rd, and 8th Grade Students.
AB  - Attention shifting refers to one core component of executive functions, a set of
      higher-order cognitive processes that predict different aspects of academic
      achievement. To date, few studies have investigated the role of attention
      shifting in orthographic competencies during middle childhood and early
      adolescence. In the present study, 69 first-grade, 121 third-grade, and 85 eighth
      grade students' attention shifting was tested with a computer version of the
      Dimensional Change Card Sort (DCCS; Zelazo, 2006). General spelling skills and
      specific writing and spelling strategies were assessed with the Hamburger Writing
      Test (May, 2002). Results suggested associations between attention shifting and
      various orthographic competencies that differ across age groups and by sex.
      Across all age groups, better attention shifting was associated with less errors
      in applying alphabetical strategies. In third graders, better attention shifting
      was furthermore related to better general spelling skills and less errors in
      using orthographical strategies. In this age group, associations did not differ
      by sex. Among first graders, attention shifting was negatively related to general
      spelling skills, but only for boys. In contrast, attention shifting was
      positively related to general spelling skills in eighth graders, but only for
      girls. Finally, better attention shifting was associated with less case-related
      errors in eighth graders, independent of students' sex. In sum, the data provide
      insight into both variability and consistency in the pattern of relations between
      attention shifting and various orthographic competencies among elementary and
      middle school students.

PMID- 29018381
TI  - The Role of Working Memory for Cognitive Control in Anorexia Nervosa versus
      Substance Use Disorder.
AB  - Prefrontal cortex executive functions, such as working memory (WM) interact with
      limbic processes to foster impulse control. Such an interaction is referred to in
      a growing body of publications by terms such as cognitive control, cognitive
      inhibition, affect regulation, self-regulation, top-down control, and cognitive
      emotion interaction. The rising trend of research into cognitive control of
      impulsivity, using various related terms reflects the importance of research into
      impulse control, as failure to employ cognitions optimally may eventually result
      in mental disorder. Against this background, we take a novel approach using an
      impulse control spectrum model - where anorexia nervosa (AN) and substance use
      disorder (SUD) are at opposite extremes - to examine the role of WM for cognitive
      control. With this aim, we first summarize WM processes in the healthy brain in
      order to frame a systematic review of the neuropsychological, neural and genetic
      findings of AN and SUD. In our systematic review of WM/cognitive control, we
      found n = 15 studies of AN with a total of n = 582 AN and n = 365 HC
      participants; and n = 93 studies of SUD with n = 9106 SUD and n = 3028 HC
      participants. In particular, we consider how WM load/capacity may support the
      neural process of excessive epistemic foraging (cognitive sampling of the
      environment to test predictions about the world) in AN that reduces distraction
      from salient stimuli. We also consider the link between WM and cognitive control
      in people with SUD who are prone to 'jumping to conclusions' and reduced
      epistemic foraging. Finally, in light of our review, we consider WM training as a
      novel research tool and an adjunct to enhance treatment that improves cognitive
      control of impulsivity.

PMID- 29018388
TI  - EMDR beyond PTSD: A Systematic Literature Review.
AB  - Background: Eye Movement Desensitization and Reprocessing (EMDR) is a
      psychotherapeutic approach that has demonstrated efficacy in the treatment of
      Post-traumatic Stress Disorder (PTSD) through several randomized controlled
      trials (RCT). Solid evidence shows that traumatic events can contribute to the
      onset of severe mental disorders and can worsen their prognosis. The aim of this
      systematic review is to summarize the most important findings from RCT conducted
      in the treatment of comorbid traumatic events in psychosis, bipolar disorder,
      unipolar depression, anxiety disorders, substance use disorders, and chronic back
      pain. Methods: Using PubMed, ScienceDirect, and Scopus, we conducted a systematic
      literature search of RCT studies published up to December 2016 that used EMDR
      therapy in the mentioned psychiatric conditions. Results: RCT are still scarce in
      these comorbid conditions but the available evidence suggests that EMDR therapy
      improves trauma-associated symptoms and has a minor effect on the primary
      disorders by reaching partial symptomatic improvement. Conclusions: EMDR therapy
      could be a useful psychotherapy to treat trauma-associated symptoms in patients
      with comorbid psychiatric disorders. Preliminary evidence also suggests that EMDR
      therapy might be useful to improve psychotic or affective symptoms and could be
      an add-on treatment in chronic pain conditions.

PMID- 29018389
TI  - Measuring Depression in a Non-Western War-Affected Displaced Population:
      Measurement Equivalence of the Beck Depression Inventory.
AB  - Depression is commonly seen in survivors of conflict and disaster across the
      world. There is a dearth of research on the validity of commonly used measures of
      depression in these populations. Measurements of depression that are used in
      multiple contexts need to meet measurement equivalence, i.e., the instrument
      measures the same construct in the same manner across different groups. The Beck
      Depression Inventory (BDI) was administered to female trauma survivors in the
      United States (n = 268) and female survivors of war in Sri Lanka (n = 149). Three
      metrics of measurement equivalence-structural, metric, and scalar-were examined.
      Two- and three-factor structures of the BDI that have been identified in other
      populations did not provide a good fit for our data. However, a bifactor model
      revealed a similar general distress dimension across populations, but dissimilar
      secondary dimensions or subfactors. The Sri Lankan subfactor comprised of
      predominantly somatic symptoms and the United States subfactor comprised of
      cognitive and somatic symptoms. While intercepts of individual BDI items
      differed, their differences seem to be offsetting. Total BDI scores across these
      two populations are roughly comparable, although caution is recommended when
      interpreting them. Making comparisons on subscales is not recommended.

PMID- 29018390
TI  - Ego Depletion in Real-Time: An Examination of the Sequential-Task Paradigm.
AB  - Current research into self-control that is based on the sequential task
      methodology is currently at an impasse. The sequential task methodology involves
      completing a task that is designed to tax self-control resources which in turn
      has carry-over effects on a second, unrelated task. The current impasse is in
      large part due to the lack of empirical research that tests explicit assumptions
      regarding the initial task. Five studies test one key, untested assumption
      underpinning strength (finite resource) models of self-regulation: Performance
      will decline over time on a task that depletes self-regulatory resources. In the
      aftermath of high profile replication failures using a popular letter-crossing
      task and subsequent criticisms of that task, the current studies examined whether
      depletion effects would occur in real time using letter-crossing tasks that did
      not invoke habit-forming and breaking, and whether these effects were moderated
      by administration type (paper and pencil vs. computer administration). Sample
      makeup and sizes as well as response formats were also varied across the studies.
      The five studies yielded a clear and consistent pattern of increasing performance
      deficits (errors) as a function of time spent on task with generally large
      effects and in the fifth study the strength of negative transfer effects to a
      working memory task were related to individual differences in depletion. These
      results demonstrate that some form of depletion is occurring on letter-crossing
      tasks though whether an internal regulatory resource reservoir or some other
      factor is changing across time remains an important question for future research.

PMID- 29018392
TI  - Using Procedure Based on Item Response Theory to Evaluate Classification
      Consistency Indices in the Practice of Large-Scale Assessment.
AB  - In spite of the growing interest in the methods of evaluating the classification
      consistency (CC) indices, only few researches are available in the field of
      applying these methods in the practice of large-scale educational assessment. In
      addition, only few studies considered the influence of practical factors, for
      example, the examinee ability distribution, the cut score location and the score
      scale, on the performance of CC indices. Using the newly developed Lee's
      procedure based on the item response theory (IRT), the main purpose of this study
      is to investigate the performance of CC indices when practical factors are taken
      into consideration. A simulation study and an empirical study were conducted
      under comprehensive conditions. Results suggested that with negatively skewed
      distribution, the CC indices were larger than with other distributions.
      Interactions occurred among ability distribution, cut score location, and score
      scale. Consequently, Lee's IRT procedure is reliable to be used in the field of
      large-scale educational assessment, and when reporting the indices, it should be
      treated with caution as testing conditions may vary a lot.

PMID- 29018391
TI  - The Presentation Location of the Reference Stimuli Affects the Left-Side Bias in
      the Processing of Faces and Chinese Characters.
AB  - For faces and Chinese characters, a left-side processing bias, in which observers
      rely more heavily on information conveyed by the left side of stimuli than the
      right side of stimuli, has been frequently reported in previous studies. However,
      it remains unclear whether this left-side bias effect is modulated by the
      reference stimuli's location. The present study adopted the chimeric stimuli task
      to investigate the influence of the presentation location of the reference
      stimuli on the left-side bias in face and Chinese character processing. The
      results demonstrated that when a reference face was presented in the left visual
      field of its chimeric images, which are centrally presented, the participants
      showed a preference higher than the no-bias threshold for the left chimeric face;
      this effect, however, was not observed in the right visual field. This finding
      indicates that the left-side bias effect in face processing is stronger when the
      reference face is in the left visual field. In contrast, the left-side bias was
      observed in Chinese character processing when the reference Chinese character was
      presented in either the left or right visual field. Together, these findings
      suggest that although faces and Chinese characters both have a left-side
      processing bias, the underlying neural mechanisms of this left-side bias might be
      different.

PMID- 29018393
TI  - Intergenerational Transmission of Resilience? Sense of Coherence Is Associated
      between Lithuanian Survivors of Political Violence and Their Adult Offspring.
AB  - Little is known about intergeneration effects on mental health in the families of
      survivors of political oppression of communist regime in Central and Eastern
      Europe. We aimed to explore post-traumatic stress in the second generation of the
      Lithuanian survivors of political violence, and analyze links between parental
      and adult offsprings' sense of coherence in the families exposed to political
      violence during the oppressive communist regime in Lithuania. A total of 110
      matched pairs of communist regime political violence survivors (mean age = 73.22
      years) and their adult offspring (mean age = 44.65 years) participated in this
      study. Life-time traumatic experiences and sense of coherence were measured in
      both parents and their offspring. Post-traumatic stress symptoms were assessed in
      the second generation of survivors. We found a high vulnerability in the second
      generation of the Lithuanian families of political violence survivors, with a 29%
      of probable PTSD in the second generation based on self-report measures. A
      significant positive correlation between parental and adult offsprings' sense of
      coherence was found. Post-traumatic stress symptoms were associated negatively
      with a sense of coherence in the second generation. Our study indicates the links
      between parental and the second generation's sense of coherence in the families
      of survivors of political violence. The study raises broader questions about the
      intergenerational aspects of resilience. Further studies are needed to explore
      the links between parental and child sense of coherence in other samples.

PMID- 29018394
TI  - Distress Levels among Parents of Active Duty Soldiers during Wartime.
AB  - Objective: Military service is a highly stressful period both for the soldiers
      serving and for their parents. Surprisingly, parents' experience has been mostly
      ignored in the research. This study's goal is to shed light on the experience and
      distress levels of parents of active duty combat soldiers during Operation
      Protective Edge, a military operation carried out by the Israel Defense Forces
      during July and August of 2014. Methods: During the advanced stages of the
      operation, 69 parents of Israeli male combat soldiers (55 mothers and 14 fathers)
      completed an online survey measuring symptoms of Posttraumatic Stress Disorder
      (PTSD-Checklist-5) and distress (Brief Symptom Inventory-18). Participants were
      recruited using a convenience sample, by posting ads on the public Facebook pages
      of the researchers and of the groups dedicated to parents of Israeli soldiers.
      Results: Parents' depression and anxiety symptom levels were higher than
      depression and anxiety symptom levels of the adult community norms in Israel.
      General distress rates of parents were similar to those presented by adults in
      southern Israel who were exposed for 7 years to the ongoing threat of daily
      rocket fire from Gaza, and higher than rates of a non-threatened Israeli
      population. Finally, 20.2% of the parents presented PTSD-like symptoms, a higher
      percentage than the probable PTSD diagnosis rates that were found in the general
      population in Israel during previous terror waves. Conclusion: This study
      provides preliminary evidence of soldiers' parents' distress and indicates the
      need for a better understanding of the impact of military service on soldiers'
      parents.

PMID- 29018395
TI  - Emotional Reactions Mediate the Effect of Music Listening on Creative Thinking:
      Perspective of the Arousal-and-Mood Hypothesis.
AB  - This study examined the effect of music listening on creative thinking through
      the lens of the arousal-and-mood hypothesis, which posits that emotional
      reactions (i.e., arousal and valence) mediate the effect of music listening on
      cognitive functioning. Participants were randomly assigned to three groups: a
      positive music group (n = 198), a negative music group (n = 195), and a control
      group (n = 191). Creative thinking and emotional reactions were assessed with the
      Test for Creative Thinking-Drawing Production and the Affect Grid, respectively.
      The results showed that both positively and negatively arousing music enhanced
      creative thinking. The results further revealed that arousal, regardless of
      valence, significantly mediated the music-creativity relationship. This study
      enriches the research on the arousal-and-mood hypothesis by (1) providing direct
      empirical testing on the mediating roles of emotional reactions; (2) including
      both positively and negatively arousing music in the study design; and (3)
      identifying that only arousal, and not valence, was a significant mediator in the
      music-creativity link.

PMID- 29018396
TI  - The Influence of Closeness Centrality on Lexical Processing.
AB  - The present study examined how the network science measure known as closeness
      centrality (which measures the average distance between a node and all other
      nodes in the network) influences lexical processing. In the mental lexicon, a
      word such as CAN has high closeness centrality, because it is close to many other
      words in the lexicon. Whereas, a word such as CURE has low closeness centrality
      because it is far from other words in the lexicon. In an auditory lexical
      decision task (Experiment 1) participants responded more quickly to words with
      high closeness centrality. In Experiment 2 an auditory lexical decision task was
      again used, but with a wider range of stimulus characteristics. Although, there
      was no main effect of closeness centrality in Experiment 2, an interaction
      between closeness centrality and frequency of occurrence was observed on reaction
      times. The results are explained in terms of partial activation gradually
      strengthening over time word-forms that are centrally located in the phonological
      network.

PMID- 29018397
TI  - Short-term Beneficial Effects of 12 Sessions of Neurofeedback on Avoidant
      Personality Accentuation in the Treatment of Alcohol Use Disorder.
AB  - This study evaluated the effects of alpha/theta neurofeedback on Clinical
      Personality Accentuations in individuals with alcohol use disorder. Twenty-five
      males were investigated using a pre-test/post-test design with a waiting-list
      control group. Participants were randomly assigned either to an experimental
      group (n = 13) receiving 12 sessions of neurofeedback twice a week as a treatment
      adjunct over a period of 6 weeks, or to a control group (n = 12) receiving
      treatment as usual. The Inventory of Clinical Personality Accentuations and the
      NEO-Five-Factor Inventory were applied at pre- and post-test. The neurofeedback
      protocol focused on enhancement of the EEG alpha (8-12 Hz) and theta (4-7 Hz) and
      used a visual feedback paradigm. Analyses of covariance showed improvements in
      Avoidant Personality Accentuation within the experimental group. Our data suggest
      that 12 sessions of this neurofeedback intervention might be effective in
      reducing avoidant and stress-related personality traits in patients with alcohol
      use disorder.

PMID- 29018398
TI  - An Assessment of the Dimensionality and Factorial Structure of the Revised
      Paranormal Belief Scale.
AB  - Since its introduction, the Revised Paranormal Belief Scale (RPBS) has developed
      into a principal measure of belief in the paranormal. Accordingly, the RPBS
      regularly appears within parapsychological research. Despite common usage,
      academic debates continue to focus on the factorial structure of the RPBS and its
      psychometric integrity. Using an aggregated heterogeneous sample (N = 3,764), the
      present study tested the fit of 10 factorial models encompassing variants of the
      most commonly proposed solutions (seven, five, two, and one-factor) plus new
      bifactor alternatives. A comparison of competing models revealed a seven-factor
      bifactor solution possessed superior data-model fit (CFI = 0.945, TLI = 0.933,
      IFI = 0.945, SRMR = 0.046, RMSEA = 0.058), containing strong factor loadings for
      a general factor and weaker, albeit acceptable, factor loadings for seven
      subfactors. This indicated that belief in the paranormal, as measured by the
      RPBS, is best characterized as a single overarching construct, comprising several
      related, but conceptually independent subfactors. Furthermore, women reported
      significantly higher paranormal belief scores than men, and tests of invariance
      indicated that mean differences in gender are unlikely to reflect measurement
      bias. Results indicate that despite concerns about the content and psychometric
      integrity of the RPBS the measure functions well at both a global and seven
      factor level. Indeed, the original seven-factors contaminate alternative
      solutions.

PMID- 29018399
TI  - Therapeutic Interventions for Vascular Parkinsonism: A Systematic Review and Meta
      analysis.
AB  - BACKGROUND: Vascular parkinsonism (VP) is defined as the presence of parkinsonian
      syndrome, evidence of cerebrovascular disease, and an established relationship
      between the two disorders. However, the diagnosis of VP is problematic,
      particularly for the clinician confronted with moving from diagnosis to
      treatment. Given the different criteria used in the diagnosis of VP, the
      effectiveness of available therapeutic interventions for this disease are
      currently unknown. METHODS: To assess the clinical response of all published
      therapeutic interventions for VP that have been reported in the literature, we
      conducted a systematic review looking for VP subjects treated with any
      therapeutic intervention. To clarify the prevalence of responsiveness to levodopa
      among VP subjects, we conducted a meta-analysis of 17 observational studies
      retrieved with the search criteria of our review. Also, four studies were
      included in a second analysis to explore if nigrostriatal lesion affected the
      prevalence of levodopa response in VP subjects. Relevant articles were identified
      from MEDLINE, Scopus, and Web of Science published until June 2017. RESULTS: 436
      non-duplicate citations were identified for screening, 107 articles were assessed
      for eligibility, and only 23 observational studies were included in this review.
      No randomized clinical trials were found. Four different therapies were found in
      the literature; among them, levodopa was the only one repetitively reported. The
      calculated event rate of levodopa response in VP subjects was of 0.304 [95%
      confidence interval (CI) of 0.230-0.388]. The overall odds ratio for good
      response to levodopa in VP with lesion in the nigrostriatal pathway vs. no lesion
      in the nigrostriatal pathway was 15.15 (95% CI: 5.2-44.17). CONCLUSION: Despite
      the lack of randomized controlled trials, results of this systematic review and
      meta-analysis show that VP subjects, as operationally defined here, have a low
      response rate to levodopa; nigrostriatal lesion could be used as a proxy
      predictor of levodopa response in VP subjects. Other therapies seem to be co
      adjuvant. Randomized controlled trials with a clear definition of VP are
      necessary to be able to assign positive or negative predictive values to
      available treatments and to recommend any of the therapeutic interventions for
      these subjects.

PMID- 29018400
TI  - Including a Lower-Extremity Component during Hand-Arm Bimanual Intensive Training
      does not Attenuate Improvements of the Upper Extremities: A Retrospective Study
      of Randomized Trials.
AB  - Hand-Arm Bimanual Intensive Therapy (HABIT) promotes hand function using
      intensive practice of bimanual functional and play tasks. This intervention has
      shown to be efficacious to improve upper-extremity (UE) function in children with
      unilateral spastic cerebral palsy (USCP). In addition to UE function deficits,
      lower-extremity (LE) function and UE-LE coordination are also impaired in
      children with USCP. Recently, a new intervention has been introduced in which the
      LE is simultaneously engaged during HABIT (Hand-Arm Bimanual Intensive Therapy
      Including Lower Extremities; HABIT-ILE). Positive effects of this therapy have
      been demonstrated for both the UE and LE function in children with USCP. However,
      it is unknown whether the addition of this constant LE component during a
      bimanual intensive therapy attenuates UE improvements observed in children with
      USCP. This retrospective study, based on multiple randomized protocols, aims to
      compare the UE function improvements in children with USCP after HABIT or HABIT
      ILE. This study included 86 children with USCP who received 90 h of either HABIT
      (n = 42) or HABIT-ILE (n = 44) as participants in previous studies. Children were
      assessed before, after, and 4-6 months after intervention. Primary outcomes were
      the ABILHAND-Kids and the Assisting Hand Assessment. Secondary measures included
      the Jebsen-Taylor Test of Hand Function, the Pediatric Evaluation of Disability
      Inventory [(PEDI); only the self-care functional ability domain] and the Canadian
      Occupational Performance Measure (COPM). Data analysis was performed using two
      way repeated-measures analysis of variance with repeated measures on test
      sessions. Both groups showed similar, significant improvements for all tests
      (test session effect p < 0.001; group * test session interaction p > 0.05) except
      the PEDI and COPM. Larger improvements on these tests were found for the HABIT
      ILE group (test session effect p < 0.001; group * test session interaction p <
      0.05). These larger improvements may be explained by the constant simultaneous UE
      LE engagement observed during the HABIT-ILE intervention since many daily living
      activities included in the PEDI and the COPM goals involve the LE and, more
      specifically, UE-LE coordination. We conclude that UE improvements in children
      with USCP are not attenuated by simultaneous UE-LE engagement during intensive
      intervention. In addition, systematic LE engagement during bimanual intensive
      intervention (HABIT-ILE) leads to larger functional improvements in activities of
      daily living involving the LE.

PMID- 29018401
TI  - Risk Factors and Clinical Manifestations of Juxtacortical Small Lesions: A
      Neuroimaging Study.
AB  - BACKGROUND AND OBJECTIVE: White matter hyperintensities can be easily identified
      by brain imaging. Juxtacortical small lesion (JCSL) is a special type of white
      matter lesion, defined as no greater than 5 mm in diameter and adjacent to the
      cerebral cortex in location. We notice lately that JCSLs alone may be associated
      to various neurological symptoms. Here, we design the present study to determine
      the risk factors for JCSLs and their clinical manifestations in patients in our
      neurology clinic. METHODS: 206 participants suffered from neurological disorders
      and completed magnetic resonance imaging (MRI) examinations were divided into two
      groups: patients with JCSLs and patients without lesions on MRI. Meanwhile, 129
      age- and sex-matched healthy volunteers were also recruited. Laboratory
      examinations and the phenotypes and distributions of the symptoms of the three
      groups were compared. RESULTS: The serum levels of apoB and homocysteine (HCY)
      were independently related to the appearance of JCSLs and HCY level was also
      associated with the number of JCSLs. Patients with JCSLs might present with
      headache, insomnia, and/or anxiety/depression, which were related with the
      anatomical locations of the lesions. CONCLUSION: These data suggest that JCSLs
      are symptomatic and might in result fromarteriole atherosclerosis, which should
      raise our attention.

PMID- 29018402
TI  - Preferential Impairment of the Contralesional Posterior Semicircular Canal in
      Internuclear Ophthalmoplegia.
AB  - BACKGROUND: The vertical vestibulo-ocular reflex (VOR) may be impaired in
      internuclear ophthalmoplegia (INO) as the medial longitudinal fasciculus (MLF)
      conveys VOR-signals from the vertical semicircular canals. It has been proposed
      that signals from the contralesional posterior semicircular canal (PSC) are
      exclusively transmitted through the MLF, while for the contralesional anterior
      canal other pathways exist. OBJECTIVE: Here, we aimed to characterize dysfunction
      in individual canals in INO-patients using the video-head-impulse test (vHIT) and
      to test the hypothesis of dissociated vertical canal impairment in INO. METHODS:
      Video-head-impulse testing and magnetic resonance imaging were obtained in 21
      consecutive patients with unilateral (n = 16) or bilateral (n = 5) INO and 42
      controls. VOR-gains and compensatory catch-up saccades were analyzed and the
      overall function (normal vs. impaired) of each semicircular canal was rated.
      RESULTS: In unilateral INO, largest VOR-gain reductions were noted in the
      contralesional PSC (0.55 +/- 0.11 vs. 0.89 +/- 0.08, p < 0.001), while in
      bilateral INO both posterior (0.43 +/- 0.11 vs. 0.89 +/- 0.08, p < 0.001) and
      anterior (0.58 +/- 0.19 vs. 0.88 +/- 0.09, p < 0.001) canals showed marked drops.
      Small, but significant VOR-gain reductions were also found in the other canals in
      unilateral and bilateral INO-patients. Impairment of overall canal function was
      restricted to the contralesional posterior canal in 60% of unilateral INO
      patients, while isolated involvement of the posterior canal was rare in bilateral
      INO-patients (20%). Reviewers correctly identified the INO-pattern in 15/21 (71%)
      patients and in all controls (sensitivity = 84.2% [95%-CI = 0.59.5-95.8];
      specificity = 95.5% [95%-CI = 83.3-99.2]). CONCLUSION: Using a vHIT based overall
      rating of canal function, the correct INO-pattern could be identified with high
      accuracy. The predominant and often selective impairment of the contralesional
      posterior canal in unilateral INO further supports the role of the MLF in
      transmitting posterior canal signals. In patients with acute dizziness and
      abnormal vHIT-results, central pathologies such as INO should be considered as
      well, especially when the posterior canal is involved.

PMID- 29018403
TI  - Repulsive Guidance Molecule a Inhibits Angiogenesis by Downregulating VEGF and
      Phosphorylated Focal Adhesion Kinase In Vitro.
AB  - Repulsive guidance molecule a (RGMa) is a major neuron guidance factor in central
      nervous systems. We previously found that inhibition of RGMa could greatly
      enhance neural function rehabilitation in rats after MCAO/reperfusion. Neuron
      guidance factors are often regulators of angiogenesis. However, the effect of
      RGMa on angiogenesis and its mechanisms remain to be determined. Here, we
      investigated the effect of RGMa on endothelial cell (EC) proliferation,
      migration, tube formation, and cytoskeleton reassembly. The addition of
      recombinant RGMa significantly decreased the proliferation, migration, and tube
      formation of ECs. It also decreased the level of phosphorylated focal adhesion
      kinase (p-FAK Tyr397). Furthermore, the F-actin of the cytoskeleton assembly was
      obviously suppressed, with decreased filopodia and lamellipodia after the
      addition of RGMa. Knockout of neogenin or Unc5b significantly diminished RGMa's
      inhibition of EC migration, tube formation, and cytoskeleton reassembly. RGMa
      induced p-FAK (Tyr397) decrease was also abolished by knockout of neogenin or
      Unc5b. These results indicate that RGMa may be a negative regulator of
      angiogenesis through downregulating VEGF and p-FAK (Tyr397) via neogenin and
      Unc5b in vitro.

PMID- 29018404
TI  - Socioeconomic Outcome and Quality of Life in Adults after Status Epilepticus: A
      Multicenter, Longitudinal, Matched Case-Control Analysis from Germany.
AB  - BACKGROUND: There is a lack of data concerning socioeconomic outcome and quality
      of life (QoL) in patients after status epilepticus (SE) in Germany. PATIENTS AND
      METHODS: Adult patients treated between 2011 and 2015 due to SE at the university
      hospitals in Frankfurt, Greifswald, and Marburg were asked to fill out a
      questionnaire regarding long-term outcome of at least 3 months after discharge.
      The SE cohort consisted of 25.9% patients with an acute symptomatic, 42% with a
      remote symptomatic and previous epilepsy, 22.2% with a new-onset remote
      symptomatic, and 9.9% with other or unknown etiology. A matched case-control
      analysis was applied for comparison with patients with drug refractory epilepsy
      and seizure remission, both not previously affected by SE. RESULTS: A total of 81
      patients (mean age: 58.7 +/- 18.0 years; 58% female) participated. A non
      refractory course was present in 59.3%, while 27.2% had a refractory SE (RSE) and
      13.6% had a superrefractory SE (SRSE). Before admission, a favorable modified
      Rankin Scale (mRS) of 0-3 was found in 82.7% (67/81), deteriorating to 38.3%
      (31/81) (p = 0.003) at discharge. The majority returned home [51.9% (42/81)],
      32.1% entered a rehabilitation facility, while 12.3% were transferred to a
      nursing home and 3.7% to another hospital. The overall mRS at follow-up did not
      change; 61.8% (45/74) reached an mRS of 0-3. In RSE and SRSE, the proportion with
      a favorable mRS increased from 45.5% at discharge to 70% at follow-up, while QoL
      was comparable to a non-refractory SE course. Matched epilepsy controls in
      seizure remission were treated with a lower mean number of anticonvulsants (1.3
      +/- 0.7) compared to controls with drug refractory epilepsy (1.9 +/- 0.8; p <
      0.001) or SE (1.9 +/- 1.1; p < 0.001). A major depression was found in 32.8% of
      patients with SE and in 36.8% of drug refractory epilepsy, but only in 20.3% of
      patients in seizure remission. QoL was reduced in all categories (QOLIE-31) in SE
      patients in comparison with patients in seizure remission, but was comparable to
      patients with drug refractory epilepsy. DISCUSSION: Patients after SE show
      substantial impairments in their QoL and daily life activities. However, in the
      long term, patients with RSE and SRSE had a relatively favorable outcome
      comparable to that of patients with a non-refractory SE course. This underlines
      the need for efficient therapeutic options in SE.

PMID- 29018405
TI  - Chimeric Peptide Tat-HA-NR2B9c Improves Regenerative Repair after Transient
      Global Ischemia.
AB  - Transient global ischemia (TGI) is a major public health problem, and it
      heightens the need of effective treatments. The present study was undertaken to
      investigate whether recombinant polypeptide Tat-HA-NR2B9c improves spatial
      learning and memory deficits in rats after TGI. Rats were subjected to 20-min
      ischemia induced by four-vessel occlusion (4-VO) method and daily injected with
      Tat-HA-NR2B9c (1.12 mg/kg) for 1 week. Tat-HA-NR2B9c increased CREB activity,
      upregulated B-cell lymphoma-2 (Bcl-2) expression after treated for 24 h. There
      was a significant increase in dendrite spine density in hippocampal CA1 region
      and BrdU-positive cells and BrdU/NeuN-positive cells in the dentate gyrus after
      Tat-HA-NR2B9c treatment, compared with ischemia group at postischemic day 28.
      Inhibition of the CREB activation by recombinant lentivirus, LV-CREB133-GFP,
      abolished the upregulation effects of Tat-HA-NR2B9c on Bcl-2 expression.
      Moreover, Tat-HA-NR2B9c improved the impaired spatial learning and memory ability
      in Morris water maze. These results suggest that Tat-HA-NR2B9c substantially
      ameliorated the TGI-induced loss of dendrite spine in hippocampal CA1, increased
      neurogenesis in dentate gyrus, and significantly improved cognitive abilities by
      the CREB pathway in rats after transient global cerebral ischemia. It may be
      served as a treatment for TGI.

PMID- 29018406
TI  - Editorial: Karolinska Institutet 200-Year Anniversary Symposium on Injuries to
      the Spinal Cord and Peripheral Nervous System-An Update on Recent Advances in
      Regenerative Neuroscience.

PMID- 29018407
TI  - Dose-Dependent and Lasting Influences of Intranasal Vasopressin on Face
      Processing in Men.
AB  - Arginine vasopressin (AVP) and related peptides have diverse effects on social
      behaviors in vertebrates, sometimes promoting affiliative interactions and
      sometimes aggressive or antisocial responses. The type of influence, in at least
      some species, depends on social contexts, including the sex of the individuals in
      the interaction and/or on the levels of peptide within brain circuits that
      control the behaviors. To determine if AVP promotes different responses to same-
      and other-sex faces in men, and if those effects are dose dependent, we measured
      the effects of two doses of AVP on subjective ratings of male and female faces.
      We also tested if any influences persist beyond the time of drug delivery. When
      AVP was administered intranasally on an initial test day, 20 IU was associated
      with decreased social assessments relative to placebo and 40 IU, and some of the
      effects persisted beyond the initial drug delivery and appeared to generalize to
      novel faces on subsequent test days. In single men, those influences were most
      pronounced, but not exclusive, for male faces, whereas in coupled men they were
      primarily associated with responses to female faces. Similar influences were not
      observed if AVP was delivered after placebo on a second test day. In a
      preliminary analysis, the differences in social assessments observed between men
      who received 20 and 40 IU, which we suggest primarily reflect lowered social
      assessments induced by the lower dose, appeared most pronounced in subjects who
      carry what has been identified as a risk allele for the V1a receptor gene.
      Together, these results suggest that AVP's effects on face processing, and
      possibly other social responses, differ according to dose, depend on relationship
      status, and may be more prolonged than previously recognized.

PMID- 29018408
TI  - Levels of Hepatic Activating Transcription Factor 6 and Caspase-3 Are
      Downregulated in Mice after Excessive Training.
AB  - Recently, we demonstrated that different running overtraining (OT) protocols with
      the same external load, but performed downhill (OTR/down), uphill (OTR/up), and
      without inclination (OTR), led to hepatic fat accumulation. As the disruption of
      endoplasmic reticulum (ER) homeostasis is linked to animal models of fatty liver
      disease, we investigated the effects of these OT models on the proteins related
      to ER stress (i.e., BiP, inositol-requiring enzyme 1, protein kinase RNA-like
      endoplasmic reticulum kinase, eIF2alpha, ATF6beta, and glucose-regulated protein
      94) and apoptosis (C/EBP-homologous protein, Caspase-3, 4, and 12, Bax, and tumor
      necrosis factor receptor-associated factor 2) in livers of C57BL/6 mice. Also,
      aerobic training can attenuate cardiac ER stress and improve exercise capacity.
      Therefore, we investigated whether the decrease in performance induced by our OT
      protocols is linked to ER stress and apoptosis in mouse hearts. The rodents were
      divided into six groups: naive (N, sedentary mice), control (CT, sedentary mice
      submitted to the performance evaluations), trained (TR), OTR/down, OTR/up, and
      OTR groups. Rotarod, incremental load, exhaustive, and grip force tests were used
      to evaluate performance. After the grip force test, the livers and cardiac
      muscles (i.e., left ventricle) were removed and used for immunoblotting. All of
      the OT protocols led to similar responses in the performance parameters and
      displayed significantly lower hepatic ATF6beta values compared to the N group.
      The OTR/down group exhibited lower liver cleaved caspase-3 values compared to the
      CT group. However, the other proteins related to ER stress and apoptosis were not
      modulated. Also, the cardiac proteins related to ER stress and apoptosis were not
      modulated in the experimental groups. In conclusion, the OT protocols decreased
      the levels of hepatic ATF6beta, and the OTR/down group decreased the levels of
      hepatic cleaved caspase-3. Also, the decrease in performance induced by our OT
      models is not associated with ER stress and apoptosis in mice hearts.

PMID- 29018409
TI  - Innate Viral Receptor Signaling Determines Type 1 Diabetes Onset.
AB  - Heritable susceptibility of the autoimmune disorder, type 1 diabetes (T1D), only
      partially equates for the incidence of the disease. Significant evidence
      attributes several environmental stressors, such as vitamin D deficiency, gut
      microbiome, dietary antigens, and most notably virus infections in triggering the
      onset of T1D in these genetically susceptible individuals. Extensive
      epidemiological and clinical studies have provided credibility to this causal
      relationship. Infection by the enterovirus, coxsackievirus B, has been closely
      associated with onset of T1D and is considered a significant etiological agent
      for disease induction. Recognition of viral antigens via innate pathogen
      recognition receptors induce inflammatory events which contribute to
      autoreactivity of pancreatic self-antigens and ultimately the destruction of
      insulin-secreting beta cells. The activation of these specific innate pathways
      and expression of inflammatory molecules, including type I and III interferon,
      prime the immune system to elicit either a protective regulatory response or a
      diabetogenic effector response. Therefore, sensing of viral antigens by retinoic
      acid-inducible gene I-like receptors and toll-like receptors may be detrimental
      to inducing autoreactivity initiated by viral stress and resulting in T1D.

PMID- 29018411
TI  - The Oleaginous Yeast Meyerozyma guilliermondii BI281A as a New Potential
      Biodiesel Feedstock: Selection and Lipid Production Optimization.
AB  - A high throughput screening (HTS) methodology for evaluation of cellular lipid
      content based on Nile red fluorescence reads using black background 96-wells test
      plates and a plate reader equipment allowed the rapid intracellular lipid
      estimation of strains from a Brazilian phylloplane yeast collection. A new
      oleaginous yeast, Meyerozyma guilliermondii BI281A, was selected, for which the
      gravimetric determination of total lipids relative to dry weight was 52.38% for
      glucose or 34.97% for pure glycerol. The lipid production was optimized obtaining
      108 mg/L of neutral lipids using pure glycerol as carbon source, and the strain
      proved capable of accumulating oil using raw glycerol from a biodiesel refinery.
      The lipid profile showed monounsaturated fatty acids (MUFA) varying between 56 or
      74% in pure or raw glycerol, respectively. M. guilliermondii BI281A bears
      potential as a new biodiesel feedstock.

PMID- 29018410
TI  - Next-Generation Beneficial Microbes: The Case of Akkermansia muciniphila.
AB  - Metabolic disorders associated with obesity and cardiometabolic disorders are
      worldwide epidemic. Among the different environmental factors, the gut microbiota
      is now considered as a key player interfering with energy metabolism and host
      susceptibility to several non-communicable diseases. Among the next-generation
      beneficial microbes that have been identified, Akkermansia muciniphila is a
      promising candidate. Indeed, A. muciniphila is inversely associated with obesity,
      diabetes, cardiometabolic diseases and low-grade inflammation. Besides the
      numerous correlations observed, a large body of evidence has demonstrated the
      causal beneficial impact of this bacterium in a variety of preclinical models.
      Translating these exciting observations to human would be the next logic step and
      it now appears that several obstacles that would prevent the use of A.
      muciniphila administration in humans have been overcome. Moreover, several lines
      of evidence indicate that pasteurization of A. muciniphila not only increases its
      stability but more importantly increases its efficacy. This strongly positions A.
      muciniphila in the forefront of next-generation candidates for developing novel
      food or pharma supplements with beneficial effects. Finally, a specific protein
      present on the outer membrane of A. muciniphila, termed Amuc_1100, could be
      strong candidate for future drug development. In conclusion, as plants and its
      related knowledge, known as pharmacognosy, have been the source for designing
      drugs over the last century, we propose that microbes and microbiomegnosy, or
      knowledge of our gut microbiome, can become a novel source of future therapies.

PMID- 29018412
TI  - A Novel Lactobacilli-Based Teat Disinfectant for Improving Bacterial Communities
      in the Milks of Cow Teats with Subclinical Mastitis.
AB  - Teat disinfection pre- and post-milking is important for the overall health and
      hygiene of dairy cows. The objective of this study was to evaluate the efficacy
      of a novel probiotic lactobacilli-based teat disinfectant based on changes in
      somatic cell count (SCC) and profiling of the bacterial community. A total of 69
      raw milk samples were obtained from eleven Holstein-Friesian dairy cows over 12
      days of teat dipping in China. Single molecule, real-time sequencing technology
      (SMRT) was employed to profile changes in the bacterial community during the
      cleaning protocol and to compare the efficacy of probiotic lactic acid bacteria
      (LAB) and commercial teat disinfectants. The SCC gradually decreased following
      the cleaning protocol and the SCC of the LAB group was slightly lower than that
      of the commercial disinfectant (CD) group. Our SMRT sequencing results indicate
      that raw milk from both the LAB and CD groups contained diverse microbial
      populations that changed over the course of the cleaning protocol. The relative
      abundances of some species were significantly changed during the cleaning
      process, which may explain the observed bacterial community differences.
      Collectively, these results suggest that the LAB disinfectant could reduce
      mastitis-associated bacteria and improve the microbial environment of the cow
      teat. It could be used as an alternative to chemical pre- and post-milking teat
      disinfectants to maintain healthy teats and udders. In addition, the Pacific
      Biosciences SMRT sequencing with the full-length 16S ribosomal RNA gene was shown
      to be a powerful tool for monitoring changes in the bacterial population during
      the cleaning protocol.

PMID- 29018413
TI  - Effect of the Ethyl Acetate Fraction of Eugenia uniflora on Proteins Global
      Expression during Morphogenesis in Candida albicans.
AB  - Candida albicans is able to switch from yeast to hyphal growth and this is an
      essential step for tissue invasion and establishment of infection. Due to the
      limited drug arsenal used to treat fungal infections and the constant emergence
      of resistant strains, it is important to search for new therapeutic candidates.
      Therefore, this study aimed to investigate by proteomic analysis the role of a
      natural product (Eugenia uniflora) in impairing hypha formation in C. albicans.
      We also tested the potential action of E. uniflora to prevent and treat oral
      candidiasis induced in a murine model of oral infection and the ability of
      polymorphonuclear neutrophils to phagocytize C. albicans cells treated with the
      ethyl acetate fraction of the extract. We found that this fraction greatly
      reduced hypha formation after morphogenesis induction in the presence of serum.
      Besides, several proteins were differentially expressed in cells treated with the
      fraction. Surprisingly, the ethyl acetate fraction significantly reduced
      phagocytosis in C. albicans (Mean 120.36 +/- 36.71 yeasts/100 PMNs vs. 44.68 +/-
      19.84 yeasts/100 PMNs). Oral candidiasis was attenuated when C. albicans cells
      were either pre-incubated in the presence of E. uniflora or when the fraction was
      applied to the surface of the oral cavity after infection. These results were
      consistent with the reduction in CFU counts (2.36 vs. 1.85 Log10 CFU/ml) and
      attenuation of tissue damage observed with histopathological analysis of animals
      belonging to treated group. We also observed shorter true hyphae by direct
      examination and histopathological analysis, when cells were treated with the
      referred natural product. The E. uniflora ethyl acetate fraction was non-toxic to
      human cells. E. uniflora may act on essential proteins mainly related to cellular
      structure, reducing the capacity of filamentation and attenuating infection in a
      murine model, without causing any toxic effect on human cells, suggesting that it
      may be a future therapeutic alternative for the treatment of Candida infections.

PMID- 29018414
TI  - Development of a Click Beetle Luciferase Reporter System for Enhanced
      Bioluminescence Imaging of Listeria monocytogenes: Analysis in Cell Culture and
      Murine Infection Models.
AB  - Listeria monocytogenes is a Gram-positive facultative intracellular pathogen that
      is widely used as a model organism for the analysis of infection biology. In this
      context, there is a current need to develop improved reporters for enhanced
      bioluminescence imaging (BLI) of the pathogen in infection models. We have
      developed a click beetle red luciferase (CBR-luc) based vector (pPL2CBRopt)
      expressing codon optimized CBR-luc under the control of a highly expressed
      Listerial promoter (PHELP) for L. monocytogenes and have compared this to a lux
      based system expressing bacterial luciferase for BLI of the pathogen using in
      vitro growth experiments and in vivo models. The CBR-luc plasmid stably
      integrates into the L. monocytogenes chromosome and can be used to label field
      isolates and laboratory strains of the pathogen. Growth experiments revealed that
      CBR-luc labeled L. monocytogenes emits a bright signal in exponential phase that
      is maintained during stationary phase. In contrast, lux-labeled bacteria produced
      a light signal that peaked during exponential phase and was significantly reduced
      during stationary phase. Light from CBR-luc labeled bacteria was more efficient
      than the signal from lux-labeled bacteria in penetrating an artificial tissue
      depth assay system. A cell invasion assay using C2Bbe1 cells and a systemic
      murine infection model revealed that CBR-luc is suited to BLI approaches and
      demonstrated enhanced sensitivity relative to lux in the context of Listeria
      infection models. Overall, we demonstrate that this novel CBR reporter system
      provides efficient, red-shifted light production relative to lux and may have
      significant applications in the analysis of L. monocytogenes pathogenesis.

PMID- 29018415
TI  - Time to Go Back to the Original Name.

PMID- 29018416
TI  - Transcriptomic Analysis of the Adaptation of Listeria monocytogenes to Lagoon and
      Soil Matrices Associated with a Piggery Environment: Comparison of Expression
      Profiles.
AB  - Understanding how Listeria monocytogenes, the causative agent of listeriosis,
      adapts to the environment is crucial. Adaptation to new matrices requires
      regulation of gene expression. To determine how the pathogen adapts to lagoon
      effluent and soil, two matrices where L. monocytogenes has been isolated, we
      compared the transcriptomes of L. monocytogenes CIP 110868 20 min and 24 h after
      its transfer to effluent and soil extract. Results showed major variations in the
      transcriptome of L. monocytogenes in the lagoon effluent but only minor
      modifications in the soil. In both the lagoon effluent and in the soil, genes
      involved in mobility and chemotaxis and in the transport of carbohydrates were
      the most frequently represented in the set of genes with higher transcript
      levels, and genes with phage-related functions were the most represented in the
      set of genes with lower transcript levels. A modification of the cell envelop was
      only found in the lagoon environment. Finally, the differential analysis included
      a large proportion of regulators, regulons, and ncRNAs.

PMID- 29018418
TI  - Microbial Diversity in a Hypersaline Sulfate Lake: A Terrestrial Analog of
      Ancient Mars.
AB  - Life can persist under severe osmotic stress and low water activity in
      hypersaline environments. On Mars, evidence for the past presence of saline
      bodies of water is prevalent and resulted in the widespread deposition of sulfate
      and chloride salts. Here we investigate Spotted Lake (British Columbia, Canada),
      a hypersaline lake with extreme (>3 M) levels of sulfate salts as an exemplar of
      the conditions thought to be associated with ancient Mars. We provide the first
      characterization of microbial structure in Spotted Lake sediments through
      metagenomic sequencing, and report a bacteria-dominated community with abundant
      Proteobacteria, Firmicutes, and Bacteroidetes, as well as diverse extremophiles.
      Microbial abundance and functional comparisons reveal similarities to Ace Lake, a
      meromictic Antarctic lake with anoxic and sulfidic bottom waters. Our analysis
      suggests that hypersaline-associated species occupy niches characterized foremost
      by differential abundance of Archaea, uncharacterized Bacteria, and
      Cyanobacteria. Potential biosignatures in this environment are discussed,
      specifically the likelihood of a strong sulfur isotopic fractionation record
      within the sediments due to the presence of sulfate reducing bacteria. With its
      high sulfate levels and seasonal freeze-thaw cycles, Spotted Lake is an analog
      for ancient paleolakes on Mars in which sulfate salt deposits may have offered
      periodically habitable environments, and could have concentrated and preserved
      organic materials or their biomarkers over geologic time.

PMID- 29018417
TI  - Molecular Mechanisms That Contribute to Horizontal Transfer of Plasmids by the
      Bacteriophage SPP1.
AB  - Natural transformation and viral-mediated transduction are the main avenues of
      horizontal gene transfer in Firmicutes. Bacillus subtilis SPP1 is a generalized
      transducing bacteriophage. Using this lytic phage as a model, we have analyzed
      how viral replication and recombination systems contribute to the transfer of
      plasmid-borne antibiotic resistances. Phage SPP1 DNA replication relies on
      essential phage-encoded replisome organizer (G38P), helicase loader (G39P),
      hexameric replicative helicase (G40P), recombinase (G35P) and in less extent on
      the partially dispensable 5'->3' exonuclease (G34.1P), the single-stranded DNA
      binding protein (G36P) and the Holliday junction resolvase (G44P).
      Correspondingly, the accumulation of linear concatemeric plasmid DNA, and the
      formation of transducing particles were blocked in the absence of G35P, G38P,
      G39P, and G40P, greatly reduced in the G34.1P, G36P mutants, and slightly reduced
      in G44P mutants. In contrast, establishment of injected linear plasmid DNA in the
      recipient host was independent of viral-encoded functions. DNA homology between
      SPP1 and the plasmid, rather than a viral packaging signal, enhanced the
      accumulation of packagable plasmid DNA. The transfer efficiency was also
      dependent on plasmid copy number, and rolling-circle plasmids were encapsidated
      at higher frequencies than theta-type replicating plasmids.

PMID- 29018419
TI  - Gene Expression Response of Salmonella enterica Serotype Enteritidis Phage Type 8
      to Subinhibitory Concentrations of the Plant-Derived Compounds Trans
      Cinnamaldehyde and Eugenol.
AB  - Background:Salmonella Enteritidis phage type 8 (PT8) is a major poultry
      associated Salmonella strain implicated in foodborne outbreaks in the United
      States. We previously reported that two plant-derived compounds generally
      recognized as safe (GRAS), trans-cinnamaldehyde (TC), and eugenol (EG),
      significantly reduced S. Enteritidis colonization in broiler and layer chickens.
      To elucidate potential PT8 genes affected by TC and EG during colonization, a
      whole-genome microarray analysis of the bacterium treated with TC and EG was
      conducted. Results:S. Enteritidis PT8 was grown in Luria-Bertani broth at 37
      degrees C to an OD600 of ~0.5. Subinhibitory concentrations (SICs; concentration
      that does not inhibit bacterial growth) of TC (0.01%; 0.75 mM) or EG (0.04%; 2.46
      mM) were then added to the culture. S. Enteritidis PT8 RNA was extracted before
      and 30 min after TC or EG addition. Labeled cDNA from three replicate experiments
      was subsequently hybridized to a microarray of over 99% of S. Enteritidis PT4
      genes, and the hybridization signals were quantified. The plant-derived compounds
      down-regulated (P < 0.005) expression of S. Enteritidis PT8 genes involved in
      flagellar motility, regulation of the Salmonella Pathogenicity Island 1, and
      invasion of intestinal epithelial cells. TC and EG also suppressed transcription
      of genes encoding multiple transport systems and outer membrane proteins.
      Moreover, several metabolic and biosynthetic pathways in the pathogen were down
      regulated during exposure to the plant-derived compounds. Both TC and EG
      stimulated the transcription of heat shock genes, such as dnaK, dnaJ, ibpB, and
      ibpA in S. Enteritidis PT8 (P < 0.005). The results obtained from microarray were
      validated using a quantitative real-time PCR. Conclusion: The plant-derived
      compounds TC and EG exert antimicrobial effects on S. Enteritidis PT8 by
      affecting multiple genes, including those associated with virulence,
      colonization, cell membrane composition, and transport systems.

PMID- 29018420
TI  - Molecular Characterization of Reduced Susceptibility to Biocides in Clinical
      Isolates of Acinetobacter baumannii.
AB  - Active efflux is regarded as a common mechanism for antibiotic and biocide
      resistance. However, the role of many drug efflux pumps in biocide resistance in
      Acinetobacter baumannii remains unknown. Using biocide-resistant A. baumannii
      clinical isolates, we investigated the incidence of 11 known/putative
      antimicrobial resistance efflux pump genes (adeB, adeG, adeJ, adeT1, adeT2, amvA,
      abeD, abeM, qacE, qacEDelta1, and aceI) and triclosan target gene fabI through
      PCR and DNA sequencing. Reverse transcriptase quantitative PCR was conducted to
      assess the correlation between the efflux pump gene expression and the reduced
      susceptibility to triclosan or chlorhexidine. The A. baumannii isolates displayed
      high levels of reduced susceptibility to triclosan, chlorhexidine, benzalkonium,
      hydrogen peroxide, and ethanol. Most tested isolates were resistant to multiple
      antibiotics. Efflux resistance genes were widely distributed and generally
      expressed in A. baumannii. Although no clear relation was established between
      efflux pump gene expression and antibiotic resistance or reduced biocide
      susceptibility, triclosan non-susceptible isolates displayed relatively increased
      expression of adeB and adeJ whereas chlorhexidine non-susceptible isolates had
      increased abeM and fabI gene expression. Increased expression of adeJ and abeM
      was also demonstrated in multiple antibiotic resistant isolates. Exposure of
      isolates to subinhibitory concentrations of triclosan or chlorhexidine induced
      gene expression of adeB, adeG, adeJ and fabI, and adeB, respectively. A point
      mutation in FabI, Gly95Ser, was observed in only one triclosan-resistant isolate.
      Multiple sequence types with the major clone complex, CC92, were identified in
      high level triclosan-resistant isolates. Overall, this study showed the high
      prevalence of antibiotic and biocide resistance as well as the complexity of
      intertwined resistance mechanisms in clinical isolates of A. baumannii, which
      highlights the importance of antimicrobial stewardship and resistance
      surveillance in clinics.

PMID- 29018421
TI  - Himar1 Transposon for Efficient Random Mutagenesis in Aggregatibacter
      actinomycetemcomitans.
AB  - Aggregatibacter actinomycetemcomitans is the primary etiological agent of
      aggressive periodontal disease. Identification of novel virulence factors at the
      genome-wide level is hindered by lack of efficient genetic tools to perform
      mutagenesis in this organism. The Himar1 mariner transposon is known to yield a
      random distribution of insertions in an organism's genome with requirement for
      only a TA dinucleotide target and is independent of host-specific factors.
      However, the utility of this system in A. actinomycetemcomitans is unknown. In
      this study, we found that Himar1 transposon mutagenesis occurs at a high
      frequency (*10-4), and can be universally applied to wild-type A.
      actinomycetemcomitans strains of serotypes a, b, and c. The Himar1 transposon
      inserts were stably inherited in A. actinomycetemcomitans transconjugants in the
      absence of antibiotics. A library of 16,000 mutant colonies of A.
      actinomycetemcomitans was screened for reduced biofilm formation. Mutants with
      transposon inserts in genes encoding pilus, putative ion transporters, multidrug
      resistant proteins, transcription regulators and enzymes involved in the
      synthesis of extracellular polymeric substance, bacterial metabolism and stress
      response were discovered in this screen. Our results demonstrated the utility of
      the Himar1 mutagenesis system as a novel genetic tool for functional genomic
      analysis in A. actinomycetemcomitans.

PMID- 29018422
TI  - Novel Aggregation Promoting Factor AggE Contributes to the Probiotic Properties
      of Enterococcus faecium BGGO9-28.
AB  - The understanding of mechanisms of interactions between various bacterial cell
      surface proteins and host receptors has become imperative for the study of the
      health promoting features of probiotic enterococci. This study, for the first
      time, describes a novel enterococcal aggregation protein, AggE, from Enterococcus
      faecium BGGO9-28, selected from a laboratory collection of enterococcal isolates
      with auto-aggregation phenotypes. Among them, En. faecium BGGO9-28 showed the
      strongest auto-aggregation, adhesion to components of ECM and biofilm formation.
      Novel aggregation promoting factor AggE, a protein of 178.1 kDa, belongs to the
      collagen-binding superfamily of proteins and shares similar architecture with
      previously discovered aggregation factors from lactic acid bacteria (LAB). Its
      expression in heterologous enterococcal and lactococcal hosts demonstrates that
      the aggE gene is sufficient for cell aggregation. The derivatives carrying aggE
      exhibited the ten times higher adhesion ability to collagen and fibronectin,
      possess about two times higher adhesion to mucin and contribute to the increase
      of biofilm formation, comparing to the control strains. Analysis for the presence
      of virulence factors (cytolysin and gelatinase production), antibiotic resistance
      (antibiotic susceptibility) and genes (cylA, agg, gelE, esp, hylN, ace, efaAfs ,
      and efaAfm ) showed that BGGO9-28 was sensitive to all tested antibiotics,
      without hemolytic or gelatinase activity. This strain does not carry any of the
      tested genes encoding for known virulence factors. Results showed that BGGO9-28
      was resistant to low pH and high concentrations of bile salts. Also, it adhered
      strongly to the Caco-2 human epithelial cell line. In conclusion, the results of
      this study indicate that the presence of AggE protein on the cell surface in
      enterococci is a desirable probiotic feature.

PMID- 29018423
TI  - The Microbiome of Seriola lalandi of Wild and Aquaculture Origin Reveals
      Differences in Composition and Potential Function.
AB  - Seriola lalandi is an economically important species that is globally distributed
      in temperate and subtropical marine waters. Aquaculture production of this
      species has had problems associated with intensive fish farming, such as disease
      outbreaks or nutritional deficiencies causing high mortalities. Intestinal
      microbiota has been involved in many processes that benefit the host, such as
      disease control, stimulation of the immune response, and the promotion of
      nutrient metabolism, among others. However, little is known about the potential
      functionality of the microbiota and the differences in the composition between
      wild and aquacultured fish. Here, we assayed the V4-region of the 16S rRNA gene
      using high-throughput sequencing. Our results showed that there are significant
      differences between S. lalandi of wild and aquaculture origin (ANOSIM and
      PERMANOVA, P < 0.05). At the genus level, a total of 13 genera were
      differentially represented between the two groups, all of which have been
      described as beneficial microorganisms that have an antagonistic effect against
      pathogenic bacteria, improve immunological parameters and growth performance, and
      contribute to nutrition. Additionally, the changes in the presumptive functions
      of the intestinal microbiota of yellowtail were examined by predicting the
      metagenomes using PICRUSt. The most abundant functional categories were those
      corresponding to the metabolism of cofactors and vitamins, amino acid metabolism
      and carbohydrate metabolism, revealing differences in the contribution of the
      microbiota depending on the origin of the animals. To our knowledge, this is the
      first study to characterize and compare the intestinal microbiota of S. lalandi
      of wild and aquaculture origin using high-throughput sequencing.

PMID- 29018424
TI  - Sample Preservation, DNA or RNA Extraction and Data Analysis for High-Throughput
      Phytoplankton Community Sequencing.
AB  - Phytoplankton is the basis for aquatic food webs and mirrors the water quality.
      Conventionally, phytoplankton analysis has been done using time consuming and
      partly subjective microscopic observations, but next generation sequencing (NGS)
      technologies provide promising potential for rapid automated examination of
      environmental samples. Because many phytoplankton species have tough cell walls,
      methods for cell lysis and DNA or RNA isolation need to be efficient to allow
      unbiased nucleic acid retrieval. Here, we analyzed how two phytoplankton
      preservation methods, three commercial DNA extraction kits and their
      improvements, three RNA extraction methods, and two data analysis procedures
      affected the results of the NGS analysis. A mock community was pooled from
      phytoplankton species with variation in nucleus size and cell wall hardness.
      Although the study showed potential for studying Lugol-preserved sample
      collections, it demonstrated critical challenges in the DNA-based phytoplankton
      analysis in overall. The 18S rRNA gene sequencing output was highly affected by
      the variation in the rRNA gene copy numbers per cell, while sample preservation
      and nucleic acid extraction methods formed another source of variation. At the
      top, sequence-specific variation in the data quality introduced unexpected
      bioinformatics bias when the sliding-window method was used for the quality
      trimming of the Ion Torrent data. While DNA-based analyses did not correlate with
      biomasses or cell numbers of the mock community, rRNA-based analyses were less
      affected by different RNA extraction procedures and had better match with the
      biomasses, dry weight and carbon contents, and are therefore recommended for
      quantitative phytoplankton analyses.

PMID- 29018425
TI  - Phosphorylation of Icariin Can Alleviate the Oxidative Stress Caused by the Duck
      Hepatitis Virus A through Mitogen-Activated Protein Kinases Signaling Pathways.
AB  - The duck virus hepatitis (DVH) caused by the duck hepatitis virus A (DHAV) has
      produced extensive economic losses to the duck industry. The currently licensed
      commercial vaccine has shown some defects and does not completely prevent the
      DVH. Accordingly, a new alternative treatment for this disease is urgently
      needed. Previous studies have shown that icariin (ICA) and its phosphorylated
      derivative (pICA) possessed good anti-DHAV effects through direct and indirect
      antiviral pathways, such as antioxidative stress. But the antioxidant activity
      showed some differences between ICA and pICA. The aim of this study is to prove
      that ICA and pICA attenuate oxidative stress caused by DHAV in vitro and in vivo,
      and to investigate their mechanism of action to explain their differences in
      antioxidant activities. In vivo, the dynamic deaths, oxidative evaluation indexes
      and hepatic pathological change scores were detected. When was added the
      hinokitiol which showed the pro-oxidative effect as an intervention method, pICA
      still possessed more treatment effect than ICA. The strong correlation between
      mortality and oxidative stress proves that ICA and pICA alleviate oxidative
      stress caused by DHAV. This was also demonstrated by the addition of hydrogen
      peroxide (H2O2) as an intervention method in vitro. pICA can be more effective
      than ICA to improve duck embryonic hepatocytes (DEHs) viability and reduce the
      virulence of DHAV. The strong correlation between TCID50 and oxidative stress
      demonstrates that ICA and pICA can achieve anti-DHAV effects by inhibiting
      oxidative stress. In addition, the superoxide dismutase (SOD) and glutathione
      peroxidase (GSH-Px) of ICA and pICA showed significant difference. pICA could
      significantly inhibit the phosphorylation of p38, extra cellular signal regulated
      Kinase (ERK 1/2) and c-Jun N-terminal kinase (JNK), which were related to mitogen
      activated protein kinases (MAPKs) signaling pathways. Ultimately, compared to
      ICA, pICA exhibited more antioxidant activity that could regulate oxidative
      stress-related indicators, and inhibited the phosphorylation of MAPKs signaling
      pathway.

PMID- 29018426
TI  - Transfer and Persistence of a Multi-Drug Resistance Plasmid in situ of the Infant
      Gut Microbiota in the Absence of Antibiotic Treatment.
AB  - The microbial ecosystem residing in the human gut is believed to play an
      important role in horizontal exchange of virulence and antibiotic resistance
      genes that threatens human health. While the diversity of gut-microorganisms and
      their genetic content has been studied extensively, high-resolution insight into
      the plasticity, and selective forces shaping individual genomes is scarce. In a
      longitudinal study, we followed the dynamics of co-existing Escherichia coli
      lineages in an infant not receiving antibiotics. Using whole genome sequencing,
      we observed large genomic deletions, bacteriophage infections, as well as the
      loss and acquisition of plasmids in these lineages during their colonization of
      the human gut. In particular, we captured the exchange of multidrug resistance
      genes, and identified a clinically relevant conjugative plasmid mediating the
      transfer. This resistant transconjugant lineage was maintained for months,
      demonstrating that antibiotic resistance genes can disseminate and persist in the
      gut microbiome; even in absence of antibiotic selection. Furthermore, through in
      vivo competition assays, we suggest that the resistant transconjugant can persist
      through a fitness advantage in the mouse gut in spite of a fitness cost in vitro.
      Our findings highlight the dynamic nature of the human gut microbiota and provide
      the first genomic description of antibiotic resistance gene transfer between
      bacteria in the unperturbed human gut. These results exemplify that conjugative
      plasmids, harboring resistance determinants, can transfer and persists in the gut
      in the absence of antibiotic treatment.

PMID- 29018427
TI  - Human Cytomegalovirus IE2 86 kDa Protein Induces STING Degradation and Inhibits
      cGAMP-Mediated IFN-beta Induction.
AB  - Stimulator of interferon genes (STING) is a critical signaling molecule in the
      innate immune response against DNA viruses by either directly sensing
      intracellular DNA or functioning as an adaptor molecule to activate the type I
      interferon (IFN) signaling pathway. We determined the functional interaction
      between STING and human cytomegalovirus (HCMV). A cDNA library containing 133
      HCMV ORFs was screened to identify viral genes that inhibit STING-induced IFN
      beta promoter activation. Among the screened ORFs, UL122, which encodes the
      immediate-early 2 86 kDa (IE86) protein, strongly abolished STING-induced IFN
      beta promoter activation. Interestingly, IE86 protein facilitated the proteasome
      dependent degradation of STING and inhibited 2'3'-cGAMP-mediated induction of
      IFNB1 and CXCL10. Taken together, this study demonstrates the existence of a post
      translational regulation of STING by HCMV IE86 protein.

PMID- 29018428
TI  - Defining the Genetic Features of O-Antigen Biosynthesis Gene Cluster and
      Performance of an O-Antigen Serotyping Scheme for Escherichia albertii.
AB  - Escherichia albertii is a newly described and emerging diarrheagenic pathogen
      responsible for outbreaks of gastroenteritis. Serotyping plays an important role
      in diagnosis and epidemiological studies for pathogens of public health
      importance. The diversity of O-antigen biosynthesis gene clusters (O-AGCs)
      provides the primary basis for serotyping. However, little is known about the
      distribution and diversity of O-AGCs of E. albertii strains. Here, we presented a
      complete sequence set for the O-AGCs from 52 E. albertii strains and identified
      seven distinct O-AGCs. Six of these were also found in 15 genomes of E. albertii
      strains deposited in the public database. Possession of wzy/wzx genes in each O
      AGC strongly suggest that O-antigens of E. albertii were synthesized by the
      Wzx/Wzy-dependent pathway. Furthermore, we performed an O-antigen serotyping
      scheme for E. albertii based on specific antisera against seven O-antigens and a
      high throughput xTAG Luminex assay to simultaneously detect seven O-AGCs. Both
      methods accurately identified serotypes of 64 tested E. albertii strains. Our
      data revealed the high-level diversity of O-AGCs in E. albertii. We also provide
      valuable methods to reliably identify and serotype this bacterium.

PMID- 29018429
TI  - D-Ribose Interferes with Quorum Sensing to Inhibit Biofilm Formation of
      Lactobacillus paraplantarum L-ZS9.
AB  - Biofilms help bacteria survive under adverse conditions, and the quorum sensing
      (QS) system plays an important role in regulating their activities. Quorum
      sensing inhibitors (QSIs) have great potential to inhibit pathogenic biofilm
      formation and are considered possible replacements for antibiotics; however,
      further investigation is required to understand the mechanisms of action of QSIs
      and to avoid inhibitory effects on beneficial bacteria. Lactobacillus
      paraplantarum L-ZS9, isolated from fermented sausage, is a bacteriocin-producing
      bacteria that shows potential to be a probiotic starter. Since exogenous
      autoinducer-2 (AI-2) promoted biofilm formation of the strain, expression of
      genes involved in AI-2 production was determined in L. paraplantarum L-ZS9,
      especially the key gene luxS. D-Ribose was used to inhibit biofilm formation
      because of its AI-2 inhibitory activity. Twenty-seven differentially expressed
      proteins were identified by comparative proteomic analysis following D-ribose
      treatment and were functionally classified into six groups. Real-time
      quantitative PCR showed that AI-2 had a counteractive effect on transcription of
      the genes tuf, fba, gap, pgm, nfo, rib, and rpoN. Over-expression of the tuf,
      fba, gap, pgm, and rpoN genes promoted biofilm formation of L. paraplantarum L
      ZS9, while over-expression of the nfo and rib genes inhibited biofilm formation.
      In conclusion, D-ribose inhibited biofilm formation of L. paraplantarum L-ZS9 by
      regulating multiple genes involved in the glycolytic pathway, extracellular DNA
      degradation and transcription, and translation. This research provides a new
      mechanism of QSI regulation of biofilm formation of Lactobacillus and offers a
      valuable reference for QSI application in the future.

PMID- 29018430
TI  - Preliminary Transcriptome Analysis of Mature Biofilm and Planktonic Cells of
      Salmonella Enteritidis Exposure to Acid Stress.
AB  - Salmonella has emerged as a well-recognized food-borne pathogen, with many
      strains able to form biofilms and thus cause cross-contamination in food
      processing environments where acid-based disinfectants are widely encountered. In
      the present study, RNA sequencing was employed to establish complete
      transcriptome profiles of Salmonella Enteritidis in the forms of planktonic and
      biofilm-associated cells cultured in Tryptic Soytone Broth (TSB) and acidic TSB
      (aTSB). The gene expression patterns of S. Enteritidis significantly differed
      between biofilm-associated and planktonic cells cultivated under the same
      conditions. The assembled transcriptome of S. Enteritidis in this study contained
      5,442 assembled transcripts, including 3,877 differentially expressed genes
      (DEGs) identified in biofilm and planktonic cells. These DEGs were enriched in
      terms such as regulation of biological process, metabolic process, macromolecular
      complex, binding and transferase activity, which may play crucial roles in the
      biofilm formation of S. Enteritidis cultivated in aTSB. Three significant
      pathways were observed to be enriched under acidic conditions: bacterial
      chemotaxis, porphyrin-chlorophyll metabolism and sulfur metabolism. In addition,
      15 differentially expressed novel non-coding small RNAs (sRNAs) were identified,
      and only one was found to be up-regulated in mature biofilms. This preliminary
      study of the S. Enteritidis transcriptome serves as a basis for future
      investigations examining the complex network systems that regulate Salmonella
      biofilm in acidic environments, which provide information on biofilm formation
      and acid stress interaction that may facilitate the development of novel
      disinfection procedures in the food processing industry.

PMID- 29018431
TI  - Depression of Vaccinal Immunity to Marek's Disease by Infection with Chicken
      Infectious Anemia Virus.
AB  - Marek's disease (MD) has been occurring with increasing frequency in chickens in
      recent years. To our knowledge, however, there has been no report of the very
      virulent plus (vv+) MD virus (MDV) field isolate in China. Studies have shown
      that dual infection with immunosuppressive viruses such as chicken infectious
      anemia virus (CIAV) occurs frequently in chickens developing MD. In this study,
      we performed a designed set of in vivo experiments, which comprised five
      different groups of chickens, including the group of CVI988/Rispens-vaccinated
      chickens, the groups of CVI988/Rispens-vaccinated chickens infected with MDV or
      CIAV or both viruses (MDV and CIAV), and the group of MDV-challenged chickens.
      The effects of CIAV dual infection on the immunization of commercial MDV vaccine
      CVI988/Rispens were evaluated. The results show that infection of the SD15 strain
      of CIAV significantly reduced the weight and antibody titers to avian influenza
      virus (AIV)/Newcastle disease virus (NDV) inactivated vaccines of chickens
      immunized with the CVI988/Rispens, and resulted in the atrophy of thymus/bursa
      and the enlargement of spleen. The CVI988/Rispens vaccination conferred good
      immune protection for chickens challenged with 2000 PFU of the GX0101 strain of
      MDV. However, dual infection with SD15 significantly reduced the body weight,
      antibody titers induced by AIV/NDV inactivated vaccines and protective index of
      CVI988/Rispens, and resulted in the aggravation of the immunosuppression,
      mortality, and viremia of GX0101 in CVI988/Rispens-immunized/GX0101-challenged
      chickens. Overall, CIAV infection significantly reduced the protective effects of
      the CVI988/Rispens vaccine against MDV, implying that concurrent infection with
      CIAV may be a major contributor in the frequent attacks of MD in China in recent
      years.

PMID- 29018432
TI  - Maize Inoculation with Azospirillum brasilense Ab-V5 Cells Enriched with
      Exopolysaccharides and Polyhydroxybutyrate Results in High Productivity under Low
      N Fertilizer Input.
AB  - Although Azospirillum strains used in commercial inoculant formulations presents
      diazotrophic activity, it has been reported that their ability to produce
      phytohormones plays a pivotal role in plant growth-promotion, leading to a
      general recommendation of its use in association with regular N-fertilizer doses.
      In addition, a high variability in the effectiveness of Azospirillum inoculants
      is still reported under field conditions, contributing to the adoption of the
      inoculation technology as an additional management practice rather than its use
      as an alternative practice to the use of chemical inputs in agriculture. To
      investigate whether the content of stress-resistance biopolymers would improve
      the viability and performance of Azospirillum inoculants when used as substitute
      of N-fertilizers, biomass of A. brasilense strain Ab-V5 enriched in
      exopolysaccharides (EPS) and polyhydroxybutirate (PHB) was produced using a new
      culture medium developed by factorial mixture design, and the effectiveness of
      resulting inoculants was evaluated under field conditions. The culture medium
      formulation extended the log phase of A. brasilense cultures, which presented
      higher cell counts and increased EPS and PHB contents than observed in the
      cultures grown in the OAB medium used as control. An inoculation trial with maize
      conducted under greenhouse conditions and using the biopolymers-enriched Ab-V5
      cells demonstrated the importance of EPS and PHB to the long term bacterial
      viability in soil and to the effectiveness of inoculation. The effectiveness of
      liquid and peat inoculants prepared with Ab-V5 cells enriched with EPS and PHB
      was also evaluated under field conditions, using maize as target crop along
      different seasons, with the inoculants applied directly over seeds or at
      topdressing under limiting levels of N-fertilization. No additive effect on yield
      resulted from inoculation under high N fertilizer input, while inoculated plants
      grown under 80% reduction in N fertilizer showed yields at levels compared to
      fully fertilized plants, regardless the inoculation method. The presented data
      highlights the feasibility to partially substitute the N-fertilizer demand in non
      legume crops using high-quality inoculant formulations, prepared with
      diazotrophic bacteria enriched with stress-resistance biopolymers that confer
      increased viability an effectiveness to the bacterial cells.

PMID- 29018434
TI  - Commentary: Toxoplasma depends on lysosomal consumption of autophagosomes for
      persistent infection.

PMID- 29018433
TI  - Strain Identity of the Ectomycorrhizal Fungus Laccaria bicolor Is More Important
      than Richness in Regulating Plant and Fungal Performance under Nutrient Rich
      Conditions.
AB  - Effects of biodiversity on productivity are more likely to be expressed when
      there is greater potential for niche complementarity. In soil, chemically complex
      pools of nutrient resources should provide more opportunities for niche
      complementarity than chemically simple pools. Ectomycorrhizal (ECM) fungal
      genotypes can exhibit substantial variation in nutrient acquisition traits and
      are key components of soil biodiversity. Here, we tested the hypothesis that
      increasing the chemical complexity and forms of soil nutrients would enhance the
      effects of intraspecific ECM diversity on host plant and fungal productivity. In
      pure culture, we found substantial variation in growth of strains of the ECM
      fungus Laccaria bicolor on a range of inorganic and organic forms of nutrients.
      Subsequent experiments examined the effects of intraspecific identity and
      richness using Scots pine (Pinus sylvestris) seedlings colonized with different
      strains of L. bicolor growing on substrates supplemented with either inorganic or
      organic forms of nitrogen and phosphorus. Intraspecific identity effects on plant
      productivity were only found under the inorganic nutrient amendment, whereas
      intraspecific identity affected fungal productivity to a similar extent under
      both nutrient treatments. Overall, there were no significant effects of
      intraspecific richness on plant and fungal productivity. Our findings suggest
      soil nutrient composition does not interact strongly with ECM intraspecific
      richness, at least under experimental conditions where mineral nutrients were not
      limiting. Under these conditions, intraspecific identity of ECM fungi becomes
      more important than richness in modulating plant and fungal performance.

PMID- 29018436
TI  - Use of RNALater(r) Preservation for Virome Sequencing in Outbreak Settings.
AB  - Outbreaks of infectious diseases may occur in animal and human populations; this
      underlines the need for suitable One Health approaches. During outbreak
      situations, straightforward identification of etiological agents is indispensable
      for taking countermeasures. A recently published protocol for metagenomic virus
      detection in clinical specimens (TUViD-VM) was developed for snap-frozen tissues
      which can be challenging to obtain. Here, we describe the use of RNALater(r) 
      treated tissue at ambient temperatures for virome sequencing. This study
      demonstrates that samples stored in RNALater(r) buffer yield similar results to
      those stored snap-frozen.

PMID- 29018435
TI  - Lactobacillus plantarum BSGP201683 Isolated from Giant Panda Feces Attenuated
      Inflammation and Improved Gut Microflora in Mice Challenged with Enterotoxigenic
      Escherichia coli.
AB  - In this work, we searched for an effective probiotic that can help control
      intestinal infection, particularly enterotoxigenic Escherichia coli K88 (ETEC)
      invasion, in giant panda (Ailuropoda melanoleuca). As a potential probiotic
      strain, Lactobacillus plantarum BSGP201683 (L. plantarum G83) was isolated from
      the feces of giant panda and proven beneficial in vitro. This study was aimed to
      evaluate the protective effect of L. plantarum G83 in mice challenged with ETEC.
      The mice were orally administered with 0.2 mL of PBS containing L. plantarum G83
      at 0 colony-forming units (cfu) mL-1 (control; negative control, ETEC group), 5.0
      * 108 cfu mL-1 (LDLP), 5.0 * 109 cfu mL-1 (MDLP), and 5.0 * 1010 cfu mL-1 (HDLP)
      for 14 consecutive days. At day 15, the mice (LDLP, MDLP, HDLP, and ETEC groups)
      were challenged with ETEC and assessed at 0, 24, and 144 h. Animal health status;
      chemical and biological intestinal barriers; and body weight were measured.
      Results showed that L. plantarum G83 supplementation protected the mouse gut
      mainly by attenuating inflammation and improving the gut microflora. Most indices
      significantly changed at 24 h after challenge compared to those at 0 and 144 h.
      All treatment groups showed inhibited plasma diamine oxidase activity and D
      lactate concentration. Tight-junction protein expression was down-regulated, and
      interleukin (IL)-1beta, IL-6, IL-8, TLR4, and MyD88 levels were up-regulated in
      the jejunum in the LDLP and MDLP groups. The number of the Enterobacteriaceae
      family and the heat-labile enterotoxin (LT) gene decreased (P < 0.05) in the
      colons in the LDLP and MDLP groups. All data indicated that L. plantarum G83
      could attenuate acute intestinal inflammation caused by ETEC infection, and the
      low and intermediate doses were superior to the high dose. These findings
      suggested that L. plantarum G83 may serve as a protective probiotic for
      intestinal disease and merits further investigation.

PMID- 29018438
TI  - Antibody Immunity Induced by H7N9 Avian Influenza Vaccines: Evaluation Criteria,
      Affecting Factors, and Implications for Rational Vaccine Design.
AB  - Severe H7N9 avian influenza virus (AIV) infections in humans have public health
      authorities around the world on high alert for the potential development of a
      human influenza pandemic. Currently, the newly-emerged highly pathogenic avian
      influenza A (H7N9) virus poses a dual challenge for public health and poultry
      industry. Numerous H7N9 vaccine candidates have been generated using various
      platforms. Immunization trials in animals and humans showed that H7N9 vaccines
      are apparently poorly immunogenic because they induced low hemagglutination
      inhibition and virus neutralizing antibody titers. However, H7N9 vaccines elicit
      comparable levels of total hemagglutinin (HA)-reactive IgG antibody as the
      seasonal influenza vaccines, suggesting H7N9 vaccines are as immunogenic as their
      seasonal counterparts. A large fraction of overall IgG antibody is non
      neutralizing antibody and they target unrecognized epitopes outside of the
      traditional antigenic sites in HA. Further, the Treg epitope identified in H7 HA
      may at least partially contribute to regulation of antibody immunity. Here, we
      review the latest advances for the development of H7N9 vaccines and discuss the
      influence of serological criteria on evaluation of immunogenicity of H7N9
      vaccines. Next, we discuss factors affecting antibody immunity induced by H7N9
      vaccines, including the change in antigenic epitopes in HA and the presence of
      the Treg epitope. Last, we present our perspectives for the unique features of
      antibody immunity of H7N9 vaccines and propose some future directions to improve
      or modify antibody response induced by H7N9 vaccines. This perspective would
      provide critical implications for rational design of H7N9 vaccines for human and
      veterinary use.

PMID- 29018439
TI  - Neutrophils from Patients with Primary Ciliary Dyskinesia Display Reduced
      Chemotaxis to CXCR2 Ligands.
AB  - Primary ciliary dyskinesia (PCD), cystic fibrosis (CF), and chronic obstructive
      airway disease are characterized by neutrophilic inflammation in the lungs. In CF
      and chronic obstructive airway disease, improper functioning of neutrophils has
      been demonstrated. We hypothesized that the pulmonary damage in PCD might be
      aggravated by abnormal functioning neutrophils either as a primary consequence of
      the PCD mutation or secondary to chronic inflammation. We analyzed chemotactic
      responses and chemoattractant receptor expression profiles of peripheral blood
      neutrophils from 36 patients with PCD, 21 healthy children and 19 healthy adults.
      We stimulated peripheral blood monocytes from patients and healthy controls and
      measured CXCL8 and IL-1beta production with ELISA. PCD neutrophils displayed
      reduced migration toward CXCR2 ligands (CXCL5 and CXCL8) in the shape change,
      microchamber and microslide chemotaxis assays, whereas leukotriene B4 and
      complement component 5a chemotactic responses were not significantly different.
      The reduced response to CXCL8 was observed in all subgroups of patients with PCD
      (displaying either normal ultrastructure, dynein abnormalities or central pair
      deficiencies) and correlated with lung function. CXCR2 was downregulated in about
      65% of the PCD patients, suggestive for additional mechanisms causing CXCR2
      impairment. After treatment with the TLR ligands lipopolysaccharide and
      peptidoglycan, PCD monocytes produced more CXCL8 and IL-1beta compared to
      controls. Moreover, PCD monocytes also responded stronger to IL-1beta stimulation
      in terms of CXCL8 production. In conclusion, we revealed a potential link between
      CXCR2 and its ligand CXCL8 and the pathogenesis of PCD.

PMID- 29018437
TI  - Biocontrol of Bacterial Leaf Blight of Rice and Profiling of Secondary
      Metabolites Produced by Rhizospheric Pseudomonas aeruginosa BRp3.
AB  - Xanthomonas oryzae pv. oryzae (Xoo) is widely prevalent and causes Bacterial Leaf
      Blight (BLB) in Basmati rice grown in different areas of Pakistan. There is a
      need to use environmentally safe approaches to overcome the loss of grain yield
      in rice due to this disease. The present study aimed to develop inocula, based on
      native antagonistic bacteria for biocontrol of BLB and to increase the yield of
      Super Basmati rice variety. Out of 512 bacteria isolated from the rice
      rhizosphere and screened for plant growth promoting determinants, the isolate
      BRp3 was found to be the best as it solubilized 97 MUg/ mL phosphorus, produced
      30 MUg/mL phytohormone indole acetic acid and 15 mg/ L siderophores in vitro. The
      isolate BRp3 was found to be a Pseudomonas aeruginosa based on 16S rRNA gene
      sequencing (accession no. HQ840693). This bacterium showed antagonism in vitro
      against different phytopathogens including Xoo and Fusarium spp. Strain BRp3
      showed consistent pathogen suppression of different strains of BLB pathogen in
      rice. Mass spectrometric analysis detected the production of siderophores (1
      hydroxy-phenazine, pyocyanin, and pyochellin), rhamnolipids and a series of
      already characterized 4-hydroxy-2-alkylquinolines (HAQs) as well as novel 2,3,4
      trihydroxy-2-alkylquinolines and 1,2,3,4-tetrahydroxy-2-alkylquinolines in crude
      extract of BRp3. These secondary metabolites might be responsible for the
      profound antibacterial activity of BRp3 against Xoo pathogen. Another
      contributing factor toward the suppression of the pathogen was the induction of
      defense related enzymes in the rice plant by the inoculated strain BRp3. When
      used as an inoculant in a field trial, this strain enhanced the grain and straw
      yields by 51 and 55%, respectively, over non-inoculated control. Confocal Laser
      Scanning Microscopy (CLSM) used in combination with immunofluorescence marker
      confirmed P. aeruginosa BRp3 in the rice rhizosphere under sterilized as well as
      field conditions. The results provide evidence that novel secondary metabolites
      produced by BRp3 may contribute to its activity as a biological control agent
      against Xoo and its potential to promote the growth and yield of Super Basmati
      rice.

PMID- 29018440
TI  - Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity.
AB  - OBJECTIVE: Roseburia hominis is a flagellated gut anaerobic bacterium belonging
      to the Lachnospiraceae family within the Firmicutes phylum. A significant
      decrease of R. hominis colonization in the gut of ulcerative colitis patients has
      recently been demonstrated. In this work, we have investigated the mechanisms of
      R. hominis-host cross talk using both murine and in vitro models. DESIGN: The
      complete genome sequence of R. hominis A2-183 was determined. C3H/HeN germ-free
      mice were mono-colonized with R. hominis, and the host-microbe interaction was
      studied using histology, transcriptome analyses and FACS. Further investigations
      were performed in vitro and using the TLR5KO and DSS-colitis murine models.
      RESULTS: In the bacterium, R. hominis, host gut colonization upregulated genes
      involved in conjugation/mobilization, metabolism, motility, and chemotaxis. In
      the host cells, bacterial colonization upregulated genes related to antimicrobial
      peptides, gut barrier function, toll-like receptors (TLR) signaling, and T cell
      biology. CD4+CD25+FoxP3+ T cell numbers increased in the lamina propria of both
      mono-associated and conventional mice treated with R. hominis. Treatment with the
      R. hominis bacterium provided protection against DSS-induced colitis. The role of
      flagellin in host-bacterium interaction was also investigated. CONCLUSION: Mono
      association of mice with R. hominis bacteria results in specific bidirectional
      gene expression patterns. A set of genes thought to be important for host
      colonization are induced in R. hominis, while the host cells respond by
      strengthening gut barrier function and enhancing Treg population expansion,
      possibly via TLR5-flagellin signaling. Our data reveal the immunomodulatory
      properties of R. hominis that could be useful for the control and treatment of
      gut inflammation.

PMID- 29018441
TI  - Very Early-Onset Inflammatory Manifestations of X-Linked Chronic Granulomatous
      Disease.
AB  - Chronic granulomatous disease (CGD) is a rare primary immune deficiency caused by
      mutations in genes coding for components of the nicotinamide adenine dinucleotide
      phosphate oxidase, characterized by severe and recurrent bacterial and fungal
      infections, together with inflammatory complications. Dysregulation of
      inflammatory responses are often present in this disease and may lead to
      granulomatous lesions, most often affecting the gastrointestinal (GI) and urinary
      tracts. Treatment of inflammatory complications usually includes corticosteroids,
      whereas antimicrobial prophylaxis is used for infection prevention. Curative
      treatment of both infectious susceptibility and inflammatory disease can be
      achieved by hematopoietic stem cell transplantation. We report herein three
      patients with the same mutation of the CYBB gene who presented with very early
      onset and severe GI manifestations of X-linked CGD. The most severely affected
      patient had evidence of antenatal inflammatory involvement of the GI and urinary
      tracts. Extreme hyperleukocytosis with eosinophilia and high inflammatory markers
      were observed in all three patients. A Mycobacterium avium lung infection and an
      unidentified fungal lung infection occurred in two patients both during their
      first year of life, which is indicative of the severity of the disease. All three
      patients underwent bone marrow transplantation and recovered fully from their
      initial symptoms. To our knowledge, these are the first reports of patients with
      such an early-onset and severe inflammatory manifestations of CGD.

PMID- 29018442
TI  - Lower Expression of MicroRNA-155 Contributes to Dysfunction of Natural Killer
      Cells in Patients with Chronic Hepatitis B.
AB  - MicroRNAs have been reported to be regulated in different ways in a variety of
      liver diseases. As a key modulator of cellular function in both innate and
      adaptive immunity, the role of miR-155 in chronic hepatitis B virus infection
      remains largely unknown. Here, we investigated the expression and function of miR
      155 in chronic hepatitis B (CHB) patients. It was found that miR-155 expression
      in peripheral blood mononuclear cells (PBMCs) was lower in CHB patients than
      healthy controls (HC). Among CHB infection, immune-active (IA) patients with
      abnormal alanine aminotransferase (ALT) levels had relatively higher miR-155
      expression in PBMCs and serum than immune-tolerant carriers, but were comparable
      to inactive carriers. Moreover, there was a positive correlation between miR-155
      expression and ALT levels in CHB patients. Particularly, miR-155 expression in
      natural killer (NK) cells was significantly downregulated in IA patients compared
      with HC. Inversely, suppressor of cytokine signaling 1 (SOCS1), a target of miR
      155, was upregulated in NK cells of IA patients. Overexpression of miR-155 in NK
      cells from IA patients led to a decrease in SOCS1 expression and an increase of
      IFN-gamma production. Finally, accompanied by the normalization of ALT, miR-155
      expression in PBMCs gradually decreased during telbivudine or peg-IFN-alpha-2a
      therapy. Interestingly, higher miR-155 expression at baseline was associated with
      better response to telbivudine therapy, but not peg-IFN-alpha-2a. In conclusion,
      our data suggested that miR-155 downregulation in NK cells of IA patients
      impaired IFN-gamma production by targeting SOCS1, which may contribute to immune
      dysfunction during CHB infection. Additionally, baseline miR-155 expression could
      predict the treatment response to telbivudine therapy.

PMID- 29018443
TI  - Extracellular Vesicles Arising from Apoptotic Cells in Tumors: Roles in Cancer
      Pathogenesis and Potential Clinical Applications.
AB  - It is known that apoptotic cells can have diverse effects on the tumor
      microenvironment. Emerging evidence indicates that, despite its renowned role in
      tumor suppression, apoptosis may also promote oncogenic evolution or
      posttherapeutic relapse through multiple mechanisms. These include
      immunomodulatory, anti-inflammatory, and trophic environmental responses to
      apoptosis, which drive tumor progression. Our group has introduced the term "onco
      regenerative niche (ORN)" to describe a conceptual network of conserved cell
      death-driven tissue repair and regeneration mechanisms that are hijacked in
      cancer. We propose that, among the key elements of the ORN are extracellular
      vesicles (EVs), notably those derived from apoptotic tumor cells. EVs are
      membrane-delimited subcellular particles, which contain multiple classes of
      bioactive molecules including markers of the cell from which they are derived.
      EVs are implicated in an increasing number of physiological and pathological
      contexts as mediators of local and systemic intercellular communication and
      detection of specific EVs may be useful in monitoring disease progression. Here,
      we discuss the mechanisms by which EVs produced by apoptotic tumor cells-both
      constitutively and as a consequence of therapy-may mediate host responsiveness to
      cell death in cancer. We also consider how the monitoring of such EVs and their
      cargoes may in the future help to improve cancer diagnosis, staging, and
      therapeutic efficacy.

PMID- 29018444
TI  - Mucosa-Associated Lymphoid Tissue Lymphoma Translocation Protein 1 Positively
      Modulates Matrix Metalloproteinase-9 Production in Alveolar Macrophages upon Toll
      Like Receptor 7 Signaling and Influenza Virus Infection.
AB  - Influenza A virus (IAV) infection causes significant morbidity and mortality
      worldwide. Matrix metalloproteinase-9 (MMP-9) degrades extracellular matrix and
      is involved in the pathology of influenza. It has been reported that MMP-9
      mediates neutrophil migration in IAV infection. Whether alveolar macrophages, the
      first immune cells that encounter IAV, produce MMP-9, and the mechanism of its
      regulation have never been investigated. As Toll-like receptor 7 (TLR7) is one of
      the receptors in innate immune cells that recognize IAV, we used TLR7 agonists
      and IAV to stimulate alveolar macrophage MH-S cells, primary macrophages, and
      bone marrow neutrophils. Results showed that MMP-9 expression in macrophages is
      inducible by TLR7 agonists and IAV, yet, MMP-9 production by neutrophils is not
      inducible by either one of them. We hypothesized that MMP-9 production in
      macrophages is mediated through TLR7-NF-kappaB pathway and used microarray to
      analyze TLR7 agonist-induced NF-kappaB-related genes. Mucosa-associated lymphoid
      tissue lymphoma translocation protein 1 (MALT1), a positive regulator of NF
      kappaB, is amongst the top highly induced genes. By use of MALT1 inhibitor (z
      VRPR-fmk) and alveolar macrophages from MALT1-deficient mice, we found that MMP-9
      production is MALT1-dependent. While MALT1 can act as a paracaspase in
      lymphocytes through degrading various signaling proteins, we discovered that
      MALT1 functions to reduce a negative regulator of NF-kappaB, cylindromatosis
      (CYLD), in alveolar macrophages. IAV-induced MMP-9, TNF, and IL-6 in lungs of
      MALT1-deficient mice are significantly lower than in wild-type mice after
      intratracheal infection. MALT1-deficient mice also have less body weight loss and
      longer survival after infection. Taken together, we demonstrated a novel role of
      MALT1 in regulating alveolar macrophage MMP-9 production whose presence
      exacerbates the severity of influenza.

PMID- 29018446
TI  - Autophagy Proteins in Phagocyte Endocytosis and Exocytosis.
AB  - Autophagy was initially described as a catabolic pathway that recycles nutrients
      of cytoplasmic constituents after lysosomal degradation during starvation. Since
      the immune system monitors products of lysosomal degradation via major
      histocompatibility complex (MHC) class II restricted antigen presentation,
      autophagy was found to process intracellular antigens for display on MHC class II
      molecules. In recent years, however, it has become apparent that the molecular
      machinery of autophagy serves phagocytes in many more membrane trafficking
      pathways, thereby regulating immunity to infectious disease agents. In this
      minireview, we will summarize the recent evidence that autophagy proteins
      regulate phagocyte endocytosis and exocytosis for myeloid cell activation,
      pathogen replication, and MHC class I and II restricted antigen presentation.
      Selective stimulation and inhibition of the respective functional modules of the
      autophagy machinery might constitute valid therapeutic options in the discussed
      disease settings.

PMID- 29018448
TI  - IFN-gamma-STAT1-iNOS Induces Myeloid Progenitors to Acquire Immunosuppressive
      Activity.
AB  - Autoimmune diseases often induce dysregulated hematopoiesis with altered number
      and function of hematopoietic stem and progenitor cells (HSPCs). However, there
      are limited studies on the direct regulation of HSPCs on T cells, which are often
      detrimental to autoimmunity. Here, we found that in a murine model of
      Concanavalin A-induced autoimmune hepatitis, LSK (Lineage-Sca-1+c-Kit+)-like
      cells accumulated in liver, spleen, and bone marrow (BM), which were myeloid
      progenitors (Lineage-Sca-1-c-Kit+) that upregulated Sca-1 expression upon T cell
      derived IFN-gamma stimulation. Strikingly, BM LSK-like cells from mice induced by
      Con A to develop autoimmune hepatitis or alternatively myeloid progenitors from
      wild-type mice possessed strong in vitro suppressive ability. Their suppressive
      function depended on T cell-derived IFN-gamma in a paracrine fashion, which
      induced STAT1 phosphorylation, inducible nitric oxide synthase expression, and
      nitric oxide production. Blocking IFN-gamma/IFN-gamma receptor interaction,
      knockout of STAT1, or iNOS inhibition abrogated their suppressive function. In
      addition, the suppressive function was independent of differentiation; mitomycin
      C-treated myeloid progenitors maintained T cell suppressive ability in vitro. Our
      data demonstrate a mechanism of inflammation induced suppressive function of
      myeloid progenitors, which may participate directly in suppressing T cell
      mediated immunopathology.

PMID- 29018445
TI  - Natural Killer T Cells in Cancer Immunotherapy.
AB  - Natural killer T (NKT) cells are specialized CD1d-restricted T cells that
      recognize lipid antigens. Following stimulation, NKT cells lead to downstream
      activation of both innate and adaptive immune cells in the tumor
      microenvironment. This has impelled the development of NKT cell-targeted
      immunotherapies for treating cancer. In this review, we provide a brief overview
      of the stimulatory and regulatory functions of NKT cells in tumor immunity as
      well as highlight preclinical and clinical studies based on NKT cells. Finally,
      we discuss future perspectives to better harness the potential of NKT cells for
      cancer therapy.

PMID- 29018449
TI  - Mechanisms, Cofactors, and Augmenting Factors Involved in Anaphylaxis.
AB  - Anaphylaxis is an acute and life-threatening systemic reaction. Many triggers
      have been described, including food, drug, and hymenoptera allergens, which are
      the most frequently involved. The mechanisms described in anaphylactic reactions
      are complex and implicate a diversity of pathways. Some of these mechanisms may
      be key to the development of the anaphylactic reaction, while others may only
      modify its severity. Although specific IgE, mast cells, and basophils are
      considered the principal players in anaphylaxis, alternative mechanisms have been
      proposed in non-IgE anaphylactic reactions. Neutrophils, macrophages, as well as
      basophils, have been involved, as have IgG-dependent, complement and contact
      system activation. A range of cationic substances can induce antibody-independent
      mast cells activation through MRGPRX2 receptor. Cofactors and augmenting factors
      may explain why, in some patients, food allergen exposure can cause anaphylaxis,
      while in other clinical scenario it can be tolerated or elicits a mild reaction.
      With the influence of these factors, food allergic reactions may be induced at
      lower doses of allergen and/or become more severe. Exercise, alcohol, estrogens,
      and some drugs such as Non-steroidal anti-inflammatory drugs, angiotensin
      converting enzyme inhibitors, beta-blockers, and lipid-lowering drugs are the
      main factors described, though their mechanisms and signaling pathways are poorly
      understood.

PMID- 29018451
TI  - In the Wnt of Paneth Cells: Immune-Epithelial Crosstalk in Small Intestinal
      Crohn's Disease.
AB  - Paneth cells, specialized secretory epithelial cells of the small intestine, play
      a pivotal role in host defense and regulation of microbiota by producing
      antimicrobial peptides especially-but not only-the human alpha-defensin 5 (HD5)
      and HD6. In small intestinal Crohn's disease (CD) which is an entity of
      inflammatory bowel diseases, the expression of HD5 and HD6 is specifically
      compromised leading to a disturbed barrier and change in the microbial community.
      Different genetically driven but also non-genetic defects associated with small
      intestinal CD affect different lines of antimicrobial Paneth cell functions. In
      this review, we focus on the mechanisms and the crosstalk of Paneth cells and
      bone marrow-derived cells and highlight recent studies about the role of the Wnt
      signaling pathway in this connection of ileal CD. In summary, different lines of
      investigations led by us but also now numerous other groups support and reconfirm
      the proposed classification of this disease entity as Paneth's disease.

PMID- 29018450
TI  - Exploring the Immunopathogenesis of Viral Hemorrhagic Fever in Mice with a
      Humanized Immune System.
AB  - Viral hemorrhagic fever (VHF) as a disease entity was first codified in the 1930s
      by soviet scientists investigating patients suffering from hantavirus infection.
      The group of hemorrhagic fever viruses (HFVs) has since expanded to include
      members from at least four different virus families: Arenaviridae, Bunyaviridae,
      Filoviridae, and Flaviviridae, all enveloped single-stranded RNA viruses. After
      infection, the natural hosts of HFVs do not develop symptoms, whereas humans can
      be severely affected. This observation and other evidence from experimental data
      suggest that the human immune system plays a crucial role in VHF pathogenesis.
      For this reason mice with a human immune system, referred to here as humanized
      mice (humice), are valuable tools that provide insight into disease mechanisms
      and allow for preclinical testing of novel vaccinations approaches as well as
      antiviral agents. In this article, we review the impact of humice in VHF
      research.

PMID- 29018447
TI  - TRIM25 in the Regulation of the Antiviral Innate Immunity.
AB  - TRIM25 is an E3 ubiquitin ligase enzyme that is involved in various cellular
      processes, including regulation of the innate immune response against viruses.
      TRIM25-mediated ubiquitination of the cytosolic pattern recognition receptor RIG
      I is an essential step for initiation of the intracellular antiviral response and
      has been thoroughly documented. In recent years, however, additional roles of
      TRIM25 in early innate immunity are emerging, including negative regulation of
      RIG-I, activation of the melanoma differentiation-associated protein 5
      mitochondrial antiviral signaling protein-TRAF6 antiviral axis and modulation of
      p53 levels and activity. In addition, the ability of TRIM25 to bind RNA may
      uncover new mechanisms by which this molecule regulates intracellular signaling
      and/or RNA virus replication.

PMID- 29018452
TI  - Kv1.3 Channel Blockade Modulates the Effector Function of B Cells in
      Granulomatosis with Polyangiitis.
AB  - B cells are central to the pathogenesis of granulomatosis with polyangiitis
      (GPA), exhibiting both (auto)antibody-dependent and -independent properties.
      Class-switched memory B cells in particular are a major source of pathogenic
      autoantibodies. These cells are characterized by high expression levels of Kv1.3
      potassium channels, which may offer therapeutic potential for Kv1.3 blockade. In
      this study, we investigated the effect of the highly potent Kv1.3 blocker ShK-186
      on B cell properties in GPA in vitro. Circulating B cell subsets were determined
      from 33 GPA patients and 17 healthy controls (HCs). Peripheral blood mononuclear
      cells (PBMCs) from GPA patients, and HCs were stimulated in vitro in the presence
      and absence of ShK-186. The production of total and antineutrophil cytoplasmic
      antibodies targeting proteinase 3 (PR3-ANCA) IgG was analyzed by enzyme-linked
      immunosorbent assay and Phadia EliA, respectively. In addition, effects of ShK
      186 on B cell proliferation and cytokine production were determined by flow
      cytometry. The frequency of circulating switched and unswitched memory B cells
      was decreased in GPA patients as compared to HC. ShK-186 suppressed the
      production of both total and PR3-ANCA IgG in stimulated PBMCs. A strong decrease
      in production of tumor necrosis factor alpha (TNFalpha), interleukin (IL)-2, and
      interferon gamma was observed upon ShK-186 treatment, while effects on IL-10
      production were less pronounced. As such, ShK-186 modulated the TNFalpha/IL-10
      ratio among B cells, resulting in a relative increase in the regulatory B cell
      pool. ShK-186 modulates the effector functions of B cells in vitro by decreasing
      autoantibody and pro-inflammatory cytokine production. Kv1.3 channel blockade may
      hold promise as a novel therapeutic strategy in GPA and other B cell-mediated
      autoimmune disorders.

PMID- 29018454
TI  - Corrigendum: Functional and Structural Characterization of a Novel HLA-DRB1*04:01
      Restricted alpha-Enolase T Cell Epitope in Rheumatoid Arthritis.
AB  - [This corrects the article on p. 494 in vol. 7, PMID: 27895642.].

PMID- 29018453
TI  - Inulin-Type Fructans Modulates Pancreatic-Gut Innate Immune Responses and Gut
      Barrier Integrity during Experimental Acute Pancreatitis in a Chain Length
      Dependent Manner.
AB  - Acute pancreatitis (AP) is a common abdominal inflammatory disorder and one of
      the leading causes of hospital admission for gastrointestinal disorders. No
      specific pharmacological or nutritional therapy is available but highly needed.
      Inulin-type fructans (ITFs) are capable of modifying gut immune and barrier
      homeostasis in a chemistry-dependent manner and hence potentially applicable for
      managing AP, but their efficacy in AP has not been demonstrated yet. The current
      study aimed to examine and compare modulatory effects of ITFs with different
      degrees of fermentability on pancreatic-gut immunity and barrier function during
      experimentally induced AP in mice. BALB/c mice were fed short (I)- or long (IV)
      chain ITFs supplemented diets for up to 3 days before AP induction by caerulein.
      Attenuating effects on AP development were stronger with ITF IV than with ITF I.
      We found that long-chain ITF IV attenuated the severity of AP, as evidenced by
      reduced serum amylase levels, lipase levels, pancreatic myeloperoxidase activity,
      pancreatic edema, and histological examination demonstrating reduced pancreatic
      damage. Short-chain ITF I demonstrated only partial protective effects. Both ITF
      IV and ITF I modulated AP-associated systemic cytokine levels. ITF IV but not ITF
      I restored AP-associated intestinal barrier dysfunction by upregulating colonic
      tight junction modulatory proteins, antimicrobial peptides, and improved general
      colonic histology. Additionally, differential modulatory effects of ITF IV and
      ITF I were observed on pancreatic and gut immunity: ITF IV supplementation
      prevented innate immune cell infiltration in the pancreas and colon and tissue
      cytokine production. Similar effects were only observed in the gut with ITF I and
      not in the pancreas. Lastly, ITF IV but not ITF I downregulated AP-triggered
      upregulation of IL-1 receptor-associated kinase 4 (IRAK-4) and phosphor-c-Jun N
      terminal kinase (p-JNK), and a net decrease of phosphor-nuclear factor kappa
      light-chain-enhancer of activated B cells (NF-kappaB) p65 (p-NF-kappaB p65)
      nuclear translocation and activation in the pancreas. Our findings demonstrate a
      clear chain length-dependent effect of inulin on AP. The attenuating effects are
      caused by modulating effects of long-chain inulin on the pancreatic-gut immunity
      via the pancreatic IRAK-4/p-JNK/p-NF-kappaBp65 signaling pathway and on
      prevention of disruption of the gut barrier.

PMID- 29018455
TI  - Seed Nutrition and Quality, Seed Coat Boron and Lignin Are Influenced by Delayed
      Harvest in Exotically-Derived Soybean Breeding Lines under High Heat.
AB  - The timing of harvest is a major factor affecting seed quality in soybean,
      particularly in Midsouthern USA, when rain during harvest period is not uncommon.
      The objective of this research was to evaluate the effects of time of harvest on
      soybean seed quality (seed composition, germination, seed coat boron, and lignin)
      in high germinability (HG) breeding lines (50% exotic) developed under high heat.
      The hypothesis was that seeds of HG lines possess physiological and genetic
      traits for a better seed quality at harvest maturity and delayed harvest. A 2
      year field experiment was conducted under irrigated conditions. Results showed
      that, at harvest maturity, the exotic HG lines had higher seed protein, oleic
      acid, sugars, seed coat boron, and seed coat lignin, but lower seed oil compared
      with the non-exotic checks (Control), confirming our hypothesis. At 28 days after
      harvest maturity (delayed harvest), the content of seed protein, oleic acid,
      sugars, seed coat boron, and seed coat lignin were higher in some of the HG lines
      compared with the checks, indicating a possible involvement of these seed
      constituents, especially seed coat boron and seed coat lignin, in maintaining
      seed coat integrity and protecting seed coat against physical damage. Highly
      significant positive correlations were found between germination and seed
      protein, oleic acid, sugars, and seed coat boron and seed coat lignin. Highly
      significant negative correlation was found between germination and oil, linoleic
      acid, seed coat wrinkling, shattering, and hard seed. Yields of some HG lines
      were competitive with checks. This research demonstrated that time of harvesting
      is an important factor influencing seed protein and oil production. Also, since
      high oleic acid is desirable for oxidative stability, shelf-life and biodiesel
      properties, using HG lines could positively influence these important traits.
      This result should suggest to breeders of some of the advantages of selecting for
      high seed coat boron and lignin, and inform growers of the importance of timely
      harvest for maintaining high seed quality.

PMID- 29018456
TI  - Virtual Plants Need Water Too: Functional-Structural Root System Models in the
      Context of Drought Tolerance Breeding.
AB  - Developing a sustainable agricultural model is one of the great challenges of the
      coming years. The agricultural practices inherited from the Green Revolution of
      the 1960s show their limits today, and new paradigms need to be explored to
      counter rising issues such as the multiplication of climate-change related
      drought episodes. Two such new paradigms are the use of functional-structural
      plant models to complement and rationalize breeding approaches and a renewed
      focus on root systems as untapped sources of plant amelioration. Since the late
      1980s, numerous functional and structural models of root systems were developed
      and used to investigate the properties of root systems in soil or lab-conditions.
      In this review, we focus on the conception and use of such root models in the
      broader context of research on root-driven drought tolerance, on the basis of
      root system architecture (RSA) phenotyping. Such models result from the
      integration of architectural, physiological and environmental data. Here, we
      consider the different phenotyping techniques allowing for root architectural and
      physiological study and their limits. We discuss how QTL and breeding studies
      support the manipulation of RSA as a way to improve drought resistance. We then
      go over the integration of the generated data within architectural models, how
      those architectural models can be coupled with functional hydraulic models, and
      how functional parameters can be measured to feed those models. We then consider
      the assessment and validation of those hydraulic models through confrontation of
      simulations to experimentations. Finally, we discuss the up and coming challenges
      facing root systems functional-structural modeling approaches in the context of
      breeding.

PMID- 29018457
TI  - Pre-infestation of Tomato Plants by Aphids Modulates Transmission-Acquisition
      Relationship among Whiteflies, Tomato Yellow Leaf Curl Virus (TYLCV) and Plants.
AB  - Herbivory defense systems in plants are largely regulated by jasmonate-(JA) and
      salicylate-(SA) signaling pathways. Such defense mechanisms may impact insect
      feeding dynamic, may also affect the transmission-acquisition relationship among
      virus, plants and vectoring insects. In the context of the tomato - whitefly -
      Tomato Yellow Leaf Curl Virus (TYLCV) biological model, we tested the impact of
      pre-infesting plants with a non-vector insect (aphid Myzus persicae) on feeding
      dynamics of a vector insect (whitefly Bemisia tabaci) as well as virus
      transmission-acquisition. We showed that an aphid herbivory period of 0-48 h led
      to a transient systemic increase of virus concentration in the host plant (root,
      stem, and leaf), with the same pattern observed in whiteflies feeding on aphid
      infested plants. We used real-time quantitative PCR to study the expression of
      key genes of the SA- and JA-signaling pathways, as well as electrical penetration
      graph (EPG) to characterize the impact of aphid pre-infestation on whitefly
      feeding during TYLCV transmission (whitefly to tomato) and acquisition (tomato to
      whitefly). The impact of the duration of aphid pre-infestation (0, 24, or 48 h)
      on phloem feeding by whitefly (E2) during the transmission phase was similar to
      that of global whitefly feeding behavior (E1, E2 and probing duration) during the
      acquisition phase. In addition, we observed that a longer phase of aphid pre
      infestation prior to virus transmission by whitefly led to the up-regulation and
      down-regulation of SA- and JA-signaling pathway genes, respectively. These
      results demonstrated a significant impact of aphid pre-infestation on the tomato 
      whitefly - TYLCV system. Transmission and acquisition of TYLCV was positively
      correlated with feeding activity of B. tabaci, and both were mediated by the SA-
      and JA-pathways. TYLCV concentration during the transmission phases was modulated
      by up- and down-regulation of SA- and JA-pathways, respectively. The two pathways
      were inconsistent during the acquisition phase; SA- related genes were up
      regulated, whereas those up- and down-stream of the JA pathway showed a more
      complex relationship. These findings enhance our understanding of plant -
      herbivore - virus interactions, which are potentially important for development
      of ecologically sound pest and pathogen management programs.

PMID- 29018458
TI  - Genome-Wide Association Study of Major Agronomic Traits Related to Domestication
      in Peanut.
AB  - Peanut (Arachis hypogaea) consists of two subspecies, hypogaea and fastigiata,
      and has been cultivated worldwide for hundreds of years. Here, 158 peanut
      accessions were selected to dissect the molecular footprint of agronomic traits
      related to domestication using specific-locus amplified fragment sequencing (SLAF
      seq method). Then, a total of 17,338 high-quality single nucleotide polymorphisms
      (SNPs) in the whole peanut genome were revealed. Eleven agronomic traits in 158
      peanut accessions were subsequently analyzed using genome-wide association
      studies (GWAS). Candidate genes responsible for corresponding traits were then
      analyzed in genomic regions surrounding the peak SNPs, and 1,429 genes were found
      within 200 kb windows centerd on GWAS-identified peak SNPs related to
      domestication. Highly differentiated genomic regions were observed between
      hypogaea and fastigiata accessions using FST values and sequence diversity (pi)
      ratios. Among the 1,429 genes, 662 were located on chromosome A3, suggesting the
      presence of major selective sweeps caused by artificial selection during long
      domestication. These findings provide a promising insight into the complicated
      genetic architecture of domestication-related traits in peanut, and reveal whole
      genome SNP markers of beneficial candidate genes for marker-assisted selection
      (MAS) in future breeding programs.

PMID- 29018459
TI  - Sequencing of Single Pollen Nuclei Reveals Meiotic Recombination Events at
      Megabase Resolution and Circumvents Segregation Distortion Caused by Postmeiotic
      Processes.
AB  - Meiotic recombination is a fundamental mechanism to generate novel allelic
      combinations which can be harnessed by breeders to achieve crop improvement. The
      recombination landscape of many crop species, including the major crop barley, is
      characterized by a dearth of recombination in 65% of the genome. In addition,
      segregation distortion caused by selection on genetically linked loci is a
      frequent and undesirable phenomenon in double haploid populations which hampers
      genetic mapping and breeding. Here, we present an approach to directly
      investigate recombination at the DNA sequence level by combining flow-sorting of
      haploid pollen nuclei of barley with single-cell genome sequencing. We confirm
      the skewed distribution of recombination events toward distal chromosomal regions
      at megabase resolution and show that segregation distortion is almost absent if
      directly measured in pollen. Furthermore, we show a bimodal distribution of inter
      crossover distances, which supports the existence of two classes of crossovers
      which are sensitive or less sensitive to physical interference. We conclude that
      single pollen nuclei sequencing is an approach capable of revealing recombination
      patterns in the absence of segregation distortion.

PMID- 29018460
TI  - The First Genetic Map in Sweet Osmanthus (Osmanthus fragrans Lour.) Using
      Specific Locus Amplified Fragment Sequencing.
AB  - Osmanthus fragrans is an ornamental plant of substantial commercial value, and no
      genetic linkage maps of this species have previously been reported. Specific
      locus amplified fragment sequencing (SLAF-seq) is a recently developed technology
      that allows massive single nucleotide polymorphisms (SNPs) to be identified and
      high-resolution genotyping. In our current research, we generated the first
      genetic map of O. fragrans using SLAF-seq, which is composed with 206.92 M paired
      end reads and 173,537 SLAF markers. Among total 90,715 polymorphic SLAF markers,
      15,317 polymorphic SLAFs could be used for genetic map construction. The
      integrated map contained 14,189 high quality SLAFs that were grouped in 23
      genetic linkage groups, with a total length of 2962.46 cM and an average distance
      of 0.21 cM between two adjacent markers. In addition, 23,664 SNPs were identified
      from the mapped markers. As far as we know, this is the first of the genetic map
      of O. fragrans. Our results are further demonstrate that SLAF-seq is a very
      effective method for developing markers and constructing high-density linkage
      maps. The SNP markers and the genetic map reported in this study should be
      valuable resource in future research.

PMID- 29018461
TI  - Template Preparation Affects 16S rRNA High-Throughput Sequencing Analysis of
      Phyllosphere Microbial Communities.
AB  - Phyllosphere microbial communities are highly diverse and have important
      ecological implications; in that context, bacterial identification based on 16S
      rRNA genes is an important research issue. In studies of phyllosphere microbial
      communities, microporous filtration and centrifugation are used to collect
      microorganism samples, but it is unclear which one has a better collection
      efficiency. In this study, we compared these two microorganism collection methods
      and investigated the effects of the DNA extraction process on the estimation of
      microbial community composition and organization. The following four treatments
      were examined: (A) filtration, resuspension, and direct PCR; (B) filtration, DNA
      isolation, and PCR; (C) centrifugation, resuspension, and direct PCR; (D)
      centrifugation, DNA isolation, and PCR. Our results showed that the percentage of
      chloroplast sequence contaminants was affected by the DNA extraction process. The
      bacterial compositions clearly differed between treatments A and C, suggesting
      that the collection method has an influence on the determination of community
      structure. Compared with treatments B and D, treatments A and C resulted in
      higher Shannon index values, indicating that the DNA extraction process might
      reduce the observed phyllosphere microbial alpha diversity. However, with respect
      to community structure, treatments B and D yielded very similar results,
      suggesting that the DNA extraction process erases the effect of the collection
      method. Our findings provide key information to ensure accurate estimates of
      diversity and community composition in studies of phyllosphere microorganisms.

PMID- 29018464
TI  - Comparison of Rooting Strategies to Explore Rock Fractures for Shallow Soil
      Adapted Tree Species with Contrasting Aboveground Growth Rates: A Greenhouse
      Microcosm Experiment.
AB  - For tree species adapted to shallow soil environments, rooting strategies that
      efficiently explore rock fractures are important because soil water depletion
      occurs frequently. However, two questions: (a) to what extent shallow soil
      adapted species rely on exploring rock fractures and (b) what outcomes result
      from drought stress, have rarely been tested. Therefore, based on the expectation
      that early development of roots into deep soil layers is at the cost of
      aboveground growth, seedlings of three tree species (Cyclobalanopsis glauca,
      Delavaya toxocarpa, and Acer cinnamomifolium) with distinct aboveground growth
      rates were selected from a typical shallow soil region. In a greenhouse
      experiment that mimics the basic features of shallow soil environments, 1-year
      old seedlings were transplanted into simulated microcosms of shallow soil
      overlaying fractured bedrock. Root biomass allocation and leaf physiological
      activities, as well as leaf delta13C values were investigated and compared for
      two treatments: regular irrigation and repeated cycles of drought stress. Our
      results show that the three species differed in their rooting strategies in the
      context of encountering rock fractures, however, these strategies were not
      closely related to the aboveground growth rate. For the slowest-growing seedling,
      C. glauca, percentages of root mass in the fractures, as well as in the soil
      layer between soil and bedrock increased significantly under both treatments,
      indicating a specialized rooting strategy that facilitated the exploration of
      rock fractures. Early investment in deep root growth was likely critical to the
      establishment of this drought-vulnerable species. For the intermediate-growing,
      A. cinnamomifolium, percentages of root mass in the bedrock and interface soil
      layers were relatively low and exhibited no obvious change under either
      treatment. This limited need to explore rock fractures was compensated by a
      conservative water use strategy. For the fast-growing, D. toxocarpa, percentages
      of root mass in the bedrock and interface layers increased simultaneously under
      drought conditions, but not under irrigated conditions. This drought-induced
      rooting plasticity was associated with drought avoidance by this species.
      Although, root development might have been affected by the simulated microcosm,
      contrasting results among the three species indicated that efficient use of rock
      fractures is not a necessary or specialized strategy of shallow-soil adapted
      species. The establishment and persistence of these species relied on the mutual
      complementation between their species-specific rooting strategies and drought
      adaptations.

PMID- 29018462
TI  - A Mini Zinc-Finger Protein (MIF) from Gerbera hybrida Activates the GASA Protein
      Family Gene, GEG, to Inhibit Ray Petal Elongation.
AB  - Petal appearance is an important horticultural trail that is generally used to
      evaluate the ornamental value of plants. However, knowledge of the molecular
      regulation of petal growth is mostly derived from analyses of Arabidopsis
      thaliana, and relatively little is known about this process in ornamental plants.
      Previously, GEG (Gerbera hybrida homolog of the gibberellin [GA]-stimulated
      transcript 1 [GAST1] from tomato), a gene from the GA stimulated Arabidopsis
      (GASA) family, was reported to be an inhibitor of ray petal growth in the
      ornamental species, G. hybrida. To explore the molecular regulatory mechanism of
      GEG in petal growth inhibition, a mini zinc-finger protein (MIF) was identified
      using yeast one-hybrid (Y1H) screen. The direct binding of GhMIF to the GEG
      promoter was verified by using an electrophoretic mobility shift assay and a dual
      luciferase assay. A yeast two-hybrid (Y2H) revealed that GhMIF acts as a
      transcriptional activator. Transient transformation assay indicated that GhMIF is
      involved in inhibiting ray petal elongation by activating the expression of GEG.
      Spatiotemporal expression analyses and hormone treatment assay showed that the
      expression of GhMIF and GEG is coordinated during petal development. Taken
      together, these results suggest that GhMIF acts as a direct transcriptional
      activator of GEG, a gene from the GASA protein family to regulate the petal
      elongation.

PMID- 29018465
TI  - Transgenic Centipedegrass (Eremochloa ophiuroides [Munro] Hack.) Overexpressing S
      Adenosylmethionine Decarboxylase (SAMDC) Gene for Improved Cold Tolerance Through
      Involvement of H2O2 and NO Signaling.
AB  - Centipedegrass (Eremochloa ophiuroides [Munro] Hack.) is an important warm-season
      turfgrass species. Transgenic centipedgrass plants overexpressing S
      adenosylmethionine decarboxylase from bermudagrass (CdSAMDC1) that was induced in
      response to cold were generated in this study. Higher levels of CdSAMDC1
      transcript and sperimidine (Spd) and spermin (Spm) concentrations and enhanced
      freezing and chilling tolerance were observed in transgenic plants as compared
      with the wild type (WT). Transgenic plants had higher levels of polyamine oxidase
      (PAO) activity and H2O2 than WT, which were blocked by pretreatment with
      methylglyoxal bis (guanylhydrazone) or MGBG, inhibitor of SAMDC, indicating that
      the increased PAO and H2O2 were a result of expression of CdSAMDC1. In addition,
      transgenic plants had higher levels of nitrate reductase (NR) activity and nitric
      oxide (NO) concentration. The increased NR activity were blocked by pretreatment
      with MGBG and ascorbic acid (AsA), scavenger of H2O2, while the increased NO
      level was blocked by MGBG, AsA, and inhibitors of NR, indicating that the
      enhanced NR-derived NO was dependent upon H2O2, as a result of expression
      CdSAMDC1. Elevated superoxide dismutase (SOD) and catalase (CAT) activities were
      observed in transgenic plants than in WT, which were blocked by pretreatment with
      MGBG, AsA, inhibitors of NR and scavenger of NO, indicating that the increased
      activities of SOD and CAT depends on expression of CdSAMDC1, H2O2, and NR-derived
      NO. Our results suggest that the elevated cold tolerance was associated with PAO
      catalyzed production of H2O2, which in turn led to NR-derived NO production and
      induced antioxidant enzyme activities in transgenic plants.

PMID- 29018463
TI  - The Plant Immunity Regulating F-Box Protein CPR1 Supports Plastid Function in
      Absence of Pathogens.
AB  - The redox imbalanced 6 mutant (rimb6) of Arabidopsis thaliana was isolated in a
      genetic screening approach for mutants with defects in chloroplast-to-nucleus
      redox signaling. It has an atypically low activation status of the 2-Cys
      peroxiredoxin-A promoter in the seedling stage. rimb6 shows wildtype-like
      germination, seedling development and greening, but slower growth and reduced
      biomass in the rosette stage. Mapping of the casual mutation revealed that rimb6
      carries a single nucleotide polymorphism in the gene encoding CONSTITUTIVE
      EXPRESSER OF PATHOGENESIS RELATED (PR) GENES 1, CPR1 (At4g12560), leading to a
      premature stop codon. CPR1 is known as a repressor of pathogen signaling and
      regulator of microtubule organization. Allelism of rimb6 and cpr1 revealed a
      function of CPR1 in chloroplast stress protection. Expression studies in pathogen
      signaling mutants demonstrated that CPR1-mediated activation of genes for
      photosynthesis and chloroplast antioxidant protection is, in contrast to
      activation of pathogen responses, regulated independently from PAD4-controlled
      salicylic acid (SA) accumulation. We conclude that the support of plastid
      function is a basic, SA-independent function of CPR1.

PMID- 29018467
TI  - Overexpression of SlGRAS40 in Tomato Enhances Tolerance to Abiotic Stresses and
      Influences Auxin and Gibberellin Signaling.
AB  - Abiotic stresses are major environmental factors that inhibit plant growth and
      development impacting crop productivity. GRAS transcription factors play critical
      and diverse roles in plant development and abiotic stress. In this study,
      SlGRAS40, a member of the tomato (Solanum lycopersicum) GRAS family, was
      functionally characterized. In wild-type (WT) tomato, SlGRAS40 was upregulated by
      abiotic stress induced by treatment with D-mannitol, NaCl, or H2O2. Transgenic
      tomato plants overexpressing SlGRAS40 (SlGRAS40-OE) were more tolerant of drought
      and salt stress than WT. SlGRAS40-OE plants displayed pleiotropic phenotypes
      reminiscent of those resulting from altered auxin and/or gibberellin signaling. A
      comparison of WT and SlGRAS40-OE transcriptomes showed that the expression of a
      large number of genes involved in hormone signaling and stress responses were
      modified. Our study of SlGRAS40 protein provides evidence of how another GRAS
      plays roles in resisting abiotic stress and regulating auxin and gibberellin
      signaling during vegetative and reproductive growth in tomato.

PMID- 29018466
TI  - Differential Lipid Composition and Gene Expression in the Semi-Russeted "Cox
      Orange Pippin" Apple Variety.
AB  - Russeting is characterized by a particular rough and brown phenotype, which is
      mainly due to the accumulation of suberin in the inner part of the epidermal cell
      walls. In our previous bulk transcriptomic analysis, comparing fully russeted,
      and waxy apple varieties, showed, in apple fruit skin, a massive decreased
      expression of cutin, wax and some pentacyclic triterpene biosynthesis genes in
      the russeted varieties, with an expected concomitant enhanced expression of the
      suberin biosynthetic genes. In the present work, we performed a deep
      investigation of the aliphatic composition of the cutin, suberin, waxes, and
      triterpenes in the waxy and russeted patches of the semi-russeted apple variety
      "Cox Orange Pippin." A targeted gene expression profiling was performed to
      validate candidate genes which were identified in our previous work and might be
      involved in the respective metabolic pathways. Our results showed that a decrease
      of cuticular waxes, ursolic acid and oleanolic acid, accompanied by an
      accumulation of alkyl-hydroxycinamates and betulinic acid, occurs in the russeted
      patches. The suberin monomer composition is characterized by specific occurrence
      of 20, 22, and 24 carbon aliphatic chains, whereas cutin is mainly represented by
      common C16 and C18 aliphatic chains. This work depicts, for the first time in
      apple, the complex composition of suberin, cutin, waxes and triterpenes, and
      confirms the strong interplay between these epidermal polymers in apple fruit
      skin.

PMID- 29018468
TI  - Legume Shrubs Are More Nitrogen-Homeostatic than Non-legume Shrubs.
AB  - Legumes are characterized as keeping stable nutrient supply under nutrient
      limited conditions. However, few studies examined the legumes' stoichiometric
      advantages over other plants across various taxa in natural ecosystems. We
      explored differences in nitrogen (N) and phosphorus (P) stoichiometry of
      different tissue types (leaf, stem, and root) between N2-fixing legume shrubs and
      non-N2-fixing shrubs from 299 broadleaved deciduous shrubland sites in northern
      China. After excluding effects of taxonomy and environmental variables, these two
      functional groups differed considerably in nutrient regulation. N concentrations
      and N:P ratios were higher in legume shrubs than in non-N2-fixing shrubs. N
      concentrations were positively correlated between the plants and soil for non-N2
      fixing shrubs, but not for legume shrubs, indicating a stronger stoichiometric
      homeostasis in legume shrubs than in non-N2-fixing shrubs. N concentrations were
      positively correlated among three tissue types for non-N2-fixing shrubs, but not
      between leaves and non-leaf tissues for legume shrubs, demonstrating that N
      concentrations were more dependent among tissues for non-N2-fixing shrubs than
      for legume shrubs. N and P concentrations were correlated within all tissues for
      both functional groups, but the regression slopes were flatter for legume shrubs
      than non-N2-fixing shrubs, implying that legume shrubs were more P limited than
      non-N2-fixing shrubs. These results address significant differences in
      stoichiometry between legume shrubs and non-N2-fixing shrubs, and indicate the
      influence of symbiotic nitrogen fixation (SNF) on plant stoichiometry. Overall,
      N2-fixing legume shrubs are higher and more stoichiometrically homeostatic in N
      concentrations. However, due to excess uptake of N, legumes may suffer from
      potential P limitation. With their N advantage, legume shrubs could be good nurse
      plants in restoration sites with degraded soil, but their P supply should be
      taken care of during management according to our results.

PMID- 29018469
TI  - De Novo Assembly of Transcriptome and Development of Novel EST-SSR Markers in
      Rhododendron rex Levl. through Illumina Sequencing.
AB  - Transcriptome sequences generated by next-generation sequencing (NGS)
      technologies can be utilized to rapidly detect and characterize a large number of
      gene-based microsatellites from different plants. Rhododendron rex Levl. is a
      perennial woody species from the family Ericaceae and an endangered plant with
      high ornamental value endemic to Southwestern China. Nevertheless, the genetic
      and genomic information of R. rex remain unknown. In this study, we performed
      transcriptome sequencing for R. rex leaf samples, and generated large transcript
      sequences for functional characterization and development gene-associated SSR
      markers. A total of 164,242 unigenes were assembled and 115,089 (70.07%) unigenes
      were successfully annotated in public databases. In addition, a total of 15,314
      potential EST-SSRs were identified, and the frequency of SSRs in the R. rex
      unigenes was 9.32%, with an average of one EST-SSR per 5.65 kb. The most abundant
      type was repeated di-nucleotide (54.63%), followed by mono- (26.03%) and tri
      nucleotide (18.51%) repeats. Based on the SSR-containing sequence, 100 primer
      pairs were randomly selected and synthesized and used for assessment of the
      polymorphism. Thirty-six primer pairs were polymorphic and revealed polymorphism
      among 20 individuals from four R. rex populations. A total of 197 alleles were
      identified, with an average of 5.472 alleles per locus. The Polymorphism
      Information Content ranged from 0.154 to 0.870, with a mean of 0.482. The newly
      developed EST-SSR markers exhibited high transferability (58.33-83.33%) among the
      six subgenera. Thus, these novel EST-SSR markers developed would provide valuable
      sequence resources for population structure, genetic diversity analysis, and
      genetic resource assessments of R. rex and its related species.

PMID- 29018470
TI  - Phakopsora euvitis Causes Unusual Damage to Leaves and Modifies Carbohydrate
      Metabolism in Grapevine.
AB  - Asian grapevine rust (Phakopsora euvitis) is a serious disease, which causes
      severe leaf necrosis and early plant defoliation. These symptoms are unusual for
      a strict biotrophic pathogen. This work was performed to quantify the effects of
      P. euvitis on photosynthesis, carbohydrates, and biomass accumulation of
      grapevine. The reduction in photosynthetic efficiency of the green leaf tissue
      surrounding the lesions was quantified using the virtual lesion concept (beta
      parameter). Gas exchange and responses of CO2 assimilation to increasing
      intercellular CO2 concentration were analyzed. Histopathological analyses and
      quantification of starch were also performed on diseased leaves. Biomass and
      carbohydrate accumulation were quantified in different organs of diseased and
      healthy plants. Rust reduced the photosynthetic rate, and beta was estimated at
      5.78, indicating a large virtual lesion. Mesophyll conductance, maximum rubisco
      carboxylation rate, and regeneration of ribulose-1,5-bisphosphate dependent on
      electron transport rate were reduced, causing diffusive and biochemical
      limitations to photosynthesis. Hypertrophy, chloroplast degeneration of mesophyll
      cells, and starch accumulation in cells close to lesions were observed. Root
      carbohydrate concentration was reduced, even at low rust severity. Asian
      grapevine rust dramatically reduced photosynthesis and altered the dynamics of
      production and accumulation of carbohydrates, unlike strict biotrophic pathogens.
      The reduction in carbohydrate reserves in roots would support polyetic damage on
      grapevine, caused by a polycyclic disease.

PMID- 29018472
TI  - Germination and Seedling Growth of Water Primroses: A Cross Experiment between
      Two Invaded Ranges with Contrasting Climates.
AB  - Aquatic ecosystems are vulnerable to biological invasions, and will also be
      strongly impacted by climate change, including temperature increase.
      Understanding the colonization dynamics of aquatic invasive plant species is of
      high importance for preservation of native biodiversity. Many aquatic invasive
      plants rely on clonal reproduction to spread, but mixed reproductive modes are
      common. Under future climate changes, these species may favor a sexual
      reproductive mode. The aim of this study was to test the germination capacity and
      the seedling growth of two water primrose species, Ludwigia hexapetala and
      Ludwigia peploides, both invasive in Europe and in the United States. We
      performed a reciprocal transplant of seeds of L. hexapetala and L. peploides from
      two invasive ranges into experimental gardens characterized by Oceanic and
      Mediterranean-type climates. Our results showed that higher temperatures
      increased or maintained germination percentages and velocity, decreased
      survivorship of germinants, but increased their production of biomass. The origin
      of the seeds had low impact on L. hexapetala responses to temperature, but
      greatly influenced those of L. peploides. The invasiveness of water primroses in
      ranges with Oceanic climates might increase with temperature. The recruitment
      from seed banks by these species should be considered by managers to improve the
      conservation of native aquatic and wetland plant species.

PMID- 29018473
TI  - QTL Analyses in Multiple Populations Employed for the Fine Mapping and
      Identification of Candidate Genes at a Locus Affecting Sugar Accumulation in
      Melon (Cucumis melo L.).
AB  - Sugar content is the major determinant of both fruit quality and consumer
      acceptance in melon (Cucumis melo L), and is a primary target for crop
      improvement. Near-isogenic lines (NILs) derived from the intraspecific cross
      between a "Piel de Sapo" (PS) type and the exotic cultivar "Songwhan Charmi"
      (SC), and several populations generated from the cross of PS * Ames 24294
      ("Trigonus"), a wild melon, were used to identify QTL related to sugar and
      organic acid composition. Seventy-eight QTL were detected across several
      locations and different years, with three important clusters related to sugar
      content located on chromosomes 4, 5, and 7. Two PS * SC NILs (SC5-1 and SC5-2)
      sharing a common genomic interval of 1.7 Mb at the top of chromosome 5 contained
      QTL reducing soluble solids content (SSC) and sucrose content by an average of 29
      and 68%, respectively. This cluster collocated with QTL affecting sugar content
      identified in other studies in lines developed from the PS * SC cross and
      supported the presence of a stable consensus locus involved in sugar accumulation
      that we named SUCQSC5.1. QTL reducing soluble solids and sucrose content
      identified in the "Trigonus" mapping populations, as well as QTL identified in
      previous studies from other ssp. agrestis sources, collocated with SUCQSC5.1,
      suggesting that they may be allelic and implying a role in domestication. In
      subNILs derived from the PS * SC5-1 cross, SUCQSC5.1 reduced SSC and sucrose
      content by an average of 18 and 34%, respectively, and was fine-mapped to a 56.1
      kb interval containing four genes. Expression analysis of the candidate genes in
      mature fruit showed differences between the subNILs with PS alleles that were
      "high" sugar and SC alleles of "low" sugar phenotypes for MELO3C014519, encoding
      a putative BEL1-like homeodomain protein. Sequence differences in the gene
      predicted to affect protein function were restricted to SC and other ssp.
      agrestis cultivar groups. These results provide the basis for further
      investigation of genes affecting sugar accumulation in melon.

PMID- 29018471
TI  - Diverse Roles of Ethylene in Regulating Agronomic Traits in Rice.
AB  - Gaseous hormone ethylene has diverse effects in various plant processes. These
      processes include seed germination, plant growth, senescence, fruit ripening,
      biotic and abiotic stresses responses, and many other aspects. The biosynthesis
      and signaling of ethylene have been extensively studied in model Arabidopsis in
      the past two decades. However, knowledge about the ethylene signaling mechanism
      in crops and roles of ethylene in regulation of crop agronomic traits are still
      limited. Our recent findings demonstrate that rice possesses both conserved and
      diverged mechanism for ethylene signaling compared with Arabidopsis. Here, we
      mainly focused on the recent advances in ethylene regulation of important
      agronomic traits. Of special emphasis is its impact on rice growth, flowering,
      grain filling, and grain size control. Similarly, the influence of ethylene on
      other relevant crops will be compared. Additionally, interactions of ethylene
      with other hormones will also be discussed in terms of crop growth and
      development. Increasing insights into the roles and mechanisms of ethylene in
      regulating agronomic traits will contribute to improvement of crop production
      through precise manipulation of ethylene actions in crops.

PMID- 29018475
TI  - The MicroRNA Interaction Network of Lipid Diseases.
AB  - Background: Dyslipidemia is one of the major forms of lipid disorder,
      characterized by increased triglycerides (TGs), increased low-density lipoprotein
      cholesterol (LDL-C), and decreased high-density lipoprotein-cholesterol (HDL-C)
      levels in blood. Recently, MicroRNAs (miRNAs) have been reported to involve in
      various biological processes; their potential usage being a biomarkers and in
      diagnosis of various diseases. Computational approaches including text mining
      have been used recently to analyze abstracts from the public databases to observe
      the relationships/associations between the biological molecules, miRNAs, and
      disease phenotypes. Materials and Methods: In the present study, significance of
      text mined extracted pair associations (miRNA-lipid disease) were estimated by
      one-sided Fisher's exact test. The top 20 significant miRNA-disease associations
      were visualized on Cytoscape. The CyTargetLinker plug-in tool on Cytoscape was
      used to extend the network and predicts new miRNA target genes. The Biological
      Networks Gene Ontology (BiNGO) plug-in tool on Cytoscape was used to retrieve
      gene ontology (GO) annotations for the targeted genes. Results: We retrieved 227
      miRNA-lipid disease associations including 148 miRNAs. The top 20 significant
      miRNAs analysis on CyTargetLinker provides defined, predicted and validated gene
      targets, further targeted genes analyzed by BiNGO showed targeted genes were
      significantly associated with lipid, cholesterol, apolipoprotein, and fatty acids
      GO terms. Conclusion: We are the first to provide a reliable miRNA-lipid disease
      association network based on text mining. This could help future experimental
      studies that aim to validate predicted gene targets.

PMID- 29018474
TI  - Six-Year Nitrogen-Water Interaction Shifts the Frequency Distribution and Size
      Inequality of the First-Order Roots of Fraxinus mandschurica in a Mixed Mature
      Pinus koraiensis Forest.
AB  - The variation in fine root traits in terms of size inequality at the individual
      root level can be identified as a strategy for adapting to the drastic changes in
      soil water and nutrient availabilities. The Gini and Lorenz asymmetry
      coefficients have been applied to describe the overall degree of size inequality,
      which, however, are neglected when conventional statistical means are calculated.
      Here, we used the Gini coefficient, Lorenz asymmetry coefficient and statistical
      mean in an investigation of Fraxinus mandschurica roots in a mixed mature Pinus
      koraiensis forest on Changbai Mountain, China. We analyzed 967 individual roots
      to determine the responses of length, diameter and area of the first-order roots
      and of branching intensity to 6 years of nitrogen addition (N), rainfall
      reduction (W) and their combination (NW). We found that first-order roots had a
      significantly greater average length and area but had smaller Gini coefficients
      in NW plots compared to in control plots (CK). Furthermore, the relationship
      between first-order root length and branching intensity was negative in CK, N,
      and W plots but positive in NW plots. The Lorenz asymmetry coefficient was >1 for
      the first-order root diameter in NW and W plots as well as for branching
      intensity in N plots. The bimodal frequency distribution of the first-order root
      length in NW plots differed clearly from the unimodal one in CK, N, and W plots.
      These results demonstrate that not only the mean but also the variation and the
      distribution mode of the first-order roots of F. mandschurica respond to soil
      nitrogen and water availability. The changes in size inequality of the first
      order root traits suggest that Gini and Lorenz asymmetry coefficients can serve
      as informative parameters in ecological investigations of roots to improve our
      ability to predict how trees will respond to a changing climate at the individual
      root level.

PMID- 29018476
TI  - Recurrent and Prolonged Infections in a Child with a Homozygous IFIH1 Nonsense
      Mutation.
AB  - In an Egyptian girl born to consanguineous parents, whole-exome sequencing (WES)
      identified a homozygous mutation in PHGDH, c.1273G>A (p.Val425Met), indicating 3
      phosphoglycerate dehydrogenase deficiency. This diagnosis was compatible with the
      patient's microcephaly, severe psychomotor retardation, seizures and cataracts.
      However, she additionally suffered from recurrent (at least monthly) episodes of
      prolonged and severe chest infections requiring hospitalization, suggesting a
      secondary, predisposing and potentially Mendelian, condition. A local
      reactivation of an EBV infection in the respiratory tract was detected after a
      recent chest infection, likely representing an opportunistic infection based on a
      compromised immune system. Further inspection of WES data revealed a homozygous
      nonsense mutation, c.2665A>T (p.Lys889*), in IFIH1, encoding MDA5. MDA5 detects
      long viral double-stranded RNA that is generated during replication of picorna
      viruses, and thereby activates the type I interferon signaling pathway. The
      results of Western blot analysis of protein from cultured fibroblasts of the
      patient indicates absence of wild type MDA5/IFIH1, compatible with NMD. We
      propose that, analogous to the severe course of primary influenza infection due
      to biallelic deficiency of a downstream effector, IRF7, homozygous loss of IFIH1
      defines a novel Mendelian immunodeficiency disorder that increases susceptibility
      to severe viral infections. This is contrasted to heterozygous gain-of-function
      IFIH1 mutations in autoimmune diseases. Our findings highlight the potential of
      comprehensive genomic investigations in patients from consanguineous families to
      identify monogenic predispositions to severe infections.

PMID- 29018477
TI  - Commentary: Grand challenge: ELSI in a changing global environment.

PMID- 29018478
TI  - Ultrafast Comparison of Personal Genomes via Precomputed Genome Fingerprints.
AB  - We present an ultrafast method for comparing personal genomes. We transform the
      standard genome representation (lists of variants relative to a reference) into
      "genome fingerprints" via locality sensitive hashing. The resulting genome
      fingerprints can be meaningfully compared even when the input data were obtained
      using different sequencing technologies, processed using different pipelines,
      represented in different data formats and relative to different reference
      versions. Furthermore, genome fingerprints are robust to up to 30% missing data.
      Because of their reduced size, computation on the genome fingerprints is fast and
      requires little memory. For example, we could compute all-against-all pairwise
      comparisons among the 2504 genomes in the 1000 Genomes data set in 67 s at high
      quality (21 MUs per comparison, on a single processor), and achieved a lower
      quality approximation in just 11 s. Efficient computation enables scaling up a
      variety of important genome analyses, including quantifying relatedness,
      recognizing duplicative sequenced genomes in a set, population reconstruction,
      and many others. The original genome representation cannot be reconstructed from
      its fingerprint, effectively decoupling genome comparison from genome
      interpretation; the method thus has significant implications for privacy
      preserving genome analytics.

PMID- 29018480
TI  - Comparison of Esophageal Function Tests in Chinese Patients with Functional
      Heartburn and Reflux Hypersensitivity.
AB  - OBJECTIVE: To investigate the differences in the results of esophageal function
      tests for functional heartburn (FH) and reflux hypersensitivity (RH). METHODS:
      Patients with FH and RH and healthy volunteers (HVs) from the Department of
      Gastroenterology, Beijing Anzhen Hospital and Beijing Chao-Yang hospital, who
      underwent high-resolution manometry and impedance (HRIM), and 24-hour
      multichannel intraluminal impedance and pH recording (MII/pH) between 2014 and
      2016, were enrolled in this study. RESULTS: 36 HV, 147 FH patients, and 91 RH
      patients were enrolled. The postreflux swallow-induced peristaltic wave index
      (PSPW index) and mean nocturnal baseline impedance (MNBI) values were
      significantly lower in RH than in FH and HV. The ineffective esophageal motility
      (IEM), fragmented peristalsis rates, total bolus exposure, proximal total reflux
      events, and distal total reflux events were significantly greater in RH than in
      FH and HV. CONCLUSIONS: Compared to HV and FH patients, RH patients exhibited
      greater IEM and fragmented peristalsis rates, a greater total bolus exposure,
      more proximal total and distal total reflux events, and reduced chemical
      clearance and mucosal integrity. By using the above described parameters, HRIM
      and MII/pH assays could be used to correctly classify RH and FH and hence allow
      physicians to provide adequate relief from associated symptoms.

PMID- 29018481
TI  - Comparative Study between Plastic and Metallic Stents for Biliary Decompression
      in Patients with Distal Biliary Obstruction.
AB  - This paper presents a retrospective comparison of plastic versus metallic stents
      in the drainage of malignant distal biliary obstructions. We compared single
      plastic stents (SPS), multiple plastic stents (MPS), and metallic stents (SEMS)
      regarding clinical decrease of TB < 2.0 mg/dL, long-term patency, and adverse
      event. 58 patients (38 women) with MDBO were included. Diagnoses were 44
      pancreatic adenocarcinoma (74.6%), 9 metastasis (15.5%), 3 pancreatic
      neuroendocrine tumors (5.1%), and 2 adenocarcinoma in the major papilla (3.4%).
      The number of patients included in the SPS, MPS, and SEMS was 17, 6, and 35,
      respectively. Comparing the survival curves with respect to obstruction, we
      observed a lower mean permeability of the SPS compared to that of the MPS with p
      < 0.003 and of the SEMS group (p < 0.01). There was no statistical difference
      between the use of MPS, despite the small number of patients compared to the use
      of SEMS (p < 0.13) to reach the satisfactory levels of bilirubin.

PMID- 29018479
TI  - Epigenetic Regulation of Cellular Senescence and Aging.
AB  - Aging is characterized by functional decline of diverse organs and an increased
      risk for several diseases. Therefore, a high interest exists in understanding the
      molecular mechanisms that stimulate aging at all levels, from cells and tissues
      to organs and organisms, in order to develop ways to promote healthy aging. While
      many molecular and biochemical mechanisms are already understood in some detail,
      the role of changes in epigenetic regulation has only begun to be considered in
      recent years. The age-dependent global reduction in heterochromatin, along with
      site-specific changes in the patterns of DNA methylation and modification of
      histones, have been observed in several aging model systems. However,
      understanding of the precise role of such changes requires further research. In
      this review, we will discuss the role of epigenetic regulation in aging and
      indicate future research directions that will help elucidate the mechanistic
      details of it.

PMID- 29018482
TI  - The Advances of Laparoscopic Gastrectomy for Gastric Cancer.
AB  - Laparoscopic gastrectomy is evolving. With the increasing expertise and
      experience of oncologic surgeons in the minimally invasive surgery for gastric
      cancer, the indication for laparoscopic gastrectomy is expanding to advanced
      cases. Many studies have demonstrated the benefits of minimally invasive surgery,
      including reduced risk of surgery-related injury, reduced blood loss, less pain,
      and earlier recovery. In order to establish concrete evidence for the suitability
      of minimal invasive surgery for gastric cancer, many multicenter RCTs, comparing
      the short- and long-term outcomes of laparoscopic versus open surgery, are in
      progress. Advances in laparoscopic gastrectomy are moving toward increasingly
      minimally invasive approaches that enable the improvement of the quality of life
      of patients, without compromising on oncologic safety.

PMID- 29018483
TI  - The Angiogenic Potential of DPSCs and SCAPs in an In Vivo Model of Dental Pulp
      Regeneration.
AB  - Adequate vascularization, a restricting factor for the survival of engineered
      tissues, is often promoted by the addition of stem cells or the appropriate
      angiogenic growth factors. In this study, human dental pulp stem cells (DPSCs)
      and stem cells from the apical papilla (SCAPs) were applied in an in vivo model
      of dental pulp regeneration in order to compare their regenerative potential and
      confirm their previously demonstrated paracrine angiogenic properties. 3D-printed
      hydroxyapatite scaffolds containing DPSCs and/or SCAPs were subcutaneously
      transplanted into immunocompromised mice. After twelve weeks, histological and
      ultrastructural analysis demonstrated the regeneration of vascularized pulp-like
      tissue as well as mineralized tissue formation in all stem cell constructs.
      Despite the secretion of vascular endothelial growth factor in vitro, the stem
      cell constructs did not display a higher vascularization rate in comparison to
      control conditions. Similar results were found after eight weeks, which suggests
      both osteogenic/odontogenic differentiation of the transplanted stem cells and
      the promotion of angiogenesis in this particular setting. In conclusion, this is
      the first study to demonstrate the successful formation of vascularized pulp-like
      tissue in 3D-printed scaffolds containing dental stem cells, emphasizing the
      promising role of this approach in dental tissue engineering.

PMID- 29018485
TI  - Stem Cell-Based Therapy in Transplantation and Immune-Mediated Diseases.

PMID- 29018486
TI  - Serum and Liver Tissue Metabonomic Study on Fatty Liver in Rats Induced by High
      Fat Diet and Intervention Effects of Traditional Chinese Medicine Qushi Huayu
      Decoction.
AB  - Qushi Huayu Decoction (QSHY), clinically derived, consists of five crude drugs,
      commonly used in treating fatty liver in a clinical setting. However, little is
      known about its metabolomics study. Herein, the serum and liver tissue
      metabolomics approach, based on gas chromatography coupled to spectrometry
      (GC/MS), was employed to evaluate the efficacy and the mechanism underlying QSHY
      in a rat model of high-fat diet-induced fatty liver. With pattern recognition
      analysis of serum and liver tissue metabolite profile, a clear separation of
      model group and control group was acquired for serum and liver tissue samples,
      respectively. The QSHY group showed a predisposition towards recovery mimicking
      the control group, which was in agreement with the biochemical alterations and
      histological results. 23 candidate biomarkers were identified in the serum and
      liver tissue samples that were utilized for exploring the underlying mechanism.
      The present study suggests that QSHY has significant anti-fatty liver effects on
      high-fat diet-induced fatty liver in rats, which might be attributed to
      regulating the dysfunction of beta-alanine metabolism, alanine, aspartate, and
      glutamate metabolism, glycine, serine, and threonine metabolism, pyruvate
      metabolism, and citrate cycle. Thus, metabolomics is a useful tool in the
      evaluation of the efficacy and elucidation of the mechanism underlying the
      complex traditional Chinese medicine prescriptions.

PMID- 29018484
TI  - Infrapatellar Fat Pad Stem Cells: From Developmental Biology to Cell Therapy.
AB  - The ideal cell type to be used for cartilage therapy should possess a proven
      chondrogenic capacity, not cause donor-site morbidity, and should be readily
      expandable in culture without losing their phenotype. There are several cell
      sources being investigated to promote cartilage regeneration: mature articular
      chondrocytes, chondrocyte progenitors, and various stem cells. Most recently,
      stem cells isolated from joint tissue, such as chondrogenic stem/progenitors from
      cartilage itself, synovial fluid, synovial membrane, and infrapatellar fat pad
      (IFP) have gained great attention due to their increased chondrogenic capacity
      over the bone marrow and subcutaneous adipose-derived stem cells. In this review,
      we first describe the IFP anatomy and compare and contrast it with other adipose
      tissues, with a particular focus on the embryological and developmental aspects
      of the tissue. We then discuss the recent advances in IFP stem cells for
      regenerative medicine. We compare their properties with other stem cell types and
      discuss an ontogeny relationship with other joint cells and their role on in vivo
      cartilage repair. We conclude with a perspective for future clinical trials using
      IFP stem cells.

PMID- 29018487
TI  - The Effects of Curcumin on Wound Healing in a Rat Model of Nasal Mucosal Trauma.
AB  - We explored the effects of topical curcumin on the healing of nasal mucosal
      wounds. A total of 32 Sprague-Dawley Albino rats were randomized in equal numbers
      into four groups, and unilateral nasal wounds were created using an interdental
      brush. Group 1 (the sham-control group) contained untreated rats with traumatized
      right-side nasal cavities; Group 2 and 3 rats were similarly traumatized and
      treated with topical curcumin (5 and 10 mg/mL) dissolved in dimethyl sulfoxide
      daily for 7 days after trauma; Group 4 rats were treated with topical dimethyl
      sulfoxide only. All rats were decapitated on day 15 and the healing sites
      evaluated by blinded observers in terms of the presence of cellular hyperplasia,
      goblet cell hypertrophy and degeneration, leucocytic infiltration, ciliary loss
      and degeneration, edema, and vascular dilation. On histopathological evaluation,
      all of cellular hyperplasia, leukocytic infiltration, and edema were
      significantly reduced in Group 3 compared with Group 1 (p = 0.001, p = 0.004, and
      p = 0.008, resp.). Thus, curcumin reduced the inflammatory response and
      significantly accelerated wound healing.

PMID- 29018488
TI  - Higher resting metabolic rate in long-lived breeding Ansell's mole-rats (Fukomys
      anselli).
AB  - BACKGROUND: Reproduction is an energetically expensive process that supposedly
      impairs somatic integrity in the long term, because resources are limited and
      have to be allocated between reproduction and somatic maintenance, as predicted
      by the life history trade-off model. The consequence of reduced investment in
      somatic maintenance is a gradual deterioration of function, i.e. senescence.
      However, this classical trade-off model gets challenged by an increasing number
      of contradicting studies. Here we report about an animal model, which adds more
      complexity to the ongoing debate. Ansell's mole-rats are long-lived social
      subterranean rodents with only the founder pair reproducing, while most of their
      offspring remain in the parental burrow system and do not breed. Despite of a
      clear reproductive trade-off, breeders live up to twice as long as non-breeders,
      a unique feature amongst mammals. METHODS: We investigated mass-specific resting
      metabolic rates (msRMR) of breeders and non-breeders to gain information about
      the physiological basis underlying the reproduction-associated longevity in
      Ansell's mole-rats. We assessed the thermoneutral zone (TNZ) for breeders and non
      breeders separately by means of indirect calorimetry. We applied generalized
      linear mixed-effects models for repeated measurements using the msRMR in the
      respective TNZs. RESULTS: TNZ differed between reproductive and non-reproductive
      Ansell's mole-rats. Contrary to classical aging models, the shorter-lived non
      breeders had significantly lower msRMR within the thermoneutral zone compared to
      breeders. CONCLUSION: This is the first study reporting a positive correlation
      between msRMR and lifespan based on reproductive status. Our finding contradicts
      common aging theories, but supports recently introduced models which do not
      necessarily link reproductive trade-offs to lifespan reduction.

PMID- 29018489
TI  - Effects of resveratrol on glucose control and insulin sensitivity in subjects
      with type 2 diabetes: systematic review and meta-analysis.
AB  - Although the regular consumption of resveratrol has been known to improve glucose
      homeostasis and reverse insulin resistance in type 2 diabetes mellitus (T2DM),
      the reported results are inconsistent. Thus, we aimed to assess the effects of
      resveratrol on glycemic control and insulin sensitivity among patients with T2DM.
      We searched for relevant articles published until June 2017 on PubMed-Medline,
      Embase, Cochrane Library, and Web of Science. Randomized controlled trials in
      T2DM patients administered with resveratrol as intervention were included. After
      study selection, quality assessment and data extraction were performed
      independently by two authors, and STATA and RevMan software were used for
      statistical analysis. Nine randomized controlled trials involving 283
      participants were included. Meta-analysis showed that resveratrol significantly
      improved the fasting plasma glucose ( -0.29 mmol/l, 95% CI: -0.51, -0.06, p <
      0.01) and insulin levels (-0.64 U/mL, 95% CI: -0.95, -0.32, p < 0.0001). The drug
      also reduced homeostasis model assessment of insulin resistance (HOMA-IR) index,
      systolic blood pressure, and diastolic blood pressure among participants with
      T2DM. The changes in hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol,
      and high-density lipoprotein cholesterol were negligible. Subgroup analysis
      comparing the resveratrol supplementation doses of < 100 mg/d versus >= 100 mg/d
      revealed a significant difference in fasting plasma glucose. In particular, the
      latter dose presented more favorable results. This meta-analysis provides
      evidence that supplementation of resveratrol may benefit management of T2DM.

PMID- 29018491
TI  - Perception of Noise Pollution in a Youth and Adults School in Curitiba-PR.
AB  - Introduction  Nowadays noise remains the third largest cause of environmental
      pollution on Earth. It appears that despite the existing noise control
      legislation the issue deserves further supervision by the public authorities so
      that the ceilings established for the various activities are observed. People
      exposed to noise are more likely to develop numerous auditory and non-auditory
      problems directly impacting persona family and working life. Objectives  The
      objective of this study is to research and consequently understand how the
      population of students of a youth and adult school in Curitiba perceives noise
      pollution as well as look into the actions that the school adopts in order to
      guide the students on the topic. Method  We applied a structured questionnaire to
      120 individuals and assessed the following variables: characterization of the
      place of residence occupation leisure health and perception of soundscapes. We
      also applied a closed questionnaire about educational actions for noise pollution
      to the school's geography teacher. Results  Questionnaire responses show that
      people perceive noise in the most diverse environments they frequent and are able
      to identify the source of the noise but this perception proved fragile as the
      majority does not take measures to prevent or mitigate these noises. At school
      there are no actions aimed at environmental education on the subject studied.
      Conclusion  The studied group does not perceive the noise as a harmful agent and
      does not prevent themselves from it and the school not work contents related to
      noise pollution leaving a significant gap in the awareness process of this
      population.

PMID- 29018490
TI  - The promotion of nephropathy by Porphyromonas gingivalis lipopolysaccharide via
      toll-like receptors.
AB  - BACKGROUND: Recently, we reported that toll-like receptor (TLR)2 and TLR4
      localized on the glomerular endothelium in the glomeruli of streptozotocin (STZ)
      induced type 1 diabetic mice and high fat diet feed-induced type 2 diabetic mice,
      and that periodontal pathogen Porphyromonas gingivalis LPS (Pg-LPS)
      administration lowered the survival rate of diabetic mice. The present study aims
      to examine the effect of TLR4 blocking on the suppression of Pg-LPS-induced
      diabetic nephropathy. METHODS: The survival rate and morphological/biochemical
      features for streptozotocin-induced diabetic mice with Pg-LPS and TLR4 blocker
      eritoran administration were investigated by reporter gene assay, urine and blood
      analysis, immunohistochemistry, and real time-PCR. RESULTS AND CONCLUSIONS: All
      of the diabetic mice administered Pg-LPS were euthanized within the survival
      period of almost all of the diabetic mice. The blood urea nitrogen and
      creatinine, expression of TLR2 and TGF-b, and type 1 collagen accumulation, in
      the diabetic mice increased significantly with the Pg-LPS administration. In
      spite of the limited TLR4 activation with Pg-LPS, the TLR4 blocker eritoran
      decreased blood urea nitrogen and creatinine, and raised the survival rate of the
      Pg-LPS-administered diabetic mice slightly. The high expression levels of TLR2,
      TGF-b, and type 1 collagen in Pg-LPS-administered diabetic mice decreased with
      eritoran. Nuclear STAT3 which enhances TLR2 expression was detected in the TLR2
      expressing glomeruli of diabetic mice. The TLR2 and STAT3 gene expression
      increased by the Pg-LPS administration but decreased with eritoran. These may
      suggest that Pg-LPS-induced diabetic nephropathy is mainly dependent on TLR2
      signaling on glomerular endothelial cells, and that TLR4 blocker eritoran may
      play a role to slow the progress of diabetic nephropathy.

PMID- 29018492
TI  - Air and Bone Conduction Frequency-specific Auditory Brainstem Response in
      Children with Agenesis of the External Auditory Canal.
AB  - Introduction  The tone-evoked auditory brainstem responses (tone-ABR) enable the
      differential diagnosis in the evaluation of children until 12 months of age,
      including those with external and/or middle ear malformations. The use of
      auditory stimuli with frequency specificity by air and bone conduction allows
      characterization of hearing profile. Objective  The objective of our study was to
      compare the results obtained in tone-ABR by air and bone conduction in children
      until 12 months, with agenesis of the external auditory canal. Method  The study
      was cross-sectional, observational, individual, and contemporary. We conducted
      the research with tone-ABR by air and bone conduction in the frequencies of 500
      Hz and 2000 Hz in 32 children, 23 boys, from one to 12 months old, with agenesis
      of the external auditory canal. Results  The tone-ABR thresholds were
      significantly elevated for air conduction in the frequencies of 500 Hz and 2000
      Hz, while the thresholds of bone conduction had normal values in both ears. We
      found no statistically significant difference between genders and ears for most
      of the comparisons. Conclusion  The thresholds obtained by bone conduction did
      not alter the thresholds in children with conductive hearing loss. However, the
      conductive hearing loss alter all thresholds by air conduction. The tone-ABR by
      bone conduction is an important tool for assessing cochlear integrity in children
      with agenesis of the external auditory canal under 12 months.

PMID- 29018493
TI  - Variation in the Hearing Threshold in Women during the Menstrual Cycle.
AB  - Introduction  The hormonal changes that occur during the menstrual cycle and
      their relationship with hearing problems have been studied. However, they have
      not been well explained. Objective  The objective of our study is to investigate
      the variation in hearing thresholds in women during the menstrual cycle. Method 
      We conducted a cohort and longitudinal study. It was composed of 30 volunteers,
      aged 18-39 years old, of which 20 were women during the phases of the menstrual
      cycle and 10 were men (control group) who underwent audiometry and impedance
      exams, to correlate the possible audiological changes in each phase of the
      menstrual cycle. Results  There were significant changes in hearing thresholds
      observed during the menstrual cycle phases in the group of women who used
      hormonal contraceptives and the group who did not use such contraceptives.
      Improved hearing thresholds were observed in the late follicular phase in the
      group who did not use hormonal contraceptives and the hearing thresholds at high
      frequencies were better. Throughout the menstrual cycle phases, the mean
      variation was 3.6 db HL between weeks in the group who used hormonal
      contraceptives and 4.09 db HL in the group who did not use them. Conclusions  The
      present study found that there may be a relationship between hearing changes and
      hormonal fluctuations during the menstrual cycle based on changes in the hearing
      thresholds of women. In addition, this study suggests that estrogen has an
      otoprotective effect on hearing, since the best hearing thresholds were found
      when estrogen was at its maximum peak.

PMID- 29018494
TI  - Evaluation of the Efficacy and Tolerability of Oral Ciprofloxacin used in the
      Comprehensive Treatment of External Bacterial Otitis: An Observational
      Prospective Study.
AB  - Introduction  Otitis Externa is common ear infection with a prevalence of 1%.
      Objective  The objective of this study is to evaluate the clinical and
      microbiological efficacy and safety profile with oral ciprofloxacin in the
      external bacterial otitis (EBO) management. Methods  This is a prospective
      observational study conducted with EBO outpatients referred to the
      otorhinolaryngology center in Moscow between March and August 2013. Our study
      included patients from two cohorts, acute external bacterial otitis (AEBO) -
      Group 1 - and exacerbation of chronic otitis externa (CEBO) - Group 2. We
      administered Ciprofloxacin 500 mg twice daily with standard topical EBO treatment
      for up to 10 days. Patients underwent evaluation on study visit days 1, 3, 5, and
      10 for the severity. Bacteriological examination of ear canal cultures took place
      on Day 1 and Day 10. Results  We collected data from 60 EBO outpatients (AEBO: N 
      = 30 and CEBO: N  = 30). Swimming was the major risk factor associated with the
      disease in addition to the most common pathogenic organisms - Staphylococcus
      aureus and Pseudomonas aeruginosa . was We attained complete resolution of the
      inflammatory process in 28 (93%) and 27 (90%) patients in the AEBO and CEBO
      group, respectively. We confirmed this by microbiological test with almost
      complete eradication of the causative organisms. Overall, we observed good
      positive dynamics of ear canal with no major side effects. Conclusion  We found
      that Ciprofloxacin 500 mg, when administered orally twice daily for 7 to 10 days
      in otitis externa patients is clinically and microbiologically effective and
      comparatively safer than other antimicrobials.

PMID- 29018495
TI  - Frequency Dependence Hearing Loss Evaluation in Perforated Tympanic Membrane.
AB  - Introduction  Tympanic membrane perforation is a relatively common problem that
      predisposes patients to varying degrees of conductive hearing loss. Objective 
      The objective of this study is to evaluate and analyze the frequency dependence
      hearing loss in tympanic membrane perforation based on the size and the site of
      perforation. Methods  For the study, I selected 71 patients' (89) ears for the
      cross-sectional study with tympanic membrane perforations; I examined the size
      and the site of perforations under the microscope and classified them into small,
      moderate, large, and subtotal perforations, and into anterior central, posterior
      central, malleolor central, and big central perforations. I measured mean level
      of speech frequencies hearing loss, and its relation with the site and the size
      of the perforation analyzed. Results  The mean hearing loss at different sizes of
      the perforation at all speech frequencies was 37.4 dB, with ABG of 26.6 dB, and
      its maximum loss was detected in subtotal perforation of 42.3 dB, with ABG of
      33.7 dB, at 500 Hz frequency, while in relation to the sites, it was 38.2 dB,
      with ABG of 26.8 dB, and its maximum loss was detected in big central site
      perforation of 42.1 dB, with ABG of 33.6 dB, at 500 Hz frequency. Conclusions 
      The hearing loss was proportionally related with the sizes of the perforations,
      and the posterior site had greater impact on the hearing than anterior site
      perforations. This was also applied to the frequency dependence hearing level, as
      was detected to be worse at lower frequencies as 500 Hz, than those of 1000-2000
      Hz.

PMID- 29018496
TI  - Surgical Treatment of Acquired Atresia of the External Auditory Ear Canal.
AB  - Introduction  Acquired atresia of the external auditory canal is characterized by
      the formation of fibrous tissue in the medial part. The causes include chronic
      otitis externa, perforated chronic otitis media, postoperative or idiopathic
      healing problems. Acquired atresia presents with hearing loss and can be
      associated with otorrhea. Objective  We analyzed the results of surgery after six
      months and two years by checking (1) pre- and postoperative hearing thresholds;
      (2) presence of otorrhea; and (3) whether a dry and patent ear canal is achieved.
      Methods  We conducted this retrospective study at a tertiary referral center. In
      total, 27 ears underwent treatment with resection of the fibrotic plug followed
      by transplantation of a split-thickness skin graft covering the bare bone and
      tympanic membrane. When necessary, we combined this with a myringoplasty and a
      (meato-) canalplasty. Results  Otorrhea was present in 59.3% of the patients
      initially and in 14.8% at six months and 11% at two years postoperative. A dry
      and patent ear canal was obtained in 55.6% after six months and in 89% of the
      patients after two years ( n  = 27). The pure tone average before surgery was
      39.1 dBHL (SD = 20 dBHL), at six months 31.4 dBHL (SD = 16.4 dBHL), and at 24
      months postop 30.9 dBHL (SD = 17.1 dBHL). We observed a statistically significant
      improvement of hearing in 63% of the patients at six months ( p  = 0.005) and in
      65% after two years ( p  = 0.022). Conclusions  Treatment of acquired atresia
      remains a challenge. Using the appropriate surgical technique, including skin
      grafting and regular postoperative check-up, rendered excellent results regarding
      otorrhea and a moderate improvement of hearing was achieved in 65% of the
      patients after two years.

PMID- 29018497
TI  - P300: Waves Identification with and without Subtraction of Traces.
AB  - Introduction  The P300 test requires well-defined and unique criteria, in
      addition to training for the examiners, for a uniform analysis of studies and to
      avoid variations and errors in the interpretation of measurement results.
      Objectives  The objective of this study is to verify whether there are
      differences in P300 with and without subtraction of traces of standard and
      nonstandard stimuli. Method  We conducted this study in collaboration with two
      research electrophysiology laboratories. From Laboratory 1, we selected 40 tests
      of subjects between 7-44 years, from Laboratory 2, we selected 83 tests of
      subjects between 18-44 years. We first performed the identification with the
      nonstandard stimuli; then, we subtracted the nonstandard stimuli from the
      standard stimuli. The examiners identified the waves, performing a descriptive
      and comparative analysis of traces with and without subtraction. Results  After a
      comparative analysis of the traces with and without subtraction, there was no
      significant difference when compared with analysis of traces in both
      laboratories, within the conditions, of right ears ( p  = 0.13 and 0.28 for
      differences between latency and amplitude measurements) and left ears ( p  = 0.15
      and 0.09 for differences between latency and amplitude measurements) from
      Laboratory 1. As for Laboratory 2, when investigating both ears, results did not
      identify significant differences ( p  = 0.098 and 0.28 for differences between
      latency and amplitude measurements). Conclusion  There was no difference verified
      in traces with and without subtraction. We suggest the identification of this
      potential performed through nonstandard stimuli.

PMID- 29018498
TI  - Cortical Auditory Evoked Potentials with Simple (Tone Burst) and Complex (Speech)
      Stimuli in Children with Cochlear Implant.
AB  - Introduction  The registry of the component P1 of the cortical auditory evoked
      potential has been widely used to analyze the behavior of auditory pathways in
      response to cochlear implant stimulation. Objective  To determine the influence
      of aural rehabilitation in the parameters of latency and amplitude of the P1
      cortical auditory evoked potential component elicited by simple auditory stimuli
      (tone burst) and complex stimuli (speech) in children with cochlear implants.
      Method  The study included six individuals of both genders aged 5 to 10 years old
      who have been cochlear implant users for at least 12 months, and who attended
      auditory rehabilitation with an aural rehabilitation therapy approach.
      Participants were submitted to research of the cortical auditory evoked potential
      at the beginning of the study and after 3 months of aural rehabilitation. To
      elicit the responses, simple stimuli (tone burst) and complex stimuli (speech)
      were used and presented in free field at 70 dB HL. The results were statistically
      analyzed, and both evaluations were compared. Results  There was no significant
      difference between the type of eliciting stimulus of the cortical auditory evoked
      potential for the latency and the amplitude of P1. There was a statistically
      significant difference in the P1 latency between the evaluations for both
      stimuli, with reduction of the latency in the second evaluation after 3 months of
      auditory rehabilitation. There was no statistically significant difference
      regarding the amplitude of P1 under the two types of stimuli or in the two
      evaluations. Conclusion  A decrease in latency of the P1 component elicited by
      both simple and complex stimuli was observed within a three-month interval in
      children with cochlear implant undergoing aural rehabilitation.

PMID- 29018499
TI  - Differentiating Benign from Malignant Sinonasal Lesions: Feasibility of Diffusion
      Weighted MRI.
AB  - Introduction  Appearance of nasal masses on routine CT and MRI are not
      pathognomonic. We utilized the apparent diffusion coefficient (ADC) value
      obtained from diffusion weighted image (DWI) to detect the differences in the
      microstructures of tumor and non-tumor tissues. Objective  The objective of our
      study was to evaluate the diagnostic role of DWI and ADC values in
      differentiating between malignant and benign sinonasal lesions and its
      correlation with histopathological results as the reference standard. Methods 
      Patients with nasal and / or paranasal mass underwent CT, MRI, and DWI before any
      surgical intervention. We used diagnostic sinonasal endoscopy and biopsy to
      confirm the diagnosis after MRI. Results  When we used ADC value of (1.2 * 10-3
      mm2/s) as a cut-off value for differentiating benign from malignant sinonasal
      lesions, we achieved 90% accuracy, 100% sensitivity, 88.4% specificity, 77.8%
      positive predictive value, and 100% negative predictive value. At this cut-off,
      benign lesions show statistically significant higher ADC value than malignant
      tumors. Conclusion  DW MRI and ADC value calculation are promising quantitative
      methods helping to differentiate between malignant and benign sinonasal lesions.
      Thus, they are effective methods compared with other conventional methods with
      short imaging time thus it is recommended to be incorporated into routine
      evaluations.

PMID- 29018500
TI  - Computed Tomography Measurement of Inferior Turbinate in Asymptomatic Adult.
AB  - Introduction  The inferior turbinate (IT) is the most susceptible turbinate to
      enlargement causing nasal obstruction. The common belief ascribes most of the
      enlargement of the IT to mucosal elements. Objective  This study aimed to
      investigate the detailed computed tomography (CT) measurement of the IT in
      asymptomatic adult by determining the thickness of both the non-bony (mucosa) and
      bony parts and their relation to nasal air space in different related areas of
      the nose. Methods  We included in the study paranasal CT scans of 108 individuals
      (216 IT) that had no paranasal pathology. We acquired axial images with
      multiplanar reformates to obtain delicate details in coronal and sagittal planes
      for all subjects. We took separate measurements of the thickness of the medial
      mucosa, bones, and lateral mucosa of the IT on the anterior and posterior
      portions of ITs. We also measured the air space of the nasal cavity between the
      septum and IT anteriorly and posteriorly. Results  The difference in the air
      space between nasal septum, anterior and posterior ends of IT was extremely
      statistically significant (P < 0.0001). The thickness of the medial mucosa was
      extremely significantly more than the lateral mucosa width (P < 0.0001). There
      was no significant difference in length of IT at both sides ( p  = 0.5781).
      Conclusion  The detailed CT measurement of the IT in normal adult is an easy and
      novel measurement. This study lays the foundation for CT measurement of IT for
      further work that can describe changes in IT measures after turbinate surgery.

PMID- 29018501
TI  - Quality of Life in Pediatric Patients with Allergic Rhinitis treated at the
      Medical Clinic of Integrated Education - Unisul.
AB  - Introduction  Allergic rhinitis is a common disease among children and
      adolescents, reaching up to 40% of the population. During childhood, it is
      usually underdiagnosed because it has nonspecific symptoms. It has a negative
      impact on quality of life and may predispose to comorbidities. The diagnosis is
      clinical and treatment aims prevention. Objective  The objective of this study is
      to evaluate the quality of life in pediatric patients with allergic rhinitis.
      Methods This is an observational study with cross-sectional design. The
      population consisted of pediatric patients with allergic rhinitis treated at the
      Medical Clinic of Integrated Education (MCIE) - Universidade do Sul de Santa
      Catarina - Unisul, Tubarao, SC, Brazil. We collected data from March to June 2016
      through the application of the Sociodemographic and Health Questionnaire,
      rhinitis module of the International Study of Asthma and Allergies in Childhood
      Questionnaire and the Rhinoconjunctivitis Quality of Life Questionnaire Modified.
      Results  Out of the 69 respondents, 52.2% were boys with a mean age of 10.13
      years old. The predominant education level of parents/guardians was incomplete
      second grade and average income level was two minimum wages. 81.2% said they had
      previous treatment for AR, 30.4% had asthma and 7.2% eczema. Incidence of
      patients smoking was absent and family (parents/guardians) smoking was 17.4%.
      March to July were the months of highest symptom occurrence, slightly disturbing
      daily activities. The mean value of severity was 51.9, nasal symptoms were the
      most uncomfortable, and nasal itchiness was the most cited. Conclusion  Our
      results highlight that allergic symptoms negatively impact the life of people
      with allergic rhinitis, with a predominance of nasal symptoms, especially nasal
      itchy, representing a poor quality of life of the interviewed.

PMID- 29018502
TI  - Persistent Tracheostomy after Organ Preservation Protocol in Patients Treated for
      Larynx and Hypopharynx Cancer.
AB  - Introduction  Squamous cell carcinoma of the larynx is currently the second most
      common malignancy of the airway after lung cancer, and hypopharyngeal cancer
      accounts for fewer than 5% of head and neck cancers. The nonsurgical options for
      patients with this disease are related to significant long-term toxicities and
      the need for persistent tracheostomy, which adversely affects the quality of life
      of these patients. Objective  To evaluate the need for tracheostomy, and the
      influence of this in the overall and specific survival rates of patients
      diagnosed with all stages of laryngeal carcinoma treated by chemoradiotherapy.
      Methods  A retrospective study of patients diagnosed with laryngeal carcinoma was
      performed according to the criteria of the Union for International Cancer Control
      (UICC) and the American Joint Committee on Cancer (AJCC) 7th edition, in a
      tertiary hospital. Results  A total of 21 patients were evaluated, 8 patients
      required a tracheotomy (31%) during the treatment protocol, 7 (35%) men and 1
      (100%) women. According to subsite 4/4 patient with glottis cancer (p <= 0.001),
      2/10 patients with supra glottis cancer and 2/7 patients with hypopharyngeal
      cancer. During follow up, just in 1 patient was possible to close the
      tracheostomy. Conclusion  Persistent tracheostomy dependence after primary
      chemoradiation increases significantly the morbidity, and decreases the quality
      of life of those patients. Patients with glottis cancer are prone to need a
      tracheostomy, but no statistical difference regarding the oncological stage and
      the need for a tracheostomy were detected. A more thorough selection of the
      patients is needed to improve the quality of life and reduce permanent
      tracheostomy dependence.

PMID- 29018503
TI  - Parameters Influencing Tracheostomy Decannulation in Patients Undergoing
      Rehabilitation after severe Acquired Brain Injury (sABI).
AB  - Introduction  Tracheostomy weaning in patients who suffered a severe acquired
      brain injury is often a challenge and decannulation failures are not uncommon.
      Objective  Our study objective is to describe the decannulation failure rate in
      patients undergoing rehabilitation following a severe acquired brain injury
      (sABI); to describe the factors associated with a successful tube weaning.
      Methods  We conduct a retrospective analysis of charts, consecutively retrieved
      considering a 3-year window. Variables analyzed were: age, sex, body mass index
      (BMI), Glasgow Coma Scale (GCS), cause of hospitalization (stroke, trauma,
      cardiac arrest), date of the pathological event, gap between the index event and
      the first day of hospitalization, duration of Neurorehabilitation Ward
      hospitalization, comorbidities, chest morphological alteration, kind of
      tracheostomy tube used (overall dimension, cap, fenestration), SpO2, presentation
      and quantification of pulmonary secretion, maximal inspiratory pressure (MIP) and
      maximal expiratory pressure (MEP), respiratory frequency and pattern, cardiac
      frequency, presence of spontaneous cough, cough strength, and blood gas analysis.
      Results  We analyzed 45 tracheostomised sABI patients following stroke, trauma,
      or cardiac arrest. The weaning success percentage was higher in Head Trauma
      patients and in patients presenting positive spontaneous cough. Failures seem to
      be associated with presence of secretions and anoxic brain damage. GCS seemed not
      related to the decannulation outcome. Conclusions  Parameters that could be used
      as positive predictors of weaning are: mean expiratory pressure, presence of
      spontaneous cough, and cough strength. Provoked cough and GCS were not predictive
      of weaning success.

PMID- 29018504
TI  - HMGB1 in the Pathogenesis of Nasal Inflammatory Diseases and its Inhibition as
      New Therapeutic Approach: A Review from the Literature.
AB  - Introduction  This study is a systematic review on recent developments about the
      importance of HMGB1 protein in the pathogenesis of rhino-sinusal inflammatory
      diseases. We also report data on the use of 18-beta-glycyrrhetic acid (GA), which
      has been shown able to inhibit the pro-inflammatory activities of HMGB1, in young
      patients affected by allergic rhinitis and complaining of nasal obstruction as
      main symptom. Objectives  The objective of this study was to review the
      literature to demonstrate the importance of HMGB1 in the pathogenesis of nasal
      inflammatory disorders and understand whether the inhibition of this protein may
      be an efficacious and innovative therapeutic strategy for patients with rhino
      sinusal inflammation. Data Synthesis  Authors searched for pertinent articles
      indexed in PubMed, Scopus, and other health journals between 2004 and 2015. In
      total, the authors gathered 258 articles: 219 articles through Pubmed and 39
      articles from other search engines. The search terms used were as follows: HMGB1
      AND "respiratory epithelium," "airway inflammation," "rhinitis," "allergic
      rhinitis," "rhinosinusitis," "nasal polyposis," "glycyrrhetic acid," "children."
      Conclusions  Patients with severe symptoms have the highest serum levels and the
      highest extracellular expression of HMGB1. GA inhibits HMGB1 chemotactic and
      mitogenic function by a scavenger mechanism on extracellular HMGB1 accumulation
      stimulated by lipopolysaccharides in vitro. Treatment of allergic rhinitis with
      GA is not associated with local or systemic side effects in children and adults.

PMID- 29018506
TI  - Clinical Features and Surgical Treatment of Schwannoma Affecting the Base of the
      Tongue: A Systematic Review.
AB  - Introduction  Schwannomas of the head and neck account for 25-40% of all cases,
      with presentation at the base of the tongue as the most frequent site for
      intraoral tumors. Objectives  Here, a systematic review was conducted to include
      15 cases of patients with schwannoma of the base of the tongue. Data Synthesis 
      Most patients presented with a single, painless, well-encapsulated nodule at the
      base of the tongue. These nodules were slow-growing, with an average of 13.3
      months from onset to presentation. Most cases were accompanied by airway
      obstruction, indicated by symptoms of dysphagia, dysarthria, snoring, and sleep
      apnea. Overall, the histological studies were consistent with a benign schwannoma
      with a palisading Antoni A and Antoni B pattern without malignant changes in cell
      morphology. These tumors were treated via complete surgical excision, and all
      cases achieved full remission by final follow-up. Conclusion  Surgical removal is
      the primary mode of treatment with excellent postoperative prognosis and rare
      instances of recurrence. Given the rarity of this tumor, this review of available
      case studies serves to comprehensively describe clinical presentation and
      surgical treatment approaches to tongue base schwannoma.

PMID- 29018505
TI  - Head and Neck Lymphomas in HIV Patients: a Clinical Perspective.
AB  - Introduction  Because of the many HIV-related malignancies, the diagnosis and
      treatment of lymphoma in patients infected with human immunodeficiency virus are
      challenging. Objective  Here, we review current knowledge of the pathogenesis,
      epidemiology, symptomatology, diagnosis, and treatment of head and neck lymphomas
      in HIV patients from a clinical perspective. Data Synthesis  Although Hodgkin's
      lymphoma is not an AIDS-defining neoplasm, its prevalence is ten times higher in
      HIV patients than in the general population. NHL is the second most common
      malignancy in HIV patients, after Kaposi's sarcoma. In this group of patients,
      NHL is characterized by rapid progression, frequent extranodal involvement, and a
      poor outcome. HIV-related salivary gland disease is a benign condition that
      shares some features with lymphomas and is considered in their differential
      diagnosis. Conclusion  The otolaryngologist may be the first clinician to
      diagnose head and neck lymphomas. The increasing survival of HIV patients implies
      clinical and epidemiological changes in the behavior of this disease. Early
      diagnosis is important to improve the prognosis and avoid the propagation of HIV
      infection.

PMID- 29018508
TI  - Gait Improvements After Peroneal or Tibial Nerve Transfer in Patients with Foot
      Drop: A Retrospective Study.
AB  - Background: Injury to the common peroneal nerve disrupts the motor control
      pathway to ankle dorsiflexors and evertors, as well as toe extensors, resulting
      in pathological gait and foot drop. Direct external compression on the fibular
      head is the most frequent cause of peroneal nerve impairment and has poor
      prognosis. Methods and Patients: Here, we report the surgical outcome of 21
      patients with foot drop (9 males and 12 females) who underwent nerve transfer
      procedure of either the superficial peroneal nerve or the tibial nerve fascicles
      to the motor branch of the tibialis anterior and to the deep peroneal nerve. They
      had at least 6 months postoperative follow-up (mean = 17; range, 6-32 months).
      Results: Among 21 patients who had no ankle dorsiflexion (BMRC 0/5)
      preoperatively, 9 patients had successful restoration of ankle dorsiflexion (BMRC
      4 to 4+/5), 7 patients had BMRC 2 to 3+/5, and 4 patients had no or poor
      restoration of dorsiflexion (BMRC 0 to 1+/5) but achieved good ankle eversion
      (BMRC 3 to 4+/5). Overall statistically significant clinical improvement of ankle
      dorsiflexion and eversion from preoperative BMRC grade 2.6 +/- 0.5 to
      postoperative BMRC grade 3.6 +/- 0.7 (P = .0000004) was achieved. Conclusion:
      Overall statistically significant clinical improvement of ankle dorsiflexion and
      eversion was achieved in 80% of our study patients. Most of these patients gained
      antigravity and were able to walk with minimal steppage gait. In the other 4
      patients (20%), there was good improvement in ankle eversion but poor or no ankle
      dorsiflexion.

PMID- 29018507
TI  - Down-regulation of MBD4 contributes to hypomethylation and overexpression of CD70
      in CD4+ T cells in systemic lupus erythematosus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease that is
      characterized by lymphocytic infiltration and overproduction of autoantibodies,
      leading to significant morbidity and mortality. However, the pathogenesis of this
      disorder has not yet been completely elucidated. It has been reported that CD70,
      a B cell costimulatory molecule encoded by the gene TNFSF7 (tumor necrosis factor
      ligand superfamily member 7), is overexpressed in CD4+ T cells from patients with
      SLE due to the demethylation of its promoter. We aimed to investigate the
      expression patterns of MBD4 (methyl-CpG binding domain protein 4) in CD4+ T cells
      and its contribution to the pathogenesis of SLE by increasing CD70 expression
      through epigenetic regulation. RESULTS: Our results showed that the expression of
      MBD4 was significantly decreased in CD4+ T cells from SLE patients. We verified
      that transfection of MBD4 siRNA into healthy CD4+ T cells upregulated expression
      of CD70 and decreased the methylation level of the CD70 promoter. Overexpression
      of MBD4 inhibited CD70 expression and enhanced the DNA methylation level of CD70
      in CD4+ T cells of SLE patients. CONCLUSION: Our results indicated that
      downregulation of MBD4 contributed to overexpression and hypomethylation of the
      CD70 gene in SLE CD4+ T cells. This modulation of MBD4 may provide a novel
      therapeutic approach for SLE.

PMID- 29018510
TI  - ROS and Oxidative Stress in Stem Cells.

PMID- 29018509
TI  - circRNA_0046367 Prevents Hepatoxicity of Lipid Peroxidation: An Inhibitory Role
      against Hepatic Steatosis.
AB  - Hepatic steatosis reflects the miRNA-related pathological disorder with
      triglyceride accumulation and lipid peroxidation, which leads to nonalcoholic
      steatohepatitis, liver fibrosis/cirrhosis, and even hepatocellular carcinoma.
      Circular RNA (circRNA)/miRNA interaction reveals a novel layer of epigenetic
      regulation, yet the miRNA-targeting circRNA remains uncertain in hepatic
      steatosis. Here, we uncover circRNA_0046367 to be endogenous modulator of miR-34a
      that underlies hepatic steatosis. In contrast to its expression loss during the
      hepatocellular steatosis in vivo and in vitro, circRNA_0046367 normalization
      abolished miR-34a's inhibitory effect on peroxisome proliferator-activated
      receptor alpha (PPARalpha) via blocking the miRNA/mRNA interaction with miRNA
      response elements (MREs). PPARalpha restoration led to the transcriptional
      activation of genes associated with lipid metabolism, including carnitine
      palmitoyltransferase 2 (CPT2) and acyl-CoA binding domain containing 3 (ACBD3),
      and then resulted in the steatosis resolution. Hepatotoxicity of steatosis
      related lipid peroxidation, being characterized by mitochondrial dysfunction,
      growth arrest, and apoptosis, is resultantly prevented after the circRNA_0046367
      administration. These findings indicate a circRNA_0046367/miR-34a/PPARalpha
      regulatory system underlying hepatic steatosis. Normalized expression of
      circRNA_0046367 may ameliorate the lipoxidative stress on the basis of steatosis
      attenuation. circRNA_0046367, therefore, is suggested to be potential approach to
      the therapy of lipid peroxidative damage.

PMID- 29018512
TI  - Time for Practical Clinical Tools.

PMID- 29018513
TI  - Effective Patient Care in a Data-Driven World.

PMID- 29018511
TI  - Neurocognitive and observational markers: prediction of autism spectrum disorder
      from infancy to mid-childhood.
AB  - BACKGROUND: Prospective studies of infants at high familial risk for autism
      spectrum disorder (ASD) have identified a number of putative early markers that
      are associated with ASD outcome at 3 years of age. However, some diagnostic
      changes occur between toddlerhood and mid-childhood, which raises the question of
      whether infant markers remain associated with diagnosis into mid-childhood.
      METHODS: First, we tested whether infant neurocognitive markers (7-month neural
      response to eye gaze shifts and 14-month visual disengagement latencies) as well
      as an observational marker of emerging ASD behaviours (the Autism Observation
      Scale for Infants; AOSI) predicted ASD outcome in high-risk (HR) 7-year-olds with
      and without an ASD diagnosis (HR-ASD and HR-No ASD) and low risk (LR) controls.
      Second, we tested whether the neurocognitive markers offer predictive power over
      and above the AOSI. RESULTS: Both neurocognitive markers distinguished children
      with an ASD diagnosis at 7 years of age from those in the HR-No ASD and LR
      groups. Exploratory analysis suggested that neurocognitive markers may further
      differentiate stable versus lost/late diagnosis across the 3 to 7 year period,
      which will need to be tested in larger samples. At both 7 and 14 months,
      combining the neurocognitive marker with the AOSI offered a significantly
      improved model fit over the AOSI alone. CONCLUSIONS: Infant neurocognitive
      markers relate to ASD in mid-childhood, improving predictive power over and above
      an early observational marker. The findings have implications for understanding
      the neurodevelopmental mechanisms that lead from risk to disorder and for
      identification of potential targets of pre-emptive intervention.

PMID- 29018515
TI  - Letter from the New President of the European Heart Rhythm Association.

PMID- 29018514
TI  - A Future Perspective on the Europace Journal: its Star is Rising.

PMID- 29018516
TI  - Is There a Future for Remote Cardiac Implantable Electronic Device Management?
AB  - In the era of communication technology, remote monitoring has been a paradigm
      shift in the way patients with cardiac implantable electronic devices are
      managed. It has been endorsed by scientific societies and is being increasingly
      adopted in the clinical setting. Despite the various advantages associated with
      this strategy, data on improved clinical outcome are still sparse. The recently
      published study on the remote management of heart failure using implanted devices
      and formalised follow-up procedures, which turned out to be negative, has cast
      doubt on whether remote monitoring should still be used. This article provides a
      critical appraisal of the study, and discusses the issue of remote data
      management.

PMID- 29018517
TI  - Key Lessons from the ELECTRa Registry in the Modern Era of Transvenous Lead
      Extraction.
AB  - The implantation rate of cardiac electronic devices has grown over the past
      decades. The number of treated patients has increased in parallel with the
      complexity of the patient population treated, being older, frailer, having more
      complex devices (in particular, cardiac resynchronisation therapy) and presenting
      with a greater comorbidity burden. As a consequence, there is a rising number of
      related implanted system complications, including malfunction and infection.
      Thus, the demand for transvenous lead extraction (TLE) has also substantially
      increased. To identify the indication to TLE by various operators and centres,
      techniques used to perform TLE, and the safety and efficacy of the current
      clinical practice of TLE, a large prospective registry has been started in Europe
      - the European Lead Extraction Controlled (ELECTRa) Registry. The key findings of
      the ELECTRa Registry are discussed in the present review and placed in the
      context of previous knowledge. The ELECTRa Registry confirms that the TLE
      procedure is a safe and effective treatment, with an acceptable risk-benefit
      ratio that is comparable with other well-known cardiological invasive procedures.
      Of course, TLE is accompanied by potential life-threatening complications; the
      vast majority of these can be managed by an experienced multidisciplinary team.
      Multiple factors predict complications, including patient/lead profile, centre
      experience and procedure volumes, which may suggest caution when accepting a
      patient for TLE.

PMID- 29018518
TI  - Cardiac Effects of Lightning Strikes.
AB  - Lightning strikes are a common and leading cause of morbidity and mortality.
      Multiple organ systems can be involved, though the effects of the electrical
      current on the cardiovascular system are one of the main modes leading to
      cardiorespiratory arrest in these patients. Cardiac effects of lightning strikes
      can be transient or persistent, and include benign or life-threatening
      arrhythmias, inappropriate therapies from cardiac implantable electronic devices,
      cardiac ischaemia, myocardial contusion, pericardial disease, aortic injury, as
      well as cardiomyopathy with associated ventricular failure. Prolonged
      resuscitation can lead to favourable outcomes especially in young and previously
      healthy victims.

PMID- 29018521
TI  - End-of-life Management of Leadless Cardiac Pacemaker Therapy.
AB  - The clinically available leadless pacemakers for patients with a single-chamber
      pacing indication have shown to be safe and effective. However, the optimal end
      of-life strategy of this novel technique is undefined. Suggested strategies
      comprise of (a) placing an additional leadless device adjacent to the leadless
      pacemaker, or (b) retrieving the non-functioning leadless pacemaker and
      subsequently implanting a new device. Although initial studies demonstrate
      promising results, early experience of acute and mid-term retrieval feasibility
      and safety remains mixed. We suggest that the approach of leadless pacemaker
      retrieval is more appealing to limit the amount of non-functioning intracardiac
      hardware. In addition, potential risks for device-device interference, and
      unknown long-term complications associated with multiple intracardiac devices are
      prevented. The potential inability to retrieve chronically implanted leadless
      pacemakers limits the application of this novel technology. Therefore, long-term
      prospective analysis is required to define the most optimal end-of-life strategy.

PMID- 29018520
TI  - Prophylactic Catheter Ablation for Ventricular Tachycardia: Are We There Yet?
AB  - Ventricular tachycardia (VT), often degenerating into ventricular fibrillation,
      is the leading cause of sudden cardiac death. Catheter ablation of VT is
      associated with relatively low, long-term success rates, while the optimal timing
      of ablation in patients with ischaemic and non-ischaemic cardiomyopathy remains
      unclear. Contemporary practice in most centres is to consider ablation late in
      the disease process following the failure of anti-arrhythmic medications and/or
      following recurrent implantable cardioverter-defibrillator shocks. Three major
      randomised, controlled trials have been published investigating the role of
      prophylactic catheter ablation for VT. In the present review, we assess the
      evidence from these and other related trials in VT ablation to understand if
      there is sufficient evidence to advocate prophylactic catheter ablation in
      patients with VT.

PMID- 29018522
TI  - Ventricular Arrhythmia after Acute Myocardial Infarction: 'The Perfect Storm'.
AB  - Ventricular tachyarrhythmias (VAs) commonly occur early in ischaemia, and remain
      a common cause of sudden death in acute MI. The thrombolysis and primary
      percutaneous coronary intervention era has resulted in the modification of the
      natural history of an infarct and subsequent VA. Presence of VA could
      independently influence mortality in patients recovering from MI. Appropriate
      risk assessment and subsequent treatment is warranted in these patients. The
      prevention and treatment of haemodynamically significant VA in the post-infarct
      period and of sudden cardiac death remote from the event remain areas of ongoing
      study.

PMID- 29018523
TI  - Comparative study of two protocols for quantitative image-analysis of serotonin
      transporter clustering in lymphocytes, a putative biomarker of therapeutic
      efficacy in major depression.
AB  - BACKGROUND: The pattern of serotonin transporter clustering on the plasma
      membrane of lymphocytes extracted from human whole blood samples has been
      identified as a putative biomarker of therapeutic efficacy in major depression.
      Here we evaluated the possibility of performing a similar analysis using blood
      smears obtained from rats, and from control human subjects and depression
      patients. We hypothesized that we could optimize a protocol to make the analysis
      of serotonin protein clustering in blood smears comparable to the analysis of
      serotonin protein clustering using isolated lymphocytes. RESULTS: Our data
      indicate that blood smears require a longer fixation time and longer times of
      incubation with primary and secondary antibodies. In addition, one needs to
      optimize the image analysis settings for the analysis of smears. When these steps
      are followed, the quantitative analysis of both the number and size of serotonin
      transporter clusters on the plasma membrane of lymphocytes is similar using both
      blood smears and isolated lymphocytes. CONCLUSIONS: The development of this novel
      protocol will greatly facilitate the collection of appropriate samples by
      eliminating the necessity and cost of specialized personnel for drawing blood
      samples, and by being a less invasive procedure. Therefore, this protocol will
      help us advance the validation of membrane protein clustering in lymphocytes as a
      biomarker of therapeutic efficacy in major depression, and bring it closer to its
      clinical application.

PMID- 29018519
TI  - Limitations and Challenges in Mapping Ventricular Tachycardia: New Technologies
      and Future Directions.
AB  - Recurrent episodes of ventricular tachycardia in patients with structural heart
      disease are associated with increased mortality and morbidity, despite the life
      saving benefits of implantable cardiac defibrillators. Reducing implantable
      cardiac defibrillator therapies is important, as recurrent shocks can cause
      increased myocardial damage and stunning, despite the conversion of ventricular
      tachycardia/ventricular fibrillation. Catheter ablation has emerged as a
      potential therapeutic option either for primary or secondary prevention of these
      arrhythmias, particularly in post-myocardial infarction cases where the substrate
      is well defined. However, the outcomes of catheter ablation of ventricular
      tachycardia in structural heart disease remain unsatisfactory in comparison with
      other electrophysiological procedures. The disappointing efficacy of ventricular
      tachycardia ablation in structural heart disease is multifactorial. In this
      review, we discuss the issues surrounding this and examine the limitations of
      current mapping approaches, as well as newer technologies that might help address
      them.

PMID- 29018524
TI  - Re-evaluation of soluble APP-alpha and APP-beta in cerebrospinal fluid as
      potential biomarkers for early diagnosis of dementia disorders.
AB  - BACKGROUND: Because soluble (or secreted) amyloid precursor protein-beta
      (sAPPbeta) and -alpha (sAPPalpha) possibly reflect pathological features of
      Alzheimer's disease (AD), they are potential biomarker candidates for dementia
      disorders, including AD and mild cognitive impairment (MCI) due to AD (MCI-AD).
      However, controversial results have been reported regarding their alterations in
      the cerebrospinal fluid (CSF) of AD and MCI-AD patients. In this study, we re
      assessed the utility of sAPPalpha and sAPPbeta in CSF as diagnostic biomarkers of
      dementia disorders. METHODS: We used a modified and sensitive detection method to
      analyze sAPPs levels in CSF in four groups of patients: AD (N = 33), MCI-AD (N =
      17), non-AD dementia (N = 27), and disease controls (N = 19). Phosphorylated tau
      (p-tau), total tau, and Abeta42 were also analyzed using standard methods.
      RESULTS: A strong correlation was observed between sAPPalpha and sAPPbeta,
      consistent with previous reports. Both sAPPalpha and sAPPbeta were highly
      correlated with p-tau and total tau, suggesting that sAPPs possibly reflect
      neuropathological changes in the brain. Levels of sAPPalpha were significantly
      higher in MCI-AD cases compared with non-AD and disease control cases, and those
      of sAPPbeta were also significantly higher in MCI-AD and AD cases relative to
      other cases. A logistic regression analysis indicated that sAPPalpha and sAPPbeta
      have good discriminative power for the diagnosis of MCI-AD. CONCLUSIONS: Our
      findings collectively suggest that both sAPPs are pathologically relevant and
      potentially useful biomarkers for early and accurate diagnosis of dementia
      disorders. We also suggest that careful measurement is important in assessing the
      diagnostic utility of CSF sAPPs.

PMID- 29018525
TI  - Concordance of opinions between patients and physicians and their relationship
      with symptomatic control and future risk in patients with moderate-severe asthma.
AB  - INTRODUCTION: Differences between the opinions of patients and physicians on the
      impact of asthma are common. We hypothesised that patient-physician discordance
      may negatively affect asthma outcome. METHODS: A total of 2902 patients (61%
      women, mean age 47 years) with moderate-severe asthma and 231 physicians
      participated in a prospective study. At the baseline visit, data on demographics,
      clinical variables, degree of asthma control according to the Asthma Control Test
      (ACT), basic spirometry and the Hospital Anxiety and Depression Scale (HADS) were
      collected and an ad hoc questionnaire was completed that allowed the degree of
      concordance between doctors and patients to be assessed. A scheduled telephone
      call after 3 months was used to elicit the ACT score and the future risk of
      asthma. At the final visit at 6 months, the following data were recorded: ACT
      score, spirometry, HADS score and an ad hoc questionnaire to assess the agreement
      between the doctor and the patient. Changes in study variables according to
      patient-physician concordance or discordance were analysed. RESULTS: The rate of
      patient-physician discordance was 27.2%, with overestimation of disease impact by
      the physician in 12.3% and underestimation in 14.9%. Patient-physician opinion
      discordance, particularly in the case of physicians underestimating the impact of
      asthma, showed worse results with statistically significant differences in ACT
      score, a higher percentage of patients with poor asthma control and lower HADS
      scores. The need for hospital and emergency department admissions was also
      higher. CONCLUSION: Patient-physician opinion discordance may be contributing to
      lower symptomatic control and increased future risk, with a higher impact when
      physicians underestimate the impact of asthma on their patients.

PMID- 29018528
TI  - Correction: Evaluation of the current landscape of respiratory nurse specialists
      in the UK: planning for the future needs of patients.
AB  - [This corrects the article DOI: 10.1136/bmjresp-2017-000210.][This corrects the
      article DOI: 10.1136/bmjresp-2017-000210.].

PMID- 29018527
TI  - British Thoracic Society quality standards for home oxygen use in adults.
AB  - INTRODUCTION: The purpose of the quality standards document is to provide
      healthcare professionals, commissioners, service providers and patients with a
      guide to standards of care that should be met for home oxygen provision in the
      UK, together with measurable markers of good practice. Quality statements are
      based on the British Thoracic Society (BTS) Guideline for Home Oxygen Use in
      Adults. METHODS: Development of BTS Quality Standards follows the BTS process of
      quality standard production based on the National Institute for Health and Care
      Excellence process manual for the development of quality standards. RESULTS: 10
      quality statements have been developed, each describing a key marker of high
      quality, cost-effective care for home oxygen use, and each statement is supported
      by quality measures that aim to improve the structure, process and outcomes of
      healthcare. DISCUSSION: BTS Quality Standards for home oxygen use in adults form
      a key part of the range of supporting materials that the society produces to
      assist in the dissemination and implementation of a guideline's recommendations.

PMID- 29018526
TI  - Design of the PF-ILD trial: a double-blind, randomised, placebo-controlled phase
      III trial of nintedanib in patients with progressive fibrosing interstitial lung
      disease.
AB  - : 600 patients aged >=18 years will be randomised in a 1:1 ratio to nintedanib or
      placebo. Patients with diagnosis of IPF will be excluded. The study population
      will be enriched with two-thirds having a usual interstitial pneumonia-like
      pattern on HRCT. The primary endpoint is the annual rate of decline in forced
      vital capacity over 52 weeks. The main secondary endpoints are the absolute
      change from baseline in King's Brief Interstitial Lung Disease Questionnaire
      total score, time to first acute interstitial lung disease exacerbation or death
      and time to all-cause mortality over 52 weeks. ETHICS AND DISSEMINATION: The
      trial is conducted in accordance with the Declaration of Helsinki, the
      International Conference on Harmonisation Tripartite Guideline for Good Clinical
      Practice (GCP) and Japanese GCP regulations. TRIAL REGISTRATION NUMBER:
      NCT02999178.

PMID- 29018529
TI  - Corrections: Glucose-lowering effect of whey protein depends upon clinical
      characteristics of patients with type 2 diabetes.
AB  - [This corrects the article DOI: 10.1136/bmjdrc-2017-000420.][This corrects the
      article DOI: 10.1136/bmjdrc-2017-000420.].

PMID- 29018530
TI  - Benchmarking welfare indicators in 73 free-stall dairy farms in north-western
      Spain.
AB  - The aim of this study was to describe the status of body condition score (BCS),
      hock injuries prevalence, locomotion and body hygiene score as animal welfare
      measures in 73 free-stall dairy cattle farms in Lugo (Spain). A benchmarking
      process was established across farms: (1) the animal-based indicators were
      ordered from low to high values; (2) The farms were classified into three
      categories based on the number of indicators within less than the 25th
      percentile, 25th to 75th percentile and above the 75th percentile. The median
      prevalence of unsuitable BCS, hock injuries and clinical lameness was (median
      (range)) 51.7 per cent (13.3 to 89.5 per cent), 40.0 per cent (7.0per cent to 100
      per cent) and 9.0 per cent (0per cent to 60.0 per cent) respectively. The
      dirtiness of the cow's coat had a high prevalence (73.0 per cent (37.5per cent to
      100 per cent)). Most farms did not display consistently good or poor animal-based
      indicators and each farm had its own set of strong and weak points. Moreover,
      facilities design and management practices were described to understand source of
      the observations made of the cows. The incidence of overstocking was 31.5 per
      cent for stalls and 26.0 per cent for headlocks. The front lunge space was
      reduced (<90 cm) on most dairies (90.4 per cent). Signs of poor natural
      ventilation (cobwebs or humidity on the roof) and ammonia odour were observed on
      32.8 per cent and 85.0 per cent of the barns totally closed or with a side
      openingless than 50 per cent of the wall height. The milking parlour was designed
      with two or more turns more than 90 degrees  (9.3 per cent), and failed to allow
      cows to see the parlour before entering (45.2 per cent). On 52.0 per cent of
      dairies, more than 15 per cent of the cows had to be forcefully moved into the
      milking parlour. In conclusion, there was a big variation in the animal welfare
      levels within and across farms and they could benefit from others by changing
      management practices related to facilities and herds.

PMID- 29018532
TI  - Real world data of a veterinary teaching hospital in Japan: a pilot survey of
      prescribed medicines.
AB  - The prescription data from a digital accounting system of a veterinary teaching
      hospital collected between 2008 and 2011 in Japan were downloaded, stored in a
      database and analysed using a statistical analysis software, SAS. Seventy-six per
      cent of all prescriptions were drugs approved for human beings. The most
      frequently prescribed category was 'Agents against pathogenic organisms', such as
      antibiotics and chemotherapeutic agents, followed by 'Cardiovascular agents'.
      Seventy-five per cent of prescribed oral formulations in the category 'Agents
      against pathogenic organisms' were drugs approved for human beings, while 78 per
      cent of the injectable prescriptions were those for veterinary. A total of 36
      oral antipathogenic products were prescribed, and among them amoxicillin was
      prescribed the most, followed by cephalexin for human beings and enrofloxacin for
      veterinary. The pattern of cyclosporin prescription, which is the most prescribed
      product other than 'Agents against pathogenic organisms', was surveyed. The
      capsule formulation was primarily used for dogs, while oral solutions were
      preferably used for cats. This pilot study is the first analytical data of real
      prescription in hospitals in Japan and one of the longest surveys in veterinary
      world.

PMID- 29018531
TI  - Magnetic resonance imaging to detect local tissue reactions after vaccination in
      sheep in vivo.
AB  - OBJECTIVES: Vaccination is one of the most effective methods to keep up the
      health status in humans and in livestock. Therefore, farm animals are vaccinated
      several times during their lifetime. Although vaccines are being checked
      regarding their local reactogenicity, side effects occur frequently-especially in
      the case of the application of adjuvanted products. Many reports exist about
      local reactions in sheep. The present study aimed at testing MRI as a method to
      document injection site reactions three-dimensionally. DESIGN: Two groups of
      Merino lambs (n=16 each) were vaccinated subcutaneously into the left neck side.
      Two different, licensed inactivated vaccines were used. Both groups of lambs were
      anaesthetised and scanned using MRI at days 1, 3, 8, 15, 22 and 29 after
      vaccination. SETTING: The study was performed on a commercial-like farm.
      PARTICIPANTS: Thirty-two Merino lambs entered the experiment, 16 male and 16
      female ones (one animal died at day 22 after vaccination). At first examination
      day they were approximately three months old. PRIMARY AND SECONDARY OUTCOME
      MEASURES: Volume differences were measured between vaccination and control neck
      side to evaluate the time pattern of local tissue reactions. RESULTS: Local
      tissue reactions were visible on the skin surface and also appeared in deeper
      tissue layers on MRI. These deeper reactions would not have been found without
      MRI or, alternatively, without sacrificing the animals. Some of these extensive
      local reactions lasted for more than 29 days. CONCLUSIONS: The in vivo MRI
      results proved suitable to record local tissue reactions in terms of three
      dimensional extent over a longer period of time in large farm animals without the
      need to sacrifice test animals. A three-dimensional MRI examination of the
      injection site during regulatory licensing studies offers an objective evaluation
      that could be used in a benefit-risk assessment of veterinary vaccines. TRIAL
      REGISTRATION NUMBER: District Government of Upper Bavaria:55.2-1-54-2532-2-13.

PMID- 29018534
TI  - Factors related to work and life satisfaction of veterinary practitioners in
      Germany.
AB  - OBJECTIVES: Veterinary practitioners' working situation is both challenging and
      changing. They have higher levels of work-related stress and suicide risk than
      the general population. The proportion of women is increasing, and in Germany
      especially women and employed veterinarians are reported to be less satisfied
      than comparable subgroups of the general population. In this study we identified
      key factors associated with work and life satisfaction among veterinary
      practitioners in Germany. DESIGN: Questionnaire-based cross-sectional survey.
      SETTING: All veterinary practitioners registered in Germany in 2016.
      PARTICIPANTS: There were 2549 respondents, of whom 1930 met the inclusion
      criteria for further analysis. They had a median age of 37 and the majority of
      respondents were women (79.3 per cent). Almost two-thirds (63.8 per cent) worked
      as employed veterinarian. PRIMARY OUTCOMES: Importance of different job
      characteristics measured in 5-point Likert items, work satisfaction measured on a
      5-point Likert item and life satisfaction measured in 11-point Likert items.
      SECONDARY OUTCOMES: Facets such as satisfaction with leisure time, family life,
      health and standard of living, information on working conditions such as working
      time, income, as well as year of birth and other demographic data. RESULTS: A
      'good working atmosphere' was the most relevant job characteristic for all
      veterinary practitioners. Work satisfaction of employed practitioners is closely
      linked to satisfaction with their colleagues. This link is less pronounced for
      self-employed practitioners. A 'reasonable salary' was the second and 'holidays
      and leisure time' was the third most important job characteristics for employed
      practitioners. A 'good working atmosphere' and 'family friendly arrangements'
      were statistically significantly more important for women than for men, while a
      'reasonable salary' was more important for men. CONCLUSIONS: Our results indicate
      strong associations between levels of work satisfaction and various work-related
      factors in subgroups of veterinary practitioners in Germany that reduce life
      satisfaction. The strength of some associations differs between men and women, as
      well as between self-employed and employed veterinarians. Outgoing students
      should be better prepared for the challenging working conditions that they face
      in veterinary practice. Salary levels should be improved and the working
      conditions adapted to the respective subgroups in order to increase work and life
      satisfaction.

PMID- 29018533
TI  - Pharmacokinetics of marbofloxacin administered via intravenous regional limb
      perfusion in dairy cows: evaluation of two different tourniquets.
AB  - OBJECTIVES: This study evaluated synovial and systemic plasma pharmacokinetic
      variables of marbofloxacin after a single intravenous regional limb perfusion
      (IVRLP) performed using two different tourniquets in clinically healthy,
      standing, non-sedated dairy cows. The authors hypothesised that the type of
      tourniquet used for IVRLP would influence the synovial fluid concentration of
      marbofloxacin in the perfused distal limb. DESIGN: The study had a randomised
      parallel-group design. METHODS: Ten adult dairy cows were included. Unilateral
      hindlimb IVRLP through the dorsal common digital III vein was performed in two
      groups of five cows (group 1: wide rubber tourniquet; group 2: manual pneumatic
      tourniquet) using 0.67 mg/kg of marbofloxacin. The tourniquet was applied
      proximal to the tarsus and maintained for 30 minutes. Samples of jugular blood
      and synovial fluid from the tibiotarsal joints of the perfused limb were obtained
      before and at intervals after IVRLP. All samples were analysed for drug
      concentrations using liquid chromatography tandem mass spectrometry.
      Pharmacokinetic parameters were determined to establish the influence of
      tourniquet types. Differences were considered significant at P<=0.05. RESULTS: No
      adverse effects from the procedure or marbofloxacin were observed in any animal.
      Significant differences in synovial concentrations and pharmacokinetic parameters
      were measured. The mean +/- sd areas under the concentration versus time curve
      from time 0 to 24 hours were 178.98+/-58.08 ug hour/ml for group 2 and 21.11+/
      9.93 ug hour/ml for group 1. The mean +/- sd maximum marbofloxacin concentrations
      were 75.50+/-10.19 ug/ml for group 2 and 6.35+/-1.47 ug/ml for group 1.
      CONCLUSIONS: Performing IVRLP using the dorsal common digital III vein and a
      manual pneumatic tourniquet set at 300 mmHg above the tarsus in standing cows
      resulted in significantly higher marbofloxacin concentrations in the tibiotarsal
      joint compared with those with the wide rubber tourniquet. TRIAL REGISTRATION:
      Local ethical committee (number 41/2012/CEISA).

PMID- 29018536
TI  - Efficacy and safety of non-vitamin K antagonist oral anticoagulants compared with
      warfarin in patients with atrial fibrillation.
AB  - AIMS: Non-vitamin K antagonist oral anticoagulants (NOACs) were in pivotal
      randomised controlled trials at least non-inferior to warfarin for stroke
      prevention in atrial fibrillation, but time in therapeutic range (TTR) for
      warfarin was lower (mean 55%-65%) than in Swedish general care where TTR is >70%.
      We compared efficacy and safety of NOACs and warfarin treatment for stroke
      prevention in Sweden. METHODS: Retrospective cohort study of all non-selected
      oral anticoagulation naive atrial fibrillation patients with first prescription
      for NOACs or warfarin between December 2011 and December 2014, excluding patients
      with mitral stenosis or mechanical valvular prosthesis. Data were obtained from
      cross-linked national registers, propensity scores were used as continuous
      covariates, and associations between treatment and outcomes were evaluated by
      multivariable Cox regressions. RESULTS: The study comprised 18 638 patients on
      NOAC and 49 418 on warfarin treatment, with 90 204 patient-years follow-up. Age
      (mean) was 73.4 vs 73.7 years, p<0.001, and CHA2DS2-VASc points (mean) 3.38 vs
      3.24, p<0.001, in NOAC and warfarin groups, respectively. HRs (95% CI) for NOACs
      versus warfarin were 1.04 (0.91-1.19) for all-cause stroke or systemic embolism,
      1.16 (1.00-1.35) for ischaemic stroke, 0.85 (0.76-0.96) for major bleeding, 1.22
      (1.01-1.46) for gastrointestinal bleeding, 0.60 (0.47-0.76) for intracranial
      haemorrhage and 0.89 (0.81-0.96) for all-cause mortality. CONCLUSION: In this
      large non-selected anticoagulation naive Swedish atrial fibrillation cohort, the
      risks for all-cause stroke or systemic embolism were similar with NOACs and
      warfarin, but NOACs were associated with significantly lower risks of all-cause
      mortality, major bleeding and intracranial haemorrhage but higher risk of
      gastrointestinal bleeding. Better safety suggests NOACs as preferred treatment
      for patients with atrial fibrillation starting oral anticoagulation.

PMID- 29018535
TI  - Left ventricular longitudinal systolic function analysed by 2D speckle-tracking
      echocardiography in heart failure with preserved ejection fraction: a meta
      analysis.
AB  - BACKGROUND: The purpose of this meta-analysis was to confirm if the global
      longitudinal systolic function of the left ventricle (LV) is altered in patients
      with heart failure with preserved ejection fraction (HFpEF). METHODS: We searched
      in different databases (Medline, Embase and Cochrane) studies that analysed LV
      global longitudinal systolic strain (GLS) in patients with HFpEF and in controls
      (such as healthy subjects or asymptomatic patients with arterial hypertension,
      diabetes mellitus or coronary artery disease). RESULTS: Twenty-two studies (2284
      patients with HFpEF and 2302 controls) were included in the final analysis.
      Patients with HFpEF had significantly lower GLS than healthy subjects (mean 
      15.7% (range -12% to -18.9%) vs mean -19.9% (range -17.1% to -21.5%), weighted
      mean difference -4.2% (95% CI -3.3% to -5.0%), p < 0.001, respectively). In
      addition, patients with HFpEF had also significantly lower GLS than asymptomatic
      patients (mean -15.5% (range -13.4% to -18.4%) vs mean -18.3% (range -15.1% to 
      20.4%), weighted mean difference -2.8%(95% CI -1.9% to -3.6%), p < 0.001,
      respectively). In line, 10 studies showed that the rate of abnormal GLS was
      significantly higher in patients with HFpEF (mean 65.4% (range 37%-95%)) than in
      asymptomatic subjects (mean 13% (range 0%-29.6%)). Regarding the prognostic
      relevance of abnormal GLS in HFpEF, two multicentre studies with large sample
      size (447 and 348) and high number of events (115 and 177) showed that patients
      with abnormal GLS had worse cardiovascular (CV) outcomes than those with normal
      GLS (HR for CV mortality and HF hospitalisation 2.14 (95% CI 1.26 to 3.66) and
      1.94 (95% CI 1.22 to 3.07)), even adjusting these analyses for multiples clinical
      and echocardiographic variables. CONCLUSION: The present meta-analysis analysing
      2284 patients with HFpEF and 2302 controls confirms that the longitudinal
      systolic function of the LV is significantly altered in high proportion of
      patients with HFpEF. Further large multicentre studies with the aim to confirm
      the prognostic role of abnormal GLS in HFpEF are warranted.

PMID- 29018537
TI  - Safety, pharmacokinetics and pharmacodynamics of AMG 811, an anti-interferon
      gamma monoclonal antibody, in SLE subjects without or with lupus nephritis.
AB  - OBJECTIVE: To evaluate safety, pharmacokinetics and pharmacodynamics of anti
      interferon (IFN)-gamma monoclonal antibody AMG 811 in subjects with SLE without
      or with lupus nephritis (LN). METHODS: In this phase Ib, randomised, multiple
      dose escalation study (NCT00818948), subjects without LN were randomised to
      subcutaneous AMG 811 (6, 20 or 60 mg) or placebo and subjects with LN were
      randomised to subcutaneous AMG 811 (20, 60 or 120 mg) or placebo every four weeks
      for three total doses. Outcomes included incidence of adverse events (AEs);
      pharmacokinetics; levels of serum proteins (CXCL-10, interleukin 18, monocyte
      chemotactic protein-1); changes in gene transcript profiles and clinical
      parameters (Safety of Estrogen in Lupus Erythematosus National Assessment
      Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores,
      proteinuria, anti-double-stranded DNA (anti-dsDNA) antibodies, C3 complement, C4
      complement). RESULTS: Fifty-six subjects enrolled (28 SLE without LN; 28 with
      LN). Baseline mean SELENA-SLEDAI scores were 2.2 and 12.0 for SLE subjects
      without and with LN, respectively. Most subjects reported an AE; no meaningful
      imbalances were observed between AMG 811 and placebo. Pharmacokinetic profiles
      were similar and mostly dose-proportional in subjects without or with LN. AMG 811
      treatment reduced CXCL-10 protein levels and blood-based RNA IFN-gamma Blockade
      Signature compared with placebo. Reductions were less pronounced and not
      sustained in subjects with LN, even at the highest dose tested, compared with
      subjects without LN. No effect on SELENA-SLEDAI scores, proteinuria, C3 or C4
      complement levels, or anti-dsDNA antibodies was observed. CONCLUSION: AMG 811
      demonstrated favourable pharmacokinetics and acceptable safety profile but no
      evidence of clinical impact. IFN-gamma-associated biomarkers decreased with AMG
      811; effects were less pronounced and not sustained in LN subjects. TRIAL
      REGISTRATION NUMBER: NCT00818948; results.

PMID- 29018538
TI  - Replacement of warfarin with a novel oral anticoagulant in endoscopic mucosal
      resection: a multicentre, open-label, randomised controlled trial.
AB  - INTRODUCTION: This randomised controlled trial aims to compare the efficacy of
      warfarin replacement with apixaban without postoperative resumption of heparin
      with that of conventional heparin bridging in patients taking warfarin and
      scheduled to undergo endoscopic mucosal resection (EMR): specifically, by
      checking for reduction in proportion of postoperative bleeding following EMR.
      METHODS AND ANALYSIS: The multicentre, open-label randomised parallel-group,
      controlled intervention study regards patients taking warfarin who are scheduled
      to undergo colon EMR. Enrolled patients have been taking oral warfarin for non
      valvular atrial fibrillation or venous thrombosis on an outpatient basis, and
      have been found to have a colorectal polyp (including adenoma or early-stage
      cancer) for which EMR was indicated. They are assigned to one of two groups. The
      primary endpoint is proportion of postoperative bleeding. The secondary endpoints
      are hospital stay length, therapeutic endoscopy outcomes such as proportion of en
      bloc resection, proportion of perforation, proportion of intraoperative bleeding,
      incidence of cerebral infarction/systemic embolism events, incidence of adverse
      events and serious adverse events, and proportion of postoperative therapeutic
      endoscopy. ETHICS AND DISSEMINATION: This trial was approved by the National
      Hospital Organization Central Review Board for Clinical Trials (19 April 2016).
      DISCUSSION: The paucity of reports with high evidence levels was considered
      problematic when the Japan Gastroenterological Endoscopy Society's
      gastroenterological endoscopy guidelines were revised in 2012. The results of
      this trial will have high medical significance, as its data could serve as the
      basis for revisions in the next edition of the guidelines. TRIAL REGISTRATION
      NUMBER: This trial was registered in the University Hospital Medical Information
      Network Clinical Trials Registry (UMIN-CTR) accepted from the International
      Committee of Medical Journal Editors (ICMJE). UMIN000021947; Pre-results.

PMID- 29018539
TI  - Clinical characteristics of antimitochondrial antibody-positive patients at a
      safety net health care system in Arizona.
AB  - BACKGROUND AND AIMS: To assess whether aspartate aminotransferase (AST), alanine
      aminotransferase (ALT) and alkaline phosphatase (AP) levels can predict the
      diagnosis of primary biliary cholangitis (PBC) or any other diagnoses and whether
      PBC occurs either simultaneously or independently of other liver diseases among
      antimitochondrial antibody (AMA)-positive patients. METHODS: Demographic and
      clinical variables were assessed in 90 AMA-positive patients with and without
      liver biopsies. These patients were further categorised as having a diagnosis of
      PBC, overlap syndrome or 'not established with a diagnosis of PBC'. Receiver
      operating characteristic curves were constructed to determine the thresholds of
      liver enzymes that predict these three diagnoses. RESULTS: The 48 patients with
      liver biopsies were more frequently female and had significantly higher AP levels
      compared with the non-liver biopsy group. Based on liver biopsy findings, 12, 12
      and 22 patients were assigned a diagnosis of PBC, overlap syndrome with
      autoimmune hepatitis and PBC and 'not established diagnosis of PBC',
      respectively. Seven of 12 patients classified as PBC had AP level of ?200 IU.
      AST, ALT and AP levels were significant predictors of a diagnosis of overlap
      syndrome compared with the rest of the patients; however, these tests were not
      discriminatory between diagnoses of PBC and 'not established with PBC'. Findings
      of fatty liver and bile duct injury on liver biopsies were not significantly
      associated with any liver test pattern. CONCLUSIONS: As the liver test pattern
      did not correlate with the liver biopsy findings of PBC or other non-PBC
      diagnoses in AMA-positive patients at risk for other disease, a liver biopsy
      and/or non-invasive liver assessment along with serum liver tests should be
      interpreted to complete liver evaluation.

PMID- 29018540
TI  - Efficacy of individualised diets in patients with irritable bowel syndrome: a
      randomised controlled trial.
AB  - BACKGROUND: Patients with irritable bowel syndrome (IBS) are often placed on
      diets guided by food intolerance assays, although these have not been validated.
      We assessed the effects of individualised diets in patients with IBS guided by a
      leucocyte activation test. METHODS: This is a parallel-group, double-blind,
      randomised controlled trial of 58 adults with IBS seen at an academic health
      centre in Northeast USA. Peripheral venous blood was analysed using a leucocyte
      activation test; individual foods were reported to produce positive or negative
      results. Participants were randomised to a 4-week diet with either individualised
      guidance to eliminate foods with positive assay results and allow foods with
      negative assay results (intervention), or with individualised guidance, matched
      in rigour and complexity, to eliminate foods with negative assay results and
      allow foods with positive assay results (comparison). The primary outcome was
      between-group differences in the IBS Global Improvement Scale (GIS). Secondary
      outcomes included reductions in IBS Symptom Severity Scale (SSS) scores and
      increases in IBS Adequate Relief (AR) and Quality of Life (QOL) scores. An
      aptamer-based proteomic analysis was conducted in strong responders. RESULTS: The
      intervention group had significantly greater increases in mean GIS score after 4
      weeks (0.86 vs comparison; 95% CI 0.05 to 1.67; p=0.04) and 8 weeks (1.22 vs
      comparison; 95% CI 0.22 to 2.22; p=0.02). The intervention group also had
      significantly greater reductions in mean SSS score at 4 weeks (-61.78 vs
      comparison; 95% CI -4.43 to -119.14; p=0.04) and 8 weeks (-66.42 vs comparison;
      95% CI -5.75 to -127.09; p=0.03). There were no significant differences between
      intervention and comparison groups in mean AR or QOL scores. A reduction in
      neutrophil elastase concentration was associated with reduced symptoms.
      CONCLUSIONS: Elimination diets guided by leucocyte activation tests reduced
      symptoms. These findings could lead to insights into the pathophysiology of IBS.
      TRIAL REGISTRATION NUMBER: NCT02186743.

PMID- 29018541
TI  - Results from a retrospective analysis of colonoscopies for Inflammatory bowel
      disease and colorectal cancer in a Lebanese tertiary care centre.
AB  - BACKGROUND AND AIMS: Inflammatory bowel diseases (IBDs) and colorectal cancer
      have an increased impact on the Lebanese population's morbidity and mortality.
      This study evaluated the situation of IBD and colorectal cancer at a tertiary
      hospital centre in Lebanon. METHODS: 1007 patients underwent colonoscopy over a
      period of 12 months by qualified physicians. 91 patients were excluded from the
      study. Biopsy results were divided into normal versus abnormal colonic tissue.
      The abnormal section was further subdivided into number of polyps, IBD, dysplasia
      and cancer. RESULTS: Out of 916 individuals included, 61 cases of Crohn's colitis
      (CC) (6.7%) and 24 cases of ulcerative colitis (UC) (2.7%) were identified. A
      total of 92 cases of colorectal cancer (10.04%) were also identified. There was a
      slight male predominance in both groups of IBD without any statistical
      significance. One statistical significance was reported in favour to age<50 years
      in both IBD groups with a mean age of 37.9+/-9.7 years and 34.4+/-6.4 years for
      CC and UC, respectively. The incidence of granuloma in the CC group was 8.9%
      without any correlation compared with age or gender. No correlation was made
      between colorectal cancer and the existence of any IBD type. The data showed that
      age >50 years and male gender significantly correlate with an increased incidence
      of precancerous and cancerous polyps in the colon. They significantly correlate
      with adenocarcinoma. The estimated incidence of colorectal cancer, CC and UC was
      54.1, 35.8 and 14.1 per 100 000, respectively, with a denominator of 169 959
      patients per year. CONCLUSION: Within the limitations of this study, the
      incidence of colorectal cancer and IBD falls in the high range compared with
      similar European and American studies. Our data are biased because of the
      tertiary centre setting but they can be considered as base for further
      investigations.

PMID- 29018542
TI  - Spatiotemporal characteristics of motor actions by blind long jump athletes.
AB  - BACKGROUND: Blind people depend on spatial and temporal representations to
      perform activities of daily living and compete in sport. OBJECTIVE: The aim of
      this study is to determine the spatiotemporal characteristics of long jumps
      performed by blind athletes and compare findings with those reported for sighted
      athletes. METHODS: We analysed a sample of 12 male athletes competing in the F11
      Long Jump Finals at the Paralympic Games in London 2012. Performances were
      recorded using four high-speed cameras, and speeds were measured using a radar
      speed gun. The images were processed using validated image analysis software.
      RESULTS: The long jump run-up is shorter in blind athletes than in sighted
      athletes. We observed statistically significant differences for body centre of
      mass velocity and an increase in speed over the last three strides prior to take
      off, contrasting with reports for sighted athletes and athletes with less severe
      visual impairment, who maintain or reduce their speed during the last stride.
      Stride length for the last three strides was the only spatial characteristic that
      was not significantly associated with effective jump distance. Blind long jumpers
      extend rather than shorten their last stride. Contact time with the take-off
      board is longer than that reported for sighted athletes. CONCLUSION: The actions
      of blind long jumpers, unlike those without disabilities, do not vary their leg
      actions during the final runway approach for optimal placement on the take-off
      board.

PMID- 29018543
TI  - Validity of Fitbit's active minutes as compared with a research-grade
      accelerometer and self-reported measures.
AB  - OBJECTIVES: The main purpose of the study was to assess the validity between the
      Fitbit and ActiGraph GT3X+ accelerometer. The specific aims were to determine
      the: (1) concurrent validity between the various models of the Fitbit and the
      GTX3+ accelerometer as the criterion measure for: number of steps and active
      minutes averaged over a single-day and 7-day period; (2) validity of the two
      devices with the International Physical Activity Questionnaire (IPAQ) for the
      number of daily active minutes performed. METHODS: Fifty-three subjects wore a
      Fitbit and ActiGraph concurrently for 7 days. Data were analysed using
      correlation coefficients, t-tests to assess mean comparisons and Bland-Altman
      plots to determine agreement between the Fitbit and the ActiGraph. RESULTS: The
      correlations between the Fitbit and ActiGraph for steps per day and per 7 days
      were r=0.862 and 0.820, respectively with significant mean differences between
      both devices. Bland-Altman analyses revealed agreement between the Fitbit and the
      ActiGraph for 7-day active minutes only. The correlations between the Fitbit and
      ActiGraph for active minutes per day and per 7 days were r=0.695 and r=0.658,
      respectively, with no significant mean differences between both devices. No
      significant correlations were found between the IPAQ and the other two devices.
      CONCLUSIONS: The data produced by the Fitbit were consistent with the ActiGraph
      when the means of each device were compared over the 1-day and 7-day time
      periods. However, Bland-Altman analyses revealed that the Fitbit agreed with the
      ActiGraph when used to measure physical activity levels over a 7-day span only.

PMID- 29018544
TI  - Verbal augmented feedback in the rehabilitation of lower extremity
      musculoskeletal dysfunctions: a systematic review.
AB  - BACKGROUND: Verbal augmented feedback (VAF) is commonly used in physiotherapy
      rehabilitation of individuals with lower extremity musculoskeletal dysfunction or
      to induce motor learning for injury prevention. Its effectiveness for
      acquisition, retention and transfer of learning of new skills in this population
      is unknown. OBJECTIVES: First, to investigate the effect of VAF for
      rehabilitation and prevention of lower extremity musculoskeletal dysfunction.
      Second, to determine its effect on motor learning and the stages of acquisition,
      retention and transfer in this population. DESIGN: Systematic review designed in
      accordance with the Centre for Reviews and Dissemination and reported in line
      with Preferred Reporting Items for Systematic Review and Meta-analysis. METHOD:
      MEDLINE, Embase, PubMed and five additional databases were searched to identify
      primary studies with a focus on VAF for prevention and rehabilitation of lower
      extremity musculoskeletal dysfunction. One reviewer screened the titles and
      abstracts. Two reviewers retrieved full text articles for final inclusion. The
      first reviewer extracted data, whereas the second reviewer audited. Two reviewers
      independently assessed risk of bias and quality of evidence using Cochrane
      Collaboration's tool and Grading of Recommendations Assessment, Development and
      Evaluation, respectively. RESULTS: Six studies were included, with a total sample
      of 304 participants. Participants included patients with lateral ankle sprain
      (n=76), postoperative ACL reconstruction (n=16) and healthy individuals in injury
      prevention (n=212). All six studies included acquisition, whereas retention was
      found in five studies. Only one study examined transfer of the achieved motor
      learning (n=36). VAF was found to be effective for improving lower extremity
      biomechanics and postural control with moderate evidence from five studies.
      CONCLUSION: VAF should be considered in the rehabilitation of lower extremity
      musculoskeletal dysfunctions. However, it cannot be unequivocally confirmed that
      VAF is effective in this population, owing to study heterogeneity and a lack of
      high-quality evidence. Nevertheless, positive effects on lower extremity
      biomechanics and postural control have been identified. This suggests that
      further research into this topic is warranted where an investigation of long-term
      effects of interventions is required. All stages (acquisition, retention and
      transfer) should be evaluated.

PMID- 29018545
TI  - Concussion in field hockey: a retrospective analysis into the incidence rates,
      mechanisms, symptoms and recovery of concussive injuries sustained by elite field
      hockey players.
AB  - OBJECTIVES: To identify the incidence and mechanisms of concussion in elite Field
      Hockey in different age groups and also the postconcussion symptoms and recovery
      times. METHODS: Data was collected retrospectively, for both training and
      matches, over a 12-month period from national level Field Hockey players across
      under-16, under-18, under-21, Development and Senior players. Mechanism of injury
      (including player role and field position), postconcussive symptoms and recovery
      times were recorded following a semistructured interview with each player.
      Additional information on training hours, matches and squad size were also
      recorded in order to calculate the incidence per 1000 match hours. RESULTS: Of
      the 28 recorded cases, only 11 could be included in the study. Women had the
      highest incidence of concussion, with the majority being in the under-21 age
      group. Overall incidence varied from 3/1000 match hours in training to 0.02/1000
      match hours in matches, with an overall incidence of 0-0.02/1000 match hours
      across all age groups. The most common mechanism of injury was collision with
      another player, followed by impact from a stick or ball Midfield and attacking
      forwards sustained the highest incidence of concussion. None of the concussed
      athletes wore protective headgear (there were no cases of concussion in goal
      keepers) and all occurred in open play rather than a penalty corner (when
      protective headgear is often worn). Postconcussion headaches and difficulty
      concentrating were the most commonly reported postconcussion symptoms. Average
      recovery time and return-to-play was 2-4 weeks. CONCLUSIONS: Due to the low
      numbers, only limited conclusions can be made, but it would appear that the risk
      of concussion in elite Field Hockey is low. As age and skill increases, the risk
      decreases. Postconcussion symptoms and average return-to-play times are similar
      to other sports. From this study, no conclusions can be made as to the role of
      protective headgear to reduce the risk of concussion.

PMID- 29018546
TI  - Patient safety and quality of care in mental health: a world of its own?
AB  - Quality and safety in healthcare, as an academic discipline, has made significant
      progress over recent decades, and there is now an active and established
      community of researchers and practitioners. However, work has predominantly
      focused on physical health, despite broader controversy regarding the attention
      paid to, and significance attributed to, mental health. Work from both
      communities is required in order to ensure that quality and safety is actively
      embedded within mental health research and practice and that the academic
      discipline of quality and safety accurately represents the scientific knowledge
      that has been accumulated within the mental health community.

PMID- 29018547
TI  - A Devil's dictionary for mental health.
AB  - Clinical psychiatry, for all its emphasis on scientific rigour, is mediated
      mainly by words rather than by numbers. As with other professional areas, it has
      developed its own set of jargon words and phrases. Many of these are not the
      technical terms traditionally seen as jargon, but standard English words and
      phrases used in an idiosyncratic way. They therefore go unnoticed as jargon,
      while enfeebling our communications. I have used the template of Ambrose Bierce's
      The Devil's Dictionary to highlight some examples, with the aim of helping us all
      to talk, write and, perhaps, think more clearly.

PMID- 29018548
TI  - Personality disorder services in England: findings from a national survey.
AB  - Aims and method We aimed to evaluate the availability and nature of services for
      people affected by personality disorder in England by conducting a survey of
      English National Health Service (NHS) mental health trusts and independent
      organisations. Results In England, 84% of organisations reported having at least
      one dedicated personality disorder service. This represents a fivefold increase
      compared with a 2002 survey. However, only 55% of organisations reported that
      patients had equal access across localities to these dedicated services.
      Dedicated services commonly had good levels of service use and carer involvement,
      and engagement in education, research and training. However, a wider
      multidisciplinary team and a greater number of biopsychosocial interventions were
      available through generic services. Clinical implications There has been a
      substantial increase in service provision for people affected by personality
      disorder, but continued variability in the availability of services is apparent
      and it remains unclear whether quality of care has improved.

PMID- 29018549
TI  - Perceptions and knowledge of antipsychotics among mental health professionals and
      patients.
AB  - Aims and method To assess the patients' most influential concerns regarding long
      acting injectable antipsychotics (LAIs) and mental health professionals'
      preconceptions about these concerns. For both groups, to assess the level of
      knowledge about LAIs. This cross-sectional study used semi-structured interviews
      of patients with schizophrenia or schizoaffective disorder (n = 164), nurses (n =
      43) and physicians (n = 20). Results The mental health professionals
      overestimated many of the patients' fears of LAIs, and the expressed fears
      exceeded the actual experiences of patients already on LAIs. Acceptance to switch
      to LAIs was associated with shorter time from diagnosis. Nurses and patients
      disclosed limited knowledge of antipsychotics. Clinical implications Physicians
      and nurses should aim to identify the individual patient's concerns about LAIs in
      the discussion about choice of antipsychotic treatment early in the course of
      illness.

PMID- 29018550
TI  - Mental capacity legislation in the UK: systematic review of the experiences of
      adults lacking capacity and their carers.
AB  - Aims and method Capacity legislation in the UK allows substitute decision-making
      for adults lacking capacity. Research has explored the experiences of such adults
      and their carers in relation to the Adults with Incapacity (Scotland) Act 2000,
      and the Mental Capacity Act 2005 in England and Wales. A systematic review of the
      relevant research was performed using a framework method. Results The legislation
      provided mechanisms for substitute decision-making which were seen as useful, but
      there were negative experiences. Decision-making did not always seem to follow
      the legislative principles. Awareness of the legislation was limited. Most
      research was qualitative and some was of low methodological quality. Data were
      too heterogeneous to allow comparisons between English and Scottish law. Clinical
      implications Capacity legislation was generally viewed positively. However, some
      experiences were perceived negatively, and the potential benefits of the
      legislation were not always utilised.

PMID- 29018551
TI  - Does the cognitive therapy of depression rest on a mistake?
AB  - Cognitive therapy for depression is common practice in today's National Health
      Service, yet it does not work well. Aaron Beck developed it after becoming
      disillusioned with the psychoanalytic theory and therapy he espoused and
      practised. But Beck's understanding of psychoanalysis appears to have been
      seriously flawed. Understood rightly, the psychoanalytic approach offers a cogent
      theory and therapy for depression which, unlike the cognitive approach, takes us
      to its emotional-motivational roots. A clinically successful therapy can afford
      to eschew theory and rest on its pragmatic laurels. This is not the case for
      cognitive therapy. The time is right to re-examine the psychoanalytic theory and
      treatment of depression.

PMID- 29018552
TI  - The cognitive therapy of depression rests on substantial theoretical, empirical
      and clinical foundations: a reply to Dr Gipps.
AB  - Dr Gipps claims that the cognitive therapy for depression rests on a mistake. But
      his anachronistic analysis of Beck's early research from the perspective of
      current psychoanalytic theory misses the point. The value of the research was not
      that it disproved psychoanalytic theory, but that it generated a model of
      depression that has revolutionised psychotherapy research. Psychoanalysts are
      belatedly adopting research methods that Beck pioneered half a century ago. The
      cognitive model of depression has explanatory power for both maintenance and
      vulnerability and has substantial research underpinning it. Cognitive therapy for
      depression has a larger body of evidence for its efficacy and relapse prevention
      effect than any other psychotherapy. Transference-focused approaches to
      depression have yet to establish themselves in the same way.

PMID- 29018553
TI  - Suicide patterns on the London Underground railway system, 2000-2010.
AB  - Aims and Method Suicidal acts on underground railway networks are an area of
      public health concern. Our aim was to review recent epidemiological patterns of
      suicidal acts on the London Underground to inform future preventive
      interventions. Data from 2000 to 2010 were obtained from the British Transport
      Police via a Freedom of Information request. Results The mean annual rate of
      suicidal acts from 2000 to 2010 was 5.8 per 100 million passenger journey stages.
      Of those who died by suicide, 77.3% were of White Northern European ethnicity. A
      fifth had a history of mental illness. Clinical implications The widening gap
      between the number of recorded suicide attempts and completed suicides is
      encouraging. Further research is required regarding the role of drug and alcohol
      use, psychiatric history and area of residence. Installation of platform screen
      doors should be considered in future railway network expansion.

PMID- 29018554
TI  - Psychiatric neurosurgery in the 21st century: overview and the growth of deep
      brain stimulation.
AB  - Ambulatory deep brain stimulation (DBS) became possible in the late 1980s and was
      initially used to treat people with movement disorders. Trials of DBS in people
      with treatment-resistant psychiatric disorder began in the late 1990s, initially
      focusing on obsessive-compulsive disorder, major depressive disorder and Tourette
      syndrome. Despite methodological issues, including small participant numbers and
      lack of consensus over brain targets, DBS is now being trialled in a wide range
      of psychiatric conditions. There has also been more modest increase in ablative
      procedures. This paper reviews these developments in the light of contemporary
      brain science, considers future directions and discusses why the approach has not
      been adopted more widely within psychiatry.

PMID- 29018555
TI  - Teaching provision for old age psychiatry in medical schools in the UK and
      Ireland: a survey.
AB  - Aims and method This work builds on a survey first done in 1999 to understand how
      old age psychiatry teaching is embedded in undergraduate medical schools in the
      UK and Ireland and the influence of academic old age psychiatrists on teaching
      processes. We invited deans of 31 medical schools in the UK and Ireland in 2015
      to complete an online survey to reassess the situation 16 years later. Results
      Response rate was 74%. As found in the original survey, there was variation
      across medical schools in how old age psychiatry is taught. Half of schools
      stated there was not enough space in the curriculum dedicated to old age
      psychiatry, and not all medical school curricula offered a clinical attachment.
      Medical schools that involved academic old age psychiatrists in teaching (59%)
      showed a greater diversity of teaching methods. Clinical implications There is a
      need to recognise the importance of old age psychiatry teaching, with the
      consensus of opinion continuing to be that more curriculum space needs to be
      given to old age psychiatry. To achieve this we advocate increasing the number of
      old age psychiatrists with teaching roles, as relying on academics to teach and
      lead on curriculum development is challenging given their greater research
      pressures.

PMID- 29018557
TI  - Investigating a serious incident - a personal perspective.

PMID- 29018556
TI  - Profile: Derek Summerfield - politics and psychiatry.

PMID- 29018558
TI  - Management of common mental disorders for psychogeriatric patients in Hong Kong -
      a comparison of two clinics.

PMID- 29018559
TI  - Author's reply - the cognitive therapy of depression.

PMID- 29018560
TI  - Corrections.
AB  - [This corrects the article on p. 234 in vol. 41, PMID: 28811920.][This corrects
      the article on p. 197 in vol. 41, PMID: 28811913.][This corrects the article on
      p. 187 in vol. 41, PMID: 28811911.].

PMID- 29018561
TI  - Disturbed EEG sleep, paranoid cognition and somatic symptoms identify veterans
      with post-traumatic stress disorder.
AB  - BACKGROUND: Chronic post-traumatic stress disorder (PTSD) behavioural symptoms
      and medically unexplainable somatic symptoms are reported to occur following the
      stressful experience of military combatants in war zones. AIMS: To determine the
      contribution of disordered EEG sleep physiology in those military combatants who
      have unexplainable physical symptoms and PTSD behavioural difficulties following
      war-zone exposure. METHOD: This case-controlled study compared 59 veterans with
      chronic sleep disturbance with 39 veterans with DSM-IV and clinician-administered
      PTSD Scale diagnosed PTSD who were unresponsive to pharmacological and
      psychological treatments. All had standardised EEG polysomnography, computerised
      sleep EEG cyclical alternating pattern (CAP) as a measure of sleep stability,
      self-ratings of combat exposure, paranoid cognition and hostility subscales of
      Symptom Checklist-90, Beck Depression Inventory and the Wahler Physical Symptom
      Inventory. Statistical group comparisons employed linear models, logistic
      regression and chi-square automatic interaction detection (CHAID)-like decision
      trees. RESULTS: Veterans with PTSD were more likely than those without PTSD to
      show disturbances in non-rapid eye movement (REM) and REM sleep including delayed
      sleep onset, less efficient EEG sleep, less stage 4 (deep) non-REM sleep, reduced
      REM and delayed onset to REM. There were no group differences in the prevalence
      of obstructive sleep apnoeas/hypopnoeas and periodic leg movements, but sleep
      disturbed, non-PTSD military had more EEG CAP sleep instability. Rank order
      determinants for the diagnosis of PTSD comprise paranoid thinking, onset to REM
      sleep, combat history and somatic symptoms. Decision-tree analysis showed that a
      specific military event (combat), delayed onset to REM sleep, paranoid thinking
      and medically unexplainable somatic pain and fatigue characterise chronic PTSD.
      More PTSD veterans reported domestic and social misbehaviour. CONCLUSIONS:
      Military combat, disturbed REM/non-REM EEG sleep, paranoid ideation and medically
      unexplained chronic musculoskeletal pain and fatigue are key factors in
      determining PTSD disability following war-zone exposure. DECLARATION OF INTEREST:
      None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016. This is
      an open access article distributed under the terms of the Creative Commons Non
      Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 29018562
TI  - Local availability of green and blue space and prevalence of common mental
      disorders in the Netherlands.
AB  - BACKGROUND: Previous studies revealed a relationship between residential green
      space availability and health, especially mental health. Studies on blue space
      are scarcer and results less conclusive. AIMS: To investigate the hypotheses that
      green and blue space availability are negatively associated with anxiety and mood
      disorders, and positively associated with self-reported mental and general
      health. METHOD: Health data were derived from a nationally representative survey
      (NEMESIS-2, n=6621), using a diagnostic interview to assess disorders. Green and
      blue space availability were expressed as percentages of the area within 1 km
      from one's home. RESULTS: The hypotheses were confirmed, except for green space
      and mood disorders. Associations were generally stronger for blue space than for
      green space, with ORs up to 0.74 for a 10%-point increase. CONCLUSIONS: Despite
      the different survey design and health measures, the results largely replicate
      those of previous studies on green space. Blue space availability deserves more
      systematic attention. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The
      Royal College of Psychiatrists 2016. This is an open access article distributed
      under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC
      ND) license.

PMID- 29018563
TI  - Pharmacotherapy of post-traumatic stress disorder: going beyond the guidelines.
AB  - SUMMARY: This article discusses the study of Harpaz-Rotem and associates, who
      examined patterns of medication use in first-diagnosed veterans with post
      traumatic stress disorder (PTSD). It considers the difference between practice
      guidelines and actual prescribing; selectively identifies issues with
      antidepressants, antipsychotics, benzodiazepines and prazosin; and reviews the
      possible impact of new medications in the pipeline. DECLARATION OF INTERESTS: In
      the past 36 months, J.D. has received compensation for consulting with Edgemont,
      Turing and Tonix Pharmaceuticals; royalties in connection with publications by
      Springer, Guilford and McFarland Publishers and use of the Connor-Davidson
      Resilience Scale, Davidson Trauma Scale, Social Phobia Inventory (SPIN) and Mini
      SPIN; service on the INTRuST Data Safety and Monitoring Board, University of
      California, San Diego. COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2016. This is an open access article distributed under the terms of
      the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 29018565
TI  - Health-related quality of life and depression among participants in the Sjogren's
      International Collaborative Clinical Alliance registry.
AB  - OBJECTIVE: To examine health-related quality of life (HRQoL) and depression among
      participants in an international Sjogren's syndrome (SS) registry, comparing
      those with and without SS. METHODS: Cross-sectional study of participants in the
      Sjogren's International Collaborative Clinical Alliance (SICCA) registry. The
      2016 American College of Rheumatology/European League Against Rheumatism SS
      classification criteria were used to determine disease status. HRQoL was assessed
      using the Short Form 12, version 2 Health Survey to derive scores for physical
      component summary (PCS) and mental component summary (MCS). Depression was
      assessed using the 9-Item Patient Health Questionnaire. Multivariate linear and
      logistic regression analyses were performed to identify predictors of HRQoL and
      depression while controlling for potential confounders. RESULTS: Among 2401 SICCA
      participants who had symptoms of dry eyes and dry mouth, 1051 had SS (44%) and
      1350 did not (56%). After controlling for confounders, when compared with non-SS
      participants, those with SS had better PCS (p<0.001, beta=2.43, 95% CI 1.57 to
      3.29), MCS (p=0.002, beta=1.37, 95% CI 0.50 to 2.23) and lower adjusted odds of
      depression (p<0.001, OR 0.67, 95% CI 0.55 to 0.81). Other significant predictors
      of HRQoL and depression included employment, country of residence and use of
      medication with anticholinergic effect or for management of SS-related signs and
      symptoms. CONCLUSION: Our results suggest that among symptomatic patients, having
      a diagnosis of SS may be associated with better emotional and psychological well
      being compared with patients without a diagnosis. Having a definitive diagnosis
      of SS may encourage patients to obtain a better understanding of their disease
      and have coping mechanisms in place to better manage their symptoms.

PMID- 29018564
TI  - Achieving comprehensive disease control in patients with early and established
      rheumatoid arthritis treated with adalimumab plus methotrexate versus
      methotrexate alone.
AB  - OBJECTIVE: To evaluate the achievement of comprehensive disease control (CDC)
      following 1 year of treatment with adalimumab+methotrexate versus methotrexate
      alone and whether early achievement of remission (at week 24 or 26) is associated
      with CDC at week 52 in patients with either early or established rheumatoid
      arthritis (RA). METHODS: Post hoc analyses were conducted in three clinical
      studies assessing treatment with adalimumab+methotrexate: DE019 (NCT00195702)
      enrolled patients with established RA who were methotrexate inadequate
      responders; OPTIMA (NCT00420927) and PREMIER (NCT00195663) enrolled methotrexate
      naive patients with early RA. In OPTIMA, patients not achieving stable low
      disease activity at weeks 22 and 26 in the placebo+methotrexate group could
      receive open-label adalimumab+methotrexate for 52 weeks (Rescue ADA arm). CDC was
      defined as the simultaneous achievement of clinical remission (DAS28(CRP)<2.6),
      normal function (HAQ-DI<0.5) and absence of radiographic progression
      (DeltamTSS<=0.5). RESULTS: Regardless of disease duration, significantly more
      patients receiving adalimumab+methotrexate achieved CDC compared with
      methotrexate alone. In the adalimumab+methotrexate group, a numerically greater
      proportion of patients with early RA (~25%) versus established RA (14%) achieved
      CDC at 1 year; achievement of CDC was notably greater among patients who met
      criteria for remission at week 24 or 26 (~50% of patients with early RA and 39%
      with established RA). CONCLUSION: Treatment with adalimumab+methotrexate
      increases the likelihood of achieving CDC in patients with either early or
      established RA. Clinical remission at week 24 or 26 is associated with
      achievement of CDC at week 52. TRIAL REGISTRATION NUMBER: DE019 (NCT00195702),
      OPTIMA (NCT00420927), PREMIER (NCT00195663); Post-results.

PMID- 29018566
TI  - Risks of smoking and benefits of smoking cessation on hospitalisations for
      cardiovascular events and respiratory infection in patients with rheumatoid
      arthritis: a retrospective cohort study using the Clinical Practice Research
      Datalink.
AB  - OBJECTIVES: To investigate the associations between smoking status, smoking
      cessation and hospitalisations for cardiovascular events (CVE) and respiratory
      tract infections (RTI) in an inception cohort of patients with rheumatoid
      arthritis (RA). METHODS: The study was set within UK primary care electronic
      health records (the Clinical Practice Research Datalink) linked to hospital
      inpatient data (Hospital Episode Statistics). Patients with RA were followed from
      diagnosis to hospitalisation with a record of CVE or RTI, leaving their general
      practice, death, or 10 January 2012, whichever was earliest. Smoking status
      (never, current, former) was defined using primary care data and could vary over
      time. Survival analysis was performed using Cox regression (first event) and
      conditional risk set models (multiple RTIs). RESULTS: 5677 patients were included
      in the cohort: 68% female, median age 61 years. The age-adjusted and sex-adjusted
      risks of hospitalisation for CVE or RTI were more than twice as high in current
      vs never smokers (CVE HR (95% CI) 2.19 (1.44 to 3.31); RTI 2.18 (1.71 to 2.78)).
      The risks for both outcomes were significantly higher in current compared with
      former smokers (CVE 1.51 (1.04 to 2.19), RTI 1.29 (1.04 to 1.61)). For each
      additional year of smoking cessation, the risk of first CVE and RTI
      hospitalisation fell significantly, approximately 25% and 15% respectively in the
      adjusted models. CONCLUSIONS: Patients with RA who smoke have an increased risk
      of hospitalisation with CVE or RTI compared with never and former smokers. The
      risk decreases for each additional year of smoking cessation. Patients with RA
      who smoke should be advised to stop smoking.

PMID- 29018567
TI  - Do we need bone mineral density to estimate osteoporotic fracture risk? A 10-year
      prospective multicentre validation study.
AB  - OBJECTIVE: Evaluate the performance of FRAX(r), with and without bone mineral
      densitometry (BMD), in predicting the occurrence of fragility fractures over 10
      years. METHODS: Participants aged >=40 years at baseline, with a complete set of
      data and a minimum of 8.5 years of follow-up were identified from three cohorts
      (n=2626). Ten-year fracture risk at baseline were estimated with FRAX(r) and
      assessed by comparison with observed fractures and receiver operating
      characteristic analysis. RESULTS: During a mean (SD) follow-up of 9.12 (1.5)
      years, 178 participants suffered a major osteoporotic (MOP) fracture and 28
      sustained a hip fracture. The predictive performance of FRAX(r) was superior to
      that of BMD alone for both MOP and hip fractures. The area under the curve (AUC)
      of FRAX(r) without BMD was 0.76 (95% CI 0.72 to 0.79) for MOP fractures and 0.78
      (95% CI 0.69 to 0.86) for hip fractures. No significant improvements were found
      when BMD was added to clinical variables to predict either MOP (0.78, 95% CI 0.74
      to 0.82, p=0.25) or hip fractures (0.79, 95% CI 0.69 to 0.89, p=0.72). AUCs for
      FRAX(r) (with and without BMD) were greater for men than for women. FRAX(r), with
      and without BMD, tended to underestimate the number of MOP fractures and to
      overestimate the number of hip fractures in females. In men, the number of
      observed fractures were within the 95% CI of the number predicted, both with and
      without BMD. CONCLUSION: FRAX(r) without BMD provided good fracture prediction.
      Adding BMD to FRAX(r) did not improve the performance of the tool in the general
      population.

PMID- 29018568
TI  - Person-focused care for young people with rheumatic and musculoskeletal diseases:
      young rheumatologists' and EULAR Young PARE perspectives.
AB  - In recent years, the evolution of healthcare challenged the management of people
      with rheumatic and musculoskeletal diseases (RMDs). From disease-centred care to
      person-focused care, a holistic approach along with patient empowerment about
      their disease, improved the physician-patient relationship and allowed to achieve
      better outcomes with lower healthcare costs. Nevertheless, RMDs may occur from
      childhood to the old age and to date very few studies have addressed the needs
      and priorities of young people with RMDs. However, the image of RMDs is still
      associated with the elderly population. In this regard, the group of young people
      with arthritis and rheumatism in Europe (PARE) was recently developed within
      European League Against Rheumatism to represent the voice of the young affected
      and to carry out projects aiming for a better understanding of these specific
      aspects. This viewpoint discusses the needs and priorities of young people
      compared with adult people with RMDs, based on the available literature and on
      the results of the PARE Youth research project, aiming to identify the next steps
      of actions that need to be taken to improve the current situation.

PMID- 29018570
TI  - Erratum: Cervical spine epidural abscess: a single center analytical comparison
      to the literature.
AB  - [This corrects the article DOI: 10.1038/scsandc.2017.36.].

PMID- 29018569
TI  - Deconstructing a multiple antibiotic resistance regulation through the
      quantification of its input function.
AB  - Many essential bacterial responses present complex transcriptional regulation of
      gene expression. To what extent can the study of these responses substantiate the
      logic of their regulation? Here, we show how the input function of the genes
      constituting the response, i.e., the information of how their transcription rates
      change as function of the signals acting on the regulators, can serve as a
      quantitative tool to deconstruct the corresponding regulatory logic. To
      demonstrate this approach, we consider the multiple antibiotic resistance (mar)
      response in Escherichia coli. By characterizing the input function of its
      representative genes in wild-type and mutant bacteria, we recognize a dual
      autoregulation motif as main determinant of the response, which is further
      adjusted by the interplay with other regulators. We show that basic attributes,
      like its reaction to a wide range of stress or its moderate expression change,
      are associated with a strong negative autoregulation, while others, like the
      buffering of metabolic signals or the lack of memory to previous stress, are
      related to a weak positive autoregulation. With a mathematical model of the input
      functions, we identify some constraints fixing the molecular attributes of the
      regulators, and also notice the relevance of the bicystronic architecture
      harboring the dual autoregulation that is unique in E. coli. The input function
      emerges then as a tool to disentangle the rationale behind most of the attributes
      defining the mar phenotype. Overall, the present study supports the value of
      characterizing input functions to deconstruct the complexity of regulatory
      architectures in prokaryotic and eukaryotic systems.

PMID- 29018571
TI  - TRAIL DR5-CTSB crosstalk participates in breast cancer autophagy initiated by
      SAHA.
AB  - To investigate the ability of SAHA-induced TRAIL DR5-CTSB crosstalk to initiate
      the breast cancer autophagy, RTCA assay was performed to assess the effect of
      SAHA on breast cancer cells, and western blot and ELISA were used to verify the
      inductive effects on expression of CTSB. Breast cancer cells were transfected
      with TRAIL DR5 siRNA to block the function of TRAIL DR5. Cell viability and
      apoptosis of breast cancer cells were analyzed using a muse cell analyzer. The
      distribution of LC3-II in TRAIL DR5-silenced breast cancer cells treated with
      SAHA was observed by immunofluorescence microscopy, the mRNA levels of autophagy
      related genes were detected by RNA microarray, and the activity of autophagy
      related signaling pathways was screened by MAPK antibody array. Results indicated
      that SAHA did indeed repress the growth of breast cancer cell lines with inducing
      CTSB expression. Western blot and ELISA results indicated that TRAIL DR5 was
      involved in the expression of CTSB in SAHA-induced breast cancer cells. Cell
      viability and apoptosis assays showed that the inactivation of TRAIL DR5 can
      significantly inhibit the effects of SAHA. An immunofluorescence assay indicated
      that, with SAHA treatment, MDA-MB-231 and MCF-7 cells underwent apparent
      morphological changes. While SAHA was added in the TRAIL-DR5 blocked cells, the
      distribution of LC3-II signal was dispersed, the intensity of fluorescence signal
      was weaker than that of SAHA alone. RNA array indicated that SAHA significantly
      increased mRNA expression of autophagy marker LC3A/B whereas the change was
      significantly reversed in TRAIL DR5-silenced cells. The results of MAPK antibody
      array showed that SAHA and TRAIL DR5 could affect the activity of AKT1, AKT2, and
      TOR protein in breast cancer cells. These results provide more evidence that SAHA
      may stimulate TRAIL DR5-CTSB crosstalk, influence the activity of downstream TOR
      signalling pathway mainly through the AKTs pathway, and initiate the autophagy of
      breast cancer cells.

PMID- 29018572
TI  - Enhanced HOXA10 sumoylation inhibits embryo implantation in women with recurrent
      implantation failure.
AB  - HOXA10 has emerged as an important molecular marker of endometrial receptivity.
      Recurrent implantation failure (RIF) after in vitro fertilization-embryo
      transplantation (IVF-ET) treatment is associated with impaired endometrial
      receptivity, but the exact underlying mechanism of this phenomenon remains
      elusive. Here we found that HOXA10 was modified by small ubiquitin like-modifier
      1 (SUMO1) at the evolutionarily conserved lysine 164 residue. Sumoylation
      inhibited HOXA10 protein stability and transcriptional activity without affecting
      its subcellular localization. SUMO1-modified HOXA10 expression was decreased in
      estradiol- and progesterone-treated Ishikawa cells. Sumoylation inhibited the
      accelerant role of HOXA10 in BeWo spheroid and mouse embryo attachment to
      Ishikawa cells. Importantly, aberrantly high SUMO1-HOXA10 expression was detected
      in mid-secretory endometria of women with RIF compared with that of the control
      fertile women. Together, our results suggest that HOXA10 sumoylation impairs the
      process of embryo implantation in vitro and takes part in the development of RIF.

PMID- 29018574
TI  - Continuing EGFR-TKI beyond radiological progression in patients with advanced or
      recurrent, EGFR mutation-positive non-small-cell lung cancer: an observational
      study.
AB  - BACKGROUND: Some patients with advanced or recurrent, epidermal growth factor
      receptor (EGFR) mutation-positive (EGFR M+) non-small-cell lung cancer (NSCLC)
      continue to receive EGFR tyrosine kinase inhibitors (TKIs) beyond radiological
      progression. METHODS: We analysed a cohort of 577 patients with EGFR M+ NSCLC,
      who had received a first-line EGFR-TKI. We classified patients according to
      clinical course and treatment patterns at Response Evaluation Criteria in Solid
      Tumors (RECIST) progressive disease (PD). We evaluated the period from RECIST PD
      to TKI discontinuation or clinical PD and also evaluated survival after RECIST PD
      and compared it between groups. RESULTS: RECIST PD was documented in 451 cases,
      of which 283 (62.7%) were clinically stable. 186 (65.7%) discontinued and 97
      (34.3%) continued the EGFR-TKI. In those who continued EGFR-TKI, median time
      between RECIST PD and clinical PD or TKI discontinuation was 5.1 months. Median
      survival after RECIST PD in patients who discontinued and continued EGFR-TKI
      after clinically stable RECIST PD was 14.6 and 15.3 months (p=0.5489),
      respectively. In multivariate analysis, continuing EGFR-TKI therapy, female
      gender, better performance status and exon 19 deletion subtype were likely
      positive predictive factors for survival after clinically stable RECIST PD.
      CONCLUSION: Our study suggests that some patients could benefit from receiving an
      EGFR-TKI beyond radiological progression.

PMID- 29018573
TI  - How many diseases is triple negative breast cancer: the protagonism of the immune
      microenvironment.
AB  - Triple negative breast cancer (TNBC) is a type of breast cancer (BC) that does
      not express the oestrogen and the progesterone receptors and the human epidermal
      growth factor receptor type 2 (HER2). Since there are no positive markers to
      reliably classify TNBC, these tumours are not yet treated with targeted
      therapies. Perhaps for this reason they are the most aggressive form of breast
      carcinomas. However, the clinical observation that these patients do not carry a
      uniformly dismal prognosis, coupled with data coming from pathology and
      epidemiology, suggests that this negative definition is not capturing a single
      clinical entity, but several. We critically evaluate this evidence in this paper,
      reviewing clinical and epidemiological data and new studies that aim to
      subclassify TNBC. Moreover, evidence on the role of tumour infiltrating
      lymphocytes (TILs) on TNBC progression, response to chemotherapy and patient
      outcome have been published. The heterogeneity, observed even at TILs level,
      highlights the idea that TNBC is much more than a single disease with a unique
      treatment. The exploration of the immune environment present at the tumour site
      could indeed help in answering the question 'How many diseases is TNBC' and will
      help to define prognosis and eventually develop new therapies, by stimulating the
      immune effector cells or by inhibiting immunological repressor molecules. In this
      review, we focus on the prospect of the patient's diverse immune signatures
      within the tumour as potential biomarkers and how they could be modulated to
      fight the disease.

PMID- 29018575
TI  - Clinical outcome of patients with chemorefractory metastatic colorectal cancer
      treated with trifluridine/tipiracil (TAS-102): a single Italian institution
      compassionate use programme.
AB  - BACKGROUND: TAS-102 improves overall survival (OS) in patients with metastatic
      colorectal cancer (mCRC) refractory to standard treatments. However, predictive
      biomarkers of efficacy are currently lacking. PATIENTS AND METHODS: We treated a
      cohort of 43 chemorefractory mCRC patients treated with TAS-102, in a single
      institution expanded access, compassionate use programme. We stratified patients
      in two groups according to number of cycles received (<6 cycles and >=6 cycles).
      OS, progression-free survival (PFS) and safety were evaluated. RESULTS: Thirteen
      out of 43 patients (30%) obtained a clinically relevant disease control with TAS
      102 therapy. Eleven of them were treated for >=6 cycles with TAS-102, reaching a
      median PFS of 7.5 months (95% CI 5.8 to 9.2 months) and a median OS of 11.2
      months (95% CI range not reached yet). A trend towards significance (p=0.08)
      between a good performance status and response to TAS-102 was observed. Further,
      7 out of the 11 TAS-102 long-treated patients achieved a clinical benefit from a
      previous treatment with regorafenib. A significant correlation between
      regorafenib and TAS-102 clinical efficacy was observed (p=0.008). Six out 13
      regorafenib-naive patients were treated with regorafenib after progression from
      TAS-102. All these patients achieved SD with a median duration of treatment with
      regorafenib of 6.1 months (range, 1.6-6.7). CONCLUSION: Patients with mCRC in
      good clinical conditions, even though having been heavily pretreated with all the
      available treatment options, could obtain a significant clinical benefit from
      treatment with TAS-102. Moreover, a previous clinical benefit obtained with
      regorafenib is potentially predictive of clinical efficacy of subsequent TAS-102
      treatment.

PMID- 29018577
TI  - Palliative treatment with radiation-emitting metallic stents in unresectable
      Bismuth type III or IV hilar cholangiocarcinoma.
AB  - BACKGROUND: The emerging data for stenting in combination with brachytherapy in
      unresectable hilar cholangiocarcinoma are encouraging. The aim of this study was
      to evaluate the efficacy and safety of radiation-emitting metallic stents (REMS)
      for unresectable Bismuth type III or IV hilar cholangiocarcinoma. PATIENTS AND
      METHODS: Consecutive patients who underwent percutaneous placement with REMS or
      uncovered self-expandable metallic stent (SEMS) for unresectable Bismuth type III
      or IV hilar cholangiocarcinoma between September 2011 and April 2016 were
      identified into this retrospective study. Data on patient demographics and
      overall survival, functional success, stent patency and complications were
      collected at the authors' hospital. RESULTS: A total of 59 patients were
      included: 33 (55.9%) in the REMS group and 26 (44.1%) in the SEMS group. The
      median overall survival was 338 days in the REMS group and 141 days in the SEMS
      group (p<0.001). The median stent patency time was 385 days for REMS and 142 days
      for SEMS (p<0.001). The functional success rate (87.9% vs 84.6%, p=0.722) and
      incidence of overall complications (27.3% vs 26.9%, p=0.999) did not differ in
      the two groups. CONCLUSIONS: Placement with REMS is safe and effective in
      palliation for unresectable Bismuth type III or IV hilar cholangiocarcinoma, and
      seems to prolong survival as well as patency of stent in these patients.

PMID- 29018576
TI  - Key differences between 13 KRAS mutation detection technologies and their
      relevance for clinical practice.
AB  - INTRODUCTION: This study assessed KRAS mutation detection and functional
      characteristics across 13 distinct technologies and assays available in clinical
      practice, in a blinded manner. METHODS: Five distinct KRAS-mutant cell lines were
      used to study five clinically relevant KRAS mutations: p.G12C, p.G12D, p.G12V,
      p.G13D and p.Q61H. 50 cell line admixtures with low (50 and 100) mutant KRAS
      allele copies at 20%, 10%, 5%, 1% and 0.5% frequency were processed using
      quantitative PCR (qPCR) (n=3), matrix-assisted laser desorption/ionisation time
      of-flight mass spectrometry (MALDI-TOF) (n=2), next-generation sequencing (NGS)
      (n=6), digital PCR (n=1) and Sanger capillary sequencing (n=1) assays. Important
      performance differences were revealed, particularly assay sensitivity and
      turnaround time. RESULTS: Overall 406/728 data points across all 13 technologies
      were identified correctly. Successful genotyping of admixtures ranged from 0%
      (Sanger sequencing) to 100% (NGS). 5/6 NGS platforms reported similar allelic
      frequency for each sample. One NGS assay detected mutations down to a frequency
      of 0.5% and correctly identified all 56 samples (Oncomine Focus Assay, Thermo
      Fisher Scientific). One qPCR (Idylla, Biocartis) and MALDI-TOF (UltraSEEK, Agena
      Bioscience) assay identified 96% (all 100 copies and 23/25 at 50 copies input)
      and 92% (23/25 at 100 copies and 23/25 at 50 copies input) of samples,
      respectively. The digital PCR assay (KRAS PrimePCR ddPCR, Bio-Rad Laboratories)
      identified 60% (100 copies) and 52% (50 copies) of samples correctly. Turnaround
      time from sample to results ranged from ~2 hours (Idylla CE-IVD) to 2 days
      (TruSight Tumor 15 and Sentosa CE-IVD), to 2 weeks for certain NGS assays; the
      level of required expertise ranged from minimal (Idylla CE-IVD) to high for some
      technologies. DISCUSSION: This comprehensive parallel assessment used high
      molecular weight cell line DNA as a model system to address key questions for a
      laboratory when implementing routine KRAS testing. As most of the technologies
      are available for additional molecular biomarkers, this study may be informative
      for other applications.

PMID- 29018578
TI  - The care of adolescents and young adults with cancer: results of the ESMO/SIOPE
      survey.
AB  - INTRODUCTION: Adolescents and young adults (AYA) with cancer require dedicated
      clinical management and care. Little is known about the training and practice of
      European healthcare providers in regard to AYA and the availability of
      specialised services. METHODS: A link to an online survey was sent to members of
      the European Society for Medical Oncology (ESMO) and the European Society for
      Paediatric Oncology (SIOPE). The link was also sent to ESMO National
      Representatives and circulated to other European oncology groups. Questions
      covered the demographics and clinical training of respondents, their definition
      of AYA, education about AYA cancer, access to specialised clinical and supportive
      care, research and further education. Data from Europe were analysed by region.
      RESULTS: Three hundred tweenty two questionnaires were submitted and we focused
      on data from the 266 European healthcare professionals. Responses revealed
      considerable variation both within and between countries in the definition of
      AYA. Over two-thirds of respondents did not have access to specialised centres
      for AYA (67%), were not aware of research initiatives focusing on AYA with cancer
      (69%) and had no access to specialist services for managing the late effects of
      treatment (67%). The majority of the respondents were able to refer AYA patients
      to professional psychological support and specialised social workers. However,
      more than half had no access to an age-specialised nurse or specialised AYA
      education. Overall, 38% of respondents reported that their AYA patients did not
      have access to fertility specialists. This figure was 76% in Eastern Europe. Lack
      of specialised AYA care was particularly evident in Eastern and South-Eastern
      Europe. CONCLUSION: There is important underprovision and inequity of AYA cancer
      care across Europe. Improving education and research focused on AYA cancer care
      should be a priority.

PMID- 29018579
TI  - TAS-102 and the quest for predictive biomarkers.

PMID- 29018580
TI  - A systematic review of cost-effectiveness, comparing traction to intramedullary
      nailing of femoral shaft fractures, in the less economically developed context.
AB  - INTRODUCTION: Femoral shaft fractures carry considerable morbidity and are
      increasingly common in less economically developed countries (LEDCs). Treatment
      options include traction and intramedullary (IM) nailing but in a limited
      resource environment; cost-effectiveness is fundamental to policy development.
      The objective herein was to evaluate the cost-effectiveness of moving from
      traction to IM nailing for femoral shaft fractures, in adults, in LEDCs.
      Incorporating a systematic review of complications and functional outcomes and a
      cost-minimization analysis. METHODS: PubMed, EMBASE, Africa Journals Online and
      the Cochrane Library were searched from inception using the terms: femur* AND
      fracture AND traction AND (sign OR nail* OR intramedullary) AND (cost
      effectiveness OR cost* OR outcome OR function) NOT paed* NOT child* NOT elastic
      NOT neck NOT intertrochanteric NOT periprosthetic (where asterisks indicate an
      unlimited truncation strategy). Abstracts were reviewed for all titles returned
      and full texts obtained as indicated. References of all relevant papers were also
      examined for further studies. RESULTS: IM nailing has been successfully used in
      several institutions and reported infection, union and reoperation rates are
      encouraging, although no randomised control trials were identified. Three studies
      assessed the cost aspect and all found IM nailing to be the cheaper strategy.
      CONCLUSION: To date, the improved complication profile and reduced cost of
      treatment suggest that IM nailing is more cost-effective than traction. Evidence,
      however, is limited and the necessity for appropriate training and audit with the
      introduction of new techniques must be emphasised.

PMID- 29018581
TI  - Cost-effectiveness of diagnostic-therapeutic strategies for paediatric visceral
      leishmaniasis in Morocco.
AB  - INTRODUCTION: Visceral leishmaniasis (VL) is a neglected parasitic disease with a
      high fatality rate if left untreated. Endemic in Morocco, as well as in other
      countries in the Mediterranean basin, VL mainly affects children living in rural
      areas. In Morocco, the direct observation of Leishmania parasites in bone marrow
      (BM) aspirates is used to diagnose VL and meglumine antimoniate (SB) is the first
      line of treatment. Less invasive, more efficacious and safer alternatives exist.
      In this study we estimate the cost-effectiveness of alternative diagnostic
      therapeutic algorithms for paediatric VL in Morocco. METHODS: A decision tree was
      used to estimate the cost-effectiveness of using BM or rapid diagnostic tests
      (RDTs) as diagnostic tools and/or SB or two liposomal amphotericin B (L-AmB)
      regimens: 6-day and 2-day courses to treat VL. Incremental cost-effectiveness
      ratios, expressed as cost per death averted, were estimated by comparing costs
      and effectiveness of the alternative algorithms. A threshold analysis evaluated
      at which price L-AmB became cost-effective compared with current practices.
      RESULTS: Implementing RDT and/or L-AmB treatments would be cost-effective in
      Morocco according to the WHO thresholds. Introducing the 6-day course L-AmB,
      current second-line treatment, would be highly cost-effective if L-AmB price was
      below US$100/phial. The 2-day L-AmB treatment, current standard treatment of
      paediatric VL in France, is highly cost-effective, with L-AmB at its market price
      (US$165/phial). CONCLUSIONS: The results of this study should encourage the
      implementation of RDT and/or short-course L-AmB treatments for paediatric VL
      management in Morocco and other North African countries.

PMID- 29018582
TI  - Effect of low-dose versus higher-dose antenatal iron supplementation on child
      health outcomes at 36 months of age in Viet Nam: longitudinal follow-up of a
      cluster randomised controlled trial.
AB  - INTRODUCTION: Intermittent iron-folic acid supplementation (IFA) is currently
      recommended for pregnant women in populations where anaemia prevalence among
      pregnant women is <20% or if daily iron is not acceptable. The effect of
      providing lower doses of antenatal elemental iron through intermittent regimes on
      longer-term health outcomes in childhood is unclear. METHODS: A prospective
      cohort study conducted between May 2012 and May 2014 in Viet Nam among children
      of 36 months of age, born to women previously enrolled in a cluster randomised
      controlled trial of antenatal micronutrient supplementation (daily IFA (60 mg
      elemental iron) vs twice-weekly IFA (60 mg elemental iron) vs twice-weekly
      multiple micronutrient (MMN) supplementation (60 mg elemental iron)). Primary
      outcomes were height-for-age z-scores (HAZ), according to WHO growth standards
      and cognitive composite scores (Bayley Scales of Infant and Toddler Development,
      third edition) at 36 months of age. RESULTS: A total of 1017 children born to
      mothers enrolled in the cluster randomised trial were assessed at 36 months of
      age. Adjusted mean differences (MDs) in HAZ were -0.14 (95% CI -0.28 to -0.01)
      and -0.15 (95% CI -0.29 to -0.01) in children born to mothers who received twice
      weekly IFA or MMN compared with those who received daily IFA. Children born to
      mothers who received twice-weekly MMN had lower composite motor scores compared
      with those who received daily IFA (MD -2.07, 95% CI -4.11 to -0.03). There were
      no differences in composite cognitive scores in the twice-weekly compared with
      daily regimens. CONCLUSIONS: Low-dose antenatal IFA supplementation (120 mg
      elemental iron per week) resulted in lower HAZ and motor composite scores in
      children compared with higher-dose antenatal IFA supplementation (420 mg
      elemental iron per week). This highlights the importance of adequate iron stores
      during pregnancy and the need for careful monitoring when lower-dose antenatal
      iron regimens are used. TRIAL REGISTRATION NUMBER: Australia New Zealand Clinical
      Trials Registry: 12610000944033.

PMID- 29018584
TI  - Affordability of comprehensive community health worker programmes in rural sub
      Saharan Africa.
AB  - INTRODUCTION: Community health worker (CHW) programmes have low costs per person
      served and are central to achieving universal healthcare. However, their total
      cost is high and the target of one million CHWs for sub-Saharan Africa by 2015
      was not met. We consider the affordability of rural CHW programmes by estimating
      total programme costs relative to national healthcare expenditure at different
      CHW salaries and resources available for healthcare. METHODS: We combine an
      existing source of rural CHW programme costs with World Bank data to estimate
      relative CHW programme costs in 37 countries. We consider three 'salaries' (CHWs
      as volunteers, paid the local equivalent of US$80 per month and paid the national
      minimum wage) and four potential healthcare budgets (both actual and Abuja
      declaration allocations alone and increased by external funding received and
      potential foreign aid, respectively). Costs are shown in 2012 nominal US$.
      RESULTS: With CHWs paid the local equivalent of US$80 per month and financed from
      existing central government healthcare budgets, the median relative cost of a CHW
      programme would be 27% of the healthcare budget. While less than 2.5% in five
      countries (Botswana, Equatorial Guinea, Gabon, Namibia and South Africa), this
      relative cost would exceed 100% in three (Chad, Eritrea and Niger). There is a
      strong negative linear relationship (R2=0.83, p<0.001) between the natural logs
      of gross domestic product (GDP) per capita and affordability. In 23 countries
      with GDP per capita under US$1200, the cost of a CHW programme would exceed 12%
      of actual healthcare spending if CHWs were paid US$80 per month. CONCLUSION: CHWs
      may be a stepping stone to universal access to professional healthcare, but there
      is high variability in the affordability of CHW programmes across sub-Saharan
      Africa. In many countries, such programmes are not yet affordable unless
      significant foreign aid is received.

PMID- 29018583
TI  - Effects of nutrition interventions during pregnancy on low birth weight: an
      overview of systematic reviews.
AB  - INTRODUCTION: Low birth weight (LBW, birth weight less than 2500 g) is associated
      with infant mortality and childhood morbidity. Poor maternal nutritional status
      is one of several contributing factors to LBW. We systematically reviewed the
      evidence for nutrition-specific (addressing the immediate determinants of
      nutrition) and nutrition-sensitive (addressing the underlying cause of
      undernutrition) interventions to reduce the risk of LBW and/or its components:
      preterm birth (PTB) and small-for-gestational age (SGA). METHODS: We conducted a
      comprehensive literature search in MEDLINE, EMBASE, CINAHL and the Cochrane
      Database of Systematic Reviews (September 2015). Systematic reviews of randomised
      controlled trials focusing on nutritional interventions before and during
      pregnancy to reduce LBW and its components were eligible for inclusion into the
      overview review. We assessed the methodological quality of the included reviews
      using A Measurement Tool to Assess Reviews (AMSTAR), PROSPERO: CRD42015024814.
      RESULTS: We included 23 systematic reviews which comprised 34 comparisons.
      Sixteen reviews were of high methodological quality, six of moderate and only one
      review of low quality. Six interventions were associated with a decreased risk of
      LBW: oral supplementation with (1) vitamin A, (2) low-dose calcium, (3) zinc, (4)
      multiple micronutrients (MMN), nutritional education and provision of preventive
      antimalarials. MMN and balanced protein/energy supplementation had a positive
      effect on SGA, while high protein supplementation increased the risk of SGA. High
      dose calcium, zinc or long-chain n-3 fatty acid supplementation and nutritional
      education decreased the risk of PTB. CONCLUSION: Improving women's nutritional
      status positively affected LBW, SGA and PTB. Based on current evidence,
      especially MMN supplementation and preventive antimalarial drugs during pregnancy
      may be considered for policy and practice. However, for most interventions
      evidence was derived from a small number of trials and/or participants. There is
      a need to further explore the evidence of nutrition-specific and nutrition
      sensitive interventions in order to reach the WHO's goal of a 30% reduction in
      the global rate of LBW by 2025.

PMID- 29018585
TI  - Disentangling age-gender interactions associated with risks of fatal and non
      fatal road traffic injuries in the Sultanate of Oman.
AB  - OBJECTIVE: Road traffic injuries (RTIs) are the leading cause of disability
      adjusted life years lost in Oman, Saudi Arabia and United Arab Emirates. Injury
      prevention strategies often overlook the interaction of individual and
      behavioural risk factors in assessing the severity of RTI outcomes. We conducted
      a systematic investigation of the underlying interactive effects of age and
      gender on the severity of fatal and non-fatal RTI outcomes in the Sultanate of
      Oman. METHODS: We used the Royal Oman Police national database of road traffic
      crashes for the period 2010-2014. Our study was based on 35 785 registered
      incidents: of these, 10.2% fatal injuries, 6.2% serious, 27.3% moderate, 37.3%
      mild injuries and 19% only vehicle damage but no human injuries. We applied a
      generalised ordered logit regression to estimate the effect of age and gender on
      RTI severity, controlling for risk behaviours, personal characteristics, vehicle,
      road, traffic, environment conditions and geographical location. RESULTS: The
      most dominant group at risk of all types of RTIs was young male drivers. The
      probability of severe incapacitating injuries was the highest for drivers aged 25
      29 (26.6%) years, whereas the probability of fatal injuries was the highest for
      those aged 20-24 (26.9%) years. Analysis of three-way interactions of age, gender
      and causes of crash show that overspeeding was the primary cause of different
      types of RTIs. In particular, the probability of fatal injuries among male
      drivers attributed to overspeeding ranged from 3%-6% for those aged 35 years and
      above to 13.4% and 17.7% for those aged 25-29 years and 20-24 years,
      respectively. CONCLUSIONS: The high burden of severe and fatal RTIs in Oman was
      primarily attributed to overspeed driving behaviour of young male drivers in the
      20-29 years age range. Our findings highlight the critical need for designing
      early gender-sensitive road safety interventions targeting young male and female
      drivers.

PMID- 29018586
TI  - Sex practices and awareness of Ebola virus disease among male survivors and their
      partners in Guinea.
AB  - INTRODUCTION: Towards the end of the 2013-2016 West African outbreak, sexually
      transmitted Ebola virus re-emerged from Ebola virus disease (EVD) survivors in
      all three hardest hit countries. We explore sex practices and awareness of the
      risk of Ebola virus transmission among EVD survivors and their partners. METHODS:
      In this cross-sectional study, we recruited a convenience sample of study
      participants aged >15 years who were male EVD survivors, their sexual partners
      and a comparison group. We administered a questionnaire to all respondents,
      estimated self-reported sexual practices and risk awareness and conducted in
      depth interviews. RESULTS: We recruited 234 EVD survivors, 256 sexual partners of
      survivors and 65 individuals in the comparison group from five prefectures in
      Guinea. The prevalence of safe sexual behaviour (regular condom use or sexual
      abstinence >12 months) and regular condom use in EVD survivors was 38% (95% CI
      31% to 44%) and 21% (95% CI 16% to 27%), respectively. Among partners, these
      prevalences were lower (11%, 95% CI 7% to 15% and 9%, 95% CI 5% to 12%,
      respectively). EVD survivors were more than five times as likely to engage in
      safe sexual behaviour compared with the comparison group (aOR 5.59, 95% CI 2.36
      to 13.2). One-hundred and thirty one EVD survivors (57%) and 94 partners (37%)
      were aware of the risk of Ebola virus re-emergence associated with having unsafe
      sex. Partners who reported not being informed by their husband/boyfriend (EVD
      survivor) were more likely to be unaware of this risk (aOR 20.5, 95% CI 8.92 to
      47.4). CONCLUSIONS: We disclose here a need to improve knowledge of the disease
      and close the gap between knowledge and practice found in EVD survivors and their
      partners. Current and future survivors' follow-up programmes should include
      partners and be more effective at communicating sex-related risks. Community
      level fears and attitudes that enable stigmatisation should be addressed. Safe
      sex interventions targeting EVD survivors and their partners should be
      prioritised.

PMID- 29018587
TI  - Closing the blood pressure gap: an affordable proposal to save lives worldwide.

PMID- 29018588
TI  - Do chain pharmacies perform better than independent pharmacies? Evidence from a
      standardised patient study of the management of childhood diarrhoea and suspected
      tuberculosis in urban India.
AB  - INTRODUCTION: Pharmacies and drug stores are frequently patients' first point of
      care in many low-income and middle-income countries, but their practice is often
      poor. Pharmacy retailing in India has traditionally been dominated by local,
      individually owned shops, but recent years have seen the growth of pharmacy
      chains. In theory, lower-powered profit incentives and self-regulation to
      preserve brand identity may lead to higher quality in chain stores. In practice,
      this has been little studied. METHODS: We randomly selected a stratified sample
      of chain and independent pharmacies in urban Bengaluru. Standardised patients
      (SPs) visited pharmacies and presented a scripted case of diarrhoea for a child
      and suspected tuberculosis (TB). SPs were debriefed immediately after the visit
      using a structured questionnaire. We measured the quality of history taking,
      therapeutic management and advice giving against national (Government of India)
      and international (WHO) guidelines. We used Pearson's chi2 tests to examine
      associations between pharmacy type and case management. FINDINGS: Management of
      childhood diarrhoea and suspected TB was woefully substandard. History taking of
      the SP was limited; unnecessary and harmful medicines, including antibiotics,
      were commonly sold; and advice giving was near non-existent. The performance of
      chains and independent shops was strikingly similar for most areas of assessment.
      We observed no significant differences between the management of suspected TB in
      chains and independents. 43% of chains and 45% of independents managed the TB
      case correctly; 17% and 16% of chains and independents, respectively, sold
      antibiotics. We found that chains sold significantly fewer harmful antibiotics
      and antidiarrhoeals (35% vs 48%, p=0.029) and prescription-only medicines (37% vs
      49%, p=0.048) for the patient with diarrhoea compared with independent shops. Not
      a single shop managed the patient with diarrhoea correctly according to
      guidelines. CONCLUSION: Our results from Bengaluru suggest that it is unlikely
      that chains alone can solve persisting quality challenges. However, they may
      offer a potential vehicle through which to deliver interventions. Future
      intervention research should consider recruiting chains to see whether
      effectiveness of interventions differ among chains compared with independents.

PMID- 29018589
TI  - Neurological Complications in a Polynesian Traveler with Dengue.
AB  - In recent times, there has been an increased focus on mosquito-borne
      Flaviviruses, in particular dengue and Zika. With the reappearance of dengue in
      Hawai'i and the mainland United States (US), clinicians should be aware of both
      the common presentations of dengue, as well as other less common complications
      associated with the disease. Dengue can result in neurologic disorders such as
      encephalopathy, encephalitis, immune-mediated syndromes, neuromuscular
      dysfunction, and neuro-ophthalmologic disorders. We present an interesting case
      of dengue that initially presented with classic symptoms (arthropathy, biphasic
      fever, and rash) and subsequently developed into a neurologic movement disorder
      with muscle tightening and twitching of the face, chest, and extremities. We
      review and update the epidemiology, biology, the clinical presentations including
      the neurologic complications associated with dengue, as well as their management
      and areas of future study in this field.

PMID- 29018591
TI  - Medical School Hotline: John A. Burns School of Medicine Receives Continued Full
      Accreditation by the Liaison Committee on Medical Education (LCME) for the
      Maximum Accreditation Period of Eight Years.

PMID- 29018590
TI  - Key Factors in Obstetric Delivery Decision-Making among Asian and Pacific
      Islander Women by English Proficiency.
AB  - Childbirth is the most common reason women are hospitalized in the United States.
      Understanding (1) how expectant mothers gather information to decide where to
      give birth, and (2) who helps make that decision, provides critical health
      communication and decision-making insights. Diverse Asian American and Pacific
      Islander (AA/PI) perspectives on such topics are understudied, particularly among
      those with limited English proficiency (LEP). LEP is defined as having a limited
      ability to read, write, speak, or understand English. To address this research
      gap, we interviewed 400 women (18+ years) with a recent live birth on O'ahu,
      Hawai'i. Participants completed a 1-hour, in-person interview in English (n=291),
      Tagalog (n=42), Chinese (n=36), or Marshallese (n=31). Women were asked (1) what
      information was most important in deciding where to deliver and why; and (2) who
      participated in the decision-making and why. Responses were compared by LEP
      (n=71; 18%) vs English-proficient (n=329; 82%) in qualitative and quantitative
      analyses. Both LEP and English-proficient participants reported their
      obstetrician as the most important source of health information. Significantly
      more LEP participants valued advice from family or acquaintances as important
      sources of information compared to English-proficient participants. The top three
      health decision-makers for both those with LEP and English-proficient
      participants were themselves, their obstetrician, and their spouse, which did not
      differ significantly by language proficiency. These findings provide insights
      into health information sources and decision-making across diverse AA/PI
      populations, including those with LEP, and can help direct health interventions
      such as disseminating patient education and healthcare quality information.

PMID- 29018592
TI  - Insights in Public Health: Project Laulima: Expanding Hawai'i's System of Care to
      Better Serve Children and Youth with Co-occurring Mental Health Needs and
      Intellectual/Developmental Disabilities and their Families.

PMID- 29018594
TI  - Comparative study of Cd uptake and tolerance of two Italian ryegrass (Lolium
      multiflorum) cultivars.
AB  - Cadmium (Cd) is one of the most toxic heavy metals and is difficult to be removed
      from contaminated soil and water. Italian ryegrass (Lolium multiflorum), as an
      energy crop, exhibits a valuable potential to develop Cd polluted sites due to
      its use as a biofuel rather than as food and forage. Previously, via a screening
      for Cd-tolerant ryegrass, the two most extreme cultivars (IdyII and Harukaze)
      with high and low Cd tolerance during seed germination, respectively, were
      selected. However, the underlying mechanism for Cd tolerance was not well
      investigated. In this study, we comparatively investigated the growth,
      physiological responses, and Cd uptake and translocation of IdyII and Harukaze
      when the seedlings were exposed to a Cd (0-100 MUM) solution for 12 days. As
      expected, excess Cd inhibited seedling growth and was accompanied by an
      accumulation of malondialdehyde (MDA) and reduced photosynthetic pigments in both
      cultivars. The effects of Cd on the uptake and translocation of other nutrient
      elements (Zn, Fe, Mn and Mg) were dependent on Cd concentrations, cultivars,
      plant tissues and elements. Compared with Harukaze, IdyII exhibited better
      performance with less MDA and higher pigment content. Furthermore, IdyII was less
      efficient in Cd uptake and translocation compared to Harukaze, which might be
      explained by the higher non-protein thiols content in its roots. Taken together,
      our data indicate that IdyII is more tolerant than Harukaze, which partially
      resulted from the differences in Cd uptake and translocation.

PMID- 29018595
TI  - Assessing the living and dead proportions of cold-water coral colonies:
      implications for deep-water Marine Protected Area monitoring in a changing ocean.
AB  - Coral growth patterns result from an interplay of coral biology and environmental
      conditions. In this study colony size and proportion of live and dead skeletons
      in the cold-water coral (CWC) Lophelia pertusa (Linnaeus, 1758) were measured
      using video footage from Remotely Operated Vehicle (ROV) transects conducted at
      the inshore Mingulay Reef Complex (MRC) and at the offshore PISCES site (Rockall
      Bank) in the NE Atlantic. The main goal of this paper was to explore the
      development of a simple method to quantify coral growth and its potential
      application as an assessment tool of the health of these remote habitats.
      Eighteen colonies were selected and whole colony and dead/living layer size were
      measured. Live to dead layer ratios for each colony were then determined and
      analysed. The age of each colony was estimated using previously published data.
      Our paper shows that: (1) two distinct morphotypes can be described: at the MRC,
      colonies displayed a 'cauliflower-shaped' morphotype whereas at the PISCES site,
      colonies presented a more flattened 'bush-shaped' morphotype; (2) living layer
      size was positively correlated with whole colony size; (3) live to dead layer
      ratio was negatively correlated to whole colony size; (4) live to dead layer
      ratio never exceeded 0.27. These results suggest that as a colony develops and
      its growth rate slows down, the proportion of living polyps in the colony
      decreases. Furthermore, at least 73% of L. pertusa colonies are composed of
      exposed dead coral skeleton, vulnerable to ocean acidification and the associated
      shallowing of the aragonite saturation horizon, with significant implications for
      future deep-sea reef framework integrity. The clear visual contrast between
      white/pale living and grey/dark dead portions of the colonies also gives a new
      way by which they can be visually monitored over time. The increased use of
      marine autonomous survey vehicles offers an important new platform from which
      such a surveying technique could be applied to monitor deep-water marine
      protected areas in the future.

PMID- 29018596
TI  - A preliminary survey of zoantharian endosymbionts shows high genetic variation
      over small geographic scales on Okinawa-jima Island, Japan.
AB  - Symbiotic dinoflagellates (genus Symbiodinium) shape the responses of their host
      reef organisms to environmental variability and climate change. To date, the
      biogeography of Symbiodinium has been investigated primarily through phylogenetic
      analyses of the ribosomal internal transcribed spacer 2 region. Although the
      marker can approximate species-level diversity, recent work has demonstrated that
      faster-evolving genes can resolve otherwise hidden species and population
      lineages, and that this diversity is often distributed over much finer
      geographical and environmental scales than previously recognized. Here, we use
      the noncoding region of the chloroplast psbA gene (psbAncr) to examine genetic
      diversity among clade C Symbiodinium associating with the common reef zoantharian
      Palythoa tuberculosa on Okinawa-jima Island, Japan. We identify four closely
      related Symbiodinium psbAncr lineages including one common generalist and two
      potential specialists that appear to be associated with particular microhabitats.
      The sea surface temperature differences that distinguish these habitats are
      smaller than those usually investigated, suggesting that future biogeographic
      surveys of Symbiodinium should incorporate fine scale environmental information
      as well as fine scale molecular data to accurately determine species diversity
      and their distributions.

PMID- 29018597
TI  - Harnessing mtDNA variation to resolve ambiguity in 'Redfish' sold in Europe.
AB  - Morphology-based identification of North Atlantic Sebastes has long been
      controversial and misidentification may produce misleading data, with cascading
      consequences that negatively affect fisheries management and seafood labelling.
      North Atlantic Sebastes comprises of four species, commonly known as 'redfish',
      but little is known about the number, identity and labelling accuracy of redfish
      species sold across Europe. We used a molecular approach to identify redfish
      species from 'blind' specimens to evaluate the performance of the Barcode of Life
      (BOLD) and Genbank databases, as well as carrying out a market product accuracy
      survey from retailers across Europe. The conventional BOLD approach proved
      ambiguous, and phylogenetic analysis based on mtDNA control region sequences
      provided a higher resolution for species identification. By sampling market
      products from four countries, we found the presence of two species of redfish (S.
      norvegicus and S. mentella) and one unidentified Pacific rockfish marketed in
      Europe. Furthermore, public databases revealed the existence of inaccurate
      reference sequences, likely stemming from species misidentification from previous
      studies, which currently hinders the efficacy of DNA methods for the
      identification of Sebastes market samples.

PMID- 29018599
TI  - Qualitative study of healthcare providers' current practice patterns and barriers
      to successful rehydration for pediatric diarrheal illnesses in Kenya.
AB  - BACKGROUND: For children worldwide, diarrhea is the second leading cause of
      death. These deaths are preventable by fluid resuscitation. Nasogastric tubes
      (NGs) have been shown to be equivalent to intravenous fluids for rehydration and
      recommended by the World Health Organization (WHO) for use in severe dehydration.
      Despite this, NGs are rarely used for rehydration in Kenya. Our objective was to
      evaluate clinicians' adherence to rehydration guidelines and to identify barriers
      to the use of NGs for resuscitating dehydrated children. METHODS: A case-based
      structured survey was administered to pediatric care providers in western Kenya
      to determine their choices for alternative rehydration therapies when oral
      rehydration and intravenous fluids fail. Providers then participated in a
      qualitative, semi-structured interview to identify barriers to using nasogastric
      tubes for rehydration. Analysis included manual, progressive coding of interview
      transcripts to identify emerging central themes. RESULTS: Of 44 participants,
      only four (9%) followed WHO guidelines that recommend quickly switching to NG for
      rehydration in their case responses. Participants identified that placing
      intravenous lines in dehydrated children is a challenge. However, when discussing
      NG use, many believed NGs are not effective for rehydration. Other participants'
      concerns surrounded knowledge and training regarding guidelines as well as not
      having NGs available. DISCUSSION: Healthcare providers in western Kenya do not
      report using NGs for rehydration in accordance with WHO guidelines for diarrheal
      illness with severe dehydration. Barriers to the use of NG tubes were lack of
      knowledge and availability. Education and implementation of guidelines using NG
      tubes for rehydration may improve outcomes of children suffering from diarrheal
      illness with severe dehydration.

PMID- 29018600
TI  - Diverse responses of Symbiodinium types to menthol and DCMU treatment.
AB  - To understand the mechanism of photosynthetic inhibition and generation of
      reactive oxygen species (ROS) in Symbiodinium types under stress, chemicals such
      as dichlorophenyl dimethylurea (DCMU) are widely used. Moreover, DCMU and
      recently menthol were used to generate aposymbiotic cnidarian hosts. While the
      effects of DCMU on Symbiodinium cells have been extensively studied, no studies
      have shown the mechanism behind menthol-induced coral bleaching. Moreover, no
      study has compared the effects of DCMU and menthol treatments on photosystem II
      (PSII) activity and generation of ROS in different Symbiodinium types. In this
      study, we utilized five freshly isolated Symbiodinium types (S. minutum (B1), S.
      goreaui (C1), C3, C15, and S. trenchii (D1a)) to compare the effects of DCMU and
      menthol treatments. Symbiodinium cells were exposed to DCMU and menthol at
      different concentrations for 4 h. Results showed that values of the 50%
      inhibitory concentration (IC50) for PSII inhibition were 0.72~1.96 mM for menthol
      treated cells compared to 29~74 pM for DCMU-treated cells. Diverse responses of
      Symbiodinium types were displayed in terms of PSII tolerance to menthol (S.
      minutum > S. trenchii = C15 > C3 = S. goreaui), and also in the response curves.
      In contrast, responses were not so diverse when the different types were treated
      with DCMU. Three of five menthol-treated Symbiodinium types showed instant and
      significant ROS generation when PSII activity was inhibited, compared to no ROS
      being generated in DCMU-treated Symbiodinium types. Both results indicated that
      menthol inhibited Symbiodinium PSII activity through Symbiodinium type-dependent
      mechanisms, which were also distinct from those with DCMU treatment. This study
      further confirmed that photosynthetic functions Symbiodinium have diverse
      responses to stress even within the same clade.

PMID- 29018601
TI  - Sensory determinants of the autonomous sensory meridian response (ASMR):
      understanding the triggers.
AB  - The autonomous sensory meridian response (ASMR) is an atypical sensory phenomenon
      involving electrostatic-like tingling sensations in response to certain sensory,
      primarily audio-visual, stimuli. The current study used an online questionnaire,
      completed by 130 people who self-reported experiencing ASMR. We aimed to extend
      preliminary investigations into the experience, and establish key multisensory
      factors contributing to the successful induction of ASMR through online media.
      Aspects such as timing and trigger load, atmosphere, and characteristics of ASMR
      content, ideal spatial distance from various types of stimuli, visual
      characteristics, context and use of ASMR triggers, and audio preferences are
      explored. Lower-pitched, complex sounds were found to be especially effective
      triggers, as were slow-paced, detail-focused videos. Conversely, background music
      inhibited the sensation for many respondents. These results will help in
      designing media for ASMR induction.

PMID- 29018598
TI  - The Plasmodium berghei RC strain is highly diverged and harbors putatively novel
      drug resistance variants.
AB  - BACKGROUND: The current first line drugs for treating uncomplicated malaria are
      artemisinin (ART) combination therapies. However, Plasmodium falciparum parasites
      resistant to ART and partner drugs are spreading, which threatens malaria control
      efforts. Rodent malaria species are useful models for understanding antimalarial
      resistance, in particular genetic variants responsible for cross resistance to
      different compounds. METHODS: The Plasmodium berghei RC strain (PbRC) is
      described as resistant to different antimalarials, including chloroquine (CQ) and
      ART. In an attempt to identify the genetic basis for the antimalarial resistance
      trait in PbRC, its genome was sequenced and compared with five other previously
      sequenced P. berghei strains. RESULTS: We found that PbRC is eight-fold less
      sensitive to the ART derivative artesunate than the reference strain PbANKA. The
      genome of PbRC is markedly different from other strains, and 6,974 single
      nucleotide variants private to PbRC were identified. Among these PbRC private
      variants, non-synonymous changes were identified in genes known to modulate
      antimalarial sensitivity in rodent malaria species, including notably the
      ubiquitin carboxyl-terminal hydrolase 1 gene. However, no variants were found in
      some genes with strong evidence of association with ART resistance in P.
      falciparum such as K13 propeller protein. DISCUSSION: The variants identified in
      PbRC provide insight into P. berghei genome diversity and genetic factors that
      could modulate CQ and ART resistance in Plasmodium spp.

PMID- 29018602
TI  - Elevated serum osteoprotegerin may predict peripheral arterial disease after
      kidney transplantation: a single-center prospective cross-sectional study in
      Taiwan.
AB  - BACKGROUND: Osteoprotegerin (OPG) is a potential biomarker for severity and
      complications of cardiovascular diseases. Peripheral arterial disease (PAD) is
      associated with an increased risk of death in kidney transplantation (KT)
      patients. This prospective cross-sectional study evaluated the relationship
      between serum OPG and PAD in KT patients. METHODS: Seventy-four KT patients were
      enrolled for this PAD study. Fasting blood samples were obtained to measure serum
      OPG levels by using enzyme-linked immunosorbent assay kits. The ankle-brachial
      index (ABI) of less than 0.9 was applied for PAD diagnosis. RESULTS: Thirteen
      patients (17.6%) were diagnosed with PAD. Diabetes (P = 0.025), smoking (P =
      0.010), and increased OPG levels (P = 0.001) were significantly more frequent in
      the PAD group. Multivariate logistic regression analysis showed that serum OPG
      (odds ratio [OR], 1.336; 95% CI [1.108-1.611]; P = 0.002) and diabetes (OR,
      7.120; 95% CI [1.080-46.940]; P = 0.041) were independent predictors of PAD in KT
      patients. The area under the receiver operating characteristic (ROC) curve
      determined that the probability of a serum OPG level of 7.117 pg/L in predicting
      PAD in KT patients was 0.799 (95% CI [0.690-0.884]; P < 0.001). DISCUSSION:
      Exploration of reliable biomarkers for early identification of vascular risk is
      crucial for KT patients. Elevated serum OPG levels may predict PAD in KT patients
      with cutoff value of 7.117 pg/L.

PMID- 29018603
TI  - Assessment on the coupling effects of drip irrigation and organic fertilization
      based on entropy weight coefficient model.
AB  - Water and fertilizer are two important factors influencing crop growth,
      development and yield formation. To investigate their combined effects on the
      soil-plant system, and to find out the optimal water and organic fertilizer
      coupling strategy for tomato (Solanum lycopersicum L), an experiment was carried
      out from May to October in 2016 in the south of China. The experiment consisted
      of three drip irrigation quotas (150, 180, 210 m3/ha) and three organic
      fertilizer application amounts (2,800, 3,600, 4,400 kg/ha). A water-fertilizer
      treatment (abbreviated as CK) that is in line with local practice was used for
      comparison. The tomato marketable yield, sugar/acid ratio (SAR) and irrigation
      water use efficiency (IWUE), as well as the soil salinity and available nutrient
      concentrations were measured. The results showed that the marketable yield was
      highly significantly (p < 0.01) affected by irrigation or fertilization. The SAR
      of tomato were significantly (p < 0.05) affected by irrigation or/and
      fertilization. The fertilization had an highly significant (p < 0.01) effect on
      the concentrations of soil nutrients (N, P, K), while the coupling effect of
      irrigation and fertilization was not pronounced. According to the multi-index
      analysis and the computed result by the entropy weight coefficient model, a 180
      m3/ha irrigation quota in combination with 4,400 kg/ha organic fertilizer
      application amount was the optimal water-fertilizer coupling strategy which owned
      the most satisfactory comprehensive benefits. The marketable yield, SAR and IWUE
      under this optimal strategy were 122.4 t/ha, 9.2, 32.4 kg/m3, respectively, and
      by 28.0%, 29.6% and 28.1% higher compared to that under CK.

PMID- 29018604
TI  - Effects of invasion history on physiological responses to immune system
      activation in invasive Australian cane toads.
AB  - The cane toad (Rhinella marina) has undergone rapid evolution during its invasion
      of tropical Australia. Toads from invasion front populations (in Western
      Australia) have been reported to exhibit a stronger baseline phagocytic immune
      response than do conspecifics from range core populations (in Queensland). To
      explore this difference, we injected wild-caught toads from both areas with the
      experimental antigen lipopolysaccharide (LPS, to mimic bacterial infection) and
      measured whole-blood phagocytosis. Because the hypothalamic-pituitary-adrenal
      axis is stimulated by infection (and may influence immune responses), we measured
      glucocorticoid response through urinary corticosterone levels. Relative to
      injection of a control (phosphate-buffered saline), LPS injection increased both
      phagocytosis and the proportion of neutrophils in the blood. However, responses
      were similar in toads from both populations. This null result may reflect the
      ubiquity of bacterial risks across the toad's invaded range; utilization of this
      immune pathway may not have altered during the process of invasion. LPS injection
      also induced a reduction in urinary corticosterone levels, perhaps as a result of
      chronic stress.

PMID- 29018606
TI  - Exceptional soft tissues preservation in a mummified frog-eating Eocene
      salamander.
AB  - Fossils are almost always represented by hard tissues but we present here the
      exceptional case of a three-dimensionally preserved specimen that was 'mummified'
      (likely between 40 and 34 million years ago) in a terrestrial karstic
      environment. This fossil is the incomplete body of a salamander, Phosphotriton
      sigei, whose skeleton and external morphology are well preserved, as revealed by
      phase-contrast synchrotron X-ray microtomography. In addition, internal
      structures composed of soft tissues preserved in three dimensions are now
      identified: a lung, the spinal cord, a lumbosacral plexus, the digestive tract,
      muscles and urogenital organs that may be cloacal glands. These are among the
      oldest known cases of three-dimensional preservation of these organs in
      vertebrates and shed light on the ecology of this salamander. Indeed, the
      digestive tract contains remains of a frog, which represents the only known case
      of an extinct salamander that fed on a frog, an extremely rare type of predation
      in extant salamanders. These new data improve our scarce knowledge on soft tissue
      anatomy of early urodeles and should prove useful for future biologists and
      palaeontologists working on urodele evolutionary biology. We also suggest that
      the presence of bat guano and carcasses represented a close source of phosphorus,
      favouring preservation of soft tissues. Bone microanatomy indicates that P. sigei
      was likely amphibious or terrestrial, and was probably not neotenic.

PMID- 29018605
TI  - Enhanced conflict monitoring via a short-duration, video-assisted deep breathing
      in healthy young adults: an event-related potential approach through the Go/NoGo
      paradigm.
AB  - OBJECTIVES: Practitioners of mindfulness are reported to have greater cognitive
      control especially in conflict monitoring, response inhibition and sustained
      attention. However, due to the various existing methods in each mindfulness
      practices and also, the high commitment factor, a barrier still exists for an
      individual to pick up the practices. Therefore, the effect of short duration deep
      breathing on the cognitive control is investigated here. METHODS: Short duration
      guided deep breathing videos consisting of 5, 7 and 9 min respectively were
      created and used on subjects training. The effect on cognitive control was
      assessed using a Go/NoGo task along with event-related potential (ERP)
      measurements at Fz, Cz, and Pz. RESULTS: From the study, the significant outcome
      showed at the follow-up session in which participants engaged for 5 min deep
      breathing group showed a profound NoGo N2 amplitude increment as compared to the
      control group, indicating an enhanced conflict monitoring ability. An inverse
      relationship between the NoGo N2 amplitude and the breathing duration is observed
      as well at the follow-up session. CONCLUSION: These results indicated the
      possibility of performing short duration deep breathing guided by a video to
      achieve an enhanced conflict monitoring as an alternative to other mindfulness
      practices and 5 min is found to be the optimum practice duration. SIGNIFICANT:
      This study is the first to establish a relationship between deep breathing and
      conflict monitoring through ERP. The study population of young adults taken from
      the same environment reduces the variance in ERP results due to age and
      environment. LIMITATION: A larger sample size would provide a greater statistical
      power. A longer duration of deep breathing should be investigated to further
      clarify the relationship between the practice duration and the NoGo N2 amplitude.
      The result can be split by gender and analyzed separately due to the different
      brain structure of males and females.

PMID- 29018607
TI  - Effects of astragalus polysaccharide on the adhesion-related immune response of
      endothelial cells stimulated with CSFV in vitro.
AB  - BACKGROUND: Astragalus polysaccharide (APS) has immunomodulatory activities on
      porcine peripheral blood mononuclear cells. The immunomodulatory effects of APS
      on porcine endothelial cells (ECs) expose to classical swine fever virus (CSFV)
      remain unknown. METHODS: The virus was titrated using an indirect immune biotin
      enzyme standard method to confirm that porcine ECs were susceptible to CSFV
      infection and to determine the TCID50 of CSFV (C-strain). Porcine ECs were
      cultured with CSFV in the presence of APS. Relative quantitative PCR was used to
      assess the mRNA expression of factors that influence EC adhesion and immunity.
      RESULTS: The expression of adhesion factors mRNA increased following stimulation
      with CSFV; this effect was inhibited by pre-exposing the cells to APS. In
      addition, the expression of growth factors and some immune factors increased
      after infection with CSFV; this increase in tissue factor (TF), transforming
      growth factor (TGF-beta), and interleukin-8 (IL-8) could be inhibited by the
      addition of APS. The immune response mediated by Toll-like receptor 4 (TLR4) in
      ECs may be unregulated by CSFV as it was also inhibited by pre-treatment with
      APS. DISCUSSION: The addition of APS to the culture can obviously regulate the
      expression of molecules related to the adhesion, growth, and immune response of
      ECs, as well as the production of cytokines. Therefore, it may have the potential
      to be an effective component in vaccines against CSFV.

PMID- 29018608
TI  - Development and validation of near-infrared spectroscopy for the prediction of
      forage quality parameters in Lolium multiflorum.
AB  - Italian ryegrass (Lolium multiflorum) is an important cool-season, annual forage
      crop for the grassland rotation system in Southern China. The primary aim of
      breeding programs is always to seek to improve forage quality in the animal
      productivity system; however, it is time- and labor-consuming when analyzed
      excessive large number of samples. The main objectives of this study were to
      construct near-infrared reflectance spectroscopy (NIRS) models to predict the
      forage chemistry quality of Italian ryegrass including the concentrations of
      crude protein (CP), acid detergent fiber (ADF), neutral detergent fiber (NDF),
      and water soluble carbohydrate (WSC). The results showed that a broader range of
      CP, NDF, ADF and WSC contents (%DM) were obtained (4.45-30.60, 21.29-60.47, 11.66
      36.17 and 3.95-51.52, respectively) from the samples selected for developing NIRS
      models. In addition, the critical wavelengths identified in this study to
      construct optimal NIRS models were located in 4,247-6,102 and 4,247-5,450 cm-1
      for CP and NDF content, and both wavelengths 5,446-6,102 and 4,247-4,602 cm-1
      could for ADF and WSC. Finally, the optimal models were developed based on the
      laboratory data and the spectral information by partial least squares (PLS)
      regression, with relatively high coefficients of determination (R2CV, CP = 0.99,
      NDF = 0.94, ADF = 0.92, WSC = 0.88), ratio of prediction to devitation (RPD, CP =
      8.58, NDF = 4.25, ADF = 3.64, WSC = 3.10). The further statistics of prediction
      errors relative to laboratory (PRL) and the range error ratio (RER) give
      excellent assessments of the models with the PRL ratios lower than 2 and the RER
      values greater than 10. The NIRS models were validated using a completely
      independent set of samples and have coefficients of determination (R2V, CP =
      0.99, NDF = 0.91, ADF = 0.95, WSC = 0.91) and ratio of prediction to deviation
      (RPD, CP = 9.37, NDF = 3.44, ADF = 4.40, WSC = 3.39). The result suggested that
      routine screening for forage quality parameters with large numbers of samples is
      available with the NIRS model in Italian ryegrass breeding programs, as well as
      facilitating graziers to monitor the forage development stage for improving
      grazing efficiency.

PMID- 29018609
TI  - New whaitsioids (Therapsida: Therocephalia) from the Teekloof Formation of South
      Africa and therocephalian diversity during the end-Guadalupian extinction.
AB  - Two new species of therocephalian therapsids are described from the upper Permian
      Teekloof Formation of the Karoo Basin, South Africa. They include two specimens
      of a whaitsiid, Microwhaitsia mendrezi gen. et sp. nov., and a single, small
      whaitsioid Ophidostoma tatarinovi gen. et sp. nov., which preserves a combination
      of primitive and apomorphic features. A phylogenetic analysis of 56 therapsid
      taxa and 136 craniodental and postcranial characters places the new taxa within
      the monophyletic sister group of baurioids-Whaitsioidea-with Microwhaitsia as a
      basal whaitsiid and Ophidostoma as an aberrant whaitsioid just outside the
      hofmeyriid+whaitsiid subclade. The new records support that whaitsioids were
      diverse during the early-late Permian (Wuchiapingian) and that the dichotomy
      between whaitsiid-line and baurioid-line eutherocephalians was established early
      on. The oldest Gondwanan whaitsiid Microwhaitsia and additional records from the
      lower strata of the Teekloof Formation suggest that whaitsioids had diversified
      by the early Wuchiapingian and no later than Pristerognathus Assemblage Zone
      times. Prior extinction estimates based on species counts are reflected in an
      analysis of origination/extinction rates, which imply increasing faunal turnover
      from Guadalupian to Lopingian (late Permian) times. The new records support a
      growing body of evidence that some key Lopingian synapsid clades originated near
      or prior to the Guadalupian-Lopingian boundary ca. 260-259 million years ago, but
      only radiated following the end-Guadalupian extinction of dinocephalians and
      basal therocephalian predators (long-fuse model). Ongoing collecting in older
      portions of the Teekloof Formation (e.g., Pristerognathus Assemblage Zone) will
      shed further light on early eutherocephalians during this murky but critical time
      in their evolutionary diversification.

PMID- 29018610
TI  - Impact of land reclamation and agricultural water regime on the distribution and
      conservation status of the endangered Dryophytes suweonensis.
AB  - Knowledge about the distribution and habitat preferences of a species is critical
      for its conservation. The Suweon Treefrog (Dryophytes suweonensis) is an
      endangered species endemic to the Republic of Korea. We conducted surveys from
      2014 to 2016 at 890 potentially suitable sites across the entire range of the
      species in South Korea. We then assessed whether D. suweonensis was found in the
      current and ancestral predicted ranges, reclaimed and protected areas, and how
      the presence of agricultural floodwater affected its occurrence. Our results
      describe a 120 km increase in the southernmost known distribution of the species,
      and the absence of the species at lower latitudes. We then demonstrate a putative
      constriction on the species ancestral range due to urban encroachment, and
      provide evidence for a significant increase in its coastal range due to the
      colonisation of reclaimed land by the species. In addition, we demonstrate that
      D. suweonensis is present in rice fields that are flooded with water originating
      from rivers as opposed to being present in rice fields that are irrigated from
      underground water. Finally, the non-overlap of protected areas and the occurrence
      of the species shows that only the edge of a single site where D. suweonensis
      occurs is legally protected. Based on our results and the literature, we suggest
      the design of a site fitting all the ecological requirements of the species, and
      suggest the use of such sites to prevent further erosion in the range of D.
      suweonensis.

PMID- 29018611
TI  - Clone wars: asexual reproduction dominates in the invasive range of Tubastraea
      spp. (Anthozoa: Scleractinia) in the South-Atlantic Ocean.
AB  - Although the invasive azooxanthellate corals Tubastraea coccinea and T.
      tagusensis are spreading quickly and outcompeting native species in the Atlantic
      Ocean, there is little information regarding the genetic structure and path of
      introduction for these species. Here we present the first data on genetic
      diversity and clonal structure from these two species using a new set of
      microsatellite markers. High proportions of clones were observed, indicating that
      asexual reproduction has a major role in the local population dynamics and,
      therefore, represents one of the main reasons for the invasion success. Although
      no significant population structure was found, results suggest the occurrence of
      multiple invasions for T. coccinea and also that both species are being
      transported along the coast by vectors such as oil platforms and monobouys,
      spreading these invasive species. In addition to the description of novel
      microsatellite markers, this study sheds new light into the invasive process of
      Tubastraea.

PMID- 29018613
TI  - Relationship between hemoglobin glycation index and extent of coronary heart
      disease in individuals with type 2 diabetes mellitus: a cross-sectional study.
AB  - BACKGROUND: Individuals with type 2 diabetes (T2D) are at an increased risk of
      coronary heart disease (CHD). Diabetic complications have recently been
      associated with a measure of glucose metabolism known as the hemoglobin glycation
      index (HGI). Currently there is insufficient information regarding a potential
      link between HGI and cardiovascular disease. This study aimed to investigate the
      relationship between HGI and extent of CHD in individuals with T2D. METHODS: This
      cross-sectional study screened individuals visiting the endocrinology clinic
      between June 2012 and May 2016 for eligibility. Enrollment criteria included
      individuals above 21 years of age with T2D diagnosed in the preceding ten years.
      Candidates with hemoglobin disorders, pregnancy, and existing coronary artery
      disease were excluded. Fasting plasma glucose (FPG) and glycated hemoglobin A1c
      (HbA1c) were sampled three months prior to angiography. The regression equation
      of predicted HbA1c = 0.008 * FPG + 6.28 described the linear relationship between
      these variables. HGI was calculated as the difference between the measured HbA1c
      and predicted HbA1c. Participants were classified into two groups according to
      the presence of supranormal (>=0) or subnormal HGI (<0). RESULTS: Among 423
      participants, people with supranormal HGI harbored an increased prevalence of
      multiple vessel disease relative to those with subnormal HGI (Odds ratio (OR):
      3.9, 95% CI [2.64-5.98], P < 0.001). Moreover, individuals with supranormal HGI
      more frequently demonstrated lesions involving the left anterior descending
      artery (OR: 3.0, 95% CI [1.97-4.66], P < 0.001). The intergroup difference in
      mean HbA1c was statistically nonsignificant (7.5 +/- 1.0% versus 7.4 +/- 1.1%, P
      = 0.80). DISCUSSION: This study demonstrated that HGI correlated with the extent
      of CHD in individuals with T2D. People with supranormal HGI harbored a higher
      prevalence of extensive cardiovascular disease compared to those with subnormal
      HGI. The relationship between HGI and extent of CHD enables cardiovascular risk
      stratification in at risk individuals. Overall, HGI provides useful information
      concerning cardiovascular risk in clinical practice.

PMID- 29018612
TI  - Segmentation and classification of colon glands with deep convolutional neural
      networks and total variation regularization.
AB  - Segmentation of histopathology sections is a necessary preprocessing step for
      digital pathology. Due to the large variability of biological tissue, machine
      learning techniques have shown superior performance over conventional image
      processing methods. Here we present our deep neural network-based approach for
      segmentation and classification of glands in tissue of benign and malignant
      colorectal cancer, which was developed to participate in the GlaS@MICCAI2015
      colon gland segmentation challenge. We use two distinct deep convolutional neural
      networks (CNN) for pixel-wise classification of Hematoxylin-Eosin stained images.
      While the first classifier separates glands from background, the second
      classifier identifies gland-separating structures. In a subsequent step, a figure
      ground segmentation based on weighted total variation produces the final
      segmentation result by regularizing the CNN predictions. We present both
      quantitative and qualitative segmentation results on the recently released and
      publicly available Warwick-QU colon adenocarcinoma dataset associated with the
      GlaS@MICCAI2015 challenge and compare our approach to the simultaneously
      developed other approaches that participated in the same challenge. On two test
      sets, we demonstrate our segmentation performance and show that we achieve a
      tissue classification accuracy of 98% and 95%, making use of the inherent
      capability of our system to distinguish between benign and malignant tissue. Our
      results show that deep learning approaches can yield highly accurate and
      reproducible results for biomedical image analysis, with the potential to
      significantly improve the quality and speed of medical diagnoses.

PMID- 29018614
TI  - Anti-apoptotic properties of carbon monoxide in porcine oocyte during in vitro
      aging.
AB  - If fertilization of matured oocyte does not occur, unfertilized oocyte undergoes
      aging, resulting in a time-dependent reduction of the oocyte's quality. The aging
      of porcine oocytes can lead to apoptosis. Carbon monoxide (CO), a signal molecule
      produced by the heme oxygenase (HO), possesses cytoprotective and anti-apoptotic
      effects that have been described in somatic cells. However, the effects of CO in
      oocytes have yet to be investigated. By immunocytochemistry method we detected
      that both isoforms of heme oxygenase (HO-1 and HO-2) are present in the porcine
      oocytes. Based on the morphological signs of oocyte aging, it was found that the
      inhibition of both HO isoforms by Zn-protoporphyrin IX (Zn-PP IX) leads to an
      increase in the number of apoptotic oocytes and decrease in the number of intact
      oocytes during aging. Contrarily, the presence of CO donors (CORM-2 or CORM-A1)
      significantly decrease the number of apoptotic oocytes while increasing the
      number of intact oocytes. We also determined that CO donors significantly
      decrease the caspase-3 (CAS-3) activity. Our results suggest that HO/CO
      contributes to the sustaining viability through regulation of apoptosis during in
      vitro aging of porcine oocytes.

PMID- 29018615
TI  - A randomized control trial feasibility evaluation of an mHealth intervention for
      wheelchair skill training among middle-aged and older adults.
AB  - BACKGROUND: Providing mobility skills training to manual wheelchair (MWC) users
      can have a positive impact on community participation, confidence and quality of
      life. Often such training is restricted or not provided at all because of the
      expense of, and limited access to, occupational and physical therapists before
      and after discharge. This is particularly true among middle-aged and older
      adults, who often have limited access to rehabilitation services and require more
      time to learn motor skills. A monitored MWC skills training home program,
      delivered using a computer tablet (mHealth), was developed as an alternative
      approach to service delivery. The purpose of this study was to evaluate the
      feasibility of implementing this mHealth MWC skills training program among middle
      aged and older adults. METHODS: A 2 * 2 factorial design randomized controlled
      trial (RCT) was used to compare the mHealth intervention and control groups, with
      additional wheeling time as a second factor. Community-dwelling MWC users aged 55
      and older, who had used their MWC for less than two years and propelled with two
      hands, were recruited. Feasibility outcomes related to process, resources,
      management and treatment criteria were collected. RESULTS: Eighteen participants
      were recruited, with a retention rate of 94%. Mean (+/-SD) duration for the first
      and second in-person training sessions were 90.1 +/- 20.5 and 62.1 +/- 5.5 min,
      respectively. In the treatment group, 78% achieved the minimum amount of home
      training (i.e., 300 min) over four weeks and 56% achieved the preferred training
      threshold (i.e., 600 min). Trainers reported only seven minor protocol
      deviations. No tablets were lost or damaged and there was one incident of tablet
      malfunction. No injuries or adverse incidents were reported during data
      collection or training activities. Participants indicated 98% agreement on the
      post-treatment benefit questionnaire. DISCUSSION: Overall, the study protocol
      enabled implementation of the intervention in a safe, efficient and acceptable
      manner. Participant recruitment proved to be challenging, particularly gaining
      access to individuals who might benefit. Resource issue demands were acceptable
      for administration of the intervention; data collection was more time-consuming
      than anticipated but could be reduced with minor revisions. Participant retention
      and home program treatment adherence was high; both participant and trainer
      burden was acceptable. Treatment group participants reported a positive
      experience and clinical benefits from training program. The findings suggest a
      full-scale RCT evaluating the clinical impact of the Enhancing Participation In
      the Community by improving Wheelchair Skills (EPIC Wheels) intervention is
      warranted, provided the recruitment issues are addressed through collaborative
      partnerships and active recruitment strategies.

PMID- 29018616
TI  - Integration of lncRNA-miRNA-mRNA reveals novel insights into oviposition
      regulation in honey bees.
AB  - BACKGROUND: The honey bee (Apis mellifera) is a highly diverse species commonly
      used for honey production and pollination services. The oviposition of the honey
      bee queen affects the development and overall performance of the colony. To
      investigate the ovary activation and oviposition processes on a molecular level,
      a genome-wide analysis of lncRNAs, miRNAs and mRNA expression in the ovaries of
      the queens was performed to screen for differentially expressed coding and
      noncoding RNAs. Further analysis identified relevant candidate genes or RNAs.
      RESULTS: The analysis of the RNA profiles in different oviposition phase of the
      queens revealed that 740 lncRNAs, 81 miRNAs and 5,481 mRNAs were differently
      expressed during the ovary activation; 88 lncRNAs, 13 miRNAs and 338 mRNAs were
      differently expressed during the oviposition inhibition process; and finally, 100
      lncRNAs, four miRNAs and 497 mRNAs were differently expressed during the
      oviposition recovery process. In addition, functional annotation of
      differentially expressed RNAs revealed several pathways that are closely related
      to oviposition, including hippo, MAPK, notch, Wnt, mTOR, TGF-beta and FoxO
      signaling pathways. Furthermore, in the QTL region for ovary size, 73
      differentially expressed genes and 14 differentially expressed lncRNAs were
      located, which are considered as candidate genes affecting ovary size and
      oviposition. Moreover, a core set of genes served as bridges among different
      miRNAs were identified through the integrated analysis of lncRNA-miRNA-mRNA
      network. CONCLUSION: The observed dramatic expression changes of coding and
      noncoding RNAs suggest that they may play a critical role in honey bee queens'
      oviposition. The identified candidate genes for oviposition activation and
      regulation could serve as a resource for further studies of genetic markers of
      oviposition in honey bees.

PMID- 29018617
TI  - Perch, Perca fluviatilis show a directional preference for, but do not increase
      attacks toward, prey in response to water-borne cortisol.
AB  - In freshwater environments, chemosensory cues play an important role in predator
      prey interactions. Prey use a variety of chemosensory cues to detect and avoid
      predators. However, whether predators use the chemical cues released by disturbed
      or stressed prey has received less attention. Here we tested the hypothesis that
      the disturbance cue cortisol, in conjunction with visual cues of prey, elevates
      predatory behavior. We presented predators (perch, Perca fluviatilis) with three
      chemosensory choice tests and recorded their location, orientation, and
      aggressive behavior. We compared the responses of predators when provided with
      (i) visual cues of prey only (two adjacent tanks containing sticklebacks); (ii)
      visual and natural chemical cues of prey vs. visual cues only; and (iii) visual
      cues of prey with cortisol vs. visual cues only. Perch spent a significantly
      higher proportion of time in proximity to prey, and orientated toward prey more,
      when presented with a cortisol stimulus plus visual cues, relative to
      presentations of visual and natural chemical cues of prey, or visual cues of prey
      only. There was a trend that perch directed a higher proportion of predatory
      behaviors (number of lunges) toward sticklebacks when presented with a cortisol
      stimulus plus visual cues, relative to the other chemosensory conditions. But
      they did not show a significant increase in total predatory behavior in response
      to cortisol. Therefore, it is not clear whether water-borne cortisol, in
      conjunction with visual cues of prey, affects predatory behavior. Our results
      provide evidence that cortisol could be a source of public information about prey
      state and/or disturbance, but further work is required to confirm this.

PMID- 29018618
TI  - Framework for community functioning: synthesis of stress gradient and resource
      partitioning concepts.
AB  - To understand how communities function and generate abundance, I develop a
      framework integrating elements from the stress gradient and resource partitioning
      concepts. The framework suggests that guild abundance depends on environmental
      and spatial factors but also on inter-guild interactions (competitor or
      facilitator richness), which can alter the fundamental niche of constituent
      species in negative (competition) or positive direction (facilitation).
      Consequently, the environmental and spatial mechanisms driving guild abundance
      would differ across guilds and interaction modes. Using continental data on
      stream diatoms and physico-chemistry, the roles of these mechanisms were tested
      under three interaction modes-shared preference, distinct preference, and
      facilitative, whereby pairs of guilds exhibited, respectively, a dominance
      tolerance tradeoff along a eutrophication gradient, specialization along a pH
      gradient, or a donor-recipient relationship along a nitrogen gradient.
      Representative of the shared preference mode were the motile (dominant) and low
      profile (tolerant) guilds, of the distinct preference mode-the acidophilous and
      alkaliphilous (low profile) guilds, and of the facilitative mode-nitrogen fixers
      (donors) and motile species (recipients). In each mode, the influences of
      environment, space (latitude and longitude), and competitor or facilitator
      richness on guild density were assessed by variance partitioning. Pure
      environment constrained most strongly the density of the dominant, the
      acidophilous, and the recipient guild in the shared preference, distinct
      preference, and facilitative mode, respectively, while spatial effects were
      important only for the low profile guild. Higher competitor richness was
      associated with lower density of the tolerant guild in the shared preference
      mode, both guilds in the distinct preference mode, and the donor guild in the
      facilitative mode. Conversely, recipient density in the facilitative mode
      increased with donor richness in stressful nitrogen-poor environments. Thus,
      diatom guild abundance patterns were determined primarily by biotic and/or
      environmental impacts and, with the exception of the low profile guild, were
      insensitive to spatial effects. This framework identifies major sources of
      variability in diatom guild abundance with implications for the understanding of
      biodiversity-ecosystem functioning.

PMID- 29018619
TI  - Alpha-arylphorin is a mitogen in the Heliothis virescens midgut cell secretome
      upon Cry1Ac intoxication.
AB  - Insecticidal crystal (Cry) proteins produced by the bacterium Bacillus
      thuringiensis (Bt) target cells in the midgut epithelium of susceptible larvae.
      While the mode of action of Cry toxins has been extensively investigated, the
      midgut response to Cry intoxication and its regulation are not well
      characterized. In this work, we describe the secreted proteome (secretome) of
      primary mature midgut cell cultures from Heliothis virescens larvae after
      exposure to Cry1Ac toxin compared to control buffer treatment. The Cry1Ac-induced
      secretome caused higher proliferation and differentiation and an overall
      reduction in total cell mortality over time in primary H. virescens midgut stem
      cell cultures when compared to treatment with control buffer secretome.
      Differential proteomics identified four proteins with significant differences in
      abundance comparing Cry1Ac-treated and control secretomes. The most significant
      difference detected in the Cry1Ac secretome was an arylphorin subunit alpha
      protein not detected in the control secretome. Feeding of purified alpha
      arylphorin to H. virescens larvae resulted in midgut hyperplasia and
      significantly reduced susceptibility to Cry1Ac toxin compared to controls. These
      data identify alpha-arylphorin as a protein with a new putative role in the
      midgut regeneration process in response to Cry1Ac intoxication and possibly
      pathogen/abiotic stress, identifying alpha-arylphorin as a potential gene to
      target with insecticidal gene silencing for pest control.

PMID- 29018621
TI  - The isolation and identification of pathogenic fungi from Tessaratoma papillosa
      Drury (Hemiptera: Tessaratomidae).
AB  - BACKGROUND: Litchi stink-bug, Tessaratoma papillosa Drury (Hemiptera:
      Tessaratomidae), is one of the most widespread and destructive pest species on
      Litchi chinensis Sonn and Dimocarpus longan Lour in Southern China. Inappropriate
      use of chemical pesticides has resulted in serious environmental problems and
      food pollution. Generating an improved Integrated Pest Management (IPM) strategy
      for litchi stink-bug in orchard farming requires development of an effective
      biological control agent. Entomopathogenic fungi are regarded as a vital
      ecological factor in the suppression of pest populations under field conditions.
      With few effective fungi and pathogenic strains available to control litchi stink
      bug, exploration of natural resources for promising entomopathogenic fungi is
      warranted. METHODS & RESULTS: In this study, two pathogenic fungi were isolated
      from cadavers of adult T. papillosa. They were identified as Paecilomyces
      lilacinus and Beauveria bassiana by morphological identification and rDNA-ITS
      homogeneous analysis. Infection of T. papillosa with B. bassiana and P. lilacinus
      occurred initially from the antennae, metameres, and inter-segmental membranes.
      Biological tests showed that the two entomopathogenic fungi induced high
      mortality in 2nd and 5th instar nymphs of T. papillosa. B. bassiana was highly
      virulent on 2nd instar nymphs of T. papillosa, with values for cadaver rate, LC50
      and LT50 of 88.89%, 1.92 * 107 conidia/mL and 4.34 days respectively. DISCUSSION:
      This study provides two valuable entomopathogenic fungi from T. papillosa. This
      finding suggests that the highly virulent P. lilacinus and B. bassiana play an
      important role in the biocontrol of T. papillosa in China. These pathogenic fungi
      had no pollution or residue risk, and could provide an alternative option for IPM
      of litchi stink-bug.

PMID- 29018620
TI  - Mechanisms of action and in vivo antibacterial efficacy assessment of five novel
      hybrid peptides derived from Indolicidin and Ranalexin against Streptococcus
      pneumoniae.
AB  - BACKGROUND: Antimicrobial peptides (AMPs) are of great potential as novel
      antibiotics for the treatment of broad spectrum of pathogenic microorganisms
      including resistant bacteria. In this study, the mechanisms of action and the
      therapeutic efficacy of the hybrid peptides were examined. METHODS: TEM, SEM and
      ATP efflux assay were used to evaluate the effect of hybrid peptides on the
      integrity of the pneumococcal cell wall/membrane. DNA retardation assay was
      assessed to measure the impact of hybrid peptides on the migration of genomic DNA
      through the agarose gel. In vitro synergistic effect was checked using the
      chequerboard assay. ICR male mice were used to evaluate the in vivo toxicity and
      antibacterial activity of the hybrid peptides in a standalone form and in
      combination with ceftriaxone. RESULTS: The results obtained from TEM and SEM
      indicated that the hybrid peptides caused significant morphological alterations
      in Streptococcus pneumoniae and disrupting the integrity of the cell
      wall/membrane. The rapid release of ATP from pneumococcal cells after one hour of
      incubation proposing that the antibacterial action for the hybrid peptides is
      based on membrane permeabilization and damage. The DNA retardation assay revealed
      that at 62.5 ug/ml all the hybrid peptides were capable of binding and preventing
      the pneumococcal genomic DNA from migrating through the agarose gel. In vitro
      synergy was observed when pneumococcal cells treated with combinations of hybrid
      peptides with each other and with conventional drugs erythromycin and
      ceftriaxone. The in vivo therapeutic efficacy results revealed that the hybrid
      peptide RN7-IN8 at 20 mg/kg could improve the survival rate of pneumococcal
      bacteremia infected mice, as 50% of the infected mice survived up to seven days
      post-infection. In vivo antibacterial efficacy of the hybrid peptide RN7-IN8 was
      signficantly improved when combined with the standard antibiotic ceftriaxone at
      (20 mg/kg + 20 mg/kg) as 100% of the infected mice survived up to seven days post
      infection. DISCUSSION: Our results suggest that attacking and breaching the cell
      wall/membrane is most probably the principal mechanism for the hybrid peptides.
      In addition, the hybrid peptides could possess another mechanism of action by
      inhibiting intracellular functions such as DNA synthesis. AMPs could play a great
      role in combating antibiotic resistance as they can reduce the therapeutic
      concentrations of standard drugs.

PMID- 29018622
TI  - Accuracy of microbial community diversity estimated by closed- and open-reference
      OTUs.
AB  - Next-generation sequencing of 16S ribosomal RNA is widely used to survey
      microbial communities. Sequences are typically assigned to Operational Taxonomic
      Units (OTUs). Closed- and open-reference OTU assignment matches reads to a
      reference database at 97% identity (closed), then clusters unmatched reads using
      a de novo method (open). Implementations of these methods in the QIIME package
      were tested on several mock community datasets with 20 strains using different
      sequencing technologies and primers. Richness (number of reported OTUs) was often
      greatly exaggerated, with hundreds or thousands of OTUs generated on Illumina
      datasets. Between-sample diversity was also found to be highly exaggerated in
      many cases, with weighted Jaccard distances between identical mock samples often
      close to one, indicating very low similarity. Non-overlapping hyper-variable
      regions in 70% of species were assigned to different OTUs. On mock communities
      with Illumina V4 reads, 56% to 88% of predicted genus names were false positives.
      Biological inferences obtained using these methods are therefore not reliable.

PMID- 29018623
TI  - voomDDA: discovery of diagnostic biomarkers and classification of RNA-seq data.
AB  - RNA-Seq is a recent and efficient technique that uses the capabilities of next
      generation sequencing technology for characterizing and quantifying
      transcriptomes. One important task using gene-expression data is to identify a
      small subset of genes that can be used to build diagnostic classifiers
      particularly for cancer diseases. Microarray based classifiers are not directly
      applicable to RNA-Seq data due to its discrete nature. Overdispersion is another
      problem that requires careful modeling of mean and variance relationship of the
      RNA-Seq data. In this study, we present voomDDA classifiers: variance modeling at
      the observational level (voom) extensions of the nearest shrunken centroids (NSC)
      and the diagonal discriminant classifiers. VoomNSC is one of these classifiers
      and brings voom and NSC approaches together for the purpose of gene-expression
      based classification. For this purpose, we propose weighted statistics and put
      these weighted statistics into the NSC algorithm. The VoomNSC is a sparse
      classifier that models the mean-variance relationship using the voom method and
      incorporates voom's precision weights into the NSC classifier via weighted
      statistics. A comprehensive simulation study was designed and four real datasets
      are used for performance assessment. The overall results indicate that voomNSC
      performs as the sparsest classifier. It also provides the most accurate results
      together with power-transformed Poisson linear discriminant analysis, rlog
      transformed support vector machines and random forests algorithms. In addition to
      prediction purposes, the voomNSC classifier can be used to identify the potential
      diagnostic biomarkers for a condition of interest. Through this work, statistical
      learning methods proposed for microarrays can be reused for RNA-Seq data. An
      interactive web application is freely available at
      http://www.biosoft.hacettepe.edu.tr/voomDDA/.

PMID- 29018624
TI  - Genome methylation and regulatory functions for hypoxic adaptation in Tibetan
      chicken embryos.
AB  - Tibetan chickens have unique adaptations to the extreme high-altitude environment
      that they inhabit. Epigenetic DNA methylation affects many biological processes,
      including hypoxic adaptation; however, the regulatory genes for DNA methylation
      in hypoxic adaptation remain unknown. In this study, methylated DNA
      immunoprecipitation with high-throughput sequencing (MeDIP-seq) was used to
      provide an atlas of the DNA methylomes of the heart tissue of hypoxic highland
      Tibetan and lowland Chahua chicken embryos. A total of 31.2 gigabases of sequence
      data were generated from six MeDIP-seq libraries. We identified 1,049
      differentially methylated regions (DMRs) and 695 related differentially
      methylated genes (DMGs) between the two chicken breeds. The DMGs are involved in
      vascular smooth muscle contraction, VEGF signaling pathway, calcium signaling
      pathway, and other hypoxia-related pathways. Five candidate genes that had low
      methylation (EDNRA, EDNRB2, BMPR1B, BMPRII, and ITGA2) might play key regulatory
      roles in the adaptation to hypoxia in Tibetan chicken embryos. Our study provides
      significant explanations for the functions of genes and their epigenetic
      regulation for hypoxic adaptation in Tibetan chickens.

PMID- 29018625
TI  - Hearing assessment during deep brain stimulation of the central nucleus of the
      inferior colliculus and dentate cerebellar nucleus in rat.
AB  - BACKGROUND: Recently it has been shown in animal studies that deep brain
      stimulation (DBS) of auditory structures was able to reduce tinnitus-like
      behavior. However, the question arises whether hearing might be impaired when
      interfering in auditory-related network loops with DBS. METHODS: The auditory
      brainstem response (ABR) was measured in rats during high frequency stimulation
      (HFS) and low frequency stimulation (LFS) in the central nucleus of the inferior
      colliculus (CIC, n = 5) or dentate cerebellar nucleus (DCBN, n = 5). Besides
      hearing thresholds using ABR, relative measures of latency and amplitude can be
      extracted from the ABR. In this study ABR thresholds, interpeak latencies (I-III,
      III-V, I-V) and V/I amplitude ratio were measured during off-stimulation state
      and during LFS and HFS. RESULTS: In both the CIC and the CNBN groups, no
      significant differences were observed for all outcome measures. DISCUSSION: DBS
      in both the CIC and the CNBN did not have adverse effects on hearing
      measurements. These findings suggest that DBS does not hamper physiological
      processing in the auditory circuitry.

PMID- 29018626
TI  - Cryptic biodiversity and phylogeographic patterns of Seychellois Ligia isopods.
AB  - Ligia isopods are conspicuous inhabitants of rocky intertidal habitats exhibiting
      several biological traits that severely limit their dispersal potential. Their
      presence in patchy habitats and low vagility may lead to long term isolation,
      allopatric isolation and possible cryptic speciation. Indeed, various species of
      Ligia have been suggested to represent instead cryptic species complexes. Past
      studies; however, have largely focused in Eastern Pacific and Atlantic species of
      Ligia, leaving in doubt whether cryptic diversity occurs in other highly
      biodiverse areas. The Seychelles consists of 115 islands of different ages and
      geological origins spread across the western Indian Ocean. They are well known
      for their rich biodiversity with recent reports of cryptic species in terrestrial
      Seychellois organisms. Despite these studies, it is unclear whether coastal
      invertebrates from the Seychelles harbor any cryptic diversity. In this study, we
      examined patterns of genetic diversity and isolation within Ligia isopods across
      the Seychelles archipelago by characterizing individuals from locations across
      both inner and outer islands of the Seychelles using mitochondrial and nuclear
      markers. We report the presence of highly divergent lineages of independent
      origin. At Aldabra Atoll, we uncovered a lineage closely related to the Ligia
      vitiensis cryptic species complex. Within the inner islands of Cousine,
      Silhouette, and Mahe we detected the presence of two moderately divergent and
      geographically disjunct lineages most closely related to Ligia dentipes. Our
      findings suggest that the Seychelles may harbor at least three novel species of
      Ligia in need of description and that these species may have originated
      independently.

PMID- 29018627
TI  - Independent evolution of tetraloop in enterovirus oriL replicative element and
      its putative binding partners in virus protein 3C.
AB  - BACKGROUND: Enteroviruses are small non-enveloped viruses with a (+) ssRNA genome
      with one open reading frame. Enterovirus protein 3C (or 3CD for some species)
      binds the replicative element oriL to initiate replication. The replication of
      enteroviruses features a low-fidelity process, which allows the virus to adapt to
      the changing environment on the one hand, and requires additional mechanisms to
      maintain the genome stability on the other. Structural disturbances in the apical
      region of oriL domain d can be compensated by amino acid substitutions in
      positions 154 or 156 of 3C (amino acid numeration corresponds to poliovirus 3C),
      thus suggesting the co-evolution of these interacting sequences in nature. The
      aim of this work was to understand co-evolution patterns of two interacting
      replication machinery elements in enteroviruses, the apical region of oriL domain
      d and its putative binding partners in the 3C protein. METHODS: To evaluate the
      variability of the domain d loop sequence we retrieved all available full
      enterovirus sequences (>6, 400 nucleotides), which were present in the NCBI
      database on February 2017 and analysed the variety and abundance of sequences in
      domain d of the replicative element oriL and in the protein 3C. RESULTS: A total
      of 2,842 full genome sequences was analysed. The majority of domain d apical
      loops were tetraloops, which belonged to consensus YNHG (Y = U/C, N = any
      nucleotide, H = A/C/U). The putative RNA-binding tripeptide 154-156 (Enterovirus
      C 3C protein numeration) was less diverse than the apical domain d loop region
      and, in contrast to it, was species-specific. DISCUSSION: Despite the suggestion
      that the RNA-binding tripeptide interacts with the apical region of domain d,
      they evolve independently in nature. Together, our data indicate the plastic
      evolution of both interplayers of 3C-oriL recognition.

PMID- 29018628
TI  - Combined moderate and high intensity exercise with dietary restriction improves
      cardiac autonomic function associated with a reduction in central and systemic
      arterial stiffness in obese adults: a clinical trial.
AB  - OBJECTIVE: The present study aimed to assess the effects of exercise with dietary
      restriction on cardiac autonomic activity, arterial stiffness, and cardiovascular
      biomarkers in obese individuals. METHODS: Seventeen obese adults completed an 8
      week exercise and dietary program. Anthropometry, body composition, and multiple
      biochemical markers were measured. We used carotid-femoral pulse wave velocity
      (cfPWV), brachial-ankle pulse wave velocity (baPWV), central blood pressure, and
      augmentation index (AIx) to assess arterial stiffness. To determine cardiac
      autonomic activity, heart rate variability (HRV) was analyzed by standard
      deviation of normal-to-normal intervals (SDNN), square root of the mean squared
      differences of successive normal-to-normal intervals (RMSSD), total power (TF),
      low-frequency power in normalized units (LFnu), high-frequency power in
      normalized units (HFnu), and low-frequency power/high-frequency power (LF/HF).
      RESULTS: Following the exercise and diet intervention, obese subjects had
      significant reductions in body weight, body mass index, body fat percentage,
      brachial systolic blood pressure, and resting heart rate, and they had shown
      improvements in blood chemistry markers such as lipid profiles, insulin, and high
      sensitivity C-reactive protein. There was a significant reduction in both cfPWV
      and baPWV following the intervention when compared to baseline levels. Moreover,
      the AIx and aortic systolic blood pressure were significantly reduced after the
      intervention. The diet and exercise intervention significantly increased cardiac
      autonomic modulation (determined by improved SDNN, RMSSD, TP LF, HF, and LF/HF),
      which was partly due to changes in heart rate, insulin resistance, and the
      inflammatory pattern. Furthermore, we observed a correlation between enhanced
      cardiac autonomic modulation (LF/HF) and decreased arterial stiffness, as
      measured by central cfPWV and systemic baPWV. DISCUSSION: An 8-week combined
      intervention of diet and exercise is effective in improving cardiac autonomic
      function in obese adults, with an associated decrease in central and systemic
      arterial stiffness.

PMID- 29018629
TI  - In Vivo Brain Magnetic Resonance Spectroscopy: A Measurement of Biomarker
      Sensitivity to Post-Processing Algorithms.
AB  - Clinical translation of reported biomarkers requires reliable and consistent
      algorithms to derive biomarkers. However, the literature reports statistically
      significant differences between 1-D MRS measurements from control groups and
      subjects with disease states but frequently provides little information on the
      algorithms and parameters used to process the data. The sensitivity of in vivo
      brain magnetic resonance spectroscopy biomarkers is investigated with respect to
      parameter values for two key stages of post-acquisitional processing. Our effort
      is specifically motivated by the lack of consensus on approaches and parameter
      values for the two critical operations, water resonance removal, and baseline
      correction. The different stages of data processing also introduce varying levels
      of uncertainty and arbitrary selection of parameter values can significantly
      underutilize the intrinsic differences between two classes of signals. The
      sensitivity of biomarkers points to the need for a better understanding of how
      all stages of post-acquisitional processing affect biomarker discovery and
      ultimately, clinical translation. Our results also highlight the possibility of
      optimizing biomarker discovery by the careful selection of parameters that best
      reveal class differences. Using previously reported data and biomarkers, our
      results demonstrate that small changes in parameter values affect the statistical
      significance and corresponding effect size of biomarkers. Consequently, it is
      possible to increase the strength of biomarkers by selecting optimal parameter
      values in different spectral intervals. Our analyses with a previously reported
      data set demonstrate an increase in effect sizes for wavelet-based biomarkers of
      up to 36%, with increases in classification performance of up to 12%.

PMID- 29018630
TI  - A Versatile Ultrasound Simulation System for Education and Training in High
      Fidelity Emergency Scenarios.
AB  - Point of care ultrasonography and the related focused assessment with sonography
      for trauma protocol, if performed by experienced physicians, is a highly
      sensitive examination, and specific for the detection of free fluids. Different
      systems and methods have been proposed for training, including simulation as one
      of the most efficient. This paper presents an ultrasound training system,
      specifically designed to be used during bedside high fidelity simulation
      scenarios, that could facilitate the learning process. The development of the
      proposed system exploited novel rapid prototyping electronic boards as a means to
      obtain good performances with a low cost. Moreover, the design of the data
      structure permits the construction of a library that caters for individual needs,
      with the possibility of adding emergency scenarios, collecting pictures or
      videos, as well as 3-D volumes. The device has been compared with currently
      commercial ultrasound simulators and its innovative aspects have been
      highlighted. Finally, it has been tested during a training session in order to
      evaluate features, such as realism and user-friendliness.

PMID- 29018631
TI  - Multi-Parameter Ensemble Learning for Automated Vertebral Body Segmentation in
      Heterogeneously Acquired Clinical MR Images.
AB  - The development of quantitative imaging biomarkers in medicine requires automatic
      delineation of relevant anatomical structures using available imaging data.
      However, this task is complicated in clinical medicine due to the variation in
      scanning parameters and protocols, even within a single medical center. Existing
      literature on automatic image segmentation using MR data is based on the analysis
      of highly homogenous images obtained using a fixed set of pulse sequence
      parameters (TR/TE). Unfortunately, algorithms that operate on fixed scanning
      parameters do not avail themselves to real-world daily clinical use due to the
      existing variation in scanning parameters and protocols. Thus, it is necessary to
      develop algorithmic techniques that can address the challenge of MR image
      segmentation using real clinical data. Toward this goal, we developed a multi
      parametric ensemble learning technique to automatically detect and segment lumbar
      vertebral bodies using MR images of the spine. We use spine imaging data to
      illustrate our techniques since low back pain is an extremely common condition
      and a typical spine clinic evaluates patients that have been referred with a wide
      range of scanning parameters. This method was designed with special emphasis on
      robustness so that it can perform well despite the inherent variation in scanning
      protocols. Specifically, we show how a single multi-parameter ensemble model
      trained with manually labeled T2 scans can autonomously segment vertebral bodies
      on scans with echo times varying between 24 and 147 ms and relaxation times
      varying between 1500 and 7810 ms. Furthermore, even though the model was trained
      using T2-MR imaging data, it can accurately segment vertebral bodies on T1-MR and
      CT, further demonstrating the robustness and versatility of our methodology. We
      believe that robust segmentation techniques, such as the one presented here, are
      necessary for translating computer assisted diagnosis into everyday clinical
      practice.

PMID- 29018632
TI  - Patient-Specific Oscillometric Blood Pressure Measurement: Validation for
      Accuracy and Repeatability.
AB  - Oscillometric devices are widely used for automatic cuff blood pressure (BP)
      measurement. These devices estimate BP from the oscillometric cuff pressure
      waveform using population average methods. Hence, the devices may only be
      accurate over a limited BP range. The objective was to evaluate a new patient
      specific method, which estimates BP by fitting a physiologic model to the same
      waveform. One-hundred and forty-five cardiac catheterization patients and normal
      adults were included for study. The oscillometric cuff pressure waveform was
      obtained with an office device, while reference BP was measured via brachial
      artery catheterization or auscultation, during baseline and/or nitroglycerin
      administration. Fifty-seven of the subject records were utilized for refining the
      patient-specific method, while the remaining 88 subject records were employed for
      evaluation. The precision errors for all BP levels of the patient-specific method
      ranged from 6.3 to 7.6 mmHg. These errors were significantly lower than those of
      the office device (by 29% on average) in subjects with high pulse pressure (>50
      mmHg) while being comparable to those of the device in subjects with normal pulse
      pressure (<50 mmHg). The bias and precision of the differences in repeated
      estimates for all BP levels of the patient-specific method ranged from 0.1 to 1.1
      and 2.1 to 5.9 mmHg, respectively. These precision differences were significantly
      lower than those of the office device (by 64% on average). The patient-specific
      method may afford more accurate automatic cuff BP measurement in patients with
      large artery stiffening while limiting the number of required cuff
      inflations/deflations per measurement.

PMID- 29018633
TI  - A Software Tool for Heart AVJ Motion Tracking Using Cine Cardiovascular Magnetic
      Resonance Images.
AB  - One important index to assess left ventricular diastolic function is the
      quantitative measurement of atrioventricular junction (AVJ) motion in one cardiac
      cycle including systole and diastole. The best way to perform the measurement is
      to use a software tool that can conduct AVJ motion tracking from cine
      cardiovascular magnetic resonance (CMR) images. In this paper, a software tool
      for this purpose is presented by using the insight segmentation and registration
      toolkit (ITK), the visualization toolkit (VTK), and Qt. We propose a surface area
      based tracking approach in the software tool. In the tracking approach to obtain
      the surface area swept by six points being tracked, we manually select six points
      from four-, three- and two-chamber views of CMR images. After that, we
      reconstruct the 3-D coordinates of the six points from image acquisition
      parameters extracted from DICOM files. We perform interpolation by using
      parametric cubic curve fitting techniques. From the curve fitting results, we
      finally obtain the surface areas for all time points in one cardiac cycle. The
      software tool has been successfully implemented. The functionality include single
      point-based tracking, surface area-based tracking by using 6 tracked points,
      generation of displacement, sweep surface area and velocity, and generation of
      tracking movies. From the software engineering practice, it is concluded that
      ITK, VTK, and Qt are very handy software systems to implement automatic image
      analysis functions for CMR images, such as quantitative measure of motion by
      visual tracking. The software tool provides a convenient and efficient way to
      measure AVJ motion and extends the scope of methods for ventricular function
      assessment.

PMID- 29018634
TI  - Detection of Paroxysms in Long-Term, Single-Channel EEG-Monitoring of Patients
      with Typical Absence Seizures.
AB  - Absence seizures are associated with generalized 2.5-5 Hz spike-wave discharges
      in the electroencephalogram (EEG). Rarely are patients, parents, or physicians
      aware of the duration or incidence of seizures. Six patients were monitored with
      a portable EEG-device over four times 24 h to evaluate how easily outpatients are
      monitored and how well an automatic seizure detection algorithm can identify the
      absences. Based on patient-specific modeling, we achieved a sensitivity of 98.4%
      with only 0.23 false detections per hour. This yields a clinically satisfying
      performance with a positive predictive value of 87.1%. Portable EEG-recorders
      identifying paroxystic events in epilepsy outpatients are a promising tool for
      patients and physicians dealing with absence epilepsy. Albeit the small size of
      the EEG-device, some children still complained about the obtrusive nature of the
      device. We aim at developing less obtrusive though still very efficient devices,
      e.g., hidden in the ear canal or below the skin.

PMID- 29018635
TI  - A New Wavelet-Based ECG Delineator for the Evaluation of the Ventricular
      Innervation.
AB  - T-wave amplitude (TWA) has been proposed as a marker of the innervation of the
      myocardium. Until now, TWA has been calculated manually or with poor algorithms,
      thus making its use not efficient in a clinical environment. We introduce a new
      wavelet-based algorithm for the delineation QRS complexes and T-waves, and the
      automatic calculation of TWA. When validated in the MIT/BIH Arrhythmia database,
      the QRS detector achieved sensitivity and positive predictive value of 99.84% and
      99.87%, respectively. The algorithm was validated also on the QT database and it
      achieved sensitivity of 99.50% for T-peak detection. In addition, the algorithm
      achieved delineation accuracy that is similar to the differences in delineation
      between expert cardiologists. We applied the algorithm for the evaluation of the
      influence in TWA of anticholinergic and antiadrenergic drugs (i.e., atropine and
      metoprolol) for healthy subjects. We found that the TWA decreased significantly
      with atropine and that metoprolol caused a significant increase in TWA, thus
      confirming the clinical hypothesis that the TWA is a marker of the innervation of
      the myocardium. The results of this paper show that the proposed algorithm can be
      used as a useful and efficient tool in clinical practice for the automatic
      calculation of TWA and its interpretation as a non-invasive marker of the
      autonomic ventricular innervation.

PMID- 29018636
TI  - Detecting Dementia Through Interactive Computer Avatars.
AB  - This paper proposes a new approach to automatically detect dementia. Even though
      some works have detected dementia from speech and language attributes, most have
      applied detection using picture descriptions, narratives, and cognitive tasks. In
      this paper, we propose a new computer avatar with spoken dialog functionalities
      that produces spoken queries based on the mini-mental state examination, the
      Wechsler memory scale-revised, and other related neuropsychological questions. We
      recorded the interactive data of spoken dialogues from 29 participants (14
      dementia and 15 healthy controls) and extracted various audiovisual features. We
      tried to predict dementia using audiovisual features and two machine learning
      algorithms (support vector machines and logistic regression). Here, we show that
      the support vector machines outperformed logistic regression, and by using the
      extracted features they classified the participants into two groups with 0.93
      detection performance, as measured by the areas under the receiver operating
      characteristic curve. We also newly identified some contributing features, e.g.,
      gap before speaking, the variations of fundamental frequency, voice quality, and
      the ratio of smiling. We concluded that our system has the potential to detect
      dementia through spoken dialog systems and that the system can assist health care
      workers. In addition, these findings could help medical personnel detect signs of
      dementia.

PMID- 29018637
TI  - Tissue Variability and Antennas for Power Transfer to Wireless Implantable
      Medical Devices.
AB  - The design of effective transcutaneous systems demands the consideration of
      inevitable variations in tissue characteristics, which vary across body areas,
      among individuals, and over time. The purpose of this paper was to design and
      evaluate several printed antenna topologies for ultrahigh frequency (UHF)
      transcutaneous power transfer to implantable medical devices, and to investigate
      the effects of variations in tissue properties on dipole and loop topologies.
      Here, we show that a loop antenna topology provides the greatest achievable gain
      with the smallest implanted antenna, while a dipole system provides higher
      impedance for conjugate matching and the ability to increase gain with a larger
      external antenna. In comparison to the dipole system, the loop system exhibits
      greater sensitivity to changes in tissue structure and properties in terms of
      power gain, but provides higher gain when the separation is on the order of the
      smaller antenna dimension. The dipole system was shown to provide higher gain
      than the loop system at greater implant depths for the same implanted antenna
      area, and was less sensitive to variations in tissue properties and structure in
      terms of power gain at all investigated implant depths. The results show the
      potential of easily-fabricated, low-cost printed antenna topologies for UHF
      transcutaneous power, and the importance of environmental considerations in
      choosing the antenna topology.

PMID- 29018638
TI  - Automatic Sleep Monitoring Using Ear-EEG.
AB  - The monitoring of sleep patterns without patient's inconvenience or involvement
      of a medical specialist is a clinical question of significant importance. To this
      end, we propose an automatic sleep stage monitoring system based on an
      affordable, unobtrusive, discreet, and long-term wearable in-ear sensor for
      recording the electroencephalogram (ear-EEG). The selected features for sleep
      pattern classification from a single ear-EEG channel include the spectral edge
      frequency and multi-scale fuzzy entropy, a structural complexity feature. In this
      preliminary study, the manually scored hypnograms from simultaneous scalp-EEG and
      ear-EEG recordings of four subjects are used as labels for two analysis
      scenarios: 1) classification of ear-EEG hypnogram labels from ear-EEG recordings;
      and 2) prediction of scalp-EEG hypnogram labels from ear-EEG recordings. We
      consider both 2-class and 4-class sleep scoring, with the achieved accuracies
      ranging from 78.5% to 95.2% for ear-EEG labels predicted from ear-EEG, and 76.8%
      to 91.8% for scalp-EEG labels predicted from ear-EEG. The corresponding Kappa
      coefficients range from 0.64 to 0.83 for Scenario 1, and indicate substantial to
      almost perfect agreement, while for Scenario 2 the range of 0.65-0.80 indicates
      substantial agreement, thus further supporting the feasibility of in-ear sensing
      for sleep monitoring in the community.

PMID- 29018639
TI  - Managing Heart Failure at Home With Point-of-Care Diagnostics.
AB  - The objective of this paper is development of an inexpensive point-of-care sensor
      for detecting the primary heart failure marker peptide, NT-proBNP. The device
      technology is based on an antibody sandwich assay, but with three innovative
      aspects. First, chemical amplification is carried out via oxidation of silver
      nanoparticles (NPs) attached to signaling antibodies rather than by enzymatic
      amplification. The electrochemical method is faster and eliminates the need for
      long-term storage of enzymes. Second, the antibody sandwich is formed on mobile
      magnetic beads. This enhances the rate of mass transfer of the biomarker and the
      signaling antibody to the primary detection antibody, which is immobilized on the
      magnetic beads. Third, the sensor itself is fabricated on a paper platform with
      screen-printed electrodes. This coupled with assembly by simple paper folding,
      keeps the cost of the sensor low. Here, we report on two separate assays. The
      first is based on a simple biotin-streptavidin conjugate, which is a preliminary
      model for the antibody assay. The results indicate a detection limit of 2.1 pM of
      silver NPs and an assay time of 7 min. The actual NT-proBNP antibody assay takes
      somewhat longer, and the dynamic detection range is higher: 2.9-582 nM. On the
      basis of the results presented in this paper, we conclude that this inexpensive
      paper-based sensor represents a viable technology for point-of-care testing of NT
      proBNP, but nevertheless several challenges remain prior to clinical
      implementation. These include attaining a lower detection limit and better
      reproducibility, and optimizing the device for human blood.

PMID- 29018640
TI  - A Multi-Classifier System for Automatic Mitosis Detection in Breast
      Histopathology Images Using Deep Belief Networks.
AB  - Mitotic count is an important diagnostic factor in breast cancer grading and
      prognosis. Detection of mitosis in breast histopathology images is very
      challenging mainly due to diffused intensities along object boundary and shape
      variation in different stages of mitosis. This paper demonstrates an accurate
      technique for detecting the mitotic cells in Hematoxyline and Eosin stained
      images by step by step refinement of segmentation and classification stages.
      Krill Herd Algorithm-based localized active contour model precisely segments cell
      nuclei from background stroma. A deep belief network based multi-classifier
      system classifies the labeled cells into mitotic and nonmitotic groups. The
      proposed method has been evaluated on MITOS data set provided for MITOS-ATYPIA
      contest 2014 and also on clinical images obtained from Regional Cancer Centre
      (RCC), Thiruvananthapuram, which is a pioneer institute specifically for cancer
      diagnosis and research in India. The algorithm provides improved performance
      compared with other state-of-the-art techniques with average F-score of 84.29%
      for the MITOS data set and 75% for the clinical data set from RCC.

PMID- 29018641
TI  - Prevalence and Determinants of Frozen Shoulder in Patients with Diabetes: A
      Single Center Experience from Pakistan.
AB  - Introduction Frozen shoulder (FS) or adhesive capsulitis is a constellation of
      symptoms like pain, stiffness, and/or functional deficit at the glenohumeral
      joint. It is one of the musculoskeletal complications in patients with diabetes
      that can be particularly debilitating. The aim of this study is to estimate the
      prevalence of FS and to compare the determinants of this disease in a population
      with diabetes from Lahore, Pakistan. Materials and Methods We carried out this
      cross-sectional study on a systematically randomized sample of 80 patients with
      diabetes. It included 38 males and 42 females from 2,964 patients registered at
      the Diabetes Management Center, Services Hospital Lahore, Pakistan. The study was
      conducted in the months of April, May, and June 2017. A structured questionnaire
      was designed and the responses of patients were recorded at the clinic after
      informed verbal and written consent. The questionnaire outlined the key factors
      that can lead to a higher frequency of FS in patients with diabetes. Results
      Thirty-three of the total 80 respondents included in the study were diagnosed
      with FS. The estimated prevalence of FS in diabetics from this data was 41.3% in
      Lahore, which is an urban area of Pakistan with a population of more than seven
      million. Female sex, insulin dependence, uncontrolled blood glucose levels, and a
      positive family history were associated with a significantly higher prevalence of
      FS. In our study, most patients with FS were in Stage 1 of the disease and had
      unilateral involvement. Conclusion The present study shows that the prevalence of
      FS is higher in patients with diabetes residing in Lahore than in comparable
      foreign populations with diabetes. It can be attributed to socioeconomic status,
      lack of awareness, a higher threshold for diagnosis, and/or poor glycemic
      control. Mass awareness campaigns, especially for female patients with diabetes,
      are required to be initiated to create awareness about the disease and to
      facilitate early diagnosis and appropriate management. In-depth and multicenter
      studies are needed to further explore the association between FS and diabetes.

PMID- 29018642
TI  - Pulmonary Embolism Secondary to Testosterone-Enhancing Herbal Supplement Use.
AB  - Decreased testosterone levels in men are often a normal sign of aging.
      Testosterone replacement therapy (TRT) is a well-established option for those
      with symptomatic hypogonadism related to low testosterone levels. Conversely,
      designer herbal supplements in the context of testosterone supplementation are
      poorly studied, yet remain popular among aging men who seek the well-known, often
      enhancing, effects of testosterone that involve muscle mass and sexual
      function/drive. In 2014, the Food and Drug Administration (FDA) issued a warning
      about the significant risk of venous clots secondary to testosterone product use.
      Testosterone-induced polycythemia is one of the proposed mechanisms for this
      increased clotting propensity. Increased thromboxane A2 receptor density on
      platelets and increased platelet aggregation have also been linked to
      testosterone treatment in men. Fenugreek extract is a common active ingredient in
      commercially available herbal supplements that are often marketed as testosterone
      enhancers. It is thought that certain fenugreek compounds inhibit aromatase and 5
      alpha-reductase activity, leading to diminished testosterone breakdown. However,
      the efficacy and safety profile of this agent in its use for boosting
      testosterone levels are unclear. In this case report, we present a patient with
      new-onset, bilateral pulmonary embolism possibly associated with the daily use of
      fenugreek-containing testosterone supplements.

PMID- 29018643
TI  - Case Reports, Case Series - From Clinical Practice to Evidence-Based Medicine in
      Graduate Medical Education.
AB  - Case reports and case series or case study research are descriptive studies that
      are prepared for illustrating novel, unusual, or atypical features identified in
      patients in medical practice, and they potentially generate new research
      questions. They are empirical inquiries or investigations of a patient or a group
      of patients in a natural, real-world clinical setting. Case study research is a
      method that focuses on the contextual analysis of a number of events or
      conditions and their relationships. There is disagreement among physicians on the
      value of case studies in the medical literature, particularly for educators
      focused on teaching evidence-based medicine (EBM) for student learners in
      graduate medical education. Despite their limitations, case study research is a
      beneficial tool and learning experience in graduate medical education and among
      novice researchers. The preparation and presentation of case studies can help
      students and graduate medical education programs evaluate and apply the six
      American College of Graduate Medical Education (ACGME) competencies in the areas
      of medical knowledge, patient care, practice-based learning, professionalism,
      systems-based practice, and communication. A goal in graduate medical education
      should be to assist residents to expand their critical thinking, problem-solving,
      and decision-making skills. These attributes are required in the teaching and
      practice of EBM. In this aspect, case studies provide a platform for developing
      clinical skills and problem-based learning methods. Hence, graduate medical
      education programs should encourage, assist, and support residents in the
      publication of clinical case studies; and clinical teachers should encourage
      graduate students to publish case reports during their graduate medical
      education.

PMID- 29018644
TI  - Mycobacterium Genavense Granuloma Mimicking a Brain Tumor: A Case Report.
AB  - Mycobacterium genavense (M. genavense) is a rare, non-tuberculous organism that
      commonly leads to gastrointestinal infections in immunocompromised patients. Only
      two cases of intracranial M. genavense infection have been reported to date. We
      describe a third case of M. genavense granuloma mimicking a right parietal
      intracranial mass, and review the literature on this exceedingly rare pathology.

PMID- 29018646
TI  - Hernia of Morgagni in the Elderly: A Case Report.
AB  - Congenital diaphragmatic hernias are infrequently encountered in adult patients.
      A rare type of this hernia is the Morgagni's hernia. Although they remain
      asymptomatic in a majority of patients, we present the case of an elderly patient
      who presented to us with abdominal pain and upper gastrointestinal bleeding.

PMID- 29018645
TI  - Dietary Therapy for Von Gierke's Disease: A Case Report.
AB  - Von Gierke's disease, also known as glycogen storage disease (GSD) type 1A, is an
      autosomal recessive disease in which there is an inability to cleave glycogen to
      glucose because of a glucose 6 phosphate deficiency resulting in hypoglycemia and
      lactic acidosis. The patient may present with hepatomegaly and signs and symptoms
      of hypoglycemia. We diagnosed a case of Von Gierke's disease in a seven-month-old
      female infant who was admitted for abdominal distension, vomiting, and lethargy
      for a duration of four months with characteristic rounded doll's face, fatty
      cheeks, protuberant abdomen, and massive hepatomegaly. Lab investigations showed
      low hemoglobin, low blood sugar level, lactic acidosis, hyperlipidemia,
      hyperuricemia, mild elevation of liver enzymes, and high anion gap metabolic
      acidosis. The diagnosis was confirmed with a liver biopsy and dietary treatment
      was started. This case report highlights the value of dietary therapy in
      improving the quality of life and survival and minimizing complications.

PMID- 29018647
TI  - Burden of Arrhythmias in Epilepsy Patients: A Nationwide Inpatient Analysis of
      1.4 Million Hospitalizations in the United States.
AB  - Arrhythmias have been one of the common complications in epilepsy patients and
      have also been the reason for death. However, limited data exist about the burden
      and outcomes of arrhythmias by subtypes in epilepsy. Our study aims at evaluating
      the burden and differences in outcomes of various subtypes of arrhythmias in
      epilepsy patient population. The Nationwide Inpatient Sample (NIS) database from
      2014 was examined for epilepsy and arrhythmias related discharges using
      appropriate International Classification of Disease, Ninth Revision Clinical
      Modification (ICD-9-CM) codes. The frequency of arrhythmias, gender differences
      in arrhythmia by subtypes, in-hospital outcomes and mortality predictors was
      analyzed. A total of 1,424,320 weighted epilepsy patients was determined and
      included in this study. Around 23.9% (n =277,230) patients had cardiac
      arrhythmias. The most frequent arrhythmias in the descending frequency were:
      atrial fibrillation (AFib) 9.7%, other unspecified causes 7.3%, sudden cardiac
      arrest (SCA) 1.4%, bundle branch block (BBB) 1.2%, ventricular tachycardia (VT)
      1%. Males were more predisposed to cardiac arrhythmias compared to females (OR
      [odds ratio]: 1.1, p <0.001). The prevalence of most subtypes arrhythmias was
      higher in males. Arrhythmias were present in nearly a quarter of patients with
      epilepsy. Life threatening arrhythmias were more common in male patients. The
      length of stay (LOS) and mortality were significantly higher in epilepsy patients
      with arrhythmia. It is imperative to develop early diagnosis and prompt
      therapeutic measures to reduce this burden and poor outcomes due to concomitant
      arrhythmias in epilepsy patients.

PMID- 29018648
TI  - Os Odontoideum: A Comprehensive Clinical and Surgical Review.
AB  - Os odontoideum (OO) is a rare anomaly of the odontoid process first described by
      Giacomini in 1886. There is considerable debate about the origin of this anomaly,
      whether congenital or acquired, though a growing body of evidence favors the
      latter. Using PubMed, we reviewed the literature on OO with regards to its
      etiology, clinical presentations, diagnostic modalities, and management.
      Manuscripts cited in reviews were also searched manually. Because the medical
      literature on this condition is limited, our understanding of the natural history
      and management of OO is still vague. The management guidelines for asymptomatic
      OO are preliminary. Therefore, we need more large-center studies to investigate
      this condition further.

PMID- 29018649
TI  - Rapid Recanalization Using TrevoProVue through a 4.2 Fr Catheter without a
      Guiding Catheter via Transbrachial Approach: A Case Report.
AB  - Mechanical thrombectomy with a stent retriever has been reported to achieve high
      rates of successful recanalization, and reduce disability and mortality in
      patients with acute ischemic stroke (AIS) due to proximal vessel occlusion.
      However, in a few cases, the treatment is difficult due to artery tortuosity or
      other factors. The authors present a case of a 94-year-old man presenting with
      acute right middle cerebral artery occlusion. We attempted to treat using a stent
      retriever via transfemoral approach, but failed to advance the guiding catheter
      into the right internal carotid artery due to femoral artery tortuosity and a
      type III arch. By changing approaches from transfemoral to transbrachial and by
      using TrevoProVue through a 4.2 Fr Simmons-type catheter without a guiding
      catheter, we were able to achieve rapid recanalization in only 26 minutes from
      brachial artery puncture to reperfusion. In conclusion, rapid reperfusion in an
      AIS patient was successfully achieved by combining a stent retriever with a 4.2
      Fr catheter (without a guiding catheter) and a transbrachial approach (as opposed
      to a transfemoral approach). When the transfemoral approach is not feasible, we
      recommend consideration of this strategy as an alternative.

PMID- 29018650
TI  - Surgical Treatment of Rotational Vertebral Artery Syndrome Induced by Spinal
      Tumor: A Case Report and Literature Review.
AB  - Vertebrobasilar insufficiency (VBI) provoked by physiological head rotation is
      known as rotational vertebral artery syndrome (RVAS) or Bow Hunter syndrome. RVAS
      most often occurs at C1-2 level with head rotation and presents with symptoms of
      VBI. Several previously published studies have reported RVAS at subaxial sites
      (V2 segment), however, tumor-induced RVAS has never been reported. The authors
      report the first case of RVAS at V2 segment due to compression from a spinal
      tumor. A 71-year-old man presented with symptoms of dizziness provoked by head
      rotation or neck extension. computed tomography (CT) angiography and dynamic
      cerebral angiography revealed circumferential stenosis with neutral neck position
      and complete occlusion of the left dominant vertebral artery (VA) at C5 level
      with his neck extended or rotated to the left. Complete neurological recovery was
      achieved after removal of a spinal osteochondroma and surgical decompression of
      the left VA via an anterior approach. Spinal tumors should be included in the
      differential diagnosis in cases of RVAS. Spinal degenerations or sarcomatous
      transformation of the tumor could lead to clinical manifestations of RVAS in
      cases with spinal osteochondroma. Complete removal of the tumor with or without
      spinal fusion would be the treatment of choice, in addition to medical treatment
      in the cases of acute stroke.

PMID- 29018651
TI  - A Case of Vertebral Artery Fusiform Aneurysm Treated by Flow Alteration:
      Successful Prediction of Therapeutic Effects Using Computational Fluid Dynamics.
AB  - The treatment of intracranial complicated aneurysms remains challenging. In
      patients with complicated aneurysms that are neither clippable nor coilable, flow
      alteration treatment (FAT) with a combined procedure of proximal/distal occlusion
      or trapping of an aneurysm with bypass surgery has been reported. However, it is
      difficult to predict whatever FAT can achieve aneurysmal obliteration without
      ischemic complications. A 69-year-old female was incidentally diagnosed with a
      left vertebral artery (VA) fusiform aneurysm distal to the left posterior
      inferior cerebellar artery (PICA). Because one-year follow-up three-dimensional
      computed tomography angiography showed that the aneurysm grew significantly,
      surgical management was considered the therapy of choice. For determining
      treatment strategies, we assumed left VA occlusion at the proximal to the left
      PICA as a FAT model and performed computational fluid dynamics (CFD) analyses.
      The FAT model had much lower wall shear stress and shear rate at the aneurysm
      dome than presumed thresholds necessary to thrombus formation, while those at the
      PICA were obviously higher than the thresholds, and streamlines into the left
      PICA from the distal VA were preserved. These findings theoretically meant that
      surgical occlusion of the left VA proximal to the left PICA and aneurysm would
      induce intra-aneurysmal thrombus formation with preservation of the left PICA
      flow. The treatment was performed successfully and achieved the predicted
      results. CFD simulations may be useful to predict effects of FAT for complicated
      aneurysms.

PMID- 29018652
TI  - Anastomotic Aneurysm Formation after High Flow Bypass Surgery: A Case Report with
      Histopathological Study.
AB  - Bypass surgery is often used in the treatment of large and giant aneurysms. Major
      complications that often arise during the perioperative period include cranial
      nerve palsy, ischemic complications, and hyperperfusion. However, there have been
      a few reports about late onset complications such as anastomotic aneurysms. In
      particular, anastomotic aneurysm after high flow bypasses has never been
      reported. A 57-year-old woman who had been suffering from left eye pain was
      diagnosed with a large aneurysm of the left internal carotid artery (ICA) in the
      cavernous portion. She was treated with high flow bypass surgery using radial
      artery graft and proximal ICA ligation. One and a half year after surgery, a de
      novo aneurysm (7.5 mm in maximum diameter) was detected in the anastomotic site.
      To prevent rupture, the aneurysm was resected and the middle cerebral artery
      (MCA) was reconstructed via superficial temporal artery (STA)-MCA bypass.
      Postoperative course was uneventful and the anastomotic aneurysm did not recur
      until 2 years after second surgery. Histological evaluation of the anastomotic
      aneurysm demonstrated loss of smooth muscle cells and proliferation of neointima,
      features consistent with a true aneurysm. Interestingly, the above changes were
      prominent in the radial artery graft while the MCA was almost histologically
      intact. As such, intraoperative intimal damage and postoperative hemodynamic
      stress to the radial artery graft may be a cause of aneurysm formation.
      Anastomotic aneurysm may occur after high flow bypass, necessitating careful
      postoperative follow-up.

PMID- 29018653
TI  - Chiari Type 1 Malformation-induced Intracranial Hypertension with Diffuse Brain
      Edema Treated with Foramen Magnum Decompression: A Case Report.
AB  - Chiari type 1 malformation (CM1) rarely causes papilloedema, which is indicative
      of high intracranial pressure with or without ventricular dilatation.
      Furthermore, concomitant brain parenchymal abnormalities have not been reported
      to date. In this paper, the authors report on a young woman of CM1-induced
      intracranial hypertension (ICH) with diffuse brain edema with a focus on venous
      sinus assessment, and discuss the surgical strategy. A 24-year-old woman
      presented to Nagoya University Hospital complaining of 4-year history of severe
      occipital headache and blurry vision with slowly progressive worsening. Head and
      whole spine MRI showed a CM1 with diffuse white matter hyperintensities (WMH) on
      T2-weighted imaging and narrowed brain sulci without hydrocephalus. Lumbar
      puncture revealed extremely high opening pressure. Detailed blood examination and
      other radiographical imaging studies denied the presence of tumor, collagen
      disease, encephalitis and other entities. Head magnetic resonance venography and
      angiography demonstrated severe transverse sinus stenosis on both sides. Foramen
      magnum decompression was performed to alleviate the ICH by restoration of
      cerebrospinal fluid (CSF) stagnation at the foramen magnum with successful
      outcome. The patient completely recovered from preoperative symptoms immediately
      after surgery. The diffuse WMH and narrowing brain sulci have been resolving. The
      most feasible explanation for this complicated pathophysiology was ICH induced by
      CM1 led to transverse sinus collapse, resulting in diffuse WMH as a result of
      venous hypertension. This case report is the first illustration of successful
      surgical treatment of CM1 with diffuse brain edema with a focus on venous sinus
      assessment.

PMID- 29018654
TI  - Double Crush of L5 Spinal Nerve Root due to L4/5 Lateral Recess Stenosis and Bony
      Spur Formation of Lumbosacral Transitional Vertebra Pseudoarticulation: A Case
      Report and Review.
AB  - We present a case of double-crushed L5 nerve root symptoms caused by inside and
      outside of the spinal canal with spur formation of the lumbosacral transitional
      vertebra (LSTV). A 78-year-old man presented with 7-year history of moderate
      paresis of his toe and left leg pain when walking. Magnetic resonance imaging
      (MRI) revealed spinal stenosis at the L3/4 and 4/5 spinal levels and he underwent
      wide fenestration of both levels. Leg pain disappeared and 6-min walk distance
      (6MWD) improved after surgery, however, the numbness in his toes increased and
      6MWD decreased 9 months after surgery. Repeated MR and 3D multiplanar
      reconstructed computed tomography (CT) images showed extraforaminal impingement
      of the L5 root by bony spur of the left LSTV. He underwent second decompression
      surgery of the L5/S via the left sided Wiltse approach, resulting in the
      improvement of his symptoms. The impingement of L5 spinal nerve root between the
      transverse process of the fifth lumbar vertebra and the sacral ala is a rare
      entity of the pathology called "far-out syndrome (FOS)". Especially, the bony
      spur formation secondary to the anomalous articulation of the LSTV (LSPA) has not
      been reported. These articulations could be due to severe disc degeneration,
      following closer distance and contact between the transverse process and the
      sacral ala. To our knowledge, this is the first report describing a case with
      this pathology and may be considered in cases of failed back surgery syndromes
      (FBSS) of the L5 root symptoms.

PMID- 29018655
TI  - The Involvement of Sensory-motor Networks in Reflex Seizure.
AB  - Reflex seizures are epileptic events triggered by specific external stimuli, or
      less commonly, internal mental stimuli. Understanding the characteristics of
      reflex seizures is important to elucidate the mechanisms underlying network
      abnormalities in epileptic conditions. This report details a patient with
      medically intractable reflex seizures provoked by sensory stimuli to the
      patient's right foot. Single-photon emission computed tomography (SPECT) during
      the seizure induced by sensory stimulation showed hyperperfusion in broad sensory
      motor networks (dorsal column-medial lemniscus pathway, left thalamus, bilateral
      postcentral gyri and posterior parietal cortices, left supplementary motor area
      (SMA), and left paracentral lobule) and left caudateputamen. The irritative zones
      and ictal onset zone were localized to the left medial frontoparietal (SMA,
      anterior and middle cingulate gyrus, and paracentral lobule) and lateral
      posterior parietal cortices, as evidenced by amelioration of reflex seizures
      following intracranial electroencephalography and surgical resection of these
      areas. The neuroradiological and electrophysiological findings in our case study
      illustrate that the mechanism of reflex seizures may be associated with
      hyperexcitability of the broad sensory-motor networks, including the basal
      ganglia. Disconnection of these networks is necessary to treat reflex seizures.

PMID- 29018656
TI  - How to manage traumatic optic neuropathy?

PMID- 29018658
TI  - Neuroimaging and clinical features of patients with optic nerve hypoplasia in
      Taiwan.
AB  - PURPOSE: To investigate the clinical and neuroradiographic features of Chinese
      patients with optic nerve hypoplasia (ONH). METHODS: This was a retrospective
      case series study. The medical records and magnetic resonance imaging (MRI)
      studies of patients diagnosed with ONH from September 2001 to December 2013 in
      the neuro-ophthalmology clinic of Taipei Veterans General Hospital were reviewed.
      RESULTS: A total of eight eyes of five patients with ONH were enrolled in this
      study (1 male, 4 females). The mean age at diagnosis was 14.5 +/- 12.0 years
      (range 0.25-30 years). Ocular examination revealed approximately half of the eyes
      had tortuous retinal vessels. In MRI studies, all patients had midline brain
      abnormalities including ectopic posterior pituitary gland (60%), agenesis of
      septum pellucidum (20%), and Rathke's cleft cyst (20%). Two patients had
      endocrinopathies-one suffered from hypopituitarism and the other had
      hyperprolactinemia. Both of them showed ocular findings of tortuous retinal
      vessels. CONCLUSION: A high prevalence of midline brain abnormalities was noted
      in ONH patients of Chinese ethnicity. The presence of tortuous retinal vessels in
      patients with a midline brain anomaly may indicate the occurrence of
      endocrinopathy.

PMID- 29018657
TI  - Major challenges in vitreoretinal surgery.
AB  - Since the first vitrectomy surgery was used for treatment of vitreoretinal
      diseases, surgical techniques and instrumentation have been rapidly improved in
      the past decades. However, there are complicated vitreoretinal diseases that
      cannot be successfully treated, even with state-of-the-art surgeries. The
      outcomes of some complicated cases are still poor due to different reasons and
      debates still remain in some areas regarding what are the best treatments. There
      is still a lack of full understanding on many complicated vitreoretinal diseases,
      such as the molecular basis of proliferative vitreoretinopathy (PVR), the role of
      scleral buckling (SB) in the management of rhegmatogenous retinal detachment
      (RRD), the optimal surgical consideration for pediatric RD, and the possibility
      of surgical management for various retinal degenerations and congenital retinal
      anomalies. This review discusses the current understandings of some complicated
      vitreoretinal diseases.

PMID- 29018659
TI  - Experience of scleritis and episcleritis at a tertiary center in Southern Taiwan.
AB  - PURPOSE: The purpose of this study was to review the clinical experiences of
      scleritis and episcleritis in Southern Taiwanese people during a 7-year period.
      METHODS: The charts of 89 patients (representing 101 eyes) who had visited our
      clinic from January 2003 to July 2010 were retrospectively reviewed. They were
      diagnosed as having episcleritis or scleritis. The medical charts, slit lamp
      photographs, and laboratory data were reviewed. Age, gender, laterality, previous
      surgery history, systemic diseases, follow-up duration, and ocular complications
      were collected. The patients were classified as having clinically suspected
      noninfectious scleritis (CSNIS), clinically suspected infectious scleritis
      (CSIS), and episcleritis for analysis. RESULTS: In the series of 89 patients
      (i.e., 101 eyes), 31 (34.8%; 32 eyes) patients had scleritis and 58 (65.2%; 69
      eyes) patients had episcleritis. Episcleritis and scleritis occurred slightly
      more frequently in women than in men. In the 31 patients (32 eyes) diagnosed with
      scleritis, 12 (38.7%) patients had CSIS and 19 (61.3%) patients had CSNIS.
      Patients with scleritis were older than patients with episcleritis (p < 0.001).
      Previous pterygium excision was associated with CSIS and necrotizing scleritis.
      CONCLUSION: Scleritis occurred in a more elderly population. It was more
      frequently associated with ocular complications, compared to episcleritis. Both
      CSNIS and CSIS were associated with a history of pterygium excisional surgery.
      Our series of patients had a high occurrence of necrotizing scleritis. All cases
      of necrotizing scleritis were associated with a history of previous ocular
      surgery.

PMID- 29018660
TI  - A lack of ongoing diabetes is an important factor in preserving eyes from late or
      suboptimally treated endogenous endophthalmitis secondary to Klebsiella
      pneumoniae liver abscess.
AB  - PURPOSE: The purpose of this study is to identify the possible factors for
      preserving the eyes after late or suboptimally treated endogenous endophthalmitis
      secondary to Klebsiella pneumoniae (KP) liver abscess. METHODS: A retrospective
      chart review was conducted for patients admitted with KP liver abscess from
      January 1991 to June 2012. RESULTS: Six hundred and ninety-three patients with KP
      liver abscess were recorded, in which endophthalmitis was identified in 53 cases
      (65 eyes, 8.29%). Diabetes was significantly associated with the development of
      endophthalmitis (p = 0.014). Eleven eyes received their last ocular treatment
      >=10 days and final vision >= counting fingers, and were defined as benign type
      KP endophthalmitis. The absence of diabetes was the only consistent candidate
      factor for benign type KP endophthalmitis. CONCLUSION: A lack of ongoing diabetes
      is an important factor in preserving eyes with late or suboptimally treated
      endogenous endophthalmitis second to KP liver abscess.

PMID- 29018661
TI  - Comparison of surgical outcomes after phacotrabeculectomy in primary angle
      closure glaucoma versus primary open-angle glaucoma.
AB  - PURPOSE: To compare postoperative outcomes and assess factors associated with
      intraocular pressure (IOP) reduction after phacotrabeculectomy in patients with
      primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG).
      METHODS: This is a retrospective study of patients who underwent
      phacotrabeculectomy between 2010 and 2013. Factors including age, gender, visual
      field (VF), the number of glaucoma medications used, biometric changes, IOP, and
      surgical success rates were compared between groups. RESULTS: There were 27 PACG
      and 34 POAG patients. The PACG group had a greater mean IOP reduction after
      phacotrabeculectomy compared to the POAG group (5.5 +/- 7.9 mmHg versus 2.0 +/-
      4.2 mmHg; p = 0.03). However, the final mean IOP was similar between the two
      groups (PACG: 12.2 +/- 4.8 mmHg, POAG: 12.3 +/- 3.1 mmHg; p = 0.92).
      Phacotrabeculectomy resulted in a mean decrease in axial length (AL) of 0.16 +/-
      0.15 mm in PACG and 0.16 +/- 0.11 mm in POAG (p = 0.96), and an increase in
      anterior chamber depth (ACD) of 1.41 +/- 0.91 mm in PACG, and 0.87 +/- 0.86 mm in
      POAG (p = 0.04). At 2 years follow-up, the cumulative success rate of
      phacotrabeculectomy was 74% in PACG and 62% in POAG. Multivariate analysis found
      that early glaucoma stage, greater postoperative increase in ACD, and high
      preoperative IOP were factors associated with greater IOP reduction. CONCLUSION:
      Postoperative success rates and mean IOP on the final visit after
      phacotrabeculectomy were similar between the PACG and POAG groups. Factors
      associated with IOP reduction were greater postoperative increase in ACD, and
      high preoperative IOP.

PMID- 29018662
TI  - Spectral-domain optical coherence tomography findings of subinternal limiting
      membrane hemorrhage in the macula before and after Nd:YAG laser treatment.
AB  - We reported the spectral-domain optical coherence tomography (SD-OCT) findings of
      a subinternal limiting membrane hemorrhage in the macula in one patient with
      Valsalva retinopathy and in one patient with macroaneurysm before and after
      neodymium-doped yttrium aluminum garnet (Nd:YAG) laser membranotomy. Within 1
      week, the Nd:YAG laser treatment facilitated rapid absorption of the hemorrhage
      in both patients. Spectral-domain optical coherence tomography was helpful before
      laser treatment to evaluate the exact location of the blood and after laser
      treatment to confirm the amount and location of residual hemorrhage, which was
      hard to confirm by only indirect ophthalmoscopy.

PMID- 29018663
TI  - Severe ocular complications following facial calcium hydroxylapatite injections:
      Two case reports.
AB  - Dermal soft-tissue augmentation using a filler is a technique widely used for
      facial cosmetic enhancement. However, potential complications following facial
      cosmetic injections have heightened the possibility of iatrogenic visual loss. We
      report two cases of severe ocular complications after nasal cosmetic enhancement.
      Both cases had poor visual outcomes in spite of emergency management. The second
      patient is a rare case with bilateral anterior ischemic optic neuropathy after
      dermal soft-tissue augmentation. The visual outcome was correlated with the
      location and the extent of the arterial embolization. Unfortunately, there is
      still no standard treatment protocol for vision-threatening complications.
      Clinicians should always keep in mind that embolic arterial occlusion may occur
      after augmentation.

PMID- 29018666
TI  - Glaucomatocyclitic crisis and glaucomatous optic neuropathy.

PMID- 29018664
TI  - Bilateral optic neuritis related to chronic inflammatory demyelinating
      polyneuropathy.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is a condition that
      mainly affects the peripheral nervous system; however, the central nervous system
      has also been involved in rare cases. Herein, we describe the case of a 33-year
      old man with CIDP who presented with progressively blurred vision and pain with
      eye movement in both eyes for 1 month. Ocular examination revealed reduced visual
      acuities of 0.15 (oculus unitas or OU) and unremarkable fundi (OU). Furthermore,
      bitemporal visual field defects and prolonged visually evoked potentials were
      evident. Brain magnetic resonance imaging revealed nothing remarkable along the
      optic nerve and chiasm. These findings were compatible with the diagnosis of
      bilateral optic neuritis. The patient's symptoms and visual acuity improved after
      5 days of intravenous (IV) corticosteroid pulse therapy, which was subsequently
      replaced by oral prednisolone therapy with a tapering schedule. The patient's
      visual acuity returned to 1.0 (OU) 6 months after treatment. However, bilateral
      optic neuritis recurred in 7 months while the patient was on oral prednisolone
      and azathioprine. IV corticosteroid pulse therapy was subsequently reinitiated
      and the patient's visual acuity returned gradually to 1.0 (OU). Bilateral optic
      neuritis is a rare manifestation of CIDP. It responded well to IV corticosteroid
      therapy in our case.

PMID- 29018665
TI  - Management of hypotony after glaucoma filtering surgery.
AB  - A 39-year-old male with open angle glaucoma in both eyes visited our clinic. The
      intraocular pressure (IOP) of both eyes fluctuated between 15 mmHg and 25 mmHg.
      The best corrected visual acuity (BCVA) was 20/20 in the right eye and 20/100 in
      the left eye. He underwent trabeculectomy with an adjunctive agent (mitomycin C;
      concentration, 0.2 mg/mL) smoothly on the right eye. After the removal of
      releasable sutures, the filtering bleb was prominent over the superior limbus for
      3 consecutive clock hours with an IOP of about 4-5 mmHg. The Seidel test result
      was negative, and the anterior chamber depth was moderate to deep. The BCVA of
      the right eye decreased to 20/100, and optical coherence tomography revealed
      macular edema. We injected sodium hyaluronate (Healon, Abbott Medical Optics,
      Santa Ana, CA, USA) into the anterior chamber 2 months after the operation, and
      repeated the same procedure 4 days later. After each injection, the IOP spiked up
      to 50 mmHg, and an intravenous infusion of mannitol was required. Sodium
      hyaluronate was found migrating into the bleb on post-injection day 1. Then we
      decided to revise the bleb by suturing the scleral flap at two sides. The IOP of
      the right eye returned to 10 mmHg 4 days after the revision surgery. The BCVA of
      the right eye recovered to 20/20 6 months after the revision. Optical coherence
      tomography also showed recovery from macular edema. One IOP-lowering agent (1%
      brinzolamide ophthalmic suspension) was required for IOP control after bleb
      revision. Early revision of the scleral flap may resolve hypotony and associated
      serious complications.

PMID- 29018667
TI  - Detecting optic nerve head deformation and retinal nerve fiber layer thinning in
      glaucoma progression.
AB  - The application of digital imaging technologies including confocal scanning laser
      ophthalmoscopy (CSLO), optical coherence tomography (OCT), and scanning laser
      polarimetry (SLP) has significantly improved the detection of optic nerve head
      (ONH) deformation and progressive retinal nerve fiber layer (RNFL) thinning for
      assessment of glaucoma progression. Algorithms for change analysis such as
      topographic change analysis and guided progression analysis perform event
      analysis of serial ONH surface height topology maps and RNFL thickness/RNFL
      retardance maps, respectively, providing a topographical display of the location
      of significant change. With spectral-domain OCT, it is feasible to delineate and
      measure the lamina cribrosa surface depth in addition to ONH surface depth and
      RNFL thickness. Growing evidence from experimental and clinical studies indicates
      that ONH and lamina cribrosa deformation can be observed prior to detectable RNFL
      thinning and functional loss in glaucoma. These findings lend support to the
      notion that upon detection of ONH/lamina cribrosa deformation, a time window for
      therapeutic intervention for better outcomes may exist. The ONH and the lamina
      cribrosa are therefore important targets for monitoring glaucoma progression.
      This review summarizes the latest findings comparing the performance of OCT,
      CSLO, and SLP for detection of progressive ONH and RNFL damages in glaucoma
      patients and the clinical implication and limitations of studying the
      morphological alteration of the ONH, lamina cribrosa, and RNFL in the assessment
      of glaucoma progression.

PMID- 29018669
TI  - Low vision aid-A ray of hope for irreversible visual loss in the pediatric age
      group.
AB  - PURPOSE: To analyze visual acuity (VA) improvement, causes of low vision (LV),
      and quality of life (QOL) following the use of low vision aids (LVAs) in children
      with LV. METHODS: A prospective analysis was conducted on children with LV aged
      between 4 years and 18 years between March 2013 and October 2013. Children were
      recruited from both urban schools and rural schools. LVAs were tried for visual
      improvement, and improved VA was noted. All children were trained to use the aid
      and followed up monthly for 3 consecutive months for VA improvement; QOL through
      a questionnaire was analyzed after the use of LVAs. RESULTS: A total of 74
      children (148 eyes; 50% male; mean age, 11.8 +/- 3.2 years) were analyzed, where
      34 children were recruited from rural areas and 40 from urban schools. After LVA
      use, 101 (68.24%) eyes of 59 (79.72%) children improved for distance with
      telescope and 81 (54.72%) eyes of 51 (68.91%) children improved for near with
      magnifiers. LV due to retinal problems, optic atrophy, congenital anomalies, and
      amblyopia drastically reduced after use of LVA. A statistically significantly
      higher proportion of children had either "excellent" or "good" QOL, and a
      significantly lower proportion of children had either "not satisfactory" or
      "poor" QOL after the use of LVA (p < 0.0001). CONCLUSION: LVA is essential and
      effective in improving VA and QOL in children with LV.

PMID- 29018668
TI  - Complex genetics of familial exudative vitreoretinopathy and related pediatric
      retinal detachments.
AB  - Familial exudative vitreoretinopathy (FEVR) is a hereditary vitreoretinal
      disorder that can cause various types of retinal detachments. The abnormalities
      in eyes with FEVR are caused by poor vascularization in the peripheral retina.
      The genetics of FEVR is highly heterogeneous, and mutations in the genes for Wnt
      signaling and a transcription factor have been reported to be responsible for
      FEVR. These factors have been shown to be the regulators of the
      pathophysiological pathways of retinal vascular development. Studies conducted to
      identify the causative genes of FEVR have uncovered a diverse and complex
      relationship between FEVR and other diseases; for example, Norrie disease, a
      Mendelian-inherited disease; retinopathy of prematurity, a multifactorial genetic
      disease; and Coats disease, a nongenetic disease, associated with pediatric
      retinal detachments.

PMID- 29018670
TI  - Short break-up time type dry eye has potential ocular surface abnormalities.
AB  - PURPOSE: To describe a case series in which corneal fluorescein staining (CFS)
      development occurred in short break-up time (s-BUT) dry eyes after a short period
      during prolonged opening of the eye. METHODS: The study was designed as a
      clinical case series. Ocular surface evaluations were performed on 13 individuals
      with s-BUT dry eye. Tear function examinations included Schirmer's test and BUT
      evaluation. RESULTS: In all 13 cases, the BUT was short, but the tear quantity
      was not so bad. In all cases, CFS developed following a single eye opening, and
      the staining was observed at sites that showed as dark spots. In several cases,
      the CFS disappeared later. CONCLUSION: In this study, we demonstrated that CFS
      could develop following a single eye opening. Based on our findings, CFS is a
      dynamic phenomenon rather than a stable indicator of ocular surface
      abnormalities. Moreover, s-BUT dry eye has the potential to show ocular surface
      abnormalities.

PMID- 29018671
TI  - Distribution of corneal and ocular spherical aberrations in eyes with cataract in
      the Taiwanese population.
AB  - PURPOSE: To investigate the distribution of corneal and ocular spherical
      aberrations (SAs) in eyes with cataract in the Taiwanese population. METHODS:
      Corneal and ocular SAs were measured in the central 6-mm optical zone using
      wavefront aberrometry. Axial length (AL) and keratometry (K) were also evaluated
      in each eye. RESULTS: A total of 413 eyes in 234 patients were analyzed. The mean
      age of the patients was 66.8 +/- 10.64 years. The mean AL and K values were 24.32
      mm and 44.08 D, respectively. The mean corneal SA was 0.307 +/- 0.135 MUm and
      ocular SA was -0.042 +/- 0.487 MUm. Ocular and corneal SAs were significantly
      correlated (r2 = 0.04, p < 0.001). Corneal and ocular SAs were not significantly
      correlated with K (p = 0.096 and p = 0.634, respectively), but were significantly
      correlated with AL (p < 0.001). Multilinear regression showed that corneal SAs
      and age were the dependent variables that predicted ocular SAs (r2 = 0.143, F =
      13.65, p < 0.01), especially in patients who were aged > 50 years, for whom a
      strongly significant positive correlation was found (r2 = 0.102, F = 11.10, p <
      0.001). CONCLUSION: Corneal and ocular SAs varied among cataract patients and
      correlated with AL. After 50 years of age, ocular SAs increased significantly
      because of an increase in internal (lenticular) SAs. Corneal SAs in Taiwanese
      patients were larger than those in Japanese patients and similar to those in
      Chinese and Malaysian populations. Preoperative measurement of wavefront
      aberrations is necessary to select which aspherical intraocular lenses are most
      suitable for achieving better postoperative visual quality.

PMID- 29018673
TI  - Development of macular holes in diabetic retinopathy with fibrovascular
      proliferation: Report of four cases.
AB  - There are yet no reports in the literature describing the mechanism of macular
      hole (MH) formation associated with fibrovascular proliferation in proliferative
      diabetic retinopathy. We report four cases of MHs in diabetic retinopathy with
      fibrovascular proliferation; formation of MHs were studied using sequential pre
      MH optical coherence tomography (OCT). In Case 1, initial OCT revealed tractional
      schisis and cysts with fovea detachment. An MH with bowl-shaped detachment was
      noted within 6 weeks. In Case 2, initial OCT revealed thickened posterior hyaloid
      membrane with vitreomacular traction. Five and a half years later, OCT showed MH
      formation with possible vitreomacular separation. Some epiretinal membrane was
      also noted in the macula area. In Case 3, initial OCT revealed tractional retinal
      elevation from the superonasal area to the fovea with macular thinning. An MH
      with detachment developed 7 weeks later. In Case 4, initial OCT revealed macula
      involved retinal detachment with traction. An MH was noted 4 weeks later. The
      analysis of sequential OCT findings in these four cases suggests that strong
      vitreoretinal adhesion and traction of fibrovascular proliferation may induce an
      MH without going through the same evolutionary phases as those characteristic of
      idiopathic MHs.

PMID- 29018672
TI  - Clinical characteristics and antivascular endothelial growth factor effect of
      choroidal neovascularization in younger patients in Taiwan.
AB  - BACKGROUND/PURPOSE: The purpose of this study is to share experiences diagnosing
      and treating choroidal neovascularization (CNV) in young patients (age <= 50
      years) at our hospital. METHODS: The study reviewed retrospective data of
      patients (<= 50 years old) with CNV who received antivascular endothelial growth
      factor treatment (anti-VEGF) between January 2007 and August 2012 at Shin Kong Wu
      Ho-Su Memorial Hospital. We recorded the total number of injections, types of
      drugs, preoperative and final best-corrected visual acuity (BCVA), central
      retinal thickness (CRT) in optical coherence tomography (OCT), and total follow
      up times, and then used two-tailed paired t tests to compare mean changes in BCVA
      and CRT on OCT. RESULTS: The study enrolled 59 patients <= 50 years of age with
      CNV diagnosed in 67 eyes. The mean age was 36.9 +/- 10.0 years (range, 8-50
      years). Twenty-one patients were male and 38 patients were female. Forty-two CNV
      lesions were subfoveal, 19 were juxtafoveal, and five were extrafoveal. The mean
      total follow-up time was 18.5 +/- 19.9 months (range, 0.5-71 months). Pathologic
      myopia was the most common cause of CNV in this study (47.8%), followed by
      punctate inner choroidopathy (17.9%), idiopathic CNV (16.4%), polypoidal
      choroidal vasculopathy (13.4%), angioid streaks (3.0%), and choroidal rupture
      (1.5%). After anti-VEGF treatment, the mean BCVA improved from 0.69 +/- 0.61 to
      0.42 +/- 0.59 (p < 0.05). CRT decreased from 257.5 +/- 48.2 to 210.3 +/- 35.7 (p
      < 0.05). The mean number of injections was 1.9 +/- 1.6 (range, 1-9). CONCLUSION:
      In this study we found that pathologic myopia, punctate inner choroidopathy, and
      idiopathic and polypoidal choroidal vasculopathy comprised the four most common
      causes of CNV in patients <= 50 years of age in Taiwan. We also revealed that
      anti-VEGF treatment is highly effective in the treatment of CNV in this age
      group.

PMID- 29018674
TI  - Detection of the progression of retinal nerve fiber layer loss by optical
      coherence tomography in a patient with glaucomatocyclitic crisis.
AB  - A 30-year-old man presented with glaucomatocyclitic crisis, also known as Posner
      Schlossman syndrome, and acute intraocular pressure elevation. Changes in the
      longitudinal retinal nerve fiber layer (RNFL) and the cup-to-disc (C/D) ratio of
      the optic disc were detected by Stratus optical coherence tomography (OCT). The
      average RNFL thickness in the affected eye was greater than that in the
      unaffected eye on Day 3 (132.99 MUm, C/D ratio: 0.24 vs. 105 MUm, C/D ratio:
      0.26). However, the RNFL thickness continued to decrease and the C/D ratio
      progressively increased in the affected eye over 12 months (60 MUm, C/D ratio:
      0.67), although the intraocular pressure was controlled at <21 mmHg during that
      period. Glaucomatous visual field defects were also found. A progressive decrease
      in the thickness of the RNFL was demonstrated by Stratus optical coherence
      tomography following an elevation in the acute intraocular pressure in the
      patient. Prompt treatment and longitudinal monitoring are necessary to prevent
      and detect glaucomatous damage.

PMID- 29018675
TI  - Bilateral inferior oblique muscle paresis after posterior subtenon injection of
      triamcinolone acetonide.
AB  - Posterior subtenon injections of steroidal drugs are commonly used to treat
      various chorioretinal inflammatory diseases. Subsequent strabismus is rare, but
      it is associated with severe visual disturbance when present. We report a case of
      simultaneous bilateral inferior oblique muscle paresis in a 60-year-old man who
      developed it after receiving intravitreal injections of bevacizumab and posterior
      subtenon injections of triamcinolone acetonide for the treatment of diabetic
      macular edema. The patient complained of excessive pain during the injections,
      which were performed at the 6 o'clock position in both eyes. According to the
      literature, inferior oblique muscle paresis after posterior subtenon injections
      is rare. This complication may be prevented by proper selection of the injection
      site and paying attention to any unusual patient complaints during the procedure.

PMID- 29018676
TI  - Stevens-Johnson syndrome following cataract surgery.
AB  - A case of Stevens-Johnson syndrome in a healthy 58-year-old woman who underwent
      cataract surgery under topical anesthesia is reported. General skin erosions
      developed 2 hours after surgery. The patient's family doctor diagnosed that she
      was allergic to seafood. One month later, she underwent phacoemul-sification
      surgery in the other eye. After surgery, she developed Stevens-Johnson syndrome
      with general skin lesions, erythema nodosa, genital mucosa erosion, oral ulcers,
      gastritis, and conjunctiva edema. The symptoms subsided 2 weeks later after
      immunotherapy. Although nonpreserved anesthesia (2% lidocaine) has seldom been
      reported to cause allergic reactions via the intravenous or the intramuscular
      route, it is possible that an intracameral injection of 0.2% lidocaine during
      cataract surgery can induce Stevens-Johnson syndrome. Careful evaluation of the
      patient's history and proper treatment were recommended to prevent additional
      complications.

PMID- 29018677
TI  - Ocular adnexal lymphoma: Five case reports and a literature review.
AB  - This article reports the clinical course and treatment of ocular adnexal lymphoma
      based on a retrospective review of five cases with a histologically approved
      ocular adnexal lymphoma at Kaohsiung Veterans General Hospital over 10 years.
      Extranodal B-cell lymphoma in the orbit, lacrimal gland, eyelid, or conjunctiva
      was found in these patients. Four of them were female, and they were aged 45-64
      years. All patients were also consulted with hematologists for possible systemic
      involvement and therapeutic plan. The patient with retrobulbar and orbital apex
      involvement received systemic chemotherapy. The patient with lacrimal gland
      involvement experienced tumor recurrence after local excision, and therefore
      received adjuvant radiotherapy. The remaining three patients had localized
      lymphoma on the eyelid or bulbar conjunctiva, and they all showed no recurrence
      after surgical excision. The incidence of ocular adnexal lymphoma has risen
      worldwide over the last few decades. Although most cases are confined to ocular
      adnexal, some may also be associated with disseminated lymphoma. Accurate
      diagnosis and staging is mandatory for appropriate treatment. Generally speaking,
      localized and low-grade ocular adnexal lymphoma involved eyelid or conjunctiva
      seem to have good outcome after surgical excision only. Systemic chemotherapy
      should be considered in patients with advanced disease or systemic
      manifestations, and radiotherapy also offers a good choice for lacrimal gland
      lymphoma.

PMID- 29018678
TI  - Latest advances in the treatment of corneal diseases.

PMID- 29018679
TI  - Rod metabolic demand drives progression in retinopathies.
AB  - Various factors are thought to cause the development and progression of disease
      in macular degeneration, diabetic retinopathy, and retinitis pigmentosa. Some of
      the deleterious processes include oxidative stress, hypoxia, metabolic
      derangement, genetics, and vasculopathy. In this review, we present a unified
      theory for the pathophysiology of several retinopathies based on the unique and
      intense metabolism of rod photoreceptors.

PMID- 29018680
TI  - Autologous serum therapy in recalcitrant laser-assisted in situ keratomileusis
      induced neurotrophic epitheliopathy.
AB  - BACKGROUND/PURPOSE: To evaluate the efficacy of autologous serum eye drops for
      patients with recalcitrant laser-assisted in situ keratomileusis (LASIK)-induced
      neurotrophic epitheliopathy (LINE) unresponsive to conventional treatment, and to
      determine the possible predisposing risk factors of these patients. METHODS: We
      enrolled 10 consecutive patients (20 eyes) undergoing femtosecond-assisted myopic
      LASIK surgery presenting with recalcitrant LINE for > 1 year. Another 340
      patients (713 eyes) receiving femtosecond-assisted myopic LASIK without
      recalcitrant LINE were set as controls. Possible risk factors associated with
      recalcitrant LINE were investigated. Twenty percent autologous serum treatment
      was prescribed to 20 eyes. The efficacy of autologous serum was assessed with
      ocular surface conditions, tear function, and the change of best-corrected visual
      acuity. RESULTS: Age older than 30 years [odds ratio (OR) = 7.74; 95% confidence
      interval (CI), 1.74-34.50], flap thickness < 110 MUm (OR = 3.47; 95% CI, 1.22
      9.73), and a flap diameter < 8.5 mm (OR = 5.38; 95% CI, 1.95-14.85) pose higher
      risks in femtosecond laser-assisted myopic LASIK. All eyes (100%) achieved
      remission after autologous serum treatment. The visual acuity before treatment
      was 0.49 +/- 0.41 in LogMAR, and the visual acuity after treatment was 0.14 +/-
      0.22 in LogMAR. Time to achieve remission was 8.26 +/- 11.87 weeks. Mean relapse
      free survival after discontinuing autologous serum was 47 weeks. CONCLUSION: Risk
      factors of recalcitrant LINE in femtosecond laser-assisted myopic LASIK were
      identified as older age, a thinner flap (<110 MUm), and a small flap diameter
      (<8.5 mm). Autologous serum eye drops can effectively improve corneal surface
      conditions and postoperative visual acuity.

PMID- 29018681
TI  - Suture pull-through insertion of graft donor in Descemet stripping automated
      endothelial keratoplasty: Results of 4-year follow-up.
AB  - PURPOSE: To report our clinical experience and 4-year follow-up results of
      Descemet stripping automated endothelial keratoplasty (DSAEK) with the suture
      pull-through insertion technique. METHODS: This is a retrospective study of 195
      eyes in which a posterior lamellar keratoplasty was performed between 2007 and
      2011. The insertion of a folded donor lenticule was performed with a double-armed
      10-0 suture using a straight transchamber needle and half-circle needle.
      Endothelial cell density was measured annually up to 4 years after the surgery,
      and cell loss was calculated based on the median preoperative donor endothelial
      cell density. Postoperative complications, primary graft failure, pupillary
      block, and dislocation of the donor tissue were assessed. RESULTS: All patients
      underwent uncomplicated DSAEK. Data were available for 195 eyes (100%) at 1 year,
      186 eyes (95.3%) at 2 years, 176 eyes (90.2%) at 3 years, and 160 eyes (82%) at 4
      years. Median preop-erative donor endothelial cell density was 2688 cells/mm2
      [interquartile range (IQR) 207.5 cells/mm2], which decreased by 27% at 1 year
      (1956 cells/mm2, IQR 264.8 cells/mm2), 31% at 2 years (1855 cells/mm2, IQR 320.5
      cells/mm2), 35% at 3 years (1756.5 cells/mm2, IQR 306.5 cells/mm2), and 36% at 4
      years (1709.5 cells/mm2, IQR 288,0 cells/mm2). Nine patients (4.6%) had a
      dislocation of donor tissue; all were successfully reattached with a second air
      injection. Only three eyes (1.5%) developed graft failure. Pupillary block was
      present in 15 eyes (7.7%). CONCLUSION: DSAEK with suture pull-through insertion
      of donor graft represents a simplified and safe technique that has endothelial
      cell loss comparable with other techniques and low rates of intraoperative and
      postoperative complications.

PMID- 29018682
TI  - Comparison of trabeculectomy with Ex-PRESS shunt implantation in primary-open
      angle-glaucoma patients: A retrospective study.
AB  - PURPOSE: To investigate the efficacy of intraocular pressure (IOP) control and
      medication use over time after trabeculectomy (TRBC) and Ex-PRESS shunt
      implantation in primary-open-angle-glaucoma (POAG) patients. DESIGN:
      Retrospective case series. PATIENTS AND METHODS: A total of 33 unilateral POAG
      patients were enrolled, and 17 patients received traditional TRBC and 16 patients
      received Ex-PRESS device implantation. Data on IOP, reduction of antiglaucoma
      medication, and major complications were collected and analyzed after 12 months
      of follow up. RESULTS: After 12 months of follow up, both groups showed good IOP
      control. The mean preoperative IOP decreased from 38.5 (+/-6.9) to 18.2 (+/-11)
      mmHg after TRBC, and from 38.5 (+/-9.1) to 19.53 (+/-12.36) mmHg after Ex-PRESS
      implantation (both p < 0.05). The mean number of antiglaucoma medications
      prescribed at the last follow up decreased from 3.2 (+/-0.5) preoperatively to
      1.2 (+/-1.4) after TRBC versus 3.3 (+/-0.7) preoperatively to 1 (+/-0.9) after Ex
      PRESS implantation (both p < 0.05). Complete success rate (defined as no
      medication after surgery with IOP >5 and <18 mmHg) and qualified success rate
      (defined as with or without medication after surgery with IOP >5 and <18 mmHg)
      were similar (47% vs. 43% and 76.47% vs. 75%) between the two groups without
      statistical difference (p > 0.05). However, postoperative hypotony rate was more
      frequent after Ex-PRESS (37.5%) than after TRBC (17.64%). DISCUSSION: TRBC and Ex
      PRESS implantation provided similar IOP control and reduction of postoperative
      medication with low incidence of postoperative complications at intermediate-term
      follow up. However, the Ex-PRESS implantation device may last longer but with
      extra costs. It is up to the surgeon to decide which procedure to use according
      to the patient's situation and economic circumstances.

PMID- 29018683
TI  - Changes of intraocular pressure and refractive status in children following
      cycloplegic refraction with 1% cyclopentolate and 1% tropicamide.
AB  - PURPOSE: To evaluate the effect of cycloplegic mydriasis with 1% cyclopentolate
      and 1% tropicamide on the intraocular pressure (IOP) and refractive status of
      children for cycloplegic refraction and compare the [OP and refractive changes
      between hyperopic and myopic groups. METHODS: This study was designed as a
      retrospective cohort study. Ninety one children received cycloplegic mydriasis.
      The IOP was measured with a noncontact tonometer before cycloplegic
      administration. One drop of 1% cyclopentolate was administered, which was
      followed by two drops of 1% tropicamide at an interval of 10 minutes. The IOP was
      then measured 30 minutes after tropicamide instillation. Autorefraction was
      assessed with an autorefractometer before and after cycloplegic mydriasis.
      RESULTS: The mean age of the 44 girls and 47 boys was 7.3 +/- 2.4 years. The mean
      precycloplegic IOP was 14.45 +/- 2.47 mmHg and the mean postcycloplegic IOP was
      15.06 +/- 3.08 mmHg in all eyes. A significant difference was noted in the IOP
      change (p = 0.033). In the 39 hyperopic eyes, the mean precycloplegic IOP and
      postcycloplegic IOP were 14.54 +/- 2.53 mmHg and 15.69 +/- 3.35 mmHg,
      respectively. There was a significant difference in the IOP change (p = 0.008).
      In the 52 myopic eyes, the mean precycloplegic IOP and postcycloplegic IOP were
      14.38 +/- 2.44 mmHg and 14.61 +/- 2.80 mmHg, respectively (p = 0.72). There was
      no significant IOP change in the myopic group. The postcycloplegic IOP was
      significantly different between the hyperopic and the myopic groups (p = 0.021).
      Three eyes (3.3%) had an IOP elevation more than 5.0 mmHg after cycloplegic
      mydriasis. Postcycloplegic refraction showed significant hyperopic shifts in all
      eyes (p < 0.0001). CONCLUSION: Cycloplegic mydriasis with 1% cyclopentolate and
      1% tropicamide caused IOP changes in preschool and school-aged children with
      hyperopia. Ophthalmologists should be very cautious in monitoring IOP changes for
      children with cycloplegic medication use.

PMID- 29018684
TI  - Rescue effects of intravitreal aflibercept in the treatment of neovascular age
      related macular degeneration.
AB  - We report the rescue results of intravitreal aflibercept in patients with
      treatment-resistant neovascular age-related macular degeneration (AMD). We
      retrospectively analyzed eyes with neovascular AMD resistant to posterior
      subtenon triamcinolone, intravitreal ranibizumab, and/or bevacizumab treatment in
      a tertiary medical center in middle Taiwan between December 2013 and October
      2014. We then switched treatment to 2.0 mg aflibercept. The main outcome included
      changes in best-corrected visual acuity and central foveal thickness measured by
      optical coherence tomography during monthly follow-up. There were 204 patients
      with neovascular AMD, and the percentage of refractory cases was 1.96% (4 of 204
      cases). Our study included five eyes of four patients that were resistant to
      multiple treatments and subsequently switched to aflibercept. The mean age was
      71.25 +/- 11.09 years (range 57-83 years). Treatments were on average 6.6 times
      previously. Upon switching to aflibercept treatment, the average central foveal
      thickness on optical coherence tomography was 505.6 +/- 270.86 MUm (range 150-815
      MUm). After aflibercept treatment, the average central foveal thickness was 192
      +/- 51.76 MUm (range 149-274 MUm). All patients showed anatomic improvement, and
      80% of the eyes (4 of 5 eyes) had improved best-corrected visual acuity and 20%
      of the eyes (1 of 5 eyes) had stable visual acuity. Patients tolerated the
      treatment well without serious adverse events. This short-term study showed that
      intravitreal aflibercept was effective and safe in treatment-resistant
      neovascular AMD cases. However, analysis of more cases and long-term follow-ups
      are mandatory.

PMID- 29018685
TI  - Easy-to-prepare autologous platelet-rich plasma in the treatment of refractory
      corneal ulcers.
AB  - As platelets are rich in growth factors for tissue regeneration, autologous
      platelet-rich plasma (PRP) has been used to treat some refractory corneal
      defects. Although PRP is effective, the cost of its preparation is very high.
      This article presents three cases of refractory corneal ulcer under the
      prescription of autologous PRP. The autologous PRP used in these cases was easily
      prepared in the blood bank laboratory. In this paper, we collected three patients
      with refractory corneal ulcer who were unresponsive to conventional treatment.
      The patients presented with neurotrophic ulcer, exposure corneal ulcer, and
      limbal deciency with corneal ulcer after hepatitic keratitis. Although we easily
      prepared autologous PRP eye drops using simple laboratory centrifugation, this
      preparation still had a clinical effect on corneal defect. The mean intervention
      time was 24 +/- 6.9 days. The case with exposure corneal ulcer had significant
      wound healing and the other two cases felt subjective symptom relief. There were
      some clinical improvements of refractory corneal ulcers in our three cases. We
      present the clinical results of three cases and report an easy procedure for the
      preparation of autologous PRP. Autologous PRP prepared simply in the laboratory,
      it may be an alternative option for treating refractory corneal ulcer.

PMID- 29018686
TI  - Occult Descemet's membrane detachment after phacoemulsification surgery mimicking
      pseudophakic bullous keratopathy.
AB  - We herein report two cases of occult Descemet's membrane detachment (DMD) after
      phacoemulsification surgery, which initially presented as persistent corneal
      edema and had been considered as pseudophakic bullous keratopathy. The patients
      were thus scheduled to receive corneal transplantation. For Case 1, DMD was
      incidentally detected by slit-lamp examination 2 months postoperatively, only
      when part of the cornea became clearer. For Case 2, anterior segment optical
      coherence tomography demonstrated extensive DMD, which had lasted 5 months after
      the operation. DMDs in both patients had been successfully attached after
      descemetopexy. Occult DMD should be suspected in patients with persistent severe
      corneal edema after phacoemulsification surgery. Corneal transplantation may be
      avoided by timely diagnosis and treatment of DMD.

PMID- 29018687
TI  - Ocular post-transplant lymphoproliferative disorder.
AB  - We report a case of an iris tumor with muttonfat keratic precipitates in a young
      patient after liver transplantation surgery. A 6yearold girl underwent liver
      transplantation for congenital biliary atresia and was subsequently
      immunosuppressed with oral cyclosporine. We examined her 5 years after
      transplantation because of a "white nodule in her left eye," which had been
      detected by her father one day before visiting our clinic. Ophthalmological
      examinations revealed symmetric visual acuity and normal afferent papillary
      reflex. Slitlamp examination revealed a depigmented iris nodule approximately3 *
      2 mm with muttonfat keratic precipitates in the anterior chamber. Fundus
      examination was unremarkable, and computed tomography (CT) of the head, neck, and
      abdomen showed normal findings. Based on the suspicion of post-transplant
      lymphoproliferative disorder (PTLD), therapy was initiated, which included
      tapering cyclosporine and topical mydriatics. After 2.5 months, the lesion
      resolved and no more muttonfat keratic precipitates were identified in the
      anterior chamber. In this PTLD case, the patient presented with an iris nodule
      and muttonfat keratic precipitates, and the ocular PTLD presentation resolved
      spontaneously after tapering cyclosporine.

PMID- 29018688
TI  - Retinal detachment with a break at pars plicata associated with congenital
      malformation of the lens-zonule-ciliary body complex.
AB  - Retinal detachment with a break at the pars plicata associated with congenital
      malformation of lens-zonule-ciliary body complex is rare; most reports are of
      young Japanese male patients with atopic dermatitis. The present case report is
      the first to describe the condition in a Chinese patient with no atopic
      dermatitis or trauma history. A 22-year-old male presented with blurred vision in
      the left eye for 4 months. Fundus examination revealed shallow lower temporal
      retinal detachment. Further examination with scleral indentation under maximal
      pupil dilatation identified a break at the far periphery beyond the ora serrata
      and pars plana. Gonioscopy revealed a pars plicata break at the nonpigmented
      ciliary epithelium associated with congenital ciliary process hypoplasia and
      subtle lens defect at the same meridian. The retina was successfully reattached
      after segmental scleral buckling, cryopexy, and laser photocoagulation.

PMID- 29018689
TI  - Choose the right treatment for the right patients.

PMID- 29018690
TI  - When is macular edema not macular edema? An update on macular telangiectasia type
      2.
AB  - Macular telangiectasia type 2 (Mac Tel 2) also known as idiopathic perifoveal
      telangiectasia and juxtafoveolar retinal telangiectasis type 2A is an enigmatic
      disease of unknown etiology. It manifests both neurodegenerative and
      vasculopathic characteristics. It manifests itself during the fifth or sixth
      decades of life. Clinical characteristics include minimally dilated parafoveal
      capillaries with loss of the retinal transparency in the area involved, absence
      of lipid exudation, right-angled retinal venules, superficial retinal refractile
      deposits, hyperplasia of the retinal pigment epithelium (RPE), foveal atrophy and
      subretinal neovascularization (SRNV). Optical coherence tomography (OCT) images
      typically demonstrate outer retinal abnormalities and the presence of intra
      retinal hyporeflective spaces that are usually not related with retinal
      thickening or fluorescein leakage. The typical fluorescein angiographic finding
      is a deep intraretinal hyperfluorescent staining in the temporal parafoveal area.
      With time this fluorescein hyperfluorescence involves the whole parafoveal area
      but does not extend to the center of the fovea. Long-term prognosis for central
      vision is poor, because of the development of SRNV or macular atrophy. Its
      pathogenesis remains unclear but multi-modality imaging with fluorescein
      angiography, spectral domain OCT, adaptive optics, confocal blue reflectance,
      short wave fundus autofluorescence, OCT angiography, and clinicopathological
      correlations implicate Muller cells. Currently there is no known treatment for
      this condition.

PMID- 29018692
TI  - Refractive error, visual acuity, and corneal-curvature changes in high and low
      myopes with orthokeratology treatment: A Malaysian study.
AB  - BACKGROUND/PURPOSE: The effect of orthokeratology (OK) on low myopia is well
      known, but there are a few reports on its effect on high myopia. In this study,
      the parametric changes in high and low myopia as results of wearing OK lenses for
      a period of 6 months have been analyzed. METHODS: Records of schoolchildren (age
      7-17 years) undergoing OK treatment from an optometry clinic were retrospectively
      reviewed. Data involving refractive errors, uncorrected visual acuity, and
      corneal curvatures at baseline and after 1 day, 1 week, 1 month, 3 months, and 6
      months of OK treatment from 25 patients who fulfilled the inclusion criteria were
      examined. For the analysis, the participants were arbitrarily divided into two
      groups comprising high myopia (< -6.00 D) and low to moderate myopia (from -1.00
      D to -6.00 D). RESULTS: Significant reductions of refractive error, improvement
      in visual acuity, and corneal-curvature flattening were found in all participants
      after 6 months of OK lens wear compared to the baseline. No significant changes
      were found in corneal toricity in both high and low to moderate myopic groups.
      Almost all of these occurred after one night of lens wear in both the high- and
      low-myopia groups. CONCLUSION: The OK lens wear significantly reduced the
      refractive error and corneal curvature that results in the improvement in visual
      acuity in both high- and low-myopia groups, and the reduction seemed to occur
      nearly at the same time despite the difference in initial myopic power. High
      myopes with refractive power up to -8.25 D would benefit significantly from OK
      lenses.

PMID- 29018691
TI  - Immunosuppressive therapy for eye diseases: Effectiveness, safety, side effects
      and their prevention.
AB  - Ocular inflammation is a significant cause of ocular morbidity and visual
      impairment. Topical, periocular, intraocular, and systemic corticosteroids are
      highly effective for treating appropriate forms of ocular inflammation. However,
      their use may be constrained by local and/or systemic side effects, especially if
      long-term therapy is required. As a result, immunosuppressive agents increasingly
      have been used to manage ocular inflammation alongside or in place of
      corticosteroids. The four categories of agents used today are antimetabolites
      [primarily methotrexate, mycophenolate mofetil (MMF), and azathioprine]; T-cell
      inhibitors (usually cyclosporine, less often tacrolimus or sirolimus); alkylating
      agents (cyclophos-phamide and chlorambucil); and biologic agents [tumor necrosis
      factor (TNF) inhibitors, lymphocyte inhibitors, and interleukin inhibitors]. The
      primary goals of immunosuppressive therapy are (1) to control inflammation when
      corticosteroids fail to do so; (2) to prevent corticosteroid-induced toxicity
      when the necessary corticosteroid dosage exceeds the desired or safe level
      (corticosteroid sparing); and (3) to treat specific high-risk uveitis syndromes
      known to respond poorly to corticosteroids alone. Growing evidence shows the
      effectiveness of immunosuppressive drugs in achieving these goals, as well as
      improved visual function, prevention of ocular complications, and in some cases
      even disease remission. However, these agents also have side effects, which must
      be considered in each patient's management. In this report, we summarize the
      effectiveness and safety of immunosuppressive drug therapy utilized in the
      treatment of ocular inflammatory diseases.

PMID- 29018694
TI  - Prevalence of general binocular dysfunctions among rural schoolchildren in South
      Korea.
AB  - BACKGROUND/PURPOSE: To assess the prevalence of nonstrabismic accommodative and
      vergence dysfunctions among primary schoolchildren in Hampyeong, a rural area of
      South Korea. METHODS: Five hundred and eighty-nine primary schoolchildren, 8-13
      years old, were each given a thorough eye examination, including binocular-vision
      testing, near point of convergence, horizontal phoria measurement by von Graefe,
      and negative and positive vergence amplitudes with prism bar, to determine any
      form of accommodative or vergence dysfunctions. RESULTS: Of the 589 participants
      examined, 168 (28.5%) primary schoolchildren presented some form of nonstrabismic
      accommodative or vergence dysfunctions. The prevalence of accommodative
      dysfunctions and vergence dysfunctions was 13.2% and 9%, respectively.
      Convergence insufficiency (10.3%) was more prevalent than convergence excess
      (1.9%), and accommodative insufficiency (5.3%) was more prevalent than
      accommodative excess (1.2%). CONCLUSION: This study suggests that nonstrabismic
      accommodative and vergence dysfunctions are prevalent in the rural area of South
      Korean primary schoolchildren, and convergence insufficiency was the most
      prevalent.

PMID- 29018693
TI  - Axial length and subfoveal choroidal thickness in individuals with age-related
      macular degeneration.
AB  - PURPOSE: To compare axial length (AL) and subfoveal choroidal thickness (SFCT)
      between individuals with age-related macular degeneration (AMD) and controls with
      no lesions. METHODS: This was a case-control study. In total, 853 eyes of 484
      patients (>65 years), including 397 eyes at various AMD stages and 456 eyes with
      no fundus lesions (controls) were recruited. Using color fundus photography, eyes
      were grouped according to AMD degree. AL was automatically measured using IOL
      Master and SFCT was manually measured by two independent observers. The
      associations among age, AL, SFCT, and each AMD grade were analyzed. RESULTS: Out
      of 853 eyes, 456 had no lesions, 217 contained drusen only, 134 had early AMD,
      and 46 had late AMD. The eyes with late AMD were older (p = 0.007) and had longer
      AL (p >= 0.001) and thinner SFCT (p < 0.001) compared with groups of no fundus
      lesions, drusen only, and early AMD. SFCT in eyes with late AMD decreased by
      19.20 MUm (p = 0.049), 24.78 MUm (p = 0.029), and 15.56 MUm (p = 0.162) compared
      with groups of no fundus lesions, drusen only, and early AMD, respectively. SFCT
      decreased by 14.18 MUm/mm increase in AL (p < 0.001). The odds ratio (OR) for
      late AMD by longer AL (>=25 mm) and thinner SFCT (<240 MUm) was 4.54 (chi2 =
      9.36; p = 0.002) and 4.86 (chi2 = 17.62; p < 0.001), respectively, and was 9.57
      (chi2 = 18.07; p < 0.001) when both AL >= 25 >=m and SFCT < 240 MUm. CONCLUSION:
      Eyes with late AMD have distinct reduced SFCT and elongated AL. Eyes with thinner
      SFCT and longer AL showed high ORs for late AMD and even higher ORs when both
      factors were simultaneously present. These findings illustrate the crucial
      pathophysiological role of these two important ocular fac tors and arouse our
      attention to patients with both characteristics, especially in Asian countries
      where the prevalence of myopia are disturbingly high.

PMID- 29018695
TI  - Negative Mantoux test in a patient with definite pulmonary and ocular
      tuberculosis.
AB  - The case is reported of a patient with pulmonary and ocular tuberculosis
      presenting with blurred vision in both eyes. A 27-year-old well-nourished male
      nursing-home resident with a previous history of traumatic intracerebral
      hemorrhage was brought to the ophthalmological clinic due to progressively
      blurred vision. His best-corrected visual acuity was 20/400 in the right eye with
      only light perception in the left eye. Fundus examinations revealed retinal
      segmental periphlebitis and hemorrhagic retinitis in the right eye and dense
      vitreous hemorrhage in the left eye. The Mantoux test was negative; however, the
      results of an interferon gamma release assay were positive. Ocular tuberculosis
      was suspected. Although he had never had any respiratory symptoms, his chest
      radiograph and computed tomography scan showed a multiple centrilobular glandular
      and ground-glass appearance with air-space consoli dations and atelectasis in
      both lower lobes. Pulmonary tuberculosis was confirmed by a positive acid-fast
      stain of a bronchial alveolar lavage sample. A GEN-PROBE amplified Mycobacterium
      tuberculosis direct test of the vitreous fluids was also positive. Ocular
      tuberculosis was confirmed. After treatment for tuberculosis and vitrectomies,
      his final best-corrected visual acuity improved to 20/30 in the right eye and
      20/200 in the left eye. Ocular tuberculosis is rarely reported as the primary
      presentation of systemic tuberculosis in young patients. A negative Mantoux test
      may lead to misdiagnosis and delayed treatment. Doctors should become more
      familiar with the manifestations of systemic tuberculosis and use advanced
      diagnostic tools in cases of clinical suspicion.

PMID- 29018696
TI  - Bilateral uveitis associated with concurrent administration of rifabutin and
      nelfinavir.
AB  - Rifabutin-associated uveitis has been recognized as a dosage-dependent side
      effect. Previous studies have reported that clarithromycin or fluconazole may
      elevate concentrations of rifabutin through inhibition of metabolism through the
      cytochrome P-450 pathway. Nelfinavir is a protease inhibitor widely used in the
      treatment of human immunodeficiency virus (HIV) infection. The interactions
      between protease inhibitors and rifabutin have not been reported in clinical
      practice. Therefore, we present a case of bilateral uveitis associated with
      coadministration of rifabutin and nelfinavir. Uveitis did not subside until
      discontinuation of rifabutin. To our knowledge, this is the first report of
      uveitis with concurrent administration of rifabutin and nelfinavir. Our finding
      reminds us that rifabutin dosage should be reduced when it is administered with
      protease inhibitors.

PMID- 29018697
TI  - Varicella zoster virus-associated neuroretinitis.
AB  - Varicella zoster virus-associated neuroretinitis is rare. We report a patient who
      presented with blurred vision of the left eye and extraocular movement pain. A
      fundoscopic examination revealed disc edema, hyperemia, and macular edema. The
      impression was neuroretinitis. Intravenous methylprednisolone pulse therapy was
      administered. However, visual recovery was incomplete with optical coherence
      tomography (OCT) imaging showing photoreceptor layer disruption. The laboratory
      data were rechecked and demonstrated a high varicella zoster virus immunoglobulin
      G titer. Varicella zoster virus-associated neuroretinitis was suspected and oral
      acyclovir was prescribed. His visual acuity improved to 0.9 after 2 weeks of
      treatment, and OCT showed photoreceptor layer restoration. Spectrum-domain OCT
      provides useful information when evaluating the disease course of neuroretinitis.

PMID- 29018698
TI  - Rapid anterior capsular phimosis after cataract surgery in a patient with chronic
      angle closure glaucoma.
AB  - We report a case of complete occlusion of capsulorrhexis opening in a patient
      with chronic angle closure glaucoma with fixed-dilated pupil in the following 2
      weeks after an uneventful cataract surgery. The capsulorrhexis diameter was
      intended to make between 5.0 mm and 5.5 mm, to prevent photophobia afterward.
      There was no evidence of zonular weakness on preoperative examination or during
      the surgery. Nd:YAG anterior capsulotomy was performed for capsular phimosis and
      to enlarge capsulorrhexis. The patient regained her visual acuity 3 days after
      laser treatment, and no pseudophakodonesis, intraocular lens decentration, and re
      phimosis were noted at the 3-month follow-up.

PMID- 29018699
TI  - Ocular decompression retinopathy after laser iridotomy in a patient with acute
      angle closure.
AB  - A 65-year-old female developed elevated intraocular pressure (IOP) with angle
      closure in the right eye. The fundus examination revealed vitreo-retinal
      hemorrhage that had occurred after neodymium-doped yttrium aluminum garnet
      (Nd:YAG) laser iridotomy. The retinal hemorrhage resolved spontaneously. This is
      a rare complication that occurs when the IOP is lowered rapidly. Ocular
      decompression retinopathy (ODR) was identified. We reviewed several cases of ODR
      that were treated by various interventions. We also discuss the possible
      pathogenesis, prognosis, and treatment strategy.

PMID- 29018700
TI  - Sub-internal limiting membrane hemorrhage treated with intravitreal tissue
      plasminogen activator followed by octafluoropropane gas injection.
AB  - Sub-internal limiting membrane (sub-ILM) hemorrhage is a relatively rare disease
      which is associated with different etiologies and often leads to loss of visual
      acuity. We report two cases of sub-ILM hemorrhage, both confirmed by optical
      coherence tomography (OCT) and treated with an intravitreal injection of tissue
      plasminogen activator (tPA) followed by an octafluoropropane (C3F8) pneumopexy
      and a strict postoperative prone positioning. The hemorrhage was totally resolved
      and complete visual recovery was achieved in both cases. We found tPA hemolysis
      with C3F8 pneumopexy to be a safe and effective method for treating sub-ILM
      hemorrhage.

PMID- 29018701
TI  - The use of macular optical coherence tomography thickness in the diagnosis and
      follow-up of glaucoma.

PMID- 29018702
TI  - Macular thickness analysis for glaucoma diagnosis and management.
AB  - There is increasing literature regarding the role of macular imaging by optical
      coherence tomography (OCT) in glaucoma care. Spectral domain OCT (SD-OCT) has
      allowed for high resolution imaging of the total macula and macular segments.
      With the use of asymmetry analysis, macular thickness is a measurement that can
      be used for the detection and progression of glaucoma. Some artifacts seen on
      retinal nerve fiber layer (rNFL) scans may be overcome by macular SD-OCT imaging.
      Also, nonglaucomatous optic neuropathies may be more easily identified on macular
      thickness plots than rNFL scans. Special populations, such as children or myopes,
      may also have improved glaucoma surveillance using macular SD-OCT. In this review
      we explore the advantages and pitfalls of macular OCT in glaucoma care and offer
      an approach on how to use macular thickness scans in clinical practice.

PMID- 29018703
TI  - Retinal complications associated with congenital optic disc anomalies determined
      by swept source optical coherence tomography.
AB  - Optical coherence tomography has evolved over the past 2 decades to be an
      important ancillary method to evaluate diseases of the anterior and posterior
      segments of the eye. The more recent development of swept-source optical
      coherence tomography (SS-OCT) with a wavelength-tunable laser centered at 1050 nm
      and deeper imaging depth of 2.6 mm has enabled clinicians to evaluate congenital
      optic disc anomalies including optic disc pits, optic disc colobomas, and morning
      glory syndrome in more detail. The SS-OCT findings of the posterior precortical
      vitreous pocket, Cloquet's canal, lamina cribrosa that is torn from the
      peripapillary sclera, and the retrobulbar subarachnoid space immediately
      posterior to the highly reflective tissue lining the bottom of the excavation are
      presented. In addition, abnormal communications between the vitreous cavity and
      the subretinal and subarachnoid spaces in eyes with congenital optic disc
      anomalies are also reviewed. The retinal complications associated with congenital
      optic disc anomalies are treated by vitreous surgery, silicone oil tamponade, and
      peripapillary laser photocoagulation or scleral buckling. However, the surgical
      outcomes are limited and not entirely satisfactory. Analyses by SS-OCT of
      congenital optic disc anomalies should make the treatment correspond better with
      the pathological findings.

PMID- 29018704
TI  - Comparison of glaucoma diagnostic accuracy of macular ganglion cell complex
      thickness based on nonhighly myopic and highly myopic normative database.
AB  - BACKGROUND/PURPOSE: To evaluate and compare the diagnostic discriminative ability
      for detecting glaucoma in highly myopic eyes from a normative database of macular
      ganglion cell complex (mGCC) thickness based on nonhighly myopic and highly
      myopic normal eyes. METHODS: Forty-nine eyes of 49 participants with high myopia
      (axial length >= 26.0 mm) were enrolled. Spectral-domain optical coherence
      tomography scans were done using RS-3000, and the mGCC thickness/significance
      maps within a 9-mm diameter circle were generated using built-in software. We
      compared the difference of sensitivity, specificity, and diagnostic accuracy
      between the nonhighly myopic database and the highly myopic database for
      differentiating the early glaucomatous eyes from the nonglaucomatous eyes.
      RESULTS: This study enrolled 15 normal eyes and 34 eyes with glaucoma. The mean
      mGCC thickness of the glaucoma group was significantly less than that of the
      normal group (p < 0.001). Sensitivity was 96.3%, and the specificity was 50.0%
      when using the nonhighly myopic normative database. When the highly myopic
      normative database was used, the sensitivity was 88.9%, and the specificity was
      90.0%. The false positive rate was significantly lower when using the highly
      myopic normative database (p < 0.05). CONCLUSION: The evaluations of glaucoma in
      eyes with high myopia using a nonhighly myopic normative database may lead to a
      frequent misdiagnosis. When evaluating glaucoma in high myopic eyes, the mGCC
      thickness determined by the long axial length high myopic normative database
      should be applied.

PMID- 29018705
TI  - Correlation of spectral domain optical coherence tomography findings in sub
      silicone oil foveal depression space and visual outcome in eyes undergoing
      silicone oil removal.
AB  - BACKGROUND/PURPOSE: To describe small hyper-reflective spherical bodies in sub
      silicone oil-foveal depression (SSO-FD) space using spectral domain optical
      coherence tomography (SD-OCT) and its effect on visual outcomes in eyes
      undergoing silicone oil removal (SOR). METHODS: This was a prospective
      interventional comparative study comprising 42 eyes undergoing SOR with clear
      media. All patients underwent detailed clinical examination and SD-OCT scan of
      fovea pre-operatively and at 30 days and 90 days postoperatively. Patients were
      divided into Group A (n = 21) and Group B (n = 21) depending on presence or
      absence, respectively, of small hyper-reflective spherical bodies in the SSO-FD
      space in preoperative scans. The findings between SD-OCT and best-corrected
      visual acuity were correlated and analyzed. RESULTS: The mean age of patients was
      41.9 years (range, 23-60 years) in Group A and 45.6 years (range, 23-60 years) in
      Group B. Twenty-one eyes showed small hyper-reflective spherical bodies on SD-OCT
      imaging. These were thought to represent emulsified silicone oil globules trapped
      in the potential space created by silicone oil meniscus and foveal pit, which is
      the SSO-FD space. These bodies were absent in all post SOR scans of Group A and
      Group B. Group A had significant visual improvement (p = 0.0001) after SOR with
      clearance of these hyper-reflective bodies as compared to Group B(p = 0.356).
      CONCLUSION: We conclude that these small hyper-reflective spherical bodies in the
      SSO-FD space were most likely emulsified silicone oil globules and correlated
      with significant visual improvement with their clearance after silicone oil
      removal.

PMID- 29018706
TI  - Etiology of orbital fractures at a level I trauma center in a large metropolitan
      city.
AB  - BACKGROUND/PURPOSE: Orbital fractures are a common facial fracture managed by
      multiple surgical specialties. Methods: A retrospective review of the electronic
      medical records of patients (age, 18-85 years) presenting to Northwestern
      Memorial Hospital and Northwestern Medical Faculty Foundation in Chicago, IL, USA
      with International Classification of Diseases, Ninth Revision codes for facial
      fractures or CPT (Current Procedural Terminology) codes for orbital fracture
      repair. RESULTS: A review of the electronic medical records identified 504
      individual incidents of orbital fractures with available imaging for review. The
      most common location for an orbital fracture was a floor fracture (48.0%)
      followed by a medial wall fracture (25.2%). Left-sided orbital fractures were
      statistically significantly more common than right-sided orbital fractures (99%
      confidence interval). Orbital fractures were more prevalent in younger age
      groups. The mean patient age was 39.3 years. The most common cause of all orbital
      fractures was assault followed by falls. However, falls were the most common
      cause of orbital fractures in women and in patients aged 50 years and older.
      Evaluation by an ophthalmologist occurred in 62.8% of orbital fracture patients,
      and evaluation by a team comprising the facial trauma service (Otolaryngology,
      Plastic Surgery, and Oral and Maxillofacial Surgery) occurred in 81.9% of orbital
      fracture patients. CONCLUSION: Assault was the largest cause of all orbital
      fractures, and occurred most commonly in young males. Assaulted patients were
      more likely to have left-sided fractures compared to nonassaulted patients. In
      patients aged 50 years and older, falls were the most common cause of orbital
      fractures.

PMID- 29018707
TI  - Association of refractive error with vision-related quality of life in junior
      high school students.
AB  - BACKGROUND/PURPOSE: To evaluate the relationship between refractive error and
      vision-related quality of life in 16-year-old students in Taiwan. METHODS: A
      cross-sectional study was designed for 16-year junior-high-school students in
      Taiwan. Myopia was defined as a spherical refractive error (SRE) < -0.50 D,
      hyperopia as SRE > +1.0 D, and emmetropia as SRE -0.5-+1.0 D in the better eye.
      Vision-related quality of life was assessed using the Taiwan Chinese version of
      the 25-Item National Eye Institute Visual Functioning Questionnaire. RESULTS: Of
      the 688 participants, 466 (68%) had myopia and 22 (3%) had hyperopia. In logistic
      regression models adjusted for gender, parents' education, family income, and
      parental refractive error, myopia was an independent risk factor of poorer vision
      related quality of life for both near vision (odds ratio 1.73, 95% confidence
      interval 1.22-2.45) and distance vision (odds ratio 3.11, 95% confidence interval
      2.23-4.35). Hyperopia was not associated with near- or distance-vision
      difficulty. CONCLUSION: In this study population, myopia was associated with
      difficulties in near and distance vision compared to emmetropia. Further studies
      are needed to confirm our findings in other populations.

PMID- 29018708
TI  - Spontaneous suprachoroidal hemorrhage: Case report and review of the literature.
AB  - We present the clinical course, management, and final outcome of spontaneous
      suprachoroidal hemorrhage (SSCH) in an age-related macular degeneration (AMD)
      patient-a 64-year-old male receiving antiplatelet therapy who developed SSCH
      during the Valsalva maneuver. In addition to our case study, we discuss the
      results of a systemic review of the literature and reference lists of retrieved
      studies published from January 2001 to December 2013. Among a total of 31
      patients (32 eyes), acute secondary glaucoma was a complication in 87.5% of the
      cases, and over half of the cases (20 eyes, 62.5%) received surgery. Twenty cases
      (64.5%) were characterized by systemic hypertension (HTN), followed by
      cardiovascular or cerebral vascular disease in 17 cases (54.8%). The Valsalva
      maneuver was performed in five cases (16.1%) prior to the episode. Twenty-three
      cases (74.2%) had abnormal hemostasis, including use of anticoagulants or
      thrombolytic agents (18 cases), chronic renal failure (CRF, 5 cases), and blood
      dyscrasia (3 cases). AMD was the most common (17 eyes of 16 patients, 53.1%)
      ocular disease. Visual acuity was classified as hand motion (HM) or worse in 20
      eyes (of 28 eyes, 71.4%) at initial presentation and in 24 eyes (of 30 eyes, 80%)
      upon final examination. Anticoagulated patients with AMD should be informed of
      the risk of intraocular hemorrhage. Medical therapy usually fails in the
      treatment of glaucoma. Surgical intervention provides an option for the purpose
      of pain relief. Even so, the final visual prognosis is usually poor.

PMID- 29018709
TI  - Primary diffuse large B cell lymphoma of the lacrimal sac.
AB  - A 47-year-old man presented with epiphora and a mass around the lacrimal sac in
      his left eye. Imaging studies revealed a favorable diagnosis of sinusitis-related
      mucocele. However, the pathological study of the excised tumor demonstrated a
      diffuse large B cell lymphoma. The patient was consequently referred to the
      oncology department for further management. Malignant lymphomas of the lacrimal
      sac are rare and they can mimic mucoceles. As such, they should be included in
      the list of differential diagnoses for lacrimal sac mass.

PMID- 29018710
TI  - A rare manifestation of neuro-ophthalmic sarcoidosis: A case report.
AB  - PURPOSE: Anterior uveitis is the most common ocular manifestation of sarcoidosis.
      Ocular involvement affects approximately 30-60% of patients with systemic
      sarcoidosis; however, optic disc edema is a rare event. We report a patient who
      presented with a rare case of sarcoidosis with neuro-ophthalmic manifestations.
      CASE REPORT: A 22-year-old man was referred to our clinic with the primary
      complaint of a visual field defect over the temporal side of his right eye of 2
      months duration. He did not have a history of systemic disease. At the first
      ophthalmic examination, the visual acuity, intraocular pressure, and slit lamp
      examination were normal. The fundus examination revealed bilateral optic disc
      edema. He was initially suspected of having a choroidal lesion between the disc
      and fovea of the right eye. To evaluate the possible lesion, the patient
      underwent brain magnetic resonance imaging (MRI), chest radiography, and chest
      computed tomography (CT). There were no abnormalities on the brain MRI, but the
      chest radiographs and CT images revealed bilateral mediastinal and hilar
      lymphadenomegaly. Histopathologic evaluation of an ultrasound-guided lymph node
      biopsy confirmed the diagnosis of sarcoidosis. CONCLUSION: Neuro-ophthalmic
      manifestations of sarcoidosis are rare but may be the only presenting sign of an
      otherwise occult disease. A high clinical suspicion for sarcoidosis and its
      inclusion as a differential diagnosis are key to establishing the diagnosis and
      proper treatment.

PMID- 29018711
TI  - Eradicating trachoma: The experience in Taiwan.

PMID- 29018712
TI  - Trachoma in Asia-A disappearing scourge.
AB  - Trachoma is an ancient blinding eye disease. With improvements in hygiene and
      living conditions and development of targeted strategies by the World Health
      Organization, trachoma is being progressively eliminated. Great progress is being
      seen in Asian countries, many of which are becoming trachoma free.

PMID- 29018713
TI  - Impact of swept source optical coherence tomography on ophthalmology.
AB  - Swept source optical coherence tomography (SS-OCT) was introduced in clinical
      practice in 2012. Because of its deeper penetration and faster acquisition time,
      SS-OCT has the ability to visualize choroid, vitreous, and retinal structures
      behind dense preretinal hemorrhages. Swept source optical coherence tomography
      has positively influenced and hugely contributed to the research of the vitreous
      body. It is the first ophthalmic diagnostic technology to demonstrate the entire
      structure of the posterior precortical vitreous pocket (PPVP) in vivo. The roles
      of the PPVP in physiological posterior vitreous detachment and vitreoretinal
      interface disorders have now been elucidated. The presence of a connecting
      channel between the PPVP and Cloquet's canal suggests that the aqueous humor
      drains into the premacular space. Deeper penetration of SS-OCT has made it
      possible to view the choroid. It also has an important role in central serous
      chorioretinopathy and uveitis. We have also been able to treat Harada disease by
      monitoring the choroidal thickness by SS-OCT.

PMID- 29018714
TI  - Iris-claw versus posterior chamber fixation intraocular lens implantation in
      pediatric traumatic cataract.
AB  - AIM: This study aims to compare visual outcomes and complications of iris-fixated
      (claw) intraocular lens (IFIOL) implantation with those of posterior chamber
      intraocular lens (PCIOL) implantation in children with traumatic cataract.
      SETTINGS AND DESIGN: Retrospective observational clinical audit. MATERIALS AND
      METHODS: A total of 50 pediatric traumatic cataract cases that underwent lens
      removal and IOL implantation (IFIOL or PCIOL) with or without corneal or
      corneoscleral tear repair between January 2009 and December 2013 were analyzed.
      After meeting the eligibility criteria, their pre- and postoperative visual
      outcomes and complication rates were recorded. Data were analyzed descriptively.
      RESULTS: Out of 50 children, IFIOL and PCIOL implantations were performed in one
      eye of each of 25 children. Their mean age was 11 +/- 4 years (range 4-18 years).
      Primary (cataract removal with lens implantation) and secondary (corneal tear
      repair followed by cataract removal with lens implantation) procedures were
      performed in 19 (76%) and six (24%) children in the IFIOL group and in 21 (84%)
      and four (16%) children in the PCIOL group, respectively. There was an
      improvement in best corrected visual acuity postimplantation in both the IFIOL
      and the PCIOL group, and no significant difference in the logarithm of the
      minimum angle of resolution of best corrected visual acuity was observed between
      the two groups over 36 months. Only three eyes in the IFIOL group developed
      complications: one eye developed secondary glaucoma, one disenclavation of IOL
      haptic, and one cystoid macular edema. CONCLUSION: Both IFIOL and PCIOL
      implantations have good visual outcomes and minimal postoperative complications;
      therefore, IFIOL can be used as an alternative to PCIOL in children with
      traumatic cataract with inadequate capsular support.

PMID- 29018715
TI  - Reducing intraocular-pressure spike after intravitreal-bevacizumab injection with
      ocular decompression using a sterile cotton swab soaked in proparacaine 0.5%: A
      quasi-experimental study.
AB  - BACKGROUND/PURPOSE: The study was conducted to determine the effect of
      preinjection ocular decompression by a cotton swab soaked in local anesthetic on
      the immediate postinjection rise in intraocular pressure (IOP) after intravitreal
      bevacizumab (IVB). METHODS: A nonrandomized, quasi-experimental interventional
      study was conducted at Al-Shifa Trust Eye Hospital, Pakistan, from August 1, 2013
      to July 31, 2014. One hundred (n = 100) patients receiving 0.05-mL IVB injection
      for the first time were assigned to two preinjection anesthetic methods: one with
      ocular decompression using a sterile cotton swab soaked in proparacaine 0.5%, and
      the other without ocular decompression using proparacaine 0.5% eyedrops. The IOP
      was recorded in the eye receiving IVB at three time intervals: Time 1
      (preinjection), Time 2 (immediately after injection), and Time 3 (30 minutes
      after injection). RESULTS: There was a significant difference in the mean IOP
      change (between Time 1 and Time 2) for the group injected with ocular
      decompression [M = 1.00, standard deviation (SD) = 1.47] and the group injected
      without ocular decompression (M = 5.00, SD = 2.38; t (68) = 9.761, p < 0.001).
      There was also a significant difference in the mean IOP change (between Time 1
      and Time 3) for the group injected with ocular decompression (M = 0.428, SD =
      1.58) and the group injected without ocular decompression (M = 4.318, SD = 3.34;
      t (58) = 7.111, p < 0.001). CONCLUSION: Patients receiving IVB injections with
      ocular-decompression soaking in proparacaine 0.5% experience significantly lower
      postinjection IOP spike, and that too for a considerably shorter duration as
      compared to those receiving IVB without ocular decompression.

PMID- 29018716
TI  - Retinoblastoma in Mongolia: Clinical characteristics and survival from 1987 to
      2014.
AB  - BACKGROUND/PURPOSE: This study aims to describe the clinical characteristics and
      treatment outcome of retinoblastoma in Mongolian children. METHODS: Data of all
      children diagnosed with retinoblastoma at the National Center for Maternal and
      Child Health of Mongolia from 1987 to January 2014 were reviewed retrospectively.
      The ICRB classification was used. Survival characteristics of the cohort were
      analyzed. RESULTS: Retinoblastoma was diagnosed in 79 eyes of 64 cases during the
      study period. Median age of diagnosis was 24.5 +/- 15.8 months. There were no
      differences in sex ratio, and 15 cases (23%) were bilateral. Forty-three (67%)
      patients were from rural areas. The more frequent clinical presentations were
      leukocoria in 50 (78%) patients, strabismus in 24 (38%) patients, and glaucoma in
      21 (33%) patients. Sixty-one (95%) patients were diagnosed with Classification D
      or worse when presented to us. Due to late diagnosis in the majority of cases,
      unilateral and bilateral enucleations were performed in 48 (61%) eyes and 24
      (30%) eyes, respectively; exenteration was done in three (4%) eyes. Fifty-two
      (81%) patients received chemotherapy and 13 (8.3%) patients underwent external
      beam radiation after enucleation. At the time of last follow-up, 52 (81%)
      patients were alive, five (8%) patients were dead, and seven (11%) patients had
      lost to follow-up or unknown vital status. The mean follow-up period was 121.5
      months (range, 12-360 months). In five cases with immunohistochemistry analysis
      in the eye specimen, neuron-specific enolase-, Ki-67 protein-, and B-cell
      lymphoma 2-positive cells were found in all five (100%) cases and Rb protein was
      detected in three (60%) cases. CONCLUSION: Retinoblastoma in Mongolia is
      frequently diagnosed at late stages and has a poor outcome. These data show the
      importance of early pediatric eye examinations and better treatment of retino
      blastoma in children younger than 3 years in Mongolia.

PMID- 29018717
TI  - Clinical characters and treatments of retinal vasoproliferative tumors.
AB  - Retinal vasoproliferative tumors (VPT) are uncommon benign vascular tumors. They
      mostly occur in healthy patients, but may be associated with other chorioretinal
      diseases. Here we report four patients with VPT at a referral center from 2006 to
      2015. Three patients denied any past history and one had a history of retinal
      detachment surgery. VPT-related complications included epiretinal membrane (ERM)
      (n = 2), cystoids macular edema (n = 1), and lamellar hole combined with dense
      cataract, rigid anterior capsule and vitreous opacity (n = 1). Treatments for VPT
      and comorbidities included vitrectomy (VT) and membrane peeling with tumor
      resection (n = 2), a combined treatment of photodynamic therapy (PDT) and
      intravitreal injection (IVI) of anti-vascular endothelial growth factor (anti
      VEGF) (n = 2). Tumor shrinkage was achieved in both patients treated with PDT and
      IVI of anti-VEGF injection. The other two patients with ERM were successfully
      treated with VT and tumor resection. Visual acuity improved at least two lines in
      three patients, and one patient had decreased vision due to cataract formation
      after VT. Pathology of the resected tumor in one case revealed massive gliosis
      with positive stain of vascular endothelial cells and glial fibrillary acidic
      protein stain. Yet the peeled membrane was acellular. Possible beneficial
      treatments for VPT and comorbidities include PDT combined with IVI of anti-VEGF,
      or VT and membrane peeling with tumor resection.

PMID- 29018718
TI  - Ipsilateral rotational autokeratoplasty for central corneal scar: An alternative
      to penetrating keratoplasty.
AB  - A 49-year-old woman was referred to our clinic for penetrating keratoplasty. A
      central corneal scar involving the visual axis with high irregular astigmatism up
      to 15.8 D was noted. Because the scar was located mostly in the central cornea,
      ipsilateral rotational autokeratoplasty was suggested and performed. An 8.5-mm
      punch was used to trephine the cornea eccentrically and superiorly intentionally.
      The trephined corneal button was then rotated 150 degrees  to relocate the scar
      to the temporal upper part of the cornea. The graft was soon clear with a normal
      curvature centrally. The astigmatism was -0.5 D, the visual acuity was 20/40, and
      the endothelial cell loss was 2.66% 2 years after the operation. A rotational
      autograft carries no risk of immunological complications such as rejection
      associated with allografts and has lower endothelial cell loss rate. It can be an
      effective alternative to standard penetrating keratoplasty for some patients with
      central corneal scars.

PMID- 29018719
TI  - Needle decompression in a patient with vision-threatening orbital emphysema.
AB  - Orbital emphysema is a condition resulting from trapping of air in loose
      subcutaneous or orbital tissues from the paranasal sinuses. This condition
      commonly seen in patients with a history of periorbital trauma or surgery,
      especially following sneezing or nose blowing. It usually has a benign and self
      limited course. However, the entrapped orbital air can cause a substantial
      increase in pressure with restricted ocular motility or vascular compromise and
      become severe enough to cause visual impairment. We herein present the case of a
      patient who developed severe orbital emphysema after blunt trauma followed by
      sneezing and was successfully treated with needle decompression of intraorbital
      air. Emergency needle decompression resulted in an improvement in vision and
      intraocular pressure.

PMID- 29018720
TI  - Deep vein thrombosis due to continuous prone positioning after retinal detachment
      surgery.
AB  - In March 2014, a 56-year-old woman without previous underlying disease underwent
      encircling scleral buckling, 20-gauge pars plana vitrectomy, cryotherapy around a
      retinal tear, and gas-fluid exchange with 15% perfluoropropane flush for upper
      rhegmatogenous retinal detachment of the left eye. However, she developed
      progressive left leg swelling, pain, warmth, and redness, associated with
      difficulty in elevating her left leg after continuously maintaining a prone head
      position when either lying down or sitting for 2 days. When she arrived at the
      emergency room, she had an elevated D-dimer level. After undergoing Doppler
      ultrasound imaging, she was diagnosed as having deep vein thrombosis of the left
      leg. She received anticoagulation therapy with enoxaparin and warfarin
      overlapping for 7 days. The edema, pain, and paresthesia of her left leg were
      relieved. However, because of the risk of bleeding with anti-coagulation drug
      usage, the patient needed to be monitored for 6 months. Prone positioning for gas
      tamponade is important for anatomic and functional success in retinal detachment
      surgery; however, timely walking and rest between periods of continuous prone
      positioning should be encouraged to prevent deep vein thrombosis and other
      impaired circulation-related complications.

PMID- 29018721
TI  - Methicillin-resistant Staphylococcus aureus buckle infection complicated by
      endophthalmitis and presumed choroidal abscess in a patient with ulcerative
      colitis.
AB  - This patient presented with excessive pain, lid swelling, erythema, heat and
      limitations of extraocular movement (OD) nine days after a scleral buckle (SB)
      and pneumopexy surgery. Complicated buckle infection with endophthalmitis was
      impressed. Bacterial culture yielded methicillin-resistant Staphylococcus aureus.
      A choroidal abscess was identified 1 week after the episode. Complete visual
      recovery from hand motion to 20/30 (OD) was achieved with buckle removal,
      subconjunctival and intravitreal antibiotics. Endophthalmitis and choroidal
      abscess formation after SB surgery is extremely rare. Host factors including
      ulcerative colitis may play a role in causing the severe buckle infection of this
      patient.

PMID- 29018722
TI  - This issue at a glance.

PMID- 29018723
TI  - Restrictive problems related to strabismus surgery.
AB  - Strabismus surgery may be responsible for some restrictions in ocular motility
      that may cause new problems after surgery. Most of the time these restrictions
      present as a complex motility problem after surgery that requires further
      treatment. There may be various reasons that cause motility restriction following
      strabismus surgery. Those are excessive shortening or inadvertent capture of
      extraocular muscles, transposition procedures and, the most challenging problem,
      postoperative scar tissue-adhesion formation. In this review the potential
      reasons for postoperative restrictive problems, preventive measures and finally
      the treatment options for such problems are overviewed.

PMID- 29018724
TI  - Cold medicine-related Stevens-Johnson syndrome/toxic epidermal necrolysis with
      severe ocular complications-phenotypes and genetic predispositions.
AB  - Stevens-Johnson syndrome (SJS) is an acute inflammatory vesiculobullous reaction
      of the skin and mucosa, such as the ocular surface, oral cavity, and genitals. In
      patients with extensive skin detachment and a poor prognosis, the condition is
      called toxic epidermal necrolysis (TEN). Severe ocular complications (SOCs)
      appear in some-but not all-SJS/TEN patients who are diagnosed by dermatologists,
      and cold medicines including multi-ingredient cold medications and nonsteroidal
      anti-inflammatory drugs are the main causative drugs particularly for SJS/TEN
      with SOCs and all SJS and TEN. In this review, we focus on the genetic
      predisposition of cold medicine-related SJS/TEN (CM-SJS/TEN) with SOCs. CM
      SJS/TEN with SOCs was strongly associated with HLA-A*02:06 and significantly
      associated with HLA-B*44:03 in Japanese individuals, significantly associated
      with HLA-B*44:03 in Indian and Brazilian individuals, and associated with HLA
      A*02:06 in Korean individuals. In the first genome-wide association study (GWAS),
      we found an association between the prostaglandin E receptor 3 (PTGER3) gene and
      SJS/TEN with SOCs. In this study, we focused on CM-SJS/TEN with SOCs and found
      that the association of CM-SJS/TEN with SOCs became stronger than all SJS/TEN
      with SOCs. In the second GWAS, we found an association between the IKZF1 gene and
      CM-SJS/TEN with SOCs not only in Japanese, but also in Korean and Indian
      populations. Moreover, we found that TSHZ2 gene single nucleotide polymorphisms
      (SNPs) also showed especially low p values in the Japanese population; however,
      this association was not found in the Korean population. Furthermore, we
      investigated the interaction between susceptibility genes, and found
      multiplicative interactions of HLA-A*02:06 and TLR3 SNPs and additive
      interactions of HLA-A*02:06 and PTGER3 SNPs.

PMID- 29018725
TI  - Challenges in the management of glaucoma in developing countries.
AB  - Glaucoma is the most common optic neuropathy characterized by normal to raised
      intraocular pressure (IOP), visual field defects, loss of retinal nerve fiber
      layer, thinning of the neuroretinal rim, and cupping of the optic disc. IOP
      reduction by medical, laser, or surgical therapies remains the only clinically
      proven treatment of glaucoma. The challenges in glaucoma management are diverse.
      They include early detection and diagnosis, setting of appropriate target IOP,
      choice of treatment, monitoring of quality of life and sight, and compliance with
      the treatment. Early diagnosis can be made by assessing optic nerve structure
      using imaging devices and optic nerve function through perimetry. Reducing IOP
      and controlling its fluctuations are considered to be the most important factors
      in limiting progression of glaucoma. Selection of the best suitable therapy out
      of medical, surgical, or laser treatment options is yet another management
      challenge. Patients suffering from glaucoma experience poor quality of life owing
      to the diagnosis itself, functional visual loss, inconvenience and cost of
      treatment, and side effects of treatment. All these factors lead to poor
      compliance, adherence, and persistence to treatment, and further progression of
      the disease. It is, therefore, important that ophthalmologists keep all the
      aforementioned factors in mind when managing patients with glaucoma.

PMID- 29018726
TI  - Colored corn starch dust explosion-related ocular injuries at a Taiwan water
      park: A preliminary report from a single medical center.
AB  - PURPOSE: To elucidate the manifestations of ocular injuries in the colored corn
      starch dust explosion at a Taiwan water park. METHODS: This is a retrospective,
      non-comparative, consecutive-interventional case series. Fifty explosion-injury
      patients on 27 June 2015 treated at Chang-Gung Memorial Hospital, Linkou, were
      included. Thorough ophthalmic examinations were based on emergent triage and
      consecutive ophthalmological consultations. Multiple ocular and systemic
      parameters were assessed. RESULTS: Of the 100 eyes in the 50 cases reviewed, 22
      cases were male and 28 cases were female. The mean age was 22.08 +/- 4.64 years,
      and the mean burn total body surface area (TBSA) of patients was 45.92 +/-
      20.30%. Of the 50 patients, 20 had Grade 1 ocular burns, and the others were
      without ocular involvement. Two of the 20 cases that presented Grade 1 ocular
      burns died within 1 month due to other systemic complications. The most common
      ocular manifestations among those with ocular injuries included periocular
      swelling (75%), followed by conjunctival chemosis (65%), conjunctival hyperemia
      (50%), singed eyelashes (20%), cornea epithelial defects (10%), and punctate
      keratopathy (5%). It is worth mentioning that one patient developed herpes
      simplex keratitis due to stress 3 weeks after being burned. Half of the 50
      patients had facial burns. Specifically, the patients with a greater TBSA
      presented more significant ocular-burn manifestations than those patients with
      lower TBSA. CONCLUSION: Prompt ophthalmologic consultations are particularly
      necessary for mass burn-casualty patients with facial burns, inhalation injuries,
      and greater TBSA. The inspection and control of all ignition sources and the
      manipulation of dust with low concentrations and in an open space are crucial
      factors to prevent future dust explosions.

PMID- 29018727
TI  - Comparative study of changes of corneal curvatures and uncorrected distance
      visual acuity prior to and after corneal collagen crosslinking: 1-year results.
AB  - BACKGROUND/PURPOSE: Keratoconus is the most common primary corneal ectatic
      disease and has considerable importance in public health. Corneal collagen
      crosslinking (CXL) is a procedure to mitigate progression of keratoconus and
      reduce demand for corneal transplantation. The aim of this study was to evaluate
      the effect of CXL on corneal topographic and uncorrected distance visual acuity
      (UDVA) by Oculus Pentacam in the 15-30-year-old population. METHODS: In this
      descriptive-analytic study, we enrolled 38 eyes of 27 patients suffering from
      progressive keratoconus who were candidates for CXL. UDVA and the anterior and
      posterior corneal curvatures assessed prior to and 12 months after CXL. Data were
      analyzed by the paired t test and p < 0.05 was considered significant. RESULTS:
      One year after the CXL, mean UDVA significantly improved 0.1 +/- 0.25 logarithm
      of the minimal angle of resolution (p = 0.012). Changes for steep keratometry
      values, flat keratometry, and mean keratometry on the anterior corneal surface
      were statistically significant (all p < 0.005). However, the difference observed
      in maximum keratometry and astigmatism was not significant (p = 0.421 and p =
      0.745, respectively). After 12 months, all four keratometry values on the
      posterior corneal surface had increased significantly (p < 0.005), while no
      significant change observed in astigmatism (p = 0.303). CONCLUSION: Corneal
      collagen crosslinking has been revealed as an effective and minimally invasive
      intervention for the treatment of progressive keratoconus that can improve UDVA.

PMID- 29018728
TI  - Effect of potassium channel openers in acute and chronic models of glaucoma.
AB  - PURPOSE: Glaucoma is characterized by increased intraocular pressure (IOP). The
      effect of nicorandil and pinacidil on IOP in experimentally induced acute and
      chronic models of glaucoma and the mechanism of action involved were studied.
      METHODS: New Zealand white rabbits were used for the study. After the measurement
      of IOP, nicorandil (1%), pinacidil (1%), and pilocarpine as standard (1%) were
      instilled topically into the left eye. The other eye served as control. Dextrose
      (5%) was used to induce acute glaucoma. IOP changes were recorded every 15
      minutes until the pressure became normal. Freshly prepared alpha-chymotrypsin
      solution was introduced in the posterior chamber to induce chronic glaucoma.
      Rabbits with ocular hypertension were selected for the study. Similar drug
      solutions were used to study the effect on IOP. Glibenclamide, pilocarpine, and
      indomethacin (1%) were used to study the mechanism of action of both drugs. The
      IOPs were measured just prior to drug instillation and at suitable time intervals
      using a tonometer. RESULTS: Pretreatment with topical nicorandil and pinacidil
      significantly lowered the rise in IOP in the acute model. Nicorandil and
      pinacidil initially caused rise in IOP for 15-30 minutes in chronic glaucoma.
      This was followed by reduction in IOP. Pretreatment with indomethacin and
      pilocarpine did not modify the effect of nicorandil and pinacidil on IOP.
      Pretreatment with glibenclamide blocked IOP from the lowering effect of
      nicorandil and pinacidil. CONCLUSION: The oculohypotensive effect shown by these
      drugs appears to be attributable to enhancement of the aqueous humor outflow.
      This effect is perhaps mediated through potassium channels.

PMID- 29018730
TI  - 26-G needle-assisted sutureless glueless intrascleral haptic fixation for
      secondary ciliary sulcus implantation of three-piece polymethylmethacrylate
      intraocular lens during penetrating keratoplasty.
AB  - After tenotomy adjoining 3 o'clock and 9 o'clock limbus, 3-mm-wide partial
      thickness scleral tunnels are created at these two diametrically opposite points
      3 mm from the limbus such that they reach up to a distance of 1.5 mm from the
      limbus. Two ab externo sclerotomies are created using 26-G needles on the bed of
      these partial-thickness scleral tunnels. Precaution is taken to ensure that the
      positions of the sclerotomies are diagonally opposite each other. A scleral niche
      is made using a 26-G needle to accommodate the intraocular lens (IOL) haptic
      later. A 7.5-mm trephine is used to excise the corneal button, and anterior
      vitrectomy is performed. The haptic of a three-piece polymethylmethacrylate IOL
      is docked in a bent 26-G needle. It is then pulled out under the partial
      thickness scleral tunnel and placed securely in the scleral niche opposite to the
      haptic. An 8-mm donor corneal button is sutured in place using 16 equidistantly
      placed 10-0 nylon interrupted sutures.

PMID- 29018729
TI  - Clinical characteristics and visual outcome of macular hemorrhage in pathological
      myopia with or without choroidal neovascularization.
AB  - BACKGROUND/PURPOSE: This study aims to evaluate the clinical characteristics and
      visual outcome of macular hemorrhage in pathological myopia with or without
      choroidal neovascularization. METHODS: We conducted a retrospective study of 55
      patients with macular coin hemorrhage who were followed for at least 3 months
      from January 1997 to December 2013 at Shin Kong Wu Ho-Su Memorial Hospital
      (Taipei, Taiwan). All patients were evaluated using fluorescein angiography and
      optical coherence tomography for the detection of choroidal neovascularization
      (CNV). We also recorded clinical characteristics such as age, sex, refractory
      error, and myopic fundus, to determine the relationship between CNV and non-CNV
      associated macular hemorrhage. RESULTS: A total of 55 patients (30 females,
      54.55%) were reviewed. The mean age was 39.7 years old. The CNV group was found
      to be significantly older than the non-CNV group (p < 0.05), and there was no
      significant difference between sex, visual acuity myopic severity, and the
      prevalence of fundus findings between CNV and non-CNV groups. Twenty one patients
      (38.18%) were found to have CNV and were all treated with intravitreal
      antivascular endothelial growth factor (VEGF). The other 34 patients without CNV
      were not treated. In both groups, the visual acuity significantly improved (anti
      VEGF treated, CNV associated group, 0.7 to 0.39, p = 0.002, and untreated, non
      CNV associated group, 0.56 to 0.34, p = 0.0018, respectively). CONCLUSION: Age
      significantly correlated to the CNV formation in high myopia with macular
      hemorrhage. Favorable visual outcomes were found in pathological myopic macular
      hemorrhage either in the anti-VEGF treated, CNV associated group or in the
      untreated, non-CNV associated group.

PMID- 29018732
TI  - Bilateral retinal pigment epithelial rips in hypertensive choroidopathy.
AB  - Severe systemic hypertension can cause significant damage to the eye. Although
      hypertensive retinopathy is a well-known complication, hypertensive optic
      neuropathy and hypertensive choroidopathy are much less common. The aim of this
      article is to report an unusual case of hypertensive choroidopathy with bullous
      exudative retinal detachments in both eyes. The retinal detachments spontaneously
      resolved after blood pressure was controlled. However, multiple large retinal
      pigment epithelial (RPE) rips were found in both eyes. These RPE rips may be
      related to severe choroidal ischemia, and their locations may be compatible with
      the watershed zones of the choroidal perfusions.

PMID- 29018731
TI  - Rapid regression of cystoid macular edema associated with cytomegalovirus
      retinitis in adult acute myeloid leukemia by intravitreal methotrexate combined
      with oral valganciclovir: A case report with comparison of binocular outcome.
AB  - Cytomegalovirus (CMV) retinitis is a late complication of organ and hematopoietic
      stem cell transplant, the risk of which depends on the degree of
      immunosuppression. With the institution of preemptive ganciclovir therapy early
      after transplant, most patients survive episodes of life-threatening CMV
      infection during the early months (usually the first 3 months) after transplant
      and hence late onset of CMV disease, such as CMV retinitis, is being recognized
      more frequently. Direct involvement of the macula or optic head remains the
      leading cause of visual loss in patients with CMV retinitis, but there are few
      studies investigating the management of this condition. Herein, we present the
      case of 28-year-old man who had acute myeloid leukemia and developed CMV
      retinitis with bilateral cystoid macular edema and optic swelling in the right
      eye 6 months after bone marrow transplant. He received treatment with
      intravitreal methotrexate in the right eye in combination with oral
      valganciclovir. Visual acuity improved 1 month after four weekly injections of
      intravitreal methotrexate 400 ug/0.1 mL. Resolved disc swelling and regression of
      macular edema were also observed. By comparing binocular outcome, we present our
      findings and discuss the possible efficacy and safety of this treatment with
      respect to regression of anatomical damage and improvement in visual acuity.

PMID- 29018734
TI  - Optimizing surgical treatments in rhegmatogenous retinal detachment.

PMID- 29018733
TI  - Candida parapsilosis keratitis treated successfully with topical and oral
      fluconazole.
AB  - A 73-year-old male patient presented with ocular pain, redness, and blurred
      vision in the left eye, which had been ongoing for more than 2 months. An oval
      shaped paracentral corneal ulcer with stromal infiltration and a mild anterior
      chamber reaction were found. Despite treatment with empiric antibiotics, the
      lesion progressed and corneal thinning in the middle area was noted. The culture
      yielded Candida parapsilosis. We therefore prescribed topical 0.2% fluconazole
      (FCZ) in combination with oral FCZ as an antifungal treatment, following which
      the stromal infiltration gradually subsided. Complete epithelial-ization was
      noted on the 8th day after initiating FCZ therapy. There was no recurrent disease
      in the subsequent 2 years. Our case demonstrates that topical FCZ 0.2% in
      combination with oral FCZ can successfully treat C. parapsilosis keratitis and
      result in a good visual outcome.

PMID- 29018735
TI  - Primary retinal detachment: A review of the development of techniques for repair
      in the past 80 years.
AB  - BACKGROUND/PURPOSE: The evolution of present surgical techniques for reattaching
      a primary retinal detachment will be reviewed starting from 1929, and the present
      techniques analyzed in regard to their morbidity, reoperation, and long-term
      visual function. METHODS: Literature of retinal detachment operations during the
      past 80 years is reviewed, of which the author has first-hand experience during
      the past 40 years. There had been a change from surgery of the entire detachment
      to a surgery limited to the retinal break and a change from extraocular to
      intraocular surgery. RESULTS: The four major operations for repair of a primary
      retinal detachment in use at the beginning of the 21st century, have still one
      thing in common for sustained reattachment: to find and close the break that
      caused the primary retinal detachment and that would cause a redetachment, if not
      sealed completely. This is independent of whether the surgery is limited to the
      break or extends over the entire detachment and the same is true whether the
      surgery is performed as an extraocular or intraocular procedure. CONCLUSION: To
      find and close sufficiently the break in a primary retinal detachment has
      accompanied the efforts of retinal detachment surgeons during the past 80 years.
      This is still the premise for sustained reattachment. However, today four
      postulates have to be fulfilled: (1) retinal reattachment with the first
      operation; (2) the procedure should have a minimum of morbidity; (3) the
      procedure should not harbor secondary complications jeopardizing regained visual
      acuity; and (4) the procedure should be performed on a small budget with local
      anesthesia.

PMID- 29018737
TI  - Evidence-based medicine in glaucoma surgery.
AB  - Evidence-based medicine (EBM) is a tool and guide for performing effective
      medical treatment. Here, as an example, EBM was applied to determine which
      between trabeculectomy and Baerveldt implant surgery would be more effective in a
      patient with a history of open-angle glaucoma. First, the author asked answerable
      clinical questions. Second, evidence using general search engines, such as the
      Cochrane Library or MEDLINE database, was collected. It was found that the Tube
      Versus Trabeculectomy (TVT) Study was a landmark study in determining optimum
      glaucoma surgical procedure. Third, the study's level of evidence was carefully
      examined. As the TVT Study was a prospective, randomized multicenter control
      study, its level of evidence was high. Fourth, the evidence to actual clinical
      decisions was applied, calculating the magnitude of the treatment effect using
      the results of the TVT Study. The event (surgical failure) rate in the control
      (trabeculectomy) and experimental (tube implant) groups (control event rate and
      experimental event rate, respectively) was obtained and the absolute risk
      reduction (ARR) was calculated by subtracting the experimental event rate from
      the control event rate. The inverse of ARR is the number needed to treat (NNT),
      which is the number of patients who must be treated to prevent a bad outcome.
      Using this method, it is possible to calculate the absolute risk (adverse event)
      increase (ARI) and the number needed to harm one more patient (NNH = 1/ARI). The
      balance of NNT and NNH is called the "likelihood of being helped and harmed." The
      practice of EBM integrates clinical expertise of individuals with the best
      available external clinical evidence from systematic research.

PMID- 29018736
TI  - Recent progress in the diagnosis and treatment of primary vitreoretinal lymphoma.
AB  - Primary vitreoretinal lymphoma (PVRL) was previously termed primary intraocular
      lymphoma. PVRL is a potentially fatal intraocular malignancy, and 65-90% of PVRL
      cases eventually involve the central nervous system (CNS). The incidence of PVRL
      has been rising in both immunocompromised and immuno-competent populations
      worldwide. PVRL frequently masquerades as chronic uveitis. Advanced auxiliary
      examinations, such as optical coherence tomography and fundus autofluorescence
      have been applied in the diagnosis of PVRL. Histology and immunohistochemistry in
      combination with molecular tests and interleukin-10 analysis have been
      demonstrated as reliable in diagnosing PVRL. Despite early initiation of
      treatment, mortality is high with PVRL associated with CNS involvement and
      relapses are common. The use of systemic chemotherapy has not been proven to
      prevent CNS involvement; however, local therapies including intravitreal
      injections of methotrexate and/or rituximab and low-dose radiotherapy to the eye,
      has shown to be extremely effective in controlling intraocular lymphoma with
      encouraging results.

PMID- 29018738
TI  - Controversies in the vascular theory of glaucomatous optic nerve degeneration.
AB  - An understanding of the pathogenesis of glaucoma is one of the foundations in
      glaucoma management. A number of theories have been presented to explain
      glaucomatous neural degeneration. The vascular theory attempts to explain the
      causation of glaucoma on the basis of vasogenic factors and altered he-modynamics
      in the body; however, this theory remains controversial. There are proponents for
      and against the role played by vascular factors in the development of
      glaucomatous optic nerve degeneration. This review aims to analyze the various
      studies performed to provide evidence for and against the vascular theory of
      glaucoma. It also affirms the need to undertake further studies regarding the
      path-ogenesis of glaucoma and integrate them into our management strategies. The
      literature search for this systemic analysis was performed using search engines,
      such as PubMed, The Virtual Library of the Ministry of Health Malaysia, Google
      Scholar, and ClinicalKey.

PMID- 29018740
TI  - Simple dacryops: Do we really need imaging?

PMID- 29018741
TI  - Vitrectomy for macular hole following Nd:YAG laser injury.
AB  - The Q-switched Nd:YAG laser can cause significant ocular injury, because it can
      emit an invisible and powerful load of energy in a short period of time. One of
      these injuries is macular hole formation. We report the case of a 21-year-old
      woman who presented with acute floaters in her left eye after exposure to a Q
      switched Nd:YAG laser. Her initial best-corrected visual acuity (BCVA) in the
      left eye was 20/80. Examination demonstrated an acute vitreous hemorrhage, and
      spectral-domain optical coherence tomography (SD-OCT) confirmed a full-thickness
      macular hole (FTMH). Four months after her injury, her BCVA deteriorated to
      20/400, and she underwent vitrectomy, internal limiting membrane peeling, and gas
      injection. Three weeks following the procedure, her FTMH was closed, however, her
      BCVA remained 20/150. At her last office visit, 19 months after the surgery, the
      examination was unchanged. There are few reports of vitrectomy to close an FTMH
      after Nd:YAG laser exposure, and the factors that contribute to visual recovery
      remain unclear. The aim of this case report is to emphasize the importance of
      early diagnosis and surgical repair, and to review the literature and surgical
      outcomes of cases of Nd:YAG laser-induced macular holes. Imaging with SD-OCT was
      essential in evaluating the visual outcome, as it was dependent on the degree of
      photoreceptor and retinal pigment epithelium injury.

PMID- 29018739
TI  - The distribution of near point of convergence, near horizontal heterophoria, and
      near vergence among myopic children in South Korea.
AB  - BACKGROUND/PURPOSE: To assess the distribution of near point of convergence
      (NPC), near heterophoria, and near vergence among myopic school children in South
      Korea. METHODS: One hundred and thirty-six elementary school children, aged 8-13
      years, were each given a thorough eye examination including binocular vision
      testing, NPC using standard push-up technique, horizontal heterophoria
      measurement by Von Graefe, distance, and near negative and positive vergence with
      a phoropter and phoropter replacement card. RESULTS: NPC break and recovery
      points were highest in the age 9 years group, but the mean values of NPC were
      within the normal range. Of 136 individuals, 52 presented with esophoria, 53
      presented with 0 -6-Delta exophoria, and 31 presented with >=7-Delta exophoria.
      In the younger age groups (8 years and 10 years) 0-6-Delta exophoria was
      prevalent, whereas in the older age groups (11 years, 12 years, and 13 years)
      esophoria was prevalent. Near positive fusional vergence (break and recovery
      point) presented with statistically significant correlations with the
      participants' ages. Esophoria showed higher correlations with high myopia (8.00
      +/- 0.000) rather than with low myopia (3.36 +/- 2.499) or medium myopia (3.42 +/
      2.149). The mean value of 0-6Delta exophoria was highest in medium myopia (4.04
      +/- 1.517), and of >=7-Delta exophoria was the highest in high myopia (12.66 +/-
      1.154). CONCLUSION: There were no statistically significant correlations between
      the school childrens' ages and NPC, near horizontal heterophoria, and near
      fusional vergence, except near positive fusional vergence. Also, unlike many
      studies, myopic magnitude did not present a significant correlation with near
      phoria and fusional vergence.

PMID- 29018742
TI  - Novel technique for removal of persistent subretinal fluid following nondrain
      retinal detachment surgery.
AB  - This manuscript describes a case of successful reattachment of a macular-off
      retinal detachment following optical coherence tomography-guided internal
      drainage of retained subretinal fluid following a nondrain method. To date, there
      has not been any documented treatment option for this common phenomenon. This
      novel technique describes a method to remove such fluid and successfully appose
      the retina to the retinal pigment epithelial layer.

PMID- 29018743
TI  - Contact dermatitis on the lower eyelid related to tick infestation: A case report
      in Taiwan.
AB  - Tick bite on the lower eyelid is a rare condition. We reported a case of contact
      dermatitis on the lower eyelid related to the tick infestation. Ticks are vectors
      for disease transmission. Symptoms and treatments for tick-borne diseases were
      reviewed.

PMID- 29018744
TI  - Ocular syphilis masquerading as bilateral peripheral ulcerative keratitis.
AB  - Ocular syphilis has varied manifestations in the eye. Peripheral ulcerative
      keratitis (PUK) is a crescent-shaped ulcer involving the peripheral cornea and
      associated with thinning. PUK is caused by both autoimmune and infectious
      diseases, such as rheumatoid arthritis, tuberculosis, and herpes. Here, we report
      a rare case of bilateral PUK caused by syphilis. A 55-year-old man presented with
      recurrent pain and redness in both eyes for 2 months. The cornea of both eyes had
      bilateral peripheral crescent-shaped ulcers suggestive of PUK. The patient was
      started on topical steroids elsewhere, but the lesion was not showing any signs
      of healing. A series of investigations were performed, with positive venereal
      disease research laboratory and fluorescent treponemal antibody absorption tests.
      The patient was then started on systemic penicillin, as well as topical steroids.
      The response to the treatment was good and the ulcer began to heal. PUK as the
      presenting feature of acquired syphilis is a rare scenario. Such infective causes
      should be managed with systemic antimicrobials for optimal outcomes.

PMID- 29018746
TI  - An innovative era of pediatric ophthalmology and strabismus.

PMID- 29018745
TI  - Treacher Collins syndrome: A case report and review of ophthalmic features.
AB  - Treacher Collins syndrome is a congenital disorder with bilaterally symmetric
      anomalies of the structures developing from the first and second branchial
      arches. The ocular and orbital features are an obligatory component for the
      diagnosis. We presented a case of typical, complete syndrome and also reviewed
      the varied ophthalmological manifestations of the disease in the literature.
      Antimongoloid slanting of palpebral fissures and lower lid colobomas are constant
      features of the syndrome. However, varied ocular and lacrimal drainage anomalies
      are also associated. TCS is a syndrome with multiple ocular and orbital features,
      a knowledge of which will help in the diagnosis of incomplete forms of the
      syndrome.

PMID- 29018747
TI  - Pearls and pitfalls in the management of Duane syndrome.
AB  - Duane syndrome (DS) is a common form of congenital cranial dysinnervation
      disorders. The ocular motility pattern lies in a wide clinical spectrum, and the
      choice of treatment must be individualized depending on the severity of the
      clinical findings. There is no perfect method of treatment and no real "cure" in
      DS. In this paper, the aim is to give some guidelines to the reader for selection
      of the most appropriate treatment method for the patient.

PMID- 29018748
TI  - Historical review of inferior oblique muscle surgery.
AB  - Surgery on inferior oblique muscle has a long history and various surgical
      techniques have been developed. The historical review of the surgery starting in
      1840's to date is performed. The surgical effectiveness between simple myectomy
      and recession is still controversial.

PMID- 29018749
TI  - The diagnostic challenge of evaluating papilledema in the pediatric patient.
AB  - Pseudopapilledema is a fairly common finding in ophthalmic practice, and in many
      cases, the diagnosis is straightforward. However, an accurate diagnosis can
      challenge the most seasoned clinicians, and missing true papilledema can result
      in life-threatening or vision-threatening consequences. In this review, we
      describe the clinical findings and a diagnostic algorithm to distinguish
      pseudopapilledema and papilledema in the pediatric patients. We also describe the
      clinical evaluation once a diagnosis of papilledema has been established.

PMID- 29018750
TI  - Management of diplopia with visual-field defects.
AB  - PURPOSE: The management of diplopia can be challenging in patients with a
      concurrent visual-field (VF) defect. We conducted a retrospective chart review to
      analyze and compare treatment outcomes for different types of VF defects.
      METHODS: A retrospective chart review. RESULTS: Seven patients with diplopia and
      VF defects were identified during the study. Four had bitemporal hemianopia, one
      had homonymous hemianopia, and two had a constricted central VF. A favorable or
      satisfactory outcome was achieved in all but two patients with bitemporal
      hemianopia. CONCLUSIONS: The hemifield-slide diplopia may develop in patients
      with bitemporal hemianopia or heteronymous altitudinal visual defects. Sensory
      abnormalities usually persist, even after elimination of ocular misalignment.

PMID- 29018751
TI  - Knowledge and practices of teachers associated with eye health of primary school
      children in Rawalpindi, Pakistan.
AB  - PURPOSE: Teachers' perspectives on eye health can be limited, particularly in
      developing countries. The aim of this study was to assess teachers' knowledge and
      practices associated with eye health of primary students in Rawalpindi, Pakistan.
      METHODS: This was a cross-sectional survey of primary school teachers. Simple
      random sampling technique was used to select 443 participants from 34 private and
      17 public schools. A self-administered questionnaire was used. RESULTS: Teachers'
      knowledge ranged from "high" (35.89%), "moderate" (49.89%), and "low" (14.22%).
      Teachers' practices associated with students' eye health ranged from "high"
      (10.16%), "moderate" (23.02%), and "low" (66.82%). The teachers' knowledge index
      scores increased 4.28 points with successive age groups and increased 2.41 points
      with each successive level of education. For teachers whose close relatives
      experienced eye disease, their knowledge index score was 4.51 points higher than
      those teachers whose relatives never had any eye disease. Teachers' age,
      education level, and their close relatives experiencing eye disease were
      significant predictors of their knowledge (R2 = 0.087, P < 0.001). Female
      teachers' practices index score was 10.35 points higher than the male teachers
      and public school teachers had 10.13 points higher than the private school
      teachers. Teachers' gender and type of school were significant predictors of
      their practices (R2 = 0.06, P < 0.001). CONCLUSION: There was a significant gap
      among primary school teachers' knowledge and practices related to students' eye
      health. Innovative strategies are needed to improve how teachers address
      students' eye health issues in the classroom.

PMID- 29018752
TI  - Y-splitting with recession of lateral rectus versus lateral rectus recession in
      correcting upshoot in Duane retraction syndrome.
AB  - PURPOSE: To report the surgical effect in upshoot of Duane retraction syndrome
      (DRS) with corecession of horizontal rectus muscles with or without Y-splitting.
      PATIENTS AND METHODS: A retrospective chart review of six patients of DRS
      received muscle surgeries for upshoot in adducted position was performed.
      RESULTS: From 1994 to 2010, six Duane patients received muscle surgeries for
      upshoots of lesion eye in adduction. Their age of receiving surgery ranged from 5
      to 41 years. Four of the patients were male, and five had their left eye
      involved. Three underwent recession of ipsilateral medial and lateral rectus (LR)
      muscles, and the other three also received Y-splitting of LR muscle when
      recession. One of the patients that received Y-splitting showed mild hypertropia
      at down gaze postoperatively, and another one had little improvement of exotropia
      at the primary position. All patients showed improvement of their upshoots and
      lid fissure narrowing in adduction as well as face turn. CONCLUSION:
      Postoperative improvements in abnormal head posture and upshoots were achieved
      with corecession of horizontal muscles with or without Y-splitting. Although Y
      splitting of the LR muscle is an effective surgery, it might cause undesired
      complications.

PMID- 29018753
TI  - Adjustable suture strabismus surgery in pediatric patients using pull-string
      technique.
AB  - BACKGROUND/PURPOSE: The concept of adjustable suture has been developed in
      strabismus surgeries for nearly four decades. This technique is not yet
      universally embraced by strabismus surgeons, especially in pediatric patients.
      The aim of this study is to describe and evaluate the application of the
      adjustable suture with pull-string technique in pediatric patients. METHODS: A
      retrospective medical record review was conducted for patients aged 18 years and
      under who received adjustable suture strabismus surgery using short tag sliding
      noose with pull-string technique. For the analysis, the patients were arbitrarily
      divided into three age groups: 6 years and younger, between 6 and 12 years, and
      12 years and older. Patients were examined at 1 week and 1, 3, and 6 months after
      surgery. RESULTS: A total of 123 patients were enrolled in this study. The mean
      age at the time of surgery was 9.4 years, ranging from 0.7 to 18.4 years.
      Eighteen (14.6%) patients required adjustment and 105 (85.4%) patients did not
      require adjustment. The average follow-up was 10.2 months (range, 1-48 months).
      At their final postoperative follow-up, 93 of 123 (75.6%) patients were within 10
      prism diopters of orthophoria. The success rates were 77.6% (66/85) in exotropia
      patients and 71.1% (27/38) in esotropia patients. The success rates were 76.4%
      (84/110) for those who receive the procedure as primary surgery and 69.2% (9/13)
      for those who receive the procedure as reoperative surgery. Of the 18 patients
      who required adjustment, 16 (88.9%) patients were successful. Of the 105 patients
      who did not require adjustment, 77 (73.3%) patients were successful. CONCLUSION:
      This study showed that the pull-string technique provided similar success rate
      compared to those reported in literature in pediatric patients. The pull-string
      technique is developed to simplify the postoperative adjustments. Many surgeons
      encounter difficulties to handle the postoperative adjustments, especially when
      they need to retrieve the buried subconjunctival adjustable sutures. The
      obstacles are reduced with the aid of pull string. Using the pull-string
      technique, the surgeon can perform adjustable suture surgeries in any age group
      with confidence.

PMID- 29018754
TI  - How to effectively manage myopia.
AB  - Myopia has become epidemic in the world. Without effective control, the
      progression may lead to excessive myopia with severe complications affecting
      vision and ocular alignment. The genetic factors and environmental factors of
      myopia are closely interrelated to each other. Asian ethnicity and parental
      myopia, among other genetic factors, influence the refractive outcome
      dramatically when environmental risk factors such as hours of near work and
      reading distance are analyzed. Outdoor activities are protective measures that
      retard myopia progression. Total time under the sun and not the specific outdoor
      activities are contributing factors. Current effective treatments for myopia
      include atropine of high, moderate, and low doses, relative peripheral myopia
      inducing devices, and bifocal spectacles including prism bifocal spectacle
      lenses. Although atropine is considered highly effective in randomized controlled
      trials, it is not well tolerated in a clinical setting, especially in high
      dosage. Since the severity of rebound effect of atropine after cessation of usage
      and the side effects are directly related to the concentration of the medication,
      it is recommended that low-dose atropine is used in the initial attempt. Higher
      concentration for better control can be considered when compliance is observed.
      Devices that induce relative peripheral myopia such as orthokeratology are
      moderately effective interventions that are well accepted by children who wish to
      be spectacle free. Bifocal spectacles generally have low effect in myopia
      control. Prism bifocal spectacle lenses may have a special niche in myopia
      retardation for patients with low lags of accommodation.

PMID- 29018755
TI  - Vertical diplopia after cataract surgery, overacting, and/or underacting
      extraocular muscle.
AB  - The purpose of this study was to demonstrate two cases of vertical diplopia after
      cataract surgery and to discuss the mechanism and types of strabismus caused by
      the local anesthesia with retrobulbar injection. Two cases of vertical diplopia
      after cataract surgeries were reported. They were operated by the same surgeon
      and both happened to the left eye and both presented with marked left hypotropia.
      The clinical findings consisted of overacting left inferior rectus (LIR) in case
      1 and mixed overacting and restrictive LIR in case 2. The diplopia and left
      hypotropia were eliminated after muscle operation. Retrobulbar injection is a
      basic technique in ophthalmic practice. Although it is generally safe,
      complications do happen in certain cases including diplopia and strabismus.
      Ophthalmologists should know about the orbital anatomy and learn to prevent any
      accidental insult to extraocular muscles.

PMID- 29018756
TI  - Descemet's Stripping-automated Endothelial Keratoplasty for symptomatic
      thioridazine deposits in the cornea.
AB  - The aim of this study was to use Descemet's Stripping-automated Endothelial
      Keratoplasty (DSAEK) as a novel treatment to remove thioridazine corneal
      deposits. A 53-year-old female presented with a 3-month history of visual loss
      and glare. She had been taking thioridazine (100 mg/day for 1 year) for a
      psychiatric disorder. Dense yellowish-brown deposits had developed in the
      posterior stroma. Thioridazine was discontinued, and she was switched to
      fluoxetine. One year after discontinuation of thioridazine, her symptoms and
      signs did not resolve. Standard DSAEK was performed on her left eye. Two weeks
      after DSAEK, an anterior subcapsular cataract was detected in the same eye.
      Phacoemulsification and intraocular lens implantation were performed after 3
      months. The left cornea became completely clear after DSAEK, and the patient's
      best-corrected visual acuity improved from 20/40 to 20/20 at 1 month after
      cataract surgery. All-visual symptoms such as glare and halos improved
      postoperatively. We suggest that DSAEK can be used as a novel treatment to reduce
      vision problems caused by thioridazine-induced corneal deposits.

PMID- 29018757
TI  - Macular edema might be a rare presentation of hydroxychloroquine-induced retinal
      toxicity.
AB  - The aim of this study is to report a rare case of macular edema as a presentation
      of hydroxychloroquine-related retinal toxicity. We presented a case of a 46-year
      old female patient using hydroxychloroquine for underlying rheumatoid arthritis
      (RA) with blurred vision over the left eye. Uveitis and macular edema were found
      initially. Systemic survey did not reveal any other etiology. Topical
      corticosteroid was given under the impression of RA-related uveitis. The uveitis
      resolved 1 week later, but macular edema persisted in spite of treatment. Under
      the suspicion of drug-related complication, we try to discontinue
      hydroxychloroquine. Her symptoms improved gradually after cessation of
      hydroxychloroquine, and further serial image study confirmed subsiding of the
      macular edema without any further treatment. Except the well-known signs of the
      retinal toxicity, macular edema might be a rare presentation of
      hydroxychloroquine-related retinal toxicity.

PMID- 29018758
TI  - Therapy for Amblyopia: A newer perspective.

PMID- 29018760
TI  - Management of macular edema due to central retinal vein occlusion - The role of
      aflibercept.
AB  - Central retinal vein occlusion (CRVO) can cause vision loss. The pathogenesis of
      CRVO involves a thrombus formation leading to increased retinal capillary
      pressure, increased vascular permeability, and possibly retinal
      neovascularization. Vision loss due to CRVO is commonly caused by macular edema.
      Multiple treatment modalities have been used to treat macular edema. Currently,
      the most common therapy used is intravitreal inhibition of vascular endothelial
      growth factor (VEGF). The three most widely used agents are aflibercept,
      bevacizumab, and ranibizumab and they are effective at blocking VEGF. In
      addition, intraocular steroids can be used to treat macular edema. This review
      will briefly cover the treatment options and discuss in greater detail the
      efficacy and safety of aflibercept.

PMID- 29018759
TI  - Pharmacological therapy for amblyopia.
AB  - Amblyopia is the most common cause of preventable blindness in children and young
      adults. Most of the amblyopic visual loss is reversible if detected and treated
      at appropriate time. It affects 1.0 to 5.0% of the general population. Various
      treatment modalities have been tried like refractive correction, patching (both
      full time and part time), penalization and pharmacological therapy. Refractive
      correction alone improves visual acuity in one third of patients with
      anisometropic amblyopia. Various drugs have also been tried of which carbidopa &
      levodopa have been popular. Most of these agents are still in experimental stage,
      though levodopa-carbidopa combination therapy has been widely studied in human
      amblyopes with good outcomes. Levodopa therapy may be considered in cases with
      residual amblyopia, although occlusion therapy remains the initial treatment
      choice. Regression of effect after stoppage of therapy remains a concern. Further
      studies are therefore needed to evaluate the full efficacy and side effect
      profile of these agents.

PMID- 29018761
TI  - Using stem cell biology to study and treat ophthalmologic and oculoplastic
      diseases.
AB  - With the rapid growth of the stem cell biology field, the prospect of
      regenerative medicine across multiple tissue types comes closer to reality.
      Several groundbreaking steps paved the way for applying stem cell biology to the
      several subfields within ophthalmology and oculoplastic surgery. These steps
      include the use of stem cell transplants as well as studies of various
      ophthalmologic pathologies at the molecular level. The necessity of stem cell
      transplant is readily apparent, having already been used for several studies such
      as artificial lacrimal gland design and eyelid reconstruction. Investigating the
      stem cell biology behind oncological diseases of the eye has also developed
      recently, such as with the identification of specific markers to label cancer
      stem cells in orbital adenoid cystic carcinoma. The advent of induced pluripotent
      stem cells led to a burst of productivity in the field of regenerative medicine,
      making it possible to take a patient's own cells, reprogram them, and use them to
      either study patient-specific pathology in vitro or use them for eventual patient
      specific therapeutics. Patient-specific adipose-derived stem cells (ASCs) have
      been used for a variety of treatments, such as wound healing and burn therapies.
      As the fields of stem cell biology and regenerative medicine continue to
      progress, its use will become a mainstay of patient-specific cell therapies in
      the future.

PMID- 29018762
TI  - Visual performance after excimer laser photorefractive keratectomy for high
      myopia.
AB  - PURPOSE: To evaluate the efficacy, safety, predictability, and visual performance
      of excimer laser photorefractive keratectomy (PRK) for myopia greater than -8
      diopters (D). METHODS: Fifty-four patients (104 eyes) with myopia from -8D to 
      13D and cylinder up to -4D received surface ablation technique with the
      Allegretto wave version 1009-1 excimer laser to correct their refractive error.
      The patients were examined on days 1, 3, 7, and 14 and 1, 3, 6, and 12 months
      postoperatively. Visual acuity, manifest refraction, corneal haze, topography,
      intraocular pressure, contrast sensitivity, and wavefront aberration were
      evaluated. RESULTS: Twelve months postoperatively, 95% of eyes were within 1D of
      the intended correction. In addition, 94% of eyes had attained uncorrected
      distance visual acuity of 20/25 or better, and 98% of eyes had improved or
      remained their corrected distance visual acuity. All eyes exhibited barely
      detectable corneal haze which peaked during the 1st month with a gradual
      reduction in the 3rd month. Ninety-five percent of patients had no or only mild
      degree of night glare. CONCLUSIONS: Excimer laser PRK is an effective and
      predictive treatment for high myopia greater than -8D with or without astigmatism
      up to -4D. The incidence of complication is low. All patients who are candidates
      for laser in situ keratomileusis can be candidates for surface ablation,
      especially those with preoperative thinner cornea or higher risk of corneal flap
      complications.

PMID- 29018763
TI  - Ocular manifestations of sickle cell disease and genetic susceptibility for
      refractive errors.
AB  - PURPOSE: Sickle cell disease (SCD) is the most common and serious form of an
      inherited blood disorder that lead to higher risk of early mortality. SCD
      patients are at high risk for developing multiorgan acute and chronic
      complications linked with significant morbidity and mortality. Some of the
      ophthalmological complications of SCD include retinal changes, refractive errors,
      vitreous hemorrhage, and abnormalities of the cornea. MATERIALS AND METHODS: The
      present study includes 96 SCD patients. A dilated comprehensive eye examination
      was performed to know the status of retinopathy. Refractive errors were measured
      in all patients. In patients with >10 years of age, cycloplegia was not performed
      before autorefractometry. A subset of fifty patients' genotyping was done for
      NOS3 27-base pair (bp) variable number of tandem repeat (VNTR) and IL4 intron-3
      VNTR polymorphisms using polymerase chain reaction-electrophoresis. Chi-square
      test was performed to test the association between the polymorphisms and
      refractive errors. RESULTS: The results of the present study revealed that 63.5%
      of patients have myopia followed by 19.8% hyperopia. NOS3 27-bp VNTR genotypes
      significantly deviated from Hardy-Weinberg equilibrium (P < 0.0001). Although IL4
      70-bp VNTR increased the risk of developing refractive errors, it is not
      statistically significant. However, NOS3 27-bp VNTR significantly reduced the
      risk of development of myopia. CONCLUSION: In summary, our study documents the
      prevalence of refractive errors along with some retinal changes in Indian SCD
      patients. Further, this study demonstrates that the NOS3 VNTR contributes to the
      susceptibility to development of myopia in SCD cases.

PMID- 29018765
TI  - Surgical results for consecutive exotropia.
AB  - PURPOSE: To evaluate the surgical results of medial rectus (MR) muscle
      advancement with or without recession of the antagonist muscle for consecutive
      exotropia. METHODS: Medical records of patients with consecutive exotropia (n =
      27) were retrospectively reviewed. All patients received one-eye surgery with MR
      advancement, lateral rectus (LR) recession, or combined surgery. The pre- and
      post-operative angle of deviation was recorded. Characteristics were compared
      between groups. The follow-up period was at least 3 months. RESULTS: The overall
      successful rate was 62.96%, with 50% in MR advancement group, 60% in LR recession
      group, and 71.4% in combined group. Patients in combined group had larger
      preoperative deviation. There were comparable surgical results between patients
      with inferior oblique (IO) muscle overaction receiving correction simultaneously
      and patients without IO muscle overaction. CONCLUSIONS: The overall surgical
      successful rate for consecutive exotropia in this study was 62.96%. Combined MR
      advancement and LR recession yielded better results than MR advancement or LR
      recession alone although it was not statistically significant.

PMID- 29018764
TI  - Scleral buckling-induced ocular parameter changes in different age group patients
      of rhegmatogenous retinal detachment.
AB  - PURPOSE: This study was aimed to evaluate the difference in the ocular parameter
      changes following scleral buckling (SB) for rhegmatogenous retinal detachment
      (RRD) in different age group patients. MATERIALS AND METHODS: This prospective
      study included 26 eyes of 26 patients who underwent SB for uncomplicated RRD. The
      patients were divided into three age groups: 16-30 years (Group I), 31-45 years
      (Group II), and 46-60 years (Group III). Axial length (AL), anterior chamber
      depth (ACD), and corneal curvatures were measured preoperatively and
      postoperatively at 1 week, 1 month, and 3-month. The postoperative change and
      progression of these parameters were evaluated and compared between three age
      groups using nonparametric Wilcoxon signed-rank test and Kruskal-Wallis test.
      RESULTS: At 3-month follow-up, a statistically significant postoperative AL
      increase, ACD decrease, and surgically induced astigmatism (SIA) were observed in
      all groups (Group I - 0.75 +/- 0.32 mm, 0.21 +/- 0.21 mm, and 1.5 +/- 0.48 D,
      respectively; Group II - 0.79 +/- 0.41 mm, 0.14 +/- 0.04 mm, and 2.07 +/- 1.18 D,
      respectively; Group III - 0.86 +/- 0.33 mm, 0.16 +/- 0.05 mm, and 1.56 +/- 1.19
      D, respectively). However, surgery-induced change for any parameter was not
      significantly different between the groups (P for AL [0.7955]; ACD [0.8805]; and
      SIA [0.5485]). Progression in postoperative changes in AL and ACD was
      insignificant during three follow-up examinations in all the groups. However, SIA
      of Group I continued to change significantly up to 3 months but stopped to change
      at 1 month only in Group II and III. CONCLUSION: Age-related change in physical
      properties of ocular tissue does not have any major additional effect on the
      results of SB except that the postsurgical change in corneal curvature stops
      earlier in older patients compared to that in younger patients.

PMID- 29018766
TI  - Acute angle closure following periorbital botulinum toxin injection in a patient
      with retinitis pigmentosa.
AB  - A 50-year-old female presented with bilateral retinitis pigmentosa (RP) and acute
      angle closure (AAC) with fixed mid-dilated pupil and high intraocular pressure
      (IOP) in the left eye following left side periorbital botulinum toxin A injection
      for blepharospasm. Glaucomatous optic neuropathy and retinal nerve fiber layer
      defect were observed in the affected eye using optical coherence tomography
      although the IOP was maintained at <21 mmHg after the treatment. Botulinum toxin
      acts at the cholinergic synapse and inhibits acetylcholine release; hence, it can
      cause transient mydriasis and may lead to AAC in high-risk populations such as
      patients with RP. Patients should be explained about the possible development of
      mydriasis associated with botulinum toxin injection, and clinicians must evaluate
      the level of risk for AAC before administration of botulinum toxin around the
      eyelid. In cases showing side effects associated with botulinum toxin injection,
      early diagnosis and treatment is required to prevent blindness.

PMID- 29018767
TI  - Optical coherence tomography features in a case of Type I sialidosis.
AB  - A 15-year-old boy presented with progressive myoclonic epilepsy and unbalance
      gaits for 4 years. Slit lamp examination showed a punctate cataract and
      funduscopic examination revealed bilateral macular cherry-red spots. Macular scan
      of spectral domain optical coherence tomography (SD-OCT) showed hyperreflectivity
      of the inner retinal layer and apparent hyperreflectivity of the photoreceptor
      layers in the foveal region. The clinical presentations were consistent with a
      Type I sialidosis which led to genetic analysis and revealed NEU1 mutation in
      this patient. He was under regular follow-up by ophthalmologist and neurologist.
      Sialidosis is a rare lysosomal storage disease resulting from a deficiency of
      alpha-N-acetyl neuraminidase caused by a mutation in the NEU1 gene. This results
      in abnormal intracellular accumulation of sialyloligosaccharides in brain neurons
      and ganglion cells of the retina. SD-OCT is a useful tool in detecting macular
      cherry-red spot and has a role in evaluating the extent of ganglion cell damage.
      It can aid in the differential diagnosis and long-term follow-up of the
      neurological metabolic disorders.

PMID- 29018768
TI  - Soft tissue recurrence of giant cell tumor of the bone: Prevalence and
      radiographic features.
AB  - AIM: Recurrence of giant cell tumor of bone (GCTB) in the soft tissue is rarely
      seen in the clinical practice. This study aims to determine the prevalence of
      soft tissue recurrence of GCTB, and to characterize its radiographic features.
      METHODS: A total of 291 patients treated by intralesional curettage for
      histologically diagnosed GCTB were reviewed. 6 patients were identified to have
      the recurrence of GCTB in the soft tissue, all of whom had undergone marginal
      resection of the lesion. Based on the x-ray, CT and MRI imaging, the radiographic
      features of soft tissue recurrence were classified into 3 types. Type I was
      defined as soft tissue recurrence with peripheral ossification, type II was
      defined as soft tissue recurrence with central ossification, and type III was
      defined as pure soft tissue recurrence without ossification. Demographic data
      including period of recurrence and follow-up duration after the second surgery
      were recorded for these 6 patients. Musculoskeletal Tumor Society (MSTS) scoring
      system was used to evaluate functional outcomes. RESULTS: The overall recurrence
      rate was 2.1% (6/291). The mean interval between initial surgery and recurrence
      was 11.3 +/- 4.1 months (range, 5-17). The recurrence lesions were located in the
      thigh of 2 patients, in the forearm of 2 patients and in the leg of the other 2
      patients. According to the classification system mentioned above, 2 patients were
      classified with type I, 1 as type II and 3 as type III. After the marginal
      excision surgery, all patients were consistently followed up for a mean period of
      13.4 +/- 5.3 months (range, 6-19), with no recurrence observed at the final
      visit. All the patients were satisfied with the surgical outcome. According to
      the MSTS scale, the mean postoperative functional score was 28.0 +/- 1.2 (range,
      26-29). CONCLUSIONS: The classification of soft tissue recurrence of GCTB may be
      helpful for the surgeon to select the appropriate imaging procedure to detect the
      recurrence. In addition, the marginal resection can produce a favorable outcome
      for the patients.

PMID- 29018769
TI  - Homeless shelter context and tuberculosis illness experiences during a large
      outbreak in Atlanta, Georgia.
AB  - Setting: Persons experiencing homelessness (PEH) represent a population at high
      risk for tuberculosis (TB). While quantitative studies have characterized some
      important features of this key group, less has been captured directly from PEH
      about how they experience TB illness itself and the prevention and control
      measures implemented in response to an outbreak. This qualitative study aimed to
      explore PEH's TB disease experiences in the context of a large TB outbreak
      involving homeless shelters in Atlanta, Georgia, USA. Design: This was a
      qualitative cross-sectional study involving in-depth interviews with 10 PEH with
      active TB disease. Key themes were identified through coded data analysis.
      Results: The central theme to emerge was that stressful social environments of
      homeless shelters shape illness experiences and health care seeking behaviors,
      and limit the influence of shelter-based prevention and control measures
      implemented in response to a TB outbreak. Despite availability, shelter-based
      latent tuberculous infection (LTBI) testing and education services were minimally
      engaged. Furthermore, hardships inherent to homelessness were interrelated with
      disease normalization and symptom minimization. Conclusions: Homeless shelter
      related stress may have important implications for the prevention and control of
      TB outbreaks in this setting. This stress may hinder case finding; a model of
      supplemental TB education and testing for LTBI at proximal community venues is
      necessary.

PMID- 29018770
TI  - Master of Science (MSc) Program in Radiation Biology: An Interdepartmental Course
      Bridging the Gap between Radiation-Related Preclinical and Clinical Disciplines
      to Prepare Next-Generation Medical Scientists.
AB  - Radiation biology is a highly interdisciplinary field at the interface of
      biology, physics, and medicine. It is characterized by rapid advances in
      biological and technical knowledge. The potential for using these advances to
      optimize medical care, radiation protection, and related fields can be exploited
      only with complementary activities to support the education of young academics. A
      small number of academic institutions have committed resources into radiation
      related courses and curricula; however, few offer a comprehensive
      interdepartmental research and training program. At the Technical University of
      Munich (TUM), a full Master of Science (MSc) course in radiation biology has been
      established. This article describes the TUM MSc radiation biology program,
      discusses the scope of the field, the teaching goals, and the interdisciplinary
      curriculum. Detailed information on the full MSc program can be found
      continuously updated at www.radonc.med.tum.de/masterradiationbiology.

PMID- 29018772
TI  - Editorial: Cancer Metabolism: Molecular Targeting and Implications for Therapy.

PMID- 29018774
TI  - Influenza A Virus as a Predisposing Factor for Cryptococcosis.
AB  - Influenza A virus (IAV) infects millions of people annually and predisposes to
      secondary bacterial infections. Inhalation of fungi within the Cryptococcus
      complex causes pulmonary disease with secondary meningo-encephalitis. Underlying
      pulmonary disease is a strong risk factor for development of C. gattii
      cryptococcosis though the effect of concurrent infection with IAV has not been
      studied. We developed an in vivo model of Influenza A H1N1 and C. gattii co
      infection. Co-infection resulted in a major increase in morbidity and mortality,
      with severe lung damage and a high brain fungal burden when mice were infected in
      the acute phase of influenza multiplication. Furthermore, IAV alters the host
      response to C. gattii, leading to recruitment of significantly more neutrophils
      and macrophages into the lungs. Moreover, IAV induced the production of type 1
      interferons (IFN-alpha4/beta) and the levels of IFN-gamma were significantly
      reduced, which can be associated with impairment of the immune response to
      Cryptococcus during co-infection. Phagocytosis, killing of cryptococci and
      production of reactive oxygen species (ROS) by IAV-infected macrophages were
      reduced, independent of previous IFN-gamma stimulation, leading to increased
      proliferation of the fungus within macrophages. In conclusion, IAV infection is a
      predisposing factor for severe disease and adverse outcomes in mice co-infected
      with C. gattii.

PMID- 29018777
TI  - Rationale, Feasibility and Acceptability of Ketogenic Diet for Cancer Treatment.
AB  - Ketogenic diet has been used for more than 80 years as a successful dietary
      regimen for epilepsy. Recently, dietary modulation by carbohydrate depletion via
      ketogenic diet has been suggested as an important therapeutic strategy to
      selectively kill cancer cells and as adjuvant therapy for cancer treatment.
      However, some researchers insist ketogenic diet to be highly undesirable as
      ketogenic diet may trigger and/or exacerbate cachexia development and usually
      result in significant weight loss. This review revisits the meaning of
      physiological ketosis in the light of this evidence and considers possibility of
      the use of ketogenic diet for oncology patients. Article search was performed
      from 1985 through 2017 and finally 10 articles were analyzed. The review focused
      on the results of human trials for cancer patients and checked the feasibility of
      using ketogenic diet for cancer patients as adjuvant therapy. The main outcomes
      showed improvement of body weight changes, anthropometric changes, serum blood
      profiles, and reduction in novel marker for tumor progression, TKTL1, and
      increase of ketone body. Lactate concentration was reduced, and no significant
      changes were reported in the measurements of quality of life. Ketogenic diet may
      be efficacious in certain cancer subtypes whose outcomes appear to correlate with
      metabolic status, but the results are not yet supportive and inconsistent.
      Therefore, it warrants further studies.

PMID- 29018776
TI  - Impaired Cellular Energy Metabolism Contributes to Duck-Enteritis-Virus-Induced
      Autophagy via the AMPK-TSC2-MTOR Signaling Pathway.
AB  - Duck enteritis virus (DEV) is a large, complex double-stranded DNA virus that
      induces duck embryo fibroblast (DEF) cells autophagy, which is beneficial to its
      own replication, but the mechanism has not been described. In this study, we
      showed that impaired cell energy metabolism is involved in DEV-induced autophagy,
      whereby ATP synthesis is disrupted in cells after DEV infection, which causes
      metabolic stress and activation of autophagy. Methyl pyruvate (MP) inhibited
      conversion of LC3I to LC3II and accumulation of GFP-LC3, which could reverse the
      energy loss caused by DEV infection. Inhibition of DEV replication by MP
      confirmed the above view. We found that infection with DEV activated the
      metabolic regulator 5' AMP-activated kinase (AMPK) and inhibited activity of
      mechanistic target of rapamycin (mTOR). In the cases where AMPK expression was
      inhibited, the LC3-I conversion to LC3-II ratio was decreased, as was GFP-LC3
      point and DEV replication; in addition, inhibition of p-mTOR showed a reverse
      trend. We also found that tuberous sclerosis (TSC) 2 was a key mediator between
      AMPK and mTOR through activation by phosphorylation. siRNA targeting TSC2 was
      transfected to reverse the inhibition of mTOR, and down-regulate autophagy level
      and DEV replication, but AMPK expression was not changed, while siRNA targeting
      AMPK inhibited activation of TSC2. In conclusion, our findings indicate that
      energy metabolism in cell damage induced by DEV contributes to autophagy via the
      AMPK-TSC2-MTOR signaling pathway, which provides a new perspective for DEV and
      host interactions.

PMID- 29018771
TI  - Targeting Nucleotide Biosynthesis: A Strategy for Improving the Oncolytic
      Potential of DNA Viruses.
AB  - The rapid growth of tumors depends upon elevated levels of dNTPs, and while dNTP
      concentrations are tightly regulated in normal cells, this control is often lost
      in transformed cells. This feature of cancer cells has been used to advantage to
      develop oncolytic DNA viruses. DNA viruses employ many different mechanisms to
      increase dNTP levels in infected cells, because the low concentration of dNTPs
      found in non-cycling cells can inhibit virus replication. By disrupting the virus
      encoded gene(s) that normally promote dNTP biosynthesis, one can assemble
      oncolytic versions of these agents that replicate selectively in cancer cells.
      This review covers the pathways involved in dNTP production, how they are
      dysregulated in cancer cells, and the various approaches that have been used to
      exploit this biology to improve the tumor specificity of oncolytic viruses. In
      particular, we compare and contrast the ways that the different types of
      oncolytic virus candidates can directly modulate these processes. We limit our
      review to the large DNA viruses that naturally encode homologs of the cellular
      enzymes that catalyze dNTP biogenesis. Lastly, we consider how this knowledge
      might guide future development of oncolytic viruses.

PMID- 29018773
TI  - Activity of Bacteriophages in Removing Biofilms of Pseudomonas aeruginosa
      Isolates from Chronic Rhinosinusitis Patients.
AB  - Introduction:Pseudomonas aeruginosa infections are prevalent amongst chronic
      rhinosinusitis (CRS) sufferers. Many P. aeruginosa strains form biofilms, leading
      to treatment failure. Lytic bacteriophages (phages) are viruses that infect,
      replicate within, and lyse bacteria, causing bacterial death. Aim: To assess the
      activity of a phage cocktail in eradicating biofilms of ex vivo P.aeruginosa
      isolates from CRS patients. Methods: P. aeruginosa isolates from CRS patients
      with and without cystic fibrosis (CF) across three continents were multi-locus
      sequence typed and tested for antibiotic resistance. Biofilms grown in vitro were
      treated with a cocktail of four phages (CT-PA). Biofilm biomass was measured
      after 24 and 48 h, using a crystal violet assay. Phage titrations were performed
      to confirm replication of the phages. A linear mixed effects model was applied to
      assess the effects of treatment, time, CF status, and multidrug resistance on the
      biomass of the biofilm. Results: The isolates included 44 strain types. CT-PA
      treatment significantly reduced biofilm biomass at both 24 and 48 h post
      treatment (p < 0.0001), regardless of CF status or antibiotic resistance. Biomass
      was decreased by a median of 76% at 48 h. Decrease in biofilm was accompanied by
      a rise in phage titres for all except one strain. Conclusion: A single dose of
      phages is able to significantly reduce biofilms formed in vitro by a range of
      P.aeruginosa isolates from CRS patients. This represents an exciting potential
      and novel targeted treatment for P. aeruginosa biofilm infections and multidrug
      resistant bacteria.

PMID- 29018775
TI  - Giardia's Epithelial Cell Interaction In Vitro: Mimicking Asymptomatic Infection?
AB  - The protozoan parasite Giardia duodenalis is responsible for more than 280
      million cases of gastrointestinal complaints ("giardiasis") every year,
      worldwide. Infections are acquired orally, mostly via uptake of cysts in
      contaminated drinking water. After transformation into the trophozoite stage,
      parasites start to colonize the duodenum and upper jejunum where they attach to
      the intestinal epithelium and replicate vegetatively. Outcome of Giardia
      infections vary between individuals, from self-limiting to chronic, and
      asymptomatic to severely symptomatic infection, with unspecific gastrointestinal
      complaints. One proposed mechanism for pathogenesis is the breakdown of
      intestinal barrier function. This has been studied by analyzing trans-epithelial
      electric resistances (TEER) or by indicators of epithelial permeability using
      labeled sugar compounds in in vitro cell culture systems, mouse models or human
      biopsies and epidemiological studies. Here, we discuss the results obtained
      mainly with epithelial cell models to highlight contradictory findings. We relate
      published studies to our own findings that suggest a lack of barrier compromising
      activities of recent G. duodenalis isolates of assemblage A, B, and E in a Caco-2
      model system. We propose that this epithelial cell model be viewed as mimicking
      asymptomatic infection. This view will likely lead to a more informative use of
      the model if emphasis is shifted from aiming to identify Giardia virulence
      factors to defining non-parasite factors that arguably appear to be more decisive
      for disease.

PMID- 29018778
TI  - Cancer-preventive Properties of an Anthocyanin-enriched Sweet Potato in the
      APCMIN Mouse Model.
AB  - BACKGROUND: Anthocyanin-rich foods and preparations have been reported to reduce
      the risk of life-style related diseases, including cancer. The SL222 sweet
      potato, a purple-fleshed cultivar developed in New Zealand, accumulates high
      levels of anthocyanins in its storage root. METHODS: We examined the
      chemopreventative properties of the SL222 sweet potato in the C57BL/6J-APC MIN/+
      (APCMIN) mouse, a genetic model of colorectal cancer. APCMIN and C57BL/6J wild
      type mice (n=160) were divided into four feeding groups consuming diets
      containing 10% SL222 sweet potato flesh, 10% SL222 sweet potato skin, or 0.12%
      ARE (Anthocyanin rich-extract prepared from SL222 sweet potato at a concentration
      equivalent to the flesh-supplemented diet) or a control diet (AIN-76A) for 18
      weeks. At 120 days of age, the mice were anaesthetised, and blood samples were
      collected before the mice were sacrificed. The intestines were used for adenoma
      enumeration. RESULTS: The SL222 sweet potato-supplemented diets reduced the
      adenoma number in the APCMIN mice. CONCLUSIONS: These data have significant
      implications for the use of this sweet potato variant in protection against
      colorectal cancer.

PMID- 29018779
TI  - Differential Tissue-specific and Pathway-specific Anti-obesity Effects of Green
      Tea and Taeumjowitang, a Traditional Korean Medicine, in Mice.
AB  - BACKGROUND: Traditional medicines have been leveraged for the treatment and
      prevention of obesity, one of the fastest growing diseases in the world. However,
      the exact mechanisms underlying the effects of traditional medicine on obesity
      are not yet fully understood. METHODS: We produced the transcriptomes of
      epididymal white adipose tissue (eWAT), liver, muscle, and hypothalamus harvested
      from mice fed a normal diet, high-fat-diet alone, high-fat-diet together with
      green tea, or a high-fat-diet together with Taeumjowitang, a traditional Korean
      medicine. RESULTS: We found tissue-specific gene expression patterns as follows:
      (i) the eWAT transcriptome was more significantly altered by Taeumjowitang than
      by green tea, (ii) the liver transcriptome was similarly altered by Taeumjowitang
      and green tea, and (iii) both the muscle and hypothalamus transcriptomes were
      more significantly altered by green tea than Taeumjowitang. We then applied
      integrated network analyses, which revealed that functional networks associated
      with lymphocyte activation were more effectively regulated by Taeumjowitang than
      by green tea in the eWAT. In contrast, green tea was a more effective regulator
      of functional networks associated with glucose metabolic processes in the eWAT.
      CONCLUSIONS: Taeumjowitang and green tea have a differential tissue-specific and
      pathway-specific therapeutic effect on obesity.

PMID- 29018781
TI  - Association Between Health Behaviors and Family History of Cancer in Cancer
      Survivors: Data From the Korean Genome and Epidemiology Study.
AB  - BACKGROUND: We compared health behaviors, including current smoking, alcohol
      drinking, regular exercise, obesity, and abdominal obesity, among Korean cancer
      survivors with and without family history of cancer. METHODS: This study included
      5,247 cancer survivors with family history of cancer (1,894 with and 3,353
      without), who were recruited from the Health Examinee cohort. Health behaviors
      were identified using questionnaire. Adjusted ORs (aORs) between health behaviors
      and family history of cancer were estimated by multivariate logistic regression
      analysis adjusted for sociodemographic factors. All analyses were conducted
      separately according to sex. RESULTS: Prevalence of current smoking, alcohol
      drinking, no regular exercise, obesity, and abdominal obesity was 16.3%, 48.3%,
      36.0%, 31.3%, and 42.3% in male cancer survivors and 1.7%, 20.6%, 43.8%, 28.5%,
      and 72.5% in female, respectively. Health behaviors in male cancer survivors with
      and without family history of cancer were not significantly different after being
      adjusted for other covariates (aOR = 1.04, 95% CI = 0.75-1.44 for current
      smoking; aOR = 0.96, 95% CI = 0.76-1.22 for current drinking; aOR = 0.85, 95% CI
      = 0.66-1.10 for regular exercise; aOR = 0.96, 95% CI = 0.73-1.25 for obesity; aOR
      = 0.97, 95% CI = 0.75-1.25 for abdominal obesity). In female cancer survivors,
      there were no significant differences in health behaviors according to family
      history of cancer (aOR = 0.76, 95% CI = 0.44-1.32; aOR = 1.11, 95% CI = 0.94
      1.31; aOR = 0.99, 95% CI = 0.87-1.14; aOR = 0.99, 95% CI = 0.85-1.16; aOR = 0.93,
      95% CI = 0.80-1.10, respectively). CONCLUSIONS: We identified no significant
      differences in health behaviors according to family history of cancer in cancer
      survivors. More studies should be conducted to identify correlations between
      family history of cancer and prognosis in cancer survivors.

PMID- 29018782
TI  - Comparison of Blueberry (Vaccinium spp.) and Vitamin C via Antioxidative and
      Epigenetic Effects in Human.
AB  - BACKGROUND: Chemopreventive effects and the underlying mechanisms of blueberry
      (Vaccinium spp.) are not clearly understood in human. We hypothesized blueberry
      would work via antioxidative and epigenetic modulation, which is similar to
      vitamin C. METHODS: We performed a pilot and non-inferiority study in healthy
      young women (n = 12), who consumed vitamin C (1 g/d) or 240 mL of blueberry juice
      (total polyphenols 300 mg and proanthocyanidin 76 mg/d) for 2 weeks. We analyzed
      8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) levels in their urine,
      and global and specific DNA methylation at the NAD(P)H quinone oxidoreductase 1
      (NQO1), methylenetetrahydrofolate reductase (MTHFR), or DNA methyltransferase 1
      (DNMT1) genes in their blood. RESULTS: Urinary 8-OHdG levels were reduced by
      blueberry consumption rather than by vitamin C. The methylation (%) of the MTHFR
      was significantly decreased in blueberry-consumers and the antioxidant
      susceptible subgroup, whose urinary MDA levels were decreased by the
      intervention. We also found a positive correlation between changes of urinary 8
      OHdG and of DNA methylation at the MTHFR or the DNMT1 (P < 0.05). However, the
      genetic polymorphism of the MTHFR (C677T in exon 4) did not affect any above
      markers. CONCLUSIONS: Blueberry juice shows similar anti-oxidative or anti
      premutagenic activity to vitamin C and the potential as a methylation inhibitor
      for the MTHFR and the DNMT1 in human.

PMID- 29018780
TI  - Comparison of Colonoscopy Surveillance Outcomes Between Young and Older
      Colorectal Cancer Patients.
AB  - BACKGROUND: Young-onset colorectal cancer is uncommon, but the incidence is
      increasing. Despite several guidelines for colonoscopic surveillance following
      colorectal cancer resection, there is little consistency regarding the timing and
      age-adjusted strategies of surveillance colonoscopy after surgery of young-onset
      colorectal cancer. The aim of this study was to compare the outcomes of
      surveillance colonoscopy between sporadic colorectal cancer patients with young
      and older age after curative resection. METHODS: We retrospectively reviewed 569
      colorectal cancer patients who underwent curative resection between January 2006
      and December 2010. The primary outcome was comparison of the development of
      metachronous advanced neoplasia during surveillance colonoscopy between young and
      older colorectal cancer patients. RESULTS: There were 95 patients in the young
      age group and 474 patients in the older age group. The mean time interval from
      surgery to the development of metachronous advanced neoplasia was 99.2 +/- 3.7
      months in the young age group and 84.4 +/- 2.5 months in the old age group (P =
      0.03). In the multivariate analysis, age (OR, 3.56; P = 0.04) and family history
      of colorectal cancer (OR, 2.66; P = 0.008) were associated with the development
      of metachronous advanced neoplasia. None of the young patients without both
      family history of colorectal cancer and high-risk findings at index colonoscopy
      showed advanced neoplasia during the follow-up period. CONCLUSIONS: Age and
      family history of colorectal cancer are independent risk factors for the
      occurrence of advanced neoplasia after curative colorectal cancer resection,
      suggesting age-adjusted strategies of surveillance colonoscopy.

PMID- 29018783
TI  - Effects of Erythrocyte Membrane Polyunsaturated Fatty Acids in Overweight, Obese,
      and Morbidly Obese Korean Women.
AB  - BACKGROUND: The levels of erythrocyte polyunsaturated fatty acids (FAs) may be
      associated with obesity, metabolic syndrome, and cancer. Thus, we investigated
      the association between erythrocyte n-3 and n-6 FA composition, body mass index
      (BMI), and biochemical profiles. METHODS: The body composition, dietary intake,
      and blood parameters, including serum lipid, glucose, insulin, adipokines,
      oxidative stress, and erythrocyte FA, were assessed in 66 overweight and obese
      women (average age, 43.4 years). We also classified the participants into the
      overweight, obese, and morbidly obese (MO) groups based on the BMI values of 23,
      25, and 30 kg/m2, respectively. Erythrocyte FA was measured via gas
      chromatography. RESULTS: The serum glucose, triglyceride, total cholesterol, and
      low-density lipoprotein cholesterol levels of the participants in the overweight,
      obese, and MO groups were not significantly different. However, the serum
      insulin, high-density lipoprotein, cholesterol and leptin levels were
      significantly different. The erythrocyte n-6/n-3 ratios of the overweight, obese,
      and MO groups were 2.4, 2.5, and 2.8, respectively. These data were consistent
      with the dietary n-6/n-3 ratio findings. Moreover, the erythrocyte n-6/n-3 ratio
      was correlated with serum insulin levels. CONCLUSIONS: As the severity of obesity
      increased, the levels of insulin and leptin and the ratio of dietary n-6/n-3
      increased, which was consistent with erythrocyte FA. These results indicate that
      erythrocyte FA may be a predictive biomarker for the increased prevalence of
      obesity, insulin resistance, leptin resistance, and risk of developing metabolic
      disorders.

PMID- 29018784
TI  - Peroxisome Proliferator-activated Receptor-gamma Inhibits the Activation of STAT3
      in Cerulein-stimulated Pancreatic Acinar Cells.
AB  - Cerulein-induced pancreatitis is similar to human edematous pancreatitis,
      characterized by the dysregulation of digestive enzyme production, edema
      formation, and an infiltration of inflammatory cells into the pancreas. We
      previously showed that the Janus kinase 2 (JAK2)/STAT3 pathway mediates
      inflammatory signaling in cerulein-stimulated pancreatic acinar cells. PPAR-gamma
      has been implicated in the regulation of inflammatory responses in several cells.
      In the present study, we investigated the role of PPAR-gamma in cerulein-induced
      activation of JAK2/STAT3 in pancreatic acinar cells. Treatment with cerulein
      induced the activation of JAK2/STAT3 and PPAR-gamma expression in AR42J cells.
      Cerulein-induced PPAR-gamma expression was inhibited by AG490, a JAK2/STAT3
      inhibitor, in AR42J cells. An immunoprecipitation analysis showed that PPAR-gamma
      binds to STAT3 in cerulein-stimulated AR42J cells. Down-regulation of PPAR-gamma
      by siRNA increased STAT3 phosphorylation in AR42J cells stimulated with cerulein.
      These results show that PPAR-gamma inactivates STAT3 by directly interacting with
      STAT3 in cerulein-stimulated pancreatic acinar cells. Overexpression of PPAR
      gamma may be beneficial for preventing pancreatitis by suppressing the activation
      of STAT3 in pancreatic acinar cells.

PMID- 29018785
TI  - Regulation of Inflammation by Sucrose Isomer, Turanose, in Raw 264.7 Cells.
AB  - Increased sugar consumption has been proposed to be a risk factor for obesity
      related metabolic disorders. The objective of this study was to investigate the
      anti-inflammatory effect of turanose in Raw 264.7 macrophages. Turanose (3-O
      alpha-D-glucosyl-D-fructose), an isomer of sucrose, naturally exists in honey.
      For these studies, macrophages were treated with total glucose (Glu), 50% Glu/50%
      turanose (T50), 25% Glu/75% turanose (T75), and 100% turanose (T100), each with a
      total concentration of 25 mM in cell media. Expressions of inflammatory enzymes
      and cytokines were analyzed. Cell viability was not affected in the turanose
      treated groups compared to the Glu group. Lipopolysaccharide and glucose-induced
      nitric oxide production, protein expression of inducible nitric oxide synthase,
      COX-2, and superoxide dismutase 2, and mRNA expression levels of interleukin (IL)
      1beta and IL-18 were significantly suppressed by turanose treatment. These
      results demonstrate that turanose exerts anti-inflammatory effects in vitro, and
      possesses potential to serve therapeutic functional sweetener for testing in vivo
      and in clinical trials.

PMID- 29018786
TI  - Hypoglossal nerve stimulation for treatment of obstructive sleep apnea (OSA): a
      primer for oral and maxillofacial surgeons.
AB  - The prevalence of obstructive sleep apnea (OSA) is estimated to be 1-5% of the
      adult population world-wide, and in Korea, it is reported at 4.5% of men and 3.2%
      of women (Age 40 to 69 years old). Active treatment of OSA is associated with
      decrease in insulin resistance, cardiovascular disease, psychosocial problems,
      and mortality. Surgical treatment of OSA has evolved in the era of
      neuromodulation with the advent of hypoglossal nerve stimulation (HGNS). We share
      this review of HGNS with our maxillofacial surgical colleagues to expand the
      scope of surgical care for OSA.

PMID- 29018788
TI  - Transition from Laparotomy to Laparoscopic Repair of Congenital Duodenal
      Obstruction in Neonates: Our Early Experience.
AB  - BACKGROUND: The aim of this report was to review our early experience of the last
      7 years with repairs of congenital duodenal obstruction (CDO) to determine the
      efficacy and outcomes of laparoscopic repairs compared to laparotomy. METHODS: A
      retrospective review was conducted on all neonate (<30 days) with CDO between
      2009 and 2015. Patients with duodenal atresia, stenosis, web, and annular
      pancreas were included. Patients with only malrotation or delayed presentation
      were excluded. RESULTS: Twenty-six neonates underwent laparoscopy and 30
      underwent traditional laparotomy. The operative time was longer in the
      laparoscopic group (P = 0.001), but time to initiation of feeds and time to full
      feeds were similar for the laparoscopic and open groups. There was no mortality,
      anastomosis leakage, or stenosis in the laparoscopic group. Six laparoscopic
      cases required conversion to an open procedure (23%). In the earlier cases, the
      open conversion rate was high, but it decreased over time (P = 0.003).
      CONCLUSION: Laparoscopic repair is safe and effective for repair of CDO in
      neonates. Despite operative time was slightly longer in the laparoscopic group,
      clinical outcomes remained similar to the open group. For pediatric surgeon with
      experience in laparoscopic techniques, laparoscopic duodenoduodenostomy is a
      sufficient available procedure.

PMID- 29018789
TI  - Cost-Effectiveness of a Family Planning Voucher Program in Rural Pakistan.
AB  - INTRODUCTION: This study reports on the effectiveness and efficiency from the
      program funder's perspective of the Suraj Social Franchise (SSF) voucher program
      in which private health-care providers in remote rural areas were identified,
      trained, upgraded, and certified to deliver family planning services to
      underserved women of reproductive age in 29 districts of Sindh and 3 districts of
      Punjab province, Pakistan between October 2013 and June 2016. METHOD: A decision
      tree compared the cost of implementing SSF to the program funder and its effects
      of providing additional couple years of protection (CYPs) to targeted women,
      compared to business-as-usual. Costs included vouchers given to women to receive
      a free contraceptive method of their choice from the SSF provider. The vouchers
      were then reimbursed to the SSF provider by the program. RESULTS: A total of
      168,206 married women of reproductive age (MWRA) received SSF vouchers between
      October 2013 and June 2016, costing $3,278,000 ($19.50/recipient). The average
      effectiveness of the program per voucher recipient was an additional 1.66 CYPs,
      giving an incremental cost-effectiveness of the program of $4.28 per CYP compared
      to not having the program (95% CI: $3.62-5.31). CONCLUSION: The result compares
      favorably to other interventions with similar objectives and appears affordable
      for the Pakistan national health-care system. It is therefore recommended to help
      address the unmet need for contraception among MWRA in these areas of Pakistan
      and is worthy of trial implementation in the country more widely.

PMID- 29018787
TI  - Cesarean Section, Formula Feeding, and Infant Antibiotic Exposure: Separate and
      Combined Impacts on Gut Microbial Changes in Later Infancy.
AB  - Established during infancy, our complex gut microbial community is shaped by
      medical interventions and societal preferences, such as cesarean section, formula
      feeding, and antibiotic use. We undertook this study to apply the significance
      analysis of microarrays (SAM) method to quantify changes in gut microbial
      composition during later infancy following the most common birth and postnatal
      exposures affecting infant gut microbial composition. Gut microbiota of 166 full
      term infants in the Canadian Healthy Infant Longitudinal Development birth cohort
      were profiled using 16S high-throughput gene sequencing. Infants were placed into
      groups according to mutually exclusive combinations of birth mode
      (vaginal/cesarean birth), breastfeeding status (yes/no), and antibiotic use
      (yes/no) by 3 months of age. Based on repeated permutations of data and
      adjustment for the false discovery rate, the SAM statistic identified
      statistically significant changes in gut microbial abundance between 3 months and
      1 year of age within each infant group. We observed well-known patterns of
      microbial phyla succession in later infancy (declining Proteobacteria; increasing
      Firmicutes and Bacteroidetes) following vaginal birth, breastfeeding, and no
      antibiotic exposure. Genus Lactobacillus, Roseburia, and Faecalibacterium species
      appeared in the top 10 increases to microbial abundance in these infants.
      Deviations from this pattern were evident among infants with other perinatal co
      exposures; notably, the largest number of microbial species with unchanged
      abundance was seen in gut microbiota following early cessation of breastfeeding
      in infants. With and without antibiotic exposure, the absence of a breast milk
      diet by 3 months of age following vaginal birth yielded a higher proportion of
      unchanged abundance of Bacteroidaceae and Enterobacteriaceae in later infancy,
      and a higher ratio of unchanged Enterobacteriaceae to Alcaligenaceae microbiota.
      Gut microbiota of infants born vaginally and exclusively formula fed became less
      enriched with family Veillonellaceae and Clostridiaceae, showed unchanging levels
      of Ruminococcaceae, and exhibited a greater decline in the
      Rikenellaceae/Bacteroidaceae ratio compared to their breastfed, vaginally
      delivered counterparts. These changes were also evident in cesarean-delivered
      infants to a lesser extent. The clinical relevance of these trajectories of
      microbial change is that they culminate in taxon-specific abundances in the gut
      microbiota of later infancy, which we and others have observed to be associated
      with food sensitization.

PMID- 29018790
TI  - Synergistic Effects of Unintended Pregnancy and Young Motherhood on Shaking and
      Smothering of Infants among Caregivers in Nagoya City, Japan.
AB  - BACKGROUND: Shaking and smothering in response to infant crying are forms of
      child abuse that often result in death. Unintended pregnancy and young motherhood
      are risk factors of such child maltreatment that are often comorbid, few studies
      have examined their synergistic effect on shaking and smothering of infants. We
      examined the synergistic effects of unintended pregnancy and young motherhood on
      shaking and smothering among caregivers of infants in Japan. METHODS: In this
      retrospective cohort study, a questionnaire was administered to caregivers
      enrolled for a health check for 3- to 4-month-old infants between October 2013
      and February 2014 in Nagoya City, Japan. The questionnaire data were linked to
      those from pregnancy notification forms registered at municipalities and included
      information on women's age and feelings about their pregnancy (N = 4,159). Data
      were analyzed using logistic regression analysis in 2016. RESULTS: Shaking and
      smothering of 3- to 4-month-old infants occurred at least once in the past month
      in 2.0 and 1.5% of cases, respectively. Of all participants, 24.8% reported
      unintended pregnancy while 7.3% were younger than 25 years old. Infants of young
      mothers (under 25 years old) with unintended pregnancy were 2.77 [95% confidence
      interval (CI): 1.15-6.68] and 5.61 (95% CI: 2.40-13.1) times more likely to be
      shaken and smothered, respectively, than those of older mothers with intended
      pregnancy. In addition, the odds ratio of young mothers with unintended pregnancy
      regarding smothering was significantly higher than that of older mothers with
      unintended pregnancy (odds ratio: 2.12; p = 0.02). CONCLUSION: Our findings
      suggest a synergistic effect of unintended pregnancy and young motherhood on
      smothering. Infants of young mothers with unintended pregnancy are at greater
      risk of abuse, especially smothering. Prevention strategies are required for
      young women with unintended pregnancies.

PMID- 29018791
TI  - A Novel Multiplayer Screen-Based Simulation Experience for African Learners
      Improved Confidence in Management of Postpartum Hemorrhage.
AB  - INTRODUCTION: Postpartum hemorrhage (PPH) remains a global challenge, affecting
      thirteen million women each year. In addition, PPH is a leading cause of maternal
      mortality in Asia and Africa. In the U.S.A., care of critically ill patients is
      often practiced using mannequin-based simulation. Mannequin-based simulation
      presents challenges in global health, particularly in low- or middle-income
      countries. We developed a novel multiplayer screen-based simulation in a virtual
      world enabling the practice of team coordination with PPH. We used this
      simulation with learners in Mulago, Uganda. We hypothesized that a multiplayer
      screen-based simulation experience would increase learner confidence in their
      ability to manage PPH. METHODS: The study design was a simple pre- and a post
      intervention survey. Forty-eight interprofessional subjects participated in one
      of nine 1-h simulation sessions using the PPH software. A fifteen-question self
      assessment administered before and after the intervention was designed to probe
      the areas of learning as defined by Bloom and Krathwohl: affective, cognitive,
      and psychomotor. RESULTS: Combined confidence scores increased significantly
      overall following the simulation experience and individually in each of the three
      categories of Bloom's Taxonomy: affective, cognitive, and psychomotor.
      CONCLUSION: We provide preliminary evidence that multiplayer screen-based
      simulation represents a scalable, distributable form of learning that may be used
      effectively in global health education and training. Interestingly, despite our
      intervention being screen-based, our subjects showed improved confidence in their
      ability to perform psychomotor tasks. Although there is precedent for mental
      rehearsal improving performance, further research is needed to understand this
      finding.

PMID- 29018792
TI  - Editorial: Evidence-Based Public Health: Why, What and How.

PMID- 29018793
TI  - The Risk of Hypertension and Other Chronic Diseases: Comparing Smokeless Tobacco
      with Smoking.
AB  - BACKGROUND: In the past, studies have compared smokeless tobacco and non-tobacco
      users for the risk of various chronic diseases. The differences in the risk of
      chronic diseases between smokeless tobacco user and smokers have not been
      explored. The objective of this study is to estimate the risk of chronic diseases
      among smokeless tobacco users compared to smokers. METHODS: The data were used
      from the Study on Global Ageing and Adult Health (SAGE) Wave-1, conducted in 2007
      2008 in India. The study sample is the respondents who reported consuming any
      form of tobacco in last 1 month. The total sample size was 4,038 respondents. The
      odds ratio of chronic morbidities was estimated taking smokers as the reference
      category. RESULTS: The odds ratios for (self-reported) diabetes, asthma, and
      hypertension were not significant for smokeless tobacco user compared to smoked
      tobacco users. The odds ratio of chronic lung diseases (CLDs) was significantly
      lower among smokeless tobacco users compared to smoked tobacco users. The odds
      ratio of hypertension (measured) combined with low education and belonging to
      lowest wealth quintiles were not significant for smokeless tobacco users compared
      to smoked tobacco users. Duration of the use of smokeless tobacco and quantity of
      use was found to have no significant relation with risk of chronic diseases as
      compared to smoking. CONCLUSION: This study did not find the significantly higher
      risk of chronic morbidities except for CLD for smokeless tobacco users compared
      to smoked tobacco users. The study suggests that the use of any form of tobacco
      may have a similar risk of chronic diseases.

PMID- 29018794
TI  - Synergistic Catalysis by "Polymeric Microzymes and Inorganic Nanozymes": The
      1+1>2 Effect for Intramolecular Cyclization of Peptides.
AB  - In this work, we developed an efficient "molecularly imprinted polymer microzymes
      and inorganic magnetic nanozymes" synergistic catalysis strategy for the
      formation of disulfide bonds in peptides. The polymeric microzymes showed
      excellent selectivity toward the template peptide as well as the main reactant
      (linear peptide), and the Fe3O4 magnetic nanoparticle (MNP) nanozymes inhibited
      the intermolecular reaction during the formation of disulfide bonds in peptides.
      As a result, the integration of the two different artificial enzymes in one
      process facilitates the intramolecular cyclization in high product yields (59.3%)
      with excellent selectivity. Mechanism study indicates the synergistic effect was
      occurred by using a "reversed solid phase synthesis" strategy with an enhanced
      shift of reaction balance to product generation. We believe the synergistic
      catalysis by "polymeric microzymes and inorganic nanozymes" presented in the
      present work may open new opportunities in creation of multifunctional enzyme
      mimics for sensing, imaging, and drug delivery.

PMID- 29018795
TI  - Poly(Ionic Liquid) Based Chemosensors for Detection of Basic Amino Acids in
      Aqueous Medium.
AB  - Naked-eye detection of amino acids (AA) in water is of great significance in the
      field of bioanalytical applications. Herein, polymerized ionic liquids (PILs)
      with controlled chain length structures were synthesized via reversible addition
      fragmentation chain-transfer (RAFT) polymerization and post-quaternization
      approach. The AA recognition performance of PILs with different alkyl chain
      lengths and molecular weights was evaluated by naked-eye color change and
      ultraviolet-visible (UV-vis) spectral studies. These PILs were successfully used
      for highly sensitive and selective detection of Arg, Lys, and His in water. The
      recognition performance was improved effectively with increased molecular weight
      of PILs. The biosensitivity of the PILs in water was strongly dependent on their
      aggregation effect and polarization effect. Highly sensitive and selective
      detection of AA was successfully accomplished by introducing positively charged
      pyridinium moieties and controlled RAFT radical polymerization.

PMID- 29018796
TI  - Novel Carbonyl Analogs of Tamoxifen: Design, Synthesis, and Biological
      Evaluation.
AB  - Aim of this work was to provide tamoxifen analogs with enhanced estrogen receptor
      (ER) binding affinity. Hence, several derivatives were prepared using an
      efficient triarylethylenes synthetic protocol. The novel compounds bioactivity
      was evaluated through the determination of their receptor binding affinity and
      their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell
      based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both
      ERalpha and ERbeta higher than 4-hydroxytamoxifen while compounds 13 and 14 have
      shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the
      known ER inhibitor ICI182,780. Theoretical calculations and molecular modeling
      were applied to investigate, support and explain the biological profile of the
      new compounds. The relevant data indicated an agreement between calculations and
      demonstrated biological activity allowing to extract useful structure-activity
      relationships. Results herein underline that modifications of tamoxifen structure
      still provide molecules with substantial activity, as portrayed in the inhibition
      of MCF-7 cells proliferation.

PMID- 29018798
TI  - TAFRO Syndrome in Caucasians: A Case Report and Review of the Literature.
AB  - BACKGROUND: TAFRO syndrome has been reported in Japan among human herpesvirus 8
      (HHV-8)-negative/idiopathic multicentric Castleman's disease (iMCD) patients. To
      date, the majority of iMCD patients with TAFRO syndrome originate from Japan.
      CASE PRESENTATION: Herein, we report a 67-year-old HIV/HHV-8-negative Caucasian
      iMCD patient diagnosed with TAFRO. He presented with marked systemic
      inflammation, bicytopenia, terminal renal insufficiency, diffuse
      lymphadenopathies, and anasarca. Lymph node and bone marrow biopsies revealed
      atrophic germinal centers variably hyalinized and megakaryocytic hyperplasia with
      mild myelofibrosis. Several other biopsies performed in kidneys, liver,
      gastrointestinal tract, prostate, and lungs revealed unspecific chronic
      inflammation. The patient had a complete response to corticosteroids,
      tocilizumab, and rituximab. He relapsed twice following discontinuation of
      rituximab. When reviewing the literature, we found seven other Caucasian cases
      with TAFRO syndrome. There were no significant differences with those described
      by the Japanese cohort except for the higher frequency of kidney failure and auto
      antibodies in Western patients. CONCLUSION: This case illustrates that patients
      with TAFRO syndrome can develop non-specific inflammation in several tissue
      sites. Furthermore, this case and our review of the literature demonstrate that
      TAFRO syndrome can affect Caucasian and Japanese patients highlighting the
      importance of evaluating for this syndrome independently of ethnic background.

PMID- 29018799
TI  - TruSeq-Based Gene Expression Analysis of Formalin-Fixed Paraffin-Embedded (FFPE)
      Cutaneous T-Cell Lymphoma Samples: Subgroup Analysis Results and Elucidation of
      Biases from FFPE Sample Processing on the TruSeq Platform.
AB  - Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of malignancies with
      courses ranging from indolent to potentially lethal. We recently studied in a 157
      patient cohort gene expression profiles generated by the TruSeq targeted RNA gene
      expression sequencing. We observed that the sequencing library quality and depth
      from formalin-fixed paraffin-embedded (FFPE) skin samples were significantly
      lower when biopsies were obtained prior to 2009. We also observed that the fresh
      CTCL samples clustered together, even though they included stage I-IV disease. In
      this study, we compared TruSeq gene expression patterns in older (<=2008) vs.
      more recent (>=2009) FFPE samples to determine whether these clustering analyses
      and earlier described differentially expressed gene findings are robust when
      analyzed based on the year of biopsy. We also explored biases found in FFPE
      samples when subjected to the TruSeq analysis of gene expression. Our results
      showed that <=2008 and >=2009 samples clustered equally well to the full data set
      and, importantly, both analyses produced nearly identical trends and findings.
      Specifically, both analyses enriched nearly identical DEGs when comparing benign
      vs. (1) stage I-IV and (2) stage IV (alone) CTCL samples. Results obtained using
      either <=2008 or >=2009 samples were strongly correlated. Furthermore, by using
      subgroup analyses, we were able to identify additional novel differentially
      expressed genes (DEGs), which did not reach statistical significance in the prior
      full data set analysis. Those included CTCL-upregulated BCL11A, SELL, IRF1,
      SMAD1, CASP1, BIRC5, and MAX and CTCL-downregulated MDM4, SERPINB3, and THBS4
      genes. With respect to sample biases, no matter if we performed subgroup analyses
      or full data set analysis, fresh samples tightly clustered together. While
      principal component analysis revealed that fresh samples were spatially closer
      together, indicating some preprocessing batch effect, they remained in the
      proximity to other normal/benign and FFPE CTCL samples and were not clustering as
      outliers by themselves. Notably, this did not affect the determination of DEGs
      when analyzing >=2009 samples (fresh and FFPE biopsies) vs. >=2009 FFPE samples
      alone.

PMID- 29018801
TI  - Editorial: Factors Promoting Development of Fibrosis in Crohn's Disease.

PMID- 29018800
TI  - Asthma Endotypes and an Overview of Targeted Therapy for Asthma.
AB  - Guidelines for the management of severe asthma do not emphasize the measurement
      of the inflammatory component of airway disease to indicate appropriate
      treatments or to monitor response to treatment. Inflammation is a central
      component of asthma and contributes to symptoms, physiological, and structural
      abnormalities. It can be assessed by a number of endotyping strategies based on
      "omics" technology such as proteomics, transcriptomics, and metabolomics. It can
      also be assessed using simple cellular responses by quantitative cytometry in
      sputum. Bronchitis may be eosinophilic, neutrophilic, mixed-granulocytic, or
      paucigranulocytic (eosinophils and neutrophils not elevated). Eosinophilic
      bronchitis is usually a Type 2 (T2)-driven process and therefore a sputum
      eosinophilia of greater than 3% usually indicates a response to treatment with
      corticosteroids or novel therapies directed against T2 cytokines such as IL-4, IL
      5, and IL-13. Neutrophilic bronchitis represents a non-T2-driven disease, which
      is generally a predictor of response to antibiotics and may be a predictor to
      therapies targeted at pathways that lead to neutrophil recruitment such as TNF,
      IL-1, IL-6, IL-8, IL-23, and IL-17. Paucigranulocytic disease may not warrant
      anti-inflammatory therapy. These patients, whose symptoms may be driven largely
      by airway hyper-responsiveness may benefit from smooth muscle-directed therapies
      such as bronchial thermoplasty or mast-cell directed therapies. This review will
      briefly summarize the current knowledge regarding "omics-based signatures" and
      cellular endotyping of severe asthma and give an overview of segmentation of
      asthma therapeutics guided by the endotype.

PMID- 29018802
TI  - Corrigendum: Effect of Underlying Renal Disease on Nutritional and Metabolic
      Profile of Older Adults with Reduced Renal Function.
AB  - [This corrects the article on p. 4 in vol. 4, PMID: 28367435.].

PMID- 29018797
TI  - microRNAs Make the Call in Cancer Personalized Medicine.
AB  - Since their discovery and the advent of RNA interference, microRNAs have drawn
      enormous attention because of their ubiquitous involvement in cellular pathways
      from life to death, from metabolism to communication. It is also widely accepted
      that they possess an undeniable role in cancer both as tumor suppressors and
      tumor promoters modulating cell proliferation and migration, epithelial
      mesenchymal transition and tumor cell invasion and metastasis. Moreover,
      microRNAs can even affect the tumor surrounding environment influencing
      angiogenesis and immune system activation and recruitment. The tight association
      of microRNAs with several cancer-related processes makes them undoubtedly
      connected to the effect of specific cancer drugs inducing either resistance or
      sensitization. In this context, personalized medicine through microRNAs arose
      recently with the discovery of single nucleotide polymorphisms in the target
      binding sites, in the sequence of the microRNA itself or in microRNA biogenesis
      related genes, increasing risk, susceptibility and progression of multiple types
      of cancer in different sets of the population. The depicted scenario implies that
      the overall variation displayed by these small non-coding RNAs have an impact on
      patient-specific pharmacokinetics and pharmacodynamics of cancer drugs, pushing
      on a rising need of personalized treatment. Indeed, microRNAs from either tissues
      or liquid biopsies are also extensively studied as valuable biomarkers for
      disease early recognition, progression and prognosis. Despite microRNAs being
      intensively studied in recent years, a comprehensive review describing these
      topics all in one is missing. Here we report an up-to-date and critical summary
      of microRNAs as tools for better understanding personalized cancer biogenesis,
      evolution, diagnosis and treatment.

PMID- 29018804
TI  - Editorial: The Developments of Hybrid Surgical Strategies for Congenital Heart
      Disease.

PMID- 29018803
TI  - Etiology of Inguinal Hernias: A Comprehensive Review.
AB  - BACKGROUND: The etiology of inguinal hernias remains uncertain even though the
      lifetime risk of developing an inguinal hernia is 27% for men and 3% for women.
      The aim was to summarize the evidence on hernia etiology, with focus on
      differences between lateral and medial hernias. RESULTS: Lateral and medial
      hernias seem to have common as well as different etiologies. A patent processus
      vaginalis and increased cumulative mechanical exposure are risk factors for
      lateral hernias. Patients with medial hernias seem to have a more profoundly
      altered connective tissue architecture and homeostasis compared with patients
      with lateral hernias. However, connective tissue alteration may play a role in
      development of both subtypes. Inguinal hernias have a hereditary component with a
      complex inheritance pattern, and inguinal hernia susceptible genes have been
      identified that also are involved in connective tissue homeostasis. CONCLUSION:
      The etiology of lateral and medial hernias are at least partly different, but the
      final explanations are still lacking on certain areas. Further investigations of
      inguinal hernia genes may explain the altered connective tissue observed in
      patients with inguinal hernias. The precise mechanisms why processus vaginalis
      fails to obliterate in certain patients should also be clarified. Not all
      patients with a patent processus vaginalis develop a lateral hernia, but
      increased intraabdominal pressure appears to be a contributing factor.

PMID- 29018805
TI  - Insight into the Selectivity of the G7-18NATE Inhibitor Peptide for the Grb7-SH2
      Domain Target.
AB  - Growth factor receptor bound protein 7 (Grb7) is an adaptor protein with
      established roles in the progression of both breast and pancreatic cancers.
      Through its C-terminal SH2 domain, Grb7 binds to phosphorylated tyrosine kinases
      to promote proliferative and migratory signaling. Here, we investigated the
      molecular basis for the specificity of a Grb7 SH2-domain targeted peptide
      inhibitor. We identified that arginine 462 in the BC loop is unique to Grb7
      compared to Grb2, another SH2 domain bearing protein that shares the same
      consensus binding motif as Grb7. Using surface plasmon resonance we demonstrated
      that Grb7-SH2 binding to G7-18NATE is reduced 3.3-fold when the arginine is
      mutated to the corresponding Grb2 amino acid. The reverse mutation in Grb2-SH2
      (serine to arginine), however, was insufficient to restore binding of G7-18NATE
      to Grb2-SH2. Further, using a microarray, we confirmed that G7-18NATE is specific
      for Grb7 over a panel of 79 SH2 domains, and identified that leucine at the
      betaD6 position may also be a requirement for Grb7-SH2 binding. This study
      provides insight into the specificity defining features of Grb7 for the inhibitor
      molecule G7-18NATE, that will assist in the development of improved Grb7 targeted
      inhibitors.

PMID- 29018806
TI  - A Simple PB/LIE Free Energy Function Accurately Predicts the Peptide Binding
      Specificity of the Tiam1 PDZ Domain.
AB  - PDZ domains generally bind short amino acid sequences at the C-terminus of target
      proteins, and short peptides can be used as inhibitors or model ligands. Here, we
      used experimental binding assays and molecular dynamics simulations to
      characterize 51 complexes involving the Tiam1 PDZ domain and to test the
      performance of a semi-empirical free energy function. The free energy function
      combined a Poisson-Boltzmann (PB) continuum electrostatic term, a van der Waals
      interaction energy, and a surface area term. Each term was empirically weighted,
      giving a Linear Interaction Energy or "PB/LIE" free energy. The model yielded a
      mean unsigned deviation of 0.43 kcal/mol and a Pearson correlation of 0.64
      between experimental and computed free energies, which was superior to a Null
      model that assumes all complexes have the same affinity. Analyses of the models
      support several experimental observations that indicate the orientation of the
      alpha2 helix is a critical determinant for peptide specificity. The models were
      also used to predict binding free energies for nine new variants, corresponding
      to point mutants of the Syndecan1 and Caspr4 peptides. The predictions did not
      reveal improved binding; however, they suggest that an unnatural amino acid could
      be used to increase protease resistance and peptide lifetimes in vivo. The
      overall performance of the model should allow its use in the design of new PDZ
      ligands in the future.

PMID- 29018807
TI  - Listeria Occurrence in Poultry Flocks: Detection and Potential Implications.
AB  - Foodborne pathogens such as Salmonella, Campylobacter, Escherichia coli, and
      Listeria are a major concern within the food industry due to their pathogenic
      potential to cause infection. Of these, Listeria monocytogenes, possesses a high
      mortality rate (approximately 20%) and is considered one of the most dangerous
      foodborne pathogens. Although the usual reservoirs for Listeria transmission have
      been extensively studied, little is known about the relationship between Listeria
      and live poultry production. Sporadic and isolated cases of listeriosis have been
      attributed to poultry production and Listeria spp. have been isolated from all
      stages of poultry production and processing. Farm studies suggest that live birds
      may be an important vector and contributor to contamination of the processing
      environment and transmission of Listeria to consumers. Therefore, the purpose of
      this review is to highlight the occurrence, incidence, and potential systemic
      interactions of Listeria spp. with poultry.

PMID- 29018808
TI  - Tenogenically Induced Allogeneic Peripheral Blood Mesenchymal Stem Cells in
      Allogeneic Platelet-Rich Plasma: 2-Year Follow-up after Tendon or Ligament
      Treatment in Horses.
AB  - Poor healing of tendon and ligament lesions often results in early retirement of
      sport horses. Therefore, regenerative therapies are being explored as potentially
      promising treatment for these injuries. In this study, an intralesional injection
      was performed with allogeneic tenogenically induced mesenchymal stem cells and
      platelet-rich plasma 5-6 days after diagnosis of suspensory ligament (SL) (n =
      68) or superficial digital flexor tendon (SDFT) (n = 36) lesion. Clinical,
      lameness and ultrasonographic evaluation was performed at 6 and 12 weeks.
      Moreover, a survey was performed 12 and 24 months after treatment to determine
      how many horses were competing at original level and how many were re-injured. At
      6 weeks, 88.2% of SL (n = 68) and 97.3% of SDFT lesions (n = 36) demonstrated
      moderate ultrasonographic improvement. At 12 weeks, 93.1% of SL (n = 29) and
      95.5% of SDFT lesions (n = 22) improved convincingly. Moreover, lameness was
      abolished in 78.6% of SL (n = 28) and 85.7% (n = 7) of SDFT horses at 12 weeks.
      After 12 months (n = 92), 11.8% of SL and 12.5% of SDFT horses were re-injured,
      whereas 83.8 of SL and 79.2% of SDFT returned to previous performance level. At
      24 months (n = 89) after treatment, 82.4 (SL) and 85.7% (SDFT) of the horses
      returned to previous level of performance. A meta-analysis was performed on
      relevant published evidence evaluating re-injury 24 months after stem cell-based
      [17.6% of the SL and 14.3% of the SDFT group (n = 89)] versus conventional
      therapies. Cell therapies resulted in a significantly lower re-injury rate of 18%
      [95% confidence interval (CI), 0.11-0.25] 2 years after treatment compared to the
      44% re-injury rate with conventional treatments (95% CI, 0.37-0.51) based on
      literature data (P < 0.0001).

PMID- 29018809
TI  - Growth Factor-Reinforced ECM Fabricated from Chemically Hypoxic MSC Sheet with
      Improved In Vivo Wound Repair Activity.
AB  - MSC treatment can promote cutaneous wound repair through multiple mechanisms, and
      paracrine mediators secreted by MSC are responsible for most of its therapeutic
      benefits. Recently, MSC sheet composed of live MSCs and their secreted ECMs was
      reported to promote wound healing; however, whether its ECM alone could
      accelerate wound closure remained unknown. In this study, Nc-ECM and Cc-ECM were
      prepared from nonconditioned and CoCl2-conditioned MSC sheets, respectively, and
      their wound healing properties were evaluated in a mouse model of full-thickness
      skin defect. Our results showed that Nc-ECM can significantly promote wound
      repair through early adipocyte recruitment, rapid reepithelialization, enhanced
      granulation tissue growth, and augmented angiogenesis. Moreover, conditioning of
      MSC sheet with CoCl2 dramatically enriched its ECM with collagen I, collagen III,
      TGF-beta1, VEGF, and bFGF via activation of HIF-1alpha and hence remarkably
      improved its ECM's in vivo wound healing potency. All the Cc-ECM-treated wounds
      completely healed on day 7, while Nc-ECM-treated wounds healed about 85.0% +/-
      8.6%, and no-treatment wounds only healed 69.8% +/- 9.6% (p < 0.05). Therefore,
      we believe that such growth factor-reinforced ECM fabricated from chemically
      hypoxic MSC sheet has the potential for clinical translation and will lead to a
      MSC-derived, cost-effective, bankable biomaterial for wound management.

PMID- 29018810
TI  - Renaissance of Conventional First-Line Antibiotics in Salmonella enterica
      Clinical Isolates: Assessment of MICs for Therapeutic Antimicrobials in Enteric
      Fever Cases from Nepal.
AB  - Enteric fever caused by Salmonella enterica is a life-threatening systemic
      illness of gastrointestinal tract especially in tropical countries. Antimicrobial
      therapy is generally indicated but resistance towards commonly used antibiotics
      has limited their therapeutic usefulness. Therefore, we aimed to determine the
      antimicrobial susceptibility pattern by minimum inhibitory concentration method
      of common therapeutic regimens against Salmonella enterica from enteric fever
      clinical cases. Salmonella enterica clinical isolates recovered from the patients
      with suspected enteric fever whose blood samples were submitted to microbiology
      laboratory of Manmohan Memorial Community Hospital, Kathmandu, from March 2016 to
      August 2016, were studied. These isolates were subjected to antimicrobial
      susceptibility testing against common therapeutic antimicrobials by Kirby-Bauer
      disk diffusion method. The minimum inhibitory concentration of ciprofloxacin,
      azithromycin, chloramphenicol, and cefixime was determined by Agar dilution
      method based on the latest CLSI protocol. A total of 88 isolates of Salmonella
      enterica were recovered from blood samples of enteric fever cases. Out of them,
      74 (84.09%) were Salmonella Typhi and 14 (15.91%) were Salmonella Paratyphi A. On
      Kirby-Bauer disk diffusion antimicrobial susceptibility testing, entire isolates
      were susceptible to cotrimoxazole, cefixime, ceftriaxone, azithromycin, and
      chloramphenicol. Sixty-four (72.7%) Salmonella enterica isolates were nalidixic
      acid resistant and nonsusceptible to ciprofloxacin and levofloxacin. On MIC
      determination, four Salmonella isolates were ciprofloxacin resistant with MIC 1
      ug/ml and two isolates were ciprofloxacin intermediate with MIC 0.5 ug/ml. The
      MIC range of azithromycin was from 0.125 ug/ml to 2.0 ug/ml, whereas that for
      chloramphenicol was 2.0 ug/ml-8.0 ug/ml and for cefixime was 0.0075-0.5 ug/ml,
      respectively. Despite global surge of antimicrobial resistance among Salmonella
      enterica clinical isolates, the level of drug resistance in our study was not so
      high. However, higher level of NARST strains limits therapeutic use of
      fluoroquinolones and necessitates the routine monitoring of such resistance
      determinants in order to effectively and rationally manage enteric fever cases.

PMID- 29018811
TI  - High-Frequency EEG Variations in Children with Autism Spectrum Disorder during
      Human Faces Visualization.
AB  - Autism spectrum disorder (ASD) is a neuropsychiatric disorder characterized by
      the impairment in the social reciprocity, interaction/language, and behavior,
      with stereotypes and signs of sensory function deficits. Electroencephalography
      (EEG) is a well-established and noninvasive tool for neurophysiological
      characterization and monitoring of the brain electrical activity, able to
      identify abnormalities related to frequency range, connectivity, and
      lateralization of brain functions. This research aims to evidence quantitative
      differences in the frequency spectrum pattern between EEG signals of children
      with and without ASD during visualization of human faces in three different
      expressions: neutral, happy, and angry. Quantitative clinical evaluations,
      neuropsychological evaluation, and EEG of children with and without ASD were
      analyzed paired by age and gender. The results showed stronger activation in
      higher frequencies (above 30 Hz) in frontal, central, parietal, and occipital
      regions in the ASD group. This pattern of activation may correlate with
      developmental characteristics in the children with ASD.

PMID- 29018813
TI  - Cardiovascular Consequences of Repetitive Arousals over the Entire Sleep
      Duration.
AB  - OBJECTIVES: To explore the cardiovascular effects of nightlong repetitive
      arousals (RA). METHODS: Twenty healthy subjects participated in two consecutive
      sleep studies. The first one was free of intervention and the second study
      involved repetitive arousals induced by acoustical stimuli. Blood pressure, heart
      rate variability (HRV), arterial stiffness index (ASI), and serum markers
      including nitric oxide (NO), endothelin-1 (ET-1), C-reactive protein (CRP),
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and vascular
      endothelial growth factor (VEGF) were studied. RESULTS: RA led to overnight
      elevation in diastolic blood pressure (DBP) but not in systolic blood pressure
      (SBP). Regarding HRV, overnight increase in low frequency power (LF) and low
      frequency to high frequency ratio (LHR) and decrease in high frequency power (HF)
      were evident. The relative overnight differences in HF and LHR correlated with
      the amount of rapid-eye movement (REM) sleep. RA did not cause detectable change
      in either ASI or serum markers of interest. CONCLUSIONS: Nightlong RA alters the
      sympathovagal modulation significantly and this effect seems to be associated
      with the amount of REM sleep. Exposure to RA also causes an elevation in
      postsleep DBP. Disturbance to autonomic nervous system (ANS) may precede
      endothelial dysfunction and increased arterial stiffness as cardiovascular
      consequences of RA.

PMID- 29018812
TI  - Abeta Peptide Originated from Platelets Promises New Strategy in Anti-Alzheimer's
      Drug Development.
AB  - The amyloid beta (Abeta) peptide and its deposits in the brain are known to be
      implicated in the neurodegeneration that occurs during Alzheimer's disease (AD).
      Recently, alternative theories views concerning both the source of this peptide
      and its functions have been developed. It has been shown that, as in all other
      known types of amyloidosis, the production of Abeta originates in blood cells or
      cells related to blood plasma, from which it can then spread from the blood to
      inside the brain, with the greatest concentration around brain blood vessels. In
      this review, we summarize research progress in this new area and outline some
      future perspectives. While it is still unclear whether the main source of Abeta
      deposits in AD is the blood, the possibility of blocking the chain of reactions
      that lead to constant Abeta release from the blood to the brain may be exploited
      in an attempt to reduce the amyloid burden in AD. Solving the problem of Abeta
      accumulation in this way may provide an alternative strategy for developing anti
      AD drugs.

PMID- 29018815
TI  - Effect of Free Ammonia, Free Nitrous Acid, and Alkalinity on the Partial
      Nitrification of Pretreated Pig Slurry, Using an Alternating Oxic/Anoxic SBR.
AB  - The effect of free ammonia (NH3 or FA), free nitrous acid (HNO2 or FNA), and
      total alkalinity (TA) on the performance of a partial nitrification (PN)
      sequencing batch reactor (SBR) treating anaerobically pretreated pig slurry was
      studied. The SBR was operated under alternating oxic/anoxic (O/A) conditions and
      was fed during anoxic phases. This strategy allowed using organic matter to
      partially remove nitrite (NO2-) and nitrate (NO3-) generated during oxic phases.
      The desired NH4+ to NO2- ratio of 1.3 g N/g N was obtained when an Ammonium
      Loading Rate (ALR) of 0.09 g NH4+-N/L.d was applied. The system was operated at a
      solid retention time (SRT) of 15-20 d and dissolved oxygen (DO) levels higher
      than 3 mg O2/L during the whole operational period. PN mainly occurred caused by
      the inhibitory effect of FNA on nitrite oxidizing bacteria (NOB). Once HNO2
      concentration was negligible, NH4+ was fully oxidized to NO3- in spite of the
      presence of FA. The use of biomass acclimated to ammonium as inoculum avoided a
      possible effect of FA on NOB activity.

PMID- 29018814
TI  - The Impact of Frailty on Morbidity and Mortality following Open Emergent
      Colectomies.
AB  - BACKGROUND: Elderly and frail patients undergo open emergency colectomies and are
      at greater risk for complications. The relationship between frailty and open
      emergent colectomies is yet unexplored. OBJECTIVE: The purpose of this study was
      to evaluate the relationship between frailty and outcomes after open emergent
      colorectal surgery. DESIGN: Using the American College of Surgeons National
      Quality Improvement Program database, a validated modified frailty index was
      used, along with logistic regression, to assess the relationship between frailty
      and outcomes. MAIN OUTCOME MEASURES: Outcomes included mortality (primary),
      Clavien-Dindo Complication Grade >3, reintubation, ventilator >48 hours, and
      reoperation (secondary). RESULTS: The rates for 30-day mortality, Clavien-Dindo
      Grade >3, reintubation, ventilator > 48 hours, and reoperation in our cohort were
      16.6%, 36.9%, 8.6%, 23.9%, and 15.0%, respectively. There was a statistically
      significant increase in prevalence of all outcomes with increasing frailty.
      LIMITATIONS: A causal relationship between frailty and complications cannot be
      established in a retrospective analysis. Also, extrapolation of our data to
      reflect outcomes beyond 30 days must be done with caution. CONCLUSIONS: Frailty
      is a statistically significant predictor of mortality and morbidity after open
      emergent colectomies and can be used in an acute care setting.

PMID- 29018817
TI  - Balance Performance Is Task Specific in Older Adults.
AB  - Balance ability among the elderly is a key component in the activities of daily
      living and is divided into two types: static and dynamic. For clinicians who wish
      to assess the risk of falling among their elderly patients, it is unclear if more
      than one type of balance test can be used to measure their balance impairment. In
      this study, we examined the association between static balance measures and two
      dynamic balance field tests. One hundred and twelve community-dwelling older
      adults (mean age 74.6) participated in the study. They underwent the Tetrax
      static postural assessment and then performed the Timed Up and Go (TUG) and the
      Functional Reach (FR) Test as dynamic balance tests. In general, low-moderate
      correlations were found between the two types of balance tests. For women, age
      and static balance parameters explained 28.1-40.4% of the variance of TUG scores
      and 14.6-24% of the variance of FR scores. For men, age and static balance
      parameters explained 9.5-31.2% of the variance of TUG scores and 23.9-41.7% of
      the variance of FR scores. Based on our findings, it is suggested that a
      combination of both static and dynamic tests be used for assessing postural
      balance ability.

PMID- 29018816
TI  - Comparative Evaluation between Sulfasalazine Alone and in Combination with Herbal
      Medicine on DSS-Induced Ulcerative Colitis Mice.
AB  - The present study aimed to investigate the comparative evaluation of
      pharmacological efficacy between sulfasalazine alone and sulfasalazine in
      combination with herbal medicine on dextran sodium sulfate- (DSS-) induced UC in
      mice. Balb/c mice received 5% DSS in drinking water for 7 days to induce colitis.
      Animals were divided into five groups (n = 9): Group I (normal group), Group II
      (DSS control group), Group III (DSS + sulfasalazine (30 mg/kg)), Group IV (DSS +
      sulfasalazine (60 mg/kg)), and Group V (DSS + sulfasalazine (30 mg/kg) +
      Cinnamomi Cortex and Bupleuri Radix mixture (30 mg/kg) (SCB)). Colonic
      pathological changes were analyzed using hematoxyline/eosin staining. The
      antioxidant, inflammatory, and apoptotic protein levels were determined using
      western blotting. SCB supplementation, as well as sulfasalazine, suppressed
      colonic length and mucosal inflammatory infiltration. In addition, SCB treatment
      significantly reduced the expression of proinflammatory signaling molecules
      through suppression of both mitogen-activated protein kinases (MAPK) and nuclear
      factor-kappa B (NF-kappaB) signaling pathways and prevented the apoptosis of the
      colon. Moreover, SCB administration significantly led to the upregulation of
      antioxidant enzymes including SOD and catalase. Taken together, SCB treatment
      might offer a better treatment for human UC than sulfasalazine alone or may be
      useful as an alternative therapeutic strategy against UC, without any evidence of
      side effects.

PMID- 29018818
TI  - The Mechanical Properties and Biometrical Effect of 3D Preformed Titanium
      Membrane for Guided Bone Regeneration on Alveolar Bone Defect.
AB  - The purpose of this study is to evaluate the effect of three-dimensional
      preformed titanium membrane (3D-PFTM) to enhance mechanical properties and
      ability of bone regeneration on the peri-implant bone defect. 3D-PFTMs by new
      mechanically compressive molding technology and manually shaped- (MS-) PFTMs by
      hand manipulation were applied in artificial peri-implant bone defect model for
      static compressive load test and cyclic fatigue load test. In 12 implants
      installed in the mandibular of three beagle dogs, six 3D-PFTMs, and six collagen
      membranes (CM) randomly were applied to 2.5 mm peri-implant buccal bone defect
      with particulate bone graft materials for guided bone regeneration (GBR). The 3D
      PFTM group showed about 7.4 times higher mechanical stiffness and 5 times higher
      fatigue resistance than the MS-PFTM group. The levels of the new bone area (NBA,
      %), the bone-to-implant contact (BIC, %), distance from the new bone to the old
      bone (NB-OB, %), and distance from the osseointegration to the old bone (OI-OB,
      %) were significantly higher in the 3D-PFTM group than the CM group (p < .001).
      It was verified that the 3D-PFTM increased mechanical properties which were
      effective in supporting the space maintenance ability and stabilizing the
      particulate bone grafts, which led to highly efficient bone regeneration.

PMID- 29018819
TI  - The Clinical Significance of FilmArray Respiratory Panel in Diagnosing Community
      Acquired Pneumonia.
AB  - AIM: FilmArray Respiratory Panel (FilmArray RP) test is an emerging diagnostic
      method in fast detecting multiple respiratory pathogens; the methodology and
      clinical significance of FilmArray RP in community-acquired pneumonia (CAP)
      diagnosis were evaluated in this study. METHODS: Specimens from 74 patients with
      CAP were analyzed and compared using FilmArray RP, traditional multiple PCR
      assay, bacterial (or fungal) culture, and serological detection. RESULTS:
      FilmArray RP and multiplex PCR showed 100% coincidence rate in detecting
      coronaviruses 229E, OC43, HKU1, and NL63, human metapneumovirus, influenza A and
      B, and parainfluenza viruses (PIV1, PIV2, and PIV4). There were 15 viral
      specimens tested as disagreement positive results. FilmArray RP had higher
      detection rate in detecting dual viral and Mycoplasma pneumoniae infection. The
      positive bacteria (or fungi) were found in 25 specimens. CONCLUSIONS: This study
      demonstrated the capability of FilmArray RP for simultaneous detection of broad
      spectrum respiratory pathogens and potential use in facilitating better patient
      care.

PMID- 29018820
TI  - The Effect of LASIK Procedure on Peripapillary Retinal Nerve Fiber Layer and
      Macular Ganglion Cell-Inner Plexiform Layer Thickness in Myopic Eyes.
AB  - PURPOSE: To evaluate the effect of applied suction during microkeratome-assisted
      laser in situ keratomileusis (LASIK) procedure on peripapillary retinal nerve
      fiber layer (RNFL) thickness as well as macular ganglion cell-inner plexiform
      layer (GC-IPL) thickness. METHODS: 89 patients (124 eyes) with established myopia
      range from -3.0 to -8.0 diopters and no associated ocular diseases were included
      in this study. RNFL and GC-IPL thickness measurements were performed by spectral
      domain optical coherence tomography (SD OCT) one day before LASIK and at 1 and 6
      months postoperatively. RESULTS: Mean RNFL thickness prior to LASIK was 93.86 +/-
      12.17 MUm while the first month and the sixth month postoperatively were 94.01 +/
      12.04 MUm and 94.46 +/- 12.27 MUm, respectively. Comparing results, there is no
      significant difference between baseline, one month, and six months
      postoperatively for mean RNFL (p > 0.05). Mean GC-IPL thickness was 81.70 +/-
      7.47 MUm preoperatively with no significant difference during the follow-up
      period (82.03 +/- 7.69 MUm versus 81.84 +/- 7.64 MUm; p > 0.05). CONCLUSION: RNFL
      and GC-IPL complex thickness remained unaffected following LASIK intervention.

PMID- 29018821
TI  - Factors Affecting Unscheduled Return Visits to the Emergency Department among
      Minor Head Injury Patients.
AB  - STUDY OBJECTIVES: Differences between returning and non-returning minor head
      injury (MHI) emergency department (ED) patients, between the characteristics of
      the first visit and revisit, and between admitted and nonadmitted returning
      patients were investigated. METHODS: This was a retrospective study. All
      discharged ED patients with ICD-9 codes 850.0 to 850.9, 920, and 959.01 in 2013
      were enrolled. Patients' demographic data, vital signs, Glasgow Coma Scale, ED
      diagnosis, length of stay, triage levels, ED examinations performed, and
      comorbidities were recorded for analysis. RESULTS: A total of 2,815 patients were
      enrolled. Of 57 (2%) patients who revisited the ED, 47 (82%) were discharged from
      the ED and ten (18%) were admitted to the hospital. Patients who returned to the
      ED were older, and they exhibited more comorbidities. Those who presented with
      vomiting, triage level of 1 or 2, and GCS score of <15 and who received more
      blood tests during their first visit were more likely to be admitted when they
      returned to the ED. CONCLUSIONS: Discharging MHI patients who are older or
      exhibit comorbidities only when symptoms and concerns are relieved completely,
      providing clear discharge instructions, and arranging timely clinical follow-ups
      may help reduce such patients' return rate.

PMID- 29018822
TI  - Expression of Neurotrophin-3 and trkC following Focal Cerebral Ischemia in Adult
      Rat Brain with Treadmill Exercise.
AB  - Neurotrophin-3 (NT-3) is a neurotrophic factor that mainly binds to the tyrosine
      kinase C (trkC) receptor. NT-3 has been shown to have neuroprotective effects in
      focal cerebral ischemia. Exercise also has ability to induce functional recovery
      in focal cerebral ischemia. However, the relationship between NT-3, its receptor
      trkC, and exercise has not been revealed. In this study, we assessed the
      expressions of NT-3 and trkC in focal cerebral ischemia. We also assessed the
      expression of NT-3 and trkC with treadmill exercise in focal cerebral ischemia.
      The results showed that, in a permanent middle cerebral artery occlusion rat
      model, exercise increased NT-3 and trkC expression. However, the patterns of
      expression of NT-3 and trkC at different time points varied. These results
      suggest that exercise-induced functional recovery in focal cerebral ischemia was
      related to NT-3 and trkC, but the role on times of NT-3 and trkC differed,
      although trkC is the receptor kinase for NT-3.

PMID- 29018823
TI  - A High Frequency Geometric Focusing Transducer Based on 1-3 Piezocomposite for
      Intravascular Ultrasound Imaging.
AB  - Due to the small aperture of blood vessel, a considerable disadvantage to current
      intravascular ultrasound (IVUS) imaging transducers is that their lateral imaging
      resolution is much lower than their axial resolution. To solve this problem, a
      single-element, 50 MHz, 0.6 mm diameter IVUS transducer with a geometric focus at
      3 mm was proposed in this paper. The focusing transducer was based on a geometric
      shaped 1-3 piezocomposite. The impedance/phase, pulse echo, acoustic intensity
      field, and imaging resolution of the focusing transducer were tested. For
      comparison, a flat IVUS transducer with the same diameter and 1-3 piezocomposite
      was made and tested too. Compared with their results, the fabricated focusing
      transducer exhibits broad bandwidth (107.21%), high sensitivity (404 mV), high
      axial imaging resolution (80 MUm), and lateral imaging resolution (100 MUm). The
      experimental results demonstrated that the high frequency geometric focusing
      piezocomposite transducer is capable of visualizing high axial and lateral
      resolution structure and improving the imaging quality of related interventional
      ultrasound imaging.

PMID- 29018824
TI  - Leadership and Bullying in the Forestry Organization of Turkey.
AB  - It is observed that the importance of executive-employee relationships is
      continuously increasing in today's professional life in addition to the
      importance of leadership types of managers along with the efficiency of employees
      as well as the sufficiency of these people in their social relations.
      Communication of employees with one another and with their manager, along with
      their social relations, is among the most important factors that sustain an
      organization. Bullying is a kind of psychological terror that takes place in the
      form of repeated attacks among workers, as well as by the manager on the
      employees, aiming to instill stress, job dissatisfaction, and exhaustion on the
      employees. It has been put forth especially by recent studies that the leadership
      styles of the managers are highly influential on bullying. The study was carried
      out with 1189 forest engineers working at 25 different Regional Directorates of
      Forestry in Turkey. The status of engineers subject to bullying in addition to
      the effects of leadership types on bullying was determined as a result of the
      statistical analyses carried out. The results of the study were evaluated
      comprehensively in comparison with other studies in the relevant literature, thus
      developing suggestions for preventing bullying behaviors that vary across
      leadership types.

PMID- 29018825
TI  - Relationship between Metabolic Syndrome and Ocular Microcirculation Shown by
      Laser Speckle Flowgraphy in a Hospital Setting Devoted to Sleep Apnea Syndrome
      Diagnostics.
AB  - PURPOSE: To clarify whether the incidence of metabolic syndrome (MetS) and the
      overlap of MetS components are affecting the ocular circulation shown by laser
      speckle flowgraphy (LSFG). MATERIALS AND METHODS: We studied 76 consistent
      patients. Blowout score (BOS) and blowout time (BOT), which are the pulse
      waveform analysis parameters, and mean blur rate (MBR) using LSFG in the optic
      nerve head (ONH) and choroid were evaluated. Throughout, the ONH was separated
      out from the vessels and tissue for analysis and MBRs in the ONH were divided
      into four sections (superior, temporal, inferior, and nasal). RESULTS: Thirty-two
      patients were diagnosed having Mets. MBR-Tissue (P = 0.003), MBR-All (P = 0.01),
      MBR-Choroid (P = 0.04), and BOS-Choroid (P = 0.03) were significantly lower in
      patients with MetS than in the patients without MetS. Multiple-regression
      analysis revealed the temporal side of MBR-Tissue and BOS-Choroid which were
      identified as factors contributing independently to the overlap of the MetS
      components. Multiple-regression analysis also revealed that the MetS components
      were identified to be factors independently contributing to the BOS-Choroid and
      temporal side of MBR-Tissue. CONCLUSION: Our study clarified that the incidence
      of MetS and the overlap of the MetS components are significantly affecting the
      ONH and choroidal microcirculation.

PMID- 29018826
TI  - High Prevalence of Autoimmune Diabetes and Poor Glycaemic Control among Adults in
      Madagascar: A Brief Report from a Humanitarian Health Campaign in Ambanja.
AB  - Madagascar is a geographically isolated country considered a biodiversity hotspot
      with unique genomics. Both the low-income and the geographical isolation
      represent risk factors for the development of diabetes. During a humanitarian
      health campaign conducted in Ambanja, a rural city in the northern part of
      Madagascar, we identified 42 adult subjects with diabetes and compared their
      features to 24 randomly enrolled healthy controls. 42.9% (n = 18) of diabetic
      subjects showed HbA1c values >= 9.0%. Unexpectedly, waist circumference and BMI
      were similar in people with diabetes and controls. Different from the healthy
      controls, diabetic subjects showed a low prevalence of obesity (5.7% versus 30%,
      p = 0.02). Accordingly, we found a high prevalence of autoimmune diabetes as 12%
      of people with diabetes showed positivity for the autoantibody against glutamic
      acid decarboxylase. Diabetic subjects with positive autoantibody had higher HbA1c
      values (11.3 +/- 4.1% versus 8.3 +/- 2.6%, p = 0.03) compared to diabetic
      subjects with negative autoantibody. In conclusion, here we describe the presence
      of diabetes and its features in a rural area of Northern Madagascar, documenting
      poor glycaemic control and a high prevalence of autoimmune diabetes. These data
      highlight that the diabetes epidemic involves every corner of the world possibly
      with different patterns and features.

PMID- 29018827
TI  - Low Levels of Usual Physical Activity Are Associated with Higher 24 h Blood
      Pressure in Type 2 Diabetes Mellitus in a Cross-Sectional Study.
AB  - The aim of this study is to evaluate the association between usual physical
      activity and 24 h blood pressure (BP) profile in people with type 2 diabetes
      mellitus (DM). This is a cross-sectional study of 151 participants with type 2
      DM. Usual physical activity was assessed by step counting and self-reported
      questionnaire. BP was measured in office and by 24 h ambulatory BP monitoring
      (ABPM; 24 h, daytime and nighttime). Mean participant age was 61.1 +/- 8.4 years,
      64% was women, and mean duration of diabetes was 14.3 +/- 8.5 years. Ninety-two
      percent of participants had hypertension, and office BP was 138 +/- 18/78 +/- 10
      mmHg. Inverse correlations were observed between step count and 24 h BP
      (systolic, r = -0.186; p = 0.022), daytime BP (systolic, r = -0.198; p = 0.015),
      and nighttime BP (pulse pressure, r = -0.190; p = 0.019). People were categorized
      into tertiles of daily step count, and the 1st tertile had higher 24 h systolic
      BP, daytime systolic BP, daytime mean BP, and daytime systolic BP load than those
      in the other tertiles, even after adjusting for age and HbA1c. Participants with
      type 2 DM and low levels of physical activity exhibit higher 24 h and daytime
      systolic ambulatory BP values as compared with those who performed more steps per
      day, even after adjustments for confounding factors.

PMID- 29018829
TI  - Comparative Efficacy of Topical Pertmehrin, Crotamiton and Sulfur Ointment in
      Treatment of Scabies.
AB  - BACKGROUND: Scabies is an ectoparasitic infection, which occurs because of direct
      skin-to skin contact. The ideal treatment modality is still unclear and further
      research on this topic is warranted. The aim of the study was to compare the
      efficacy and safety of the topical scabicides: permethrin, crotamiton and sulfur
      ointment. METHODS: Fifty four patients with diagnosed scabies were randomly
      divided into three treatment groups. The first group received 5% permethrin cream
      twice with one week interval, the patients from the second group were given
      crotamiton lotion for two days twice with one week interval, while the third
      group received 10% sulfur ointment for two or three weeks. All patients were
      followed up at 1, 2 and 4 weeks intervals. RESULTS: At one-week follow up the
      cure rate was significantly higher at permethrin-treated group when compared to
      crotamiton group (P< 0.001) and sulfur group (P< 0.001). At the end of two-week
      interval, the cure rate at permethrin group was 100%, while at crotamiton group,
      66.7% and in sulfur group 38.9% (P< 0.001). At 4-week follow up the applied
      treatment was effective in all studied individuals. CONCLUSION: The topical
      application of permethrin, crotamiton and sulfur was equally efficacious at 4
      week follow up, however permethrin cream showed faster improvement at first and
      second follow up. Acquiring permethrin is considered as expensive option and
      crotamiton lotion seems to be cost-less alternative to this cream.

PMID- 29018830
TI  - Antivenom Efficacy in Neutralizing Histopathological Complications Following
      Latrodectus dahli Envenomation.
AB  - BACKGROUND: Nowadays use of specific antivenin for latrodectism is considered as
      the most effective treatment in the world. This study was undertaken to
      investigate the efficacy of specific antivenom against histopathological
      complications caused by Latrodectus dahli venom on liver, heart and kidneys
      tissues within 72h. METHODS: Two groups were selected, each one contained 6 male
      New Zealand rabbits weighing 2+/-0.5kg. The animals were anesthetized with 0.5ml
      ketamine and 0.5ml xylazine by intramuscular route. The L. dahli venom (0.5mg/kg)
      was injected subcutaneously to both the groups. The second group of rabbits 24h
      after the venom injection received specific antivenom by intravenous route.
      Seventy-two hours after the venom and antivenom injections, the rabbits were
      dissected to obtain heart, liver and kidney tissues. The tissues were stained by
      hematoxylin and eosin stains and histopathological studies were examined by
      optical microscope. RESULTS: In group one, the venom induced myocytolysis,
      myocarditis, coagulation necrosis in the heart tissue and the liver tissue showed
      central vein congestion, congested vessels, dilated sinusoids and inflammation.
      However, no significant histopathological complications were observed in kidney
      tissues. In the second group, antivenom injection greatly prevented escalation of
      the complications on foresaid tissues. CONCLUSION: Latrodectus dahli venom
      induces histopathological complications on vital organs. Specific antivenom
      injection, 24h after the venom injection, could protect the tissues from
      incidence and intensification of histopathological complications. Future studies
      in human beings should be conducted to assess the protection against the specific
      Latrodectus antivenin.

PMID- 29018828
TI  - Repurposing Lesogaberan to Promote Human Islet Cell Survival and beta-Cell
      Replication.
AB  - The activation of beta-cell's A- and B-type gamma-aminobutyric acid receptors
      (GABAA-Rs and GABAB-Rs) can promote their survival and replication, and the
      activation of alpha-cell GABAA-Rs promotes their conversion into beta-cells.
      However, GABA and the most clinically applicable GABA-R ligands may be suboptimal
      for the long-term treatment of diabetes due to their pharmacological properties
      or potential side-effects on the central nervous system (CNS). Lesogaberan
      (AZD3355) is a peripherally restricted high-affinity GABAB-R-specific agonist,
      originally developed for the treatment of gastroesophageal reflux disease (GERD)
      that appears to be safe for human use. This study tested the hypothesis that
      lesogaberan could be repurposed to promote human islet cell survival and beta
      cell replication. Treatment with lesogaberan significantly enhanced replication
      of human islet cells in vitro, which was abrogated by a GABAB-R antagonist.
      Immunohistochemical analysis of human islets that were grafted into immune
      deficient mice revealed that oral treatment with lesogaberan promoted human beta
      cell replication and islet cell survival in vivo as effectively as GABA (which
      activates both GABAA-Rs and GABAB-Rs), perhaps because of its more favorable
      pharmacokinetics. Lesogaberan may be a promising drug candidate for clinical
      studies of diabetes intervention and islet transplantation.

PMID- 29018831
TI  - Mediterranean Recluse Spider, Loxosceles rufescens (Araneae: Sicariidae) from
      Charkhab Cave, Southern Iran.
AB  - BACKGROUND: The best-known dangerous spiders belong to the six genera. The genus
      Loxosceles or violin spiders are well known for their ability to cause skin
      necrosis or loxoscelism. All Loxosceles species have medical importance due to
      their necrotizing venom. The present article reports the occurrence of L.
      rufescens in Charkhab Cave, south of Iran (Larestan). METHODS: The specimens were
      collected from the Charkhab Cave using handling forceps, paintbrush and aspirator
      and preserved in 96% ethanol. RESULTS: Loxosceles rufescens, a medically
      important spider, is recorded from Charkhab Cave in Fars Province (southwest of
      Iran). Identification of L. rufescens was performed based on external morphology
      and the features of male genitalia. CONCLUSION: Presence of L. rufescens in south
      of Iran especially in a cave confirmed that this species is a widely distributed
      species in Iran. Therefore, cavers or cave visitors should be aware of this
      poisonous spider in caves.

PMID- 29018832
TI  - Pharyngeal Myiasis Caused by Sheep Botfly, Oestrus ovis (Diptera: Oestridae)
      Larva, Tabriz, East Azarbaijan Province, Iran: a Case Report.
AB  - Myiasis is caused by the larvae of flies infesting animal or human tissues and
      organs. This report aims to present a case of pharyngeal myiasis caused by the
      larvae of Oestrus ovis (Diptera: Oestridae). A 55-yr old drug addict living in
      the Shahindeje village of Western Azerbaijan Province, northwestern Iran was
      referred to the Emam Reza Hospital in Tabriz, having a medical history of Chronic
      Obstructive Pulmonary Disease (COPD) and hospitalized due to respiratory
      distress, 20 days ago. He was intubated with a mechanical ventilator (MV) because
      of his respiratory distress condition. There was an evidence of the presence of
      pulmonary nodules in his lungs following diagnosis, and a CT scan revealed a
      cavity in his lung. During the nasogastric intubation procedure, a larva was seen
      emerging from the patient's mouth by one of the staff of the intensive care unit
      of the hospital. A laboratory diagnosis was performed in the Entomology
      Department of the School of Medicine, Tabriz University of Medical Sciences.
      Interestingly, larvae of O. ovis were identified and confirmed following the
      laboratory proceedings.

PMID- 29018833
TI  - Sand Fly Fever with Different Names.

PMID- 29018835
TI  - 13C/31P MRS Metabolic Biomarkers of Disease Progression and Response to AAV
      Delivery of hGAA in a Mouse Model of Pompe Disease.
AB  - The development of therapeutic clinical trials for glycogen storage disorders,
      including Pompe disease, has called for non-invasive and objective biomarkers.
      Glycogen accumulation can be measured in vivo with 13C MRS. However, clinical
      implementation remains challenging due to low signal-to-noise. On the other hand,
      the buildup of glycolytic intermediates may be detected with 31P MRS. We sought
      to identify new biomarkers of disease progression in muscle using 13C/31P MRS and
      1H HR-MAS in a mouse model of Pompe disease (Gaa-/-). We evaluated the
      sensitivity of these MR biomarkers in vivo after treatment using an adeno
      associated virus vector 2/9 encoding hGAA driven by the desmin promotor. 31P MRS
      showed significantly elevated phosphomonoesters (PMEs) in Gaa-/- compared to
      control at 2 (0.06 +/- 0.02 versus 0.03 +/- 0.01; p = 0.003), 6, 12, and 18
      months of age. Correlative 1H HR-MAS measures in intact gastrocnemius muscles
      revealed high glucose-6-phosphate (G-6-P). After intramuscular AAV injections,
      glycogen, PME, and G-6-P were decreased within normal range. The changes in PME
      levels likely partly resulted from changes in G-6-P, one of the overlapping
      phosphomonoesters in the 31P MR spectra in vivo. Because 31P MRS is inherently
      more sensitive than 13C MRS, PME levels have greater potential as a clinical
      biomarker and should be considered as a complementary approach for future studies
      in Pompe patients.

PMID- 29018834
TI  - In Situ Liver Expression of HBsAg/CD3-Bispecific Antibodies for HBV
      Immunotherapy.
AB  - Current therapies against hepatitis B virus (HBV) do not reliably cure chronic
      infection, necessitating new therapeutic approaches. The T cell response can
      clear HBV during acute infection, and the adoptive transfer of antiviral T cells
      during bone marrow transplantation can cure patients of chronic HBV infection. To
      redirect T cells to HBV-infected hepatocytes, we delivered plasmids encoding
      bispecific antibodies directed against the viral surface antigen (HBsAg) and CD3,
      expressed on almost all T cells, directly into the liver using hydrodynamic tail
      vein injection. We found a significant reduction in HBV-driven reporter gene
      expression (184-fold) in a mouse model of acute infection, which was 30-fold
      lower than an antibody only recognizing HBsAg. While bispecific antibodies
      triggered, in part, antigen-independent T cell activation, antibody production
      within hepatocytes was non-cytotoxic. We next tested the bispecific antibodies in
      a different HBV mouse model, which closely mimics the transcriptional template
      for HBV, covalently closed circular DNA (cccDNA). We found that the antiviral
      effect was noncytopathic, mediating a 495-fold reduction in HBsAg levels at day
      4. At day 33, bispecific antibody-treated mice exhibited 35-fold higher host
      HBsAg immunoglobulin G (IgG) antibody production versus untreated groups. Thus,
      gene therapy with HBsAg/CD3-bispecific antibodies represents a promising
      therapeutic strategy for patients with HBV.

PMID- 29018836
TI  - One-Step Fabrication of Bone Morphogenetic Protein-2 Gene-Activated Porous Poly-L
      Lactide Scaffold for Bone Induction.
AB  - Bone morphogenetic protein 2 (BMP2) is an efficacious inducer for the
      osteogenesis of mesenchymal stem cells (MSCs). Conventional applications of BMP2
      have involved either the direct incorporation of BMP2 protein or ex vivo BMP2
      gene transfer into stem cells prior to their transplantation. These approaches
      are able to promote bone formation to some extent; however, they are hampered by
      either the lack of stability and sustainability of BMP2 protein or the time
      consuming and cost-prohibitive in vitro cell culture procedure. To overcome these
      limitations, we have developed a gene-activated poly-L-lactide acid (PLLA)
      scaffold with the encapsulation of recombinant adeno-associated viral (AAV)
      vector encoding a full-length cDNA of human BMP2 using an ice-based microparticle
      porogenization method that was recently developed. Results showed continuous
      release of AAV particles from the micropores of scaffolds for up to 1 week,
      subsequently transducing embedded human MSCs and producing functional BMP2. MSCs
      within scaffolds underwent efficacious osteogenesis, on the basis of
      osteoinductive gene expression and osteogenic differentiation, which resulted in
      robust new bone formation in vivo at 4 weeks. These findings show the potential
      of the technology toward developing clinical applications of a rapid, cost
      effective, and potentially point-of-care approach for the repair of bone defects.

PMID- 29018837
TI  - Bone mineral density and breast cancer risk: Results from the Vorarlberg Health
      Monitoring & Prevention Program and meta-analysis.
AB  - We investigated the association between bone mineral density (BMD) and breast
      cancer risk in a large prospective cohort and quantified the evidence in a meta
      analysis of prospective studies. Baseline BMD has been measured by dual energy X
      ray absorptiometry (DXA, N = 1418). Data on medication and lifestyle has been
      collected by questionnaire. Cox proportional Hazards models were applied to
      calculate Hazard Ratios for breast cancer. In addition, a meta-analysis on
      categorical and dose-response values including the current results has been
      performed applying random-effects models. During mean follow-up of 16.3 (SD 3.3)
      years of 1380 women (mean age 55.5 +/- 6.3 years), 52 cases of invasive breast
      cancer were identified. We found no statistically significant association of BMD
      with breast cancer risk (per one z-score increase, HR 0.91, 95% CI 0.67-1.23). In
      the meta-analysis, however, breast cancer risk increased by 15% and 16% per 0.1
      g/m2 increase in BMD at the lumbar spine (95% CI 0.99-1.33) and at the femoral
      neck (95% CI 1.02-1.32), respectively. Compared to the lowest, the HRs for breast
      cancer were statistically significant for the highest BMD category, i.e. 1.49
      (95% CI 1.04-2.13) at the lumbar spine and 1.66 (95% CI 1.26-2.18) at the femur.
      We found no association between BMD (DXA) and breast cancer risk in our cohort.
      However, overall the present meta-analysis extends and confirms the statistically
      significant association between increasing BMD and increased breast cancer risk.

PMID- 29018838
TI  - Adverse post-operative outcomes in Jehovah's witnesses with gynecologic cancer
      within 30 days of surgery: A single institution review of 36 cases.
AB  - Rates of blood transfusion are reported as high as 32% in women undergoing major
      gynecologic cancer surgery. Therefore, care of the gynecologic oncology patient
      who refuses blood products, such as Jehovah's witnesses, can pose a unique
      challenge. The objective of this study was to determine rate of adverse post
      operative outcomes within 30 days of surgery in Jehovah's witnesses with
      gynecologic cancer. This was a retrospective cohort study of Jehovah's witnesses
      undergoing laparotomy or minimally invasive surgery (MIS) for gynecologic cancer
      at a single institution. Data for post-adverse complications within 30 days of
      surgery were recorded. In total, 36 patients were included with a median age of
      58.5 years (32-85 years). The majority had endometrial adenocarcinoma (n = 23;
      63.9%) or epithelial ovarian, fallopian tube or peritoneal cancer (EOC) (n = 8;
      22.2%). 61.1% (n = 22) of patients underwent laparotomy and 38.9% (n = 14) had
      MIS procedures. 31.8% of laparotomies (n = 7) were terminated prematurely due to
      surgeon concern for ongoing blood loss. In patients with advanced stage EOC, the
      rate of suboptimal cytoreduction (> 1 cm) was 50%. In the laparotomy cohort,
      there were four (18.2%) ICU admissions and two (9.1%) mortalities. The time to
      adjuvant chemotherapy or radiation was 45.5 days (31-64) for laparotomy compared
      to 35.0 days (12-64) for MIS. While the majority of patients (97.2%) were
      unwilling to accept packed red blood cells, over one third (38.9%) were agreeable
      to autologous blood transfusion. Additionally, five (13.9%) patients were
      accepting of fresh frozen plasma, six (16.7%) patients were agreeable to
      cryoprecipitate and seven (19.4%) patients were willing to accept platelet
      transfusions. There is a high rate of postoperative adverse outcomes among
      Jehovah's witnesses undergoing laparotomy for gynecologic malignancy compared.
      Acceptance of blood products is low among Jehovah's witnesses, even in the
      setting of major oncologic surgery.

PMID- 29018839
TI  - Clinical Assessment of Physical Examination Maneuvers for Superior Labral
      Anterior to Posterior Lesions.
AB  - Purpose  Shoulder pain and disability pose a diagnostic challenge owing to the
      numerous etiologies and the potential for multiple disorders to exist
      simultaneously. The evidence to support the use of clinical tests for superior
      labral anterior to posterior complex (SLAP) is weak or absent. The purpose of
      this study is to determine the diagnostic validity of physical examination
      maneuvers for SLAP lesions by performing a methodologically rigorous, clinically
      applicable study. Methods  We recruited consecutive new shoulder patients
      reporting pain and/or disability. The physician took a history and indicated
      their certainty about each possible diagnosis ("certain the diagnosis is
      absent/present," or "uncertain requires further testing"). The clinician
      performed the physical tests for diagnoses where uncertainty remained. Magnetic
      resonance imaging arthrogram and arthroscopic examination were the gold
      standards. We calculated sensitivity, specificity, and likelihood ratios (LRs)
      and investigated whether combinations of the top tests provided stronger
      predictions. Results  Ninety-three patients underwent physical examination for
      SLAP lesions. When using the presence of a SLAP lesion (Types I-V) as disease
      positive, none of the tests was sensitive (10.3-33.3) although they were
      moderately specific (61.3-92.6). When disease positive was defined as repaired
      SLAP lesion (including biceps tenodesis or tenotomy), the sensitivity (10.5-38.7)
      and specificity (70.6-93.8) of tests improved although not by a substantial
      amount. None of the tests was found to be clinically useful for predicting
      repairable SLAP lesions with all LRs close to one. The compression rotation test
      had the best LR for both definitions of disease (SLAP tear present = 1.8 and SLAP
      repaired = 1.67). There was no optimal combination of tests for diagnosing
      repairable SLAP lesions, with at least two tests positive providing the best
      combination of measurement properties (sensitivity 46.1% and specificity 64.7%).
      Conclusion  Our study demonstrates that the physical examination tests for SLAP
      lesions are poor diagnostic indicators of disease. Performing a combination of
      tests will likely help, although the magnitude of the improvement is minimal.
      These authors caution clinicians placing confidence in the physical examination
      tests for SLAP lesions rather we suggest that clinicians rely on diagnostic
      imaging to confirm this diagnosis.

PMID- 29018840
TI  - Sharing individual patient and parasite-level data through the WorldWide
      Antimalarial Resistance Network platform: A qualitative case study.
AB  - BACKGROUND: Increasingly, biomedical researchers are encouraged or required by
      research funders and journals to share their data, but there's very little
      guidance on how to do that equitably and usefully, especially in resource
      constrained settings. We performed an in-depth case study of one data sharing
      pioneer: the WorldWide Antimalarial Resistance Network (WWARN). METHODS: The case
      study included a records review, a quantitative analysis of WAARN-related
      publications, in-depth interviews with 47 people familiar with WWARN, and a
      witness seminar involving a sub-set of 11 interviewees. RESULTS: WWARN originally
      aimed to collate clinical, in vitro, pharmacological and molecular data into
      linked, open-access databases intended to serve as a public resource to guide
      antimalarial drug treatment policies. Our study describes how WWARN navigated
      challenging institutional and academic incentive structures, alongside funders'
      reluctance to invest in capacity building in malaria-endemic countries, which
      impeded data sharing. The network increased data contributions by focusing on
      providing free, online tools to improve the quality and efficiency of data
      collection, and by inviting collaborative authorship on papers addressing policy
      relevant questions that could only be answered through pooled analyses. By July
      1, 2016, the database included standardised data from 103 molecular studies and
      186 clinical trials, representing 135,000 individual patients. Developing the
      database took longer and cost more than anticipated, and efforts to increase
      equity for data contributors are on-going. However, analyses of the pooled data
      have generated new methods and influenced malaria treatment recommendations
      globally. Despite not achieving the initial goal of real-time surveillance, WWARN
      has developed strong data governance and curation tools, which are now being
      adapted relatively quickly for other diseases. CONCLUSIONS: To be useful, data
      sharing requires investment in long-term infrastructure. To be feasible, it
      requires new incentive structures that favour the generation of reusable
      knowledge.

PMID- 29018841
TI  - A framework for Controlled Human Infection Model (CHIM) studies in Malawi: Report
      of a Wellcome Trust workshop on CHIM in Low Income Countries held in Blantyre,
      Malawi.
AB  - Controlled human infection model (CHIM) studies have pivotal importance in
      vaccine development, being useful for proof of concept, pathogenesis, down
      selection and immunogenicity studies.  To date, however, they have seldom been
      carried out in low and middle income countries (LMIC), which is where the
      greatest burden of vaccine preventable illness is found.  This workshop discussed
      the benefits and barriers to CHIM studies in Malawi.  Benefits include improved
      vaccine effectiveness and host country capacity development in clinical,
      laboratory and governance domains.  Barriers include acceptability, safety and
      regulatory issues. The report suggests a framework by which ethical, laboratory,
      scientific and governance issues may be addressed by investigators considering or
      planning CHIM in LMIC.

PMID- 29018843
TI  - Acceleration and suppression of banana-shaped-protein-induced tubulation by
      addition of small membrane inclusions of isotropic spontaneous curvatures.
AB  - Membrane tubulation induced by banana-shaped protein rods is investigated by
      using coarse-grained meshless membrane simulations. It is found that tubulation
      is promoted by laterally isotropic membrane inclusions that generate the same
      sign of spontaneous curvature as the adsorbed protein rods. The inclusions are
      concentrated in the tubules and reduce the bending energy of the tip of the
      tubules. On the other hand, inclusions with an opposite curvature suppress
      tubulation by percolated-network formation at a high protein-rod density while
      they induce the formation of a spherical membrane bud at a low rod density. When
      equal amounts of the two types of inclusions (with positive and negative
      curvatures) are added, their effects cancel each other for the first short period
      but later the tubulation is slowly accelerated. Positive surface tension
      suppresses tubulation. Our results suggest that the cooperation of scaffolding of
      BAR (Bin/Amphiphysin/Rvs) domains and isotropic membrane inclusions is important
      for tubulation.

PMID- 29018842
TI  - First detection of N1575Y mutation in pyrethroid resistant Anopheles gambiae in
      Southern Cote d'Ivoire.
AB  - Background. The intensification of insecticide use for both public health and
      agriculture in Africa has contributed to growing insecticide resistance. Today,
      resistance to World Health Organization (WHO)-approved insecticide classes is
      widespread. In an agricultural area of Southern Cote d'Ivoire, the main malaria
      vector Anopheles coluzzii shows multiple resistance across insecticides mediated
      by both target site mutation and metabolic mechanisms. To plan new vector control
      strategies and avert future resistance liabilities caused by cross-resistance
      mechanisms extant within populations, it is crucial to monitor the development
      and spread of both resistance and mechanisms. Methods.  Larvae of Anopheles
      gambiae were collected from natural breeding sites in Tiassale and Elibou,
      between April and November 2016 and raised to adults . Adult female non-blood fed
      mosquitoes, three to five days old, were exposed to deltamethrin in WHO
      bioassays. Extracted DNA samples from exposed mosquitoes were used for species
      characterisation and genotyping. Results. Most adult An. gambiae tested were
      resistant to deltamethrin, with mortality rates of only 25% in Tiassale and 4.4%
      in Elibou. Molecular analysis of DNA from samples tested showed the presence of
      both An. coluzzii and An. gambiae s.s in Elibou and only An. coluzzii for
      Tiassale. As previously, the L1014F kdr mutation was present at high frequency
      (79%) in Tiassale and the L1014S mutation was absent. The N1575Y mutation, which
      amplifies resistance conferred by L1014F was detected in a single unique
      individual from a Tiassale An. coluzzii female whereas in Elibou 1575Y was
      present in 10 An. gambiae s.s, but not in An. coluzzii. Conclusion. This is the
      first report of the N1575Y mutation in Cote d'Ivoire, and as in other
      populations, it is found in both dominant West African malaria vector species.
      Continued monitoring of N1575Y is underway, as are studies to elucidate its
      contribution to the resistance of local vector populations.

PMID- 29018844
TI  - Thermally-induced lateral assembly of a PEG-containing amphiphile triggering
      vesicle budding.
AB  - A macrocyclic amphiphile consisting of a thermo-responsive octaethylene glycol
      chain with hydrophobic aromatic and aliphatic units undergoes lateral self
      assembly in a liquid-disordered-state phospholipid bilayer membrane upon heating,
      which further leads to vesicle budding.

PMID- 29018845
TI  - Controlled self-sorting in self-assembled cage complexes.
AB  - In this frontier article we highlight recent advances in subcomponent self
      sorting in self-assembled metal-ligand cage complexes, with a focus on selective
      discrimination between ligands that contain highly similar metal-coordinating
      groups. Effects such as varying ligand length, coordination angle and backbone
      flexibility, as well as the introduction of secondary weak forces such as
      hydrogen bonds can be exploited to favor either narcissistic or social self
      sorting. We highlight these creative solutions, and emphasize the challenges that
      remain in the development of functional self-assembled heterocomplexes.

PMID- 29018846
TI  - Antibiotics and specialized metabolites from the human microbiota.
AB  - Covering: 2000 to 2017Decades of research on human microbiota have revealed much
      of their taxonomic diversity and established their direct link to health and
      disease. However, the breadth of bioactive natural products secreted by our
      microbial partners remains unknown. Of particular interest are antibiotics
      produced by our microbiota to ward off invasive pathogens. Members of the human
      microbiota exclusively produce evolved small molecules with selective
      antimicrobial activity against human pathogens. Herein, we expand upon the
      current knowledge concerning antibiotics derived from human microbiota and their
      distribution across body sites. We analyze, using our in-house chem-bioinformatic
      tools and natural products database, the encoded antibiotic potential of the
      human microbiome. This compilation of information may create a foundation for the
      continued exploration of this intriguing resource of chemical diversity and
      expose challenges and future perspectives to accelerate the discovery rate of
      small molecules from the human microbiota.

PMID- 29018848
TI  - A gold(i)-catalyzed intramolecular tandem cyclization reaction of
      alkylidenecyclopropane-containing alkynes.
AB  - A novel gold(i)-catalyzed intramolecular tandem cyclization reaction of ortho
      (arylethynyl)arenemethylenecyclopropanes provided an efficient approach to
      prepare functionalized 11H-benzo[a]fluorene derivatives in moderate to good
      yields. Further transformations as well as applications of the products have been
      presented and a plausible reaction mechanism has also been proposed on the basis
      of deuterium labeling and control experiments.

PMID- 29018847
TI  - The reactivity of phenylethanethiolated gold nanoparticles with acetic acid.
AB  - We report the size-dependent reactivity of phenylethanethiolated gold
      nanoparticles with acetic acid. Employing this reactivity, we synthesize a novel
      nanocluster Au38(PET)26 (PET: phenylethanethiolate), which is otherwise difficult
      to obtain and exhibits remarkably different photoluminescence and electrochemical
      properties compared with the well-known Au38(PET)24 nanoclusters. And the
      reaction process between Au38(PET)26 and acetic acid was probed by matrix
      assisted laser desorption/ionization time of flight mass spectrometry.

PMID- 29018849
TI  - Construction of (3,6)-connected polyoxometalate-based metal-organic frameworks
      (POMOFs) from triangular carboxylate and dimerized Zn4-epsilon-Keggin.
AB  - Using the methodology of extension of reduced transition metal-grafted epsilon
      Keggin polyoxoanions with two types of terphenyl-based tricarboxylates of H3L1
      (3,5',3''-position substitution) and H3L2 (4,5',4''-position substitution) we
      isolated two (3,6)-connected 3D polyoxometalate-based metal-organic frameworks,
      [TBA]3[H3PMo12O40][Zn4L2] (1, YZU-105), and [TPA]3[H3PMo12O40][Zn4L1].0.5H2O (2,
      YZU-106) (H3L1 = [1,1';3',1''-terphenyl]-3,5',3''-tricarboxylic acid; H3L2 =
      [1,1';3',1''-terphenyl]-4,5',4''-tricarboxylic acid; TBA = tetrabutylammonium;
      TPA = tetrapropylammonium). In both compounds, the building block was the
      dimerized form of Zn4-{epsilon-H3PMo12O40}. Such dimerization left six anchoring
      points for each dimer and, as a result, a 6-connected node was formed. Compounds
      1 and 2 exhibited topologies of (4.85)3(4.82)6 and (65.10)3(63)6, respectively.
      This work illustrates that use of tri-carboxylate substitutions in different
      positions (3,5',3''-position/4,5',4''-position) in tripodal terphenyl-based
      ligands allows different extents of twisting of the peripheral aromatic ring with
      respect to the central ring, thereby giving rise to different extending
      directions and symmetries.

PMID- 29018850
TI  - Optimising minimal building blocks for addressable self-assembly.
AB  - Addressable structures are characterised by the set of unique components from
      which they are built and by the specific location that each component occupies.
      For an addressable structure to self-assemble, its constituent building blocks
      must be encoded with sufficient information to define their positions with
      respect to each other and to enable them to navigate to those positions. DNA,
      with its vast scope for encoding specific interactions, has been successfully
      used to synthesise addressable systems of several hundred components. In this
      work we examine the complementary question of the minimal requirements for
      building blocks to undergo addressable self-assembly driven by a controlled
      temperature quench. Our testbed is an idealised model of cubic particles
      patterned with attractive interactions. We introduce a scheme for optimising the
      interactions using a variant of basin-hopping and a negative design principle.
      The designed building blocks are tested dynamically in simple target structures
      to establish how their complexity affects the limits of reliable self-assembly.

PMID- 29018851
TI  - Beyond soft chemistry - bulk and surface modifications of polycrystalline
      lepidocrocite titanate induced by post-synthesis thermal treatment.
AB  - While the soft chemistry of layered alkali metal oxides is adequately understood,
      the effect of the post-synthesis thermal treatment on their structure,
      composition, and properties has been underexplored. In this article, we
      thoroughly investigated the bulk and surface modifications of K0.8M0.4Ti1.6O4 (M
      = Ni, Cu, Zn) lepidocrocite titanate thermally treated within 200  degrees C
      above its synthetic temperature under air. This practice was typically employed
      in e.g., specimen fabrication for physical property measurements. We observed the
      expansion of the interlayer distance (b/2) accompanied by a reduction in layer
      charge density. These findings can be explained by the deintercalation of
      interlayer K+ ions and the loss of intralayer Ti, M, and O species. Meanwhile,
      the enrichment of potassium and carbonate on the surfaces was evident. The slight
      differences in dielectric properties of the pellets thermally treated at
      different temperatures were attributed to the combination of bulk and surface
      modifications. At 103 Hz and RT-250  degrees C, the maximum dielectric constants
      epsilon'max of ~104 with the dielectric loss (tan delta) ~0.9-1.5 were obtained
      for K0.8Zn0.4Ti1.6O4.

PMID- 29018852
TI  - Modeling the transformation of atmospheric CO2 into microalgal biomass.
AB  - Marine phytoplankton acts as a considerable sink of atmospheric CO2 as it
      sequesters large quantities of this greenhouse gas for biomass production. To
      assess microalgae's counterbalancing of global warming, the quantities of CO2
      they fix need to be determined. For this task, it is mandatory to understand
      which environmental and physiological parameters govern this transformation from
      atmospheric CO2 to microalgal biomass. However, experimental analyses are
      challenging as it has been found that the chemical environment has a major impact
      on the physiological properties of the microalgae cells (diameter typ. 5-20 MUm).
      Moreover, the cells can only chemically interact with their immediate vicinity
      and thus compound sequestration needs to be studied on a microscopic spatial
      scale. Due to these reasons, computer simulations are a more promising approach
      than the experimental studies. Modeling software has been developed that
      describes the dissolution of atmospheric CO2 into oceans followed by the
      formation of HCO3- which is then transported to individual microalgae cells. The
      second portion of this model describes the competition of different cell species
      for this HCO3-, a nutrient, as well as its uptake and utilization for cell
      production. Two microalgae species, i.e. Dunaliella salina and Nannochloropsis
      oculata, were cultured individually and in a competition situation under
      different atmospheric CO2 conditions. It is shown that this novel model's
      predictions of biomass production are in very good agreement with the
      experimental flow cytometry results. After model validation, it has been applied
      to long-term prediction of phytoplankton generation. These investigations were
      motivated by the question whether or not cell production slows down as cultures
      grow. This is of relevance as a reduced cell production rate means that the
      increase in a culture's CO2-sinking capacity slows down as well. One implication
      resulting from this is that an increase in anthropogenic CO2 may not be
      counterbalanced by an increase in phytoplankton production. Modeling studies have
      found that for several different atmospheric CO2 levels provided to single
      species cultures as well as to species in competing scenarios the cell production
      rate does slow down over time.

PMID- 29018853
TI  - An argyrodite-type Ag9GaSe6 liquid-like material with ultralow thermal
      conductivity and high thermoelectric performance.
AB  - We report a ternary argyrodite-type Ag9GaSe6 compound as a promising
      thermoelectric material in a moderate temperature range. Due to high carrier
      mobility and ultralow lattice thermal conductivity, a maximum ZT of 1.1 was
      obtained with stoichiometric Ag9GaSe6 at 800 K. Via introducing slight Se
      deficiency to optimize the carrier concentration, the maximum ZT is further
      enhanced to 1.3.

PMID- 29018854
TI  - Isotachophoresis applied to biomolecular reactions.
AB  - This review discusses research developments and applications of isotachophoresis
      (ITP) to the initiation, control, and acceleration of chemical reactions,
      emphasizing reactions involving biomolecular reactants such as nucleic acids,
      proteins, and live cells. ITP is a versatile technique which requires no specific
      geometric design or material, and is compatible with a wide range of microfluidic
      and automated platforms. Though ITP has traditionally been used as a purification
      and separation technique, recent years have seen its emergence as a method to
      automate and speed up chemical reactions. ITP has been used to demonstrate up to
      14 000-fold acceleration of nucleic acid assays, and has been used to enhance
      lateral flow and other immunoassays, and even whole bacterial cell detection
      assays. We here classify these studies into two categories: homogeneous (all
      reactants in solution) and heterogeneous (at least one reactant immobilized on a
      solid surface) assay configurations. For each category, we review and describe
      physical modeling and scaling of ITP-aided reaction assays, and elucidate key
      principles in ITP assay design. We summarize experimental advances, and identify
      common threads and approaches which researchers have used to optimize assay
      performance. Lastly, we propose unaddressed challenges and opportunities that
      could further improve these applications of ITP.

PMID- 29018855
TI  - Mitochondrial-targeted multifunctional mesoporous Au@Pt nanoparticles for dual
      mode photodynamic and photothermal therapy of cancers.
AB  - In the conventional non-invasive cancer treatments, such as photodynamic therapy
      (PDT) and photothermal therapy (PTT), light irradiation is precisely focused on
      tumors to induce apoptosis via the generation of reactive oxygen species (ROS) or
      localized heating. However, overconsumption of oxygen and restricted diffusion
      distance of ROS limit the therapeutic effects on hypoxic tumors. Herein, we
      developed a platform for the rapid uptake of multifunctionalized Au@Pt
      nanoparticles (NPs) by mitochondria in cancer cells. The mesoporous Au@Pt
      nanoparticles were labeled with a cell-targeting ligand (folic acid), a
      mitochondria-targeting group (triphenylphosphine (TPP)), and a photosensitizer
      (Ce6). This led to significant improvement of the PDT efficacy due to an enhanced
      cellular uptake, an effective mitochondrial ROS burst, and a rapid intelligent
      release of oxygen. Moreover, Au@Pt NPs can convert laser radiation into heat,
      resulting in thermally induced cell damage. This nanosystem could be used as a
      dual-mode phototherapeutic agent for enhanced cancer therapy and molecular
      targets associated with disease progression. We achieved a mitochondria-targeted
      multifunctional therapy strategy (a combination of PDT and PTT) to substantially
      improve the therapeutic efficiency.

PMID- 29018856
TI  - Droplet impact on flowing liquid films with inlet forcing: the splashing regime.
AB  - The impact process of droplets falling obliquely on thin flowing films is studied
      using a high-speed imaging system with a focus on splashing. Frequency-forcing of
      the flow rate at the inlet is applied in order to form solitary waves prior to
      droplet impact. The outcomes associated with impact on targeted regions of the
      waves are examined; these include the capillary wave region preceding the large
      wave peak, the flat film region, and the wave hump region. The effect of varying
      the film flow rate, droplet size, and speed on the splashing regime for each of
      these regions is elucidated. The results are further compared with those
      associated with uncontrolled flowing films, and with quiescent films. The present
      work has demonstrated, for the first time, the contribution made by the spatial
      structure of waves to the outcome of droplet impact on flowing films.

PMID- 29018857
TI  - Plasmon mediated Fe-O in an octahedral site of cuprospinel by Cu NPs for
      photocatalytic hydrogen evolution.
AB  - Cu NPs (copper nanoparticles) were synthesized in situ on the surface of CuFe2O4
      (cuprospinel). The enhancement of the separation efficiency of photogenerated e
      /h+ and the catalytic quantum efficiency showed that the LSPR (local surface
      plasmon resonance) of Cu NPs facilitated the photocatalytic reaction activity of
      CuFe2O4. And due to the fact that CuFe2O4 was constructed with Cu-O in the
      tetrahedral site and Fe-O in the octahedral site, the results of DTG and Raman
      spectra after HER (hydrogen evolution reaction) displayed that the phase change
      of Fe-O in the octahedral site of CuFe2O4 took place during the HER process, and
      along with the peak of Fe2+ in XPS spectra after HER, which indicated that light
      activated Fe-O in the octahedral site was responsible for the photocatalytic
      process.

PMID- 29018858
TI  - Overall water splitting by photoelectrochemical cells consisting of
      (ZnSe)0.85(CuIn0.7Ga0.3Se2)0.15 photocathodes and BiVO4 photoanodes.
AB  - The design of photoelectrochemical (PEC) cell structures that mitigate challenges
      related to mass transfer is the key to achieving efficient hydrogen production. A
      PEC cell based on an integrated photoelectrode incorporating
      (ZnSe)0.85(CuIn0.7Ga0.3Se2)0.15 strips and BiVO4 strips exhibited 1.0% solar-to
      hydrogen energy conversion efficiency even without stirring the electrolyte
      solution.

PMID- 29018859
TI  - Constructing hierarchical porous nanospheres for versatile microwave response
      approaches: the effect of architectural design.
AB  - Owing to their immense potential in functionalized applications, tremendous
      interest has been devoted to the design and synthesis of nanostructures. The
      introduction of sufficient amount of microwaves into the absorbers on the premise
      that the dissipation capacity is strong enough remains a key challenge. Pursuing
      a general methodology to overcome the incompatibility is of great importance.
      There is widespread interest in designing the materials with specific
      architectures. Herein, the common absorber candidates were chosen to feature the
      hierarchical porous Fe3O4@C@Fe3O4 nanospheres. Due to the reduced skin effect
      (induced by low-conductivity Fe3O4 outer layer), multiple interfacial
      polarizations and scattering (due to the ternary hierarchical structures and
      nanoporous inner core) as well as the improved magnetic dissipation ability
      (because of multiple magnetic components), the material design enabled a
      promising microwave absorption performance. This study not only illustrates the
      primary mechanisms for the improved microwave absorption performance but also
      underscores the potential in designing the particular architectures as a strategy
      for achieving the compatibility characteristics.

PMID- 29018860
TI  - Competitive concurrence of surface wrinkling and dewetting of liquid crystalline
      polymer films on non-wettable substrates.
AB  - Polymeric thin films coated on non-wettable substrates undergo film
      instabilities, which are usually manifested as surface deformation in the form of
      dewetting or wrinkling. The former takes place in fluidic films, whereas the
      latter occurs in solid films. Therefore, there have rarely been reports of
      systems involving simultaneous deformations of dewetting and wrinkling. In this
      study, we propose polymeric thin films of liquid crystalline (LC) mesogens
      prepared on a non-wettable Si substrate and apply a treatment of plasma
      irradiation to form a thin polymerized layer at the surface. The resulting
      compressive stress generated in the surface region drives the formation of
      wrinkles, while at the same time, dipolar attraction between LC molecules induces
      competitive cohesive dewetting. Intriguing surface structures were obtained
      whereby dewetting-like hole arrays are nested inside the randomly propagated
      wrinkles. The structural features are readily controlled by the degree of surface
      cross-linking, hydrophilicity of the substrates, and the LC film thickness. In
      particular, dewetting of LC mesogens is observed to be restricted to occur at the
      trough regions of wrinkles, exhibiting the typical behavior of geometrically
      confined dewetting. Finally, wrinkling-dewetting mixed structures are separated
      from the substrate in the form of free standing films to demonstrate the
      potential applicability as membranes.

PMID- 29018861
TI  - Role of solvent properties of water in crowding effects induced by macromolecular
      agents and osmolytes.
AB  - Solvent properties of water in aqueous solutions of polyethylene glycols of
      various molecular weights, l-proline, betaine, and a series of chlorides of
      varied concentrations are assayed using three solvatochromic dyes. The properties
      include solvent dipolarity/polarizability, hydrogen bond donor acidity, and
      hydrogen bond acceptor basicity. These properties are also evaluated in mixtures
      of two polymers, polymer and osmolyte, and two osmolytes. It is shown that linear
      combinations of solvent dipolarity/polarizability and hydrogen bond donor acidity
      assayed in individual solutions of crowders strongly correlate with the effects
      of the crowders on the stability of various proteins and nucleic acids reported
      in the literature. The solvent properties of water in aqueous mixtures of two
      macromolecular crowders, two osmolytes, or mixtures of an osmolyte and a
      macromolecular crowder vary differently for various solvent properties. The
      overall effects of the two components in the mixture on a given solvent property
      of water may be additive, reduced or enhanced depending on the particular
      composition of the mixture. It is hypothesized that changes in the solvent
      properties of water are related to changes in the water hydrogen-bonding
      structuring. It is suggested that the observed crowder-induced changes in the
      solvent properties of water should be taken into account in theoretical
      considerations of crowding effects in biological systems.

PMID- 29018862
TI  - Supramolecular chirality of amphiphilic block copolymer films made through two
      steps: self-assembling first, and then solution coating.
AB  - Supramolecular chirality is achieved in amphiphilic block copolymer films made
      through two-step fabrication: self-assembling first and then solution coating.
      The amphiphilic block copolymer is composed of poly(N-isopropyl acrylamide)
      (pNIPAM) as hydrophilic segments and poly(methyl methacrylate) with chiral side
      groups as hydrophobic segments. The films fabricated by two steps show sensible
      circular dichroism (CD) signals around a wavelength of 200 nm. However, CD
      signals cannot be detected from films made by directly coating the solution of
      copolymers on the quartz surface. The CD signal at about 200 nm is from
      supramolecular arrangement of benzene units connected to the chiral group in the
      hydrophobic segment. This result is thought to be originated from the aggregation
      of the copolymer during the first step of the film forming process, and the
      corresponding investigation into factors affecting this process has been
      performed in this work. It is also found that the films fabricated by two steps
      can adsorb chiral small molecules enantioselectively, while the films obtained by
      coating the solution of copolymers directly have no such enatioselective
      adsorption ability.

PMID- 29018863
TI  - A unified understanding of the direct coordination of NO to first-transition-row
      metal centers in metal-ligand complexes.
AB  - The binding of nitric oxide (NO) to heme-proteins is an important biochemical
      process involved in a variety of physiological functions. Here, using hybrid
      density-functional calculations, we systematically investigate the adsorption of
      NO to first-transition-row metal centers in metal-ligand complexes. Through the
      comparative study for different transition metal (TM) centers, we provide a
      unified understanding of the microscopic interactions of NO with the TM centers
      and related chemical trends. We found that as the atomic number of the TM center
      increases, the binding strength of NO is largely reduced from 207 kJ mol-1 to
      near zero due to the low d-orbital energies for late TM centers. The
      intermolecular spin coupling between the localized spins at the TM center and the
      NO molecule is generally antiferromagnetic, except for the case of Sc. The spin
      spin coupling is determined in such a way to avoid the energy penalty associated
      with the electron occupation in the antibonding states of the NO-bound complex.
      The adsorption strength of NO is generally larger than of CO because the unpaired
      electron of NO occupies the associated bonding state.

PMID- 29018864
TI  - A cluster-based mesoporous Ti-MOF with sodalite supercages.
AB  - The cooperative assembly of a hexagonal column shaped [Ti6O6][iPrO]66+ cluster
      and rhomboid Cu2I2 dimers using isonicotinic acid results in an unprecedented
      three-dimensional (3D) highly crystalline cluster-based Ti-MOF that features both
      giant sodalite cages with an inner diameter of 2.8 * 3.2 nm2 and 3D open square
      channels.

PMID- 29018865
TI  - A zirconium metal-organic framework with an exceptionally high volumetric surface
      area.
AB  - A zirconium metal-organic framework (MOF), PCN-111, has been synthesized by using
      an elongated ditopic carboxylate linker, 4,4'-(buta-1,3-diyne-1,4
      diyl)dibenzoate. Single crystal X-ray diffraction characterization indicates that
      the noninterpenetrated microporous structure of PCN-111 is isoreticular to UIO
      MOFs with 12 connected Zr6O4(OH)4(CO2)12 clusters and a fcu topology. It was
      successfully activated through a solvent exchange with acetone followed by
      controlled evacuation and its gas sorption was reported. By using 77 K nitrogen
      adsorption isotherm and strictly applying three consistency criteria, the BET
      surface area for PCN-111 was calculated to be 4825 m2 g-1. Pore size distribution
      analysis suggests that the sizes of cavities contributing to nitrogen adsorption
      are predominately in the range of 15 to 20 A, which are in good agreement with
      the two polyhedral cages (15.6 and 20.2 A, respectively) in the single crystal X
      ray solved structure. Owing to its relatively high crystal density (0.42 g cm-3),
      the volumetric surface area for PCN-111 was calculated to be 2026 m2 cm-3. The
      value is among the highest of all the reported ultrahigh surface area MOF
      materials. The exceptionally high microporosity of PCN-111 has also been
      validated by comparison with the simulated nitrogen adsorption isotherm derived
      from multipurpose simulation code MUSIC.

PMID- 29018866
TI  - Are professional drivers less sleepy than non-professional drivers?
AB  - Objective It is generally believed that professional drivers can manage quite
      severe fatigue before routine driving performance is affected. In addition, there
      are results indicating that professional drivers can adapt to prolonged night
      shifts and may be able to learn to drive without decreased performance under high
      levels of sleepiness. However, very little research has been conducted to compare
      professionals and non-professionals when controlling for time driven and time of
      day. Method The aim of this study was to use a driving simulator to investigate
      whether professional drivers are more resistant to sleep deprivation than non
      professional drivers. Differences in the development of sleepiness (self
      reported, physiological and behavioral) during driving was investigated in 11
      young professional and 15 non-professional drivers. Results Professional drivers
      self-reported significantly lower sleepiness while driving a simulator than non
      professional drivers. In contradiction, they showed longer blink durations and
      more line crossings, both of which are indicators of sleepiness. They also drove
      faster. The reason for the discrepancy in the relation between the different
      sleepiness indicators for the two groups could be due to more experience to
      sleepiness among the professional drivers or possibly to the faster speed, which
      might unconsciously have been used by the professionals to try to counteract
      sleepiness. Conclusion Professional drivers self-reported significantly lower
      sleepiness while driving a simulator than non-professional drivers. However, they
      showed longer blink durations and more line crossings, both of which are
      indicators of sleepiness, and they drove faster.

PMID- 29018867
TI  - Changes in working conditions and major weight gain among normal- and overweight
      midlife employees.
AB  - Objectives We aimed to examine the association between changes in psychosocial
      working conditions and major weight gain among midlife women and men.
      Furthermore, we examined the associations separately among normal- and overweight
      participants. Methods We used survey data among employees of the City of
      Helsinki, Finland, from 2000-2002 (phase 1, N=8960), 2007 (phase 2, N=7332), and
      2012 (phase 3, N=6814), with a final study sample of 4369 participants. We
      examined changes in job strain, job demands, and job control from phase 1 to 2.
      We defined major weight gain as >=10% weight gain between phases 1 and 3 based on
      self-reported weight (kg). We performed logistic regression analysis adjusting
      for baseline age, marital status, and occupational class, stratifying by gender
      and by baseline body mass index. Results Job demands among both genders and job
      strain among women was associated with major weight gain. Furthermore, increased
      job demands [odds ratio (OR) 1.52, 95% CI 1.05-2.20] or increased job strain (OR
      1.53, 95% CI 1.11-2.11) was associated with major weight gain among overweight
      women. Normal-weight men reporting decreased job demands (OR 4.11, 95% CI 1.48
      11.40) and overweight men reporting increasing job demands (OR 2.93, 95% CI 1.26
      6.82) exhibited higher odds of major weight gain. Conclusions Associations
      between working conditions and weight gain appeared primarily weak. Our study
      suggests that overweight individuals might be at a higher risk of weight gain
      when facing psychosocial strain in the workplace.

PMID- 29018870
TI  - Correction to: Expanding Diversity and Common Goal of Regulatory T and B Cells.
      I: Origin, Phenotype, Mechanisms.
AB  - The original article has been published without acknowledgment section. The
      acknowledgement section is given below for your reading.

PMID- 29018868
TI  - Differential gene regulatory networks in development and disease.
AB  - Gene regulatory networks, in which differential expression of regulator genes
      induce differential expression of their target genes, underlie diverse biological
      processes such as embryonic development, organ formation and disease
      pathogenesis. An archetypical systems biology approach to mapping these networks
      involves the combined application of (1) high-throughput sequencing-based
      transcriptome profiling (RNA-seq) of biopsies under diverse network perturbations
      and (2) network inference based on gene-gene expression correlation analysis. The
      comparative analysis of such correlation networks across cell types or states,
      differential correlation network analysis, can identify specific molecular
      signatures and functional modules that underlie the state transition or have
      context-specific function. Here, we review the basic concepts of network biology
      and correlation network inference, and the prevailing methods for differential
      analysis of correlation networks. We discuss applications of gene expression
      network analysis in the context of embryonic development, cancer, and congenital
      diseases.

PMID- 29018871
TI  - [Pacemaker, defibrillator and co : Perioperative handling of cardiac implantable
      electronic devices].
AB  - The number of patients treated with cardiac implantable electronic devices (CIED)
      is continously increasing. Knowledge of the medical indications and technical
      mode of functioning of these devices is a basic prerequisite for the safe
      perioperative care of this patient cohort. The CIEDs are subjected to a multitude
      of disturbing influences in the perioperative setting. This can result in
      potentially dangerous complications, such as exit block and oversensing. The safe
      performance of interventions is possible as long as some basic rules are
      followed. An interdisciplinary approach involving all participating disciplines
      is necessary in order to adequately deal with the high demands placed on the
      logistics.

PMID- 29018872
TI  - [Quality criteria for minimally invasive esophagectomy - a register analysis].

PMID- 29018873
TI  - The treatment of perilunate ligament injuries in multiply injured patients.
AB  - PURPOSE: Perilunate injuries are rare, severe injuries of the carpus. They can
      present as isolated injuries or in the poly-traumatised patient. This is the
      first documented series of these injuries treated in a Major Trauma Centre. The
      aims were to assess the management, treatment algorithm and outcomes, of
      perilunate injuries in our department, review whether concomitant polytrauma
      affected those outcomes and identify if delay to definitive treatment had a
      significant effect on overall outcome. METHODS: Perilunate injuries admitted to
      the Royal London Hospital between Oct 2011 and March 2016 were identified. All
      definitive surgical procedures were performed by the senior author; hand
      therapists supervised patient rehabilitation. Outcomes were assessed by Mayo
      Wrist and QuickDASH scores. RESULTS: We identified 23 perilunate injuries (22
      patients). There was an associated nerve injury in 10 cases with other system
      injuries present in 12 cases. At final review, the mean carpal height ratio was
      0.56, Mayo Wrist score was 81 and QuickDASH score was 16.4. There were no
      differences when comparing the outcomes of patients who had early against those
      with more delayed definite treatment or when comparing patients with isolated
      wrist injuries against polytrauma patients. CONCLUSION: Satisfactory outcomes can
      be achieved, even in the presence of other injuries, if initial treatment is
      prompt and follows a clear management protocol. Prompt early reduction and
      neurological decompression followed by subsequent accurate definitive fixation
      leads to good outcomes. A delay of definitive fixation of up to 18 days does not
      appear to have a deleterious effect on outcome.

PMID- 29018869
TI  - Molecular components and polarity of radial glial cells during cerebral cortex
      development.
AB  - Originating from ectodermal epithelium, radial glial cells (RGCs) retain apico
      basolateral polarity and comprise a pseudostratified epithelial layer in the
      developing cerebral cortex. The apical endfeet of the RGCs faces the fluid-filled
      ventricles, while the basal processes extend across the entire cortical span
      towards the pial surface. RGC functions are largely dependent on this polarized
      structure and the molecular components that define it. In this review, we will
      dissect existing molecular evidence on RGC polarity establishment and during
      cerebral cortex development and provide our perspective on the remaining key
      questions.

PMID- 29018876
TI  - [Report of the molecular pathology working group].

PMID- 29018877
TI  - Correction to: Digestive system in psoriasis: an update.
AB  - In the original publication, the data labels are incorrect in Fig. 3. The
      corrected Fig. 3 is given here.

PMID- 29018874
TI  - Flavocoxid exerts a potent antiviral effect against hepatitis B virus.
AB  - INTRODUCTION: Flavocoxid is a proprietary blend of two flavonoids, baicalin and
      catechin, and recent evidence has shown that bioflavonoids may exert antiviral
      activities. The potential antiviral activity of Flavocoxid against hepatitis B
      virus (HBV) was evaluated. Additionally, it was investigated if Flavocoxid used
      in combination with Entecavir could potentiate its anti-HBV activity. MATERIALS
      AND METHODS: Hepatoma cells replicating HBV were treated with Flavocoxid, or
      Entecavir alone or in combination for up to 5 days. Viral replicative
      intermediates, transcripts, and cccDNA levels were evaluated in HBV-replicating
      cells by real-time PCR, Southern and Northern blotting. Expression profiling was
      performed using TaqMan low-density arrays. RESULTS: Flavocoxid treatment induced
      a reduction of HBV replicative intermediates, the amount of transcripts, and
      HBsAg levels. Flavocoxid and Entecavir combination therapy further decreased the
      amount of HBV replicative intermediates, compared to Flavocoxid alone.
      Importantly, Flavocoxid alone or in combination with Entecavir also induced a
      reduction of cccDNA. Gene-expression analysis showed that Flavocoxid activates
      type I IFNs-signaling and dampens the HBV-induced inflammatory response.
      CONCLUSIONS: Flavocoxid inhibits HBV replication by targeting multiple steps of
      viral life cycle. These results indicate that the antiviral activity of Entecavir
      is potentiated by Flavocoxid, suggesting that this medical food might be
      considered as an adjuvant for anti-HBV therapy.

PMID- 29018875
TI  - Human neutrophils are targets to paracoccin, a lectin expressed by
      Paracoccidioides brasiliensis.
AB  - OBJECTIVE AND DESIGN: Paracoccin (PCN), a lectin expressed by Paracoccidioides
      brasiliensis (Pb), is known to exert activities on the fungal biology, as well as
      different immune cells of myeloid origin. The aim of this study was to
      investigate the direct interaction of the recombinant form of the lectin (rPCN)
      with neutrophils, a neglected area. MATERIALS OR SUBJECTS: Freshly isolated human
      neutrophils from healthy donors were used. TREATMENT: Neutrophils were incubated
      with rPCN in vitro. METHODS: After the treatment, the production of reactive
      oxygen species (ROS), DNA release, IL-8, TNF, IFN-gamma, IL-10, IL-12p40, TGF
      beta and IL-1beta production, fungicidal ability, apoptosis and de novo protein
      synthesis was determined. RESULTS: rPCN was found to induce ROS production as
      well as DNA release. Using the ROS inhibitor, diphenyleneiodium, both ROS
      production and DNA release were significantly inhibited. In addition, rPCN was
      found to induce IL-8 and IL1-beta production, inhibit apoptosis and induce de
      novo protein synthesis. Addition of cycloheximide, a protein synthesis inhibitor,
      drastically reversed the antiapoptotic effect of rPCN. Finally, the ability to
      kill Pb yeasts by human neutrophils was significantly increased after rPCN
      stimulation. CONCLUSIONS: rPCN can alter the biology of human neutrophils
      increasing their fungicidal ability. Moreover, the ability of rPCN to increase
      DNA release and to induce suppression of neutrophil apoptosis occurs by a ROS-
      and de novo protein synthesis-dependent mechanism, respectively.

PMID- 29018878
TI  - Investigating Internalization and Intracellular Trafficking of GPCRs: New
      Techniques and Real-Time Experimental Approaches.
AB  - The ability to regulate the interaction between cells and their extracellular
      environment is essential for the maintenance of appropriate physiological
      function. For G protein-coupled receptors (GPCRs), this regulation occurs through
      multiple mechanisms that provide spatial and temporal control for signal
      transduction. One of the major mechanisms for GPCR regulation involves their
      endocytic trafficking, which serves to internalize the receptors from the plasma
      membrane and thereby attenuate G protein-dependent signaling. However, there is
      accumulating evidence to suggest that GPCRs can signal independently of G
      proteins, as well as from intracellular compartments including endosomes. It is
      in this context that receptor internalization and intracellular trafficking have
      attracted renewed interest within the GPCR field. In this chapter, we will review
      the current understanding and methodologies that have been used to investigate
      internalization and intracellular signaling of GPCRs, with a particular focus on
      emerging real-time techniques. These recent developments have improved our
      understanding of the complexities of GPCR internalization and intracellular
      signaling and suggest that the broader biological relevance and potential
      therapeutic implications of these processes remain to be explored.

PMID- 29018883
TI  - Author Correction: Why free choices take longer than forced choices: evidence
      from response threshold manipulations.
AB  - The authors regret that some errors that had been addressed during the proofing
      process were not corrected by the publisher. Most of these errors are of a
      stylistic nature and do not change the substance of the article. Please note,
      however, that the corresponding author's e-mail address is christoph.naefgen@uni
      tuebingen.de. We apologize for any inconvenience caused by this.

PMID- 29018884
TI  - Pen Torch Transillumination: Difficult Venepuncture Made Easy: Reply.

PMID- 29018886
TI  - Focus on nutrition and glucose control in the intensive care unit: recent
      advances and debates.

PMID- 29018887
TI  - [Prognostic importance of resection margins in multiple colorectal liver
      metastases].

PMID- 29018885
TI  - Size and shape of the associations of glucose, HbA1c, insulin and HOMA-IR with
      incident type 2 diabetes: the Hoorn Study.
AB  - AIMS/HYPOTHESIS: Glycaemic markers and fasting insulin are frequently measured
      outcomes of intervention studies. To extrapolate accurately the impact of
      interventions on the risk of diabetes incidence, we investigated the size and
      shape of the associations of fasting plasma glucose (FPG), 2 h post-load glucose
      (2hPG), HbA1c, fasting insulin and HOMA-IR with incident type 2 diabetes
      mellitus. METHODS: The study population included 1349 participants aged 50-75
      years without diabetes at baseline (1989) from a population-based cohort in
      Hoorn, the Netherlands. Incident type 2 diabetes was defined by the WHO 2011
      criteria or known diabetes at follow-up. Logistic regression models were used to
      determine the associations of the glycaemic markers, fasting insulin and HOMA-IR
      with incident type 2 diabetes. Restricted cubic spline logistic regressions were
      conducted to investigate the shape of the associations. RESULTS: After a mean
      follow-up duration of 6.4 (SD 0.5) years, 152 participants developed diabetes
      (11.3%); the majority were screen detected by high FPG. In multivariate adjusted
      models, ORs (95% CI) for incident type 2 diabetes for the highest quintile in
      comparison with the lowest quintile were 9.0 (4.4, 18.5) for FPG, 6.1 (2.9, 12.7)
      for 2hPG, 3.8 (2.0, 7.2) for HbA1c, 1.9 (0.9, 3.6) for fasting insulin and 2.8
      (1.4, 5.6) for HOMA-IR. The associations of FPG and HbA1c with incident diabetes
      were non-linear, rising more steeply at higher values.
      CONCLUSIONS/INTERPRETATION: FPG was most strongly associated with incident
      diabetes, followed by 2hPG, HbA1c, HOMA-IR and fasting insulin. The strong
      association with FPG is probably because FPG is the most frequent marker for
      diabetes diagnosis. Non-linearity of associations between glycaemic markers and
      incident type 2 diabetes should be taken into account when estimating future risk
      of type 2 diabetes based on glycaemic markers.

PMID- 29018888
TI  - [Non-melanoma skin cancer : Pathogenesis, prevalence and prevention].
AB  - Non-melanoma skin cancer (NMSC) is the most common malignancy of the light
      skinned population with an enormous socioeconomic impact. Historically known as
      incurable under the term noli me tangere (transl. do not touch me), today various
      non-melanocytic cutaneous neoplasms are grouped as NMSC. The most common of
      these, basal cell carcinoma, squamous cell carcinoma and actinic keratoses as
      carcinomas in situ, are increasingly called keratinocyte carcinoma. Today, the
      pathogenesis and risk factors of NMSC are relatively well understood, which has
      led to multiple treatment options, the recognition of NMSC as an occupational
      disease in Germany and a variety of prevention approaches. Although there is
      largely general consensus in the dermatological world, knowledge of affected high
      risk groups in NMSC and prevention is still very low. The development of target
      group-oriented awareness and prevention campaigns are therefore urgently needed.

PMID- 29018889
TI  - [Oculocutaneous and ocular albinism].
AB  - Albinism can be divided into oculocutaneous albinism (OCA) and ocular albinism
      (OA). In the differential diagnostics these can be distinguished from rarer
      syndromes with partial albinism, which are frequently associated with
      susceptibility to infections and neurological symptoms. The OCA is an autosomal
      recessive inherited disease of melanin biosynthesis, which leads to complete or
      partial loss of melanin in the skin, hair follicles and eyes. Of the seven
      currently known subtypes (OCA 1-7), four are well-characterized (OCA 1-4). These
      are based on gene mutations, which code for tyrosinase, a key enzyme in melanin
      synthesis and for further proteins. These play an important role in the catalytic
      activity of tyrosinase and the structure and function of melanosomes. In the
      presence of these subtypes, the clinical symptoms and the course of the disease
      show a pronounced variability, especially in the type and extent of pigmentation
      of the skin and hair as well as the severity of eye involvement, which makes the
      phenotypic classification difficult. Treatment priorities are a consistent
      protection from UV light for prophylaxis against skin cancer and regular
      preventive investigations. The ocular alterations typical for albinism
      necessitate timely diagnostics and care by institutions specialized in
      ophthalmology. Novel strategies for systemic treatment of subtypes of albinism
      are in preclinical testing. The OA without skin involvement shows X-linked
      inheritance, is much rarer and is characterized by reduced pigmentation of the
      retina and iris, nystagmus and macular hypoplasia, sometimes with substantial
      loss of visual acuity. The typical ocular symptoms of OA can be manifested to a
      varying extent in all forms of OCA.

PMID- 29018890
TI  - [Magnetic resonance imaging findings after shoulder surgery: What the radiologist
      needs to know].
AB  - Even primary diagnostic evaluation of the shoulder is a challenge for
      radiologists. Many imaging findings that definitely indicate abnormal findings in
      the untreated shoulder should be evaluated carefully in postoperative patients.
      Artifacts caused by implants or metal abrasion pose considerable problems in
      postoperative magnetic resonance imaging (MRI). Classic approaches to minimizing
      artifacts caused by foreign bodies include using turbo spin echo sequences,
      increasing bandwidth, and reducing voxel size. In recent years, several vendors
      have developed dedicated pulse sequences for reducing metal artifacts. Different
      postoperative imaging findings will be encountered, depending on the kind of
      surgery done. This review article describes typical postoperative MRI findings,
      focusing on subacromial decompression, reconstruction of the rotator cuff, labrum
      procedures, and biceps tenodesis.

PMID- 29018891
TI  - [Depression and anxiety : Prevalence among ENT outpatients].
AB  - BACKGROUND: Few data exist on the prevalence of comorbid mental disorders among
      ENT patients. This investigation aimed to assess the prevalence of two disorders
      frequent in our society, namely depression and anxiety, in patients of an ENT
      outpatient clinic. PATIENTS AND METHODS: During a 2-week period, 101 consecutive
      patients were interviewed with the Beck Depression Inventory-II (BDI II) and Beck
      Anxiety Inventory (BAI) screening aids. RESULTS: Of 97 evaluated tests, 38%
      contained indications of a psychiatric problem or mental comorbidity. The
      proportion of moderate and severe depressive syndromes, anxiety disorders, and
      combined disorders was only 11.3%. There were no significant differences between
      genders or in terms of acute vs. chronic ENT diseases. The highest frequency of
      pathological test results was observed in the group of patients with
      cochleovestibular disorders. An astoundingly high number of conspicuous test
      results were seen in patients with trivial diseases and disorders, as well as
      among those with chronic obstructive disorders of the nose and sinuses.
      CONCLUSION: The finding of a considerable prevalence of psychiatric comorbidities
      among ENT patients represents important information for the treating physician.
      BDI II and BAI were found to be reliable and easy to apply in the outpatient
      clinic.

PMID- 29018892
TI  - Novel treatment opportunities for sulfur mustard-related cancers: genetic and
      epigenetic perspectives.
AB  - Sulfur mustard (SM), also known as mustard gas, is a chemical weapon which by now
      has been used in many wars. The most concerning SM toxic effect is probable
      carcinogenicity. In this study, the genetic and epigenetic mechanisms of SM
      carcinogenicity, by focusing on treatment of SM-associated malignancies,
      particularly gene therapeutics, cancer vaccines, and epigenetic medications, have
      been criticized. The required data were collected through an organized search on
      valid scientific databases. For SM carcinogenicity due to acute or chronic
      exposure, the entire original and review articles were evaluated. In addition,
      studies on the therapeutic effects of available genetic and epigenetic
      medications were included. Currently, four gene therapeutics, two cancer vaccines
      with genetic bases, and seven epigenetic medications are available for cancer
      treatment. Genetic and epigenetic cancer treatments including Gendicine, Imlygic,
      Provenge, Cimavax-EGF, Azacitidine, Vorinostat, Romidepsin, and Belinostat will
      yield outstanding benefits for SM-exposed patients who suffer from cancer.

PMID- 29018894
TI  - Abstinence-induced withdrawal severity among adolescent smokers with and without
      ADHD: disentangling effects of nicotine and smoking reinstatement.
AB  - RATIONALE: Individuals with attention deficit hyperactivity disorder (ADHD) start
      smoking earlier, are more likely to progress to nicotine dependence, and have a
      more difficult time quitting smoking compared to their non-ADHD peers. Little is
      known about the underlying behavioral mechanisms associated with this increased
      risk, particularly at the adolescent stage. OBJECTIVE: This study aimed to assess
      the effects of overnight nicotine abstinence and smoking reinstatement on
      subjective withdrawal states in adolescent smokers with and without ADHD.
      METHODS: Adolescent daily smokers (27 with ADHD and 17 without ADHD) completed
      three experimental sessions: (1) a placebo patch followed by smoking a nicotine
      cigarette, (2) placebo patch followed by smoking a nicotine-free cigarette, and
      (3) nicotine patch followed by smoking a nicotine-free cigarette. Subjects
      abstained overnight before each session, and patches were administered 45 min
      before smoking. The primary outcome measure was a smoking withdrawal symptom
      questionnaire. RESULTS: ADHD smokers experienced greater difficulty concentrating
      and impatience/restlessness during abstinence than non-ADHD smokers. Smoking a
      cigarette improved abstinence-induced difficulty concentrating and restlessness,
      regardless of its nicotine content, and regardless of whether transdermal
      nicotine was received or not. CONCLUSIONS: Thus, sensorimotor aspects of smoking,
      rather than nicotine itself, appeared to relieve withdrawal. Although ADHD
      smokers report greater withdrawal symptoms than non-ADHD smokers, they responded
      strongly to the sensorimotor aspects of smoking during withdrawal. These findings
      suggest that even lighter, adolescent smokers with ADHD are vulnerable to smoking
      progression through altered smoking abstinence and withdrawal relief processes.

PMID- 29018893
TI  - Sex-specific attenuation of impulsive action by progesterone in a go/no-go task
      for cocaine in rats.
AB  - RATIONALE: Previous work indicated that progesterone (PRO) reduced impulsive
      choice for cocaine in female but not male rats (Smethells et al.
      Psychopharmacology 233:2999-3008, 2016). Impulsive action, typically measured by
      responding for a reinforcer during a signaled period of nonavailability of
      natural reinforcers, predicts initiation and escalation of drug use in animals
      and humans. The present study examined impulsive action for cocaine using PRO in
      male and female rats trained on a go/no-go task. OBJECTIVE: Rats were trained on
      a go/no-go task to respond for cocaine infusions (0.4 mg/kg/inf). During the "go"
      component, responding was reinforced on a VI 30-s schedule, whereas during the
      "no-go" component, withholding a response was reinforced on a differential
      reinforcement of other behavior (DRO) 30-s schedule. A response during the no-go
      component resets the DRO timer and served as a measure of impulsive action. After
      baseline responding was established, rats were pretreated with vehicle (VEH) or
      PRO (0.5 mg/kg), and DRO resets and responding during the go component for
      cocaine were compared in males vs. females. RESULTS: DRO resets were
      significantly lower following PRO treatment compared to VEH in female, but not
      male, rats. Response rates and overall infusions during the go component were not
      significantly altered by PRO in either females or males. CONCLUSION: Treatment
      with PRO resulted in a sex-specific reduction in impulsive action for cocaine,
      while not affecting cocaine self-administration.

PMID- 29018895
TI  - Production of indoleacetic acid by strains of the epiphytic bacteria Neptunomonas
      spp. isolated from the red alga Pyropia yezoensis and the seagrass Zostera
      marina.
AB  - Neptunomonas sp. BPy-1 is an epiphytic bacterium isolated from in vitro culture
      of the red alga Pyropia yezoensis. It uses ethanol as a sole carbon source and
      promotes the growth of host alga. A related bacterium, Neptunomonas sp. BZm-1,
      was isolated from leaves of Zostera marina found in the Yatsushiro Sea (Japan).
      BZm-1 showed 99% 16S rRNA sequence identity with Neptunomonas sp. BPy-1. Similar
      to BPy-1, BZm-1 grew in artificial seawater (ASW) medium containing ethanol or
      butanol. When thalli were treated with a multi-enzyme cleaner, the growth of
      treated thalli was retarded, but the addition of BZm-1 to the medium promoted
      growth. To explore the benefits of epiphytic bacteria, indoleacetic acid (IAA)
      production by isolated bacteria was examined under conditions of limited
      nutrients. Salkowski assays and GC-MS analysis revealed that both BZm-1 and BPy-1
      excreted IAA during growth in ASW medium containing glucose or ethanol in the
      presence of tryptophan. In ASW medium containing tryptophan but lacking a carbon
      source, neither isolate grow, but produced IAA. ASW medium includes nitrate as
      the sole nitrogen source. In the absence of carbon source, different nitrogen
      forms in the presence of tryptophan did not affect IAA production by the two
      isolates. These findings indicate that IAA production by the two isolates is
      strictly dependent on tryptophan but less affected by carbon and nitrogen
      sources. Based on the different origins of BPy-1 and BZm-1, this mode of IAA
      production seems to be conserved among relatives of BPy-1.

PMID- 29018896
TI  - Hypericum perforatum extract modulates cortical plasticity in humans.
AB  - BACKGROUND: Hypericum perforatum (HYP) extract is one of the most commonly used
      complementary alternative medicines (CAMs) for the treatment of mild-to-moderate
      depression. Non-invasive brain stimulation protocols can be used to investigate
      the effect of psychoactive substances on the human brain. In this study, we
      explored the effect of a single dose of HYP extract (WS 5570) intake on
      corticospinal excitability and plasticity in humans. METHODS: Twenty-eight
      healthy subjects were required to intake 900 mg of either HYP extract or placebo.
      Cortical excitability was assessed using single and paired transcranial magnetic
      stimulation (TMS). The electrophysiological parameters of motor threshold,
      recruitment of motor-evoked potentials (MEPs), cortical silent period (CSP),
      short interval intracortical inhibition (SICI), and intracortical facilitation
      (ICF) were tested before and 2 and 5 h after the oral intake. Spinal and
      neuromuscular excitability and peripheral nerve excitability were measured by F
      response and M-wave. Cortical plasticity was induced using transcranial direct
      current stimulation (tDCS). Subjects received either HYP extract or placebo
      before anodal and cathodal tDCS of the primary motor cortex. Plasticity was
      assessed by MEP amplitudes. RESULTS: HYP extract reversed cathodal tDCS-induced
      long-term depression (LTD)-like plasticity into facilitation, as compared to
      placebo. HYP extract did not have a significant effect on anodal tDCS-induced
      plasticity and TMS measures of motor cortex and spinal/neuromuscular
      excitability. CONCLUSIONS: Our findings suggest that a single oral dose of HYP
      extract modulates cortical plasticity in healthy subjects and provide new insight
      into its possible mechanism of action in humans.

PMID- 29018897
TI  - Lack of Evidence that Soluble Urate Directly Influences Bone Remodelling: A
      Laboratory and Clinical Study.
AB  - INTRODUCTION: Numerous observational studies have reported that serum urate
      concentration positively correlates with bone density and reduced risk of
      fractures. The aim of this study was to examine whether soluble urate directly
      influences bone remodelling. METHODS: In laboratory studies, the in vitro effects
      of soluble urate were examined in osteoclast, osteoblast and osteocyte assays at
      a range of urate concentrations consistent with those typically observed in
      humans (up to 0.70 mmol/L). The clinical relevance of the in vitro assay findings
      was assessed using serial procollagen-1 N-terminal propeptide (P1NP) and Month 12
      bone density data from a randomised controlled trial of allopurinol dose
      escalation in people with gout. RESULTS: Addition of urate in the RAW264.7 cell
      osteoclastogenesis assay led to small increases in osteoclast formation (ANOVA p
      = 0.018), but no significant difference in bone resorption. No significant
      effects on osteoclast number or activity were observed in primary cell
      osteoclastogenesis or resorption assays. Addition of urate did not alter
      viability or function in MC3T3-E1 pre-osteoblast, primary human osteoblast, or
      MLO-Y4 osteocyte assays. In the clinical trial analysis, reducing serum urate
      over a 12 month period by allopurinol dose escalation did not lead to significant
      changes in P1NP or differences in bone mineral density. CONCLUSION: Addition of
      soluble urate at physiological concentrations does not influence bone remodelling
      in vitro. These data, together with clinical trial data showing no effect of
      urate-lowering on P1NP or bone density, do not support a direct role for urate in
      influencing bone remodelling.

PMID- 29018898
TI  - Authors reply to "No, we are not-we keep forgetting the right ventricle".

PMID- 29018899
TI  - Langer's axillary arch: a frequent but rarely discussed anatomical variant in the
      radiologic literature.
AB  - The axillopectoral muscle is a rarely discussed variant of muscular anatomy of
      the axilla, with various clinical implications. We report a case of a 7-year-old
      girl with multiple genetic and developmental abnormalities who presented with
      asymmetrical right axillary bulging of unknown etiology. MRI demonstrated a small
      accessory axillary muscle, known as Langer's axillary arch and/or the
      axillopectoral muscle. Other than soft-tissue asymmetry, the patient experienced
      no additional related symptoms. However, this is an important variant to be aware
      of, as it can easily be discovered on imaging and may be a causative agent for
      various upper extremity symptoms that may resolve with appropriate recognition
      and surgical intervention.

PMID- 29018900
TI  - Reliable quantification of 1,2-dihydroxynaphthalene in urine using a conjugated
      reference compound for calibration.
AB  - After environmental and occupational exposure to naphthalene, 1,2
      dihydroxynaphthalene (1,2-DHN) was shown to be one major metabolite in human
      naphthalene metabolism. However, the instability of free 1,2-DHN complicates the
      reliable determination of this promising biomarker in urine. To solve this
      stability problem, glucuronide conjugates of 1,2-DHN and the corresponding
      isotopically labelled D6-1,2-dihydroxynaphthalene (D6-1,2-DHN) were synthesised
      and applied as reference material and internal standard in a gas chromatographic
      tandem mass spectrometric (GC-MS/MS) method. The determination of 1- and 2
      naphthol (1-MHN, 2-MHN) was included in the procedure to enable a comprehensive
      assessment of naphthalene metabolism and exposure. The results of the validation
      showed a high reliability and sensitivity of the method. The detection limits
      range from 0.05 to 0.16 MUg/L. Precision and repeatability were determined to
      range from 1.4 to 6.6% for all parameters. The simultaneous determination of 1-
      and 2-MHN as additional parameters besides 1,2-DHN enables the application of the
      method for further metabolism and kinetic studies on naphthalene. The use of
      glucuronide-derivative reference substances and the application of structurally
      matched isotopic-labelled internal standards for each substance guarantee a
      reliable quantification of the main naphthalene metabolites 1,2-DHN and 1- and 2
      MHN. Graphical abstract Reliable quantification of 1,2-dihydroxynaphthalene in
      urine using a conjugated reference compound for calibration.

PMID- 29018901
TI  - Rapid determination of the emerging contaminant oxypurinol in surface water using
      solid phase extraction followed by ultra high-performance liquid chromatography
      with fluorescence detection.
AB  - A method has been developed for the trace analysis of oxypurinol that is
      considered as an active pharmaceutical ingredient and an emerging environmental
      contaminant. The method achieved the identification and quantification of
      oxypurinol in surface water samples utilizing solid phase extraction and ultra
      high-performance liquid chromatography with diode array and fluorescence
      detection for the first time. Four principal parameters of solid phase extraction
      were optimized to obtain maximum extraction efficiency. Under the isocratic
      elution of methanol/water (5:95, v/v) and the excitation/emission wavelength of
      254/359 nm, a rapid determination was achieved in 2.0 min with good linearity of
      1.05-351 MUg/L (coefficient of determination above 0.9998). The limit of
      detection and method detection limit were 0.210 MUg/L and 1.34 ng/L,
      respectively. Precision of the method was evaluated and a relative standard
      deviation value of 3.3% was obtained for analyses of six replicate spiking blank
      samples (200 mL, 176 ng/L) according to the overall proposed procedure. The
      method showed a great anti-interference ability and average spiked recoveries of
      oxypurinol in five surface water samples were in the range of 94.5-111%. The
      ability of the method to detect and correctly identify oxypurinol can
      significantly promote investigation on the occurrence of oxypurinol in water and
      its potential (eco-)toxicological effects. Graphical abstract Quantification of
      the emerging contaminant oxypurinol in s urface water using SPE/UHPLC-FLD.

PMID- 29018902
TI  - The P/N (Positive-to-Negative Links) Ratio in Complex Networks-A Promising In
      Silico Biomarker for Detecting Changes Occurring in the Human Microbiome.
AB  - Relatively little progress in the methodology for differentiating between the
      healthy and diseased microbiomes, beyond comparing microbial community
      diversities with traditional species richness or Shannon index, has been made.
      Network analysis has increasingly been called for the task, but most currently
      available microbiome datasets only allows for the construction of simple species
      correlation networks (SCNs). The main results from SCN analysis are a series of
      network properties such as network degree and modularity, but the metrics for
      these network properties often produce inconsistent evidence. We propose a simple
      new network property, the P/N ratio, defined as the ratio of positive links to
      the number of negative links in the microbial SCN. We postulate that the P/N
      ratio should reflect the balance between facilitative and inhibitive interactions
      among microbial species, possibly one of the most important changes occurring in
      diseased microbiome. We tested our hypothesis with five datasets representing
      five major human microbiome sites and discovered that the P/N ratio exhibits
      contrasting differences between healthy and diseased microbiomes and may be
      harnessed as an in silico biomarker for detecting disease-associated changes in
      the human microbiome, and may play an important role in personalized diagnosis of
      the human microbiome-associated diseases.

PMID- 29018903
TI  - Clinical Significance of DXA and HR-pQCT in Autosomal Dominant Osteopetrosis (ADO
      II).
AB  - The main hallmark of high bone mass (HBM) disorders is increased bone mineral
      density, potentially visible in conventional radiographs and quantifiable by
      other radiographic methods. While one of the most common forms of HBM is CLCN7
      related autosomal dominant osteopetrosis type II (ADO II), there is no consensus
      on diagnostic thresholds. We therefore wanted to assess whether CLCN7
      osteopetrosis patients differ from benign HBM cases in terms of (1) bone mineral
      density, (2) bone structure, and (3) microarchitectural abnormalities. 16
      patients meeting the criteria of HBM (DXA T/Z-score >= 2.5 at all sites) were
      included in this retrospective study. Osteologic assessment using dual-energy X
      ray absorptiometry (DXA), high-resolution peripheral quantitative computed
      tomography (HR-pQCT), and serum analyses was performed. The presence of CLCN7
      and/or other HBM gene mutations affecting bone mass were tested using a custom
      designed bone panel. While a DXA threshold for ADO II could be implemented (DXA Z
      score >= + 6.0), the differences in bone microarchitecture were of lesser extent
      compared to the benign HBM group. All adult patients with ADO II suffered from
      elevated fracture rates independent from Z-score. In HR-pQCT, structural
      alterations, such as bone islets were found only inconsistently. In cases of HBM,
      a DXA Z-score >= 6 may be indicative for an inheritable HBM disorder, such as ADO
      II. Microarchitectural bone alterations might represent local microfracture
      repair or accumulation of cartilage remnants due to impaired osteoclast function,
      but seem not to be correlated with fracture risk.

PMID- 29018904
TI  - Kyphosis and incident falls among community-dwelling older adults.
AB  - : Hyperkyphosis commonly affects older persons and is associated with morbidity
      and mortality. Many have hypothesized that hyperkyphosis increases fall risk.
      Within this prospective study of older adults, kyphosis was significantly
      associated with incident falls over 1 year. Measures of hyperkyphosis could
      enhance falls risk assessments during primary care office visits. INTRODUCTION:
      To determine the association between four measures of kyphosis and incident and
      injurious falls in older persons. METHODS: Community-dwelling adults aged 65 and
      older (n = 72) residing in southern California were invited to participate in a
      prospective cohort study. Participants had kyphosis assessed four ways. Two
      standing measures included a flexicurve ruler placed against the back to derive a
      kyphotic index and the Debrunner kyphometer, a protractor used to measure the
      kyphotic angle in degrees. Two lying measures included the blocks method (number
      of 1.7 cm blocks needed to achieve a neutral head position while lying supine)
      and traditional Cobb angle calculation derived from DXA based lateral vertebral
      assessment. Baseline demographic, clinical, and other health information
      (including a timed up and go (TUG) test) were assessed at a clinic visit.
      Participants were followed monthly through email or postcard for 1 year, with
      falls outcomes confirmed through telephone interview. RESULTS: Mean age was 77.8
      (+/- 7.1) among the 52 women and 20 men. Over 12 months, 64% of participants
      experienced at least one incident fall and 35% experienced an injurious fall.
      Each standard deviation increase in kyphosis resulted in more than doubling the
      adjusted odds of an incident fall, even after adjusting for TUG. Odds of
      injurious falls were less consistent across measures; after adjusting for TUG,
      only the blocks method was associated with injurious falls. CONCLUSIONS: Each
      kyphosis measure was independently associated with incident falls. Findings were
      inconsistent for injurious falls; the blocks measure suggested the strongest
      association. If these findings are replicated, the blocks measure could be
      incorporated into office visits as a quick and efficient tool to identify
      patients at increased fall risk.

PMID- 29018905
TI  - CYP109E1 is a novel versatile statin and terpene oxidase from Bacillus
      megaterium.
AB  - CYP109E1 is a cytochrome P450 monooxygenase from Bacillus megaterium with a
      hydroxylation activity for testosterone and vitamin D3. This study reports the
      screening of a focused library of statins, terpene-derived and steroidal
      compounds to explore the substrate spectrum of this enzyme. Catalytic activity of
      CYP109E1 towards the statin drug-precursor compactin and the prodrugs lovastatin
      and simvastatin as well as biotechnologically relevant terpene compounds
      including ionones, nootkatone, isolongifolen-9-one, damascones, and beta
      damascenone was found in vitro. The novel substrates induced a type I spin-shift
      upon binding to P450 and thus permitted to determine dissociation constants. For
      the identification of conversion products by NMR spectroscopy, a B. megaterium
      whole-cell system was applied. NMR analysis revealed for the first time the
      ability of CYP109E1 to catalyze an industrially highly important reaction, the
      production of pravastatin from compactin, as well as regioselective oxidations
      generating drug metabolites (6'beta-hydroxy-lovastatin, 3'alpha-hydroxy
      simvastatin, and 4"-hydroxy-simvastatin) and valuable terpene derivatives (3
      hydroxy-alpha-ionone, 4-hydroxy-beta-ionone, 11,12-epoxy-nootkatone, 4(R)-hydroxy
      isolongifolen-9-one, 3-hydroxy-alpha-damascone, 4-hydroxy-beta-damascone, and 3,4
      epoxy-beta-damascone). Besides that, a novel compound, 2-hydroxy-beta
      damascenone, produced by CYP109E1 was identified. Docking calculations using the
      crystal structure of CYP109E1 rationalized the experimentally observed
      regioselective hydroxylation and identified important amino acid residues for
      statin and terpene binding.

PMID- 29018906
TI  - The performance of classification criteria for juvenile spondyloarthropathies.
AB  - Juvenile spondyloarthropathies (JSpA) are a group of rheumatologic diseases with
      a disease onset before 16; characterized with enthesitis, lower extremity
      oligoarthritis, involvement of the axial skeleton and HLA B27 positivity. The
      diversity of classification criteria along with the phenotype heterogeneity makes
      the classification of JSpA challenging. The aim of our study was to evaluate the
      performance of the pre-determined and recently proposed classification criteria
      for JSpA. The study group consisted of 113 patients with JSpA and 150 patients
      with juvenile idiopathic arthritis (JIA). Eligible criteria for JSpA were applied
      to all of the enrolled patients. The analysis of sensitivity, specificity and the
      kappa index were used to verify the performance of the JSpA criteria. The Amor
      criteria showed the highest sensitivity (98.2%) while the ASAS criteria for the
      axial SpA had highest specificity (100%). The sensitivity and specificity of the
      remaining criteria were: 93.8 and 63.8% for ESSG, 95.6 and 62.7% for Garmisch
      Partenkirchen, 91.2 and 75.3% for ASAS criteria for peripheral SpA, respectively.
      Criteria proposed by our group showed the high sensitivity, specificity and kappa
      value: 90.3, 90.7, 0.843%, respectively. We suggest that criteria proposed by us
      could be used in the classification of JSpA. However, neither the pre-determined
      nor the new criteria are totally adequate and efficacious for the classification
      and diagnosis of this disease. The evaluation of the validity and reliability of
      proposed criteria in multicentric studies are mandatory, to increase its utility
      in routine clinical practice.

PMID- 29018907
TI  - MRI sport-specific pulley imaging.
AB  - OBJECTIVE: We aim to create a novel MRI methodology that employs sport-specific
      stress views for imaging finger pulley injuries in the evaluation of post
      operative healing effectiveness. The goal is to measure the bone to tendon
      distance (BTD), which is the current standard for determining pulley injuries.
      MATERIALS AND METHODS: The athlete was imaged in a crimp-grip stressed position
      to emulate sport-specific biomechanics. A Gradient Echo technique was modified to
      maximize the signal to noise ratio and minimize distortion near the bone and
      tendon, simplifying the determination of the BTD. RESULTS: A stress-crimped hand
      position is imaged in less than one half-minute to enable diagnostic
      visualization of a normal proximal phalanx' bone and tendon via measurement of
      their BTD. CONCLUSION: This novel stress methodology allows for sport-specific
      imaging, which is ideal for determining functional compromise of the hand's
      pulley mechanism. Surgical outcomes may be more sensitively compared when using
      stress views, and these comparisons may then direct optimal repair technique.
      Future studies will utilize this technique to attempt early-stage detection of
      pulley injuries prior to complete rupture.

PMID- 29018908
TI  - Characterization of arthralgia induced by PD-1 antibody treatment in patients
      with metastasized cutaneous malignancies.
AB  - BACKGROUND: PD-1 antibodies (PD1ab) are increasingly used in metastatic melanoma
      and other malignancies. Arthralgia is an underestimated side effect of PD-1
      antibody treatment with unknown cause. Our aim was to characterize PD1ab-induced
      arthralgia. PATIENTS AND METHODS: We retrospectively included patients with
      metastatic cutaneous malignancies treated with pembrolizumab or nivolumab +/-
      ipilimumab at the National Center for Tumor Diseases (Heidelberg) between 01/2013
      and 09/2016. Arthralgia was characterized by laboratory diagnostics, imaging, and
      if indicated, rheumatologic consultation. RESULTS: 26 of 195 patients (13.3%)
      developed arthralgia. The median onset of symptoms was 100 days (7-780 days).
      Most frequently, arthralgia involved large joints (shoulders, knees) in a
      predominantly symmetrical pattern. Only two patients were seropositive for
      rheumatoid factor and/or anti-citrullinated protein antibodies. Ten patients
      developed the clinical picture of arthritis, with seven of them showing synovitis
      in MRI or PET/CT. Five patients showed inflammation in joints pre-damaged by
      osteoarthritis. In 11 patients arthralgia could not be specified. The majority of
      patients was satisfactorily treated with non-steroidal anti-inflammatory drugs
      (NSAIDs), 23.1% required additional low-dose corticosteroids and only 7.6% of our
      patients received further immunosuppressive treatment. Patients with arthralgia
      showed a better treatment response and improved PFS and OS. CONCLUSION:
      Arthralgia is frequent during PD1ab treatment. The clinical picture varies
      between synovitis of predominantly large joints, progressive osteoarthritis and
      arthralgia without evident joint damage. Vast majority of cases can be
      satisfactorily managed by NSAID and/or low-dose corticosteroids.

PMID- 29018909
TI  - The Depth from the Skin to the Celiac Artery Measured Using Computed Tomography
      is a Simple Predictive Index for Longer Operation Time During Laparoscopic Distal
      Gastrectomy.
AB  - BACKGROUND: Body mass index (BMI) is commonly used to classify obesity. However,
      BMI does not always reflect the degree of visceral fat. This study aimed to
      clarify the usefulness of measuring the depth from the skin to the celiac artery
      using computed tomography, as a simple predictive index for longer operation time
      during laparoscopic distal gastrectomy (LDG). METHODS: From September 2012 to
      March 2016, 66 patients who underwent LDG with D1+ lymph node dissection were
      included. The depth from the skin to the bifurcation of the celiac artery was
      defined as 'skin-to-celiac artery distance (SCD).' The patients were divided into
      two groups based on the median operation time. [Time scenarios from omentum
      incision to specimen extirpation and infrapyloric and suprapancreatic lymph node
      dissections (I-LND, S-LND) were assessed.] The factors eliciting a longer
      operation time than the median operation time were investigated. RESULTS: From
      omentum incision to specimen extirpation, BMI, thickness of subcutaneous fat
      (TSF), and SCD (P = 0.002, P = 0.039, P < 0.001) were the factors associated with
      longer operation time. Furthermore, BMI, TSF, and SCD in I-LND (P = 0.008, P =
      0.022, P < 0.001) and BMI and SCD in S-LND (P < 0.001, P < 0.001) were associated
      with longer operation time. The multivariate analysis showed that a long SCD was
      the only significant independent factor to predict an operation time longer than
      the median operation time (P = 0.001). The best cutoff level of SCD calculated
      using the receiver operating characteristic curve was 88 mm. CONCLUSIONS: This
      study demonstrated that SCD is a simple predictive index for longer operation
      time during LDG.

PMID- 29018910
TI  - Incidence of delayed union one year after peri-acetabular osteotomy based on
      computed tomography.
AB  - BACKGROUND: Pubic bone nonunion and delayed union are reported as post-operative
      complications after peri-acetabular osteotomy (PAO). However, few studies have
      determined the incidence of delayed union using computed tomography (CT) scans.
      This study aimed to determine the incidence of delayed union at one year after
      PAO using X-ray and CT scans. METHODS: We performed a retrospective review of 150
      hips in 132 consecutive patients with acetabular dysplasia who underwent PAO
      between January 2012 and June 2016 and evaluated 107 hips for which pelvic CT
      scans taken at one year after PAO were available. Clinical evaluations included
      age at surgery, weight, body mass index (BMI) and history. Radiographic
      evaluations were to assess pubic, ischial and iliac delayed union at one year
      post-operatively. RESULTS: Based on X-ray analysis, the incidence of delayed
      union in the pubic, ischial and iliac bones was 11.2% (12 hips), 5.6% (6 hips)
      and 0% (0 hips), respectively, and20.6% (22 hips), 8.4% (9 hips) and 0% (0 hips),
      respectively, based on CT scans. CONCLUSION: The incidence of delayed union of
      the pubis and ischium at one year after PAO according to CT scans was higher than
      that based on X-ray imaging. CT scans are useful in patients with some symptoms
      at the osteotomy site. LEVEL OF EVIDENCE: Level III.

PMID- 29018911
TI  - Postoperative Bleeding After Laparoscopic Pancreaticoduodenectomy: the Achilles'
      Heel?
AB  - BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) is technically demanding,
      and its impact on postoperative outcomes remains controversial. OBJECTIVE: To
      compare short-term outcomes between laparoscopic versus open
      pancreaticoduodenectomy (OPD) in order to assess the safety of LPD. METHODS: From
      2002 to 2014, all consecutive patients undergoing LPD or OPD at two tertiary
      centers were retrospectively analyzed. Patients were matched for demographics,
      comorbidities, pathological diagnosis, and pancreatic texture. Results for the
      two groups were compared for postoperative outcomes. RESULTS: Sixty-five LPD were
      performed and compared to 290 OPD. In the whole population, postoperative
      pancreatic fistula (PF) was higher in the LPD group, but the proportion of
      ampullary adenocarcinoma (25 vs. 10%, p = 0.004) and soft pancreatic parenchyma
      (52 vs. 38%, p = 0.001) were higher in the LDP group. After matching (n = 65),
      LPD was associated with longer operative time (429 vs. 328 min, p < 0.001) and
      lower blood loss (370 vs. 515 mL, p = 0.047). The PF rate and its severity were
      similar (33 vs. 27%, p = 0.439, p = 0.083) in the two groups. However, both
      complications (78 vs. 71%, p = 0.030) and major complications (40 vs. 23%, p =
      0.033) were more frequent in the LPD group. LPD patients experience more
      postoperative bleeding (21 vs. 14%, p = 0.025) compared to their open
      counterparts. In multivariate analysis, perioperative transfusion (OR = 5 IC 95%
      (1.5-16), p = 0.008), soft pancreas (OR = 2.5 IC 95% (1.4-4.6), p = 0.001), and
      ampullary adenocarcinoma (OR = 2.6 IC 95% (1.2-5.6), p = 0.015) were independent
      risks factors of major complications. CONCLUSION: Despite lower blood loss and
      lower intraoperative transfusion, LPD leads to higher rate of postoperative
      complications with postoperative bleeding in particular.

PMID- 29018912
TI  - A Nationwide Population-Based Study on the Survival of Patients with Pancreatic
      Neuroendocrine Tumors in The Netherlands.
AB  - BACKGROUND: Large population-based studies give insight into the prognosis and
      treatment outcomes of patients with pancreatic neuroendocrine tumors (pNETs).
      Therefore, we provide an overview of the treatment and related survival of pNET
      in the Netherlands. METHODS: Patients diagnosed with pNET between 2008 and 2013
      from the Netherlands Cancer Registry were included. Patient, tumors and treatment
      characteristics were reported. Survival analyses with log-rank testing were
      performed to compare survival. RESULTS: In total, 611 patients were included.
      Median follow-up was 25.7 months, and all-cause mortality was 42%. Higher tumor
      grade and TNM stage were significantly associated with worse survival in both the
      overall and metastasized population. The effect of distant metastases on survival
      was more significant in lower tumor stages (T1-3 p < 0.05, T4 p = 0.074).
      Resection of the primary tumor was performed in 255 (42%) patients. Patients who
      underwent surgery had the highest 5-year survival (86%) compared to PRRT (33%),
      chemotherapy (21%), targeted therapy and somatostatin analogs (24%) (all p <
      0.001). Patients with T1M0 tumors (n = 115) showed favorable survival after
      surgical resection (N = 95) compared to no therapy (N = 20, p = 0.008). Resection
      also improved survival significantly in patients with metastases compared to
      other treatments (all p > 0.05). Without surgery, PRRT showed the best survival
      curves in patients with distant metastases. Grade 3 tumors and surgical resection
      were independently associated with survival (HR 7.23 and 0.12, respectively).
      CONCLUSION: Surgical resection shows favorable outcome for all pNET tumors,
      including indolent tumors and tumors with distant metastases. Prospective trials
      should be initiated to confirm these results.

PMID- 29018915
TI  - [Non-cryoconserving storage strategies for fresh osteochondral allografts].
AB  - BACKGROUND: The clinical outcome of fresh allogeneic osteochondral allografts
      (OCA) is greatly dependent on the number of viable chondrocytes at the time of
      implantation. The selection and preparation of a suitable recipient can be very
      time-consuming and the number of tissue donors is greatly limited; therefore, the
      preservation of high allograft viability before transplantation is a focal point
      of current research. OBJECTIVE: The objective of this review is to give an
      overview of established storage strategies for OCA and to serve as a decision
      making aid for German clinics in the choice of a suitable storage strategy.
      MATERIAL AND METHODS: A search of the literature published between January 2002
      and May 2017 was independently performed by two persons with respect to original
      works on storage strategies of OCA with a focus on storage medium, use of fetal
      bovine serum, storage temperature and change of medium. A total of 20 suitable
      studies were selected for this review. RESULTS: Based on the current studies a
      clearly superior storage solution could not be identified; however, storage at 4 
      degrees C seems to give better results with respect to cell viability than
      storage at 37  degrees C. High chondrocyte viability rates after 28 days of
      storage were also achieved using media without the addition of fetal bovine
      serum. CONCLUSION: A major difficulty in comparing the relevant studies on
      storage solutions is that multiple aspects in the study design varied between the
      studies. Due to this no definite conclusion on what the ideal storage strategy
      should look like could be drawn. Further studies are needed to conclusively show
      whether cell culture medium-based storage solutions are truly superior to those
      based on Ringer-lactate solutions.

PMID- 29018914
TI  - The Effect of a Surgery Residency Program and Enhanced Educational Activities on
      Trauma Mortality in Sub-Saharan Africa.
AB  - INTRODUCTION: To address the need for more surgical providers in low-resource
      settings, a collaboration to create a surgical residency-training program for
      local Malawian physicians was established in 2009. This study sought to describe
      the short-term independent effect of a surgical residency program on trauma
      mortality at a tertiary trauma center in sub-Saharan Africa. METHODS: We
      conducted a retrospective analysis of all patients recorded in the trauma
      surveillance registry of Kamuzu Central Hospital in Lilongwe, Malawi, from 2009
      (three residents) through 2014 (11 residents). Log-binominal regression modeling
      was used to compare the risk ratio of death compared to the referent year of
      2009, when the program was started, after adjusting for relevant covariates.
      Primary injury type was used as a surrogate for injury severity. RESULTS: In
      total, 82,534 patients were recorded into the KCH Trauma Registry during the
      study period. Mean age was 23.1 years (SD 15.7) with a male preponderance
      (72.1%). Trauma patient volume increased from 8725 patients in 2009 to 15,998
      patients in 2014. Each year had a significantly decreased risk of death compared
      to 2009 when adjusted for primary injury type, age, and gender, with an adjusted
      risk ratio of 0.73 (95% CI 0.58, 0.90) in 2010 and 0.52 (95% CI 0.43, 0.62) in
      2014. CONCLUSION: The global burden of surgical diseases cannot be attenuated in
      the presence of an inadequate surgical workforce. After institution of a surgery
      residency program, adjusted injury-associated mortality decreased each year
      despite substantial increases in trauma patient volume. In low-resource settings,
      establishment of a surgical residency program significantly improves trauma
      associated outcomes.

PMID- 29018917
TI  - In Vitro Response of Rumen Microbiota to the Antimethanogenic Red Macroalga
      Asparagopsis taxiformis.
AB  - The red macroalga Asparagopsis taxiformis has been shown to significantly
      decrease methane production by rumen microbial communities. This has been
      attributed to the bioaccumulation of halogenated methane analogues produced as
      algal secondary metabolites. The objective of this study was to evaluate the
      impact of A. taxiformis supplementation on the relative abundance of methanogens
      and microbial community structure during in vitro batch fermentation. Addition of
      A. taxiformis (2% organic matter) or the halogenated methane analogue bromoform
      (5 MUM) reduced methane production by over 99% compared to a basal substrate-only
      control. Quantitative PCR confirmed that the decrease in methane production was
      correlated with a decrease in the relative abundance of methanogens. High
      throughput 16S ribosomal RNA gene amplicon sequencing showed that both treatments
      reduced the abundance of the three main orders of methanogens present in
      ruminants (Methanobacteriales, Methanomassiliicoccales and Methanomicrobiales).
      Shifts in bacterial community structure due to the addition of A. taxiformis and
      5 MUM bromoform were similar and concomitant with increases in hydrogen
      concentration in the headspace of the fermenters. With high potency and broad
      spectrum activity against rumen methanogens, A. taxiformis represents a promising
      natural strategy for reducing enteric methane emissions from ruminant livestock.

PMID- 29018913
TI  - Meeting report of the 8th International Conference on cGMP "cGMP: generators,
      effectors, and therapeutic implications" at Bamberg, Germany, from June 23 to 25,
      2017.
AB  - Although the Nobel Prize for the discovery of nitric oxide (NO) dates back almost
      20 years now, the knowledge about cGMP signaling is still constantly increasing.
      It looks even so that our understanding of the role of the soluble guanylyl
      cyclase (sGC) and particulate guanylyl cyclase (pGC) in health and disease is in
      many aspects at the beginning and far from being understood. This holds even true
      for the therapeutic impact of innovative drugs acting on both the NO/sGC and the
      pGC pathways. Since cGMP, as second messenger, is involved in the pathogenesis of
      numerous diseases within the cardiovascular, pulmonary, renal, and endocrine
      systems and also plays a role in neuronal, sensory, and tumor processes, drug
      applications might be quite broad. On the 8th International Conference on cGMP,
      held in Bamberg, Germany, world leading experts came together to discuss these
      topics. All aspects of cGMP research from the basic understanding of cGMP
      signaling to clinical applicability were discussed in depth. In addition, present
      and future therapeutic applications of cGMP-modulating pharmacotherapy were
      presented ( http://www.cyclicgmp.net/index.html ).

PMID- 29018918
TI  - [Report of the Working Group on Osseous, Joint and Soft Tissue Pathology : DGP
      conference on 22nd June 2017, Erlangen].

PMID- 29018916
TI  - Potential applications of biosurfactant rhamnolipids in agriculture and
      biomedicine.
AB  - Rhamnolipids have recently emerged as promising bioactive molecules due to their
      novel structures, diverse and versatile biological functions, lower toxicity,
      higher biodegradability, as well as production from renewable resources. The
      advantages of rhamnolipids make them attractive targets for research in a wide
      variety of applications. Especially rhamnolipids are likely to possess potential
      applications of the future in areas such as biomedicine, therapeutics, and
      agriculture. The purpose of this mini review is to provide a comprehensive
      prospective of biosurfactant rhamnolipids as potential antimicrobials, immune
      modulators, and virulence factors, and anticancer agents in the field of
      biomedicine and agriculture that may meet the ever-increasing future
      pharmacological treatment and food safety needs in human health.

PMID- 29018919
TI  - Nomenclature in Ventral Hernia Repair.

PMID- 29018920
TI  - Pro-inflammatory dietary pattern is associated with fractures in women: an eight
      year longitudinal cohort study.
AB  - : In this study, during 8 years of follow-up, we reported that higher dietary
      inflammatory index values were associated with a higher risk of incident
      fractures in women, but not in men, after adjusting for potential confounders.
      INTRODUCTION: Inflammation is a key risk factor for many adverse outcomes in
      older people. While diet is a potential source of inflammation, little is known
      about the impact of inflammatory diet on fractures. Thus, we investigated whether
      higher Dietary Inflammatory Index (DII)TM (r) scores are associated with
      fractures in a cohort of North American people. METHODS: This longitudinal study
      with a follow-up of 8 years included 3648 participants (1577 males and 2071
      females; mean age = 60.6 years) with/at risk of knee osteoarthritis participating
      with in the Osteoarthritis Initiative. DII scores were calculated using the
      validated Block Brief 2000 Food Frequency Questionnaire, categorized into sex
      specific quintiles. Information on fractures was obtained through self-reported
      history of fractures at hip, spine, and forearm. The relationship between
      baseline DII score and incident fracture was assessed through a Cox's regression
      analysis, adjusted for potential baseline confounders, and reported as hazard
      ratios (HRs). RESULTS: During 8 years of follow-up, 560 individuals developed
      fractures (15.4%). Adjusting for 10 potential confounders, women in the highest
      DII score quintile (i.e., most pro-inflammatory diet) had a significantly higher
      risk for fractures (HR = 1.46; 95% CI = 1.02-2.11) compared to women in the
      lowest quintile. An increase in one standard deviation of DII scores
      significantly predicted fracture onset in women (adjusted HR = 1.14; 95% CI =
      1.02-1.27). The association between DII score and fractures was not significant
      among men or in the sample as whole. CONCLUSION: Pro-inflammatory diet is
      associated with a higher incidence of fractures in women but not men.

PMID- 29018921
TI  - Genetics of trehalose biosynthesis in desert-derived Aureobasidium melanogenum
      and role of trehalose in the adaptation of the yeast to extreme environments.
AB  - Melanin plays an important role in the stress adaptation of Aureobasidium
      melanogenum XJ5-1 isolated from the Taklimakan desert. A trehalose-6-phosphate
      synthase gene (TPS1 gene) was cloned from K5, characterized, and then deleted to
      determine the role of trehalose in the stress adaptation of the albino mutant K5.
      No stress response element and heat shock element were found in the promoter of
      the TPS1 gene. Deletion of the TPS1 gene in the albino mutant rendered a strain
      DT43 unable to synthesize any trehalose, but DT43 still could grow in glucose,
      suggesting that its hexokinase was insensitive to inhibition by trehalose-6
      phosphate. Overexpression of the TPS1 gene enhanced trehalose biosynthesis in
      strain ET6. DT43 could not grow at 33  degrees C, whereas K5, ET6, and XJ5-1
      could grow well at this temperature. Compared with K5 and ET6, DT43 was highly
      sensitive to heat shock treatment, high oxidation, and high desiccation, but all
      the three strains demonstrated the same sensitivity to UV light and high NaCl
      concentration. Therefore, trehalose played an important role in the adaptation of
      K5 to heat shock treatment, high oxidation, and high desiccation.

PMID- 29018922
TI  - Long-Term Follow-Up of Retromuscular Incisional Hernia Repairs: Recurrence and
      Quality of Life.
AB  - PURPOSE: Incisional hernia repair (IHR) with a mesh is necessary to achieve low
      recurrence rates and pain relief. In the short term, quality of life (QoL) is
      restored by IHR. Two centers pioneered the IHR in Sweden with the highly
      standardized Rives-Stoppa technique using a retromuscular mesh. We assessed long
      term follow-up of recurrence rate and QoL. METHODS: Medical records were searched
      for IHRs performed from 1998 to 2006 and included living patients with midline
      repairs. Questionnaires about physical status, complaints, and QoL (SF-36) were
      mailed, offering a clinical examination. Assessment of medical records of later
      surgery was performed in 2015. RESULTS: Three hundred and one patients with
      midline incisional repairs were identified, and 217 accepted participation. Of
      these, 103 attended a clinical examination. Follow-up was 7 years until
      examination and 11 years to reassessment of medical records. In 26%, recurrent
      hernias were repaired. Postoperative complications were 26% Clavien-Dindo grade I
      II and 1% grade III-IV. Mesh infections occurred in 1.4% without mesh removals,
      and 4% were reoperated because of complications. Overall recurrence rate was 8.1%
      and two-third of which were diagnosed at clinical examination. Recurrence after
      primary and recurrent hernia repair was 7.1 and 10.9%, respectively. Of all
      patients, 80% were satisfied; dissatisfaction was primarily caused by recurrence
      and chronic pain. SF-36 scores were 0.2 SD lower than the norm in all subscales,
      similar to those with 1-2 chronic conditions. CONCLUSIONS: Midline retromuscular
      mesh IHR has a low long-term recurrence rate even after recurrent repair. Patient
      satisfaction was high although QoL was reduced.

PMID- 29018923
TI  - Is drug-induced bone loss acceptable in premenopausal women? A practical fracture
      risk modeling exercise.
AB  - : Premenopausal bone loss increases fracture risk later in life. Depending on
      peak values, varying degrees of bone mass and microarchitectural loss can be
      tolerated. We suggest that risk-benefit assessments of drugs that cause
      premenopausal bone loss be individualized considering baseline status and
      subsequent BMD and TBS loss. INTRODUCTION: It is logical that drug-induced loss
      of bone mass and microarchitecture in young adults increase fracture risk later
      in life. However, no existing data quantify how drug-induced bone loss in younger
      adults impacts fracture risk later in life. As such, no guidance exists to
      address the question "How much, if any, drug-induced bone loss in premenopausal
      women is acceptable?" Thus, we performed a systematic fracture risk modeling
      exercise examining various degrees of bone loss, and estimated the impact on 10
      year major osteoporosis-related fracture risk later in life. METHODS: The FRAX(r)
      tool was used in conjunction with BMD and trabecular bone score (TBS) adjustment
      to estimate major osteoporotic fracture probability later in life resulting from
      varying degrees of hypothetical premenopausal drug-induced BMD and TBS loss. The
      resulting 10-year fracture probabilities were assessed against the US and the UK
      treatment guidance to determine the amount of premenopausal BMD and TBS loss that
      would result in a recommendation to initiate medical treatment to reduce fracture
      risk later in life that would not otherwise have been recommended in the absence
      of premenopausal bone loss. RESULTS: For women whose peak bone mass is between
      the 5th and 50th percentiles, varying degrees of BMD and TBS loss could be
      tolerated without reaching treatment thresholds. The degree of tolerable bone
      loss was primarily dependent on baseline bone status. Those whose peak BMD and
      TBS are in the 50th percentile or above could tolerate a 10% reduction in BMD and
      TBS without reaching treatment thresholds by age 75, whereas those in the 5th
      percentile would reach treatment thresholds by age 75 with no drug-induced
      reduction in BMD or TBS. Women in the 25th percentile could tolerate a 4% BMD
      loss and 2% TBS decline without reaching treatment thresholds by age 75.
      CONCLUSIONS: For clinicians and regulatory bodies to assess the consequence of
      drug-induced premenopausal bone loss, we propose an individualized approach
      considering both loss of BMD and TBS in concert with baseline bone status and the
      resultant effect on fracture risk in later life using the assumption that such
      losses are irreversible.

PMID- 29018924
TI  - Rapid volumetric photoacoustic tomographic imaging with a Fabry-Perot ultrasound
      sensor depicts peripheral arteries and microvascular vasomotor responses to
      thermal stimuli.
AB  - PURPOSE: To determine if a new photoacoustic imaging (PAI) system successfully
      depicts (1) peripheral arteries and (2) microvascular circulatory changes in
      response to thermal stimuli. METHODS: Following ethical permission, 8 consenting
      subjects underwent PAI of the dorsalis pedis (DP) artery, and 13 completed PAI of
      the index fingertip. Finger images were obtained after immersion in warm (30-35 
      degrees C) or cold (10-15  degrees C) water to promote vasodilation or
      vasoconstriction. The PAI instrument used a Fabry-Perot interferometeric
      ultrasound sensor and a 30-Hz 750-nm pulsed excitation laser. Volumetric images
      were acquired through a 14 * 14 * 14-mm volume over 90 s. Images were evaluated
      subjectively and quantitatively to determine if PAI could depict cold-induced
      vasoconstriction. The full width at half maximum (FWHM) of resolvable vessels was
      measured. RESULTS: Fingertip vessels were visible in all participants, with mean
      FWHM of 125 MUm. Two radiologists used PAI to correctly identify vasoconstricted
      fingertip capillary beds with 100% accuracy (95% CI 77.2-100.0%, p < 0.001). The
      number of voxels exhibiting vascular signal was significantly smaller after cold
      water immersion (cold: 5263 voxels; warm: 363,470 voxels, p < 0.001). The DP
      artery was visible in 7/8 participants (87.5%). CONCLUSION: PAI achieves rapid,
      volumetric, high-resolution imaging of peripheral limb vessels and the
      microvasculature and is responsive to vasomotor changes induced by thermal
      stimuli. KEY POINTS: * Fabry-Perot interferometer-based photoacoustic imaging
      (PAI) generates volumetric, high-resolution images of the peripheral vasculature.
      * The system reliably detects thermally induced peripheral vasoconstriction (100%
      correct identification rate, p < 0.001). * Vessels measuring less than 100 MUm in
      diameter can be depicted in vivo.

PMID- 29018925
TI  - The diagnostic performance of shear-wave elastography for liver fibrosis in
      children and adolescents: A systematic review and diagnostic meta-analysis.
AB  - OBJECTIVE: To assess the diagnostic performance of shear-wave elastography for
      determining the severity of liver fibrosis in children and adolescents. METHODS:
      An electronic literature search of PubMed and EMBASE was conducted. Bivariate
      modelling and hierarchical summary receiver-operating-characteristic modelling
      were performed to evaluate the diagnostic performance of shear-wave elastography.
      Meta-regression and subgroup analyses according to the modality of shear-wave
      imaging and the degree of liver fibrosis were also performed. RESULTS: Twelve
      eligible studies with 550 patients were included. Shear-wave elastography showed
      a summary sensitivity of 81 % (95 % CI: 71-88) and a specificity of 91 % (95 %
      CI: 83-96) for the prediction of significant liver fibrosis. The number of
      measurements of shear-wave elastography performed was a significant factor
      influencing study heterogeneity. Subgroup analysis revealed shear-wave
      elastography to have an excellent diagnostic performance according to each degree
      of liver fibrosis. Supersonic shear imaging (SSI) had a higher sensitivity
      (p<.01) and specificity (p<.01) than acoustic radiation force impulse imaging
      (ARFI). CONCLUSIONS: Shear-wave elastography is an excellent modality for the
      evaluation of the severity of liver fibrosis in children and adolescents.
      Compared with ARFI, SSI showed better diagnostic performance for prediction of
      significant liver fibrosis. KEY POINTS: * Shear-wave elastography is beneficial
      for determining liver fibrosis severity in children. * Shear-wave elastography
      showed summary sensitivity of 81 %, specificity of 91 %. * SSI showed better
      diagnostic performance than ARFI for significant liver fibrosis.

PMID- 29018926
TI  - Optimisation of window settings for traditional and noise-optimised virtual
      monoenergetic imaging in dual-energy computed tomography pulmonary angiography.
AB  - OBJECTIVES: To define optimal window settings for displaying virtual
      monoenergetic images (VMI) of dual-energy CT pulmonary angiography (DE-CTPA).
      METHODS: Forty-five patients who underwent clinically-indicated third-generation
      dual-source DE-CTPA were retrospectively evaluated. Standard linearly-blended
      (M_0.6), 70-keV traditional VMI (M70), and 40-keV noise-optimised VMI (M40+)
      reconstructions were analysed. For M70 and M40+ datasets, the subjectively best
      window setting (width and level, B-W/L) was independently determined by two
      observers and subsequently related with pulmonary artery attenuation to calculate
      separate optimised values (O-W/L) using linear regression. Subjective evaluation
      of image quality (IQ) between W/L settings were assessed by two additional
      readers. Repeated measures of variance were performed to compare W/L settings and
      IQ indices between M_0.6, M70, and M40+. RESULTS: B-W/L and O-W/L for M70 were
      460/140 and 450/140, and were 1100/380 and 1070/380 for M40+, respectively,
      differing from standard DE-CTPA W/L settings (450/100). Highest subjective scores
      were observed for M40+ regarding vascular contrast, embolism demarcation, and
      overall IQ (all p<0.001). CONCLUSIONS: Application of O-W/L settings is
      beneficial to optimise subjective IQ of VMI reconstructions of DE-CTPA. A width
      slightly less than two times the pulmonary trunk attenuation and a level
      approximately of overall pulmonary vessel attenuation are recommended. KEY
      POINTS: * Application of standard window settings for VMI results in inferior
      image perception. * No significant differences between B-W/L and O-W/L for
      M70/M40+ were observed. * O-W/L for M70 were 450/140 and were 1070/380 for M40+.
      * Improved subjective IQ characteristics were observed for VMI displayed with O
      W/L.

PMID- 29018929
TI  - Dumbbell-shaped atypical teratoid rhabdoid tumor in the cervical spine mimicking
      schwannoma.

PMID- 29018927
TI  - Whole body magnetic resonance in indolent lymphomas under watchful waiting: The
      time is now.
AB  - : ?: The indolent non-Hodgkin lymphomas (i-NHLs) are characterised by 'indolent'
      clinical behaviour with slow growth and prolonged natural history. The watchful
      waiting (WW) strategy is a frequently employed treatment option in these
      patients. This implies a strict monitoring by imaging examinations, including 18F
      fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG
      PET/CT) and CT. A major concern is radiation exposure due to regularly monitoring
      by conventional imaging procedures. Several studies have demonstrated the
      reliability of whole-body magnetic resonance imaging (WB-MRI) for lymphoma
      staging. WB-MRI could be useful for active surveillance in i-NHLs providing the
      suspect of disease progression that can be then confirmed by additional
      diagnostic procedures, including 18F-FDG-PET/CT. The directive 2013/59 by the
      European Union claims that if a radiation-free imaging technique allows obtaining
      the same diagnostic results, it should be invariably used. In this setting, WB
      MRI may be considered a reasonable option in i-NHLs under WW, replacing imaging
      modalities that cause exposure to ionising radiations. This will help to reduce
      the cancer risk in i-NHL patients for whom chemo-/radiotherapy remain the usual
      treatment options following the usually long WW phase. The scientific community
      should raise the awareness of the risk of ionising radiations in i-NHLs and the
      emphasise the need for establishing the proper place of WB-MRI in lymphoma
      imaging. KEY POINTS: * Watchful waiting is a reasonable option in patients with
      indolent non-Hodgkin lymphomas. * Imaging is crucial to monitor patients with
      indolent non-Hodgkin lymphomas. * CT and 18 F-FDG-PET/CT are commonly used,
      implying a substantial radiation exposure. * WB-MRI is highly reliable in
      lymphoma staging. * WB-MRI may be considered to monitor indolent non-Hodgkin
      lymphomas under watchful waiting.

PMID- 29018931
TI  - Analytical evaluation of sensor measurements.

PMID- 29018928
TI  - Tactile localization biases are modulated by gaze direction.
AB  - Identifying the spatial location of touch on the skin surface is a fundamental
      function of our somatosensory system. Despite the fact that stimulation of even
      single mechanoreceptive afferent fibres is sufficient to produce clearly
      localised percepts, tactile localisation can be modulated also by higher level
      processes such as body posture. This suggests that tactile events are coded using
      multiple representations using different coordinate systems. Recent reports
      provide evidence for systematic biases on tactile localisation task, which are
      thought to result from a supramodal representation of the skin surface. While the
      influence of non-informative vision of the body and gaze direction on tactile
      discrimination tasks has been extensively studied, their effects on tactile
      localisation tasks remain largely unexplored. To address this question,
      participants performed a tactile localization task on their left hand under
      different visual conditions by means of a mirror box; in the mirror condition, a
      single stimulus was delivered on participants' hand, while the reflexion of the
      right hand was seen through the mirror; in the object condition, participants
      looked at a box through the mirror, and in the right hand condition, participants
      looked directly at their right hand. Participants reported the location of the
      tactile stimuli using a silhouette of a hand. Results showed a shift in the
      localization of the touches towards the tip of the fingers (distal bias) and the
      thumb (radial biases) across conditions. Critically, distal biases were reduced
      when participants looked towards the mirror compared to when they looked at their
      right hand suggesting that gaze direction reduces the typical proximo-distal
      biases in tactile localization. Moreover, vision of the hand modulates the
      internal configuration of points' locations, by elongating it, in the radio-ulnar
      axis.

PMID- 29018930
TI  - A highly selective electrochemical sensor based on molecularly imprinted
      polypyrrole-modified gold electrode for the determination of glyphosate in
      cucumber and tap water.
AB  - An electrochemical sensor based on molecularly imprinted polypyrrole (MIPPy) was
      developed for selective and sensitive detection of the herbicide glyphosate (Gly)
      in cucumber and tap water samples. The sensor was prepared via synthesis of
      molecularly imprinted polymers on a gold electrode in the presence of Gly as the
      template molecule and pyrrole as the functional monomer by cyclic voltammetry
      (CV). The sensor preparation conditions including the ratio of template to
      functional monomers, number of CV cycles in the electropolymerization process,
      the method of template removal, incubation time, and pH were optimized. Under the
      optimal experimental conditions, the DPV peak currents of
      hexacyanoferrate/hexacyanoferrite changed linearly with Gly concentration in the
      range from 5 to 800 ng mL-1, with a detection limit of 0.27 ng mL-1 (S/N = 3).
      The sensor was used to detect the concentration of Gly in cucumber and tap water
      samples, with recoveries ranging from 72.70 to 98.96%. The proposed sensor showed
      excellent selectivity, good stability and reversibility, and could detect the Gly
      in real samples rapidly and sensitively. Graphical abstract Schematic
      illustration of the experimental procedure to detect Gly using the MIPPy
      electrode.

PMID- 29018932
TI  - Analysis of Growth, Nutritional Status and Hospital Visitation Scores Associated
      with Reflux After Nissen Fundoplication in Neurologically Impaired Children with
      Gastroesophageal Reflux.
AB  - BACKGROUND: Neurologically impaired children (NIC) often experience swallowing
      difficulties and gastroesophageal reflux disease (GERD). Although these
      conditions could place children in a state of poor nutritional status and prevent
      them from thriving, there is insufficient research evaluating growth and
      nutritional status following fundoplication in these patients. METHOD: This is a
      retrospective study of patients who were neurologically impaired and underwent
      Nissen fundoplication between April 2001 and March 2015. Seventy-six patients
      were enrolled, and the follow-up period was 12 months or longer. Growth was
      measured by the change in body weight and height. Nutritional status was measured
      by the change in body mass index, serum albumin and protein level. RESULTS:
      Median age at operation was 1.85 years old, and median body weight was 10 kg. The
      respective Z scores for weight and height showed significant improvements after 1
      year since the operation compared to 1 year within the operation (-2.42 +/- 2.19
      vs. -1.31 +/- 1.96, P < 0.001) (-1.6 +/- 2.16 vs. -1.05 +/- 1.69, P = 0.002). The
      respective Z scores for body mass index, albumin and protein also showed
      improvements after 1 year since the operation compared to 1 year within the
      operation (-2.07 +/- 2.99 vs. -0.89 +/- 2.1, P < 0.001) (3.55 +/- 0.48 vs. 3.86
      +/- 0.45, P < 0.001) (6.22 +/- 0.76 vs. 6.65 +/- 0.51, P < 0.001). Hospital
      visitation scores associated with reflux were significantly lower after the
      operation (4.1 +/- 3.43 vs. 1.18 +/- 1.67, P < 0.001). CONCLUSIONS: In summary,
      after Nissen fundoplication in NIC with GER, growth and nutritional status
      improved significantly. Also, hospital visitation scores associated with reflux
      decreased after the operation.

PMID- 29018933
TI  - From Osteoimmunology to Osteomicrobiology: How the Microbiota and the Immune
      System Regulate Bone.
AB  - Osteomicrobiology refers to the role of microbiota in bone health and the
      mechanisms by which the microbiota regulates post-natal skeletal development,
      bone aging, and pathologic bone loss. Here, we review recent reports linking gut
      microbiota to changes in bone phenotype. A pro-inflammatory cytokine milieu
      drives bone resorption in conditions such as sex steroid hormone deficiency. The
      response of the immune system to activation by the microbiome results in
      increased circulating osteoclastogenic cytokines in a T cell-dependent mechanism.
      Additionally, gut microbiota affect bone homeostasis through nutrient absorption,
      mediation of the IGF-1 pathway, and short chain fatty acid and metabolic
      products. Manipulation of microbiota through prebiotics or probiotics reduces
      inflammatory cytokine production, leading to changes in bone density. One
      mechanism of probiotic action is through upregulating tight junction proteins,
      increasing the strength of the gut epithelial layer, and leading to less antigen
      presentation and less activation of intestinal immune cells. Thus, prebiotics or
      probiotics may represent a future therapeutic avenue for ameliorating the risk of
      postmenopausal bone loss in humans.

PMID- 29018934
TI  - Quantitative susceptibility mapping of the motor cortex: a comparison of
      susceptibility among patients with amyotrophic lateral sclerosis, cerebrovascular
      disease, and healthy controls.
AB  - PURPOSE: The purpose of this study was to investigate the differences in motor
      cortex susceptibility among patients with amyotrophic lateral sclerosis (ALS),
      cerebrovascular disease (CVD), and healthy controls using quantitative
      susceptibility mapping (QSM). METHODS: We retrospectively reviewed 78 QSM images
      from 26 patients with ALS, 26 age- and sex-matched patients with CVD, and 26
      healthy controls. A region of interest was drawn in the hand lobule of both the
      motor cortexes and subcortical white matter. The relative susceptibility (RS) of
      the motor cortex was obtained by subtracting the susceptibility of the
      subcortical white matter from that of the motor cortex. We compared the
      cortexmean, cortexmax, subcortical white mattermean, RSmean, and RSmax values
      among the three groups using analysis of variance and Tukey's post hoc test.
      Receiver operating characteristic (ROC) curve analysis was also performed.
      RESULTS: There were significant differences in the cortexmean, cortexmax, RSmean,
      and RSmax among the three groups, with higher values in patients with ALS (p =
      0.01, p = 0.004, p < 0.001, and p < 0.001, respectively). Subcortical white
      mattermean was significantly lower in patients with ALS compared with patients
      with CVD and healthy controls (p = 0.04). ROC curve analysis showed that the area
      under the curve of RSmean was 0.70, the highest among the measured parameters.
      CONCLUSION: Quantitative measurements of susceptibility of the motor cortex with
      QSM demonstrate its potential as an imaging biomarker in ALS patients.

PMID- 29018936
TI  - [Chameleon spondylodiscitis : Challenge for geriatricians].
AB  - The incidence of spondylodiscitis is increasing and attributable to an aging
      population with multimorbidities. Spondylodiscitis represents a life-threatening
      disease. Typical clinical manifestations often involve nonspecific symptoms with
      back pain; however, due to the frequent absence of fever the disease is often
      overlooked. Pathogen detection and spinal imaging with magnetic resonance imaging
      (MRI) are essential for the diagnosis. Identification of the causative pathogen
      is particularly important for initiating targeted antibiotic treatment.
      Debridement and stabilization are the mainstays of surgical management, even
      though foreign material must be implanted into the focus of inflammation.

PMID- 29018935
TI  - A curious new role for MRN in Schizosaccharomyces pombe non-homologous end
      joining.
AB  - Chromosomal breaks can be healed by several repair processes, including one
      called non-homologous end-joining (NHEJ) where the two broken ends are ligated
      together with a loss of 0-5 bp of DNA. The protein requirements for NHEJ of cut
      DNA ends in the budding yeast Saccharomyces cerevisiae include its version of the
      Mre11-Rad50-Nbs1 (MRN) complex. In contrast, the fission yeast
      Schizosaccharomyces pombe and mammalian cells do not require MRN for this
      process. Recent work in S. pombe used transposon excision to generate breaks that
      were capped by DNA hairpins, which must be opened to produce ligatable ends.
      Repair in S. pombe was through an NHEJ reaction that now requires MRN.
      Surprisingly, wild type cells and MRN mutants that lack nuclease activity showed
      the same levels of excision. These genetic results suggest that MRN recruits an
      unknown hairpin-opening nuclease for this unusual NHEJ reaction.

PMID- 29018937
TI  - Local effect of zoledronic acid on new bone formation in posterolateral spinal
      fusion with demineralized bone matrix in a murine model.
AB  - BACKGROUND: Posterolateral spinal fusion is a common orthopaedic surgery
      performed to treat degenerative and traumatic deformities of the spinal column.
      In posteriolateral spinal fusion, different osteoinductive demineralized bone
      matrix products have been previously investigated. We evaluated the effect of
      locally applied zoledronic acid in combination with commercially available
      demineralized bone matrix putty on new bone formation in posterolateral spinal
      fusion in a murine in vivo model. METHODS: A posterolateral sacral spine fusion
      in murine model was used to evaluate the new bone formation. We used the sacral
      spine fusion model to model the clinical situation in which a bone graft or
      demineralized bone matrix is applied after dorsal instrumentation of the spine.
      In our study, group 1 received decortications only (n = 10), group 2 received
      decortication, and absorbable collagen sponge carrier, group 3 received
      decortication and absorbable collagen sponge carrier with zoledronic acid in dose
      10 ug, group 4 received demineralized bone matrix putty (DBM putty) plus
      decortication (n = 10), and group 5 received DBM putty, decortication and locally
      applied zoledronic acid in dose 10 ug. Imaging was performed using MicroCT for
      new bone formation assessment. Also, murine spines were harvested for
      histopathological analysis 10 weeks after surgery. RESULTS: The surgery performed
      through midline posterior approach was reproducible. In group with decortication
      alone there was no new bone formation. Application of demineralized bone matrix
      putty alone produced new bone formation which bridged the S1-S4 laminae. Local
      application of zoledronic acid to demineralized bone matrix putty resulted in
      significant increase of new bone formation as compared to demineralized bone
      matrix putty group alone. CONCLUSIONS: A single local application of zoledronic
      acid with DBM putty during posterolateral fusion in sacral murine spine model
      increased significantly new bone formation in situ in our model. Therefore, our
      results justify further investigations to potentially use local application of
      zoledronic acid in future clinical studies.

PMID- 29018939
TI  - [Presacral lesion at the rima ani].
AB  - A 26-year-old woman presented with a painful bulge at the rima ani. The tumor was
      located in the presacral region. Histological examination revealed a well
      circumscribed biphenotypical tumor with papillary configured myxoid areas and
      strongly sclerosing regions. This case of a myxopapillary ependymoma is a rare
      example of a myxoid neoplastic lesion in the sacral region.

PMID- 29018940
TI  - Laparoscopy or laparotomy for adhesive bowel obstruction in children: a
      systematic review and meta-analysis.
AB  - PURPOSE: Adhesive small bowel obstruction (ASBO) is one of the most important
      cause of postoperative morbidity in children who underwent abdominal surgery.
      Laparoscopic management for ASBO in pediatric patients has been reported.
      However, its safety and efficacy has not been evaluated in details. The aim of
      this study is to compare the outcomes of laparoscopy and laparotomy for the
      treatment of ASBO in children. METHODS: A systematic review and meta-analysis
      were performed following the Cochrane Handbook for systematic reviews of
      intervention and the preferred reporting item for systematic reviews and meta
      analysis (PRISMA) and a protocol registered in PROSPERO (CRD42017067914). The
      primary outcome was the number of intraoperative and postoperative complications.
      The secondary outcome was length of hospital stay. The risk of bias in non
      randomized studies of interventions (ROBINS-I) tool was used to assess the risk
      of bias. Quality of evidence was summarized using the grades of recommendation,
      assessment, development and evaluation (GRADE) approach. RESULTS: We identified
      three observational studies and no randomized controlled trials. The meta
      analysis was done only for the primary outcome. Complications were significantly
      fewer after laparoscopy compared to laparotomy (Odds ratio = 0.51; 95% CI 0.40
      0.66; p < 0.01; I 2: 0%). The overall risk of bias was considered serious.
      CONCLUSIONS: Our results, based on observational studies, indicate that
      laparoscopy for ASBO was associated with less postoperative complications
      compared to conventional laparotomy. However, the quality of evidence is very
      low. A well-controlled study is needed to assess the efficacy of laparoscopy for
      pediatric patients with ASBO.

PMID- 29018942
TI  - Evaluation of an abbreviated screening MRI protocol for patients at risk for
      hepatocellular carcinoma.
AB  - PURPOSE: In this study, we compare an abbreviated screening MRI protocol (aMRI),
      utilizing only dynamic contrast-enhanced images, to a conventional liver MRI
      (cMRI) for the characterization of observations in at-risk patients. MATERIALS
      AND METHODS: 164 consecutive HCC screening MRIs were retrospectively analyzed.
      Two sets of de-identified image sets were created: one with all acquired
      sequences including T2- and diffusion-weighted sequences (cMRI), and one with
      only T1-weighted precontrast and dynamic post-contrast images utilizing an
      extracellular gadolinium contrast agent (aMRI). Three readers assigned a LI-RADS
      score based on the lesion with the highest LI-RADS category using the aMRI and
      cMRI datasets during separate reads. RESULTS: There was no change between the
      aMRI and cMRI LI-RADS categorization in 93%, 96%, and 96% of cases for readers 1,
      2, and 3, respectively. In the majority of the discrepant cases, the score
      increased from LI-RADS 3 to LI-RADS 4 due to the presence of ancillary features
      on T2 and DWI. Kappa values for interobserver variability demonstrated fair-to
      moderate LI-RADS agreement among the 3 readers. CONCLUSION: There was strong
      agreement between the abbreviated T1-only MRI protocol and a full liver MRI, with
      only 5% of cases changing LI-RADS categorization due to the inclusion of T2 and
      DWI. The estimated time to run this abbreviated MRI is approximately 7-10 min,
      possibly allowing for a more cost-effective screening MRI than our cMRIs.

PMID- 29018941
TI  - Pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia:
      Correlations between computed tomography findings and cerebral complications.
AB  - OBJECTIVES: Computed tomography (CT) is the modality of choice to characterise
      pulmonary arteriovenous malformations (PAVMs) in patients with hereditary
      haemorrhagic telangiectasia (HHT). Our objective was to determine if CT findings
      were associated with frequency of brain abscess and ischaemic stroke. METHODS:
      This retrospective study included patients with HHT-related PAVMs. CT results,
      i.e. PAVM presentation (unique, multiple, disseminated or diffuse), the number of
      PAVMs and the largest feeding artery size, were correlated to prevalence of
      ischaemic stroke and brain abscess. All CTs were reviewed in consensus by two
      radiologists. RESULTS: Of 170 patients, 73 patients had unique (42.9 %), 49
      multiple (28.8 %), 36 disseminated (21.2 %) and 12 diffuse (7.1 %) PAVMs. Fifteen
      patients presented with brain abscess; 26 patients presented with ischaemic
      stroke. The number of PAVMs was significantly correlated with brain abscess (11.5
      vs. 6.2, respectively; p=0.025). The mean diameter of the largest feeding artery
      was significantly correlated with ischaemic stroke frequency (4.9 vs. 3.2 mm,
      respectively; p=0.0098). CONCLUSIONS: The number of PAVMs correlated
      significantly with risk of brain abscess, and a larger feeding artery
      significantly with more ischaemic strokes. These findings can lead to a better
      recognition and management of the PAVMs at risk of cerebral complications. KEY
      POINTS: * Chest CT helps clinicians to facilitate appropriate PAVM management
      strategies. * Pulmonary arteriovenous malformation CT findings are correlated
      with risk of cerebral complications. * Risk of brain abscess is significantly
      correlated with number of PAVMs. * Risk of ischaemic stroke is significantly
      correlated with large feeding artery PAVMs. * Prevalence of observed of brain
      abscess and ischaemic stroke is 26 %.

PMID- 29018943
TI  - Microbial depassivation of Fe(0) for contaminant removal under semi-aerobic
      conditions.
AB  - Increasing evidence has shown that the reaction of zero-valent iron [Fe(0)] by
      oxygen can produce strong oxidants and rapidly oxidize the tractable
      contaminants. However, Fe(0) is vulnerable to passivation in the presence of
      oxygen, which significantly decreases its surface reactivity towards the removal
      of refractory contaminants. Microorganisms capable of reducing ferric iron in the
      presence of oxygen are expected to overcome the limitation of Fe(0) passivation.
      However, no studies to date have shown that microorganisms are able to
      depassivate Fe(0) for the removal of recalcitrant compounds in the presence of
      oxygen. In this study, we demonstrated that the carotenoid-producing Sphingobium
      hydrophobicum C1 was able to significantly enhance the removal of deca-brominated
      diphenyl ether by depassivating Fe(0) and subsequently removing the newly formed
      metabolites under semi-aerobic conditions (> 4 mg/L oxygen). S. hydrophobicum C1
      effectively depassivated Fe(0) and regenerated its reactivity by reducing ferric
      iron under semi-aerobic conditions. Some unique characteristics of S.
      hydrophobicum C1, including the presence of membrane-integrated carotenoids and
      certain cell proteins, were essential for the ferric iron reduction of S.
      hydrophobicum C1 in the presence of oxygen. Our results may provide new insights
      into the bioremediation of persistent pollutants and will contribute to future
      studies to enhance our understanding of microbial iron reduction.

PMID- 29018938
TI  - Heart failure with preserved ejection fraction: current management and future
      strategies : Expert opinion on the behalf of the Nucleus of the "Heart Failure
      Working Group" of the German Society of Cardiology (DKG).
AB  - About 50% of all patients suffering from heart failure (HF) exhibit a reduced
      ejection fraction (EF <= 40%), termed HFrEF. The others may be classified into HF
      with midrange EF (HFmrEF 40-50%) or preserved ejection fraction (HFpEF, EF >=
      50%). Presentation and pathophysiology of HFpEF is heterogeneous and its
      management remains a challenge since evidence of therapeutic benefits on outcome
      is scarce. Up to now, there are no therapies improving survival in patients with
      HFpEF. Thus, the treatment targets symptom relief, quality of life and reduction
      of cardiac decompensations by controlling fluid retention and managing risk
      factors and comorbidities. As such, renin-angiotensin-aldosterone inhibitors,
      diuretics, calcium channel blockers (CBB) and beta-blockers, diet and exercise
      recommendations are still important in HFpEF, although these interventions are
      not proven to reduce mortality in large randomized controlled trials. Recently,
      numerous new treatment targets have been identified, which are further
      investigated in studies using, e.g. soluble guanylate cyclase stimulators,
      inorganic nitrates, the angiotensin receptor neprilysin inhibitor LCZ 696, and
      SGLT2 inhibitors. In addition, several devices such as the CardioMEMS,
      interatrial septal devices (IASD), cardiac contractility modulation (CCM), renal
      denervation, and baroreflex activation therapy (BAT) were investigated in
      different forms of HFpEF populations and some of them have the potency to offer
      new hopes for patients suffering from HFpEF. On the basic research field side,
      lot of new disease-modifying strategies are under development including anti
      inflammatory drugs, mitochondrial-targeted antioxidants, new anti-fibrotic and
      microRNA-guided interventions are under investigation and showed already
      promising results. This review addresses available data of current best clinical
      practice and management approaches based on expert experiences and summarizes
      novel approaches towards HFpEF.

PMID- 29018944
TI  - [Nonautonomous effects of oncogenic YAP in hepatocarcinogenesis].
AB  - BACKGROUND: The transcriptional coactivator yes-associated protein (YAP) is a
      strong oncogene in liver cancer development. OBJECTIVES: To investigate if and
      how YAP-induced paracrine-acting factors are regulated in hepatocytes and liver
      cancer cells. MATERIAL AND METHODS: Transcriptome analysis and proteomics of
      murine wildtype and YAP-transgenic hepatocytes were performed to identify
      paracrine-acting proteins. Molecular and biochemical techniques were used to
      examine the mechanisms of YAP-dependent gene regulation. Gene expression data
      from HCC (hepatocellular carcinoma) patients was evaluated. RESULTS: Several YAP
      dependent, secreted factors (e. g. CXCL10, GDF15, PDGFB) were identified. YAP
      regulates these factors through transcription factors of the TEAD (TEA domain)
      protein family. Moreover, the dysregulation of the YAP-target genes is often
      associated with poor HCC patient prognosis. CONCLUSIONS: YAP induces the
      expression of paracrine-acting factors that may affect the tumor microenvironment
      and therefore support carcinogenesis. This multicellular network could allow the
      development of novel and specific perturbation approaches.

PMID- 29018945
TI  - [Nuclear Her2 expression in hepatocytes in liver disease].
AB  - BACKGROUND: Her2 is a well-known member of the epidermal growth factor receptor
      (EGFR) superfamily, a group of transmembrane receptors that mediate effects of
      proliferation and survival and thus play an important role in tumorigenesis.
      EGFRs can translocate to the nucleus and may mediate DNA repair and cell cycle
      arrest. OBJECTIVES: The aim of this study was to characterize hepatocellular Her2
      expression in different liver diseases. MATERIALS AND METHODS: Her2 expression
      was analyzed by immunohistochemistry in 674 liver biopsies. RESULTS: Hepatocytes
      often revealed a nuclear and cytoplasmic Her2 expression in different liver
      diseases with the strongest association to alcoholic steatohepatitis. The
      histologic parameters of hepatocellular ballooning and the presence of Mallory
      Denk bodies strongly correlated with Her2 positivity. Interestingly, in
      hepatocellular carcinomas (HCC) nuclear Her2 expression was frequently observed.
      Furthermore, Her2 positive hepatocytes showed a loss of estrogen receptor
      expression and increased expression of p21, a cell cycle regulator, and pSTAT3, a
      downstream effector of nuclear Her2. CONCLUSIONS: Nuclear Her2 expression in
      hepatocytes with further metabolic and cell cycle alterations may imply a so far
      unknown mechanism of a stress response. So far, the effects on disease course and
      a possible role of nuclear Her2 in progression to HCC are unclear and the subject
      of future research.

PMID- 29018946
TI  - Bidirectional terminators: an underestimated aspect of gene regulation.
AB  - Recent experimental and computational work revealed that transcriptional
      terminators in Saccharomyces cerevisiae can terminate transcription coming from
      both directions. This mechanism helps budding yeast cope with the pervasive
      nature of transcription by limiting aberrant transcription from invading
      neighboring genes.

PMID- 29018947
TI  - Endoscopic management of petrous apex cholesteatoma.
AB  - We describe a technique for approaching petrous apex cholesteatoma using combined
      lateral microscopic/endoscopic approaches, and discuss the utility of endoscopy
      in managing matrix inside the petrous apex. In our two cases, total view inside
      the petrous apex was achieved under endoscopy without mobilizing the internal
      carotid artery, and the matrix was successfully removed. Neither patient has
      presented with postoperative recurrence thanks to the wide-angle endoscopic view
      inside the petrous apex. Since the number of patients was small, comparisons with
      microscopic treatments are not yet valid, but endoscopes could offer a helpful
      tool for operating inside the petrous apex.

PMID- 29018948
TI  - Knockdown of E-cadherin expression of endometrial epithelial cells may activate
      Wnt/beta-catenin pathway in vitro.
AB  - PURPOSE: E-cadherin, a transmembrane glycoprotein mediating Ca2+-independent
      homotypic cell-cell adhesion in epithelial cell, plays an essential role in
      metastasis. It has been postulated that E-cadherin downregulation is a crucial
      mechanism in the pathogenesis of endometriosis. To evaluate the effect on the
      cell behavior after knockdown of E-cadherin gene (CDH1) in cultured human
      endometrial epithelial cells (EECs) isolated from normal endometrium. METHODS:
      EECs were isolated from the endometrial tissues of fertile woman who underwent
      total hysterectomy due to cervical intraepithelial neoplasia III. CDH1 expression
      was knocked down by small hairpin RNA. The EECs transfected with empty vector
      served as control. Transwell assay was used to test EECs migration or invasion.
      qRT-PCR and western blot were used to detect mRNA and protein levels. RESULTS:
      The results showed that knockdown of E-cadherin expression can increase cell
      migration and invasion, and up-regulate mRNA and protein levels of beta-catenin,
      cyclinD1, and c-myc. CONCLUSIONS: Down-regulation of E-cadherin expression may
      activate the Wnt/beta-catenin pathway in endometrial cells, which may together
      participate in the occurrence of endometriosis.

PMID- 29018949
TI  - The corticospinal responses of metronome-paced, but not self-paced strength
      training are similar to motor skill training.
AB  - PURPOSE: The corticospinal responses to skill training may be different to
      strength training, depending on how the strength training is performed. It was
      hypothesised that the corticospinal responses would not be different following
      skill training and metronome-paced strength training (MPST), but would differ
      when compared with self-paced strength training (SPST). METHODS: Corticospinal
      excitability, short-interval intra-cortical inhibition (SICI) and strength and
      tracking error were measured at baseline and 2 and 4 weeks. Participants (n = 44)
      were randomly allocated to visuomotor tracking, MPST, SPST or a control group.
      RESULTS: MPST increased strength by 7 and 18%, whilst SPST increased strength by
      12 and 26% following 2 and 4 weeks of strength training. There were no changes in
      strength following skill training. Skill training reduced tracking error by 47
      and 58% at 2 and 4 weeks. There were no changes in tracking error following SPST;
      however, tracking error reduced by 24% following 4 weeks of MPST. Corticospinal
      excitability increased by 40% following MPST and by 29% following skill training.
      There was no change in corticospinal excitability following 4 weeks of SPST.
      Importantly, the magnitude of change between skill training and MPST was not
      different. SICI decreased by 41 and 61% following 2 and 4 weeks of MPST, whilst
      SICI decreased by 41 and 33% following 2 and 4 weeks of skill training. Again,
      SPST had no effect on SICI at 2 and 4 weeks. There was no difference in the
      magnitude of SICI reduction between skill training and MPST. CONCLUSIONS: This
      study adds new knowledge regarding the corticospinal responses to skill and MPST,
      showing they are similar but different when compared with SPST.

PMID- 29018950
TI  - Are viviparous lizards more vulnerable to climate warming because they have
      evolved reduced body temperature and heat tolerance?
AB  - Lizards may experience population declines and extinctions on a similar scale to
      that experienced by amphibians, and climate warming is one hypothesis proposed to
      explain these declines and extinctions. Within lizards, viviparous species are
      hypothesized to be more vulnerable to climate warming, because they have evolved
      reduced body temperature and heat tolerance, but this idea remains untested. To
      test this hypothesis, we conducted three temperatures (20, 24, and 28  degrees C)
      * two species [Phrynocephalus przewalskii (oviparous) and P. putjatia
      (viviparous)] factorial design experiment that simulated warming on oviparous
      versus viviparous lizards. Our manipulation of ambient temperature affected
      activity and thermal preference in both species, birth date in P. putjatia, and
      egg mass in P. przewalskii; other examined traits (fecundity, reproductive
      output, and size, morphology, and sprint speed of offspring) were not affected.
      Neither in P. putjatia nor in P. przewalskii behavioral responses to rising
      temperatures differ between the sexes. The viviparous species thermoregulated
      more actively than did the oviparous species, but the two species did not differ
      in thermal preference. Warming reduced the activity time allotted for
      thermoregulation in both species, but the effect was more dramatic in the
      viviparous species. Our data support one of the central predictions that lead to
      the hypothesis that viviparous lizards are more vulnerable to climate warming;
      however, this is not because viviparous lizards have evolved reduced body
      temperature and heat tolerance, but, because warming constrains activity more
      dramatically in viviparous species.

PMID- 29018951
TI  - The role of the mating system and intraspecific brood parasitism in the costs of
      reproduction in a passerine bird.
AB  - Limited resources trigger trade-offs in resource allocation. Reproduction is one
      of the most demanding activities in terms of energy, and costs related to
      reproduction can be apparent either as reduced future reproduction or as
      survival. However, costs are not always detected, because individual
      heterogeneity in quality and resource acquisition may explain variation in costs
      among individuals. We conducted a comprehensive study in spotless starlings
      (Sturnus unicolor) nesting in Central Spain to determine whether costs of
      reproduction could be detectable in the short and/or long term and whether
      prenatal or postnatal investment were driving these costs. We took into account
      the life history of the species, where egg volume is highly repeatable, males are
      facultatively polygynous, and intraspecific brood parasitism occurs. Females with
      a high reproductive effort in a breeding event also had a high reproductive
      effort in the second event of the season. The mating system and maternal age were
      reliable predictors of breeding success within a breeding event: monogamous and
      primary females, as well as older mothers, raised more nestlings than secondary
      females and 1-year-old females, respectively. However, when high-investing
      females suffered intra-brood parasitism in 1 year, we found a negative
      correlation between current and future reproduction. These results suggest that,
      under some circumstances, females are able to skip the short-term costs of
      reproduction, but when extra effort is added, trade-offs arise. While most
      studies have focused on different aspects of individual quality on costs, the
      ecological context seems to represent an important component that should be taken
      into account.

PMID- 29018952
TI  - Automated breast volume scanner (ABVS) in assessing breast cancer size: A
      comparison with conventional ultrasound and magnetic resonance imaging.
AB  - OBJECTIVES: To compare automated breast volume scanner (ABVS), ultrasound (US)
      and MRI in measuring breast cancer size, and evaluate the agreement between ABVS
      and US in assessing lesion location and sonographic features. METHODS: We
      retrospectively included 98 women with 100 index cancers who had undergone US and
      ABVS followed by 1.5T MRI. Images were interpreted by a pool of readers reporting
      lesion size, location and breast imaging reporting and data system (BI-RADS)
      features. Bland-Altman analysis (with logarithmic data transformation),
      intraclass correlation coefficient (ICC) and Cohen's kappa statistic were used
      for statistical analysis. RESULTS: MRI showed the best absolute agreement with
      histology in measuring cancer size (ICC 0.93), with LOA comparable to those of
      ABVS (0.63-1.99 vs. 0.52-1.73, respectively). Though ABVS and US had highly
      concordant measurements (ICC 0.95), ABVS showed better agreement with histology
      (LOA 0.52-1.73 vs. 0.45-1.86, respectively), corresponding to a higher ICC (0.85
      vs. 0.75, respectively). Except for posterior features (k=0.39), the agreement
      between US and ABVS in attributing site and BI-RADS features ranged from
      substantial to almost perfect (k=0.68-0.85). CONCLUSIONS: ABVS performs better
      than US and approaches MRI in predicting breast cancer size. ABVS performs
      comparably to US in sonographic assessment of lesions. KEY POINTS: * ABVS
      approaches MRI in predicting breast cancer size. * ABVS is equivalent to US in
      localising and characterising breast cancer. * ABVS is more accurate than US in
      assessing breast cancer size. * ABVS has the potential to replace US in breast
      cancer staging.

PMID- 29018953
TI  - Frequency and proliferative response of circulating invariant natural killer T
      cells in pediatric patients with malignant solid tumors.
AB  - BACKGROUND: Invariant natural killer T (iNKT) cells play an important role in
      tumor immunity, enhancing both innate and acquired immunity. We have previously
      shown the enhancement of antibody-dependent cellular cytotoxicity against
      neuroblastoma by activated iNKT cells. As a first step towards clinical
      application, we studied the frequency and proliferative response of circulating
      iNKT cells in children with and without cancer. METHODS: Blood samples were
      collected from 10 patients with pediatric malignant solid tumors and 11 patients
      with non-neoplastic diseases (control). The frequency of circulating iNKT cells
      was quantified by flow cytometry. Whole peripheral blood mononuclear cells were
      then stimulated with alpha-galactosylceramide (alpha-GalCer) for 7 days, and the
      expansion rate of the iNKT-cell fraction was assessed. RESULTS: The frequency of
      iNKT cells in the patients of the cancer and control group did not differ to a
      statistically significant extent. The iNKT-cell population increased after alpha
      GalCer stimulation in all cases. The iNKT cells of patients who had undergone
      intensive chemotherapy also had the potential to expand in vitro. CONCLUSIONS:
      Unlike adult cancer patients, the numbers of circulating iNKT cells were not
      decreased in pediatric cancer patients. alpha-GalCer stimulation induced a
      proliferative response in all of the patients.

PMID- 29018955
TI  - The effect of laminin-1 on enteric neural crest-derived cell migration in the
      Hirschsprung's disease mouse model.
AB  - BACKGROUND/AIM: Laminin-1 regulates neurite outgrowth in various neuronal cells.
      We have previously demonstrated that laminin-1 promotes enteric neural crest
      derived cell (ENCC) migration by using Sox10-VENUS transgenic mice, in which
      ENCCs are labeled with a green fluorescent protein, Venus. Mice lacking the
      endothelin-B receptor gene, Ednrb -/- mice, are widely used as a model for
      Hirschsprung's disease (HD). The aim of this study was to investigate the effects
      of laminin-1on ENCC migration in Sox10-VENUS+/Ednrb -/- mice, a newly created HD
      mice model. METHODS: Fetal guts were dissected on embryonic day 12.5 (E12.5).
      Specimens were incubated either with, or without laminin-1 for 24 h and images
      were taken under a stereoscopic microscope. The length from the stomach to the
      wavefront of ENCC migration (L-E) and the total length of the gut (L-G) were
      measured. Changes in the ratio of L-E to L-G (L-E/L-G) after 24 h were
      calculated. RESULTS: On E12.5, the wavefront of ENCC migration in the HD gut
      samples was located in the midgut, whereas the wavefront of ENCC in Sox10
      VENUS+/Ednrb +/+ (WT) samples had reached the hindgut. After 24 h, L-E/L-G had
      increased by 1.49%, from 34.97 to 36.46%, in HD gut and had increased by 1.07%,
      from 48.08 to 49.15%, in HD with laminin-1, suggesting there was no positive
      effect of laminin-1 administration on ENCC migration in HD. CONCLUSIONS: Our
      results suggest that laminin-1 does not have a positive effect on ENCC migration
      in HD mice on E12.5, in contrast to the phenomenon seen in normal mice gut
      specimens, where laminin-1 promotes ENCC migration during the same period. This
      suggests that there is an impairment in the interaction between ENCC and
      extracellular environmental factors, which are required for normal development of
      the enteric nervous system, resulting in an aganglionic colon in HD.

PMID- 29018954
TI  - The importance of cutaneous feedback on neural activation during maximal
      voluntary contraction.
AB  - PURPOSE: The purpose of this study was to investigate the importance of cutaneous
      feedback on neural activation during maximal voluntary contraction (MVC) of the
      ankle plantar flexors. METHODS: The effects of cutaneous plantar anaesthesia were
      assessed in 15 subjects and compared to 15 controls, using a one-day pre/post
      repeated measures design. Cutaneous plantar anaesthesia was induced by lidocaine
      injection at the centre of forefoot, lateral midfoot, and heel. Each subject
      performed isometric MVCs of the ankle plantar flexors. During each isometric ramp
      contraction, the following variables were assessed: maximal isometric torque;
      surface electromyography (EMG) activity of the medial gastrocnemius (MG) and
      tibialis anterior (TA) muscles; and co-contraction index (CCI) between the MG and
      TA. RESULTS: For ankle torque, two-way ANOVA showed no significant interaction
      between the pre/post-measurements * group (p = 0.166). However, MG activity
      presented significant interactions between the pre/post-measurements * group (p =
      0.014). Post hoc comparisons indicated a decrease of MG activity in the
      experimental group, from 85.9 +/- 11.9 to 62.7 +/- 30.8% (p = 0.016).
      Additionally, the post-anaesthesia MG activity of the experimental group differed
      statistically with pre- and post-MG activity of the control group (p = 0.027 and
      p = 0.008, respectively). For TA activity and CCI, two-way ANOVA detected no
      significant interactions between the pre/post-measurements * group (p = 0.605 and
      p = 0.332, respectively). CONCLUSION: Our results indicate that during MVC,
      cutaneous feedback modulates neural activity to MG muscle, without changing the
      extent of MG-TA co-contraction.

PMID- 29018957
TI  - Effect of heat stress on production and in-vitro antioxidant activity of
      polysaccharides in Ganoderma lucidum.
AB  - Ganoderma lucidum is a traditional Chinese medicine, and its polysaccharides
      possess diverse and significant pharmacological activities. This study aimed to
      investigate the polysaccharide production, molecular characteristics and in-vitro
      antioxidant activity of G. lucidum fruiting body after the mushroom was harvested
      and treated with heat stress (HS). HS enhanced the production of polysaccharides
      after harvest and treatment of 42  degrees C HS for 2 h, and that resulted in the
      highest polysaccharide yield of 10.50%, which was 45.63% higher than that of the
      control, while 37, 45  degrees C HS had no significant effect on the production.
      In terms of molecular characteristics, 42  degrees C HS significantly changed
      monosaccharide ratio of polysaccharides, but no apparent molecular weight and
      functional group changes were found in polysaccharides after HS treatment. The
      results of in-vitro antioxidant activity assay revealed that 42  degrees C HS
      significantly improved the antioxidant activities of polysaccharides at the
      concentration of 2 mg/mL. In conclusion, this study provides a promising strategy
      to improve the production of G. lucidum fruiting body polysaccharides.

PMID- 29018956
TI  - Remote kinematic training for patients with chronic neck pain: a randomised
      controlled trial.
AB  - PURPOSE: To evaluate short- and intermediate-term effects of kinematic training
      (KT) using virtual reality (VR) or laser in patients with chronic neck pain.
      METHODS: A randomised controlled trial with three arms (laser, VR, control) to
      post-intervention (N = 90), and two arms (laser or VR) continuing to 3 months
      follow-up. Home training intervention was provided during 4 weeks to VR and laser
      groups while control group waited. OUTCOME MEASURES: Primary outcome measures
      included neck disability index (NDI), global perceived effect (GPE), and cervical
      motion velocity (mean and peak). Secondary outcome measures included pain
      intensity (VAS), health status (EQ5D), kinesiophobia (TSK), range, smoothness,
      and accuracy of neck motion as measured by the neck VR system. Measures were
      taken at baseline, immediately post-training, and 3 months later. RESULTS: Ninety
      patients with neck pain were randomised to the trial, of which 76 completed 1
      month follow-up, and 56 the 3 months follow-up. Significant improvements were
      demonstrated in NDI and velocity with good effect sizes in intervention groups
      compared to control. No within-group changes were presented in the control group,
      compared to global improvements in intervention groups. Velocity significantly
      improved at both time points in both groups. NDI, VAS, EQ5D, TSK and accuracy
      significantly improved at both time points in VR and in laser at 3 months
      evaluation in all but TSK. GPE scores showed 74-84% of participants perceived
      improvement and/or were satisfied. Significant advantages to the VR group
      compared to laser were found in velocity, pain intensity, health status and
      accuracy at both time points. CONCLUSION: The results support home kinematic
      training using VR or laser for improving disability, neck pain and kinematics in
      the short and intermediate term with an advantage to the VR group. The results
      provide directions for future research, use and development. TRIAL REGISTRATION:
      ACTRN12615000231549.

PMID- 29018958
TI  - Comparison of virtual monoenergetic and polyenergetic images reconstructed from
      dual-layer detector CT angiography of the head and neck.
AB  - OBJECTIVES: To compare the image quality of virtual monoenergetic images and
      polyenergetic images reconstructed from dual-layer detector CT angiography
      (DLCTA). METHODS: Thirty patients who underwent DLCTA of the head and neck were
      retrospectively identified and polyenergetic as well as virtual monoenergetic
      images (40 to 120 keV) were reconstructed. Signals (+/- SD) of the cervical and
      cerebral vessels as well as lateral pterygoid muscle and the air surrounding the
      head were measured to calculate the CNR and SNR. In addition, subjective image
      quality was assessed using a 5-point Likert scale. Student's t-test and Wilcoxon
      test were used to determine statistical significance. RESULTS: Compared to
      polyenergetic images, although noise increased with lower keV, CNR (p < 0.02) and
      SNR (p > 0.05) of the cervical, petrous and intracranial vessels were improved in
      virtual monoenergetic images at 40 keV and virtual monoenergetic images at 45 keV
      were also rated superior regarding vascular contrast, assessment of arteries
      close to the skull base and small arterial branches (p < 0.0001 each).
      CONCLUSIONS: Compared to polyenergetic images, virtual monoenergetic images
      reconstructed from DLCTA at low keV ranging from 40 to 45 keV improve the
      objective and subjective image quality of extra- and intracranial vessels and
      facilitate assessment of vessels close to the skull base and of small arterial
      branches. KEY POINTS: * Virtual monoenergetic images greatly improve attenuation,
      while noise only slightly increases. * Virtual monoenergetic images show superior
      contrast-to-noise ratios compared to polyenergetic images. * Virtual
      monoenergetic images significantly improve image quality at low keV.

PMID- 29018959
TI  - Invariant natural killer T infiltration in neuroblastoma with favorable outcome.
AB  - BACKGROUND: Tumor immunity has been suggested to play a key role in clinical and
      biological behavior of neuroblastomas. Given that CD1-restricted invariant
      natural killer T (iNKT) cells enhance both innate and acquired tumor immunity, we
      investigated the expression of the iNKT-cell-specific T-cell receptor Valpha24
      Jalpha18 in neuroblastoma tissues and its correlation with clinical and
      biological characteristics. METHODS: Using real- time quantitative PCR, we
      quantified the expression of Valpha24-Jalpha18 in untreated tumor samples from
      107 neuroblastoma cases followed in our institution and analyzed the correlation
      between the presence of infiltrated iNKT cells and clinical characteristics or
      patients' outcome. RESULTS: Valpha24-Jalpha18 receptor was detected in 62
      untreated cases (57.9%). The expression was significantly higher in stages 1, 2,
      3, or 4S (P = 0.0099), in tumors with low or intermediate risk (P = 0.0050), with
      high TrkA expression (P = 0.0229), with favorable histology (P = 0.0026), with
      aneuploidy (P = 0.0348), and in younger patients (P = 0.0036). The overall
      survival rate was significantly higher in patients with iNKT-cell infiltration
      (log-rank; P = 0.0089). CONCLUSIONS: Since tumor-infiltrating iNKT cells were
      predominantly observed in neuroblastomas undergoing spontaneous differentiation
      and/or regression, we suggest that iNKT cells might play a key role in these
      processes.

PMID- 29018961
TI  - Accuracy of a patient-specific template for pedicle screw placement compared with
      a conventional method: a meta-analysis.
AB  - INTRODUCTION: Accurate placement of pedicle screws in spine surgery is a
      challenge for surgeons. Patient-specific template techniques have the potential
      for improving the accuracy of screw placement. The target of this analysis was to
      investigate differences in terms of accuracy of pedicle screw insertion between
      patient-specific template assistance and the conventional free-hand method for
      reconstruction of spinal stability. MATERIALS: The Cochrane Library, Ovid, Web of
      Science, PubMed, EMBASE and CNKI database were searched until February 2017 for a
      systematic review, and several comparative studies were screened for comparisons
      of accuracies of pedicle screw insertion with patient-specific assistance and
      conventional methods. Primary outcomes extracted from papers that met the
      selection criterion were expressed as odds ratios for dichotomous outcomes with a
      95% confidence interval. A chi 2 test and I 2 statistics were used to evaluate
      heterogeneity. RESULTS: A total of ten RCTs and two prospective cohort studies
      were finally chosen for the analysis of accuracy rates. Study quality was
      assessed using the Cochrane Collaboration's Tool and Newcastle-Ottawa Quality
      Assessment Scale. There were obvious differences between them, and the accuracy
      rate of screw implantation among a patient-specific template assistance set was
      statistically significantly higher than the conventional free-hand set (OR 95% CI
      3.78-6.41, P < 0.01); in vitro: OR 95% CI 3.93-7.42, P < 0.01; in vivo: OR 95% CI
      2.49-6.44, P < 0.01. CONCLUSIONS: The template-assisted technique is superior to
      the conventional method for the reduction of pedicle violation. The template
      assisted technique is a promising technique that should be considered as another
      available navigation tool for surgeons to improve the accuracy of pedicle screw
      placement. As an available technique for emerging applications in spine
      surgeries, this technique will face challenges but ultimately prove successfully.

PMID- 29018960
TI  - Influence of stress factors on intestinal epithelial injury and regeneration.
AB  - PURPOSE: Lgr5+ intestinal epithelial stem cells (ISCs) crucial for intestinal
      epithelial regeneration are impaired during necrotizing enterocolitis. This study
      aims to investigate the influence of different stressors on intestinal epithelial
      injury and regeneration in vitro. METHODS: Intestinal epithelial cells (IEC-18)
      were exposed to stressors such as lipopolysaccharide, hydrogen peroxide, and
      serum. Cell viability was assessed using MTT assay at 18 and 24 h. IL-6 and Lgr5
      gene expressions were measured using qPCR. RESULTS: IEC-18 cell viability
      decreased 18 h following administration of lipopolysaccharide, hydrogen peroxide,
      and low serum concentration. However, after 24 h, the decrease in cell viability
      was observed only in higher, but not in lower concentrations of
      lipopolysaccharide and hydrogen peroxide. IL-6 expression increased in all groups
      compared to control. Lgr5 expression was up-regulated in cells exposed to a
      single stressor, but down-regulated when multiple stressors were administered.
      CONCLUSION: Lipopolysaccharide, hydrogen peroxide, or low serum induced IEC-18
      injury. The upregulation of Lgr5 expression after exposure to a single stressor
      suggests that minor injury to IEC-18 induces Lgr5+ ISCs to stimulate repair.
      Conversely, when IEC-18 cells were exposed to multiple stressors, Lgr5 expression
      was reduced. We speculate that this finding is similar to what happens in NEC
      when multiple stressors cause impairment of intestinal epithelium regeneration.

PMID- 29018962
TI  - The fetal lung-to-liver signal intensity ratio on magnetic resonance imaging as a
      predictor of outcomes from isolated congenital diaphragmatic hernia.
AB  - PURPOSE: We investigated the developmental changes in the unaffected
      contralateral lungs of patients with isolated left-sided congenital diaphragmatic
      hernia (CDH) using signal intensity ratios on prenatal magnetic resonance imaging
      (MRI) and determined whether these changes correlated with clinical outcomes.
      METHODS: We performed 47 fetal MRI screens on 30 patients with isolated left
      sided CDH. A cohort of 88 fetuses was selected as the control. We calculated the
      lung-to-liver signal intensity ratio (LLSIR) using region of interest analysis
      and compared LLSIR between the groups and between those in the CDH group with
      good and poor prognoses. RESULTS: In the control group, LLSIR increased as
      pregnancy progressed [regression line = 2.232 + 0.135 * (GW-23), r = 0.669]. In
      the CDH group, especially in the poor prognosis group, LLSIR did not
      significantly increase as pregnancy progressed [regression line for good
      prognosis = 1.827 + 0.092 * (gestational week-23), r = 0.733; regression line for
      poor prognosis = 1.731 + 0.025 * (gestational week-23), r = 0.634]. CONCLUSION:
      Fetal LLSIR on T2-weighted MRI is an accurate marker of fetal lung maturity that
      correlates with postnatal survival and can potentially be used as a prognostic
      parameter in CDH management.

PMID- 29018963
TI  - Molecular analysis of the low-temperature Escherichia coli phage vB_EcoS_NBD2.
AB  - A novel low-temperature Escherichia coli phage vB_EcoS_NBD2 was isolated in
      Lithuania from agricultural soil. With an optimum temperature for plating around
      20  degrees C, vB_EcoS_NBD2 efficiently produced plaques on Escherichia coli
      NovaBlue (DE3) at a temperature range of 10-30  degrees C, yet failed to plate at
      temperatures above 35  degrees C. Phage vB_EcoS_NBD2 virions have a siphoviral
      morphology with an isometric head (65 nm in diameter), and a non-contractile
      flexible tail (170 nm). The 51,802-bp genome of vB_EcoS_NBD2 has a G + C content
      of 49.8%, and contains 87 probable protein-encoding genes as well as 1 gene for
      tRNASer. Comparative sequence analysis revealed that 22 vB_EcoS_NBD2 ORFs encode
      unique proteins that have no reliable identity to database entries. Based on
      homology to biologically defined proteins and/or proteomics analysis, 36
      vB_EcoS_NBD2 ORFs were given a putative functional annotation, including 20 genes
      coding for morphogenesis-related proteins and 13 associated with DNA metabolism.
      Phylogenetic analysis revealed that vB_EcoS_NBD2 belongs to the subfamily
      Tunavirinae, but cannot be assigned to any genus currently recognized by ICTV.

PMID- 29018964
TI  - A method to quantify the "cone of economy".
AB  - STUDY DESIGN: A non-randomized, prospective, concurrent control cohort study.
      OBJECTIVE: The purpose of this study is to develop and evaluate a method to
      quantify the dimensions of the cone of economy (COE) and the energy expenditure
      associated with maintaining a balanced posture within the COE, scoliosis patients
      and compare them to matched non-scoliotic controls in a group of adult
      degenerative. Balance is defined as the ability of the human body to maintain its
      center of mass (COM) within the base of support with minimal postural sway. The
      cone of economy refers to the stable region of upright standing posture. The
      underlying assumption is that deviating outside one's individual cone challenges
      the balance mechanisms. Adult degenerative scoliosis (ADS) patients exhibit a
      variety of postural changes within their COE, involving the spine, pelvis and
      lower extremities, in their effort to compensate for the altered posture.
      METHODS: Ten ADS patients and ten non-scoliotic volunteers performed a series of
      functional balance tests. The dimensions of the COE and the energy expenditure
      related to maintaining balance within the COE were measured using a human motion
      video capture system and dynamic surface electromyography. RESULTS: ADS patients
      presented more COM sway in the sagittal (ADS: 1.59 cm vs. H: 0.61 cm; p = 0.049)
      and coronal (ADS: 2.84 cm vs. H: 1.72 cm; p = 0.046) directions in comparison to
      the non-scoliotic control. ADS patients presented with more COM (ADS: 33.30 cm
      vs. H: 19.13 cm; p = 0.039) and head (ADS: 31.06 cm vs. H: 19.13 cm; p = 0.013)
      displacements in comparison to the non-scoliotic controls. Scoliosis patients
      expended more muscle activity to maintain static standing, as manifest by
      increased muscle activity in their erector spinae (ADS: 37.16 mV vs. H: 20.31 mV;
      p = 0.050), and gluteus maximus (ADS: 33.12 mV vs. H: 12.09 mV; p = 0.001)
      muscles. CONCLUSIONS: We were able to develop and evaluate a method that
      quantifies the COE boundaries, COM displacement, and amount of sway within the
      COE along with the energy expenditure for a specific patient. This method of COE
      measurement will enable spine care practitioners to objectively evaluate their
      patients in an effort to determine the most appropriate treatment options, and in
      objectively documenting the effectiveness of their intervention.

PMID- 29018965
TI  - The role of maintenance therapy in eosinophilic esophagitis: who, why, and how?
AB  - In patients with eosinophilic esophagitis (EoE) who do not respond to proton pump
      inhibitors, initial anti-inflammatory/anti-eosinophilic treatment is with either
      topical corticosteroids or dietary elimination. A large body of literature
      supports the efficacy of these approaches, with histologic response rates in the
      50-90% range for steroids and 70% range for the six-food elimination diet.
      However, these studies are almost all short-term and data evaluating long-term
      safety and efficacy of either treatment are limited. Nevertheless, because EoE is
      chronic, symptomatic, endoscopic, and histologic disease activity recurs when
      successful treatments are stopped. An emerging body of data also suggest that
      left untreated, persistent eosinophilic esophageal inflammation may progress to
      fibrostenosis over time. Therefore, maintenance therapy in EoE is intuitively
      attractive. This paper reviews the rationale for maintenance treatment in EoE,
      the available long-term pharmacologic and dietary response data for EoE, and
      discusses who may benefit the most from ongoing treatment. While all patients
      with EoE can be offered maintenance treatment, this option should be strongly
      recommended in patients with severe disease phenotypes or complications,
      including malnutrition or failure to thrive, esophageal fibrostenosis, strictures
      requiring dilation, recurrent food bolus impaction, history of perforation, and
      symptoms that recur quickly after treatment discontinuation. In all EoE patients,
      regular follow-up is also advised.

PMID- 29018966
TI  - Safety and cost benefit of an ambulatory program for patients with low-risk
      neutropenic fever at an Australian centre.
AB  - BACKGROUND: Neutropenic fever (NF) is a common complication of cancer
      chemotherapy. Patients at low risk of medical complications from NF can be
      identified using a validated risk assessment and managed in an outpatient
      setting. This is a new model of care for Australia. This study described the
      implementation of a sustainable ambulatory program for NF at a tertiary cancer
      centre over a 12-month period. METHODS: Peter MacCallum Cancer Centre introduced
      an ambulatory care program in 2014, which identified low-risk NF patients,
      promoted early de-escalation to oral antibiotics, and early discharge to a nurse
      led ambulatory program. Patients prospectively enrolled in the ambulatory program
      were compared with a historical-matched cohort of patients from 2011 for
      analysis. Patient demographics, clinical variables (cancer type, recent
      chemotherapy, treatment intent, site of presentation) and outcomes were collected
      and compared. Total cost of inpatient admissions was determined from diagnosis
      related group (DRG) codes and applied to both the prospective and historical
      cohorts to allow comparisons. RESULTS: Twenty-five patients were managed in the
      first year of this program with a reduction in hospital median length of stay
      from 4.0 to 1.1 days and admission cost from Australian dollars ($AUD) 8580 to
      $AUD2360 compared to the historical cohort. Offsetting salary costs, the
      ambulatory program had a net cost benefit of $AUD 71895. Readmission for fever
      was infrequent (8.0%), and no deaths were reported. CONCLUSION: Of relevance to
      hospitals providing cancer care, feasibility, safety, and cost benefits of an
      ambulatory program for low-risk NF patients have been demonstrated.

PMID- 29018967
TI  - Mitigating arsenic contamination in rice plants with an aquatic fern, Marsilea
      minuta.
AB  - Dangers of arsenic contamination are well known in human civilization. The threat
      increases when arsenic is accumulated in food and livestock through irrigated
      crops or animal food. Hence, it is important to mitigate the effects of arsenic
      as much as possible. This paper discusses a process for reducing the level of
      arsenic in different parts of rice plants with an aquatic fern, Marsilea minuta
      L. A pot experiment was done to study the possibility of using Marsilea minuta as
      a phytoremediator of arsenic. Rice and Marsilea minuta were allowed to grow
      together in soils. As a control, Marsilea minuta was also cultured alone in the
      presence and absence of arsenic (applied at 1 mg/L as irrigation water). We did
      not find any significant change in the growth of rice due to the association of
      Marsilea minuta, though it showed a reduction of approximately 58.64% arsenic
      accumulation in the roots of rice grown with the association of fern compared to
      that grown without fern. We measured a bioaccumulation factor (BF) of > 5.34,
      indicating that Marsilea minuta could be a good phytoremediator of arsenic in
      rice fields.

PMID- 29018968
TI  - Determination of the complete genomic sequence of grapevine virus H, a novel
      vitivirus infecting grapevine.
AB  - The present work reports the discovery and the complete genome sequencing of a
      novel member of the genus Vitivirus in the family Betaflexiviridae (subfamily
      Trivirinae) from a symptomless grapevine of unknown variety from Portugal. Total
      RNAs extracted from phloem scrapings were sequenced using Illumina technology.
      Bioinformatic analysis of the RNA-seq data revealed a mixed infection involving
      three viruses and two viroids in addition to a novel vitivirus. Completion and
      analysis of the genome sequence (7446 nt excluding the polyA tail) showed a
      typical vitivirus genomic organization. Phylogenetic analysis of the various ORFs
      clearly showed the new virus to belong in the genus Vitivirus, but sequence
      divergence firmly establishes it as a member of a new species, for which the name
      "Grapevine virus H" is proposed.

PMID- 29018969
TI  - Biomineralisation of carbonate and sulphate by the halophilic bacterium Halomonas
      maura at different manganese concentrations.
AB  - The ability of Halomonas maura to bioprecipitate carbonate and sulphate crystals
      in solid media at different manganese concentrations has been demonstrated in
      this study for the first time. The precipitated minerals were studied by X-ray
      diffraction, scanning and transmission electron microscopy, and energy-dispersive
      X-ray spectroscopy. The precipitated minerals were different based on the
      manganese concentration present in the medium and the incubation time. In the
      absence of manganese, H. maura formed pseudokutnahorite crystals; in the presence
      of manganese, the concentration in the culture medium determined the
      precipitation carbonates, such as rhodochrosite and dolomites. However, in the
      presence of low concentrations of manganese chloride (MnCl2) (5 g/l), kutnohorite
      crystals were also formed. Finally, when H. maura was grown in the presence of
      manganese, small amounts of sulphate crystals (such as bassanite and gypsum) were
      detected. Our study of the precipitated minerals showed an active role of H.
      maura in the biomineralisation process, but the geochemical conditions, and the
      manganese concentrations in particular, were clearly influential.

PMID- 29018970
TI  - Andersen's syndrome mutants produce a knockdown of inwardly rectifying K+ channel
      in mouse skeletal muscle in vivo.
AB  - Andersen's syndrome (AS) is a rare autosomal disorder that has been defined by
      the triad of periodic paralysis, cardiac arrhythmia, and developmental anomalies.
      AS has been directly linked to over 40 different autosomal dominant negative loss
      of-function mutations in the KCNJ2 gene, encoding for the tetrameric strong
      inward rectifying K+ channel KIR2.1. While KIR2.1 channels have been suggested to
      contribute to setting the resting membrane potential (RMP) and to control the
      duration of the action potential (AP) in skeletal and cardiac muscle, the
      mechanism by which AS mutations produce such complex pathophysiological symptoms
      is poorly understood. Thus, we use an adenoviral transduction strategy to study
      in vivo subcellular distribution of wild-type (WT) and AS-associated mutant
      KIR2.1 channels in mouse skeletal muscle. We determined that WT and D71V AS
      mutant KIR2.1 channels are localized to the sarcolemma and the transverse tubules
      (T-tubules) of skeletal muscle fibers, while the ?314-315 AS KIR2.1 mutation
      prevents proper trafficking of the homo- or hetero-meric channel complexes. Whole
      cell voltage-clamp recordings in individual skeletal muscle fibers confirmed the
      reduction of inwardly rectifying K+ current (IK1) after transduction with ?314
      315 KIR2.1 as compared to WT channels. Analysis of skeletal muscle function
      revealed reduced force generation during isometric contraction as well as reduced
      resistance to muscle fatigue in extensor digitorum longus muscles transduced with
      AS mutant KIR2.1. Together, these results suggest that KIR2.1 channels may be
      involved in the excitation-contraction coupling process required for proper
      skeletal muscle function. Our findings provide clues to mechanisms associated
      with periodic paralysis in AS.

PMID- 29018971
TI  - CSF RBC count in successful first-attempt lumbar puncture: the interest of
      atraumatic needle use.
AB  - The objective of this study is to analyze CSF red blood cell (RBC) count from
      first-attempt lumbar punctures and to analyze parameters associated with first
      attempt lumbar punctures and hemorrhagic lumbar puncture. This is a prospective
      analysis of consecutive patients who underwent lumbar puncture for any reason
      other than suspected acute subarachnoid hemorrhage. Analyzed parameters were the
      following: age, indication for lumbar puncture, aPTT ratio, PTT, platelet count,
      patient's position, needle type (atraumatic/standard), needle diameter, person
      performing lumbar puncture (medical student/resident/attending physician), number
      of lumbar levels punctured, necessity of needle repositioning, CSF RBC and white
      blood cell count, and protein level. Lumbar puncture resulting in RBC count > 5
      RBC/mm2 was classified as hemorrhagic lumbar puncture (different cut-offs were
      studied: > 5/> 10/> 100/> 500/> 1000 RBC). In total, 169 elective lumbar
      punctures in 165 different patients were included. First-attempt lumbar puncture
      occurred in 22% > 5 RBC, in 19.5% > 10 RBC, in 4.5% > 100 RBC, in 3% > 500 RBC,
      and 1.5% > 1000 RBC count. First-attempt lumbar puncture was associated with non
      hemorrhagic lumbar puncture for each of the RBC count cut-offs (OR for non
      hemorrhagic lumbar puncture in first-attempt lumbar puncture 2.8, 95% CI 1.4
      5.7). The presence of a hemorrhagic disorder (concerning cerebral amyloid
      angiopathy in all patients) and higher aPTT ratio were associated with
      hemorrhagic lumbar puncture. Atraumatic needle use was associated with non
      hemorrhagic lumbar puncture for RBC count cut-offs <= 5 and <= 10 RBC (OR for non
      hemorrhagic lumbar puncture in atraumatic needle use 2.5 [95% CI 1.3-4.8] and 2.2
      [95% CI 1.1-4.4], respectively). First-attempt lumbar puncture and hemorrhagic
      lumbar puncture were not associated with other parameters. Slightly elevated CSF
      RBC count after first-attempt lumbar puncture occurs relatively frequently, but
      is even more frequent in non-first-attempt lumbar puncture. Atraumatic needle use
      is associated with non-hemorrhagic lumbar puncture.

PMID- 29018972
TI  - Birth management and fetal outcome in multiple gestation: analysis of 1.444
      births.
AB  - PURPOSE: Since the late 1990s, controversies came up concerning the mode of
      delivery for multiples births. The twin birth study indicated no difference in
      maternal and fetal outcome between planned vaginal delivery and planned caesarean
      section, but did not analyze the influence of maternal and fetal characteristics
      or the obstetric management in vaginal birth. The purpose of this study is to
      analyze these parameters regarding fetal outcome. METHODS: A large-scale
      retrospective analysis of twin births (n = 1.444) was performed at a university
      medical center. The analysis included pregnancy, delivery, and maternal and fetal
      parameters, including pH and base excess (BE) differences between the first- and
      second-born twin (delta pH, delta BE). RESULTS: Delta pH correlated significantly
      with the birth interval for various positions of twins in the womb (p < 0.05).
      The longer the birth interval, the greater the delta pH with a lower pH of the
      second twin. Delta BE values were significantly correlated with the birth
      interval for a combination of twins in cephalic and breech presentation.
      Furthermore, it could be shown that higher differences in birth weight between
      the first/second twin are associated with higher delta pH, higher delta BE values
      (all p < 0.05). We found significantly decreasing delta pH values in vaginal
      deliveries over secondary and, finally, primary caesarean sections (p < 0.001).
      CONCLUSION: We conclude a vaginal delivery of twin appears safe if experienced
      staff monitor birth weight discrepancies, birth interval, and blood values
      consequently. A good outcome also for the second twin delivered spontaneously is
      nevertheless feasible if experienced staff is available.

PMID- 29018973
TI  - Clinical significance of fecal calprotectin for the early diagnosis of abdominal
      type of Henoch-Schonlein purpura in children.
AB  - The objective of this study is to explore the value of fecal calprotectin (FC)
      for early screening of the abdominal type of Henoch-Schonlein purpura (AHSP) in
      children. The study cohort included 40 children with AHSP treated at Shengjing
      Hospital of China Medical University from November 2014 to November 2015, and 40
      children hospitalized in the Division of Pediatric Orthopedics in the
      corresponding period were selected as a control group. Fresh fecal samples were
      collected in the acute phase of the first visit (FC1), 3 days after treatment
      (FC2), and 7 days after treatment (FC3) from the AHSP group and the control
      group. Calprotectin levels in the fecal samples were measured using an enzyme
      linked immunosorbent assay. At the same time, gastrointestinal performance and
      the laboratory examination indicators white blood cell (WBC) count and C-reactive
      protein (CRP) level were recorded. The median levels of FC1 (3053 MUg/g) and FC2
      (2778.3 MUg/g) were higher than in the control group (102.5 MUg/g), with
      significant differences among the three groups (p < 0.001). FC levels gradually
      decreased in remission, and the level of FC3 on day 7 was close to that of the
      control samples (p > 0.05). When the optimal cut-off was 264.5 MUg/g, the area
      under the receiver operating characteristic (ROC) curve of FC for diagnosis of
      AHSP was 0.961 with a corresponding sensitivity and specificity of 93.1 and
      87.5%, respectively. The levels of FC in children with AHSP were positively
      correlated with WBC count (r s = 0.688) and CRP value (r s = 0.513). The area
      under the ROC curve of WBC count for screening AHSP was 0.785 when the optimal
      cut-off value was 11.1 * 109/L with a corresponding sensitivity and specificity
      of 81.5 and 62.5%, respectively. The area under the ROC curve of CRP was 0.963
      when the optimal cut-off value was 5.72 mg/dL with a corresponding sensitivity
      and specificity of 88.9 and 100%, respectively. Comparisons of FC, WBC count, and
      CRP level as diagnostic indicators of AHSP showed that the sensitivity of FC was
      higher than that of the WBC count and CRP level, and its diagnostic value was
      better than that of the WBC count. The levels of FC began to increase in the
      early stages of AHSP, showing a decreasing tendency in remission and tending to
      be within a normal range after a week or so. For the early diagnosis of AHSP, FC
      with a cut-off level of 264.5 MUg/g has good sensitivity and specificity. The
      sensitivity of FC is better than that of the traditional inflammation indicators
      CRP and WBC count, and its diagnostic performance is better than WBC count; FC
      can be suitable as a new marker for the early diagnosis of AHSP.

PMID- 29018975
TI  - Progressive anterior operculum syndrome due to frontotemporal lobar degeneration.

PMID- 29018974
TI  - Catalytic diversity and homotropic allostery of two Cytochrome P450 monooxygenase
      like proteins from Trichoderma brevicompactum.
AB  - Trichothecenes are the secondary metabolites produced by Trichoderma spp. Some of
      these molecules have been reported for their ability to stimulate plant growth by
      suppressing plant diseases and hence enabling Trichoderma spp. to be efficiently
      used as biocontrol agents in modern agriculture. Many of the proteins involved in
      the trichothecenes biosynthetic pathway in Trichoderma spp. are encoded by the
      genes present in the tri cluster. Tri4 protein catalyzes three consecutive
      oxygenation reaction steps during biosynthesis of isotrichodiol in the
      trichothecenes biosynthetic pathway, while tri11 protein catalyzes the C4
      hydroxylation of 12, 13-epoxytrichothec-9-ene to produce trichodermol. In the
      present study, we have homology modelled the three-dimensional structures of tri4
      and tri11 proteins. Furthermore, molecular dynamics simulations were carried out
      to elucidate the mechanism of their action. Both tri4 and tri11 encode for
      cytochrome P450 monooxygenase like proteins. These data also revealed effector
      induced allosteric changes on substrate binding at an alternative binding site
      and showed potential homotropic negative cooperativity. These analyses also
      showed that their catalytic mechanism relies on protein-ligand and protein-heme
      interactions controlled by hydrophobic and hydrogen-bonding interactions which
      orient the complex in optimal conformation within the active sites.

PMID- 29018976
TI  - Capillary loss on nailfold capillary microscopy is associated with mortality in
      systemic sclerosis.
AB  - The objective of this study is to test the association of the severity of
      nailfold capillaroscopy (NFC) abnormalities with mortality in systemic sclerosis
      (SSc). One hundred and seventy SSc patients underwent an extensive evaluation
      (including high-resolution computed tomography, pulmonary function tests, and
      Doppler echocardiography) at baseline following a standard protocol. Capillary
      loss on NFC was evaluated using the avascular score (AS, ranging from 0 to 3),
      and the mean number of ectasias, megacapillaries, and hemorrhages per finger was
      also recorded. After a mean period of 10.1 +/- 4.9 years, the life status of the
      patients was ascertained. Univariate and multivariate Cox proportional hazards
      models were used for statistical analysis. Overall, 73 patients died. By
      univariate Cox analysis, the AS was significantly associated with mortality
      (hazard ratio [HR] = 1.64, 95% CI 1.22 to 2.19, p = 0.001). In our study, this
      association was stronger than that of race, gender, anticentromere antibodies,
      anti-topoisomerase I antibodies, and form of disease and had similar strength to
      that of skin score in univariate analyses. However, after controlling for a
      combination of variables (age, skin score, gender, race, signs of peripheral
      ischemia, and extent of interstitial lung disease, all independently associated
      with mortality), the association of AS with mortality was blunted (HR = 1.15, 95%
      CI 0.80 to 1.65, p = 0.445). Other NFC variables were not related to mortality.
      AS was associated with higher risk of death and, despite not having an
      independent association with mortality after controlling for a set of demographic
      and clinical variables, may be a useful tool in prognostic evaluation of SSc.

PMID- 29018977
TI  - Biodegradation of tetracycline antibiotics in A/O moving-bed biofilm reactor
      systems.
AB  - An anaerobic/aerobic moving-bed biofilm (A/O-MBBR) reactor system was
      constructed, and the treatment efficiency of aqueous antibiotics in wastewater
      was investigated. The effects of antibiotics on the microbial communities in the
      A/O-MBBR were also investigated. Under the optimized reaction conditions, removal
      of tetracycline antibiotics (TCs) was studied in a series of experiments. When a
      low concentration of tetracycline (TC) was added to the reactor system, high
      removal efficiency of conventional pollutants (TC concentration decreased from 10
      turn to 2.8 MUg L-1) was achieved. When mixed TCs (50 MUg L-1) were added to the
      system, the removal efficiencies of chlortetracycline (CTC), TC and
      oxytetracycline (OTC) reached 52.03, 41.79, and 38.42%, respectively. TC
      degradation was decreased to 21.16% when the antibiotic concentration was 500 MUg
      L-1; exposure to this TC concentration destroyed the community structure of the
      activated sludge bacteria in the reactor. The products of the biodegradation
      analysis revealed the possible degradation pathways functioning in the
      experimental A/O-MBBRs.

PMID- 29018978
TI  - Identification of ZFPM2 mutations in sporadic conotruncal heart defect patients.
AB  - Conotruncal heart defects (CTDs) are a group of cardiac malformations that
      involve outflow tract anomalies and the arterial pole of the heart. Recent
      reports have identified mutations in a number of genes associated with CTDs in
      human and animal models. ZFPM2 plays a role in cardiac development by acting as a
      transcriptional cofactor that interacts with GATA4. Because ZFPM2 was found to be
      important for cardiac development in a knockout mouse model, we screened for
      ZFPM2 mutations in 528 CTD patients. We identified six rare and nonsynonymous
      ZFPM2 variants, and this was the first time that five of these variants (R698Q,
      R736L, E1005K, T32A, and I488V) were reported in East Asians. Western blots
      showed that there was no significant difference in the protein expression of wild
      type ZFPM2, ZFPM2R698Q, or ZFPM2R736L. A dual luciferase reporter assay
      demonstrated that both ZFPM2 mutants R698Q and R736L reduced GATA4-mediated
      transcription. However, when ZFPM2R698Q was co-transfected with GATA4, BNP
      promoter activity increased significantly, whereas co-transfection with
      ZFPM2R736L and GATA4 did not significantly increase BNP promoter activity. This
      suggests that the R698Q mutation may affect the ability of ZFPM2 to bind GATA4.

PMID- 29018979
TI  - Hyperhomocysteinemia and cardiovascular disease in animal model.
AB  - Hyperhomocysteinemia is an independent risk factor for cardiovascular disease and
      is associated with primary causes of mortality and morbidity throughout the
      world. Several studies have been carried out to evaluate the effects of a diet
      inducing cystathionine-beta-synthase, methyltetrafolate, folic acid, and vitamin
      B supplemented with methionine on the homocysteine metabolism and in lowering the
      plasma total homocysteine levels. A large number of molecular and biomedical
      studies in numerous animals, such as mice, rabbits, and pigs, have sought to
      elevate the plasma total homocysteine levels and to identify a disease model for
      human hyperhomocysteinemia. However, a specific animal model is not suitable for
      hyperhomocysteinemia in terms of all aspects of cardiovascular disease. In this
      review article, the experimental progress of animal models with plasma total
      homocysteine levels is examined to identify a feasible animal model of
      hyperhomocysteinemia for different aspects.

PMID- 29018981
TI  - Diffusion coefficient in biomembrane critical pores.
AB  - Diffusion is fundamental to the random movement of solutes in solution throughout
      biological systems. Theoretical studies of diffusing solutes across cell
      membranes confined in a microscopic size of pores have been an interesting
      subject in life and medical sciences. When a solute is confined in a critical
      area of membrane pores, which shows a quite different behavior compared to the
      homogeneous-bulk fluid whose transport is isotropic in all directions. This
      property has novel features, which are of considerable physiological interest.

PMID- 29018980
TI  - Phonographic detection of mechanical heart valve thrombosis.
AB  - The formation of thrombotic deposits affects the functionality of mechanical
      prosthetic heart valves; as a consequence, mechanical valves thrombosis needs
      early diagnosis to prevent thromboembolic events. This paper compares the
      acoustic signals produced by two commercial bileaflet mechanical heart valves in
      the closing phase to detect the presence of thrombi. The closing sounds were
      recorded in vitro by means of a phonocardiographic device under different
      hydrodynamic conditions. Thrombotic deposits of different weight and shape were
      applied onto the valve leaflet and the annular housing, until the movement of one
      leaflet was completely blocked. From the acoustic signals, the corresponding
      spectra were calculated and four diagnostic frequency bands were identified:
      their comparison allowed detecting malfunctioning valves because of the presence
      of thrombotic formations.

PMID- 29018982
TI  - Estimating Emotions Through Language Statistics and Embodied Cognition.
AB  - Recent research has suggested that language processing activates perceptual
      simulations. We have demonstrated that findings that have been attributed to an
      embodied cognition account can also be explained by language statistics, because
      language encodes perceptual information. We investigated whether comprehension of
      emotion words can be explained by an embodied cognition or a language statistics
      account. A corpus linguistic study comparing emotions words showed that words
      denoting the same emotions (happy-delighted) co-occur more frequently than
      different emotions (happy-angry). These findings were used in two experiments in
      which participants read same-emotion and different-emotion sentence pairs.
      Sentence pairs with different emotions yielded longer RTs than sentences with the
      same emotions both in a cognitive task tailored toward linguistic representations
      and a task tailored toward embodied representations. These findings contribute to
      a growing body of literature that demonstrates that language processing does not
      always rely solely on perceptual simulation.

PMID- 29018985
TI  - Salinity effect on simultaneous nitrification and denitrification, microbial
      characteristics in a hybrid sequencing batch biofilm reactor.
AB  - The effect of increasing salinity on nitrogen removal via simultaneous
      nitrification and denitrification, microbial activities and extracellular
      polymeric substances (EPS) were investigated in a hybrid sequencing batch biofilm
      reactor filled with soft combination carriers. In the influent salinity range
      from 1.0 to 2.0%, average COD, NH4+-N and TN removal efficiencies were higher
      than 97.1, 97.8 and 86.4% at the steady state. When salinity was increased to 2.5
      and 3.0%, ammonium oxidation was obviously inhibited in the reactor. For both
      suspended sludge (S-sludge) and biofilm, specific ammonium oxidation rate,
      specific nitrite oxidation rate, specific oxygen uptake rate and dehydrogenase
      activity reduced with the increase of salinity. The quantity of total EPS
      increased with the increase of salinity from 1.0 to 2.0%. Generally, humic
      substances were the dominant composition of EPS in both S-sludge and biofilm,
      with the percentages of 43.9-54.0 and 43.8-64.6% in total EPS.

PMID- 29018984
TI  - Selenium status of children in Kashin-Beck disease endemic areas in Shaanxi,
      China: assessment with mercury.
AB  - The causes of Kashin-Beck disease (KBD) in children are multifactorial, and
      particular consideration has been given to childhood selenium (Se) deficiency. In
      this study, dietary intake of Se and mercury (Hg) was determined at KBD areas to
      investigate the Se status and risks. Therefore, total Hg and Se levels were
      investigated in scalp hair samples and in daily intake food samples of 150
      schoolchildren in Yongshou County of Shaanxi, China. The results showed that the
      average concentration of Se in children's hair has risen to 302 ng g-1 and
      significantly increased compared to the data reported decades ago. Children at
      KBD endemic areas likely have improved Se status due to the Se supplementation in
      food at recent decades. However, all the children in the study areas still showed
      lower Se status compared to those in other non-KBD areas of China. The probable
      daily intake of Se in the study areas was still lower after stopping Se
      supplementation in food at KBD areas, which is 17.96 MUg day-1. Food produced
      locally cannot satisfy the lowest demand for Se nutrition for local residents. If
      the interactions of Se-Hg detoxification are considered, Hg intake from food
      exacerbates Se deficiency at the KBD areas.

PMID- 29018983
TI  - Nutritional habits, risk, and progression of Parkinson disease.
AB  - Parkinson disease (PD) is a multifactorial disease, where a genetic
      predisposition combines with putative environmental risk factors. Mounting
      evidence suggests that the initial PD pathological manifestations may be located
      in the gut to subsequently affect brain areas. Moreover, several lines of
      research demonstrated that there are bidirectional connections between the
      central nervous system and the gut, the "gut-brain axis" that influences both
      brain and gastrointestinal function. This opens a potential therapeutic window
      suggesting that specific dietary strategies may interact with the disease process
      and influence the risk of PD or modify its course. Dietary components can also
      theoretically modulate the chronic activation of the inflammatory response that
      is associated with aging, the strongest risk factor for PD, that has been
      suggested to hasten the underlying neurodegenerative process in PD. Here, we
      reviewed the evidence supporting an association between certain dietary compound
      and either the risk or progression of PD and have provided an overview of the
      possible pathomechanisms linking nutrition and neurodegeneration. The results of
      our review would not support a clear role for any dietary components in reducing
      the risk or progression of PD. However, the evidence favouring a connection
      between gut abnormalities, inflammation, and neurodegeneration in PD have become
      too compelling to be ignored, so that further research, also in the field of
      nutritional genomics, is highly warranted.

PMID- 29018986
TI  - Hypokalemia during antibiotic treatment for bone and joint infections.
AB  - PURPOSE: During treatment of bone and joint infections (BJIs) with multiple
      antibiotic therapy, hypokalemia has been reported as a rare side effect. The aim
      of this study was to evaluate incidence and risk factors for hypokalemia in a
      cohort of patients treated with multidrug therapy for BJIs, in a single center.
      METHODS: We retrospectively reviewed 331 clinical files of 150 consecutive
      patients (65% males; median age 59 years, 95% CI 55-62) admitted repeatedly to
      our Osteomyelitis Department for treatment of chronic BJIs. Besides surgical
      debridement, patients received a combination of oral and intravenous antibiotics.
      Routine laboratory tests were performed at admittance and repeated at least
      weekly. Possible hypokalemia risk factors were recorded and analyzed. RESULTS:
      Progressive kalemia reduction occurred in > 39% of patients during
      hospitalization; prevalence of marked hypokalemia (K + < 3.5 mEq/l) increased
      from 5% at admission to 11% (up to 22%) at day 14. Correlated factors were: age
      >= 68 years (p = 0.033), low serum albumin (p = 0.034), treatment with vancomycin
      (p < 0.001), rifampicin (p = 0.017) and ciprofloxacin (p < 0.001) and use of
      thiazide (p = 0.007) or loop diuretics (p = 0.029 for K + < 3.5 mEq/l). At
      multivariate regression analysis, the main determinants of hypokalemia were
      simultaneous use of diuretics (p = 0.007) and older age (p < 0.049). CONCLUSIONS:
      Appearance of severe hypokalemia is a frequent event among patients treated for
      BJIs with multiple antibiotic therapy, when this is prescribed in older age
      patients and associated with simultaneous use of diuretics. Due to possible
      increase in mortality risk in the short term, particular caution should be paid
      during intensive antibiotic treatment in these groups of patients.

PMID- 29018987
TI  - Seasonal dynamics of endoparasitic infections at an organic goat farm and the
      impact of detected infections on milk production.
AB  - This study evaluated patterns and species composition of parasitic infections
      detected over a 1-year period at an organic goat farm. As a result of
      coprological examination, the overall prevalence of observed strongylids (99%),
      coccidia of the genus Eimeria (98%), and Muellerius capillaris lungworms (93%)
      was calculated. The most prevalent strongylids recovered from incubated fecal
      samples were Haemonchus contortus (42%), genera Trichostrongylus (23%),
      Oesophagostomum columbianum (13%), and Teladorsagia circumcincta (11%). A maximum
      intensity of coccidia infection 5150 oocysts per gram, strongylids infection 9900
      eggs per gram and lungworm infection 867.26 larvae per gram were detected. The
      various effects (including environment, host, and parasites) on milk yield,
      lactose, protein, and fat were evaluated using generalized linear mixed models.
      Milk yield (P < 0.0001), milk fat (P < 0.01), and lactose (P < 0.0001) were
      affected by month, i.e., these parameters were influenced by the month of the
      year, regardless of the individual goat. With the intensity of infection detected
      in our study, only protein content was affected (P < 0.01) by parasitic infection
      (exclusively caused by strongylids). Correlation between measurements from one
      individual revealed that the goat itself can substantially decrease protein
      content but has much less of an effect on fat, milk yield, and lactose. Based on
      our results, we can conclude that a low intensity of parasitic infections does
      not significantly affect milk yield and the qualitative parameters of milk.

PMID- 29018989
TI  - Effects of prior aerobic exercise on sitting-induced vascular dysfunction in
      healthy men.
AB  - INTRODUCTION: Acute aerobic exercise prevents sitting-induced impairment of flow
      mediated dilation (FMD). Further, evidence suggests that sitting-induced
      impairment of FMD occurs via an oxidative stress-dependent mechanism that
      disrupts endothelial function. PURPOSE: We hypothesized that acute aerobic
      exercise would prevent impairment of femoral artery FMD by limiting oxidative
      stress responses that increase endothelin-1 (ET-1) levels and disrupt nitric
      oxide (NO) status. METHODS: In a randomized, cross-over study, healthy men (n =
      11; 21.2 +/- 1.9 years) completed two 3 h sitting trials that were preceded by 45
      min of either quiet rest (REST) or a single bout of continuous treadmill exercise
      (65% maximal oxygen consumption) (EX). Superficial femoral artery FMD, plasma
      glucose, malondialdehyde (MDA), ET-1, arginine (ARG) and its related metabolites
      [homoarginine (HA), asymmetric dimethylarginine (ADMA), symmetric
      dimethylarginine (SDMA)] were assessed at baseline, 1 h following EX (or REST) (0
      h), and at 1 h intervals during 3 h of uninterrupted sitting. Data were analyzed
      using repeated measures ANOVA. RESULTS: During REST, femoral artery FMD declined
      from baseline (2.6 +/- 1.8%) at 1, 2, and 3 h of sitting and resting shear rate
      decreased at 3 h. In contrast, when sitting was preceded by EX, femoral artery
      FMD (2.7 +/- 2.0%) and resting shear rate responses were unaffected. No between
      trial differences were detected for plasma glucose, MDA, ET-1, ARG, HA, ADMA, or
      SDMA. CONCLUSION: Prior aerobic exercise prevented the decline in femoral artery
      FMD that is otherwise induced by prolonged sitting independent of changes in
      oxidative stress, ET-1, and NO status.

PMID- 29018991
TI  - Ellagic acid glycosides with hepatoprotective activity from traditional Tibetan
      medicine Potentilla anserina.
AB  - Two new gallic acid glycosides, potentillanosides G (1) and H (2), were newly
      isolated from the methanol extract of the tuberous roots of Potentilla anserina
      (Rosaceae), together with a known compound, ellagic acid 3-O-alpha-L
      rhamnopyranoside (3). Their structures were elucidated on the basis of chemical
      and physicochemical evidence. Among the constituents, potentillanoside H (2, IC50
      = 99.5 MUM) was found to show hepatoprotective activity.

PMID- 29018992
TI  - Tenocyte proliferation and migration promoted by rat bone marrow mesenchymal stem
      cell-derived conditioned medium.
AB  - OBJECTIVES: To investigate the impact of secreted factors of rat bone marrow
      mesenchymal stem cells (MSCs) on the proliferation and migration of tenocytes and
      provide evidence for the development of MSC-based therapeutic methods of tendon
      injury. RESULTS: Rat bone marrow mesenchymal stem cell-derived conditioned medium
      (MSC-CM) promoted the proliferation of tenocytes within 24 h and decreased the
      percentage of tenocytes in G1 phase. MSC-CM activated the extracellular signal
      regulated kinase1/2 (ERK1/2) signal molecules, while the ERK1/2 inhibitor PD98059
      abrogated the MSC-CM-induced proliferation of tenocytes, decreased the fraction
      of tenocytes in the G1 phase and elevated p-ERK1/2 expression. Furthermore, MSC
      CM promoted the migration of tenocytes within 6 h, enhanced the formation of
      filamentous actin (F-actin) and increased the cellular and nuclear stiffness of
      tenocytes. CONCLUSIONS: MSC-CM promotes tenocyte proliferation by changing cell
      cycle distribution via the ERK1/2 signaling pathway. MSC-CM-induced tenocyte
      migration was accompanied by cytoskeletal polymerization and increases in
      cellular and nuclear stiffness.

PMID- 29018990
TI  - Safety and Effectiveness of an Endoscopically Placed Duodenal-Jejunal Bypass
      Device (EndoBarrier(r)): Outcomes in 114 Patients.
AB  - BACKGROUND: The duodenal-jejunal bypass liner (DJBL) is an endoscopically placed
      device designed to achieve weight loss and improve glycemic control in obese
      patients. Previous studies report promising results but typically included small
      patient numbers and short follow-up. This study aims to determine the safety and
      effectiveness of the device. METHODS: Study design: A series of all patients
      treated by the DJBL at our institutions. OUTCOME MEASUREMENTS: Weight loss,
      biochemical measures, complications. RESULTS: Between July 2012 and March 2015,
      114 consecutive patients were treated for a mean 51.1 weeks (standard deviation
      (SD) 19.9 weeks). Mean total body weight change from baseline was 12.0 kg (SD 8.5
      kg, p < 0.001). Mean percent total body weight loss (%TWL) was 10.5% (SD 7.3%).
      Mean HbA1c was not significantly improved, but of 10 patients on insulin, 4
      ceased insulin and 4 reduced insulin dosages. There was a significant decrease in
      hemoglobin and total cholesterol and a significant increase in serum alkaline
      phosphatase. Seventy-four percent of patients experienced at least one adverse
      event, some of them serious including 6 device obstructions, 5 gastrointestinal
      hemorrhages, 2 liver abscesses, and 1 acute pancreatitis. Seventy-four percent of
      patients experienced weight gain after removal with a mean 4.5 +/- 6.1 kg (p <
      0.0001) within the first 6 months after explantation. CONCLUSIONS: The DJBL
      provides significant but highly variable weight loss. Glycemic control was
      variable. Most insulin-requiring T2DM patients ceased or reduced insulin. Most
      patients experience an adverse event and most regain significant weight after
      device removal. Major adverse events can occur, including the potentially life
      threatening complications of hepatic abscess and gastrointestinal hemorrhage.

PMID- 29018988
TI  - Circulating chromogranin A and its fragments as diagnostic and prognostic disease
      markers.
AB  - Chromogranin A (CgA), a secretory protein released in the blood by neuroendocrine
      cells and neurons, is the precursor of various bioactive fragments involved in
      the regulation of the cardiovascular system, metabolism, innate immunity,
      angiogenesis, and tissue repair. After the original demonstration that
      circulating CgA can serve as a biomarker for a wide range of neuroendocrine
      tumors, several studies have shown that increased levels of CgA can be present
      also in the blood of patients with cardiovascular, gastrointestinal, and
      inflammatory diseases with, in certain cases, important diagnostic and prognostic
      implications. Considering the high structural and functional heterogeneity of the
      CgA system, comprising precursor and fragments, it is not surprising that the
      different immunoassays used in these studies led, in some cases, to discrepant
      results. Here, we review these notions and we discuss the importance of measuring
      total-CgA, full-length CgA, specific fragments, and their relative levels for a
      more thorough assessment of the pathophysiological function and
      diagnostic/prognostic value of the CgA system.

PMID- 29018993
TI  - Dopaminergic and non-dopaminergic gait components assessed by instrumented timed
      up and go test in Parkinson's disease.
AB  - The timed up and go test (TUG) is a widely used clinical test for the evaluation
      of balance and mobility. An instrumented version of TUG (iTUG) has been proposed
      to provide quantitative information on TUG performances. Here, we hypothesized
      that L-dopa may differently influence gait parameters recorded by a portable
      inertial sensor. To test this idea, we evaluated iTUG test in patients with
      Parkinson's disease (PD), both in L-dopa OFF and ON state. Twenty-eight PD
      patients performed the iTUG. Subjects were instructed to perform the task both in
      practical "OFF" and "ON" state. The system differentiated the test in six phases,
      recording phase durations, three-axial accelerations, average and peak angular
      speeds during turning. In all patients, sit-to-stand vertical and medio-lateral
      accelerations together with turning phase duration and angular speeds improved
      after L-dopa administration, while sit-to-stand and stand-to-sit phases antero
      posterior accelerations were less responsive. In PD, L-dopa modulates iTUG in
      different ways, mostly improving the turning phases and less acting on postural
      controls during the sit-to-stand and stand-to-sit phases. Our results suggest
      different involvement of dopaminergic mechanisms on gait as assessed by iTUG.
      This is important for those aspects which are not improved by pharmacological
      therapy.

PMID- 29018994
TI  - Proper land use for heavy metal-polluted soil based on enzyme activity analysis
      around a Pb-Zn mine in Feng County, China.
AB  - Enzymes in the soil are useful for assessing heavy metal soil pollution. We
      analyzed the activity of a number of enzymes, including urease, protease,
      catalase, and alkaline phosphatase, in three types of land (farmland, woodland,
      and grassland) to evaluate soil pollution by heavy metals (Pb, Zn, and Cd). Our
      results showed that the tested soil was polluted by a combination of Pb, Zn, and
      Cd, but the primary pollutant was Cd. An ecological dose analysis demonstrated
      that urease was the most sensitive enzyme to Pb and Cd in the farmland, and
      catalase and phosphatase were the most sensitive enzymes to Pb, Zn, and Cd in the
      woodland and grassland. The ecological risk of Cd (E Cd ) was the smallest in all
      three types of land, suggesting that Cd was the major metal inhibiting enzyme
      activity. Electrical conductivity (EC) was shown to be a negative regulator,
      while nitrogen, phosphorus, and clay contents were positive regulators of soil
      enzyme activity. The total enzyme index (TEI) inhibition rates in the woodland
      were 22.2 and 38.6% under moderate and heavy pollution, respectively, which were
      lower than those of the other two types of land. Therefore, woodlands might be
      the optimum land use choice in relieving heavy metal pollution. Taken together,
      this study identified the key metal pollutant inhibiting soil enzyme activity and
      suitable land use patterns around typical metal mine. These results provide
      possible improvement strategies to the phytomanagement of metal-contaminated land
      around world.

PMID- 29018995
TI  - Impulsivity and Response Latency in Non-Suicidal Self-Injury: The Role of
      Negative Urgency in Emotion Regulation.
AB  - Impulsivity is thought to be a contributing factor in non-suicidal self-injury
      (NSSI), yet the research is limited and inconsistent. In particular, little is
      known about how impulsivity is associated with response latency between initial
      urge and later self-injury, emotion regulation processes, or severity of NSSI. In
      this study, we tested group differences between participants with and without a
      history of NSSI on a questionnaire measure of impulsivity. In addition, we tested
      hypothesized correlations between impulsivity and relevant variables within the
      NSSI sample using questionnaires and self-reported response latency between urge
      and injury. Participants included 159 undergraduate students, 84 with an NSSI
      history and 75 without an NSSI history. Results indicated greater impulsivity on
      facets of Urgency and (lack of) Perseverance for the NSSI group. Within the NSSI
      sample, facets of impulsivity were associated with difficulties in emotion
      regulation and NSSI severity, but not response latency. In addition, response
      latency, a possible behavioral marker of impulsivity, was not associated with
      emotion regulation processes or NSSI frequency. These results suggest that higher
      scores on self-report measures of impulsivity, but not behavioral response
      latency measures, are associated with emotion regulation processes in individuals
      who self-injure.

PMID- 29018997
TI  - Gastrointestinal perforation related to lenvatinib, an anti-angiogenic inhibitor
      that targets multiple receptor tyrosine kinases, in a patient with metastatic
      thyroid cancer.
AB  - Lenvatinib, a novel potent multikinase inhibitor, was approved for the treatment
      of radioiodine-refractory differentiated thyroid cancer based on results from
      phase III trial (SELECT study). Thyroid cancer is a diverse disease that includes
      anaplastic thyroid cancer (ATC), which the most aggressive form of the disease,
      although it accounts for <2% of all thyroid cancers. Current treatments for ATC
      have limited efficacy. We report the case of a woman with recurrent well
      differentiated papillary carcinoma of the thyroid that had transformed into ATC
      who developed a perforation of the small intestine secondary to a marked effect
      of lenvatinib. She received lenvatinib (24 mg once a day) at only two doses
      during two weeks due to pleurodesis with talc for malignant pleural effusion.
      Eventually, she developed peritonitis due to the perforation and died of sepsis.
      However, an autopsy revealed marked efficacy of lenvatinib for ATC at a
      metastatic site in the small intestine despite limited exposure to the drug.
      Here, we report on our experience with lenvatinib treatment and gastrointestinal
      perforation concerning anti-angiogenic therapy.

PMID- 29018998
TI  - Nano-scale simulation based study of creep behavior of bimodal nanocrystalline
      face centered cubic metal.
AB  - In this paper, the creep behavior of nanocrystalline Ni having bimodal grain
      structure is investigated using molecular dynamics simulation. Analysis of
      structural evolution during the creep process has also been performed. It is
      observed that an increase in size of coarse grain causes improvement in creep
      properties of bimodal nanocrystalline Ni. Influence of bimodality (i.e., size
      difference between coarse and fine grains) on creep properties are found to be
      reduced with increasing creep temperature. The dislocation density is observed to
      decrease exponentially with progress of creep deformation. Grain boundary
      diffusion controlled creep mechanism is found to be dominant at the primary creep
      region and the initial part of the secondary creep region. After that shear
      diffusion transformation mechanism is found to be significantly responsible for
      deformation as bimodal nanocrystalline Ni transforms to amorphous structure with
      further progress of the creep process. The presence of <0, 2, 8, 5>, <0, 2, 8, 2
      >, and <0, 1, 10, 2 > distorted icosahedra has a significant influence on creep
      rate in the tertiary creep regime according to Voronoi cluster analysis.

PMID- 29018996
TI  - Water availability and environmental temperature correlate with geographic
      variation in water balance in common lizards.
AB  - Water conservation strategies are well documented in species living in water
      limited environments, but physiological adaptations to water availability in
      temperate climate environments are still relatively overlooked. Yet, temperate
      species are facing more frequent and intense droughts as a result of climate
      change. Here, we examined variation in field hydration state (plasma osmolality)
      and standardized evaporative water loss rate (SEWL) of adult male and pregnant
      female common lizards (Zootoca vivipara) from 13 natural populations with
      contrasting air temperature, air humidity, and access to water. We found
      different patterns of geographic variation between sexes. Overall, males were
      more dehydrated (i.e. higher osmolality) than pregnant females, which likely
      comes from differences in field behaviour and water intake since the rate of SEWL
      was similar between sexes. Plasma osmolality and SEWL rate were positively
      correlated with environmental temperature in males, while plasma osmolality in
      pregnant females did not correlate with environmental conditions, reproductive
      stage or reproductive effort. The SEWL rate was significantly lower in
      populations without access to free standing water, suggesting that lizards can
      adapt or adjust physiology to cope with habitat dryness. Environmental humidity
      did not explain variation in water balance. We suggest that geographic variation
      in water balance physiology and behaviour should be taken account to better
      understand species range limits and sensitivity to climate change.

PMID- 29019000
TI  - Does Caesarean Section Affect Breastfeeding Practices in China? A Systematic
      Review and Meta-Analysis.
AB  - Objectives To ascertain the association between caesarean delivery and
      breastfeeding practices in China. Methods We conducted a systematic review and
      meta-analysis following the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology
      (MOOSE) guidelines. Electronic databases of CNKI, Medline, EMBASE, CINAHL,
      ProQuest and Science Direct were searched and screened to identify relevant
      articles from January 1990 to June 2015. Both fixed and random effect meta
      analysis techniques were used to estimate the pooled effect size between
      caesarean delivery and breastfeeding outcomes at different time points.
      Sensitivity analysis and publication bias test were also conducted. Results Forty
      six studies were eligible for the qualitative synthesis of systematic review;
      among them, 27 studies were included for the meta-analysis. At the early
      postpartum period, the odds of exclusive breastfeeding after caesarean section
      was 47% (pooled OR 0.53, 95% CI 0.41, 0.68) lower than that after vaginal
      delivery. At 4 months postpartum, the odds of breastfeeding was similarly lower
      (pooled OR 0.61, 95% CI 0.53, 0.71) for caesarean mothers. Substantial
      heterogeneity among studies was detected for both breastfeeding outcomes.
      Subgroup analyses stratified by study design, time points of breastfeeding
      outcomes and definitions of breastfeeding all confirmed the negative association
      between caesarean section and breastfeeding prevalence. Conclusions In China,
      breastfeeding practices were affected adversely by caesarean delivery. Therefore,
      health policy to improve breastfeeding outcomes should take this into
      consideration.

PMID- 29018999
TI  - Population pharmacokinetics of gabapentin in healthy Korean subjects with
      influence of genetic polymorphisms of ABCB1.
AB  - The objective of this study was to perform population pharmacokinetic (PK)
      analysis of gabapentin in healthy Korean subjects and to investigate the possible
      effect of genetic polymorphisms (1236C > T, 2677G > T/A, and 3435C > T) of ABCB1
      gene on PK parameters of gabapentin. Data were collected from bioequivalence
      studies, in which 173 subjects orally received three different doses of
      gabapentin (300, 400, and 800 mg). Only data from reference formulation were
      used. Population pharmacokinetics (PKs) of gabapentin was estimated using a
      nonlinear mixed-effects model (NONMEM). Gabapentin showed considerable inter
      individual variability (from 5.2- to 8.7-fold) in PK parameters. Serum
      concentration of gabapentin was well fitted by a one-compartment model with first
      order absorption and lag time. An inhibitory Emax model was applied to describe
      the effect of dose on bioavailability. The oral clearance was estimated to be
      11.1 L/h. The volume of distribution was characterized as 81.0 L. The absorption
      rate constant was estimated at 0.860 h-1, and the lag time was predicted at 0.311
      h. Oral bioavailability was estimated to be 68.8% at dose of 300 mg, 62.7% at
      dose of 400 mg, and 47.1% at dose of 800 mg. The creatinine clearance
      significantly influenced on the oral clearance (P < 0.005) and ABCB1 2677G > T/A
      genotypes significantly influenced on the absorption rate constant (P < 0.05) of
      gabapentin. However, ABCB1 1236C > T and 3435C > T genotypes showed no
      significant effect on gabapentin PK parameters. The results of the present study
      indicate that the oral bioavailability of gabapentin is decreased when its dosage
      is increased. In addition, ABCB1 2677G > T/A polymorphism can explain the
      substantial inter-individual variability in the absorption of gabapentin.

PMID- 29019001
TI  - Anaplastic thyroid cancer and hyperfractionated accelerated radiotherapy (HART)
      with and without surgery.
AB  - Anaplastic carcinoma of the thyroid gland (ATC) is one of the most aggressive
      cancers in humans. With insufficient treatment, the disease most often leads to
      death in suffocation. From 2002, our treatment strategy has been
      hyperfractionated accelerated radiotherapy (HART) with high doses (64 Gy) to the
      neck, followed by surgery 4-8 weeks later if feasible, with the aim to gain
      control in the neck. After a pathology review, 51 patients were diagnosed with
      ATC in the period 2002-2014 in the south-east of Norway. Thirty-one received
      HART, and we present a study of these patients, with death in suffocation as the
      primary endpoint and survival as the second. No patients treated with HART died
      in suffocation. Six had a tracheostomy during their course of disease, of whom
      four were dependent on a tracheal cannula when they died. The best median
      survival, 19 months, was obtained in the 13 patients where both radiotherapy and
      surgery were possible as primary treatments. Only surgery came out as a
      prognostic factor for survival in multivariate analysis. Patients surviving more
      than 2 years were characterised by having surgery with R0 resection and no or
      small residual foci of ATC in the specimens. Stage 4C patients survived 3 months
      only.

PMID- 29019002
TI  - A meta-analysis of clinical electro-oculography values.
AB  - BACKGROUND: The aim of the meta-analysis was to derive a range of mean normal
      clinical electrooculogram (EOG) values from a systematic review of published EOG
      studies that followed the guidelines of the ISCEV standard for clinical electro
      oculography. METHODS: A systematic literature review was performed using four
      relevant databases limited to peer-reviewed articles in English between 1967 and
      February 2017. Studies reporting clinical EOG or FO normal values were included
      when the report used a standard 30 degrees  horizontal saccade, a retinal
      luminance of between 100 and 250 cd m-2, and had > 10 subjects in their normative
      values. The search identified 1145 articles after duplicates were removed with
      subsequent screening of the abstracts excluding a further 1098, resulting in 47
      full-text articles that were then assessed by the author (PC) with a final nine
      articles meeting the inclusion criteria. An overall effect estimate using inverse
      variance-weighted meta-analysis was performed to estimate the mean values for the
      light peak/dark trough ratio (LP:DT ratio) (dilated and undilated), the time to
      the LP, the amplitude of the LP, dark trough (DT) and the fast oscillation (FO)
      peak-to-trough ratio from the included studies. RESULTS: The mean dilated LP:DT
      ratio was 2.35 (95% CI 2.28-2.42); undilated LP:DT ratio was 2.37 (95% CI 2.28
      2.45); LP amplitude was 835 (95% CI 631-1039) uV and the mean time to the LP
      being 8.2 (95% CI 7.7-8.7) min. The mean DT amplitude was 358 (95% CI 292-424)
      uV, and the mean FO peak-to-trough ratio was 1.13 (95% CI 1.11-1.16). The results
      of the LP/DT ratio are drawn from studies with a mean +/- standard deviation (SD)
      age of 34.08 +/- 12.93 years for dilated and 33.65 +/- 12.28 years for undilated
      LP/DT ratios. CONCLUSIONS: The meta-analysis of EOG studies has generated a
      reference range of normal mean values for clinicians to refer to when using the
      ISCEV clinical EOG. It provides a potential method to generate similar data sets
      from published normal values in related visual electrophysiology tests.

PMID- 29019003
TI  - Role of Dynein Axonemal Heavy Chain 6 Gene Expression as a Possible Biomarker for
      Huntington's Disease: a Translational Study.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      characterized by motor dysfunction, cognitive deficits, and psychiatric symptoms.
      The primary genetic cause is an expansion of cytosine adenine guanine (CAG)
      nucleotides of the huntingtin gene, which codes an important protein involved
      with neuronal signaling. The severity of HD correlates with the number of CAG
      repeats and individuals with longer expansions have an earlier onset and more
      severe symptoms. A microarray study conducted by our research group showed
      alteration in DNAH6 gene (encoding dynein axonemal heavy chain 6). DNAH6 belongs
      to dynein family, whose members are constituents of the microtubule-associated
      motor proteins and is downregulated in the striatum of a HD mouse model (knockin
      HdhQ111/Q111). In this manner, our goal was to confirm these downregulations in
      the mouse model and verify if the same alteration in the axonemal DNAH6 gene
      expression is observed in blood samples of HD patients. Blood samples were
      collected from 17 patients with clinical diagnosis of HD and 12 healthy
      individuals and RNA extracted for qPCR analysis. Microarray data were confirmed
      by qPCR in knockin HdhQ111/Q111, and DNAH6 was severely decreased in those mice,
      as compared to control mice (HdhQ20/Q20). Notably, decreased expression of DNAH6
      gene was also observed in HD patients when compared to control group and
      negatively correlates with the CAG expansion. Although further studies are
      necessary to underlie the molecular mechanisms of dynein-htt interaction, this
      data highlights DNAH6 as a potential new blood marker for HD.

PMID- 29019004
TI  - Multiple sclerosis spatial cluster in Tuscany.
AB  - Tuscany (Central Italy) is a high-risk area for multiple sclerosis (MS) with a
      prevalence of 188 cases per 100,000 at 2011, and it is characterized by a
      heterogeneous geographic distribution of this disease. Our objective was to
      update prevalence at 2013 and to evaluate the presence of spatial clusters in
      Tuscany. The MS prevalence was evaluated on 31 December 2013 using a validated
      case-finding algorithm, based on administrative data. To identify spatial
      clusters, we calculated standardized morbidity ratios (SMRs) for each Tuscan
      administrative municipality. In addition to the classical approach, we applied
      the hierarchical Bayesian model to overcome random variability due to the
      presence of small number of cases per municipality. We identified 7330 MS
      patients (2251 males and 5079 females) with an overall prevalence of
      195.4/100,000. The SMR for each Tuscan municipality ranged from 0 to 271.4, but
      this approach produced an extremely non-homogeneous map. On the contrary, the
      Bayesian map was much smoother than the classical one. The posterior probability
      (PP) map showed prevalence clusters in some areas in the province of Massa
      Carrara, Pistoia, and Arezzo, and in the municipalities of Siena, Florence, and
      Barberino Val d'Elsa. Our prevalence data confirmed that Tuscany is a high-risk
      area, and we observed an increasing trend during the time. Using the Bayesian
      method, we estimated area-specific prevalence in each municipality reducing the
      random variation and the effect of extreme prevalence values in small areas that
      affected the classical approach.

PMID- 29019005
TI  - When theory meets experiment: the PD-1 challenge.
AB  - Applying atomistic computational modeling to drug discovery has proven to be a
      hugely successful approach, allowing drug-receptor interactions to be predicted
      and drugs to be optimized for potency, selectivity, and safety. However, when it
      comes to predicting protein-protein interactions and to rationally designing
      regulators of these interactions, computational tools often fail. Here, we report
      one of the rare instances where state-of-the-art computer simulations, guided by
      experiment, were able to correctly predict one of the most sophisticated protein
      protein interactions. We revisit our previous discovery of the complex of human
      PD-1 with the ligand PD-L1 and compare our earlier findings with the recently
      published crystal structure of the same complex. Side-by-side comparison of the
      model of the complex with its crystal structure reveals outstanding agreement and
      suggests that our protein-protein prediction workflow could be applied to similar
      problems.

PMID- 29019006
TI  - Ventilation inhomogeneity in obstructive lung diseases measured by electrical
      impedance tomography: a simulation study.
AB  - Electrical impedance tomography (EIT) has mostly been used in the Intensive Care
      Unit (ICU) to monitor ventilation distribution but is also promising for the
      diagnosis in spontaneously breathing patients with obstructive lung diseases.
      Beside tomographic images, several numerical measures have been proposed to
      quantitatively assess the lung state. In this study two common measures, the
      'Global Inhomogeneity Index' and the 'Coefficient of Variation' were compared
      regarding their capability to reflect the severity of lung obstruction. A three
      dimensional simulation model was used to simulate obstructed lungs, whereby
      images were reconstructed on a two-dimensional domain. Simulations revealed that
      minor obstructions are not adequately recognized in the reconstructed images and
      that obstruction above and below the electrode plane may result in misleading
      values of inhomogeneity measures. EIT measurements on several electrode planes
      are necessary to apply these measures in patients with obstructive lung diseases
      in a promising manner.

PMID- 29019008
TI  - Retained Foreign Body After Adjustable Gastric Band Removal: a Case Series.
AB  - Laparoscopic adjustable gastric band (LAGB) has weight loss and associated
      obesity-related disease benefits. Well-recognised LABG complications lead to a
      higher re-operation rate when compared to other obesity surgeries and therefore
      potential for retained foreign body. By way of a case series, we have evaluated
      retained foreign body after the intended complete removal of a gastric band.
      Analysis focused on circumstances and similarities leading to retained foreign
      body. From the series, the most commonly retained band component is band tubing.
      Difficult surgery or surgery associated with intra-operative complications may
      lead to increased chances of retained gastric band. Strategies to prevent this
      complication should be implemented. Specifically, removal technique, equipment
      familiarisation and post removal inspection all play a role.

PMID- 29019009
TI  - Electroinduced Extraction of Human Ferritin Heavy Chain Expressed in Hansenula
      polymorpha.
AB  - A protocol for the efficient and selective recovery of human ferritin heavy chain
      (FTH1) expressed intracellularly in Hansenula polymorpha was developed. It was
      based on electropermeabilisation and an increase in the cell wall porosity by
      pulsed electric field (PEF) treatment and subsequent incubation with a low
      concentration of a lytic enzyme. Irreversible plasma membrane permeabilisation
      was induced by applying rectangular electric pulses in the flow mode. The
      electrical treatment itself did not cause the release of the recombinant protein
      but induced the sensitisation of H. polymorpha cells to the lytic enzyme.
      Consequently, the subsequent incubation of the permeabilised cells with lyticase
      led to the recovery of approximately 90% of the recombinant protein, with a
      purification factor of 1.8. A similar efficiency was obtained by using the
      industrial lytic enzyme Glucanex. The released FTH1 appears in the form of an
      oligomer with a molecular mass of approximately 480 kDa, which is able to bind
      iron. The possibility for scaling the proposed protocol is discussed.

PMID- 29019007
TI  - Evaluation on exposures to particulate matter at a junior secondary school: a
      comprehensive study on health risks and effective inflammatory responses in
      Northwestern China.
AB  - Air pollutant measurement and respiratory inflammatory tests were conducted at a
      junior secondary school in Xi'an, Northwestern China. Hazardous substances
      including particulate matters (PMs), black carbon (BC) and particle-bounded
      polycyclic aromatic hydrocarbons (PAHs) were quantified both indoors and outdoors
      of the school. Source characterization with organic tracers and particle-size
      distribution demonstrated that the school's air was mostly polluted by combustion
      emissions from the surrounding environment. The evaluation of health assessment
      related to air quality was conducted by two methods, including potential risk
      estimation of air pollutants and direct respiratory inflammatory test. The
      incremental lifetime cancer risks associated with PAHs were estimated and were
      1.62 * 10-6 and 2.34 * 10-6, respectively, for indoor and outdoor fine PMs. Both
      the values exceeded the threshold value of 1 * 10-6, demonstrating that the
      carcinogenic PAHs are a health threat to the students. Respiratory inflammatory
      responses of 50 students who studied in the sample classroom were examined with a
      fractional exhaled nitric oxide (FeNO) test, with the aid of health
      questionnaires. The average FeNO concentration was 17.4 +/- 8.5 ppb, which was
      slightly lower than the recommended level of 20 ppb established by the American
      Thoracic Society for children. However, a wide distribution and 6% of the values
      were > 35 ppb, suggesting that the potentials were still high for eosinophilic
      inflammation and responsiveness to corticosteroids. A preliminary interpretation
      of the relationship between air toxins and respiratory inflammatory response
      demonstrated the high exposure cancer risks and inflammatory responses of the
      students to PMs in the city.

PMID- 29019010
TI  - Effect of the Presence of Surfactants and Immobilization Conditions on Catalysts'
      Properties of Rhizomucor miehei Lipase onto Chitosan.
AB  - Lipase from Rhizomucor miehei (RML) was immobilized onto chitosan support in the
      presence of some surfactants added at low levels using two different strategies.
      In the first approach, the enzyme was immobilized in the presence of surfactants
      on chitosan supports previously functionalized with glutaraldehyde. In the second
      one, after prior enzyme adsorption on chitosan beads in the presence of
      surfactants, the complex chitosan beads-enzyme was then cross-linked with
      glutaraldehyde. The effects of surfactant concentrations on the activities of
      free and immobilized RML were evaluated. Hexadecyltrimethylammonium bromide
      (CTAB) promoted an inhibition of enzyme activity while the nonionic surfactant
      Triton X-100 caused a slight increase in the catalytic activity of the free
      enzyme and the derivatives produced in both methods of immobilization. The best
      derivatives were achieved when the lipase was firstly adsorbed on chitosan beads
      at 4  degrees C for 1 h, 220 rpm followed by cross-link the complex chitosan
      beads-enzyme with glutaraldehyde 0.6% v.v-1 at pH 7. The derivatives obtained
      under these conditions showed high catalytic activity and excellent thermal
      stability at 60 degrees  and 37  degrees C. The best derivative was also
      evaluated in the synthesis of two flavor esters namely methyl and ethyl butyrate.
      At non-optimized conditions, the maximum conversion yield for methyl butyrate was
      89%, and for ethyl butyrate, the esterification yield was 92%. The results for
      both esterifications were similar to those obtained when the commercial enzyme
      Lipozyme(r) and free enzyme were used in the same reaction conditions and higher
      than the one achieved in the absence of the selected surfactant.

PMID- 29019011
TI  - A systematic review and meta-analysis of mechanical vs biological composite
      aortic root replacement, early and 1-year results.
AB  - OBJECTIVE: Composite aortic root replacement is a standard procedure for various
      aortic root pathologies. This systematic review was set to identify the
      postoperative outcomes for composite mechanical root replacement (mCRR) compared
      to composite biological root replacement (bCRR). METHODS: We systematically
      reviewed four major databases for all papers assessing outcomes in composite root
      replacement. Articles selected were chosen by two reviewers. Amongst our
      inclusion and exclusion criteria, all pediatric populations were excluded as were
      studies with a cohort less than 50 patients. RESULTS: We identified seven studies
      that conformed to our inclusion criteria and incorporated 2240 patients. In
      hospital mortality was higher but non-significant in the mechanical group (6.1 vs
      4.2% respectively). There was no significant difference demonstrated in the risk
      of in-hospital stroke, late stroke and re-operation in either groups.
      Additionally, there was no significant difference in: endocarditis, 1-year
      mortality, 5-year mortality, mean cardiopulmonary or aortic cross-clamp time.
      CONCLUSIONS: Composite mechanical root offers no superiority to composite
      biological root. There is a significant increase in the perioperative bleeding
      amongst composite mechanical root cohort. There is a need for further randomized
      control trail to assess the efficacy of either methods.

PMID- 29019012
TI  - Process Evaluation of the BOOST-ATM Transition Planning Program for Adolescents
      on the Autism Spectrum: A Strengths-Based Approach.
AB  - A process evaluation was conducted to determine the effectiveness, usability, and
      barriers and facilitators related to the Better OutcOmes & Successful Transitions
      for Autism (BOOST-ATM), an online transition planning program. Adolescents on the
      autism spectrum (n = 33) and their parents (n = 39) provided feedback via an
      online questionnaire. Of these, 13 participants were interviewed to gain in-depth
      information about their experiences. Data were analyzed using descriptive
      statistics and thematic analysis. Four themes were identified: (i) taking action
      to overcome inertia, (ii) new insights that led to clear plans for the future,
      (iii) adolescent empowerment through strengths focus, and (iv) having a champion
      to guide the way. The process evaluation revealed why BOOST-ATM was beneficial to
      some participants more than others. Trial registration #ACTRN12615000119594.

PMID- 29019013
TI  - Larkinella terrae sp. nov., isolated from soil on Jeju Island, South Korea.
AB  - A Gram-stain negative, non-motile, rod-shaped, aerobic bacterium, designated 15J8
      8T, was isolated from a soil sample collected on Jeju Island, South Korea, and
      characterized taxonomically using a polyphasic approach. Comparative 16S rRNA
      gene sequence analysis showed that strain 15J8-8T belongs to the family
      Cytophagaceae and is related to Larkinella bovis M2TB15T (95.0%), 'Larkinella
      harenae' 15J9-9 (94.5%), Larkinella arboricola Z0532T (93.2%), and Larkinella
      insperata LMG 22510T (93.0%). The DNA G+C content of strain 15J8-8T was 50.5
      mol%. The detection of phosphatidylethanolamine and two unidentified polar lipids
      as major polar lipids; menaquinone-7 as the predominant quinone; and C16:1
      omega5c, C16:0 N alcohol, and iso-C15:0 as the major fatty acids also supported
      the affiliation of the isolate to the genus Larkinella. Based on its phenotypic
      properties and phylogenetic distinctiveness, strain 15J8-8T should be classified
      in the genus Larkinella as representative of a novel species, for which the name
      Larkinella terrae sp. nov. is proposed. The type strain is 15J8-8T (= KCTC 52001T
      = JCM 31990T).

PMID- 29019014
TI  - Incontinence in autism spectrum disorder: a systematic review.
AB  - Autism spectrum disorders (ASD) are defined by persistent deficits in reciprocal
      social interaction, communication, and language, as well as stereotyped and
      repetitive behavior. Functional incontinence, as well as ASD are common disorders
      in childhood. The aim of this systematic review was to give an overview of the co
      occurrence of nocturnal enuresis (NE), daytime urinary incontinence (DUI), and
      fecal incontinence (FI) in ASD, and vice versa, of ASD in children with
      incontinence. A systematic literature search of the terms "incontinence",
      "enuresis", and "encopresis" in combination with "autism" or "Asperger" in four
      databases (Scopus, PubMed, PsycInfo and Web of science) was conducted. All
      studies that examined incontinence frequencies in samples with ASD, and studies
      that measured frequencies of ASD diagnoses or symptoms in samples with
      incontinence were included. Risk of bias and limitations of each study were
      described. After eligibility assessment, 33 publications were included in the
      review. The published literature implies a higher prevalence of incontinence in
      children with ASD compared to typically developing children. Limitations and
      biases as inappropriate diagnostic criteria for ASD and incontinence, selected
      samples, or lack of control groups are reported. Associations of incontinence in
      ASD with psychopathological symptoms were found. Vice versa, ASD symptoms are
      found in incontinent children, but no study included a non-ASD control sample.
      Incontinence symptoms are also reported as an adverse effect of medication in
      ASD. Due to methodological problems and definitional discrepancies in some
      publications, results have to be interpreted cautiously. Research in ASD and
      incontinence is scarce. More systematic research including state-of-the-art
      assessments is needed.

PMID- 29019015
TI  - Conformations of a charged vesicle interacting with an oppositely charged
      particle.
AB  - Endocytotic and exocytotic processes are usually studied using particle-vesicle
      systems in theory, but most of them are electroneutral. Nevertheless, charged
      particle-vesicle systems are much closer to real biological systems. Therefore,
      wrapping behaviors of a negatively charged vesicle wrapping a positively charged
      particle are systematically investigated by a series of 2D dynamical simulations
      in this article. The competition between the elastic bending energy and the
      electrostatic energy dictates the vesicle configuration and charge distribution.
      It is found that only for intermediate charge concentrations and small particle
      sizes a vesicle can completely engulf the particle. When the charge density is
      high, the interaction between vesicle and particle is unexpectedly weakened by
      both the hardening effect of the charged membrane and the effective
      transportation-frozen effect of the charged components. When the particle is
      strongly charged, multi-layer folding conformations are observed. These studies
      may provide important insights into mechanism of endocytotic and exocytotic
      processes in biological systems.

PMID- 29019017
TI  - Leptospirosis-associated catastrophic respiratory failure supported by
      extracorporeal membrane oxygenation.
AB  - A previously healthy, 39-year-old obese farmer, arrived hypotensive and
      tachycardic, with fever, myalgia, headache, abdominal pain, diarrhea, and
      progressive dyspnea. Ten days before symptoms onset, he was in direct contact
      with mice and working in a contaminated drain. Patient laboratory showed acute
      kidney injury and thrombocytopenia. Chest X-ray exhibited bilateral diffuse
      interstitial infiltrates. First-line empirical antibiotics were started and
      influenza discarded. Patient evolved with severe respiratory failure, associated
      with hemoptysis, and rapidly severe hemodynamic compromise. Despite neuromuscular
      blockade and prone positioning, respiratory failure increased. Accordingly, veno
      venous ECMO was initiated, with bilateral femoral extraction and jugular return.
      After ECMO connection, there was no significant improvement in oxygenation, and
      low pre-membrane saturations and low arterial PaO2 of the membrane showed that we
      were out of the limits of the rated flow. Thus, a second membrane oxygenator was
      installed in parallel. Afterward, oxygenation improved, with subsequent perfusion
      enhancement. Regarding etiology, due to high suspicion index, Leptospira serology
      was performed, coming back positive and meropenem was maintained. The patient
      ultimately recovered and experience excellent outcome. The clinical relevance of
      the case is the scared evidence of leptospirosis-associated severe respiratory
      failure treated with ECMO. This experience emphasizes the importance of an
      optimal support, which requires enough membrane surface and flow for an obese,
      highly hyperdynamic patient, during this reversible disease. A high index of
      suspicion is needed for an adequate diagnosis of leptospirosis to implement the
      correct treatment, particularly in the association of respiratory failure,
      pulmonary hemorrhage, and an epidemiological-related context.

PMID- 29019016
TI  - Repurposing Zidovudine in combination with Tigecycline for treating carbapenem
      resistant Enterobacteriaceae infections.
AB  - The global emergence of carbapenem-resistant Enterobacteriaceae (CRE) presents a
      significant clinical concern, prompting the WHO to prioritize CRE as a top
      priority pathogen in their 2017 global antibiotic-resistant bacteria priority
      list. Due to the fast-depleting antibiotic arsenal, clinicians are now resorting
      to using once-abandoned, highly toxic antibiotics such as the polymyxins and
      aminoglycosides, creating an urgent need for new antibiotics. Drug repurposing,
      the application of an approved drug for a new therapeutic indication, is deemed a
      plausible solution to this problem. A total of 1,163 FDA-approved drugs were
      screened for activity against a clinical carbapenem- and multidrug-resistant E.
      coli isolate using a single-point 10 MUM assay. Hit compounds were then assessed
      for their suitability for repurposing. The lead candidate was then tested against
      a panel of clinical CREs, a bactericidal/static determination assay, a time-kill
      assay and a checkerboard assay to evaluate its suitability for use in combination
      with Tigecycline against CRE infections. Three drugs were identified. The lead
      candidate was determined to be Zidovudine (azidothymidine/AZT), an oral anti
      viral drug used for HIV treatment. Zidovudine was shown to be the most promising
      candidate for use in combination with Tigecycline to treat systemic CRE
      infections. Further experiments should involve the use of animal infection
      models.

PMID- 29019018
TI  - Long-term anabolic steroids in male bodybuilders induce cardiovascular structural
      and autonomic abnormalities.
AB  - OBJECTIVE: The aims of this study were to examine the hypothesis that users of
      anabolic androgenic steroids (AAS) would have cardiac autonomic disorders and
      that there is a correlation between sympathetic modulation, high blood pressure
      (BP) and alterations to cardiac dimensions. METHODS: Forty-five male subjects
      were enrolled in the study. They were categorized into three groups comprising
      bodybuilders actively using AAS (AAS users; n = 15), bodybuilders who had never
      used AAS (nonusers; n = 15) and age-paired healthy sedentary controls (n = 15).
      Hemodynamic parameters, linear and nonlinear analyses of heart rate variability
      and electrocardiography and echocardiography analyses were performed at rest.
      RESULTS: Bodybuilders in the AAS group had a higher mean BP than those in the ASS
      nonuser group (p < 0.05) and the sedentary controls (p < 0.001). Cardiac
      sympathetic modulation was higher in AAS users than in AAS nonusers (p < 0.05)
      and the sedentary controls (p < 0.001), and parasympathetic modulation was lower
      in AAS users than in nonusers and the sedentary controls (p < 0.05). Shannon
      entropy was lower in AAS users than in the sedentary (p < 0.05) controls, and the
      corrected QT interval and QT dispersion were higher in AAS users than in the
      sedentary controls (p < 0.05). The interventricular septal thickness, left
      ventricle posterior wall thickness and relative diastolic wall thickness were
      higher in AAS users than in AAS nonusers and the sedentary controls (p < 0.001).
      AAS users showed a positive correlation between increased sympathetic modulation
      and high BP (r = 0.48, p < 0.005), as well as sympathetic modulation and cardiac
      hypertrophy (r = 0.66, p < 0.001). CONCLUSION: There was a marked cardiac
      autonomic alteration in AAS users, with a shift toward sympathetic modulation
      predominance and vagal attenuation. The high BP observed in our group of
      bodybuilders using AAS was associated with increased sympathetic modulation, and
      this increased sympathetic modulation was associated with structural alterations
      in the heart. This association may constitute an important mechanism linking AAS
      abuse to increased cardiovascular risk.

PMID- 29019019
TI  - Healthy Grandparenthood: How Long Is It, and How Has It Changed?
AB  - Healthy grandparenthood represents the period of overlap during which
      grandparents and grandchildren can build relationships, and grandparents can make
      intergenerational transfers to younger kin. The health of grandparents has
      important implications for upward and downward intergenerational transfers within
      kinship networks in aging societies. Although the length of grandparenthood is
      determined by fertility and mortality patterns, the amount of time spent as a
      healthy grandparent is also affected by morbidity. In this study, we estimate the
      length of healthy grandparenthood for the first time. Using U.S. and Canadian
      data, we examine changes in the length of healthy grandparenthood during years
      when grandparenthood was postponed, health improved, and mortality declined. We
      also examine variation in healthy grandparenthood by education and race/ethnicity
      within the United States. Our findings show that the period of healthy
      grandparenthood is becoming longer because of improvements in health and
      mortality, which more than offset delays in grandparenthood. Important variation
      exists within the United States by race/ethnicity and education, which has
      important implications for family relationships and transfers.

PMID- 29019022
TI  - Distribution of lacosamide in the rat brain assessed by in vitro slice technique.
AB  - Lacosamide is a newer anticonvulsant and is the only one that enhances the slow
      inactivation of voltage gated sodium channels. It is also claimed to have disease
      modifying potential, but its pharmacokinetic properties have been much less
      discussed in the literature. In rats, lacosamide shows restricted distribution to
      tissues, and the brain-to-plasma partition coefficient (Kp) is only 0.553. In
      this study, the brain disposition of lacosamide was evaluated in rat brains, and
      its neuropharmacokinetic parameters (i.e., protein binding and intracellular
      accumulation) were assessed using in vitro methods. Brain slice experiments and
      brain homogenate binding studies were performed for several drugs acting on the
      central nervous system, and drugs were assayed by using a liquid chromatography
      mass spectrometry system. By applying a combined approach, it was found that (1)
      the unbound volume of distribution in the brain for lacosamide (Vu,brain = 1.37)
      was lower than that of other classical anticonvulsants; (2) the unbound fraction
      of lacosamide in the brain (0.899) was slightly lower than its unbound fraction
      in plasma (0.96); (3) the unbound intracellular-to-extracellular concentration
      ratio of lacosamide was 1.233, meaning that lacosamide was accumulated in the
      intracellular space because of its physicochemical properties and zwitterionic
      structure; and (4) the unbound brain-to-plasma concentration ratio of lacosamide
      was lower than the total brain-to-plasma concentration ratio (Kp,uu,brain = 0.42
      vs. Kp = 0.553). In conclusion, the limited brain distribution of lacosamide is
      not related to its nonspecific protein-binding capacity; rather, an active
      transport mechanism across the blood-brain barrier may be involved, which reduces
      the anticonvulsant and/or antiepileptogenic actions of this drug.

PMID- 29019021
TI  - Analysis of histological findings obtained combining US/mp-MRI fusion-guided
      biopsies with systematic US biopsies: mp-MRI role in prostate cancer detection
      and false negative.
AB  - AIMS AND OBJECTIVES: To evaluate the diagnostic accuracy of mp-MRI correlating
      US/mp-MRI fusion-guided biopsy with systematic random US-guided biopsy in
      prostate cancer diagnosis. MATERIALS AND METHODS: 137 suspected prostatic
      abnormalities were identified on mp-MRI (1.5T) in 96 patients and classified
      according to PI-RADS score v2. All target lesions underwent US/mp-MRI fusion
      biopsy and prostatic sampling was completed by US-guided systematic random 12
      core biopsies. Histological analysis and Gleason score were established for all
      the samples, both target lesions defined by mp-MRI, and random biopsies. PI-RADS
      score was correlated with the histological results, divided in three groups
      (benign tissue, atypia and carcinoma) and with Gleason groups, divided in four
      categories considering the new Grading system of the ISUP 2014, using t test.
      Multivariate analysis was used to correlate PI-RADS and Gleason categories to PSA
      level and abnormalities axial diameter. When the random core biopsies showed
      carcinoma (mp-MRI false-negatives), PSA value and lesions Gleason median value
      were compared with those of carcinomas identified by mp-MRI (true-positives),
      using t test. RESULTS: There was statistically significant difference between PI
      RADS score in carcinoma, atypia and benign lesions groups (4.41, 3.61 and 3.24,
      respectively) and between PI-RADS score in Gleason < 7 group and Gleason > 7
      group (4.14 and 4.79, respectively). mp-MRI performance was more accurate for
      lesions > 15 mm and in patients with PSA > 6 ng/ml. In systematic sampling, 130
      (11.25%) mp-MRI false-negative were identified. There was no statistic difference
      in Gleason median value (7.0 vs 7.06) between this group and the mp-MRI true
      positives, but a significant lower PSA median value was demonstrated (7.08 vs
      7.53 ng/ml). CONCLUSION: mp-MRI remains the imaging modality of choice to
      identify PCa lesions. Integrating US-guided random sampling with US/mp-MRI fusion
      target lesions sampling, 3.49% of false-negative were identified.

PMID- 29019023
TI  - Challenges Associated with Estimating Utility in Wet Age-Related Macular
      Degeneration: A Novel Regression Analysis to Capture the Bilateral Nature of the
      Disease.
AB  - INTRODUCTION: The estimation of utility values for the economic evaluation of
      therapies for wet age-related macular degeneration (AMD) is a particular
      challenge. Previous economic models in wet AMD have been criticized for failing
      to capture the bilateral nature of wet AMD by modelling visual acuity (VA) and
      utility values associated with the better-seeing eye only. METHODS: Here we
      present a de novo regression analysis using generalized estimating equations
      (GEE) applied to a previous dataset of time trade-off (TTO)-derived utility
      values from a sample of the UK population that wore contact lenses to simulate
      visual deterioration in wet AMD. This analysis allows utility values to be
      estimated as a function of VA in both the better-seeing eye (BSE) and worse
      seeing eye (WSE). RESULTS: VAs in both the BSE and WSE were found to be
      statistically significant (p < 0.05) when regressed separately. When included
      without an interaction term, only the coefficient for VA in the BSE was
      significant (p = 0.04), but when an interaction term between VA in the BSE and
      WSE was included, only the constant term (mean TTO utility value) was
      significant, potentially a result of the collinearity between the VA of the two
      eyes. The lack of both formal model fit statistics from the GEE approach and
      theoretical knowledge to support the superiority of one model over another make
      it difficult to select the best model. CONCLUSION: Limitations of this analysis
      arise from the potential influence of collinearity between the VA of both eyes,
      and the use of contact lenses to reflect VA states to obtain the original
      dataset. Whilst further research is required to elicit more accurate utility
      values for wet AMD, this novel regression analysis provides a possible source of
      utility values to allow future economic models to capture the quality of life
      impact of changes in VA in both eyes. FUNDING: Novartis Pharmaceuticals UK
      Limited.

PMID- 29019024
TI  - Naphthalene glycosides in the Thai medicinal plant Diospyros mollis.
AB  - This study evaluated methanol extracts from the leaves and branches of the Thai
      medicinal plant Diospyros mollis (Ebenaceae). Seven triterpenes and 22 aromatic
      compounds, including five new compounds, were isolated, and their structures were
      determined. The new compounds had the following structures: diospyrol glycoside
      (makluoside A, 1), 8,8'-di-O-6-beta-D-apiofuranosyl-beta-D-glucopyranosyl-6,6'
      dimethyl-2,3'-binaphthalene-1-ol-1',4'- dione (makluoside B, 2), and 3-methyl-1,8
      naphthalenediol glycosides (makluosides C-E, 3-5). Makluoside B is the first
      example of a naphthoquinone glycoside that has both a 3-methyl-1,8
      naphthalenediol unit and a 5-hydroxy-7-methyl-1,4-naphthoquinone unit. The
      hyaluronidase inhibitory activity of the isolates was evaluated, revealing that
      one of the triterpene derivatives possessed moderate inhibitory activity.

PMID- 29019020
TI  - Pharmacodynamic and Pharmacokinetic Markers For Anti-angiogenic Cancer Therapy:
      Implications for Dosing and Selection of Patients.
AB  - Angiogenesis is integral to tumour growth and invasion, and is a key target for
      cancer therapeutics. However, for many of the licensed indications, only a modest
      clinical benefit has been observed for both monoclonal antibody and small
      molecule tyrosine kinase inhibitor anti-angiogenic therapy. Pre-clinical and
      clinical studies have attempted to evaluate circulating, imaging, genomic,
      pharmacokinetic, and pharmacodynamic markers that may aid both the selection of
      patients for treatment and define dosing. Correct dosing is likely to be critical
      in the context of vascular normalization to allow better delivery of concomitant
      anti-cancer therapy and novel imaging techniques hold much promise in the early
      evaluation of pharmacodynamic response to improve efficacy.

PMID- 29019026
TI  - Echocardiographic chamber quantification in a healthy Dutch population.
AB  - AIM: For accurate interpretation of echocardiographic measurements normative data
      are required, which are provided by guidelines. For this article, the hypothesis
      was that these cannot be extrapolated to the Dutch population, since in Dutch
      clinical practice often higher values are found, which may not be pathological
      but physiological. Therefore this study aimed to 1) obtain and propose normative
      values for cardiac chamber quantification in a healthy Dutch population and 2)
      determine influences of baseline characteristics on these measurements. METHODS:
      Prospectively recruited healthy subjects, aged 20-72 years (at least 28 subjects
      per age decade, equally distributed for gender) underwent physical examination
      and 2D and 3D echocardiography. Both ventricles and atria were assessed and
      volumes were calculated. RESULTS: 147 subjects were included (age 44 +/- 14
      years, 50% female). Overall, feasibility was good for both linear and volumetric
      measurements. Linear and volumetric parameters were consistently higher than
      current guidelines recommend, while functional parameters were in line with the
      guidelines. This was more so in the older population. 3D volumes were higher than
      2D volumes. Gender dependency was seen in all body surface area (BSA) corrected
      volumes and with increasing age, ejection fractions decreased. CONCLUSION: This
      study provides 2D and 3D echocardiographic reference ranges for both ventricles
      and atria derived from a healthy Dutch population. BSA indexed volumes are gender
      dependent, age did not influence ventricular volumes and a rise in blood pressure
      was independently associated with increased right ventricular volumes. The higher
      volumes found may be indicative for the Dutch population being the tallest in the
      world.

PMID- 29019025
TI  - An evidence-based medicine audit of the ophthalmic emergency services unit of
      King Abdulaziz University Hospital (KAUH).
AB  - PURPOSE: To improve the interventions provided for patients presenting with acute
      ophthalmic conditions to the ophthalmic emergency unit through applying the best
      available evidences from quality literature for managing such conditions.
      METHODS: A retrospective cohort study at a tertiary eye care university hospital
      in Riyadh, Saudi Arabia, involving a two-phase audit of diagnosis-intervention
      was conducted. The first phase was done retrospectively for the duration from
      April 1 to May 30, 2014, after disseminating the results of the first phase to
      King Abdulaziz University Hospital ophthalmology department staff, and the second
      phase was done retrospectively for the duration from November 1 to December 30,
      2015. The validity of outcomes was assessed through a literature search using
      Medline and the Cochrane Database of Systematic Reviews. The participants were
      masked on the study objectives to avoid Hawthorne's phenomenon (prescribing
      bias). RESULTS: In the first part of the audit, 73.2% out of 355 interventions
      were found to be evidence based. There was notable improvement of 80.9% in the
      number of evidence-based interventions in the second part of the audit. This
      improvement was statistically significant (p = 0.017). CONCLUSION: Evidence-based
      medicine audit can be a helpful tool to assess the performance and can lead to
      quality improve of the provided care by reducing the number of medical errors and
      refining medical decisions and interventions.

PMID- 29019027
TI  - Acculturation, Acculturative Stress, and Depressive Symptoms in International
      Migrants: A Study with Vietnamese Women in South Korea.
AB  - Globally, there have been increasing numbers of migrant women; these women are at
      an increased risk for depressive symptoms. The purpose of this study was to
      examine the associations among acculturation, acculturative stress and depressive
      symptoms in Vietnamese women who migrated to South Korea through marriages. We
      hypothesized that acculturative stress would serve as a mediator in the
      relationship between acculturation and depressive symptoms. Our findings from
      surveys with 217 Vietnamese immigrant women showed that the indirect effect of
      acculturation on depressive symptoms, mediated through acculturative stress [-
      .15 (.04)], was significant (bias corrected 95% confidence interval for the
      indirect effect = - .25, - .08). Low levels of acculturation increased
      acculturative stress, which in turn led to the elevated symptoms of depression.
      Our findings not only illuminate the adaptation processes of international,
      female migrants but also suggest avenues to protect and promote their mental well
      being.

PMID- 29019028
TI  - Application of a full model-based iterative reconstruction (MBIR) in 80 kVp ultra
      low-dose paranasal sinus CT imaging of pediatric patients.
AB  - OBJECTIVE: To evaluate the clinical application of a full model-based iterative
      reconstruction (MBIR) algorithm in the ultra-low-dose paranasal sinus CT imaging
      of children. MATERIALS AND METHODS: In the first phase, 16 low-dose CT
      dacryocystography (DCG) (80 kV/64 mAs) scans were reconstructed with MBIR and
      filtered back-projection (FBP) to demonstrate noise reduction capability of MBIR.
      MBIR images were also compared with the images of 21 standard-dose paranasal
      sinus patients reconstructed with adaptive statistical iterative reconstruction
      (ASIR) algorithm. In the second phase, 14 pediatric tumors patients (images with
      ASIR in the initial scan) who came for follow-up paranasal sinus CT scan were
      prospectively enrolled with reduced radiation and MBIR algorithm. In both study
      phases, image noise and the contrast noise ratio (CNR) of sphenoid was measured;
      and subjective image quality was evaluated. CTDIvol and DLP were recorded, and
      effective dose calculated. RESULTS: The CTDIvol value for the DCG group was 63.9%
      lower than the standard-dose sinus group (1.09 +/- 0.01 mGy vs. 3.02 +/- 0.35
      mGy). Compared with the ASIR reconstruction in the standard-dose sinus patient
      group, images with MBIR in the ultra-low-dose DCG group had 39.9% lower noise
      (9.5 +/- 0.8HU vs. 15.8 +/- 3.3HU) and 63.6% higher CNR (14.4 +/- 4.7 vs. 8.8 +/-
      2.2), with similar subjective image quality score. For the tumor patients, 65.5%
      dose reduction was achieved. Subjective quality scores were similar between the
      initial and follow-up scans. Objective noise was significantly lower for the
      follow-up group. CONCLUSION: MBIR provided equal or better image quality with
      significantly reduced radiation dose in paranasal sinus CT imaging of pediatric
      patients compared with standard-dose CT with ASIR algorithm.

PMID- 29019030
TI  - Cloning and upscale production of monoamine oxidase N (MAO-N D5) by Pichia
      pastoris.
AB  - OBJECTIVE: To clone monoamine oxidase N, that catalyses the selective oxidative
      deamination or deracemisation of amines into imines, in Pichia pastoris and prove
      the importance of choosing the proper expression system for its recombinant
      production. RESULTS: Monoamine oxidase, originating from Aspergillus niger and
      subjected to directed evolution (MAO-N D5), was cloned and expressed in Pichia
      pastoris CBS7435 MutS strain for the first time. Various transformants were
      screened at microscale level. The production of the clone expressing the most
      active enzyme was scaled-up to a 1.5 l fermenter and preparation of MAO-N D5 as a
      crude enzyme extract was optimised. The obstacles in the production of the enzyme
      in both expression systems, Escherichia coli and P. pastoris, are discussed and
      demonstrated. CONCLUSIONS: There was an improvement in specific productivity,
      which was 83 times higher in P. pastoris, clearly proving the importance of
      choosing the right expression host system for the specific enzymes.

PMID- 29019029
TI  - Hippocampal Acetylation may Improve Prenatal-Stress-Induced Depression-Like
      Behavior of Male Offspring Rats Through Regulating AMPARs Expression.
AB  - This study is to determine the role and mechanism of hippocampal acetylation in
      prenatal stress (PS) induced depression-like behavior of male offspring rats. PS
      induced depression rat model was established. Sucrose preference and forced swim
      test were used to observe the behavior changes of male offspring rats.
      Hippocampal acetylation was induced by Trichostatin A injection. Quantitative
      real-time PCR and Western blot were used to determine the changes of AMPARs in
      acetylated hippocampus. The behavioral tests proved that AMPA was involved in the
      PS-induced depression-like behavior in offspring rats. Hippocampal acetylation
      significantly increased the preference to sucrose of PS-induced offspring rats
      and reduced the immobile time in forced swimming test, suggesting that
      acetylation could improve PS-induced depression-like behaviors. In addition, PS
      inhibited the expression levels of GluA1-3 subunits of AMPARs in the offspring
      hippocampus, while Hippocampal acetylation could reverse this effect by
      increasing GluA1-3 expression. PS-induced reduction of GluA1-3 subunits of AMPARs
      may be an important potential mechanism of offspring depression. Hippocampal
      acetylation may improve PS-induced offspring depression-like behavior through the
      enhanced expression of AMPARs (GluA1-3 subunits).

PMID- 29019031
TI  - Effects of different soil remediation methods on inhibition of lead absorption
      and growth and quality of Dianthus superbus L.
AB  - Heavy metal pollution in soil poses a serious threat to the growth of plants used
      in traditional Chinese medicine. Therefore, a pot experiment was conducted to
      study the effects of various soil remediation methods on the performance of Herba
      Dianthi (Dianthus superbus L.) grown on Pb-contaminated soil. The results show
      that inoculation of Herba Dianthi with arbuscular mycorrhizal fungi (AMF) led to
      a significant reduction in Pb uptake (P< 0.05), and increased root development
      and root-to-shoot ratio compared to untreated control plants, along with the
      highest content of active components. When planting with Trifolium repens, the
      reduction effect of Pb absorption was insignificant. Herba Dianthi showed
      improved growth and active ingredients, and the lowest Pb content, with AMF
      inoculation. The addition of EDTA decreased the growth of Herba Dianthi, but
      promoted the absorption of Pb. The inhibition of tumor cells was highest in E2.
      In conclusion, inoculation with AMF can ensure that plant lead content meets
      testing standards, helping to improve the quality of medicinal herbs.

PMID- 29019033
TI  - Polyethyleneimine and Chitosan Polymer-Based Mucoadhesive Liquid Crystalline
      Systems Intended for Buccal Drug Delivery.
AB  - The buccal mucosa is accessible, shows rapid repair, has an excellent blood
      supply, and shows the absence of the first-pass effect, which makes it a very
      attractive drug delivery route. However, this route has limitations, mainly due
      to the continuous secretion of saliva (0.5 to 2 L/day), which may lead to
      dilution, possible ingestion, and unintentional removal of the active drug.
      Nanotechnology-based drug delivery systems, such as liquid crystalline systems
      (LCSs), can increase drug permeation through the mucosa and thereby improve drug
      delivery. This study aimed at developing and characterizing the mechanical,
      rheological, and mucoadhesive properties of four liquid crystalline precursor
      systems (LCPSs) composed of four different aqueous phases (i) water (FW), (ii)
      chitosan (FC), (iii) polyethyleneimine (FP), or (iv) both polymers (FPC); oleic
      acid was used as the oil phase, and ethoxylated and propoxylated cetyl alcohol
      was used as the surfactant. Polarized light microscopy and small-angle X-ray
      scattering indicated that all LCPSs formed liquid crystalline states after
      incorporation of saliva. Rheological, texture, and mucoadhesive assays showed
      that FPC had the most suitable characteristics for buccal application. In vitro
      release study showed that FPC could act as a controlled drug delivery system.
      Finally, based on in vitro cytotoxicity data, FPC is a safe buccal drug delivery
      system for the treatment of several buccal diseases.

PMID- 29019034
TI  - Working Life Expectancy at Age 50 in the United States and the Impact of the
      Great Recession.
AB  - A key concern about population aging is the decline in the size of the
      economically active population. Working longer is a potential remedy. However,
      little is known about the length of working life and how it relates to
      macroeconomic conditions. We use the U.S. Health and Retirement Study for 1992
      2011 and multistate life tables to analyze working life expectancy at age 50 and
      study the impact of the Great Recession in 2007-2009. Despite declines of one to
      two years following the recession, in 2008-2011, American men aged 50 still spent
      13 years, or two-fifths of their remaining life, working; American women of the
      same age spent 11 years, or one-third of their remaining life, in employment.
      Although educational differences in working life expectancy have been stable
      since the mid-1990s, racial differences started changing after the onset of the
      Great Recession. Our results show that although Americans generally work longer
      than people in other countries, considerable subpopulation heterogeneity exists.
      We also find that the time trends are fluctuating, which may prove troublesome as
      the population ages. Policies targeting the weakest performing groups may be
      needed to increase the total population trends.

PMID- 29019032
TI  - Nanotechnology as a Delivery Tool for Precision Cancer Therapies.
AB  - Genomic analyses from patients with cancer have improved the understanding of the
      genetic elements that drive the disease, provided new targets for treating this
      relentless disease, and offered criteria for stratifying patient populations that
      will benefit most from treatments. In the last decade, several new targeted
      therapies have been approved by the FDA based on these omics findings, leading to
      significantly improved survival and quality of life for select patient
      populations. However, many of these precision medicines, e.g., nucleic acid-based
      therapies and antibodies, suffer from poor plasma stability, suboptimal
      pharmacokinetic properties, and immunological toxicities that prohibit their
      clinical translation. Nanotechnology is being explored as a delivery platform
      that can enable the successful delivery of these precision medicine treatments
      without these limitations. These precision nanomedicines are able to protect the
      cargo from degradation or premature/burst release prior to accumulation at the
      tumor site and improve the selectivity to cancer cells by incorporating ligands
      that can target receptors overexpressed on the cancer cell surface. Here, we
      review the development of several precision nanomedicines based on genomic
      analysis of clinical samples, actively targeted nanoparticle delivery systems in
      the clinic, and the pathophysiological barriers of the tumor microenvironment.
      Successful translation of these precision nanomedicine initiatives will require
      an effective collaboration between basic and clinical investigators to match the
      right patient with the right therapies and to deliver them at therapeutic
      concentrations which will improve overall treatment responses.

PMID- 29019035
TI  - Concanavalin A Induces Cortical Neuron Apoptosis by Causing ROS Accumulation and
      Tyrosine Kinase Activation.
AB  - The lectin, concanavalin A (Con A), is the most extensively investigated member
      of the lectin family of plant proteins, but its effects on cortical neurons and
      astrocytes are poorly understood. In cultured cortical neurons and astrocytes,
      Con A exhibited dose-dependent neurotoxicity, but this was not observed in
      astrocytes. Similarly, in the cortical areas of rat brains, intracranial
      administration of Con A caused neuronal but no astrocyte damage. Methyl-alpha-D
      mannopyranoside, a competitor of Con A, blocked Con A-induced cell death, whereas
      AMPA/KA receptor antagonists showed partial blocking effects. Furthermore, the
      mRNA levels of TNF-alpha, IL-1beta, and IL-6 were elevated in astrocytes and
      cortical neurons treated with Con A. Intracellular reactive oxygen species (ROS)
      levels were increased in Con A-treated cortical neurons, and N-acetyl-cysteine
      (NAC, an antioxidant) and diphenyleneiodonium (DPI, a NADPH oxidase inhibitor)
      reduced intracellular ROS accumulation. Likewise, AG556 (a TNF-alpha inhibitor)
      and AG82 (a tyrosine kinase inhibitor) both reduced Con A-induced intracellular
      ROS accumulation. Furthermore, Con A-induced tyrosine phosphorylation was
      decreased by NAC and by AG556. Taken together, Con A-induced apoptosis in
      cortical neurons occurred as a sequel to Con A binding to neuronal glycoproteins
      and intracellular ROS accumulation. Interestingly, Con A-induced cellular damage
      was observed in cortical neurons but not in astrocytes or microglia.

PMID- 29019036
TI  - Neural networks underlying trait aggression depend on MAOA gene alleles.
AB  - Low expressing alleles of the MAOA gene (MAOA-L) have been associated with an
      increased risk for developing an aggressive personality. This suggests an MAOA-L
      specific neurobiological vulnerability associated with trait aggression. The
      neural networks underlying this vulnerability are unknown. The present study
      investigated genotype-specific associations between resting state brain networks
      and trait aggression (Buss-Perry Aggression Questionnaire) in 82 healthy
      Caucasian males. Genotype influences on aggression-related networks were studied
      for intrinsic and seed-based brain connectivity. Intrinsic connectivity was
      higher in the ventromedial prefrontal cortex (VMPFC) of MAOA-L compared to high
      expressing allele (MAOA-H) carriers. Seed-based connectivity analyses revealed
      genotype differences in the functional involvement of this region. MAOA genotype
      modulated the relationship between trait aggression and VMPFC connectivity with
      supramarginal gyrus (SMG) and areas of the default mode network (DMN). Separate
      analyses for the two groups were performed to better understand how the genotype
      modulated the relationship between aggression and brain networks. They revealed a
      positive correlation between VMPFC connectivity and aggression in right angular
      gyrus (AG) and a negative correlation in right SMG in the MAOA-L group. No such
      effect emerged in the MAOA-H carriers. The results indicate a particular
      relevance of VMPFC for aggression in MAOA-L carriers; in specific, a detachment
      from the DMN along with a strengthened coupling to the AG seems to go along with
      lower trait aggression. MAOA-L carriers may thus depend on a synchronization of
      emotion regulation systems (VMPFC) with core areas of empathy (SMG) to prevent
      aggression.

PMID- 29019038
TI  - Utilisation and Safety of Deferasirox: Results from an Observational Cohort Study
      in England.
AB  - INTRODUCTION: Deferasirox (EXJADE(r), Novartis, UK) is an oral iron-chelating
      agent primarily used to reduce chronic iron overload in patients receiving blood
      transfusions for various chronic anaemias and some non-transfusion dependant
      anaemias. OBJECTIVE: The aim of this study was to examine the utilisation and
      safety of deferasirox used in general practice in England. METHOD: A single
      exposure observational cohort study design was used. Patients were identified
      from dispensed prescriptions for deferasirox between September 2006 and September
      2014. Outcome data were collected via postal questionnaires sent to prescribers
      >= 6 months after first dispensed prescription for an individual patient. Summary
      descriptive statistics were calculated. RESULTS: The evaluable cohort consisted
      of 122 patients, of which 41.8% were aged 2-17 years. Frequent reasons for
      prescribing were sickle cell anaemia (27/103 where specified, 26.2%) and beta
      thalassaemia (26, 25.2%). The majority of patients (43/51, 84.3%) were prescribed
      the licensed doses of 10 or 20 mg/kg/day at start. Prior measurements of serum
      creatinine were only reported for a small proportion this study (18/122, 14.8%).
      In total, 91 incident events were reported, including two of raised serum
      creatinine. CONCLUSION: These results show that deferasirox is largely being
      prescribed for its licensed indications in general practice in England and events
      reported were consistent with the known safety profile.

PMID- 29019037
TI  - Role of sulfate, chloride, and nitrate anions on the degradation of
      fluoroquinolone antibiotics by photoelectro-Fenton.
AB  - Taking ciprofloxacin (CIP) as a fluoroquinolone antibiotic model, this work
      explores the role of common anions (sulfate, nitrate, and chloride) during the
      application of photoelectro-Fenton (PEF) at natural pH to degrade this type of
      compound in water. The system was composed of an IrO2 anode, Ti, or gas diffusion
      electrode (GDE) as cathode, Fe2+, and UV (254 nm). To determine the implications
      of these anions, the degradation pathway and efficiency of the PEF sub-processes
      (UV photolysis, anodic oxidation, and electro-Fenton at natural pH) were studied
      in the individual presence of the anions. The results highlight that degradation
      routes and kinetics are strongly dependent on electrolytes. When chloride and
      nitrate ions were present, indirect electro-chemical oxidation was identified by
      electro-generated HOCl and nitrogenated oxidative species, respectively.
      Additionally, direct photolysis and direct oxidation at the anode surface were
      identified as degradation routes. As a consequence of the different pathways, six
      primary CIP by-products were identified. Therefore, a scheme was proposed
      representing the pathways involved in the degradation of CIP when submitted to
      PEF in water with chloride, nitrate, and sulfate ions, showing the complexity of
      this process. Promoted by individual and synergistic actions of this process, the
      PEF system leads to a complete elimination of CIP with total removal of
      antibiotic activity against Staphylococcus aureus and Escherichia coli, and
      significant mineralization. Finally, the role of the anions was tested in
      seawater containing CIP, in which the positive contributions of the anions were
      partially suppressed by its OH radical scavenger action. The findings are of
      interest for the understanding of the degradation of antibiotics via the PEF
      process in different matrices containing sulfate, nitrate, and chloride ions.

PMID- 29019039
TI  - Portrayals of Psychiatry and Mental Disorders in Hispanic Rock Music.

PMID- 29019040
TI  - Migraine-Like Visual Auras Among Traumatized Cambodians with PTSD: Fear of Ghost
      Attack and Other Disasters.
AB  - This article profiles visual auras among traumatized Cambodian refugees attending
      a psychiatric clinic. Thirty-six percent (54/150) had experienced an aura in the
      previous 4 weeks, almost always phosphenes (48% [26/54]) or a scintillating
      scotoma (74% [40/54]). Aura and PTSD were highly associated: patients with visual
      aura in the last month had greater PTSD severity, 3.6 (SD = 1.8) versus 1.9 (SD =
      1.6), t = 10.2 (df = 85), p < 0.001, and patients with PTSD had a higher rate of
      visual aura in the last month, 69% (22/32) versus 13% (7/55), odds ratio 15.1
      (5.1-44.9), p < 0.001. Patients often had a visual aura triggered by rising up to
      the upright from a lying or sitting position, i.e., orthostasis, with the most
      common sequence being an aura triggered upon orthostasis during a migraine,
      experienced by 60% of those with aura. The visual aura was often catastrophically
      interpreted: as the dangerous assault of a supernatural being, most commonly the
      ghost of someone who died in the Pol Pot period. Aura often triggered flashback.
      Illustrative cases are provided. The article suggests the existence of local
      biocultural ontologies of trauma as evinced by the centrality of visual auras
      among Cambodian refugees.

PMID- 29019041
TI  - Remediation of persistent organic pollutant-contaminated soil using biosurfactant
      enhanced electrokinetics coupled with a zero-valent iron/activated carbon
      permeable reactive barrier.
AB  - Zero-valent iron/activated carbon (Fe/C) particles can degrade persistent organic
      pollutants via micro-electrolysis and therefore, they may be used to develop
      materials for permeable reactive barriers (PRBs). In this study, surfactant
      enhanced electrokinetics (EK) was coupled with a Fe/C-PRB to treat phenanthrene
      (PHE) and 2,4,6-trichlorophenol (TCP) co-contaminated clay soil. An environment
      friendly biosurfactant, rhamnolipid, was selected as the solubility-enhancing
      agent. Five bench-scale tests were conducted to investigate the performance of EK
      PRB on PHE and TCP removal from soil as well as the impact of pH and rhamnolipid
      concentration. The results show that both PHE and TCP, driven by electro-osmotic
      flow (EOF), moved toward the cathode and reacted with the Fe/C-PRB. Catholyte
      acidification and rhamnolipid concentration increase improved the removal
      efficiencies of PHE and TCP. The highest removal efficiency of PHE in soil column
      was five times the efficiency of the control group on which only EK was applied
      (49.89 versus 9.40%). The highest removal efficiency of TCP in soil column was
      4.5 times the efficiency of the control group (64.60 versus 14.30%). Desorption
      and mobility of PHE and TCP improved with the increase of rhamnolipid
      concentration when this exceeded the critical micelle concentration. This study
      indicates that the combination of EK and a Fe/C-PRB is efficient and promising
      for removing persistent organic pollutants (POPs) from contaminated soil with the
      enhancement of rhamnolipid.

PMID- 29019043
TI  - Large Lateral Photovoltaic Effect in MoS2/GaAs Heterojunction.
AB  - Molybdenum disulfide (MoS2) nanoscaled films are deposited on GaAs substrates via
      magnetron sputtering technique, and MoS2/GaAs heterojunctions are fabricated. The
      lateral photovoltaic effect (LPE) of the fabricated MoS2/GaAs heterojunctions is
      investigated. The results show that a large LPE can be obtained in the MoS2/n
      GaAs heterojunction. The LPE exhibits a linear dependence on the position of the
      laser illumination and the considerably high sensitivity of 416.4 mV mm-1. This
      sensitivity is much larger than the values in other reported MoS2-based devices.
      Comparatively, the LPE in the MoS2/p-GaAs heterojunction is much weaker. The
      mechanisms to the LPE are unveiled by constructing the energy-band alignment of
      the MoS2/GaAs heterojunctions. The excellent LPE characteristics make MoS2 films
      combined with GaAs semiconductors promising candidates for the application of
      high-performance position-sensitive detectors.

PMID- 29019042
TI  - Long-term outcomes of adult medulloblastoma patients treated with radiotherapy.
AB  - Medulloblastoma (MB) is rare in adults and treatment guidelines are consequently
      not well-established. Few modern series have reported long-term follow-up and
      treatment sequelae. We examined long-term outcomes of adult MB patients at one
      institution. Records of 29 consecutive patients (18 male, 11 female) aged >= 18
      years who received radiotherapy (RT) for primary MB from 1990 to 2016 were
      reviewed. Median age at diagnosis was 28 years (range 18-72 years). Seventeen
      patients were standard risk and 12 were high risk. Nineteen patients had gross
      total resection, seven had subtotal resection, and three had biopsy only. Median
      craniospinal irradiation and boost doses were 36 Gy (range 23.4-39.6 Gy) and 55.8
      Gy (range 54-59.4 Gy), respectively. Of 24 patients receiving chemotherapy, 20
      received concurrent + adjuvant and 4 received adjuvant only. At median follow-up
      of 9.0 years (range 1.1-20.5 years), five patients recurred: four in the
      posterior fossa and one in both the posterior fossa and above the tentorium. Five
      patients died: two of disease progression and three after possible treatment
      complications (seizure, lobar pneumonia, and multifactorial sepsis). At last
      follow-up, 23 patients were alive with no evidence of disease. Long-term effects
      include executive dysfunction (n = 17), weakness/ataxia (n = 16), and
      depression/anxiety (n = 13). Kaplan-Meier estimates of 10-year overall survival
      and failure-free survival are 83% (95% confidence interval [CI] 59-93%) and 79%
      (CI 55-91%), respectively. Despite encouraging disease control in this cohort,
      long-term sequelae may limit quality of life. Multimodality pediatric regimens
      using lower RT doses may be considered to reduce treatment-related morbidity.

PMID- 29019044
TI  - Hobnail Variant of Papillary Thyroid Carcinoma: a Literature Review.
AB  - Papillary thyroid carcinoma is the most common thyroid malignancy and it is
      usually associated with a good prognosis. However, recurrence, metastases, and
      cancer death may occur in 10 to 15% of patients with more aggressive types of
      papillary thyroid carcinoma, such as tall cell, columnar cell, solid variant, or
      the more recently described hobnail variant of papillary thyroid carcinoma.
      Papillary thyroid carcinoma with a prominent hobnail pattern is a moderately
      differentiated papillary thyroid carcinoma variant with aggressive clinical
      behavior and significant mortality. The hobnail variant of papillary thyroid
      carcinoma shows prominent hobnail features, which have also been referred to as
      micropapillary. The typical hobnail/micropapillary morphological features show
      loss of cellular polarity/cohesiveness and support an epithelial-mesenchymal
      transition as a possible mechanism of metastasis. BRAF p.V600E is the most common
      mutation in papillary thyroid carcinoma, including the hobnail variant; recent
      and continuing studies are focused on defining other molecular anomalies that may
      be useful for prognostic stratification and may provide therapeutic targets.

PMID- 29019046
TI  - Effect of Reminding Patients to Complete Fecal Immunochemical Testing: A
      Comparative Effectiveness Study of Automated and Live Approaches.
AB  - BACKGROUND: The Community Preventive Services Task Force recommends multi
      component interventions, including patient reminders, to improve uptake of
      colorectal cancer screening. OBJECTIVE: We sought to compare the effectiveness of
      different forms of reminders for a direct-mail fecal immunochemical test (FIT)
      program. DESIGN: Patient-randomized controlled trial. PARTICIPANTS: 2772 adults
      aged 50-75, not up to date with colorectal cancer screening recommendations, with
      a clinic visit in the previous year at any of four participating health center
      clinics. INTERVENTION: Participants were mailed an introductory letter and FIT.
      Those who did not complete their FIT within 3 weeks were randomized to receive
      (1) a reminder letter, (2) two automated phone calls, (3) two text messages, (4)
      a live phone call, (5) a reminder letter and a live phone call, (6) two automated
      phone calls and a live phone call, or (7) two text messages and a live phone
      call. Patients with a patient portal account were sent two email reminders, but
      were not randomized. MAIN MEASURES: FIT return rates for each group, 6 months
      following randomization. KEY RESULTS: A total of 255 (10%) participants returned
      their FIT within 3 weeks of the mailing. Among randomized participants (n =
      2010), an additional 25.5% returned their FITs after reminders were delivered
      (estimated overall return rate = 32.7%). In intention-to-treat analysis, compared
      to the group allocated to receive a reminder letter, return rates were higher for
      the group assigned to receive the live phone call (OR = 1.51 [1.03-2.21]) and
      lower for the group assigned to receive text messages (OR = 0.66 [0.43-0.99]).
      Reminder effectiveness differed by language preference. CONCLUSIONS: Our data
      suggest that FIT reminders that included a live call were more effective than
      reminders that relied solely on written communication (a text message or letter).
      TRIAL REGISTRATION: ClinicalTrials.gov/ctc2/show/NCT01742065 .

PMID- 29019045
TI  - The characteristics of coronary stenosis in 11,267 patients from Southwest China:
      a retrospective study.
AB  - The characteristics of coronary stenosis vary among the different countries or
      areas. 11,267 patients who have undergone coronary angiography (CAG) from three
      Southwest China hospitals were investigated. Patient characteristics, coronary
      stenosis and stent-implant information were recorded and analyzed according to
      two criteria: "visible stenosis" and ">= 50% stenosis". The patients who have
      undergone CAG increased year by year, with patients from 60 to 69 years-old
      taking the highest ratio (34.69%). Based on the ">= 50% stenosis" criteria, the
      stenotic frequency was 40.54% for Southwest China patients getting CAG. Only
      8.14% patients suffered >= 3 stenotic vessels, while 11.58 and 20.82% patients
      had 2 or 1 stenotic vessel, respectively. However, when using the "visible
      stenosis" criteria, the stenotic frequency increased to 64.68%. The prevalence of
      stenosis increased with age based on the "visible stenosis" criteria. There were
      more male patients with stenosis than female except patients over 80 years old.
      The stenosis affected almost all main coronary arteries and their branches, with
      the most affected artery being the left anterior descending artery. There were
      3246 cases (28.8%) implanted with 5423 stents with a concurrent age-dependent
      increasing tendency for stent-implant frequency and average implanted stent
      number. The numbers of patients who have undergone CAG and suffered from CVD
      increased rapidly. In these patients, positive rate of CAG was 64.67%, which
      increased to 72.2% in patients over 60-years old. The incidence of >= 75%
      stenosis and multiple stenosis increased with age, however it should be noticed
      there were 18.93% for >= 75% stenosis and 19.52% for multiple stenosis in
      patients under 40 years old.

PMID- 29019047
TI  - Autoantibodies against interleukin-21 correlate with disease activity in patients
      with rheumatoid arthritis.
AB  - The objective of this study is to investigate the levels of interleukin (IL)-21
      and autoantibodies (AAbs) against IL-21 and their association with clinical
      characteristics and laboratory parameters in patients with rheumatoid arthritis
      (RA). One hundred twenty-six patients with RA, 69 patients with osteoarthritis
      (OA), and 88 healthy controls (HC) were included in this study. The levels of IL
      21 and AAbs against IL-21 in the serum were measured using enzyme-linked
      immunosorbent assay (ELISA). The correlation between the levels of IL-21 and anti
      IL-21 AAbs with clinical and laboratory parameters was evaluated. The results
      showed that the concentration of IL-21 was significantly higher in the serum of
      patients with RA (15.58 +/- 3.22 ng/ml) than OA (1.80 +/- 0.99 ng/ml) and HC
      (0.07 +/- 0.03 ng/ml, p < 0.01). The levels of IL-21 in the serum correlated with
      erythrocyte sedimentation rate (ESR) in patients with RA (r = 0.435, p < 0.01).
      Anti-IL-21 AAbs could be detected in RA patients. The median AU value of AAbs
      against IL-21 was significantly higher in serum of RA (47.90) than in that of OA
      (15.17) and HC (8.19, p < 0.01). The titers of AAbs against IL-21 correlated with
      Disease Activity Score-28 (DAS28) (r = 0.449, p < 0.001), ESR (r = 0.386, p <
      0.001), and CRP (r = 0.241, p = 0.03). Both IL-21 and AAbs against IL-21 are
      elevated in RA. The levels of AAbs against IL-21 correlate with disease activity,
      which suggests that anti-IL-21 AAbs may play a role in the pathogenesis of RA.

PMID- 29019048
TI  - Parental Action and Referral Patterns in Spatial Clusters of Childhood Autism
      Spectrum Disorder.
AB  - Sociodemographic factors have long been associated with disparities in autism
      spectrum disorder (ASD) diagnosis. Studies that identified spatial clustering of
      cases have suggested the importance of information about ASD moving through
      social networks of parents. Yet there is no direct evidence of this mechanism.
      This study explores the help-seeking behaviors and referral pathways of parents
      of diagnosed children in Costa Rica, one of two countries in which spatial
      clusters of cases have been identified. We interviewed the parents of 54
      diagnosed children and focused on social network connections that influenced
      parents' help seeking and referral pathways that led to assessment. Spatial
      clusters of cases appear to be a result of seeking private rather than public
      care, and private clinics are more likely to refer cases to the diagnosing
      hospital. The referring clinic rather than information spread appears to explain
      the disparities.

PMID- 29019049
TI  - Raman Spectra and Bulk Modulus of Nanodiamond in a Size Interval of 2-5 nm.
AB  - Nanodiamond in a 2-5-nm size interval (which is typical for an appearance of
      quantum confinement effect) show Raman spectra composed of 3 bands at 1325, 1600,
      and 1500 cm-1 (at the 458-nm laser excitation) which shifts to 1630 cm-1 at the
      257-nm laser excitation. Contrary to sp2-bonded carbon, relative intensities of
      the bands do not depend on the 458- and 257-nm excitation wavelengths, and a
      halfwidth and the intensity of the 1600 cm-1 band does not change visibly under
      pressure at least up to 50 GPa. Bulk modulus of the 2-5-nm nanodiamond determined
      from the high-pressure study is around 560 GPa. Studied 2-5-nm nanodiamond was
      purified from contamination layers and dispersed in Si or NaCl.

PMID- 29019050
TI  - Impacting Entry into Evidence-Based Supported Employment: A Population-Based
      Empirical Analysis of a Statewide Public Mental Health Program in Maryland.
AB  - We use discrete-time survival regression to study two empirical issues relating
      to take-up of individual placement and support (IPS) supported employment (SE)
      services for persons with serious mental illness: (1) the influence of client
      characteristics on take-up probability, and (2) the possible impacts of a major
      recent initiative in one state (Maryland) to overcome barriers to IPS-SE
      expansion. Our longitudinal analysis of population-based Medicaid cohorts, during
      2002-2010, provides tentative evidence of positive state initiative impacts on SE
      take-up rates, and evidence of effects on take-up for clients' diagnoses, prior
      work-history, health and demographic characteristics, and geographic
      accessibility to SE providers.

PMID- 29019051
TI  - The link between narcolepsy and autonomic cardiovascular dysfunction: a
      translational perspective.
AB  - Narcolepsy is a rare disease that entails excessive daytime sleepiness, often
      associated with sudden episodes of muscle weakness known as cataplexy. Narcolepsy
      with cataplexy (NC) is due to the loss of hypothalamic neurons that release the
      neuropeptides orexin A and B. Orexin neuron projections prominently target brain
      structures involved in wake-sleep state switching and the central autonomic
      network. This review provides an updated summary of the links between NC and
      autonomic cardiovascular dysfunction from a translational perspective. The
      available evidence suggests that, compared with control subjects, the heart rate
      in patients and animal models with NC is variable during wakefulness and normal
      to high during sleep. Responses of the heart rate to internal stimuli (arousal
      from sleep, leg movements during sleep, defense response) are blunted. These
      alterations result from orexin deficiency and, at least during wakefulness before
      sleep, involve decreased parasympathetic modulation of the heart rate. On the
      other hand, NC in patients and animal models is associated with a blunted fall in
      arterial blood pressure from wakefulness to sleep, and particularly to the REM
      state, coupled to a variable decrease in arterial blood pressure during
      wakefulness. The former effect is caused, at least in part, by deranged control
      of the heart, whereas the latter may be due to decreased vasoconstrictor
      sympathetic activity. Systematic studies are warranted to help clarify whether
      and how the links between NC and autonomic dysfunction impact on the
      cardiovascular risk of patients with narcolepsy.

PMID- 29019052
TI  - Flocculation of coal washing wastewater using polysaccharide produced by
      Paenibacillus mucilaginosus WL412.
AB  - Natural polymeric flocculant shows effectiveness in wastewater treatment without
      increasing the environmental burden. The extracellular substance produced by
      Paenibacillus mucilaginosus WL412 was identified as an anionic polysaccharide
      composed of five types of monosaccharides, namely, D-mannose, D-glucuronic acid,
      D-glucose, D-galactose, and L-fucose with the molar ratio of 2.8:1.2:2.0:1.8:0.8.
      The purified polysaccharide, POS412, presented high efficiency in flocculating
      coal washing wastewater and kaolin suspension without the assistance of inorganic
      coagulants. Addition of POS412 resulted in the polymer bridging phenomenon in
      suspensions, which was observed by means of scanning electron microscopic
      imaging, size grading, and zeta-potential analyses. More importantly, POS412
      exhibited satisfactory stability after storage in various conditions. The
      flocculation rate was more than 91% for coal washing wastewater when POS412 was
      stored for 264 h in the wide range of pH (3-11) and temperature (20-50  degrees
      C) before use. Results indicate that POS412 is a competent bioflocculant for
      wastewater treatment.

PMID- 29019053
TI  - Lewis X-Carrying Neoglycolipids Evoke Selective Apoptosis in Neural Stem Cells.
AB  - N-glycans carrying the Lewis X trisaccharide [Galbeta1-4 (Fucalpha1-3) GlcNAc]
      are expressed by neural stem cells (NSCs) exclusively before differentiation, and
      they actively contribute to the maintenance of stemness of these cells. To
      address the functional roles of the Lewis X-mediated molecular interactions in
      NSCs, we created a series of synthetic neoglycolipids that contained a Lewis X
      carrying glycan connected to an acyl chain through an amide bond. The
      neoglycolipids formed aqueous micelles displaying functional Lewis X glycotopes.
      Surprisingly, the neoglycolipid micelles evoked selective apoptosis in
      undifferentiated NSCs, whereas their differentiated cells remained unaffected.
      The apoptotic activity depended on the structural integrity of the Lewis X
      glycotopes and also on the length of the acyl chain, with an optimum length of
      C18. We propose hypothetical functional mechanisms of the neoglycolipid, which
      involves selective NSC targeting with Lewis X glycan and apoptotic signaling by
      the intracellular release of fatty acids. This serendipitous finding may offer a
      new strategy for controlling neural cell fates using artificial glycoclusters.

PMID- 29019054
TI  - The Happiest Kids on Earth. Gender Equality and Adolescent Life Satisfaction in
      Europe and North America.
AB  - Cross-national differences in adolescent life satisfaction in Europe and North
      America are consistent, but remain poorly understood. While previous studies have
      predominantly focused on the explanatory role of economic factors, such as
      national wealth and income equality, they revealed weak associations, at most.
      This study examines whether societal gender equality can explain the observed
      cross-national variability in adolescent life satisfaction. Based on the
      assumption that gender equality fosters a supportive social context, for example
      within families through a more equal involvement of fathers and mothers in child
      care tasks, adolescent life satisfaction was expected to be higher in more gender
      equal countries. To test this hypothesis, national-level data of gender equality
      (i.e., women's share in political participation, decision making power, economic
      participation and command over resources) were linked to data from 175,470
      adolescents aged 11-16 years old (M age  = 13.6, SD = 1.64, 52% girls) from 34
      European and North American countries involved in the 2009/10 Health Behaviour in
      School-aged Children (HBSC) study. Results of linear multilevel regression
      analyses indicate that adolescents in countries with relatively high levels of
      gender equality report higher life satisfaction than their peers in countries
      with lower levels of gender equality. The association between gender equality and
      adolescent life satisfaction remained significant after controlling for national
      wealth and income equality. It was equally strong for boys and girls. Moreover,
      the association between gender equality and life satisfaction was explained by
      social support in the family, peer and school context. This analysis suggests
      that gender equality fosters social support among members of a society, which in
      turn contributes to adolescent life satisfaction. Thus, promoting gender equality
      is likely to benefit all members of a society; not just by giving equal rights to
      women and girls, but also by fostering a supportive social climate for all.

PMID- 29019055
TI  - Psychological distress and coping strategies among women with incurable lung
      cancer: a qualitative study.
AB  - PURPOSE: Limited research has focused on women with lung cancer (LC) although
      they are recognized as the most vulnerable to psychological distress. This study
      explored in-depth the psychological distress experienced by women with incurable
      LC and analyzed the coping strategies with which they manage that distress.
      METHODS: A qualitative methodology with in-depth interviews was employed for 34
      women with advanced or recurrent LC. An inductive data-driven thematic analysis
      was applied to analyze transcripts. RESULTS: Psychological distress was an
      iterative process for the women. Four themes were identified: shock regarding the
      diagnosis, distress regarding cancer treatment and its side effects, the facing
      of a recurrent or progressive disease, and persistent struggle with the life
      limiting disease. Various coping strategies applied by the women to manage
      psychological distress were grouped into four themes: relying upon social
      support, focusing on positive thoughts, avoidance-based strategies, and religious
      faith and acceptance. CONCLUSIONS: Women with incurable LC experienced
      substantial iterative psychological distress throughout the illness, regardless
      of length of illness at time of interview. They applied multiple forms of coping.
      The findings enrich the limited existing literature on this understudied
      population and provide direction for the future development of interventions to
      improve their psychological well-being.

PMID- 29019057
TI  - Duplication of Yq- and proximal Yp-arms with deletion of almost all PAR1
      (including SHOX) in a young man with non-obstructive azoospermia, short stature
      and skeletal defects.
AB  - Duplications of Yq arm (and AZF) seems to be tolerated by fertile males, while
      mutations, deletions, duplications or haploinsufficiency of SHOX can originate a
      wide range of phenotypes, including short stature and skeletal abnormalities. We
      report a case of non-obstructive azoospermia in a young man with short stature,
      skeletal anomalies, normal intelligence and hormonal parameters. This male showed
      a very singular Y-chromosome aberration, consisting of a duplication of Yq and
      proximal regions of Yp, with a deletion of almost all PAR1 in Yptel, including
      SHOX. CBA- and RBA-banding and FISH-mapping with telomeric, centromeric, AZF and
      SHOX probes were used. These results were confirmed by array CGH, which revealed
      the following karyotype constitution: arr [hg19] Xp22.33 or Yp11.32p11.31
      (310,932-2,646,815 or 260,932-2,596,815) *1, Yp11.2q12 (8,641,183-59,335,913) *2.
      We conclude that the haploinsufficience of SHOX may be the cause of short stature
      and skeletal defects in the patient, while the non-obstructive azoospermia could
      be related to the lack of X-Y pairing during meiosis originated by the anomalous
      configuration of this chromosome abnormality and large deletion which occurred in
      Yp-PAR1.

PMID- 29019058
TI  - Devices of Responsibility: Over a Decade of Responsible Research and Innovation
      Initiatives for Nanotechnologies.
AB  - Responsible research and innovation (RRI) has come to represent a change in the
      relationship between science, technology and society. With origins in the
      democratisation of science, and the inclusion of ethical and societal aspects in
      research and development activities, RRI offers a means of integrating society
      and the research and innovation communities. In this article, we frame RRI
      activities through the lens of layers of science and technology governance as a
      means of characterising the context in which the RRI activity is positioned and
      the goal of those actors promoting the RRI activities in shaping overall
      governance patterns. RRI began to emerge during a time of considerable
      deliberation about the societal and governance challenges around nanotechnology,
      in which stakeholders were looking for new ways of integrating notions of
      responsibility in nanotechnology research and development. For this reason, this
      article focuses on nanotechnology as the site for exploring the evolution and
      growth of RRI.

PMID- 29019059
TI  - Systematical Investigation of Different Drug Nanocrystal Technologies to Produce
      Fast Dissolving Meloxicam Tablets.
AB  - Three different methods, i.e., high-pressure homogenization, wet bead milling,
      and a combination approach of freeze-drying and high-pressure homogenization,
      were used to produce meloxicam nanosuspensions, respectively. Wet bead milling
      led to the nanosuspensions with smallest particle size (88 nm) after 4 h and
      optimal dissolution performances. Freeze-dried meloxicam powder could highly
      improve the size reduction efficiency compared to the unmodified drug and
      particle size of the freeze-dried sample could be reduced to 342 nm after only
      one homogenization cycle at 1000 bar. The polymorphism transition and change of
      the particle morphology after the lyophilization might be important reasons to
      affect the nanosizing processes. Interestingly, the tablets prepared by using
      nanosuspensions from homogenizer and combination process showed faster
      dissolution in the first 20 min than the bead milling nanocrystal tablets.

PMID- 29019056
TI  - Physical Exercise Modulates L-DOPA-Regulated Molecular Pathways in the MPTP Mouse
      Model of Parkinson's Disease.
AB  - Parkinson's disease (PD) is characterized by the degeneration of dopaminergic
      (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in motor and
      non-motor dysfunction. Physical exercise improves these symptoms in PD patients.
      To explore the molecular mechanisms underlying the beneficial effects of physical
      exercise, we exposed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP)
      treated mice to a four-week physical exercise regimen, and subsequently explored
      their motor performance and the transcriptome of multiple PD-linked brain areas.
      MPTP reduced the number of DA neurons in the SNpc, whereas physical exercise
      improved beam walking, rotarod performance, and motor behavior in the open field.
      Further, enrichment analyses of the RNA-sequencing data revealed that in the MPTP
      treated mice physical exercise predominantly modulated signaling cascades that
      are regulated by the top upstream regulators L-DOPA, RICTOR, CREB1, or
      bicuculline/dalfampridine, associated with movement disorders, mitochondrial
      dysfunction, and epilepsy-related processes. To elucidate the molecular pathways
      underlying these cascades, we integrated the proteins encoded by the exercise
      induced differentially expressed mRNAs for each of the upstream regulators into a
      molecular landscape, for multiple key brain areas. Most notable was the opposite
      effect of physical exercise compared to previously reported effects of L-DOPA on
      the expression of mRNAs in the SN and the ventromedial striatum that are involved
      in-among other processes-circadian rhythm and signaling involving DA,
      neuropeptides, and endocannabinoids. Altogether, our findings suggest that
      physical exercise can improve motor function in PD and may, at the same time,
      counteract L-DOPA-mediated molecular mechanisms. Further, we hypothesize that
      physical exercise has the potential to improve non-motor symptoms of PD, some of
      which may be the result of (chronic) L-DOPA use.

PMID- 29019060
TI  - Reports of three cases with the initial presentation of mesenteric vasculitis in
      children with system lupus erythematous.
AB  - We reviewed three cases of systemic lupus erythematosus (SLE) in children with
      mesenteric vasculitis (LMV) as initial presentation and analysed their clinical
      characteristics to improve the understanding of this disease. Three patients with
      SLE were admitted to our hospital and initially presented with gastrointestinal
      symptoms. We retrospectively analysed their clinical data, including clinical
      presentations, laboratory results, images and short- and long-term treatment
      outcomes. (1) All three children were school-age girls. The patients were
      presented to our hospital with vomiting and abdominal pain as initial symptoms.
      The patients also had urinary symptoms, including proteinuria in three cases,
      ureteropelvic dilatation in two cases and hydronephrosis in one case. (2) The
      patients had various positive autoantibodies and a low complement level. Two of
      the patients had blood system involvement, and one had central nervous system
      symptoms. (3) All of the patients had active SLE (SLEDAI-2K score >= 5 points and
      moderate to severe degree 10-24). (4) Abdominal CT scans with contrast showed the
      'target sign' of the intestinal wall in case 1, a slightly thickened intestinal
      wall and blurry mesentery in case 2, and the 'comb sign' of the margin mesenteric
      blood vessels in case 3. (5) All three patients responded promptly to steroid
      therapy. The patients' symptoms improved rapidly after treatment. LMV is a rare
      SLE complication. The lack of comprehensive understanding of LMV's clinical
      presentation makes it considerably challenging to diagnose. LMV is also a serious
      complication of SLE that is often accompanied by concurrent damage to other
      organs. LMV often occurs with active SLE but responds rapidly to glucocorticoid
      therapy. Therefore, in order to make early diagnosis and treatment, we suggest
      checking autoantibodies and abdominal CT scans with contrast when children
      present with gastrointestinal symptoms and the involvement of other organs,
      especially the urinary system.

PMID- 29019062
TI  - Adding metyrapone to chemotherapy plus mitotane for Cushing's syndrome due to
      advanced adrenocortical carcinoma.

PMID- 29019061
TI  - Neuropsychological Measures that Predict Progression from Mild Cognitive
      Impairment to Alzheimer's type dementia in Older Adults: a Systematic Review and
      Meta-Analysis.
AB  - This study aimed to determine the extent to which cognitive measures can predict
      progression from mild cognitive impairment (MCI) to Alzheimer's type dementia
      (AD), assess the predictive accuracy of different cognitive domain categories,
      and determine whether accuracy varies as a function of age and length of follow
      up. We systematically reviewed and meta-analyzed data from longitudinal studies
      reporting sensitivity and specificity values for neuropsychological tests to
      identify individuals with MCI who will develop AD. We searched articles in
      Medline, Cochrane, EMBASE, PsycINFO, and the Web of Science. Methodological
      quality was assessed using the STARDem and QUADAS standards. Twenty-eight studies
      met the eligibility criteria (2365 participants) and reported predictive values
      from 61 neuropsychological tests with a 31-month mean follow-up. Values were
      pooled to provide combined accuracy for 14 cognitive domains. Many domains showed
      very good predictive accuracy with high sensitivity and specificity values (>=
      0.7). Verbal memory measures and many language tests yielded very high predictive
      accuracy. Other domains (e.g., executive functions, visual memory) showed better
      specificity than sensitivity. Predictive accuracy was highest when combining
      memory measures with a small set of other domains or when relying on broad
      cognitive batteries. Cognitive tests are excellent at predicting MCI individuals
      who will progress to dementia and should be a critical component of any toolkit
      intended to identify AD at the pre-dementia stage. Some tasks are remarkable as
      early indicators, whereas others might be used to suggest imminent progression.

PMID- 29019063
TI  - Statin Prescribing in the Elderly: Special Considerations.
AB  - PURPOSE OF REVIEW: Our aim was to examine the current evidence behind prescribing
      statins to individuals over 65 years of age with emphasis on those older than 75.
      Individuals over 75 years of age may often have multiple comorbidities and take
      many medications. Additionally, they are often underrepresented in randomized
      controlled trials (RCTs) of statins in older populations. While results of RCTs
      demonstrate the benefit of statin therapy in both primary and secondary
      prevention patients, clinicians must more carefully consider adverse effects and
      drug-drug interactions before prescribing statin therapy as well as determining
      the intensity in older individuals. RECENT FINDINGS: Four primary prevention
      trials support statins for primary prevention following a clinician-patient risk
      discussion. Of these, JUPITER and HOPE-3 studied participants 70 years of age and
      over who derived benefit. However, in those over 85 years, available information
      is inadequate to guide decisions regarding statin therapy. Documented statin
      adverse effects include new onset diabetes, myopathy, and medication
      interactions. Although cognitive decline has been reported anecdotally, its
      incidence was comparable to placebo in two RCTs with validated cognitive
      evaluations. Concerns about significant liver and kidney injury with statins were
      not corroborated in RCTs. For most patients, the potential for reducing ASCVD
      risk outweighs possible adverse effects; however, in the elderly, the impact of
      drug treatment on cognition, musculoskeletal ability, and independence must be
      heavily weighed. Given the limited high quality evidence for primary prevention
      in individuals over 75 years of age, neither the ACC-AHA nor USPSTF cholesterol
      guidelines recommend statin therapy for primary prevention in this patient
      population. If prescribed, physician judgment and shared decision-making are
      crucial. To aid clinicians, imaging studies of subclinical atherosclerosis may
      improve specificity of statin therapy to prevent ASCVD in the elderly in primary
      prevention.

PMID- 29019065
TI  - Correction to: Segregation of a novel p.(Ser270Tyr) MAF mutation and p.(Tyr56*)
      CRYGD variant in a family with dominantly inherited congenital cataracts.
AB  - There was a spacing error in the initial online publication, and there were
      errors in the Acknowledgments section. The original article has been updated.

PMID- 29019064
TI  - Inhibition in aging: What is preserved? What declines? A meta-analysis.
AB  - Aging has been assumed to go along with deficient inhibitory processes in
      cognitive performance. According to this inhibition deficit hypothesis, older
      adults are less able to suppress or ignore irrelevant thoughts and actions than
      young adults are. This hypothesis has been investigated in a large number of
      studies. We conducted a meta-analysis to determine whether there is an inhibition
      deficit in older age and whether this deficit is general or task-specific. We
      selected 176 studies in which young and older adults were tested on tasks
      commonly assumed to measure inhibition (i.e., the color Stroop, flanker, Simon,
      stop-signal, go/no-go, global-local, positive and negative compatibility tasks,
      as well as the paradigm assessing n-2 repetition costs in task switching). For
      most tasks (i.e., the color Stroop, flanker, and local tasks, as well as the n-2
      repetition costs), the results speak against an inhibition deficit in older age.
      Only in a few tasks (i.e., the go/no-go and stop-signal tasks), older adults
      showed impaired inhibition. Moreover, for four tasks (i.e., the Simon, global,
      positive and negative compatibility tasks), the results suggest that more studies
      are necessary to draw a firm conclusion. Together, the present findings call into
      question the hypothesis of a general inhibition deficit in older age.

PMID- 29019067
TI  - A novel mode of stimulating platelet formation activity in megakaryocytes with
      peanut skin extract.
AB  - We report in this study novel biochemical activities of peanut skin extract
      (PEXT) on thrombocytopoiesis. Peanut skin, derived from Arachis hypogaea L., is a
      traditional Chinese medicine that is used to treat chronic hemorrhage. We have
      shown that oral administration of PEXT increases the peripheral platelet levels
      in mice. Recently, we reported a liquid culture system that is useful for
      investigating megakaryocytopoiesis and thrombocytopoiesis from human CD34+ cells.
      In this liquid culture system, PEXT was shown to enhance the formation of
      CD41+/DAPI- cells (platelets), but had no effect on the formation of CD41+/DAPI+
      cells (megakaryocytes) or on the DNA content. Furthermore, PEXT selectively
      stimulated proplatelet formation from cultured mature megakaryocytes and phorbol
      12-myristate 13 acetate (PMA)-induced formation of platelet-like particles from
      Meg01 cells. Despite having no influence on the formation of megakaryocyte colony
      forming units (CFUs), PEXT increased the size of megakaryocytes during their
      development from CD34+ cells. PEXT showed no effect on the GATA-1 and NF-E2 mRNA
      levels, which are known to play an important role in thrombocytopoiesis and,
      based on the results of a pMARE-Luc (pGL3-MARE-luciferase) assay, had no
      influence on NF-E2 activation in Meg01 cells. These results suggest that PEXT
      accelerates proplatelet formation from megakaryocytes but does not influence the
      development of hematopoietic stem cells into megakaryocytes.

PMID- 29019066
TI  - Release Mechanism Between Ion Osmotic Pressure and Drug Release in Ionic-Driven
      Osmotic Pump Tablets (I).
AB  - The objective of this study was to develop an authentic ionic-driven osmotic pump
      system and investigate the release mechanism, simultaneously exploring the in
      vitro and in vivo correlation of the ionic-driven osmotic pump tablet. A
      comparison of the ionic-driven and conventional theophylline osmotic pump, the
      influence of pH and the amount of sodium chloride on drug release, the
      relationship between the ionic osmotic pressure and the drug release, and the
      pharmacokinetics experiment in beagle dogs were investigated. Consequently, the
      similarity factor (f 2 ) between the novel and conventional theophylline osmotic
      pump tablet was 60.18, which indicated a similar drug-release behavior. Also, the
      release profile fitted a zero-order kinetic model. The relative bioavailability
      of the ionic-driven osmotic pump to the conventional osmotic pump calculated from
      the AUC (0-infinity) was 93.6% and the coefficient (R = 0.9945) confirmed that
      the ionic-driven osmotic pump exhibited excellent IVIVC. The driving power of the
      ionic-driven osmotic pump was produced only by ions, which was strongly dependent
      on the ion strength, and a novel formula for the ionic-driven osmotic pump was
      derived which indicated that the drug-release rate was proportional to the ionic
      osmotic pressure and the sodium chloride concentration. Significantly, the
      formula can predict the drug-release rate and release characteristics of
      theophylline ionic-driven osmotic pumps, guiding future modification of the ionic
      osmotic pump.

PMID- 29019068
TI  - Early epithelial complications of accelerated trans-epithelial corneal
      crosslinking in treatment of keratoconus: a case series.
AB  - BACKGROUND: To report a case series of early postoperative complications
      following combined accelerated corneal crosslinking (CXL) and trans-epithelial
      technique in keratoconus. CASE PRESENTATIONS: Eleven eyes underwent accelerated
      trans-epithelial CXL (18 mW/cm2 for 5 min). Seven eyes (64%) developed
      complications in the first week postoperatively. Five eyes had large epithelial
      defects, and two eyes were complicated with diffuse punctate epithelial erosions.
      Early transient stromal haze was seen in eyes with epithelial complications.
      Anterior segment optical coherence tomography showed a faint demarcation line in
      six eyes (55%) with epithelial complications. CONCLUSION: A significant number of
      eyes developed epithelial complications shortly after combined accelerated trans
      epithelial CXL, which defeated the benefits of leaving the epithelium intact.

PMID- 29019069
TI  - PRO-CON debate: valve sparing aortic root surgery. PRO: reimplantation.
AB  - The remodeling and the reimplantation procedures were described more than 25
      years ago with the aim of sparing, otherwise normal aortic valve in the presence
      of a root aneurysm. Because of its ability to reconstruct the sinuses of
      Valsalva, the remodeling procedure was considered to be more physiological than
      the reimplantation. However, because the remodeling lacked annular stabilization,
      the long-term stability of the procedure was questioned. However, through the
      years, both procedures have been significantly improved, so that is now possible
      to perform a reimplantation procedure with neo-sinuses reconstruction or a
      remodeling procedure with annular stabilization. In this way, both procedures can
      now guarantee an anatomical root reconstruction and an increased long-term
      durability. Today preference for a reimplantation procedure is based on the
      perception of a better reproducibility of the surgical procedure, an increased
      procedural safety due to the characteristic hemostatic feature of this surgical
      approach, and to a much larger amount of data present in the literature on long
      term results.

PMID- 29019070
TI  - Time-Dependent Production of Endothelium-Related Biomarkers is Affected
      Differently in Hemorrhagic and Septic Shocks.
AB  - Shock is associated with inflammation-induced endothelial dysfunction. The aim of
      this study was to determine time-dependent alteration of blood biomarkers related
      to endothelial function in hemorrhagic and septic shocks. Hemorrhagic shock was
      induced by bleeding the animals. A cecal ligation and incision model was used to
      induce septicemia. Resuscitation was carried out by infusion of lactated Ringer's
      solution. Resuscitation extended survival time in both shock groups. Blood
      pressure increased by resuscitation in the hemorrhagic shock but not in the
      septic shock. While hemorrhage caused a decrease in plasma levels of nitric oxide
      (NO) and hydrogen sulfide (H2S), asymmetric dimethylarginine (ADMA) and total
      antioxidant capacity (TAC) levels were increased. Only NO and TAC levels at the
      late phase were reversed by resuscitation. On the other hand, plasma levels of
      NO, ADMA, and TAC were increased by septicemia and resuscitation did not alter
      the septicemia-induced increase. These results indicate that blood biomarkers
      related to endothelial function were differentially affected by hemorrhage and
      septicemia. The time scale of biomarker production should be taken into
      consideration for the diagnostic and therapeutic approaches to these life
      threatening diseases.

PMID- 29019072
TI  - Mass spectrometry-based metabolomics to identify taurine-modified metabolites in
      heart.
AB  - Taurine is an abundant beta-amino acid found in high concentration in mammalian
      tissues. Taurine possesses many beneficial functions in mammalian cells. There
      are also a variety of taurine-conjugated products formed between taurine and bile
      acids, fatty acids, chloramine, mitochondrial tRNA, etc., and some of these have
      been identified as functional compounds. In the present study, we identified
      taurine-conjugated metabolites using LC-MS-based metabolome analysis of heart
      extracts prepared from hearts of wild-type and taurine transporter-knockout
      (TauTKO) mice, the latter being severely taurine deficient. Comparison analysis
      of metabolites identified taurine-containing dipeptides, including
      glutamyltaurine, aspartyltaurine, isoleucyltaurine, and leucyltaurine, which are
      present in wild-type but not TauTKO hearts. Acyltaurines (taurine-conjugated
      fatty acids) and taurine-conjugated bile acids were also detected, with levels
      unchanged in the TauTKO heart in comparison to the wild-type heart. These results
      demonstrate that taurine exists not only in the standard free form within the
      heart, but also in multiple conjugated forms, whose functions in the heart remain
      to be discovered.

PMID- 29019074
TI  - In vitro Inhibitory Effect of Gymnema sylvestre Extracts and Total Gymnemic Acids
      Fraction on Select Cytochrome P450 Activities in Rat Liver Microsomes.
AB  - BACKGROUND AND OBJECTIVES: Gymnema sylvestre R. Br. is a well-known Indian
      medicinal herb. Gymnemic acids are pentacyclic triterpenes saponins and active
      phytoconstituents of Gymnema sylvestre. The study aimed at evaluation of the in
      vitro rat liver cytochrome P450 (CYP) inhibition potential of extracts and total
      gymnemic acid (TA)-enriched fractions from G. sylvestre. METHODS: Standardization
      of G. sylvestre [ethanolic (EL), hydroethanolic (HE), total acid of ethanolic
      (TAE), total acid of hydroethanolic (TAHE) and total acid of aqueous (TAAQ)
      extract] was done with respect to deacyl gymnemic acid (DAGA), using reverse
      phase-high performance liquid chromatography (RP-HPLC). Total triterpenoid
      content was determined by vanillin perchloric acid assay. RESULTS: Total
      triterpene content was found to be the highest in TAAQ (59.86 +/- 0.005% w/w) and
      TAE (49.77 +/- 0.009% w/w). TAAQ showed IC50 <= 50 ug/ml for all selected CYP
      activities. Testosterone 6beta-hydroxylation was strongly inhibited by TAE (IC50:
      15.48 +/- 2.13 ug/ml) and was moderately by TAAQ and EL with IC50 >= 50 ug/ml.
      Flurbiprofen 4'-hydroxylation was subject to strong, weak and moderate inhibition
      by TAAQ (IC50: 34.67 +/- 1.38 ug/ml), TAE (IC50: >= 50 ug/ml) and EL (IC50: > 50
      ug/ml), respectively. Dextromethorphan O-demethylation was inhibited by TAHE and
      TAAQ. CONCLUSIONS: In vitro inhibition studies suggested that TA strongly
      inhibits activity of selected CYP. This inhibition may possibly be due to
      triterpenoids and gymnemic acids that have been reported to be present in it.
      Data also suggest a potential for possible in vivo herb-drug interactions
      involving G. sylvestre and other medications that are metabolized by the same
      CYP.

PMID- 29019075
TI  - Efficient Malic Acid Production in Escherichia coli Using a Synthetic Scaffold
      Protein Complex.
AB  - Recently, malic acid has gained attention due to its potential application in
      food, pharmaceutical, and medical industries. In this study, the synthetic
      scaffold complex strategy was employed between the two key enzymes pyruvate
      kinase (PykF) and malic enzyme (SfcA); SH3 ligand was attached to PykF, and the
      SH3 domain was attached to the C-terminus of ScfA. Synthetic scaffold systems can
      organize enzymes spatially and temporally to increase the local concentration of
      intermediates. In a flask culture, the recombinant strain harboring scaffold
      complex produced a maximum concentration of 5.72 g/L malic acid from 10 g/L
      glucose. The malic acid production was significantly increased 2.1-fold from the
      initial culture period. Finally, malic acid production was elevated to 30.2 g in
      a 5 L bioreactor from recombinant strain XL-1 blue.

PMID- 29019073
TI  - Cholecalciferol-PEG Conjugate Based Nanomicelles of Doxorubicin for Treatment of
      Triple-Negative Breast Cancer.
AB  - Triple-negative breast cancer (TNBC) is the leading cancer in women.
      Chemotherapeutic agents used for TNBC are mainly associated with dose-dependent
      toxicities and development of resistance. Hence, novel strategies to overcome
      resistance and to offer dose reduction are warranted. In this study, we designed
      a novel dual-functioning agent, conjugate of cholecalciferol with PEG2000
      (PEGCCF) which can self-assemble into micelles to encapsulate doxorubicin (DOX)
      and act as a chemosensitizer to improve the therapeutic potential of DOX. DOX
      loaded PEGCCF (PEGCCF-DOX) micelles have particle size, polydispersity index
      (PDI), and zeta potential of 40 +/- 8.7 nm, 0.180 +/- 0.051, and 2.39 +/- 0.157
      mV, respectively. Cellular accumulation studies confirmed that PEGCCF was able to
      concentration-dependently enhance the cellular accumulation of DOX and rhodamine
      123 in MDA-MB-231 cells through its P-glycoprotein (P-gp) inhibition activity.
      PEGCCF-DOX exhibited 1.8-, 1.5-, and 2.9-fold enhancement in cytotoxicity of DOX
      in MDA-MB-231, MDA-MB-468, and MDA-MB-231DR (DOX-resistant) cell lines,
      respectively. Western blot analyses showed that PEGCCF-DOX caused significant
      reduction in tumor markers including mTOR, c-Myc, and antiapoptotic marker Bcl-xl
      along with upregulation of preapoptotic marker Bax. Further, reduction in mTOR
      activity by PEGCCF-DOX indicates reduced P-gp activity due to P-gp downregulation
      as well and, hence, PEGCCF causes enhanced chemosensitization and induces
      apoptosis. Substantially enhanced apoptotic activity of DOX (10-fold) in MDA-MB
      231(DR) cells confirmed apoptotic potential of PEGCCF. Conclusively, PEGCCF
      nanomicelles are promising delivery systems for improving anticancer activity of
      DOX in TNBC, thereby reducing its side effects and may act as a potential carrier
      for other chemotherapeutic agents.

PMID- 29019076
TI  - Starting a Medical Technology Venture as a Young Academic Innovator or Student
      Entrepreneur.
AB  - Following the footprints of Bill Gates, Steve Jobs and Mark Zuckerberg, there has
      been a misconception that students are better off quitting their studies to bring
      to life their ideas, create jobs and monetize their inventions. Having
      historically transitioned from manpower to mind power, we live in one of the most
      rapidly changing times in human history. As a result, academic institutions that
      are supposed to be pioneers and educators of the next generations have started to
      realize that they need to adapt to a new system, and change their policies to be
      more flexible towards patent ownership and commercialization. There is an
      infrastructure being developed towards students starting their own businesses
      while continuing with their studies. This paper aims to provide an overview of
      the existing landscape, the exciting rewards as well as risks awaiting a student
      entrepreneur, the challenges of the present ecosystem, and questions to consider
      prior to embarking on such a journey. Various entities influencing the start-up
      environment are considered, specifically for the medical technology sector. These
      parties include but are not limited to: scientists, clinicians, investors,
      academic institutions and governments. A special focus will be set on the
      seemingly unbridgeable gap between founding a company and a scientific career.

PMID- 29019078
TI  - Chitosan-Zn Chelate Downregulates TLR4-NF-kappaB Signal Pathway of Inflammatory
      Response and Cell Death-Associated Proteins Compared to Inorganic Zinc.
AB  - The study was conducted to investigate the effect of chitosan-zinc chelate (CS
      Zn) on TLR4-NF-kappaB signaling pathway and cell death-associated proteins in a
      weanling pig model. A total of 90 weaned piglets were allotted to three dietary
      treatments (the dietary treatments were as follows: (1) experimental diet with
      supplemental ZnSO4 (150 mg Zn/kg diet), (2) experimental diet with supplemental
      CS-Zn (150 mg Zn/kg diet), and (3) experimental diet with a supplemental mixture
      of chitosan and ZnSO4 (150 mg/kg Zn; the content of chitosan was equal to CS-Zn,
      which is according to molar basis)). The feeding trial lasted 30 days. The
      results showed that compared with ZnSO4 or CS+ZnSO4, CS-Zn decreased the
      expressions of the cell death-associated proteins Beclin-1, and Cleaved-Caspase3
      and the ratio of LC3II/LC3I. The intestinal expressions of TLR4 and its
      downstream signals NF-kappaB, IKKbeta, and IkappaBalpha were down-regulated
      simultaneously. Moreover, the contents of pro-inflammatory cytokines IL-2, TNF
      alpha, and IFN-gamma were decreased. The results indicated that as organic zinc
      source, CS-Zn was more effective than ZnSO4 and the mixture of chitosan and ZnSO4
      for inhibiting inflammatory response and decreasing the expressions of proteins
      associated with cell death. The great anti-inflammatory effect of CS-Zn was
      modulated by inhibiting the TLR4-NF-kappaB signaling pathway, and the effect of
      CS-Zn on down-regulating the expression of cell death-associated proteins might
      also closely be associated with the TLR4-NF-kappaB signaling pathway.

PMID- 29019077
TI  - Halophilic viruses with varying biochemical and biophysical properties are
      amenable to purification with asymmetrical flow field-flow fractionation.
AB  - Viruses come in various shapes and sizes, and a number of viruses originate from
      extremities, e.g. high salinity or elevated temperature. One challenge for
      studying extreme viruses is to find efficient purification conditions where
      viruses maintain their infectivity. Asymmetrical flow field-flow fractionation
      (AF4) is a gentle native chromatography-like technique for size-based separation.
      It does not have solid stationary phase and the mobile phase composition is
      readily adjustable according to the sample needs. Due to the high separation
      power of specimens up to 50 um, AF4 is suitable for virus purification. Here, we
      applied AF4 for extremophilic viruses representing four morphotypes: lemon
      shaped, tailed and tailless icosahedral, as well as pleomorphic enveloped. AF4
      was applied to input samples of different purity: crude supernatants of infected
      cultures, polyethylene glycol-precipitated viruses and viruses purified by
      ultracentrifugation. All four virus morphotypes were successfully purified by
      AF4. AF4 purification of culture supernatants or polyethylene glycol-precipitated
      viruses yielded high recoveries, and the purities were comparable to those
      obtained by the multistep ultracentrifugation purification methods. In addition,
      we also demonstrate that AF4 is a rapid monitoring tool for virus production in
      slowly growing host cells living in extreme conditions.

PMID- 29019080
TI  - Influence of the internal anatomy on the leakage of root canals filled with
      thermoplastic technique.
AB  - OBJECTIVES: The aim of this paper is to evaluate the influence of the internal
      anatomy on the leakage of root canals filled with the thermoplastic technique.
      MATERIALS AND METHODS: The upper central incisors (UCI) and mesial roots of the
      lower molars (MRLM) (n = 12 each) were tested regarding leakage using the gas
      enhanced permeation test (GEPT) after root filling. The quality of the root
      fillings was assessed using micro-computed tomography (MUCT) by superimposing
      scans before and after treatment to calculate unfilled volume. The calculated
      void volume was compared between the groups and correlated to the measured
      leakage values. Data were analyzed using t test and Pearson's correlation tests
      (p < 0.05). RESULTS: The mean void volume did not differ between UCI and MRLM
      (13.7 +/- 6.2% vs. 14.2 +/- 6.8%, respectively). However, significantly more
      leakage was evident in the MRLM (p < 0.001). While the leakage correlated highly
      to the void volume in the MRLM group (R 2 = 0.981, p < 0.001), no correlation was
      found in UCI (R 2 = 0.467, p = 0.126). CONCLUSION: MRLM showed higher leakage
      values, which correlated to the void volume in the root canal fillings. CLINICAL
      RELEVANCE: Care should always be taken while doing root canal treatments, but
      attention to teeth with known/expected complex root canal anatomy should be
      considered.

PMID- 29019079
TI  - Pharmacotherapy Choice Is Associated with 2-Year Mortality for Patients with
      Heart Failure and Reduced Ejection Fraction.
AB  - INTRODUCTION: Factors associated with mortality for patients with heart failure
      and reduced ejection fraction (HFrEF) are known; however, the association between
      initial pharmacotherapy (IPT) and mortality is unclear in real-world settings.
      METHODS: Using a retrospective design and claims database, 14,359 Medicare
      patients with HFrEF from August 2010 to July 2015 were identified. Index date was
      first HF claim. IPT was mono- or combo-angiotensin-converting enzyme inhibitor
      (ACEI), angiotensin II receptor blocker (ARB), beta-blocker (BB), hydralazine
      nitrate (HN), and aldosterone antagonist (AA) within 1 year post-index. A
      multivariable time-dependent Cox model estimated associations between IPT and 2
      year all-cause mortality. RESULTS: Patients' median age was 76 (70-82) years;
      45.1% were female. Within 1 month post-index, 61.4% had IPT, 6.1% started after
      the first month, and 32.4% had no IPT in the first year. Of IPTs, 47.5% were mono
      vasodilators (ACEI, ARB or HN), 23.3% mono-vasodilator + BB, 16.9% mono-BB, and
      3.5% triple therapy [(ACEI or ARB) + BB + (HN or AA)]. Two-year mortality rate
      was 27.9%. Compared to mono-vasodilator therapy, patients initiating triple
      therapy had 29.3% lower risk of 2-year mortality; those on mono-BB or no IPT had
      higher mortality risk. CONCLUSION: IPT was associated with decreased 2-year
      mortality risk. Timely consideration of triple IPT therapies may be warranted
      once HFrEF diagnosis is confirmed. FUNDING: Novartis Pharmaceuticals Corp.
      located in East Hanover, NJ, USA.

PMID- 29019081
TI  - Modification of NK cell subset repartition and functions in granulocyte colony
      stimulating factor-mobilized leukapheresis after expansion with IL-15.
AB  - The ability of natural killer (NK) cells to kill tumor cells without antigen
      recognition makes them appealing as an adoptive immunotherapy. However, NK cells
      are not routinely used in the context of leukemic relapse after hematopoietic
      stem cell transplantation. Patients who experience relapse can be treated with
      donor lymphocyte infusions (DLI) based on small-cell fractions frozen at the time
      of transplantation. Since peripheral blood stem cells (PBSCs) are increasingly
      used as a stem cell source and as a source of cells for DLI, we aimed to evaluate
      the impact of G-SCF mobilization on NK cell phenotype, subset repartition, and
      functionality. Immunomagnetically isolated NK cells from healthy donor blood,
      donor PBSCs, and patient PBSCs were expanded for 14 days with IL-15. The
      expansion capacity, phenotype, and functions (cytokine secretion and
      cytotoxicity) of NK cell subsets based on CD56 and CD16 expression were then
      evaluated. Mobilized sources showed a significant decrease of CD56brightCD16+ NK
      cells (28 versus 74%), whereas a significant increase (64 versus 15%) of
      CD56brightCD16- NK cells was observed in comparison with peripheral blood.
      Patient-mobilized NK cells showed a significantly decreased cytotoxicity, and
      antibody-dependent cell cytototoxicity (ADCC) was also observed to a lesser
      extent in NK cells from healthy donor PBSC. G-CSF-mobilized NK cell TNF-alpha and
      IFN-gamma secretion was impaired at day 0 compared to healthy donors but was
      progressively restored after culture. In conclusion, expansion of NK cells from G
      CSF-mobilized sources may progressively improve their functionality.

PMID- 29019082
TI  - Loss of the nutrient sensor TAS1R3 leads to reduced bone resorption.
AB  - The taste receptor type 1 (TAS1R) family of heterotrimeric G protein-coupled
      receptors participates in monitoring energy and nutrient status. TAS1R member 3
      (TAS1R3) is a bi-functional protein that recognizes amino acids such as L-glycine
      and L-glutamate or sweet molecules such as sucrose and fructose when dimerized
      with TAS1R member 1 (TAS1R1) or TAS1R member 2 (TAS1R2), respectively. It was
      recently reported that deletion of TAS1R3 expression in Tas1R3 mutant mice leads
      to increased cortical bone mass but the underlying cellular mechanism leading to
      this phenotype remains unclear. Here, we independently corroborate the increased
      thickness of cortical bone in femurs of 20-week-old male Tas1R3 mutant mice and
      confirm that Tas1R3 is expressed in the bone environment. Tas1R3 is expressed in
      undifferentiated bone marrow stromal cells (BMSCs) in vitro and its expression is
      maintained during BMP2-induced osteogenic differentiation. However, levels of the
      bone formation marker procollagen type I N-terminal propeptide (PINP) are
      unchanged in the serum of 20-week-old Tas1R3 mutant mice as compared to controls.
      In contrast, levels of the bone resorption marker collagen type I C-telopeptide
      are reduced greater than 60% in Tas1R3 mutant mice. Consistent with this, Tas1R3
      and its putative signaling partner Tas1R2 are expressed in primary osteoclasts
      and their expression levels positively correlate with differentiation status.
      Collectively, these findings suggest that high bone mass in Tas1R3 mutant mice is
      due to uncoupled bone remodeling with reduced osteoclast function and provide
      rationale for future experiments examining the cell-type-dependent role for TAS1R
      family members in nutrient sensing in postnatal bone remodeling.

PMID- 29019084
TI  - A Flexible Bayesian Model for Estimating Subnational Mortality.
AB  - Reliable subnational mortality estimates are essential in the study of health
      inequalities within a country. One of the difficulties in producing such
      estimates is the presence of small populations among which the stochastic
      variation in death counts is relatively high, and thus the underlying mortality
      levels are unclear. We present a Bayesian hierarchical model to estimate
      mortality at the subnational level. The model builds on characteristic age
      patterns in mortality curves, which are constructed using principal components
      from a set of reference mortality curves. Information on mortality rates are
      pooled across geographic space and are smoothed over time. Testing of the model
      shows reasonable estimates and uncertainty levels when it is applied both to
      simulated data that mimic U.S. counties and to real data for French departements.
      The model estimates have direct applications to the study of subregional health
      patterns and disparities.

PMID- 29019083
TI  - Microbial Stability of Pharmaceutical and Cosmetic Products.
AB  - This review gives a brief overview about microbial contamination in
      pharmaceutical products. We discuss the distribution and potential sources of
      microorganisms in different areas, ranging from manufacturing sites, pharmacy
      stores, hospitals, to the post-market phase. We also discuss the factors that
      affect microbial contamination in popular dosage forms (e.g., tablets, sterile
      products, cosmetics). When these products are contaminated, the microorganisms
      can cause changes. The effects range from mild changes (e.g., discoloration,
      texture alteration) to severe effects (e.g., changes in activities, toxicity).
      The most common method for countering microbial contamination is the use of
      preservatives. We review some frequently used preservatives, and we describe the
      mechanisms by which microorganisms develop resistance to these preservatives.
      Finally, because preservatives are inherently toxic, we review the efforts of
      researchers to utilize water activity and other non-preservative approaches to
      combat microbial contamination.

PMID- 29019086
TI  - Family history influences the tumor characteristics and prognosis of breast
      cancers developing during postmenopausal hormone therapy.
AB  - Long term use of postmenopausal hormone therapy (HT) has been reported to
      increase breast cancer risk. On the other hand, observational studies suggest
      that breast cancers diagnosed during HT may have a more favorable prognosis.
      While family history is a risk factor for breast cancer, and genetic factors also
      influence prognosis, the role of family history in combination with HT use has
      been little studied. We investigated the relationship between HT, family history,
      and prognosis in 584 (267 exposed) familial and 952 (460 exposed) non-familial
      breast cancer cases, using three survival end points: death from breast cancer
      (BCS), distant disease free survival (DDFS), and local recurrence free survival
      (LRFS). Among non-familial cases, HT was associated with better BCS (HR 0.63, 95%
      CI 0.41-0.94; p = 0.025), and DDFS (HR 0.58, 95% CI 0.40-0.85; p = 0.005), with a
      consistent but not statistically significant effect in LRFS. This effect was not
      seen in familial cases (HR > 1.0), and family history was found to interact with
      HT in BCS (p(interaction) = 0.0067) (BC-death) and DDFS (p(interaction) =
      0.0070). There was phenotypic heterogeneity between HT-associated tumors in
      familial and non-familial cases, particularly on estrogen receptor (ER) status,
      although the interaction between HT and family history appears to be at least
      partially independent of these markers (p = 0.0370 after adjustment for standard
      prognostic factors). If confirmed by further studies, our results suggest that
      family history should be taken into consideration in clinical counseling before
      beginning a HT regimen.

PMID- 29019085
TI  - The Arnon-Buchanan cycle: a retrospective, 1966-2016.
AB  - For the first decade following its description in 1954, the Calvin-Benson cycle
      was considered the sole pathway of autotrophic CO2 assimilation. In the early
      1960s, experiments with fermentative bacteria uncovered reactions that challenged
      this concept. Ferredoxin was found to donate electrons directly for the reductive
      fixation of CO2 into alpha-keto acids via reactions considered irreversible.
      Thus, pyruvate and alpha-ketoglutarate could be synthesized from CO2, reduced
      ferredoxin and acetyl-CoA or succinyl-CoA, respectively. This work opened the
      door to the discovery that reduced ferredoxin could drive the Krebs citric acid
      cycle in reverse, converting the pathway from its historical role in carbohydrate
      breakdown to one fixing CO2. Originally uncovered in photosynthetic green sulfur
      bacteria, the Arnon-Buchanan cycle has since been divorced from light and shown
      to function in a variety of anaerobic chemoautotrophs. In this retrospective,
      colleagues who worked on the cycle at its inception in 1966 and those presently
      working in the field trace its development from a controversial reception to its
      present-day inclusion in textbooks. This pathway is now well established in major
      groups of chemoautotrophic bacteria, instead of the Calvin-Benson cycle, and is
      increasingly referred to as the Arnon-Buchanan cycle. In this retrospective,
      separate sections have been written by the authors indicated. Bob Buchanan wrote
      the abstract and the concluding comments.

PMID- 29019087
TI  - Influence of entomopathogenic fungus, Metarhizium anisopliae, alone and in
      combination with diatomaceous earth and thiamethoxam on mortality, progeny
      production, mycosis, and sporulation of the stored grain insect pests.
AB  - The stored grain insects cause great damage to grains under storage conditions.
      Synthetic insecticides and fumigants are considered as key measures to control
      these stored grain insect pests. However, the major issue with these chemicals is
      grain contamination with chemical residues and development of resistance by
      insect pests to these chemicals. Biological control is considered as a potential
      alternative to chemical control especially with the use of pathogens, alone or in
      combination with selective insecticides. The present study was conducted to
      evaluate the synergism of Metarhizium anisopliae with diatomaceous earth (DE) and
      thiamethoxam against four insect pests on the stored wheat grains. In the first
      bioassay, the M. anisopliae was applied at 1.4 * 104 and 1.4 * 106conidia/ml
      alone and in integration with two concentrations (250 and 500 ppm) of tested DE.
      The tested fungus when combined with DE and thiamethoxam possessed synergistic
      impact as compared to their individual efficacy. Adult mortality increased with
      respect to increased exposure interval and doses. In the second bioassay, M.
      anisopliae was applied at 1.4 * 104 conidia/ml individually and in combination
      with three concentrations (0.50, 0.75, and 1.00 ppm) of thiamethoxam. Results
      concluded that M. anisopliae integrated with DE and thiamethoxam provides more
      effective control of stored grain insect pests.

PMID- 29019088
TI  - Involvement of mitochondrial pathway in environmental metal pollutant lead
      induced apoptosis of chicken liver: perspectives from oxidative stress and energy
      metabolism.
AB  - This study aimed to investigate the possible mechanisms of environmental metal
      pollutant lead (Pb)-induced apoptosis in chicken. Forty 8-day-old healthy
      chickens were randomly assigned to two groups (n = 20/group) after raising
      standard commercial diet and drinking water for 1 week: including control group
      and Pb group ((CH3COO)2Pb 350 mg/L of drinking water); the chickens were given
      euthanasia and collected livers at 90 days. A significant increase of apoptosis
      rate were found in Pb group and Pb induced obvious ultrastructural changes of
      chicken liver. The mRNA levels of glycometabolism key enzymes were significantly
      lower in Pb group than those in controls. Higher levels of malondialdehyde (MDA)
      and nitric oxide (NO) were observed in Pb group; the activities of antioxidant
      enzymes and ATPases were significantly lower in Pb group than those in controls,
      while the inducible nitric oxide synthase (iNOS) activity was on the contrary.
      The mRNA and protein levels of pro-apoptotic genes were all lower in Pb group
      than those in controls. Altogether, Pb-induced mitochondrial swelling and nuclear
      chromatin condensation, oxidative stress, energy metabolism disorder, thereby
      lead to apoptosis via mitochondrial pathway in chicken liver, suggesting that Pb
      induced mitochondrial pathway apoptosis plays an important role in the mechanisms
      of Pb cytotoxicity to chicken liver.

PMID- 29019090
TI  - Resuscitation on the pitch.

PMID- 29019089
TI  - Exercise and the Cortisol Awakening Response: A Systematic Review.
AB  - BACKGROUND: The cortisol awakening response (CAR) has been used as a biomarker of
      stress response in a multitude of psychological investigations. While a myriad of
      biochemical responses have been proposed to monitor responses to exercise
      training, the use of CAR within the exercise and sports sciences is currently
      limited and is a potentially underutilized variable. Therefore, the purpose of
      this review was to collate studies that incorporate both exercise and CAR, in an
      effort to better understand (a) whether CAR is a useful marker for monitoring
      exercise stress and (b) how CAR may be most appropriately used in future
      research. METHODS: A systematic review of the literature was conducted, following
      PRISMA guidelines. Searches were conducted using PubMed, SportDISCUS, Scopus, and
      PsychInfo databases, using search terms related toCAR and exercise and physical
      activity. RESULTS: 10,292 articles were identified in the initial search, with 32
      studies included in the final analysis. No studies investigated the effects of
      laboratory-controlled exercise on CAR. Variable effects were observed, possibly
      due to inconsistencies in study design, methodology, population, and CAR
      analysis. The available literature suggests a threshold of exercise may be
      required to alter the HPA axis and affect CAR. Moreover, CAR may represent a
      combination of previous exercise load and upcoming stress, making current
      interpretation of field-based observational research challenging. CONCLUSIONS:
      More research is needed to fully elucidate the influence of exercise on CAR and
      address a number of gaps in the literature, including controlling exercise load,
      consistent sample collection, and CAR calculation and analysis.

PMID- 29019092
TI  - Rapid Detection of Human Norovirus in Frozen Raspberries.
AB  - Raspberries have lately caused several human norovirus (HuNoV) outbreaks in
      Europe. In this study, we developed and evaluated for HuNoV reverse transcription
      (RT)-PCR detection in frozen raspberries extraction methods that have equal
      sensitivity but are less time-consuming than widely used methods based on
      polyethylene glycol (PEG) precipitation and chloroform-butanol purification. One
      method was applied to stored frozen raspberries linked to previous HuNoV
      outbreaks and berries on sale. In the virus elution-based Method 1, sparkling
      water eluted viruses most efficiently from the berries. Method 2, based on direct
      nucleic acid extraction with minor PEG supplement, yielded the highest number of
      positive findings (4 out of 9) at low virus concentration level of 100 genome
      copies HuNoV genogroup II per 25 g raspberries. Both methods showed approximately
      equal sensitivity to a method including PEG precipitation and chloroform-butanol
      purification. Two naturally contaminated berry samples linked to HuNoV outbreaks
      in 2006 and 2009 were still positive for HuNoV genogroup I, but all berry
      products purchased from a local store remained negative for HuNoV. In conclusion,
      this study presents two efficient and rapid methods which can be used in urgent
      HuNoV outbreak investigations, since the results of the virus analysis are
      available in a few hours.

PMID- 29019091
TI  - Preventive and Therapeutic Effects of Thymol in a Lipopolysaccharide-Induced
      Acute Lung Injury Mice Model.
AB  - Acute lung injury (ALI) is a life-threatening syndrome which causes a high
      mortality rate worldwide. In traditional medicine, lots of aromatic plants-such
      as some Thymus species-are used for treatment of various lung diseases including
      pertussis, bronchitis, and asthma. Thymol, one of the primary active constituent
      derived from Thymus vulgaris (thyme), has been reported to exhibit potent anti
      microbial, anti-oxidant, and anti-inflammatory activities in vivo and in vitro.
      The present study aims to investigate the protective effects of thymol in
      lipopolysaccharide (LPS)-induced lung injury mice model. In LPS-challenged mice,
      treatment with thymol (100 mg/kg) before or after LPS challenge significantly
      improved pathological changes in lung tissues. Thymol also inhibited the LPS
      induced inflammatory cells influx, TNF-alpha and IL-6 releases, and protein
      concentration in bronchoalveolar lavage fluid (BALF). Additionally, thymol
      markedly inhibited LPS-induced elevation of MDA and MPO levels, as well as
      reduction of SOD activity. Further study demonstrated that thymol effectively
      inhibited the NF-kappaB activation in the lung. Taken together, these results
      suggested that thymol might be useful in the therapy of acute lung injury.

PMID- 29019093
TI  - Triptans and CGRP blockade - impact on the cranial vasculature.
AB  - The trigeminovascular system plays a key role in the pathophysiology of migraine.
      The activation of the trigeminovascular system causes release of various
      neurotransmitters and neuropeptides, including serotonin and calcitonin gene
      related peptide (CGRP), which modulate pain transmission and vascular tone.
      Thirty years after discovery of agonists for serotonin 5-HT1B and 5-HT1D
      receptors (triptans) and less than fifteen after the proof of concept of the
      gepant class of CGRP receptor antagonists, we are still a long way from
      understanding their precise site and mode of action in migraine. The effect on
      cranial vasculature is relevant, because all specific anti-migraine drugs and
      migraine pharmacological triggers may act in perivascular space. This review
      reports the effects of triptans and CGRP blocking molecules on cranial
      vasculature in humans, focusing on their specific relevance to migraine
      treatment.

PMID- 29019096
TI  - Two-stage mixotrophic cultivation for enhancing the biomass and lipid
      productivity of Chlorella vulgaris.
AB  - This study proposes a two-stage mixotrophic process for cultivating Chlorella
      vulgaris. Heterotrophic growth is the dominant step in Phase I (to increase
      microalgal biomass) and photoautotrophic growth occurs in Phase II (to improve
      biomass concentration and lipid production). The results show that the addition
      of the low-cost antioxidant sodium erythorbate (8 g L-1) significantly
      accelerates the growth of microalgae in the first stage with air aeration.
      Furthermore, a higher CO2 fixation rate was obtained in the second stage (at
      least 344.32 mg CO2 L-1 day-1) with 10% CO2 aeration. This approximately
      corresponds to an increase of 177% over simple photoautotrophic cultivation with
      10% CO2 aeration during the whole period. The two-stage cultivation strategy
      achieved a maximum C. vulgaris biomass concentration of 3.45 g L-1 and lipid
      productivity of 43.70 mg L-1 day-1, which are 1.85 and 1.64 times those arising
      due to simple photoautotrophy, respectively. Moreover, an analysis of the
      product's fatty acid profile indicates that C. vulgaris might be an ideal
      candidate for two-stage mixotrophic cultivation of a renewable biomass for use in
      biodiesel applications. Another interesting point to note from the study is that
      it is an insufficiency of N and CO2 that probably limits the further growth of C.
      vulgaris.

PMID- 29019094
TI  - Lipid droplet-associated gene expression and chromatin remodelling in LIPASE 5'
      upstream region from beginning- to mid-endodormant bud in 'Fuji' apple.
AB  - KEY MESSAGE: We found that lipid accumulation in the meristem region and the
      expression of MdLIP2A, which appears to be regulated by chromatin remodeling,
      coincided with endodormancy induction in the 'Fuji' apple. In deciduous trees,
      including apples (Malus * domestica Borkh.), lipid accumulation in the meristem
      region towards endodormancy induction has been thought to be an important process
      for the acquisition of cold tolerance. In this study, we conducted histological
      staining of crude lipids in the meristem region of 'Fuji' apples and found that
      lipid accumulation coincided with endodormancy induction. Since a major component
      of lipid bodies (triacylglycerol) is esterified fatty acids, we analysed fatty
      acid-derived volatile compounds and genes encoding fatty acid-modifying enzymes
      (MdLOX1A and MdHPL2A); the reduction of lipid breakdown also coincided with
      endodormancy induction. We then characterised the expression patterns of lipid
      body-regulatory genes MdOLE1 and MdLIP2A during endodormancy induction and found
      that the expression of MdLIP2A correlated well with lipid accumulation towards
      endodormancy induction. Based on these results, we conducted chromatin
      remodelling studies and localized the cis-element in the 5'-upstream region of
      MdLIP2A to clarify its regulatory mechanism. Finally, we revealed that chromatin
      was concentrated - 764 to - 862 bp of the 5'-upstream region of MdLIP2A, which
      harbours the GARE [gibberellin responsive MYB transcription factor binding site]
      and CArG [MADS-box transcription factor binding site] motifs-meristem development
      related protein-binding sites.

PMID- 29019097
TI  - Efficacy of Conventional and Liposomal Povidone-Iodine in Infected Mesh Skin
      Grafts: An Exploratory Study.
AB  - INTRODUCTION: Infection is a major threat to wound healing and a leading cause of
      graft loss in patients undergoing meshed skin grafts (MSGs). Therefore, topical
      antisepsis is important in the overall treatment scheme. METHODS: An exploratory
      satellite group of 14 patients with infected MSGs were enrolled as part of a
      prospective, randomized, controlled, parallel-group, open-label, pilot Phase II
      study that investigated the efficacy and tolerability of 3% liposomal povidone
      iodine hydrogel (PVP-ILH, Repithel(r); RepiGel(r)) versus chlorhexidine gauze in
      non-infected MSGs. The satellite group included both patients with infected wound
      beds prior to grafting and patients with infection of a previously placed graft,
      with MSG sizes ranging from 50 to 1000 cm2, who were randomized to treatment with
      (PVP-ILH) or 10% povidone-iodine ointment (Betaisodona(r); BETADINE(r)).
      Medication was applied in a 2-mm layer and dressing changes with identical
      application of study medication took place daily. Wounds were evaluated by
      photoplanimetry, microbiologically and subjectively by patients and physicians.
      RESULTS: The results for the main study group have been reported previously. In
      the satellite group, both PVP-ILH and povidone-iodine ointment performed
      remarkably well with respect to lowering the bacterial count and restoring wound
      healing, with different emphasis. Povidone-iodine ointment showed excellent
      antibacterial efficacy with no detectable microorganisms by Day 10, and rapid re
      epithelialization (mean 90% by Day 6). PVP-ILH also demonstrated rapid re
      epithelialization (mean 72% by Day 6) with a trend towards improved subjective
      measures of wound healing quality. Four patients (40%) receiving PVP-ILH
      experienced partial graft loss (10-15% of total MSG area); no patients in the
      povidone-iodine ointment group experienced graft loss. CONCLUSION: Our results
      suggest that povidone-iodine ointment has a strong role in managing infected
      wounds, especially when a high concentration of povidone-iodine may be warranted,
      while PVP-ILH indicated similar beneficial results on markers of wound healing
      quality in larger infected wounds. TRIAL REGISTRATION: The trial was conducted
      prior to mandatory registration of drug products, PVP-ILH represents a medicated
      device in the EU and many other countries. FUNDING: Mundipharma Research GmbH &
      Co. KG.

PMID- 29019095
TI  - Cost-effectiveness of surveillance and prevention strategies in BRCA1/2 mutation
      carriers.
AB  - BACKGROUND: Cost-effectiveness analysis is an important aspect of healthcare,
      including in Japan, where preventive measures for BRCA1/2 mutation carriers are
      not covered by health insurance. METHODS: We developed Markov models in a
      simulated cohort of women aged 35-70 years, and compared outcomes of surveillance
      with risk-reducing mastectomy (RRM) at age 35, risk-reducing salpingo
      oophorectomy (RRSO) at age 45, and both (RRM&RRSO). We used breast and ovarian
      cancer incidences and adverse event rates from the previous studies, adjuvant
      chemotherapy, and hormonal therapy rates from the Hereditary Breast and Ovarian
      Cancer Registration 2015 in Japan, mortality rates from the National Cancer
      Center Hospital, Japan Society of Clinical Oncology, and Ministry of Health,
      Labour and Welfare, and direct costs from St. Luke's International Hospital and
      Keio University Hospital. We used previously published preference ratings of
      women without known high risk to adjust survival for quality of life. The
      discount rate was 2%. RESULTS: Compared with surveillance, RRSO and RRM&RRSO were
      dominant (both cost-saving and more effective), and RRM was cost-effective in
      BRCA1 mutation carriers, while RRM and RRM&RRSO were dominant and RRSO was cost
      effective in BRCA2. Among the four strategies including surveillance, RRM&RRSO
      and RRM were the most cost-effective in BRCA1 and BRCA2 mutation carriers,
      respectively. CONCLUSIONS: With quality adjustment, RRM, RRSO, and RRM&RRSO were
      all cost-effective preventive strategies in BRCA1/2 mutation carriers, with
      RRM&RRSO being the most cost-effective in BRCA1 and RRM in BRCA2. This result
      supports the inclusion of insurance coverage for BRCA mutation carriers in Japan.

PMID- 29019098
TI  - Gallstone ileus: monocentric experience looking for the adequate approach.
AB  - Common complications of biliary lithiasis are cholecystitis, bile duct lithiasis,
      and acute biliary pancreatitis. Gallstone ileus is uncommon complications often
      requiring surgical approach. It is a mechanical bowel obstruction caused by a
      biliary calculus usually originating from a bilioenteric fistula. Because of the
      limited number of reported cases, the optimal surgical method of treatment has
      been the subject of ongoing debate. A retrospective, observational, descriptive
      study was conduct on patients diagnosed with non-neoplastic bowel occlusion. For
      each case of gallstone ileus, the following variables were revised: personal and
      clinical data, mean time of onset of symptoms, length of pre- and postoperative
      stay, imaging studies, biochemical tests, site of the bilioenteric fistula and
      occlusion, surgical strategy, postoperative course, follow-up, and mortality. Of
      the 290 cases of non-neoplastic bowel obstruction from 2008 to 2015, 11 (3.7%)
      were due to gallstone ileus. The majority of patients were elderly women (F 9/M
      2) with high average age (82.4; 76-88) and significant comorbidities. Five cases
      of small-bowel occlusions were treated with solely enterolithotomy. For the
      remaining six cases, digestive resection and cholecystectomy were performed.
      Complications rate (20 vs. 80%) and postoperative stay (12.4 vs. 25.3 days) were
      lower in the group of enterolithotomy with respect to the group treated with
      other procedures. In-hospital mortality was nil. Gallstone ileus is an uncommon
      bowel occlusion affecting mainly the elderly female population. Enterotomy with
      stone extraction alone is associated with better outcomes than more invasive
      techniques.

PMID- 29019099
TI  - Formulation and Pharmacokinetics of HSA-core and PLGA-shell Nanoparticles for
      Delivering Gemcitabine.
AB  - Gemcitabine-loaded core-shell nanoparticles (CSNPs), comprised of a cross-linked
      HSA-core and PLGA-shell, were prepared through a modified double emulsification
      method, and the processing parameters were systematically investigated. The
      optimized CSNPs had a particle size of 241 +/- 36.2 nm and an encapsulation
      efficiency of 41.52%. The core-shell structure was characterized by optical
      microscope (OM), scanning electron microscopy (SEM), and transmission electron
      microscopy (TEM). The amorphous nature of the encapsulated drug was confirmed by
      differential scanning calorimetry (DSC) and X-ray diffraction (XRD). An in vitro
      release study demonstrated that the CSNPs had an improved sustained release
      profile controlled by erosion of materials in combination with drug diffusion. In
      vivo pharmacokinetics of CSNPs obtained a bigger area under concentration-time
      curve (AUC), t 1/2, and C max compared to free drug solution. The results suggest
      that HSA-PLGA-based CSNPs can be a promising carrier for the sustained release of
      gemcitabine.

PMID- 29019101
TI  - Oxytocin and Human Sensitive and Protective Parenting.
AB  - In this chapter we review the evidence for the role of oxytocin in parenting, and
      discuss some crucial but outstanding questions. This is not meant to be a
      comprehensive review of all studies on oxytocin and parenting in general.
      Instead, special attention will be paid to a dimension of parenting that has been
      largely neglected in behavioral and neurobiological research on parental
      caregiving, namely protection. Parental protection has received considerable
      attention in animal research but, despite its evolutionary importance, not in
      studies on humans. It is argued that oxytocin may have specific significance for
      the protective dimension of parenting. The effects of exogenous oxytocin may be
      dependent not only on contextual factors, but also on personal characteristics,
      most notably gender, on endogenous levels of oxytocin, and on early childhood
      experiences. Examining the contextual, personal, hormonal, neural, genetic, and
      behavioral mechanisms of protective parenting in tandem is essential for the
      development of a comprehensive theory of protective parenting, and for the
      identification of "biomarkers" for insensitive and unprotective parenting that
      should be taken into account in preventive parenting interventions.

PMID- 29019100
TI  - Oxytocin and Social Cognition.
AB  - Oxytocin has been linked to many domains within the realm of "social cognition."
      For example, research has shown that oxytocin affects trusting behavior,
      cooperation, as well as the perception and processing of facial expressions.
      Furthermore, oxytocin increases empathy and seems to exert differential effects
      on in-group versus out-group preferences. However, there are some conflicting
      results that point towards a modulatory effect of oxytocin, depending on a
      variety of contextual and within-subject factors. Research about the underlying
      mechanisms (e.g., neural circuits and genetics) indicates that the modulation of
      amygdala activity by oxytocin is elementary for the understanding of social
      cognitive processes. As regards genetics, several variants of the oxytocin
      receptor gene (OXTR) have been extensively studied in relation to social
      cognition. Taken together, oxytocin is an important modulator of social cognitive
      processes, although substantially more research is needed in order to understand
      the complexity of oxytocinergic effects on social perception, cognition, and
      interpersonal behavior.

PMID- 29019102
TI  - Calcium-sensing receptor polymorphisms increase the risk of osteoporosis in
      ageing males.

PMID- 29019103
TI  - Tip of the Tongue States Increase Under Evaluative Observation.
AB  - We tested the frequent assumption that the difficulty of word retrieval increases
      when a speaker is being observed and evaluated. We modified the Trier Social
      Stress Test (TSST) so that participants believed that its evaluative observation
      components continued throughout the duration of a subsequent word retrieval task,
      and measured participants' reported tip of the tongue (TOT) states. Participants
      in this TSST condition experienced more TOTs than participants in a comparable,
      placebo TSST condition in which there was no suggestion of evaluative
      observation. This experiment provides initial evidence confirming the assumption
      that evaluative observation by a third party can be disruptive to word retrieval.
      We interpret our findings by proposing an extension to a well-supported
      theoretical model of TOTs.

PMID- 29019104
TI  - The Effect of Boron on Some Biochemical Parameters in Experimental Diabetic Rats.
AB  - In this study, we evaluated the effect of boron (B) as boric acid (BA) on body
      weight (b.w.); blood glucose; plasma insulin; lipase and paraoxonase (PON1)
      activities; and serum triglyceride, total cholesterol, high-density lipoprotein
      (HDL) and low-density lipoprotein (LDL) cholesterol, lipid peroxidation (MDA),
      and total antioxidant capacity (TAC) in streptozotocin (STZ)-induced experimental
      diabetes in rats. Sixty Wistar albino rats (200-250 g) were divided into six
      groups of ten. The groups received the following treatment: group 1, control
      group; group 2, 50 mg/kg (b.w.) i.p. STZ-induced diabetes; group 3, 5 mg/kg
      (b.w.) B; group 4, 10 mg/kg (b.w.) B; group 5, diabetes + 5 mg/kg (b.w.) B; and
      group 6, diabetes + 10 mg/kg (b.w.) B. The experiment lasted 4 weeks. Increased
      serum MDA levels with diabetes were significantly reduced and although it is not
      statistically significant, serum TAC levels approached to values of control
      group; also, insignificant increases were observed in HDL cholesterol levels in
      experimental diabetic rats with treatment 5 and 10 mg/kg B. Furthermore, body
      weight, plasma insulin, and lipase activities increased insignificantly, blood
      glucose and serum LDL cholesterol decreased significantly, and total cholesterol
      levels decreased insignificantly in the diabetes + 10 mg/kg B group. There was no
      difference between the groups in terms of plasma PON1 activities and serum
      triglyceride levels. In conclusion, B may have beneficial effects on some
      biochemical parameters changes in experimental diabetes, and in order to
      determine the full effect of this element on the metabolism, further studies are
      required which use various dosages and compounds of B.

PMID- 29019105
TI  - Symmetries Constrain Dynamics in a Family of Balanced Neural Networks.
AB  - We examine a family of random firing-rate neural networks in which we enforce the
      neurobiological constraint of Dale's Law-each neuron makes either excitatory or
      inhibitory connections onto its post-synaptic targets. We find that this
      constrained system may be described as a perturbation from a system with
      nontrivial symmetries. We analyze the symmetric system using the tools of
      equivariant bifurcation theory and demonstrate that the symmetry-implied
      structures remain evident in the perturbed system. In comparison, spectral
      characteristics of the network coupling matrix are relatively uninformative about
      the behavior of the constrained system.

PMID- 29019107
TI  - Erratum to: Durvalumab: First Global Approval.

PMID- 29019106
TI  - Antimicrobial Properties of Perfusate Fluid After Cytoreductive Surgery and
      Hyperthermic Intraperitoneal Chemotherapy (CS-HIPEC) with Mitomycin C.
AB  - BACKGROUND: Infectious postoperative complications often delay systemic
      chemotherapy after cytoreductive surgery and hyperthermic intraperitoneal
      chemotherapy (CS-HIPEC). Because the authors have empirically observed fewer
      incisional infectious complications than expected after CS-HIPEC with mitomycin C
      (MMC), they investigated the antimicrobial properties of HIPEC perfusate fluid.
      METHODS: This study prospectively measured in vitro bacterial growth inhibition
      by HIPEC perfusate (n = 18). After 10 uL of perfusate had been plated on agar
      plate inoculated by standard strains of either Escherichia coli (strain 25922) or
      Staphylococcus aureus (strain 25923), it was incubated at 37  degrees C for 24 h.
      Antimicrobial activity evidenced by a zone of complete growth inhibition was
      measured in millimeters. These were compared against growth inhibition produced
      by control groups represented by MMC solution in normal saline (MMC
      concentrations of 2, 4, 6, 8, and 8.75 ug/mL), 7 per group. RESULTS: Bacterial
      inhibition by HIPEC perfusate was stronger against E. coli than against S. aureus
      (13.1 +/- 6.8 vs 8.3 +/- 7.7 mm; p = 0.005). No E. coli inhibition was observed
      for MMC saline in concentrations of 2 through 8 ug/mL (p < 0.001 each), and
      inhibition of 4.5 +/- 5.7 mm was observed for an MMC saline concentration of 8.75
      ug/mL (p = 0.007). The S. aureus inhibition zones by MMC saline solutions were
      2.2 +/- 2.1 (p = 0.002), 5.1 +/- 2.3 (p = 0.135), 7.5 +/- 1.0 (p = 0.654), 9.6 +/
      0.9 (p = 0.058), and 10.2 +/- 0.4 mm (p = 0.021). CONCLUSION: The antimicrobial
      properties of HIPEC perfusate are considerable but variable between patients and
      stronger against E. coli than against S. aureus. Further studies of HIPEC carrier
      solutions and chemotherapy agents may result in reduction of surgical-site
      infection and thus enhanced patient recovery.

PMID- 29019108
TI  - Molecular modeling elucidates the cellular mechanism of synaptotagmin-SNARE
      inhibition: a novel plausible route to anti-wrinkle activity of botox-like
      cosmetic active molecules.
AB  - Synaptotagmin 1 (Syt1) is the Ca2+ sensor protein with an essential role in
      neurotransmitter release. Since the wrinkle formation is due to the excessive
      muscle fiber stimulation in the face, a helpful stratagem to diminish the wrinkle
      line intenseness is to weaken the innervating neuron activity through Syt1
      inhibition which is one of the possible therapeutic strategies against wrinkles.
      Recently, experimental evidence showed that botox-like peptides, which are
      typically used as SNARE modulators, may inhibit Syt1. In this work, we applied
      molecular modeling to (1) characterize the structural framework and (2) define
      the atomistic information of the factors for the inhibition mechanism. The
      modeling identified the plausible binding cleft able to efficiently bind all
      botox-like peptides. The MD simulations revealed that all peptides induced
      significant Syt1 rigidity by binding in the cleft of the C2A-C2B interface. The
      consequence of this binding event is the suppression of the protein motion
      associated with conformational change of Syt1 from the closed form to the open
      form. On this basis, this finding may therefore be of subservience for the
      advancement of novel botox-like molecules for the therapeutic treatment of
      wrinkle, targeting and modulating the function of Syt1.

PMID- 29019109
TI  - Automatic delineation of functional lung volumes with 68Ga-ventilation/perfusion
      PET/CT.
AB  - BACKGROUND: Functional volumes computed from 68Ga-ventilation/perfusion (V/Q)
      PET/CT, which we have shown to correlate with pulmonary function test parameters
      (PFTs), have potential diagnostic utility in a variety of clinical applications,
      including radiotherapy planning. An automatic segmentation method would
      facilitate delineation of such volumes. The aim of this study was to develop an
      automated threshold-based approach to delineate functional volumes that best
      correlates with manual delineation. Thirty lung cancer patients undergoing both
      V/Q PET/CT and PFTs were analyzed. Images were acquired following inhalation of
      Galligas and, subsequently, intravenous administration of 68Ga-macroaggreted
      albumin (MAA). Using visually defined manual contours as the reference standard,
      various cutoff values, expressed as a percentage of the maximal pixel value, were
      applied. The average volume difference and Dice similarity coefficient (DSC) were
      calculated, measuring the similarity of the automatic segmentation and the
      reference standard. Pearson's correlation was also calculated to compare
      automated volumes with manual volumes, and automated volumes optimized to PFT
      indices. RESULTS: For ventilation volumes, mean volume difference was lowest (-
      0.4%) using a 15%max threshold with Pearson's coefficient of 0.71. Applying this
      cutoff, median DSC was 0.93 (0.87-0.95). Nevertheless, limits of agreement in
      volume differences were large (- 31.0 and 30.2%) with differences ranging from -
      40.4 to + 33.0%. For perfusion volumes, mean volume difference was lowest and
      Pearson's coefficient was highest using a 15%max threshold (3.3% and 0.81,
      respectively). Applying this cutoff, median DSC was 0.93 (0.88-0.93).
      Nevertheless, limits of agreement were again large (- 21.1 and 27.8%) with volume
      differences ranging from - 18.6 to + 35.5%. Using the 15%max threshold, moderate
      correlation was demonstrated with FEV1/FVC (r = 0.48 and r = 0.46 for ventilation
      and perfusion images, respectively). No correlation was found between other PFT
      indices. CONCLUSIONS: To automatically delineate functional volumes with 68Ga-V/Q
      PET/CT, the most appropriate cutoff was 15%max for both ventilation and perfusion
      images. However, using this unique threshold systematically provided unacceptable
      variability compared to the reference volume and relatively poor correlation with
      PFT parameters. Accordingly, a visually adapted semi-automatic method is favored,
      enabling rapid and quantitative delineation of lung functional volumes with 68Ga
      V/Q PET/CT.

PMID- 29019112
TI  - Methodology in Aristotle's Theory of Spontaneous Generation.
AB  - Aristotle's theory of spontaneous generation offers many puzzles to those who
      wish to understand his theory both within the context of his biology and within
      the context of his more general philosophy of nature. In this paper, I approach
      the difficult and vague elements of Aristotle's account of spontaneous generation
      not as weaknesses, but as opportunities for an interesting glimpse into the
      thought of an early scientist struggling to reconcile evidence and theory. The
      paper has two goals: (1) to give as charitable and full an account as possible of
      what Aristotle's theory of spontaneous generation was, and to examine some of its
      consequences; and (2) to reflect on Aristotle as a scientist, and what his
      comments reveal about how he approached a difficult problem. In particular, I
      propose that the well-recognized problem of the incompatibility between
      Aristotle's concept of spontaneity and his theory of spontaneous generation
      presents an opportunity for insight into his scientific methodology when
      approaching ill-understood phenomena.

PMID- 29019110
TI  - Long-term laboratory culture causes contrasting shifts in tolerance to two marine
      pollutants in copepods of the genus Tigriopus.
AB  - Organismal chemical tolerance is often used to assess ecological risk and monitor
      water quality, yet tolerance can differ between field- and lab-raised organisms.
      In this study, we examined how tolerance to copper (Cu) and tributyltin oxide
      (TBTO) in two species of marine copepods, Tigriopus japonicus and T.
      californicus, changed across generations under benign laboratory culture (in the
      absence of pre-exposure to chemicals). Both copepod species exhibited similar
      chemical-specific changes in tolerance, with laboratory maintenance resulting in
      increased Cu tolerance and decreased TBTO tolerance. To assess potential factors
      underlying these patterns, chemical tolerance was measured in conjunction with
      candidate environmental variables (temperature, UV radiation, diet type, and
      starvation). The largest chemical-specific effect was found for starvation, which
      decreased TBTO tolerance but had no effect on Cu tolerance. Understanding how
      chemical-specific tolerance can change in the laboratory will be critical in
      strengthening bioassays and their applications for environmental protection and
      chemical management.

PMID- 29019111
TI  - Institutional Experience with Ostomies Created During Cytoreductive Surgery and
      Hyperthermic Intraperitoneal Chemoperfusion.
AB  - BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion
      (CRS-HIPEC) is a complex procedure that often requires ostomy creation to protect
      high-risk anastomoses. This study aimed to evaluate the authors' institutional
      experience with CRS-HIPEC-associated ostomies, determine predictors of ostomy
      creation and reversal, and assess their impact on survival. METHODS: The study
      analyzed clinicopathologic, perioperative, and oncologic data from a prospective
      database of 1435 CRS-HIPEC procedures for peritoneal metastases. The Kaplan-Meier
      method was used to estimate survival. Multivariate analyses identified
      associations with ostomy creation/reversal and survival. RESULTS: Ostomies were
      created in 34% of the patients, most commonly loop ileostomies (82%). Loop
      ileostomies were reversed in the majority of patients (83%), whereas non-loop
      ileostomies were infrequently reversed (< 10% reversal rate). In a multivariate
      logistic regression model, intermediate or high tumor grade,
      colectomy/proctectomy, longer operative time, and lower Charlson comorbidity
      index were associated with loop ileostomy creation, whereas incomplete
      macroscopic resection, colorectal histology, and major postoperative
      complications were associated with non-reversal of loop ileostomy. In a
      multivariate Cox proportional hazards model, intermediate or high tumor grade and
      non-reversal of loop ileostomy were associated with worse overall survival.
      CONCLUSIONS: Loop ileostomies were almost always reversed, whereas non-loop
      ileostomies were almost always permanent. Hospital readmissions for loop
      ileostomy-related complications were common. Therefore, formal outpatient
      protocols for prevention and management should be implemented. Non-reversal of
      loop ileostomy was associated with very poor survival.

PMID- 29019114
TI  - Looking Toward the Next Fifty Years at the Journal of the History of Biology.

PMID- 29019115
TI  - What Do Final Year Medical Students Understand by the Concept of Recovery? A
      Descriptive Qualitative Study.
AB  - OBJECTIVE: Traditional teaching in psychiatry does little to address recovery
      concepts. The aim of this study was to evaluate the incorporation of a recovery
      focused teaching program for medical students in psychiatry. METHODS: Recovery,
      as understood by medical students who had participated in a recovery-focused
      teaching program, was assessed by thematic analysis of recovery-focused
      assessment reflections. RESULTS: Six major themes emerged from the recovery
      reflections from final year medical students are as follows: (1) recovery as a
      person-centered approach, (2) the need for social integration, (3) non-diagnostic
      framing of mental illness, (4) tensions between the medical model and personal
      recovery, (5) a patient's willingness to engage with mental health services, and
      (6) the development of a positive sense of self. CONCLUSIONS: A recovery teaching
      program was associated with students expressing knowledge of recovery principles
      and positive attitudes towards people with experience of mental illness.
      Psychiatric placements for medical students may benefit from a recovery focus.

PMID- 29019116
TI  - Bulk Freeze-Drying Milling: a Versatile Method of Developing Highly Porous
      Cushioning Excipients for Compacted Multiple-Unit Pellet Systems (MUPS).
AB  - The compaction of multiple-unit pellet system (MUPS) is a challenging process due
      to the ease of coat damage under high compression pressure, thereby altering drug
      release rates. To overcome this, cushioning excipients are added to the tablet
      formulation. Excipients can be processed into pellets/granules and freeze-dried
      to increase their porosity and cushioning performance. However, successful
      formation of pellets/granules has specific requirements that limit formulation
      flexibility. In this study, a novel top-down approach that harnessed bulk freeze
      drying milling was explored to avoid the challenges of pelletization/granulation.
      Aqueous dispersions containing 20%, w/w hydroxypropyl methylcellulose (HPMC),
      partially pregelatinised starch or polyvinylpyrrolidone alone, and with lactose
      (Lac) in 1:1 ratio, were freeze-dried and then milled to obtain particulate
      excipients for characterization and evaluation of their cushioning performance.
      This study demonstrated that bulk freeze-drying milling is a versatile method for
      developing excipients that are porous and directly compressible. The freeze
      drying process modified the materials in a unique manner which could impart
      cushioning properties. Compared to unprocessed excipients, the freeze-dried
      products generally exhibited better cushioning effects. The drug release profile
      of drug-loaded pellets compacted with freeze-dried Lac-HPMC excipients was
      similar to that of the uncompacted drug-loaded pellets (f 2 value = 51.7),
      indicating excellent cushioning effects. It was proposed that the specific
      balance of brittle and plastic nature of the freeze-dried Lac-HPMC composite
      conferred greater protective effect to the drug-loaded pellets, making it
      advantageous as a cushioning excipient.

PMID- 29019119
TI  - "Total Mesenteric Peritonectomy for Peritoneal Metastases" (with Video) by Jean
      Baptiste Cazauran et al.

PMID- 29019118
TI  - Frailty Correlates with Postoperative Mortality and Major Morbidity After
      Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.
AB  - BACKGROUND: Frailty is increasingly being recognized as a powerful predictor of
      postoperative outcomes for cancer patients. This study examined the role of the
      modified frailty index (MFI) in predicting outcomes for patients undergoing
      cytoreduction (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC).
      METHODS: Data from National Surgical Quality Improvement Program (NSQIP) patients
      who underwent CRS/HIPEC between 2005 and 2014 were reviewed. The MFI, validated
      for use in NSQIP, was used to determine correlation between frailty and
      postoperative outcomes. RESULTS: The analysis included 1171 patients. The
      patients were divided into three groups: non-frail (MFI 0), mildly frail (MFI 1
      or 2), or severely frail (MFI >= 3). More than 90% of patients had an MFI of 0 or
      1. The MFI was 0 for 716 patients (61.1%), 1 for 373 patients (31.9%), 2 for 76
      patients (6.5%), 3 for 5 patients (0.4%), and 4 for 1 patient (0.1%). Overall,
      grade 4 Clavien morbidity was observed in 99 patients (8.5%) and mortality in 26
      patients (2.2%). For non-frail, mildly frail, and severely frail patients,
      worsening frailty correlated respectively with increases in grade 4 Clavien
      morbidity (6.7% vs. 10.9% vs. 33.3%; p = 0.004) and mortality (1.3% vs. 3.3% vs.
      33.3%; p < 0.001). In the multivariate analysis, which included age of 70 years
      or older and albumin level of 3 or lower, frailty was the only factor that
      correlated with postoperative mortality: non-frail:reference, mildly frail [odds
      ratio (OR) 2.76, 95% confidence interval (CI) 1.14-6.73; p = 0.025], severely
      frail (OR 29.1, 95% CI 4-210.87; p = 0.01), age of 70 years or older (OR 1.16,
      95% CI 0.34-3.93; p = 0.81), and albumin level of 3 or lower (OR 2.42, 95% CI
      0.84-6.98; p = 0.1). CONCLUSIONS: Frailty is a strong predictor of major grade 4
      morbidity and mortality after CRS/HIPEC. Severe frailty should be a relative
      contraindication to CRS/HIPEC. Frailty correlates should be a selection factor in
      the evaluation of all candidates for CRS/HIPEC.

PMID- 29019120
TI  - Two-Dimensional Gel Electrophoresis and 2D-DIGE.
AB  - Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) continues to be one
      of the most versatile and widely used techniques to study the proteome of a
      biological system. In particular, a modified version of 2D-PAGE, two-dimensional
      difference gel electrophoresis (2D-DIGE), which uses differential labeling of
      protein samples with up to three fluorescent tags, offers greater sensitivity and
      reproducibility over conventional 2D-PAGE gels for differential quantitative
      analysis of protein expression between experimental groups. Both these methods
      have distinct advantages in the separation and identification of thousands of
      individual proteins species including protein isoforms and post-translational
      modifications. This review will discuss the principles of 2D-PAGE and 2D-DIGE
      including limitations to the methods. 2D-PAGE and 2D-DIGE continue to be popular
      methods in bioprocessing-related research (particularly on recombinant Chinese
      hamster ovary cells), which will also be discussed in the review chapter.

PMID- 29019121
TI  - Comparative DIGE Proteomics.
AB  - Gel-based proteomics has been widely used for the systematic cataloging of the
      protein constituents of defined biofluids, purified organelles, individual cell
      types, heterogeneous tissues and isolated organs, as well as being applied to
      comparative biochemical and biomedical analyses of complex biological specimens.
      Of the many electrophoretic techniques used in modern biochemical approaches,
      large-scale protein separation by difference gel electrophoresis (DIGE) has
      established itself as the most powerful analytical tool in comparative
      proteomics. Both 2-dye and 3-dye fluorescence systems with minimal or saturation
      labeling are routinely used. This chapter briefly describes the technical
      advantages of the pre-electrophoretic fluorescent labeling technique and
      discusses the bioanalytical usefulness of this highly successful electrophoretic
      method.

PMID- 29019122
TI  - 2D-DIGE and Fluorescence Image Analysis.
AB  - 2D-DIGE is still a very widespread technique in proteomics for the identification
      of panels of biomarkers, allowing to tackle with some important drawback of
      classical two-dimensional gel-electrophoresis. However, once 2D-gels are
      obtained, they must undergo a quite articulated multistep image analysis
      procedure before the final differential analysis via statistical mono- and
      multivariate methods. Here, the main steps of image analysis software are
      described and the most recent procedures reported in the literature are briefly
      presented.

PMID- 29019117
TI  - Physiologically Based Pharmacokinetic Modeling of Transporter-Mediated Hepatic
      Clearance and Liver Partitioning of OATP and OCT Substrates in Cynomolgus
      Monkeys.
AB  - In the present investigations, we evaluate in vitro hepatocyte uptake and
      partitioning for the prediction of in vivo clearance and liver partitioning.
      Monkeys were intravenously co-dosed with rosuvastatin and bosentan, substrates of
      the organic anion transporting polypeptides (OATPs), and metformin, a substrate
      of organic cation transporter 1 (OCT1). Serial plasma and liver samples were
      collected over time. Liver and plasma unbound fraction was determined using
      equilibrium dialysis. In vivo unbound partitioning (Kpu,u) for rosuvastatin,
      bosentan, and metformin, calculated from total concentrations in the liver and
      plasma, were 243, 553, and 15, respectively. A physiologically based
      pharmacokinetic monkey model that incorporates active and passive hepatic uptake
      was developed to fit plasma and liver concentrations. In addition, a two
      compartment model was used to fit in vitro hepatic uptake curves in suspended
      monkey hepatocyte to determine active uptake, passive diffusion, and
      intracellular unbound fraction parameters. At steady-state in the model, in vitro
      Kpu,u was determined. The results demonstrated that in vitro values under
      predicted in vivo active uptake for rosuvastatin, bosentan, and metformin by 6.7
      , 28-, and 1.5-fold, respectively, while passive diffusion was over-predicted. In
      vivo Kpu,u values were under-predicted from in vitro data by 30-, 79-, and 3
      fold. In conclusion, active uptake and liver partitioning in monkeys for OATP
      substrates were greatly under-predicted from in vitro hepatocyte uptake, while
      OCT-mediated uptake and partitioning scaled reasonably well from in vitro,
      demonstrating substrate- and transporter-dependent scaling factors. The
      combination of in vitro experimental and modeling approaches proved useful for
      assessing prediction of in vivo intracellular partitioning.

PMID- 29019123
TI  - DIGE Analysis Software and Protein Identification Approaches.
AB  - DIGE is a high-resolution two-dimensional gel electrophoresis method, with
      excellent dynamic range obtained by fluorescent tag labeling of protein samples.
      Scanned images of DIGE gels show thousands of protein spots, each spot
      representing a single or a group of protein isoforms. By using commercially
      available software, each protein spot is defined by an outline, which is
      digitized and correlated with the quantity of proteins present in each spot.
      Software packages include DeCyder, SameSpots, and Dymension 3. In addition,
      proteins of interest can be excised from post-stained gels and identified with
      conventional mass spectrometry techniques. High-throughput mass spectrometry is
      performed using sophisticated instrumentation including matrix-assisted laser
      desorption ionization time-of-flight (MALDI-TOF), MALDI-TOF/TOF, and liquid
      chromatography tandem mass spectrometry (LC-MS/MS). Tandem MS (MALDI-TOF/TOF or
      LC-MS/MS), analyzes fragmented peptides, resulting in amino acid sequence
      information, especially useful when protein spots are low abundant or where a
      mixture of proteins is present.

PMID- 29019124
TI  - Native DIGE: Efficient Tool to Elucidate Protein Interactomes.
AB  - Protein-protein interactions and multi-protein assemblies are inherent features
      of proteomes, involving soluble and membrane proteins. This imparts structural
      and functional heterogeneity to the proteome. One needs to consider this aspect
      while studying changes in abundance or activities of proteins in response to any
      physiological stimulus. Abundance changes in components of a given proteome can
      be best visualized and quantified using electrophoresis-based approaches. Here,
      we describe the method of Blue Native Difference Gel Electrophoresis (BN DIGE) to
      quantify abundance changes in proteins in the context of protein-protein
      interactions. This method confers an additional advantage to monitor quantitative
      changes in membrane proteins, which otherwise is a difficult task.

PMID- 29019125
TI  - Comparative Two-Dimensional Fluorescence Gel Electrophoresis.
AB  - Two-dimensional comparative fluorescence gel electrophoresis (CoFGE) uses an
      internal standard to increase the reproducibility of coordinate assignment for
      protein spots visualized on 2D polyacrylamide gels. This is particularly
      important for samples, which need to be compared without the availability of
      replicates and thus cannot be studied using differential gel electrophoresis
      (DIGE). CoFGE corrects for gel-to-gel variability by co-running with the sample
      proteome a standardized marker grid of 80-100 nodes, which is formed by a set of
      purified proteins. Differentiation of reference and analyte is possible by the
      use of two fluorescent dyes. Variations in the y-dimension (molecular weight) are
      corrected by the marker grid. For the optional control of the x-dimension (pI),
      azo dyes can be used. Experiments are possible in both vertical and horizontal
      (h) electrophoresis devices, but hCoFGE is much easier to perform. For data
      analysis, commercial software capable of warping can be adapted.

PMID- 29019126
TI  - DIGE-Based Phosphoproteomic Analysis.
AB  - Here, we describe the detailed step-by-step protocol for detection of
      phosphoproteins in two-dimensional difference gel electrophoresis (DIGE) gels. A
      standard DIGE protocol is combined with subsequent post-staining with
      phosphospecific fluorescent dye. The combination of these two methods complements
      DIGE-based proteome profiling by fluorescence detection of phosphoproteins in the
      same gel providing additional possibility for sensitive and accurate
      quantification of the differentially regulated phosphoproteins in biological
      samples.

PMID- 29019127
TI  - DIGE Saturation Labeling for Scarce Amounts of Protein from Formalin-Fixed
      Paraffin-Embedded (FFPE) Tissue.
AB  - In this chapter, we describe the utility of difference gel electrophoresis (DIGE)
      as a proteomics platform for the global detection of expressed proteins in
      formalin-fixed paraffin-embedded (FFPE) tissues and its use for biomarker
      discovery/identification of proteins that may contribute to cancer development
      and progression. Formalin fixation and paraffin embedding of tissue is the
      standard processing methodology practiced in pathology laboratories worldwide,
      resulting in a highly stable form of tissue that is easily stored due to its
      inherent stability at room temperature. Consequently, FFPE tissues represent an
      attractive reservoir of clinical material for conducting retrospective protein
      biomarker analysis. A limitation for proteomics research in this type of clinical
      sample is the amount of viable protein that can be obtained from fixed tissues.
      Tissue biopsies are precious samples that can generally be acquired in very small
      amounts due to the invasive nature of the sample collection, mainly during
      surgery or biopsy. Subsequently, the amount of extracted protein can be, in many
      cases, very limited. The saturation DIGE technology has emerged as a useful
      method for protein analysis where only scarce amounts of protein are available.
      This approach can be adapted successfully to label low-level protein isolated
      from FFPE tissue.

PMID- 29019128
TI  - Comparative 3-Sample DIGE Analysis of Skeletal Muscles.
AB  - The skeletal muscle proteome consists of a large number of diverse protein
      species with a broad and dynamic concentration range. Since mature skeletal
      muscles are characterized by a specific combination of contractile cells with
      differing physiological and biochemical properties, it is essential to determine
      specific differences in the protein composition of fast, slow, and hybrid fibers.
      Fluorescence two-dimensional gel electrophoresis (DIGE) is a powerful comparative
      tool to analyze fiber type-specific differences between fast and slow muscles. In
      this chapter, the application of the DIGE method for the comparative analysis of
      different subtypes of skeletal muscles is outlined in detail. A standardized
      proteomic workflow is described, involving sample preparation, protein
      extraction, differential fluorescence labeling using a 3-dye system, first
      dimension isoelectric focusing, second-dimension slab gel electrophoresis, DIGE
      image analysis, protein digestion, and mass spectrometry.

PMID- 29019129
TI  - DIGE Analysis of ProteoMinerTM Fractionated Serum/Plasma Samples.
AB  - The discovery of clinically relevant biomarkers using gel-based proteomics has
      proven extremely challenging, principally because of the large dynamic range of
      protein abundances in biofluids such as blood and the fact that only a small
      number of proteins constitute the vast majority of total blood protein mass.
      Various separation, depletion, enrichment, and quantitative developments coupled
      with improvements in gel-based protein quantification technologies, specifically
      difference gel electrophoresis (DIGE), have contributed to significant
      improvements in the detection and identification of lower abundance proteins. One
      of these enrichment technologies, Proteominer, will be the focus of this chapter.
      The Proteominer technology a utilizes hexapeptide bead library with huge
      diversity to bind and enrich low-abundance proteins but at the same time
      suppressing the concentration of high-abundance proteins in subsequent analysis.

PMID- 29019130
TI  - DIGE Analysis of Human Tissues.
AB  - Two-dimensional difference gel electrophoresis (2-D DIGE) is an advanced and
      elegant gel electrophoretic analytical tool for comparative protein assessment.
      It is based on two-dimensional gel electrophoresis (2-DE) separation of
      fluorescently labeled protein extracts. The tagging procedures are designed to
      not interfere with the chemical properties of proteins with respect to their pI
      and electrophoretic mobility, once a proper labeling protocol is followed. The
      two-dye or three-dye systems can be adopted and their choice depends on specific
      applications. Furthermore, the use of an internal pooled standard makes 2-D DIGE
      a highly accurate quantitative method enabling multiple protein samples to be
      separated on the same two-dimensional gel. The image matching and cross-gel
      statistical analysis generates robust quantitative results making data validation
      by independent technologies successful.

PMID- 29019131
TI  - DIGE Analysis of Animal Tissues.
AB  - Two-dimensional difference gel electrophoresis (2D-DIGE) is an acrylamide gel
      electrophoresis-based technique for protein separation and quantification in
      complex mixtures. The technique addresses some of the drawbacks of conventional
      2D polyacrylamide gel electrophoresis (2D-PAGE), offering improved sensitivity,
      more limited experimental variation and accurate within-gel matching. DIGE is
      based on direct labeling of proteins with isobaric fluorescent dyes (known as
      CyDyes: Cy2, Cy3, and Cy5) prior to isoelectric focusing (IEF). Here, up to two
      samples and a reference pool (internal standard) can be mixed and loaded onto IEF
      for first dimension prior to SDS-PAGE separation in the second dimension. After
      the electrophoretic run, the gel is imaged at the specific excitation wavelength
      for each dye, in sequence, and gel scans are recorded separately. For each
      individual protein spot, intensities recorded at the different wavelengths are
      integrated and the ratio between volumes normalized to that of the internal
      standard. This provides an immediate appreciation of protein amount variations
      under the different conditions tested. In addition, proteins of interest can
      still be excised and identified with conventional mass spectrometry techniques
      and further analyzed by other biochemical methods. In this chapter, we describe
      the application of this methodology to separation and quantitation of proteins
      mixtures from porcine muscle exudate, collected following centrifugation of
      muscle specimens (centrifugal drip) for the characterization of quality
      parameters of importance in the meat industry.

PMID- 29019132
TI  - Rapid 2D DIGE Proteomic Analysis of Mouse Liver.
AB  - Several years have passed since LC-MS(/MS) became the mainstream for proteomic
      analysis; however, conventional 2D DIGE (two-dimensional difference gel
      electrophoresis) continues to be an important technology that enables rapid and
      direct visualization of hundreds to thousands of proteins and their quantitative
      analyses. We can get global proteomic views using 2D DIGE within 3 days, and then
      identify proteins with differential expression levels using MALDI-TOF/MS and
      MASCOT search engine within a week. Here, we describe our routine 2D DIGE
      proteomic analysis of the liver isolated from mice in pathological conditions.

PMID- 29019133
TI  - Proteomic Analysis of Lung Tissue by DIGE.
AB  - Lungs perform an essential physiological function, mediated by a complex series
      of events that involve the coordination of multiple cell types to support not
      only gaseous exchange, but homeostasis and protection from infection. Guinea pigs
      are an important animal disease model for a number of infectious and
      noninfectious pulmonary conditions and the availability of a complete genome
      facilitates comprehensive analysis of tissues using the tools of proteomics.
      Here, we describe the application of 2-D Difference Gel Electrophoresis (DIGE) to
      compare, quantify, and identify differential protein expression of proteins in
      lung tissue from guinea pigs with leptospiral pulmonary hemorrhage syndrome
      (LPHS) compared to noninfected controls. 2-D DIGE is a powerful technique that
      provides novel insights into the dynamics of the complex lung proteome during
      health and disease.

PMID- 29019134
TI  - Comparative Testis Tissue Proteomics Using 2-Dye Versus 3-Dye DIGE Analysis.
AB  - Comparative tissue proteomics aims to analyze alterations of the proteome in
      response to a stimulus. Two-dimensional difference gel electrophoresis (2D-DIGE)
      is a modified and advanced form of 2D gel electrophoresis. DIGE is a powerful
      biochemical method that compares two or three protein samples on the same
      analytical gel, and can be used to establish differentially expressed protein
      levels between healthy normal and diseased pathological tissue sample groups.
      Minimal DIGE labeling can be used via a 2-dye system with Cy3 and Cy5 or a 3-dye
      system with Cy2, Cy3, and Cy5 to fluorescently label samples with CyDye flours
      pre-electrophoresis. DIGE circumvents gel-to-gel variability by multiplexing
      samples to a single gel and through the use of a pooled internal standard for
      normalization. This form of quantitative high-resolution proteomics facilitates
      the comparative analysis and evaluation of tissue protein compositions. Comparing
      tissue groups under different conditions is crucially important for advancing the
      biomedical field by characterization of cellular processes, understanding
      pathophysiological development and tissue biomarker discovery. This chapter
      discusses 2D-DIGE as a comparative tissue proteomic technique and describes in
      detail the experimental steps required for comparative proteomic analysis
      employing both options of 2-dye and 3-dye DIGE minimal labeling.

PMID- 29019135
TI  - DIGE Analysis of Fish Tissues.
AB  - Two-dimensional difference gel electrophoresis (2D-DIGE) appears to be especially
      useful in quantitative approaches, allowing the co-separation of proteins of
      control samples from proteins of treatment/disease samples on the same gel,
      eliminating gel-to-gel variability. The principle of 2D-DIGE is to label proteins
      prior to isoelectric focusing and use three spectrally resolvable fluorescent
      dyes, allowing the independent labeling of control and experimental samples. This
      procedure makes it possible to reduce the number of gels in an experiment,
      allowing the accurate and reproducible quantification of multiple samples. 2D
      DIGE has been found to be an excellent methodical tool in several areas of fish
      research, including environmental pollution and toxicology, the mechanisms of
      development and disorders, reproduction, nutrition, evolution, and ecology.

PMID- 29019136
TI  - Protein Digestion for DIGE Analysis.
AB  - In-gel digestion of protein spots derived from two-dimensional gels and their
      subsequent identification by mass spectrometry is involved in a multitude of mass
      spectrometry-driven proteomic experiments, including fluorescence difference gel
      electrophoresis (DIGE). This type of proteomic methodology has been involved in
      the establishment of comparative proteome maps and in the identification of
      differentially expressed proteins and protein isoforms in health and disease.
      Most in-gel digestion protocols follow a number of common steps including
      excision of the protein spots of interest, de-staining, reduction and alkylation
      (for silver-stained gels), dehydration and overnight digestion with the
      proteolytic enzyme of choice. While trypsin has been a mainstay of peptide
      digestion for many years, it does have its shortcomings, particularly related to
      incomplete peptide digestion, and this has led to a rise in popularity for other
      proteolytic enzymes either used alone or in combination. This chapter discusses
      the alternative enzymes available and describes the process of in-gel digestion
      using the enzyme trypsin.

PMID- 29019137
TI  - Subcellular Fractionation for DIGE-Based Proteomics.
AB  - Mass spectrometry-based protein methodologies have revolutionized the field of
      analytical biochemistry and enable the identification of hundreds to thousands of
      proteins in biological fluids, cell lines, and tissue. This methodology requires
      the initial separation of a protein constellation and this has been successfully
      achieved using gel-based techniques, particularly that of two-dimensional
      difference gel electrophoresis (2D-DIGE). However, given the complexity of the
      proteome, fractionation techniques may be required to optimize the detection of
      low-abundance proteins, which are often under-represented, but which may
      represent important players in health and disease. Such subcellular fractionation
      protocols typically utilize density-gradient centrifugation and have enabled the
      enrichment of crude microsomes, the cytosol, the plasmalemma, the nuclei, and the
      mitochondria. In this chapter, we describe the experimental steps involved in the
      enrichment of crude microsomes from skeletal muscle using differential
      centrifugation and subsequent verification of enrichment by gel electrophoresis
      and immunoblotting, prior to comparative DIGE analysis.

PMID- 29019138
TI  - DIGE Analysis of Immunodepleted Plasma.
AB  - This chapter will focus on upstream immunodepletion of high abundant proteins
      from plasma samples and subsequent analysis by difference gel electrophoresis
      (DIGE). The abundances of proteins in biofluid proteomes, such as serum, plasma,
      saliva, and bronchoalveolar lavage fluid (BALF), can exceed 10 orders of
      magnitude. This substantial dynamic range is problematic for the detection of
      medium and low abundance proteins by DIGE analysis. To increase the detection,
      quantification, and identification of medium-low abundant proteins, the targeted
      depletion of known abundant proteins with antibody columns has been successfully
      employed. From the literature, it is clear that the performance of abundant
      protein depletion with immunodepletion columns has been successful in broadening
      the coverage of the biofluid proteome and facilitating the identification of
      disease-specific biomarkers. The task for a successful biomarker strategy
      involves the combination of a reproducible and robust fractionation method,
      coupled with a highly accurate quantitative method, a task that is exemplified by
      combining both immunodepletion and DIGE together to discover significant proteins
      associated with the disease phenotype.

PMID- 29019139
TI  - Elucidating Cellular Metabolism and Protein Difference Data from DIGE Proteomics
      Experiments Using Enzyme Assays.
AB  - Assays for measuring enzyme activity can be useful tools for proteomics
      applications. Enzyme testing can be performed to validate an experimental system
      prior to a Difference Gel Electrophoresis (DIGE) proteomic experiment and can
      also be utilized as an integral part of multifaceted experiment in conjunction
      with DIGE. Data from enzyme tests can be used to corroborate results of DIGE
      proteomic experiments where an enzyme or enzymes are demonstrated by DIGE to be
      differentially expressed. Enzyme testing can also be utilized to support data
      from DIGE experiments that demonstrate metabolic changes in a biological system.
      The different types of enzyme assays that can be performed in conjunction with
      DIGE experiments are reviewed alongside a discussion of experimental approaches
      for designing enzyme assays.

PMID- 29019140
TI  - Enzyme Assay Methods to Validate DIGE Proteomics Data.
AB  - Enzyme activity assay methods can be used to corroborate the results generated by
      Difference Gel Electrophoresis (DIGE) proteomic experiments. Two assay methods
      were chosen to demonstrate how this can be achieved. Assays for determining the
      activity of superoxide dismutase and NADH dehydrogenase are outlined in detail in
      this paper. These methods were chosen as examples because they are frequently
      used in conjunction with DIGE proteomics.

PMID- 29019141
TI  - Immunoblot Analysis of DIGE-Based Proteomics.
AB  - Proteins can be separated according to their size by gel electrophoresis and
      further analyzed by Western blotting. The proteins can be transferred to a
      membrane made of nitrocellulose or polyvinylidene fluoride (PVDF), which results
      in a replica of the proteins' separation patterns. The proteins on the membrane
      can be detected by specific antibodies followed by visualization either on the
      membrane itself, on film or by CCD cameras. Western blotting is a sensitive
      technique to verify data obtained from difference gel electrophoresis (DIGE)
      based proteomics.

PMID- 29019142
TI  - Immunofluorescence Microscopy for DIGE-Based Proteomics.
AB  - Alterations in the proteome of a tissue in different settings, as assessed by
      difference gel electrophoresis, can be verified for single proteins using
      immunohistochemistry. In fluorescence immunohistochemistry, an antibody to a
      particular antigen is applied to tissue sections, and fluorophores conjugated to
      a secondary antibody allow for the detection of target antigen with fluorescent
      microscopy. Visual comparison is sufficient for the detection of significant
      alterations in the abundance of a certain protein in different settings.
      Additionally, unlike large-scale proteome analyses and Western blot methods,
      expression of target protein can be analyzed at the cellular level by
      immunohistochemistry. In this chapter, a protocol for the application of
      fluorescence immunohistochemistry for the detection of dystrophin in skeletal
      muscle sections is outlined, including sample preparation, tissue sectioning, and
      immunostaining.

PMID- 29019143
TI  - Structure and mechanism of plant histone mark readers.
AB  - In eukaryotes, epigenetic-based mechanisms are involved in almost all the
      important biological processes. Amongst different epigenetic regulation pathways,
      the dynamic covalent modifications on histones are the most extensively
      investigated and characterized types. The covalent modifications on histone can
      be "read" by specific protein domains and then subsequently trigger downstream
      signaling events. Plants generally possess epigenetic regulation systems similar
      to animals and fungi, but also exhibit some plant-specific features. Similar to
      animals and fungi, plants require distinct protein domains to specifically "read"
      modified histones in both modification-specific and sequence-specific manners. In
      this review, we will focus on recent progress of the structural studies on the
      recognition of the epigenetic marks on histones by plant reader proteins, and
      further summarize the general and exceptional features of plant histone mark
      readers.

PMID- 29019144
TI  - Role of microbiota on lung homeostasis and diseases.
AB  - The lungs, as a place of gas exchange, are continuously exposed to environmental
      stimuli, such as allergens, microbes, and pollutants. The development of the
      culture-independent technique for microbiological analysis, such as 16S rRNA
      sequencing, has uncovered that the lungs are not sterile and, in fact, colonized
      by diverse communities of microbiota. The function of intestinal microbiota in
      modulating mucosal homeostasis and defense has been widely studied; however, the
      potential function of lung microbiota in regulating immunity and homeostasis has
      just begun. Increasing evidence indicates the relevance of microbiota to lung
      homeostasis and disease. In this review, we describe the distribution and
      composition of microbiota in the respiratory system and discuss the potential
      function of lung microbiota in both health and acute/chronic lung disease. In
      addition, we also discuss the recent understanding of the gut-lung axis, because
      several studies have revealed that the immunological interaction among the gut,
      the lung, and the microbiota was involved in this issue.

PMID- 29019145
TI  - Phylogenetic and genetic characterization of a 2017 clinical isolate of H7N9
      virus in Guangzhou, China during the fifth epidemic wave.
AB  - Pathogenic H7N9 influenza viruses continue to pose a public health concern. The
      H7N9 virus has caused five outbreak waves of human infections in China since
      2013. In the present study, a novel H7N9 strain (A/Guangdong/8H324/2017) was
      isolated from a female patient with severe respiratory illness during the fifth
      wave of the 2017 H7N9 epidemic. Phylogenetic analysis showed that the H7N9
      viruses collected during the fifth wave belong to two different lineages: the
      Pearl River Delta lineage and the Yangtze River Delta lineage. The novel isolate
      is closely related to the Pearl River Delta H7N9 viruses, which were isolated
      from patients in Guangdong Province. The novel H7N9 isolate has an insertion of
      three basic amino acids in the cleavage site of hemagglutinin (HA), which may
      enhance virulence in poultry. The 2017 isolate also possesses an R292K
      substitution in the neuraminidase (NA) protein, which confers oseltamivir
      resistance. This study highlights the pandemic potential of the novel H7N9 virus
      in mammals; thus, future characterization and surveillance is warranted.

PMID- 29019147
TI  - MRI and multiple sclerosis-the evolving role of MRI in the diagnosis and
      management of MS: a clinician's perspective.
AB  - The diagnosis of multiple sclerosis (MS) is based on a history consistent with
      demyelination of the central nervous system and corresponding physical signs on
      examination. However, this diagnosis is supported radiologically using magnetic
      resonance imaging (MRI). At present, MRI serves as the most reliable and widely
      available biomarker for the practising clinician to measure disease activity and
      treatment response in MS. As MRI remains central to both the diagnosis and
      management of MS, this paper provides proposed guidelines for its use in routine
      clinical practice.

PMID- 29019146
TI  - Spinal cord injury after thoracic endovascular aortic aneurysm repair.
AB  - PURPOSE: Thoracic endovascular aortic aneurysm repair (TEVAR) has become a
      mainstay of therapy for aneurysms and other disorders of the thoracic aorta. The
      purpose of this narrative review article is to summarize the current literature
      on the risk factors for and pathophysiology of spinal cord injury (SCI) following
      TEVAR, and to discuss various intraoperative monitoring and treatment strategies.
      SOURCE: The articles considered in this review were identified through PubMed
      using the following search terms: thoracic aortic aneurysm, TEVAR,
      paralysis+TEVAR, risk factors+TEVAR, spinal cord ischemia+TEVAR,
      neuromonitoring+thoracic aortic aneurysm, spinal drain, cerebrospinal fluid
      drainage, treatment of spinal cord ischemia. PRINCIPAL FINDINGS: Spinal cord
      injury continues to be a challenging complication after TEVAR. Its incidence
      after TEVAR is not significantly reduced when compared with open thoracoabdominal
      aortic aneurysm repair. Nevertheless, compared with open procedures, delayed
      paralysis/paresis is the predominant presentation of SCI after TEVAR. The
      pathophysiology of SCI is complex and not fully understood, though the evolving
      concept of the importance of the spinal cord's collateral blood supply network
      and its imbalance after TEVAR is emerging as a leading factor in the development
      of SCI. Cerebrospinal fluid drainage, optimal blood pressure management, and
      newer surgical techniques are important components of the most up-to-date
      strategies for spinal cord protection. CONCLUSION: Further experimental and
      clinical research is needed to aid in the discovery of novel neuroprotective
      strategies for the protection and treatment of SCI following TEVAR.

PMID- 29019149
TI  - Leukemia Inhibitory Factor Increases Survival of Pluripotent Stem Cell-Derived
      Cardiomyocytes.
AB  - Leukemia inhibitory factor (LIF) is a growth factor with pleiotropic biological
      functions. It has been reported that LIF acts at different stages during mesoderm
      development. Also, it has been shown that LIF has a cytoprotective effect on
      neonatal murine cardiomyocytes (CMs) in culture, but little is known about the
      role of LIF during human cardiogenesis. Thus, we analyzed the effects of LIF on
      human pluripotent stem cells (PSC) undergoing cardiac differentiation. We first
      showed that LIF is expressed in the human heart during early development. We
      found that the addition of LIF within a precise time window during the in vitro
      differentiation process significantly increased CMs viability. This finding was
      associated to a decrease in the expression of pro-apoptotic protein Bax, which
      coincides with a reduction of the apoptotic rate. Therefore, the addition of LIF
      may represent a promising strategy for increasing CMs survival derived from PSCs.

PMID- 29019148
TI  - Modulating what is and what could have been: The effect of transcranial direct
      current stimulation on the evaluation of attained and unattained decision
      outcomes.
AB  - The affective evaluation of decision outcomes, whether attained (e.g.,
      disappointment) or based on the conscious realization that a decision made
      differently would have led to a better or worse outcome (e.g., regret), greatly
      influence future decisions. Prior research has demonstrated a role of the medial
      and orbitofrontal cortex (M/OFC) in decision valuation and the experience of
      regret and relief. Here we examined whether inhibitory transcranial direct
      current stimulation (tDCS) could dampen the experience of decision-induced
      affect, with a focus on regret and relief. Thirty-eight participants completed a
      previously used gambling task and were asked to rate their happiness with
      attained outcomes of a chosen gamble before and after being shown unattained,
      counterfactual outcomes (i.e., what would have happened had they selected the
      other gamble). The difference in happiness rating before and after revealing
      these unattained counterfactual outcomes was taken as a measure of regret
      (negative shift) or relief (positive shift). During this task, 20 participants
      received 2 mA cathodal tDCS over EEG coordinate Fp1 for 20 minutes, and 18
      participants received sham stimulation over the same location. Linear mixed-model
      results showed that, compared to sham, participants who received cathodal tDCS
      reported less intense emotions in response to attained as well as counterfactual
      outcomes. These findings were not due to the groups differing in the gambles they
      selected or attained monetary outcomes, demonstrating that tDCS can modulate
      decision-induced (counterfactual) affect. This may have implications for the
      ability to modulate value-based decision-making using brain stimulation
      techniques more broadly.

PMID- 29019151
TI  - Bariatric Surgery Is Acceptably Safe in Obese Inflammatory Bowel Disease
      Patients: Analysis of the Nationwide Inpatient Sample.
AB  - BACKGROUND: The prevalence of obesity in patients with inflammatory bowel disease
      (IBD) has increased over the past decades. Data to support the safety of
      bariatric surgery (BAR) in IBD remain scarce. Our aim was to evaluate the safety
      and early postoperative complications of BAR in IBD patients. METHODS: We used
      the Nationwide Inpatient Sample (NIS) 2011, 2012, and 2013 to perform a cohort
      study. The study group was all hospitalized patients between ages 18-90 years who
      underwent BAR with a discharge diagnosis of IBD as per the Ninth International
      Classification of Diseases codes (ICD-9). Adults who underwent BAR without ICD-9
      codes of IBD were identified as the comparison group. Complications were compared
      using multivariate logistic regression analysis. RESULTS: We identified 314,864
      adult patients who underwent BAR between 2011 and 2013. Mean age was 45.5 +/-
      0.11 years, and 79% were females. Seven hundred and ninety patients had
      underlying IBD; 459 had Crohn's disease and 331 had ulcerative colitis. The
      remaining patients formed the comparison group. Mean length of hospital stay
      (LOS) was longer in the IBD group by 1 day (p = 0.01). The IBD group had a
      significantly higher risk of perioperative small bowel obstruction (SBO)
      (adjusted odds ratio, 4.0; 95%, CI; 2.2-7.4). Other technical and systemic
      complications were similar between the two groups, with no mortality reported in
      the IBD group. CONCLUSIONS: BAR in IBD patients has an acceptable safety profile,
      with immeditae risk limited to perioperative SBO and an apparently low risk of
      mortality or other major immediate postoperative complications.

PMID- 29019152
TI  - Travel Warning.

PMID- 29019153
TI  - Emperor's New.

PMID- 29019154
TI  - Michael Angel.

PMID- 29019156
TI  - Where Did He Go?

PMID- 29019150
TI  - The Zollinger-Ellison syndrome: is there a role for somatostatin analogues in the
      treatment of the gastrinoma?
AB  - PURPOSE: Analyze the role of somatostatin analogues (SSAs) in the treatment of
      sporadic and MEN1-related gastrinomas, trying to define whether recent trials
      have changed the landscape of gastrinoma therapy. METHODS: We evaluate the
      rationale of SSA use in the treatment of gastrinomas, summarize the current
      literature concerning the effect of SSAs on the control of Zollinger-Ellison
      syndrome (ZES) and gastrinomas tumor progression and discuss their role in the
      most recent guidelines. RESULTS: The medical treatment of gastrinoma and related
      ZES is aimed at controlling acid hypersecretion and tumor progression, in
      inoperable patients. The use of proton pump inhibitors (PPIs) to control the
      syndrome is a cornerstone in the ZES therapy. SSAs are not usually indicated for
      antisecretory purpose, because PPIs are considered the treatment of choice, due
      to their long lasting high efficacy and oral availability. The antiproliferative
      effect of SSAs has been established by two placebo-controlled trials that have
      clearly demonstrated a significant increase in progression free survival in
      patients affected by non-functioning well-differentiated advanced neuroendocrine
      tumors (NETs). The recent ENETS guidelines recommend the use of SSAs in advanced
      well differentiated NETs as antiproliferative agents. CONCLUSIONS: The high sstr
      expression in gastrinomas make them highly responsive to SSAs and support the use
      of such drugs to counteract the tumour growth in patients not amenable to
      surgical cure. Unfortunately, limited data, mainly case reports or small series,
      support the use of SSAs in advanced gastrinomas, therefore, it is difficult to
      quantify their ability to control tumour growth and disease progression.

PMID- 29019157
TI  - Does neighborhood size really cause the word length effect?
AB  - In short-term serial recall, it is well-known that short words are remembered
      better than long words. This word length effect has been the cornerstone of the
      working memory model and a benchmark effect that all models of immediate memory
      should account for. Currently, there is no consensus as to what determines the
      word length effect. Jalbert and colleagues (Jalbert, Neath, Bireta, & Surprenant,
      2011a; Jalbert, Neath, & Surprenant, 2011b) suggested that neighborhood size is
      one causal factor. In six experiments we systematically examined their
      suggestion. In Experiment 1, with an immediate serial recall task, multiple word
      lengths, and a large pool of words controlled for neighborhood size, the typical
      word length effect was present. In Experiments 2 and 3, with an order
      reconstruction task and words with either many or few neighbors, we observed the
      typical word length effect. In Experiment 4 we tested the hypothesis that the
      previous abolition of the word length effect when neighborhood size was
      controlled was due to a confounded factor: frequency of orthographic structure.
      As predicted, we reversed the word length effect when using short words with less
      frequent orthographic structures than the long words, as was done in both of
      Jalbert et al.'s studies. In Experiments 5 and 6, we again observed the typical
      word length effect, even if we controlled for neighborhood size and frequency of
      orthographic structure. Overall, the results were not consistent with the
      predictions of Jalbert et al. and clearly showed a large and reliable word length
      effect after controlling for neighborhood size.

PMID- 29019158
TI  - Cost-effectiveness of nurse-delivered cognitive behavioural therapy (CBT)
      compared to supportive listening (SL) for adjustment to multiple sclerosis.
AB  - BACKGROUND: Cognitive Behavioural Therapy (CBT) reduces distress in multiple
      sclerosis, and helps manage adjustment, but cost-effectiveness evidence is
      lacking. METHODS: An economic evaluation was conducted within a multi-centre
      trial. 94 patients were randomised to either eight sessions of nurse-led CBT or
      supportive listening (SL). Costs were calculated from the health, social and
      indirect care perspectives, and combined with additional quality-adjusted life
      years (QALY) or improvement on the GHQ-12 score, to explore cost-effectiveness at
      12 months. RESULTS: CBT had higher mean health costs (L1610, 95% CI, -L187 to
      3771) and slightly better QALYs (0.0053, 95% CI, -0.059 to 0.103) compared to SL
      but these differences were not statistically significant. This yielded L301,509
      per QALY improvement, indicating that CBT is not cost-effective according to
      established UK NHS thresholds. The extra cost per patient improvement on the GHQ
      12 scale was L821 from the same perspective. Using a L20,000, threshold, CBT in
      this format has a 9% probability of being cost effective. Although subgroup
      analysis of patients with clinical levels of distress at baseline showed an
      improvement in the position of CBT compared to SL, CBT was still not cost
      effective. CONCLUSION: Nurse delivered CBT is more effective in reducing distress
      among MS patients compared to SL, but is highly unlikely to be cost-effective
      using a preference-based measure of health (EQ-5D). Results from a disease
      specific measure (GHQ-12) produced comparatively lower Incremental Cost
      Effectiveness Ratios, but there is currently no acceptable willingness-to-pay
      threshold for this measure to guide decision-making.

PMID- 29019160
TI  - The role of cognitive reserve in cognitive aging: what we can learn from
      Parkinson's disease.
AB  - Parkinson's disease (PD) typically occurs in elderly people and some degree of
      cognitive impairment is usually present. Cognitive reserve (CR) theory was
      proposed to explain the discrepancy between the degree of brain pathologies and
      clinical manifestations. We administered a comprehensive neuropsychological
      battery to 35 non-demented participants affected by PD. All participants
      underwent also the Cognitive Reserve Index questionnaire and the Brief
      Intelligence Test as proxies for CR. Relationships between CR and cognitive
      performance were investigated by linear regression analyses, adjusting for
      significant confounding factors. At linear regression analyses, higher CR scores
      were independently associated with a better performance on Word Fluency (p <=
      0.04) and Digit Span (backward) (p <= 0.02); no associations were observed
      between CR and other cognitive tests. Our data provide empirical support to the
      relation between CR and cognitive impairment in PD. In particular, this study
      suggests that CR may have greater effects on the cognitive areas mostly affected
      in PD as executive functions.

PMID- 29019159
TI  - Alpha Lipoamide Ameliorates Motor Deficits and Mitochondrial Dynamics in the
      Parkinson's Disease Model Induced by 6-Hydroxydopamine.
AB  - The precise mechanisms underlying neuronal injury in Parkinson's disease (PD) are
      not yet fully elucidated; however, evidence from the in vitro and in vivo PD
      models suggest that mitochondrial dysfunction may play a major role in PD
      pathogenesis. Alpha lipoamide, a neutral amide derivative of the lipoic acid, is
      a better cofactor for mitochondrial dehydrogenase with a stronger protective
      effect on mitochondria than lipoic acid. Identification of these protective
      effects of alpha lipoamide on mitochondria, together with the evidence that
      mitochondrial dysfunction plays a critical role in PD, we speculate that alpha
      lipoamide may exert a protective effect in PD by regulating the mitochondrial
      function. The present study investigated the neuroprotective effects of alpha
      lipoamide in an animal model of PD induced by 6-hydroxydopamine (6-OHDA). The
      results demonstrated that alpha lipoamide could significantly antagonize the 6
      OHDA-induced behavioral damages; restore ATP levels in the midbrain; and also
      improve the fragmentation, vacuolization, and morphology of the mitochondria. The
      results of Western blot indicated that alpha lipoamide significantly restored the
      number of dopaminergic neurons in midbrain and substantially recovered the
      balance between mitochondrial fission, fusion, and transport. In conclusion, the
      results demonstrated that alpha lipoamide might exert a significant
      neuroprotective effect in the animal model of PD by regulation of the dynamic
      properties of mitochondria.

PMID- 29019162
TI  - LsrB-based and temperature-dependent identification of bacterial AI-2 receptor.
AB  - The luxS gene is required for autoinducer-2 (AI-2) synthesis in many bacterial
      species. AI-2 is taken up by a specific receptor to regulate multiple bacterial
      activities. However, the lack of methods to identify AI-2 receptors has impeded
      investigations into the roles of AI-2. Here, a luxS mutant of Escherichia coli
      strain BL21 (DE3) was constructed (named BL21?luxS), and the recombinant LsrB
      protein of Salmonella enterica was expressed in BL21?luxS and BL21 cells, which
      were named LsrB (BL21?luxS) and LsrB (BL21), respectively. The results of the
      activity of recombinant LsrB binding showed that LsrB (BL21) bound to endogenous
      AI-2 (produced from BL21 strain), while LsrB (BL21?luxS) did not (as BL21?luxS
      cannot produce AI-2). However, the results of recombinant LsrB binding showed
      that LsrB (BL21?luxS) can bind exogenous AI-2, which was released from LsrB
      (BL21?luxS) at 55  degrees C for 10 min, while LsrB (BL21) could not bind
      exogenous AI-2 (due to binding of endogenous AI-2 before). Furthermore, analysis
      of the thermal stability of AI-2 showed that that AI-2 activity was relatively
      high at incubation temperatures below 65  degrees C. These findings will be
      beneficial for screening of new AI-2 receptors in different bacterial species.

PMID- 29019161
TI  - Assessing the Use of a Feedback Module to Model EQ-5D-5L Health States Values in
      Hong Kong.
AB  - BACKGROUND: An international valuation protocol exists for obtaining societal
      values for each of the 3125 health states of the five-level EuroQol-five
      dimensions (EQ-5D-5L) questionnaire. A feedback module (FM) that can be related
      to theoretical models used in behavioral economics was recently included in this
      protocol. OBJECTIVES: Our objective was to assess the impact of using an FM to
      estimate an EQ-5D-5L value set in Hong Kong. METHODS: EQ-5D-5L health states were
      elicited using a composite time trade-off (C-TTO) and a discrete-choice (DC)
      experiment. Use of the FM according to participant characteristics and the impact
      of the FM on the number of inconsistent C-TTO responses were assessed. We
      employed a main-effects hybrid model that combined data from both elicitation
      techniques. RESULTS: In total, 1014 individuals completed the survey. The sample
      was representative of the general Chinese Hong Kong population in terms of sex,
      educational attainment, marital status, and most age groups but not for
      employment status. The use of the FM reduced the number of C-TTO inconsistencies.
      Participant characteristics differed significantly between those who used and did
      not use the FM. The model without a constant resulted in logical consistent
      coefficients and was therefore selected as the model to produce the value set.
      The predicted EQ-5D-5L values ranged from -0.864 to 1. CONCLUSIONS: The use of an
      FM to allow participants to exclude C-TTO responses reduced the number of
      inconsistent responses and improved the quality of the data when estimating an EQ
      5D-5L value set in Hong Kong.

PMID- 29019163
TI  - Enzyme replacement therapy in a patient of heterozygous Fabry disease: clinical
      and pathological evaluations by repeat kidney biopsy and a successful pregnancy.
AB  - Fabry disease is a rare X-linked lysosomal storage disorder of glycosphingolipid
      catabolism caused by deficient activity of the lysosomal hydrolase alpha
      galactosidase A (alpha-Gal A). A 20-year-old woman was referred to our hospital
      because of proteinuria and persistent macroscopic hematuria. Based on the typical
      renal pathological findings, deficient activity of the alpha-Gal A, and
      heterozygous mutation in the alpha-Gal A gene, she was diagnosed with Fabry
      disease. After 1 year of enzyme replacement therapy with agalsidase alfa at 0.2
      mg/kg every other week, the patient's proteinuria and hematuria were disappeared.
      In our patient, enzyme replacement therapy with agalsidase alfa was observed to
      be safe and well-tolerated during her pregnancy, with no significant negative
      effects on her or her child. Here, we report clinical and pathological
      evaluations of a patient through repeat kidney biopsy after 6 years of enzyme
      replacement therapy. Furthermore, we discussed the appropriate enzyme replacement
      therapy and its safety in pregnant women with Fabry disease.

PMID- 29019165
TI  - Correction to: Variations of characteristic time scales in rotating stratified
      turbulence using a large parametric numerical study.
AB  - After publication of the paper, an error in computing the ratio gamma of kinetic
      to potential energy transfer times has been detected, which has led the authors
      to amend two figures, as explained in the main text.

PMID- 29019164
TI  - Tuberculosis of the Breast in Togo: A Series of 28 Presumed Cases.
AB  - Our study aimed to describe the epidemiological, clinical and histological
      aspects of mammary tuberculosis in Togo. This is a descriptive cross-sectional
      study of breast tuberculosis for which the diagnosis was presumed on histological
      grounds in the pathology department (LAP) of the Lome Tokoin university hospital
      from January 1995 to December 2016 (20 years). A total of 28 presumed cases of
      mammary tuberculosis were identified. There were 26 women and 2 men, with an
      average age of 34.2 +/- 0.3 years. The clinical signs were nodule (84.1%),
      tumefaction (75%), abscess (63.6%) and tumefaction with cutaneous fistulization
      (59.1%). Breast involvement was isolated in 31.8% of cases and associated with
      pleuropulmonary tuberculosis in 54.5% of cases. Co-infection with HIV was found
      in 63.9 % of cases. Histology showed inflammatory granulomas made of Langhans
      giant cells, epithelioid cells and lymphocytes around the foci of caseous
      necrosis. Thoracic radiography was abnormal in 16 patients (57.1%).Mammary
      tuberculosis is not rare in our country. Clinical presentation is often
      misleading and is a diagnostic challenge, more particularly with breast abscess
      or cancer.

PMID- 29019167
TI  - Hybrid Simulation in Teaching Clinical Breast Examination to Medical Students.
AB  - Clinical breast examination (CBE) is traditionally taught to third-year medical
      students using a lecture and a tabletop breast model. The opportunity to
      clinically practice CBE depends on patient availability and willingness to be
      examined by students, especially in culturally sensitive environments. We propose
      the use of a hybrid simulation model consisting of a standardized patient (SP)
      wearing a silicone breast simulator jacket and hypothesize that this, compared to
      traditional teaching methods, would result in improved learning. Consenting third
      year medical students (N = 82) at a university-affiliated tertiary care center
      were cluster-randomized into two groups: hybrid simulation (breast jacket + SP)
      and control (tabletop breast model). Students received the standard lecture by
      instructors blinded to the randomization, followed by randomization group-based
      learning and practice sessions. Two weeks later, participants were assessed in an
      Objective Structured Clinical Examination (OSCE), which included three stations
      with SPs blinded to the intervention. The SPs graded the students on CBE
      completeness, and students completed a self-assessment of their performance and
      confidence during the examination. CBE completeness scores did not differ between
      the two groups (p = 0.889). Hybrid simulation improved lesion identification
      grades (p < 0.001) without increasing false positives. Hybrid simulation relieved
      the fear of missing a lesion on CBE (p = 0.043) and increased satisfaction with
      the teaching method among students (p = 0.002). As a novel educational tool,
      hybrid simulation improves the sensitivity of CBE performed by medical students
      without affecting its specificity. Hybrid simulation may play a role in
      increasing the confidence of medical students during CBE.

PMID- 29019166
TI  - Buckling of elastic filaments by discrete magnetic moments.
AB  - We study the buckling of an idealized, semiflexible filament along whose contour
      magnetic moments are placed. We give analytic expressions for the critical
      stiffness of the filament below which it buckles due to the magnetic compression.
      For this, we consider various scenarios of the attachment of the magnetic
      particles to the filament. One possible application for this model are the
      magnetosome chains of magnetotactic bacteria. An estimate of the critical bending
      stiffness indicates that buckling may occur within the range of biologically
      relevant parameters and suggests a role for the bending stiffness of the filament
      to stabilize the filament against buckling, which would compromise the functional
      relevance of the bending stiffness of the used filament.

PMID- 29019168
TI  - Lipids, lipid metabolism and Kaposi's sarcoma-associated herpesvirus
      pathogenesis.
AB  - Lipids are essential for mammalian cells to maintain many physiological
      functions. Emerging evidence has shown that cancer cells can develop specific
      alterations in lipid biosynthesis and metabolism to facilitate their survival and
      various malignant behaviors. To date, the precise role of cellular lipids and
      lipid metabolism in viral oncogenesis is still largely unclear with only a
      handful of literature covering this topic to implicate lipid metabolism in
      oncogenic virus associated pathogenesis. In this review, we focus on the role of
      lipid biosynthesis and metabolism in the pathogenesis of the Kaposi's sarcoma
      associated herpesvirus, a common causative factor for cancers arising in the
      immunocompromised settings.

PMID- 29019169
TI  - One-back reinforcement dissociates implicit-procedural and explicit-declarative
      category learning.
AB  - The debate over unitary/multiple category-learning utilities is reminiscent of
      debates about multiple memory systems and unitary/dual codes in knowledge
      representation. In categorization, researchers continue to seek paradigms to
      dissociate explicit learning processes (yielding verbalizable rules) from
      implicit learning processes (yielding stimulus-response associations that remain
      outside awareness). We introduce a new dissociation here. Participants learned
      matched category tasks with a multidimensional, information-integration solution
      or a one-dimensional, rule-based solution. They received reinforcement
      immediately (0-Back reinforcement) or after one intervening trial (1-Back
      reinforcement). Lagged reinforcement eliminated implicit, information-integration
      category learning but preserved explicit, rule-based learning. Moreover,
      information-integration learners facing lagged reinforcement spontaneously
      adopted explicit rule strategies that poorly suited their task. The results
      represent a strong process dissociation in categorization, broadening the range
      of empirical techniques for testing the multiple-process theoretical perspective.
      This and related methods that disable associative learning-fostering a transition
      to explicit-declarative cognition-could have broad utility in comparative,
      cognitive, and developmental science.

PMID- 29019170
TI  - Drug Delivery from an Innovative LAMA/LABA Co-suspension Delivery Technology
      Fixed-Dose Combination MDI: Evidence of Consistency, Robustness, and Reliability.
AB  - To ensure consistency of clinical outcomes, orally inhaled therapies must exhibit
      consistent delivered dose and aerosol properties at the time of manufacturing,
      throughout storage, and during various patient-use conditions. Achieving
      consistency across these scenarios has presented a significant challenge,
      especially for combination products that contain more than one drug. This study
      characterized the delivered dose and aerosol properties of
      glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI; Bevespi
      AerosphereTM). GFF MDI, a fixed-dose combination (FDC) of a long-acting
      muscarinic antagonist, glycopyrrolate (18 MUg, equivalent to glycopyrronium 14.4
      MUg), and a long-acting beta2-agonist, formoterol fumarate (9.6 MUg; equivalent
      to formoterol fumarate dihydrate 10 MUg), is formulated using innovative co
      suspension delivery technology, which suspends micronized drug crystals with
      spray-dried phospholipid porous particles in hydrofluoroalkane propellant. In
      this study, delivered dose uniformity was assessed through the labeled number of
      doses, and aerosol properties, such as percent fine particle fraction (FPF) and
      mass median aerodynamic diameter, were determined by cascade impaction. GFF MDI
      achieved reproducible dose delivery and an FPF greater than 55%, whether
      formulated and delivered as a monocomponent or dual FDC. The performance of GFF
      MDI was maintained across various manufacturing batches, under extended storage,
      and with variations in flow rate. Furthermore, unlike a GFF drug crystal-only
      suspension, drug delivery remained consistent for GFF MDI when simulated patient
      handling errors were applied, such as reduced shake energy and delays between
      shaking and actuation. These results demonstrate that co-suspension delivery
      technology overcomes well-known sources of variability in MDI drug delivery.

PMID- 29019174
TI  - Awake GlideScope(r)-assisted foreign body retrieval.

PMID- 29019171
TI  - Optimization of culture conditions for rapid clinical-scale expansion of human
      umbilical cord blood-derived mesenchymal stem cells.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) have broad-spectrum therapeutic effects
      in various diseases, and thus have many clinical applications. However, it is
      difficult to produce sufficient numbers of MSCs for clinical use, and improved
      culture systems are required. Here, we report the effects of calcium (Ca2+) and
      hypoxia on the proliferation of human umbilical cord blood-derived MSCs (hUCB
      MSCs). In addition, we determined the optimal conditions of these two factors for
      the large-scale culture of hUCB-MSCs. METHODS: hUCB-MSCs were maintained under
      hypoxic conditions (3% O2) with 1.8 mM Ca2+ during long-term culture, and their
      proliferation was evaluated. To characterize the underlying mechanisms, the
      effects on hypoxia-inducible factor (HIF)-1alpha and the extracellular signal
      regulated kinase (ERK) signaling pathways were investigated. The therapeutic
      effects in a mouse emphysema model were analyzed and compared with those of naive
      MSCs. RESULTS: The proliferation of Ca2+/hypoxia-treated hUCB-MSCs was increased
      compared with that observed using either calcium or hypoxia culture alone,
      without loss of stem cell marker expression or differentiation ability. The
      enhancement of the proliferation capacity of hUCB-MSCs by the synergistic effects
      of Ca2+ and hypoxia was dependent on the expression of HIF-1alpha and the ERK
      signaling pathway. The proliferation of Ca2+/hypoxia-treated hUCB-MSCs resulted
      in a delayed senescence phenotype and increased the expression levels of stemness
      genes such as Oct4 and Nanog compared to those observed in conventional culture
      conditions. In addition, Ca2+/hypoxia-treated MSCs transplantation in the mouse
      emphysema model showed the same therapeutic effects as observed with naive MSCs.
      CONCLUSIONS: These findings suggest that a Ca2+/hypoxia-based expansion system
      has applications for the large-scale production of MSCs for therapeutic purposes.

PMID- 29019176
TI  - Letter From the Editor-in-Chief: Journal Transition in the Digital Age.

PMID- 29019175
TI  - Isolated Limb Infusion: A Single-Center Experience with Over 200 Infusions.
AB  - BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive technique for
      delivering regional chemotherapy to an extremity for patients with locally
      advanced cutaneous malignancies and sarcoma. METHODS: A single-institution,
      prospectively collected database was analyzed for intention-to-treat with ILI.
      RESULTS: From 2007 to 2016, 163 patients underwent 205 procedures (201 were
      successfully completed), and four malignancies were treated: melanoma (72.1% of
      all ILIs), sarcoma (23.4%), squamous cell carcinoma (SCC; 2.0%) and Merkel cell
      carcinoma (MCC; 2.5%). A median grade II regional Wieberdink toxicity score was
      observed, with 88.1% of patients experiencing grade II or less. Median follow-up
      was 21.8 months, and overall response rate (ORR) was 59.0% for melanoma, 48.9%
      for sarcoma, 50.0% for SCC, and 60.0% for MCC. A significant difference (p =
      0.04) between upper (76.9%) and lower extremity (55.1%) ORR was observed in
      patients with melanoma. When comparing responders with nonresponders, patients
      with melanoma had significantly longer in-field progression-free survival (IPFS;
      14.1 vs. 3.2 months, p < 0.001), distant metastatic-free survival (DMFS; not
      reached vs. 25.8 months, p = 0.006), and overall survival (OS; 56.0 vs. 26.7
      months, p = 0.0004). Sarcoma responders had a significantly longer IPFS (13.0 vs.
      2.7 months, p < 0.0001), but no significant distant metastatic or OS advantage.
      Over a median follow-up of 19.3 months, sarcoma patients had an overall limb
      salvage rate of 68.4%. CONCLUSION: ILI is a well-tolerated procedure for patients
      with locally advanced melanoma, sarcoma, and other cutaneous malignancies. ILI
      responders had a significantly longer time to IPFS, while melanoma responders
      also had a DMFS and OS advantage.

PMID- 29019178
TI  - Second harmonic generation for collagen I characterization in rectal cancer
      patients with and without preoperative radiotherapy.
AB  - Rectal cancer is treated with preoperative radiotherapy (RT) to downstage the
      tumor, reduce local recurrence, and improve patient survival. Still, the
      treatment outcome varies significantly and new biomarkers are desired. Collagen I
      (Col-I) is a potential biomarker, which can be visualized label-free by second
      harmonic generation (SHG). Here, we used SHG to identify Col-I changes induced by
      RT in surgical tissue, with the aim to evaluate the clinical significance of RT
      induced Col-I changes. First, we established a procedure for quantitative
      evaluation of Col-I by SHG in CDX2-stained tissue sections. Next, we evaluated
      Col-I properties in material from 31 non-RT and 29 RT rectal cancer patients. We
      discovered that the Col-I intensity and anisotropy were higher in the tumor
      invasive margin than in the inner tumor and normal mucosa, and RT increased and
      decreased the intensity in inner tumor and normal mucosa, respectively.
      Furthermore, higher Col-I intensity in the inner tumor was related to increased
      distant recurrence in the non-RT group but to longer survival in the RT group. In
      conclusion, we present a new application of SHG for quantitative analysis of Col
      I in surgical material, and the first data suggest Col-I intensity as a putative
      prognostic biomarker in rectal cancer.

PMID- 29019179
TI  - Vessel packaging effect in laser speckle contrast imaging and laser Doppler
      imaging.
AB  - Laser speckle-based techniques are frequently used to assess microcirculatory
      blood flow. Perfusion estimates are calculated either by analyzing the speckle
      fluctuations over time as in laser Doppler flowmetry (LDF), or by analyzing the
      speckle contrast as in laser speckle contrast imaging (LSCI). The perfusion
      estimates depend on the amount of blood and its speed distribution. However, the
      perfusion estimates are commonly given in arbitrary units as they are nonlinear
      and depend on the magnitude and the spatial distribution of the optical
      properties in the tissue under investigation. We describe how the spatial
      confinement of blood to vessels, called the vessel packaging effect, can be
      modeled in LDF and LSCI, which affect the Doppler power spectra and speckle
      contrast, and the underlying bio-optical mechanisms for these effects. As an
      example, the perfusion estimate is reduced by 25% for LDF and often more than 50%
      for LSCI when blood is located in vessels with an average diameter of 40  MUm,
      instead of being homogeneously distributed within the tissue. This significant
      effect can be compensated for only with knowledge of the average diameter of the
      vessels in the tissue.

PMID- 29019180
TI  - [Preface for special issue on bio-based materials (2016)].
AB  - Bio-based materials are new materials or chemicals with renewable biomass as raw
      materials such as grain, legume, straw, bamboo and wood powder. This class of
      materials includes bio-based polymer, biobased fiber, glycotechnology products,
      biobased rubber and plastics produced by biomass thermoplastic processing and
      basic biobased chemicals, for instance, bio-alcohols, organic acids, alkanes, and
      alkenes, obtained by bio-synthesis, bio-processing and bio-refinery. Owing to its
      environmental friendly and resource conservation, bio-based materials are
      becoming a new dominant industry taking the lead in the world scientific and
      technological innovation and economic development. An overview of bio-based
      materials development is reported in this special issue, and the industrial
      status and research progress of the following aspects, including biobased fiber,
      polyhydroxyalkanoates, biodegradable mulching film, bio-based polyamide, protein
      based biomedical materials, bio-based polyurethane, and modification and
      processing of poly(lactic acid), are introduced.

PMID- 29019177
TI  - Long-Term Survival after Complete Surgical Resection and Adjuvant Immunotherapy
      for Distant Melanoma Metastases.
AB  - BACKGROUND: This phase III study was undertaken to evaluate the efficacy of an
      allogeneic whole-cell vaccine (CanvaxinTM) plus bacillus Calmette-Guerin (BCG)
      after complete resection of stage IV melanoma. METHODS: After complete resection
      of <=5 distant metastases, patients were randomly assigned to BCG+Canvaxin
      (BCG/Cv) or BCG+placebo (BCG/Pl). The primary endpoint was overall survival (OS);
      secondary endpoints were disease-free survival (DFS), and immune response
      measured by skin test (ClinicalTrials.gov identifier: NCT00052156). RESULTS:
      Beginning in May 1998, 496 patients were randomized. In April 2005, the Data
      Safety Monitoring Board recommended stopping enrollment due to a low probability
      of efficacy. At that time, median OS and 5-year OS rate were 38.6 months and
      44.9%, respectively, for BCG/Pl versus 31.4 months and 39.6% in the BCG/Cv group
      (hazard ratio (HR), 1.18; p = 0.250). Follow-up was extended at several trial
      sites through March 2010. Median OS and 5-year and 10-year survival was 39.1
      months, 43.3 and 33.3%, respectively, for BCG/Pl versus 34.9 months, 42.5 and
      36.4%, in the BCG/Cv group (HR 1.053; p = 0.696). Median DFS, 5- and 10-year DFS
      were 7.6 months, 23.8 and 21.7%, respectively, for BCG/Pl versus 8.5 months,
      30.0%, and 30.0%, respectively, for the BCG/Cv group (HR 0.882; p = 0.260).
      Positive DTH skin testing correlated with increased survival. DISCUSSION: In
      this, the largest study of postsurgical adjuvant therapy for stage IV melanoma
      reported to date, BCG/Cv did not improve outcomes over BCG/placebo. Favorable
      long-term survival among study patients suggests that metastasectomy should be
      considered for selected patients with stage IV melanoma.

PMID- 29019181
TI  - [Current status of bio-based materials industry in China].
AB  - In recent years, bio-based materials are becoming a new dominant industry leading
      the scientific and technological innovation, and economic development of the
      world. We reviewed the new development of bio-based materials industry in China,
      analyzed the entire market of bio-based materials products comprehensively, and
      also stated the industry status of bio-based chemicals, such as lactic acid, 1,3
      propanediol, and succinic acid; biodegradable bio-based polymers, such as co
      polyester of diacid and diol, polylactic acid, carbon dioxide based copolymer,
      polyhydroxyalknoates, polycaprolactone, and thermoplastic bio-based plastics; non
      biodegradable bio-based polymers, such as bio-based polyamide, polytrimethylene
      terephthalate, bio-based polyurethane, and bio-based fibers.

PMID- 29019182
TI  - [Progress on polyhydroxyalkanoates (PHA)].
AB  - Microbial polyhydroxyalkanoates (PHA) has developed with more diversity and more
      advanced manufacturing technology. Diversity has now been reflected by diverse
      monomers, diverse structures and diverse polymerization modes, giving the concept
      of "PHAome". In addition, the application of synthetic biology and the
      development of seawater-based biotechnology reduce the production cost of PHA,
      making PHA more economically competitive. Some examples of commercialized PHA
      products are described here. Besides, PHA with high value added applications has
      been exploited.

PMID- 29019183
TI  - [Biomanufactured polyhydroxyalkanoates (PHA) modification: a review].
AB  - In this review, we presented the industrial status of biomanufactured
      polyhydroxyalkanoates (PHA), including poly (3-hydroxybutyrate) (PHB), poly (3
      hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), poly (3-hydroxybutyrate-co-4
      hydroxybutyrate) (P3/4HB)), and poly (3-hydroxybutyrate-3-hydroxycaproate)
      (PHBH). A lot of modification studies, aimed at solving problems of poor thermal
      stability, narrow processing window and other drawbacks of PHA, are discussed.
      The properties of PHA can be optimized by using proper modification method, in
      order to expand its applications.

PMID- 29019184
TI  - [Application of biodegradable plastic film to reduce plastic film residual
      pollution in Chinese agriculture].
AB  - Plastic film has become an important agriculture production material in recent
      years. Over the past three decades, the amount and application area of plastic
      film have increased steadily, and in 2014, which are 1.4 million tons and more
      than 180 million hm2 respectively. It plays a key role for ensuring the supply of
      agricultural goods in China. Meanwhile, plastic film residual pollution becomes
      more and more serious, and in some regions, the amount of plastic film residues
      has reached over 250 kg/hm2. In part of the Northwest region, soil structure of
      farmland has been destroyed by plastic film residues and then crop growth and
      farming operations were suppressed. It is recognized as a good choice to replace
      plastic film with biodegradable plastic film, an effective measure to solve the
      plastic film residue pollution. Now, it is in a critical stage of study and
      assessment of biodegradable plastic film in China and fortunately some
      biodegradable plastic films show effects in the production of potatoes, peanuts
      and tobacco. Overall, a series of challenges has still been faced by the
      biodegradable plastic film, mainly including improving the quality of
      biodegradable plastic products, such as tensile strength, flexibility, improving
      the controllability of rupture and degradation, enhancing the ability of
      increasing soil temperature and preserving soil moisture, and to satisfy the
      demand of crops production with mulching. In addition, it is essential to reduce
      the cost of the biodegradable film and promote the application of biodegradable
      film on large-scale. With the development of biodegradable plastic technology and
      agricultural production environment, the application of the biodegradable film
      will have a good future.

PMID- 29019185
TI  - [Progress in bio-based polyamides].
AB  - Bio-based polyamides are environment-friendly polymers. The precursors of bio
      based polyamides come from bio-based materials such as castor oil, glucose and
      animal oil. Bio-based polyamides precursors include bio-based amino acids, bio
      based lactams, bio-based diprotic acid and bio-based diamines. In this paper, we
      discussed the route of the precursors of bio-based polyamides that come from bio
      based materials. We discussed the properties of bio-based polyamides. Bio-based
      PA11and bio-based PA1010 are well-known bio-based polyamides; we discussed the
      origin materials of the precursors, the route of manufacturing bio-based PA11 and
      PA1010, and their modifications status. The variety, classification and
      commercial production of bio-based polyamides were described in details, as well
      as bio-based polyamides development in China.

PMID- 29019186
TI  - [Development and perspective of bio-based chemical fiber industry].
AB  - Bio-based fiber is environment friendly, reproducible, easily biodegradable.
      Therefore, rapid development of bio-based fiber industry is an obvious in
      progress to replace petrochemical resources, develop sustainable economy, build
      resource saving and environment friendly society. This article describes the
      current development of bio-based fiber industry, analyzes existing problems,
      indicates the trends and objectives of bio-based fiber materials technology
      innovation and recommends developing bio-based fibers industry of our country.

PMID- 29019187
TI  - [Processing, properties and application of poly lactic acid (PLA) fiber].
AB  - Poly lactic acid (PLA) fibers a biodegradable fiber produced from PLA resin by
      melt spinning, solvent spinning or electrostatic spinning. Based on the excellent
      safety, comfortability, environmental protection and good mechanical properties,
      PLA can be widely applied in textile fabric, nonwoven, filler fabric and many
      downstream health products application, such as sanitary napkins, baby diapers,
      facial masks, and wipes.

PMID- 29019188
TI  - [Recent advances in nucleating agents used for poly (lactic acid)].
AB  - Poly (lactic acid) (PLA) is a polymer synthesized from lactic acid with good
      biocompatibility and biodegradability. At present, PLA manufactured on industrial
      scale is mainly synthesized from L-lactic acid. The obtained products have good
      transparency but poor heat resistance. Adding nucleating agents could increase
      the crystallinity of PLA, to improve heat resistance. We reviewed the progress of
      research on organic and inorganic nucleating agents that can be used for PLA
      synthesis.

PMID- 29019189
TI  - [Improved protein-A chromatography for monoclonal antibody purification].
AB  - Therapeutic monoclonal antibodies become the major product class within the
      biopharmaceutical market. Protein A as the first capture step is still dominant
      in current platforms for purification of monoclonal antibodies. In this study, we
      developed a new antibody harvest process that incorporates acidic treatment of
      cell harvest, demonstrating high process yield, improved clearance of host cell
      associated contaminants, like non-histone host cell protein, histone, DNA and
      heteroaggregates. Host protein contamination was reduced about 10-fold compared
      to protein A loaded with harvest clarified by centrifugation and microfiltration.
      Turbidity increase of eluted IgG upon pH neutralization was nearly eliminated.
      Residual levels of impurities in the protein A eluate were achieved that
      potentially meet requirements of drug substance and thus alleviate the burden for
      further impurities removal in subsequent chromatography steps. The mechanism of
      host cell associated contaminants removal during acidic treatment was also
      explored. After a polishing step by Capto adhere, host cell protein was reduced
      to less than 5 ppm, DNA less than 1 ppb, histone to undetectable level,
      heteroaggregates less than 0.01% with total IgG recovery around 87%. This
      efficient process can be easily integrated into current IgG purification
      platforms, and may overcome downstream processing challenges.

PMID- 29019190
TI  - [Isolation, purification of collagen from soft-shelled turtle calipash for
      application in biomaterial].
AB  - Recently, research on collagen attracts more interests due to its good biological
      compatibility. The present study attempted to establish a fast and efficient
      method to purify collagen from soft-shelled turtle and to explore its application
      in biological materials. The structure and type of collagen fiber in calipash
      were determined by van Gieson staining and Picrosirius red staining, which could
      contribute to the isolation of collagen from soft-shelled turtle Calipash (STCC).
      Collagen fibers were in high content and the main collagen fiber was type I in
      STCC. The crude STCC solution was purified by dialysis with different cut-off
      molecular weight. SDS-PAGE demonstrated that the best purification was in
      applying 100 kDa dialysis bags after 48 h. The water absorbing capacity and
      holding capacity of STCC were up to 12.06 g/g and 98.21%, respectively. STCC can
      be degraded by collagenase in vitro entirely after 72 h. The hemolysis, skin
      sensitization, hemostatic and wound healing of STCC were determined by using SD
      rat model, and the collagen cross-linked by glutaric dialdehyde was set as a
      comparison. STCC and STCC cross-linked did not result in destructed red blood
      cell, inflamed and sensitized skin. Both materials exhibited good hemostatic
      effect. Thus, STCC improved the wound healing efficiently. This study implies a
      potential of STCC in the field of biomaterial.

PMID- 29019191
TI  - [Synthesis and characterization of polylactide-based thermosetting polyurethanes
      with shape memory properties].
AB  - A series of bio-based thermosetting polyurethanes (Bio-PUs) were synthesized by
      the crosslinking reaction of polylactide and its copolymers diols with
      hexamethylene diisocyanate (HDI) trimer. The obtained Bio-PUs were characterized
      by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning
      Calorimetry (DSC), Thermal Gravimetric Analysis (TGA), universal tensile testing
      machine and cytotoxicity test. Results indicate that the PLA copolymer (P(LA-co
      CL)) diols reduced the glass transition temperature (Tg) of Bio-PUs and improved
      their thermal stability, compared with PLA diols. The Bio-PUs synthesized from P
      (LA-co-CL) diols exhibit better mechanical performance and shape memory
      properties. Especially, Young modulus and elongation at break of the obtained Bio
      PUs were 277.7 MPa and 230% respectively; the shape recovery time of the obtained
      Bio-PUs at body temperature was only 93 s. Furthermore, alamar blue assay results
      showed that the obtained Bio-PUs had no cell toxicity.

PMID- 29019192
TI  - [Effect of glyceryl triacetate on properties of PLA/PBAT blends].
AB  - Poly lactic acid (PLA)/Poly (butyleneadipate-co-terephthalate)(PBAT) and glyceryl
      triacetate (GTA) blend were prepared by torque rheometer, and the effect of GTA
      on thermodynamical performance, mechanical properties and microstructure of
      PLA/PBAT composites were studied using differential scanning calorimeter(DSC),
      dynamic mechanical analysis(DMA), universal testing machine, impact testing
      machine and scanning electron microscope(SEM). After adding GTA, Tg values of the
      two phases gradually became closer, blends cold crystallization temperature and
      melting temperature decreased. When with 3 phr GTA, the dispersed phase particle
      size of PLA/PBAT blend decreased. Mechanics performance test showed that the
      elongation at break and impact strength of the PLA/PBAT blend was greatly
      increased with 3 phr GTA, and the elongation at break increased 2.6 times,
      improved from 17.7% to 64.1%.

PMID- 29019193
TI  - [Advances in stress response of DNA binding with one finger transcription factor
      family genes in graminaceous plants].
AB  - Transcription factor is a key trans-acting factor to mediate stress response by
      regulating gene expression. Plants have developed a series of mechanisms to
      modulate development, stress response, signaling and disease resistance at
      transcription level. DNA binding with one finger (DOF), containing one C2-C2 zinc
      finger domain, is a special plant transcription factor. Specifically, the
      conserved domain at N-terminus of DOF has multiple functions, including
      interacting with DNA and protein, which could be involved in plant development
      and stress response. Although many DOF family genes are characterized in plant
      stress response, it is not clear if DOF genes have functions in cereal plants. In
      the present paper, the role of DOF family genes on cereal plants were discussed
      based on a comprehensive phylogenetic relationship analysis, expression profiles
      in different tissues and various environmental conditions. The results obtained
      here will provide an important reference for further understanding the mechanism
      of gramineous crops in stress resistance.

PMID- 29019194
TI  - [Research progress in hydroxylase in taxol biosynthetic pathway].
AB  - Taxol is a secondary metabolite with prominent anti-tumor activity, but the yield
      cannot meet the growing clinical demand due to lower content in yew. Now, most
      enzyme genes involved in taxol biosynthesis have been cloned and identified, so
      that obtaining this drug by using synthetic biology method has become a hotspot
      in recent years. However, most hydroxylases involved in taxol biosynthetic
      pathway have not been explored. Here, we reviewed the progress on the
      biosynthesis pathway of taxol, especially concerning hydroxylase. The future
      research areas of taxol biosynthesis through synthetic biology were also
      discussed to provide basis for the discovery of uncharacterized hydroxylase genes
      and the mass taxol production by synthetic biology technology.

PMID- 29019195
TI  - [Advances in tumor-therapy using genetically modified Salmonella].
AB  - Tumor is a neoplasm formed by the abnormal proliferation of local tissue cells
      under the effects of different tumorigenic factors. Tumor-therapy has always been
      a difficult clinical issue, while regular cancer treatments, such as
      radiotherapy, chemotherapy and surgery, have obvious limitations. Earlier studies
      have shown that some obligate anaerobes or facultative anaerobes have anti-tumor
      effects, for example, Salmonella typhymurium as facultative anaerobic bacteria
      can selectively colonize tumors and inhibit their growth. Besides, Salmonella has
      many advantages in tumor-therapy. In the past decade or two, many researchers
      have carried out genetic manipulation to attenuate the virulence of Salmonella,
      to improve their specificity of tumor colonization and specially to use
      attenuated Salmonella as carriers to deliver a variety of anti-tumor therapeutic
      molecules, and these genetically modified Salmonella have shown good anti-tumor
      effects in many animal experiments. Along with further research of Salmonella
      mediated antitumor treatment, applications of genetically modified Salmonella for
      more effective tumor-therapy are promising. We reviewed the anti-tumor mechanisms
      of Salmonella, the research progress in tumor-therapy using genetically modified
      Salmonella, and current problems and possible solutions.

PMID- 29019196
TI  - [Prokaryotic expression and immunogenicity of IgG-binding protein of
      Streptococcus equi subspecies equi].
AB  - To analyze the immunogenicity and protective ability of recombinant IgG-binding
      protein (EAG) of Streptococcus equi subspecies equi and to evaluate its value
      when used as equine vaccine antigen, EAG gene was amplified by PCR and inserted
      into pET-28a vector. The EAG recombinant proteins were expressed and purified to
      immune mice. The serum antibody and challenge protection were tested. The
      purified recombinant protein of EAG was 26 kDa, and the protein reacted
      specifically with positive serum of Streptococcus equi subspecies equi. The mice
      antibody level for EAG immunization group was 1?8 100. The immunological
      protection result showed that the protection rate of the EAG recombinant protein
      was 90%. The results suggested that the EAG protein has good immunogenicity and
      immunological protection, and it can effectively increase the humoral immune
      response and immunological protection of mice.

PMID- 29019197
TI  - [Transcriptome analysis of Pichia pastoris in response to ethanol stress].
AB  - Effective expression of pIFN-alpha in recombinant Pichia pastoris was conducted
      in a 5 L fermentor. Ethanol accumulation during the late glycerol feeding period
      inhibited heterologous protein expression. Comparative transcriptome analysis was
      thus performed to compare the gene transcription profiles of Pichia pastoris
      KM71H in high and low ethanol concentration environments. The results showed that
      during the glycerol cultivation stage, 545 genes (265 up-regulated and 280 down
      regulated) were differentially expressed with ethanol stress. These genes were
      mainly involved in protein synthesis, energy metabolism, cell cycle and
      peroxisome metabolism. During the methanol induction stage, 294 genes (171 up
      regulated and 123 down-regulated) were differentially expressed, which were
      mainly related to methanol metabolism, amino acid metabolism and protein
      synthesis. Ethanol stress increased protein misfolding and reduced structural
      integrity of ribosome and mitochondria during cultivation stage, and led to the
      failure of endoplasmic reticulum stress removal and damaged amino acid metabolism
      during induction stage in Pichia pastoris.

PMID- 29019198
TI  - [Isolation, identification and structural characterization of secondary
      metabolites from amarine sponge-derived rare actinobacterium Dermacoccus sp. X4].
AB  - We isolated and identified the symbiotic and adnascent microorganisms from an
      unidentified sponge collected from 10-meter-deep seawater of the Paracel Islands
      in China. A total of 16 strains were obtained and identified. Through
      bacteriostatic activity assay, one of the strains, Dermacoccus sp. X4, was found
      to effectively inhibit the growth of Staphylococcus aureus. Subsequently, its
      secondary metabolites were purified by silica gel partition, octadecylsilane
      (ODS) reverse phase, SephadexTMLH-20 size exclusion, and C18 reverse phase
      chromatography. Using liquid chromatography, mass spectrometry, and nuclear
      magnetic resonance, three of the purified compounds were structurally
      characterized to be one 3-(4-hydroxybenzyl) hexahydropyrrolo [1,2-a]pyrazine-1,4
      dione and two indole acid glycerides. This is the first report about indole acid
      glyceride isolated from microbial secondary metabolites, enriching marine drug
      candidate resources.

PMID- 29019199
TI  - [Molecular cloning, in vitro expression and bioactivity of TRAIL (TNFSF10) gene
      from finless porpoises].
AB  - To construct soluble TNF related apoptosis inducing ligand (TRAIL) expression
      system and investigate the effect of the expression product on tumor cell. It may
      provide valuable information for research into the immune system of the finless
      porpoise. The full-length cDNA of TRAIL (designated fTRAIL) was cloned from the
      total RNA of the finless porpoises blood using RT-PCR techniques and then the
      extracellular soluble fragments of fTRAIL (designated fsTRAIL) was ligated into
      pET43.1a. Recombinant soluble fTRAIL (pET43.1a-fsTRAIL) fused with Nus-his tag
      was efficiently expressed in Escherichia coli BL21 (DE3) and the Nus-His-fsTRAIL
      protein was purified. The expression of Nus-His-fsTRAIL was verified by Western
      blotting. In vitro, the effects of the purified Nus-His-fsTRAIL protein on Jurkat
      and HeLa cells were etected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrasodium bromide (MTT) assay, TrypanBlue and Flow Cytometry analysis. The
      expression system pET43.1a-fsTRAIL was constructed and Nus-His-fsTRAIL protein
      was expressed successfully. In vitro, the Nus-His-fsTRAIL protein was able to
      inhibit the proliferation and induce apoptosis of Jurkat and HeLa cells in a dose
      dependent manner. The Nus-His-fsTRAIL protein has anti-tumor activity against
      Jurkat and HeLa cells in vitro.

PMID- 29019200
TI  - [Effects of copper on biodegradation mechanism of trichloroethylene by mixed
      microorganisms].
AB  - We isolated and enriched mixed microorganisms SWA1 from landfill cover soils
      supplemented with trichloroethylene (TCE). The microbial mixture could degrade
      TCE effectively under aerobic conditions. Then, we investigated the effect of
      copper ion (0 to 15 MUmol/L) on TCE biodegradation. Results show that the maximum
      TCE degradation speed was 29.60 nmol/min with 95.75% degradation when copper ion
      was at 0.03 MUmol/L. In addition, genes encoding key enzymes during
      biodegradation were analyzed by Real-time quantitative reverse transcription PCR
      (RT-qPCR). The relative expression abundance of pmoA gene (4.22E-03) and mmoX
      gene (9.30E-06) was the highest when copper ion was at 0.03 MUmol/L. Finally, we
      also used MiSeq pyrosequencing to investigate the diversity of microbial
      community. Methylocystaceae that can co-metabolic degrade TCE were the dominant
      microorganisms; other microorganisms with the function of direct oxidation of TCE
      were also included in SWA1 and the microbial diversity decreased significantly
      along with increasing of copper ion concentration. Based on the above results,
      variation of copper ion concentration affected the composition of SWA1 and
      degradation mechanism of TCE. The degradation mechanism of TCE included co
      metabolism degradation of methanotrophs and oxidation metabolism directly at
      copper ion of 0.03 MUmol/L. When copper ion at 5 MUmol/L (biodegradation was
      84.75%), the degradation mechanism of TCE included direct-degradation and co
      metabolism degradation of methanotrophs and microorganisms containing phenol
      hydroxylase. Therefore, biodegradation of TCE by microorganisms was a complicated
      process, the degradation mechanism included co-metabolism degradation of
      methanotrophs and bio-oxidation of non-methanotrophs.

PMID- 29019202
TI  - [Structure and immunomodulatory activity of extracellular polysaccharide from
      Grifola frondosa].
AB  - We aimed at analyzing the structure of extracellular polysaccharide A from
      Grifola frondosa (EXGFP-A) and testing its immunomodulatory activity. Structural
      analysis shows that EXGFP-A was a contained alpha-D-glucoside bond and pyranose
      ring. GC analysis reveals that EXGFP-A was mainly composed of rhamnose,
      arabinose, xylose, mannose, glucose, galactose, by the molar ratio of
      0.28:0.31:0.30:0.06:7.98:0.61. The results of MTT(3-(4,5-Dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide) assay indicates when EXGFP-A was at a
      concentration of 80 MUg/mL and treatment time of 48 h, RAW264.7 cells
      proliferation index reached a maximum of 137.5%. Meanwhile, the AO staining
      showed that EXGFP-A activated RAW264.7 cells and improved the level of
      intracellular nucleic acid metabolism. In addition, in a certain range of
      concentration, EXGFP-A was able to increase the release of NO in RAW264.7 cells,
      and upregulate the mRNA expression of immunological factor TNF-alpha, IL-1beta,
      IL-6, IL-12, IFN-gamma and iNOS of RAW264.7 cells. Our results confirm that EXGFP
      A had immunomodulatory activity. Our findings provided scientific basis for the
      structural analysis and application of Grifola frondosa polysaccharide.

PMID- 29019201
TI  - [Cloning and expression profile of Bmlin-41 and its regulation by the silkworm
      microRNA let-7].
AB  - The heterochronic genes regulate cell proliferation and switch development stage
      transitions. Heterochronic genes might also play important roles in regulating
      the development of silkworm, but very few of their expression profiles, functions
      and their relationship with microRNAs are available so far. Firstly, in this
      work, the primers for cloning Bmlin-41 were designed based on the homologous
      sequence of known Drosophila melanogaster lin-41, which was used as the query to
      blast against SilkDB. The obtained full CDS (2 166 bp) of Bmlin-41 encodes 721
      amino acids and contains B-box and NHL domains. Then, the spatiotemporal
      expression patterns of Bmlin-41 were characterized by RT-PCR, quantitative real
      time PCR as well as our lab's previous silkworm genome microarray data. Bmlin-41
      was increasingly expressed from embryonic to adult stage. In diverse tissues of
      day-3 fifth instar, Bmlin-41 showed the highest accumulation in ovary, secondly
      in testis and midgut, but very low expression was observed in other tissues.
      Finally, 3'UTR of Bmlin-41 1 434 bp was cloned by rapid-amplification of cDNA
      ends (3'RACE) and was predicted to bare two binding sites of bmo-let-7 by using
      online RNAhybrid. To verify the binding effect, 3'UTR was cloned into psi-CHECK-2
      vector and submitted to dual luciferase assay in the S2 cells in vitro. The dual
      luciferase assay demonstrated that Bmlin-41 was down-regulated by bmo-let-7
      mimics and upregulated by bmo-let-7 antagomir, thus confirming the Bmlin-41 is
      negatively regulated by bmo-let-7. Our work might help further study on the roles
      of Bmlin-41 and bmo-let-7 and their regulation relationship involved in
      controlling metamorphosis of silkworm.

PMID- 29019203
TI  - [Analysis of exogenous gene and protein digestion and absorption of SD rats
      (Rattus norvegicus) fed roundup ready soybean meal].
AB  - Metabolism and deposition of exogenous gene and protein from transgenic
      glyphosate herbicide-tolerant soybean meal in SD rats were studied in the
      experiment. The transgenic soybean GTS40-3-2 meal and its non-transgenic
      counterpart (parent A5403) were fed to the generation and the second generation
      Sprague-Dawley (SD) rats (Rattus norvegicus). The study added the genetically
      modified (GM) soybean meal and its non-transgenic control soybean meal (parent
      A5403) in a ratio of 20% respectively to the feeds. By using qualitative,
      quantitative PCR and ELISA methods to detect transgenic soybean residues of
      metabolism ingredients in rats, the safety and influence of GM soybean were
      evaluated. The results showed that the intestinal fecal and cecum contents of
      rats were detected with residues of GM ingredients, intestinal flora and organs
      were not found related genes and protein. These results indicated that transgenic
      glyphosate herbicide-tolerant soybean GTS40-3-2 meal was as safe as its non-GM
      soybean meal in long-term feeding study.

PMID- 29019204
TI  - [Molecular recognition mechanism and motion of HCV NS3/4A protease with
      Faldaprevir analogue].
AB  - Faldaprevir analogue molecule (FAM) has been reported to effectively inhibit the
      catalytic activity of HCV NS3/4A protease, making it a potential lead compound
      against HCV. A series of HCV NS3/4A protease crystal structures were analyzed by
      bioinformatics methods, and the FAM-HCV NS3/4A protease crystal structure was
      chosen for this study. A 20.4 ns molecular dynamics simulation of the complex
      consists of HCV NS3/4A protease and FAM was conducted. The key amino acid
      residues for interaction and the binding driving force for the molecular
      recognition between the protease and FAM were identified from the hydrogen bonds
      and binding free energy analyses. With the driving force of hydrogen bonds and
      van der Waals, FAM specifically bind to the active pocket of HCV NS3/4A protease,
      including V130-S137, F152-D166, D77-D79 and V55, which agreed with the
      experimental data. The effect of R155K, D168E/V and V170T site-directed
      mutagenesis on FAM molecular recognition was analyzed for their effect on drug
      resistance, which provided the possible molecular explanation of FAM resistance.
      Finally, the system conformational change was explored by using free energy
      landscape and conformational cluster. The result showed four kinds of dominant
      conformation, which provides theoretical basis for subsequent design of
      Faldaprevir analogue inhibitors based on the structure of HCV NS3/4A protease.

PMID- 29019205
TI  - [Construction and characterization of an attenuated recombinant Listeria
      monocytogenes vector vaccine delivering HPV16 E7].
AB  - Listeria monocytogenes (L. monocytogenes, LM) is an excellent tumor vaccine
      vector. In this study, recombinant LM vaccine candidate expressing human
      papillomavirus type 16 (HPV16) E7 protein was constructed and its charactericts
      were determined. Through homologous recombination, E7 gene was cloned in frame
      with the LM4 Phly promoter-signal sequence, and introduced into the chromosome of
      LM4. The recombinant strain named LM4?hly::E7 with the plasmid-free and
      antibiotic-resistant gene-free was constructed. LM4?hly::E7 could express and
      secrete E7-LLO fusion protein; its size is 66 kDa and has immunological activity.
      Furthermore, LM4?hly::E7 could multiply in RAW264.7 macrophages by confocal laser
      scanning microscope. Additionally, LM4?hly::E7 could induce specific antibodies
      against E7 in immunized mice in ELISA. Also, the 50% lethal dose (LD50) of
      LM4?hly::E7 strain was 3.863*109 CFU (Colony-Forming Units) in C57BL/6 mice with
      intraperitoneal immunization, which was more attenuated than wild type LM4. Mice
      immunized with LM4?hly::E7 did not show obvious pathological change. These data
      show that LM4?hly::E7 expressing E7-LLO fusion protein has good safety, which may
      provide the materials for research of antitumor effect and would be a promising
      vaccine candidate for cervical cancer.

PMID- 29019206
TI  - [Bioinformatics analysis of sequence and structure of insulin-like growth factor
      I receptor].
AB  - The length of IGF1R 3'UTR is greater than 7 kb. The structure of IGF1R 3'UTR is
      complex, with multiple binding sites of miRNAs. IGF1R is involved in the
      regulation of MAPK and PI3K/AKT signaling pathways and theformation and
      development of tumors. Bioinformatics analysis can reveal the structure features
      of IGF1R, which provides ideas for further research. The analysis shows that the
      binding sites between IGF1R and miRNAs have the highest mutation rate in
      Neuroblastoma. We analyzed the structure of 3'UTR, miRNAs binding sites, physical
      and chemical properties, hydrophilic-hydrophobic property, glycosylation and
      phosphorylation sites, secondary structure and tertiary structure modeling of
      IGF1R. The locations and names of amino acids interacting in IGF1R and IGF1 were
      obtained by molecular docking. Therefore, if IGF1R 3'UTR is mutated, the capacity
      of IGF1R combined with miRNAs will reduce and the IGF1R expression will be up
      regulated, and the function of miRNAs will be repressed. We can change the sites
      of IGF1R to combine with IGF1 to repress the function of IGF1R and IGF1. Then the
      function of IGF1R will be repressed.

PMID- 29019207
TI  - [Retrospect and prospect of transgenic fish breeding in China].
AB  - The first transgenic fish was generated in China about 30 years ago. Since then,
      considerable progress has been achieved for farmed fishes breeding with
      improvement of target traits of growth, disease resistance, stress tolerance, and
      nutrition qualities. Up to now, the technology of transgenic fish breeding is
      almost mature and the biosafety assessment is established. In this review, a
      successful example of the fast-growing transgenic common carp was presented and
      the foreground of transgenic fish breeding was also discussed and prospected.

PMID- 29019208
TI  - [Research progress of CRISPR-Cas9 system for gene therapy].
AB  - The clustered regulatory interspaced short palindromic repeat-Cas9 (CRISPR-Cas9)
      system is the part of the prokaryotic immune system, which could recognize and
      delete the exogenous sequences originated from virus or plasmid. Based on its
      mechanism, CRISPR-Cas9 system was developed into the new generation of gene
      editing tool. Compared to the existed technologies such as ES targeting, ZFN or
      TALEN, CRISPR-Cas9 system is a more efficient, economical and promising approach
      to manipulate the genome. In this review, we summarize the research progress
      about CRISPR-Cas9 technology, especially the latest applications in gene therapy
      studies of human diseases.

PMID- 29019209
TI  - [Function of SIRT6 in tumor initiation and progression].
AB  - As a member of the sirtuins family, also called Class III histone deacetylases
      (HDACs), SIRT6 has many catalytic enzyme activities and plays a pivotal role in
      biological processes including anti-aging, chromatin regulation, transcriptional
      control, glucose and lipid metabolism, and DNA damage repair. Recently,
      increasing evidences indicated that SIRT6 was related to initiation and
      development of tumors, such as hepatic cancer, lung cancer, breast cancer and
      genital system tumors. However, SIRT6 might play a dual role in tumorigenesis and
      progression. SIRT6 often acted as a tumor suppressor, but might play an oncogenic
      role. Based on our current study, we depicted the essential roles of SIRT6 in the
      initiation and progression of various tumors, and summarized its mode of actions,
      which might provide clues for cancer therapy.

PMID- 29019210
TI  - [Progress on cellulosic ethanol produced from beet pulp].
AB  - Cellulosic ethanol, with the advantages of renewable resource, cleanliness and
      safety, is the mainstream of new energy development and has obtained extensive
      attention worldwide. In this review, the biological characteristics of beets were
      introduced, and then the superiority and application progress of beets and its by
      product sugar beet pulp in the bioethanol production were stated. At last,
      cellulosic ethanol production coupled with the component separation and
      comprehensive utilization of beet pulp was proposed.

PMID- 29019211
TI  - [Cloning, eukaryotic expressing and function analysis of Schistosoma japonicum
      apoptosis gene Sjcaspase3].
AB  - For further research of the apoptosis mechanism of Schistosoma japonicum (S.
      japonicum). The cDNA encoding Sjcaspase3 of Schistosoma japonicum was amplified
      by polymerase chain reaction (PCR) technique, which contained 900 nucleotides and
      encoded 299 amino acids. The theory molecular weight and isoelectric point (PI)
      of the deduced protein is 33.5 kDa and 6.39, respectively. Real-time PCR was used
      to analyze the transcription profiles of Sjcaspase3 at different development
      stages of S. japonicum. The results showed that this gene was expressed in all
      stages of S. japonicum with the highest expression in 21d worms, and the level of
      gene transcription in 42 d female worms was higher than that of male worms. The
      recombinant plasmid pXJ40-FLAG-Sjcaspase3 was constructed and transfection into
      Hela cells successfully. Real-time PCR and Western blotting analysis showed
      Sjcaspase3 was successfully expressed in Hela cells. Enzyme activity analysis
      revealed that recombinant Sjcaspase3 possessed the activity to cut substrate
      DEVD. Flow cytometry proved that Sjcaspase3 could induce early apoptosis of Hela
      cells. The results provide the basis for proceeding further study on the
      biological function of Sjcaspase3 and better understand the apoptosis mechanism
      of S. japonicum.

PMID- 29019212
TI  - [Effect of integration loci of genome on heterologous gene expression in
      Saccharomyces cerevisiae].
AB  - Chromosomal integration of heterologous genes or pathways is preferred over the
      use of episomal plasmids for its inherently stability and thus more desirable in
      the industrial setting. However, the position of integration of heterologous
      genes in the genome influences the expression levels. In combination of high
      throughput transformation of the Yeast Knock-out Collection (YKO) and FACS
      analysis, the position effect on heterologous reporter gene gfp was identified
      across the whole genome in yeast. In total 428 high-expressed sites and 444 low
      expressed sites were spotted, providing massive data to analyze patterns and
      reasons for region dependency of gene expression on the genome-wide scale.

PMID- 29019213
TI  - [Expression and characterization of a novel omega-transaminase from Burkholderia
      phytofirmans PsJN].
AB  - Production of chiral amines and unnatural amino-acid using omega-transaminase can
      be achieved by kinetic resolution and asymmetric synthesis, thus omega
      transaminase is of great importance in the synthesis of pharmaceutical
      intermediates. By genomic data mining, a putative omega-transaminase gene hbp was
      found in Burkholderia phytofirmans PsJN. The gene was cloned and over-expressed
      in Escherichia coli BL21 (DE3). The recombinant enzyme (HBP) was purified by Ni
      NTA column and its catalytic properties and substrate profile were studied. HBP
      showed high relative activity (33.80 U/mg) and enantioselectivity toward beta
      phenylalanine (beta-Phe). The optimal reaction temperature and pH were 40 C and
      8.0-8.5, respectively. We also established a simpler and more effective method to
      detect the deamination reaction of beta-Phe by UV absorption method using
      microplate reader, and demonstrated the thermodynamic property of this reaction.
      The substrate profiling showed that HBP was specific to beta-Phe and its
      derivatives as the amino donor. HBP catalyzed the resolution of rac-beta-Phe and
      its derivatives, the products (R)-amino acids were obtained with about 50%
      conversions and 99% ee.

PMID- 29019214
TI  - [Molecular characteristics of two Phi glutathione S-transferases in Selaginella
      moellendorffii].
AB  - Glutathione S-transferase (GST) is important in plants to resist various
      stresses. In this study, two Phi GST genes (SmGSTF1 and SmGSTF2) were cloned from
      Selaginella moellendorffii. SmGSTF1 and SmGSTF2 genes encode proteins of 215
      amino acid residues. Gene expression analysis showed that the two genes were
      expressed in roots, stems and leaves. The recombinant SmGSTF1 and SmGSTF2
      proteins were overexpressed in Escherichia coli, and purified by Ni-affinity
      chromatography. SmGSTF1 and SmGSTF2 had the catalytic activity towards 1-Chloro
      2,4-Dieitrobenzene, 4-Chloro-7-nitro-1,2,3-benzoxadiazole (NBD-Cl), and 4
      Nitrobenzyl chloride substrates. SmGSTF1 also had the activity towards
      Fluorodifen and Cumyl hydroperoxide (Cum-OOH), whereas SmGSTF2 not. The enzyme
      kinetics analysis showed that SmGSTF1 and SmGSTF2 had high affinity towards
      glutathione, and low affinity towards 1-Chloro-2, 4-Dieitrobenzene. The enzymatic
      activity of SmGSTF1 and SmGSTF2 had high catalytic activity between pH 7 and 8.5,
      and between 45 and 55  degrees C. SmGSTF1 and SmGSTF2 may have an important role
      in the resistance of Selaginella moellendorfii against stress.

PMID- 29019215
TI  - [Global proteomic and phosphoproteomic analysis of the premature maize anther].
AB  - Reversible phosphorylation plays a crucial role in regulating protein activities
      and functions. Sexual reproduction directly affects yield of most agricultural
      crops. As the male reproductive organ, anther generates microspores (pollen),
      delivering gametes (sperms) to complete double fertilization in higher plants.
      Here, we took the advantage of Nano UHPLC-MS/MS to analyze maize (Zea mays, B73)
      early anthers at proteomic and phosphoproteomic levels, to explore the protein
      and phosphorylation modification regulatory networks controlling maize anther
      development. Our proteomic analysis identified 3 016 unique peptides, belonging
      to 1 032 maize proteins. MapMan analysis revealed variously potential proteins
      associated with maize anther development, such as receptor-like kinases
      (GRMZM2G082823_P01 and GRMZM5G805485_P01). Using phospho-peptides enriched by
      TiO2 affinity chromatography, our phosphoproteomic analysis detected 257 phospho
      peptides from 210 phosphoproteins, discovering 223 phosphosites. Compared to the
      86 maize phosphoproteins collected in the Plant Protein Phosphorylation Data Base
      (P3DB), we found that 203 phosphoproteins and 218 phosphosites were not revealed
      before. Further bioinformatics analysis revealed that phosphorylation of 14-3-3
      proteins, kinases, phosphatases, transcription factors, cell cycle and chromatin
      structure related proteins might play important roles in regulating normal anther
      development in maize. Our findings not only enlarged the maize phosphoproteome
      data, but also provided information for analyzing the molecular mechanism
      controlling maize anther development at genetic and biochemical levels.

PMID- 29019216
TI  - [An XcmI-generated T vector and its applications in synthetic biology].
AB  - For more economical and efficient DNA clonging, pFL-XS-T, a Biobrick-T vector was
      constructed based on pMD18-T vector, carrying clonging regions of XbaI-XcmI-XcmI
      SpeI. The results revealed that PCR products could be conveniently inserted into
      pFL-XS-T vevtor digested by XcmIby means of TA cloning. The positive frequency of
      recombination can meet the experimental requirements and all the plasmids
      obtained meet Biobrick standard. Moreover, the pFL-XS-T is compatible with other
      Biobrick parts, and serves as a vector for functional DNA fragments screening.

PMID- 29019217
TI  - [Screening specific recognition motif of RNA-binding proteins by SELEX in
      combination with next-generation sequencing technique].
AB  - RNA-binding protein exerts important biological function by specifically
      recognizing RNA motif. SELEX (Systematic evolution of ligands by exponential
      enrichment), an in vitro selection method, can obtain consensus motif with high
      affinity and specificity for many target molecules from DNA or RNA libraries.
      Here, we combined SELEX with next-generation sequencing to study the protein-RNA
      interaction in vitro. A pool of RNAs with 20 bp random sequences were transcribed
      by T7 promoter, and target protein was inserted into plasmid containing SBP-tag,
      which can be captured by streptavidin beads. Through only one cycle, the specific
      RNA motif can be obtained, which dramatically improved the selection efficiency.
      Using this method, we found that human hnRNP A1 RRMs domain (UP1 domain) bound
      RNA motifs containing AGG and AG sequences. The EMSA experiment indicated that
      hnRNP A1 RRMs could bind the obtained RNA motif. Taken together, this method
      provides a rapid and effective method to study the RNA binding specificity of
      proteins.

PMID- 29019218
TI  - [In vitro development and chimeric efficiency of mouse-porcine interspecies
      chimeric embryos in different culture systems].
AB  - With the advancements of stem cells and regenerative medicine, interspecies
      chimera has become a hot topic and will pave a new way of providing donor sources
      in organ transplantation. However, the interspecies chimera is confronted with a
      number of scientific questions and technical obstacles, including selections of
      appropriate embryonic stage and appropriate culture medium; those factors will
      deeply influence the developmental balance between donor cells and receptor
      embryos. Due to its relatively rapid reproductive cycle and similar organ size to
      human's, porcine is a very potential donor candidate to study these questions. To
      compare the development and chimeric efficiency of interspecies embryos, we
      tested and evaluated three different culture systems, PZM-3 (Porcine zygotic
      medium), culture medium for iPSCs (N2B27) and 3.5 h of N2B27 before PZM-3
      (N2B27(3.5 h)), and two different embryonic stages, 8-cell and blastocyst in
      mouse-porcine chimeric embryos using parthenogenetically activated porcine
      embryos and mouse induced pluripotent stem cells (miPS). The results showed that,
      PZM-3 was beneficial for both development of chimeric embryos and miPSCs
      proliferation in porcine embryos in the 8-cell injection group. After early
      blastocyst injection, the chimeric efficiency did not appear significantly
      different among the three culture systems but was lower than 8-cell injection. In
      summary, the results suggest that 8-cell injection and PZM-3 culture medium are
      more beneficial to the in vitro development and chimeric efficiency of mouse
      porcine chimeric embryos.

PMID- 29019219
TI  - [High-level production of glucose oxidase by recombinant Pichia pastoris using a
      combined strategy].
AB  - To enhance the production of glucose oxidase by recombinant Pichia pastoris, two
      strategies were developed, which were namely co-feeding of methanol and sorbitol
      and co-expressing of the protein disulfide isomerase (PDI) and Vitreoscialla
      hemoglobin (VHb). The volumetric activity reached 456 U/mL by using the strain
      X33/pPIC9k-GOD, in 5 liter fermentator, with the co-feeding of methanol and
      sorbitol, it was 0.2 fold higher than that only feeding by methanol. The improved
      strain was obtained by co-expressing PDI-VHb with GOD. While fermented in a 5
      liter fermentator by feeding methanol and sorbitol, the activity of the improved
      strain reached 716 U/mL with a yield of 7 400 mg/L total soluble protein
      concentration. These results indicated that heterologous protein expression level
      can be enhanced by optimizing fermentation condition and co-expression molecular
      chaperon in Pichia pastoris.

PMID- 29019220
TI  - [Secretory expression and characterization of heat sensitive nuclease in Pichia
      pastoris].
AB  - Nucleases is an important enzyme widely used in biotechnology. A codon optimized
      nuclease gene (SNU) from Northern Shrimps was inserted into pPICZalpha A vector,
      and expressed extracellularly in strain SMD1168H. On the basis of multi-copy
      recombinant strain, we further optimized the expression condition and
      characterized SNU. SNU was highly expressed and stable after 1% methanol
      induction for 72 h, yield reached 1.4*105 U/mL. SDS-PAGE electrophoresis
      demonstrated that this is a N-linked glycoprotein of 50 kDa. It was purified by
      one step DEAE Sephadex chromatography to the purity of about 15 mg/L with a
      specific activity of 6.291*106 U/mg. Functional analysis on the nuclease activity
      indicated that it was stimulated by bivalent iron, such as Ca2+, Mn2+, Co2+ and
      Mg2+, but inhibited by Zn2+, Cu2+ and high salt. Meanwhile, it was irreversibly
      inactivated at 70 C for 10 min.

PMID- 29019221
TI  - [Traditional Chinese Medicine promotes the development of andrology].
AB  - Andrology is an ancient branch of science which has gained a new development in
      the recent years and therefore has both traditional and modern characteristics.
      On the one hand, andrology keeps benefiting from the achievements of modern
      medicine and, on the other hand, it relies on the support of the theories of
      Traditional Chinese Medicine (TCM). An integration of Chinese and Western medical
      principles may further facilitate the development of andrology. TCM may
      contribute to the development of andrology by giving full play to its advantage
      as a psychosomatic medicine, enriching treatment strategies for male diseases
      with comprehensive TCM therapies, integrating the advantages of Western medicine
      to improve clinical efficacy, and normalizing the use of patent TCM drugs.

PMID- 29019222
TI  - [Differentiation of human umblical cord mesenchymal stem cells into Leydig cells
      in the rat testis interstitium: An experimental study].
AB  - Objective: To explore the feasibility of inducing human umbilical cord
      mesenchymal stem cells (HUMSCs) to differentiate into Leydig cells in the
      interstitial tissue of the rat testis. METHODS: HUMSCs were obtained by tissue
      blocks culture attachment and their purity and multi-lineage differentiation
      ability were verified by flow cytometry and chondrogenic/adipogenic/osteogenic
      differentiation. Then the HUMSCs were marked by CM-Dil and transplanted into the
      interstitial tissue of the rat testis. At 4 and 8 weeks after transplantation,
      the survival and differentiation status of the HUMSCs were observed by
      immunofluorescence staining and flow cytometry. The suspension of the rat Leydig
      cells was obtained at 8 weeks for determining the expression of the Leydig cell
      marker 3beta-HSD in the HUMSCs, the cells labeled with CM-Dil were sorted and
      cultured, and the medium collected after 3 days of culture for measurement of the
      testosterone level. RESULTS: The expression of the Leydig cell marker CYPllal was
      not observed in the HUMSCs at 4 weeks but found at 8 weeks after transplantation
      and the differentiation rate of 3beta-HSD was about 14.5% at 8 weeks. CM-Dil
      labeled cells survived after sorting and testosterone was detected in the medium.
      CONCLUSIONS: HUMSCs are likely to differentiate into Leydig cells in the
      interstitium of the rat testis.

PMID- 29019223
TI  - [Expression of pituitary tumor-transforming gene 1 during the development of
      androgen-independent prostate cancer].
AB  - Objective: To explore the expression of pituitary tumor transforming gene 1
      (PTTG1) during the transformation of prostate cancer from androgen-dependent
      (ADPC) to androgen-independent (AIPC). METHODS: We established an AIPC cell model
      LNCaP-AI by culturing the androgen-dependent LNCaP cell line in the hormone
      deprived medium for over 3 months. The cell model was verified and the PTTG1
      expression in the LNCaP cells was detected by Western blot and RT-PCR during
      hormone deprivation. RESULTS: The AIPC cell model LNCaP-AI was successfully
      established. The PTTG1 expression was gradually increased in the LNCaP cells with
      the prolonged time of hormone deprivation and the expressions of matrix
      metalloproteinases MMP-2 and -9 were elevated at the same time. CONCLUSIONS: The
      expression of PTTG1 is increased gradually in AIPC, which may be a target of gene
      therapy for advanced prostate cancer.

PMID- 29019224
TI  - [Diagnostic value of immunohistochemistry and FISH for chromosome 12p in type II
      testicular germ cell tumors].
AB  - Objective: To study the pathological morphology, immunohistochemical
      characteristics, and molecular changes of type II testicular germ cell tumors
      (TGCT) and investigate the possible value of immunohistochemistry and
      fluorescence in situ hybridization (FISH) in the diagnosis of TGCT. METHODS: We
      collected for this study 97 cases of TGCT, including 75 cases of seminoma, 17
      cases of embryonal carcinoma, 11 cases of yolk sac tumor, 16 cases of mature
      teratoma, 3 cases of immature teratoma, and 1 case of epidermoid cyst, in which
      normal testicular tissue was found in 20 and non-TGCT in 6. We detected the
      expressions of different antibodies in various subtypes of TGCT by
      immunohistochemistry and determined the rate of chromosome 12p abnormality using
      FISH. RESULTS: The immunophenotypes varied with different subtypes of TGCT. SALL4
      and PLAP exhibited high sensitivity in all histological subtypes. CD117 and OCT4
      showed strongly positive expressions in invasive seminoma and germ cell neoplasia
      in situ (GCNIS) but not in normal seminiferous tubules. GPC3 was significantly
      expressed in the yolk sac tumor, superior to GATA3 and AFP in both range and
      intensity. CKpan, OCT4, and CD30 were extensively expressed in embryonal
      carcinoma, while HCG expressed in choriocarcinoma. The positivity rate of
      isochromosome 12p and 12p amplification in TGCT was 96.7% (29/30). CONCLUSIONS:
      The majority of TGCT can be diagnosed by histological observation, but
      immunohistochemical staining is crucial for more accurate subtypes and valuable
      for selection of individualized treatment options and evaluation of prognosis.
      Chromosome 12p abnormality is a specific molecular alteration in type II TGCT,
      which is useful for ruling out other lesions.

PMID- 29019225
TI  - [Application value of real-time contrast-enhanced ultrasound in transrectal
      prostate biopsy].
AB  - Objective: To explore the application value of real-time contrast-enhanced
      ultrasound (RTCEU) in improving the detection rate of transrectal ultrasound
      guided prostate biopsy. METHODS: This prospective study included 91 male patients
      with abnormally high PSA (4-20 MUg/L) or abnormalities in DRE or MRI, who
      underwent 12+X prostate biopsy following conventional transrectal ultrasonography
      (TRUS) and RTCEU examination. We compared the numbers of suspected prostatic
      nodules before and after RTCEU as well as the detection rates of prostate cancer
      between conventional TRUS-guided 12PBx and 12PBx plus lesion-targeted biopsy
      procedures. RESULTS: Totally, 57 of the 86 suspected lesions on TRUS (66.3%), and
      108 of the 118 abnormal nodules on RTCEU (91.5%) were confirmed to be prostate
      cancer. RTCEU achieved a significantly higher detection rate than TRUS (P<0.01).
      A total of 39 cases of prostate cancer (42.8%) were detected by RTCEU, while only
      28 (30.7%) by TRUS, with statistically significant difference in the detection
      rate between the two procedures (P=0.033). CONCLUSIONS: Real-time contrast
      enhanced ultrasound can significantly improve the detection rate of prostate
      cancer and provide a valuable guide to targeted prostate biopsy.

PMID- 29019226
TI  - [Secondary male hypogonadism induced by sellar space-occupying lesion: Clinical
      analysis of 22 cases].
AB  - Objective: To analyze the clinical characteristics of secondary male hypogonadism
      induced by sellar space-occupying lesion, explore its pathogenesis, and improve
      its diagnosis and treatment. METHODS: We retrospectively analyzed the clinical
      data about 22 cases of secondary male hypogonadism induced by sellar space
      occupying lesion, reviewed related literature, and investigated the clinical
      manifestation, etiological factors, and treatment methods of the disease.
      Hypogonadism developed in 10 of the patients before surgery and radiotherapy
      (group A) and in the other 12 after it (group B). The patients received endocrine
      therapy with Andriol (n=7) or hCG (n=15). RESULTS: The average diameter of the
      sellar space-occupying lesions was significantly longer in group A than in B
      ([2.35+/-0.71] vs [1.83+/-0.36] cm, P<0.05) and the incidence rate of
      prolactinomas was markedly higher in the former than in the latter group (60% vs
      0, P<0.01). The levels of lutein hormone (LH), follicle stimulating hormone (FSH)
      and testosterone (T) were remarkably decreased in group B after surgery and
      radiotherapy (P<0.01). Compared with the parameters obtained before endocrine
      therapy, all the patients showed significant increases after intervention with
      Andriol or hCG in the T level ([0.78+/-0.40] vs [2.71+/-0.70] ng/ml with Andriol;
      [0.93+/-0.44] vs [3.07+/-0.67] ng/ml with hCG) and IIEF-5 score (5.00+/-2.61 vs
      14.50+/-3.62 with Andriol; 5.36+/-1.82 vs 15.07+/-3.27 with hCG) (all P<0.01).
      The testis volume increased and pubic hair began to grow in those with
      hypoevolutism. The patients treated with hCG showed a significantly increased
      testis volume (P<0.01) and sperm was detected in 7 of them, whose baseline testis
      volume was markedly larger than those that failed to produce sperm ([11.5+/-2.3]
      vs [7.5+/-2.3] ml, P<0.01). Those treated with Andriol exhibited no significant
      difference in the testis volume before and after intervention and produced no
      sperm, either. CONCLUSIONS: Hypothyroidism might be attributed to surgery- or
      radiotherapy-induced damage to the pituitary tissue, space-occupying effect of
      sellar lesion, and hyperprolactinemia. Both Andriol and hCG can improve the T
      level and erectile function, but the former does not help spermatogenesis.

PMID- 29019227
TI  - [Correlation of the inner diameter parameters of the spermatic vein in different
      positions and states of the varicocele patient with the results of seminal
      examination].
AB  - Objective: To study the correlation of the inner diameter parameters of the
      spermatic vein in different positions and states of the varicocele (VC) patient
      with the results of seminal examination. METHODS: A total of 149 VC patients
      underwent ultrasonography, routine semen examination, and sperm morphological
      analysis. The parameters obtained from ultrasonography included the bilateral
      testis volume in a supine position, the largest spermatic vein diameter in a
      supine position at rest (DSR), the largest spermatic vein diameter in a supine
      position following Valsalva manoeuvre (DSV), the largest spermatic vein diameter
      in an upright position at rest (DUR), and the largest spermatic vein diameter in
      an upright position following Valsalva manoeuvre (DUV). Then we calculated the
      parameters ?DS=DSV-DSR, ?DU=DUV-DUR, ?DR=DUR-DSR, and ?DV=DUV-DSV and analyzed
      the correlation of the above parameters with the results of semen examination
      using the ROC curve. RESULTS: Based on the results of semen examination, 119
      (79.87%) of the patients were allocated to the abnormal group and the other 30
      (20.13%) to the normal group. Statistically significant differences were observed
      between the two groups in ?DU (P=0.007), ?DR (P=0.0001), and ?DV (P=0.04), but
      not in DSR (P=0.35), DSV (P=0.34), DUR (P=0.06), DUV (P=0.12), and ?DS (P=0.64),
      nor in the volume of the testis affected (P=0.323). The area under the ROC curve
      was 0.55 for DSR, 0.57 for DSV, 0.64 for DUR, 0.62 for DUV, 0.49 for ?DS, 0.28
      for ?DU, 0.86 for ?DR, and 0.69 for ?DV. The corresponding cutoff values were
      2.25, 2.51, 2.48, 2.63, 0.30, 0.23, 0.25, and 0.20, the corresponding
      sensitivities of semen detection were 50.42%, 65.55%, 60.50%, 60.50%, 49.90%,
      29.41%, 79.83%, and 65.55%, and the corresponding specificities were 56.67%,
      63.33%, 63.33%, 63.33%, 56.67%, 33.33%, 80%, and 63.33%, respectively.
      CONCLUSIONS: The difference between the largest spermatic vein diameters in
      supine and upright positions at rest provides a high diagnostic accuracy for
      semen detection and helps to predict abnormality in seminal examination for VC
      patients.

PMID- 29019228
TI  - [Psycho-social factors of sexual failure among newly married Uyghur young males].
AB  - Objective: To study the psycho-social risk factors of sexual failure among newly
      married young males in the Uyghur population. METHODS: We conducted a paired case
      control study of 186 newly married Uyghur young males (aged 17-30 [23.4+/-2.9]
      yr) with sexual failure and another 186 (aged 18-34 [24.0+/-3.1] yr) with no such
      problem as controls. We performed a logistic regression analysis on the possible
      psycho-social risk factors of this condition. RESULTS: Logistic regression
      analysis showed that the risk factors of sexual failure among the newly married
      men included personality (OR=0.271, 95% CI 0.176-0.420), income (OR=0.391, 95% CI
      0.264-0.580), history of masturbation (OR=0.824, 95% CI 0.710-0.956), premarital
      sex (OR=0.757, 95% CI 0.677-0.847), sense of obligation (OR=1.756, 95% CI 1.157
      2.693), equality of the social status (OR=0.574, 95% CI 0.435-0.756), degree of
      mutual care (OR=1.605, 95% CI 1.268-2.032), female's psychological obstacle
      (OR=2.832, 95% CI 1.221-6.569), and religion (OR=0.643, 95% CI 0.472-0.967).
      There was a statistical significance in the correlation between these factors and
      sexual failure in the newly married males (all P<0.05). CONCLUSIONS: Sexual
      failure of newly married Uyghur young males are associated with many psycho
      social factors, which necessitates sexual education among young males and
      particularly pre-marriage sexual education and psychological guide among both
      males and females.

PMID- 29019229
TI  - [Transurethral resection of the prostate versus transurethral holmium laser
      enucleation of the prostate for benign prostatic hyperplasia with bladder
      detrusor overactivity].
AB  - Objective: To compare and analyze the effects of transurethral resection of the
      prostate (TURP) and transurethral holmium laser enucleation of the prostate
      (HoLEP) in the treatment of benign prostatic hyperplasia (BPH) with bladder
      detrusor overactivity. METHODS: his study included 51 cases of BPH with bladder
      detrusor overactivity treated by TURP and another 58 treated by HoLEP. We
      evaluated the urination of the two groups of patients during the recovery period
      and at 3 and 6 months postoperatively. RESULTS: There were no statistically
      significant differences in such baseline data as the blood PSA level, prostate
      volume, International Prostate Symptom Score (IPSS), and quality of life (QOL)
      between the two groups of patients, except in effective bladder capacity, which
      was higher in the TURP than in the HoLEP group ([315+/-59] vs [287+/-76] ml,
      P<0.05). Urine storage symptoms were obviously improved in both of the groups
      postoperatively, with the storage symptoms score significantly decreased from
      12.6+/-4.9 preoperatively to 7.5+/-3.9 at 3 months and 6.1+/-4.2 at 6 months
      after surgery in the TURP group (P<0.01) and from 13.7+/-5.7 to 7.9+/-4.2 and
      7.0+/-5.1 in the HoLEP group (P<0.01). HoLEP manifested significant advantages
      over TURP in the postoperative urethral catheterization time ([2.7+/-0.8] vs
      [5.1+/-1.2] d, P<0.05), postoperative bladder contracture time ([4.1+/-1.9] vs
      [5.8+/-2.4] d, P<0.05), postoperative hospital stay ([4.4+/-1.8] vs [5.9+/-2.5]
      d, P<0.05), and improvement of the maximum urinary flow rate, which was increased
      from (7.9+/-3.7) ml/s preoperatively to (16.8+/-4.3) ml/s at 3 months after
      surgery in the HoLEP group and from (8.6+/-3.2) ml/s to (14.6+/-4.3) ml/s in the
      TURP group (P<0.05). CONCLUSIONS: Both TURP and HoLEP can improve bladder
      function and detrusor overactivity in BPH patients, with similar effects in
      improving urination at 3 to 6 months after surgery. However, HoLEP has more
      advantages over TURP during the period of postoperative recovery.

PMID- 29019231
TI  - [Application of microdissection testicular sperm extraction in non-obstructive
      azoospermia].
AB  - The development of testicular sperm extraction (TESE) and intracytoplasmic sperm
      injection (ICSI) has made it possible for patients with non-obstructive
      azoospermia to have their own children. However, sperm retrieval by conventional
      TESE succeeds but in a subset of patients and, therefore, how to improve the
      success rate of sperm retrieval is becoming a focus of research. Recent studies
      suggest that microdissection TESE, although with its limitations, has obvious
      advantages over traditional sperm retrieval methods. This article presents an
      overview on the characteristics, predictive factors, sperm retrieval rate, post
      operative complications, and improvement of microdissection TESE.

PMID- 29019230
TI  - [Effect of salidroside on the expression of connexin43 in the corpus cavernosum
      smooth muscle cells of hypoxic rats].
AB  - Objective: To investigate the effect of salidroside on the expression of the
      connexin43 (Cx43) protein in the corpus cavernosum smooth muscle cells (CCSMCs)
      of hypoxic SD rats. METHODS: CCSMCs were cultured in vitro and identified by
      immunofluorescence staining. The cells were divided into six groups: normal
      control (21% O2), hypoxia (1% O2), hypoxia+salidroside (HS) 8 MUg/ml,HS 16
      MUg/ml, HS 32 MUg/ml, and HS 64 MUg/ml, and cultured for 48 hours. Then the
      relative expression of Cx43 in different groups was detected by Western blot.
      RESULTS: The in vitro cultured CCSMCs grew well and 90% of the cells showed
      positivity for alpha-SMA and desmin on immunohistochemistry. Salidroside <=64
      MUg/ml produced no obvious toxicity on the CCSMCs. The expressions of Cx43 and
      phosphorylated proteins were dramatically increased in the hypoxia group as
      compared with the normal control (P<0.01 and P<0.05). The HS groups all showed
      significantly higher expression of Cx43 than the hypoxia group (P<0.01), but the
      phosphorylation rate of the Cx43 proteins was remarkably decreased (P<0.01).
      CONCLUSIONS: Hypoxia increases the expression of Cx43 in the CCSMCs of SD rats.
      Salidroside <=64 MUg/ml cannot reverse the hypoxia-induced change but can reduce
      the dephosphorylation of Cx43 in CCSMCs. It is deduced that salidroside can
      protect CCSMCs by decreasing the phosphorylation of Cx43 and suppressing hypoxia
      induced formation of the gap junction channel.

PMID- 29019232
TI  - [Prostatic urethral lift: A novel minimally invasive treatment for benign
      prostatic hyperplasia].
AB  - Benign prostatic hyperplasia (BPH) and BPH-induced lower urinary tract symptoms
      (LUTS) are common factors influencing the quality of life (QOL) of elderly males.
      In case of undesirable or adverse effects of medication, many BPH patients seek
      surgical treatment. Transurethral resection of the prostate (TURP), though
      evidently effective for BPH, fails to preserve the sexual function and therefore
      reduces the QOL of the patients. Moreover, some elderly patients with
      comorbidities may be unfit for TURP. Prostatic urethral lift (PUL) is a newly
      developed surgical procedure for the treatment of LUTS secondary to BPH. With the
      advantages of minimal invasiveness, low rate of peri- and post-operative
      complications, and maximal preservation of patients' erectile and ejaculatory
      functions, PUL is winning more and more attention from the clinicians and
      patients.

PMID- 29019233
TI  - PEGylated Red-Emitting Calcium Probe with Improved Sensing Properties for
      Neuroscience.
AB  - Monitoring calcium concentration in the cytosol is of main importance as this ion
      drives many biological cascades within the cell. To this end, molecular calcium
      probes are widely used. Most of them, especially the red emitting probes, suffer
      from nonspecific interactions with inner membranes due to the hydrophobic nature
      of their fluorophore. To circumvent this issue, calcium probes conjugated to
      dextran can be used to enhance the hydrophilicity and reduce the nonspecific
      interaction and compartmentalization. However, dextran conjugates also feature
      important drawbacks including lower affinity, lower dynamic range, and slow
      diffusion. Herein, we combined the advantage of molecular probes and dextran
      conjugate without their drawbacks by designing a new red emitting turn-on calcium
      probe based on PET quenching, Rhod-PEG, in which the rhodamine fluorophore bears
      four PEG4 units. This modification led to a high affinity calcium probe (Kd = 748
      nM) with reduced nonspecific interactions, enhanced photostability, two-photon
      absorbance, and brightness compared to the commercially available Rhod-2. After
      spectral characterizations, we showed that Rhod-PEG quickly and efficiently
      diffused through the dendrites of pyramidal neurons with an enhanced sensitivity
      (DeltaF/F0) at shorter time after patching compared to Rhod-2.

PMID- 29019234
TI  - A Sensitive Electrochemical Aptasensor for Thrombin Detection Based on
      Electroactive Co-Based Metal-Organic Frameworks with Target-Triggering NESA
      Strategy.
AB  - In this work, an improved target-triggering nicking enzyme signaling
      amplification (NESA) strategy as signal enhancer has been fabricated to obtain a
      sensitive electrochemical thrombin (TB) biosensor combined with PtPd NPs
      decorated electroactive Co-based metal-organic frameworks (Co-MOFs/PtPdNPs) as a
      redox mediator. Traditionally, in the NESA strategy, only one of the output
      double strands DNA is available in the next cycle. However, in this work, all of
      the output DNA involved in the improved NESA strategies could be further
      employed, resulting in high utilization of output DNA, which further enhanced
      signal amplification and sensitivity of the biosensor. In addition, the
      electroactive Co-MOFs were not only used as nanocarriers but also acted as signal
      labels, avoiding adding extra redox media. Simultaneously, in the presence of
      H2O2, PtPd NPs decorated on the Co-MOFs act the same as horseradish peroxidase to
      promote the oxidation of H2O2, further promoting the conversion of Co2+ to Co3+,
      leading to electrochemical signal amplification. With such design, the TB
      biosensor exhibited good sensitivity from 1 pM to 30 nM with a detection limit of
      0.32 pM. This new NESA strategy with high utilization of output DNA can supply
      one efficient approach to improve signal amplification, which also open an avenue
      for sensitivity enhancement in detection of analytes.

PMID- 29019236
TI  - Fluctuation Scaling, Calibration of Dispersion, and Detection of Differences.
AB  - Fluctuation scaling describes the relationship between the mean and standard
      deviation of a set of measurements. An example is Horwitz scaling, which has been
      reported from interlaboratory studies. Horwitz and similar studies have reported
      simple exponential and segmented scaling laws with exponents (alpha) typically
      between 0.85 (Horwitz) and 1 when not operating near a detection limit. When
      approaching a detection limit, the exponents change and approach an apparently
      Gaussian (alpha = 0) model. This behavior is often presented as a property of
      interlaboratory studies, which makes controlled replication to understand the
      behavior costly to perform. To assess the contribution of instrumentation to
      larger scale fluctuation scaling, we measured the behavior of two inductively
      coupled plasma atomic emission spectrometry (ICP-AES) systems, in two
      laboratories measuring thulium using two emission lines. The standard deviation
      universally increased with the uncalibrated signal, indicating the system was
      heteroscedastic. The response from all lines and both instruments was consistent
      with a single exponential dispersion model having parameters alpha = 1.09 and
      beta = 0.0035. No evidence of Horwitz scaling was found, and there was no
      evidence of Poisson noise limiting behavior. The "Gaussian" component was a
      consequence of background subtraction for all lines and both instruments. The
      observation of a simple exponential dispersion model in the data allows for the
      definition of a difference detection limit (DDL) with universal applicability to
      systems following known dispersion. The DDL is the minimum separation between two
      points along a dispersion model required to claim they are different according to
      a particular statistical test. The DDL scales transparently with the mean and
      works at any location in a response function.

PMID- 29019235
TI  - The Impact of Protonation on Early Translocation of Anthrax Lethal Factor:
      Kinetics from Molecular Dynamics Simulations and Milestoning Theory.
AB  - We report atomically detailed molecular dynamics simulations of the permeation of
      the lethal factor (LF) N-terminal segment through the anthrax channel. The N
      terminal chain is unstructured and leads the permeation process for the LF
      protein. The simulations were conducted in explicit solvent with milestoning
      theory, making it possible to extract kinetic information from nanosecond to
      millisecond time scales. We illustrate that the initial event is strongly
      influenced by the protonation states of the permeating amino acids. While the N
      terminal segment passes easily at high protonation state through the anthrax
      channel (and the phi clamp), the initial permeation represents a critical step,
      which can be irreversible and establishes a hook in the channel mouth.

PMID- 29019237
TI  - Sugar-Assisted Photogeneration of Didehydrotoluenes from Chlorobenzylphosphonic
      Acids.
AB  - Irradiation of the three isomeric chlorobenzylphophonic acids in aqueous buffer
      led to a pH-dependent photochemistry. Under acidic conditions (pH = 2.5),
      photocleavage of the Ar-Cl bond occurred and a phenyl cation chemistry resulted.
      Under basic conditions (pH = 11), a photoinduced release of the chloride anion
      followed by the detachment of the metaphosphate anion gave alpha,n
      didehydrotoluene diradicals (alpha,n-DHTs), potential DNA cleaving intermediates.
      At a physiological pH (pH = 7.2), both a cationic and a diradical reactivity took
      place depending on the phosphonic acid used. It is noteworthy that the
      complexation exerted by a monosaccharide (glucose or methylglucopyranoside)
      present in solution induced an exclusive formation of alpha,n-DHTs. The
      mechanistic scenario of the different photoreactivities occurring when changing
      the pH of the solution and the role of the various intermediates (phenyl cations,
      diradicals, etc.) in the process was studied by computational analysis.

PMID- 29019238
TI  - Total Synthesis and Anti-inflammatory Evaluation of Penchinone A and Its
      Structural Analogues.
AB  - The first total synthesis and biological evaluation of penchinone A and its
      structural analogues are described. The key steps for the preparation of
      penchinone A derivatives involve the oxime-directed palladium(II)-catalyzed
      oxidative acylation, Claisen rearrangement, and base-mediated olefin migration.
      This transformation efficiently provides a range of allyl-substituted biaryl
      ketones with site-selectivity and functional group compatibility. In addition,
      all synthetic compounds were screened for anti-inflammatory activity against
      nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL
      6) with lipopolysaccharide (LPS)-induced RAW264.7 cells. Generally, a range of
      penchinone A derivatives potently inhibited NO, TNF-alpha, and IL-6 productions,
      compared to dexamethasone as a positive control. Notably, penchinone A (8g) and
      its derivatives (8e and 8f) were found to exhibit anti-inflammatory activity
      stronger than that of dexamethasone.

PMID- 29019239
TI  - Enhanced DC-Operated Electroluminescence of Forwardly Aligned   p/MQW/n InGaN
      Nanorod LEDs via DC Offset-AC Dielectrophoresis.
AB  - We introduce an orientation-controlled alignment process of p-GaN/InGaN
      multiquantum-well/n-GaN (p/MQW/n InGaN) nanorod light-emitting diodes (LEDs) by
      applying the direct current (DC) offset-alternating current (AC) or pulsed DC
      electric fields across interdigitated metal electrodes. The as-forwardly aligned
      p/MQW/n InGaN nanorod LEDs by a pulsed DC dielectrophoresis (DEP) assembly
      process improve the electroluminescence (EL) intensities by 1.8 times compared to
      the conventional AC DEP assembly process under DC electric field operation and
      exhibit an enhanced applied current and EL brightness in the current-voltage and
      EL intensity-voltage curves, which can be directly used as the fundamental data
      to construct DC-operated nanorod LED devices, such as LED areal surface
      lightings, scalable lightings (micrometers to inches) and formable surface
      lightings. The enhancement in the applied current, the improved EL intensity, and
      the increased number of forwardly aligned p/MQW/n InGaN nanorods in panchromatic
      cathodoluminescence images confirm the considerable enhancement of forwardly
      aligned one-dimensional nanorod LEDs between two opposite electrodes using DC
      offset-AC or a pulsed DC electric field DEP assembly process. These DC offset-AC
      or pulsed DC electric field DEP assembly processes suggest that designing for
      these types of interactions could yield new ways to control the orientation of
      asymmetric p/MQW/n InGaN diode-type LED nanorods with a relatively low aspect
      ratio.

PMID- 29019241
TI  - Fine-Tuning of Photophysical and Electroluminescence Properties of
      Benzothiadiazole-Based Emitters by Methyl Substitution.
AB  - New benzothiadiazole-based materials containing methyl substitution are prepared
      and characterized as promising green/yellowish green emitters for
      electroluminescent applications. The dyes exhibited shorter wavelength absorption
      and emission when compared to nonmethylated dyes. A dye containing methyl group
      on the donor side exhibited blue shift in absorption and emission when compared
      to the analogous dye containing methyl group away from donor. The steric effect
      exerted by the methyl group is responsible for the nonplanar arrangement of donor
      and acceptor, which inhibited the intramolecular charge transfer. All the dyes
      displayed solvatochromism in the emission spectra characteristic of hybridization
      of local and charge transfer excited states. Due to the benefit of methyl group,
      the dyes restrained the formation of aggregates in the solid state. Solution
      processed multilayered OLED device were fabricated employing these compounds
      either as host emitters or dopant emitters in suitable host matrix and exhibited
      green/yellowish green electroluminescence with external quantum efficiency as
      high as 4.6% (15.7 cd A-1).

PMID- 29019240
TI  - pH-Dependent Assembly of Porphyrin-Silica Nanocomposites and Their Application in
      Targeted Photodynamic Therapy.
AB  - Structurally controlled nanoparticles, such as core-shell nanocomposite particles
      by combining two or more compositions, possess enhanced or new functionalities
      that benefited from the synergistic coupling of the two components. Here we
      report new nanocomposite particles with self-assembled porphyrin arrays as the
      core surrounded by amorphous silica as the shell. The synthesis of such
      nanocomposite nanoparticles was conducted through a combined surfactant micelle
      confined self-assembly and silicate sol-gel process using optically active
      porphyrin as a functional building block. Depending on kinetic conditions, these
      particles exhibit structure and function at multiple length scales and locations.
      At the molecular scale, the porphyrins as the building blocks provide well
      defined macromolecular structures for noncovalent self-assembly and unique
      chemistry for high-yield generation of singlet oxygen for photodynamic therapy
      (PDT). On the nanoscale, controlled noncovalent interactions of the porphyrin
      building block result in an extensive self-assembled porphyrin network that
      enables efficient energy transfer and impressive fluorescence for cell labeling,
      evidenced by absorption and photoluminescence spectra. Finally, the thin silicate
      shell on the nanoparticle surface allows easy functionalization, and the
      resultant targeting porphyrin-silica nanocomposites can selectively destroy tumor
      cells upon receiving light irradiation.

PMID- 29019242
TI  - Salivary Cystatins: Exploring New Post-Translational Modifications and
      Polymorphisms by Top-Down High-Resolution Mass Spectrometry.
AB  - Cystatins are a complex family of cysteine peptidase inhibitors. In the present
      study, various proteoforms of cystatin A, cystatin B, cystatin S, cystatin SN,
      and cystatin SA were detected in the acid-soluble fraction of human saliva and
      characterized by a top-down HPLC-ESI-MS approach. Proteoforms of cystatin D were
      also detected and characterized by an integrated top-down and bottom-up strategy.
      The proteoforms derive from coding sequence polymorphisms and post-translational
      modifications, in particular, phosphorylation, N-terminal processing, and
      oxidation. This study increases the current knowledge of salivary cystatin
      proteoforms and provides the basis to evaluate possible qualitative/quantitative
      variations of these proteoforms in different pathological states and reveal new
      potential salivary biomarkers of disease. Data are available via ProteomeXchange
      with identifier PXD007170.

PMID- 29019243
TI  - Label-Free Photoelectrochemical "Off-On" Platform Coupled with G-Wire-Enhanced
      Strategy for Highly Sensitive MicroRNA Sensing in Cancer Cells.
AB  - MicroRNA (miRNAs) quantification, especially at low abundance, is vital for
      disease diagnosis, prognosis, and therapy. Herein we develop a distinctive label
      free "off-on" configuration for photoelectrochemical (PEC) sensing platform
      fabrication, coupled with DNA four-way junction (4J) architecture as well as G
      wire superstructure for signal amplification. In addition, ultrathin copper
      phosphate nanosheets (CuPi NSs) coating Au nanoparticles (Au-CuPi NSs) serve as a
      highly efficient photocathode substrate. To improve the sensitivity, and avoid
      the false positive signals, the quencher, gold nanoparticles (GNPs), is utilized
      to switch off the PEC signal because of the commendable surface plasmon resonance
      (SPR) absorption. Subsequently, ingenious DNA 4J architecture is applied to
      export proportional c-myc regions for target quantification. Assisted with the G
      wire superstructure formation, the enhancer 5,10,15,20-tetra(4-sulfophenyl)
      21H,23H-porphyrin (TSPP) is coupled on the substrate to switch on the PEC signal,
      thus realizing the miRNA assay with persuasive accuracy, high sensitivity, and
      low detection limit. In addition, we execute the miRNA detection in prostate
      carcinoma cell line 22Rv1, and acquire desirable quantitative capability.
      Remarkably, the prepared PEC sensing platform not only realizes the highly
      efficient miRNAs quantification, but also uncovers a marvelous horizon for
      sensing platform fabrication.

PMID- 29019244
TI  - Interindividual Variability in Metabolism of [6]-Shogaol by Gut Microbiota.
AB  - [6]-Shogaol (6S), one of the major bioactive components in dry ginger, is
      attracting considerable attention because of its wide spectrum of biological
      activities, but its metabolic fate is still not fully understood. In the present
      study, the microbial metabolism of 6S was examined for the first time in in vitro
      batch fecal fermentation system and in mice. Two major microbial metabolites were
      detected and identified as 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol (M9) and 1
      (4'-hydroxy-3'-methoxyphenyl)-decan-3-one (M11). Our results indicated that
      reductions of the double bond and the ketone group are the major metabolic
      pathways of 6S by the human gut microbiota. We also observed the interindividual
      variability in the metabolism of M11 to M9 by human gut microbiota. In addition,
      we demonstrated that the glucuronidated form of 6S and its metabolites could be
      rapidly deconjugated by human gut microbiota and in mice, which can be regarded
      as a reactive process taking place in the intestinal tract. To our knowledge,
      this is the first report involving the identification of the microbial
      metabolites of 6S in an in vitro fermentation system, and the first demonstration
      of the critical role of gut microbiota in producing the bioactive free form of 6S
      and its metabolites in the intestinal tract in mice.

PMID- 29019246
TI  - Wearable Ring-Based Sensing Platform for Detecting Chemical Threats.
AB  - This work describes a wireless wearable ring-based multiplexed chemical sensor
      platform for rapid electrochemical monitoring of explosive and nerve-agent
      threats in vapor and liquid phases. The ring-based sensor system consists of two
      parts: a set of printed electrochemical sensors and a miniaturized electronic
      interface, based on a battery-powered stamp-size potentiostat, for signal
      processing and wireless transmission of data. A wide range of electrochemical
      capabilities have thus been fully integrated into a 3D printed compact ring
      structure, toward performing fast square-wave voltammetry and chronoamperometric
      analyses, along with interchangeable screen-printed sensing electrodes for the
      rapid detection of different chemical threats. High analytical performance is
      demonstrated despite the remarkable miniaturization and integration of the ring
      system. The attractive capabilities of the wearable sensor ring system have been
      demonstrated for sensitive and rapid voltammetric and amperometric monitoring of
      nitroaromatic and peroxide explosives, respectively, along with amperometric
      biosensing of organophosphate (OP) nerve agents. Such ability of the miniaturized
      wearable sensor ring platform to simultaneously detect multiple chemical threats
      in both liquid and vapor phases and alert the wearer of such hazards offers
      considerable promise for meeting the demands of diverse defense and security
      scenarios.

PMID- 29019245
TI  - Decalin-Containing Tetramic Acids and 4-Hydroxy-2-pyridones with Antimicrobial
      and Cytotoxic Activity from the Fungus Coniochaeta cephalothecoides Collected in
      Tibetan Plateau (Medog).
AB  - New tetramic acid derivatives, (+/-)-conipyridoins A-D (1-4), conipyridoins E (5)
      and F (6), and new 4-hydroxy-2-pyridone alkaloids (+/-)-didymellamide E (7), (+)
      didymellamide B (8), (+)-N-hydroxyapiosporamide (9), and didymellamides F-H (10
      12) were isolated and identified from the solid culture of the fungus Coniochaeta
      cephalothecoides. Chiral resolution of 1, 2, 3, 4, and 7 gave five pairs of
      enantiomers: 1a/1b, 2a/2b, 3a/3b, 4a/4b, and 7a/7b, respectively. Stereochemistry
      of 1a and 1b, and 2a and 2b was established and confirmed by the single-crystal X
      ray diffraction and electronic circular dichroism (ECD) methods. Absolute
      configuration in 3a, 3b, 4a, 4b, 7a, and 7b was assigned by ECD calculations.
      Compounds 1-6 possess an unprecedented chemical skeleton featuring a decalin ring
      and a tetramic acid moiety. Compound 11 significantly inhibited the growth of
      Candida albicans and Aspergillus fumigatus with minimum inhibitory concentration
      (MIC) of 3.13 and 1.56 MUM, respectively, and was further confirmed to be a new
      chitin synthesis inhibitor. Compound 5 exhibited the strongest activity against
      the growth of both Staphylococcus aureus and MRSA with MIC value of 0.97 MUM. In
      the light of a co-occurrence of 3-acyl tetramic acids and biogenetically related
      pyridine alkaloids, the biosynthetic pathway for 1-12 was postulated.

PMID- 29019247
TI  - Export of Plastic Debris by Rivers into the Sea.
AB  - A substantial fraction of marine plastic debris originates from land-based
      sources and rivers potentially act as a major transport pathway for all sizes of
      plastic debris. We analyzed a global compilation of data on plastic debris in the
      water column across a wide range of river sizes. Plastic debris loads, both
      microplastic (particles <5 mm) and macroplastic (particles >5 mm) are positively
      related to the mismanaged plastic waste (MMPW) generated in the river catchments.
      This relationship is nonlinear where large rivers with  population-rich
      catchments delivering a disproportionately higher fraction of MMPW into the sea.
      The 10 top-ranked rivers transport 88-95% of the global load into the sea. Using
      MMPW as a predictor we calculate the global plastic debris inputs form rivers
      into the sea to range between 0.41 and 4 * 106 t/y. Due to the limited amount of
      data high uncertainties were expected and ultimately confirmed. The empirical
      analysis to quantify plastic loads in rivers can be extended easily by additional
      potential predictors other than MMPW, for example, hydrological conditions.

PMID- 29019248
TI  - Amorphous Phosphorus-Incorporated Cobalt Molybdenum Sulfide on Carbon Cloth: An
      Efficient and Stable Electrocatalyst for Enhanced Overall Water Splitting over
      Entire pH Values.
AB  - The development of economical, proficient, and highly stable catalysts to
      substitute the expensive noble metal electrodes for electrocatalytic water
      splitting applications is exceedingly desirable. In this context, the most
      fascinating and challenging approach is the rational design of a nanocomposite
      encompassing multiple components with unique functionalities. Herein, we describe
      the fabrication of a strongly catalytic and superb durable phosphorus
      incorporated cobalt molybdenum sulfide electrocatalyst grown on carbon cloth (P
      CoMoS/CC). The hybrid material exhibited excellent activity for hydrogen and
      oxygen evolution reactions over a wide range of pH (1-14) with extremely high
      stability (~90% retention of the initial current density) after 24 h of
      electrolysis. Importantly, when P-CoMoS/CC was used as both cathode and anode for
      overall water splitting, a very low cell voltage of 1.54 V is required to attain
      the 10 mA cm-2 current density, and the hybrid material exhibited a long-term
      stability (89.8% activity retention after 100 h). The outstanding overall water
      splitting performance compared to an electrolyzer consisting of the noble-metal
      based catalysts Pt/C and RuO2 makes P-CoMoS one of the most efficient earth
      abundant water-splitting catalysts. Phosphorus incorporation was proved to be a
      vital aspect for the improved charge-transfer properties and catalytic durability
      of the P-CoMoS/CC catalyst.

PMID- 29019249
TI  - Electrochemical ATR-SEIRAS Using Low-Cost, Micromachined Si Wafers.
AB  - Thin, micromachined Si wafers, designed as internal reflection elements (IREs)
      for attenuated total reflectance infrared spectroscopy, are adapted to serve as
      substrates for electrochemical ATR surface enhanced infrared absorption
      spectroscopy (ATR-SEIRAS). The 500 MUm thick wafer IREs with groove angles of 35
      degrees  are significantly more transparent at long mid-IR wavelengths as
      compared to conventional large Si hemisphere IREs. The appeal of greater
      transparency is mitigated by smaller optical throughput at larger grazing angles
      and steeper angles of incidence at the reflecting plane that reduce the
      enhancement factor. Through use of the potential dependent adsorption of 4
      methoxypyridine (MOP) as a test system, the microgroove IRE is shown to provide
      relatively strong electrochemical ATR-SEIRAS responses when the angle of incident
      radiation is between 50 and 55 degrees , corresponding to refracted angles
      through the crystal of ~40 degrees . The higher than expected enhancement is
      attributed to attenuation of the reflection loss of p-polarized light and
      multiple reflections within the wafer-based IRE. The micromachined IREs are shown
      to outperform a 25 mm radius hemisphere in terms of S/N at wavenumbers less than
      ca. 1400 cm-1 despite the weaker signal enhancement derived from the steeper
      angle incident on the IRE/sample interface. The high optical transparency of the
      new IREs allows the spectral observation of displaced water libration bands at
      ca. 730 cm-1 upon solvent replacement by adsorbed MOP. The results are highly
      encouraging for the further development of low-cost, Si wafer-based IREs for
      electrochemical ATR-SEIRAS applications.

PMID- 29019250
TI  - A bull horn fragment found on colonoscopy.
AB  - An 81-year-old man with mild iron deficiency anemia (Hb 12 g/dl) and a positive
      fecal occult blood test was referred for a colonoscopy. The patient was
      asymptomatic and not undergoing any treatment. A foreign body that crossed the
      colonic lumen and prevented the colonoscope progression was identified at 40 cm
      from the anal verge via colonoscopy. The object seemed to be hard and fixed when
      manipulated with biopsy forceps.

PMID- 29019251
TI  - Complete tubular colonic duplication in an adult: a rare incidental finding and
      the risk of colonoscopic perforation.
AB  - Gastrointestinal duplications are unusual congenital malformations, nearly always
      diagnosed in childhood. Roughly 80% are cysts-like lesions and only a small
      percentage (4-18%) involves the colonic wall. Almost all are asymptomatic and
      therefore diagnosed as an incidental finding on imaging tests or when become
      complicated and present with perforation or bleeding. The need for an elective
      surgical treatment is controversial and should be indicated on an individual
      basis. This report is a case of an adult with a complete tubular colonic
      duplication found incidentally by colonoscopy that required surgical treatment
      due to perforation.

PMID- 29019252
TI  - Hypersplenism secondary to splenoportal axis compression by a giant hepatic cyst.
AB  - Simple hepatic cysts (SHCs) are formations that contain serous fluid surrounded
      by normal hepatic parenchyma with no communication with intrahepatic bile ducts.
      Symptoms develop as a result of their size or complications such as bleeding,
      rupture, intracystic infection or compression of adjacent structures.

PMID- 29019253
TI  - Immune mediated colitis caused by lung cancer treatment with atezolizumab.
AB  - Atezolizumab is an IgG1 isotype monoclonal antibody against the protein
      programmed cell death-ligand 1 (PD- L1). PD-L1 may be highly expressed in some
      tumors and is believed to inhibit immune cells that recognize and attack tumor
      cells. Inhibition of PD-L1 can remove its inhibitory effect and provoke an anti
      tumor response. In October 2016, the Food and Drugs Administration (FDA) approved
      atezolizumab for the treatment of patients with metastatic non-small cell lung
      cancer after disease progression during or following platinum based chemotherapy.
      We present the case of a 43-year-old male with stage IV lung adenocarcinoma in
      progression, despite standard chemotherapy.

PMID- 29019256
TI  - Can Hospitals Contribute to the Public's Health?

PMID- 29019255
TI  - Expression profiles and associations of muscle regulatory factor (MRF) genes with
      growth traits in Tibetan chickens.
AB  - 1. Muscle regulatory factors (MRFs), including Myf5, Myf6 (MRF4/herculin), MyoD
      and MyoG (myogenin), play pivotal roles in muscle growth and development.
      Therefore, they are considered as candidate genes for meat production traits in
      livestock and poultry. 2. The objective of this study was to investigate the
      expression profiles of these genes in skeletal muscles (breast muscle and thigh
      muscle) at 5 developmental stages (0, 81, 119, 154 and 210 d old) of Tibetan
      chickens. Relationships between expressions of these genes and growth and carcass
      traits in these chickens were also estimated. 3. The expression profiles showed
      that in the breast muscle of both genders the mRNA levels of MRF genes were
      highest on the day of hatching, then declined significantly from d 0 to d 81, and
      fluctuated in a certain range from d 81 to d 210. However, the expression of
      Myf5, Myf6 and MyoG reached peaks in the thigh muscle in 118-d-old females and
      for MyoD in 154-d-old females, whereas the mRNA amounts of MRF genes in the male
      thigh muscle were in a narrow range from d 0 to d 210. 4. Correlation analysis
      suggested that gender had an influence on the relationships of MRF gene
      expression with growth traits. The RNA levels of MyoD, Myf5 genes in male breast
      muscle were positively related with several growth traits of Tibetan chickens (P
      < 0.05). No correlation was found between expressions of MRF genes and carcass
      traits of the chickens. 5. These results will provide a base for functional
      studies of MRF genes on growth and development of Tibetan chickens, as well as
      selective breeding and resource exploration.

PMID- 29019254
TI  - Psychometric evaluation of HIV risk behavior assessments using Audio Computer
      Assisted Self-Interviewing (ACASI) among orphans and vulnerable children in
      Zambia.
AB  - Social desirability bias and underreporting of HIV risk behaviors are significant
      challenges to the accurate evaluation of HIV prevention programs for orphans and
      vulnerable children (OVC) in sub-Saharan Africa. Valid and reliable HIV risk
      behavior instruments are critical to address these challenges. We assessed the
      psychometric properties of two risk behavior measures, the World Aids Foundation
      Survey (WAF) and the Peer HIV Risk Behavior Screener (PHRBS), administered to 210
      OVC in Zambia using Audio Computer Assisted Self-Interviewing. All WAF subscales
      exhibited good internal reliability (alpha > .80); only the Sexual Behavior
      Practices subscale strongly distinguished (P < .01) adolescents who engaged in
      HIV risk behaviors ("cases") from those who did not ("non-cases"). An 8-item
      version of the PHRBS, refined using exploratory factor analysis, demonstrated
      good internal reliability (alpha = 87), differentiated "cases" from "non-cases"
      (P < .01), and correlated strongly with the Sexual Behavior Practices subcale (r
      = .34, P < .01). Results suggest that report of peers' sexual behaviors can serve
      as a proxy for OVCs' own behavior in contexts where social desirability bias
      affects reporting.

PMID- 29019259
TI  - Encourage students and trainees to get started in medical education.

PMID- 29019257
TI  - Catastrophic Health Expenditure Among Colorectal Cancer Patients and Families: A
      Case of Malaysia.
AB  - This study aimed to estimate the cost of colorectal cancer (CRC) management and
      to explore the prevalence and determinants of catastrophic health expenditure
      (CHE) among CRC patients and their families arising from the costs of CRC
      management. Data were collected prospectively from 138 CRC patients. Patients
      were interviewed by using a structured questionnaire at the time of the
      diagnosis, then at 6 months and 12 months following diagnosis. Simple descriptive
      methods and multivariate binary logistic regression were used in the analysis.
      The mean cost of managing CRC was RM8306.9 (US$2595.9), and 47.8% of patients'
      families experienced CHE. The main determinants of CHE were the economic status
      of the family and the likelihood of the patient undergoing surgery. The results
      of this study strongly suggest that stakeholders and policy makers should provide
      individuals with financial protection against the consequences of cancer, a
      costly illness that often requires prolonged treatment.

PMID- 29019260
TI  - Teaching exchange.

PMID- 29019261
TI  - Innovations and developments.

PMID- 29019262
TI  - The mentoring needs of trainees in family practice.

PMID- 29019265
TI  - Sinking skin flap syndrome following decompressive craniectomy.

PMID- 29019266
TI  - Liposome-loaded thermo-sensitive hydrogel for stabilization of SN-38 via
      intratumoral injection: optimization, characterization, and antitumor activity.
AB  - Main challenges of the clinical use of 7-ethyl-10-hydroxycamptothecin (SN-38) are
      its facile transition between the active lactone form (SN-38 A) and the inactive
      carboxylate form (SN-38I) under physiological conditions and its low solubility.
      The purpose of this study was to develop a thermo-sensitive hydrogel system with
      acidic SN-38 liposomes (SN-38-Lip-Gel) for local chemotherapy to solve these
      problems and to evaluate its antitumor activity and tissue distribution in tumor
      bearing mice. A study of structural conversion between SN-38I and SN-38 A under
      various pH conditions indicated that acidic solution could inhibit the
      conversion. Namely, a preparation with low pH was essential to stabilize lactone
      form of SN-38. SN-38-Lip-Gel had an appropriate gelation time (GT) at 25/37 
      degrees C. The particle size of SN-38-Lip-Gel was similar to that of SN-38-Lip.
      SN-38-Lip-Gel showed a slower release than SN-38-Lip in vitro. SN-38-Lip-Gel
      suggested pH-dependent stability, the percentage of SN-38 A remaining decreased
      along with the increasing pH. In vivo studies SN-38-Lip-Gel showed better
      antitumor efficacy and lower systemic toxicity compared with other groups at the
      same drug dose. In conclusion, SN-38-Lip-Gel could improve the effective use of
      SN-38 by stabilizing the lactone form, extending the drug release, providing a
      high local drug concentration, and reducing systemic toxicity.

PMID- 29019268
TI  - Editorial.

PMID- 29019270
TI  - Electronic memory aids for people with dementia experiencing prospective memory
      loss: A review of empirical studies.
AB  - This paper details a review of the literature on the use of electronic aids for
      prospective memory for people with dementia. Key findings of the review are that:
      electronic memory aids show potential for supporting people's prospective memory
      but the devices and software applications need further development in order to
      function reliably; sample sizes of studies are often very small, limiting the
      generalisability of their findings; few studies of devices are conducted in
      users' home environments; and most of the studies focus on the effectiveness of
      the electronic memory aid, rather than outcomes for users, such as improved daily
      functioning, quality of life, or social connectedness. The review concludes that
      future studies with robust devices are required that explicitly focus on the
      varying needs and capacities of people with dementia, in order to generate
      additional evidence for the effectiveness of electronic memory aids for this
      cohort.

PMID- 29019267
TI  - GE11 peptide conjugated selenium nanoparticles for EGFR targeted oridonin
      delivery to achieve enhanced anticancer efficacy by inhibiting EGFR-mediated
      PI3K/AKT and Ras/Raf/MEK/ERK pathways.
AB  - Selenium nanoparticles (Se NPs) have attracted increasing interest in recent
      decades because of their anticancer, immunoregulation, and drug carrier
      functions. In this study, GE11 peptide-conjugated Se NPs (GE11-Se NPs), a
      nanosystem targeting EGFR over-expressed cancer cells, were synthesized for
      oridonin delivery to achieve enhanced anticancer efficacy. Oridonin loaded and
      GE11 peptide conjugated Se NPs (GE11-Ori-Se NPs) were found to show enhanced
      cellular uptake in cancer cells, which resulted in enhanced cancer inhibition
      against cancer cells and reduced toxicity against normal cells. After
      accumulation into the lysosomes of cancer cells and increase of oridonin release
      under acid condition, GE11-Ori-Se NPs were further transported into cytoplasm
      after the damage of lysosomal membrane integrity. GE11-Ori-Se NPs were found to
      induce cancer cell apoptosis by inducting reactive oxygen species (ROS)
      production, activating mitochondria-dependent pathway, inhibiting EGFR-mediated
      PI3K/AKT and inhibiting Ras/Raf/MEK/ERK pathways. GE11-Se NPs were also found to
      show active targeting effects against the tumor tissue in esophageal cancer
      bearing mice. And in nude mice xenograft model, GE11-Ori-Se NPs significantly
      inhibited the tumor growth via inhibition of tumor angiogenesis by reducing the
      angiogenesis-marker CD31 and activation of the immune system by enhancing IL-2
      and TNF-alpha production. The selenium contents in mice were found to accumulate
      into liver, tumor, and kidney, but showed no significant toxicity against liver
      and kidney. This cancer-targeted design of Se NPs provides a new strategy for
      synergistic treating of cancer with higher efficacy and reduced side effects,
      introducing GE11-Ori-Se NPs as a candidate for further evaluation as a
      chemotherapeutic agent for EGFR over-expressed esophageal cancers.

PMID- 29019269
TI  - The burden of severe hypoglycemia in type 1 diabetes.
AB  - AIMS: Approximately 1.25 million people in the US have type 1 diabetes mellitus
      (T1DM), a chronic metabolic disease that develops from the body's inability to
      produce insulin, and requires life-long insulin therapy. Poor insulin adherence
      may cause severe hypoglycemia (SHO), leading to hospitalization and long-term
      complications; these, in turn, drive up costs of SHO and T1DM overall. This
      study's objective was to estimate the prevalence and costs of SHO-related
      hospitalizations and their additional longer-term impacts on patients with T1DM
      using basal-bolus insulin. METHODS: Using Truven MarketScan claims, we identified
      adult T1DM patients using basal-bolus insulin regimens who were hospitalized for
      SHO (inpatient SHO patients) during 2010-2015. Two comparison groups were
      defined: those with outpatient SHO-related encounters only, including emergency
      department (ED) visits without hospitalization (outpatient SHO patients), and
      those with no SHO- or acute hyperglycemia-related events (comparison patients).
      Lengths of stay and SHO-related hospitalization costs were estimated and
      propensity score and inverse probability weighting methods were used to adjust
      for baseline differences across the groups to evaluate longer-term impacts.
      RESULTS: We identified 8,734 patients, of which 4.2% experienced at least one SHO
      related hospitalization. Among those who experienced SHO (i.e. of those in the
      inpatient and outpatient SHO groups), 31% experienced at least one SHO-related
      hospitalization, while 9% were treated in the ED without subsequent
      hospitalization. Approximately 79% of patients were admitted directly to the
      hospital; the remainder were first assessed or treated in the ED. The inpatient
      SHO patients stayed in the hospital, including time in the ED, for 1.7 days and
      incurred $3551 in costs. About one-third of patients were hospitalized again for
      SHO. Inpatient SHO patients incurred significantly higher monthly costs after
      their initial SHO-related hospitalization than patients in the two other groups
      ($2084 vs $1313 and $1372), corresponding to 59% or 52% higher monthly costs for
      inpatient SHO patients. LIMITATIONS: These analyses excluded patients who did not
      seek ED or hospital care when faced with SHO; events may have been miscoded; and
      we were not able to account for clinical characteristics associated with SHO,
      such as insulin dose and duration of diabetes, or unmeasured confounders.
      CONCLUSIONS: The burden associated with SHO is not negligible. About 4% of T1DM
      patients using basal-bolus insulin regimens are hospitalized at least once due to
      SHO. Not only did those patients incur the costs of their SHO hospitalization,
      but they also incur red at least $712 (52%) more in costs per month after their
      hospitalization than outpatient SHO or comparison patients. Reducing SHO events
      can help decrease the burden associated with SHO among patients with T1DM.

PMID- 29019271
TI  - Development of a Tandem Repeat-Based Polymerase Chain Displacement Reaction
      Method for Highly Sensitive Detection of 'Candidatus Liberibacter asiaticus'.
AB  - Huanglongbing (HLB) is one of the most destructive diseases in citrus production
      worldwide. Early detection of HLB pathogens can facilitate timely removal of
      infected citrus trees in the field. However, low titer and uneven distribution of
      HLB pathogens in host plants make reliable detection challenging. Therefore, the
      development of effective detection methods with high sensitivity is imperative.
      This study reports the development of a novel method, tandem repeat-based
      polymerase chain displacement reaction (TR-PCDR), for the detection of
      'Candidatus Liberibacter asiaticus', a widely distributed HLB-associated
      bacterium. A uniquely designed primer set (TR2-PCDR-F/TR2-PCDR-1R) and a
      thermostable Taq DNA polymerase mutant with strand displacement activity were
      used for TR-PCDR amplification. Performed in a regular thermal cycler, TR-PCDR
      could produce more than two amplicons after each amplification cycle. Sensitivity
      of the developed TR-PCDR was 10 copies of target DNA fragment. The sensitive
      level was proven to be 100* higher than conventional PCR and similar to real-time
      PCR. Data from the detection of 'Ca. L. asiaticus' with filed samples using the
      above three methods also showed similar results. No false-positive TR-PCDR
      amplification was observed from healthy citrus samples and water controls. These
      results thereby illustrated that the developed TR-PCDR method can be applied to
      the reliable, highly sensitive, and cost-effective detection of 'Ca. L.
      asiaticus'.

PMID- 29019272
TI  - Amitriptyline and Sexual Function: A Systematic Review Updated for Sexual Health
      Practice.
AB  - Amitriptyline is an old drug but is still prevalently used as the first-line
      treatment for a variety of common diseases. Surprisingly, knowledge of sexual
      risks with amitriptyline comes from only one clinical trial and several case
      reports from three decades ago. In the current study, a systematic review of the
      literature following the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses (PRISMA) related to amitriptyline and sexual dysfunction (SD) was
      performed. The frequency, gender-difference, types, disease-specificity and time
      course of SD, and the relationship between SD and nonsexual adversity were
      studied. A total of 14 publications, including 8 qualified randomized clinical
      trials, were eligible. The frequency of SD in overall, male and female patients
      was 5.7, 11.9 and 1.7%, respectively. SD was six-fold higher in men than women.
      The frequency of SD was 6.9% in depressive patients compared with 0.8% in non
      depressive patients ( p = .008), and gradually decreased at 8 weeks after
      treatment ( p = .02). Amitriptyline impacted arousal and libido more than orgasm
      and ejaculation in male patients but mainly libido in female patients. SD was
      significantly correlated with insomnia linearly whereas somnolence and nausea
      dually. Therefore, amitriptyline-associated SD mainly occurs in depressive and
      male patients, disturbs each phase of the sexual response cycle in men but mainly
      libido in women, gradually decreases under long-term treatment, and can be
      predicted by the co-existence of insomnia, somnolence or nausea during treatment.
      Clinicians should caution and tailor the gender and disease vulnerability of
      amitriptyline in their practice.

PMID- 29019273
TI  - Dentists' use of digital radiographic techniques: Part I - intraoral X-ray: a
      questionnaire study of Swedish dentists.
AB  - OBJECTIVE: The present study aims to gain knowledge about the dentist's use and
      choice of digital intraoral imaging methods. MATERIALS AND METHODS: A
      questionnaire sent to 2481 dentists within the Swedish Dental Society contained
      questions about the type of X-ray technique used, problems experienced with
      digital radiography, and reasons for choosing digital technology, and about
      indications, clinic size and type of service. Response rate was 53%. RESULTS:
      Ninety-eight percent of the dentists had made the transition to digital
      radiography; only 2% used film technique, and solid-state detector (SSD) was the
      most used digital technique. More years in service decreases the likelihood of
      applying individual indications for performing a full mouth examination. More
      retakes were done with SSDs compared to storage phosphor plates. Reasons for
      choosing digital techniques were that work was easier and communication with the
      patients improved. However, dentists also experienced problems with digital
      techniques, such as exposure and projection errors and inadequate image quality.
      The Swedish Radiation Safety Authority states that all radiological examinations
      should be justified, something not always followed. CONCLUSIONS: This study
      showed that 98% of the respondents, Swedish dentists within the Swedish Dental
      Society, used digital techniques, and the most used was the solid-state
      technique.

PMID- 29019275
TI  - Identification of DNA methylation and transcriptional regulatory regions in the
      promoter of duck retinoic acid inducible gene I (RIG-I).
AB  - 1. The aim of this study was to identify the active control area of the duck
      retinoic acid-inducible gene I (duRIG-I) core promoter, to predict the binding
      sites of transcription factors and to provide a theoretical basis for the study
      of duRIG-I function and mechanism of regulation. 2. The promoter region of duRIG
      I was obtained from Ensembl; the CpG island in the duRIG-I promoter was predicted
      online; and the methylation status of the duRIG-I promoter was detected by the
      bisulphite sequencing PCR method. 3. There was an obvious CpG island in the duRIG
      I promoter, with a total of 44 CG dinucleotides. However, the level of
      methylation was hypomethylation (0.2%). 4. The core transcriptional regulatory
      region was identified, localised between -301 and ~+14 bp, where multiple
      transcription factor binding sites including IRF1, RXRbeta, AP-2alphaA, RAP1, NF
      1 and SP1 motifs were identified that significantly enhanced RIG-I promoter
      activity.

PMID- 29019274
TI  - Effects of whole-body vibration on balance and mobility in institutionalized
      older adults: a randomized controlled trial.
AB  - OBJECTIVE: To investigate whether a comprehensive exercise program was effective
      in improving physical function among institutionalized older adults and whether
      adding whole-body vibration to the program conferred additional therapeutic
      benefits. DESIGN: A single-blinded randomized controlled trial was conducted.
      SETTING: This study was carried out in residential care units. PARTICIPANTS: In
      total, 73 older adults (40 women, mean age: 82.3 +/- 7.3 years) were enrolled
      into this study. INTERVENTIONS: Participants were randomly allocated to one of
      the three groups: strength and balance program combined with whole-body
      vibration, strength and balance program without whole-body vibration, and social
      and recreational activities consisting of upper limb exercises only. All
      participants completed three training sessions per week for eight weeks. OUTCOME
      MEASURES: Assessment of mobility, balance, lower limb strength, walking
      endurance, and self-perceived balance confidence were conducted at baseline and
      immediately after the eight-week intervention. Incidences of falls requiring
      medical attention were recorded for one year after the end of the training
      period. RESULTS: A significant time * group interaction was found for lower limb
      strength (five-times-sit-to-stand test; P = 0.048), with the exercise-only group
      showing improvement (pretest: 35.8 +/- 16.1 seconds; posttest: 29.0 +/- 9.8
      seconds), compared with a decline in strength among controls (pretest: 27.1 +/-
      10.4 seconds; posttest: 28.7 +/- 12.3 seconds; P = 0.030). The exercise with
      whole-body vibration group had a significantly better outcome in balance
      confidence (pretest: 39.2 +/- 29.0; posttest: 48.4 +/- 30.6) than the exercise
      only group (pretest: 35.9 +/- 24.8; posttest: 38.2 +/- 26.5; P = 0.033).
      CONCLUSION: The exercise program was effective in improving lower limb strength
      among institutionalized older adults but adding whole-body vibration did not
      enhance its effect. Whole-body vibration may improve balance confidence without
      enhancing actual balance performance.

PMID- 29019276
TI  - Benzo(a)pyrene induces lung toxicity and inflammation in mice: prevention by
      carvacrol.
AB  - Benzo(a)pyrene (B(a)P) is an environmental pollutant which causes various lung
      toxicities. The present study was designed to evaluate the protective effects of
      carvacrol, a monoterpenic phenol against B(a)P-induced lung toxicity. In this
      study, Swiss albino mice were pretreated with carvacrol (25 mg/kg and 50 mg/kg)
      orally for 7 consecutive days before administering oral B(a)P (125 mg/kg).
      Preventive efficacy of carvacrol was assessed in terms of membrane oxidation,
      antioxidant enzyme activities, histopathological changes, and inflammatory (iNOS,
      NF-kappaB, and COX-2) markers. Carvacrol pretreatment in the two doses restored
      B(a)P-induced lipid peroxidation and increased the activities of antioxidant
      enzymes. Protein expressions of iNOS, NF-kappaB, and COX-2 in the lung tissue
      were found to be upregulated by B(a)P. Carvacrol treatment, however,
      downregulated their expressions by decreasing the marker of positive stained
      cells and restored the histopathological architecture of lung tissue. Our results
      suggest that carvacrol can be used as a protective agent against B(a)P-induced
      lung toxicity and inflammation.

PMID- 29019277
TI  - 3D CBCT morphometric assessment of mental foramen in Arabic population and global
      comparison: imperative for invasive and non-invasive procedures in mandible.
AB  - BACKGROUND: Recent advancements in clinical dentistry have increased the
      possibilities of surgical procedures in the mental region. A detailed knowledge
      of mental foramen (MF) morphometry is significant to preserve integrity of the
      mental nerve trunk in surgical interventions such as orthognathic surgery,
      implant placement and anaesthetic block. OBJECTIVE: The aim of this study was to
      determine the most accurate position of the mental foramen by using new
      assessment approach in a sample of dental patients presenting to the specialist
      dental clinic, College of Dentistry, Al Jouf University, Saudi Arabia. STUDY
      DESIGN: A retrospective study was performed using cone beam computed tomography
      (CBCT) of 600 patients (40.1 +/- 11.78 years old). Following inclusion and
      exclusion criteria, 395 CBCT were finally obtained and analyzed for the most
      accurate position of the mental foramen (MF) by OnDemand 3D software (Seoul,
      Korea). Prevalence of shape of MF and accessory MF were also assessed. Pearson
      chi-square test was employed to test significant differences between genders and
      races. RESULTS: The most common horizontal and vertical position of the mental
      foramen was in line with the long axis of 2nd premolar (41.3%) and below the root
      apex level (93.2%), respectively. The most common shape of MF was round type
      (72.66%). The prevalence of accessory 2MF and 3MF was 2.28% and 0.25%,
      respectively. CONCLUSION: New information about MF presented in this article can
      help anatomists, prosthodontists, orthodontists, surgeons, forensic odontologists
      and paleoanthropologists to predict the position of the MF and perform safer
      surgeries.

PMID- 29019278
TI  - Recent developments with rhodanine as a scaffold for drug discovery.
AB  - INTRODUCTION: Rhodanines, as one of the 4-thiazolidinones subtypes, are
      recognized as privileged heterocycles in medicinal chemistry. The main
      achievements include the development of drug-like molecules with numerous
      biological activities as well as approved drugs. Among rhodanines, 5-ene
      rhodanines are of special interest, and are often claimed as pan assay
      interference compounds due to Michael acceptor functionality. Areas covered:
      Herein, the synthetic protocols for rhodanines and their transformation are
      reviewed. Biological activity is briefly discussed as well as biotargets, mode of
      actions and optimization directions. Furthermore, the utilization of 5-ene
      rhodanines in Michael additions are discussed while both pro and contra arguments
      have been outlined within medicinal chemistry application. Expert opinion:
      Rhodanines remain privileged heterocycles in drug discovery. They are accessible
      building blocks for optimization and transformation into related heterocycles,
      simplified analogues and fused heterocycles with a thiazolidine framework.
      Michael acceptor functionality, as well as the thesis about low selectivity
      towards biotargets of rhodanines, must be confirmed experimentally and it cannot
      be based on just the presence of conjugated alpha,beta-unsaturated carbonyl.
      Moreover, the positive aspects of Michael acceptors must be considered as well as
      their multitarget properties. New criteria for target affinity must be found. In
      conclusion, rhodanines are generally not problematic per se.

PMID- 29019279
TI  - Leucine and resistance training improve hyperglycemia, white adipose tissue loss,
      and inflammatory parameters in an experimental model of type 1 diabetes.
AB  - BACKGROUND: Loss of white adipose tissue (WAT), associated with type 1 diabetes
      (DM1), contributes to increased chronic systemic inflammation. AIM: The aim of
      this study was to investigate the effects of leucine supplementation and
      resistance training (RT) in attenuating WAT loss and improving inflammatory
      parameters and glucose metabolism in DM1 rats. METHODS: Thirty-two male Wistar
      rats were distributed into four groups: DA (sedentary and supplemented with non
      essential amino acids (NEAA)), DL (sedentary and supplemented with leucine), DTA
      (submitted to RT and supplemented with NEAA) and DTL (submitted to RT and
      supplemented with leucine). DM1 was induced by streptozotocin (STZ). An 8-week
      period of RT consisted of climbing a ladder with a progressively increased load,
      and supplementation was offered in the feed. RESULTS: Glycemia, polyphagia and
      polydipsia were lower in DL, DTA and DTL groups compared with the DA group by
      approximately 20% ( p<.0001), 28% ( p=.004) and 64% ( p<.0001), respectively.
      Weight of total WAT and retroperitoneal adipose tissue (RPAT) were higher by
      approximately 21% ( p=.01) and 54% ( p=.0004), respectively, in DL, DTA and DTL
      groups compared with DA. However, gene expression of adiponectin and leptin in
      RPAT was only increased by RT (DTA and DTL) compared with DA and DL by
      approximately 93% ( p<.0001) and 78% ( p=.0002), respectively. Similarly, the
      levels of adiponectin in the serum, tissue IL-10 (RPAT) and serum IL-10 were only
      increased in DTA and DTL compared with DA and DL by approximately 31% ( p=.03),
      45% ( p=.0009) and 35% ( p=.003), respectively. CONCLUSIONS: Both interventions,
      isolated or together, reduced hyperglycemia and excessive loss of WAT, but RT was
      the main factor responsible for attenuating inflammation.

PMID- 29019280
TI  - Social inequality and barriers to cardiac rehabilitation in the rehab-North
      register.
AB  - AIM: Barriers to participation in cardiac rehabilitation (CR) may occur at three
      levels of the referral process (lack of information, declining to participate,
      and referral to appropriate CR programme). The aim is to analyse the impact of
      socioeconomic status on barriers to CR and investigate whether such barriers
      influenced the choice of referral. METHODS: The Rehab-North Register, a cross
      sectional study, enrolled 5455 patients hospitalised at Aalborg University
      Hospital with myocardial infarction (MI) during 2011-2014. Patients hospitalised
      with ST-elevated MI and complicated non-ST-elevated MI were to be sent to
      specialized CR, whereas patients with uncomplicated non-ST-elevated MI and
      unstable angina pectoris were to be sent to community-based CR. Detailed selected
      socioeconomic information was gathered from statistical registries in Statistics
      Denmark. Data was assessed using logistic regression. RESULTS: Patients being
      retired, low educated, and/or with an annual gross income <27.000 Euro/yr were
      significantly less informed about cardiac rehabilitation programmes. Patients
      being older than 70 years, retired, low educated and/or with an annual gross
      income <27.000 Euro were significantly less willing to participate in CR.
      Further, this patient population were to a higher extent referred to community
      based CR. CONCLUSION: Patients with low socioeconomic status received less
      information about and were less willing to participate in cardiac rehabilitation.
      The same patient population was to a higher extent referred to community-based
      CR. Knowledge about barriers at different levels and the impact of social
      inequality may help in tailoring a better approach in the referral process to CR.

PMID- 29019281
TI  - The Chronic Care Model to Improve Management of Childhood Obesity.
AB  - One-third of children in the United States are overweight or obese. Comorbidities
      continue into adulthood if a healthy weight is not established. While expert
      guidelines for management of this condition are recognized, provider adherence to
      guidelines is lacking. The purpose of this quality improvement project was to
      evaluate the effectiveness of the chronic care model (CCM) on improving primary
      care provider identification, prevention, and management of childhood overweight
      and obesity. A pre- and postintervention chart audit was completed to evaluate
      documentation of 20 assessment measures included in expert guidelines. A chi
      square analysis was conducted to assess differences. Statistically significant
      improvements were found in documentation of parental obesity, family medical
      history, sleep assessment, endocrine assessment, and weight classification as a
      diagnosis. Use of the CCM had a positive impact on provider adherence to expert
      guidelines. Furthermore, not all aspects of the CCM must be used to see
      statistically significant improvements.

PMID- 29019282
TI  - Negotiating Gender Norms to Support Men in Psychological Distress.
AB  - Underpinning a general pattern of higher suicide rates in men is the assumption
      that men do not ask for help or utilize the health-care system during times of
      psychological distress. There has been a failure to grapple with the dynamic of
      when, how and from whom men might ask for help during times of psychological
      distress, and what key barriers or enabling factors are likely to influence
      potential help-givers' capacity or willingness to offer help to men in
      psychological distress. The aim of this study was to investigate how masculine
      norms impact men's help-seeking as well as care givers' behaviors and willingness
      to support men in need of psychological help or perceived to be at risk of
      suicide. Focus groups ( n = 13) were used with "high-risk suicide" groups of men
      and community gatekeepers. The principles of grounded theory were used for data
      analysis. Three themes emerged: "negotiating ways to ask for, offer and accept
      help without compromising masculinity"; "making and sustaining contact with men
      in psychological distress"; and "navigating roles responsibilities and boundaries
      to support men in psychological distress." Approaches to suicide prevention need
      to take account of how masculine norms shape men's willingness to ask for and
      accept help during times of psychological distress as well as care givers
      willingness to offer help. The findings address a gap in the literature by
      looking beyond men's help-seeking as a passive, one dimensional construct, to a
      more dynamic triad of help-seeking/giving/taking behaviors that are embedded in
      the sociocultural context of men's lives.

PMID- 29019283
TI  - Antitumor effectiveness and mechanism of action of Ru(II)/amino acid/diphosphine
      complexes in the peritoneal carcinomatosis progression.
AB  - Peritoneal carcinomatosis is considered as a potentially lethal clinical
      condition, and the therapeutic options are limited. The antitumor effectiveness
      of the [Ru(l-Met)(bipy)(dppb)]PF6(1) and the [Ru(l-Trp)(bipy)(dppb)]PF6(2)
      complexes were evaluated in the peritoneal carcinomatosis model, Ehrlich ascites
      carcinoma-bearing Swiss mice. This is the first study that evaluated the effect
      of Ru(II)/amino acid complexes for antitumor activity in vivo. Complexes 1 and 2
      (2 and 6 mg kg-1) showed tumor growth inhibition ranging from moderate to high.
      The mean survival time of animal groups treated with complexes 1 and 2 was higher
      than in the negative and vehicle control groups. The induction of Ehrlich ascites
      carcinoma in mice led to alterations in hematological and biochemical parameters,
      and not the treatment with complexes 1 and 2. The treatment of Ehrlich ascites
      carcinoma-bearing mice with complexes 1 and 2 increased the number of Annexin V
      positive cells and cleaved caspase-3 levels and induced changes in the cell
      morphology and in the cell cycle phases by induction of sub-G1 and G0/G1 cell
      cycle arrest. In addition, these complexes reduce angiogenesis induced by Ehrlich
      ascites carcinoma cells in chick embryo chorioallantoic membrane model. The
      treatment with the LAT1 inhibitor decreased the sensitivity of the Ehrlich
      ascites carcinoma cells to complexes 1 and 2 in vitro-which suggests that the
      LAT1 could be related to the mechanism of action of amino acid/ruthenium(II)
      complexes, consequently decreasing the glucose uptake. Therefore, these complexes
      could be used to reduce tumor growth and increase mean survival time with less
      toxicity than cisplatin. Besides, these complexes induce apoptosis by combination
      of different mechanism of action.

PMID- 29019284
TI  - MiR-503 enhances the radiosensitivity of laryngeal carcinoma cells via the
      inhibition of WEE1.
AB  - Enhancing the sensitivity of laryngeal cells to radiation is crucial for
      improving the efficacy of laryngeal carcinoma. MicroRNAs are known to play a
      major role in regulating cellular radiosensitivity. This study was designed to
      explore the effect and the molecular basis of miR-503 in the radiosensitivity of
      laryngeal carcinoma cells. Quantitative real-time polymerase chain reaction
      analysis showed that miR-503 expression was decreased in human laryngeal
      carcinoma cell lines Hep-2 and TU212, and the downregulation of miR-503 was also
      observed after irradiation. Upregulation of miR-503 by pre-miR-503 transfection
      restrained proliferation, promoted progression of Hep-2 and TU212 cells through
      the cell cycle after irradiation, and sensitized cells to radiation. Dual
      Luciferase Reporter Assay verified a direct interaction between miR-503 and the
      WEE1 messenger RNA 3'-untranslated region. The overexpression of miR-503
      significantly decreased WEE1 expression at the messenger RNA and protein levels,
      whereas the inhibition of miR-503 upregulated the expression of WEE1. WEE1
      knockdown by WEE1 small interfering RNA apparently abrogated the inhibitory
      effect of anti-miR-503 on radiosensitivity. In conclusion, miR-503 could function
      as an enhancer of radiation responses in laryngeal carcinoma cells by inhibiting
      WEE1, which may be a potential novel radiosensitizing strategy for laryngeal
      carcinoma.

PMID- 29019286
TI  - The neglected vulva.

PMID- 29019285
TI  - PDGFRalpha promoter polymorphisms and expression patterns influence risk of
      development of imatinib-induced thrombocytopenia in chronic myeloid leukemia: A
      study from India.
AB  - Platelet-derived growth factor receptor has been implicated in many malignant and
      non-malignant diseases. Platelet-derived growth factor receptor-alpha is a
      tyrosine kinase and a side target for imatinib, a revolutionary drug for the
      treatment of chronic myeloid leukemia that has dramatically improved the survival
      of chronic myeloid leukemia patients. Given the importance of platelet-derived
      growth factor receptor in platelet development and its inhibition by imatinib, it
      was intriguing to analyze the role of platelet-derived growth factor receptor
      alpha in relation to imatinib treatment in the development of imatinib-induced
      thrombocytopenia in chronic myeloid leukemia patients. We hypothesized that two
      known functional polymorphisms, +68GA insertion/deletion and -909C/A, in the
      promoter region of the platelet-derived growth factor receptor-alpha gene may
      affect the susceptibility of chronic myeloid leukemia patients receiving imatinib
      treatment to the development of thrombocytopenia. A case-control study was
      conducted among a cohort of chronic myeloid leukemia patients admitted to the Lok
      Nayak Hospital, New Delhi, India. A set of 100 patients of chronic myeloid
      leukemia in chronic phase and 100 age- and sex-matched healthy controls were
      studied. After initiation of imatinib treatment, the hematological response of
      chronic myeloid leukemia patients was monitored regularly for 2 years, in which
      the development of thrombocytopenia was the primary end point. Platelet-derived
      growth factor receptor-alpha promoter polymorphisms +68GA ins/del and -909C/A
      were studied by allele-specific polymerase chain reaction. Platelet-derived
      growth factor receptor-alpha messenger RNA expression was evaluated by
      quantitative real-time polymerase chain reaction. The messenger RNA expression
      results were expressed as 2-Deltact +/- standard deviation. The distribution of
      +68GA ins/del promoter polymorphism genotypes differed significantly between the
      thrombocytopenic and non-thrombocytopenic chronic myeloid leukemia patient groups
      (p < 0.0001). Moreover, +68GA del/del and ins/del genotypes in imatinib-treated
      chronic myeloid leukemia patients were associated with an increased risk of
      developing thrombocytopenia, with odds ratios 6.5 (95% confidence interval = 2.02
      0.89, p = 0.001) and 6.0 (95% confidence interval = 2.26-15.91, p = 0.0002),
      respectively. Similarly, -909C/A promoter polymorphism genotype distribution also
      differed significantly between thrombocytopenic and non-thrombocytopenic chronic
      myeloid leukemia patient groups (p = 0.02), and a significantly increased risk of
      imatinib-induced thrombocytopenia was associated with -909C/A polymorphism mutant
      homozygous (AA) genotypes the odds ratio being 7.7 (95% confidence interval 1.50
      to 39.91, p = 0.009). However, no significant risk of imatinib-induced
      thrombocytopenia was found to be associated with heterozygous genotype (-909C/A)
      with odds ratio 1.9 (95% confidence interval = 0.86-4.56, p = 1.14). Platelet
      derived growth factor receptor-alpha messenger RNA expression was significantly
      higher in chronic myeloid leukemia patients compared to controls (p = 0.008).
      Moreover, patients with imatinib-induced thrombocytopenia had a significantly
      lower platelet-derived growth factor receptor-alpha messenger RNA expression,
      compared to patients without thrombocytopenia (p = 0.01). A differential
      expression of platelet-derived growth factor receptor-alpha messenger RNA was
      observed with respect to different +68 GA ins/del and -909C/A polymorphism
      genotypes. The +68GA deletion allele and -909A allele were significantly
      associated with lower expression of platelet-derived growth factor receptor-alpha
      messenger RNA. The platelet-derived growth factor receptor-alpha +68GA del/del,
      +68GA ins/del, and -909AA genotypes are associated with an increased risk of
      developing thrombocytopenia in imatinib-treated chronic myeloid leukemia
      patients. A significantly lower platelet-derived growth factor receptor-alpha
      messenger RNA expression accompanies the +68GA deletion allele in an allele dose
      dependent manner. Platelet-derived growth factor receptor-alpha -909AA genotype
      is also associated with lower expression of platelet-derived growth factor
      receptor-alpha. The downregulation of platelet-derived growth factor receptor
      alpha expression may play a causative role in imatinib-induced thrombocytopenia,
      a common side effect, in the subset of chronic myeloid leukemia patients with
      platelet-derived growth factor receptor-alpha +68 GA ins/del, +68 GA del/del, and
      -909C/A genotypes.

PMID- 29019287
TI  - Racial/Ethnic Differences in Parent-Child Smoking Communication.
AB  - A cross-sectional study of parents and children who presented to the ED at a
      Cincinnati hospital showed high parental smoking rates and lower rates of anti
      smoking communication in African American parents, unlike prior studies.

PMID- 29019288
TI  - Native People and the DSM IV-TR.
AB  - Native people, as everyone else, are impacted in diverse ways by various social
      stressors that can trigger dysfunctional behavior, such as substance abuse.
      Although, the DSM IV-TR acknowledges cultural differences and their effect upon
      dysfunction, it does not deal with pressures from the outside world that often
      impact diverse cultures in parallel ways. Here, three such diagnostic criteria
      (Bereavement, Identity Problem, and Acculturation Problem), that are presented in
      an abbreviated fashion within the DSM IV-TR, are given a more robust treatment in
      order to facilitate dysfunctional behavior among Native people, such as substance
      abuse.

PMID- 29019289
TI  - Race/Ethnic Differences in Alcohol Abuse Among Youth.
AB  - OBJECTIVE: Black and Hispanic youth are less likely to abuse alcohol than White
      youth. However, the reasons for these race/ ethnic differences in alcohol abuse
      are unclear. The present study explores whether the variations can be explained,
      in part, by racial/ethnic differences in attitudes toward risk. METHOD: The
      National Household Survey of Drug Abuse, 2001 (n = 32,798) is used to explore
      race/ethnic differences in risk-taking attitudes and whether these attitudes
      serve to mediate race/ethnic differences in heavy drinking and drinking and
      driving. RESULTS: Bivariate analyses reveal that Black and Hispanic youth have
      lower rates of alcohol abuse and a lower propensity for risk-taking than White
      youth. Logistic regressions reveal that the differences in risk-taking explain
      (but do not completely account for) observed differences in alcohol abuse. These
      findings are present for both males and females. Results more generally reveal
      that social and economic ad vantages are associated with risk-taking attitudes
      and thus indirectly contribute to alcohol abuse. CONCLUSIONS: Researchers have
      long been surprised that minority youth exhibit lower rates of alcohol abuse than
      White youth since socioeconomic disadvantage often contributes to substance
      abuse. However, the present study suggests that social and economic disadvantages
      might also suppress risk-taking propensities, which in turn may reduce the
      incidence of alcohol abuse. Additional research is needed to understand the
      mechanisms by which social and cultural resources affect attitudes toward risk.

PMID- 29019290
TI  - Exploring the Temporal Relationship Between Race and the Use of Ecstasy.
AB  - Previous research has suggested that the use of 3, 4
      methylenedioxymethamphetamine (MDMA or "ecstasy") is primarily concentrated among
      white users. These studies, however, have all been conducted at single points in
      time. No research has examined the temporal relationship between race and the use
      of ecstasy. In the current study, we use data collected from respondents surveyed
      through the National Household Survey on Drug Abuse between 1990 and 2001. Chi
      square statistics are used to explore the temporal relationship between race and
      the use of ecstasy during this time frame. While lifetime prevalence estimates
      are low relative to other populations, a consistent, statistically significant
      relationship between race and ecstasy use is discerned throughout the 1990s.
      Policy implications are assessed in light of the findings.

PMID- 29019291
TI  - Illegal Drug Use in Orthodox Jewish Adolescents.
AB  - Orthodox Jewish adolescents are increasingly seeking stimulation with illegal
      drugs. Eleven Orthodox Jewish adolescents were surveyed with semi-structured
      interviews on the Orthodox Jewish cultural aspects of their illegal drug use.
      Adolescents had mixed beliefs about religious teachings affecting their illegal
      drug use. No consistent pattern existed for particular ethnic aspects of Orthodox
      Jewish religious practice as a risk factor for illegal drug use. Language used to
      describe illegal drug use in this population is described. Unlike illegal drug
      use in secular and non-Jewish adolescents, these adolescents reported very little
      family discord or poor relationships with their parents.

PMID- 29019292
TI  - Racial/Ethnic Differences in Dually Diagnosed Anglo and Ethnic Minority Women
      Receiving Chemical Dependency Treatment.
AB  - This article examines racial/ethnic differences in a sample of 51 dually
      diagnosed women who received chemical dependency treatment. Comparisons are made
      between Anglo and racial/ethnic minority women at admission to the inpatient
      treatment program and at follow-up where data are available. Findings from a
      repeated measures design showed significant decreases in several problem domains
      for the overall sample. Significant racial/ethnic differences were found only for
      the other drugs domain. Anglo women reported greater decreases than racial/ethnic
      minority women in the majority of the domains. Findings suggest continued
      investigations to inform culturally competent treatment for all dually diagnosed
      women.

PMID- 29019293
TI  - Evolution of the concept of oxygen transport in the critically ill, with a focus
      on children after cardiopulmonary bypass.
AB  - The concept of oxygen transport, defined as the relation between oxygen
      consumption (VO2) and delivery (DO2), is of fundamental importance in critically
      ill patients. The past 200 years have witnessed a stepwise progressive
      improvement in the understanding of pathophysiological disturbances in the
      balance of DO2 and VO2 in critically ill patients including those after
      cardiopulmonary bypass surgery. Intermittent spectacular technological
      achievements have accelerated the rate of progress. Therapeutic advances have
      been particularly impressive during the recent decades. Examination of the
      relation between DO2 and VO2 provides a useful framework around which the care of
      the critically ill may be developed. Until now, only a few groups have used this
      framework to examine children after cardiopulmonary bypass. The key topics that
      will be covered in this review article are the evolution of the concept from its
      early development to its present, increasingly sophisticated, role in the
      management of critically ill patients, with a focus on children after
      cardiopulmonary bypass surgery.

PMID- 29019294
TI  - Participation sociale et personnes ayant des atteintes cognitives et centre
      communautaire de loisir : une equation possible?
AB  - Validating support of social participation for people with cognitive impairment
      (CI) plays a predominant role in maintaining identity, autonomy, sense of
      belonging and social bonding. Yet what restricts this participation-intervention
      methods, cognitive impairment, or other individuals in the participant's
      environment? This study documents stakeholders', volunteers' and users'
      perceptions of people with CI in community recreation centres (CRC). Six focus
      groups (n = 44) in Montreal, Quebec City and Drummondville highlighted some
      issues concerning this subject. Although sympathetic to a society where people
      with multiple weaknesses coexist, participants are not convinced of the need to
      include those whose memory and judgment are failing. The integration of people
      with CI includes relational and organizational challenges and questions our
      relationship to cognitive aging and performance values in an inclusive
      environment.

PMID- 29019296
TI  - Addiction to death.

PMID- 29019295
TI  - EXPLORING VALUES OF HEALTH TECHNOLOGY ASSESSMENT AGENCIES USING REFLECTIVE
      MULTICRITERIA AND RARE DISEASE CASE.
AB  - OBJECTIVES: Tackling ethical dilemmas faced by reimbursement decision makers
      requires deeper understanding of values on which health technology assessment
      (HTA) agencies are founded and how trade-offs are made. This was explored in this
      study including the case of rare disease. METHODS: Representatives from eight HTA
      explored values on which institutions are founded using a narrative approach and
      reflective multicriteria (developed from EVIDEM, criteria derived from ethical
      imperatives of health care). Trade-offs between criteria and the impact of
      incorporating defined priorities (including for rare diseases) were explored
      through a quantitative values elicitation exercise. RESULTS: Participants
      reported a diversity of substantive and procedural values with a common emphasis
      on scientific excellence, stakeholder involvement, independence, and
      transparency. Examining the ethical imperatives behind EVIDEM criteria was found
      to be useful to further explore substantive values. Most criteria were deemed to
      reflect institutions' values, while 70 percent of the criteria were reported by
      at least half of participants to be considered formally by their institutions.
      The quantitative values elicitation highlighted the difficulty to balance
      imperatives of "alleviating or preventing patient suffering," "serving the whole
      population equitably," "upholding healthcare system sustainability," and "making
      decisions informed by evidence and context" but may help share the ethical
      reasoning behind decisions. Incorporating "Priorities" (including for rare
      diseases) helped reveal trade-offs from other criteria and their underlying
      ethical imperatives. CONCLUSIONS: Reflective multicriteria are useful to explore
      substantive values of HTAs, reflect how these values and their ethical
      underpinnings can be operationalized into criteria, and explore the ethical
      reasoning at the heart of the healthcare debate.

PMID- 29019298
TI  - A learned artisan debates the system of the world: Le Clerc versus Mallemant de
      Messange.
AB  - Sebastien Le Clerc (1637-1714) was the most renowned engraver of Louis XIV's
      France. For the history of scientific publishing, however, Le Clerc represents a
      telling paradox. Even though he followed a traditional route based on classic
      artisanal training, he also published extensively on scientific topics such as
      cosmology and mathematics. While contemporary scholarship usually stresses the
      importance of artisanal writing as a direct expression of artisanal experience
      and know-how, Le Clerc's publications, and specifically the work on cosmology in
      his Systeme du monde (1706-1708), go far beyond this. By reconstructing the
      debate between Le Clerc and the professor Mallemant de Messange on the authorship
      of this 'system of the world', this article argues that Le Clerc's involvement in
      publishing ventures shaped his identity both as an artisan and as a scientific
      author. Whereas the Scientific Revolution supposedly heralded a change from the
      world of 'more or less' to the 'world of precision', this article shows how an
      artisan could be more 'precise' than the learned scholar whose claims he
      disputed, and points to the importance of the literary field as a useful lens for
      observing the careers of early modern scientific practitioners.

PMID- 29019297
TI  - REDUCING POTENTIALLY INAPPROPRIATE PRESCRIBING FOR OLDER PEOPLE IN PRIMARY CARE:
      COST-EFFECTIVENESS OF THE OPTI-SCRIPT INTERVENTION.
AB  - OBJECTIVES: This study examines the cost-effectiveness of the OPTI-SCRIPT
      intervention on potentially inappropriate prescribing in primary care. METHODS:
      Economic evaluation, using incremental cost-effectiveness and cost utility
      analyses, conducted alongside a cluster randomized controlled trial of twenty-one
      general practices and 196 patients, to compare a multifaceted intervention with
      usual practice in primary care in Ireland. Potentially inappropriate
      prescriptions (PIPs) were determined by a pharmacist. Incremental costs, PIPs,
      and quality-adjusted life-years (QALYs) at 12-month follow-up were estimated
      using multilevel regression. Uncertainty was explored using cost-effectiveness
      acceptability curves. RESULTS: The intervention was associated with a
      nonsignificant mean cost increase of ?407 (95 percent CIs, -357-1170), a
      significant mean reduction in PIPs of 0.379 (95 percent CI, 0.092-0.666), and a
      nonsignificant mean increase in QALYs of 0.013 (95 percent CIs, -0.016-0.042).
      The incremental cost per PIP avoided was ?1,269 (95 percent CI, -1400-6302) and
      the incremental cost per QALY gained was ?30,535 (95 percent CI, -334,846
      289,498). The probability of the intervention being cost-effective was 0.602 at a
      threshold value of ?45,000 per QALY gained and was at least 0.845 at threshold
      values of ?2,500 per PIP avoided and higher. CONCLUSIONS: While the OPTI-SCRIPT
      intervention was effective in reducing potentially inappropriate prescribing in
      primary care in Ireland, our findings highlight the uncertainty with respect to
      its cost-effectiveness. Further studies are required to explore the health and
      economic implications of interventions targeting potentially inappropriate
      prescribing.

PMID- 29019300
TI  - The politics of cognition: liberalism and the evolutionary origins of Victorian
      education.
AB  - In recent years the historical relationship between scientific experts and the
      state has received increasing scrutiny. Such experts played important roles in
      the creation and regulation of environmental organizations and functioned as
      agents dispatched by politicians or bureaucrats to assess health-related problems
      and concerns raised by the public or the judiciary. But when it came to making
      public policy, scientists played another role that has received less attention.
      In addition to acting as advisers and assessors, some scientists were
      democratically elected members of local and national legislatures. In this essay
      I draw attention to this phenomenon by examining how liberal politicians and
      intellectuals used Darwinian cognitive science to conceptualize the education of
      children in Victorian Britain.

PMID- 29019299
TI  - Additional mechanism for left ventricular dysfunction: chronic pulmonary
      regurgitation decreases left ventricular preload in patients with tetralogy of
      Fallot.
AB  - BACKGROUND: Right ventricular dysfunction in patients with tetralogy of Fallot
      and significant pulmonary regurgitation may lead to systolic dysfunction of the
      left ventricle due to altered ventricular interaction. We were interested in
      determining whether chronic pulmonary regurgitation affects the preload of the
      left ventricle. In addition, we wanted to study whether severe chronic pulmonary
      regurgitation would alter the preload of the left ventricle when compared with
      patients having preserved pulmonary valve annulus. METHODS: The study group
      comprised 38 patients with tetralogy of Fallot who underwent surgical repair
      between 1990 and 2003. Transannular patching was required in 21 patients to
      reconstruct the right ventricular outflow tract. Altogether, 48 age- and gender
      matched healthy volunteers were recruited. Cardiac MRI was performed on all study
      patients to assess the atrial and ventricular volumes and function. RESULTS:
      Severe pulmonary regurgitation (>30 ml/m2) was present in 13 patients, of whom 11
      had a transannular patch, but only two had a preserved pulmonary valve annulus.
      The ventricular preload volumes from both atria were significantly reduced in
      patients with severe pulmonary regurgitation, and left ventricular stroke volumes
      (44.1+/-4.7 versus 58.9+/-10.7 ml/m2; p<0.0001) were smaller compared with that
      in patients with pulmonary regurgitation <30 ml/m2 or in controls. CONCLUSIONS:
      In patients with tetralogy of Fallot, severe pulmonary regurgitation has a
      significant effect on volume flow through the left atrium. Reduction in left
      ventricular preload volume may be an additional factor contributing to left
      ventricular dysfunction.

PMID- 29019301
TI  - Validation of the Gratitude Questionnaire in Filipino Secondary School Students.
AB  - Most studies have assessed the psychometric properties of the Gratitude
      Questionnaire - Six-Item Form (GQ-6) in the Western contexts while very few
      research has been generated to explore the applicability of this scale in non
      Western settings. To address this gap, the aim of the study was to examine the
      factorial validity and gender invariance of the Gratitude Questionnaire in the
      Philippines through a construct validation approach. There were 383 Filipino high
      school students who participated in the research. In terms of within-network
      construct validity, results of confirmatory factor analyses revealed that the
      five-item version of the questionnaire (GQ-5) had better fit compared to the
      original six-item version of the gratitude questionnaire. The scores from the GQ
      5 also exhibited invariance across gender. Between-network construct validation
      showed that gratitude was associated with higher levels of academic achievement
      (beta = .46, p <.001), autonomous motivation (beta = .73, p <.001), and
      controlled motivation (beta = .28, p <.01). Conversely, gratitude was linked to
      lower degree of amotivation (beta = -.51, p <.001). Theoretical and practical
      implications are discussed.

PMID- 29019302
TI  - Education and Successful Aging Trajectories: A Longitudinal Population-Based
      Latent Variable Modelling Analysis.
AB  - As the population ages, interest is increasing in studying aging well. However,
      more refined means of examining predictors of biopsychosocial conceptualizations
      of successful aging (SA) are required. Existing evidence of the relationship
      between early-life education and later-life SA is unclear. The Successful Aging
      Index (SAI) was mapped onto the Cognitive Function and Aging Study (CFAS), a
      longitudinal population-based cohort (n = 1,141). SAI scores were examined using
      growth mixture modelling (GMM) to identify SA trajectories. Unadjusted and
      adjusted (age, sex, occupational status) ordinal logistic regressions were
      conducted to examine the association between trajectory membership and education
      level. GMM identified a three-class model, capturing high, moderate, and low
      functioning trajectories. Adjusted ordinal logistic regression models indicated
      that individuals in higher SAI classes were significantly more likely to have
      higher educational attainment than individuals in the lower SAI classes. These
      results provide evidence of a life course link between education and SA.

PMID- 29019303
TI  - Loneliness, Sociodemographic and Mental Health Variables in Spanish Adults over
      65 Years Old.
AB  - Loneliness is a risk factor for morbidity as well as mortality. Older people are
      more vulnerable to feeling alone due to age-associated changes and losses they
      might experience. This study aimed to analyze sociodemographic, psychosocial, and
      mental health variables related to loneliness in the elderly. A random sample of
      419 people over 65 years old from the Community of Madrid was used. The UCLA
      Loneliness Scale, the CIDI65+ Diagnostic Interview, and the WHOQOL-BREF Quality
      of Life Measure were administered. A regression p model was estimated to identify
      the variables that best predict loneliness associated with old age. Loneliness
      associated variables included living alone t(161.41) = 2.07; p < .040, marital
      status F(5, 404) = 4.52; p < .001, frequency of economic problems F(1, 408 ) =
      4.86; p < .028, quality of life F(4, 405) = 7.36; p < .001, satisfaction with
      life F(4, 405) = 3.80; p < .005, satisfaction with social relationships F(4, 405)
      = 19.50; p < .001, presence of a mental disorder (t(98.70) = 2.92; p < .004), and
      having an anxiety disorder (t(51.11) = 2.19; p < .033). The results presented in
      this paper highlight some predictors of loneliness in older people that could be
      useful in intervention, to minimize harmful conditions that can lead to
      loneliness in people over 65.

PMID- 29019304
TI  - Evaluation de la culture de securite en Etablissement d'Hebergement pour
      Personnes Agees Dependantes (EHPAD): adaptation francaise du questionnaire
      Nursing Home Survey on Patient Safety Culture.
AB  - The objective was to translate into French the American questionnaire "Nursing
      Home Survey on Patient Safety Culture" and to test the feasibility of its use in
      a sample of nursing homes. The questionnaire was translated by a
      multidisciplinary group of six experts and tested on a sample of people working
      in nursing homes. The questionnaire was then administered in five nursing homes.
      A first version of the French NHSPSC is proposed in this article. Despite
      similarities between items and ceiling effect for one item, the choices made were
      conservative to allow international comparisons. The administration of the
      questionnaire in five nursing homes confirmed the feasibility of the approach,
      with a participation of more than 50 per cent. This work made a French version of
      the NHSPSC available and confirmed that it is a feasible method for evaluating
      safety culture in nursing homes.

PMID- 29019305
TI  - How can Academic Context Variables Contribute to the Personal Well-Being of
      Higher Education Students?
AB  - This study analyzed the influence of perceived time pressure, role clarity,
      working conditions and peer social support on the personal well-being
      (subjective, psychological and social well-being) of higher education students,
      in a sample of 128 Portuguese students from the University of Lisbon. A model was
      proposed which predicts a negative influence of time pressure and a positive
      influence of role clarity, working conditions and peer social support on
      students' personal well-being, throughout the academic year. Data was collected
      by means of a longitudinal design, at the beginning and end of the academic year,
      through self-report questionnaires. Structural equation models were used to
      analyze cross-sectional and cross-lagged relations among the variables. At cross
      sectional level, results revealed a good fit to data (CFI = .928; IFI = .931;
      RMSEA = .060) illustrating that the perception of academic context variables was
      related to well-being dimensions. At longitudinal level, however, cross-lagged
      models did not fit so well to the data (CFI = .863; IFI = .869; RMSEA = .058)
      with both perceptions of time pressure (beta = .167; p = .037) and role clarity
      (beta = -.288; p = .031) significantly predicting well-being, but not in the
      expected direction, encouraging the accomplishment of studies to further a
      broader understanding of higher education students' well-being and its
      predictors. Implications for higher education scholars and practitioners and
      suggestions for future research are discussed.

PMID- 29019306
TI  - Detection of a chikungunya outbreak in Central Italy, August to September 2017.
AB  - An autochthonous chikungunya outbreak is ongoing near Anzio, a coastal town in
      the province of Rome. The virus isolated from one patient and mosquitoes lacks
      the A226V mutation and belongs to an East Central South African strain. As of 20
      September, 86 cases are laboratory-confirmed. The outbreak proximity to the
      capital, its late summer occurrence, and diagnostic delays, are favouring
      transmission. Vector control, enhanced surveillance and restricted blood
      donations are being implemented in affected areas.

PMID- 29019308
TI  - In the national epidemiological bulletins - a selection from recent issues.

PMID- 29019307
TI  - Control measures following a case of imported Lassa fever from Togo, North Rhine
      Westphalia, Germany, 2016.
AB  - In a patient transferred from Togo to Cologne, Germany, Lassa fever was diagnosed
      12 days post mortem. Sixty-two contacts in Cologne were categorised according to
      the level of exposure, and gradual infection control measures were applied. No
      clinical signs of Lassa virus infection or Lassa specific antibodies were
      observed in the 62 contacts. Thirty-three individuals had direct contact to
      blood, other body fluids or tissue of the patients. Notably, with standard
      precautions, no transmission occurred between the index patient and healthcare
      workers. However, one secondary infection occurred in an undertaker exposed to
      the corpse in Rhineland-Palatinate, who was treated on the isolation unit at the
      University Hospital of Frankfurt. After German authorities raised an alert
      regarding the imported Lassa fever case, an American healthcare worker who had
      cared for the index patient in Togo, and who presented with diarrhoea, vomiting
      and fever, was placed in isolation and medevacked to the United States. The event
      and the transmission of Lassa virus infection outside of Africa underlines the
      need for early diagnosis and use of adequate personal protection equipment (PPE),
      when highly contagious infections cannot be excluded. It also demonstrates that
      larger outbreaks can be prevented by infection control measures, including
      standard PPE.

PMID- 29019309
TI  - Management of a Lassa fever outbreak, Rhineland-Palatinate, Germany, 2016.
AB  - Due to rapid diagnosis and isolation of imported cases, community outbreaks of
      viral haemorrhagic fevers (VHF) are considered unlikely in industrialised
      countries. In March 2016, the first documented locally acquired case of Lassa
      fever (LF) outside Africa occurred, demonstrating the disease's potential as a
      cross-border health threat. We describe the management surrounding this case of
      LF in Rhineland-Palatinate - the German federal state where secondary
      transmission occurred. Twelve days after having been exposed to the corpse of a
      LF case imported from Togo, a symptomatic undertaker tested positive for Lassa
      virus RNA. Potential contacts were traced, categorised based on exposure risk,
      and monitored. Overall, we identified 21 contact persons with legal residency in
      Rhineland-Palatinate: seven related to the index case, 13 to the secondary case,
      and one related to both. The secondary case received treatment and recovered.
      Five contacts were quarantined and one was temporarily banned from work. No
      further transmission occurred. Based on the experience gained during the outbreak
      and a review of national and international guidelines, we conclude that exposure
      risk attributable to corpses may currently be underestimated, and we present
      suggestions that may help to improve the anti-epidemic response to imported VHF
      cases in industrialised countries.

PMID- 29019310
TI  - Lessons learnt from imported cases and onward transmission of Lassa fever in
      Europe support broader management of viral haemorrhagic fevers.

PMID- 29019312
TI  - Widespread distribution of mcr-1-bearing bacteria in the ecosystem, 2015 to 2016.
AB  - The recently discovered colistin resistance-encoding element, mcr-1, adds to the
      list of mobile resistance genes whose products rapidly erode the antimicrobial
      efficacy of not only the commonly used antibiotics, but also the last line agents
      of carbapenems and colistin. The relative prevalence of mcr-1-bearing strains in
      various ecological niches including 1,371 food samples, 480 animal faecal
      samples, 150 human faecal samples and 34 water samples was surveyed using a novel
      in-house method. Bacteria bearing mcr-1 were commonly detected in water (71% of
      samples), animal faeces (51%), food products (36%), and exhibited stable carriage
      in 28% of human subjects surveyed. Such strains, which exhibited variable
      antibiotic susceptibility profiles, belonged to various Enterobacteriaceae
      species, with Escherichia coli being the most dominant in each specimen type. The
      mcr-1 gene was detectable in the chromosome as well as plasmids of various sizes.
      Among these, two conjugative plasmids of sizes ca 33 and ca 60 kb were found to
      be the key vectors that mediated mcr-1 transmission in organisms residing in
      various ecological niches. The high mcr-1 carriage rate in humans found in this
      study highlights the importance of continued vigilance, careful antibiotic
      stewardship, and the development of new antimicrobials.

PMID- 29019313
TI  - Preliminary report of an autochthonous chikungunya outbreak in France, July to
      September 2017.
AB  - In August 2017, an autochthonous chikungunya case was reported in south-east
      France. By mid-September, eight additional autochthonous cases were found in the
      index case's neighbourhood, where the chikungunya virus vector Aedes albopictus
      was observed. Genomic characterisation identified an East-Central South African
      (ECSA) lineage strain, probably from the Central African region and carrying an
      adaptive mutation facilitating transmission by Ae. albopictus. The event confirms
      we need early case detection and response to contain chikungunya in Europe.

PMID- 29019314
TI  - Authors' reply: Geographic resolution of surveillance data and influenza
      prevention in large countries.

PMID- 29019316
TI  - Letter to the editor: Sampling bias should be minimised when analysing influenza
      transmission zones involving very large countries.

PMID- 29019315
TI  - Infectious disease screening in asylum seekers: range, coverage and economic
      evaluation in Germany, 2015.
AB  - Screening asylum seekers for infectious diseases is widely performed, but
      economic evaluations of such are scarce. We performed a policy analysis and
      economic evaluation of such screening in Germany, and analysed the effect of
      screening policies on cost differences between federal states. Of the 16 states,
      screening was compulsory for tuberculosis (TB) in asylum seekers >= 16 years of
      age in all states as well as in children < 16 years of age and pregnant women in
      six states, hepatitis B and enteropathogens in three, syphilis in two and human
      immunodeficiency virus (HIV) in one state. Of 441,899 asylum seekers, 88.0% were
      screened for TB, 22.9% for enteropathogens, 16.9% for hepatitis B, 13.1% for
      syphilis and 11.3% for HIV. The total costs for compulsory screening in 2015 were
      10.3 million euros (EUR). Costs per case were highest for infections with
      Shigella spp. (80,200 EUR), Salmonella spp. (8,000 EUR), TB in those >= 16 years
      of age (5,300 EUR) and syphilis (1,150 EUR). States with extended screening had
      per capita costs 2.84 times those of states that exclusively screened for TB in
      asylum seekers >= 16 years of age (p < 0.0001, 95% confidence interval (CI): 1.96
      4.10). Screening practices in Germany entailed high costs; evidence-based
      approaches to infectious disease screening are needed.

PMID- 29019318
TI  - Addendum for Euro Surveill. 2017;22(8).

PMID- 29019317
TI  - PRECEPT: an evidence assessment framework for infectious disease epidemiology,
      prevention and control.
AB  - Decisions in public health should be based on the best available evidence,
      reviewed and appraised using a rigorous and transparent methodology. The Project
      on a Framework for Rating Evidence in Public Health (PRECEPT) defined a
      methodology for evaluating and grading evidence in infectious disease
      epidemiology, prevention and control that takes different domains and question
      types into consideration. The methodology rates evidence in four domains: disease
      burden, risk factors, diagnostics and intervention. The framework guiding it has
      four steps going from overarching questions to an evidence statement. In step 1,
      approaches for identifying relevant key areas and developing specific questions
      to guide systematic evidence searches are described. In step 2, methodological
      guidance for conducting systematic reviews is provided; 15 study quality
      appraisal tools are proposed and an algorithm is given for matching a given study
      design with a tool. In step 3, a standardised evidence-grading scheme using the
      Grading of Recommendations Assessment, Development and Evaluation Working Group
      (GRADE) methodology is provided, whereby findings are documented in evidence
      profiles. Step 4 consists of preparing a narrative evidence summary. Users of
      this framework should be able to evaluate and grade scientific evidence from the
      four domains in a transparent and reproducible way.

PMID- 29019319
TI  - The Asymptomatic Carotid Surgery Trial-2 (ACST-2): an ongoing randomised
      controlled trial comparing carotid endarterectomy with carotid artery stenting to
      prevent stroke.
AB  - BACKGROUND: A successful open surgical operation to remove atheromatous carotid
      artery narrowing that has not yet caused a stroke (asymptomatic carotid stenosis)
      carries some procedural risk but, if completed successfully, halves patients'
      future annual stroke risk for at least 10 years. A newer, less invasive
      alternative is carotid stenting, which also carries some procedural risk,
      especially if the carotid lesion has recently given rise to a stroke (symptomatic
      carotid stenosis). For both surgery and stenting, improvements in technique (and
      in medication) have reduced risk. Early studies showed that treating carotid
      narrowing by stenting, particularly for symptomatic lesions, caused more
      procedural minor strokes than surgery, but more recent trials in symptomatic and
      in asymptomatic patients found that both procedures might now be equally safe and
      effective. However, low patient numbers, short follow-up of the long-term effects
      on stroke rates and wide confidence intervals mean that worldwide uncertainty
      persists between carotid surgery and carotid stenting, and national and
      international guidelines remain unclear as to which is generally better.
      OBJECTIVES: The second Asymptomatic Carotid Surgery Trial (ACST-2) compares
      carotid endarterectomy (CEA) with carotid artery stenting (CAS) directly,
      randomising patients with asymptomatic carotid stenosis for whom a carotid
      procedure is considered definitely necessary; both procedures seem anatomically
      feasible, and there is substantial uncertainty as to which of the two would be
      better for such individuals. Although it will compare procedural risks, the
      trial's primary aim is to compare the long-term durability of protection against
      strokes occurring in the years post procedure due to any remaining or recurrent
      carotid disease. DESIGN: Randomised controlled trial comparing CEA with CAS.
      SETTING: Hospitals in the UK and worldwide, in which carotid procedures are
      common. PARTICIPANTS: Men and women with severely stenotic atherosclerotic
      carotid artery disease, with or without previous stroke but with no recent
      symptoms from the randomised artery. INTERVENTIONS: CEA and CAS. OUTCOMES: (1)
      Periprocedural risk defined as myocardial infarction, stroke or death within 30
      days after the randomised procedure and (2) long-term rates of disabling or fatal
      stroke during follow-up of patients. MEASUREMENT OF COSTS AND OUTCOMES:
      Measurement of intervention costs and stroke costs (periprocedural and during
      follow-up) and of quality of life [EuroQol-5 Dimensions (EQ-5D(r))] for patients
      in the top six recruiting countries (UK, Italy, Belgium, Germany, Serbia and
      Sweden), who currently constitute 85% of those randomised. PROGRESS SO FAR: By
      the end of March 2016, ACST-2 had included 2125 patients, nearly two-thirds of
      the planned recruitment of 3600; 1061 were randomly allocated to CEA and 1064 to
      CAS. CONCLUSIONS: Further funding has been secured and recruitment continues,
      with completion anticipated by the end of 2019. ACST-2 will report initial
      results in 2021. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21144362.
      FUNDING: This project was funded by the National Institute for Health Research
      (NIHR) Health Technology Assessment programme and will be published in full in
      Health Technology Assessment; Vol. 21, No. 57. See the NIHR Journals Library
      website for further project information. Funding was also received from BUPA
      Foundation [BUPAF/33(a)/05].

PMID- 29019320
TI  - Distinct cellular and molecular mechanisms for beta3 adrenergic receptor-induced
      beige adipocyte formation.
AB  - Beige/brite adipocytes are induced within white adipose tissues (WAT) and, when
      activated, consume glucose and fatty acids to produce heat. Classically, two
      stimuli have been used to trigger a beiging response: cold temperatures and beta3
      adrenergic receptor (Adrb3) agonists. These two beiging triggers have been used
      interchangeably but whether these two stimuli may induce beiging differently at
      cellular and molecular levels remains unclear. Here, we found that cold-induced
      beige adipocyte formation requires Adrb1, not Adrb3, activation. Adrb1 activation
      stimulates WAT resident perivascular (Acta2+) cells to form cold-induced beige
      adipocytes. In contrast, Adrb3 activation stimulates mature white adipocytes to
      convert into beige adipocytes. Necessity tests, using mature adipocyte-specific
      Prdm16 deletion strategies, demonstrated that adipocytes are required and are
      predominant source to generate Adrb3-induced, but not cold-induced, beige
      adipocytes. Collectively, we identify that cold temperatures and Adrb3 agonists
      activate distinct cellular populations that express different beta-adrenergic
      receptors to induce beige adipogenesis.

PMID- 29019323
TI  - Diet, Physical Activity, Marital Status and Risk of Cancer: A Case Control Study
      of Adults from Riyadh, Saudi Arabia.
AB  - OBJECTIVES: We aimed to compare the dietary habits, engagement in various sports,
      smoking habits, marital status and other demographic characteristics, between
      cancer patients and healthy adults (control) at our institute, Riyadh, Saudi
      Arabia. PATIENTS AND METHODS: A cross-sectional descriptive study was conducted
      on 500 participants (237 cancer patients and 263 healthy adults). A well
      structured questionnaire was given to these participants regarding the life
      style, dietary habits, and marital status through interviews. RESULTS: Mean age
      of whole cohort was 39.3 years (range: 14-85). Among the cancer patients, breast
      cancer was predominant (45.6%). Compared to controls, higher percentage of
      married (72.6% vs. 55.5%) and divorced (10.2% vs.4.2%) was noticed in cancer
      patients (P = 0.002). In cancer patients, majority were unemployed (housewives =
      49.3%; retired = 16.0%) as compared to controls (housewives = 14.1%; retired =
      2.0%) P = 0.0001. Use of computer laptops/tablets and internet surfing was
      significantly higher in controls as compared to cancer patients (80.3% vs. 42.2%)
      P = 0.0001. Similarly, cancer patients started smoking at early age and were
      relatively heavy smokers with P = 0.03 and P = 0.001 respectively. Cancer
      patients consumed < 3 cups of coffee/day as compared to control (42.4% vs. 21.5%)
      P = 0.02. More cancer patients got married at early age between 11-20 years
      (58.7% vs. 37.7%) P = 0.01. CONCLUSION: Unemployment, marital status, lack of
      nutritional knowledge through internet, heavy smoking, heavy coffee consumption
      and early age at marriage were associated with the risk of various cancers in
      both genders.

PMID- 29019324
TI  - Clinico-hematological Profile of 184 Patients with Non-Hodgkin's Lymphoma: An
      Experience from Southern Pakistan.
AB  - BACKGROUND: Non-Hodgkin lymphoma (NHL) is a diverse group of lymphoma comprises
      of divergent tumors with paradoxical clinical behaviors and potential difference
      in response to therapy. We conducted a data-base analysis on NHL patients to
      evaluate the clinico-epidemiological features and WHO spectrum of NHL in
      Pakistani patients. MATERIALS AND METHODS: This descriptive study was conducted
      over a period of 5 years from January 2011 to December 2015 at Hematology
      department of Liaquat National Hospital. All NHL cases were diagnosed by
      morphology on H&E sections and Immunohistochemical profile according to WHO
      classification of lymphoid neoplasms. RESULTS: 184 histopathologically confirmed
      cases of NHL were identified. There were 139 males and 45 females, with a male to
      female ratio of 3: 1. The mean age was 48.5+/-16.0 years with the median age of
      50 years. B symptoms were present in 80.4% of patients. Lymph node enlargement
      was present in 71.1% of the cases. 168 patients ad B-cell lymphoma (91.3%) and 16
      patients had T-cell (8.6%) lymphoma. Overall 158 (85.8%) patients had aggressive
      lymphoma. Histopathologically, Diffuse large B-cell lymphoma constituted major
      subtype in 67.9%, followed by follicular lymphoma in 7.6% patients. Marginal
      lymphoma in 3.8%patients, 3.2% patients had mantle cell, 2.7% patients of
      anaplastic large cell and 2.1% patients each for Burkitt's lymphoma and T-cell
      rich lymphoma. In T cell neoplasm, peripheral T cell lymphoma and adult T cell
      lymphoma are the main variants accountable in 4.3% and 3.2% respectively.
      CONCLUSIONS: B cell lymphoma is more frequent than T cell lymphoma with diffuse
      large B-cell lymphoma being the commonest NHL. Our analysis shows that
      clinicopathological features of NHL are comparable to published data. However,
      aggressive lymphoma and predominance of B symptoms are more frequently seen.

PMID- 29019325
TI  - Ambiguity of Whole Body PET CT Scans in Diagnosis of Co-existing Tuberculosis and
      Malignancy: Is Histopathological Confirmation Mandatory?
AB  - INTRODUCTION: Whole body PET CT is an important investigation tool in malignancy
      patients and helps in ascertaining the metabolic activity and exact stage of the
      disease. However, like any other investigation, false positive results do exist
      and certain diseases other than cancer may show increased uptake. Hence, a
      careful evaluation of PET CT and clinical correlation in malignancy patients is a
      must to accomplish the suitable treatment. METHODS: In this retrospective
      observational study, seven cases of cancer with concomitant tuberculosis were
      included. All the patients were proven malignancy patients with advanced or
      metastatic stage. On clinical suspicion, a tissue diagnosis was obtained which
      led to change in staging as well as management of the patients. RESULTS: Seven
      patients were having primary diagnosis of carcinoma breast, carcinoma esophagus,
      coepidermoid carcinoma of submandibular salivary gland, carcinoma tongue,
      squamous cell carcinoma skin, carcinoma cervix and carcinoma endometrium. They
      showed FDG uptake at distant sites leading to upstaging of disease. On
      histopathological examination, lymph nodal mass reported granulomatous
      lymphadenitis, leading to change of overall staging and management of the
      patients. DISCUSSION AND CONCLUSIONS: Whole Body PET CT scan may produce false
      positive results and upstage the disease. It should be evaluated and interpreted
      with caution in cases of doubtful findings and any abnormal FDG accumulation in
      PET CT scan at unusual locations should be evaluated carefully and confirmed
      histopathologically.

PMID- 29019327
TI  - Disclosure of Adverse Cancer News: The Public's Perspective in a Middle Eastern
      Country.
AB  - OBJECTIVES: The disclosure to patients of unfavorable news related to cancer
      remains a controversial issue in the Middle East. This study investigated the
      perspective of the public in Saudi Arabia regarding the disclosure of unfavorable
      cancer-related news. METHODS: A convenience sample of 103 adult noncancer
      patients attending a family medicine clinic were asked to respond to 9 closed
      ended questions. These questions reflected possible adverse news from the time of
      diagnosis until the end of life. The primary endpoint was an affirmative response
      (AR) to =7 questions (AR=7) indicating a preference to be informed of the
      majority (=78%) of adverse situations. RESULTS: One hundred individuals completed
      the questionnaire. Of these, 56 (56%) were male, and 44 (44%) were female. The
      median age was 32 years (18-75 years). Different questions were answered
      affirmatively by 76-99% of the responders. An AR=7 was reported by 83% of the
      responders. There was no statistically significant correlation between an AR=7
      and age, gender or employment status (Chi-squared P values: 0.731, 0.427, and
      0.148, respectively). There was a trend towards an AR=7 among those with higher
      levels of education compared to those with a lower level of education (88% and
      73%, respectively, P=0.055). CONCLUSION: The results of this study suggest that
      the majority of Saudi Arabians prefer to be informed of most of the adverse
      health-related news if diagnosed with cancer. These results should encourage
      physicians to keep cancer patients informed of their health-related events unless
      the patient indicates otherwise.

PMID- 29019326
TI  - Epidemiology and Outcomes with Platinum-Based Chemotherapy in Recurrent or
      Metastatic Carcinoma Cervix in a Developing Country: Experience from a Tertiary
      Oncology Centre in Southern India.
AB  - INTRODUCTION: Carcinoma cervix is the leading cause of cancer in Indian women.
      Recurrent/metastatic cervix is the most aggressive form of the disease. There is
      paucity of data in this setting in Indian women regarding outcomes with
      palliative chemotherapy. METHODS: We retrospectively analyzed hospital registry
      data between January 2013 and December 2014 for recurrent/metastatic carcinoma
      cervix patients who were planned for palliative chemotherapy and assessed their
      demographic parameters, response and survival outcomes with chemotherapy.
      RESULTS: We identified 165 cases of recurrent/metastatic carcinoma cervix. Median
      age at presentation was 48 years. Most common symptoms at presentation were
      bleeding or white discharge per vagina and lower abdominal pain. Majority of the
      patients were multiparous. Histologically squamous cell carcinoma was found most
      commonly (93.3%) with adenocarcinoma and adenosquamous carcinoma being
      exceedingly uncommon (3.63% each). 38% of patients were upfront metastatic while
      rest were recurrent disease. Most common sites of metastasis were retroperitoneal
      lymph nodes (21.21%), liver (11.51%), lung (9.69%), supraclavicular lymph nodes
      (8.48%) and bone (7.27%). After a median of 6 cycles of paclitaxel and
      carboplatin based chemotherapy, overall response rate (ORR) was 26.7% with 10.5%
      complete remission (CR) and 16.4% partial remission (PR) rates. Median
      progression free survival (PFS) was 6 months while median overall survival (OS)
      was 11 months. CONCLUSION: Recurrent/metastatic cervical carcinoma is an
      aggressive disease. Our patients showed an ORR of 26.7% to palliative
      chemotherapy with median PFS of 6 months and median OS of 11 months. Further
      research is required related to novel targeted agents and nonplatinum doublets.

PMID- 29019321
TI  - Beyond excitation/inhibition imbalance in multidimensional models of neural
      circuit changes in brain disorders.
AB  - A leading theory holds that neurodevelopmental brain disorders arise from
      imbalances in excitatory and inhibitory (E/I) brain circuitry. However, it is
      unclear whether this one-dimensional model is rich enough to capture the multiple
      neural circuit alterations underlying brain disorders. Here, we combined
      computational simulations with analysis of in vivo two-photon Ca2+ imaging data
      from somatosensory cortex of Fmr1 knock-out (KO) mice, a model of Fragile-X
      Syndrome, to test the E/I imbalance theory. We found that: (1) The E/I imbalance
      model cannot account for joint alterations in the observed neural firing rates
      and correlations; (2) Neural circuit function is vastly more sensitive to changes
      in some cellular components over others; (3) The direction of circuit alterations
      in Fmr1 KO mice changes across development. These findings suggest that the basic
      E/I imbalance model should be updated to higher dimensional models that can
      better capture the multidimensional computational functions of neural circuits.

PMID- 29019328
TI  - Second Primary Tumors associated with Breast Cancer: Kuwait Cancer Control Center
      Experience.
AB  - OBJECTIVES: To review the clinico-epidemiologic characteristics of patients who
      presented with two or more primary cancers, one of which was breast cancer (BC)
      and to develop a follow-up program for the high risk patients. PATIENTS AND
      METHODS: Patients who were diagnosed with BC and one or more non breast cancer
      (NBC) were retrospectively reviewed. Medical files were retrieved and
      epidemiological as well as clinical data were analyzed. RESULTS: Sixty-two
      patients were retrieved. BC was the first primary in 26 patients while it was the
      second in 36 patients. Two were males and 60 were females. The median age was 48
      years and the median follow-up was 11.5 years. The median interval between the
      1st and 2nd primary was 6 years. The most commonly associated NBCs were colon and
      thyroid cancers, each accounts for 24% of cases followed by endometrial cancer,
      18%; Hodgkin's disease, 6.5%; renal and ovarian neoplasm and NHL, 5% each. Others
      included prostate, lung, cervical and gastric cancers, soft tissue sarcoma and
      osteosarcoma. Thyroid cancer was more common as first cancer while endometrial
      cancer was more as second cancer. All patients who developed BC following
      Hodgkin's disease had received chest irradiation. Seven patients developed 3rd
      primary (4 lung cancers, 2 NHL, and 1 AML). CONCLUSION: Patients who were
      diagnosed with BC should be screened for colon and endometrial cancer. Similarly,
      patients received chest irradiation at young age, and those diagnosed with
      thyroid or colon cancer should be screened for BC. Protocol of surveillance needs
      to be defined. Genetic counseling should be offered to individuals who have
      experienced multiple primary cancers particularly those with family history and
      young age of onset.

PMID- 29019322
TI  - Recruitment dynamics of ESCRT-III and Vps4 to endosomes and implications for
      reverse membrane budding.
AB  - The ESCRT machinery mediates reverse membrane scission. By quantitative
      fluorescence lattice light-sheet microscopy, we have shown that ESCRT-III
      subunits polymerize rapidly on yeast endosomes, together with the recruitment of
      at least two Vps4 hexamers. During their 3-45 s lifetimes, the ESCRT-III
      assemblies accumulated 75-200 Snf7 and 15-50 Vps24 molecules. Productive budding
      events required at least two additional Vps4 hexamers. Membrane budding was
      associated with continuous, stochastic exchange of Vps4 and ESCRT-III components,
      rather than steady growth of fixed assemblies, and depended on Vps4 ATPase
      activity. An all-or-none step led to final release of ESCRT-III and Vps4.
      Tomographic electron microscopy demonstrated that acute disruption of Vps4
      recruitment stalled membrane budding. We propose a model in which multiple Vps4
      hexamers (four or more) draw together several ESCRT-III filaments. This process
      induces cargo crowding and inward membrane buckling, followed by constriction of
      the nascent bud neck and ultimately ILV generation by vesicle fission.

PMID- 29019329
TI  - Implications of Observer Variation in Gleason Scoring of Prostate Cancer on
      Clinical Management: A Collaborative Audit.
AB  - BACKGROUND: Prostate cancer is the most frequently diagnosed cancer in men.
      Histological tumour grade is a strong predictor of outcome and helps determine
      what treatment options are offered. There are numerous studies on Inter-observer
      agreement/variability on prostate cancer grading. In this study, we were looking
      to establish if disconcordance between pathologists when grading prostate cancer,
      could affect treatment options offered to men. METHODS: In Greater Manchester
      West Cancer Sector, all prostate cancer biopsies undergo a central review by
      three pathologists with a special interest in urological pathology prior to
      referral for treatment at specialist centres. 96 prostate biopsies (from 48
      patients) from a District General Hospital were reviewed during a 6-month period
      (March 2014-September 2014). The original Gleason Score assigned was compared
      with the uropathologists consensus diagnosis established at the central review
      meeting. Any changes in patient risk and treatment plans were subsequently
      reviewed. RESULTS: Of the 96 biopsies discussed at central review meeting, 24
      (25%) biopsies from 19 patients underwent a change in Gleason grade and a
      subsequent change in risk for 13 (68%). Of the 19 patients, management plans
      could be affected for 9 patients (47%) and treatment options could potentially be
      affected for 5 (26%). CONCLUSION: This study shows that where disconcordance
      between pathologists is present, there is the potential to affect patient
      management. A central review process can help to minimize the effect over or
      undergrading can have on the patient and should be considered a necessary step in
      the management of prostate cancer.

PMID- 29019330
TI  - Squamous Cell Carcinoma of the Buccal Mucosa: A Single Institute Retrospective
      Analysis of Nodal Involvement and Survival.
AB  - BACKGROUND: The magnitude of head and neck (H&N) cancers in the Indian
      subcontinent is very high. Neck nodal involvement is indicative of higher stage
      and subsequent adverse prognosis when compared with node negative disease. The
      frequency of such spread is greater than 20% for most H&N squamous cell
      carcinomas (SCC). The purpose of this study was to analyze the pattern of nodal
      metastasis in patients presenting with SCC of buccal mucosa (BM) and correlate it
      with survival. PATIENTS AND METHODS: Ninety-nine cases of carcinoma BM who
      received post op radiotherapy were analyzed retrospectively. Medical records were
      reviewed and data collected from the hospital case files. Patients were analyzed
      for age and sex distribution, tumor staging, metastasis and overall survival.
      RESULTS: The majority of cases were T4 lesions (n=40, 40.40%), followed by T2
      lesions (n=35, 35.35%). T3 lesions constituted for 19.19% cases (n=19) while
      there were five cases (5.05%) of T1 lesions. 62 patients (62.62%) had positive
      neck nodes, with/without adverse pathologic features mandating post-operative
      radiotherapy, while 37 patients (37.37%) did not have any neck nodal involvement.
      The mean overall survival of the node negative patients (n=37) was 14.51 months
      (range 02-61 months) and was significantly more (p=0.03) than that of the node
      positive patients [10.82 months (range 01-35 months)]. A statistically
      significant difference in survival was also seen between the node negative
      patients and patients with >3 positive neck nodes (p=0.04). CONCLUSION: Neck
      nodal involvement in cases of carcinoma BM is an adverse prognostic indicator.
      The number of pathological positive neck nodes can be used as a predictor of
      treatment outcome.

PMID- 29019331
TI  - Clinical and Pathological Characteristics of Triple Positive Breast Cancer among
      Iraqi Patients.
AB  - BACKGROUND: Breast cancer is the most common malignancy affecting the Iraqi
      population and the leading cause of cancer related mortality among Iraqi women.
      It has been well documented that prognosis of patients depends largely upon the
      hormone receptor contents and HER-2 over expression of their neoplasm. Recent
      studies suggest that Triple Positive (TP) tumors, bearing the three markers, tend
      to exhibit a relatively favorable clinical behavior in which overtreatment is not
      recommended. AIM: To document the different frequencies of ER/PR/HER2 breast
      cancer molecular subtypes focusing on the Triple Positive pattern; correlating
      those with the corresponding clinico-pathological characteristics among a sample
      of Iraqi patients diagnosed with the disease. PATIENTS AND METHODS: This
      retrospective study involved 570 female patients diagnosed with breast cancer who
      visited the Main Referral Center for Early Detection of Breast Cancer and the
      National Cancer Research Center. The requested data was mainly extracted from an
      established information system database, developed by the principal author over a
      4-years period from 2012 to 2016. The registered information comprised data
      related to clinical presentation, diagnostic and pathologic findings. ER, PR and
      HER2 status were analyzed immunohistochemically and the detected profiles were
      correlated with the corresponding clinico-pathological characteristics. RESULTS:
      The rates of ER (+), PR (+) and HER-2 (+) tumors were 66.8%, 64% and 29.3%
      respectively. The tumor marker expression status was documented in eight
      subtypes; 83 cases (14.6%) of the examined breast carcinomas were categorized as
      ER+/PR+/HER2+ (Triple Positive/Luminal B), 89 cases (15.6%) were ER-/PR-/HER2-
      (Triple Negative), 241 (42.2%) were ER+/PR-/HER2- (Luminal A) while 67 (11.8%)
      showed ER-/PR-/HER2+ expression (HER-2 variant). No significant variations were
      noted when comparing age, menopausal status and tumor grade of Luminal B pattern
      to Luminal A and the rest of the studied subtypes. Although our data revealed a
      statistical difference with respect to the distribution of tumor types; where
      infiltrative ductal carcinoma constituted the major histology among patients with
      Triple Positive/Luminal B subtype (86.7% as compared to 67.6% in Luminal A),
      nevertheless, more than two third of those patients (67.4%) were diagnosed at
      earlier stages (I and II) compared to 55.2% of those in the remaining groups.
      CONCLUSIONS AND RECOMMENDATIONS: Our findings support the hypothesis that the
      Triple Positive subtype might be driven primarily by the hormone receptor status.
      Further comprehensive surveys are recommended to focus on the intrinsic
      interactions and tumor cell heterogeneity of that pattern to avoid overtreatment
      and predict accurate response to therapy.

PMID- 29019332
TI  - Pre-Treatment Nutritional Status and Radiotherapy Outcome in Patients with
      Locally Advanced Head and Neck Cancers.
AB  - AIM: Poor oral intake and associated nutritional depletion can affect treatment
      outcome in locally advanced head and neck cancers. The aim of this study was to
      evaluate the pre radiotherapy nutritional status as a predictor for response to
      radiotherapy treatment. PATIENTS AND METHODS: Fifty patients of locally advanced
      head and neck cancers undergoing radical chemoradiotherapy were evaluated in this
      prospective analysis. Patients were treated with definitive radiotherapy to a
      total dose of 60-70 Gy along with concurrent chemotherapy with injection
      Cisplatin 100mg/m2 delivered three weekly. The patients were evaluated for pre
      treatment nutritional status using the Patient-Generated Subjective Global
      Assessment (PG-SGA) questionnaire. The PG-SGA evaluation was completed just
      before starting radiotherapy treatment and scores correlated to treatment
      outcome. RESULTS: Forty-seven male and three female patients were evaluated in
      this analysis. The median PG-SGA score was 8 with a range from 2-14.Grade 3-4
      mucositis was seen in seven patients (21.8%) with PGSGA <9 compared to 55.5% in
      those with PG-SGA score = 9 (p=0.01). At the time of evaluation a complete
      response was seen in 16 patients (32%) with a PG-SGA score <9 compared to 4
      patients (8%) with a PGSGA =9 (p=0.05). The median survival was 16+/-2.8months
      (Median +/-S. Error) and 17+/-2.9 months in those with PG-SGA <9 and =9
      respectively (p=0.49, log rank). CONCLUSION: PG-SGA nutritional score <9 is
      associated with a better local control and acute toxicity profile in radically
      treated head and neck cancer patients.

PMID- 29019333
TI  - Evaluation of BRCA1 Large Genomic Rearrangements in Group of Egyptian Female
      Breast Cancer Patients Using MLPA.
AB  - INTRODUCTION: Breast cancer is one of the most widespread cancers affecting women
      all over the world. In Egypt, it is considered to be the first cause of
      malignancies among female. BRCA1 Large Genomic Rearrangements (LGRs) have been
      reported in hereditary breast families and occurs in considerable proportion of
      cases in various populations. OBJECTIVE AND METHODS: We investigated the
      incidence of BRCA1 LGRs in group of Egyptian females with breast cancer using
      Multiplex Ligation-dependent Probe Amplification (MLPA) assay. RESULTS: Thirty
      six female breast cancer patients were included in this study. There were no
      BRCA1 LGRs detected in the studied group of patients which does not coincide with
      other study that were done on a group of Egyptian female patients. DISCUSSION AND
      CONCLUSION: This variance may be due to the small number of the investigated
      patients in both studies, which is considered as a limitation. So, screening for
      LGRs of BRCA1 gene as well as other genes that may be involved in breast cancer
      such as BRCA2 and CHEK2 genes of a larger number of patients is recommended to
      get the actual prevalence of these gene in the Egyptian population to deliver a
      cost-effective primary approach for these patients.

PMID- 29019334
TI  - Brain Metastasis from Colorectal Adenocarcinoma: A Case Report.
AB  - Colorectal cancer (CRC) is the third leading cause of cancer death in the Western
      world, accounting for approximately 140,000 new cases and more than 51,000 deaths
      in 2010 in the United States. In Kuwait, CRC is the first most-diagnosed neoplasm
      among males and overall, the second leading cause of death from cancer. The 5
      year survival rate in 2002-2004 was 61% for men and 62% for women. Even after
      complete resection of the colorectal tumor, distant metastases have been noted to
      develop in 10%-15% of patients. Of all metastases, those to the liver were found
      in 20%-30% of cases, and to the lung, in 10%-20%; brain metastases are quite
      rare. The percentage of CRC patients developing brain metastases during the
      course of their disease is reported to range from 2% to 12%, but the effect of
      such metastases on the patient's prognosis is significant. With the advent of new
      targeted therapies and the resulting improvements in outcome for CRC patients,
      the management policy for brain metastases has changed. Regardless of the therapy
      used to address brain metastases, reported median survival ranges from 2.8 months
      to 6 months. We report a case of brain metastasis in a patient of primary
      colorectal adenocarcinoma. He was evaluated for convulsion, CT findings showed
      brain metastasis.

PMID- 29019335
TI  - Leiomyosarcoma of Penis: An Aggressive and Exceptionally Rare Entity.
AB  - Penile leiomyosarcoma is a very rare disease of penile mesenchymal tissue, most
      of them are of vascular origin and pathologically classified into the superficial
      and deep type. Because of the small number of cases reported so far, the
      conclusions about treatment and prognosis are equivocal. Here we report a case of
      40-year old patient who presented with leiomyosracoma of penis; despite adequate
      surgery patient developed local recurrence and distant metastasis indicating
      aggressive nature of leiomyosarcoma entity of penis.

PMID- 29019336
TI  - Chemotherapy-Induced Febrile Neutropenia in Solid Tumours.
AB  - Febrile neutropaenia (FN) is defined as an oral temperature of >38.3 degrees C or
      two consecutive readings of >38.0 degrees C for 2 hours and an absolute
      neutrophil count (ANC) of <0.5 * 109/l, or expected to fall below 0.5 * 109/l.
      Fever is one of the characteristic symptoms of FN and is usually associated with
      the presence of an infection caused by various microorganisms. The incidence and
      epidemiology of FN are variable based on different factors: (type of cancer, the
      age/sex of the patient, chemotherapy type /number of cycles). FN remains one of
      the most common and risky complications of chemotherapy which occurred within 6-8
      days with standard chemotherapy and it is occurred as about 7-8/1000 patients
      receiving treatment with chemotherapeutic agents. There is a clear relationship
      between the severity of neutropaenia (which directly influences the incidence of
      FN) and the intensity of chemotherapy. Currently, the different regimens are
      classified as producing a high risk (>20%), an intermediate risk (10%-20%) or a
      low risk (<10%) of FN. The causative organisms including either bacteria, fungi
      or viruses. The bacteria Gram-positive (currently dominating) and Gram-negative
      (Dominant in the 1970s), are usually the main microorganisms responsible for FN
      and cause complicated infections. Although the morbidity and mortality rates of
      FN have decreased over the years due to use of proper antibiotic treatment,
      preventive measures and use the standardrisk management plan as per guidelines
      but it is still one of oncological emergency. FN is responsible for considerable
      morbidity as 20%-30% of patient's present complications that require in-hospital
      management, with an overall in-hospital mortality of ~10%.

PMID- 29019337
TI  - Monte Carlo simulation of beta particle-induced bremsstrahlung doses.
AB  - It is well known that protection from the external irradiation produced by beta
      emitters is simpler than the corresponding shielding of radioactive sources that
      emit gamma radiation. This is caused by the relatively strong absorption (i.e.
      short range) of electrons in different materials. However, for strong beta
      sources specific attention should be paid to the bremsstrahlung radiation induced
      in the source encapsulation (matrix), especially for emitters with relatively
      high beta-endpoint energy (1 MeV) that are frequently used in nuclear medicine.
      In the present work, the bremsstrahlung spectra produced in various materials by
      the following beta emitters, Sr-90 (together with its daughter Y-90), P-32 and Bi
      210, were investigated by Monte Carlo simulations using Geant4 software. In these
      simulations, it is supposed that the point radioactive sources are surrounded by
      cylindrically shaped capsules made from different materials: Pb, Cu, Al, glass
      and plastic. For the case of Y-90(Sr-90) in cylindrical lead and aluminum
      capsules, the dimensions of these capsules have also been varied. The absorbed
      dose rates from bremsstrahlung radiation were calculated for cases where the
      encapsulated point source is placed at a distance of 30 mm from the surface of a
      water cylinder with a mass of 75 kg (approximately representing the human body).
      The bremsstrahlung dose rate and bremsstrahlung spectrum from the Y-90(Sr-90)
      point source encapsulated in an Al capsule were also measured experimentally and
      compared with the corresponding simulation results. In addition, the
      bremsstrahlung radiation risk for medical staff in therapies using Y-90 was
      considered in simulations, relating to finger dose as well as whole-body dose
      during preparation and injection of this radioisotope. The corresponding annual
      doses were obtained for medical workers for specified numbers of Y-90
      applications to patients.

PMID- 29019338
TI  - Reduced graphene oxide-germanium quantum dot nanocomposite: electronic, optical
      and magnetic properties.
AB  - Graphene provides numerous possibilities for structural modification and
      functionalization of its carbon backbone. Localized magnetic moments can, as
      well, be induced in graphene by the formation of structural defects which include
      vacancies, edges, and adatoms. In this work, graphene was functionalized using
      germanium atoms, we report the effect of the Ge ad atoms on the structural,
      electrical, optical and magnetic properties of graphene. Reduced graphene oxide
      (rGO)-germanium quantum dot nanocomposites of high crystalline quality were
      synthesized by the microwave-assisted solvothermal reaction. Highly crystalline
      spherical shaped germanium quantum dots, of diameter ranging between 1.6-9.0 nm,
      are anchored on the basal planes of rGO. The nanocomposites exhibit high
      electrical conductivity with a sheet resistance of up to 16 Omega sq-1. The
      electrical conductivity is observed to increase with the increase in Ge content
      in the nanocomposites. High defect-induced magnetization is attained in the
      composites via germanium adatoms. The evolution of the magnetic moments in the
      nanocomposites and the coercivity showed marked dependence on the Ge quantum dots
      size and concentration. Quantum confinement effects is evidenced in the UV-vis
      absorbance spectra and photoluminescence emission spectra of the nanocomposites
      which show marked size-dependence. The composites manifest strong absorption in
      the UV region, strong luminescence in the near UV region, and a moderate
      luminescence in the visible region.

PMID- 29019339
TI  - Facile synthesis of graphitic C3N4 nanoporous-tube with high enhancement of
      visible-light photocatalytic activity.
AB  - A simple and convenient method was used to synthesize a graphitic carbon nitride
      (g-C3N4) nanoporous-tube by using SiO2 nanoparticles as pore formers. The
      structure of the g-C3N4 nanoporous-tube was characterized by the SEM and TEM
      images. Taking photodegradation of RhB as an example, the photocatalytic activity
      of the as-prepared g-C3N4 nanoporous-tube was investigated. It can photodegrade
      90% RhB in 40 min under visible-light irradiation and obtain a k value of 0.04491
      min-1, which is 8.16 times that of bulk g-C3N4, 3.09 times that of tubular g-C3N4
      and 1.48 times that of tubular g-C3N4-SiO2. The significant enhancement in
      photocatalytic efficiency is due to the edge effect of the pores and the special
      structure of the tubes. In addition, the possible mechanism of photocatalytic
      degradation of RhB was also proposed based on the trapping experiment of active
      species, which indicated that the superoxide radicals ([Formula: see text]) and
      the holes (h +) were the main reactive species in this photocatalyst. This work
      may open up a new idea of innovation in g-C3N4 structure and inspire its follow
      up study.

PMID- 29019340
TI  - The influence of the dimensionality of the system on the realization of
      unconventional Fulde-Ferrell-Larkin-Ovchinnikov pairing in ultra-cold Fermi
      gases.
AB  - The recent development of experimental techniques in ultracold atomic Fermi gases
      is extremely helpful in the progress of the realization of the unconventional
      Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) superfluid phase in quasi-one dimensional
      systems (Liao et al 2010 Nature 467 567). Due to a Fermi surface nesting, which
      is enhanced in 1D, the low-dimensional systems are particularly good candidates
      to find the FFLO phase stable. We investigate the influence of a dimensional
      crossover (from one dimension (1D) to two dimensions (2D) or three dimensions
      (3D)) on the stability of the FFLO state in the spin-imbalanced attractive
      Hubbard model.

PMID- 29019341
TI  - Controllable synthesis of a novel magnetic core-shell nanoparticle for dual-modal
      imaging and pH-responsive drug delivery.
AB  - In this study, novel magnetic core-shell nanoparticles Fe3O4@La-BTC/GO have been
      synthesized by the layer-by-layer self-assembly (LBL) method and further modified
      by attachment of amino-modified PEG chains. The nanoparticles were thoroughly
      characterized by x-ray diffraction, FTIR, scanning electron microscopy and
      transmission electron microscopy. The core-shell structure was shown to be
      controlled by the LBL method. The drug loading of doxorubicin (DOX) within the
      Fe3O4@La-BTC/GO-PEG nanoparticles with different numbers of deposited layers was
      investigated. It was found that DOX loading increased with increasing number of
      metal organic framework coating layers, indicating that the drug loading can be
      controlled through the controllable LBL method. Cytotoxicity assays indicated
      that the Fe3O4@La-BTC/GO-PEG nanoparticles were biocompatible. The DOX was
      released rapidly at pH 3.8 and pH 5.8, but at pH 7.4 the rate and extent of
      release was greatly attenuated. The nanoparticles therefore demonstrate an
      excellent pH-triggered drug release. In addition, the particles could be tracked
      by magnetic resonance imaging (MRI) and fluorescence optical imaging (FOI). A
      clear dose-dependent contrast enhancement in T 2-weighted MR images and
      fluorescence images indicate the potential of these nanoparticles as dual-mode
      MRI/FOI contrast agents.

PMID- 29019342
TI  - The impact of a gamified world on medical education.

PMID- 29019343
TI  - The association between dietary inflammatory properties and bone mineral density
      and risk of fracture in US adults.
AB  - BACKGROUND/OBJECTIVES: To examine the associations of dietary inflammatory index
      (DII) with bone mineral density (BMD) and fracture risk in adult
      Americans.Subjects/Method:The United States National Health and Nutrition
      Examination Survey participants during 2005-2010 were included if they had
      measured data on dietary intake and BMD. DII scores were calculated from
      estimated micro- and macronutrients from a single 24-h dietary recall. BMD was
      measured using dual-energy X-ray absorptiometry densitometers. Risk of fractures
      was obtained from participant self-report (ever) based on doctor information.
      Analyze of covariance and chi2-tests were employed, while accounting for the
      complex survey design. RESULTS: A total of 18 318 participants were included,
      with 51.3% (9397) being men. Age, sex, race, physical activity, smoking, C
      reactive protein and body mass index-adjusted mean BMD (g/cm2) in different
      bodily sites significantly decreased across increasing quarters of the DII (all
      P<0.001). After further adjustment for calcium intake, the trend in BMD across
      DII quarters remained significant for total femur, femoral neck, trochanter and
      intertrochanter BMD (all P<0.001). Across increasing quarters of the DII, the
      proportion of fractures ranged from 1.1 to 1.5% for hip fracture (P=0.02), from
      7.9 to 10.5% for wrist fracture (P<0.001) and from 2.2 to 2.7% for spine fracture
      (P=0.002. Prevalent wrist fractures significantly differed across DII quarters
      (P<0.0001), driven by high prevalence in the top quarter, while hip and spine
      fractures' prevalence did not vary significantly. CONCLUSIONS: The current study
      provides evidence suggesting a potential adverse effect of pro-inflammatory diet
      on bone health; which may have implications for dietary approaches for those with
      history of abnormal bone health complications.

PMID- 29019347
TI  - Pituitary gland: Gamma Knife for Cushing disease - time for a reappraisal?

PMID- 29019345
TI  - Suspect screening of maternal serum to identify new environmental chemical
      biomonitoring targets using liquid chromatography-quadrupole time-of-flight mass
      spectrometry.
AB  - The use and advantages of high-resolution mass spectrometry (MS) as a discovery
      tool for environmental chemical monitoring has been demonstrated for
      environmental samples but not for biological samples. We developed a method using
      liquid chromatography-quadrupole time-of-flight MS (LC-QTOF/MS) for discovery of
      previously unmeasured environmental chemicals in human serum. Using non-targeted
      data acquisition (full scan MS analysis) we were able to screen for environmental
      organic acids (EOAs) in 20 serum samples from second trimester pregnant women. We
      define EOAs as environmental organic compounds with at least one dissociable
      proton which are utilized in commerce. EOAs include environmental phenols,
      phthalate metabolites, perfluorinated compounds, phenolic metabolites of
      polybrominated diphenyl ethers and polychlorinated biphenyls, and acidic
      pesticides and/or predicted acidic pesticide metabolites. Our validated method
      used solid phase extraction, reversed-phase chromatography in a C18 column with
      gradient elution, electrospray ionization in negative polarity and automated
      tandem MS (MS/MS) data acquisition to maximize true positive rates. We identified
      "suspect EOAs" using Agilent MassHunter Qualitative Analysis software, to match
      chemical formulas generated from each sample run with molecular formulas in our
      unique database of 693 EOAs assembled from multiple environmental literature
      sources. We found potential matches for 282 (41%) of the EOAs in our database.
      Sixty-five of these suspect EOAs were detected in at least 75% of the samples;
      only 19 of these compounds are currently biomonitored in National Health and
      Nutrition Examination Survey. We confirmed two of three suspect EOAs by LC
      QTOF/MS using a targeted method developed through LC-MS/MS, reporting the first
      confirmation of benzophenone-1 and bisphenol S in pregnant women's sera. Our
      suspect screening workflow provides an approach to comprehensively scan
      environmental chemical exposures in humans. This can provide a better source of
      exposure information to help improve exposure and risk evaluation of industrial
      chemicals.

PMID- 29019346
TI  - Occupational exposure to pesticides: development of a job-exposure matrix for use
      in population-based studies (PESTIPOP).
AB  - Occupational exposure to pesticides concerns a wide population of workers not
      only in agriculture. The reliability of self-reported information on pesticide
      use is questionable because of the diversity of use. The PESTIPOP job-exposure
      matrix has been designed to assess pesticide occupational exposure in the general
      population. The matrix is composed of two axes: the first axis corresponding to
      jobs (combinations of occupations and industries) and the second one to pesticide
      exposure. The estimated exposure metric is the probability of exposure coupled
      with a reliability assessment (low, medium or high). These metrics were defined
      by combining different sources: (1) an a priori expert assessment (Agricultural
      industry experts); (2) data from a multicenter case-control study on brain tumors
      in the general population (occupational history, specific questionnaires); and
      (3) an a posteriori expert assessment based on the data of a case-control study.
      So far, 2559 jobs have been identified and 209 (8%) were found to be exposed to
      pesticides. Jobs with agricultural exposure had a higher exposure probability
      than jobs with non-agricultural exposure (wood preservation, park maintenance,
      pest control). Indirect exposure was more frequent than direct exposure. The
      PESTIPOP matrix will be transcoded into international classifications for use in
      epidemiological studies.

PMID- 29019348
TI  - Paediatric endocrinology: Can niacin supplementation protect against congenital
      malformations?

PMID- 29019349
TI  - Do workers' health surveillance examinations fulfill their occupational
      preventive objective? Analysis of the medical practice of occupational physicians
      in Catalonia, Spain.
AB  - OBJECTIVES: Although routine workers' health examinations are extensively
      performed worldwide with important resource allocation, few studies have analyzed
      their quality. The objective of this study has been to analyze the medical
      practice of workers' health examinations in Catalonia (Spain) in terms of its
      occupational preventive aim. MATERIAL AND METHODS: A cross-sectional study was
      carried out by means of an online survey addressed to occupational physicians who
      were members of the Catalan Society of Safety and Occupational Medicine. The
      questionnaire included factual questions on how they performed health
      examinations in their usual practice. The bivariate analysis of the answers was
      performed by type of occupational health service (external/internal). RESULTS:
      The response rate was 57.9% (N = 168), representing 40.3% of the reference
      population. A high percentage of occupational physicians had important
      limitations in their current medical practice, including availability of clinical
      and exposure information, job-specificity of tests, and early detection and
      appropriate management of suspected occupational diseases. The situation in
      external occupational health services - that covered the great majority of
      Catalan employees - was worse remarkably in regard to knowledge of occupational
      and nonoccupational sickness absence data, participation in the investigation of
      occupational injuries and diseases, and accessibility for workers to the
      occupational health service. CONCLUSIONS: This study raises serious concerns
      about the occupational preventive usefulness of these health examinations, and
      subsequently about our health surveillance system, based primarily on them.
      Professionals alongside health and safety institutions and stakeholders should
      promote the rationalization of this system, following the technical criteria of
      need, relevance, scientific validity and effectiveness, whilst ensuring that its
      ultimate goal of improving the health and safety of workers in relation to work
      is fulfilled. Other countries with similar surveillance systems might be
      encouraged by our results to assess how their practices fit the intended purpose.
      Int J Occup Med Environ Health 2017;30(6):823-848.

PMID- 29019350
TI  - Influenece of the CPRmeter on angular position of elbows and generated forces
      during cardiopulmonary resuscitation.
AB  - OBJECTIVES: It is commonly known that ergonomics in emergency medical services
      (EMS) is very important. Emergency medical services workers are exposed to
      different conditions and they should perform a variety of tasks. MATERIAL AND
      METHODS: The aim of the work has been to analyze the angular position of elbows
      and forces generated by the upper limbs during cardiopulmonary resuscitation with
      and without the CPRmeter based on feedback technology. Ten male paramedics and 10
      male non-paramedics, in a kneeling position, performed cardiopulmonary
      resuscitation (CPR) on an Ambu Megacode manikin placed on the ground.
      Measurements were taken after 1 min and 4 min following the beginning of the
      trial. The angular position of the elbows was evaluated with a BTS Smart DX 7000
      motion capture system. Kistler platforms 9286BA were used for measuring forces.
      RESULTS: In the paramedic group, one statistically significant difference was
      observed in the mean difference between maximal and minimal right elbow angle in
      the 1st min without the device vs. the mean difference in the 4th min without the
      device. In the paramedic group, a 25% force decrease was observed after 4 min of
      resuscitation in trials without the CPRmeter in comparison to the 1st min. In
      trials with the CPRmeter, the force parameters were similar in the 1st and 4th
      min and more stable. No statistically significant differences were noticed in the
      control group. CONCLUSIONS: The CPRmeter has influence on the magnitude of the
      forces applied by the upper limbs and on the optimization of the rescuer effort
      during cardiopulmonary resuscitation. The CPRmeter had no influence on the
      position of the upper part of the kinematic chain. Int J Occup Med Environ Health
      2017;30(6):909-916.

PMID- 29019351
TI  - Hot News: Exosomes as New Players in HIV Pathogenesis - New Data from the IAS
      2017.
AB  - Exosomes are nanovesicles that can be released into the extracellular medium by
      different cell types and are considered an important system of intercellular
      communication. In some instances, on secretion, exosomes break down and release
      their content into the extracellular space. Alternatively, intact exosomes can
      interact with other cells and discharge their content directly into the target
      cell cytoplasm. Exosomes are rich in endosome-associated proteins (i.e., the
      tetraspanin family) but also carry different molecules in their lumen including
      proteins, RNAs (i.e., microRNAs), and pathogenderived cargo. Indeed, the
      different biological functions of exosomes might depend on their cargo
      components. Several recent publications have identified exosomes as new players
      in the pathogenesis of HIV infection. This is an emerging field of growing
      interest that deserved a satellite symposium at the 9th IAS Conference held in
      Paris in July 2017, sponsored by the International Society for Extracellular
      Vesicles (EVs). Although the role of exosomes in HIV infection is not yet
      clarified, accumulating data suggest that exosomes may act at different levels of
      HIV pathogenesis by modulating immune responses, infectivity, or even by
      activating the latent viral reservoir. However, there are still methodological
      limitations that need to be resolved to advance our understanding of the role of
      exosomes in HIV infection. One particular limitation is to define an accurate and
      reproducible procedure for their isolation. A new strategy to separate exosomes
      from HIV-1-infected cells was proposed at this symposium. Martin-Jaular and
      colleagues (Institut Curie, France) used velocity centrifugation gradients and
      antibody labeling of specific endosome-associated protein markers (i.e., CD45+
      and AChE+) to isolate pure exosomes from complex preparations of EVs. Separately,
      Arakelyan and colleagues (NIH, USA) used flow cytometry coupled with magnetic
      nanoparticles to characterize the antigenic composition of EVs and demonstrate
      that EVs carrying HIV envelope proteins facilitated HIV infection. This is an
      interesting observation that could lead to the discovery of new antiviral drugs
      targeting EVs that contain HIV-Env. Exosomes might also have an effect on the
      viral reservoir. Kashanchi et al. (George Mason University, USA) presented
      interesting results demonstrating how exosomes from HIV-uninfected cells could
      reactivate latent HIV-1 in infected cells. They proposed a mechanism in which
      exosomes might increase RNA polymerase II loading onto the HIV-1 promoter in the
      infected cells, thereby facilitating transcription and leading to an increase of
      cellular activation. These presentations represent just a small piece of the
      growing body of research focused on the role of exosomes in HIV infection. We
      stand at the beginning of a new source of knowledge of HIV pathogenesis that may
      provide novel strategies to control HIV infectivity, regulate HIV-reactive immune
      responses, and act against the HIV reservoir. The impact of exosomes on HIV
      infection at all these levels should be considered in ongoing and future
      approaches to achieve HIV remission and cure.

PMID- 29019352
TI  - Hot News: Gene Therapy with CRISPR/Cas9 Coming to Age for HIV Cure.
AB  - The huge success of current antiretroviral therapy is mediated by a triple
      effect: (i) Halting progression to AIDS in infected persons; (ii) reducing the
      risk of transmission to contacts (treatment as prevention); and (iii) minimizing
      the risk of HIV acquisition treating uninfected persons at risk (pre-exposure
      prophylaxis). However, UNAIDS has estimated that only 70% of infected people
      globally are diagnosed, only 53% are treated, and overall 44% have undetectable
      viral load, which is the necessary request for ensuring any antiretroviral
      benefit. Thus, with 37 million people currently living with HIV worldwide and
      more than 2 million new infections per year, the prospects for global HIV
      eradication are far on the horizon. Over the past couple of years, rapid
      development has been seen for technologies enabling modification of gene
      expression, either by direct inhibition by RNA interference (RNAi) or by genomic
      modification at DNA level. In particular, genome-editing endonucleases have
      significantly improved our ability to make precise changes in the DNA of
      eukaryotic cells. Notably, firstgeneration genome-editing technologies (i.e.,
      ZFNs and TALENs) have been replaced by clustered regularly interspaced short
      palindromic repeats (CRISPR/Cas9), which work with a short guide RNA (gRNA) to
      hybridize to a target DNA site and recruit the Cas9 endonuclease. Once integrated
      into the host genome, HIV gene expression is regulated by the LTR promoter.
      Hypothetically, gene editing of the HIV promoter might have the potential to
      deactivate viral transcription by the introduction of mutations or fragment
      excision. HIV gene therapy progressed very slowly until recent breakthroughs in
      gene-editing methods using CRISPR/Cas9 (Liao et al. Nat Commun 2015;6:6413).
      Using a shorter version of the Cas9 endonuclease ensembled into an adenoviral
      vector, critical segments of thAQ!e viral DNA genome spanning between the LTR and
      gag regions were successfully removed in HIV transgenic mice. Excision was
      confirmed in all examined tissues as well as in circulating lymphocytes and
      resulted in a drastic reduction of HIV-RNA (Kaminski et al. Gene Ther 2016;23:690
      5). Moreover, using latently infected CD4+ T lymphocytes from HIV-infected
      persons, lentiviral-delivered CRISPR/Cas9 precisely removed the entire HIV genome
      spanning between the 50 and 30 LTRs of integrated HIV proviral DNA (Kaminski et
      al., Sci Rep 2016;6:22555), providing a proof of concept of the high potential of
      genome-editing technologies. Before moving to the clinic, the CRISPR/Cas9
      technology must solve several major issues in the HIV scenario. First, generation
      of resistance is a major concern. Mutations may occur surrounding the targeted
      site and result in the selection of strains that are no longer recognized nor
      cleaved by CRISPR (Badia et al. Curr Opin Virol 2017;24:46-54). The efficacy of
      the anti-HIV CRISPR/Cas9 strategy is highly dependent on the gRNA sequence, yet
      some mutant viral strains show poor or no cleavage at all. Higher CRISPR/Cas9
      pressure could delay but not eliminate viral replication when using a combination
      of distinct gRNAs targeting distinct HIV proviral genes. In this case, although
      the reading frame may remain unaltered, an accumulation of insertions and/or
      deletions may occur in the target sequence, rendering new viral strains
      insensitive to CRISPR/Cas9 cleavage. Finally, double-strand breaks resulting from
      CRISPR/Cas9 activity and subsequent cellular non-homologous end joining machinery
      may introduce mutations in sequences that are no longer recognized by the gRNA,
      and therefore not susceptible to Cas9 cleavage. A second consideration is a need
      for developing safe and effective mechanisms of delivery. Adenoviral vectors have
      long been studied in gene therapy and represent an ideal viral vector for
      transduction at different tissues. However, the packaging size of adenoviral
      vectors is a limiting factor, especially for CRIPSR/Cas9. Third, HIV has a genome
      of about 10 kb while a gRNA generally only targets 20 bp of the DNA molecule,
      which means that there are thousands available targeting sites for the provirus
      in latently infected cells. To date, there is no platform established solely for
      gRNA candidate evaluation in HIV provirus eradication. A final consideration is
      an access to all tissues and cells potentially harboring the HIV provirus,
      including reservoirs as the central nervous system. In this regard, efforts are
      being focused in the development of Cas9/gRNA nanoparticle formulations. To
      overcome these problems, a group in Florida recently developed human transgenic
      cells that may be used for gene-editing studies and as platform for high
      throughput screen of HIV provirus disrupters (Huang et al. Sci Rep 2017;7:5955).
      Of note, Cas9 protein instead of a Cas9 plasmid was used. Compared to a plasmid
      introduction, Cas9 protein agents could be easily quantitatively applied and
      standardized, mimicking better real clinic scenarios. In summary, RNAi-based
      technologies have widely dominated gene therapy research during the past decade,
      with overall slow progress. However, the advent of new gene-editing technologies,
      and especially the CRISPR/Cas9 system, has revolutionized the field. In the HIV
      context, CRISPR/Cas9 applications might go further than those of RNAi, for
      example, enabling excision of segments of integrated proviral DNA from latently
      infected cells and allowing complete provirus elimination, or it may be used to
      reverse HIV latency. Although important challenges still need to be overcome, a
      promising pathway to HIV cure seems to have been found.

PMID- 29019353
TI  - Hot News: Ready for HIV Dual Therapy? - New Data from International HIV/AIDS
      Society 2017.
AB  - The introduction of combination antiretroviral therapy (ART) in the 1990s has
      fundamentally transformed the landscape of HIV medicine, greatly improved disease
      morbidity and mortality, and reduced transmission rates across all demographic
      groups. Central to this success was the idea that to achieve best disease
      outcomes and minimize the development of drug resistance, at least three
      antiretroviral agents should be used for HIV treatment. This therapeutic strategy
      is a core tenet of HIV medicine, backed by incontrovertible scientific evidence,
      and made easy to deploy by the high compliance levels with once-daily
      coformulations, which have generally been well tolerated. However, there has been
      increasing support for a paradigm shift toward dual therapy in recent years,
      particularly during the maintenance therapy phase of treatment. This concept
      advocates that once virologic suppression has been achieved with at least three
      antiretroviral drugs during the treatment initiation phase, a switch to a two
      drug regimen should be possible. The results of Phase III of the SWORD trials
      (Llibre et al., Abstract 44LB) and LAMIDOL trial (Joly et al., Abstract 458)
      presented at the 2017. Conference on Retroviruses and Opportunistic Infections
      earlier this year seemed to lend support this hypothesis. More new evidence was
      recently presented at the 2107 International HIV/AIDS Society (IAS) meeting in
      Paris that adds to the growing body of evidence in favor of a two-drug regimen
      approach in maintenance therapy. The LATTE-2 study (Eron et al., Abstract 5628)
      was of major interest because of the exciting new therapeutic options that long
      acting injectable antiretroviral agents may bring in the near future. However,
      more than that, the findings of comparable response between a traditional three
      drug oral regimen and a novel injectable two-drug regimen at 96 weeks were quite
      noteworthy. In this Phase II, multicenter open-label study of 286 HIV-infected
      ARTnaive patients, once-daily oral cabotegravir/abacavir/lamivudine achieved
      virologic suppression in 84% of study participants. In comparison, 87% in the
      injectable cabotegravir/rilpivirine once every 4-weekly group and 94% in
      injectable cabotegravir/rilpivirine once every 8-weekly group remained suppressed
      at 96 weeks. Crucially, no drug resistance mutations were seen in study
      participants who remained on their regimen. While the idea of a two-drug regimen
      has been entertained for maintenance therapy, there may be little willingness to
      push this further into the area of antiretroviral treatment initiation, for the
      justifiable concerns that exist around the emergence of drug resistance. Despite
      this, new data presented at the IAS 2017 showed that the idea is not without
      merit. In a proof of concept, the ACTG A5353 single-arm pilot study of 120
      treatment naive HIV-infected participants with high viral load (VL >=1000 and
      >500,000 copies/mL), showed that once-daily dolutegravir/lamivudine had virologic
      efficacy of 90% at 24 weeks, with 96% of the as-treated study population
      achieving VL >50 copies/mL (Taiwo et al., Abstract MOAB0107LB). The regimen was
      well tolerated, with no reported drug resistance mutations while on treatment.
      There are many real-world advantages to a two-drug regimen approach, among them
      lower costs (crucial in resource-limited settings where affordability may be a
      limiting factor), fewer adverse effects or drug toxicities, and possibly improved
      compliance. These are all important considerations, given that improved mortality
      now means patients are going to stay on ART treatment for much longer than
      previously seen. But how the two-drug regimen approach will hold up against
      firmly held norms and tradition is far from clear, and it is almost certain that
      the understandable nervousness that surrounds this idea will continue to last.
      Until the case for the two-drug regimen approach is made more convincingly in
      ongoing and future trials, the "three or more" rule will reign, not only as the
      orthodoxy but also as the cornerstone of good clinical practice.

PMID- 29019355
TI  - Improvement of thermal stability and photoluminescence in Sr0.8Ca0.2Al2Si2O8:Eu2+
      by the substitution of Si-Na # Al-Sr and Ca # Sr for structural modifications.
AB  - Blue emitting phosphor is urgently needed in commercial application of white
      light emitting diodes for the reason that the existing ones lack proper emission
      and have poor thermal stability. Herein, we report two methods for
      Sr0.8Ca0.2Al2Si2O8:Eu2+ phosphors that were performed to optimize the
      luminescence properties and thermal stability based on structural reconstruction.
      One is partial substitution of Al3+-Sr2+ by Si4+-Na+ forming Sr0.77-xNaxCa0.2Al2
      xSi2+xO8:0.03Eu2+ (x = 0-0.7); the other is altering the proportion of Ca2+ and
      Sr2+, forming Sr0.97-yCayAl2Si2O8:0.03Eu2+ (y = 0-0.97) solid solution. The
      phosphor's structural evolution, variation of the Eu2+ local environment,
      luminescence and thermal quenching were explored in detail. As a result, for
      Sr0.77-xNaxCa0.2Al2-xSi2+xO8:0.03Eu2+ (x = 0-0.7) series, (Al/Si)O4 tetrahedrons
      are enlarged and Eu-O polyhedrons are compressed; the emission gets red-shifted
      from 418 nm to 428 nm under 350 nm excitation; the thermostability of Sr0.97
      yCayAl2Si2O8:0.03Eu2+ is improved with the incorporation of Si4+-Na+ pair. For
      Sr0.97-yCayAl2Si2O8:0.03Eu2+ (y = 0-0.97) series, the emission peak shows a large
      shift from 420 nm to 440 nm, which is attributed to a comprehensive result of
      nephelauxetic effect and crystal field splitting. Furthermore, thermal stability
      is improved by the coexistence of Ca2+ and Sr2+. White light emitting diodes
      fabricated by combining the as-prepared phosphor with commercial phosphors
      exhibit an excellent color rendering index Ra of 90.1 and a temperature of 4459 K
      with CIE coordinates of (0.357, 0.356). These results indicate that the as
      developed composition series are promising for commercial application.

PMID- 29019356
TI  - Pyrolysis of covalent organic frameworks: a general strategy for template
      converting conventional skeletons into conducting microporous carbons for high
      performance energy storage.
AB  - Here we describe a general strategy based on template pyrolysis for converting
      conventional covalent organic frameworks into high-performance carbons, which
      combines conductivity, microporosity and heteroatom density, thus casting a
      distinct contrast to those obtained upon direct pyrolysis. The carbons serve as
      electrodes and exhibit exceptional performance in energy storage.

PMID- 29019357
TI  - Construction of biological hybrid microcapsules with defined permeability towards
      programmed release of biomacromolecules.
AB  - An effective method to modulate the permeability of microcapsules on demand based
      on a "self-sacrificing" strategy was demonstrated, which then realized a
      programmed release of the corresponding loaded biomacromolecules.

PMID- 29019358
TI  - Protonation and electrochemical reduction of rhodium- and iridium-dinitrogen
      complexes in organic solution.
AB  - Protonation and reduction of pincer-ligated Rh- and Ir-N2 complexes have been
      studied by NMR spectroscopy and cyclic voltammetry to assess the capability of
      these complexes to activate or reduce N2. Protonation, which is a prerequisite to
      electrochemical reduction, results in a cationic metal-hydride that loses N2
      under an atmosphere of Ar. Reduction of the metal-hydride results in fast
      disproportionation of an unobserved transient Ir2+ species. These studies suggest
      that the regioselectivity of initial protonation is a strong determinant for the
      ability of a system to facilitate the reduction of N2.

PMID- 29019359
TI  - Unprecedented magnetic behaviour in lanthanide-based ionic liquids.
AB  - Ionic liquids containing lanthanide halide anions give the opportunity to
      investigate magnetic behaviour in non-ordered systems. Reported herein is the
      synthesis and characterization of ionic liquids containing a series of lanthanide
      halide anions, with the resulting materials displaying unusual behaviour below 50
      K. Specifically, the ionic liquid structural glass formation appears to drive
      magnetic behaviour due to cluster formation of the anions during rapid cooling.
      This system presents a possible probe to study the dynamics of glass forming
      materials.

PMID- 29019360
TI  - Mitigating the effects of high fat diet on the brain and behavior with berry
      supplementation.
AB  - Research on the potential of berries to modulate the effects of high fat diets on
      the brain and behavior is a relatively small and growing field. This review
      provides an overview of current findings from animal studies assessing the impact
      of high fat diets supplemented with blueberries, blackberries, grapes and
      jaboticaba berries on cognitive performance and neuroprotection. High fat diets
      are demonstrated to increase brain markers of oxidative stress and inflammation
      and result in other neural alterations that can contribute to impairments in
      learning and memory. Berries are rich in bioactive polyphenols and show promise
      for mitigating the effects of high fat diet. Challenges to systematic research
      include variability in diet composition and regimens, limitations of
      predominantly male animal models, and other factors. Links between peripheral
      inflammation and CNS dysfunction have implications for the understanding of
      underlying mechanisms and directions for future research.

PMID- 29019361
TI  - Copper(i)-catalysed asymmetric allylic reductions with hydrosilanes.
AB  - A copper(i)-catalysed asymmetric allylic reduction enables a regio- and
      stereoselective transfer of a hydride nucleophile in an SN2'-fashion onto allylic
      bromides. This transformation represents a conceptually orthogonal approach to
      allylic substitution reactions with carbon nucleophiles. A copper(i) complex
      based upon a chiral N-heterocyclic carbene (NHC) ligand allows for
      stereoselectivity reaching 99% ee. The catalyst enables a stereoconvergent
      reaction irrespective of the double bond configuration of the starting materials.

PMID- 29019362
TI  - An interesting 1,4,2,5-dioxadiazine-furazan system: structural modification by
      incorporating versatile functionalities.
AB  - Herein, the 1,4,2,5-dioxadiazine ring is combined with two furazan rings.
      Interestingly, the structure of the 1,4,2,5-dioxadiazine-furazan system can be
      modified by incorporating versatile functionalities. The N-trinitroethylamino
      functionalization derivatives and energetic salts based on 3,6-bis(4-amino-1,2,5
      oxadiazol-3-yl)-1,4,2,5-dioxadiazine are investigated. Derivatives of these
      functionalities are synthesized and fully characterized via multinuclear NMR
      spectroscopy, IR spectroscopy, and elemental analysis. The structures of
      compounds 1-7 are further confirmed by single-crystal X-ray diffraction.
      Compounds 1-12 have moderate thermal stabilities (143-177  degrees C, except 2
      (114  degrees C), and 3 (88  degrees C)) and exhibit acceptable sensitivities (IS
      3.52-16.3 J and FS 100-240 N). Based on the measured densities (1.73-1.95 g cm-3)
      and heats of formation (573.5-2065.4 kJ mol-1), the detonation velocities (D 8519
      9563 m s-1) and pressures (P 29.3-43.3 GPa) are calculated. Among them, the
      trinitroethylamino derivative 1 and ammonium salt of 3,6-bis(4-nitroamino-1,2,5
      oxadiazol-3-yl)-1,4,2,5-dioxadiazine 5 show a layered assembly of the 1,4,2,5
      dioxadiazine-furazan system. These two compounds show good thermal stabilities
      (1, 154  degrees C and 5, 177  degrees C) and relatively low sensitivities (1,
      16.3 J and 5, 13.4 J). These properties indicate that the layer assembly
      structure is helpful to improve the thermal stabilities and result in low
      sensitivities for the corresponding compounds.

PMID- 29019354
TI  - Iron-sulfur cluster biosynthesis and trafficking - impact on human disease
      conditions.
AB  - Iron-sulfur clusters (Fe-S) are one of the most ancient, ubiquitous and versatile
      classes of metal cofactors found in nature. Proteins that contain Fe-S clusters
      constitute one of the largest families of proteins, with varied functions that
      include electron transport, regulation of gene expression, substrate binding and
      activation, radical generation, and, more recently discovered, DNA repair.
      Research during the past two decades has shown that mitochondria are central to
      the biogenesis of Fe-S clusters in eukaryotic cells via a conserved cluster
      assembly machinery (ISC assembly machinery) that also controls the synthesis of
      Fe-S clusters of cytosolic and nuclear proteins. Several key steps for synthesis
      and trafficking have been determined for mitochondrial Fe-S clusters, as well as
      the cytosol (CIA - cytosolic iron-sulfur protein assembly), but detailed
      mechanisms of cluster biosynthesis, transport, and exchange are not well
      established. Genetic mutations and the instability of certain steps in the
      biosynthesis and maturation of mitochondrial, cytosolic and nuclear Fe-S cluster
      proteins affects overall cellular iron homeostasis and can lead to severe
      metabolic, systemic, neurological and hematological diseases, often resulting in
      fatality. In this review we briefly summarize the current molecular understanding
      of both mitochondrial ISC and CIA assembly machineries, and present a
      comprehensive overview of various associated inborn human disease states.

PMID- 29019363
TI  - Near-infrared light-mediated LA-UCNPs@SiO2-C/HA@mSiO2-DOX@NB nanocomposite for
      chemotherapy/PDT/PTT and imaging.
AB  - Currently, incorporating multiple therapeutic functions into one nanoplatform is
      attracting increasing attention for the development of efficient anticancer
      agents. Here, a novel core-shell-shell nanoparticle, which was synthesized to
      integrate imaging and photodynamic therapy (PDT) with photothermal therapy (PTT)
      and chemotherapy for enhanced antitumor efficiency, consists of upconversion (UC)
      core (NaYF4:Yb,Tm@NaYF4), Hypocrellin A (HA)/carbon dot (C-Dot) embodied silica
      sandwich shell, and mesoporous silica outer-shell. A photolabile o-nitrobenzyl
      derivative linker (NB linker) was prepared as the sensitive "gate" to encapsulate
      an anticancer drug (doxorubicin hydrochloride, DOX) in the mesopore. Upon 980 nm
      light irradiation, the UV-emission can induce the bond breaking of the NB linker
      as well as drug release. The visible emission can stimulate HA to generate
      singlet oxygen species (ROS); moreover the incorporated C-Dots also can absorb
      this light to evolve heat. In view of the excess expression of the lactobionic
      acid (LA) receptor on tumor cells, LA were grafted outside the nanocomposites to
      insure their specific targeting. The synergistic effect of NIR-triggered
      chemotherapy with PTT and PDT would be expected to reveal the enhanced
      cytotoxicity to cancer cells. And the novel UC and C/HA fluorescence also makes
      the nanocomposites a potential candidate for the imaging-guided multi-therapy.

PMID- 29019364
TI  - A serving of blueberry (V. corymbosum) acutely improves peripheral arterial
      dysfunction in young smokers and non-smokers: two randomized, controlled,
      crossover pilot studies.
AB  - Several studies have documented the important role of polyphenol-rich foods in
      the modulation of vascular remodelling and function. This study aimed to evaluate
      the capacity of a single portion of blueberry (V. corymbosum) to acutely improve
      peripheral arterial dysfunction in a group of young volunteers. Twenty-four
      healthy males (12 non-smokers and 12 smokers) were recruited for two different
      randomized, controlled, crossover pilot acute studies. In the first study, non
      smokers were exposed to a control treatment (C; 300 mL of water with sugar) and a
      blueberry treatment (BB; 300 g of blueberry). In the second study, smokers
      underwent 3 different protocols: (1) - smoking treatment (S); (2) - control
      treatment (CS; 300 mL of water with sugar + smoking); (3) - blueberry treatment
      (BS; 300 g of blueberry + smoking). Each treatment (1 day long) was separated by
      a one week washout period. Blood pressure, peripheral arterial function (reactive
      hyperemia index, RHI, a marker of endothelial function) and arterial stiffness
      (digital augmentation index, dAix and dAix normalized by considering a heart rate
      of 75 bpm, dAix@75) were measured before and after each treatment. In the first
      study, the consumption of blueberry and control treatment acutely increased
      peripheral arterial function in the group of non-smokers. The improvement in RHI
      was higher and significantly different after blueberry treatment compared to the
      control treatment (54.8 +/- 8.4% BB vs. 28.2 +/- 8.3% C; p = 0.01). No effects
      were observed for markers of arterial stiffness, blood pressure and heart rate.
      Acute cigarette smoke significantly increased blood pressure and heart rate,
      while no significant effect was registered in peripheral arterial function and
      stiffness. The intake of blueberry and control treatment before a cigarette did
      not counteract the increase in blood pressure and heart rate, while it
      significantly improved peripheral arterial function. In particular, a significant
      increase was observed following BS (35.2 +/- 7.5% RHI; p = 0.02) and CS
      treatments (34.6 +/- 11.9% RHI; p = 0.02) when compared to only smoking
      treatment. No difference between BS and CS was detected. In conclusion, the
      intake of blueberry and control treatments acutely improved peripheral arterial
      dysfunction both in smoker and in non-smoker subjects. Further studies should be
      performed to confirm the results obtained and reveal the potential mechanisms of
      blueberry in the improvement of endothelial function.

PMID- 29019365
TI  - Blueberry supplementation attenuates oxidative stress within monocytes and
      modulates immune cell levels in adults with metabolic syndrome: a randomized,
      double-blind, placebo-controlled trial.
AB  - BACKGROUND: Blueberries (BB) have been shown to improve insulin sensitivity and
      endothelial function in obese and pre-diabetic humans, and decrease oxidative
      stress and inflammation, and ameliorate cardio-renal damage in rodents. This
      indicates that blueberries have a systemic effect and are not limited to a
      particular organ system. In order for blueberries to exert beneficial effects on
      the whole body, the mechanism would logically have to operate through modulation
      of cellular humoral factors. OBJECTIVE: This study investigated the role of
      blueberries in modulating immune cell levels and attenuating circulatory and
      monocyte inflammation and oxidative stress in metabolic syndrome (MetS) subjects.
      DESIGN: A double-blind, randomized and placebo-controlled study was conducted in
      adults with MetS, in which they received a blueberry (22.5 g freeze-dried) or
      placebo smoothie twice daily for six weeks. Free radical production in the whole
      blood and monocytes, dendritic cell (DC) levels, expression of cytokines in
      monocytes and serum inflammatory markers were assessed pre- and post
      intervention. RESULTS: Baseline free radical levels in MetS subjects' samples
      were not different between groups. Treatment with blueberries markedly decreased
      superoxide and total reactive oxygen species (ROS) in whole blood and monocytes
      compared to the placebo (p <= 0.05). The baseline DC numbers in MetS subjects'
      samples in both groups were not different, however treatment with blueberries
      significantly increased myeloid DC (p <= 0.05) and had no effect on plasmacytoid
      cells. Blueberry treatment decreased monocyte gene expression of TNFalpha, IL-6,
      TLR4 and reduced serum GMCSF in MetS subjects when compared to the placebo
      treatment (p <= 0.05). CONCLUSIONS: The findings of the current study demonstrate
      that blueberries exert immunomodulatory effects and attenuate oxidative stress
      and inflammation in adults with MetS.

PMID- 29019366
TI  - Moderation of hyperuricemia in rats via consuming walnut protein hydrolysate diet
      and identification of new antihyperuricemic peptides.
AB  - In this study, walnut meal hydrolysates (WMH) and dephenolized walnut meal
      hydrolysates (DWMH) were found to effectively decrease the serum uric acid level
      and protect the renal function in potassium oxonate-induced hyperuricemic rats in
      vivo as well as inhibit xanthine oxidase in vitro. Two novel antihyperuricemic
      peptides including WPPKN (640.8 Da) and ADIYTE (710.7 Da) were purified from DWMH
      via Sephadex G-15 gel filtration and reverse-phase high-performance liquid
      chromatography and identified by LC-ESI-MS/MS. These peptides displayed high in
      vitro xanthine oxidase inhibition (XOI) activity with IC50 values of 17.75 +/-
      0.12 mg mL-1 (WPPKN) and 19.01 +/- 0.23 mg mL-1 (ADIYTE). Based on the results of
      molecular simulation, WPPKN entered into the hydrophobic channel and even
      obstructed the interaction between xanthine and xanthine oxidase (XO), while
      ADIYTE was positioned on the surface of the B-chain and blocked the entrance of
      the substrate to the hydrophobic channel. Therefore, the two peptides are
      partially responsible for the antihyperuricemic properties of DWMH.

PMID- 29019367
TI  - One-pot organometallic synthesis of alumina-embedded Pd nanoparticles.
AB  - Herein we report a one pot organometallic strategy to access alumina-embedded Pd
      nanoparticles. Unexpectedly, the decomposition of the organometallic complex
      tris(dibenzylideneacetone)dipalladium(0), Pd2(dba)3, by dihydrogen in the
      presence of aluminum isopropoxide, Al(iPrO)3, and without extra stabilizers, was
      found to be an efficient method to generate a Pd colloidal solution. Careful
      characterization studies revealed that the so-obtained Pd nanoparticles were
      stabilized by an aluminum isopropoxide tetramer and 1,5-diphenyl-pentan-3-one,
      which was produced after reduction of the dba ligand from the organometallic
      precursor. Moreover, calcination of the obtained nanomaterial in air at 773 K for
      2 h resulted in a nanocomposite material containing Pd nanoparticles embedded in
      Al2O3. This stabilization strategy opens new possibilities for the preparation of
      transition metal nanoparticles embedded in oxides.

PMID- 29019368
TI  - Quasielastic neutron scattering study of microscopic dynamics in polybutadiene
      reinforced with an unsaturated carboxylate.
AB  - We studied the dynamics of zinc diacrylate (ZDA) reinforced polybutadiene rubber
      (BR) (ZDA/BR) using the quasielastic neutron scattering technique to determine
      the effect of concentration of ZDA on polymer dynamics. First, we evaluated the
      temperature dependence of mean square displacements (<u2>) for ZDA/BR with
      different ZDA volume fractions. <u2> increased with temperature below 170 K, and
      we observed no significant ZDA volume fraction dependence. However, it increased
      more steeply above 170 K, and the value of <u2> was smaller for the samples with
      increasing ZDA fraction. To elucidate the origin of the decrease in <u2> with
      increasing ZDA content, dynamic scattering laws (S(Q,omega)) were analyzed. An
      increase in the elastic component, an increase in the mean relaxation time, and a
      broadening of distribution of relaxation time were observed with the increasing
      volume fraction of ZDA. In addition, the ZDA volume fraction dependence of the
      elastic component roughly corresponded to that of elastic modulus, indicating
      that the elastic component is related to its mechanical strength. Referring to
      the previously reported static structure of the present ZDA/BR system, a model
      for the heterogeneous BR dynamics was proposed. This model assumes the
      coexistence of immobile, mobile, and interfacial constrained mobile regions. It
      was found to be appropriate for the explanation of the observed dynamics. We
      proposed that a network-like structure of the BR having a high crosslinking
      density around ZDA aggregates is mainly responsible for the high elastic modulus
      of ZDA/BR.

PMID- 29019369
TI  - In situ generation of layered single- or double-hydroxide inorganic platelets
      (LSH and LDH) assisted by bola amphiphiles.
AB  - A novel preparation route for layered hydroxide based hybrid phases has been
      investigated combining the polyol route with the in situ generation of inorganic
      platelets, in the presence of an amphiphilic polymer as well as bola-amphiphiles.
      The polyol route consists of hydrolysis in an alcoholic medium containing acetate
      metal cations as precursor(s), to yield an LDH Zn2Al cation composition or LSH-Zn
      (layered single hydroxide). A bola amphiphile is described as hydrophobic polymer
      segment-telechelic-chains terminated by two anionic hydrophilic end groups, using
      volatile ammonium cations as counter ions. The impact of both process conditions
      as well as the chosen system with regard to the metal hydroxide framework on the
      morphology of the obtained hybrid phases is scrutinized by X-ray diffraction
      (XRD), small angle X-ray scattering (SAXS) and transmission electron microscopy
      (TEM), and compared to that of the corresponding physical mixture. For the ex
      situ approach, the diffusion of large cumbersome polymers or amphiphilic bolas
      between the inorganic platelets was found to be efficient, mostly driven by an
      anion exchange reaction between interleaved acetate anions and carboxylate
      functions of the molecular backbones, and keeping intact the inner sheet
      integrity through a topotactic process. In particular with LSH-Zn, a multi
      stratified assembly has been observed combining an acetate pristine structure and
      a partly bola diffused structure, leading to a biphasic structure, aggregated and
      intercalated. To the best of our knowledge, observation of LSH-Zn single
      platelets has never been reported, making the combined process polyol/in situ an
      interesting new route to reach exfoliation. Indeed, it leads to the generation of
      either LSH or LDH platelets of lateral size ranging from 10 up to 200 nm.
      However, the platelets were found to be porous; it is considered as a drawback
      for barrier properties. It is our belief that such porosity may open new insights
      in "tectonic" architecture by intertwining 2D and 1D-type fillers. Rather
      counterintuitively, the ex situ approach based on a topotactic exchange reaction
      matches the in situ templating reaction in many cases as a function of the
      dispersion state regardless of the polymer or bolas as well as the platelet
      cation composition.

PMID- 29019371
TI  - MicroRNA-590-5p regulates cell viability, apoptosis, migration and invasion of
      renal cell carcinoma cell lines through targeting ARHGAP24.
AB  - Renal cell carcinoma (RCC) is the leading cause of death in renal malignancies.
      MicroRNA-590-5p (miR-590-5p) is of great importance in the processes of many
      cancers regarding regulation of cancer cell invasion and proliferation. In our
      study, alternation of miR-590-5p expression in RCC cell lines through
      transfection with pre-miR-590-5p (up-regulation) or anti-miR-590-5p (down
      regulation) was performed. Apoptosis and viability of RCC cell lines were
      measured by flow cytometry and CCK-8 analysis, respectively. Cell invasion and
      migration were estimated by Transwell assay. The association of miR-590-5p with
      ARHGAP24 expression was evaluated using luciferase assays, real-time PCR and
      western blot assay. The expressions of apoptosis and migration-related protein
      were also measured by western blotting. We found that pre-miR-590-5p transfection
      in Caki-2 and 786-O cells showed significant increases in cell viability,
      invasion and migration, which were accompanied by decreased cell apoptosis, while
      anti-miR-590-5p transfection obviously inhibited the cell viability, migration
      and invasion of Caki-2 and 786-O cells as well as induced apoptosis, compared
      with the negative control group. Furthermore, bioinformatics combined with
      luciferase reporter assays indicated that ARHGAP24 is directly targeted by miR
      590-5p. ARHGAP24 overexpression in 786-O and Caki-2 cells phenocopied the effects
      of anti-miR-590-5p transfection along with enhanced expression of active Caspase
      3 and Bax/Bcl-2 ratio as well as decreased expression of MMP-2 and MMP-9. These
      findings suggested that miR-590-5p/ARHGAP24 seems to function as a potentially
      beneficial target for RCC treatment.

PMID- 29019376
TI  - Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism.

PMID- 29019370
TI  - Evaluation and optimization of reduction and alkylation methods to maximize
      peptide identification with MS-based proteomics.
AB  - Mass spectrometry (MS) has become an increasingly important technique to analyze
      proteins. In popular bottom-up MS-based proteomics, reduction and alkylation are
      routine steps to facilitate peptide identification. However, incomplete reactions
      and side reactions may occur, which compromise the experimental results. In this
      work, we systematically evaluated the reduction step with commonly used reagents,
      i.e., dithiothreitol, 2-mercaptoethanol, tris(2-carboxyethyl)phosphine, or tris(3
      hydroxypropyl)phosphine, and alkylation with iodoacetamide, acrylamide, N
      ethylmaleimide, or 4-vinylpyridine. By using digested peptides from a yeast whole
      cell lysate, the number of proteins and peptides identified were very similar
      using four different reducing reagents. The results from four alkylating
      reagents, however, were dramatically different with iodoacetamide giving the
      highest number of peptides with alkylated cysteine and the lowest number of
      peptides with incomplete cysteine alkylation and side reactions. Alkylation
      conditions with iodoacetamide were further optimized. To identify more peptides
      with cysteine, thiopropyl-sepharose 6B resins were used to enrich them, and the
      optimal conditions were employed for the reduction and alkylation. The enrichment
      resulted in over three times more cysteine-containing peptides than without
      enrichment. Systematic evaluation of the reduction and alkylation with different
      reagents can aid in a better design of bottom-up proteomic experiments.

PMID- 29019377
TI  - Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism.

PMID- 29019378
TI  - Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism.

PMID- 29019379
TI  - Special Smiles: Sports Dentistry and the Special Needs Athlete.
AB  - There is a need to expand dental services to underserved populations, such as
      athletes with intellectual and developmental disabilities. This review introduces
      dentists to this need by sharing the direction taken by the Special Smiles
      program of Special Olympics and addressing the need to educate special needs
      athletes on prevention and care of sports-related mouth injuries.

PMID- 29019380
TI  - Save Our Smiles.

PMID- 29019381
TI  - My Interest in Sports Dentistry.

PMID- 29019382
TI  - Beyond the Mouthguard: Sports Dentistry's Role in Nutrition, Prevention and
      Social Advocacy.

PMID- 29019383
TI  - The Dentist and the Athletic Trainer: A Winning Team for Oral Health Care.
AB  - Oral health is a key concern for student athletes. The dentist is the primary
      oral health care provider. Athletic trainers (ATs) are health professionals who
      have a primary care role for the student athlete. They are often the first to
      respond when dental trauma occurs in athletics. This paper informs dentists and
      ATs about each other and includes best practice in the care of athletes, which
      can be improved through interprofessional collaboration between dentists and ATs.

PMID- 29019384
TI  - Sports Dentistry: A Different Perspective

PMID- 29019385
TI  - Keeping Politics Out of the Dental Office.

PMID- 29019386
TI  - Antimicrobial Peptide-Polymer Conjugates with High Activity: Influence of Polymer
      Molecular Weight and Peptide Sequence on Antimicrobial Activity, Proteolysis, and
      Biocompatibility.
AB  - We report the synthesis, characterization, activity, and biocompatibility of a
      novel series of antimicrobial peptide-polymer conjugates. Using parent peptide
      aurein 2.2, we designed a peptide array (~100 peptides) with single and multiple
      W and R mutations and identified antimicrobial peptides (AMPs) with potent
      activity against Staphylococcus aureus (S. aureus). These novel AMPs were
      conjugated to hyperbranched polyglycerols (HPGs) of different molecular weights
      and number of peptides to improve their antimicrobial activity and toxicity. The
      cell and blood compatibility studies of these conjugates demonstrated better
      properties than those of the AMP alone. However, conjugates showed lower
      antimicrobial activity in comparison to that of peptides, as determined from
      minimal inhibition concentrations (MICs) against S. aureus, but considerably
      better than that of the available polymer-AMP conjugates in the literature. In
      addition to measuring MICs and characterizing the biocompatibility, circular
      dichroism spectroscopy was used to investigate the interaction of the novel
      conjugates with model bacterial biomembranes. Moreover, the novel conjugates were
      exposed to trypsin to evaluate their stability. It was found that the conjugates
      resist proteolysis in comparison with unprotected peptides. The peptide
      conjugates were active in serum and whole blood. Overall, the results show that
      combining a highly active AMP and low-molecular-weight HPG yields bioconjugates
      with excellent biocompatibility, MICs below 100 MUg/mL, and proteolytic
      stability, which could potentially improve its utility for in vivo applications.

PMID- 29019387
TI  - Surfing Silicon Nanofacets for Cold Cathode Electron Emission Sites.
AB  - Point sources exhibit low threshold electron emission due to local field
      enhancement at the tip. In the case of silicon, however, the realization of tip
      emitters has been hampered by unwanted oxidation, limiting the number of emission
      sites and the overall current. In contrast to this, here, we report the
      fascinating low threshold (~0.67 V MUm-1) cold cathode electron emission from
      silicon nanofacets (Si-NFs). The ensembles of nanofacets fabricated at different
      time scales, under low energy ion impacts, yield tunable field emission with a
      Fowler-Nordheim tunneling field in the range of 0.67-4.75 V MUm-1. The local
      probe surface microscopy-based tunneling current mapping in conjunction with
      Kelvin probe force microscopy measurements revealed that the valleys and a part
      of the sidewalls of the nanofacets contribute more to the field emission process.
      The observed lowest turn-on field is attributed to the absence of native oxide on
      the sidewalls of the smallest facets as well as their lowest work function. In
      addition, first-principle density functional theory-based simulation revealed a
      crystal orientation-dependent work function of Si, which corroborates well with
      our experimental observations. The present study demonstrates a novel way to
      address the origin of the cold cathode electron emission sites from Si-NFs
      fabricated at room temperature. In principle, the present methodology can be
      extended to probe the cold cathode electron emission sites from any
      nanostructured material.

PMID- 29019388
TI  - Fe3S4 Nanoparticles Wrapped in an rGO Matrix for Promising Energy Storage:
      Outstanding Cyclic and Rate Performance.
AB  - Iron sulfides/oxides/fluorides have been profoundly investigated as electrodes
      for rechargeable batteries recently in view of their high-theory capacities, low
      cost, and environmentally benign nature. Here, Fe3S4 nanoparticles (NPs) wrapped
      in reduced graphene oxide (Fe3S4 NPs@rGO) have been obtained using a simple one
      pot hydrothermal approach, which is characterized using various techniques. As
      the anode for Li-ion batteries, Fe3S4 NPs@rGO displays a reversible discharge
      capacity of 950 mA h/g after 100 cycles at 0.1 A/g, and 720 mA h/g capacity can
      be achieved after 800 cycles even at 1 A/g. Even at 10 A/g, 462 mA h/g capacity
      can be maintained. The excellent electrochemical properties for Fe3S4 NPs@rGO can
      be ascribed to a collaborative effect between Fe3S4 NPs and an rGO matrix, which
      possess high Li-ion storage ability and excellent conductivity, respectively.

PMID- 29019389
TI  - Intracellular Protein Delivery System Using a Target-Specific Repebody and
      Translocation Domain of Bacterial Exotoxin.
AB  - With the high efficacy of protein-based therapeutics and plenty of intracellular
      drug targets, cytosolic protein delivery in a cell-specific manner has attracted
      considerable attention in the field of precision medicine. Herein, we present an
      intracellular protein delivery system based on a target-specific repebody and the
      translocation domain of Pseudomonas aeruginosa exotoxin A. The delivery platform
      was constructed by genetically fusing an EGFR-specific repebody as a targeting
      moiety to the translocation domain, while a protein cargo was fused to the C
      terminal end of the delivery platform. The delivery platform was revealed to
      efficiently translocate a protein cargo to the cytosol in a target-specific
      manner. We demonstrate the utility and potential of the delivery platform by
      showing a remarkable tumor regression with negligible toxicity in a xenograft
      mice model when gelonin was used as the cytotoxic protein cargo. The present
      platform can find wide applications to the cell-selective cytosolic delivery of
      diverse proteins in many areas.

PMID- 29019390
TI  - Correction to "Pressure-Sensitive and Conductive Carbon Aerogels from Poplars
      Catkins for Selective Oil Absorption and Oil/Water Separation".

PMID- 29019392
TI  - One-Step Synthesis of Rox-DNA Functionalized CdZnTeS Quantum Dots for the Visual
      Detection of Hydrogen Peroxide and Blood Glucose.
AB  - As the blood glucose concentration is an important clinical parameter of
      diabetes, the rapid and effective detection of blood glucose is very significant
      for monitoring and managing diabetes. Here, a facile method to prepare Rox-DNA
      functionalized CdZnTeS quantum dots (QDs) was developed. The Rox-DNA
      functionalized CdZnTeS QDs were prepared by a one-pot hydrothermal method through
      phosphorothioate DNA bound to QDs, which were employed as a ratiometric
      fluorescent probe for the rapid and sensitive detection of H2O2 and glucose.
      Compared with the traditional multistep construction of ratiometric fluorescent
      probes, this presented approach is simpler and more effective without chemical
      modification and complicated separation. The CdZnTeS QDs with green fluorescence
      is specifically sensitive to H2O2, while the red fluorescence of Rox is
      invariable. H2O2 is the product from the oxidation of glucose catalyzed by
      glucose oxidase (GOx). Therefore, a facile method to detect H2O2 and glucose with
      a detection limit of 0.075 MUM for H2O2 and 0.042 MUM for glucose was developed.
      In addition, this proposed probe has been employed for the detection of glucose
      in human serum with a satisfactory result. Moreover, this probe has been used for
      visual detection, and the health and diabetics can be distinguished by the naked
      eye. Meanwhile, this nanoprobe is also generalizable and can be extended to the
      detection of many other H2O2-mediated analytes.

PMID- 29019391
TI  - Fibrous Nanozyme Dressings with Catalase-Like Activity for H2O2 Reduction To
      Promote Wound Healing.
AB  - The concentrations of the redox pair hydrogen peroxide (H2O2) and oxygen (O2) can
      promote or decelerate the progression and duration of the wound healing process.
      Although H2O2 can reach critically high concentrations and prohibit healing, a
      sufficient O2 inflow to the wound is commonly desired. Herein, we describe the
      fabrication and use of a membrane that can contemptuously decrease H2O2 and
      increase O2 levels. Therefore, hematite nanozyme particles were integrated into
      electrospun and cross-linked poly(vinyl alcohol) membranes. Within the dual
      compound membrane, the polymeric mesh provides a porous scaffold with high water
      permeability and the nanozymes act as a catalyst with catalase-like activity that
      can efficiently convert H2O2 into O2, as shown by a catalase assay. When
      comparing the growth of fibroblasts at an H2O2 concentration of 50 MUM, the
      growth was largely enhanced when applying the nanozyme dressing. Thus,
      application of the nanozyme dressing can significantly reduce the harmful effect
      of higher H2O2 concentrations. The described catalytic membranes could be used in
      the future to provide an improved environment for cell proliferation in wounds
      and thus applied as advanced wound healing dressings.

PMID- 29019393
TI  - Tough, Stretchable, Compressive Novel Polymer/Graphene Oxide Nanocomposite
      Hydrogels with Excellent Self-Healing Performance.
AB  - Designing hydrogels with high mechanical properties without sacrificing their
      self-healing efficiencies remains great challenges. We have fabricated cationic
      polyacrylamide/graphene oxide (GO) hydrogels by free-radical polymerization of
      acrylamide (AM) and 2-(dimethylamino)ethylacrylatemethochloride (DAC) in the
      presence of GO. The mechanical properties and self-healing ability can be tuned
      by the GO content and the mass ratio of AM and DAC. The ionic bonds between DAC
      and GO and the hydrogen bonds between AM and GO can efficiently dissipate energy
      and rebuild the networks. The resulting composite hydrogels possess high
      stiffness (Young's modulus: ~1.1 MPa), high toughness (~9.3 MJ m-3), and high
      fatigue resistance, as well as high self-healing efficiency (>92% of tensile
      strength, >99% of tensile strain and >93% of toughness). In addition, the
      completely dried hydrogels can recover their original mechanical values by
      spraying water and still possess outstanding self-healing efficiency. Our design
      can provide better fundamental understanding of physical properties of hydrogels
      and should enable the development of tough, self-healing hydrogels for practical
      applications.

PMID- 29019394
TI  - Studies on 16,17-Pyrazoline Substituted Heterosteroids as Anti-Alzheimer and Anti
      Parkinsonian Agents Using LPS Induced Neuroinflammation Models of Mice and Rats.
AB  - Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common forms
      of neurodegenerative disorders. Dehydroepiandrosterone (DHEA) has been reported
      as a neuroprotective steroid useful in the therapeutic management of
      neurodegenerative disorders such as AD and PD. Herein we report the synthesis and
      evaluation of a new series of 16,17-pyrazolinyl DHEA analogues 2-4a-d as
      neuroprotective agents using LPS-induced neuroinflammation animal models.
      Treatment with the pyrazoline substituted steroids considerably improved the LPS
      induced learning, memory and movement deficits in animal models. Suppression of
      biochemical parameters of oxidative and nitrosative stress, acetylcholinesterase
      activity, and TNF-alpha levels was also observed. 16,17-Pyrazolinyl steroids 2c
      4c substituted with a 4-pyridyl moiety at the 5-position of the heterocyclic ring
      were found to be the most potent agents and produced neuroprotective effects
      better than standard drugs celecoxib and dexamethasone. Of these pyrazoline
      substituted steroids, the N-acetyl analogue 3c displayed neuroprotective effects
      better than N-phenyl (4c), which in turn showed potency more than N-unsubstituted
      analogue 2c.

PMID- 29019395
TI  - Selenization of Cu2ZnSnS4 Enhanced the Performance of Dye-Sensitized Solar Cells:
      Improved Zinc-Site Catalytic Activity for I3.
AB  - Cu2ZnSnS4 (CZTS) and Cu2ZnSn(S,Se)4 (CZTSSe) as promising photovoltaic materials
      have drawn much attention because they are environmentally benign and earth
      abundant elements. In this work, the monodispersed, low-cost Cu2ZnSnS4
      nanocrystals with small size have been controllably synthesized via a wet
      chemical routine. And CZTSSe could be easily prepared after selenization of CZTS.
      When they are employed as counter electrodes (CEs) for dye-sensitized solar cells
      (DSSCs), the power conversion efficiency (PCE) has been improved from 3.54% to
      7.13% as CZTS is converted to CZTSSe, which is also compared to that of Pt
      (7.62%). The exact reason for the enhanced catalytic activity of I3- is discussed
      with the work function and density functional theory (DFT) when CZTSSe converted
      from CZTS. The results of a Kelvin probe suggest that the work function of CZTSSe
      (5.61 eV) is closer to that of Pt (5.65 eV) and higher than that of CZTS, which
      matched the redox shuttle potential better. According to the theory calculation,
      all the atomic and bond populations changed significantly when Se replaced partly
      the S on the CZTS system, especially in the Zn site. During the catalytic process
      as CEs, the adsorption energy obviously increased compared to those at other
      sites when I3- adsorbed on the Zn site in CZTSSe. So, Zn plays an important role
      for the reduction of I3- after CZTS is converted to CZTSSe. Based on above
      analysis, the reason for enhanced performance of DSSCs when CZTS converted to
      CZTSSe is mainly due to the enhancement of Zn-site activity. This work is
      beneficial for understanding the catalytic reaction mechanism of CZTS(Se) as CEs
      of DSSCs.

PMID- 29019397
TI  - The Interface Structure of FeSe Thin Film on CaF2 Substrate and its Influence on
      the Superconducting Performance.
AB  - The investigations into the interfaces in iron selenide (FeSe) thin films on
      various substrates have manifested the great potential of showing high
      temperature-superconductivity in this unique system. In present work, we obtain
      FeSe thin films with a series of thicknesses on calcium fluoride (CaF2) (100)
      substrates and glean the detailed information from the FeSe/CaF2 interface by
      using scanning transmission electron microscopy (STEM). Intriguingly, we have
      found the universal existence of a calcium selenide (CaSe) interlayer with a
      thickness of approximate 3 nm between FeSe and CaF2 in all the samples, which is
      irrelevant to the thickness of FeSe layers. A slight Se deficiency occurs in the
      FeSe layer due to the formation of CaSe interlayer. This Se deficiency is
      generally negligible except for the case of the ultrathin FeSe film (8 nm in
      thickness), in which the stoichiometric deviation from FeSe is big enough to
      suppress the superconductivity. Meanwhile, in the overly thick FeSe layer (160 nm
      in thickness), vast precipitates are found and recognized as Fe-rich phases,
      which brings about degradation in superconductivity. Consequently, the thickness
      dependence of superconducting transition temperature (Tc) of FeSe thin films is
      investigated and one of our atmosphere-stable FeSe thin film (127 nm) possesses
      the highest Tconset/Tczero as 15.1 K/13.4 K on record to date in the class of
      FeSe thin film with practical thickness. Our results provide a new perspective
      for exploring the mechanism of superconductivity in FeSe thin film via high
      resolution STEM. Moreover, approaches that might improve the quality of FeSe/CaF2
      interfaces are also proposed for further enhancing the superconducting
      performance in this system.

PMID- 29019396
TI  - The Promise and Challenge of In Vivo Delivery for Genome Therapeutics.
AB  - CRISPR-based genome editing technologies are poised to enable countless new
      therapies to prevent, treat, or cure diseases with a genetic basis. However, the
      safe and effective delivery of genome editing enzymes represents a substantial
      challenge that must be tackled to enable the next generation of genetic
      therapies. In this Review, we summarize recent progress in developing enzymatic
      tools to combat genetic disease and examine current efforts to deliver these
      enzymes to the cells in need of correction. Viral vectors already in use for
      traditional gene therapy are being applied to enable in vivo CRISPR-based
      therapeutics, as are emerging technologies such as nanoparticle-based delivery of
      CRISPR components and direct delivery of preassembled RNA-protein complexes.
      Success in these areas will allow CRISPR-based genome editing therapeutics to
      reach their full potential.

PMID- 29019399
TI  - Ingestion of Microplastics by Freshwater Tubifex Worms.
AB  - Microplastic contamination of the aquatic environment is a global issue.
      Microplastics can be ingested by organisms leading to negative physiological
      impacts. The ingestion of microplastics by freshwater invertebrates has not been
      reported outside the laboratory. Here we demonstrate the ingestion of
      microplastic particles by Tubifex tubifex from bottom sediments in a major urban
      waterbody fed by the River Irwell, Manchester, UK. The host sediments had
      microplastic concentrations ranging from 56 to 2543 particles kg-1. 87% of the
      Tubifex-ingested microplastic particles were microfibers (55-4100 MUm in length),
      while the remaining 13% were microplastic fragments (50-4500 MUm in length). FT
      IR analysis revealed ingestion of a range of polymers, including polyester and
      acrylic fibers. While microbeads were present in the host sediment matrix, they
      were not detected in Tubifex worm tissue. The mean concentration of ingested
      microplastics was 129 +/- 65.4 particles g-1 tissue. We also show that Tubifex
      worms retain microplastics for longer than they retain other particulate
      components of the ingested sediment matrix. Microplastic ingestion by Tubifex
      worms poses a significant risk for trophic transfer and biomagnification of
      microplastics up the aquatic food chain.

PMID- 29019398
TI  - Exploration of a Variety of Copper Molybdate Coordination Hybrids Based on a
      Flexible Bis(1,2,4-triazole) Ligand: A Look through the Composition-Space
      Diagram.
AB  - We investigated the coordination ability of the bis(1,2,4-triazolyl) module,
      tr2pr = 1,3-bis(1,2,4-triazol-4-yl)propane, toward the engineering of solid-state
      structures of copper polyoxomolybdates utilizing a composition space diagram
      approach. Different binding modes of the ligand including [N-N]-bridging and N
      terminal coordination and the existence of favorable conformation forms
      (anti/anti, gauche/anti, and gauche/gauche) resulted in varieties of mixed metal
      CuI/MoVI and CuII/MoVI coordination polymers prepared under hydrothermal
      conditions. The composition space analysis employed was aimed at both the
      development of new coordination solids and their crystallization fields through
      systematic changes of the reagent ratios [copper(II) and molybdenum(VI) oxide
      precursors and the tr2pr ligand]. Nine coordination compounds were synthesized
      and structurally characterized. The diverse coordination architectures of the
      compounds are composed of cationic fragments such as [CuII3(MU2-OH)2(MU2-tr)2]4+,
      [CuII3(MU2-tr)6]6+, [CuII2(MU2-tr)3]4+, etc., connected to polymeric arrays by
      anionic species (molybdate MoO42-, isomeric alpha-, delta-, and beta
      octamolybdates {Mo8O26}4- or {Mo8O28H2}6-). The inorganic
      copper(I,II)/molybdenum(VI) oxide matrix itself forms discrete or low-dimensional
      subtopological motifs (0D, 1D, or 2D), while the organic spacers interconnect
      them into higher-dimensional networks. The 3D coordination hybrids show moderate
      thermal stability up to 230-250  degrees C, while for the 2D compounds, the
      stability of the framework is distinctly lower (~190  degrees C). The magnetic
      properties of the most representative samples were investigated. The magnetic
      interactions were rationalized in terms of analyzing the planes of the magnetic
      orbitals.

PMID- 29019400
TI  - Graphene Nanoplatelet-Polymer Chemiresistive Sensor Arrays for the Detection and
      Discrimination of Chemical Warfare Agent Simulants.
AB  - A cross-reactive array of semiselective chemiresistive sensors made of polymer
      graphene nanoplatelet (GNP) composite coated electrodes was examined for
      detection and discrimination of chemical warfare agents (CWA). The arrays employ
      a set of chemically diverse polymers to generate a unique response signature for
      multiple CWA simulants and background interferents. The developed sensors' signal
      remains consistent after repeated exposures to multiple analytes for up to 5 days
      with a similar signal magnitude across different replicate sensors with the same
      polymer-GNP coating. An array of 12 sensors each coated with a different polymer
      GNP mixture was exposed 100 times to a cycle of single analyte vapors consisting
      of 5 chemically similar CWA simulants and 8 common background interferents. The
      collected data was vector normalized to reduce concentration dependency, z-scored
      to account for baseline drift and signal-to-noise ratio, and Kalman filtered to
      reduce noise. The processed data was dimensionally reduced with principal
      component analysis and analyzed with four different machine learning algorithms
      to evaluate discrimination capabilities. For 5 similarly structured CWA simulants
      alone 100% classification accuracy was achieved. For all analytes tested 99%
      classification accuracy was achieved demonstrating the CWA discrimination
      capabilities of the developed system. The novel sensor fabrication methods and
      data processing techniques are attractive for development of sensor platforms for
      discrimination of CWA and other classes of chemical vapors.

PMID- 29019401
TI  - N,N'-Disubstituted Indigos as Readily Available Red-Light Photoswitches with
      Tunable Thermal Half-Lives.
AB  - Some rare indigo derivatives have been known for a long time to be photochromic
      upon irradiation with red light, which should be advantageous for many
      applications. However, the absence of strategies to tune their thermal half-lives
      by modular molecular design as well as the lack of proper synthetic methods to
      prepare a variety of such molecules from the parent indigo dye have so far
      precluded their use. In this work, several synthetic protocols for N
      functionalization have been developed, and a variety of N-alkyl and N-aryl indigo
      derivatives have been prepared. By installation of electron-withdrawing
      substituents on the N-aryl moieties, the thermal stability of the Z-isomers could
      be enhanced while maintaining the advantageous photoswitching properties upon
      irradiation with red light (660 nm LED). Both experimental data and computational
      results suggest that the ability to tune thermal stability without affecting the
      dyes' absorption maxima originates from the twisted geometry of the N-aryl
      groups. The new indigo photoswitches reported are expected to have a large impact
      on the development of optical methods and applications in both life and material
      sciences.

PMID- 29019402
TI  - A Systematic Analysis of the Binding Affinity between the Pim-1 Kinase and Its
      Inhibitors Based on the MM/3D-RISM/KH Method.
AB  - A systematic study of the binding affinities of 16 lead compounds targeting the
      Pim-1 kinase based on the 3D-RISM/KH theory and MD simulations is reported. The
      results show a correlation coefficient R = 0.69 between the theoretical and
      experimental values of the binding free energy. This demonstrates that the method
      is applicable to the problem of compound screening and lead optimization, for
      which relative values of the free energy among the compounds have significance.
      We elucidate the contribution of the ligand fragments to the binding free energy.
      Our results indicate that the interactions between the residues and the
      triazolo[4,3-b]pyridazine scaffold as well as the phenyl ring of the ligand
      molecule make significant contributions to stabilization of the complex. Using
      the 3D-RISM/KH theory, we further analyze the probability distribution of a
      ligand fragment around the protein-ligand complex in which the substituent around
      the phenyl ring is removed from the ligand. The results demonstrate that the 3D
      RISM/KH theory is capable of predicting the position of substitution on a ligand
      that has a higher affinity to a target protein.

PMID- 29019403
TI  - Tertiary Interactions in the Unbound Guanine-Sensing Riboswitch Focus Functional
      Conformational Variability on the Binding Site.
AB  - Riboswitches are genetic regulatory elements mainly found in bacteria, which
      regulate gene expression based on the availability of a ligand. Purine-sensing
      riboswitches, including the guanine-sensing riboswitch (Gsw), possess tertiary
      interactions connecting the L2 and L3 loops. These interactions are important for
      ligand binding to the aptamer. However, atomic-level structural knowledge about
      the unbound state and how the tertiary interactions influence the conformational
      heterogeneity of the aptamer is still scarce. We performed replica exchange
      molecular dynamics simulations of the aptamer domain of wild-type Gsw and a
      G37A/C61U mutant, which exhibits destabilized tertiary interactions, at different
      Mg2+ concentrations with an aggregate simulation time of ~16 MUs, and
      subsequently obtained free-energy landscapes. Our data provide evidence that
      suggests that the unbound state of wild-type Gsw is conformationally rather
      homogeneous from a global viewpoint, yet the ligand binding site shows
      functionally necessary mobility required for ligand binding. For the mutant, the
      data suggest a heterogeneous ensemble, in particular without Mg2+. Hence, the
      tertiary interactions focus functional conformational variability on the binding
      site region of wild-type Gsw. Our data allow speculating that already the
      weakening of the tertiary interactions by two hydrogen bonds shifts the kinetics
      of folding from downhill folding without traps or intermediate states for wild
      type Gsw to a folding including intermediates and misfolded structures for the
      mutant. A slowed-down folding of the aptamer might favor a decision during
      transcriptional regulation for the off-path, even if the ligand binds.

PMID- 29019404
TI  - Unexpected Competition between Antiferromagnetic and Ferromagnetic States in
      Hf2MnRu5B2: Predicted and Realized.
AB  - Materials "design" is increasingly gaining importance in the solid-state
      materials community in general and in the field of magnetic materials in
      particular. Density functional theory (DFT) predicted the competition between
      ferromagnetic (FM) and antiferromagnetic (AFM) ground states in a ruthenium-rich
      Ti3Co5B2-type boride (Hf2MnRu5B2) for the first time. Vienna ab initio simulation
      package (VASP) total energy calculations indicated that the FM model was
      marginally more stable than one of the AFM models (AFM1), indicating very weak
      interactions between magnetic 1D Mn chains that can be easily perturbated by
      external means (magnetic field or composition). The predicted phase was then
      synthesized by arc-melting and characterized as Hf2Mn1-xRu5+xB2 (x = 0.27).
      Vibrating-scanning magnetometry shows an AFM ground state with TN ~ 20 K under
      low magnetic field (0.005 T). At moderate-to-higher fields, AFM ordering vanishes
      while FM ordering emerges with a Curie temperature of 115 K. These experimental
      outcomes confirm the weak nature of the interchain interactions, as predicted by
      DFT calculations.

PMID- 29019405
TI  - Chemical Constituents of Bryophytes: Structures and Biological Activity.
AB  - Comparatively little attention has been paid to the bryophytes for use in the
      human diet or medicine in spite of the presence of 23 000 species globally.
      Several hundred new compounds have been isolated from the liverworts
      (Marchantiophyta), and more than 40 new carbon skeletons of terpenoids and
      aromatic compounds were found. Most of the liverworts studied elaborate
      characteristic odiferous, pungent, and bitter-tasting compounds, of which many
      show antimicrobial, antifungal, antiviral, allergic contact dermatitis,
      cytotoxic, insecticidal, anti-HIV, plant growth regulatory, neurotrophic, NO
      production and superoxide anion radical release inhibitory, muscle relaxing,
      antiobesity, piscicidal, and nematocidal activities. The biological effects
      ascribed to the liverworts are mainly due to lipophilic sesqui- and diterpenoids,
      phenolic compounds, and polyketides, which are the principal constituents of
      their oil bodies. Some mosses and liverworts produce significant levels of
      vitamin B2 and tocopherols, as well as prostaglandin-like highly unsaturated
      fatty acids. The most characteristic chemical phenomenon of the liverworts is
      that most of the sesqui- and diterpenoids are enantiomers of those found in
      higher plants. In this review, the chemical constituents and potential medicinal
      uses of bryophytes are discussed.

PMID- 29019406
TI  - Discovery of the High-Pressure Phase of Ba3W2O9 and Determination of Its Crystal
      Structure.
AB  - A new polymorphism of Ba3W2O9 is discovered with the use of a high-pressure
      synthesis technique and its crystal structure is determined by single-crystal X
      ray diffraction and transmission electron microscopy. The crystal structure was
      isostructural with that of Ba3Re2O9, having a hexagonal unit cell of R3m symmetry
      with a = 0.574060(10) nm and c = 2.08256(4) nm. The high-pressure (HP) phase is
      obtained from a transformation of an ambient-pressure (AP) phase of the compound,
      which has the Cs3Tl2Cl9-type structure. The most notable change in the
      transformation is the connection of WO6 octahedra. The HP phase has corner
      sharing octahedra, which form a bilayer structure, while the AP phase has face
      sharing octahedra of isolated [W2O9] dimers. This type of the structural phase
      transition is unreported although it is possibly that a sequence of high-pressure
      structural transformations occurs for similar chemical compositions. The HP phase
      has W ions in WO6 octahedra with an unusual off-center displacement; although the
      displacement is slightly relaxed compared with that of the AP phase. The off
      center displacement suggests strong hybridization between the W 5d orbitals and O
      2p orbitals.

PMID- 29019407
TI  - A Combined Experimental and Theoretical Study on the Circular Dichroism of
      Staggered and Eclipsed Forms of Dimethoxy[2.2]-, [3.2]-, and [3.3]Pyridinophanes
      and Their Protonated Forms.
AB  - The circular dichroisms (CDs) of dimethoxy[2.2]-, [3.2]-, and [3.3]pyridinophanes
      and their protonated forms were investigated experimentally and theoretically.
      Characteristic multisignate Cotton effects (CEs), typical for planar chiral
      cyclophane derivatives, were observed. The CD spectral pattern was quite
      comparable for the staggered forms of [2.2]-, [3.2]-, and [3.3]cyclophanes, but
      significantly differed for the eclipsed forms. More interestingly, the patterns
      resembled, but the CE signs were practically opposite between staggered and
      eclipsed [2.2]pyridinophanes. Upon protonation, the signs of most CEs were
      inverted in both forms of cyclophanes, due to the reversal of dipole moment in
      the pyridine against the pyridinium moiety. Such a change in CD spectrum upon
      protonation was not apparent in [3.2]pyridinophane, and the CD spectral behavior
      was more complex in [3.3]pyridinophanes. The variation of CD caused by the
      protonation/deprotonation process was temperature-dependent and hence utilized as
      a thermal sensor. The protonated forms of the homologous pyridinophanes with
      different tether lengths in staggered and eclipsed forms served as a model system
      for systematically studying the cation-pi interaction and its effects on
      chiroptical properties. A steady increase of electronic interaction became
      apparent for the smaller-sized cyclophanes from the increased excitation energy
      and electronic coupling element of the charge-transfer (CT) band, while the
      observed CE at the CT band was a more complex function of the original transition
      dipole of donor/acceptor pair and linker atoms, as well as the strength of the
      electronic interaction.

PMID- 29019408
TI  - Cleaving Off Uranyl Oxygens through Chelation: A Mechanistic Study in the Gas
      Phase.
AB  - Recent efforts to activate the strong uranium-oxygen bonds in the dioxo uranyl
      cation have been limited to single oxo-group activation through either uranyl
      reduction and functionalization in solution, or by collision induced dissociation
      (CID) in the gas-phase, using mass spectrometry (MS). Here, we report and
      investigate the surprising double activation of uranyl by an organic ligand,
      3,4,3-LI(CAM), leading to the formation of a formal U6+ chelate in the gas-phase.
      The cleavage of both uranyl oxo bonds was experimentally evidenced by CID, using
      deuterium and 18O isotopic substitutions, and by infrared multiple photon
      dissociation (IRMPD) spectroscopy. Density functional theory (DFT) computations
      predict that the overall reaction requires only 132 kJ/mol, with the first oxygen
      activation entailing about 107 kJ/mol. Combined with analysis of similar, but
      unreactive ligands, these results shed light on the chelation-driven mechanism of
      uranyl oxo bond cleavage, demonstrating its dependence on the presence of ligand
      hydroxyl protons available for direct interactions with the uranyl oxygens.

PMID- 29019409
TI  - Genome Mining and Activation of a Silent PKS/NRPS Gene Cluster Direct the
      Production of Totopotensamides.
AB  - A 92 kb silent hybrid polyketide and nonribosomal peptide gene cluster in marine
      derived Streptomyces pactum SCSIO 02999 was activated by genetically manipulating
      the regulatory genes, including the knockout of two negative regulators (totR5
      and totR3) and overexpression of a positive regulator totR1, to direct the
      production of the known totopotensamides (TPMs) A (1) and B (3) and a novel
      sulfonate-containing analogue TPM C (2). Inactivation of totG led to accumulation
      of TPM B (3) lacking the glycosyl moiety, which indicated TotG as a dedicated
      glycosyltransferase in the biosynthesis of 1 and 2.

PMID- 29019410
TI  - Calix[n]triazoles and Related Conformational Studies.
AB  - Calix[n]triazoles are developed as new derivatives in the calixarene family.
      Calixtriazole compounds 2-4 are synthesized using an iterative convergent
      strategy including an inter-/intramolecular copper(I)-catalyzed azide-alkyne
      cycloaddition reaction. Solid-state structures are clearly refined to give 1,2
      alternate and partial cone conformations for calix[4]triazole and
      calix[5]triazole, respectively. Theoretical studies based on density functional
      theory (DFT) calculations indicated that intermolecular interactions are crucial
      in determining the conformers of the crystals, and the most stable conformers of
      calix[4]triazole, calix[5]triazole, and calix[6]triazole in the monomeric forms
      are 1,3-alternate, 1,3-alternate, and 1,3,5-alternate, respectively.

PMID- 29019411
TI  - Aromatic Hybrid Foldamer with a Hydrophilic Helical Cavity Capable of
      Encapsulating Glucose.
AB  - An indolocarbazole-naphthyridine hybrid oligomer capable of adopting a stable
      helical conformation was prepared, and its folding properties were thoroughly
      studied in the solid state and in solution. As a result of folding, a hydrophilic
      cavity was generated inside the helix wherein monosaccharides were able to be
      encapsulated in the order of glucose (9.6 * 104 M-1) > galactose (1.0 * 104 M-1)
      ? mannose (~0) in 10% (v/v) DMSO/CH2Cl2.

PMID- 29019412
TI  - Associations between HIV-related stigma, self-esteem, social support, and
      depressive symptoms in Namibia.
AB  - OBJECTIVE: The current study sought to investigate the association between HIV
      related stigma, self-esteem, social support, and depression of people living with
      HIV and AIDS (PLWHA) in Namibia. METHOD: Purposive sampling was used to recruit a
      total of 124 men and women living with HIV/AIDS in the Katima Mulilo region of
      northern Namibia. A cross-sectional survey was used to collect information on
      demographics, self-esteem, social support, HIV-related stigma, and depression.
      RESULTS: Correlation analysis revealed that HIV-related stigma, self-esteem, and
      social support were all significantly correlated with depression. Further,
      Ordinary Least Squares (OLS) regression analysis indicated that HIV-related
      stigma was the largest risk factor and self-esteem was the largest protective
      factor with respect to depressive symptoms. DISCUSSION: Findings indicated the
      necessity of appropriate assessment and intervention for psychosocial distress
      among PLWHA. Helping professionals should design evidence-based interventions
      that address individual and societal challenges that impact people living with
      HIV and AIDS.

PMID- 29019413
TI  - Instrumentation for Testing Whether the Icy Moons of the Gas and Ice Giants Are
      Inhabited.
AB  - Evidence of life beyond Earth may be closer than we think, given that the
      forthcoming missions to the jovian system will be equipped with instruments
      capable of probing Europa's icy surface for possible biosignatures, including
      chemical biomarkers, despite the strong radiation environment. Geochemical
      biomarkers may also exist beyond Europa on icy moons of the gas giants. Sulfur is
      proposed as a reliable geochemical biomarker for approved and forthcoming
      missions to the outer solar system. Key Words: JUICE mission-Clipper mission
      Geochemical biomarkers-Europa-Moons of the ice giants-Geochemistry-Mass
      spectrometry. Astrobiology 17, 958-961.

PMID- 29019415
TI  - Pain characteristics of older persons with medically unexplained symptoms, older
      persons with medically explained symptoms and older persons with depression.
AB  - OBJECTIVES: The main objective of the current study is to compare chronic pain
      characteristics of older patients with Medically Unexplained Symptoms (MUS), to
      those of patients with Medically Explained Symptoms (MES), and to those of
      patients with Major Depressive Disorder (MDD). METHOD: By combining data from the
      OPUS and NESDO study, we compared pain characteristics of 102 older (>60 years)
      MUS-patients to 145 older MES-patients and 275 older MDD-patients in a case
      control study design. Group differences were analyzed using ANCOVA, adjusted for
      demographic and physical characteristics. Linear regression was applied to
      examine the association between pain characteristics and somatization (BSI-53
      somatization scale) and health anxiety (Whitely Index). RESULTS: Older MUS
      patients have approximately  two times more chance of having chronic pain when
      compared to older MES-patients (OR = 2.01; p = .013) but equal chances as opposed
      to MDD-patients. After adjustments, MUS-patients report higher pain intensity and
      disability scores and more pain locations when compared to MES-patients, but
      equal values as MDD-patients. Health anxiety and somatization levels were
      positively associated with the number of pain sites in MUS-patients, but not with
      pain severity or disability. CONCLUSION: Older MUS-patients did not differ from
      MDD-patients with respect to any of the chronic pain characteristics, but had
      more intense and disabling pain, and more pain locations when compared to older
      MES-patients.

PMID- 29019414
TI  - The TERT hypermethylated oncologic region predicts recurrence and survival in
      pancreatic cancer.
AB  - AIM: We explore the biomarker potential of the TERT hypermethylated oncologic
      region (THOR) in pancreatic cancer. MATERIALS & METHODS: We assessed the
      methylation status of THOR using the cancer genome atlas data on the cohort of
      pancreatic cancer (n = 193 patients). RESULTS: THOR was significantly
      hypermethylated in pancreatic tumor tissue when compared with the normal tissue
      used as control (p < 0.0001). Also, THOR hypermethylation could distinguish early
      stage I disease from normal tissue and was associated with worse prognosis.
      DISCUSSION:  We found that THOR is hypermethylated in pancreatic tumor tissue
      when compared with normal tissue and that THOR methylation correlates with TERT
      expression in tumor samples. CONCLUSION: Our preliminary findings support the
      diagnostic and prognostic values of THOR in pancreatic cancer.

PMID- 29019416
TI  - Communication technology adoption among older adult veterans: the interplay of
      social and cognitive factors.
AB  - OBJECTIVES: InTouch is an electronic communication platform designed to be
      accessible by computer-naive seniors. The present study explored the process of
      adoption and use of the application by seniors with and without mild cognitive
      impairment (MCI) through the lens of Social Cognitive Theory (SCT). METHOD: We
      studied adoption and use of InTouch for social communication over a 12-week
      period in a 475-bed Veteran's care facility at Sunnybrook Health Sciences Centre
      in Toronto, Canada. Eleven older adult veterans participated, six of whom had
      MCI, as indicated by their Montreal Cognitive Assessment score. Veterans were
      partnered with volunteers, each was provided with an iPad with the InTouch
      application. Qualitative data were collected through interviews, field notes, and
      direct observation. Quantitative data were collected from data logging of the
      software and medical charts. Data types and sources were triangulated and
      examined through the lens of SCT. RESULTS: A total of 2361 messages (102 videos,
      359 audios, 417 photos, 1438 texts) were sent by 10 of the 11 veterans over the
      12-week study period. There was no apparent difference in extent of adoption or
      use, between participants with and without MCI. Participants used various
      resources and techniques to learn, provided that they felt motivated to connect
      with others using the app. CONCLUSION: This pilot illustrates both the
      accessibility of InTouch and the promise of using extrinsic motivators such as
      social bonding to promote learning in institutionalized older adults with and
      without cognitive impairment, whose intrinsic motivation and self-efficacy may
      well be suffering.

PMID- 29019417
TI  - What a difference a year makes: comparing relationships between stressful life
      events, mood and life satisfaction among older adults, and their working-age
      counterparts.
AB  - OBJECTIVES: Stressful life events (SLEs) have been linked to depression, anxiety,
      and reduced life satisfaction. The inoculation hypothesis of aging suggests older
      adults may be less vulnerable to poor psychological outcomes following SLEs than
      working-age adults. The current study compared relationships between SLEs, mood
      and life satisfaction among older adults (65+), and adults aged 50-64, and
      investigated whether group identification and loneliness moderate these
      relationships. METHOD: A community-based sample of 121 Scottish participants
      responded to measures of SLEs (modified Social Readjustment Rating Scale),
      symptoms of depression and anxiety (Hospital Anxiety and Depression Scale), life
      satisfaction (Life Satisfaction Index A), group identification (Group
      Identification Scale), and loneliness (UCLA Loneliness Scale). RESULTS: In the 50
      64 age group, the number of SLEs was significantly associated with greater
      symptoms of depression and anxiety, and reduced life satisfaction. Group
      identification and loneliness did not moderate these relationships. There were no
      significant relationships in the older adult group. CONCLUSION: The finding of
      relationships in working-age, but not older adults, supports the inoculation
      hypothesis of aging. Further research to better understand changes across the
      lifespan, and inter-relationships with related variables, would be valuable from
      both theoretical and clinical perspectives.

PMID- 29019418
TI  - Texting Motivational Interviewing: A Randomized Controlled Trial of Motivational
      Interviewing Text Messages Designed to Augment Childhood Obesity Treatment.
AB  - BACKGROUND: Text messages improve health outcomes for adults engaged in weight
      management. Little is known about whether text messaging parents of children
      enrolled in obesity treatment will improve child health. METHODS: We conducted a
      2-group randomized controlled study among 101 children aged 5-12 and their
      parent/guardian enrolling in tertiary-care obesity treatment. Participants were
      randomized to standard care or standard care plus daily motivational interviewing
      based text messages. The primary outcome was change in child BMI at 3 months.
      Secondary outcomes included feasibility, health behaviors, attrition, motivation,
      and parent BMI. RESULTS: We enrolled 101 parent-child dyads and retained 81% to 3
      month follow-up. Child participants had a mean age of 9.9 years, and baseline BMI
      of 30.5 kg/m2. Half (48%) of participants were Black, and 64% of parent
      participants had a high school equivalent education or less. Ninety-nine percent
      of parents owned a mobile device with unlimited text messaging. Parents responded
      to 80% of texts, and 95% felt the texts "always" or "almost always" helped them
      make a good health decision. We observed no between-group difference in child
      zBMI from baseline to 3 months (0.0 vs. 0.2, p = 0.2). Intervention participants
      had significantly better adherence to clinic visits (3.3 visits vs. 2.1 visits/3
      months, p < 0.001). CONCLUSIONS: Parent-directed text messages did not
      significantly change child BMI. However, texting significantly reduced attrition
      for treatment visits. Nearly all parents in this racially diverse, low-income
      sample engaged in daily text messaging, making this a feasible approach.

PMID- 29019419
TI  - Prenatal Exposure to Endocrine Disruptors and Reprogramming of Adipogenesis: An
      Early-Life Risk Factor for Childhood Obesity.
AB  - Obesity is a global health problem. It is characterized by excess adipose tissue
      that results from either increase in the number of adipocytes or increase in
      adipocytes size. Adipocyte differentiation is a highly regulated process that
      involves the activation of several transcription factors culminating in the
      removal of adipocytes from the cell cycle and induction of highly specific
      proteins. Several other factors, including hormones, genes, and epigenetics, are
      among the most important triggers of the differentiation process. Although the
      main contributing factors to obesity are high caloric intake, a sedentary
      lifestyle, and genetic predisposition, strong evidence supports a role for life
      exposure to environmental pollutants. Endocrine-disrupting chemicals are
      exogenous, both natural and man-made, chemicals that disrupt the body signaling
      processes, thus interfering with the endocrine system. Several studies have shown
      that prenatal exposure to endocrine disruptors modulates the mechanisms, by which
      multipotent mesenchymal stem cells differentiate into adipocytes. This review
      discusses adipocytes differentiation and highlights the possible mechanisms of
      prenatal exposure to endocrine disruptors in reprogramming of adipogenesis and
      induction of obesity later in life. Therefore, this review provides knowledge
      that reduction of early life exposure to these chemicals could open the door for
      new strategies in the prevention of obesity, especially during childhood.

PMID- 29019420
TI  - What role does stereotactic ablative radiotherapy have in advanced castrate
      resistant prostate cancer?

PMID- 29019421
TI  - Management of acute pain in the postoperative setting: the importance of quality
      indicators.
AB  - Despite the introduction of evidence-based recommendations for postoperative pain
      management (POPM), the consensus is that pain control remains suboptimal.
      Barriers to achieving patient-satisfactory analgesia include deficient knowledge
      regarding POPM among staff, lack of instructions, insufficient pain assessments
      and sub-optimal treatment. Effective monitoring of POPM is essential to enable
      policy makers and healthcare providers to improve the quality of care. Quality
      indicators (QIs) are quantitative measures of clinical practice that can monitor,
      evaluate and guide the quality of care provided to patients. QIs can be used to
      assess various aspects relating to the care process and they have proven useful
      in improving health outcomes in diseases such as myocardial infarction. In this
      commentary we critically analyze the evidence regarding the use of QIs in acute
      POPM based upon the experience of pain specialists from Europe and the USA who
      are members of the Change Pain Advisory Board. We also undertook a literature
      review to see what has been published on QIs in acute pain with the goal of
      assessing which QIs have been developed and used, and which ones have been
      successful/unsuccessful. In the hospital sector the development and
      implementation of QIs is complex. The nature of POPM requires a highly trained,
      multidisciplinary team and it is at this level that major improvements can be
      made. Greater involvement of patients regarding pain management is also seen as a
      priority area for improving clinical outcomes. Changes in structure and processes
      to deliver high-level quality care need to be regularly audited to ensure
      translation into better outcomes. QIs can help drive this process by providing an
      indicator of current levels of performance. In addition, outcomes QIs can be used
      to benchmark levels of performance between different healthcare providers.

PMID- 29019423
TI  - National hyperlipidemia management policies improve lipid target attainment in
      clinical practice.

PMID- 29019422
TI  - Pharmacotherapy of mood disorders and psychosis in pre- and post-natal women.
AB  - INTRODUCTION: Untreated mood and psychotic disorders can have substantial adverse
      impacts on the patient, the fetus and the family, while treatment can ameliorate
      such problems. To address concerns by clinicians about the risks of psychotropic
      medications, this review addresses the risk/benefit analysis of somatic therapies
      for psychiatric disorders during pregnancy and lactation. Areas covered: All
      available research was reviewed on the impact on pregnancy and breastfeeding of
      mood and psychotic disorders, and of antidepressants, mood stabilizers,
      antipsychotic drugs, and electroconvulsive therapy. References cited in other
      reviews, case series, formal studies, pharmacologic discussions, and theoretical
      pieces were added. Available case control and other studies were critically
      reviewed and diverse explanations for their findings were considered. Expert
      opinion: The potential benefits of treatment of mood and psychotic disorders
      often outweigh the risks after alternative therapies have been considered. Some
      medications, particularly paroxetine and valproate, pose greater risks during
      pregnancy, while the teratogenic risks of lithium have probably been overstated.
      There is more experience with first than with second generation antipsychotic
      drugs during pregnancy and lactation. Nursing an infant is possible while taking
      a number of antidepressants, mood stabilizers or antipsychotic drugs.

PMID- 29019425
TI  - Communication of behaviour change interventions: Can they be recognised from
      written descriptions?
AB  - OBJECTIVE: Communication of the content of a behaviour change intervention (BCI)
      involves clear description followed by appropriate recognition and
      interpretation. We investigated accuracy of recognition of BCI descriptions and
      the effects of training in the behaviour change taxonomy BCTTv1. METHODS:
      Materials were 166 written descriptions of two BCIs previously written by 166
      separate writers after viewing a video of the BCI. Each of the current
      participants (12 naive and 12 trained in BCTTv1) was presented with a random
      sample of the written descriptions and asked to form groups of descriptions they
      judged to be describing the same intervention. For each participant, we assessed
      the number of groupings of BCI descriptions, their purity (containing only one
      BCI) and their differentiation (having a dominant BCI). RESULTS: All except one
      participant classified the descriptions into more than two groupings. Naive
      participants created significantly more groupings, fewer 'pure' groupings and
      less differentiated groupings (all Mann-Whitney p < .05). CONCLUSIONS: Written
      communications of BCI contents may not be recognised and interpreted adequately
      to support implementation. BCT taxonomy training may lead to some progress in
      interpreting the active content of interventions but, based on this limited
      study, further progress is needed if BCIs for accurate implementation.

PMID- 29019424
TI  - Endoscopy for patients affected by inflammatory bowel disease: bowel preparation
      and sedation.
AB  - INTRODUCTION: Endoscopy has a key role in the management of inflammatory bowel
      disease (IBD). It is helpful in the diagnosis, in case of relapse,
      refractoriness, before therapeutic changes, after surgery as well as in the
      assessment of mucosal healing and in the surveillance of colo-rectal cancer. IBD
      patients are intended to undergo several times the examination during their
      lifespan. Bowel preparation and sedation highly contribute to high-quality
      colonoscopy. Areas covered: Few studies addressed preparation and sedation in the
      field of IBD. In this review, we focused our attention on the available evidences
      about bowel preparation and sedation in patients with IBD. Expert commentary: In
      recent years, the goal of medical treatment in IBD is shifting from clinical
      improvement in symptoms towards mucosal healing. High-quality endoscopy will gain
      even more importance in the management of IBD. It is important to locate the most
      effective preparation and the best sedation in patient with IBD to perform a high
      quality endoscopy.

PMID- 29019426
TI  - Anti-catabolic neurohormonal blockade to improve skeletal muscle during disease.

PMID- 29019427
TI  - Management of inflammatory bowel disease-related anemia and iron deficiency with
      specific reference to the role of intravenous iron in current practice.
AB  - INTRODUCTION: Anemia is a common extraintestinal manifestation in patients with
      inflammatory bowel disease, impacting disease prognosis, morbidity,
      hospitalization rates and time lost from work. While iron deficiency anemia and
      anemia of chronic inflammation predominate, combinations of hematimetric and
      biochemical markers facilitate the diagnosis and targeted therapy of other
      etiologies according to their underlying pathophysiological causes. Intravenous
      iron replacement is currently recommended in IBD patients with moderate to severe
      anemia or intolerance to oral iron. Areas covered: This review examines the
      impact, pathophysiology and diagnostics of iron deficiency and anemia, compares
      the characteristics and safety profiles of available oral and intravenous iron
      preparations, and highlights issues which require consideration in decision
      making for therapy administration and monitoring. Expert opinion: Modern
      intravenous iron formulations have been shown to be safe and effective in IBD
      patients, allowing rapid anemia correction and repletion of iron stores. While
      traditional oral iron preparations are associated with increased inflammation,
      negative effects on the microbiome, and poor tolerance and compliance, first
      clinical trial data indicate that newer oral compounds such as ferric maltol and
      sucrosomial iron offer improved tolerability and may thus offer a viable
      alternative for the future.

PMID- 29019430
TI  - Conference Diary.

PMID- 29019428
TI  - Binding analysis of antioxidant polyphenols with PAMAM nanoparticles.
AB  - Dietary polyphenols are abundant micronutrients in our diet and paly major role
      in prevention of degenerative diseases. The binding efficacy of antioxidant
      polyphenols resveratrol, genistein, and curcumin with PAMAM-G3 and PAMAM-G4
      nanoparticles was investigated in aqueous solution at physiological conditions,
      using multiple spectroscopic methods, TEM images, and docking studies. The
      polyphenol bindings are via hydrophilic, hydrophobic, and H-bonding contacts with
      resveratrol forming more stable conjugates. As PAMAM size increased the loading
      efficacy and the stability of polyphenol-polymer conjugates were increased.
      Polyphenol binding induced major alterations of dendrimer morphology. PAMAM
      nanoparticles are capable of delivery of polyphenols in vitro.

PMID- 29019431
TI  - Synthesis and spectroscopic characterization study of new palladium complexes
      containing bioactive O,O-chelated ligands: evaluation of the DNA/protein BSA
      interaction, in vitro antitumoural activity and molecular docking.
AB  - [Pd{(C,N)-C6H4CH2NH(Et) (Qu)] (2) and [Pd{(C,N)-C6H4CH2NH(Et) (Nar)] (3) (Qu =
      Quercetin, Nar = Naringin) mononuclear palladium (II) complexes have been
      synthesized and characterized using elemental analysis, IR and electronic
      spectroscopy. The interaction of the prepared complexes with calf thymus DNA and
      bovine serum albumin (BSA), monitored by UV-visible and fluorescence titrations,
      respectively, have been carried out to better understand the mode of their action
      under biological conditions. Intercalative binding mode between the complexes and
      DNA is suggested by the binding constant (Kb) values of 2.5 * 106 and 3.2 * 106
      for complexes 2 and 3, respectively. In particular, the in vitro cytotoxicity of
      the complexes on two cancer cells lines (bladder carcinoma TCC and breast cancer
      MCF7) showed that the compounds had broad spectrum, anti-cancer activity with low
      IC50 values and the order of in vitro anticancer activities is consistent with
      the DNA-binding affinities. In the meantime, the quenching of tryptophan emission
      with the addition of complexes using BSA as a model protein indicated the protein
      binding ability. The quenching mechanisms of BSA by the complexes were static
      processes, according to the results obtained. The competitive binding using
      Warfarin, Digoxin and Ibuprofen site markers, which contain definite biding
      sites, demonstrated that the complexes bind to site I on BSA. Ultimately, the
      binding sites of DNA and BSA with the complexes have been determined by molecular
      modelling studies.

PMID- 29019432
TI  - Conference Diary.

PMID- 29019434
TI  - Session 3-Labour and Delivery.

PMID- 29019436
TI  - SESSION 1-FETAL MEDICINE.

PMID- 29019435
TI  - SESSION 2-MATERNAL MEDICINE.

PMID- 29019437
TI  - SESSION 3-LABOUR AND DELIVERY.

PMID- 29019438
TI  - Session 1-Fetal Medicine.

PMID- 29019440
TI  - Disclosure and Fit Capability of the Filtering Facepiece Respirator.
AB  - The filtering facepiece air-purifying respirator is annually purchased in the
      tens of millions and widely used for worker protection from harmful airborne
      particulates. The workplace consumers of this safety product, i.e., employers,
      workers, and safety and health professionals, have assurances of its
      effectiveness through the respirator certification and disclosure requirements of
      the National Institute for Occupational Safety and Health. However, the
      certification of a critical performance requirement has been missing for the
      approved filtering facepiece respirator since 1995: fit capability. Without this
      certification, consumers continue to be at risk of purchasing a respirator model
      that may fit a small percentage of the intended users. This commentary updates
      and expands an earlier one by this author, addresses the consequences of poorly
      fitting certified models on the market and lack of disclosure, and calls for
      further action by National Institute for Occupational Safety and Health to meet
      the needs and expectations of the consumer.

PMID- 29019439
TI  - Ibrutinib as salvage therapy in mantle cell lymphoma with central nervous system
      involvement in a pretreated unfit patient.

PMID- 29019441
TI  - Resilient, Responsive, and Healthy Developing Bones: The Good News About Exercise
      and Bone in Children and Youth.

PMID- 29019442
TI  - The Use of Hamstring Fatigue to Reduce Quadriceps Inhibition After Anterior
      Cruciate Ligament Reconstruction.
AB  - Arthrogenic muscle inhibition, an inability to fully activate the quadriceps
      muscles, has been persistently observed after anterior cruciate ligament
      reconstruction (ACLr) surgery. Reductions in quadriceps activation may be partly
      due to the flexion reflex pathway, hamstrings activation, and reciprocal
      quadriceps inhibition. Since central fatigue has been shown to modify hamstring
      excitability and change the hamstring reflex response, hamstring fatigue might
      alleviate quadriceps muscle inhibition by counteracting the flexion reflex. In
      this study, nine young adult athletes (age: M = 19.9 years, SD = 1.7) with
      unilateral ACLr and nine control athletes (age: M = 24.0 years, SD = 2.4) with no
      previous history of knee injury performed tempo squats to induce fatigue. The
      ACLr group tended to use hamstrings for more hip flexion and trunk forward
      flexion than the control group. We assessed each participant's quadriceps
      inhibition through the central activation ratio (CAR), measured by twitch
      interpolation, before and after the induced fatigue. A mixed analysis of variance
      was used to examine the effect of fatigue on the CAR between pre- and post
      fatigue and for both ACLr and control groups. The ACLr group showed significantly
      ( p = .010) greater CAR of the quadriceps post-fatigue ( M = 96.0%, SD = 7.6%)
      than pre-fatigue ( M = 81.2%, SD = 15.8%), while the control group showed no
      significant ( p = .969) pre-fatigue ( M = 96.9%, SD = 9.6%) and post-fatigue ( M
      = 97.0%, SD = 17.1%) differences. Thus, fatigue training may be used as a
      rehabilitation strategy to restore normal quadriceps function at the knee joint
      following ACL reconstruction by relaxing the hamstrings and overcoming quadriceps
      inhibition.

PMID- 29019443
TI  - Complexity and the human experience: modelling complexity in the humanities and
      social sciences.

PMID- 29019444
TI  - Evaluation of intraoperative analgesia provided by incisional lidocaine and
      bupivacaine in cats undergoing ovariohysterectomy.
AB  - Objectives The objective of this study was to assess the intraoperative analgesic
      effect of preoperative infiltration of the incision site with lidocaine or a
      mixture of lidocaine with bupivacaine in cats undergoing ovariohysterectomy
      (OHE). Methods This was a prospective, randomised clinical study. Healthy female
      intact cats (n = 75) undergoing OHE under medetomidine-ketamine-buprenorphine
      anaesthesia were assigned randomly into three treatment groups (n = 25 per group)
      to receive one of two local anaesthesia protocols or placebo preoperatively in
      the midline incision: lidocaine 1.5 mg/kg (group GL) or mixture of lidocaine 1
      mg/kg and bupivacaine 1 mg/kg (group GLB) or sodium chloride 0.9% (control
      group). Blood pressure, heart and respiratory rate, temperature, muscle tonus and
      pupillary reflex were registered during surgery. During recovery, the cats were
      observed for side effects. Postoperative analgesia was provided with meloxicam
      (0.2 mg/kg). Most cats were rechecked 2 weeks postoperatively to remove skin
      sutures. Results There was no significant difference between groups regarding
      breed, age, body weight, surgical time and postoperative complication rate. The
      majority of the cats (60%) included in the control group received a supplemental
      bolus of propofol during surgery, when compared with 43% and 44% of the cats
      included in the GL and GLB groups, respectively. Heart rate was significantly
      higher ( P <0.05) in the control group at the time of excision of the second
      ovary and the uterine body. Mean arterial pressure (MAP) was stable in both
      treatment groups; in contrast, it tended to increase in the control group. Heart
      rate and MAP were similar between treatment groups. Conclusions and relevance
      Preoperative incisional block with only lidocaine or combined with bupivacaine
      seems to produce a similar intraoperative analgesia in cats undergoing OHE.
      Despite the similar intraoperative analgesic effect between treatment groups, the
      combination of lidocaine and bupivacaine reduced the required doses, and had a
      faster onset of action and prolonged effect.

PMID- 29019445
TI  - The beneficial effect of contextual emotion on memory: the role of integration.
AB  - This study investigates the effects of emotion on the integration mechanism which
      binds together the components of an event and the relations between these
      components and encodes them within a memory trace [Versace, R., Vallet, G. T.,
      Riou, B., Lesourd, M., Labeye, E, & Brunel, L. (2014). Act-In: An integrated view
      of memory mechanisms. Journal of Cognitive Psychology, 26(3), 280-306. doi:
      10.1080/20445911.2014.892113 ]. Based on the literature, the authors argue that,
      in a memory task, contextual emotion could strengthen the integration mechanism
      and, more specifically, the relations between a target item and its contextual
      features. To test this hypothesis, the authors used two odorants (neutral and
      negative) to compare the effects of a negative context with those of a neutral
      one on three different types of recall: item recall (memory for pictures
      objects), source recall (spatial position of the pictures in a matrix) and recall
      of the association between an item and its location. The results showed that, in
      the negative odour context, association recall and source recall - but not item
      recall - were better than in the neutral odour context thus confirming the effect
      of emotion on integration. The results lead to the hypothesis that the effects of
      emotion on memory are linked to the way emotion is introduced into the
      experimental settings: via the items to be memorised or via the context.

PMID- 29019446
TI  - The role of the oximes HI-6 and HS-6 inside human acetylcholinesterase inhibited
      with nerve agents: a computational study.
AB  - The oximes 4-carbamoyl-1-[({2-[(E)-(hydroxyimino) methyl] pyridinium-1-yl}
      methoxy) methyl] pyridinium (known as HI-6) and 3-carbamoyl-1-[({2-[(E)
      (hydroxyimino) methyl] pyridinium-1-yl} methoxy) methyl] pyridinium (known as HS
      6) are isomers differing from each other only by the position of the carbamoyl
      group on the pyridine ring. However, this slight difference was verified to be
      responsible for big differences in the percentual of reactivation of
      acetylcholinesterase (AChE) inhibited by the nerve agents tabun, sarin,
      cyclosarin, and VX. In order to try to find out the reason for this, a
      computational study involving molecular docking, molecular dynamics, and binding
      energies calculations, was performed on the binding modes of HI-6 and HS-6 on
      human AChE (HssAChE) inhibited by those nerve agents.

PMID- 29019448
TI  - Comparison of ultrasonographic findings in cats with and without azotaemia.
AB  - Objectives The objective of this study was to identify the renal ultrasonographic
      (US) findings most strongly associated with azotaemia in cats. Methods US
      findings in 238 cats with (serum creatinine >180 MUmol/l) and 270 cats without
      azotaemia were compared in a retrospective case-control study. Cats with pre
      renal azotaemia or urethral obstruction were excluded. Data extracted from the
      medical records included age, body weight and body condition score (BCS).
      Quantitative and subjective US findings were extracted from archived ultrasound
      images and contemporaneous reports. Results In non-azotaemic cats, mean +/- SD
      renal length was 40.1 +/- 5.5 mm. Male cats had larger kidneys than female cats
      (mean difference 5.2 mm; P = 0.001) and, on average, the right kidney was
      slightly larger than the left (mean difference 1.6 mm; P = 0.01). Azotaemic cats
      had significantly lower mean body weight and BCS, and greater mean age and renal
      pelvic diameter. Renal pelvic diameter was negatively correlated with urine
      specific gravity (rho -0.44, P <0.001). Compared with non-azotaemic cats, there
      was no difference in mean renal length of azotaemic cats because the numbers with
      enlarged kidneys and small kidneys were similar. Radiologists' subjective
      assessments of renal size differed markedly between azotaemic and non-azotaemic
      cats, with azotaemic cats more likely to be recorded falsely as having abnormally
      small or enlarged kidneys. US findings significantly associated with azotaemia
      were perinephric fluid (odds ratio [OR] 26.4, 95% confidence interval [CI] 3.4
      207.7), small kidneys (OR 8.4, 95% CI 4.0-17.4), hyperechoic renal cortex (OR
      4.1, 95% CI 2.2-7.6), loss of corticomedullary differentiation (OR 4.1, 95% CI
      1.8-9.6), renal calculi (OR 2.7, 95% CI 1.4-4.9), enlarged kidneys (OR 2.5, 95%
      CI 1.2-5.5) and dilated renal pelvis (OR 1.6, 95% CI 1.3-1.9). Conclusions and
      relevance Perinephric fluid was the US finding most strongly associated with
      azotaemia in this study and may merit more emphasis than it has received to date.
      Bias in radiologists' subjective assessments of renal size suggests that other
      subjective findings will also be biased.

PMID- 29019447
TI  - Survival of patients with CD20-negative variants of large B-cell lymphoma: an
      analysis of the National Cancer Data Base.
AB  - Using records from the National Cancer Data Base, we studied overall survival of
      CD20-negative variants of diffuse large B-cell lymphoma (DLBCL): primary effusion
      (PEL, N = 228), plasmablastic (PBL, N = 481), ALK-positive large B-cell (ALK +
      LBLC, N = 15), and human herpesvirus-8-positive DLBCL (HHV8 + DLBCL, N = 77).
      Three-year survival was 27% for PEL, 40% for PBL, 34% for ALK + LBCL, and 63% for
      HHV8 + DLBCL. Compared with unspecified DLBCL, and adjusting for clinical
      characteristics (including the HIV status), survival was significantly worse for
      PEL (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.31-1.90), PBL (HR
      1.66; 95% CI, 1.41-1.95), and ALK + LBCL (HR, 2.70; 95% CI, 1.27-5.75), but not
      for HHV8 + DLBCL (HR, 0.89; 95% CI, 0.54-1.45). The HIV status was not an
      independent prognostic factor in PEL, PBL, or HHV8 + DLBCL. Advanced stage was
      prognostic for PBL (p = .0002), but not for ALK + LBCL (p = .96), or HHV8 + DLBCL
      (p = .28). In PEL and PBL survival significantly differed according to primary
      site. Novel therapeutic approaches are urgently needed for these rare diseases.

PMID- 29019449
TI  - Middle Meningeal Artery Embolization for Chronic Subdural Hematoma.
AB  - Purpose To evaluate the effect of middle meningeal artery (MMA) embolization on
      chronic subdural hematoma (CSDH) and compare the treatment outcomes of MMA
      embolization and conventional treatment. Materials and Methods All consecutive
      patients 20 years or older with CSDH were assessed for eligibility. CSDHs with a
      focal location, a thickness of 10 mm or less, no mass effect, or underlying
      conditions were excluded. Seventy-two prospectively enrolled patients with CSDH
      underwent MMA embolization (embolization group; as the sole treatment in 27
      [37.5%] asymptomatic patients and with additional hematoma removal for symptom
      relief in 45 [62.5%] symptomatic patients). For comparison, 469 patients who
      underwent conventional treatment were included as a historical control group
      (conventional treatment group; close, nonsurgical follow-up in 67 [14.3%] and
      hematoma removal in 402 [85.7%] patients). Primary outcome was treatment failure
      defined as a composite of incomplete hematoma resolution (remaining or
      reaccumulated hematoma with thickness > 10 mm) or surgical rescue (hematoma
      removal for relief of symptoms that developed with continuous growth of initial
      or reaccumulated hematoma). Secondary outcomes included surgical rescue as a
      component of the primary outcome and treatment-related complication for safety
      measure. Six-month outcomes were compared between the study groups with logistic
      regression analysis. Results Spontaneous hematoma resolution was achieved in all
      of 27 asymptomatic patients undergoing embolization without direct hematoma
      removal. Hematoma reaccumulation occurred in one (2.2%) of 45 symptomatic
      patients receiving embolization with additional hematoma removal. Treatment
      failure rate in the embolization group was lower than in the conventional
      treatment group (one of 72 patients [1.4%] vs 129 of 469 patients [27.5%],
      respectively; adjusted odds ratio [OR], 0.056; 95% confidence interval [CI]:
      0.011, 0.286; P = .001). Surgical rescue was less frequent in the embolization
      group (one of 72 patients [1.4%] vs 88 of 469 patients [18.8%]; adjusted OR,
      0.094; 95% CI: 0.018, 0.488; P = .005). Treatment-related complication rate was
      not different between the two groups (0 of 72 patients vs 20 of 469 patients
      [4.3%]; adjusted OR, 0.145; 95% CI: 0.009, 2.469; P = .182). Conclusion MMA
      embolization has a positive therapeutic effect on CSDH and is more effective than
      conventional treatment. (c) RSNA, 2017.

PMID- 29019450
TI  - Cataract Risk in a Cohort of U.S. Radiologic Technologists Performing Nuclear
      Medicine Procedures.
AB  - Purpose To estimate the risk of cataract in a cohort of nuclear medicine (NM)
      radiologic technologists on the basis of their work histories and radiation
      protection practices. Materials and Methods In the years 2003-2005 and 2012-2013,
      42 545 radiologic technologists from a U.S. prospective study completed
      questionnaires in which they provided information regarding their work histories
      and cataract histories. Cox proportional hazards models, stratified according to
      birth-year cohort (born before 1940 or born in 1940 or later) and adjusted for
      age, sex, and race, were used to estimate hazard ratios (HRs) for the risk of
      cataract in radiologic technologists according to NM work history practices
      according to decade. Results During the follow-up period (mean follow-up, 71/2
      years), 7137 incident cataracts were reported. A significantly increased risk of
      cataract (HR, 1.08; 95% confidence interval [CI]: 1.03, 1.14) was observed among
      workers who performed an NM procedure at least once-as opposed to never. Risks of
      cataract were increased in the group who had performed a diagnostic (HR, 1.07;
      95% CI: 1.01, 1.12) or therapeutic (HR, 1.10; 95% CI: 1.04, 1.17) NM procedure.
      Risks were higher for those who had first performed diagnostic NM procedures in
      the 1980s to early 2000s (HR, 1.30; 95% CI: 1.08, 1.58) and those who had
      performed therapeutic NM procedures in the 1970s (HR, 1.11; 95% CI: 1.01, 1.23)
      and in the 1980s to early 2000s (HR, 1.14; 95% CI: 1.02, 1.29). With the
      exception of a significantly increased risk associated with performing
      therapeutic NM procedures without shielding the radiation source in the 1980s
      (HR, 1.32; 95% CI: 1.04, 1.67), analyses revealed no association between cataract
      risk and specific radiation protection technique used. Conclusion An increased
      risk of cataract was observed among U.S. radiologic technologists who had
      performed an NM procedure at least once. This association should be examined in
      future studies incorporating estimated lens doses. (c) RSNA, 2017.

PMID- 29019451
TI  - Autoimmunity in a cohort of 471 patients with primary antibody deficiencies.
AB  - OBJECTIVES: The aim of this study was to evaluate the frequency of autoimmunity
      in primary antibody deficiency (PAD). METHODS: A total of 471 patients with PADs
      enrolled in this retrospective cohort study. For all patients' demographic
      information, clinical records and laboratory data were collected to investigate
      autoimmune complications. RESULTS: Autoimmune disorders as the first presentation
      of immunodeficiency were recorded in 11 patients (2.5%). History of autoimmunity
      was recorded in 125 patients during the course of the disease (26.5%). The
      frequency of autoimmunity in common variable immune deficiency (32.0%) was higher
      than other forms of PADs. The most common autoimmune manifestations were reported
      to be autoimmune gastrointestinal disease and autoimmune cytopenias. Among
      patients with autoimmunity, 87 patients (69.6%) had a history of one autoimmune
      disorder, while 38 patients (30.4%) had a history of multiple autoimmunities. The
      immune thrombocytopenic purpura and autoimmune hemolytic anemia were the most two
      concomitant autoimmune disorders in 16 (42.1%) of 38 patients with multiple
      autoimmunities. Comparing the frequency of Tregs in PAD patients with
      autoimmunity showed that, patients with multiple autoimmunities had lower Tregs
      than those with single autoimmunity (p = 0.017). CONCLUSION: It is important that
      non-immunologist physicians be alert of the associated autoimmunity with PADs in
      order to reduce the diagnostic delay and establish timely immunoglobulin
      replacement therapy in these patients.

PMID- 29019453
TI  - EgoNet identifies differential ego-modules and pathways related to prednisolone
      resistance in childhood acute lymphoblastic leukemia.
AB  - PURPOSE: To extract feature ego-modules and pathways in childhood acute
      lymphoblastic leukemia (ALL) resistant to prednisolone treatment, and further to
      explore the mechanisms behind prednisolone resistance. MATERIALS AND METHODS:
      EgoNet algorithm was used to identify candidate ego-network modules, mainly via
      constructing differential co-expression network (DCN); selecting ego genes;
      collecting ego-network modules; refining candidate modules. Afterwards,
      statistical significance was calculated for these candidate modules. Biological
      functions of differential ego-network modules were identified using Reactome
      database. To verify this proposed method can lead to truly positive findings in
      clinical settings, support vector machine (SVM) was utilized to compute the AUC
      values for each significant pathway using 3-fold cross-validation method. To
      predict the reliability of our findings, another established method (attract) was
      used to identify the differential attractor modules using the same microarray
      profile. RESULTS: After eliminating the modules with classification accuracy <
      0.9 and node number < 15, only ego-network module 30 was eligible. After
      significance calculation, module 30 was significant. Module 30 was enriched in
      APC/C-mediated degradation of cell cycle proteins. The AUC for the significant
      pathway of APC/C-mediated degradation of cell cycle proteins was 0.915. Although
      the attract method obtained more modules, the module identified by our proposed
      method owned more gene nodes, and had more classification ability (AUC = 0.915).
      CONCLUSION: One differential ego-network module identified in childhood ALL
      resistance to prednisolone based on DCN and EgoNet, might be helpful to reveal
      the mechanisms underlying prednisolone resistance in childhood ALL.

PMID- 29019454
TI  - The Dance of "Old" and "New" in Chinese Print Culture, 1860s-1955.
AB  - Argument Scholars of modern Chinese publishing and book culture focus on the
      dramatic transformations that took place in the late nineteenth and early
      twentieth centuries: the new technologies that enabled "mass" printing and the
      development of "modern" genres of print. They often neglect the fact that
      xylography remained a working technology through much of the Republican period
      and even into the People's Republic of China. Here I examine the continued use of
      woodblock printing and the continuing popularity of "traditional" textual genres
      from two perspectives. First, from a "bottom up" perspective, I examine the
      production and sale of woodblock texts in rural markets, often in the face of
      efforts by both the Republic and the People's Republic to prohibit their use.
      Second, from a perspective from the top, I consider the deliberate choices made
      by the government, some elite book collector-publishers, and Daoist and Buddhist
      devotees to print certain works xylographically.

PMID- 29019452
TI  - Minimal residual disease analysis in myeloma - when, why and where.
AB  - The primary hurdle in the path to curing multiple myeloma (MM) is defining a
      validated minimal residual disease (MRD) and its utility in the therapeutic
      decision making. A better definition of MRD will aid in tailoring MM therapy
      further to address the clonal heterogeneity and genomic instability and overcome
      patient's ineffective immune surveillance. MRD analysis can define the logical
      endpoint for maintenance therapy, in addition also aids in providing a better
      clinical end point for studies comparing novel agents in myeloma. MRD is a
      surrogate for the survival in MM. Guidelines for global incorporation of MRD in
      myeloma are fraught with lack of standardization, universal availability and
      abridged physicians' understanding of MRD modalities. We aimed at addressing some
      of the frequently asked questions in the MRD assessment and will also place in
      perspective some arguments in favor of MRD assessment in routine practice and
      clinical trial scenario.

PMID- 29019455
TI  - "To Feel at Home in the Wonderful World of Modern Science": New Chinese
      Historiography and Qing Intellectual History.
AB  - Argument In recent decades a large body of scholarship on the first half of
      twentieth-century China has successfully shown the ways in which history and
      historiography had been constructed at the time, as well as the links between
      history, national identity, education, and politics that was forged during this
      period. In this paper, I examine Qing intellectual history, in particular that of
      the mid or "High Qing." I discuss the development of the historiography of this
      field in the early twentieth century by drawing on the larger developments in
      historiography; by demonstrating how these developments had shaped Qing
      intellectual history for later times; by focusing on the historical actors' sense
      of the importance of "science," being "scientific," and "modernization"; and, by
      unraveling the intimate connections to older historiographical narratives going
      back all the way to the eighteenth and nineteenth centuries.

PMID- 29019456
TI  - Introduction: Paving the Old-New Way from Qing to China.
AB  - The funeral procession of Sheng Xuanhuai (, 1844-1916) - the renowned Qing
      scholar-official, financier, and "father of Chinese industrialism" - meandered
      through the streets of Shanghai on 18 November 1917. The funeral was a grand
      event, one that was purportedly documented in film, later to be distributed as
      the first "news short-film" () in China. The North China Herald reported on the
      event in some detail, at times in rather florid language, and suggested that "the
      cortege was splendid and impressive, bringing back the days of the Manchu
      emperors. The ceremonial costumes, the musical instruments and much more of the
      accoutrements dated back to the days of the Empire" ("Sheng Kung-pao's Funeral,"
      1917, 467-68). And indeed, the procession included a variety of ritual customs
      and insignia from Qing (1644-1911) times: imperial banners, ancestral tablets,
      Buddhist and Daoist priests, paper artifacts, and much more. Simultaneously,
      nonetheless, other kinds of participants and objects - new and not of imperial
      pedigree - were part of and intermixed with the older materials: certificates of
      rank were carried on cars; boy scouts and college students marched alongside the
      priests; many of the participants arrived by train (mainly from Sheng's hometown,
      Suzhou); and as the Shanghai portion of the procession ended, it continued by
      steamer to Suzhou. The conclusion of the North China Herald account, however,
      seems to have emphasized a dichotomy of old and new rather than a joyful mix of
      the two: Hundreds of men, dressed in the ancient costume of the old dynasties,
      bore a strong contrast to the eight behind them, sons of intimate friends of the
      deceased. They were on horseback and wore high silk hats, frock coats and white
      breeches tucked in riding boots. Truly the passing of the old and the entering of
      the new. (Ibid.; emphasis added) This view - the old giving way to the new - was
      not just an off-hand (Western) journalistic analysis; it was part of a larger
      discourse about the nature of modernity, about progress, and about the
      relationship between East and West. By the early twentieth century, China was
      often perceived by most Westerners and Chinese alike as traditional, backward,
      and weak. It was, thus, commonly stated that the old was giving way to the new
      (descriptive), should be giving way to the new (prescriptive), or was bound to
      give way to the new (quasi-fatalistic), if China was to survive. This kind of
      discourse was put forward by both Western and Chinese writers, who embraced this
      linear, progressive, view of the relationship between the old and the new, well
      before Sheng's funeral or the Qing's demise. In the aftermath of that demise, the
      New (not "Modern") Culture Movement began to grow and seek solutions for the old
      new nation's crisis. The Movement's rhetoric in particular advanced the need for
      the triumph of the new, and journals, such as New People, New Tide, or New Youth
      (, , ) served as media for extending such views.

PMID- 29019457
TI  - Science for the Chinese Common Reader? Myriad Treasures and New Knowledge at the
      Turn of the Twentieth Century.
AB  - Argument This article argues that in order to discern the place of science in the
      epistemology of Chinese common readers, it is critical to look beyond the coastal
      enclaves where foreign missionaries and experts interacted with Chinese scholars
      and officials, beyond the translated treatises they produced, and even beyond the
      various forms of new media that attempted to more widely disseminate the
      principles of Western science. Instead, it asserts the need to engage a different
      register of materials that were less directly tied to foreign expertise, more
      directly in line with pre-existing lineages of printed materials, and at the same
      time, integral to early-twentieth-century Chinese circuits of information. The
      article focuses explicitly on one print phenomena that has been completely
      overlooked in the scholarship to date, the expansion and revitalization of the
      genre of texts known as wanbao quanshu (comprehensive compendia of myriad
      treasures) in the late Qing (1890-1911) and early Republic (1912-1930).

PMID- 29019458
TI  - Visualizing the Geography of the Diseases of China: Western Disease Maps from
      Analytical Tools to Tools of Empire, Sovereignty, and Public Health Propaganda,
      1878-1929.
AB  - Argument This article analyzes for the first time the earliest western maps of
      diseases in China spanning fifty years from the late 1870s to the end of the
      1920s. The 24 featured disease maps present a visual history of the major
      transformations in modern medicine from medical geography to laboratory medicine
      wrought on Chinese soil. These medical transformations occurred within new
      political formations from the Qing dynasty (1644-1911) to colonialism in East
      Asia (Hong Kong, Taiwan, Manchuria, Korea) and hypercolonialism within China
      (Tianjin, Shanghai, Amoy) as well as the new Republican Chinese nation state
      (1912-49). As a subgenre of persuasive graphics, physicians marshaled disease
      maps for various rhetorical functions within these different political contexts.
      Disease maps in China changed from being mostly analytical tools to functioning
      as tools of empire, national sovereignty, and public health propaganda
      legitimating new medical concepts, public health interventions, and political
      structures governing over human and non-human populations.

PMID- 29019459
TI  - Self-Inflicated Cardiac Injury by Multiple Sewing Needles.

PMID- 29019462
TI  - Stability and electronic properties of hybrid SnO bilayers: SnO/graphene and
      SnO/BN.
AB  - Van der Waals structures based on two-dimensional materials have been considered
      as promising structures for novel nanoscale electronic devices. Two-dimensional
      SnO films which display intrinsic p-type semiconducting properties were
      fabricated recently. In this paper, we consider vertically stacked
      heterostructures consisting of a SnO monolayer with graphene or a BN monolayer to
      investigate their stability, electronic and transport properties using density
      functional theory. The calculated results find that the properties of the
      constituent monolayers are retained in these SnO-based heterostructures, and a p
      type Schottky barrier is formed in the SnO/graphene heterostructure.
      Additionally, the Schottky barrier can be effectively controlled with an external
      electric field, which is useful characteristic for the van der Waals
      heterostructure-based electronic devices. In the SnO/BN heterostructure, the
      electronic properties of SnO are least affected by the insulating monolayer
      suggesting that the BN monolayer would be an ideal substrate for SnO-based
      nanoscale devices.

PMID- 29019460
TI  - Auditory Hallucinations as Translational Psychiatry: Evidence from Magnetic
      Resonance Imaging.
AB  - In this invited review article, I present a translational perspective and
      overview of our research on auditory hallucinations in schizophrenia at the
      University of Bergen, Norway, with a focus on the neuronal mechanisms underlying
      the phenomenology of experiencing "hearing voices". An auditory verbal
      hallucination (i.e. hearing a voice) is defined as a sensory experience in the
      absence of a corresponding external sensory source that could explain the
      phenomenological experience. I suggest a general frame or scheme for the study of
      auditory verbal hallucinations, called Levels of Explanation. Using a Levels of
      Explanation approach, mental phenomena can be described and explained at
      different levels (cultural, clinical, cognitive, brain-imaging, cellular and
      molecular). Another way of saying this is that, to advance knowledge in a
      research field, it is not only necessary to replicate findings, but also to show
      how evidence obtained with one method, and at one level of explanation, converges
      with evidence obtained with another method at another level. To achieve
      breakthroughs in our understanding of auditory verbal hallucinations, we have to
      advance vertically through the various levels, rather than the more common
      approach of staying at our favourite level and advancing horizontally (e.g., more
      advanced techniques and data acquisition analyses). The horizontal expansion
      will, however, not advance a deeper understanding of how an auditory verbal
      hallucination spontaneously starts and stops. Finally, I present data from the
      clinical, cognitive, brain-imaging, and cellular levels, where data from one
      level validate and support data at another level, called converging of evidence.
      Using a translational approach, the current status of auditory verbal
      hallucinations is that they implicate speech perception areas in the left
      temporal lobe, impairing perception of and attention to external sounds.
      Preliminary results also show that amygdala is implicated in the emotional
      "colouring" of the voices and that excitatory neurotransmitters might be
      involved. What we do not know is why hallucinatory episodes occur spontaneously,
      why they fluctuate over time, and what makes them spontaneously stop. Moreover,
      is voice hearing a category or dimension in its own right, independent of
      diagnosis, and why is the auditory modality predominantly implicated in psychotic
      disorders, while the visual modality dominates in, for example, neurological
      diseases?

PMID- 29019463
TI  - Size-dependent melting modes and behaviors of Ag nanoparticles: a molecular
      dynamics study.
AB  - The size-dependent melting behaviors and mechanisms of Ag nanoparticles (NPs)
      with diameters of 3.5-16 nm were investigated by molecular dynamics (MD). Two
      distinct melting modes, non-premelting and premelting with transition ranges of
      about 7-8 nm, for Ag NPs were demonstrated via the evolution of distribution and
      transition of atomic physical states during annealing. The small Ag NPs (3.5-7
      nm) melt abruptly without a stable liquid shell before the melting point, which
      is characterized as non-premelting. A solid-solid crystal transformation is
      conducted through the migration of adatoms on the surface of Ag NPs with
      diameters of 3.5-6 nm before the initial melting, which is mainly responsible for
      slightly increasing the melting point of Ag NPs. On the other hand, surface
      premelting of Ag NPs with diameters of 8-16 nm propagates from the outer shell to
      the inner core with initial anisotropy and late isotropy as the temperature
      increases, and the close-packed facets {111} melt by a side-consumed way which is
      responsible for facets {111} melting in advance relative to the crystallographic
      plane {111}. Once a stable liquid shell is formed, its size-independent minimum
      thickness is obtained, and a three-layer structure of atomic physical states is
      set up. Lastly, the theory of point defect-pair (vacancy-interstitial) severing
      as the mechanism of formation and movement of the solid-liquid interface was also
      confirmed. Our study provides a basic understanding and theoretical guidance for
      the research, production and application of Ag NPs.

PMID- 29019464
TI  - Ovipositor-inspired steerable needle: design and preliminary experimental
      evaluation.
AB  - Flexible steerable needles have the potential to allow surgeons to reach deep
      targets inside the human body with higher accuracy than rigid needles do.
      Furthermore, by maneuvering around critical anatomical structures, steerable
      needles could limit the risk of tissue damage. However, the design of a thin
      needle (e.g. diameter under 2 mm) with a multi-direction steering mechanism is
      challenging. The goal of this paper is to outline the design and experimental
      evaluation of a biologically inspired needle with a diameter under 2 mm that
      advances through straight and curved trajectories in a soft substrate without
      being pushed, without buckling, and without the need of axial rotation. The
      needle design, inspired by the ovipositor of parasitoid wasps, consisted of seven
      nickel titanium wires and had a total diameter of 1.2 mm. The motion of the
      needle was tested in gelatin phantoms. Forward motion of the needle was evaluated
      based on the lag between the actual and the desired insertion depth of the
      needle. Steering was evaluated based on the radius of curvature of a circle
      fitted to the needle centerline and on the ratio of the needle deflection from
      the straight path to the insertion depth. The needle moved forward inside the
      gelatin with a lag of 0.21 (single wire actuation) and 0.34 (double wire
      actuation) and achieved a maximum curvature of 0.0184 cm-1and a deflection-to
      insertion ratio of 0.0778. The proposed biologically inspired needle design is a
      relevant step towards the development of thin needles for percutaneous
      interventions.

PMID- 29019461
TI  - Translational Functional Neuroimaging in the Explanation of Depression.
AB  - Translation as a notion and procedure is deeply embodied in medical science and
      education. Translation includes the possibility to translate data across
      disciplines to improve diagnosis and treatment procedures. The evidence
      accumulated using translation serves as a vehicle for reification of medical
      diagnoses. There are promising, established post hoc correlations between the
      different types of clinical tools (interviews and inventories) and neuroscience.
      The various measures represent statistical correlations that must now be
      integrated into diagnostic standards and procedures but this, as a whole, is a
      step forward towards a better understanding of the mechanisms underlying
      psychopathology in general and depression in particular. Here, we focus on
      functional magnetic resonance imaging studies using a trans-disciplinary approach
      and attempt to establish bridges between the different fields. We will
      selectively highlight research areas such as imaging genetics, imaging immunology
      and multimodal imaging, as related to the diagnosis and management of depression.

PMID- 29019465
TI  - Facile and controllable electrochemical fabrication of cell-adhesive polypyrrole
      electrodes using pyrrole-RGD peptides.
AB  - Electrically conductive polymers, such as polypyrrole (PPy), have been widely
      used for the fabrication of various biosensors and tissue engineering scaffolds.
      For their biologically relevant applications, conductive biomaterials capable of
      intimate cellular interactions are highly desired. However, conventional methods
      to incorporate biomolecules into conductive polymers do not offer fine and easy
      control over the surface density of the biomolecules and/or their stability. We
      present a novel method to electrochemically immobilize cell-adhesive Arg-Gly-Asp
      (RGD) ligands on PPy electrode surfaces with a simple control over the peptide
      surface density by varying the electrodeposition time. Synthesized pyrrole
      GGGRGDS conjugates were electrochemically incorporated onto the surfaces of PPy
      coated electrodes. The electrochemical impedances of the RGD-grafted PPy
      electrodes were not significantly different from the unmodified PPy films. Time
      of-flight secondary-ion mass spectroscopy confirmed the presence of the RGD motif
      on the surface of the modified electrodes. In vitro studies with human
      mesenchymal stem cells (hMSCs) showed higher adhesion and faster proliferation of
      hMSCs on the PPy with a higher RGD density. This facile electrochemical
      modification of electrode surfaces allowed for a good control over the peptide
      surface density and cellular interactions and will benefit the fabrication of
      cell-interactive scaffolds or bio-electrodes.

PMID- 29019466
TI  - Facile, one-pot and scalable synthesis of highly emissive aqueous-based
      Ag,Ni:ZnCdS/ZnS core/shell quantum dots with high chemical and optical stability.
AB  - We report here on a one-pot, mild and low cost aqueous-based synthetic route for
      the preparation of colloidally stable and highly luminescent dual-doped
      Ag,Ni:ZnCdS/ZnS core/shell quantum dots (QDs). The pure dopant emission of the Ni
      doped core/shell QDs was found to be highly affected by the presence of a second
      dopant ion (Ag+). Results showed that the PL emission intensity increases while
      its peak position experiences an obvious blue shift with an increase in the
      content of Ag+ ions. Regarding the optical observations, we provide a simple
      scheme for absorption-recombination processes of the carriers through impurity
      centers. To obtain optimum conditions with a better emission characteristic, we
      also study the effect of different reaction parameters, such as refluxing
      temperature, the pH of the core and shell solution, molar ratio of the dopant
      ions (Ni:(Zn+Cd) and Ag:(Zn+Cd)), and concentration of the core and shell
      precursors. Nonetheless, the most effective parameter is the presence of the ZnS
      shell in a suitable amount to eliminate surface trap states and enhance their
      emission intensity. It can also improve the bio-compatibility of the prepared QDs
      by restricting the Cd2+ toxic ions inside the core of the QDs. The present
      suggested route also revealed the remarkable optical and chemical stability of
      the colloidal QDs which establishes them as a decent kind of nano-scale structure
      for light emitting applications, especially in biological technologies. The
      suggested process also has the potential to be scaled-up while maintaining the
      emission characteristics and structural quality necessary for industrial
      applications in optoelectronic devices.

PMID- 29019467
TI  - Online adaptive neural control of a robotic lower limb prosthesis.
AB  - OBJECTIVE: The purpose of this study was to develop and evaluate an adaptive
      intent recognition algorithm that continuously learns to incorporate a lower limb
      amputee's neural information (acquired via electromyography (EMG)) as they
      ambulate with a robotic leg prosthesis. APPROACH: We present a powered lower limb
      prosthesis that was configured to acquire the user's neural information and
      kinetic/kinematic information from embedded mechanical sensors, and identify and
      respond to the user's intent. We conducted an experiment with eight transfemoral
      amputees over multiple days. EMG and mechanical sensor data were collected while
      subjects using a powered knee/ankle prosthesis completed various ambulation
      activities such as walking on level ground, stairs, and ramps. Our adaptive
      intent recognition algorithm automatically transitioned the prosthesis into the
      different locomotion modes and continuously updated the user's model of neural
      data during ambulation. MAIN RESULTS: Our proposed algorithm accurately and
      consistently identified the user's intent over multiple days, despite changing
      neural signals. The algorithm incorporated 96.31% [0.91%] (mean, [standard
      error]) of neural information across multiple experimental sessions, and
      outperformed non-adaptive versions of our algorithm-with a 6.66% [3.16%] relative
      decrease in error rate. SIGNIFICANCE: This study demonstrates that our adaptive
      intent recognition algorithm enables incorporation of neural information over
      long periods of use, allowing assistive robotic devices to accurately respond to
      the user's intent with low error rates.

PMID- 29019468
TI  - Silver and gold nanoparticles in nanometric confined templates: synthesis and
      alloying within the anisotropic pores of oblique angle deposited films.
AB  - In this work we have developed an infiltration methodology to incorporate metal
      nanoparticles (NPs) of controlled size and shape into the open voids available in
      oblique angle deposited thin films. These NPs exhibited well-defined surface
      plasmon resonances (SPRs). The nanometric confined space provided by their porous
      microstructure has been used as a template for the growth of anisotropic NPs with
      interesting SPR properties. The fabrication methodology has been applied for the
      preparation of films with embedded Ag and Au NPs with two associated plasmon
      resonance features that developed a dichroic behaviour when examined with
      linearly polarized light. A confined alloying process was induced by near IR
      nanosecond laser irradiation yielding bimetallic NPs with SPR features covering a
      large zone of the electromagnetic spectrum. The possibilities of the method for
      the tailored fabrication of a wide range colour palette based on SPR features are
      highlighted.

PMID- 29019469
TI  - Genetic origin, admixture and population history of aurochs (Bos primigenius) and
      primitive European cattle.
AB  - This corrects the article DOI: 10.1038/hdy.2016.79.

PMID- 29019470
TI  - Progress in the management of neonatal sepsis: the importance of a consensus
      definition.

PMID- 29019473
TI  - Systematic Mapping of Pressure Pain Thresholds of the Masseter and Temporalis
      Muscles and Assessment of Their Diversity Through the Novel Application of
      Entropy.
AB  - AIMS: To assess the diversity of pressure pain thresholds (PPTs) within the
      masseter and temporalis muscles by using the novel concept of entropy and to
      assess the differences in PPT scores between different sites of the masseter and
      temporalis muscles. METHODS: In this randomized, single-blinded study, the left
      and right masseter and temporalis muscles of 14 healthy volunteers were divided
      into 15 sites each, and the PPT was assessed for each of these sites. PPT
      assessments were performed in two different sessions. Entropy and center of
      gravity (COG) values were calculated for the PPTs of each muscle. Repeated
      measures analysis of variance was used to assess differences between muscles,
      sides, and sites for PPT, entropy, and COG scores. RESULTS: The main findings
      were: (1) PPT scores varied significantly between the masseter and temporalis
      muscles and within each of these muscles; (2) entropy values of PPT scores were
      not different between the masseter and temporalis muscles; and (3) COG values of
      PPT scores varied statistically, but these changes do not seem to be clinically
      relevant. CONCLUSION: The results of this study suggest that the anatomical
      layout of the masseter and temporalis muscles has implications for mechanical
      pain sensitivity and that areas have different sensitivities within these
      muscles. Furthermore, reference values for the entropy of PPTs in healthy
      individuals have been estimated, and comparing these values with those of
      patients with muscle-related pain conditions can provide quantitative information
      about the spatial heterogeneity of mechanical pain sensitivity, which may be a
      valuable clinical outcome measure.

PMID- 29019471
TI  - Infantile hemangioma: factors causing recurrence after propranolol treatment.
AB  - BackgroundPropranolol is the first-choice treatment for severe infantile
      hemangioma (IH). However, 10- 30% of lesions relapse after propranolol treatment.
      The mechanisms underlying IH recurrence after propranolol treatment have not been
      completely elucidated.MethodsThis study combined an examination of hemodynamic
      changes with research regarding hemangioma stem cells (hscs) with differentially
      expressed microRNAs (miRNAs) to identify the factors affecting IH recurrence
      after propranolol treatment. Hemodynamic changes were monitored in 21 recurrent
      cases using high-frequency color Doppler ultrasound, and hscs were treated with
      different concentrations of propranolol. The levels of differentially expressed
      miRNAs and the activity of related pathways were then compared between 18
      recurrent and 20 non-recurrent IH cases.ResultsDuring treatment, lesion depth and
      vessel density decreased, and the lesion resistance index increased. Obvious
      lesions and vessel signals were observed in recurrent cases compared with non
      recurrent cases. Propranolol effectively inhibited hscs proliferation. Twenty-two
      differentially expressed miRNAs were found in the recurrent group compared with
      the non-recurrent group.ConclusionRecurrence may be attributed to a combination
      of events. Serum biomarkers and drug treatments for IH recurrence must be studied
      further.

PMID- 29019474
TI  - Are Pain-Related Temporomandibular Disorders the Product of an Interaction
      Between Psychological Factors and Self-Reported Bruxism?
AB  - AIMS: To investigate whether pain-related temporomandibular disorders (TMD) are
      the product of an interaction between psychological factors and self-reported
      bruxism activities. METHODS: Patients referred to a specialized clinic for
      complaints of orofacial pain and dysfunction completed a digital questionnaire
      prior to the first clinical visit. The patient sample was then split into a case
      group consisting of 268 patients diagnosed with TMD pain according to the
      Diagnostic Criteria for Temporomandibular Disorders (85.8% women; mean +/-
      standard deviation [SD] age = 40.1 +/- 14.5 years) and a control group consisting
      of 254 patients without any pain in the orofacial area (50.8% women; 46.9 +/-
      13.6 years). The possible moderating roles of six psychological factors
      (depression, somatic symptoms, anxiety, stress, optimism, and prior psychological
      treatment) on the relationship between self-reported bruxism and the clinical
      presence of TMD pain were examined. RESULTS: Patients with TMD pain reported
      significantly more bruxism than patients without any report of orofacial pain.
      Furthermore, bruxism intensity was associated with a variety of psychological
      factors; however, there were no significant interactions between any of the
      psychological factors and bruxism with respect to the clinical presence of TMD
      pain. CONCLUSION: These findings do not support the view that the effect of
      bruxism on TMD pain is stronger in patients who experience higher levels of
      psychological distress compared to those with lower levels of distress.

PMID- 29019472
TI  - Microbiological monitoring of continuous positive airway pressure and
      resuscitation equipment in very-low birth weight infants.
AB  - BackgroundTo investigate the colonization of respiratory equipment and the rate
      of respiratory infections of very-low birth weight (VLBW) infants.MethodsThe
      prospective study includes 26 VLBW infants on continuous airway pressure (CPAP)
      from September until December 2012. Swabs from respiratory equipment and
      colonization/infections were evaluated.ResultsA total of 603 swabs was cultured
      with 298 isolates; 59% of cultures from CPAP equipment (n=337; 95% confidence
      interval (CI; 54;64)) and 19% from ambu bags (n=51; 95% CI (14;24)) were
      positive. Overall, 181/201 CPAP prongs and masks hosted 221 microorganisms.
      Colonization on days 3 and 7 were 93% and 87%, respectively, with an increase in
      pathogens and a decrease in skin flora (79% vs. 68%). Comparing the 58 paired
      swab results from days 3 and 7 showed an increase in Gram-negative bacteria
      (P=0.014). Eighteen infants had positive weekly screening results, with similar
      colonization of CPAP equipment, dominated by Enterobacteriacae. Pneumonia was
      diagnosed in two infants.ConclusionOf the CPAP equipment close to the patient,
      90% was colonized with microorganisms increasing during 1 week of CPAP. The
      pathogens were dominated by gastrointestinal bacteria, and persisted over weeks.
      Frequent cleaning did not prevent pneumonia, although pneumonia rates were rare.

PMID- 29019475
TI  - Orofacial Pain Associated with Vasospastic Angina: A Case Report.
AB  - The primary symptom of ischemic heart disease is typically chest pain, but in
      some cases, this pain may radiate to the maxillofacial region. This article
      describes the case of a 44-year-old man with orofacial pain of cardiac origin.
      The patient was suspected to be suffering from cardiac disease by the oral and
      maxillofacial surgeon and was referred to a cardiologist, where he received a
      heart examination. The patient was diagnosed by means of cardiac catheterization
      as having coronary spastic angina. During catheterization, intracoronary
      ergonovine maleate induced orofacial pain that was almost the same in character
      and intensity as the patient's first episode. The orofacial pain was considered
      to be telalgia from coronary spastic angina. The patient started medication on
      the same day as the diagnosis. There was no recurrence of any symptoms. These
      findings indicate that in such cases, the dentist may contribute to identifying
      ischemic heart disease and should refer the patient to a cardiologist.

PMID- 29019476
TI  - Parenting a Child with Juvenile Idiopathic Arthritis, Orofacial Pain, and
      Dysfunction: A Qualitative Study.
AB  - AIMS: To deepen knowledge of how parents of children diagnosed with juvenile
      idiopathic arthritis (JIA) perceive the orofacial manifestations of the disease,
      its treatments, and their encounters with dental care providers. METHODS: A total
      of 15 interviews with parents of JIA patients (3 to 16 years old) with orofacial
      pain were analyzed according to classic grounded theory. RESULTS: The main
      problem was identified as controlling an unpredictable life situation that
      includes a child with JIA. To solve this main problem, the parent was trying to
      comprehend, help, and speak for the child with disability, a solution that
      permeated their life situation. This was therefore identified as the core
      category, and the other categories (ie, ways parents responded to their
      situation) were reflecting on and re-evaluating the life situation, monitoring
      the child's symptoms and treatments, adapting everyday routines, seeking doctors
      and information, influencing school and society, and managing job and family
      finances. The main problem and the various categories formed a model reflecting
      how parents of children diagnosed with JIA act and think. CONCLUSION: It is
      extremely important for caregivers to understand the complexity of the life
      situation for parents whose children have been diagnosed with JIA. They must
      facilitate the parent's understanding of how this disease can influence the
      orofacial area and day-to-day care.

PMID- 29019477
TI  - Comparing Axis II Scores According to the RDC/TMD and DC/TMD in Israeli Patients.
AB  - AIMS: To use the Symptom Checklist-90-Revised (SCL-90-R)-based instruments of the
      Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and the
      Primary Care Evaluation of Mental Disorders (PRIME-MD)-based instruments of the
      Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) in order to compare
      these Axis II scores in temporomandibular disorder (TMD) patients. METHODS:
      Demographic and socioeconomic data, Axis I diagnoses, and Axis II evaluations
      (depression, nonspecific physical symptoms, anxiety, and Graded Chronic Pain
      Scale [GCPS]) were compared between two groups of patients-142 TMD patients
      diagnosed according to the RDC/TMD (RDC group) and 157 TMD patients diagnosed
      according to the DC/TMD (DC group). Pearson's chi-square test, Fisher's exact
      test, and Mann-Whitney test were used, and P values were adjusted for multiple
      comparisons. RESULTS: The prevalences of severe depression, nonspecific physical
      symptoms, and anxiety were significantly lower in the DC group than in the RDC
      group, with no differences between groups for Axis I diagnoses, characteristic
      pain intensity (CPI), or GCPS. CONCLUSION: Within the limitations of this study,
      the present findings reveal differences in the presence of severe depression,
      nonspecific physical symptoms, and anxiety between the RDC and DC groups. The
      differences may reflect the cut-off scores of the SCL-90-R and the PRIME-MD
      tools.

PMID- 29019478
TI  - Engineering highly swellable dual-responsive protein-based injectable hydrogels:
      the effects of molecular structure and composition in vivo.
AB  - Stimuli-responsive hydrogels, known as smart hydrogels, are three-dimensional
      amphiphilic or hydrophilic polymer networks that are able to change their volume
      or phase, and other properties, including viscosity, structure, and dimension, in
      response to changes in pH, temperature, and magnetic or electric field. Highly
      swellable, dual-responsive bovine serum albumin (BSA)-based injectable hydrogels
      are prepared here by the chemical conjugation of pH- and temperature-responsive
      oligo(sulfamethazine acrylate-co-N-isopropylacrylamide) (oligo(SMA-co-NIPAM))
      copolymers on the surface of BSA through carbodiimide-mediated chemistry. The pH-
      and temperature-responsive oligomer-bearing BSA conjugates show rapid sol-to-gel
      phase transition properties. Specifically, the free-flowing conjugates at high pH
      (pH 8.4, 23  degrees C) are transformed to a viscoelastic gel under physiological
      conditions (pH 7.4, 37  degrees C). The swelling ratio, gel strength, and pore
      size of the BSA hydrogel were tuned by altering the conjugation ratio of the
      oligo(SMA-co-NIPAM) copolymers of various lengths and compositions to BSA.
      Subcutaneously administered BSA conjugate sols into the dorsal region of Sprague
      Dawley rats formed an in situ gel. When the oligo(NIPAM) content in the hydrogel
      was high, the degradation rate of BSA hydrogels was remarkably slow, and two
      weeks after in vivo administration, the hydrogels with high oligo(NIPAM) had
      swollen more than 4-fold. An in vivo biodegradation study demonstrated that no
      necrosis or hemorrhage was observed in the tissues with the hydrogels. The
      concurrent stimuli-responsivity under physiological conditions and high
      elasticity suggest that these smart hydrogels may open a new avenue for hydrogel
      applications.

PMID- 29019479
TI  - Facile insertion of a cyclic alkyl(amino) carbene carbon into the B-B bond of
      diboron(4) reagents.
AB  - We report herein the room temperature insertion of the carbene carbon atom of the
      cyclic (alkyl)(amino) carbene cAACMe into the B-B single bonds of the diboron(4)
      compounds B2pin2, B2cat2, B2neop2, and B2eg2 (pin = pinacolato, cat =
      catecholato, neop = neopentylglycolato, eg = ethyleneglycolato).

PMID- 29019481
TI  - Protein metalation by metal-based drugs: X-ray crystallography and mass
      spectrometry studies.
AB  - The combined use of X-ray crystallography and mass spectrometry represents a
      valuable strategy to investigate and characterize protein metalation induced by
      anticancer metal-based drugs. Here, we summarize a series of significant results
      recently obtained in our laboratories upon the examination of the structures of
      several adducts of proteins with representative metallodrugs (mostly containing
      ruthenium, gold and platinum). The general mechanisms of protein metalation that
      emerge from a careful comparative analysis of these structures are illustrated
      and their mechanistic implications are discussed. Possible directions for future
      work in the field are delineated.

PMID- 29019480
TI  - Design and development of polysaccharide hemostatic materials and their
      hemostatic mechanism.
AB  - The formation of stable blood clots or hemostasis is essential to prevent major
      blood loss and death from excessive bleeding. However, the body's own coagulation
      process is not able to accomplish timely hemostasis without the assistance of
      hemostatic agents. For developing novel topical hemostatic agents, tissue
      adhesives and sealants, it is necessary to understand the coagulation process and
      the hemostasis mechanism of different materials. Among hemostatic materials,
      polysaccharides are naturally derived polymers having excellent biodegradable and
      biocompatible properties. This review provides an overview of polysaccharide
      based hemostatic materials and agents, including their advantages and drawbacks
      in hemostatic applications. Furthermore, polysaccharide-based hemostatic
      materials with anti-microbial and healing functions are also introduced.

PMID- 29019482
TI  - Novel poly(vinyl alcohol)-based amphiphilic nanogels by non-covalent boric acid
      crosslinking of polymeric micelles.
AB  - In this work, we report a new type of poly(vinyl alcohol)-g-poly(N
      isopropylacrylamide) (PVA-g-PNiPAAm) amphiphilic nanogel produced by the non
      covalent crosslinking of PVA polyol domains in preformed polymeric micelles with
      boric acid. The nanomaterials showed sizes in the 100-250 nm range (DLS) and a
      spherical morphology (HR-SEM). We demonstrated that the size of the polymeric
      micelles could be fine-tuned by changing the concentration (and the aggregation
      pattern) of the polymeric amphiphile in water. Upon crosslinking, the polymeric
      micelles turned into physically stable amphiphilic nanogels that displayed both
      size and size distribution similar to the micellar precursor for up to two weeks,
      even under disfavored conditions of concentration and temperature that, in the
      case of non-crosslinked counterparts, resulted in quick disassembly. In addition,
      we show for the first time the feasibility of spray-drying technology to
      consolidate the 3D network formed between PVA and boric acid and to produce
      stable powders that can be reconstituted upon use at any desired concentration.
      Moreover, the formation of a borated surface conferred the nanogels with good
      mucoadhesiveness in vitro. Finally, these novel nanomaterials showed optimal cell
      compatibility in a model of the intestinal epithelium, the Caco2 cell line.
      Overall results demonstrate the unprecedented versatility of the proposed modular
      approach and opens completely new horizons in the application of polymeric
      micelles and other self-assembled polymeric nanomaterials in diagnostics and
      therapeutics.

PMID- 29019483
TI  - Large irradiation doses can improve the fast neutron/gamma discriminating
      capability of plastic scintillators.
AB  - When new materials appear as potential alternatives for radiation detection,
      several criteria have to be fulfilled. The one presented herein is the response
      variation to large irradiation doses of neutron/gamma discriminating plastic
      scintillators. Thus, several samples were exposed to high gamma doses reaching 10
      kGy. They were characterized in terms of gamma spectrometry and fast
      neutron/gamma discrimination, prior to and after irradiation. Results show an
      unexpected increase of the figure of merit (FoM), which is the numerical value
      for n/gamma discrimination performances. An in-depth investigation evaluates the
      physicochemical impact of such large doses within the material. The
      characterization includes photophysics, radiation/matter interaction and chemical
      analyses (EPR, 1H NMR, fluorescence spectroscopy and HRMS).

PMID- 29019484
TI  - Thermoelectric properties of Se and Zn/Cd/Sn double substituted Co4Sb12
      skutterudite compounds.
AB  - Double-doped skutterudite Co4Sb12 compounds are reported as a good n-type
      thermoelectric system which operate in the mid-temperature range. Instead of
      filling the skutterudite phase to minimize the thermal conductivity, it is
      proposed to induce disorder in the pnicogen rings by the substitution of Zn/Cd/Sn
      and Se. Structural analyses of the prepared compounds were carried out by
      Rietveld refinement process. The compounds show overall reduction in thermal
      conductivity, particularly the lattice part. Since vibration modes of heat
      carrying phonons predominantly fall within the frequency range of the pnicogen
      rings, double substitutions on those pnicogen rings are particularly helpful in
      distracting the thermal transport. As larger mass difference and strain
      fluctuations can more efficiently scatter the heat-carrying phonons through short
      mean free path, it drastically restrains the thermal transport of the compounds,
      and this effect has been successfully demonstrated using the Debye-Callaway
      Klemens model. Smooth electrical transport behavior is observed in all the
      samples and the power factor values are quite comparable to reported values.
      Phonon scattering mechanism and local distortion in the structure of the
      compounds is also evaluated by Raman analysis. Collectively, a high peak ZT of
      ~0.7 and ~0.65 at 673 K is obtained for Co4Sb11.86Se0.1Zn0.04 and
      Co4Sb11.86Se0.1Sn0.04 compounds which shows more than 50% enhancement relative to
      the pristine Co4Sb12 system.

PMID- 29019485
TI  - Dynamics theory for molecular liquids based on an interaction site model.
AB  - Dynamics theories for molecular liquids based on an interaction site model have
      been developed over the past few decades and proved to be powerful tools to
      investigate various dynamical phenomena. In many of these theories, equations of
      time correlation functions are formulated by using the Zwanzig-Mori projection
      operator. Since algebriac equations are directly treated in these statistical
      mechanical approaches, the obtained dynamical properties are essentially free
      from statistical error. This perspective presents the theoretical framework of
      such theories and their applications, including visualization of diffusion
      processes, collective excitations, solvation dynamics, transport properties, and
      diffusion controlled reactions.

PMID- 29019488
TI  - Fluorescent chemosensors: the past, present and future.
AB  - Fluorescent chemosensors for ions and neutral analytes have been widely applied
      in many diverse fields such as biology, physiology, pharmacology, and
      environmental sciences. The field of fluorescent chemosensors has been in
      existence for about 150 years. In this time, a large range of fluorescent
      chemosensors have been established for the detection of biologically and/or
      environmentally important species. Despite the progress made in this field,
      several problems and challenges still exist. This tutorial review introduces the
      history and provides a general overview of the development in the research of
      fluorescent sensors, often referred to as chemosensors. This will be achieved by
      highlighting some pioneering and representative works from about 40 groups in the
      world that have made substantial contributions to this field. The basic
      principles involved in the design of chemosensors for specific analytes, problems
      and challenges in the field as well as possible future research directions are
      covered. The application of chemosensors in various established and emerging
      biotechnologies, is very bright.

PMID- 29019493
TI  - Large-scale metal nanoelectrode arrays based on printed nanowire lithography for
      nanowire complementary inverters.
AB  - Nanowire (NW) complementary inverters based on NW channels and NW electrodes are
      a promising core logic unit of future subminiature, high density and textile-type
      configured electronic circuits. However, existing approaches based on short NWs
      (<150 MUm) or non-woven nanofibers cannot provide precisely-coordinated NW
      inverters due to the difficulty in the position and alignment control of each NW.
      In particular, the large-scale fabrication of highly-aligned metal nanoelectrode
      (NE) arrays with low resistivity is a challenging issue. Here, we developed large
      scale-aligned AgNE arrays with very low resistivity by using printed NW
      lithography, and then demonstrated NW complementary inverters by combining with
      direct-printed organic semiconducting NWs. The width of the AgNEs was controlled
      from 250 to 1000 nm; their resistivity was 2.6 MUOmega cm which is quite
      comparable with that of Ag films (1.6 MUOmega cm). We expect that this approach
      will facilitate advances in the large-scale fabrication of nanoelectronics which
      will be compatible with printed electronics.

PMID- 29019494
TI  - Relativistic DFT investigation of electronic structure effects arising from
      doping the Au25 nanocluster with transition metals.
AB  - We perform a theoretical investigation using density functional theory (DFT) and
      time-dependent DFT (TDDFT) on the doping of the Au25(SR)18-1 nanocluster with
      group IX transition metals (M = cobalt, rhodium and iridium). Different doping
      motifs, charge states and spin multiplicities were considered for the single-atom
      doped nanoclusters. Our results show that the interaction (or the lack of
      interaction) between the d-type energy levels that mainly originate from the
      dopant atom and the super-atomic levels plays an important role in the
      energetics, the electronic structure and the optical properties of the doped
      systems. The evaluated MAu24(SR)18q (q = -1, -3) systems favor an endohedral
      disposition of the doping atom typically in a singlet ground state, with either a
      6- or 8-valence electron icosahedral core. For the sake of comparison, the role
      of the d energy levels in the electronic structure of a variety of doped
      Au25(SR)18-1 nanoclusters was investigated for dopant atoms from other families
      such as Cd, Ag and Pd. Finally, the effect of spin-orbit coupling (SOC) on the
      electronic structure and absorption spectra was determined. The information in
      this study regarding the relative energetics of the d-based and super-atom energy
      levels can be useful to extend our understanding of the preferred doping modes of
      different transition metals in protected gold nanoclusters.

PMID- 29019495
TI  - A novel visible light responsive nanosystem for cancer treatment.
AB  - A novel singlet-oxygen sensitive drug delivery nanocarrier able to release its
      cargo after exposure to visible (Vis) light from a common lamp is presented. This
      nanodevice is based on mesoporous silica nanoparticles (MSN) decorated with
      porphyrin-caps grafted via reactive oxygen species (ROS)-cleavable linkages. In
      the presence of Vis light porphyrin-nanocaps produce singlet oxygen molecules
      that break the sensitive-linker, which triggers pore uncapping and therefore
      allows the release of the entrapped cargo (topotecan, TOP). This new system takes
      advantage of the non-toxicity and greater penetration capacity of Vis radiation
      and a double antitumor effect due to the drug release and the ROS production. In
      vitro tests with HOS osteosarcoma cancer cells reveal that TOP is able to be
      released in a controlled fashion inside the tumor cells. This research work
      constitutes a proof of concept that opens up promising expectations in the search
      for new alternatives for the treatment of cancer.

PMID- 29019496
TI  - Mechanochemically prepared SrFCl nanophosphor co-doped with Yb3+ and Er3+ for
      detecting ionizing radiation by upconversion luminescence.
AB  - We report a novel method for detecting ionizing radiation by employing the
      phenomenon of upconversion luminescence. Nanocrystalline SrFCl:Yb3+/Er3+ was
      prepared by ball-milling and characterized by powder X-ray diffraction (XRD),
      transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy
      (XPS). The photoluminescence properties of nanocrystalline SrFCl:Yb3+, SrFCl:Er3+
      and SrFCl:Yb3+/Er3+ before and after X-irradiation were investigated. The results
      demonstrate that both Yb3+ and Er3+ ions in the SrFCl host are reduced to their
      divalent state upon X-ray exposure. Under 980 nm infrared excitation,
      SrFCl:Yb3+/Er3+ nanocrystals displayed efficient upconversion luminescence. The
      upconversion luminescence intensity gradually decreased with increasing X
      irradiation in a double exponential fashion with rate constants of k1 = 0.08 Gy-1
      and k2 = 0.01 Gy-1. In comparison with other X-ray storage phosphors, the present
      system shows a much higher stability of stored information since it is not
      subject to photobleaching in the read-out process. This is the first report on
      detecting ionizing radiation by upconversion luminescence, with the potential for
      improved read-out performance over traditional storage phosphors. Possible
      applications of the present phosphor include bioimaging and in vivo cell-level X
      ray dose monitoring.

PMID- 29019497
TI  - TEM nano-Moire evaluation for an invisible lattice structure near the grain
      interface.
AB  - Moire technique is a powerful, important and effective tool for scientific
      research, from the nano-scale to the macro-scale, which is essentially the
      interference between two or more periodic structures with a similar frequency. In
      this study, an inverse transmission electron microscopy (TEM) nano-Moire method
      has been proposed, for the first time, to reconstruct an invisible lattice
      structure near the grain interface, where only one kind of lattice structure and
      Moire fringe were visible in a high resolution TEM (HRTEM) image simultaneously.
      The inversion process was performed in detail. Three rules were put forward to
      ensure the uniqueness of the inversion result. The HRTEM image of a top
      coat/thermally grown oxide interface in a thermal barrier coating (TBC) structure
      was observed with coexisting visible lattice and Moire fringes. Using the inverse
      TEM nano-Moire method, the invisible lower layer lattice was inversed and a 3
      dimensional structure near the interface was also reconstructed to some degree.
      The real strain field of oriented invisible and visible lattices and the relative
      strain field of the Moire fringe in the grain and near the grain boundary were
      obtained simultaneously through the subset geometric phase analysis method. The
      possible failure mechanism and position of the TBC spallation from the nano-scale
      to the micro-scale were discussed.

PMID- 29019498
TI  - Characterization of carboxylate nanoparticle adhesion with the fungal pathogen
      Candida albicans.
AB  - Candida albicans is the lead fungal pathogen of nosocomial bloodstream infections
      worldwide and has mortality rates of 43%. Nanoparticles have been identified as a
      means to improve medical outcomes for Candida infections, enabling sample
      concentration, serving as contrast agents for in vivo imaging, and delivering
      therapeutics. However, little is known about how nanoparticles interact with the
      fungal cell wall. In this report we used laser scanning confocal microscopy to
      examine the interaction of fluorescent polystyrene nanoparticles of specific
      surface chemistry and diameter with C. albicans and mutant strains deficient in
      various C. albicans surface proteins. Carboxylate-functionalized nanoparticles
      adsorbed mainly to the hyphae of wild-type C. albicans. The dissociative binding
      constant of the nanoparticles was ~150, ~30 and ~2.5 pM for 40, 100 nm and 200 nm
      diameter particles, respectively. A significant reduction in particle binding was
      observed with a Deltaals3 strain compared to wild-type strains, identifying the
      Als3 adhesin as the main mediator of this nanoparticle adhesion. In the absence
      of Als3, nanoparticles bound to germ tubes and yeast cells in a pattern
      resembling the localization of Als1, indicating Als1 also plays a role.
      Nanoparticle surface charge was shown to influence binding - positively charged
      amine-functionalized nanoparticles failed to bind to the hyphal cell wall.
      Binding of carboxylate-functionalized nanoparticles was observed in the presence
      of serum, though interactions were reduced. These observations show that Als3 and
      Als1 are important targets for nanoparticle-mediated diagnostics and
      therapeutics, and provide direction for optimal diameter and surface
      characteristics of nanoparticles that bind to the fungal cell wall.

PMID- 29019492
TI  - Self-assembling prodrugs.
AB  - Covalent modification of therapeutic compounds is a clinically proven strategy to
      devise prodrugs with enhanced treatment efficacies. This prodrug strategy relies
      on the modified drugs that possess advantageous pharmacokinetic properties and
      administration routes over their parent drug. Self-assembling prodrugs represent
      an emerging class of therapeutic agents capable of spontaneously associating into
      well-defined supramolecular nanostructures in aqueous solutions. The self
      assembly of prodrugs expands the functional space of conventional prodrug design,
      affording a possible pathway to more effective therapies as the assembled
      nanostructure possesses distinct physicochemical properties and interaction
      potentials that can be tailored to specific administration routes and disease
      treatment. In this review, we will discuss the various types of self-assembling
      prodrugs in development, providing an overview of the methods used to control
      their structure and function and, ultimately, our perspective on their current
      and future potential.

PMID- 29019499
TI  - Iodine induced 1-D lamellar self assembly in organic ionic crystals for solid
      state dye sensitized solar cells.
AB  - A novel saturated heterocyclic organic ionic crystal, piperidinium iodide (PiHI),
      is synthesized by a facile route and applied as a solid electrolyte in Dye
      Sensitized Solar Cells (ss-DSSCs). Upon addition of a small quantity of iodine,
      PiHI self-assembles into a 1D lamellar micro crystalline structure that shows
      anisotropic conductivity. The two-component PiHI was characterized by using
      electrochemical impedance spectroscopy, cyclic voltammetry, steady state
      voltammetry, FT-IR, and Raman spectroscopy. Wide angle X-ray diffraction (XRD)
      measurement confirms the presence of long range 1D lamellar channels that pave
      the way for the diffusion of the redox couple I-/I3- and exhibit high anisotropic
      conductivity. The ionic conductivity of 1D PiHI (with I2) aligned perpendicular
      to the electrode, sigma? (15.46 mS cm-1), is 1.5 times higher than that aligned
      parallel to the electrode sigma? = 10.32 mS cm-1. The ss-DSSC devices with these
      self-assembled ordered ionic crystals with a carbazole based sensitizer (SK1)
      achieved a power conversion efficiency (PCE) of 4.2% and 5.2% for ?al and ?ar
      arrangement, respectively. The reported PCEs are better than that obtained from a
      classical liquid electrolyte with SK1 sensitizers. The electron kinetics at
      various interfaces of ss-DSSC devices was evaluated using Electrochemical
      Impedance Spectroscopy (EIS) measurements. The presence of a saturated cyclic
      structure promotes close packing through H-bonding and electrostatic
      interactions, which make ss-DSSC devices more stable up to 600 h under
      illumination of 1 sun.

PMID- 29019500
TI  - I2-Catalyzed cross dehydrogenative coupling: rapid access to benzoxazinones and
      quinazolinones.
AB  - An efficient and applicable I2-catalyzed intramolecular dehydrogenative C-O/C-N
      coupling reaction via activating the C-H bond adjacent to the N atom has been
      developed to provide dozens of substituted benzoxazinones (31 examples) and
      quinazolinones (5 examples) in good to excellent yields (up to 98%). This one-pot
      methodology has significant advantages, including a metal-free process, broad
      substrate scope, high atom economy, and simple operation. This strategy goes
      through an iminium intermediate followed by nucleophilic attack to provide the
      desired products.

PMID- 29019501
TI  - Synthesis of anatase TiO2 with exposed (100) facets and enhanced
      electrorheological activity.
AB  - Herein, a simple hydrothermal method is employed to synthesize anatase TiO2 with
      dominant (100) facets, as a precursor, using titanate nanofibers derived from
      alkali treatment. Scanning electron microscopy (SEM), transmission electron
      microscopy (TEM) and X-ray diffraction (XRD) are carried out to confirm the
      surface morphology and phase structure of the TiO2 product. The formation
      mechanism of TiO2 enclosed by (100) and (101) facets is deduced to be the
      selective adsorption of OH- on the (100) facets of anatase TiO2.
      Electroheological (ER) experiments indicate that the tetragonal-facet-rod anatase
      TiO2 with exposed (100) facets exhibits an excellent ER performance with a high
      ER efficiency of up to 52.5, which results from the anisotropy of its special
      morphology. In addition, the effect of shape on its dielectric property is
      investigated via broadband dielectric spectroscopy.

PMID- 29019503
TI  - Carrier scattering in quasi-free standing graphene on hexagonal boron nitride.
AB  - Graphene, a two-dimensional material with a honeycomb lattice, has been promoted
      as a next generation material because of its ultrafast charge carriers and
      superior electrical properties. Hexagonal boron nitride (h-BN) is an insulator
      explored as an ideal substrate for graphene with lattice-matching. Using raido
      frequency (RF) transmission measurement which provides specific characteristics
      of carrier scattering in a device, we profoundly investigated the electrical
      properties of quasi-free standing graphene on h-BN. RF devices with graphene
      supported and encapsulated with h-BN were fabricated to analyze the RF signal at
      low temperatures from 100 to 300 K. We demonstrated the carrier behavior in
      graphene with thermally excited carriers and acoustic photon scattering according
      to heat energy. Both h-BN supported and encapsulated graphene showed a
      significant enhancement in RF transmission, which is close to a gold
      interconnector. Our device with graphene on h-BN exhibited concealed nonlinear
      characteristics at a specific temperature of 180 K due to the internal effects of
      acoustic phonon scattering, while a usual device with graphene on SiO2/Si
      provided a linear variation. To anticipate the potential for electronic
      applications, the electrical circuit properties such as impedance, resistance,
      and inductance were extracted from the results of RF measurement.

PMID- 29019504
TI  - Synthesis of functionalized imidazolidine-2-thiones via NHC/base-promoted aza
      benzoin/aza-acetalization domino reactions.
AB  - A strategy for the synthesis of biologically relevant 5-hydroxy-imidazolidine-2
      thione derivatives is presented. A novel class of alpha-sulfonylamines have been
      suitably prepared (46-81% yield) as precursors of formal benzylidenethiourea
      acceptors; these are generated in situ and intercepted by N-heterocyclic carbene
      (NHC)-activated aldehydes affording open-chain aza-benzoin-type adducts, which in
      turn undergo an intramolecular aza-acetalization reaction in a one-pot fashion. A
      thiazolium salt/triethylamine couple proved to be the more effective system to
      trigger the domino sequence giving the target heterocycles in good yields (45
      97%) and diastereoselectivities (up to 99 : 1 dr). The multigram scale synthesis
      and elaboration of a selected 5-hydroxy-imidazolidine-2-thione compound is also
      described.

PMID- 29019505
TI  - Insights into the growth mechanism of REF3 (RE = La-Lu, Y) nanocrystals:
      hexagonal and/or orthorhombic.
AB  - The synthesis of REF3 (RE = La-Lu, Y) nanocrystals with controlled phase
      structures has so far remained a challenge. Herein we have developed a one-for
      all synthetic procedure that allows the successful synthesis of REF3 nanocrystals
      in a controlled manner. Experimental results showed that the radius of RE ions
      determines the phase structure: pure hexagonal REF3 (RE = La-Eu), a mixture of
      hexagonal and orthorhombic REF3 (RE = Gd), and pure orthorhombic REF3 (RE = Tb
      Lu, Y) nanocrystals are obtained along with the decrease of the ionic radius. As
      Gd is positioned exactly in the middle of the lanthanides row, GdF3 nanocrystals
      were used as a model to further investigate how the molar ratio of F- : Gd3+, the
      doping of RE ions with different ionic radii, and the doping concentration of
      certain RE ions affects the crystal structure of the final product.

PMID- 29019509
TI  - Hydroxylation of anilides by engineered cytochrome P450BM3.
AB  - Biocatalytic direct monohydroxylation of anilides has been achieved on
      preparative scale using mutant cytochrome P450BM3 enzymes. Representative mono-
      and disubstituted N-trifluoromethanesulfonyl anilides are shown to be converted
      in most cases to the corresponding 4-hydroxy derivatives, with substituent
      hydroxylation also occurring in two cases. By mutation variation, it is possible
      to achieve selective hydroxylation of either ring- or side-chain sites.

PMID- 29019510
TI  - Free energy calculations for rings and chains formed by dipolar hard spheres.
AB  - We employ a method based on Monte Carlo grand-canonical simulations to precisely
      calculate partition functions of non-interacting chains and rings formed by
      dipolar hard spheres (DHS) at low temperature. The extended low temperature
      region offered by such cluster calculations, compared to what had been previously
      achieved with standard simulations, opens up the possibility of exploring a part
      of the DHS phase diagram which was inaccessible before. The reported results
      offer the unique opportunity of verifying well-established theoretical models
      based on the ideal gas of cluster approximation in order to clarify their range
      of validity. They also provide the basis for future studies in which cluster
      cluster interactions will be included.

PMID- 29019511
TI  - Acetylenic scaffolding with subphthalocyanines - synthetic scope and elucidation
      of electronic interactions in dimeric structures.
AB  - Boron subphthalocyanines (SubPcs) are powerful chromophoric heterocycles that can
      be synthetically modified at both axial and peripheral positions. Acetylenic
      scaffolding offers the possibility of building large, unsaturated carbon-rich
      frameworks that can exhibit excellent electron-accepting properties, and when
      combined with SubPcs it presents a convenient method for preparing interesting
      chromophore-acceptor architectures. Here we present synthetic methodologies for
      the post-functionalization of the relatively sensitive SubPc chromophore via
      acetylenic coupling reactions. By gentle AlCl3-mediated alkynylation at the axial
      boron position, we managed to anchor two SubPcs to the geminal positions of a
      tetraethynylethene (TEE) acceptor. Convenient conditions that allow for stepwise
      desilylations of trimethylsilyl (TMS) and triisopropylsilyl (TIPS) protected
      SubPc-decorated acetylenes using silver(i) fluoride were developed. The resulting
      terminal alkynes were successfully used as coupling partners in metal-catalyzed
      couplings, providing access to larger acetylenic SubPc scaffolds and multiple
      chromophore systems. Moreover, conditions allowing for the conversion of a
      terminal alkyne into an iodoalkyne in the presence of SubPc were developed, and
      the product was subjected to cross-coupling reactions affording unsymmetrical 1,3
      butadiynes. The degree of interactions between two SubPc units as a function of
      the acetylenic bridge was studied by UV-Vis absorption spectroscopy and cyclic
      voltammetry. A TEE bridging unit was found to strongly influence the reductions
      and oxidations of the two SubPc units, while a more flexible bridge had no
      influence.

PMID- 29019513
TI  - Ultrathin beta-tellurium layers grown on highly oriented pyrolytic graphite by
      molecular-beam epitaxy.
AB  - Monolayer tellurium (Te) or tellurene has been suggested by a recent theory as a
      new two-dimensional (2D) system with great electronic and optoelectronic
      promises. Here we present an experimental study of epitaxial Te deposited on
      highly oriented pyrolytic graphite (HOPG) by molecular-beam epitaxy. Scanning
      tunneling microscopy of ultrathin layers of Te reveals rectangular surface cells
      with the cell size consistent with the theoretically predicted beta-tellurene,
      whereas for thicker films, the cell size is more consistent with that of the
      [101[combining macron]0] surface of the bulk Te crystal. Scanning tunneling
      spectroscopy measurements show that the films are semiconductors with the energy
      band gaps decreasing with increasing film thickness, and the gap narrowing occurs
      predominantly at the valence-band maximum (VBM). The latter is understood by
      strong coupling of states at the VBM but a weak coupling at conduction band
      minimum (CBM) as revealed by density functional theory calculations.

PMID- 29019519
TI  - Unusually aggressive immature neo-intimal hyperplasia causing in-stent
      restenosis.
AB  - This image illustrates a very unusual pattern of early and aggressive immature
      neo-intimal hyperplasia in a 52-year-old man with unstable angina, two months
      after deployment of a drug-eluting stent in the proximal left anterior descending
      artery.

PMID- 29019518
TI  - Prevalence and predictive value of electrocardiographic abnormalities in
      pulmonary hypertension: evidence from the Pan-African Pulmonary Hypertension
      Cohort (PAPUCO) study.
AB  - BACKGROUND: Pulmonary hypertension (PH) is prevalent in Africa and is still often
      diagnosed only at an advanced stage, therefore it is associated with poor quality
      of life and survival rates. In resource-limited settings, we assessed the
      diagnostic utility of standard 12-lead electrocardiograms (ECG) to detect
      abnormalities indicating PH. METHODS: Sixty-five patients diagnosed with PH were
      compared with 285 heart disease-free subjects. The prevalence and diagnostic
      performance of ECG features indicative of PH and right heart strain were
      calculated. RESULTS: Compared to the control group, all abnormalities were more
      frequent in the PH cohort where no patient had a completely normal ECG. The most
      prevalent (cases vs control) ECG abnormalities were: pathological Q wave in at
      least two contiguous peripheral leads (47.7 vs 6.7%), left ventricular
      hypertrophy (38.5 vs 9.8%) and p-pulmonale (36.9 vs 20.7%) (all p < 0.05). The
      sensitivity of ECG criteria for right heart strain ranged between 6.2 and 47.7%,
      while specificity ranged between 79.3 and 100%. Negative predictive value ranged
      between 81.5 and 88.9% and positive predictive value between 25 and 100%.
      Positive predictive value was lowest (25%) for right bundle branch block and QRS
      rightaxis deviation (>= 100 degrees ), and highest (100%) for QRS axis >= +100
      degrees  combined with R/S ratio in V1 >= 1 or R in V1 > 7 mm. CONCLUSION: When
      present, signs of PH on ECG strongly indicated disease, but a normal ECG cannot
      rule out disease. ECG patterns focusing on the R and S amplitude in V1 and right
      axis deviation had good specificity and negative predictive values for PH, and
      warrant further investigation with echocardiography.

PMID- 29019520
TI  - Feelings and perceptions of women recovering from anorexia nervosa regarding
      their eating behavior.
AB  - According to the phenomenological approach, observing a phenomenon through the
      perspective of those who lived it may be necessary to acquire fully comprehension
      of it. Therefore, to fully understand the eating behavior during anorexia nervosa
      and during its recovery, this study investigated individual perceptions and
      feelings of three women recovering from anorexia nervosa. This study is
      characterized as a qualitative research with phenomenological approach. The data
      were collected through interviews and analyzed following steps proposed by
      phenomenology researchers. During the anorexia nervosa experience, food
      restriction and irregular meal patterns were observed. Controlling food intake
      was associated with happiness. Guilt, anguish, sadness, fear and anger were
      associated with eating, and food was considered a villain. An obsessive thinking
      about food and a paradox between liking to eat and not wanting to eat were also
      observed. During recovery, it is important to have a more flexible eating
      behavior without negative feelings regarding food; however, feelings of guilty
      and fear were still detected. Perceptions about contact with nutritionists
      revealed the use of ineffective strategies. Although similarities were found in
      all reports, every woman had their own particular and singular experience.
      Rescuing their memories and experiences through their speech was important to
      fully understand and comprehend these personal experiences, and this complete
      understanding may enable health professionals to act more efficiently in the
      treatment of this complex phenomenon.

PMID- 29019521
TI  - [Postpartum depression: prevalence and associated factors].
AB  - The aim was to identify the prevalence of postpartum depression and associated
      factors in women in a medium-sized city in Southern Brazil during 2013. Trained
      female interviewers applied a standardized questionnaire to all participants in
      the city's two maternity hospitals. The study analyzed demographic,
      socioeconomic, behavioral, social support, and disease characteristics. Screening
      for depression was done within the first 48 hours postpartum, using the Edinburgh
      Scale with a cutoff of >= 10. Multivariate analysis used Poisson regression with
      robust variance. Of the 2,687 women interviewed, 14% (95%CI: 12.9-15.6) were
      identified with depression. Factors such as previous depression, third-trimester
      sadness, and family history of depression were associated with increased risk of
      postpartum depression, as were younger maternal age and multiparity. Social
      support from the health team for the pregnant woman was an important protective
      factor, reducing the prevalence of postpartum depression by 23%. The results
      suggest the need for actions by health services for pregnant women in order to
      provide enhanced care during this delicate phase.

PMID- 29019522
TI  - [Regional inequalities in mortality from diabetes mellitus and access to health
      in Argentina].
AB  - The aim of this study was to estimate the mortality burden according to major
      groups of causes, with a focus on diabetes mellitus, as well as differences
      according to the presence or absence of health coverage for Argentina as a whole
      and its regions. The study used the mortality database for individuals 30 years
      or older in 2009-2011, stratified by sex, age bracket, region, underlying cause
      of death, and health coverage. We calculated the mortality rates and years of
      life lost due to premature mortality (YLLs). The quality of mortality records in
      Argentina was unsatisfactory, due to the high proportion of garbage codes for
      deaths. The main results showed a preponderance of chronic non-communicable
      diseases in the mortality burden in all regions of Argentina. In the Northeast,
      one of the country's poorest regions, the burden of mortality was high for all
      groups of causes. The mortality rates and adjusted YLL rates for diabetes
      mellitus were highest in the Cuyo region. There were marked differences in
      adjusted YLL rates according to health coverage status. The study's results
      highlight the need to develop measures to decrease regional and socioeconomic
      inequalities identified by mortality differences in Argentina.

PMID- 29019524
TI  - [Budget impact of the incorporation of GeneXpert MTB/RIF for diagnosis of
      pulmonary tuberculosis from the perspective of the Brazilian Unified National
      Health System, Brazil, 2013-2017].
AB  - The study aimed to estimate the budget impact of GeneXpert MTB/RIF for diagnosis
      of tuberculosis from the perspective of the Brazilian National Program for
      Tuberculosis Control, drawing on a static model using the epidemiological method,
      from 2013 to 2017. GeneXpert MTB/RIF was compared with two diagnostic sputum
      smear tests. The study used epidemiological, population, and cost data, exchange
      rates, and databases from the Brazilian Unified National Health System.
      Sensitivity analysis of scenarios was performed. Incorporation of GeneXpert
      MTB/RIF would cost BRL 147 million (roughly USD 45 million) in five years and
      would have an impact of 23 to 26% in the first two years and some 11% between
      2015 and 2017. The results can support Brazilian and other Latin American health
      administrators in planning and managing the decision on incorporating the
      technology.

PMID- 29019525
TI  - The practice of reporting adverse events in a teaching hospital.
AB  - OBJECTIVE: Understanding the practice of reporting adverse events by health
      professionals. METHOD: A qualitative case study carried out in a teaching
      hospital with participants of the Patient Safety Center and the nursing team. The
      collection took place from May to December 2015, and was conducted through
      interviews, observation and documentary research to treat the data using Content
      Analysis. RESULTS: 31 professionals participated in the study. Three categories
      were elaborated: The practice of reporting adverse events; Barriers in the
      effective practice of notifications; The importance of reporting adverse events.
      CONCLUSION: Notification was permeated by gaps in knowledge, fear of punishment
      and informal communication, generating underreporting. It is necessary to improve
      the interaction between leaders and professionals, with an emphasis on
      communication and educational practice.

PMID- 29019523
TI  - Mental disorders and employment status in the Sao Paulo Metropolitan Area,
      Brazil: gender differences and use of health services.
AB  - Mental disorders are associated with employment status as significant predictors
      and as consequences of unemployment and early retirement. This study describes
      the estimates and associations of 12-month DSM-IV prevalence rates of mental
      disorders and use of health services with employment status by gender in the Sao
      Paulo Metropolitan Area, Brazil. Data from the Sao Paulo Megacity Mental Health
      Survey was analyzed (n = 5,037). This is a population-based study assessing the
      prevalence and determinants of mental disorders among adults, using the Composite
      International Diagnostic Interview. The associations were estimated by odds
      ratios obtained through binomial and multinomial logistic regression. This study
      demonstrates that having mental disorders, especially mood disorders, is
      associated with being inactive or unemployed among men and inactive among women,
      but only having a substance use disorder is associated with being unemployed
      among women. Among those with mental disorders, seeking health care services is
      less frequent within unemployed.

PMID- 29019526
TI  - The cost of transcatheter aortic valve implantation according to different access
      routes.
AB  - OBJECTIVE: Identifying the average direct cost of TAVI (Transcatheter Aortic
      Valve Implantation) for the different access routes. METHOD: This is a research
      with a quantitative, exploratory and descriptive approach carried out in a
      government teaching hospital in the state of Sao Paulo. RESULTS: The average
      direct cost of TAVI procedures by the access routes resulted in R$82,826.38
      (transfemoral route), R$79,440.91 (transaortic route) and R$78,173.41
      (transapical route). The transcatheter valve cost represented a percentage
      variation between 78.47% and 83.14% of the total cost of the procedure. The
      Kruskal-Wallis test was used and presented a statistically significant difference
      between the three access routes: p=0.008. The Bonferroni test showed a difference
      in the association between transfemoral and transapical routes, while no
      statistically significant difference was observed in association with the
      transaortic route. CONCLUSION: The results are important for formulating adequate
      funding policies for the hospital network and understanding the costs according
      to the route facilitates rationalizing resources in order for them to be
      guaranteed for patients who present surgical contraindication to the valve
      implant.

PMID- 29019527
TI  - Factors related to the perceived stigmatization of people living with HIV.
AB  - OBJECTIVE: Analyzing the factors related to perceived stigmatization of people
      living with HIV. METHOD: A cross-sectional study conducted from September of 2014
      to December 2015 with users from a specialized service in Minas Gerais. Data were
      collected through individual instrument application, organized in Microsoft
      Office Excel(r) 2010 spreadsheets and processed on IBM(r) SPSS 23.0. Descriptive
      statistics and multiple linear regression method were used for data analysis,
      adopting statistical significance set at 5.0% (p<=0.05). The study development
      met research ethics standards. RESULTS: 258 users participated in the study. Most
      were males between 40 and 49 years of age, single, with low educational level and
      income. Being between 40 and 49 years of age and having been hospitalized for
      complications related to HIV were positively associated predictors to increased
      stigmatization; while not having comorbidities and not being aware of exposure to
      HIV were predictors associated to reduced stigmatization. CONCLUSION: Given these
      results, we highlight that stigmatization can have an impact on the lives of
      people living with HIV, strengthening their feelings of guilt and shame, which
      can lead to depression, social isolation and abandoning treatment and clinical
      follow-up.

PMID- 29019528
TI  - Children with type 1 Diabetes Mellitus: access to special immunobiological and
      child care.
AB  - OBJECTIVES: Identifying the use of child care situations, the vaccination
      situation and the reasons for non-vaccination, and characterizing whether
      mothers/guardians demonstrate notions about the right to special vaccines for
      children with type 1 Diabetes Mellitus. METHOD: A descriptive, cross-sectional
      study with analysis of quantitative data based on interviews with
      mothers/guardians, particularly regarding access to childcare and vaccination
      against influenza and pneumococcal 23-valent (PPSV). RESULTS: 47
      mothers/guardians participated in the study. The participants reported using more
      specialized services to follow child health, and only a few used the child care
      of the basic health care regularly. There were incomplete vaccination schedules,
      delayed annual follow-ups, missing vaccination cards at the consultations,
      misinformation about the special character of the vaccination, as well as
      emphasis on the need of presenting a specific form to obtain the vaccination,
      resulting in discontinuation of health actions and missed opportunities for
      vaccination. CONCLUSION: Fragilities in child care and immunization actions
      require an increase of primary health care and of the care network, based on
      knowledge and the right to health in order to expand the evidence-based practice,
      access and comprehensiveness.

PMID- 29019529
TI  - Quality of life in patients with chronic wounds: magnitude of changes and
      predictive factors.
AB  - OBJECTIVE: To assess health-related quality of life, its predictors and magnitude
      of changes in health-related quality of life in patients with chronic wounds
      receiving specialized outpatient treatment. METHOD: Secondary, retrospective,
      descriptive, quantitative study with patients with chronic wounds from two
      specialized outpatient services in Brazil assessed through Ferrans & Powers
      Quality of Life Index-Wound Version, Visual Analog Pain Scale, Global Assessment
      Scale, Pressure Ulcer Scale for Healing, sociodemographic and clinical
      questionnaires at baseline and after 60 days of treatment. Data were analyzed by
      ANOVA, Spearman Coefficient, Mann-Whitney test and multivariate logistic
      regression. RESULTS: Twenty-seven patients participated in the study. The overall
      health-related quality of life scale, health and functioning subscale and
      socioeconomic subscale scores increased after 60 days of treatment compared to
      baseline. Pain reduction was a predictor of changes in overall health-related
      quality of life score as well as religious practice in the family subscale. 92.6%
      patients perceived moderate to extensive changes in health-related quality of
      life. CONCLUSION: there was improvement of health-related quality of life for the
      sample studied in the period; pain and religious practice have emerged as
      predictors of changes in health-related quality of life.

PMID- 29019530
TI  - Efficacy of prone position in acute respiratory distress syndrome: overview of
      systematic reviews.
AB  - OBJECTIVE: To identify and integrate the available scientific evidence related to
      the use of the prone position in patients with acute respiratory distress
      syndrome for the reduction of the outcome variable of mortality compared to the
      dorsal decubitus position. METHOD: Overview of systematic reviews or meta
      analyzes of randomized clinical trials. It included studies that evaluated the
      use of prone positioning in patients with acute respiratory distress syndrome
      published between 2014 and 2016. The AMSTAR tool was used to determine the
      methodological quality of studies. The GRADE system was used to establish the
      overall quality of evidence for the mortality outcome. RESULTS: From the search
      strategy, were retrieved seven relevant manuscripts of high methodological
      quality. CONCLUSION: Scientific evidence supports that combined use of protective
      ventilatory strategy and prone positioning for periods between 16 and 20 hours in
      patients with acute respiratory distress syndrome and PaO2/FiO2 ratio lower than
      150 mm/Hg results in significant reduction of mortality rate.

PMID- 29019531
TI  - Development and evaluation of low-cost walker with trunk support for senior
      citizen.
AB  - OBJECTIVE: Develop and evaluate a low-cost walker with trunk support for senior
      citizens. METHOD: Two-stage descriptive study: development of a walker with trunk
      support and evaluation with fourth age senior citizens. RESULTS: Twenty-three
      fourth age senior citizens were selected. The evaluated criteria were the
      immediate influence of the walker on the static stabilometry with baropodometer
      and the evaluation of gait with accelerometers monitoring time and amplitude of
      the hip movement. There was a significant decrease in the body oscillation of
      senior citizens with the use of the developed walker, and there were changes in
      the joint amplitudes of the hip, but they were not significant. CONCLUSION: Using
      low-cost materials, it was possible to develop and equipment that met resistance
      and effectiveness requirements. The walker interfered in the balance of the
      senior citizens, reducing significantly the static body oscillation.

PMID- 29019532
TI  - Are we ready for the implantation of the ERAS protocol?

PMID- 29019533
TI  - Overview of female breast cancer in northern Tocantins - Brazil.
AB  - OBJECTIVE: to evaluate the temporal variation of the percentages of female breast
      cancer in early and late stages and analyze socio-demographic variables
      associated with these stages. METHODS: study of secondary data performed between
      the years of 2000 and 2015 in the Araguaina Regional Hospital - Araguaina - TO -
      Brasil. RESULTS: breast cancer in advanced stages were diagnosed in 51.1% of the
      cases and at an early stage in 48.9%. There was no difference between the
      percentages of patients with early and late stages over the years. Women of
      race/black, illiterate and origin of the southeast of Para presented a higher
      percentage of late staging at diagnosis. CONCLUSIONS: most women was diagnosed
      with advanced disease; the time evolution of the proportion of cases
      (advanced/early) did not demonstrate variational changes over the years;
      association of the disease has been identified in advanced stage in women of
      race/black, illiterate and from the southeast of Para state.

PMID- 29019534
TI  - Evaluation of the quality of life of patients with primary hyperhidrosis
      submitted to videothoracoscopic sympathectomy.
AB  - OBJECTIVE: to evaluate the quality of life of patients undergoing video-assisted
      thoracoscopy for primary hyperhidrosis. METHODS: we evaluated the patients who
      underwent thoracoscopic sympathectomy to treat primary hyperhidrosis by the team
      of thoracic surgery at the University Hospital Gaffree and Guinle - UNIRIO
      between July 2004 and August 2013. It was applied a questionnaire about quality
      of life related to hyperhidrosis since preoperative period until one year after
      the surgery. RESULTS: one hundred twenty two patients answered the questionnaire,
      with a mean age of 25 years, 57% of whom were women. In relation to severity of
      primary hyperhidrosis, 83% of the patients reported as tolerable or somewhat
      tolerable associated with major limitation of quality of life, which it was poor
      or very poor in 82% of cases. Postoperative compensatory hyperhidrosis occurred
      in 78% of patients, but it was regarded as invisible or barely noticeable for 85%
      of these patients, classifying it as acceptable. In 15% of patients, the
      compensatory sweating was classified as disruptive. CONCLUSION: thoracoscopic
      sympathectomy improves the quality of life of patients with primary
      hyperhidrosis. The transitional compensatory hyperhidrosis occurred in most
      patients, but did not improve significantly the quality of life.

PMID- 29019535
TI  - What is the ideal working length for bridge plating osteosynthesis of a femoral
      shaft fracture? A multinational online survey evaluation.
AB  - OBJECTIVE: to evaluate how orthopedic surgeons in Latin America define the
      working length for distinct patterns of femoral shaft fracture. METHODS: a survey
      was developed presenting different options of working length in four femoral
      fracture patterns. The survey was submitted to the participants using Google
      Forms tool. The association between professional characteristics and medical
      management options according to each type of fracture was analyzed by Chi-square
      test, with 5% significance level. RESULTS: seven hundred and seven professionals
      from all Latin America answered the survey. The majority prefered a smaller
      working length for all situations presented in the study. There was a significant
      association between the main interest area and the medical preference for the
      management in fracture types AO 32-B3 and 32-C2 (p<0.05). Other professional
      characteristics had no significant association at the level of 5%. CONCLUSION:
      most of the study participants preferred constructions with smaller working
      length, representing approximately one-third of the total length of the plate,
      regardless of fracture pattern. There was a significant association between the
      main interest area (orthopedic trauma) and medical management options for
      fracture type AO 32-B3 and 32-C2. This can be attributed in part to the fact that
      these two types of fractures are considered, in the view of the authors,
      intermediate patterns in terms of strain. This study reinforces the importance of
      understanding the concept of working length, showing that its calculation remains
      more based on the surgeons' experience than grounded by strong biomechanical
      concepts governing the fracture healing process.

PMID- 29019537
TI  - Initial experience with negative-pressure wound therapy with instillation in
      complex wounds.
AB  - OBJECTIVE: to report the initial experience with Negative-Pressure Wound Therapy
      with instillation in infected or contaminated complex wounds. METHODS: the
      negative-pressure wound therapy with instillation used was V.A.C. Ulta with
      Veraflo instillation (Kinetic Concepts, Inc). The mode of operation was
      continuous with negative pressure set at 125 mmHg for two hours and instillation
      between the pauses. The instillation time was 20 minutes (contact time of the
      topical agent with the wound) and the instilled substance was 0.9% normal saline.
      After adequate preparation of the wound, it was covered with graft or flap.
      RESULTS: ten patients with complex or contaminated wounds were operated on. The
      mean number of NPWTi changes was 1.4, the mean number of surgeries was 2.4, the
      interval until complete wound coverage was 6.3 days, and the interval up to the
      time of discharge was 11.4 days. CONCLUSION: the comparison of the negative
      pressure wound therapy with instillation with two previous studies (historical
      control) evidenced a shorter hospitalization time, favoring TPNi. This study had
      an initial character, making it necessary to conduct a randomized and controlled
      trial to confirm the efficacy of this therapy and verify its cost-effectiveness.

PMID- 29019536
TI  - Trauma mechanism predicts the frequency and the severity of injuries in blunt
      trauma patients.
AB  - OBJECTIVE: to study the correlation of trauma mechanism with frequency and
      severity of injuries in blunt trauma patients. METHODS: retrospective analysis of
      trauma registry in a 15-month period was carried out. Trauma mechanism was
      classified into six types: occupants of four-wheeled vehicles involved in road
      traffic accidents (AUTO), pedestrians struck by road vehicles (PED),
      motorcyclists involved in road traffic accidents (MOTO), falls from height
      (FALL), physical assault with blunt instruments (ASSA) and falls on same level
      (FSL). Injuries with AIS>2 were considered severe. One-way ANOVA, Students t and
      Chi-square tests were used for statistical analysis, considering p<0.05
      significant. RESULTS: trauma mechanism was classified by group for 3639 cases,
      comprising 337 (9.3%) AUTO, 855 (23.5%) PED, 924 (25.4%) MOTO, 455 (12.5%) FALL,
      424 (11.7%) ASSA and 644 (17.7%) FSL. There was significant difference among
      groups when comparing the Revised Trauma Score (RTS), the Injury Severity Score
      (ISS) and the Abbreviated Injury Scale (AIS) of the head, thorax, abdomen and
      extremities (p<0.001). Severe injuries in the head and in the extremities were
      more frequent in PED patients (p<0.001). Severe injuries to the chest were more
      frequent in AUTO (p<0.001). Abdominal injuries were less frequent in FSL
      (p=0.004). Complex fractures of the pelvis and spine were more frequent in FALL
      (p<0.001). Lethality was greater in PED, followed by FALL and AUTO (p<0.001).
      CONCLUSION: trauma mechanism analysis predicted frequency and severity of
      injuries in blunt trauma patients.

PMID- 29019538
TI  - Video-thoracoscopic approach, without suture, of late thoracic esophageal
      perforations.
AB  - OBJECTIVES: to evaluate the use of video-thoracoscopy, in the treatment of late
      perforations of the thoracic esophagus, without suture or organ resection.
      METHODS: retrospective analysis of patients with late diagnosis (> 12 hours) of
      thoracic esophageal perforation treated by video-thoracoscopy, without suture or
      organ resection, over a 15-year period. RESULTS: sixteen patients were operated
      on, ten men and six women, aged between 48 and 66 years, with time between the
      diagnosis of the perforation and the surgery ranging from 16 to 26 hours. All
      patients underwent video-thoracoscopy, with pulmonary decortication, pleural
      loculations approach, opening of the mediastinal pleura near the perforation site
      and debridement of the devitalized tissues, followed by double drainage of the
      pleural cavity. No esophageal suture or resection was performed, and the patients
      evolved with complete closure of the lesions, without deaths. CONCLUSION: the
      video-thoracoscopic surgical approach was able to control pleural infection,
      pulmonary expansion and enable complete regeneration of the esophagus with late
      diagnosed perforation.

PMID- 29019539
TI  - Evaluation of the treatment of the hepatocarcinoma nodules in the patients in
      waiting list for liver transplant.
AB  - OBJECTIVE: to compare the outcome of liver transplantation for hepatocarcinoma in
      submitted or not to locoregional treatment and downstaging regarding survival and
      risk of recurrence in transplant waiting list patients. METHODS: retrospective
      study of patients with hepatocarcinoma undergoing liver transplantation in the
      metropolitan region of Sao Paulo, between January 2007 and December 2011, from a
      deceased donor. The sample consisted of 414 patients. Of these, 29 patients were
      included in the list by downstaging. The other 385 were submitted or not to
      locoregional treatment. RESULTS: the analysis of 414 medical records showed a
      predominance of male patients (79.5%) with average age of 56 years. Treatment of
      the lesions was performed in 56.4% of patients on the waiting list for
      transplant. The most commonly used method was chemoembolization (79%). The
      locoregional patients undergoing treatment had a significant reduction in nodule
      size greater (p<0.001). There was no statistical difference between groups with
      and without locoregional treatment (p=0.744) and on mortality among patients
      enrolled in the Milan criteria or downstaging (p=0.494). CONCLUSION: there was no
      difference in survival and recurrence rate associated with locoregional
      treatment. Patients included by downstaging process had comparable survival
      results to those previously classified as Milan/Brazil criteria.

PMID- 29019540
TI  - Comparative efficacy of immunohistochemical markers in surgical healing.
AB  - OBJECTIVE: to evaluate the efficacy of three immunohistochemical markers involved
      in the wound healing process. METHODS: experimental study of 40 Wistar rats of
      the markers metalloproteinases and matrix metalloproteinase 9 (MMP-9), beta
      transforming growth factor (TGF-beta) and myofibroblasts and smooth muscle actin
      alpha (alpha-MLA) markers, studied from fragments of surgical scar of abdominal
      incision involving skin, aponeurosis and peritoneum. The animals were divided
      into four subgroups of ten according to the day of death, scheduled in three,
      seven, 14 and 21 days. RESULTS: MMP-9 expression showed a progressive increase of
      its concentration, more evident from 7th to 14th days, varying the tissue
      immunoexpression between 2.65% and 11.50% . TGF- beta showed expression at high
      level on the 3rd day, fell in the 7th, rising again in the 14th, with a small
      decrease in the 21st day, varying the tissue immunoexpression between 0.03% and
      2.92%. The alpha-AML presented levels with little variation and a slight
      increase, varying the tissue immunoexpression between 0.88% and 3.23%.
      CONCLUSION: MMP-9 presented as the best marker, followed by TGF-beta. However,
      alpha-AML was not a good indicator of the evolution of tissue repair.

PMID- 29019541
TI  - Laryngeal chondroradionecrosis following radiotherapy.
AB  - OBJECTIVE: to study larynx chondroradionecrosis related to radiotherapy and
      chemotherapy treatment and provide a treatment flowchart. METHODS: retrospective
      study with clinical data analysis of all larynx cancer patients admitted in a two
      tertiary hospital in a five years period. RESULTS: from 131 patients treated for
      larynx cancer, 28 underwent chemoradiotherapy with curative intent and three of
      them presented chondroradionecrosis. They were treated with hiperbaric oxigen
      therapy and surgical debridment following our flowchart, preserving the larynx in
      all. CONCLUSIONS: the incidence of chondroradionecrosis as a complication of
      chemoradiotherapy in our series was 10,7% and the treatment with hiperbaric
      oxigen therapy, based in our flowchart, was effective to control this
      complication.

PMID- 29019542
TI  - Surgical approach of hypertelorbitism in craniofrontonasal dysplasia.
AB  - OBJECTIVE: to present our experience in the hypertelorbitism surgical treatment
      in craniofrontonasal dysplasia. METHODS: retrospective analysis of
      craniofrontonasal dysplasia patients operated through orbital box osteotomy or
      facial bipartition between 1997 and 2015. Surgical data was obtained from medical
      records, complementary tests, photographs, and clinical interviews. Surgical
      results were classified based on the need for additional surgery and orbital
      relapse was calculated. RESULTS: seven female patients were included, of whom
      three (42.86%) underwent orbital box osteotomy and four (57.14%) underwent facial
      bipartition. There was orbital relapse in average of 3.71+/-3,73mm. Surgical
      result according to the need for further surgery was 2.43+/-0.53. CONCLUSION:
      surgical approach to hypertelorbitism in craniofrontonasal dysplasia should be
      individualized, respecting the age at surgery and preferences of patients,
      parents, and surgeons.

PMID- 29019543
TI  - Predictive factors of axillary metastasis in patients with breast cancer and
      positive sentinel lymph node biopsy.
AB  - OBJECTIVE: to evaluate the risk factors for the presence of non-sentinel axillary
      metastatic disease in patients with breast cancer and positive sentinel node
      biopsy. Methods: retrospective cross-sectional study of women with breast cancer
      operated at the Cancer Institute of Ceara between 2002 and 2012 and submitted to
      sentinel lymph node biopsy. RESULTS: Among 946 breast cancer patients, 331
      underwent sentinel lymph node biopsy, which was positive in 83. These patients
      underwent axillary lymphadenectomy and 39 (46%) had metastases in other axillary
      lymph nodes. The variables that were significant for additional axillary disease
      included Ki67>14 (p=0.043), angiolymphatic invasion (p=0.01) and tumor size
      (p=0.027). No association was observed with estrogen, progesterone, tumor grade
      and Her-2 receptors. DISCUSSION: the presence of angiolymphatic invasion and
      tumor size have also been related to additional axillary metastasis in other
      studies. In addition to these variables, the same predictive effect was observed
      when we evaluated Ki67. The validation of these results may allow the
      customization of breast cancer treatment, which may reduce its morbidity.
      CONCLUSION: angiolymphatic invasion, tumor size (T3/T4) and Ki67>14 were factors
      predictive of axillary metastasis involvement in addition to the sentinel lymph
      node.

PMID- 29019544
TI  - Pathophysiological aspects of the low anterior resection syndrome for treatment
      of rectal cancer.
AB  - The number of patients with bowel dysfunction due to the treatment of rectal
      cancer has increased during the recent decades. Anatomical and functional
      disorders after the removal of the rectum are followed by increased stool
      frequency, urgency, multiple evacuations and flatus or stool incontinence
      characterizing the low anterior resection syndrome - LARS. The purpose of this
      article is to present a review of the literature on current concepts and
      pathophysiological aspects of bowel dysfunction after resection of rectal cancer.
      It is essential to understand these mechanisms for a better management of
      patients and recovery of their quality of life.

PMID- 29019545
TI  - A brief history of salivary gland surgery.
AB  - Salivary gland neoplasms are a relatively uncommon disease, with nearly one case
      per 100.000 adults estimated per year and an overall incidence of 1% of all
      neoplasms. The benign neoplasms are majority and the prognosis depends on the
      histologic type, grade, localization, soft tissue infiltration, regional and
      distant metastasis. The main treatment is surgery with caution to facial nerve in
      the major salivary glands, followed by radiotherapy and chemotherapy in selected
      cases. The objective of this review is to provide the lector an historic approach
      about salivary gland diseases treatment, with special attention to the parotid
      neoplasms and its peculiarities associated to those who studied these glands in
      their history course.

PMID- 29019546
TI  - Modified technique for percutaneous endoscopic gastrojejunostomy placement.
AB  - The placement of percutaneous endoscopic gastrojejunostomy (PEG-J) provides diet
      delivery beyond the angle of Treitz, and it is associated with decrease of
      complications related to gastroparesis, such as aspiration pneumonia. There are
      many different techniques to perform a PEG-J described in the literature, with
      variable degrees of technical success. In this article, we suggest modifications
      to the technique of PEG-J placement in order to reduce time of procedure and
      minimize the risk of technical failure.

PMID- 29019547
TI  - Erratum.
AB  - [This corrects the article doi: 10.1590/0100-69912017002012].

PMID- 29019548
TI  - Noncontact three-dimensional evaluation of surface alterations and wear in NiTi
      endodontic instruments.
AB  - The aim of this study was to undertake a qualitative and quantitative assessment
      of nanoscale alterations and wear on the surfaces of nickel-titanium (NiTi)
      endodontic instruments, before and after use, through a high-resolution,
      noncontact, three-dimensional optical profiler, and to verify the accuracy of the
      evaluation method. Cutting blade surfaces of two different brands of NiTi
      endodontic instruments, Reciproc R25 (n = 5) and WaveOne Primary (n = 5), were
      examined and compared before and after two uses in simulated root canals made in
      clear resin blocks. The analyses were performed on three-dimensional images which
      were obtained from surface areas measuring 211 * 211 um, located 3 mm from their
      tips. The quantitative evaluation of the samples was conducted before and after
      the first and second usage, by the recordings of three amplitude parameters. The
      data were subjected to statistical analysis at a 5% level of significance. The
      results revealed statistically significant increases in the surface wear of both
      instruments groups after the second use. The presence of irregularities was found
      on the surface topography of all the instruments, before and after use.
      Regardless of the evaluation stage, most of the defects were observed in the
      WaveOne instruments. The three-dimensional technique was suitable and effective
      for the accurate investigation of the same surfaces of the instruments in
      different periods of time.

PMID- 29019549
TI  - Suppressor of cytokine signaling 1 expression during LPS-induced inflammation and
      bone loss in rats.
AB  - This study aimed to characterize the dynamics of suppressor of cytokine signaling
      (SOCS1) expression in a rat model of lipopolysaccharide-induced periodontitis.
      Wistar rats in the experimental groups were injected three times/week with LPS
      from Escherichia coli on the palatal aspect of the first molars, and control
      animals were injected with vehicle (phosphate-buffered saline). Animals were
      sacrificed 7, 15, and 30 days after the first injection to analyze inflammation
      (stereometric analysis), bone loss (macroscopic analysis), gene expression (qRT
      PCR), and protein expression/activation (Western blotting). The severity of
      inflammation and bone loss associated with LPS-induced periodontitis increased
      from day 7 to day 15, and it was sustained through day 30. Significant (p < 0.05)
      increases in SOCS1, RANKL, OPG, and IFN-gamma gene expression were observed in
      the experimental group versus the control group at day 15. SOCS1 protein
      expression and STAT1 and NF-kappaB activation were increased throughout the 30
      day experimental period. Gingival tissues affected by experimental periodontitis
      express SOCS1, indicating that this protein may potentially downregulate
      signaling events involved in inflammatory reactions and bone loss and thus may
      play a relevant role in the development and progression of periodontal disease.

PMID- 29019550
TI  - Salivary stress biomarkers and anxiety symptoms in children with and without
      temporomandibular disorders.
AB  - The etiology of temporomandibular disorders (TMD), which are considered as a
      heterogeneous group of psychophysiological disturbances, remains a controversial
      issue in clinical dentistry. This study aimed to evaluate whether the salivary
      alpha-amylase (sAA), cortisol levels, and anxiety symptoms differ between
      children with and without TMD. Initially, 316 young subjects were screened in
      public schools (nonreferred sample); 76 subjects aged 7-14 years were selected
      and comprised the TMD and control groups with 38 subjects each matched by sex,
      age, and the presence/absence of sleep bruxism. Four saliva samples were
      collected: upon waking, 30 min and 1 h after awakening (fasting), and at night
      (at 8 PM) on 2 alternate days to examine the diurnal profiles of cortisol and
      sAA. Anxiety symptoms were screened using the Multidimensional Anxiety Scale for
      Children (MASC-Brazilian version). Shapiro-Wilk test, Student's t-test/Mann
      Whitney U test, and correlation tests were used for data analysis. No significant
      differences were observed in the salivary cortisol area under the curve (AUCG
      mean +/- SD = 90.22 +/- 63.36 * 94.21 +/- 63.13 ug/dL/min) and sAA AUCG (mean +/-
      SD = 2544.52 +/- 2142.00 * 2054.03 +/- 1046.89 U/mL/min) between the TMD and
      control groups, respectively (p > 0.05); however, the clinical groups differed in
      social anxiety domain (t = 3.759; CI = 2.609, 8.496), separation/panic (t =
      2.243; CI = 0.309, 5.217), physical symptoms (U = 433.500), and MASC total score
      (t = -3.527; CI = -23.062, -6.412), with a power of the test >80% and large
      effect size (d = 0.80), with no significant correlation between the MASC total
      score, cortisol, and sAA levels. Although children with TMD scored higher in
      anxiety symptoms, no difference was observed in the salivary stress biomarkers
      between children with and without TMD.

PMID- 29019551
TI  - Caries experience and salivary aspects in individuals with fragile X syndrome.
AB  - Fragile X syndrome (FXS) is the most common cause of hereditary mental
      retardation, but studies on the oral health condition of these patients are rare.
      The aim of this study was to determine the experience of dental caries in
      individuals with FXS, by examining the saliva profile, oral hygiene,
      socioeconomic characteristics and use of controlled drugs in these patients.
      Dental health was estimated using the decayed, missing and filled teeth index
      (DMF-T) and sialometry, and the pH value and buffering capacity of the saliva,
      colony forming units of S. mutans (CFU/mL), visible biofilm index, and
      socioeconomic status were all examined. The sample, comprising 23 individuals,
      had an average age of 17.3 +/- 5.6 years, a DMF-T index of 5.5, a diminished
      salivary flow (78.3%), and a low (73.9%) saliva buffering capacity. Most (52.2%)
      individuals presented with a high abundance (CFU/mL) of S. mutans. The experience
      of caries was correlated with salivary parameters, poor oral hygiene, lower
      socioeconomic status and an increased count of S. mutans in saliva.

PMID- 29019552
TI  - Water sorption and solubility of bulk-fill composites polymerized with a third
      generation LED LCU.
AB  - The aim of this study was to compare the degree of water sorption and solubility
      in bulk-fills after curing with a polywave light source. A total of 120 disc
      shaped specimens (8 mm diameter; 4 mm depth) were prepared from three regular
      bulk-fill materials (X-tra Fil, Tetric N-Ceram Bulk Fill, SonicFill), and a
      control material (Filtek Z250), cured in 3 different modes (standard: 1000 mW/cm2
      20 s; high power: 1400 mW/cm2-12 s; xtra power: 3200 mW/cm2-6 s) using a third
      generation light-emitting diode light curing unit. Water sorption and solubility
      levels of the specimens were measured according to the ISO 4049:2009
      specification after storing in distilled water for 30 days. Data were analyzed
      using two-way ANOVA and Tukey's post-hoc test (p < 0.05). The Z250 sample exposed
      to high power presented a higher sorption compared to the X-tra Fil and SonicFill
      samples. In xtra power mode, the values of Z250 and SonicFill were similar to
      each other and higher compared to those of X-tra Fil. Only SonicFill exhibited
      significantly different sorption values depending on the curing mode, the highest
      of which was achieved when using the xtra power mode. The highest solubility
      values were obtained for SonicFill. No statistically significant differences were
      found among other groups. No significant correlation was detected between water
      sorption and solubility. The traditional composite group exhibited a higher water
      sorption values than the bulk-fills. The reduction in polymerization time
      significantly increased the sorption of SonicFill. SonicFill showed the highest
      water solubility value among the composites tested.

PMID- 29019553
TI  - BiodentineTM is cytocompatible with human primary osteoblasts.
AB  - Calcium silicate-based materials have been widely studied due to their
      resemblance to, and similar applicability of, mineral trioxide aggregate (MTA).
      Among these, BiodentineTM (BD) was specifically designed as a "dentin
      replacement" material for applications such as root perforations, apexification,
      treatment of resorptive lesions, and as a retrograde filling material. The
      present study aimed to assess the in vitro response of human primary osteoblasts
      to BD using MTA AngelusTM as a reference material, by simultaneously analyzing
      three different cell viability parameters, namely mitochondrial activity,
      membrane integrity, and cell density. BD and MTA extracts were prepared by
      incubation on culture media for 24 h or 42 days after mixing. Primary human
      osteoblasts were exposed to extracts for 24 h, at 37oC with 5% CO2, and cell
      viability was evaluated by the XTT, NRU, and CVDE assays. Both materials induced
      cell viability levels higher than 70% when extracted for 24 h. However, when
      cells were exposed to extracts with increased conditioning times, MTA presented
      significant cytotoxic effects (p < 0.05) in comparison to the control and MTA at
      24 h. After 42 days, the XTT assay identified a significant reduction in cell
      viability by BD when compared to the control (p<0.05), despite the fact that
      levels above the 70% viability cutoff were attained for biocompatible materials.
      It can be concluded that BD is cytocompatible with human primary osteoblasts,
      indicating its adequacy in direct contact with bone tissues.

PMID- 29019554
TI  - TENSIOMETRIC ANALYSIS OF MESHES USED IN ABDOMINAL VENTRAL WALL DEFECTS IN RATS.
AB  - BACKGROUND: Among the various strategies to avoid exaggerated foreign body
      reaction in the treatment of hernias is the limitation of the amount of
      polypropylene or the use of absorbable material. AIM: To evaluate the healing of
      defects in the abdominal wall of rats, comparing microporous polypropylene,
      macroporous polypropylene and polypropylene/polyglecaprone at the 30o, 60o and
      120o postoperative day. METHODS: Wistar rats were submitted to defect production
      in the ventral abdominal wall, with integrity of the parietal peritoneum.
      Prolene(r), Ultrapro(r) and Bard Soft(r) meshes were used in the correction of
      the defect. Nine subgroups of 10 animals were submitted to euthanasia at 30th,
      60th and 120th postoperative day. Fragments of the abdominal wall of the animals
      were submitted to tensiometric analysis. RESULTS: The tensiometry at the 30th
      postoperative day showed greater resistance of the tissues with Bard Soft(r)
      (macroporous mesh) in relation to the tissues with Prolene(r) (microporous mesh).
      On the 60th postoperative day Bard Soft(r) maintained the superior resistance to
      the tissues comparing to Prolene Mesh(r). On the 120th postoperative day the
      tissues repaired with Ultrapro(r) (macroporous mesh) proved to be more resistant
      than the ones by Prolene(r) (microporous mesh) and Bard Soft(r) (macroporous
      mesh). CONCLUSION: The tissues repaired with macroporous meshes showed greater
      resistance than with microporous meshes at all stages, and at 120 days
      postoperative Ultrapro(r) performed better than the others.

PMID- 29019555
TI  - IMPACT OF OBESITY AND SURGICAL SKILLS IN LAPAROSCOPIC TOTALLY EXTRAPERITONEAL
      HERNIOPLASTY.
AB  - BACKGROUND: Laparoscopic totally extraperitoneal (TEP) hernia repair is a
      technically demanding procedure. Recent studies have identified BMI as an
      independent factor for technical difficulty in the learning period. AIM: To
      analyze the effect of overweight and obesity on the technical difficulties of
      TEP. METHOD: Prospective study on patients who underwent a symptomatic inguinal
      hernia by means of the TEP technique. Were analyzed gender, BMI, previous
      surgery, hernia type, operative time and complications. Technical difficulty was
      defined by operative time, major complications and recurrence. Patients were
      classified into four groups: 1) underweight, if less than 18,5 kg/m2; 2) normal
      range if BMI between 18,5 and 24,9 kg/m2; 3) overweight if BMI between 25-29,9
      kg/m2; and 4) obese if BMI>=30 kg/m2. RESULTS: The cohort had a total of 190
      patients, 185 men and 5 women. BMI values ranged from 16-36 kg/m2 (average 26
      kg/m2). Average operating time was 55.4 min in bilateral hernia (15-150) and 37.8
      min in unilateral (13-150). Time of surgery was statistically correlated with
      increased BMI in the first 93 patients (p=0.049). CONCLUSION: High BMI and
      prolonged operative time are undoubtedly correlated. However, this relationship
      may be statistically significant only in the learning period. Although several
      clinical features can influence surgical time, upon reaching an experienced
      level, surgeons appear to easily handle the challenges.

PMID- 29019556
TI  - COMPARATIVE STUDY OF POSTOPERATIVE PAIN BETWEEN THE LICHTENSTEIN AND LAPAROSCOPY
      SURGICAL TECHNIQUES FOR THE TREATMENT OF UNILATERAL PRIMARY INGUINAL HERNIA.
AB  - BACKGROUND: There are several surgical treatment options for inguinal hernia;
      however, there is no consensus on the literature identifying which surgical
      technique promotes less postoperative pain. AIM: To compare the intensity of
      postoperative pain between the surgical techniques Lichtenstein and
      transabdominal pre-peritoneal laparoscopy for the treatment of unilateral primary
      inguinal hernia. METHODS: Were included 60 patients, of which 30 were operated
      through the Lichtenstein technique and 30 patients through the transabdominal pre
      peritoneal laparoscopy. The pain levels were evaluated through the analogue
      visual scale for 2, 10 and 30 days after the surgery. Additionally, the
      recurrence rate and the presence of chronic pain and paresthesia were evaluated
      12 months after the surgery. RESULTS: Overall, the data analysis showed
      significant differences on pain levels between the surgical techniques. There
      were no significant differences between the pain levels for day 2. However, for
      10 and 30 days after the surgery, the pain levels were significantly lower for
      the patients operated through the transabdominal pre-peritoneal laparoscopy
      technique compared to the Lichtenstein technique. Furthermore, despite no
      recurrent hernias for both surgical techniques, 32 % of patients operated through
      the Lichtenstein technique reported chronic pain and paresthesia 12 months after
      the surgery, compared with 3,6% of patients operated through the transabdominal
      pre-peritoneal laparoscopy technique. CONCLUSION: There are differences between
      the surgical techniques, with the transabdominal pre-peritoneal laparoscopy
      procedure promoting significantly lower postoperative pain (10 and 30 days) and
      chronic pain (12 months) compared to the Lichtenstein procedure.

PMID- 29019558
TI  - LATE EVALUATION OF DYSPHAGIA AFTER HELLER ESOPHAGEAL MYOTOMY WITH DOR
      FUNDOPLICATION FOR ACHALASIA.
AB  - BACKGROUND: All available treatments for achalasia are palliative and aimed to
      eliminate the flow resistance caused by a hypertensive lower esophageal
      sphincter. AIM: To analyze the positive and negative prognostic factors in the
      improvement of dysphagia and to evaluate quality of life in patients undergoing
      surgery to treat esophageal achalasia by comparing findings before, immediately
      after, and in long follow-up. METHODS: A total of 84 patients who underwent
      surgery for achalasia between 2001 and 2014 were retrospectively studied. The
      evaluation protocol with dysphagia scores compared preoperative, immediate (up to
      three months) postoperative and late (over one year) postoperative scores to
      estimate quality of life. RESULTS: The surgical procedure was Heller-Dor in 100%
      of cases, with 84 cases performed laparoscopically. The percent reduction in pre-
      and immediate postoperative lower esophageal sphincter pressurewas 60.35% in the
      success group and 32.49% in the failure group. Regarding the late postoperative
      period, the mean percent decrease was 60.15% in the success group and 31.4% in
      the failure group. The mean overall drop in dysphagia score between the pre- and
      immediate postoperative periods was 7.33 points, which represents a decrease of
      81.17%. CONCLUSIONS: Reduction greater than 60% percent in lower esophageal
      sphincter pressurebetween the pre- and postoperative periods suggests that this
      metric is a predictor of good prognosis for surgical response. Surgical treatment
      was able to have a good affect in quality of life and drastically changed
      dysphagia over time.

PMID- 29019559
TI  - COMPARISON BETWEEN INGUINAL HERNIOTOMIES WITH AND WITHOUT INCISING EXTERNAL
      OBLIQUE APONEUROSIS: A RANDOMIZED CLINICAL TRIAL.
AB  - BACKGROUND: Inguinal herniotomy is the most common surgery performed by pediatric
      surgeons. AIM: To compare the results and complications between two conventional
      methods of pediatric inguinal herniotomy with and without incising external
      oblique aponeurosis in terms of recurrence of hernia and other complications.
      METHODS: This one blinded clinical trial study was conducted on 800 patients with
      indirect inguinal hernia. Inclusion criterion was children with inguinal hernia.
      The first group underwent herniotomy without incising external oblique
      aponeurosis and second group herniotomy with incising external oblique
      aponeurosis. Recurrence of hernia and other complications including ileoinguinal
      nerve damage, hematoma, testicular atrophy, hydrocele, ischemic orchitis, and
      testicular ascent were evaluated. RESULTS: Recurrence and other complications
      with or without incising external oblique aponeurosis had no significant
      difference, exception made to hydrocele significantly differed between the two
      groups, higher in the incision group. CONCLUSION: Herniotomy without incising
      oblique aponeurosis can be appropriate choice and better than herniotomy with
      incising oblique aponeurosis. Children with inguinal herniotomy can be benefit
      without incising oblique aponeurosis, instead of more interventional traditional
      method.

PMID- 29019557
TI  - COLONOSCOPY: RANDOMIZED COMPARATIVE STUDY OF INSUFFLATION WITH CARBON DIOXIDE
      VERSUS AIR.
AB  - BACKGROUND: In Brazil, an increasing number of people are submitted to
      colonoscopy, either for screening or for therapeutic purposes. AIM: To evaluate
      whether there are advantages of using carbon dioxide (CO2) over air for
      insufflation. METHODS: Two hundred and ten of 219 patients were considered
      eligible for this study and were randomized into two groups according to the gas
      insufflation used: Air Group (n=104) and CO2 Group (n=97). The study employed a
      double-blind design. RESULTS: The Air and CO2 Groups were similar in respect to
      bowel preparation evaluated using the Boston scale, age, gender, previous
      surgery, maneuvers necessary for the advancement of the device, and presence of
      polyps, tumors or signs of diverticulitis. However, "waking up with pain" and
      "pain at discharge" were more prevalent in the Air Group, albeit not
      statistically significant, with post-exam bloating seen only in the Air Group.
      The responses to a questionnaire, applied to analyze the late post-exam period,
      showed more comfort with the use of CO2. CONCLUSIONS: The use of CO2 is better
      than air as it avoids post-examination bloating, thereby providing greater
      comfort to patients.

PMID- 29019560
TI  - PANCREATODUODENECTOMY: BRAZILIAN PRACTICE PATTERNS.
AB  - BACKGROUND: Pancreatoduodenectomy is a technically challenging surgical procedure
      with an incidence of postoperative complications ranging from 30% to 61%. The
      procedure requires a high level of experience, and to minimize surgery-related
      complications and mortality, a high-quality standard surgery is imperative. AIM:
      To understand the Brazilian practice patterns for pancreatoduodenectomy. METHOD:
      A questionnaire was designed to obtain an overview of the surgical practice in
      pancreatic cancer, specific training, and experience in pancreatoduodenectomy.
      The survey was sent to members who declared an interest in pancreatic surgery.
      RESULTS: A total of 60 questionnaires were sent, and 52 have returned (86.7%).
      The Southeast had the most survey respondents, with 25 surgeons (48.0%). Only two
      surgeons (3.9%) performed more than 50% of their pancreatoduodenectomies by
      laparoscopy. A classic Whipple procedure was performed by 24 surgeons (46.2%) and
      a standard International Study Group on Pancreatic Surgery lymphadenectomy by 43
      surgeons (82.7%). For reconstruction, pancreaticojejunostomy was performed by 49
      surgeons (94.2%), single limb technique by 41(78.9%), duct-to-mucosa anastomosis
      by 38 (73.1%), internal trans-anastomotic stenting by 26 (50.0%), antecolic route
      of gastric reconstruction by 39 (75.0%), and Braun enteroenterostomy was
      performed by only six surgeons (11.5%). Prophylactic abdominal drainage was
      performed by all surgeons, and somatostatin analogues were utilized by six
      surgeons (11.5%). Early postoperative enteral nutrition was routine for 22
      surgeons (42.3%), and 34 surgeons (65.4%) reported routine use of a nasogastric
      suction tube. CONCLUSION: Heterogeneity was observed in the pancreatoduodenectomy
      practice patterns of surgeons in Brazil, some of them in contrast with
      established evidence in the literature.

PMID- 29019561
TI  - ATORVASTATIN CAN PREVENT HEPATIC REMOTE REPERFUSION INJURY.
AB  - BACKGROUND: Some studies have shown that statins have a promising effect on
      protection against reperfusion injury. AIM: To evaluate the ability of ischemic
      postconditioning, statins and both associated to prevent or minimize reperfusion
      injury in the liver of rats subjected to ischemia and reperfusion by abdominal
      aorta clamping. METHOD: Were used 41 Wistar rats, which were distributed into
      five groups: ischemia and reperfusion (I/R), ischemic postcondictioning (IPC),
      postconditioning + statin (IPC+S), statin (S) and Sham. It was performed a medium
      laparotomy, dissection and isolation of the infra-renal abdominal aorta;
      excepting Sham group, all the others were submitted to the aorta clamping for 70
      min (ischemia) and posterior clamping removing (reperfusion, 70 min). In the IPC
      and IPC+S groups, postconditioning was performed between the ischemia and
      reperfusion phases by four cycles of reperfusion and ischemia lasting 30 s each.
      In IPC+S and S groups, preceding the surgical procedure, administration of 3.4
      mg/day of atorvastatin was performed for seven days by gavage. The left hepatic
      lobe was removed for histological study and euthanasia was performed. RESULTS:
      The mean hepatic injury was 3 in the I/R group, 1.5 in the IPC group, 1.2 in the
      IPC+S group, 1.2 in the S group, and 0 in the SHAM group. The I/R group had a
      higher degree of tissue injury compared to the others in the statistical analysis
      and there was no difference between the others (p<0.01). CONCLUSION: Ischemic
      postconditioning and atorvastatin were able to minimize hepatic reperfusion
      injury, either alone or in combination.

PMID- 29019563
TI  - CRITICAL EVALUATION OF LONG-TERM RESULTS OF MALIGNANT HEPATIC TUMORS TREATED BY
      MEANS CURATIVE LAPAROSCOPIC HEPATECTOMY.
AB  - BACKGROUND: Laparoscopic hepatectomy has presented great importance for treating
      malignant hepatic lesions. AIM: To evaluate its impact in relation to overall
      survival or disease free of the patients operated due different hepatic malignant
      tumors. METHODS: Thirty-four laparoscopic hepatectomies were performed in 31
      patients with malignant neoplasm. Patients were distributed as: Group 1 -
      colorectal metastases (n=14); Group 2 - hepatocellular carcinoma (n=8); and Group
      3 - non-colorectal metastases and intrahepatic cholangiocarcinoma (n=9). The
      conversion rate, morbidity, mortality and tumor recurrence were also evaluated.
      RESULTS: Conversion to open surgery was 6%; morbidity 22%; postoperative
      mortality 3%. There was tumor recurrence in 11 cases. Medians of overall survival
      and disease free survival were respectively 60 and 46 m; however, there was no
      difference among studied groups (p>0,05). CONCLUSION: Long-term outcomes of
      laparoscopic hepatectomy for treating hepatic malignant tumors are satisfactory.
      There is no statistical difference in relation of both overall and disease free
      survival among different groups of hepatic neoplasms.

PMID- 29019564
TI  - THE IMPACT OF THE USE OF SYMBIOTICS IN THE PROGRESSION OF NONALCOHOLIC FATTY
      LIVER DISEASE IN A RAT MODEL.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterized by
      accumulation of intrahepatic lipid. The use of live microorganisms promotes
      beneficial effects; however, the use of symbiotic and its role in NAFLD is not
      yet fully understood. AIM: Verify if the symbiotic administration influences the
      occurrence and progression of NAFLD in rats, after induction of hepatic steatosis
      by high calorie diet. METHOD: Forty-five rats were divided into four groups: G1
      (control); G2 (control+symbiotic); G3 (high calorie+symbiotic) and G4 (high
      calorie), and euthanized after 60 days of diet. Liver disease was evaluated by
      biochemical analysis, IL6 measurement and histological assessment. RESULTS:
      Symbiotic had influence neither on weight gain, nor on coefficient dietary intake
      in G3 and G4. G2 had the greatest weight gain, while G1 had the highest
      coefficient dietary intake between groups. G1 showed higher expression of
      aspartate aminotransferase than those from G2 (150+/-35 mg/dl, and 75+/-5 mg/dl)
      while G4 showed higher expression of the enzyme compared to G3 (141+/-9.7 mg/dl
      to 78+/-4 mg/dl). Liver histology showed different stages of NAFLD between
      groups. G4 animals showed increased serum interleukin-6 when compared to G3
      (240.58+/-53.68 mg/dl and 104.0+/-15.31 mg/dl). CONCLUSION: Symbiotic can reduce
      hepatic aminotransferases and interleukin-6 expression. However, the histology
      showed that the symbiotic was not able to prevent the severity of NAFLD in rats.

PMID- 29019562
TI  - TWELVE YEARS OF EXPERIENCE USING CHOLECYSTOJEJUNAL BY-PASS FOR PALLIATIVE
      TREATMENT OF ADVANCED PANCREATIC CANCER.
AB  - BACKGROUND: The cholecistojejunal bypass is an important resource to treat
      obstructive jaundice due to advanced pancreatic cancer. AIM: To assess the early
      morbidity and mortality of patients with pancreatic cancer who underwent
      cholecystojejunal derivation, and to assess the success of this procedure in
      relieving jaundice. METHOD: This retrospective study examined the medical records
      of patients who underwent surgery. They were categorized into early death and non
      early death groups according to case outcome. RESULTS: 51.8% of the patients were
      male and 48.2% were female. The mean age was 62.3 years. Early mortality was
      14.5%, and 10.9% of them experienced surgical complications. The
      cholecystojejunostomy procedure was effective in 97% of cases. There was a
      tendency of increased survival in women and patients with preoperative serum
      total bilirubin levels below 15 mg/dl. CONCLUSION: Cholecystojejunal derivation
      is a good therapeutic option for relieving jaundice in patients with advanced
      pancreatic cancer, with acceptable rates of morbidity and mortality.

PMID- 29019565
TI  - SLEEVE GASTRECTOMY AND FUNDOPLICATION AS A SINGLE PROCEDURE IN PATIENTS WITH
      OBESITY AND GASTROESOPHAGEAL REFLUX.
AB  - BACKGROUND: Bariatric surgery in Chile has seen an exponential increase in recent
      years, especially in sleeve gastrectomy. Its use is currently discussed in
      patients suffering from gastroesophageal reflux disease. Different options have
      been considered for the management of these patients but up to now laparoscopic
      Roux-en-Y gastric bypass seems to be the best option. Sleeve gastrectomy plus
      concomitant fundoplication or hiatal hernia repair also has been suggested in
      patients having reflux or small hiatal hernia. AIM: To present a cohort of obese
      patients with gatroesophageal reflux undergoing this procedure, which seeks to
      provide the benefits of both laparoscopic gastric sleeve (LSG) and antireflux
      surgery focused on the evaluation of presence of reflux and BMI after surgery,
      and to compare the result observed in this cohort with a previous group of obese
      patients without reflux submitted to sleeve gastrectomy alone. METHODS:
      Retrospective case series in 15 patients who underwent this surgery between the
      years 2003 and 2012. Clinical records were analyzed and values of 24 hr pH
      monitoring, esophageal manometry and clinical outcome were recorded. Results were
      compared to a previous series of patients who underwent LSG. No statistical
      analyses were made. RESULTS: Group A consisted of 15 patients submitted to LSG
      plus fundoplication. 93% (n=14) were female. Mean age was 46.2 years. Mean
      preoperative body mass index (BMI) was 33.9. All patients had altered pH
      monitoring and manometry preoperatively. There was one minor complication
      corresponding to a seroma. There was no perioperative mortality. Group B
      consisted of 23 obese patients who underwent LSG. These patients developed de
      novo reflux, hypotensive LES and esophagitis after the surgery. Group A patients
      showed improvement in esophageal pH monitoring and manometry at three months.
      During long-term follow-up, six underwent revision surgery, four for weight
      regain, one regained weight associated with symptomatic reflux, and one underwent
      re-intervention for reflux. CONCLUSIONS: Good results are observed in the short
      term follow up in both reflux resolution and weight loss. Nevertheless, results
      at long term are discouraging, with 53.3% of the patients requiring revision
      surgery during follow-up.

PMID- 29019566
TI  - PREOPERATIVE MANOMETRY FOR THE SELECTION OF OBESE PEOPLE CANDIDATE TO SLEEVE
      GASTRECTOMY.
AB  - BACKGROUND: Sleeve gastrectomy may alter esophageal motility and lower esophageal
      sphincter pressure. AIM: To detect manometric changings in the esophagus and
      lower esophageal sphincter before and after sleeve gastrectomy in order to select
      patients who could develop postoperative esophageal motilitity disorders and
      lower esophageal sphincter pressure modifications. METHODS: Seventy-three
      patients were selected. All were submitted to manometry before the operation and
      one year after. The variables analyzed were: resting pressure of the lower
      esophageal sphincter, contraction wave amplitude, duration of contraction waves,
      and esophageal peristalsis. Data were compared before and after surgery and to
      the healthy and non-obese control group. Exclusion criteria were: previous
      gastric surgery, reflux symptoms or endoscopic findings of reflux or hiatal
      hernia, diabetes and use of medications that could affect esophageal or lower
      esophageal sphincter motility. RESULTS: 49% of the patients presented
      preoperative manometric alterations: lower esophageal sphincter hypertonia in
      47%, lower esophageal sphincter hypotonia in 22% and increase in contraction wave
      amplitude in 31%. One year after surgery, manometry was altered in 85% of
      patients: lower esophageal sphincter hypertonia in 11%, lower esophageal
      sphincter hypotonia in 52%, increase in contraction wave amplitude in 27% and 10%
      with alteration in esophageal peristalsis. Comparing the results between the
      preoperative and postoperative periods, was found statistical significance for
      the variables of the lower esophageal sphincter, amplitude of contraction waves
      and peristalsis. CONCLUSION: Manometry in the preoperative period of sleeve
      gastrectomy is not an exam to select candidates to this technique.

PMID- 29019568
TI  - GASTRIC SLEEVE SURGERY AS A NEW CLINICAL INDICATION FOR SURGICAL GASTROSTOMY
      AFTER FAILURE OF ENDOSCOPIC APPROACH IN PATIENTS WHO NEED LONG-TERM ENTERAL
      NUTRITION.

PMID- 29019567
TI  - MANAGEMENT OF PANCREATICOPLEURAL FISTULAS SECONDARY TO CHRONIC PANCREATITIS.
AB  - INTRODUCTION: Pancreaticopleural fistula is a rare complication of chronic
      pancreatitis. OBJECTIVE: To describe pancreaticopleural fistula due to chronic
      pancreatitis and perform an extensive review of literature on this topic.
      METHODS: Comprehensive narrative review through online research on the databases
      Medline and Lilacs for articles published over the last 20 years. There were 22
      case reports and four case series selected. RESULTS: The main indication for
      surgical treatment is the failure of clinical and/or endoscopic treatments.
      Surgery is based on internal pancreatic drainage, especially by means of
      pancreaticojejunostomy, and/or pancreatic resections. CONCLUSION:
      Pancreaticopleural fistula is a rare complication of chronic pancreatitis and the
      Frey procedure may be an appropriate therapeutic option in selected cases when
      clinical and endoscopic treatments are unsuccessful.

PMID- 29019569
TI  - Challenges in high technology surgery.

PMID- 29019570
TI  - Thoraco-laparoscopic esophagectomy: thoracic stage in prone position.
AB  - OBJECTIVE: to analyze the National Cancer Institute Abdominopelvic Division (INCA
      / MS/HC I) initial experience with thoraco-laparoscopic esophagectomy with
      thoracic stage in prone position. METHODS: we studied 19 consecutive thoraco
      laparoscopic esophagectomies from may 2012 to august 2014, including ten patients
      with squamous cells carcinoma (five of the middle third and five of the lower
      third) and nine cases of gastroesophageal junction adenocarcinoma (six Siewert I
      and three Siewert II). All procedures were initiated by the prone thoracic stage.
      RESULTS: There were minimal blood loss, optimal mediastinal visualization,
      oncological radicality and no conversions. Surgical morbidity was 42 %, most
      being minor complications (58% Clavien I or II), with few related to the
      technique. The most common complication was cervical anastomotic leak (37%), with
      a low anastomotic stricture rate (two stenosis: 10.53%). We had one (5.3%)
      surgical related death, due to a gastric tube's mediastinal leak, treated by open
      reoperation and neck diversion. The median Intensive Care Unit stay and hospital
      stay were two and 12 days, respectively. The mean thoracoscopic stage duration
      was 77 min. Thirteen patients received neoadjuvant treatment (five squamous cells
      carcinoma and eight gastroesophageal adenocarcinomas). The average lymph node
      sample had 16.4 lymph nodes per patient and 22.67 when separately analyzing
      patients without neoadjuvant treatment. CONCLUSION: the thoraco-laparoscopic
      approach was a safe technique in the surgical treatment of esophageal cancer,
      with a good lymph node sampling.

PMID- 29019571
TI  - Prognostic factors and overall survival of breast cancer in the city of Goiania,
      Brazil: a population-based study.
AB  - OBJECTIVE: to analyze the overall survival and prognostic factors of women with
      breast cancer in the city of Goiania. METHODS: this is a retrospective, cross
      sectional, observational study that included women with malignant neoplasms of
      the breast identified by the Goiania Population-based Cancer Registry. The
      variables studied were age at diagnosis, tumor size, staging, axillary lymph node
      involvement, tumor grade, disease extent, hormone receptors, and c-erb-B2
      oncoprotein. We performed overall survival analyzes of five and ten years.
      RESULTS: we included 2,273 patients in the study, with an overall survival of
      72.1% in five years and 57.8% in ten years. In the multivariate analysis adjusted
      for tumor size, the factors that influenced the prognosis were axillary lymph
      nodes, histological grade, progesterone receptor, c erb B2, T staging and disease
      extension. CONCLUSION: overall survival in ten years is below that observed in
      other countries, and possibly reflects what happens with the majority of the
      Brazilian population. The prognostic factors found in this population follow the
      same international patterns.

PMID- 29019572
TI  - Epidemiological profile and treatment of substance losses by trauma to the lower
      limbs.
AB  - OBJECTIVES: to evaluate the epidemiological profile, the surgical treatment and
      the postoperative results of patients with complex traumatic injuries to the
      lower limbs. METHODS: we conducted a retrospective study of patients with
      traumatic complex injuries treated by the Plastic Surgery Service of a regional
      hospital in Brasilia. We analyzed clinical-epidemiological data, type of surgical
      procedure and functional recovery of the limb after six months of treatment.
      RESULTS: 119 patients were treated, with a mean age of 29 years, predominantly
      men (76.4%). Motorcycle accident was responsible for most of the injuries, in
      37.8% of cases. The most frequent surgical treatment was skin grafting (62.1%),
      followed by the fasciocutaneous flap (21.9%), muscular flap (12.6%) and
      microsurgical flap (3.4%). Six months after completion of the surgical treatment,
      35.3% of the patients needed crutches to move, characterizing a delay in limb
      functional recovery that, however, was significantly related to the presence of
      fractures, external fixation or bone exposure in the preoperative period.
      CONCLUSION: the profile of the patient with complex traumatic lower limb injury
      was a male, motorcycle accident victim, and grafting was the most used treatment.
      Orthopedic trauma with bone fracture, bone exposure and the presence of external
      fixator were significantly associated with a higher risk of limb functional
      impairment, requiring locomotion crutches after six months of treatment.

PMID- 29019573
TI  - Use of transfer factor in immunosuppressed surgical patients.
AB  - OBJECTIVE : to evaluate the action of Transfer Factor on the immune response of
      patients with malignant neoplasm submitted to surgery, chemotherapy and
      radiotherapy. METHOD: we analyzed the variations of leukocytes, total
      lymphocytes, T-lymphocytes and CD4 counts in 60 patients submitted to
      immunostimulation with a single, daily dose of 0.5mg sublingual Transfer Factor,
      started simultaneously with chemotherapy and/or radiotherapy. RESULTS: there were
      statistically significant increases in the counts of all cell lines studied, more
      pronounced after 12 months of use of the medication. CONCLUSION: the Transfer
      Factor restored immune response and showed no side effects.

PMID- 29019574
TI  - Effects of dimethylsulfoxide and pentoxifylline in the vitality of cutaneous
      flaps in rats.
AB  - OBJECTIVES: to verify the influence of dimethylsulfoxide and pentoxifylline on
      the vitality of cutaneous flaps in rats and the tissue repair process. METHODS:
      were studied 30 Wistar rats, submitting them to a 2cm wide by 8cm long dorsal
      cutaneous flap, of caudal base. We distributed the animals in three groups:
      Control Group (n=10) with application gauze moistened with 0.9% Saline in the
      flap bed for 30 seconds; Dimethylsulfoxide group (n=10), with administration of
      1ml of 5% dimethylsulfoxide divided into five injections of 0.2ml in the
      transition of the flap segments; Pentoxifylline group (n=10), with administration
      of pentoxifylline 20mg/kg, diluted to 1ml and divided into five injections of
      0.2ml in the transition of the flap segments. Drugs were administered
      intraoperatively, in a single dose and subcutaneously. We observed the skin flaps
      for changes in color and texture. On the 10th postoperative day, we checked the
      dimensions of viable and necrotic tissues, followed by excision of the specimen
      for histological analysis. RESULTS: the measurements of length of the viable and
      necrotic tissues between groups showed no differences. Histological analysis
      showed that the Dimethylsulfoxide group presented neovascularization,
      inflammatory infiltrate with leukocytes and more structured conjunctival stroma.
      The Pentoxifylline group showed neovascularization and inflammatory infiltrate,
      with moderate to intense granulation. The control group evolved with a higher
      rate of necrosis in the distal segment. CONCLUSION: dimethylsulfoxide and
      pentoxifylline influenced the vitality of the flap and the tissue repair process.
      However, they did not prevent necrosis macroscopically.

PMID- 29019575
TI  - Colon cancer surgery in patients operated on an emergency basis.
AB  - OBJECTIVE: to study the epidemiological profile of patients with colorectal
      cancer operated on an emergency basis at the Bonsucesso Federal Hospital.
      METHODS: this is a retrospective study of patients operated between January 1999
      and December 2012. We analyzed the following variables: age, gender, clinical
      data, TMN staging, tumor location, survival and types of surgery. RESULTS: we
      evaluated 130 patients in the study period. The most frequent clinical picture
      was intestinal obstruction, in 78% of cases. Intestinal perforation was the
      surgical indication in 15%. The majority (39%) of the patients had advanced TNM
      staging, compared with 27% in the initial stage. There were 39 deaths (30%)
      documented in the period. The most common tumor site was the sigmoid colon (51%),
      followed by the ascending colon (16%). The curative intent was performed in most
      cases, with adjuvant treatment being performed in 40% of the patients. Distant
      metastases were found in 42% of the patients and 10% had documented disease
      recurrence. Disease-free survival at two and five years was 69% and 41%,
      respectively. CONCLUSION: there was a high mortality rate and a low survival rate
      in colorectal cancer patients operated on urgently.

PMID- 29019576
TI  - Development of a laparoscopic training model using a smartphone.
AB  - OBJECTIVE: to develop a model of training in video-surgery, of low cost and that
      uses a smartphone as an image-generating source. METHODS: We developed a 38cm
      high, 40cm wide, 40cm long hexagonal-shaped training box, with a front opening of
      12x8 cm for coupling the smartphone. The internal illumination is made with LED
      lamps and for the support of the smartphone, we used a selfie stick, fixed in the
      upper part of the box, that allows control of height, distance, angulation, and
      the coupling of devices with different formats. We selected 20 undergraduate
      students without previous training in video-surgery, who performed four exercises
      in the box, with assessment of the time and amount of errors in the execution of
      the tasks. Each student completed the training for three consecutive weeks. We
      collected the data in spreadsheets for later analysis. RESULTS: Nineteen students
      completed the training program, with significant improvement in the times and in
      the number of errors. CONCLUSION: the developed model was feasible and promoted
      the acquisition of skills in this group of students. In addition, it presents low
      cost, is portable and uses common equipment, such as smartphones.

PMID- 29019577
TI  - Influence of the colon in liver regeneration of rats submitted to hepatectomy and
      colectomy.
AB  - OBJECTIVE: to evaluate whether colectomy, associated with 70% hepatectomy,
      influences liver regeneration in rats. METHODS: we distributed 18 Wistar rats in
      three groups of six animals each. In group I (sham), we performed laparotomy; In
      group II, colectomy + 70% hepatectomy; In group III, only 70% hepatectomy. On the
      6th postoperative day, we collected blood by cardiac puncture under anesthesia,
      followed by euthanasia. We performed serum dosages of aspartate aminotransferase
      (AST), alanine aminotransferase (ALT), albumin and alkaline phosphatase (AF),
      hepatocyte growth factor (HGF) and transforming growth factor-alpha (TGF-alpha).
      We calculated liver regeneration by the formula: liver weight ratio per 100g body
      weight at the time of euthanasia / liver weight preoperatively projected for 100g
      body weight * 100. RESULTS: ALT and AST levels were significantly lower in group
      II when compared with group III (p<0.001). Albuminemia showed significantly
      higher levels in group II. Levels of HGF and TGF-alpha in group II were
      significantly higher than in group III. The percentage of hepatic regeneration
      was significantly higher in group II than in group III. CONCLUSION: Colectomy
      performed simultaneously with 70% hepatectomy had a positive influence on liver
      regeneration in rats. Further research is needed to reveal the molecular
      mechanisms of this effect and to characterize the colon influence in liver
      physiology.

PMID- 29019578
TI  - Nutritional assessment methods as predictors of postoperative mortality in
      gastric cancer patients submitted to gastrectomy.
AB  - OBJECTIVES: to determine the nutritional evaluation method that best predicts
      mortality in 90 days of patients submitted to gastrectomy for gastric cancer.
      METHODS: we conducted a prospective study with 44 patients with gastric cancer,
      stages II to IIIa, of whom nine were submitted to partial gastrectomy, 34 to
      total gastrectomy, and one to esophago-gastrectomy. All patients were
      nutritionally evaluated through the same protocol, up to 72h after hospital
      admission. The parameters used were Patient-Generated Subjective Global
      Assessment (PGSGA), classical anthropometry, current weight and height,
      percentage of weight loss (%WL) and body mass index (BMI). We also measured the
      thickness of the thumb adductor muscle (TAM) in both hands, dominant hand (TAMD)
      and non-dominant hand (TAMND), as well as the calculated the prognostic
      nutritional index (PNI). The laboratory profile included serum levels of albumin,
      erythrocytes, hemoglobin, hematocrit, leukocytes, and total lymphocytes count
      (TLC). RESULTS: of the 44 patients studied, 29 (66%) were malnourished by the
      subjective method, 15 being grade A, 18 grade B and 11 grade C. Cases with PGSGA
      grade B and TAMD 10.2+/-2.9 mm were significantly associated with higher
      mortality. The ROC curves (95% confidence interval) of both PGSGA and TAMD
      thickness reliably predicted mortality at 30 and 90 days. No laboratory method
      allowed predicting mortality at 90 days. CONCLUSION: PGSGA and the TAMD thickness
      can be used as preoperative parameters for risk of death in patients undergoing
      gastrectomy for gastric cancer.

PMID- 29019579
TI  - Epidemiological study of facial fractures at the Oral and Maxillofacial Surgery
      Service, Santa Casa de Misericordia Hospital Complex, Porto Alegre - RS - Brazil.
AB  - OBJECTIVES: to investigate the incidence and etiology of face trauma with
      diagnosis of facial fracture treated at the Buccomaxillofacial Surgery and
      Traumatology Service of the Santa Casa de Misericordia Hospital Complex in Porto
      Alegre. METHODS: we conducted a cross-sectional, retrospective epidemiological
      study of 134 trauma victims with 153 facial fractures. RESULTS: the male gender
      was the most affected (86.6%) and the incidence was higher in the age group from
      21 to 30 years. The main etiology was assault (38.8%), followed by motor vehicle
      accidents (14.2%), motorcycle accidents (13.4%), falls (9%), road accidents
      (6.7%), sports accidents (5.2%), work accidents (5.2%), firearm injuries (4.5%)
      and cycling accidents (3%). The most frequent fractures were those of the
      zygomatic complex (44.5%), followed by fractures of the mandible (42.5%),
      maxillary bone (5.2%), nasal bones (4.5%) and zygomatic arch (3.3%). CONCLUSION:
      the fractures of the zygomatic complex and the mandible were the ones with the
      highest incidence in the facial traumas, having physical assaults as their main
      cause.

PMID- 29019581
TI  - Observation time and spontaneous resolution of primary phimosis in children.
AB  - OBJECTIVE: to investigate spontaneous resolution rate of a series of patients
      with physiologic phimosis in relation to observation time and presence of
      symptoms. METHODS: retrospective and longitudinal follow-up study of patients
      with physiologic phimosis, that did not apply topic treatment. These patients
      were invited for a new visit for reevaluation, or recent data were obtained by
      chart analysis. Spontaneous resolution rate was determined and statistically
      compared to age, presence of symptoms at first medical visit and time until
      reevaluation. RESULTS: seventy one patients were included. Medium time of
      observation from first visit to reevaluation was 37.4 months. There was
      spontaneous resolution of phimosis in 32 (45%) patients. Children with
      spontaneous resolution were younger at initial diagnosis and were observed during
      a longer period of time. Most asymptomatic patients at first visit presented
      spontaneous resolution. However, it was not possible to stablish a significant
      relationship between presence of symptoms and evolution of physiologic phimosis.
      CONCLUSIONS: time of observation was the main determinant of spontaneous
      resolution of patients with physiologic phimosis, reinforcing the current more
      conservative approach regarding circumcision of those patients.

PMID- 29019580
TI  - Effects of local pressure on cutaneous blood flow in pigs.
AB  - OBJECTIVE: to evaluate the effects of increasing pressures on the cutaneous blood
      flow in the skin of pigs. METHODS: we conducted an experimental study in pigs
      submitted to subcutaneous magnetic implants (n=30). After healing, were applied
      external magnets with varying magnetic forces to the skin, generating
      compression. We evaluated the cutaneous circulation of the skin under compression
      by the Laser Speckle Contrast Imaging (LSCI) technique. We measured the depth of
      the implants by ultrasonography, and applied computational simulations to the
      calculation of the different pressure values, considering the different distances
      between implants and external magnets. RESULTS: nineteen implants presented
      complications. The remaining 11 were submitted to different magnetic compression
      forces and perfusion analysis. Two linear regression models showed an inverse
      correlation between exerted pressure and cutaneous perfusion, with significant
      variation, mainly in the initial pressure increases, of up to 20mmHg. CONCLUSION:
      The main reduction in cutaneous blood flow resulted from initial increases of up
      to 20 mmHg. The results suggest that tissue ischemia can occur even in low
      pressure regimes, which could contribute to the appearance of skin lesions,
      particularly ulcers related to medical devices.

PMID- 29019582
TI  - Ultrasound-guided foam sclerotherapy for severe chronic venous insufficiency.
AB  - Chronic venous insufficiency is characterized by cutaneous alterations caused by
      venous hypertension; in severe forms, it progresses to lower limb ulcers. Lower
      limb varicose veins are the main cause of chronic venous insufficiency, and the
      classic treatment includes surgery and compressive therapy. Minimally invasive
      alternative treatments for varicose veins include new techniques such as venous
      thermal ablation using laser or radiofrequency. The use of different methods
      depends on clinical and anatomical factors. Ultrasound-guided foam sclerotherapy
      is the venous injection of sclerosing foam controlled by Doppler ultrasound.
      Sclerotherapy is very useful to treat varicose veins, and probably, is cheaper
      than other methods. However, until the present, it is the less studied method.

PMID- 29019583
TI  - Management of infected pancreatic necrosis: state of the art.
AB  - Pancreatic necrosis occurs in 15% of acute pancreatitis. The presence of
      infection is the most important factor in the evolution of pancreatitis. The
      diagnosis of infection is still challenging. Mortality in infected necrosis is
      20%; in the presence of organic dysfunction, mortality reaches 60%. In the last
      three decades, there has been a real revolution in the treatment of infected
      pancreatic necrosis. However, the challenges persist and there are many unsolved
      questions: antibiotic treatment alone, tomography-guided percutaneous drainage,
      endoscopic drainage, video-assisted extraperitoneal debridement, extraperitoneal
      access, open necrosectomy? A step up approach has been proposed, beginning with
      less invasive procedures and reserving the operative intervention for patients in
      which the previous procedure did not solve the problem definitively. Indication
      and timing of the intervention should be determined by the clinical course.
      Ideally, the intervention should be done only after the fourth week of evolution,
      when it is observed a better delimitation of necrosis. Treatment should be
      individualized. There is no procedure that should be the first and best option
      for all patients. The objective of this work is to critically review the current
      state of the art of the treatment of infected pancreatic necrosis.

PMID- 29019585
TI  - Educational project: low cost porcine model for venous cutdown training.
AB  - OBJECTIVE: to describe and evaluate the acceptance of a porcine experimental
      model in venous cutdown on a medical education project in Southwest of Brazil.
      METHOD: a porcine experimental model was developed for training in venous cutdown
      as a teaching project. Medical students and resident physicians received
      theoretical training in this surgical technique and then practiced it on the
      model. After performing the procedure, participants completed a questionnaire on
      the proposed model. This study presents the model and analyzes the questionnaire
      responses. RESULTS: the study included 69 participants who used and evaluated the
      model. The overall quality of the porcine model was estimated at 9.16 while the
      anatomical correlation between this and human anatomy received a mean score of
      8.07. The model was approved and considered useful in the teaching of venous
      cutdown. CONCLUSIONS: venous dissection training in porcine model showed good
      acceptance among medical students and residents of this institution. This simple
      and easy to assemble model has potential as an educational tool for its
      resemblance to the human anatomy and low cost.

PMID- 29019584
TI  - A proposal of Brazilian Society of Surgical Oncology (BSSO/SBCO) for
      standardizing cytoreductive surgery (CRS) plus hyperthermic intraperitoneal
      chemotherapy (HIPEC) procedures in Brazil: pseudomixoma peritonei, appendiceal
      tumors and malignant peritoneal mesothelioma
AB  - Cytoreductive surgery plus hypertermic intraperitoneal chemotherapy has emerged
      as a major comprehensive treatment of peritoneal malignancies and is currently
      the standard of care for appendiceal epithelial neoplasms and pseudomyxoma
      peritonei syndrome as well as malignant peritoneal mesothelioma. Unfortunately,
      there are some worldwide variations of the cytoreductive surgery and hypertermic
      intraperitoneal chemotherapy techniques since no single technique has so far
      demonstrated its superiority over the others. Therefore, standardization of
      practices might enhance better comparisons between outcomes. In these settings,
      the Brazilian Society of Surgical Oncology considered it important to present a
      proposal for standardizing cytoreductive surgery plus hypertermic intraperitoneal
      chemotherapy procedures in Brazil, with a special focus on producing homogeneous
      data for the developing Brazilian register for peritoneal surface malignancies.

PMID- 29019586
TI  - Continuous versus interrupted suture technique in microvascular anastomosis in
      rats.
AB  - PURPOSE: To compare the continuous and interrupted suture technique on femoral
      artery on rats after vessel repair and 14 days after. METHODS: Twenty rats were
      operated randomly divided into two group matched according to the suture
      technique used: interrupted or continuous. We performed a femoral anastomosis on
      the right femoral artery. We analyzed weight, arterial caliber, anastomosis time
      and patency after vessel repair and 14 days after. RESULTS: There was no
      significant difference between groups in the weight (p=0.64), diameter of the
      femoral artery (p=0.95) and patency (p=1.00). The time spent in the anastomosis
      was 451 seconds in the continuous group and 718 seconds in the interrupted group,
      presenting significant difference (p<0.01). CONCLUSION: The continuous suture
      technique shows a similar patency rates than interrupted technique, however with
      a shorter time to perform the anastomosis.

PMID- 29019587
TI  - End-to-side versus end-to-end neurorrhaphy at the peroneal nerve in rats.
AB  - PURPOSE: To evaluate three different kinds of neurorrhaphy of the peroneal nerve.
      METHODS: Eigthy rats were divided into 5 groups. Control: nerve had no
      intervention. End-to-end (EE): nerve was cut and elongated with a nerve graft
      with two end-to-end neurorrhaphies. End-to-side (ES): nerve was cut and sutured
      to the graft with at the lateral side of the nerve. Side-to-end (SE): the nerve
      was cut and sutured to the graft with end-to-end neurorrhaphy. Denervated: nerve
      was cut and both endings were buried into the muscle. The evaluation was done by
      walking track analysis, electrophysiology, body mass, cranial tibial muscle mass,
      nerve and muscle fibers morphometry. RESULTS: The EE, ES and SE have the same
      potential of reinnervation. CONCLUSION: There is no functional or histological
      difference between these different types of neurorrhaphy.

PMID- 29019588
TI  - Ultrastructural analysis and residual DNA evaluation of rabbit vein scaffold.
AB  - PURPOSE: To investigate the ultrastructural characteristics and analysis of
      residual DNA in scaffold models, produced with decellularized vena cava in an
      experimental model with rabbits. METHODS: Three groups were created for
      ultrastructural and residual DNA analysis: group 1 - control, consisting of
      samples of vena cava in natura; group 2 - SD, consisting of vein fragments
      submitted to 2% sodium deoxycholate decellularization by shaking (160rpm - Shaker
      News Brunswick Scientific(r)) for 1 hour at controlled temperature shaker at 37
      degrees C; group 3 - SDS, consisting of vein fragments submitted to 1% sodium
      dodecyl sulfate decellularization under the same previous condition, for 2 hours.
      RESULTS: The ultrastructural matrix of the blood vessel maintained its vintegrity
      after either decellularization models. The results of the two quantification
      methods demonstrated a significant decrease in the DNA content of the
      decellularized vena cava samples as compared to the control samples and, differed
      statistically from each other, p <0.05. CONCLUSION: The 2% DS protocol for vein
      decellularization, in this experimental model, was considered the best protocol
      because it presented less amount of residual DNA without causing substantial
      destruction of the extracellular matrix.

PMID- 29019589
TI  - Role of the route of leukotrienes in an experimental model of oral mucositis
      induced by 5-fluorouracil 1.
AB  - PURPOSE: To investigate the participation of cysteinyl leukotrienes in the
      pathophysiology of oral mucositis. METHODS: Oral mucositis was induced in
      hamsters using 5-fluorouracil (5-FU; 60 and 40 mg/kg; i.p., on days 1 and 2,
      respectively, and with excoriations in jugal mucosa on day 4). Montelukast (10,
      20, or 40 mg/kg/d; gavage), MK886 (3 mg/kg/d, i.p.), or saline or celecoxib (7.5
      mg/kg/d; i.p.) was administered 1 h prior to 5-FU and daily, until the fourth
      (MK886) or tenth day, when the animals were euthanized and their jugal mucosa was
      collected for macroscopic, histopathological, and immunohistochemical evaluation.
      RESULTS: Neither montelukast nor MK-886 prevented the oral mucositis induced by 5
      FU, as observed by histopathological evaluation. In addition, we did not find
      significant differences in the expression of inducible nitric oxide synthase-2,
      cyclooxygenase-2, or interleukin (IL)-1beta between the experimental and control
      groups. However, we did observe a significant decrease in tumor necrosis factor
      (TNF)-alpha expression for all doses of montelukast; we also observed a
      significant decrease in IL-10 with 40 mg/kg/d and MK 886. CONCLUSIONS: Cysteinyl
      leukotrienes do not play an important role in experimental oral mucositis induced
      by 5-FU. There is a modulating action specifically on TNF-alpha.

PMID- 29019591
TI  - X-ray dynamic observation of cervical degenerative disease induced by unbalanced
      dynamic and static forces in rats 1.
AB  - PURPOSE: To investigate dynamically the X-ray appearance of cervical degenerative
      disease induced by unbalanced dynamic and static forces in rats. METHODS: A total
      of 60 Sprague Dawley rats were randomized into test (n=45) and control (n=15)
      groups, which were randomly subdivided into the one-, three- and six-month post
      operative groups. The test group included 10, 15 and 20 rats at the respective
      corresponding post-operative stage and the control group included five rats at
      each time-point. By excising cervicodorsal muscles, interspinous ligaments and
      supraspinous ligament of rats in the test group, the balance of dynamic and
      static forces on cervical vertebrae was disrupted to establish a rat model of
      cervical degeneration. Spinal X-ray images were acquired, and intervertebral disc
      space and intervertebral foramen size were measured at one, three and six months
      post-operation. The results were analyzed and compared among groups. RESULTS:
      Cervical dynamic and static imbalance accelerated the appearance of cervical
      degenerative disease on X-ray. CONCLUSION: Cervical degenerative disease may be
      induced by unbalanced dynamic and static forces in rats.

PMID- 29019590
TI  - Schinus terebinthifolius Raddi ( Aroeira) leaves oil attenuates inflammatory
      responses in cutaneous wound healing in mice 1.
AB  - PURPOSE: To investigated the inflammatory, angiogenic and fibrogenic activities
      of the Schinus terebinthifolius Raddi leaves oil (STRO) on wound healing.
      METHODS: The excisional wound healing model was used to evaluate the effects of
      STRO. The mice were divided into two groups: Control, subjected to vehicle
      solution (ointment lanolin/vaseline base), or STRO- treated group, administered
      topically once a day for 3, 7 and 14 days post-excision. We evaluated the
      macroscopic wound closure rate; the inflammation was evaluated by leukocytes
      accumulation and cytokine levels in the wounds. The accumulation of neutrophil
      and macrophages in the wounds were determined by assaying myeloperoxidase and N
      acetyl-beta-D-glucosaminidase activities. The levels of TNF-alpha, CXCL-1 and CCL
      2 in wound were evaluated by ELISA assay. Angiogenesis and collagen fibers
      deposition were evaluated histologically. RESULTS: We observed that macroscopic
      wound closure rate was improved in wounds from STRO-group than Control-group. The
      wounds treated with STRO promoted a reduction in leucocyte accumulation and in
      pro-inflammatory cytokine. Moreover, STRO treatment increased significantly the
      number of blood vessels and collagen fibers deposition, as compared to control
      group. CONCLUSION: Topical application of STRO display anti-inflammatory and
      angiogenic effects, as well as improvement in collagen replacement, suggesting a
      putative use of this herb for the development of phytomedicines to treat
      inflammatory diseases, including wound healing.

PMID- 29019592
TI  - The influence of allopurinol and post-conditioning on lung injuries induced by
      lower-limb ischemia and reperfusion in Wistar rats.
AB  - PURPOSE: To analyze the effects of allopurinol and of post-conditioning on lung
      injuries induced by lower-limb ischemia and reperfusion. METHODS: Thirty rats
      were used. They were divided in 5 groups: (1) group A: abdominal aortic
      dissection only, (2) group B: ischemia and reperfusion, (3) group C: administered
      allopurinol (100mg/Kg) a few hours before procedure, (4) group D: post
      conditioned and (5) group E: administered allopurinol and post-conditioned. With
      the exception of group A, all groups were submitted to infrarenal aortic ischemia
      for 2 hours, and reperfusion for 72 hours. After euthanasia, lungs were removed
      for histological analysis. They were graded under two scores: pulmonary injury
      (neutrophil infiltration, interstitial edema, vascular congestion, and
      destruction of lung architecture) and lymphocytic score (neutrophil infiltration,
      lymphoid aggregate and secondary follicle). RESULTS: On the pulmonary injury
      score, the degree of injury was smaller than in groups D and E, when compared to
      group B, p<0.05. Group C did not obtain the same result (p>0,05). On the
      lymphocytic score, there was no statistic difference among groups, p>0.05.
      CONCLUSION: Both post-conditioning and the combination of allopurinol and post
      conditioning were effective in remote lung protection induced by lower-limbs I/R.
      When used in isolation, allopurinol showed no protective effect.

PMID- 29019593
TI  - Effects of folic acid administration on testicular ischemia/reperfusion injury in
      rats.
AB  - PURPOSE: To determine the effect of folic acid (FA) on experimental testicular
      ischemia/reperfusion (I/R) in rats. METHODS: Sixty male Wistar rats were randomly
      divided into 6 groups. The control group received physiologic saline orally. The
      sham-operated group received physiologic saline orally then exposed to midline
      laparotomy without clamping the IR. The I/R rats received oral gavage of the
      saline then subjected to 1h ischemia /24h reperfusion, period. In folic acid
      (2mg/kg+IR) rats received oral gavage of the FA (2mg/kg) then subjected to 1h
      I/24h R. groups 5-6 received FA (5 and 10 mg/kg), then subjected to 1 h I/24 h,
      respectively. At the end of the study, semen samples were collected for
      spermatozoa characteristics. The left testis was removed for histological
      analysis and superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione
      peroxidase (GPx) measurement. RESULTS: Spermatozoa mobility, mortality (%)
      significantly decreased in I/R group (P<0.05). Dose dependent increase observed
      on spermatozoa mobility, mortality (%) using different levels of the FA (2, 5 and
      10 mg/kg) treated rat (P<0.05). Tissue MDA levels significantly increased in I/R
      rat (P<0.05) while FA (2, 5 and 10mg/kg) in a dose dependent manner decreased I/R
      induced MDA (P<0.05). Experimental I/R significantly decreased SOD and GPx
      activity (P<0.05). Administration of the FA (2, 5 and 10mg/kg) significantly
      increased tissue SOD and GPx activity in I/R rat (P<0.05). Seminiferous tubules
      degenerated and loss of spermatogenesis with few spermatocytes was observed in
      degenerated testis tubules in I/R rat. Orally administration of the FA (5 and 10
      mg/kg) improved testis characteristics with few normal seminiferous tubules and
      spermatocyte in seminiferous tubules in experimental I/R-induced rat. CONCLUSION:
      The treatment of folic acid had a benefit effect against ischemia-reperfusion.

PMID- 29019594
TI  - Allogeneic mesenchymal stem cells and xenogenic platelet rich plasma, associated
      or not, in the repair of bone failures in rabbits with secondary osteoporosis.
AB  - PURPOSE: To assess the efficacy of allogeneic mesenchymal stem cells and
      xenogenic platelet rich plasma in the treatment of bone failure of osteoporotic
      rabbits secondary to estrogenic deprivation and iatrogenic hypercortisolism.
      METHODS: Eight female rabbits underwent ovarian resection and corticoid therapy
      to induce clinical status of osteoporosis. Four failures were produced in the
      tibiae, with each failure being treated with hemostatic sponge, allogenic
      mesenchymal stem cells, xenogenic platelet-rich plasma and the association
      between both. The animals were divided into two groups, evaluated
      radiographically and histopathologically at 30 and 60 days post treatment.
      RESULTS: A radiographically confirmed consolidation of bone failures treated with
      allogeneic mesenchymal stem cells, associated with the histopathological image of
      mature and immature bone tissue, without evidence of osteopenia, was compared
      with the other groups, in which radiolucent failures with osteopenia and fibrosis
      were still present, denoting the satisfactory effect of the first treatment in
      detriment to the others. CONCLUSION: The treatment of bone failures of rabbits
      with secondary osteoporosis with allogeneic mesenchymal stem cells induced
      greater bone consolidation with mature and immature bone tissue production
      (p<0.01), when compared to the other treatments.

PMID- 29019595
TI  - Effects of local alendronate administration on bone defect healing.
      Histomorphometric and radiological evaluation in a rabbit model.
AB  - PURPOSE: To performed a histomorphometric and radiological study to evaluate the
      effects of alendronate sodium administered locally in mandibular bone defects
      created in rabbits. METHODS: Two circular defects 5 mm in diameter were created
      bilaterally in the mandibular corpus of 20 New Zealand rabbits (i.e., four
      defects per animal). Each defect received one of four treatments: no treatment
      (EC group), alendronate irrigation (AL group), autogenous bone grafting (AG
      group), or alendronate irrigation with autogenous bone grafting (AL+AG group).
      Histomorphometric and radiological assessments were conducted at 4 and 8 weeks
      after surgery. RESULTS: Between-group comparisons of the new bone area, the value
      of the AL+AG group was significantly lower thanthe remaining three groups at 4
      weeks postoperatively. In all groups, the new bone area was significantly larger
      at 8 weeks than at 4 weeks. The residual graft area at 4 and 8 weeks was
      significantly higher in the AL+AG group than in the AG group, although it was
      significantly smaller at 8 weeks than at 4 weeks in both these groups.
      CONCLUSION: The use of alendronate sodium in conjunction with autogenous bone
      grafting improves the osteoconductive properties of the graft, enhances graft
      retention in the defect, and improves ossification.

PMID- 29019596
TI  - Our journal on the 25th International Congress of History of Science and
      Technology.

PMID- 29019597
TI  - The botanist George Gardner and his impressions of slave culture in Brazil: Rio
      de Janeiro, 1810-1850.
AB  - This article analyzes the English botanist George Gardner's trip to Brazil during
      the 1830s. After graduating from the University of Glasgow Gardner was influenced
      by his teacher and by readings of contemporary naturalists and set off for Brazil
      in March of 1836, arriving two months later in Rio de Janeiro. The article
      presents Gardner's impressions of slavery in Brazil, in an attempt to unveil the
      symbolic universe of a play he witnessed and described, which took place on a
      farm in Rio de Janeiro on Christmas night. By describing black slavery in its
      routes across the Atlantic, we compare this event with other similar happenings
      in Brazil and in Trinidad and Tobago.

PMID- 29019598
TI  - The evolutionist debate in Spain during the nineteenth century: a re-examination.
AB  - This article re-examines the research on evolutionism in Spain and updates
      knowledge on this topic in light of the work of Thomas Glick, the more
      philosophical work of Diego Nunez and contributions in recent years from the
      Latin American network of historians of biology and evolution, who have dealt
      with the more polemical aspects of the reception of evolution theory. It includes
      new arguments, such as identification of the drawings in El Museo Universal,
      whose Lamarckian or Darwinian nature has been a subject of ongoing debate. It
      also covers the crucial role of the acceptance of Haeckel's work in Spain in
      comparison to the weaker support for a strictly Darwinian perspective, the role
      of the Spanish histology school, and the impact of evolutionism on literature.

PMID- 29019599
TI  - The thalidomide tragedy: the struggle for victims' rights and improved
      pharmaceutical regulation.
AB  - The thalidomide tragedy in the late 1950s was a watershed moment for
      pharmaceutical regulation. New uses for this medication are being researched and
      implemented today. This article revisits the history of thalidomide and its
      consequences for regulation and for victims' rights in Brazil, based on a
      literature review, documentary analysis, and newspaper reports. The events
      highlighted herein show the lack of strong standards for safe medication use, as
      well as how the tragedy was transformed into a public problem through its
      divulgation in the press; the article also shows that the increasing mobilization
      of victims was essential in pushing for more effective drug regulations.

PMID- 29019600
TI  - The evaluation of scientific productivity.
AB  - The paper examines the evaluation of scientific productivity. It analyzes the
      metrification of the evaluation of scientific production, as well as the
      historical construction, and current uses of scientific evaluation. It argues
      that this process contains a paradox: the more that metrics become impersonal,
      the less they are recognized by scientists. The study is divided into five
      sections: contextualization of the problematics of scientific evaluation; a
      description of the main stages in the institutionalization of metrification; an
      overview of the development of the main evaluation indexes; some examples of the
      application of these indexes; and analytical consequences and recommendations for
      the formulation of a new evaluation agenda.

PMID- 29019601
TI  - Negotiating boundaries: Encyclopedie, romanticism, and the construction of
      science.
AB  - Natural history in the eighteenth and nineteenth centuries has been widely
      debated in the field of the social sciences. This paper explores the social
      negotiation of boundaries in the Encyclopedie and romantic science. Highlighting
      the importance of imagination and aesthetics to the scientific realms, we
      perceive a different comprehension of the scientific field through the empirical
      study of how scientific demarcation is constructed. Works by Erasmus Darwin,
      Goethe, and Humboldt illustrate how reliable science was performed through
      atypical scientific methods. After pointing out the links between literary,
      artistic, and scientific works, we then debate a series of changes that framed
      the scientific imagery of romantic and encyclopaedic sciences.

PMID- 29019602
TI  - ["New plants that scholars do not know:" scientific exploration of nature in
      Portuguese East Asia, 1768-1808].
AB  - As Portugal lost most of its conquests to the Dutch, Portuguese East Asia was
      reduced to the remaining trading posts (feitorias) and Brazil became the center
      of attention for colonial policies. Consequently, during the eighteenth century
      the Portuguese crown did not express greater interest in developing native
      Eastern knowledge of nature. These interests were tied to goals involving
      reconfiguration of the economy of the Brazilian colonies. The idea to cultivate
      economically important Eastern species such as pepper, nutmeg, cinnamon, cloves,
      teak, and sandalwood in Brazil took shape, but was not immediately successful.
      This article examines this attempt to extend Portugal's scientific network to the
      East, as well as the process of transplanting these species.

PMID- 29019603
TI  - [The influence of Naturphilosophie in nineteenth-century science:
      electromagnetism and energy].
AB  - Phenomena involving electromagnetism and conservation of energy during the
      nineteenth century did not fit the reigning Newtonian paradigm. Among scholars,
      there was the need to explain such facts considering "something more" that had
      not yet been expressed. Through this explanation, Naturphilosophie, the
      philosophical branch associated with the German romantic movement of the
      nineteenth century, seems to offer new ways of understanding the sciences. In
      this article, we present main aspects of the work of Schelling, the main exponent
      of Naturphilosophie, and how his assumptions were inserted into the physical
      sciences to explain electromagnetism and conservation of energy.

PMID- 29019604
TI  - [Pangenesis, genes, epigenesis].
AB  - In 1868, Darwin published his book The variation of animals and plants under
      domestication, which laid out his theory of heredity. This included the
      assumption that development was essential to understanding the evolutionary
      process. This present article reassesses the Darwinian theory of pangenesis in
      order to revisit its historical value. The conclusion is that the theory of
      pangenesis was well-suited to its time, and additionally, reflections of this
      assumption can be found in work in new areas known as evolutionary biology of
      development (evo-devo) and epigenetics.

PMID- 29019605
TI  - [The aesthetics of degeneration and expressions of the alienated: readings from
      Julio Dantas at the Rilhafoles Hospital].
AB  - The proposal of this article is to briefly present how artistic expressions of
      the alienated appear as a discursive element in medical and critical readings of
      Julio Dantas, starting with his thesis, Pintores e poetas de Rilhafolles, which
      he presented in 1900 as the conclusion to his medicine course in Lisbon. This
      particularly involves investigating the methods Dantas used in his invested and
      conceptual propositions on this topic, considering that his interests responded
      to very specific issues: the characteristics and forms of social degeneration.
      The article also reviews some of the reverberations in the social and artistic
      environments that were insulted by the publication of the thesis.

PMID- 29019606
TI  - [Medicine is a joke: humorous depictions of physicians in the Santuario da
      Trindade newspaper].
AB  - This article analyzes representations of medical knowledge in Goias in the early
      decades of the twentieth century through anecdotes and articles in the Catholic
      newspaper Santuario da Trindade, which circulated from 1922 to 1931. The
      anecdotes reflect a certain distancing from the modernization of medicine and
      ridicule medical science, demonstrating what Bakhtin characterized as the
      irreverence of popular culture in relation to serious institutions. On the other
      hand, medical knowledge was greatly esteemed in the paper's articles, and served
      to legitimize the moralizing discourse of its editors. Therefore, in the same
      newspaper this knowledge was simultaneously represented respectfully and mocked,
      revealing the complexity of how changes in medical practices during the period
      were absorbed.

PMID- 29019607
TI  - [European representations of birth control and abortions in Islamic societies and
      harems in the modern period].
AB  - Throughout the modern period, Islamic women (whether they lived in palaces or
      normal houses) resorted to measures to prevent conception or to induce abortion
      when pregnancy occurred. They used herbs and abortifacient drugs or relied on
      help from other women to eliminate unwanted pregnancies. Such practices were
      recorded by Europeans - in some cases, doctors - who traveled to Islamic regions
      and described these scenes in their narratives. In addition to abortions,
      infanticide was also observed in the imperial palaces. Here we discuss how these
      sources described birth control, and how they investigated the lascivious harem,
      a recurring trope in orientalist literature, from a medical perspective.

PMID- 29019608
TI  - International expositions: a historiographic approach from Latin America.
AB  - This essay examines the historiography of international exhibitions, seen as
      geopolitical phenomena of modernity to which are associated the rise of middle
      classes, nationalist and colonialist movements, as well as an exhibitionary
      network connecting distinct spaces and times. Most of the recent studies analyses
      this repertoire and this pattern, and their relationship with political,
      economic, social and cultural issues. This study stresses, among ongoing
      approaches, the Latin American work - still barely visible or integrated into a
      field which is already consolidated -, and suggests how its visibility can be
      improved.

PMID- 29019609
TI  - [A reading of gender: representations of normality in the magazine Vamos Ler!,
      1936-1948].
AB  - This research note is the result of an investigation into the circulation of
      normality as a category of mental health among the lay population. Based on the
      hypothesis that the appropriation of discourse from medical categories is marked
      by a polyphony of meanings and not by homogeneity, this project analyzed the
      variety magazine Vamos Ler! (1936-1948), which featured active participation by
      its readers in correspondence sections. The subjectivity contained in the letters
      published in the magazine reveals that the medical discourse was not hegemonic in
      the lay definition of normality, emphasizing the presence of other discourses
      (including the experiences of individual readers) which assumed the condition of
      truth in constructing representations of normal men and women.

PMID- 29019610
TI  - On "Colonial scientific-medical documentary films and the legitimization of an
      ideal state in post-war Spain," or the importance of being cited.

PMID- 29019611
TI  - On the right to not cite, and not being deceivingly lynched and libeled because
      of it.

PMID- 29019613
TI  - Uncommon cause of dyspnoea after percutaneous closure of the left atrial
      appendage.

PMID- 29019612
TI  - Unveiling transthyretin cardiac amyloidosis and its predictors among elderly
      patients with severe aortic stenosis undergoing transcatheter aortic valve
      replacement.
AB  - Aims: Transthyretin cardiac amyloidosis (ATTR-CA) has been reported in patients
      with aortic stenosis (AS) but its prevalence and phenotype are not known. We
      examine elderly patients with severe symptomatic AS undergoing transcatheter
      aortic valve replacement (TAVR) and determine the prevalence and phenotype of
      ATTR-CA non-invasively. Methods and results: We performed technetium-99m
      pyrophosphate (99mTc-PYP) cardiac scintigraphy prospectively on patients who
      underwent TAVR, to screen for ATTR-CA. Transthoracic echocardiography and speckle
      strain imaging were performed. We assessed the association of several parameters
      with ATTR-CA using multivariable logistic regression and constructed receiver
      operating curves to evaluate the best predictors of ATTR-CA. Among 151 patients
      (mean age 84 +/- 6 years, 68% men), 16% (n = 24) screened positive for ATTR-CA
      with 99mTc-PYP scintigraphy. Compared with patients without ATTR-CA, ATTR-CA
      patients had a thicker interventricular septum (1.3 vs. 1.1 cm, P = 0.007),
      higher left ventricular (LV) mass index (130 vs. 98 g/m2, P = 0.002), and lower
      stroke volume index (30 vs. 36 mL/m2, P = 0.009). ATTR-CA patients had advanced
      diastolic dysfunction with higher E/A ratio (2.3 vs. 0.9, P = 0.001) and lower
      deceleration time (176 vs. 257 ms, P < 0.0001); impairment in systolic function
      with lower ejection fraction (48% vs. 56%, P = 0.011), myocardial contraction
      fraction (26 vs. 41, P < 0.0001), and average of lateral and septal mitral
      annular tissue Doppler S' (4.0 vs. 6.6 cm/s, P < 0.0001). While ATTR-CA patients
      had more impaired global longitudinal strain (-12 vs. -16%, P = 0.007), relative
      apical longitudinal strain was the same regardless of ATTR-CA diagnosis (0.98 vs.
      0.98, P = 0.991). Average S' best predicted ATTR-CA in multivariable logistic
      regression (odds ratio 16.67 per 1 cm/s decrease with AUC 0.96, 95% confidence
      interval 0.90-0.99, P = 0.002) with a value <=6 conferring 100% sensitivity for
      predicting a positive 99mTc-PYP amyloid scan. Conclusions: Transthyretin cardiac
      amyloidosis is prevalent in 16% of patients with severe calcific AS undergoing
      TAVR and is associated with a severe AS phenotype of low-flow low-gradient with
      mildly reduced ejection fraction. Average tissue Doppler mitral annular S' of < 6
      cm/s may be a sensitive measure that should prompt a confirmatory 99mTc-PYP scan
      and subsequent testing for ATTR-CA. Prospective assessment of outcomes after TAVR
      is needed in patients with and without ATTR-CA.

PMID- 29019616
TI  - Dangerous relationships: aortic stenosis and transthyretin cardiac amyloidosis.

PMID- 29019614
TI  - Associations of serum potassium levels with mortality in chronic heart failure
      patients.
AB  - Aims: Medication prescribed to patients suffering from chronic heart failure
      carries an increased risk of impaired potassium homeostasis. We examined the
      relation between different levels of serum potassium and mortality among patients
      with chronic heart failure. Methods and results: From Danish National registries,
      we identified 19 549 patients with a chronic heart failure diagnosis who had a
      measurement of potassium within minimum 90 days after initiated medical treatment
      with loop diuretics and angiotensin converting enzyme inhibitors or angiotensin
      II receptor blockers. All-cause mortality was examined according to eight
      predefined potassium levels: 2.8-3.4 mmol/L, 3.5-3.8 mmol/L, 3.9-4.1 mmol/L, 4.2
      4.4 mmol/L, 4.5-4.7 mmol/L, 4.8-5.0 mmol/L, 5.1-5.5 mmol/L, and 5.6-7.4 mmol/L.
      Follow-up was 90 days from potassium measurement. We estimated the risk of all
      cause mortality using multivariable adjusted Cox proportional hazard model, with
      normal serum potassium level at 4.2-4.4 mmol/L as reference. After 90 days, the
      mortality in the eight strata was 14.4, 8.0, 6.3, 5.0, 5.8, 7.9, 10.3, and 21.1%
      respectively. In multivariable adjusted analysis, patients with potassium levels
      of 2.8-3.4 mmol/L [hazard ratio (HR): 3.16; confidence interval (CI): 2.43-4.11],
      3.5-3.8 mmol/L (HR: 1.62; CI: 1.31-1.99), 3.9-4.1 mmol/L (HR: 1.29; CI: 1.08
      1.55), 4.8-5.0 mmol/L (HR: 1.34; CI: 1.10-1.63), 5.1-5.5 mmol/L (HR: 1.60; CI:
      1.29-1.97), and 5.6-7.4 mmol/L (HR: 3.31; CI: 2.61-4.20) had an increased risk of
      all-cause mortality. Conclusion: Levels within the lower and upper levels of the
      normal serum potassium range (3.5-4.1 mmol/L and 4.8-5.0 mmol/L, respectively)
      were associated with a significant increased short-term risk of death in chronic
      heart failure patients. Likewise, potassium below 3.5 mmol/L and above 5.0 mmol/L
      was also associated with increased mortality.

PMID- 29019617
TI  - Serum potassium in patients with chronic heart failure: once we make a U-turn
      where should we go?

PMID- 29019615
TI  - Haemodynamic profiles of children with end-stage heart failure.
AB  - Aims: To evaluate associations between haemodynamic profiles and symptoms, end
      organ function and outcome in children listed for heart transplantation. Methods
      and results: Children <18 years listed for heart transplant between 1993 and 2013
      with cardiac catheterization data [pulmonary capillary wedge pressure (PCWP),
      right atrial pressure (RAP), and cardiac index (CI)] in the Pediatric Heart
      Transplant Study database were included. Outcomes were New York Heart Association
      (NYHA)/Ross classification, renal and hepatic dysfunction, and death or clinical
      deterioration while on waitlist. Among 1059 children analysed, median age was 6.9
      years and 46% had dilated cardiomyopathy. Overall, 58% had congestion (PCWP >15
      mmHg), 28% had severe congestion (PCWP >22 mmHg), and 22% low cardiac output (CI
      < 2.2 L/min/m2). Twenty-one per cent met the primary outcome of death (9%) or
      clinical deterioration (12%). In multivariable analysis, worse NYHA/Ross
      classification was associated with increased PCWP [odds ratio (OR) 1.03, 95%
      confidence interval (95% CI) 1.01-1.07, P = 0.01], renal dysfunction with
      increased RAP (OR 1.04, 95% CI 1.01-1.08, P = 0.007), and hepatic dysfunction
      with both increased PCWP (OR 1.03, 95% CI 1.01-1.06, P < 0.001) and increased RAP
      (OR 1.09, 95% CI 1.06-1.12, P < 0.001). There were no associations with low
      output. Death or clinical deterioration was associated with severe congestion (OR
      1.6, 95% CI 1.2-2.2, P = 0.002), but not with CI alone. However, children with
      both low output and severe congestion were at highest risk (OR 1.9, 95% CI 1.1
      3.5, P = 0.03). Conclusion: Congestion is more common than low cardiac output in
      children with end-stage heart failure and correlates with NYHA/Ross
      classification and end-organ dysfunction. Children with both congestion and low
      output have the highest risk of death or clinical deterioration.

PMID- 29019618
TI  - What can haemodynamic profiles teach us about heart failure in the paediatric
      population?

PMID- 29019620
TI  - John McMurray MD FESC.

PMID- 29019619
TI  - Special issues in heart failure: pulmonary hypertension, deranged potassium
      levels, and haemodynamic profiles.

PMID- 29019621
TI  - Heartfailurematters.org.

PMID- 29019622
TI  - The Geoffrey Rose Lecture 2017.

PMID- 29019623
TI  - Andrew Hurst Henderson, 1930-2017.

PMID- 29019624
TI  - The ESC Textbook of Vascular Biology.

PMID- 29019625
TI  - Holger Thiele MD.

PMID- 29019626
TI  - The Challenges of Caring for Children with Special Health Care Needs: Pain
      Assessment and Team-Based Care.

PMID- 29019627
TI  - Dry Drowning: Myths and Misconceptions.
AB  - Drowning is a leading cause of death in children and is highly preventable. More
      than 10 people die of drowning in the United States each day, most of them
      adults. Rates of drowning are highest in children given their developmental
      vulnerabilities. Drowning incidents that result in cardiopulmonary arrest have a
      straightforward emergency clinical response, but the management approaches to the
      more common scenario of brief, nonfatal submersion is less clear. Clinicians must
      make clinical-care decisions based on evidence to provide safe and effective care
      in a timely manner and to help families avoid unnecessary anxiety. Such anxiety
      has been heightened by reports of unanticipated "dry drowning" appearing in the
      media. This article discusses this concept and provides guidance for clinicians.
      [Pediatr Ann. 2017;46(10):e354-e357.].

PMID- 29019628
TI  - Health Care Disparities Among Children with Special Health Care Needs.

PMID- 29019629
TI  - Health Disparities and Child Development After Prematurity.
AB  - There is increased recognition that preterm neonates require sequential
      surveillance to capture the spectrum of coordination, communication, learning,
      and behavior regulation disorders that may occur in the first 5 years of life and
      beyond. In particular, the framework of follow-up needs to go beyond the
      detection of cerebral palsy, blindness, and deafness in the first 2 years of life
      for only those at highest preterm risk (ie, <28 weeks gestation, with
      combinations of severe cranial sonographic abnormalities, bronchopulmonary
      dysplasia, and retinopathy of prematurity). In addition, there are numerous
      barriers for diverse families in accessing quality, comprehensive early
      intervention and early child education supports. This article highlights recent
      research on the long-term impact of preterm birth with a focus on disparities in
      resource access and in outcomes at entry to kindergarten and early educational
      trajectories. Across all degrees of prematurity, children from disadvantaged
      backgrounds face significant disparities both in access to comprehensive and
      continuous supports and in long-term academic outcomes. Ten key recommendations
      are provided for ensuring proactive management strategies for the long-term
      academic, behavioral, and social success of these at-risk children. [Pediatr Ann.
      2017;46(10):e360-e364.].

PMID- 29019630
TI  - Prolonged Hospital Discharge for Children with Technology Dependency: A Source of
      Health Care Disparities.
AB  - Children with ventilator assistance have been supported in living at home since
      1981 when parental advocacy ushered in a change to Medicaid policy. As the
      population of children who use medical technology such as long-term ventilation
      increases, we must critically evaluate our systems for preparing families for
      home life. Discharge delays persist in the modern era because of fragmentation
      between hospital and home systems. These discharge delays result in children
      spending time in less developmentally rich environments, further exacerbating the
      health and development disparities of children with complex disabilities. In this
      article, we discuss the complication of hospital discharge and how it contributes
      to health and developmental disparities. We also describe a hospital-to-home
      transitional care model, which presents a home-like environment to provide
      developmental support while focusing on parental training, home nursing, and
      public-funding arrangements. [Pediatr Ann. 2017;46(10):e365-e370.].

PMID- 29019631
TI  - Disparities in Life Course Outcomes for Transition-Aged Youth with Disabilities.
AB  - Close to 750,000 youth with special health care needs transition to adult health
      care in the United States every year; however, less than one-half receive
      transition-planning services. Using the "F-words" organizing framework, this
      article explores life course outcomes and disparities in transition-aged youth
      with disabilities, with a special focus on youth with autism, Down syndrome, and
      cerebral palsy. Despite the importance of transition, a review of the available
      literature revealed that (1) youth with disabilities continue to have poor
      outcomes in all six "F-words" domains (ie, function, family, fitness, fun,
      friends, and future) and (2) transition outcomes vary by race/ethnicity and
      disability. Professionals need to adopt a holistic framework to examine
      transition outcomes within a broader social-ecological context, as well as
      implement evidence-based transition practices to help improve postsecondary
      outcomes of youth with disabilities. [Pediatr Ann. 2017;46(10):e371-e376.].

PMID- 29019632
TI  - Racial and Ethnic Health Disparities and Trauma-Informed Care for Children
      Exposed to Community Violence.
AB  - Racial and ethnic disparities in health outcomes and access have been
      consistently documented for a wide variety of physical and behavioral health
      conditions. Health inequities are most pronounced in areas with high levels of
      racial and ethnic segregation, where children and adolescents are also more
      likely to face economic inequality, which places them at high risk for exposure
      to neighborhood violence and traumatic loss. Community violence exposure (CVE)
      has been increasingly recognized as a prominent contributor to negative physical
      and mental health outcomes. CVE has been linked to children's risk for negative
      psychological outcomes, such as posttraumatic stress disorder, externalizing
      behavior, and internalizing symptoms, as well as obesity, asthma, and health-risk
      behaviors. Providers of pediatric care have opportunities to address CVE and
      related health disparities by developing trauma-informed systems that routinely
      screen for CVE, provide basic support for affected families, and link those in
      need to trauma-focused intervention. [Pediatr Ann. 2017;46(10):e377-e381.].

PMID- 29019633
TI  - Behavioral Health Disparities Among Children and Youth with Special Health Care
      Needs.
AB  - The burden of mental health morbidity, disability, and mortality in children is
      not equally distributed across populations in the United States. The consequence
      is widespread differences in health status between certain groups of children
      that result in systematic behavioral health disparities. In the US, an estimated
      12.8% of children (9.4 million) have a special health care need. Mental,
      emotional, and behavioral problems and disorders are widespread among children
      and youth with special health care needs (CYSHCN), but are often undetected and
      untreated despite the adverse consequences to children throughout the life
      course. CYSHCN experience behavioral health disparities in the prevalence of
      behavioral health problems and conditions, and in the access to needed services.
      Further investigation is required to fully identify behavioral health needs, the
      mechanisms contributing to the disparities, and effective strategies to prevent
      and provide interventions for CYSHCN. Investing in research and interventions is
      vital to reducing behavioral health disparities. [Pediatr Ann. 2017;46(10):e382
      e386.].

PMID- 29019635
TI  - Subpoenas and Law Enforcement Requests for Patient Information.

PMID- 29019634
TI  - Pain Assessment in Newborns, Infants, and Children.
AB  - Pain in children is underestimated and undertreated because of lack of pain
      assessment tools. Pain assessment depends on the cognitive development of the
      child being tested, clinical context, and pain typology. For children older than
      age 6 years, pain assessment is based on a self-report. For children younger than
      age 6 years, behavioral pain scales are needed to assess pain. Numerous pain
      scales exist. Many are reliable and some are recommended, but all have specific
      conditions for their use. In this article, we review the available pain scales
      for children from birth to adolescence. We provide the validity criteria of each
      pain scale to help caregivers use the adapted tools. We then propose a synthesis
      of the reliable tools to use based on the pain context. [Pediatr Ann.
      2017;46(10):e387-e395.].

PMID- 29019636
TI  - Dr. Bob. Going Viral: Getting the Bugs Out of Your Travel Plans.

PMID- 29019638
TI  - Spine Conditions: Foreword.

PMID- 29019640
TI  - Spine Conditions: Mechanical and Inflammatory Low Back Pain.
AB  - Mechanical low back pain (LBP) is an injury or derangement of an anatomic
      structure in the low back. When evaluating patients with LBP, clinicians should
      maintain clinical suspicion for vertebral fracture, cancer, and cauda equina
      syndrome. Management includes patient education focused on exercise, massage, and
      behavioral approaches such as cognitive behavioral therapy. Acupuncture can be an
      effective alternative and specific herbal supplements may provide short-term pain
      relief. The prognosis for patients with mechanical LBP is good. Inflammatory LBP
      is pain resulting from a systemic inflammatory condition, often referred to as
      axial spondyloarthritis. Ankylosing spondylitis is chronic inflammatory LBP
      characterized by early onset (mean age 24 years), with a higher prevalence in
      men. Five clinical parameters can help identify inflammatory LBP: improvement
      with exercise, pain at night, insidious onset, onset at younger than 40 years,
      and no improvement with rest. Management of inflammatory LBP typically includes
      nonsteroidal anti-inflammatory drugs and structured exercise programs, with
      emphasis on the involvement of a rheumatology subspecialist. Spondyloarthritis is
      associated with other rheumatic or autoimmune conditions, including rheumatoid
      arthritis, inflammatory bowel disease, and psoriasis. These should be considered
      when evaluating patients with inflammatory LBP.

PMID- 29019639
TI  - Spine Conditions: Cervical Spine Conditions.
AB  - There are a variety of causes of neck pain, including trauma and degenerative
      changes. The history of onset helps to direct evaluation, including the need for
      imaging or ancillary testing. Patterns of pain, weakness, and other specific
      physical examination findings also aid in diagnosis. Management of most soft
      tissue injuries involves early mobilization, whereas fractures are managed based
      on patterns of instability. Acute spinal cord injury requires emergent care, to
      include possible decompressive surgery. The role of hypothermia and
      corticosteroids in these patients remains unclear. Cervical radiculopathy (eg,
      disk herniation, arthritic changes) can be managed conservatively in most
      patients. Central cord compression, or myelopathy, often is overlooked but is a
      common condition among older patients. Although certain patients may benefit from
      surgery, many have a stable course or slow progression that can be managed
      nonsurgically. Rheumatoid arthritis can have significant effects on the cervical
      spine. Patients with inflammatory conditions may improve with steroids,
      nonsteroidal anti-inflammatory drugs, or biologic drugs, but these drugs rarely
      have lasting benefit in degenerative conditions. Stretching, strengthening, and
      other physical therapy modalities have been shown to be helpful for patients with
      chronic and acute but stable neck conditions.

PMID- 29019641
TI  - Spine Conditions: Lumbar Spinal Stenosis.
AB  - Lumbar spinal stenosis (LSS) is a frequent cause of chronic low back and lower
      extremity pain in older patients. Symptomatic LSS typically is described as
      neurogenic claudication consisting of pain, weakness, numbness, and/or fatigue
      arising in the back and radiating into the buttock, thigh, or lower leg. The
      diagnosis is complicated by lack of reliable clinical or x-ray criteria. North
      American Spine Society guidelines recommend magnetic resonance imaging study
      without contrast to confirm anatomic narrowing of the spinal canal or nerve root
      impingement. Conservative management options include exercise and drug therapy.
      Epidural injections can be considered for temporary symptom management. No
      studies show greater effectiveness of surgical intervention over conservative
      management in patients with mild to moderate symptoms. Progressive symptoms,
      emergence of frank neurologic deficit, or findings consistent with cauda equina
      syndrome are indications to pursue surgical evaluation. Decompression surgery
      without fusion typically is recommended in the absence of spondylolisthesis or
      other spinal instability. Active rehabilitation is likely more effective than
      usual care for improvement in functional status within 12 months postoperatively
      without adverse events. Approximately one-third to one-half of patients with mild
      to moderate LSS symptoms may have a favorable prognosis.

PMID- 29019642
TI  - Spine Conditions: Occupational Spine Conditions.
AB  - Neck and back conditions have significant effects on employee health and
      productivity. More than $7 billion in lost revenue in the United States annually
      can be attributed to workplace back pain among employees ages 40 to 65 years.
      According to the Bureau of Labor Statistics, in 2012 back pain was the most
      prevalent musculoskeletal condition resulting in workplace absenteeism. The
      incidence of these conditions is higher among individuals in certain professions,
      such as bus drivers, police officers, and correctional officers. Risk factors
      include obesity, depression, nicotine dependence, and alcohol abuse. There is
      limited evidence about whether modifying risk factors decreases the incidence of
      neck and back conditions. Specific efforts to reduce the burden in the workplace
      have shown mixed results. Use of simple interventions, such as braces and
      orthotics, has not consistently shown benefit. In addition, limited data show
      minimal or no evidence of effective prevention or management with back school
      programs and instruction on lifting techniques. The most consistent data support
      regular exercise as a method to prevent back pain. However, attempts to include
      exercise in workplace activities have shown mixed results. Lower rates of
      workplace absenteeism have been show to result from employee education on these
      issues.

PMID- 29019643
TI  - Skeletal Diversity in Combinatorial Fashion: A New Format for the Castagnoli
      Cushman Reaction.
AB  - A new format for the Castagnoli-Cushman reaction of structurally diverse
      dicarboxylic acids, amines, and aldehydes in the presence of acetic anhydride as
      dehydrating agent is described. The reaction is distinctly amenable to parallel
      format: the combinatorial array of 180 reactions delivered 157 products of >85%
      purity without chromatographic purification (of this number, 143 compounds had
      >94% purity). The new method offers a convenient preparation of the skeletally
      and peripherally diverse, lead- and druglike gamma- and delta-lactam carboxylic
      acids with high diastereoselectivity in combinatorial fashion.

PMID- 29019644
TI  - Charge Transport Limitations in Perovskite Solar Cells: The Effect of Charge
      Extraction Layers.
AB  - Understanding the charge transport characteristics and their limiting factors in
      organolead halide perovskites is of great importance for the development of
      competitive and economically advantageous photovoltaic systems derived from these
      materials. In the present work, we examine the charge carrier mobilities in
      CH3NH3PbI3 (MAPI) thin films obtained from a one-step synthesis procedure and in
      planar n-i-p devices based on these films. By performing time-of-flight
      measurements, we find mobilities around 6 cm2/V s for electrons and holes in MAPI
      thin films, whereas in working solar cells, the respective effective mobility
      values are reduced by 3 orders of magnitude. From complementary experiments on
      devices with varying thicknesses of electron and hole transport layers, we
      identify the charge extraction layers and the associated interfaces rather than
      the perovskite material itself as the major limiting factors of the charge
      carrier transport time in working devices.

PMID- 29019647
TI  - 126 264 Assigned Chemical Formulas from an Atmospheric Pressure Photoionization
      9.4 T Fourier Transform Positive Ion Cyclotron Resonance Mass Spectrum.
AB  - Here, we present atmospheric pressure photoionization (APPI) Fourier transform
      ion cyclotron resonance (FTICR) mass analysis of a volcanic asphalt sample by
      acquiring data for 20 Da wide mass segments across a 1000 Da range, stitched into
      a single composite mass spectrum, and compare to a broad-band mass spectrum for
      the same sample. The segmented spectrum contained 170 000 peaks with magnitude
      greater than 6sigma of the root-mean-square (rms) baseline noise, for which 126
      264 unique elemental compositions could be assigned. Approximately two-thirds of
      those compositions represent monoisotopic (i.e., chemically different) species.
      That complexity is higher than that for any previously reported mass spectrum and
      almost 3 times greater than that obtained from the corresponding broad-band
      spectrum (59 015). For the segmented mass spectrum, the signal-to-noise ratio
      (S/N) was significantly higher throughout the spectrum, but especially at the
      lower and upper ends of mass distribution relative to that of the near-Gaussian
      broad-band mass distribution. Despite this S/N improvement, mass measurement
      accuracy was noticeably improved only at lower masses. The increased S/N did,
      however, yield a higher number of peaks and higher dynamic range throughout the
      entire segmented spectrum relative to the conventional broad-band spectrum. The
      additional assigned peaks include higher heteroatom species, as well as
      additional radicals and isotopologues. Segmenting can require a significant
      investment in data acquisition and analysis time over broad-band spectroscopy
      (~1775% in this case) making it best suited for targeted analysis and/or when
      complete compositional coverage is important. Finally, the present segmented
      spectrum contains, to our knowledge, more assigned peaks than any spectrum of any
      kind (e.g., UV-vis, infrared, microwave, magnetic resonance, etc.).

PMID- 29019646
TI  - Noncanonical Roles of Lipids in Different Cellular Fates.
AB  - Lipids are a diverse class of biomolecules. The biosynthesis and transport of
      these molecules are controlled by a considerable number of proteins, which
      facilitate spatiotemporal regulation of lipids during different fundamental
      cellular processes. Although lipids are traditionally considered as molecules for
      energy storage and as structural components of membranes, they are being
      increasingly recognized for their signaling roles. There is a growing
      appreciation of lipids' chemical diversity, which approaches that of proteins. In
      this Perspective, we discuss recent studies that suggest novel functions for
      distinct lipid species during different cellular processes. In particular, we
      discuss findings from our laboratory that illuminate the involvement of
      ceramides, polyunsaturated triacylglycerols, and very long chain fatty acids in
      different cellular fates. We also highlight recent innovative methods that have
      enabled the recognition of previously unknown lipid classes and/or roles of these
      molecules in different biological processes. We envision that advances in lipid
      identification, visualization, and perturbation will pave the way for broader
      investigations into this fascinating and influential class of biomolecules.

PMID- 29019645
TI  - Multimodality of Structural, Electrical, and Gravimetric Responses of
      Intercalated MXenes to Water.
AB  - Understanding of structural, electrical, and gravimetric peculiarities of water
      vapor interaction with ion-intercalated MXenes led to design of a multimodal
      humidity sensor. Neutron scattering coupled to molecular dynamics and ab initio
      calculations showed that a small amount of hydration results in a significant
      increase in the spacing between MXene layers in the presence of K and Mg
      intercalants between the layers. Films of K- and Mg-intercalated MXenes exhibited
      relative humidity (RH) detection thresholds of ~0.8% RH and showed monotonic RH
      response in the 0-85% RH range. We found that MXene gravimetric response to water
      is 10 times faster than their electrical response, suggesting that H2O-induced
      swelling/contraction of channels between MXene sheets results in trapping of H2O
      molecules that act as charge-depleting dopants. The results demonstrate the use
      of MXenes as humidity sensors and infer potential impact of water on structural
      and electrical performance of MXene-based devices.

PMID- 29019648
TI  - Atmospheric Pressure Drift Tube Ion Mobility-Orbitrap Mass Spectrometry: Initial
      Performance Characterization.
AB  - Atmospheric pressure drift tube ion mobility spectrometry (AP-DTIMS) was coupled
      with Fourier transform Orbitrap mass spectrometry. The performance capabilities
      of this versatile new arrangement were demonstrated for different DTIMS ion
      gating operation modes and Orbitrap mass spectrometer parameters with regard to
      sensitivity and resolving power. Showcasing the optimized AP-DTIMS-Orbitrap MS
      system, isobaric peptide and sugar isomers were successfully resolved and the
      identities of separated species validated by high-energy collision dissociation
      experiments.

PMID- 29019649
TI  - Dietary Fatty Acids Control the Species of N-Acyl-Phosphatidylethanolamines
      Synthesized by Therapeutically Modified Bacteria in the Intestinal Tract.
AB  - Engineering the gut microbiota to produce specific beneficial metabolites
      represents an important new potential strategy for treating chronic diseases. Our
      previous studies with bacteria engineered to produce N-acyl
      phosphatidylethanolamines (NAPEs), the immediate precursors of the lipid satiety
      factors N-acyl-ethanolamides (NAEs), found that colonization of these bacteria
      inhibited development of obesity in C57BL/6J mice fed a high fat diet. Individual
      NAE species differ in their bioactivities. Intriguingly, colonization by our
      engineered bacteria resulted in increased hepatic N-stearoyl-ethanolamide
      (C18:0NAE) levels despite the apparent inability of these bacteria to
      biosynthesize its precursor N-stearoyl-phosphatidylethanolamine (C18:0NAPE) in
      vitro. We therefore sought to identify the factors that allowed C18:0NAPE
      biosynthesis by the engineered bacteria after colonization of the intestinal
      tract. We found that the species of NAPE biosynthesized by engineered bacteria
      depends on the species of dietary fatty acids available in the intestine,
      suggesting a simple method to fine-tune the therapeutic effects of modified
      microbiota.

PMID- 29019650
TI  - Desalination and Nanofiltration through Functionalized Laminar MoS2 Membranes.
AB  - Laminar membranes of two-dimensional materials are excellent candidates for
      applications in water filtration due to the formation of nanocapillaries between
      individual crystals that can exhibit a molecular and ionic sieving effect, while
      allowing high water flux. This approach has been exemplified previously with
      graphene oxide, however these membranes suffer from swelling when exposed to
      liquid water, leading to low salt rejection and reducing their applicability for
      desalination applications. Here, we demonstrate that by producing thin (~5 MUm)
      laminar membranes of exfoliated molybdenum disulfide (MoS2) in a straightforward
      and scalable process, followed by a simple chemical functionalization step, we
      can efficiently reject ~99% of the ions commonly found in seawater, while
      maintaining water fluxes significantly higher (~5 times) than those reported for
      graphene oxide membranes. These functionalized MoS2 membranes exhibit excellent
      long-term stability with no swelling and consequent decrease in ion rejection,
      when immersed in water for periods exceeding 6 months. Similar stability is
      observed when exposed to organic solvents, indicating that they are ideal for a
      variety of technologically important filtration applications.

PMID- 29019651
TI  - Combining Machine Learning and Nanofluidic Technology To Diagnose Pancreatic
      Cancer Using Exosomes.
AB  - Circulating exosomes contain a wealth of proteomic and genetic information,
      presenting an enormous opportunity in cancer diagnostics. While microfluidic
      approaches have been used to successfully isolate cells from complex samples,
      scaling these approaches for exosome isolation has been limited by the low
      throughput and susceptibility to clogging of nanofluidics. Moreover, the analysis
      of exosomal biomarkers is confounded by substantial heterogeneity between
      patients and within a tumor itself. To address these challenges, we developed a
      multichannel nanofluidic system to analyze crude clinical samples. Using this
      platform, we isolated exosomes from healthy and diseased murine and clinical
      cohorts, profiled the RNA cargo inside of these exosomes, and applied a machine
      learning algorithm to generate predictive panels that could identify samples
      derived from heterogeneous cancer-bearing individuals. Using this approach, we
      classified cancer and precancer mice from healthy controls, as well as pancreatic
      cancer patients from healthy controls, in blinded studies.

PMID- 29019652
TI  - Strong Carrier-Phonon Coupling in Lead Halide Perovskite Nanocrystals.
AB  - We highlight the importance of carrier-phonon coupling in inorganic lead halide
      perovskite nanocrystals. The low-temperature photoluminescence (PL) spectrum of
      CsPbBr3 has been investigated under a nonresonant and a nonstandard, quasi
      resonant excitation scheme, and phonon replicas of the main PL band have been
      identified as due to the Frohlich interaction. The energy of longitudinal optical
      (LO) phonons has been determined from the separation of the zero phonon band and
      phonon replicas. We reason that the observed LO phonon coupling can only be
      related to an orthorhombically distorted crystal structure of the perovskite
      nanocrystals. Additionally, the strength of carrier-phonon coupling has been
      characterized using the ratio between the intensities of the first phonon replica
      and the zero-phonon band. PL emission from localized versus delocalized carriers
      has been identified as the source of the observed discrepancies between the LO
      phonon energy and phonon coupling strength under quasi-resonant and nonresonant
      excitation conditions, respectively.

PMID- 29019653
TI  - Development of a Terpenoid-Production Platform in Streptomyces reveromyceticus SN
      593.
AB  - Terpenoids represent the largest class of natural products, some of which are
      resources for pharmaceuticals, fragrances, and fuels. Generally, mass production
      of valuable terpenoid compounds is hampered by their low production levels in
      organisms and difficulty of chemical synthesis. Therefore, the development of
      microbial biosynthetic platforms represents an alternative approach. Although
      microbial terpenoid-production platforms have been established in Escherichia
      coli and yeast, an optimal platform has not been developed for Streptomyces
      species, despite the large capacity to produce secondary metabolites, such as
      polyketide compounds. To explore this potential, we constructed a terpenoid
      biosynthetic platform in Streptomyces reveromyceticus SN-593. This strain is
      unique in that it harbors the mevalonate gene cluster enabling the production of
      furaquinocin, which can be controlled by the pathway specific regulator Fur22. We
      simultaneously expressed the mevalonate gene cluster and subsequent terpenoid
      biosynthetic genes under the control of Fur22. To achieve improved fur22 gene
      expression, we screened promoters from S. reveromyceticus SN-593. Our results
      showed that the promoter associated with rvr2030 gene enabled production of 212
      +/- 20 mg/L botryococcene to levels comparable to those previously reported for
      other microbial hosts. Given that the rvr2030 gene encodes for an enzyme involved
      in the primary metabolism, these results suggest that optimized expression of
      terpenoid-biosynthetic genes with primary and secondary metabolism might be as
      important for high yields of terpenoid compounds as is the absolute expression
      level of a target gene(s).

PMID- 29019655
TI  - Quantum Chemical Modeling of Cycloaddition Reaction in a Self-Assembled Capsule.
AB  - Dispersion-corrected density functional theory is used to study the cycloaddition
      reaction between phenyl acetylene and phenyl azide inside a synthetic, self
      assembled capsule. The capsule is first characterized computationally and a
      previously unrecognized structure is identified as being the most stable. Next,
      an examination of the free energies of host-guest complexes is conducted,
      considering all possible reagent, solvent, and solvent impurity combinations as
      guests. The experimentally observed relative stabilities of host-guest complexes
      are quite well reproduced, when the experimental concentrations are taken into
      account. Experimentally, the presence of the host capsule has been shown to
      accelerate the cycloaddition reaction and to yield exclusively the 1,4
      regioisomer product. Both these observations are reproduced by the calculations.
      A detailed energy decomposition analysis shows that reduction of the entropic
      cost of bringing together the reactants along with a geometric destabilization of
      the reactant supercomplex are the major contributors to the rate acceleration
      compared to the background reaction. Finally, a sensitivity analysis is conducted
      to assess the stability of the results with respect to the choice of methodology.

PMID- 29019656
TI  - Adsorption of Insecticidal Crystal Protein Cry11Aa onto Nano-Mg(OH)2: Effects on
      Bioactivity and Anti-Ultraviolet Ability.
AB  - The traditional Bacillus thuringiensis (Bt) formulations for field applications
      are not resistant to harsh environmental conditions. Hence, the active
      ingredients of the Bt bioinsecticides could degrade quickly and has low anti
      ultraviolet ability in the field, which significantly limits its practical
      application. In the present study, we developed an efficient and stable delivery
      system for Bt Cry11Aa toxins. We coated Cry11Aa proteins with Mg(OH)2
      nanoparticles (MHNPs), and then assessed the effects of MHNPs on bioactivity and
      anti-ultraviolet ability of the Cry11Aa proteins. Our results indicated that
      MHNPs, like "coating clothes", could effectively protect the Cry protein and
      enhance the insecticidal bioactivity after UV radiation (the degradation rate was
      decreased from 64.29% to 16.67%). In addtion, MHNPs could improve the proteolysis
      of Cry11Aa in the midgut and aggravate the damage of the Cry protein to the gut
      epithelial cells, leading to increased insecticidal activity against Culex
      quinquefasciatus. Our results revealed that MHNPs, as an excellent nanocarrier,
      could substantially improve the insecticidal bioactivity and anti-ultraviolet
      ability of Cry11Aa.

PMID- 29019654
TI  - Transition-Metal-Free Radical C(sp3)-C(sp2) and C(sp3)-C(sp3) Coupling Enabled by
      2-Azaallyls as Super-Electron-Donors and Coupling-Partners.
AB  - The past decade has witnessed the rapid development of radical generation
      strategies and their applications in C-C bond-forming reactions. Most of these
      processes require initiators, transition metal catalysts, or organometallic
      reagents. Herein, we report the discovery of a simple organic system (2-azaallyl
      anions) that enables radical coupling reactions under transition-metal-free
      conditions. Deprotonation of N-benzyl ketimines generates semistabilized 2
      azaallyl anions that behave as "super-electron-donors" (SEDs) and reduce aryl
      iodides and alkyl halides to aryl and alkyl radicals. The SET process converts
      the 2-azaallyl anions into persistent 2-azaallyl radicals, which capture the aryl
      and alkyl radicals to form C-C bonds. The radical coupling of aryl and alkyl
      radicals with 2-azaallyl radicals makes possible the synthesis of functionalized
      amine derivatives without the use of exogenous radical initiators or transition
      metal catalysts. Radical clock studies and 2-azaallyl anion coupling studies
      provide mechanistic insight for this unique reactivity.

PMID- 29019657
TI  - trans-10,cis-12-Conjugated Linoleic Acid Affects Expression of Lipogenic Genes in
      Mammary Glands of Lactating Dairy Goats.
AB  - The molecular mechanisms on milk fat depression (MFD) in response to trans-10,cis
      12-conjugated linoleic acid (t10,c12-CLA) supplementation in ruminants were
      elucidated in this research with dairy goats. A total of 30 2-year-old Xinong
      Saanen dairy goats [40 +/- 5 days in milk (DIM)] at peak lactation stage were
      assigned to a 3 * 3 Latin square design (14 day treatment period, followed with
      14 day washout). Three CLA treatments included (a) control, fed the basal diet
      only without CLA supplementation; (b) orally supplemented with 8 g/day of lipid
      encapsulated CLA (low dose, CLA-1); and (c) orally supplemented with 16 g/day of
      lipid-encapsulated CLA (high dose, CLA-2). Expression levels of fatty acid
      metabolism genes in the mammary tissues were analyzed by real-time quantitative
      polymerase chain reaction (RT-qPCR) in three goats on day 1 and the other three
      goats on day 14 in each group after the discontinuation of CLA treatment in the
      third experimental period. Dietary supplementation of CLA led to a significant
      decrease of milk fat compared to the control (p < 0.05). Milk fat concentrations
      in CLA-1 and CLA-2 groups were 2.74 and 2.42%, respectively, while the milk fat
      concentration in the control group was 2.99%. Decreases in short- and medium
      chain fatty acids (<16 carbons) and increases in unsaturated fatty acids were
      observed in the CLA-2 group (p < 0.05). The desaturation indexes of C16 and C18
      fatty acids were obviously increased (p < 0.01). RT-qPCR results revealed
      decreases of the mRNA expression levels of SREBF1, PPARG, LPL, CD36, FABP3,
      ACSL1, FASN, ACACA, DGAT2, TIP47, ADRP, and BTN1A1 genes in mammary glands (p <
      0.05) and an increase of the SCD gene because of CLA supplementation (p < 0.05).
      In conclusion, t10,c12-CLA-induced MFD was possibly the result from the
      downregulation of genes involved in lipogenesis in goat mammary glands.

PMID- 29019658
TI  - Resonance Enhancement of Nonlinear Optical Scattering in Monolayer-Protected Gold
      Clusters.
AB  - Monolayer-protected metal clusters (MPCs) have recently gained significant
      research interest, since they are promising candidates for various applications
      in bioimaging and catalysis. Besides this, MPCs promise to aid in understanding
      the evolution of the metallic state from bottom-up principles. MPCs can be
      prepared with atomic precision, and their nonscalable properties (indicating
      molecule-like behavior) have been studied with a variety of techniques both
      theoretically and experimentally. Here, we present spectrally resolved second
      order nonlinear optical scattering experiments on thiolate-protected gold
      clusters (Au130(SR)50, Au144(SR)60, and Au500(SR)120). The three clusters share
      common resonance enhancement around 490 nm, which is ascribed to an interband
      transition. This indicates emerging metal-like properties, and we tentatively
      assign the onset of metal-like behavior somewhere between 102 and 130 gold atoms.

PMID- 29019659
TI  - Effect of Extended Conjugation of N-Heterocyclic Carbene-Based Sensitizers on the
      Performance of Dye-Sensitized Solar Cells.
AB  - We report the synthesis, characterization, and photovoltaic properties of four
      ruthenium complexes (CI101, CBTR, CB111, and CB108) having various N-heterocyclic
      carbene ancillary ligands, pyridine-imidazole, -benzimidazole, 
      dithienobenzimidazole, and -phenanthroimidazole, respectively. These complexes
      were designed to investigate the effect of extended conjugation ordained from
      ring fusion on the power conversion efficiencies of the solar cells. The device
      sensitized by CB108, the pyridine-phenanthroimidazole conjugated complex, showed
      an improved efficiency (9.89%) compared to those of pyridine-benzimidazole
      conjugated system (CBTR, 9.72%) and the parent unfused ring system (CI101,
      6.24%). Surprisingly, the sulfur-incorporated pyridine-dithienobenzimidazole
      system (CB111, 9.24%) exhibited a little lower efficiency than that of N719
      (9.41%). The enhanced photovoltaic performance of CB108 was mainly attributed to
      the increase in electron lifetime and diffusion length confirmed by the
      electrochemical impedance spectroscopy.

PMID- 29019661
TI  - Venlafaxine in Embryos Stimulates Neurogenesis and Disrupts Larval Behavior in
      Zebrafish.
AB  - Venlafaxine, a widely prescribed antidepressant, is a selective serotonin and
      norepinephrine reuptake inhibitor in humans, and this drug is prevalent in
      municipal wastewater effluents. While studies have shown that this drug affects
      juvenile fish behavior, little is known about the developmental impact on
      nontarget aquatic animals. We tested the hypothesis that venlafaxine deposition
      in the egg, mimicking maternal transfer of this antidepressant, disrupts
      developmental programming using zebrafish (Danio rerio) as a model. Embryos (1-4
      cell stage) were microinjected with either 1 or 10 ng venlafaxine, which led to a
      rapid reduction (90%) of this drug in the embryo at hatch. There was a
      concomitant increase in the concentration of the major metabolite o
      desmethylvenlafaxine during the same period. Embryonic exposure to venlafaxine
      accelerated early development, increased hatching rate and produced larger larvae
      at 5 days post fertilization. Also, there was an increase in neuronal birth in
      the hypothalamus, dorsal thalamus, posterior tuberculum, and the preoptic region,
      and this corresponded with a higher spatial expression of nrd4, a key marker of
      neurogenesis. The venlafaxine-exposed larvae were less active and covered shorter
      distance in a light and dark behavioral test compared to the controls. Overall,
      zygotic exposure to venlafaxine disrupts early development, including brain
      function, and compromises larval behavior, suggesting impact of this drug on
      developmental programming in zebrafish.

PMID- 29019662
TI  - Exceptionally High Electric Double Layer Capacitances of Oligomeric Ionic
      Liquids.
AB  - Electric double layer (EDL) capacitors are promising as next-generation energy
      accumulators if their capacitances and operation voltages are both high. However,
      only few electrolytes can simultaneously fulfill these two requisites. Here we
      report that an oligomeric ionic liquid such as IL4TFSI with four imidazolium ion
      units in its structure provides a wide electrochemical window of ~5.0 V, similar
      to monomeric ionic liquids. Furthermore, electrochemical impedance measurements
      using Au working electrodes demonstrated that IL4TFSI exhibits an exceptionally
      high EDL capacitance of ~66 MUF/cm2, which is ~6 times as high as those of
      monomeric ionic liquids so far reported. We also found that an EDL-based field
      effect transistor (FET) using IL4TFSI as a gate dielectric material and SrTiO3 as
      a channel material displays a very sharp transfer curve with an enhanced carrier
      accumulation capability of ~64 MUF/cm2, as determined by Hall-effect
      measurements.

PMID- 29019660
TI  - Antitumor Activity of a Unique Polymer That Incorporates a Fluorescent Self
      Assembled Metallacycle.
AB  - Despite the well-known anticancer activity of mono- and multinuclear platinum
      complexes, studies of the antitumor performances of platinum-based supramolecular
      coordination complexes are rare. Herein, we report on the synthesis of a four
      armed amphiphilic copolymer, Pt-PAZMB-b-POEGMA, containing a metallacycle M, in
      which the tetraphenylethene derivative acts as an aggregation-induced emissive
      fluorescent probe for live cell imaging and the 3,6-bis[trans
      Pt(PEt3)2]phenanthrene (PhenPt) is an anticancer drug. This copolymer was further
      self-assembled into nanoparticles of different sizes and vesicles depending upon
      the experimental conditions. The impacts of the morphology and size of the
      assemblies on their endocytic pathways, uptake rates, internalization amounts,
      and cytotoxicities were investigated. The self-assemblies were further employed
      to encapsulate doxorubicin (DOX) to achieve a synergistic anticancer effect.
      Controlled drug release was also realized via amphiphilicity changes and was
      driven by a glutathione-induced cascade elimination reaction. The DOX-loaded
      nanoparticles of around 50 nm in size exhibited an excellent antitumor
      performance as well as a low systemic toxicity, due to an enhanced permeability
      and retention effect.

PMID- 29019663
TI  - Tracking the Transformation of Nanoparticulate and Ionic Silver at
      Environmentally Relevant Concentration Levels by Hollow Fiber Flow Field-Flow
      Fractionation Coupled to ICPMS.
AB  - It is a great challenge to monitor the physical and chemical transformation of
      nanoparticles at environmentally relevant concentration levels, mainly because
      the commonly used techniques like dynamic light scattering and transmission
      electron microscopy are unable to characterize and quantify trace level
      nanoparticles in complex matrices. Herein, we demonstrate the on-line coupled
      system of hollow fiber flow field-flow fractionation (HF5), minicolumn
      concentration, and inductively coupled plasma mass spectrometry (ICPMS) detection
      as an efficient approach to study the aggregation and chemical transformation of
      silver nanoparticles (AgNPs) and ionic Ag species in the aqueous environment at
      ng/mL levels. Taking advantage of the in-line dialysis of HF5, the selective
      capture of Ag(I) species by the resin in minicolumn, and the high selectivity and
      sensitivity of ICPMS detection, we recorded the aggregation of 10 ng/mL AgNPs in
      complex matrices (e.g., NOM, Na+/Ca2+), revealing an interesting tiny AgNPs
      formation process of photoreduction of trace level Ag(I) that is different from
      larger AgNPs generated at high concentration of Ag(I) by accurate
      characterization and respectively identifying and quantifying new thiol-complexed
      Ag(I) and residual Ag(I) in the intertransformation of Ag(I) and AgNPs in
      domestic wastewater by simultaneously detecting the S and Ag signals via ICPMS.

PMID- 29019664
TI  - Solution-Like Behavior of Photoswitchable Spiropyrans Embedded in Metal-Organic
      Frameworks.
AB  - 1,3,3-Trimethylindolino-6'-nitrobenzopyrylospiran (SP-1) as an example of a
      photoswitchable spiropyran was loaded into the pores of different prototypical
      metal-organic frameworks, namely MOF-5, MIL-68(In), and MIL-68(Ga), by a vapor
      phase process. The successful incorporation in the pores of the MOF was proven by
      X-ray powder diffraction, and the amount of the embedded photoswitchable guest
      was determined by X-ray photoelectron spectroscopy and elemental analysis. In
      contrast to the sterically hindered crystalline state, SP-1 embedded in solid MOF
      hosts shows photoswitching under irradiation with UV light from the spiropyran to
      its merocyanine form with a nearly complete photoisomerization. Switching can be
      reversed by heat treatment. These switching properties were confirmed by means of
      UV/vis and IR spectroscopy. Remarkably, the embedded guest molecules show
      photoswitching and absorption properties similar to those in the dissolved state,
      so that MOFs might be considered as "solid solvents" for photoswitchable
      spiropyrans. In contrast to that, embedment of SP-1 in the smaller pores of MIL
      53(Al) was not successful. SP-1 is mainly adsorbed on the surfaces of the MIL
      53(Al) particles, which also leads to photoswitching properties.

PMID- 29019665
TI  - Effect of Donor Groups on the Performance of Cyclometalated Ruthenium Sensitizers
      in Dye-Sensitized Solar Cells.
AB  - Three new tris-heteroleptic complexes of ruthenium(II) were designed by
      coordinating the metal center with cyclometalating, anchoring, and auxiliary
      ligands with different donor substituents. N-Hexylcarbazole, N
      hexylphenothiazine, and N-hexyldiphenylamine donor moieties were used as
      substituents on the auxiliary ligands for SA633, SA634, and SA635, respectively.
      Complexes were characterized by 1H and 13C 2D-COSY NMR techniques. These
      complexes provide power conversion efficiencies in the range of 7.6-8.2% when
      they are employed in state of the art dye-sensitized solar cells (DSCs) with
      cobalt electrolyte. Various electrochemical and transient techniques were used to
      unveil the unexpected differences in the performance of these very similar
      sensitizers.

PMID- 29019666
TI  - Airborne Methane Emission Measurements for Selected Oil and Gas Facilities Across
      California.
AB  - We report 65 individual measurements of methane emissions from 24 oil and gas
      facilities across California. Methane emission rates were estimated using in situ
      methane and wind velocity measurements from a small aircraft by a novel Gauss'
      Theorem flux integral approach. The estimates are compared with annual mean
      emissions reported to the U.S. Environmental Protection Agency (USEPA) and the
      California Air Resources Board (CARB) through their respective greenhouse gas
      reporting programs. The average emissions from 36 measurements of 10 gas storage
      facilities were within a factor of 2 of emissions reported to USEPA or CARB,
      though large variance was observed and the reporting database did not contain all
      of the facilities. In contrast, average emissions from 15 measurements of the
      three refineries were roughly an order of magnitude more than reported to the
      USEPA or CARB. The remaining measurements suggest compressor emissions are
      variable and perhaps slightly larger than reported, and emissions from one oil
      production facility were roughly concordant with a separate (not GHG reporting)
      bottom-up estimate from other work. Together, these results provide an initial
      facility-specific survey of methane emissions from California oil and natural gas
      infrastructure with observed variability suggesting the need for expanded
      measurements in the future.

PMID- 29019667
TI  - Mixture Toxicity of Nickel and Microplastics with Different Functional Groups on
      Daphnia magna.
AB  - In recent years, discarded plastic has become an increasingly prevalent pollutant
      in aquatic ecosystems. These plastic wastes decompose into microplastics, which
      pose not only a direct threat to aquatic organisms but also an indirect threat
      via adsorption of other aquatic pollutants. In this study, we investigated the
      toxicities of variable and fixed combinations of two types of microplastics [one
      coated with a carboxyl group (PS-COOH) and the other lacking this functional
      group (PS)] with the heavy metal nickel (Ni) on Daphnia magna and calculated
      mixture toxicity using a toxic unit model. We found that toxicity of Ni in
      combination with either of the two microplastics differed from that of Ni alone.
      Furthermore, in general, we observed that immobilization of D. magna exposed to
      Ni combined with PS-COOH was higher than that of D. magna exposed to Ni combined
      with PS. Collectively, the results of our study indicate that the toxic effects
      of microplastics and pollutants may vary depending on the specific properties of
      the pollutant and microplastic functional groups, and further research on the
      mixture toxicity of various combinations of microplastics and pollutants is
      warranted.

PMID- 29019668
TI  - Application of Targeted Metabolomics to Investigate Optimum Growing Conditions to
      Enhance Bioactive Content of Strawberry.
AB  - A simple, sensitive, and rapid assay based on liquid chromatography coupled to
      tandem mass spectrometry was designed for simultaneous quantitation of secondary
      metabolites in order to investigate the influence of variety and agronomic
      conditions on the biosynthesis of bioactive compounds in strawberry. For this
      purpose, strawberries belonging to three varieties with different sensitivity to
      environmental conditions ('Camarosa', 'Festival', 'Palomar') were grown in a
      soilless system under multiple agronomic conditions (electrical conductivity,
      substrate type, and coverage). Targeted metabolomic analysis of polyphenolic
      compounds, combined with advanced chemometric methods based on learning machines,
      revealed significant differences in multiple bioactives, such as chlorogenic
      acid, ellagic acid rhamnoside, sanguiin H10, quercetin 3-O-glucuronide, catechin,
      procyanidin B2, pelargonidin 3-O-glucoside, cyanidin 3-O-glucoside, and
      pelargonidin 3-O-rutinoside, which play a pivotal role in organoleptic properties
      and beneficial healthy effects of these polyphenol-rich foods.

PMID- 29019669
TI  - Synthesis of 2,2-Difluorinated 4-Isoflavanols/4-Thioisoflavanols via a Base
      Catalyzed [4 + 2] Annulation Reaction of gem-Difluoroolefins.
AB  - DBU-catalyzed sequential intermolecular and intramolecular nucleophilic addition
      reactions between gem-difluoroolefins and o-hydroxy/mercapto benzaldehydes have
      been developed to provide a [4 + 2] annulation strategy for facile synthesis of
      gem-difluorinated isoflavanol derivatives. The competitive addition-elimination
      reaction of gem-difluoroolefins with nucleophiles was avoided under mild
      conditions, affording 2,2-difluorinated 4-isoflavanols or 2,2-difluoriated 4
      thioisoflavanols in good to excellent yields.

PMID- 29019671
TI  - Deep Learning Based Regression and Multiclass Models for Acute Oral Toxicity
      Prediction with Automatic Chemical Feature Extraction.
AB  - Median lethal death, LD50, is a general indicator of compound acute oral toxicity
      (AOT). Various in silico methods were developed for AOT prediction to reduce
      costs and time. In this study, we developed an improved molecular graph encoding
      convolutional neural networks (MGE-CNN) architecture to construct three types of
      high-quality AOT models: regression model (deepAOT-R), multiclassification model
      (deepAOT-C), and multitask model (deepAOT-CR). These predictive models highly
      outperformed previously reported models. For the two external data sets
      containing 1673 (test set I) and 375 (test set II) compounds, the R2 and mean
      absolute errors (MAEs) of deepAOT-R on the test set I were 0.864 and 0.195, and
      the prediction accuracies of deepAOT-C were 95.5% and 96.3% on test sets I and
      II, respectively. The two external prediction accuracies of deepAOT-CR are 95.0%
      and 94.1%, while the R2 and MAE are 0.861 and 0.204 for test set I, respectively.
      We then performed forward and backward exploration of deepAOT models for deep
      fingerprints, which could support shallow machine learning methods more
      efficiently than traditional fingerprints or descriptors. We further performed
      automatic feature learning, a key essence of deep learning, to map the
      corresponding activation values into fragment space and derive AOT-related
      chemical substructures by reverse mining of the features. Our deep learning
      architecture for AOT is generally applicable in predicting and exploring other
      toxicity or property end points of chemical compounds. The two deepAOT models are
      freely available at http://repharma.pku.edu.cn/DLAOT/DLAOThome.php or
      http://www.pkumdl.cn/DLAOT/DLAOThome.php .

PMID- 29019670
TI  - Design, Synthesis, and Biological Activities of Vibsanin B Derivatives: A New
      Class of HSP90 C-Terminal Inhibitors.
AB  - Previously, vibsanin B (ViB) was found to preferentially target HSP90beta
      compared to HSP90alpha. In this study, multiple experiments, including pull-down
      assays of biotin-ViB with recombinant HSP90beta-NTD, MD, CTD, and full-length
      HSP90beta, molecular docking of ViB and its derivatives to the HSP90 CTD, and a
      inhibition assay of interaction of the HSP90beta CTD with GST-tagged cyclophilin
      40 (Cyp40) by ViB derivatives, suggest that ViB can directly bind to the HSP90 C
      terminus. On the basis of the docking predictions and primary structure-activity
      relationships (SARs), a series of ViB analogues devised with focus on the C18
      position, along with compounds derivatized at the C4, C7, and C8 positions, were
      designed and chemically synthesized. Compound 12f (IC50 = 1.12 MUM against SK-BR
      3) exhibits great potency with drug-like properties. Overall, our findings
      demonstrate that compounds with the vibsanin B scaffold are a new class of HSP90
      C-terminal inhibitors with considerable potential as anticancer agents.

PMID- 29019672
TI  - Synthesis of Furo[2,3-c]pyridazines via Tandem Transition-Metal Catalysis.
AB  - A general and efficient catalytic approach to synthesis of the furo[2,3
      c]pyridazine ring system is reported. Building on the easily accessible 2-bromo-3
      aminopyridizinone skeleton, a tandem Sonogashira coupling-cycloisomerization
      provides ready access to functionalized furopyridazines. A wide functional group
      tolerance was observed in the tandem reaction, which proceeds in high yield in 1
      3 h. The structure of the heterocyclic ring system was confirmed through single
      crystal X-ray crystallography.

PMID- 29019673
TI  - Molecular Mechanism of Self-Assembly of Aromatic Oligoamides into Interlocked
      Double-Helix Foldamers.
AB  - Foldamer, inspired by the structures and functions of biopolymers, is defined as
      an artificial molecular architecture that can fold into a three-dimensional
      structure in solution and has been a growing and active field in supramolecular
      chemistry. The central issue in foldamer science is to understand how the primary
      sequence of oligomer folds into conformationally ordered structures as well as
      how individual subunits self-associate into assembly. For duplex structures,
      these two issues are always interrelated and inseparable with each other.
      Although the emergence of new foldamer keeps growing, the detailed mechanism
      remains elusive. On the basis of an artificially synthesized arylamide oligoamide
      foldamer with its crystal structure available, we constructed a set of four
      foldamers with a similar backbone but different substituents and aimed at
      dissecting the folding and self-association mechanisms of a double-helical
      foldamer with computations. Using molecular simulations at a microsecond time
      scale, we observed very consistent processes of the spontaneous self-assembly of
      two single-helical motifs into an entwined complex. Our results reveal that
      aggregation of two single-helical motifs driven by extensive pi-pi interactions
      is energetically favorable and that this spontaneous self-assembly proceeds
      through an "unwinding-threading-rewinding" mechanism. The detailed mechanisms
      about the folding and self-assembly in an aromatic oligoamide foldamer we present
      here disclose how the sequence is associated with a well-ordered three
      dimensional structure at atomic level and therefore may have implications for
      designing new foldamers with versatile functions.

PMID- 29019674
TI  - Zn(OTf)2-Catalyzed Phosphinylation of Propargylic Alcohols: Access to gamma
      Ketophosphine Oxides.
AB  - The first facile and efficient Zn(OTf)2-catalyzed direct coupling of unprotected
      propargylic alcohols with arylphosphine oxides has been developed, affording a
      general, one-step approach to access structurally diverse gamma-ketophosphine
      oxides via sequential Meyer-Schuster rearrangement/phospha-Michael reaction along
      with new C(sp3)-P and C?O bond formations, operational simplicity, and complete
      atom economy under ligand-free and base-free conditions.

PMID- 29019676
TI  - Small Molecule Antagonists of the Interaction between the Histone Deacetylase 6
      Zinc-Finger Domain and Ubiquitin.
AB  - Inhibitors of HDAC6 have attractive potential in numerous cancers. HDAC6
      inhibitors to date target the catalytic domains, but targeting the unique zinc
      finger ubiquitin-binding domain (Zf-UBD) of HDAC6 may be an attractive
      alternative strategy. We developed X-ray crystallography and biophysical assays
      to identify and characterize small molecules capable of binding to the Zf-UBD and
      competing with ubiquitin binding. Our results revealed two adjacent ligand-able
      pockets of HDAC6 Zf-UBD and the first functional ligands for this domain.

PMID- 29019678
TI  - Total Synthesis and Biological Mode of Action of WAP-8294A2: A Menaquinone
      Targeting Antibiotic.
AB  - WAP-8294A2 (lotilibcin, 1) is a potent antibiotic with superior in vivo efficacy
      to vancomycin against methicillin-resistant Staphylococcus aureus (MRSA). Despite
      the great medical importance, its molecular mode of action remains unknown. Here
      we report the total synthesis of complex macrocyclic peptide 1 comprised of 12
      amino acids with a beta-hydroxy fatty-acid chain, and its deoxy analogue 2. A
      full solid-phase synthesis of 1 and 2 enabled their rapid assembly and the first
      detailed investigation of their functions. Compounds 1 and 2 were equipotent
      against various strains of Gram-positive bacteria including MRSA. We present
      evidence that the antimicrobial activities of 1 and 2 are due to lysis of the
      bacterial membrane, and their membrane-disrupting effects depend on the presence
      of menaquinone, an essential factor for the bacterial respiratory chain. The
      established synthetic routes and the menaquinone-targeting mechanisms provide
      valuable information for designing and developing new antibiotics based on their
      structures.

PMID- 29019677
TI  - Scalaradial Is a Potent Inhibitor of Transient Receptor Potential Melastatin 2
      (TRPM2) Ion Channels.
AB  - TRPM2 is a Ca2+-permeable, nonselective cation channel that plays a role in
      oxidant-induced cell death, insulin secretion, and cytokine release. Few TRPM2
      inhibitors have been reported, which hampers the validation of TRPM2 as a drug
      target. While screening our in-house marine-derived chemical library, we
      identified scalaradial and 12-deacetylscalaradial as the active components within
      an extract of an undescribed species of Cacospongia (class Demospongiae, family
      Thorectidae) that strongly inhibited TRPM2-mediated Ca2+ influx in TRPM2
      overexpressing HEK293 cells. In whole-cell patch-clamp experiments, scalaradial
      (and similarly 12-deacetylscalaradial) inhibited TRPM2-mediated currents in a
      concentration- and time-dependent manner (~20 min to full onset; IC50 210 nM).
      Scalaradial inhibited TRPM7 with less potency (IC50 760 nM) but failed to inhibit
      CRAC, TRPM4, and TRPV1 currents in whole-cell patch clamp experiments.
      Scalaradial's effect on TRPM2 channels was shown to be independent of its well
      known ability to inhibit secreted phospholipase A2 (sPLA2) and its reported
      effects on extracellular signal-regulated kinases (ERK) and Akt pathways. In
      addition, scalaradial was shown to inhibit endogenous TRPM2 currents in a rat
      insulinoma cell line (IC50 330 nM). Based on its potency and emerging specificity
      profile, scalaradial is an important addition to the small number of known TRPM2
      inhibitors.

PMID- 29019679
TI  - Quantum Chemistry in Dataflow: Density-Fitting MP2.
AB  - We demonstrate the use of dataflow technology in the computation of the
      correlation energy in molecules at the Moller-Plesset perturbation theory (MP2)
      level. Specifically, we benchmark density fitting (DF)-MP2 for as many as 168
      atoms (in valinomycin) and show that speed-ups between 3 and 3.8 times can be
      achieved when compared to the MOLPRO package run on a single CPU. Acceleration is
      achieved by offloading the matrix multiplications steps in DF-MP2 to Dataflow
      Engines (DFEs). We project that the acceleration factor could be as much as 24
      with the next generation of DFEs.

PMID- 29019680
TI  - Elucidating the Limiting Steps in Sulfuric Acid-Base New Particle Formation.
AB  - The molecular interactions between sulfuric acid (sa) and methylamine (ma) are
      investigated using computational methods. The molecular structures and
      vibrational frequencies of (sa)a(ma)b clusters, with a, b <= 4, were obtained
      with the omegaB97X-D functional using a 6-31++G(d,p) basis set. The single-point
      energies were corrected using the domain-based local pair natural orbital coupled
      cluster method-DLPNO-CCSD(T)-with an aug-cc-pVTZ basis set. The calculated Gibbs
      free energies (DeltaG) of the clusters are used to calculate the evaporation
      rates of the (sa)a(ma)b cluster system and compare them to the corresponding
      ammonia clusters. With the atmospheric cluster dynamics code (ACDC), the new
      particle formation rates of the (sa)a(ma)b clusters were simulated and compared
      to the (sa)a(dma)b cluster system. It is found that methylamine is not capable of
      explaining observed new particle formation event in the ambient atmosphere.
      Looking into the calculated Gibbs free energy profiles it is found that the
      limiting steps in forming stable (sa)3-4(base)3-4 clusters depend strongly on the
      formation of the (sa)1(base)1 and (sa)2(base)2 clusters. These findings further
      support that compounds with high basicity are required to form the very initial
      cluster nucleus, which serves as the basis for forming new particles in the
      atmosphere.

PMID- 29019681
TI  - Cyclobutyl-Containing Rigid Analogues of Threonine: Synthesis and Physical
      Chemical Properties.
AB  - Hitherto unknown cis- and trans-1-amino-3-hydroxy-3-methylcyclobutanecarboxylic
      acids were synthesized in multigram scale. The obtained compounds can be
      considered as achiral conformationally restricted analogues of threonine with
      fixed spatial orientation of functional groups. pKa values are noticeably
      different for both amino acids. According to the X-ray data the cyclobutane rings
      in both compounds are almost planar (the corresponding torsion angles are below 7
      degrees ).

PMID- 29019682
TI  - Synthesis of beta-Ketosulfonamides Derived from Amino Acids and Their Conversion
      to beta-Keto-alpha,alpha-difluorosulfonamides via Electrophilic Fluorination.
AB  - beta-Ketosulfonamides derived from Boc or Cbz-protected amino acids bearing
      hydrophobic side chains were prepared in good to excellent yield by treating N
      allyl, N-alkyl methanesulfonamides with n-BuLi, followed by reaction of the
      resulting carbanion with methyl esters of N-protected l-amino acids. The
      analogous reaction using the dianion derived from an N-alkyl methanesulfonamide
      proceeded in much lower yield. Electrophilic fluorination of the beta
      ketosulfonamides using Selectfluor in the presence of CsF in DMF at room
      temperature for 15-60 min provided beta-keto-alpha,alpha-difluorosulfonamides in
      good to excellent yields. The allyl protecting group could be removed in good
      yield using cat. Pd(PPh)3)4 and dimethyl barbituric acid. When the fluorination
      reaction was performed with Cs2CO3 as base, beta-ketosulfonamides derived from
      Val, Leu or Ile gave the expected beta-keto-alpha,alpha-difluorosulfonamides,
      while beta-ketosulfonamides derived from Ala, Phe, or hPhe gave the hydrates of
      the imino beta-keto-alpha,alpha-difluorosulfonamides.

PMID- 29019683
TI  - Self-Assembly Pathways of beta-Sheet-Rich Amyloid-beta(1-40) Dimers: Markov State
      Model Analysis on Millisecond Hybrid-Resolution Simulations.
AB  - Early oligomerization during amyloid-beta (Abeta) aggregation is essential for
      Abeta neurotoxicity. Understanding how unstructured Abetas assemble into
      oligomers, especially those rich in beta-sheets, is essential but remains
      challenging as the assembly process is too transient for experimental
      characterization and too slow for molecular dynamics simulations. So far, atomic
      simulations are limited only to studies of either oligomer structures or assembly
      pathways for short Abeta segments. To overcome the computational challenge, we
      combine in this study a hybrid-resolution model and adaptive sampling techniques
      to perform over 2.7 ms of simulations of formation of full-length Abeta40 dimers
      that are the earliest toxic oligomeric species. The Markov state model is further
      employed to characterize the transition pathways and associated kinetics. Our
      results show that for two major forms of beta-sheet-rich structures reported
      experimentally, the corresponding assembly mechanisms are markedly different.
      Hairpin-containing structures are formed by direct binding of soluble Abeta in
      beta-hairpin-like conformations. Formation of parallel, in-register structures
      resembling fibrils occurs ~100-fold more slowly and involves a rapid encounter of
      Abeta in arbitrary conformations followed by a slow structural conversion. The
      structural conversion proceeds via diverse pathways but always requires transient
      unfolding of encounter complexes. We find that the transition kinetics could be
      affected differently by intra-/intermolecular interactions involving individual
      residues in a conformation-dependent manner. In particular, the interactions
      involving Abeta's N-terminal part promote the assembly into hairpin-containing
      structures but delay the formation of fibril-like structures, thus explaining
      puzzling observations reported previously regarding the roles of this region in
      the early assembly process.

PMID- 29019684
TI  - Serinolamides and Lyngbyabellins from an Okeania sp. Cyanobacterium Collected
      from the Red Sea.
AB  - NMR- and MS-guided fractionation of an extract of an Okeania sp. marine
      cyanobacterium, collected from the Red Sea, led to the isolation of four new
      metabolites, including serinolamides C (1) and D (2) and lyngbyabellins O (3) and
      P (4), together with the three known substances lyngbyabellins F (5) and G (6)
      and dolastatin 16 (7). The planar structures of the new compounds were determined
      using NMR and MS analyses. The absolute configurations of 1 and 2 were determined
      by Marfey's analysis of their hydrolysates. The absolute configuration of 3 was
      ascertained by chiral-phase chromatography of degradation products, while that of
      4 was determined by comparison to 3 and 5. The cytotoxic and antifouling
      activities of these compounds were evaluated using MCF7 breast cancer cells and
      Amphibalanus amphitrite larvae, respectively. Compounds 3, 4, and 7 exhibited
      strong antifouling activity, and 3 and 7 were not cytotoxic. A structure-activity
      relationship was observed for the cytotoxicity of the lyngbyabellins with the
      presence of a side chain (4 is more active than 3) leading to greater activity.
      For the antifouling activity, the acyclic form without a side chain (3) was the
      most active.

PMID- 29019685
TI  - Structures and Antibacterial Properties of Isorugosins H-J, Oligomeric
      Ellagitannins from Liquidambar formosana with Characteristic Bridging Groups
      between Sugar Moieties.
AB  - Three new ellagitannin oligomers, isorugosins H (1), I (2), and J (3), together
      with 11 known hydrolyzable tannins were isolated from an aqueous acetone extract
      of the fresh leaves of Liquidambar formosana. Their chemical structures were
      elucidated based on spectroscopic data and chemical conversion into known
      hydrolyzable tannins. The bridging mode of the valoneoyl groups between their
      sugar moieties has been identified only in this plant species. Additionally, the
      effects of the isorugosins isolated from this species on drug-resistant bacteria
      were evaluated and showed that isorugosin A (4) exhibited the most potent
      antibacterial activity against methicillin-resistant Staphylococcus aureus
      (MRSA). The isorugosins also had a suppressing effect on pigment formation in
      Pseudomonas aeruginosa. The isorugosin-protein complexes were analyzed using size
      exclusion chromatography and polyacrylamide gel electrophoresis to clarify the
      relationship of their antibacterial properties with their protein interaction
      potency as hydrolyzable tannins. The results suggested that the antibacterial
      properties of hydrolyzable tannins are not simply a result of their binding
      activity to proteins, but are due to other factors such as the accessibility of
      polyphenolic acyl groups to bacterial membranes.

PMID- 29019686
TI  - Virtual Exploration of the Ring Systems Chemical Universe.
AB  - Here, we explore the chemical space of all virtually possible organic molecules
      focusing on ring systems, which represent the cyclic cores of organic molecules
      obtained by removing all acyclic bonds and converting all remaining atoms to
      carbon. This approach circumvents the combinatorial explosion encountered when
      enumerating the molecules themselves. We report the chemical universe database
      GDB4c containing 916 130 ring systems up to four saturated or aromatic rings and
      maximum ring size of 14 atoms and GDB4c3D containing the corresponding 6 555 929
      stereoisomers. Almost all (98.6%) of these ring systems are unknown and represent
      chiral 3D-shaped macrocycles containing small rings and quaternary centers
      reminiscent of polycyclic natural products. We envision that GDB4c can serve to
      select new ring systems from which to design analogs of such natural products.
      The database is available for download at www.gdb.unibe.ch together with
      interactive visualization and search tools as a resource for molecular design.

PMID- 29019687
TI  - Simulated Dynamics of Glycans on Ligand-Binding Domain of NMDA Receptors Reveals
      Strong Dynamic Coupling between Glycans and Protein Core.
AB  - N-Methyl-d-aspartate (NMDA) receptors, key neuronal receptors playing the central
      role in learning and memory, are heavily glycosylated in vivo. Astonishingly
      little is known about the structure, dynamics, and physiological relevance of
      glycans attached to them. We recently demonstrated that certain glycans on the
      ligand binding domain (LBD) of NMDA receptors (NMDARs) can serve as
      intramolecular potentiators, changing EC50 of NMDAR coagonists. In this work, we
      use molecular dynamics trajectories, in aggregate 86.5 MUs long, of the
      glycosylated LBD of the GluN1 subunit of the NMDAR to investigate the behavior of
      glycans on NMDARs. Though all glycans in our simulations were structurally the
      same (Man5), the dynamics of glycans at different locations on NMDARs was
      surprisingly different. The slowest-time scale motions that we detected in
      various glycans in some cases corresponded to a flipping of parts of glycans
      relative to each other, while in other cases they reduced to a head-to-tail
      bending of a glycan. We predict that time scales of conformational changes in
      glycans on the GluN1 LBD of NMDARs range from nanoseconds to at least hundreds of
      microseconds. Some of the conformational changes in the glycans correlate with
      the physiologically important clamshell-like opening and closing of the GluN1 LBD
      domain. Thus, glycans are an integral part of NMDARs, and computational models of
      NMDARs should include glycans to faithfully represent the structure and the
      dynamics of these receptors.

PMID- 29019688
TI  - Yb(OTf)3-Catalyzed Desymmetrization of myo-Inositol 1,3,5-Orthoformate and Its
      Application in the Synthesis of Chiral Inositol Phosphates.
AB  - A variety of inositol phosphates including myo-inositol 1,4,5-trisphosphate,
      which is a secondary messenger in transmembrane signaling, were selectively
      synthesized via Yb(OTf)3-catalyzed desymmetrization of myo-inositol 1,3,5
      orthoformate using a proline-based chiral anhydride as an acylation precursor.
      The investigated catalytic system could regioselectively differentiate the
      enantiotopic hydroxy groups of myo-inositol 1,3,5-orthoformate in the presence of
      a chiral auxiliary. This key step to generate a suitably protected chiral myo
      inositol derivatives is described here as a unified approach to access inositol
      phosphates.

PMID- 29019689
TI  - Improving the Efficiency of Beyond-RPA Methods within the Dielectric Matrix
      Formulation: Algorithms and Applications to the A24 and S22 Test Sets.
AB  - Within a formalism based on dielectric matrices, the electron-hole time-dependent
      Hartree-Fock (eh-TDHF) and the adiabatic connection second-order screened
      exchange (AC-SOSEX) are promising approximations to improve ground-state
      correlation energies by including exchange effects beyond the random phase
      approximation (RPA). We introduce here an algorithm based on a Gram-Schmidt
      orthogonalization (GSO) procedure that significantly reduce the number of matrix
      elements to be computed to evaluate the response functions that enter in the
      formulation of these two methods. By considering the A24 test set, we show that
      this approach does not lead to a significant loss of accuracy and can be
      effectively applied to compute the small interaction energies involved in weakly
      bound dimers. Importantly, the GSO method significantly extends the applicability
      of the eh-TDHF and AC-SOSEX to large systems. This is shown by considering the
      S22 test set, which includes dimers with up to one hundred valence electrons
      requiring hundreds of thousands of plane-waves in the basis set. By comparing our
      results to coupled-cluster benchmark values, we show that the inclusion of
      exchange effects beyond the RPA significantly improves the accuracy, with mean
      absolute errors that decrease by almost 40% for the A24 test set and by almost
      50% for the S22 test set. This approach based on dielectric matrices is
      particularly suited for plane-wave implementations and might be used in the
      future to improve the description of the correlation energy in solid state
      applications.

PMID- 29019691
TI  - pH-Induced Changes in the Surface Viscosity of Unsaturated Phospholipids
      Monitored Using Active Interfacial Microrheology.
AB  - Lipid membranes, a major component of cells, are subjected to significant changes
      in pH depending on their location in the cell: the outer leaflet of the cell
      membrane is exposed to a pH of 7.4 whereas lipid membranes that make up late
      endosomes and lysosomes are exposed to a pH of as low as 4.4. The purpose of this
      study is to evaluate how changes in the environmental pH within cells alter the
      fluidity of phospholipid membranes. Specifically, we studied pH-induced
      alterations in the surface arrangement of monounsaturated lipids with
      zwitterionic headgroups (phosphoethanolamine (PE) and phosphocholine (PC)) that
      are abundant in plasma membranes as well as anionic lipids (phosphatidylserine
      (PS) and phosphatidylglycerol (PG)) that are abundant in inner membranes using a
      combination of techniques including surface tension vs area measurements,
      interfacial microrheology, and fluorescence/atomic force microscopy. Using an
      active interfacial microrheology technique, we find that phospholipids with
      zwitterionic headgroups show a significant increase in their surface viscosity at
      acidic pH. This increase in surface viscosity is also found to depend on the size
      of the lipid headgroup, with a smaller headgroup showing a greater increase in
      viscosity. The observed pH-induced increase in viscosity is also accompanied by
      an increase in the cohesion pressure between zwitterionic molecules at acidic pH
      and a decrease in the average molecular area of the lipids, as measured by
      fitting the surface pressure isotherms to well-established equations of state.
      Because fluorescent images show no change in the phase of the lipids, we
      attribute this change in surface viscosity to the pH-induced reorientation of the
      P--N+ dipoles that form part of the polar lipid headgroup, resulting in increased
      lipid-lipid interactions. Anionic PG headgroups do not demonstrate this pH
      induced change in viscosity, suggesting that the presence of a net negative
      charge on the headgroup causes electrostatic repulsion between the headgroups.
      Our results also show that active interfacial microrheology is a sensitive
      technique for detecting minute changes in the lipid headgroup orientation induced
      by changes in the local membrane environment, even in unsaturated phospholipids
      where the surface viscosity is close to the experimental detection limit.

PMID- 29019692
TI  - Tuning the Electrocatalytic Oxygen Reduction Reaction Activity and Stability of
      Shape-Controlled Pt-Ni Nanoparticles by Thermal Annealing - Elucidating the
      Surface Atomic Structural and Compositional Changes.
AB  - Shape-controlled octahedral Pt-Ni alloy nanoparticles exhibit remarkably high
      activities for the electroreduction of molecular oxygen (oxygen reduction
      reaction, ORR), which makes them fuel-cell cathode catalysts with exceptional
      potential. To unfold their full and optimized catalytic activity and stability,
      however, the nano-octahedra require post-synthesis thermal treatments, which
      alter the surface atomic structure and composition of the crystal facets. Here,
      we address and strive to elucidate the underlying surface chemical processes
      using a combination of ex situ analytical techniques with in situ transmission
      electron microscopy (TEM), in situ X-ray diffraction (XRD), and in situ
      electrochemical Fourier transformed infrared (FTIR) experiments. We present a
      robust fundamental correlation between annealing temperature and catalytic
      activity, where a ~25 times higher ORR activity than for commercial Pt/C (2.7 A
      mgPt-1 at 0.9 VRHE) was reproducibly observed upon annealing at 300  degrees C.
      The electrochemical stability, however, peaked out at the most severe heat
      treatments at 500  degrees C. Aberration-corrected scanning transmission electron
      microscopy and energy-dispersive X-ray spectroscopy (EDX) in combination with in
      situ electrochemical CO stripping/FTIR data revealed subtle, but important,
      differences in the formation and chemical nature of Pt-rich and Ni-rich surface
      domains in the octahedral (111) facets. Estimating trends in surface
      chemisorption energies from in situ electrochemical CO/FTIR investigations
      suggested that balanced annealing generates an optimal degree of Pt surface
      enrichment, while the others exhibited mostly Ni-rich facets. The insights from
      our study are quite generally valid and aid in developing suitable post-synthesis
      thermal treatments for other alloy nanocatalysts as well.

PMID- 29019693
TI  - Dynamic Structuration of Physical Chitosan Hydrogels.
AB  - We studied the microstructure of physical chitosan hydrogels formed by the
      neutralization of chitosan aqueous solutions highlighting the structural
      gradients within thick gels (up to a thickness of 16 mm). We explored a high
      polymer concentrations range (Cp >= 1.0% w/w) with different molar masses of
      chitosan and different concentrations of the coagulation agent. The effect of
      these processing parameters on the morphology was evaluated mainly through small
      angle light scattering (SALS) measurements and confocal laser scanning microscopy
      (CLSM) observations. As a result, we reported that the microstructure is
      continuously evolving from the surface to the bulk, with mainly two structural
      transitions zones separating three types of hydrogels. The first zone (zone I) is
      located close to the surface of the hydrogel and constitutes a hard (entangled)
      layer formed under fast neutralization conditions. It is followed by a second
      zone (zone II) with a larger thickness (~3-4 mm), where in some cases large pores
      or capillaries (diameter ~10 MUm) oriented parallel to the direction of the gel
      front are present. Deeper in the hydrogel (zone III), a finer oriented
      microstructure, with characteristic sizes lower than 2-3 MUm, gradually replace
      the capillary morphology. However, this last bulk morphology cannot be regarded
      as structurally uniform because the size of small micrometer-range-oriented pores
      continuously increases as the distance to the surface of the hydrogel increases.
      These results could be rationalized through the effect of coagulation kinetics
      impacting the morphology obtained during neutralization.

PMID- 29019695
TI  - Total Synthesis of Biselide E, a Marine Polyketide.
AB  - The total synthesis of biselide E, a marine polyketide isolated from the Okinawan
      ascidian, has been accomplished. The highlight of this approach is the use of the
      beta-elimination reaction of the chloroacetoxy group for the construction of an
      unstable six-membered alpha,beta,gamma,delta-unsaturated lactone portion at the
      late stage of the total synthesis.

PMID- 29019694
TI  - Zwitterionic and Charged Lipids Form Remarkably Different Structures on Nanoscale
      Oil Droplets in Aqueous Solution.
AB  - The molecular structure of zwitterionic and charged monolayers on small oil
      droplets in aqueous solutions is determined using a combined second harmonic and
      sum frequency study. From the interfacial vibrational signature of the acyl
      chains and phosphate headgroups as well as the response of the hydrating water,
      we find that zwitterionic and charged lipids with identical acyl chains form
      remarkably different monolayers. Zwitterionic phospholipids form a closely packed
      monolayer with highly ordered acyl tails. In contrast, the charged phospholipids
      form a monolayer with a low number density and disordered acyl tails. The charged
      headgroups are oriented perpendicular to the monolayer rather than parallel, as
      is the case for zwitterionic lipids. These significant differences between the
      two types of phospholipids indicate important roles of phospholipid headgroups in
      the determination of properties of cellular membranes and lipid droplets. The
      observed behavior of charged phospholipids is different from expectations based
      on studies performed on extended planar interfaces, at which condensed monolayers
      are readily formed. The difference can be explained by nanoscale related changes
      in charge condensation behavior that has its origin in a different balance of
      interfacial intermolecular interactions.

PMID- 29019696
TI  - Metal Substitution in Keggin-Type Tridecameric Aluminum-Oxo-Hydroxy Clusters.
AB  - The species resulting from a typical preparation for metal-substituted hybrids of
      the Keggin tridecamer, Al13 or [AlO4Al12(OH)24(OH2)12]7+, were examined by
      performing 27Al NMR on the solutions during aging and by studying the
      precipitated sulfate salts via solid state 27Al NMR and powder X-ray diffraction
      (XRD). Aqueous mixtures (0.25 mol L-1) of AlCl3 and another metal ion (M), in a
      12:1 mole ratio (Al:M), where M = Fe3+, Zn2+, Ga3+, In3+, Sn2+, La3+, and Bi3+,
      were subjected to forced hydrolysis by addition of NaOH (1.0 mol L-1) until
      OH/(Al + M) = 2.25, and the kinetics of Al13 formation and disappearance with
      aging at 80  degrees C was monitored by 27Al NMR spectroscopy. Al13 units
      polymerize on aging with an apparent rate constant (k) of 4.8(8) * 10-2 h-1 to
      form a species referred to as AlP2. Only the solutions containing Ga3+ and Sn2+
      exhibited faster Al13 conversion rates. GaAl12 forms quickly at 80  degrees C (k
      = 0.54 h-1) and is more stable than AlP2. Sn2+ apparently promotes AlP2 formation
      (k = 0.38 h-1). XRD and solid state NMR reveal that only the Ga hybrid can be
      prepared by this method. No hybrid formation was evidenced using M = Mg2+, Fe3+,
      Co2+, Ni2+, Cu2+, Zn2+, In3+, La3+, or Ce3+ at 25  degrees C or M = Co2+ or La3+
      under reflux conditions. Isostructural (cubic symmetry) single crystals were
      obtained for the sulfate salts of Al13 and GaAl12. Single-crystal XRD analysis of
      these two polyoxocations provides the first rigorous comparison between them and
      shows they have very similar structures. The main crystallographic data for Al13
      and GaAl12 are as follows:  Na[AlO4Al12(OH)24(H2O)12](SO4)4.10H2O, cubic, F43m, a
      = 17.856(2) A, Z = 4; Na[GaO4Al12(OH)24(H2O)12](SO4)4.10H2O, cubic, F43m, a =
      17.869(3) A, Z = 4. Thus, the greater thermal stability of GaAl12 cannot be
      rationalized in terms of the overall geometric considerations, as suggested by
      others. Solid state NMR also shows the coordination symmetries of the outer 12 Al
      nuclei in both clusters to be similar.

PMID- 29019698
TI  - Palivizumab Prophylaxis and Recurrent Wheezing.

PMID- 29019699
TI  - Reply to Kovesi, to Chabra, and to Farber: "Palivizumab Prophylaxis and Recurrent
      Wheezing" and "Precise Gestational Age Definitions Needed for Palivizumab
      Prophylaxis in Preterm Infants" and "Imbalance in Level of Tobacco Smoke Exposure
      Between Groups Likely Explains the "Effect" of Palivizumab on Subsequent
      Wheezing".

PMID- 29019697
TI  - Development of Potent Type I Protein Arginine Methyltransferase (PRMT) Inhibitors
      of Leukemia Cell Proliferation.
AB  - Protein Arginine Methyltransferases (PRMTs) are crucial players in diverse
      biological processes, and dysregulation of PRMTs has been linked to various human
      diseases, especially cancer. Therefore, small molecules targeting PRMTs have
      profound impact for both academic functional studies and clinical disease
      treatment. Here, we report the discovery of N1-(2-((2-chlorophenyl)thio)benzyl)
      N1-methylethane-1,2-diamine (28d, DCPR049_12), a highly potent inhibitor of type
      I PRMTs that has good selectivity against a panel of other methyltransferases.
      Compound 28d effectively inhibits cell proliferation in several leukemia cell
      lines and reduces the cellular asymmetric arginine dimethylation levels. Serving
      as an effective inhibitor, 28d demonstrates the mechanism of cell killing in both
      cell cycle arrest and apoptotic effect as well as downregulation of the pivotal
      mixed lineage leukemia (MLL) fusion target genes such as HOXA9 and MEIS1, which
      reflects the critical roles of type I PRMTs in MLL leukemia. These studies
      present 28d as a valuable inhibitor to investigate the role of type I PRMTs in
      cancer and other diseases.

PMID- 29019701
TI  - Precise Gestational Age Definitions Needed for Palivizumab Prophylaxis in Preterm
      Infants.

PMID- 29019700
TI  - Taillessness in a Cloned Cow is Not Genetically Transmitted.
AB  - Somatic cell nuclear transfer (SCNT), commonly referred to as cloning, results in
      the generation of offspring that, except for mitochondrial DNA, are genetically
      identical to the nuclear donor. We previously used a genetically modified bovine
      cell line as the donor for SCNT and obtained a calf, named Daisy, that was born
      without a tail. To determine whether the missing tail was a result of the genetic
      modification, we performed recloning experiments by using either cells from a
      sacrificed pregnancy of a second clone (Daisy's "twin" clone) or cells from
      tailless Daisy as donors for SCNT. Cloned fetuses from aborted pregnancies and a
      cloned live calf that died shortly after birth were examined and confirmed to all
      possess tails. Hence, the observed phenotype of Daisy's lacking tail is not due
      to the introduced transgene or a mutation present in the cell that was used for
      her production. Rather, the missing tail has most likely arisen from an
      epigenetic reprogramming error during development.

PMID- 29019703
TI  - Imbalance in Level of Tobacco Smoke Exposure Between Groups Likely Explains the
      "Effect" of Palivizumab on Subsequent Wheezing.

PMID- 29019702
TI  - Inhibition of Phosphoglycerate Dehydrogenase Attenuates Bleomycin-induced
      Pulmonary Fibrosis.
AB  - Organ fibrosis, including idiopathic pulmonary fibrosis, is associated with
      significant morbidity and mortality. Because currently available therapies have
      limited effect, there is a need to better understand the mechanisms by which
      organ fibrosis occurs. We have recently reported that transforming growth factor
      (TGF)-beta, a key cytokine that promotes fibrogenesis, induces the expression of
      the enzymes of the de novo serine and glycine synthesis pathway in human lung
      fibroblasts, and that phosphoglycerate dehydrogenase (PHGDH; the first and rate
      limiting enzyme of the pathway) is required to promote collagen protein synthesis
      downstream of TGF-beta. In this study, we investigated whether inhibition of de
      novo serine and glycine synthesis attenuates lung fibrosis in vivo. We found that
      TGF-beta induces mRNA and protein expression of PHGDH in murine fibroblasts.
      Similarly, intratracheal administration of bleomycin resulted in increased
      expression of PHGDH in mouse lungs, localized to fibrotic regions. Using a newly
      developed small molecule inhibitor of PHGDH (NCT-503), we tested whether
      pharmacologic inhibition of PHGDH could inhibit fibrogenesis both in vitro and in
      vivo. Treatment of murine and human lung fibroblasts with NCT-503 decreased TGF
      beta-induced collagen protein synthesis. Mice treated with the PHGDH inhibitor
      beginning 7 days after intratracheal instillation of bleomycin had attenuation of
      lung fibrosis. These results indicate that the de novo serine and glycine
      synthesis pathway is necessary for TGF-beta-induced collagen synthesis and
      bleomycin-induced pulmonary fibrosis. PHGDH and other enzymes in the de novo
      serine and glycine synthesis pathway may be a therapeutic target for treatment of
      fibrotic diseases, including idiopathic pulmonary fibrosis.

PMID- 29019704
TI  - Fair Is Fair: Just Visiting Hours and Reducing Inequities.
AB  - Although family is an essential unit of every society, many intensive care units
      continue to impose limitations on families' access to their loved ones. Unlimited
      family presence is backed both by data and the guidelines of multiple
      professional societies. We propose that the obligation to protect the integrity
      and needs of our patients and families extends past our immediate relationship to
      them at the bedside, and is also a societal imperative. In a society rife with
      implicit bias, restrictions on family visitation risk selective enforcement of
      these rules, and further propagate social injustice. Restrictions on family
      presence, including rigid hours, reflect an arbitrary vision based on
      increasingly obsolete socioeconomic realities. The time is now to open our
      intensive care units both on behalf of our patients and families, and for the
      betterment of our society as a whole.

PMID- 29019705
TI  - Validation of a Difficulty Grading Score in Laparoscopic Splenectomy.
AB  - INTRODUCTION: Laparoscopic splenectomy (LS) is the gold standard for the
      treatment of many spleen-related disorders. However, in the presence of
      splenomegaly, the rate of conversion to open surgery can be as high as 33.9% and
      is associated with longer operative times and higher costs. In an attempt to
      improve risk stratification and patient selection for LS, a score that includes
      four preoperative parameters (age, gender, diagnosis, and spleen size) has been
      developed. The aim was the validation of a difficulty grading score, in
      predicting conversion and poorer outcomes. METHODS: Retrospective analysis of 153
      consecutive patients subjected to LS from January 2006 through December 2016 was
      performed. Several parameters were reviewed and correlation with evaluated
      outcomes was analyzed. RESULTS: Conversion to open surgery occurred in 13 (8.50%)
      patients and was highly associated with serious intraoperative complications.
      Spearman correlation showed a significant association between the score and risk
      of conversion, operative time, and postoperative complications, but not with
      intraoperative bleeding. DISCUSSION: Patient and disease features, incorporated
      in a difficulty grading score, can reliably determine the difficulty of LS and
      predict risk of conversion, intraoperative, and postoperative complications. This
      simple and reproducible score improves risk stratification for LS and could be
      practical in daily clinical activities.

PMID- 29019706
TI  - Institutional Scientific Review of Cancer Clinical Research Protocols: A Unique
      Requirement That Affects Activation Timelines.
AB  - PURPOSE: The National Cancer Institute (NCI) requirement that clinical trials at
      NCI-designated cancer centers undergo institutional scientific review in addition
      to institutional review board evaluation is unique among medical specialties. We
      sought to evaluate the effect of this process on protocol activation timelines.
      METHODS: We analyzed oncology clinical trials that underwent full board review by
      the Harold C. Simmons Comprehensive Cancer Center Protocol Review and Monitoring
      Committee (PRMC) from January 1, 2009, through June 30, 2013. We analyzed
      associations between trial characteristics, PRMC decisions, protocol
      modifications, and process timelines using the chi2 test, Fisher's exact test,
      Wilcoxon rank sum test, Kruskal-Wallis test, and logistic regression. RESULTS: A
      total of 226 trials were analyzed. Of these, 77% were industry sponsored and 23%
      were investigator initiated. The median time from submission to PRMC approval was
      55 days. The length of review was associated with trial phase, timing of
      approval, and number of committee changes/clarifications requested. The median
      process time was 35 days for those approved at first decision, 68 days for second
      decision, and 116 days for third decision ( P < .001). The median process time
      was 39 days if no changes/clarifications were requested, 64 days for one to three
      changes/clarifications, and 73 days for four or more changes/clarifications ( P <
      .001). Requested changes/clarifications had a greater effect on industry
      sponsored trials than on investigator-initiated trials. CONCLUSION: NCI-mandated
      institutional scientific review of oncology clinical trials contributes
      substantially to protocol activation timelines. Further evaluation of this
      process and the value added to research quality is warranted.

PMID- 29019708
TI  - Effects of long-term exercise and low-level inhibition of GABAergic synapses on
      motor control and the expression of BDNF in the motor related cortex.
AB  - Objectives Brain-derived neurotrophic factor (BDNF) plays important roles in
      neuroplasticity in the brain. The objective of this study was to examine the
      effects of long-term exercise combined with low-level inhibition of GABAergic
      synapses on motor control and the expression of BDNF in the motor-related cortex.
      Methods ICR mice were divided into four groups based on the factors exercise and
      GABAA receptor inhibition. We administered the GABAA receptor antagonist
      bicuculline intraperitoneally (0.25 mg/kg). Mice exercised on a treadmill 5
      days/week for 4 weeks. Following behavioral tests, BDNF expression in the motor
      cortex and cerebellar cortex was assayed using RT-PCR and ELISA. Results Exercise
      increased BDNF protein in the motor cortex and improved motor coordination in the
      rotarod test either in the presence or absence of bicuculline. BDNF mRNA
      expression in the motor cortex and muscle coordination in the wire hang test
      decreased after administration of bicuculline, whereas bicuculline administration
      increased mRNA and protein expression of BDNF in the cerebellum. Discussion The
      present study revealed that long-term exercise increased BDNF expression in the
      motor cortex and facilitated a transfer of motor learning from aerobic exercise
      to postural coordination. Thus, aerobic exercise is meaningful for conditioning
      motor learning to rehabilitate patients with central nervous system (CNS)
      disorders. However, long-term inhibition of GABAA receptors decreased the
      expression of cortical BDNF mRNA and decreased muscle coordination, despite the
      increase of BDNF in the cerebellum, suggesting that we have to consider the term
      of the inhibition of the GABAergic receptor for future clinical application to
      CNS patients.

PMID- 29019709
TI  - Laparoscopic Varicocelectomy Using Polymeric Ligating Clips and Its Effect on
      Semen Parameters in Pediatric Population with Symptomatic Varicocele: A 5-Year
      Single Surgeon Experience.
AB  - BACKGROUND: The aim of this study was to evaluate demographic and clinical
      characteristics of the children undergoing laparoscopic varicocelectomy by using
      polymeric ligating clips and to evaluate postoperative outcomes and analyze semen
      according to the grade of varicocele after surgery. PATIENTS AND METHODS: The
      case records of 120 pediatric patients who underwent laparoscopic varicocelectomy
      were retrospectively reviewed. The following parameters were examined: age, grade
      of varicocele, lateralization, diameter of spermatic veins, indications for
      surgery, duration and outcomes of surgery, complications, and recurrence rate.
      For patients older than 16 years of age, semen analyses were obtained before and
      after the surgery and were compared according to the clinical grade of
      varicocele. RESULTS: The median age of the patients was 15 years. Of the total
      number of patients, left-sided varicocele was found in 119 patients and bilateral
      varicocele was found in 1 patient. Of the 120 varicoceles, 8 (6.7%) were grade I,
      58 (48.3%) were grade II, and 54 (45%) were grade III. There were no major
      intraoperative complications. Hydrocele was found in 2 (1.6%) patients. There
      were no cases of recurrence recorded. Sperm concentration (P < .01), morphology
      (P < .01), and motility (P < .01; P = .02) improved 6 months after surgery in
      patients with varicocele grades of I and II, respectively. In grade III
      varicocele, only sperm concentration (P < .01) and morphology (P = .03) improved
      whereas motility (P = .150) did not change significantly. CONCLUSION:
      Laparoscopic varicocelectomy using polymeric ligating clips is a safe, feasible,
      and cost-effective technique, with a low rate of postoperative complications and
      recurrence and it significantly improves sperm parameters in adolescents.

PMID- 29019710
TI  - The View from Puerto Rico - Hurricane Maria and Its Aftermath.

PMID- 29019707
TI  - Glutaminolysis Promotes Collagen Translation and Stability via alpha
      Ketoglutarate-mediated mTOR Activation and Proline Hydroxylation.
AB  - Glutaminolysis is the metabolic process of glutamine, aberration of which has
      been implicated in several pathogeneses. Although we and others recently found a
      diversity of metabolic dysregulation in organ fibrosis, it is unknown if
      glutaminolysis regulates the profibrotic activities of myofibroblasts, the
      primary effector in this pathology. In this study, we found that lung
      myofibroblasts demonstrated significantly augmented glutaminolysis that was
      mediated by elevated glutaminase 1 (Gls1). Inhibition of glutaminolysis by
      specific Gls1 inhibitors CB-839 and BPTES as well as Gls1 siRNA blunted the
      expression of collagens but not that of fibronectin, elastin, or myofibroblastic
      marker smooth muscle actin-alpha. We found that glutaminolysis enhanced collagen
      translation and stability, which were mediated by glutaminolysis-dependent mTOR
      complex 1 activation and collagen proline hydroxylation, respectively.
      Furthermore, we found that the amount of the glutaminolytic end product alpha
      ketoglutarate (alpha-KG) was increased in myofibroblasts. Similar to
      glutaminolysis, alpha-KG activated mTOR complex 1 and promoted the expression of
      collagens but not of fibronectin, elastin, or smooth muscle actin-alpha. alpha-KG
      also remarkably inhibited collagen degradation in fibroblasts. Taken together,
      our studies identified a previously unrecognized mechanism by which a major
      metabolic program regulates the exuberant production of collagens in
      myofibroblasts and suggest that glutaminolysis is a novel therapeutic target for
      treating organ fibrosis, including idiopathic pulmonary fibrosis.

PMID- 29019711
TI  - Preparing for the Next Harvey, Irma, or Maria - Addressing Research Gaps.

PMID- 29019712
TI  - Creating Healthy Communities after Disasters.

PMID- 29019714
TI  - To the Editor.

PMID- 29019713
TI  - Modified Endoscopic Vacuum Therapy for Nonhealing Esophageal Anastomotic Leak:
      Technique Description and Review of Literature.
AB  - BACKGROUND: Endoscopic vacuum-assisted closure (EVAC) therapy is increasingly
      being used as a new promising method for repairing upper gastrointestinal defects
      of different etiologies with high success rates. EVAC therapy consists of placing
      a sponge either within the lumen or within an abscess cavity connected with a
      nasogastric (NG) tube to a negative pressure system, thus decreasing bacterial
      contamination and edema and promoting granulation tissue proliferation, thereby
      gradually decreasing the cavity size until complete closure. Herein, we describe
      a modified technique for EVAC therapy in which the NG tube is passed into the
      esophagus through an existing intrapleural drain tract using a rendezvous
      technique. The small residual fistula was amendable to fibrin glue embolization.
      This allows easier sponge placement and exchange compared to traditional EVAC
      technique, and allows oral intake during treatment. We also review the literature
      regarding other endoscopic treatment options for esophageal anastomotic leaks and
      perforations. METHODS: The PubMed database was searched using the terms
      "esophagus," "esophageal," "leak," "fistula," "endoluminal vacuum-assisted
      closure (VAC)," "endoscopic VAC," "stent," "sealant," "glue," and "over-the-scope
      clip (OTSC)." Reference lists of identified articles were searched for further
      articles, and the "similar articles" function was used on all included articles.
      RESULTS: Complete closure of the nonhealing fistula was achieved after 8 days of
      EVAC treatment and fibrin glue embolization. CONCLUSIONS: Modified EVAC technique
      as described is feasible and safe. To the best of our knowledge, this is the
      first description of this technique. The technique allows easier sponge placement
      and exchange compared to traditional EVAC technique, and allows oral intake
      during treatment.

PMID- 29019715
TI  - POSTOPERATIVE INSULIN REQUIREMENTS IN BARIATRIC SURGERY.
AB  - OBJECTIVE: Though insulin dose reduction months after surgery is a well-studied
      outcome, there are limited data on immediate postoperative changes. The goals of
      the present study were to ( 1) To determine peri-operative glycemic control in
      patients with type 2 diabetes mellitus (DM) on insulin who have undergone Roux-en
      Y gastric bypass (RYGB) and ( 2) to compare pre- and postoperative insulin
      regimens and dosages in these patients. METHODS: A retrospective chart review was
      conducted on patients with type 2 DM on insulin who underwent RYGB surgery. Blood
      glucose (BG) levels and insulin doses were compared prior to surgery, on the day
      of surgery (DOS), and postoperative days (POD) 1 and 2. Subgroup analysis was
      performed to see if insulin dose was related to glucose control. RESULTS: There
      were 114 subjects with a mean (SD) age of 52.8 +/- 9.8 years, body mass index
      (BMI) 46.2 +/- 8.0 kg/m2, glycated hemoglobin A1c (HbA1c) 8.3% (67 mmol/mol) +/-
      1.7%, and 66% on insulin plus noninsulin medications and 34% on insulin only.
      Mean blood glucose (BG) significantly decreased from the DOS (185 +/- 43 mg/dL)
      through POD2 (160 +/- 36, P<.0001). The median daily insulin dose significantly
      decreased from before surgery on usual diet (75 units [36, 116 interquartile
      range (IQR)]) through POD2 (6 [2, 15 IQR]), P<.0001). The median insulin dose per
      body weight decreased significantly from before surgery on usual diet (0.58
      units/kg [0.35, 0.84 IQR]) through POD2 (0.04 [0.02, 0.11 IQR]), P<.0001). The
      subgroup with relatively good control experienced a larger percentage reduction
      in insulin requirements versus subjects with poor control. CONCLUSION: An 87.5%
      reduction in total daily insulin dose was seen by POD2. This will assist in
      developing algorithms for insulin titration postbariatric surgery. ABBREVIATIONS:
      BG = blood glucose DM = diabetes mellitus DOS = day of surgery HbA1c = glycated
      hemoglobin IQR = interquartile range IV = intravenous NPH = neutral protamine
      Hagedorn POD = postoperative day RYGB = Roux-en-Y gastric bypass SSRI = sliding
      scale regular insulin.

PMID- 29019716
TI  - SUBCLINICAL IMPAIRMENT OF LEFT VENTRICULAR LONGITUDINAL FUNCTION IN PATIENTS WITH
      PROLACTINOMAS.
AB  - OBJECTIVE: Hyperprolactinemia has been associated with endothelial dysfunction
      and a wide range of cardiovascular risk factors, thus it can potentially lead to
      cardiac dysfunction. The present study was designed to interrogate our hypothesis
      that hyperprolactinemia can contribute to preclinical impaired left ventricular
      function. METHODS: Thirty-one prolactinoma patients and 60 healthy volunteers
      were prospectively recruited. Left ventricular function was evaluated using
      conventional two dimensions and M-mode echocardiography, as well as Doppler
      tissue imaging (DTI). RESULTS: The Tei index (0.45 +/- 0.06 vs. 0.41 +/- 0.03, P
      = .005) and ratio of transmitral and myocardial early diastolic velocities (E/Em;
      6.30 +/- 1.45 vs. 5.64 +/- 0.69, P = .045) were significantly higher, and septal
      systolic velocity (Sm; 9.88 +/- 1.45 vs. 11.58 +/- 1.28 cm/s, P<.001) was
      significantly lower in prolactinoma patients. Furthermore, significant motional
      abnormalities were detected in regional segments of prolactinoma patients.
      Pearson's correlation analysis revealed that prolactin level was inversely
      associated with Sm (r = -0.373, P = .009) and late diastolic phase (Am; r = 
      0.293, P = .043). Moreover, inverse correlations between prolactin and partial
      left ventricular segment wall motion were found, including the basal (r = -0.363,
      P = .014), middle (r = -0.418, P = .004), and apical segment (r = -0.574, P<.001)
      of the posterior ventricular septum. Multivariate linear regression analysis
      revealed that prolactin (beta = -0.28, 95% confidence interval -0.011 to 0, P =
      .035), as a single factor, can significantly predict decreased Sm, independent of
      traditional vascular risk factors. CONCLUSION: Our results suggest that
      subclinical cardiac dysfunction occurs in untreated prolactinoma patients and is
      characterized by impaired systolic and diastolic function of the left ventricle,
      as well as regional segment motional abnormality. ABBREVIATIONS: A = transmitral
      late diastolic velocity Am = late diastolic phase Apo = apolipoprotein DTI =
      Doppler tissue imaging E = transmitral early diastolic velocity Em = myocardial
      early diastolic velocity FMD = flow-mediated dilation HOMA-IR = homeostasis model
      assessment of insulin resistance hsCRP = high-sensitivity C-reactive protein IMT
      = intima media thickness LDL-C = low-density lipoprotein cholesterol LV = left
      ventricular PPCM = postpartum cardiomyopathy Sm = septal systolic velocity.

PMID- 29019718
TI  - Bilateral red legs as a result of vitamin B12 deficiency.

PMID- 29019717
TI  - ADDING VFA TO DXA IDENTIFIES FRACTURE RISK IN A WAY NOT DUPLICATED BY OTHER
      MEASURES.
AB  - OBJECTIVE: Published studies have demonstrated that adding vertebral fracture
      assessment (VFA) to dual-energy X-ray absorptiometry (DXA) identifies more
      patients with increased fracture risk than DXA alone. But who needs VFA? This
      study attempts to determine if some test other than VFA could duplicate the
      additional information obtained by performing VFA on all first-time patients.
      This study looked at the Fracture Risk Assessment Tool (FRAX), height loss, age,
      documented back pain, and nonvertebral fragility fractures. METHODS: VFA was
      performed on 1,259 (all) DXA patients at their first visit from March 2010
      through September 2013. All DXA and VFA results were read by the same
      International Society for Clinical Densitometry-certified clinician. RESULTS: By
      DXA alone, 44% were osteoporosis. Adding VFA increased clinical osteoporosis by
      36% of the original total patients. Eighty-three "normal bone mineral density"
      patients were changed to clinical osteoporosis. FRAX identified 53% of the
      patients with diagnosis changes. Historical height loss was not reliable.
      Increasing age correlated only weakly with clinical osteoporosis. CONCLUSION:
      These are modest numbers from a nonacademic referral practice and may not be
      typical of other populations. Thirty-six percent of our patients were
      misclassified by DXA alone, with fragility fractures already taken into account
      for T-scores of -1.5 and lower. FRAX, height loss, age, back pain, and fragility
      fractures all failed to identify many of the patients identified by VFA. Seeing
      the lateral spine images obtained by VFA influenced patients and families. VFA on
      all first-time patients should be reconsidered. ABBREVIATIONS: BMD = bone mineral
      density DXA = dual-energy X-ray absorptiometry FRAX = Fracture Risk Assessment
      Tool HL = height loss ISCD = International Society for Clinical Densitometry VF =
      vertebral fracture VFA = vertebral fracture assessment.

PMID- 29019719
TI  - An atypical case of scleroderma.

PMID- 29019720
TI  - Sustainability and transformation plans: translating the perspectives.
AB  - Each local health economy has been tasked with producing a sustainability and
      transformation plan. A health economy is a system that controls and contributes
      to health-care resource and the effects of health services on its population.
      This includes commissioners, acute providers, primary care providers, community
      services, public health and the voluntary sector. Sustainability and
      transformation plans represent a shift in the way health care is planned for in
      England. The aim of each sustainability and transformation plan is to deliver
      care within existing resource limits by improving quality of care, developing new
      models of care and improving efficiency of care provision. The tight timescales
      for production of sustainability and transformation plans mean that in most cases
      there has been limited clinical engagement; as a result many clinicians have
      limited sight, understanding or ownership of the proposals within sustainability
      and transformation plans. As sustainability and transformation plans move into
      the implementation phase, this article explores the role of the clinician in the
      ongoing design and delivery of the local sustainability and transformation plans.
      By finding the common ground between the perspectives of the clinician, the
      commissioner and system leaders, the motivation of clinicians can be aligned with
      the ambitions of the sustainability and transformation plan. The common goal of a
      sustainability and transformation plan and the necessary collaboration required
      to make it successful is discussed. Ultimately, such translation is essential:
      clinicians are intelligent, adaptive and motivated individuals who must have a
      lead role in constructing and implementing plans that transform health and social
      care.

PMID- 29019721
TI  - Vertigo in a taxi driver.

PMID- 29019722
TI  - Marie Curie: pioneer of radioactivity, twice winner of the Nobel Prize.

PMID- 29019723
TI  - Accidental hanging injuries in children: recognition and management.
AB  - Accidental hanging is rare in childhood but is often fatal. Window blind cords
      pose a particular and unique risk to young children in the UK, accounting for one
      to two deaths annually. These accidents are frequently associated with non
      adherence to the safety instructions provided by the manufacturers. Early
      discovery of the child and initiation of effective cardiopulmonary resuscitation
      at the site of the incident are likely to improve the outcome. Prolonged
      suspension, children who are pulseless at first contact by the emergency
      paramedic responder, and patients with prolonged periods of remaining in asystole
      before return of spontaneous circulation after starting cardiopulmonary
      resuscitation are unlikely to have intact neurological survival. Management in
      the hospital includes early airway protection by intubation, maintenance of
      normal oxygen saturation, normothermia, active control of clinical and sub
      clinical seizures, and strict electrolyte and glucose regulation. Child
      safeguarding concerns should be considered when children have asphyxial injuries,
      and other signs of child physical abuse should be actively looked for. There is a
      need for stronger legislation in the UK to prevent some of these accidents,
      especially those relating to window blind cords.

PMID- 29019724
TI  - Health economics of cardiac resynchronization therapy.

PMID- 29019725
TI  - Pre-empting project failure by using a pre-mortem.
AB  - In health care, a post-mortem might be required after a patient has died, to try
      and establish why, and sometimes when and how, the patient died. Many projects
      are likely to fail, with reasons including the lack of tools to facilitate
      change, and failure to consider the organizational and environmental situation a
      change project faces. When projects or initiatives fail, clinicians often carry
      out a 'post-mortem', trying to understand the factors that contributed to the
      failure, with the aim of learning lessons and not repeating the same mistakes.
      This article discusses the management technique known as the 'pre-mortem', with
      application of tools and strategies to help mitigate the risks of a change
      leading to failure.

PMID- 29019726
TI  - Dilemmas in the management of venous thromboembolism in older patients.
AB  - Venous thromboembolism most commonly affects older patients. Despite the high
      incidence in this population, challenges remain in terms of the understanding of
      its presentation, diagnosis and management. Old age is associated with multi
      morbidities which may complicate the diagnosis of venous thromboembolism as signs
      or symptoms may be attributed to underlying medical conditions. The presence of
      certain comorbidities (such as congestive cardiac failure and chronic obstructive
      pulmonary disease) also increases the risk of venous thromboembolism, but could
      mimic the clinical features of pulmonary embolism. In addition, the physiological
      processes associated with ageing and factors such as immobility and malignancy,
      which are more common in older people, will further increase the thrombotic risk.
      Dilemmas also exist with treatment decisions because of the concomitant increased
      risk of bleeding, comorbidities, polypharmacy, frailty and the risk of falls.

PMID- 29019728
TI  - Mastoidectomy in a child with chronic granulomatous disease.

PMID- 29019729
TI  - Enhanced recovery: pathways to better care.

PMID- 29019730
TI  - Sedation in intensive care: should we reach for dexmedetomidine sooner?

PMID- 29019731
TI  - The NHS must achieve better value from musculoskeletal services.

PMID- 29019733
TI  - Late onset myasthenia gravis and carcinoid tumour: paraneoplastic syndrome?

PMID- 29019732
TI  - The relevance of the coagulation screen before surgery.
AB  - Coagulation testing has long been part of the routine assessment of the
      preoperative patient, with the aim of identifying those with a bleeding disorder
      who might suffer significant perioperative bleeding. Some of the issues
      surrounding this involve the low prevalence of bleeding disorders in the general
      population, and the implications of further testing for both the patient and the
      health-care system. Studies suggest that this practice is not evidence based and
      is considered to be outdated. Most guidelines now advise against routine
      coagulation screens before surgery, and instead recommend taking a thorough
      personal and family history of bleeding in order to determine the need for
      further investigations. This review analyses current evidence on this topic and
      provides a comprehensive view of the relevance of preoperative coagulation
      testing.

PMID- 29019734
TI  - Failed titration of endocrine replacement therapy: diagnostic significance.
AB  - Unsuccessful titration of endocrine replacement therapy may signify the
      coexistence of an unrecognized disorder which alters the response to replacement
      therapy. Examples include recurrent hypoglycaemia when type 1 diabetes mellitus
      coexists with either Addison's disease or coeliac disease. Recurrent Addisonian
      crisis occurs when Addison's disease coexists with thyrotoxicosis. Conversely, in
      a patient with Addison's disease, recognition and treatment of coexisting coeliac
      disease may facilitate a reduction in corticosteroid dosage.

PMID- 29019735
TI  - A new cross-speciality educational collaboration in perioperative medicine.

PMID- 29019736
TI  - Clinical and laboratory assessment of a patient with thrombocytosis.
AB  - Elevated platelet counts are frequently encountered in hospital medicine and
      arise from both physiological and pathological mechanisms. Thrombocytosis may be
      secondary, reflecting an inflammatory state, iron deficiency, recent surgery or
      point towards an underlying neoplasm. Thrombocytosis may be the presenting sign
      of solid tumours and haematological conditions. The discovery of the activating
      mutations affecting thrombopoiesis led to greater understanding of the
      pathobiology of essential thrombocythaemia and other myeloproliferative
      neoplasms. The investigation of suspected primary thrombocytosis has evolved to
      include testing for these disease-associated mutations. Therapy for patients with
      essential thrombocythaemia aims to reduce their risk of thrombotic complications
      by addressing cardiovascular risk factors, and using antiplatelet agents and, in
      selected patients, cytoreductive therapy. This article provides a logical
      approach to distinguishing reactive or secondary thrombocytosis from
      thrombocytosis associated with an underlying myeloproliferative neoplasm and
      gives an overview of the management of essential thrombocythaemia.

PMID- 29019737
TI  - Clinical News.

PMID- 29019738
TI  - Frailty on the acute medical unit.

PMID- 29019739
TI  - Purpura.

PMID- 29019740
TI  - Hospital care for people with learning disability.

PMID- 29019741
TI  - Activation of mTORC1 Signaling is Required for Timely Hair Follicle Regeneration
      from Radiation Injury.
AB  - Transit amplifying cells (TACs) are highly proliferative in nature and tend to be
      sensitive to ionizing radiation. Due to the abundance of TACs that support the
      elongation of hair shafts, growing hair follicles are highly sensitive to
      radiation injury. How hair follicles repair themselves after radiation injury is
      unclear. In this study, we observed that in 4 Gy irradiated mice, hair follicle
      dystrophy was induced with apoptosis-driven loss of hair matrix cells, which are
      the TACs that fuel hair growth. The dystrophy was repaired within 96 h without
      significant hair loss, indicating that a regenerative attempt successfully
      restored the TAC population to resume anagen growth. Soon after irradiation,
      mTORC1 signaling was activated in the TAC compartment and its activation was
      maintained until the regeneration process was completed. Inhibition of mTORC1 by
      rapamycin treatment increased radiation-induced cell apoptosis, reduced cell
      proliferation and delayed restoration of Wnt signaling in the hair matrix after
      radiation injury, leading to prolonged dystrophy and hair loss. These results
      demonstrate that mTORC1 signaling is activated after irradiation and is required
      for timely regeneration of the TAC pool of hair follicles, so that hair growth
      can resume after radiation injury.

PMID- 29019742
TI  - The Impact of Hypoxia on Out-of-Field Cell Survival after Exposure to Modulated
      Radiation Fields.
AB  - Advanced radiotherapy techniques such as intensity modulated radiation therapy
      achieve highly conformal dose distributions within target tumor volumes through
      the sequential delivery of multiple spatially and temporally modulated radiation
      fields and have been shown to influence radiobiological response. The goals of
      this study were to determine the effect of hypoxia on the cell survival responses
      of different cell models (H460, DU145, A549, MDA231 and FADU) to modulated fields
      and to characterize the time dependency of signaling under oxic conditions,
      following reoxygenation and after prolonged hypoxia. Hypoxia was induced by
      incubating cells at 95% nitrogen and 5% carbon dioxide for 4 h prior to
      irradiation. The out-of-field response in MDA231 cells was oxygen dependent and
      therefore selected for co-culture studies to determine the signaling kinetics at
      different time intervals after irradiation under oxic and hypoxic conditions.
      Under both oxic and hypoxic conditions, significant increases in cell survival
      were observed in-field with significant decreases in survival observed out-of
      field (P < 0.05), which were dependent on intercellular communication. The in
      field response of MDA231 cells showed no significant time dependency up to 24 h
      postirradiation, while out-of-field survival decreased significantly during the
      first 6 h postirradiation (P < 0.05). While in-field responses were oxygen
      dependent, out-of-field effects were observed to be independent of oxygen, with
      similar or greater cell killing under hypoxic conditions. This study provides
      further understanding of intercellular signaling under hypoxic conditions and
      highlights the need for further refinement of established radiobiological models
      for future applications in advanced radiotherapies.

PMID- 29019743
TI  - Injury prevention in male youth soccer: Current practices and perceptions of
      practitioners working at elite English academies.
AB  - Forty-one practitioners inclusive of physiotherapists, sports scientists and
      strength and conditioning coaches from the academies of elite soccer clubs in the
      United Kingdom completed an on-line questionnaire which examined their: (1)
      background information; (2) perceptions of injury occurrence and risk factors;
      (3) screening and return to play; and (4) approach to designing and delivering
      injury prevention programmes with a response rate of 55% (41/75). Contact
      injuries were the most common mechanism reported and players between 13-16 years
      of age were perceived to be at the greatest risk. Pertinent risk factors
      included: reduced lower limb and eccentric hamstring strength, proprioception,
      muscle imbalances, and under developed foundational movement skills. Joint range
      of motion, jump tests, the functional movement screen, overhead and single leg
      squats were the most utilised screening methods. Training modalities rated in
      order of importance included: resistance training, flexibility development,
      agility, plyometrics and balance training. Training frequency was most commonly
      once or twice per week, during warm-ups, independent sessions or a combination of
      both. Injury prevention strategies in this cohort appear to be logical; however,
      the classification of injury occurrence and application of screening tools to
      identify "at risk" players do not align with existing research. The frequency and
      type of training used may also be insufficient to elicit an appropriate stimulus
      to address pertinent risk factors based on current recommendations.

PMID- 29019744
TI  - Pediatric Liver Transplant: Techniques and Complications.
AB  - Liver transplant is considered to be the last-resort treatment approach for
      pediatric patients with end-stage liver disease. Despite the remarkable advance
      in survival rates, liver transplant remains an intricate surgery with significant
      morbidity and mortality. Early diagnosis of complications is crucial for patient
      survival but is challenging given the lack of specificity in clinical
      presentation. Knowledge of the liver and vascular anatomy of the donor and the
      recipient or recipients before surgery is also important to avoid complications.
      In this framework, radiologists play a pivotal role on the multidisciplinary team
      in both pre- and postoperative scenarios by providing a road map to guide the
      surgery and by assisting in diagnosis of complications. The most common
      complications after liver transplant are (a) vascular, including the hepatic
      artery, portal vein, hepatic veins, and inferior vena cava; (b) biliary; (c)
      parenchymal; (d) perihepatic; and (e) neoplastic. The authors review surgical
      techniques, the role of each imaging modality, normal posttransplant imaging
      features, types of complications after liver transplant, and information required
      in the radiology report that is critical to patient care. They present an
      algorithm for an imaging approach for pediatric patients after liver transplant
      and describe key points that should be included in radiologic reports in the pre-
      and postoperative settings. Online supplemental material is available for this
      article. (c)RSNA, 2017.

PMID- 29019745
TI  - Imaging of Nonmalignant Adrenal Lesions in Children.
AB  - The adrenal glands in children can be affected by a variety of benign lesions.
      The diagnosis of adrenal lesions can be challenging, but assessment of
      morphologic changes in correlation with the clinical presentation can lead to an
      accurate diagnosis. These lesions can be classified by their cause: congenital
      (eg, discoid adrenal gland, horseshoe adrenal gland, and epithelial cysts),
      vascular and/or traumatic (eg, adrenal hemorrhage), infectious (eg, granulomatous
      diseases), enzyme deficiency disorders (eg, congenital adrenal hyperplasia [CAH]
      and Wolman disease), benign neoplasms (eg, pheochromocytomas, ganglioneuromas,
      adrenal adenomas, and myelolipomas), and adrenal mass mimics (eg, extralobar
      sequestration and extramedullary hematopoiesis). Multimodality cross-sectional
      imaging helps to define the origin, extent, and relationship of these lesions to
      adjacent structures, as well as to guide treatment management. The anatomic and
      functional imaging modalities used to evaluate pediatric adrenal lesions include
      ultrasonography, computed tomography (CT), magnetic resonance imaging, and iodine
      123 metaiodobenzylguanidine scintigraphy. Identifying the imaging features of
      nonmalignant adrenal lesions is helpful to distinguish these lesions from
      malignant adrenal neoplasms. Identifying characteristic imaging findings (eg,
      enlarged adrenal glands, with cerebriform surface, and stippled echogenicity in
      CAH; a T2-hyperintense mass with avid contrast enhancement in pheochromocytoma;
      low CT attenuation [<10 HU] and signal intensity drop on opposed-phase chemical
      shift images in adenoma; and enhancing suprarenal mass supplied by a systemic
      feeding artery in extralobar sequestration) can aid in making the correct
      diagnosis. In addition, clinical features (eg, ambiguous genitalia in CAH and
      hypertension in pheochromocytoma) can also guide the radiologist toward the
      correct diagnosis. (c)RSNA, 2017.

PMID- 29019746
TI  - Invited Commentary on "Central Nervous System Effects of Intrauterine Zika Virus
      Infection".

PMID- 29019747
TI  - Masses of the Nose, Nasal Cavity, and Nasopharynx in Children.
AB  - A wide range of masses develop in the nose, nasal cavity, and nasopharynx in
      children. These lesions may arise from the nasal ala or other structures of the
      nose, including the mucosa covering any surface of the nasal cavity, the
      cartilaginous or osseous portion of the nasal septum, the nasal turbinates, and
      the nasal bones. Lesions may also arise from the nasopharynx or adjacent
      structures and involve the nose by way of direct extension. The causes of nasal
      masses in children include congenital and developmental disorders such as
      congenital nasolacrimal duct mucocele, dermoid cyst, cephalocele, and nasal
      neuroglial heterotopia; inflammatory and infectious processes such as mucocele,
      polyp, and pyogenic granuloma; benign neoplasms such as infantile hemangioma and
      juvenile nasopharyngeal angiofibroma; malignant lesions such as rhabdomyosarcoma
      and nasopharyngeal carcinoma; and masses related to prior trauma such as septal
      hematoma. Although direct visualization, without imaging, is frequently
      sufficient to diagnose pediatric nasal conditions, in many cases imaging has a
      key role in the treatment of the affected child. Some of these lesions have
      characteristic computed tomography and/or magnetic resonance imaging findings,
      some of them are diagnosed on the basis of the location and imaging findings
      combined, and others demonstrate nonspecific imaging findings. However, imaging
      is important for better defining the total extent of the lesion and guiding the
      clinician in determining whether medical and/or surgical intervention is
      required. In this article, the authors review the imaging findings of the most
      common causes-and many of the not-so-common causes-of nasal masses encountered in
      the pediatric population. (c)RSNA, 2017.

PMID- 29019748
TI  - Doppler US in the Evaluation of Fetal Growth and Perinatal Health.
AB  - Fetal growth restriction is commonly defined as an estimated fetal weight (EFW)
      that is below the 10th percentile for gestational age. It is associated with an
      increased risk of intrauterine demise, neonatal morbidity, and neonatal death;
      therefore, antenatal detection and surveillance with the optimization of delivery
      timing are necessary to improve pregnancy outcomes. If the estimated due date has
      been verified and the EFW is below the 10th percentile for gestational age, the
      underlying cause should be investigated, since the clinical management, outcome,
      and counseling options are largely dependent on the cause of the growth
      restriction. Serial ultrasonography (US) for the evaluation of fetal growth and
      umbilical artery Doppler velocimetry are used to guide pregnancy management
      decisions. This article describes the accurate US detection and surveillance of
      fetal growth restriction, discusses the current obstetric and radiology
      literature regarding the use of Doppler velocimetry in the setting of fetal
      growth restriction, and describes the techniques for performing umbilical artery
      Doppler velocimetry. Although various Doppler techniques have been described in
      the setting of fetal growth restriction, only umbilical artery Doppler assessment
      is recommended to identify fetuses most at risk for poor outcome and to guide the
      timing of delivery. The use of other Doppler waveforms in this setting remains
      investigational. (c)RSNA, 2017.

PMID- 29019749
TI  - Pearls and Pitfalls in Diagnosing Pediatric Urinary Bladder Masses.
AB  - Urinary bladder masses are rare in children, and the associated histologic
      features and prognoses in this population are different from those in adults.
      Most children with urinary bladder masses present with lower urinary tract
      symptoms, which may include hematuria, dysuria, frequent urination, and urgency
      to urinate. However, some of these masses may be identified incidentally or
      involve generic symptoms such as abdominal distention. In general, pediatric
      bladder tumors can be divided into those that originate from the bladder
      epithelium, known as urothelial neoplasms, and mesenchymal bladder neoplasms,
      which are more prevalent. The most common bladder malignancy in children is a
      rhabdomyosarcoma, whereas the most common benign bladder lesion in the pediatric
      population is a papillary urothelial neoplasm of low malignant potential
      (PUNLMP). The first-line imaging tool for assessing bladder lesions is
      ultrasonography, which may be followed by a cross-sectional imaging examination
      such as computed tomography or magnetic resonance imaging if the origin of the
      mass is unclear or if distant spread is suspected. Although imaging may enable
      the radiologist to suggest a differential diagnosis based on lesion location and
      patient age, tissue biopsy generally is required to identify the exact pathologic
      entity. This is usually performed at cystoscopy and may be curative in cases in
      which the lesion is small and has low recurrence potential. Knowledge of the
      clinical, histopathologic, and imaging features of common bladder neoplasms is
      essential, as it can aid in preventing imaging pitfalls. These may include the
      misinterpretation of either a pelvic mass as arising from the bladder or a
      bladder mass as arising from the pelvis, and interpreting an inflammatory mass or
      bladder detritus as a neoplasm. (c)RSNA, 2017.

PMID- 29019750
TI  - Contrast-enhanced US Assessment of Focal Liver Lesions in Children.
AB  - Ultrasonography (US) is often the first line of imaging for the examination of
      children suspected of having liver lesions. However, gray-scale US with color
      Doppler imaging has limitations. The use of US contrast agents has recently been
      approved by the U.S. Food and Drug Administration (FDA). Compared with other
      imaging modalities, contrast material-enhanced US (CEUS) enables the assessment
      of contrast enhancement patterns with a higher temporal resolution and is
      therefore becoming a valuable alternative imaging technique. CEUS is advantageous
      owing to its high safety profile; lower cost, compared with the costs of
      conventional contrast-enhanced computed tomographic and magnetic resonance
      imaging examinations; reliability; and reproducibility. Furthermore, US
      examinations obviate the use of sedation, ionizing radiation, and iodinated or
      gadolinium-based contrast agents. All of these are desirable attributes for an
      imaging examination for children, the most vulnerable of patients. Focal liver
      lesions in children are commonly discovered incidentally, and this can pose a
      dilemma in terms of diagnosis and management. Owing to the FDA's recent approval
      of the use of a specific US contrast agent for evaluation of focal liver lesions
      in pediatric patients, CEUS can now be used as a problem-solving tool that
      complements conventional imaging examinations and aids in the follow-up of
      lesions. The temporal resolution with CEUS enables US images to readily depict
      the real-time internal vascularity of a lesion. The characterization of a lesion
      during different phases of enhancement improves diagnostic confidence and
      treatment. In this article, the authors review the composition, physiologic
      properties, and safety profile of CEUS; describe the technique for performing
      CEUS; and highlight the utility of this examination in the assessment of common
      focal liver lesions in children. Online supplemental material is available for
      this article. (c)RSNA, 2017.

PMID- 29019751
TI  - The 2017 RadioGraphics Monograph Issue: Pediatric Imaging.

PMID- 29019752
TI  - Invited Commentary: Prime Time for Contrast-enhanced Voiding Urosonography after
      Approval of a US Contrast Agent for Children.

PMID- 29019753
TI  - Imaging of Pediatric Growth Plate Disturbances.
AB  - The growth plates, or physes, are visible on virtually all images obtained in
      skeletally immature children. The proper function of these growth plates depends
      on an intricate balance between chondrocyte proliferation, which requires
      nourishment from the epiphyseal vessels, and chondrocyte death, which requires
      the integrity of the metaphyseal vessels. Therefore, injury to the growth plate
      (ie, direct insult) or vascular compromise on either side of the growth plate
      (ie, indirect insult) can cause growth plate dysfunction. Direct growth plate
      insults occur most commonly with Salter-Harris fractures, and injuries that allow
      the transphyseal communication of vessels are at a higher risk for subsequent
      transphyseal bone bridge formation. Indirect insults lead to different sequelae
      that are based on whether the epiphyseal blood supply or metaphyseal blood supply
      is compromised. Epiphyseal osteonecrosis can result in slowed longitudinal bone
      growth, with possible growth plate closure, and is often accompanied by an
      abnormal secondary ossification center. In contrast, the disruption of
      metaphyseal blood supply alters endochondral ossification and allows the
      persistence of chondrocytes within the metaphysis, which appear as focal or
      diffuse growth plate widening. Imaging remains critical for detecting acute
      injuries and identifying subsequent growth disturbances. Depending on the imaging
      findings and patient factors, these growth disturbances may be amenable to
      conservative or surgical treatment. Therefore, an understanding of the anatomy
      and physiologic features of the normal growth plate and the associated
      pathophysiologic conditions can increase diagnostic accuracy, enable radiologists
      to anticipate future growth disturbances, and ensure optimal imaging, with the
      ultimate goal of timely and appropriate intervention. (c)RSNA, 2017.

PMID- 29019754
TI  - Abnormalities of the Coronary Arteries in Children: Looking beyond the Origins.
AB  - Coronary arterial abnormalities are uncommon findings in children that have
      profound clinical implications. Although anomalies of the coronary origins are
      well described, there are many other disease processes that affect the coronary
      arteries. Immune system-mediated diseases (eg, Kawasaki disease, polyarteritis
      nodosa, and other vasculiditides) can result in coronary arterial aneurysms,
      strictures, and abnormal tapering of the vessels. Because findings at imaging are
      an important component of diagnosis in these diseases, the radiologist's
      understanding of them is essential. Congenital anomalies may present at varying
      ages, and findings in hemodynamically significant anomalies, such as fistulas,
      are key for both diagnosis and preoperative planning. Pediatric heart surgery can
      result in wide-ranging postoperative imaging appearances of the coronary arteries
      and also predisposes patients to a multitude of complications affecting the heart
      and coronary arteries. In addition, although rare, accidental trauma can lead to
      injury of the coronary arteries, and awareness and detection of these conditions
      are important for diagnosis in the acute setting. Patients with coronary arterial
      conditions at presentation may range from being asymptomatic to having findings
      of myocardial infarction. Recognition of the imaging findings is essential to
      direct appropriate treatment. (c)RSNA, 2017.

PMID- 29019755
TI  - Interstitial Lung Disease in Children Made Easier...Well, Almost.
AB  - Interstitial lung disease (ILD) in pediatric patients is different from that in
      adults, with a vast array of pathologic conditions unique to childhood, varied
      modes of presentation, and a different range of radiologic appearances. Although
      rare, childhood ILD (chILD) is associated with significant morbidity and
      mortality, most notably in conditions of disordered surfactant function, with
      respiratory failure in 100% of neonates with surfactant protein B dysfunction and
      100% mortality without lung transplantation. The authors present a summary of
      lung development and anatomy, followed by an organized approach, using the
      structure and nomenclature of the 2013 update to the chILD Research Network
      classification system, to aid radiologic diagnosis of chILD. Index radiologic
      cases with contemporaneous histopathologic findings illustrate a summary of
      recent imaging studies covering the full spectrum of chILD. chILD is best grouped
      by age at presentation from infancy (diffuse developmental disorders, lung growth
      abnormalities, specific conditions of unknown origin, surfactant dysfunction
      mutations) to later childhood (disorders of the normal host, disorders related to
      systemic disease processes, disorders related to immunocompromise). Appreciation
      of the temporal division of chILD into infant and later childhood onset, along
      with a sound understanding of pulmonary organogenesis and surfactant homeostasis,
      will aid in providing useful insight into this important group of pediatric
      conditions. Application of secondary lobular anatomy to interpretation of thin
      section computed tomographic images is pivotal to understanding patterns of ILD
      and will aid in selecting and narrowing a differential diagnosis. (c)RSNA, 2017.

PMID- 29019756
TI  - Imaging of Skeletal Disorders Caused by Fibroblast Growth Factor Receptor Gene
      Mutations.
AB  - Fibroblast growth factors and fibroblast growth factor receptors (FGFRs) play
      important roles in human axial and craniofacial skeletal development. FGFR1,
      FGFR2, and FGFR3 are crucial for both chondrogenesis and osteogenesis. Mutations
      in the genes encoding FGFRs, types 1-3, are responsible for various skeletal
      dysplasias and craniosynostosis syndromes. Many of these disorders are relatively
      common in the pediatric population, and diagnosis is often challenging. These
      skeletal disorders can be classified based on which FGFR is affected. Skeletal
      disorders caused by type 1 mutations include Pfeiffer syndrome (PS) and
      osteoglophonic dysplasia, and disorders caused by type 2 mutations include
      Crouzon syndrome (CS), Apert syndrome (AS), and PS. Disorders caused by type 3
      mutations include achondroplasia, hypochondroplasia, thanatophoric dysplasia
      (TD), severe achondroplasia with developmental delay and acanthosis nigricans,
      Crouzonodermoskeletal syndrome, and Muenke syndrome. Most of these mutations are
      inherited in an autosomal dominant fashion and are gain-of-function-type
      mutations. Imaging plays a key role in the evaluation of these skeletal
      disorders. Knowledge of the characteristic imaging and clinical findings can help
      confirm the correct diagnosis and guide the appropriate molecular genetic tests.
      Some characteristics and clinical findings include premature fusion of cranial
      sutures and deviated broad thumbs and toes in PS; premature fusion of cranial
      sutures and syndactyly of the hands and feet in AS; craniosynostosis, ocular
      proptosis, and absence of hand and foot abnormalities in CS; rhizomelic limb
      shortening, caudal narrowing of the lumbar interpediculate distance, small and
      square iliac wings, and trident hands in achondroplasia; and micromelia, bowing
      of the femora, and platyspondyly in TD. (c)RSNA, 2017.

PMID- 29019757
TI  - Pediatric Ovarian Torsion: Spectrum of Imaging Findings.
AB  - The accurate diagnosis of ovarian torsion is imperative, as loss of the ovary can
      have long-term consequences in terms of fertility. However, a nonspecific
      clinical presentation in conjunction with a highly variable imaging appearance
      makes the diagnosis of ovarian torsion challenging. This is complicated even
      further in the pediatric population, as these patients cannot always articulate
      their symptoms or provide an adequate medical history. Therefore, imaging has a
      critical role in the diagnosis of ovarian torsion in pediatric patients. Common
      imaging findings of ovarian torsion in the prepubescent and adolescent
      populations include asymmetric enlargement of the ovary, peripheral location of
      ovarian follicles, and midline location of the ovary. A coexistent mass within
      the ovary may or may not be present. Antenatal torsion also can occur and may be
      discovered at routine or specific imaging of the fetus or postnatal imaging of
      the neonate. Imaging findings in the perinatal population that may suggest
      torsion include a cystic mass with a fluid-debris level and a complex,
      multiseptated mass. This article reviews ovarian torsion throughout the pediatric
      years-from the fetal period through adolescence. It reviews the clinical
      presentation and imaging findings of this abnormality while describing the
      relevant anatomy, embryologic features, and pathophysiology. Ovarian torsion may
      be variable in appearance owing to the age and degree of torsion, which is seen
      early as a large ovary with peripheral follicles and later, once necrosis has
      ensued, as a complex cystic mass. (c)RSNA, 2017.

PMID- 29019758
TI  - Sonographic Evaluation of Pediatric Thyroid Nodules.
AB  - A thyroid nodule detected clinically or incidentally at medical imaging is a
      common indication for ultrasonography (US) in the adult population. This scenario
      is less frequently the case in pediatric patients, and the approach to evaluation
      of thyroid nodules deserves modification in these patients because of the
      increased probability of malignancy in children, compared with adults. Evaluating
      a thyroid nodule with US in a systematic way requires familiarity with a number
      of features that can be assessed and the terms that the radiologist uses in each
      category. The probability of malignancy is influenced by certain features, and
      several models have emerged to integrate these details into an overall risk
      assessment to guide management and biopsy of thyroid nodules. Clinical features
      of thyroid cancer differ between pediatric and adult patients, and risk factors
      and certain genetic syndromes portend earlier manifestation of thyroid
      malignancy. This article provides a review of (a) US features of thyroid nodules
      with an emphasis on the predictive capacity for malignancy, focused on the
      pediatric age group when the data exist, (b) clinical information, including risk
      factors and genetic syndromes pertinent to the pediatric population, and (c) the
      state of the current literature and controversies in diagnosing and managing
      pediatric thyroid cancer. (c)RSNA, 2017.

PMID- 29019759
TI  - Non-Catheter-related Venous Thromboembolism in Children: Imaging Review from Head
      to Toe.
AB  - Non-catheter-related venous thromboembolism (VTE) is less common in children than
      in adults. Although the presence of a central venous catheter is the most common
      cause of venous thrombosis in children, infection and inflammation, malignancy,
      hypercoagulability, dehydration, and certain sites of normal variant and
      pathologic anatomic narrowing all predispose to VTE in children. The mortality
      and morbidity of VTE vary according to the underlying cause, including whether
      malignancy is present. Various modalities including ultrasonography (US),
      computed tomography, and magnetic resonance imaging can be used to image VTE,
      with some modalities better suited to particular parts of the body and clinical
      scenarios than others. When feasible, US is the initial test of choice for the
      diagnosis of VTE. US findings of acute VTE include a dilated noncompressible
      vein, intraluminal echoes, lack of color flow, and abnormal spectral venous
      waveforms. Serial US examinations are useful for monitoring patient response to
      therapy; a normal compressible vein will be seen after complete resolution of
      thrombus, and chronic venous changes including wall thickening, intraluminal
      webs, and phleboliths, which are readily apparent at US. Accurate and timely
      diagnosis of VTE must take into account the various advantages and disadvantages
      of each modality including speed, accuracy, availability, exposure to ionizing
      radiation, and need for sedation, as well as the clinical stability and
      transportability of the child. This article reviews some of the more common
      causes of VTE in children (other than those related to a central venous catheter)
      according to body part and discusses the associated imaging findings. (c)RSNA,
      2017.

PMID- 29019760
TI  - MR Lymphangiography in Children: Technique and Potential Applications.
AB  - The lymphatic system, an important component of the circulatory system with
      essential physiologic functions, can be affected by various disease processes.
      There has been a delay in the development of effective imaging methods for the
      lymphatic system due to its small size, which limits visualization as well as
      introduction of contrast material. Traditionally, the lymphatic system has been
      imaged by injecting contrast material or radiotracers into the feet or hands.
      This is not sufficient for assessment of the central conducting lymphatics (CCLs)
      (such as the thoracic duct or the cisterna chyli). Fluoroscopic intranodal
      lymphangiography with injection of oil-based contrast material into groin lymph
      nodes improves visualization of CCLs but is limited in practice owing to the use
      of radiation and the potential risk for paradoxical embolization in children with
      left-to-right shunt. Dynamic contrast material-enhanced (DCE) magnetic resonance
      (MR) lymphangiography, which is performed by injecting gadolinium-based contrast
      material into groin lymph nodes, overcomes these limitations. T2-weighted imaging
      plays a complementary role to DCE MR lymphangiography in the assessment of CCLs.
      DCE MR lymphangiography demonstrates preserved integrity or any abnormality of
      the CCLs (including blockage or leak). The technique has recently been used in
      evaluating pulmonary lymphatic perfusion syndrome in children with plastic
      bronchitis, neonatal lymphatic flow disorders, and nontraumatic chylothorax. It
      is useful in identification of the source of chylous ascites and contributes to
      understanding of the anatomy of lymphatic malformations. It is successfully used
      for planning of embolization of aberrant lymphatic channels in a variety of
      lymphatic flow disorders. This review discusses the anatomy and function of the
      lymphatic system, the evolution of imaging of the lymphatic system, and DCE MR
      lymphangiography technique and its applications in children. (c)RSNA, 2017.

PMID- 29019761
TI  - Contrast-enhanced Voiding Urosonography for Vesicoureteral Reflux Diagnosis in
      Children.
AB  - Contrast-enhanced voiding urosonography (ceVUS) is a dynamic imaging technique
      that makes it possible to study the structure of the urinary tract after the
      administration of intravesical contrast material. Initially, ceVUS was indicated
      mainly to study vesicoureteral reflux (VUR); however, since the ability of ceVUS
      to depict the structure of the urethra was demonstrated in both sexes, ceVUS is
      now indicated for examination of the entire urinary tract. The main benefit of
      ceVUS is that it does not use ionizing radiation. In recent years, fundamental
      changes have occurred in the understanding of VUR. The lessening effect of VUR
      and the low rate of occurrence of urethral pathologic conditions have given rise
      to changes in the indications for tests for these conditions. In addition to
      being able to help confirm a diagnosis of VUR, the ceVUS technique can be used to
      depict obstructive and nonobstructive urethral pathologic conditions, as well as
      normal variants, on high-quality images. Furthermore, ceVUS enables real-time
      assessment of voiding function. For these reasons, ceVUS should be not only an
      alternative to voiding cystourethrography, but also the technique of choice for
      the study of the entire urinary tract in pediatric patients. Online supplemental
      material is available for this article. (c)RSNA, 2017.

PMID- 29019763
TI  - Trends in Autism Spectrum Disorders: The Interaction of Time, Group-Level
      Socioeconomic Status, and Individual-Level Race/Ethnicity.

PMID- 29019764
TI  - Henry E. Sigerist (1891- 1957): Medical Historian, Advocate of "Socialized"
      Medicine, and Admirer of the Soviet Health System.

PMID- 29019762
TI  - Central Nervous System Effects of Intrauterine Zika Virus Infection: A Pictorial
      Review.
AB  - Relatively few agents have been associated with congenital infections involving
      the brain. One such agent is the Zika virus, which has caused several outbreaks
      worldwide and has spread in the Americas since 2015. The Zika virus is an
      arbovirus transmitted by infected female mosquito vectors, such as the Aedes
      aegypti mosquito. This virus has been commonly associated with congenital
      infections of the central nervous system and has greatly increased the rates of
      microcephaly. Ultrasonography (US) remains the method of choice for fetal
      evaluation of congenital Zika virus infection. For improved assessment of the
      extent of the lesions, US should be complemented by magnetic resonance (MR)
      imaging. Postnatal computed tomography and MR imaging can also unveil additional
      findings of central nervous system involvement, such as microcephaly with
      malformation of cortical development, ventriculomegaly, and multifocal
      calcifications in the cortical-subcortical junction, along with associated
      cortical atrophy. The calcifications may be punctate, dystrophic, linear, or
      coarse and may follow a predominantly bandlike distribution. A small anterior
      fontanelle with prematurely closed sutures is also observed with Zika virus
      infection. In this review, the prenatal and postnatal neurologic imaging findings
      of congenital Zika virus infection are covered. Radiologists must be aware of
      this challenging entity and have knowledge of the various patterns that may be
      depicted with each imaging modality and the main differential diagnosis of the
      disease. As in other neurologic infections, serial imaging is able to help
      demonstrate the progression of the findings. (c)RSNA, 2017.

PMID- 29019765
TI  - Assessing the Public Health Impact of the mHealth App Business.

PMID- 29019766
TI  - Screening for Food Insecurity: Short-Term Alleviation and Long-Term Prevention.

PMID- 29019767
TI  - Health: An Optimal Commodity for the Attention Economy.

PMID- 29019768
TI  - Deregulation, Devolution, and State Preemption Laws' Impact on US Mortality
      Trends.

PMID- 29019770
TI  - Quite Outside Our Imagination: Alan Gregg Diary Entries During His Trip to the
      Soviet Union, December 1927.

PMID- 29019769
TI  - Abortion Is Not Just About the Role of Women in Society, but Also the Role of
      Religion.

PMID- 29019771
TI  - On the Promise and Peril of Technology for Population Health: A Public Health of
      Consequence, November 2017.

PMID- 29019772
TI  - Advancing Science and Public Health Practice on Climate Change and Health
      Justice.

PMID- 29019773
TI  - Our Greedy Health Care System.

PMID- 29019775
TI  - AJPH Global News.

PMID- 29019774
TI  - Anti-Tobacco Propaganda: Soviet Union Versus Nazi Germany.

PMID- 29019776
TI  - Two Sides of the Crisis.

PMID- 29019777
TI  - The Physicians' Case for Marijuana Legalization.

PMID- 29019779
TI  - Can the FDA Help Reduce Drug Prices or the Cost of Medical Care?

PMID- 29019780
TI  - The Promises, Realities, and Legacies of the Bolshevik Revolution, 1917-2017.

PMID- 29019783
TI  - Advancing Suicide Prevention Through a Focus on Firearm Safety.

PMID- 29019786
TI  - The Time Is Now for eHealth Research With Latinos.

PMID- 29019782
TI  - Recreational Cannabis Legalization and Opioid-Related Deaths in Colorado, 2000
      2015.
AB  - OBJECTIVES: To examine the association between Colorado's legalization of
      recreational cannabis use and opioid-related deaths. METHODS: We used an
      interrupted time-series design (2000-2015) to compare changes in level and slope
      of monthly opioid-related deaths before and after Colorado stores began selling
      recreational cannabis. We also describe the percent change in opioid-related
      deaths by comparing the unadjusted model-smoothed number of deaths at the end of
      follow-up with the number of deaths just prior to legalization. RESULTS:
      Colorado's legalization of recreational cannabis sales and use resulted in a 0.7
      deaths per month (b = -0.68; 95% confidence interval = -1.34, -0.03) reduction in
      opioid-related deaths. This reduction represents a reversal of the upward trend
      in opioid-related deaths in Colorado. CONCLUSIONS: Legalization of cannabis in
      Colorado was associated with short-term reductions in opioid-related deaths. As
      additional data become available, research should replicate these analyses in
      other states with legal recreational cannabis.

PMID- 29019787
TI  - Advancing the Right to Health-The Vital Role of Law.

PMID- 29019790
TI  - The Essence of the Soviet Health System.

PMID- 29019789
TI  - Mexican Cohort Study Predates but Predicts the Type of Body Composition Changes
      Expected From the Mexican Sugar-Sweetened Beverage Tax.

PMID- 29019788
TI  - Gaps in Federal and State Screening of Tuberculosis in the United States.

PMID- 29019791
TI  - The influence of dopaminergic system inhibition on biosynthesis of gonadotrophin
      releasing hormone (GnRH) and GnRH receptor in anoestrous sheep; hierarchical role
      of kisspeptin and RFamide-related peptide-3 (RFRP-3).
AB  - This study aimed to explain how prolonged inhibition of central dopaminergic
      activity affects the cellular processes governing gonadotrophin-releasing hormone
      (GnRH) and LH secretion in anoestrous sheep. For this purpose, the study included
      two experimental approaches: first, we investigated the effect of infusion of
      sulpiride, a dopaminergic D2 receptor antagonist (D2R), on GnRH and GnRH receptor
      (GnRHR) biosynthesis in the hypothalamus and on GnRHR in the anterior pituitary
      using an immunoassay. This analysis was supplemented by analysis of plasma LH
      levels by radioimmunoassay. Second, we used real-time polymerase chain reaction
      to analyse the influence of sulpiride on the levels of kisspeptin (Kiss1) mRNA in
      the preoptic area and ventromedial hypothalamus including arcuate nucleus
      (VMH/ARC), and RFamide-related peptide-3 (RFRP-3) mRNA in the paraventricular
      nucleus (PVN) and dorsomedial hypothalamic nucleus. Sulpiride significantly
      increased plasma LH concentration and the levels of GnRH and GnRHR in the
      hypothalamic-pituitary unit. The abolition of dopaminergic activity resulted in a
      significant increase in transcript level of Kiss1 in VMH/ARC and a decrease of
      RFRP-3 in PVN. The study demonstrates that dopaminergic neurotransmission through
      D2R is involved in the regulatory pathways of GnRH and GnRHR biosynthesis in the
      hypothalamic-pituitary unit of anoestrous sheep, conceivably via mechanisms in
      which Kiss1 and RFRP-3 participate.

PMID- 29019792
TI  - Prevalence and determinants of susceptibility to cigarette smoking among non
      smoking senior secondary school students in Ilorin, North Central Nigeria.
AB  - Background Globally, efforts are being made to control tobacco use. However,
      adolescents who are susceptible to cigarette smoking constitute a major challenge
      to control efforts. Defining the magnitude of susceptible adolescents and
      associated factors in any setting is critical to the development of measures that
      will successfully address this issue. This study estimated the prevalence and
      factors associated with susceptibility to cigarette smoking among non smoking
      students in Ilorin, North Central Nigeria. Methods A cross sectional study
      involving 2000 secondary school students selected via multistage sampling
      technique. Data was collected using a self administered questionnaire, while
      analysis was done using SPSS 16.0. Results Prevalence of susceptibility to
      cigarette smoking among non smoking respondents was 13.6% (14.5% among males and
      11.4% among females, respectively). Factors associated with susceptibility to
      cigarette smoking were parental smoking habit [odds ratio (OR) = 4.43], having
      close friends who smoke (OR = 6.54), engagement in vocational training (OR =
      1.39), exposure to environmental tobacco smoke at home (OR = 1.61), knowledge of
      harmful effects of tobacco (OR = 2.35) and perceptions of the effect of cigarette
      smoking such as enhancing attractive among boys (OR = 2.03), and causing weight
      gain among boys (OR = 2.39) and among girls (OR = 6.05). Conclusion The high
      prevalence of susceptibility to cigarette smoking among the non smoking students
      highlights the potential for future increase in prevalence of cigarette smoking
      in the setting. Efforts at controlling cigarette smoking will not be totally
      successful if susceptibility to cigarette smoking among adolescents is not
      addressed.

PMID- 29019793
TI  - Tuning biomimetic membrane barrier properties by hydrocarbon, cholesterol and
      polymeric additives.
AB  - The barrier properties of cellular membranes are increasingly attracting
      attention as a source of inspiration for designing biomimetic membranes. The
      broad range of potential technological applications makes the use of lipid and
      lately also polymeric materials a popular choice for constructing biomimetic
      membranes, where the barrier properties can be controlled by the composition of
      the membrane constituent elements. Here we investigate the membrane properties
      reported by the light-induced proton pumping activity of bacteriorhodopsin (bR)
      reconstituted in three vesicle systems of different membrane composition.
      Specifically we quantify how the resulting proton influx and efflux rates are
      influenced by the membrane composition using a variety of membrane modulators. We
      demonstrate that by adding hydrocarbons to vesicles with reconstituted bR formed
      from asolectin lipids the resulting transmembrane proton fluxes changes
      proportional to the carbon chain length when compared against control. We observe
      a similar proportionality in single-component 1,2-Dioleoyl-sn-glycero-3
      phosphocholine model membranes when using cholesterol. Lastly we investigate the
      effects of adding the amphiphilic di-block co-polymer polybutadiene
      polyethyleneoxide (PB12-PEO10) to phospholipid membranes formed from 1,2-Dioleoyl
      sn-glycero-3-phosphocholine, 1,2-Dioleoyl-sn-glycero-3-phosphatidylethanolamine,
      and 1,2-Dioleoyl-sn-glycero-3-phosphatidylserine. The proton pumping activity of
      bR (measured as a change in extra-vesicular pH) in mixed lipid/PB12-PEO10 lipid
      systems is up to six-fold higher compared to that observed for bR containing
      vesicles made from PB12-PEO10 alone. Interestingly, bR inserts with apparent
      opposite orientation in pure PB12-PEO10 vesicles as compared to pure lipid
      vesicles. Addition of equimolar amounts of lipids to PB12-PEO10 results in bR
      orientation similar to that observed for pure lipids. In conclusion our results
      show how the barrier properties of the membranes can be controlled by the
      composition of the membrane. In particular the use of mixed lipid-polymer systems
      may pave the way for constructing biomimetic membranes tailored for optimal
      properties in various applications including drug delivery systems, biosensors
      and energy conservation technology.

PMID- 29019794
TI  - Vessel calibre and flow splitting relationships at the internal carotid artery
      terminal bifurcation.
AB  - OBJECTIVE: Vessel lumen calibres and flow rates are thought to be related by
      mathematical power laws, reflecting the optimization of cardiac versus metabolic
      work. While these laws have been confirmed indirectly via measurement of branch
      calibres, there is little data confirming power law relationships of flow
      distribution to branch calibres at individual bifurcations. APPROACH: Flow rates
      and diameters of parent and daughter vessels of the internal carotid artery
      terminal bifurcation were determined, via robust and automated methods, from 4D
      phase-contrast magnetic resonance imaging and 3D rotational angiography of 31
      patients. MAIN RESULTS: Junction exponents were 2.06  +/-  0.44 for relating
      parent to daughter branch diameters (geometrical exponent), and 2.45  +/-  0.75
      for relating daughter branch diameters to their flow division (flow split
      exponent). These exponents were not significantly different, but showed large
      inter- and intra-individual variations, and with confidence intervals excluding
      the theoretical optimum of 3. Power law fits of flow split versus diameter ratio
      and pooled flow rates versus diameters showed exponents of 2.17 and 1.96,
      respectively. A significant negative correlation was found between age and the
      geometrical exponent (r  =  -0.55, p  =  0.003) but not the flow split exponent.
      We also found a dependence of our results on how lumen diameter is measured,
      possibly explaining some of the variability in the literature. SIGNIFICANCE: Our
      study confirms that, on average, division of flow to the middle and anterior
      cerebral arteries is related to these vessels' relative calibres via a power law,
      but it is closer to a square law than a cube law as commonly assumed.

PMID- 29019795
TI  - DIFFERENCE IN TREATMENT OUTCOMES ACCORDING TO OPTICAL COHERENCE TOMOGRAPHY-BASED
      STAGES IN TYPE 3 NEOVASCULARIZATION (RETINAL ANGIOMATOUS PROLIFERATION).
AB  - PURPOSE: To compare 12-month treatment outcomes of Type 3 neovascularization
      among its different stages as classified using an optical coherence tomography
      based method. METHODS: This retrospective observational study included 40
      patients (40 eyes) who were newly diagnosed with Type 3 neovascularization. The
      patients were initially administered 3 monthly anti-vascular endothelial growth
      factor injections. Repeat treatment was performed when recurrence of fluid was
      noted. Disease staging was classified using the optical coherence tomography
      based method. The best-corrected visual acuity at diagnosis and at 12 months and
      degree of change in best-corrected visual acuity were compared among the
      different stages of the disease. In addition, incidence of progression in the
      disease stages was estimated. RESULTS: Among the 40 patients, 14 (35.0%) were
      classified as Stage 2 and 26 (65.0%) were classified as Stage 3. The best
      corrected visual acuity values at diagnosis and at 12 months were 0.61 +/- 0.31
      (20/81 Snellen equivalents) and 0.46 +/- 0.30 (20/57) in the Stage 2 group and
      0.67 +/- 0.42 (20/93) and 0.70 +/- 0.49 (20/100) in the Stage 3 group,
      respectively. There was a significant difference in best-corrected visual acuity
      change between the two groups (P = 0.036). During the follow-up period, 3 retinal
      pigment epithelium tears and 2 submacular hemorrhages had developed in the Stage
      3 group. Progression of the disease from Stage 2 to Stage 3 was noted in 2
      patients (14.3%). CONCLUSION: The visual outcome was worse in Stage 3 than in
      Stage 2, and adverse events that may lead to abrupt visual deterioration
      developed only in Stage 3. Further studies are needed to reveal whether anti
      vascular endothelial growth factor therapy can suppress the progression of the
      disease stages.

PMID- 29019796
TI  - Monitoring modalities and assessment of fluid status: A practice management
      guideline from the Eastern Association for the Surgery of Trauma.
AB  - BACKGROUND: Fluid administration in critically ill surgical patients must be
      closely monitored to avoid complications. Resuscitation guided by invasive
      methods are not consistently associated with improved outcomes. As such, there
      has been increased use of focused ultrasound and Arterial Pulse Waveform Analysis
      (APWA) to monitor and aid resuscitation. An assessment of these methods using the
      Grading of Recommendations Assessment, Development, and Evaluation (GRADE)
      framework is presented. METHODS: A subsection of the Surgical Critical Care Task
      Force of the Practice Management Guideline Committee of EAST conducted two
      systematic reviews to address the use of focused ultrasound and APWA in surgical
      patients being evaluated for shock. Six population, intervention, comparator, and
      outcome (PICO) questions were generated. Critical outcomes were prediction of
      fluid responsiveness, reductions in organ failures or complications and
      mortality. Forest plots were generated for summary data and GRADE methodology was
      used to assess for quality of the evidence. Reviews are registered in PROSPERO,
      the International Prospective Register of Systematic Reviews (42015032402 and
      42015032530). RESULTS: Twelve focused ultrasound studies and 20 APWA
      investigations met inclusion criteria. The appropriateness of focused ultrasound
      or APWA-based protocols to predict fluid responsiveness varied widely by study
      groups. Results were mixed in the one focused ultrasound study and 9 APWA studies
      addressing reductions in organ failures or complications. There was no mortality
      advantage of either modality versus standard care. Quality of the evidence was
      considered very low to low across all PICO questions. CONCLUSION: Focused
      ultrasound and APWA compare favorably to standard methods of evaluation but only
      in specific clinical settings. Therefore, conditional recommendations are made
      for the use of these modalities in surgical patients being evaluated for shock.
      LEVEL OF EVIDENCE: Systematic Review, level II.

PMID- 29019797
TI  - The promise of mesenchymal stem cell therapy for acute respiratory distress
      syndrome.
AB  - This review describes the current state of the science on mesenchymal stem cell
      (MSC) treatment for acute lung injury (ALI). The general characteristics,
      regenerative potential, and mechanism of action of MSCs are first presented.
      Next, particular emphasis is placed on the application of MSCs for the treatment
      of acute respiratory distress syndrome (ARDS) in preclinical and clinical
      studies. Finally, we discuss current challenges and future directions in the
      field presented from a clinician-researcher perspective. The objective of this
      work is to provide the readership with a current review of the literature
      discussing the hurdles and overall promise of MSCs as therapeutic interventions
      for the treatment of ARDS.

PMID- 29019798
TI  - The Return to Literature-Making Doctors Matter in the New Era of Medicine.
AB  - The rapid explosion of medical knowledge of the 19th and 20th centuries required
      a transformation in medical education, which, to that point, had been marked by
      low educational standards. To combat the lack of regulation, the 1910 Flexner
      Report recommended sweeping reforms. By 1930, students hoping to enroll in a
      medical school would need to complete courses in chemistry, physics, and biology,
      leaving little room for the liberal arts.Medicine is once again changing. The
      impact of artificial intelligence is being felt across all medical fields, and
      the nature of physicians' jobs in the new landscape of intelligent machines will
      inevitably also have to change. What will the role of new physicians be? And how
      should medical education be amended to meet those needs?In 2017, the Georgetown
      University School of Medicine graduated the first group of students from its
      Literature and Medicine Track-the first U.S. medical school track dedicated to
      the study of literature. This Invited Commentary explores the work done in, and
      the scholarship resulting from, this novel educational program and suggests ways
      in which literature could be used to prepare future doctors for the evolving
      demands of the medical field.

PMID- 29019799
TI  - To See the Suffering.
AB  - The author notes the impressive growth in medical humanities programs, scholarly
      journals, textbooks, and national and international conferences as well as the
      convening of two recent national forums or boards addressing the potential of the
      humanities and the arts to improve medical practice. She also notes that the
      field of medical humanities seems to have shifted from addressing topics on the
      margins of medical education to equipping students with the foundational skills
      required for effective doctoring. This Invited Commentary proposes a number of
      personal, relational, and interpretive consequences to rigorous training in the
      humanities or the arts that might lead to improvement in the skills of doctoring.
      Where else but in hospitals with very ill patients and very young doctors who
      care for them are such skills needed the most? The author suggests that to see
      the suffering might be what the humanities in medicine are for, and that those
      who become capable of seeing the suffering around them in medical practice both
      experience the cost of countenancing the full burden of illness and death and,
      simultaneously, comprehend with clarity the worth of this thing, this life.

PMID- 29019800
TI  - Academic Medical Support to the Ebola Virus Disease Outbreak in Liberia.
AB  - During the Ebola Virus Disease (EVD) epidemic in West Africa (2014-2016), many
      faculty, staff, and trainees from U.S. academic medical centers (i.e., teaching
      hospitals and their affiliated medical schools; AMCs) wished to contribute to the
      response to the outbreak, but many barriers prevented their participation. Here,
      the authors describe a successful long-term academic collaboration in Liberia
      that facilitated participation in the EVD response. This Perspective outlines the
      role the authors played in the response (providing equipment and training,
      supporting the return of medical education), the barriers they faced (logistical
      and financial), and elements that contributed to their success (partnering and
      coordinating their response with both U.S. and African institutions). There is a
      paucity of literature discussing the role of AMCs in disaster response, so the
      authors discuss the lessons learned and offer suggestions about the
      responsibilities that AMCs have and the roles they can play in responding to
      disaster situations.

PMID- 29019801
TI  - Mapping the Landscape, Journeying Together: The Gold Foundation's Model for
      Research-Based Advocacy in Humanism in Medicine.
AB  - Mapping the Landscape, Journeying Together (MTL) is an initiative of the Arnold
      P. Gold Foundation Research Institute. The MTL initiative awards teams with a
      grant to complete a rigorous review of the literature on a topic related to
      humanism in health care. Teams may then seek a discovery or advocacy grant to
      fill in gaps in knowledge or to make or advocate for change. In this Commentary,
      the author reveals the MTL journey through the metaphor of cartography. She
      describes the initial development of a road map, as well as the MTL community's
      experience of navigation, discovery, and exploration. MTL participants are not
      only incrementally adding to a complex body of knowledge but also actively
      cultivating a robust community of practice.

PMID- 29019802
TI  - Design and Evaluation of a Low-Cost Speculum Examination Training Model.
AB  - INTRODUCTION: Learning how to perform a speculum examination is a key component
      of the medical student curriculum, yet there is a paucity of data on the validity
      of available speculum examination models. This purpose of this study is to
      design, evaluate, and improve a low-cost speculum examination model. METHODS: A
      speculum examination training model was created using low-cost or recycled
      materials from other simulators. A total of 54 medical students, residents, and
      faculty in the obstetrics and gynecology department of a single academic
      institution performed speculum examinations on the model. Each participant
      completed a survey to provide qualitative and quantitative data. Using this
      feedback from participants, adjustments were made to the model and a similar
      survey was repeated with a total of 35 medical students and residents. RESULTS:
      The first iteration of the model was viewed positively by most participants.
      Eighty-three percent gave the model either a very realistic or realistic rating.
      Ninety-four percent thought the model was a very useful or useful teaching
      device. There were few significant differences in quantitative data based on
      experience level. Qualitative feedback yielded generally positive remarks with
      areas for improvement. The second iteration of the model was successful in
      differentiating between novice and skilled participants: residents were
      significantly better at identifying cervical position compared with students.
      Eighty-nine percent of participants thought the model was very useful or useful,
      whereas 49% thought the model was very realistic or realistic. DISCUSSION: The
      first iteration of the model demonstrated realism and usefulness; however, it
      lacked construct validity. Participant feedback yielded several helpful
      suggestions to improve the model. The second and final iteration of the model
      differentiated between novice and skilled participants at the cost of realism.
      This low-cost model is a useful tool to aid in teaching the speculum examination.
      Further development and study of the model could lead to a valid tool to evaluate
      speculum examination skills.

PMID- 29019803
TI  - The SPOT GRADE: A New Method for Reproducibly Quantifying Surgical Wound
      Bleeding.
AB  - STUDY DESIGN: Benchtop model with prospective surgeon video testing. OBJECTIVE:
      To create a surface bleeding severity scale, the SPOT GRADE (SG), for
      quantitative assessment of target bleeding site (TBS) blood loss. This is of
      particular interest for spinal surgery due to epidural bleeding and an inability
      to use diathermy and radiofrequency cautery close to nerve roots. SUMMARY OF
      BACKGROUND DATA: A novel apparatus perfusable at known flow rates and simulating
      different sized wounds was used to create movies to educate surgeons on specific
      degrees of bleeding. METHODS: Training (36) and testing (108) videos were created
      using a benchtop apparatus employing different bleeding severities based on the
      six-level SG (none, minimal, mild, moderate, severe, and extreme) and TBS sizes
      (1, 10, and 50 cm). Fourteen surgeons in four specialties (cardiothoracic,
      abdominal, spine, and orthopedic lower extremity) were trained and tested to
      evaluate SG characteristics including inter-rater and intrarater reliability.
      RESULTS: The interclass correlation coefficient was estimated to be 0.89840 (95%
      confidence interval [CI]: 0.85771, 1), whereas the intraclass correlation
      coefficient was estimated to be 0.93673 (95% CI: 0.89603, 1). In 98% of cases
      (95% CI: 0.9736, 0.9927), surgeons correctly identified eligible bleeds for a
      future clinical trial (scores = 1, 2, or 3) and in 91% of cases (95% CI: 0.8895,
      0.9344), surgeons correctly identified noneligible bleeds (scores = 4 or 5). In
      98.6% of cases (95% CI: 0.9777, 0.9945), physicians correctly identified true
      hemostasis (score = 0). Based upon these data the probability of a physician
      rating a bleed incorrectly as hemostasis (score = 0) is estimated to be 1.51%
      (95% CI: 0.0061, 0.0363). CONCLUSION: This SG is reproducible and reliable
      providing a basis for educating surgeons on TBS blood loss. It appears to be a
      new standard for evaluating wound blood loss. LEVEL OF EVIDENCE: 2.

PMID- 29019805
TI  - Do Obese and Extremely Obese Patients Lose Weight After Lumbar Spine Fusions?
      Analysis of a Cohort of 7303 Patients from the Kaiser National Spine Registry.
AB  - : MINI: The outcome of interest was >= 5% weight change 1 year postoperative from
      baseline. Seven thousand three hundred three lumbar fusions in the Kaiser
      Permanente Spine Registry between 2009 and 2013 were analyzed. Weight loss
      occurred in: body mass index < 30, 11.1%; obese, BMI 30 to 39, 16.6%, odds ratio
      = 1.42; extremely obese, body mass index >=40, 21.1%, odds ratio = 1.73. STUDY
      DESIGN: A retrospective cohort study from the Kaiser Permanente Spine Registry.
      OBJECTIVE: The aim of this study was to determine whether obese and extremely
      obese patients with lumbar spine fusions lost a clinically significant amount of
      weight (>=5%) 1 year after their surgery. SUMMARY OF BACKGROUND DATA: Obesity in
      the United States has a prevalence of 35% and is a global health issue. Obesity
      is associated with lumbar spine disease. There is limited evidence regarding
      postsurgical weight loss after spine surgery. METHODS: Adult patients in the
      Kaiser Permanente Spine Registry with lumbar fusions performed between 2009 and
      2013 were included in the study sample (n = 7303). The outcome of interest was
      >=5% weight change 1 year postoperative from baseline. Three body mass index
      (BMI) groups were analyzed (BMI < 30; 30-39 obese; >=40 extremely obese).
      Covariate analysis, multivariable logistic regression, odds ratios (ORs), and 95%
      confidence intervals (95% CIs) are provided. RESULTS: At the time of spine
      surgery, 4456 (61%) had a BMI < 30, 2519 (34.5%) had a BMI between 30 and 39, 232
      (3.2%) had a BMI >=40, and 96 (1.3%) were missing their intraoperative BMI. We
      observed the following weight loss pattern: BMI < 30, 11.1%; BMI 30 to 39, 16.6%;
      BMI >=40, 21.1%. We observed the following weight gain pattern: BMI < 30, 15.6%;
      BMI 30 to 39, 12.7%; BMI >=40, 9.5%. After risk-adjustment, obese and extremely
      obese patients were more likely to lose a clinically significant amount of weight
      1 year after surgery (BMI 30-39: OR = 1.42, 95% CI 1.22-1.65; BMI >=40: OR =
      1.73, 95% CI 1.21-2.47) compared with nonobese patients. CONCLUSION: In this
      large cohort of patients with lumbar spinal fusions, we observed more significant
      weight loss in obese and extremely obese patients than nonobese patients.
      Additional research is needed to determine whether this weight loss is due to
      improvements in back pain and increased physical activity. LEVEL OF EVIDENCE: 3.

PMID- 29019806
TI  - Lumbar Vertebral Endplate Defects on Magnetic Resonance Images: Classification,
      Distribution Patterns, and Associations with Modic Changes and Disc Degeneration.
AB  - STUDY DESIGN: A cross-sectional magnetic resonance (MR) imaging study. OBJECTIVE:
      To classify and characterize endplate defects using routine lumbar MR images and
      to determine associations of endplate defects with Modic changes (MCs) and disc
      degeneration. SUMMARY OF BACKGROUND DATA: Previously, a cadaveric study revealed
      that endplate lesions were common and associated with back pain history. New in
      vivo approaches appropriate for clinical studies are needed to further this
      potentially important line of research on the clinical significance of endplate
      lesions, including their relation with MCs, disc degeneration, and back pain.
      METHODS: Using a MRI archive, 1564 endplates of 133 subjects (59 men and 74
      women, mean age 58.9 +/- 11.9 years) with the presence of MCs were
      retrospectively collected from April of 2014 to June of 2015. On the basis of
      morphological characteristics, a protocol was proposed to identify three distinct
      types of endplate defects, including focal, corner, and erosive defects. The
      location, size, and distribution patterns of various endplate lesions were
      characterized. MCs and disc degeneration were measured to examine their
      associations with endplate defects. RESULTS: Endplate defects were observed in
      27.8% of endplates studied. Greater age was associated with the presence of
      endplate defects. Focal defects were the most common (13.5%), followed by erosive
      defects (11.1%) and corner defects (3.2%). Defect types also differed in size and
      distribution patterns. Endplate defects and MCs had similar distribution patterns
      in the lumbar spine. The presence of endplate defects were associated with the
      presence of MCs (odds ratio = 4.29, P < 0.001), and associated with less disc
      signal intensity and disc height, and greater disc bulging (P < 0.05).
      CONCLUSION: The three endplate defects identified on routine MR images appear to
      represent different pathologies and may play a key role in the pathogenesis of
      MCs. This classification system may facilitate clinical studies on endplate
      defects. LEVEL OF EVIDENCE: 4.

PMID- 29019804
TI  - Quantification of Propionic Acid in the Bovine Spinal Disk After Infection of the
      Tissue With Propionibacteria acnes Bacteria.
AB  - STUDY DESIGN: Research. OBJECTIVE: The goal of this study was to investigate
      whether Propionibacteria acnes infection of the intervertebral disc can be
      detected noninvasively by nuclear magnetic resonance (NMR) spectroscopy. SUMMARY
      OF BACKGROUND DATA: Microbiological studies of surgical samples suggest that a
      significant subpopulation of back pain patients may have occult disc infection
      with P. acnes bacteria. This hypothesis is further supported by a double-blind
      clinical trial showing that back pain patients with Modic type 1 changes may
      respond to antibiotic treatment. Because significant side effects are associated
      with antibiotic treatment, there is a need for a noninvasive method to detect
      whether specific discs in back pain patients are infected with P acnes bacteria.
      METHODS: P. acnes bacteria were obtained from human patients. NMR detection of a
      propionic acid (PA) in the bacteria extracts was conducted on 500 MHz high
      resolution spectrometer, whereas in vivo NMR spectroscopy of an isolated bovine
      disk tissue infected with P. acnes was conducted on 7 T magnetic resonance
      imaging scanner. RESULTS: NMR spectra of P. acnes metabolites revealed a distinct
      NMR signal with identical chemical shits (1.05 and 2.18 ppm) as PA (a primary P.
      acne metabolite). The 1.05 ppm signal does not overlap with other bacteria
      metabolites, and its intensity increases linearly with P. acnes concentration.
      Bovine disks injected with P. acnes bacteria revealed a very distinct NMR signal
      at 1.05 ppm, which linearly increased with P. acnes concentration. CONCLUSION:
      The 1.05 ppm NMR signal from PA can be used as a marker of P. acnes infection of
      discs. This signal does not overlap with other disc metabolites and linearly
      depends on P. acnes concentration. Consequently, NMR spectroscopy may provide a
      noninvasive method to detect disc infection in the clinical setting. LEVEL OF
      EVIDENCE: N/A.

PMID- 29019808
TI  - Commentary on Manuscript 155547R1.

PMID- 29019807
TI  - Pedicle Screw Insertion Accuracy Using O-Arm, Robotic Guidance, or Freehand
      Technique: A Comparative Study.
AB  - STUDY DESIGN: A retrospective radiological study. OBJECTIVE: The aim of this
      study was to evaluate the accuracy of pedicle screw insertion using O-Arm
      navigation, robotic assistance, or a freehand fluoroscopic technique. SUMMARY OF
      BACKGROUND DATA: Pedicle screw insertion using either "O-Arm" navigation or
      robotic devices is gaining popularity. Although several studies are available
      evaluating each of those techniques separately, no direct comparison has been
      attempted. METHODS: Eighty-four patients undergoing implantation of 569 lumbar
      and thoracic screws were divided into three groups. Eleven patients (64 screws)
      had screws inserted using robotic assistance, 25 patients (191 screws) using the
      O-arm, while 48 patients (314 screws) had screws inserted using lateral
      fluoroscopy in a freehand technique. A single experienced spine surgeon assisted
      by a spinal fellow performed all procedures. Screw placement accuracy was
      assessed by two independent observers on postoperative computed tomography (CTs)
      according to the A to D Rampersaud criteria. RESULTS: No statistically
      significant difference was noted between the three groups. About 70.4% of screws
      in the freehand group, 69.6% in the O arm group, and 78.8% in the robotic group
      were placed completely within the pedicle margins (grade A) (P > 0.05). About
      6.4% of screws were considered misplaced (grades C&D) in the freehand group, 4.2%
      in the O-arm group, and 4.7% in the robotic group (P > 0.05). The spinal fellow
      inserted screws with the same accuracy as the senior surgeon (P > 0.05).
      CONCLUSION: The advent of new technologies does not appear to alter accuracy of
      screw placement in our setting. Under supervision, spinal fellows might perform
      equally well to experienced surgeons using new tools. The lack of difference in
      accuracy does not imply that the above-mentioned techniques have no added
      advantages. Other issues, such as surgeon/patient radiation, fiddle factor,
      teaching suitability, etc., outside the scope of our present study, need further
      assessment. LEVEL OF EVIDENCE: 3.

PMID- 29019809
TI  - Atrial Fibrillation and Central Nervous Complications in Liver Transplanted
      Hereditary Transthyretin Amyloidosis Patients.
AB  - BACKGROUND: Central nervous system (CNS) complications are increasingly noted in
      liver transplanted (LTx) hereditary transthyretin amyloid (ATTRm) amyloidosis
      patients; this suggests that the increased survival allows for intracranial ATTRm
      formation from brain synthesized mutant TTR. However, atrial fibrillation (AF), a
      recognised risk factor for ischemic CNS complications, is also observed after
      LTx. The aim of the study was to investigate the occurrence of CNS complications
      and AF in LTx ATTRm amyloidosis patients. METHODS: The medical records of all LTx
      ATTRm amyloidosis patients in the county of Vasterbotten, Sweden, were
      investigated for information on CNS complications, AF, anticoagulation (AC)
      therapy, hypertension, cardiac ischemic disease, hypertrophy, and neurological
      status. RESULTS: Sixty-three patients that had survived for 3 years or longer
      after LTx were included in the analysis. Twenty-five patients had developed 1 or
      more CNS complications at a median of 21 years after onset of disease. AF was
      noted in 21 patients (median time to diagnosis 24 years). Cerebrovascular events
      (CVE) developed in 17 (median time to event 21 years). CVEs occurred
      significantly more often in patients with AF (P < 0.002). AC therapy
      significantly reduced CVEs, including bleeding in patients with AF (P = 0.04).
      Multivariate analysis identified AF as the only remaining regressor with a
      significant impact on CVE (hazard ratio, 3.8; 95% confidence interval 1.1-9.5; P
      = 0.029). CONCLUSIONS: AF is an important risk factor for CVE in LTx ATTRm
      amyloidosis patients, and AC therapy should be considered. However, the increased
      bleeding risk with AC therapy in patients with intracranial amyloidosis should be
      acknowledged.

PMID- 29019810
TI  - Management of Patients Who Receive an Organ Transplant Abroad and Return Home for
      Follow-up Care: Recommendations From the Declaration of Istanbul Custodian Group.
AB  - Eradicating transplant tourism depends on complex solutions that include efforts
      to progress towards self-sufficiency in transplantation. Meanwhile, professionals
      and authorities are faced with medical, legal, and ethical problems raised by
      patients who return home after receiving an organ transplant abroad, particularly
      when the organ has been obtained through illegitimate means. In 2016, the
      Declaration of Istanbul Custodian Group convened an international,
      multidisciplinary workshop in Madrid, Spain, to address these challenges and
      provide recommendations for the management of these patients, which are presented
      in this paper. The core recommendations are grounded in the belief that
      principles of transparency, traceability, and continuity of care applied to
      patients who receive an organ domestically should also apply to patients who
      receive an organ abroad. Governments and professionals are urged to ensure that,
      upon return, patients are promptly referred to a transplant center for evaluation
      and care, not cover the costs of transplants resulting from organ or human
      trafficking, register standardized information at official registries on patients
      who travel for transplantation, promote international exchange of data for
      traceability, and develop a framework for the notification of identified or
      suspected cases of transnational transplant-related crimes by health
      professionals to law enforcement agencies.

PMID- 29019811
TI  - Rhesus Alloimunization Occurs After Rh Incompatible Liver Transplantation in
      Children.

PMID- 29019812
TI  - Venous Thromboembolism After Adult Lung Transplantation: A Frequent Event
      Associated With Lower Survival.
AB  - BACKGROUND: The incidence of venous thromboembolism (VTE) after lung
      transplantation (LTX) varies significantly across studies. Two studies have
      suggested that these thrombotic events are associated with a lower posttransplant
      survival. Herein, we sought to determine the incidence, predictors, and impact of
      VTE on survival after LTX at a quaternary referral center. METHODS: This was a
      large cohort study of LTX recipients. Key outcome parameters were time to VTE
      after transplant and survival. Deep vein thrombosis (DVT) diagnosis required a
      positive ultrasound. Pulmonary embolism diagnosis required either a positive
      chest computed tomography angiogram or a high-probability ventilation/perfusion
      scan. RESULTS: The overall incidence of VTE among 701 LTX recipients was 43.8%,
      of which 97.7% were DVT episodes, of which 71.3% were in the upper extremities.
      Predictors of VTE were prior history of DVT (hazard ratio [HR], 2.82; 95%
      confidence interval [CI], 1.49-5.37), days in intensive care (HR, 1.01; 95% CI,
      1.01-1.02), and the use of extracorporeal membrane oxygenation (HR, 2.22; 95% CI,
      1.43-3.45). Importantly, VTE predicted a lower posttransplant survival (HR, 1.70;
      95% CI, 1.28-2.26), when occurring within or after the first 30 days. The
      location of the DVT, either upper extremity or below the knee, also predicted a
      poor survival. CONCLUSIONS: VTE was frequent in LTX recipients and predicted a
      poor survival even when located in the upper extremities or below the knee. These
      data suggest that aggressive VTE screening/treatment protocols be implemented in
      post-LTX population.

PMID- 29019813
TI  - Contemporary Policies Regarding Alcohol and Marijuana Use Among Liver Transplant
      Programs in the United States.
AB  - BACKGROUND: Alcoholic liver disease is a common indication for orthotopic liver
      transplantation (OLT). Although OLT has been shown to confer survival benefit to
      patients with acute alcoholic hepatitis (AAH), historically most programs require
      a 6-month abstinence period before OLT which excludes patients with AAH.
      Marijuana has become legal in more than half the states in the United States.
      This survey of liver transplant programs was conducted to evaluate current
      policies regarding alcohol, marijuana and methadone use. METHODS: A questionnaire
      was distributed to 100 United Network for Organ Sharing-approved liver transplant
      programs in North America that have performed at least 30 liver transplants/year
      in the last 5 years. RESULTS: Forty-nine programs responded. Only 43% of the
      programs required a specific period of abstinence before transplant for alcoholic
      liver disease and only 26% enforced 6-month abstinence policy. For patients with
      AAH, 71% programs waived the 6-month abstinence requirement and considered
      psychosocial factors, such as family support, patient's motivation, or commitment
      to rehabilitate. Few programs used validated instruments to assess risk of
      relapse in AAH patients. Fourteen percent of programs transplant patients
      actively using marijuana and an additional 28% of programs listed patients using
      marijuana provided they discontinue by the time of OLT. Active methadone users
      were accepted in 45% of the programs. CONCLUSIONS: Policies regarding alcohol use
      have become more flexible particularly toward patients with AAH. Marijuana use is
      also more accepted. Although policies regarding alcohol and marijuana have
      changed significantly in the last decade, they remain highly variable among
      programs.

PMID- 29019815
TI  - An International, Multicenter, Observational Study of Cerebral Oxygenation during
      Infant and Neonatal Anesthesia.
AB  - BACKGROUND: General anesthesia during infancy is associated with neurocognitive
      abnormalities. Potential mechanisms include anesthetic neurotoxicity, surgical
      disease, and cerebral hypoxia-ischemia. This study aimed to determine the
      incidence of low cerebral oxygenation and associated factors during general
      anesthesia in infants. METHODS: This multicenter study enrolled 453 infants aged
      less than 6 months having general anesthesia for 30 min or more. Regional
      cerebral oxygenation was measured by near-infrared spectroscopy. We defined
      events (more than 3 min) for low cerebral oxygenation as mild (60 to 69% or 11 to
      20% below baseline), moderate (50 to 59% or 21 to 30% below baseline), or severe
      (less than 50% or more than 30% below baseline); for low mean arterial pressure
      as mild (36 to 45 mmHg), moderate (26 to 35 mmHg), or severe (less than 25 mmHg);
      and low pulse oximetry saturation as mild (80 to 89%), moderate (70 to 79%), or
      severe (less than 70%). RESULTS: The incidences of mild, moderate, and severe low
      cerebral oxygenation were 43%, 11%, and 2%, respectively; mild, moderate, and
      severe low mean arterial pressure were 62%, 36%, and 13%, respectively; and mild,
      moderate, and severe low arterial saturation were 15%, 4%, and 2%, respectively.
      Severe low oxygen saturation measured by pulse oximetry was associated with mild
      and moderate cerebral desaturation; American Society of Anesthesiology Physical
      Status III or IV versus I was associated with moderate cerebral desaturation.
      Severe low cerebral saturation events were too infrequent to analyze.
      CONCLUSIONS: Mild and moderate low cerebral saturation occurred frequently,
      whereas severe low cerebral saturation was uncommon. Low mean arterial pressure
      was common and not well associated with low cerebral saturation. Unrecognized
      severe desaturation lasting 3 min or longer in infants seems unlikely to explain
      the subsequent development of neurocognitive abnormalities.

PMID- 29019814
TI  - The Optimization of the Prevascularization Procedures for Improving Subcutaneous
      Islet Engraftment.
AB  - BACKGROUND: Subcutaneous islet transplantation is associated with minimal
      invasiveness, but poor vascularization. Thus, the optimization of the
      prevascularization procedures is crucial for improving the outcomes. Although the
      effectiveness of basic fibroblast growth factor (bFGF) was reported, the optimal
      procedures remain unclear. We sought to optimize the prevascularization
      procedures including the use of a novel scaffold, recombinant peptide (RCP).
      METHODS: Devices containing various amount of bFGF with/without heparin or RCP
      were implanted into the subcutaneous space of diabetic C57BL/6 mice. Syngeneic
      islets were transplanted into the prevascularized space. Blood glucose,
      intraperitoneal glucose tolerance, and immunohistochemistry were evaluated.
      RESULTS: The cure rates in all the device groups irrespective of bFGF doses were
      considerably higher than in the nondevice group. The cure rate in the bFGF0 group
      was unexpectedly higher than that in the subcutaneous islet transplant alone
      group (the None group) (57.1% vs 28.6%). Glucose tolerance was ameliorated in the
      bFGF10(-), 10(+) and 15(-) groups. The number of von Willebrand factor-positive
      vessels in the bFGF10(+) group was significantly higher than that in the None and
      bFGF0 groups (P < 0.01). Taken together, the bFGF10(+) group was considered to
      have received optimized procedures. In a marginal graft model, the efficiency in
      the RCP group was better than that in the bFGF10(+) group, furthermore,
      comparable to that in the intraportal transplantation group. Unlike bFGF, no
      bleeding and effusion were observed in the RCP group. CONCLUSIONS: These results
      suggest that optimizing biomaterials to induce efficient prevascularization could
      be a novel strategy for improving subcutaneous islet transplantation.

PMID- 29019816
TI  - Implementation and Evaluation of the Z-Score System for Normalizing Residency
      Evaluations.
AB  - BACKGROUND: Assessment of clinical competence is essential for residency programs
      and should be guided by valid, reliable measurements. We implemented Baker's Z
      score system, which produces measures of traditional core competency assessments
      and clinical performance summative scores. Our goal was to validate use of
      summative scores and estimate the number of evaluations needed for reliable
      measures. METHODS: We performed generalizability studies to estimate the variance
      components of raw and Z-transformed absolute and peer-relative scores and
      decision studies to estimate the evaluations needed to produce at least 90%
      reliable measures for classification and for high-stakes decisions. A subset of
      evaluations was selected representing residents who were evaluated frequently by
      faculty who provided the majority of evaluations. Variance components were
      estimated using ANOVA. RESULTS: Principal component extraction from 8,754
      complete evaluations demonstrated that a single factor explained 91 and 85% of
      variance for absolute and peer-relative scores, respectively. In total, 1,200
      evaluations were selected for generalizability and decision studies. The major
      variance component for all scores was resident interaction with measurement
      occasions. Variance due to the resident component was strongest with raw scores,
      where 30 evaluation occasions produced 90% reliable measurements with absolute
      scores and 58 for peer-relative scores. For Z-transformed scores, 57 evaluation
      occasions produced 90% reliable measurements with absolute scores and 55 for peer
      relative scores. The results were similar for high-stakes decisions. CONCLUSIONS:
      The Baker system produced moderately reliable measures at our institution,
      suggesting that it may be generalizable to other training programs. Raw absolute
      scores required few assessment occasions to achieve 90% reliable measurements.

PMID- 29019817
TI  - Early-Claim Modifiable Factors Associated With Return-to-Work Self-Efficacy Among
      Workers Injured at Work: Are There Differences Between Psychological and
      Musculoskeletal Injuries?
AB  - OBJECTIVE: The objective of this study was to investigate modifiable early-injury
      factors which are associated with self-efficacy to return-to-work (RTW-SE) and
      explore whether these factors are different for people with psychological or
      upper-body musculoskeletal (UB-MSK) injuries. METHODS: The study used a sample of
      workers with a UB-MSK (N = 244) or psychological (N = 113) injury who were off
      work. Differences between injury types were investigated across variables related
      to: (1) communication with RTW stakeholders; and (2) components of the job
      itself. A stratified and multigroup analysis was conducted using structural
      equation modeling (SEM). RESULTS: Injury-stratified models revealed no
      significant differences. In a combined model, higher job autonomy and low-stress
      contact from the RTW coordinator remained significantly associated with higher
      RTW-SE. CONCLUSIONS: Job autonomy and low-stress contact from the RTW coordinator
      are possible areas to target to increase self-efficacy among injured workers.

PMID- 29019818
TI  - I Pledge.

PMID- 29019819
TI  - A Research of Pyogenic Granuloma Genesis Factor With Immunohistochemical
      Analysis.
AB  - Pyogenic granuloma (PG) is a type of vascular tumor for which the growth
      mechanism is poorly understood. Estrogen and progesterone may influence vascular
      malformations by increasing neovascularization in the lesions. Pregnancy tumor is
      a term for PG that occurs on the gingival mucosa of pregnant women in response to
      local irritation or injury. The etiology and pathogenesis of this phenomenon are
      not fully understood. Hormonal imbalance has been hypothesized to be responsible
      for the development of gingival hyper-reactive inflammatory responses. Moreover,
      it has been shown in vitro that the female sex hormone is a potential regulator
      of the production of several growth factors, such as vascular endothelial growth
      factor (VEGF), basic fibroblast growth factor, and nerve growth factor, in
      various cell types. Epidermal growth factor receptor (EGFR) is also involved in a
      signaling cascade that influences proliferation and other tumor-promoting
      activities, as well as the responsiveness to chemotherapy. The aim of this study
      was to examine the relationship between PG pathogenesis and hormone imbalance in
      21 patients. All specimens were analyzed by immunohistochemical staining with
      hematoxylin and eosin for the following hormones: estrogen receptor, progesterone
      receptor, VEGF, and EGFR. The analysis of the specimens showed that estrogen
      receptor and EGFR were not associated with PG, while VEGF was statistically
      related to PG. In addition, there was no significantly difference between sex,
      tumor location, or pregnancy. There are few studies about correlation between the
      pathogenesis of PG and sex hormones or growth factors demonstrated via
      immunohistochemical analysis. The results of this study indicate that estrogen
      and progesterone do not influence the pathogenesis of PG; however, VEGF may be
      associated with the pathogenesis of PG.

PMID- 29019820
TI  - Split-Overlapping Genioplasty: Surgical Technique, Morphological and Radiological
      Long-Term Outcomes.
AB  - BACKGROUND: The overlapping bone flap genioplasty, described by Tessier, was
      developed to treat major retrognathia or long and retruded chins. For 15 years,
      we have used a modified version of this technique to avoid its drawbacks. The aim
      of this article is to describe our modification and evaluate the long-term
      morphologic and radiologic outcomes. PATIENTS AND METHOD: The authors included
      every split-overlapping genioplasty performed in our department between 2004 and
      2014. Demographics, surgical data, and complications were recorded. Radiologic
      bone resorption was evaluated comparing preoperative, day-1 postoperative, and
      year-1 postoperative cephalometric x-rays. Morphologic outcomes were evaluated on
      standardized pre- and postoperative views using an analogic Likert scale.
      SURGICAL TECHNIQUE: The main modification of the procedure consists in separating
      the posterior cortex of the transplant using a reciprocating saw. After
      overlapping the reduced transplant onto the mandible, the posterior cortex is
      used as an apposition graft to soften the labiomental crease. RESULTS: Forty
      seven patients were analyzed during this period. In 44 patients, the procedure
      was combined with mandibular and/or maxillary osteotomy. The average reduction of
      symphysis height was 5 mm, and the average pogonion advancement was 4.3 mm. After
      1 year, we recorded 7% average bone resorption. No major complications (nerve
      injury, hematoma, among others) were reported. Morphologic outcomes were deemed
      satisfactory or very satisfactory in the vast majority of cases. CONCLUSION:
      Split-overlapping genioplasty is a safe and reliable procedure with stable, long
      lasting outcomes. This versatile technique is particularly useful for the
      correction of a massive symphysis or high and retruded chins.

PMID- 29019821
TI  - From the Editor.

PMID- 29019822
TI  - Endocervical Polyp With Florid "Epidermal Metaplasia": Report of a Previously
      Undescribed Phenomenon From a Dermatopathologic View: Is it an Epidermal
      Inclusion Cyst or a Dermoid Cyst.

PMID- 29019824
TI  - Risk of vertebral compression fractures in multiple myeloma patients: A finite
      element study: Erratum.

PMID- 29019825
TI  - Retrospective study of intravascular large B-cell lymphoma cases diagnosed in
      Quebec: A retrospective study of 29 case reports: Erratum.

PMID- 29019823
TI  - From Classical to Unusual: Report on 5 Cases of Transient Reactive Aquagenic
      Pseudokeratoderma and Review of the Literature.
AB  - Transient reactive aquagenic pseudokeratoderma is characterized by transient
      whitish and translucent papules after water exposure in palms and soles. We
      report 5 additional cases and their histopathologic features. Patient 5 showed a
      topography that had not been reported before; this demonstrates that it is not an
      exclusive condition of palms and soles. Patient 2 presents very subtle clinical
      findings, making difficult the diagnosis. And the other 3 patients have a typical
      presentation. Transient reactive aquagenic pseudokeratoderma has heterogeneous
      clinical features; in some cases, histopathologic findings, although subtle, help
      to confirm the diagnosis.

PMID- 29019826
TI  - Thanks for being there.

PMID- 29019827
TI  - LETTERS.

PMID- 29019828
TI  - LEGAL QUESTIONS.

PMID- 29019830
TI  - Breaking the link between I.V. therapy and HIT.

PMID- 29019834
TI  - ...About multiple endocrine neoplasia type 1.

PMID- 29019832
TI  - Treating pain after a total joint replacement.

PMID- 29019837
TI  - Best-Practice Interventions: Suppressing the scourge of AMI.

PMID- 29019836
TI  - Best-Practice Interventions: Suppressing the scourge of AMI.

PMID- 29019838
TI  - Heart attack.

PMID- 29019839
TI  - Understanding the new AHA guidelines part II.

PMID- 29019840
TI  - Nursing2006 Patient-safety survey report.

PMID- 29019841
TI  - Nursing2006 Patient-safety survey report.

PMID- 29019842
TI  - Managing pseudoaneurysm after cardiac catheterization.

PMID- 29019843
TI  - Questioning judgment.

PMID- 29019844
TI  - CCRN review: Test yourself with this practice exam.

PMID- 29019845
TI  - Help your patient combat postoperative atelectasis.

PMID- 29019846
TI  - Calling to say good-bye.

PMID- 29019847
TI  - INSIGHTS ON DEATH & DYING.

PMID- 29019848
TI  - Combination drugs...

PMID- 29019850
TI  - Ventriculo-Arterial Coupling Analysis Predicts the Hemodynamic Response to
      Norepinephrine in Hypotensive Postoperative Patients: A Prospective Observational
      Study.
AB  - OBJECTIVES: The objectives of the present study were to evaluate, in patients
      with persistent arterial hypotension in the immediate postcardiac surgery period,
      the effects of norepinephrine infusion on ventriculo-arterial coupling, its
      determinants: arterial elastance and end-systolic ventricular elastance, and to
      test the ability of arterial elastance to end-systolic ventricular elastance
      ratio to predict stroke volume increases. DESIGN: Prospective observational
      study. SETTING: Cardiac-vascular surgical ICU. PATIENTS: Twenty-eight
      postoperative cardiac surgery patients, in whom physicians decided to administer
      norepinephrine infusion, were included. MEASUREMENTS AND MAIN RESULTS: Arterial
      pressure, stroke volume index, cardiac index, indexed total peripheral
      resistance, arterial compliance, arterial elastance, and end-systolic ventricular
      elastance, were measured before and after norepinephrine infusion. We estimated
      ventriculo-arterial coupling by the arterial elastance to end-systolic
      ventricular elastance ratio and defined stroke volume responders by a stroke
      volume increase greater than or equal to 15%. Twenty-two of the 28 subjects had
      altered ventriculo-arterial coupling (1.87 [1.57-2.51] vs 1.1 [1-1.18]). Fifteen
      of the 28 subjects (54%) were stroke volume responders. At baseline, stroke
      volume responders had similar arterial pressure, higher indexed total peripheral
      resistance, arterial elastance, arterial elastance to end-systolic ventricular
      elastance ratio (2.21 [1.69-2.89] vs 1.33 [1.1-1.56]; p < 0.05), and lower
      arterial compliance, indexed total peripheral resistance and cardiac index.
      Norepinephrine significantly increased arterial pressure in all subjects. In
      stroke volume responders, norepinephrine increased arterial elastance, end
      systolic ventricular elastance, cardiac index, and improved arterial
      elastance/end-systolic ventricular elastance coupling. The baseline arterial
      elastance to end-systolic ventricular elastance ratio predicted stroke volume
      responsiveness (area under the curve [95% CI], 0.87 [0.71-1]; p < 0.0001).
      CONCLUSIONS: In patients with arterial hypotension norepinephrine increased end
      systolic ventricular elastance and arterial elastance. The effects of
      norepinephrine on stroke volume depend on baseline ventriculo-arterial coupling.
      Although norepinephrine infusion corrects arterial hypotension in all subjects,
      increase of stroke volume occurred only in subjects with altered ventriculo
      arterial coupling.

PMID- 29019853
TI  - Holder-Pasteurized Human Donor Milk: How Long Can It Be Preserved?
AB  - OBJECTIVE: When own mother's milk falls short, pasteurized human donor milk is
      recommended as alternative feeding for preterm infants. Donor milk has to meet
      the highest safety standards, but its processing and storage is expensive. The
      recommended storage time of pasteurized donor milk is 3 months. The objective of
      the present study was to determine whether the frozen storage time of pasteurized
      donor milk can be extended beyond 3 months without compromising its safety and
      quality. METHODS: For this prospective observational study breast milk samples of
      34 unique women, collected between November 2014 and June 2015, were provided by
      the Dutch Human Milk Bank. Samples were Holder pasteurized within 3 months after
      expression and stored at -20 degrees C. Analysis of both bacterial growth (by
      inoculation of milk on a blood and a cysteine-, lactose-, and electrolyte
      deficient agar) and fat, crude protein, carbohydrate and energy content of milk
      (analyzed by infrared spectroscopy) was done monthly during the first 6 months
      and every 2 months thereafter, up to 1 year postpasteurization. RESULTS: Thirty
      of 306 (9.8%) follow-up samples showed bacterial growth when cultured. None of
      the samples showed sequential contamination with the same strain up to 8 months
      of frozen storage. No significant decreases in macronutrients and energy content
      were observed over 8 months. CONCLUSION: Pasteurized human donor milk can be
      stored safely for 8 months at -20 degrees C, without compromising its
      macronutrient and energy content. This longer storage time will reduce disposal
      of expired donor milk and subsequently reduce costs.

PMID- 29019852
TI  - Modification of Tracheal Cuff Shape and Continuous Cuff Pressure Control to
      Prevent Microaspiration in an Ex Vivo Pig Tracheal Two-Lung Model.
AB  - OBJECTIVES: Microaspiration of subglottic secretions plays a pivotal role in
      ventilator-associated pneumonia. Impact of endotracheal tube cuff material and
      shape on tracheal sealing performance remains debated. The primary objective was
      to compare the tracheal sealing performance of polyvinyl chloride tapered,
      cylindrical and spherical cuffs. Secondary objectives were to determine the
      impact of continuous cuff pressure control on sealing performance and pressure
      variability. DESIGN: Prospective randomized ex vivo animal study. SETTING: French
      research laboratory. SUBJECTS: Seventy-two ex vivo pig tracheal two-lung blocks.
      INTERVENTIONS: Blocks were randomly intubated with cylindrical (n = 26), tapered
      (n = 24), or spherical (n = 22) polyvinyl chloride endotracheal tube cuffs. Two
      milliliter of methylene blue were instilled above the cuff to quantify
      microaspirations, and lungs were ventilated for 2 hours. Continuous cuff pressure
      control was implemented in 33 blocks. MEASUREMENTS AND MAIN RESULTS: Cuff
      pressures were continuously recorded, and after 2 hours, a microaspiration score
      was calculated. Tapered cuffs improved cuff sealing performance compared with
      spherical cuffs with or without continuous cuff pressure control. Compared with
      spherical cuffs, tapered cuffs reduced the microaspiration score without and with
      continuous pressure control by 65% and 72%, respectively. Continuous cuff
      pressure control did not impact sealing performance. Tapered cuffs generated
      higher cuff pressures and increased the time spent with overinflation compared
      with spherical cuffs (median [interquartile range], 77.9% [0-99.8] vs. 0% [0
      0.5]; p = 0.03). Continuous cuff pressure control reduced the variability of
      tapered and spherical cuffs likewise the time spent with overinflation of tapered
      and cylindrical cuffs. CONCLUSIONS: Polyvinyl chloride tapered cuffs sealing
      enhanced performance at the cost of an increase in cuff pressure and in time
      spent with overinflation. Continuous cuff pressure control reduced the
      variability and normalized cuff pressures without impacting sealing performance.

PMID- 29019851
TI  - Outcomes of ICU Patients With a Discharge Diagnosis of Critical Illness
      Polyneuromyopathy: A Propensity-Matched Analysis.
AB  - OBJECTIVES: To assess the impact of a discharge diagnosis of critical illness
      polyneuromyopathy on health-related outcomes in a large cohort of patients
      requiring ICU admission. DESIGN: Retrospective cohort with propensity score
      matched analysis. SETTING: Analysis of a large multihospital database. PATIENTS:
      Adult ICU patients without preexisting neuromuscular abnormalities and a
      discharge diagnosis of critical illness polyneuropathy and/or myopathy along with
      adult ICU propensity-matched control patients. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: Of 3,567 ICU patients with a discharge diagnosis of critical
      illness polyneuropathy and/or myopathy, we matched 3,436 of these patients to
      3,436 ICU patients who did not have a discharge diagnosis of critical illness
      polyneuropathy and/or myopathy. After propensity matching and adjusting for
      unbalanced covariates, we used conditional logistic regression and a repeated
      measures model to compare patient outcomes. Compared to patients without a
      discharge diagnosis of critical illness polyneuropathy and/or myopathy, patients
      with a discharge diagnosis of critical illness polyneuropathy and/or myopathy had
      fewer 28-day hospital-free days (6 [0.1] vs 7.4 [0.1] d; p < 0.0001), had fewer
      28-day ventilator-free days (15.7 [0.2] vs 17.5 [0.2] d; p < 0.0001), had higher
      hospitalization charges (313,508 [4,853] vs 256,288 [4,470] dollars; p < 0.0001),
      and were less likely to be discharged home (15.3% vs 32.8%; p < 0.0001) but had
      lower in-hospital mortality (13.7% vs 18.3%; p < 0.0001). CONCLUSIONS: In a
      propensity-matched analysis of a large national database, a discharge diagnosis
      of critical illness polyneuropathy and/or myopathy is strongly associated with
      deleterious outcomes including fewer hospital-free days, fewer ventilator-free
      days, higher hospital charges, and reduced discharge home but also an
      unexpectedly lower in-hospital mortality. This study demonstrates the clinical
      importance of a discharge diagnosis of critical illness polyneuropathy and/or
      myopathy and the need for effective preventive interventions.

PMID- 29019854
TI  - The Best Choice for Second-line Agent in Standard Treatment-refractory Children
      With Autoimmune Hepatitis.

PMID- 29019855
TI  - Bovine Colostrum for Preterm Infants in the First Days of Life: A Randomized
      Controlled Pilot Trial.
AB  - OBJECTIVES: Mother's own milk (MM) is the best nutrition for newborn preterm
      infants, but is often limited in supply just after birth. Pasteurized human donor
      milk (DM), and especially preterm infant formula (IF) are less optimal diets than
      MM. We hypothesized that it is feasible to use bovine colostrum (BC), the first
      milk from cows, as a supplement to MM, during the first weeks after preterm
      birth. METHODS: In an open-label, randomized, controlled pilot safety trial,
      supplementation of MM with BC was compared with DM supplementation (Danish unit)
      or IF supplementation (Chinese unit). If MM was limited or lacking, BC, DM or IF
      were given according to local feeding guidelines during the first 14 days of
      life. RESULTS: Forty infants were included and randomized in Denmark and in
      China, with gestational ages 29.9 +/- 0.4 and 31.1 +/- 0.2 weeks, respectively.
      Infants supplemented with BC received more enteral protein (P < 0.05) and tended
      to reach full enteral feeding earlier (China only). Eight infants fed BC showed a
      temporary elevation in plasma tyrosine on day 7, versus 2 infants in the DM/IF
      groups. There were no differences between diet groups in feeding intolerance or
      clinical adverse events. CONCLUSIONS: Our results indicate that it is feasible to
      use BC as a supplement to MM during the first weeks of life to increase enteral
      protein intake in preterm infants. Plasma tyrosine levels may be a good marker
      for excessive protein intake. A larger randomized trial is required to test the
      safety and possible short- and long-term clinical benefits of BC supplementation
      during the first weeks of life for preterm infants.

PMID- 29019856
TI  - Cost-utility Analysis: Thiopurines Plus Endoscopy-guided Biological Step-up
      Therapy is the Optimal Management of Postoperative Crohn's Disease.
AB  - BACKGROUND: Postoperative recurrence of Crohn's disease is common. This study
      sought to assess whether the postoperative management should be based on
      biological therapy alone or combined with thiopurines and whether the therapy
      should be started immediately after surgery or guided by either endoscopic or
      clinical recurrence. METHODS: A Markov model was developed to estimate expected
      health outcomes in quality-adjusted life years (QALYs) and costs in Canadian
      dollars (CAD$) accrued by hypothetical patients with high recurrence risk after
      ileocolic resection. Eight strategies of postoperative management were evaluated.
      A lifetime time horizon, an annual discount rate of 5%, a societal perspective,
      and a cost-effectiveness threshold of 50,000 CAD$/QALY were assumed.
      Deterministic and probabilistic sensitivity analyses were conducted. The model
      was validated against randomized trials and historical cohorts. RESULTS: Three
      strategies dominated the others: endoscopy-guided full step-up therapy (14.80
      QALYs, CAD$ 462,180), thiopurines immediately post-surgery plus endoscopy-guided
      biological step-up therapy (14.89 QALYs, CAD$ 464,099) and combination therapy
      immediately post-surgery (14.94 QALYs, CAD$ 483,685). The second strategy was the
      most cost-effective, assuming a cost-effectiveness threshold of 50,000 CAD$/QALY.
      Probabilistic sensitivity analysis showed that the second strategy has the
      highest probability of being the optimal alternative in all comparisons at cost
      effectiveness thresholds from 30,000 to 100,000 CAD$/QALY. The strategies guided
      only by clinical recurrence and those using biologics alone were dominated.
      CONCLUSIONS: According to this decision analysis, thiopurines immediately after
      surgery and addition of biologics guided by endoscopic recurrence is the optimal
      strategy of postoperative management in patients with Crohn's disease with high
      risk of recurrence (see Video Abstract, Supplemental Digital Content 1,
      http://links.lww.com/IBD/B654).

PMID- 29019857
TI  - Interleukin-27 Is a Potential Rescue Therapy for Acute Severe Colitis Through
      Interleukin-10-Dependent, T-Cell-Independent Attenuation of Colonic Mucosal
      Innate Immune Responses.
AB  - BACKGROUND: If treatment with intravenous steroids fail, inflammatory bowel
      disease patients with acute severe colitis face systemic anti-tumor necrosis
      factor biologic rescue therapy or colectomy. Interleukin (IL)-27 is a cytokine
      with an immunosuppressive role in adaptive immune responses. However, the IL-27
      receptor complex is also expressed on innate immune cells, and there is evidence
      that IL-27 can impact the function of innate cell subsets, although this
      particular functionality in vivo is not understood. Our aim was to define the
      efficacy of IL-27 in acute severe colitis and characterize novel IL-27-driven
      mechanisms of immunosuppression in the colonic mucosa. METHODS: We assessed oral
      delivery of Lactococcus lactis expressing an IL-27 hyperkine on the innate immune
      response in vivo in a genetically intact, noninfective, acute murine colitis
      model induced by intrarectal instillation of 2,4,6-trinitrobenzenesulfonic acid
      in SJL/J mice. RESULTS: IL-27 attenuates acute severe colitis through the
      reduction of colonic mucosal neutrophil infiltrate associated with a decreased
      CXC chemokine gradient. This suppression was T cell independent and IL-10
      dependent, initially featuring enhanced mucosal IL-10. IL-27 was associated with
      a reduction in colonic proinflammatory cytokines and induced a multifocal,
      strong, positive nuclear expression of phosphorylated STAT-1 in mucosal
      epithelial cells. CONCLUSION: We have defined novel mechanisms of IL-27
      immunosuppression toward colonic innate immune responses in vivo. Mucosal
      delivery of IL-27 has translational potential as a novel therapeutic for
      inflammatory bowel disease, and it is a future mucosal directed rescue therapy in
      acute severe inflammatory bowel disease.

PMID- 29019859
TI  - Outcomes after Phalloplasty: Do Transgender Patients and Multiple Urethral
      Procedures Carry a Higher Rate of Complication?
AB  - BACKGROUND: Phalloplasty is associated with improved quality-of-life in those
      with penile defects, and in female-to-male transgender (transmale) patients
      seeking gender-confirming surgery. However, aggregate complication and outcome
      data are sparse. This study compares phalloplasty outcomes between transmale and
      cismale patients and between those with primary versus staged urethroplasty.
      METHODS: A comprehensive literature search of PubMed, MEDLINE, and Google Scholar
      databases was conducted for studies relating to phalloplasty. Data on techniques,
      complications, outcomes, and patient demographics were collected. Analysis using
      the random-effects model with subgroup analyses was performed. RESULTS: A total
      of 50 studies (1351 patients) were included: 19 studies (869 patients) for
      transmale patients and 31 studies (482 patients) for cismale patients. The
      urethral complication rate in the transmale group was 39.4 percent (95 percent
      CI, 30.6 to 48.9 percent; p = 0.028) compared to 24.8 percent (95 percent CI,
      16.5 to 35.4 percent; p < 0.001) in the cismale group. The overall flap
      complication rates for transmale and cismale patients were 10.8 percent (95
      percent CI, 7.0 to 16.2 percent; p < 0.001) and 8.1 percent (95 percent CI, 5.5
      to 11.7 percent; p < 0.001), respectively. Twenty-three studies (723 patients)
      used primary urethroplasty and 13 studies (210 patients) performed staged
      urethroplasty procedures. Flap complication rates of primary and staged
      urethroplasty were 8.6 percent (95 percent CI, 5.3 to 13.8 percent; p < 0.001)
      and 16.7 percent (95 percent CI, 10.7 to 24.9 percent; p < 0.001), respectively.
      Primary urethroplasty had superior outcomes of voiding while standing, sexual
      function, and patient satisfaction compared with staged urethroplasty.
      CONCLUSIONS: Cismale patients undergoing phalloplasty had lower urethral and flap
      complication rates compared with transmale patients. Staged urethroplasty had
      more flap complications, and worse outcomes and patient satisfaction compared
      with primary urethroplasty.

PMID- 29019858
TI  - Epicutaneous Tolerance Induction to a Bystander Antigen Abrogates Colitis and
      Ileitis in Mice.
AB  - BACKGROUND: Although inflammatory bowel disease (IBD) is a failure in maintaining
      tolerance to the intestinal microbiota, few studies have investigated the use of
      immunologic tolerance as a treatment approach for IBD. We hypothesized that
      induction of immune tolerance at a distal site could suppress intestinal
      inflammation through a process of bystander regulation. METHODS: Epicutaneous
      tolerance was induced by topical application of ovalbumin (OVA) using a Viaskin
      patch for 48 hours. In some experiments, a single feed of ovalbumin was used to
      drive epicutaneous tolerance-induced regulatory T cells (Tregs) to the intestine.
      The mechanism of tolerance induction was tested using neutralizing antibodies
      against TGF-beta, IL-10, and Treg depletion using Foxp3-DTR mice. The capacity of
      skin-draining Tregs, or epicutaneous tolerance, to prevent or treat experimental
      IBD was tested using T-cell transfer colitis, dextran sodium sulfate (DSS)
      colitis, and ileitis in SAMP-YITFc mice. Weight loss, colonic inflammatory
      cytokines and histology were assessed. RESULTS: Epicutaneous exposure to
      ovalbumin induced systemic immune tolerance by a TGF-beta-dependent, but IL-10
      and iFoxp3 Treg-independent mechanism. Skin draining Tregs suppressed the
      development of colitis. Epicutaneous tolerance to a model antigen prevented
      intestinal inflammation in the dextran sodium sulfate and SAMP-YITFc models and
      importantly could halt disease in mice already experiencing weight loss in the T
      cell transfer model of colitis. This was accompanied by a significant
      accumulation of LAP and Foxp3 Tregs in the colon. CONCLUSIONS: This is the first
      demonstration that epicutaneous tolerance to a model antigen can lead to
      bystander suppression of inflammation and prevention of disease progression in
      preclinical models of IBD.

PMID- 29019860
TI  - The Addition of Platelet-Rich Plasma to Facial Lipofilling: A Double-Blind,
      Placebo-Controlled, Randomized Trial.
AB  - BACKGROUND: Lipofilling is a treatment modality to restore tissue volume, but it
      may also rejuvenate the aging skin. Platelet-rich plasma has been reported to
      augment the efficacy of lipofilling, both on graft take and rejuvenation, by
      altering the adipose-derived stem cells. The authors hypothesized that addition
      of platelet-rich plasma would increase the rejuvenating effect and shorten
      recovery time. METHODS: The study conducted was a single-center, double-blind,
      placebo-controlled, randomized trial (2012 to 2015). In total, a well-defined
      cohort of 32 healthy female patients enrolled in the study, with 25 completing
      the follow-up. All patients underwent aesthetic facial lipofilling with either
      saline or platelet-rich plasma added. Outcome was determined by changes in skin
      elasticity, volumetric changes of the nasolabial fold, recovery time, and patient
      satisfaction during follow-up (1 year). RESULTS: Platelet-rich plasma did not
      improve the outcome of facial lipofilling when looking at skin elasticity
      improvement, graft volume maintenance in the nasolabial fold. Reversal of the
      correlation between age and elasticity, however, might suggest a small effect
      size, and thus might not be significant with our small study population.
      CONCLUSIONS: This randomized, double-blind, placebo-controlled study clearly has
      shown that platelet-rich plasma significantly reduces postoperative recovery time
      but does not improve patient outcome when looking at skin elasticity, improvement
      of the nasolabial fold, or patient satisfaction. The reversal of the correlation
      between age and elasticity might indicate some effect on skin but requires more
      power in future studies. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

PMID- 29019861
TI  - The Lateral Thigh Perforator Flap for Autologous Breast Reconstruction: A
      Prospective Analysis of 138 Flaps.
AB  - BACKGROUND: The septocutaneous tensor fasciae latae or lateral thigh perforator
      flap was previously introduced by the authors' group as an alternative flap for
      autologous breast reconstruction when the abdomen is not suitable as a donor
      site. The authors analyzed their experience with the lateral thigh perforator
      flap and present the surgical refinements that were introduced. METHODS: A
      prospective study was conducted of all lateral thigh perforator flap breast
      reconstructions performed since September of 2012. Patient demographics,
      operative details, complications, and flap reexplorations were recorded.
      Preoperative imaging with magnetic resonance angiography was performed in all
      patients. Surgical refinements introduced during this study included limitation
      of the flap width and the use of quilting sutures at the donor site. RESULTS: A
      total of 138 lateral thigh perforator flap breast reconstructions were performed
      in 86 consecutive patients. Median operative times were 277 minutes (range, 196
      to 561 minutes) for unilateral procedures and 451 minutes (range, 335 to 710
      minutes) for bilateral. Median flap weight was 348 g (range, 175 to 814 g). Two
      total flap losses (1.4 percent) were recorded, and 11 flaps (8.0 percent)
      required reexploration, which resulted in viable flaps. The incidence of donor
      site complications was reduced significantly after the surgical refinements were
      introduced. Wound problems decreased from 40.0 percent to 6.3 percent, seroma
      decreased from 25.0 percent to 9.5 percent, and infection decreased from 27.5
      percent to 9.5 percent. CONCLUSIONS: The lateral thigh perforator flap is an
      excellent option for autologous breast reconstruction, with minimal recipient
      site complications. The surgical refinements resulted in a significant reduction
      of donor-site complications. Therefore, the lateral thigh perforator flap is
      currently the authors' second choice after the deep inferior epigastric artery
      perforator flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 29019863
TI  - Bony/Cartilaginous Mismatch: A Radiologic Investigation into the Cause of Tension
      Nose Deformity.
AB  - BACKGROUND: Tension nose deformity is believed to be caused by an "oversized"
      septal quadrangular cartilage. Prior studies have shown that quadrangular
      cartilage size is relatively consistent in populations. The authors hypothesize
      that the tension nose deformity is actually caused by an external extrusion of a
      normal sized septal cartilage from an undersized bony septal encasement. METHODS:
      A retrospective case-control study of sagittal computed tomographic scans was
      conducted, measuring the perimeter and surface area of the quadrangular cartilage
      and bony septal aperture in tension nose cases and controls. Statistical analysis
      was performed. RESULTS: Of 23 patients enrolled in the study, 12 patients were
      sorted into the tension nose group, and 11 patients were considered controls.
      Both groups had similar perimeter and surface area of their quadrangular
      cartilage, without statistical difference between the two groups. However, the
      tension nose group had a statistically significant reduction in bony septal
      aperture perimeter compared with controls (p < 0.01) and a larger externally
      extruded septum compared with their internal septal size. They also had a
      substantially higher rate of septal deviation than controls. CONCLUSIONS: The
      results of this study suggest that a mismatch between a small bony septal
      aperture and a normal sized septal quadrangular cartilage may be responsible for
      caudal, upper lip, and dorsal fullness seen with the tension nose deformity
      caused by external extrusion of cartilage. Septal deviation may co-occur as a
      buckling phenomenon in a limited bony space. Surgical strategies to match the
      entire quadrangular cartilage size to the bony framework are suggested. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 29019862
TI  - Complications and Patient-Reported Outcomes after Abdominally Based Breast
      Reconstruction: Results of the Mastectomy Reconstruction Outcomes Consortium
      Study.
AB  - BACKGROUND: Abdominal flap reconstruction is the most popular form of autologous
      breast reconstruction. The current study compared complications and patient
      reported outcomes after pedicled transverse rectus abdominis myocutaneous (TRAM),
      free TRAM, deep inferior epigastric perforator (DIEP), and superficial inferior
      epigastric artery (SIEA) flaps. METHODS: Patients undergoing abdominally based
      breast reconstruction at 11 centers were prospectively evaluated for abdominal
      donor-site and breast complications. Patient-reported outcomes were measured by
      the BREAST-Q and Patient-Reported Outcomes Measurement Information System
      surveys. Mixed-effects regression models were used to assess the effects of
      procedure type on outcomes. RESULTS: Seven hundred twenty patients had 1-year
      follow-up and 587 had 2-year follow-up. Two years after reconstruction, SIEA
      compared with DIEP flaps were associated with a higher rate of donor-site
      complications (OR, 2.7; p = 0.001); however, SIEA flaps were associated with
      higher BREAST-Q abdominal physical well-being scores compared with DIEP flaps at
      1 year (mean difference, 4.72, on a scale from 0 to 100; p = 0.053). This
      difference was not significant at 2 years. Abdominal physical well-being scores
      at 2 years postoperatively were lower in the pedicled TRAM flap group by 7.2
      points (p = 0.006) compared with DIEP flaps and by 7.8 points (p = 0.03) compared
      with SIEA flaps, and in the free TRAM flap group, scores were lower by 4.9 points
      (p = 0.04) compared with DIEP flaps. Bilateral reconstruction had significantly
      lower abdominal physical well-being scores compared with unilateral
      reconstruction. CONCLUSIONS: Although all abdominally based flaps are viable
      breast reconstruction options, DIEP and SIEA flaps are associated with higher
      abdominal physical well-being than pedicled and free TRAM flaps. Although SIEA
      flaps offer the advantage of not violating the fascia, higher rates of donor-site
      complications may diminish patient satisfaction. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, II.

PMID- 29019866
TI  - Haemostatic balance in patients with end-stage cirrhosis: low protein C is the
      predominant coagulant protein deficiency.

PMID- 29019865
TI  - How diet can impact gut microbiota to promote or endanger health.
AB  - PURPOSE OF REVIEW: Disturbances of the intestinal microbiota have been
      increasingly implicated in driving various diseases associated with a broad range
      of chronic inflammatory state. Such diseases have increased in incidence since
      the mid-20th century, and have roughly correlated with societal changes in food
      production during this period. RECENT FINDINGS: Considering how changes in diet
      may have impacted gut microbiota and exploring whether targeted modulations of
      diet might be a means of optimizing microbiota composition to promote health.
      SUMMARY: Recent literature demonstrates that modulation of diet has potential to
      both beneficially and detrimentally impact microbiota composition and how it
      interacts with its host. Herein, we discuss recent studies by ourselves and
      others that demonstrate the potential for changes in diet to have profound
      impacts on the gut microbiota in ways that can have beneficial or detrimental
      effects on host health.

PMID- 29019867
TI  - The Effects Of Various Weighted Implements On Baseball Swing Kinematics In
      Collegiate Baseball Players.
AB  - The purpose of this study was to investigate the effects of different warm-up
      (WU) devices on bat swing parameters including maximal resultant velocity (MRV),
      resultant velocity at ball contact (RVBC), time difference between MRV and RVBC,
      bat angle at MRV, bat angle at RVBC, and perceptual differences (PD) of each WU
      implement utilized by National Collegiate Athletic Association (NCAA) Division-I
      baseball players. Fifteen varsity baseball players completed one experimental
      session during fall training. Retro-reflective markers were placed on the bat and
      tee to measure basic bat kinematics during the swing. Participants completed a
      general calisthenics WU before being counter-balanced into one of four WU
      conditions: standard bat (SB) (33in/30oz), fungo (FG) (10.6oz), weighted gloves
      with SB (WG) (55.6oz) and donut with SB (DN) (55.6oz). Each participant was asked
      to perform their normal on deck routine over a two-minute period, finishing with
      5 practice swings with the designated condition. After completion of the WU, a
      one-minute rest period (simulating normal game conditions) was given to allow
      each participant to get set to perform five maximal swings with a SB. Five, 1x4
      (group x condition) repeated measures analysis of variance examined the
      aforementioned variables. There were no significant differences in MRV, RVBC,
      time difference between MRV and RVBC, and bat angle at MRV and RVBC between all
      WU conditions. If presented with the current options, athletes should choose the
      WU implement with which they are most comfortable using prior to an at bat
      situatiossn.

PMID- 29019868
TI  - Vulvar Myxoid Liposarcoma, an Extremely Rare Diagnosis: A Case Report and Review
      of Literature.
AB  - Malignant lipomatous tumors of the vulva are an extremely rare entity. We report
      the case of a 53-year-old patient with a nodule on her right labium majus whose
      histological and immunohistochemical profile (S100 and p16) confirmed a diagnosis
      of vulvar myxoid liposarcoma.

PMID- 29019869
TI  - The Analysis of Cell Cycle-related Proteins in Ovarian Clear Cell Carcinoma
      Versus High-grade Serous Carcinoma.
AB  - In Japan, the frequency of ovarian clear cell carcinoma (CCC) is twice as high as
      that in the United States and Europe. Often, patient prognosis with CCC is poor
      because of chemoresistance. Here, we focus on the cell cycle, which is one of the
      mechanisms of chemoresistance. To detect the informative markers and improve the
      strategy of chemotherapy for CCC, we performed immunohistochemical staining of
      cell cycle-related proteins in ovarian malignant tumors. We detected that each of
      the 29 samples of CCC and high-grade serous carcinoma (HGSC) were necessary to
      reveal the significant differences in immunostaining and prognosis. We performed
      the immunostaining analysis using the antibodies of cell cycle-related proteins
      such as Ki-67, Cdt1, MCM7, and geminin. The positive rate of Cdt1 in the CCC
      group was significantly higher than that in the HGSC group (P<0.0001). However,
      the positive rate of geminin in the HGSC group was significantly higher than that
      in the CCC group (P<0.0001). The overall survival of CCC patients with high
      labeling index of Cdt1 was significantly worse than that of CCC patients with low
      labeling index of Cdt1 (P=0.004). The study results suggested that the cancer
      cells of CCC and HGSC exist in the G1 phase and S, G2, and M phases,
      respectively. The differences in cell cycle of CCC might be one of the reasons
      for chemotherapy resistance. Further investigations are necessary to reveal the
      usefulness of Cdt1 as a biomarker in CCC.

PMID- 29019870
TI  - Neuroendocrine Tumors of the Fallopian Tube: Report of a Case Series and Review
      of the Literature.
AB  - Primary neuroendocrine tumors of the fallopian tube are extremely rare with a few
      reported cases of high-grade neuroendocrine carcinoma and a single report of a
      carcinoid tumor arising in a teratoma. We report 4 cases of probable primary
      neuroendocrine tumors of the fallopian tube (2 carcinoid tumors/low-grade
      neuroendocrine tumors and 2 high-grade neuroendocrine carcinomas) in patients
      aged 49 to 71. These represent the first reported cases of primary tubal
      carcinoid tumor unassociated with a teratoma. We review the published literature
      regarding primary neuroendocrine tumors of the fallopian tube and speculate on
      the possible histogenesis of these neoplasms.

PMID- 29019871
TI  - Despite Diagnostic Morphology, Many Mixed Endometrial Carcinomas Show Unexpected
      Immunohistochemical Staining Patterns.
AB  - Historically, endometrial carcinomas have been classified primarily according to
      their histology. However, the use of immunohistochemistry has become commonplace
      in their evaluation, particularly in diagnostically challenging cases. Our
      objective was to evaluate mixed endometrial carcinomas using a well-established
      panel of biomarkers to assess the consistency and utility of these stains in
      clinical diagnosis. Eighteen cases comprised of various combinations of classical
      serous (SC), endometrioid (EC), and clear cell (CC) morphologies were identified
      and subjected to a panel of immunohistochemical markers including p53, p16, Ki67,
      estrogen receptor, progesterone receptor, and Napsin A. Intensity and extent of
      staining were evaluated on 4-tiered and 5-tiered scales, respectively. The
      typical immunostaining pattern expected for the individual tumor components was
      seen in only 3 cases, while in 15 cases an unexpected pattern was observed with
      at least one immunomarker. By tumor type, the most common unexpected finding in
      EC/SC carcinoma cases was diffuse positivity for p16 and/or estrogen
      receptor/progesterone receptor in both components, while in SC/CC, diffuse
      positivity for p53 in both components was most frequently seen, and in SC/CC/EC,
      Napsin A negativity was most commonly observed. Despite displaying diagnostic
      morphology, components of many mixed endometrial carcinomas may not exhibit
      expected immunohistochemical features. This may be due to the fact that these
      carcinomas arise from a single clone with subsequent divergence, resulting in a
      tumor with both mixed histologic and genetic features. It is important to note
      that these tumors may not demonstrate the immunohistochemical prototype of their
      constituents and should be approached accordingly from a diagnostic perspective.

PMID- 29019873
TI  - Reconstruction left atrium and isolation pulmonary veins of paroxysmal atrial
      fibrillation using single contact force catheter with zero x-ray exposure: A
      CONSORT Study.
AB  - BACKGROUND: Conventional ablation of paroxysmal atrial fibrillation (PAF) is
      associated with radiation risks for patients and laboratory staff. Three
      dimensional (3D) mapping system capable of showing contact force (CF) and
      direction of catheter tip may compensate for nonfluoroscopic safety issues.
      OBJECTIVE: The aim of this study was to investigate the feasibility of zero x-ray
      exposure during reconstruction left atrium (LA) and ablation. METHODS: Single, CF
      catheter, and 3D mapping system were used to reconstruct LA and isolate pulmonary
      veins (PV) in all patients. The patients were randomly divided into 2 groups
      after LA angiography. In group 1, reconstruction LA and isolation PV was
      performed with the help of 3D system (without x-ray), whereas in group 2, x-ray
      and 3D system were utilized to reconstruct LA and ablate PV antrum. After
      ablation, Lasso catheter was used to confirm the PV isolation. All patients were
      followed up to 12 months. RESULTS: A total of 342 PAF patients were continuously
      enrolled. The basic clinical characteristics between the 2 groups had no
      significant difference. Parameters related to the procedure, average procedure
      time, ablation procedure time, average contact force (CF) applied, the percentage
      of time within CF settings, and average power applied during radiofrequency
      application showed no significant difference between the 2 groups. In group 1,
      the average fluoroscopy time before LA reconstruction was similar to that in
      group 2 (2.8 +/- 0.4 vs. 2.4 +/- 0.6 minutes, P = .75). The average fluoroscopy
      time during ablation was significantly lower than that in group 2 (0 vs. 7.6 +/-
      1.3 minutes, P < .001). The total x-ray exposure dose of the procedure in group 1
      was significantly lower than that in group 2 (19.6 +/- 9.4 vs. 128.7 +/- 62.5
      mGy, respectively, P < .001). Kaplan-Meier analysis indicated that there were no
      statistical differences in the probability of freedom from atrial arrhythmia
      (AF/AFL/AT) recurrence at 12 months between group 1 and group 2 (P = .152). The
      success rate after a single ablation procedure and without drugs (Class I/III
      AAD) at 12 months was not significantly different between the 2 groups (67.6%,
      95% confidence interval [CI]: 62%-79.5% in group 1 and 68.9%, 95% CI: 63%-80.7%
      in group 2, P = .207). Procedural-related adverse events showed no significant
      different incidence between group 1 and group 2. A multivariate logistic
      regression analysis of risk factors was performed to evaluate the effectiveness
      outcome, which demonstrated that the percentage of CF (within the investigator
      selected work ranges) during therapy was significantly associated with positive
      outcomes (odds ratio: 3.68; 95% CI: 1.65-10.6, P = .008), whereas the LA
      dimension was negatively associated with effectiveness outcomes (odds ratio:
      0.72; 95% CI: 0.52-0.84, P = .016). CONCLUSIONS: Reconstruction LA and isolation
      PV ablation using single CF-assisted catheter without x-ray exposure was both
      safe and effective. CF was positively associated with effective outcomes and LA
      dimensions negatively with effective ones.

PMID- 29019874
TI  - Injury patterns among various age and gender groups of trauma patients in
      southern Iran: A cross-sectional study.
AB  - Administrative data from trauma referral centers are useful sources while
      studying epidemiologic aspects of injuries. We aimed to provide a hospital-based
      view of injuries in Shiraz considering victims' age and gender, using
      administrative data from trauma research center.A cross-sectional registry-based
      study of adult trauma patients (age >=15 years) sustaining injury through traffic
      accidents, violence, and unintentional incidents was conducted. Information was
      retrieved from 3 hospital administrative databases. Data on demographics, injury
      mechanisms, injured body regions, and injury descriptions; outcomes of
      hospitalization; and development of nosocomial infections were recorded. Injury
      Severity Score (ISS) was calculated by crosswalking from ICD-10 (International
      Classification of Diseases) injury diagnosis codes to AIS-98 (Abbreviated Injury
      Scale) severity codes. Patients were compared based on age groups and gender
      differences.A total of 47,295 trauma patients with a median age of 30
      (interquartile range: 24-44 years) were studied, of whom 73.1% were male and the
      remaining 26.9% were female (M/F = 2.7:1.0). The most common injury mechanisms in
      the male group were car and motorcycle accidents whereas females were mostly
      victims of falls and pedestrian accidents (P < .01). As age increased, a shift
      from transportation-related to unintentionally caused injuries occurred. Overall,
      young men had their most severe injuries on head, whereas elderly women suffered
      more severe extremity injuries. Injury severity was similar between men and
      women; however, elderly had a significantly higher ISS. Although incidence of
      nosocomial infections was independent of victims' age and gender, elderly men had
      a significantly higher mortality rate.Based on administrative data from our
      trauma center, male gender and age >65 years are associated with increased risk
      of injury incidence, prolonged hospitalizations, and in-hospital death following
      trauma. Development of a regional trauma surveillance system may provide further
      opportunities for studying injuries and evaluating preventive actions.

PMID- 29019875
TI  - Anterograde injection of low-dose urokinase salvages free anterolateral thigh
      flap: A case report of safe and effective treatment.
AB  - RATIONALE: A 54-year-old Taiwanese male came to our hospital presented with right
      retromolar mucoepidermoid carcinoma. Composite resection and right modified
      radical neck dissection were performed. We then use free anteral lateral thigh
      flap to reconstruct the defect. However, venous congestion was found 32 h after
      the surgery. PATIENT CONCERNS: The main concerns of the patient is complete
      salvage of the free flap, and avoiding the secondary free flap harvesting and
      reconstruction surgeries. DIAGNOSES: Right retromolar mucoepidermoid carcinoma.
      INTERVENTIONS: We report the case of a patient with an anterolateral thigh flap
      with venous perianastomosis thrombosis and intraflap microvascular thrombosis
      successfully salvaged using anterograde intra-arterial injection of low-dose
      urokinase (60,000 U), without administering intravenous anticoagulation heparin
      during the postoperative period. OUTCOMES: The flap was completely salvaged 3
      days after treatment. No other flap-associated or bleeding complications were
      noted. The intra-oral wounds around the flap completely healed without any post
      ischemic complications. LESSONS SUBSECTIONS: Although the ideal urokinase doses
      and delivery procedures for free flap salvage have not been developed thus far,
      our method maximizes the urokinase gradient in the flap, minimizes the total dose
      required for flap salvage, and ensures no systemic spread. Thus, compared with
      other thrombolytic agents, urokinase may be more effective and safe for free flap
      salvage. With more experience, a standardized dosage and procedure can be
      developed.

PMID- 29019876
TI  - Unique circumferential peripheral keratitis in relapsing polychondritis: A case
      report.
AB  - RATIONALE: Relapsing polychondritis (RP) is a rare collagen disease characterized
      by inflammation and destruction of cartilage throughout the body. The paper
      details the clinical course of a case of RP with unique circumferential
      peripheral keratitis. PATIENT CONCERNS: A 54-year-old Japanese woman was referred
      to the hospital presenting with auricular and ocular pain. DIAGNOSES: Based on
      the auricle biopsy results and the three presenting symptoms (bilateral auricular
      chondritis, inflammatory arthritis and ocular inflammation), her condition was
      diagnosed as RP. INTERVENTIONS: The three presenting symptoms gradually improved
      with prednisolone (PSL), methylprednisolone and cyclophosphamide combination
      therapy, followed by PSL, methotrexate and infliximab combination therapy.
      However, one month after the initial visit, despite ongoing treatment, a unique
      circumferential peripheral keratitis suddenly occurred, in which the corneal
      infiltration gradually clumped together and shrank at the peripheral area. The
      eye and ear pain showed exacerbations and remissions on reducing the dosage of
      steroid drugs. The general condition was improved on altering systemic therapy to
      PSL, methotrexate and tocilizumab. OUTCOMES: Keratitis gradually disappeared
      within 10 months of the initial visit. LESSONS: This is the first report of a
      case of RP causing unique circumferential peripheral keratitis. This keratitis
      occurred despite use of focal and systemic steroids and showed improvement with
      general recovery. This may indicate that stabilization of general condition is
      important for recovery from keratitis in RP.

PMID- 29019877
TI  - A spontaneous hematoma arising within an intrapancreatic accessory spleen: A case
      report and literature review.
AB  - RATIONAL: Hematoma arising within an intrapancreatic accessory spleen (IPAS) is
      an extremely rare pathological entity. PATIENT CONCERN: We present the case of a
      39-year-old man with acute abdominal pain. DIAGNOSES: The patient was initially
      diagnosed as pancreatic cystic neoplasm according to CT and MRI imaging.
      INTERVENTIONS: Distal pancreatectomy was conducted because of the possibility of
      malignancy. OUTCOMES: Surgical resection showed that the lesion was a hematoma in
      an IPAS. LESSONS: Our case indicated that the differential diagnosis of hematoma
      in IPAS should be born in mind for cases with cystic neoplasm in tail of pancreas
      and an epidermoid cyst arising within an intrapancreatic accessory spleen
      (ECIAS).

PMID- 29019878
TI  - A comparison of anterior cervical discectomy and fusion combined with cervical
      disc arthroplasty and cervical disc arthroplasty for the treatment of skip-level
      cervical degenerative disc disease: A retrospective study.
AB  - Anterior cervical discectomy and fusion (ACDF) has been widely performed for the
      treatment of multilevel cervical degenerative disc disease (CDDD). In recent
      decades, cervical disc arthroplasty (CDA) and hybrid surgery (HS) have been
      developed to overcome the shortcomings of ACDF. Controversy still remains with
      regard to the optimal surgical procedure for skip-level CDDD.A total of 55
      patients who received surgical treatment for skip-level CDDD in our department
      were reviewed. The patients were divided into the HS group (n = 29) and the CDA
      group (n = 26). The collected data included Japanese Orthopedic Association
      (JOA), Neck Disability Index (NDI), and Visual Analog Scale (VAS) scores, and
      cervical lordosis (CL), range of motion (ROM), and intervertebral disc height
      (IDH). Radiological changes at the intermediate segment (IS) were also collected.
      All data were collected preoperatively and at routine postoperative intervals of
      1 week and 3, 6, and 12 months and at the last follow-up period.Compared with
      preoperative values, mean JOA, NDI, and VAS scores significantly improved after
      surgery in both the HS and CDA groups (P < .05). However, there were no
      significant differences between the groups (P > .05). The HS group had better CL
      recovery than the CDA group after surgery (P < .05). There was no significant
      difference in the ROM of C2-C7 between the 2 groups (P > .05). A significant
      difference in the ROM of the IS was found at the last follow-up between the 2
      groups (P < .05). At the last-follow-up, 4 discs (14.29%) in the CDA group and 6
      discs (19.36%) in the HS group had adjacent segment degeneration (ASD) without
      symptoms.Both HS and CDA might be considered safe and effective surgical
      strategies for the treatment of skip-level CDDD. Although the clinical outcomes
      were similar in the 2 groups, CDA altered the ROM of the IS to a lesser degree.

PMID- 29019879
TI  - Percutaneous coronary intervention versus cardiac bypass surgery for left main
      coronary artery disease: A trial sequential analysis.
AB  - BACKGROUND: Several updated meta-analyses comparing percutaneous coronary
      intervention (PCI) with coronary artery bypass grafting (CABG) for left main
      coronary artery disease (LM CAD) have been published recently. However, the risk
      of false-positive results could be high in conventional updated meta-analyses due
      to repetitive testing of accumulating data. Therefore, we compared these
      treatment approaches via trial sequential analysis (TSA). METHODS: The MEDLINE,
      Embase, and Cochrane Central Register of Controlled Trials databases were
      searched for published randomized controlled trials (RCTs) or subgroups of RCTs
      comparing PCI and CABG in patients with LM CAD. The primary outcome was major
      cardiac and cerebrovascular adverse events (MACCE). TSA was used to confirm the
      conclusions derived from conventional meta-analysis. RESULTS: Six RCTs with 4700
      patients were included. PCI was associated with a greater risk of MACCE compared
      with CABG (pooled relative risk [RR] 1.21, 95% confidence interval [CI]: 1.05
      1.40, P = .008). In addition, PCI resulted in a significantly higher risk of
      revascularization than CABG (pooled RR 1.61, 95% CI: 1.33-1.95, P < .0001). TSA
      provided firm evidence for the reduction of MACCE and revascularization with CABG
      compared with PCI (cumulative z-curve crossed the monitoring boundary). In the
      subgroup analysis, CABG was better than PCI in patients with SYNTAX score >32
      (pooled RR 1.41, 95% CI: 1.12-1.76, P = .003), which was confirmed by the TSA.
      There was no difference in patients with a SYNTAX score from 0 to 32.
      CONCLUSIONS: In patients with LM CAD, CABG may be better than PCI for reducing
      MACCE due to a reduced risk of revascularization. CABG remains the first choice
      for LM CAD patients with high anatomic complexity, while PCI could be an
      alternative for those with low-to-moderate anatomic complexity.

PMID- 29019880
TI  - The effect of water immersion delivery on the strength of pelvic floor muscle and
      pelvic floor disorders during postpartum period: An experimental study.
AB  - BACKGROUND: Water immersion delivery is a non-pharmacological approach to ease
      labor pain. This paper aims to investigate the effect of water immersion delivery
      on increasing strength of pelvic floor muscle (PFM) and relieving pelvic floor
      disorders (PFDs) during postpartum period. METHODS: A total of 2749 vaginal
      delivery primiparas in postpartum 6-8 weeks were selected as research objects.
      Based on the modes of delivery, 600 patients were assigned into water immersion
      delivery group, 2149 were assigned into conventional delivery group. The scales
      of PFM strength and pelvic organ prolapsed (POP) were determined by specially
      trained personnel using digital palpation, and the symptoms of stress urinary
      incontinence (SUI) were investigated by questionnaire survey. The weak PFM
      strength was improved by doing Kegel exercise at home for 6-8 weeks. RESULTS: We
      found that 1The rate of episiotomy in water immersion delivery group was 77.50%
      (465/600), which was lower than that in conventional delivery group (84.69%,
      1820/2149) (P < .01); The primiparas without having an episiotomy have higher PFM
      strength than those having an episiotomy for both groups (P < .01). 2There was a
      negative correlation between the scale of PFM strength and SUI or POP, wherein
      the r-values were -0.135 and -0.435, respectively (P < .01). 3The rate of SUI was
      6.50% (39/600) in water immersion delivery group and 6.89% (148/2149) in the
      conventional delivery group, wherein the intergroup difference was not
      significant (P > .05); 4The rates of vaginal wall prolapsed and uterus prolapsed
      were 29.83% (179/600) and 2.83% (17/600) in water immersion delivery group and
      30.95% (665/2149) and 4.37% (94/2149) in the conventional delivery group, wherein
      the intergroup difference was not significant (P > .05). 5After Kegel exercise,
      the strength of PFM was promoted (P < .01). CONCLUSION: Water immersion delivery
      has been proved to a beneficial alternative method for conventional delivery
      method. This delivery mode is associated with fewer episiotomy rate, and avoiding
      episiotomy is beneficial for maintaining PFM strength of women in postpartum 6-8
      weeks. The strength of PFM during postpartum period can be improved by doing
      Kegel exercise at home.

PMID- 29019881
TI  - Assessment of left ventricular performance in heart transplant recipients by
      three-dimensional speckle tracking imaging.
AB  - To calculate left ventricular (LV) global performance values in heart transplant
      (HT) recipients by three-dimensional speckle tracking imaging (3D-STI) and to
      observe the changes in LV global performance over time after HT and investigate
      the correlated factors.The 30 HT patients were divided into 2 groups according to
      postoperative time: 1 month postoperatively (HT-1) group and 6 months
      postoperatively (HT-2) group. Thirty healthy subjects were enrolled as control
      group. 3D-STI was performed to assess LV torsion, LV systolic dyssynchrony index
      (SDI), and LV global strain (GS). Global performance index (GPI) was calculated,
      and correlations factors with GPI were studied.Heart rate (HR), left atrium (LA),
      interventricular septum thickness (IVST), left ventricular posterior wall
      thickness (LVPWT), and left ventricular mass (LVM) in both HT groups were higher
      than those in the control group. Compared with the control group, SDI was
      significantly higher in both HT groups, and SDI of the HT-1 group was much higher
      than that of HT-2 group. Compared with the control group, apical rotation (RoA),
      twist and torsion in the both HT groups decreased significantly. There were no
      significant differences in these values between the 2 HT groups; Basal rotation
      (RoB) showed no significantly difference among the 3 groups. GS in the both HT
      groups decreased significantly compared with the control group, and there were no
      significant differences in these values between the 2 HT groups. GPI of the both
      HT groups was significantly lower than that of the control group; however, GPI of
      HT-2 group was higher than that of HT-1 group. Multivariate stepwise regression
      analysis identified global left ventricular longitudinal peak systolic strain
      (GLS), the time length since surgery, left ventricular mass (LVM), and RoA as
      predictors of LV GPI. GLS was the most influential to GPI.The values of LV
      rotation, twist and SDI can be used to assess the LV systolic function and
      dyssynchrony. The GPI value based on 3D-STI may accurately reflect LV performance
      changes over time after HT. The GPI value has potential applications in clinical
      practice. GLS, the time length since surgery, LVM and RoA values can be the
      predictors of LV global performance, and as long as the left ventricular ejection
      fraction (LVEF) is preserved, the left ventricular global performance of HT
      recipients remains stable, and tends to improve over time after HT.

PMID- 29019882
TI  - Koebner phenomenon induced by failed revisional orthopedic surgery but remitted
      with bone union: A case report.
AB  - RATIONALE: Trauma or surgical incision might cause Koebner phenomenon (KP) in
      patients with cutaneous diseases, but seldom studies reported KP induced by
      repeated orthopedic surgery. PATIENT CONCERNS: The 22-year-old man did not have
      any prior histories of cutaneous diseases. Two months after the revision surgery
      for nonunion of the left femoral shaft fracture, KP was noted by psoriasis
      presented at the surgical scar, left thigh, scalp, and trunk. Phototherapy and
      topical treatments were prescribed but the effect was limited. DIAGNOSIS: KP
      induced by failed revisional orthopedic surgery. INTERVENTIONS: Because of
      implant failure, he underwent the second revision surgery, which was performed on
      the previous scar surrounded and covered by psoriatic plaques. OUTCOMES: After
      the second revision surgery successfully corrected the orthopedic problem, the
      psoriatic lesion remitted along with the bone union. LESSONS: In a patient having
      KP, to perform an operation on psoriatic lesion sites was safe and the surgical
      wound could heal well. The most important to treat KP induced by orthopedic
      surgery might be the underlying bone stability.

PMID- 29019883
TI  - Bone mineral density changes of lumbar spine and femur in osteoporotic patient
      treated with bisphosphonates and beta-hydroxy-beta-methylbutyrate (HMB): Case
      report.
AB  - RATIONALE: Currently available approaches to osteoporosis treatment include
      application of antiresorptive and anabolic agents influencing bone tissue
      metabolism. The aim of the study was to present bone mineral density (BMD)
      changes of lumbar spine in osteoporotic patient treated with bisphosphonates such
      as ibandronic acid and pamidronic acid, and beta-hydroxy-beta-methylbutyrate
      (HMB). PATIENT CONCERNS: BMD and volumetric BMD (vBMD) of lumbar spine were
      measured during the 6 year observation period with the use of dual-energy X-ray
      absorptiometry (DEXA) and quantitative computed tomography (QCT). DIAGNOSES: The
      described case report of osteoporotic patient with family history of severe
      osteoporosis has shown site-dependent response of bone tissue to antiosteoporotic
      treatment with bisphosphonates. INTERVENTIONS AND OUTCOMES: Twenty-five-month
      treatment with ibandronic acid improved proximal femur BMD with relatively poor
      effects on lumbar spine BMD. Over 15-month therapy with pamidronic acid was
      effective to improve lumbar spine BMD, while in the proximal femur the treatment
      was not effective. A total of 61-week long oral administration with calcium salt
      of HMB improved vBMD of lumbar spine in the trabecular and cortical bone
      compartments when monitored by QCT. Positive effects of nearly 2.5 year HMB
      treatment on BMD of lumbar spine and femur in the patient were also confirmed
      using DEXA method. LESSONS: The results obtained indicate that HMB may be applied
      for the effective treatment of osteoporosis in humans. Further studies on wider
      human population are recommended to evaluate mechanisms influencing bone tissue
      metabolism by HMB.

PMID- 29019884
TI  - Utility of osteosclerotic lesion biopsy in diagnosis of POEMS syndrome: A case
      report.
AB  - RATIONALE: We report a case of successful diagnosis of POEMS (polyneuropathy,
      organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome
      based on monoclonality that was confirmed by an osteosclerotic lesion biopsy in a
      patient without pathognomonic symptoms or monoclonal gammopathy, probably because
      of comorbidities, which included systemic lupus erythematosus, rheumatoid
      arthritis, and Sjogren syndrome. PATIENT CONCERNS: A 57-year-old woman presented
      with an approximately 2-year history of numbness in the toes that had gradually
      spread, along with muscle weakness in both arms and legs. She had been receiving
      immunosuppressant and corticosteroid therapy since being diagnosed with systemic
      lupus erythematosus and Sjogren syndrome at the age of 31 years and rheumatoid
      arthritis at the age of 44 years. Neurological examination revealed predominantly
      distal hypoesthesia and weakness in a typical stocking-and-glove pattern.
      Immunoelectrophoresis revealed elevated polyclonal immunoglobulin, which was
      attributed to her known underlying disease. DIAGNOSES: Biopsy of an
      osteosclerotic lesion confirmed proliferation of monoclonal plasma cells, leading
      to a diagnosis of POEMS syndrome. INTERVENTIONS AND OUTCOMES: Lenalidomide
      therapy was started after the diagnosis and the patient had a favorable outcome.
      LESSONS: Osteosclerotic lesion biopsy can be useful for diagnosis of POEMS
      syndrome in difficult cases.

PMID- 29019885
TI  - Two-incision laparoscopic appendectomy for a severe hemophilia A child patient
      with coagulation factor VII deficiency: Case report and review of literature.
AB  - RATIONALE: The main complication of patients with severe hemophilia is recurrent
      bleeding events that usually affected musculoskeletal contractures. And
      replacement therapy methods were continuously improved to minimize adverse
      impacts brought by those complications. However, only several cases reported
      about the appendectomy for hemophilia A. We report a case of acute appendicitis
      treated by two-incision laparoscopy in a boy with hemophilia A and coagulation
      factor VII deficiency for the first time. PATIENT CONCERNS: An 8y7m-old Chinese
      boy presented with half a day of right sided abdominal pain, fever, nausea, and
      vomiting. DIAGNOSES: He received a computed tomography (CT) scan which revealed
      an enlarged appendix, thickened wall and appendiceal fecalith, and had received a
      conservative anti-bacterial treatment for his acute appendicitis but failed. He
      was diagnosed with hemophilia A and coagulation factor VII deficiency.
      INTERVENTIONS: Two-incision laparoscopic appendectomy was made in success with a
      careful management of perioperative period. We monitored the clotting factor
      FVIII level and gave him a replacement therapy. OUTCOMES: The patient had an
      uneventful recovery. LESSONS: It is important to exclude intraabdominal or
      retroperitoneal hemorrhage in patients suffering from hemophilia and acute
      abdominal pain. Pre-operative evaluation of validity of the FVIII replacement
      therapy is another effective strategy to assess the safety and feasibility of
      applying an operation procedure. The two-incision laparoscopic appendectomy is an
      effective treatment for this kind of patients for its minimal trauma and fast
      recovery characteristics. Our report shows that laparoscopic appendectomy is
      feasible in a child suffering from hemophilia after adequate blood clotting
      factor replacement treatment.

PMID- 29019886
TI  - A hospital-to-home evaluation of an enhanced recovery protocol for elective
      pancreaticoduodenectomy in China: A cohort study.
AB  - Enhanced recovery after surgery (ERAS) programs have been shown to decrease
      postoperative complications and hospital stay in pancreaticoduodenectomy.
      However, no studies concerned recovery after discharge except readmission. This
      study evaluated an ERAS program for pancreaticoduodenectomy from hospital to
      home.A prospective ERAS cohort undergoing elective pancreaticoduodenectomy was
      compared with a retrospective control group in terms of postoperative
      complications and hospital stay, and home recovery after discharge. Propensity
      score matching was used to balance their baselines.Two groups of 31 patients with
      similar propensity scores were established. Postoperative morbidities were 18 of
      31 and 26 of 31 in the ERAS and control groups, respectively (P = .06). Patients
      in the ERAS group suffered from fewer cardiovascular complications (3/31 vs
      11/31; P = .04) and intestinal dysbacteriosis (4/31 vs 13/31; P = .04). Median
      postoperative hospital stay was shorter in the ERAS group (8 vs 16 days; P <
      .001). Although the 2 groups were similar in terms of sleep, defecation, vigor,
      performance status, and pain control in first month after discharge, patients in
      the ERAS group enjoyed better food intake recovery (18/31 vs 5/31 in first week,
      P = .002; 22/31 vs 9/31 in second week, P = .008; 23/31 vs 13/31 in fourth week,
      P = .01) and fewer weight loss (10/31 vs 19/31; P = .05). Multivariate analyses
      showed that both improvements were associated with no bowel preparation.ERAS
      implementation in selected patients undergoing pancreaticoduodenectomy could
      promise better outcomes, not only in the hospital but also at home in the short
      term.

PMID- 29019887
TI  - Factors predicting a home death among home palliative care recipients.
AB  - Awareness of factors affecting the place of death could improve communication
      between healthcare providers and patients and their families regarding patient
      preferences and the feasibility of dying in the preferred place.This study aimed
      to evaluate factors predicting home death among home palliative care
      recipients.This is a population-based study using a national representative
      sample retrieved from the National Health Insurance Research Database. Subjects
      receiving home palliative care, from 2010 to 2012, were analyzed to evaluate the
      association between a home death and various characteristics related to illness,
      individual, and health care utilization. A multiple-logistic regression model was
      used to assess the independent effect of various characteristics on the
      likelihood of a home death.The overall rate of a home death for home palliative
      care recipients was 43.6%. Age; gender; urbanization of the area where the
      patients lived; illness; the total number of home visits by all health care
      professionals; the number of home visits by nurses; utilization of nasogastric
      tube, endotracheal tube, or indwelling urinary catheter; the number of emergency
      department visits; and admission to intensive care unit in previous 1 year were
      not significantly associated with the risk of a home death. Physician home visits
      increased the likelihood of a home death. Compared with subjects without
      physician home visits (31.4%) those with 1 physician home visit (53.0%, adjusted
      odds ratio [AOR]: 3.23, 95% confidence interval [CI]: 1.93-5.42) and those with
      >=2 physician home visits (43.9%, AOR: 2.23, 95% CI: 1.06-4.70) had higher
      likelihood of a home death. Compared with subjects with hospitalization 0 to 6
      times in previous 1 year, those with hospitalization >=7 times in previous 1 year
      (AOR: 0.57, 95% CI: 0.34-0.95) had lower likelihood of a home death.Among home
      palliative care recipients, physician home visits increased the likelihood of a
      home death. Hospitalizations >=7 times in previous 1 year decreased the
      likelihood of a home death.

PMID- 29019888
TI  - An upper cervical cord compression secondary to occult follicular thyroid
      carcinoma metastases successfully treated with multiple radioiodine therapies: A
      clinical case report.
AB  - RATIONALE: The spine is the most common site of bone metastases due to thyroid
      cancer; however, spinal cord compression as a complication of metastatic thyroid
      cancer is very rare. PATIENT CONCERNS: A 48-year-old female patient was presented
      to the Neurosurgical Department, complaining of progressive back neck pain with
      bilateral upper extremities numbness and weakness for 4 months. DIAGNOSIS:
      Imaging studies revealed osteolytic destruction in bodies and accessories of the
      second and third cervical vertebrae with a huge soft-tissue mass compressing
      spinal cord and causing swelling. After the neurosurgical decompression surgery,
      the pathological examination established a metastatic follicular carcinoma
      originating from the thyroid gland. INTERVENTIONS: Her cervical spinal metastases
      were hardly removed by surgery and the risks of external beam radiation therapy
      (EBRT) were very high. So she underwent a total thyroidectomy and received
      multiple radioiodine (RAI) and concomitant glucocorticoid therapies
      postoperatively. Radioiodine whole-body scan (WBS) showed multiple abnormal
      radioiodine uptakes. Then single-photon emission tomography/computed tomography
      (SPECT/CT) located these spinal metastases involving cervical, lumbar, and sacral
      vertebrae. OUTCOMES: After 5 times RAI therapy, her thyroglobulin obviously
      decreased, with the cervical lesion shrinkage and no spinal cord edema. LESSONS:
      RAI therapy and concomitant glucocorticoid therapy could be used for spinal
      metastases of FTC, even with spinal cord compression.

PMID- 29019889
TI  - High dose of nimustine as an add-on treatment for small cell lung cancer with
      intracranial metastasis: A case report and literature review.
AB  - RATIONALE: Small cell lung cancer (SCLC) characterized by high degree of
      malignancy and rapid tumor progression. Intracranial metastases often appear at
      the time of the initial diagnosis or treatment. Besides of radiotherapy,
      chemotherapy is supposed to have limited effect. PATIENT CONCERNS: A 66-year-old
      male had blurred vision and unsteady step with moderate headache, nausea, vomit.
      DIAGNOSES: The patient was diagnosed with SCLC with intracranial metastases.
      INTERVENTIONS: High dose of nimustine (ACNU) (300 mg/m) add to the regimen
      containing carboplatin and irinotecan. OUTCOMES: Although the patient suffered
      severe myelosuppression, the intracranial lesion almost disappeared and
      maintained half a year. LESSONS: ACNU at a dose of 200 mg/m might be tolerable in
      combination with other chemotherapeutic drugs for the treatment of SCLC with
      intracranial metastases besides radiotherapy.

PMID- 29019890
TI  - External fixation combined with delayed internal fixation in treatment of tibial
      plateau fractures with dislocation.
AB  - The aim of this study was to evaluate the clinical efficacy of external fixation,
      delayed open reduction, and internal fixation in treating tibial plateau fracture
      with dislocation.Clinical data of 34 patients diagnosed with tibial plateau
      fracture complicated with dislocation between January 2009 and May 2015 were
      retrospectively analyzed. Fifteen patients in group A underwent early calcaneus
      traction combined with open reduction and internal fixation and 19 in group B
      received early external fixation combined with delayed open reduction and
      internal fixation. Operation time, postoperative complication, bone healing time,
      knee joint range of motion, initial weight-bearing time, Rasmussen tibial plateau
      score, and knee function score (HSS) were statistically compared between 2
      groups.The mean follow-up time was 18.6 months (range: 5-24 months). The mean
      operation time in group A was 96 minutes, significantly longer than 71 minutes in
      group B (P < .05). In group A, 5 cases had postoperative complications and 1 in
      group B (P < .05). The mean bone healing time in group A was 6.9 months (range: 5
      9 months) and 6.0 months (range: 5-8 months) in group B (P > .05). In group A,
      initial weight-bearing time in group A was (14.0 +/- 3.6) weeks, significantly
      differing from (12.9 +/- 2.8) weeks in group B (P < 0.05). In group A, the mean
      knee joint range of motion was 122 degrees  (range: 95 degrees -150 degrees ) and
      135 degrees  (range: 100 degrees -160 degrees ) in group B (P > 0.05). Rasmussen
      tibial plateau score in group A was slightly lower than that in group B (P >
      .05). The excellent rate of knee joint function in group A was 80% and 84.21% in
      group B (P > .05).External fixation combined with delayed open reduction and
      internal fixation is a safer and more efficacious therapy of tibial plateau
      fracture complicated with dislocation compared with early calcaneus traction and
      open reduction and internal fixation.

PMID- 29019891
TI  - Study protocol for a randomized controlled pilot-trial on the semiocclusive
      treatment of fingertip amputation injuries using a novel finger cap.
AB  - INTRODUCTION: Fingertip amputation injuries are common in all ages.
      Conservatively treated fingertips can regenerate skin and soft tissues to form a
      functionally and cosmetically excellent new fingertip. Little is known about this
      ability that, in humans, is confined to the fingertips. Even less is known about
      the role of the bacteria that regularly colonize these wounds without negative
      impact on regeneration and healing.As an alternative to surgery, self-adhesive
      film dressings are commonly used to establish a wet chamber around the injury.
      These dressings leak malodorous wound fluid eventually until the wound is dry.
      Having that into consideration, we have therefore developed a silicone finger cap
      that forms a mechanically protected, wet chamber around the injury for optimal
      regeneration conditions. It contains a puncturable reservoir for excess wound
      fluid, which can be thus routinely analyzed for diagnostic and research
      purposes.This study protocol explains the first randomized controlled trial (RCT)
      on the semiocclusive treatment of fingertip amputations in both children and
      adults comparing traditional film dressings with the novel silicone finger cap.
      Being the first RCT using 2 medical devices not yet certified for this
      indication, it will gather valuable information for the understanding of
      fingertip regeneration and the design of future definitive studies. METHODS AND
      ANALYSIS: By employing an innovative pseudo-cross-over-design with a dichotomous
      primary endpoint based on patients preference, this pilot study will gain
      statistically significant data with a very limited sample size. Our RCT will
      investigate acceptance, safety, effectiveness, and efficacy of this novel medical
      device while gathering information on the clinical course and outcome of
      conservatively treated fingertip injuries. A total of 22 patients older than 2
      years will be randomly assigned to start the conservative treatment with either
      the traditional film-dressing or the novel finger cap. The treatment will be
      changed to the other alternative for another 2 weeks before the patient or the
      guardian is confronted with the decision of which method they would prefer for
      the rest of the treatment (if required). ETHICS AND DISSEMINATION: Ethical
      approval (EK 148042015) of the study protocol has been obtained from
      Institutional Review Board at the TU Dresden. The trial is registered at the
      European Database on Medical Devices (EUDAMED-No.: CIV-15-03-013246) and at
      ClinicalTrials.gov (NCT03089060).

PMID- 29019892
TI  - Bright sinus appearance on arterial spin labeling MR imaging aids to identify
      cerebral venous thrombosis.
AB  - Cerebral venous thrombosis is a potentially lethal disease. Early diagnosis is
      essential to improve its prognosis. However, its early diagnosis based on
      conventional imaging modalities remains a challenge in clinical settings. The
      purpose of this study was to evaluate whether bright sinus appearance on arterial
      spin-labeling perfusion-weighted image (ASL-PWI) could help identify cerebral
      venous thrombosis.ASL-PWI of 13 patients who were confirmed as cerebral venous
      thrombosis based on neurologic symptoms and computed tomography (CT) or magnetic
      resonance (MR) venography (with/without cerebral angiography) were
      retrospectively analyzed for the presence or absence of the following: bright
      signal in dural sinus termed "bright sinus appearance"; and hypoperfusion in
      brain parenchyma drained by thrombosed sinus. In addition, conventional MR
      findings, including susceptibility vessel sign, empty delta sign, and atypical
      distribution against arterial territory, were also analyzed.Bright sinus
      appearance on ASL-PWI was found in all (100%) 13 patients. In addition, 10 (77%)
      patients showed hypoperfusion in the brain parenchyma drained by thrombosed sinus
      on ASL-PWI. Susceptibility vessel sign and empty delta sign were revealed in 11
      (85%) and 7 (54%) patients, respectively. Atypical distribution against arterial
      territory was seen in 5 (50%) of the 10 patients with parenchymal abnormality on
      conventional MR sequences. Therefore, the bright sinus appearance had higher
      sensitivities for identifying cerebral venous thrombosis than the susceptibility
      vessel sign, empty delta sign, and atypical distribution against arterial
      territory (with differences of 15%; P = .500, 46%; P = .031, and 50%; P = .031,
      respectively).Bright sinus appearance on ASL-PWI can provide important diagnostic
      clue for identifying cerebral venous thrombosis. Therefore, this technique may
      have the potential to be used as a noninvasive diagnostic tool to identify the
      cerebral venous thrombosis.

PMID- 29019893
TI  - Rescue therapeutic strategy combining ultra-protective mechanical ventilation
      with extracorporeal CO2 removal membrane in near-fatal asthma with severe
      pulmonary barotraumas: A case report.
AB  - RATIONALE: Mechanical ventilation of severe acute asthma is still considered a
      challenging issue, mainly because of the gas trapping phenomenon with the
      potential for life-threatening barotraumatic pulmonary complications. PATIENT
      CONCERNS: Herein, we describe 2 consecutive cases of near-fatal asthma for whom
      the recommended protective mechanical ventilation approach using low tidal volume
      of 6 mL/kg and small levels of PEEP was rapidly compromised by giant
      pneumomediastinum with extensive subcutaneousemphysema. DIAGNOSES: Near fatal
      asthma. INTERVENTION: A rescue therapeutic strategy combining extracorporeal CO2
      removal membrane with ultra-protective extremely low tidal volume (3 mL/kg)
      ventilation was applied. OUTCOMES: Both patients survived hospital discharge.
      LESSONS: These 2 cases indicate that ECCO2R associated with ultra-protective
      ventilation could be an alternative to surgery in case of life-threatening
      barotrauma occurring under mechanical ventilation.

PMID- 29019894
TI  - Randomized controlled trial of late-course concurrent versus sequential
      chemoradiotherapy after mastectomy and axillary surgery in locally advanced
      breast cancer.
AB  - BACKGROUND: Concurrent chemoradiotherapy could increase the local control rate in
      patients with high recurrence risk after breast-conserving surgery, but the
      effect of concurrent chemoradiotherapy after mastectomy and axillary dissection
      is not clear. The aim of the study was to compare the effects of late-course
      concurrent chemoradiotherapy (CCRT) versus sequential therapy (SCRT) after
      mastectomy and axillary surgery in locally advanced breast cancer. METHODS: This
      was a randomized controlled trial of 155 patients with stage pT3-4p N1-3c M0 or
      pAnyT pN2-3c M0 breast cancer undergoing 5
      fluorouracil+epirubicin+cyclophosphamide followed by docetaxel (FEC-D)
      chemotherapy after mastectomy and axillary dissection. Patients were randomized
      to the CCRT group (intensity-modulated radiation therapy was performed
      concurrently with docetaxel) or to the SCRT group (radiotherapy after
      chemotherapy). Recurrences, adverse reactions, and short-term effects were
      observed. RESULTS: All the patients completed the planned therapy. The median
      follow-up was 39 (range, 16-62) months. Compared with SCRT, the 3-year local
      regional recurrence-free survival (LRFS) in the CCRT group was improved (81.8% vs
      92.3%, P = .046). There was no significant difference in 3-year disease-free
      survival (DFS) and overall survival (OS). In the pT3-4 pN1-3 cM0 subgroup, the 3
      year local recurrence-free survival and DFS were significantly improved in the
      CCRT group (69.4% vs 88.2%, P = .036; and 41.7% vs 72.6%, P = .049,
      respectively). No significant difference was observed adverse reactions between
      the 2 groups. CONCLUSION: LRFS of patients with locally advanced invasive breast
      cancer after mastectomy and axillary surgery was better with CCRT than with SCRT
      and with similar profiles of adverse reactions. The DFS of patients staged pT3-4
      pN1-3 cM0 was also improved.

PMID- 29019895
TI  - The prognostic value of PCNA expression in patients with osteosarcoma: A meta
      analysis of 16 studies.
AB  - BACKGROUND: Numerous studies have attempted to determine the prognostic role of
      proliferating cell nuclear antigen (PCNA) expression in patients with
      osteosarcoma with no consistent conclusion. We performed this meta-analysis to
      systematically elucidate the association in a more precise manner.The purpose of
      this meta-analysis is to determine the prognostic role of PCNA in patients with
      osteosarcoma. METHODS: A systematic search of relevant studies was performed in 6
      electronic databases including PubMed, Embase, Web of Science, Wanfang database,
      China National Knowledge Internet (CNKI) database, and Chinese Biological Medical
      (CBM) Database (up to March 1, 2016) with the following keywords: (PCNA OR
      proliferating cell nuclear antigen) AND (osteosarcoma OR osteogenic tumor). A
      manual search of references on relevant articles was also conducted by 2
      investigators independently. We performed a comprehensive evaluation of the
      correlation between PCNA expression and overall survival (OS) or disease-free
      survival (DFS) by calculating relative ratios (RR) and their corresponding 95%
      confidence intervals (CI) using STATA software. A fixed- or random-effect model
      was chosen based on the between-study heterogeneity. RESULTS: In total, 16
      studies with 691 osteosarcoma patients were included in this meta-analysis. PCNA
      overexpression was found in approximately 57.31% of the patients with
      osteosarcoma. The meta-analysis suggested that PCNA overexpression in
      osteosarcoma patients is associated with low OS, but not significantly with DFS
      (RR = 1.82, 95% CI 1.53-2.18, P = .000; RR = 1.15, 95% CI 0.91-1.44, P = 0.234).
      Sensitivity analysis for OS and DFS showed no significant difference and the
      pooled RRs were stable when the included studies were removed one by one. Similar
      results were also obtained for subgroup analysis based on different follow-ups
      and cutoffs to determine PCNA expression. CONCLUSION: The findings from this meta
      analysis indicate that PCNA overexpression is an effective biomarker for poor
      prognosis in patients with osteosarcoma for OS. Hence, more large-scale studies
      are still needed to further warrant this conclusion.

PMID- 29019896
TI  - The efficacy of retroperitoneal laparoscopic deroofing of simple renal cyst with
      perirenal fat tissue wadding technique: A retrospective study.
AB  - Treatment options for simple renal cyst (SRC) include open surgery, laparoscopy
      with decortication, or percutaneous aspiration with or without sclerotherapy.
      Though laparoscopic unroofing achieves better results than percutaneous
      sclerotherapy, the reported recurrence rate is still up to 19%. Thus, it is
      necessary to find methods to reduce the recurrence rate.To investigate whether
      the perirenal pedicled fat tissue wadding technique during retroperitoneal
      laproscopic deroofing (RLD) of SRC affects the incidence of recurrence.A
      retrospective analysis was carried out on clinical data of 254 patients with SRC
      treated by RLD in our hospital from 2008 to 2016. Among these patients,119 had a
      simple retroperitoneal deroofing (SRD) and 135 received a retroperitoneoscopic
      deroofing with wadding of the cyst using perirenal fat tissue (RDCW). The
      recurrence rate and variables, as well as perioperative complications, were
      compared. To further explore the potential variables influencing cyst recurrence
      rate, univariate and multivariate regression analyses were applied.A total of 251
      patients were included in the analysis. The operation was successfully completed
      laparoscopically in all cases with no conversion to open surgery. No mortality or
      significant complication occurred in both groups. After a median follow-up of
      38.67 months, we noted 41 recurrences. According to the univariate and
      multivariate regression analyses, patients managed with the wadding technique had
      superior recurrence-free survival (RFS), compared with patients in SRD group (log
      rank P = .03 and P = .04, respectively). Moreover, patients with single renal
      cyst had a lower recurrence rate, compared with patients with multiple renal
      cysts (log-rank P < .01). Regarding the operation time, blood loss, and hospital
      stay, no statistically significant difference was found between 2 groups (P
      values .13, .30, and .75, respectively). However, less postoperative drainage and
      shorter postoperative interval until tube removal (P = .04) were observed in RDCW
      group.The perirenal pedicled fat tissue wadding technique can decrease the cyst
      recurrence rate and RCDW represents an effective and safe treatment option in the
      management of renal cysts.

PMID- 29019897
TI  - Endocan expression is correlated with poor progression-free survival in patients
      with pancreatic neuroendocrine tumors.
AB  - Endocan expression has been reported to be associated with aggressive tumor
      progression and poor outcomes in various cancers, such as breast cancer, renal
      cell cancer, lung cancer, gastric cancer, and pituitary adenomas. However, the
      prognostic significance of endocan in neuroendocrine tumors remains unknown.
      Thus, the aim of this study was to determine the correlation between endocan
      expression in pancreatic neuroendocrine tumor (PNET) tissues and progression-free
      survival. This study included 73 patients with confirmed PNETs who were treated
      in a single tertiary center in north Taiwan between 1992 and 2015.
      Immunohistochemical endocan expression and microvessel density (MVD) were
      examined, and the relationships between these parameters and other
      clinicopathological characteristics were analyzed. The abovementioned patients
      were divided into groups according to their endocan expression levels (>=1% or
      <1%) and median MVDs. Negative endocan expression (P = .002) and a high MVD (P <
      .001) were significant and favorable prognostic factors for progression-free
      survival. However, positive endocan expression was significantly associated with
      a low MVD (P = .037) and tumor mitosis (Ki-67 index) (P = .028). Multivariate Cox
      regression analysis showed that positive endocan expression (hazard ratio: 4.778,
      P = .018) and lymph node involvement (hazard ratio: 5.121, P = .005) were
      independent prognostic factors for tumor recurrence.In conclusion, endocan
      expression was correlated with poor clinical outcomes in PNETs. Our data
      indicated that endocan expression may be a reliable marker for predicting tumor
      recurrence in patients with PNETs.

PMID- 29019898
TI  - An observational study of the relationship between meaningful use-based
      electronic health information exchange, interoperability, and medication
      reconciliation capabilities.
AB  - Stagnation in hospitals' adoption of data integration functionalities coupled
      with reduction in the number of operational health information exchanges could
      become a significant impediment to hospitals' adoption of 3 critical
      capabilities: electronic health information exchange, interoperability, and
      medication reconciliation, in which electronic systems are used to assist with
      resolving medication discrepancies and improving patient safety. Against this
      backdrop, we assessed the relationships between the 3 capabilities.We conducted
      an observational study applying partial least squares-structural equation
      modeling technique to 27 variables obtained from the 2013 American Hospital
      Association annual survey Information Technology (IT) supplement, which describes
      health IT capabilities.We included 1330 hospitals. In confirmatory factor
      analysis, out of the 27 variables, 15 achieved loading values greater than 0.548
      at P < .001, as such were validated as the building blocks of the 3 capabilities.
      Subsequent path analysis showed a significant, positive, and cyclic relationship
      between the capabilities, in that decreases in the hospitals' adoption of one
      would lead to decreases in the adoption of the others.These results show that
      capability for high quality medication reconciliation may be impeded by lagging
      adoption of interoperability and health information exchange capabilities.
      Policies focused on improving one or more of these capabilities may have
      ancillary benefits.

PMID- 29019899
TI  - Effect of cerebral oxygen saturation on postoperative nausea and vomiting in
      female laparoscopic surgery patients.
AB  - BACKGROUND: The purpose of this study was to investigate effect of cerebral
      oxygen saturation (SCTO2) on postoperative nausea and vomiting (PONV) in female
      patients who underwent laparoscopic surgery. METHODS: This study included 90
      female patients who underwent laparoscopic surgery (60 cases of gynecological
      operations and 30 cases of gallbladder operations). All patients were allocated
      into 3 groups of 30 patients each: group A (gynecological laparoscopic surgery),
      group B (gynecological laparoscopic surgery with mannitol treatment) and group C
      (laparoscopic cholecystectomy surgery). Perioperative SCTO2, mean blood flow
      velocity of vertebral artery (VM), vascular resistance index of vertebral artery
      (RI), and PONV (within 48 hours after surgery) were investigated. RESULTS: No
      differences in age, body weight, operation time, and hemoglobin levels were
      observed among the patients (P > .05). The SCTO2 values for groups B and C were
      lower than those for group A in both brain hemispheres at T4 and T5 (P < .05).
      The VM was higher in group B than in groups A and C at T3 (P < .05), but
      differences in VM were not observed between groups B and C at T4 or T5. However,
      the VM of group A was still lower than the other groups (P < .05), and no
      difference in VM was observed among the 3 groups at T6 (P > .05). The RI was
      higher in group C than in groups A and B at T4 (P < .05). The incidence of PONV
      within 48 hours after surgery was significantly higher in group A than in the
      other 2 groups (P < .05). CONCLUSION: Strategies that maintain normal SCTO2 may
      reduce the incidence of PONV in female patients who underwent laparoscopy surgery
      by reducing perioperative intracranial pressure.

PMID- 29019900
TI  - Methylation analysis of p16, SLIT2, SCARA5, and Runx3 genes in hepatocellular
      carcinoma.
AB  - This study is to investigate the methylation status of multiple tumor suppressor
      1 (p16), secreted glycoprotein 2 (SLIT2), scavenger receptor class A, member 5
      putative (SCARA5), and human runt-related transcription factor 3 (Runx3) genes in
      the peripheral blood of hepatocellular carcinoma (HCC).This is a case-control
      study. The peripheral blood samples were collected from 25 HCC patients, 25
      patients with high risk of HCC (defined as "internal control group"), and 25
      healthy individuals (defined as "external control group"), respectively. Then the
      methylation status of p16, SLIT2, SCARA5, and Runx3 genes in the blood samples
      were analyzed by pyrosequencing. The relationship between the methylation and the
      clinical features of HCC patients were evaluated.The methylation levels in the 7
      CpG loci of p16 gene in HCC patients were low and without statistically
      significant difference (P > .05) compared to the control groups. Although the
      methylation levels of CpG3 and CpG4 in SLIT2 gene loci were higher than those of
      the control groups, there was no statistically significant difference (P > .05).
      However, the methylation rate of CpG2 locus in SCARA5 gene in HCC patients was
      significantly higher (P < .05). And the methylation rates of CpG1, CpG2, CpG3,
      CpG4, CpG5, and CpG8 in Runx3 gene in HCC patients were significantly different
      to that of control groups (P < .05). We also have analyzed the correlations
      between the CpG islands methylation of Runx3 or SCARA5 genes and the age, gender,
      hepatitis B, liver cirrhosis, alpha fetal protein, or hepatitis B surface antigen
      (HBsAg) of the HCC patients, which all showed no significant correlations (P >
      .05).The methylation status of SCARA5 and Runx3 genes are abnormal in HCC
      patients, which may further be used as molecular markers for early auxiliary
      diagnosis of liver cancer.

PMID- 29019901
TI  - Relationship between hematocrit levels and intraocular pressure in men and women:
      A population-based cross-sectional study.
AB  - To assess a possible relationship between hematocrit level and intraocular
      pressure (IOP) in both men and women.Data were collected from medical records of
      individuals examined at a screening center in Israel between the years 2000 and
      2013. Hematocrit levels were categorized as low, normal, and high and by sex; IOP
      values were categorized as < 18 mmHg and >=18 mmHg.Cross-sectional analysis was
      performed on 18,424 subjects of mean (standard deviation) age 46 (10) years (68%
      male). Normal-range hematocrit for men was 42% to 52% and 37% to 47% for women.
      In men, mean [95% confidence interval CI)] IOP values by hematocrit level were as
      follows: below-normal hematocrit, 13.3 mmHg (13.2-13.3), normal hematocrit, 13.5
      mmHg (13.4-13.5), above-normal hematocrit, 14.3 mmHg (13.5-15.2) (P < .001).
      Corresponding values in women were 12.9 mmHg (12.8-13.0), 13.0 mmHg (13.0-13.1),
      and 14.2 mmHg (12.9-15.6) (P = .014). The difference remained significant for men
      (P < .001) after adjustment for age, hypertension, diabetes, and body mass index.
      Men (but not women) with a low hematocrit were found to have a significantly
      lower odds ratio (95% CI) of having IOP >=18 mmHg than men with normal
      hematocrit: nonadjusted model, 0.761 (0.631-0.919); adjusted model, 0.771 (0.638
      0.932) (P < .01).It is possible that a raised hematocrit level may also
      contribute to an elevated IOP in men in addition to the classic risk factors.

PMID- 29019903
TI  - An atypical presentation of functional visual loss: A case report.
AB  - RATIONALE: Functional visual loss (FVL) can manifest as various symptoms.
      Decreased distant visual acuity is the most common symptom and visual field
      defect is the second most common symptom. Hemianopsia is rarely reported. In an
      atypical situation of FVL, it is important to prove that no organic pathology
      exists, through detailed history taking and appropriate examinations. PATIENT
      CONCERNS: This review presents the case of a 48-year-old male patient presented
      with decreased bilateral visual acuity and visual field defect after a traffic
      accident 3 weeks ago. Visual field test showed atypical features of FVL in which
      visual field change from binasal hemianopsia to left homonymous hemianopsia.
      DIAGNOSIS: The best corrected visual acuities (BCVA) were 20/63 in both eyes and
      binasal hemianopsia was observed on a Humphrey visual field test. Brain computed
      tomography (CT) scan and magnetic resonance imaging (MRI) showed no abnormalities
      in the brain and optic chiasm. Two weeks after presentation, however, the
      patient's visual field defect changed from binasal hemianopsia to left homonymous
      hemianopsia. We diagnosed it as FVL due to conversion disorder. INTERVENTION AND
      OUTCOMES: We decided to cooperate with a psychiatrist for cognitive behavioral
      therapy and the patient is under observation. LESSONS: Binasal hemianopsia and
      homonymous hemianopsia are rare; however, it may occur simultaneously in 1
      patient with FVL. The possibility of FVL should be considered when there is
      atypical visual field defect and no organic abnormalities are observed. Repeated
      Humphrey field test and VEP may be helpful in diagnosis of FVL.

PMID- 29019902
TI  - In vitro biomechanical comparison after fixed- and mobile-core artificial
      cervical disc replacement versus fusion.
AB  - In vitro biomechanical analysis after cervical disc replacement (CDR) with a
      novel artificial disc prosthesis (mobile core) was conducted and compared with
      the intact model, simulated fusion, and CDR with a fixed-core prosthesis. The
      purpose of this experimental study was to analyze the biomechanical changes after
      CDR with a novel prosthesis and the differences between fixed- and mobile-core
      prostheses.Six human cadaveric C2-C7 specimens were biomechanically tested
      sequentially in 4 different spinal models: intact specimens, simulated fusion,
      CDR with a fixed-core prosthesis (Discover, DePuy), and CDR with a mobile-core
      prosthesis (Pretic-I, Trauson). Moments up to 2 Nm with a 75 N follower load were
      applied in flexion-extension, left and right lateral bending, and left and right
      axial rotation. The total range of motion (ROM), segmental ROM, and adjacent
      intradiscal pressure (IDP) were calculated and analyzed in 4 different spinal
      models, as well as the differences between 2 disc prostheses.Compared with the
      intact specimens, the total ROM, segmental ROM, and IDP at the adjacent segments
      showed no significant difference after arthroplasty. Moreover, CDR with a mobile
      core prosthesis presented a little higher values of target segment (C5/6) and
      total ROM than CDR with a fixed-core prosthesis (P > .05). Besides, the
      difference in IDP at C4/5 after CDR with 2 prostheses was without statistical
      significance in all the directions of motion. However, the IDP at C6/7 after CDR
      with a mobile-core prosthesis was lower than CDR with a fixed-core prosthesis in
      flexion, extension, and lateral bending, with significant difference (P < .05),
      but not under axial rotation.CDR with a novel prosthesis was effective to
      maintain the ROM at the target segment and did not affect the ROM and IDP at the
      adjacent segments. Moreover, CDR with a mobile-core prosthesis presented a little
      higher values of target segment and total ROM, but lower IDP at the inferior
      adjacent segment than CDR with a fixed-core prosthesis.

PMID- 29019904
TI  - Imaging findings of inflammatory myofibroblastic tumor from the greater omentum:
      One case report.
AB  - RATIONALE: Inflammatory myofibroblastic tumors (IMTs) are rare neoplastic lesions
      with benign tendency. Even more rare are IMTs from the greater omentum (GO-IMT).
      A GO-IMT is easily misdiagnosed as other malignant tumors before operation; thus,
      clinicians need to be familiar with its imaging findings. Here, we report the
      imaging findings of a GO-IMT patient presenting with a pelvic mass. PATIENT
      CONCERNS: Ultrasound of the IMT in the pelvic cavity showed a hypoechoic mass. A
      computed tomography (CT) scan showed a nearly circular soft tissue mass with a
      clear border and heterogeneous density, and the surrounding tissues were pushed
      and compressed. Contrast-enhanced CT showed severe persistent enhancement in the
      lesion edges and mural nodules, but not in the central necrosis. DIAGNOSES:
      Histopathology and immunohistochemistry confirmed that the mass was a GO-IMT.
      INTERVENTIONS: The tumor was resected after preoperative preparation. OUTCOMES:
      No recurrence or metastasis was found during a short-term follow-up. LESSONS: The
      GO-IMT is an inferior epigastric mass in the periphery of the bowel, and is
      usually well-demarcated without calcification or lymphadenopathy. Contrast
      enhanced CT showed a heterogeneous hypervascular mass where the center necrosis,
      the edge of the tumor, and the mural nodules can be partially reinforced.

PMID- 29019905
TI  - Bezold-Jarisch reflex occurred in a pediatric patient with giant intra-abdominal
      teratoma during induction of anesthesia: A case report.
AB  - RATIONALE: Bezold-Jarisch reflex (BJR) occurs when the cardioinhibitory receptors
      in the walls of ventricles are activated by various stimuli, with typical
      features of bradycardia, vasorelaxation, and hypotension. This reflex usually
      happens in parturient intrathecal anesthesia, as a result of decreased venous
      return by compression of inferior vena cava, but it is only rarely reported
      during general anesthesia. PATIENT CONCERNS: Severe bradycardia and hypotension,
      indicating BJR, occurred during the induction of general anesthesia in a 3-month
      old female child with giant intra-abdominal teratoma. DIAGNOSES: A giant intra
      abdominal teratoma was detected by computed tomography scanning. The decreased
      left ventricular ejection faction along with increased troponin I and N-terminal
      pro-B-type natriuretic peptide indicated a preoperative mild cardiac dysfunction.
      BJR was diagnosed on the basis of the severe bradycardia and hypotension observed
      during the induction of general anesthesia, INTERVENTIONS:: Atropine failed to
      increase heart rate. Cardiopulmonary resuscitation was initiated immediately and
      epinephrine was injected intravenously because of sudden circulatory collapse.
      Soon after the return of spontaneous circulation, a central venous line was
      placed and invasive blood pressure was monitored. Vital signs and homeostasis
      were kept stable during teratoma resection. OUTCOMES: The child was extubated
      after emergence from anesthesia in the operating room. Eleven days later, she had
      recovered without complications and was discharged. LESSONS: General anesthesia
      should be induced with great care in patients with giant intra-abdominal masses,
      and the patient should be kept in the left-lateral table tilt position before
      induction.

PMID- 29019906
TI  - Predicting Child Protective Services (CPS) Involvement among Low-Income U.S.
      Families with Young Children Receiving Nutritional Assistance.
AB  - This exploratory study examines combinations of income-tested welfare benefits
      and earnings, as they relate to the likelihood of child maltreatment
      investigations among low-income families with young children participating in a
      nutritional assistance program in one U.S. state (Wisconsin). Using a sample of
      1065 parents who received the Special Supplemental Nutrition Assistance Program
      for Women, Infants, and Children (WIC) benefits in late 2010 and early 2011, we
      find that relying on either work in the absence of other means-tested welfare
      benefits, or a combination of work and welfare benefits, reduces the likelihood
      of CPS involvement compared to parents who rely on welfare benefits in the
      absence of work. Additionally, we find that housing instability increases the
      risk of CPS involvement in this population. The findings from this investigation
      may be useful to programs serving low-income families with young children, as
      they attempt to identify safety net resources for their clientele.

PMID- 29019907
TI  - Effect of High-Pressure Treatment on Catalytic and Physicochemical Properties of
      Pepsin.
AB  - For a long time, high-pressure treatment has been used to destroy the compact
      structures of natural proteins in order to promote subsequent enzymatic
      hydrolysis. However, there are few reports evaluating the feasibility of directly
      improving the catalytic capability of proteases by using high-pressure
      treatments. In this study, the effects of high-pressure treatment on the
      catalytic capacity and structure of pepsin were investigated, and the
      relationship between its catalytic properties and changes in its physicochemical
      properties was explored. It was found that high-pressure treatment could lead to
      changes of the sulfhydryl group/disulfide bond content, hydrophobicity,
      hydrodynamic radius, intrinsic viscosity, and subunit composition of pepsin, and
      the conformational change of pepsin resulted in improvement to its enzymatic
      activity and hydrolysis efficiency, which had an obvious relationship with the
      high-pressure treatment conditions.

PMID- 29019908
TI  - Sequencing and Characterization of Novel PII Signaling Protein Gene in Microalga
      Haematococcus pluvialis.
AB  - The PII signaling protein is a key protein for controlling nitrogen assimilatory
      reactions in most organisms, but little information is reported on PII proteins
      of green microalga Haematococcus pluvialis. Since H. pluvialis cells can produce
      a large amount of astaxanthin upon nitrogen starvation, its PII protein may
      represent an important factor on elevated production of Haematococcus
      astaxanthin. This study identified and isolated the coding gene (HpGLB1) from
      this microalga. The full-length of HpGLB1 was 1222 bp, including 621 bp coding
      sequence (CDS), 103 bp 5' untranslated region (5' UTR), and 498 bp 3'
      untranslated region (3' UTR). The CDS could encode a protein with 206 amino acids
      (HpPII). Its calculated molecular weight (Mw) was 22.4 kDa and the theoretical
      isoelectric point was 9.53. When H. pluvialis cells were exposed to nitrogen
      starvation, the HpGLB1 expression was increased 2.46 times in 48 h, concomitant
      with the raise of astaxanthin content. This study also used phylogenetic analysis
      to prove that HpPII was homogeneous to the PII proteins of other green
      microalgae. The results formed a fundamental basis for the future study on HpPII,
      for its potential physiological function in Haematococcus astaxanthin
      biosysthesis.

PMID- 29019909
TI  - Effect of Ge Nanocrystals on 1.54 MUm Photoluminescence Enhancement in Er2O3:ZnO
      and Ge Co-Sputtered Films.
AB  - Photoluminescence (PL) of Er and Ge co-doped ZnO films synthesized by radio
      frequency magnetron co-sputtering was investigated. X-ray diffraction (XRD)
      patterns showed that the annealing process at 400-800  degrees C led to the
      formation of nanocrystal (nc) Ge. Samples containing nc-Ge showed a strong
      visible PL with a peak at 582-593 nm, which was consistent with the calculated
      energy of the exciton of the ~5 nm-sized nc-Ge, according to the quantum
      confinement effect. The formation of nc-Ge could greatly enhance the 1.54 MUm
      emission, and it is considered that the 1.54 MUm PL enhancement may come from a
      joint effect of both the energy transfer from nc-Ge to Er3+ and the local
      environment change of Er3+.

PMID- 29019910
TI  - Determination of Salmonella spp., E. coli VTEC, Vibrio spp., and Norovirus GI-GII
      in Bivalve Molluscs Collected from Growing Natural Beds in Sardinia (Italy).
AB  - The aim of the present study was to evaluate the presence of Salmonella spp.,
      verotoxigenic E. coli (VTEC), Vibrio spp., and Norovirus GI-GII in bivalve
      molluscs, cockles, and European grooved carpet shells (Cerastoderma spp. and
      Ruditapes decussatus) collected from a class B growing natural bed in Sardinia
      (Italy). All of the samples were analysed for Salmonella spp. detection according
      to European Commission Regulation (EC) 2285/2015. Detection and enumeration of
      Vibrio spp. were performed according to previously published methods. Presumptive
      identification of Vibrio spp. isolates was performed by means of conventional
      biochemical tests. E. coli VTEC was isolated following a direct multiplex
      polymerase chain reaction (PCR) screening test. Norovirus GI and GII were
      determined by reverse transcriptase-polymerase chain reaction (RT-PCR). No
      Salmonella spp. were detected. The prevalence of Vibrio spp. was 90%, and the
      average contamination levels were 3.19 +/- 1.07 and 2.84 +/- 0.31 Log10 cfu/g in
      cockles and European grooved carpet shells, respectively. The prevalence of E.
      coli VTEC was 6.6%. All of the isolates showed a complete pathogenicity profile.
      The presence of Norovirus was highlighted in 25% of European grooved carpet
      shells samples. Results showed the typical microbiological profile of bivalve
      molluscs collected from backwaters and confirmed the capability of shellfish to
      accumulate E. coli VTEC, pathogenic vibrios, and Norovirus. The presence of such
      pathogens in shellfish is of major concern for the safety of consumers.

PMID- 29019911
TI  - The Effects of Alkyl Chain Combinations on the Structural and Mechanical
      Properties of Biomimetic Ion Pair Amphiphile Bilayers.
AB  - Ion pair amphiphile (IPA), a lipid-like complex composed of a pair of cationic
      and anionic surfactants, has great potentials in various pharmaceutical
      applications. In this work, we utilized molecular dynamics (MD) simulation to
      systematically examine the structural and mechanical properties of the biomimetic
      bilayers consist of alkyltrimethyl-ammonium-alkylsulfate (CmTMA+-CnS-) IPAs with
      various alkyl chain combinations. Our simulations show an intrinsic one-atom
      offset for the CmTMA+ and CnS- alignment, leading to the asymmetric index
      definition of DeltaC = m - (n + 1). Larger |DeltaC| gives rise to higher
      conformational fluctuations of the alkyl chains with the reduced packing order
      and mechanical strength. In contrast, increasing the IPA chain length enhances
      the van der Waals interactions within the bilayer and thus improves the bilayer
      packing order and mechanical properties. Further elongating the CmTMA+-CnS- alkyl
      chains to m and n >= 12 causes the liquid disorder to gel phase transition of the
      bilayer at 298 K, with the threshold membrane properties of 0.45 nm2 molecular
      area, deuterium order parameter value of 0.31, and effective bending rigidity of
      20 kBT, etc. The combined results provide molecular insights into the design of
      biomimetic IPA bilayers with wide structural and mechanical characteristics for
      various applications.

PMID- 29019913
TI  - Toxic Elements in Different Medicinal Plants and the Impact on Human Health.
AB  - Local medicinal plants from Madina, Saudi Arabia, are used to cure various
      diseases. However, some can cause adverse health effects. Five different
      medicinal plants were collected in the city of Madina: mahareeb (Cymbopogon),
      sheeh (Artemisia), harjal (Cynanchum argel delile), nabipoot (Equisetum), and
      kafmariam (Vitex agnus-castus). In total, four toxic elements including Al, Pb,
      As, and Cd were analyzed using inductively coupled plasma mass spectrometry (ICP
      MS). The range of recoveries fell between 86.1 and 90.6% for all measured
      elements. Al levels were the highest of any of the studied elements in all plant
      samples, with Cymbopogon showing the highest levels. The range of concentrations
      of Al was 156-1609 mg/kg. Cd appeared at the lowest levels in all plants samples,
      with Vitex agnus-castus containing this element at the highest levels. Cd
      concentrations were in the range of 0.01-0.10 mg/kg. A washing process lowered
      the toxic elements in all plants; average % recoveries were Al (47.32%), As
      (59.1%), Cd (62.03%), and Pb (32.40%). The calculated human health risk
      assessment in one dose for toxic elements in all plants was as follows: Al (1.33
      * 10-3-5.57 * 10-2 mg/kg.bw), Pb (0-8.86 * 10-5 mg/kg.bw), As (3.43 * 10-7-1.33 *
      10-5 mg/kg.bw), and Cd (0-3.14 * 10-6 mg/kg.bw). Medicinal plants are a source of
      exposure to toxic elements. However, none of the plants in this study exceeded
      the daily guideline set by the WHO for any element based on conventional use by
      the local population. We may cautiously conclude that these medicinal plants pose
      no risk to users based on conventional use.

PMID- 29019912
TI  - Validation and Assessment of Three Methods to Estimate 24-h Urinary Sodium
      Excretion from Spot Urine Samples in High-Risk Elder Patients of Stroke from the
      Rural Areas of Shaanxi Province.
AB  - Background: 24-h urine collection is regarded as the "gold standard" for
      monitoring sodium intake at the population level, but ensuring high quality urine
      samples is difficult to achieve. The Kawasaki, International Study of Sodium,
      Potassium, and Blood Pressure (INTERSALT) and Tanaka methods have been used to
      estimate 24-h urinary sodium excretion from spot urine samples in some countries,
      but few studies have been performed to compare and validate these methods in the
      Chinese population. Objective: To compare and validate the Kawasaki, INTERSALT
      and Tanaka formulas in predicting 24-h urinary sodium excretion using spot urine
      samples in 365 high-risk elder patients of strokefrom the rural areas of Shaanxi
      province. Methods: Data were collected from a sub-sample of theSalt Substitute
      and Stroke Study. 365 high-risk elder patients of stroke from the rural areas of
      Shaanxi province participated and their spot and 24-h urine specimens were
      collected. The concentrations of sodium, potassium and creatinine in spot and 24
      h urine samples wereanalysed. Estimated 24-h sodium excretion was predicted from
      spot urine concentration using the Kawasaki, INTERSALT, and Tanaka formulas.
      Pearson correlation coefficients and agreement by Bland-Altman method were
      computed for estimated and measured 24-h urinary sodium excretion. Results: The
      average 24-h urinary sodium excretion was 162.0 mmol/day, which representing a
      salt intake of 9.5 g/day. Three predictive equations had low correlation with the
      measured 24-h sodium excretion (r = 0.38, p < 0.01; ICC = 0.38, p < 0.01 for the
      Kawasaki; r = 0.35, p < 0.01; ICC = 0.31, p < 0.01 for the INTERSALT; r = 0.37, p
      < 0.01; ICC = 0.34, p < 0.01 for the Tanaka). Significant biases between
      estimated and measured 24-h sodium excretion were observed (all p < 0.01 for
      three methods). Among the three methods, the Kawasaki method was the least biased
      compared with the other two methods (mean bias: 31.90, 95% Cl: 23.84, 39.97).
      Overestimation occurred when the Kawasaki and Tanaka methods were used while the
      INTERSALT method underestimated 24-h sodium excretion. Conclusion: The Kawasaki,
      INTERSALT and Tanaka methods for estimation of 24-h urinary sodium excretion from
      spot urine specimens were inadequate for the assessment of sodium intake at the
      population level in high-risk elder patients of stroke from the rural areas of
      Shaanxi province, although the Kawasaki method was the least biased compared with
      the other two methods.

PMID- 29019914
TI  - Landscapes and Human Health.
AB  - As urbanization increases around the world and fewer and fewer people have easy
      access to completely natural places, there is a growing need to understand how
      the landscapes we design and inhabit impact our health and wellbeing.[...].

PMID- 29019915
TI  - Revolutionizing Therapeutic Drug Monitoring with the Use of Interstitial Fluid
      and Microneedles Technology.
AB  - While therapeutic drug monitoring (TDM) that uses blood as the biological matrix
      is the traditional gold standard, this practice may be impossible, impractical,
      or unethical for some patient populations (e.g., elderly, pediatric, anemic) and
      those with fragile veins. In the context of finding an alternative biological
      matrix for TDM, this manuscript will provide a qualitative review on: (1) the
      principles of TDM; (2) alternative matrices for TDM; (3) current evidence
      supporting the use of interstitial fluid (ISF) for TDM in clinical models; (4)
      the use of microneedle technologies, which is potentially minimally invasive and
      pain-free, for the collection of ISF; and (5) future directions. The current
      state of knowledge on the use of ISF for TDM in humans is still limited. A
      thorough literature review indicates that only a few drug classes have been
      investigated (i.e., anti-infectives, anticonvulsants, and miscellaneous other
      agents). Studies have successfully demonstrated techniques for ISF extraction
      from the skin but have failed to demonstrate commercial feasibility of ISF
      extraction followed by analysis of its content outside the ISF-collecting
      microneedle device. In contrast, microneedle-integrated biosensors built to
      extract ISF and perform the biomolecule analysis on-device, with a key feature of
      not needing to transfer ISF to a separate instrument, have yielded promising
      results that need to be validated in pre-clinical and clinical studies. The most
      promising applications for microneedle-integrated biosensors is continuous
      monitoring of biomolecules from the skin's ISF. Conducting TDM using ISF is at
      the stage where its clinical utility should be investigated. Based on the
      advancements described in the current review, the immediate future direction for
      this area of research is to establish the suitability of using ISF for TDM in
      human models for drugs that have been found suitable in pre-clinical experiments.

PMID- 29019916
TI  - An Overview of Recent Findings on Social Anxiety Disorder in Adolescents and
      Young Adults at Clinical High Risk for Psychosis.
AB  - BACKGROUND: Some studies have shown that anxiety is particularly frequent in the
      Clinical High Risk (CHR) for psychosis population. Notably, social anxiety
      disorder is identified as one of the most common anxiety disorders in CHR
      adolescents and young adults. Despite this, the frequency and the clinical
      significance of social anxiety in this population have been underestimated.
      METHODS: A selective review of literature published between 2011 and 2017 on
      social anxiety disorder in CHR adolescents and young adults. RESULTS: Five
      studies are included. In particular, three studies demonstrated that CHR
      adolescents and young adults have higher levels of anxiety compared to controls.
      Furthermore, anxiety, including social anxiety, is related to the severity of
      psychotic symptoms. The other studies included show inconsistent results
      regarding the possible relationship between social anxiety and social
      functioning. CONCLUSIONS: To date, the eidence concerning the comorbidity of
      social anxiety disorder and CHR in adolescents and young adults is not sufficient
      to provide clear guidelines for clinical practice. Future longitudinal studies on
      larger samples of the CHR adolescents and young adults are required to examine
      the relationship between social anxiety disorder and the presence of attenuated
      psychotic symptomatology.

PMID- 29019917
TI  - The Prevalence and Characteristics of E-Cigarette Users in the U.S.
AB  - Studies have examined the characteristics of individuals who use e-cigarettes,
      including sociodemographic and smoking characteristics, and the relationship of e
      cigarette use to tobacco control policies. While most studies consider a subset
      of these characteristics with weak measures of regular e-cigarette use, this
      study uses a large, recent U.S. survey to simultaneously consider the association
      of each of these factors with different use measures. Data from the May 2014
      Tobacco Use Supplement-Current Population Survey is supplemented with information
      on tobacco control policies. The prevalence of ever, current (at least 1 of the
      last 30 days), and regular (at least 20 of the last 30 days) e-cigarette use were
      7.7%, 2.1% and 0.9%, implying that 27.0% of ever users were current users of
      which 45.3% were regular users. E-cigarette use varied by socio-demographic
      characteristics and by smoking status, and depended on the measure of use
      adopted. However, regardless of measures, e-cigarette use was higher among those
      smokers who smoked more cigarettes. The association with policies was generally
      weak, but we found more regular use by smokers in low tax and low tobacco control
      spending states. The results indicate that the user characteristics differ
      depending on the e-cigarette use measure. The measure of use should be carefully
      considered in analyzing how e-cigarette use affects cigarette use.

PMID- 29019918
TI  - Protein Misfolding and Aggregation as a Therapeutic Target for Polyglutamine
      Diseases.
AB  - The polyglutamine (polyQ) diseases, such as Huntington's disease and several
      types of spinocerebellar ataxias, are a group of inherited neurodegenerative
      diseases that are caused by an abnormal expansion of the polyQ tract in disease
      causative proteins. Proteins with an abnormally expanded polyQ stretch undergo a
      conformational transition to beta-sheet rich structure, which assemble into
      insoluble aggregates with beta-sheet rich amyloid fibrillar structures and
      accumulate as inclusion bodies in neurons, eventually leading to
      neurodegeneration. Since misfolding and aggregation of the expanded polyQ
      proteins are the most upstream event in the most common pathogenic cascade of the
      polyQ diseases, they are proposed to be one of the most ideal targets for
      development of disease-modifying therapies for polyQ diseases. In this review, we
      summarize the current understanding of the molecular pathogenic mechanisms of the
      polyQ diseases, and introduce therapeutic approaches targeting misfolding and
      aggregation of the expanded polyQ proteins, which are not only effective on a
      wide spectrum of polyQ diseases, but also broadly correct the functional
      abnormalities of multiple downstream cellular processes affected in the
      aggregation process of polyQ proteins. We hope that in the near future, effective
      therapies are developed, to bring hope to many patients suffering from currently
      intractable polyQ diseases.

PMID- 29019920
TI  - Pratol, an O-Methylated Flavone, Induces Melanogenesis in B16F10 Melanoma Cells
      via p-p38 and p-JNK Upregulation.
AB  - Tyrosinase is the rate-limiting enzyme critical for melanin synthesis. It
      controls pigmentation in the skin. Activation of tyrosinase is currently the most
      common approach in the development of tanning and haircare products. Pratol is a
      7-hydroxy-4-methoxyflavone found in Trifoliumpratense. In this study, we
      investigated the effects of pratol on melanogenesis. We also studied the
      mechanism of action of pratol in B16F10 mouse melanoma cells. The cells were
      treated with various concentrations (6.25, 12.5, 25, and 50 MUM) of pratol to
      observe its effects. The results showed that pratol significantly increased
      melanin content and tyrosinase activity in the cells without being cytotoxic. In
      addition, pratol strongly increased the expression of tyrosinase and tyrosinase
      related protein-1 and 2 by enhancing the expression of microphthalmia-associated
      transcription factor. Furthermore, pratol stimulated melanogenesis via the
      phosphorylation of p38, c-Jun N-terminal kinases (JNK), and extracellular signal
      regulated kinase (ERK). The findings from an assay searching for the inhibitor
      revealed that SB203580 (a specific p38 inhibitor) or SP600125 (a p-JNK inhibitor)
      attenuated pratol-induced cellular tyrosinase activity whereas PD98059 (an ERK
      inhibitor) did not. Additionally, pratol interfered with the phosphorylation of p
      AKT. We also found that pratol-induced melanogenesis was reversed by H89, which
      is a specific protein kinase A inhibitor. The results suggest that, owing to its
      multi-functional properties, pratol may be a potential tanning agent or a
      therapeutic agent for hair depigmentation in the cosmetic industry.

PMID- 29019921
TI  - Persistence of Norovirus GII Genome in Drinking Water and Wastewater at Different
      Temperatures.
AB  - Human norovirus (NoV) causes waterborne outbreaks worldwide suggesting their
      ability to persist and survive for extended periods in the environment. The
      objective of this study was to determine the persistence of the NoV GII genome in
      drinking water and wastewater at three different temperatures (3  degrees C, 21 
      degrees C, and 36  degrees C). The persistence of two NoV GII inoculums
      (extracted from stool) and an indigenous NoV GII were studied. The samples were
      collected for up to one year from drinking water and for up to 140 days from
      wastewater. Molecular methods (RT-qPCR) were used to assess the decay of the NoV
      genome. Decay rate coefficients were determined from the fitted decay curves
      using log-linear and/or non-linear model equations. Results showed significant
      differences in the decay kinetics of NoV genome between the temperatures,
      matrices, and virus strains. The persistence of NoV was higher in drinking water
      compared to wastewater, and the cold temperature assisted persistence at both
      matrices. Differences between the persistence of NoV strains were also evident
      and, particularly, indigenous NoVs persisted better than spiked NoVs in
      wastewater. The decay constants obtained in this study can be utilized to assess
      the fate of the NoV genome in different water environments.

PMID- 29019919
TI  - Proteogenomics in Aid of Host-Pathogen Interaction Studies: A Bacterial
      Perspective.
AB  - By providing useful tools to study host-pathogen interactions, next-generation
      omics has recently enabled the study of gene expression changes in both pathogen
      and infected host simultaneously. However, since great discriminative power is
      required to study pathogen and host simultaneously throughout the infection
      process, the depth of quantitative gene expression profiling has proven to be
      unsatisfactory when focusing on bacterial pathogens, thus preferentially
      requiring specific strategies or the development of novel methodologies based on
      complementary omics approaches. In this review, we focus on the difficulties
      encountered when making use of proteogenomics approaches to study bacterial
      pathogenesis. In addition, we review different omics strategies (i.e.,
      transcriptomics, proteomics and secretomics) and their applications for studying
      interactions of pathogens with their host.

PMID- 29019922
TI  - Effect of Silicate Slag Application on Wheat Grown Under Two Nitrogen Rates.
AB  - Field studies were established on the alluvial floodplain soils in Louisiana,
      from 2013 to 2015, to evaluate the effect of silicate slag applications on
      productivity of wheat (Triticum aestivum), under sufficient and high nitrogen (N)
      application rates. Treatments were arranged in a randomized complete block
      design, with four replications consisting of twelve treatments: a factorial
      combination of two N (101 and 145 kg N ha-1) and five silicate slag rates (0, 1,
      2, 4.5, and 9 Mg ha-1), and two control plots (with and without lime). Nitrogen
      had a greater impact on wheat productivity than silicate slag application. Wheat
      grain yield reached over 7000 kg ha-1 with applications of 145 kg N, and 9 Mg
      silicate slag per ha for soil having Si level <20 mg kg-1. Yield increases due to
      N or Si were attributed to the increase in number of spike m-2 and grain number
      spike-1. Silicate slag application effectively raised soil pH, and availability
      of several plant-essential nutrients, including plant-available N (nitrate, NO3
      ), demonstrating the benefits of slag application are beyond increasing plant
      available Si. The benefits of silicate slag application were clearly observed in
      wheat supplied with high N, and on soil with low plant-available Si.

PMID- 29019923
TI  - The Attitude of Medical and Pharmacy Students towards Research Activities: A
      Multicenter Approach.
AB  - Aim: To assess the attitude of medical and pharmacy students in Asian and African
      universities towards scholarly research activities. Methods: An anonymous, cross
      sectional, self-reported online survey questionnaire was administered to medical
      and pharmacy students studying in various Asian and African universities through
      social media between May and July 2016. A 68-item close-ended questionnaire
      consisting of Likert-scale options assessed the students' research-specific
      experiences, and their attitudes towards scholarly research publications.
      Results: A total of 512 questionnaires were completed, with a response rate of
      92% from Asia and 94% from Africa. More pharmacy students (70.8%) participated
      than medical students (29.2%). Overall 52.2% of the pharmacy students and 40% of
      medical students believed that research activities provided a means of gaining
      respect from their faculty members. Lack of encouragement, paucity of time, gaps
      in research activities and practices, and lack of research funding were some of
      the most common barriers acknowledged by the students. A nonparametric Mann
      Whitney test showed that a statistically significant difference was observed, in
      that more than 80% of the pharmacy students viewed scientific writing and
      research activities as valuable experiences (p = 0.001) and would like to involve
      their co-students in scholarly research activities (p = 0.002); whereas the
      majority of the medical students desired to be involved more in scholarly
      research publications (p = 0.033). Conclusion: Pharmacy students had good
      attitudes towards research activities and a higher number of medical students
      desired to be involved more in research publications. Faculties may consider
      taking special research initiatives to address the barriers and improve the
      involvement of medical and pharmacy students in scholarly research activities.

PMID- 29019924
TI  - Impact of Temperature and UV Irradiation on Dynamics of NO2 Sensors Based on ZnO
      Nanostructures.
AB  - The main object of this study is the improvement of the dynamics of NO2 sensors
      based on ZnO nanostructures. Investigations presented in this paper showed that
      the combination of temperature and ultraviolet (UV) activation of the sensors can
      significantly decrease the sensor response and regeneration times. In comparison
      with the single activation method (elevated temperature or UV), these times for 1
      ppm of NO2 decreased from about 10 min (or more) to less than 40 s. In addition,
      at the optimal conditions (200  degrees C and UV), sensors were very stable, were
      fully scalable (in the range on NO2 concentration of 1-20 ppm) and baseline drift
      was significantly reduced. Furthermore, in this paper, extensive studies of the
      influence of temperature and carrier gas (nitrogen and air) on NO2 sensing
      properties of the ZnO nanostructures were conducted. The NO2 sensing mechanisms
      of the sensors operating at elevated temperatures and under UV irradiation were
      also discussed. Our study showed that sensor responses to NO2 and
      response/regeneration times are comparable from sensor to sensor in air and
      nitrogen conditions, which suggests that the proposed simple technology connected
      with well-chosen operation conditions is repeatable. The estimated limit of
      detection of the sensors is within the level of ~800 ppb in nitrogen and ~700 ppb
      in air.

PMID- 29019925
TI  - Three-Dimensional Porous Nitrogen-Doped NiO Nanostructures as Highly Sensitive
      NO2 Sensors.
AB  - Nickel oxide has been widely used in chemical sensing applications, because it
      has an excellent p-type semiconducting property with high chemical stability.
      Here, we present a novel technique of fabricating three-dimensional porous
      nitrogen-doped nickel oxide nanosheets as a highly sensitive NO2 sensor. The
      elaborate nanostructure was prepared by a simple and effective hydrothermal
      synthesis method. Subsequently, nitrogen doping was achieved by thermal treatment
      with ammonia gas. When the p-type dopant, i.e., nitrogen atoms, was introduced in
      the three-dimensional nanostructures, the nickel-oxide-nanosheet-based sensor
      showed considerable NO2 sensing ability with two-fold higher responsivity and
      sensitivity compared to non-doped nickel-oxide-based sensors.

PMID- 29019926
TI  - The Effects of Acid Etching on the Nanomorphological Surface Characteristics and
      Activation Energy of Titanium Medical Materials.
AB  - The purpose of this study was to characterize the etching mechanism, namely, the
      etching rate and the activation energy, of a titanium dental implant in
      concentrated acid and to construct the relation between the activation energy and
      the nanoscale surface topographies. A commercially-pure titanium (CP Ti) and Ti
      6Al-4V ELI surface were tested by shot blasting (pressure, grain size, blasting
      distance, blasting angle, and time) and acid etching to study its topographical,
      weight loss, surface roughness, and activation energy. An Arrhenius equation was
      applied to derive the activation energy for the dissolution of CP Ti/Ti-6Al-4V
      ELI in sulfuric acid (H2SO4) and hydrochloric acid (HCl) at different
      temperatures. In addition, white-light interferometry was applied to measure the
      surface nanomorphology of the implant to obtain 2D or 3D roughness parameters
      (Sa, Sq, and St). The nanopore size that formed after etching was approximately
      100-500 nm. The surface roughness of CP Ti and Ti-6Al-4V ELI decreased as the
      activation energy decreased but weight loss increased. Ti-6Al-4V ELI has a higher
      level of activation energy than Ti in HCl, which results in lower surface
      roughness after acid etching. This study also indicates that etching using a
      concentrated hydrochloric acid provided superior surface modification effects in
      titanium compared with H2SO4.

PMID- 29019928
TI  - The Abundance of Toxic Genotypes Is a Key Contributor to Anatoxin Variability in
      Phormidium-Dominated Benthic Mats.
AB  - The prevalence of benthic proliferations of the anatoxin-producing cyanobacterium
      Phormidium are increasing in cobble-bed rivers worldwide. Studies to date have
      shown high spatial and temporal variability in anatoxin concentrations among
      mats. In this study we determined anatoxin quotas (toxins per cell) in field
      samples and compared these results to the conventionally-used concentrations
      (assessed per dry weight of mat). Three mats were selected at sites in two rivers
      and were sampled every 2-3 h for 24-26 h. The samples were lyophilized and ground
      to a fine homogenous powder. Two aliquots of known weights were analyzed for
      anatoxin congeners using liquid chromatography-mass spectrometry, or digital
      droplet PCR with Phormidium-specific anaC primers to measure absolute quantities
      of gene copies. Anatoxin concentrations in the mats varied 59- and 303-fold in
      the two rivers over the study periods. A similar pattern was observed among gene
      copies (53- and 2828-fold). When converted to anatoxin quotas there was markedly
      less variability (42- and 16-fold), but significantly higher anatoxin quotas were
      observed in mats from the second river (p < 0.001, Student's t-test). There were
      no obvious temporal patterns with high and low anatoxin concentrations or quotas
      measured at each sampling time and across the study period. These results
      demonstrate that variability in anatoxin concentrations among mats is primarily
      due to the abundance of toxic genotypes. No consistent modulation in anatoxin
      production was observed during the study, although significant differences in
      anatoxin quotas among rivers suggest that site-specific physiochemical or
      biological factors may influence anatoxin production.

PMID- 29019927
TI  - Mediterranean Diet Adherence and Genetic Background Roles within a Web-Based
      Nutritional Intervention: The Food4Me Study.
AB  - Mediterranean Diet (MedDiet) adherence has been proven to produce numerous health
      benefits. In addition, nutrigenetic studies have explained some individual
      variations in the response to specific dietary patterns. The present research
      aimed to explore associations and potential interactions between MedDiet
      adherence and genetic background throughout the Food4Me web-based nutritional
      intervention. Dietary, anthropometrical and biochemical data from volunteers of
      the Food4Me study were collected at baseline and after 6 months. Several genetic
      variants related to metabolic risk features were also analysed. A Genetic Risk
      Score (GRS) was derived from risk alleles and a Mediterranean Diet Score (MDS),
      based on validated food intake data, was estimated. At baseline, there were no
      interactions between GRS and MDS categories for metabolic traits. Linear mixed
      model repeated measures analyses showed a significantly greater decrease in total
      cholesterol in participants with a low GRS after a 6-month period, compared to
      those with a high GRS. Meanwhile, a high baseline MDS was associated with greater
      decreases in Body Mass Index (BMI), waist circumference and glucose. There also
      was a significant interaction between GRS and the MedDiet after the follow-up
      period. Among subjects with a high GRS, those with a high MDS evidenced a highly
      significant reduction in total carotenoids, while among those with a low GRS,
      there was no difference associated with MDS levels. These results suggest that a
      higher MedDiet adherence induces beneficial effects on metabolic outcomes, which
      can be affected by the genetic background in some specific markers.

PMID- 29019930
TI  - Biological Evaluation and Molecular Docking of Protocatechuic Acid from Hibiscus
      sabdariffa L. as a Potent Urease Inhibitor by an ESI-MS Based Method.
AB  - Studies on enzyme inhibition remain a crucial area in drug discovery since these
      studies have led to the discoveries of new lead compounds useful in the treatment
      of several diseases. In this study, protocatechuic acid (PCA), an active compound
      from Hibiscus sabdariffa L. has been evaluated for its inhibitory properties
      against jack bean urease (JBU) as well as its possible toxic effect on human
      gastric epithelial cells (GES-1). Anti-urease activity was evaluated by an
      Electrospray Ionization-Mass Spectrometry (ESI-MS) based method, while
      cytotoxicity was assayed by the MTT method. PCA exerted notable anti-JBU activity
      compared with that of acetohydroxamic acid (AHA), with IC50 values of 1.7 and 3.2
      uM, respectively. PCA did not show any significant cytotoxic effect on (GES-1)
      cells at concentrations ranging from 1.12 to 3.12 uM. Molecular docking study
      revealed high spontaneous binding ability of PCA to the active site of urease.
      Additionally, the anti-urease activity was found to be related to the presence of
      hydroxyl moieties of PCA. This study presents PCA as a natural urease inhibitor,
      which could be used safely in the treatment of diseases caused by urease
      producing bacteria.

PMID- 29019931
TI  - Targeted Next-Generation Sequencing Identification of Mutations in Disease
      Resistance Gene Analogs (RGAs) in Wild and Cultivated Beets.
AB  - Resistance gene analogs (RGAs) were searched bioinformatically in the sugar beet
      (Beta vulgaris L.) genome as potential candidates for improving resistance
      against different diseases. In the present study, Ion Torrent sequencing
      technology was used to identify mutations in 21 RGAs. The DNA samples of ninety
      six individuals from six sea beets (Beta vulgaris L. subsp. maritima) and six
      sugar beet pollinators (eight individuals each) were used for the discovery of
      single-nucleotide polymorphisms (SNPs). Target amplicons of about 200 bp in
      length were designed with the Ion AmpliSeq Designer system in order to cover the
      DNA sequences of the RGAs. The number of SNPs ranged from 0 in four individuals
      to 278 in the pollinator R740 (which is resistant to rhizomania infection). Among
      different groups of beets, cytoplasmic male sterile lines had the highest number
      of SNPs (132) whereas the lowest number of SNPs belonged to O-types (95). The
      principal coordinates analysis (PCoA) showed that the polymorphisms inside the
      gene Bv8_184910_pkon (including the CCCTCC sequence) can effectively
      differentiate wild from cultivated beets, pointing at a possible mutation
      associated to rhizomania resistance that originated directly from cultivated
      beets. This is unlike other resistance sources that are introgressed from wild
      beets. This gene belongs to the receptor-like kinase (RLK) class of RGAs, and is
      associated to a hypothetical protein. In conclusion, this first report of using
      Ion Torrent sequencing technology in beet germplasm suggests that the identified
      sequence CCCTCC can be used in marker-assisted programs to differentiate wild
      from domestic beets and to identify other unknown disease resistance genes in
      beet.

PMID- 29019929
TI  - Chemical and Biological Research on Herbal Medicines Rich in Xanthones.
AB  - Xanthones, as some of the most active components and widely distributed in
      various herb medicines, have drawn more and more attention in recent years. So
      far, 168 species of herbal plants belong to 58 genera, 24 families have been
      reported to contain xanthones. Among them, Calophyllum, Cratoxylum, Cudrania,
      Garcinia, Gentiana, Hypericum and Swertia genera are plant resources with great
      development prospect. This paper summarizes the plant resources, bioactivity and
      the structure-activity relationships (SARs) of xanthones from references
      published over the last few decades, which may be useful for new drug research
      and development on xanthones.

PMID- 29019932
TI  - ASIC1a Promotes Acid-Induced Autophagy in Rat Articular Chondrocytes through the
      AMPK/FoxO3a Pathway.
AB  - Acid-sensing ion channel 1a (ASIC1a) is a member of the extracellular H+
      activated cation channels family. Our previous studies suggested that ASIC1a
      contributed to acid-induced rat articular chondrocytes autophagy. However, its
      potential mechanisms remain unclear. The present study demonstrated the effect of
      ASIC1a on rat articular chondrocytes autophagy and explored the underlying
      molecular mechanisms. The results demonstrated that ASIC1a contributed to acid
      induced autophagy in rat articular chondrocytes, and which was associated with an
      increase in (Ca2+)i, as indicated that acid-induced increases in mRNA and protein
      expression of LC3B-II and other autophagy-related markers were inhibited by
      ASIC1a-specific blocker, PcTx1 and calcium chelating agent, BAPTA-AM.
      Furthermore, the results showed that extracellular acid increased level of
      Forkhead box O (FoxO) 3a, but was reversed by inhibition of ASIC1a and Ca2+
      influx. Moreover, gene ablation of FoxO3a prevented acid-induced increases in
      mRNA and protein expression of LC3B-II, Beclin1 and the formation of
      autophagosome. Finally, it also showed that ASIC1a activated adenine nucleotide
      (AMP)-activated protein kinase (AMPK). In addition, suppression of AMPK by
      Compound C and its small interfering RNA (siRNA) prevented acid-induced
      upregulation of total and nuclear FoxO3a and increases in mRNA and protein
      expression of LC3B-II, Beclin1, and ATG5. Taken together, these findings
      suggested that AMPK/FoxO3a axis plays an important role in ASIC1a-mediated
      autophagy in rat articular chondrocytes, which may provide novel mechanistic
      insight into ASIC1a effects on autophagy.

PMID- 29019934
TI  - A Massively Parallel Sequence Similarity Search for Metagenomic Sequencing Data.
AB  - Sequence similarity searches have been widely used in the analyses of metagenomic
      sequencing data. Finding homologous sequences in a reference database enables the
      estimation of taxonomic and functional characteristics of each query sequence.
      Because current metagenomic sequencing data consist of a large number of
      nucleotide sequences, the time required for sequence similarity searches account
      for a large proportion of the total time. This time-consuming step makes it
      difficult to perform large-scale analyses. To analyze large-scale metagenomic
      data, such as those found in the human oral microbiome, we developed GHOST-MP
      (Genome-wide HOmology Search Tool on Massively Parallel system), a parallel
      sequence similarity search tool for massively parallel computing systems. This
      tool uses a fast search algorithm based on suffix arrays of query and database
      sequences and a hierarchical parallel search to accelerate the large-scale
      sequence similarity search of metagenomic sequencing data. The parallel computing
      efficiency and the search speed of this tool were evaluated. GHOST-MP was shown
      to be scalable over 10,000 CPU (Central Processing Unit) cores, and achieved over
      80-fold acceleration compared with mpiBLAST using the same computational
      resources. We applied this tool to human oral metagenomic data, and the results
      indicate that the oral cavity, the oral vestibule, and plaque have different
      characteristics based on the functional gene category.

PMID- 29019933
TI  - Adsorption Removal of 17beta-Estradiol from Water by Rice Straw-Derived Biochar
      with Special Attention to Pyrolysis Temperature and Background Chemistry.
AB  - Rice straw biochar that produced at three pyrolysis temperatures (400, 500 and
      600  degrees C) were used to investigate the adsorption properties of 17beta
      estradiol (E2). The biochar samples were characterized by scanning electron
      microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), elemental
      analysis and BET surface area measurements. The influences of pyrolysis
      temperature, E2 concentration, pH, ionic strength, background electrolyte and
      humic acid were studied. Kinetic and isotherm results illustrated that the
      adsorption process could be well described by pseudo-second-order and Freundlich
      models. Experimental results showed that ionic strength had less influence on the
      adsorption of E2 by 500 and 600  degrees C rice straw biochar. Further,
      multivalent ions had positive impact on E2 removal than monovalent ions and the
      influence of the pyrolysis temperature was unremarkable when background
      electrolyte existed in solutions. The adsorption capacity of E2 decreased with
      the pH ranged from 3.0 to 12.0 and the humic acid concentration from 2 to 10 mg L
      1. Electrostatic attractions and pi-pi interaction were involved in the
      adsorption mechanisms. Compared to low-temperature biochar, high-temperature
      biochar exhibited a better adsorption capacity for E2 in aqueous solution,
      indicated it had a greater potential for E2 pollution control.

PMID- 29019936
TI  - Image-Based Analysis to Dissect Vertical Distribution and Horizontal Asymmetry of
      Conspecific Root System Interactions in Response to Planting Densities, Nutrients
      and Root Exudates in Arabidopsis thaliana.
AB  - Intraspecific competition is an important plant interaction that has been studied
      extensively aboveground, but less so belowground, due to the difficulties in
      accessing the root system experimentally. Recent in vivo and in situ automatic
      imaging advances help understand root system architecture. In this study, a
      portable imaging platform and a scalable transplant technique were applied to
      test intraspecific competition in Arabidopsis thaliana. A single green
      fluorescent protein labeled plant was placed in the center of a grid of different
      planting densities of neighboring unlabeled plants or empty spaces, into which
      different treatments were made to the media. The root system of the central plant
      showed changes in the vertical distribution with increasing neighbor density,
      becoming more positively kurtotic, and developing an increasing negative skew
      with time. Horizontal root distribution was initially asymmetric, but became more
      evenly circular with time, and mean direction was not affected by the presence of
      adjacent empty spaces as initially hypothesized. To date, this is the first study
      to analyze the patterns of both vertical and horizontal growth in conspecific
      root systems. We present a portable imaging platform with simplicity,
      accessibility, and scalability, to capture the dynamic interactions of plant root
      systems.

PMID- 29019937
TI  - A Critical Appraisal of Extracorporeal Photopheresis as a Treatment Modality for
      Acute and Chronic Graft-Versus-Host Disease.
AB  - Although significant advances have been made in the biologic understanding of
      graft-versus-host disease (GVHD) and its treatment options, GVHD remains the
      single most challenging obstacle to the success of allogeneic hematopoietic cell
      transplantation (HCT) due to high risk of disabling morbidity and mortality.
      Extracorporeal photopheresis (ECP) has promising effects in controlling steroid
      refractory GVHD, both acute and chronic, and it has been studied extensively. Its
      putative immunomodulatory mechanisms, while not immunosuppressive, position ECP
      as an attractive treatment strategy for GVHD patients who are already receiving
      global immunosuppression. However, ECP is relatively underutilized due in part to
      limited access and time commitment. Here, we review the recent findings on the
      ECP efficacy in both acute and chronic GVHD, primarily for steroid-refractory
      status, and we critically appraise its benefits. We also explore salient
      considerations on the optimal use of ECP in the treatment of refractory GVHD.

PMID- 29019935
TI  - Cardiotoxic Effects of Short-Term Doxorubicin Administration: Involvement of
      Connexin 43 in Calcium Impairment.
AB  - The use of Doxorubicin (DOXO), a potent antineoplastic agent, is limited by the
      development of cardiotoxicity. DOXO-induced cardiotoxicity is multifactorial,
      although alterations in calcium homeostasis, seem to be involved. Since even the
      Connexin43 (Cx43) plays a pivotal role in these two phenomena, in this study we
      have analyzed the effects of DOXO on Cx43 expression and localization. Damage
      caused by anthracyclines on cardiomyocytes is immediate after each injection, in
      the present study we used a short-term model of DOXO-induced cardiomyopathy.
      C57BL/6j female mice were randomly divided in groups and injected with DOXO (2 or
      10 mg/kg i.p.) for 1-3 or 7 days once every other day. Cardiac function was
      assessed by Echocardiography. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCAII)
      and phospholamban (PLB) expression were assessed by Western blot analysis,
      intracellular [Ca2+] were detected spectrofluorometrically by means of Fura-2
      pentakis (acetoxymethyl) ester (FURA-2AM), and Cx43 and pCx43 expression and
      localization was analyzed by Western blot and confirmed by immunofluorescence
      analysis. DOXO induces impairment in Ca2+ homeostasis, already evident after a
      single administration, and affects Cx43 expression and localization. Our data
      suggest that DOXO-induced alterations in Ca2+ homeostasis causes in the cells the
      induction of compensatory mechanisms until a certain threshold, above which
      cardiac injury is triggered.

PMID- 29019939
TI  - Creating Affording Situations: Coaching through Animate Objects.
AB  - We explore the ways in which animate objects can be used to cue actions as part
      of coaching in Activities of Daily Living (ADL). In this case, changing the
      appearance or behavior of a physical object is intended to cue actions which are
      appropriate for a given context. The context is defined by the intention of the
      users, the state of the objects and the tasks for which these objects can be
      used. We present initial design prototypes and simple user trials which explore
      the impact of different cues on activity. It is shown that raising the handle of
      a jug, for example, not only cues the act of picking up the jug but also
      encourages use of the hand adjacent to the handle; that combinations of lights
      (on the objects) and auditory cues influence activity through reducing
      uncertainty; and that cueing can challenge pre-learned action sequences. We
      interpret these results in terms of the idea that the animate objects can be used
      to create affording situations, and discuss implications of this work to support
      relearning of ADL following brain damage or injury, such as might arise following
      a stroke.

PMID- 29019938
TI  - DMRTC2, PAX7, BRACHYURY/T and TERT Are Implicated in Male Germ Cell Development
      Following Curative Hormone Treatment for Cryptorchidism-Induced Infertility.
AB  - Defective mini-puberty results in insufficient testosterone secretion that
      impairs the differentiation of gonocytes into dark-type (Ad) spermatogonia. The
      differentiation of gonocytes into Ad spermatogonia can be induced by
      administration of the gonadotropin-releasing hormone agonist, GnRHa (Buserelin,
      INN)). Nothing is known about the mechanism that underlies successful GnRHa
      treatment in the germ cells. Using RNA-sequencing of testicular biopsies, we
      recently examined RNA profiles of testes with and without GnRHa treatment. Here,
      we focused on the expression patterns of known gene markers for gonocytes and
      spermatogonia, and found that DMRTC2, PAX7, BRACHYURY/T, and TERT were associated
      with defective mini-puberty and were responsive to GnRHa. These results indicate
      novel testosterone-dependent genes and provide valuable insight into the
      transcriptional response to both defective mini-puberty and curative GnRHa
      treatment, which prevents infertility in man with one or both undescended
      (cryptorchid) testes.

PMID- 29019940
TI  - Effects of Extremely Low Frequency Electromagnetic Fields on Melanogenesis
      through p-ERK and p-SAPK/JNK Pathways in Human Melanocytes.
AB  - This study evaluated frequency-dependent effects of extremely low frequency
      electromagnetic fields (ELF-EMFs) on melanogenesis by melanocytes in vitro.
      Melanocytes were exposed to 2 mT EMFs at 30-75 Hz for 3 days before melanogenesis
      was examined. Exposure to ELF-EMFs at 50 and 60 Hz induced melanogenic maturation
      without cell damage, without changing cell proliferation and mitochondrial
      activity. Melanin content and tyrosinase activity of cells exposed to 50 Hz were
      higher than in controls, and mRNA expression of tyrosinase-related protein-2 was
      elevated relative to controls at 50 Hz. Phosphorylated cyclic adenosine
      monophosphate response element-binding protein (p-CREB) levels were higher than
      controls in cells exposed to ELF-EMFs at 50-75 Hz. Immunohistochemical staining
      showed that melanocyte-specific markers (HMB45, Melan-A) were strongly expressed
      in cells exposed to EMFs at 50 and 60 Hz compared to controls. Thus, exposure to
      ELF-EMFs at 50 Hz could stimulate melanogenesis in melanocytes, through
      activation of p-CREB and p-p38 and inhibition of phosphorylated extracellular
      signal-regulated protein kinase and phosphorylated stress-activated protein
      kinase/c-Jun N-terminal kinase. The results may form the basis of an appropriate
      anti-gray hair treatment or be applied in a therapeutic device for inducing
      repigmentation in the skin of vitiligo patients.

PMID- 29019943
TI  - Some Hardware and Instrumentation Aspects of the Development of an Automation
      System for Jar Tests in Drinking Water Treatment.
AB  - The so-called Jar Test (JT) plays a vital role in the drinking water and
      wastewater treatments for establishing the dosage of flocculants and coagulant.
      This test is a well-proved laboratory instrumental procedure performed by trained
      personnel. In this work, a completely novel system for the automation and
      monitoring of a JT devoted to drinking water treatment is presented. It has been
      implemented using an industrial programmable controller and sensors and
      instruments specifically selected for this purpose. Once the parameters of the
      test have been entered, the stages that compose the JT (stirring, coagulant
      addition, etc.) are sequentially performed without human intervention. Moreover,
      all the involved measurements from sensors are collected and made accessible for
      continuous monitoring of the process. By means of the proposed system, the JT
      procedure is conducted fully automatically and can be locally and remotely
      monitored in real-time. Furthermore, the developed system constitutes a portable
      laboratory that offers advantageous features like scalability and
      transportability. The proposed system is described focusing on hardware and
      instrumentation aspects, and successful results are reported.

PMID- 29019942
TI  - NADPH Oxidase-Related Pathophysiology in Experimental Models of Stroke.
AB  - Several experimental studies have indicated that nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidases (Nox) exert detrimental effects on
      ischemic brain tissue; Nox-knockout mice generally exhibit resistance to damage
      due to experimental stroke following middle cerebral artery occlusion (MCAO).
      Furthermore, our previous MCAO study indicated that infarct size and blood-brain
      barrier breakdown are enhanced in mice with pericyte-specific overexpression of
      Nox4, relative to levels observed in controls. However, it remains unclear
      whether Nox affects the stroke outcome directly by increasing oxidative stress at
      the site of ischemia, or indirectly by modifying physiological variables such as
      blood pressure or cerebral blood flow (CBF). Because of technical problems in the
      measurement of physiological variables and CBF, it is often difficult to address
      this issue in mouse models due to their small body size; in our previous study,
      we examined the effects of Nox activity on focal ischemic injury in a novel
      congenic rat strain: stroke-prone spontaneously hypertensive rats with loss-of
      function in Nox. In this review, we summarize the current literature regarding
      the role of Nox in focal ischemic injury and discuss critical issues that should
      be considered when investigating Nox-related pathophysiology in animal models of
      stroke.

PMID- 29019941
TI  - The Contribution of Adipose Tissue-Derived Mesenchymal Stem Cells and Platelet
      Rich Plasma to the Treatment of Chronic Equine Laminitis: A Proof of Concept.
AB  - Laminitis, a highly debilitating disease of the foot in ungulates, is
      characterized by pathological changes of the complex lamellar structures that
      maintain the appendicular skeleton within the hoof. Laminitis is a multifactorial
      disease that involves perturbation of the vascular, hematological, and
      inflammatory homeostasis of the foot. Interestingly, the pathogenesis of the
      disease resembles what is observed in metabolic syndromes and sepsis-induced
      organ failure in humans and animals. We hypothesized that local administration of
      mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) might contribute to
      establishing an anti-inflammatory and pro-angiogenic environment, and could
      stimulate the injured tissue in order to restore its functional integrity.
      According to this assumption, an experimental protocol based on the local
      intravenous administration of adipose tissue-derived MSCs (aMSCs) in combination
      with PRP was developed for the treatment of horses affected by chronic laminitis.
      Nine horses with severely compromised venograms (showing grade III and IV
      laminitis) that had been unsuccessfully treated with conventional therapies were
      enrolled. aMSCs and PRP (15 * 106 cells resuspended in 15 mL of PRP) were
      injected into the lateral or medial digital vein three times, at one-month
      intervals. The first administration was performed with allogeneic aMSCs, while
      for the following administrations, autologous aMSCs were used. There was no
      adverse short-term reaction to the intravenous injection of aMSCs. In the long
      term, venograms outlined, in all subjects, a progressive amelioration of the
      vascularization of the foot. An improvement in the structure and function of the
      hoof was also observed. No adverse events were reported during the follow-up, and
      the horses returned to a comfortable quality of life. Although the number of
      animals enrolled in the study is limited, both clinical observations and
      venography demonstrated an enhancement in the condition of all horses, suggesting
      that the regenerative therapies in chronic laminitis could be useful, and are
      worthy of further investigation.

PMID- 29019944
TI  - Variation and Distribution of L-A Helper Totiviruses in Saccharomyces sensu
      stricto Yeasts Producing Different Killer Toxins.
AB  - Yeasts within the Saccharomyces sensu stricto cluster can produce different
      killer toxins. Each toxin is encoded by a medium size (1.5-2.4 Kb) M dsRNA virus,
      maintained by a larger helper virus generally called L-A (4.6 Kb). Different
      types of L-A are found associated to specific Ms: L-A in K1 strains and L-A-2 in
      K2 strains. Here, we extend the analysis of L-A helper viruses to yeasts other
      than S. cerevisiae, namely S. paradoxus, S. uvarum and S. kudriavzevii. Our
      sequencing data from nine new L-A variants confirm the specific association of
      each toxin-producing M and its helper virus, suggesting co-evolution. Their
      nucleotide sequences vary from 10% to 30% and the variation seems to depend on
      the geographical location of the hosts, suggesting cross-species transmission
      between species in the same habitat. Finally, we transferred by genetic methods
      different killer viruses from S. paradoxus into S. cerevisiae or viruses from S.
      cerevisiae into S. uvarum or S. kudriavzevii. In the foster hosts, we observed no
      impairment for their stable transmission and maintenance, indicating that the
      requirements for virus amplification in these species are essentially the same.
      We also characterized new killer toxins from S. paradoxus and constructed
      "superkiller" strains expressing them.

PMID- 29019946
TI  - Review of Ecologically-Based Pest Management in California Vineyards.
AB  - Grape growers in California utilize a variety of biological, cultural, and
      chemical approaches for the management of insect and mite pests in vineyards.
      This combination of strategies falls within the integrated pest management (IPM)
      framework, which is considered to be the dominant pest management paradigm in
      vineyards. While the adoption of IPM has led to notable and significant
      reductions in the environmental impacts of grape production, some growers are
      becoming interested in the use of an explicitly non-pesticide approach to pest
      management that is broadly referred to as ecologically-based pest management
      (EBPM). Essentially a subset of IPM strategies, EBPM places strong emphasis on
      practices such as habitat management, natural enemy augmentation and
      conservation, and animal integration. Here, we summarize the range and known
      efficacy of EBPM practices utilized in California vineyards, followed by a
      discussion of research needs and future policy directions. EBPM should in no way
      be seen in opposition, or as an alternative to the IPM framework. Rather, the
      further development of more reliable EBPM practices could contribute to the
      robustness of IPM strategies available to grape growers.

PMID- 29019945
TI  - Micro and Nanostructured Materials for the Development of Optical Fibre Sensors.
AB  - The measurement of chemical and biomedical parameters can take advantage of the
      features exclusively offered by optical fibre: passive nature, electromagnetic
      immunity and chemical stability are some of the most relevant ones. The small
      dimensions of the fibre generally require that the sensing material be loaded
      into a supporting matrix whose morphology is adjusted at a nanometric scale.
      Thanks to the advances in nanotechnology new deposition methods have been
      developed: they allow reagents from different chemical nature to be embedded into
      films with a thickness always below a few microns that also show a relevant
      aspect ratio to ensure a high transduction interface. This review reveals some of
      the main techniques that are currently been employed to develop this kind of
      sensors, describing in detail both the resulting supporting matrices as well as
      the sensing materials used. The main objective is to offer a general view of the
      state of the art to expose the main challenges and chances that this technology
      is facing currently.

PMID- 29019948
TI  - Optimization and Characterization of the Friction Stir Welded Sheets of AA 5754
      H111: Monitoring of the Quality of Joints with Thermographic Techniques.
AB  - Friction Stir Welding (FSW) is a solid-state welding process, based on frictional
      and stirring phenomena, that offers many advantages with respect to the
      traditional welding methods. However, several parameters can affect the quality
      of the produced joints. In this work, an experimental approach has been used for
      studying and optimizing the FSW process, applied on 5754-H111 aluminum plates. In
      particular, the thermal behavior of the material during the process has been
      investigated and two thermal indexes, the maximum temperature and the heating
      rate of the material, correlated to the frictional power input, were investigated
      for different process parameters (the travel and rotation tool speeds)
      configurations. Moreover, other techniques (micrographs, macrographs and
      destructive tensile tests) were carried out for supporting in a quantitative way
      the analysis of the quality of welded joints. The potential of thermographic
      technique has been demonstrated both for monitoring the FSW process and for
      predicting the quality of joints in terms of tensile strength.

PMID- 29019947
TI  - Trends and Comparisons of Utilization of Emergency Departments Due to Traumatic
      or Non-Traumatic Causes among the HIV-Positive Population in Taiwan, 2006-2011.
AB  - It is important that the utilization of emergency departments (EDs) among people
      living with the human immunodeficiency virus (HIV) be epidemiologically evaluated
      in order to assess and improve the HIV care continuum. All participants newly
      diagnosed with HIV in Taiwan registered in the National Health Insurance Database
      from 2000 to 2005 were enrolled in this study and followed-up from 2006 to 2011.
      In total, 3500 participants newly-diagnosed with HIV in 2000-2005 were selected
      as a fixed-cohort population and followed-up from 2006 to 2011. Overall, 704,
      645, 591, 573, 578, and 568 cases made 1322, 1275, 1050, 1061, 1136, and 992 ED
      visits in 2006, 2007, 2008, 2009, 2010 and 2011, respectively, with an average
      number of ED visits ranging from 1.75 to 1.98 per person, accounting for 20.1
      22.6% of the whole HIV-positive population. Fewer ED visits were due to traumatic
      reasons, accounting for 19.6-24.4% of all cases. The incidence of traumatic and
      non-traumatic ED visits among the HIV-positive participants ranged from 7.2-9.3
      and 27.0-33.9 per 100 people, respectively. The average direct medical cost of
      traumatic and non-traumatic ED visits ranged from $89.3-112.0 and $96.6-120.0,
      respectively. In conclusion, a lower incidence of ED visits for all reasons and
      fewer ED visits owing to traumatic causes were observed in the population living
      with HIV in comparison with the general population; however, the direct medical
      cost of each ED visit owing to both traumatic and non-traumatic causes was
      greater among those living with HIV than in the general population.

PMID- 29019949
TI  - Distributed State Estimation Using a Modified Partitioned Moving Horizon Strategy
      for Power Systems.
AB  - In this paper, a distributed state estimation method based on moving horizon
      estimation (MHE) is proposed for the large-scale power system state estimation.
      The proposed method partitions the power systems into several local areas with
      non-overlapping states. Unlike the centralized approach where all measurements
      are sent to a processing center, the proposed method distributes the state
      estimation task to the local processing centers where local measurements are
      collected. Inspired by the partitioned moving horizon estimation (PMHE)
      algorithm, each local area solves a smaller optimization problem to estimate its
      own local states by using local measurements and estimated results from its
      neighboring areas. In contrast with PMHE, the error from the process model is
      ignored in our method. The proposed modified PMHE (mPMHE) approach can also take
      constraints on states into account during the optimization process such that the
      influence of the outliers can be further mitigated. Simulation results on the
      IEEE 14-bus and 118-bus systems verify that our method achieves comparable state
      estimation accuracy but with a significant reduction in the overall computation
      load.

PMID- 29019950
TI  - Computer Vision-Based Structural Displacement Measurement Robust to Light-Induced
      Image Degradation for In-Service Bridges.
AB  - The displacement responses of a civil engineering structure can provide important
      information regarding structural behaviors that help in assessing safety and
      serviceability. A displacement measurement using conventional devices, such as
      the linear variable differential transformer (LVDT), is challenging owing to
      issues related to inconvenient sensor installation that often requires additional
      temporary structures. A promising alternative is offered by computer vision,
      which typically provides a low-cost and non-contact displacement measurement that
      converts the movement of an object, mostly an attached marker, in the captured
      images into structural displacement. However, there is limited research on
      addressing light-induced measurement error caused by the inevitable sunlight in
      field-testing conditions. This study presents a computer vision-based
      displacement measurement approach tailored to a field-testing environment with
      enhanced robustness to strong sunlight. An image-processing algorithm with an
      adaptive region-of-interest (ROI) is proposed to reliably determine a marker's
      location even when the marker is indistinct due to unfavorable light. The
      performance of the proposed system is experimentally validated in both laboratory
      scale and field experiments.

PMID- 29019951
TI  - Chemotherapy-Related Toxicity, Nutritional Status and Quality of Life in
      Precachectic Oncologic Patients with, or without, High Protein Nutritional
      Support. A Prospective, Randomized Study.
AB  - BACKGROUND: Cancer disease is usually associated with impaired nutritional
      status, which is one of the factors contributing to deterioration of the results
      of surgery, chemotherapy or radiotherapy. OBJECTIVES: The aim of the study was to
      determine whether nutritional support with high protein (ONS) in adult oncologic
      patients in the first step of cancer cachexia-asymptomatic precachexia, has an
      influence on the toxicity of systemic therapy. However, secondary endpoints were
      established: to determine whether high protein ONS influences the nutritional
      status, the quality of life, and the performance status. MATERIALS AND METHODS: A
      total of 114 persons aged 40-84 years old with colorectal cancer were examined.
      Based on the randomization, 47 patients were qualified to the interventional
      group (ONS group) and 48 to Control group. To evaluate the nutritional status NRS
      2002 (Nutritional Risk Screening), SGA (Subjective Global Assessment), SCRINIO
      (SCReenIng the Nutritional status In Oncology) Working Group classification, VAS
      (Visual Analog Scale) for appetite was used. FAACT (Functional Assessment of
      Anorexia/Cachexia Therapy) questionnaire was used for assessment of the quality
      of life. The health status of patients was evaluated based on the Karnofsky
      Performance Scale. Anthropometric measurements were done. RESULTS: Severe
      complications of chemotherapy, which caused the end of treatment, a slight
      complication of the gastrointestinal tract such as diarrhea grade 2 according to
      ECOG (Eastern Cooperative Oncology Group) score regardless of the studied group,
      were observed. There were no statistical differences in the number and severity
      of the observed complications, i.e., neutropenia, leucopenia, thrombocytopenia,
      anemia, abdominal pain, nausea and vomiting, and diarrhea. During the follow-up
      the significant changes of SGA, VAS, albumin and prealbumin were observed between
      groups. In the ONS group an improvement in nutritional status was noticed
      (increased appetite VAS, p = 0.05; increased points in SGA, p = 0.015, and
      increased levels of albumin and prealbumin, p = 0.05). In Control group
      nutritional status was stable during observation. The performance status and
      quality of life were stable in both groups. No statistical differences between
      groups (ONS vs. Control) in the numbers for disqualification, resignation, delay
      in treatment, or dose reduction were observed. CONCLUSIONS: Results of the study
      did not indicate that nutritional support in precachectic oncologic patients
      influenced the toxicity of systemic therapy. High protein nutritional support
      improved nutritional status assessed by SGA, VAS for appetite, albumin, and
      prealbumin. The performance status and quality of life were stable throughout the
      observation and were not changed under the supplementation.

PMID- 29019953
TI  - Assessment of Ionospheric Gradient Impacts on Ground-Based Augmentation System
      (GBAS) Data in Guangdong Province, China.
AB  - Ionospheric delay is one of the largest and most variable sources of error for
      Ground-Based Augmentation System (GBAS) users because inospheric activity is
      unpredictable. Under normal conditions, GBAS eliminates ionospheric delays, but
      during extreme ionospheric storms, GBAS users and GBAS ground facilities may
      experience different ionospheric delays, leading to considerable differential
      errors and threatening the safety of users. Therefore, ionospheric monitoring and
      assessment are important parts of GBAS integrity monitoring. To study the effects
      of the ionosphere on the GBAS of Guangdong Province, China, GPS data collected
      from 65 reference stations were processed using the improved "Simple Truth"
      algorithm. In addition, the ionospheric characteristics of Guangdong Province
      were calculated and an ionospheric threat model was established. Finally, we
      evaluated the influence of the standard deviation and maximum ionospheric
      gradient on GBAS. The results show that, under normal ionospheric conditions, the
      vertical protection level of GBAS was increased by 0.8 m for the largest over
      bound sigma v i g (sigma of vertical ionospheric gradient), and in the case of
      the maximum ionospheric gradient conditions, the differential correction error
      may reach 5 m. From an airworthiness perspective, when the satellite is at a low
      elevation, this interference does not cause airworthiness risks, but when the
      satellite is at a high elevation, this interference can cause airworthiness
      risks.

PMID- 29019952
TI  - Socioeconomic Differences and Trends in the Place of Death among Elderly People
      in China.
AB  - China is facing a dramatic aging of its population. Little is known about the
      factors that influence the place of death and the trends in the place of death
      for elderly people in China. The purposes of this study were: (1) to examine the
      impact of the socioeconomic status (SES) on place of death for elderly Chinese
      residents; and (2) to assess temporal trends in the place of death over the last
      15 years. Data were derived from the Chinese Longitudinal Healthy Longevity
      Survey (CLHLS) (1998-2012). Place-of-death as an outcome was dichotomized into
      either death at home or death outside the home. Logistic regression analyses were
      used to examine the impact of SES on place of death. The results showed that, of
      the 23,098 deaths during the study period, 87.78% occurred at home. The overall
      trend in home death has increased since 2005. SES was shown to be an important
      factor affecting place of death. The elderly with higher SES were more likely to
      die where health resources were concentrated, i.e., in a hospital or other type
      of institution. Our finding suggests that the trend towards a greater emphasis on
      death at home may call for the development of more supportive home care programs
      in China. Our finding also suggests that the socioeconomic differences in the
      place of death may be related to the availability of or access to health care
      services.

PMID- 29019955
TI  - Mechanical and Electrical Noise in Sense Channel of MEMS Vibratory Gyroscopes.
AB  - This paper presents a theoretical analysis of mechanical and electrical noise in
      the sense channel of micro-electromechanical systems (MEMS) vibratory gyroscopes.
      Closed-form expressions for the power spectral density (PSD) of the noise
      equivalent rate (NER) of gyroscopes in the open-loop and the force-rebalance
      operations are derived by using an averaged PSD model and an equivalent transfer
      function. The obtained expressions are verified through numerical simulations,
      demonstrating close agreements between the analytic and the numerical models.
      Based on the derived expressions for the PSD of the NER, the impacts of the modal
      frequency split, quality factor, and the gain of the feedback forcer, as well as
      the gain of the signal conditioning circuit, on the gyroscope noise
      characteristics are theoretically analyzed. In addition, the angle random walk
      (ARW) and the standard deviation of the NER are also discussed through the PSD
      models. Finally, the effects of the loop closing, the mode matching, and the gain
      of the feedback forcer on the PSD of the NER were verified via a MEMS vibratory
      gyroscope with a tunable modal frequency split.

PMID- 29019956
TI  - Anti-Diabetic Potential of Ocimum gratissimum Leaf Fractions in Fortified Diet
      Fed Streptozotocin Treated Rat Model of Type-2 Diabetes.
AB  - Background: Ocimum gratissimum (OG) is used in the traditional management of
      diabetes in Nigeria. This study investigated the anti-diabetic potential of OG
      leaf fractions (OGLF) in a rat model of Type-2 diabetes (T2D). Method: Methanol
      crude extract of OG leaf was fractionated with solvents of increasing order of
      polarity (n-hexane, chloroform, ethyl-acetate, n-butanol and water). The anti
      diabetic potential of the fractions was evaluated in vivo. T2D was induced in
      Albino Wistar rats and treated with OGLF. Result: The T2D rats showed significant
      elevation in serum levels of fasting blood glucose (FBG), liver and kidney
      function biomarkers. At 4-weeks of intervention with OGLF, the untreated diabetic
      control group maintained severe hyperglycaemia in the presence of 61.7% serum
      insulin, 17.3% pancreatic beta-cell function (HOMA-beta) and 51.5% Insulin
      sensitivity. The glucose tolerance ability was enhanced in the n-butanol-fraction
      (OGb) treated group. With 74.8% available serum insulin and 38.6% improvement in
      insulin sensitivity, the OGb treated group had a 63.5% reduction in FBG and it
      was found to be most effective as it ameliorates a majority of the changes caused
      in the studied parameters in diabetic rats. Conclusions: The data from this study
      suggest that OGb fraction is a potential candidate for the development of an
      effective drug for the management of T2D.

PMID- 29019954
TI  - Weight Loss in Advanced Chronic Kidney Disease: Should We Consider
      Individualised, Qualitative, ad Libitum Diets? A Narrative Review and Case Study.
AB  - In advanced chronic kidney disease, obesity may bring a survival advantage, but
      many transplant centres demand weight loss before wait-listing for kidney graft.
      The case here described regards a 71-year-old man, with obesity-related
      glomerulopathy; referral data were: weight 110 kg, Body Mass Index (BMI) 37
      kg/m2, serum creatinine (sCr) 5 mg/dL, estimated glomerular filtration rate
      (eGFR) 23 mL/min, blood urea nitrogen (BUN) 75 mg/dL, proteinuria 2.3 g/day. A
      moderately restricted, low-protein diet allowed reduction in BUN (45-55 mg/dL)
      and good metabolic and kidney function stability, with a weight increase of 6 kg.
      Therefore, he asked to be enrolled in a weight-loss program to be wait-listed
      (the two nearest transplant centres required a BMI below 30 or 35 kg/m2). Since
      previous low-calorie diets were not successful and he was against a surgical
      approach, we chose a qualitative, ad libitum coach-assisted diet, freely
      available in our unit. In the first phase, the diet is dissociated; he lost 16 kg
      in 2 months, without need for dialysis. In the second maintenance phase, in which
      foods are progressively combined, he lost 4 kg in 5 months, allowing wait
      listing. Dialysis started one year later, and was followed by weight gain of
      about 5 kg. He resumed the maintenance diet, and his current body weight, 35
      months after the start of the diet, is 94 kg, with a BMI of 31.7 kg/m2, without
      clinical or biochemical signs of malnutrition. This case suggests that our
      patients can benefit from the same options available to non-CKD (chronic kidney
      disease) individuals, provided that strict multidisciplinary surveillance is
      assured.

PMID- 29019957
TI  - Application of Multilayer Perceptron with Automatic Relevance Determination on
      Weed Mapping Using UAV Multispectral Imagery.
AB  - Remote sensing techniques are routinely used in plant species discrimination and
      of weed mapping. In the presented work, successful Silybum marianum detection and
      mapping using multilayer neural networks is demonstrated. A multispectral camera
      (green-red-near infrared) attached on a fixed wing unmanned aerial vehicle (UAV)
      was utilized for the acquisition of high-resolution images (0.1 m resolution).
      The Multilayer Perceptron with Automatic Relevance Determination (MLP-ARD) was
      used to identify the S. marianum among other vegetation, mostly Avena sterilis L.
      The three spectral bands of Red, Green, Near Infrared (NIR) and the texture layer
      resulting from local variance were used as input. The S. marianum identification
      rates using MLP-ARD reached an accuracy of 99.54%. Tauhe study had an one year
      duration, meaning that the results are specific, although the accuracy shows the
      interesting potential of S. marianum mapping with MLP-ARD on multispectral UAV
      imagery.

PMID- 29019958
TI  - Laser-Based Lighting: Experimental Analysis and Perspectives.
AB  - This paper presents an extensive analysis of the operating principles,
      theoretical background, advantages and limitations of laser-based lighting
      systems. In the first part of the paper we discuss the main advantages and issues
      of laser-based lighting, and present a comparison with conventional LED-lighting
      technology. In the second part of the paper, we present original experimental
      data on the stability and reliability of phosphor layers for laser lighting,
      based on high light-intensity and high-temperature degradation tests. In the
      third part of the paper (for the first time) we present a detailed comparison
      between three different solutions for laser lighting, based on (i) transmissive
      phosphor layers; (ii) a reflective/angled phosphor layer; and (iii) a parabolic
      reflector, by discussing the advantages and drawbacks of each approach. The
      results presented within this paper can be used as a guideline for the
      development of advanced lighting systems based on laser diodes.

PMID- 29019959
TI  - Recent Advances in Nanoparticle Concentration and Their Application in Viral
      Detection Using Integrated Sensors.
AB  - Early disease diagnostics require rapid, sensitive, and selective detection
      methods for target analytes. Specifically, early viral detection in a point-of
      care setting is critical in preventing epidemics and the spread of disease.
      However, conventional methods such as enzyme-linked immunosorbent assays or cell
      cultures are cumbersome and difficult for field use due to the requirements of
      extensive lab equipment and highly trained personnel, as well as limited
      sensitivity. Recent advances in nanoparticle concentration have given rise to
      many novel detection methodologies, which address the shortcomings in modern
      clinical assays. Here, we review the primary, well-characterized methods for
      nanoparticle concentration in the context of viral detection via diffusion,
      centrifugation and microfiltration, electric and magnetic fields, and nano
      microfluidics. Details of the concentration mechanisms and examples of related
      applications provide valuable information to design portable, integrated sensors.
      This study reviews a wide range of concentration techniques and compares their
      advantages and disadvantages with respect to viral particle detection. We
      conclude by highlighting selected concentration methods and devices for next
      generation biosensing systems.

PMID- 29019960
TI  - Molecular Insights into the Potential Insecticidal Interaction of beta
      Dihydroagarofuran Derivatives with the H Subunit of V-ATPase.
AB  - Celangulin V (CV), one of dihydroagarofuran sesquiterpene polyesters isolated
      from Chinese bittersweet (Celastrus angulatus Maxim), is famous natural botanical
      insecticide. Decades of research suggests that is displays excellent insecticidal
      activity against some insects, such as Mythimna separata Walker. Recently, it has
      been validated that the H subunit of V-ATPase is one of the target proteins of
      the insecticidal dihydroagarofuran sesquiterpene polyesters. As a continuation of
      the development of new pesticides from these natural products, a series of beta
      dihydroagarofuran derivatives have been designed and synthesized. The compound JW
      3, an insecticidal derivative of CV with a p-fluorobenzyl group, exhibits higher
      insecticidal activity than CV. In this study, the potential inhibitory effect
      aused by the interaction of JW-3 with the H subunit of V-ATPase c was verified by
      confirmatory experiments at the molecular level. Both spectroscopic techniques
      and isothermal titration calorimetry measurements showed the binding of JW-3 to
      the subunit H of V-ATPase was specific and spontaneous. In addition, the possible
      mechanism of action of the compound was discussed. Docking results indicated
      compound JW-3 could bind well in 'the interdomain cleft' of the V-ATPase subunit
      H by the hydrogen bonding and make conformation of the ligand-protein complex
      become more stable. All results are the further validations of the hypothesis,
      that the target protein of insecticidal dihydroagarofuran sesquiterpene
      polyesters and their beta-dihydroagarofuran derivatives is the subunit H of V
      ATPase. The results also provide new ideas for developing pesticides acting on V
      ATPase of insects.

PMID- 29019961
TI  - The Role of the Social Network in Access to Psychosocial Services for Migrant
      Elderly-A Qualitative Study.
AB  - Abstract:Background: Despite high prevalence of mental problems among elderly
      migrants in The Netherlands, the use of psychosocial care services by this group
      is low. Scientific evidence points at the crucial role of social support for
      mental health and the use of psychosocial services. We therefore explored the
      role of social networks in the access to psychosocial care among elderly migrants
      in The Netherlands. Methods: A qualitative study was conducted using semi
      structured group interviews and individual interviews. The eight group and eleven
      individual interviews (respectively n = 58 and n = 11) were conducted in The
      Netherlands with Turkish, Moroccan, Surinamese, and Dutch elderly. The data were
      analysed through coding and comparing fragments and recognizing patterns.
      Results: Support of the social network is important to navigate to psychosocial
      care and is most frequently provided by children. However, the social network of
      elderly migrants is generally not able to meet the needs of the elderly. This is
      mostly due to poor mental health literacy of the social network, taboo, and
      stigma around mental illness and the busy lives of the social network members.
      Conclusions: Strategies to address help-seeking barriers should consider mental
      health literacy in elderly migrants as well as their social networks, and
      counteract taboos and stigma of mental health problems.

PMID- 29019962
TI  - The Modular Optical Underwater Survey System.
AB  - The Pacific Islands Fisheries Science Center deploys the Modular Optical
      Underwater Survey System (MOUSS) to estimate the species-specific, size
      structured abundance of commercially-important fish species in Hawaii and the
      Pacific Islands. The MOUSS is an autonomous stereo-video camera system designed
      for the in situ visual sampling of fish assemblages. This system is rated to 500
      m and its low-light, stereo-video cameras enable identification, counting, and
      sizing of individuals at a range of 0.5-10 m. The modular nature of MOUSS allows
      for the efficient and cost-effective use of various imaging sensors, power
      systems, and deployment platforms. The MOUSS is in use for surveys in Hawaii, the
      Gulf of Mexico, and Southern California. In Hawaiian waters, the system can
      effectively identify individuals to a depth of 250 m using only ambient light. In
      this paper, we describe the MOUSS's application in fisheries research, including
      the design, calibration, analysis techniques, and deployment mechanism.

PMID- 29019963
TI  - Organ-on-Chip Technology: Current State and Future Developments.
AB  - In the early days of pharmacy, the development of new drugs was frequently
      achieved by restless chemists who worked solitarily, day by day for years [...].

PMID- 29019964
TI  - Building IoT Services for Aging in Place Using Standard-Based IoT Platforms and
      Heterogeneous IoT Products.
AB  - An aging population and human longevity is a global trend. Many developed
      countries are struggling with the yearly increasing healthcare cost that
      dominantly affects their economy. At the same time, people living with old adults
      suffering from a progressive brain disorder such as Alzheimer's disease are
      enduring even more stress and depression than those patients while caring for
      them. Accordingly, seniors' ability to live independently and comfortably in
      their current home for as long as possible has been crucial to reduce the
      societal cost for caregiving and thus give family members peace of mind, called
      'aging in place' (AIP). In this paper we present a way of building AIP services
      using standard-based IoT platforms and heterogeneous IoT products. An AIP service
      platform is designed and created by combining previous standard-based IoT
      platforms in a collaborative way. A service composition tool is also created that
      allows people to create AIP services in an efficient way. To show practical
      usability of our proposed system, we choose a service scenario for medication
      compliance and implement a prototype service which could give old adults
      medication reminder appropriately at the right time (i.e., when it is time to
      need to take pills) through light and speaker at home but also wrist band and
      smartphone even outside the home.

PMID- 29019967
TI  - Fatty liver disease: turning the tide.

PMID- 29019965
TI  - Molecular Cloning, Recombinant Expression and Antifungal Activity of BnCPI, a
      Cystatin in Ramie (Boehmeria nivea L.).
AB  - Phytocystatins play multiple roles in plant growth, development and resistance to
      pests and other environmental stresses. A ramie (Boehmeria nivea L.)
      phytocystatin gene, designated as BnCPI, was isolated from a ramie cDNA library
      and its full-length cDNA was obtained by rapid amplification of cDNA ends (RACE).
      The full-length cDNA sequence (691 bp) consisted of a 303 bp open reading frame
      (ORF) encoding a protein of 100 amino acids with deduced molecular mass of 11.06
      kDa and a theoretical isoelectric point (pI) of 6.0. The alignment of genome DNA
      (accession no. MF153097) and cDNA sequences of BnCPI showed that an intron (~104
      bp) exists in the coding region. The BnCPI protein contains most of the highly
      conserved blocks including Gly5-Gly6 at the N-terminal, the reactive site motif
      QxVxG (Q49V50V51S52G53), the L79-W80 block and the [LVI]-[AGT]-[RKE]-[FY]-[AS]
      [VI]-x-[EDQV]-[HYFQ]-N (L22G23R24 F25A26V27 D28D29H30 N31) block that is common
      among plant cystatins. BLAST analysis indicated that BnCPI is similar to
      cystatins from Glycine max (77%), Glycine soja (76%), Hevea brasiliensis (75%)
      and Ricinus communis (75%). The BnCPI was subcloned into expression vector pSmart
      I and then overexpressed in Escherichia coli BL21 (DE3) as a His-tagged
      recombinant protein. The purified reBnCPI has a molecular mass of 11.4 kDa
      determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE). Purified reBnCPI can efficiently inhibit the protease activity of papain
      and ficin toward BANA (Nalpha-benzoyl-L-arginine-2-naphthyamide), as well as the
      mycelium growth of some important plant pathogenic fungi. The data further
      contribute to our understanding of the molecular functions of BnCPI.

PMID- 29019966
TI  - Transthoracic Balloon Pulmonary Valvuloplasty for Treatment of Congenial
      Pulmonary Atresia Patients with Intact Ventricular Septum.
AB  - BACKGROUND To summarize our clinical experience in performing transthoracic
      balloon pulmonary valvuloplasty for the treatment of patients suffering from
      congenial pulmonary atresia with intact ventricular septum (PA/IVS). MATERIAL AND
      METHODS Between April 2009 and April 2016, 38 patients with PA/IVS underwent
      transthoracic balloon pulmonary valvuloplasty in our hospital. All of them were
      combined with patent ductus arteriosus, tricuspid insufficiency, and atrial
      septal defect or patent foramen ovale. The valvuloplasty was performed from the
      right ventricular outflow tract through a median sternotomy incision under TEE
      guidance for all cases. RESULTS Thirty-five patients were successfully
      discharged, and 3 patients died after the operation. The 35 surviving patients
      were followed up. Spo2 in the 35 patients was 88-96% after the operation. The
      transpulmonary valvular gradient pressure was less than or equal to 30 mmHg in 31
      patients and between 36 and 52 mmHg in the other 4 patients. After the surgery,
      tricuspid regurgitation was significantly reduced. We found only 4 patients with
      moderate regurgitation, 5 patients with mild to moderate regurgitation, and mild
      regurgitation in the remaining 26 patients. Five patients underwent a second
      stage operation, including biventricular repair in 4 patients and ligation of
      ductus arteriosus in 1 patient. CONCLUSIONS The application of transthoracic
      balloon pulmonary valvuloplasty for the treatment of PA/IVS is minimally invasive
      and safe, which has great significance for improving the curative effect for this
      condition and reducing operation mortality.

PMID- 29019968
TI  - Fighting the fatty liver.

PMID- 29019970
TI  - Emissions: We have the technology.

PMID- 29019972
TI  - Policy: Getting political.

PMID- 29019971
TI  - The real climate debate.

PMID- 29019969
TI  - Sea change.

PMID- 29019973
TI  - Climate change.

PMID- 29019974
TI  - The state of the art in stem cell biology and regenerative medicine: the end of
      the beginning.
AB  - With translational stem cell biology and Regenerative Medicine (the field to
      which the former gave rise) now over a quarter century old, it is time to take
      stock of where we have been and where we are going. This editorial overview,
      which serves as an introduction to this special issue of Pediatric Research
      dedicated to these fields, reinforces the notion that stem cells are ultimately
      intrinsic parts of developmental biology, for which Pediatrics represents the
      clinical face. Although stem cells provide the cellular basis for a great deal of
      only recently recognized plasticity programmed into the developing and
      postdevelopmental organism, and although there is enormous promise in harnessing
      this plasticity for therapeutic advantage, their successful use rests on a deep
      understanding of their developmental imperatives and the developmental programs
      in which they engage. The potential uses of stems are ranked and discussed in the
      order of most readily achievable to those requiring extensively more work.
      Although that order may not be what was contemplated at the field's birth, we
      nevertheless retain an optimism for the ultimate positive impact of exploiting
      this fundamental biology for the well-being of children.

PMID- 29019977
TI  - Neurobiology: Domains to the rescue for Rett syndrome.

PMID- 29019976
TI  - Nucleosome-Chd1 structure and implications for chromatin remodelling.
AB  - Chromatin-remodelling factors change nucleosome positioning and facilitate DNA
      transcription, replication, and repair. The conserved remodelling factor
      chromodomain-helicase-DNA binding protein 1(Chd1) can shift nucleosomes and
      induce regular nucleosome spacing. Chd1 is required for the passage of RNA
      polymerase IIthrough nucleosomes and for cellular pluripotency. Chd1 contains the
      DNA-binding domains SANT and SLIDE, a bilobal motor domain that hydrolyses ATP,
      and a regulatory double chromodomain. Here we report the cryo-electron microscopy
      structure of Chd1 from the yeast Saccharomyces cerevisiae bound to a nucleosome
      at a resolution of 4.8 A. Chd1 detaches two turns of DNA from the histone octamer
      and binds between the two DNA gyres in a state poised for catalysis. The SANT and
      SLIDE domains contact detached DNA around superhelical location (SHL) -7 of the
      first DNA gyre. The ATPase motor binds the second DNA gyre at SHL +2 and is
      anchored to the N-terminal tail of histone H4, as seen in a recent nucleosome
      Snf2 ATPase structure. Comparisons with published results reveal that the double
      chromodomain swings towards nucleosomal DNA at SHL +1, resulting in ATPase
      closure. The ATPase can then promote translocation of DNA towards the nucleosome
      dyad, thereby loosening the first DNA gyre and remodelling the nucleosome.
      Translocation may involve ratcheting of the two lobes of the ATPase, which is
      trapped in a pre- or post-translocation state in the absence or presence,
      respectively, of transition state-mimicking compounds.

PMID- 29019978
TI  - The prevalence of Plasmodium falciparum in sub-Saharan Africa since 1900.
AB  - Malaria transmission is influenced by climate, land use and deliberate
      interventions. Recent declines have been observed in malaria transmission. Here
      we show that the African continent has witnessed a long-term decline in the
      prevalence of Plasmodium falciparum from 40% prevalence in the period 1900-1929
      to 24% prevalence in the period 2010-2015, a trend that has been interrupted by
      periods of rapidly increasing or decreasing transmission. The cycles and trend
      over the past 115 years are inconsistent with explanations in terms of climate or
      deliberate intervention alone. Previous global initiatives have had minor impacts
      on malaria transmission, and a historically unprecedented decline has been
      observed since 2000. However, there has been little change in the high
      transmission belt that covers large parts of West and Central Africa. Previous
      efforts to model the changing patterns of P. falciparum transmission intensity in
      Africa have been limited to the past 15 years or have used maps drawn from
      historical expert opinions. We provide quantitative data, from 50,424 surveys at
      36,966 geocoded locations, that covers 115 years of malaria history in sub
      Saharan Africa; inferring from these data to future trends, we would expect
      continued reductions in malaria transmission, punctuated with resurgences.

PMID- 29019979
TI  - Cryo-electron microscopy structure of the lysosomal calcium-permeable channel
      TRPML3.
AB  - The modulation of ion channel activity by lipids is increasingly recognized as a
      fundamental component of cellular signalling. The transient receptor potential
      mucolipin (TRPML) channel family belongs to the TRP superfamily and is composed
      of three members: TRPML1-TRPML3. TRPMLs are the major Ca2+-permeable channels on
      late endosomes and lysosomes (LEL). They regulate the release of Ca2+ from
      organelles, which is important for various physiological processes, including
      organelle trafficking and fusion. Loss-of-function mutations in the MCOLN1 gene,
      which encodes TRPML1, cause the neurodegenerative lysosomal storage disorder
      mucolipidosis type IV, and a gain-of-function mutation (Ala419Pro) in TRPML3
      gives rise to the varitint-waddler (Va) mouse phenotype. Notably, TRPML channels
      are activated by the low-abundance and LEL-enriched signalling lipid
      phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2), whereas other
      phosphoinositides such as PtdIns(4,5)P2, which is enriched in plasma membranes,
      inhibit TRPMLs. Conserved basic residues at the N terminus of the channel are
      important for activation by PtdIns(3,5)P2 and inhibition by PtdIns(4,5)P2.
      However, owing to a lack of structural information, the mechanism by which TRPML
      channels recognize PtdIns(3,5)P2 and increase their Ca2+ conductance remains
      unclear. Here we present the cryo-electron microscopy (cryo-EM) structure of a
      full-length TRPML3 channel from the common marmoset (Callithrix jacchus) at an
      overall resolution of 2.9 A. Our structure reveals not only the molecular basis
      of ion conduction but also the unique architecture of TRPMLs, wherein the voltage
      sensor-like domain is linked to the pore via a cytosolic domain that we term the
      mucolipin domain. Combined with functional studies, these data suggest that the
      mucolipin domain is responsible for PtdIns(3,5)P2 binding and subsequent channel
      activation, and that it acts as a 'gating pulley' for lipid-dependent TRPML
      gating.

PMID- 29019975
TI  - Enhancing GTEx by bridging the gaps between genotype, gene expression, and
      disease.
AB  - Genetic variants have been associated with myriad molecular phenotypes that
      provide new insight into the range of mechanisms underlying genetic traits and
      diseases. Identifying any particular genetic variant's cascade of effects, from
      molecule to individual, requires assaying multiple layers of molecular
      complexity. We introduce the Enhancing GTEx (eGTEx) project that extends the GTEx
      project to combine gene expression with additional intermediate molecular
      measurements on the same tissues to provide a resource for studying how genetic
      differences cascade through molecular phenotypes to impact human health.

PMID- 29019980
TI  - Radically truncated MeCP2 rescues Rett syndrome-like neurological defects.
AB  - Heterozygous mutations in the X-linked MECP2 gene cause the neurological disorder
      Rett syndrome. The methyl-CpG-binding protein 2 (MeCP2) protein is an epigenetic
      reader whose binding to chromatin primarily depends on 5-methylcytosine.
      Functionally, MeCP2 has been implicated in several cellular processes on the
      basis of its reported interaction with more than 40 binding partners, including
      transcriptional co-repressors (for example, the NCoR/SMRT complex),
      transcriptional activators, RNA, chromatin remodellers, microRNA-processing
      proteins and splicing factors. Accordingly, MeCP2 has been cast as a multi
      functional hub that integrates diverse processes that are essential in mature
      neurons. At odds with the concept of broad functionality, missense mutations that
      cause Rett syndrome are concentrated in two discrete clusters coinciding with
      interaction sites for partner macromolecules: the methyl-CpG binding domain and
      the NCoR/SMRT interaction domain. Here we test the hypothesis that the single
      dominant function of MeCP2 is to physically connect DNA with the NCoR/SMRT
      complex, by removing almost all amino-acid sequences except the methyl-CpG
      binding and NCoR/SMRT interaction domains. We find that mice expressing truncated
      MeCP2 lacking both the N- and C-terminal regions (approximately half of the
      native protein) are phenotypically near-normal; and those expressing a minimal
      MeCP2 additionally lacking a central domain survive for over one year with only
      mild symptoms. This minimal protein is able to prevent or reverse neurological
      symptoms when introduced into MeCP2-deficient mice by genetic activation or virus
      mediated delivery to the brain. Thus, despite evolutionary conservation of the
      entire MeCP2 protein sequence, the DNA and co-repressor binding domains alone are
      sufficient to avoid Rett syndrome-like defects and may therefore have therapeutic
      utility.

PMID- 29019981
TI  - Structure of mammalian endolysosomal TRPML1 channel in nanodiscs.
AB  - Transient receptor potential mucolipin 1 (TRPML1) is a cation channel located
      within endosomal and lysosomal membranes. Ubiquitously expressed in mammalian
      cells, its loss-of-function mutations are the direct cause of type IV
      mucolipidosis, an autosomal recessive lysosomal storage disease. Here we present
      the single-particle electron cryo-microscopy structure of the mouse TRPML1
      channel embedded in nanodiscs. Combined with mutagenesis analysis, the TRPML1
      structure reveals that phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2)
      binds to the N terminus of the channel-distal from the pore-and the helix-turn
      helix extension between segments S2 and S3 probably couples ligand binding to
      pore opening. The tightly packed selectivity filter contains multiple ion-binding
      sites, and the conserved acidic residues form the luminal Ca2+-blocking site that
      confers luminal pH and Ca2+ modulation on channel conductance. A luminal linker
      domain forms a fenestrated canopy atop the channel, providing several luminal ion
      passages to the pore and creating a negative electrostatic trap, with a
      preference for divalent cations, at the luminal entrance. The structure also
      reveals two equally distributed S4-S5 linker conformations in the closed channel,
      suggesting an S4-S5 linker-mediated PtdInsP2 gating mechanism among TRPML
      channels.

PMID- 29019982
TI  - Structural phase transition in monolayer MoTe2 driven by electrostatic doping.
AB  - Monolayers of transition-metal dichalcogenides (TMDs) exhibit numerous crystal
      phases with distinct structures, symmetries and physical properties. Exploring
      the physics of transitions between these different structural phases in two
      dimensions may provide a means of switching material properties, with
      implications for potential applications. Structural phase transitions in TMDs
      have so far been induced by thermal or chemical means; purely electrostatic
      control over crystal phases through electrostatic doping was recently proposed as
      a theoretical possibility, but has not yet been realized. Here we report the
      experimental demonstration of an electrostatic-doping-driven phase transition
      between the hexagonal and monoclinic phases of monolayer molybdenum ditelluride
      (MoTe2). We find that the phase transition shows a hysteretic loop in Raman
      spectra, and can be reversed by increasing or decreasing the gate voltage. We
      also combine second-harmonic generation spectroscopy with polarization-resolved
      Raman spectroscopy to show that the induced monoclinic phase preserves the
      crystal orientation of the original hexagonal phase. Moreover, this structural
      phase transition occurs simultaneously across the whole sample. This
      electrostatic-doping control of structural phase transition opens up new
      possibilities for developing phase-change devices based on atomically thin
      membranes.

PMID- 29019983
TI  - Human TRPML1 channel structures in open and closed conformations.
AB  - Transient receptor potential mucolipin 1 (TRPML1) is a Ca2+-releasing cation
      channel that mediates the calcium signalling and homeostasis of lysosomes.
      Mutations in TRPML1 lead to mucolipidosis type IV, a severe lysosomal storage
      disorder. Here we report two electron cryo-microscopy structures of full-length
      human TRPML1: a 3.72-A apo structure at pH 7.0 in the closed state, and a 3.49-A
      agonist-bound structure at pH 6.0 in an open state. Several aromatic and
      hydrophobic residues in pore helix 1, helices S5 and S6, and helix S6 of a
      neighbouring subunit, form a hydrophobic cavity to house the agonist, suggesting
      a distinct agonist-binding site from that found in TRPV1, a TRP channel from a
      different subfamily. The opening of TRPML1 is associated with distinct dilations
      of its lower gate together with a slight structural movement of pore helix 1. Our
      work reveals the regulatory mechanism of TRPML channels, facilitates better
      understanding of TRP channel activation, and provides insights into the molecular
      basis of mucolipidosis type IV pathogenesis.

PMID- 29019986
TI  - Cancer development: Origins in the oesophagus.

PMID- 29019984
TI  - Transitional basal cells at the squamous-columnar junction generate Barrett's
      oesophagus.
AB  - In several organ systems, the transitional zone between different types of
      epithelium is a hotspot for pre-neoplastic metaplasia and malignancy, but the
      cells of origin for these metaplastic epithelia and subsequent malignancies
      remain unknown. In the case of Barrett's oesophagus, intestinal metaplasia occurs
      at the gastro-oesophageal junction, where stratified squamous epithelium
      transitions into simple columnar cells. On the basis of a number of experimental
      models, several alternative cell types have been proposed as the source of this
      metaplasia but in all cases the evidence is inconclusive: no model completely
      mimics Barrett's oesophagus in terms of the presence of intestinal goblet cells.
      Here we describe a transitional columnar epithelium with distinct basal
      progenitor cells (p63+KRT5+KRT7+) at the squamous-columnar junction of the upper
      gastrointestinal tract in a mouse model. We use multiple models and lineage
      tracing strategies to show that this squamous-columnar junction basal cell
      population serves as a source of progenitors for the transitional epithelium. On
      ectopic expression of CDX2, these transitional basal progenitors differentiate
      into intestinal-like epithelium (including goblet cells) and thereby reproduce
      Barrett's metaplasia. A similar transitional columnar epithelium is present at
      the transitional zones of other mouse tissues (including the anorectal junction)
      as well as in the gastro-oesophageal junction in the human gut. Acid reflux
      induced oesophagitis and the multilayered epithelium (believed to be a precursor
      of Barrett's oesophagus) are both characterized by the expansion of the
      transitional basal progenitor cells. Our findings reveal a previously
      unidentified transitional zone in the epithelium of the upper gastrointestinal
      tract and provide evidence that the p63+KRT5+KRT7+ basal cells in this zone are
      the cells of origin for multi-layered epithelium and Barrett's oesophagus.

PMID- 29019988
TI  - Mosaic mice ace functional genomics.

PMID- 29019989
TI  - A successful founder off the beaten path.

PMID- 29019990
TI  - Genetics of a hardy crop.

PMID- 29019991
TI  - Scientists need data visualization training.

PMID- 29019985
TI  - DNA sequencing at 40: past, present and future.
AB  - This review commemorates the 40th anniversary of DNA sequencing, a period in
      which we have already witnessed multiple technological revolutions and a growth
      in scale from a few kilobases to the first human genome, and now to millions of
      human and a myriad of other genomes. DNA sequencing has been extensively and
      creatively repurposed, including as a 'counter' for a vast range of molecular
      phenomena. We predict that in the long view of history, the impact of DNA
      sequencing will be on a par with that of the microscope.

PMID- 29019993
TI  - The key to unlocking CARs.

PMID- 29019992
TI  - The grand challenge of cellulosic biofuels.

PMID- 29019995
TI  - Epic $12 billion deal and FDA's approval raise CAR-T to new heights.

PMID- 29019987
TI  - Establishment of mouse expanded potential stem cells.
AB  - Mouse embryonic stem cells derived from the epiblast contribute to the somatic
      lineages and the germline but are excluded from the extra-embryonic tissues that
      are derived from the trophectoderm and the primitive endoderm upon reintroduction
      to the blastocyst. Here we report that cultures of expanded potential stem cells
      can be established from individual eight-cell blastomeres, and by direct
      conversion of mouse embryonic stem cells and induced pluripotent stem cells.
      Remarkably, a single expanded potential stem cell can contribute both to the
      embryo proper and to the trophectoderm lineages in a chimaera assay. Bona fide
      trophoblast stem cell lines and extra-embryonic endoderm stem cells can be
      directly derived from expanded potential stem cells in vitro. Molecular analyses
      of the epigenome and single-cell transcriptome reveal enrichment for blastomere
      specific signature and a dynamic DNA methylome in expanded potential stem cells.
      The generation of mouse expanded potential stem cells highlights the feasibility
      of establishing expanded potential stem cells for other mammalian species.

PMID- 29019996
TI  - Speed and oversight: FDA Commissioner Gottlieb acts on pledges.

PMID- 29019997
TI  - Recent patents related to the manufacture and repair of organs and organoids.

PMID- 29019999
TI  - The Supreme Court's interpretation of the biosimilars statute and the value of
      certainty.

PMID- 29020000
TI  - GM moths with autocidal gene tested outdoors in New York state.

PMID- 29020001
TI  - 23andMe wades further into drug discovery.

PMID- 29020003
TI  - Around the world in a month.

PMID- 29020002
TI  - First metabolic oncology inhibitor gets FDA green light, with record price tag.

PMID- 29020004
TI  - iML1515, a knowledgebase that computes Escherichia coli traits.

PMID- 29020006
TI  - Surge in insect resistance to transgenic crops and prospects for sustainability.
AB  - Transgenic crops have revolutionized insect pest control, but their effectiveness
      has been reduced by evolution of resistance in pests. We analyzed global
      monitoring data reported during the first two decades of transgenic crops, with
      each case representing the responses of one pest species in one country to one
      insecticidal protein from Bacillus thuringiensis (Bt). The cases of pest
      resistance to Bt crystalline (Cry) proteins produced by transgenic crops
      increased from 3 in 2005 to 16 in 2016. By contrast, in 17 other cases there was
      no decrease in pest susceptibility to Bt crops, including the recently introduced
      transgenic corn that produces a Bt vegetative insecticidal protein (Vip).
      Recessive inheritance of pest resistance has favored sustained susceptibility,
      but even when inheritance is not recessive, abundant refuges of non-Bt host
      plants have substantially delayed resistance. These insights may inform
      resistance management strategies to increase the durability of current and future
      transgenic crops.

PMID- 29020005
TI  - Antigen receptor repertoire profiling from RNA-seq data.

PMID- 29020007
TI  - Novartis trial validates inflammasome as chronic disease driver.

PMID- 29020008
TI  - Effect of statin on progression of symptomatic basilar artery stenosis and
      subsequent ischemic stroke.
AB  - BACKGROUND AND OBJECTIVE: Symptomatic basilar artery stenosis (BAS) is associated
      with high risk of ischemic stroke recurrence. We aimed to investigate whether
      statin therapy might prevent the progression of symptomatic BAS and stroke
      recurrence. METHODS: We retrospectively analyzed the data of patients with acute
      ischemia with symptomatic BAS, which was assessed using magnetic resonance
      angiogram (MRA) imaging on admission day, and 1 year later (or the day of the
      clinical event). The clinical endpoints were recurrent ischemic stroke and its
      composites, transient ischemic attack, coronary disease, and vascular death.
      RESULTS: Of the 153 patients with symptomatic BAS, 114 (74.5%) were treated with
      a statin after experiencing a stroke. Statin therapy significantly prevented the
      progression of symptomatic BAS (7.0% vs 28.2%) and induced regression (22.8% vs
      15.4%) compared to non-statin users (p = 0.002). There were 31 ischemic stroke
      incidences and 38 composite vascular events. Statin users showed significantly
      lower stroke recurrence (14.9% vs 35.9%, p = 0.05) and composite vascular events
      (17.5% vs 46.2%; odds ratio [OR], 0.29; 95% confidence interval [CI], 0.13-0.64)
      than those not using statins did. Recurrent stroke in the basilar territory and
      composite vascular events were more common in patients with progression of BAS
      than they were in other patients (OR, 5.16; 95% CI, 1.63-16.25 vs OR, 4.2; 95%
      CI, 1.56-11.34). CONCLUSION: Our study suggests that statin therapy may prevent
      the progression of symptomatic BAS and decrease the risk of subsequent ischemic
      stroke. Large randomized trials are needed to confirm this result.

PMID- 29020010
TI  - Assay optimisation and technology transfer for multi-site immuno-monitoring in
      vaccine trials.
AB  - Cellular immunological assays are important tools for the monitoring of responses
      to T-cell-inducing vaccine candidates. As these bioassays are often technically
      complex and require considerable experience, careful technology transfer between
      laboratories is critical if high quality, reproducible data that allows
      comparison between sites, is to be generated. The aim of this study, funded by
      the European Union Framework Program 7-funded TRANSVAC project, was to optimise
      Standard Operating Procedures and the technology transfer process to maximise the
      reproducibility of three bioassays for interferon-gamma responses: enzyme-linked
      immunosorbent assay (ELISA), ex-vivo enzyme-linked immunospot and intracellular
      cytokine staining. We found that the initial variability in results generated
      across three different laboratories reduced following a combination of Standard
      Operating Procedure harmonisation and the undertaking of side-by-side training
      sessions in which assay operators performed each assay in the presence of an
      assay 'lead' operator. Mean inter-site coefficients of variance reduced following
      this training session when compared with the pre-training values, most notably
      for the ELISA assay. There was a trend for increased inter-site variability at
      lower response magnitudes for the ELISA and intracellular cytokine staining
      assays. In conclusion, we recommend that on-site operator training is an
      essential component of the assay technology transfer process and combined with
      harmonised Standard Operating Procedures will improve the quality,
      reproducibility and comparability of data produced across different laboratories.
      These data may be helpful in ongoing discussions of the potential risk/benefit of
      centralised immunological assay strategies for large clinical trials versus
      decentralised units.

PMID- 29020009
TI  - Genome sequences of lower Great Lakes Microcystis sp. reveal strain-specific
      genes that are present and expressed in western Lake Erie blooms.
AB  - Blooms of the potentially toxic cyanobacterium Microcystis are increasing
      worldwide. In the Laurentian Great Lakes they pose major socioeconomic,
      ecological, and human health threats, particularly in western Lake Erie. However,
      the interpretation of "omics" data is constrained by the highly variable genome
      of Microcystis and the small number of reference genome sequences from strains
      isolated from the Great Lakes. To address this, we sequenced two Microcystis
      isolates from Lake Erie (Microcystis aeruginosa LE3 and M. wesenbergii LE013-01)
      and one from upstream Lake St. Clair (M. cf aeruginosa LSC13-02), and compared
      these data to the genomes of seventeen Microcystis spp. from across the globe as
      well as one metagenome and seven metatranscriptomes from a 2014 Lake Erie
      Microcystis bloom. For the publically available strains analyzed, the core genome
      is ~1900 genes, representing ~11% of total genes in the pan-genome and ~45% of
      each strain's genome. The flexible genome content was related to Microcystis
      subclades defined by phylogenetic analysis of both housekeeping genes and total
      core genes. To our knowledge this is the first evidence that the flexible genome
      is linked to the core genome of the Microcystis species complex. The majority of
      strain-specific genes were present and expressed in bloom communities in Lake
      Erie. Roughly 8% of these genes from the lower Great Lakes are involved in genome
      plasticity (rapid gain, loss, or rearrangement of genes) and resistance to
      foreign genetic elements (such as CRISPR-Cas systems). Intriguingly, strain
      specific genes from Microcystis cultured from around the world were also present
      and expressed in the Lake Erie blooms, suggesting that the Microcystis pangenome
      is truly global. The presence and expression of flexible genes, including strain
      specific genes, suggests that strain-level genomic diversity may be important in
      maintaining Microcystis abundance during bloom events.

PMID- 29020011
TI  - A microfluidic renal proximal tubule with active reabsorptive function.
AB  - In the kidney, the renal proximal tubule (PT) reabsorbs solutes into the
      peritubular capillaries through active transport. Here, we replicate this
      reabsorptive function in vitro by engineering a microfluidic PT. The microfluidic
      PT architecture comprises a porous membrane with user-defined submicron surface
      topography separating two microchannels representing a PT filtrate lumen and a
      peritubular capillary lumen. Human PT epithelial cells and microvascular
      endothelial cells in respective microchannels created a PT-like reabsorptive
      barrier. Co-culturing epithelial and endothelial cells in the microfluidic
      architecture enhanced viability, metabolic activity, and compactness of the
      epithelial layer. The resulting tissue expressed tight junctions, kidney-specific
      morphology, and polarized expression of kidney markers. The microfluidic PT
      actively performed sodium-coupled glucose transport, which could be modulated by
      administration of a sodium-transport inhibiting drug. The microfluidic PT
      reproduces human physiology at the cellular and tissue levels, and measurable
      tissue function which can quantify kidney pharmaceutical efficacy and toxicity.

PMID- 29020012
TI  - Wearable sensors objectively measure gait parameters in Parkinson's disease.
AB  - Distinct gait characteristics like short steps and shuffling gait are
      prototypical signs commonly observed in Parkinson's disease. Routinely assessed
      by observation through clinicians, gait is rated as part of categorical clinical
      scores. There is an increasing need to provide quantitative measurements of gait,
      e.g. to provide detailed information about disease progression. Recently, we
      developed a wearable sensor-based gait analysis system as diagnostic tool that
      objectively assesses gait parameter in Parkinson's disease without the need of
      having a specialized gait laboratory. This system consists of inertial sensor
      units attached laterally to both shoes. The computed target of measures are
      spatiotemporal gait parameters including stride length and time, stance phase
      time, heel-strike and toe-off angle, toe clearance, and inter-stride variation
      from gait sequences. To translate this prototype into medical care, we conducted
      a cross-sectional study including 190 Parkinson's disease patients and 101 age
      matched controls and measured gait characteristics during a 4x10 meter walk at
      the subjects' preferred speed. To determine intraindividual changes in gait, we
      monitored the gait characteristics of 63 patients longitudinally. Cross-sectional
      analysis revealed distinct spatiotemporal gait parameter differences reflecting
      typical Parkinson's disease gait characteristics including short steps, shuffling
      gait, and postural instability specific for different disease stages and levels
      of motor impairment. The longitudinal analysis revealed that gait parameters were
      sensitive to changes by mirroring the progressive nature of Parkinson's disease
      and corresponded to physician ratings. Taken together, we successfully show that
      wearable sensor-based gait analysis reaches clinical applicability providing a
      high biomechanical resolution for gait impairment in Parkinson's disease. These
      data demonstrate the feasibility and applicability of objective wearable sensor
      based gait measurement in Parkinson's disease reaching high technological
      readiness levels for both, large scale clinical studies and individual patient
      care.

PMID- 29020014
TI  - The structured 'low temperature' phase of the retinal population code.
AB  - Recent advances in experimental techniques have allowed the simultaneous
      recordings of populations of hundreds of neurons, fostering a debate about the
      nature of the collective structure of population neural activity. Much of this
      debate has focused on the empirical findings of a phase transition in the
      parameter space of maximum entropy models describing the measured neural
      probability distributions, interpreting this phase transition to indicate a
      critical tuning of the neural code. Here, we instead focus on the possibility
      that this is a first-order phase transition which provides evidence that the real
      neural population is in a 'structured', collective state. We show that this
      collective state is robust to changes in stimulus ensemble and adaptive state. We
      find that the pattern of pairwise correlations between neurons has a strength
      that is well within the strongly correlated regime and does not require fine
      tuning, suggesting that this state is generic for populations of 100+ neurons. We
      find a clear correspondence between the emergence of a phase transition, and the
      emergence of attractor-like structure in the inferred energy landscape. A
      collective state in the neural population, in which neural activity patterns
      naturally form clusters, provides a consistent interpretation for our results.

PMID- 29020016
TI  - Autonomous dynamic obstacle avoidance for bacteria-powered microrobots (BPMs)
      with modified vector field histogram.
AB  - In order to broaden the use of microrobots in practical fields, autonomous
      control algorithms such as obstacle avoidance must be further developed. However,
      most previous studies of microrobots used manual motion control to navigate past
      tight spaces and obstacles while very few studies demonstrated the use of
      autonomous motion. In this paper, we demonstrated a dynamic obstacle avoidance
      algorithm for bacteria-powered microrobots (BPMs) using electric field in fluidic
      environments. A BPM consists of an artificial body, which is made of SU-8, and a
      high dense layer of harnessed bacteria. BPMs can be controlled using externally
      applied electric fields due to the electrokinetic property of bacteria. For
      developing dynamic obstacle avoidance for BPMs, a kinematic model of BPMs was
      utilized to prevent collision and a finite element model was used to
      characteristic the deformation of an electric field near the obstacle walls. In
      order to avoid fast moving obstacles, we modified our previously static obstacle
      avoidance approach using a modified vector field histogram (VFH) method. To
      validate the advanced algorithm in experiments, magnetically controlled moving
      obstacles were used to intercept the BPMs as the BPMs move from the initial
      position to final position. The algorithm was able to successfully guide the BPMs
      to reach their respective goal positions while avoiding the dynamic obstacles.

PMID- 29020015
TI  - Anti-inflammatory and wound healing activities of calophyllolide isolated from
      Calophyllum inophyllum Linn.
AB  - Due to the high-cost and limitations of current wound healing treatments, the
      search for alternative approaches or drugs, particularly from medicinal plants,
      is of key importance. In this study, we report anti-inflammatory and wound
      healing activities of the major calophyllolide (CP) compound isolated from
      Calophyllum inophyllum Linn. The results showed that CP had no effect on HaCaT
      cell viability over a range of concentrations. CP reduced fibrosis formation and
      effectively promoted wound closure in mouse model without causing body weight
      loss. The underlying molecular mechanisms of wound repair by CP was investigated.
      CP markedly reduced MPO activity, and increased M2 macrophage skewing, as shown
      by up-regulation of M2-related gene expression, which is beneficial to the wound
      healing process. CP treatment prevented a prolonged inflammatory process by down
      regulation of the pro-inflammatory cytokines-IL-1beta, IL-6, TNF-alpha, but up
      regulation of the anti-inflammatory cytokine, IL-10. This study is the first to
      indicate a plausible role for CP in accelerating the process of wound healing
      through anti-inflammatory activity mechanisms, namely, by regulation of
      inflammatory cytokines, reduction in MPO, and switching of macrophages to an M2
      phenotype. These findings may enable the utilization of CP as a potent
      therapeutic for cutaneous wound healing.

PMID- 29020018
TI  - Probabilistic-numerical assessment of pyroclastic current hazard at Campi Flegrei
      and Naples city: Multi-VEI scenarios as a tool for "full-scale" risk management.
AB  - The Campi Flegrei volcanic field (Italy) poses very high risk to the highly
      urbanized Neapolitan area. Eruptive history was dominated by explosive activity
      producing pyroclastic currents (hereon PCs; acronym for Pyroclastic Currents)
      ranging in scale from localized base surges to regional flows. Here we apply
      probabilistic numerical simulation approaches to produce PC hazard maps, based on
      a comprehensive spectrum of flow properties and vent locations. These maps are
      incorporated in a Geographic Information System (GIS) and provide all probable
      Volcanic Explosivity Index (VEI) scenarios from different source vents in the
      caldera, relevant for risk management planning. For each VEI scenario, we report
      the conditional probability for PCs (i.e., the probability for a given area to be
      affected by the passage of PCs in case of a PC-forming explosive event) and
      related dynamic pressure. Model results indicate that PCs from VEI<4 events would
      be confined within the Campi Flegrei caldera, PC propagation being impeded by the
      northern and eastern caldera walls. Conversely, PCs from VEI 4-5 events could
      invade a wide area beyond the northern caldera rim, as well as part of the Naples
      metropolitan area to the east. A major controlling factor of PC dispersal is
      represented by the location of the vent area. PCs from the potentially largest
      eruption scenarios (analogous to the ~15 ka, VEI 6 Neapolitan Yellow Tuff or even
      the ~39 ka, VEI 7 Campanian Ignimbrite extreme event) would affect a large part
      of the Campanian Plain to the north and the city of Naples to the east. Thus, in
      case of renewal of eruptive activity at Campi Flegrei, up to 3 million people
      will be potentially exposed to volcanic hazard, pointing out the urgency of an
      emergency plan. Considering the present level of uncertainty in forecasting the
      future eruption type, size and location (essentially based on statistical
      analysis of previous activity), we suggest that appropriate planning measures
      should face at least the VEI 5 reference scenario (at least 2 occurrences
      documented in the last 10 ka).

PMID- 29020017
TI  - Normal mode-guided transition pathway generation in proteins.
AB  - The biological function of proteins is closely related to its structural motion.
      For instance, structurally misfolded proteins do not function properly. Although
      we are able to experimentally obtain structural information on proteins, it is
      still challenging to capture their dynamics, such as transition processes.
      Therefore, we need a simulation method to predict the transition pathways of a
      protein in order to understand and study large functional deformations. Here, we
      present a new simulation method called normal mode-guided elastic network
      interpolation (NGENI) that performs normal modes analysis iteratively to predict
      transition pathways of proteins. To be more specific, NGENI obtains displacement
      vectors that determine intermediate structures by interpolating the distance
      between two end-point conformations, similar to a morphing method called elastic
      network interpolation. However, the displacement vector is regarded as a linear
      combination of the normal mode vectors of each intermediate structure, in order
      to enhance the physical sense of the proposed pathways. As a result, we can
      generate more reasonable transition pathways geometrically and thermodynamically.
      By using not only all normal modes, but also in part using only the lowest normal
      modes, NGENI can still generate reasonable pathways for large deformations in
      proteins. This study shows that global protein transitions are dominated by
      collective motion, which means that a few lowest normal modes play an important
      role in this process. NGENI has considerable merit in terms of computational cost
      because it is possible to generate transition pathways by partial degrees of
      freedom, while conventional methods are not capable of this.

PMID- 29020013
TI  - In utero and lactational exposure to low-doses of the pyrethroid insecticide
      cypermethrin leads to neurodevelopmental defects in male mice-An ethological and
      transcriptomic study.
AB  - Accumulating evidence suggests that developmental exposure to environmental
      chemicals may modify the course of brain development, ultimately leading to
      neuropsychiatric / neurodegenerative disorders later in life. In the present
      study, we assessed the impact of one of the most frequently used pesticides in
      both residential and agricultural applications - the synthetic pyrethroid
      cypermethrin (CYP) - on developmental neurotoxicity (DNT). Female mice were
      perinatally exposed to low doses of CYP (5 and 20 mg/kg body weight) from
      gestation to postnatal day 15. Behavioral analyses were performed during the
      offspring's early life and during adulthood. Postnatal analyses revealed that
      perinatal exposure to CYP disturbed motor development without modifying sensory
      and communicative skills. We found that later in life, CYP-exposed offspring
      expressed maladaptive behaviors in response to highly challenging tasks and
      abnormal sociability. Transcriptomic analyses performed in the offspring's brain
      at the end of the exposure, highlighted mitochondrial dysfunction as a relevant
      pathomechanism underlying CYP-induced DNT. Interestingly, several genes involved
      in proteostasis maintenance were also shown to be dysregulated suggesting that
      alterations in biogenesis, folding, trafficking and degradation of proteins may
      significantly contribute to CYP-related DNT. From a regulatory perspective, this
      study highlights that behavioral and transcriptomic analyses are complementary
      tools providing useful direction for better DNT characterization, and as such,
      should be used together more systematically.

PMID- 29020019
TI  - They're heating up: Internet search query trends reveal significant public
      interest in heat-not-burn tobacco products.
AB  - Heat-not-burn tobacco products, battery powered devices that heat leaf tobacco to
      approximately 500 degrees Fahrenheit to produce an inhalable aerosol, are being
      introduced in markets around the world. Japan, where manufacturers have marketed
      several heat-not-burn brands since 2014, has been the focal national test market,
      with the intention of developing global marketing strategies. We used Google
      search query data to estimate, for the first time, the scale and growth potential
      of heat-not-burn tobacco products. Average monthly searches for heat-not-burn
      products rose 1,426% (95%CI: 746,3574) between their first (2015) and second
      (2016) complete years on the market and an additional 100% (95%CI: 60, 173)
      between the products second (2016) and third years on the market (Jan-Sep 2017).
      There are now between 5.9 and 7.5 million heat-not-burn related Google searches
      in Japan each month based on September 2017 estimates. Moreover, forecasts
      relying on the historical trends suggest heat-not-burn searches will increase an
      additional 32% (95%CI: -4 to 79) during 2018, compared to current estimates for
      2017 (Jan-Sep), with continued growth thereafter expected. Contrasting heat-not
      burn's rise in Japan to electronic cigarettes' rise in the United States we find
      searches for heat-not-burn eclipsed electronic cigarette searches during April
      2016. Moreover, the change in average monthly queries for heat-not-burn in Japan
      between 2015 and 2017 was 399 (95% CI: 184, 1490) times larger than the change in
      average monthly queries for electronic cigarettes in the Unites States over the
      same time period, increasing by 2,956% (95% CI: 1729, 7304) compared to only 7%
      (95% CI: 3,13). Our findings are a clarion call for tobacco control leaders to
      ready themselves as heat-not-burn tobacco products will likely garner substantial
      interest as they are introduced into new markets. Public health practitioners
      should expand heat-not-burn tobacco product surveillance, adjust existing tobacco
      control strategies to account for heat-not-burn tobacco products, and
      preemptively study the health risks/benefits, popular perceptions, and health
      messaging around heat-not-burn tobacco products.

PMID- 29020020
TI  - Distribution and habitat use of red panda in the Chitwan-Annapurna Landscape of
      Nepal.
AB  - In Nepal, the red panda (Ailurus fulgens) has been sparsely studied, although its
      range covers a wide area. The present study was carried out in the previously
      untapped Chitwan-Annapurna Landscape (CHAL) situated in central Nepal with an aim
      to explore current distributional status and identify key habitat use. Extensive
      field surveys conducted in 10 red panda range districts were used to estimate
      species distribution by presence-absence occupancy modeling and to predict
      distribution by presence-only modeling. The presence of red pandas was recorded
      in five districts: Rasuwa, Nuwakot, Myagdi, Baglung and Dhading. The predictive
      distribution model indicated that 1,904.44 km2 of potential red panda habitat is
      available in CHAL with the protected area covering nearly 41% of the total
      habitat. The habitat suitability analysis based on the probability of occurrence
      showed only 16.58% (A = 315.81 km2) of the total potential habitat is highly
      suitable. Red Panda occupancy was estimated to be around 0.0667, indicating
      nearly 7% (218 km2) of the total habitat is occupied with an average detection
      probability of 0.4482+/-0.377. Based on the habitat use analysis, altogether
      eight variables including elevation, slope, aspect, proximity to water sources,
      bamboo abundance, height, cover, and seasonal precipitation were observed to have
      significant roles in the distribution of red pandas. In addition, 25 tree species
      were documented from red panda sign plots out of 165 species recorded in the
      survey area. Most common was Betula utilis followed by Rhododendron spp. and
      Abies spectabilis. The extirpation of red pandas in previously reported areas
      indicates a need for immediate action for the long-term conservation of this
      species in CHAL.

PMID- 29020022
TI  - The geological record and phylogeny of spider wasps (Hymenoptera: Pompilidae): A
      revision of fossil species and their phylogenetic placement.
AB  - Accurate fossil identification has become increasingly relevant with the
      widespread use of phylogenetic divergence time estimation methods, which rely on
      fossil data to determine clade hard-minimum ages. Here we revise, diagnose and
      illustrate known spider wasp (Hymenoptera: Pompilidae) fossil species and place
      them within the latest Pompilidae phylogenetic hypothesis. Ceropalites infelix
      Cockerell, from the Florissant Fossil Beds (Priabonian), is no longer recognized
      as Pompilidae, but as Aulacidae. Agenioideus saxigenus (Cockerell) comb. nov.,
      Deuteragenia wettweri (Statz) comb. nov., Caputelus scudderi (Cockerell, 1906)
      comb. nov., Pepsinites avitula (Cockerell, 1941) comb. nov., Pepsinites contentus
      (Theobald, 1937) comb. nov., Pepsinites florissantensis (Cockerell, 1906) comb.
      nov., Pepsinites laminarum (Rohwer, 1909) comb. nov., Pepsinites scelerosus
      (Meunier, 1919) comb. nov., Pepsinites cockerellae (Rohwer, 1909) comb. nov.,
      Pompilinites coquandi (Theobald, 1937) comb. nov., Pompilinites depressus (Statz,
      1936) comb. nov., Pompilites incertus (Theobald, 1937) comb. nov., Pompilites
      induratus (Heer, 1849) comb. nov., Pompilites fasciatus (Theobald, 1937) comb.
      nov., and Pompilites senex comb. nov. are new combinations. Twenty-three fossil
      species of spider wasps are now recognized in 13 genera. Four new genera are
      proposed: Caputelus Waichert & Pitts gen. nov., Pompilites Rodriguez gen. nov.,
      Pompilinites Rodriguez & Waichert gen. nov., and Pepsinites Rodriguez & Waichert
      gen. nov., of which the three latter are collective-group names for fossils with
      taxonomic uncertainty. One species of fossil spider wasp is described:
      Deuteragenia catalunyia Rodriguez, Waichert & Pitts sp. nov., from the Bellver
      deposits in Catalonia, Spain. Five of the 23 known species can be used to
      determine hard-minimum age for calibrations of genera stem-groups (Agenioideus,
      Anoplius, Cryptocheilus, Deuteragenia, Priocnemis). The fossil belonging to the
      stem-group of the tribe Ageniellini (Chubutholites) is not recommended for
      calibration because of the high uncertainty in its age and taxonomy. The
      remaining taxa can be assigned to the lineage comprising Pompilinae + Pepsinae
      (12 species) or crown-group Pompilidae (four species).

PMID- 29020021
TI  - Physiological, morphological, and ecological tradeoffs influence vertical habitat
      use of deep-diving toothed-whales in the Bahamas.
AB  - Dive capacity among toothed whales (suborder: Odontoceti) has been shown to
      generally increase with body mass in a relationship closely linked to the
      allometric scaling of metabolic rates. However, two odontocete species tagged in
      this study, the Blainville's beaked whale Mesoplodon densirostris and the
      Cuvier's beaked whale Ziphius cavirostris, confounded expectations of a simple
      allometric relationship, with exceptionally long (mean: 46.1 min & 65.4 min) and
      deep dives (mean: 1129 m & 1179 m), and comparatively small body masses (med.:
      842.9 kg & 1556.7 kg). These two species also exhibited exceptionally long
      recovery periods between successive deep dives, or inter-deep-dive intervals (M.
      densirostris: med. 62 min; Z. cavirostris: med. 68 min). We examined competing
      hypotheses to explain observed patterns of vertical habitat use based on body
      mass, oxygen binding protein concentrations, and inter-deep-dive intervals in an
      assemblage of five sympatric toothed whales species in the Bahamas. Hypotheses
      were evaluated using dive data from satellite tags attached to the two beaked
      whales (M. densirostris, n = 12; Z. cavirostris, n = 7), as well as melon-headed
      whales Peponocephala electra (n = 13), short-finned pilot whales Globicephala
      macrorhynchus (n = 15), and sperm whales Physeter macrocephalus (n = 27). Body
      mass and myoglobin concentration together explained only 36% of the variance in
      maximum dive durations. The inclusion of inter-deep-dive intervals, substantially
      improved model fits (R2 = 0.92). This finding supported a hypothesis that beaked
      whales extend foraging dives by exceeding aerobic dive limits, with the extension
      of inter-deep-dive intervals corresponding to metabolism of accumulated lactic
      acid. This inference points to intriguing tradeoffs between body size, access to
      prey in different depth strata, and time allocation within dive cycles. These
      tradeoffs and resulting differences in habitat use have important implications
      for spatial distribution patterns, and relative vulnerabilities to anthropogenic
      impacts.

PMID- 29020023
TI  - The continuous reaction time test for minimal hepatic encephalopathy validated by
      a randomized controlled multi-modal intervention-A pilot study.
AB  - BACKGROUND: Minimal hepatic encephalopathy (MHE) is clinically undetectable and
      the diagnosis requires psychometric tests. However, a lack of clarity exists as
      to whether the tests are in fact able to detect changes in cognition. AIM: To
      examine if the continuous reaction time test (CRT) can detect changes in
      cognition with anti-HE intervention in patients with cirrhosis and without
      clinically manifest hepatic encephalopathy (HE). METHODS: Firstly, we conducted a
      reproducibility analysis and secondly measured change in CRT induced by anti-HE
      treatment in a randomized controlled pilot study: We stratified 44 patients with
      liver cirrhosis and without clinically manifest HE according to a normal (n = 22)
      or abnormal (n = 22) CRT. Each stratum was then block randomized to receive
      multimodal anti-HE intervention (lactulose+branched-chain amino acids+rifaximin)
      or triple placebos for 3 months in a double-blinded fashion. The CRT is a simple
      PC-based test and the test result, the CRT index (normal threshold > 1.9),
      describes the patient's stability of alertness during the 10-minute test. Our
      study outcome was the change in CRT index in each group at study exit. The
      portosystemic encephalopathy (PSE) test, a paper-and-pencil test battery (normal
      threshold above -5), was used as a comparator test according to international
      guidelines. RESULTS: The patients with an abnormal CRT index who were randomized
      to receive the active intervention normalized or improved their CRT index (mean
      change 0.92 +/- 0.29, p = 0.01). Additionally, their PSE improved (change 3.85 +/
      1.83, p = 0.03). There was no such effect in any of the other study groups.
      CONCLUSION: In this cohort of patients with liver cirrhosis and no manifest HE,
      the CRT identified a group in whom cognition improved with intensive anti-HE
      intervention. This finding infers that the CRT can detect a response to treatment
      and might help in selecting patients for treatment.

PMID- 29020024
TI  - An application of the Continuous Opinions and Discrete Actions (CODA) model to
      adolescent smoking initiation.
AB  - We investigated the impact of peers' opinions on the smoking initiation process
      among adolescents. We applied the Continuous Opinions and Discrete Actions (CODA)
      model to study how social interactions change adolescents' opinions and behaviors
      about smoking. Through agent-based modeling (ABM), we simulated a population of
      2500 adolescents and compared smoking prevalence to data from 9 cohorts of
      adolescents in the National Survey on Drug Use and Health (NSDUH) from year 2001
      till 2014. Our model adjusts well for NSDUH data according to pseudo R2 values,
      which are at least 96%. Optimal parameter values indicate that adolescents
      exhibit imitator characteristics with regard to smoking opinions. The imitator
      characteristics suggests that teenagers tend to update their opinions
      consistently according to what others do, and these opinions later translate into
      smoking behaviors. As a result, peer influence from social networks plays a big
      role in the smoking initiation process and should be an important driver in
      policy formulation.

PMID- 29020026
TI  - Features of the normal choriocapillaris with OCT-angiography: Density estimation
      and textural properties.
AB  - The main objective of our work is to perform an in depth analysis of the
      structural features of normal choriocapillaris imaged with OCT Angiography.
      Specifically, we provide an optimal radius for a circular Region of Interest
      (ROI) to obtain a stable estimate of the subfoveal choriocapillaris density and
      characterize its textural properties using Markov Random Fields. On each
      binarized image of the choriocapillaris OCT Angiography we performed simulated
      measurements of the subfoveal choriocapillaris densities with circular Regions of
      Interest (ROIs) of different radii and with small random displacements from the
      center of the Foveal Avascular Zone (FAZ). We then calculated the variability of
      the density measure with different ROI radii. We then characterized the textural
      features of choriocapillaris binary images by estimating the parameters of an
      Ising model. For each image we calculated the Optimal Radius (OR) as the minimum
      ROI radius required to obtain a standard deviation in the simulation below 0.01.
      The density measured with the individual OR was 0.52 +/- 0.07 (mean +/- STD).
      Similar density values (0.51 +/- 0.07) were obtained using a fixed ROI radius of
      450 MUm. The Ising model yielded two parameter estimates (beta = 0.34 +/- 0.03;
      gamma = 0.003 +/- 0.012; mean +/- STD), characterizing pixel clustering and white
      pixel density respectively. Using the estimated parameters to synthetize new
      random textures via simulation we obtained a good reproduction of the original
      choriocapillaris structural features and density. In conclusion, we developed an
      extensive characterization of the normal subfoveal choriocapillaris that might be
      used for flow analysis and applied to the investigation pathological alterations.

PMID- 29020025
TI  - Worry about racial discrimination: A missing piece of the puzzle of Black-White
      disparities in preterm birth?
AB  - OBJECTIVES: The causes of the large and persistent Black-White disparity in
      preterm birth (PTB) are unknown. It is biologically plausible that chronic stress
      across a woman's life course could be a contributor. Prior research suggests that
      chronic worry about experiencing racial discrimination could affect PTB through
      neuroendocrine, vascular, or immune mechanisms involved in both responses to
      stress and the initiation of labor. This study aimed to examine the role of
      chronic worry about racial discrimination in Black-White disparities in PTB.
      METHODS: The data source was cross-sectional California statewide-representative
      surveys of 2,201 Black and 8,122 White, non-Latino, U.S.-born postpartum women
      with singleton live births during 2011-2014. Chronic worry about racial
      discrimination (chronic worry) was defined as responses of "very often" or
      "somewhat often" (vs. "not very often" or "never") to the question: "Overall
      during your life until now, how often have you worried that you might be treated
      or viewed unfairly because of your race or ethnic group?" Prevalence ratios (PRs)
      with 95% Confidence Intervals (CI) were calculated from sequential logistic
      regression models, before and after adjustment for multiple social/demographic,
      behavioral, and medical factors, to estimate the magnitude of: (a) PTB risks
      associated with chronic worry among Black women and among White women; and (b)
      Black-White disparities in PTB, before and after adjustment for chronic worry.
      RESULTS: Among Black and White women respectively, 36.9 (95% CI 32.9-40.9) % and
      5.5 (95% CI 4.5-6.5) % reported chronic worry about racial discrimination; rates
      were highest among Black women of higher income and education levels. Chronic
      worry was significantly associated with PTB among Black women before (PR 1.73,
      95% CI 1.12-2.67) and after (PR 2.00, 95% CI 1.33-3.01) adjustment for
      covariates. The unadjusted Black-White disparity in PTB (PR 1.59, 95%CI 1.21
      2.09) appeared attenuated and became non-significant after adjustment for chronic
      worry (PR 1.30, 95% CI 0.93-1.81); it appeared further attenuated after adding
      the covariates (PR 1.17, 95% CI 0.85-1.63). CONCLUSIONS: Chronic worry about
      racial discrimination may play an important role in Black-White disparities in
      PTB and may help explain the puzzling and repeatedly observed greater PTB
      disparities among more socioeconomically-advantaged women. Although the single
      measure of experiences of racial discrimination used in this study precluded
      examination of the role of other experiences of racial discrimination, such as
      overt incidents, it is likely that our findings reflect an association between
      one or more experiences of racial discrimination and PTB. Further research should
      examine a range of experiences of racial discrimination, including not only
      chronic worry but other psychological and emotional states and both subtle and
      overt incidents as well. These dramatic results from a large statewide
      representative study add to a growing-but not widely known-literature linking
      racism-related stress with physical health in general, and shed light on the
      links between racism-related stress and PTB specifically. Without being causally
      definitive, this study's findings should stimulate further research and heighten
      awareness of the potential role of unmeasured social variables, such as diverse
      experiences of racial discrimination, in racial disparities in health.

PMID- 29020027
TI  - An investigation of left/right driving rules on deviations while walking.
AB  - When traversing through an aperture, such as a doorway, people characteristically
      deviate towards the right. This rightward deviation can be explained by a
      rightward attentional bias which leads to rightward bisections in far space. It
      is also possible, however, that left or right driving practices affect the
      deviation. To explore this possibility, Australian (left-side drivers) and Swiss
      (right-side drivers) participants (n = 36 & 34) walked through the middle of an
      aperture. To control for the sway of the body, participants started with either
      their left or right foot. Sway had a significant effect on participants' position
      in the doorway and the amount of sway was greater for Australians-perhaps due to
      national differences in gait. There was a significant rightward deviation for the
      Swiss, but not for the Australians. It is suggested that driving practices have a
      small additive effect on rightward attentional biases whereby the bias is
      increased for people who drive on the right and reduced in people who drive on
      the left.

PMID- 29020028
TI  - Learning speed is affected by personality and reproductive investment in a
      songbird.
AB  - Individuals from different taxa, including songbirds, differ consistently in
      behaviour and personality when facing different situations. Although our
      understanding of animal behaviour has increased, knowledge about between
      individual differences in cognitive abilities is still limited. By using an
      experimental approach and a free-living songbird (Parus major) as a model, we
      attempted to understand between-individual differences in habituation to
      playbacks (as a proxy of learning speed), by investigating the role of
      personality, age and reproductive investment (clutch size). Pre-breeding males
      were tested for exploration (a proxy of personality) in standardized conditions.
      In addition, the same individuals were exposed to three playbacks in the field
      during incubation. Birds significantly moved less, stayed further away and
      overlapped less the playback with successive playback stimulation. While a
      decrease in the locomotor behaviour can be explained by personality, differences
      in habituation of overlapping were predicted by both reproductive investment and
      personality. Fast explorers habituated less. Moreover, males paired to females
      with larger clutches did not vary the intensity of overlapping. Since habituation
      requires information for recognition of non-threatening signals, personality may
      bias information gathering. While fast explorers may collect less information
      from the environment, slow explorers (reactive birds) seem to pay attention to
      environmental clues and collect detailed information. We provided evidence that
      the rate of habituation of behavioural responses, a proxy of cognitive abilities,
      may be affected by different factors and in a complex way.

PMID- 29020029
TI  - Something from nothing: Estimating consumption rates using propensity scores,
      with application to emissions reduction policies.
AB  - Consumption surveys often record zero purchases of a good because of a short
      observation window. Measures of distribution are then precluded and only mean
      consumption rates can be inferred. We show that Propensity Score Matching can be
      applied to recover the distribution of consumption rates. We demonstrate the
      method using the UK National Travel Survey, in which c.40% of motorist households
      purchase no fuel. Estimated consumption rates are plausible judging by
      households' annual mileages, and highly skewed. We apply the same approach to
      estimate CO2 emissions and outcomes of a carbon cap or tax. Reliance on means
      apparently distorts analysis of such policies because of skewness of the
      underlying distributions. The regressiveness of a simple tax or cap is
      overstated, and redistributive features of a revenue-neutral policy are
      understated.

PMID- 29020030
TI  - The first hyaenodont from the late Oligocene Nsungwe Formation of Tanzania:
      Paleoecological insights into the Paleogene-Neogene carnivore transition.
AB  - Throughout the Paleogene, most terrestrial carnivore niches in Afro-Arabia were
      occupied by Hyaenodonta, an extinct lineage of placental mammals. By the end of
      the Miocene, terrestrial carnivore niches had shifted to members of Carnivora, a
      clade with Eurasian origins. The transition from a hyaenodont-carnivore fauna to
      a carnivoran-carnivore fauna coincides with other ecological changes in Afro
      Arabia as tectonic conditions in the African Rift System altered climatic
      conditions and facilitated faunal exchange with Eurasia. Fossil bearing deposits
      in the Nsungwe Formation in southwestern Tanzania are precisely dated to ~25.2 Ma
      (late Oligocene), preserving a late Paleogene Afro-Arabian fauna on the brink of
      environmental transition, including the earliest fossil evidence of the split
      between Old World monkeys and apes. Here we describe a new hyaenodont from the
      Nsungwe Formation, Pakakali rukwaensis gen. et sp. nov., a bobcat-sized taxon
      known from a portion of the maxilla that preserves a deciduous third premolar and
      alveoli of dP4 and M1. The crown of dP3 bears an elongate parastyle and metastyle
      and a small, blade-like metacone. Based on alveolar morphology, the two more
      distal teeth successively increased in size and had relatively large protocones.
      Using a hyaenodont character-taxon matrix that includes deciduous dental
      characters, Bayesian phylogenetic methods resolve Pakakali within the clade
      Hyainailouroidea. A Bayesian biogeographic analysis of phylogenetic results
      resolve the Pakakali clade as Afro-Arabian in origin, demonstrating that this
      small carnivorous mammal was part of an endemic Afro-Arabian lineage that
      persisted into the Miocene. Notably, Pakakali is in the size range of carnivoran
      forms that arrived and began to diversify in the region by the early Miocene. The
      description of Pakakali is important for exploring hyaenodont ontogeny and
      potential influences of Afro-Arabian tectonic events upon mammalian evolution,
      providing a deep time perspective on the stability of terrestrial carnivore
      niches through time.

PMID- 29020032
TI  - Linking functional response and bioenergetics to estimate juvenile salmon growth
      in a reservoir food web.
AB  - Juvenile salmon (Oncorhynchus spp.) use of reservoir food webs is understudied.
      We examined the feeding behavior of subyearling Chinook salmon (O. tshawytscha)
      and its relation to growth by estimating the functional response of juvenile
      salmon to changes in the density of Daphnia, an important component of reservoir
      food webs. We then estimated salmon growth across a broad range of water
      temperatures and daily rations of two primary prey, Daphnia and juvenile American
      shad (Alosa sapidissima) using a bioenergetics model. Laboratory feeding
      experiments yielded a Type-II functional response curve: C = 29.858 P *(4.271 +
      P)-1 indicating that salmon consumption (C) of Daphnia was not affected until
      Daphnia densities (P) were < 30 . L-1. Past field studies documented Daphnia
      densities in lower Columbia River reservoirs of < 3 . L-1 in July but as high as
      40 . L-1 in August. Bioenergetics modeling indicated that subyearlings could not
      achieve positive growth above 22 degrees C regardless of prey type or consumption
      rate. When feeding on Daphnia, subyearlings could not achieve positive growth
      above 20 degrees C (water temperatures they commonly encounter in the lower
      Columbia River during summer). At 16-18 degrees C, subyearlings had to consume
      about 27,000 Daphnia . day-1 to achieve positive growth. However, when feeding on
      juvenile American shad, subyearlings had to consume 20 shad . day-1 at 16-18
      degrees C, or at least 25 shad . day-1 at 20 degrees C to achieve positive
      growth. Using empirical consumption rates and water temperatures from summer
      2013, subyearlings exhibited negative growth during July (-0.23 to -0.29 g . d-1)
      and August (-0.05 to -0.07 g . d-1). By switching prey from Daphnia to juvenile
      shad which have a higher energy density, subyearlings can partially compensate
      for the effects of higher water temperatures they experience in the lower
      Columbia River during summer. However, achieving positive growth as piscivores
      requires subyearlings to feed at higher consumption rates than they exhibited
      empirically. While our results indicate compromised growth in reservoir habitats,
      the long-term repercussions to salmon populations in the Columbia River Basin are
      unknown.

PMID- 29020031
TI  - Sudden cardiac death and pump failure death prediction in chronic heart failure
      by combining ECG and clinical markers in an integrated risk model.
AB  - BACKGROUND: Sudden cardiac death (SCD) and pump failure death (PFD) are common
      endpoints in chronic heart failure (CHF) patients, but prevention strategies are
      different. Currently used tools to specifically predict these endpoints are
      limited. We developed risk models to specifically assess SCD and PFD risk in CHF
      by combining ECG markers and clinical variables. METHODS: The relation of
      clinical and ECG markers with SCD and PFD risk was assessed in 597 patients
      enrolled in the MUSIC (MUerte Subita en Insuficiencia Cardiaca) study. ECG
      indices included: turbulence slope (TS), reflecting autonomic dysfunction; T-wave
      alternans (TWA), reflecting ventricular repolarization instability; and T-peak-to
      end restitution (DeltaalphaTpe) and T-wave morphology restitution (TMR), both
      reflecting changes in dispersion of repolarization due to heart rate changes.
      Standard clinical indices were also included. RESULTS: The indices with the
      greatest SCD prognostic impact were gender, New York Heart Association (NYHA)
      class, left ventricular ejection fraction, TWA, DeltaalphaTpe and TMR. For PFD,
      the indices were diabetes, NYHA class, DeltaalphaTpe and TS. Using a model with
      only clinical variables, the hazard ratios (HRs) for SCD and PFD for patients in
      the high-risk group (fifth quintile of risk score) with respect to patients in
      the low-risk group (first and second quintiles of risk score) were both greater
      than 4. HRs for SCD and PFD increased to 9 and 11 when using a model including
      only ECG markers, and to 14 and 13, when combining clinical and ECG markers.
      CONCLUSION: The inclusion of ECG markers capturing complementary pro-arrhythmic
      and pump failure mechanisms into risk models based only on standard clinical
      variables substantially improves prediction of SCD and PFD in CHF patients.

PMID- 29020033
TI  - Genotype combination contributes to psoriasis: An exhaustive algorithm
      perspective.
AB  - Researchers have learned that nearly all conditions and diseases have a genetic
      component. With the benefit of technological advances, many single-nucleotide
      polymorphisms (SNPs) have been found to be associated with the risk of complex
      disorders by using genome wide association studies (GWASs). Disease-associated
      SNPs are sometimes shared by healthy controls and cannot clearly distinguish
      affected individuals from unaffected ones. The combined effects of multiple
      independent SNPs contribute to the disease process, but revealing the
      relationship between genotype and phenotype based on the combinations remains a
      great challenge. In this study, by considering the disease prevalence rate, we
      conducted an exhaustive process to identify whether a genotype combination
      pattern would have a decisive effect on complex disorders. Based on genotype data
      for 68 reported SNPs in 8,372 psoriasis patients and 8,510 healthy controls, we
      found that putative causal genotype combination patterns (CGCPs) were only
      present in psoriasis patients, not in healthy subjects. These results suggested
      that psoriasis might be contributed by combined genotypes, complementing the
      traditional modest susceptibility of a single variant in a single gene for a
      complex disease. This work is the first systematic study to analyze genotype
      combinations based on the reported susceptibility genes, considering each
      individual among the cases and controls from the Chinese population, and could
      potentially advance disease-gene mapping and precision medicine due to the
      causality relationship between the candidate CGCPs and complex diseases.

PMID- 29020034
TI  - Tolerance analysis of chloroplast OsCu/Zn-SOD overexpressing rice under NaCl and
      NaHCO3 stress.
AB  - The 636-bp-long cDNA sequence of OsCu/Zn-SOD (AK059841) was cloned from Oryza
      sativa var. Longjing11 via reverse transcription polymerase chain reaction (RT
      PCR). The encoded protein comprised of 211 amino acids is highly homologous to
      Cu/Zn-SOD proteins from tuscacera rice and millet. Quantitative RT-PCR revealed
      that in rice, the level of OsCu/Zn-SOD gene expression was lowest in roots and
      was highest in petals and during the S5 leaf stage. Moreover, the expression
      level of OsCu/Zn-SOD gene expression decreased during the L5 leaf stage to
      maturity. The level of OsCu/Zn-SOD gene expression, however, was increased under
      saline-sodic stress and NaHCO3 stress. Germination tests under 125, 150, and 175
      mM NaCl revealed that OsCu/Zn-SOD-overexpressing lines performed better than the
      non-transgenic (NT) Longjing11 lines in terms of germination rate and height.
      Subjecting seedlings to NaHCO3 and water stress revealed that OsCu/Zn-SOD
      overexpressing lines performed better than NT in terms of SOD activity, fresh
      weight, root length, and height. Under simulated NaHCO3 stress, OsCu/Zn-SOD
      overexpressing lines performed better than NT in terms of survival rate (25.19% >
      6.67%) and yield traits (average grain weight 20.6 > 18.15 g). This study showed
      that OsCu/Zn-SOD gene overexpression increases the detoxification capacity of
      reactive oxygen species in O. sativa and reduces salt-induced oxidative damage.
      We also revealed the regulatory mechanism of OsCu/Zn-SOD enzyme in saline-sodic
      stress resistance in O. sativa. Moreover, we provided an experimental foundation
      for studying the mechanism of OsCu/Zn-SOD enzymes in the chloroplast.

PMID- 29020035
TI  - Correction: Decoupling of the PI3K Pathway via Mutation Necessitates
      Combinatorial Treatment in HER2+ Breast Cancer.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0133219.].

PMID- 29020038
TI  - Correction: Integrating Genetic, Neuropsychological and Neuroimaging Data to
      Model Early-Onset Obsessive Compulsive Disorder Severity.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0153846.].

PMID- 29020036
TI  - Mixtures of tense and relaxed state polymerized human hemoglobin regulate oxygen
      affinity and tissue construct oxygenation.
AB  - Pure tense (T) and relaxed (R) quaternary state polymerized human hemoglobins
      (PolyhHbs) were synthesized and their biophysical properties characterized, along
      with mixtures of T- and R-state PolyhHbs. It was observed that the oxygen
      affinity of PolyhHb mixtures varied linearly with T-state mole fraction.
      Computational analysis of PolyhHb facilitated oxygenation of a single fiber in a
      hepatic hollow fiber (HF) bioreactor was performed to evaluate the oxygenation
      potential of T- and R-state PolyhHb mixtures. PolyhHb mixtures with T-state mole
      fractions greater than 50% resulted in hypoxic and hyperoxic zones occupying less
      than 5% of the total extra capillary space (ECS). Under these conditions, the
      ratio of the pericentral volume to the perivenous volume in the ECS doubled as
      the T-state mole fraction increased from 50 to 100%. These results show the
      effect of varying the T/R-state PolyhHb mole fraction on oxygenation of tissue
      engineered constructs and their potential to oxygenate tissues.

PMID- 29020037
TI  - A conserved fungal glycosyltransferase facilitates pathogenesis of plants by
      enabling hyphal growth on solid surfaces.
AB  - Pathogenic fungi must extend filamentous hyphae across solid surfaces to cause
      diseases of plants. However, the full inventory of genes which support this is
      incomplete and many may be currently concealed due to their essentiality for the
      hyphal growth form. During a random T-DNA mutagenesis screen performed on the
      pleomorphic wheat (Triticum aestivum) pathogen Zymoseptoria tritici, we acquired
      a mutant unable to extend hyphae specifically when on solid surfaces. In contrast
      "yeast-like" growth, and all other growth forms, were unaffected. The inability
      to extend surface hyphae resulted in a complete loss of virulence on plants. The
      affected gene encoded a predicted type 2 glycosyltransferase (ZtGT2). Analysis of
      >800 genomes from taxonomically diverse fungi highlighted a generally widespread,
      but discontinuous, distribution of ZtGT2 orthologues, and a complete absence of
      any similar proteins in non-filamentous ascomycete yeasts. Deletion mutants of
      the ZtGT2 orthologue in the taxonomically un-related fungus Fusarium graminearum
      were also severely impaired in hyphal growth and non-pathogenic on wheat ears.
      ZtGT2 expression increased during filamentous growth and electron microscopy on
      deletion mutants (DeltaZtGT2) suggested the protein functions to maintain the
      outermost surface of the fungal cell wall. Despite this, adhesion to leaf
      surfaces was unaffected in DeltaZtGT2 mutants and global RNAseq-based gene
      expression profiling highlighted that surface-sensing and protein secretion was
      also largely unaffected. However, DeltaZtGT2 mutants constitutively overexpressed
      several transmembrane and secreted proteins, including an important LysM-domain
      chitin-binding virulence effector, Zt3LysM. ZtGT2 likely functions in the
      synthesis of a currently unknown, potentially minor but widespread, extracellular
      or outer cell wall polysaccharide which plays a key role in facilitating many
      interactions between plants and fungi by enabling hyphal growth on solid
      matrices.

PMID- 29020040
TI  - Validity and reliability of the Dutch version of the Copenhagen Hip And Groin
      Outcome Score (HAGOS-NL) in patients with hip pathology.
AB  - BACKGROUND AND OBJECTIVES: The Copenhagen Hip And Groin Outcome Score (HAGOS) was
      developed to assess disease-specific consequences in young to middle-aged,
      physically active hip and/or groin patients. The study aimed to determine
      validity and reliability of the Dutch version of the HAGOS (HAGOS-NL) for middle
      aged patients with hip complaints. DESIGN AND METHODS: To assess validity, 117
      participants completed five questionnaires: HAGOS-NL, international Hip Outcome
      Tool (iHOT-12NL), Hip disability and Osteoarthritis Outcome Score (HOOS), RAND-36
      Health Survey and Tegner activity scale. Structural validity was determined by
      conducting confirmatory factor analysis. Construct validity was analyzed by
      formulating predefined hypotheses regarding relationships between the HAGOS-NL
      and subscales of the iHOT-12NL, HOOS, RAND-36 and Tegner activity scale. The
      HAGOS-NL was filled out again by 67 patients to explore test-retest reliability.
      Reliability was assessed in terms of Cronbach's alpha, Intraclass Correlation
      Coefficient (ICC), Standard Error of Measurement (SEM) and Minimal Detectable
      Change (MDC). The Bland and Altman method was used to explore absolute agreement.
      RESULTS: Factor analysis confirmed that the HAGOS-NL consists of six subscales.
      All hypotheses were confirmed, indicating good construct validity. Internal
      consistency was good, with Cronbach's alpha values ranging from 0.89 to 0.98.
      Test-retest reliability was considered good, with ICC values of 0.80 and higher.
      The SEM ranged from 6.6 to 12.3, and MDC at individual level from 18.3 to 34.1
      and at group level from 2.3 to 4.4. Bland and Altman analyses showed no bias.
      CONCLUSION: The HAGOS-NL is a reliable and valid instrument for measuring pain,
      physical functioning and quality of life in middle-aged patients with hip
      complaints.

PMID- 29020039
TI  - ERalpha36, a variant of estrogen receptor alpha, is predominantly localized in
      mitochondria of human uterine smooth muscle and leiomyoma cells.
AB  - ERalpha36 is a naturally occurring, membrane-associated, isoform of estrogen
      receptor alpha. The expression of ERalpha36 is due to alternative splicing and
      different promoter usage. ERalpha36 is a dominant-negative effector of ERalpha66
      mediated transactivational activities and has the potential to trigger membrane
      initiated mitogenic, nongenomic, estrogen signaling; however, the subcellular
      localization of ERalpha36 remains controversial. To determine the cellular
      localization of ERalpha36 in estrogen-responsive human uterine smooth muscle (ht
      UtSMC) and leiomyoma (fibroid; ht-UtLM) cells, we conducted systematic confocal
      microscopy and subcellular fractionation analysis using ERalpha36 antibodies.
      With Image J colocalizaton analysis plugin, confocal images were analyzed to
      obtain a Pearson's Correlation Coefficient (PCC) to quantify signal
      colocalization of ERalpha36 with mitochondrial, endoplasmic reticulum, and
      cytoskeletal components in both cell lines. When cells were double-stained with
      an ERalpha36 antibody and a mitochondrial-specific dye, MitoTracker, the PCC for
      the two channel signals were both greater than 0.75, indicating strong
      correlation between ERalpha36 and mitochondrial signals in the two cell lines. A
      blocking peptide competition assay confirmed that the mitochondria-associated
      ERalpha36 signal detected by confocal analysis was specific for ERalpha36. In
      contrast, confocal images double-stained with an ERalpha36 antibody and
      endoplasmic reticulum or cytoskeletal markers, had PCCs that were all less than
      0.4, indicating no or very weak signal correlation. Fractionation studies showed
      that ERalpha36 existed predominantly in membrane fractions, with minimal or
      undetected amounts in the cytosol, nuclear, chromatin, and cytoskeletal
      fractions. With isolated mitochondrial preparations, we confirmed that a known
      mitochondrial protein, prohibitin, was present in mitochondria, and by co
      immunoprecipitation analysis that ERalpha36 was associated with prohibitin in ht
      UtLM cells. The distinctive colocalization pattern of ERalpha36 with mitochondria
      in ht-UtSMC and ht-UtLM cells, and the association of ERalpha36 with a
      mitochondrial-specific protein suggest that ERalpha36 is localized primarily in
      mitochondria and may play a pivotal role in non-genomic signaling and
      mitochondrial functions.

PMID- 29020041
TI  - How will climate change pathways and mitigation options alter incidence of vector
      borne diseases? A framework for leishmaniasis in South and Meso-America.
AB  - The enormous global burden of vector-borne diseases disproportionately affects
      poor people in tropical, developing countries. Changes in vector-borne disease
      impacts are often linked to human modification of ecosystems as well as climate
      change. For tropical ecosystems, the health impacts of future environmental and
      developmental policy depend on how vector-borne disease risks trade off against
      other ecosystem services across heterogeneous landscapes. By linking future socio
      economic and climate change pathways to dynamic land use models, this study is
      amongst the first to analyse and project impacts of both land use and climate
      change on continental-scale patterns in vector-borne diseases. Models were
      developed for cutaneous and visceral leishmaniasis in the Americas-ecologically
      complex sand fly borne infections linked to tropical forests and diverse wild and
      domestic mammal hosts. Both diseases were hypothesised to increase with available
      interface habitat between forest and agricultural or domestic habitats and with
      mammal biodiversity. However, landscape edge metrics were not important as
      predictors of leishmaniasis. Models including mammal richness were similar in
      accuracy and predicted disease extent to models containing only climate and land
      use predictors. Overall, climatic factors explained 80% and land use factors only
      20% of the variance in past disease patterns. Both diseases, but especially
      cutaneous leishmaniasis, were associated with low seasonality in temperature and
      precipitation. Since such seasonality increases under future climate change,
      particularly under strong climate forcing, both diseases were predicted to
      contract in geographical extent to 2050, with cutaneous leishmaniasis contracting
      by between 35% and 50%. Whilst visceral leishmaniasis contracted slightly more
      under strong than weak management for carbon, biodiversity and ecosystem
      services, future cutaneous leishmaniasis extent was relatively insensitive to
      future alternative socio-economic pathways. Models parameterised at narrower
      geographical scales may be more sensitive to land use pattern and project more
      substantial changes in disease extent under future alternative socio-economic
      pathways.

PMID- 29020044
TI  - Correction: Do MZ twins have discordant experiences of friendship? A qualitative
      hypothesis-generating MZ twin differences study.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0180521.].

PMID- 29020042
TI  - Is mass drug administration against lymphatic filariasis required in urban
      settings? The experience in Kano, Nigeria.
AB  - BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF),
      launched in 2000, has the target of eliminating the disease as a public health
      problem by the year 2020. The strategy adopted is mass drug administration (MDA)
      to all eligible individuals in endemic communities and the implementation of
      measures to reduce the morbidity of those suffering from chronic disease. Success
      has been recorded in many rural endemic communities in which elimination efforts
      have centered. However, implementation has been challenging in several urban
      African cities. The large cities of West Africa, exemplified in Nigeria in Kano
      are challenging for LF elimination program because reaching 65% therapeutic
      coverage during MDA is difficult. There is therefore a need to define a strategy
      which could complement MDA. Thus, in Kano State, Nigeria, while LF MDA had
      reached 33 of the 44 Local Government Areas (LGAs) there remained eleven 'urban'
      LGAs which had not been covered by MDA. Given the challenges of achieving at
      least 65% coverage during MDA implementation over several years in order to
      achieve elimination, it may be challenging to eliminate LF in such settings. In
      order to plan the LF control activities, this study was undertaken to confirm the
      LF infection prevalence in the human and mosquito populations in three urban
      LGAs. METHODS: The prevalence of circulating filarial antigen (CFA) of Wuchereria
      bancrofti was assessed by an immuno-chromatography test (ICT) in 981 people in
      three urban LGAs of Kano state, Nigeria. Mosquitoes were collected over a period
      of 4 months from May to August 2015 using exit traps, gravid traps and pyrethrum
      knock-down spray sheet collections (PSC) in different households. A proportion of
      mosquitoes were analyzed for W. bancrofti, using dissection, loop-mediated
      isothermal amplification (LAMP) assay and conventional polymerase chain reaction
      (PCR). RESULTS: The results showed that none of the 981 subjects (constituted of
      <21% of children 5-10 years old) tested had detectable levels of CFA in their
      blood. Entomological results showed that An. gambiae s.l. had W. bancrofti DNA
      detectable in pools in Kano; W. bancrofti DNA was detected in between 0.96% and
      6.78% and to a lesser extent in Culex mosquitoes where DNA was detected at rates
      of between 0.19% and 0.64%. DNA analysis showed that An. coluzzii constituted
      9.9% of the collected mosquitoes and the remaining 90.1% of the mosquitoes were
      Culex mosquitoes. CONCLUSION: Despite detection of W. bancrofti DNA within
      mosquito specimens collected in three Kano urban LGAs, we were not able to find a
      subject with detectable level of CFA. Together with other evidence suggesting
      that LF transmission in urban areas in West Africa may not be of significant
      importance, the Federal Ministry of Health advised that two rounds of MDA be
      undertaken in the urban areas of Kano. It is recommended that the prevalence of
      W. bancrofti infection in the human and mosquito populations be re-assessed after
      a couple of years.

PMID- 29020043
TI  - Chloroplast digestion and the development of functional kleptoplasty in juvenile
      Elysia timida (Risso, 1818) as compared to short-term and non-chloroplast
      retaining sacoglossan slugs.
AB  - Sacoglossan sea slugs are the only metazoans known to perform functional
      kleptoplasty, the sequestration and retention of functional chloroplasts within
      their digestive gland cells. Remarkably, a few species with this ability can
      survive starvation periods of 3-12 months likely due to their stolen
      chloroplasts. There are no reports of kleptoplast transfer from mother slug to
      either eggs or juveniles, demonstrating that each animal must independently
      acquire its kleptoplasts and develop the ability to maintain them within its
      digestive gland. We present here an investigation into the development of
      functional kleptoplasty in a long-term kleptoplast retaining species, Elysia
      timida. Laboratory-reared juvenile slugs of different post-metamorphic ages were
      placed in starvation and compared to 5 known short-term retaining slug species
      and 5 non-retaining slug species. The subsequent results indicate that functional
      kleptoplasty is not performed by E. timida until after 15 days post-metamorphosis
      and that by 25 days, these animals outlive many of the short-term retention
      species. Digestive activity was also monitored using lysosomal abundance as an
      indicator, revealing different patterns in starving juveniles versus adults.
      Starved juveniles were reintroduced to food to determine any differences in
      digestive activity when starvation ends, resulting in an increase in the number
      of kleptoplasts, but no overall change in lysosomal activity. By revealing some
      of the changes that occur during early development in these animals, which begin
      as non-kleptoplast-retaining and grow into long-term retaining slugs, this
      investigation provides a basis for future inquiries into the origin and
      development of this remarkable ability.

PMID- 29020045
TI  - Human amnion-derived mesenchymal stem cells promote osteogenic and angiogenic
      differentiation of human adipose-derived stem cells.
AB  - Tissue engineering using suitable mesenchymal stem cells (MSCs) shows great
      potential to regenerate bone defects. Our previous studies have indicated that
      human amnion-derived mesenchymal stem cells (HAMSCs) could promote the osteogenic
      differentiation of human bone marrow mesenchymal stem cells (HBMSCs). Human
      adipose-derived stem cells (HASCs), obtained from adipose tissue in abundance,
      are capable of multi-lineage differentiation. In this study, the effects of
      HAMSCs on osteogenic and angiogenic differentiation of HASCs were systematically
      investigated. Proliferation levels were measured by flow cytometry. Osteoblastic
      differentiation and mineralization were investigated using chromogenic alkaline
      phosphatase activity (ALP) activity substrate assays, Alizarin red S staining,
      real-time polymerase chain reaction (real-time PCR) analysis of osteogenic marker
      expression, and Western blotting. We found that HAMSCs increased the
      proliferation and osteoblastic differentiation of HASCs. Moreover, enzyme-linked
      immunosorbent assay (ELISA) and human umbilical vein endothelial cells (HUVECs)
      tube formation suggested HAMSCs enhanced angiogenic potential of HASCs via
      secretion of increased vascular endothelial growth factor (VEGF). Thus, we
      conclude that HAMSC might be a valuable therapeutic approach to promote HASCs
      involved bone regeneration.

PMID- 29020048
TI  - Correction: The complex dynamics of products and its asymptotic properties.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0177360.].

PMID- 29020047
TI  - Correlates of institutional deliveries among teenage and non-teenage mothers in
      Nepal.
AB  - INTRODUCTION: Globally, maternal age is identified as an important predictor of
      institutional service utilization during delivery. This study aims to assess the
      correlates of institutional delivery among teenage and non-teenage mothers in
      Nepal by using the data from Nepal Demographic and Health Survey 2011. METHODS:
      The study population consisted of 5391 women of reproductive age (15-49 years)
      who had given birth to a child within five years before the survey. Out of them,
      381 (7.07%) were teenage mothers. The association between the background
      characteristics and institutional delivery was assessed separately for the
      teenage and non-teenage mothers using chi-square test and multiple logistic
      regression analysis. RESULTS: After adjusting for background characteristics,
      teenage mothers were found more likely to deliver at a health facility [AOR:
      2.25; 95% CI: 1.10 4.59] in comparison to the non-teenage mothers. Place of
      residence, occupation, socioeconomic status, and frequency of ANC visits were
      associated with institutional delivery in both the teenage and non-teenage
      mothers. However, educational status, parity, birth preparedness and women
      autonomy had statistically significant association with institutional delivery
      among the non-teenage mothers only. None of the background characteristics were
      significantly associated with institutional delivery in teenage mothers only.
      CONCLUSIONS: This study identified a significant difference in institutional
      delivery service utilization among the teenage and non-teenage mothers. While the
      association of most of the background characteristics with institutional delivery
      was uniform for both teenage and non-teenage mothers, the association with
      educational status, parity, birth preparedness and women autonomy was significant
      only for non-teenage mothers. Considering this difference in the interaction of
      women's background characteristics with institutional delivery between teenage
      and non-teenage mothers might help in identifying the pain points and devise
      targeted interventions to encourage institutional delivery in teenage mothers or
      non-teenage mothers or both.

PMID- 29020046
TI  - Mid-infrared spectroscopy of serum, a promising non-invasive method to assess
      prognosis in patients with ascites and cirrhosis.
AB  - BACKGROUND & AIMS: Prognostic tests are critical in the management of patients
      with cirrhosis and ascites. Biological tests or scores perform poorly in that
      situation. Mid-infrared fibre evanescent wave spectroscopy (MIR-FEWS) which
      allows for global serum metabolic profiling may provide more relevant information
      by measuring a wider range of metabolic parameters in serum. Here we present the
      accuracy of a MIR-FEWS based predictive model for the prognosis of 6 months
      survival in patients with ascites and cirrhosis. METHODS: Patients with ascites
      were prospectively included and followed up for 6 months. MIR-FEWS spectra were
      measured in serum samples. The most informative spectral variables obtained by
      MIR-FEWS were selected by FADA algorithm and then used to build the MIR model.
      Accuracy of this model was assessed by ROC curves and 90%/10% Monte Carlo cross
      validation. MIR model accuracy for 6 months survival was compared to that of the
      Child-Pugh and MELD scores. RESULTS: 119 patients were included. The mean age was
      57.36+/-13.70, the MELD score was 16.32+/-6.26, and the Child-Pugh score was
      9.5+/-1.83. During follow-up, 23 patients died (20%). The MIR model had an AUROC
      for 6 months mortality of 0.90 (CI95: 0.88-0.91), the MELD 0.77 (CI95: 0.66-0.89)
      and Child-Pugh 0.76 (CI95: 0.66-0.88). MELD and Child-Pugh AUROCs were
      significantly lower than that of the MIR model (p = 0.02 and p = 0.02
      respectively). Multivariate logistic regression analysis showed that MELD
      (p<0.05, OR:0.86;CI95:0.76-0.97), Beta blockers (p = 0.036;OR:0.20;CI95:0.04
      0.90), and the MIR model (p<0.001; OR:0.50; CI95:0.37-0.66), were significantly
      associated with 6 months mortality. CONCLUSIONS: In this pilot study MIR-FEWS
      more accurately assess the 6-month prognosis of patients with ascites and
      cirrhosis than the MELD or Child-Pugh scores. These promising results, if
      confirmed by a larger study, suggest that mid infrared spectroscopy could be
      helpful in the management of these patients.

PMID- 29020049
TI  - Further insight into genetic variation and haplotype diversity of Cherry virus A
      from China.
AB  - Cherry virus A (CVA) infection appears to be prevalent in cherry plantations
      worldwide. In this study, the diversity of CVA isolates from 31 cherry samples
      collected from different orchards around Bohai Bay in northeastern China was
      analyzed. The complete genome of one of these isolates, ChYT52, was found to be
      7,434 nt in length excluding the poly (A) tail. It shares between 79.9-98.7%
      identity with CVA genome sequences in GenBank, while its RdRp core is more
      divergent (79.1-90.7% nt identity), likely as a consequence of a recombination
      event. Phylogenetic analysis of ChYT52 genome with CVA genomes in Genbank
      resulted in at least 7 major clusters plus additional 5 isolates alone at the end
      of long branches suggesting the existence of further phylogroups diversity in
      CVA. The genetic diversity of Chinese CVA isolates from 31 samples and GenBank
      sequences were analyzed in three genomic regions that correspond to the coat
      protein, the RNA-dependent RNA polymerase core region, and the movement protein
      genes. With few exceptions likely representing further recombination impact, the
      trees various trees are largely congruent, indicating that each region provides
      valuable phylogenetic information. In all cases, the majority of the Chinese CVA
      isolates clustering in phylogroup I, together with the X82547 reference sequence
      from Germany. Statistically significant negative values were obtained for
      Tajima's D in the three genes for phylogroup I, suggesting that it may be
      undergoing a period of expansion. There was considerable haplotype diversity in
      the individual samples and more than half samples contained genetically diverse
      haplotypes belonging to different phylogroups. In addition, a number of
      statistically significant recombination events were detected in CVA genomes or in
      the partial genomic sequences indicating an important contribution of
      recombination to CVA evolution. This work provides a foundation for elucidation
      of the epidemiological characteristics and evolutionary history of CVA
      populations.

PMID- 29020050
TI  - Correction: Notch Ligand Delta-Like 4-Pretreated Dendritic Cells Alleviate
      Allergic Airway Responses by Enhancing IL-10 Production.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0063613.].

PMID- 29020052
TI  - Effects of socioeconomic status on esophageal adenocarcinoma stage at diagnosis,
      receipt of treatment, and survival: A population-based cohort study.
AB  - The incidence of esophageal adenocarcinoma (EAC) is increasing worldwide and has
      overtaken squamous histology in occurrence. We studied the impact of
      socioeconomic status (SES) on EAC stage at diagnosis, receipt of treatment, and
      survival. A population-based retrospective cohort study was conducted using
      Ontario Cancer Registry-linked administrative health data. Multinomial logistic
      regression was used to examine the association between SES (income quintile) and
      stage at EAC diagnosis and EAC treatment. Survival times following EAC diagnosis
      were estimated using Kaplan-Meier method. Cox proportional-hazards regression
      analysis was used to examine the association between SES and EAC survival.
      Between 2003-2012, 2,125 EAC cases were diagnosed. Median survival for the lowest
      SES group was 10.9 months compared to 11.6 months for the highest-SES group; the
      5-year survival was 9.8% vs. 15.0%. Compared to individuals in the highest-SES
      group, individuals in the lowest-SES category experienced no significant
      difference in EAC treatment (91.6% vs. 93.3%, P = 0.314) and deaths (78.9% vs.
      75.6%, P = 0.727). After controlling for covariates, no significant associations
      were found between SES and cancer stage at diagnosis and EAC treatment.
      Additionally, after controlling for age, gender, urban/rural residence, birth
      country, health region, aggregated diagnosis groups, cancer stage, treatment, and
      year of diagnosis, no significant association was found between SES and EAC
      survival. Moreover, increased mortality risk was observed among those with older
      age (P = 0.001), advanced-stage of EAC at diagnosis (P < 0.001), and those
      receiving chemotherapy alone, radiotherapy alone, or surgery plus chemotherapy (P
      < 0.001). Adjusted proportional-hazards model findings suggest that there is no
      association between SES and EAC survival. While the unadjusted model suggests
      reduced survival among individuals in lower income quintiles, this is no longer
      significant after adjusting for any covariate. Additionally, there is an apparent
      association between SES and survival when considering only those individuals
      diagnosed with stage 0-III EAC. These analyses suggest that the observed direct
      relationship between SES and survival is explained by patient-level factors
      including receipt of treatment, something that is potentially modifiable.

PMID- 29020053
TI  - Method for measuring tri-axial lumbar motion angles using wearable sheet stretch
      sensors.
AB  - BACKGROUND: Body movements, such as trunk flexion and rotation, are risk factors
      for low back pain in occupational settings, especially in healthcare workers.
      Wearable motion capture systems are potentially useful to monitor lower back
      movement in healthcare workers to help avoid the risk factors. In this study, we
      propose a novel system using sheet stretch sensors and investigate the system
      validity for estimating lower back movement. METHODS: Six volunteers (female:male
      = 1:1, mean age: 24.8 +/- 4.0 years, height 166.7 +/- 5.6 cm, weight 56.3 +/- 7.6
      kg) participated in test protocols that involved executing seven types of
      movements. The movements were three uniaxial trunk movements (i.e., trunk flexion
      extension, trunk side-bending, and trunk rotation) and four multiaxial trunk
      movements (i.e., flexion + rotation, flexion + side-bending, side-bending +
      rotation, and moving around the cranial-caudal axis). Each trial lasted for
      approximately 30 s. Four stretch sensors were attached to each participant's
      lower back. The lumbar motion angles were estimated using simple linear
      regression analysis based on the stretch sensor outputs and compared with those
      obtained by the optical motion capture system. RESULTS: The estimated lumbar
      motion angles showed a good correlation with the actual angles, with correlation
      values of r = 0.68 (SD = 0.35), r = 0.60 (SD = 0.19), and r = 0.72 (SD = 0.18)
      for the flexion-extension, side bending, and rotation movements, respectively
      (all P < 0.05). The estimation errors in all three directions were less than 3
      degrees . CONCLUSION: The stretch sensors mounted on the back provided reasonable
      estimates of the lumbar motion angles. The novel motion capture system provided
      three directional angles without capture space limits. The wearable system
      possessed great potential to monitor the lower back movement in healthcare
      workers and helping prevent low back pain.

PMID- 29020054
TI  - A novel approach for automatic visualization and activation detection of evoked
      potentials induced by epidural spinal cord stimulation in individuals with spinal
      cord injury.
AB  - Voluntary movements and the standing of spinal cord injured patients have been
      facilitated using lumbosacral spinal cord epidural stimulation (scES).
      Identifying the appropriate stimulation parameters (intensity, frequency and
      anode/cathode assignment) is an arduous task and requires extensive mapping of
      the spinal cord using evoked potentials. Effective visualization and detection of
      muscle evoked potentials induced by scES from the recorded electromyography (EMG)
      signals is critical to identify the optimal configurations and the effects of
      specific scES parameters on muscle activation. The purpose of this work was to
      develop a novel approach to automatically detect the occurrence of evoked
      potentials, quantify the attributes of the signal and visualize the effects
      across a high number of scES parameters. This new method is designed to automate
      the current process for performing this task, which has been accomplished
      manually by data analysts through observation of raw EMG signals, a process that
      is laborious and time-consuming as well as prone to human errors. The proposed
      method provides a fast and accurate five-step algorithms framework for activation
      detection and visualization of the results including: conversion of the EMG
      signal into its 2-D representation by overlaying the located signal building
      blocks; de-noising the 2-D image by applying the Generalized Gaussian Markov
      Random Field technique; detection of the occurrence of evoked potentials using a
      statistically optimal decision method through the comparison of the probability
      density functions of each segment to the background noise utilizing log
      likelihood ratio; feature extraction of detected motor units such as peak-to-peak
      amplitude, latency, integrated EMG and Min-max time intervals; and finally
      visualization of the outputs as Colormap images. In comparing the automatic
      method vs. manual detection on 700 EMG signals from five individuals, the new
      approach decreased the processing time from several hours to less than 15 seconds
      for each set of data, and demonstrated an average accuracy of 98.28% based on the
      combined false positive and false negative error rates. The sensitivity of this
      method to the signal-to-noise ratio (SNR) was tested using simulated EMG signals
      and compared to two existing methods, where the novel technique showed much lower
      sensitivity to the SNR.

PMID- 29020051
TI  - A combination of plasma phospholipid fatty acids and its association with
      incidence of type 2 diabetes: The EPIC-InterAct case-cohort study.
AB  - BACKGROUND: Combinations of multiple fatty acids may influence cardiometabolic
      risk more than single fatty acids. The association of a combination of fatty
      acids with incident type 2 diabetes (T2D) has not been evaluated. METHODS AND
      FINDINGS: We measured plasma phospholipid fatty acids by gas chromatography in
      27,296 adults, including 12,132 incident cases of T2D, over the follow-up period
      between baseline (1991-1998) and 31 December 2007 in 8 European countries in EPIC
      InterAct, a nested case-cohort study. The first principal component derived by
      principal component analysis of 27 individual fatty acids (mole percentage) was
      the main exposure (subsequently called the fatty acid pattern score [FA-pattern
      score]). The FA-pattern score was partly characterised by high concentrations of
      linoleic acid, stearic acid, odd-chain fatty acids, and very-long-chain saturated
      fatty acids and low concentrations of gamma-linolenic acid, palmitic acid, and
      long-chain monounsaturated fatty acids, and it explained 16.1% of the overall
      variability of the 27 fatty acids. Based on country-specific Prentice-weighted
      Cox regression and random-effects meta-analysis, the FA-pattern score was
      associated with lower incident T2D. Comparing the top to the bottom fifth of the
      score, the hazard ratio of incident T2D was 0.23 (95% CI 0.19-0.29) adjusted for
      potential confounders and 0.37 (95% CI 0.27-0.50) further adjusted for metabolic
      risk factors. The association changed little after adjustment for individual
      fatty acids or fatty acid subclasses. In cross-sectional analyses relating the FA
      pattern score to metabolic, genetic, and dietary factors, the FA-pattern score
      was inversely associated with adiposity, triglycerides, liver enzymes, C-reactive
      protein, a genetic score representing insulin resistance, and dietary intakes of
      soft drinks and alcohol and was positively associated with high-density
      lipoprotein cholesterol and intakes of polyunsaturated fat, dietary fibre, and
      coffee (p < 0.05 each). Limitations include potential measurement error in the
      fatty acids and other model covariates and possible residual confounding.
      CONCLUSIONS: A combination of individual fatty acids, characterised by high
      concentrations of linoleic acid, odd-chain fatty acids, and very long-chain fatty
      acids, was associated with lower incidence of T2D. The specific fatty acid
      pattern may be influenced by metabolic, genetic, and dietary factors.

PMID- 29020055
TI  - Danshen protects against early-stage alcoholic liver disease in mice via inducing
      PPARalpha activation and subsequent 4-HNE degradation.
AB  - Alcoholic liver disease (ALD) is a type of chronic liver disease caused by long
      term heavy ethanol consumption. Danshen is one of the most commonly used
      substances in traditional Chinese medicine and has been widely used for the
      treatment of various diseases, and most frequently, the ALD. The current study
      aims to determine the potential beneficial effect of Danshen administration on
      ALD and to clarify the underlying molecular mechanisms. Danshen administration
      improved liver pathologies of ALD, attenuated alcohol-induced increment of
      hepatic 4-Hydroxynonenal (4-HNE) formation, and prevented hepatic Peroxisome
      proliferators activated receptor alpha (PPARalpha) suppression in response to
      chronic alcohol consumption. Cell culture studies revealed that both
      hepatoprotective effect and increased intracellular 4-HNE clearance instigated by
      Danshen supplementation are PPARalpha-dependent. In conclusion, Danshen
      administration can protect against ALD via inducing PPARalpha activation and
      subsequent 4-HNE degradation.

PMID- 29020056
TI  - Differences in change blindness to real-life scenes in adults with autism
      spectrum conditions.
AB  - People often fail to detect large changes to visual scenes following a brief
      interruption, an effect known as 'change blindness'. People with autism spectrum
      conditions (ASC) have superior attention to detail and better discrimination of
      targets, and often notice small details that are missed by others. Together these
      predict people with autism should show enhanced perception of changes in simple
      change detection paradigms, including reduced change blindness. However, change
      blindness studies to date have reported mixed results in ASC, which have
      sometimes included no differences to controls or even enhanced change blindness.
      Attenuated change blindness has only been reported to date in ASC in children and
      adolescents, with no study reporting reduced change blindness in adults with ASC.
      The present study used a change blindness flicker task to investigate the
      detection of changes in images of everyday life in adults with ASC (n = 22) and
      controls (n = 22) using a simple change detection task design and full range of
      original scenes as stimuli. Results showed the adults with ASC had reduced change
      blindness compared to adult controls for changes to items of marginal interest in
      scenes, with no group difference for changes to items of central interest. There
      were no group differences in overall response latencies to correctly detect
      changes nor in the overall number of missed detections in the experiment.
      However, the ASC group showed greater missed changes for marginal interest
      changes of location, showing some evidence of greater change blindness as well.
      These findings show both reduced change blindness to marginal interest changes in
      ASC, based on response latencies, as well as greater change blindness to changes
      of location of marginal interest items, based on detection rates. The findings of
      reduced change blindness are consistent with clinical reports that people with
      ASC often notice small changes to less salient items within their environment,
      and are in-line with theories of enhanced local processing and greater attention
      to detail in ASC. The findings of lower detection rates for one of the marginal
      interest conditions may be related to problems in shifting attention or an overly
      focused attention spotlight.

PMID- 29020057
TI  - High dose teriparatide (rPTH1-34) therapy increases callus volume and enhances
      radiographic healing at 8-weeks in a massive canine femoral allograft model.
AB  - Small animal studies have demonstrated significant high-dose recombinant
      parathyroid hormone1-34 (rPTH1-34) effects on intercalary allograft healing.
      Towards a human adjuvant therapy to decrease non-unions, we evaluated rPTH1-34
      safety and efficacy in a clinically relevant canine femoral allograft model.
      Adult female mongrel hounds (n = 20) received a 5cm mid-diaphyseal osteotomy
      reconstructed with a plated allograft, and were randomized to: 1) Placebo (n = 5;
      daily saline), 2) Continuous rPTH1-34 (n = 7; 5 MUg/kg/day s.c. from day 1-55
      post-op), or 3) Delayed rPTH1-34 (n = 8; 5 MUg/kg/day s.c. from day 14-28 post
      op). Safety was assessed by physical behavior and blood calcium monitoring. Cone
      beam CT (CB-CT) was performed on days 14, 28 and 56 post-op to assess 2D cortical
      healing, 3D bone volume, and Union Ratio. Biomechanical testing and dynamic
      histomorphometry were also performed. The high drug dose was poorly tolerated, as
      most dogs receiving rPTH1-34 had to be given intravenous saline, and one dog died
      from hypercalcemia. Continuous rPTH1-34 significantly increased 2D healing and
      callus volumes at 4-weeks versus Placebo, and sustained the significant increase
      in cortical union at 8-week (p<0.05). These rPTH1-34 effects were confirmed by
      histomorphometry, revealing significant increases in mineral apposition rates
      (MAR) on host bone and graft-host junctions (p<0.05). Delayed rPTH1-34
      significantly increased callus volume and MAR at 8 weeks (p<0.05). Although no
      biomechanical differences were observed, as expected for early healing, the
      results demonstrated that 2D RUST scoring significantly correlated with torsional
      biomechanics (p<0.01). In conclusion, 8-weeks of intermittent high-dose rPTH1-34
      treatment significantly increases callus formation and accelerates bony union of
      intercalary massive allografts in a clinically relevant canine model, but with
      serious side-effects from hypercalcemia.

PMID- 29020058
TI  - HIV transmitted/founder vaccines elicit autologous tier 2 neutralizing antibodies
      for the CD4 binding site.
AB  - Here we report the construction, antigenicity and initial immunogenicity testing
      of DNA and modified vaccinia Ankara (MVA) vaccines expressing virus-like
      particles (VLPs) displaying sequential clade C Envelopes (Envs) that co-evolved
      with the elicitation of broadly neutralizing antibodies (bnAbs) to the CD4
      binding site (CD4bs) in HIV-infected individual CH0505. The VLP-displayed Envs
      showed reactivity for conformational epitopes displayed on the receptor-binding
      form of Env. Two inoculations of the DNA-T/F vaccine, followed by 3 inoculations
      of the MVA-T/F vaccine and a final inoculation of the MVA-T/F plus a gp120-T/F
      protein vaccine elicited nAb to the T/F virus in 2 of 4 rhesus macaques (ID50 of
      ~175 and ~30). Neutralizing Ab plateaued at 100% neutralization and mapped to the
      CD4bs like the bnAbs elicited in CH0505. The nAb did not have breadth for other
      tier 2 viruses. Immunizations with T/F followed by directed-lineage vaccines,
      both with and without co-delivery of directed-lineage gp120 boosts, failed to
      elicit tier 2 neutralizing Ab for the CD4bs. Thus, pulsed exposures to DNA and
      MVA-expressed VLPs plus gp120 protein of a T/F Env can induce autologous tier 2
      nAbs to the CD4bs.

PMID- 29020059
TI  - The relation between face-emotion recognition and social function in adolescents
      with autism spectrum disorders: A case control study.
AB  - An altered processing of emotions may contribute to a reduced ability for social
      interaction and communication in autism spectrum disorder, ASD. We investigated
      how face-emotion recognition in ASD is different from typically developing across
      adolescent age groups. Fifty adolescents diagnosed with ASD and 49 typically
      developing (age 12-21 years) were included. The ASD diagnosis was underpinned by
      parent-rated Social Communication Questionnaire. We used a cued GO/ NOGO task
      with pictures of facial expressions and recorded reaction time, intra-individual
      variability of reaction time and omissions/commissions. The Social Responsiveness
      Scale was used as a measure of social function. Analyses were conducted for the
      whole group and for young (< 16 years) and old (>= 16 years) age groups. We found
      no significant differences in any task measures between the whole group of
      typically developing and ASD and no significant correlations with the Social
      Responsiveness Scale. However, there was a non-significant tendency for longer
      reaction time in the young group with ASD (p = 0.099). The Social Responsiveness
      Scale correlated positively with reaction time (r = 0.30, p = 0.032) and intra
      individual variability in reaction time (r = 0.29, p = 0.037) in the young group
      and in contrast, negatively in the old group (r = -0.23, p = 0.13; r = -0.38, p =
      0.011, respectively) giving significant age group interactions for both reaction
      time (p = 0.008) and intra-individual variability in reaction time (p = 0.001).
      Our findings suggest an age-dependent association between emotion recognition and
      severity of social problems indicating a delayed development of emotional
      understanding in ASD. It also points towards alterations in top-down attention
      control in the ASD group. This suggests novel disease-related features that
      should be investigated in more details in experimental settings.

PMID- 29020060
TI  - Phosphatidylinositol-4,5-bisphosphate is required for KCNQ1/KCNE1 channel
      function but not anterograde trafficking.
AB  - The slow delayed-rectifier potassium current (IKs) is crucial for human cardiac
      action potential repolarization. The formation of IKs requires co-assembly of the
      KCNQ1 alpha-subunit and KCNE1 beta-subunit, and mutations in either of these
      subunits can lead to hereditary long QT syndrome types 1 and 5, respectively. It
      is widely recognised that the KCNQ1/KCNE1 (Q1/E1) channel requires
      phosphatidylinositol-4,5-bisphosphate (PIP2) binding for function. We previously
      identified a cluster of basic residues in the proximal C-terminus of KCNQ1 that
      form a PIP2/phosphoinositide binding site. Upon charge neutralisation of these
      residues we found that the channel became more retained in the endoplasmic
      reticulum, which raised the possibility that channel-phosphoinositide
      interactions could play a role in channel trafficking. To explore this further we
      used a chemically induced dimerization (CID) system to selectively deplete PIP2
      and/or phosphatidylinositol-4-phosphate (PI(4)P) at the plasma membrane (PM) or
      Golgi, and we subsequently monitored the effects on both channel trafficking and
      function. The depletion of PIP2 and/or PI(4)P at either the PM or Golgi did not
      alter channel cell-surface expression levels. However, channel function was
      extremely sensitive to the depletion of PIP2 at the PM, which is in contrast to
      the response of other cardiac potassium channels tested (Kir2.1 and Kv11.1).
      Surprisingly, when using the CID system IKs was dramatically reduced even before
      dimerization was induced, highlighting limitations regarding the utility of this
      system when studying processes highly sensitive to PIP2 depletion. In conclusion,
      we identify that the Q1/E1 channel does not require PIP2 or PI(4)P for
      anterograde trafficking, but is heavily reliant on PIP2 for channel function once
      at the PM.

PMID- 29020062
TI  - Seasonal and circadian biases in bird tracking with solar GPS-tags.
AB  - Global Positioning System (GPS) tags are nowadays widely used in wildlife
      tracking. This geolocation technique can suffer from fix loss biases due to poor
      satellite GPS geometry, that result in tracking data gaps leading to wrong
      research conclusions. In addition, new solar-powered GPS tags deployed on birds
      can suffer from a new "battery drain bias" currently ignored in movement ecology
      analyses. We use a GPS tracking dataset of bearded vultures (Gypaetus barbatus),
      tracked for several years with solar GPS tags, to evaluate the causes and
      triggers of fix and data retrieval loss biases. We compare two models of solar
      GPS tags using different data retrieval systems (Argos vs GSM-GPRS), and
      programmed with different duty cycles. Neither of the models was able to
      accomplish the duty cycle programed initially. Fix and data retrieval loss rates
      were always greater than expected, and showed non-random gaps in GPS locations.
      Number of fixes per month of tracking was a bad criterion to identify tags with
      smaller biases. Fix-loss rates were four times higher due to battery drain than
      due to poor GPS satellite geometry. Both tag models were biased due to the uneven
      solar energy available for the recharge of the tag throughout the annual cycle,
      resulting in greater fix-loss rates in winter compared to summer. In addition, we
      suggest that the bias found along the diurnal cycle is linked to a complex three
      factor interaction of bird flight behavior, topography and fix interval. More
      fixes were lost when vultures were perching compared to flying, in rugged versus
      flat topography. But long fix-intervals caused greater loss of fixes in dynamic
      (flying) versus static situations (perching). To conclude, we emphasize the
      importance of evaluating fix-loss bias in current tracking projects, and
      deploying GPS tags that allow remote duty cycle updates so that the most
      appropriate fix and data retrieval intervals can be selected.

PMID- 29020061
TI  - Catching-up: Children with developmental coordination disorder compared to
      healthy children before and after sensorimotor therapy.
AB  - The aims of the present study were to (a) compare healthy children in terms of
      sensorimotor maturity to untreated children diagnosed with developmental
      coordination disorder (DCD) and (b) compare healthy children to diagnosed
      children following completed treatment with sensorimotor therapy. Participants
      were 298 children, 196 boys and 102 girls, distributed into a Norm group of
      healthy children (n = 99) and a group of children diagnosed with DCD (n = 199)
      with a total mean age of 8.77 years (SD = 2.88). Participants in both groups were
      assessed on instruments aimed to detect sensorimotor deviations. The children in
      the DCD group completed, during on average 36 months, sensorimotor therapy which
      comprised stereotypical fetal- and infant movements, vestibular stimulation,
      tactile stimulation, auditory stimulation, complementary play exercises, gross
      motor milestones, and sports-related gross motor skills. At the final visit a
      full assessment was once more performed. Results showed that the Norm group
      performed better on all sensorimotor tests as compared to the untreated children
      from the DCD group, with the exception of an audiometric test where both groups
      performed at the same level. Girls performed better on tests assessing
      proprioceptive and balance abilities. Results also showed, after controls for
      natural maturing effects, that the children from the DCD group after sensorimotor
      therapy did catch up with the healthy children. The concept of "catching-up" is
      used within developmental medicine but has not earlier been documented with
      regard to children and youth in connection with DCD.

PMID- 29020063
TI  - Economic burden of malaria and predictors of cost variability to rural households
      in south-central Ethiopia.
AB  - BACKGROUND: While recognizing the recent remarkable achievement in the global
      malaria reduction, the disease remains a challenge to the malaria endemic
      countries in Africa. Beyond the huge health consequence of malaria, policymakers
      need to be informed about the economic burden of the disease to the households.
      However, evidence on the economic burden of malaria in Ethiopia is scanty. The
      aims of this study were to estimate the economic burden of malaria episode and to
      identify predictors of cost variability to the rural households. METHODS: A
      prospective costing approach from a household perspective was employed. A total
      of 190 malaria patients were enrolled to the study from three health centers and
      nine health posts in Adami Tullu district in south-central Ethiopia, in 2015.
      Primary data were collected on expenditures due to malaria, forgone working days
      because of illness, socioeconomic and demographic situation, and households'
      assets. Quantile regression was applied to predict factors associated with the
      cost variation. Socioeconomic related inequality was measured using concentration
      index and concentration curve. RESULTS: The median cost of malaria per episode to
      the household was USD 5.06 (IQR: 2.98-8.10). The direct cost accounted for 39%,
      while the indirect counterpart accounted for 61%. The history of malaria in the
      last six months and the level of the facility visited in the health system
      predominantly influenced the direct cost. The indirect cost was mainly influenced
      by the availability of antimalarial drugs in the health facility. The
      concentration curve and the concentration index for direct cost indicate
      significant pro-rich inequality. Plasmodium falciparum is significantly more
      costly for households compared to Plasmodium vivax. CONCLUSION: The economic
      burden of malaria to the rural households in Ethiopia was substantial-mainly to
      the poor-indicating that reducing malaria burden could contribute to the poverty
      reduction as well.

PMID- 29020064
TI  - Canine companionship is associated with modification of attentional bias in
      posttraumatic stress disorder.
AB  - Attentional bias towards aversive stimuli has been demonstrated in the anxiety
      disorders and in posttraumatic stress disorder, and attentional bias modification
      has been proposed as a candidate treatment. This study rigorously assessed
      attentional bias towards aversive and pleasant visual imagery associated with the
      presence or absence of a familiar service canine in 23 veterans with chronic
      military-related posttraumatic stress disorder. Participants were repeatedly
      tested with and without their service canines present on two tasks designed to
      elicit spontaneous visual attention to facial and scenic image pairs,
      respectively. Each stimulus contrasted an emotive image with a neutral image. Via
      eye-tracking, the difference in visual attention directed to each image was
      analyzed as a function of the valence contrast and presence/absence of the
      canine. Across both tasks, the presence of a familiar service canine attenuated
      the normative attentional bias towards aversive image content. In the facial
      task, presence of the service canine specifically reduced attention toward angry
      faces. In that task, as well, accumulated days with the service canine similarly
      modulated attention toward facial emotion. The results suggest that the presence
      of a familiar service canine is associated with attenuation of attentional bias
      to aversive stimuli in chronic military-service-related posttraumatic stress
      disorder. Questions remain regarding the generalization of such effects to other
      populations, their dependence on the familiarity, breed, and training of the
      canine, and on social context.

PMID- 29020065
TI  - Gold nanoparticles stabilized with betacyclodextrin-2-amino-4-(4
      chlorophenyl)thiazole complex: A novel system for drug transport.
AB  - While 2-amino-4-(4-chlorophenyl)thiazole (AT) drug and thiazole derivatives have
      several biological applications, these compounds present some drawbacks, such as
      low aqueous solubility and instability. A new complex of betaCD-AT has been
      synthesized to increase AT solubility and has been used as a substrate for the
      deposit of solid-state AuNPs via magnetron sputtering, thus forming the betaCD-AT
      AuNPs ternary system, which is stable in solution. Complex formation has been
      confirmed through powder X-ray diffraction and 1D and 2D nuclear magnetic
      resonance. Importantly, the amine and sulfide groups of AT remained exposed and
      can interact with the surfaces of the AuNPs. The complex association constant
      (970 M-1) has been determined using phase solubility analysis. AuNPs formation
      (32 nm average diameter) has been studied by UV-Visible spectroscopy,
      transmission/scanning electron microscopy and energy-dispersive X-ray analysis.
      The in vitro permeability assays show that effective permeability of AT increased
      using betaCD. In contrast, the ternary system did not have the capacity to
      diffuse through the membrane. Nevertheless, the antibacterial assays have
      demonstrated that AT is transferred from betaCD-AT-AuNPs, being available to
      exert its antibacterial activity. In conclusion, this novel betaCD-AT-AuNPs
      ternary system is a promising alternative to improve the delivery of AT drugs in
      therapy.

PMID- 29020066
TI  - Characteristics of the memory sources of dreams: A new version of the content
      matching paradigm to take mundane and remote memories into account.
AB  - Several studies have demonstrated that dream content is related to the waking
      life of the dreamer. However, the characteristics of the memory sources
      incorporated into dreams are still unclear. We designed a new protocol to
      investigate remote memories and memories of trivial experiences, both relatively
      unexplored in dream content until now. Upon awakening, for 7 days, participants
      identified the waking life elements (WLEs) related to their dream content and
      characterized them and their dream content on several scales to assess notably
      emotional valence. Thanks to this procedure, they could report WLEs from the
      whole lifespan, and mundane ones before they had been forgotten. Participants (N
      = 40, 14 males, age = 25.2 +/- 7.6) reported 6.2 +/- 2.0 dreams on average. For
      each participant, 83.4% +/- 17.8 of the dream reports were related to one or more
      WLEs. Among all the WLEs incorporated into dreams dated by the participants (79.3
      +/- 19%), 40.2 +/- 30% happened the day before the dream, 26.1 +/- 26% the month
      before (the day before excluded), 15.8 +/- 21% the year before the dream (the
      month before excluded), and 17.9 +/- 24% happened more than one year before the
      dream. As could be expected from previous studies, the majority of the WLEs
      incorporated into dreams were scored as important by the dreamers. However, this
      was not true for incorporated WLEs dating from the day before the dream. In
      agreement with Freud's observations, the majority of the day residues were scored
      as mundane. Finally, for both positive and negative WLEs incorporated into
      dreams, the dreamt version of the WLE was rated as emotionally less intense than
      the original WLE. This result, showing that dreams tend to attenuate the
      emotional tone of waking-life memories towards a more neutral one, argues in
      favor of the emotional regulation hypothesis of dreaming.

PMID- 29020067
TI  - Interoception and sexual response in women with low sexual desire.
AB  - Sexual concordance is defined as the association between genital response and
      self-reported sexual arousal. Though one might predict a strong association
      between sexual concordance and awareness of other internal physiological
      sensations (termed interoception), past research on sexually healthy women has
      not found these different domains to be related. The aim of the present study was
      to test the association between interoception and sexual concordance in a
      clinical sample of women with Sexual Interest/Arousal Disorder (SIAD). Fifty-two
      women with SIAD completed the Multidimensional Assessment of Interoceptive
      Awareness (MAIA), a validated self-report measure of interoception, and completed
      a heart-beat accuracy test, an objective measure of interoception. They also
      participated in a laboratory-based assessment of physiological sexual arousal and
      self-reported sexual arousal while viewing an erotic film. Mental and
      physiological arousal were correlated at r = 0.27 (range -0.80 to 0.95). There
      was no significant association between sexual concordance and women's heartrate
      awareness. However, five aspects of interoceptive awareness (noticing, emotional
      awareness, self-regulation, body-listening, and trusting), were predictive of
      lower, and one aspect (not-distracting) was predictive of higher sexual
      concordance. We discuss the findings in relation to the role of emotions and
      arousal states in the interoception-sexual concordance relationship.

PMID- 29020068
TI  - Integrated modeling and analysis of intracellular and intercellular mechanisms in
      shaping the interferon response to viral infection.
AB  - The interferons (IFNs) responses to viral infection are heterogeneous, while the
      underlying mechanisms for variability among cells are still not clear. In this
      study, we developed a hybrid model to systematically identify the sources of IFN
      induction heterogeneity. The experiment-integrated simulation demonstrated that
      the viral dose/type, the diversity in transcriptional factors activation and the
      intercellular paracrine signaling could strikingly shape the heterogeneity of IFN
      expression. We further determined that the IFNbeta and IFNlambda1 induced diverse
      dynamics of IFN-stimulated genes (ISGs) production. Collectively, our findings
      revealed the intracellular and intercellular mechanisms contributing to cell-to
      cell variation in IFN induction, and further demonstrated the significant effects
      of IFN heterogeneity on antagonizing viruses.

PMID- 29020070
TI  - Correction: Mitochondrial Uptake of Thiamin Pyrophosphate: Physiological and Cell
      Biological Aspects.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0073503.].

PMID- 29020069
TI  - Prevalence of risk factors for acquiring measles during the 2011 outbreak in
      Quebec and impact of the province-wide school-based vaccination campaign on
      population immunity.
AB  - BACKGROUND: A large measles outbreak occurred in Quebec, Canada, in 2011.
      Although nearly two-thirds of the cases occurred in only two health districts, a
      mass vaccination campaign targeting all Quebec elementary and high school
      students without valid two-dose history was undertaken to prevent future
      outbreaks. We compared rates of non-vaccination and age at first measles vaccine
      dose among students in the two most-affected districts and the rest of the
      province and estimated the improvement in overall student measles immunity due to
      the mass school-based vaccination campaign. METHODS: Data were extracted from the
      provincial vaccination registry for students in kindergarten to grade 11 during
      the 2011/2012 school year. A telephone survey was conducted in three sub-groups:
      students whose first measles vaccine dose recorded in the vaccination registry
      was received during the 2011 school vaccination campaign; students with no dose
      recorded in the registry whose parents refused receipt during the school
      campaign; and students with no dose recorded in the registry and no information
      about parental consent/refusal during the school campaign. RESULTS: Neither the
      prevalence of being non-vaccinated nor a younger age at first pediatric dose were
      higher in the two most-affected districts versus the rest of the province. The
      school campaign vaccinated nearly 8% of all students including 7% who previously
      received at least one dose. Before the outbreak, 3% of students were not
      vaccinated and one-third of these (1%/3%) were vaccinated during the campaign.
      The campaign likely increased the absolute school population immunity by just
      1.7%. CONCLUSION: The concentration of measles cases in the two most-affected
      health districts during the large Quebec outbreak is not explained by more
      students who were unvaccinated or who had received their first vaccine dose at a
      younger age. The vaccination campaign reached one-third of unvaccinated students
      and only marginally improved population immunity.

PMID- 29020071
TI  - Correction: Pre- and posttreatment with hydrogen sulfide prevents ventilator
      induced lung injury by limiting inflammation and oxidation.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0176649.].

PMID- 29020072
TI  - Correcting for tissue nitrogen excretion in multiple breath washout measurements.
AB  - Nitrogen excreted from body tissues impacts the calculation of multiple breath
      nitrogen washout (MBWN2) outcomes. The aim of this study was to determine the
      effect of tissue N2 on MBWN2 outcomes in both healthy subjects and patients with
      CF and to assess whether it is possible to correct for tissue N2. The
      contribution of tissue N2 to MBWN2 outcomes was estimated by comparing MBWN2
      derived functional residual capacity (FRCN2) to FRC measured by body
      plethysmography (FRCpleth) and by comparing MBW outcome measures derived from
      MBWN2 and sulfur hexafluoride MBW (MBWSF6). Compared to plethysmography and
      MBWSF6, MBWN2 overestimated FRC and lung clearance index (LCI). Application of
      mathematical tissue N2 corrections reduced FRCN2 values closer to FRCpleth in
      health and reduced LCIN2 in both health and CF, but did not explain all of the
      differences observed between N2-dependent and -independent techniques. Use of
      earlier washout cut-offs could reduce the influence of tissue N2. Applying tissue
      N2 corrections to LCIN2 measurements did not significantly affect the
      interpretation of treatment effects reported in a previously published
      interventional trial. While tissue N2 excretion likely has an impact on MBWN2
      outcomes, better understanding of the nature of this phenomenon is required
      before routine correction can be implemented into current MBWN2 protocols.

PMID- 29020073
TI  - Phylloxerids share ancestral carotenoid biosynthesis genes of fungal origin with
      aphids and adelgids.
AB  - Gene transfer among reproductively isolated organisms can lead to novel
      phenotypes and increased fitness. Among the Sternorrhyncha, a suborder of plant
      sap-feeding hemipteran insects, both aphids and adelgids acquired carotenoid
      biosynthesis genes from a fungal donor that result in ecologically relevant
      pigmentation. Phylloxerids form another family that are closely related to aphids
      and adelgids and share similar pigmentation, but are largely uncharacterized for
      their presence and number of pigment genes that have duplicated among aphids.
      Here, we examined the transcriptomes of nine phylloxerid species, and performed
      PCR to amplify carotenoid genes from their genomic DNA. We identified carotenoid
      cyclase/synthase and desaturase genes in each species and demonstrated that they
      share the common fungal origin as those of aphids and adelgids based on their
      exon-intron gene structures and phylogenetic relationships. The phylogenetic
      analyses also indicated that carotenoid genes evolved following the
      differentiation of aphids, adelgids, and phylloxerids at the levels of family,
      genus, and species. Unlike aphids that duplicated these genes in their genomes,
      phylloxerids maintained only single copies, and some species may lack expression
      of certain genes. These results suggest that the phylloxerid lifestyle undergoes
      reduced selection pressure to expand carotenoid synthesis genes, and provides
      insight into these gene functions in insects.

PMID- 29020075
TI  - Correction: Mechanism(S) Involved in the Colon-Specific Expression of the
      Thiamine Pyrophosphate (Tpp) Transporter.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0149255.].

PMID- 29020074
TI  - The ability of algal organic matter and surface runoff to promote the abundance
      of pathogenic and non-pathogenic strains of Vibrio parahaemolyticus in Long
      Island Sound, USA.
AB  - Food safety is a major concern in the shellfish industry, as severe illness can
      result from consuming shellfish that have accumulated waterborne pathogens.
      Shellfish harvesting areas are typically monitored for indicator bacteria such as
      fecal coliforms that serve as proxies for enteric pathogens although these
      indicators have shown little relation to some naturally occurring pathogenic
      bacteria such as Vibrio parahaemolyticus. To examine the dynamics and ecology of
      pathogenic and non-pathogenic strains of V. parahaemolyticus and address the
      relevance of indicator bacteria in predicting V. parahaemolyticus concentrations,
      field surveys and experiments were carried out in western Long Island Sound, NY,
      USA, a region that has experienced recent outbreaks of shellfish contaminated
      with V. parahaemolyticus. Pathogenic and non-pathogenic strains were quantified
      via PCR detection of marker genes and most probable number techniques. Field
      survey data showed little correspondence between fecal coliforms and V.
      parahaemolyticus, but significant correlations between V. parahaemolyticus and an
      alternative indicator, enterococci, and between V. parahaemolyticus and short
      term (48 h) rainfall were observed. Experiments demonstrated that enrichment of
      seawater with phytoplankton-derived dissolved organic matter significantly
      increased the concentration of total V. parahaemolyticus and the presence
      pathogenic V. parahaemolyticus, but higher temperatures did not. Collectively,
      these study results suggest that fecal coliforms may fail to account for the full
      suite of important shellfish pathogens but that enterococci could provide a
      potential alternative or supplement to shellfish sanitation monitoring. Given the
      ability of algal-derived dissolved organic matter to promote the growth of
      pathogenic V. parahaemolyticus, restricting nutrient inputs into coastal water
      bodies that promote algal blooms may indirectly decrease the proliferation of V.
      parahaemolyticus and protect public health.

PMID- 29020077
TI  - Flight aerodynamics in enantiornithines: Information from a new Chinese Early
      Cretaceous bird.
AB  - We describe an exquisitely preserved new avian fossil (BMNHC-PH-919) from the
      Lower Cretaceous Yixian Formation of eastern Inner Mongolia, China. Although
      morphologically similar to Cathayornithidae and other small-sized
      enantiornithines from China's Jehol Biota, many morphological features indicate
      that it represents a new species, here named Junornis houi. The new fossil
      displays most of its plumage including a pair of elongated, rachis-dominated tail
      feathers similarly present in a variety of other enantiornithines. BMNHC-PH-919
      represents the first record of a Jehol enantiornithine from Inner Mongolia, thus
      extending the known distribution of these birds into the eastern portion of this
      region. Furthermore, its well-preserved skeleton and wing outline provide insight
      into the aerodynamic performance of enantiornithines, suggesting that these birds
      had evolved bounding flight-a flight mode common to passeriforms and other small
      living birds-as early as 125 million years ago.

PMID- 29020076
TI  - Recombinant laccase from Pediococcus acidilactici CECT 5930 with ability to
      degrade tyramine.
AB  - Biogenic amines degradation by bacterial laccases is little known, so we have
      cloned and heterologously expressed, in E. coli, a new laccase from Pediococcus
      acidilactici CECT 5930 (Lpa5930), a lactic acid bacterium commonly found in foods
      able to degrade tyramine. The recombinant enzyme has been characterized by
      physical and biochemical assays. Here we report the optimization of expression
      and purification procedures of this laccase. DNA encoding sequence of laccase
      from P. acidilactici was amplified by PCR and cloned into the expression plasmid
      pET28a for induction by isopropyl-beta-D-thiogalactoipyranoside. Protein
      expression was performed in E. coli BL21(DE3) harboring pGro7 plasmid expressing
      a chaperone folding assistant induced by arabinose. Purification was performed by
      column metal-chelating chromatography on Ni-NTA-agarose. The laccase enzyme
      obtained has an apparent molecular mass of ~60 kDa, an optimum temperature
      activity toward 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) of
      28 degrees C, and was quickly inactivated at temperatures higher than 70 degrees
      C. The apparent Km value for ABTS was 1.7 mM and the Vmax obtained was 24 U/mg.
      In addition to ABTS, recombinant Lpa5930 laccase degraded the biogenic amine
      tyramine at pH 9.5 and pH 4.0 with or without ABTS as a mediator. Tyramine
      degradation by laccases could solve the problems generated in food due to the
      presence of this toxic compound.

PMID- 29020078
TI  - Touch-flavor transference: Assessing the effect of packaging weight on gustatory
      evaluations, desire for food and beverages, and willingness to pay.
AB  - Product packaging serves a number of distinct functions and influences the way in
      which consumers respond to various product offerings. The research reported here
      examines whether the haptic characteristics of a non-diagnostic product packaging
      cue, namely its weight, affects the response of consumers. This article reviews
      existing research on haptic transference and proposes a conceptual framework to
      explore how the weight of product packaging affects the flavor of the food or
      beverages, and, in turn, consumers' desire for consumption and willingness to
      pay. Two studies demonstrate that an increase in packaging weight affects both
      desire and willingness to pay for the product. These effects are serially
      mediated by perceived flavor intensity and overall flavor evaluation. Based on
      these insights, implications for the design of food and beverages packaging are
      discussed.

PMID- 29020080
TI  - Correction: Translocation of the neonicotinoid seed treatment clothianidin in
      maize.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0173836.].

PMID- 29020079
TI  - Digitally enhanced recovery: Investigating the use of digital self-tracking for
      monitoring leisure time physical activity of cardiovascular disease (CVD)
      patients undergoing cardiac rehabilitation.
AB  - Research has shown that physical activity is essential in the prevention and
      treatment of chronic diseases like cardiovascular disease (CVD). Smart wearables
      (e.g., smartwatches) are increasingly used to foster and monitor human behaviour,
      including physical activity. However, despite this increased usage, little
      evidence is available on the effects of smart wearables in behaviour change. The
      little research which is available typically focuses on the behaviour of healthy
      individuals rather than patients. In this study, we investigate the effects of
      using smart wearables by patients undergoing cardiac rehabilitation. A field
      experiment involving 29 patients was designed and participants were either
      assigned to the study group (N = 13 patients who finished the study and used a
      self-tracking device) or the control group (N = 16 patients who finished the
      study and did not use a device). For both groups data about physiological
      performance during cardiac stress test was collected at the beginning (baseline),
      in the middle (in week 6, at the end of the rehabilitation in the organized
      rehabilitation setting), and at the end of the study (after 12 weeks, at the end
      of the rehabilitation, including the organized rehabilitation plus another 6
      weeks of self-organized rehabilitation). Comparing the physiological performance
      of both groups, the data showed significant differences. The participants in the
      study group not only maintained the same performance level as during the midterm
      examination in week 6, they improved performance even further during the six
      weeks that followed. The results presented in this paper provide evidence for
      positive effects of digital self-tracking by patients undergoing cardiac
      rehabilitation on performance of the cardiovascular system. In this way, our
      study provides novel insight about the effects of the use of smart wearables by
      CVD patients. Our findings have implications for the design of self-management
      approaches in a patient rehabilitation setting. In essence, the use of smart
      wearables can prolong the success of the rehabilitation outside of the organized
      rehabilitation setting.

PMID- 29020082
TI  - Expression patterns of signaling lymphocytic activation molecule family members
      in peripheral blood mononuclear cell subsets in patients with systemic lupus
      erythematosus.
AB  - Genome-wide linkage analysis studies (GWAS) studies in systemic lupus
      erythematosus (SLE) identified the 1q23 region on human chromosome 1, containing
      the Signaling Lymphocytic Activation Molecule Family (SLAMF) cluster of genes, as
      a lupus susceptibility locus. The SLAMF molecules (SLAMF1-7) are immunoregulatory
      receptors expressed predominantly on hematopoietic cells. Activation of cells of
      the adaptive immune system is aberrant in SLE and dysregulated expression of
      certain SLAMF molecules has been reported. We examined the expression of SLAMF1-7
      on peripheral blood T cells, B cells, monocytes, and their respective
      differentiated subsets, in patients with SLE and healthy controls in a systematic
      manner. SLAMF1 levels were increased on both T cell and B cells and their
      differentiated subpopulations in patients with SLE. SLAMF2 was increased on SLE
      CD4+ and CD8+ T cells. The frequency of SLAMF4+ and SLAMF7+ central memory and
      effector memory CD8+ T cells was reduced in SLE patients. Naive CD4+ and CD8+ SLE
      T cells showed a slight increase in SLAMF3 levels. No differences were seen in
      the expression of SLAMF5 and SLAMF6 among SLE patients and healthy controls.
      Overall, the expression of various SLAMF receptors is dysregulated in SLE and may
      contribute to the immunopathogenesis of the disease.

PMID- 29020081
TI  - Heat stress induces expression of HSP genes in genetically divergent chickens.
AB  - BACKGROUND: Chickens are animals that are sensitive to thermal stress, which may
      decrease their production level in terms that it affects feed intake and thus,
      decreasing body weight gain. The Heat Shock Factors (HSF) and Heat Shock Proteins
      (HSP) genes are involved in the key cellular defense mechanisms during exposure
      in hot environments. Aimed with this study to analyze the expression of HSF1,
      HSF3, HSP70 and HSP90 genes in two local breeds (Peloco and Caneluda) and a
      commercial broiler line (Cobb 500(r)) to verify differences in resistance of
      these chicken to Heat stress treatment. Chicken were submitted to heat stress
      under an average temperature of 39 degrees C +/- 1. RESULTS: Under stress
      environment, the HSP70 and HSP90 genes were more expressed in backyard chickens
      than in broiler. There was a difference in HSP70 and HSP90 expression between
      Caneluda and Cobb and between Peloco and Cobb under stress and comfort
      environment respectively. HSP70 expression is higher in local breeds during heat
      stress than in a commercial broiler line. No significant differences were
      observed in the expression of HSF1 and HSF3 genes between breeds or environments.
      CONCLUSIONS: HSP70 and HSP90 genes are highly expressed, HSF1 and HSF3 genes did
      not have high expression in all genetic groups. HSP70 and HSP90 are highly
      expressed in Peloco and Caneluda within heat stress, these breeds proved to be
      very resistant to high temperature.

PMID- 29020084
TI  - Evaluation of a DNA-based method for spice/herb authentication, so you do not
      have to worry about what is in your curry, buon appetito!
AB  - It is long believed that some spices may help protect against certain chronic
      conditions. Spices are usually parts of plants that have been powdered into small
      pieces. Have you ever wondered what the curry powder in your dish is made of? The
      aim of this work was to develop an appropriate DNA-based method for assessment of
      spice identity. Selecting the best marker for species recognition in the
      Zingiberaceae family. Six DNA regions were investigated in silico, including ITS,
      matK, rbcL, rpoC, trnH-psbA and trnL. Then, only four regions (ITS, matK, rbcL
      and trnH-psbA) were included in the simulated HRM (High-resolution Melting)
      analysis as the results from previous analysis showed that rpoC and trnL may not
      be suitable to be used to identify Zingiberaceae species in HRM analysis based on
      both the percentage of nucleotide variation and GC content. Simulated HRM
      analysis was performed to test the feasibility of Bar-HRM. We found that ITS2 is
      the most effective region to be used for identification of the studied species
      and thus was used in laboratory HRM analysis. All seven tested Zingiberaceae
      plants were then able to be distinguished using the ITS2 primers in laboratory
      HRM. Most importantly the melting curves gained from fresh and dried tissue
      overlapped, which is a crucial outcome for the applicability of the analysis. The
      method could be used in an authentication test for dried products. In the
      authentication test, only one of seven store-sold Zingiberaceae products that
      were tested contained the species listed on their labels, while we found
      substitution/contamination of the tested purchased products in the rest.

PMID- 29020085
TI  - Success rates in smoking cessation: Psychological preparation plays a critical
      role and interacts with other factors such as psychoactive substances.
AB  - INTRODUCTION: The aim of this study was to identify factors associated with the
      results of smoking cessation attempts. METHODS: Data were collected in Clermont
      Ferrand from a smoking cessation clinic between 1999 and 2009 (1,361 patients).
      Smoking cessation was considered a success when patients were abstinent 6 months
      after the beginning of cessation. Multivariate logistic regression was used to
      investigate the association between abstinence and different factors. RESULTS:
      The significant factors were a history of depression (ORadjusted = 0.57, p =
      0.003), state of depression at the initial consultation (ORa = 0.64, p = 0.005),
      other psychoactive substances (ORa = 0.52, p<0.0001), heart, lung and Ear-Nose
      Throat diseases (ORa = 0.65, p = 0.005), age (ORa = 1.04, p<0.0001), the Richmond
      test (p<0.0001; when the patient's motivation went from insufficient to moderate,
      the frequency of abstinence was twice as high) and the Prochaska algorithm
      (p<0.0001; when the patient went from the 'pre-contemplation' to the
      'contemplation' level, the frequency of success was four times higher). A high
      score in the Richmond test had a greater impact on success with increasing age
      (significant interaction: p = 0.01). In exclusive smokers, the contemplation
      level in the Prochaska algorithm was enough to obtain a satisfactory abstinence
      rate (65.5%) whereas among consumers of other psychoactive substances, it was
      necessary to reach the preparation level in the Prochaska algorithm to achieve a
      success rate greater than 50% (significant interaction: p = 0.02). CONCLUSION:
      The psychological preparation of the smoker plays a critical role. The management
      of smoking cessation must be personalized, especially for consumers of other
      psychoactive substances and/or smokers with a history of depression.

PMID- 29020083
TI  - Human macrophages differentiated in the presence of vitamin D3 restrict dengue
      virus infection and innate responses by downregulating mannose receptor
      expression.
AB  - BACKGROUND: Severe dengue disease is associated with high viral loads and
      overproduction of pro-inflammatory cytokines, suggesting impairment in the
      control of dengue virus (DENV) and the mechanisms that regulate cytokine
      production. Vitamin D3 has been described as an important modulator of immune
      responses to several pathogens. Interestingly, increasing evidence has associated
      vitamin D with decreased DENV infection and early disease recovery, yet the
      molecular mechanisms whereby vitamin D reduces DENV infection are not well
      understood. METHODS AND PRINCIPAL FINDINGS: Macrophages represent important cell
      targets for DENV replication and consequently, they are key drivers of dengue
      disease. In this study we evaluated the effect of vitamin D3 on the
      differentiation of monocyte-derived macrophages (MDM) and their susceptibility
      and cytokine response to DENV. Our data demonstrate that MDM differentiated in
      the presence of vitamin D3 (D3-MDM) restrict DENV infection and moderate the
      classical inflammatory cytokine response. Mechanistically, vitamin D3-driven
      differentiation led to reduced surface expression of C-type lectins including the
      mannose receptor (MR, CD206) that is known to act as primary receptor for DENV
      attachment on macrophages and to trigger of immune signaling. Consequently, DENV
      bound less efficiently to vitamin D3-differentiated macrophages, leading to lower
      infection. Interestingly, IL-4 enhanced infection was reduced in D3-MDM by
      restriction of MR expression. Moreover, we detected moderate secretion of TNF
      alpha, IL-1beta, and IL-10 in D3-MDM, likely due to less MR engagement during
      DENV infection. CONCLUSIONS/SIGNIFICANCE: Our findings reveal a molecular
      mechanism by which vitamin D counteracts DENV infection and progression of severe
      disease, and indicates its potential relevance as a preventive or therapeutic
      candidate.

PMID- 29020087
TI  - Residential development alters behavior, movement, and energetics in an apex
      predator, the puma.
AB  - Human development strongly influences large carnivore survival and persistence
      globally. Behavior changes are often the first measureable responses to human
      disturbances, and can have ramifications on animal populations and ecological
      communities. We investigated how a large carnivore responds to anthropogenic
      disturbances by measuring activity, movement behavior, and energetics in pumas
      along a housing density gradient. We used log-linear analyses to examine how
      habitat, time of day, and proximity to housing influenced the activity patterns
      of both male and female pumas in the Santa Cruz Mountains. We used spatial GPS
      location data in combination with Overall Dynamic Body Acceleration measurements
      recorded by onboard accelerometers to quantify how development density affected
      the average distances traveled and energy expended by pumas. Pumas responded to
      development differently depending on the time of day; at night, they were
      generally more active and moved further when they were in developed areas, but
      these relationships were not consistent during the day. Higher nighttime activity
      in developed areas increased daily caloric expenditure by 10.1% for females and
      11.6% for males, resulting in increases of 3.4 and 4.0 deer prey required
      annually by females and males respectively. Our results support that pumas have
      higher energetic costs and resource requirements in human-dominated habitats due
      to human-induced behavioral change. Increased energetic costs for pumas are
      likely to have ramifications on prey species and exacerbate human-wildlife
      conflict, especially as exurban growth continues. Future conservation work should
      consider the consequences of behavioral shifts on animal energetics, individual
      fitness, and population viability.

PMID- 29020086
TI  - Violence, insecurity, and the risk of polio: A systematic analysis.
AB  - BACKGROUND: Since the introduction of polio vaccines in the 1950's and 60's,
      eradication of poliovirus from the world has been technically feasible. Progress
      towards this goal, however, has been uneven and influenced by social and
      political factors that challenge the implementation of robust immunization
      programs. While violence and insecurity are often cited as barriers to
      eradication, current global risk models are largely based on virologic and
      immunologic indicators measured at national levels. In this manuscript, we
      quantify the relevance of indicators of violence and insecurity on the risk of
      polio spread. METHODS AND FINDINGS: Using logistic regression models and public
      data sources, we evaluate the relationship between measures of violence and
      instability and the location of poliomyelitis cases between 2006 and 2015 at the
      country-level, both individually and after controlling for more proximal
      determinants of disease, such as nearby circulating poliovirus and vaccination
      rates. We found that increases in a country's Fragile States Index (FSI) and
      Global Peace Index (GPI), aggregate indicators of violence and instability, were
      associated with the occurrence of poliovirus cases in the subsequent year (p<
      0.01), even after controlling for established risk factors. These effects of
      violence and insecurity must be mediated through immunity and exposure to
      poliovirus, coarse measures of which are included in our model. This also implies
      that in our study, and in risk models in general, the interpretation depends on
      the quality and granularity of available data. CONCLUSION: National virologic and
      immunologic indicators understate the risk of poliovirus spread in areas with
      violence and insecurity, and the inclusion of such factors improves precision. In
      addition, the link between violence and incidence of disease highlights the
      broader challenge of implementing health interventions in conflict areas. We
      discuss practical implications of this work in understanding and measuring the
      risks to polio eradication and other global health initiatives, and the policy
      implications of the need to reach vulnerable populations in conflict zones.

PMID- 29020089
TI  - Correction: Soy and fish as features of the Japanese diet and cardiovascular
      disease risks.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0176039.].

PMID- 29020088
TI  - Expression level of human TLR4 rather than sequence is the key determinant of LPS
      responsiveness.
AB  - To address the role of Toll-like receptor 4 (TLR4) single nucleotide
      polymorphisms (SNP) in lipopolysaccharide (LPS) recognition, we generated mice
      that differed only in the sequence of TLR4. We used a bacterial artificial
      chromosome (BAC) transgenic approach and TLR4/MD-2 knockout mice to specifically
      examine the role of human TLR4 variants in recognition of LPS. Using in vitro and
      in vivo assays we found that the expression level rather than the sequence of
      TLR4 played a larger role in recognition of LPS, especially hypoacylated LPS.

PMID- 29020090
TI  - Saporin-conjugated tetramers identify efficacious anti-HIV CD8+ T-cell
      specificities.
AB  - Antigen-specific T-cells are highly variable, spanning potent antiviral efficacy
      and damaging auto-reactivity. In virus infections, identifying the most
      efficacious responses is critical to vaccine design. However, current methods
      depend on indirect measures or on ex vivo expanded CTL clones. We here describe a
      novel application of cytotoxic saporin-conjugated tetramers to kill antigen
      specific T-cells without significant off-target effects. The relative efficacy of
      distinct antiviral CD8+ T-cell specificity can be directly assessed via antigen
      specific CD8+ T-cell depletion. The utility of these reagents is demonstrated
      here in identifying the CD8+ T-cell specificity most effective in preventing HIV
      progression in HIV-infected HLA-B*27-positive immune controllers.

PMID- 29020092
TI  - Construction of a genetic map using EST-SSR markers and QTL analysis of major
      agronomic characters in hexaploid sweet potato (Ipomoea batatas (L.) Lam).
AB  - The Sweet potato, Ipomoea batatas (L.) Lam, is difficult to study in genetics and
      genomics because it is a hexaploid. The sweet potato study not have been
      performed domestically or internationally. In this study was performed to
      construct genetic map and quantitative trait loci (QTL) analysis. A total of 245
      EST-SSR markers were developed, and the map was constructed by using 210 of those
      markers. The total map length was 1508.1 cM, and the mean distance between
      markers was 7.2 cM. Fifteen characteristics were investigated for QTLs analysis.
      According to those, the Four QTLs were identified, and The LOD score was 3.0.
      Further studies need to develop molecular markers in terms of EST-SSR markers for
      doing to be capable of efficient breeding. The genetic map created here using EST
      SSR markers will facilitate planned breeding of sweet potato cultivars with
      various desirable traits.

PMID- 29020094
TI  - Correction: Expression of MYSM1 is associated with tumor progression in
      colorectal cancer.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0177235.].

PMID- 29020093
TI  - A shift from motorised travel to active transport: What are the potential health
      gains for an Australian city?
AB  - INTRODUCTION: An alarmingly high proportion of the Australian adult population
      does not meet national physical activity guidelines (57%). This is concerning
      because physical inactivity is a risk factor for several chronic diseases. In
      recent years, an increasing emphasis has been placed on the potential for
      transport and urban planning to contribute to increased physical activity via
      greater uptake of active transport (walking, cycling and public transport). In
      this study, we aimed to estimate the potential health gains and savings in health
      care costs of an Australian city achieving its stated travel targets for the use
      of active transport. METHODS: Additional active transport time was estimated for
      the hypothetical scenario of Brisbane (1.1 million population 2013) in Australia
      achieving specified travel targets. A multi-state life table model was used to
      estimate the number of health-adjusted life years, life-years, changes in the
      burden of diseases and injuries, and the health care costs associated with
      changes in physical activity, fine particle (<2.5 MUm; PM2.5) exposure, and road
      trauma attributable to a shift from motorised travel to active transport.
      Sensitivity analyses were conducted to test alternative modelling assumptions.
      RESULTS: Over the life course of the Brisbane adult population in 2013 (860,000
      persons), 33,000 health-adjusted life years could be gained if the travel targets
      were achieved by 2026. This was mainly due to lower risks of physical inactivity
      related diseases, with life course reductions in prevalence and mortality risk in
      the range of 1.5%-6.0%. Prevalence and mortality of respiratory diseases
      increased slightly (>=0.27%) due to increased exposure of larger numbers of
      cyclists and pedestrians to fine particles. The burden of road trauma increased
      by 30% for mortality and 7% for years lived with disability. We calculated
      substantial net savings ($AU183 million, 2013 values) in health care costs.
      CONCLUSION: In cities, such as Brisbane, where over 80% of trips are made by
      private cars, shifts towards walking, cycling and public transport would cause
      substantial net health benefits and savings in health care costs. However, for
      such shifts to occur, investments are needed to ensure safe and convenient
      travel.

PMID- 29020091
TI  - A novel network analysis approach reveals DNA damage, oxidative stress and
      calcium/cAMP homeostasis-associated biomarkers in frontotemporal dementia.
AB  - Frontotemporal Dementia (FTD) is the form of neurodegenerative dementia with the
      highest prevalence after Alzheimer's disease, equally distributed in men and
      women. It includes several variants, generally characterized by behavioural
      instability and language impairments. Although few mendelian genes (MAPT, GRN,
      and C9orf72) have been associated to the FTD phenotype, in most cases there is
      only evidence of multiple risk loci with relatively small effect size. To date,
      there are no comprehensive studies describing FTD at molecular level,
      highlighting possible genetic interactions and signalling pathways at the origin
      FTD-associated neurodegeneration. In this study, we designed a broad FTD genetic
      interaction map of the Italian population, through a novel network-based approach
      modelled on the concepts of disease-relevance and interaction perturbation,
      combining Steiner tree search and Structural Equation Model (SEM) analysis. Our
      results show a strong connection between Calcium/cAMP metabolism, oxidative
      stress-induced Serine/Threonine kinases activation, and postsynaptic membrane
      potentiation, suggesting a possible combination of neuronal damage and loss of
      neuroprotection, leading to cell death. In our model, Calcium/cAMP homeostasis
      and energetic metabolism impairments are primary causes of loss of
      neuroprotection and neural cell damage, respectively. Secondly, the altered
      postsynaptic membrane potentiation, due to the activation of stress-induced
      Serine/Threonine kinases, leads to neurodegeneration. Our study investigates the
      molecular underpinnings of these processes, evidencing key genes and gene
      interactions that may account for a significant fraction of unexplained FTD
      aetiology. We emphasized the key molecular actors in these processes, proposing
      them as novel FTD biomarkers that could be crucial for further epidemiological
      and molecular studies.

PMID- 29020095
TI  - A multiplex PCR mini-barcode assay to identify processed shark products in the
      global trade.
AB  - Protecting sharks from overexploitation has become global priority after
      widespread population declines have occurred. Tracking catches and trade on a
      species-specific basis has proven challenging, in part due to difficulties in
      identifying processed shark products such as fins, meat, and liver oil. This has
      hindered efforts to implement regulations aimed at promoting sustainable use of
      commercially important species and protection of imperiled species. Genetic
      approaches to identify shark products exist but are typically based on sequencing
      or amplifying large DNA regions and may fail to work on heavily processed
      products in which DNA is degraded. Here, we describe a novel multiplex PCR mini
      barcode assay based on two short fragments of the cytochrome oxidase I (COI)
      gene. This assay can identify to species all sharks currently listed on the
      Convention of International Trade of Endangered Species (CITES) and most shark
      species present in the international trade. It achieves species diagnosis based
      on a single PCR and one to two downstream DNA sequencing reactions. The assay is
      capable of identifying highly processed shark products including fins, cooked
      shark fin soup, and skin-care products containing liver oil. This is a
      straightforward and reliable identification method for data collection and
      enforcement of regulations implemented for certain species at all governance
      levels.

PMID- 29020096
TI  - Correction: Aclacinomycin A Sensitizes K562 Chronic Myeloid Leukemia Cells to
      Imatinib through p38MAPK-Mediated Erythroid Differentiation.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0061939.].

PMID- 29020097
TI  - Nuclear and mtDNA phylogenetic analyses clarify the evolutionary history of two
      species of native Hawaiian bats and the taxonomy of Lasiurini (Mammalia:
      Chiroptera).
AB  - Previous studies on genetics of hoary bats produced differing conclusions on the
      timing of their colonization of the Hawaiian Islands and whether or not North
      American (Aeorestes cinereus) and Hawaiian (A. semotus) hoary bats are distinct
      species. One study, using mtDNA COI and nuclear Rag2 and CMA1, concluded that
      hoary bats colonized the Hawaiian Islands no more than 10,000 years ago based on
      indications of population expansion at that time using Extended Bayesian Skyline
      Plots. The other study, using 3 mtDNA and 1 Y-chromosome locus, concluded that
      the Hawaiian Islands were colonized about 1 million years ago. To address the
      marked inconsistencies between those studies, we examined DNA sequences from 4
      mitochondrial and 2 nuclear loci in lasiurine bats to investigate the timing of
      colonization of the Hawaiian Islands by hoary bats, test the hypothesis that
      Hawaiian and North American hoary bats belong to different species, and further
      investigate the generic level taxonomy within the tribe. Phylogenetic analysis
      and dating of the nodes of mtDNA haplotypes and of nuclear CMA1 alleles show that
      A. semotus invaded the Hawaiian Islands approximately 1.35 Ma and that multiple
      arrivals of A. cinereus occurred much more recently. Extended Bayesian Skyline
      plots show population expansion at about 20,000 years ago in the Hawaiian
      Islands, which we conclude does not represent the timing of colonization of the
      Hawaiian Islands given the high degree of genetic differentiation among A.
      cinereus and A. semotus (4.2% divergence at mtDNA Cytb) and the high degree of
      genetic diversity within A. semotus. Rather, population expansion 20,000 years
      ago could have resulted from colonization of additional islands, expansion after
      a bottleneck, or other factors. New genetic data also support the recognition of
      A. semotus and A. cinereus as distinct species, a finding consistent with
      previous morphological and behavioral studies. The phylogenetic analysis of CMA1
      alleles shows the presence of 2 clades that are primarily associated with A.
      semotus mtDNA haplotypes, and are unique to the Hawaiian Islands. There is
      evidence for low levels of hybridization between A. semotus and A. cinereus on
      the Hawaiian Islands, but it is not extensive (<15% of individuals are of hybrid
      origin), and clearly each species is able to maintain its own genetic
      distinctiveness. Both mtDNA and nuclear DNA sequences show deep divergence
      between the 3 groups (genera) of lasiurine bats that correspond to the previously
      recognized morphological differences between them. We show that the Tribe
      Lasiurini contains the genera Aeorestes (hoary bats), Lasiurus (red bats), and
      Dasypterus (yellow bats).

PMID- 29020099
TI  - Experiences of cervical cancer patients in rural Ghana: An exploratory study.
AB  - Even though cervical cancer is quite a prevalent disease in Ghana, there is
      hardly any study on this disease. This paper sought to explore the experiences of
      cervical cancer patients living with the disease with emphasis on their knowledge
      about the disease before and after the diagnosis. Qualitative data were collected
      through in-depth interviews with cervical cancer patients undergoing treatment in
      a specialised cancer treatment health facility in rural Ghana. Cervical cancer
      patients had inadequate knowledge about the disease, its symptoms, risk factors,
      treatment and prevention prior to being diagnosed of the disease. These patients
      were diagnosed late because they usually sought treatment elsewhere before
      reporting to health facilities. They experienced physical, psychological,
      economic and social disruptions in their daily lives, which affected their
      quality of life. It is evident that lack of knowledge about cervical cancer
      constitutes a threat to its prevention and treatment. Intensive health education
      through the mass media and community health promotion outreaches can be a sure
      way of creating adequate knowledge about cervical cancer in Ghana. Treatment and
      care for cervical cancer patients should incorporate counselling sessions, which
      should take into consideration the different levels of disruption the women
      experience and the implications for their wellbeing and management of the
      condition.

PMID- 29020098
TI  - Treatment with high-dose antidepressants severely exacerbates the pathological
      outcome of experimental Escherichia coli infections in poultry.
AB  - There is an urgent need for novel antibiotics as the current antibiotics are
      losing their value due to increased resistance among clinically important
      bacteria. Sertraline, an on-marked anti-depressive drug, has been shown to modify
      bacterial activity in vitro, including increasing the susceptibility of
      Escherichia coli to antibiotics. The aim of the present study was to investigate
      if the antimicrobial activity of sertraline could be documented under clinical
      settings, hereunder if sertraline could potentiate the effect of tetracycline in
      treatment of an experimentally induced ascending infection in poultry. A total of
      40 chickens were divided in four groups of 10 chickens each. All chickens were
      challenged with 4x103 colony forming units (CFU) of a tetracycline resistant E.
      coli strain using a surgical infection model, and subsequently treated with
      either high-dose sertraline, tetracycline, a combination hereof or received no
      treatment. Seven days post challenge all birds were submitted to necropsy and
      scored pathologically for lesions. The average lesion scores were significantly
      higher (P<0.05) in the groups that were treated with high-dose sertraline or high
      dose sertraline combined with tetracycline. In conclusion high-dose treatments
      (four times the maximum therapeutic dose for treating human depression) with
      sertraline as an adjuvant for treatment of antibiotic resistant E. coli
      infections exacerbate the pathological outcome of infection in chickens.

PMID- 29020100
TI  - Biochemical characterization of recombinant influenza A polymerase heterotrimer
      complex: Polymerase activity and mechanisms of action of nucleotide analogs.
AB  - Influenza polymerase is a heterotrimer protein with both endonuclease and RNA
      dependent RNA polymerase (RdRp) activity. It plays a critical role in viral RNA
      replication and transcription and has been targeted for antiviral drug
      development. In this study, we characterized the activity of recombinant RdRp
      purified at 1:1:1 ratio in both ApG-primed RNA replication and mRNA-initiated RNA
      transcription. The heterotrimer complex showed comparable activity profiles to
      that of viral particle derived crude replication complex, and in contrast to the
      crude replication complex, was suitable for detailed mechanistic studies of
      nucleotide incorporation. The recombinant RdRp was further used to examine
      distinct modes of inhibition observed with five different nucleotide analog
      inhibitors, and the apparent steady-state binding affinity Kapp was measured for
      selected analogs to correlate antiviral activity and enzymatic inhibition with
      substrate efficiency.

PMID- 29020101
TI  - Productivity cost due to postpartum ill health: A cross-sectional study in Sri
      Lanka.
AB  - OBJECTIVE: Even though postpartum morbidity continues to cause high disease
      burden in maternal morbidity and mortality across the globe, the literature
      pertaining to resultant productivity loss is scarce. Hence, the present study
      aimed at determining the productivity loss and associated cost of episodes of
      postpartum ill health. METHODS: A cross sectional study was conducted in two
      Medical Officer of Heath areas in the Anuradhapura district, Sri Lanka in 2011,
      among 407 women residing in Anuradhapura district with an infant aged between 8
      to 24 weeks. Validated interviewer administered questionnaires, including the
      IMMPACT productivity cost tool, were used to collect data on self-reported
      episodes of postpartum ill health. The productivity loss was calculated as the
      sum of days lost due to partial and total incapacitation. The adjusted
      productivity loss for coping strategies was calculated. Productivity cost, both
      total and adjusted, were calculated based on the mean daily per capita income of
      the study sample. RESULTS: Of the 407 participants, 161(39.6%) reported at least
      one episode of postpartum illness. Hospitalisations were reported by 27 (16.8%)
      of all symptomatic postpartum women. Common symptoms of postpartum ill health
      were pain/infection at either episiotomy or surgical site (n = 44, 27.3%), lower
      abdominal pain (n = 40, 24.8%) and backache (n = 27, 16.8%). The mean
      productivity loss per episode of ill health was 15 days (SD = 7.8 days) and the
      mean productivity loss per episode after adjusting for coping strategies was 7.9
      days (SD = 4.4 days). The mean productivity cost per an episode was US$
      34.2(95%CI US$ 26.7-41.6) and the mean productivity cost per an episode after
      adjusting for coping strategies was US$ 18.0 (95%CI US$ 14.1-22.0). CONCLUSIONS:
      The prevalence of self-reported postpartum ill health, associated productivity
      loss and cost were high in the study sample and the main contributors were
      preventable conditions including pain and infection. Thus, effective pain
      management and proper infection prevention and control measures are important in
      reducing the burden of postpartum illness and resultant productivity cost.

PMID- 29020103
TI  - Morphometry of the coronary ostia and the structure of coronary arteries in the
      shorthair domestic cat.
AB  - The aim of this study was to measure the area of the coronary ostia, assess their
      localization in the coronary sinuses and to determine the morphology of the stem
      of the left and right coronary arteries in the domestic shorthair cat. The study
      was conducted on 100 hearts of domestic shorthair cats of both sexes, aged 2-18
      years, with an average body weight of 4.05 kg. A morphometric analysis of the
      coronary ostia was carried out on 52 hearts. The remaining 48 hearts were
      injected with a casting material in order to carry out a morphological assessment
      of the left and right coronary arteries. In all the studied animals, the surface
      of the left coronary artery ostium was larger than the surface of the right
      coronary artery ostium. There were four types of the left main coronary artery:
      type I (23 animals, 49%)-double-branched left main stem (giving off the left
      circumflex branch and the interventricular paraconal branch, which in turn gave
      off the septal branch), type II (12 animals, 26%)-double-branched left main stem
      (giving off the left circumflex branch and the interventricular paraconal branch
      without the septal branch), type III (11 animals, 23%)-triple-branched left main
      stem (giving off the left circumflex branch, interventricular branch and the
      septal branch, type IV (1 animal, 2%)-double-branched left main stem (giving off
      the interventricular paraconal branch and the left circumflex branch, which in
      turn gave off the septal branch). The left coronary artery ostium is greater than
      the right one. There is considerable diversity in the branches of proximal
      segment of the left coronary artery, while the right coronary artery is more
      conservative. These results can be useful in defining the optimal strategies in
      the endovascular procedures involving the coronary arteries or the aortic valve
      in the domestic shorthair cat.

PMID- 29020102
TI  - Dusp3 deletion in mice promotes experimental lung tumour metastasis in a
      macrophage dependent manner.
AB  - Vaccinia-H1 Related (VHR) dual-specificity phosphatase, or DUSP3, plays an
      important role in cell cycle regulation and its expression is altered in several
      human cancers. In mouse model, DUSP3 deletion prevents neo-angiogenesis and b-FGF
      induced microvessel outgrowth. Considering the importance of angiogenesis in
      metastasis formation, our study aimed to investigate the role of DUSP3 in tumour
      cell dissemination. Using a Lewis Lung carcinoma (LLC) experimental metastasis
      model, we observed that DUSP3-/- mice developed larger lung metastases than
      littermate controls. DUSP3-/- bone marrow transfer to lethally irradiated
      DUSP3+/+ mice was sufficient to transfer the phenotype to DUSP3+/+ mice,
      indicating that hematopoietic cells compartment was involved in the increased
      tumour cell dissemination to lung tissues. Interestingly, we found a higher
      percentage of tumour-promoting Ly6Cint macrophages in DUSP3-/- LLC-bearing lung
      homogenates that was at least partially due to a better recruitment of these
      cells. This was confirmed by 1) the presence of higher number of the Ly6Bhi
      macrophages in DUSP3-/- lung homogenates and by 2) the better migration of DUSP3
      /- bone marrow sorted monocytes, peritoneal macrophages and bone marrow derived
      macrophages (BMDMs), compared to DUSP3+/+ monocytes, macrophages and BMDMs, in
      response to LLC-conditioned medium. Our study demonstrates that DUSP3 phosphatase
      plays a key role in metastatic growth through a mechanism involving the
      recruitment of macrophages towards LLC-bearing lungs.

PMID- 29020105
TI  - Correction: MPT0B169, a New Antitubulin Agent, Inhibits Bcr-Abl Expression and
      Induces Mitochondrion-Mediated Apoptosis in Nonresistant and Imatinib-Resistant
      Chronic Myeloid Leukemia Cells.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0148093.].

PMID- 29020104
TI  - The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre
      mRNA 3'-end processing.
AB  - Unlike canonical pre-mRNAs, animal replication-dependent histone pre-mRNAs lack
      introns and are processed at the 3'-end by a mechanism distinct from cleavage and
      polyadenylation. They have a 3' stem loop and histone downstream element (HDE)
      that are recognized by stem-loop binding protein (SLBP) and U7 snRNP,
      respectively. The N-terminal domain (NTD) of Lsm11, a component of U7 snRNP,
      interacts with FLASH NTD and these two proteins recruit the histone cleavage
      complex containing the CPSF-73 endonuclease for the cleavage reaction. Here, we
      determined crystal structures of FLASH NTD and found that it forms a coiled-coil
      dimer. Using solution light scattering, we characterized the stoichiometry of the
      FLASH NTD-Lsm11 NTD complex and found that it is a 2:1 heterotrimer, which is
      supported by observations from analytical ultracentrifugation and crosslinking.

PMID- 29020106
TI  - Can Tai Chi training impact fractal stride time dynamics, an index of gait
      health, in older adults? Cross-sectional and randomized trial studies.
AB  - PURPOSE: To determine if Tai Chi (TC) has an impact on long-range correlations
      and fractal-like scaling in gait stride time dynamics, previously shown to be
      associated with aging, neurodegenerative disease, and fall risk. METHODS: Using
      Detrended Fluctuation Analysis (DFA), this study evaluated the impact of TC mind
      body exercise training on stride time dynamics assessed during 10 minute bouts of
      overground walking. A hybrid study design investigated long-term effects of TC
      via a cross-sectional comparison of 27 TC experts (24.5 +/- 11.8 yrs experience)
      and 60 age- and gender matched TC-naive older adults (50-70 yrs). Shorter-term
      effects of TC were assessed by randomly allocating TC-naive participants to
      either 6 months of TC training or to a waitlist control. The alpha (alpha) long
      range scaling coefficient derived from DFA and gait speed were evaluated as
      outcomes. RESULTS: Cross-sectional comparisons using confounder adjusted linear
      models suggest that TC experts exhibited significantly greater long-range scaling
      of gait stride time dynamics compared with TC-naive adults. Longitudinal random
      slopes with shared baseline models accounting for multiple confounders suggest
      that the effects of shorter-term TC training on gait dynamics were not
      statistically significant, but trended in the same direction as longer-term
      effects although effect sizes were very small. In contrast, gait speed was
      unaffected in both cross-sectional and longitudinal comparisons. CONCLUSION:
      These preliminary findings suggest that fractal-like measures of gait health may
      be sufficiently precise to capture the positive effects of exercise in the form
      of Tai Chi, thus warranting further investigation. These results motivate larger
      and longer-duration trials, in both healthy and health-challenged populations, to
      further evaluate the potential of Tai Chi to restore age-related declines in gait
      dynamics. TRIAL REGISTRATION: The randomized trial component of this study was
      registered at ClinicalTrials.gov (NCT01340365).

PMID- 29020108
TI  - Influence of sports flooring and shoes on impact forces and performance during
      jump tasks.
AB  - We aim to determine the influence of sports floorings and sports shoes on impact
      mechanics and performance during standardised jump tasks. Twenty-one male
      volunteers performed ankle jumps (four consecutive maximal bounds with very
      dynamic ankle movements) and multi-jumps (two consecutive maximal counter
      movement jumps) on force plates using minimalist and cushioned shoes under 5
      sports flooring (SF) conditions. The shock absorption properties of the SF,
      defined as the proportion of peak impact force absorbed by the tested flooring
      when compared with a concrete hard surface, were: SF0 = 0% (no flooring), SF1 =
      19%, SF2 = 26%, SF3 = 37% and SF4 = 45%. Shoe and flooring effects were compared
      using 2x5 repeated-measures ANOVA with post-hoc Bonferroni-corrected comparisons.
      A significant interaction between SF and shoe conditions was found for VILR only
      (p = 0.003). In minimalist shoes, SF influenced Vertical Instantaneous Loading
      Rate (VILR) during ankle jumps (p = 0.006) and multi-jumps (p<0.001), in
      accordance with shock absorption properties. However, in cushioned shoes, SF
      influenced VILR during ankle jumps only (p<0.001). Contact Time was the only
      additional variable affected by SF, but only during multi-jumps in minimalist
      shoes (p = 0.037). Cushioned shoes induced lower VILR (p<0.001) and lower Contact
      Time (p<=0.002) during ankle jumps and multi-jumps compared to minimalist shoes.
      During ankle jumps, cushioned shoes induced greater Peak Vertical Ground Reaction
      Force (PVGRF, p = 0.002), greater Vertical Average Loading Rate (p<0.001), and
      lower eccentric (p = 0.008) and concentric (p = 0.004) work. During multi-jumps,
      PVGRF was lower (p<0.001) and jump height was higher (p<0.001) in cushioned
      compared to minimalist shoes. In conclusion, cushioning influenced impact forces
      during standardised jump tasks, whether it was provided by the shoes or the
      sports flooring. VILR is the variable that was the most affected.

PMID- 29020107
TI  - Diacetylenic lipids in the design of stable lipopolymers able to complex and
      protect plasmid DNA.
AB  - Different viral and non-viral vectors have been designed to allow the delivery of
      nucleic acids in gene therapy. In general, non-viral vectors have been associated
      with increased safety for in vivo use; however, issues regarding their efficacy,
      toxicity and stability continue to drive further research. Thus, the aim of this
      study was to evaluate the potential use of the polymerizable diacetylenic lipid
      1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) as a strategy
      to formulate stable cationic lipopolymers in the delivery and protection of
      plasmid DNA. Cationic lipopolymers were prepared following two different
      methodologies by using DC8,9PC, 1,2-dimyristoyl-sn-glycero-3-phosphocholine
      (DMPC), and the cationic lipids (CL) 1,2-dioleoyl-3-trimethylammonium-propane
      (DOTAP), stearylamine (SA), and myristoylcholine chloride (MCL), in a molar ratio
      of 1:1:0.2 (DMPC:DC8,9PC:CL). The copolymerization methodology allowed obtaining
      cationic lipopolymers which were smaller in size than those obtained by the
      cationic addition methodology although both techniques presented high size
      stability over a 166-day incubation period at 4 degrees C. Cationic lipopolymers
      containing DOTAP or MCL were more efficient in complexing DNA than those
      containing SA. Moreover, lipopolymers containing DOTAP were found to form highly
      stable complexes with DNA, able to resist serum DNAses degradation. Furthermore,
      neither of the cationic lipopolymers (with or without DNA) induced red blood cell
      hemolysis, although metabolic activity determined on the L-929 and Vero cell
      lines was found to be dependent on the cell line, the formulation and the
      presence of DNA. The high stability and DNA protection capacity as well as the
      reduced toxicity determined for the cationic lipopolymer containing DOTAP
      highlight the potential advantage of using lipopolymers when designing novel non
      viral carrier systems for use in in vivo gene therapy. Thus, this work represents
      the first steps toward developing a cationic lipopolymer-based gene delivery
      system using polymerizable and cationic lipids.

PMID- 29020110
TI  - Comprehensive benchmarking of SNV callers for highly admixed tumor data.
AB  - Precision medicine attempts to individualize cancer therapy by matching tumor
      specific genetic changes with effective targeted therapies. A crucial first step
      in this process is the reliable identification of cancer-relevant variants, which
      is considerably complicated by the impurity and heterogeneity of clinical tumor
      samples. We compared the impact of admixture of non-cancerous cells and low
      somatic allele frequencies on the sensitivity and precision of 19 state-of-the
      art SNV callers. We studied both whole exome and targeted gene panel data and up
      to 13 distinct parameter configurations for each tool. We found vast differences
      among callers. Based on our comprehensive analyses we recommend joint tumor
      normal calling with MuTect, EBCall or Strelka for whole exome somatic variant
      calling, and HaplotypeCaller or FreeBayes for whole exome germline calling. For
      targeted gene panel data on a single tumor sample, LoFreqStar performed best. We
      further found that tumor impurity and admixture had a negative impact on
      precision, and in particular, sensitivity in whole exome experiments. At
      admixture levels of 60% to 90% sometimes seen in pathological biopsies,
      sensitivity dropped significantly, even when variants were originally present in
      the tumor at 100% allele frequency. Sensitivity to low-frequency SNVs improved
      with targeted panel data, but whole exome data allowed more efficient
      identification of germline variants. Effective somatic variant calling requires
      high-quality pathological samples with minimal admixture, a consciously selected
      sequencing strategy, and the appropriate variant calling tool with settings
      optimized for the chosen type of data.

PMID- 29020111
TI  - Riparian vegetation structure and the hunting behavior of adult estuarine
      crocodiles.
AB  - Riparian ecosystems are amongst the most biodiverse tropical habitats. They are
      important, and essential, ecological corridors, linking remnant forest fragments.
      In this study, we hypothesised that crocodile's actively select nocturnal resting
      locations based on increased macaque predation potential. We examined the
      importance of riparian vegetation structure in the maintenance of crocodile
      hunting behaviours. Using airborne Light Detection and Ranging (LiDAR) and GPS
      telemetry on animal movement, we identified the repeated use of nocturnal resting
      sites by adult estuarine crocodiles (Crocodylus porosus) throughout the
      fragmented Lower Kinabatangan Wildlife Sanctuary in Sabah, Malaysia. Crocodile
      resting locations were found to resemble, in terms of habitat characteristics,
      the sleeping sites of long-tailed macaque; positioned in an attempt to avoid
      predation by terrestrial predators. We found individual crocodiles were actively
      selecting overhanging vegetation and that the protrusion of trees from the tree
      line was key to site selection by crocodiles, as well as influencing both the
      presence and group size of sleeping macaques. Although these findings are
      correlational, they have broad management implications, with the suggestion that
      riparian corridor maintenance and quality can have implications beyond that of
      terrestrial fauna. We further place our findings in the context of the wider
      ecosystem and the maintenance of trophic interactions, and discuss how future
      habitat management has the potential to mitigate human-wildlife conflict.

PMID- 29020109
TI  - Evaluation of repetitive-PCR and matrix-assisted laser desorption ionization-time
      of flight mass spectrometry (MALDI-TOF MS) for rapid strain typing of Bacillus
      coagulans.
AB  - In order to establish rapid and accurate typing method for Bacillus coagulans
      strains which is important for controlling in some canned foods and tea-based
      beverages manufacturing because of the high-heat resistance of the spores and
      high tolerance of the vegetative cells to catechins and chemicals, matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) and repetitive-PCR (rep-PCR) were evaluated. For this purpose, 28 strains of
      B. coagulans obtained from various culture collections were tested. DNA sequence
      analyses of the genes encoding 16S rRNA and DNA gyrase classified the test
      strains into two and three groups, respectively, regardless of their phenotypes.
      Both MALDI-TOF MS and rep-PCR methods classified the test strains in great
      detail. Strains classified in each group showed similar phenotypes, such as
      carbohydrate utilization determined using API 50CH. In particular, the respective
      two pairs of strains which showed the same metabolic characteristic were
      classified into the same group by both MALDI-TOF MS and rep-PCR methods
      separating from the other strains. On the other hand, the other strains which
      have the different profiles of carbohydrate utilization were separated into
      different groups by these methods. These results suggested that the combination
      of MALDI-TOF MS and rep-PCR analyses was advantageous for the rapid and detailed
      typing of bacterial strains in respect to both phenotype and genotype.

PMID- 29020112
TI  - Change of sleep quality from pre- to 3 years post-solid organ transplantation:
      The Swiss Transplant Cohort Study.
AB  - BACKGROUND: Poor sleep quality (SQ) is common after solid organ transplantation;
      however, very little is known about its natural history. We assessed the changes
      in SQ from pre- to 3 years post-transplant in adult heart, kidney, liver and lung
      recipients included in the prospective nation-wide Swiss Transplant Cohort Study.
      We explored associations with selected variables in patients suffering persistent
      poor SQ compared to those with good or variable SQ. METHODS: Adult single organ
      transplant recipients enrolled in the Swiss Transplant Cohort Study with pre
      transplant and at least 3 post-transplant SQ assessment data were included. SQ
      was self-reported pre-transplant (at listing), then at 6, 12, 24 and 36 months
      post-transplant. A single SQ item was used to identify poor (0-5) and good
      sleepers (6-10). Between organ groups, SQ was compared via logistic regression
      analysis with generalized estimating equations. Within the group reporting
      persistently poor SQ, we used logistic regression or Kaplan-Meier analysis as
      appropriate to check for differences in global quality of life and survival.
      RESULTS: In a sample of 1173 transplant patients (age: 52.1+/-13.2 years; 65%
      males; 66% kidney, 17% liver, 10% lung, 7% heart) transplanted between 2008 and
      2012, pre- transplant poor SQ was highest in liver (50%) and heart (49%)
      recipients. Overall, poor SQ decreased significantly from pre-transplant (38%) to
      24 months post-transplant (26%) and remained stable at 3 years (29%). Patients
      reporting persistently poor SQ had significantly more depressive symptomatology
      and lower global quality of life. CONCLUSION: Because self-reported poor SQ is
      related to poorer global quality of life, these results emphasize the need for
      further studies to find suitable treatment options for poor SQ in transplant
      recipients.

PMID- 29020113
TI  - A systematic review of the effectiveness of self-management interventions in
      people with multiple sclerosis at improving depression, anxiety and quality of
      life.
AB  - BACKGROUND: Self-management interventions have become increasingly popular in the
      management of long-term health conditions; however, little is known about their
      impact on psychological well-being in people with Multiple Sclerosis (MS).
      PURPOSE: To examine the effectiveness of self-management interventions on
      improving depression, anxiety and health related quality of life in people with
      MS. METHOD: A structured literature search was conducted for the years 2000 to
      2016. The review process followed the PRISMA guidelines, and is registered with
      PROSPERO (no. CRD42016033925). RESULTS: The review identified 10 RCT trials that
      fulfilled selection criteria and quality appraisal. Self-management interventions
      improved health-related quality of life in 6 out of 7 studies, with some evidence
      of improvement in depression and anxiety symptoms. CONCLUSION: Although the
      results are promising more robust evaluation is required in order to determine
      the effectiveness of self-management interventions on depression, anxiety and
      quality of life in people with MS. Evaluation of the data was impeded by a number
      of methodological issues including incomplete content and delivery information
      for the intervention and the exclusion of participants representing the disease
      spectrum. Recommendations are made for service development and research quality
      improvement.

PMID- 29020114
TI  - How annual course of photoperiod shapes seasonal behavior of diploid and triploid
      oysters, Crassostrea gigas.
AB  - In this work, we study if ploidy (i.e. number of copies of chromosomes) in the
      oyster Crassostrea gigas may introduce differences in behavior and in its
      synchronization by the annual photoperiod. To answer to the question about the
      effect of the seasonal course of the photoperiod on the behavior of C. gigas
      according to its ploidy, we quantified valve activity by HFNI valvometry in situ
      for 1 year in both diploid and triploid oysters. Chronobiological analyses of
      daily, tidal and lunar rhythms were performed according the annual change of the
      photoperiod. In parallel, growth and gametogenesis status were measured and
      spawning events were detected by valvometry. The results showed that triploids
      had reduced gametogenesis, without spawning events, and approximately three times
      more growth than diploids. These differences in physiological efforts could
      explain the result that photoperiod (daylength and/or direction of daylength)
      differentially drives and modulates seasonal behavior of diploid and triploid
      oysters. Most differences were observed during long days (spring and summer),
      where triploids showed longer valve opening duration but lower opening amplitude,
      stronger daily rhythm and weaker tidal rhythm. During this period, diploids did
      major gametogenesis and spawning whereas triploids did maximal growth.
      Differences were also observed in terms of moonlight rhythmicity and neap-spring
      tidal cycle rhythmicity. We suggest that the seasonal change of photoperiod
      differentially synchronizes oyster behavior and biological rhythms according to
      physiological needs based on ploidy.

PMID- 29020115
TI  - Genetic characteristics and molecular epidemiology of vancomycin-resistant
      Enterococci isolates from Caribbean countries.
AB  - Emergence of vancomycin-resistant Enterococci (VRE) that first appeared on the
      stage about three decades ago is now a major concern worldwide as it has globally
      reached every continent. Our aim was to simply undertake a multinational study to
      delineate the resistance and virulence genes of clinical isolates of VRE isolates
      from the Caribbean. We employed both conventional (standard microbiological
      methods including use of E-test strips, chromogenic agar) and molecular methods
      (polymerase chain reactions-PCR, pulsed-field gel electrophoresis-PFGE and
      multilocus sequence typing-MLST) to analyze and characterize 245 Enterococci
      species and 77 VRE isolates from twelve hospitals from eight countries in the
      Caribbean. The PCR confirmed and demonstrated the resistance and virulence genes
      (vanA and esp) among all confirmed VRE isolates. The PFGE delineated clonally
      related isolates from patients from the same country and other countries in the
      region. The main sequence types of the VRE isolates from the region included STs
      412, 750, 203, 736 and 18, all from the common ancestor for clonal complex 17
      (CC17). Despite this common ancestor and association of outbreaks of this lineage
      clones, there has been no reports of outbreaks of infection by VRE in several
      hospitals in the Caribbean.

PMID- 29020116
TI  - Leptin-adiponectin imbalance as a marker of metabolic syndrome among Chinese
      children and adolescents: The BCAMS study.
AB  - PURPOSE: Leptin and adiponectin have opposite effects on subclinical inflammation
      and insulin resistance, both involved in the development of metabolic syndrome
      (MS). We aimed to investigate whether leptin/adiponectin ratio (L/A), as a marker
      of these two adipokines imbalance, may improve diagnosis of MS in children and
      adolescents, and determined its cut-off value in the diagnosis of MS. METHODS: A
      total of 3,428 subjects aged 6-18 years were selected from Beijing Child and
      Adolescent Metabolic Syndrome study. Adipokine leptin and adiponectin were
      measured using enzyme-linked immunosorbent assay. Odds ratio of MS per 1 z-score
      of adipokine was examined using logistic regression. Diagnosis accuracy was
      assessed using c-statistics (AUC) and net reclassification index. RESULTS: The
      levels of leptin and L/A increased with number of positive MS components, while
      the levels of adiponectin declined in both boys and girls (all P <0.001). AUCs
      for diagnosis of MS in girls were 0.793, 0.773, and 0.689 using L/A, leptin and
      adiponectin, respectively; and AUCs in boys were 0.822, 0.798, and 0.697 for L/A,
      leptin and adiponectin, respectively. Notably, L/A outperformed individual leptin
      or adiponectin in discriminating a diagnosis of MS (all P < 0.02 in AUC
      comparisons). In addition, the optimal cut-offs of L/A by ROC curve differed by
      genders and pubertal stages, which were 1.63, 1.28, 1.95 and 1.53 ng/ug for
      total, pre-, mid- and postpubertal boys, respectively and 2.19, 0.87,1.48 and
      2.27 ng/ug for total, pre-, mid- and postpubertal girls, respectively, yielding
      high sensitivity and moderate specificity for a screening test. CONCLUSIONS: In
      this pediatric population, leptin-adiponectin imbalance, as reflected by an
      increase in L/A level, was found to be a better diagnostic biomarker for MS than
      leptin or adiponectin alone. Future longitudinal studies are needed to further
      validate the gender-specific cutoff values.

PMID- 29020117
TI  - A putative Vibrio cholerae two-component system controls a conserved periplasmic
      protein in response to the antimicrobial peptide polymyxin B.
AB  - The epidemic pathogen Vibrio cholerae senses and responds to different external
      stresses it encounters in the aquatic environment and in the human host. One
      stress that V. cholerae encounters in the host is exposure to antimicrobial
      peptides on mucosal surfaces. We used massively parallel cDNA sequencing (RNA
      Seq) to quantitatively identify the transcriptome of V. cholerae grown in the
      presence and absence of sub-lethal concentrations of the antimicrobial peptide
      polymyxin B. We evaluated the transcriptome of both wild type V. cholerae and a
      mutant carrying a deletion of vc1639, a putative sensor kinase of an
      uncharacterized two-component system, under these conditions. In addition to many
      previously uncharacterized pathways responding with elevated transcript levels to
      polymyxin B exposure, we confirmed the predicted elevated transcript levels of a
      previously described LPS modification system in response to polymyxin B exposure.
      Additionally, we identified the V. cholerae homologue of visP (ygiW) as a
      regulatory target of VC1639. VisP is a conserved periplasmic protein implicated
      in lipid A modification in Salmonellae. This study provides the first systematic
      analysis of the transcriptional response of Vibrio cholerae to polymyxin B,
      raising important questions for further study regarding mechanisms used by V.
      cholerae to sense and respond to envelope stress.

PMID- 29020118
TI  - Susceptibility of different mouse strains to oxaliplatin peripheral
      neurotoxicity: Phenotypic and genotypic insights.
AB  - Peripheral neurotoxicity is one of the most distressing side effects of
      oxaliplatin therapy for cancer. Indeed, most patients that received oxaliplatin
      experience acute and/or chronic severe sensory peripheral neuropathy. However,
      despite similar co-morbidities, cancer stage, demographics and treatment
      schedule, patients develop oxaliplatin-induced peripheral neurotoxicity with
      remarkably different severity. This suggests individual genetic variability,
      which might be used to glean the mechanistic insights into oxaliplatin
      neurotoxicity. We characterized the susceptibility of different mice strains to
      oxaliplatin neurotoxicity investigating the phenotypic features of neuropathy and
      gene expression profiles in dorsal root ganglia of six genetically different mice
      strains (Balb-c, C57BL6, DBA/2J, AJ, FVB and CD1) exposed to the same oxaliplatin
      schedule. Differential gene expression in dorsal root ganglia from each mice
      strain were assayed using a genome-wide expression analysis and selected genes
      were validated by RT-PCR analysis. The demonstration of consistent differences in
      the phenotypic response to oxaliplatin across different strains is interesting to
      allow the selection of the appropriate strain based on the pre-defined read-out
      parameters. Further investigation of the correlation between gene expression
      changes and oxaliplatin-induced neurotoxicity phenotype in each strain will be
      useful to deeper investigate the molecular mechanisms of oxaliplatin
      neurotoxicity.

PMID- 29020121
TI  - Food Consumption According to the Days of the Week - National Food Survey, 2008
      2009.
AB  - OBJECTIVE: Evaluate the variations in energy, nutrients, and food groups intake
      between days of the week and weekend days in the Brazilian population. METHODS:
      We used data from the first National Food Survey (2008-2009) of a one-day food
      log of a representative sample of the Brazilian population aged 10 years or older
      (n = 34,003). For the analyses, we considered the sample weights and the effect
      of the study design. The mean (and standard deviations) and frequencies (%) of
      energy, nutrients, and food groups consumption were estimated for weekdays
      (Monday to Friday) and weekend (Saturday and Sunday), we then estimated the
      differences according to the days of the week for the population strata analyzed.
      RESULTS: The average daily energy intake for the weekend was 8% higher than the
      one observed for weekdays. The average percentage contribution of carbohydrate to
      the daily energy intake was higher during the week compared to Saturday and
      Sunday (56.3% versus 54.1%, p < 0.01). The inverse was observed for averages of
      the contribution to the daily intake of energy from total fat (26.8% versus
      28.4%), saturated fat (9.1% versus 9.9%) and trans fat (1.4% versus 1.6%). The
      most significant changes between weekdays and weekend days were observed for
      eggs, sugar-added beverages, puff snacks and chips, beans, and pasta. During
      weekends, the frequency of beverage with added sugar consumption increased by
      34%, the amount consumed increased by 42%, and the contribution to energy intake
      increased by 62% when compared to weekdays. CONCLUSIONS: The Brazilian population
      increases energy intake and unhealthy food markers on weekends compared to
      weekdays.

PMID- 29020122
TI  - Informality and employment vulnerability: application in sellers with subsistence
      work.
AB  - OBJECTIVE: To describe the origin, evolution, and application of the concept of
      employment vulnerability in workers who subsist on street sales. METHODS: We have
      carried out an analysis of the literature in database in Spanish, Portuguese, and
      English, without restriction by country. This is a review of the gray literature
      of government reports, articles, and documents from Latin America and the
      Caribbean. We have analyzed information on the informal economy, social
      employment vulnerability, and subsistence workers. RESULTS AND CONCLUSIONS: The
      concept of informal economy is dispersed and suggested as synonymous with
      employment vulnerability. As a polysemic term, it generates confusion and
      difficulty in identifying defined profiles of employment vulnerability in
      informal subsistence workers, who sell their products on the streets and
      sidewalks of cities. The lack of a clear concept and profile of employment
      vulnerability for this type of workers generates a restriction on defined actions
      to reduce employment vulnerability. The profiles could facilitate access to the
      acquisition of assets that support their structure of opportunities, facilitating
      and mediating in the passage from vulnerability to social mobility with
      opportunities. We propose as a concept of employment vulnerability for
      subsistence workers in the informal sector, the condition of those who must work
      by day to eat at night, who have little or no ownership of assets, and who have a
      minimum structure of opportunities to prevent, face, and resist the critical
      situations that occur daily, putting at risk their subsistence and that of the
      persons who are their responsibility, thus making the connection between social
      and employment vulnerability.

PMID- 29020120
TI  - HPV in women assisted by the Family Health Strategy.
AB  - OBJECTIVE: Estimate the prevalence of cervical HPV infection among women assisted
      by the Family Health Strategy and identify the factors related to the infection.
      METHODS: A cross-sectional study involving 2,076 women aged 20-59 years old
      residing in Juiz de Fora, State of Minas Gerais, who were asked to participate in
      an organized screening carried out in units were the Family Health Strategy had
      been implemented. Participants answered the standardized questionnaire and
      underwent a conventional cervical cytology test and HPV test for high oncogenic
      risk. Estimates of HPV infection prevalence were calculated according to selected
      characteristics referenced in the literature and related to socioeconomic status,
      reproductive health and lifestyle. RESULTS: The overall prevalence of HPV
      infection was 12.6% (95%CI 11.16-14.05). The prevalence for the pooled primer
      contained 12 oncogenic HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and
      68) was 8.6% (95%CI 7.3-9.77). In the multivariate analysis, it was observed that
      the following variables were significantly associated with a higher prevalence of
      HPV infection: marital status (single: adjusted PR = 1.40, 95%CI 1.07-1.8),
      alcohol consumption (any lifetime frequency: adjusted PR = 1.44, 95%CI 1.11-1.86)
      and number of lifetime sexual partners (>= 3: adjusted PR = 1.35, 95%CI 1.04
      1.74). CONCLUSIONS: The prevalence of HPV infection in the study population
      ranges from average to particularly high among young women. The prevalence of
      HPV16 and HPV18 infection is similar to the worldwide prevalence. Homogeneous
      distribution among the pooled primer types would precede the isolated infection
      by HPV18 in magnitude, which may be a difference greater than the one observed.
      The identification of high-risk oncogenic HPV prevalence may help identify women
      at higher risk of developing preneoplastic lesions.

PMID- 29020119
TI  - Human adipose-derived stem cells support the growth of limbal stem/progenitor
      cells.
AB  - The most efficient method to expand limbal stem cells (LSCs) in vitro for
      clinical transplantation is to culture single LSCs directly on growth-arrested
      mouse fibroblast 3T3 cells. To reduce possible xenobiotic contamination from
      3T3s, primary human adipose-derived stem cells (ASCs) were examined as feeder
      cells to support the expansion of LSCs in vitro. To optimize the ASC-supported
      culture, freshly isolated limbal epithelial cells in the form of single cells (SC
      ASC) or cell clusters (CC-ASC) were cultured using three different methods: LSCs
      seeded directly on feeder cells, a 3-dimensional (3D) culture system and a 3D
      culture system with fibrin (fibrin 3D). The expanded LSCs were examined at the
      end of a 2-week culture. The standard 3T3 culture served as control. Expansion of
      SC-ASC showed limited proliferation and exhibited differentiated morphology. CC
      ASC generated epithelial cells with undifferentiated morphology in all culture
      methods, among which CC-ASC in 3D culture supported the highest cell doubling
      (cells doubled 9.0 times compared to cells doubled 4.9 times in control) while
      maintained the percentage of putative limbal stem/progenitor cells compared to
      the control. There were few cell-cell contacts between cultured LSCs and ASCs in
      3D CC-ASC. In conclusion, ASCs support the growth of LSCs in the form of cell
      clusters but not in single cells. 3D CC-ASC could serve as a substitute for the
      standard 3T3 culture to expand LSCs.

PMID- 29020123
TI  - Climatic variability and morbidity and mortality associated with particulate
      matter.
AB  - OBJECTIVE: The objective of this study has been to analyze whether fine
      particulate matter (PM2.5), as well as its synergistic effect with maximum
      temperature, humidity, and seasons, is associated with morbidity and mortality
      from cardiovascular diseases. METHODS: This is an ecological study of time
      series. We have used as outcomes the daily death and hospitalization records of
      adults aged 45 years and over from 2009 to 2011 of the municipalities of Cuiaba
      and Varzea Grande, State of Mato Grosso, Brazil. We have used Poisson regression
      using generalized additive models, assuming a significance level of 5%. The model
      has been controlled for temporal trend, seasonality, average temperature,
      humidity, and season effects. Daily concentrations of PM2.5 (particulate material
      with aerodynamic diameter less than 2.5 micrometers) have been obtained by
      converting the values of optical aerosol thickness. Maximum temperature,
      humidity, and seasons have been separately included in the model as dummy
      variables for the analysis of the synergistic effect of PM2.5 with morbidity and
      mortality from cardiovascular disease. We have calculated the percentage increase
      of relative risk (%RR) of deaths and hospitalizations for the linear increase of
      10 MUg/m3 of PM2.5. RESULTS: Between 2009 and 2011, the increase in PM2.5 was
      associated with a %RR 2.28 (95%CI 0.53-4.06) for hospitalizations on the same day
      of exposure and RR% 3.57 (95%CI 0.82-6.38) for deaths with a lag of three days.
      On hot days, %RR 4.90 (95%CI -0.61-9.38) was observed for deaths. No modification
      of the effect of PM2.5 was observed for maximum temperature in relation to
      hospitalizations. On days with low humidity, %RR was 5.35 (95%CI -0.20-11.22) for
      deaths and 2.71 (95%CI -0.39-5.92) for hospitalizations. In the dry season, %RR
      was 2.35 (95%CI 0.59-4.15) for hospitalizations and 3.43 (95%CI 0.58-6.35) for
      deaths. CONCLUSIONS: The PM2.5 is associated with morbidity and mortality from
      cardiovascular diseases and its effects may be potentiated by heat and low
      humidity and during the dry season.

PMID- 29020125
TI  - Construction and validation of educational materials for the prevention of
      metabolic syndrome in adolescents.
AB  - OBJECTIVE: To develop and validate an educational technology focused on
      prevention of metabolic syndrome among adolescents. METHODS: This was
      methodological research. Using an integrative review, the available publications
      on the subject were analyzed. Then, this knowledge was used to describe the
      theoretical content and, with the help of a graphic designer, the art and layout
      of the pages were developed. In the third phase, the booklet was evaluated and
      validated by 21 specialists and 39 adolescents. Data collection included three
      different questionnaires, according to the focus of evaluation of each group of
      participants, analyzed for reliability (Cronbach's Alpha) and agreement by
      Infraclass Correlation Coefficient. RESULTS: The mean score attributed by
      technical content experts was 91.7%, and the content validity index, measured by
      experts responses, was 0.98, showing high reliability and agreement. In addition,
      the level of agreement of the positive responses given by adolescents was 88.4%.
      CONCLUSION: the educational booklet has proved to be a valid and reliable tool to
      be used for promoting adolescent health.

PMID- 29020124
TI  - Glucose-6-phosphate dehydrogenase deficiency and the use of primaquine: top-down
      and bottom-up estimation of professional costs.
AB  - The aim of this study has been to study whether the top-down method, based on the
      average value identified in the Brazilian Hospitalization System (SIH/SUS), is a
      good estimator of the cost of health professionals per patient, using the bottom
      up method for comparison. The study has been developed from the context of
      hospital care offered to the patient carrier of glucose-6-phosphate dehydrogenase
      (G6PD) deficiency with severe adverse effect because of the use of primaquine, in
      the Brazilian Amazon. The top-down method based on the spending with SIH/SUS
      professional services, as a proxy for this cost, corresponded to R$60.71, and the
      bottom-up, based on the salaries of the physician (R$30.43), nurse (R$16.33), and
      nursing technician (R$5.93), estimated a total cost of R$52.68. The difference
      was only R$8.03, which shows that the amounts paid by the Hospital Inpatient
      Authorization (AIH) are estimates close to those obtained by the bottom-up
      technique for the professionals directly involved in the care.

PMID- 29020126
TI  - Factors associated with acquisition of carbapenem-resistant Enterobacteriaceae.
AB  - OBJECTIVE: to identify possible risk factors for acquisition of Enterobacterial
      strains with a marker for resistance to carbapenems. METHODS: exploratory case
      control study performed in hospital settings. The study sample consisted of
      patients with biological specimens that tested positive for carbapenem-resistant
      Enterobacteriaceae (cases), with the disk diffusion test and Etest, and controls
      with biological samples testing negative for carbapenem-resistant
      Enterobacteriaceae. In all, 65 patients were included: 13 (20%) cases and 52
      (80%) controls. RESULTS: the microorganisms isolated were Serratia marcescens
      (6), Klebsiella pneumoniae (4), and Enterobacter cloacae (3). Univariate analysis
      revealed that length of hospitalization prior to sample collection (p=0.002) and
      having a surgical procedure (p=0.006) were statistically significant. In the
      multivariable logistic regression model, both were still significant, with odds
      ratios of 0.93 (p = 0.009; 95% CI: 0.89 to 0.98) for length of hospitalization
      prior to sample collection, and 9.28 (p = 0.05; 95% CI: 1.01 to 85.14) for having
      a surgical procedure. CONCLUSION: shorter hospitalization times and increased
      surveillance of patients undergoing surgery could play a decisive role in
      reducing the spread of carbapenem-resistant microorganisms in hospital settings.

PMID- 29020127
TI  - An exploration of addiction in adults experiencing early-life stress: a
      metasynthesis.
AB  - OBJECTIVE: to review and synthesize qualitative research on the links between
      early-life stress and addiction behaviours in adulthood. METHOD: metasynthesis to
      review qualitative research findings based on procedures that outline how to
      identify themes or constructs across studies in a specific area. Comprehensive
      searches of multiple electronic databases were performed. The initial search
      yielded 1050 articles and the titles and abstracts were screened for inclusion
      based on predetermined criteria. Thirty-eight full text, peer-reviewed articles
      were retrieved and assessed by three independent reviewers. Twelve articles were
      eligible for full review and appraised using the Critical Appraisal Skills
      Programme (CASP) tools. RESULTS: the findings revealed that clear associations
      exist between early-life stress and addictive behaviours in adulthood, such as
      between trauma in childhood, violence, and addictive behaviours. A common theme
      in the findings indicates that participants turn to addictive substances as a way
      of strategically coping with stressful childhood experiences, regardless of the
      harmful side effects or detrimental social outcomes. CONCLUSION: it can be
      inferred that addiction may be viewed as a way to deal with adversity in
      childhood and that there is an interrelationship between addiction, domestic
      violence and crime.

PMID- 29020128
TI  - Analysis of Longitudinal Studies With Repeated Outcome Measures: Adjusting for
      Time-Dependent Confounding Using Conventional Methods.
AB  - Estimation of causal effects of time-varying exposures using longitudinal data is
      a common problem in epidemiology. When there are time-varying confounders, which
      may include past outcomes, affected by prior exposure, standard regression
      methods can lead to bias. Methods such as inverse probability weighted estimation
      of marginal structural models have been developed to address this problem.
      However, in this paper we show how standard regression methods can be used, even
      in the presence of time-dependent confounding, to estimate the total effect of an
      exposure on a subsequent outcome by controlling appropriately for prior
      exposures, outcomes, and time-varying covariates. We refer to the resulting
      estimation approach as sequential conditional mean models (SCMMs), which can be
      fitted using generalized estimating equations. We outline this approach and
      describe how including propensity score adjustment is advantageous. We compare
      the causal effects being estimated using SCMMs and marginal structural models,
      and we compare the two approaches using simulations. SCMMs enable more precise
      inferences, with greater robustness against model misspecification via propensity
      score adjustment, and easily accommodate continuous exposures and interactions. A
      new test for direct effects of past exposures on a subsequent outcome is
      described.

PMID- 29020129
TI  - Associations Between Maternal Prepregnancy Body Mass Index and Gestational Weight
      Gain and Daughter's Age at Menarche: The Avon Longitudinal Study of Parents and
      Children.
AB  - Earlier puberty and menarche are associated with adverse health outcomes.
      Reported associations of maternal adiposity with daughter's age at menarche are
      inconsistent. We examined associations between maternal prepregnancy body mass
      index (BMI; weight (kg)/height (m)2) and gestational weight gain (GWG) and
      daughter's ages at menarche (n = 3,935 mother-offspring pairs), pubarche (Tanner
      stage 2 for pubic hair) (n = 2,942 pairs), and thelarche (Tanner stage 2 for
      breast development) (n = 2,942 pairs) in the Avon Longitudinal Study of Parents
      and Children, a prospective United Kingdom pregnancy cohort study (baseline 1991
      1992). During a follow-up period of up to 17 years (1991-2008), mean menarcheal
      age was 12.6 (standard deviation, 1.2) years. Both maternal prepregnancy BMI and
      GWG were inversely associated with daughter's age at menarche after adjustment
      for maternal age, parity, socioeconomic status, smoking, maternal menarcheal age,
      and ethnicity (mean differences were -0.34 months (95% confidence interval: 
      0.45, -0.22) per BMI unit and -0.17 months (95% confidence interval: -0.26, 
      0.07) per kg, respectively). Associations remained unchanged after adjustment for
      birth weight and gestational age but were attenuated to the null when results
      were adjusted for daughter's prepubertal BMI. Similar results were found for ages
      at pubarche and thelarche. These findings indicate that greater prepregnancy BMI
      and GWG are associated with earlier puberty in daughters and that these
      associations are mediated by daughters' prepubertal BMIs.

PMID- 29020130
TI  - Partial Mediation by Cadmium Exposure of the Association Between Tobacco Smoking
      and Atherosclerotic Plaques in the Carotid Artery.
AB  - Exposure to cadmium confers increased cardiovascular risk. Tobacco smoke contains
      cadmium, which, hypothetically, may mediate parts of the tobacco-associated risk
      of developing atherosclerotic plaques. Baseline data from the Swedish Malmo Diet
      and Cancer cohort (1991-1996) were used to test this hypothesis. Mediation
      analysis was used to examine associations between smoking and blood cadmium
      levels and the prevalence of ultrasound-assessed carotid atherosclerotic plaques.
      The total association with smoking status (never smokers, 2 categories of former
      smokers, and current smokers) was split into direct and indirect association, and
      the proportion mediated was estimated. The adjusted estimated plaque prevalence
      was approximately 27% among never smokers. We identified both a direct and an
      indirect pathway between smoking and carotid plaques; the indirect association,
      through cadmium, was observed among current smokers and former smokers who had
      quit smoking less than 15 years before. For current smokers, the prevalence ratio
      for plaque was 1.5, with 60%-65% of the association with smoking being mediated
      through cadmium. Recent former smokers had a prevalence ratio of 1.3, and 40%-45%
      was mediated through cadmium. Long-time former smokers had a prevalence ratio of
      1.2, but none of the association was mediated through cadmium. In conclusion,
      about two-thirds of the proatherosclerotic association with smoking was mediated
      by cadmium.

PMID- 29020131
TI  - Data-Adaptive Estimation for Double-Robust Methods in Population-Based Cancer
      Epidemiology: Risk Differences for Lung Cancer Mortality by Emergency
      Presentation.
AB  - In this paper, we propose a structural framework for population-based cancer
      epidemiology and evaluate the performance of double-robust estimators for a
      binary exposure in cancer mortality. We conduct numerical analyses to study the
      bias and efficiency of these estimators. Furthermore, we compare 2 different
      model selection strategies based on 1) Akaike's Information Criterion and the
      Bayesian Information Criterion and 2) machine learning algorithms, and we
      illustrate double-robust estimators' performance in a real-world setting. In
      simulations with correctly specified models and near-positivity violations, all
      but the naive estimators had relatively good performance. However, the augmented
      inverse-probability-of-treatment weighting estimator showed the largest relative
      bias. Under dual model misspecification and near-positivity violations, all
      double-robust estimators were biased. Nevertheless, the targeted maximum
      likelihood estimator showed the best bias-variance trade-off, more precise
      estimates, and appropriate 95% confidence interval coverage, supporting the use
      of the data-adaptive model selection strategies based on machine learning
      algorithms. We applied these methods to estimate adjusted 1-year mortality risk
      differences in 183,426 lung cancer patients diagnosed after admittance to an
      emergency department versus persons with a nonemergency cancer diagnosis in
      England (2006-2013). The adjusted mortality risk (for patients diagnosed with
      lung cancer after admittance to an emergency department) was 16% higher in men
      and 18% higher in women, suggesting the importance of interventions targeting
      early detection of lung cancer signs and symptoms.

PMID- 29020132
TI  - The Relationship Between Occupational Standing and Sitting and Incident Heart
      Disease Over a 12-Year Period in Ontario, Canada.
AB  - While a growing body of research is examining the impacts of prolonged
      occupational sitting on cardiovascular and other health risk factors, relatively
      little work has examined the effects of occupational standing. The objectives of
      this paper were to examine the relationship between occupations that require
      predominantly sitting and those that require predominantly standing and incident
      heart disease. A prospective cohort study combining responses to a population
      health survey with administrative health-care records, linked at the individual
      level, was conducted in Ontario, Canada. The sample included 7,320 employed labor
      market participants (50% male) working 15 hours a week or more and free of heart
      disease at baseline. Incident heart disease was assessed using administrative
      records over an approximately 12-year follow-up period (2003-2015). Models
      adjusted for a wide range of potential confounding factors. Occupations involving
      predominantly standing were associated with an approximately 2-fold risk of heart
      disease compared with occupations involving predominantly sitting. This
      association was robust to adjustment for other health, sociodemographic, and work
      variables. Cardiovascular risk associated with occupations that involve
      combinations of sitting, standing, and walking differed for men and women, with
      these occupations associated with lower cardiovascular risk estimates among men
      but elevated risk estimates among women.

PMID- 29020134
TI  - Occurrence of Selected Structural Birth Defects Among Women With Preeclampsia and
      Other Hypertensive Disorders.
AB  - To explore a potential association between preeclampsia and selected birth
      defects, we examined the prevalence of certain birth defects among women with
      hypertensive disorders including preeclampsia. We analyzed data from 2,499,536
      singleton live births in California from 2007 to 2011, including maternal and
      infant demographics from birth certificates as well as clinical details from
      delivery hospitalization records. We examined defect groups that were
      recognizable at birth (e.g., spina bifida and cleft lip). Hypertensive disorders
      included preexisting hypertension, gestational hypertension, mild preeclampsia,
      severe preeclampsia/eclampsia, and preeclampsia superimposed on preexisting
      hypertension. Relative risk values with 95% confidence intervals for each birth
      defect were calculated by hypertensive group, as well as independent and joint
      associations of hypertensive and diabetic disorders. Risks of each type of birth
      defect were higher among offspring of women with hypertensive disorders compared
      with those without. The risks of birth defects among offspring of women with only
      a hypertensive disorder were significantly higher than that among women with
      neither hypertensive nor diabetic disorders (relative risks ranged from 1.37 to
      2.77). Risks of birth defects were highest among those born to women with both
      hypertensive and diabetic disorders compared with those with neither (relative
      risks ranged from 1.80 to 6.22). These findings support the existence of an
      association between preeclampsia and certain birth defects and suggest that
      diabetes may be a contributing factor.

PMID- 29020135
TI  - Separation in Logistic Regression: Causes, Consequences, and Control.
AB  - Separation is encountered in regression models with a discrete outcome (such as
      logistic regression) where the covariates perfectly predict the outcome. It is
      most frequent under the same conditions that lead to small-sample and sparse-data
      bias, such as presence of a rare outcome, rare exposures, highly correlated
      covariates, or covariates with strong effects. In theory, separation will produce
      infinite estimates for some coefficients. In practice, however, separation may be
      unnoticed or mishandled because of software limits in recognizing and handling
      the problem and in notifying the user. We discuss causes of separation in
      logistic regression and describe how common software packages deal with it. We
      then describe methods that remove separation, focusing on the same penalized
      likelihood techniques used to address more general sparse-data problems. These
      methods improve accuracy, avoid software problems, and allow interpretation as
      Bayesian analyses with weakly informative priors. We discuss likelihood
      penalties, including some that can be implemented easily with any software
      package, and their relative advantages and disadvantages. We provide an
      illustration of ideas and methods using data from a case-control study of
      contraceptive practices and urinary tract infection.

PMID- 29020136
TI  - Traffic-Related Air Pollution and Autism Spectrum Disorder: A Population-Based
      Nested Case-Control Study in Israel.
AB  - Accumulating evidence suggests that perinatal air pollutant exposures are
      associated with increased risk of autism spectrum disorder (ASD), but evidence
      for traffic pollutants outside the United States is inconclusive. We assessed the
      association between nitrogen dioxide, a traffic pollution tracer, and risk of
      ASD. We conducted a nested case-control study among the entire population of
      children born during 2005-2009 in the central coastal area of Israel. Cases were
      identified through the National Insurance Institute of Israel (n = 2,098).
      Controls were a 20% random sample of the remaining children (n = 54,191).
      Exposure was based on an optimized dispersion model. We estimated adjusted odds
      ratios and 95% confidence intervals using logistic regression and a distributed
      lag model. In models mutually adjusted for the 2 periods, the odds ratio per 5.85
      parts per billion (ppb) increment of nitrogen dioxide exposure during pregnancy
      (median, 16.8 ppb; range, 7.5-31.2 ppb) was 0.77 (95% confidence interval: 0.59,
      1.00), and the odds ratio for exposure during the 9 months after birth was 1.40
      (95% confidence interval: 1.09, 1.80). A distributed-lag model revealed reduced
      risk around week 13 of pregnancy and elevated risk around week 26 after birth.
      These findings suggest that postnatal exposure to nitrogen dioxide in Israel is
      associated with increased odds of ASD, and prenatal exposure with lower odds. The
      latter may relate to selection effects.

PMID- 29020133
TI  - Blood Lead, Bone Turnover, and Survival in Amyotrophic Lateral Sclerosis.
AB  - Blood lead and bone turnover may be associated with the risk of amyotrophic
      lateral sclerosis (ALS). We aimed to assess whether these factors were also
      associated with time from ALS diagnosis to death through a survival analysis of
      145 ALS patients enrolled during 2007 in the National Registry of Veterans with
      ALS. Associations of survival time with blood lead and plasma biomarkers of bone
      resorption (C-terminal telopeptides of type I collagen (CTX)) and bone formation
      (procollagen type I amino-terminal peptide (PINP)) were estimated using Cox
      models adjusted for age at diagnosis, diagnostic certainty, diagnostic delay,
      site of onset, and score on the Revised ALS Functional Rating Scale. Hazard
      ratios were calculated for each doubling of biomarker concentration. Blood lead,
      plasma CTX, and plasma PINP were mutually adjusted for one another. Increased
      lead (hazard ratio (HR) = 1.38; 95% confidence interval (CI): 1.03, 1.84) and CTX
      (HR = 2.03; 95% CI: 1.42, 2.89) were both associated with shorter survival,
      whereas higher PINP was associated with longer survival (HR = 0.59; 95% CI: 0.42,
      0.83), after ALS diagnosis. No interactions were observed between lead or bone
      turnover and other prognostic indicators. Lead toxicity and bone metabolism may
      be involved in ALS pathophysiology.

PMID- 29020137
TI  - Associations of Residential Socioeconomic, Food, and Built Environments With
      Glycemic Control in Persons With Diabetes in New York City From 2007-2013.
AB  - In the present study, we examined the longitudinal associations between
      residential environmental factors and glycemic control in 182,756 adults with
      diabetes in New York City from 2007 to 2013. Glycemic control was defined as a
      hemoglobin A1c (HbA1c) level less than 7%. We constructed residential-level
      measures and performed principle component analysis to formulate a residential
      composite score. On the basis of this score, we divided residential areas into
      quintiles, with the lowest and highest quintiles reflecting the least and most
      advantaged residential environments, respectively. Several residential-level
      environmental characteristics, including more advantaged socioeconomic
      conditions, greater ratio of healthy food outlets to unhealthy food outlets, and
      residential walkability were associated with increased glycemic control.
      Individuals who lived continuously in the most advantaged residential areas took
      less time to achieve glycemic control compared with the individuals who lived
      continuously in the least advantaged residential areas (9.9 vs. 11.5 months).
      Moving from less advantaged residential areas to more advantaged residential
      areas was related to improved diabetes control (decrease in HbA1c = 0.40%, 95%
      confidence interval: 0.22, 0.55), whereas moving from more advantaged residential
      areas to less advantaged residential areas was related to worsening diabetes
      control (increase in HbA1c = 0.33%, 95% confidence interval: 0.24, 0.44). These
      results show that residential areas with greater resources to support healthy
      food and residential walkability are associated with improved glycemic control in
      persons with diabetes.

PMID- 29020138
TI  - Understanding Causal Distributional and Subgroup Effects With the Instrumental
      Propensity Score.
AB  - To address issues with measured and unmeasured confounding in observational
      studies, we developed a unified approach to using an instrumental variable in
      more flexible ways to evaluate treatment effects. The approach is based on an
      instrumental propensity score conditional on baseline variables, which can then
      be incorporated in matching, regression, subclassification, or weighting along
      with various parametric, semiparametric, or nonparametric methods for the
      assessment of treatment effects. Therefore, the application of the instrumental
      propensity score allows different methods for outcome effect evaluations in
      addition to standard 2-stage least square models while controlling for unmeasured
      confounders. Several properties of the instrumental propensity score are
      discussed. The approach is then illustrated using subclassification along with a
      semiparametric density ratio model and empirical likelihood. This method allows
      us to evaluate distributional and subgroup treatment effects in addition to the
      overall average treatment effect. Simulation studies showed that the method works
      well. We applied our method to a study of the effects of attending a Catholic
      school versus a public school and found that attending a Catholic school had
      significant beneficial effects on subsequent wages among a subgroup of subjects.

PMID- 29020139
TI  - Coffee Intake and Incidence of Erectile Dysfunction.
AB  - Coffee intake is suggested to have a positive impact on chronic diseases, yet its
      role in urological diseases such as erectile dysfunction (ED) remains unclear. We
      investigated the association of coffee intake with incidence of ED by conducting
      the Health Professionals Follow-Up Study, a prospective analysis of 21,403 men
      aged 40-75 years old. Total, regular, and decaffeinated coffee intakes were self
      reported on food frequency questionnaires. ED was assessed by mean values of
      questionnaires in 2000, 2004 and 2008. Multivariable adjusted Cox proportional
      hazards models were used to compute hazard ratios for patients with incident ED
      (n = 7,298). No significant differences were identified for patients with
      incident ED after comparing highest (>=4 cups/day) with lowest (0 cups/day)
      categories of total (hazard ratio (HR) = 1.00, 95% confidence interval (CI):
      0.90, 1.11) and regular coffee intakes (HR = 1.00, 95% CI: 0.89, 1.13). When
      comparing the highest category with lowest category of decaffeinated coffee
      intake, we found a 37% increased risk of ED (HR = 1.37, 95% CI: 1.08, 1.73), with
      a significant trend (P trend = 0.02). Stratified analyses also showed an
      association among current smokers (P trend = 0.005). Overall, long-term coffee
      intake was not associated with risk of ED in a prospective cohort study.

PMID- 29020140
TI  - Characteristics of Social Networks and Mortality Risk: Evidence From 2
      Prospective Cohort Studies.
AB  - The size of a person's social network is linked to health and longevity, but it
      is unclear whether the number of strong social ties or the number of weak social
      ties is most influential for health. We examined social network characteristics
      as predictors of mortality in the Finnish Public Sector Study (n = 7,617) and the
      Health and Social Support Study (n = 20,816). Social network characteristics were
      surveyed at baseline in 1998. Information about mortality was obtained from the
      Finnish National Death Registry. During a mean follow-up period of 16 years,
      participants with a small social network (<=10 members) were more likely to die
      than those with a large social network (>=21 members) (adjusted hazard ratio (HR)
      = 1.23, 95% confidence interval (CI): 1.04, 1.46). Mortality risk was increased
      among participants with both a small number of strong ties (<=2 members) and a
      small number of weak ties (<=5 members) (HR = 1.55, 95% CI: 1.26, 1.79) and among
      participants with both a large number of strong ties and a small number of weak
      ties (HR = 1.28, 95% CI: 1.08, 1.52), but not among those with a small number of
      strong ties and a large number of weak ties (HR = 1.04, 95% CI: 0.87, 1.25).
      These findings suggest that in terms of mortality risk, the number of weak ties
      may be an important component of social networks.

PMID- 29020141
TI  - Best Practices for Gauging Evidence of Causality in Air Pollution Epidemiology.
AB  - The contentious political climate surrounding air pollution regulations has
      brought some researchers and policy-makers to argue that evidence of causality is
      necessary before implementing more stringent regulations. Recently, investigators
      in an increasing number of air pollution studies have purported to have used
      "causal analysis," generating the impression that studies not explicitly labeled
      as such are merely "associational" and therefore less rigorous. Using 3 prominent
      air pollution studies as examples, we review good practices for how to critically
      evaluate the extent to which an air pollution study provides evidence of
      causality. We argue that evidence of causality should be gauged by a critical
      evaluation of design decisions such as 1) what actions or exposure levels are
      being compared, 2) whether an adequate comparison group was constructed, and 3)
      how closely these design decisions approximate an idealized randomized study. We
      argue that air pollution studies that are more scientifically rigorous in terms
      of the decisions made to approximate a randomized experiment are more likely to
      provide evidence of causality and should be prioritized among the body of
      evidence for regulatory review accordingly. Our considerations, although
      presented in the context of air pollution epidemiology, can be broadly applied to
      other fields of epidemiology.

PMID- 29020143
TI  - Anti-infective Acquisition Costs for a Stewardship Program: Getting to the Bottom
      Line.
AB  - Background: Though antimicrobial stewardship programs (ASPs) are in place for
      patient safety, financial justification is often required. In 2016, the
      Infectious Diseases Society of America (IDSA) recommended that anti-infective
      costs be measured by patient-level administration data normalized for patient
      census. Few publications use this methodology. Here, we aim to compare 3 methods
      of drug cost analysis during 3 phases of an ASP as an example of this
      recommendation's implementation. Methods: At a freestanding pediatric hospital,
      we retrospectively assessed anti-infective cost using pharmacy purchasing data,
      patient-level administration data from the electronic medical record (EMR), and
      patient-level administration data from the Pediatric Hospital Information Systems
      (PHIS) database, all normalized to patient census. Costs pre-ASP, while planning
      the ASP, and post-ASP were then compared for each method. Results: Significant
      differences in costs between the methods were observed. Pharmacy purchasing
      endorsed minimal financial benefit (decrease planning to post-ASP of $590 dollars
      per 1000 patient-days), while the EMR and PHIS data endorsed a decrease of $12785
      and $21380 per 1000 patient-days, respectively, for a total yearly cost savings
      of $54656 for pharmacy purchasing data, $1184336 for EMR data, and $2117522 for
      PHIS data. Conclusions: Pharmacy purchasing data underestimated cost savings
      compared with EMR and PHIS data, while EMR and PHIS data were comparable in
      magnitude of savings. At Children's Hospital Colorado, savings justified the full
      cost of the ASP. EMR patient-level administration data, normalized to patient
      census, offers a readily available and standardized measure of anti-infective
      costs over time.

PMID- 29020142
TI  - Possible Mediation by Methylation in Acute Inflammation Following Personal
      Exposure to Fine Particulate Air Pollution.
AB  - Air pollution may increase cardiovascular and respiratory risk through
      inflammatory pathways, but evidence for acute effects has been weak and indirect.
      Between December 2014 and July 2015, we enrolled 36 healthy, nonsmoking college
      students for a panel study in Shanghai, China, a city with highly variable levels
      of air pollution. We measured personal exposure to particulate matter with an
      aerodynamic diameter less than or equal to 2.5 MUm (PM2.5) continuously for 72
      hours preceding each of 4 clinical visits that included phlebotomy. We measured 4
      inflammation proteins and DNA methylation at nearby regulatory cytosine-phosphate
      guanine (CpG) loci. We applied linear mixed-effect models to examine associations
      over various lag times. When results suggested mediation, we evaluated
      methylation as mediator. Increased PM2.5 concentration was positively associated
      with all 4 inflammation proteins and negatively associated with DNA methylation
      at regulatory loci for tumor necrosis factor alpha (TNF-alpha) and soluble
      intercellular adhesion molecule-1. A 10-MUg/m3 increase in average PM2.5 during
      the 24 hours preceding blood draw corresponded to a 4.4% increase in TNF-alpha
      and a statistically significant decrease in methylation at one of the two studied
      candidate CpG loci for TNF-alpha. Epigenetics may play an important role in
      mediating effects of PM2.5 on inflammatory pathways.

PMID- 29020144
TI  - Increasing Campylobacter Infections, Outbreaks, and Antimicrobial Resistance in
      the United States, 2004-2012.
AB  - Background: Campylobacteriosis, a leading cause of foodborne illness in the
      United States, was not nationally notifiable until 2015. Data describing national
      patterns and trends are limited. We describe the epidemiology of Campylobacter
      infections in the United States during 2004-2012. Methods: We summarized
      laboratory-confirmed campylobacteriosis data from the Nationally Notifiable
      Disease Surveillance System, National Outbreak Reporting System, National
      Antimicrobial Resistance Monitoring System, and Foodborne Diseases Active
      Surveillance Network. Results: During 2004-2012, 303520 culture-confirmed
      campylobacteriosis cases were reported. Average annual incidence rate (IR) was
      11.4 cases/100000 persons, with substantial variation by state (range, 3.1-47.6
      cases/100000 persons). IRs among patients aged 0-4 years were more than double
      overall IRs. IRs were highest among males in all age groups. IRs in western
      states and rural counties were higher (16.2/100000 and 14.2/100000, respectively)
      than southern states and metropolitan counties (6.8/100000 and 11.0/100000,
      respectively). Annual IRs increased 21% from 10.5/100000 during 2004-2006 to
      12.7/100000 during 2010-2012, with the greatest increases among persons aged >60
      years (40%) and in southern states (32%). The annual median number of
      Campylobacter outbreaks increased from 28 in 2004-2006 to 56 in 2010-2012; in
      total, 347 were reported. Antimicrobial susceptibility testing of isolates from
      4793 domestic and 1070 travel-associated infections revealed that, comparing 2004
      2009 to 2010-2012, ciprofloxacin resistance increased among domestic infections
      (12.8% vs 16.1%). Conclusions: During 2004-2012, incidence of campylobacteriosis,
      outbreaks, and clinically significant antimicrobial resistance increased. Marked
      demographic and geographic differences exist. Our findings underscore the
      importance of national surveillance and understanding of risk factors to guide
      and target control measures.

PMID- 29020145
TI  - Interferon-gamma-Inducible Protein 10 (IP-10) as a Screening Tool to Optimize
      Human Immunodeficiency Virus RNA Monitoring in Resource-Limited Settings.
AB  - Background: Achieving effective antiretroviral treatment (ART) monitoring is a
      key determinant to ensure viral suppression and reach the UNAIDS 90-90-90
      targets. The gold standard for detecting virological failure is plasma human
      immunodeficiency virus (HIV) RNA (viral load [VL]) testing; however, its
      availability is very limited in low-income countries due to cost and operational
      constraints. Methods: HIV-1-infected adults on first-line ART attending routine
      visits at the Manhica District Hospital, Mozambique, were previously evaluated
      for virologic failure. Plasma levels of interferon-gamma-inducible protein 10 (IP
      10) were quantified by enzyme-linked immunosorbent assay. Logistic regression was
      used to build an IP-10-based model able to identify individuals with VL >150
      copies/mL. From the 316 individuals analyzed, 253 (80%) were used for model
      training and 63 (20%) for validation. Receiver operating characteristic curves
      were employed to evaluate model prediction. Results: From the individuals
      included in the training set, 34% had detectable VL. Mean age was 41 years, 70%
      were females, and median time on ART was 3.4 years. IP-10 levels were
      significantly higher in subjects with detectable VL (108.2 pg/mL) as compared to
      those with undetectable VL (38.0 pg/mL) (P < .0001, U test). IP-10 univariate
      model demonstrated high classification performance (area under the curve = 0.85
      [95% confidence interval {CI}, .80-.90]). Using a cutoff value of IP-10 >=44.2
      pg/mL, the model identified detectable VL with 91.9% sensitivity (95% CI, 83.9%
      96.7%) and 59.9% specificity (95% CI, 52.0%-67.4%), values confirmed in the
      validation set. Conclusions: IP-10 is an accurate biomarker to screen individuals
      on ART for detectable viremia. Further studies should evaluate the benefits of IP
      10 as a triage approach to monitor ART in resource-limited settings.

PMID- 29020146
TI  - Trends in Pricing and Generic Competition Within the Oral Antibiotic Drug Market
      in the United States.
AB  - Background: In recent years, the price of many older generic drugs, including
      numerous antibiotics, has increased substantially. We sought to analyze recent
      price changes and extent of generic competition within a cohort of commonly
      prescribed off-patent oral antibiotics. Methods: We extracted oral antibiotics
      recommended for common outpatient conditions in the Infectious Diseases Society
      of America Practice Guidelines. We determined all US Food and Drug Administration
      approved manufacturers for each formulation and strength in 2013 and 2016 and the
      yearly national average drug acquisition cost (NADAC) price between 2013 and
      2016. Wilcoxon signed rank test was used to compare changes in drug prices and
      number of manufacturers from 2013 to 2016. Spearman correlation coefficient was
      used to assess the association between drug prices and number of manufacturers.
      Results: Twenty-two antibiotics (81 formulations and strengths) were analyzed.
      There was no change in the median NADAC price or the number of manufacturers
      between 2013 and 2016. However, 11 (14%) formulations increased in price by 90%
      or more, and 13 (16%) had 2 or fewer manufacturers during all 4 years. Antibiotic
      prices were negatively associated with the number of available manufacturers.
      Conclusions: While prices and the number of manufacturers for common oral
      antibiotics were overall stable between 2013 and 2016, reduced manufacturer
      competition was associated with increased prices. A subset of antibiotics
      exhibited substantial price increases, and most, but not all, had limited
      manufacturer competition. Policy solutions are needed to ensure availability of
      low-cost, essential generic antibiotics.

PMID- 29020147
TI  - Congenital Cytomegalovirus Infection: Improved Understanding of Maternal Immune
      Responses That Reduce the Risk of Transplacental Transmission.

PMID- 29020149
TI  - A Coordinated and Sustained Response to the Threat of Antibiotic Resistance Is
      Critical: Lessons Learned From Israel.

PMID- 29020148
TI  - Childhood Residential and Agricultural Pesticide Exposures in Relation to Adult
      Onset Rheumatoid Arthritis in Women.
AB  - Farming and pesticide exposure may influence risk of rheumatoid arthritis (RA);
      the role of early-life pesticide exposure is unknown. The Sister Study includes a
      US national cohort of women aged 35-74 years (enrolled 2004-2009); we examined
      childhood pesticide exposure in women in this cohort with adult-onset RA. Cases
      (n = 424) were compared with 48,919 noncases. Data included pesticide use at the
      longest childhood residence through age 14 years, farm residence of at least 12
      months with agricultural pesticide exposure through age 18 years, and maternal
      farm experience. Odds ratios and 95% confidence intervals were adjusted for age,
      race or ethnicity, education, smoking, and childhood socioeconomic factors. Cases
      with RA reported more frequent and direct (personal) residential pesticide use in
      childhood (for infrequent/indirect pesticide use, odds ratio (OR) = 1.1; for
      frequent/direct use, OR = 1.8; P for trend = 0.013). Compared with women without
      residential farm history, odds of having RA increased for those reporting a
      childhood-only farm residence with personal exposure to pesticides used on crops
      (OR = 1.8, 95% confidence interval: 1.1, 2.9) or livestock (OR = 2.0, 95%
      confidence interval: 1.2, 3.3). Our findings suggest adult-onset RA may be
      related to childhood exposure to residential and agricultural pesticides, and
      support further investigations of lifetime pesticide use in RA.

PMID- 29020151
TI  - Viruses Associated With Unexplained Acute Liver Failure: Next Generation Reveals
      the Last Generation.

PMID- 29020150
TI  - A Multicenter Study Evaluating Ceftriaxone and Benzathine Penicillin G as
      Treatment Agents for Early Syphilis in Jiangsu, China.
AB  - Background: The aim of this study was to assess the efficacy of ceftriaxone and
      benzathine penicillin G (BPG) in nonpregnant, immunocompetent adults with early
      syphilis because there is a lack of clinical evidence supporting ceftriaxone as
      an alternative treatment for early syphilis without an human immunodeficiency
      virus coinfection. Methods: A randomized, open-label controlled study evaluating
      the efficacy of ceftriaxone and BPG was conducted in 4 hospitals in Jiangsu
      Province. Treatment comprised either ceftriaxone (1.0 g, given intravenously,
      once daily for 10 days) or BPG (2.4 million units, given intramuscularly, once
      weekly for 2 weeks). A serological response was defined as a >=4-fold decline in
      the rapid plasma reagin (RPR) titer. Results: In all, 301 patients with early
      syphilis were enrolled in this study; 230 subjects completed the follow-ups. The
      serological response at 6 months of follow up was observed in 90.2% in
      ceftriaxone group and 78.0% in BPG group (P = .01). There was no significant
      difference between treatment groups in patients with primary or early latent
      syphilis, but among patients with secondary syphilis the difference was highly
      significant (95.8% vs 76.2%; P < .01). Moreover, patients exhibiting a Jarisch
      Herxheimer reaction after treatment might have a shorter period before a
      serological response (P = .03). Conclusions: In this study, ceftriaxone regimen
      was noninferior to the BPG regimen in nonpregnant, immunocompetent patients with
      early syphilis. Clinical Trials Registration: ChiCTR-TQR-13003624.

PMID- 29020152
TI  - Increases in Ocular Syphilis-North Carolina, 2014-2015.
AB  - Background: Ocular syphilis is an inflammatory eye disease due to Treponema
      pallidum infection. In the United States, syphilis rates have increased since
      2000; clusters of ocular syphilis were reported in 2015. We investigated ocular
      syphilis in North Carolina to describe the epidemiology and clinical course of
      disease. Methods: We reviewed syphilis cases reported to North Carolina during
      2014-2015 and abstracted information from health department interviews for cases
      with ocular symptoms and no other defined etiology. To assess duration and
      severity of ocular symptoms, we also reviewed medical records and conducted
      structured interviews. We compared the prevalence of ocular manifestations among
      reported syphilis cases by demographic and clinical characteristics. Results:
      Among 4232 syphilis patients, 63 (1.5%) had ocular syphilis: 21 in 2014 and 42 in
      2015, a 100% increase. Total syphilis cases increased 35% through 2015. No
      patient with ocular syphilis named another ocular syphilis patient as a sex
      partner. Patients presented in all syphilis stages; 24 (38%) were diagnosed in
      primary or secondary syphilis. Ocular manifestations were more prevalent among
      syphilis patients who were male, aged >=40 years, white, and infected with human
      immunodeficiency virus. No risk behaviors were associated with ocular syphilis.
      Among 39 interviewed patients, 34 (87%) reported reduced vision during infection;
      12 (31%) reported residual visual symptoms posttreatment. Conclusions: In North
      Carolina, ocular syphilis increased from 2014 to 2015 and may be due to increased
      recognition of ocular manifestations, or a true increase in ocular syphilis. Many
      ocular syphilis patients experienced vision loss; however, most improved
      posttreatment.

PMID- 29020154
TI  - Hospital Sinks Are a Potential Nosocomial Source of Candida Infections.

PMID- 29020153
TI  - Universal Screening With Use of Immunoglobulin G Avidity for Congenital
      Cytomegalovirus Infection.
AB  - Background: The aim of this prospective cohort study was to evaluate the efficacy
      of maternal screening for congenital cytomegalovirus infection (CCI) using
      cytomegalovirus (CMV) immunoglobulin G (IgG) and the IgG avidity index (AI).
      Methods: Pregnant women underwent screening of CMV IgG and AI measurements. IgG
      negative women underwent remeasurement of IgG after educational intervention.
      Women with an AI <=45% received further examinations, including measurement of
      CMV IgM. All newborns received polymerase chain reaction analyses of the urine,
      and CCI was diagnosed by the detection of CMV-DNA in the urine. Primary infection
      was defined as an AI <35% and/or positive IgM (>1.20 index). Serum samples from
      women with an AI >45% were stored, and the IgM levels were measured after
      delivery. The efficacy of AI and IgM for CCI screening was compared. Results: A
      total of 1562 (71.2%) women tested positive for IgG. In this study, 10 newborns
      with CCI were detected. The presence of infection in 3 newborns from mothers with
      primary infection was predicted by screening of IgG and AI <35%. However,
      infection in 7 newborns from women with nonprimary infection could not be
      predicted by screening of CMV IgG, AI <35%, or IgM. The application of an AI <35%
      for CCI screening yielded 22.2% sensitivity, 95.0% specificity, 2.5% positive
      predictive value, and 99.5% negative predictive value and was similar to that of
      IgM (11.1% sensitivity, 93.2% specificity, 0.9% positive predictive value, and
      92.7% negative predictive value). Conclusions: Maternal screening using CMV IgG
      and AI can identify pregnancies with CCI from primary infection, but overlooks a
      number of those from nonprimary infection.

PMID- 29020156
TI  - IDSA/AASLD Response to Cochrane Review on Direct-Acting Antivirals for Hepatitis
      C.

PMID- 29020157
TI  - Early Antibiotic Use After Fecal Microbiota Transplantation Increases Risk of
      Treatment Failure.
AB  - Antibiotic use within the first 8 weeks after fecal microbiota transplantation
      (FMT) may disrupt microbial engraftment and limit FMT effectiveness. We aimed to
      assess the burden of antibiotic use within 8 weeks of FMT and its impact on FMT
      efficacy.

PMID- 29020158
TI  - Modeling Risk-Factor Trajectories When Measurement Tools Change Sequentially
      During Follow-up in Cohort Studies: Application to Dietary Habits in Prodromal
      Dementia.
AB  - Modeling risk-factor trajectories is critical to understanding the natural
      history of diseases, yet the measurement tools used to assess risk factors often
      evolve during follow-up in cohorts, and such change prevents longitudinal
      analyses using standard models. We addressed this issue with a latent process
      model. Trajectories of average intakes of 5 food families (fish, meat, fruits,
      vegetables, and carbohydrate-rich foods) were described in prodromal dementia
      during the 10 years prior to diagnosis of cases and compared with those of
      controls, using a case-control sample nested within the Three-City Study,
      Bordeaux, France (1999-2012). Food intakes were measured by 2 or 3 different
      subquestionnaires across 5 repeated food frequency questionnaires. The sample
      comprised 205 incident cases and 410 controls matched for age, sex, education,
      and number of repeated food frequency questionnaires. Intakes of fish, fruits,
      and vegetables decreased at the approach of diagnosis among cases, suggesting
      reverse causation. This study demonstrated that the latent process model approach
      constitutes a powerful framework for modeling risk-factor trajectories, even when
      measurement tools change sequentially over time. Coupled with a case-control
      approach to contrast trajectories in prodromal disease versus healthy status, it
      can help us to understand the dynamic, causal relationships between risk factors
      and diseases.

PMID- 29020155
TI  - Measurement of Vitamin D for Epidemiologic and Clinical Research: Shining Light
      on a Complex Decision.
AB  - Vitamin D is a fat-soluble vitamin that is synthesized in the skin with exposure
      to sunlight or is ingested from dietary supplements or food. There has been a
      dramatic increase in research on vitamin D, linking it with health outcomes as
      varied as reproductive function, infection, cardiovascular disease, and cancer.
      The study of vitamin D has generated much excitement, partly because there is an
      ideal intervention: Low levels may be common and can be remedied with widely
      available supplements. Determination of vitamin D status is complex and has
      advanced dramatically in the past 5 years. In this paper, we begin by describing
      important considerations for measurement of total 25-hydroxyvitamin D (25(OH)D),
      the biomarker traditionally assessed in epidemiologic studies. While 25(OH)D
      remains the most commonly measured biomarker, emerging evidence suggests that
      other related analytes may contribute to the characterization of an individual's
      vitamin D status (e.g., vitamin D-binding protein, bioavailable and free 25(OH)D,
      the C-3 epimer of 25(OH)D, 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin
      D). The measurement of these analytes is also complex, and there are important
      considerations for deciding whether their measurement is warranted in new
      research studies. Herein we discuss these issues and provide the reader with an
      up-to-date synthesis of research on vitamin D measurement options and
      considerations.

PMID- 29020160
TI  - Immune Cross-Opsonization Within emm Clusters Following Group A Streptococcus
      Skin Infection: Broadening the Scope of Type-Specific Immunity.
AB  - Background: Group A Streptococcus (GAS) skin infections are particularly
      prevalent in developing nations. The GAS M protein, by which strains are
      differentiated into >220 different emm types, is immunogenic and elicits
      protective antibodies. A major obstacle for vaccine development has been the
      traditional understanding that immunity following infection is restricted to a
      single emm type. However, recent evidence has led to the hypothesis of immune
      cross-reactivity between emm types. Methods: We investigated the human
      serological response to GAS impetigo in Fijian schoolchildren, focusing on 3
      major emm clusters (E4, E6, and D4). Pre- and postinfection sera were assayed by
      enzyme-linked immunosorbent assay with N-terminal M peptides and bactericidal
      assays using the infecting-type strain, emm cluster-related strains, and
      nonrelated strains. Results: Twenty of the 53 paired sera demonstrated a >=4-fold
      increase in antibody titer against the infecting type. When tested against all
      cluster-related M peptides, we found that 9 of 17 (53%) paired sera had a >=4
      fold increase in antibody titer to cluster-related strains as well. When grouped
      by cluster, the mean change to cluster-related emm types in E4 and E6 was >4-fold
      (5.9-fold and 19.5-fold, respectively) but for D4 was 3.8-fold. The 17 paired
      sera were tested in bactericidal assays against selected cluster-related and
      nonrelated strains. While the responses were highly variable, numerous instances
      of cross-reactive killing were observed. Conclusions: These data demonstrate that
      M type-specific and cross-reactive immune responses occur following skin
      infection. The cross-reactive immune responses frequently align with emm
      clusters, raising new opportunities to design multivalent vaccines with broad
      coverage.

PMID- 29020159
TI  - Distinguishing Secondary Dengue Virus Infection From Zika Virus Infection With
      Previous Dengue by a Combination of 3 Simple Serological Tests.
AB  - Background: The explosive spread of Zika virus (ZIKV) and associated microcephaly
      present an urgent need for sensitive and specific serodiagnostic tests,
      particularly for pregnant women in dengue virus (DENV)-endemic regions. Recent
      reports of enhanced ZIKV replication by dengue-immune sera have raised concerns
      about the role of previous DENV infection on the risk and severity of
      microcephaly and other ZIKV complications. Methods: Enzyme-linked immunosorbent
      assays (ELISAs) based on ZIKV and DENV nonstructural protein 1 (NS1) were
      established to test acute, convalescent phase, and post-convalescent phase
      serum/plasma samples from reverse-transcription polymerase chain reaction
      confirmed cases including 20 primary ZIKV, 25 ZIKV with previous DENV, 58
      secondary DENV, and 16 primary DENV1 infections. Results: ZIKV-NS1 immunoglobulin
      M (IgM) and immunoglobulin G (IgG) ELISAs combined can detect ZIKV infection with
      a sensitivity of 95% and specificity of 66.7%. The ZIKV-NS1 IgG cross-reactivity
      by samples from secondary DENV infection cases ranged from 66.7% to 28.1% (within
      1 month to 1-2 years post-illness, respectively). Addition of DENV1-NS1 IgG ELISA
      can distinguish primary ZIKV infection; the ratio of absorbance of ZIKV-NS1 to
      DENV1-NS1 IgG ELISA can distinguish ZIKV with previous DENV and secondary DENV
      infections with a sensitivity of 87.5% and specificity of 81.3%. These findings
      were supported by analysis of sequential samples. Conclusions: An algorithm for
      ZIKV serodiagnosis based on 3 simple ELISAs is proposed to distinguish primary
      ZIKV, ZIKV with previous DENV, and secondary DENV infections; this could be
      applied to serodiagnosis for ZIKV, serosurveillance, and monitoring ZIKV
      infection during pregnancy to understand the epidemiology, pathogenesis, and
      complications of ZIKV in dengue-endemic regions.

PMID- 29020161
TI  - Comparison of Efficacy of Antimicrobial Agents Among Hospitalized Patients With
      Mycoplasma pneumoniae Pneumonia in Japan During Large Epidemics of Macrolide
      Resistant M. pneumoniae Infections: A Nationwide Observational Study.
AB  - Background: Mycoplasma pneumoniae strains with resistance to macrolides have been
      spreading worldwide. Here, we aimed to clarify which antimicrobial agent is a
      better treatment for patients with M. pneumoniae pneumonia in a setting with
      large epidemics of macrolide resistance. Methods: Adult patients hospitalized
      with laboratory-confirmed M. pneumoniae pneumonia from 2010 to 2013 were
      identified from the Japanese Diagnosis Procedure Combination national database.
      Drug switching, length of stay (LOS), 30-day mortality, and total costs for
      patients who underwent macrolide, quinolone, and tetracycline therapy were
      compared using propensity score analyses. Results: Eligible patients (N = 1650)
      from 602 hospitals were divided into the macrolide group (n = 508), quinolone
      group (n = 569), or tetracycline group (n = 573). We found that 52.8%, 21.8%, and
      38.6% of patients in the macrolide, quinolone, and tetracycline groups,
      respectively, had to switch drugs (P < .0001). There was no significant
      difference in the LOS and the 30-day mortality rates among these 3 groups. Cost
      was highest in the quinolone group (P = .0062). The propensity score-matched
      pairs (n = 487*2) generated from the quinolone and tetracycline groups also
      showed a lower proportion of patients who require switches in the quinolone group
      than in the tetracycline group (21.2% vs 39.6%, P < .0001) but not in the LOS,
      mortality, and cost. Conclusions: There were no significant differences in the
      LOS and mortality among any antimycoplasmal drugs as initial treatment for
      hospitalized M. pneumoniae pneumonia patients despite the lower switching rate in
      the quinolone group.

PMID- 29020162
TI  - Successful Therapy of a Multidrug-Resistant Extended-Spectrum beta-Lactamase
      Producing and Fluoroquinolone-Resistant Salmonella enterica Subspecies enterica
      Serovar Typhi Infection Using Combination Therapy of Meropenem and Fosfomycin.
AB  - We report a traveler who acquired a Salmonella enterica subspecies enterica
      serovar Typhi strain with resistance against beta-lactams, cephalosporins
      (extended-spectrum beta-lactamase-producing type SHV-12), and quinolones (plasmid
      mediated quinolone resistance gene qnrB7). After clinical deterioration using
      meropenem monotherapy, treatment success was achieved after commencement of
      fosfomycin in conjunction with high-dose meropenem. The case illustrates clinical
      challenges of multidrug-resistant S. Typhi.

PMID- 29020163
TI  - Influenza A(H5N1) Virus Infection in a Child With Encephalitis Complicated by
      Obstructive Hydrocephalus.
AB  - A 2-year-old boy with highly pathogenic avian influenza A(H5N1) virus infection
      with minimal respiratory symptoms developed encephalitis complicated by
      obstructive hydrocephalus. Viral RNA was detectable in cerebrospinal fluid. The
      virus belonged to H5N1 clade 2.3.2.1b and had acquired the mammalian adaptation
      mutation PB2 Q591K.

PMID- 29020165
TI  - Reply to Dilworth et al.

PMID- 29020164
TI  - Adults Hospitalized With Pneumonia in the United States: Incidence, Epidemiology,
      and Mortality.
AB  - Background: Understanding the burden of community-acquired pneumonia (CAP) is
      critical to allocate resources for prevention, management, and research. The
      objectives of this study were to define incidence, epidemiology, and mortality of
      adult patients hospitalized with CAP in the city of Louisville, and to estimate
      burden of CAP in the US adult population. Methods: This was a prospective
      population-based cohort study of adult residents in Louisville, Kentucky, from 1
      June 2014 to 31 May 2016. Consecutive hospitalized patients with CAP were
      enrolled at all adult hospitals in Louisville. The annual population-based CAP
      incidence was calculated. Geospatial epidemiology was used to define ecological
      associations among CAP and income level, race, and age. Mortality was evaluated
      during hospitalization and at 30 days, 6 months, and 1 year after
      hospitalization. Results: During the 2-year study, from a Louisville population
      of 587499 adults, 186384 hospitalizations occurred. A total of 7449 unique
      patients hospitalized with CAP were documented. The annual age-adjusted incidence
      was 649 patients hospitalized with CAP per 100000 adults (95% confidence
      interval, 628.2-669.8), corresponding to 1591825 annual adult CAP
      hospitalizations in the United States. Clusters of CAP cases were found in areas
      with low-income and black/African American populations. Mortality during
      hospitalization was 6.5%, corresponding to 102821 annual deaths in the United
      States. Mortality at 30 days, 6 months, and 1 year was 13.0%, 23.4%, and 30.6%,
      respectively. Conclusions: The estimated US burden of CAP is substantial, with
      >1.5 million unique adults being hospitalized annually, 100000 deaths occurring
      during hospitalization, and approximately 1 of 3 patients hospitalized with CAP
      dying within 1 year.

PMID- 29020167
TI  - Adjusting Expected Mortality Rates Using Information From a Control Population:
      An Example Using Socioeconomic Status.
AB  - Expected or reference mortality rates are commonly used in the calculation of
      measures such as relative survival in population-based cancer survival studies
      and standardized mortality ratios. These expected rates are usually presented
      according to age, sex, and calendar year. In certain situations, stratification
      of expected rates by other factors is required to avoid potential bias if
      interest lies in quantifying measures according to such factors as, for example,
      socioeconomic status. If data are not available on a population level,
      information from a control population could be used to adjust expected rates. We
      have presented two approaches for adjusting expected mortality rates using
      information from a control population: a Poisson generalized linear model and a
      flexible parametric survival model. We used a control group from BCBaSe-a
      register-based, matched breast cancer cohort in Sweden with diagnoses between
      1992 and 2012-to illustrate the two methods using socioeconomic status as a risk
      factor of interest. Results showed that Poisson and flexible parametric survival
      approaches estimate similar adjusted mortality rates according to socioeconomic
      status. Additional uncertainty involved in the methods to estimate stratified,
      expected mortality rates described in this study can be accounted for using a
      parametric bootstrap, but this might make little difference if using a large
      control population.

PMID- 29020166
TI  - Long-Term Impact of an Educational Antimicrobial Stewardship Program on Hospital
      Acquired Candidemia and Multidrug-Resistant Bloodstream Infections: A Quasi
      Experimental Study of Interrupted Time-Series Analysis.
AB  - Background: The global crisis of bacterial resistance urges the scientific
      community to implement intervention programs in healthcare facilities to promote
      an appropriate use of antibiotics. However, the clinical benefits or the impact
      on resistance of these interventions has not been definitively proved. Methods:
      We designed a quasi-experimental intervention study with an interrupted time
      series analysis. A multidisciplinary team conducted a multifaceted educational
      intervention in our tertiary-care hospital over a 5-year period. The main
      activity of the program consisted of peer-to-peer educational interviews between
      counselors and prescribers from all departments to reinforce the principles of
      the proper use of antibiotics. We assessed antibiotic consumption, incidence
      density of Candida and multidrug-resistant (MDR) bacteria bloodstream infections
      (BSIs) and their crude death rate per 1000 occupied bed days (OBDs). Results: A
      quick and intense reduction in antibiotic consumption occurred 6 months after the
      implementation of the intervention (change in level, -216.8 defined daily doses
      per 1000 OBDs; 95% confidence interval, -347.5 to -86.1), and was sustained
      during subsequent years (average reduction, -19,9%). In addition, the increasing
      trend observed in the preintervention period for the incidence density of
      candidemia and MDR BSI (+0.018 cases per 1000 OBDs per quarter; 95% confidence
      interval, -.003 to .039) reverted toward a decreasing trend of -0.130 per quarter
      (change in slope, -0.029; -.051 to -.008), and so did the mortality rate (change
      in slope, -0.015; -.021 to -.008). Conclusions: This education-based
      antimicrobial stewardship program was effective in decreasing the incidence and
      mortality rate of hospital-acquired candidemia and MDR BSI through sustained
      reduction in antibiotic use.

PMID- 29020170
TI  - Breast Cancer Incidence and Exposure to Metalworking Fluid in a Cohort of Female
      Autoworkers.
AB  - Breast cancer is the leading cancer diagnosed among women, and environmental
      studies have produced few leads on modifiable risk factors for breast cancer.
      Following an Institute of Medicine recommendation for occupational studies of
      women highly exposed to potential breast cancer risk factors, we took advantage
      of an existing cohort of 4,503 female autoworkers in Michigan exposed to
      metalworking fluid (MWF), complex mixtures of oils and chemicals widely used in
      metal manufacturing worldwide. Cox proportional hazards models were fit to
      estimate hazard ratios for incident breast cancer (follow-up, 1985-2013) and
      cumulative exposure (20-year lag) to straight mineral oils (a known human
      carcinogen) and water-based soluble and synthetic MWF. Because the state cancer
      registry began decades after the cohort was defined, we restricted our analyses
      to subcohorts of women hired closer to the start of follow-up. Among those hired
      after 1969, the hazard ratio associated with a 1 interquartile-range increase in
      straight MWF exposure was 1.13 (95% confidence interval: 1.03, 1.23). In separate
      analyses of premenopausal breast cancer, defined by age at diagnosis, the hazard
      ratio was elevated for exposure to synthetic MWF (chemical lubricants with no oil
      content), possibly suggesting a different mechanism in the younger women with
      breast cancer. This study adds to the limited literature regarding quantitative
      chemical exposures and breast cancer risk.

PMID- 29020169
TI  - Factors Associated With All-Cause Mortality Among Patients With Multidrug
      Resistant Tuberculosis-United States, 1993-2013.
AB  - We assessed characteristics associated with all-cause mortality among US patients
      with multidrug-resistant tuberculosis. Mortality decreased from 31% during 1993
      2002 to 11% during 2003-2013. Directly observed therapy coverage increased from
      74% to 95% and was protective against all-cause mortality after accounting for
      demographics, clinical characteristics, human immunodeficiency virus status, and
      period of treatment.

PMID- 29020168
TI  - Association of DNA Methylation-Based Biological Age With Health Risk Factors and
      Overall and Cause-Specific Mortality.
AB  - Measures of biological age based on blood DNA methylation, referred to as age
      acceleration (AA), have been developed. We examined whether AA was associated
      with health risk factors and overall and cause-specific mortality. At baseline
      (1990-1994), blood samples were drawn from 2,818 participants in the Melbourne
      Collaborative Cohort Study (Melbourne, Victoria, Australia). DNA methylation was
      determined using the Infinium HumanMethylation450 BeadChip array (Illumina Inc.,
      San Diego, California). Mixed-effects models were used to examine the association
      of AA with health risk factors. Cox models were used to assess the association of
      AA with mortality. A total of 831 deaths were observed during a median 10.7 years
      of follow-up. Associations of AA were observed with male sex, Greek nationality
      (country of birth), smoking, obesity, diabetes, lower education, and meat intake.
      AA measures were associated with increased mortality, and this was only partly
      accounted for by known determinants of health (hazard ratios were attenuated by
      20%-40%). Weak evidence of heterogeneity in the association was observed by sex
      (P = 0.06) and cause of death (P = 0.07) but not by other factors. DNA
      methylation-based AA measures are associated with several major health risk
      factors, but these do not fully explain the association between AA and mortality.
      Future research should investigate what genetic and environmental factors
      determine AA.

PMID- 29020171
TI  - Comparison of the Impact of Pneumococcal Conjugate Vaccine 10 or Pneumococcal
      Conjugate Vaccine 13 on Invasive Pneumococcal Disease in Equivalent Populations.
AB  - Background: Pneumococcal conjugate vaccine 10 (PCV10) and pneumococcal conjugate
      vaccine 13 (PCV13), are used in childhood immunization programs worldwide, but
      direct comparisons of impacts against invasive pneumococcal disease (IPD) in
      equivalent populations have not been performed. We compared the vaccines
      (prevaccination 2007-2009 vs postvaccination 2013-2016) in Sweden, where the 21
      counties use either PCV10 or PCV13 (introduced 2009-2010). Methods: All IPD
      episodes (n = 16992) were recorded in Sweden during 2005-2016. Of 14 186 isolates
      from 2007-2016, 13 468 (94.9%) were characterized with serotyping and 12 235
      (86.2%) with antibiotic susceptibility. Poisson models assessed changes in
      incidence over time. Results: Invasive pneumococcal disease incidences decreased
      between 2005 and 2016 in vaccinated children (by 68.5%), and in the whole
      population (by 13.5%), but not among the elderly (increased by 2%) due to a
      substantial increase in nonvaccine types (NVTs). In 2016, NVTs constituted 72% of
      IPD cases in the elderly. Serotype 6A declined in PCV10 and PCV13 counties,
      whereas serotype 19A increased in PCV10 counties. There was no effect against
      serotype 3. Cross-protection was found between 6B and 6A but not between 19F and
      19A. Serotype 6C increased in PCV10 counties, but not in PCV13 counties,
      suggesting cross-protection with 6A, which is included in PCV13. In the elderly,
      the increase in NVTs, excluding 6C, was more pronounced in PCV13 counties.
      Conclusions: The overall impact of IPD incidences was not statistically different
      irrespective of vaccine used. The incidence of serotypes, where the effect of the
      vaccines differed, will influence the cost-effectiveness of which vaccine to use
      in immunization programs. The dominance of NVTs suggests a limited effect of
      current pediatric PCVs against IPD in the elderly.

PMID- 29020172
TI  - Inadequacy of High-Dose Fluconazole Monotherapy Among Cerebrospinal Fluid
      Cryptococcal Antigen (CrAg)-Positive Human Immunodeficiency Virus-Infected
      Persons in an Ethiopian CrAg Screening Program.
AB  - A total of 817 human immunodeficiency virus-infected Ethiopians with CD4 <150
      cells/mL underwent plasma cryptococcal antigen (CRAG) screening. CRAG prevalence
      was 6.2%. Of participants with plasma CRAG titers >1:640, 96% (27 of 28) had
      cryptococcal meningitis (cerebrospinal fluid CRAG-positive) whereas 50% (7 of 14)
      with 1:160-1:320 titers had meningitis. With fluconazole 1200 mg/d therapy, 68%
      of meningitis patients (23 of 34) died within 3 months. Plasma CRAG titers >1:160
      predict meningitis, requiring more intensive antifungal therapy.

PMID- 29020175
TI  - Urinary Lipoarabinomannan Detection and Disseminated Nontuberculous Mycobacterial
      Disease.

PMID- 29020173
TI  - Time to Sputum Culture Conversion and Treatment Outcomes Among Patients with
      Isoniazid-Resistant Tuberculosis in Atlanta, Georgia.
AB  - Background: Although isoniazid-resistant tuberculosis is more common than
      multidrug-resistant tuberculosis, it has been much less studied. We examined the
      impact of isoniazid resistance and treatment regimen, including use of a
      fluoroquinolone, on clinical outcomes. Methods: A retrospective cohort study
      among patients with sputum culture-positive tuberculosis was performed. Early
      fluoroquinolone (FQ) use was defined as receiving >=5 doses during the first
      month of treatment. The primary outcome was time to sputum culture conversion
      (tSCC). A multivariate proportional hazards model was used to determine the
      association of isoniazid resistance with tSCC. Results: Among 236 patients with
      pulmonary tuberculosis, 59 (25%) had isoniazid resistance. The median tSCC was
      similar for isoniazid-resistant and -susceptible cases (35 vs 29 days; P = .39),
      and isoniazid resistance was not associated with tSCC in multivariate analysis
      (adjusted hazard ratio = 0.83; 95% confidence interval [CI], .59-1.17). Early FQ
      use was higher in isoniazid-resistant than -susceptible cases (20% vs 10%; P =
      .05); however, it was not significantly associated with tSCC in univariate
      analysis (hazard ratio = 1.48; 95% CI, .95-2.28). Patients with isoniazid
      resistant tuberculosis were treated with regimens containing rifampin,
      pyrazinamide, and ethambutol +/- a FQ for a median of 9.7 months. Overall, 191
      (83%) patients were cured. There was no difference in initial treatment outcomes;
      however, all cases of acquired-drug resistance (n = 1) and recurrence (n = 3)
      occurred among patients with isoniazid-resistant tuberculosis. Conclusions: There
      was no significant association with isoniazid resistance and tSCC or initial
      treatment outcomes. Although patients with isoniazid-resistant tuberculosis had a
      high cure rate, the cases of recurrence and acquired drug resistance are
      concerning and highlight the need for longer-term follow-up studies.

PMID- 29020176
TI  - DPP4, the Middle East Respiratory Syndrome Coronavirus Receptor, is Upregulated
      in Lungs of Smokers and Chronic Obstructive Pulmonary Disease Patients.
AB  - Background: Middle East respiratory syndrome coronavirus (MERS-CoV) causes
      pneumonia with a relatively high case fatality rate in humans. Smokers and
      chronic obstructive pulmonary disease (COPD) patients have been reported to be
      more susceptible to MERS-CoV infection. Here, we determined the expression of
      MERS-CoV receptor, dipeptidyl peptidase IV (DPP4), in lung tissues of smokers
      without airflow limitation and COPD patients in comparison to nonsmoking
      individuals (never-smokers). Methods: DPP4 expression was measured in lung tissue
      of lung resection specimens of never-smokers, smokers without airflow limitation,
      COPD GOLD stage II patients and in lung explants of end-stage COPD patients. Both
      control subjects and COPD patients were well phenotyped and age-matched. The mRNA
      expression was determined using qRT-PCR and protein expression was quantified
      using immunohistochemistry. Results: In smokers and subjects with COPD, both DPP4
      mRNA and protein expression were significantly higher compared to never-smokers.
      Additionally, we found that both DPP4 mRNA and protein expression were inversely
      correlated with lung function and diffusing capacity parameters. Conclusions: We
      provide evidence that DPP4 is upregulated in the lungs of smokers and COPD
      patients, which could partially explain why these individuals are more
      susceptible to MERS-CoV infection. These data also highlight a possible role of
      DPP4 in COPD pathogenesis.

PMID- 29020177
TI  - Reply to Vos et al.

PMID- 29020174
TI  - The Impact of Statin and Angiotensin-Converting Enzyme Inhibitor/Angiotensin
      Receptor Blocker Therapy on Cognitive Function in Adults With Human
      Immunodeficiency Virus Infection.
AB  - Background: Although statins, angiotensin-converting enzyme inhibitors (ACEI) or
      angiotensin receptor blockers (ARB) are generally well tolerated, the impact of
      these therapies individually or in combination on the change in neurocognitive
      function in persons with human immunodeficiency virus infection is unknown.
      Methods: The study included participants in the AIDS Clinical Trials Group
      Longitudinal Linked Randomized Trials cohort participants not receiving a statin
      or ACEI/ARB within 30 days of first neurologic assessment (baseline), with
      assessments by NPZ-3 (z score of averaged Trailmaking A and B tests and digit
      symbol test [DST]) from >=2 measurements. Marginal structural models estimated
      the causal effect of statin or ACEI/ARB initiation on neurocognitive function;
      initial constant slope was assumed during the first year of treatment and a
      second constant slope thereafter. Results: Of 3949 eligible participants, 16%
      started therapy with a statin, 11% with an ACEI/ARB, and 5% with both. Statin
      therapy had no significant effect on the composite NPZ-3 (primary outcome),
      Trailmaking B test, or DST. A small, nonsignificant positive effect on the
      Trailmaking A test was seen during year 1 (estimate, 0.088; 95% confidence
      interval, -.010 to .187; P = .08) and a small but significant negative effect (
      0.033; -.058 to -.009; P = .007) in each subsequent year. ACEI/ARB therapy had a
      significant negative effect on the DST (-0.117; 95% confidence interval, -.217 to
      .016; P = .02) during year 1 but minimal effect in subsequent years or on other
      neurocognitive domains. Conclusions: In summary, although modest declines in
      neurocognitive performance were seen in single domains with statin or ACEI/ARB
      therapy, we did not find consistent evidence that statins or ACEI/ARB have an
      effect on global neurocognitive function. Future studies should focus on long
      term neurocognitive effects.

PMID- 29020178
TI  - Uptake of Antibiotic Stewardship Programs in US Acute Care Hospitals: Findings
      From the 2015 National Healthcare Safety Network Annual Hospital Survey.
AB  - To assess uptake of the Centers for Disease Control and Prevention's Core
      Elements of Hospital Antibiotic Stewardship Programs, we analyzed stewardship
      practices as reported in the 2015 National Healthcare Safety Network's Annual
      Hospital Survey. Hospital uptake of all 7 core elements increased from 40.9% in
      2014 to 48.1% in 2015.

PMID- 29020179
TI  - The Household Influenza Vaccine Effectiveness Study: Lack of Antibody Response
      and Protection Following Receipt of 2014-2015 Influenza Vaccine.
AB  - Background: Antigenically drifted A(H3N2) viruses circulated extensively during
      the 2014-2015 influenza season. Vaccine effectiveness (VE) was low and not
      significant among outpatients but in a hospitalized population was 43%. At least
      one study paradoxically observed increased A(H3N2) infection among those
      vaccinated 3 consecutive years. Methods: We followed a cohort of 1341 individuals
      from 340 households. VE against laboratory-confirmed influenza was estimated.
      Hemagglutination-inhibition and neuraminidase-inhibition antibody titers were
      determined in subjects >=13 years. Results: Influenza A(H3N2) was identified in
      166 (12%) individuals and B(Yamagata) in 34 (2%). VE against A(H3N2) was -3% (95%
      confidence interval [CI]: -55%, 32%) and similarly ineffective between age
      groups; increased risk of infection was not observed among those vaccinated in 2
      or 3 previous years. VE against influenza B(Yamagata) was 57% (95% CI: -3%, 82%)
      but only significantly protective in children <9 years (87% [95% CI: 43%, 97%]).
      Less than 20% of older children and adults had >=4-fold antibody titer rise
      against influenza A(H3N2) and B antigens following vaccination; responses were
      surprisingly similar for antigens included in the vaccine and those similar to
      circulating viruses. Antibody against A/Hong Kong/4801/14, similar to circulating
      2014-2015 A(H3N2) viruses and included in the 2016-2017 vaccine, did not
      significantly predict protection. Conclusions: Absence of VE against A(H3N2) was
      consistent with circulation of antigenically drifted viruses; however, generally
      limited antibody response following vaccination is concerning even in the context
      of antigenic mismatch. Although 2014-2015 vaccines were not effective in
      preventing A(H3N2) infection, no increased susceptibility was detected among the
      repeatedly vaccinated.

PMID- 29020181
TI  - A Healthcare Improvement Intervention Combining Nucleic Acid Microarray Testing
      With Direct Physician Response for Management of Staphylococcus aureus
      Bacteremia.
AB  - Background: Nucleic acid microarray (NAM) testing for detection of Staphylococcus
      aureus bacteremia (SAB) and S. aureus resistance gene determinants can reduce
      time to targeted antibiotic administration. Evidence-based management of SAB
      includes bedside infectious diseases (ID) consultation. As a healthcare
      improvement initiative at our institution, with the goal of improving management
      and outcomes for subjects with SAB, we implemented NAM with a process for
      responding to positive NAM results by directly triggered, mandatory ID
      consultation. Methods: Preintervention, SAB was identified by traditional culture
      and results passively directed to antibiotic stewardship program (ASP)
      pharmacists. Postintervention, SAB in adult inpatients was identified by Verigene
      Gram-Positive Blood Culture test, results paged directly to ID fellow physicians,
      and consultation initiated immediately. In the new process, ASP assisted with
      management after the initial consultation. A single-center, retrospective, pre
      /postintervention analysis was performed. Results: One hundred six
      preintervention and 120 postintervention subjects were assessed. Time to ID
      consultation after notification of a positive blood culture decreased 26.0 hours
      (95% confidence interval [CI], 45.1 to 7.1 hours, P < .001) postintervention
      compared with preintervention. Time to initiation of targeted antibiotic
      decreased by a mean of 21.2 hours (95% CI, 31.4 to 11.0 hours, P < .001) and time
      to targeted antibiotics for methicillin-sensitive S. aureus decreased by a mean
      of 40.7 hours (95% CI, 58.0 to 23.5 hours, P < .001). The intervention was
      associated with lower in-hospital (13.2% to 5.8%, P = .047) and 30-day (17.9% to
      8.3%, P = .025) mortality. Conclusions: Compared with an ASP-directed response to
      traditionally detected SAB, an efficient physician response to NAM was associated
      with improved care and outcomes for SAB.

PMID- 29020182
TI  - The Manufacturers' Perspective on World Health Organization Prequalification of
      In Vitro Diagnostics.
AB  - In vitro diagnostic devices (IVDs) help clinicians determine specific conditions,
      monitor therapeutic efficacy, and prevent drug resistance development. While
      stringent regulatory authorities (SRAs) regulate IVDs in most high-income
      countries, regulatory authorities in many low- and middle-income countries
      (LMICs) are nonexistent or do not enforce rigorous standards. In 2010, the World
      Health Organization established its Prequalification of In Vitro Diagnostics
      (PQDx) program to ensure "access to safe, appropriate and affordable" IVDs,
      especially in LMICs with little or no domestic regulatory frameworks, thereby
      reaching underserved populations. However, challenges in PQDx policies and
      procedures include an overloaded pipeline, timelines not publicly available,
      confusion about which products PQDx focuses on, perceived burden for documenting
      changes to prequalified products, overlap with SRA approvals, and uncertainty
      around long-term financing. PQDx can maximize its impact by considering the
      perspective of IVD manufacturers; similarly, IVD manufacturers should exercise
      adequate quality control over their submissions and associated processes.

PMID- 29020180
TI  - Molecular Tracing of the Geographical Origin of Human Immunodeficiency Virus Type
      1 Infection and Patterns of Epidemic Spread Among Migrants Who Inject Drugs in
      Athens.
AB  - Background: High numbers of human immunodeficiency virus type 1 (HIV-1)
      infections among people who inject drugs (PWID) have been diagnosed in Athens,
      Greece, since 2011. We aimed to trace the geographic origin of HIV-1 infection
      for migrants who inject drugs and to investigate whether transmissions occur more
      frequently among migrants than among Greek nationals. Methods: Multiple cross
      sectional studies were pooled to assemble all persons diagnosed with HIV-1 in
      Greece between 1 January 2011 and 31 October 2014. Phylogenetic analyses used
      maximum likelihood estimation. The hypothesis of ethnic compartmentalization was
      tested by reconstructing ancestral states of characters at the tips using the
      criterion of parsimony over a set of bootstrap trees. Results: Of 2274 persons,
      38.4% were PWID. Phylogenetic analyses showed the existence of 4 major PWID
      specific local transmission networks (LTNs): CRF14_BG (437 [58.6%]), CRF35_AD
      (139 [18.6%]), subtype B (116 [15.6%]), and subtype A (54 [7.2%]). Of 184 non
      Greek PWID, 78.3% had been infected within the PWID-LTNs. For 173 (94.3%), the
      origin of their infection was assumed to be in Greece (postmigration). For PWID
      infected within LTNs, transmissions for subtype A and CRF14_BG occurred more
      frequently among migrants than would be expected by chance (phyloethnic study).
      Conclusions: Our analysis showed that the majority of infections among migrants
      occurred postmigration. The existence of significant transmission networking
      among migrants highlights that this population is a priority for HIV prevention.
      As molecular analysis can estimate the probable country of HIV infection, it can
      help to inform the design of public health strategies.

PMID- 29020183
TI  - Rapid Tests for Common Respiratory Viruses.

PMID- 29020186
TI  - Rabies Postexposure Prophylaxis Noncompletion After Dog Bites: Estimating the
      Unseen to Meet the Needs of the Underserved.
AB  - Postexposure prophylaxis (PEP) prevents human rabies and is accessible in
      Cambodia principally in Phnom Penh, the capital. Timely, affordable access to PEP
      is a challenge for the mainly rural population. We aimed to identify districts
      independently associated with PEP noncompletion to position frontline vaccination
      centers. We analyzed the 2009-2013 database at the Rabies Prevention Center at
      the Institut Pasteur du Cambodge, Phnom Penh. Logistic regressions identified
      nongeographic determinants of PEP noncompletion as well as the districts that
      were independently associated with noncompletion after adjustment for these
      determinants. The influence of distance by road was estimated using a boosted
      regression-trees model. We computed a population attributable fraction (rabies
      index (RI)) for each district and developed a map of this RI distribution. A
      cartographic analysis based on the statistic developed by Getis and Ord
      identified clusters of high-RI districts. Factors independently associated with
      noncompletion were patients' district of residence, male sex, age 15-49 years,
      initial visit during rice harvest, the dog's status (culled or disappeared), and
      a prescribed PEP protocol requiring more than 3 PEP sessions (4 or 5). Four
      clusters of high-RI districts were identified using this analytical strategy,
      which is applicable to many vaccination or other health services. Positioning
      frontline PEP centers in these districts could significantly widen access to
      timely and adequate PEP.

PMID- 29020184
TI  - Risk of Acute Liver Injury After Statin Initiation by Human Immunodeficiency
      Virus and Chronic Hepatitis C Virus Infection Status.
AB  - Background: Patients with human immunodeficiency virus (HIV) and/or chronic
      hepatitis C virus (HCV) infection may be prescribed statins as treatment for
      metabolic/cardiovascular disease, but it remains unclear if the risk of acute
      liver injury (ALI) is increased for statin initiators compared to nonusers in
      groups classified by HIV/HCV status. Methods: We conducted a cohort study to
      compare rates of ALI in statin initiators vs nonusers among 7686 HIV/HCV
      coinfected, 8155 HCV-monoinfected, 17739 HIV-monoinfected, and 36604 uninfected
      persons in the Veterans Aging Cohort Study (2000-2012). We determined development
      of (1) liver aminotransferases >200 U/L, (2) severe ALI (coagulopathy with
      hyperbilirubinemia), and (3) death, all within 18 months. Cox regression was used
      to determine propensity score-adjusted hazard ratios (HRs) with 95% confidence
      intervals (CIs) of outcomes in statin initiators compared to nonusers across the
      groups. Results: Among HIV/HCV-coinfected patients, statin initiators had lower
      risks of aminotransferase levels >200 U/L (HR, 0.66 [95% CI, .53-.83]), severe
      ALI (HR, 0.23 [95% CI, .12-.46]), and death (HR, 0.36 [95% CI, .28-.46]) compared
      with statin nonusers. In the setting of chronic HCV alone, statin initiators had
      reduced risks of aminotransferase elevations (HR, 0.57 [95% CI, .45-.72]), severe
      ALI (HR, 0.15 [95% CI, .06-.37]), and death (HR, 0.42 [95% CI, .32-.54]) than
      nonusers. Among HIV-monoinfected patients, statin initiators had lower risks of
      aminotransferase increases (HR, 0.52 [95% CI, .40-.66]), severe ALI (HR, 0.26
      [95% CI, .13-.55]), and death (HR, 0.19 [95% CI, .16-.23]) compared with
      nonusers. Results were similar among uninfected persons. Conclusions: Regardless
      of HIV and/or chronic HCV status, statin initiators had a lower risk of ALI and
      death within 18 months compared with statin nonusers.

PMID- 29020185
TI  - Stool Microbiota at Neutrophil Recovery Is Predictive for Severe Acute Graft vs
      Host Disease After Hematopoietic Cell Transplantation.
AB  - Background: Graft-versus-host disease (GVHD) is common after allogeneic
      hematopoietic cell transplantation (HCT). Risk for death from GVHD has been
      associated with low bacterial diversity in the stool microbiota early after
      transplant; however, the specific species associated with GVHD risk remain poorly
      defined. Methods: We prospectively collected serial weekly stool samples from 66
      patients who underwent HCT, starting pre-transplantation and continuing weekly
      until 100 days post-transplant, a total of 694 observations in HCT recipients. We
      used 16S rRNA gene polymerase chain reaction with degenerate primers, followed by
      high-throughput sequencing to assess the relative abundance of sequence reads
      from bacterial taxa in stool samples over time. Results: The gut microbiota was
      highly dynamic in HCT recipients, with loss and appearance of taxa common on
      short time scales. As in prior studies, GVHD was associated with lower alpha
      diversity of the stool microbiota. At neutrophil recovery post-HCT, the presence
      of oral Actinobacteria and oral Firmicutes in stool was positively correlated
      with subsequent GVHD; Lachnospiraceae were negatively correlated. A gradient of
      bacterial species (difference of the sum of the relative abundance of positive
      correlates minus the sum of the relative abundance of negative correlates) was
      most predictive (receiver operator characteristic area under the curve of 0.83)
      of subsequent severe acute GVHD. Conclusions: The stool microbiota around the
      time of neutrophil recovery post-HCT is predictive of subsequent development of
      severe acute GVHD in this study.

PMID- 29020187
TI  - Outbreak of Influenza A(H7N2) Among Cats in an Animal Shelter With Cat-to-Human
      Transmission-New York City, 2016.
AB  - We describe the first case of cat-to-human transmission of influenza A(H7N2), an
      avian-lineage influenza A virus, that occurred during an outbreak among cats in
      New York City animal shelters. We describe the public health response and
      investigation.

PMID- 29020188
TI  - Human Cytomegalovirus-Specific Memory CD4+ T-Cell Response and Its Correlation
      With Virus Transmission to the Fetus in Pregnant Women With Primary Infection.
AB  - Background: Primary human cytomegalovirus (HCMV) infection during pregnancy is
      the major cause of congenital viral sequelae. The HCMV-specific T-cell response
      may have a role in the prevention of virus transmission to the fetus. Methods:
      HCMV-specific memory T cells were investigated in the second month after primary
      infection onset in 44 pregnant women (15 transmitting the infection to the fetus)
      and 8 pregnant women with remote infection. Peripheral blood mononuclear cells
      were stimulated for 12 days with peptide pools of HCMV proteins IE-1, IE-2, and
      pp65, and subsequently restimulated for 24 hours with the same peptide pools in a
      cultured enzyme-linked immunospot (ELISPOT) assay. Results: In pregnant women
      with primary infection, the cultured ELISPOT assay detected a higher T-cell
      response to pp65 than to IE-1 or IE-2, whereas in remote infection pp65-, IE-1-,
      and IE-2-specific T cells were detected at comparable levels. During primary
      infection, the cultured ELISPOT response was mainly mediated by CD4+ T cells, and
      was lower than in remote infection. Strikingly, the cultured ELISPOT response to
      pp65 (but not to IE-1 or IE-2) was significantly higher in nontransmitting
      mothers. To detect other factors potentially associated with nontransmission,
      different serological parameters were analyzed. Only immunoglobulin G avidity
      index was higher in nontransmitting mothers, who showed also a lower DNAemia
      level. These 2 parameters remained associated with congenital infection in
      multivariate analysis. Conclusions: Determination of HCMV-specific T cells by
      cultured ELISPOT, in pregnant women with primary HCMV infection, in association
      with avidity index and DNAemia may help to assess the risk of HCMV fetal
      transmission.

PMID- 29020190
TI  - The Mental Health Benefits of Acquiring a Home in Older Age: A Fixed-Effects
      Analysis of Older US Adults.
AB  - Homeownership is consistently associated with better mental health, but whether
      becoming a homeowner in later in life has positive psychological benefits has
      not, to our knowledge, been examined. We assessed whether acquiring a home after
      age 50 years was associated with depression in a representative sample of older
      US adults. We used individual fixed-effects models based on data from 20,524
      respondents aged >=50 years from the Health and Retirement Study, who were
      interviewed biennially during 1993-2010. Depressive symptoms were measured using
      the 8-item Center for Epidemiologic Studies Depression Scale. Controlling for
      confounders, becoming a homeowner in later life predicted a decline in depressive
      symptoms in the same year (beta = -0.0768, 95% confidence interval (CI): -0.152, 
      0.007). The association remained significant after 2 years (beta = -0.0556, 95%
      CI: -0.134, -0.001) but weakened afterward. Buying a home for reasons associated
      with positive characteristics of the new house or neighborhood drove this
      association (beta = -0.426, 95% CI: -0.786, -0.066), while acquiring a home for
      reasons associated with characteristics of the previous home or neighborhood, the
      desire to be closer to relatives, downsizing, or upsizing did not predict mental
      health improvements. Findings suggest that there are small but significant
      benefits for mental health associated with acquiring a home in older age.

PMID- 29020189
TI  - Macrofilaricidal Efficacy of Repeated Doses of Ivermectin for the Treatment of
      River Blindness.
AB  - Background: Mass drug administration (MDA) with ivermectin is the cornerstone of
      efforts to eliminate human onchocerciasis by 2020 or 2025. The feasibility of
      elimination crucially depends on the effects of multiple ivermectin doses on
      Onchocerca volvulus. A single ivermectin (standard) dose clears the skin-dwelling
      microfilarial progeny of adult worms (macrofilariae) and temporarily impedes the
      release of such progeny by female macrofilariae, but a macrofilaricidal effect
      has been deemed minimal. Multiple doses of ivermectin may cumulatively and
      permanently reduce the fertility and shorten the lifespan of adult females.
      However, rigorous quantification of these effects necessitates interrogating
      longitudinal data on macrofilariae with suitably powerful analytical techniques.
      Methods: Using a novel mathematical modeling approach, we analyzed, at an
      individual participant level, longitudinal data on viability and fertility of
      female worms from the single most comprehensive multiple-dose clinical trial of
      ivermectin, comparing 3-monthly with annual treatments administered for 3 years
      in Cameroon. Results: Multiple doses of ivermectin have a partial
      macrofilaricidal and a modest permanent sterilizing effect after 4 or more
      consecutive treatments, even at routine MDA doses (150 ug/kg) and frequencies
      (annual). The life expectancy of adult O. volvulus is reduced by approximately
      50% and 70% after 3 years of annual or 3-monthly (quarterly) exposures to
      ivermectin. Conclusions: Our quantification of macrofilaricidal and sterilizing
      effects of ivermectin should be incorporated into transmission models to inform
      onchocerciasis elimination efforts in Africa and residual foci in Latin America.
      It also provides a framework to assess macrofilaricidal candidate drugs currently
      under development.

PMID- 29020192
TI  - Single-Dose Azithromycin for the Treatment of Haemophilus ducreyi Skin Ulcers in
      Papua New Guinea.
AB  - Background: Haemophilus ducreyi (HD) and Treponema pallidum subspecies pertenue
      (TP) are major causative agents of cutaneous ulcer (CU) in the tropics.
      Azithromycin is recommended to treat sexually transmitted HD infections and has
      good in vitro activity against HD strains from both genital and skin ulcers. We
      investigated the efficacy of oral single-dose azithromycin on HD-CU. Methods: We
      conducted a community-based cohort study in Lihir Island, Papua New Guinea, from
      October 2014 through May 2016. Consenting patients with skin ulcers >1 cm in
      diameter were eligible for this study and had collected a lesional swab for
      polymerase chain reaction (PCR). All participants were treated with single-dose
      azithromycin (30 mg/kg) and were followed up for assessment of clinical
      resolution. We retrospectively classified patients according to PCR results into
      HD, TP, and PCR-negative groups. The primary endpoint was healing rates of HD-CU
      at 14 days after treatment. Results: We obtained full outcome data from 246
      patients; 131 (53.3%) were HD PCR positive, 37 (15.0%) were TP positive, and 78
      (31.7%) were negative for all tests. Healing rates were 88.5% (95% confidence
      interval [CI], .82-.93) in the HD group, 78.4% [95% CI, .63-.89] in the TP group,
      and 74.4% (95% CI, .64-.83) in the PCR-negative group. If we included the
      participants with improved ulcers, the healing rates increased to 94.7%, 97.3%,
      and 89.7% respectively. HD cases classified as not healed all converted to HD
      negative PCR. Conclusions: Based upon clinical resolution and PCR conversion to
      HD negative, a single oral dose of azithromycin is efficacious for the treatment
      of HD-CU. These results have implications for the treatment of individual
      patients and for the use of antibiotics in public health strategies to control CU
      in the tropics.

PMID- 29020193
TI  - Generalizing Randomized Clinical Trial Results: Implementation and Challenges
      Related to Missing Data in the Target Population.
AB  - Statins are indicated in patients with elevated levels of high-sensitivity C
      reactive protein and normal low-density lipoprotein cholesterol based on results
      of the multicountry trial, Justification for the Use of Statins in Prevention: an
      Intervention Trial Evaluating Rosuvastatin (JUPITER) (2003-2008), but the benefit
      in real-world populations remains unknown. We sought to generalize JUPITER
      results to trial-eligible population using data from the UK Clinical Practice
      Research Datalink (CPRD), 2001-2014. We multiply imputed missing baseline
      characteristics for the CPRD population and selected the trial-eligible
      participants as the target population based on observed and imputed values. Trial
      participants were weighted to be representative of the CPRD population (n =
      383,418) based on individual predicted probability of selection into the trial.
      Trial participants were also standardized to the CPRD population without missing
      values (n = 2,677). In JUPITER, rosuvastatin reduced cardiovascular risk with a 3
      year risk difference of -2.0% (95% confidence interval (CI): -2.9, -1.1). The
      rosuvastatin effect was muted in the first 2 years but remained strong at 3 years
      after standardizing to the imputed CPRD population (3-year risk difference = 
      2.7%; 95% CI: -5.8, 0.4) and the CPRD population without missing data (3-year
      risk difference = -1.7%; 95% CI: -3.5, 0.1). The study serves as an illustration
      of possible approaches to understanding generalizability of trials using real
      world databases given limitations due to missing data on inclusion/exclusion
      criteria.

PMID- 29020194
TI  - Comparison of Measures of Adherence to Human Immunodeficiency Virus Preexposure
      Prophylaxis Among Adolescent and Young Men Who Have Sex With Men in the United
      States.
AB  - Background: Young men-who-have-sex-with-men (MSM) are disproportionately impacted
      by human immunodeficiency virus (HIV). Preexposure prophylaxis (PrEP) could
      reduce HIV acquisition among youth, but suboptimal adherence threatens
      effectiveness. Optimal metrics of PrEP adherence among adolescents have remain
      undefined. Methods: The Adolescent Trials Network 110/113 studies provided daily
      oral PrEP with tenofovir (TFV) disoproxil fumarate/emtricitabine over 48 weeks to
      a diverse population of MSM (aged 15-22 years). Self-reported adherence was
      assessed and PrEP drug concentrations measured from hair and dried blood spot
      (DBS) samples; 23% of participants received Wisepill electronic monitoring
      devices. The average number of PrEP doses per week taken was estimated, and
      concordance between measures assessed. Results: Among 243 participants, hair
      samples were collected at 1186/1238 (96%) person-visits. The concordance of TFV
      levels in hair and TFV-diphosphate in DBS around thresholds consistent with
      taking >=4 and 7 PrEP doses/week was high (76% and 80%). Hair and DBS
      concentrations correlated poorly with self-report and Wisepill metrics. Through
      week 12, 40%-60% of participants (by hair and DBS), <=31% (Wisepill), and >85%
      (self-report) were estimated to have taken >=4 PrEP doses/week (a threshold
      associated with protection among MSM). For all measures except self-report,
      adherence declined over time, with half of participants taking <2 doses/week by
      week 48. Conclusions: Among youth on PrEP, adherence waned over time. Self-report
      overestimated adherence, and use of Wisepill was limited. Hair collection was
      highly acceptable and provided similar interpretations to DBS. Incorporation of
      either metric in future PrEP studies among youth could identify suboptimal
      adherence and trigger interventions.

PMID- 29020191
TI  - QuantiFERON-TB Gold In-Tube as a Confirmatory Test for Tuberculin Skin Test in
      Tuberculosis Contact Tracing: A Noninferiority Clinical Trial.
AB  - Background: Screening strategies based on interferon-gamma release assays in
      tuberculosis contact tracing may reduce the need for preventive therapy without
      increasing subsequent active disease. Methods: We conducted an open-label,
      randomized trial to test the noninferiority of a 2-step strategy with the
      tuberculin skin test (TST) followed by QuantiFERON-TB Gold In-Tube (QFT-GIT) as a
      confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm)
      for targeting preventive therapy in household contacts of patients with
      tuberculosis. Participants were followed for 24 months after randomization. The
      primary endpoint was the development of tuberculosis, with a noninferiority
      margin of 1.5 percentage points. Results: A total of 871 contacts were
      randomized. Four contacts in the TST arm and 2 in the TST/QFT arm developed
      tuberculosis. In the modified intention-to-treat analysis, this accounted for
      0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5%
      confidence interval [CI], -1.86% to 0.90%); in the per-protocol analysis, the
      corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms,
      respectively (-0.85% difference; 97.5% CI, -3.14% to 1.43%). Of the 792 contacts
      analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with
      tuberculosis infection (23.1% difference; 95% CI, 16.4% to 30.0%). Conclusions:
      In low-incidence settings, screening household contacts with the TST and using
      QFT-GIT as a confirmatory test is not inferior to TST-alone for preventing active
      tuberculosis, allowing a safe reduction of preventive treatments. Clinical Trials
      Registration: NCT01223534.

PMID- 29020197
TI  - Sickle Cell Trait and Heat Injury Among US Army Soldiers.
AB  - There is concern that sickle cell trait (SCT) increases risk of exertional
      collapse, a primary cause of which is heat injury. However, to our knowledge, no
      population-based studies among active individuals have addressed this,
      representing a critical evidence gap. We conducted a retrospective cohort study
      of SCT-tested African-American soldiers who were on active duty in the US Army
      anytime between January 2011 and December 2014. Using Cox proportional hazards
      models and adjusting for demographic and medical factors, we observed no
      significant associations between SCT and either mild heat injury (hazard ratio
      (HR) = 1.15, 95% confidence interval (CI): 0.84, 1.56; n = 45,999) or heat stroke
      (HR = 1.11, 95% CI: 0.44, 2.79; n = 46,183). Risk of mild heat injury was
      substantially higher among soldiers with recent prescriptions for antipsychotic
      agents (HR = 3.25, 95% CI: 1.33, 7.90). Risk of heat stroke was elevated among
      those with a prior mild heat injury (HR = 17.7, 95% CI: 8.50, 36.7) and among
      overweight and obese individuals (HR = 2.91 (95% CI: 1.38, 6.17) and HR = 4.04
      (95% CI: 1.72, 9.45), respectively). In a setting where universal precautions are
      utilized to mitigate risk of exertion-related illnesses, SCT is not associated
      with either mild heat injury or heat stroke.

PMID- 29020195
TI  - Impact of Pneumococcal Conjugate Vaccines on Pneumonia Hospitalizations in High-
      and Low-Income Subpopulations in Brazil.
AB  - Background: Pneumococcal conjugate vaccines (PCVs) are being used worldwide. A
      key question is whether the impact of PCVs on pneumonia is similar in low- and
      high-income populations. However, most low-income countries, where the burden of
      disease is greatest, lack reliable data that can be used to evaluate the impact.
      Data from middle-income countries that have both low- and high-income
      subpopulations can provide a proxy measure for the impact of the vaccine in low
      income countries. Methods: We evaluated the impact of PCV10 on hospitalizations
      for all-cause pneumonia in Brazil, a middle-income country with localities that
      span a broad range of human development index (HDI) levels. We used complementary
      time series and spatiotemporal methods (synthetic controls and hierarchical
      Bayesian spatial regression) to test whether the decline in pneumonia
      hospitalizations associated with vaccine introduction varied across the
      socioeconomic spectrum. Results: We found that the declines in all-cause
      pneumonia hospitalizations in children and young and middle-aged adults did not
      vary substantially across low and high HDI subpopulations. Moreover, the
      estimated declines seen in infants and young adults were associated with higher
      levels of uptake of the vaccine at a local level. Conclusions: These results
      suggest that PCVs have an important impact on hospitalizations for all-cause
      pneumonia in both low- and high-income populations.

PMID- 29020196
TI  - The Risk and Predictors of Visceral Leishmaniasis Relapse in Human
      Immunodeficiency Virus-Coinfected Patients in Ethiopia: A Retrospective Cohort
      Study.
AB  - Background: East Africa, where Leishmania donovani is prevalent, faces the
      highest burden world-wide of visceral leishmaniasis (VL) and human
      immunodeficiency virus (HIV) coinfection. However, data on the risk and
      predictors of VL relapse are scarce. Such information is vital to target medical
      follow-up and interventions to those at highest risk. Methods: We conducted a
      retrospective cohort study at a Medecins Sans Frontieres-supported health center
      in northwest Ethiopia. We included adult VL-HIV coinfected patients treated for
      VL and discharged cured between February 2008 and February 2013. The risk of
      relapse was calculated using Kaplan-Meier methods, and predictors were determined
      using Cox regression models. Results: Of the 146 patients included, 140 (96%)
      were male and the median age was 31 years. At the index VL diagnosis, 110 (75%)
      had primary VL, 57 (40%) were on antiretroviral therapy (ART), and the median CD4
      count was 149 cells/uL. The median follow-up time after cure was 11 months,
      during which 44 (30%) patients relapsed. The risk of relapse was 15% at 6 months,
      26% at 12 months, and 35% at 24 months. Predictors of relapse were: not being on
      ART at VL diagnosis, ART not initiated during VL treatment, and high tissue
      parasite load (parasite grade 6+) at VL diagnosis. Conclusions: The risk of VL
      relapse in coinfected patients was high, particularly in those not on ART or
      presenting with a high tissue parasite load. These patients should be
      preferentially targeted for secondary prophylaxis and/or regular medical follow
      up. Timely ART initiation in all coinfected patients is crucial.

PMID- 29020198
TI  - A Cool Reception for Desirability of Outcome Ranking (DOOR)/Response Adjusted for
      Duration of Antibiotic Risk (RADAR) in Intra-abdominal Infections.

PMID- 29020199
TI  - Viral Surveillance in Serum Samples From Patients With Acute Liver Failure By
      Metagenomic Next-Generation Sequencing.
AB  - Background: Twelve percent of all acute liver failure (ALF) cases are of unknown
      origin, often termed indeterminate. A previously unrecognized hepatotropic virus
      has been suspected as a potential etiologic agent. Methods: We compared the
      performance of metagenomic next-generation sequencing (mNGS) with confirmatory
      nucleic acid testing (NAT) to routine clinical diagnostic testing in detection of
      known or novel viruses associated with ALF. Serum samples from 204 adult ALF
      patients collected from 1998 to 2010 as part of a nationwide registry were
      analyzed. One hundred eighty-seven patients (92%) were classified as
      indeterminate, while the remaining 17 patients (8%) served as controls, with
      infections by either hepatitis A virus or hepatitis B virus (HBV), or a
      noninfectious cause for their ALF. Results: Eight cases of infection from
      previously unrecognized viral pathogens were detected by mNGS (4 cases of herpes
      simplex virus type 1, including 1 case of coinfection with HBV, and 1 case each
      of HBV, parvovirus B19, cytomegalovirus, and human herpesvirus 7). Several missed
      dual or triple infections were also identified, and assembled viral genomes
      provided additional information on genotyping and drug resistance mutations.
      Importantly, no sequences corresponding to novel viruses were detected.
      Conclusions: These results suggest that ALF patients should be screened for the
      presence of uncommon viruses and coinfections, and that most cases of
      indeterminate ALF in the United States do not appear to be caused by novel viral
      pathogens. In the future, mNGS testing may be useful for comprehensive diagnosis
      of viruses associated with ALF, or to exclude infectious etiologies.

PMID- 29020200
TI  - The Effect of Female Sex on Hepatitis C Incidence Among People Who Inject Drugs:
      Results From the International Multicohort InC3 Collaborative.
AB  - Background: The objective of this study was to assess differences in hepatitis C
      virus (HCV) incidence by sex in people who inject drugs (PWID), using a large
      international multicohort set of pooled biological and behavioral data from
      prospective observational studies of incident human immunodeficiency virus (HIV)
      and HCV infections in high-risk cohorts (the InC3 Collaborative). Methods: HCV
      infection date was estimated based on a hierarchy of successive serological (anti
      HCV), virological (HCV RNA), and clinical (symptoms and/or liver function tests)
      data. We used a Cox proportional hazards model to calculate the crude and
      adjusted female to male (F:M) hazard ratio (HR) for HCV incidence using
      biological sex as the main exposure. Results: A total of 1868 PWID were observed
      over 3994 person-years of observation (PYO). Unadjusted F:M HR was 1.38 (95%
      confidence interval [CI], 1.15-1.65) and remained significant after adjusting for
      behavioral and demographic risk factors (1.39 [95% CI, 1.12-1.72]). Although
      syringe and equipment sharing were associated with the highest HCV incidence rate
      in women (41.62 and 36.83 PYO, respectively), we found no sex differences
      attributed to these risk factors. Conclusions: Our findings indicate that women
      who inject drugs may be at greater risk of HCV acquisition than men, independent
      of demographic characteristics and risk behaviors. Multiple factors, including
      biological (hormonal), social network, and differential access to prevention
      services, may contribute to increased HCV susceptibility in women who inject
      drugs.

PMID- 29020201
TI  - Novel Method Suggests Global Superiority of Short-Duration Antibiotics for Intra
      abdominal Infections.
AB  - Desirability of outcome ranking and response adjusted for duration of antibiotic
      risk (DOOR/RADAR) are novel and innovative methods of evaluating data in
      antibiotic trials. We analyzed data from a noninferiority trial of short-course
      antimicrobial therapy for intra-abdominal infection (STOP-IT), and results
      suggest global superiority of short-duration therapy for intra-abdominal
      infections.

PMID- 29020204
TI  - Linezolid-Resistant Enterococcus faecalis Infection Following Prolonged Low
      Dosage Linezolid Treatment for Multidrug-Resistant Tuberculosis.

PMID- 29020203
TI  - Empirical Antibiotic Treatment Does Not Improve Outcomes in Catheter-Associated
      Urinary Tract Infection: Prospective Cohort Study.
AB  - Background: Catheter associated urinary tract infection (CAUTI) is the most
      common healthcare-associated acquired infection. We aimed to describe the short-
      and long-term survival of patients with CAUTI and the impact of the empirical
      antibiotic treatment on survival rates. Methods: In this prospective
      observational study we included consecutive adult patients with a chronic
      indwelling catheter-associated UTI and sepsis hospitalized in medical
      departments. The primary outcomes were 30-days all-cause mortality and long-term
      survival at end of the follow-up. A multivariate analysis using logistic
      regression and Cox proportional hazard model was performed to identify
      independent risk factors for an adverse outcome. A propensity-score model for
      receiving appropriate empirical antibiotic therapy was constructed and used to
      match patients. Results: Overall, 315 consecutive patients with CAUTI were
      enrolled. The cohort consisted of elderly to very old patients (mean age 79.2 +/-
      11.5). The crude 30-day all-cause mortality rate was 30.8% (97/315). The median
      survival time was 82 days (interquartile range [IQR] 22-638). Appropriate early
      empirical treatment had no statistically significant association with 30-day
      mortality, propensity score-matched odds ratio (OR) 1.39 (0.76-2.55). Similarly,
      in the propensity-matched cohort, appropriate empirical treatment was not
      statistically associated with long-term survival (hazard ratio [HR] = 0.99, 95%
      confidence interval [CI] 0.75-1.3). Conclusions: In our setting, patients with
      CAUTI had poor short- and long-term prognosis regardless of appropriate empirical
      antibiotic treatment. Avoiding empirical antibiotics for CAUTI might be an
      important antibiotic stewardship intervention in hospitals.

PMID- 29020202
TI  - Rates of and Risk Factors for Adverse Drug Events in Outpatient Parenteral
      Antimicrobial Therapy.
AB  - Background: To better monitor patients on outpatient parenteral antimicrobial
      therapy (OPAT), we need an improved understanding of risk factors for and timing
      of OPAT-associated adverse drug events (ADEs). Methods: We analyzed a prospective
      cohort of patients on OPAT discharged from 2 academic medical centers. Patients
      underwent chart abstraction and a telephone survey. Multivariable analyses
      estimated adjusted incident rate ratios (aIRR) between clinical and demographic
      risk factors and clinician-determined clinically significant ADEs. Descriptive
      data were used to present patient-reported ADEs. Results: Of 339 patients
      enrolled in the study, 18.0% experienced an ADE (N = 65), of which 49 were
      significant (14.5%, 2.24/1000 home-OPAT days). Patients with longer courses of
      therapy had lower rates of ADEs compared with patients treated for 0-13 days (14
      27 days: aIRR, 0.44; 95% confidence interval [CI], 0.20-0.99; at least 28 days:
      aIRR, 0.11; 95% CI, 0.056-0.21). Risk factors for ADEs included female gender and
      receipt of daptomycin or vancomycin, while treatment for uncomplicated bacteremia
      and empiric treatment were associated with lower rates of ADEs. Conclusions: OPAT
      related ADEs were common and often occurred within 2 weeks of hospital discharge.
      Patients on OPAT should be monitored more closely for ADEs, including clinical
      assessment and laboratory monitoring, especially within the first weeks after
      hospital discharge and particularly among women and patients who receive
      vancomycin.

PMID- 29020205
TI  - Disability Among Ebola Survivors and Their Close Contacts in Sierra Leone: A
      Retrospective Case-Controlled Cohort Study.
AB  - Ebola survivors (21/27 [77.8%]) suffered more disability than their close
      contacts (6/54 [11.1%]) (adjusted odds ratio, 23.5 [95% confidence interval, 6.5
      85.7]; P < .001) when measured by the Washington Group Disability Extended
      Questionnaire. Major limitations in vision, mobility, cognition, and affect were
      observed in survivors 1 year following the 2014-2016 Ebola outbreak, highlighting
      the need for long-term rehabilitation.

PMID- 29020207
TI  - Dissecting Out the Direct Impacts of Large-Scale Antimicrobial Stewardship
      Interventions on Clinical Outcomes: Can Confounding Be Overcome?

PMID- 29020208
TI  - Optimizing Empiric Antibiotic Selection in Sepsis: Turning Probabilities Into
      Practice.

PMID- 29020206
TI  - Concordance With Prevention Guidelines and Subsequent Cancer, Cardiovascular
      Disease, and Mortality: A Longitudinal Study of Older Adults.
AB  - Reports on the associations between multiple clinical and behavioral health
      indicators and major health outcomes among older adults are scarce. We
      prospectively examined concordance with guidelines from the American Cancer
      Society and American Heart Association for disease prevention in relation to
      cancer, cardiovascular disease (CVD), and mortality among Cardiovascular Health
      Study enrollees aged 65-98 years who, at baseline assessment in 1989-1996 (n =
      3,491), were free of CVD and cancer. Total and cause-specific mortality, as well
      as incidence of cancer and CVD, were lower with higher guideline concordance.
      Independent of body mass index, blood pressure, total cholesterol, and fasting
      plasma glucose, better health behaviors (diet, physical activity, and alcohol
      consumption) were associated with lower mortality (2-sided P < 0.0001). Among
      individuals with ideal levels for 3-4 of these 4 cardiometabolic biomarkers,
      those with poor concordance with health behavior recommendations had higher
      mortality compared with those who had the highest concordance with these
      behavioral recommendations (adjusted mortality hazard ratio = 1.82, 95%
      confidence interval: 1.25, 2.67). Older adults who are concordant with
      recommendations for cancer and CVD prevention have reduced rates of chronic
      disease and mortality. Interventions to achieve and maintain healthy lifestyle
      behaviors may offer benefits both in the presence and absence of adverse
      traditional clinical risk factors.

PMID- 29020209
TI  - Demise of Polymerase Chain Reaction/Electrospray Ionization-Mass Spectrometry as
      an Infectious Diseases Diagnostic Tool.
AB  - Although there are several US Food and Drug Administration (FDA)-approved/cleared
      molecular microbiology diagnostics for direct analysis of patient samples, all
      are single target or panel-based tests. There is no FDA-approved/cleared
      diagnostic for broad microbial detection. Polymerase chain reaction
      (PCR)/electrospray ionization-mass spectrometry (PCR/ESI-MS), commercialized as
      the IRIDICA system (Abbott) and formerly PLEX-ID, had been under development for
      over a decade and had become CE-marked and commercially available in Europe in
      2014. Capable of detecting a large number of microorganisms, it was under review
      at the FDA when, in April 2017, Abbott discontinued it. This turn of events
      represents not only the loss of a potential diagnostic tool for infectious
      diseases but may be a harbinger of similar situations with other emerging and
      expensive microbial diagnostics, especially genomic tests.

PMID- 29020211
TI  - Reply to MacFadden et al.

PMID- 29020210
TI  - Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection
      Reduces Recurrent Urinary Tract Infection Frequency.
AB  - Broad-spectrum antibiotics for recurrent multidrug-resistant urinary tract
      infections (UTIs) disrupt the gut microbiome and promote antibiotic resistance.
      Fecal microbiota transplantation led to resolution of recurrent Clostridium
      difficile, significantly decreased recurrent UTI frequency, and improved
      antibiotic susceptibility profile of UTI-causing organisms.

PMID- 29020212
TI  - Screening Veterans for Syphilis: Implementation of the Reverse Sequence
      Algorithm.
AB  - We evaluated the syphilis reverse sequence algorithm (RSA) in a Veteran Affairs
      facility, finding 5.5% reactive Treponema pallidum enzyme immunoassay (EIA)
      tests. In a subset of EIA+/VDRL-/TP-PA+ cases, 48% were previously treated. Of
      veterans with unknown/no prior therapy, only 45% had documentation of subsequent
      treatment, suggesting suboptimal interpretation of RSA results.

PMID- 29020213
TI  - Improvement in Diagnosis of Histoplasma Meningitis by Combined Testing for
      Histoplasma Antigen and Immunoglobulin G and Immunoglobulin M Anti-Histoplasma
      Antibody in Cerebrospinal Fluid.
AB  - Background: Central nervous system (CNS) histoplasmosis is a life-threatening
      condition and represents a diagnostic and therapeutic challenge. Isolation of
      Histoplasma capsulatum from cerebrospinal fluid (CSF) or brain tissue is
      diagnostic; however, culture is insensitive and slow growth may result in
      significant treatment delay. We performed a retrospective multicenter study to
      evaluate the sensitivity and specificity of a new anti-Histoplasma antibody
      enzyme immunoassay (EIA) for the detection of IgG and IgM antibody in the CSF for
      diagnosis of CNS histoplasmosis, the primary objective of the study. The
      secondary objective was to determine the effect of improvements in the
      Histoplasma galactomannan antigen detection EIA on the diagnosis of Histoplasma
      meningitis. Methods: Residual CSF specimens from patients with Histoplasma
      meningitis and controls were tested for Histoplasma antigen and anti-Histoplasma
      immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody using assays developed
      at MiraVista Diagnostics. Results: A total of 50 cases and 157 controls were
      evaluated. Fifty percent of patients with CNS histoplasmosis were
      immunocompromised, 14% had other medical conditions, and 36% were healthy.
      Histoplasma antigen was detected in CSF in 78% of cases and the specificity was
      97%. Anti-Histoplasma IgG or IgM antibody was detected in 82% of cases and the
      specificity was 93%. The sensitivity of detection of antibody by currently
      available serologic testing including immunodiffusion and complement fixation was
      51% and the specificity was 96%. Testing for both CSF antigen and antibody by EIA
      was the most sensitive approach, detecting 98% of cases. Conclusions: Testing CSF
      for anti-Histoplasma IgG and IgM antibody complements antigen detection and
      improves the sensitivity for diagnosis of Histoplasma meningitis.

PMID- 29020214
TI  - How Well Do Neurologic Symptoms Identify Individuals With Neurosyphilis?
AB  - Background: Current guidelines recommend lumbar puncture (LP) in patients with
      syphilis who have neurologic symptoms. Methods: A total of 81 human
      immunodeficiency virus (HIV)-uninfected individuals and 385 HIV-infected
      individuals enrolled in a study of cerebrospinal fluid (CSF) abnormalities in
      syphilis underwent LP and a structured symptom history, including assessment of
      headache; stiff neck; photophobia; ocular inflammation; vision, hearing, or
      sensory loss; or gait incoordination. Neurosyphilis was defined as a reactive CSF
      Venereal Disease Research Laboratory (VDRL) test. Association between categorical
      variables was assessed using chi2, Fisher exact test, or logistic regression.
      Association between continuous and categorical variables was assessed using Mann
      Whitney U test. Results: CSF-VDRL was reactive in 20 (24.7%) HIV-uninfected and
      68 (17.7%) HIV-infected (P = .14) individuals. No symptom was more common in HIV
      uninfected individuals with neurosyphilis. Among the HIV-infected, the odds of a
      reactive CSF-VDRL were higher in those with mild or greater severity photophobia
      (2.0 [95% confidence interval [CI], 1.1-3.8]; P = .03), vision loss (2.3 [1.3
      4.1]; P = .003), or gait incoordination (2.4 [1.3-4.4]; P = .006); or moderate or
      greater severity hearing loss (3.1 [1.3-7.5]; P = .01). Diagnostic specificity of
      these 4 symptoms for neurosyphilis was high when limited to moderate or greater
      severity (91.6%-100%); however, the diagnostic sensitivity was low (1.5%-38.1%).
      Conclusions: Among HIV-infected patients with syphilis, 4 specific neurologic
      symptoms are more common in those with a reactive CSF-VDRL. Lack of symptoms does
      not guarantee that the CSF-VDRL is nonreactive, regardless of HIV status.

PMID- 29020215
TI  - Long-term Use of Proton Pump Inhibitors Is Associated With Increased Microbial
      Product Translocation, Innate Immune Activation, and Reduced Immunologic Recovery
      in Patients With Chronic Human Immunodeficiency Virus-1 Infection.
AB  - Background: Translocation of microbial products from the damaged gut causes
      increased immune activation in human immunodeficiency virus (HIV). Proton pump
      inhibitors (PPIs) predispose to bacterial overgrowth in the gut. We hypothesized
      that long-term use of PPIs is associated with greater microbial translocation and
      immune activation in HIV. Methods: HIV-infected persons on suppressive
      antiretroviral therapy (ART), including those receiving long-term PPIs (PPI+
      group) or not (PPI- group), were enrolled. We determined CD38+HLA-DR+CD8+
      (activated) T-cell frequency, and plasma levels of lipopolysaccharide (LPS), LPS
      binding protein (LBP), soluble CD14 (sCD14), and intestinal fatty acid binding
      protein (I-FABP). Results: We recruited 77 HIV-infected participants (37 PPI+ and
      40 PPI-) and 20 HIV-uninfected volunteers. PPI+ subjects were older and more
      likely to have hypertension and receive statins than PPI-. Nadir and enrollment
      CD4 counts, activated T-cells, and time on ART were similar in both groups. PPI+
      group had higher sCD14 (2.15 vs. 1.50 mcg/mL, P < .01), and LBP (21.78 vs. 18.28
      mcg/mL, P = .02) but lower I-FABP levels (608.5 vs. 2281.7 pg/mL, P = .05) than
      PPI-. In multivariate analysis, sCD14 levels remained associated with PPIs. In
      the year prior to enrollment, PPI+ group lost more CD4 cells than PPI- (-18 vs.
      54 cells/mm3, P = .03). HIV-infected subjects had higher immune activation and
      microbial translocation biomarkers than uninfected volunteers. Conclusion: In
      HIV, long-term use of PPIs was associated with increased microbial translocation,
      innate immune activation, and reduced immune reconstitution. Further studies are
      needed to evaluate the clinical implications of our findings. In the meantime,
      cautious use of PPIs is advised.

PMID- 29020216
TI  - Outpatient Management of Children With World Health Organization Chest Indrawing
      Pneumonia: Implementation Risks and Proposed Solutions.
AB  - This Viewpoints article details our recommendation for the World Health
      Organization Integrated Management of Childhood Illness guidelines to consider
      additional referral or daily monitoring criteria for children with chest
      indrawing pneumonia in low-resource settings. We review chest indrawing
      physiology in children and relate this to the risk of adverse pneumonia outcomes.
      We believe there is sufficient evidence to support referring or daily monitoring
      of children with chest indrawing pneumonia and signs of severe respiratory
      distress, oxygen saturation <93% (when not at high altitude), moderate
      malnutrition, or an unknown human immunodeficiency virus (HIV) status in an HIV
      endemic setting. Pulse oximetry screening should be routine and performed at the
      earliest point in the patient care pathway as possible. If outpatient clinics
      lack capacity to conduct pulse oximetry, nutritional assessment, or HIV testing,
      then we recommend considering referral to complete the evaluation. When referral
      is not possible, careful daily monitoring should be performed.

PMID- 29020217
TI  - Long-term Clinical Outcomes in Visceral Leishmaniasis/Human Immunodeficiency
      Virus-Coinfected Patients During and After Pentamidine Secondary Prophylaxis in
      Ethiopia: A Single-Arm Clinical Trial.
AB  - Background: We have conducted a single-arm trial evaluating monthly pentamidine
      secondary prophylaxis (PSP) to prevent visceral leishmaniasis (VL) relapse in
      Ethiopian human immunodeficiency virus-infected patients. Outcomes at 12 months
      of PSP have been previously reported, supporting PSP effectiveness and safety.
      However, remaining relapse-free after PSP discontinuation is vital. We now report
      outcomes and associated factors for a period of up to 2.5 years after initiating
      PSP, including 1-year follow-up after PSP discontinuation. Methods: The trial had
      3 phases: (1) 12 months of PSP; (2) a 6-month PSP extension period if CD4 count
      was <=200 cells/MUL at month 12; and (3) 12-month follow-up after stopping PSP.
      The probability of relapse and risk factors were calculated using Kaplan-Meier
      methods and Cox regression analysis. Results: For the 74 patients included, final
      study outcomes were as follows: 39 (53%) relapse-free, 20 (27%) relapsed, 5 (7%)
      deaths, 10 (14%) lost to follow-up. The 2-year risk of relapse was 36.9% (95%
      confidence interval, 23.4%-55.0%) and was highest for those with a history of VL
      relapse and low baseline CD4 count. Forty-five patients were relapse-free and in
      follow-up at month 12 of PSP. This included 28 patients with month 12 CD4 counts
      >200 cells/uL, remaining relapse-free after PSP discontinuation. Among the 17
      with month 12 CD4 count <200 cells/uL, 1 relapsed and 3 were lost during the PSP
      extension period. During 1-year post-PSP follow-up, 2 patients relapsed and 1 was
      lost to follow-up. No PSP-related serious adverse events were reported during the
      PSP-extension/post-PSP follow-up period. Conclusions: It seems safe to
      discontinue PSP at month 12 CD4 counts of >200 cells/uL. The management of those
      failing to reach this level remains to be defined. Clinical Trials Registration:
      NCT01360762.

PMID- 29020218
TI  - Pan-serotype Reduction in Progression of Streptococcus pneumoniae to Otitis Media
      After Rollout of Pneumococcal Conjugate Vaccines.
AB  - Background: Reductions in otitis media (OM) burden following rollout of
      pneumococcal conjugate vaccines (PCVs) have exceeded predictions of vaccine
      impact. In settings with active surveillance, reductions in OM caused by vaccine
      targeted pneumococcal serotypes have co-occurred with reductions in OM caused by
      other pathogens carried in the upper-respiratory tract of children. To understand
      these changes, we investigated the progression of vaccine-targeted and non
      vaccine pneumococcal serotypes from carriage to OM before and after vaccine
      rollout. Methods: Nasopharyngeal carriage prevalence of pneumococcus was
      monitored in prospective studies of Bedouin and Jewish children <3 years old in
      southern Israel between 2004 and 2016. Incidence of OM necessitating middle-ear
      fluid culture (predominantly complex OM including recurrent, spontaneously
      draining, non-responsive, and chronic cases) was monitored via prospective,
      population-based active surveillance. We estimated rates of pneumococcal serotype
      specific progression from carriage to disease before and after rollout of
      PCV7/13, measured as OM incidence per carrier. We pooled serotype-specific
      estimates using Bayesian random-effects models. Results: On average, rates of
      progression declined 92% (95% credible interval: 79-97%) and 80% (46-93%) for
      PCV7/13 serotypes among Bedouin and Jewish children <12 months old, respectively,
      and 32% (-58-71%) and 61% (-5-86%) among children aged 12-35m. For non-vaccine
      serotypes, rates of progression among Bedouin and Jewish children aged <12m
      declined 74% (55-85%) and 43% (4-68%), respectively. Conclusions: Vaccine
      targeted and non-vaccine pneumococcal serotypes showed lower rates of progression
      to complex OM after rollout of PCV7/13. Early-life OM episodes historically
      associated with vaccine-serotype pneumococci may impact the susceptibility of
      children to OM progression.

PMID- 29020219
TI  - Epidemiology and Antimicrobial Resistance Characteristics of the Sequence Type
      131-H30 Subclone Among Extraintestinal Escherichia coli Collected From US
      Children.
AB  - Background: Escherichia coli sequence type (ST) 131-H30 is a globally important
      pathogen implicated in rising rates of multidrug resistance among E. coli causing
      extraintestinal infections. Previous studies have focused on adults, leaving the
      epidemiology of H30 among children undefined. Methods: We used clinical data and
      isolates from a case-control study of extended-spectrum cephalosporin-resistant
      E. coli conducted at 4 US children's hospitals to estimate the burden and
      identify host correlates of infection with H30. H30 isolates were identified
      using 2-locus genotyping; host correlates were examined using log-binomial
      regression models stratified by extended-spectrum cephalosporin resistance
      status. Results: A total of 339 extended-spectrum cephalosporin-resistant and
      1008 extended-spectrum cephalosporin-susceptible E. coli isolates were available
      for analyses. The estimated period prevalence of H30 was 5.3% among all
      extraintestinal E. coli isolates (95% confidence interval [CI], 4.6%-7.1%); H30
      made up 43.3% (81/187) of extended-spectrum beta-lactamase (ESBL)-producing
      isolates in this study. Host correlates of infection with H30 differed by
      extended-spectrum cephalosporin resistance status: Among resistant isolates, age
      <=5 years was positively associated with H30 infection (relative risk [RR], 1.83
      [95% CI, 1.19-2.83]); among susceptible isolates, age <=5 years was negatively
      associated with H30 (RR, 0.48 [95% CI, .27-.87]), while presence of an underlying
      medical condition was positively associated (RR, 4.49 [95% CI, 2.43-8.31]).
      Conclusions: ST131-H30 is less common among extraintestinal E. coli collected
      from children compared to reported estimates among adults, possibly reflecting
      infrequent fluoroquinolone use in pediatrics; however, it is similarly dominant
      among ESBL-producing isolates. The H30 subclone appears to disproportionately
      affect young children relative to other extended-spectrum cephalosporin-resistant
      E. coli.

PMID- 29020220
TI  - Role of Secondary Prophylaxis With Valganciclovir in the Prevention of Recurrent
      Cytomegalovirus Disease in Solid Organ Transplant Recipients.
AB  - Background: Cytomegalovirus (CMV) is a major contributor to morbidity and
      mortality in solid organ transplant recipients (SOTRs). Ganciclovir and
      valganciclovir are highly effective antiviral drugs with a well-established role
      in primary prophylaxis and treatment of CMV disease. Our objective in this study
      was to examine the effect of secondary prophylaxis (SP) on the risk of relapse in
      SOTRs following an episode of CMV disease. Methods: We performed a retrospective
      cohort study of SOTRs from 1995 to 2015 and used propensity score-based inverse
      probability of treatment weighting methodology to control for confounding by
      indication. A weighted Cox model was created to determine the effect of SP on
      time to relapse within 1 year of treatment completion. Results: Fifty-two heart,
      34 liver, 79 kidney, and 5 liver-kidney transplant recipients who completed
      treatment for an episode of CMV infection/disease were included. A total of 120
      (70.6%) received SP (median duration, 61 days; range, 5-365) and 39 (23%)
      relapsed. SP was protective against relapse from 0 to 6 weeks following treatment
      completion (hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.05-0.69).
      However, after 6 weeks, risk of relapse did not significantly differ between the
      2 groups (HR, 1.18; 95% CI, 0.46-2.99). Conclusions: Our findings demonstrate
      that use of SP following treatment of CMV disease did not confer long-term
      protection against relapse, although it did delay relapse while patients were
      receiving antivirals. This suggests that SP has limited clinical utility in the
      overall prevention of recurrent CMV disease.

PMID- 29020223
TI  - Let's Make a Deal: Shortening the Solid Organ Transplant Waiting Time in Exchange
      for Transmitting and Treating Hepatitis C Infection in the Era of Safe and
      Effective Directly Acting Antivirals.

PMID- 29020222
TI  - Antimicrobial Resistance Gene Acquisition and Depletion Following Fecal
      Microbiota Transplantation for Recurrent Clostridium difficile Infection.
AB  - Fecal microbiota transplantation (FMT) may be a novel approach to eliminate
      multidrug-resistant bacteria from the gut and to prevent future infections. Using
      whole metagenome sequencing data from 8 FMT donor-recipient pairs, we identified
      37 and 95 antimicrobial resistance genes that were acquired by or removed from
      FMT recipients, respectively.

PMID- 29020221
TI  - Systemic Inflammatory Response to Malaria During Pregnancy Is Associated With
      Pregnancy Loss and Preterm Delivery.
AB  - Background: Pregnancy malaria (PM) is associated with a proinflammatory immune
      response characterized by increased levels of cytokines and chemokines such as
      tumor necrosis factor-alpha, interferon-gamma, interleukin 10 (IL-10), and CXCL9.
      These changes are associated with poor outcomes including low birthweight
      delivery and maternal anemia. However, it is unknown if inflammatory pathways
      during malaria are related to pregnancy loss and preterm delivery (PTD). Methods:
      Cytokine and chemokine levels were measured in maternal peripheral blood at
      enrollment, gestational week 30-32, and delivery, and in placental blood, of 638
      women during a longitudinal cohort study in Ouelessebougou, Mali. Plasmodium
      falciparum infection was assessed by blood smear microscopy at all visits.
      Results: PM was associated with increased levels of cytokines and chemokines
      including IL-10 and CXCL9. In a competing risks model adjusted for known
      covariates, high CXCL9 levels measured in the peripheral blood during pregnancy
      were associated with increased risk of pregnancy loss and PTD. At delivery, high
      IL-10 levels in maternal blood were associated with an increase in pregnancy
      loss, and increased IL-1beta levels in placental blood were associated with
      pregnancy loss and PTD. Conclusions: PM is associated with increased
      proinflammatory cytokine and chemokine levels in placental and maternal
      peripheral blood. Systemic inflammatory responses to malaria during pregnancy
      predict increased risk of pregnancy loss and PTD. Clinical Trials Registration:
      NCT01168271.

PMID- 29020224
TI  - Approach to the Investigation and Management of Patients With Candida auris, an
      Emerging Multidrug-Resistant Yeast.
AB  - Candida auris is an emerging, multidrug-resistant yeast that can spread in
      healthcare settings. It can cause invasive infections with high mortality and is
      difficult to identify using traditional yeast identification methods. Candida
      auris has been reported in more than a dozen countries, and as of August 2017,
      112 clinical cases have been reported in the United States. Candida auris can
      colonize skin and persist in the healthcare environment, allowing for
      transmission between patients. Prompt investigation and aggressive interventions,
      including notification to public health agencies, implementation of contact
      precautions, thorough environmental cleaning and disinfection, infection control
      assessments, contact tracing and screening of contacts to assess for
      colonization, and retrospective review of microbiology records and prospective
      surveillance for cases at laboratories are all needed to limit the spread of C.
      auris. This review summarizes the current recommended approach to manage cases
      and control transmission of C. auris in healthcare facilities.

PMID- 29020225
TI  - Fecal Microbiota Transplantation and Urinary Tract Infection: An Interesting
      Approach.

PMID- 29020228
TI  - The Impact of a Carbapenem-Resistant Enterobacteriaceae Outbreak on Facilitating
      Development of a National Infrastructure for Infection Control in Israel.
AB  - In 2006 the Israeli healthcare system faced an unprecedented outbreak of
      carbapenem-resistant Enterobacteriaceae, primarily involving KPC-producing
      Klebsiella pneumoniae clonal complex CC258. This public health crisis exposed
      major gaps in infection control. In response, Israel established a national
      infection control infrastructure. The steps taken to build this infrastructure
      and benefits realized from its creation are described here.

PMID- 29020229
TI  - Please, No More Gastric Aspirate to Diagnose Pulmonary Tuberculosis in Children.

PMID- 29020227
TI  - Rapid Detection of Powassan Virus in a Patient With Encephalitis by Metagenomic
      Sequencing.
AB  - We describe a patient with severe and progressive encephalitis of unknown
      etiology. We performed rapid metagenomic sequencing from cerebrospinal fluid and
      identified Powassan virus, an emerging tick-borne flavivirus that has been
      increasingly detected in the United States.

PMID- 29020226
TI  - Innate, T-, and B-Cell Responses in Acute Human Zika Patients.
AB  - Background: There is an urgent need for studies of viral persistence and immunity
      during human Zika infections to inform planning and conduct of vaccine clinical
      trials. Methods: In 5 returned US travelers with acute symptomatic Zika
      infection, clinical features, viral RNA levels, and immune responses were
      characterized. Results: Two pregnant, flavivirus-experienced patients had viral
      RNA persist in plasma for >44 and >26 days. Three days after symptom onset,
      transient increases in proinflammatory monocytes began followed at 5 days by
      transient decreases in myeloid dendritic cells. Anti-Zika virus immunoglobulin M
      was detected at day 7 after symptom onset, persisted beyond 103 days, and
      remained equivocal through day 172. Zika virus-specific plasmablasts and
      neutralizing antibodies developed quickly; dengue virus-specific plasmablasts and
      neutralizing antibodies at high titers developed only in flavivirus-experienced
      patients. Zika virus- and dengue virus-specific memory B cells developed in both
      flavivirus-naive and -experienced patients. CD4+ T cells were moderately
      activated and produced antiviral cytokines after stimulation with Zika virus C,
      prM, E, and NS5 peptides in 4/4 patients. In contrast, CD8+ T cells were
      massively activated, but virus-specific cells that produced cytokines were
      present in only 2/4 patients assessed. Conclusions: Acute infections with Zika
      virus modulated antigen-presenting cell populations early. Flavivirus-experienced
      patients quickly recalled cross-reactive MBCs to secrete antibodies. Dengue virus
      naive patients made little dengue-specific antibody but developed MBCs that cross
      reacted against dengue virus. Zika virus-specific functional CD4+ T cells were
      readily detected, but few CD8+ T cells specific for the tested peptides were
      found.

PMID- 29020231
TI  - Evidence of Sexually Transmitted Disease Testing Outside of Primary Human
      Immunodeficiency Virus Care for People Living With Human Immunodeficiency Virus
      in San Francisco, California.

PMID- 29020230
TI  - Effect of Maternally Derived Anti-protein and Anticapsular IgG Antibodies on the
      Rate of Acquisition of Nasopharyngeal Carriage of Pneumococcus in Newborns.
AB  - Background: In developing countries, introduction of pneumococcal conjugate
      vaccine has not eliminated circulation of vaccine serotypes. Vaccinating pregnant
      mothers to increase antibody concentrations in their newborn infants may reduce
      the acquisition of pneumococcal carriage and subsequent risk of disease. We
      explored the efficacy of passive immunity, attributable to anti-protein and
      anticapsular pneumococcal antibodies, against acquisition of carriage. Methods:
      We examined the rate of nasopharyngeal acquisition of pneumococci in the first 90
      days of life associated with varying anticapsular and anti-protein antibody
      concentrations in infant cord/maternal venous blood in Kilifi, Kenya. We used
      multivariable Cox proportional hazard models to estimate continuous functions
      relating acquisition of nasopharyngeal carriage to the concentration of
      maternally derived antibody. Results: Cord blood or maternal venous samples were
      collected from 976 mother-infant pairs. Pneumococci were acquired 561 times
      during 33,905 person-days of follow-up. Increasing concentrations of anti-protein
      antibodies were associated with either a reduction (PhtD1, PspAFam2, Spr0096,
      StkP) or, paradoxically, an increase (CbpA, LytC, PcpA, PiaA, PspAFam1, RrgBT4)
      in acquisition rate. We observed a nonsignificant reduction in the incidence of
      homologous carriage acquisition with high concentrations of maternally derived
      anticapsular antibodies to 5 serotypes (6A, 6B, 14, 19F, and 23F). Conclusion:
      The protective efficacy of several anti-protein antibodies supports the strategy
      of maternal vaccination to protect young infants from carriage and invasive
      disease. We were not able to demonstrate that passive anticapsular antibodies
      were protective against carriage acquisition at naturally occurring
      concentrations though it remains possible they may do so at the higher
      concentrations elicited by vaccination.

PMID- 29020233
TI  - Effectiveness of Intramuscular Immunoglobulin in Unvaccinated Family Members
      After Household Measles Exposure.

PMID- 29020234
TI  - Should the Aminoglycoside beta-Lactam Combination Be Abandoned in All Severely
      Ill Patients With Presumed Gram-Negative Infection?

PMID- 29020235
TI  - Redefining Human Immunodeficiency Virus (HIV) Preexposure Prophylaxis Failures.

PMID- 29020236
TI  - Signalling the risk of sudden cardiac death: the ECG and beyond.

PMID- 29020232
TI  - Staging classification of aortic stenosis based on the extent of cardiac damage.
AB  - Aims: In patients with aortic stenosis (AS), risk stratification for aortic valve
      replacement (AVR) relies mainly on valve-related factors, symptoms and co
      morbidities. We sought to evaluate the prognostic impact of a newly-defined
      staging classification characterizing the extent of extravalvular (extra-aortic
      valve) cardiac damage among patients with severe AS undergoing AVR. Methods and
      results: Patients with severe AS from the PARTNER 2 trials were pooled and
      classified according to the presence or absence of cardiac damage as detected by
      echocardiography prior to AVR: no extravalvular cardiac damage (Stage 0), left
      ventricular damage (Stage 1), left atrial or mitral valve damage (Stage 2),
      pulmonary vasculature or tricuspid valve damage (Stage 3), or right ventricular
      damage (Stage 4). One-year outcomes were compared using Kaplan-Meier techniques
      and multivariable Cox proportional hazards models were used to identify 1-year
      predictors of mortality. In 1661 patients with sufficient echocardiographic data
      to allow staging, 47 (2.8%) patients were classified as Stage 0, 212 (12.8%) as
      Stage 1, 844 (50.8%) as Stage 2, 413 (24.9%) as Stage 3, and 145 (8.7%) as Stage
      4. One-year mortality was 4.4% in Stage 0, 9.2% in Stage 1, 14.4% in Stage 2,
      21.3% in Stage 3, and 24.5% in Stage 4 (Ptrend < 0.0001). The extent of cardiac
      damage was independently associated with increased mortality after AVR (HR 1.46
      per each increment in stage, 95% confidence interval 1.27-1.67, P < 0.0001).
      Conclusion: This newly described staging classification objectively characterizes
      the extent of cardiac damage associated with AS and has important prognostic
      implications for clinical outcomes after AVR.

PMID- 29020237
TI  - Human Immunodeficiency Virus-Associated Chronic Lung Disease in Children and
      Adolescents in Zimbabwe: Chest Radiographic and High-Resolution Computed
      Tomographic Findings.
AB  - Background: Chronic respiratory symptoms are common among children living with
      human immunodeficiency virus (HIV). We investigated the radiological features of
      chronic lung disease in children aged 6-16 years receiving antiretroviral therapy
      for >=6 months in Harare, Zimbabwe. Methods: Consecutive participants from a HIV
      clinic underwent clinical assessment and chest radiography. Participants with an
      abnormal chest radiograph (assessed by a clinician) and/or those meeting a
      clinical case definition for chronic lung disease underwent high-resolution
      computed tomography (HRCT). Radiological studies were scored independently and
      blindly by 2 thoracic radiologists. Relationships between radiological
      abnormalities and lung function were examined. Results: Among 193 participants
      (46% female; median age, 11.2 years; interquartile range, 9.0-12.8 years), the
      median CD4 cell count was 720/uL (473-947/uL), and 79% had a human
      immunodeficiency virus (HIV) load of <400 copies/mL. The most common chest
      radiographic finding was ring/tramline opacities (55 of 193 participants; 29%).
      HRCT scans were evaluated in 84 participants (69%); decreased attenuation
      (present in 43%) was the dominant abnormality seen. The extent of decreased
      attenuation was strongly correlated with both the severity and extent of
      bronchiectasis (rs = 0.68 and P < .001 for both). The extent of decreased
      attenuation was also negatively correlated with forced expiratory volume in first
      second of expiration (rs = -0.52), forced vital capacity (rs = -0.42), and forced
      expiratory flow, midexpiratory phase (rs = -0.42) (P < .001 for all).
      Conclusions: The HRCT findings strongly suggest that obliterative bronchiolitis
      may be the major cause of chronic lung disease in our cohort. Further studies to
      understand the pathogenesis and natural history are urgently needed.

PMID- 29020240
TI  - Too Early to Recommend Early Fecal Microbiota Transplantation in Patients With
      Severe Clostridium difficile Infection, or Not Too Early?

PMID- 29020238
TI  - Acute Retinal Necrosis Caused by the Zoster Vaccine Virus.
AB  - We report acute retinal necrosis caused by the vaccine Oka strain following
      immunization of a 78-year-old woman with live zoster vaccine. Whole genome
      sequencing confirmed the ocular vOka strain to be derived from the vaccine and
      excluded the presence of new mutations or recombination with wild-type Varicella
      zoster virus.

PMID- 29020242
TI  - Successful transcatheter aortic valve-in-valve implantation in a patient having a
      chronic type A aortic dissection.

PMID- 29020239
TI  - Reproductive Aging and Hepatic Fibrosis Progression in Human Immunodeficiency
      Virus/Hepatitis C Virus-Coinfected Women.
AB  - Background: Severity of hepatic fibrosis is greater in postmenopausal than in
      premenopausal women, perhaps owing to protective effects of estrogens. However,
      prior studies of estrogen and liver fibrosis lack serial fibrosis measures,
      adjustment for age, or longitudinal observations in coinfected populations.
      Methods: In a longitudinal cohort of women coinfected with human immunodeficiency
      virus (HIV) and hepatitis C virus (HCV), we assessed fibrosis progression across
      reproductive age, using validated serum fibrosis markers, aminotransferase
      platelet ratio index (APRI) and fibrosis 4 (FIB-4). Fibrosis rate was evaluated
      within each woman as she transitioned from pre- to postmenopause, defined by a
      biomarker of ovarian function. Results: The median follow-up (n = 405) was 9.1
      years (interquartile range, 5.0-15.2 years), with a median menopausal age of 49
      years (47-52 years). When fully controlled for chronologic aging, the fibrosis
      progression rate was accelerated during perimenopause, as shown using FIB-4 (0.12
      units per year faster than during premenopause; 95% confidence interval [CI], .02
      .21; P = .01) and APRI (0.05 units per year faster; -.002 to .09; P = .06).
      Accelerated fibrosis was also observed during postmenopause compared with
      premenopause, for FIB-4 (0.14 units per year faster; 95% CI, -.01 to .29; P =
      .07) and APRI (0.07 units per year faster; -.003 to .15; P = .06). Accelerated
      fibrosis in perimenopause persisted after adjustment for Hispanic ethnicity,
      antiretroviral use, and alcohol (0.10 FIB-4 units per year faster than during
      premenopause; 95% CI, .008-.20; P = .03). Conclusions: In HIV/HCV-coinfected
      women, hepatic fibrosis accelerates with reproductive aging. Accelerated fibrosis
      begins in perimenopause, highlighting a previously unrecognized group of women at
      increased risk for advanced fibrosis and associated complications. Longitudinal
      analyses of fibrosis rates across reproductive age should be conducted in non-HCV
      related liver diseases, given potential implications in a broader spectrum of
      women.

PMID- 29020241
TI  - Infections, atherosclerosis, and coronary heart disease.
AB  - Atherosclerosis is a chronic inflammatory disease. Pathophysiological
      similarities between chronic infections and atherosclerosis triggered interest in
      a clinical association between these conditions. Various infectious microbes have
      been linked to atherosclerotic vascular disease in epidemiological studies.
      However, this association failed to satisfy the Koch's postulates of causation
      with multiple clinical trials demonstrating inefficacy of anti-infective
      therapies in mitigating atherosclerotic cardiovascular events. Identification of
      underlying pathophysiological mechanisms and experience with vaccination against
      various infectious agents has ushered a new avenue of efforts in the development
      of an anti-atherosclerotic vaccine. Studies in animal models have identified
      various innate and adaptive immune pathways in atherosclerosis. In this review,
      we discuss the patho-biological link between chronic infections and
      atherosclerosis, evaluate existing evidence of animal and human trials on the
      association between infections and cardiovascular disease and introduce the
      concept of an anti-atherosclerotic vaccine.

PMID- 29020243
TI  - Linking the sympathetic nervous system to the inflammasome: towards new
      therapeutics for atherosclerotic cardiovascular disease.

PMID- 29020244
TI  - Impact of total occlusion of culprit artery in acute non-ST elevation myocardial
      infarction: a systematic review and meta-analysis.
AB  - Aims: Total occlusion (TO) of the culprit artery usually presents with ST
      elevation myocardial infarction. A subset of patients with TO present as non-ST
      segment elevation myocardial infarction (NSTEMI) without classic ST-elevation on
      the electrocardiogram. This may lead to delay in identification of these patients
      and further management. We performed a meta-analysis to estimate the difference
      in outcomes between totally occluded and non-occluded culprit arteries in
      patients with NSTEMI. Methods and results: Our literature search yielded seven
      studies with 40 777 patients. The outcomes assessed were clinical presentation
      (Killip class), left ventricular ejection fraction, time to angiography, major
      cardiac adverse events (MACE) and all-cause mortality. The generic inverse or
      Mantel-Haenszel method was used to pool relevant outcomes and the mean difference
      (MD) or relative risk (RR) was calculated. A total of 10 415 (25.5%) patients had
      an occluded culprit artery with a predominant infero-lateral distribution (40%
      right coronary and 33% left circumflex artery). There was an increased risk of
      both MACE (short-term RR: 1.41; CI: 1.17, 1.70; P = 0.0003; I2 = 26%; medium- to
      long-term RR: 1.32; CI: 1.11, 1.56; P = 0.001; I2 = 25%) and all-cause mortality
      (short-term RR: 1.67; CI: 1.31, 2.13; P < 0.0001; I2 = 41%; medium to long-term
      RR: 1.42; CI: 1.08, 1.86; P = 0.01; I2 = 32%) with TO of the culprit artery.
      Conclusion: Our meta-analysis suggests that patients with NSTEMI who demonstrate
      a totally occluded culprit vessel on coronary angiography are at higher risk of
      mortality and major adverse cardiac events. Better risk stratification tools are
      needed to identify such high-risk acute coronary syndrome patients to facilitate
      earlier revascularization and potentially to improve outcomes.

PMID- 29020246
TI  - Addressing the Unknowns of Antimicrobial Resistance: Quantifying and Mapping the
      Drivers of Burden.
AB  - The global threat of antimicrobial resistance (AMR) has arisen through a network
      of complex interacting factors. Many different sources and transmission pathways
      contribute to the ever-growing burden of AMR in our clinical settings. The lack
      of data on these mechanisms and the relative importance of different factors
      causing the emergence and spread of AMR hampers our global efforts to effectively
      manage the risks. Importantly, we have little quantitative knowledge on the
      relative contributions of these sources and are likely to be targeting our
      interventions suboptimally as a result. Here we propose a systems mapping
      approach to address the urgent need for reliable and timely data to strengthen
      the response to AMR.

PMID- 29020245
TI  - Guillain-Barre Syndrome Associated With Zika Virus Infection in Martinique in
      2016: A Prospective Study.
AB  - Background: Guillain-Barre syndrome (GBS) has been reported to be associated with
      Zika virus (ZIKV) infection in case reports and retrospective studies, mostly on
      the basis of serological tests, with the problematic cross-reacting antibodies of
      the Flavivirus genus. Some GBS cases do not exhibit a high level of diagnostic
      certainty. This prospective study aimed to describe the clinical profiles and the
      frequency of GBS associated with ZIKV during the ZIKV outbreak in Martinique in
      2016. Methods: We recorded prospective data from GBS meeting levels 1 or 2 of
      diagnostic certainty for the Brighton Collaboration, with proof of recent ZIKV
      infection and negative screening for etiologies of GBS. Results: Of the sample of
      34 patients with suspected GBS during the outbreak, 30 had a proven presence of
      GBS, and 23 had a recent ZIKV infection. The estimated GBS incidence rate ratio
      (2016 vs 2006-2015) was 4.52 (95% confidence interval, 2.80-7.64; P = .0001).
      Recent ZIKV infection was confirmed by urine reverse-transcription polymerase
      chain reaction (RT-PCR) analysis in 17 cases and by serology in 6 cases.
      Patients, 65% of whom were male, had a median age of 61 years (interquartile
      range, 56-71 years) and experienced severe GBS. Electrophysiological tests were
      consistent with the primary demyelinating form of the disease. Conclusions: ZIKV
      infection is usually benign, when symptomatic, but in countries at risk of ZIKV
      epidemics, adequate intensive care bed capacity is required for management of
      severe GBS cases. Arbovirus RNA detection by RT-PCR should be part of the
      management of GBS cases.

PMID- 29020248
TI  - Relationship between microvascular obstruction and adverse events following
      primary percutaneous coronary intervention for ST-segment elevation myocardial
      infarction: an individual patient data pooled analysis from seven randomized
      trials.
AB  - Aims: Microvascular obstruction (MVO) is the underlying cause for the no-reflow
      phenomenon in ST-segment elevation myocardial infarction (STEMI). The association
      between MVO assessed by cardiac magnetic resonance imaging (CMR) and prognosis
      has not been convincingly demonstrated. We sought to determine the relationship
      between MVO assessed early after primary percutaneous coronary intervention (PCI)
      in STEMI and all-cause mortality, hospitalization for heart failure (HF), and
      reinfarction. Methods and results: We performed a pooled analysis using
      individual patient data from seven randomized primary PCI trials in which MVO was
      assessed within 7 days after reperfusion by CMR using late gadolinium enhancement
      imaging (n = 1688). Clinical follow-up was performed for at least 6 months after
      the index event. Median time to CMR after STEMI was 3 days [interquartile range
      (IQR) 2-4], and median duration of clinical follow-up was 365 days (IQR 188-374).
      Microvascular obstruction was present in 960 (56.9%) of patients, and median MVO
      (percent left ventricular myocardial mass) was 0.47% (IQR 0.00-2.54). A graded
      response was present between the extent of MVO (per 1.0% absolute increase) and
      subsequent mortality [Cox adjusted hazard ratio (HR) 1.14, 95% confidence
      interval (CI) 1.09-1.19, P < 0.0001] and hospitalization for HF (Cox adjusted HR
      1.08, 95% CI 1.05-1.12, P < 0.0001). Microvascular obstruction remained
      significantly associated with all-cause mortality even after further adjustment
      for infarct size (Cox adjusted HR 1.09, 95% CI 1.01-1.17, P = 0.03). MVO was not
      significantly related to subsequent reinfarction (P = 0.29). Conclusions: The
      presence and extent of MVO measured by CMR after primary PCI in STEMI are
      strongly associated with mortality and hospitalization for HF within 1 year.

PMID- 29020249
TI  - Increasing Evidence of the Nephrotoxicity of Piperacillin/Tazobactam and
      Vancomycin Combination Therapy-What Is the Clinician to Do?
AB  - Early administration of appropriate empiric antibiotics is essential for
      achieving the best possible outcomes in sepsis. Yet the choice of antibiotic
      therapy has become more challenging due to recent reports of nephrotoxicity with
      the combination of vancomycin and piperacillin/tazobactam, the "workhorse"
      regimen at many institutions. In this article we assess the evidence for
      nephrotoxicity and its possible mechanisms, provide recommendations for risk
      mitigation, address the advantages and disadvantages of alternative antibiotic
      choices, and suggest areas for future research.

PMID- 29020247
TI  - Assessment of Efficacy and Safety of Arterolane Maleate-Piperaquine Phosphate
      Dispersible Tablets in Comparison With Artemether-Lumefantrine Dispersible
      Tablets in Pediatric Patients With Acute Uncomplicated Plasmodium falciparum
      Malaria: A Phase 3, Randomized, Multicenter Trial in India and Africa.
AB  - Background: Administration of artemisinin-based combination therapy (ACT) to
      infant and young children can be challenging. A formulation with accurate dose
      and ease of administration will improve adherence and compliance in children. The
      fixed-dose combination dispersible tablet of arterolane maleate (AM) 37.5 mg and
      piperaquine phosphate (PQP) 187.5 mg can make dosing convenient in children.
      Methods: This multicenter (India and Africa), comparative, parallel-group trial
      enrolled 859 patients aged 6 months to 12 years with Plasmodium falciparum
      malaria. Patients were randomized in a ratio of 2:1 to AM-PQP (571 patients) once
      daily and artemether-lumefantrine (AL) (288 patients) twice daily for 3 days and
      followed for 42 days. Results: The cure rate (ie, polymerase chain reaction
      corrected adequate clinical and parasitological response) in the per-protocol
      population at day 28 was 100.0% and 98.5% (difference, 1.48% [95% confidence
      interval {CI}, .04%-2.91%]) in the AM-PQP and AL arms, respectively, and 96.0%
      and 95.8% (difference, 0.14% [95% CI, -2.68% to 2.95%]) in the intention-to-treat
      (ITT) population. The cure rate was comparable at day 42 in the ITT population
      (AM-PQP, 94.4% vs AL, 93.1%). The median parasite clearance time was 24 hours in
      both the arms. The median fever clearance time was 6 hours in AM-PQP and 12 hours
      in the AL arm. Both the treatments were found to be safe and well tolerated.
      Overall, safety profile of both the treatments was similar. Conclusions: The
      efficacy and safety of fixed-dose combination of AM and PQP was comparable to AL
      for the treatment of uncomplicated P. falciparum malaria in pediatric patients.
      Clinical Trials Registration: CTRI/2014/07/004764.

PMID- 29020252
TI  - Short-term Peripheral Venous Catheter-Related Bloodstream Infections: A
      Systematic Review.
AB  - Short-term peripheral venous catheters (PVCs) are commonly used in healthcare
      settings. To determine the magnitude of bloodstream infections (BSIs) related to
      their use, PubMed, article bibliographies, and the authors' library were searched
      for pertinent articles. The incidence of PVC-related BSIs was 0.18% among 85063
      PVCs. Short-term PVCs accounted for a mean of 6.3% and 23% of nosocomial BSIs and
      nosocomial catheter-related BSIs, respectively. Prolonged dwell time and catheter
      insertion under emergent conditions increased risk of PVC-related bloodstream
      infection (PVCR-BSI). If approximately 200 million PVCs are successfully inserted
      into adult patients each year in the United States, there may be many PVCR-BSIs
      occurring yearly. Clinicians should obtain blood cultures in patients with
      evidence of PVC infection and systemic symptomatology such as fever, carefully
      inspect the PVC insertion site in bacteremic or fungemic patients, and remove
      PVCs associated with localized infection with or without associated BSI.

PMID- 29020253
TI  - Aneurysmal left sinus of Valsalva in Marfan's syndrome.

PMID- 29020251
TI  - Differential blood pressure effects of ibuprofen, naproxen, and celecoxib in
      patients with arthritis: the PRECISION-ABPM (Prospective Randomized Evaluation of
      Celecoxib Integrated Safety Versus Ibuprofen or Naproxen Ambulatory Blood
      Pressure Measurement) Trial.
AB  - Aims: Non-steroidal anti-inflammatory drugs (NSAIDs), both non-selective and
      selective cyclooxygenase-2 (COX-2) inhibitors, are among the most widely
      prescribed drugs worldwide, but associate with increased blood pressure (BP) and
      adverse cardiovascular (CV) events. PRECISION-ABPM, a substudy of PRECISION was
      conducted at 60 sites, to determine BP effects of the selective COX-2 inhibitor
      celecoxib vs. the non-selective NSAIDs naproxen and ibuprofen. Methods and
      results: In this double-blind, randomized, multicentre non-inferiority CV-safety
      trial, 444 patients (mean age 62 +/- 10 years, 54% female) with osteoarthritis
      (92%) or rheumatoid arthritis (8%) and evidence of or at increased risk for
      coronary artery disease received celecoxib (100-200 mg bid), ibuprofen (600-800
      mg tid), or naproxen (375-500 mg bid) with matching placebos in a 1: 1: 1
      allocation, to assess the effect on 24-h ambulatory BP after 4 months. The change
      in mean 24-h systolic BP (SBP) in celecoxib, ibuprofen and naproxen-treated
      patients was -0.3 mmHg [95% confidence interval (CI), -2.25, 1.74], 3.7 (95% CI,
      1.72, 5.58) and 1.6 mmHg (95% CI, -0.40, 3.57), respectively. These changes
      resulted in a difference of - 3.9 mmHg (P = 0.0009) between celecoxib and
      ibuprofen, of - 1.8 mmHg (P = 0.12) between celecoxib and naproxen, and of - 2.1
      mmHg (P = 0.08) between naproxen and ibuprofen. The percentage of patients with
      normal baseline BP who developed hypertension (mean 24-h SBP >= 130 and/or
      diastolic BP >= 80 mmHg) was 23.2% for ibuprofen, 19.0% for naproxen, and 10.3%
      for celecoxib (odds ratio 0.39, P = 0.004 and odds ratio 0.49, P = 0.03 vs.
      ibuprofen and naproxen, respectively). Conclusions: In PRECISION-ABPM, allocation
      to the non-selective NSAID ibuprofen, compared with the COX-2 selective inhibitor
      celecoxib was associated with a significant increase of SBP, and a higher
      incidence of new-onset hypertension. ClinicalTrials: gov number NCT00346216.

PMID- 29020255
TI  - Mini-Fecal Microbiota Transplantation for Treatment of Clostridium difficile
      Proctitis Following Total Colectomy.
AB  - Rarely, in fulminant Clostridium difficile infection (CDI), the rectal stump is
      persistently infected following total abdominal colectomy. We report cure of a
      septic patient with proctitis by fecal microbiota transplant via rectal swabs
      (mini-FMT). This novel procedure offers a management option for recurrent CDI
      following total abdominal colectomy.

PMID- 29020254
TI  - Statistical Analysis of Multiple Phenotypes in Genetic Epidemiologic Studies:
      From Cross-Phenotype Associations to Pleiotropy.
AB  - In the context of genetics, pleiotropy refers to the phenomenon in which a single
      genetic locus affects more than 1 trait or disease. Genetic epidemiologic studies
      have identified loci associated with multiple phenotypes, and these cross
      phenotype associations are often incorrectly interpreted as examples of
      pleiotropy. Pleiotropy is only one possible explanation for cross-phenotype
      associations. Cross-phenotype associations may also arise due to issues related
      to study design, confounder bias, or nongenetic causal links between the
      phenotypes under analysis. Therefore, it is necessary to dissect cross-phenotype
      associations carefully to uncover true pleiotropic loci. In this review, we
      describe statistical methods that can be used to identify robust statistical
      evidence of pleiotropy. First, we provide an overview of univariate and
      multivariate methods for discovery of cross-phenotype associations and highlight
      important considerations for choosing among available methods. Then, we describe
      how to dissect cross-phenotype associations by using mediation analysis.
      Pleiotropic loci provide insights into the mechanistic underpinnings of disease
      comorbidity, and they may serve as novel targets for interventions that
      simultaneously treat multiple diseases. Discerning between different types of
      cross-phenotype associations is necessary to realize the public health potential
      of pleiotropic loci.

PMID- 29020250
TI  - Empiric Therapy With Carbapenem-Sparing Regimens for Bloodstream Infections due
      to Extended-Spectrum beta-Lactamase-Producing Enterobacteriaceae: Results From
      the INCREMENT Cohort.
AB  - Background: There is little information about the efficacy of active alternative
      drugs to carbapenems except beta-lactam/beta-lactamase inhibitors for the
      treatment of bloodstream infections (BSIs) due to extended-spectrum beta
      lactamase-producing Enterobacteriaceae (ESBL-E). The objective of this study was
      to assess the outcomes of patients with BSI due to ESBL-E who received empiric
      therapy with such drugs (other active drugs [OADs]) or carbapenems. Methods: A
      multinational retrospective cohort study of patients with BSI due to ESBL-E who
      received empiric treatment with OADs or carbapenems was performed. Cox regression
      including a propensity score for receiving OADs was performed to analyze 30-day
      all-cause mortality as main outcome. Clinical failure and length of stay were
      also analyzed. Results: Overall, 335 patients were included; 249 received empiric
      carbapenems and 86 OADs. The most frequent OADs were aminoglycosides (43
      patients) and fluoroquinolones (20 patients). Empiric therapy with OADs was not
      associated with mortality (hazard ratio [HR], 0.75; 95% confidence interval [CI],
      .38-1.48) in the Cox regression analysis. Propensity score-matched pairs,
      subgroups, and sensitivity analyses did not show different trends; specifically,
      the adjusted HR for aminoglycosides was 1.05 (95% CI, .51-2.16). OADs were
      neither associated with 14-day clinical failure (adjusted odds ratio, 0.62; 95%
      CI, .29-1.36) nor length of hospital stay. Conclusions: We were unable to show
      that empiric treatment with OAD was associated with a worse outcome compared with
      carbapenems. This information allows more options to be considered for empiric
      therapy, at least for some patients, depending on local susceptibility patterns
      of ESBL-E.

PMID- 29020256
TI  - When to Censor?
AB  - Loss to follow-up is an endemic feature of time-to-event analyses that precludes
      observation of the event of interest. To our knowledge, in typical cohort studies
      with encounters occurring at regular or irregular intervals, there is no
      consensus on how to handle person-time between participants' last study encounter
      and the point at which they meet a definition of loss to follow-up. We
      demonstrate, using simulation and an example, that when the event of interest is
      captured outside of a study encounter (e.g., in a registry), person-time should
      be censored when the study-defined criterion for loss to follow-up is met (e.g.,
      1 year after last encounter), rather than at the last study encounter.
      Conversely, when the event of interest must be measured within the context of a
      study encounter (e.g., a biomarker value), person-time should be censored at the
      last study encounter. An inappropriate censoring scheme has the potential to
      result in substantial bias that may not be easily corrected.

PMID- 29020258
TI  - Reply to Gupta-Wright et al.

PMID- 29020257
TI  - Reappraising myocardial fibrosis in severe aortic stenosis: an invasive and non
      invasive study in 133 patients.
AB  - Aims: To investigate myocardial fibrosis (MF) in a large series of severe aortic
      stenosis (AS) patients using invasive biopsy and non-invasive imaging. Methods
      and results: One hundred thirty-three patients with severe, symptomatic AS
      accepted for surgical aortic valve replacement underwent cardiovascular magnetic
      resonance (CMR) with late gadolinium enhancement (LGE) and extracellular volume
      fraction (ECV) quantification. Intra-operative left ventricular (LV) biopsies
      were performed by needle or scalpel, yielding tissue with (n = 53) and without
      endocardium (n = 80), and compared with 10 controls. Myocardial fibrosis occurred
      in three patterns: (i) thickened endocardium with a fibrotic layer; (ii)
      microscopic scars, with a subendomyocardial predominance; and (iii) diffuse
      interstitial fibrosis. Collagen volume fraction (CVF) was elevated (P < 0.001)
      compared with controls, and higher (P < 0.001) in endocardium-containing samples
      with a decreasing CVF gradient from the subendocardium (P = 0.001). Late
      gadolinium enhancement correlated with CVF (P < 0.001) but not ECV. Both LGE and
      ECV correlated independently (P < 0.001) with N-terminal pro-brain natriuretic
      peptide and high-sensitivity-troponin T. High ECV was also associated with worse
      LV remodelling, left ventricular ejection fraction and functional capacity.
      Combining high ECV and LGE better identified patients with more adverse LV
      remodelling, blood biomarkers and histological parameters, and worse functional
      capacity than each parameter alone. Conclusion: Myocardial fibrosis in severe AS
      is complex, but three main patterns exist: endocardial fibrosis, microscars
      (mainly in the subendomyocardium), and diffuse interstitial fibrosis. Neither
      histological CVF nor the CMR parameters ECV and LGE capture fibrosis in its
      totality. A combined, multi-parametric approach with ECV and LGE allows best
      stratification of AS patients according to the response of the myocardial
      collagen matrix.

PMID- 29020259
TI  - Report of an ESC-EAPCI Task Force on the evaluation and use of bioresorbable
      scaffolds for percutaneous coronary intervention: executive summary.
AB  - A previous Task Force of the European Society of Cardiology (ESC) and European
      Association of Percutaneous Cardiovascular Interventions (EAPCI) provided a
      report on recommendations for the non-clinical and clinical evaluation of
      coronary stents. Following dialogue with the European Commission, the Task Force
      was asked to prepare an additional report on the class of devices known as
      bioresorbable scaffolds (BRS). Five BRS have CE-mark approval for use in Europe.
      Only one device-the Absorb bioresorbable vascular scaffold-has published
      randomized clinical trial data and this data show inferior outcomes to
      conventional drug-eluting stents (DES) at 2-3 years. For this reason, at present
      BRS should not be preferred to conventional DES in clinical practice. The Task
      Force recommends that new BRS devices should undergo systematic non-clinical
      testing according to standardized criteria prior to evaluation in clinical
      studies. A clinical evaluation plan should include data from a medium sized,
      randomized trial against DES powered for a surrogate end point of clinical
      efficacy. Manufacturers of successful devices receive CE-mark approval for use
      and must have an approved plan for a large-scale randomized clinical trial with
      planned long-term follow-up.

PMID- 29020261
TI  - Aortic valve replacement in younger patients.

PMID- 29020260
TI  - Clinical implications of three-vessel fractional flow reserve measurement in
      patients with coronary artery disease.
AB  - Aims: There are limited data on the clinical implications of total physiologic
      atherosclerotic burden assessed by invasive physiologic studies in patients with
      coronary artery disease. We investigated the prognostic implications of total
      physiologic atherosclerotic burden assessed by total sum of fractional flow
      reserve (FFR) in three vessels (3V-FFR). Methods and results: A total of 1136
      patients underwent FFR measurement in three vessels (3V FFR-FRIENDS study,
      NCT01621438). The patients were classified into high and low 3V-FFR groups
      according to the median value of 3V-FFR (2.72). The primary endpoint was major
      adverse cardiac events (MACE, a composite of cardiac death, myocardial infarction
      and ischaemia-driven revascularization) at 2 years. Mean angiographic percent
      diameter stenosis and FFR were 43.7 +/- 19.3% and 0.90 +/- 0.08, respectively.
      There was a negative correlation between 3V-FFR and estimated 2-year MACE rate (P
      < 0.001). The patients in low 3V-FFR group showed a higher risk of 2-year MACE
      than those in the high 3V-FFR group [(7.1% vs. 3.8%, hazard ratio (HR) 2.205, 95%
      confidence interval (CI) 1.201-4.048, P = 0.011]. The higher 2-year MACE rate was
      mainly driven by the higher rate of ischaemia-driven revascularization in the low
      3V-FFR group (6.2% vs. 2.7%, HR 2.568, 95% CI 1.283-5.140, P = 0.008). In a
      multivariable adjusted model, low 3V-FFR was an independent predictor of MACE (HR
      2.031, 95% CI 1.078-3.830, P = 0.029). Conclusion: Patients with high total
      physiologic atherosclerotic burden assessed by 3V-FFR showed higher risk of 2
      year clinical events than those with low total physiologic atherosclerotic
      burden. The difference was mainly driven by ischaemia-driven revascularization
      for both functionally significant and insignificant lesions at baseline. Three
      vessel FFR might be used as a prognostic indicator in patients with coronary
      artery disease. Clinical trial registration: 3V FFR-FRIENDS study
      (https://clinicaltrials.gov/ct2/show/NCT01621438, NCT01621438).

PMID- 29020262
TI  - Cigarette Smoking and Risk of Early Natural Menopause.
AB  - Menopause before 45 years of age affects roughly 5%-10% of women and is
      associated with a higher risk of adverse health conditions. Although smoking may
      increase the risk of early menopause, evidence is inconsistent, and data
      regarding smoking amount, duration, cessation, associated risks, and patterns
      over time are scant. We analyzed data of 116,429 nurses from the Nurses' Health
      Study II from 1989 through 2011 and used Cox proportional hazards models to
      estimate hazard ratios adjusted for confounders. Compared with never-smokers,
      current smokers (hazard ratio (HR) = 1.90, 95% confidence interval (CI): 1.71,
      2.11) and former smokers (HR = 1.10, 95% CI: 1.00, 1.21) showed an increased risk
      of early menopause. Increased risks were observed among women who reported
      current smoking for 11-15 pack-years (HR = 1.72, 95% CI: 1.36, 2.18), 16-20 pack
      years (HR = 1.72, 95% CI: 1.38, 2.14), and more than 20 pack-years (HR = 2.42,
      95% CI: 2.11, 2.77). Elevated risk was observed in former smokers who reported 11
      15 pack-years (HR = 1.29, 95% CI: 1.07, 1.55), 16-20 pack-years (HR = 1.42, 95%
      CI: 1.13, 1.79), or more than 20 pack-years (HR = 1.54, 95% CI: 1.23, 1.93).
      Women who smoked 10 or fewer cigarettes/day but quit by age 25 had comparable
      risk to never-smokers (HR = 1.03, 95% CI: 0.91, 1.17). A dose-response
      relationship between smoking and early natural menopause risk, as well as reduced
      risk among quitters, may provide insights into the mechanisms of cigarette
      smoking in reproductive health.

PMID- 29020264
TI  - Examining the Association Between Apparent Temperature and Mental Health-Related
      Emergency Room Visits in California.
AB  - The association between ambient temperature and morbidity has been explored
      previously. However, the association between temperature and mental health
      related outcomes, including violence and self-harm, remains relatively
      unexamined. For the period 2005-2013, we obtained daily counts of mental health
      related emergency room visits involving injuries with an external cause for 16
      California climate zones from the California Office of Statewide Health Planning
      and Development and combined them with data on mean apparent temperature, a
      combination of temperature and humidity. Using Poisson regression models, we
      estimated climate zone-level associations and then used random-effects meta
      analyses to produce overall estimates. Analyses were stratified by season (warm:
      May-October; cold: November-April), race/ethnicity, and age. During the warm
      season, a 10 degrees F (5.6 degrees C) increase in same-day mean apparent
      temperature was associated with 4.8% (95% confidence interval (CI): 3.6, 6.0),
      5.8% (95% CI: 4.5, 7.1), and 7.9% (95% CI: 7.3, 8.4) increases in the risk of
      emergency room visits for mental health disorders, self-injury/suicide, and
      intentional injury/homicide, respectively. High temperatures during the cold
      season were also positively associated with these outcomes. Variations were
      observed by race/ethnicity, age group, and sex, with Hispanics, whites, persons
      aged 6-18 years, and females being at greatest risk for most outcomes. Increasing
      mean apparent temperature was found to have acute associations with mental health
      outcomes and intentional injuries, and these findings warrant further study in
      other locations.

PMID- 29020265
TI  - Looking at the Force beyond the Dark side of mechanical massage.

PMID- 29020266
TI  - Propionibacterium avidum: A Virulent Pathogen Causing Hip Periprosthetic Joint
      Infection.
AB  - Background: Propionibacteria are important members of the human skin microbiota,
      but are also opportunistic pathogens associated with periprosthetic joint
      infection (PJI). While the role of Propionibacterium acnes in PJI has been widely
      described, insight into the capacity of Propionibacterium avidum to cause PJI is
      limited. Methods: An unusual cluster of 4 hip PJIs caused by P. avidum in one
      orthopedic center in 2015 prompted us to retrospectively identify and analyze
      clinical data related to previous P. avidum PJI cases (1997-2015). We also
      characterized the hemolytic and biofilm-producing capacity of our 4 clinical P.
      avidum strains isolated in 2015, and investigated their phylogenetic
      relationships by whole-genome sequencing. Results: We retrospectively identified
      13 P. avidum PJIs, with the majority being hip-related infections (n = 11).
      Preoperative synovial fluid cultures were P. avidum positive in 63.6% of cases.
      Six of 12 patients (50%) with available case histories were treated with an
      exchange of the prosthesis. In all but 1 of the 6 patients treated with
      debridement-retention of the prosthesis, treatment failed, thus requiring a 2
      stage revision. The isolated P. avidum strains showed a more pronounced hemolytic
      activity, but a similar biofilm-forming ability when compared to P. acnes. Whole
      genome sequencing identified 2 phylogenetic clusters highly related to P. avidum
      PJI strains isolated in Sweden. Conclusions: We describe the largest series of P.
      avidum PJI predominantly located in the hip. Phylogenetic similarity of our P.
      avidum strains to PJI strains isolated elsewhere suggests that these invasive
      lineages may be common.

PMID- 29020269
TI  - Hepatitis C Screening: From Modeling to Public Health Policy.

PMID- 29020268
TI  - Office blood pressure or ambulatory blood pressure for the prediction of
      cardiovascular events.
AB  - Aims: To determine the added value of (i) 24-h ambulatory blood pressure relative
      to office blood pressure and (ii) night-time ambulatory blood pressure relative
      to daytime ambulatory blood pressure for 10-year person-specific absolute risks
      of fatal and non-fatal cardiovascular events. Methods and results: A total of
      7927 participants were included from the International Database on Ambulatory
      blood pressure monitoring in relation to Cardiovascular Outcomes. We used cause
      specific Cox regression to predict 10-year person-specific absolute risks of
      fatal and non-fatal cardiovascular events. Discrimination of 10-year outcomes was
      assessed by time-dependent area under the receiver operating characteristic curve
      (AUC). No differences in predicted risks were observed when comparing office
      blood pressure and ambulatory blood pressure. The median difference in 10-year
      risks (1st; 3rd quartile) was -0.01% (-0.3%; 0.1%) for cardiovascular mortality
      and -0.1% (-1.1%; 0.5%) for cardiovascular events. The difference in AUC (95%
      confidence interval) was 0.65% (0.22-1.08%) for cardiovascular mortality and
      1.33% (0.83-1.84%) for cardiovascular events. Comparing daytime and night-time
      blood pressure, the median difference in 10-year risks was 0.002% (-0.1%; 0.1%)
      for cardiovascular mortality and -0.01% (-0.5%; 0.2%) for cardiovascular events.
      The difference in AUC was 0.10% (-0.08 to 0.29%) for cardiovascular mortality and
      0.15% (-0.06 to 0.35%) for cardiovascular events. Conclusion: Ten-year
      predictions obtained from ambulatory blood pressure are similar to predictions
      from office blood pressure. Night-time blood pressure does not improve 10-year
      predictions obtained from daytime measurements. For an otherwise healthy
      population sufficient prognostic accuracy of cardiovascular risks can be achieved
      with office blood pressure.

PMID- 29020270
TI  - Homozygous familial hypercholesterolaemia: light at the end of the tunnel.

PMID- 29020271
TI  - Renal denervation: will the Phoenix rise from the ashes?

PMID- 29020267
TI  - Burden of Influenza in 4 Ecologically Distinct Regions of Peru: Household Active
      Surveillance of a Community Cohort, 2009-2015.
AB  - Background: There are limited data on the burden of disease posed by influenza in
      low- and middle-income countries. Furthermore, most estimates of influenza
      disease burden worldwide rely on passive sentinel surveillance at health clinics
      and hospitals that lack accurate population denominators. Methods: We documented
      influenza incidence, seasonality, health-system utilization with influenza
      illness, and vaccination coverage through active community-based surveillance in
      4 ecologically distinct regions of Peru over 6 years. Approximately 7200 people
      in 1500 randomly selected households were visited 3 times per week. Naso- and
      oropharyngeal swabs were collected from persons with influenza-like illness and
      tested for influenza virus by real-time reverse-transcription polymerase chain
      reaction. Results: We followed participants for 35353 person-years (PY). The
      overall incidence of influenza was 100 per 1000 PY (95% confidence interval [CI],
      97-104) and was highest in children aged 2-4 years (256/1000 PY [95% CI, 236
      277]). Seasonal incidence trends were similar across sites, with 61% of annual
      influenza cases occurring during the austral winter (May-September). Of all
      participants, 44 per 1000 PY (95% CI, 42-46) sought medical care, 0.7 per 1000 PY
      (95% CI, 0.4-1.0) were hospitalized, and 1 person died (2.8/100000 PY). Influenza
      vaccine coverage was 27% among children aged 6-23 months and 26% among persons
      aged >=65 years. Conclusions: Our results indicate that 1 in 10 persons develops
      influenza each year in Peru, with the highest incidence in young children. Active
      community-based surveillance allows for a better understanding of the true burden
      and seasonality of disease that is essential to plan the optimal target groups,
      timing, and cost of national influenza vaccination programs.

PMID- 29020272
TI  - Walking pace and handgrip strength: simple measures of fitness and mortality
      risk?

PMID- 29020274
TI  - The Times They Are A-Changin': Time-Dependent Exposures and Time-Dependent
      Confounders.

PMID- 29020273
TI  - The Transmissibility of Antibiotic-Resistant Enterobacteriaceae in Intensive Care
      Units.
AB  - Background: The global emergence of infections caused by Enterobacteriaceae
      resistant to expanded-spectrum cephalosporins (ESCs) in intensive care units
      (ICUs) is, at least partly, driven by cross-transmission. Yet, individual
      transmission capacities of bacterial species have not been quantified. Methods:
      In this post hoc analysis of a multicenter study in 13 European ICUs, prospective
      surveillance data and a mathematical model were used to estimate transmission
      capacities and single-admission reproduction numbers (RA) of Escherichia coli and
      non-E. coli Enterobacteriaceae (non-EcE), all being ESC resistant. Surveillance
      was based on a chromogenic selective medium for ESC-resistant Enterobacteriaceae,
      allowing identification of E. coli and of Klebsiella, Enterobacter, Serratia, and
      Citrobacter species, grouped as non-EcE. Results: Among 11420 patients included,
      the admission prevalence was 3.8% for non-EcE (74% being Klebsiella pneumoniae)
      and 3.3% for E. coli. Acquisition rates were 7.4 and 2.6 per 100 admissions at
      risk for non-EcE and E. coli, respectively. The estimated transmission capacity
      of non-EcE was 3.7 (95% credibility interval [CrI], 1.4-11.3) times higher than
      that of E. coli, yielding single-admission reproduction numbers (RA) of 0.17 (95%
      CrI, .094-.29) for non-EcE and 0.047 (95% CrI, .018-.098) for E. coli.
      Conclusions: In ICUs, non-EcE, mainly K. pneumoniae, are 3.7 times more
      transmissible than E. coli. Estimated RA values of these bacteria were below the
      critical threshold of 1, suggesting that in these ICUs outbreaks typically remain
      small with current infection control policies.

PMID- 29020263
TI  - 2017 HIVMA of IDSA Clinical Practice Guideline for the Management of Chronic Pain
      in Patients Living With HIV.
AB  - Pain has always been an important part of human immunodeficiency virus (HIV)
      disease and its experience for patients. In this guideline, we review the types
      of chronic pain commonly seen among persons living with HIV (PLWH) and review the
      limited evidence base for treatment of chronic noncancer pain in this population.
      We also review the management of chronic pain in special populations of PLWH,
      including persons with substance use and mental health disorders. Finally, a
      general review of possible pharmacokinetic interactions is included to assist the
      HIV clinician in the treatment of chronic pain in this population.It is important
      to realize that guidelines cannot always account for individual variation among
      patients. They are not intended to supplant physician judgment with respect to
      particular patients or special clinical situations. The Infectious Diseases
      Society of American considers adherence to these guidelines to be voluntary, with
      the ultimate determination regarding their application to be made by the
      physician in the light of each patient's individual circumstances.

PMID- 29020275
TI  - Citius, Altius, Fortius: The New Paradigm in the Treatment of Chronic Hepatitis C
      Disease.
AB  - With the advent of the direct-acting antiviral agents (DAAs) for chronic
      hepatitis C infection, the treatment paradigm has dramatically changed,
      especially the duration, tolerability, and response to therapy. The DAAs fall
      into several classes and are variously indicated in the treatment of one or more
      genotypes of infection. All these agents are orally administered and, as they are
      largely renally eliminated (with exceptions), do not require adjustment in mild
      to moderate renal insufficiency. Most of these agents demonstrate a high barrier
      to resistance and are extremely well-tolerated by patients. Overall efficacy
      rates are >=90%.

PMID- 29020276
TI  - Antibiotic Expenditures by Medication, Class, and Healthcare Setting in the
      United States, 2010-2015.
AB  - Background: Improving antibiotic use has the potential to decrease healthcare
      costs by reducing the incidence of antibiotic-resistant infections, antibiotic
      associated adverse events, and expenditures due to unnecessary prescriptions.
      Antibiotic expenditures in 2009 totaled $10.7 billion in the United States. Since
      then, national and local antibiotic stewardship initiatives have grown. The
      purpose of this study was to assess trends in antibiotic expenditures by
      healthcare setting in the United States between 2010 and 2015. Methods: Systemic
      (nontopical) antibiotic expenditures from January 2010 to December 2015 were
      extracted from the QuintilesIMS National Sales Perspectives database. These data
      represent a statistically valid projection of US medication purchases. Regression
      analyses evaluated trends in expenditures over the study period. Results:
      Antibiotic expenditures totaled $56.0 billion over the 6-year period; the
      majority (59.1%) of expenditures were associated with the outpatient setting.
      Overall antibiotic expenditures in 2015 ($8.8 billion) were 16.6% lower than in
      2010 ($10.6 billion). Antibiotic expenditures similarly decreased in the
      community by 25.5% (P = .05), but outpatient clinics and mail service pharmacy
      expenditures experienced significant growth (148% and 67% increase, respectively;
      P < .01 for both). In 2015, 16.5% of antibiotic expenditures in the community
      were for parenteral formulations, an increase of 25%. Conclusions: From 2010 to
      2015, antibiotic expenditures decreased. The majority of antibiotic expenditures
      were in the outpatient setting, specifically community pharmacies. Expenditures
      for intravenous agents in the community are increasing and may represent
      increased use. These results reinforce the importance of antibiotic stewardship
      efforts across the spectrum of healthcare.

PMID- 29020277
TI  - HIV-care access among people with incarceration experience in St. Petersburg,
      Russia.
AB  - Background: Little is known about the clinical care experiences of HIV-infected
      persons in St. Petersburg who have experience with incarceration. To address this
      question, we conducted a capture-recapture study to identify individuals who had
      been diagnosed with HIV infection while incarcerated and who subsequently
      presented for medical care in St. Petersburg, Russia following release from
      prison. Methods: We matched 292 HIV-positive prisoners tested by the prison
      system in 2010 to the medical records at the St. Petersburg AIDS Center in the
      following 4 years. Results: The data analysis shows that as many as half of HIV+
      prisoners fail to seek treatment in the community upon release. Of those who had
      sought care post-release, only 36% were receiving HAART. Of the 109 individuals
      for whom tuberculosis testing was indicated post-release, 36.7% were found to be
      reactive. Conclusion: Despite the limitations of the data, this study is the
      first of its kind to review records documenting HIV care among prisoners in
      Russia post-incarceration. In addition to providing important descriptive
      information about this marginalized population, the findings from this study
      highlight areas where HIV control efforts could be improved in order to address
      the HIV epidemic in the Russian Federation.

PMID- 29020278
TI  - Depressive Symptoms in Patients Referred to a Tertiary Lyme Center: High
      Prevalence in Those Without Evidence of Lyme Borreliosis.
AB  - Background: Controversy exists whether mood disorders, such as depression, are
      associated with Lyme borreliosis (LB). The study objective was to assess
      prevalence of depressive symptoms in subgroups of patients referred to a tertiary
      Lyme center, to investigate whether depressive symptoms can be used in clinical
      practice to discriminate for LB. Methods: This cohort study included adult
      patients who visited a tertiary Lyme center between January 2008 and December
      2014. Prior to medical consultation, serum samples were taken and the Beck
      Depression Inventory II was completed to assess depressive symptoms. Lyme
      diagnosis was retrospectively extracted from the patient's medical record.
      Patients were classified based on clinical LB and serology results. Prevalence of
      moderate/severe depressive symptoms was calculated. Using logistic regression,
      odds ratios with 95% confidence intervals (CIs) were calculated for
      moderate/severe depressive symptoms. Results: In total, 1454 patients were
      included. Prevalence of moderate/severe depressive symptoms was lowest in
      patients with no clinical LB and positive serology (15.3%), higher in patients
      with clinical LB with positive and negative serology (19.3% and 20.9%
      respectively), and highest in patients with no clinical LB and negative serology
      (29.3%). The odds ratio for moderate/severe depressive symptoms in patients with
      LB and positive serology was 0.71 (95% CI, .50-1.03) compared to patients with no
      LB and negative serology. Conclusions: The prevalence of depressive symptoms was
      similar in patients with LB compared to patients with no evidence of infection.
      This suggests that depressive symptoms cannot be used to discriminate for LB in a
      tertiary Lyme center.

PMID- 29020279
TI  - Cost Drivers of a Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated
      Bacterial Pneumonia Phase 3 Clinical Trial.
AB  - Background: Studies indicate that the prevalence of multidrug-resistant
      infections, including hospital-acquired bacterial pneumonia and ventilator
      associated bacterial pneumonia (HABP/VABP), has been rising. There are many
      challenges associated with these disease conditions and the ability to develop
      new treatments. Additionally, HABP/VABP clinical trials are very costly to
      conduct given their complex protocol designs and the difficulty in recruiting and
      retaining patients. Methods: With input from clinicians, representatives from
      industry, and the US Food and Drug Administration, we conducted a study to (1)
      evaluate the drivers of HABP/VABP phase 3 direct and indirect clinical trial
      costs; (2) to identify opportunities to lower these costs; and (3) to compare (1)
      and (2) to endocrine and oncology clinical trials. Benchmark data were gathered
      from proprietary and commercial databases and used to create a model that
      calculates the fully loaded (direct and indirect) cost of typical phase 3
      HABP/VABP endocrine and oncology clinical trials. Results: Results indicate that
      the cost per patient for a 200-site, 1000-patient phase 3 HABP/VABP study is
      $89600 per patient. The cost of screen failures and screen failure rates are the
      main cost drivers. Conclusions: Results indicate that biopharmaceutical companies
      and regulatory agencies should consider strategies to improve screening and
      recruitment to decrease HABP/VABP clinical trial costs.

PMID- 29020280
TI  - Campylobacter fetus Cluster Among Men Who Have Sex With Men, Montreal, Quebec,
      Canada, 2014-2016.
AB  - From March 2014 to December 2016, a cluster of 13 cases of Campylobacter fetus
      intestinal and extraintestinal infections, including 2 patients with an aortic
      mycotic aneurysm, caused significant morbidity. The cluster likely resulted from
      sexual transmission between men having sex with men living in the greater
      Montreal area, Quebec, Canada.

PMID- 29020281
TI  - Association of walking pace and handgrip strength with all-cause, cardiovascular,
      and cancer mortality: a UK Biobank observational study.
AB  - Aims: To quantify the association of self-reported walking pace and handgrip
      strength with all-cause, cardiovascular, and cancer mortality. Methods and
      results: A total of 230 670 women and 190 057 men free from prevalent cancer and
      cardiovascular disease were included from UK Biobank. Usual walking pace was self
      defined as slow, steady/average or brisk. Handgrip strength was assessed by
      dynamometer. Cox-proportional hazard models were adjusted for social deprivation,
      ethnicity, employment, medications, alcohol use, diet, physical activity, and
      television viewing time. Interaction terms investigated whether age, body mass
      index (BMI), and smoking status modified associations. Over 6.3 years, there were
      8598 deaths, 1654 from cardiovascular disease and 4850 from cancer. Associations
      of walking pace with mortality were modified by BMI. In women, the hazard ratio
      (HR) for all-cause mortality in slow compared with fast walkers were 2.16 [95%
      confidence interval (CI): 1.68-2.77] and 1.31 (1.08-1.60) in the bottom and top
      BMI tertiles, respectively; corresponding HRs for men were 2.01 (1.68-2.41) and
      1.41 (1.20-1.66). Hazard ratios for cardiovascular mortality remained above 1.7
      across all categories of BMI in men and women, with modest heterogeneity in men.
      Handgrip strength was associated with cardiovascular mortality in men only (HR
      tertile 1 vs. tertile 3 = 1.38; 1.18-1.62), without differences across BMI
      categories, while associations with all-cause mortality were only seen in men
      with low BMI. Associations for walking pace and handgrip strength with cancer
      mortality were less consistent. Conclusion: A simple self-reported measure of
      slow walking pace could aid risk stratification for all-cause and cardiovascular
      mortality within the general population.

PMID- 29020283
TI  - Retrospective cohort study of breast cancer incidence, health service use and
      outcomes in Europe: a study of feasibility.
AB  - Background: Comparisons of outcomes of health care in different systems can be
      used to inform health policy. The EuroHOPE (European Healthcare Outcomes,
      Performance and Efficiency) project investigated the feasibility of comparing
      routine data on selected conditions including breast cancer across participating
      European countries. Methods: Routine data on incidence, treatment and mortality
      by age and clinical characteristics for breast cancer in women over 24 years of
      age were obtained (for a calendar year) from linked hospital discharge records,
      cancer and death registers from Finland, the Turin metropolitan area, Scotland
      and Sweden (all 2005), Hungary (2006) and Norway (2009). Age-adjusted breast
      cancer incidence and 1-year survival were estimated for each country/region.
      Results: In total, 24 576 invasive breast cancer cases were identified from
      cancer registries from over 13 million women. Age-adjusted incidence ranged from
      151.1 (95%CI 147.2-155.0) in Hungary to 234.7 (95%CI 227.4-242.0)/100 000 in
      Scotland. One-year survival ranged from 94.1% (95%CI 93.5-94.7%) in Scotland to
      97.1% (95%CI 96.2-98.1%) in Italy. Scotland had the highest proportions of poor
      prognostic factors in terms of tumour size, nodal status and metastases.
      Significant variations in data completeness for prognostic factors prevented
      adjustment for case mix. Conclusion: Incidence of and survival from breast cancer
      showed large differences between countries. Substantial improvements in the use
      of internationally recognised common terminology, standardised data coding and
      data completeness for prognostic indicators are required before international
      comparisons of routine data can be used to inform health policy.

PMID- 29020282
TI  - Elevated Levels of Estradiol in Human Immunodeficiency Virus-Infected Pregnant
      Women on Protease Inhibitor-Based Regimens.
AB  - Background: Human immunodeficiency virus (HIV)-infected pregnant women on
      protease inhibitor (PI)-based combination antiretroviral therapy (cART) have a
      greater risk for adverse birth outcomes, and an association with steroid hormone
      levels has been implicated. The objective of this study was to investigate the
      association between PI-cART and estradiol levels in pregnancy. Methods: Fifty
      five HIV-infected and 49 HIV-uninfected Canadian pregnant women were followed
      prospectively throughout gestation. All HIV-infected women were on a PI-based
      cART regimen. Maternal plasma samples were collected at 12-18 weeks, 24-28 weeks,
      34-38 weeks, at delivery, and from the cord. Birth outcomes were recorded. Levels
      of estradiol, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding
      globulin (SHBG), cortisol, and adrenocorticotropic hormone (ACTH) were quantified
      by enzyme-linked immunosorbent assay. Results: (median [interquartile range] for
      cord estradiol: 23.9 ng/mL [16.4-36.4] for HIV-infected exposed to PI-cART and
      15.7 ng/mL [12.2-21.2] for HIV-negative; P = .0025). HIV-infected women had
      higher DHEAS levels in cord plasma that correlated with cord and maternal
      delivery estradiol levels. Cortisol and ACTH levels did not differ between
      groups. In the HIV-infected women, cord estradiol levels correlated negatively
      with birth weight centile (r = -0.47, P = .0016). Conclusions: Our data suggest
      that PI-cART exposure in pregnancy is associated with elevated levels of
      estradiol, likely driven by higher fetal DHEAS production. Cord estradiol levels
      were inversely correlated with birth weight centile in infants born to PI-cART
      exposed women, suggesting that fetal exposure to high estradiol levels may be
      contributing to cART-associated fetal growth restriction.

PMID- 29020284
TI  - Performance of Targeted Fungal Sequencing for Culture-Independent Diagnosis of
      Invasive Fungal Disease.
AB  - Background: Identification of fungi causing invasive fungal disease (IFD) is
      critical for guiding antifungal therapy. We describe the performance and clinical
      impact of a targeted panfungal polymerase chain reaction (PCR) amplicon
      sequencing assay for culture-independent diagnosis of IFD. Methods: Between
      January 2009 and September 2016, 233 specimens, consisting of fresh and formalin
      fixed, paraffin-embedded (FFPE) tissues and sterile body fluids with known
      diagnosis of IFD based on reference method results (n = 117), and specimens with
      negative fungal culture, but with microscopic and ancillary findings indicative
      of IFD (n = 116), were included. PCR amplicons from the internal transcribed
      spacer 2 and the D2 region of 28S ribosomal RNA gene were sequenced and fungi
      identified. Results: Sensitivity and specificity of fungal sequencing in
      specimens with known diagnosis were 96.6% (95% confidence interval [CI], 87.4%
      99.4%; 58/60) and 98.2% (95% CI, 89.4%-99.9%; 56/57). In patients with suspected
      IFD, the diagnostic yield of fungal sequencing was 62.9% (73/116) overall and
      71.3% (57/80) in patients classified with proven IFD based on the European
      Organization for Research and Treatment of Cancer/Invasive Fungal Infections
      Cooperative Group and Mycoses Study Group (EORTC/MSG) criteria. Samples obtained
      by open biopsy had a significantly higher diagnostic yield (71.5% [40/56])
      compared with core-needle biopsy (50% [17/34] P = .04) and fine needle aspiration
      (0% [0/2]; P = .009). Additionally, D2 sequencing diagnosed 5 cases of invasive
      protozoal infections due to Toxoplasma gondii (n = 3), Trypanosoma cruzi, and
      Leishmania species. Sequencing results altered patient management in the majority
      of suspected cases. Conclusions: The targeted fungal sequencing assay allowed
      accurate identification of fungi causing IFD and additionally provided partial
      protozoal coverage. The diagnostic yield was dependent on the amount of tissue
      available for testing.

PMID- 29020285
TI  - Impact of Systemic Antibiotics on Staphylococcus aureus Colonization and
      Recurrent Skin Infection.
AB  - Background: Staphylococcus aureus colonization poses risk for subsequent skin and
      soft tissue infection (SSTI). We hypothesized that including systemic antibiotics
      in the management of S. aureus SSTI, in conjunction with incision and drainage,
      would reduce S. aureus colonization and incidence of recurrent infection.
      Methods: We prospectively evaluated 383 children with S. aureus SSTI requiring
      incision and drainage and S. aureus colonization in the anterior nares, axillae,
      or inguinal folds at baseline screening. Systemic antibiotic prescribing at the
      point of care was recorded. Repeat colonization sampling was performed within 3
      months (median, 38 days; interquartile range, 22-50 days) in 357 participants.
      Incidence of recurrent infection was ascertained for up to 1 year. Results:
      Participants prescribed guideline-recommended empiric antibiotics for purulent
      SSTI were less likely to remain colonized at follow-up sampling (adjusted hazard
      ratio [aHR], 0.49; 95% confidence interval [CI], .30-.79) and less likely to have
      recurrent SSTI (aHR, 0.57; 95% CI, .34-.94) than those not receiving guideline
      recommended empiric antibiotics for their SSTI. Additionally, participants
      remaining colonized at repeat sampling were more likely to report a recurrent
      infection over 12 months (aHR, 2.37; 95% CI, 1.69-3.31). Clindamycin was more
      effective than trimethoprim-sulfamethoxazole (TMP-SMX) in eradicating S. aureus
      colonization (44% vs 57% remained colonized, P = .03) and preventing recurrent
      SSTI (31% vs 47% experienced recurrence, P = .008). Conclusions: Systemic
      antibiotics, as part of acute SSTI management, impact S. aureus colonization,
      contributing to a decreased incidence of recurrent SSTI. The mechanism by which
      clindamycin differentially affects colonization and recurrent SSTI compared to
      TMP-SMX warrants further study.

PMID- 29020287
TI  - Optical coherence tomography or intravascular ultrasound to optimize coronary
      stent implantation.

PMID- 29020288
TI  - Safety of non-steroidal anti-inflammatory drugs.

PMID- 29020289
TI  - A Novel Human Pegivirus, HPgV-2 (HHpgV-1), Is Tightly Associated With Hepatitis C
      Virus (HCV) Infection and HCV/Human Immunodeficiency Virus Type 1 Coinfection.
AB  - Background: Human pegivirus type 2 (HPgV-2) is a novel blood-borne human
      pegivirus that mainly infects hepatitis C virus (HCV)-infected subjects. We have
      investigated the prevalence of HPgV-2 in China, its association with HCV and
      human immunodeficiency virus type 1 (HIV-1), and the impact on HCV viral load and
      liver damage. Methods: A cross-sectional study was conducted with both blood
      donors and HCV- and HIV-1-infected patients in Guangzhou, China. All subjects
      were screened for anti-HPgV-2 and HPgV-2 RNA. Demographic and clinical
      information were obtained from electronic medical records. Results: We tested
      8198 serum or plasma samples. Only 0.15% (6/4017) of healthy blood donors were
      positive for anti-HPgV-2 and negative for HPgV-2 RNA. No HPgV-2 viremia was
      detected in hepatitis B virus- or HIV-1-monoinfected individuals. The relatively
      high frequency of HPgV-2 infection was observed in 1.23% (30/2440) and 0.29%
      (7/2440) of HCV-infected persons by serological assay and reverse-transcription
      polymerase chain reaction, respectively. Furthermore, anti-HPgV-2 and HPgV-2 RNA
      were detected in 8.91% (18/202) and 3.47% (7/202), respectively, of HCV/HIV-1
      coinfected subjects. HPgV-2 persistent infection was documented in about 30% of
      anti-HPgV-2-positive individuals. In addition, HPgV-2 infection may not affect
      HCV-related liver injury and HCV viral load. Conclusions: Our results indicate
      the rarity of HPgV-2 infection in the general population and tight association
      with HCV, in particular with HCV/HIV-1 coinfection. HPgV-2 appears not to worsen
      HCV-related liver damage. Our study provides new findings about the association
      of HPgV-2 and HCV/HIV-1 and the impact of HPgV-2 infection on HCV replication and
      pathogenesis.

PMID- 29020290
TI  - Implementing Antimicrobial Stewardship in Long-term Care Settings: An Integrative
      Review Using a Human Factors Approach.
AB  - Implementing effective antimicrobial stewardship in long-term care facilities
      (LTCFs) is associated with challenges distinct from those faced by hospitals.
      LTCFs generally care for elderly populations who are vulnerable to infection,
      have prescribers who are often off-site, and have limited access to timely
      diagnostic testing. Identification of feasible interventions in LTCFs is
      important, particularly given the new requirement for stewardship programs by the
      Centers for Medicare and Medicaid Services (CMS). In this integrative review, we
      analyzed published evidence in the context of a human factors engineering
      approach as well as educational interventions to understand aspects of multimodal
      interventions associated with the implementation of successful stewardship
      programs in LTCFs. The outcomes indicate that effective antimicrobial stewardship
      in long-term care is supported by incorporating multidisciplinary education,
      tools integrated into the workflow of nurses and prescribers that facilitate
      review of antibiotic use, and involvement of infectious disease consultants.

PMID- 29020292
TI  - The management of antiplatelet therapy in acute coronary syndrome patients with
      thrombocytopenia: a clinical conundrum.

PMID- 29020291
TI  - Reward Sensitivity and Waiting Impulsivity: Shift towards Reward Valuation away
      from Action Control.
AB  - Background: Impulsivity and reward expectancy are commonly interrelated. Waiting
      impulsivity, measured using the rodent 5-Choice Serial Reaction Time task,
      predicts compulsive cocaine seeking and sign (or cue) tracking. Here, we assess
      human waiting impulsivity using a novel translational task, the 4-Choice Serial
      Reaction Time task, and the relationship with reward cues. Methods: Healthy
      volunteers (n=29) performed the monetary incentive delay task as a functional MRI
      study where subjects observe a cue predicting reward (cue) and wait to respond
      for high (L5), low (L1), or no reward. Waiting impulsivity was tested with the 4
      Choice Serial Reaction Time task. Results: For high reward prospects (L5, no
      reward), greater waiting impulsivity on the 4-CSRT correlated with greater medial
      orbitofrontal cortex and lower supplementary motor area activity to cues. In
      response to high reward cues, greater waiting impulsivity was associated with
      greater subthalamic nucleus connectivity with orbitofrontal cortex and greater
      subgenual cingulate connectivity with anterior insula, but decreased connectivity
      with regions implicated in action selection and preparation. Conclusion: These
      findings highlight a shift towards regions implicated in reward valuation and a
      shift towards compulsivity away from higher level motor preparation and action
      selection and response. We highlight the role of reward sensitivity and
      impulsivity, mechanisms potentially linking human waiting impulsivity with
      incentive approach and compulsivity, theories highly relevant to disorders of
      addiction.

PMID- 29020286
TI  - Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia
      After Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An
      Italian Prospective Multicenter Survey.
AB  - Background: Gram-negative bacteremia (GNB) is a major cause of illness and death
      after hematopoietic stem cell transplantation (HSCT), and updated epidemiological
      investigation is advisable. Methods: We prospectively evaluated the epidemiology
      of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous
      HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI
      study). Using logistic regression methods. we identified risk factors for GNB and
      evaluated the impact of GNB on the 4-month overall-survival after transplant.
      Results: The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT
      and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas
      aeruginosa were the most common isolates. By multivariate analysis, variables
      associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA
      mismatched donor and from cord blood, older age, and duration of severe
      neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no
      antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant
      pathogen was significantly associated with an increased risk of posttransplant
      infection by the same microorganism in allo-HSCT. Colonization by resistant gram
      negative bacteria was significantly associated with an increased rate of
      infection by the same pathogen in both transplant procedures. GNB was
      independently associated with increased mortality at 4 months both in allo-HSCT
      (hazard ratio, 2.13; 95% confidence interval, 1.45-3.13; P <.001) and auto-HSCT
      (2.43; 1.22-4.84; P = .01). Conclusions: Pre-engraftment GNB is an independent
      factor associated with increased mortality rate at 4 months after auto-HSCT and
      allo-HSCT. Previous infectious history and colonization monitoring represent
      major indicators of GNB. Clinical Trials registration: NCT02088840.

PMID- 29020294
TI  - Predicting Resistance to Piperacillin-Tazobactam, Cefepime and Meropenem in
      Septic Patients With Bloodstream Infection Due to Gram-Negative Bacteria.
AB  - Background: Predicting antimicrobial resistance in gram-negative bacteria (GNB)
      could balance the need for administering appropriate empiric antibiotics while
      also minimizing the use of clinically unwarranted broad-spectrum agents. Our
      objective was to develop a practical prediction rule able to identify patients
      with GNB infection at low risk for resistance to piperacillin-tazobactam (PT),
      cefepime (CE), and meropenem (ME). Methods: The study included adult patients
      with sepsis or septic shock due to bloodstream infections caused by GNB admitted
      between 2008 and 2015 from Barnes-Jewish Hospital. We used multivariable logistic
      regression analyses to describe risk factors associated with resistance to the
      antibiotics of interest (PT, CE, and ME). Clinical decision trees were developed
      using the recursive partitioning algorithm CHAID (chi2 Automatic Interaction
      Detection). Results: The study included 1618 consecutive patients. Prevalence
      rates for resistance to PT, CE, and ME were 28.6%, 21.8%, and 8.5%, respectively.
      Prior antibiotic use, nursing home residence, and transfer from an outside
      hospital were associated with resistance to all 3 antibiotics. Resistance to ME
      was specifically linked with infection attributed to Pseudomonas or Acinetobacter
      spp. Discrimination was similar for the multivariable logistic regression and
      CHAID tree models, with both being better for ME than for PT and CE. Recursive
      partitioning algorithms separated out 2 clusters with a low probability of ME
      resistance and 4 with a high probability of PT, CE, and ME resistance.
      Conclusions: With simple variables, clinical decision trees can be used to
      distinguish patients at low, intermediate, or high risk of resistance to PT, CE,
      and ME.

PMID- 29020296
TI  - The assessment of aortic stenosis: looking beyond the valve.

PMID- 29020297
TI  - RE: "TIME SPENT COMMUTING TO WORK AND MENTAL HEALTH: EVIDENCE FROM 13 WAVES OF AN
      AUSTRALIAN COHORT STUDY".

PMID- 29020295
TI  - Improved Retention With 6-Month Clinic Return Intervals for Stable Human
      Immunodeficiency Virus-Infected Patients in Zambia.
AB  - Background: Extending appointment intervals for stable HIV-infected patients in
      sub-Saharan Africa can reduce patient opportunity costs and decongest overcrowded
      facilities. Methods: We analyzed a cohort of stable HIV-infected adults (on
      treatment with CD4 >200 cells/MUL for more than 6 months) who presented for
      clinic visits in Lusaka, Zambia. We used multilevel, mixed-effects logistic
      regression adjusting for patient characteristics, including prior retention, to
      assess the association between scheduled appointment intervals and subsequent
      missed visits (>14 days late to next visit), gaps in medication (>14 days late to
      next pharmacy refill), and loss to follow-up (LTFU; >90 days late to next visit).
      Results: A total of 62084 patients (66.6% female, median age 38, median CD4 438
      cells/MUL) made 501281 visits while stable on antiretroviral therapy. Most visits
      were scheduled around 1-month (25.0% clinical, 44.4% pharmacy) or 3-month
      intervals (49.8% clinical, 35.2% pharmacy), with fewer patients scheduled at 6
      month intervals (10.3% clinical, 0.4% pharmacy). After adjustment and compared to
      patients scheduled to return in 1 month, patients with six-month clinic return
      intervals were the least likely to miss visits (adjusted odds ratio [aOR], 0.20;
      95% confidence interval [CI], 0.17-0.24); miss medication pickups (aOR, 0.47; 95%
      CI 0.39-0.57), and become LTFU prior to the next visit (aOR, 0.41; 95% CI, 0.31
      0.54). Conclusions: Six-month clinic return intervals were associated with
      decreased lateness, gaps in medication, and LTFU in stable HIV-infected patients
      and may represent a promising strategy to reduce patient burdens and decongest
      clinics.

PMID- 29020299
TI  - Lifestyle in population-based colorectal cancer screening over 2-year follow-up.
AB  - Background: Colorectal cancer (CRC) screening may cause changes in health-related
      lifestyle. In 2010, Finnish Mass Screening Registry began a study on psychosocial
      effects of CRC screening. This article examines whether there are differential
      developments in self-reported lifestyle at ages 59-61 years among CRC screening
      invitees and non-contacted controls. Methods: A population-based random sample of
      10 648 Finnish adults born in 1951 and living in the municipalities voluntary
      involved in the CRC screening programme were sent a lifestyle questionnaire in
      2010. In 2011, the cohort was randomised (1 : 1) for their first ever CRC
      screening at age 60 or for controls. The questionnaires were repeated in 2012 for
      all. From both survey rounds, 2508 pairs of completed questionnaires were
      available for analysis from the screening group and 2387 from the control group.
      The outcome was 2-year change in total lifestyle index of CRC risk factors (diet,
      physical activity, body mass index, alcohol consumption and smoking). Results:
      Total lifestyle index decreased throughout the follow-up in both the screening
      group [odds ratio (OR) = 0.80, 95% confidence interval (CI) 0.72-0.90] and in the
      control group (OR = 0.80, CI 0.71-0.90) indicating no difference in lifestyle
      changes between groups. There was also no significant difference by screening
      participation: the change in score was similar in those participating screening
      (OR 0.81, CI 0.72-0.92) and in those invited, but not participating (OR 0.75, CI
      0.55-1.03). Conclusion: Present study found no unfavourable changes in total
      lifestyle in the studied age group due to CRC screening. Results are reassuring
      from the point of view of CRC screening evaluation.

PMID- 29020293
TI  - Dual Therapy With Darunavir and Ritonavir Plus Lamivudine vs Triple Therapy With
      Darunavir and Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine or
      Abacavir and Lamivudine for Maintenance of Human Immunodeficiency Virus Type 1
      Viral Suppression: Randomized, Open-Label, Noninferiority DUAL-GESIDA 8014-RIS
      EST45 Trial.
AB  - Background: Our objective was to assess the therapeutic noninferiority of dual
      therapy with darunavir/ritonavir and lamivudine compared to triple therapy with
      darunavir/ritonavir plus 2 nucleos(t)ides for maintenance of human
      immunodeficiency virus type 1 (HIV-1) suppression. Methods: This was a
      multicenter, open-label, noninferiority trial (margin 12%). Patients with HIV-1
      RNA <50 copies/mL for 6 months or longer on triple therapy with
      darunavir/ritonavir and 2 nucleos(t)ides (tenofovir disoproxil fumarate and
      emtricitabine or abacavir and lamivudine) and with no resistance were randomized
      to continue therapy (n = 128) or switch to darunavir/ritonavir and lamivudine (n
      = 129). The primary endpoint was the proportion of participants with HIV-RNA <50
      copies/mL after 48 weeks of follow-up according to the snapshot algorithm.
      Results: A total of 249 participants received study drugs (intention-to-treat
      exposed). The proportion of participants with HIV-RNA <50 copies/mL in the dual-
      and triple-therapy arms was 88.9% (112/126) and 92.7% (114/123; difference, 
      3.8%; 95% confidence interval, -11.0 to 3.4), respectively. Four participants in
      the dual-therapy arm and 2 in the triple-therapy arm developed protocol-defined
      virological failure. Switching to dual therapy was associated with a significant
      increase in total, low-density lipoprotein, and high-density lipoprotein (HDL)
      cholesterol, but not in the total-to-HDL cholesterol ratio. Serious adverse
      events and study drug discontinuations due to adverse events occurred in 4.8% vs
      4.9%P = .97) and in 0.8% (1/126) vs 1.6% P = .55) in dual therapy vs triple
      therapy, respectively. Conclusions: Dual therapy with darunavir/ritonavir and
      lamivudine demonstrated noninferior therapeutic efficacy and similar tolerability
      compared to triple therapy. Clinical Trials Registration: NCT02159599.

PMID- 29020298
TI  - Use of a Dual-Antigen Rapid Diagnostic Test to Screen Children for Severe
      Plasmodium falciparum Malaria in a High-Transmission, Resource-Limited Setting.
AB  - Background: In rural areas, many patients with malaria seek care at peripheral
      health facilities or community case management programs. While this strategy is
      effective for the management of uncomplicated malaria, severe malaria
      necessitates prompt detection and referral to facilities with adequate resources.
      Methods: In this prospective, observational cohort study, we assessed the
      accuracy of a dual-band (histidine-rich protein-2/pan-lactate dehydrogenase
      [HRP2/pLDH]) rapid diagnostic test (RDT) to differentiate uncomplicated from
      severe malaria. We included children aged <12 years who presented to a rural
      clinic in western Uganda with a positive HRP2 or HRP2/pLDH RDT. We estimated the
      test characteristics of a dual-antigen (HRP2+/pLDH+) band positive RDT compared
      to World Health Organization-defined clinical and laboratory criteria to detect
      severe malaria. Results: A total of 2678 children underwent testing for malaria
      with an RDT, and 83 (9.0%) satisfied criteria for severe malaria. The sensitivity
      and specificity of a HRP2+/pLDH+ result for severe malaria was 97.6% (95%
      confidence interval [CI], 90.8%-99.6%) and 75.6% (95% CI, 73.8%-77.4%),
      respectively. An HRP2+/pLDH+ result was significantly more sensitive (97.6% vs
      68.7%, P < .001) for the detection of severe malaria compared to algorithms that
      incorporate screening for danger signs. Conclusions: A positive dual-antigen
      (HRP2/pLDH) RDT has higher sensitivity than the use of clinical manifestations to
      detect severe malaria, making it a promising tool in the triage of children with
      malaria in low-resource settings. Additional work is needed to operationalize
      diagnostic and treatment algorithms that include dual-antigen RDTs to avoid over
      referral.

PMID- 29020301
TI  - THE AUTHORS REPLY.

PMID- 29020302
TI  - Cerebrovascular diseases in Poland-inconsistent seasonal patterns of
      hospitalisation and mortality.
AB  - Background: A seasonal variation in the incidence of cerebrovascular diseases
      still remains inconsistently evidenced. Herein, we analyse the monthly patterns
      of two health phenomena: hospital admissions and deaths due to these diseases.
      Methods: We identified 69 511 cases of hospital admissions and 14 956 deaths due
      to cerebrovascular diseases (ICD10: I60-I69 and G45) among the inhabitants of
      five Polish voivodeship capitals in 2004-13. The method of time series analysis
      (exponential smoothing with linear trend and monthly additive seasonality) was
      applied to calculate the monthly specific seasonal indices. The monthly variation
      in an in-hospital fatality and nonhospital deaths were also analysed. Results: A
      summer season reduction in number of cases was observed for hospital admissions
      and deaths. Interestingly, the winter season effect is much more complex, mainly
      due to the contribution of December, when a high mortality is accompanied by a
      substantial decrease in the hospitalisation level. This unique discrepancy was
      observed for all the studied cities. Moreover, this month is characterised by a
      notably high in-hospital fatality. However, neither the number of non-hospital
      deaths nor the average length of hospital stay or the kind of hospitalised
      diseases evidenced that cerebrovascular problems were more serious in December
      than in any other month. Conclusion: The obtained results confirmed a seasonal
      variation in cerebrovascular diseases among the inhabitants of Polish cities.
      Habitual and administrative limitations in hospital activities observed every
      December do not seem indifferent from the patient health's perspective since they
      may lead to a low hospitalisation level and a high in-hospital fatality.

PMID- 29020300
TI  - Impact of design of coronary stents and length of dual antiplatelet therapies on
      ischaemic and bleeding events: a network meta-analysis of 64 randomized
      controlled trials and 102 735 patients.
AB  - Aims: The differential impact on ischaemic and bleeding events of the type of
      drug-eluting stent [durable polymer stents [DES] vs. biodegradable polymer stents
      vs. bioresorbable scaffolds (BRS)] and length of dual antiplatelet therapy (DAPT)
      remains to be defined. Methods and results: Randomized controlled trials
      comparing different types of DES and/or DAPT durations were selected. The primary
      endpoint was Major Adverse Cardiovascular Events (MACE) [a composite of death,
      myocardial infarction (MI), and target vessel revascularization]. Definite stent
      thrombosis (ST) and single components of MACE were secondary endpoints. The arms
      of interest were: BRS with 12 months of DAPT (12mDAPT), biodegradable polymer
      stent with 12mDAPT, durable polymer stent [everolimus-eluting (EES), zotarolimus
      eluting (ZES)] with 12mDAPT, EES/ZES with <12 months of DAPT, and EES/ZES with
      >12 months of DAPT (DAPT > 12 m). Sixty-four studies with 150 arms and 102 735
      patients were included. After a median follow-up of 20 months, MACE rates were
      similar in the different arms of interest. EES/ZES with DAPT > 12 m reported a
      lower incidence of MI than the other groups, while BRS showed a higher rate of ST
      when compared to EES/ZES, irrespective of DAPT length. A higher risk of major
      bleedings was observed for DAPT > 12 m as compared to shorter DAPT. Conclusion:
      Durable and biodegradable polymer stents along with BRS report a similar rate of
      MACE irrespective of DAPT length. Fewer MI are observed with EES/ZES with DAPT >
      12 m, while a higher rate of ST is reported for BRS when compared to EES/ZES,
      independently from DAPT length. Stent type may partially affect the outcome
      together with DAPT length.

PMID- 29020303
TI  - Risk of Venous Thromboembolism Following Hemorrhagic Fever With Renal Syndrome: A
      Self-controlled Case Series Study.
AB  - Background: Bleeding is associated with viral hemorrhagic fevers; however,
      thromboembolic complications have received less attention. Hemorrhagic fever with
      renal syndrome (HFRS) is a mild viral hemorrhagic fever caused by Puumala
      hantavirus. We previously identified HFRS as a risk factor for myocardial
      infarction and stroke, but the risk for venous thromboembolism (VTE), including
      deep vein thrombosis (DVT) and pulmonary embolism (PE), is unknown. Methods:
      Personal identity numbers from the Swedish HFRS database were cross-linked with
      the National Patient register to obtain information on all causes for
      hospitalization during 1964 to 2013. The self-controlled case series method was
      used to calculate the incidence rate ratio (IRR) for first VTE, DVT, and PE
      during 1998 to 2013. Results: From 7244 HFRS patients, there were 146 with a
      first VTE of which 74 were DVT and 78 were PE, and 6 patients had both DVT and
      PE. The overall risk for a VTE was significantly higher during the first 2 weeks
      following HFRS onset, with an IRR of 64.3 (95% confidence interval [CI], 36.3
      114). The corresponding risk for a DVT was 45.9 (95% CI, 18-117.1) and for PE,
      76.8 (95% CI, 37.1-159). Sex interacted significantly with the association
      between HFRS and VTE, with females having a higher risk compared with males.
      Conclusions: A significantly increased risk for VTE was found in the time period
      following HFRS onset. It is important to keep this in mind and monitor HFRS
      patients, and possibly other viral hemorrhagic fever patients, for early symptoms
      of VTE.

PMID- 29020304
TI  - Identification of a targeted and testable antiarrhythmic therapy for long-QT
      syndrome type 2 using a patient-specific cellular model.
AB  - Aims: Loss-of-function mutations in the hERG gene causes long-QT syndrome type 2
      (LQT2), a condition associated with reduced IKr current. Four different mutation
      classes define the molecular mechanisms impairing hERG. Among them, Class 2
      mutations determine hERG trafficking defects. Lumacaftor (LUM) is a drug acting
      on channel trafficking already successfully tested for cystic fibrosis and its
      safety profile is well known. We hypothesize that LUM might rescue also hERG
      trafficking defects in LQT2 and exert anti-arrhythmic effects. Methods and
      results: From five LQT2 patients, we generated lines of induced pluripotent stem
      cell-derived cardiomyocytes (iPSC-CMs) harbouring Class 1 and 2 mutations. The
      effects of LUM on corrected field potential durations (cFPD) and calcium-handling
      irregularities were verified by multi electrode array and by calcium transients
      imaging, respectively. Molecular analysis was performed to clarify the mechanism
      of action of LUM on hERG trafficking and calcium handling. Long-QT syndrome type
      2 induced pluripotent stem cell-derived cardiomyocytes mimicked the clinical
      phenotypes and showed both prolonged cFPD (grossly equivalent to the QT interval)
      and increased arrhythmias. Lumacaftor significantly shortened cFPD in Class 2
      iPSC-CMs by correcting the hERG trafficking defect. Furthermore, LUM seemed to
      act also on calcium handling by reducing RyR2S2808 phosphorylation in both Class
      1 and 2 iPSC-CMs. Conclusion: Lumacaftor, a drug already in clinical use, can
      rescue the pathological phenotype of LQT2 iPSC-CMs, particularly those derived
      from Class 2 mutated patients. Our results suggest that the use of LUM in LQT2
      patients not protected by beta-blockers is feasible and may represent a novel
      therapeutic option.

PMID- 29020305
TI  - Reply to Lipcsey.

PMID- 29020307
TI  - Follow-up Blood Cultures in Gram-Negative Bacteremia: Are They Needed?
AB  - Background: Bloodstream infections remain a major cause of morbidity and
      mortality. Gram-negative bacilli (GNB) bacteremia is typically transient and
      usually resolves rapidly after the initiation of appropriate antibiotic therapy
      and source control. The optimal duration of treatment and utility of follow-up
      blood cultures (FUBC) have not been studied in detail. Currently, the management
      of gram-negative bacteremia is determined by clinical judgment. To investigate
      the value of repeat blood cultures, we analyzed 500 episodes of bacteremia to
      determine frequency of FUBC and identify risk factors for persistent bacteremia.
      Methods: Of 500 episodes of bacteremia, we retrospectively analyzed 383 (77%)
      that had at least 1 FUBC. We sought information regarding presumed source of
      bacteremia, antibiotic status at the time of FUBC, antibiotic susceptibility,
      presence of fever, comorbidities (intravenous central lines, urinary catheters,
      diabetes mellitus, AIDS, end-stage renal disease, and cirrhosis), need for
      intensive care, and mortality. Results: Antibiotic use did not affect the rate of
      positivity of FUBC, unless bacteria were not sensitive to empiric antibiotic.
      Fever on the day of FUBC was associated with higher rates of positive FUBC for
      gram-positive cocci (GPC) but not GNB. Mortality and care in the intensive care
      unit were not associated with positive FUBC. Seventeen FUBC and 5 FUBC were drawn
      for GNB and GPC to yield 1 positive result. Conclusions: FUBC added little value
      in the management of GNB bacteremia. Unrestrained use of blood cultures has
      serious implications for patients including increased healthcare costs, longer
      hospital stays, unnecessary consultations, and inappropriate use of antibiotics.

PMID- 29020306
TI  - Lithium and Tamoxifen Modulate Behavior and Protein Kinase C Activity in the
      Animal Model of Mania Induced by Ouabain.
AB  - Background: The intracerebroventricular injection of ouabain, a specific
      inhibitor of the Na+/K+-adenosine-triphosphatase (Na+/K+-ATPase) enzyme, induces
      hyperactivity in rats in a putative animal model of mania. Several evidences have
      suggested that the protein kinase C signaling pathway is involved in bipolar
      disorder. In addition, it is known that protein kinase C inhibitors, such as
      lithium and tamoxifen, are effective in treating acute mania. Methods: In the
      present study, we investigated the effects of lithium and tamoxifen on the
      protein kinase C signaling pathway in the frontal cortex and hippocampus of rats
      submitted to the animal model of mania induced by ouabain. We showed that ouabain
      induced hyperlocomotion in the rats. Results: Ouabain increased the protein
      kinase C activity and the protein kinase C and MARCKS phosphorylation in frontal
      cortex and hippocampus of rats. Lithium and tamoxifen reversed the behavioral and
      protein kinase C pathway changes induced by ouabain. These findings indicate that
      the Na+/K+-ATPase inhibition can lead to protein kinase C alteration.
      Conclusions: The present study showed that lithium and tamoxifen modulate changes
      in the behavior and protein kinase C signalling pathway alterations induced by
      ouabain, underlining the need for more studies of protein kinase C as a possible
      target for treatment of bipolar disorder.

PMID- 29020309
TI  - Colistin Area Under the Time-Concentration in Children Treated With Intravenous
      Loading Dose and Maintenance Therapy.

PMID- 29020308
TI  - Management of Latent Tuberculosis Infection Among Healthcare Workers: 10-Year
      Experience at a Single Center.
AB  - Background: The risk of infection with Mycobacterium tuberculosis among
      healthcare workers (HCWs) is estimated to be higher than the general population.
      However, HCW acceptance and compliance with available latent tuberculosis
      infection (LTBI) treatment regimens has been problematic. Recently, regimens have
      become available that might improve HCW acceptance and compliance with LTBI
      treatment. Methods: A retrospective single-center review of Employee Health and
      Wellness Services records of all HCWs diagnosed with LTBI was conducted. HCWs
      diagnosed with LTBI were offered 9-month isoniazid (INH), 4-month rifampin (RIF),
      weekly rifapentine/isoniazid (RPT/INH) for 12 weeks, or no treatment. Acceptance,
      completion rates, and side effects were reported for each regimen. Comparisons of
      regimens were assessed using Fisher exact test. Results: Between 2005 and 2014,
      363 of 927 (39%) HCWs diagnosed with LTBI accepted treatment. Of 363, 202 chose
      INH, 106 RIF, and 55 RPT/INH. Completion rates for each regimen were 58%, 80%,
      and 87%, respectively. HCWs were significantly more likely to have completed
      treatment with RIF (P < .0001) or RPT/INH (P < .0001) than INH. Rates of
      discontinuation owing to side effects were 35% for INH, 21% for RIF, and 10% for
      RPT/INH. Discontinuation of therapy due to side effects was significantly more
      frequent in the INH than the RPT/INH group (P = .0042). Conclusions: Completion
      of RIF and RPT/INH for LTBI in an HCW population is more likely than INH. Rates
      of discontinuation due to side effects were lower among those taking RPT/INH.
      Shorter LTBI treatment regimens should be more widely considered for HCWs in the
      United States.

PMID- 29020311
TI  - Noncarbapenem beta-Lactams for the Treatment of Extended-Spectrum beta-Lactamase
      Infections: What Are the Remaining Drugs Outside the United States?

PMID- 29020310
TI  - Levofloxacin Prophylaxis During Induction Therapy for Pediatric Acute
      Lymphoblastic Leukemia.
AB  - Background: Infection is the most important cause of treatment-related morbidity
      and mortality in pediatric patients treated for acute lymphoblastic leukemia
      (ALL). Although routine in adults with leukemia, antibacterial prophylaxis is
      controversial in pediatrics because of insufficient evidence for its efficacy or
      antibiotic choice and concerns about promoting antibiotic resistance and
      Clostridium difficile infection. Methods: This was a single-center, observational
      cohort study of patients with newly diagnosed ALL, comparing prospectively
      collected infection-related outcomes in patients who received no prophylaxis,
      levofloxacin prophylaxis, or other prophylaxis during induction therapy on the
      total XVI study. A propensity score-weighted logistic regression model was used
      to adjust for confounders. Results: Of 344 included patients, 173 received no
      prophylaxis, 69 received levofloxacin prophylaxis, and 102 received other
      prophylaxis regimens. Patients receiving prophylaxis had longer duration of
      neutropenia. Prophylaxis reduced the odds of febrile neutropenia, likely
      bacterial infection, and bloodstream infection by >=70%. Levofloxacin prophylaxis
      alone reduced these infections, but it also reduced cephalosporin,
      aminoglycoside, and vancomycin exposure and reduced the odds of C. difficile
      infection by >95%. No increase in breakthrough infections with antibiotic
      resistant organisms was seen, but this cannot be excluded. Conclusions: This is
      the largest study to date of antibacterial prophylaxis during induction therapy
      for pediatric ALL and the first to include a broad-spectrum fluoroquinolone.
      Prophylaxis prevented febrile neutropenia and systemic infection. Levofloxacin
      prophylaxis also minimized the use of treatment antibiotics and drastically
      reduced C. difficile infection. Although long-term antibiotic-resistance
      monitoring is needed, these data support using targeted prophylaxis with
      levofloxacin in children undergoing induction chemotherapy for ALL. Clinical
      Trials Registration: NCT00549848.

PMID- 29020313
TI  - Trends in Invasive Pneumococcal Disease in Cancer Patients After the Introduction
      of 7-valent Pneumococcal Conjugate Vaccine: A 20-year Longitudinal Study at a
      Major Urban Cancer Center.
AB  - Background: Rates of invasive pneumococcal disease (IPD) declined since routine
      childhood immunization with the 7-valent pneumococcal conjugate vaccine (PCV7) in
      2000. We studied the impact of PCV7 on the incidence of IPD in cancer patients.
      Methods: This was a retrospective analysis of adult and pediatric patients
      treated at Memorial Sloan Kettering Cancer Center from 1992 to 2012. Recovery of
      Streptococcus pneumoniae from a sterile site defined IPD. IPD incidence was
      calculated as cases per 1,000 unique patient-visits per year (UPV). IPD incidence
      was calculated for the periods: "before PCV7" (1992-2000), "after PCV7" (2001
      2010) and "after PCV13" (2011-2012). Results: Of 343 IPD cases, 165, 155, and 23
      cases occurred "before PCV7," "after PCV7" and "after PCV13" respectively. The
      IPD incidence declined from 0.43 "before PCV7" to 0.17 "after PCV7" (95%
      confidence interval [CI]: 0.33-0.46, P < .001) and 0.11 "after PCV13" (95% CI:
      0.42-0.96, P = .004). Adults with hematologic malignancies and children had the
      highest incidence. In patients 1-4 years old, the incidence declined from 11.2
      "before PCV7" to 2.38 "after PCV7" (79% decrease, 95% CI: 0.1-0.4, P < .001). In
      patients with hematologic malignancies, the incidence declined from 2.55 "before
      PCV7" to 0.92 "after PCV7" (64% decrease, 95% CI: 0.27-0.47, P < .001).
      Conclusions: The incidence of IPD among cancer patients sharply declined after
      introduction of PCV7; especially in high risk groups. The decline in adults
      suggests an indirect effect from PCV7 childhood vaccination.

PMID- 29020312
TI  - Explaining the impact of poverty on old-age frailty in Europe: material,
      psychosocial and behavioural factors.
AB  - Background: Previous research found poverty to be associated with adverse health
      outcomes among older adults but the factors that translate low economic resources
      into poor physical health are not well understood. The goal of this analysis was
      to assess the impact of material, psychosocial, and behavioural factors as well
      as education in explaining the poverty-health link. Methods: In total, 28 360
      observations from 11 390 community-dwelling respondents (65+) in the Survey of
      Health, Ageing and Retirement in Europe (2004-13, 10 countries) were analysed.
      Multilevel growth curve models were used to assess the impact of combined income
      and asset poverty risk on old-age frailty (frailty index) and associated pathway
      variables. Results: In total, 61.8% of the variation of poverty risk on frailty
      level was explained by direct and indirect effects. Results stress the role of
      material and particularly psychosocial factors such as perceived control and
      social isolation, whereas the role of health behaviour was negligible.
      Conclusion: We suggest to strengthen social policy and public health efforts in
      order to fight poverty and its deleterious health effects from early age on as
      well as to broaden the scope of interventions with regard to psychosocial
      factors.

PMID- 29020315
TI  - Performance of Rapid Diagnostic Testing in Patients with Suspected Malaria in
      Cambodia, a Low-Endemicity Country Aiming for Malaria Elimination.

PMID- 29020316
TI  - Machine Learning for Healthcare: On the Verge of a Major Shift in Healthcare
      Epidemiology.
AB  - The increasing availability of electronic health data presents a major
      opportunity in healthcare for both discovery and practical applications to
      improve healthcare. However, for healthcare epidemiologists to best use these
      data, computational techniques that can handle large complex datasets are
      required. Machine learning (ML), the study of tools and methods for identifying
      patterns in data, can help. The appropriate application of ML to these data
      promises to transform patient risk stratification broadly in the field of
      medicine and especially in infectious diseases. This, in turn, could lead to
      targeted interventions that reduce the spread of healthcare-associated pathogens.
      In this review, we begin with an introduction to the basics of ML. We then move
      on to discuss how ML can transform healthcare epidemiology, providing examples of
      successful applications. Finally, we present special considerations for those
      healthcare epidemiologists who want to use and apply ML.

PMID- 29020314
TI  - Improved outcomes in patients with ST-elevation myocardial infarction during the
      last 20 years are related to implementation of evidence-based treatments:
      experiences from the SWEDEHEART registry 1995-2014.
AB  - Aims: Impact of changes of treatments on outcomes in ST-elevation myocardial
      infarction (STEMI) patients in real-life health care has not been documented.
      Methods and results: All STEMI cases (n = 105.674) registered in the nation-wide
      SWEDEHEART registry between 1995 and 2014 were included and followed for fatal
      and non-fatal outcomes for up to 20 years. Most changes in treatment and outcomes
      occurred from 1994 to 2008. Evidence-based treatments increased: reperfusion from
      66.2 to 81.7%; primary percutaneous coronary intervention: 4.5 to 78.0%; dual
      antiplatelet therapy from 0 to 89.6%; statin: 14.1 to 93.6%; beta-blocker: 78.2
      to 91.0%, and angiotensin-converting-enzyme/angiotensin-2-receptor inhibitors:
      40.8 to 85.2% (P-value for-trend <0.001 for all). One-year mortality decreased
      from 22.1 to 14.1%. Standardized incidence ratio compared with the general
      population decreased from 5.54 to 3.74 (P < 0.001). Cardiovascular (CV) death
      decreased from 20.1 to 11.1%, myocardial infarction (MI) from 11.5 to 5.8%;
      stroke from 2.9 to 2.1%; heart failure from 7.1 to 6.2%. After standardization
      for differences in demography and baseline characteristics, the change of 1-year
      CV-death or MI corresponded to a linear trend of 0.915 (95% confidence interval:
      0.906-0.923) per 2-year period which no longer was significant, 0.997 (0.984
      1.009), after adjustment for changes in treatment. The changes in treatment and
      outcomes were most pronounced from 1994 to 2008. Conclusion: Gradual
      implementation of new and established evidence-based treatments in STEMI patients
      during the last 20 years has been associated with prolonged survival and lower
      risk of recurrent ischaemic events, although a plateauing is seen since around
      2008.

PMID- 29020318
TI  - Reply to Rossi et al.

PMID- 29020320
TI  - Corrigendum to: 'Clinical outcomes of state-of-the-art percutaneous coronary
      revascularization in patients with de novo three vessel disease: 1-year results
      of the SYNTAX II study.

PMID- 29020317
TI  - Cost-Effectiveness of One-Time Hepatitis C Screening Strategies Among Adolescents
      and Young Adults in Primary Care Settings.
AB  - Background: High hepatitis C virus (HCV) rates have been reported in young people
      who inject drugs (PWID). We evaluated the clinical benefit and cost-effectiveness
      of testing among youth seen in communities with a high overall number of reported
      HCV cases. Methods: We developed a decision analytic model to project quality
      adjusted life years (QALYs), costs (2016 US$), and incremental cost-effectiveness
      ratios (ICERs) of 9 strategies for 1-time testing among 15- to 30-year-olds seen
      at urban community health centers. Strategies differed in 3 ways: targeted vs
      routine testing, rapid finger stick vs standard venipuncture, and ordered by
      physician vs by counselor/tester using standing orders. We performed
      deterministic and probabilistic sensitivity analyses (PSA) to evaluate
      uncertainty. Results: Compared to targeted risk-based testing (current standard
      of care), routine testing increased the lifetime medical cost by $80 and
      discounted QALYs by 0.0013 per person. Across all strategies, rapid testing
      provided higher QALYs at a lower cost per QALY gained and was always preferred.
      Counselor-initiated routine rapid testing was associated with an ICER of
      $71000/QALY gained. Results were sensitive to offer and result receipt rates.
      Counselor-initiated routine rapid testing was cost-effective (ICER <$100000/QALY)
      unless the prevalence of PWID was <0.59%, HCV prevalence among PWID was <16%,
      reinfection rate was >26 cases per 100 person-years, or reflex confirmatory
      testing followed all reactive venipuncture diagnostics. In PSA, routine rapid
      testing was the optimal strategy in 90% of simulations. Conclusions: Routine
      rapid HCV testing among 15- to 30-year-olds may be cost-effective when the
      prevalence of PWID is >0.59%.

PMID- 29020319
TI  - Tuberculosis Case Finding With Combined Rapid Point-of-Care Assays (Xpert MTB/RIF
      and Determine TB LAM) in HIV-Positive Individuals Starting Antiretroviral Therapy
      in Mozambique.
AB  - Background: Tuberculosis is a major health concern in several countries, and
      effective diagnostic algorithms for use in human immunodeficiency virus (HIV)
      positive patients are urgently needed. Methods: At prescription of antiretroviral
      therapy, all patients in 3 Mozambican health centers were screened for
      tuberculosis, with a combined approach: World Health Organization (WHO) 4-symptom
      screening (fever, cough, night sweats, and weight loss), a rapid test detecting
      mycobacterial lipoarabinomannan in urine (Determine TB LAM), and a molecular
      assay performed on a sputum sample (Xpert MTB/RIF; repeated if first result was
      negative). Patients with positive LAM or Xpert MTB/RIF results were referred for
      tuberculosis treatment. Results: Among 972 patients with a complete diagnostic
      algorithm (58.5% female; median CD4 cell count, 278/MUL; WHO HIV stage I, 66.8%),
      98 (10.1%) tested positive with Xpert (90, 9.3%) or LAM (34, 3.5%) assays.
      Compared with a single-test Xpert strategy, dual Xpert tests improved case
      finding by 21.6%, LAM testing alone improved it by 13.5%, and dual Xpert tests
      plus LAM testing improved it by 32.4%. Rifampicin resistance in Xpert-positive
      patients was infrequent (2.5%). Among patients with positive results, 22 of 98
      (22.4%) had no symptoms at WHO 4-symptom screening. Patients with tuberculosis
      diagnosed had significantly lower CD4 cell counts and hemoglobin levels, more
      advanced WHO stage, and higher HIV RNA levels. Fifteen (15.3%) did not start
      tuberculosis treatment, mostly owing to rapidly deteriorating clinical conditions
      or logistical constraints. The median interval between start of the diagnostic
      algorithm and start of tuberculosis treatment was 7 days. Conclusions: The
      prevalence of tuberculosis among Mozambican HIV-positive patients starting
      antiretroviral therapy was 10%, with limited rifampicin resistance. Use of
      combined point-of-care tests increased case finding, with a short time to
      treatment. Interventions are needed to remove logistical barriers and prevent
      presentation in very advanced HIV/tuberculosis disease.

PMID- 29020321
TI  - Comparison of a Novel Human Rabies Monoclonal Antibody to Human Rabies
      Immunoglobulin for Postexposure Prophylaxis: A Phase 2/3, Randomized, Single
      Blind, Noninferiority, Controlled Study.
AB  - Background: Lack of access to rabies immunoglobulin (RIG) contributes to high
      rabies mortality. A recombinant human monoclonal antibody (SII RMAb) was tested
      in a postexposure prophylaxis (PEP) regimen in comparison with a human RIG (HRIG)
      containing PEP regimen. Methods: This was a phase 2/3, randomized, single-blind,
      noninferiority study conducted in 200 participants with World Health Organization
      category III suspected rabies exposures. Participants received either SII RMAb or
      HRIG (1:1 ratio) in wounds and, if required, intramuscularly on day 0, along with
      5 doses of rabies vaccine intramuscualarly on days 0, 3, 7, 14 and 28. The
      primary endpoint was the ratio of the day 14 geometric mean concentration (GMC)
      of rabies virus neutralizing activity (RVNA) as measured by rapid fluorescent
      focus inhibition test for SII RMAb recipients relative to HRIG recipients.
      Results: One hundred ninety-nine participants received SII RMAb (n = 101) or HRIG
      (n = 98) and at least 1 dose of vaccine. The day 14 GMC ratio of RVNA for the SII
      RMAb group relative to the HRIG group was 4.23 (96.9018% confidence interval
      [CI], 2.59-6.94) with a GMC of of 24.90 IU/mL (95% CI, 18.94-32.74) for SII RMAb
      recipients and 5.88 IU/mL (95% CI, 4.11-8.41) for HRIG recipients. The majority
      of local injection site and systemic adverse reactions reported from both groups
      were mild to moderate in severity. Conclusions: A PEP regimen containing SII RMAb
      was safe and demonstrated noninferiority to HRIG PEP in RVNA production. The
      novel monoclonal potentially offers a safe and potent alternative for the passive
      component of PEP and could significantly improve the management of bites from
      suspected rabid animals. Clincical Trials Registration: CTRI/2012/05/002709.

PMID- 29020322
TI  - Trends in Methicillin-Resistant Staphylococcus aureus Hospitalizations in the
      United States, 2010-2014.
AB  - Data from the National Inpatient Sample show that the decrease in
      hospitalizations related to methicillin-resistant Staphylococcus aureus (MRSA)
      infections between 2010 and 2014 primarily reflected declines in skin and soft
      tissue infections. Hospitalizations related to invasive MRSA remained largely
      unchanged.

PMID- 29020323
TI  - Corticosteroids in Patients Hospitalized With Community-Acquired Pneumonia:
      Systematic Review and Individual Patient Data Metaanalysis.
AB  - Background: Our aim was to evaluate the benefits and harms of adjunctive
      corticosteroids in adults hospitalized with community-acquired pneumonia (CAP)
      using individual patient data from randomized, placebo-controlled trials and to
      explore subgroup differences. Methods: We systematically searched Medline,
      Embase, Cochrane Central, and trial registers (all through July 2017). Data from
      1506 individual patients in 6 trials were analyzed using uniform outcome
      definitions. We investigated prespecified effect modifiers using multivariable
      hierarchical regression, adjusting for pneumonia severity, age, and clustering
      effects. Results: Within 30 days of randomization, 37 of 748 patients (5.0%)
      assigned to corticosteroids and 45 of 758 patients (5.9%) assigned to placebo
      died (adjusted odds ratio [aOR], 0.75; 95% confidence interval [CI], .46 to 1.21;
      P &#x003D; .24). Time to clinical stability and length of hospital stay were
      reduced by approximately 1 day with corticosteroids (-1.03 days; 95% CI, -1.62 to
      -.43; P &#x003D; .001 and -1.15 days; 95% CI, -1.75 to -.55; P < .001,
      respectively). More patients with corticosteroids had hyperglycemia (160 [22.1%]
      vs 88 [12.0%]; aOR, 2.15; 95% CI, 1.60 to 2.90; P < .001) and CAP-related
      rehospitalization (33 [5.0%] vs 18 [2.7%]; aOR, 1.85; 95% CI, 1.03 to 3.32; P
      &#x003D; .04). We did not find significant effect modification by CAP severity or
      degree of inflammation. Conclusions: Adjunct corticosteroids for patients
      hospitalized with CAP reduce time to clinical stability and length of hospital
      stay by approximately 1 day without a significant effect on overall mortality but
      with an increased risk for CAP-related rehospitalization and hyperglycemia.

PMID- 29020324
TI  - Mumps Outbreak in a Highly Vaccinated University-Affiliated Setting Before and
      After a Measles-Mumps-Rubella Vaccination Campaign-Iowa, July 2015-May 2016.
AB  - Background: In response to a mumps outbreak at the University of Iowa and
      surrounding community, university, state, and local health officials implemented
      a vaccination campaign targeting students <25 years of age with an additional
      dose of measles-mumps-rubella (MMR) vaccine. More than 4700 vaccine campaign
      doses were administered; 97% were documented third doses. We describe the
      epidemiology of the outbreak before and after the campaign, focusing on cases in
      university students. Methods: Mumps cases were identified from reportable disease
      databases and university health system records. Detailed information on student
      cases was obtained from interviews, medical chart abstractions, university and
      state vaccination records, and state public health laboratory results. Pre- and
      postcampaign incidence among students, university faculty/staff, and community
      members <25 vs >=25 years old were compared using Fisher exact test.
      Multivariable regression modeling was performed to identify variables associated
      with a positive mumps polymerase chain reaction test. Results: Of 453 cases in
      the county, 301 (66%) occurred in university students. Student cases were
      primarily undergraduates (90%) and highly vaccinated (86% had 2 MMR doses, and
      12% had 3 MMR doses). Fewer cases occurred in students after the campaign (75
      [25%]) than before (226 [75%]). Cases in the target group (students <25 years of
      age) declined 9% postcampaign (P=.01). A positive mumps polymerase chain reaction
      test was associated with the presence of parotitis and early sample collection,
      and inversely associated with recent receipt of MMR vaccine. Conclusions:
      Following a large additional dose MMR vaccination campaign, fewer mumps cases
      occurred overall and in the target population.

PMID- 29020325
TI  - Adapting Reactive Case Detection Strategies for falciparum Malaria in a Low
      Transmission Area in Cambodia.
AB  - Reactive case detection around falciparum malaria cases in Cambodia presents a
      low output. We improved it by including individuals occupationally coexposed with
      index case patients and using polymerase chain reaction-based diagnosis. The
      positivity rate increased from 0.16% to 3.9%.

PMID- 29020326
TI  - Empagliflozin across the stages of diabetic heart disease.

PMID- 29020327
TI  - Cognitive changes in prevalent and incident cardiovascular disease: a 12-year
      follow-up in the Maastricht Aging Study (MAAS).
AB  - Aims: Cardiovascular disease (CVD) has been suggested to accelerate cognitive
      decline and to be a risk factor for dementia, but still little is known about the
      cognitive course after a first cardiovascular event. Therefore, the present study
      aims to investigate the cognitive trajectories in both prevalent and incident CVD
      over a 12-year time period in the general population. Methods and results:
      Cognitively healthy participants (age 24-82 years, n = 1823) of a prospective
      cohort study were serially assessed at baseline, 6 and 12 years. Verbal memory,
      executive function, and information processing speed were analysed in adults with
      prevalent, incident, and no CVD. Random effects models were used to test the
      association between CVD and change in cognitive function over time. At baseline,
      participants with prevalent CVD showed more decline in memory and information
      processing speed than healthy controls. Participants with incident CVD also
      showed more decline in these cognitive domains, but this was only significant in
      the follow-up period from 6 to 12 years. Associations were more pronounced in
      participants aged younger than 65 years at baseline, and in sub-analyses with
      angina pectoris or myocardial infarction as the most prevalent CVD conditions.
      Conclusion: Prevalent and incident CVD predict cognitive decline in middle-aged
      individuals. Findings for incident CVD suggest that the onset of decline is
      linked in time with the vascular event itself. Timely CVD management may delay
      the onset of decline.

PMID- 29020328
TI  - Early Fecal Microbiota Transplantation Improves Survival in Severe Clostridium
      difficile Infections.
AB  - Background: Severe Clostridium difficile infections (CDIs) are associated with a
      high mortality rate despite medical and/or surgical treatment. Fecal microbiota
      transplantation (FMT) prevents recurrences, but its effect on survival has been
      shown only in patients with O27 ribotype CDI. Here, we investigated whether early
      FMT could improve survival in hospitalized CDI patients, particularly those with
      severe infection. Methods: We performed a retrospective cohort study between May
      2013 and April 2016 at the infectious diseases department of the North University
      Hospital of Marseille, France. Patients received either medical treatment alone
      or treatment with early FMT. The primary outcome was the 3-month mortality rate.
      Results: A total of 111 patients were included: 66 in the FMT group and 45 in the
      non-FMT group. No patient underwent surgery. The O27 ribotype (odds ratio [OR],
      3.64 [95% confidence interval {CI}, 1.05- 12.6], P = .04), severe CDI (OR, 9.62
      [95% CI, 2.16-42.8], P = .003), and FMT (OR, 0.13 [95% CI, .04-.44], P = .001)
      were independent predictors of 3-month mortality. FMT improved survival in severe
      cases (OR, 0.08 [95% CI, .016-.34], P = .001) but not in nonsevere cases (OR,
      1.07 [95% CI, .02-56.3], P = .97), independent of age, sex, comorbidities
      (Charlson score), and ribotype. The number of severe patients who needed to be
      treated to save 1 life at 3 months was 2. Conclusions: Early FMT dramatically
      reduces mortality and should be proposed as a first-line treatment for severe
      CDI. Further studies are needed to clarify complications and contraindications.
      Surgery should be reassessed in this context.

PMID- 29020331
TI  - Mechanical circulatory support: harm without benefit? Fascinated by devices,
      cardiologists may lose common sense.

PMID- 29020330
TI  - Enhanced Sexually Transmitted Infection Screening for Mycoplasma genitalium in
      Human Immunodeficiency Virus -Infected US Air Force Personnel.
AB  - Three-site genital and extragenital screening for Mycoplasma genitalium in 102
      asymptomatic Air Force members with human immunodeficiency virus (HIV) infection
      revealed 19 (18.6%) cases of M. genitalium, commonly (58%) in rectal samples.
      Because M. genitalium is associated with both HIV acquisition and transmission,
      these findings suggest that it should be included in routine screening of HIV
      infected individuals for sexually transmitted infections.

PMID- 29020332
TI  - Dependency of Vaccine Efficacy on Preexposure and Age: A Closer Look at a
      Tetravalent Dengue Vaccine.
AB  - Background: A recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV)
      was licensed for children aged >=9 years in a few countries, but the dependence
      of vaccine efficacy on baseline immunity status and age groups has not been fully
      characterized. Methods: Combining the 2 phase 3 trials CYD14 and CYD15, we
      estimated the vaccine efficacy for each of the 4 serotypes of dengue virus
      (DENV), as well as all serotypes combined, simultaneously stratified by baseline
      immunity status and age group, while accounting for uncertainty in the baseline
      immunity status of subjects. Results: Baseline seropositive subjects showed high
      efficacy for all serotypes: 70.2% (95% confidence interval [CI], 57.4%-80.1%) for
      dengue serotype 1 (DENV-1), 67.9% (95% CI, 49.9%-82.0%) for DENV-2, 77.5% (95%
      CI, 64.3%-90.2%) for DENV-3, 89.9% (95% CI, 79.8%-99.9%) for DENV-4, and 75.4%
      (95% CI, 68.3%-81.6%) overall. In contrast, baseline seronegative subjects showed
      moderate efficacy against DENV-4 (51.2% [95% CI, 20.0%-72.8%]) but no significant
      efficacy against other serotypes. Among seropositive children, the overall
      efficacy tended to increase with age: 35.9% (95% CI, -7.6% to 69.3%) for children
      <=5 years old, 65.6% (95% CI, 40.3%-84.2%) for those 6-8 years old, 73.4% (95%
      CI, 62.6%-82.1%) for those 9-11 years old, and 80.6% (95% CI, 72.9%-87.3%) for
      those 12 years or older. Conclusions: The CYD-TDV vaccine was highly efficacious
      for all dengue serotypes among children aged >5 years who have acquired baseline
      immunity from previous exposure. Increasing vaccine efficacy with age was not
      fully explained by increasing prevalence of baseline immunity with age.

PMID- 29020329
TI  - Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents
      and Young Adults With Human Immunodeficiency Virus Infection Being Treated With
      Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial.
AB  - Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density
      (BMD). We hypothesized that vitamin D3 (VITD3) would increase BMD in youth
      receiving TDF. Methods: This was a randomized, double-blind, placebo-controlled
      trial of directly observed VITD3 vs placebo every 4 weeks for 48 weeks in youth
      aged 16-24 years with HIV, RNA load <200 copies/mL, taking TDF-containing
      combination antiretroviral therapy (TDF-cART) for >=180 days. Participants (N =
      214) received a daily multivitamin containing VITD3 400 IU and calcium 162 mg,
      plus monthly randomized VITD3 50000 IU (n = 109) or placebo (n = 105). Outcome
      was change from baseline to week 48 in lumbar spine BMD (LSBMD). Data presented
      are median (Q1, Q3). Results: Participants were aged 22.0 (21.0, 23.0) years, 84%
      were male, and 74% were black/African American. At baseline, 62% had 25-hydroxy
      vitamin D (25-OHD) <20 ng/mL. Multivitamin adherence was 49% (29%, 69%), and
      VITD3/placebo adherence 100% (100%, 100%). Vitamin D intake was 2020 (1914, 2168)
      and 284 (179, 394) IU/day, and serum 25-OHD concentration was 36.9 (30.5, 42.4)
      and 20.6 (14.4, 25.8) ng/mL at 48 weeks in VITD3 and placebo groups, respectively
      (P < .001). From baseline to week 48, LSBMD increased by 1.15% (-0.75% to 2.74%)
      in the VITD3 group (n = 99; P < .001) and 0.09% (-1.49% to 2.61%) in the placebo
      group (n = 89; P = .25), without between-group difference (P = .12). VITD3 group
      changes occurred with baseline 25-OHD <20 ng/mL (1.17% [-.82% to 2.90%]; P =
      .004) and >=20 ng/mL (0.93% [-.26% to 2.15%]; P = .033). Conclusions: For youth
      taking TDF-cART, LSBMD increased through 48 weeks with VITD3 plus multivitamin,
      but not with placebo plus multivitamin, independent of baseline vitamin D status.
      Clinical Trials Registration: NCT01751646.

PMID- 29020333
TI  - Thrombo-embolic prevention after transcatheter aortic valve implantation.
AB  - Transcatheter aortic valve implantation (TAVI) has emerged as a valuable
      treatment alternative to surgical aortic valve replacement among patients with
      symptomatic aortic stenosis at increased surgical risk. The rapid technological
      evolution from early to current-generation TAVI systems with low-profile delivery
      catheters, bioprosthetic valves with proven midterm durability, and improved
      positioning and retrieval features have made important contributions to the
      widespread clinical use of this minimal invasive therapy. Although peri
      procedural and long-term thrombotic and bleeding events after TAVI remain a
      relevant concern, the optimal antithrombotic strategy and duration to mitigate
      these risks remain unclear. This review provides an overview of recent insights
      in this field, and highlights current and future antithrombotic trials focusing
      on optimizing outcomes in patients undergoing TAVI.

PMID- 29020334
TI  - Lumbar Puncture Performed Promptly or After Neuroimaging in Acute Bacterial
      Meningitis in Adults: A Prospective National Cohort Study Evaluating Different
      Guidelines.
AB  - Background: Early treatment is pivotal for favorable outcome in acute bacterial
      meningitis (ABM). Lumbar puncture (LP) is the diagnostic key. The aim was to
      evaluate the effect on outcome of adherence to European Society of Clinical
      Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of
      America (IDSA), and Swedish guidelines regarding neuroimaging before LP. Methods:
      The cohort comprised 815 adult ABM patients in Sweden registered prospectively
      between 2008 and 2015. Primary endpoint was in-hospital mortality and secondary
      endpoint was favorable outcome at 2-6 months of follow-up. Results: Indications
      for neuroimaging before LP existed in 7%, 32%, and 65% according to Swedish,
      ESCMID, and IDSA guidelines, respectively. The adjusted odds ratio (aOR) was 0.48
      (95% confidence interval [CI], .26-.89) for mortality and 1.52 (95% CI, 1.08
      2.12) for favorable outcome if Swedish guidelines were followed. ESCMID guideline
      adherence resulted in aOR of 0.68 (95% CI, .38-1.23) for mortality and 1.05 (95%
      CI, .75-1.47) for favorable outcome. Following IDSA recommendations resulted in
      aOR of 1.09 (95% CI, .61-1.95) for mortality and 0.59 (95% CI, .42-.82) for
      favorable outcome. Performing prompt vs neuroimaging-preceded LP was associated
      with aOR of 0.38 (95% CI, .18-.77) for mortality and 2.11 (95% CI, 1.47-3.00) for
      favorable outcome. The beneficial effect of prompt LP was observed regardless of
      mental status and immunosuppression. Conclusions: Adherence to Swedish guidelines
      in ABM is associated with decreased mortality and increased favorable outcome in
      contrast to adherence to ESCMID or IDSA recommendations. Our findings support
      that impaired mental status and immunocompromised state should not be considered
      indications for neuroimaging before LP in patients with suspected ABM.

PMID- 29020336
TI  - Corrigendum to: Rhythm for Life, in Germany.

PMID- 29020335
TI  - Human Immunodeficiency Virus (HIV) Drug Resistance in African Infants and Young
      Children Newly Diagnosed With HIV: A Multicountry Analysis.
AB  - Background: Programs for the prevention of mother-to-child transmission (PMTCT)
      of human immunodeficiency virus (HIV) have been scaled up in many low- and middle
      income countries. However, HIV drug resistance (HIVDR) data among HIV-1-infected
      young children remain limited. Methods: Surveys of pretreatment HIVDR among
      children aged <18 months who were diagnosed with HIV through early infant
      diagnosis were conducted in 5 sub-Saharan African countries (Mozambique,
      Swaziland, South Africa, Uganda, and Zimbabwe) between 2011 and 2014 following
      World Health Organization (WHO) guidance. Deidentified demographic and clinical
      data were used to explore risk factors associated with nonnucleoside reverse
      transcriptase inhibitor (NNRTI) resistance. Results: Among the 1450 genotypes
      analyzed, 1048 had accompanying demographic and clinical data. The median age of
      children was 4 months; 50.4% were female. HIV from 54.1% showed resistance to 1
      or more antiretroviral (ARV) drugs, with 53.0% and 8.8% having resistance to 1 or
      more NNRTI or nucleoside reverse transcriptase inhibitors, respectively. NNRTI
      resistance was particularly high in children exposed to ARV drugs through PMTCT;
      adjusted odds ratios were 1.8 (95% confidence interval [CI], 1.3-2.6) for
      maternal exposure only and 2.4 (CI, 1.6-3.6) for neonatal exposure only.
      Conclusions: Protease inhibitor-based regimens in children aged <3 years are
      currently recommended by WHO, but the implementation of this recommendation is
      suboptimal. These results reinforce the urgent need to overcome barriers to
      scaling up pediatric protease inhibitor-based regimens in sub-Saharan Africa and
      underscore the need to accelerate the study and approval of integrase inhibitors
      for use in young children.

PMID- 29020337
TI  - Refining the prognostic impact of functional mitral regurgitation in chronic
      heart failure.
AB  - Aims: Significant efforts are currently undertaken to reduce functional mitral
      regurgitation (FMR) in patients with chronic heart failure in the hope to improve
      prognosis. We aimed to assess the prognostic impact of FMR in heart failure with
      reduced ejection fraction (HFrEF) under optimal medical therapy (OMT) and various
      conditions of HFrEF. We further intended to identify a heart failure phenotype,
      where FMR is most likely a driving force and not a mere bystander of the disease.
      Methods and results: We prospectively included 576 consecutive HFrEF patients
      into our long-term observational study. Functional [i.e. New York Heart
      Association (NYHA) class], echocardiographic, invasive haemodynamic, and
      biochemical (i.e. NT-proBNP, MR-proANP, MR-proADM, CT-proET-1, copeptin)
      measurements were performed at baseline. During a median follow-up of 62 months
      (interquartile range 52-76), 47% of patients died. Severe FMR was a significant
      predictor of mortality [hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.34
      2.30; P < 0.001], independent of clinical (adjusted HR 1.61, 95% CI 1.22-2.12; P
      = 0.001), and echocardiographic (adjusted HR 1.46, 95% CI 1.09-1.94; P = 0.01)
      confounders, OMT (adjusted HR 1.81, 95% CI 1.25-2.63; P = 0.002), and
      neurohumoral activation (adjusted HR 1.38, 95% CI 1.03-1.84; P = 0.03).
      Subanalysis revealed that severe FMR was associated with poor outcome in an
      intermediate-failure phenotype of HFrEF i.e. patients with NYHA class II
      (adjusted HR 2.17, 95% CI 1.07-4.44; P = 0.03) and III (adjusted HR 1.80, 95% CI
      1.17-2.77; P = 0.008), moderately reduced left ventricular function (adjusted HR
      2.37, 95% CI 1.36-4.12; P = 0.002), and within the second quartile (871-2360
      pg/mL) of NT-proBNP (adjusted HR 2.16, 95% CI 1.22-3.86; P = 0.009). Conclusion:
      In a patient cohort under OMT, the adverse prognostic impact of FMR is given
      predominantly in a sub-cohort of a specific intermediate-failure phenotype-well
      defined functionally, haemodynamically, biochemically, and morphologically.

PMID- 29020338
TI  - Is Moderate Alcohol Consumption Safe for Human Immunodeficiency Virus/Hepatitis C
      Virus-Coinfected Women?

PMID- 29020339
TI  - Use of Viral Load as a Surrogate Marker in Clinical Studies of Cytomegalovirus in
      Solid Organ Transplantation: A Systematic Review and Meta-analysis.
AB  - Symptomatic cytomegalovirus (CMV) disease has been the standard endpoint for
      clinical trials in organ transplant recipients. Viral load may be a more relevant
      endpoint due to low frequency of disease. We performed a meta-analysis and
      systematic review of the literature. We found several lines of evidence to
      support the validity of viral load as an appropriate surrogate end-point,
      including the following: (1) viral loads in CMV disease are significantly greater
      than in asymptomatic viremia (odds ratio, 9.3 95% confidence interval, 4.6-19.3);
      (2) kinetics of viral replication are strongly associated with progression to
      disease; (3) pooled incidence of CMV viremia and disease is significantly lower
      during prophylaxis compared with the full patient follow-up period (viremia
      incidence: 3.2% vs 34.3%; P < .001) (disease incidence: 1.1% vs 13.0%; P < .001);
      (4) treatment of viremia prevented disease; and (5) viral load decline correlated
      with symptom resolution. Based on the analysis, we conclude that CMV load is an
      appropriate surrogate endpoint for CMV trials in organ transplant recipients.

PMID- 29020340
TI  - Relationship Between Viremia and Specific Organ Damage in Ebola Patients: A
      Cohort Study.
AB  - Background: Pathogenesis of Ebola virus disease remains poorly understood. We
      used concomitant determination of routine laboratory biomarkers and Ebola viremia
      to explore the potential role of viral replication in specific organ damage.
      Methods: We recruited patients with detectable Ebola viremia admitted to the
      EMERGENCY Organizzazione Non Governativa Organizzazione Non Lucrativa di Utilita
      Sociale (ONG ONLUS) Ebola Treatment Center in Sierra Leone. Repeated measure of
      Ebola viremia, alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      bilirubin, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), activated
      prothrombin time (aPTT), international normalized ratio (INR), creatinine, and
      blood urea nitrogen (BUN) were recorded. Patients were followed up from admission
      until death or discharge. Results: One hundred patients (49 survivors and 51
      nonsurvivors) were included in the analysis. Unadjusted analysis to compare
      survivors and nonsurvivors provided evidence that all biomarkers were
      significantly above the normal range and that the extent of these abnormalities
      was generally higher in nonsurvivors than in survivors. Multivariable mixed
      effects models provided strong evidence for a biological gradient (suggestive of
      a direct role in organ damage) between the viremia levels and either ALT, AST,
      CPK LDH, aPTT, and INR. In contrast, no direct linear association was found
      between viremia and either creatinine, BUN, or bilirubin. Conclusions: This study
      provides evidence to support that Ebola virus may have a direct role in muscular
      damage and imbalance of the coagulation system. We did not find strong evidence
      suggestive of a direct role of Ebola virus in kidney damage. The role of the
      virus in liver damage remains unclear, but our evidence suggests that acute
      severe liver injury is not a typical feature of Ebola virus disease.

PMID- 29020341
TI  - Percutaneous short-term active mechanical support devices in cardiogenic shock: a
      systematic review and collaborative meta-analysis of randomized trials.
AB  - Aims: Evidence on the impact on clinical outcome of active mechanical circulatory
      support (MCS) devices in cardiogenic shock (CS) is scarce. This collaborative
      meta-analysis of randomized trials thus aims to investigate the efficacy and
      safety of percutanzeous active MCS vs. control in CS. Methods and results:
      Randomized trials comparing percutaneous active MCS to control in patients with
      CS were identified through searches of medical literature databases. Risk ratios
      (RR) and 95% confidence intervals (95% CI) were calculated to analyse the primary
      endpoint of 30-day mortality and device-related complications including bleeding
      and leg ischaemia. Mean differences (MD) were calculated for mean arterial
      pressure (MAP), cardiac index (CI), pulmonary capillary wedge pressure (PCWP),
      and arterial lactate. Four trials randomizing 148 patients to either
      TandemHeartTM or Impella(r) MCS (n = 77) vs. control (n = 71) were identified. In
      all four trials intra-aortic balloon pumping (IABP) served as control. There was
      no difference in 30-day mortality (RR 1.01, 95% CI 0.70 to 1.44, P = 0.98, I2 =
      0%) for active MCS compared with control. Active MCS significantly increased MAP
      (MD 11.85 mmHg, 95% CI 3.39 to 20.31, P = 0.02, I2 = 32.7%) and decreased
      arterial lactate (MD - 1.36 mmol/L, 95% CI - 2.52 to - 0.19, I2 = 0%, P = 0.02)
      at comparable CI (MD 0.32, 95% CI - 0.24 to 0.87, P = 0.14, I2 = 44.1%) and PCWP
      (MD - 5.59, 95% -15.59 to 4.40, P = 0.14, I2 = 81.1%). No significant difference
      was observed in the incidence of leg ischaemia (RR 2.64, 95% CI 0.83 to 8.39, P =
      0.10, I2 = 0%), whereas the rate of bleeding was significantly increased in MCS
      compared to IABP (RR 2.50, 95% CI 1.55 to 4.04, P < 0.001, I2 = 0%). Conclusion:
      Results of this collaborative meta-analysis do not support the unselected use of
      active MCS in patients with CS complicating AMI.

PMID- 29020342
TI  - Lack of Ovarian Secretions Reverts the Anabolic Action of Olanzapine in Female
      Rats.
AB  - Background: Olanzapine is an orexigenic antipsychotic drug associated with
      serious metabolic adverse effects in humans. Development of valid rodent models
      for antipsychotic-induced metabolic adverse effects is hampered by the fact that
      such effects occur in females only. Estradiol is a predominant female hormone
      that regulates energy balance. We hypothesized that the female-specific
      hyperphagia and weight gain induced by olanzapine in the rat are dependent on the
      presence of estrogens. Methods: Female sham-operated or ovariectomized rats were
      treated with a single injection of olanzapine depot formulation. Food intake,
      body weight, plasma lipids, lipogenic gene expression, energy expenditure, and
      thermogenic markers including brown adipose tissue uncoupling protein 1 protein
      levels were measured. Olanzapine was also administered to ovariectomized rats
      receiving estradiol replacement via the subcutaneous (peripheral) or
      intracerebroventricular route. Results: Orexigenic effects of olanzapine were
      lost in ovariectomized female rats. Ovariectomized rats treated with olanzapine
      had less pronounced weight gain than expected from their food intake.
      Accordingly, brown adipose tissue temperature and protein levels of uncoupling
      protein 1 were elevated. Replacement in ovariectomized rats with either
      peripherally or centrally administered estradiol reduced food intake and body
      weight. Cotreatment with olanzapine blocked the anorexigenic effect of
      peripheral, but not central estradiol. Conclusions: Our results indicate that the
      ovarian hormone estradiol plays an important role in olanzapine-induced
      hyperphagia in female rats and pinpoint the complex effects of olanzapine on the
      balance between energy intake and thermogenesis.

PMID- 29020343
TI  - Disability weights for infectious diseases in four European countries: comparison
      between countries and across respondent characteristics.
AB  - Background: In 2015, new disability weights (DWs) for infectious diseases were
      constructed based on data from four European countries. In this paper, we
      evaluated if country, age, sex, disease experience status, income and educational
      levels have an impact on these DWs. Methods: We analyzed paired comparison
      responses of the European DW study by participants' characteristics with separate
      probit regression models. To evaluate the effect of participants'
      characteristics, we performed correlation analyses between countries and within
      country by respondent characteristics and constructed seven probit regression
      models, including a null model and six models containing participants'
      characteristics. We compared these seven models using Akaike Information
      Criterion (AIC). Results: According to AIC, the probit model including country as
      covariate was the best model. We found a lower correlation of the probit
      coefficients between countries and income levels (range rs: 0.97-0.99, P < 0.01)
      than between age groups (range rs: 0.98-0.99, P < 0.01), educational level (range
      rs: 0.98-0.99, P < 0.01), sex (rs = 0.99, P < 0.01) and disease status (rs =
      0.99, P < 0.01). Within country the lowest correlations of the probit
      coefficients were between low and high income level (range rs = 0.89-0.94, P <
      0.01). Conclusions: We observed variations in health valuation across countries
      and within country between income levels. These observations should be further
      explored in a systematic way, also in non-European countries. We recommend future
      researches studying the effect of other characteristics of respondents on health
      assessment.

PMID- 29020344
TI  - Standardized definitions of structural deterioration and valve failure in
      assessing long-term durability of transcatheter and surgical aortic bioprosthetic
      valves: a consensus statement from the European Association of Percutaneous
      Cardiovascular Interventions (EAPCI) endorsed by the European Society of
      Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery
      (EACTS).

PMID- 29020346
TI  - Reply to Davido et al.

PMID- 29020345
TI  - Plasmodium malariae in Israeli Travelers: A Nationwide Study.
AB  - Background: Little is known about Plasmodium malariae, a relatively rare cause of
      malaria in returned travelers. Recently, polymerase chain reaction (PCR) use for
      malaria diagnosis has enhanced specificity of P. malariae detection. The study
      objective was to describe the unique aspects of P. malariae diagnosis and
      clinical course in travelers. Methods: Malaria is a reportable disease in Israel.
      All PCR-proven P. malariae monoinfections in Israeli travelers between January
      2008 and January 2017 were retrieved from the Ministry of Health Reference
      Parasitology Laboratory. Data regarding method and timing of diagnosis, clinical
      characteristics, and laboratory testing were collected from patient charts.
      Results: Eighteen patients with P. malariae were included. All cases were
      acquired in Africa. During the study period, the relative proportion of P.
      malariae increased (2%-10% of all malaria cases). Malaria was identified by blood
      smear in 10 of 18 patients (56%) on admission, and by rapid antigen test in 5 of
      18 (29%) patients only, while P. malariae speciation was correctly identified by
      smear in 2 of 18 (11%) patients. Though all patients reported fever, only 4 of 18
      (22%) described a quartan fever course. In 7 of 18 (39%) patients, malaria was
      contracted despite prophylactic treatment. Five patients had prolonged prepatent
      periods (median, 55 days), all of whom received prior prophylaxis. Conclusions:
      The relative proportion of P. malariae is on the rise. Diagnosis in routine
      clinical settings is inadequate due to the low sensitivity and specificity of
      blood smears. PCR should be considered when clinical suspicion is high.
      Prophylaxis failure, which caused delayed clinical presentation, was documented.

PMID- 29020347
TI  - Transcatheter aortic valve implantation in lower-risk patients: what is the
      perspective?
AB  - In the last decade, transcatheter aortic valve implantation (TAVI), a disruptive
      technology, has revolutionized the therapy of symptomatic severe aortic stenosis,
      and current guidelines state that the recommendations for TAVI and surgical
      aortic valve replacement (SAVR) are equivalent in patients at high-risk.
      Increased operator experience, technical advances in the new generation of
      transcatheter heart valves (THV) and excellent TAVI results in recently published
      randomized controlled trials have led to the expansion of TAVI indication as an
      alternative to SAVR in intermediate-risk subjects, given appropriate patient
      selection. The time is opportune to examine the role of TAVI in low-risk
      patients, currently the objective of on-going randomized trials. This review aims
      to summarize the available knowledge on TAVI in low- to intermediate-risk
      patients and to discuss the potential advantages and pitfalls TAVI will face in
      this clinical setting.

PMID- 29020349
TI  - A family of diseases in families of patients.

PMID- 29020350
TI  - Monitoring of Parasite Kinetics in Indian Post-Kala-azar Dermal Leishmaniasis.
AB  - Background: The potential reservoirs of leishmaniasis in South Asia include
      relapsed cases of visceral leishmaniasis (VL), patients with post-kala-azar
      dermal leishmaniasis (PKDL), and an asymptomatically infected population.
      Therefore, assessment of cure in terms of parasite clearance, early detection of
      PKDL, and asymptomatic VL are pivotal for ensuring elimination. This study aimed
      to monitor the efficacy of miltefosine and liposomal amphotericin B (LAmB) in
      PKDL based on parasite load. Methods: Patients with PKDL were recruited from the
      dermatology outpatient departments or during active field surveys. Skin biopsies
      were collected at disease presentation, immediately at the end of treatment, and
      6 months later. The presence of parasite DNA was assessed by internal transcribed
      spacer-1 polymerase chain reaction, and quantified by amplification of parasite
      kinetoplastid DNA. Results: At disease presentation (n = 184), the median
      parasite load was 5229 (interquartile range [IQR], 896-50898)/MUg genomic DNA
      (gDNA). Miltefosine cleared the parasites to <10 in the macular (n = 17) and
      polymorphic (n = 21) variants, and remained so up to 6 months later (<10
      parasites). LAmB reduced the parasite burden substantially in macular (n = 34;
      2128 [IQR, 544-5763]/ug gDNA) and polymorphic PKDL (n = 36; 2541 [IQR, 650
      9073]/ug gDNA). Importantly, in patients who returned 6 months later (n = 38), a
      resurgence of parasites was evident, as the parasites increased to 5665 (IQR,
      1840-17067)/ug gDNA. Conclusions: This study established that quantifying
      parasite load is an effective approach for monitoring patients with PKDL, wherein
      miltefosine demonstrated near-total parasite clearance and resolution of
      symptoms. However, in cases treated with LAmB, the persistence of parasites
      suggested treatment inadequacy. This needs immediate redressal in view of the
      leishmaniasis elimination program targeted for 2020.

PMID- 29020351
TI  - Reply to Frencken et al.

PMID- 29020348
TI  - Kinetics of Double-Stranded DNA Viremia After Allogeneic Hematopoietic Cell
      Transplantation.
AB  - Background: Improved understanding of double-stranded DNA (dsDNA) virus kinetics
      after hematopoietic cell transplantation (HCT) would facilitate development of
      therapeutic strategies. Methods: We tested weekly plasma samples from 404
      patients through day 100 after allogeneic HCT for cytomegalovirus (CMV), human
      herpesvirus (HHV) 6A and 6B, BK polyomavirus (BKV), adenovirus (AdV), and Epstein
      Barr virus (EBV) using quantitative polymerase chain reaction. Episodes lasting
      <=1 week were defined as blips and >1 week as persistent. We described virus
      specific kinetics, analyzed the association of virus area under the curve (AUC)
      with overall mortality, and identified risk factors for persistent episodes.
      Results: We identified 428 episodes of CMV, 292 of BKV, 224 of HHV-6B, 46 of AdV,
      and 53 of EBV. CMV and BKV had the highest proportions of persistent episodes
      (68% and 80%, respectively). Detection and kinetics varied by virus. HHV-6B
      episodes reached maximum levels fastest and had the shortest intervals between
      detection and end-organ disease. End-organ disease occurred within 14 days of
      viremia in 68% of cases, generally during persistent episodes. For all viruses,
      higher viral load AUC increased risk for overall mortality through day 365,
      persistent episodes had higher viral load than blips, and higher first positive
      viral load significantly increased risk for persistent episodes. First viral load
      >2 log10 copies/mL (range, 2.04-3.06 per virus) had high specificity for
      persistent episodes. Conclusions: Persistent high viral load dsDNA viremia
      episodes after allogeneic HCT predict mortality. Virus-specific kinetics can
      guide timing and thresholds for early intervention in studies of novel agents.

PMID- 29020352
TI  - The MIDA Mortality Risk Score: development and external validation of a
      prognostic model for early and late death in degenerative mitral regurgitation.
AB  - Aims: In degenerative mitral regurgitation (DMR), lack of mortality scores
      predicting death favours misperception of individual patients' risk and
      inappropriate decision-making. Methods and results: The Mitral Regurgitation
      International Database (MIDA) registries include 3666 patients (age 66 +/- 14
      years; 70% males; follow-up 7.8 +/- 5.0 years) with pure, isolated, DMR
      consecutively diagnosed by echocardiography at tertiary (European/North/South
      American) centres. The MIDA Score was derived from the MIDA-Flail-Registry (2472
      patients with DMR and flail leaflet-Derivation Cohort) by weighting all guideline
      provided prognostic markers, and externally validated in the MIDA-BNP-Registry
      (1194 patients with DMR and flail leaflet/prolapse-Validation Cohort). The MIDA
      Score ranged from 0 to 12 depending on accumulating risk factors. In predicting
      total mortality post-diagnosis, the MIDA Score showed excellent concordance both
      in Derivation Cohort (c = 0.78) and Validation Cohort (c = 0.81). In the whole
      MIDA population (n = 3666 patients), 1-year mortality with Scores 0, 7-8, and 11
      12 was 0.4, 17, and 48% under medical management and 1, 7, and 14% after surgery,
      respectively (P < 0.001). Five-year survival with Scores 0, 7-8, and 11-12 was 98
      +/- 1, 57 +/- 4, and 21 +/- 10% under medical management and 99 +/- 1, 82 +/- 2,
      and 57 +/- 9% after surgery (P < 0.001). In models including all guideline
      provided prognostic markers and the EuroScoreII, the MIDA Score provided
      incremental prognostic information (P <= 0.002). Conclusion: The MIDA Score may
      represent an innovative tool for DMR management, being able to position a given
      patient within a continuous spectrum of short- and long-term mortality risk,
      either under medical or surgical management. This innovative prognostic indicator
      may provide a specific framework for future clinical trials aiming to compare new
      technologies for DMR treatment in homogeneous risk categories of patients.

PMID- 29020354
TI  - The definition of the Brugada syndrome.
AB  - Brugada syndrome (BS) is an inherited disease characterized by a coved-type ST
      segment elevation in the right precordial leads and increased risk of sudden
      cardiac death (SCD), in the absence of structural abnormalities. The cornerstone
      of BS diagnosis and definition, is its characteristic ECG pattern that can be
      present spontaneously or unmasked by drugs. Brugada syndrome was first described
      25 years ago; paradoxically, in an era of great technological development, a new
      syndrome was described with a technology developed almost a century before. Great
      scientific knowledge has been gathered since the description of the syndrome. The
      better understanding of its pathophysiology and genetic basis has led to several
      modifications in its definition. Despite these facts, the essential, the
      description of the specific ECG pattern has remained almost unchanged since the
      initial report. In this article, we present the definition of the BS, the
      rationale behind it and our thoughts about its future.

PMID- 29020353
TI  - Differential effects of PCSK9 variants on risk of coronary disease and ischaemic
      stroke.
AB  - Aims: PCSK9 genetic variants that have large effects on low-density lipoprotein
      cholesterol (LDL-C) and coronary heart disease (CHD) have prompted the
      development of therapeutic PCSK9-inhibition. However, there is limited evidence
      that PCSK9 variants are associated with ischaemic stroke (IS). Methods and
      results: Associations of the loss-of-function PCSK9 genetic variant (rs11591147;
      R46L), and five additional PCSK9 variants, with IS and IS subtypes
      (cardioembolic, large vessel, and small vessel) were estimated in a meta-analysis
      involving 10 307 IS cases and 19 326 controls of European ancestry. They were
      then compared with the associations of these variants with LDL-C levels (in up to
      172 970 individuals) and CHD (in up to 60 801 CHD cases and 123 504 controls).
      The rs11591147 T allele was associated with 0.5 mmol/L lower LDL-C level (P = 9 *
      10-143) and 23% lower CHD risk [odds ratio (OR): 0.77, 95% confidence interval
      (CI): 0.69-0.87, P = 7 * 10-6]. However, it was not associated with risk of IS
      (OR: 1.04, 95% CI: 0.84-1.28, P = 0.74) or IS subtypes. Information from
      additional PCSK9 variants also indicated consistently weaker effects on IS than
      on CHD. Conclusion: PCSK9 genetic variants that confer life-long lower PCSK9 and
      LDL-C levels appear to have significantly weaker, if any, associations with risk
      of IS than with risk of CHD. By contrast, similar proportional reductions in
      risks of IS and CHD have been observed in randomized trials of therapeutic PCSK9
      inhibition. These findings have implications for our understanding of when
      Mendelian randomization can be relied upon to predict the effects of therapeutic
      interventions.

PMID- 29020355
TI  - Effects of empagliflozin on risk for cardiovascular death and heart failure
      hospitalization across the spectrum of heart failure risk in the EMPA-REG
      OUTCOME(r) trial.
AB  - Aims: Empagliflozin reduced the risk of cardiovascular (CV) death and heart
      failure (HF) hospitalizations in patients with type 2 diabetes (T2D) and
      established CV disease (CVD) in the EMPA-REG OUTCOME(r) trial. We investigated
      whether the benefit of empagliflozin was observed across the spectrum of HF risk.
      Methods and results: Seven thousand and twenty patients with T2D (HbA1c 7-10% and
      eGFR > 30 mL/min/1.73 m2) were treated with empagliflozin 10 or 25 mg, or placebo
      once daily and followed for median 3.1 years. In patients without HF at baseline
      (89.9%), we derived the 5-year risk for incident HF using the 9-variable Health
      ABC HF Risk score [classified as low-to-average (<10%), high (10-20%), and very
      high (>= 20%)]. Overall, 67.2% of the population had low-to-average, 24.2% high,
      and 5.1% very high 5-year HF risk. Across these groups, the effect on CV death
      and HF hospitalization with empagliflozin was consistent [hazard ratio 0.71 (95%
      confidence interval: 0.52, 0.96), 0.52 (0.36, 0.75), and 0.55 (0.30, 1.00),
      respectively]. Effects on CV death in the ostensibly highest HF risk group (HF at
      baseline and/or incident HF during the trial) in whom 37.9% of the overall CV
      deaths occurred, was also beneficial [0.67 (0.47, 0.97)], yet, similar benefits
      were seen in the lower risk patients. Conclusion: In patients with T2D and
      established CVD, a sizeable proportion without HF at baseline are at high or very
      high risk for HF outcomes, indicating the need for active case finding in this
      patient population. Empagliflozin consistently improved HF outcomes both in
      patients at low or high HF risk.

PMID- 29020357
TI  - The role of cardiologists in stroke prevention and treatment: position paper of
      the European Society of Cardiology Council on Stroke.

PMID- 29020358
TI  - Cardiac rejuvenation: a new hope in the presbycardia nightmare.

PMID- 29020356
TI  - A common missense variant of LILRB5 is associated with statin intolerance and
      myalgia.
AB  - Aims: A genetic variant in LILRB5 (leukocyte immunoglobulin-like receptor
      subfamily-B) (rs12975366: T > C: Asp247Gly) has been reported to be associated
      with lower creatine phosphokinase (CK) and lactate dehydrogenase (LDH) levels.
      Both biomarkers are released from injured muscle tissue, making this variant a
      potential candidate for susceptibility to muscle-related symptoms. We examined
      the association of this variant with statin intolerance ascertained from
      electronic medical records in the GoDARTS study. Methods and results: In the
      GoDARTS cohort, the LILRB5 Asp247 variant was associated with statin intolerance
      (SI) phenotypes; one defined as having raised CK and being non-adherent to
      therapy [odds ratio (OR) 1.81; 95% confidence interval (CI): 1.34-2.45] and the
      other as being intolerant to the lowest approved dose of a statin before being
      switched to two or more other statins (OR 1.36; 95% CI: 1.07-1.73). Those
      homozygous for Asp247 had increased odds of developing both definitions of
      intolerance. Importantly the second definition did not rely on CK elevations.
      These results were replicated in adjudicated cases of statin-induced myopathy in
      the PREDICTION-ADR consortium (OR1.48; 95% CI: 1.05-2.10) and for the development
      of myalgia in the JUPITER randomized clinical trial of rosuvastatin (OR1.35, 95%
      CI: 1.10-1.68). A meta-analysis across the studies showed a consistent
      association between Asp247Gly and outcomes associated with SI (OR1.34; 95% CI:
      1.16-1.54). Conclusion: This study presents a novel immunogenetic factor
      associated with statin intolerance, an important risk factor for cardiovascular
      outcomes. The results suggest that true statin-induced myalgia and non-specific
      myalgia are distinct, with a potential role for the immune system in their
      development. We identify a genetic group that is more likely to be intolerant to
      their statins.

PMID- 29020359
TI  - Sofosbuvir-based Interferon-Free Direct Acting Antiviral Regimens for Heart
      Transplant Recipients With Chronic Hepatitis C Virus Infection.
AB  - We assessed the effectiveness and safety of sofosbuvir (SOF) combined with
      ledipasvir (LDV) or daclatasvir (DCV) in 12 heart transplant recipients with
      chronic hepatitis C virus (HCV). The sustained virologic response (SVR12) rate
      was 100% [95% confidence interval [CI]: 75.8%-100%]. All patients tolerated
      treatment well without interruption, death, or serious adverse events.

PMID- 29020362
TI  - Reply to Drancourt.

PMID- 29020361
TI  - Higher Mortality Despite Early Antiretroviral Therapy in Human Immunodeficiency
      Virus and Hepatitis B Virus (HBV)-Coinfected Patients With High HBV Replication.
AB  - Background: In human immunodeficiency virus (HIV)-infected patients, hepatitis B
      virus (HBV) coinfection increases the risk of disease progression. Tenofovir plus
      emtricitabine/lamivudine (TDF/XTC)-based antiretroviral therapy (ART), which
      suppresses HIV and HBV replication, has the potential for decreasing this risk.
      Here, we analyze the association between HBV replication, early ART, and
      mortality in West African adults. Methods: The Temprano randomized controlled
      trial assessed the benefits of immediately initiating vs deferring ART in HIV
      infected adults with high CD4 counts. After trial completion, participants
      continued follow-up in a posttrial phase. We analyzed the association between HBV
      status, immediate ART, and mortality over the entire trial and posttrial follow
      up using multivariable Cox proportional hazards regression. Results: A total of
      2052 HIV-infected adults (median baseline CD4 count, 464 cells/MUL) were followed
      for 9394 person-years. At baseline, 1862 (91%) were HIV monoinfected and 190 (9%)
      HIV/HBV coinfected. Of the latter, 135 (71%) had plasma HBV DNA <2000 IU/mL and
      55 (29%) HBV DNA >=2000 IU/mL. The 60-month probability of death was 11.8% (95%
      confidence interval [CI], 5.4%-24.5%) in coinfected patients with HBV DNA >=2000
      IU/mL; 4.4% (95% CI, 1.9%-10.4%) in coinfected patients with HBV DNA <2000 IU/mL;
      and 4.2% (95% CI, 3.3%-5.4%) in HIV-monoinfected patients. Adjusting for ART
      strategy (immediate vs deferred), the hazard ratio of death was 2.74 (95% CI,
      1.26-5.97) in coinfected patients with HBV DNA >=2000 IU/mL and 0.90 (95% CI, .36
      2.24) in coinfected patients with HBV DNA <2000 IU/mL compared to HIV
      monoinfected patients. There was no interaction between ART strategy and HBV
      status for mortality. Conclusions: African HIV/HBV-coinfected adults with high
      HBV replication remain at heightened risk of mortality in the early ART era.
      Further studies are needed to assess interventions combined with early ART to
      decrease mortality in this population. Clinical Trials Registration: NCT00495651.

PMID- 29020360
TI  - Epidemiology, Clinical Features, and Outcome of Infective Endocarditis due to
      Abiotrophia Species and Granulicatella Species: Report of 76 Cases, 2000-2015.
AB  - Background: Infective endocarditis (IE) caused by Abiotrophia (ABI) and
      Granulicatella (GRA) species is poorly studied. This work aims to describe and
      compare the main features of ABI and GRA IE. Methods: We performed a
      retrospective study of 12 IE institutional cases of GRA or ABI and of 64 cases
      published in the literature (overall, 38 ABI and 38 GRA IE cases). Results:
      ABI/GRA IE represented 1.51% of IE cases in our institution between 2000 and
      2015, compared to 0.88% of HACEK (Haemophilus, Aggregatibacter, Cardiobacterium,
      Eikenella, Kingella)-related IE and 16.62% of Viridans group streptococci (VGS)
      IE. Institutional ABI/GRA IE case characteristics were comparable to that of VGS,
      but periannular complications were more frequent (P = .008). Congenital heart
      disease was reported in 4 (10.5%) ABI and in 11 (28.9%) GRA cases (P = .04).
      Mitral valve was more frequently involved in ABI than in GRA (P < .001). Patient
      sex, prosthetic IE, aortic involvement, penicillin susceptibility, and surgical
      treatment were comparable between the genera. New-onset heart failure was the
      most frequent complication without genera differences (P = .21). Five (13.2%) ABI
      patients and 2 (5.3%) GRA patients died (P = .23). Factors associated with higher
      mortality were age (P = .02) and new-onset heart failure (P = .02). The genus
      (GRA vs ABI) was not associated with higher mortality (P = .23). Conclusions:
      GRA/ABI IE was more prevalent than HACEK IE and approximately one-tenth as
      prevalent as VGS; periannular complications were more frequent. GRA and ABI
      genera IE presented similar clinical features and outcomes. Overall mortality was
      low, and related to age and development of heart failure.

PMID- 29020363
TI  - Pneumonia Mortality in Children Aged <5 Years in 56 Countries: A Retrospective
      Analysis of Trends from 1960 to 2012.
AB  - Background: Pneumonia is now the second leading cause of death for children aged
      <5 years worldwide. However, analyses of the long-term evolution of under-5
      mortality from pneumonia are still scarce in the literature. We aimed to explore
      long-term trends of under-5 mortality from pneumonia in 56 countries from 1960 to
      2012. Methods: Data on under-5 mortality from pneumonia were extracted from the
      World Health Organization mortality database. Long-term trends were assessed for
      56 countries and for 4 national income transition groups. We also used joinpoint
      regression analysis to detect distinct period segments of long-term trends and
      estimate the annual percent of changes of each period segment. Results: The
      average mortality rate from pneumonia for children aged 0-4 years in 56 countries
      declined from 163.0 per 100000 children (95% confidence interval [CI], 119.4 to
      212.8) in 1960 to 9.9 per 100000 children (95% CI, 6.4 to 13.4) in 2012, with an
      average annual percent of change of -5.6% (95% CI, -7.2% to -3.9%). The temporal
      trends of childhood mortality were different between national income transition
      groups. Conclusions: Our findings suggest a striking overall downward trend in
      under-5 mortality from pneumonia between 1960 and 2012. However, the rate and
      absolute terms of decline differ by national income transition group. These
      variable patterns between national income transition groups may inform further
      intervention setting and priority setting.

PMID- 29020365
TI  - The heart-brain connection: from evidence to action.

PMID- 29020366
TI  - Timing, timing, timing: the emerging concept of the 'door to support' time for
      cardiogenic shock.

PMID- 29020364
TI  - Antimicrobial Resistance in Gram-Negative Rods Causing Bacteremia in
      Hematopoietic Stem Cell Transplant Recipients: Intercontinental Prospective Study
      of the Infectious Diseases Working Party of the European Bone Marrow
      Transplantation Group.
AB  - Background: This intercontinental study aimed to study gram-negative rod (GNR)
      resistance in hematopoietic stem cell transplantation (HSCT). Methods: GNR
      bacteremias occurring during 6 months post-HSCT (February 2014-May 2015) were
      prospectively collected, and analyzed for rates and risk factors for resistance
      to fluoroquinolones, noncarbapenem anti-Pseudomonas beta-lactams
      (noncarbapenems), carbapenems, and multidrug resistance. Results: Sixty-five HSCT
      centers from 25 countries in Europe, Australia, and Asia reported data on 655 GNR
      episodes and 704 pathogens in 591 patients (Enterobacteriaceae, 73%;
      nonfermentative rods, 24%; and 3% others). Half of GNRs were fluoroquinolone and
      noncarbapenem resistant; 18.5% carbapenem resistant; 35.2% multidrug resistant.
      The total resistance rates were higher in allogeneic HSCT (allo-HSCT) vs
      autologous HSCT (auto-HSCT) patients (P < .001) but similar in community-acquired
      infections. Noncarbapenem resistance and multidrug resistance were higher in auto
      HSCT patients in centers providing vs not providing fluoroquinolone prophylaxis
      (P < .01). Resistance rates were higher in southeast vs northwest Europe and
      similar in children and adults, excluding higher fluoroquinolone- and beta
      lactam/beta-lactamase inhibitor resistance rates in allo-HSCT adults. Non
      Klebsiella Enterobacteriaceae were rarely carbapenem resistant. Multivariable
      analysis revealed resistance risk factors in allo-HSCT patients: fluoroquinolone
      resistance: adult, prolonged neutropenia, breakthrough on fluoroquinolones;
      noncarbapenem resistance: hospital-acquired infection, breakthrough on
      noncarbapenems or other antibiotics (excluding fluoroquinolones, noncarbapenems,
      carbapenems), donor type; carbapenem resistance: breakthrough on carbapenem,
      longer hospitalization, intensive care unit, previous other antibiotic therapy;
      multidrug resistance: longer hospitalization, breakthrough on beta-lactam/beta
      lactamase inhibitors, and carbapenems. Inappropriate empiric therapy and
      mortality were significantly more common in infections caused by resistant
      bacteria. Conclusions: Our data question the recommendation for fluoroquinolone
      prophylaxis and call for reassessment of local empiric antibiotic protocols.
      Knowledge of pathogen-specific resistance enables early appropriate empiric
      therapy. Monitoring of resistance is crucial. Clinical Trials Registration:
      NCT02257931.

PMID- 29020368
TI  - Social vulnerabilities as determinants of overweight in 2-, 4- and 6-year-old
      Spanish children.
AB  - Background: Differences in obesity prevalence among vulnerable groups exist in
      childhood but it remains unclear whether these differences may be partly
      determined by socioeconomic status (SES), parental body mass index (BMI) and
      early life risk factors. We aimed to explore (i) longitudinal associations
      between belonging to a minority group and being overweight/obese at age 2, 4 and
      6 and (ii) associations between accumulation of social vulnerabilities and being
      overweight/obese at age 6. Methods: In total, 1031 children (53.8% boys) were
      evaluated at birth and re-examined during a 6-year follow-up in a representative
      cohort of Aragon (Spain). Children from minority (vulnerable) groups included
      Spanish Roma/gypsies, Eastern Europeans, Latin Americans and Africans. Two more
      vulnerable groups were defined at baseline as children whose parents reported low
      occupation and education. Ethnicity, SES and parental BMI were collected via
      interviews. We used logistic mixed-effects models and adjusted for parental BMI,
      SES, mother's tobacco use, maternal weight gain, birth weight, infant weight gain
      and breastfeeding practices. Results: Regardless of confounders, Roma/gypsy
      children (OR = 4.63;[1.69-12.70]95%CI) and with Latin American background (OR =
      3.04;[1.59-5.82]95%CI) were more likely to be overweight/obese at age 6 compared
      with non-gypsy Spanish group. Children with three vulnerabilities (OR =
      2.18;[1.31-3.64]95%CI) were more likely to be overweight/obese at age 6 compared
      with children with no vulnerabilities. No associations were found between
      belonging to a minority group and overweight/obesity in children under 6.
      Conclusion: Interventions should target Roma/gypsy children, Latin American
      children and those who accumulate more vulnerabilities as they are at higher risk
      of being overweight/obese at age 6.

PMID- 29020369
TI  - Giant coronary aneurysm exposed on routine echocardiogram.

PMID- 29020370
TI  - Multivessel PCI on its 40th anniversary: finally a match for CABG?

PMID- 29020371
TI  - The importance of no-reflow/microvascular obstruction in the STEMI patient.

PMID- 29020367
TI  - Clinical outcomes of state-of-the-art percutaneous coronary revascularization in
      patients with de novo three vessel disease: 1-year results of the SYNTAX II
      study.
AB  - Aims: To investigate if recent technical and procedural developments in
      percutaneous coronary intervention (PCI) significantly influence outcomes in
      appropriately selected patients with three-vessel (3VD) coronary artery disease.
      Methods and results: The SYNTAX II study is a multicenter, all-comers, open
      label, single arm study that investigated the impact of a contemporary PCI
      strategy on clinical outcomes in patients with 3VD in 22 centres from four
      European countries. The SYNTAX-II strategy includes: heart team decision-making
      utilizing the SYNTAX Score II (a clinical tool combining anatomical and clinical
      factors), coronary physiology guided revascularisation, implantation of thin
      strut bioresorbable-polymer drug-eluting stents, intravascular ultrasound (IVUS)
      guided stent implantation, contemporary chronic total occlusion revascularisation
      techniques and guideline-directed medical therapy. The rate of major adverse
      cardiac and cerebrovascular events (MACCE [composite of all-cause death,
      cerebrovascular event, any myocardial infarction and any revascularisation]) at
      one year was compared to a predefined PCI cohort from the original SYNTAX-I trial
      selected on the basis of equipoise 4-year mortality between CABG and PCI. As an
      exploratory endpoint, comparisons were made with the historical CABG cohort of
      the original SYNTAX-I trial. Overall 708 patients were screened and discussed
      within the heart team; 454 patients were deemed appropriate to undergo PCI. At
      one year, the SYNTAX-II strategy was superior to the equipoise-derived SYNTAX-I
      PCI cohort (MACCE SYNTAX-II 10.6% vs. SYNTAX-I 17.4%; HR 0.58, 95% CI 0.39-0.85,
      P = 0.006). This difference was driven by a significant reduction in the
      incidence of MI (HR 0.27, 95% CI 0.11-0.70, P = 0.007) and revascularisation (HR
      0.57, 95% CI 0.37-0.9, P = 0.015). Rates of all-cause death (HR 0.69, 95% CI 0.27
      1.73, P = 0.43) and stroke (HR 0.69, 95% CI 0.10-4.89, P = 0.71) were similar.
      The rate of definite stent thrombosis was significantly lower in SYNTAX-II (HR
      0.26, 95% CI 0.07-0.97, P = 0.045). Conclusion: At one year, clinical outcomes
      with the SYNTAX-II strategy were associated with improved clinical results
      compared to the PCI performed in comparable patients from the original SYNTAX-I
      trial. Longer term follow-up is awaited and a randomized clinical trial with
      contemporary CABG is warranted. ClinicalTrials.gov Identifier: NCT02015832.

PMID- 29020375
TI  - Food insecurity in Denmark-socio-demographic determinants and associations with
      eating- and health-related variables.
AB  - Background: Food insecurity and its consequences have not received much attention
      in the Nordic, social-democratic welfare states. This study reports the
      prevalence of low and very low food security in Denmark, identifies its socio
      demographic determinants and examines its associations with eating-related and
      health-related outcomes. Methods: A cross-sectional survey with a mixed-mode
      response format (telephone interviewing or Internet). A disproportional
      stratified random sampling design was employed (N = 1877). Main measure was the 6
      item gradient food security construct adapted from the US. Results: Prevalence of
      low and very low food security was 6.0% (95% CI:5.4-8.5%) and 2.4% (95% CI:1.3
      3.3%), respectively. Prevalence was highest in households with disposable income
      below OECD's poverty threshold, households receiving benefits or disability
      pensions, and single-parent households. After socio-demographic adjustment,
      adults from low/very low food secure households had a higher probability of
      eating an unhealthy diet (women: adj.RR 2.82 P < 0.001; men: adj.RR 2.15 P <
      0.01). Adults from low/very low food secure households had lower life
      satisfaction (women: adj.RR 0.49, P < 0.05; men: adj.RR 0.09 P < 0.001) and
      higher risk of psychological distress (women: adj.RR 2.42 P < 0.05; men: adj.RR
      8.95 P < 0.001). Obesity was more prevalent in low/very low food secure women (RR
      2.44 P < 0.05), but not after socio-demographic adjustment. Conclusion: Food
      insecurity in Denmark is associated with adverse factors such as unhealthy diet,
      obesity, life satisfaction, and psychological distress. It is important to widen
      food insecurity research to non-liberal welfare states since low/very low food
      security is negatively associated with unhealthy eating and other health
      indicators, even in a social-democratic welfare state.

PMID- 29020372
TI  - Tolcapone-Enhanced Neurocognition in Healthy Adults: Neural Basis and Predictors.
AB  - Background: Failure of procognitive drug trials in schizophrenia may reflect the
      clinical heterogeneity of schizophrenia, underscoring the need to identify
      biomarkers of treatment sensitivity. We used an experimental medicine design to
      test the procognitive effects of a putative procognitive agent, tolcapone, using
      an electroencephalogram-based cognitive control task in healthy subjects.
      Methods: Healthy men and women (n=27; ages 18-35 years), homozygous for either
      the Met/Met or Val/Val rs4680 genotype, received placebo and tolcapone 200 mg
      orally across 2 test days separated by 1 week in a double-blind, randomized,
      counterbalanced, within-subject design. On each test day, neurocognitive
      performance was assessed using the MATRICS Consensus Cognitive Battery and an
      electroencephalogram-based 5 Choice-Continuous Performance Test. Results:
      Tolcapone enhanced visual learning in low-baseline MATRICS Consensus Cognitive
      Battery performers (d=0.35) and had an opposite effect in high performers
      (d=0.5), and enhanced verbal fluency across all subjects (P=.03) but had no
      effect on overall MATRICS Consensus Cognitive Battery performance. Tolcapone
      reduced false alarm rate (d=0.8) and enhanced frontal P200 amplitude during
      correctly identified nontarget trials (d=0.6) in low-baseline 5 Choice-Continuous
      Performance Test performers and had opposite effects in high performers (d=0.5
      and d=0.25, respectively). Tolcapone's effect on frontal P200 amplitude and false
      alarm rate was correlated (rs=-0.4, P=.05). All neurocognitive effects of
      tolcapone were independent of rs4680 genotype. Conclusion: Tolcapone enhanced
      neurocognition and engaged electroencephalogram measures relevant to cognitive
      processes in specific subgroups of healthy individuals. These findings support an
      experimental medicine model for identifying procognitive treatments and provide a
      strong basis for future biomarker-informed procognitive studies in schizophrenia
      patients.

PMID- 29020373
TI  - Artemether-Lumefantrine Versus Chloroquine for the Treatment of Uncomplicated
      Plasmodium knowlesi Malaria: An Open-Label Randomized Controlled Trial CAN KNOW.
AB  - Background: Plasmodium knowlesi is reported increasingly across Southeast Asia
      and is the most common cause of malaria in Malaysia. No randomized trials have
      assessed the comparative efficacy of artemether-lumefantrine (AL) for knowlesi
      malaria. Methods: A randomized controlled trial was conducted in 3 district
      hospitals in Sabah, Malaysia to compare the efficacy of AL against chloroquine
      (CQ) for uncomplicated knowlesi malaria. Participants were included if they
      weighed >10 kg, had a parasitemia count <20000/MUL, and had a negative rapid
      diagnostic test result for Plasmodium falciparum histidine-rich protein 2.
      Diagnosis was confirmed by means of polymerase chain reaction. Patients were
      block randomized to AL (total target dose, 12 mg/kg for artemether and 60 mg/kg
      for lumefantrine) or CQ (25 mg/kg). The primary outcome was parasite clearance at
      24 hours in a modified intention-to-treat analysis. Results: From November 2014
      to January 2016, a total of 123 patients (including 18 children) were enrolled.
      At 24 hours after treatment 76% of patients administered AL (95% confidence
      interval [CI], 63%-86%; 44 of 58) were aparasitemic, compared with 60%
      administered CQ (47%-72%; 39 of 65; risk ratio, 1.3 [95% CI, 1.0-1.6]; P = .06).
      Overall parasite clearance was shorter after AL than after CQ (median, 18 vs 24
      hours, respectively; P = .02), with all patients aparasitemic by 48 hours. By day
      42 there were no treatment failures. The risk of anemia during follow-up was
      similar between arms. Patients treated with AL would require lower bed occupancy
      than those treated with CQ (2414 vs 2800 days per 1000 patients; incidence rate
      ratio, 0.86 [95% CI, .82-.91]; P < .001). There were no serious adverse events.
      Conclusions: AL is highly efficacious for treating uncomplicated knowlesi
      malaria; its excellent tolerability and rapid therapeutic response allow earlier
      hospital discharge, and support its use as a first-line artemisinin-combination
      treatment policy for all Plasmodium species in Malaysia. Clinical trials
      registration: NCT02001012.

PMID- 29020374
TI  - Asian dust exposure triggers acute myocardial infarction.
AB  - Aims: To elucidate whether Asian dust is associated with the incidence of acute
      myocardial infarction (AMI) and to clarify whether patients who are highly
      sensitive to Asian dust will develop AMI. Methods and results: Twenty-one
      participating institutions located throughout Kumamoto Prefecture and capable of
      performing coronary intervention were included in the study. Data for ground
      level observations of Asian dust events were measured at the Kumamoto Local
      Meteorological Observatory. Data collected between 1 April 2010 and 31 March 2015
      were analysed, and 3713 consecutive AMI patients were included. A time-stratified
      case-crossover design was applied to examine the association between Asian dust
      exposure and AMI. The occurrence of Asian dust events at 1 day before the onset
      of AMI was associated with the incidence of AMI [odds ratio (OR), 1.46; 95%
      confidence interval (CI), 1.09-1.95] and especially, non-ST-segment elevation
      myocardial infarction was significant (OR 2.03; 95% CI, 1.30-3.15). A significant
      association between AMI and Asian dust was observed in patients with age >=75
      years, male sex, hypertension, diabetes mellitus, never-smoking status, and
      chronic kidney disease (CKD). However, Asian dust events had a great impact on
      AMI onset in patients with CKD (P < 0.01). A scoring system accounting for
      several AMI risk factors was developed. The occurrence of Asian dust events was
      found to be significantly associated with AMI incidence among patients with a
      risk score of 5-6 (OR 2.45; 95% CI: 1.14-5.27). Conclusion: Asian dust events may
      lead to AMI and have a great impact on its onset in patients with CKD.

PMID- 29020376
TI  - Differences in education and premature mortality: a record linkage study of over
      35 million Italians.
AB  - Background: Large, representative studies are needed to evaluate cause-specific
      aspects of socio-economic inequalities in mortality. Methods: We conducted a
      census-based retrospective cohort study to quantify differences in cause-specific
      premature mortality by educational level in Italy. We linked the 2011 Italian
      census with 2012 and 2013 death registries. We used the mortality rate ratio
      (MRR) as a measure of relative inequality. Results: Overall, 305 043 deaths (190
      061 men-114 982 women) were registered from a population of 35 708 445 subjects
      aged 30-74. The age-standardized mortality rate for all educational levels was
      57.68 deaths per 10 000 person-years among men and 31.41 among women. MRR from
      all causes was 0.51 (95% CI: 0.49; 0.52) in men and 0.63 (95% CI: 0.61; 0.65) in
      women for the highest (university) compared to the lowest level of education
      (none or primary school). The association was stronger in single than in married
      individuals: MRRs were 0.36 (95% CI: 0.34; 0.39) in single men, 0.57 (95% CI:
      0.55; 0.59) in married men, 0.44 (95% CI: 0.40; 0.47) in single women and 0.69
      (95% CI: 0.66; 0.72) in married women. High education was associated with lower
      mortality from liver, circulatory, chronic respiratory and genitourinary diseases
      in both sexes. Highly educated men had a lower mortality from lung cancer than
      less educated men, whereas highly educated women did not have a reduced mortality
      from lung and breast cancers. Conclusion: Level of education is a strong
      indicator of premature mortality. The magnitude of the association between
      educational level and mortality differs across sexes, marital status and causes
      of death.

PMID- 29020379
TI  - Transcatheter aortic valve implantation with a mechanical-expandable device: when
      perfection is hung on a 'wire'.

PMID- 29020377
TI  - The effect of a hepatitis pay-for-performance program on outcomes of patients
      undergoing antiviral therapy.
AB  - Background: To examine the effect of a participatory pay-for-performance (P4P)
      program in Taiwan on health outcomes for patients with severe hepatitis B or C.
      Methods: This study adopted 4-year panel data from the databases of the National
      Health Insurance Administration (NHIA) in Taiwan. Using the caliper matching
      method to match patients in the P4P (experimental) group with those in the
      potential comparison group on a one-to-one basis for the year 2010, we tracked
      patients up to the year 2013 and employed Cox proportional-hazards regression
      models to evaluate the effect on patient outcomes. Results: The P4P group did not
      have a lower risk (HR = 0.44, P = 0.05) of hospital admission for severe
      hepatitis patients (i.e. need antiviral therapy). The risk of developing liver
      cirrhosis was also lower, but the reduction was not statistically significant (HR
      = 0.92, P = 0.77). Conclusions: This study found that participatory-type P4P has
      not resulted in reduced hospital admission of hepatitis B or C patients who need
      antiviral therapy. The means by which the participatory P4P program could
      strengthen patient-centered care to achieve better patient health outcomes is
      discussed in detail.

PMID- 29020380
TI  - Improving secondary cardiovascular risk prediction: taking a few steps along the
      long path from probability toward certainty.

PMID- 29020383
TI  - HDL biogenesis revisited: how desmocollin-1 could sabotage reverse cholesterol
      transport in the arterial wall.

PMID- 29020382
TI  - Moderate Alcohol Use Is Not Associated With Fibrosis Progression in Human
      Immunodeficiency Virus/Hepatitis C Virus-Coinfected Women: A Prospective Cohort
      Study.
AB  - Background: Heavy alcohol use can lead to progressive liver damage, especially in
      individuals with chronic hepatitis C (HCV); however, the impact of nonheavy use
      is not clear. We studied long-term effects of modest alcohol use on fibrosis
      progression in a large cohort of women coinfected with human immunodeficiency
      virus (HIV)/HCV. Methods: Alcohol intake was ascertained every 6 months and use
      categorized as abstinent, light (1-3 drinks/week), moderate (4-7 drinks/week),
      heavy (>7 drinks/week), and very heavy (>14 drinks/week). Fibrosis progression
      was defined as the change in Fibrosis-4 Index for Liver Fibrosis (FIB-4) units
      per year using random-intercept, random-slope mixed modeling. Results: Among 686
      HIV/HCV-coinfected women, 46.0% reported no alcohol use; 26.8% reported light
      use, 7.1% moderate use, and 19.7% heavy use (6.7% had 8-14 drinks/week and 13.0%
      had >14 drinks/week) at cohort entry. Median FIB-4 at entry was similar between
      groups. On multivariable analysis, compared to abstainers, light and moderate
      alcohol use was not associated with fibrosis progression (0.004 [95% confidence
      interval {CI}, -.11 to .12] and 0.006 [95% CI, -.18 to .19] FIB-4 units/year,
      respectively). Very heavy drinking (>14 drinks/week) showed significant fibrosis
      acceleration (0.25 [95% CI, .01-.49] FIB-4 units/year) compared to abstaining,
      whereas drinking 8-14 drinks per week showed minimal acceleration of fibrosis
      progression (0.04 [95% CI, -.19 to .28] FIB-4 units/year). Conclusions:
      Light/moderate alcohol use was not substantially associated with accelerated
      fibrosis progression, whereas drinking >14 drinks per week showed increased rates
      of fibrosis progression. Women with HIV/HCV infection should be counseled against
      heavy alcohol consumption, but complete abstinence may not be required to prevent
      accelerated liver fibrosis progression.

PMID- 29020385
TI  - A process evaluation of the 'Aware' and 'Supportive Communities' gambling harm
      minimisation programmes in New Zealand.
AB  - Background: The Gambling Act 2003 mandated a public health strategy for
      preventing and minimising gambling harm in New Zealand. Aware Communities and
      Supportive Communities are two public health programmes subsequently implemented
      nationwide. These programmes differed from common health promotion initiatives
      such as media or education campaigns as they were community-action based
      (requiring community involvement in programme planning and delivery). We carried
      out a process evaluation to determine their implementation effectiveness and
      inform improvement and future programme planning. Methods: Our qualitative
      dominant mixed methods design comprised analysis of over a hundred implementer
      progress reports (submitted July 2010 - June 2013), a staff survey and a staff
      focus group interview. Results: The programmes demonstrated capacity to not only
      achieve expected outcomes (e.g. enhanced community awareness about harmful
      gambling), but also to enhance social sustainability at the community level (e.g.
      established trustful relationships) and achieve some programme sustainability
      (e.g. community ownership over ongoing programme delivery). Conclusions: The
      evaluation noted the potential for a sustainable gambling harm-minimisation
      model. Community-action based harm-minimisation programmes offer programme
      sustainability potential which in turn offers funding cost-effectiveness when
      there are continual public health outcomes beyond initial funding. Although
      resource intensive, the community-action based approach enables culturally
      appropriate public health programmes suitable for societies where specific ethnic
      groups have higher gambling risk. Recognition of such harm-minimisation
      programmes' contribution to social sustainability is important considering the
      potential for broader public health outcomes (e.g. better life quality, lesser
      social problems) within socially sustainable societies.

PMID- 29020381
TI  - Antibody Banding Patterns of the Enzyme-Linked Immunoelectrotransfer Blot and
      Brain Imaging Findings in Patients With Neurocysticercosis.
AB  - Background: The enzyme-linked immunoelectrotransfer blot (EITB) assay is the
      reference serological test for neurocysticercosis (NCC). A positive result on
      EITB does not always correlate with the presence of active infections in the
      central nervous system (CNS), and patients with a single viable brain cyst may be
      EITB negative. Nonetheless, EITB antibody banding patterns appears to be related
      with the expression of 3 protein families of Taenia solium, and in turn with the
      characteristics of NCC in the CNS (type, stage, and burden of viable cysts).
      Methods: We evaluated EITB antibody banding patterns and brain imaging findings
      of 548 NCC cases. Similar banding patterns were grouped into homogeneous classes
      using latent class analysis. The association between classes and brain imaging
      findings was assessed. Results: Four classes were identified. Class 1 (patients
      negative or only positive to the GP50 band, related to the protein family of the
      same name) was associated with nonviable or single viable parenchymal cysticerci;
      class 2 (patients positive to bands GP42-39 and GP24, related to the T24-42
      protein family, with or without anti-GP50 antibodies) was associated with
      intraparenchymal viable and nonviable infections; classes 3 and 4 (positive to
      GP50, GP42-39, and GP24 but also responding to low molecular weight bands GP21,
      GP18, GP14, and GP13, related to the 8 kDa protein family) were associated with
      extraparenchymal and intraparenchymal multiple viable cysticerci. Conclusions:
      EITB antibody banding patterns correlate with brain imaging findings and
      complement imaging information for the diagnosis of NCC and for staging NCC
      patients.

PMID- 29020386
TI  - Seroprevalence of Antibodies to Toxocara Species in the United States and
      Associated Risk Factors, 2011-2014.
AB  - Background: Toxocariasis results from infection with larval stages of a dog and
      cat intestinal nematode and causes human morbidity. The current United States
      estimate of Toxocara exposure is 13.9% (National Health and Nutrition Examination
      Survey [NHANES] III [1988-1994]). Methods: We used a multiplex bead-based assay
      (Tc-CTL-1MBA) with purified Toxocara canis antigen to estimate Toxocara antibody
      seroprevalence in serum of 13 509 persons aged >=6 years from NHANES 2011-2014
      and identified seropositivity risk factors. We tested a subset of 500 samples
      with the T. canis enzyme immunoassay used in NHANES III to estimate prior
      seroprevalence had samples from NHANES III been tested by Tc-CTL-1MBA. Results:
      The age-standardized estimate of Toxocara seroprevalence was 5.0% (95% confidence
      interval [CI], 4.2%-5.8%), lower than previously reported even after adjusting
      for increased Tc-CTL-1MBA specificity. Risk factors for seropositivity from
      multiple logistic regression were older age, non-Hispanic black/Hispanic origin,
      male sex, living below poverty level, households with >=0.5 persons per room,
      less than college education, and birth outside of the United States. Conclusions:
      Toxocara seroprevalence estimates in 2011-2014 were lower than in a study from
      NHANES III (1988-1994), but seropositivity risk factors remained the same and
      should continue to be the focus of prevention efforts.

PMID- 29020384
TI  - Fibrosis as measured by the biomarker, tissue inhibitor metalloproteinase-1,
      predicts mortality in Age Gene Environment Susceptibility-Reykjavik (AGES
      Reykjavik) Study.
AB  - Background: Fibrosis is a key pathological process in many chronic inflammatory
      disease states. Aims: We hypothesized that tissue inhibitor metalloproteinase-1
      and matrix metalloproteinase-9 (TIMP-1 and MMP-9), biomarkers of fibrosis, would
      predict all-cause mortality and we assessed the incremental value of these
      biomarkers when adjusting for clinical and other biomarkers. Methods: The cohort
      included 5511 community-dwelling participants in the AGES-Reykjavik Study. The
      baseline Cox proportional hazards regression model was based on the Framingham
      Risk Score variables; we added TIMP-1, MMP-9, serum high-sensitivity C-reactive
      protein (hsCRP), and estimated glomerular filtration rate (eGFR). The primary
      outcome was all-cause 10-year mortality. Cause of death was categorized as
      cardiovascular death (CVD), cancer death, and other causes. Results: Participants
      averaged 76 years and 43% were male. Ten-year mortality was 41% (2263 deaths). Of
      these, 915 (16.6%) died of cardiovascular disease (CVD), 543 (9.9%) with cancer,
      and 805 (14.6%) from other causes. For 10-year mortality, age was the strongest
      predictor (log likelihood chi2 = 798.7, P < 0.0001), followed by TIMP-1 (chi2 =
      125.2, P < 0.0001), female gender, current smoker, diabetes mellitus, total
      cholesterol, eGFR (chi2 16.7, P < 0.0001), body mass index, and hsCRP (chi2 11.3,
      P = 0.0008) in that order. TIMP-1 and hsCRP had the highest continuous net
      reclassification improvement over the baseline model for 5-year survival [net
      reclassification index (NRI) 0.28 and 0.19, respectively, both P < 0.0001] and
      for 10-year survival (NRI 0.19 and 0.11, respectively, both statistically
      significant). Conclusion: TIMP-1 is the strongest predictor of all-cause
      mortality after age. The metabolic pathways regulating extracellular matrix
      homeostasis and fibrogenic processes appear pathologically relevant and are
      prognostically important.

PMID- 29020388
TI  - Temporal trends in atrial fibrillation recurrence rates after ablation between
      2005 and 2014: a nationwide Danish cohort study.
AB  - Aims: During the last decade, ablation has increasingly been used in rhythm
      control management of patients with atrial fibrillation (AF). Over time,
      experience and techniques have improved and indications for ablation have
      expanded. The purpose of this study was to investigate whether the recurrence
      rate of AF following ablation has improved during last decade. Methods and
      results: Through Danish nationwide registers, all patients with first-time AF
      ablation, between 2005 and 2014 in Denmark were identified. Recurrent AF after
      ablation was identified with 1 year follow-up. A total of 5425 patients
      undergoing first-time ablation were included. While patient median age increased
      over time the median AF duration prior to ablation decreased. The rates of
      recurrent AF decreased from 45% in 2005-2006 to 31% 2013-2014 with the relative
      risk of recurrent AF almost halved with an odds ratio of 0.57 [95% confidence
      intervals (95% CI) 0.47-0.68] in 2013-2014 compared with patients undergoing
      ablation in 2005-2006. Female gender, hypertension, AF duration >2 years, and
      cardioversion within 1 year prior to ablation were all associated with an
      increased risk of recurrent AF. Conclusion: One year risk of recurrent AF
      following first-time ablation has almost halved from 2006 to 2014. Hypertension,
      female sex, cardioversion 1 year prior to ablation, and AF duration for more than
      2 years all increased the associated risk of recurrent AF.

PMID- 29020389
TI  - Cactus aorta.

PMID- 29020392
TI  - How to use Mendelian randomization to anticipate the results of randomized
      trials.

PMID- 29020390
TI  - Smoking may increase the risk of influenza hospitalization and reduce influenza
      vaccine effectiveness in the elderly.
AB  - Background: Through its effects on the immune system, smoking may facilitate
      influenza virus infection, its severity and its most frequent complications. The
      objective was to investigate the smoking history as a risk factor for influenza
      hospitalization and influenza vaccine effectiveness in elderly smokers/ex-smokers
      and non-smokers. Methods: We carried out a multicenter case-control study in the
      2013-2014 and 2014-2015 influenza seasons. Cases aged >=65 years and age-, sex
      matched controls were selected from 20 Spanish hospitals. We collected
      epidemiological variables, comorbidities, vaccination history and the smoking
      history. The risk of hospitalization due to smoking (current smokers and ex
      smokers) was determined using the adjusted odds ratio (aOR) with conditional
      logistic regression models. Vaccine effectiveness (VE) was calculated using the
      formula: VE = (1 - aOR) * 100. Results: We studied 728 cases and 1826 controls.
      Cases had a higher frequency of smoking (47.4% vs 42.1%). Smoking was associated
      with an increased risk of influenza hospitalization (aOR = 1.32, 95% CI: 1.04
      1.68). Influenza vaccine effectiveness in preventing hospitalization was 21% (95%
      CI: -2 to 39) in current/ex-smokers and 39% in non-smokers (95% CI: 22-52).
      Conclusions: A history of smoking may increase the risk of hospitalization in
      smokers and ex-smokers. Preventing smoking could reduce hospitalizations due to
      influenza. Smokers and ex-smokers should be informed of the risk of
      hospitalization due to influenza infection, and encouraged to stop smoking.
      Smokers should be considered an at-risk group to be aggressively targeted for
      routine influenza vaccination.

PMID- 29020387
TI  - Reversal of Stress-Induced Social Interaction Deficits by Buprenorphine.
AB  - Background: Patients with post-traumatic stress disorder frequently report
      persistent problems with social interactions, emerging after a traumatic
      experience. Chronic social defeat stress is a widely used rodent model of stress
      that produces robust and sustained social avoidance behavior. The avoidance of
      other rodents can be reversed by 28 days of treatment with selective serotonin
      reuptake inhibitors, the only pharmaceutical class approved by the U.S. Food and
      Drug Administration for treating post-traumatic stress disorder. In this study,
      the sensitivity of social interaction deficits evoked by 10 days of chronic
      social defeat stress to prospective treatments for post-traumatic stress disorder
      was examined. Methods: The effects of acute and repeated treatment with a low
      dose of buprenorphine (0.25 mg/kg/d) on social interaction deficits in male
      C57BL/6 mice by chronic social defeat stress were studied. Another cohort of mice
      was used to determine the effects of the selective serotonin reuptake inhibitor
      fluoxetine (10 mg/kg/d), the NMDA antagonist ketamine (10 mg/kg/d), and the
      selective kappa opioid receptor antagonist CERC-501 (1 mg/kg/d). Changes in mRNA
      expression of Oprm1 and Oprk1 were assessed in a separate cohort. Results:
      Buprenorphine significantly reversed social interaction deficits produced by
      chronic social defeat stress following 7 days of administration, but not after
      acute injection. Treatment with fluoxetine for 7 days, but not 24 hours, also
      reinstated social interaction behavior in mice that were susceptible to chronic
      social defeat. In contrast, CERC-501 and ketamine failed to reverse social
      avoidance. Gene expression analysis found: (1) Oprm1 mRNA expression was reduced
      in the hippocampus and increased in the frontal cortex of susceptible mice and
      (2) Oprk1 mRNA expression was reduced in the amygdala and increased in the
      frontal cortex of susceptible mice compared to non-stressed controls and stress
      resilient mice. Conclusions: Short-term treatment with buprenorphine and
      fluoxetine normalized social interaction after chronic social defeat stress. In
      concert with the changes in opioid receptor expression produced by chronic social
      defeat stress, we speculate that buprenorphine's efficacy in this model of post
      traumatic stress disorder may be associated with the ability of this compound to
      engage multiple opioid receptors.

PMID- 29020393
TI  - Making sense of a seemingly odd connection.

PMID- 29020394
TI  - Patients With Isolated Hepatitis B Core Antibody: Has the Time Come to Vaccinate?

PMID- 29020395
TI  - Insight Into the Complex Epidemiology of Multidrug-Resistant Enterobacteriaceae.

PMID- 29020391
TI  - Association between mitochondrial DNA copy number and sudden cardiac death:
      findings from the Atherosclerosis Risk in Communities study (ARIC).
AB  - Aims: Sudden cardiac death (SCD) is a major public health burden. Mitochondrial
      dysfunction has been implicated in a wide range of cardiovascular diseases
      including cardiomyopathy, heart failure, and arrhythmias, but it is unknown if it
      also contributes to SCD risk. We sought to examine the prospective association
      between mtDNA copy number (mtDNA-CN), a surrogate marker of mitochondrial
      function, and SCD risk. Methods and results: We measured baseline mtDNA-CN in 11
      093 participants from the Atherosclerosis Risk in Communities (ARIC) study. mtDNA
      copy number was calculated from probe intensities of mitochondrial single
      nucleotide polymorphisms (SNP) on the Affymetrix Genome-Wide Human SNP Array 6.0.
      Sudden cardiac death was defined as a sudden pulseless condition presumed due to
      a ventricular tachyarrhythmia in a previously stable individual without evidence
      of a non-cardiac cause of cardiac arrest. Sudden cardiac death cases were
      reviewed and adjudicated by an expert committee. During a median follow-up of
      20.4 years, we observed 361 SCD cases. After adjusting for age, race, sex, and
      centre, the hazard ratio for SCD comparing the 1st to the 5th quintiles of mtDNA
      CN was 2.24 (95% confidence interval 1.58-3.19; P-trend <0.001). When further
      adjusting for traditional cardiovascular disease risk factors, prevalent coronary
      heart disease, heart rate, QT interval, and QRS duration, the association
      remained statistically significant. Spline regression models showed that the
      association was approximately linear over the range of mtDNA-CN values. No
      apparent interaction by race or by sex was detected. Conclusion: In this
      community-based prospective study, mtDNA-CN in peripheral blood was inversely
      associated with the risk of SCD.

PMID- 29020396
TI  - Perception and use of Pap smear screening among rural and urban women in Romania.
AB  - Background: In 2012 the National Screening Program for all women between 25 and
      64 years of age was launched in Romania. Public awareness is an important factor
      in the success of a screening program. For this reason, we intended to assess the
      perception and the level of awareness of Romanian women regarding the Pap test in
      the prevention of cervical cancer. Methods: A cross-sectional study was conducted
      among 454 women from rural and urban areas. For our study, we used a
      questionnaire covering general characteristics, awareness, knowledge and
      practices regarding cervical cancer and Pap smear. Results: 431 participants
      (95%) had heard of cervical cancer and Pap smear but only 71.8% knew the exact
      role of it. Bivariate analysis showed that knowledge about the importance of the
      Pap smear, early detection and treatment of early-stage cervical cancer was
      reduced among women with low socio-economic status, mainly living in rural area.
      The most frequent reasons for avoiding Pap smear screening were: lack of money,
      embarrassment or fear of gynaecological consultation and pain, the feeling that
      they don't need it, misconceptions about cervical cancer, fatalistic attitude,
      perceived low susceptibility to cervical cancer. Conclusions: Because the uptake
      and the success of cervical cancer screening are determined by women's knowledge
      and awareness of Pap smear, it is critical to improve these perceptions in the
      near future especially in rural area characterized by a low socio-economic
      status.

PMID- 29020397
TI  - Pentraxin 3 Gene Polymorphisms and Pulmonary Aspergillosis in Chronic Obstructive
      Pulmonary Disease Patients.
AB  - Background: Pentraxin 3 (PTX3) plays an important role in resistance to
      Aspergillus infections. Previous studies have suggested that PTX3 polymorphisms
      influence the risk of invasive aspergillosis among transplantation recipients.
      This study investigated the association between PTX3 gene polymorphisms and
      pulmonary aspergillosis in a chronic obstructive pulmonary disease (COPD)
      population. Methods: We included 173 consecutive inpatients with COPD. Thirty-six
      case patients were finally diagnosed with pulmonary aspergillosis. Among these,
      25 case patients had invasive pulmonary aspergillosis (IPA), and 11 case patients
      had chronic pulmonary aspergillosis (CPA). Three single nucleotide polymorphisms
      (SNPs; rs2305619, rs3816527, and rs1840680) in the PTX3 gene were detected by
      polymerase chain reaction direct sequencing, and their associations with
      aspergillosis were evaluated. Plasma PTX3 levels were measured by enzyme-linked
      immunosorbent assay. Results: Three SNPs were consistent with Hardy-Weinberg
      equilibrium. The recessive model for SNP rs1840680 suggests that the AA
      homozygote is associated with a higher risk for pulmonary aspergillosis (both IPA
      and CPA) in COPD patients. However, for genotypic and allele frequencies of
      rs2305619 and rs3816527, no association was observed. The distribution of
      haplotypes (rs2305619 and rs3816527) also showed no significant differences.
      Plasma PTX3 levels significantly increased in IPA patients. In the IPA group, the
      rs1840680 AA genotype subjects showed lower plasma PTX3 levels than those
      harboring AG and GG genotypes. Conclusions: This study showed a significant
      association between PTX3 rs1840680 polymorphisms and the susceptibility of
      pulmonary aspergillosis in patients with COPD. Plasma PTX3 levels may be
      potentially used as indicators for the diagnosis of IPA in COPD patients.

PMID- 29020398
TI  - Predicting the future by looking at the past: necessary but not binding.

PMID- 29020400
TI  - Assessing the quality of health technology registers for national guidance
      development.
AB  - Background: The National Institute of Health and Care Excellence makes use of
      registers to collect data for technologies that require more evidence to inform
      future decision-making. This is particularly so for the Interventional Procedures
      Programme, which since 2003 has produced guidance for procedures that are
      typically not well established, meaning that named registers are often
      recommended for future data collection. Methods: We constructed a questionnaire
      based on quality standards for recommended registers defined by the
      Interventional Procedures Programme. All guidance from 2003 to 2016 were reviewed
      to identify recommended registers and compile a list of corresponding registries.
      We made a maximum of four attempts to contact each registry. Each register was
      scored on seven quality standards: accessibility, responsiveness, data
      publication, data coverage, data validity, independent oversight and data
      protection, with a maximum of 14 points. Results: We obtained responses from 17
      out of 24 eligible registries, a response rate of 70.8%. The mean total score was
      8.5 (standard deviation 2.9, range 4-14). Overall, the quality of recommended
      registers was disappointing, with a split between large registries that scored
      highly across all standards and smaller registries that scored poorly.
      Conclusions: This the first study to our knowledge to assess the quality of
      registers recommended by health technology assessment agencies. Only a limited
      number of registers were mature enough to deliver evidence of sufficiently high
      quality to inform funding decisions. A standardised quality assessment tool is
      needed to evaluate registers before their recommendation for observational data
      gathering by decision-making bodies.

PMID- 29020399
TI  - International variations in the gestational age distribution of births: an
      ecological study in 34 high-income countries.
AB  - Background: Few studies have investigated international variations in the
      gestational age (GA) distribution of births. While preterm births (22-36 weeks
      GA) and early term births (37-38 weeks) are at greater risk of adverse health
      outcomes compared to full term births (39-40 weeks), it is not known if countries
      with high preterm birth rates also have high early term birth rates. We examined
      rate associations between preterm and early term births and mean term GA by mode
      of delivery onset. Methods: We used routine aggregate data on the GA distribution
      of singleton live births from up to 34 high-income countries/regions in 1996,
      2000, 2004, 2008 and 2010 to study preterm and early term births overall and by
      spontaneous or indicated onset. Pearson correlation coefficients were adjusted
      for clustering in time trend analyses. Results: Preterm and early term births
      ranged from 4.1% to 8.2% (median 5.5%) and 15.6% to 30.8% (median 22.2%) of live
      births in 2010, respectively. Countries with higher preterm birth rates in 2004
      2010 had higher early term birth rates (r > 0.50, P < 0.01) and changes over time
      were strongly correlated overall (adjusted-r = 0.55, P < 0.01) and by mode of
      onset. Conclusion: Positive associations between preterm and early term birth
      rates suggest that common risk factors could underpin shifts in the GA
      distribution. Targeting modifiable population risk factors for delivery before 39
      weeks GA may provide a useful preterm birth prevention paradigm.

PMID- 29020401
TI  - Discrimination of patients with type 2 myocardial infarction.
AB  - Aims: The differentiation of type 1 and type 2 myocardial infarction (T1MI, T2MI)
      is important, but challenging in the emergency department. We aimed to
      investigate the clinical characteristics and cardiovascular outcome of T2MI
      patients and to develop a clinical decision tool to differentiate T1MI and T2MI
      patients. Methods and results: We prospectively enrolled 1548 patients with
      suspected MI. All patients were followed for up to 2 years to assess mortality.
      We used logistic regression with backward step-down selection to determine the
      most important predictors of T2MI. Based on these regression coefficients, we
      developed a diagnostic prediction model (score) to diagnose T2MI. T2MI was the
      final diagnosis of 99 patients. Patients with T2MI showed a high 1-year mortality
      rate (13.8%), which equals that of T1MI patients (9.4%). Female sex (Beta 1.27
      [95% confidence interval; CI 0.67-1.90]), not having radiating chest pain (Beta
      1.62 [CI 0.96-2.34]) and a baseline high-sensitivity troponin I concentration <=
      40.8 ng/L (Beta 1.30 [CI 0.74-1.89]) were the strongest predictors for T2MI.
      Their combination resulted in an area under the curve of 0.71 to discriminate
      T1MI and T2MI. The binary score based on this model assigns one point to each of
      the predictors. Patients with the highest score value of 3 had a 72% probability
      of T2MI. Conclusion: T2MI patients are a heterogeneous population with high
      cardiovascular risk. A score based on laboratory and clinical parameters might
      help to differentiate T1MI and T2MI patients. The additional use of this score in
      clinical routine needs to be investigated prospectively. Trial registration:
      www.clinicaltrials.gov (NCT02355457).

PMID- 29020402
TI  - Women with hypertrophic cardiomyopathy have worse survival.
AB  - Aims: Sex differences in hypertrophic cardiomyopathy (HCM) remain unclear. We
      sought to characterize sex differences in a large HCM referral centre population.
      Methods and results: Three thousand six hundred and seventy-three adult patients
      with HCM underwent evaluation between January 1975 and September 2012 with 1661
      (45.2%) female. Kaplan-Meier survival curves were assessed via log-rank test. Cox
      proportional hazard regression analyses evaluated the relation of sex with
      survival. At index visit, women were older (59 +/- 16 vs. 52 +/- 15 years, P <
      0.0001) had more symptoms [New York Heart Association (NYHA) Class III-IV 45.0%
      vs. 35.3%, P < 0.0001], more obstructive physiology (77.4% vs. 71.8%, P =
      0.0001), more mitral regurgitation (moderate or greater in 56.1% vs. 43.9%, P <
      0.0001), higher E/e' ratio (n = 1649, 20.6 vs. 15.6, P < 0.0001), higher
      estimated pulmonary artery systolic pressure (n = 1783, 40.8 +/- 15.4 vs. 34.8 +/
      10.8 mmHg, P < 0.0001), worse cardiopulmonary exercise performance (n = 1267;
      percent VO2 predicted 62.8 +/- 20% vs. 65.8 +/- 19.2%, P = 0.007), and underwent
      more frequent alcohol septal ablation (4.9% vs. 3.0%, P = 0.004) but similar
      frequency of myectomy (28% vs. 30%, P = 0.24). Median follow-up was 10.9 (IQR 7.4
      16.2) years. Kaplan-Meier analysis demonstrated lower survival in women compared
      with men (P < 0.0001). In multivariable modelling, female sex remained
      independently associated with mortality (HR 1.13 [1.03-1.22], P = 0.01) when
      adjusted for age, NYHA Class III-IV symptoms, and cardiovascular comorbidities.
      Conclusion: Women with HCM present at more advanced age, with more symptoms,
      worse cardiopulmonary exercise tolerance, and different haemodynamics than men.
      Sex is an important determinant in HCM management as women with HCM have worse
      survival. Women may require more aggressive diagnostic and therapeutic
      approaches.

PMID- 29020403
TI  - Cardiac and systemic rejuvenation after cardiosphere-derived cell therapy in
      senescent rats.
AB  - Aim: The aim is to assess the effects of CDCs on heart structure, function, gene
      expression, and systemic parameters in aged rats. Diastolic dysfunction is
      characteristic of aged hearts. Cardiosphere-derived cell (CDC) therapy has
      exhibited several favourable effects on heart structure and function in humans
      and in preclinical models; however, the effects of CDCs on aging have not been
      evaluated. Methods and Results: We compared intra-cardiac injections of neonatal
      rat CDCs to vehicle (phosphate-buffered saline, PBS) in 21.8 +/- 1.6 month-old
      rats (mean +/- standard deviation; n = 23 total). Ten rats 4.1 +/- 1.5 months of
      age comprised a young reference group. Blood, echocardiographic, haemodynamic and
      treadmill stress tests were performed at baseline in all animals, and 1 month
      after treatment in old animals. Histology and the transcriptome were assessed
      after terminal phenotyping. For in vitro studies, human heart progenitors from
      older donors, or cardiomyocytes from aged rats were exposed to human CDCs or
      exosomes secreted by CDCs (CDC-XO) from paediatric donors. Transcriptomic
      analysis revealed that CDCs, but not PBS, recapitulated a youthful pattern of
      gene expression in the hearts of old animals (85.5% of genes differentially
      expressed, P < 0.05). Telomeres in heart cells were longer in CDC-transplanted
      animals (P < 0.0001 vs. PBS). Cardiosphere-derived cells attenuated hypertrophy
      by echo (P < 0.01); histology confirmed decreases in cardiomyocyte area (P <
      0.0001) and myocardial fibrosis (P < 0.05) vs. PBS. Cardiosphere-derived cell
      injection improved diastolic dysfunction [lower E/A (P < 0.01), E/E' (P = 0.05),
      end-diastolic pressure-volume relationship (P < 0.05) compared with baseline),
      and lowered serum brain natriuretic peptide (both P < 0.05 vs. PBS). In CDC
      transplanted old rats, exercise capacity increased ~20% (P < 0.05 vs. baseline),
      body weight decreased ~30% less (P = 0.05 vs. PBS) and hair regrowth after
      shaving was more robust (P < 0.05 vs. PBS). Serum biomarkers of inflammation (IL
      10, IL-1b, and IL-6) improved in the CDC group (P < 0.05 for each, all vs. PBS).
      Young CDCs secrete exosomes which increase telomerase activity, elongate telomere
      length, and reduce the number of senescent human heart cells in culture.
      Conclusion: Young CDCs rejuvenate old animals as gauged by cardiac gene
      expression, heart function, exercise capacity, and systemic biomarkers.

PMID- 29020404
TI  - Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to
      Carbapenem-Resistant Enterobacteriaceae.
AB  - Background: The efficacy of ceftazidime-avibactam-a cephalosporin-beta-lactamase
      inhibitor combination with in vitro activity against Klebsiella pneumoniae
      carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CRE)-compared
      with colistin remains unknown. Methods: Patients initially treated with either
      ceftazidime-avibactam or colistin for CRE infections were selected from the
      Consortium on Resistance Against Carbapenems in Klebsiella and other
      Enterobacteriaceae (CRACKLE), a prospective, multicenter, observational study.
      Efficacy, safety, and benefit-risk analyses were performed using intent-to-treat
      analyses with partial credit and the desirability of outcome ranking approaches.
      The ordinal efficacy outcome was based on disposition at day 30 after starting
      treatment (home vs not home but not observed to die in the hospital vs hospital
      death). All analyses were adjusted for confounding using inverse probability of
      treatment weighting (IPTW). Results: Thirty-eight patients were treated first
      with ceftazidime-avibactam and 99 with colistin. Most patients received
      additional anti-CRE agents as part of their treatment. Bloodstream (n = 63; 46%)
      and respiratory (n = 30; 22%) infections were most common. In patients treated
      with ceftazidime-avibactam versus colistin, IPTW-adjusted all-cause hospital
      mortality 30 days after starting treatment was 9% versus 32%, respectively
      (difference, 23%; 95% bootstrap confidence interval, 9%-35%; P = .001). In an
      analysis of disposition at 30 days, patients treated with ceftazidime-avibactam,
      compared with those treated within colistin, had an IPTW-adjusted probability of
      a better outcome of 64% (95% confidence interval, 57%-71%). Partial credit
      analyses indicated uniform superiority of ceftazidime-avibactam to colistin.
      Conclusions: Ceftazidime-avibactam may be a reasonable alternative to colistin in
      the treatment of K. pneumoniae carbapenemase-producing CRE infections. These
      findings require confirmation in a randomized controlled trial.

PMID- 29020407
TI  - Does obesity along with major depression or anxiety lead to higher use of health
      care and costs? A 6-year follow-up study.
AB  - Background: Evidence lacks on whether obesity along with major depression
      (MD)/anxiety leads to higher health care use (HCU) and health care-related costs
      (HCC) compared with either condition alone. The objective of the study was to
      examine the longitudinal associations of obesity, MD/anxiety, and their
      combination with HCU and HCC. Methods: Longitudinal data (2004-2013) among N =
      2706 persons at baseline and 2-,4-, and 6-year follow-up were collected on
      obesity, MD/anxiety and HCU. Results: The combination of obesity and MD/anxiety
      was associated with an increased risk of primary and specialty care visits, and
      of hospitalizations, odds ratios (95%-confidence intervals): 1.83 (1.44; 2.34),
      1.31 (1.06; 1.61) and 1.79 (1.40; 2.29) compared to non-obese and non-depressed
      individuals. The primary and specialty care costs were higher in persons with
      obesity and MD/anxiety than in persons without these conditions, but the relative
      excess risk due to interactions between obesity and MD/anxiety regarding HCU and
      HCC were not statistically significant (i.e. no synergistic effect). Conclusions:
      Obesity along with MD/anxiety leads to higher HCU and HCC over time. However, the
      HCC associated with the joint presence of both conditions are not higher than the
      sum of the HCC due to each condition independently.

PMID- 29020408
TI  - Identifying patients with acute total coronary occlusion in NSTEACS: finding the
      high-risk needle in the haystack.

PMID- 29020405
TI  - Neuroticism Associates with Cerebral in Vivo Serotonin Transporter Binding
      Differently in Males and Females.
AB  - Background: Neuroticism is a major risk factor for affective disorders. This
      personality trait has been hypothesized to associate with synaptic availability
      of the serotonin transporter, which critically controls serotonergic tone in the
      brain. However, earlier studies linking neuroticism and serotonin transporter
      have failed to produce converging findings. Because sex affects both the
      serotonergic system and the risk that neuroticism poses to the individual, sex
      may modify the association between neuroticism and serotonin transporter, but
      this question has not been investigated by previous studies. Methods: Here, we
      combined data from 4 different positron emission tomography imaging centers to
      address whether neuroticism is related to serotonin transporter binding in vivo.
      The data set included serotonin transporter binding potential values from the
      thalamus and striatum and personality scores from 91 healthy males and 56 healthy
      females. We specifically tested if the association between neuroticism and
      serotonin transporter is different in females and males. Results: We found that
      neuroticism and thalamic serotonin transporter binding potentials were associated
      in both males and females, but with opposite directionality. Higher neuroticism
      associated with higher serotonin transporter binding potential in males
      (standardized beta 0.292, P=.008), whereas in females, higher neuroticism
      associated with lower serotonin transporter binding potential (standardized beta 
      0.288, P=.014). Conclusions: The finding is in agreement with recent studies
      showing that the serotonergic system is involved in affective disorders
      differently in males and females and suggests that contribution of thalamic
      serotonin transporter to the risk of affective disorders depends on sex.

PMID- 29020406
TI  - New insights into mitral valve dystrophy: a Filamin-A genotype-phenotype and
      outcome study.
AB  - Aims: Filamin-A (FLNA) was identified as the first gene of non-syndromic mitral
      valve dystrophy (FLNA-MVD). We aimed to assess the phenotype of FLNA-MVD and its
      impact on prognosis. Methods and results: We investigated the disease in 246
      subjects (72 mutated) from four FLNA-MVD families harbouring three different FLNA
      mutations. Phenotype was characterized by a comprehensive echocardiography
      focusing on mitral valve apparatus in comparison with control relatives. In this
      X-linked disease valves lesions were severe in men and moderate in women. Most
      men had classical features of mitral valve prolapse (MVP), but without chordal
      rupture. By contrast to regular MVP, mitral leaflet motion was clearly restricted
      in diastole and papillary muscles position was closer to mitral annulus. Valvular
      abnormalities were similar in the four families, in adults and young patients
      from early childhood suggestive of a developmental disease. In addition, mitral
      valve lesions worsened over time as encountered in degenerative conditions.
      Polyvalvular involvement was frequent in males and non-diagnostic forms frequent
      in females. Overall survival was moderately impaired in men (P = 0.011). Cardiac
      surgery rate (mainly valvular) was increased (33.3 +/- 9.8 vs. 5.0 +/- 4.9%, P <
      0.0001; hazard ratio 10.5 [95% confidence interval: 2.9-37.9]) owing mainly to a
      lifetime increased risk in men (76.8 +/- 14.1 vs. 9.1 +/- 8.7%, P < 0.0001).
      Conclusion: FLNA-MVD is a developmental and degenerative disease with complex
      phenotypic expression which can influence patient management. FLNA-MVD has unique
      features with both MVP and paradoxical restricted motion in diastole, sub
      valvular mitral apparatus impairment and polyvalvular lesions in males. FLNA-MVD
      conveys a substantial lifetime risk of valve surgery in men.

PMID- 29020409
TI  - Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk
      biomarker: a systematic review and dose-response meta-analysis.
AB  - Aims: Gut microbiota-derived metabolite trimethylamine-N-oxide (TMAO) is emerging
      as a new potentially important cause of increased cardiovascular risk. The
      purpose of this meta-analysis was to systematically estimate and quantify the
      association between TMAO plasma levels, mortality, and major adverse cardio and
      cerebrovascular events (MACCE). Methods and results: MEDLINE, ISI Web of Science,
      and SCOPUS databases were searched for ad hoc studies published up to April 2017.
      Associations between TMAO plasma levels, all-cause mortality (primary outcome)
      and MACCE (secondary outcome) were systematically addressed. A total of 17
      clinical studies were included in the analytic synthesis, enrolling 26 167
      subjects. The mean follow-up in our study population was 4.3 +/- 1.5 years. High
      TMAO plasma levels were associated with increased incidence of all-cause
      mortality [14 studies for 16 cohorts enrolling 15 662 subjects, hazard ratio
      (HR): 1.91; 95% confidence interval (CI): 1.40-2.61, P < 0.0001, I2 = 94%] and
      MACCE (5 studies for 6 cohorts enrolling 13 944 subjects, HR: 1.67, 95% CI: 1.33
      2.11, P < 0.00001, I2 = 46%,). Dose-response meta-analysis revealed that the
      relative risk (RR) for all-cause mortality increased by 7.6% per each 10 MUmol/L
      increment of TMAO [summary RR: 1.07, 95% CI (1.04-1.11), P < 0.0001; based on
      seven studies]. Association of TMAO and mortality persisted in all examined
      subgroups and across all subject populations. Conclusions: This is the first
      systematic review and meta-analysis demonstrating the positive dose-dependent
      association between TMAO plasma levels and increased cardiovascular risk and
      mortality.

PMID- 29020411
TI  - Reduction of low density lipoprotein-cholesterol and cardiovascular events with
      proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors and statins: an
      analysis of FOURIER, SPIRE, and the Cholesterol Treatment Trialists
      Collaboration.

PMID- 29020410
TI  - The Requirement of L-Type Voltage-Dependent Calcium Channel (L-VDCC) in the Rapid
      Acting Antidepressant-Like Effects of Scopolamine in Mice.
AB  - Background: Previous studies have shown that a low dose of scopolamine produces
      rapid-acting antidepressant-like actions in rodents. Understanding the mechanisms
      underlying this effect and the dose-dependent variations of drug responses
      remains an important task. L-type voltage-dependent calcium channels were found
      to mediate rapid-acting antidepressant effects of certain medications (e.g.,
      ketamine). Therefore, it is of great interest to determine the involvement of L
      type voltage-dependent calcium channels in the action of scopolamine. Methods:
      Herein, we investigated the mechanisms underlying behavioral responses to various
      doses of scopolamine in mice to clarify the involvement of L-type voltage
      dependent calcium channels in its modes of action. Open field test, novel object
      recognition test, and forced swimming test were performed on mice administered
      varied doses of scopolamine (0.025, 0.05, 0.1, 1, and 3 mg/kg, i.p.) alone or
      combined with L-type voltage-dependent calcium channel blocker verapamil (5
      mg/kg, i.p.). Then, the changes in brain-derived neurotrophic factor and
      neuropeptide VGF (nonacronymic) levels in the hippocampus and prefrontal cortex
      of these mice were analyzed. Results: Low doses of scopolamine (0.025 and 0.05
      mg/kg) produced significant antidepressant-like effects in the forced swimming
      test, while higher doses (1 and 3 mg/kg) resulted in significant memory deficits
      and depressive-like behaviors. Moreover, the behavioral changes in responses to
      various doses may be related to the upregulation (0.025 and 0.05 mg/kg) and
      downregulation (1 and 3 mg/kg) of brain-derived neurotrophic factor and VGF in
      the hippocampus and prefrontal cortex in mice. We further found that the rapid
      acting antidepressant-like effects and the upregulation on brain-derived
      neurotrophic factor and VGF produced by a low dose of scopolamine (0.025 mg/kg)
      were completely blocked by verapamil. Conclusions: These results indicate that L
      type voltage-dependent calcium channels are likely involved in the behavioral
      changes in response to various doses of scopolamine through the regulation of
      brain-derived neurotrophic factor and VGF levels.

PMID- 29020412
TI  - Emerging Role of One-Carbon Metabolism and DNA Methylation Enrichment on delta
      Containing GABAA Receptor Expression in the Cerebellum of Subjects with Alcohol
      Use Disorders (AUD).
AB  - Background: Cerebellum is an area of the brain particularly sensitive to the
      effects of acute and chronic alcohol consumption. Alcohol exposure decreases
      cerebellar Purkinje cell output by increasing GABA release from Golgi cells onto
      extrasynaptic alpha6/delta-containing GABAA receptors located on glutamatergic
      granule cells. Here, we studied whether chronic alcohol consumption induces
      changes in GABAA receptor subunit expression and whether these changes are
      associated with alterations in epigenetic mechanisms via DNA methylation.
      Methods: We used a cohort of postmortem cerebellum from control and chronic
      alcoholics, here defined as alcohol use disorders subjects (n=25/group). S
      adenosyl-methionine/S-adenosyl-homocysteine were measured by high-performance
      liquid chromatography. mRNA levels of various genes were assessed by reverse
      transcriptase-quantitative polymerase chain reaction. Promoter methylation
      enrichment was assessed using methylated DNA immunoprecipitation and hydroxy
      methylated DNA immunoprecipitation assays. Results: mRNAs encoding key enzymes of
      1-carbon metabolism that determine the S-adenosyl-methionine/S-adenosyl
      homocysteine ratio were increased, indicating higher "methylation index" in
      alcohol use disorder subjects. We found that increased methylation of the
      promoter of the delta subunit GABAA receptor was associated with reduced mRNA and
      protein levels in the cerebellum of alcohol use disorder subjects. No changes
      were observed in alpha1- or alpha6-containing GABAA receptor subunits. The
      expression of DNA-methyltransferases (1, 3A, and 3B) was unaltered, whereas the
      mRNA level of TET1, which participates in the DNA demethylation pathway, was
      decreased. Hence, increased methylation of the delta subunit GABAA receptor
      promoter may result from alcohol-induced reduction of DNA demethylation.
      Conclusion: Together, these results support the hypothesis that aberrant DNA
      methylation pathways may be involved in cerebellar pathophysiology of alcoholism.
      Furthermore, this work provides novel evidence for a central role of DNA
      methylation mechanisms in the alcohol-induced neuroadaptive changes of human
      cerebellar GABAA receptor function.

PMID- 29020413
TI  - Incidence, predictors, and clinical outcomes of coronary obstruction following
      transcatheter aortic valve replacement for degenerative bioprosthetic surgical
      valves: insights from the VIVID registry.
AB  - Aims: There are limited data on coronary obstruction following transcatheter
      valve-in-valve (ViV) implantation inside failed aortic bioprostheses. The
      objectives of this study were to determine the incidence, predictors, and
      clinical outcomes of coronary obstruction in transcatheter ViV procedures.
      Methods and results: A total of 1612 aortic procedures from the Valve-in-Valve
      International Data (VIVID) Registry were evaluated. Data were subject to
      centralized blinded corelab computed tomography (CT) analysis in a subset of
      patients. The virtual transcatheter valve to coronary ostium distance (VTC) was
      determined. A total of 37 patients (2.3%) had clinically evident coronary
      obstruction. Baseline clinical characteristics in the coronary obstruction
      patients were similar to controls. Coronary obstruction was more common in
      stented bioprostheses with externally mounted leaflets or stentless bioprostheses
      than in stented with internally mounted leaflets bioprostheses (6.1% vs. 3.7% vs.
      0.8%, respectively; P < 0.001). CT measurements were obtained in 20 (54%) and 90
      (5.4%) of patients with and without coronary obstruction, respectively. VTC
      distance was shorter in coronary obstruction patients in relation to controls
      (3.24 +/- 2.22 vs. 6.30 +/- 2.34, respectively; P < 0.001). Using multivariable
      analysis, the use of a stentless or stented bioprosthesis with externally mounted
      leaflets [odds ratio (OR): 7.67; 95% confidence interval (CI): 3.14-18.7; P <
      0.001] associated with coronary obstruction for the global population. In a
      second model with CT data, a shorter VTC distance predicted this complication
      (OR: 0.22 per 1 mm increase; 95% CI: 0.09-0.51; P < 0.001), with an optimal cut
      off level of 4 mm (area under the curve: 0.943; P < 0.001). Coronary obstruction
      was associated with a high 30-day mortality (52.9% vs. 3.9% in the controls,
      respectively; P < 0.001). Conclusion: Coronary obstruction following aortic ViV
      procedures is a life-threatening complication that occurred more frequently in
      patients with prior stentless or stented bioprostheses with externally mounted
      leaflets and in those with a short VTC.

PMID- 29020415
TI  - Coronary obstruction: a rare but devastating complication during transcatheter
      aortic valve-in-valve implantation.

PMID- 29020417
TI  - The Reducer device in patients with angina pectoris: mechanisms, indications, and
      perspectives.
AB  - Despite available pharmacological and interventional therapies, refractory angina
      is a common and disabling clinical condition, and a major public health problem,
      which affects patients' quality-of-life, and has a significant impact upon health
      care resources. Persistent angina is common not only in patients who are not good
      candidates for revascularization, but also in patients following successful
      revascularization. Clearly, there is a need for additional treatment options for
      refractory angina beyond currently available pharmacological and interventional
      therapies. It is of pivotal importance, in this condition, to practice a patient
      centred health assessment approach, measuring success of a new therapy by its
      effects on patients' symptoms, functional status, and quality-of-life, rather
      than hard clinical endpoints as used in clinical studies. The coronary sinus
      Reducer is a novel technology designed to reduce disabling symptoms and improve
      quality-of-life of patients suffering from refractory angina. This review serves
      to update the clinician as to current evidence and future perspectives of the
      optimal utilization of this innovative technology.

PMID- 29020416
TI  - Fructose metabolism, cardiometabolic risk, and the epidemic of coronary artery
      disease.
AB  - Despite strong indications that increased consumption of added sugars correlates
      with greater risks of developing cardiometabolic syndrome (CMS) and
      cardiovascular disease (CVD), independent of the caloric intake, the worldwide
      sugar consumption remains high. In considering the negative health impact of
      overconsumption of dietary sugars, increased attention is recently being given to
      the role of the fructose component of high-sugar foods in driving CMS. The
      primary organs capable of metabolizing fructose include liver, small intestine,
      and kidneys. In these organs, fructose metabolism is initiated by ketohexokinase
      (KHK) isoform C of the central fructose-metabolizing enzyme KHK. Emerging data
      suggest that this tissue restriction of fructose metabolism can be rescinded in
      oxygen-deprived environments. In this review, we highlight recent progress in
      understanding how fructose metabolism contributes to the development of major
      systemic pathologies that cooperatively promote CMS and CVD, reference recent
      insights into microenvironmental control of fructose metabolism under stress
      conditions and discuss how this understanding is shaping preventive actions and
      therapeutic approaches.

PMID- 29020420
TI  - Treatment Burden in Neovascular AMD:Visual Acuity Outcomes are Associated With
      Anti-VEGF Injection Frequency.

PMID- 29020421
TI  - Optical Coherence Tomography Angiography Findings in Punctate Inner
      Choroidopathy.
AB  - BACKGROUND AND OBJECTIVE: Punctate inner choroidopathy (PIC) is an inflammatory
      chorioretinopathy characterized by multiple punctate, hypopigmented fundus
      lesions. Optical coherence tomography angiography (OCTA) is an emerging imaging
      modality that enables high-resolution visualization of the retinal and choroidal
      vasculature. The objective of this study is to examine the OCTA findings in PIC.
      PATIENTS AND METHODS: Observational, retrospective review of five patients with
      PIC. RESULTS: OCTA revealed several features in PIC lesions: distinctly visible
      choroidal neovascular membranes when present, as well as flow voids within the
      choroid and choriocapillaris layers that correspond with hypocyanescent lesions
      on indocyanine green angiography. CONCLUSION: OCTA may serve as a useful
      adjunctive imaging modality in diagnosing and monitoring patients with PIC.
      [Ophthalmic Surg Lasers Imaging Retina. 2017;48:786-792.].

PMID- 29020422
TI  - A Modified Foveal Advancement Technique in the Treatment of Persistent Large
      Macular Holes.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the outcomes of a new surgical technique on
      the closure of persistent large macular holes (MHs) PATIENTS AND METHODS:Data for
      10 eyes of 10 patients who underwent surgical intervention for the treatment of
      large and persistent MHs were reviewed retrospectively. After entrance of the
      three-port transconjunctival 23-gauge sutureless vitrectomy instruments, a
      shallow perihole retinal detachment was formed by injecting a small amount of
      fluid with a 39-gauge /41-gauge subretinal cannula under the perihole (superior,
      temporal, and inferior sparing nasal bundle fibers) retina. Edges of the hole
      were brought closer with small, passive aspirations by a silicone-tipped cannula.
      After fluid-air exchange, a 39-gauge /41-gauge cannula was placed over the hole
      to remove submacular fluid. Then air was changed with 20% sulfur hexafluoride
      endotamponade. RESULTS: Mean minimum hole diameter was 691 MUm +/- 98 MUm (range:
      500 MUm to 812 MUm), and mean basal diameter was 1,604 MUm +/- 321 MUm (range:
      1,066 MUm to 2,200 MUm). Preoperative best spectacle-corrected visual acuities
      (BSCVAs) were lower than 20/200 in eight patients and were 20/200 in two
      patients. MHs were successfully closed in all eyes (100%). BSCVA did not change
      in two patients and were lower than 20/200. BSCVAs were 20/200 in six patients
      and greater than 20/200 in two patients. The ellipsoid zone (EZ) was lost in all
      patients. CONCLUSIONS: All the large and persistent MHs were successfully closed
      and stayed closed during follow-up period. However, increase in visual acuities
      was limited, which was related to the loss of the EZ. The authors' modified
      technique seems to be a good option for the surgical treatment of large and
      persistent MHs. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:793-798.].

PMID- 29020414
TI  - Separate and combined associations of obesity and metabolic health with coronary
      heart disease: a pan-European case-cohort analysis.
AB  - Aims: The hypothesis of 'metabolically healthy obesity' implies that, in the
      absence of metabolic dysfunction, individuals with excess adiposity are not at
      greater cardiovascular risk. We tested this hypothesis in a large pan-European
      prospective study. Methods and results: We conducted a case-cohort analysis in
      the 520 000-person European Prospective Investigation into Cancer and Nutrition
      study ('EPIC-CVD'). During a median follow-up of 12.2 years, we recorded 7637
      incident coronary heart disease (CHD) cases. Using cut-offs recommended by
      guidelines, we defined obesity and overweight using body mass index (BMI), and
      metabolic dysfunction ('unhealthy') as >= 3 of elevated blood pressure,
      hypertriglyceridaemia, low HDL-cholesterol, hyperglycaemia, and elevated waist
      circumference. We calculated hazard ratios (HRs) and 95% confidence intervals
      (95% CI) within each country using Prentice-weighted Cox proportional hazard
      regressions, accounting for age, sex, centre, education, smoking, diet, and
      physical activity. Compared with metabolically healthy normal weight people
      (reference), HRs were 2.15 (95% CI: 1.79; 2.57) for unhealthy normal weight, 2.33
      (1.97; 2.76) for unhealthy overweight, and 2.54 (2.21; 2.92) for unhealthy obese
      people. Compared with the reference group, HRs were 1.26 (1.14; 1.40) and 1.28
      (1.03; 1.58) for metabolically healthy overweight and obese people, respectively.
      These results were robust to various sensitivity analyses. Conclusion:
      Irrespective of BMI, metabolically unhealthy individuals had higher CHD risk than
      their healthy counterparts. Conversely, irrespective of metabolic health,
      overweight and obese people had higher CHD risk than lean people. These findings
      challenge the concept of 'metabolically healthy obesity', encouraging population
      wide strategies to tackle obesity.

PMID- 29020419
TI  - Cortical GABA in Subjects at Ultra-High Risk of Psychosis: Relationship to
      Negative Prodromal Symptoms.
AB  - Background: Whilst robust preclinical and postmortem evidence suggests that
      altered GABAergic function is central to the development of psychosis, little is
      known about whether it is altered in subjects at ultra-high risk of psychosis, or
      its relationship to prodromal symptoms. Methods: Twenty-one antipsychotic naive
      ultra-high risk individuals and 20 healthy volunteers underwent proton magnetic
      resonance imaging at 3T. Gamma-aminobutyric acid levels were obtained from the
      medial prefrontal cortex using MEGA-PRESS and expressed as peak-area ratios
      relative to the synchronously acquired creatine signal. Gamma-aminobutyric acid
      levels were then related to severity of positive and negative symptoms as
      measured with the Community Assessment of At-Risk Mental States. Results: Whilst
      we found no significant difference in gamma-aminobutyric acid levels between
      ultra-high risk subjects and healthy controls (P=.130), in ultra-high risk
      individuals, medial prefrontal cortex GABA levels were negatively correlated with
      the severity of negative symptoms (P=.013). Conclusion: These findings suggest
      that gamma-aminobutyric acidergic neurotransmission may be involved in the
      neurobiology of negative symptoms in the ultra-high risk state.

PMID- 29020418
TI  - Striatal N-Acetylaspartate Synthetase Shati/Nat8l Regulates Depression-Like
      Behaviors via mGluR3-Mediated Serotonergic Suppression in Mice.
AB  - Background: Several clinical studies have suggested that N-acetylaspartate and N
      acetylaspartylglutamate levels in the human brain are associated with various
      psychiatric disorders, including major depressive disorder. We have previously
      identified Shati/Nat8l, an N-acetyltransferase, in the brain using an animal
      model of psychosis. Shati/Nat8l synthesizes N-acetylaspartate from L-aspartate
      and acetyl-coenzyme A. Further, N-acetylaspartate is converted into N
      acetylaspartylglutamate, a neurotransmitter for metabotropic glutamate receptor
      3. Methods: Because Shati/Nat8l mRNA levels were increased in the dorsal striatum
      of mice following the exposure to forced swimming stress, Shati/Nat8l was
      overexpressed in mice by the microinjection of adeno-associated virus vectors
      containing Shati/Nat8l gene into the dorsal striatum (dS-Shati/Nat8l mice). The
      dS-Shati/Nat8l mice were further assessed using behavioral and neurochemical
      tests. Results: The dS-Shati/Nat8l mice exhibited behavioral despair in the
      forced swimming and tail suspension tests and social withdrawal in the 3-chamber
      social interaction test. These depression-like behaviors were attenuated by the
      administration of a metabotropic glutamate receptor 2/3 antagonist and a
      selective serotonin reuptake inhibitor. Furthermore, the metabolism of N
      acetylaspartate to N-acetylaspartylglutamate was decreased in the dorsal striatum
      of the dS-Shati/Nat8l mice. This finding corresponded with the increased
      expression of glutamate carboxypeptidase II, an enzyme that metabolizes N
      acetylaspartylglutamate present in the extracellular space. Extracellular
      serotonin levels were lower in the dorsal striatum of the dS-Shati/Nat8l and
      normal mice that were repeatedly administered a selective glutamate
      carboxypeptidase II inhibitor. Conclusions: Our findings indicate that the
      striatal expression of N-acetylaspartate synthetase Shati/Nat8l plays a role in
      major depressive disorder via the metabotropic glutamate receptor 3-mediated
      functional control of the serotonergic neuronal system.

PMID- 29020423
TI  - Noninvasive, High-Resolution Functional Macular Imaging in Subjects With Retinal
      Vein Occlusion.
AB  - BACKGROUND AND OBJECTIVES: Several imaging modalities have been developed to
      characterize ischemia inherent in retinal vascular diseases. This study aims to
      predict the impact and to better establish the mechanisms of visual
      deterioration. A high-resolution functional imaging device is used, yielding
      quantitative data for macular blood flow and capillary network features in
      healthy eyes and in eyes with central retinal vein occlusion (CRVO) or branch
      retinal vein occlusion (BRVO). PATIENTS AND METHODS: This prospective, cross
      sectional, comparative case series measured blood flow velocities (BFVs) and
      noninvasive capillary perfusion maps (nCPMs) in macular vessels in patients with
      BRVO/CRVO and in healthy controls using the Retinal Function Imager (RFI; Optical
      Imaging, Rehovot, Israel). RESULTS: Twenty-two eyes of 21 subjects were studied
      (eight with CRVO, five with BRVO, and nine controls). A significant decrease was
      observed in the BFVs of both arterioles and venules in the affected macular
      region of patients with CRVO and BRVO (2.84 +/- 1.21 mm/s and 2.67 +/- 1.43 mm/s
      in CRVO/BRVO arterioles, respectively, vs. 4.23 +/- 1.04 mm/s in healthy
      controls, P < .001; and 1.64 +/- 0.51 mm/s and 1.60 +/- 0.41 mm/s in CRVO/BRVO
      venules, respectively, vs. 2.88 +/- 0.93 mm/s in healthy controls, P < .001).
      BFVs in non-affected macular regions of patients with BRVO were not statistically
      different from BFVs in healthy eyes (3.84 +/- 1.04 mm/s and 3.17 +/- 1.39 mm/s in
      BRVO patients vs. 4.23 +/- 1.04 mm/s and 2.88 +/- 0.93 mm/s in healthy controls'
      arterioles and venules, respectively; P >= .1). nCPMs allowed high-resolution
      imaging of the macular vasculature and successfully demonstrated ischemic areas
      in the RVO groups. CONCLUSIONS: The RFI provided high-resolution functional
      imaging of the retinal microvasculature and enabled quantitative measurement of
      BFVs in patients with RVO. Diminished flow velocity in arterioles and venules
      raises the possibility that RVO represents a panvascular compromise not confined
      to just venous stasis or its secondary arteriolar effects. The RFI offers
      potential to help with diagnosis and management of RVO cases. [Ophthalmic Surg
      Lasers Imaging Retina. 2017;48:799-809.].

PMID- 29020424
TI  - Characterization of Artifacts Associated With Multicolor Confocal Scanning Laser
      Ophthalmoscopy.
AB  - BACKGROUND AND OBJECTIVE: To characterize the appearance of three types of
      artifacts observed on multicolor confocal scanning laser ophthalmoscopy (cSLO).
      PATIENTS AND METHODS: Retrospective review of 159 eyes of 96 consecutive patients
      from the Duke Eye Center who underwent multicolor cSLO with spectral-domain
      optical coherence tomography (SD-OCT). Infrared (IR), green, blue, and multicolor
      reflectance images were evaluated for artifacts with corresponding SD-OCT scans
      available for reference. RESULTS: Multicolor cSLO artifacts were detected in
      23.3% (37 of 159) of eyes and comprised three main patterns: spot, wisp, and net.
      Only three instances of these artifacts were detected on IR reflectance versus
      34, 37, and 35 instances on green, blue, and multicolor reflectance,
      respectively. Artifacts were observed in 0% of eyes with clear lenses, 27.7% of
      eyes with cataracts, and in 20.8% of eyes with posterior chamber intraocular
      lenses. CONCLUSION: Awareness of spot, wisp, and net artifacts when interpreting
      multicolor cSLO images may facilitate the identification of true retinal
      pathology. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:810-815.].

PMID- 29020425
TI  - Changes in Subfoveal Choroidal Thickness During Pregnancy and After Delivery.
AB  - BACKGROUND AND OBJECTIVE: This study was performed to investigate longitudinal
      changes in the subfoveal choroidal thickness (SFCT) during pregnancy and after
      delivery. PATIENTS AND METHODS: The SFCT was measured in the first and third
      trimesters, shortly after delivery, and 1 month after delivery in 25 eyes of 25
      women. Enhanced depth imaging optical coherence tomography was used for
      measurement. RESULTS: The mean SFCT was 347 MUm +/- 86 MUm, 329 MUm +/- 81 MUm,
      333 MUm +/- 81 MUm, and 330 MUm +/- 87 MUm in the first and third trimesters,
      shortly after delivery, and 1 month after delivery, respectively. The SFCT in the
      first trimester was significantly greater than that in the third trimester,
      shortly after delivery, and 1 month after delivery. CONCLUSIONS: This study
      indicates that the SFCT is greater in the first trimester and decreases in the
      third trimester of pregnancy. The SFCT does not subsequently change until 1 month
      after delivery. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:816-821.].

PMID- 29020426
TI  - Aflibercept in Serous Foveal Detachment in Dome-Shaped Macula: Short-Term Results
      in a Retrospective Study.
AB  - BACKGROUND AND OBJECTIVE: To evaluate short-term efficacy of intravitreal
      aflibercept (Eylea; Regeneron, Tarrytown, NY) in serous foveal detachment (SFD)
      in dome-shaped macula (DSM). PATIENTS AND METHODS: A retrospective,
      noncomparative case series. Three monthly aflibercept injections were
      administered. Early Treatment Diabetic Retinopathy Study best-corrected visual
      acuity (BCVA), optical coherence tomography central subfield thickness (CST), and
      subretinal fluid (SRF) at baseline and at 2 months and 4 months after the last
      injection were considered for statistical analysis. RESULTS: The authors reviewed
      nine eyes affected by SFD in DSM. Mean BCVA improved from 0.42 LogMAR at baseline
      to 0.33 LogMAR at final follow-up (P = .06), and mean CST and SRF reduced from
      347 MUm to 295 MUm (P = .09) and from 146 MUm to 99 MUm (P < .01), respectively.
      None of the considered eyes had resolution of the SRF. CONCLUSIONS: Three monthly
      aflibercept injections may improve BCVA and reduce CST and SRF in SFD of DSM.
      Further prospective studies are necessary to state the real efficacy of this
      approach. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:822-828.].

PMID- 29020427
TI  - Cabbage Leaf Inverted Flap ILM Peeling for Macular Hole: A Novel Technique.
AB  - Large macular holes have poor surgical outcomes with conventional vitrectomy and
      internal limiting membrane (ILM) peeling surgery, but improved anatomical closure
      rates have been seen with an inverted ILM flap technique. Many studies have been
      reported with modifications in the original inverted ILM technique that help in
      better retention of the flap over the macular hole. The authors describe a new
      technique of inverted ILM flap in a case of chronic, large, full-thickness
      macular holes, in which multiple ILM flaps were inverted over each other and the
      hole-like cabbage leaves. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:830
      832.].

PMID- 29020428
TI  - Improvement of Recalcitrant Diabetic Macular Edema After Peritoneal Dialysis.
AB  - Nephropathy may be an independent and contributory risk factor for diabetic
      macular edema (DME). A 69-year-old man who had previously been treated with
      panretinal laser photocoagulation for proliferative diabetic retinopathy as well
      as with steroid and anti-vascular endothelial growth factor injections for DME
      declined additional treatment for the DME, which was worse in the right eye. The
      DME was observed without further treatment for the next 36 months. Despite well
      controlled blood sugar, blood pressure, and lipid levels, the DME remained
      unchanged. Peritoneal dialysis was started due to end-stage renal disease. Three
      months after commencing dialysis, the DME improved significantly. [Ophthalmic
      Surg Lasers Imaging Retina. 2017;48:834-837.].

PMID- 29020429
TI  - Pachychoroid Pigment Epitheliopathy Associated With Tamoxifen.
AB  - Pachychoroid pigment epitheliopathy (PPE) is considered to be a forme fruste of
      central serous chorioretinopathy. Tamoxifen (Soltamax; Midatech Pharma, Raleigh,
      NC) has an anti-estrogenic effect on cytoplasmic estrogen receptors. Serum total
      testosterone, cortisol, and cortisone levels increase during tamoxifen therapy.
      Tamoxifen may cause hormone disturbance leading to the development of disorders
      in the pachychoroid spectrum. The authors present two cases of PPE associated
      with tamoxifen therapy. A 65-year-old woman (Patient 1) and a 52-year-old woman
      (Patient 2) had a recent history of tamoxifen therapy. PPE lesions were seen in
      both eyes of Patient 1 and in the right eye of Patient 2. [Ophthalmic Surg Lasers
      Imaging Retina. 2017;48:838-842.].

PMID- 29020430
TI  - Acute Exudative Polymorphous Paraneoplastic Vitelliform Maculopathy Managed With
      Intravitreal Aflibercept.
AB  - The authors report on two patients with bilateral acute exudative polymorphous
      paraneoplastic vitelliform maculopathy (AEPPVM) treated with intravitreal
      aflibercept (Eylea; Regeneron, Tarrytown, NY [marketed locally in Turkey by
      Bayer]). Underlying malignancy had been treated in each case, including breast
      carcinoma in one case and colon carcinoma in the other case. A macular
      vitelliform lesion was noted in the right eye and atrophic retinal pigment
      epithelial (RPE) changes were noted in the left eye of each case. Enhanced depth
      imaging optical coherence tomography (EDI-OCT) of the vitelliform lesion showed
      sensorineural retinal detachment, highly reflective subretinal material,
      ellipsoid loss in the right eye, and photoreceptor loss in both eyes of each
      patient. In both cases, the right eye with a vitelliform macular lesion was
      treated with intravitreal aflibercept (2.0 mg/0.05 mL) at monthly intervals for
      the first three injections and at bimonthly intervals for the following
      injections. Case 1 received a total of six injections and visual acuity (VA)
      increased from 20/70 to 20/50 at 10 months' follow-up. EDI-OCT showed slight
      gradual resolution of subretinal vitelliform material. Case 2 received three
      injections and VA increased from 20/100 to 20/40 at 4 months' follow-up with a
      decrease in the subretinal vitelliform deposit and intraretinal edema on EDI-OCT.
      Intravitreal aflibercept may control progression of APPVME in newly diagnosed
      cases by decreasing vascular leakage and stabilizing RPE function. [Ophthalmic
      Surg Lasers Imaging Retina. 2017;48:844-850.].

PMID- 29020431
TI  - Overloaded Dysfunctional RPE Leads to Delayed Absorption of Subretinal Fluid
      After Retinal Detachment Repair.
AB  - Persistent subretinal fluid (SRF) can impair visual recovery after vitrectomy or
      scleral buckling surgery for rhegmatogenous retinal detachment. Several
      hypotheses have been proposed for delayed absorption of SRF, but the etiology has
      not been clearly identified. The authors present a patient with persistent SRF
      after vitrectomy for retinal detachment who developed central serous
      chorioretinopathy (CSCR) during the postoperative period in the nonoperative eye.
      Thus, subclinical retinal pigment epithelial (RPE) dysfunction was likely present
      in the operative eye, and when overloaded with SRF after retinal detachment
      repair, this manifested as delayed absorption. This may be the first evidence for
      overloaded, dysfunctional RPE as the etiology for persistent SRF following
      otherwise uncomplicated retinal detachment repair. The authors propose that RPE
      dysfunction can manifest as CSCR or, when overloaded with SRF after RD repair, it
      can also manifest as delayed absorption of SRF. [Ophthalmic Surg Lasers Imaging
      Retina. 2017;48:852-855.].

PMID- 29020432
TI  - Acquired Nonpigmented Vitreous Cyst Associated With Lattice Degeneration.
AB  - A 63-year-old male presented with a round-shaped floater and visual obscuration
      in the right eye. Clinical evaluation showed a nonpigmented vitreous cyst
      connected to a lattice degeneration by a stalk. Immunostaining of the vitreous
      cyst obtained from vitrectomy showed its origin of retinal neuroepithelium. The
      cyst was formed by continuous vitreous traction, which might tear up the
      disrupted retina at the area of lattice degeneration. This report added the
      lattice degeneration to the list of causes for the acquired vitreous cyst.
      [Ophthalmic Surg Lasers Imaging Retina. 2017;48:856-858.].

PMID- 29020433
TI  - The Impact of Switching Anti-Vascular Endothelial Growth Factor Therapy in the
      Management of Exudative Age-Related Macular Degeneration.
AB  - Switching of anti-vascular endothelial growth factor (VEGF) therapy in the
      management of poorly responsive exudative age-related macular degeneration (AMD)
      has had suggested benefits in individual reports that have yet to be
      consolidated. In this retrospective review, 24 studies published between 2009 and
      2014 were identified. Reasons for switching included tachyphylaxis, health
      insurance coverage, cost issues, and nonresponse or inadequate response. Nine
      studies had data that could be used for comparison between studies. Median follow
      up was 10.6 months (range: 4.2 months to 21.8 months). Mean baseline visual
      acuity (VA) ranged from 0.42 logMar to 0.94 logMar (standard deviation [SD]
      range: 0.05 logMar to 0.50 logMar) and mean VA on final follow-up ranged from
      0.38 logMar to 0.78 logMar (SD range: 0.08 logMar to 0.50 logMar). Five of nine
      studies reported no statistically significant change in vision, and five of nine
      studies reported a statistically significant improvement in central retinal
      thickness. This review found that switching anti-VEGF did not confer significant
      improvement of VA, although it provided some anatomical improvement. Pertinent
      considerations for evaluating response following anti-VEGF therapy are also
      presented in this review. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:859
      869.].

PMID- 29020434
TI  - 8 Questions with Darius Moshfeghi.

PMID- 29020436
TI  - Short-course versus long-course intravenous therapy with the same antibiotic for
      severe community-acquired pneumonia in children aged two months to 59 months.
AB  - BACKGROUND: Pneumonia is a leading cause of childhood mortality from infectious
      disease, responsible for an estimated 1.3 million deaths annually in children
      under five years of age, many of which are in low-income countries. The World
      Health Organization recommends intravenous antibiotics for five days as first
      line treatment for children with severe pneumonia. Although controversy exists
      regarding the specific clinical features used to diagnose pneumonia, the criteria
      for diagnosis of severe pneumonia are better defined and are widely used to
      triage children for referral and second-line therapy.In 2011 it was estimated
      that approximately 120 million new cases of pneumonia occur globally each year in
      children under five years of age, of which 14 million become severe episodes.
      Hospitalisation for severe pneumonia in children places a significant burden on
      both patients and their families, including substantial expense, loss of routine,
      and decrease in quality of life. By reducing the duration of hospital treatment,
      healthcare burdens could potentially be reduced and treatment compliance may
      improve.This is an update of a review published in 2015. OBJECTIVES: To evaluate
      the efficacy of short-course (two to three days) versus long-course (five days)
      intravenous therapy (alone or in combination with oral antibiotics) with the same
      antibiotic for severe community-acquired pneumonia in children aged two months to
      59 months. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL; 2016, Issue 12), MEDLINE (1966 to December week 3,
      2016), Embase (1974 to 22 December 2016), and four trials registers (23 August
      2017), together with reference checking of all relevant trials and reviews.
      SELECTION CRITERIA: Randomised controlled trials evaluating the efficacy of short
      course (two to three days) versus long-course (five days) intravenous antibiotic
      therapy (alone or in combination with oral antibiotics) for severe pneumonia in
      children aged two months to 59 months. We excluded children with any other
      debilitating disease, including those infected with HIV. We also excluded
      children who had developed pneumonia during their hospital stay (i.e. with
      nosocomial infection). There was no restriction on the type of antibiotic used,
      the dose, or the frequency of dosing. DATA COLLECTION AND ANALYSIS: We used
      standard methodological procedures expected by Cochrane. MAIN RESULTS: Our
      searches identified 4295 records, however no studies met our predefined inclusion
      criteria. AUTHORS' CONCLUSIONS: We identified no randomised controlled trials
      comparing a short course (two to three days) of intravenous antibiotics compared
      to a long course (five days) for severe pneumonia in children aged two months to
      59 months that met our inclusion criteria.

PMID- 29020435
TI  - Blood pressure targets for the treatment of people with hypertension and
      cardiovascular disease.
AB  - BACKGROUND: Hypertension is a prominent preventable cause of premature morbidity
      and mortality. People with hypertension and established cardiovascular disease
      are at particularly high risk, so reducing blood pressure below standard targets
      may be beneficial. This strategy could reduce cardiovascular mortality and
      morbidity but could also increase adverse events. The optimal blood pressure
      target in people with hypertension and established cardiovascular disease remains
      unknown. OBJECTIVES: To determine if 'lower' blood pressure targets (<= 135/85
      mmHg) are associated with reduction in mortality and morbidity as compared with
      'standard' blood pressure targets (<= 140 to 160/ 90 to 100 mmHg) in the
      treatment of people with hypertension and a history of cardiovascular disease
      (myocardial infarction, angina, stroke, peripheral vascular occlusive disease).
      SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the
      following databases for randomized controlled trials up to February 2017: the
      Cochrane Hypertension Specialised Register, the Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World
      Health Organization International Clinical Trials Registry Platform, and
      ClinicalTrials.gov. We also searched the Latin American and Caribbean Health
      Science Literature Database (from 1982) and contacted authors of relevant papers
      regarding further published and unpublished work. There were no language
      restrictions. SELECTION CRITERIA: We included randomized controlled trials (RCTs)
      with more than 50 participants per group and at least six months follow-up. Trial
      reports needed to present data for at least one primary outcome (total mortality,
      serious adverse events, total cardiovascular events, cardiovascular mortality).
      Eligible interventions were lower target for systolic/diastolic blood pressure
      (<= 135/85 mmHg) compared with standard target for blood pressure (<= 140 to
      160/90 to 100 mmHg).Participants were adults with documented hypertension or who
      were receiving treatment for hypertension and cardiovascular history for
      myocardial infarction, stroke, chronic peripheral vascular occlusive disease or
      angina pectoris. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed search results and extracted data using standard methodological
      procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included six
      RCTs that involved a total of 9795 participants. Mean follow-up was 3.7 years
      (range 1.0 to 4.7 years). Five RCTs provided individual patient data for 6775
      participants.We found no change in total mortality (RR 1.05, 95% CI 0.90 to 1.22)
      or cardiovascular mortality (RR 0.96, 95% CI 0.77 to 1.21; moderate-quality
      evidence). Similarly, no differences were found in serious adverse events (RR
      1.02, 95% CI 0.95 to 1.11; low-quality evidence). There was a reduction in fatal
      and non fatal cardiovascular events (including myocardial infarction, stroke,
      sudden death, hospitalization or death from congestive heart failure) with the
      lower target (RR 0.87, 95% CI 0.78 to 0.98; ARR 1.6% over 3.7 years; low-quality
      evidence). There were more participant withdrawals due to adverse effects in the
      lower target arm (RR 8.16, 95% CI 2.06 to 32.28; very low-quality evidence).
      Blood pressures were lower in the lower' target group by 9.5/4.9 mmHg. More drugs
      were needed in the lower target group but blood pressure targets were achieved
      more frequently in the standard target group. AUTHORS' CONCLUSIONS: No evidence
      of a difference in total mortality and serious adverse events was found between
      treating to a lower or to a standard blood pressure target in people with
      hypertension and cardiovascular disease. This suggests no net health benefit from
      a lower systolic blood pressure target despite the small absolute reduction in
      total cardiovascular serious adverse events. There was very limited evidence on
      adverse events, which lead to high uncertainty. At present there is insufficient
      evidence to justify lower blood pressure targets (<= 135/85 mmHg) in people with
      hypertension and established cardiovascular disease. More trials are needed to
      answer this question.

PMID- 29020437
TI  - Does testosterone therapy raise the risk of VTE?

PMID- 29020439
TI  - Nonleachable Imidazolium-Incorporated Composite for Disruption of Bacterial
      Clustering, Exopolysaccharide-Matrix Assembly, and Enhanced Biofilm Removal.
AB  - Surface-grown bacteria and production of an extracellular polymeric matrix
      modulate the assembly of highly cohesive and firmly attached biofilms, making
      them difficult to remove from solid surfaces. Inhibition of cell growth and
      inactivation of matrix-producing bacteria can impair biofilm formation and
      facilitate removal. Here, we developed a novel nonleachable antibacterial
      composite with potent antibiofilm activity by directly incorporating
      polymerizable imidazolium-containing resin (antibacterial resin with carbonate
      linkage; ABR-C) into a methacrylate-based scaffold (ABR-modified composite; ABR
      MC) using an efficient yet simplified chemistry. Low-dose inclusion of
      imidazolium moiety (~2 wt %) resulted in bioactivity with minimal cytotoxicity
      without compromising mechanical integrity of the restorative material. The
      antibiofilm properties of ABR-MC were assessed using an exopolysaccharide-matrix
      producing (EPS-matrix-producing) oral pathogen (Streptococcus mutans) in an
      experimental biofilm model. Using high-resolution confocal fluorescence imaging
      and biophysical methods, we observed remarkable disruption of bacterial
      accumulation and defective 3D matrix structure on the surface of ABR-MC.
      Specifically, the antibacterial composite impaired the ability of S. mutans to
      form organized bacterial clusters on the surface, resulting in altered biofilm
      architecture with sparse cell accumulation and reduced amounts of EPS matrix
      (versus control composite). Biofilm topology analyses on the control composite
      revealed a highly organized and weblike EPS structure that tethers the bacterial
      clusters to each other and to the surface, forming a highly cohesive unit. In
      contrast, such a structured matrix was absent on the surface of ABR-MC with
      mostly sparse and amorphous EPS, indicating disruption in the biofilm physical
      stability. Consistent with lack of structural organization, the defective biofilm
      on the surface of ABR-MC was readily detached when subjected to low shear stress,
      while most of the biofilm biomass remained on the control surface. Altogether, we
      demonstrate a new nonleachable antibacterial composite with excellent antibiofilm
      activity without affecting its mechanical properties, which may serve as a
      platform for development of alternative antifouling biomaterials.

PMID- 29020440
TI  - Influence of DNA Lesions on Polymerase-Mediated DNA Replication at Single
      Molecule Resolution.
AB  - Faithful replication of DNA is a critical aspect in maintaining genome integrity.
      DNA polymerases are responsible for replicating DNA, and high-fidelity
      polymerases do this rapidly and at low error rates. Upon exposure to exogenous or
      endogenous substances, DNA can become damaged and this can alter the speed and
      fidelity of a DNA polymerase. In this instance, DNA polymerases are confronted
      with an obstacle that can result in genomic instability during replication, for
      example, by nucleotide misinsertion or replication fork collapse. It is important
      to know how DNA polymerases respond to damaged DNA substrates to understand the
      mechanism of mutagenesis and chemical carcinogenesis. Single-molecule techniques
      have helped to improve our current understanding of DNA polymerase-mediated DNA
      replication, as they enable the dissection of mechanistic details that can
      otherwise be lost in ensemble-averaged experiments. These techniques have also
      been used to gain a deeper understanding of how single DNA polymerases behave at
      the site of the damage in a DNA substrate. In this review, we evaluate single
      molecule studies that have examined the interaction between DNA polymerases and
      damaged sites on a DNA template.

PMID- 29020441
TI  - Three-Dimensional Printing of Nano Hydroxyapatite/Poly(ester urea) Composite
      Scaffolds with Enhanced Bioactivity.
AB  - Polymer-bioceramic composites incorporate the desirable properties of each
      material while mitigating the limiting characteristics of each component. 1,6
      Hexanediol l-phenylalanine-based poly(ester urea) (PEU) blended with
      hydroxyapatite (HA) nanocrystals were three-dimensional (3D) printed into porous
      scaffolds (75% porosity) via fused deposition modeling and seeded with MC3T3-E1
      preosteoblast cells in vitro to examine their bioactivity. The resulting 3D
      printed scaffolds exhibited a compressive modulus of ~50 MPa after a 1-week
      incubation in PBS at 37  degrees C, cell viability >95%, and a composition
      dependent enhancement of radio-contrast. The influence of HA on MC3T3-E1
      proliferation and differentiation was measured using quantitative real-time
      polymerase chain reaction, immunohistochemistry and biochemical assays. After 4
      weeks, alkaline phosphatase activity increased significantly for the 30% HA
      composite with values reaching 2.5-fold greater than the control. Bone
      sialoprotein showed approximately 880-fold higher expression and 15-fold higher
      expression of osteocalcin on the 30% HA composite compared to those of the
      control. Calcium quantification results demonstrated a 185-fold increase of
      calcium concentration in mineralized extracellular matrix deposition after 4
      weeks of cell culture in samples with higher HA content. 3D printed HA-containing
      PEU composites promote bone regeneration and have the potential to be used in
      orthopedic applications.

PMID- 29020442
TI  - Two-Photon Photosensitizer-Polymer Conjugates for Combined Cancer Cell Death
      Induction and Two-Photon Fluorescence Imaging: Structure/Photodynamic Therapy
      Efficiency Relationship.
AB  - One of the challenges of photodynamic therapy is to increase the penetration
      depth of light irradiation in the tumor tissues. Although two-photon excitation
      strategies have been developed, the two-photon absorption cross sections of
      clinically used photosensitizers are generally low (below 300 GM). Besides,
      photosensitizers with high cross section values are often non-water-soluble. In
      this research work, a whole family of photosensitizer-polymer conjugates was
      synthesized via the covalent binding of a photosensitizer with a relatively high
      cross section along a biocompatible copolymer chain. The resulting
      photosensitizer-polymer conjugates were water-soluble and could be imaged in
      cellulo by two-photon microscopy thanks to their high two-photon absorption cross
      sections (up to 2600 GM in water, in the NIR range). In order to explore the
      structure/photodynamic activity relationship of such macromolecular
      photosensitizers, the influence of the polymer size, photosensitizer density, and
      presence of charges along the polymer backbone was investigated (neutral,
      anionic, cationic, and zwitterionic conjugates were compared). The macromolecular
      photosensitizers were not cytotoxic in the absence of light irradiation. Their
      kinetics of cellular uptake in the B16-F10 melanoma cell line were followed by
      flow cytometry over 24 h. The efficiency of cell death upon photoactivation was
      found to be highly correlated to the cellular uptake in turn correlated to the
      global charge of the macromolecular photosensitizer which appeared as the
      determining structural parameter.

PMID- 29020443
TI  - Solution Conformation of Polymer Brushes Determines Their Interactions with DNA
      and Transfection Efficiency.
AB  - Polymer brush-functionalized nanomaterials offer interesting features for the
      design of gene delivery vectors as their physicochemical and structural
      properties can be designed independently of the chemistry, size and shape of the
      nanomaterial core. However, little is known of the parameters regulating the
      adsorption and infiltration of DNA molecules at the surface of positively charged
      polymer brushes, despite the importance of such processes for gene delivery. Here
      we investigate the role of the molecular environment (e.g., pH, type of buffer,
      concentration) on the interactions between plasmid DNA and positively charged
      poly(dimethylaminoethyl methacrylate) (PDMAEMA) brushes using a combination of
      light scattering, electrophoretic light scattering, in situ ellipsometry, and
      surface plasmon resonance. We show that the conformation of swollen PDMAEMA
      brushes is modulated by the surrounding buffer and that this impacts strongly on
      the ability of such brushes and nanomaterials based on these coatings to complex
      DNA molecules. In turn, the levels of transfection efficiency measured correlate
      with changes in brush conformation and DNA binding. Therefore, this work
      demonstrates the importance of molecular design of polymer brushes to control DNA
      complexation and release in order to optimize the performance of polymer brush
      functionalized nanomaterials for gene delivery applications.

PMID- 29020444
TI  - Biologically Complex Planar Cell Plasma Membranes Supported on Polyelectrolyte
      Cushions Enhance Transmembrane Protein Mobility and Retain Native Orientation.
AB  - Reconstituted supported lipid bilayers (SLB) are widely used as in vitro cell
      surface models because they are compatible with a variety of surface-based
      analytical techniques. However, one of the challenges of using SLBs as a model of
      the cell surface is the limited complexity in membrane composition, including the
      incorporation of transmembrane proteins and lipid diversity that may impact the
      activity of those proteins. Additionally, it is challenging to preserve the
      transmembrane protein native orientation, function, and mobility in SLBs. Here,
      we leverage the interaction between cell plasma membrane vesicles and
      polyelectrolyte brushes to create planar bilayers from cell plasma membrane
      vesicles that have budded from the cell surface. This approach promotes the
      direct incorporation of membrane proteins and other species into the planar
      bilayer without using detergent or reconstitution and preserves membrane
      constituents. Furthermore, the structure of the polyelectrolyte brush serves as a
      cushion between the planar bilayer and rigid supporting surface, limiting the
      interaction of the cytosolic domains of membrane proteins with this surface.
      Single particle tracking was used to analyze the motion of GPI-linked yellow
      fluorescent proteins (GPI-YFP) and neon-green fused transmembrane P2X2 receptors
      (P2X2-neon) and shows that this platform retains over 75% mobility of multipass
      transmembrane proteins in its native membrane environment. An enzyme
      accessibility assay confirmed that the protein orientation is preserved and
      results in the extracellular domain facing toward the bulk phase and the
      cytosolic side facing the support. Because the platform presented here retains
      the complexity of the cell plasma membrane and preserves protein orientation and
      mobility, it is a better representative mimic of native cell surfaces, which may
      find many applications in biological assays aimed at understanding cell membrane
      phenomena.

PMID- 29020445
TI  - Direct Metal Writing and Precise Positioning of Gold Nanoparticles within
      Microfluidic Channels for SERS Sensing of Gaseous Analytes.
AB  - We demonstrate a one-step precise direct metal writing of well-defined and
      densely packed gold nanoparticle (AuNP) patterns with tunable physical and
      optical properties. We achieve this by using two-photon lithography on a Au
      precursor comprising poly(vinylpyrrolidone) (PVP) and ethylene glycol (EG), where
      EG promotes higher reduction rates of Au(III) salt via polyol reduction. Hence,
      clusters of monodisperse AuNP are generated along raster scanning of the laser,
      forming high-particle-density, well-defined structures. By varying the PVP
      concentration, we tune the AuNP size from 27.3 to 65.0 nm and the density from
      172 to 965 particles/MUm2, corresponding to a surface roughness of 12.9 to 67.1
      nm, which is important for surface-based applications such as surface-enhanced
      Raman scattering (SERS). We find that the microstructures exhibit an SERS
      enhancement factor of >105 and demonstrate remote writing of well-defined Au
      microstructures within a microfluidic channel for the SERS detection of gaseous
      molecules. We showcase in situ SERS monitoring of gaseous 4-methylbenzenethiol
      and real-time detection of multiple small gaseous species with no specific
      affinity to Au. This one-step, laser-induced fabrication of AuNP microstructures
      ignites a plethora of possibilities to position desired patterns directly onto or
      within most surfaces for the future creation of multifunctional lab-on-a-chip
      devices.

PMID- 29020447
TI  - Efficiently Synergistic Hydrogen Evolution Realized by Trace Amount of Pt
      Decorated Defect-Rich SnS2 Nanosheets.
AB  - The electrocatalytic hydrogen evolution reaction (HER) has attracted increasing
      attention in the field of hydrogen-based economy, whereat developing cheap and
      efficient catalysts to reduce the use of Pt-based catalysts is highly required.
      Tin disulfide (SnS2) as a new rising star has exhibited intriguing properties in
      energy storage and conversion applications, while showing slow progress in HER
      due to the inherent poor activity. Herein, we demonstrate the successful
      structural engineering and simultaneous integration of trace amount Pt in SnS2
      nanosheets via a facile and effective in situ cycling voltammetry activation
      process, leading to the efficiently synergistic HER. Defect-rich SnS2 nanosheets
      decorated with a trace amount (0.37 wt %) of Pt exhibit greatly enhanced HER
      activity due to the synergy between them, revealing low onset potential of 32 mV
      and overpotential of 117 mV at 10 mA/cm2, small Tafel slope of 69 mV/dec, and
      large exchange current density of 394.46 MUA/cm2. Present work provides an
      intriguing strategy for developing ultralow loading Pt electrocatalysts with high
      HER performance.

PMID- 29020446
TI  - Desymmetrization of Diarylmethylamido Bis(phenols) through Peptide-Catalyzed
      Bromination: Enantiodivergence as a Consequence of a 2 amu Alteration at an
      Achiral Residue within the Catalyst.
AB  - Diarylmethylamido bis(phenols) have been subjected to peptide-catalyzed,
      enantioselective bromination reactions. Desymmetrization of compounds in this
      class has been achieved such that enantioenriched products may be isolated with
      up to 97:3 er. Mechanistically, the observed enantioselectivity was shown to be
      primarily a function of differential functionalization of enantiotopic arenes,
      although additional studies unveiled a contribution from secondary kinetic
      resolution of the product (to afford the symmetrical dibromide) under the
      reaction conditions. Variants of the tetrapeptide catalyst were also evaluated
      and revealed a striking observation-enantiodivergent catalysis is observed upon
      changing the achiral amino acid residue in the catalyst (at the i+2 position)
      from an aminocyclopropane carboxamide residue (97:3 er) to an aminoisobutyramide
      residue (33:67 er) under a common set of conditions. An expanded set of catalysts
      was also evaluated, enabling structure/selectivity correlations to be considered
      in a mechanistic light.

PMID- 29020449
TI  - Light-Induced Reactions of Diazotetrahydrofuranone without Elimination of
      Nitrogen: Experimental and Mechanistic Study.
AB  - The energies and lifetimes of the excited states (S1, S2, S5, T1) of a
      diazotetrahydrofuranone were determined using experimental and computational
      methods. It was shown that direction of the diazoketone photochemical
      transformations without elimination of nitrogen is determined by multiplicity and
      energy of the excited state, generated by UV irradiation of diazo compound:
      isomerization to alpha-ketodiazirine proceeds from the singlet S1 state, whereas
      the alternative process of C-H insertion with hydrazone formation occurs through
      the triplet T1 state. The most probable excited state that leads to elimination
      of nitrogen and Wolff rearrangement is one of the highest singlet excited states
      of diazotetrahydrofuranone.

PMID- 29020448
TI  - Preparation of Tc99m-Labeled Pseudomonas Bacteriophage without Adversely
      Impacting Infectivity or Biodistribution.
AB  - Bacteriophages (phages) are ubiquitous viruses which have adapted to infect and
      replicate within target bacteria, their only known hosts, in a strain specific
      fashion with minimal cross infectivity. The recent steep rise in antibiotic
      resistance throughout the world has renewed interest in adapting phages for the
      imaging and treatment of bacterial infection in humans. In this article, we
      describe the current limitations surrounding the radiolabeling of phage for the
      imaging and treatment of bacterial infection and methods to overcome these
      difficulties. Specifically, we examined the effects of hydrazinonicotinamide
      conjugation and removal of bacterial DNA on the infectivity, biodistribution, and
      radionuclide imaging of a phage lytic for a clinically relevant strain of
      Pseudomonas aeruginosa, a common Gram-negative bacterial pathogen often resistant
      to multiple antibiotics. We found that all but the briefest reaction of
      concentrated phage with hydrazinonicotinamide (<=3 min) resulted in nearly
      complete loss of infectivity. Furthermore, we determined that digestion and
      removal of bacterial DNA was needed to avoid high nonspecific uptake of
      hydrazinonicotinamide-labeled phage within the liver and spleen as well as
      prolonged circulation in the blood. We also demonstrate the surprisingly wide
      soft tissue and organ biodistribution and rapid pharmacokinetics of 99mTc
      hydrazinonicotinamide-labeled phage in normal mice as well as its imaging
      characteristics and efficacy in wounded mice infected with bioluminescent
      Pseudomonas aeruginosa. In conclusion, the preservation of phage infectivity and
      removal of all bacterial containments including DNA are critical methodologic
      considerations in the labeling of phages for imaging and therapy.

PMID- 29020451
TI  - Diastereoselective Desymmetrization of Prochiral Cyclopentenediones via
      Cycloaddition Reaction with N-Phenacylbenzothiazolium Bromides.
AB  - A metal-free highly diastereoselctive [3 + 2] cycloaddition reaction has been
      developed between N-phenacylbenzothiazolium bromides and prochiral cyclopentene
      1,3-diones. The active 1,3 dipole benzothiazolium N-phenacylide was generated in
      situ with the treatment of DIPEA, and the corresponding cycloaddition products
      were obtained in excellent yields under mild reaction conditions. The scope of
      the reaction is quite broad, tolerating a variety of aryl and heteroaromatic
      groups. A catalytic asymmetric approach was also studied preliminarily, and
      moderate enantioselectivity was achieved.

PMID- 29020450
TI  - Highly Effective Antibacterial Vesicles Based on Peptide-Mimetic Alternating
      Copolymers for Bone Repair.
AB  - It is an important challenge for bone repair to effectively deliver growth
      factors and at the same time to prevent and cure inflammation without obvious
      pathogen resistance. We designed a kind of antibacterial peptide-mimetic
      alternating copolymers (PMACs) to effectively inhibit and kill both Gram-positive
      and Gram-negative bacteria. The minimum inhibition concentrations (MICs) of the
      PMACs against E. coli and S. aureus are 8.0 MUg/mL, which are much lower than
      that of antibacterial peptides synthesized by other methods such as widely used
      ring-opening polymerization of N-carboxyanhydride. Furthermore, the PMACs can
      self-assemble into polymer vesicles (polymersomes) in pure water with low
      cytotoxicity (IC50 > 1000 MUg/mL), which can encapsulate growth factors in
      aqueous solution and release them during long-term antibacterial process for
      facilitating bone repair. We also find that the alternating structure is
      essential for the excellent antibacterial activity. The in vivo tests in rabbits
      confirmed that the growth-factor-encapsulated antibacterial vesicles have better
      bone repair ability compared with control groups without antibacterial vesicles.
      Overall, we have provided a novel method for designing PMAC-based highly
      effective intrinsically antibacterial vesicles that may have promising biomedical
      applications in the future.

PMID- 29020452
TI  - Heterogeneous Ice Nucleation: Interplay of Surface Properties and Their Impact on
      Water Orientations.
AB  - Ice is ubiquitous in nature, and heterogeneous ice nucleation is the most common
      pathway of ice formation. How surface properties affect the propensity to observe
      ice nucleation on that surface remains an open question. We present results of
      molecular dynamics studies of heterogeneous ice nucleation on model surfaces. The
      models surfaces considered emulate the chemistry of kaolinite, an abundant
      component of mineral dust. We investigate the interplay of surface lattice and
      hydrogen bonding properties in affecting ice nucleation. We find that lattice
      matching and hydrogen bonding are necessary but not sufficient conditions for
      observing ice nucleation at these surfaces. We correlate this behavior to the
      orientations sampled by the metastable supercooled water in contact with the
      surfaces. We find that ice is observed in cases where water molecules not only
      sample orientations favorable for bilayer formation but also do not sample
      unfavorable orientations. This distribution depends on both surface-water and
      water-water interactions and can change with subtle modifications to the surface
      properties. Our results provide insights into the diverse behavior of ice
      nucleation observed at different surfaces and highlight the complexity in
      elucidating heterogeneous ice nucleation.

PMID- 29020456
TI  - The management of neuroendocrine tumours: A nutritional viewpoint.
AB  - Nutritional status in patients with neuroendocrine tumours (NETs), especially of
      gastroenteropancreatic origin, can be deeply affected by excessive production of
      gastrointestinal hormones, peptides, and amines, which can lead to malabsorption,
      diarrhoea, steatorrhea, and altered gastrointestinal motility. Besides, the
      surgical and/or medical management of NETs can lead to alteration of
      gastrointestinal secretory, motor, and absorptive functions, with both dietary
      and nutritional consequences. Indeed, disease-related malnutrition is a
      frequently encountered yet both underrecognized and understudied clinical
      phenomenon in patients with NETs, with substantial prognostic and socioeconomic
      consequences. Most of these conditions can be alleviated by a tailored
      nutritional approach, also with the aim of improving the efficacy of cancer
      treatments. In this setting, skilled nutritionists can play a fundamental role in
      the multidisciplinary health care team in NETs management and their presence
      should be recommended. The aim of this review is to provide dietary advices for
      each specific condition in patients with NETs, underlining the importance of a
      nutritional approach to treat malnutrition in this setting. Further, we will
      provide preliminary evidence coming from our data on the assessment of
      nutritional status in a single cohort of patients with NETs.

PMID- 29020455
TI  - The U.S. Food and Drug Administration's Experience with Ivacaftor in Cystic
      Fibrosis. Establishing Efficacy Using In Vitro Data in Lieu of a Clinical Trial.
AB  - On May 17, 2017, the U.S. Food and Drug Administration expanded the patient
      population for use of ivacaftor to include patients with cystic fibrosis with
      relatively rare mutations in the cystic fibrosis transmembrane conductance
      regulator gene. The label expansion is unique in that clinical efficacy was not
      based on clinical data but on in vitro assay data demonstrating increased
      chloride ion transport across cells in response to ivacaftor. Such an approach
      provides a pathway for adding difficult-to-study mutation-based cystic fibrosis
      subpopulations to the indication as well as defining mutations unresponsive to
      ivacaftor and has important implications for cystic fibrosis drug development and
      other rare genetic diseases whose genetics and disease pathophysiology are well
      understood.

PMID- 29020454
TI  - The absence of brain-specific link protein Bral2 in perineuronal nets hampers
      auditory temporal resolution and neural adaptation in mice.
AB  - Brain-specific link protein Bral2 represents a substantial component of
      perineuronal nets (PNNs) enwrapping neurons in the central nervous system. To
      elucidate the role of Bral2 in auditory signal processing, the hearing function
      in knockout Bral2(-/-) (KO) mice was investigated using behavioral and
      electrophysiological methods and compared with wild type Bral2(+/+) (WT) mice.
      The amplitudes of the acoustic startle reflex (ASR) and the efficiency of the
      prepulse inhibition of ASR (PPI of ASR), produced by prepulse noise stimulus or
      gap in continuous noise, was similar in 2-week-old WT and KO mice. Over the 2
      month postnatal period the increase of ASR amplitudes was significantly more
      evident in WT mice than in KO mice. The efficiency of the PPI of ASR
      significantly increased in the 2-month postnatal period in WT mice, whereas in KO
      mice the PPI efficiency did not change. Hearing thresholds in 2-month-old WT
      mice, based on the auditory brainstem response (ABR) recordings, were
      significantly lower at high frequencies than in KO mice. However, amplitudes and
      peak latencies of individual waves of click-evoked ABR did not differ
      significantly between WT and KO mice. Temporal resolution and neural adaptation
      were significantly better in 2-month-old WT mice than in age-matched KO mice.
      These results support a hypothesis that the absence of perineuronal net formation
      at the end of the developmental period in the KO mice results in higher hearing
      threshold at high frequencies and weaker temporal resolution ability in adult KO
      animals compared to WT mice.

PMID- 29020457
TI  - The Public Health Conundrum of Coal Mining.

PMID- 29020453
TI  - Small Angle Neutron Scattering Studies of R67 Dihydrofolate Reductase, a
      Tetrameric Protein with Intrinsically Disordered N-Termini.
AB  - R67 dihydrofolate reductase (DHFR) is a homotetramer with a single active site
      pore and no sequence or structural homology with chromosomal DHFRs. The R67
      enzyme provides resistance to trimethoprim, an active site-directed inhibitor of
      Escherichia coli DHFR. Sixteen to twenty N-terminal amino acids are intrinsically
      disordered in the R67 dimer crystal structure. Chymotrypsin cleavage of 16 N
      terminal residues results in an active enzyme with a decreased stability. The
      space sampled by the disordered N-termini of R67 DHFR was investigated using
      small angle neutron scattering. From a combined analysis using molecular dynamics
      and the program SASSIE ( http://www.smallangles.net/sassie/SASSIE_HOME.html ),
      the apoenzyme displays a radius of gyration (Rg) of 21.46 +/- 0.50 A. Addition of
      glycine betaine, an osmolyte, does not result in folding of the termini as the Rg
      increases slightly to 22.78 +/- 0.87 A. SASSIE fits of the latter SANS data
      indicate that the disordered N-termini sample larger regions of space and remain
      disordered, suggesting they might function as entropic bristles. Pressure
      perturbation calorimetry also indicated that the volume of R67 DHFR increases
      upon addition of 10% betaine and decreased at 20% betaine because of the
      dehydration of the protein. Studies of the hydration of full-length R67 DHFR in
      the presence of the osmolytes betaine and dimethyl sulfoxide find around 1250
      water molecules hydrating the protein. Similar studies with truncated R67 DHFR
      yield around 400 water molecules hydrating the protein in the presence of
      betaine. The difference of ~900 waters indicates the N-termini are well-hydrated.

PMID- 29020458
TI  - Phytoremediation of lead by a wild, non-edible Pb accumulator Coronopus didymus
      (L.) Brassicaceae.
AB  - Coronopus didymus was examined in terms of its ability to remediate Pb
      contaminated soils. Pot experiments were conducted for 4 and 6 weeks to compare
      the growth, biomass, photosynthetic efficiency, lead (Pb) uptake, and
      accumulation by C. didymus plants. The plants grew well having no visible toxic
      symptoms and 100% survivability, exposed to different Pb-spiked soils 100, 350,
      1500, and 2500 mg kg-1, supplied as lead nitrate. After 4 weeks, root and shoot
      concentrations reached 1652 and 502 mg Pb kg-1 DW, while after 6 weeks they
      increased up to 3091 and 527 mg Pb kg-1 DW, respectively, at highest Pb
      concentration. As compared to the 4 week experiments, the plant growth and
      biomass yield were higher after 6 weeks of Pb exposure. However, the chlorophyll
      content of leaves decreased but only a slight decline in photosynthetic
      efficiency was observed on exposure to Pb at both 4 and 6 weeks. The Pb
      accumulation was higher in roots than in the shoots. The bioconcentration factor
      of Pb was > 1 in all the plant samples, but the translocation factor was < 1.
      This suggested C. didymus as a good candidate for phytoremediation of Pb
      contaminated soils and can be used for future remediation purposes.

PMID- 29020459
TI  - Effect of pre-harvest and post-harvest conditions on the fruit allergenicity: A
      review.
AB  - Fruits are an important source of vitamins and antioxidants that can effectively
      delay aging and contribute to health and well-being of the human kind. However,
      they are growing to be one of the primary elicitors of food allergies around the
      world. Fruit allergens can induce an IgE-mediated (Immunoglobulin E) reaction,
      presenting with a symptom like localized oral allergy syndrome (OAS). Numerous
      studies showed that varying environmental and cultivation conditions can
      influence the fruit allergen content during flowering and ripening stages.
      Further, the variety, harvesting maturity, and storage conditions can also
      significantly influence the allergenicity potential. For example, unripe apples
      and tomatoes have lower levels of allergens compared to ripened fruits.
      Researchers have also reported that modified atmosphere packaging (MAP) can help
      reduce Mal d 3 content present in apples during storage. Post-harvest processing
      like peeling is also considered a good method to help reduce the overall
      allergenicity in few fruits whose peel might contain majority of the allergens.
      This review will discuss the overall influence of both pre-harvest and post
      harvest factors on the fruit allergens. We will also discuss the progress
      regarding the cause, symptoms and diagnostic methods of fruit based allergies.

PMID- 29020460
TI  - Toxoplasma gondii infection and food consumption: A systematic review and meta
      analysis of case-controlled studies.
AB  - BACKGROUND: Toxoplasmosis is a zoonotic disease causing severe symptoms in
      pregnant women and immunocompromised individuals. On average, worldwide, around
      30% of people are seropositive. The oral transmission route is of great
      significance and food, particularly meat, is an important transmission vehicle
      for T. gondii. However, the role of different food matrices is debated.
      OBJECTIVES: The aim of this review was to assess the risk of humans developing
      acute T. gondii infection via the foodborne route. STUDY ELIGIBILITY CRITERIA:
      Case-control studies including acute cases of T. gondii infection were included
      after literature searches, without time limits, in several databases. All studies
      estimating the risk of acquiring T. gondii infection after consumption of
      specific food categories were included. RESULTS: Three risk factors proved to be
      significantly associated with acute T. gondii infection in humans: consumption of
      raw/undercooked meat, Odds Ratio (OR) 3.44 (1.29-9.16), consumption of
      raw/undercooked beef, OR 2.22 (1.57-3.12), and consumption of raw/undercooked
      sheep meat, OR 3.85 (1.85-8.00). Consumption of raw/undercooked pork, raw eggs,
      and unpasteurized milk proved to be non-significant risk factors. LIMITATIONS:
      Limitations in the present review and meta-analysis are due to the low number of
      case-control studies available for analysis and the lack of a search strategy
      targeting gray literature. CONCLUSION: Consumption of raw/undercooked beef and
      sheep meat are important risk factors for T. gondii infection. Their consumption
      should be avoided in order to prevent toxoplasmosis, particularly by those in at
      risk categories, including pregnant women. The review protocol is registered in
      PROSPERO database (CRD42016043295).

PMID- 29020461
TI  - Peptides: Production, bioactivity, functionality, and applications.
AB  - Production of peptides with various effects from proteins of different sources
      continues to receive academic attention. Researchers of different disciplines are
      putting increasing efforts to produce bioactive and functional peptides from
      different sources such as plants, animals, and food industry by-products. The aim
      of this review is to introduce production methods of hydrolysates and peptides
      and provide a comprehensive overview of their bioactivity in terms of their
      effects on immune, cardiovascular, nervous, and gastrointestinal systems.
      Moreover, functional and antioxidant properties of hydrolysates and isolated
      peptides are reviewed. Finally, industrial and commercial applications of
      bioactive peptides including their use in nutrition and production of
      pharmaceuticals and nutraceuticals are discussed.

PMID- 29020462
TI  - Syk inhibitor R406 downregulates inflammation in an in vitro model of Pseudomonas
      aeruginosa infection.
AB  - As Pseudomonas aeruginosa infections are characterized by strong inflammation of
      infected tissues, anti-inflammatory therapies in combination with antibiotics
      have been considered for the treatment of associated diseases. Syk tyrosine
      kinase is an important regulator of inflammatory responses, and its specific
      inhibition was explored as a therapeutic option in several inflammatory
      conditions; however, this has not been studied in bacterial infections. We used a
      model of in vitro infection of human monocytic cell line THP-1 and lung
      epithelial cell line H292 with both wild-type and flagella-deficient mutant of P.
      aeruginosa strain K, as well as with clinical isolates from cystic fibrosis
      patients, to study the effect of a small molecule Syk inhibitor R406 on
      inflammatory responses induced by this pathogen. One-hour pretreatment of THP-1
      cells with 10 MUmol/L R406 resulted in a significant downregulation of the
      expression of the adhesion molecule ICAM-1, pro-inflammatory cytokines TNF-alpha
      and IL-1beta, and phosphorylated signaling proteins ERK2, JNK, p-38, and
      IkappaBalpha, as well as significantly decreased TNF-alpha release by infected
      H292 cells. The results suggest that Syk is involved in the regulation of
      inflammatory responses to P. aeruginosa, and R406 may potentially be useful in
      dampening the damage caused by severe inflammation associated with this
      infection.

PMID- 29020464
TI  - Invited Commentary. The Royalty of Evidence: The Randomized Control Trials.

PMID- 29020463
TI  - The role of human rhinovirus (HRV) species on asthma exacerbation severity in
      children and adolescents.
AB  - OBJECTIVE: It is recognized that human rhinovirus (HRV) infection is an important
      factor in asthma exacerbations requiring hospitalization in children. However,
      previous studies have disagreed on the differential impact of various HRV
      species. We sought to assess the impact of HRV species on the severity of asthma
      exacerbations in children and adolescents. We also examined whether the effect of
      HRV species on severity was modified by age and gender. METHODS: Virus strain was
      determined for 113 children with HRV detectable at the time of admission for
      asthma exacerbation. Patient characteristics were collected on admission and
      exacerbation severity was scored using several validated scales. RESULTS: HRV
      species by itself was not associated with moderate/severe vs. mild exacerbations.
      Boys with HRV-C infections were more likely (OR: 3.7, 95% CI: 1.2-13.4) to have a
      moderate/severe exacerbation than girls with HRV-C (p = 0.04 for interaction
      term). Higher odds were observed in younger boys (3 years old: OR: 9.1, 95% CI:
      1.8-47.1 vs 5 years old: OR: 3.3, 95% CI: 0.9-11.8 vs 7 years old: OR: 1.2, 95%
      CI: 0.2-6.6). In contrast, children with HRV-C infection and sensitized to pollen
      during the pollen season were less likely to have moderate/severe exacerbations
      (p = 0.01 for the interaction term). CONCLUSION: Acute asthma exacerbations are
      more likely to be moderate/severe in boys under 5 years of age who had HRV-C
      infection on admission. The opposite was found in children with sensitization to
      pollen during pollen season.

PMID- 29020465
TI  - Donor sperm insemination after failed intra-couple intracytoplasmic sperm
      injection.
AB  - : The purpose of the present multicenter study was to investigate whether an
      artificial insemination with donor sperm (AID) procedure after intra-couple
      intracytoplasmic sperm injection (ICSI) failure offers a significant chance of
      pregnancy and to identify prognostic factors for pregnancy after an AID
      procedure. An eleven-year retrospective multicenter study was conducted among 13
      Centre d'Etude et de Conservation des Oeufs et du Sperme (CECOS) centers. A total
      of 319 couples having undergone an AID procedure after intra-conjugal ICSI
      failure were included in this study; a total of 1,159 AID and 1,011 intra
      conjugal ICSI cycles were performed. Among the prognostics parameters, the parity
      and the embryo quality could not be adequately addressed, therefore the parity
      was not included in the statistical analysis and the embryo quality has been
      presented as preliminary observations. The pregnancy rate per cycle was 12.0%
      (139/1,159) and the overall AID pregnancy rate per couple was 43.6% (139/319).
      Normal or oligoasthenoteratozoospermia (OAT) semen and women aged 34 years or
      above at the time of AID procedure obtained the lowest AID clinical pregnancy
      rate. Azoospermia or cryptozoospermia semen and women aged below 34 years
      obtained the highest AID clinical pregnancy rate. In conclusion, the transition
      to the AID procedure after intra-conjugal ICSI failure allows such couples to
      obtain a pregnancy, however after each ART failure AID transition should be
      proposed according to the woman's age and sperm characteristics. ABBREVIATIONS:
      AID: artificial insemination with donor sperm; ICSI: intracytoplasmic sperm
      injection; CECOS: Centre d'Etude et de Conservation des Oeufs et du Sperme; OAT:
      oligoasthenoteratozoospermia; IVF: in vitro fertilization; ART: artificial
      reproductive technology; beta hCG: beta human chorionic gonadotrophin; SD:
      standard deviation; OR: Odds ratio.

PMID- 29020466
TI  - Improving post-stroke cognitive and behavioral abnormalities by using virtual
      reality: A case report on a novel use of nirvana.
AB  - Cognitive impairment, as well as mood and anxiety disorders, occur frequently in
      patients following stroke. Aim of this study was to evaluate the effects of a
      combined rehabilitative treatment using conventional relaxation and respiratory
      techniques, in a specific rehabilitative virtual environment (by using Bts
      Nirvana). A 58-year-old woman, affected by hemorrhagic stroke, underwent two
      different rehabilitation trainings, including either standard relaxation
      techniques alone in a common clinical setting or the same psychological approach
      in a semi-immersive virtual environment with an augmented sensorial (audio-video)
      and motor feedback (sensory motor-interaction). We evaluated the patient's
      cognitive and psychological profile before and after the two different trainings,
      by using a specific psychometric battery, aimed to assess cognitive status,
      attention processes and to estimate the presence of mood alterations, anxiety and
      coping strategies. Only at the end of the combined approach, we observed a
      significant improvement in attention and memory functions, with a nearly complete
      relief of anxiety symptoms and an improvement in coping strategies. Relaxation
      and respiratory techniques in a semi-immersive virtual reality environment, using
      Bts-Nirvana, may be a promising tool in improving attention process, coping
      strategies, and anxiety in individuals with neurological disorders, including
      stroke.

PMID- 29020467
TI  - Effects of a fractional picosecond 1,064 nm laser for the treatment of dermal and
      mixed type melasma.
AB  - BACKGROUND: Picosecond laser is a novel modality for pigmented skin disorders
      with extremely short pulse duration. Little is known about the effects of the
      picosecond laser in melasma. OBJECTIVE: This study aimed to investigate the
      efficacy of fractional picosecond 1,064 nm laser in melasma treatment. STUDY
      DESIGN: A prospective, randomized, assessor-blinded, intra-individual split face
      comparative study. METHODS: Female subjects with melasma were enrolled and
      received fractional picosecond 1,064 nm laser plus 4% hydroquinone cream on one
      randomly assigned side of the face; the results were compared to the use of
      hydroquinone cream only on the contralateral side. The modified melasma area
      severity index (mMASI) score, melanin index by Mexameter MX18(r), participant
      satisfaction score by quartile rating scale, and the quality of life by the
      dermatology life quality index (DLQI) were evaluated over 12 weeks. RESULTS:
      Thirty female subjects completed the protocol. The mean (+/- standard deviation,
      SD) mMASI score at the 12-week visit was significantly reduced in the picosecond
      laser-treated areas compared to controls (3.52 +/- 1.4 and 4.18 +/- 2.03
      respectively; p = 0.035). No differences were observed in the mean Mexameter
      melanin index, participant satisfaction score, and DLQI score. The observed
      adverse effects included transient mild erythema and mild skin desquamation.
      CONCLUSION: The addition of fractional picosecond 1,064 nm laser to 4%
      hydroquinone was effective and significantly better than 4% hydroquinone alone
      for the treatment of melasma.

PMID- 29020468
TI  - Comparative features of Asthma with frequent or infrequent exacerbations: A
      longitudinal study of retrospective and prospective events.
AB  - BACKGROUND: A "frequent exacerbator phenotype" has been described, mostly in the
      population of patients with severe asthma. Further data are needed on such
      exacerbation-prone patients in milder asthma. AIM: To compare the characteristics
      of frequent and nonfrequent exacerbators in asthma of different severities and to
      assess the stability of the exacerbator status. METHODS: This was an
      observational study comparing baseline data from frequent (>=2 exacerbations in
      the past year) and nonfrequent (<2 exacerbations in the past year) exacerbators.
      Patients were also followed up for one year. Information regarding clinical,
      physiologic, and inflammatory characteristics was collected at baseline and one
      year follow-up. RESULTS: Forty-seven frequent and 53 nonfrequent exacerbators
      were recruited. No specific clinical, physiologic, or inflammatory characteristic
      was observed in the frequent as compared to the nonfrequent exacerbators at
      baseline. Fifty-eight percent of patients reporting frequent exacerbations at
      baseline remained in this group after one year of follow-up. Forty-two and 62% of
      patients with, respectively, mild-to-moderate asthma and severe asthma had
      frequent exacerbations. In a post hoc analysis according to asthma severity,
      frequent exacerbators with severe asthma had a higher body mass index and poorer
      asthma control, although they reported higher adherence to medication, in
      comparison to frequent exacerbators with mild-to-moderate asthma. No specific
      characteristics could discriminate between frequent and nonfrequent exacerbators
      of the same asthma severity. CONCLUSIONS: Frequent exacerbators with severe
      asthma present some specific characteristics not observed in frequent
      exacerbators with mild-to-moderate disease. However, the latter group should be
      identified to reassess treatment needs and potential contributing factors.

PMID- 29020469
TI  - Enabling Student Success for the NBCOT Exam: A Pilot Education Program.
AB  - This piloted asynchronous online course enabled students to prepare for the
      certification examination during the students' second level II clinical
      experience. Instructional strategies included creation of individualized resource
      materials and study plans, weekly assignments, and practice tests' data. A
      comparison of cohorts will be discussed, as well as lessons learned for future
      course development and instructional design that will enable students to learn
      skills required to successfully complete the certification examination.

PMID- 29020470
TI  - Diagnostic Value of Plasma Pentraxin-3 in Acute Appendicitis.
AB  - PURPOSE: To measure serum PTX3 levels in patients admitted with right lower
      quadrant pain to emergency department and to investigate whether this parameter
      will be helpful for the diagnosis of acute appendicitis. MATERIALS AND METHODS:
      This study was conducted with a group of 89 patients over 17 years of age who
      were admitted with the complaint of right lower quadrant pain to ED and had a
      preliminary diagnosis of acute appendicitis clinically and the control group of
      31 healthy volunteers in a tertiary university hospital for 3 months. RESULTS:
      Median PTX3 levels were 3.28 (1.08-30.24) ng/mL in the acute appendicitis groups
      and 0.97 (0.34-2.62) ng/mL in the control group. A significant difference was
      observed between acute appendicitis groups and the control group (p < 0.05).
      CONCLUSION: PTX3 was found to be significantly higher in patient with acute
      appendicitis compared to the control group and the patients with non-specific
      abdominal pain. PTX3 can be used as an aid in the diagnosis of acute
      appendicitis.

PMID- 29020471
TI  - Culture-Positive Endogenous Endophthalmitis: An Eleven-Year Retrospective Study
      in the Central Region of Thailand.
AB  - PURPOSE: To report the characteristics of infection and prognostic factors of
      endogenous endophthalmitis (EE) over an 11-year period. METHODS: The clinical
      records of 41 eyes of 36 patients diagnosed with culture-proven EE at the
      Rajavithi Hospital were retrospectively reviewed. RESULTS: Median age at
      presentation was 58 years. Liver abscess (19%) and urinary tract infections (19%)
      were the most common sources of infection. The most common causative agents were
      gram-negative organisms (48%). The most commonly isolated microorganism was
      Klebsiella pneumoniae (26.8%). Worse initial visual acuity and severe intraocular
      inflammation at first presentation were equally associated with poor visual
      outcome in the multivariate model (adjusted odds ratio, 20.32; 95% confidence
      interval [1.12-357.45]; P = 0.040). CONCLUSIONS: Endogenous endophthalmitis
      usually has a poor visual prognosis. Liver abscess and urinary tract infections
      are common primary sites of infection. Poor initial visual acuity and severe
      intraocular inflammation at the initial presentation are predictors of poor
      visual outcome.

PMID- 29020472
TI  - Effect of transcranial direct current stimulation combined with cognitive
      training on cognitive functioning in older adults with HIV: A pilot study.
AB  - The objective of this study was to examine combination speed of processing (SOP)
      cognitive remediation therapy (CRT) and transcranial direct stimulation (tDCS) as
      neurorehabilitation in older HIV+ adults. Thirty-three HIV+ adults aged 50+
      completed neurocognitive testing and were randomized to either active (n = 17) or
      sham (n = 16) tDCS. Both conditions received 10 1-hour sessions of SOP CRT, with
      either active or sham tDCS for the first 20 minutes. Participants then completed
      a posttest assessment. Repeated measures analysis of variance examining Time X
      Condition showed small-to-medium effects in the expected direction for an
      executive (d = 0.36), and SOP measure (d = 0.49), while medium-to-large effects
      were observed for an executive/attention (d = 0.60) and oral reading measure (d =
      0.75). The only statistically significant interaction was the oral reading
      measure. Small-to-medium and medium-to-large effects (ds = 0.32, 0.58) were found
      for two SOP measures in the opposite direction (sham group showing greater
      improvements). Further trials of CRT and tDCS in this population are needed,
      including larger samples and a nonactive control and tDCS only condition, as is
      determination of which parameters of each technique (e.g., tDCS montage, timing
      of tDCS, domain targeted in CRT, number of sessions) are most effective in
      improving cognitive outcomes, durability of training gains, and translation to
      everyday functioning.

PMID- 29020473
TI  - Cutis mormorata telangiectatica congenital successfully treated with intense
      pulsed light therapy: A case report.
AB  - Cutis marmorata telangiectatica congenita is a rare disorder characterized by
      cutis marmorata, telangiectasia with or without recurrent ulcerations. It is a
      benign vascular anomaly with dilatation of capillaries and veins in the dermis.
      There is no satisfactory treatment for the ulcerative variety of cutis marmorata
      telangiectatica congenita. In this case, intense pulse light therapy was used
      with almost near total cure. Intense pulse light with its vascular filter of
      wavelength 550-1200 nm was used every fortnight till complete resolution of
      lesions.

PMID- 29020474
TI  - Laser-assisted hair removal for facial hirsutism in women: A review of evidence.
AB  - Poly cystic ovarian syndrome (PCOS) has been described as the common diagnosis
      for hirsutism in women. Facial hirsutism is by far the most distressing symptom
      of hyperandrogenism in women with PCOS. A statistically significant improvement
      in psychological well-being has been reported in patients with PCOS allocated for
      laser-assisted hair removal. The theory of selective photothermolysis has
      revolutionized laser hair removal in that it is effective and safe, when operated
      by sufficiently trained and experienced professionals. Long-pulsed ruby (694 nm),
      long-pulsed alexandrite (755 nm), diode (800-980 nm), and long-pulsed Nd:YAG
      (1064 nm) are commercially available laser devices for hair removal most widely
      studied. This article will introduce the fundamentals and mechanism of action of
      lasers in hair removal, in a contemporary literature review looking at medium to
      long term efficacy and safety profiles of various laser hair removal modalities
      most widely commercially available to date.

PMID- 29020475
TI  - Association of khellin and 308-nm excimer lamp in the treatment of severe
      alopecia areata in a child.
AB  - Alopecia areata (AA) is an autoimmune inflammatory disorder of hair,
      characterized by non-scarring hair loss. A 308-nm excimer lamp (EL) has been
      reported as one effective modality in the treatment of AA. Khellin is a
      furanochromone photosensitizer whose chemical structure is close to psoralens and
      has previously proven its efficacy in vitiligo in association with ultraviolet A.
      We evaluated the efficacy and safety of a combination of topical khellin and 308
      nm EL in the treatment of a refractory ophiasic AA, of 1-year evolution, in a 5
      year-old boy. Treatment consisted in topical application of khellin 45 mn before
      irradiation with EL (starting dose 50 mJ/cm2) twice a week for 3 months. The
      result was a complete regrowth of hair with no recurrence 1 year later. Further
      studies should be carried out to confirm this promising result and to propose
      khellin-excimer as a new alternative treatment for resistant cases of AA in
      children.

PMID- 29020476
TI  - Adulteration and Counterfeiting of Online Nutraceutical Formulations in the
      United States: Time for Intervention?
AB  - Global prevalence of nutraceuticals is noticeably high. The American market is
      flooded with nutraceuticals claiming to be of natural origin and sold with a
      therapeutic claim by major online retail stores such as Amazon and eBay. The
      objective of this commentary is to highlight the possible problems of online-sold
      nutraceuticals in the United States with respect to claim, adulterants, and
      safety. Furthermore, there is a lack of strict regulatory laws governing the
      sales, manufacturing, marketing, and label claims of nutraceutical formulations
      currently sold in the U.S. market. Major online retail stores and Internet
      pharmacies aid the widespread sale of nutraceuticals. Finally, according to the
      literature, many of these products were found to be either counterfeit or
      adulterated with active pharmaceutical ingredients (API) and mislabeled as being
      safe and natural. Therefore, regulatory authorities along with the research
      community should intervene to draw attention to these products and their possible
      effects.

PMID- 29020477
TI  - Quality of Life and Psychological Aspects in Patients with Visual Impairment
      Secondary to Uveitis: A Clinical Study in a Tertiary Care Hospital in Brazil.
AB  - PURPOSE: To evaluate the quality of life in individuals with bilateral visual
      impairment secondary to uveitis and its association with sociodemographic,
      clinical and psychosocial aspects. METHODS: Data were collected through a
      structured interviews, using four forms; the SF-12v2, HADS, NEI-VFQ-25 and a
      specific form developed to collect clinical and sociodemographic data. RESULTS:
      80 patients were included with a mean age of 42.8 years; 63.8% female; 57.5% with
      permanent reduction of familiar income. The average number of medical visits was
      15.2 +/-10.7/year. In terms of health-related quality of life (HRQol), the mean
      of VFQ-25 score was 36.6 +/- 15.1 and the mean of SF-12 physical and mental
      components scores were 43.3 +/- 9.9 and 44.9 +/- 12.2. Anxiety and depression
      symptoms were found in 65.1% and 32.5% of patients, respectively. CONCLUSIONS:
      Visual impairment has impact on several scales of HRQoL leading to productivity
      loss and consumption of health resources.

PMID- 29020478
TI  - Photobiomodulation therapy for androgenetic alopecia: A clinician's guide to home
      use devices cleared by the Federal Drug Administration.
AB  - : The market for home-use photobiomodulation devices to treat androgenetic
      alopecia has rapidly expanded, and the Food and Drug Administration (FDA) has
      recently cleared many devices for this purpose. Patients increasingly seek the
      advice of dermatologists regarding the safety and efficacy of these hair loss
      treatments. The purpose of this guide was threefold: (1) to identify all home-use
      photobiomodulation therapy devices with FDA-clearance for treatment of
      androgenetic alopecia; (2) to review device design, features and existing
      clinical evidence; and (3) to discuss practical considerations of
      photobiomodulation therapy, including patient suitability, treatment goals,
      safety, and device selection. A search of the FDA 510(k) Premarket Notification
      database was conducted using product code "OAP" to identify all home-use devices
      that are FDA-cleared to treat androgenetic alopecia. Thirteen commercially
      available devices were identified and compared. Devices varied in shape,
      wavelength, light sources, technical features, price, and level of clinical
      evidence. To date, there are no head-to-head studies comparing the efficacy of
      these devices. Photobiomodulation therapy devices have an excellent safety
      profile and mounting evidence supporting their efficacy. However, long-term, high
      quality studies comparing these devices in diverse populations are lacking. As
      these devices become increasingly popular, dermatologists should be familiar with
      this treatment modality to add to their therapeutic armamentarium. ABBREVIATIONS:
      AGA, androgenetic alopecia; FDA, Food and Drug Administration; IEC, International
      Electrotechnical Commission; LED, light-emitting diode; PBMT, photobiomodulation
      therapy.

PMID- 29020480
TI  - Bilateral Hemorrhagic Retinopathy with Roth Spots in Pediatric-Onset Systemic
      Lupus Erythematosus and Associated Thrombocytopenia: A Case Report and Review of
      Literature.

PMID- 29020479
TI  - Silicone gel enhances the efficacy of Er:YAG laser treatment for atrophic acne
      scars: A randomized, split-face, evaluator-blinded, placebo-controlled,
      comparative trial.
AB  - BACKGROUND: The effect of topical silicone gel has been studied to prevent scars
      from burn, postoperative wound and to treat hypertrophic scars. No previous
      studies have been done to evaluate the efficacy of topical silicone gel on
      atrophic acne scars. MATERIAL AND METHODS: Nineteen patients were treated with
      three sessions of ablative Er:YAG laser with 1-month intervals. Following each
      laser treatment, the randomlyassigned silicone gel or placebo was applied in
      split-face manner. Objective assessments, which included roughness, smoothness,
      hydration, transepidermal water loss were measured at baseline and prior to each
      treatment. Subjective assessments by dermatologists and subjects were done at
      baseline and 1 month after last laser treatment. RESULTS: The laser treatments
      were well tolerated and resulted in clinical improvements. Topical silicone gel
      treatment resulted in significantly less roughness at weeks 4 and 12 compared
      with placebo (p < 0.05). CONCLUSION: Adding topical silicone gel to ablative
      Er:YAG laser treatment may provide additional benefits in improving acne scars.

PMID- 29020481
TI  - Ocular Toxoplasmosis in Tropical Areas: Analysis and Outcome of 190 Patients from
      a Multicenter Collaborative Study.
AB  - PURPOSE: To describe clinical findings and outcomes for ocular toxoplasmosis in
      an international multicenter collaborative study. METHODS: Retrospective analysis
      of 190 patients diagnosed with ocular toxoplasmosis from three study sites
      (Brazil, India, and Singapore). RESULTS: There were 93 (48.9%) females with a
      mean age of 32.8 years. The most common symptoms were isolated blurring of vision
      (36.8%), followed by blurring of vision with floaters (21.1%). Treatment regimens
      varied largely from monotherapy to multiple combination therapies. Final visual
      acuity of >=20/40 was achieved in 106 (74.2%) patients. In a median follow-up
      period of 31 weeks (range 12-749 weeks), 83/190 (43.7%) patients suffered a
      relapse. CONCLUSIONS: There appears to be geographical variation in the
      presentation of ocular toxoplasmosis. Compared to previous studies, we did not
      observe the '"dual peak" phenomenon of chronic and active disease based on age at
      presentation, and there was less bilateral and macular involvement (but more
      peripheral involvement).

PMID- 29020482
TI  - A retrospective analysis of the influencing factors and complications of Q
      switched lasers in tattoo removal in China.
AB  - BACKGROUND AND OBJECTIVE: Q-switched (QS) lasers are the gold standard for tattoo
      removal. The purpose of the present study was to gain a more comprehensive
      understanding of the factors that influence the efficacy of QS lasers and their
      associated complications in the removal of tattoos in China. PATIENTS AND
      METHODS: Clinical data of 266 patients were analyzed retrospectively. The tattoo
      clearance rate was evaluated using the 4-point scale. The Cox regression model
      was applied to analyze the factors that affected the efficacy of QS lasers in
      tattoo removal. In addition, treatment-related adverse reactions were analyzed.
      RESULTS: The results showed that several variables had a statistically
      significant effect (p < 0.05) on the efficacy of QS laser-mediated tattoo removal
      treatment, including the patients' age, the tattoo's age, type, color, or ink
      density and the number of treatments. A variety of adverse responses occurred
      during the laser treatment. The overall incidence of adverse responses was
      approximately 24.06%, including pigmentation, hypopigmentation, bulla formation,
      allergic reactions, and skin texture changes or hypertrophic scarring.
      CONCLUSION: Some factors may influence the efficacy of QS lasers in the treatment
      of tattoos and certain adverse reactions may occur during this process.

PMID- 29020483
TI  - Efficacy of low-level laser therapy as an auxiliary tool for management of acute
      side effects of head and neck radiotherapy.
AB  - INTRODUCTION: Head and neck radiotherapy (HNRT) is associated with acute and
      chronic side effects, some of which result in great morbidity. The aim of this
      study was to determine the efficacy of low-level laser therapy (LLLT) as an oral
      care tool for the management of these effects. MATERIALS AND METHODS: Clinical
      information was collected from 216 patients undergoing HNRT; these individuals
      were divided into a control group without laser therapy (n = 108) and a laser
      group (n = 108). The intervention of the laser group was performed in a different
      period to the control group and was applied three times weekly. All data were
      analyzed by a descriptive statistical analysis. RESULTS: The presence and
      severity of mucositis were similar between the groups. However, the laser group
      showed a lower frequency of interruption of oncologic therapy related to
      mucositis (p = 0.030) and the need of nasogastric tube nutrition during the HNRT
      (p = 0.027). In addition, trismus was less intense in the laser group (p =
      0.023). CONCLUSIONS: The introduction of laser therapy in the supportive care for
      patients undergoing HNRT showed benefits for the patient and the medical system,
      reducing morbidity and costs associated with side-effects.

PMID- 29020484
TI  - Long-term outcome of a patient with paradoxical hypertrichosis after laser
      epilation.
AB  - One underreported, rare side effect of laser hair removal is paradoxical
      hypertrichosis. It is largely unknown what the long-term outcomes are of patients
      who develop this complication. We report a 21-year-old, Fitzpatrick II, male
      patient, who had patchy areas of dark hair affecting various body areas. An
      Alexandrite 755 nm laser was used to address the desired areas at energies
      between 20 and 22 J/cm2 at 10-12-week intervals over a course of seven
      treatments. After three treatments, the patient noted a significant increase in
      the density and length of hairs involving the back, shoulders, neck, and upper
      arms. The patient was followed on a biannual basis, without further epilatory
      intervention. After 10 years, the areas of paradoxical hair growth were sparser
      compared to immediate post-treatment but remained denser compared to pre
      treatment. This case illustrates improvement in the condition over time without
      intervention. Further studies are needed to determine the etiopathogenesis of
      this phenomenon.

PMID- 29020485
TI  - Comment on: "Intravitreal Injection of Sulfamethoxazole and Trimethoprim
      Associated with Dexamethasone as an Alternative Therapy for Ocular
      Toxoplasmosis".

PMID- 29020486
TI  - Ocular Manifestations and Visual Outcomes of Behcet's Uveitis in a Thai
      population.
AB  - PURPOSE: To report on ocular manifestations and visual outcomes of Thai patients
      with Behcet's Uveitis (BU). METHODS: We reviewed medical records of 50 BU
      patients (31 males and 19 females). Ocular manifestations, treatment modalities,
      complications, and visual outcomes were registered. RESULTS: Ocular involvement
      was bilateral in 76% of patients, resulting in 89 affected eyes. Panuveitis and
      posterior uveitis were the most common types. Retinal vasculitis was noted in
      majority of affected eyes and specifically arteritis was noticed in 32/57(56%).
      Most patients received combination therapy of systemic corticosteroids and
      immunosuppressive agents (azathioprine 72%). At final visit, VA <=20/200 was
      observed in 25 affected eyes (28%). Risk factors for poor visual outcome were
      poor visual acuity at presentation (p < 0.001) and development of optic atrophy
      (p = 0.01). CONCLUSIONS: Typical ocular manifestations of Thai patients with BU
      consisted of bilateral uveitis affecting posterior eye segment with high rate of
      complications and frequent visual loss.

PMID- 29020487
TI  - Clinical Characteristics and Prognostic Factors in Ankylosing Spondylitis
      Associated Uveitis.
AB  - PURPOSE: To identify the clinical features and prognostic factors of uveitis
      associated with ankylosing spondylitis (AS). METHODS: This retrospective,
      interventional case series study reviewed the medical records of 91 AS patients
      with uveitis. RESULTS: The characteristics of AS-associated uveitis included male
      preponderance (70%), average onset in the fourth decade, unilateral manifestation
      (87.9%), and vitreous involvement or retinal vascular leakage (36.3%). All
      patients had acute anterior uveitis. The best corrected visual acuity in logMAR
      improved from 0.8 +/- 0.3 to 0.1 +/- 0.2. The use of biologic agents was the only
      significant factor in the multivariate analysis. Patients with vitreous
      involvement/retinal vascular leakage were more likely to use systemic/peribulbar
      steroids for inflammation control, and achieved equally favorable visual outcome
      as in those without vitreous involvement/retinal vascular leakage. CONCLUSION:
      The clinical characteristics and profile of visual prognostic factors suggest an
      association between the severity of ocular inflammation and systemic disease.

PMID- 29020488
TI  - Unilateral Ocular Manifestations of Vogt-Koyanagi-Harada Disease.
AB  - PURPOSE: To describe a case of unilateral Vogt-Koyanagi-Harada (VKH) disease and
      associated multimodal imaging. METHODS: Retrospective case report. RESULTS: A 50
      year-old Hispanic male presented with three days of painless decreased vision in
      his left eye, headache, and decreased hearing. His visual acuity was 20/20 in the
      right eye and counting fingers in the left eye. Examination of his right eye was
      unremarkable. Funduscopic examination of his left eye revealed multiple serous
      retinal detachments. Fluorescein angiography demonstrated late multifocal
      pinpoint hyperfluorescence in his left eye and a diagnosis of VKH disease was
      made. He was treated with oral prednisone. Serial re-examination demonstrated
      resolution of the serous retinal detachments and a taper of his oral prednisone
      was initiated with improvement of his visual acuity to 20/25. CONCLUSIONS: Our
      patient had imaging and a clinical course that was consistent with VKH disease.
      This unilateral presentation may represent a clinical variant of VKH disease.

PMID- 29020489
TI  - Multiple Evanescent White Dot Syndrome following Acute Epstein-Barr Virus
      Infection.
AB  - PURPOSE: To investigate the association between multiple evanescent white dot
      syndrome (MEWDS) and Epstein-Barr (EB) virus infection. METHODS: A prospective,
      consecutive case series study was performed in patients with the characteristic
      findings of MEWDS. Patients received EB viral-specific antibody serologic tests.
      RESULTS: Five cases of MEWDS who had prodromal flu-like symptoms were enrolled,
      comprising 2 women and 3 men with a mean age of 34. Mean diopter of myopia was 
      7.5. During acute onset of MEWDS, EB virus infection was confirmed by positive EB
      virus serology test. One showed positive EB viral capsid antigen (EB-VCA) IgM,
      and the other four showed highly elevated titer of EB-VCA IgG more than 1:160.
      Two months later, paired serum virus serology data showed negative EB-VCA IgM, or
      prior EB-VCA IgG titer decreased four-fold in the recovery stage. CONCLUSION:
      MEWDS may be associated with acute systemic EB virus infection. Ocular symptoms
      might develop due to this infection or represent virus-induced autoimmune
      inflammatory retinitis.

PMID- 29020490
TI  - Impact of ticagrelor on P2Y1 and P2Y12 localization and on cholesterol levels in
      platelet plasma membrane.
AB  - Ticagrelor is an antiplatelet agent that inhibits platelet activation via P2Y12
      antagonism. There are several studies showing that P2Y12 needs lipid rafts to be
      activated, but there are few data about how ticagrelor impacts lipid raft
      organization. Therefore, we aimed to investigate how ticagrelor could impact the
      distribution of cholesterol and consequently alter the organization of lipid
      rafts on platelet plasma membranes. We identified cholesterol-enriched raft
      fractions in platelet membranes by quantification of their cholesterol levels.
      Modifications in cholesterol and protein profiles (Flotillin 1, Flotillin 2,
      CD36, P2Y1, and P2Y12) were studied in platelets stimulated by ADP, treated by
      ticagrelor, or both. In ADP-stimulated and ticagrelor-treated groups, we found a
      decreased level of cholesterol in raft fractions of platelet plasma membrane
      compared to the control group. In addition, the peak of cholesterol in different
      experimental groups changed its localization on membrane fractions. In the
      control group, it was situated on fraction 2, while in ADP-stimulated platelets,
      it was located in fractions 3 to 5, and in fraction 4 in ticagrelor-treated
      group. The proteins studied also showed changes in their level of expression and
      localization in fractions of plasma membrane. Cholesterol levels of plasma
      membranes have a direct role in the organization of platelet membranes and could
      be modified by stimulation or drug treatment. Since ticagrelor and ADP both
      changed lipid composition and protein profile, investigating the lipid and
      protein composition of platelet membranes is of considerable importance as a
      focus for further research in anti-platelet management.

PMID- 29020492
TI  - Comment on Trad et al.'s "Update on Immunological Test (Quantiferon-TB Gold)
      Contribution in the Management of Tuberculosis-Related Ocular Inflammation".

PMID- 29020491
TI  - Ocular Syphilis: An Update.
AB  - This review aims to provide an update on the clinical presentation, diagnosis,
      and treatment of ocular syphilis. While ocular syphilis is not a new phenomenon,
      recent resurgence in the incidence of overall syphilis, particularly among HIV
      positive individuals, has sparked a new interest in an old disease. The challenge
      of ocular syphilis is manifold: firstly, it manifests in a spectrum of ways that
      can occur at any stage of the disease, with the most common finding being
      panuveitis. It may occur as early as 6 weeks after transmission and may be the
      only presenting feature of systemic syphilis; secondly, the relationship between
      HIV and syphilis has been established, as primary syphilis facilitates HIV
      transmission and HIV may modify the natural course of syphilis, increasing the
      propensity of the disease to progress to neurosyphilis. The authors present the
      latest updates to the changing landscape of ocular syphilis.

PMID- 29020493
TI  - Authors reply to Letter to the Editor-In response to: "Tripathy, K. Update on
      Immunological Test (Quantiferon-TB Gold) Contribution in the Management of
      Tuberculosis-Related Ocular Inflammation".

PMID- 29020494
TI  - Comment on Durrani et al.'s "Adalimumab for Ocular Inflammation".

PMID- 29020495
TI  - Effect of Adalimumab on Peripheral Blood Mononuclear Cells in Non-Infectious
      Uveitis.
AB  - PURPOSE: This study analyzed the effect of adalimumab on peripheral blood
      mononuclear cells (PBMCs) in uveitis. METHODS: PBMCs and serum S100A12 levels
      from 14 uveitis patients and 28 healthy controls were analyzed. Patient samples
      were taken before (w0), and 6 (w6) and 12 (w12) weeks after initiation of
      adalimumab therapy. RESULTS: Monocytes expressing CD124, CD86, CD39, CD115, and
      MHCII were decreased in patients. Adalimumab induced CD86+ and CD39+ monocytes,
      and further decreased the frequency of MHCII- and CD124-positive cells. Patients
      (w0) had increased percentages of Th1-, Th17-, and Th2 cells and T cell subsets
      showed a pro-inflammatory polarization (p = 0.02 ratio Th17/Treg patients w0 vs
      controls), which was reduced upon adalimumab treatment (p = 0.05 w0 vs w6).
      S100A12 levels were increased in patients (p = 0.02) and reduced under treatment
      (p = 0.02 for w6/w12). CONCLUSIONS: The phenotype of PBMCs from uveitis patients
      is modified upon adalimumab treatment. Serum S100A12 levels reflect the systemic
      immune response.

PMID- 29020496
TI  - Clinical Outcomes of Adjunctive Sustained-Release Intravitreal Dexamethasone
      Implants in Tuberculosis-Associated Multifocal Serpigenoid Choroiditis.
AB  - PURPOSE: To analyze the safety and efficacy of sustained-release intravitreal
      dexamethasone implant (Ozurdex) in management of TB-associated multifocal
      serpiginoid choroiditis (MSC). METHODS: Retrospective review of TB-associated MSC
      patients, treated with anti-TB therapy (ATT) and adjunctive intravitreal Ozurdex.
      RESULTS: Nine eyes of six patients were included. Four patients required Ozurdex
      implant for progressive or new lesions following ATT and two for additional
      systemic contraindications to corticosteroids - hyperglycemia and uncontrolled
      hypertension, respectively. The mean time to resolution was 9.17 +/- 7.71 weeks.
      The mean follow-up post-injection was 13.11 +/- 6.05 months (median 12 months
      [range 6-24.5 months]). Only one of nine eyes developed recurrent MSC lesions and
      this was attributed to possible autoimmune etiology. Two eyes (22.2%) developed
      steroid-induced glaucoma - one required implant removal. CONCLUSIONS: Sustained
      release intravitreal dexamethasone is a safe and efficacious adjunctive anti
      inflammatory therapy for TB-associated MSC patients with contraindication for
      systemic corticosteroids or requiring supplemental anti-inflammatory therapy.

PMID- 29020497
TI  - Stimuli-Responsive Nanodiamond-Based Biosensor for Enhanced Metastatic Tumor Site
      Detection.
AB  - Metastasis is often critical to cancer progression and linked to poor survival
      and drug resistance. Early detection of metastasis, as well as identification of
      metastatic tumor sites, can improve cancer patient survival. Thus, developing
      technology to improve the detection of cancer metastasis biomarkers can improve
      both diagnosis and treatment. In this study, we investigated the use of
      nanodiamonds to develop a stimuli-responsive metastasis detection complex that
      utilizes matrix metalloproteinase 9 (MMP9) as a metastasis biomarker, as MMP9
      increased expression has been shown to be indicative of metastasis. The
      nanodiamond-MMP9 biosensor complex consists of nanodiamonds functionalized with
      MMP9-specific fluorescent-labeled substrate peptides. Using this design, protease
      activity of MMP9 can be accurately measured and correlated to MMP9 expression.
      The nanodiamond-MMP9 biosensor also demonstrated an enhanced ability to protect
      the base sensor peptide from nonspecific serum protease cleavage. This enhanced
      peptide stability, combined with a quantitative stimuli-responsive output
      function, provides strong evidence for the further development of a nanodiamond
      MMP9 biosensor for metastasis site detection. More importantly, this work
      provides the foundation for use of nanodiamonds as a platform for stimuli
      responsive biosensors and theranostic complexes that can be implemented across a
      wide range of biomedical applications.

PMID- 29020500
TI  - Tocilizumab for the Treatment of Behcet Uveitis that Failed Interferon Alpha and
      Anti-Tumor Necrosis Factor-Alpha Therapy.
AB  - PURPOSE: To report the results of tocilizumab (TCZ) treatment in patients with
      Behcet uveitis (BU) who had failed conventional, interferon alpha, and anti-Tumor
      necrosis factor-alpha therapy. METHODS: We reviewed the records of five patients
      with BU treated with monthly infusions of TCZ 8 mg/kg. Outcome measures were
      visual acuity, anterior chamber cells, laser flare meter (LFM) readings, vitreous
      haze, central macular thickness (CMT), and fluorescein angiography (FA) score.
      RESULTS: The clinical inactivity of BU and 20/50 or better vision were achieved
      in three female and two male patients treated with TCZ for 5-19 months. The mean
      LFM reading was reduced from 15.4 +/- 2.7 to 5.0 +/- 0.9 ph/ms; the mean CMT from
      324.7 +/- 36.6 um to 280.2 +/- 34.1 um; and the mean FA score from 20.6 +/- 5.4
      to 9.3 +/- 4.5 um at the last visit. The only side effect was a slight elevation
      of the total cholesterol level in one patient. CONCLUSIONS: Tocilizumab may be a
      safe and effective therapeutic option for refractory BU.

PMID- 29020499
TI  - Chikungunya Virus Infection Associated with Encephalitis and Anterior Uveitis.
AB  - Chikungunya virus (CHIKV) is an RNA virus transmitted by Aedes mosquitoes. The
      clinical manifestations include fever, arthralgia, rash, and other atypical
      clinical findings including ocular lesions. We report the case of a 57-year-old
      man with meningoencephalitis and anterior uveitis due to CHIKV. The patient had
      developed bilateral anterior uveitis with iris atrophy and a cotton wool spot on
      the left eye, and his serum, urine, saliva, and cerebrospinal fluid were positive
      for CHIKV by RT-PCR. The spectrum of the ophthalmologic manifestations and its
      pathophysiology in cases of CHIKV infections needs to be better understood.
      Additional studies examining the ocular lesions caused by CHIKV could improve the
      therapeutic goals of reducing the morbidity and sequels.

PMID- 29020498
TI  - LncRNA CCAT1/miR-130a-3p axis increases cisplatin resistance in non-small-cell
      lung cancer cell line by targeting SOX4.
AB  - BACKGROUND: Colon cancer-associated transcript-1 (CCAT1) has been demonstrated to
      act as an oncogene and promote chemoresistance in several cancers. However,
      little is known about the underlying mechanism of CCAT1 in cisplatin (DDP)
      resistance of non-small-cell lung cancer (NSCLC) cells. METHODS: qRT-PCR was
      performed to detect the expression levels of CCAT, miR-130a-3p, or sex
      determining region Y-box 4 (SOX4) mRNA. Luciferase reporter assay, RNA
      immunoprecipitation (RIP), and qRT-PCR analysis were carried out to explore the
      potential targets of CCAT1 or miR-130a-3p. Effect of CCAT1, miR-130a-3p, or SOX4
      on IC50 value of DDP and ATP binding cassette subfamily G member 2 (ABCG2) level
      in NSCLC cells were determined by cell counting kits-8 (CCK-8) assay and western
      blot, respectively. RESULTS: CCAT1 and SOX4 were up-regulated, and miR-130a-3p
      was down-regulated in DDP-resistant NSCLC cells compared with their parental
      NSCLC cells. CCAT1 directly interacted with miR-130a-3p and negatively regulated
      miR-130a-3p expression. CCAT1 contributed to DDP resistance of A549/DDP cells by
      down-regulating miR-130a-3p. miR-130a-3p was found to directly target SOX4 to
      suppress its expression. SOX4 knockdown reversed miR-130a-3p-inhibition-induced
      increase of DDP resistance and ABCG2 expression in NSCLC cells. Exogenous
      expression of SOX4 abrogated CCAT1-knockdown-mediated decrease of DDP resistance
      and ABCG2 expression in DDP-resistant NSCLC cells. CONCLUSION: CCAT1/miR-130a-3p
      axis enhanced DDP resistance of NSCLC cells by targeting SOX4, providing
      potential targets to overcome DDP resistance and improve efficacy of chemotherapy
      for patients with NSCLC.

PMID- 29020501
TI  - Ultra-Wide Field Imaging in Paradoxical Worsening of Tubercular Multifocal
      Serpiginoid Choroiditis after the Initiation of Anti-Tubercular Therapy.
AB  - PURPOSE: To evaluate role of ultra-wide field (UWF) versus conventional imaging
      in the follow-up and paradoxical worsening (PW) of tubercular (TB) multifocal
      serpiginoid choroiditis (MSC). METHODS: Prospective observational study of
      patients with TB MSC undergoing UWF imaging, autofluorescence and fluorescein
      angiography was performed. A circle simulating central 75 degrees  field
      representing conventional imaging was drawn on UWF images. The information
      yielded by the two modalities, progression of choroiditis lesions and PW was
      compared. RESULTS: 44 eyes (29 patients, mean age: 30.7 +/- 9 years; 23 males)
      were included. UWF imaging showed additional lesions in 39/44 eyes (88.6%).
      Overall, 16/44 eyes (36.4%) showed PW; 3/16 eyes (18.7%) showed only peripheral
      PW, while 10/16 eyes showed both central and peripheral PW. Management was
      altered in 11 patients (37.93%) based on UWF imaging. CONCLUSIONS: UWF is more
      useful than conventional imaging in identifying additional choroiditis lesions,
      PW and altering the course of therapy in TB MSC.

PMID- 29020503
TI  - High-Throughput Screening for Protein Synthesis Inhibitors Targeting Aminoacyl
      tRNA Synthetases.
AB  - Aminoacylation has been implicated in a wide variety of cancers. Aminoacyl-tRNA
      synthetases (ARSs) exist in large excess in tumor cells due to their increased
      demand for translation, whereas most other protein-synthesis apparatuses are
      quantitatively limited. Among other components that constitute the translation
      machinery-namely, tRNA, amino acid, ATP, and ARS-ARS is the only target that can
      be blocked by small molecules. No constitutively active ARSs have been reported,
      and mutations of ARS can cause inaccurate substrate recognition and malformation
      of the multi-ARS complex (MSC). Hence, interference of the activity is expected
      to be independent of genotype without developing resistance. Here, we report a
      high-throughput screening (HTS) system to find mammalian ARS inhibitors. The
      rabbit-reticulocyte lysate we used closely resembles both the individual and
      complexed structures of human ARSs, and it may predispose active compounds that
      are readily applicable for humankind. This assay was further validated because it
      identified familiar translational inhibitors from a pilot screen, such as
      emetine, proving its suitability for our purpose. The assay demonstrated
      excellent quality control (QC) parameters and reproducibility, and is proven
      ready for further HTS campaigns with large chemical libraries.

PMID- 29020502
TI  - Persistence of DNA adducts, hypermutation and acquisition of cellular resistance
      to alkylating agents in glioblastoma.
AB  - Glioblastoma is a lethal form of brain tumour usually treated by surgical
      resection followed by radiotherapy and an alkylating chemotherapeutic agent. Key
      to the success of this multimodal approach is maintaining apoptotic sensitivity
      of tumour cells to the alkylating agent. This initial treatment likely
      establishes conditions contributing to development of drug resistance as
      alkylating agents form the O6-methylguanine adduct. This activates the mismatch
      repair (MMR) process inducing apoptosis and mutagenesis. This review describes
      key juxtaposed drivers in the balance between alkylation induced mutagenesis and
      apoptosis. Mutations in MMR genes are the probable drivers for alkylation based
      drug resistance. Critical to this interaction are the dose-response and temporal
      interactions between adduct formation and MMR mutations. The precision in dose
      interval, dose-responses and temporal relationships dictate a role for alkylating
      agents in either promoting experimental tumour formation or inducing tumour cell
      death with chemotherapy. Importantly, this resultant loss of chemotherapeutic
      selective pressure provides opportunity to explore novel therapeutics and
      appropriate combinations to minimise alkylation based drug resistance and tumour
      relapse.

PMID- 29020504
TI  - Fibrocartilage Stem Cells Engraft and Self-Organize into Vascularized Bone.
AB  - Angiogenesis is a complex, multicellular process that is critical for bone
      development and generation. Endochondral ossification depends on an avascular
      cartilage template that completely remodels into vascularized bone and involves a
      dynamic interplay among chondrocytes, osteoblasts, and endothelial cells. We have
      discovered fibrocartilage stem cells (FCSCs) derived from the temporomandibular
      joint (TMJ) mandibular condyle that generates cartilage anlagen, which is
      subsequently remodeled into vascularized bone using an ectopic transplantation
      model. Here we explore FCSC and endothelial cell interactions during vascularized
      bone formation. We found that a single FCSC colony formed transient cartilage and
      host endothelial cells may participate in bone angiogenesis upon subcutaneous
      transplantation in a nude mouse. FCSCs produced an abundance of the proangiogenic
      growth factor vascular endothelial growth factor A and promoted the proliferation
      of human umbilical vein endothelial cells (HUVECs). Using a fibrinogen gel bead
      angiogenesis assay experiment, FCSC cell feeder layer induced HUVECs to form
      significantly shorter and less sprouts than D551 fibroblast controls, suggesting
      that FCSCs may initially inhibit angiogenesis to allow for avascular cartilage
      formation. Conversely, direct FCSC-HUVEC contact significantly enhanced the
      osteogenic differentiation of FCSCs. To corroborate this idea, upon
      transplantation of FCSCs into a bone defect microenvironment, FCSCs engrafted and
      regenerated intramembranous bone. Taken together, we demonstrate that the
      interactions between FCSCs and endothelial cells are essential for FCSC-derived
      vascularized bone formation. A comprehensive understanding of the environmental
      cues that regulate FCSC fate decisions may contribute to deciphering the
      mechanisms underlying the role of FCSCs in regulating bone formation.

PMID- 29020506
TI  - Potential application of immobilized streptokinase extracted from Streptococcus
      equinus VIT_VB2.
AB  - Streptokinase purified from Streptococcus equinus VIT_VB2 isolated from bovine
      milk sample was immobilized in various solid supports namely entrapment in
      agarose gel, calcium alginate beads and gelatin gel by cross-linking with
      formaldehyde. Immobilization of streptokinase in calcium alginate beads showed
      maximum efficiency (81.8 +/- 1.06%) when compared with entrapment with agarose
      gel (55.6 +/- 2.17%) and cross-linked gelatin formaldehyde gel (71.0 +/- 1.54%).
      The purified SK activity was expressed maximum in calcium alginate (1%) and
      gelatin gel (0.25%) with 1292.68 +/- 1.33 and 1121.9 +/- 1.2 U mL-1,
      respectively. Similarly, SK entrapped in gelatin gel and calcium alginate showed
      maximum in vitro blood clot lysis activity with 77.67 +/- 2.64% and 76.16 +/-
      2.72%, respectively. The immobilized SK in gelatin gel showed complete clot lysis
      within 15 min; hence, this application of the study could be used in the
      treatment of superficial thrombophlebitis, phlebitis, and venous thrombosis.
      These beads were used for three repeated cycles to check the conversion of
      substrates into their products, and we concluded that SK can be immobilized in
      the suitable matrices. Therefore, this helps in the drug-delivery strategies in
      highly efficient way, moreover, economically competent process in the
      pharmaceutics.

PMID- 29020505
TI  - Socioecological Factors Related to Hazardous Alcohol use among Female Sex Workers
      in Lilongwe, Malawi: A Mixed Methods Study.
AB  - BACKGROUND: Alcohol use is pervasive among female sex workers (FSW) placing them
      at increased risk of violence and sexual risk behaviors. FSW often live and work
      where alcohol is highly normative. OBJECTIVE: To understand the socioecological
      influences on hazardous alcohol use among FSW in Malawi. METHODS: In 2014, 200
      FSW identified through venue-based sampling in Lilongwe, Malawi, completed a
      quantitative behavioral survey, with a sub-sample participating in qualitative
      interviews. Multivariable log-binomial regression was used to identify
      associations between hazardous alcohol use (AUDIT score >= 7) and time in sex
      work, clients per week, unprotected sex, alcohol use with clients, and living
      environment. Qualitative interviews enhanced findings from quantitative data and
      identify emergent themes around socioecological influences on alcohol use.
      RESULTS: Over 50% reported hazardous alcohol use and lived in an alcohol-serving
      venue. Hazardous alcohol use was associated with sex work duration of >=2 years
      (aPR: 1.30; 95%CI: 1.02,1.65) and alcohol use at last sex with a client (aPR:
      1.29; 95%CI: 1.06,1.57). FSW perceived alcohol as a facilitator for sex work by
      reducing inhibitions and attracting clients, but acknowledged alcohol leads to
      violence and/or unprotected sex. Despite these risks and a motivation to reduce
      use, FSW feared that refusing to drink would be tantamount to turning away
      clients. CONCLUSIONS: Although FSW recognized alcohol-related risks, the norms
      and power dynamics of sex work perpetuated hazardous alcohol use. Multilevel
      interventions are needed to collectively change norms around drinking and sex
      work that will enable FSW to reduce alcohol consumption when engaging in their
      work.

PMID- 29020507
TI  - Custom Repair of Mandibular Bone Defects with 3D Printed Bioceramic Scaffolds.
AB  - Implanting artificial biomaterial implants into alveolar bone defects with
      individual shape and appropriate mechanical strength is still a challenge. In
      this study, bioceramic scaffolds, which can precisely match the mandibular
      defects in macro and micro, were manufactured by the 3-dimensional (3D) printing
      technique according to the computed tomography (CT) image. To evaluate the
      stimulatory effect of the material substrate on bone tissue regeneration in situ
      in a rabbit mandibular alveolar bone defect model, implants made with the newly
      developed, mechanically strong ~10% Mg-substituted wollastonite (Ca90%Mg10%SiO3;
      CSi-Mg10) were fabricated, implanted into the bone defects, and compared with
      implants made with the typical Ca-phosphate and Ca-silicate porous bioceramics,
      such as beta-tricalcium phosphate (TCP), wollastonite (CaSiO3; CSi), and
      bredigite (Bred). The initial physicochemical tests indicated that although the
      CSi-Mg10 scaffolds had the largest pore dimension, they had the lowest porosity
      mainly due to the significant linear shrinkage of the scaffolds during sintering.
      Compared with the sparingly dissolvable TCP scaffolds (~2% weight loss) and
      superfast dissolvable (in Tris buffer within 6 wk) pure CSi and Bred scaffolds
      (~12% and ~14% weight loss, respectively), the CSi-Mg10 exhibited a mild in vitro
      biodissolution and moderate weight loss of ~7%. In addition, the CSi-Mg10
      scaffolds showed a considerable initial flexural strength (31 MPa) and maintained
      very high flexural resistance during soaking in Tris buffer. The in vivo results
      revealed that the CSi-Mg10 scaffolds have markedly higher osteogenic capability
      than those on the TCP, CSi, and Bred scaffolds after 16 wk. These results suggest
      a promising potential application of customized CSi-Mg10 3D robocast scaffolds in
      the clinic, especially for repair of alveolar bone defects.

PMID- 29020508
TI  - Variability of intended copies for etanercept (Enbrel(r)): Data on multiple
      batches of seven products.
AB  - Fusion protein and monoclonal antibody-based tumor necrosis factor (TNF)
      inhibitors represent established treatment options for a range of inflammatory
      diseases. Regulatory authorities have outlined the structural characterization
      and clinical assessments necessary to establish biosimilarity of a new
      biotherapeutic product with the innovator biologic drug. Biologic products that
      would not meet the minimum World Health Organization's standard for evaluation of
      similar biotherapeutic products are available in some countries; in some cases
      relevant data to assess biosimilarity and appropriate regulatory approval
      pathways are lacking. Batches of seven intended copy (IC) products for etanercept
      (Enbrel(r)) were subjected to a subset of test methods used in the routine
      release and heightened characterization of Enbrel(r), to determine key attributes
      of identity, quality, purity, strength, and activity. While a number of quality
      attributes of the IC lots tested met the release specifications for Enbrel(r),
      none fell within these limits across all methods performed, and there were no IC
      lots that satisfied the criteria typically applied by the innovator to support
      comparability with Enbrel(r). Although the consequences of these differences are
      largely unknown, the potential for unanticipated clinical outcomes should not be
      overlooked.

PMID- 29020509
TI  - Phylogeny and taxonomy of Echinodontium and related genera.
AB  - The phylogenetic relationship of eight species of Echinodontium, Laurilia, and
      Perplexostereum of Russulales were analyzed based on sequences of the nuc rDNA
      ITS1-5.8S-ITS2 (ITS [internal transcribed spacer]) and D1-D2 domains of nuc 28S
      rDNA (28S). Our results show that Echinodontium tinctorium, E. ryvardenii, and E.
      tsugicola represent Echinodontium sensu stricto. Based on morphological and
      phylogenetic evidence, the new genus Echinodontiellum is established to
      accommodate Echinodontium japonicum. Amylostereum, Echinodontium,
      Echinodontiellum, and Larssoniporia form the Echinodontiaceae clade. The
      Bondarzewiaceae clade includes Bondarzewia, Heterobasidion, Laurilia, and
      Lauriliella. The new genus Lauriliella is established for the species initially
      described as Stereum taxodii and Lauriliella taiwanensis new to science. The
      monotypic genus Perplexostereum forms a distinct clade. A key to the genera in
      the Echinodontiaceae and Bondarzewiaceae as well to Perplexostereum is provided.

PMID- 29020510
TI  - Secretory expression and enzymatic characterization of recombinant Agarivorans
      albus beta-agarase in Escherichia coli.
AB  - Agarase catalyzes the hydrolysis of agar, which is primarily used as a medium for
      microbiology, various food additives, and new biomass materials. In this study,
      we described the expression of the synthetic gene encoding beta-agarase from
      Agarivorans albus (Aabeta-agarase) in Escherichia coli. The synthetic beta
      agarase gene was designed based on the biased codons of E. coli to optimize its
      expression and extracellular secretion in an active, soluble form. The
      synthesized agarase gene, including its signal sequence, was cloned into the pET
      26 expression vector, and the pET-Aabeta-agarase plasmid was introduced into E.
      coli BL21-Star (DE3) cells. The E. coli transformants were cultured for high
      yield secretion of recombinant Aabeta-agarase in Luria-Bertani broth containing
      0.6 mM isopropyl beta-D-1-thiogalactopyranoside for 9 h at 37 degrees C. The
      expressed recombinant Aabeta-agarase was purified by ammonium sulfate
      precipitation and diethylaminoethyl-sepharose column chromatography, yielding ~10
      mg/L Aabeta-agarase. The purified recombinant Aabeta-agarase exhibited optimal
      activity at pH 7 and 40 degrees C, and its activity was strongly inhibited by
      Cu2+, Mn2+, Zn2+, and Al3+ ions. Furthermore, the KM and kcat values for purified
      Aabeta-agarase were ~0.02 mM and ~45/s, respectively. These kinetic values were
      up to approximately 15-100-fold lower than the KM values reported for other
      agarases and approximately 7-30-fold higher than the kcat/KM values reported for
      other agarases, indicating that recombinant Aabeta-agarase exhibited good
      substrate-binding ability and high catalytic efficiency. These results
      demonstrated that the E. coli expression system was capable of producing
      recombinant Aabeta-agarase in an active form, at a high yield, and with
      attributes useful in the relevant industries.

PMID- 29020511
TI  - Bayesian additive decision trees of biomarker by treatment interactions for
      predictive biomarker detection and subgroup identification.
AB  - Personalized medicine, or tailored therapy, has been an active and important
      topic in recent medical research. Many methods have been proposed in the
      literature for predictive biomarker detection and subgroup identification. In
      this article, we propose a novel decision tree-based approach applicable in
      randomized clinical trials. We model the prognostic effects of the biomarkers
      using additive regression trees and the biomarker-by-treatment effect using a
      single regression tree. Bayesian approach is utilized to periodically revise the
      split variables and the split rules of the decision trees, which provides a
      better overall fitting. Gibbs sampler is implemented in the MCMC procedure, which
      updates the prognostic trees and the interaction tree separately. We use the
      posterior distribution of the interaction tree to construct the predictive scores
      of the biomarkers and to identify the subgroup where the treatment is superior to
      the control. Numerical simulations show that our proposed method performs well
      under various settings comparing to existing methods. We also demonstrate an
      application of our method in a real clinical trial.

PMID- 29020512
TI  - Enhanced alpha-amylase production by a marine protist, Ulkenia sp. using response
      surface methodology and genetic algorithm.
AB  - Amylases are a group of enzymes with a wide variety of industrial applications.
      Enhancement of alpha-amylase production from the marine protists,
      thraustochytrids has been attempted for the first time by applying statistical
      based experimental designs using response surface methodology (RSM) and genetic
      algorithm (GA) for optimization of the most influencing process variables. A full
      factorial central composite experimental design was used to study the cumulative
      interactive effect of nutritional components viz., glucose, corn starch, and
      yeast extract. RSM was performed on two objectives, that is, growth of Ulkenia
      sp. AH-2 (ATCC(r) PRA-296) and alpha-amylase activity. When GA was conducted for
      maximization of the enzyme activity, the optimal alpha-amylase activity was found
      to be 71.20 U/mL which was close to that obtained by RSM (71.93 U/mL), both of
      which were in agreement with the predicted value of 72.37 U/mL. Optimal growth at
      the optimized process variables was found to be 1.89A660nm. The optimized medium
      increased alpha-amylase production by 1.2-fold.

PMID- 29020513
TI  - Application of an integrated Weather Research and Forecasting (WRF)/CALPUFF
      modeling tool for source apportionment of atmospheric pollutants for air quality
      management: A case study in the urban area of Benxi, China.
AB  - : In this study, the authors endeavored to develop an effective framework for
      improving local urban air quality on meso-micro scales in cities in China that
      are experiencing rapid urbanization. Within this framework, the integrated
      Weather Research and Forecasting (WRF)/CALPUFF modeling system was applied to
      simulate the concentration distributions of typical pollutants (particulate
      matter with an aerodynamic diameter <10 MUm [PM10], sulfur dioxide [SO2], and
      nitrogen oxides [NOx]) in the urban area of Benxi. Statistical analyses were
      performed to verify the credibility of this simulation, including the
      meteorological fields and concentration fields. The sources were then categorized
      using two different classification methods (the district-based and type-based
      methods), and the contributions to the pollutant concentrations from each source
      category were computed to provide a basis for appropriate control measures. The
      statistical indexes showed that CALMET had sufficient ability to predict the
      meteorological conditions, such as the wind fields and temperatures, which
      provided meteorological data for the subsequent CALPUFF run. The simulated
      concentrations from CALPUFF showed considerable agreement with the observed
      values but were generally underestimated. The spatial-temporal concentration
      pattern revealed that the maximum concentrations tended to appear in the urban
      centers and during the winter. In terms of their contributions to pollutant
      concentrations, the districts of Xihu, Pingshan, and Mingshan all affected the
      urban air quality to different degrees. According to the type-based
      classification, which categorized the pollution sources as belonging to the
      Bengang Group, large point sources, small point sources, and area sources, the
      source apportionment showed that the Bengang Group, the large point sources, and
      the area sources had considerable impacts on urban air quality. Finally, combined
      with the industrial characteristics, detailed control measures were proposed with
      which local policy makers could improve the urban air quality in Benxi. In
      summary, the results of this study showed that this framework has credibility for
      effectively improving urban air quality, based on the source apportionment of
      atmospheric pollutants. IMPLICATIONS: The authors endeavored to build up an
      effective framework based on the integrated WRF/CALPUFF to improve the air
      quality in many cities on meso-micro scales in China. Via this framework, the
      integrated modeling tool is accurately used to study the characteristics of
      meteorological fields, concentration fields, and source apportionments of
      pollutants in target area. The impacts of classified sources on air quality
      together with the industrial characteristics can provide more effective control
      measures for improving air quality. Through the case study, the technical
      framework developed in this study, particularly the source apportionment, could
      provide important data and technical support for policy makers to assess air
      pollution on the scale of a city in China or even the world.

PMID- 29020514
TI  - Repair of Iron Centers RIC protein contributes to the virulence of Staphylococcus
      aureus.
AB  - RICs are a family of bacterial proteins involved in the repair of iron centers
      containing proteins damaged by the antimicrobial reactive species liberated by
      the innate immune system of infected hosts. Staphylococcus aureus is a human
      pathogen with increasing antibiotic resistance that also contains a RIC-like
      protein. In this work, we show that the survival of S. aureus within macrophages
      decreases upon inactivation of ric, and that the viability was restored to levels
      similar to the wild-type strain by reintroduction of ric via in trans
      complementation. Importantly, in macrophages that do not produce reactive oxygen
      species, the lower survival of the ric mutant was no longer observed. In lung
      epithelial cells, the intracellular viability of the S. aureus ric mutant was
      also shown to be lower than that of the wild-type. The wax moth larvae Galleria
      mellonella infected with S. aureus ric mutant presented an approximately 2.5
      times higher survival when compared to the wild-type strain. Moreover,
      significantly lower bacterial loads were determined in the larvae hemolymph
      infected with strains not expressing ric, and complementation assays confirmed
      that this behavior was related to RIC. Furthermore, expression of the S. aureus
      ric gene within the larvae increased along the course of infection with a ~20
      fold increase after 8 h of infection. Altogether, the data show that RIC is
      important for the virulence of S. aureus.

PMID- 29020515
TI  - Manufacturing history of etanercept (Enbrel(r)): Consistency of product quality
      through major process revisions.
AB  - Etanercept (ETN) (Enbrel(r)) is a soluble protein that binds to, and specifically
      inhibits, tumor necrosis factor (TNF), a proinflammatory cytokine. ETN is
      synthesized in Chinese hamster ovary cells by recombinant DNA technology as a
      fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of
      human IgG1. Successful manufacture of biologics, such as ETN, requires
      sophisticated process and product understanding, as well as meticulous control of
      operations to maintain product consistency. The objective of this evaluation was
      to show that the product profile of ETN drug substance (DS) has been consistent
      over the course of production. Multiple orthogonal biochemical analyses, which
      included evaluation of attributes indicative of product purity, potency, and
      quality, were assessed on >2,000 batches of ETN from three sites of DS
      manufacture, during the period 1998-2015. Based on the key quality attributes of
      product purity (assessed by hydrophobic interaction chromatography HPLC), binding
      activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell
      based bioassay) and quality (N-linked oligosaccharide map), we show that the
      integrity of ETN DS has remained consistent over time. This consistency was
      maintained through three major enhancements to the initial process of
      manufacturing that were supported by detailed comparability assessments, and
      approved by the European Medicines Agency. Examination of results for all major
      quality attributes for ETN DS indicates a highly consistent process for over 18
      years and throughout changes to the manufacturing process, without affecting
      safety and efficacy, as demonstrated across a wide range of clinical trials of
      ETN in multiple inflammatory diseases.

PMID- 29020516
TI  - Seasonal dynamics and fungicide sensitivity of organisms causing brown patch of
      tall fescue in North Carolina.
AB  - Brown patch, caused by multiple species of Rhizoctonia and Rhizoctonia-like
      fungi, is the most severe summer disease of tall fescue in home lawns across the
      southeastern United States. Home lawns were surveyed in central North Carolina
      from 2013 to 2015 to determine the organisms present during typical epidemics of
      brown patch in tall fescue. Isolates of Rhizoctonia and Rhizoctonia-like fungi
      were obtained by sampling 147 locations in July 2013 and May and July 2014. In
      addition, 11 sites were sampled once a week for 12 consecutive weeks from late
      May to the end of July 2015. All isolates were identified to species and
      anastomosis group with nuc rDNA internal transcribed spacer (ITS) sequence
      analysis. Isolations from brown patch lesions in May 2014 predominately yielded
      Ceratobasidium cereale (77% of the organisms recovered), whereas the organisms
      recovered in July 2013 and 2014 were R. solani AG 2-2-IIIB (44%), R. solani AG 1
      IB (37%), and R. zeae (14%). In 2015, Ceratobasidium cereale was isolated from
      all 11 locations in May but was replaced by Rhizoctonia species in June and July.
      Sensitivity of the May 2014 isolates to multiple concentrations of the fungicides
      azoxystrobin, flutolanil, fluxapyroxad, and propiconazole was compared with
      sensitivity of isolates collected in 2003, to determine whether multiple years of
      exposure to fungicides applied for brown patch control had altered fungicide
      sensitivity. Historical isolates of R. solani, which had never been exposed to
      fungicide applications for brown patch control, were also included for
      comparison. Mean EC50 values (concentration of fungicide needed to inhibit
      mycelial growth by 50%) varied across fungicides and species, but no resistance
      was observed, and there was no apparent shift in sensitivity over the years. An
      additional 94 isolates from 2015 were screened against azoxystrobin, flutolanil,
      fluxapyroxad, and propiconazole, and fungicide insensitivity was not observed.

PMID- 29020517
TI  - Phylogenetic assessment of Chromocyphellaceae (Agaricineae, Basidiomycota) and a
      new lamellate species of Chromocyphella.
AB  - Cyphelloid fungi represent a polyphyletic assemblage of reduced agarics,
      including the brown-spored family Chromocyphellaceae. In order to elucidate the
      phylogenetic position of Chromocyphellaceae, newly generated sequences of
      Chromocyphella were included in a multigene alignment of the Agaricineae and
      phylogenetically analyzed. The current analyses show that the Chromocyphella
      muscicola specimen used to phylogenetically place Chromocyphellaceae in its
      original description was misidentified and that the Chromocyphellaceae nests in
      the Hymenogastraceae, Chromocyphella being sister to Flammula. Chromocyphella is
      emended, including now a new species with lamellate and stipitate basidiomata, C.
      lamellata. The name Cymbella crouanii, type species of Chromocyphella, is lecto-
      and epitypified. Our analyses support a new origin of cyphelloid fungi. The shift
      to a cyphelloid basidioma from an agaric ancestor is suggested to have occurred
      in two evolutionary steps in Chromocyphella, an initial reduction in basidioma
      size and a subsequent loss of lamellae and stipe.

PMID- 29020519
TI  - Emergent is Authentic: A Sociomaterial Perspective on Simulation-Enhanced
      Interprofessional Education.
AB  - This Conversations Starter article presents a selected research abstract from the
      2017 Association of American Medical Colleges Western Region Group on Educational
      Affairs annual spring meeting. The abstract is paired with the integrative
      commentary of three experts who shared their thoughts stimulated by the study.
      The commentary explores the implications of sociomaterial perspectives for
      conceptualizing authenticity in the design and evaluation of simulation-enhanced
      interprofessional education.

PMID- 29020522
TI  - Teaching, Learning, and Performance in the Surgical Workplace: Insights From the
      Examination of Intraoperative Interactions.
AB  - This Conversations Starter article presents a selected research abstract from the
      2017 Association of American Medical Colleges Central Region Group on Educational
      Affairs annual spring meeting. The abstract is paired with the integrative
      commentary of three experts who shared their thoughts stimulated by the study.
      These thoughts explore the value of examining intraoperative interactions among
      attending surgeons and residents for enhancing instructional scaffolding;
      entrustment decision making; and distinguishing teaching, learning, and
      performance in the workplace.

PMID- 29020521
TI  - "Yes, and ..." Exploring the Future of Learning Analytics in Medical Education.
AB  - This Conversations Starter article presents a selected research abstract from the
      2017 Association of American Medical Colleges Northeastern Region Group on
      Educational Affairs annual spring meeting. The abstract is paired with the
      integrative commentary of three experts who shared their thoughts stimulated by
      the study. Commentators brainstormed "what's next" with learning analytics in
      medical education, including advancements in interaction metrics and the use of
      interactivity analysis to deepen understanding of perceptual, cognitive, and
      social learning and transfer processes.

PMID- 29020523
TI  - Actions (Can) Speak Louder Than Words.

PMID- 29020524
TI  - Teachers as Learners: Developing Professionalism Feedback Skills via Observed
      Structured Teaching Encounters.
AB  - This Conversations Starter article presents a selected research abstract from the
      2017 Association of American Medical Colleges Southern Region Group on
      Educational Affairs annual spring meeting. The abstract is paired with the
      integrative commentary of 4 experts who shared their thoughts stimulated by the
      study. These thoughts explore the value of the Observed Structured Teaching
      Encounter in providing structured opportunities for medical students to engage
      with the complexities of providing peer feedback on professionalism.

PMID- 29020527
TI  - EOV Editorial Board page.

PMID- 29020528
TI  - Comments on Jennifer Hoult's "Response to Brand and McEwen (2016) Editorial:
      Advocacy for violations of legal rights is not advocacy for justice."

PMID- 29020526
TI  - Antioxidant and mercury chelating activity of Psidium guajava var. pomifera L.
      leaves hydroalcoholic extract.
AB  - Mercury (Hg) is widely distributed in the environment and is known to produce
      several adverse effects in organisms. The aim of the present study was to examine
      the in vitro antioxidant activity and Hg chelating ability of the hydroalcoholic
      extract of Psidium guajava leaves (HEPG). In addition, the potential protective
      effects of HEPG against Hg(II) were evaluated using a yeast model (Saccharomyces
      cerevisiae). HEPG was found to exert significant antioxidant activity in 2,2
      diphenyl-1-picrylhydrazyl scavenger and inhibition of lipid peroxidation induced
      by Fe(II) assays in a concentration-dependent manner. The extract also exhibited
      significant Hg(II) chelating activity. In yeast, Hg(II) induced a significant
      decrease in cell viability. In contrast, HEPG partially prevented the fall in
      cell viability induced by Hg(II). In conclusion, HEPG exhibited protective
      effects against Hg(II)-mediated toxicity, which may be related to both
      antioxidant and Hg(II)-chelating activities.

PMID- 29020525
TI  - Social Determinants of Adherence to Pulmonary Rehabilitation for Chronic
      Obstructive Pulmonary Disease.
AB  - Adherence to pulmonary rehabilitation (PR) is low. Previous studies have focused
      on clinical predictors of PR completion. We aimed to identify social determinants
      of adherence to PR. A cross-sectional analysis of a database of COPD patients (N
      = 455) in an outpatient PR program was performed. Adherence, a ratio of attended
      to-prescribed sessions, was coded as low (<35%), moderate (35-85%), and high
      (>85%). Individual-level measures included age, sex, race, BMI, smoking status,
      pack-years, baseline 6-minute walk distance (6MWD: <150, 150-249, >=250), co
      morbidities, depression, and prescribed PR sessions (<=20, 21-30, >30). Fifteen
      area-level measures aggregated to Census tracts were obtained from the U.S.
      Census after geocoding patients' addresses. Using exploratory factor analysis, a
      neighborhood socioeconomic disadvantage index was constructed, which included
      variables with factor loading >0.5: poverty, public assistance, households
      without vehicles, cost burden, unemployment, and minority population.
      Multivariate regression models were adjusted for clustering on Census tracts.
      Twenty-six percent of patients had low adherence, 23% were moderately adherent,
      51% were highly adherent. In the best fitted full model, each decile increase in
      neighborhood socioeconomic disadvantage increased the risk of moderate vs high
      adherence by 14% (p < 0.01). Smoking tripled the relative risk of low adherence
      (p < 0.01), while each increase in 6MWD category decreased that risk by 72% (p <
      0.01) and 84% (p < 0.001), respectively. These findings show that, relative to
      high adherence, low adherence is associated with limited functional capacity and
      current smoking, while moderate adherence is associated with socioeconomic
      disadvantage. The distinction highlights different pathways to suboptimal
      adherence and calls for tailored intervention approaches.

PMID- 29020529
TI  - Adipose stem cells.

PMID- 29020530
TI  - Doctor, Should I Use Computer Games to Prevent Dementia?
AB  - Commercial advertising of computerized "brain games" may result in clinicians
      being asked whether brain games prevent dementia. To address this question, we
      conducted a review of computerized cognitive training (CCT) interventions in
      older adults with Mild Cognitive Impairment (MCI). Studies were identified using
      a PubMed and PSYCinfo search for review articles. Within 11 review articles we
      identified 15 unique studies. Nine of these studies used commercially available
      "brain games" as their primary CCT intervention. Nine of 12 studies that examined
      the effect of CCT on episodic memory performance showed significant improvements
      in this domain. Furthermore, four of six studies that examined mood and or
      anxiety showed improvements in these domains following a CCT intervention. While
      more than double the amount of time was spent on the training that used
      commercially available "brain games" versus those designed by investigators,
      there were no differences in outcomes. Overall, it appears that "brain games" may
      modestly benefit aspects of cognition and aspects of mood in patients presenting
      with MCI. However, there is no direct evidence from the studies presented here
      that "brain games"/CCT can prevent dementia. We present recommendations to
      consider when discussing "brain games" with persons with MCI.

PMID- 29020531
TI  - Mechanisms of antibiotic resistance in bacteria mediated by silver nanoparticles.
AB  - Silver nanoparticles (AgNPs) are widely used in industry, consumer products, and
      medical appliances due to their efficient antimicrobial properties. However,
      information on environmental toxicity and bacterial impact of these particles is
      not completely elucidated. Results showed that AgNPs produced growth inhibition
      and oxidative stress in bacteria Escherichia coli (gram negative) and
      Staphylococcus aureus (gram positive), with half-maximal inhibitory
      concentrations (IC50) of 12 and 7 mg/L, respectively. Surprisingly, bacteria pre
      exposed to sublethal dose of AgNPs exhibited increased resistance toward
      antibiotics (ampicillin and Pen-Strep) with IC50 elevated by 3-13-fold. Further,
      AgNP pre-exposure raised the minimal inhibitory concentration and minimal
      biocidal concentration by two- to eightfold when cells were challenged with
      antibiotics with diverse mechanisms of action (penicillin, chloramphenicol, and
      kanamycin). Interestingly, we found that upon exposure to ampicillin, strains
      pretreated with AgNPs exhibited lower levels of membrane damage and oxidative
      stress, together with elevated levels of intracellular ATP relative to untreated
      cells. Bacterial reverse mutation assay (Ames test) showed that AgNPs are highly
      mutagenic, consistent with further assays demonstrating abiotic reactive oxygen
      species (ROS) generation and intrinsic DNA cleavage activity in vitro of AgNPs.
      Overall, our results suggest that AgNPs enhance bacterial resistance to
      antibiotics by promoting stress tolerance through induction of intracellular ROS.
      Our data suggest potential consequences of incidental environmental exposure of
      bacteria to AgNPs and indicate the need to regulate use and disposal of AgNPs in
      industry and consumer products.

PMID- 29020533
TI  - Choroidal Structural Changes in Tubercular Multifocal Serpiginoid Choroiditis.
AB  - PURPOSE: To assess choroidal vascular changes among patients with tubercular
      multifocal serpiginoid choroiditis (TB MSC) using previously validated
      techniques. METHODS: Patients with TB MSC (n = 18) and healthy controls (n = 30)
      underwent enhanced-depth imaging optical coherence tomography (EDI-OCT) imaging.
      Using previously validated algorithm of image binarization, EDI-OCT scans were
      segmented to derive total choroidal area, luminal area, stromal area, and
      choroidal vascularity index (CVI). RESULTS: There was a statistically significant
      difference in the CVI between controls (66.90 +/- 1.77%) and TB MSC patients
      (65.46 +/- 2.53%; p < 0.001). There was significant reduction in CVI at follow-up
      (3 months) (63.77 +/- 3.91%; p = 0.05). The choroidal thickness was higher in TB
      MSC compared to controls (278.90 +/- 57.84 um versus 329.33 +/- 27.69 um; p =
      0.001). CONCLUSIONS: CVI provides insight into structural changes in choroid in
      TB MSC. During the active disease, there is relative decrease in choroidal
      vascularity. As the lesions heal, choriocapillaris atrophy occurs with remodeling
      of choroid.

PMID- 29020534
TI  - Extent of Resection in Glioblastoma.

PMID- 29020532
TI  - Trends in point-of-sale tobacco marketing around college campuses: Opportunities
      for enhanced tobacco control efforts.
AB  - OBJECTIVE: Colleges have implemented policies to limit tobacco use on-campus;
      however, the off-campus environment is often overlooked in tobacco control
      efforts. We assessed availability, marketing, and promotion of cigarettes, snus,
      and traditional smokeless tobacco (SLT) in a sample of communities surrounding 11
      college campuses in North Carolina and Virginia. PARTICIPANTS: Between January
      March of 2011, 2012 and 2013, 481 tobacco-selling retailers, including
      convenience stores, pharmacies and supermarkets, located near campuses were
      assessed. METHODS: Trained observers completed annual point-of-sale assessments.
      RESULTS: The percentage of stores selling (81.4% to 58.6%; p < .0001) and
      advertising snus (80.1% to 53.11%; p < .0001) significantly decreased over time.
      Convenience stores increased promotions of cigarettes (65.4% to 72.8%; p = 0.04)
      and SLT (3.1% to 23.3%; p = 0.02). CONCLUSIONS: Off-campus environments have
      abundant tobacco availability and marketing. Colleges should collaborate with
      state and local tobacco control advocates to address tobacco promotion near
      campuses to potentially decrease product appeal and access among young adults.

PMID- 29020535
TI  - Treatment of Glioblastoma.
AB  - Glioblastoma is the most common and most aggressive form of primary brain tumor
      in adults and contributes to high social and medical burden as a result of its
      incurable nature and significant neurologic morbidity. Despite ongoing research,
      there has not been improvement in survival in glioblastoma. This review discusses
      recent advances in clinically significant molecular profiling, including IDH
      mutation status and O6-methylguanine-DNA methyltransferase ( MGMT) promoter
      methylation. We review updates in management of newly diagnosed and recurrent
      glioblastoma, as well as common difficulties in management, such as
      pseudoprogression and pseudoresponse. Ongoing translational research in targeted
      therapy and immunotherapy is briefly discussed.

PMID- 29020536
TI  - Novel Considerations in the Approach to Glioblastoma.

PMID- 29020537
TI  - Challenges of Diagnosing Viral Anterior Uveitis.
AB  - The viral causes of anterior uveitis (AU) emerged with the use of novel molecular
      diagnostic tests and serologic tests adapted for small volumes (Goldmann-Witmer
      Coefficient). The viral causes of AU may be underestimated, and some of the
      presumed idiopathic AU cases will probably be proven to be of viral origin in the
      coming years. So far, a viral origin of AU was suspected in patients who
      presented with unilateral hypertensive AU. It is not clear which clinical
      presentations should raise a suspicion of viral etiology. There is an overlap in
      the clinical manifestations of AU caused by viruses and other non-viral forms of
      AU. A viral cause of AU should be suspected in patients with unilateral AU,
      exhibiting small or medium sized KPs, some form of iris atrophy, high IOP and
      early development of a cataract and the definitive diagnosis can be proven by
      aqueous humor analysis.

PMID- 29020538
TI  - Orbital Inflammatory Syndrome Post Group A Streptococcal Infection - Case Series
      and Review of Literature.
AB  - OBJECTIVE: To report new cases of orbital inflammatory syndrome (OIS) post group
      A streptococcal (GAS) infection and review the literature. METHODS: A
      retrospective case series of patients with OIS post GAS infection seen in our
      clinic (from January 2015 to December 2016) and review of additional patients
      from the literature. RESULTS: A total of nine patients with OIS post GAS
      infection were included in the study (four patients seen in our clinic and five
      from previous literature); seven females and two males, three children (under the
      age of 16), and six adults. Eight patients (89%) presented with a single rectus
      muscle (5 medial, 3 lateral) myositis, and one (11%) presented with posterior
      scleritis and diffuse OIS. CONCLUSIONS: Although there are very few reports on
      OIS post GAS infection, it may be more common than previously thought and should
      be considered in the differential diagnosis of patients with orbital
      inflammation.

PMID- 29020539
TI  - The Exposure Effects of Online Model Pictures and Weight-Related Persuasive
      Messages on Women's Weight-Loss Planned Behaviors.
AB  - This study examined how exposure to pictures of women with different body sizes
      (thin, obese), physical attractiveness levels (attractive, unattractive), along
      with exposure to weight-related messages (pro-anorexia, anti-anorexia) embedded
      in a fashion website affected female participants' planned behavior toward weight
      loss. Participants exposed to attractive model pictures showed higher intentions,
      attitudes, and subjective norms to lose weight compared with unattractive models.
      Additionally, participants exposed to thin and attractive model pictures
      indicated the highest attitudes and self-efficacy to lose weight, whereas those
      exposed to thin and unattractive model pictures indicated the lowest.
      Furthermore, weight-related messages moderated the effect of model appearance
      (body size and attractiveness) on controllability of weight-loss activities.
      However, website pictures' body size differences had no main effects on planned
      behavior toward weight loss. These effects are discussed in the light of social
      comparison mechanisms.

PMID- 29020540
TI  - A Trial to Test a Novel Approach to Diabetes Prevention.

PMID- 29020541
TI  - Can We Breathe Easy If PAP Therapy Is Withheld?

PMID- 29020542
TI  - Fairness and Transparency in an Expanded Access Program: Allocation of the Only
      Treatment for SMA1.

PMID- 29020543
TI  - Hard Choices for Vulnerable Patients: Some Lessons Learned That May Apply.

PMID- 29020544
TI  - Is There a 'Right to Try' Experimental Therapies? Ethical Criteria for Selecting
      Patients With Spinal Muscular Atrophy to Receive Nusinersen in an Expanded Access
      Program.

PMID- 29020545
TI  - The Paywall as Metaphor and Symptom.

PMID- 29020546
TI  - The Human Right to Enjoy the Benefits of the Progress of Science and Its
      Applications.

PMID- 29020547
TI  - Imagining Truly Open Access Bioethics: From Dreams to Reality.

PMID- 29020548
TI  - Land-Locked Developing Countries and Their Infrastructural Challenges in
      Contributing to Global Ethics: A Zimbabwe Case Study.

PMID- 29020549
TI  - A Call for Open Access and Empathy Is Not Enough: Hands on Are Needed!

PMID- 29020550
TI  - Global Bioethics and Scientific Sanction.

PMID- 29020551
TI  - Justice and Bioethics: Who Should Finance Academic Publishing?

PMID- 29020552
TI  - Response to Open Peer Commentaries on "Saving Life, Limb, and Eyesight: Assessing
      the Medical Rules of Eligibility During Armed Conflict".

PMID- 29020553
TI  - Physician-Soldier: Navigating the Tension Between Military and Medical Necessity.

PMID- 29020554
TI  - Is It Ethically Acceptable to Screen Patients for Obstructive Sleep Apnea and Not
      Offer Them Positive Air Pressure Therapy in a Clinical Trial?

PMID- 29020555
TI  - A Care Ethics Approach to Medical Eligibility in Armed Conflict.

PMID- 29020556
TI  - How to Enhance Engagement in Bioethics in the Developing World for Global
      Bioethics.

PMID- 29020557
TI  - Risks of Clinical Research Must Be Reasonable and Necessary.

PMID- 29020558
TI  - A Multifaceted Approach Is Needed to Respond to the Plight of Bioethicists in
      Accessing Literature.

PMID- 29020559
TI  - Biopolitics, Pseudoscience, and Bioethics in the Global South.

PMID- 29020560
TI  - Expanded Access for Nusinersen in Patients With Spinal Muscular Atropy:
      Negotiating Limited Data, Limited Alternative Treatments, and Limited Hospital
      Resources.

PMID- 29020561
TI  - Saving Life, Limb, and Eyesight: Assessing the Medical Rules of Eligibility
      During Armed Conflict.
AB  - Medical rules of eligibility permit severely injured Iraqi and Afghan nationals
      to receive care in Coalition medical facilities only if bed space is available
      and their injuries result directly from Coalition fire. The first rule favors
      Coalition soldiers over host-nation nationals and contradicts the principle of
      impartial, needs-based medical care. To justify preferential care for
      compatriots, wartime medicine invokes associative obligations of care that favor
      friends, family, and comrades-in-arms. Associative obligations have little place
      in peacetime medical care but significantly affect wartime medicine. The second
      rule suggests liability for collateral harm that is unsupported by international
      law and military ethics. Absent liability, there are pragmatic reasons to offer
      medical care to injured local civilians if it quells resentment and cements
      support for Coalition forces. In contrast to peacetime medicine, military
      necessity and associative obligations outweigh distributive principles based on
      medical need during war.

PMID- 29020562
TI  - A Question of Social Justice: How Policies of Profit Negate Engagement of
      Developing World Bioethicists and Undermine Global Bioethics.
AB  - We identify the ways the policies of leading international bioethics journals
      limit the participation of researchers working in the resource-constrained
      settings of low- and middle-income countries (LMICs) in the development of the
      field of bioethics. Lack of access to essential scholarly resources makes it
      extremely difficult, if not impossible, for many LMIC bioethicists to learn from,
      meaningfully engage in, and further contribute to the global bioethics discourse.
      Underrepresentation of LMIC perspectives in leading journals sustains the
      hegemony of Western bioethics, limits the presentation of diverse moral visions
      of life, health, and medicine, and undermines aspirations to create a truly
      "global" bioethics. Limited attention to this problem indicates a lack of empathy
      and moral imagination on the part of bioethicists in high-income countries,
      raises questions about the ethics of bioethics, and highlights the urgent need to
      find ways to remedy this social injustice.

PMID- 29020563
TI  - Responsibility for Collateral Harm.

PMID- 29020564
TI  - Can Bioethics Journals Become Role Models in Making Information, Data, Opinion,
      and Cross-Cultural Discussions Universally Available?

PMID- 29020565
TI  - Social Justice in Scholarly Publishing: Open Access Is the Only Way.

PMID- 29020566
TI  - Corrigendum.

PMID- 29020567
TI  - Research Ethics, Military Medical Ethics, and the Challenges of International
      Law.

PMID- 29020568
TI  - Associative Duties and Professional Obligations.

PMID- 29020569
TI  - Does Wartime Bioethics Really Triumph Over Peacetime Bioethics?

PMID- 29020570
TI  - Two-dimensional Solutions in a Multi-dimensional World? A Commentary on "Effect
      of Touch Screen Tablet Use on Fine Motor Development of Young Children".

PMID- 29020572
TI  - Variability in the primary emissions and secondary gas and particle formation
      from vehicles using bioethanol mixtures.
AB  - : Bioethanol for use in vehicles is becoming a substantial part of global energy
      infrastructure because it is renewable and some emissions are reduced. Carbon
      monoxide (CO) emissions and total hydrocarbons (THC) are reduced, but there is
      still controversy regarding emissions of nitrogen oxides (NOx), aldehydes, and
      ethanol; this may be a concern because all these compounds are precursors of
      ozone and secondary organic aerosol (SOA). The amount of emissions depends on the
      ethanol content, but it also may depend on the engine quality and ethanol origin.
      Thus, a photochemical chamber was used to study secondary gas and aerosol
      formation from two flex-fueled vehicles using different ethanol blends in
      gasoline. One vehicle and the fuel used were made in the United States, and the
      others were made in Brazil. Primary emissions of THC, CO, carbon dioxide (CO2),
      and nonmethane hydrocarbons (NMHC) from both vehicles decreased as the amount of
      ethanol in gasoline increased. NOx emissions in the U.S. and Brazilian cars
      decreased with ethanol content. However, emissions of THC, CO, and NOx from the
      Brazilian car were markedly higher than those from the U.S. car, showing high
      variability between vehicle technologies. In the Brazilian car, formation of
      secondary nitrogen dioxide (NO2) and ozone (O3) was lower for higher ethanol
      content in the fuel. In the U.S. car, NO2 and O3 had a small increase. Secondary
      particle (particulate matter [PM]) formation in the chamber decreased for both
      vehicles as the fraction of ethanol in fuel increased, consistent with previous
      studies. Secondary to primary PM ratios for pure gasoline is 11, also consistent
      with previous studies. In addition, the time required to form secondary PM is
      longer for higher ethanol blends. These results indicate that using higher
      ethanol blends may have a positive impact on air quality. IMPLICATIONS: The use
      of bioethanol can significantly reduce petroleum use and greenhouse gas emissions
      worldwide. Given the extent of its use, it is important to understand its effect
      on urban pollution. There is a controversy on whether there is a reduction or
      increase in PM emission when using ethanol blends. Primary emissions of THC, CO,
      CO2, NOx, and NMHC for both cars decreased as the fraction of ethanol in gasoline
      increased. Using a photochemical chamber, the authors have found a decrease in
      the formation of secondary particles and the time required to form secondary PM
      is longer when using higher ethanol blends.

PMID- 29020573
TI  - New species of Talaromyces isolated from maize, indoor air, and other substrates.
AB  - Talaromyces strains isolated from maize seeds and the built environment were
      examined taxonomically because they could not be identified as previously
      described species. Using phenotypic analysis, DNA sequencing, and phylogenetic
      and concordance analyses, the authors discovered and described 10 new species in
      sect. Islandici and 1 new species in sect. Subinflati. Taxonomic novelties in
      sect. Islandici are Talaromyces delawarensis, T. herodensis, T. juglandicola, T.
      kilbournensis, T. novojersensis, T. ricevillensis, T. rogersiae, T. siglerae, T.
      subtropicalis, and T. tiftonensis, and the species from sect. Subinflata is T.
      tzapotlensis. The isolate of T. siglerae is unusual in Talaromyces because it
      produced a Sagenomella-like anamorph, but phylogenetic analysis placed it in
      Talaromyces. Talaromyces rotundus is known from a few isolates, but searches with
      internal transcribed spacer (ITS) sequences in GenBank revealed that it is
      commonly endolichenous with Lasallia hispanica. Talaromyces wortmannii also has a
      role as an endophyte of the aquatic plant Persicaria amphibia, based on ITS
      sequence records from GenBank.

PMID- 29020574
TI  - Suicidal and Help-Seeking Behaviors Among Youth in an Online Lesbian, Gay,
      Bisexual, Transgender, Queer, and Questioning Social Network.
AB  - LGBTQ youth have a great burden for suicidal ideation/behavior compared to their
      non-LGBTQ peers. While scholars have explored risk factors for suicidal
      behaviors, little is known about protective factors among LGBTQ youth, let alone
      within group differences in terms of help-seeking. Data were collected from 203
      TrevorSpace (e.g., a social network for LGBTQ youth) users via online survey to
      examine suicidal and help-seeking behaviors among LGBTQ individuals. Among
      participants who reported suicidal ideation/behavior, a large proportion did not
      seek help (73.1% of gay men, 33.3% of bisexual men, 42.9% of bisexual women,
      14.3% of lesbian women, 41.2% of queer individuals) when they considered or
      attempted suicide. Among those who sought support, reaching out to a friend was
      most common. However, family support was associated with fewer suicidal
      behaviors. Our findings underscore the need to examine the effectiveness of
      specific sources of help and the impact of exposure to social connectedness.

PMID- 29020575
TI  - Possible Selves in Adolescence: Development and Validation of a Scale for their
      Assessment.
AB  - Possible selves (PSs) have a significant role in adolescents' development. For
      this reason, it is of great importance to have adequate measures to
      operationalize them. The aim of this work is to present the construction and
      validation of a scale to assess PSs at the end of high school in multiple
      domains. Participants were adolescents (n = 320) of both sexes (female = 51.3%)
      from high-schools in Buenos Aires City, Argentina (age, M = 14.9, SD = 1.5). The
      scale was developed based on a literature review and a previous qualitative
      study. Expert judges' assessment revealed that it has good content validity. The
      scale's structure was studied with exploratory factor analysis and a 5-factor
      structure with theoretical meaning was found. Spearman's correlations between
      current and future self-perceptions show evidence of convergent validity. Mann
      Whitney U test shows that the scale can discriminate by sex and age. The scale
      shows adequate to very good internal consistency. These results show that the
      scale has adequate psychometric properties to assess PSs in Argentine
      adolescents. The advantages of this scale relative to existing measures of PSs
      are discussed. Scale development allows us to know more about how adolescents
      think they will be during a significant life transition such as the end of high
      school. This is particularly important for planning interventions that focus on
      motivation and behavior regulation.

PMID- 29020576
TI  - Two Special Sections: Addictions and Substance Use & Aging and Social and
      Economic Justice.

PMID- 29020571
TI  - Factors and molecules that could impact cell differentiation in the embryo
      generated by nuclear transfer.
AB  - Somatic cell nuclear transfer is a technique to create an embryo using an
      enucleated oocyte and a donor nucleus. Nucleus of somatic cells must be
      reprogrammed in order to participate in normal development within an enucleated
      egg. Reprogramming refers to the erasing and remodeling of cellular epigenetic
      marks to a lower differentiation state. Somatic nuclei must be reprogrammed by
      factors in the oocyte cytoplasm to a rather totipotent state since the
      reconstructed embryo must initiate embryo development from the one cell stage to
      term. In embryos reconstructed by nuclear transfer, the donor genetic material
      must respond to the cytoplasmic environment of the cytoplast and recapitulate
      this normal developmental process. Enucleation is critically important for
      cloning efficiency because may affect the ultrastructure of the remaining
      cytoplast, thus resulting in a decline or destruction of its cellular
      compartments. Nonetheless, the effects of in vitro culturing are yet to be fully
      understood. In vitro oocyte maturation can affect the abundance of specific
      transcripts and are likely to deplete the developmental competence. The
      epigenetic modifications established during cellular differentiation are a major
      factor determining this low efficiency as they act as epigenetic barriers
      restricting reprogramming of somatic nuclei. In this review we discuss some
      factors that could impact cell differentiation in embryo generated by nuclear
      transfer.

PMID- 29020577
TI  - Hospital Quality and Hospital Value-Based Purchasing.

PMID- 29020578
TI  - Hospital Quality and Hospital Value-Based Purchasing.

PMID- 29020580
TI  - Calcium Oxalate Crystals in Ethylene Glycol Toxicity.

PMID- 29020579
TI  - Delirium in Hospitalized Older Adults.

PMID- 29020581
TI  - CD55 Deficiency and Protein-Losing Enteropathy.

PMID- 29020582
TI  - CD55 Deficiency and Protein-Losing Enteropathy.

PMID- 29020585
TI  - Health Effects of Overweight and Obesity in 195 Countries.

PMID- 29020584
TI  - Health Effects of Overweight and Obesity in 195 Countries.

PMID- 29020586
TI  - Misdirections in Informed Consent - Impediments to Health Care Innovation.

PMID- 29020583
TI  - Glecaprevir and Pibrentasvir in Patients with HCV and Severe Renal Impairment.
AB  - BACKGROUND: Chronic hepatitis C virus (HCV) infection is more prevalent among
      patients who have chronic kidney disease than among those who do not have the
      disease. Patients with chronic kidney disease who also have HCV infection are at
      higher risk for progression to end-stage renal disease than those who have
      chronic kidney disease without HCV infection. Patients with both HCV infection
      and advanced chronic kidney disease have limited treatment options. METHODS: We
      conducted a multicenter, open-label, phase 3 trial to evaluate the efficacy and
      safety of treatment with the combination of the NS3/4A protease inhibitor
      glecaprevir and the NS5A inhibitor pibrentasvir for 12 weeks in adults who had
      HCV genotype 1, 2, 3, 4, 5, or 6 infection and also had compensated liver disease
      (with or without cirrhosis) with severe renal impairment, dependence on dialysis,
      or both. Patients had stage 4 or 5 chronic kidney disease and either had received
      no previous treatment for HCV infection or had received previous treatment with
      interferon or pegylated interferon, ribavirin, sofosbuvir, or a combination of
      these medications. The primary end point was a sustained virologic response 12
      weeks after the end of treatment. RESULTS: Among the 104 patients enrolled in the
      trial, 52% had genotype 1 infection, 16% had genotype 2 infection, 11% had
      genotype 3 infection, 19% had genotype 4 infection, and 2% had genotype 5 or 6
      infection. The sustained virologic response rate was 98% (102 of 104 patients;
      95% confidence interval, 95 to 100). No patients had virologic failure during
      treatment, and no patients had a virologic relapse after the end of treatment.
      Adverse events that were reported in at least 10% of the patients were pruritus,
      fatigue, and nausea. Serious adverse events were reported in 24% of the patients.
      Four patients discontinued the trial treatment prematurely because of adverse
      events; three of these patients had a sustained virologic response. CONCLUSIONS:
      Treatment with glecaprevir and pibrentasvir for 12 weeks resulted in a high rate
      of sustained virologic response in patients with stage 4 or 5 chronic kidney
      disease and HCV infection. (Funded by AbbVie; ClinicalTrials.gov number,
      NCT02651194 .).

PMID- 29020587
TI  - Carotid Sinus Massage.

PMID- 29020588
TI  - Case 31-2017. A 19-Month-Old Girl with Failure to Thrive.

PMID- 29020590
TI  - Crisis in the Sustainability of the U.S. Blood System.

PMID- 29020591
TI  - Celiac Disease and Autoimmunity - The Missing Ingredient.

PMID- 29020592
TI  - First FDA Approval Agnostic of Cancer Site - When a Biomarker Defines the
      Indication.

PMID- 29020593
TI  - Air Pollution and Mortality in the Medicare Population.

PMID- 29020594
TI  - Air Pollution and Mortality in the Medicare Population.

PMID- 29020595
TI  - An Early American Smallpox Vaccine Based on Horsepox.

PMID- 29020596
TI  - Voluntary Site Accreditation - Improving the Execution of Multicenter Clinical
      Trials.

PMID- 29020597
TI  - Lingual Papillomas.

PMID- 29020589
TI  - Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia.
AB  - BACKGROUND: The safety and efficacy of vaccines to prevent Ebola virus disease
      (EVD) were unknown when the incidence of EVD was peaking in Liberia. METHODS: We
      initiated a randomized, placebo-controlled, phase 3 trial of the chimpanzee
      adenovirus 3 vaccine (ChAd3-EBO-Z) and the recombinant vesicular stomatitis virus
      vaccine (rVSV?G-ZEBOV-GP) in Liberia. A phase 2 subtrial was embedded to evaluate
      safety and immunogenicity. Because the incidence of EVD declined in Liberia, the
      phase 2 component was expanded and the phase 3 component was eliminated. RESULTS:
      A total of 1500 adults underwent randomization and were followed for 12 months.
      The median age of the participants was 30 years; 36.6% of the participants were
      women. During the week after the administration of vaccine or placebo, adverse
      events occurred significantly more often with the active vaccines than with
      placebo; these events included injection-site reactions (in 28.5% of the patients
      in the ChAd3-EBO-Z group and 30.9% of those in the rVSV?G-ZEBOV-GP group, as
      compared with 6.8% of those in the placebo group), headache (in 25.1% and 31.9%,
      vs. 16.9%), muscle pain (in 22.3% and 26.9%, vs. 13.3%), feverishness (in 23.9%
      and 30.5%, vs. 9.0%), and fatigue (in 14.0% and 15.4%, vs. 8.8%) (P<0.001 for all
      comparisons); these differences were not seen at 1 month. Serious adverse events
      within 12 months after injection were seen in 40 participants (8.0%) in the ChAd3
      EBO-Z group, in 47 (9.4%) in the rVSV?G-ZEBOV-GP group, and in 59 (11.8%) in the
      placebo group. By 1 month, an antibody response developed in 70.8% of the
      participants in the ChAd3-EBO-Z group and in 83.7% of those in the rVSV?G-ZEBOV
      GP group, as compared with 2.8% of those in the placebo group (P<0.001 for both
      comparisons). At 12 months, antibody responses in participants in the ChAd3-EBO-Z
      group (63.5%) and in those in the rVSV?G-ZEBOV-GP group (79.5%) remained
      significantly greater than in those in the placebo group (6.8%, P<0.001 for both
      comparisons). CONCLUSIONS: A randomized, placebo-controlled phase 2 trial of two
      vaccines that was rapidly initiated and completed in Liberia showed the
      capability of conducting rigorous research during an outbreak. By 1 month after
      vaccination, the vaccines had elicited immune responses that were largely
      maintained through 12 months. (Funded by the National Institutes of Allergy and
      Infectious Diseases and the Liberian Ministry of Health; PREVAIL I
      ClinicalTrials.gov number, NCT02344407 .).

PMID- 29020598
TI  - We Can Do Better - Improving Outcomes in the Midst of an Emergency.

PMID- 29020599
TI  - Trial of Tocilizumab in Giant-Cell Arteritis.

PMID- 29020600
TI  - Trial of Tocilizumab in Giant-Cell Arteritis.

PMID- 29020602
TI  - Grass inflorescence architecture and meristem determinacy.
AB  - The grass inflorescence is striking not only for its beauty and diversity, but
      also for its developmental complexity. While models of inflorescence architecture
      have been proposed in both eudicots and grasses, these are inadequate to fully
      explain the complex branching events that occur during the development of the
      grass inflorescence. Key to understanding grass inflorescence architecture is the
      meristem determinacy/indeterminacy decision, which regulates the number of
      branching events that occur. Here we review what has been learned about meristem
      determinacy from grass mutants with defects in inflorescence development. A
      picture is emerging of a complex network of signaling molecules and meristem
      identity factors that interact to regulate inflorescence meristem activity, many
      of which have been modified during crop domestication directly affecting yield
      traits.

PMID- 29020601
TI  - Pioglitazone, a PPARgamma agonist, reduces nicotine craving in humans, with
      marginal effects on abuse potential.
AB  - Possibly through their actions upon glia, peroxisome proliferator-activated
      receptor agonists (PPAR) have been shown to alter the abuse potential of
      addictive drugs in several preclinical models. The current study extends this
      research into the human laboratory as the first clinical study into the effects
      of the PPAR gamma agonist, pioglitazone, on the abuse potential of nicotine.
      Heavy smokers were recruited for this 3-week study. Upon admission, participants
      were randomized to either active (45mg, n=14) or placebo (0mg, n=13) PIO
      maintenance conditions for the duration of the study. After 5-7days of
      stabilization on a 7mg nicotine patch, participants began laboratory testing. On
      the 1st-4th test days, participants could self-administer cigarettes or receive
      money by making verbal choices for either option. On the 5th day, participants
      were administered 10 puffs of their usual brand of cigarette in the morning and
      later chose between smoking and money by making finger presses on a computer
      mouse in a progressive ratio self-administration task. Later on the 5th day
      participants also underwent a smoking cue exposure session. The 8th-11th test
      days were identical to the 1st-4th test days with the exception that during one
      of the test weeks de-nicotinized cigarettes were available, and during the other
      nicotinized cigarettes were available. Nicotinized cigarettes were always
      administered on the 5th and 12th days. On some measures PIO increased indicators
      of abuse potential, though this effect was typically not statistically
      significant. However, PIO did significantly reduce measures of craving.

PMID- 29020603
TI  - Transcriptional analysis of the putative glycosyltransferase gene (amv248) of the
      Amsacta moorei entomopoxvirus.
AB  - Amsacta moorei entomopoxvirus (AMEV), the most studied member of the genus
      Betaentomopoxvirus, was initially isolated from Red Hairy caterpillar larvae,
      Amsacta moorei. According to genome sequence and previous studies it was shown
      that amv248 encodes a putative glycosyltransferase that is the only conserved
      attachment protein in betaentomopoxviruses. Transcriptional analysis of the
      amv248 gene by RT-PCR and qPCR showed that transcription starts at 6h post
      infection (hpi). Also, transcription was not affected by a DNA replication
      inhibitor but was severely curtailed by a protein synthesis inhibitor. These
      results indicate that amv248 belongs to the intermediate class of gene
      expression. 5' and 3' untranslated regions analysis revealed that transcription
      initiates at position -126 relative to the translational start site, and ends
      between 50 and 83 bases after the stop codon. To narrow down the size and
      location of the gene's promoter, the upstream region as well as several different
      sized deletions thereof were generated and cloned upstream of a luciferase
      reporter gene. The constructs were used to measure the Firefly and Renilla
      luciferase activities in dual assays. The results showed that luciferase activity
      decreased when bases -198 to -235 of amv248 upstream region were missing.
      Sequence analysis among the intermediate gene promoters of AMEV showed that
      TTTAT(T/A)TT(T/A)2TTA is possibly a common motif, however, further investigations
      are needed to confirm this conclusion.

PMID- 29020604
TI  - Predictors of favourable outcome after in-hospital cardiac arrest treated with
      extracorporeal cardiopulmonary resuscitation: A systematic review and meta
      analysis.
AB  - AIMS: To identify the predictors of survival to discharge in adults resuscitated
      with extracorporeal cardiopulmonary resuscitation (ECPR) following in-hospital
      cardiac arrest (IHCA). METHODS: MEDLINE and ISI Web of Science were searched for
      eligible studies. Pooled Odds Ratio (OR) and Pooled Mean Difference (PMD) for
      each predictor were calculated. The quality of evidence (QOE) was evaluated
      according to the GRADE guidelines. RESULTS: Eleven studies were included
      totalling 856 patients. Of these, 324 (37.9%) survived to discharge. Good
      neurological outcome (Cerebral Performance Category 1 or 2) occurred in 222/263
      (84.4%) survivors. Survival was associated with significantly higher odds of an
      initial shockable rhythm (OR 1.65; 95% confidence interval [95%CI] 1.05-2.61;
      p=0.03), shorter low-flow time (PMD -17.15 [-20.90, -13.40]min; p<0.00001), lower
      lactate levels both immediately before ECPR start (PMD -4.12 [-6.0,-2.24]mmol/L;
      p<0.0001) and on ICU admission (PMD -4.13 [-6.38, -1.88]mmol/L; p<0.0003), lower
      SOFA score (PMD -1.71 [-2.93, -0.50]; p=0.006) and lower creatinine levels within
      24h after ICU admission (PMD -0.37 [-0.54, -0.19]mg/dl; p<0.00001). No
      significant association was found between survival and age, gender, or cardiac
      vs. non-cardiac aetiology. The overall QOE was low or very low. CONCLUSIONS: In
      adult IHCA treated with ECPR a shockable initial rhythm, a lower low-flow time,
      lower blood lactate levels before ECPR start or on ICU admission, and a lower
      SOFA score or creatinine levels in the first 24h after ICU admission were
      associated with a higher likelihood of survival. These factors could help
      identifying patients who are eligible for ECPR.

PMID- 29020605
TI  - Cloning and characterization of PHGPx and its synergistic role with p53 in
      mediating stress in Penaeus monodon.
AB  - Phospholipid-hydroperoxide glutathione peroxidase (PHGPx), a ubiquitous
      antioxidant enzyme in the glutathione peroxidase (GPx) family, plays multiple
      roles in different organisms. Here, a novel PHGPx (PmPHGPx) was identified from
      Penaeus monodon. The full-length PmPHGPx cDNA was 1885 bp in length with a 489-bp
      open reading frame (ORF) containing a selenocysteine codon, TGA177-179, and a
      selenocysteine insertion sequence in the 3'-UTR. The typical signature motifs of
      the GPx family were also detected in the PmPHGPx amino acid sequence. The PmPHGPx
      expression pattern showed tissue-specific variations, with the highest expression
      level in the heart and the lowest expression level in the muscle. To examine the
      relationship between Pmp53 and PmPHGPx, Pmp53 was successfully silenced with a
      dsRNA-p53 injection, and an obvious down-regulation in PmPHGPx expression was
      apparent. To clarify the functional roles of Pmp53 and PmPHGPx, their expression
      patterns were also assessed after pH-induced stress, salinity stress and heavy
      metal (Cu, Zn, and Cd) challenges. Similar trends in the expression profiles for
      PmPHGPx and Pmp53 were detected in both the gills and hepatopancreas in response
      to all stressors. Therefore, we conclude from the results that PmPHGPx acts
      synergistically and subsequently works cooperatively with Pmp53 toward mediating
      cell stress. This study improves our understanding of PmPHGPx and its synergistic
      role with Pmp53 in counteracting stressors in P. monodon.

PMID- 29020606
TI  - Using tDCS priming to improve brain function: Can metaplasticity provide the key
      to boosting outcomes?
AB  - Transcranial direct current stimulation (tDCS) has been trialled by many
      researchers attempting to improve brain function. Outcomes have been quite
      variable with seemingly similar protocols yielding either inconsistent or
      insufficiently robust improvements for clinical translation. A potentially
      fruitful avenue for increasing benefits conferred by tDCS stems from findings
      from motor and visual cortex studies that indicate tDCS priming prior to a
      subsequent period of stimulation (tDCS or transcranial magnetic stimulation) can
      in some cases boost outcomes compared to protocols without priming. The
      heightened effects from tDCS priming protocols are thought to be underpinned by
      metaplastic interactions, in which the state induced by the priming influences
      the effects of the second stimulation period. The purpose of the current review
      is to evaluate the potential of tDCS priming protocols to boost outcomes. After
      dissecting the literature, we conclude that although outcomes have varied, tDCS
      priming protocols have demonstrated sufficient promise to warrant attention from
      researchers trying to enhance the efficacy of tDCS.

PMID- 29020608
TI  - Toxicity of Cold Lake Blend and Western Canadian Select dilbits to standard
      aquatic test species.
AB  - Dilbits are blends of bitumen and natural gas condensates or crude oils with only
      limited toxicity data. Two dilbits, Cold Lake Blend and Western Canadian Select,
      were tested as either unweathered or weathered oils for acute and chronic
      toxicity to standard freshwater and estuarine organisms. Water accommodated
      fractions of the dilbits were characterized for total petroleum hydrocarbons
      (TPH), polycyclic aromatic hydrocarbons (PAHs), and monoaromatics (BTEX). Acute
      toxicity of unweathered and weathered dilbits ranged from 4 to 16 mg/L TPH, 8 to
      40 MUg/L total PAHs, and 0.7 to 16 mg/L BTEX in Ceriodaphnia dubia, Pimephales
      promelas, Americamysis bahia, and Menidia beryllina. Concentrations of weathered
      dilbits causing impaired growth (A. bahia) and reproduction (C. dubia) ranged
      from 0.8 to 3.5 mg/L TPH and 6 to 16 MUg/L PAHs. The two dilbits had generally
      similar acute and short term chronic toxicity expressed as TPH or total PAHs as
      other crude oils and other petroleum products.

PMID- 29020609
TI  - Overview of PAT process analysers applicable in monitoring of film coating unit
      operations for manufacturing of solid oral dosage forms.
AB  - Over the last two decades, regulatory agencies have demanded better understanding
      of pharmaceutical products and processes by implementing new technological
      approaches, such as process analytical technology (PAT). Process analysers
      present a key PAT tool, which enables effective process monitoring, and thus
      improved process control of medicinal product manufacturing. Process analysers
      applicable in pharmaceutical coating unit operations are comprehensibly described
      in the present article. The review is focused on monitoring of solid oral dosage
      forms during film coating in two most commonly used coating systems, i.e. pan and
      fluid bed coaters. Brief theoretical background and critical overview of process
      analysers used for real-time or near real-time (in-, on-, at- line) monitoring of
      critical quality attributes of film coated dosage forms are presented. Besides
      well recognized spectroscopic methods (NIR and Raman spectroscopy), other
      techniques, which have made a significant breakthrough in recent years, are
      discussed (terahertz pulsed imaging (TPI), chord length distribution (CLD)
      analysis, and image analysis). Last part of the review is dedicated to novel
      techniques with high potential to become valuable PAT tools in the future
      (optical coherence tomography (OCT), acoustic emission (AE), microwave resonance
      (MR), and laser induced breakdown spectroscopy (LIBS)).

PMID- 29020607
TI  - Epigenetic regulation of motivated behaviors by histone deacetylase inhibitors.
AB  - Growing evidence has begun to elucidate the contribution of epigenetic mechanisms
      in the modulation and maintenance of gene expression and behavior. Histone
      acetylation is one such epigenetic mechanism, which has been shown to profoundly
      alter gene expression and behaviors. In this review, we begin with an overview of
      the major epigenetic mechanisms including histones acetylation. We next focus on
      recent evidence about the influence of environmental stimuli on various motivated
      behaviors through histone acetylation and highlight how histone deacetylase
      inhibitors can correct some of the pathologies linked to motivated behaviors
      including substance abuse, feeding and social attachments. Particularly, we
      emphasize that the effects of histone deacetylase inhibitors on motivated
      behaviors are time and context-dependent.

PMID- 29020610
TI  - Neonatal C57BL/6J and parkin mice respond differently following developmental
      manganese exposure: Result of a high dose pilot study.
AB  - It has been suggested that childhood exposure to neurotoxicants may increase the
      risk of Parkinson's disease (PD) or other neurodegenerative disease in adults.
      Some recessive forms of PD have been linked to loss-of-function mutations in the
      Park2 gene that encodes for parkin. The purpose of this pilot study was to
      evaluate whether responses to neonatal manganese (Mn) exposure differ in mice
      with a Park2 gene defect (parkin mice) when compared with a wildtype strain
      (C57BL/6J). Neonatal parkin and C57BL/6J littermates were randomly assigned to 0,
      11, or 25mg Mn/kg-day dose groups with oral exposures occurring from postnatal
      day (PND) 1 through PND 28. Motor activity was measured on PND 19-22 and 29-32.
      Tissue Mn concentrations were measured in liver, femur, olfactory bulb, frontal
      cortex, and striatum on PND 29. Hepatic and frontal cortex gene expression of
      Slc11a2, Slc40a1, Slc30a10, Hamp (liver only), and Park2 were also measured on
      PND 29. Some strain differences were seen. As expected, decreased hepatic and
      frontal cortex Park2 expression was seen in the parkin mice when compared with
      C57BL/6J mice. Untreated parkin mice also had higher liver and femur Mn
      concentrations when compared with the C57BL/6J mice. Exposure to>=11mg Mn/kg-day
      was associated with increased brain Mn concentrations in all mice, no strain
      difference was observed. Manganese exposure in C57Bl6, but not parkin mice, was
      associated with a negative correlation between striatal Mn concentration and
      motor activity. Manganese exposure was not associated with changes in frontal
      cortex gene expression. Decreased hepatic Slc30a10, Slc40a1, and Hamp expression
      were seen in PND 29 C57BL/6J mice given 25mg Mn/kg-day. In contrast, Mn exposure
      was only associated with decreased Hamp expression in the parkin mice. Our
      results suggest that the Parkin gene defect did not increase the susceptibility
      of neonatal mice to adverse health effects associated with high-dose Mn exposure.

PMID- 29020612
TI  - Covering the Stem Cell Explosion at the 2017 ISSCR Conference in Boston.
AB  - The meeting covered a plethora of rapidly evolving approaches and areas, such as
      organoid cultures modeling tissues and organs; stem cell-specific metabolites
      revealing new signaling pathways; single-cell technologies discovering new cell
      types and exploring stem cell niche interactions; novel methods studying stem
      cells in aging and cancer; lineage-tracing experiments exploring cell plasticity
      of tissues before and after injury; epigenetic studies illuminating cell
      reprogramming; new protocols improving cells for regenerative purposes; and
      several other timely and exciting topics.

PMID- 29020611
TI  - Tubulin-dependent secretion of S100A6 and cellular signaling pathways activated
      by S100A6-integrin beta1 interaction.
AB  - S100A6 is a calcium binding protein expressed mainly in fibroblasts and
      epithelial cells. Interestingly, S100A6 is also present in extracellular fluids.
      Recently we have shown that S100A6 is secreted by WJMS cells and binds to
      integrin beta1 (Jurewicz et al., 2014). In this work we describe for the first
      time the mechanism of S100A6 secretion and signaling pathways activated by the
      S100A6-integrin beta1 complex. We show that colchicine suppressed the release of
      S100A6 into the cell medium, which indicates that the protein might be secreted
      via a tubulin-dependent pathway. By applying double immunogold labeling and
      immunofluorescence staining we have shown that S100A6 associates with
      microtubules in WJMS cells. Furthermore, results obtained from
      immunoprecipitation and proximity ligation assay (PLA), and from in vitro assays,
      reveal that S100A6 is able to form complexes with alpha and beta tubulin in these
      cells, and that the S100A6-tubulin interaction is direct. We have also found that
      the S100A6 protein, due to binding to integrin beta1, activates integrin-linked
      kinase (ILK), focal adhesion kinase (FAK) and p21-activated kinase (PAK). Our
      results suggest that binding of S100A6 to integrin beta1 affects cell
      adhesion/proliferation due to activation of ILK and FAK signaling pathways.

PMID- 29020613
TI  - RNA Exosome Complex-Mediated Control of Redox Status in Pluripotent Stem Cells.
AB  - The RNA exosome complex targets AU-rich element (ARE)-containing mRNAs in
      eukaryotic cells. We identified a transcription factor, ZSCAN10, which binds to
      the promoters of multiple RNA exosome complex subunits in pluripotent stem cells
      to maintain subunit gene expression. We discovered that induced pluripotent stem
      cell clones generated from aged tissue donors (A-iPSC) show poor expression of
      ZSCAN10, leading to poor RNA exosome complex expression, and a subsequent
      elevation in ARE-containing RNAs, including glutathione peroxidase 2 (Gpx2).
      Excess GPX2 leads to excess glutathione-mediated reactive oxygen species
      scavenging activity that blunts the DNA damage response and apoptosis. Expression
      of ZSCAN10 in A-iPSC recovers RNA exosome gene expression, the DNA damage
      response, and apoptosis. These findings reveal the central role of ZSCAN10 and
      the RNA exosome complex in maintaining pluripotent stem cell redox status to
      support a normal DNA damage response.

PMID- 29020616
TI  - The emerging role of follistatin under stresses and its implications in diseases.
AB  - Follistatin (FST), a single-chain glycosylated protein, is expressed in various
      tissues. The essential biological function of FST is binding and neutralizing
      transforming growth factor beta (TGF-beta) superfamily, including activin,
      myostatin, and bone morphogenetic protein (BMP). Emerging evidence indicates that
      FST also serves as a stress responsive protein, which plays a protective role
      under a variety of stresses. In most cases, FST performs the protective function
      through its neutralization of TGF-beta superfamily. However, under certain
      circumstances, FST translocates into the nucleus to maintain cellular homeostasis
      independent of its extracellular antagonism activity. This review provides
      integrated insight into the most recent advances in understanding the role of FST
      under various stresses, and the clinical implications corresponding to these
      findings and discusses the mechanisms to be further studied.

PMID- 29020615
TI  - A Scaled Framework for CRISPR Editing of Human Pluripotent Stem Cells to Study
      Psychiatric Disease.
AB  - Scaling of CRISPR-Cas9 technology in human pluripotent stem cells (hPSCs)
      represents an important step for modeling complex disease and developing drug
      screens in human cells. However, variables affecting the scaling efficiency of
      gene editing in hPSCs remain poorly understood. Here, we report a standardized
      CRISPR-Cas9 approach, with robust benchmarking at each step, to successfully
      target and genotype a set of psychiatric disease-implicated genes in hPSCs and
      provide a resource of edited hPSC lines for six of these genes. We found that
      transcriptional state and nucleosome positioning around targeted loci was not
      correlated with editing efficiency. However, editing frequencies varied between
      different hPSC lines and correlated with genomic stability, underscoring the need
      for careful cell line selection and unbiased assessments of genomic integrity.
      Together, our step-by-step quantification and in-depth analyses provide an
      experimental roadmap for scaling Cas9-mediated editing in hPSCs to study
      psychiatric disease, with broader applicability for other polygenic diseases.

PMID- 29020614
TI  - Gene Editing in Rat Embryonic Stem Cells to Produce In Vitro Models and In Vivo
      Reporters.
AB  - Rat embryonic stem cells (ESCs) offer the potential for sophisticated genome
      engineering in this valuable biomedical model species. However, germline
      transmission has been rare following conventional homologous recombination and
      clonal selection. Here, we used the CRISPR/Cas9 system to target genomic
      mutations and insertions. We first evaluated utility for directed mutagenesis and
      recovered clones with biallelic deletions in Lef1. Mutant cells exhibited reduced
      sensitivity to glycogen synthase kinase 3 inhibition during self-renewal. We then
      generated a non-disruptive knockin of dsRed at the Sox10 locus. Two clones
      produced germline chimeras. Comparative expression of dsRed and SOX10 validated
      the fidelity of the reporter. To illustrate utility, live imaging of dsRed in
      neonatal brain slices was employed to visualize oligodendrocyte lineage cells for
      patch-clamp recording. Overall, these results show that CRISPR/Cas9 gene editing
      technology in germline-competent rat ESCs is enabling for in vitro studies and
      for generating genetically modified rats.

PMID- 29020617
TI  - Live Imaging Reveals that the First Division of Differentiating Human Embryonic
      Stem Cells Often Yields Asymmetric Fates.
AB  - How do stem cells respond to signals to initiate differentiation? Here, we show
      that, despite uniform exposure to differentiation-inducing extracellular signals,
      individual human embryonic stem cells (hESCs) respond heterogeneously. To track
      how hESCs incipiently exit pluripotency, we established a system to differentiate
      hESCs as single cells and conducted live imaging to track their very first cell
      division. We followed the fate of their earliest daughters as they remained
      undifferentiated or differentiated toward the primitive streak (the earliest
      descendants of pluripotent cells). About 30%-50% of the time, hESCs divided to
      yield one primitive streak and one undifferentiated daughter. The
      undifferentiated daughter cell was innately resistant to WNT signaling and could
      not respond to this primitive-streak-specifying differentiation signal. Hence,
      the first division of differentiating hESCs sometimes yields daughters with
      diverging fates, with implications for the efficiency of directed differentiation
      protocols and the underlying rules of lineage commitment.

PMID- 29020618
TI  - Hotspots of De Novo Point Mutations in Induced Pluripotent Stem Cells.
AB  - Induced pluripotent stem cells (iPSCs) are generated by direct reprogramming of
      somatic cells and hold great promise for novel therapies. However, several
      studies have reported genetic variations in iPSC genomes. Here, we investigated
      point mutations identified by whole-genome sequencing in mouse and human iPSCs in
      the context of epigenetic status. In contrast to disease-causing single
      nucleotide polymorphisms, de novo point mutations introduced during reprogramming
      were underrepresented in protein-coding genes and in open chromatin regions,
      including transcription factor binding sites. Instead, these mutations occurred
      preferentially in structurally condensed lamina-associated heterochromatic
      domains, suggesting that chromatin organization is a factor that can bias the
      regional mutation rate in iPSC genomes. Mutation signature analysis implicated
      oxidative stress associated with reprogramming as a likely cause of point
      mutations. Altogether, our study provides deeper understanding of the mutational
      landscape of iPSC genomes, paving an important way toward the translation of iPSC
      based cell therapy.

PMID- 29020619
TI  - Remarkable Stability of Myelinating Oligodendrocytes in Mice.
AB  - New myelin-forming oligodendrocytes (OLs) are generated in the mouse central
      nervous system during adulthood. These adult-born OLs might augment the existing
      population, contributing to neural plasticity, or else replace OLs that die in
      use (turnover). To distinguish between these alternatives, we induced genetic
      labeling of mature myelinating OLs in young adult mice and tracked their
      subsequent survival. OL survival rates were region dependent, being higher in
      corpus callosum (~90% survival over 20 months) and motor cortex (~70% survival)
      than in corticospinal tract or optic nerve (50%-60% survival). Survival rates
      over the first 8 months were 90%-100% in all regions except the optic nerve. In
      the corpus callosum, new OLs accumulate during young adulthood and are therefore
      likely to participate in adaptive myelination. We also found that the number of
      myelin internodes maintained by individual cortical OLs is stable for at least 8
      months but declines ~12% in the following year.

PMID- 29020621
TI  - Fanconi-Anemia-Associated Mutations Destabilize RAD51 Filaments and Impair
      Replication Fork Protection.
AB  - Fanconi anemia (FA) is a genetic disorder characterized by a defect in DNA
      interstrand crosslink (ICL) repair, chromosomal instability, and a predisposition
      to cancer. Recently, two RAD51 mutations were reported to cause an FA-like
      phenotype. Despite the tight association of FA/HR proteins with replication fork
      (RF) stabilization during normal replication, it remains unknown how FA
      associated RAD51 mutations affect replication beyond ICL lesions. Here, we report
      that these mutations fail to protect nascent DNA from MRE11-mediated degradation
      during RF stalling in Xenopus laevis egg extracts. Reconstitution of DNA
      protection in vitro revealed that the defect arises directly due to altered RAD51
      properties. Both mutations induce pronounced structural changes and RAD51
      filament destabilization that is not rescued by prevention of ATP hydrolysis due
      to aberrant ATP binding. Our results further interconnect the FA pathway with DNA
      replication and provide mechanistic insight into the role of RAD51 in
      recombination-independent mechanisms of genome maintenance.

PMID- 29020620
TI  - Enhancement of BLM-DNA2-Mediated Long-Range DNA End Resection by CtIP.
AB  - DNA double-strand break repair by homologous recombination entails the resection
      of DNA ends to reveal ssDNA tails, which are used to invade a homologous DNA
      template. CtIP and its yeast ortholog Sae2 regulate the nuclease activity of
      MRE11 in the initial stage of resection. Deletion of CtIP in the mouse or SAE2 in
      yeast engenders a more severe phenotype than MRE11 nuclease inactivation,
      indicative of a broader role of CtIP/Sae2. Here, we provide biochemical evidence
      that CtIP promotes long-range resection via the BLM-DNA2 pathway. Specifically,
      CtIP interacts with BLM and enhances its helicase activity, and it enhances DNA
      cleavage by DNA2. Thus, CtIP influences multiple aspects of end resection beyond
      MRE11 regulation.

PMID- 29020622
TI  - Homeostatic Presynaptic Plasticity Is Specifically Regulated by P/Q-type Ca2+
      Channels at Mammalian Hippocampal Synapses.
AB  - Voltage-dependent Ca2+ channels (VGCC) represent the principal source of Ca2+
      ions driving evoked neurotransmitter release at presynaptic boutons. In mammals,
      presynaptic Ca2+ influx is mediated mainly via P/Q-type and N-type VGCC, which
      differ in their properties. Changes in their relative contributions tune
      neurotransmission both during development and in Hebbian plasticity. However,
      whether this represents a functional motif also present in other forms of
      activity-dependent regulation is unknown. Here, we study the role of VGCC in
      homeostatic plasticity (HSP) in mammalian hippocampal neurons using optical
      techniques. We find that changes in evoked Ca2+ currents specifically through P/Q
      type, but not N-type, VGCC mediate bidirectional homeostatic regulation of both
      neurotransmitter release efficacy and the size of the major synaptic vesicle
      pools. Selective dependence of HSP on P/Q-type VGCC in mammalian terminals has
      important implications for phenotypes associated with P/Q-type channelopathies,
      including migraine and epilepsy.

PMID- 29020623
TI  - Functional Plasticity of Odor Representations during Motherhood.
AB  - Motherhood is accompanied by new behaviors aimed at ensuring the wellbeing of the
      offspring. Olfaction plays a key role in guiding maternal behaviors during this
      transition. We studied functional changes in the main olfactory bulb (OB) of
      mothers in mice. Using in vivo two-photon calcium imaging, we studied the sensory
      representation of odors by mitral cells (MCs). We show that MC responses to
      monomolecular odors become sparser and weaker in mothers. In contrast, responses
      to biologically relevant odors are spared from sparsening or strengthen. MC
      responses to mixtures and to a range of concentrations suggest that these
      differences between odor responses cannot be accounted for by mixture suppressive
      effects or gain control mechanisms. In vitro whole-cell recordings show an
      increase in inhibitory synaptic drive onto MCs. The increase of inhibitory tone
      may contribute to the general decrease in responsiveness and concomitant enhanced
      representation of specific odors.

PMID- 29020624
TI  - Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell
      Resolution.
AB  - Microglia, the tissue-resident macrophages in the brain, are damage sensors that
      react to nearly any perturbation, including neurodegenerative diseases such as
      Alzheimer's disease (AD). Here, using single-cell RNA sequencing, we determined
      the transcriptome of more than 1,600 individual microglia cells isolated from the
      hippocampus of a mouse model of severe neurodegeneration with AD-like phenotypes
      and of control mice at multiple time points during progression of
      neurodegeneration. In this neurodegeneration model, we discovered two molecularly
      distinct reactive microglia phenotypes that are typified by modules of co
      regulated type I and type II interferon response genes, respectively.
      Furthermore, our work identified previously unobserved heterogeneity in the
      response of microglia to neurodegeneration, discovered disease stage-specific
      microglia cell states, revealed the trajectory of cellular reprogramming of
      microglia in response to neurodegeneration, and uncovered the underlying
      transcriptional programs.

PMID- 29020625
TI  - Overproduction of Neurons Is Correlated with Enhanced Cortical Ensembles and
      Increased Perceptual Discrimination.
AB  - Brains vary greatly in neuronal number and density, even across individuals
      within the same species, yet it remains unclear whether such variation leads to
      differences in brain function or behavior. By imaging cortical activity of a
      mouse model in which neuronal production is moderately enhanced in utero, we find
      that animals with more cortical neurons also develop enhanced functional
      correlations and more distinct neuronal ensembles in primary visual cortex. These
      mice also have sharper orientation discrimination in their visual behavior. These
      results unveil a correlation between neuronal ensembles and behavior and suggest
      that neuronal number is linked to functional modularity and perceptual
      discrimination of visual cortex. By experimentally linking differences in
      neuronal number and behavior, our findings could help explain how evolutionary
      and developmental variability of individual and species brain size may lead to
      perceptual and cognitive differences.

PMID- 29020626
TI  - Uncoupling of Metabolic Health from Longevity through Genetic Alteration of
      Adipose Tissue Lipid-Binding Proteins.
AB  - Deterioration of metabolic health is a hallmark of aging and generally assumed to
      be detrimental to longevity. Exposure to a high-calorie diet impairs metabolism
      and accelerates aging; conversely, calorie restriction (CR) prevents age-related
      metabolic diseases and extends lifespan. However, it is unclear whether
      preservation of metabolic health is sufficient to extend lifespan. We utilized a
      genetic mouse model lacking Fabp4/5 that confers protection against metabolic
      diseases and shares molecular and lipidomic features with CR to address this
      question. Fabp-deficient mice exhibit extended metabolic healthspan, with
      protection against insulin resistance and glucose intolerance, inflammation,
      deterioration of adipose tissue integrity, and fatty liver disease. Surprisingly,
      however, Fabp-deficient mice did not exhibit any extension of lifespan. These
      data indicate that extension of metabolic healthspan in the absence of CR can be
      uncoupled from lifespan, indicating the potential for independent drivers of
      these pathways, at least in laboratory mice.

PMID- 29020627
TI  - A Specific ChREBP and PPARalpha Cross-Talk Is Required for the Glucose-Mediated
      FGF21 Response.
AB  - While the physiological benefits of the fibroblast growth factor 21 (FGF21)
      hepatokine are documented in response to fasting, little information is available
      on Fgf21 regulation in a glucose-overload context. We report that peroxisome
      proliferator-activated receptor alpha (PPARalpha), a nuclear receptor of the
      fasting response, is required with the carbohydrate-sensitive transcription
      factor carbohydrate-responsive element-binding protein (ChREBP) to balance FGF21
      glucose response. Microarray analysis indicated that only a few hepatic genes
      respond to fasting and glucose similarly to Fgf21. Glucose-challenged Chrebp-/-
      mice exhibit a marked reduction in FGF21 production, a decrease that was rescued
      by re-expression of an active ChREBP isoform in the liver of Chrebp-/- mice.
      Unexpectedly, carbohydrate challenge of hepatic Pparalpha knockout mice also
      demonstrated a PPARalpha-dependent glucose response for Fgf21 that was associated
      with an increased sucrose preference. This blunted response was due to decreased
      Fgf21 promoter accessibility and diminished ChREBP binding onto Fgf21
      carbohydrate-responsive element (ChoRE) in hepatocytes lacking PPARalpha. Our
      study reports that PPARalpha is required for the ChREBP-induced glucose response
      of FGF21.

PMID- 29020628
TI  - Molecular Mechanism by which Prominent Human Gut Bacteroidetes Utilize Mixed
      Linkage Beta-Glucans, Major Health-Promoting Cereal Polysaccharides.
AB  - Microbial utilization of complex polysaccharides is a major driving force in
      shaping the composition of the human gut microbiota. There is a growing
      appreciation that finely tuned polysaccharide utilization loci enable ubiquitous
      gut Bacteroidetes to thrive on the plethora of complex polysaccharides that
      constitute "dietary fiber." Mixed-linkage beta(1,3)/beta(1,4)-glucans (MLGs) are
      a key family of plant cell wall polysaccharides with recognized health benefits
      but whose mechanism of utilization has remained unclear. Here, we provide
      molecular insight into the function of an archetypal MLG utilization locus
      (MLGUL) through a combination of biochemistry, enzymology, structural biology,
      and microbiology. Comparative genomics coupled with growth studies demonstrated
      further that syntenic MLGULs serve as genetic markers for MLG catabolism across
      commensal gut bacteria. In turn, we surveyed human gut metagenomes to reveal that
      MLGULs are ubiquitous in human populations globally, which underscores the
      importance of gut microbial metabolism of MLG as a common cereal polysaccharide.

PMID- 29020629
TI  - Differential Regulation of Lipoprotein and Hepatitis C Virus Secretion by Rab1b.
AB  - Secretory cells produce diverse cargoes, yet how they regulate concomitant
      secretory traffic remains insufficiently explored. Rab GTPases control
      intracellular vesicular transport. To map secretion pathways, we generated a
      library of lentivirus-expressed dominant-negative Rab mutants and used it in a
      large-scale screen to identify regulators of hepatic lipoprotein secretion. We
      identified several candidate pathways, including those mediated by Rab11 and
      Rab8. Surprisingly, inhibition of Rab1b, the major regulator of transport from
      the endoplasmic reticulum to the Golgi, differently affected the secretion of the
      very-low-density lipoprotein components ApoE and ApoB100, despite their final
      association on mature secreted lipoprotein particles. Since hepatitis C virus
      (HCV) incorporates ApoE and ApoB100 into its virus particle, we also investigated
      infectious HCV secretion and show that its regulation by Rab1b mirrors that of
      ApoB100. These observations reveal differential regulation of hepatocyte
      secretion by Rab1b and advance our understanding of lipoprotein assembly and
      lipoprotein and HCV secretion.

PMID- 29020633
TI  - Erasure of Tet-Oxidized 5-Methylcytosine by a SRAP Nuclease.
AB  - Enzymatic oxidation of 5-methylcytosine (5mC) in DNA by the Tet dioxygenases
      reprograms genome function in embryogenesis and postnatal development. Tet
      oxidized derivatives of 5mC such as 5-hydroxymethylcytosine (5hmC) act as
      transient intermediates in DNA demethylation or persist as durable marks, yet how
      these alternative fates are specified at individual CpGs is not understood. Here,
      we report that the SOS response-associated peptidase (SRAP) domain protein Srap1,
      the mammalian ortholog of an ancient protein superfamily associated with DNA
      damage response operons in bacteria, binds to Tet-oxidized forms of 5mC in DNA
      and catalyzes turnover of these bases to unmodified cytosine by an autopeptidase
      coupled nuclease. Biallelic inactivation of murine Srap1 causes embryonic
      sublethality associated with widespread accumulation of ectopic 5hmC. These
      findings establish a function for a class of DNA base modification-selective
      nucleases and position Srap1 as a determinant of 5mC demethylation trajectories
      during mammalian embryonic development.

PMID- 29020630
TI  - Degradation of Bcl-2 by XIAP and ARTS Promotes Apoptosis.
AB  - We describe a mechanism by which the anti-apoptotic B cell lymphoma 2 (Bcl-2)
      protein is downregulated to induce apoptosis. ARTS (Sept4_i2) is a tumor
      suppressor protein that promotes cell death through specifically antagonizing
      XIAP (X-linked inhibitor of apoptosis). ARTS and Bcl-2 reside at the outer
      mitochondrial membrane in living cells. Upon apoptotic induction, ARTS brings
      XIAP and Bcl-2 into a ternary complex, allowing XIAP to promote ubiquitylation
      and degradation of Bcl-2. ARTS binding to Bcl-2 involves the BH3 domain of Bcl-2.
      Lysine 17 in Bcl-2 serves as the main acceptor for ubiquitylation, and a Bcl-2
      K17A mutant has increased stability and is more potent in protection against
      apoptosis. Bcl-2 ubiquitylation is reduced in both XIAP- and Sept4/ARTS-deficient
      MEFs, demonstrating that XIAP serves as an E3 ligase for Bcl-2 and that ARTS is
      essential for this process. Collectively, these results suggest a distinct model
      for the regulation of Bcl-2 by ARTS-mediated degradation.

PMID- 29020631
TI  - Covalent Modifications of Histone H3K9 Promote Binding of CHD3.
AB  - Chromatin remodeling is required for genome function and is facilitated by ATP
      dependent complexes, such as nucleosome remodeling and deacetylase (NuRD). Among
      its core components is the chromodomain helicase DNA binding protein 3 (CHD3)
      whose functional significance is not well established. Here, we show that CHD3 co
      localizes with the other NuRD subunits, including HDAC1, near the H3K9ac-enriched
      promoters of the NuRD target genes. The tandem PHD fingers of CHD3 bind histone
      H3 tails and posttranslational modifications that increase hydrophobicity of H3K9
      methylation or acetylation (H3K9me3 or H3K9ac)-enhance this interaction. Binding
      of CHD3 PHDs promotes H3K9Cme3-nucleosome unwrapping in vitro and perturbs the
      pericentric heterochromatin structure in vivo. Methylation or acetylation of H3K9
      uniquely alleviates the intra-nucleosomal interaction of histone H3 tails,
      increasing H3K9 accessibility. Collectively, our data suggest that the targeting
      of covalently modified H3K9 by CHD3 might be essential in diverse functions of
      NuRD.

PMID- 29020632
TI  - Activation of the p53 Transcriptional Program Sensitizes Cancer Cells to Cdk7
      Inhibitors.
AB  - Cdk7, the CDK-activating kinase and transcription factor IIH component, is a
      target of inhibitors that kill cancer cells by exploiting tumor-specific
      transcriptional dependencies. However, whereas selective inhibition of analog
      sensitive (AS) Cdk7 in colon cancer-derived cells arrests division and disrupts
      transcription, it does not by itself trigger apoptosis efficiently. Here, we show
      that p53 activation by 5-fluorouracil or nutlin-3 synergizes with a reversible
      Cdk7as inhibitor to induce cell death. Synthetic lethality was recapitulated with
      covalent inhibitors of wild-type Cdk7, THZ1, or the more selective YKL-1-116. The
      effects were allele specific; a CDK7as mutation conferred both sensitivity to
      bulky adenine analogs and resistance to covalent inhibitors. Non-transformed
      colon epithelial cells were resistant to these combinations, as were cancer
      derived cells with p53-inactivating mutations. Apoptosis was dependent on death
      receptor DR5, a p53 transcriptional target whose expression was refractory to
      Cdk7 inhibition. Therefore, p53 activation induces transcriptional dependency to
      sensitize cancer cells to Cdk7 inhibition.

PMID- 29020635
TI  - Human Organ Chip Models Recapitulate Orthotopic Lung Cancer Growth, Therapeutic
      Responses, and Tumor Dormancy In Vitro.
AB  - Here, we show that microfluidic organ-on-a-chip (organ chip) cell culture
      technology can be used to create in vitro human orthotopic models of non-small
      cell lung cancer (NSCLC) that recapitulate organ microenvironment-specific cancer
      growth, tumor dormancy, and responses to tyrosine kinase inhibitor (TKI) therapy
      observed in human patients in vivo. Use of the mechanical actuation
      functionalities of this technology revealed a previously unknown sensitivity of
      lung cancer cell growth, invasion, and TKI therapeutic responses to physical cues
      associated with breathing motions, which appear to be mediated by changes in
      signaling through epidermal growth factor receptor (EGFR) and MET protein kinase.
      These findings might help to explain the high level of resistance to therapy in
      cancer patients with minimal residual disease in regions of the lung that remain
      functionally aerated and mobile, in addition to providing an experimental model
      to study cancer persister cells and mechanisms of tumor dormancy in vitro.

PMID- 29020634
TI  - Brachyury-YAP Regulatory Axis Drives Stemness and Growth in Cancer.
AB  - Molecular factors that define stem cell identity have recently emerged as
      oncogenic drivers. For instance, brachyury, a key developmental transcriptional
      factor, is also implicated in carcinogenesis, most notably of chordoma, through
      mechanisms that remain elusive. Here, we show that brachyury is a crucial
      regulator of stemness in chordoma and in more common aggressive cancers.
      Furthermore, this effect of brachyury is mediated by control of synthesis and
      stability of Yes-associated protein (YAP), a key regulator of tissue growth and
      homeostasis, providing an unexpected mechanism of control of YAP expression. We
      further demonstrate that the brachyury-YAP regulatory pathway is associated with
      tumor aggressiveness. These results elucidate a mechanism of controlling both
      tumor stemness and aggressiveness through regulatory coupling of two
      developmental factors.

PMID- 29020638
TI  - Proteomics Reveals Global Regulation of Protein SUMOylation by ATM and ATR
      Kinases during Replication Stress.
AB  - The mechanisms that protect eukaryotic DNA during the cumbersome task of
      replication depend on the precise coordination of several post-translational
      modification (PTM)-based signaling networks. Phosphorylation is a well-known
      regulator of the replication stress response, and recently an essential role for
      SUMOs (small ubiquitin-like modifiers) has also been established. Here, we
      investigate the global interplay between phosphorylation and SUMOylation in
      response to replication stress. Using SUMO and phosphoproteomic technologies, we
      identify thousands of regulated modification sites. We find co-regulation of
      central DNA damage and replication stress responders, of which the ATR-activating
      factor TOPBP1 is the most highly regulated. Using pharmacological inhibition of
      the DNA damage response kinases ATR and ATM, we find that these factors regulate
      global protein SUMOylation in the protein networks that protect DNA upon
      replication stress and fork breakage, pointing to integration between
      phosphorylation and SUMOylation in the cellular systems that protect DNA
      integrity.

PMID- 29020637
TI  - Combinatorial Microenvironments Impose a Continuum of Cellular Responses to a
      Single Pathway-Targeted Anti-cancer Compound.
AB  - Tumor microenvironments are a driver of resistance to anti-cancer drugs.
      Dissecting cell-microenvironment interactions into tractable units of study
      presents a challenge. Here, we assess the impact of hundreds of tumor-inspired
      microenvironments, in parallel, on lapatinib responses in four cancer cell lines.
      Combinations of ECM and soluble factors were printed on stiffness-tunable
      substrata to generate a collection of controlled microenvironments in which to
      explore cell-based functional responses. Proliferation, HER2 protein expression
      and phosphorylation, and morphology were measured in single cells. Using
      dimension reduction and linear modeling, the effects of microenvironment
      constituents were identified and then validated empirically. Each of the cell
      lines exhibits unique microenvironment-response patterns. Fibronectin, type IV
      collagen, and matrix rigidity are significant regulators of lapatinib resistance
      in HER2-amplified breast cancer cells. Small-molecule inhibitors were identified
      that could attenuate microenvironment-imposed resistance. Thus, we demonstrate a
      strategy to identify resistance- and sensitivity-driving microenvironments to
      improve the efficacy of anti-cancer therapeutics.

PMID- 29020636
TI  - Self-Organized Cerebral Organoids with Human-Specific Features Predict Effective
      Drugs to Combat Zika Virus Infection.
AB  - The human cerebral cortex possesses distinct structural and functional features
      that are not found in the lower species traditionally used to model brain
      development and disease. Accordingly, considerable attention has been placed on
      the development of methods to direct pluripotent stem cells to form human brain
      like structures termed organoids. However, many organoid differentiation
      protocols are inefficient and display marked variability in their ability to
      recapitulate the three-dimensional architecture and course of neurogenesis in the
      developing human brain. Here, we describe optimized organoid culture methods that
      efficiently and reliably produce cortical and basal ganglia structures similar to
      those in the human fetal brain in vivo. Neurons within the organoids are
      functional and exhibit network-like activities. We further demonstrate the
      utility of this organoid system for modeling the teratogenic effects of Zika
      virus on the developing brain and identifying more susceptibility receptors and
      therapeutic compounds that can mitigate its destructive actions.

PMID- 29020639
TI  - Associations between immunological function and memory recall in healthy adults.
AB  - Studies in clinical and aging populations support associations between
      immunological function, cognition and mood, although these are not always in line
      with animal models. Moreover, very little is known about the relationship between
      immunological measures and cognition in healthy young adults. The present study
      tested associations between the state of immune system and memory recall in a
      group of relatively healthy adults. Immediate and delayed memory recall was
      assessed in 30 participants using the computerised cognitive battery. CD4, CD8
      and CD69 subpopulations of lymphocytes, Interleukin-6 (IL-6) and cortisol were
      assessed with blood assays. Correlation analysis showed significant negative
      relationships between CD4 and the short and long delay memory measures. IL-6
      showed a significant positive correlation with long-delay recall. Generalized
      linear models found associations between differences in all recall challenges and
      CD4. A multivariate generalized linear model including CD4 and IL-6 exhibited a
      stronger association. Results highlight the interactions between CD4 and IL-6 in
      relation to memory function. Further study is necessary to determine the
      underlying mechanisms of the associations between the state of immune system and
      cognitive performance.

PMID- 29020640
TI  - Bridging spatially segregated redox zones with a microbial electrochemical
      snorkel triggers biogeochemical cycles in oil-contaminated River Tyne (UK)
      sediments.
AB  - Marine sediments represent an important sink for a number of anthropogenic
      organic contaminants, including petroleum hydrocarbons following an accidental
      oil spill. Degradation of these compounds largely depends on the activity of
      sedimentary microbial communities linked to biogeochemical cycles, in which
      abundant elements such as iron and sulfur are shuttled between their oxidized and
      reduced forms. Here we show that introduction of a small electrically conductive
      graphite rod ("the electrochemical snorkel") into an oil-contaminated River Tyne
      (UK) sediment, so as to create an electrochemical connection between the anoxic
      contaminated sediment and the oxygenated overlying water, has a large impact on
      the rate of metabolic reactions taking place in the bulk sediment. The
      electrochemical snorkel accelerated sulfate reduction processes driven by organic
      contaminant oxidation and suppressed competitive methane-producing reactions. The
      application of a comprehensive suite of chemical, spectroscopic, biomolecular and
      thermodynamic analyses suggested that the snorkel served as a scavenger of toxic
      sulfide via a redox interaction with the iron cycle. Taken as a whole, the
      results of this work highlight a new strategy for controlling biological
      processes, such as bioremediation, through the manipulation of the electron flows
      in contaminated sediments.

PMID- 29020641
TI  - Assessing membrane biofouling and its gel layer of anoxic/oxic membrane
      bioreactor for megacity municipal wastewater treatment during plum rain season in
      Yangtze River Delta, China.
AB  - This study assessed membrane biofouling and its gel layer of anoxic/oxic membrane
      bioreactor (A/O-MBR) for megacity municipal wastewater treatment during plum rain
      season, which was continuous rainy weather, in Yangtze River Delta, China. A
      laboratory-scale A/O-MBR was operated to treat the municipal wastewater from
      Quyang wastewater treatment plant, which located at the typical megacity of
      Shanghai in Yangtze River Delta, from April to July accompanying with plum rain
      season. As reactor performance showed, CODCr, NH4+-N, TN, TP of the influent
      gradually decreased during plum rain season, and inhibited pollutant removal due
      to organic carbon shortage. However, dissolve inorganic carbon and inorganic
      components in mixed liquid had an obvious increase under rainy weather. Membrane
      filtration results indicated that plum rain season enhanced pore blocking
      behavior, further leading to the serious membrane biofouling but inhibiting gel
      layer formation. Additionally, gel layer analysis predicted that plum rain season
      led to plenty of inorganic components and precipitate flew into A/O-MBR reactor.
      Inorganic components with elements of Ca, Mg Ba, Fe, Al and Si seriously blocked
      membrane pores. Those components also accumulated into gel layer in the form of
      SiO2, CaCO3, CaSiO3, MgNH4PO4, BaCO3, AlPO4, etc. Consequently, plum rain season
      enhanced pore blocking behavior and led to severe membrane biofouling but with
      the inhibition of gel layer formation.

PMID- 29020642
TI  - cBiT: A transcriptomics database for innovative biomaterial engineering.
AB  - Creating biomaterials that are suited for clinical application is still hampered
      by a lack of understanding of the interaction between a cell and the biomaterial
      surface it grows on. This surface communication can strongly impact cellular
      behavior, which in turn affects the chances of a successful interaction between a
      material and the host tissue. Transcriptomics data have previously been linked to
      measurements of biomaterial properties in order to explain the biological
      mechanisms underlying these cell-biomaterial interactions. However, such multi
      assay data are highly complex and therefore require careful and unambiguous
      characterization and storage. Failure to do so may result in loss of valuable
      data or erroneous data analysis. In order to start a new initiative that tackles
      these issues and offers a platform for innovative biomaterial development, we
      have created a publically accessible repository called The Compendium for
      Biomaterial Transcriptomics (cBiT, https://cbit.maastrichtuniversity.nl). cBiT is
      a data warehouse that gives users the opportunity to search through biomaterial
      based transcriptomics data sets using a web interface. Data of interest can be
      selected and downloaded, together with associated measurements of material
      properties. Researchers are also invited to add their data to cBiT in order to
      further enhance its scientific value. We aim to make cBiT the hub for biomaterial
      associated data, thereby enabling major contributions to a more efficient
      development of new materials with improved body integration. Here, we describe
      the structure of cBiT and provide a use case with clinically applied materials to
      demonstrate how cBiT can be used to correlate data across transcriptomics
      studies.

PMID- 29020643
TI  - Association of methylmercury intake from seafood consumption and blood mercury
      level among the Asian and Non-Asian populations in the United States.
AB  - BACKGROUND: MeHg is a well-established neurotoxicant for fetal brain growth and
      development and has been shown to increase the risk of cardiovascular disease in
      aging populations. In the U.S., Asian populations are of particular concern
      because of their seafood consumption behaviors. OBJECTIVES: Our objective was to
      calculate the average daily MeHg intake (ADMI) from seafood and to assess the
      relationship between ADMI with blood methylmercury (BMeHg) concentrations,
      specifically among women of reproductive age (WORA) and adults >= 50 years of
      age. METHODS: We estimated ADMI from seafood using the 30-day fish consumption
      data from the NHANES 2011-2014 datasets. Using multivariable linear regression,
      we estimated the proportional change in mean BMeHg associated with a doubling of
      the ADMI. Further, correlations between ADMI and BMeHg were compared between
      Asians and other racial/ethnic groups. RESULTS: Our analysis found both Asian
      WORA and Asian adults age >= 50 years old had significantly higher BMeHg levels
      and ADMI than their Non-Asian counterparts. Correlations between ADMI from
      seafood and blood Hg levels were stronger among Asian WORA than among Non-Asian
      WORA. Key fish species that influenced the dietary MeHg intake for Asians were
      mackerel, tuna, and "other known/unknown fish species". CONCLUSION: We confirmed
      that Asian populations have higher MeHg intake than the Non-Asian population in
      the U.S. and seafood intake is a key predictor of blood Hg concentration,
      especially among Asian women of reproductive age. Future studies should
      incorporate information on other known and unknown fish species that are
      frequently consumed by Asian populations and different parts and fish organs
      eaten to better understand determinants of MeHg exposure.

PMID- 29020644
TI  - Di(2-ethylhexyl) phthalate and diethyl phthalate disrupt lipid metabolism, reduce
      fecundity and shortens lifespan of Caenorhabditis elegans.
AB  - The widespread use of phthalates is of major concern as they have adverse effects
      on many different physiological functions, including reproduction, metabolism and
      cell differentiation. The aim of this study was to compare the toxicity of the
      widely-used di (2-ethydlhexyl) phthalate (DEHP) with its substitute, diethyl
      phthalate (DEP). We analyzed the toxicity of these two phthalates using
      Caenorhabditis elegans as a model system. Gene expression analysis following
      exposure during the L1 to young adult stage showed that DEHP and DEP alter the
      expression of genes involved in lipid metabolism and stress response. Genes
      associated with lipid metabolism, including fasn-1, pod-2, fat-5, acs-6 and sbp
      1, and vitellogenin were upregulated. Among the stress response genes, ced-1 wah
      1, daf-21 and gst-4 were upregulated, while ctl-1, cdf-2 and the heat shock
      proteins (hsp-16.1, hsp-16.48 and sip-1) were downregulated. Lipid staining
      revealed that DEHP significantly increased lipid content following 1 MUM
      exposure, however, DEP required 10 MUM exposure to elicit an effect. Both DEHP
      and DEP reduced the fecundity at 1 MUM concentration. Lifespan analysis indicated
      that DEHP and DEP reduced the average lifespan from 14 days in unexposed worms to
      13 and 12 days, respectively. Expression of lifespan associated genes showed a
      correlation to shortened lifespan in the exposed groups. As reported previously,
      our data also indicates that the banned DEHP is toxic to C. elegans, however its
      substitute DEP has not been previously tested in this model organism and our data
      revealed that DEP is equally potent as DEHP in regulating C. elegans
      physiological functions.

PMID- 29020645
TI  - Neural correlates of the lexicality effect in children.
AB  - The comparison of words and pseudowords has been extensively used in adult
      neuroimaging studies to inform neurocognitive models of reading but has rarely
      been used to inform models of reading acquisition. Using a rhyming judgment task,
      the current study examined age-related differences in the spelling to sound
      mapping mechanisms involved in word and pseudoword reading. We hypothesized a
      developmental increase in specialization of the brain mechanisms engaged for word
      and pseudoword processing. Consistent with adult studies, children in the current
      study demonstrated a greater activation for words as compared to pseudowords in
      the anterior left ventral occipito-temporal cortex (vOT). Inconsistent with adult
      studies, children also showed greater activation for words as compared to
      pseudowords in the mid-posterior left vOT, indicating a robust semantic influence
      on orthographic processing in young readers. Furthermore, our results did not
      indicate a lexicality by age interaction for 8- to 13-year-old children,
      suggesting that the adult-like specialization in the left vOT only appears later
      in development.

PMID- 29020647
TI  - Body image and paranoia.
AB  - Paranoia builds upon feelings of vulnerability. Our clinical experience indicates
      that negative body image, including concerns regarding weight, may be one source
      of feeling vulnerable and hence raise the risk of paranoia. There has been no
      empirical test of an association between body image and paranoia. Our aim was to
      provide the first test of this issue by examining in epidemiologically
      representative cohorts the cross-sectional associations between paranoia and a
      proxy measure of body image. This was an initial exploration of a potentially
      important but overlooked issue. Data were used from 5515 participants in the US
      National Comorbidity Survey-Replication (NCS-R). To validate the findings, the
      analyses were replicated with 10,113 participants in the US National Comorbidity
      Survey-Adolescents (NCS-A). Concerns about weight were associated with paranoia
      in the NCS-R (OR = 1.48, p = 0.006, CI = 1.123, 1.955) and NCS-A (OR = 1.67, p <
      0.001, CI = 1.490, 1.873). The associations remained significant after
      controlling for gender and body mass index. The results show that negative body
      image and paranoia are associated in the general population, consistent with the
      idea that paranoia may build upon feelings of vulnerability arising from body
      image concerns. Studies are needed to examine whether there is a causal
      relationship.

PMID- 29020648
TI  - Ambient black carbon particulate matter in the coal region of Dhanbad, India.
AB  - Light-absorbing, atmospheric particles have gained greater attention in recent
      years because of their direct and indirect impacts on regional and global
      climate. Atmospheric black carbon (BC) aerosol is a leading climate warming
      agent, yet uncertainties in the global direct aerosol radiative forcing remain
      large. Based on a year of aerosol absorption measurements at seven wavelengths,
      BC concentrations were investigated in Dhanbad, the coal capital of India. Coal
      is routinely burned for cooking and residential heat as well as in small
      industries. The mean daily concentrations of ultraviolet-absorbing black carbon
      measured at 370nm (UVBC) and black carbon measured at 880nm (BC) were 9.8+/-5.7
      and 6.5+/-3.8MUgm-3, respectively. The difference between UVBC and BC, Delta-C,
      is an indicator of biomass or residential coal burning and averaged 3.29+/
      4.61MUgm-3. An alternative approach uses the Angstrom Exponent (AE) to estimate
      the biomass/coal and traffic BC concentrations. Biomass/coal burning contributed
      ~87% and high temperature, fossil-fuel combustion contributed ~13% to the annual
      average BC concentration. The post-monsoon seasonal mean UVBC values were
      10.9MUgm-3 and BC of 7.2MUgm-3. Potential source contribution function analysis
      showed that in the post-monsoon season, air masses came from the central and
      northwestern Indo-Gangetic Plains where there is extensive agricultural burning.
      The mean winter UVBC and BC concentrations were 15.0 and 10.1MUgm-3,
      respectively. These higher values were largely produced by local sources under
      poor dispersion conditions. The direct radiative forcing (DRF) due to UVBC and BC
      at the surface (SUR) and the top of the atmosphere (TOA) were calculated. The
      mean atmospheric heating rates due to UVBC and BC were estimated to be 1.40
      degrees Kday-1 and 1.18 degrees Kday-1, respectively. This high heating rate may
      affect the monsoon circulation in this region.

PMID- 29020650
TI  - Decision making under risk and under ambiguity in depressed suicide attempters,
      depressed non-attempters and healthy controls.
AB  - BACKGROUND: A number of neuropsychological alterations have been found in
      patients who have attempted suicide. Most studies investigating decision making
      (DM) abilities in suicide attempters so far have used one single DM task and
      included patients with a lifetime history of suicide attempts. These studies have
      yielded conflicting results. METHOD: In this study, currently depressed in
      patients who had a recent suicide attempt (within the last six months) (n = 21),
      depressed in-patients without a lifetime history of suicide attempts (n = 31) and
      a healthy control group (n = 26) were assessed with two tasks for the assessment
      of DM. The Game of Dice Task (GDT) measures DM under risk and the Iowa Gambling
      Task (IGT) DM under ambiguity. Further, depression severity, impulsiveness and
      suicidal intent of the current suicide attempt were assessed. RESULTS: Both
      depressed groups differed from controls with respect to marital and partnership
      status, smoking, impulsiveness and psychiatric family history. In terms of DM,
      IGT scores did not differ significantly between groups. However, suicide
      attempters made significantly more risky decisions as assessed with the GDT than
      both control groups (p < 0.05 for pairwise comparisons, p = 0.065 for overall
      comparison of the 3 groups). LIMITATIONS: The available tasks assess DM under
      laboratory conditions which may not reflect the emotional status of suicidal
      individuals. No general cognitive assessment was included. CONCLUSIONS: Depressed
      suicide attempters differed with regard to DM under risk but not DM under
      ambiguity. When studying DM it appears crucial to take varying aspects of DM into
      account.

PMID- 29020649
TI  - Neuroendocrine stress reactivity of male C57BL/6N mice following chronic oral
      corticosterone exposure during adulthood or adolescence.
AB  - Adolescence is associated with the maturation of the hypothalamic-pituitary
      adrenal (HPA) axis, the major neuroendocrine axis mediating the hormonal stress
      response. Adolescence is also a period in development marked by a variety of
      stress-related vulnerabilities, including psychological and physiological
      dysfunctions. Many of these vulnerabilities are accompanied by a disrupted HPA
      axis. In adult mice, a model of disrupted HPA function has been developed using
      oral chronic corticosterone administration via the drinking water, which results
      in various physiological and neurobehavioral abnormalities, including changes in
      stress reactivity and anxiety-like behaviors. In an effort to further complement
      and extend this model, we tested the impact of HPA disruption in adolescent mice.
      We also examined whether this disruption led to different outcomes depending on
      whether the treatment happened during adolescence or adulthood. In the current
      set of experiments, we exposed adult (70days of age) or adolescent (30days of
      age) male C57BL/6N mice to 4 weeks of either 0 or 25MUg/ml oral corticosterone
      via their drinking water. We measured body weight during treatment and plasma
      corticosterone levels and activation of the paraventricular nucleus (PVN), as
      indexed by FOS immunohistochemistry, before and after a 30min session of
      restraint stress. Our data indicate that adolescent animals exposed to chronic
      corticosterone showed weight loss during treatment, an effect not observed in
      adults. Further, we found stress failed to elevate plasma corticosterone levels
      in treated mice, regardless of whether exposure occurred in adulthood or
      adolescence. Despite this reduced hormonal responsiveness, we found significant
      neural activation in the PVN of both adult- and adolescent-treated mice,
      indicating a dissociation between stress-induced peripheral and central stress
      responses following chronic corticosterone exposure. Moreover, stress-induced
      neural activation in the PVN was unaffected by chronic corticosterone treatment
      in adult animals, but led to a hyper-responsive PVN in the corticosterone-treated
      adolescent animals, suggesting an age-specific effect of corticosterone treatment
      on later PVN stress reactivity. Together, these experiments highlight the
      influence of developmental stage on somatic and neuroendocrine outcomes following
      chronic HPA disruption by noninvasive, oral corticosterone treatment. Given the
      substantial vulnerabilities to HPA dysfunctions during adolescence this model may
      prove useful in better understanding these vulnerabilities.

PMID- 29020646
TI  - HIV-1 subtype CRF01_AE and B differ in utilization of low levels of CCR5,
      Maraviroc susceptibility and potential N-glycosylation sites.
AB  - HIV subtypes not only predominate in different geographical regions but also
      differ in key phenotypic characteristics. To determine if genotypic and/or
      phenotypic differences in the Envelope (Env) glycoprotein can explain subtype
      related differences, we cloned 37 full length Envs from Subtype B and AE HIV
      infected individuals from Singapore. Our data demonstrates that CRF01_AE Envs
      have lower Potential N Glycosylation Sites and higher risk of *4 development.
      Phenotypically, CRF01_AE were less infectious than subtype B Envs in cells
      expressing low levels of CCR5. Moreover, the Maraviroc IC50 was higher for
      subtype B Envs and correlated with infectivity in low CCR5 expressing cells as
      well as PNGS. Specifically, the glycosylation site N301 in the V3 loop was seen
      less frequently in AE subtype and CXCR4 topic viruses. CRF01_AE differs from B
      subtype in terms of CCR5 usage and Maraviroc susceptibility which may have
      implications for HIV pathogenesis and virus evolution.

PMID- 29020651
TI  - Is negative self-referent bias an endophenotype for depression? An fMRI study of
      emotional self-referent words in twins at high vs. low risk of depression.
AB  - BACKGROUND: Negative cognitive bias and aberrant neural processing of self
      referent emotional words seem to be trait-marks of depression. However, it is
      unclear whether these neurocognitive changes are present in unaffected first
      degree relatives and constitute an illness endophenotype. METHODS: Fifty-three
      healthy, never-depressed monozygotic or dizygotic twins with a co-twin history of
      depression (high-risk group: n = 26) or no first-degree family history of
      depression (low-risk group: n = 27) underwent neurocognitive testing and
      functional magnetic imaging (fMRI) as part of a follow-up cohort study.
      Participants performed a self-referent emotional word categorisation task and
      free word recall task followed by a recognition task during fMRI. Participants
      also completed questionnaires assessing mood, personality traits and coping
      strategies. RESULTS: High-risk and low-risk twins (age, mean +/- SD: 40 +/- 11)
      were well-balanced for demographic variables, mood, coping and neuroticism. High
      risk twins showed lower accuracy during self-referent categorisation of emotional
      words independent of valence and more false recollections of negative words than
      low-risk twins during free recall. Functional MRI yielded no differences between
      high-risk and low-risk twins in retrieval-specific neural activity for positive
      or negative words or during the recognition of negative versus positive words
      within the hippocampus or prefrontal cortex. CONCLUSIONS: The subtle display of
      negative recall bias is consistent with the hypothesis that self-referent
      negative memory bias is an endophenotype for depression. High-risk twins' lower
      categorisation accuracy adds to the evidence for valence-independent cognitive
      deficits in individuals at familial risk for depression.

PMID- 29020652
TI  - Negatively charged food additive dye "Allura Red" rapidly induces SDS-soluble
      amyloid fibril in beta-lactoglobulin protein.
AB  - Recent studies have led to an increased interest to categorize small molecular
      inhibitors of protein fibrillation. In this study, we used spectroscopy,
      microscopy and gel electrophoresis techniques that provides an elaborated
      description of the Allura Red-induced amyloid fibrillation in the beta-LG protein
      at two pHs (7.4 and 3.5). The spectroscopy results show that beta-LG protein form
      aggregates in the presence of Allura Red (0.04-15.0mM) at pH 3.5 due to
      electrostatic and hydrophobic interactions. However, at pH 7.4, the beta-LG does
      not interact electrostatically with Allura Red and therefore no aggregation
      occurred. The Allura Red-induced aggregates have an amyloid-like structure that
      was confirmed by far-UV CD, Congo Red and transmission electron microscopy (TEM).
      The CD spectrum of beta-LG contains single minima at ~218nm, which shifts towards
      higher wavelength minima at ~225nm in the presence of Allura Red, characteristics
      of the cross beta-sheet structure. The TEM results suggest that beta-LG form long
      straight fibril when exposed to Allura Red at pH 3.5. The Allura Red-induced
      amyloid fibril is SDS-soluble confirmed by SDS-PAGE techniques. A far UV CD
      result shows the conversion of Allura Red induced cross beta-sheet structure into
      alpha-helical structure in the presence of increasing concentration of SDS. The
      results of this study suggest that the electrostatic, as well as hydrophobic
      interactions play an important role during Allura Red-induced beta-LG
      fibrillation.

PMID- 29020653
TI  - Preparation of cashew gum-based flocculants by microwave- and ultrasound-assisted
      methods.
AB  - In this work, copolymers based on cashew gum (CG) grafted with polyacrylamide
      (PAM) were synthesized by microwave- and ultrasound-assisted methods, using
      potassium persulfate as an initiator in aqueous medium. The graft copolymers were
      characterized by Fourier-transform infrared spectroscopy, nuclear magnetic
      resonance spectroscopy, and thermogravimetric analysis. The efficiency of the
      graft copolymers (CG-g-PAM) in flocculation of a kaolin suspension was studied.
      Results indicated that the graft copolymers synthesized by ultrasound energy had
      better flocculation properties than the ones synthesized by the microwave
      assisted method. The biodegradability of the graft copolymers was tested by
      inoculation with the basidiomycete Trametes villosa in liquid medium. The higher
      formation of biomass than that observed with the commercial flocculant Flonex
      9045 indicated that the graft copolymer was accessible to enzymatic attack.

PMID- 29020654
TI  - Liranaftate loaded Xanthan gum based hydrogel for topical delivery: Physical
      properties and ex-vivo permeability.
AB  - A topical microemulsion (ME)-based hydrogel was developed to enhance permeation
      of an antifungal drug, liranaftate (LRFE) for effective eradication of cutaneous
      fungal infection. Pseudo-ternary phase diagrams were used to determine the
      existence of MEs region. ME formulations were prepared with Di-isopropyl
      adaptate, Cremophore-EL, Ethanol and distilled water. Xanthan Gum (1.5% w/w) was
      used for preparation of hydrogel of LRFE microemulsion (HLM) and characterized.
      The in-vitro and ex-vivo evaluation of prepared HLM and saturated drug solution
      were compared. The viscosity, average droplet size and pH of HLM were 142.30+/
      0.42 to 165.15+/-0.21Pas, 52.53-93.40nm and 6.6-7.1, respectively. Permeation
      rate of LRFE from optimized formulation (HLM-3), composed with Di-isopropyl
      adaptate (4.5% w/w), Cremophor-EL (30% w/w), Ethanol (10% w/w) and water (52%
      w/w) was observed higher in compare with other HLMs and saturated drug solution.
      HLM-3 was stable, six times higher drug deposition capacity in skin than
      saturated drug solution and did not caused any erythema based on skin sensitivity
      study on rat. The average zone of inhibition of HLM-3 (25.52+/-0.26mm) was higher
      in compare with saturated drug solution (13.44+/-0.40mm) against Candida
      albicans.

PMID- 29020655
TI  - A framework for assessing urban greenery's effects and valuing its ecosystem
      services.
AB  - Ongoing urban exploitation is increasing pressure to transform urban green
      spaces, while there is increasing awareness that greenery provides a range of
      important benefits to city residents. In efforts to help resolve associated
      problems we have developed a framework for integrated assessments of ecosystem
      service (ES) benefits and values provided by urban greenery, based on the
      ecosystem service cascade model. The aim is to provide a method for assessing the
      contribution to, and valuing, multiple ES provided by urban greenery that can be
      readily applied in routine planning processes. The framework is unique as it
      recognizes that an urban greenery comprises several components and functions that
      can contribute to multiple ecosystem services in one or more ways via different
      functional traits (e.g. foliage characteristics) for which readily measured
      indicators have been identified. The framework consists of five steps including
      compilation of an inventory of indicator; application of effectivity factors to
      rate indicators' effectiveness; estimation of effects; estimation of benefits for
      each ES; estimation of the total ES value of the ecosystem. The framework was
      applied to assess ecosystem services provided by trees, shrubs, herbs, birds, and
      bees, in green areas spanning an urban gradient in Gothenburg, Sweden. Estimates
      of perceived values of ecosystem services were obtained from interviews with the
      public and workshop activities with civil servants. The framework is systematic
      and transparent at all stages and appears to have potential utility in the
      existing spatial planning processes.

PMID- 29020656
TI  - DNA binding and in vitro anticarcinogenic activity of a series of newfashioned
      Cu(II)-complexes based on tricationic metalloporphyrin salicyloylhydrazone
      ligands.
AB  - Four novel water-soluble Cu(II) derivatives based on the meso-10, 15, 20-Tris (N
      methyl-X-pyridyl)-5-(4'-salicyloylhydrazone) metalloporphyrin ligands (X=4,
      M=Zn(1) Co(2); X=2, M=Zn(3), Co(4)), have been prepared and isolated. Various
      physicochemical techniques indicate that complex 2 interacts with calf thymus DNA
      stronger than the others through partial intercalation, suggesting that Co(II)
      has no axial ligands at porphyrin core plays a crucial role, interestingly, 2
      exhibits higher DNA binding affinity compared to 4, which could be ascribed to
      the influences of peripheral electronic effect of porphyrin ring. Cytotoxicity
      studies manifest all conjugates possess superior cytotoxicity towards non-small
      cell lung cancer (A549) and liver hepatocellular carcinoma (HepG2) but weak
      toxicity for human normal breast cells (Hs 578Bst) boiled down to the tumor
      selectivity of porphyrin. In addition, the IC50 value of 1 is lower than its
      analogues against HepG2 cells when cultivated 72h, thus the effects of
      representative complex 1 on cell morphological and cell cycle have been tailed.

PMID- 29020657
TI  - A novel approach for performing ultrasound-guided maxillary nerve block.

PMID- 29020658
TI  - Evaluation of the performance of a new automated HIV combination assay.
AB  - BACKGROUND: More and more countries test for HIV infection using combination
      assays that simultaneously detect p24 antigen and HIV antibodies. OBJECTIVE: To
      assess the performance of a new HIV combo assay: LIAISON(r) XL murex HIV Ab/Ag
      HT. STUDY DESIGN: The assays were examined with a total of 3090 samples that
      included 769 selected HIV antibody-negative samples, 1849 unselected HIV samples,
      15 HIV-1 p24 Ag reference samples, 90 primary HIV-1 infection (PHI) samples, 167
      HIV-1 antibody-positive samples (well characterized of groups M and O), 95 HIV-1
      antibody-positive samples and 105 HIV-2 antibody-positive samples. RESULTS: The
      specificity of the LIAISON(r) XL murex HIV Ab/Ag HT was 99.7%. The analytical
      sensitivity of Ag p24 of the LIAISON(r) XL murex HIV Ab/Ag HT was 0.58IU/mL and
      9.93pg/mL when using WHO and French national standards, respectively. All
      screened HIV subtypes was identified by this assay. Also, 90 PHI specimens were
      detected by this screening assay. CONCLUSION: The sensitivity and specificity of
      the LIAISON(r) XL murex HIV Ab/Ag HT assay are high. Hence the assay offers
      automated high-throughput screening with ability to detect primary infection.

PMID- 29020659
TI  - 3D gait analysis with and without an orthopedic walking boot.
AB  - INTRODUCTION: Orthopedic walking boots have been widely used in place of
      traditional fiberglass casts for a variety of orthopedic injuries and post
      surgical interventions. These walking boots create a leg length discrepancy
      (LLD). LLD has been shown to alter the kinematics and kinetics of gait and are
      associated with lumbar and lower limb conditions such as: foot over pronation,
      low back pain, scoliosis, and osteoarthritis of the hip and knee joints. Past
      gait analyses research with orthopedic boots is limited to findings on the
      ipsilateral limb. Thus, the purpose of the study was to examine bilateral gait
      kinematics & kinetics with and without a walking boot. METHODS: Forty healthy
      participants (m=20, f=20, age 20.7+/-1.8 yrs., ht. 171.6+/-9.5cm, wt. 73.2+/
      11.0kg, BMI 24.8+/-3.2) volunteered. An eight camera Vicon Motion Capture System
      with PIG model and two AMTI force plates were utilized to record the walking
      trial conditions: (1) bilateral tennis shoes (2) boot on right foot, tennis shoe
      on left foot (3) boot on right foot, barefoot on left foot. Data were processed
      in Nexus 2.2.3 and exported to Visual 3D for analysis. RESULTS: When wearing the
      boot, there were significant differences in most joint angles and moments, with
      larger effects on long limb. CONCLUSION: The walking boot alters the gait in the
      same way as those with existing LLD, putting them at risk for development of
      secondary knee, hip, and low back pain during treatment protocol.

PMID- 29020660
TI  - Identification of twenty-nine novel germline unclassified variants of BRCA1 and
      BRCA2 genes in 1400 Italian individuals.
AB  - OBJECTIVES: Breast and/or ovarian cancers are complex multifactorial diseases
      caused by interaction of both genetic and non-genetic factors and characterized
      by predisposition to inheritance. BRCA1 and BRCA2 genes are the most clinically
      involved with these kinds of cancer and the spectrum of variants affecting these
      genes is very wide. In fact, point variants, large or small insertions/deletions,
      genomic rearrangements can be found in these patients, although a large number of
      variants with uncertain biological and clinical significance continues to be
      identified. Next-generation sequencing (NGS) technology is actually the most
      powerful tool for the discovering of causative mutations and novel disease genes,
      moreover it allows to make a rapid diagnosis of genetic variants giving fast,
      inexpensive and detailed genetic information. MATERIAL AND METHODS: In this
      study, we report the screening of BRCA1 and BRCA2 genes on 1400 consecutive
      Caucasian patients with breast and/or ovarian cancer history or family risk,
      attending the oncogenetic ambulatory at the Foundation Policlinico Agostino
      Gemelli in Rome. RESULTS: We describe twenty-nine novel BRCA1 and BRCA2 variants
      detected in Italian individuals suffering from hereditary breast and ovarian
      cancer syndrome (HBOC). CONCLUSION: Data regarding novel variants can provide
      useful information not only at epidemiological but also at clinical level,
      allowing for the better managing of breast and ovarian cancer patients and their
      family members.

PMID- 29020661
TI  - Preparation and antibacterial activities of chitosan-gallic acid/polyvinyl
      alcohol blend film by LED-UV irradiation.
AB  - Active blend films from chitosan-gallic acid (CGA) and polyvinyl alcohol (PVA)
      were prepared via a simple mixing and casting method through the addition of
      citric acid as a plasticizer. The CGA/PVA blend films were characterized using
      Fourier transform infrared spectroscopy (FT-IR). The mechanical properties
      including tensile strength (TS) and elongation at break (%E), degree of
      solubility (S) and swelling behavior (DS), water vapor adsorption, and
      antimicrobial activities of the CGA/PVA blend films with and without LED (light
      emitting diode)-UV irradiation were also investigated. The CGA/PVA blend films
      exposed to UV irradiation exerted a higher TS (43.5MPa) and lower %E (50.40), S
      (0.38) and DS (2.73) compared to the CGA/PVA blend films (TS=41.7MPa, %E=55.40,
      S=0.42, and DS=3.16) not exposed LED-UV irradiation, indicating that the cross
      linkage between CGA and PVA had been strengthened by LED-UV irradiation. However,
      the water vapor adsorption in the CGA/PVA blend films increased due to the
      changes of surface roughness and pore volume after LED-UV irradiation, and all
      values increased by increasing the CGA concentrations in the CGA/PVA blend films.
      The antimicrobial activities of the CGA/PVA blend films showed that the efficient
      concentration of CGA in the CGA/PVA blend films was over 1.0%. Taken together,
      the CGA/PVA blend films have potential for use as food packing materials.

PMID- 29020662
TI  - Supercritical carbon dioxide decellularised pericardium: Mechanical and
      structural characterisation for applications in cardio-thoracic surgery.
AB  - INTRODUCTION: Many biomaterials are used in cardio-thoracic surgery with good
      short-term results. However, calcification, dehiscence, and formation of scar
      tissue are reported. The aim of this research is to characterise decellularised
      pericardium after supercritical carbon dioxide (scCO2) processing as an
      alternative biological material for uses in cardio-thoracic surgery. METHODS:
      Porcine and bovine pericardium were decellularised using scCO2. Mechanical
      properties such as tensile strength, elastic modulus, fracture toughness and
      suture retention strength were determined. Ultrastructure was visualised using
      Scanning Electron Microscopy. Water uptake and swelling was experimentally
      determined. Commercially available glutaraldehyde treated bovine pericardium was
      used as gold standard for comparison. RESULTS: scCO2 decellularised porcine (and
      bovine pericardium) maintained their tensile strength compared to untreated
      native pericardium (13.3 +/- 2.4MPa vs 14.0 +/- 4.1MPa, p = 0.73). Tensile
      strength of glutaraldehyde treated pericardium was significantly higher compared
      to untreated pericardium (19.4 +/- 7.3MPa vs 10.2 +/- 2.2MPa, p = 0.02). Suture
      retention strength of scCO2 treated pericardium was significantly higher than
      glutaraldehyde treated pericardium (p = 0.01). We found no anisotropy of scCO2 or
      glutaraldehyde treated pericardium based on a trouser tear test. Ultrastructure
      was uncompromised in scCO2 treated pericardium, while glutaraldehyde treated
      pericardium showed deterioration of extracellular matrix. CONCLUSION: scCO2
      processing preserves initial mechanical and structural properties of porcine and
      bovine pericardium, while glutaraldehyde processing damages the extracellular
      matrix of bovine pericardium. Decellularisation of tissue using scCO2 might give
      long-term solutions for cardio-thoracic surgery without compromising initial good
      mechanical properties.

PMID- 29020663
TI  - Characterization and application of azo dye (E)-N-phenyl-4-(thiazole-2
      yldiazenyl)aniline (PDA) for biomedical sterilization.
AB  - Sterilization is the certain and absolute decontamination of microorganisms
      totally from all manner of alive and active species. Sterilization devices used
      in the sterilization processes are between laboratory and external patient
      application devices of biomedical device technology, and they are designed to
      remove equipments from germs. The application potential of hetarilazo indole
      based azo dyes in the biomedical sterilization are known and azo dyes come into
      prominence in this class because of simplicity of their synthesis and procurement
      of low-cost raw materials. In this work, the application potential of a novel
      synthesized azo dye, (E)-N-phenyl-4-(thiazole-2-yldiazenyl)aniline was
      investigated as an indicator in the biomedical sterilization performing the
      electrochemical and spectroscopic characterizations. The application of indicator
      was tested by ethylene oxide, hydrogen peroxide and peracetic acid sterilization
      techniques introducing into various sterilization rolls.

PMID- 29020664
TI  - Shrinkage vectors of a flowable composite in artificial cavity models with
      different boundary conditions: Ceramic and Teflon.
AB  - Polymerization shrinkage of dental resin composites leads to stress build-up at
      the tooth-restoration interface that predisposes the restoration to debonding. In
      contrast to the heterogeneity of enamel and dentin, this study investigated the
      effect of boundary conditions in artificial cavity models such as ceramic and
      Teflon. Ceramic serves as a homogenous substrate that provides optimal bonding
      conditions, which we presented in the form of etched and silanized ceramic in
      addition to an etched, silanized and bonded ceramic cavity. In contrast, the
      Teflon cavity presented a non-adhesive boundary condition that provided an
      exaggerated condition of poor bonding as in the case of contamination during the
      application procedure or a poor bonding substrate such as sclerotic or deep
      dentin. The greatest 3D shrinkage vectors and movement in the axial direction
      were observed in the ceramic cavity with the bonding agent followed by the
      silanized ceramic cavity, and smallest shrinkage vectors and axial movements were
      observed in the Teflon cavity. The shrinkage vectors in the ceramic cavities
      exhibited downward movement toward the cavity bottom with great downward
      shrinkage of the free surface. The shrinkage vectors in the Teflon cavity pointed
      towards the center of the restoration with lateral movement greater at one side
      denoting the site of first detachment from the cavity walls. These results proved
      that the boundary conditions, in terms of bonding substrates, significantly
      influenced the shrinkage direction.

PMID- 29020665
TI  - High serum soluble CD40L levels previously to liver transplantation in patients
      with hepatocellular carcinoma are associated with mortality at one year.
AB  - PURPOSE: CD40L and its soluble form (sCD40L) are proteins of the tumor necrosis
      factor superfamily (TNFSF) that exhibit prothrombotic and proinflammatory
      properties when binding to CD40, which is a cell surface receptor of the tumor
      necrosis factor receptor superfamily (TNFRSF). High circulating levels of sCD40L
      have been associated with poor prognosis in patients with hepatocellular
      carcinoma (HCC). However, it is unknown whether there is an association between
      circulating sCD40L levels and survival in patients with HCC underwent to liver
      transplantation (LT), and this was the objective of that study. METHODS: Serum
      sCD40L levels were measured in a total of 139 patients before LT (124 survivors
      at 1year of LT and 15 non-survivors). The end-point study was 1year survival
      after liver LT. RESULTS: We found that 1-year non-surviving patients showed
      higher serum sCD40L levels than survivor patients (p=0.02). We found in logistic
      regression analysis that serum sCD40L levels higher than 321pg/mL (Odds
      Ratio=6.86; 95% confidence interval=2.06-22.76; p=0.002) and age of LT deceased
      donor were associated with death at 1year. CONCLUSIONS: The new finding of our
      study was that high serum sCD40L levels previously to LT in patients with HCC are
      associated with higher mortality at one year.

PMID- 29020667
TI  - Eye Size, Fovea, and Foraging Ecology in Accipitriform Raptors.
AB  - Birds with larger eyes are predicted to have higher spatial resolution because of
      their larger retinal image. Raptors are well known for their acute vision,
      mediated by their deep central fovea. Because foraging strategies may demand
      specific visual adaptations, eye size and fovea may differ between species with
      different foraging ecology. We tested whether predators (actively hunting mobile
      prey) and carrion eaters (eating dead prey) from the order Accipitriformes differ
      in eye size, foveal depth, and retinal thickness using spectral domain optical
      coherence tomography and comparative phylogenetic methods. We found that (1) all
      studied predators (except one) had a central and a temporal fovea, but all
      carrion eaters had only the central fovea; (2) eye size scaled with body mass
      both in predators and carrion eaters; (3) predators had larger eyes relative to
      body mass and a thicker retina at the edge of the fovea than carrion eaters, but
      there was no difference in the depth of the central fovea between the groups.
      Finally, we found that (4) larger eyes generally had a deeper central fovea.
      These results suggest that the visual system of raptors within the order
      Accipitriformes may be highly adapted to the foraging strategy, except for the
      foveal depth, which seems mostly dependent upon the eye size.

PMID- 29020666
TI  - SERS and fluorescence-based ultrasensitive detection of mercury in water.
AB  - The development of reliable and ultrasensitive detection marker for mercury ions
      (Hg2+) in drinking water is of great interest for toxicology assessment,
      environmental protection and human health. Although many Hg2+ detection methods
      have been developed, only few offer sensitivities below 1pM. Herein, we describe
      a simple histidine (H) conjugated perylene diimide (PDI) bolaamphiphile (HPH) as
      a dual-responsive optical marker to develop highly selective and sensitive probe
      as visible (sol-to-gel transformation), fluorescence and SERS-based Hg2+sensor
      platform in the water. Remarkably, HPH as a SERS marker supported on Au deposited
      monodispersed nanospheres monolayers (Au-MNM) of polystyrene offers an
      unprecedented selectivity and the best ever reported detection limit (LOD) of 60
      attomolar (aM, 0.01 parts-per-quadrillion (ppq)) for Hg2+ in water. This is ten
      orders of magnitude lower than the United States Environmental Protection Agency
      (USEPA) tolerance limit of Hg2+ in drinking water (10nM, 2 ppb). This simple and
      effective design principle of host-guest interactions driven fluorescence and
      SERS-based detection may inspire the future molecular engineering strategies for
      the development of ultrasensitive toxic analyte sensor platforms.

PMID- 29020668
TI  - [Improvement of Balance and General Physical Fitness in Older Adults by Karate: A
      Randomized Controlled Trial].

PMID- 29020669
TI  - Evidence Suggesting the End of Universal Domestic Asbestos Exposure in Metsovo,
      NW Greece.
AB  - BACKGROUND: Inhabitants of Metsovo, NW Greece, had been domestically exposed to
      asbestos from a gradually abandoned whitewash ("luto") that resulted in a
      declining epidemic of malignant mesothelioma. OBJECTIVES: We aimed to evaluate
      whether other sources of asbestos exposure exist following "luto" abandonment.
      METHODS: Chest computed tomography (CT) and bronchoalveolar lavage (BAL) were
      used to evaluate residual asbestos exposure in younger Metsovites through the
      identification of pleural calcifications and asbestos bodies, respectively. In
      order to provide a historical universally exposed group for comparison, we used
      the accumulated chest CTs and chest roentgenograms of our previous studies,
      performed in Metsovites with confirmed exposure but negative chest roentgenogram.
      As an additional external comparison group, we also assessed CT scans and chest
      roentgenograms of Metsovites being older than our target group obtained from the
      records of the Radiology Department between 2009 and 2011. In order to be able to
      compare our BAL findings, we sought historical controls among BAL studies
      performed in Metsovites with known exposure to "luto," in the 1980s-1990s, mainly
      to evaluate alveolitis. Those belonging to individuals of the same age range were
      used for further comparison. RESULTS: Twenty-two Metsovites born between 1960 and
      1980 consented to undergo a chest CT scan, while another 14 CTs were retrieved
      from the records of the Radiology Department (among 86 of all ages), thus
      increasing the number of individuals studied to 36. Five of the 36 Metsovites
      studied were former "luto" users for a short period of time. Minimal pleural
      calcifications were present in 2 of them, while all chest CTs of nonusers were
      negative. All 8 BAL studies were negative for asbestos bodies. CONCLUSION: "Luto"
      use seems to have been the only source of considerable asbestos exposure in
      Metsovo.

PMID- 29020670
TI  - Optimal Role of the Nephrologist in the Intensive Care Unit: An Intensivist's
      Opinion.

PMID- 29020672
TI  - Early Environmental Enrichment Enhances Abnormal Brain Connectivity in a Rabbit
      Model of Intrauterine Growth Restriction.
AB  - INTRODUCTION: The structural correspondence of neurodevelopmental impairments
      related to intrauterine growth restriction (IUGR) that persists later in life
      remains elusive. Moreover, early postnatal stimulation strategies have been
      proposed to mitigate these effects. Long-term brain connectivity abnormalities in
      an IUGR rabbit model and the effects of early postnatal environmental enrichment
      (EE) were explored. MATERIALS AND METHODS: IUGR was surgically induced in one
      horn, whereas the contralateral one produced the controls. Postnatally, a
      subgroup of IUGR animals was housed in an enriched environment. Functional
      assessment was performed at the neonatal and long-term periods. At the long-term
      period, structural brain connectivity was evaluated by means of diffusion
      weighted brain magnetic resonance imaging and by histological assessment focused
      on the hippocampus. RESULTS: IUGR animals displayed poorer functional results and
      presented altered whole-brain networks and decreased median fractional anisotropy
      in the hippocampus. Reduced density of dendritic spines and perineuronal nets
      from hippocampal neurons were also observed. Of note, IUGR animals exposed to
      enriched environment presented an improvement in terms of both function and
      structure. CONCLUSIONS: IUGR is associated with altered brain connectivity at the
      global and cellular level. A strategy based on early EE has the potential to
      restore the neurodevelopmental consequences of IUGR.

PMID- 29020671
TI  - Oral Lactobacillus Counts Predict Weight Gain Susceptibility: A 6-Year Follow-Up
      Study.
AB  - BACKGROUND: Recent studies have shown an association between weight change and
      the makeup of the intestinal microbiota in humans. Specifically, Lactobacillus, a
      part of the entire gastrointestinal tract's microbiota, has been shown to
      contribute to weight regulation. AIM: We examined the association between the
      level of oral Lactobacillus and the subsequent 6-year weight change in a healthy
      population of 322 Danish adults aged 35-65 years at baseline. DESIGN: Prospective
      observational study. RESULTS: In unadjusted analysis the level of oral
      Lactobacillus was inversely associated with subsequent 6-year change in BMI. A
      statistically significant interaction between the baseline level of oral
      Lactobacillus and the consumption of complex carbohydrates was found, e.g. high
      oral Lactobacillus count predicted weight loss for those with a low intake of
      complex carbohydrates, while a medium intake of complex carbohydrates predicted
      diminished weight gain. A closer examination of these relations showed that BMI
      change and Lactobacillus level was unrelated for those with high complex
      carbohydrate consumption. CONCLUSION: A high level of oral Lactobacillus seems
      related to weight loss among those with medium and low intakes of complex
      carbohydrates. Absence, or a low level of oral Lactobacillus, may potentially be
      a novel marker to identify those at increased risk of weight gain.

PMID- 29020673
TI  - Mechanism of Action of TiF4 on Dental Enamel Surface: SEM/EDX, KOH-Soluble F, and
      X-Ray Diffraction Analysis.
AB  - This in vitro study aimed to evaluate the action of TiF4 on sound and carious
      bovine and human enamel. Sound (S) and pre-demineralised (DE) bovine and human
      (primary and permanent) enamel samples were treated with TiF4 (pH 1.0) or NaF
      varnishes (pH 5.0), containing 0.95, 1.95, or 2.45% F for 12 h. The enamel
      surfaces were analysed using SEM-EDX (scanning electron microscopy/energy
      dispersive X-ray spectroscopy) (n = 10, 5 S and 5 DE) and KOH-soluble fluoride
      was quantified (n = 20, 10 S and 10 DE). Hydroxyapatite powder produced by
      precipitation method was treated with the corresponding fluoride solutions for 1
      min (n = 2). The formed compounds were detected using X-ray diffraction (XRD).
      All TiF4 varnishes produced a coating layer rich in Ti and F on all types of
      enamel surface, with micro-cracks in its extension. TiF4 (1.95 and 2.45% F)
      provided higher fluoride deposition than NaF, especially for bovine enamel (p <
      0.0001). It also induced a higher fluoride deposition on DE samples compared to S
      samples (p < 0.0001), except for primary enamel. The Ti content was higher for
      bovine and human primary enamel than human permanent enamel, with some
      differences between S and DE. The XRD analysis showed that TiF4 induced the
      formation of new compounds such as CaF2, TiO2, and Ti(HPO4)2.H2O. In conclusion,
      TiF4 (>0.95% F) interacts better, when compared to NaF, with bovine and human
      primary enamel than with human permanent enamel. TiF4 provoked higher F
      deposition compared to NaF. Carious enamel showed higher F uptake than sound
      enamel by TiF4 application, while Ti uptake was dependent on the enamel condition
      and origin.

PMID- 29020675
TI  - Increased Platelet-Monocyte Interaction in Stable COPD in the Absence of Platelet
      Hyper-Reactivity.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is well known for its
      cardiovascular co-morbidities. Increased platelet-monocyte interaction is found
      in COPD and may reflect altered platelet function and a potential role for anti
      platelet therapy. OBJECTIVES: The objectives were to investigate platelet
      monocyte interaction, platelet activation and reactivity and plasmatic
      coagulation in stable COPD. METHODS: Platelet-monocyte interaction and platelet
      activation were determined by flow cytometry in 30 stable COPD patients and 25
      controls. Platelet activation was measured by binding of fibrinogen to the
      activated fibrinogen receptor and platelet P-selectin expression at baseline and
      after platelet stimulation with platelet agonists. Plasmatic coagulation was
      measured by D-dimer and thrombin generation. RESULTS: Platelet-monocyte
      interaction was increased in stable COPD (median fluorescence intensity of
      platelet CD61 was 19.8 [IQR 14.0-33.2] vs. 10.0 [IQR 8.7-16.7], p = 0.002). In
      contrast, platelet activation and reactivity, reflected by fibrinogen binding and
      P-selectin expression, were the same in both groups. Plasma P-selectin and
      interleukin-6 were increased in COPD (p = 0.01 and p = 0.02, respectively),
      whereas soluble fibrinogen, D-dimer and thrombin generation were similar.
      CONCLUSIONS: Increased platelet-monocyte interaction was found in the absence of
      platelet hyper-reactivity and activation of plasmatic coagulation in stable COPD.
      Future clinical evaluation of the effects of different anti-platelet drugs in
      COPD is warranted, as anti-platelet therapy may interfere with platelet-monocyte
      interaction.

PMID- 29020676
TI  - Acupuncture May Improve Quality of Life in Menopausal Women: A Meta-Analysis of
      Randomized Controlled Trials.
AB  - OBJECTIVE: This analysis aims to identify, on the basis of the results of
      randomized controlled trials (RCTs), whether acupuncture therapy can alleviate
      menopausal symptoms and promote health-related quality of life. METHODS: We
      included RCTs that directly compared any type of acupuncture with sham
      acupuncture in treating menopause-related symptoms and which were published from
      January 1, 2010 to December 31, 2016 in 6 electronic databases. Two authors
      performed this work independently; 'risk-of-bias' assessment and data extraction
      were also independently performed by these 2 review authors. The outcomes are
      presented as scores of the menopause rating scale (MRS), which represents the
      self-assessment of patients. RESULTS: Six studies were included. Our analysis
      found that acupuncture can reduce the MRS score in menopausal women by the end of
      the treating period (2-3 months, on average) and even in the follow-up period (1
      3 months), not only in the total score but also in each subscale score. But the
      grade of evidence is very low. CONCLUSIONS: Both the total score and the subgroup
      analysis strongly indicated that acupuncture can alleviate menopause-related
      symptoms. However, the evidence is not very strong. Thus, further studies about
      the efficiency of acupuncture on menopausal symptoms based on well-designed
      trials are needed.

PMID- 29020674
TI  - Obesity and Type 2 Diabetes: Two Diseases with a Need for Combined Treatment
      Strategies - EASO Can Lead the Way.
AB  - Obesity is a chronic metabolic disease affecting adults and children worldwide.
      It has become one of the leading causes of death, as obesity is known to be the
      main risk factor for a number of non-communicable diseases, in particular type 2
      diabetes. This close relationship led to the connotation 'diabesity',
      highlighting the fact that the majority of individuals with diabetes are
      overweight or obese. Until today the BMI is still used to classify overweight and
      obesity. Since reduced muscle mass is highly prevalent throughout the BMI range,
      the measurement of body composition is strongly recommended. Moreover, it is
      essential for monitoring the course of weight reduction, which is part of every
      effective anti-obesity treatment. Weight reduction can be achieved via different
      weight loss strategies, including lifestyle intervention (diet and exercise),
      pharmacotherapy, or bariatric surgery. However, not all of these strategies are
      suitable for all patients, and any further needs should be considered. Besides,
      attention should also be drawn to concomitant therapies. These therapies may
      promote additional weight gain and further trigger the deterioration of blood
      glucose control. Thus, therapeutic strategies are warranted, which can be easily
      used for the management of obese patients with type 2 diabetes to achieve their
      glycemic and weight loss goals.

PMID- 29020677
TI  - The Nephrologist Has Great Potential to Have an Important Role in the Intensive
      Care Unit: Reply to the Letter to the Editor of David J.R. Morgan.

PMID- 29020678
TI  - Ovarian Cancer: A Heterogeneous Disease.
AB  - Ovarian cancer encompasses a collection of neoplasms with distinct
      clinicopathological and molecular features and prognosis. Despite there being a
      variety of ovarian cancer subtypes, these are treated as a single disease.
      Tremendous efforts have been made to characterize these subtypes and identify
      tumoral pathways and potential biomarkers for therapeutic strategies. As in other
      cancer types, tumor heterogeneity appears to be very high across subtypes and
      within a single tumor, representing a major cause of treatment failure. We
      describe the morphological and molecular heterogeneity among ovarian cancers and
      discuss recent advances in our understanding of intratumor heterogeneity.

PMID- 29020679
TI  - A Preclinical Evaluation Comparing the Performance of a Novel 19-G Flexible
      Needle to a Commercially Available 22-G EBUS-TBNA Sampling Needle.
AB  - BACKGROUND: Needle samples may not provide sufficient diagnostic material for the
      assessment of mediastinal lymph nodes. OBJECTIVE: The study compared the specimen
      size and diagnostic performance of a new 19-G endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) needle to that of a standard 22-G
      EBUS-TBNA needle in a swine model of granulomatous lymphadenopathy. METHODS:
      Granulomatous inflammation was induced in mediastinal lymph nodes (LNs) of 10
      domestic swine by injection of talc slurry. The affected LNs were sampled with
      the 19- and 22-G needles. Collected core tissue area and volume were determined
      using a specialized software and known needle internal diameter. The sample's
      quality was assessed using the biopsy core morphology grade (BCMG) as well as the
      biopsy diagnostic correlation grade (BDCG). RESULTS: There was a significant
      increase in the average LN size from baseline (11.6 +/- 3.2 to 15.2 +/- 3.8 mm; p
      < 0.001) after talc injection. A total of 132 paired samples were collected from
      38 LNs. The average mass and volume of the 19-G needle sample were larger than
      those of the 22-G needle sample: 33.78 +/- 47.48 vs. 25.18 +/- 32.08 mg (p <
      0.002) and 11.40 +/- 13.91 vs. 6.91 +/- 6.42 mm3 (p < 0.0004), respectively. The
      pooled needle biopsy samples for the 19- and the 22-G needles had similar BCMG
      (1.38 +/- 0.86 vs. 1.43 +/- 0.87, p > 0.2) and BDCG (1.54 +/- 0.93 vs. 1.57 +/-
      0.93, p > 0.2). The 19-G needle samples tended towards less blood contamination
      (p = 0.057), more often granuloma identification (46 vs. 32%, p = 0.2) and had
      more cartilage contamination (0.49 +/- 1.46 vs. 4.81 +/- 16.49% p < 0.003).
      CONCLUSION: In experienced hands, the 19- and the 22-G EBUS-TBNA needles have a
      similar diagnostic yield in the swine model of granulomatous lymphadenopathy. The
      samples collected by the 19-G needle are larger and may have less blood
      contamination.

PMID- 29020680
TI  - Hepatic T Cell Tolerance Induction in An Inflammatory Environment.
AB  - For the development of autoimmune hepatitis (AIH), genetic predisposition and
      environmental triggers are of major importance. Although experimental AIH can be
      induced in genetically susceptible mice, the low precursor frequency of
      autoreactive T cells hampers a deeper analysis of liver-specific T cells. Here,
      we established a system where the model antigen hemagglutinin (HA) is expressed
      exclusively in hepatocytes of Rosa26-HA mice following administration of a
      replication deficient adenovirus expressing Cre recombinase (Ad-Cre). Under these
      conditions, hepatocytes mimic the generation of altered-self neoantigens. To
      follow autoreactive T cells during AIH, we adoptively transferred HA--specific
      Cl4-TCR and 6.5-TCR T cells into Ad-Cre infected -Rosa26-HA mice. Alternatively,
      Rosa26-HA mice have been crossed with TCR transgenic mice that were infected with
      Ad-Cre to break hepatic tolerance and induce the expression of the HA antigen as
      a hepatic self-antigen. Surprisingly, neither adoptive transfer nor a very high
      precursor frequency of autoreactive T cells was able to break tolerance in the
      context of adenoviral infection. The low proliferation of the antigen experienced
      autoreactive T cells despite the presence of the autoantigen and inflammation
      points to anergy as a potential tolerance mechanism. This model underscores the
      crucial importance of genetic susceptibility to break tolerance against hepatic
      autoantigens.

PMID- 29020682
TI  - The Impact of Theoretical Orientation and Training on Preference for Diagnostic
      Models of Personality Pathology.
AB  - The role of theoretical orientation in determining preference for different
      methods of diagnosis has been largely unexplored. The goal of the present study
      was to explore ratings of the usefulness of 4 diagnostic methods after applying
      them to a patient: prototype ratings derived from the SWAP-II, the DSM-5 Section
      III specific personality disorders, the DSM-5 Section III trait model, and
      prototype ratings derived from the Psychodynamic Diagnostic Manual (PDM). Three
      hundred and twenty-nine trainees in APA-accredited doctoral programs and
      internships rated one of their current patients with each of the 4 diagnostic
      methods. Individuals who classified their theoretical orientation as "cognitive-
      behavioral" displayed a significantly greater preference for the proposed DSM-5
      personality disorder prototypes when compared to individuals who classified their
      orientation as "psychodynamic/psychoanalytic," while individuals who considered
      themselves psychodynamic or psychoanalytic rated the PDM as significantly more
      useful than those who considered themselves cognitive-behavioral. Individuals who
      classified their graduate program as a PsyD program were also more likely to rate
      the DSM-5 Section III and PDM models as more useful diagnostic methods than
      individuals who classified their graduate program as a PhD program. Implications
      and future directions will be discussed.

PMID- 29020683
TI  - Combination of Androgen Deprivation Therapy and Salvage Radiotherapy versus
      Salvage Radiotherapy Alone for Recurrent Prostate Cancer after Radical
      Prostatectomy.
AB  - INTRODUCTION: To assess the value of androgen deprivation therapy (ADT) on
      salvage radiotherapy (RT) in post-prostatectomy recurrent prostate cancer
      patients, we compared the oncologic outcomes between patients receiving RT + ADT
      and those receiving RT alone. MATERIALS AND METHODS: We reviewed the records of
      patients diagnosed with prostate cancer between 1995 and 2011, including 93
      patients who underwent salvage RT and 69 patients who underwent salvage RT + ADT.
      The ADT-free duration after withdrawal was calculated to verify testosterone
      recovery. RESULTS: Presalvage prostate serum antigen (PSA) was the only
      significantly different characteristic between the 2 groups (p < 0.001). The ADT
      free duration was greater than 6 months in >80% of patients. Presalvage PSA >=0.6
      ng/mL, pathologic stage >=T3b, and RT + ADT were significantly associated with
      biochemical progression after salvage treatment. RT + ADT reduced biochemical
      progression in patients with seminal vesicle invasion or presalvage PSA >=0.6
      ng/mL (p = 0.001) compared to RT alone; biochemical progression-free probability
      was unchanged in seminal vesicle noninvasive prostate cancer patients with
      presalvage PSA <0.6 ng/mL (p = 0.541). CONCLUSIONS: RT + ADT reduced the risk of
      biochemical progression after salvage treatment in patients with seminal vesicle
      invasion or presalvage PSA >=0.6 ng/mL, but had no effect in patients with
      seminal vesicle noninvasive disease and presalvage PSA <0.6 ng/mL.

PMID- 29020681
TI  - The Socioeconomic Burden of Obesity.
AB  - OBJECTIVE: To evaluate the socioeconomic impact of obesity by estimating the
      direct and indirect costs associated with obesity in Denmark, based on individual
      level data. METHODS: Costs were assessed for different BMI groups, and the
      relative risks for change in direct and indirect costs per BMI point above 30
      were estimated. A fourth analysis estimated the odds ratio for comorbidities per
      BMI point above 30. Individual data on income, social transfer payments,
      healthcare costs and diagnoses were retrieved from national registries. RESULTS:
      One BMI point above 30 was associated with a 2% decrease in income, a 3% increase
      in social transfer payments, and a 4% increase in healthcare costs. In absolute
      numbers, income contributed to most of the total economic burden. One BMI point
      above 30 was also associated with increased comorbidity, which explains the
      increase in both direct and indirect costs. CONCLUSION: Obesity is associated
      with increased comorbidity, giving rise to an increase in both direct and
      indirect costs. Especially income is affected, which emphasizes the importance of
      including both measures when evaluating the total socioeconomic burden of
      obesity. Our findings draw attention to the potential for saving public resources
      and preventing loss of income by preventing obesity.

PMID- 29020688
TI  - Follow-up of Congenital Diaphragmatic Hernia: Need for Routinary Assessment of
      Acid Gastroesophageal Reflux with pH-metry.
AB  - INTRODUCTION:  We aim to assess gastroesophageal reflux (GER) in patients treated
      for congenital diaphragmatic hernia (CDH) and to determine whether a pH-metry
      investigation should be routinely performed in follow-up. MATERIALS AND METHODS: 
      Twenty-four-hour pH-metry at 1 year was performed in all patients treated for CDH
      between January 2014 and April 2015 (Group 1). We compared pH-metry results to
      those of two other groups: children treated for esophageal atresia (EA) (Group 2)
      and normal babies presenting with typical symptoms (Group 3). All the pH-metric
      findings were analyzed and compared. Intra-group analysis was performed in Group
      1. RESULTS:  Group 1 consisted of 21, Group 2 of 24, and Group 3 of 21 patients.
      Mean pH-metry values for Groups 1, 2, and 3 were, respectively: reflux index (RI)
      4.3, 5.1, and 3.9; total number of refluxes (NR) 79.5, 88.8, and 88.7; refluxes
      longer than 5' (R > 5) 1.7, 2.3, and 1.47; and longest reflux episode (LR) 11.4,
      13.3, and 8.6. No significant differences were found between Group 1 and the
      others. Only two CDH patients presented with GER-related symptoms. Patch was
      associated with significantly higher RI (8.5 vs. 2.98, p = 0.03). The worse was
      the defect, the worse were the pH-metric results (RI: A3.09, B3.15, and C9.1).
      CONCLUSION:  We believe that a routine GER assessment should be performed in all
      CDH patients regardless the presence of symptoms. LEVEL OF EVIDENCE:  This is a
      Level II study.

PMID- 29020689
TI  - Transpancreatic precut papillotomy versus double-guidewire technique in difficult
      biliary cannulation: prospective randomized study.
AB  - BACKGROUND AND STUDY AIMS: Difficult biliary cannulation and unintentional
      pancreatic duct cannulation are thought to be important contributors to
      pancreatitis occurring after endoscopic retrograde cholangiopancreatography. Our
      aim was to compare and evaluate the rates of success and complications of
      transpancreatic precut papillotomy (TPPP) and the double-guidewire technique
      (DGT), both with prophylactic pancreatic stenting. PATIENTS AND METHODS: From
      April 2011 to March 2014, patients with difficult biliary cannulation, in whom we
      planned to first position a guidewire in the pancreatic duct, were enrolled, and
      68 patients were prospectively randomly allocated to two groups (TPPP 34, DGT
      34). We evaluated the rates of success and complications for each group. RESULTS:
      TPPP had a significantly higher success rate (94.1 %) than DGT (58.8 %). The rate
      of post-ERCP pancreatitis was 2.9 % in both groups. There was no significant
      difference between the two groups in the overall rate of complications related to
      cannulation. CONCLUSION : If biliary cannulation cannot be achieved, TPPP should
      be selected first after unintentional pancreatic duct cannulation.

PMID- 29020690
TI  - Cold-forceps avulsion with adjuvant snare-tip soft coagulation (CAST) is an
      effective and safe strategy for the management of non-lifting large laterally
      spreading colonic lesions.
AB  - BACKGROUND AND AIMS: Non-lifting large laterally spreading colorectal lesions
      (LSLs) are challenging to resect endoscopically and often necessitate surgery. A
      safe, simple technique to treat non-lifting LSLs endoscopically with robust long
      term outcomes has not been described. METHODS: In this single-center prospective
      observational study of consecutive patients referred for endoscopic mucosal
      resection (EMR) of LSLs >= 20 mm, LSLs not completely resectable by snare because
      of non-lifting underwent standardized completion of resection with cold-forceps
      avulsion and adjuvant snare-tip soft coagulation (CAST). Scheduled surveillance
      colonoscopies were performed at 4 - 6 months (SC1) and 18 months (SC2). Primary
      outcomes were endoscopic evidence of adenoma clearance and avoidance of surgery.
      The secondary outcome was safety. RESULTS: From January 2012 to October 2016, 540
      lifting LSLs (82.2 %) underwent complete snare excision at EMR. CAST was required
      for complete removal in 101 non-lifting LSLs (17.8 %): 63 naive non-lifting
      lesions (NNLs; 62.7 %) and 38 previously attempted non-lifting lesions (PANLs;
      37.3 %). PANLs were smaller (P < 0.001) and more likely to be non-granular (P =
      0.001) than the lifting LSLs. NNLs were of similar size (P = 0.77) and morphology
      (P = 0.10) to the lifting LSLs. CAST was successful in all cases and adverse
      events were comparable to lifting LSLs resected by complete snare excision.
      Recurrence at SC1 was comparable for PANLs (15.2 %) and lifting LSLs (15.3 %; P =
      0.99), whereas NNLs recurred more frequently (27.5 %; P = 0.049); however,
      surgery was no more common for either type of non-lifting LSL than for lifting
      LSLs. CONCLUSION: CAST is a safe, effective, and surgery-sparing therapy for the
      majority of non-lifting LSLs. It is easy to use, inexpensive, and does not
      require additional equipment.

PMID- 29020691
TI  - Erratum: Comparison of Platelet-Rich Plasma, Stromal Vascular Fraction (SVF), or
      SVF with an Injectable PLGA Nanofiber Scaffold for the Treatment of Osteochondral
      Injury in Dogs.

PMID- 29020692
TI  - Erratum: Arthritis Progression on Serial MRIs Following Diagnosis of Medial
      Meniscal Posterior Horn Root Tear.

PMID- 29020693
TI  - Barriers to Postpartum Follow-Up and Glucose Tolerance Testing in Women with
      Gestational Diabetes Mellitus.
AB  - OBJECTIVE:  This study aims to examine factors associated with postpartum follow
      up and glucose tolerance testing (GTT) in women with gestational diabetes
      mellitus (GDM). MATERIALS AND METHODS:  Case-control study of women with GDM at a
      single institution with available outpatient records (January 2008-February
      2016). Women with pregestational diabetes mellitus were excluded. The postpartum
      follow-up, GTT completion, and the reason for GTT completion failure (provider
      vs. patient noncompliance) were assessed. Bivariable and multivariable analyses
      were performed to identify factors associated with postpartum follow-up and GTT
      completion. RESULTS:  Of 683 women, 82.0% (n = 560) returned postpartum, and
      49.8% (n = 279) of those completed GTT. Women with Medicaid and late presentation
      to care were less likely to return (adjusted odds ratio [aOR]: 0.3, 95%
      confidence interval [CI]: 0.2-0.6 and aOR: 0.4, 95% CI: 0.2-0.7), but if they
      did, both factors were associated with increased odds of GTT completion (aOR:
      2.0, 95% CI: 1.3-2.9 and aOR: 3.5, 95% CI: 1.8-6.6). Patient and provider
      noncompliance contributed equally to GTT completion failure. Trainee involvement
      was associated with improved test completion (aOR: 4.6, 95% CI: 2.4-8.8).
      CONCLUSION:  The majority of women with GDM returned postpartum, but many did not
      receive recommended GTT. Public insurance and late presentation were associated
      with failure to return postpartum, but better GTT completion when a postpartum
      visit occurred. Trainee involvement was associated with improved adherence to
      screening guidelines.

PMID- 29020694
TI  - The U.S. Twin Delivery Volume and Association with Cesarean Delivery Rates: A
      Hospital-Level Analysis.
AB  - OBJECTIVE:  The objective of this study was to test whether hospitals experienced
      in twin delivery have lower rates of cesarean delivery for twins. METHODS:  We
      divided obstetric hospitals in the 2011 National Inpatient Sample by quartile of
      annual twin deliveries and compared twin cesarean delivery rates between
      hospitals with weighted linear regression. We used Pearson's coefficients to
      correlate a hospital's twin cesarean delivery rate to its overall cesarean
      delivery and vaginal birth after cesarean (VBAC) rates. RESULTS:  Annual twin
      delivery volume ranged from 1 to 506 across the 547 analyzed hospitals with a
      median of 10 and mode of 3. Adjusted rates of cesarean delivery were independent
      of delivery volume with a rate of 75.5 versus 74.8% in the lowest and highest
      volume hospitals (p = 0.09 across quartiles). A hospital's cesarean delivery rate
      for twins moderately correlated with the overall cesarean rate (r = 0.52, p <
      0.01) and inversely correlated with VBAC rate (r =  - 0.42, p < 0.01).
      CONCLUSION:  Most U.S. obstetrical units perform a low volume of twin deliveries
      with no decrease in cesarean delivery rates at higher volume hospitals. Twin
      cesarean delivery rates correlate with other obstetric parameters such as
      singleton cesarean delivery and VBAC rates suggesting twin cesarean delivery rate
      is more closely related to a hospital's general obstetric practice than its twin
      delivery volume.

PMID- 29020695
TI  - Transition to Routine Premedication for Nonemergent Intubations in a Level IV
      Neonatal Intensive Care Unit.
AB  - OBJECTIVE:  This study aims to test whether implementing a guideline for
      nonemergent intubation improves the rate of premedication for nonemergent
      intubations in an academic level IV neonatal intensive care unit (NICU). We
      further sought to test the hypothesis that neonates who receive premedication for
      a nonemergent intubation have decreased pain scores at the time of intubation,
      fewer intubation attempts, and no associated adverse events. STUDY DESIGN:  This
      was a prospective observational study with ongoing audit and feedback as well as
      statistical process control analysis. Data collection began on October 1, 2014.
      Clinical guideline implementation began in October 2015. A percent "P"-chart
      spanning seven-quarters was constructed with statistical process control analysis
      plotting premedication rates over time. Student's t-tests or Wilcoxon rank-sum
      tests were used for secondary outcomes. RESULTS:  The mean number of nonemergent
      intubations given premedications increased from 34 to 82%. The mean pain score
      was lower when premedications were given: 0.34 (95% confidence interval [CI]:
      0.10-0.58) versus 2.8 (95% CI: 1.9-3.6) (p < 0.001). The number of intubation
      attempts did not differ with premedications. CONCLUSION:  Adopting a guideline
      with supporting educational initiatives to standardize premedication before
      nonemergent intubations increased this practice. This regimen lowered clinical
      pain scores with no difference in the number of intubation attempts.

PMID- 29020696
TI  - Umbilical Cord Oxygen Content and Neonatal Morbidity at Term.
AB  - OBJECTIVE:  The objective of this study was to investigate the relationship
      between umbilical cord partial pressure of oxygen (pO2) at delivery and neonatal
      morbidity. STUDY DESIGN:  This is a secondary analysis of a prospective cohort
      study of term deliveries with universal cord gas collection between 2010 and
      2014. The primary composite outcome of neonatal morbidity included neonatal
      death, meconium aspiration syndrome, intubation, mechanical ventilation, hypoxic
      ischemic encephalopathy, and hypothermia treatment. Umbilical artery (UA), vein
      (UV), UV minus UA (Delta) pO2, and hypoxemia (pO2 <= fifth percentile) were
      compared between patients with and without neonatal morbidity. Areas under the
      receiver-operating characteristic curves were used to assess the predictive
      ability of pO2. RESULTS:  Of 7,789 patients with paired umbilical cord pO2, 106
      (1.4%) had the composite neonatal morbidity. UA pO2 was significantly lower in
      patients with neonatal morbidity compared with those without (median
      [interquartile range]: 16 (12, 21) vs. 19 (15, 24) mm Hg, p < 0.001). There was
      no difference in median UV pO2 or DeltapO2 between the groups. UA and UV
      hypoxemia were significantly more common in patients with neonatal morbidity. UA
      pO2 had limited predictive ability for neonatal morbidity (area under the curve:
      0.61, 95% confidence interval: 0.6-0.7). CONCLUSION:  Although UA pO2 is
      significantly lower in patients with neonatal morbidity, it is a poor predictor
      of neonatal morbidity at term.

PMID- 29020697
TI  - Effect of Maternal Age and Fetal Number on the Risk of Hypertensive Disorders of
      Pregnancy.
AB  - OBJECTIVE:  Our primary objective was to compare the differential contribution of
      fetal number and maternal age to the risk of hypertensive disorders of pregnancy
      (HDP). STUDY DESIGN:  This was a secondary analysis of a large study of primary
      cesarean delivery. Women with singleton, twin, or triplet gestations were
      included. Women were divided into groups based on fetal number and maternal age.
      The primary outcome was HDP. A logistic regression model was fit to adjust for
      confounders. The incidence of HDP was compared with the reference group and
      within exposure groups. RESULTS:  Of the 70,417 women included, HDP occurred in
      8,079 (12%) women. The frequency of HDP among the comparison groups ranged from
      11 to 38%. Nearly all groups had significantly increased risk of HDP compared
      with young maternal age singletons. Twin and triplet gestations increased the
      risk of HDP over singletons irrespective of maternal age after adjusting for
      baseline disease and race. The risk of HDP did not significantly increase with
      maternal age when fetal number was similar. CONCLUSION:  Fetal number
      significantly increased the risk of HDP and contributed more to that risk than
      maternal age. Maternal age became significant in groups with age greater than 40
      years.

PMID- 29020698
TI  - Norovirus outbreaks in german refugee camps in 2015.
AB  - Purpose Refugees often live in confined housing conditions with shared kitchen
      and sanitary facilities, rendering susceptible to communicable diseases. We here
      describe the outbreak, spread and self-limiting nature of a norovirus outbreak in
      a German refugee camp in the winter of 2015. Methods During a norovirus outbreak,
      data on clinical symptoms, nationality and living conditions was obtained in a
      refugee camp in northern Germany in the winter of 2015. Furthermore secondary
      data on norovirus outbreaks in 2015 was assessed. Results Amongst n = 982
      refugees, n = 36 patients (3.7 %) presented with acute norovirus gastroenteritis.
      The vast majority of cases were children, only the first patient was admitted to
      the hospital. Intensified hygiene measures were implemented on day 2 of the
      outbreak, but new cases peaked on day 21 and occurred until one month after the
      first case. Different cultural backgrounds, eating habits and hygiene standards
      amongst the refugees made it particularly challenging to implement stringent
      isolation and hygiene measures. Despite these predisposing factors, only minor
      norovirus outbreaks were reported in refugee camps in 2015. Conclusion Adults
      refugees had a low attack rate of symptomatic norovirus infection, while small
      children are at high risk. Infection spreads despite hygiene measures and camp
      sites and staff should be prepared for the particular challenges of such
      situations with a particular focus on cultural-background specific implementation
      of hygiene measures.

PMID- 29020700
TI  - A case report of delayed intra-abdominal and intra-luminal haemorrhage after
      polypectomy.
AB  - We report the case of a 70-year-old man who presented with hematochezia, anaemia,
      and severe abdominal pain 6 days after polypectomy. Contrast-enhanced ultrasound
      and computed tomography revealed no signs of free intra-abdominal air but showed
      intra-abdominal and intra-luminal bleeding. The patient was referred to
      colonoscopy in the operation room, which showed a coagula and venous bleeding at
      the polypectomy site. Emergency laparotomy was performed and revealed a large
      intra-abdominal mesocolic hematoma, which was surgically removed. The patient's
      post-operative recovery was uneventful. While few reports of splenic vessel
      rupture after colonoscopy due to traction on the splenocolic ligament have been
      published, delayed mesocolic hematoma without evidence of organ damage has not
      been reported so far. Clinicians need to be aware of these rare but life
      threatening complications following colonoscopy.

PMID- 29020699
TI  - The first homemade colonoscopy trainer.
AB  - Introduction Colonoscopy trainers have gained recognition for improving endoscopy
      skills and preparing for real procedures on humans. Unfortunately, due to their
      high price, commercial simulators are hard to obtain, especially for small
      medical centers. However, a solution might be to construct a device for
      themselves. Aim Our goal was to build a relatively cheap and easy-to-construct
      simulator for residents who want to start learning colonoscopy. Materials and
      methods The box model colonoscopy trainer was designed and constructed. The
      artificial colon was made from 2 layers of fabric and rubber rings between them.
      Velcro attached to the artificial colon and to the box, and the tarp straps that
      simulate peritoneal adhesions allow the bowel to be arranged in many different
      configurations. Moreover, some aspects of polypectomy training have been
      incorporated in the colonoscopy simulator. Results The self-constructed simulator
      was found to be an effective training device, with the total cost of parts not
      exceeding $30. Conclusions In this paper, we present the first homemade simulator
      for colonoscopy training. It offers the opportunity for skills acquisition in a
      preclinical setting.

PMID- 29020701
TI  - [Metal or plastic stents for preoperative biliary drainage in resectable
      pancreatic cancer?]

PMID- 29020702
TI  - [Acute Diplopia: Differential Diagnosis and Treatment Options].
AB  - Acute diplopia can be caused by harmless disorders of the optical system, but
      also by dangerous intracranial or intraorbital processes that lead to movement
      disorders of the eyes. It may therefore be difficult to decide whether further
      diagnostic evaluation is necessary. This article presents a short, structural
      overview of the most important differential diagnoses of acute diplopia and the
      treatment options.

PMID- 29020703
TI  - [Public Health Education in Health-Related Study Programs in Germany:
      Perspectives from Course Coordinators].
AB  - Introduction Public health education in Germany takes place in public health
      courses and in health-related study courses. We aim to provide data and knowledge
      on structure and content of health-related study courses and on cooperation
      between universities and/or Universities of Applied Sciences. Methods We
      conducted an online-based cross-sectional study (01.6. - 15.9.2015), involving 93
      universities and Universities of Applied Sciences in Germany. Herewith we
      addressed 351 study course coordinators. We included course coordinators from
      universities and Universities of Applied Sciences who were members of the German
      Association of Social Medicine and Prevention (DGSMP) or in the Association
      Universities for Health (HOGE). Results 104 course coordinators responded to the
      survey (43% men, 57% women). Among others, global health and environmental health
      are primarily taught in public health courses; ethics and psychology primarily in
      health-related study courses. Financial support for teaching and research is
      highly needed at universities and at universities of applied sciences.
      Furthermore, there is a high need of cooperation between institutions.
      Additionally, course coordinators from universities of applied sciences indicated
      a need for cooperative doctoral programs. Conclusion In Germany, competence
      criteria for teaching public health are missing. Additionally, cooperation
      between study courses needs to be developed further.

PMID- 29020704
TI  - [Current Research Activities on Person-Centered Medicine in Academic Institutes
      of General Practice in Germany and Austria].
AB  - AIM OF STUDY: Person-centered medicine (PCM) with its focus on humanistic
      biographical-oriented medicine and integrated, positive-salutogenic health is a
      central aspect in the patient-physician relationship in general practice. The
      objective of this analysis is to assess the prevalence and type of research
      project in academic institutions of general practice in Germany (Ger) and Austria
      (At) and the thematic priorities of the projects in the areas PCM, health
      promotion (HP), prevention (PRE) and conventional medicine (CM). METHODS: A
      search was conducted (September-December 2015) on the websites of 30 institutes
      and divisions of general medicine for their current research projects. The
      retrieved projects were assigned to five categories: PCM, HP, PRE, CM and others.
      Subsequently, we identified the targeted patient groups of the projects as well
      as the thematic focus in the categories PCM, HP, PRE and CM with focus on PCM and
      HP. RESULTS: 541 research projects were identified, 452 in Germany and 89 in
      Austria. Research projects were only included if they were explicitly indicated
      as research-oriented. Seventy projects addressed PCM aspects, 15 projects HP
      aspects, 32 projects PRE aspects and 396 projects CM aspects. The most frequently
      target groups in the categories PCM (24 of 70) and HP (7 of 15) were chronically
      ill patients. The most common thematic focus in PCM was communication (13 of 70)
      and in HP, physical activity (6 of 15). CONCLUSION: The vast majority of research
      projects investigated conventional medical topics. The percentage of research
      activities in the field of PCM (13%) or PCM including HP (16%) in Ger and At is
      below the European average of 20%. From our point of view, PCM and HP need to be
      implemented to a greater extent in general practice.

PMID- 29020705
TI  - Mechanical Strength of the Proximal Tibia Following Total Knee Arthroplasty: A
      Cadaveric Study of Resection Depth and Bone Density.
AB  - BACKGROUND: Tibial component failure has been a problem in total knee
      arthroplasty, it is still undetermined how tibial resection depth affects the
      strength to support a tibial component. This study examined the relationship
      between the resection depth and the bone density and the mechanical strength to
      support the tibial component. MATERIALS AND METHODS: Eight matched pairs of
      fresh, frozen cadaver lower legs were imaged with computed tomography to assess
      the bone density. A right tibia was resected at minimum resection level and a
      left tibia was resected at deep resection level. After the tibial component was
      implanted with cement on each tibia, it was loaded on a materials testing load
      frame to measure the stiffness and the load to failure. RESULTS: The average bone
      density at the minimum resection level of the tibia was significantly higher than
      at deep level (p=0.0003). The average stiffness and load to failure of the
      proximal tibia were 1105 N/mm (range 889 to 1303 N/mm) and 5626 N (range 3360 to
      9098 N). There was no statistical correlation between tibial resection depth and
      the axial stiffness (p=0.4107) or the load to failure (p=0.1487). CONCLUSIONS:
      Although the bone density at a minimum resection level was higher than that at a
      deep level, the strength to support the tibial component was not statistically
      higher at a minimum cutting level than at a deeper cutting level proportionally.
      Surgeons may not need to minimize a proximal tibial bone resection to maintain a
      stronger support for a tibial component.

PMID- 29020706
TI  - Social Media and Pediatric Scoliosis: An Analysis of Patient and Surgeon Use.
AB  - INTRODUCTION: The purpose of this observational study was to investigate and
      analyze the social media presence of both patients and surgeons in relation to
      pediatric scoliosis. First, patient Instagram (Instagram, Inc., San Francisco,
      California) posts were evaluated for 1) media format; 2) timing in relation to
      surgery; 3) tone; 4) perspective; 5) content; and 6) subject reference. To
      analyze reciprocal engagement, the presence and activity of pediatric scoliosis
      surgeons at five major academic centers were subsequently analyzed on Instagram,
      Twitter (Twitter Inc., San Francisco, California), and LinkedIn (LinkedIn
      Corporation, Sunnyvale, California). MATERIALS AND METHODS: A search of public
      Instagram profiles was performed over a one-year period from February 2016 to
      February 2017. Posts related to pediatric scoliosis were selected for analysis
      using a hashtag search with 30 related terms. A total of 982 posts were
      retrieved, with 669 posts meeting the inclusion criteria. Each post was then
      evaluated for timing, tone, perspective, and content using a categorical scoring
      system. An additional analysis was performed using academic orthopaedic
      hospitals' websites, in which the names of scoliosis surgeons were found and
      searched for on Instagram, Twitter, and LinkedIn. Their profiles were analyzed
      for level and length of activity, number of followers or connections, and
      references to clinical practice. RESULTS: A total of 669 posts related to
      scoliosis were analyzed, the majority of which were temporally related to non
      operative (74.7%) or post-operative (21.8%) settings. Patients (33.3%), friends
      and family (34.4%), and professional organizations (23.8%) were the most active
      contributors. The vast majority of posts were positive in nature (88.9 %) and
      highlighted the patient experience (79.2%), specifically related to bracing
      (33.1%), activities of daily living (31.7%), and surgical site or x-rays (25.5%).
      Of the social media sites analyzed, surgeons were found to have the highest
      presence on LinkedIn (55% have accounts with a mean of 175 connections) compared
      to Instagram (8%, 57 followers) and Twitter (33%, 61 followers). Surgeons were
      also noted to have more information regarding their practice, training, and
      clinical skills on LinkedIn. CONCLUSIONS: An analysis of Instagram posts related
      to scoliosis showed that the majority were shared by patients in the non
      operative period and overwhelmingly had a positive tone. The content of the posts
      focused mainly on brace wear, activities of daily living, and post-operative
      appearance or x-rays. This information provides further insight into what
      patients deem important regarding pediatric scoliosis care. Analysis of the
      social media presence of scoliosis surgeons showed that they have an
      underwhelming presence on Instagram and Twitter, but are more active on LinkedIn,
      a site geared more toward professional development and networking than other
      social media options.

PMID- 29020707
TI  - Surgical Skills Improvement Using a Low-Cost Laparoscopic Simulator for Ventral
      Incisional Hernia.
AB  - INTRODUCTION: Ventral incisional hernia is one of the most common procedures in
      laparoscopic surgery, however, it requires proper training before doing it in the
      operating room. We propose a low-cost mechanical simulator with a new optical
      system to learn the basic steps of the procedure and improve surgical
      laparoscopic skill. MATERIALS AND METHODS: From November 3, 2014 to January 4,
      2015, five residents and five surgeons with no prior laparoscopic experience, as
      well as two laparoscopic expert surgeons, participated in our study. They
      repeated the procedure three times per day for seven days. From January 10, 2015
      to April 21, 2015, the five trained and five non-trained residents performed
      (each) five real laparoscopic ventral or median incisional hernia repairs under
      senior supervision. Operative time, decision making capabilities, number of
      errors, laparoscopic skill, and depth perception were compared between the two
      groups. RESULTS: A multiple regression (R) model was calculated and F-test showed
      a significant relation between operative time and numbers of procedures with the
      laparoscopic simulator (p<0.001) for the resident and non-laparoscopic surgeons
      groups and a multiple R-squared = 0.9974 (highly significant) of the model. No
      statistical difference was found between residents and non-laparoscopic surgeons
      (p<0.001), but both groups reached the same level as the expert surgeons after
      intensive training. Kruskal-Wallis was used to show an increased operative time
      for non-trained group. Pearson test and t-test showed a lower number of errors
      and failure in the trained group. CONCLUSIONS: These results indicate that this
      new model of simulator could shorten the learning curve of surgical trainees for
      laparoscopic incisional hernia.

PMID- 29020708
TI  - Patient Factors Associated with Shorter Length of Stay Following Total Hip
      Arthroplasty-A Retrospective Cohort Study.
AB  - INTRODUCTION: Total hip arthroplasty (THA) is an increasingly common procedure in
      the United Kingdom and incurs vast costs, with a mean length of stay (LOS) of 5.5
      days. Reducing LOS plays a key role in improving cost-effectiveness, morbidity,
      and patient satisfaction following many orthopaedic procedures. The aim of this
      study was to identify attributes in patients with the shortest LOS following THA,
      with a view to targeting those with the potential for early discharge. MATERIALS
      AND METHODS: 1280 THA cases over one year at one institution were reviewed in a
      retrospective case note study. Of these, 131 patients had LOS=2 days. Various
      factors (age, gender, American Society of Anesthesiologists (ASA) score, primary
      diagnosis, body mass index (BMI), socio-economic status) were compared between
      this group and the rest of the cohort. Further characteristics of the short LOS
      group were also explored to identify trends for future study. RESULTS: Lower age,
      male gender, and low ASA grade were significantly associated with the short LOS
      group (all p<0.001). BMI, primary diagnosis, and socioeconomic status showed no
      significant differences. Short LOS patients were also noted to have few
      comorbidities, family at home, and independent transport. CONCLUSION: Younger
      age, male gender, and lower ASA grade are associated with early discharge
      following THA, and could be used to identify patients suitable for early
      discharge.

PMID- 29020709
TI  - AbsorbaSealTM Vascular Closure Device: A Novel Device for Hemostasis Following
      Interventional Peripheral Vascular Procedures.
AB  - INTRODUCTION: Vascular closure devices (VCDs) are designed to achieve rapid
      hemostasis during percutaneous coronary and peripheral vascular procedures.
      Studies demonstrate that VCDs improve time to hemostasis (TTH) and time to
      ambulation (TTA) in comparison to standard manual compression. The available
      products, however, typically have 13-17 steps in their application, often require
      hemostatic collagen or other agents as part of the process, and can result in
      significant scarring at the puncture site that can impact future access. The aim
      of this study was to investigate the performance of a three-step, novel VCD for
      access site TTH, short-term and long-term histology, and a first-in-man clinical
      study. MATERIALS AND METHODS: This study evaluated AbsorbaSealTM (CyndRx, LLC,
      Brentwood, Tennessee), a simple, three-step, VCD with bio-absorbable components.
      Following an institutional review board (IRB) approval, a 6-F sheath was placed
      directly into the porcine aorta, AbsorbaSealTM was used to seal the puncture
      site, and a measure of total time of deployment (TTD) and TTH was performed, as
      well as histologic evaluation at 30, 60, and 180 days. A complement activation
      test was performed to determine the potential for activation of the complement
      system as a mediator of inflammation. The test was performed by directly
      incubating the VCDs AbsorbaSealTM and Angio-SealTM (Terumo Interventional
      Systems, Tokyo, Japan) in human serum. Serum samples were removed after 30, 60,
      and 90 minutes and tested for the presence and amount of complement protein SC5b
      9. In the first in-man trial, the device was deployed in anticoagulated patients
      undergoing interventional vascular procedures. The TTH, estimated blood loss,
      patient pain scores, and procedural and follow-up complications were recorded.
      RESULTS: In the acute and chronic porcine studies, TTD averaged 25 seconds (17-29
      seconds). Vascular control was immediate, yielding a TTH of effectively zero
      seconds. Histologic evaluation demonstrated complete endothelial coverage of the
      device by 30 days without evidence of bleeding, clotting, or inflammation. At 60
      days, the significant mass of the device had dissolved and normal appearing
      collagen surrounded the devices with essentially no inflammatory response. By six
      months, all but one microscopic segment of one of the devices had been absorbed
      with normal appearing vascular endothelium, and no, or minimal, scarring
      appreciated. The complement test demonstrated that the AbsorbaSealTM had similar,
      or lower, complement concentrations than the negative controls and significantly
      less than Angio-SealTM. This supported the histologic findings of minimal to no
      inflammation. The VCD was deployed in 20 patients undergoing interventional
      vascular procedures. The mean TTH was 2.3 +/- 1.5 minutes. Estimated blood loss
      was 11.7 mL +/- 3.5 mL, and no significant hematoma was noted. Post-procedure
      pain scores were low, with a mean of 1.4 +/- 0.8 on a 0-10 pain rating scale.
      There were no perioperative complications and no adverse events at follow-up.
      CONCLUSIONS: The AbsorbaSealTM is safe and simple to use for vascular closure
      after interventional vascular procedures with favorable outcomes including a
      short TTH, minimal procedural blood loss, low postoperative pain scores, and no
      perioperative complications or adverse effects. Histologic evaluation reveals
      rapid device absorption and little scar formation both short- and long-term. A
      direct study of complement activation supports that AbsorbaSealTM evokes a
      minimal inflammatory response that is significantly less than Angioseal.

PMID- 29020710
TI  - Fluorescent Imaging Evaluation of Lidocaine Distribution Following Bier Block in
      the Upper Extremity.
AB  - INTRODUCTION: Bier block regional anesthesia has been used as an alternative to
      general anesthesia for years. Despite multiple theories and multiple techniques
      to delineate the location of the action of lidocaine during Bier block
      anesthesia, there has not been a consensus on the location of action. The purpose
      of this study was to use fluorescent imaging to further investigate the site of
      action of lidocaine during Bier block. MATERIALS AND METHODS: Three patients with
      carpal tunnel syndrome underwent open carpal tunnel release with Bier block
      anesthesia performed in the standard fashion with 1cc of Indocyanine green (IcG)
      mixed with lidocaine. Fluorescent images were obtained at the time of injection
      and after 10 minutes to allow patients to reach the level of surgical anesthesia.
      Repeated imaging was obtained at the time of completion of the procedure or at 30
      minutes of tourniquet time. RESULTS: At time 0, IcG was distributed along the
      superficial venous system of the hand and forearm. At 10 minutes, the
      distribution of IcG was within the capillary system and infiltrating the dermis.
      The distribution later saturated the capillary beds and remained present until
      release of the tourniquet. CONCLUSIONS: The authors demonstrate that some
      lidocaine action occurs at the cutaneous level during the administration of a
      Bier block. Due to limited field depth of view provided by the SPY(r) Elite
      System (Novadaq Technologies Inc., Mississauga, Canada), we are unable to draw
      any conclusions as to the distribution of the IcG or lidocaine at the level of
      the larger nerves at the site of the tourniquet.

PMID- 29020715
TI  - Diagnosis and management of polymyalgia rheumatica.
AB  - Polymyalgia rheumatica (PMR) is a common inflammatory condition of unknown
      aetiology with a prevalence of 1 in 133 in the over 50s, and a female to male
      ratio of 2:1. Symptoms develop over a matter of weeks; typically bilateral
      shoulder or pelvic girdle pain and stiffness, that is worse in the mornings.
      Associated symptoms include low-grade fever, malaise, fatigue, low mood, poor
      appetite, and weight loss. There is no specific diagnostic test for PMR but the
      usual pattern is a commensurate rise in CRP and ESR. A small proportion of PMR
      patients will have normal inflammatory markers. PMR is associated with giant cell
      arteritis (GCA). Half of patients with GCA will have some PMR symptoms and up to
      one fifth of patients with PMR will have evidence of GCA. Other conditions that
      can mimic PMR include: rheumatic disease in the elderly e.g. rheumatoid
      arthritis; inflammatory muscle diseases; thyroid disease; malignancy; infection;
      bilateral shoulder capsulitis; osteoarthritis, Parkinsonism and depressive
      illness. At diagnosis and each follow-up visit it is imperative to consider the
      potential for associated GCA. The patient should be asked about headaches, jaw
      claudication and visual disturbance. If there is any suspicion of GCA, urgent
      discussion with the rheumatologist should take place that day.

PMID- 29020716
TI  - Improving joint pain and function in osteoarthritis.
AB  - Osteoarthritis has become a major chronic pain condition. It affects more than
      10% of adults and accounts for almost 10% of health service resources. The impact
      of osteoarthritis is amplified by underuse of effective muscle strengthening
      exercises and a focus on often less effective and poorly tolerated analgesic
      therapies. Although traditionally considered to be primarily a disease of
      cartilage, there is now ample evidence that typical clinical osteoarthritis
      involves multiple tissue pathologies. Increased BMI is associated with a higher
      incidence of knee osteoarthritis. Anatomical abnormalities such as valgus
      alignment or previous joint trauma including meniscectomy, anterior cruciate
      ligament rupture and fracture through the joint are also associated with
      increased incidence of osteoarthritis. Pain is the main presenting symptom.
      However, we still have a poor understanding of the causes of pain in
      osteoarthritis. In patients aged 45 or over the diagnosis should be made
      clinically without investigations if the patient has activity-related joint pain
      in addition to early morning joint stiffness lasting less than 30 minutes. Muscle
      strengthening and aerobic exercise have been shown to improve joint pain and
      function. Weight loss not only improves joint pain and function but has a myriad
      of other health benefits, reducing the incidence of lifestyle associated diseases
      such as cardiovascular disease and type 2 diabetes, and mechanical stress on the
      joints.

PMID- 29020717
TI  - Ulnar nerve injury on removal of a contraceptive implant.
AB  - The close proximity of contraceptive implant placement to the course of the ulnar
      nerve can result in injury. Several factors have been implicated in this
      complication including: low BMI, erroneous placement of the implant, implantation
      over the brachial groove, and migration of the implant from its original
      insertion. Clinicians should familiarise themselves with the vulnerable
      neurovascular structures in the area and refer promptly to a specialist if any
      neurological symptoms develop during placement or removal of these devices. The
      prognosis following nerve injury is related to the anatomical site,
      pathophysiological depth of injury and delay between injury and treatment. Minor
      injury (neurapraxia) results from ischaemia or oedema within the nerve. In more
      severe injuries there is axonal damage resulting in Wallerian degeneration. The
      axonal damage affects all nerve fibre subtypes and as a result there is usually
      neuropathic pain and loss of autonomic sudomotor and vasomotor function in the
      cutaneous territory of the affected nerve. Loss of these autonomic supplies
      results in disruption of function of sweat glands and blood flow regulation which
      manifests as dry erythematous skin. High-grade nerve injury with axonal
      degeneration should be suspected when there is neuropathic pain, autonomic
      dysfunction and a positive Tinel's sign (pain in the territory of the nerve
      elicited by gently tapping over the site of suspected injury). The British
      Orthopaedic Association recommends prompt referral for specialist assessment when
      there is motor or sensory dysfunction in the territory of a nerve following an
      intervention in proximity to the nerve. Early recognition and intervention may
      prevent further degeneration and improve outcomes.

PMID- 29020718
TI  - MP-MRI could improve the diagnosis of prostate cancer.

PMID- 29020719
TI  - Diagnosis and management of nephrotic syndrome.
AB  - Nephrotic syndrome is defined by a triad of clinical features: oedema,
      substantial proteinuria (> 3.5 g/24 hours) and hypoalbuminaemia (< 30 g/L). It is
      often associated with hyperlipidaemia, thromboembolism and an increased risk of
      infection. Nephrotic syndrome develops following pathological injury to renal
      glomeruli. This may be a primary problem, with a disease specific to the kidneys,
      or secondary to a systemic disorder such as diabetes mellitus. The most common
      cause in children is minimal change glomerulonephritis. In white adults,
      nephrotic syndrome is most frequently due to membranous nephropathy whereas in
      populations of African ancestry the most common cause of nephrotic syndrome is
      focal segmental glomerulosclerosis. Diabetic nephropathy is the most common
      multisystem disease that can cause nephrotic syndrome. Patients typically present
      with periorbital oedema (most noticeable in the morning) or dependent pitting
      oedema (more common later in the day). Proteinuria should be documented by a
      quantitative measurement e.g. urine protein: creatinine ratio (PCR) or albumin:
      creatinine ratio (ACR). PCR > 300-350 mg/mmol indicates nephrotic range
      proteinuria. Urgent referral to a nephrologist (ideally within 2 weeks) is
      necessary and a renal biopsy is usually performed. This will establish what form
      of glomerular disease is responsible. Additional tests may be undertaken to
      assess if nephrotic syndrome is secondary to another disorder e.g. systemic lupus
      erythematosus or amyloidosis.

PMID- 29020720
TI  - Pyelonephritis can lead to life-threatening complications.
AB  - Acute pyelonephritis is suggested by the constellation of fever (temperature >=
      38.5 degrees  C), flank pain (typically unilateral), nausea and vomiting, and
      costovertebral angle tenderness. Complaints typical of lower UTI are variably
      present. The severity of symptoms ranges from a mild pyrexial illness to life
      threatening sepsis. The diagnosis of acute pyelonephritis should be suspected on
      the basis of the history and clinical examination. If the urine dipstick is
      negative for nitrites and leukocyte esterase this does not exclude the diagnosis,
      but it should prompt a re-evaluation of the clinical features and consideration
      of other potential diagnoses. Antibiotic therapy should be initiated without
      delay; this can be modified subsequently depending on the culture result.
      Antibiotics that are typically effective in lower urinary tract infections are
      frequently inadequate in acute pyelonephritis, and more prolonged therapy is
      necessary. Review of the clinical course and urine culture results is necessary
      to ensure that the patient is improving. Patients who have not improved within
      two days of commencing antimicrobial treatment should be referred to secondary
      care unless the infecting pathogen is not susceptible to the agent originally
      used, an alternative appropriate antibiotic is available, and the patient remains
      well enough for community care.

PMID- 29020722
TI  - Editor's Introduction to This Issue (G&I 15:3, 2017).

PMID- 29020721
TI  - Artefact mimicking torsades: treat the patient not the ECG.
AB  - ECG interpretation is an essential skill in the management of the acutely unwell
      patient and in addition to history taking and physical examination has been shown
      to have a significant effect on referral patterns to cardiologists. One of the
      basic initial steps in ECG interpretation is assessment for the presence of
      artefact which if present can dramatically influence the diagnosis. The most
      common sources of artefact are tremor e.g. in Parkinson's disease, loose skin
      electrodes and electromagnetic interference from other medical devices and mobile
      phones. The Medicines and Healthcare products Regulatory Agency in the UK advises
      that mobile phones should be kept at least one metre away from equipment that is
      sensitive to electromagnetic interference. The possibility that artefact is the
      cause of the ECG appearance should always be considered if bizarre ECG changes
      are present particularly in an asymptomatic patient. The ECG should always be
      interpreted in the context of the patient's condition. If artefact is thought to
      be the cause of the ECG appearance, then any contributory factors present should
      be corrected and the ECG should be repeated before invasive investigations are
      undertaken or treatment is administered.

PMID- 29020723
TI  - Chromosomal Microarray Testing in 42 Korean Patients with Unexplained
      Developmental Delay, Intellectual Disability, Autism Spectrum Disorders, and
      Multiple Congenital Anomalies.
AB  - Chromosomal microarray (CMA) is a high-resolution, high-throughput method of
      identifying submicroscopic genomic copy number variations (CNVs). CMA has been
      established as the first-line diagnostic test for individuals with developmental
      delay (DD), intellectual disability (ID), autism spectrum disorders (ASDs), and
      multiple congenital anomalies (MCAs). CMA analysis was performed in 42 Korean
      patients who had been diagnosed with unexplained DD, ID, ASDs, and MCAs.
      Clinically relevant CNVs were discovered in 28 patients. Variants of unknown
      significance were detected in 13 patients. The diagnostic yield was high (66.7%).
      CMA is a superior diagnostic tool compared with conventional karyotyping and
      fluorescent in situ hybridization.

PMID- 29020724
TI  - Chromothripsis in Treatment Resistance in Multiple Myeloma.
AB  - Multiple myeloma (MM) is a malignant disease caused by an abnormal proliferation
      of plasma cells, of which the prognostic factors include chromosomal abnormality,
      beta-2 microglobulin, and albumin. Recently, the term chromothripsis has emerged,
      which is the massive but highly localized chromosomal rearrangement in response
      to a one-step catastrophic event. Many studies have shown an association of
      chromothripsis with the prognosis in several cancers; however, few studies have
      investigated it in MM. Here, we studied the association between chromothripsis
      like patterns and treatment resistance or prognosis. First, we analyzed nine MM
      cell lines (U266, MM.1S, RPMI8226, KMS-11, KMS-12-BM, KMS-12-PE, KMS-28-BM, KMS
      28-PE, and NCI-H929) and bone marrow samples of four patients who were diagnosed
      with MM by next-generation sequencing-based copy number variation analysis. The
      frequency of the chromothripsis-like pattern was observed in seven cell lines. We
      analyzed the treatment-induced chromothripsis-like patterns in KMS-12-BM and KMS
      12-PE cells. As a result, breakpoints and chromothripsis-like patterns were
      increased after drug treatment in the relatively resistant KMS-12-BM. We further
      analyzed the patients' results according to the therapeutic response, which was
      divided into sensitive and resistant, as suggested by the International Myeloma
      Working Group. The chromothripsis-like pattern was more frequently observed in
      the resistant group. In the sensitive group, the frequency of the chromothripsis
      like pattern decreased after treatment, whereas the resistant group showed
      increased chromothripsis-like patterns after the treatment. These results suggest
      that the chromothripsis-like pattern is associated with treatment response in MM.

PMID- 29020726
TI  - MergeReference: A Tool for Merging Reference Panels for HLA Imputation.
AB  - Recently developed computational methods allow the imputation of human leukocyte
      antigen (HLA) genes using intergenic single nucleotide polymorphism markers. To
      improve the imputation accuracy in HLA imputation, it is essential to increase
      the sample size and the diversity of alleles in the reference panel. Our
      software, MergeReference, helps achieve this goal by providing a streamlined
      pipeline for combining multiple reference panels into one.

PMID- 29020725
TI  - Genomic Analysis of miR-21-3p and Expression Pattern with Target Gene in Olive
      Flounder.
AB  - MicroRNAs (miRNAs) act as regulators of gene expression by binding to the 3'
      untranslated region (UTR) of target genes. They perform important biological
      functions in the various species. Among many miRNAs, miR-21-3p is known to serve
      vital functions in development and apoptosis in olive flounder. Using genomic and
      bioinformatic tools, evolutionary conservation of miR-21-3p was examined in
      various species, and expression pattern was analyzed in olive flounder. Conserved
      sequences (5'-CAGUCG-3') in numerous species were detected through the stem-loop
      structure of miR-21-3p. Thus, we analyzed target genes of miR-21-3p. Among them,
      3' UTR region of PPIL2 gene indicated the highest binding affinity with miR-21-3p
      based on the minimum free energy value. The PPIL2 gene showed high expression
      levels in testis tissue of the olive flounder, whereas miR-21-3p showed rather
      ubiquitous expression patterns except in testis tissue, indicating that miR-21-3p
      seems to control the PPIL2 gene expression in a complementary repression manner
      in various tissues of olive flounder. Taken together, this current study
      contributes to infer the target gene candidates for the miR-21-3p using
      bioinformatics tools. Furthermore, our data offers important information on the
      relationship between miR-21-3p and target gene for further functional study.

PMID- 29020727
TI  - Practice nurses can improve insulin uptake in type 2 diabetes.

PMID- 29020728
TI  - Diagnosing testicular lumps in primary care.
AB  - Although the incidence of testicular cancer has increased over the past few
      decades, testicular tumours are still rare and many GPs will only see one or two
      new diagnoses in their career. In one UK study, out of 845 patients who had been
      referred with testicular lumps or pain, only 33 (4%) were diagnosed with
      testicular cancer. Epididymal cysts, or spermatoceles when containing sperm, were
      the most common finding, and were found in 228 patients (27%). The second most
      common finding was hydrocele, a fluid collection between the parietal and
      visceral layers of the tunica vaginalis, which was found in 96 patients (11%).
      The vast majority (95-98%) of testicular cancers are germ cell tumours. In
      Western Europe, five-year survival for testicular cancer is approximately 95%. It
      is almost 100% for stage 1 seminomas, but falls to 48% in the poorest prognostic
      group - non-seminomatous tumours with metastases at diagnosis.When examining
      scrotal swellings, the key question is whether the lump is intra- or extra
      testicular, as palpable intra-testicular lesions are highly likely (around 90%)
      to be malignant, whereas those lying outside the testis are usually benign. NICE
      recommends that men with non-painful enlargement or change in shape or texture of
      the testis should be referred via the two-week wait cancer pathway. Any painful
      or tender mass within the body of the testis which is not suggestive of infection
      should also be referred. GPs should refer patients for an urgent ultrasound if
      they are aged 20-40 with a hydrocele; if there is uncertainty as to whether the
      mass is intra-testicular or extra-testicular; or if the testis cannot be fully
      palpated.

PMID- 29020729
TI  - Diagnosing and managing androgen deficiency in men.
AB  - Androgens play a crucial role in bone, muscle and fat metabolism, erythropoiesis
      and cognitive health. In men aged 40-79 years the incidence of biochemical
      deficiency and symptomatic hypogonadism is 2.1-5.7%. Decreased libido or reduced
      frequency and quality of erections, fatigue, irritability, infertility or a
      diminished feeling of wellbeing may be presenting complaints. However, a
      significant proportion of men with androgen deficiency will be identified when
      they present for unrelated concerns. Important factors to elicit from the history
      in addition to the presenting complaint include: a medical history of obesity,
      type 2 diabetes, systemic diseases or metabolic syndrome which all impact on
      testosterone physiology. A comprehensive medical review will identify agents
      which can cause low testosterone levels such as statins, steroids, opioids,
      dopamine antagonists and 5-alpha reductase inhibitors. Alcohol, anabolic steroids
      and illicit substance use such as marihuana can impact on testosterone levels and
      non-prescribed drug use should be routinely discussed. The mainstay of treatment
      in persisting androgen deficiency is to restore normal physiological levels of
      testosterone by using exogenous testosterone. It may take at least three to six
      weeks to notice any clinical improvement in symptoms. Men receiving testosterone
      supplementation should be followed closely and have their testosterone,
      haematocrit and PSA levels checked at three, six and twelve months after
      initiation of testosterone replacement therapy. Men should then be reviewed at
      least annually thereafter.

PMID- 29020730
TI  - Palpitations: when you hear hoof beats don't forget to think zebras.
AB  - In general practice palpitations are reported in around 8 per 1,000 persons per
      year. The differential diagnosis includes cardiac and psychiatric causes, as well
      as numerous others e.g. anaemia, hyperthyroidism, prescribed medication, caffeine
      and recreational drugs. Factors that point towards a cardiac aetiology are male
      sex, irregular heartbeat, history of heart disease, event duration > 5 minutes,
      frequent palpitations, and palpitations which occur at work or disturb sleep.
      Other clues suggesting a cardiac origin are abrupt onset and termination of
      palpitations, positional palpitations, and accompanying symptoms such as
      dizziness and presyncope. Cardiac arrhythmias are the result of enhanced
      automaticity, triggered activity or re-entry. The latter mechanism is responsible
      for the majority of clinically relevant arrhythmias, such as atrial fibrillation
      and supraventricular tachycardias. The prevalence of supraventricular tachycardia
      in the general population is around 2-3 per 1,000 persons. AV nodal re-entry
      tachycardia (AVNRT) is the most common paroxysmal supraventricular tachycardia,
      accounting for nearly two-thirds of all cases. The typical clinical presentation
      of AVNRT is a sudden onset of palpitations (98%) and/or dizziness (78%). Patients
      may present at any age and are more frequently female than male.

PMID- 29020733
TI  - How Have Health Insurers Performed Financially Under the ACA' Market Rules?
AB  - Issue: The Affordable Care Act (ACA) transformed the market for individual health
      insurance, so it is not surprising that insurers' transition was not entirely
      smooth. Insurers, with no previous experience under these market conditions, were
      uncertain how to price their products. As a result, they incurred significant
      losses. Based on this experience, some insurers have decided to leave the ACA's
      subsidized market, although others appear to be thriving. Goals: Examine the
      financial performance of health insurers selling through the ACA's marketplace
      exchanges in 2015--the market's most difficult year to date. Method: Analysis of
      financial data for 2015 reported by insurers from 48 states and D.C. to the
      Centers for Medicare and Medicaid Services. Findings and Conclusions: Although
      health insurers were profitable across all lines of business, they suffered a 10
      percent loss in 2015 on their health plans sold through the ACA's exchanges. The
      top quarter of the ACA exchange market was comfortably profitable, while the
      bottom quarter did much worse than the ACA market average. This indicates that
      some insurers were able to adapt to the ACA's new market rules much better than
      others, suggesting the ACA's new market structure is sustainable, if supported
      properly by administrative policy.

PMID- 29020734
TI  - Hey, Kids, Tobacco Can Wait.

PMID- 29020735
TI  - Protecting Student Athletes. Are states doing enough to keep student athletes
      safe from heat and head injuries?

PMID- 29020731
TI  - Clinical Risk Factors Influencing Dental Developmental Disturbances in Childhood
      Cancer Survivors.
AB  - Purpose: Although studies regarding dental developmental disturbances after
      childhood cancer treatment have increased, they have many limitations. Studies
      analyzing the significance of independent clinical risk factors with regard to
      the dental health status are also rare. We aimed to investigate the risk factors
      for dental developmental disturbances, particularly severe disturbances, in
      childhood cancer survivors (CCS). Materials and Methods: Oral examinations and
      retrospective reviews of medical and panoramic radiographs were performed for 196
      CCS (mean age, 15.6 years). Cancer type, age at diagnosis, treatment modality,
      type and accumulated dose of administered drugs, and dose and site of radiation
      were recorded. Dental developmental disturbances were diagnosed using panoramic
      radiographs and graded for severity according to the Modified Dental Defect Index
      (MDDI). Descriptive statistics and multivariate analyseswere performed to
      determine the association between dental abnormalities and clinical factors.
      Results: In total, 109 CCS (55.6%) exhibited at least one dental anomaly, and the
      median value of MDDI was 2.5. Microdontia (30.6%) was the most prevalent anomaly,
      followed by tooth agenesis (20.4%), V-shaped roots (14.8%), and taurodontism
      (10.2%). Multivariate analysis revealed that a young age at diagnosis (<= 3
      years), a history of hematopoietic stem cell transplantation, the use of multiple
      classes of chemotherapeutic agents (>= 4 classes), and the use of heavy metal
      agents were significant risk factors for severe dental disturbances. Conclusion:
      CCS with any of the above risk factors for severe developmental disturbances
      should be comprehensively followed up to minimize adverse consequences to their
      dental development and preserve their future dental health.

PMID- 29020732
TI  - Detection of Germline Mutations in Patients with Epithelial Ovarian Cancer Using
      Multi-gene Panels: Beyond BRCA1/2.
AB  - Purpose: Next-generation sequencing (NGS) allows simultaneous sequencing of
      multiple cancer susceptibility genes and may represent a more efficient and less
      expensive approach than sequential testing. We assessed the frequency of germline
      mutations in individuals with epithelial ovarian cancer (EOC), using multi-gene
      panels and NGS. Materials and Methods: Patients with EOC (n=117) with/without a
      family history of breast or ovarian cancer were recruited consecutively, from
      March 2016 toDecember 2016.GermlineDNAwas sequenced using 35-gene NGS panel, in
      order to identify mutations. Upon the detection of a genetic alteration using the
      panel, results were cross-validated using direct sequencing. Results: Thirty
      eight patients (32.5%) had 39 pathogenic or likely pathogenic mutations in eight
      genes, including BRCA1 (n=21), BRCA2 (n=10), BRIP1 (n=1), CHEK2 (n=2), MSH2
      (n=1), POLE (n=1), RAD51C (n=2), and RAD51D (n=2). Among 64 patients with a
      family history of cancer, 27 (42.2%) had 27 pathogenic or likely pathogenic
      mutations, and six (9.3%) had mutations in genes other than BRCA1/2, such as
      CHECK2, MSH2, POLE, and RAD51C. Fifty-five patients (47.0%) were identified to
      carry only variants of uncertain significance. Conclusion: Using the multi-gene
      panel test, we found that, of all patients included in our study, 32.5% had
      germline cancer-predisposing mutations. NGS was confirmed to substantially
      improve the detection rates of a wide spectrum of mutations in EOC patients
      compared with those obtained with the BRCA1/2 testing alone.

PMID- 29020738
TI  - Changing the editorial crew at the IJE.

PMID- 29020737
TI  - [Biogenesis and functions of piRNAs in the reproductive system of male mice].
AB  - PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs of 24-32
      nucleotides (nt) in length, which were first found in 2006. The piRNAs in germ
      cells interact with reproduction-specific PIWI proteins and play an important
      role in the development of the reproductive system. In the reproductive system of
      the male mouse, piRNAs arise from long single stranded precursor transcripts
      expressed in discrete genomic regions. The productions of piRNAs are termed
      primary piRNA biogenesis and secondary piRNA biogenesis. Mature piRNAs can
      silence the genome instability threat posed by mobile genetic elements called
      transposons. Furthermore, piRNAs regulate the expression of mRNAs
      transcriptionally and post-transcriptionally  in spermiogenesis. This review
      summarizes the biogenesis and key functions of piRNAs in the reproductive system
      of male mice.

PMID- 29020736
TI  - [Influence of thyroid dysfunction on male sexual and reproductive functions and
      its mechanisms].
AB  - Thyroid dysfunction may affect the body growth metabolism and the synthesis and
      secretion of sex steroids. A large number of clinical and basic studies suggest
      that thyroid hormone abnormality can cause sexual and reproductive problems.
      Patients with hyperthyroidism or hypothyroidism may develop not only premature
      ejaculation but also erectile dysfunction. The thyroid hormone level also
      influences Leydig cells, Sertoli cells, and spermatogenesis. This review focuses
      on the association of thyroid dysfunction with male premature ejaculation,
      erectile dysfunction, and infertility and its mechanisms.

PMID- 29020739
TI  - Which is worse? A comparison of ART outcome between women with primary or
      recurrent endometriomas.

PMID- 29020742
TI  - Bayes Forest: a data-intensive generator of morphological tree clones.
AB  - Detailed and realistic tree form generators have numerous applications in ecology
      and forestry. For example, the varying morphology of trees contributes
      differently to formation of landscapes, natural habitats of species, and eco
      physiological characteristics of the biosphere. Here, we present an algorithm for
      generating morphological tree "clones" based on the detailed reconstruction of
      the laser scanning data, statistical measure of similarity, and a plant growth
      model with simple stochastic rules. The algorithm is designed to produce tree
      forms, i.e., morphological clones, similar (and not identical) in respect to tree
      level structure, but varying in fine-scale structural detail. Although we opted
      for certain choices in our algorithm, individual parts may vary depending on the
      application, making it a general adaptable pipeline. Namely, we showed that a
      specific multipurpose procedural stochastic growth model can be algorithmically
      adjusted to produce the morphological clones replicated from the target
      experimentally measured tree. For this, we developed a statistical measure of
      similarity (structural distance) between any given pair of trees, which allows
      for the comprehensive comparing of the tree morphologies by means of empirical
      distributions describing the geometrical and topological features of a tree.
      Finally, we developed a programmable interface to manipulate data required by the
      algorithm. Our algorithm can be used in a variety of applications for exploration
      of the morphological potential of the growth models (both theoretical and
      experimental), arising in all sectors of plant science research.

PMID- 29020740
TI  - Positive and relaxed selection associated with flight evolution and loss in
      insect transcriptomes.
AB  - The evolution of powered flight is a major innovation that has facilitated the
      success of insects. Previously, studies of birds, bats, and insects have detected
      molecular signatures of differing selection regimes in energy-related genes
      associated with flight evolution and/or loss. Here, using DNA sequences from more
      than 1000 nuclear and mitochondrial protein-coding genes obtained from insect
      transcriptomes, we conduct a broader exploration of which gene categories display
      positive and relaxed selection at the origin of flight as well as with multiple
      independent losses of flight. We detected a number of categories of nuclear genes
      more often under positive selection in the lineage leading to the winged insects
      (Pterygota), related to catabolic processes such as proteases, as well as
      splicing-related genes. Flight loss was associated with relaxed selection
      signatures in splicing genes, mirroring the results for flight evolution. Similar
      to previous studies of flight loss in various animal taxa, we observed
      consistently higher nonsynonymous-to-synonymous substitution ratios in
      mitochondrial genes of flightless lineages, indicative of relaxed selection in
      energy-related genes. While oxidative phosphorylation genes were not detected as
      being under selection with the origin of flight specifically, they were most
      often detected as being under positive selection in holometabolous (complete
      metamorphosis) insects as compared with other insect lineages. This study
      supports some convergence in gene-specific selection pressures associated with
      flight ability, and the exploratory analysis provided some new insights into gene
      categories potentially associated with the gain and loss of flight in insects.

PMID- 29020741
TI  - The sponge microbiome project.
AB  - Marine sponges (phylum Porifera) are a diverse, phylogenetically deep-branching
      clade known for forming intimate partnerships with complex communities of
      microorganisms. To date, 16S rRNA gene sequencing studies have largely utilised
      different extraction and amplification methodologies to target the microbial
      communities of a limited number of sponge species, severely limiting comparative
      analyses of sponge microbial diversity and structure. Here, we provide an
      extensive and standardised dataset that will facilitate sponge microbiome
      comparisons across large spatial, temporal, and environmental scales. Samples
      from marine sponges (n = 3569 specimens), seawater (n = 370), marine sediments (n
      = 65) and other environments (n = 29) were collected from different locations
      across the globe. This dataset incorporates at least 268 different sponge
      species, including several yet unidentified taxa. The V4 region of the 16S rRNA
      gene was amplified and sequenced from extracted DNA using standardised
      procedures. Raw sequences (total of 1.1 billion sequences) were processed and
      clustered with (i) a standard protocol using QIIME closed-reference picking
      resulting in 39 543 operational taxonomic units (OTU) at 97% sequence identity,
      (ii) a de novo clustering using Mothur resulting in 518 246 OTUs, and (iii) a new
      high-resolution Deblur protocol resulting in 83 908 unique bacterial sequences.
      Abundance tables, representative sequences, taxonomic classifications, and
      metadata are provided. This dataset represents a comprehensive resource of sponge
      associated microbial communities based on 16S rRNA gene sequences that can be
      used to address overarching hypotheses regarding host-associated prokaryotes,
      including host specificity, convergent evolution, environmental drivers of
      microbiome structure, and the sponge-associated rare biosphere.

PMID- 29020743
TI  - Development and validation of a multi-locus DNA metabarcoding method to identify
      endangered species in complex samples.
AB  - DNA metabarcoding provides great potential for species identification in complex
      samples such as food supplements and traditional medicines. Such a method would
      aid Convention on International Trade in Endangered Species of Wild Fauna and
      Flora (CITES) enforcement officers to combat wildlife crime by preventing illegal
      trade of endangered plant and animal species. The objective of this research was
      to develop a multi-locus DNA metabarcoding method for forensic wildlife species
      identification and to evaluate the applicability and reproducibility of this
      approach across different laboratories. A DNA metabarcoding method was developed
      that makes use of 12 DNA barcode markers that have demonstrated universal
      applicability across a wide range of plant and animal taxa and that facilitate
      the identification of species in samples containing degraded DNA. The DNA
      metabarcoding method was developed based on Illumina MiSeq amplicon sequencing of
      well-defined experimental mixtures, for which a bioinformatics pipeline with user
      friendly web-interface was developed. The performance of the DNA metabarcoding
      method was assessed in an international validation trial by 16 laboratories, in
      which the method was found to be highly reproducible and sensitive enough to
      identify species present in a mixture at 1% dry weight content. The advanced
      multi-locus DNA metabarcoding method assessed in this study provides reliable and
      detailed data on the composition of complex food products, including information
      on the presence of CITES-listed species. The method can provide improved
      resolution for species identification, while verifying species with multiple DNA
      barcodes contributes to an enhanced quality assurance.

PMID- 29020744
TI  - fastBMA: scalable network inference and transitive reduction.
AB  - Inferring genetic networks from genome-wide expression data is extremely
      demanding computationally. We have developed fastBMA, a distributed, parallel,
      and scalable implementation of Bayesian model averaging (BMA) for this purpose.
      fastBMA also includes a computationally efficient module for eliminating
      redundant indirect edges in the network by mapping the transitive reduction to an
      easily solved shortest-path problem. We evaluated the performance of fastBMA on
      synthetic data and experimental genome-wide time series yeast and human datasets.
      When using a single CPU core, fastBMA is up to 100 times faster than the next
      fastest method, LASSO, with increased accuracy. It is a memory-efficient,
      parallel, and distributed application that scales to human genome-wide expression
      data. A 10 000-gene regulation network can be obtained in a matter of hours using
      a 32-core cloud cluster (2 nodes of 16 cores). fastBMA is a significant
      improvement over its predecessor ScanBMA. It is more accurate and orders of
      magnitude faster than other fast network inference methods such as the 1 based on
      LASSO. The improved scalability allows it to calculate networks from genome scale
      data in a reasonable time frame. The transitive reduction method can improve
      accuracy in denser networks. fastBMA is available as code (M.I.T. license) from
      GitHub (https://github.com/lhhunghimself/fastBMA), as part of the updated
      networkBMA Bioconductor package
      (https://www.bioconductor.org/packages/release/bioc/html/networkBMA.html) and as
      ready-to-deploy Docker images (https://hub.docker.com/r/biodepot/fastbma/).

PMID- 29020745
TI  - Transcriptional mapping of the primary somatosensory cortex upon sensory
      deprivation.
AB  - Experience-dependent plasticity (EDP) is essential for anatomical and functional
      maturation of sensory circuits during development. Although the principal
      synaptic and circuit mechanisms of EDP are increasingly well studied
      experimentally and computationally, its molecular mechanisms remain largely
      elusive. EDP can be readily studied in the rodent barrel cortex, where each
      "barrel column" preferentially represents deflections of its own principal
      whisker. Depriving select whiskers while sparing their neighbours introduces
      competition between barrel columns, ultimately leading to weakening of
      intracortical, translaminar (i.e., cortical layer (L)4-to-L2/3) feed-forward
      excitatory projections in the deprived columns. The same synapses are potentiated
      in the neighbouring spared columns. These experience-dependent alterations of
      synaptic strength are thought to underlie somatosensory map plasticity. We used
      RNA sequencing in this model system to uncover cortical-column and -layer
      specific changes on the transcriptome level that are induced by altered sensory
      experience. Column- and layer-specific barrel cortical tissues were collected
      from juvenile mice with all whiskers intact and mice that received 11-12 days of
      long whisker (C-row) deprivation before high-quality RNA was purified and
      sequenced. The current dataset entails an average of 50 million paired-end reads
      per sample, 75 base pairs in length. On average, 90.15% of reads could be
      uniquely mapped to the mm10 reference mouse genome. The current data reveal the
      transcriptional changes in gene expression in the barrel cortex upon altered
      sensory experience in juvenile mice and will help to molecularly map the
      mechanisms of cortical plasticity.

PMID- 29020746
TI  - Proteomic landscape of the primary somatosensory cortex upon sensory deprivation.
AB  - Experience-dependent plasticity (EDP) powerfully shapes neural circuits by
      inducing long-lasting molecular changes in the brain. Molecular mechanisms of EDP
      have been traditionally studied by identifying single or small subsets of targets
      along the biochemical pathways that link synaptic receptors to nuclear processes.
      Recent technological advances in large-scale analysis of gene transcription and
      translation now allow systematic observation of thousands of molecules
      simultaneously. Here we employed label-free quantitative mass spectrometry to
      address experience-dependent changes in the proteome after sensory deprivation of
      the primary somatosensory cortex. Cortical column- and layer-specific tissue
      samples were collected from control animals, with all whiskers intact, and
      animals whose C-row whiskers were bilaterally plucked for 11-14 days. Thirty
      three samples from cortical layers (L) 2/3 and L4 spanning across control,
      deprived, and first- and second-order spared columns yielded at least 10 000
      peptides mapping to ~5000 protein groups. Of these, 4676 were identified with
      high confidence, and >3000 were found in all samples. This comprehensive database
      provides a snapshot of the proteome after whisker deprivation, a protocol that
      has been widely used to unravel the synaptic, cellular, and network mechanisms of
      EDP. Complementing the recently made available transcriptome for identical
      experimental conditions (see the accompanying article by Kole et al.), the
      database can be used to (i) mine novel targets whose translation is modulated by
      sensory organ use, (ii) cross-validate experimental protocols from the same
      developmental time point, and (iii) statistically map the molecular pathways of
      cortical plasticity at a columnar and laminar resolution.

PMID- 29020747
TI  - Deep machine learning provides state-of-the-art performance in image-based plant
      phenotyping.
AB  - In plant phenotyping, it has become important to be able to measure many features
      on large image sets in order to aid genetic discovery. The size of the datasets,
      now often captured robotically, often precludes manual inspection, hence the
      motivation for finding a fully automated approach. Deep learning is an emerging
      field that promises unparalleled results on many data analysis problems. Building
      on artificial neural networks, deep approaches have many more hidden layers in
      the network, and hence have greater discriminative and predictive power. We
      demonstrate the use of such approaches as part of a plant phenotyping pipeline.
      We show the success offered by such techniques when applied to the challenging
      problem of image-based plant phenotyping and demonstrate state-of-the-art results
      (>97% accuracy) for root and shoot feature identification and localization. We
      use fully automated trait identification using deep learning to identify
      quantitative trait loci in root architecture datasets. The majority (12 out of
      14) of manually identified quantitative trait loci were also discovered using our
      automated approach based on deep learning detection to locate plant features. We
      have shown deep learning-based phenotyping to have very good detection and
      localization accuracy in validation and testing image sets. We have shown that
      such features can be used to derive meaningful biological traits, which in turn
      can be used in quantitative trait loci discovery pipelines. This process can be
      completely automated. We predict a paradigm shift in image-based phenotyping
      bought about by such deep learning approaches, given sufficient training sets.

PMID- 29020748
TI  - Combining semi-automated image analysis techniques with machine learning
      algorithms to accelerate large-scale genetic studies.
AB  - Genetic analyses of plant root systems require large datasets of extracted
      architectural traits. To quantify such traits from images of root systems,
      researchers often have to choose between automated tools (that are prone to error
      and extract only a limited number of architectural traits) or semi-automated ones
      (that are highly time consuming). We trained a Random Forest algorithm to infer
      architectural traits from automatically extracted image descriptors. The training
      was performed on a subset of the dataset, then applied to its entirety. This
      strategy allowed us to (i) decrease the image analysis time by 73% and (ii)
      extract meaningful architectural traits based on image descriptors. We also show
      that these traits are sufficient to identify the quantitative trait loci that had
      previously been discovered using a semi-automated method. We have shown that
      combining semi-automated image analysis with machine learning algorithms has the
      power to increase the throughput of large-scale root studies. We expect that such
      an approach will enable the quantification of more complex root systems for
      genetic studies. We also believe that our approach could be extended to other
      areas of plant phenotyping.

PMID- 29020751
TI  - Erratum to: Genome sequence of a rice pest, the white-backed planthopper
      (Sogatella furcifera).

PMID- 29020749
TI  - The draft genome assembly of Rhododendron delavayi Franch. var. delavayi.
AB  - Rhododendron delavayi Franch. is globally famous as an ornamental plant. Its
      distribution in southwest China covers several different habitats and
      environments. However, not much research had been conducted on Rhododendron spp.
      at the molecular level, which hinders understanding of its evolution, speciation,
      and synthesis of secondary metabolites, as well as its wide adaptability to
      different environments. Here, we report the genome assembly and gene annotation
      of R. delavayi var. delavayi (the second genome sequenced in the Ericaceae),
      which will facilitate the study of the family. The genome assembly will have
      further applications in genome-assisted cultivar breeding. The final size of the
      assembled R. delavayi var. delavayi genome (695.09 Mb) was close to the 697.94
      Mb, estimated by k-mer analysis. A total of 336.83 gigabases (Gb) of raw Illumina
      HiSeq 2000 reads were generated from 9 libraries (with insert sizes ranging from
      170 bp to 40 kb), achieving a raw sequencing depth of *482.6. After quality
      filtering, 246.06 Gb of clean reads were obtained, giving *352.55 coverage depth.
      Assembly using Platanus gave a total scaffold length of 695.09 Mb, with a contig
      N50 of 61.8 kb and a scaffold N50 of 637.83 kb. Gene prediction resulted in the
      annotation of 32 938 protein-coding genes. The genome completeness was evaluated
      by CEGMA and BUSCO and reached 95.97% and 92.8%, respectively. The gene
      annotation completeness was also evaluated by CEGMA and BUSCO and reached 97.01%
      and 87.4%, respectively. Genome annotation revealed that 51.77% of the R.
      delavayi genome is composed of transposable elements, and 37.48% of long terminal
      repeat elements (LTRs). The de novo assembled genome of R. delavayi var. delavayi
      (hereinafter referred to as R. delavayi) is the second genomic resource of the
      family Ericaceae and will provide a valuable resource for research on future
      comparative genomic studies in Rhododendron species. The availability of the R.
      delavayi genome sequence will hopefully provide a tool for scientists to tackle
      open questions regarding molecular mechanisms underlying environmental
      interactions in the genus Rhododendron, more accurately understand the
      evolutionary processes and systematics of the genus, facilitate the
      identification of genes encoding pharmaceutically important compounds, and
      accelerate molecular breeding to release elite varieties.

PMID- 29020752
TI  - Erratum to: Draft genome of the sea cucumber Apostichopus japonicus and genetic
      polymorphism among color variants.

PMID- 29020750
TI  - De novo PacBio long-read and phased avian genome assemblies correct and add to
      reference genes generated with intermediate and short reads.
AB  - Reference-quality genomes are expected to provide a resource for studying gene
      structure, function, and evolution. However, often genes of interest are not
      completely or accurately assembled, leading to unknown errors in analyses or
      additional cloning efforts for the correct sequences. A promising solution is
      long-read sequencing. Here we tested PacBio-based long-read sequencing and
      diploid assembly for potential improvements to the Sanger-based intermediate-read
      zebra finch reference and Illumina-based short-read Anna's hummingbird reference,
      2 vocal learning avian species widely studied in neuroscience and genomics. With
      DNA of the same individuals used to generate the reference genomes, we generated
      diploid assemblies with the FALCON-Unzip assembler, resulting in contigs with no
      gaps in the megabase range, representing 150-fold and 200-fold improvements over
      the current zebra finch and hummingbird references, respectively. These long-read
      and phased assemblies corrected and resolved what we discovered to be numerous
      misassemblies in the references, including missing sequences in gaps, erroneous
      sequences flanking gaps, base call errors in difficult-to-sequence regions,
      complex repeat structure errors, and allelic differences between the 2
      haplotypes. These improvements were validated by single long-genome and
      transcriptome reads and resulted for the first time in completely resolved
      protein-coding genes widely studied in neuroscience and specialized in vocal
      learning species. These findings demonstrate the impact of long reads, sequencing
      of previously difficult-to-sequence regions, and phasing of haplotypes on
      generating the high-quality assemblies necessary for understanding gene
      structure, function, and evolution.

PMID- 29020753
TI  - Erratum to: Morphometric analysis of Passiflora leaves: the relationship between
      landmarks of the vasculature and elliptical Fourier descriptors of the blade.
AB  - Background: Leaf shape among Passiflora species is spectacularly diverse.
      Underlying this diversity in leaf shape are profound changes in the patterning of
      the primary vasculature and laminar outgrowth. Each of these aspects of leaf
      morphology-vasculature and blade-provides different insights into leaf
      patterning. Results: Here, we morphometrically analyze >3300 leaves from 40
      different Passiflora species collected sequentially across the vine. Each leaf is
      measured in two different ways: using 1) 15 homologous Procrustes-adjusted
      landmarks of the vasculature, sinuses, and lobes; and 2) Elliptical Fourier
      Descriptors (EFDs), which quantify the outline of the leaf. The ability of
      landmarks, EFDs, and both datasets together are compared to determine their
      relative ability to predict species and node position within the vine. Pairwise
      correlation of x and y landmark coordinates and EFD harmonic coefficients reveals
      close associations between traits and insights into the relationship between
      vasculature and blade patterning. Conclusions: Landmarks, more reflective of the
      vasculature, and EFDs, more reflective of the blade contour, describe both
      similar and distinct features of leaf morphology. Landmarks and EFDs vary in
      ability to predict species identity and node position in the vine and exhibit a
      correlational structure (both within landmark or EFD traits and between the two
      data types) revealing constraints between vascular and blade patterning
      underlying natural variation in leaf morphology among Passiflora species.

PMID- 29020754
TI  - Erratum to: The genome of the Antarctic-endemic copepod, Tigriopus
      kingsejongensis.

PMID- 29020755
TI  - Erratum to: An improved assembly of the loblolly pine mega-genome using long-read
      single-molecule sequencing.
AB  - The 22-gigabase genome of loblolly pine (Pinus taeda) is one of the largest ever
      sequenced. The draft assembly published in 2014 was built entirely from short
      Illumina reads, with lengths ranging from 100 to 250 base pairs (bp). The
      assembly was quite fragmented, containing over 11 million contigs whose weighted
      average (N50) size was 8206 bp. To improve this result, we generated
      approximately 12-fold coverage in long reads using the Single Molecule Real Time
      sequencing technology developed at Pacific Biosciences. We assembled the long and
      short reads together using the MaSuRCA mega-reads assembly algorithm, which
      produced a substantially better assembly, P. taeda version 2.0. The new assembly
      has an N50 contig size of 25 361, more than three times as large as achieved in
      the original assembly, and an N50 scaffold size of 107 821, 61% larger than the
      previous assembly.

PMID- 29020756
TI  - Using Focus Group Interviews to Analyze the Behavior of Users of New Types of
      Tobacco Products.
AB  - Objectives: To characterize the usage patterns of new types of tobacco products
      (NTTPs) to develop effective strategies for the regulation of NTTPs in Korea.
      Methods: We conducted focus group interviews to identify the NTTP usage patterns
      of research subjects. The NTTPs were limited to electronic cigarettes (e
      cigarettes), waterpipe tobacco, and rolling tobacco. We categorized 30 research
      subjects into 4 groups. The e-cigarette group was divided into adult and
      adolescent groups. Each group contained 7-8 subjects. An interview lasting
      approximately 2 hours was conducted with each group. Results: Ninety percent of
      NTTP users used an NTTP in combination with conventional cigarettes. Subjects
      mostly bought NTTPs online, unlike how they bought cigarettes. Additionally, a
      great deal of information, such as how to use NTTPs and descriptions of NTTP
      products, was exchanged through online or offline societies. The primary reason
      why the subjects used NTTPs was that NTTPs offer a greater range of flavors and
      aromas than cigarettes. Moreover, NTTPs were felt to be less repulsive than
      cigarettes. NTTPs were not used as a cigarette substitute; rather, they were
      mostly used in places and situations where traditional cigarette smoking was not
      allowed. Conclusions: Based on the results of this study, the government should
      conduct studies on the effects of the combined use of NTTPs and cigarettes on the
      human body, obtain and provide accurate data regarding NTTP use, and develop and
      implement polices to ban NTTP advertising, which may arouse adolescents'
      curiosity, and the addition of flavoring substances to tobacco products.

PMID- 29020757
TI  - Housing Conditions Contribute to Underweight in Children: An Example From Rural
      Villages in Southeast Sulawesi, Indonesia.
AB  - Objectives: The prevalence of underweight in children under 5 years of age is
      anomalously high in Konawe District, Southeast Sulawesi Province, Indonesia. This
      state of affairs may be related to poor housing conditions, such as limited
      access to clean water, the absence of a sanitary latrine, and the use of poor
      housing materials. Therefore, this study aimed to examine the effect of housing
      conditions on underweight in under-5 children in Konawe District. Methods: This
      study was conducted in 2013 in 5 health centres in Konawe District, Southeast
      Sulawesi Province, and used a case-control study design. The study recruited 400
      under-5 children, including 100 of whom were cases and 300 of whom were age
      matched controls (1:3). Cases were underweight children, while the controls were
      children with a normal nutritional status. The independent variables were the
      availability and types of water and latrine facilities and housing materials
      (roof, wall, and floor). The statistical analysis used Cox regression. Results: A
      lack of water availability (odds ratio [OR], 5.0; 95% confidence interval [CI],
      2.7 to 9.5; p<0.001), a lack of latrine availability in the home (OR, 2.5; 95%
      CI, 1.5 to 4.0; p<0.001), and poor-quality roofing materials (OR, 1.7; 95% CI,
      1.1 to 2.7; p<0.02) significantly contributed to underweight in children. In
      contrast, the walls and the floors did not contribute to under-5 year children
      being underweight (p=0.09 and p=0.71, respectively). Conclusions: Sanitation
      facilities and roofing were identified as important factors to address in order
      to improve children's nutritional status. Children's health status was directly
      impacted by food intake via their nutritional status.

PMID- 29020758
TI  - High Level Physical Activity and Prevalence of Cardiovascular Disease Using the
      Korea National Health and Nutrition Examination Survey Data, 2007-2013.
AB  - Objectives: The purpose of our study was to evaluate the association between the
      intensity of physical activity (PA) and prevalence of cardiovascular disease
      (CVD) using Korean representative data. Methods: We analyzed 39 804 participant
      data from the Korea National Health and Nutrition Examination Survey, 2007-2013.
      Exposure variable was three levels of PA (low, medium, and high) in a week, and
      outcome variable was prevalence of CVD based on patient self-recognition and
      doctor's diagnosis. Complex logistic regression analysis was performed to
      evaluate the relationship between level of PA and CVD adjusted by body mass
      index, hypertension, hypercholesterolemia, diabetes mellitus, stress recognition,
      household income, smoking, and current drinking. The indices of association w ere
      estimated as crude prevalence odds ratio (POR), adjusted POR, and their 95%
      confidence interval (CI). All statistical analyzes were performed using complex
      sample analysis procedure of the SPSS version 23.0. Results: When all variables
      were adjusted, only high level PA in women showed a significant association with
      stroke (adjusted POR by patient's self-recognition, 0.57; 95% CI, 0.32 to 0.99,
      adjusted POR by doctor's diagnosis, 0.55; 95% CI, 0.34 to 0.87) and CVD (adjusted
      POR by doctor's diagnosis, 0.68; 95% CI, 0.48 to 0.96). Conclusions: High level
      PA in women has a significant reverse association with prevalence of stroke and
      CVD in Korea. Further study for elucidating the mechanism will be needed.

PMID- 29020759
TI  - Hazardous Alcohol Use in 2 Countries: A Comparison Between Alberta, Canada and
      Queensland, Australia.
AB  - Objectives: This article aimed to compare alcohol consumption between the
      populations of Queensland in Australia and Alberta in Canada. Furthermore, the
      associations between greater alcohol consumption and socio-demographic
      characteristics were explored in each population. Methods: Data from 2500
      participants of the 2013 Alberta Survey and the 2013 Queensland Social Survey
      were analyzed. Regression analyses were used to explore the associations between
      alcohol risk and socio-demographic characteristics. Results: A higher rate of
      hazardous alcohol use was found in Queenslanders than in Albertans. In both
      Albertans and Queenslanders, hazardous alcohol use was associated with being
      between 18 and 24 years of age. Higher income, having no religion, living alone,
      and being born in Canada were also associated with alcohol risk in Albertans;
      while in Queenslanders, hazardous alcohol use was also associated with common-law
      marital status. In addition, hazardous alcohol use was lower among respondents
      with a non-Catholic or Protestant religious affiliation. Conclusions: Younger age
      was associated with greater hazardous alcohol use in both populations. In
      addition, different socio-demographic factors were associated with hazardous
      alcohol use in each of the populations studied. Our results allowed us to
      identify the socio-demographic profiles associated with hazardous alcohol use in
      Alberta and Queensland. These profiles constitute valuable sources of information
      for local health authorities and policymakers when designing suitable preventive
      strategies targeting hazardous alcohol use. Overall, the present study highlights
      the importance of analyzing the socio-demographic factors associated with alcohol
      consumption in population-specific contexts.

PMID- 29020760
TI  - Socioeconomic Inequalities in the Oral Health of People Aged 15-40 Years in
      Kurdistan, Iran in 2015: A Cross-sectional Study.
AB  - Objectives: The aim of this study was to evaluate socioeconomic inequalities in
      the prevalence of dental caries among an urban population. Methods: This study
      was conducted among 2000 people 15-40 years of age living in Kurdistan, Iran in
      2015. Using a questionnaire, data were collected by 4 trained dental students.
      The dependent variable was the decayed, missing, and filled teeth (DMF) index.
      Using principal component analysis, the socioeconomic status (SES) of families
      was determined based on their household assets. Inequality was measured using the
      concentration index; in addition, the Oaxaca analytical method was used to
      determine the contribution of various determinants to the observed inequality.
      Results: The concentration index for poor scores on the DMF index was -0.32 (95%
      confidence interval [CI], -0.40 to -0.36); thus, poor DMF indices had a greater
      concentration in groups with a low SES (p<0.001). Decomposition analysis showed
      that the mean prevalence of a poor DMF index was 43.7% (95% CI, 40.4 to 46.9%) in
      the least privileged group and 14.4% (95% CI, 9.5 to 9.2%) in the most privileged
      group. It was found that 85.8% of the gap observed between these groups was due
      to differences in sex, parents' education, and the district of residence. A poor
      DMF index was less prevalent among people with higher SES than among those with
      lower SES (odds ratio, 0.31; 95% CI, 0.19 to 0.52). Conclusions: An alarming
      degree of SES inequality in oral health status was found in the studied
      community. Hence, it is suggested that inequalities in oral health status be
      reduced via adopting appropriate policies such as the delivery of oral health
      services to poorer groups and covering such services in insurance programs.

PMID- 29020761
TI  - Level of Agreement and Factors Associated With Discrepancies Between Nationwide
      Medical History Questionnaires and Hospital Claims Data.
AB  - Objectives: The objectives of this study were to investigate the agreement
      between medical history questionnaire data and claims data and to identify the
      factors that were associated with discrepancies between these data types.
      Methods: Data from self-reported questionnaires that assessed an individual's
      history of hypertension, diabetes mellitus, dyslipidemia, stroke, heart disease,
      and pulmonary tuberculosis were collected from a general health screening
      database for 2014. Data for these diseases were collected from a healthcare
      utilization claims database between 2009 and 2014. Overall agreement,
      sensitivity, specificity, and kappa values were calculated. Multiple logistic
      regression analysis was performed to identify factors associated with
      discrepancies and was adjusted for age, gender, insurance type, insurance
      contribution, residential area, and comorbidities. Results: Agreement was highest
      between questionnaire data and claims data based on primary codes up to 1 year
      before the completion of self-reported questionnaires and was lowest for claims
      data based on primary and secondary codes up to 5 years before the completion of
      self-reported questionnaires. When comparing data based on primary codes up to 1
      year before the completion of self-reported questionnaires, the overall
      agreement, sensitivity, specificity, and kappa values ranged from 93.2 to 98.8%,
      26.2 to 84.3%, 95.7 to 99.6%, and 0.09 to 0.78, respectively. Agreement was
      excellent for hypertension and diabetes, fair to good for stroke and heart
      disease, and poor for pulmonary tuberculosis and dyslipidemia. Women, younger
      individuals, and employed individuals were most likely to under-report disease.
      Conclusions: Detailed patient characteristics that had an impact on information
      bias were identified through the differing levels of agreement.

PMID- 29020762
TI  - A Survival Analysis of Gastric or Colorectal Cancer Patients Treated With
      Surgery: Comparison of Capital and a Non-capital City.
AB  - Objectives: The objective of the present study was to compare prognosis of
      patients with gastric or colorectal cancer according to places where they
      received surgeries. Methods: The cancer patients underwent surgeries in sampled
      hospitals located in Daegu were matched 1:1 to the patients who visited sampled
      hospitals in Seoul using propensity score method. After the occurrences of death
      were examined, Kaplan-Meier method was used for survival analysis and the log
      rank test was performed to compare the survival curves. Results: A total of six
      out of 291 gastric cancer patients who had surgeries in Daegu died (2.1%) and ten
      deaths (3.4%) occurred from patients went Seoul hospitals. Out of 84 gastric
      cancer patients who had chemotherapy after surgeries in Daegu, 13 (15.5%)
      patients died while 18 (21.4%) deaths occurred among patients underwent surgeries
      in Seoul. Six deaths (6.9%) out of 87 colorectal cancer patients who had
      surgeries in Daegu were reported. Five patients (5.7%) died among the patients
      underwent surgeries in Seoul. Among the colorectal cancer patients with
      chemotherapy after surgeries, 13 patients (12.4%) who visited hospitals in Daegu
      and 14 (13.3%) patients who used medical centers in Seoul died. There were no
      significant differences according to places where patients used medical services.
      Conclusions: The result of this study is expected to be used as basic data for
      policy making to resolve centralization problem of cancer patients and to help
      patients to make rational choices in selection of medical centers.

PMID- 29020763
TI  - Efficacy of Precut Endoscopic Mucosal Resection for Treatment of Rectal
      Neuroendocrine Tumors.
AB  - BACKGROUND/AIMS: Endoscopic resection is the first-line treatment for rectal
      neuroendocrine tumors (NETs) measuring <1 cm and those between 1 and 2 cm in
      size. However, conventional endoscopic resection cannot achieve complete
      resection in all cases. We aimed to analyze clinical outcomes of precut
      endoscopic mucosal resection (EMR-P) used for the management of rectal NET.
      METHODS: EMR-P was used to treat rectal NET in 72 patients at a single tertiary
      center between 2011 and 2015. Both, circumferential precutting and EMR were
      performed with the same snare device in all patients. Demographics, procedural
      details, and histopathological features were reviewed for all cases. RESULTS:
      Mean size of the tumor measured endoscopically was 6.8+/-2.8 mm. En bloc and
      complete resection was achieved in 71 (98.6%) and 67 patients (93.1%),
      respectively. The mean time required for resection was 9.0+/-5.6 min. Immediate
      and delayed bleeding developed in six (8.3%) and 4 patients (5.6%), respectively.
      Immediate bleeding observed during EMR-P was associated with the risk of delayed
      bleeding. CONCLUSIONS: Both, the en bloc and complete resection rates of EMR-P in
      the treatment of rectal NETs using the same snare for precutting and EMR were
      noted to be high. The procedure was short and safe. EMR-P may be a good treatment
      choice for the management of rectal NETs.

PMID- 29020764
TI  - Incidence and risk factors for tenofovir-associated nephrotoxicity among human
      immunodeficiency virus-infected patients in Korea.
AB  - Background/Aims: Little is known about tenofovir disoproxil fumarate (TDF)
      induced nephrotoxicity in human immunodeficiency virus (HIV)-infected patients in
      Korea. The objective of this study was to evaluate the incidence and risk factors
      of TDF-associated nephrotoxicity among HIV-infected patients in Korea. Methods: A
      single-center retrospective cohort study was conducted on HIVinfected patients in
      Korea. We included patients who had started TDF or abacavir (ABC)-based
      antiretroviral therapy (ART) between October 2006 and December 2014. Estimated
      glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease
      Epidemiology Collaboration equation. Renal dysfunction was defined as > 25%
      decrease of baseline eGFR. A propensity matched case-control study was conducted
      to compare renal dysfunction rates between the two groups. The risk factors of
      nephrotoxicity were analyzed by Cox regression analysis. Results: A total of 210
      HIV-infected patients were included in the study, of which, 108 were TDF-based
      ART group and 102 were ABC-based ART group. Renal dysfunction occurred in 16
      patients (14.8%) in the TDF group and 11 (10.8%) in the ABC group. Incidence of
      renal dysfunction of TDF and ABC group was 9.66 per 100 person-years (PYs) and
      5.14 per 100 PYs, respectively (p = 0.176). In propensityscore-matched analysis,
      renal dysfunction rates were TDF 13.3% versus ABC 13.3% (p > 0.999). In
      multivariable analysis, Centers for Disease Control and Prevention clinical
      category C was a significant risk factor for renal dysfunction. Conclusions:
      Approximately, 13% of HIV-infected patients treated with TDF had renal
      dysfunction. Advanced stage of HIV infection was a significant risk factor for
      renal dysfunction.

PMID- 29020765
TI  - Insulin resistance is an independent predictor of erectile dysfunction in
      patients with gout.
AB  - Background/Aims: Gout is associated with metabolic disorders that are important
      risk factors for cardiovascular disease and erectile dysfunction (ED). We aimed
      to identify independent predictors of ED in patients with gout. Methods: From
      August 2014 to August 2015, male outpatients who were being treated for gout in
      our rheumatology clinic and healthy males without any history of inflammatory
      disease (control group) were studied. ED was assessed in participants using the
      five-item version of the International Index of Erectile Function questionnaire.
      Insulin resistance (IR) was estimated using the homeostatic model assessment
      (HOMA-IR). Logistic regression analysis was performed to determine the effect of
      variables on ED risk in all of the study subjects and in patients with gout.
      Results: We analyzed 80 patients with gout and 70 healthy controls. The median
      age of patients with gout was 52 years and median disease duration was 120
      months. Gout patients were more likely to have ED than controls (55.3% vs. 41.4%,
      p < 0.047). After adjustment for confounding factors, only HOMA-IR was
      significantly associated with ED (odds ratio [OR], 1.82; 95% confidence interval
      [CI], 1.05 to 3.15). Gout patients with ED were more likely to be older (p <
      0.001), have higher HOMA-IR (p = 0.048), and have lower glomerular filtration
      rate (p = 0.038) than those without ED. Multivariate logistic regression analysis
      showed that HOMAIR was an independent predictor for ED (OR, 1.62; 95% CI, 1.03 to
      2.82) in gout patients. Conclusions: IR is an independent predictor of ED in
      patients with gout.

PMID- 29020766
TI  - Multivalent Presentation of Cationic Peptides on Supramolecular Nanofibers for
      Antimicrobial Activity.
AB  - Noncovalent and electrostatic interactions facilitate the formation of complex
      networks through molecular self-assembly in biomolecules such as proteins and
      glycosaminoglycans. Self-assembling peptide amphiphiles (PA) are a group of
      molecules that can form nanofibrous structures and may contain bioactive epitopes
      to interact specifically with target molecules. Here, we report the presentation
      of cationic peptide sequences on supramolecular nanofibers formed by self
      assembling peptide amphiphiles for cooperative enhanced antibacterial activity.
      Antibacterial properties of self-assembled peptide nanofibers were significantly
      higher than soluble peptide molecules with identical amino acid sequences,
      suggesting that the tandem presentation of bioactive epitopes is important for
      designing new materials for bactericidal activity. In addition, bacteria were
      observed to accumulate more rapidly on peptide nanofibers compared to soluble
      peptides, which may further enhance antibacterial activity by increasing the
      number of peptide molecules interacting with the bacterial membrane. The cationic
      peptide amphiphile nanofibers were observed to attach to bacterial membranes and
      disrupt their integrity. These results demonstrate that short cationic peptides
      show a significant improvement in antibacterial activity when presented in the
      nanofiber form.

PMID- 29020768
TI  - Visible-Light-Driven Valorization of Biomass Intermediates Integrated with H2
      Production Catalyzed by Ultrathin Ni/CdS Nanosheets.
AB  - Photocatalytic upgrading of crucial biomass-derived intermediate chemicals (i.e.,
      furfural alcohol, 5-hydroxymethylfurfural (HMF)) to value-added products
      (aldehydes and acids) was carried out on ultrathin CdS nanosheets (thickness ~1
      nm) decorated with nickel (Ni/CdS). More importantly, simultaneous H2 production
      was realized upon visible light irradiation under ambient conditions utilizing
      these biomass intermediates as proton sources. The remarkable difference in the
      rates of transformation of furfural alcohol and HMF to their corresponding
      aldehydes in neutral water was observed and investigated. Aided by theoretical
      computation, it was rationalized that the slightly stronger binding affinity of
      the aldehyde group in HMF to Ni/CdS resulted in the lower transformation of HMF
      to 2,5-diformylfuran compared to that of furfural alcohol to furfural.
      Nevertheless, photocatalytic oxidation of furfural alcohol and HMF under alkaline
      conditions led to complete transformation to the respective carboxylates with
      concomitant production of H2.

PMID- 29020769
TI  - Cofacially Arrayed Polyfluorenes: Spontaneous Formation of pi-Stacked Assemblies
      in the Gas Phase.
AB  - Understanding geometrical and size dependencies of through-space charge
      delocalization in multichromophoric systems is critical to model electron
      transfer and transport in materials and biomolecules. In this work, we examine
      the size evolution of hole delocalization in van der Waals clusters of fluorene
      (i.e., (F)n), where a range of geometries are possible, reflecting both pi
      stacking and C-H/pi interactions. Using mass-selected two-color resonant two
      photon ionization spectroscopy (2CR2PI), we measure electronic spectra and
      vertical ionization potentials (IPs) in the gas phase. Results are compared with
      model covalently linked assemblies (denoted Fn), exhibiting a sterically enforced
      cofacial (i.e., pi-stacked) orientation of chromophores. For both systems, an
      inverse size dependence (i.e., 1/n) of IP vs cluster size is found. Surprisingly,
      the values for the two sets fall on the same line! This trend is examined via
      theory, which emphasizes the important role of pi-stacking, and its geometrical
      dependencies, in the process of hole delocalization in multichromophoric
      assemblies.

PMID- 29020767
TI  - Confinement of Iodine Molecules into Triple-Helical Chains within Robust Metal
      Organic Frameworks.
AB  - During nuclear waste disposal process, radioactive iodine as a fission product
      can be released. The widespread implementation of sustainable nuclear energy thus
      requires the development of efficient iodine stores that have simultaneously high
      capacity, stability and more importantly, storage density (and hence minimized
      system volume). Here, we report high I2 adsorption in a series of robust porous
      metal-organic materials, MFM-300(M) (M = Al, Sc, Fe, In). MFM-300(Sc) exhibits
      fully reversible I2 uptake of 1.54 g g-1, and its structure remains completely
      unperturbed upon inclusion/removal of I2. Direct observation and quantification
      of the adsorption, binding domains and dynamics of guest I2 molecules within
      these hosts have been achieved using XPS, TGA-MS, high resolution synchrotron X
      ray diffraction, pair distribution function analysis, Raman, terahertz and
      neutron spectroscopy, coupled with density functional theory modeling. These
      complementary techniques reveal a comprehensive understanding of the host-I2 and
      I2-I2 binding interactions at a molecular level. The initial binding site of I2
      in MFM-300(Sc), I2I, is located near the bridging hydroxyl group of the
      [ScO4(OH)2] moiety [I2I...H-O = 2.263(9) A] with an occupancy of 0.268. I2II is
      located interstitially between two phenyl rings of neighboring ligand molecules
      [I2II...phenyl ring = 3.378(9) and 4.228(5) A]. I2II is 4.565(2) A from the
      hydroxyl group with an occupancy of 0.208. Significantly, at high I2 loading an
      unprecedented self-aggregation of I2 molecules into triple-helical chains within
      the confined nanovoids has been observed at crystallographic resolution, leading
      to a highly efficient packing of I2 molecules with an exceptional I2 storage
      density of 3.08 g cm-3 in MFM-300(Sc).

PMID- 29020770
TI  - CsGOGAT Is Important in Dynamic Changes of Theanine Content in Postharvest Tea
      Plant Leaves under Different Temperature and Shading Spreadings.
AB  - We analyzed the changes of theanine content in postharvest tea leaves under high
      temperature (38  degrees C), low temperature (4  degrees C), and shading
      spreadings by using ultrahigh-performance liquid chromatography. The
      differentially expressed proteins (DEPs), CsFd-GOGAT and CsNADH-GOGAT, which are
      involved in theanine biosynthesis pathway, were identified from the corresponding
      proteome data. The protein-protein interactions of CsFd-GOGAT and CsNADH-GOGAT,
      CsTS1, or CsNiR were verified by yeast two-hybrid technology. The expression
      profiles of 17 genes in theanine metabolism, including CsFd-GOGAT and CsNADH
      GOGAT, were analyzed by quantitative real-time polymerase chain reaction. The
      correlations between the dynamic changes of theanine content and expression
      profiles of related genes and DEPs were analyzed. This study preliminarily proved
      the importance of CsGOGAT in dynamic changes of theanine content in postharvest
      tea leaves during spreading.

PMID- 29020771
TI  - Dissolution of Lignocelluloses with a High Lignin Content in a N-Methylmorpholine
      N-oxide Monohydrate Solvent System via Simple Glycerol-Swelling and Mechanical
      Pretreatments.
AB  - Lignocelluloses (LCs) with various amounts of lignin (even as high as 18.4%) were
      successfully dissolved in N-methylmorpholine-N-oxide monohydrate (NMMO/H2O)
      solution with stirring at 85  degrees C within 5 h. For the developmental
      dissolution methods of LCs with a high lignin content in NMMO/H2O solution, the
      following two pretreatment steps of LCs were necessary: (1) glycerol swelling and
      (2) mechanical extrusion. The mechanical extrusion pretreatment under glycerol
      swelling dissociated the fiber bundles of LCs to thinner fibers and, thus,
      enhanced the accessibility and solubility of the LCs in NMMO/H2O. The crystal
      structure of the pretreated LCs had no significant transformation during
      pretreatment, while the diameters of the fiber bundles were reduced from 50-60 to
      10-12 MUm, as investigated by X-ray diffraction and scanning electron microscopy.
      After the dissolution-regeneration process of LCs, the fiber bundles of the LCs
      disappeared and the crystal type of cellulose in the LCs was transformed from
      cellulose I to cellulose II, which indicated the complete dissolution of LCs.

PMID- 29020772
TI  - Genetic Constructor: An Online DNA Design Platform.
AB  - Genetic Constructor is a cloud Computer Aided Design (CAD) application developed
      to support synthetic biologists from design intent through DNA fabrication and
      experiment iteration. The platform allows users to design, manage, and navigate
      complex DNA constructs and libraries, using a new visual language that focuses on
      functional parts abstracted from sequence. Features like combinatorial libraries
      and automated primer design allow the user to separate design from construction
      by focusing on functional intent, and design constraints aid iterative refinement
      of designs. A plugin architecture enables contributions from scientists and
      coders to leverage existing powerful software and connect to DNA foundries. The
      software is easily accessible and platform agnostic, free for academics, and
      available in an open-source community edition. Genetic Constructor seeks to
      democratize DNA design, manufacture, and access to tools and services from the
      synthetic biology community.

PMID- 29020773
TI  - Electrochemical Production of Magnetite Nanoparticles for Sulfide Control in
      Sewers.
AB  - Recently, naturally occurring magnetite (Fe3O4) has emerged as a new material for
      sulfide control in sewers. However, unrefined magnetite could have high heavy
      metal contents (e.g., Cr, Zn, Ni, Sn, etc.) and the capacity to remove dissolved
      sulfide is reasonably limited due to relatively large particle sizes. To overcome
      the drawbacks of unrefined magnetite we used an electrochemical system with mild
      steel as sacrificial electrodes to in-situ generate high strength solutions of
      plate-like magnetite nanoparticles (MNP). MNP with a size range between 120 and
      160 nm were electrochemically generated at 9.35 +/- 0.28 g Fe3O4-Fe/L, resulting
      in a Coulombic efficiency (CE) for iron oxidation of 93.5 +/- 2.8%. The produced
      MNP were found to effectively reduce sulfide levels in sewage from 12.7 +/- 0.3
      to 0.2 +/- 0.0 mg S/L at a sulfide-to-MNP ratio of 0.26 g S/g Fe3O4-Fe.
      Subsequently, MNP were continuously generated with polarity switching at stable
      cell voltage for 31 days at 4.53 +/- 0.35 g Fe3O4-Fe/L with a CE for iron
      oxidation of 92.4 +/- 7.2%. The continuously produced MNP reduced sulfide at
      similar levels to around 0.2 mg S/L at a ratio of 0.28 g S/g Fe3O4-Fe.

PMID- 29020774
TI  - Core-Shell Structures Arise Naturally During Ligand Exchange in Metal-Organic
      Frameworks.
AB  - Examination of the microstructure of metal-organic frameworks (MOFs) after
      postsynthetic exchange (PSE) reveals that the exchanged ligand is concentrated at
      the edges of the crystal and decreases in concentration with crystal depth,
      resulting in a core-shell arrangement. Diffusion studies of the carboxylate
      ligand into MOF-5 indicate that diffusion is limiting to the exchange process and
      may ultimately be responsible for the observed core-shell structure. Examination
      of PSE in UMCM-8 and single crystals of UiO-66 shows a similar trend,
      illustrating the applicability of PSE as a method for the creation of core-shell
      MOFs.

PMID- 29020775
TI  - Portable Nitric Oxide (NO) Generator Based on Electrochemical Reduction of
      Nitrite for Potential Applications in Inhaled NO Therapy and Cardiopulmonary
      Bypass Surgery.
AB  - A new portable gas phase nitric oxide (NO) generator is described for potential
      applications in inhaled NO (INO) therapy and during cardiopulmonary bypass (CPB)
      surgery. In this system, NO is produced at the surface of a large-area mesh
      working electrode by electrochemical reduction of nitrite ions in the presence of
      a soluble copper(II)-ligand electron transfer mediator complex. The NO generated
      is then transported into gas phase by either direct purging with nitrogen/air or
      via circulating the electrolyte/nitrite solution through a gas extraction
      silicone fiber-based membrane-dialyzer assembly. Gas phase NO concentrations can
      be tuned in the range of 5-1000 ppm (parts per million by volume for gaseous
      species), in proportion to a constant cathodic current applied between the
      working and counter electrodes. This new NO generation process has the advantages
      of rapid production times (5 min to steady-state), high Faraday NO production
      efficiency (ca. 93%), excellent stability, and very low cost when using air as
      the carrier gas for NO (in the membrane dialyzer configuration), enabling the
      development of potentially portable INO devices. In this initial work, the new
      system is examined for the effectiveness of gaseous NO to reduce the systemic
      inflammatory response (SIR) during CPB, where 500 ppm of NO added to the sweep
      gas of the oxygenator or to the cardiotomy suction air in a CPB system is shown
      to prevent activation of white blood cells (granulocytes and monocytes) during
      extracorporeal circulation with cardiotomy suction conducted with five pigs.

PMID- 29020776
TI  - Inversion Domain Boundary Induced Stacking and Bandstructure Diversity in Bilayer
      MoSe2.
AB  - Interlayer rotation and stacking were recently demonstrated as effective
      strategies for tuning physical properties of various two-dimensional materials.
      The latter strategy was mostly realized in heterostructures with continuously
      varied stacking orders, which obscure the revelation of the intrinsic role of a
      certain stacking order in its physical properties. Here, we introduce inversion
      domain-boundaries into molecular-beam-epitaxy grown MoSe2 homobilayers, which
      induce uncommon fractional lattice translations to their surrounding domains,
      accounting for the observed diversity of large-area and uniform stacking
      sequences. Low-symmetry stacking orders were observed using scanning transmission
      electron microscopy and detailed geometries were identified by density functional
      theory. A linear relation was also revealed between interlayer distance and
      stacking energy. These stacking sequences yield various energy alignments between
      the valence states at the Gamma and K points of the Brillouin zone, showing
      stacking-dependent bandgaps and valence band tail states in the measured scanning
      tunneling spectroscopy. These results may benefit the design of two-dimensional
      multilayers with manipulable stacking orders.

PMID- 29020777
TI  - Screen-Printed PEDOT:PSS Electrodes on Commercial Finished Textiles for
      Electrocardiography.
AB  - Electrocardiography (ECG) is an essential technique for analyzing and monitoring
      cardiovascular physiological conditions such as arrhythmia. This article
      demonstrates the integration of screen-printed ECG circuitry from a commercially
      available conducting polymer, PEDOT:PSS, onto commercially available finished
      textiles. ECG signals were recorded in dry skin conditions due to the ability of
      PEDOT:PSS to function as both ionic and electronic conductors. The signal
      amplifies when the skin transpires water vapor or by applying a common lotion on
      the skin. Finally, PEDOT:PSS wires connected to PEDOT:PSS electrodes have been
      shown to record ECG signals comparable to Ag/AgCl connected to copper wires.

PMID- 29020778
TI  - [Management of Medical Termination of Pregnancy (MToP) up until the 7th week of
      gestation in the Czech Republic].
AB  - OBJECTIVE: In the Czech Republic (CR), it is possible, to carry out Medical
      Termination of Pregnancy (MToP) in the 1st trimester since June 2014, in case a
      woman submits a written request for it and in case the ultrasound examination
      confirms an intrauterine singleton prosperous pregnancy, between day 42 and 49 of
      gestation, crown-rump length (CRL) of the embryo 2-9 mm. The aim of the study is
      to analyze the management of MToP up until the 7th week of gestation in five
      centres in the CR. DESIGN: Multicenter cohort (prospective) study. SETTING:
      Department of Obstetrics and Gynecology, Palacky University Olomouc, Faculty of
      Medicine and Dentistry, University Hospital Olomouc; The Institute for the Care
      of Mother and Child, Charles University in Prague, Third faculty of Medicine;
      Department of Gynecology and Obstetrics, Charles University in Prague, First
      faculty of Medicine, General University Hospital in Prague; Department of
      Gynecology and Obstetrics, Charles University in Prague, First faculty of
      Medicine, Hospital Na Bulovce, Prague; Department of Gynecology and Obstetrics,
      Masaryk University, Faculty of Medicine, University Hospital Brno. METHODS: In
      2014-2016, a total of 1820 pregnant women requested MToP. The diagnosis of an
      intrauterine singleton prosperous pregnancy was set by transvaginal ultrasound,
      CRL 2-9 mm. MToP was carried out by combination of mifepristone (600 mg orally)
      and misoprostol (400 mcg orally) within 48 hours. MToP follow up (exclusion of
      ongoing pregnancy) after 2-3 weeks was carried out by transvaginal ultrasound as
      well. RESULTS: In 11.0% of women (201/1820) who requested MToP, CRL > 9 mm,
      unprosperous, multiple or ectopic pregnancy was diagnosed. In the remaining 1619
      women MToP was carried out, but in 221 cases (13.7%) at least one additional pre
      first visit was needed before the diagnosis of intrauterine singleton prosperous
      pregnancy CRL 2-9 mm could be established, in 19 cases (1.2%) two pre-first
      visits and in 5 cases (0.3%) even three. Gestational age was 42-49 days (average
      47.1, median 47), the women were 14-47 years of age (average 30.7, median 30). In
      20.8% of women (336/1619) MToP follow up was missed and of the remaining 1283
      women, ongoing pregnancy (MToP failure) was diagnosed in 1.6% (24/1283),
      incomplete abortion in 6.5% (83/1283) and complete abortion in 91.9% (1179/1283).
      A subsequent surgical intervention was carried out in 7.1 % of women (91/1283).
      CONCLUSION: A medical facility performing MToP in the 1st trimester should
      develop its own methodology in accordance with the legislation in force,
      Summaries of Product Characteristics, and recommendations of professional
      associations. The methodology should also include a method of evaluation of the
      result and management. The subsequent surgical intervention should only be
      performed in indicated cases. The main goal of MToP follow up is to exclude
      ongoing pregnancy (MToP failure), and the patient should be informed in detail
      about the risks involved and possibilities of their solution, it is necessary to
      obtain an informed consent.

PMID- 29020779
TI  - Management of Medical Termination of Pregnancy (MToP) up until the 7th week of
      gestation in the Czech Republic.
AB  - OBJECTIVE: In the Czech Republic (CR), it is possible, to carry out Medical
      Termination of Pregnancy (MToP) in the 1st trimester since June 2014, in case a
      woman submits a written request for it and in case the ultrasound examination
      confirms an intrauterine singleton prosperous pregnancy, between day 42 and 49 of
      gestation, crown-rump length (CRL) of the embryo 2-9 mm. The aim of the study is
      to analyze the management of MToP up until the 7th week of gestation in five
      centres in the CR. DESIGN: Multicenter cohort (prospective) study. SETTING:
      Department of Obstetrics and Gynecology, Palacky University Olomouc, Faculty of
      Medicine and Dentistry, University Hospital Olomouc; The Institute for the Care
      of Mother and Child, Charles University in Prague, Third faculty of Medicine;
      Department of Gynecology and Obstetrics, Charles University in Prague, First
      faculty of Medicine, General University Hospital in Prague; Department of
      Gynecology and Obstetrics, Charles University in Prague, First faculty of
      Medicine, Hospital Na Bulovce, Prague; Department of Gynecology and Obstetrics,
      Masaryk University, Faculty of Medicine, University Hospital Brno. METHODS: In
      2014-2016, a total of 1820 pregnant women requested MToP. The diagnosis of an
      intrauterine singleton prosperous pregnancy was set by transvaginal ultrasound,
      CRL 2-9 mm. MToP was carried out by combination of mifepristone (600 mg orally)
      and misoprostol (400 mcg orally) within 48 hours. MToP follow up (exclusion of
      ongoing pregnancy) after 2-3 weeks was carried out by transvaginal ultrasound as
      well. RESULTS: In 11.0% of women (201/1820) who requested MToP, CRL > 9 mm,
      unprosperous, multiple or ectopic pregnancy was diagnosed. In the remaining 1619
      women MToP was carried out, but in 221 cases (13.7%) at least one additional pre
      first visit was needed before the diagnosis of intrauterine singleton prosperous
      pregnancy CRL 2-9 mm could be established, in 19 cases (1.2%) two pre-first
      visits and in 5 cases (0.3%) even three. Gestational age was 42-49 days (average
      47.1, median 47), the women were 14-47 years of age (average 30.7, median 30). In
      20.8% of women (336/1619) MToP follow up was missed and of the remaining 1283
      women, ongoing pregnancy (MToP failure) was diagnosed in 1.6% (24/1283),
      incomplete abortion in 6.5% (83/1283) and complete abortion in 91.9% (1179/1283).
      A subsequent surgical intervention was carried out in 7.1 % of women (91/1283).
      CONCLUSION: A medical facility performing MToP in the 1st trimester should
      develop its own methodology in accordance with the legislation in force,
      Summaries of Product Characteristics, and recommendations of professional
      associations. The methodology should also include a method of evaluation of the
      result and management. The subsequent surgical intervention should only be
      performed in indicated cases. The main goal of MToP follow up is to exclude
      ongoing pregnancy (MToP failure), and the patient should be informed in detail
      about the risks involved and possibilities of their solution, it is necessary to
      obtain an informed consent.

PMID- 29020780
TI  - [Selective feticide in monochorionic twin pregnancies with discordant fetal
      anomalies: management and outcome].
AB  - OBJECTIVE: To analyze results and outcome after selective feticide for discordant
      anomalies in monochorionic twins. DESIGN: Prospective cohort study. SETTING:
      Fetal medicine center, Institute for the Care of Mother and Child, Praha.
      METHODS: Analysis of outcome of monochorionic pregnancies after intrauterine
      surgery for structural abnormalities between January 2013 and June 2016. RESULTS:
      We performed 13 intrauterine operations in monochorionic twins with structural
      anomalies during the period. There were 12 monochorionic diamniotic and one
      monochorionic monoamniotic twins. We encountered four cases of Twin Reversed
      Arterial Perfusion sequence (TRAP), six central nervous system lesions, two
      abdominal wall defects and one heterokaryotypic pregnancy with trisomy 13. In
      seven cases we performed bipolar cord occlusion, in four cases of TRAP sequence
      we performed radiofrequency ablation (RFA). We also performed laser
      photocoagulation of placental anastomoses in a case of gastroschisis complicated
      with twin-to-twin transfusion syndrome. One operation was unsuccessful for
      technical reasons - failing to perform amnioinfusion in a fetus with eventeration
      and anhydramnios. All procedures were performed in local anesthesia. Fetuses were
      born between 26 a 41 weeks of gestation (mean 35 weeks; 77% of fetuses were
      delivered after 32 weeks). Mean neonatal weight 2260 g. We encountered no
      intrauterine demise of a healthy fetus. CONCLUSION: Patients with discordant
      fetal anomalies in monochorionic twins can be offered a selective feticide via
      bipolar umbilical cord occlusion or radiofrequency ablation that are proven to be
      safe and effective.

PMID- 29020781
TI  - [The finding of isolated oligohydramnios after 37th week of gestation and its
      association with perinatal outcome].
AB  - OBJECTIVE: The objective of this study is to determinate the influence of
      oligohydramnios on perinatal outcome in term pregnancies. DESIGN: Retrospective
      case-control study. SETTING: II. Gynecologic Obstetrics Department, Comenius
      University, Bratislava. METHODS: Authors analysed a group of 372 single
      pregnancies after completed 37th week of gestation in years 2011 to 2015 with
      sonographic diagnosis of isolated oligohydramnios. A control group was created
      with matched patients by age and parity with normal amniotic fluid volume.
      RESULTS: We found significant differences in number of obstetric intervention
      between the two groups: patients with oligohydramnios had higher number of
      cesarean sections (71% compared to 33.9% in control group) and also the number of
      inductions was significantely higher (27.4% compared to 18.8%). The most common
      indication for cesarean delivery was presumed fetal hypoxia. We did not find any
      differences in numbers of neonates with low Apgar score, low umbilical cord pH
      and admission to neonatal intensive care unit. CONCLUSION: The finding of
      isolated oligohydramnios after 37th week of gestations is associated with higher
      risk of obstetric intervention without any association with adverse perinatal
      outcome.

PMID- 29020782
TI  - [External cephalic version after 36th week of gestationAnalysis of women's
      perspective].
AB  - OBJECTIVE: Evaluation of opinions and subjective feelings of patients who have
      undergone an external cephalic version of a fetus in breech presentation after
      the 36th week of pregnancy. DESIGN: Observational analytic cohort study. SETTING:
      Department of Obstetrics and Gynecology, Masaryk University, University Hospital
      Brno. MATERIALS AND METHODS: We collected opinions and subjective evaluation from
      pregnant women who underwent an attempt of external cephalic version at the
      department of Gynecology and Obstetrics, Masaryk University in Brno in the period
      from 1st January 2015 to 31st December 2016 through a questionnaire. The
      questionnaire contained a total of 10 dichotomous, sampling, enumeration and
      scale questions. Questions were focused on the source and type of information on
      external cephalic version, expectations of the patients, evaluation of pain and
      feelings during the procedure and the overall impression. We also evaluated the
      differences between answers from patients after a successful and an unsuccessful
      version. RESULTS: In reported period 205 pregnant women underwent an attempt of
      external cephalic version. Procedure was successful in 105 (51.2%) cases of which
      81 (77.1%) subsequently gave birth vaginally, 24 (22.9%) delivered by caesarean
      section, 10 (9.5%) out of all patients delivered in other hospitals. The total
      number of fully completed questionnaires was 187 (after a successful version 98
      and 89 after an unsuccessful version). The most common source of information
      about the procedure was given to the patients from their gynecologists (40.5%)
      and doctors at the ambulance in the hospital where the patients are sent before
      delivery by their gynecologists (27.9%). Most mothers received mostly positive
      information (70.5%) - increased likelihood of vaginal delivery, high success
      rate, low risk to mother and child. Attitude of the gynecologists on the external
      cephalic version was positive in 52.6% and they recommended it. 14.4% of the
      patients had no fear before the procedure, 61% patients were nervous and 23% had
      fear. For 30.5% of the respondents was the version worse than expected. 33.7% of
      the patients expected that the procedure would be worse and for 35.8% of the
      women the procedure fulfilled their expectations. 42.2% of all patients rated the
      pain level on a scale from 0 (no pain) to 10 (maximum pain) in the range of 4-6
      points, 28.9% evaluated the pain under 4 points and 28.9% over 6 points. Among
      other unpleasant feelings associated with external cephalic version were most
      frequently mentioned: nausea (15.9%), fear (39.8%), distress (7.5%). One-third of
      respondents, however, experienced no negative feelings (33.8%). 80.2% of the
      patients did not have any problems after the version. Out of all respondents
      89.3% would undergo the procedure again and recommend it to others. Overall
      satisfaction rating on a scale from 0 (completely dissatisfied) to 5 (very
      satisfied) was 89.8% in the range from 4 to 5. When comparing the answers of
      patients after an external cephalic version there was no significant difference
      depending on the success of the version. CONCLUSION: The results show that the
      main source of information is given to the patients by their gynecologists and
      doctors in the hospital who recommend the procedure and significantly affect the
      attitude of patients towards external cephalic version. Fear and nervousness of
      the mothers is usually unfounded, most of the women evaluate the procedure
      positively and would recommend it to another pregnant women even in case of an
      unsuccessful attempt. Pain during the procedure is for most women bearable and in
      the overall ranking does not mean a significant problem.

PMID- 29020783
TI  - [Corifollitropin alfa in women stimulated for the first time in in vitro
      fertilization programme].
AB  - OBJECTIVES: To compare results after stimulation with corifollitropin alfa
      (Elonva) in unselected group of women entering for the first time in in vitro
      fertilization programme (IVF) with results from Phase III randomized trials with
      selected groups of women. DESIGN: Prospective study. SETTING: Sanatorium
      Pronatal, Praha. METHODS: 40 unselected women with adequat ovarian reserve
      entering for the first time in IVF programme were stimulated with corifollitropin
      alfa and GnRH antagonists. Avarage age in the study group was 32,8 years (29-42
      years), women younger then 36 and less then 60 kg received Elonva 100 ug , all
      others (age > 36 let, weight > 60 kg) Elonva 150 ug. Five days after egg
      retrieval one blastocyst was transferred (single embryo transfer - eSET). Our
      results were compared with the resuls in higly selected groups of women from
      Phase III randomized trials. RESULTS: After stimulation with corifollitropin alfa
      and GnRH antagonists on average 10,6 (9,2 +/- 4,2) eggs could be retrieved, among
      them 7,3 (6,6 +/- 3,9) were M II oocytes (68,9%) and fertilisation rate was
      84,6%. After first embryo transfer ("fresh" embryos and embryos from "freeze all"
      cycles) 14 pregnancies were achieved (37,8%), three pregnancies were achieved
      later from transfer of frozen-thawed embryos (cumulative pregnancy rate 45,9%).
      There were three abortions. No severe hyperstimulation syndrom occured. Our
      results in unselected group of women stimulated for the first in an IVF programme
      with corifollitropin alfa are fully comparable with results published in
      randomized trials with selected group of patiens. CONCLUSION: Corifollitropin
      alfa in combination with daily GnRH antagonist can be successfully used in normal
      responder patients stimulated for the first time in an IVF programmeKeywords:
      corifollitropin alfa, GnRH antagonists, ovarian stimulation, pregnancy.

PMID- 29020784
TI  - [Screening of endometrial NK cells in selected infertile patients First part -
      Methods and current results].
AB  - INTRODUCTION: Generaly, natural killer cells (NK cells) are among the most
      important cells of our immune defense system. They are present in the blood,
      decidua but also in secretory endometrium. OBJECTIVE: We investigate an
      association between high density of NK cells CD56+ and NK cells CD16+ into blood
      and secretory endometrium in patients with up to now unexplained recurrent
      miscarriage. At the same time, we focused on diagnosis of antiphospholipid
      syndrome, congenital trombophilic factors, stress factor, and lenght of hormonal
      contraception before conception. DESIGN: Original work-prospective study.
      SETTING: Genetics-Pilsen. METHODS: We investigated 59 patients aged 25-41
      (average 34) years with their history of 3-9 abortions. We monitored their blood
      cells by flow cytometry and endometrium obtained by hysteroscopy performed on the
      22nd-24th day of the menstrual cycle. We concentrated on the cellular immunity
      focused on the identification of lymphocytes CD56+ and CD16+. ELISA method was
      used for identification of antiphospholipid antibodies. RESULTS: Our study goes
      on, we are publishing our preliminary results. We found a high density of
      endometrial NK cells CD56+ in 41/57, NK cells CD16+ in 40/57, both NK cells CD56+
      and CD16+ in 36/57 patients. In 13 women, we identified only sporadically these
      cells in the secretory endometrium. NK cells CD56+ and NK cells CD16+ in the
      blood were all normal number in all our patients. Three of them have a homozygot
      form of Leiden mutation, and 18/57 primary antiphospholipid syndrome, 12 women
      have university education, four of them, medical doctors, have regular night
      services in the hospital. CONCLUSION: Overproduction of endometrial NK cells is
      associated with increased local activity of embryocytotoxic cytokines that may
      negatively affect pregnancy. Treatment of patients with pathological
      immunological findings must be solved individually, as we will show soon in part
      two of our study.

PMID- 29020785
TI  - [How is the Czech oocyte donor? The analysis of their profile].
AB  - OBJECTIVE: The aim of our study was to investigate (a) the basic socio
      demographic characteristics of Czech oocytes donors, (b) their attitudes towards
      anonymous or nonanonymous donation and (c) their motivations to donate oocytes.
      DESIGN: Original article. SETTING: Clinic of Reproductive Medicine and Gynecology
      Zlin. METHODS: A total of 215 oocytes donors participated in this study, which
      was undertaken in years 2015-2016. The data were obtained by an anonymous
      questionnaire. Descriptive and inferential statistics were used to analyzed the
      data. CONCLUSION: The results show that (a) mean age of oocytes donors was 26
      years. Single women (60%) with secondary level education (57%) prevailed. More
      than half of them (55%) had at least one child on their own. About 39% of donors
      were fully employed, 29% women on maternity leave and 16% students. (b) For the
      majority of participants the anonymity is very important. Almost 55% of oocyte
      donors prefer to stay in anonymity and 20% were not sure. In case that anonymity
      would be abolished, only 20% of the Czech oocyte donors would be willing to
      donate. There were no differences based on education (p = 0,358), age (p =
      0,112), marital (p = 0,741) and maternal status (p = 0,691). (c) The main
      motivation to donation was altruism (helping infertile people), no less important
      factors were the finantial motivation and the testing own fertility. The
      altruistic motivation to donate was significantly related to the wish to remain
      anonymous (p = 0,0002). CONCLUSION: The typical Czech oocyte donor is young,
      mainly altruistic woman with her own child who wants to stay in anonymous
      relation to the couple whom she is helping as well as to the possible genetic
      offspring.

PMID- 29020786
TI  - [What is the risk of pelvic organ prolapse recurrence after vaginal hysterectomy
      with colporrhaphy?]
AB  - OBJECTIVE: To determine the risk of prolapse recurrence in patients after vaginal
      hysterectomy with colporrhaphy. DESIGN: Retrospective clinical study. SETTING:
      Department of Obstetrics and Gynaecology, Second Faculty of Medicine, Charles
      University and Motol University Hospital, Prague. METHODS: The trial involved 220
      women who underwent vaginal hysterectomy with anterior and posterior kolporrhaphy
      at our department for uterine prolapse at least grade 2. It was the first vaginal
      surgery in all of the patients. Subjective feeling of pressure in the vagina
      and/or palpable mass in the vagina or in front of the vaginal entrance and/or
      objective finding decline of the vaginal walls or fundus at lest the second
      degree or repeated surgery for prolapse were considered as a prolapse recurrence.
      RESULTS: The mean age at the time of vaginal hysterectomy was 66.7 years (range
      37-88). Only 11 patients were premenopausal (5%), the others were postmenopausal,
      a mean time of posmenopause was 16.9 years. The average parity rate of the study
      group was 2.1. The average duration of the surgery was 68 minutes. Postoperative
      urinary retention was observed in one patient (0.45%). 156 women were enrolled in
      the study. The average length of follow-up was 47 months (minimum 24 months).
      Recurrence of prolapse based on subjective assessment occured in 24 patients
      (15.4 %) with pressure and resistance in the vaginal introitus. According to
      objective criteria, the recurrence of prolapse was diagnosed in 33 (21.2%)
      patients, of which 16 had prolapse of the anterior vaginal wall, three of the
      posterior vaginal wall (two rectocoele, one rectoenterocoele), eight combination
      prolapse of anterior and posterior vaginal wall and vaginal vault prolapse was
      diagnosed in six women. Eight patients (5. 1%) underwent surgery because of
      prolapse recurrence. The mean interval from primary surgery to the time of
      reoperation was 24.4 months (range 6-62). CONCLUSION: Patients have to be
      preoperatively informed about the risk of the prolapse recurrence with the
      recommendation of appropriate preventive arrangements.

PMID- 29020787
TI  - [Carcinosarcoma of the endometrium with melanocytic differentiation, case
      report].
AB  - OBJECTIVE: The case report presents a case of 60-year old woman with a rare
      malignant mixed Mullerian tumor with melanomatous differentiation diagnosed from
      a histology after cervical polyp ablation and curettage. DESIGN: Case report.
      SETTING: Department of gynecology and obstetrics, University Hospital in Pilsen.
      CONCLUSION: Carcinosarcoma, previously malignant mixed Mullerian tumor, is a very
      rare aggressive endometrial carcinoma with low incidence, which typically occurs
      among older women and commonly affects the uterine body and cervix. Clinically,
      the carcinosarcoma is impossible to be distinguished from endometrial carcinoma
      or uterine sarcoma and the definitive diagnosis can only be made based on
      histological examination.

PMID- 29020788
TI  - [Complete molar pregancy with development of non-metastatic persistent
      trophoblastic diseaseA case report, reflection of rules of care and decision
      making processes Forensic responsibility and the position of doctor in the
      general gynecologic and obstetric outpatient practice].
AB  - OBJECTIVE: To define the forensic responsibility and the position of doctor in
      the general gynecologic and obstetric outpatient practice in care of the complete
      molar pregancy. DESIGN: Case report and review article. SETTING: General
      gynecologic and obstetric outpatient practice Velke Mezirici; Sanatorium
      REPROMEDA, Centre of reproductive medicine and preimplantation genetics, Brno;
      Histopatology department of Hospital Jihlava. CASE REPORT: The changing clinical
      presentation of complete molar pregnancy with development of non-metastatic
      gestational trophoblastic disease: management. Subsequent early pregnancies
      outcome following complete hydatiform molar pregnancy. DISCUSSION: Discussed are
      the forensic responsibility and the position of doctor in the general gynecologic
      and obstetric outpatient practice with the collaboration of Trophoblastic Disease
      Center based on the detail expert knowledges: rules of care and decision-making
      processes and potential controversies, the pitfalls of the histopathologic
      diagnosis, the genetics of complete hydatiform mole: new lights on a disease,
      outpatient follow-up and possibility and the risks of the subsequent pregnancy.
      CONCLUSION: The conclusion is trying to guide quickly a doctor in the general
      gynecologic and obstetric outpatient practice in the decision-making processes
      through the crossings of any situation of the complete molar pregnancy and
      outpatient follow-up, alternatively with the collaboration of Trophoblastic
      Disease Center.

PMID- 29020789
TI  - [The role of maternal imunity and woman's microbiome in the pathogenesis of
      preterm labor].
AB  - OBJECTIVE: To summarize available data concerning the role of maternal imunity
      and woman's microbiome in the pathogenesis of preterm labor and their use in
      clinical practice. SETTING: Department of Obstetrics and Gynecology od the First
      Faculty of Medicine, Charles University in Prague, and General Teaching Hospital.
      DESIGN: Review article. METHODS: Compilation od published data from scientific
      literature. CONCLUSION: Preterm labor complicates approximately 10% of all
      pregnancies and represents a serious medical, social and economic problem. In the
      past, a lot of causes of preterm labor were discussed; infection, uteroplacental
      ischemia, decidual hemorrhage, uterine overdistension, cervical disease and
      maternal-fetal tolerance disorder were considered the most common. However,
      chronic inflammation seems to be the common pathogenic process underlying preterm
      labor, irrespective of the original stimulus. Currently, impaired maternal-fetal
      immunological tolerance represents most discussed topic. Growing scientific
      evidence suggests that the immune regulation of the maternal-fetal interface is
      the result of the coordinated interaction among maternal microbiota, trophoblast
      and maternal cellular components. From this view we understand preterm labor as a
      result of disruption of this process.

PMID- 29020790
TI  - [Endometriosis and quality of life].
AB  - OBJECTIVE: This article aims to provide a comprehensive overview of the
      possibilities of evaluating the impact of symptoms of endometriosis on quality of
      life of affected women and to overview the effect of treatment modalities in
      improving of the quality of their life. DESIGN: Review article. SETTING:
      Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles
      University and General University Hospital in Prague. METHODS: Review of results
      of published studies evaluating quality of life in patients with endometriosis.
      CONCLUSION: Symptoms of endometriosis decrease the quality of life of affected
      women, which has significant impact on society. Since the extent of endometriosis
      does not correlate with subjective complaints, it is suitable to evaluate the
      quality of life of patients in addition to assessment of the extent and
      classification of the disease (according to internationally accepted
      classification). The quality of life could be measured and compared by structured
      interviews or by validated questionnaires. Pharmacological as well as surgical
      treatment significantly improve quality of life of patients with endometriosis.
      Routine use of validated questionnaires of quality of life in patients with
      endometriosis might improve the assessment of severity of the disease and
      evaluation of effectiveness of the treatment in the future.

PMID- 29020791
TI  - Parents' and young adults' perspectives on transition outcomes for young adults
      with autism.
AB  - Existing research shows that young adults with autism spectrum disorder have
      poorer outcomes than their peers with other developmental disabilities in the key
      areas of independent living, postsecondary education, and employment. However, we
      understand little about how young adults with autism and their families
      understand and value outcomes and whether these indicators match their goals and
      aspirations. We interviewed parents (n = 21) and young adults with autism
      spectrum disorder (n = 20) about their experiences with the transition to
      adulthood to understand what they consider to be desirable outcomes and how they
      seek to achieve them. Understanding these perspectives will help identify areas
      of need as well as disconnections between service objectives and the goals of
      young adults and their families. Participants described outcomes as more complex
      and nuanced than current conceptions and measures account for. They defined and
      evaluated outcomes in relation to their or their child's individual abilities,
      needs, and desires. These findings provide important insight into challenges to
      and facilitators of desired outcomes, which has implications for programming,
      service delivery, and policy.

PMID- 29020792
TI  - The "Good Old Days" of Courtroom Questioning: Changes in the Format of Child
      Cross-Examination Questions Over 60 Years.
AB  - Recent decades have seen an explosion of research into children's eyewitness
      capabilities and resulted in legal reform to render the adversarial trial process
      more child friendly. Many, however, have been left with the feeling that the most
      intimidating legal process for child complainants-cross-examination-has not
      changed meaningfully despite its potential to distort children's evidence. To
      test this possibility, we compared the cross-examination questioning of
      Australian child sexual abuse complainants in the 1950s to that used in
      contemporary cases. We found that the format of cross-examination questions has
      remained largely consistent over time, with leading questions still making up the
      bulk of the questions asked. The changes that we did observe, however, are
      concerning. Cross-examination questions posed to contemporary child complainants
      were less likely to be open-ended and more likely to be complex, relative to
      those asked in the 1950s. Crucially, contemporary complainants were asked 3 times
      as many cross-examination questions as they were 60 years ago. These changes are
      likely to have detrimental effects on child complainants and their evidence and
      could reduce the ability of jurors to reach just outcomes in these cases.

PMID- 29020793
TI  - Sexual Abuse of Children With Learning Disabilities.
AB  - Although children with a learning disability (LD) are at an increased risk of
      sexual abuse, it is unclear whether conditions specific to their impairment are
      associated with sexual assault or if risk derives from other comorbid conditions
      such as behavioral problems, social skill deficits, or loneliness. Using a
      national probability study of child maltreatment investigations in the United
      States ( n = 2,033), we hypothesized that children over the age of 4 with a LD
      are target congruent to a sexual perpetrator. Seven percent of children were
      identified as having a LD, and the odds of a sexual abuse allegation was 2.5
      times greater for children with a LD relative to children without a LD regardless
      of confounders. Further, type and severity of assaults varied by group: over 3
      times more children with a LD experienced digital or oral copulation compared to
      those without a LD. Results suggest that children with LDs may require tailored
      prevention efforts to protect them from sexual abuse.

PMID- 29020794
TI  - Primary Care Teams and Pharmacist Staffing Ratios: Is There a Magic Number?
AB  - Primary care physician (PCP) shortages are predicted for 2025, and many workforce
      models have recommended the expanded integration of nurse practitioners and
      physician assistants. However, there has been little consideration of
      incorporating clinical pharmacists on primary care teams to address the growing
      number of patient visits that involve medication optimization and management.
      This article summarizes various estimates of pharmacist staffing ratios based on
      number of PCPs, patient panel size, or annual patient encounters. Finally, some
      steps are offered to address the practice- and policy-based implications of
      expanding primary care pharmacist activities at the local and state levels.

PMID- 29020795
TI  - Assay signal as an alternative to titer for assessment of magnitude of an
      antidrug antibody response.
AB  - BACKGROUND: Titer methods are commonly used to characterize the magnitude of an
      antidrug antibody response. Assay S/N is an appealing alternative, but the
      circumstances under which use of signal-to-noise (S/N) is appropriate have not
      been well defined. RESULTS: We validated both titer and S/N-based methods for
      several therapeutics. S/N correlated strongly with titer both in aggregate and
      when examined on a per subject basis. Analysis of impact of antibody magnitude on
      pharmacokinetics yielded the same result using either method. Each assay
      demonstrated excellent precision, good linearity, and adequate drug tolerance.
      CONCLUSION: Under these circumstances, assay S/N is a valid alternative to titer
      for assessment of the magnitude of an antidrug antibody response.

PMID- 29020797
TI  - Extracellular Superoxide Dismutase Attenuates Renal Oxidative Stress Through the
      Activation of Adenosine Monophosphate-Activated Protein Kinase in Diabetic
      Nephropathy.
AB  - AIMS: Oxidative stress plays a crucial role in the pathogenesis of diabetic
      nephropathy (DN). We evaluated whether extracellular superoxide dismutase (EC
      SOD) has a renoprotective effect through activation of adenosine monophosphate
      activated protein kinase (AMPK) in diabetic kidneys. RESULTS: Human recombinant
      EC-SOD (hEC-SOD) was administered to 8-week-old male C57BLKS/J db/db mice through
      intraperitoneal injection once a week for 8 weeks. Renal SOD3 expression was
      suppressed in db/db mice, which was significantly enhanced by hEC-SOD treatment.
      hEC-SOD improved albuminuria, mesangial expansion, and interstitial fibrosis in
      db/db mice. At the molecular level, hEC-SOD increased phosphorylation of AMPK,
      activation of peroxisome proliferative-activated receptor gamma coactivator
      1alpha (PGC-1alpha), and dephosphorylation of forkhead box O transcription factor
      (FoxO)1 and FoxO3a. The protective effects of hEC-SOD were attributed to enhanced
      nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and
      subsequently increased expression of NAD(P)H dehydrogenase 1 and heme oxygenase
      1. Consequently, hEC-SOD recovered from systemic and renal inflammation and
      apoptosis, as reflected by the decreases of serum and renal monocyte
      chemoattractant protein-1 and tumor necrosis factor-alpha levels and increases of
      BCL-2/BAX ratio in diabetic kidney. hEC-SOD also improved oxidative stress and
      resulted in increased renal and urinary 8-hydroxy-2'-deoxyguanosine and 8
      isoprostane levels in db/db mice. In cultured human glomerular endothelial cells,
      hEC-SOD ameliorated apoptosis and oxidative stress caused by high glucose
      exposure through activation of AMPK and PGC-1alpha and dephosphorylation of
      FoxOs. INNOVATION: These findings demonstrated for the first time that EC-SOD can
      potentially ameliorate hyperglycemia-induced oxidative stress, apoptosis, and
      inflammation through activation of AMPK and its downstream pathways in diabetic
      kidneys. CONCLUSIONS: EC-SOD is a potential therapeutic target for treatment of
      type 2 DN through intrarenal AMPK-PGC-1alpha-Nrf2 and AMPK-FoxOs signaling.
      Antioxid. Redox Signal. 28, 1543-1561.

PMID- 29020798
TI  - Serum Bovine Immunoglobulin for Chemotherapy-Induced Gastrointestinal Mucositis.
AB  - Cancer treatments including chemotherapy and radiotherapy treat cancer by
      targeting rapidly dividing cells. Although these forms of treatment damage
      rapidly dividing cancer cells, they are also toxic to the cells of the
      gastrointestinal tract, leading to inflammation of the mucosal layer (mucositis)
      and causing nausea, vomiting, diarrhea, and abdominal pain. Improvement in
      symptoms may allow patients to have better performance status permitting ongoing
      treatment and possibly a better prognosis. This article describes the
      pathophysiology of chemotherapy-induced mucositis and includes 3 case reports of
      treatment of mucositis with serum bovine immunoglobulin.

PMID- 29020796
TI  - Social support, stigma, and HIV disclosure among parents living with HIV in
      Guangxi, China.
AB  - Both stigma and social support have been identified to be associated with HIV
      status disclosure among people living with HIV. This study aimed to examine cross
      sectional associations of perceived social support and multiple types of stigma
      with both disclosure to various target groups and timing of disclosure among
      parents living with HIV (PLHIV) in Guangxi, China. Cross-sectional data from 1254
      PLHIV in Guangxi, China were analyzed. Measures included demographics, disclosure
      to specific groups (steady partner/spouse, children, family and others) and
      timing of disclosure, perceived social support, and three types of HIV-related
      stigma (perceived, internalized, and enacted stigma). Logistic regression
      analyses were performed to identify the associations of interest. The
      participants who reported higher levels of perceived social support were more
      likely to have disclosed to steady partner/spouse, family or others. Those who
      experienced enacted stigma were more likely to have disclosed to children or
      family. Those who were married/cohabitating were more likely to have disclosed to
      steady partner/spouse, and less likely to have disclosed to children, family or
      others. Older PLHIV were less likely to have disclosed to steady partner/spouse,
      or family. Those who had a job were more likely to have disclosed to steady
      partner/spouse. Perceived social support appeared not to be associated with
      timing of disclosure. Those who disclosed within a shorter time after diagnosis
      were more likely to be women or have disclosed to steady partner/spouse, and less
      likely to have higher perceived stigma or have disclosed to family. Interventions
      are needed to help reduce the negative effect of perceived stigma at both family
      and community levels and to help enhance perceived social support in general and
      emotional support in particular among PLHIV, especially males and older adults.

PMID- 29020799
TI  - Is There a Role for 5-HT3 Receptor Antagonists in the Treatment of Opioid-Induced
      Pruritus?
AB  - Pruritus is an unpleasant irritation symptom that can be related to various
      systemic and dermatological conditions. Although underreported, pruritus is a
      common adverse event noted after use of opioid pain medications. This article
      reviews the current understanding of the mechanism of opioid-induced pruritus
      (OIP) and various pharmacological therapies. 5-Hydroxytryptamine 3 (5-HT3)
      receptor antagonists are potentially effective for treating OIP and may be a
      valuable treatment option if further controlled studies are encouraging.

PMID- 29020800
TI  - An Approach to Minimising Risk of Adrenal Insufficiency When Discontinuing Oral
      Glucocorticoids.
AB  - Oral glucocorticoids are commonly used across every field of medicine; however,
      discontinuing them in patients can be challenging. The risk of acute adrenal
      crises secondary to glucocorticoid withdrawal can be fatal and arises from
      chronic suppression of the adrenal glands. Identifying risk factors for adrenal
      suppression in dermatological patients, such as doses greater than 5 to 7.5 mg of
      prednisone equivalent, duration of glucocorticoid use greater than 3 weeks,
      certain medications, and comorbidities, can help risk-stratify patients. The use
      of adrenal gland testing such as basal cortisol levels and adrenocorticotropic
      hormone stimulation tests can confirm adrenal suppression in patients. This
      review article provides an approach that dermatologists can use to minimise the
      risk of adrenal insufficiency in patients discontinuing glucocorticoids and when
      it may be appropriate to use adrenal gland testing.

PMID- 29020801
TI  - Factors Influencing Influenza Vaccination Among Patients With Chronic Obstructive
      Pulmonary Disease: A Population-Based Cross-sectional Study.
AB  - This study aimed to investigate the factors associated with vaccination coverage
      among chronic obstructive pulmonary disease (COPD) patients in Korea using the
      fourth to the sixth Korean National Health and Nutrition Examination Surveys
      (KNHANES IV, V, VI). A total of 16 812 subjects aged 40 years and older who
      underwent spirometry and had an "influenza vaccination history" were analyzed.
      The vaccination rate of middle-aged (40-64 years) COPD patients was only 31.9%;
      whereas, the vaccination rate of elderly (65 years and older) COPD patients was
      80.0%. The results of a multiple regression analysis indicated that older age
      (odds ratio [OR], 1.12; 95% confidence interval [95% CI], 1.09-1.14), poor self
      rated health status (OR, 1.45; 95% CI, 1.14-1.95), regular health check-up (OR,
      2.61; 95% CI, 1.93-3.51), married marital status (OR, 0.64; 95% CI, 0.42-0.96),
      and household income below average (OR, 0.72; 95% CI, 0.53-0.98) were associated
      with influenza vaccination. More attention and targeted interventions are
      required to improve the influenza vaccination rate of COPD patients.

PMID- 29020803
TI  - Pulmonary lymphomatoid granulomatosis diagnosed by image-guided core needle
      biopsy.

PMID- 29020804
TI  - Multi-informant assessment of transition-related skills and skill importance in
      adolescents with autism spectrum disorder.
AB  - Adolescents with autism spectrum disorder have limited participation in the
      transition planning process, despite the link between active participation and an
      improvement in postsecondary education and employment outcomes. The Secondary
      School Success Checklist was designed to support transition planning for
      adolescents with autism spectrum disorder by incorporating their own assessments
      of strengths, skill deficits, and prioritization for instruction along with those
      of their parents and teachers across multiple skill domains. Findings from more
      than 500 adolescents with autism spectrum disorder across the United States
      indicate discrepancies between adolescent, teacher, and parent ratings of skills
      highlighting the importance of the inclusion of multiple perspectives in
      transition planning. Although ratings varied, agreement between adolescents with
      autism spectrum disorder, parents, and teachers across the highest and lowest
      rated skills suggests the need to broaden the focus on critical transition skills
      to include problem-solving, planning for life after high school, and self
      advocacy.

PMID- 29020802
TI  - Recent Advances in the Systems Biology of Aging.
AB  - SIGNIFICANCE: Reductionist studies have contributed greatly to our understanding
      of the basic biology of aging in recent years but we still do not understand
      fundamental mechanisms for many identified drugs and pathways. Use of systems
      approaches will help us move forward in our understanding of aging. Recent
      Advances: Recent work described here has illustrated the power of systems biology
      to inform our understanding of aging through the study of (i) diet restriction,
      (ii) neurodegenerative disease, and (iii) biomarkers of aging. CRITICAL ISSUES:
      Although we do not understand all of the individual genes and pathways that
      affect aging, as we continue to uncover more of them, we have now also begun to
      synthesize existing data using systems-level approaches, often to great effect.
      The three examples noted here all benefit from computational approaches that were
      unknown a few years ago, and from biological insights gleaned from multiple model
      systems, from aging laboratories as well as many other areas of biology. FUTURE
      DIRECTIONS: Many new technologies, such as single-cell sequencing, advances in
      epigenetics beyond the methylome (specifically, assay for transposase-accessible
      chromatin with high throughput sequencing ), and multiomic network studies, will
      increase the reach of systems biologists. This suggests that approaches similar
      to those described here will continue to lead to striking findings, and to
      interventions that may allow us to delay some of the many age-associated diseases
      in humans; perhaps sooner that we expect. Antioxid. Redox Signal. 29, 973-984.

PMID- 29020805
TI  - Intravenous Carbamazepine for Adults With Seizures.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, dosage
      and administration, potential drug-drug interactions, and place in therapy of the
      intravenous (IV) formulation of carbamazepine (Carnexiv) for the treatment of
      seizures in adult patients. DATA SOURCES: A comprehensive PubMed and EBSCOhost
      search (1945 to August 2017) was performed utilizing the keywords carbamazepine,
      Carnexiv, carbamazepine intravenous, IV carbamazepine, seizures, epilepsy, and
      seizure disorder. Additional data were obtained from literature review citations,
      manufacturer's product labeling, and Lundbeck website as well as
      Clinicaltrials.gov and governmental sources. STUDY SELECTION AND DATA EXTRACTION:
      All English-language trials evaluating IV carbamazepine were analyzed for this
      review. DATA SYNTHESIS: IV carbamazepine is FDA approved as temporary replacement
      therapy for treatment of adult seizures. Based on a phase I trial and pooled data
      from 2 open-label bioavailability studies comparing oral with IV dosing, there
      was no noted indication of loss of seizure control in patients switched to short
      term replacement antiepileptic drug therapy with IV carbamazepine. The
      recommended dose of IV carbamazepine is 70% of the patient's oral dose, given
      every 6 hours via 30-minute infusions. The adverse effect profile of IV
      carbamazepine is similar to that of the oral formulation, with the exception of
      added infusion-site reactions. CONCLUSION: IV carbamazepine is a reasonable
      option for adults with generalized tonic-clonic or focal seizures, previously
      stabilized on oral carbamazepine, who are unable to tolerate oral medications for
      up to 7 days. Unknown acquisition cost and lack of availability in the United
      States limit its use currently.

PMID- 29020807
TI  - Recognizing the role of CGRP and CGRP receptors in migraine and its treatment.
AB  - Premise The brain and the sensory nervous system contain a rich supply of
      calcitonin gene-related peptide (CGRP) and CGRP receptor components. Clinical
      studies have demonstrated a correlation between CGRP release and acute migraine
      headache that led to the development of CGRP-specific drugs that either abort
      acute attacks of migraine (gepants) or are effective as prophylaxis (antibodies).
      However, there is still much discussion concerning the site of action of these
      drugs. Problem Here we describe the most recent data related to CGRP in the
      trigeminal ganglion and its connections to the CNS, putative key regions involved
      in migraine pathophysiology. Gepants are small molecules that have limited
      ability to cross the blood-brain barrier (BBB), whereas CGRP antibodies are 1500
      times larger molecules, and are virtually excluded from the brain, with a BBB
      permeability of < 0.1%. Thus we propose that the primary site of action for the
      antimigraine drugs is outside the CNS in areas not limited by the BBB. Potential
      solution Therefore, it is reasonable to discuss the localization of CGRP and its
      receptor components in relation to the BBB. The trigeminovascular system, located
      outside the BBB, has a key role in migraine symptomatology, and it is likely
      targeted by the novel CGRP drugs that successfully terminate migraine headache.

PMID- 29020806
TI  - Transcranial static magnetic field stimulation (tSMS) of the visual cortex
      decreases experimental photophobia.
AB  - Background Transcranial static magnetic field stimulation (tSMS) reduces cortical
      excitability in humans. Methods The objective of this study was to determine
      whether tSMS over the occipital cortex is effective in reducing experimental
      photophobia. In a sham-controlled double-blind crossover study, tSMS (or sham)
      was applied for 10 minutes with a cylindrical magnet on the occiput of 20 healthy
      subjects. We assessed subjective discomfort induced by low-intensity and high
      intensity visual stimuli presented in a dark room before, during and after tSMS
      (or sham). Results Compared to sham, tSMS significantly reduced the discomfort
      induced by high-intensity light stimuli. Conclusions The visual cortex may
      contribute to visual discomfort in experimental photophobia, providing a
      rationale for investigating tSMS as a possible treatment for photophobia in
      migraine.

PMID- 29020809
TI  - Fibromyalgia as a Predictor of Complex Regional Pain Syndrome After Distal Radius
      Fracture.
AB  - BACKGROUND: Complex regional pain syndrome (CRPS) can be a devastating
      complication following extremity injury, but risk factors are not well
      understood. The purpose of this study was to investigate the association between
      fibromyalgia and the development of CRPS after distal radius fracture. METHODS:
      The PearlDiver Medicare database was queried using International Classification
      of Diseases, 9th Revision (ICD-9) and Current Procedural Terminology (CPT) codes
      for diagnoses and treatments of distal radius fractures. Patients were separated
      into fibromyalgia and control cohorts, and the prevalence of CRPS was measured at
      3, 6, 9, and 12 months from the date of injury or procedure. Demographic factors,
      treatment modality, and comorbid conditions were analyzed by multivariable
      logistic regression to reduce confounding and identify additional risk factors.
      RESULTS: Database queries yielded 853 186 patients diagnosed or treated for
      distal radius fracture, with 6% having previous diagnosis of fibromyalgia. The
      prevalence of CRPS following distal radius fracture was increased at 3, 6, 9, and
      12 months in the fibromyalgia cohort compared with the control c, with a 1-year
      incidence of 0.51% compared with 0.20% (odds ratio [OR], 2.54, P < .001).
      Multivariable logistic regression supported the association, with estimated OR of
      2.0 ( P < .001). In addition, female gender, surgical or manipulative treatment,
      and anxiety were positively associated with CRPS, and age >65, diabetes, and
      heart failure were negatively associated. CONCLUSIONS: While the basis of the
      association between fibromyalgia and CRPS is unknown, our data suggest that it
      could serve as a useful predictor of CRPS risk, promoting increased vigilance for
      CRPS symptoms and earlier recognition and treatment, thereby improving patient
      outcomes.

PMID- 29020808
TI  - Acute hemophilic hemarthrosis: is local cryotherapy recommended?
AB  - INTRODUCTION: The management of acute hemophilic hemarthrosis (AHH) classically
      has consisted of factor replacement therapy and RICE (rest, ice, compression and
      elevation). However, there is still a controversy in the literature regarding the
      role of local cryotherapy (LC) in AHH. Areas covered: The aim of this article is
      to review the potential role of LC in AHH. Expert commentary: Some authors have
      reported that LC attenuates joint inflammation and has a positive influence on
      controlling articular swelling and temperature. However, other authors have
      stated that low temperature is associated with impairment of coagulation enzyme
      activity and platelet function. Although some reports have mentioned the benefits
      of LC in AHH and other have mentioned its adverse events, the data on the topic
      are still scant and preliminary. Literature of LC in the management of AHH is
      controversial. Whilst LC has always been considered as an unquestionable
      necessity in the management of AHH, it should be utilized with caution until a
      randomized study can solve the dilemma.

PMID- 29020810
TI  - Effect of high-hydrostatic pressure and moderate-intensity pulsed electric field
      on plum.
AB  - Moderate intensity pulse electric fields were applied in plum with the aim to
      increase bioactive compounds content of the fruit, while high-hydrostatic
      pressure was applied to preserve the purees. High-hydrostatic pressure treatment
      was compared with an equivalent thermal treatment. The addition of ascorbic acid
      during puree manufacture was also evaluated. The main objective of this study was
      to assess the effects on microorganisms, polyphenoloxidase, color and bioactive
      compounds of high-hydrostatic pressure, or thermal-processed plum purees made of
      moderate intensity pulse electric field-treated or no-moderate intensity pulse
      electric field-treated plums, after processing during storage. The application of
      moderate intensity pulse electric field to plums slightly increased the levels of
      anthocyanins and the antioxidant activity of purees. The application of
      Hydrostatic-high pressure (HHP) increased the levels of bioactive compounds in
      purees, while the thermal treatment preserved better the color during storage.
      The addition of ascorbic acid during the manufacture of plum puree was an
      important factor for the final quality of purees. The color and the bioactive
      compounds content were better preserved in purees with ascorbic acid. The no
      inactivation of polyphenoloxidase enzyme with treatments applied in this study
      affected the stability purees. Probably more intense treatments conditions (high
      hydrostatic pressure and thermal treatment) would be necessary to reach better
      quality and shelf life during storage.

PMID- 29020812
TI  - Prospective longitudinal assessment of the fetal left modified Myocardial
      Performance Index.
AB  - INTRODUCTION: The fetal left modified Myocardial Performance Index (Mod
      myocardial performance index (MPI)) is a measure of systolic versus diastolic
      time intervals obtained from a single cardiac cycle with ultrasound. It is a
      measure of global ventricular function and has been investigated for potential
      utility in fetal conditions associated with cardiac dysfunction. OBJECTIVES: The
      objective of this study is to compare values from a precisely replicated fetal
      left Mod-MPI technique to published reference ranges. METHODS: Three hundred and
      sixty-five nulliparae prospectively underwent fetal left Mod-MPI measurement at
      27+0-29+0 and 35+0-37+0 weeks' gestation. Measurements from pregnancies
      complicated by gestational diabetes mellitus, preeclampsia, or a small-for
      gestational-age (<10th centile) infant were excluded. Mod-MPI values were
      compared with three published references created using similar measurement
      techniques. RESULTS: Compared with one selected reference, at 29+0 and 35+0-37+0
      weeks' gestation, 90-100% of our values fell within the 5th-95th percentile range
      as expected. Thus, this reference range was validated for our population in late
      pregnancy. However, the expected level of concordance was not seen at 27+0-28+6
      weeks'. The other two references to which we compared our Mod-MPI values
      demonstrated poor concordance, especially at 27+0-29+0 weeks'. Pearson
      interobserver correlation was also improved at 35+0-37+0 weeks' at 0.434,
      compared with 0.083 at 27+0-29+0 weeks' gestation. CONCLUSIONS: Concordance and
      interobserver variability between our cohort and similar populations were both
      improved at 35+0-37+0 weeks' compared with 27+0-29+0 weeks' gestation. Overall,
      variable Mod-MPI reproducibility across gestations limits clinical application,
      especially earlier in pregnancy. Manual Mod-MPI measurement should be considered
      most reliable in late pregnancy until automated MPI measurement is possible.

PMID- 29020811
TI  - Delaying microbial proliferation in freshly peeled shallots by active packaging
      incorporating ethanol vapour-controlled release sachets and low storage
      temperature.
AB  - This research was conducted to investigate effects of ethanol vapour released in
      active packaging and storage temperatures on the quality of freshly peeled
      shallots. The package tested was a solid polypropylene tray incorporating an
      ethanol vapour-controlled release sachet. The sachet was made of an aluminium
      foil film on one side and either low-density polyethylene or nylon/polyethylene
      on the other. Individual sachets contained silica gel adsorbent as the carrier
      pre-loaded with ethanol. One sachet was placed in each tray containing the peeled
      shallots and the tray was heat sealed with the low-density polyethylene film lid.
      Packages were stored at either 10 or 25 C for 10 d. Trays containing only peeled
      shallots were designated as controls. High storage temperature stimulated quality
      changes in the shallots. Although ethanol vapour accumulated in the active
      package headspace, the extent to which ethanol concentrations increased within
      the shallots was not significantly different from that in the control packages.
      Microbial proliferation in terms of yeast and mould counts could be delayed
      through a combination of 10 C and ethanol vapour released from the low-density
      polyethylene sachet. The ethanol vapour accumulated in the packages did not have
      a significant effect on mass loss, firmness, and colour changes in the peeled
      shallots, or on the concentrations of oxygen and carbon dioxide in the packages.

PMID- 29020813
TI  - Early neonatal hypoglycemia: incidence of and risk factors. A cohort study using
      universal point of care screening.
AB  - OBJECTIVE: The objective of this study is to determine the true incidence of
      early neonatal hypoglycemia and to confirm potential risk factors. STUDY DESIGN:
      The study was conducted at tertiary Medical Center in Israel, between June and
      September 2014. First blood glucose concentrations of all infants admitted to the
      nursery were measured using a "point of care" analyzer (Accu-Chek). We recorded
      risk factors for hypoglycemia such as birth weight, gestational age, maternal
      diabetes and demographics and analyzed their association with two hypoglycemia
      cutoffs: 40 and 47 mg/dl. RESULTS: Of 4000 newborns admitted during that period,
      3595 were analyzed after excluding 405 who had missing data. Glucose level was
      obtained at a mean age of 74 +/- 30 min. One hundred and twenty-four newborns
      (3.4%) had blood glucose levels below 40 mg/dl and 435 (12.1%) below 47 mg/dl.
      Univariate analyses revealed that gestational age, maternal diabetes, low birth
      weight (<2500 g), and twin delivery were associated with early neonatal
      hypoglycemia. Other risk factors (e.g. large or small for gestational age, birth
      weight >3800 g) were not. In multivariate analysis, gestational age remained the
      strongest association, while maternal diabetes and low birth weight became non
      significant. CONCLUSIONS: We showed a high occurrence of early hypoglycemia in
      normal newborns using universal screening. The strongest risk factor was early
      gestational age. Surprisingly, incidence of early hypoglycemia in the presence of
      other classical risk factors was like that of the general population.

PMID- 29020815
TI  - 'Bony' cubital tunnel syndrome caused by heterotopic ossification.
AB  - We reported a rare case of cubital tunnel syndrome caused by heterotopic
      ossification after burns. The ulnar nerve was encircled by bony tunnel structure
      which cause nerve compression, resulting in ulnar nerve lesion. Our case sheds
      light on possible etiological association which may help clinical management.

PMID- 29020814
TI  - The Effect of Socioeconomic Factors on Outcomes of Distal Radius Fractures: A
      Systematic Review.
AB  - BACKGROUND: Socioeconomic factors are known to affect outcomes for both medical
      and surgical conditions. The purpose of this systematic review was to assess the
      current evidence regarding the effect of socioeconomic factors such as income,
      geographic location, educational level, and occupation on clinical outcomes after
      distal radius fractures. METHODS: A systematic search strategy was performed to
      identify studies commenting on the effect of socioeconomic factors on clinical
      outcomes following open or closed distal radius fracture repair. Abstract and
      full-text screening was performed by 2 independent reviewers, and articles were
      evaluated by Structured Effectiveness Quality Evaluation Scale (SEQES). Treatment
      outcomes of interest included, but were not limited to, pain, function, range of
      motion, and grip strength. RESULTS: There were 1745 studies that met our
      inclusion and exclusion criteria for abstract screening. Of these, 48 studies met
      our inclusion criteria for full-text screening and 20 studies met our criteria
      for quality analysis with the SEQES score. There were 3 studies of high quality,
      16 of moderate quality, and 1 of low quality. Meta-analyses were not possible due
      to the variability in outcomes of interest across papers. CONCLUSIONS: Patient
      factors indicative of socioeconomic status are relevant predictors of functional
      outcome after distal radius fractures. There is currently limited evidence in
      this area of research, and further examination should be considered to improve
      outcomes from a patient and system standpoint.

PMID- 29020816
TI  - Predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy
      with dichorionic diamniotic twin pregnancies.
AB  - OBJECTIVE: The aim of our study was to investigate the predictors of adverse
      perinatal outcomes in intrahepatic cholestasis of pregnancy (ICP) with
      dichorionic diamniotic (DCDA) twin pregnancies. METHODS: This study was a
      retrospective study of women diagnosed with ICP and DCDA twin pregnancies in
      Chengdu's women and children's central hospital. These patients were subdivided
      into mild and severe ICP groups according to total bile acid (TBA) level. The
      clinical characteristics and perinatal outcomes were collected and compared
      between the two groups. Logistic regression analysis was developed to evaluate
      predictors of adverse perinatal outcomes. RESULTS: About 134 cases were included
      in the study. Eighty-four cases were in the mild ICP group, and the other 50
      cases were in the severe ICP group. Level of alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin
      (TBIL), and direct bilirubin (DBIL) in the severe ICP group were significant
      higher than those in the mild ICP group. The rate of delivery before 34
      gestational weeks, meconium-stained amniotic fluid, and composite adverse
      neonatal outcome were higher in the severe ICP group than those in the mild ICP
      group. After adjusting for confounders, ICP onset gestational age (GA) <30 weeks
      and AST >200U/l were associated with GA at delivery <34 weeks. ALP >400U/l was an
      independent risk factor of meconium-stained amniotic fluid. ICP onset GA <30
      weeks was an independent risk factor of composite adverse neonatal outcome.
      CONCLUSION: ICP onset GA <30 weeks, TBA >40 umol/l, AST >200U/l, and ALP >400U/l
      were associated with composite adverse perinatal outcomes in ICP with DCDA twin
      pregnancies. For those patients with these characteristics, fetal surveillance
      and treatment should be enhanced.

PMID- 29020817
TI  - Use of the Social Problem Solving Inventory-Revised With Forensic Populations: A
      Psychometric Critique.
AB  - The Social Problem Solving Inventory-Revised (SPSI-R) is a popular psychometric
      tool used with multiple populations to assess individual problem solving ability.
      Problem solving deficits have been implicated within forensic literature, and
      therefore, assessment of these skills is essential to aid decision making and
      appraisal of treatment change in forensic populations. This review discusses the
      extent of the validity and reliability of the SPSI-R within forensic populations,
      and concludes that while the tool has some valid psychometric properties, further
      studies using larger forensic samples and being inclusive of more subgroups in
      forensic contexts are needed to provide reliable group comparison norms. Overall,
      users of the SPSI-R should be aware of the strengths and limitations of using
      this tool with a forensic population. Impression management is also a
      consideration when using the SPSI-R within forensic settings.

PMID- 29020818
TI  - Can We Hasten Development? Effects of Treatment on Psychosocial Maturity.
AB  - Research continues to highlight factors associated with developmental immaturity,
      including persistent delinquency. This article examines whether aspects of
      developmental immaturity, psychosocial maturity, and emotion regulation are
      responsive to therapeutic intervention. Fifty-seven female youth in secure
      residential juvenile justice facilities participated in a randomized controlled
      trial of the Juvenile Justice Anger Management (JJAM) Treatment for Girls, an
      intervention that targets skills relevant to psychosocial maturity, including
      problem-solving, coping, and emotion regulation. Participants in JJAM showed
      increases in temperance, providing evidence that intervention might stimulate
      psychosocial development. Implications for treatment, evaluation, and measurement
      of psychosocial maturity are discussed.

PMID- 29020819
TI  - Update on relapsed ovarian cancer treatment: from new consensus to daily clinical
      practice.
AB  - The outcome of the 5th Ovarian Cancer Consensus Conference (OCCC) held in
      November 2015 in Tokyo, Japan, was the development of new and revised consensus
      statements to guide clinical investigations in ovarian cancer. The OCCC
      statements may also have direct application to daily clinical practice. This
      review examines the consensus statements for recurrent ovarian cancer and their
      impact on treatment paradigms. Importantly, patients are no longer to be
      categorized by the platinum-free interval (with its arbitrary 6-month cut-off
      points) but according to the question: 'is platinum still an option for the
      patient?' Another important change since the 4th OCCC in 2010 is the inclusion of
      BRCA mutation status when defining patient subgroups for entry into clinical
      trials.

PMID- 29020820
TI  - Managing relapsed ovarian cancer in a rapidly evolving landscape.

PMID- 29020821
TI  - When nonplatinum is the answer: the role of trabectedin plus pegylated liposomal
      doxorubicin in recurrent ovarian cancer.
AB  - Trabectedin + pegylated liposomal doxorubicin (PLD) offers a well tolerated and
      effective nonplatinum, nontaxane alternative for treatment of ovarian cancer
      patients with a treatment-free interval after platinum beyond 6 months,
      especially for those relapsing between 6 and 12 months and those who are not
      candidates to receive platinum-based therapy. Using the nonplatinum trabectedin +
      PLD combination gives patients time to recover from platinum-related toxicities
      and may restore platinum sensitivity in tumor cells. The sequence effect, by
      which intercalation of trabectedin + PLD between platinum regimens may enhance
      the activity of next platinum and improve survival, is currently under
      investigation in the Phase III prospective INternational OVArian cancer patients
      Trial with YONdelis.

PMID- 29020822
TI  - Trabectedin mechanism of action and platinum resistance: molecular rationale.
AB  - Trabectedin presents a complex mode of action affecting key cell biology
      processes in tumor cells and in the tumor microenvironment. In ovarian cancer
      patients with a platinum treatment-free interval of 6-12 months treated with
      trabectedin + pegylated liposomal doxorubicin (PLD) or single-agent PLD, and
      retreated with platinum after relapse, overall survival was significantly
      prolonged in the trabectedin + PLD group. Mechanisms by which trabectedin
      restores tumor sensitivity to platinum include its interaction with components of
      the nucleotide excision repair machinery in tumor cells and inhibition of
      inflammatory mediators such as IL-6 in the tumor microenvironment. Additionally,
      BRCA mutations and associated homologous recombination repair deficiency may
      contribute to enhanced sensitivity to trabectedin observed in BRCA-mutated
      patients with ovarian cancer.

PMID- 29020823
TI  - Platinum or nonplatinum in recurrent ovarian cancer: that is the question.
AB  - Although platinum-based chemotherapy continues to be the first-line option for
      advanced ovarian cancer and for platinum recurrences beyond 6 months, platinum
      rechallenge is not the best approach for some patients, such as those with
      residual toxicities, platinum-related hypersensitivity reactions or limited
      platinum-sensitivity (i.e., a platinum treatment-free interval [TFIp] of 6-12
      months). Results of the MITO-8 study called into question the role of single
      agent nonplatinum-based regimens in this specific subset of ovarian cancer
      patients. The current article summarizes the results of the MITO-8 study
      highlighting key limitations, and discusses the role of the nonplatinum-based
      combination of trabectedin + pegylated liposomal doxorubicin in the management of
      ovarian cancer patients who relapse between 6 and 12 months after last platinum.

PMID- 29020824
TI  - Biomarkers of oxidative stress and protein-protein interaction in chronic
      obstructive pulmonary disease.
AB  - CONTENT: The increased oxidative stress in chronic obstructive pulmonary disease
      (COPD) patients is the result of increased inhaled oxidants, generated by various
      cells of the airways. OBJECTIVE: The investigation included measurements of
      malondiadehyde (MDA), uric acid, ascorbic acid, and matrix metalloproteinase-12
      (MMP-12) in COPD patient. We also performed genetic analysis for protein-protein
      interaction (PPI) network. MATERIALS AND METHODS: The study was conducted on
      healthy subjects with normal lung function (NS, 14 subjects) and 28 patients
      (Global Initiative for Chronic Obstructive Lung Disease (Gold) 1 and Gold 2) with
      COPD. RESULTS: There was significant (p < .001) increase in MMP-12, MDA and uric
      acid levels as compared to healthy controls. A significant (p < .001) decline in
      ascorbic acid level was observed in COPD patients. The PPI was found to be 0.833
      which indicated that proteins present in COPD are linked. DISCUSSION AND
      CONCLUSION: This study suggests oxidative stress plays an important role in COPD
      and the PPI provide indication that proteins present in COPD are linked.

PMID- 29020825
TI  - The yield of the prenatal work-up in intrauterine growth restriction and the
      spectrum of fetal abnormalities detected postnatally ?.
AB  - OBJECTIVE: To evaluate the yield of work-up in intrauterine growth restriction
      (IUGR) pregnancies and their outcomes. MATERIALS AND METHODS: Retrospective data
      regarding prenatal work-up (serology, genetic testing and imaging), and neonatal
      outcomes of 198 IUGR pregnancies (estimated fetal weight <10th percentile) were
      analyzed. RESULTS: IUGR was isolated in 72 cases. Work-up performed in 158 (80%)
      cases was positive in 4 (2.5%). No abnormalities were detected in prenatal
      genetic testing. Echocardiogram performed in 27 cases was abnormal in 3 (11.1%).
      Serological testing performed in 150 pregnancies (75.8%) detected 1 case (0.7%)
      of cytomegalovirus (CMV) infection. Thirteen neonates (6.5%) were diagnosed with
      significant health problems. A positive work-up and significant postnatal health
      problems were not correlated with IUGR severity, symmetry or additional
      concurrent findings. CONCLUSION: The yield of IUGR work-up is not clear and is
      probably highest for fetal echocardiography. The rate of significant adverse
      outcomes after birth is increased in IUGR pregnancies.

PMID- 29020826
TI  - Redefining Zone II: Anatomy of the Flexor Digitorum Superficialis Insertion.
AB  - BACKGROUND: Flexor zone II is defined as the region spanning the proximal aspect
      of the A1 pulley to the insertion of the flexor digitorum superficialis (FDS)
      tendon. Descriptions of the FDS insertion are inconsistent in the literature, but
      zones of injury are frequently determined with reference to superficial
      landmarks. The purpose of this study was to describe the footprint of the FDS
      insertion and define its relationship to the proximal interphalangeal (PIP) skin
      crease. METHODS: The FDS insertion on the index, middle, ring, and small fingers
      was dissected in 6 matched pairs of fresh-frozen cadaveric hands. A Kirschner
      wire was used to mark the level of the PIP skin crease on bone before
      measurements of the FDS footprint and its position relative to the PIP skin
      crease were made using digital calipers. RESULTS: The radial and ulnar FDS slips
      inserted a mean distance of 3.22 mm from the distal aspect of the PIP skin crease
      and varied by digit. The mean distal extent of the FDS insertion was 8.29 mm. The
      mean length of the insertion of each FDS slip was 5.15 mm and the mean width was
      1.9 mm. CONCLUSIONS: The radial and ulnar FDS slips insert on average 3.22 mm
      distal to the PIP skin crease and vary by digit. Knowledge of the FDS insertion
      is clinically relevant when differentiating between flexor zone I and zone II
      injuries, planning surgical approaches to the finger, and in guiding patient
      expectations for surgery given the variability in outcome based on zone of
      injury.

PMID- 29020828
TI  - Timing of antibiotic prophylaxis in cesarean section: retrospective, difference
      in-differences estimation of the effect on surgical-site-infection.
AB  - BACKGROUND: Cesarean section (CS) is one of the most common surgical procedures
      performed worldwide. Surgical-site-infection (SSI) occurs in approximately 5-10%
      of CS. The benefit of prophylactic antibiotics for prevention of SSI has been
      demonstrated in the literature. The optimal timing of antibiotic prophylaxis
      (prior to surgical incision versus after cord clamping) was investigated in
      recent studies. In January 2014, the Israeli Ministry of Health introduced a
      national quality measure which monitors the administration of prophylactic
      antibiotics in CS. The custom clinical practice in our medical center was to
      administer prophylactic antibiotics immediately after cord clamping. Upon
      introduction of the national quality measurement program, the practice was
      changed to administration of antibiotics prior to surgical incision. Our
      objective was to examine the effect of timing of prophylactic antibiotics
      administration on the incidence of SSI following CS, in a single medical center
      that performs a large volume of deliveries, with a low rate of CS. MATERIAL AND
      METHODS: Taking advantage of a discrete change in clinical practice, we used
      retrospective data and applied difference-in-differences design to estimate the
      effect of the timing of prophylactic antibiotics administration on SSI rates. The
      analysis included all CSs performed during 2012-2015 and all hysterectomies
      conducted during the study period. RESULTS: The coverage rates of prophylactic
      antibiotics in CS before and after the policy change were 99.10% and 99.03%,
      respectively. The rates of SSI following CS, before and after the policy change,
      were 2.63% (n = 2499) and 2.32% (n = 3840), respectively. The rates of SSI
      following hysterectomy, before and after the policy, change were 6.82% (n = 396)
      and 7.09% (n = 437), respectively. Difference-in-differences (DID) estimates of
      the effect of policy change on the incidence of SSI in linear and logistic
      regression models were not significant (B = -0.6%, p = .64; odds ratio = 0.84, p
      = .58, respectively). CONCLUSIONS: We found no effect of the timing of
      prophylactic antibiotic administration (prior to surgical incision versus after
      cord clamping) on SSI rates following CS.

PMID- 29020829
TI  - Preferences in Sleep Position Correlate With Nighttime Paresthesias in Healthy
      People Without Carpal Tunnel Syndrome.
AB  - BACKGROUND: Carpal tunnel syndrome has been associated with sleep position
      preferences. The aim of this study is to assess self-reported nocturnal
      paresthesias and sleeping position in participants with and without carpal tunnel
      syndrome diagnosis to further clinical knowledge for preventive and therapeutic
      interventions. METHODS: A cross-sectional survey study of 396 participants was
      performed in young adults, healthy volunteers, and a patient population.
      Participants were surveyed on risk factors for carpal tunnel syndrome, nocturnal
      paresthesias, and sleep preferences. Binary logistic regression analysis was
      performed comparing participants with rare and frequent nocturnal paresthesias.
      Subanalyses for participants without carpal tunnel syndrome under and over 21
      years of age were performed on all factors significantly associated with
      subclinical compression neuropathy in the overall population. RESULTS: Thirty
      three percent of the study population experienced nocturnal paresthesias at least
      weekly. Increased body mass index ( P < .001) and sleeping with the wrist flexed
      ( P = .030) were associated with a higher frequency of nocturnal paresthesias.
      Side sleeping was associated with less frequent nocturnal symptoms ( P = .003).
      In participants without carpal tunnel syndrome, subgroup analysis illustrated a
      relationship between nocturnal paresthesias and wrist position. In participants
      with carpal tunnel syndrome, sleeping on the side had a significantly reduced
      frequency of nocturnal paresthesias. CONCLUSION: This study illustrates nocturnal
      paresthesias in people without history of carpal tunnel syndrome including people
      younger than previously reported. In healthy patients with upper extremity
      subclinical compression neuropathy, sleep position modification may be a useful
      intervention to reduce the frequency of nocturnal symptoms prior to developing
      carpal tunnel syndrome.

PMID- 29020830
TI  - A novel biomarker explaining the role of oxidative stress in exercise and l
      tyrosine supplementation: thiol/disulphide homeostasis.
AB  - The present study aimed to evaluate the relationship between exercise and both l
      tyrosine and oxidative stress using thiol/disulphide homeostasis via a novel
      biomarker in rats. Following the completion of the exercise and l-tyrosine
      protocol, serum total thiol, native thiol, and disulphide concentrations were
      determined using a novel automated measurement method. Compared with the control
      group, serum dynamic disulphide levels were significantly lower in the E group
      (116.75 +/- 10.49; p < .05) and the highest in the LT group (151.0 +/- 5.84). The
      lowest oxidised thiol (49.75 +/- 6.18; p = .087) and the highest reduced thiol
      (75.38 +/- 3.16; p = .079) rates were determined to be in the E group. The
      highest oxidised thiol value was observed in the LT group. Exercise positively
      affects thiol/disulphide homeostasis, which is a novel indicator of oxidant
      antioxidant parameters. Additionally, l-tyrosine appears to be more convenient
      combined with exercise. The new method used in our study proposes a promising,
      practical, and useful method for assessing the oxidative stress parameters.

PMID- 29020832
TI  - Cultural Adaptation and Psychometric Properties of the Shirom-Melamed Vigor
      Measure (SMVM) With Workers in Spain.
AB  - Shirom's proposal about engagement focuses on vigor. Under this approach, vigor
      is considered an affect that mediates the relationship between resources,
      behaviors, and attitudes related to psychological functioning and health. It is
      important for occupational health professionals to have adequate measures of this
      construct. The Shirom-Melamed vigor measure (SMVM) was developed to capture this
      sense of energy comprising three components (physical strength, emotional energy,
      and cognitive liveliness). In the absence of a Spanish version of the SMVM, our
      aim is to perform a cultural adaptation and to further analyze its psychometric
      properties. In Study 1, we culturally adapt the SMVM in Spanish samples. It
      incorporates a careful development of a three-step procedure according to the
      International Test Commission and qualitative analyses to ensure a consensus
      version. Twenty-six individuals were involved. In Study 2, the responses of 203
      workers from different organizations show the validity and reliability of the
      instrument. Confirmatory factor analyses yield a model with three interrelated
      dimensions showing good fit indices. Furthermore, concurrent validity is
      demonstrated. Finally, we discuss the usefulness of the SMVM for occupational
      health professionals.

PMID- 29020827
TI  - The frequency and clinical significance of intra-amniotic inflammation in twin
      pregnancies with preterm labor and intact membranes.
AB  - OBJECTIVE: The objective of this study is to evaluate the frequency and clinical
      significance of intra-amniotic inflammation in twin pregnancies with preterm
      labor and intact membranes. STUDY DESIGN: Amniotic fluid (AF) was retrieved from
      both sacs in 90 twin gestations with preterm labor and intact membranes
      (gestational age between 20 and 34 6/7 weeks). Preterm labor was defined as the
      presence of painful regular uterine contractions, with a frequency of at least 2
      every 10 min, requiring hospitalization. Fluid was cultured and assayed for
      matrix metalloproteinase-8. Intra-amniotic inflammation was defined as an AF
      matrix metalloproteinase-8 concentration >23 ng/mL. RESULTS: The prevalence of
      intra-amniotic inflammation for at least 1 amniotic sac was 39% (35/90), while
      that of proven intra-amniotic infection for at least one amniotic sac was 10%
      (9/90). Intra-amniotic inflammation without proven microbial invasion of the
      amniotic cavity was found in 29% (26/90) of the cases. Intra-amniotic
      inflammation was present in both amniotic sacs for 22 cases, in the presenting
      amniotic sac for 12 cases, and in the non-presenting amniotic sac for one case.
      Women with intra-amniotic inflammation observed in at least one amniotic sac and
      a negative AF culture for microorganisms had a significantly higher rate of
      adverse pregnancy outcome than those with a negative AF culture and without intra
      amniotic inflammation (lower gestational age at birth, shorter amniocentesis-to
      delivery interval, and significant neonatal morbidity). Importantly, there was no
      significant difference in pregnancy outcome between women with intra-amniotic
      inflammation and a negative AF culture and those with a positive AF culture.
      CONCLUSION: Intra-amniotic inflammation is present in 39% of twin pregnancies
      with preterm labor and intact membranes and is a risk factor for impending
      preterm delivery and adverse outcome, regardless of the presence or absence of
      bacteria detected using cultivation techniques.

PMID- 29020831
TI  - Evaluation of the Role of Laparoendoscopic Single-Site Surgery vs Minilaparoscopy
      for Treatment of Upper Urinary Tract Pathologies: Prospective Randomized
      Comparative Study.
AB  - OBJECTIVES: To present the first prospective randomized comparison between
      laparoendoscopic single-site surgery (LESS) and minilaparoscopy (ML) for
      treatment of upper urinary tract pathologies. PATIENTS AND METHODS: Between
      January 2013 and June 2015, patients with different upper urinary pathologies
      were blindly randomized to both LESS and ML. All procedures were done by single
      experienced surgeon. Both cohorts were compared regarding demographic data, peri
      and postoperative characteristics, and visual analog pain scale (VAS). Cosmetic
      outcome was assessed after 12 months using patient scar assessment scale (PSAS)
      and observer scar assessment scale (OSAS). RESULTS: Sixty patients were
      randomized into two equal groups with comparable demographic and preoperative
      characteristics. Indications included nephrectomy, pyeloplasty, cyst
      marsupialization, adrenalectomy, and repair of retrocaval ureter. Operative time
      was 167 +/- 24 and 145 +/- 39 minutes in LESS and ML groups, respectively (p =
      0.09). Estimated blood loss was 59 +/- 34 and 43 +/- 42 mL in both groups,
      respectively (p = 0.2). VAS was 1.7 +/- 0.6 and 2.8 +/- 0.5 in both groups,
      respectively (p = 0.02). PSAS and OSAS were 5.9 +/- 0.85 and 10.6 +/- 1.98 vs 8.9
      +/- 0.9 and 13.5 +/- 6.3 in both groups, respectively (p > 0.05). There were no
      intraoperative complications, conversions to open surgery, or conventional
      laparoscopy in both groups. Mean postoperative Diclofenac Na was 151.7 +/- 35.6
      and 169.7 +/- 47.3 mg in both groups, respectively (p = 0.04). Postoperative
      complications rate and hospital stay were comparable between both groups.
      CONCLUSION: Both LESS and ML have comparable operative time, blood loss,
      complication rate, and hospital stay in treatment of upper urinary tract
      pathologies. However, LESS is associated with less analgesic requirement and
      better cosmetic outcome.

PMID- 29020833
TI  - Using Generalizability Theory to Inform Optimal Design for a Nursing Performance
      Assessment.
AB  - The promotion of competency of nurses and other health-care professionals is a
      goal shared by many stakeholders. In nursing, observation-based assessments are
      often better suited than paper-and-pencil tests for assessing many clinical
      abilities. Unfortunately, few instruments for simulation-based assessment of
      competency have been published that have undergone stringent reliability and
      validity evaluation. Reliability analyses typically involve some measure of rater
      agreement, but other sources of measurement error that affect reliability should
      also be considered. The purpose of this study is three-fold. First, using extant
      data collected from 18 nurses evaluated on 3 Scenarios by 3 Raters, we utilize
      generalizability (G) theory to examine the psychometric characteristics of the
      Nursing Performance Profile, a simulation-based instrument for assessing nursing
      competency. Results corroborated findings of previous studies of simulation-based
      assessments showing that obtaining desired score reliability requires
      substantially greater numbers of scenarios and/or raters. Second, we provide an
      illustrative exemplar of how G theory can be used to understand the relative
      magnitudes of sources of error variance-such as scenarios, raters, and items-and
      their interactions. Finally, we offer general recommendations for the design and
      psychometric study of simulation-based assessments in health-care contexts.

PMID- 29020834
TI  - High transverse skin incisions may reduce wound complications in obese women
      having cesarean sections: a pilot study.
AB  - OBJECTIVE: Women having cesarean section have a high risk of wound complications.
      Our objective was to determine whether high transverse skin incisions are
      associated with a reduced risk of cesarean wound complications in women with BMI
      greater than 40. METHODS: A retrospective cohort study was undertaken of
      parturients ages 18-45 with BMI greater than 40 having high transverse skin
      incisions from January 2010 to April 2015 at a tertiary maternity hospital.
      Temporally matched controls had low transverse skin incisions along with a BMI
      greater than 40. The primary outcome, wound complication, was defined as any
      seroma, hematoma, dehiscence, or infection requiring opening and
      evacuating/debriding the wound. Secondary outcomes included rates of
      endometritis, number of hospital days, NICU admission, Apgar scores, birth
      weight, and gestational age at delivery. Analysis of outcomes was performed using
      two-sample t-test or Wilcoxon rank-sum test for continuous variables and Fisher's
      exact test for categorical variables. RESULTS: Thirty-two women had high
      transverse incisions and were temporally matched with 96 controls (low transverse
      incisions). The mean BMI was 49 for both groups. There was a trend toward reduced
      wound complications in those having high transverse skin incisions, but this did
      not reach statistical significance (15.63% versus 27.08%, p = .2379). Those
      having high transverse skin incisions had lower five minute median Apgar scores
      (8.0 versus 9.0, p = .0021), but no difference in umbilical artery pH values. The
      high transverse group also had increased NICU admissions (28.13% versus 5.21%, p
      = .0011), and early gestational age at delivery (36.8 versus 38.0, p = .0272).
      CONCLUSION: High transverse skin incisions may reduce the risk of wound
      complications in parturients with obesity. A study with more power should be
      considered.

PMID- 29020835
TI  - Quantifying benefits of using health information exchange to support public
      health STI reporting and treatment in Western New York.
AB  - OBJECTIVE: To calculate average savings of using health information exchange
      (HIE) for demographic and treatment requests for chlamydia and gonorrhoea in
      Western New York, specifically the Erie County Department of Health and its
      catchment area. METHOD: We conducted a mixed-method case study. Qualitative
      methods included interviews, document review, and workflow mapping, which were
      used as the inputs to identify time savings. Case rates, time savings, and salary
      averages were used to calculate average savings. RESULTS: The avoided demographic
      information requests resulted in time and money savings (range of USD$2312
      USD$4624 for chlamydia and USD$809-USD$1512 for gonorrhoea) as did avoided
      treatment requests (range of USD$671-USD$2803 for chlamydia and USD$981-USD$1635
      for gonorrhoea). DISCUSSION: HIE supported sexually transmitted infection (STI)
      treatment by making it easier for public health staff to identify and act upon
      STI diagnoses. Availability of information online resulted in less reliance on
      provider offices for demographic and treatment information. CONCLUSION: Results
      indicated that using HIE to support treatment and management of STIs can save
      public health staff time spent on obtaining demographic and treatment
      information. Other public health departments could use HIE for this and other
      types of disease surveillance activities. Considering public health needs in HIE
      development and use can improve efficiency of public health services and enhance
      effectiveness of activities.

PMID- 29020836
TI  - Are mental illnesses stigmatized for the same reasons? Identifying the stigma
      related beliefs underlying common mental illnesses.
AB  - BACKGROUND: Although mental health stigmatization has myriad pernicious
      consequences, it remains unknown whether mental disorders are stigmatized for the
      same reasons. AIMS: This study identified the stigma-related beliefs that were
      associated with several common mental illnesses (Study 1), and the extent to
      which those beliefs predicted stigmatization (Study 2). METHODS: In Study 1, we
      used multidimensional scaling to identify the stigma-related beliefs attributed
      to nine common mental disorders (e.g. depression, schizophrenia). Study 2
      explored whether beliefs commonly associated with depression predicted its
      stigmatization. RESULTS: In Study 1, we found that the nine mental illnesses
      differed from each other on two dimensions: social desirability and
      controllability. In Study 2, we found that regardless of participants' own
      depression status, their perceptions that depression is controllable predicted
      depression-related stigmatization. CONCLUSIONS: Our results suggest that
      stigmatization toward different mental illnesses stem from combinations of
      different stigmatized beliefs.

PMID- 29020837
TI  - Evaluating the completeness of the national ALS registry, United States.
AB  - Our objective was to evaluate the completeness of the United States National ALS
      Registry (Registry). We compared persons with ALS who were passively identified
      by the Registry with those actively identified in the State and Metropolitan Area
      ALS Surveillance project. Cases in the two projects were matched using a
      combination of identifiers, including, partial social security number, name, date
      of birth, and sex. The distributions of cases from the two projects that
      matched/did not match were compared and Chi-square tests conducted to determine
      statistical significance. There were 5883 ALS cases identified by the
      surveillance project. Of these, 1116 died before the Registry started, leaving
      4767 cases. We matched 2720 cases from the surveillance project to those in the
      Registry. The cases identified by the surveillance project that did not match
      cases in the Registry were more likely to be non-white, Hispanic, less than 65
      years of age, and from western states. The methods used by the Registry to
      identify ALS cases, i.e. national administrative data and self-registration,
      worked well but missed cases. These findings suggest that developing strategies
      to identify and promote the Registry to those who were more likely to be missing,
      e.g. non-white and Hispanic, could be beneficial to improving the completeness of
      the Registry.

PMID- 29020840
TI  - Self-determining medical leadership needs of occupational health physicians.
AB  - Purpose The purpose of this study was to explore which factors motivate doctors
      to engage in leadership roles and to frame an inquiry of self-assessment within
      Self-Determination Theory (SDT) to identify the extent to which a group of
      occupational health physicians (OHPs) was able to self-determine their leadership
      needs, using a National Health Service (NHS) England competency approach promoted
      by the NHS England Leadership Academy as a self-assessment leadership diagnostic.
      Medical leadership is seen as crucial to the transformation of health-care
      services, yet leadership programmes are often designed with a top-down and
      centrally commissioned "one-size-fits-all" approach. In the UK, the Smith Review
      (2015) concluded that more decentralised and locally designed leadership
      development programmes were needed to meet the health-care challenges of the
      future. However, there is an absence of empirical research to inform the design
      of effective strategies that will engage and motivate doctors to take up
      leadership roles, while at the same time, health-care organisations continue to
      develop formal leadership roles as a way to secure medical leadership engagement.
      The problem is further compounded by a lack of validated leadership qualities
      assessment instruments which support researching this problem.
      Design/Methodology/approach The analysis draws on a sample of about 25 per cent
      of the total population size of the Faculty of Occupational Medicine ( n =
      1,000). The questionnaire used was the Leadership Qualities Framework tool as a
      form of online self-assessment ( NHS Leadership Academy, 2012 ). The data were
      analysed using descriptive statistics and simple inferential methods. Findings
      OHPs are open about reporting their leadership strengths and leadership
      development needs and recognise leadership learning as an ongoing development
      need regardless of their level of personal competence. This study found that the
      single most important factor to affect a doctor's confidence in leadership is
      their experience in a management role. In multivariate regression, management
      experience accounted for the usefulness of leadership training, suggesting that
      doctors learn best through applied "leadership learning" as opposed to theory
      driven programmes. Drawing on SDT ( Deci and Ryan, 1985 ; 2000 ; Ryan and Deci,
      2000 ), this article provides a theoretical framework that helps to understand
      those doctors who are likely to engage in leadership and management activities in
      the organisation. More choice and self-determination of medical leadership
      programmes are likely to result in more relevant leadership learning that builds
      on doctors' previous experience in this area. Research limitations/implications
      While this study benefitted from a large sample size, it was limited to the use
      of purely quantitative methods. Future studies would benefit from the application
      of a mixed methodology to combine quantitative data with one-to-one interviews or
      a focus group. Practical implications This study suggests that doctors are able
      to determine their own learning needs reliably and that they are more likely to
      increase their confidence in leadership and management if they are exposed to
      leadership and management experience. Originality/value This is the first large
      scale study of this kind with a large sample within a single medical specialty.
      The study is considered as insider research, as the first author is an OHP with
      knowledge of how to engage OHPs in this work.

PMID- 29020839
TI  - Learning from the Longitudinal Outcomes of Children with Hearing Impairment
      (LOCHI) study: summary of 5-year findings and implications.
AB  - OBJECTIVE: This article summarises findings of the Longitudinal Outcomes of
      Children with Hearing Impairment (LOCHI) study, and discusses implications of the
      findings for research and clinical practice. DESIGN: A population-based study on
      outcomes of children with hearing loss. Evaluations were conducted at five years
      of age. STUDY SAMPLE: Participants were 470 children born with hearing loss
      between 2002 and 2007 in New South Wales, Victoria and Queensland in Australia,
      and who first received amplification or cochlear implantation by three years of
      age. RESULTS: The earlier hearing aids or cochlear implants were fitted, the
      better the speech, language and functional performance outcomes. Better speech
      perception was also associated with better language and higher cognitive
      abilities. Better psychosocial development was associated with better language
      and functional performance. Higher maternal education level was also associated
      with better outcomes. Qualitative analyses of parental perspectives revealed the
      multiple facets of their involvement in intervention. CONCLUSIONS: The LOCHI
      study has shown that early fitting of hearing devices is key to achieving better
      speech, language and functional performance outcomes for children with hearing
      loss. The findings are discussed in relation to changes in clinical practice and
      directions for future research.

PMID- 29020838
TI  - Safety and Efficacy of AAV5 Vectors Expressing Human or Canine CNGB3 in CNGB3
      Mutant Dogs.
AB  - Achromatopsia is an inherited retinal disorder of cone photoreceptors
      characterized by markedly reduced visual acuity, extreme light sensitivity, and
      absence of color discrimination. Approximately 50% of cases are caused by
      mutations in the cone photoreceptor-specific cyclic nucleotide gated channel beta
      subunit (CNGB3) gene. Studies in CNGB3-mutant dogs showed that subretinal
      injection of an AAV vector expressing human CNGB3, which has 76% amino acid
      identity with canine CNGB3, driven by a 2.1 kb human red cone opsin promoter
      (PR2.1) and packaged in AAV5 capsids (AAV5-PR2.1-hCNGB3) rescued cone
      photoreceptor function, but at high doses was associated with an inflammatory
      response (focal chorioretinitis) consistent with immune-mediated toxicity. AAV
      vectors containing the PR2.1 promoter packaged in AAV5 capsids and expressing
      either the native canine CNGB3 (AAV5-PR2.1-cCNGB3) or the human CNGB3 (AAV5-PR2.1
      hCNGB3) were evaluated at different dose levels in CNGB3-mutant dogs. The vector
      expressing canine CNGB3 achieved somewhat better rescue of cone function but
      unexpectedly was associated with a greater degree of retinal toxicity than the
      vector expressing human CNGB3. Very low-level T-cell immune responses to some AAV
      or CNGB3 peptides were observed in animals that received the higher vector dose.
      There was a more than twofold increase in serum neutralizing antibodies to AAV in
      one of three animals in the low-dose group and in two of three animals in the
      high-dose group. No serum anti-hCNGB3 antibodies were detected in any animal. The
      results of this study do not support the hypothesis that the focal
      chorioretinitis seen with high doses of AAV5-PR2.1-hCNGB3 in the initial studies
      was due to an immune response to human CNGB3.

PMID- 29020841
TI  - Empathy and privacy in obstetrics: Students abroad.

PMID- 29020842
TI  - Origins of School Nursing.
AB  - This study investigated the origin and implementation of school nursing in New
      York City, using traditional historical methods with a social history framework.
      The intent of this research was to produce a comprehensive historical analysis of
      school nursing at the turn of the 20th century in order to provide a historical
      framework to promote the work of school nurses today. Understanding the core
      fundamental concepts of school nursing from its origins and the significance of
      the emergence of community support for the role of the school nurse at the turn
      of the 20th century can inform current policy to back school nursing and school
      health today.

PMID- 29020843
TI  - Interview about the GIFT Trial, Pharmacogenetics, and Warfarin.

PMID- 29020844
TI  - Nucleoside/nucleotide analogues in the treatment of chronic hepatitis B infection
      during pregnancy: a systematic review.
AB  - BACKGROUND: Women of childbearing age who have developed chronic hepatitis B
      (CHB) infection, especially HBeAg-positive highly viraemic pregnant women, are
      largely responsible for the familial transmission of the infection. Therefore,
      choosing the most effective and safest antiviral medications to manage pregnant
      CHB patients is of crucial importance. MATERIALS AND METHODS: The PubMed and
      Scopus databases were searched through September 2017, for all the journal
      articles possessing original results regarding treatment of CHB pregnant women
      with any nucleos(t)ide analogue (NA) therapies, including lamivudine (LAM),
      adefovir (ADV), entecavir (ETV), telbivudine (LdT), and tenofovir (TDF). RESULTS:
      After the primary search, 882 studies were recognized, and updating the searching
      results, 41 journal articles with original data were investigated, involving 3874
      newborn infants from mothers with CHB, and their mothers completed follow-up
      until the delivery. The most important basic data and results regarding the
      efficacy of drugs, the rate of vertical transmission, safety issues associated
      with pairs of mothers and infants, median levels of HBV DNA, breastfeeding data,
      and rate of rate of vaccination success were collected. Moreover, possible key
      conclusion, recommendations, and learned lessons were discussed. Among the
      evaluated NAs, all LAM was efficient and safe. LdT was found to be very effective
      but had some safety concerns. In contrast, TDF had the advantages of both
      effectiveness and safety. CONCLUSION: According to data in the literature,
      initiation of TDF at the trimester of pregnancy in combination with
      immunoprophylaxis to prevent mother-to-child transmission (MTCT) of CHB infection
      is strongly recommended as well as successful immunization of CHB pregnant women
      by anti-HBV vaccines.

PMID- 29020845
TI  - End-of-Life Caregiver Social Support Activation: The Roles of Hospice Clinicians
      and Professionals.
AB  - Caregivers of those with life-limiting illness face many complicated tasks,
      including providing direct patient care, communicating with professionals, and
      managing the logistical demands of daily activities. To assist with caregiving
      responsibilities, caregivers require social support from social network members
      at all points in the illness process. This study analyzes themes from interviews
      with 61 caregivers of patients enrolled in hospice services to identify the types
      of support caregivers mobilize from new social network members for social support
      during the end-of-life care process. Themes indicate that caregivers receive
      accessible, immediate, caregiver-centered emotional support from hospice health
      care professionals, and situationally tailored, understandable informational
      support from other types of professionals. In addition, caregivers received
      overlapping emotional and informational support from hospice health care
      professionals. Findings enhance the understanding of how caregivers receive
      tailored emotional and informational support.

PMID- 29020847
TI  - Sphingolipids and microRNA Changes in Blood following Blast Traumatic Brain
      Injury: An Exploratory Study.
AB  - At present, accurate and reliable biomarkers to ascertain the presence, severity,
      or prognosis of blast traumatic brain injury (bTBI) are lacking. There is an
      urgent need to establish accurate and reliable biomarkers capable of mbTBI
      detection. Currently, there are no studies that identify changes in miRNA and
      lipids at varied severities of bTBI. Various biological components such as
      lipids, circulating mRNA, and miRNA, could potentially be detected using advanced
      techniques such as next-generation sequencing and mass spectroscopy. Therefore,
      plasma analysis is an attractive approach with which to diagnose and treat brain
      injuries. Subacute changes in plasma microRNA (miRNA) and lipid composition for
      sphingolipids were evaluated in a murine model of mild-to-moderate bTBI using
      next-generation sequencing and mass spectroscopy respectively. Animals were
      exposed at 17, 17 * 3, and 20 psi blast intensities using a calibrated blast
      simulator. Plasma lipid profiling demonstrated decreased C18 fatty acid chains of
      sphingomyelins and increased ceramide levels when compared with controls. Plasma
      levels of brain-enriched miRNA, miR-127 were increased in all groups while let
      7a, b, and g were reduced in the 17 * 3 and 20 psi groups, but let 7d was
      increased in the 17 psi group. The majority of the miRs and lipids are highly
      conserved across different species, making them attractive to explore and
      potentially employ as diagnostic markers. It is tempting to speculate that
      sphingolipids, miR-128, and the let-7 family could predict mTBI, while a
      combination of miR-484, miR-122, miR-148a, miR-130a, and miR-223 could be used to
      predict the overall status of injury following blast injury.

PMID- 29020846
TI  - Patients' and caregivers' needs, experiences, preferences and research priorities
      in spiritual care: A focus group study across nine countries.
AB  - BACKGROUND: Spiritual distress is prevalent in advanced disease, but often
      neglected, resulting in unnecessary suffering. Evidence to inform spiritual care
      practices in palliative care is limited. AIM: To explore spiritual care needs,
      experiences, preferences and research priorities in an international sample of
      patients with life-limiting disease and family caregivers. DESIGN: Focus group
      study. SETTING/PARTICIPANTS: Separate patient and caregiver focus groups were
      conducted at 11 sites in South Africa, Kenya, South Korea, the United States,
      Canada, the United Kingdom, Belgium, Finland and Poland. Discussions were
      transcribed, translated into English and analysed thematically. RESULTS: A total
      of 74 patients participated: median age 62 years; 53 had cancer; 48 were women.
      In total, 71 caregivers participated: median age 61 years; 56 were women. Two
      thirds of participants were Christian. Five themes are described: patients' and
      caregivers' spiritual concerns, understanding of spirituality and its role in
      illness, views and experiences of spiritual care, preferences regarding spiritual
      care, and research priorities. Participants reported wide-ranging spiritual
      concerns spanning existential, psychological, religious and social domains.
      Spirituality supported coping, but could also result in framing illness as
      punishment. Participants emphasised the need for staff competence in spiritual
      care. Spiritual care was reportedly lacking, primarily due to staff members' de
      prioritisation and lack of time. Patients' research priorities included
      understanding the qualities of human connectedness and fostering these skills in
      staff. Caregivers' priorities included staff training, assessment, studying
      impact, and caregiver's spiritual care needs. CONCLUSION: To meet patient and
      caregiver preferences, healthcare providers should be able to address their
      spiritual concerns. Findings should inform patient- and caregiver-centred
      spiritual care provision, education and research.

PMID- 29020848
TI  - Concussion Alters the Functional Brain Processes of Visual Attention and Working
      Memory.
AB  - Millions of North Americans sustain a concussion or a mild traumatic brain injury
      annually, and are at risk of cognitive, emotional, and physical sequelae.
      Although functional MRI (fMRI) studies have provided an initial framework for
      examining functional deficits induced by concussion, particularly working memory
      and attention, the temporal dynamics underlying these deficits are not well
      understood. We used magnetoencephalography (MEG), a modality with millisecond
      temporal resolution, in conjunction with a 1-back visual working memory (VWM)
      paradigm using scenes from everyday life to characterize spatiotemporal
      functional differences at specific VWM stages, in adults had had or had not had a
      recent concussion. MEG source-level differences between groups were determined by
      whole-brain analyses during encoding and recognition phases. Despite comparable
      behavioral performance, abnormal hypo- and hyperactivation patterns were found in
      brain areas involving frontoparietal, ventral occipitotemporal, temporal, and
      subcortical areas in concussed patients. These patterns and their timing varied
      as a function of VWM stagewise processing, linked to early attentional control,
      visuoperceptual scene processing, and VWM maintenance and retrieval processes.
      Parietal hypoactivation, starting at 60 ms during encoding, was correlated with
      symptom severity, possibly linked to impaired top-down attentional processing.
      Hyperactivation in the scene-selective occipitotemporal areas, the medial
      temporal complex, specifically the right hippocampus and orbitofrontal areas
      during encoding and/or recognition, lead us to posit inefficient but compensatory
      visuoperceptual, relational, and retrieval processing. Although injuries
      sustained after the concussion were considered "mild," these data suggest that
      they can have prolonged effects on early attentional and VWM processes.

PMID- 29020849
TI  - Microfluidic preparation of drug-loaded PEGylated liposomes, and the impact of
      liposome size on tumour retention and penetration.
AB  - Understanding the effect of liposome size on tendency for accumulation in tumour
      tissue requires preparation of defined populations of different sized particles.
      However, controlling the size distributions without changing the lipid
      composition is difficult, and differences in compositions itself modify
      distribution behaviour. Here, a commercial microfluidic format as well as
      traditional methods was used to prepare doxorubicin-loaded liposomes of different
      size distributions but with the same lipid composition, and drug retention,
      biodistribution and localization in tumour tissues were evaluated. The small (~50
      nm diameter) liposomes prepared by microfluidics and large (~75 nm diameter)
      liposomes displayed similar drug retention in in vitro release studies, and
      similar biodistribution patterns in tumour-bearing mice. However, the extent of
      extravasation was clearly dependent on size of the liposomes, with the small
      liposomes showing tissue distribution beyond the vascular area compared to the
      large liposomes. The use of microfluidics to prepare smaller size distribution
      liposomes compared to sonication methods is demonstrated, and allowed preparation
      of different size distribution drug carriers from the same lipid composition to
      enable new understanding of tissue distribution in compositionally consistent
      materials is demonstrated.

PMID- 29020850
TI  - Household food security and HIV status in rural and urban communities in the Free
      State province, South Africa.
AB  - Higher socioeconomic status impacts profoundly on quality of life. Life-event
      stressors, such as loss of employment, marital separation/divorce, death of a
      spouse and food insecurity, have been found to accelerate disease progression
      among people with human immunodeficiency virus (HIV). The objective of this study
      was to determine significant independent sociodemographic and food security
      factors associated with HIV status in people from rural and urban communities in
      the Assuring Health for All study, which was undertaken in rural Trompsburg,
      Philippolis and Springfontein and urban Mangaung, in the Free State Province of
      South Africa. Sociodemographic and food security factors associated with HIV
      status were determined in 886 households. Logistic regression with forward
      selection (p < 0.05) was used to select significant independent factors
      associated with HIV status. Variables with a p-value of <0.15 were considered for
      inclusion in the model. Adults 25-64 years of age were eligible to participate.
      Of the 567 rural participants, 97 (17.1%) were HIV-infected, and 172 (40.6%) of
      the 424 urban participants. A relatively high percentage of respondents had never
      attended school, while very few participants in all areas had a tertiary
      education. The unemployment rate of HIV-infected adults was higher than that of
      HIV-uninfected adults. A high percentage of respondents in all areas reported
      running out of money to buy food, with this tendency occurring significantly more
      among urban HIV-infected than HIV-uninfected respondents. In all areas, a high
      percentage of HIV-infected respondents relied on a limited number of foods to
      feed their children, with significantly more HIV-infected urban respondents
      compared to their uninfected counterparts reporting this. Most participants in
      all areas had to cut the size of meals, or ate less because there was not enough
      food in the house or not enough money to buy food. During periods of food
      shortage, more than 50% of respondents in all areas asked family, relatives or
      neighbours for assistance with money and/or food, which occurred at a higher
      percentage of HIV-infected rural participants compared to HIV-uninfected rural
      participants. More than half of all participants reported feeling sad, blue or
      depressed for two weeks or more in a row. HIV infection was negatively associated
      with being married (odds ratio 0.20 in rural areas and 0.54 in urban areas),
      while church membership decreased the likelihood of HIV (odds ratio 0.22 in rural
      areas and 0.46 in urban areas). Indicators of higher socioeconomic status (having
      a microwave oven and access to vegetables from local farmers or shops) decreased
      the likelihood of HIV in rural areas (odds ratios 0.15 and 0.43, respectively).
      Indicators of lower socioeconomic status such as spending less money on food in
      the rural sample (odds ratio 3.29) and experiencing periods of food shortages in
      the urban sample (odds ratio 2.14), increased the likelihood of being HIV
      infected. Interventions aimed at poverty alleviation and strengthening values can
      contribute to addressing HIV infection in South Africa.

PMID- 29020851
TI  - Impact of Attending the Diwaniyyah on Kuwaiti Men's Health.
AB  - Diwaniyyah is a traditional gathering place for men in the Arab world. Most
      Kuwaiti men spend most of their time in the diwaniyyah, which is an important
      part of their social activity. The current study aims to examine the relationship
      between the diwaniyyah as a social community and the attendees' health conditions
      to determine how the diwaniyyah affects Kuwaiti men's lifestyle. A questionnaire
      was distributed among 500 men 16 years old and above. It comprised five parts of
      data: sociodemographic information, frequency of attending diwaniyyah, types of
      diwaniyyahs, and health lifestyle of members attending the diwaniyyah. A t-test,
      one-way analysis of variance (ANOVA) and linear regression were used to test the
      study's questions. A significant difference in negative effect of diwaniyyahs on
      attendees' physical health was detected according to the participants' ethnic
      roots, affection for and length of time they spent in the diwaniyyah, time of day
      or evening that they visited, and dealing with chronic disease ( p < .05). Also
      the results reveal significant differences in the positive effect of diwaniyyahs
      on the attendees' lifestyle behavior according to their age, occupational status,
      religious affiliation, government, prayer time, and type of diwaniyyah ( p <
      .05).

PMID- 29020852
TI  - Response to: Situational judgment tests: Who knows the right answers?

PMID- 29020853
TI  - Blood-Based Protein Biomarkers for the Management of Traumatic Brain Injuries in
      Adults Presenting to Emergency Departments with Mild Brain Injury: A Living
      Systematic Review and Meta-Analysis.
AB  - Accurate diagnosis of traumatic brain injury (TBI) is critical to effective
      management and intervention, but can be challenging in patients with mild TBI. A
      substantial number of studies have reported the use of circulating biomarkers as
      signatures for TBI, capable of improving diagnostic accuracy and clinical
      decision making beyond current practice standards. We performed a systematic
      review and meta-analysis to comprehensively and critically evaluate the existing
      body of evidence for the use of blood protein biomarkers (S100 calcium binding
      protein B [S100B], glial fibrillary acidic protein [GFAP], neuron specific
      enolase [NSE], ubiquitin C-terminal hydrolase-L1 [UCH-L1]. tau, and neurofilament
      proteins) for diagnosis of intracranial lesions on CT following mild TBI. Effects
      of potential confounding factors and differential diagnostic performance of the
      included markers were explored. Further, appropriateness of study design,
      analysis, quality, and demonstration of clinical utility were assessed. Studies
      published up to October 2016 were identified through a MEDLINE(r), Embase, and
      Cumulative Index to Nursing and Allied Health Literature (CINAHL) search.
      Following screening of the identified articles, 26 were selected as relevant. We
      found that measurement of S100B can help informed decision making in the
      emergency department, possibly reducing resource use; however, there is
      insufficient evidence that any of the other markers is ready for clinical
      application. Our work pointed out serious problems in the design, analysis, and
      reporting of many of the studies, and identified substantial heterogeneity and
      research gaps. These findings emphasize the importance of methodologically
      rigorous studies focused on a biomarker's intended use, and defining
      standardized, validated, and reproducible approaches. The living nature of this
      systematic review, which will summarize key updated information as it becomes
      available, can inform and guide future implementation of biomarkers in the
      clinical arena.

PMID- 29020854
TI  - Shared decision-making at the end of life: A focus group study exploring the
      perceptions and experiences of multi-disciplinary healthcare professionals
      working in the home setting.
AB  - BACKGROUND: Globally recommended in healthcare policy, Shared Decision-Making is
      also central to international policy promoting community palliative care. Yet
      realities of implementation by multi-disciplinary healthcare professionals who
      provide end-of-life care in the home are unclear. AIM: To explore multi
      disciplinary healthcare professionals' perceptions and experiences of Shared
      Decision-Making at end of life in the home. DESIGN: Qualitative design using
      focus groups, transcribed verbatim and analysed thematically.
      SETTING/PARTICIPANTS: A total of 43 participants, from multi-disciplinary
      community-based services in one region of the United Kingdom, were recruited.
      RESULTS: While the rhetoric of Shared Decision-Making was recognised, its
      implementation was impacted by several interconnecting factors, including (1)
      conceptual confusion regarding Shared Decision-Making, (2) uncertainty in the
      process and (3) organisational factors which impeded Shared Decision-Making.
      CONCLUSION: Multiple interacting factors influence implementation of Shared
      Decision-Making by professionals working in complex community settings at the end
      of life. Moving from rhetoric to reality requires future work exploring the
      realities of Shared Decision-Making practice at individual, process and systems
      levels.

PMID- 29020855
TI  - Retrospective chart evaluation of hypercalcemia management in oncology patients
      at the University of Chicago Medical Center.
AB  - Introduction Due to the lack of formal guideline recommendations, available
      primary literature was used to develop a proposed protocol for management of
      hypercalcemia of malignancy at the University of Chicago Medical Center. Methods
      A retrospective, single center, observational study was performed including adult
      patients hospitalized with a diagnosis of hypercalcemia and active malignancy.
      Patients were retrospectively identified as treated in a manner aligned with the
      proposed protocol ("per protocol") or not treated according to the proposed
      protocol ("off protocol"), and the outcomes were compared. The primary outcome
      for efficacy was normalization of corrected calcium within four and seven days of
      treatment. Results Normalization of corrected calcium was observed in 66% of
      patients managed per protocol compared to 65% of patients managed off protocol (
      p = 1.00) at day four, and in 73% of per protocol patients compared to 65% of off
      protocol patients ( p = 0.44) at day seven. Areas identified where prospective
      implementation of the proposed protocol can improve management include:
      decreasing utilization of bisphosphonates in mild hypercalcemia, optimizing
      bisphosphonate dosing in renal impairment, decreasing intravenous phosphate
      repletion, and ensuring proper fluid management and calcitonin dosing. Conclusion
      Although a statistical difference was not detected in terms of normalization of
      corrected calcium levels, areas for optimization in management were identified.
      Therefore, implementation of the proposed protocol is expected to promote
      evidence-based management of hypercalcemia of malignancy management at University
      of Chicago Medical Center.

PMID- 29020856
TI  - Hepatitis C infection and chemotherapy toxicity.
AB  - There exists little guidance on chemotherapy toxicity management in patients with
      a history of or active hepatitis C viral infection. We report four cases of
      patients with solid organ tumors and hepatitis C viral infection, who have
      experienced severe or unexpected toxicities with chemotherapy. Based on the four
      case reports, we recommend increased laboratory monitoring for toxicities,
      initial dose reductions for chemotherapy given with palliative intent, or pre
      emptive use of growth factor support, even if the patient presents with normal
      liver function tests. In this patient population, we also recommend treating
      active hepatitis C viral infection prior to chemotherapy treatment when possible.

PMID- 29020857
TI  - Optimizing patient education of oncology medications: A descriptive survey of
      pharmacist-provided patient education in Canada.
AB  - Background The incidence of cancer is increasing in Canada due to an aging and
      growing population. This frequently necessitates chemotherapy, which is a high
      risk treatment, often given as a part of a complex regimen with serious side
      effects. A review of the evidence of pharmacy-provided patient education
      initiatives targeted to oncology patients revealed that minimal is known about
      this service. Objective The objective of this study was to determine the
      different models of patient education of oncology medications delivered by
      pharmacists to adult oncology patients in a hospital or cancer center in Canada.
      Methods The study design was a descriptive online survey developed by the
      investigation team and was distributed to pharmacists who provided patient
      education to adult oncology patients. The primary outcome of this research
      project was to describe self-reported pharmacist-provided patient education of
      oncology medications across Canada. The survey data was analyzed quantitatively
      with Opinio survey software. Results Sixty-four pharmacists completed the survey.
      Key findings of the study were that approximately 50% of pharmacists spend up to
      25% of their time providing direct patient care and that not all adult oncology
      patients are receiving education by a pharmacist. Conclusions Pharmacists provide
      patient education at the first treatment, change in therapy, and on request of
      another healthcare professional. Most cover administration, side effects, their
      prevention and management, and drug-interactions. Frequently used teaching
      methods include structured patient education delivery process, customized
      teaching for each patient, and repetition of key educational points.

PMID- 29020858
TI  - Comment on: Essential competencies in global health research for medical
      trainees: A narrative review.

PMID- 29020859
TI  - Conditional deletion of Pip5k1c in sensory ganglia and effects on nociception and
      inflammatory sensitization.
AB  - Abstract: Phosphatidylinositol 4-phosphate 5-kinase type 1 gamma (Pip5k1c)
      generates phosphatidylinositol 4,5-bisphosphate, alsoknown as PI(4,5)P2 or PIP2.
      Many pronociceptive signaling pathways and receptor tyrosine kinases signal via
      PIP2 hydrolysis.Previously, we found that pain signaling and pain sensitization
      were reduced in Pip5k1cp/ global heterozygous knockoutmice. Here, we sought to
      evaluate the extent to which dorsal root ganglia selective deletion of Pip5k1c
      affected nociceptionin mice. Initially, we crossed sensory neuron-selective
      Advillin-Cre mice with a conditional Pip5k1c knockout (cKO) allele(Pip5k1cfl/fl).
      However, these mice displayed an early onset proprioceptive deficit. To bypass
      this early onset phenotype,we used two different tamoxifen-inducible Cre lines
      (Brn3a-Cre-ERT2 and Advillin-Cre-ERT2) to conditionally delete Pip5k1c inadults.
      Tamoxifen induced high efficiency deletion of PIP5K1C in dorsal root ganglia and
      slightly reduced PIP5K1C in spinalcord and brain in Brn3a-Cre-ERT2  Pip5k1cfl/fl
      (Brn3a cKO) mice while PIP5K1C was selectively deleted in dorsal root gangliawith
      no changes in spinal cord or brain in Advillin-Cre-ERT2  Pip5k1cfl/fl (Advil cKO)
      mice. Acute thermosensation andmechanosensation were not altered in either line
      relative to wild-type mice. However, thermal hypersensitivity and
      mechanicalallodynia recovered more rapidly in Brn3a cKO mice, but not Advil cKO
      mice, following hind paw inflammation.These data collectively suggest that
      PIP5K1C regulates nociceptive sensitization in more regions of the nervous
      systemthan dorsal root ganglia alone.

PMID- 29020862
TI  - Moving Home: Examining the Independent Effects of Individual- and Neighborhood
      Level Residential Mobility on Recidivism in High-Risk Parolees.
AB  - A number of studies have shown that the residential mobility of an offender
      postrelease can significantly influence recidivism. Research has also shown how
      the mobility of neighborhoods into which offenders are released is an important
      contextual factor that predicts recidivism. Within the social disorganization
      framework, this study combines these lines of research by examining the effect of
      both individual- and neighborhood-level residential mobility on recidivism for a
      cohort of high-risk prisoners released on parole in New Zealand. Using multilevel
      analysis techniques, we found that neither immediate individual-level residential
      mobility nor neighborhood-level mobility was associated with recidivism after
      controlling for various multilevel predictors. A number of individual- and
      neighborhood-level variables were predictive of recidivism, including the number
      of parole conditions placed on the released offender, and the percent foreign
      born in their neighborhood. These results are discussed within the context of an
      increasingly eclectic and diverse country.

PMID- 29020860
TI  - Group I metabotropic glutamate receptor plasticity after peripheral inflammation
      alters nociceptive transmission in the dorsal of the spinal cord in adult rats.
AB  - Abstract: The dorsal horn of the spinal cord is a crucial site for pain
      transmission and modulation. Dorsal horn neurons of the spinal cord express group
      I metabotropic glutamate receptors (group I mGluRs) that exert a complex role in
      nociceptive transmission. In particular, group I mGluRs promote the activation of
      L-type calcium channels, voltage-gated channels involved in short- and long-term
      sensitization to pain. In this study, we analyzed the role of group I mGluRs in
      spinal nociceptive transmission and the possible cooperation between these
      receptors and L-type calcium channels in the pathophysiology of pain transmission
      in the dorsal horn of the spinal cord. We demonstrate that the activation of
      group I mGluRs induces allodynia and L-type calcium channel-dependent increase in
      nociceptive field potentials following sciatic nerve stimulation. Surprisingly,
      in a model of persistent inflammation induced by complete Freund's adjuvant, the
      activation of group I mGluRs induced an analgesia and a decrease in nociceptive
      field potentials. Among the group I mGluRs, mGluR1 promotes the activation of L
      type calcium channels and increased nociceptive transmission while mGluR5 induces
      the opposite through the inhibitory network. These results suggest a functional
      switch exists in pathological conditions that can change the action of group I
      mGluR agonists into possible analgesic molecules, thereby suggesting new
      therapeutic perspectives to treat persistent pain in inflammatory settings.

PMID- 29020861
TI  - Psilocybin-occasioned mystical-type experience in combination with meditation and
      other spiritual practices produces enduring positive changes in psychological
      functioning and in trait measures of prosocial attitudes and behaviors.
AB  - Psilocybin can occasion mystical-type experiences with participant-attributed
      increases in well-being. However, little research has examined enduring changes
      in traits. This study administered psilocybin to participants who undertook a
      program of meditation/spiritual practices. Healthy participants were randomized
      to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2)
      with moderate-level ("standard") support for spiritual-practice (LD-SS); (2) high
      dose (20 and 30 mg/70 kg on sessions 1 and 2, respectively) with standard support
      (HD-SS); and (3) high-dose (20 and 30 mg/70kg on sessions 1 and 2, respectively)
      with high support for spiritual practice (HD-HS). Psilocybin was administered
      double-blind and instructions to participants/staff minimized expectancy
      confounds. Psilocybin was administered 1 and 2 months after spiritual-practice
      initiation. Outcomes at 6 months included rates of spiritual practice and
      persisting effects of psilocybin. Compared with low-dose, high-dose psilocybin
      produced greater acute and persisting effects. At 6 months, compared with LD-SS,
      both high-dose groups showed large significant positive changes on longitudinal
      measures of interpersonal closeness, gratitude, life meaning/purpose,
      forgiveness, death transcendence, daily spiritual experiences, religious faith
      and coping, and community observer ratings. Determinants of enduring effects were
      psilocybin-occasioned mystical-type experience and rates of meditation/spiritual
      practices. Psilocybin can occasion enduring trait-level increases in prosocial
      attitudes/behaviors and in healthy psychological functioning. Trial Registration
      ClinicalTrials.gov Identifier NCT00802282.

PMID- 29020863
TI  - Examining Employment Outcomes of Offender and Nonoffender Vocational Program
      Graduates.
AB  - Researchers have found providing employment opportunities for ex-offenders
      through job training programs to be effective at reducing recidivism. Examining
      various community-based programs for ex-offenders can be beneficial as they may
      be able to provide more stable and consistent programming without relying on the
      justice system. This study examined employment outcomes of graduates with and
      without criminal histories ( n = 617) from a community-based vocational training
      program. Results showed that ex-offender graduates obtained employment at equal
      rates to nonoffender graduates and received equal pay to their nonoffender
      counterparts. This could indicate that for the vocationally educated ex-offender,
      employment outcomes may be able to equal those of other job-searching individuals
      with similar backgrounds but without a criminal history. Community-based programs
      for ex-offenders may be able to provide effective programming to improve
      vocational attainment within this group, thereby potentially easing the burden on
      criminal justice institutions as the sole provider of offender rehabilitation.

PMID- 29020864
TI  - End-of-life care: A qualitative study comparing the views of people with dementia
      and family carers.
AB  - BACKGROUND: In recent years, UK policy has increasingly recognised the importance
      of end-of-life care in dementia. While professional consensus on optimal
      palliative care in dementia has been reported, little is known about the
      perspectives of people with dementia and family carers. AIM: To compare the views
      of people with dementia and family carers of people with dementia (current and
      recently bereaved) on optimal end-of-life care. DESIGN: Qualitative interviews
      (32) and a focus group were conducted. Data were thematically analysed.
      SETTING/PARTICIPANTS: Participants comprised people with early stage dementia,
      living at home in the north-east of England ( n = 11); and current and bereaved
      carers ( n = 25) from six services providing end-of-life care in England.
      FINDINGS: Seven areas were identified as important to end-of-life care for people
      with dementia and/or family carers. People with dementia and carers expressed the
      need for receiving care in place, ensuring comfort and a skilled care team.
      However, they disagreed about the importance of planning for the future and the
      role of families in organising care and future decision-making. CONCLUSION:
      Further comparison of our findings with expert consensus views highlighted key
      areas of divergence and agreement. Discordant views concerning perceptions of
      dementia as a palliative condition, responsibility for future decision-making and
      the practical co-ordination of end-of-life care may undermine the provision of
      optimal palliative care. Professionals must explore and recognise the individual
      perspectives of people with dementia and family carers.

PMID- 29020865
TI  - Peer-to-peer shadowing as a technique for the development of nurse middle
      managers clinical leadership.
AB  - Purpose The purpose of this study was to explore the experiences and impact of
      peer-to-peer shadowing as a technique to develop nurse middle managers' clinical
      leadership practices. Design/methodology/approach A qualitative descriptive study
      was conducted to gain insight into the experiences of nurse middle managers using
      semi-structured interviews. Data were analysed into codes using constant
      comparison and similar codes were grouped under sub-themes and then into four
      broader themes. Findings Peer-to-peer shadowing facilitates collective reflection
      in-action and enhances an "investigate stance" while acting. Nurse middle
      managers begin to curb the caring disposition that unreflectively urges them to
      act, to answer the call for help in the here and now, focus on ad hoc "doings",
      and make quick judgements. Seeing a shadowee act produces, via a process of
      social comparison, a behavioural repertoire of postponing reactions and
      refraining from judging. Balancing the act of stepping in and doing something or
      just observing as well as giving or withholding feedback are important practices
      that are difficult to develop. Originality/value Peer-to-peer shadowing
      facilitates curbing the caring disposition, which is essential for clinical
      leadership development through unlocking a behavioural repertoire that is not
      easy to reveal because it is, unreflectively, closely knit to the professional
      background of the nurse managers. Unlike most leadership development programmes,
      that are quite introspective and detached from context, peer-to-peer shadowing
      does have the potential to promote collective learning while acting, which is an
      important process.

PMID- 29020866
TI  - Cause and timing of death and sub-group differential effects of erythropoietin in
      the EPO-TBI study.
AB  - The EPO-TBI study randomised 606 patients with moderate or severe traumatic brain
      injury (TBI) to be treated with weekly epoetin alfa (EPO) or placebo. Six-month
      mortality was lower in EPO treated patients in an analysis adjusting for TBI
      severity. Knowledge of possible differential effects by TBI injury subtype and
      acute neurosurgical treatment as well as timing and cause of death (COD) will
      facilitate the design of future interventional TBI trials. We defined COD as
      cerebral (brain death, cerebral death with withdrawal or death during maximal
      care) and non-cerebral (death following withdrawal or during maximal care due to
      a non-cerebral cause). The study included 305 patients treated with EPO and 297
      with placebo, with COD recorded in 77 (99%) out of 78 non-survivors. Median time
      to death in patients dying of cerebral COD was 8 days (IQR 5-16) compared to 29
      days (IQR 7-56) (p=0.01) with non-cerebral COD. When assessing subgroups by
      admission computed tomography scan injury findings, we found no significant
      differential effects of EPO compared to placebo. However, EPO appeared more
      effective in patients with an injury type not requiring a neurosurgical operation
      prior to ICU admission (OR 0.29, 95% confidence interval 0.14-0.61, p=0.001, p
      for interaction = 0.003) and in this sub-group, fewer patients died of cerebral
      causes in in the EPO compared to placebo group (5% compared to 14%, p=0.03). In
      conclusion, most TBI deaths were due to cerebral causesthat occurred during the
      first two weeks, and were related to withdrawal of care. EPO appeared to
      specifically reduce cerebral deaths in the important subgroup of patients with a
      diffuse type of injury not requiring a neurosurgical intervention prior to
      randomisation.

PMID- 29020867
TI  - Activation of the Behavioral Immune System: Putting the Brakes on Affiliation.
AB  - Evolutionary psychologists propose that humans evolved a first line of defense
      against pathogens: the behavioral immune system (BIS). The BIS is thought to be
      functionally flexible such that the likelihood and magnitude of BIS activation
      depends on the individual's perceived vulnerability to disease (PVD). Because
      conspecifics are sources of infection, the BIS has implications for affiliation.
      By priming and measuring chronic levels of PVD, we examined PVD's relation to
      affiliation in zero-acquaintance situations in the laboratory, online, and during
      speed-dating events. Elevated BIS activation was associated with decreased
      attraction and affiliative behavior in situations that varied in the trade-off
      between social reward and potential risk of infection. These results were not due
      to attachment style, personality traits, or disgust sensitivity. This suggests
      that in social interactions, approach motivation associated with the need to
      belong may be weighed against avoidance motivation associated with the need to
      protect the self from disease.

PMID- 29020868
TI  - Extended pelvic lymph-node dissection and radiotherapy with curative intent in
      high-risk lymph-node-positive prostate cancer: a possible curative strategy?
AB  - OBJECTIVE: This study evaluated the outcome with a treatment strategy for high
      risk prostate cancer (PCa) using extended pelvic lymph-node dissection (eLND)
      followed by external beam radiation therapy (EBRT) in lymph-node-positive (LNpos)
      and lymph-node-negative (LNneg) cases compared with the strategy with limited
      pelvic lymph-node dissection (lLND) and only giving EBRT to LNneg cases.
      MATERIALS AND METHODS: From 2000 to 2006, 124 men with high-risk PCa underwent
      lLND and initiated androgen deprivation therapy (ADT) before planned EBRT. LNpos
      patients were excluded from EBRT following the SPCG-7 study strategy (group I).
      From 2007 to 2013, 111 patients underwent eLND and started ADT before EBRT, and
      LNneg and most LNpos patients received EBRT (group II). Using Kaplan-Meier plots
      and multivariable Cox regression, biochemical recurrence-free, metastasis-free,
      cancer-specific survival and overall survival were compared during a 10 year
      follow-up. RESULTS: PSA progression-free survival rates after 2, 4, 6, 8 and 10
      years were 78%, 66%, 52%, 45% and 41% in group I, and 88%, 83%, 78%, 69% and 69%
      in group II (p < 0.001), respectively. Group II had a lower risk of PSA
      progression [hazard ratio (HR) = 0.43, 95% confidence interval (CI) 0.27,0.69, p
      = 0.001], metastasis development (HR = 0.51, 95% CI 0.27,0.97, p = 0.040) and
      overall mortality (HR = 0.49, 95% CI 0.26,0.92, p = 0.027), but not of PCa
      specific death (HR = 0.45, 95% CI 0.19,1.08, p = 0.074). CONCLUSION: A treatment
      strategy for high-risk PCa with eLND combined with EBRT in LNneg and LNpos cases
      may improve outcome compared to a strategy with lLND and offering EBRT only to
      LNneg cases but ADT to LNpos cases.

PMID- 29020869
TI  - A Review of Four Health Procedures That School Nurses May Encounter.
AB  - The school nurse plays a vital role in providing care and meeting the health
      needs of students in the school setting. Students attend school with chronic
      conditions and complex medical problems such as quadriplegia, cerebral palsy,
      spina bifida, and muscular dystrophy. It is the responsibility of the school
      nurse to provide appropriate assessment, early intervention, and care for
      children in the school environment. The purpose of this article is to review and
      discuss the knowledge and skills the school nurse needs to care for students with
      central venous lines, gastrostomy tubes, altered urinary elimination, and
      tracheostomies.

PMID- 29020870
TI  - Recent life stress exposure is associated with poorer long-term memory, working
      memory, and self-reported memory.
AB  - Although substantial research has examined the effects of stress on cognition,
      much of this research has focused on acute stress (e.g. manipulated in the
      laboratory) or chronic stress (e.g. persistent interpersonal or financial
      difficulties). In contrast, the effects of recent life stress on cognition have
      been relatively understudied. To address this issue, we examined how recent life
      stress is associated with long-term, working memory, and self-reported memory in
      a sample of 142 healthy young adults who were assessed at two time points over a
      two-week period. Recent life stress was measured using the newly-developed Stress
      and Adversity Inventory for Daily Stress (Daily STRAIN), which assesses the
      frequency of relatively common stressful life events and difficulties over the
      preceding two weeks. To assess memory performance, participants completed both
      long-term and working memory tasks. Participants also provided self-reports of
      memory problems. As hypothesized, greater recent life stress exposure was
      associated with worse performance on measures of long-term and working memory, as
      well as more self-reported memory problems. These associations were largely
      robust while controlling for possible confounds, including participants' age,
      sex, and negative affect. The findings indicate that recent life stress exposure
      is broadly associated with worse memory. Future studies should thus consider
      assessing recent life stress as a potential predictor, moderator, or covariate of
      memory performance.

PMID- 29020873
TI  - Palmaris longus tendocutaneous arterialized venous free flap to reconstruct the
      interphalangeal collateral ligament in composite defects.
AB  - : We present 12 cases in which palmaris longus tendocutaneous arterialized venous
      free flaps were used for the reconstruction of the collateral ligament in
      compound defects of digits. There were nine cases involving the interphalangeal
      joint of the fingers and three of the interphalangeal joints of the thumb. The
      venous flaps survived completely in 10 of the 12 cases. In 11 cases, there were
      excellent functional results for joint stability, pain, total active motion and
      pinch power. In all 12 cases, a pain-free joint with excellent stability was
      achieved after surgery. The palmaris longus tendocutaneous arterialized venous
      free flap is a good option for reconstruction of composite defects of the
      collateral ligament of the interphalangeal joint. LEVEL OF EVIDENCE: IV.

PMID- 29020872
TI  - Paediatric tuberculous osteomyelitis of the thumb metacarpal bone.

PMID- 29020871
TI  - Tolerability and safety of the intravenous immunoglobulin octagam(r) 10% in
      patients with immune thrombocytopenia: a post-authorisation safety analysis of
      two non-interventional phase IV trials.
AB  - OBJECTIVES: To provide detailed data on the tolerability and safety of octagam(r)
      10%, a ready-to-use intravenous immunoglobulin, in a subgroup of patients with
      immune thrombocytopenia (ITP) involved in an integrated analysis of post
      authorisation safety surveillance (PASS) studies. METHODS: A subgroup analysis
      was conducted using data collected from two non-interventional studies that
      included patients with ITP treated with octagam(r) 10%. Patients were observed
      and monitored for possible adverse drug reactions (ADRs) during or after
      administration of octagam(r) 10%, with a particular focus on thromboembolic
      events (TEEs). ADRs were analysed at the case and event level. RESULTS: In this
      analysis of 112 patients receiving octagam(r) 10% (mean dose 0.4 g/kg/infusion),
      there were five cases with at least one adverse drug reaction (ADR) associated
      with 626 infusions of octagam(r) 10% (case incidence of 0.8% per infusion). ADRs
      were of mild or moderate severity. There were a total of 10 events, most commonly
      back pain (n = 3) and headache (n = 2). Nausea, dizziness and a sensation of
      heaviness were also reported. The remaining two events involved drug exposure
      during pregnancy. There were no TEEs or other serious ADRs. DISCUSSION: In this
      subgroup analysis of patients who received octagam(r) 10% (manufactured using an
      amended process) in two PASS studies, the overall ADR rate was low, with ADRs
      occurring in only 0.8% of all infusions. No TEEs or other serious ADRs were
      reported. CONCLUSIONS: Routine clinical use of octagam(r) 10% was safe and well
      tolerated, with no unexpected safety issues, in patients with ITP. The two
      studies from which data were taken are registered with the International Standard
      Randomised Controlled Trial Number Registry, numbers ISRCTN58800347 and
      ISRCTN02245668.

PMID- 29020874
TI  - Safety of corticosteroid injection for carpal tunnel syndrome.
AB  - : The risks of corticosteroid injection for carpal tunnel syndrome, principally
      intraneural injection and tendon rupture, are known only from anecdotal reports.
      The literature does not allow an accurate estimate of their incidence or that of
      lesser side effects such as local pain. We have encountered only four serious
      complications in 9515 injections. We asked patients about possible side effects
      at routine follow-up, 6 weeks after 689 injections with 40 mg triamcinolone.
      Possible side effects were reported after 33% of injections. The commonest was
      short-lived local pain, which occurred in 13% of injected limbs, all cases having
      resolved within 3 weeks. No cases of intraneural injection or tendon rupture
      occurred, even after repeated injection. Most adverse effects were transient, but
      13 hands exhibited persistent skin depigmentation or subcutaneous atrophy. This
      data provides the best current estimate of the risks of carpal tunnel injection
      and may be used to inform patients considering this intervention. LEVEL OF
      EVIDENCE: IV.

PMID- 29020875
TI  - Founder Effect of the RETC611Y Mutation in Multiple Endocrine Neoplasia 2A in
      Denmark: A Nationwide Study.
AB  - BACKGROUND: Multiple endocrine neoplasia (MEN) 2A and 2B are caused by REarranged
      during Transfection (RET) germline mutations. In a recent nationwide study, an
      unusually high prevalence (33%) of families with the C611Y mutation was reported,
      and it was hypothesized that this might be due to a founder effect. The first
      nationwide study of haplotypes in MEN2A families was conducted, with the aim of
      investigating the relatedness and occurrence of de novo mutations among Danish
      families carrying similar mutations. METHODS: The study included 21 apparently
      unrelated MEN2A families identified from a nationwide Danish RET cohort from 1994
      to 2014. Twelve, two, two, three, and two families carried the C611Y, C618F,
      C618Y, C620R, and C634R mutations, respectively. Single nucleotide polymorphism
      chip data and identity by descent analysis were used to assess relatedness.
      RESULTS: A common founder mutation was found among all 12 C611Y families and
      between both C618Y families. No relatedness was identified in the remaining
      families. CONCLUSION: The data suggest that all families with the C611Y germline
      mutation in Denmark originate from a recent common ancestor, probably explaining
      the unusually high prevalence of this mutation. Additionally, the results
      indicate that the C611Y mutation rarely arises de novo, thus underlining the need
      for thorough multigenerational genetic work up in carriers of this mutation.

PMID- 29020876
TI  - Screening for Colorectal Cancer at the Worksite.
AB  - Colorectal cancer (CRC) is the second leading cause of cancer-related deaths
      among men and women in the United States. To increase statewide CRC screening
      rates, the Alabama Department of Public Health (through a Centers for Disease
      Control and Prevention [CDC] Colorectal Cancer Control Program grant) partnered
      with The University of Alabama in Huntsville (UAH) and The University of South
      Alabama (USA) to provide free CRC screening opportunities to eligible University
      employees and dependents. Resources were invested at both universities to ensure
      participant education, tracking, and monitoring. In total, 86 fecal
      immunochemical tests (FITs) were distributed at the UAH campus and 62 were
      returned for testing; 146 FITs were distributed on the USA campus with 111
      returned. Fecal immunochemical test return rates were over 70% at each site. Most
      notably, 21 positive FITs were identified among UAH participants and 25 at USA.
      Findings from both efforts suggest that employer-based screening initiatives are
      a systematic and replicable means of improving CRC screening.

PMID- 29020877
TI  - Discovery of the feline fur-mite Lynxacarus radovskyi in a cat resident in New
      Zealand.

PMID- 29020878
TI  - Pharmacokinetics of articaine hydrochloride and its metabolite articainic acid
      after subcutaneous administration in red deer (Cervus elaphus).
AB  - AIM: To develop and validate a simple and sensitive method using liquid
      chromatography-mass spectrometry (LC-MS) for quantification of articaine, and its
      major metabolite articainic acid, in plasma of red deer (Cervus elaphus), and to
      investigate the pharmacokinetics of articaine hydrochloride and articainic acid
      in red deer following S/C administration of articaine hydrochloride as a complete
      ring block around the antler pedicle. METHODS: The LC-MS method was validated by
      determining linearity, sensitivity, recovery, carry-over and repeatability.
      Articaine hydrochloride (40 mg/mL) was administered S/C to six healthy male red
      deer, at a dose of 1 mL/cm of pedicle circumference, as a complete ring block
      around the base of each antler. Blood samples were collected at various times
      over the following 12 hours. Concentrations in plasma of articaine and articainic
      acid were quantified using the validated LC-MS method. Pharmacokinetic parameters
      of articaine and articainic acid were estimated using non-compartmental analysis.
      RESULTS: Calibration curves were linear for both articaine and articainic acid.
      The limits of quantifications for articaine and articainic acid were 5 and 10
      ng/mL, respectively. Extraction recoveries were >72% for articaine and >68% for
      articainic acid. After S/C administration as a ring block around the base of each
      antler, mean maximum concentrations in plasma (Cmax) of articaine were 1,013.9
      (SD 510.1) ng/mL, detected at 0.17 (SD 0.00) hours, and the Cmax for articainic
      acid was 762.6 (SD 95.4) ng/mL at 0.50 (SD 0.00) hours. The elimination half
      lives of articaine hydrochloride and articainic acid were 1.12 (SD 0.17) and 0.90
      (SD 0.07) hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The LC-MS
      method used for the quantification of articaine and its metabolite articainic
      acid in the plasma of red deer was simple, accurate and sensitive. Articaine
      hydrochloride was rapidly absorbed, hydrolysed to its inactive metabolite
      articainic acid, and eliminated following S/C administration as a ring block in
      red deer. These favourable pharmacokinetic properties suggest that articaine
      hydrochloride should be tested for efficacy as a local anaesthetic in red deer
      for removal of velvet antlers. Further studies to evaluate the safety and
      residues of articaine hydrochloride and articainic acid are required before
      articaine can be recommended for use as a local anaesthetic for this purpose.

PMID- 29020879
TI  - Immunohistochemical and quantitative RT-PCR methods to assess RANK expression in
      normal and neoplastic canine mammary gland.
AB  - The receptor activator of nuclear factor-kB ( RANK) gene is found in both human
      and murine mammary epithelial cells and in human cancer cell lines. We analyzed
      RANK expression in normal and proliferative canine mammary tissue samples ( n =
      47) and cell lines ( n = 10), and identified its expression in epithelial cell
      populations. The correlation of RANK protein with clinicopathologic parameters
      was also studied. A double immunohistochemical method using RANK and p63
      antibodies was applied to 33 tissue samples to analyze RANK protein expression
      and its possible co-expression with p63 protein, the latter used to identify
      myoepithelial (ME) cells (p63-positive) or luminal epithelial (LE) cells (p63
      negative). RANK protein expression was found in ~75% of the tissue samples
      analyzed, at a similar level in all of the histologic types studied: dysplasias
      (4 of 4, 100%), malignant tumors (13 of 17, 76%), normal glands (12 of 17, 70%),
      and benign tumors (6 of 9, 67%). ME and LE cells expressed RANK protein at a
      similar level. A higher level of RANK protein expression was found in older
      animals (>=10 y, p = 0.027). Quantitative RT-PCR was applied to 6 ME (1 normal
      and 5 neoplastic) and 4 LE (1 normal and 3 neoplastic) primary cell lines. The
      RANK gene was found at similar expression levels in all canine mammary ME and LE
      cell lines studied. We found RANK expression in normal, dysplastic, and
      neoplastic canine mammary tissues and cell lines, in both ME and LE cell
      populations.

PMID- 29020881
TI  - Knockdown of REGgamma inhibits the proliferation and migration and promotes the
      apoptosis of multiple myeloma cells by downregulating NF-kappaB signal pathway.
AB  - OBJECTIVES: This study aimed to evaluate the effects of REGgamma knockdown on the
      proliferation, apoptosis and migration of multiple myeloma (MM) cells, and reveal
      the potential regulatory mechanisms. METHODS: The expression of REGgamma on
      myeloma cells of 28 MM patients was detected by Western blot. shRNA-REGgamma-1
      and shRNA-REGgamma-2 were constructed to downregulate REGgamma in RPMI-8226
      cells. The proliferation, apoptosis and migration of transfected cells were
      analyzed by Cell Counting Kit 8 (CCK8), flow cytometry and transwell chamber,
      respectively. The expression of phosphorylated p65 (p-p65), p65, NF-kappa-B
      inhibitor epsilon (IkBepsilon), matrix metalloproteinase 2 (MMP2), B-cell
      lymphoma xL (Bcl-xL) and X-linked inhibitor of apoptosis protein (XIAP) in
      transfected cells was detected by Western blot. Using cycloheximide (CHX), the
      half-life period of IkBepsilon was detected by Western blot. RESULTS: The
      expression of REGgamma was positive in myeloma cells. The proliferation and
      migration of RPMI-8226 cells were significantly inhibited by shRNA-REGgamma
      1/shRNA-REGgamma-2, while the apoptosis rates were significantly increased (p <
      0.05). The expression of p-p65 and IkBepsilon was significantly reduced in RPMI
      8226 cells transfected with shRNA-REGgamma-1/shRNA-REGgamma-2. The degradation of
      IkBepsilon was significantly lower in RPMI-8226 cells transfected with shRNA
      REGgamma-1 than the control (longer half-life period). Besides, the expression of
      MMP2, Bcl-xL and XIAP in RPMI-8226 cells was significantly inhibited by shRNA
      REGgamma-1/shRNA-REGgamma-2. DISCUSSION: Knockdown of REGgamma may inhibit the
      proliferation and migration, and promote the apoptosis of RPMI-8226 cells
      possibly by downregulating NF-kappaB signal pathway.

PMID- 29020882
TI  - Quality of time spent without symptoms of disease or toxicity of treatment for
      transmetatarsal amputation versus digital amputation in diabetic patients with
      digital gangrene.
AB  - Aim We aim to compare the outcome of diabetic patients with gangrenous toes who
      were managed initially either by digital amputation or by transmetatarsal
      amputation. The null hypothesis is that transmetatarsal amputation had less
      theatre trips and better healing. Materials and Methods A parallel observational
      comparative study of all diabetic patients who underwent either digital or
      transmetatarsal amputation in a tertiary referral center from 2002 through 2015.
      Comorbid conditions, subsequent amputations, hospital stay, and readmission were
      noted. Results A total of 223 patients underwent minor amputation during the
      study period, of which 147 patients were diabetic and 76 patients were non
      diabetic. Seventy-seven patients had digital amputation and 70 transmetatarsal
      amputation in diabetic patients. Demographics were similar in both groups. The
      median time to major amputation was (400 +/- IQR 1205 days) in the digital
      amputation group, compared to 690 +/- IQR 891 days in the transmetatarsal
      amputation group ( P = 0.974). 29.9% of digital amputations and 15.7% of
      transmetatarsal amputations in diabetic patients, required minor amputations or
      revision procedures ( P = 0.04). Median length of hospital stay was (20 days, IQR
      27) in the digital group and (17 days, IQR17) in the transmetatarsal amputation
      group ( P = 0.17). Need for re-admission was 48.1% in digital patients compared
      to 50% in transmetatarsal amputation patients ( P = 0.81). Quality of time spent
      without symptoms of disease or toxicity of treatment (Q-TWiST) was (315 days, IQR
      45) in digital group and (346 days, IQR 48) in the transmetatarsal amputation
      patients ( P = 0.099). Conclusion Despite the lack of statistical significance,
      transmetatarsal amputation offered better outcome in the diabetic patients, with
      less re-intervention rate, shorter hospital stays, less theatre trips, and longer
      time without toxicity (TWiST).

PMID- 29020880
TI  - Pulsed Electromagnetic Fields and Tissue Engineering of the Joints.
AB  - BACKGROUND: Bone and joint formation, maintenance, and regeneration are regulated
      by both chemical and physical signals. Among the physical signals there is an
      increasing realization of the role of pulsed electromagnetic fields (PEMF) in the
      treatment of nonunions of bone fractures. The discovery of the piezoelectric
      properties of bone by Fukada and Yasuda in 1953 in Japan established the
      foundation of this field. Pioneering research by Bassett and Brighton and their
      teams resulted in the approval by the Food and Drug Administration (FDA) of the
      use of PEMF in the treatment of fracture healing. Although PEMF has potential
      applications in joint regeneration in osteoarthritis (OA), this evolving field is
      still in its infancy and offers novel opportunities. METHODS: We have
      systematically reviewed the literature on the influence of PEMF in joints,
      including articular cartilage, tendons, and ligaments, of publications from 2000
      to 2016. CONCLUSIONS: PEMF stimulated chondrocyte proliferation, differentiation,
      and extracellular matrix synthesis by release of anabolic morphogens such as bone
      morphogenetic proteins and anti-inflammatory cytokines by adenosine receptors A2A
      and A3 in both in vitro and in vivo investigations. It is noteworthy that in
      clinical translational investigations a beneficial effect was observed on
      improving function in OA knees. However, additional systematic studies on the
      mechanisms of action of PEMF on joints and tissues therein, articular cartilage,
      tendons, and ligaments are required.

PMID- 29020883
TI  - The immune response in trichloroethylene hypersensitivity syndrome: A review.
AB  - Trichloroethylene (TCE) has been used for a variety of industrial and consumer
      cleaning purposes because of its ability to dissolve organic substances. The
      multisystem injuries include those of skin, liver, and kidney, which are defined
      as TCE hypersensitivity syndrome (THS). THS is a serious occupational health
      issue. However, the mechanism of immune dysfunction leading to organ injury is
      poorly understood. Many studies reveal that skin lesions and organ injury caused
      by TCE are consistent with type IV hypersensitivity, also called delayed
      hypersensitivity, mediated by T cells. However, many researchers found T cell
      mediated type IV hypersensitivity could not account for the pathogenesis of THS
      fully. Humoral immunity, including immunoglobulins and complement activation, may
      also play a possible role in THS pathogenesis. This review will describe the
      history, current understanding, and future research directions of the mechanism
      of THS.

PMID- 29020884
TI  - Pathologic Reporting of Tall-Cell Variant of Papillary Thyroid Cancer: Have We
      Reached a Consensus?
AB  - BACKGROUND: Tall-cell variant (TCV) is widely believed to be a more aggressive
      subtype of papillary thyroid carcinoma (PTC). Despite the significance of TCV
      with respect to risk stratification and therapeutic decision making, its
      diagnosis is subject to inter-observer variability. This study aimed to determine
      the level of agreement among expert pathologists in the identification and
      reporting of TCV. METHODS: Seventeen surgical resections for thyroid cancer
      containing the diagnostic term "tall cell" in their pathology reports and 22
      cases diagnosed as classical PTC were selected. Cases were digitalized, and 14
      expert pathologists reviewed the scanned slides blinded to the original
      interpretation. Each pathologist designated each case as TCV or not and answered
      multiple questions about diagnostic histopathologic features of TCV. RESULTS: The
      overall strength of agreement for identifying TCV was fair (Fleiss kappa 0.34),
      and the proportion of observed agreement was 0.70. Of 22 cases originally
      diagnosed as PTC classical variant, 15 (68%) were reclassified as TCV by at least
      one expert pathologist. It was noted that four different definitions for TCV were
      used by the participants based on various combinations of cell height to width
      (H:W) ratio and the percentage of tumor cells showing that specific ratio. All
      pathologists agreed that the diagnosis of TCV does not rely solely on a specific
      H:W ratio. CONCLUSIONS: Pathologic reporting of TCV varies among pathologists.
      This disagreement is a result of the lack of unanimous diagnostic criteria and
      variation in individual pathologists' interpretations. These discrepancies lead
      to over- and under-diagnosis of TCV, which has significant implications in
      patient management. It is imperative to understand this variability in diagnosis
      TCV as it relates to risk stratification and interpretation of clinical studies
      related to this histologic subtype of PTC. Further studies are needed to reach
      consensus on the diagnostic criteria of TCV.

PMID- 29020885
TI  - Identification of PA28beta as a potential novel biomarker in human esophageal
      squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most common and serious
      malignancies in China. However, the exact mechanisms of tumor formation and
      progression are unclear. As late diagnosis and poor therapeutic efficacy result
      in lower survival rates, identifying biomarkers for early detection, prognostic
      evaluation, and recurrence monitoring of ESCC is necessary. Here we analyzed 10
      protein expression profiles of ESCC core tissues and paired normal esophageal
      epithelial tissues using two-dimensional gel electrophoresis. We excised 29
      protein spots with two-fold or greater differential expression between cancer and
      normal tissues and identified them using matrix-assisted laser
      desorption/ionization-time-of-flight/time-of-flight mass spectrometry. The role
      of PA28beta in ESCC cell was confirmed using cell growth, colony formation and
      soft agar in TE-1 cells pre- and post- PA28beta transfection. Compared to their
      expression in the adjacent normal epithelia, 12 proteins, including transgelin
      (TAGLN), were upregulated in ESCC tissues; 17 proteins, including proteasome
      activator 28-beta subunit (PA28beta), were downregulated (p < 0.05). Western
      blotting and immunohistochemistry confirmed that PA28beta was significantly
      underexpressed in ESCC tissues. The functional assays demonstrate that PA28beta
      inhibited cell growth, proliferation and malignancy of TE-1 cells. Among the
      differentially expressed proteins, PA28beta is a potential tumor inhibitor.

PMID- 29020886
TI  - Comparison of culture methodology for the detection of methicillin-resistant
      Staphylococcus pseudintermedius in clinical specimens collected from dogs.
AB  - Methicillin-resistant Staphylococcus pseudintermedius (MRSP) has emerged as a
      major pathogen in dogs and has been implicated as a hospital-acquired pathogen in
      veterinary hospitals. We attempted to determine if selective culture methods will
      detect more MRSP when compared to the traditional culture methods in clinical
      samples from dogs in Atlantic Canada with a high risk for MRSP infection. Each
      sample was tested using 4 culture methods: traditional culture; mannitol salt
      agar with 2 MUg/mL of oxacillin (MSAox); enrichment broth (EB) with MSAox; and EB
      with traditional culture. Detection of penicillin-binding protein 2', via latex
      agglutination, was used as a confirmatory test for oxacillin resistance. We
      analyzed 741 samples from 556 dogs between February 2013 and April 2014. The
      prevalence of MRSP in samples detected by any method was estimated at 13.4% (95%
      CI: 11.1-16.0%). When the prevalence of MRSP was determined according to culture
      method, EB with MSAox detected the highest prevalence (11.2% [9.1-13.7%]),
      followed by EB with traditional (10.8% [8.8-13.2%]), traditional (10.1% [8.1
      12.5%]), and MSAox (8.9% [7.1-11.2%]). The prevalence using the traditional
      culture method did not differ significantly from any of the 3 selective culture
      methods. Culture with MSAox detected significantly fewer MRSP than either of the
      EB methods. The addition of EB to current methodology is recommended,
      particularly for patients considered at high risk for MRSP infection.

PMID- 29020887
TI  - The potential association of tumor necrosis factor-betaeta (252 G/A) cytokine
      gene polymorphism with immune thrombocytopenic purpura among Egyptian children.
AB  - OBJECTIVES: The main objective of this study was to study tumor necrosis factor
      beta (TNFB) + 252G/A gene polymorphism, known to be related to autoimmunity, in
      immune thrombocytopenia (ITP) patients. We also aimed to investigate the
      association between TNFB + 252G/A polymorphism and susceptibility to develop
      persistent/chronic ITP. METHODS: One hundred pediatric ITP patients, as well as
      50 age- and sex-matched healthy Egyptian subjects, were included. Genotyping of
      TNF-beta gene (G252A) was done using the PCR-RFLP method. RESULTS: TNFB allele B2
      frequency was (64%, 64/100) in controls, (69%, 138/200) in ITP patients, while
      the frequency of the variant allele B1 was 36% (36/100) in controls, (31%,
      62/200) in ITP patients. TNFB genotype frequency in ITP patients showed equal
      frequency for B2B2 and B1B2 genotypes, (46%, 46/100), while B1B1 frequency was 8%
      (8/100). Among controls, frequencies of B2B2, B1B2 and B1B1 genotypes were 36%
      (18/50), 56% (28/50), and 8% (4/50), respectively. Odds ratio for the risk of
      developing ITP revealed no statistically significant risk, associated with any
      allele or genotype. No association was encountered between different genotypes
      and age, hematological parameters, gender, stage of the disease or response to
      treatment. DISCUSSION: Comparison between ITP patients and controls as regards
      TNFB allele and genotype frequencies showed no statistically significant
      difference. No increased risk for developing ITP was associated with any
      allele/genotype. CONCLUSION: The risk of developing ITP was not related to the
      studied polymorphism.

PMID- 29020888
TI  - Clinical haematology and biochemistry profiles of cattle naturally infected with
      Theileria orientalis Ikeda type in New Zealand.
AB  - AIMS: To present the haematology and biochemistry profiles for cattle in New
      Zealand naturally infected with Theileria orientalis Ikeda type and investigate
      if the results differed between adult dairy cattle and calves aged <6 months.
      METHODS: Haematology and biochemistry results were obtained from blood samples
      from cattle which tested positive for T. orientalis Ikeda type by PCR, that were
      submitted to veterinary laboratories in New Zealand between October 2012 and
      November 2014. Data sets for haematology and biochemistry results were prepared
      for adult dairy cattle (n=62 and 28, respectively) and calves aged <6 months
      (n=62 and 28, respectively), which were matched on the basis of individual
      haematocrit (HCT). Results were compared between age groups when categorised by
      HCT. Selected variables were plotted against individual HCT, and locally weighted
      scatterplot smoothing (Loess) curves were fitted to the data for adult dairy
      cattle and calves <6 months old. RESULTS: When categorised by HCT, the proportion
      of samples with HCT <0.15 L/L (severe anaemia) was greater for adult dairy cattle
      than for beef or dairy calves, for both haematology (p<0.002) and biochemistry
      (p<0.001) submissions. There were differences (p<0.05) between adult dairy cattle
      and calves aged <6 months in the relationships between HCT and red blood cell
      counts, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular
      haemoglobin concentrations, lymphocyte and eosinophil counts, and activities of
      glutamate dehydrogenase and aspartate aminotransferase. In both age groups
      anisocytosis was frequently recorded. The proportion of blood smears showing mild
      and moderate macrocytosis was greater in adults than calves (p=0.01), and mild
      and moderate poikilocytosis was greater in calves than adults (p=0.005).
      CONCLUSIONS AND CLINICAL RELEVANCE: The haematology and biochemistry changes
      observed in cattle infected with T. orientalis Ikeda type were consistent with
      extravascular haemolytic anaemia. Adult dairy cattle were more likely to be
      severely anaemic than calves. There were differences in haematology and
      biochemistry profiles between adult dairy cattle and calves, but most of these
      differences likely had a physiological rather than pathological basis. Overall,
      the haematological changes in calves aged <6 months appeared less severe than in
      adult dairy cattle.

PMID- 29020889
TI  - Differential Effect of Acute Iron Overload on Oxidative Status and Antioxidant
      Content in Regions of Rat Brain.
AB  - The hypothesis of this study is that the cerebral cortex, hippocampus, and
      striatum of the rat brain are differentially affected in terms of oxidative
      stress and antioxidant capacity by acute Fe overload because Fe is distributed in
      a heterogeneous fashion among different regions and cells of the brain. The
      effects on the lipophilic and hydrophilic cellular environment were compared
      between regions and with the whole brain. A single dose of Fe-dextran increased
      Fe deposits, reaching a maximum after 6 hr. Both in whole brain and in cortex
      region, the ascorbyl/ascorbate content ratio was increased after 6 hr of Fe
      administration, while in striatum and hippocampus, there was no significant
      changes after Fe overload. Total thiol content decreased in whole brain and
      cortex, while there were no significant changes in striatum and hippocampus after
      Fe overload. The content of alpha-tocopherol (alpha-T), whether measured in the
      whole brain or in the isolated regions, did not change following Fe treatment.
      Lipid radical (LR*) generation rate after Fe-dextran overload only increased in
      the cortex region. The LR*/alpha-T content ratio was increased by Fe treatment in
      cortex but not in the whole brain, striatum, or hippocampus, in agreement with
      the study tested hypothesis.

PMID- 29020890
TI  - Career Transition Points in Toxicologic Pathology: Management and Consulting.
AB  - In the constantly evolving field of toxicologic pathology, a pathologist's career
      is often characterized by multiple career transitions. However, these transitions
      can be challenging and/or overwhelming and may require a shift in focus,
      strategic approach, and acquisition of new skills and expertise. In order to
      provide a forum to discuss challenges associated with career transitions and
      skill set/competencies required to navigate career changes effectively and
      successfully, the Career Development and Outreach Committee of the Society of
      Toxicologic Pathology (STP) sponsored a career development workshop entitled
      "Transitions in a Pathologist's Career" in conjunction with the STP 36th annual
      symposium. The presentations at this workshop provided perspectives of managers
      from pharmaceutical companies and Contract Research Organizations as well as
      consultants. This article is designed to provide brief summaries of their talks
      in this well-received career development workshop.

PMID- 29020891
TI  - Biologic Joint Repair Strategies: The Mizzou BioJoint Story.
AB  - Because articular cartilage has very limited healing potential, most symptomatic
      cartilage injuries eventually result in end-stage osteoarthritis and are treated
      with artificial joint replacement. Our interdisciplinary, comparative orthopedic
      research performed by a team of DVMs, MDs, engineers, and basic scientists has
      yielded marked progress toward effective biologic joint restoration strategies by
      bringing bench-side ideas to fruition in bedside applications in both canine and
      human patients. This mini-review summarizes the progress of biologic joint
      restoration strategies at our center.

PMID- 29020893
TI  - Clinical practice guidelines for the diagnosis and management of melanoma:
      melanomas that lack classical clinical features.
AB  - INTRODUCTION: A Cancer Council Australia multidisciplinary working group is
      currently revising and updating the 2008 evidence-based clinical practice
      guidelines for the management of cutaneous melanoma. While there have been many
      recent improvements in treatment options for metastatic melanoma, early diagnosis
      remains critical to reducing mortality from the disease. Improved awareness of
      the atypical presentations of this common malignancy is required to achieve this.
      A chapter of the new guidelines was therefore developed to aid recognition of
      atypical melanomas. Main recommendations: Because thick, life-threatening
      melanomas may lack the more classical ABCD (asymmetry, border irregularity,
      colour variegation, diameter > 6 mm) features of melanoma, a thorough history of
      the lesion with regard to change in morphology and growth over time is essential.
      Any lesion that is changing in morphology or growing over a period of more than
      one month should be excised or referred for prompt expert opinion. Changes in
      management as a result of the guidelines: These guidelines provide greater
      emphasis on improved recognition of the atypical presentations of melanoma, in
      particular nodular, desmoplastic and acral lentiginous subtypes, with particular
      awareness of hypomelanotic and amelanotic lesions.

PMID- 29020895
TI  - The rationale for action to end new cases of rheumatic heart disease in
      Australia.

PMID- 29020892
TI  - Are Evidence-Based Guidelines Reflected in Clinical Practice? An Analysis of
      Prospectively Collected Data of the Italian Thyroid Cancer Observatory.
AB  - OBJECTIVES: The goal of evidence-based practice guidelines is to optimize the
      management of emerging diseases, such as differentiated thyroid cancer (DTC). The
      aim of this study was to assess therapeutic approaches for DTC in Italy and to
      see how closely these practices conformed to those recommended in the 2009
      American Thyroid Association (ATA) guidelines. METHODS: The Italian Thyroid
      Cancer Observatory was established to collect data prospectively on thyroid
      cancers consecutively diagnosed in participating centers (uniformly distributed
      across the nation). Data on the initial treatment of all pathologically confirmed
      DTC cases present in the database from January 1, 2013 (database creation) to
      January 31, 2016, were analyzed. RESULTS: A total of 1748 patients (77.2%
      females; median age 48.1 years [range 10-85 years]) were enrolled in the study.
      Most (n = 1640; 93.8%) were papillary carcinomas (including 84 poorly
      differentiated/aggressive variants); 6.2% (n = 108) were follicular and Hurthle
      cell carcinomas. The median tumor diameter was 11 mm (range 1-93 mm). Tumors were
      multifocal in 613 (35%) and presented extrathyroidal extension in 492 (28%)
      cases. Initial treatments included total thyroidectomy (involving one or two
      procedures; n = 726; 98.8%) and lobectomy (n = 22; 1.2%). A quarter of the
      patients who underwent total thyroidectomy had unifocal, intrathyroidal tumors
      <=1 cm (n = 408; 23.6%). Neck dissection was performed in 40.4% of the patients
      (29.5% had central compartment dissection). Radioiodine remnant ablation (RRA)
      was performed in 1057 (61.2%) of the 1726 patients who underwent total
      thyroidectomy: 460 (41.2%) of the 983 classified by 2009 ATA guideline criteria
      as low-risk, 570 (87.1%) of the 655 as intermediate-risk, and 82 (93.1%) of the
      88 as high-risk patients (p < 0.001). RRA was performed in 44% of the cases
      involving multifocal DTCs measuring <=1 cm. CONCLUSIONS: The treatment approaches
      for DTCs used in Italy display areas of inconsistency with those recommended by
      the 2009 ATA guidelines. Italian practices were characterized by underuse of
      thyroid lobectomy in intrathyroidal, unifocal DTCs <=1 cm. The use of RRA was
      generally consistent with risk-stratified recommendations. However, its frequent
      use in small DTCs (<=1 cm) that are multifocal persists, despite the lack of
      evidence of benefit. These data provide a baseline for future assessments of the
      impact of international guidelines on DTC management in Italy. These findings
      also illustrate that the dissemination and implementation of guideline
      recommendations, and the change in practice patterns, require ongoing education
      and time.

PMID- 29020896
TI  - Neonatal tinea corporis.

PMID- 29020897
TI  - Recognising severe cutaneous adverse drug reactions.

PMID- 29020898
TI  - Livedo racemosa.

PMID- 29020899
TI  - Polymorphic light eruption.

PMID- 29020900
TI  - Phytophotodermatitis from lime juice.

PMID- 29020901
TI  - Dissecting clinical communication.

PMID- 29020902
TI  - Whither melanoma in Australia?

PMID- 29020903
TI  - Explaining the high prevalence of young-onset diabetes among Asians and
      Indigenous Australians.

PMID- 29020904
TI  - Nodular melanoma is less likely than superficial spreading melanoma to be
      histologically associated with a naevus.
AB  - OBJECTIVES: To determine the frequency of naevus-associated melanoma among
      superficial spreading and nodular subtypes; and to investigate associations
      between naevus-associated melanoma and other clinico-pathological
      characteristics. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of all
      patients with nodular and superficial spreading melanomas diagnosed between 1994
      and 2015 at the Victorian Melanoma Service, Melbourne. METHODS AND MAIN OUTCOME
      MEASURES: Clinical and pathological characteristics of naevus-associated and de
      novo melanomas were assessed in univariable and multivariable logistic regression
      analyses. RESULTS: Of 3678 primary melanomas, 1360 (37.0%) were histologically
      associated with a naevus and 2318 (63.0%) were de novo melanomas; 71 of 621
      nodular (11.4%) and 1289 of 3057 superficial spreading melanomas (42.2%) were
      histologically associated with a naevus. In multivariable analyses, the odds of
      being associated with a naevus were higher for melanomas located on the trunk (v
      head and neck: adjusted odds ratio [OR], 2.27; 95% CI, 1.73-2.96; P < 0.001),
      while the odds were lower for thicker tumours (adjusted OR, 0.75 per millimetre
      increase in Breslow thickness; 95% CI, 0.69-0.81; P < 0.001),
      amelanotic/hypomelanotic melanomas (adjusted OR, 0.68; 95% CI, 0.48-0.97; P =
      0.035), and older age (patients 70 years or older v patients under 30 at
      diagnosis: adjusted OR, 0.28; 95% CI, 0.20-0.40; P < 0.001). After adjusting for
      confounders, the odds of an associated naevus was three times as high for
      superficial spreading melanomas as for nodular melanomas (adjusted OR, 3.05; 95%
      CI, 2.24-4.17; P < 0.001). CONCLUSION: Melanomas are most likely to arise in the
      absence of a pre-existing naevus, particularly nodular melanomas. Public health
      campaigns should therefore emphasise the detection of suspicious de novo lesions,
      as well as of changing lesions.

PMID- 29020905
TI  - The incidence and multiplicity rates of keratinocyte cancers in Australia.
AB  - OBJECTIVES: To assess the incidence and multiplicity of keratinocyte cancers
      (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]) excised in
      Australia, and to examine variations by age, sex, state, and prior skin cancer
      history. DESIGN: Analysis of individual-level Medicare data for keratinocyte
      cancer treatments (identified by eight specific MBS item codes) during 2011-2014.
      Histological data from the QSkin prospective cohort study were analysed to
      estimate BCC and SCC incidence. SETTING: A 10% systematic random sample of all
      people registered with Medicare during 1997-2014. PARTICIPANTS: People aged at
      least 20 years in 2011 who made at least one claim for any MBS medical service
      during 2011-2014 (1 704 193 individuals). MAIN OUTCOME MEASURES: Age-standardised
      incidence rates (ASRs) and standardised incidence ratios (SIRs). RESULTS: The
      person-based incidence of keratinocyte cancer excisions in Australia was 1531 per
      100 000 person-years; incidence increased with age, and was higher for men than
      women (SIR, 1.43; 95% CI, 1.42-1.45). Lesion-based incidence was 3154 per 100 000
      person-years. The estimated ASRs for BCC and SCC were 770 per 100 000 and 270 per
      100 000 person-years respectively. During 2011-2014, 3.9% of Australians had one
      keratinocyte cancer excised, 2.7% had more than one excised; 74% of skin cancers
      were excised from patients who had two or more lesions removed. Multiplicity was
      strongly correlated with age; most male patients over 70 were treated for
      multiple lesions. Keratinocyte cancer incidence was eight times as high among
      people with a prior history of excisions as among those without. CONCLUSIONS: The
      incidence and multiplicity of keratinocyte cancer in Australia are very high,
      causing a large disease burden that has not previously been quantified.

PMID- 29020906
TI  - The prevalence of monogenic diabetes in Australia: the Fremantle Diabetes Study
      Phase II.
AB  - OBJECTIVE: To determine the prevalence of monogenic diabetes in an Australian
      community. DESIGN: Longitudinal observational study of a cohort recruited between
      2008 and 2011. SETTING: Urban population of 157 000 people (Fremantle, Western
      Australia). PARTICIPANTS: 1668 (of 4639 people with diabetes) who consented to
      participation (36.0% participation). MAIN OUTCOME MEASURES: Prevalence of
      maturity-onset diabetes of the young (MODY) and permanent neonatal diabetes in
      patients under 35 years of age, from European and non-European ethnic
      backgrounds, who were at risk of MODY according to United Kingdom risk prediction
      models, and who were then genotyped for relevant mutations. RESULTS: Twelve of
      148 young participants with European ethnic backgrounds (8%) were identified by
      the risk prediction model as likely to have MODY; four had a glucokinase gene
      mutation. Thirteen of 45 with non-European ethnic backgrounds (28%) were
      identified as likely to have MODY, but none had a relevant mutation (DNA
      unavailable for one patient). Two patients with European ethnic backgrounds (one
      likely to have MODY) had neonatal diabetes. The estimated MODY prevalence among
      participants with diagnosed diabetes was 0.24% (95% confidence interval [CI],
      0.08-0.66%), an overall population prevalence of 89 cases per million; the
      prevalence of permanent neonatal diabetes was 0.12% (95% CI, 0.02-0.48%) and the
      population prevalence 45 cases per million. CONCLUSIONS: One in 280 Australians
      diagnosed with diabetes have a monogenic form; most are of European ethnicity.
      Diagnosing MODY and neonatal diabetes is important because their management
      (including family screening) and prognosis can differ significantly from those
      for types 1 and 2 diabetes.

PMID- 29020907
TI  - Atopic dermatitis: the new frontier.
AB  - Atopic dermatitis (AD) is the most common inflammatory skin condition in adults
      and children. AD is a chronic disease that has a considerable negative impact on
      the quality of life of patients and their families. Most cases of AD may be
      effectively treated with topical therapies that are directed at decreasing
      cutaneous inflammation and alleviating pruritus. These therapies include
      emollients, antihistamines, topical corticosteroids, topical calcineurin
      inhibitors and antimicrobial and antiseptic measures; more refractory cases may
      require additional oral immunosuppression (eg, cyclosporine, azathioprine,
      methotrexate and mycophenolate). Improved understanding of the immune
      pathogenesis of AD, including the role of T helper cells and the inflammatory
      pathways involved, has led to breakthrough translational clinical research and
      treatment. New targeted immunotherapies, such as inhibitors of interleukin (IL)
      4, IL-13, IL-31, Janus associated kinase and phosphodiesterase, have had
      promising results from phase 2 and 3 trials for patients with moderate to severe
      AD.

PMID- 29020909
TI  - Clot retrieval and acute stroke care.

PMID- 29020910
TI  - Clot retrieval and acute stroke care.

PMID- 29020911
TI  - Automated diagnosis of melanoma.

PMID- 29020908
TI  - Cardiac Society of Australia and New Zealand position statement executive
      summary: coronary artery calcium scoring.
AB  - Introduction This article summarises the Cardiac Society of Australia and New
      Zealand position statement on coronary artery calcium (CAC) scoring. CAC scoring
      is a non-invasive method for quantifying coronary artery calcification using
      computed tomography. It is a marker of atherosclerotic plaque burden and the
      strongest independent predictor of future myocardial infarction and mortality.
      CAC scoring provides incremental risk information beyond traditional risk
      calculators such as the Framingham Risk Score. Its use for risk stratification is
      confined to primary prevention of cardiovascular events, and can be considered as
      individualised coronary risk scoring for intermediate risk patients, allowing
      reclassification to low or high risk based on the score. Medical practitioners
      should carefully counsel patients before CAC testing, which should only be
      undertaken if an alteration in therapy, including embarking on pharmacotherapy,
      is being considered based on the test result. Main recommendations CAC scoring
      should primarily be performed on individuals without coronary disease aged 45-75
      years (absolute 5-year cardiovascular risk of 10-15%) who are asymptomatic. CAC
      scoring is also reasonable in lower risk groups (absolute 5-year cardiovascular
      risk, < 10%) where risk scores traditionally underestimate risk (eg, family
      history of premature CVD) and in patients with diabetes aged 40-60 years. We
      recommend aspirin and a high efficacy statin in high risk patients, defined as
      those with a CAC score >= 400, or a CAC score of 100-399 and above the 75th
      percentile for age and sex. It is reasonable to treat patients with CAC scores >=
      100 with aspirin and a statin. It is reasonable not to treat asymptomatic
      patients with a CAC score of zero. Changes in management as a result of this
      statement Cardiovascular risk is reclassified according to CAC score. High risk
      patients are treated with a high efficacy statin and aspirin. Very low risk
      patients (ie, CAC score of zero) do not benefit from treatment.

PMID- 29020912
TI  - Hot water immersion <em>v</em> icepacks for treating pain of <em>Chironex
      fleckeri</em> stings: a randomised controlled trial.

PMID- 29020913
TI  - Hot water immersion <em>v</em> icepacks for treating pain of <em>Chironex
      fleckeri</em> stings: a randomised controlled trial.

PMID- 29020914
TI  - Driving the AMSA agenda.

PMID- 29020915
TI  - Around the universities and research institutes.

PMID- 29020918
TI  - Hox genes reveal genomic DNA variation in tetraploid hybrids derived from
      Carassius auratus red var. (female) * Megalobrama amblycephala (male).
AB  - BACKGROUND: Allotetraploid F1 hybrids (4nF1) (AABB, 4n = 148) were generated from
      the distant hybridization of Carassius auratus red var. (RCC) (AA, 2n = 100) (?)
      * Megalobrama amblycephala (BSB) (BB, 2n = 48) (?). It has been reported that Hox
      gene clusters are highly conserved among plants and vertebrates. In this study,
      we investigated the genomic organization of Hox gene clusters in the
      allotetraploid F1 hybrids and their parents to investigate the polyploidization
      process. RESULTS: There were three copies of Hox genes in the 4nF1 hybrids, two
      copies in RCC and one copy in BSB. In addition, obvious variation and
      pseudogenization were observed in some Hox genes from 4nF1. CONCLUSION: Our
      results reveal the influence of polyploidization on the organization and
      evolution of Hox gene clusters in fish and also clarify some aspects of
      vertebrate genome evolution.

PMID- 29020917
TI  - Deciphering the olfactory repertoire of the tiger mosquito Aedes albopictus.
AB  - BACKGROUND: The Asian tiger mosquito Aedes albopictus is a highly invasive
      species and competent vector of several arboviruses (e.g. dengue, chikungunya,
      Zika) and parasites (e.g. dirofilaria) of public health importance. Compared to
      other mosquito species, Ae. albopictus females exhibit a generalist host seeking
      as well as a very aggressive biting behaviour that are responsible for its high
      degree of nuisance. Several complex mosquito behaviours such as host seeking,
      feeding, mating or oviposition rely on olfactory stimuli that target a range of
      sensory neurons localized mainly on specialized head appendages such as antennae,
      maxillary palps and the mouthparts. RESULTS: With the aim to describe the Ae.
      albopictus olfactory repertoire we have used RNA-seq to reveal the transcriptome
      profiles of female antennae and maxillary palps. Male heads and whole female
      bodies were employed as reference for differential expression analysis. The
      relative transcript abundance within each tissue (TPM, transcripts per kilobase
      per million) and the pairwise differential abundance in the different tissues
      (fold change values and false discovery rates) were evaluated. Contigs
      upregulated in the antennae (620) and maxillary palps (268) were identified and
      relative GO and PFAM enrichment profiles analysed. Chemosensory genes were
      described: overall, 77 odorant binding proteins (OBP), 82 odorant receptors (OR),
      60 ionotropic receptors (IR) and 30 gustatory receptors (GR) were identified by
      comparative genomics and transcriptomics. In addition, orthologs of genes
      expressed in the female/male maxillary palps and/or antennae and involved in
      thermosensation (e.g. pyrexia and arrestin1), mechanosensation (e.g. piezo and
      painless) and neuromodulation were classified. CONCLUSIONS: We provide here the
      first detailed transcriptome of the main Ae. albopictus sensory appendages, i.e.
      antennae and maxillary palps. A deeper knowledge of the olfactory repertoire of
      the tiger mosquito will help to better understand its biology and may pave the
      way to design new attractants/repellents.

PMID- 29020919
TI  - Cell wall metabolism and hexose allocation contribute to biomass accumulation in
      high yielding extreme segregants of a Saccharum interspecific F2 population.
AB  - BACKGROUND: Sugarcane is an emerging dual-purpose biofuel crop for energy and
      sugar production, owing to its rapid growth rate, high sucrose storage in the
      stems, and high lignocellulosic yield. It has the highest biomass production
      reaching 1.9 billion tonnes in 2014 worldwide. RESULTS: To improve sugarcane
      biomass accumulation, we developed an interspecific cross between Saccharum
      officinarum 'LA Purple' and Saccharum robustum 'MOL5829'. Selected F1 individuals
      were self-pollinated to generate a transgressive F2 population with a wide range
      of biomass yield. Leaf and stem internodes of fourteen high biomass and eight low
      biomass F2 extreme segregants were used for RNA-seq to decipher the molecular
      mechanism of rapid plant growth and dry weight accumulation. Gene Ontology terms
      involved in cell wall metabolism and carbohydrate catabolism were enriched among
      3274 differentially expressed genes between high and low biomass groups. Up
      regulation of cellulose metabolism, pectin degradation and lignin biosynthesis
      genes were observed in the high biomass group, in conjunction with higher
      transcript levels of callose metabolic genes and the cell wall loosening enzyme
      expansin. Furthermore, UDP-glucose biosynthesis and sucrose conversion genes were
      differentially expressed between the two groups. A positive correlation between
      stem glucose, but not sucrose, levels and dry weight was detected. CONCLUSIONS:
      We thus postulated that the high biomass sugarcane plants rapidly convert sucrose
      to UDP-glucose, which is the building block of cell wall polymers and callose, in
      order to maintain the rapid plant growth. The gene interaction of cell wall
      metabolism, hexose allocation and cell division contributes to biomass yield.

PMID- 29020920
TI  - First identification of Gordonia sputi in a post-traumatic endophthalmitis
      patient - a case report and literatures review.
AB  - BACKGROUND: We present a case of post-traumatic endophthalmitis with relatively
      good prognosis caused by Gordonia sputi, which, to our knowledge is the first
      case in the literature. CASE PRESENTATION: A 24 year old man, who underwent an
      intraocular foreign body extraction half a month before presentation in the left
      eye, was referred to us complaining of blurred vision and slight pain for 5 days.
      His first presentation showed moderate intracameral and intravitreous purulent
      inflammation with a best corrected vision of counting fingers. After gram
      staining of the intravitreous samples revealed a gram-positive bacilli infection,
      a combination of amikacin and vancomycin was initially injected intravitreously.
      The left eye kept stable for three days but deteriorated on the 4th day. On the
      5th day after presentation conventional culture characterized the bacterium as an
      Actinomyces sp. while 16S ribosomal RNA gene sequencing confirmed it as Gordonia
      sputi. Thereby a complete pars plana vitrectomy combined with lensectomy and
      silicone oil tamponade was performed. During the surgery an intraocular
      irrigation with penicillin G was adopted, followed by administration of
      intravenous penicillin G twice one day for a week. A relatively normal fundus
      with slight intracameral inflammation was observed a week after the operation,
      and the best corrected vision recovered to 0.15. One year later his vision
      remained 0.1. CONCLUSION: Gordonia sputi should be taken into consideration in
      patients with post-traumatic endophthalmitis especially due to foreign body
      penetration. Compared to conventional laboratories, molecular methods are
      recommended for an accurate diagnosis. A comprehensive strategy of antimicrobial
      agents and vitrectomy may render a satisfactory result.

PMID- 29020916
TI  - Integrated analysis of coding genes and non-coding RNAs during hair follicle
      cycle of cashmere goat (Capra hircus).
AB  - BACKGROUND: Cashmere growth is a seasonal and cyclic phenomenon under the control
      of photoperiod and multiple stimulatory and inhibitory signals. Beyond relevant
      coding genes, microRNA (miRNA) and long non coding RNA (lncRNA) play an
      indispensable role in hair follicle (HF) development and skin homeostasis.
      Furthermore, the influence of lncRNA upon miRNA function is also rapidly
      emerging. However, little is known about miRNAs, lncRNAs and their functions as
      well as their interactions on cashmere development and cycling. RESULT: Here,
      based on lncRNA and miRNA high-throughput sequencing and bioinformatics analysis,
      we have identified 1108 lncRNAs and 541 miRNAs in cashmere goat skin during
      anagen and telogen. Compared with telogen, 1388 coding genes, 41 lncRNAs and 15
      miRNAs were upregulated, while 1104 coding genes, 157 lncRNAs and 8 miRNAs were
      downregulated in anagen (adjusted P-value <=0.05 and relative fold-change >=2).
      Subsequently, we investigated the impact of lncRNAs on their target genes in cis
      and trans, indicating that these lncRNAs are functionally conserved during HF
      development and cycling. Furthermore, miRNA-mRNA and miRNA-lncRNA interaction
      were identified through the bioinformatics algorithm miRanda, then the ceRNA
      networks, miR-221-5p-lnc_000679-WNT3, miR-34a-lnc_000181-GATA3 and miR-214-3p
      lnc_000344-SMAD3, were constructed under defined rules, to illustrate their roles
      in cashmere goat HF biology. CONCLUSION: The present study provides a resource
      for lncRNA, miRNA and mRNA studies in cashmere cycling and development. We also
      demonstrate potential ceRNA regulatory networks in cashmere goat HF cycling for
      the first time. It expands our knowledge about lncRNA and miRNA biology as well
      as contributes to the annotation of the goat genome.

PMID- 29020921
TI  - Identify Huntington's disease associated genes based on restricted Boltzmann
      machine with RNA-seq data.
AB  - BACKGROUND: Predicting disease-associated genes is helpful for understanding the
      molecular mechanisms during the disease progression. Since the pathological
      mechanisms of neurodegenerative diseases are very complex, traditional statistic
      based methods are not suitable for identifying key genes related to the disease
      development. Recent studies have shown that the computational models with deep
      structure can learn automatically the features of biological data, which is
      useful for exploring the characteristics of gene expression during the disease
      progression. RESULTS: In this paper, we propose a deep learning approach based on
      the restricted Boltzmann machine to analyze the RNA-seq data of Huntington's
      disease, namely stacked restricted Boltzmann machine (SRBM). According to the
      SRBM, we also design a novel framework to screen the key genes during the
      Huntington's disease development. In this work, we assume that the effects of
      regulatory factors can be captured by the hierarchical structure and narrow
      hidden layers of the SRBM. First, we select disease-associated factors with
      different time period datasets according to the differentially activated neurons
      in hidden layers. Then, we select disease-associated genes according to the
      changes of the gene energy in SRBM at different time periods. CONCLUSIONS: The
      experimental results demonstrate that SRBM can detect the important information
      for differential analysis of time series gene expression datasets. The
      identification accuracy of the disease-associated genes is improved to some
      extent using the novel framework. Moreover, the prediction precision of disease
      associated genes for top ranking genes using SRBM is effectively improved
      compared with that of the state of the art methods.

PMID- 29020922
TI  - A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel
      genes and mutations associated with pyrazinamide resistance.
AB  - BACKGROUND: Tuberculosis (TB) is a major global health problem and drug
      resistance compromises the efforts to control this disease. Pyrazinamide (PZA) is
      an important drug used in both first and second line treatment regimes. However,
      its complete mechanism of action and resistance remains unclear. RESULTS: We
      genotyped and sequenced the complete genomes of 68 M. tuberculosis strains
      isolated from unrelated TB patients in Peru. No clustering pattern of the strains
      was verified based on spoligotyping. We analyzed the association between PZA
      resistance with non-synonymous mutations and specific genes. We found mutations
      in pncA and novel genes significantly associated with PZA resistance in strains
      without pncA mutations. These included genes related to transportation of metal
      ions, pH regulation and immune system evasion. CONCLUSIONS: These results suggest
      potential alternate mechanisms of PZA resistance that have not been found in
      other populations, supporting that the antibacterial activity of PZA may hit
      multiple targets.

PMID- 29020923
TI  - Comparative analysis of miRNA expression during the development of insects of
      different metamorphosis modes and germ-band types.
AB  - BACKGROUND: Do miRNAs contribute to specify the germ-band type and the body
      structure in the insect embryo? Our goal was to address that issue by studying
      the changes in miRNA expression along the ontogeny of the German cockroach
      Blattella germanica, which is a short germ-band and hemimetabolan species.
      RESULTS: We sequenced small RNA libraries representing 11 developmental stages of
      B. germanica ontogeny (with especial emphasis on embryogenesis) and the changes
      in miRNA expression were examined. Data were compared with equivalent data for
      two long germ-band holometabolan species Drosophila melanogaster and Drosophila
      virilis, and the short germ-band holometabolan species Tribolium castaneum. The
      identification of B. germanica embryo small RNA sequences unveiled miRNAs not
      detected in previous studies, such as those of the MIR-309 family and 54 novel
      miRNAs. Four main waves of miRNA expression were recognized (with most miRNA
      changes occurring during the embryonic stages): the first from day 0 to day 1 of
      embryogenesis, the second during mid-embryogenesis (days 0-6), the third (with an
      acute expression peak) on day 2 of embryonic development, and the fourth during
      post-embryonic development. The second wave defined the boundaries of maternal-to
      zygotic transition, with maternal mRNAs being cleared, presumably by Mir-309 and
      associated scavenger miRNAs. CONCLUSION: miRNAs follow well-defined patterns of
      expression over hemimetabolan ontogeny, patterns that are more diverse during
      embryonic development than during the nymphal stages. The results suggest that
      miRNAs play important roles in the developmental transitions between the
      embryonic stages of development (starting with maternal loading), during which
      they might influence the germ-band type and metamorphosis mode.

PMID- 29020925
TI  - VDJPipe: a pipelined tool for pre-processing immune repertoire sequencing data.
AB  - BACKGROUND: Pre-processing of high-throughput sequencing data for immune
      repertoire profiling is essential to insure high quality input for downstream
      analysis. VDJPipe is a flexible, high-performance tool that can perform multiple
      pre-processing tasks with just a single pass over the data files. RESULTS:
      Processing tasks provided by VDJPipe include base composition statistics
      calculation, read quality statistics calculation, quality filtering, homopolymer
      filtering, length and nucleotide filtering, paired-read merging, barcode
      demultiplexing, 5' and 3' PCR primer matching, and duplicate reads collapsing.
      VDJPipe utilizes a pipeline approach whereby multiple processing steps are
      performed in a sequential workflow, with the output of each step passed as input
      to the next step automatically. The workflow is flexible enough to handle the
      complex barcoding schemes used in many immunosequencing experiments. Because
      VDJPipe is designed for computational efficiency, we evaluated this by comparing
      execution times with those of pRESTO, a widely-used pre-processing tool for
      immune repertoire sequencing data. We found that VDJPipe requires <10% of the run
      time required by pRESTO. CONCLUSIONS: VDJPipe is a high-performance tool that is
      optimized for pre-processing large immune repertoire sequencing data sets.

PMID- 29020926
TI  - A comparison of the use of propofol alone and propofol with midazolam for
      pediatric magnetic resonance imaging sedation - a retrospective cohort study.
AB  - BACKGROUND: Pediatric MRI sedation performed by a variety of specialists such as
      sedationists and anesthesiologists commonly uses propofol, which has similar
      effects to an ideal sedative agent for maintaining deep sedation. However, when
      propofol is used, adverse airway events are relatively more common than when
      using other sedative agents. The concomitant administration of midazolam and
      propofol can reduce the dose of propofol needed for adequate sedation and might
      also reduce the frequency of airway obstruction without affecting the patient's
      recovery profile. METHODS: We reviewed the our hospital records of all pediatric
      MRI sedation patients aged 3 to 16 years who were sedated with either propofol
      alone or propofol with midazolam between December 2013 and June 2016. RESULTS:
      Eight hundred ninety-seven pediatric MRI sedation patients were included (n =
      897). The frequency of airway intervention was 25/356 (7.0%) in Group P and
      15/541 (2.8%) in Group PM (difference in proportions: 4.2%; 95% CI: 1.4-7.6%; p =
      0.002). The mean (SD) time to awake was longer in Group PM compared to Group P
      [21.2 (5.6) minutes vs. 23.0 (7.1) minutes; mean difference, 1.8 min; 95% CI, 0.9
      2.9; p < 0.001]. The mean (SD) time to discharge was longer in Group PM compared
      to Group P [34.5 (6.9) minutes vs. 38.6 (9.4) minutes; mean difference, 4.0 min;
      95% CI, 3.0-5.1; p < 0.001]. CONCLUSIONS: The administration of a small dose of
      midazolam during pediatric MRI sedation using propofol can reduce the frequency
      of airway complications without prolonging the clinically significant recovery
      profile.

PMID- 29020927
TI  - Dilemmas in a pregnant woman with myelofibrosis secondary to signet ring
      adenocarcinoma: a case report.
AB  - BACKGROUND: We describe the first reported case of myelofibrosis as an extremely
      rare complication of gastric cancer during pregnancy; the clinical diagnosis and
      treatment of which is highly challenging due to nonspecific symptoms coupled with
      the conflicting needs of immediate disease control and continuation of pregnancy.
      CASE PRESENTATION: We report a 36-year-old pregnant woman who presented with
      cytopenia, fatigue, vomiting, and diarrhea for 20 days on the background of newly
      diagnosed myelofibrosis secondary to gastric signet ring adenocarcinoma. She
      accepted palliative care and died several months after the delivery of a healthy
      newborn. CONCLUSION: Signet ring gastric adenocarcinoma is an unusual cause of
      myelofibrosis during pregnancy. Treatment remains a great challenge as clinicians
      have to consider the needs of immediate treatment against fetal well-being while
      taking into account patient preference and fetus rights.

PMID- 29020928
TI  - G allele at -924 A > G position of FoxP3 gene promoter as a risk factor for
      tuberculosis.
AB  - BACKGROUND: Forkhead box protein 3 (FoxP3) is an important factor for development
      and function of Regulatory T cells (Treg). Studies have found an association
      between common gene polymorphisms in FoxP3 and some infectious diseases. The aim
      of this study was to evaluate possible associations between two Single nucleotide
      polymorphisms (SNPs) in the promoter of the FoxP3 gene to susceptibility to
      tuberculosis (TB) and the alteration of Foxp3 gene expression. METHODS: The
      pattern distribution of genotype at two position, -3279 A > C (rs3761548) and 
      924 A > G (rs2232365) on the promoter of FoxP3 gene was evaluated using
      polymerase chain reaction-single specific primer (PCR-SSP) method in 183
      tuberculosis patients and 183 healthy control. In addition the quantity of FoxP3
      gene expression at mRNA level was identified by the real-time PCR. RESULTS: The
      frequency of G allele at -924 A > G was significantly higher was higher in TB
      patients (59.5%) than control group (39.5%) (P <= 0.05). In addition, our data
      viewed approximately 5- folds more FoxP3 gene expression in female patients with
      GG genotype in comparison to female healthy cases with the same genotype (P <=
      0.001). There was no statistically significant differences between the
      distribution pattern of -3279 A > C polymorphism in patients and healthy
      individuals along with it effect on the FoxP3 gene expression among both groups
      (P > 0.05). CONCLUSIONS: Our outcome suggests that the -924 A > G polymorphism
      leads to enhance FoxP3 gene expression and susceptibility to tuberculosis in the
      sex dependent manner. This event may rise the count of Treg cells and modulate
      the immune response against tuberculosis.

PMID- 29020929
TI  - A scoping review of prevalence, incidence and risk factors for HIV infection
      amongst young people in Brazil.
AB  - BACKGROUND: Despite young people being a key population for HIV prevention, the
      HIV epidemic amongst young Brazilians is perceived to be growing. We therefore
      reviewed all published literature on HIV prevalence and risk factors for HIV
      infection amongst 10-25 year olds in Brazil. METHODS: We searched Embase, LILACS,
      Proquest, PsycINFO, PubMed, Scopus and Web of Science for studies published up to
      March 2017 and analyzed reference lists of relevant studies. We included
      published studies from any time in the HIV epidemic which provided estimates
      specific to ages 10-25 (or some subset of this age range) for Brazilians on
      either: (a) HIV prevalence or incidence; or (b) the association between HIV and
      socio-demographic or behavioral risk factors. RESULTS: Forty eight publications
      met the inclusion criteria: 44 cross-sectional, two case-control, two cohort.
      Four studies analysed national data. Forty seven studies provided HIV prevalence
      estimates, largely for six population subgroups: Counselling and Testing Center
      attendees; blood donors; pregnant women; institutional individuals; men-who-have
      sex-with-men (MSM) and female sex workers (FSW); four provided HIV incidence
      estimates. Twelve studies showed HIV status to be associated with a wide range of
      risk factors, including age, sexual and reproductive history, infection history,
      substance use, geography, marital status, mental health and socioeconomic status.
      CONCLUSIONS: Few published studies have examined HIV amongst young people in
      Brazil, and those published have been largely cross-sectional and focused on
      traditional risk groups and the south of the country. Despite these limitations,
      the literature shows raised HIV prevalence amongst MSM and FSW, as well as
      amongst those using drugs. Time trends are harder to identify, although rates
      appear to be falling for pregnant women, possibly reversing an earlier de
      masculinization of the epidemic. Improved surveillance of HIV incidence,
      prevalence and risk factors is a key component of efforts to eliminate HIV in
      Brazil.

PMID- 29020924
TI  - Plant jasmonate ZIM domain genes: shedding light on structure and expression
      patterns of JAZ gene family in sugarcane.
AB  - BACKGROUND: Sugarcane smut caused by Sporisorium scitamineum is one of the most
      severe fungal diseases in the sugarcane industry. Using a molecular biological
      technique to mine sugarcane resistance genes can provide gene resources for
      further genetic engineering of sugarcane disease-resistant breeding. Jasmonate
      ZIM (zinc-finger inflorescence meristem) domain (JAZ) proteins, which involved in
      the responses to plant pathogens and abiotic stresses, are important signaling
      molecules of the jasmonic acid (JA) pathway. RESULTS: Seven differentially
      expressed sugarcane JAZ genes, ScJAZ1-ScJAZ7, were mined from the transcriptome
      of sugarcane after inoculation with S. scitamineum. Bioinformatic analyses
      revealed that these seven ScJAZ genes encoded basic proteins that contain the
      TIFY and CCT_2 domains. Quantitative reverse transcription polymerase chain
      reaction (qRT-PCR) analysis demonstrated that the ScJAZ1-ScJAZ7 genes were tissue
      specific and differentially expressed under adverse stress. During S. scitamineum
      infection, the transcripts of ScJAZ4 and ScJAZ5 were both upregulated in the
      susceptible genotype ROC22 and the resistant genotype Yacheng05-179; ScJAZ1,
      ScJAZ2, ScJAZ3, and ScJAZ7 were downregulated in Yacheng05-179 and upregulated in
      ROC22; and the expression of ScJAZ6 did not change in ROC22, but was upregulated
      in Yacheng05-179. The transcripts of the seven ScJAZ genes were increased by the
      stimuli of salicylic acid and abscisic acid, particularly methyl jasmonate. The
      expression of the genes ScJAZ1-ScJAZ7 was immediately upregulated by the
      stressors hydrogen peroxide, sodium chloride, and copper chloride, whereas
      slightly induced after treatment with calcium chloride and polyethylene glycol.
      In addition, the expression of ScJAZ6, as well as seven tobacco immunity
      associated marker genes were upregulated, and antimicrobial activity against
      Pseudomonas solanacearum and Fusarium solani var. coeruleum was observed during
      the transient overexpression of ScJAZ6 in Nicotiana benthamiana, suggesting that
      the ScJAZ6 gene is associated with plant immunity. CONCLUSIONS: The different
      expression profiles of the ScJAZ1-ScJAZ7 genes during S. scitamineum infection,
      the positive response of ScJAZ1-ScJAZ7 to hormones and abiotic treatments, and
      the function analysis of the ScJAZ6 gene revealed their involvement in the
      defense against biotic and abiotic stresses. The findings of the present study
      facilitate further research on the ScJAZ gene family especially their regulatory
      mechanism in sugarcane.

PMID- 29020930
TI  - The XRCC 1 DNA repair gene modifies the environmental risk of stomach cancer: a
      hospital-based matched case-control study.
AB  - BACKGROUND: Previous studies have found that polymorphisms of the DNA repair gene
      X-ray repair cross-complementing group 1(XRCC1) and environmental factors are
      both associated with an increased risk of stomach cancer, but no study has
      reported on the potential additive effect of these factors among Thai people. The
      aim of this study was to investigate whether the risk of stomach cancer from
      XRCC1 gene polymorphisms was modified by environmental factors in the Thai
      population. METHODS: Hospital-based matched case-control study data were
      collected from 101 new stomach cancer cases and 202 controls, which were
      recruited from2002 to 2006 and were matched for gender and age. Genotype analysis
      was performed using real-time PCR-HRM. The data were analysed by the chi-square
      test and conditional logistic regression. RESULTS: The Arg/Arg homozygote
      polymorphism of the XRCC1 gene was associated with an increased risk of stomach
      cancer in the Thai population (OR adj, 3.7; 95%CI, 1.30-10.72) compared with
      Gln/Gln homozygosity. The effect of the XRCC1gene on the risk of stomach cancer
      was modified by both a high intake of vegetable oils and salt (p = 0.036 and p =
      0.014), particularly for the Arg/Arg homozygous genotype. There were, however, no
      additive effects on the risk of stomach cancer between variants of the XRCC1gene
      and smoking,alcohol or pork oil consumption. CONCLUSIONS: The effect of the XRCC1
      gene homozygosity, particularly Arg/Arg, on the risk for stomach cancer was
      elevated by a high intake of vegetable oils and salt.

PMID- 29020931
TI  - Weight management during pregnancy: a qualitative study of women's and care
      providers' experiences and perspectives.
AB  - BACKGROUND: Obesity during pregnancy is a serious health problem for women and
      their children. Despite the high prevalence of high body mass index (BMI) among
      women of reproductive age in high-income countries, there is insufficient
      evidence to inform practice and policy about weight management for women with
      high BMI who are pregnant. The aim of this project was to describe women's and
      midwives' experiences and perspectives of care for weight management during
      pregnancy in Melbourne, Australia. METHODS: A qualitative study. Semi-structured
      interviews were conducted with pregnant women and midwives. Transcripts were
      analysed thematically. RESULTS: A total of 17 women and 2 midwives were
      interviewed. Five themes were identified: 1. Reluctance to and difficulties
      discussing weight and its implications; 2. Barriers to providing appropriate
      pregnancy care for women with high BMI; 3. Inconsistent weighing practices; 4.
      Beliefs about the causes of obesity; and 5. Opportunities to assist women to
      manage their weight. Although most women were satisfied with the pregnancy care
      they had received, both women and midwives expressed concerns about effective
      weight management during pregnancy. These included constraints on discussing
      weight, difficulties accessing appropriate resources and additional support from
      other health care providers, and inconsistent weighing practices. CONCLUSIONS:
      The findings suggest that women with high BMI would benefit from additional
      information and support about weight management prior to conception, during
      pregnancy, and postnatally.

PMID- 29020932
TI  - Difficult conversations: Australian Indigenous patients' views on kidney
      transplantation.
AB  - BACKGROUND: Indigenous Australians suffer a disproportionate burden of end stage
      kidney disease (ESKD) but are significantly less likely to receive a transplant.
      This study explores Indigenous ESKD patients' views on transplantation as a
      treatment option. METHODS: The Improving Access to Kidney Transplants (IMPAKT)
      research program investigated barriers to kidney transplantation for Indigenous
      Australians. An interview study, conducted in 2005-2006, elicited illness
      experience narratives from 146 Indigenous patients, including views on
      transplant. Interviews were conducted at 26 sites that collectively treat the
      majority of Indigenous ESKD patients. Key themes were identified via team
      consensus meetings, providing a flexible framework and focus for continued
      coding. RESULTS: Four inter-related themes were identified in patient commentary:
      a very high level (90% of respondents) of positive interest in transplantation;
      patients experienced a range of communication difficulties and felt uninformed
      about transplant; family involvement in decision-making was constrained by
      inadequate information; and patients needed to negotiate cultural and social
      sensitivities around transplantation. CONCLUSIONS: Indigenous ESKD patients
      demonstrated an intense interest in transplantation preferring deceased over
      living kidney donation. Patients believe transplant is the path most likely to
      support the re-establishment of their 'normal' family life. Patients described
      themselves as poorly informed; most had only a rudimentary knowledge of the
      notion of transplant but no understanding of eligibility criteria, the transplant
      procedure and associated risks. Patients experienced multiple communication
      barriers that - taken together - undermine their engagement in treatment decision
      making. Families and communities are disempowered because they also lack
      information to reach a shared understanding of transplantation. Cultural
      sensitivities associated with transplantation were described but these did not
      appear to constrain patients in making choices about their own health. Transplant
      units and local treatment providers should collaborate to develop user-friendly,
      culturally informed and region-specific patient education programs. Quality
      improvement cycles should underpin the development of national guidelines for
      patient education. Noting Indigenous patients' intense interest in
      transplantation, and nephrologists' concerns regarding poor transplant outcomes,
      research should prioritise exploring the predictors of transplant outcomes for
      Indigenous Australians.

PMID- 29020933
TI  - Partially covered metal stents have longer patency than uncovered and fully
      covered metal stents in the management of distal malignant biliary obstruction: a
      retrospective study.
AB  - BACKGROUND: Self-expandable metal stents (SEMSs) are widely used for malignant
      biliary obstructions. Nitinol-covered SEMSs have been developed to improve stent
      patency. Currently, SEMSs may be uncovered, partially covered, or fully covered;
      however, there is no consensus on the best stent type for the management of
      malignant distal biliary obstruction (MDBO). METHODS: Patients with unresectable
      MDBO receiving SEMS (WallflexTM) were retrospectively analyzed. Time to recurrent
      biliary obstruction (TRBO) and survival time were compared among the three types
      of SEMSs. Univariate and multivariate analyses were performed to identify risk
      factors for stent dysfunction. RESULTS: In total, 101 patients received SEMSs for
      unresectable MDBO (44 uncovered, 28 partially covered, and 29 fully covered
      SEMSs). Median survival time was 200, 168, and 276 days in the uncovered,
      partially covered, and fully covered SEMSs groups, respectively. There were no
      differences in survival among the three groups. Median TRBO was 199, 444, and 194
      days in the uncovered, partially covered, and fully covered SEMSs groups,
      respectively. Partially covered SEMSs had longer TRBO than uncovered (p = 0.013)
      and fully covered (p = 0.010) SEMSs. Tumor ingrowth occurred only with uncovered
      SEMSs and stent migration occurred only with fully covered SEMSs. Multivariate
      analyses confirmed that partially covered SEMSs have lower risk of dysfunction.
      CONCLUSIONS: Partially covered SEMSs with a proximal uncovered flared end have
      longer patency than uncovered and fully covered SEMSs by preventing tumor
      ingrowth and stent migration.

PMID- 29020934
TI  - Transcriptome analyses reveal SR45 to be a neutral splicing regulator and a
      suppressor of innate immunity in Arabidopsis thaliana.
AB  - BACKGROUND: Regulation of pre-mRNA splicing diversifies protein products and
      affects many biological processes. Arabidopsis thaliana Serine/Arginine-rich 45
      (SR45), regulates pre-mRNA splicing by interacting with other regulatory proteins
      and spliceosomal subunits. Although SR45 has orthologs in diverse eukaryotes,
      including human RNPS1, the sr45-1 null mutant is viable. Narrow flower petals and
      reduced seed formation suggest that SR45 regulates genes involved in diverse
      processes, including reproduction. To understand how SR45 is involved in the
      regulation of reproductive processes, we studied mRNA from the wild-type and sr45
      1 inflorescences using RNA-seq, and identified SR45-bound RNAs by
      immunoprecipitation. RESULTS: Using a variety of bioinformatics tools, we
      identified a total of 358 SR45 differentially regulated (SDR) genes, 542 SR45
      dependent alternative splicing (SAS) events, and 1812 SR45-associated RNAs
      (SARs). There is little overlap between SDR genes and SAS genes, and neither set
      of genes is enriched for flower or seed development. However, transcripts from
      reproductive process genes are significantly overrepresented in SARs. In
      exploring the fate of SARs, we found that a total of 81 SARs are subject to
      alternative splicing, while 14 of them are known Nonsense-Mediated Decay (NMD)
      targets. Motifs related to GGNGG are enriched both in SARs and near different
      types of SAS events, suggesting that SR45 recognizes this motif directly. Genes
      involved in plant defense are significantly over-represented among genes whose
      expression is suppressed by SR45, and sr45-1 plants do indeed show enhanced
      immunity. CONCLUSION: We find that SR45 is a suppressor of innate immunity. We
      find that a single motif (GGNGG) is highly enriched in both RNAs bound by SR45
      and in sequences near SR45- dependent alternative splicing events in
      inflorescence tissue. We find that the alternative splicing events regulated by
      SR45 are enriched for this motif whether the effect of SR45 is activation or
      repression of the particular event. Thus, our data suggests that SR45 acts to
      control splice site choice in a way that defies simple categorization as an
      activator or repressor of splicing.

PMID- 29020935
TI  - A retrospective cohort study to predict severe dengue in Honduran patients.
AB  - BACKGROUND: An important challenge in the identification of dengue is how to
      predict which patients will go on to experience severe illness, which is
      typically characterized by fever, thrombocytopenia, haemorrhagic manifestations,
      and plasma leakage. Accurate prediction could result in the appropriate hospital
      triage of high risk patients. The objective of this study was to identify
      clinical factors observed within the first 24 h of hospital admission that could
      predict subsequent severe dengue. METHODS: We conducted a retrospective cohort
      study of 320 patients with febrile illness who had confirmation of dengue within
      one week of admission, using data from the 2009-2010 Honduras Epidemiological
      Survey for Dengue. The outcome measure was plasma leakage defined using
      hemoconcentration >=15% as determined by serial hematocrit testing. We conducted
      univariable analysis and multivariable logistic regression analysis to construct
      a predictive model for severe dengue. RESULTS: Thirty-four (10.6%) of patients in
      the 320 patient cohort had hemoconcentration >=15%. In the final multivariable
      logistic regression model the presence of ascites, OR 7.29, 95% CI 1.85 to 28.7,
      and a platelet count <50,000 platelets/mm3 at admission, OR 3.02, 95% CI 1.42 to
      6.42, were significantly associated with plasma leakage, while the presence of
      petechiae, OR 0.24 95% CI 0.080 to 0.73, and headache, OR 0.38, 95% CI 0.15 to
      0.95, were negatively associated with leakage. Using an estimated probability of
      7% as a threshold for a person being considered a severe case correctly predicted
      26 of the 34 severe cases (sensitivity 76.4%) and 201 of the 286 non-severe cases
      (specificity of 70.3%) for a percentage correctly classified of 70.9%.
      CONCLUSION: We identified signs and symptoms that can correctly identify a
      majority of patients who eventually develop severe dengue in Honduras. It will be
      important to further refine our models and validate them in other populations.

PMID- 29020936
TI  - Staggering the dose of sugammadex lowers risks for severe emergence cough: a
      randomized control trial.
AB  - BACKGROUND: Cough on emergence has been reported as a common adverse reaction
      with sugammadex reversal. We investigated if staggering the dose of sugammadex
      will reduce emergence cough in a single-center, randomized, double-blinded study.
      METHODS: A hundred and twenty ASA 1-3 adults were randomly reversed with 1 mg/kg
      sugammadex prior to extubation followed by another 1 mg/kg immediately after
      extubation (staggered group), single dose of 2 mg/kg sugammadex (single bolus
      group) or neostigmine 0.02 mg/kg with glycopyrrolate (neostigmine group).
      RESULTS: We found 70% of patients (n = 28) reversed with single boluses of
      sugammadex had Grade 3 emergence cough compared to 12.5% (n = 5) in the staggered
      sugammadex group and 17.5% (n = 7) in the neostigmine group (p < 0.001). Besides
      cough, emergence agitation also appeared highest in the single bolus sugammadex
      group (n = 14, 35%, p = 0.005). On the other hand, staggering sugammadex lowered
      risks of developing severe cough (RR 0.2, p < 0.001) and agitation (RR 0.43, p =
      0.010) on emergence in addition to cough (RR 0.25, p = 0.039) and early sore
      throat (RR 0.70, p = 0.036) in the post-anesthetic care unit. The risks for
      severe emergence cough (RR 0.86, p = 0.762), severe cough in the post-anesthetic
      care unit (RR 1.0, p = 1.000) and sore throat (RR 1.17, p = 0.502) were also not
      different between the staggered sugammadex group and control given neostigmine.
      In terms of timing, there was no delay in time taken from discontinuing
      anesthetic agents to reversal and extubation if sugammadex was staggered
      (emergence time 6.0 +/- 3.2 s, p = 0.625 and reversal time 6.5 +/- 3.5, p =
      0.809). CONCLUSIONS: Staggering the dose of sugammadex for reversal will
      effectively decrease common emergence and early postoperative complications.
      TRIAL REGISTRATION: ANZCTR Number ACTRN12616000116426 . Retrospectively
      registered on 2nd February 2016.

PMID- 29020937
TI  - The prognostic value of pretreatment tumor apparent diffusion coefficient values
      in nasopharyngeal carcinoma.
AB  - BACKGROUND: Diffusion-weighted MR imaging (DWI) has increasingly contributed to
      the management of nasopharyngeal carcinoma (NPC) patients. The objective of this
      paper was to explore the prognostic significance of apparent diffusion
      coefficient (ADC) values in 93 NPC patients. METHODS: This retrospective study
      included 93 newly diagnosed NPC patients. Pretreatment ADC values were determined
      and compared with patients' age, gender, alcohol intake, smoking, tumor volume,
      pathological type, tumor stage, and nodal stage. Using the Kaplan-Meier method,
      overall survival (OS), local relapse-free survival (LRFS), and distant metastasis
      free survival (DMFS) were calculated and the values compared between the low and
      high ADC groups. Multivariate analysis of ADC values and other 9 clinical
      parameters was performed using a Cox proportional hazards model to test the
      independent significance for OS, LRFS and DMFS. RESULTS: The mean ADC value for
      the initial nasopharyngeal tumors was 0.72 * 10-3 mm2/s (range: 0.48-0.97 * 10-3
      mm2/s). There was no significant difference between pretreatment ADCs and
      patient' gender, age, smoking, alcohol intake, or tumor stage. A significant
      difference in the ADCs for different N stages (P = 0.022) and correlation with
      initial tumor volume (r = -0.26, P = 0.012) were observed. In comparison, the ADC
      value for undifferentiated carcinoma was lower than that for other 3 pathological
      types. With a median follow-up period of 50 months, the 3-year and 5-year OS
      rates were 88.2% and 83.3%, respectively, 3-year and 5-year LRFS rates were 93.5%
      and 93.3%, respectively, and 3-year and 5-year DMFS rates were 83.9% and 83.3%,
      respectively. Patients with tumor ADC values >=0.72 * 10-3 mm2/s exhibited longer
      OS and LRFS periods compared with tumor ADC values <0.72 * 10-3 mm2/s, with P
      values 0.036 and 0.018, respectively. In addition, patients with deaths or
      recurrences or distant metastasis had significant lower ADC values than those
      without disease failures. According to a multivariate analysis using the Cox
      proportional hazard test, ADC values showed a significant correlation with OS (P
      = 0.0004), LRFS (P = 0.0009), and DMFS (P < 0.0001), respectively. CONCLUSIONS:
      Pretreatment tumor ADC values supposed to be a noninvasive important prognostic
      parameter for NPC.

PMID- 29020938
TI  - Trends in levels of self-reported psychological distress among individuals who
      seek psychiatric services over eight years: a comparison between age groups in
      three population surveys in Stockholm County.
AB  - BACKGROUND: Psychiatric service use has increased in Sweden and in other
      developed countries, particularly among young people. Possible explanations
      include lower threshold for help-seeking among young people, but evidence is
      scarce. METHODS: We analysed the 2002, 2006 and 2010 Stockholm public health
      surveys for changes in the mean level of psychological distress among adult users
      of psychiatric in- and outpatient services in four age groups: 18-24, 25-44, 45
      64 and >=65 years. Psychological distress was measured via the 12-item General
      Health Questionnaire (GHQ-12), using the Likert scoring method 0-1-2-3. In- and
      out-patient psychiatric service use within 6 months from the surveys was obtained
      from registers. RESULTS: The mean level of distress among young adults 18-24
      years who utilize psychiatric services decreased between 2002 (mean GHQ-12 score,
      95% confidence interval 20.5, 18.1-23.0) and 2010 (16.2, 14.6-17.7), while it
      remained fairly stable in older age groups. Results were similar in sex
      stratified analyses, although the decrease was statistically significant only
      among young women 18-24 years. At the end of the follow-up, the level of distress
      among patients was similar for all age-groups. CONCLUSIONS: There were no
      differences between age groups in the level of distress when seeking care at the
      end of the follow-up period, supporting that there is no age-specific over- or
      under-consumption of psychiatric care in later years. However, the lowered
      threshold for help-seeking among young adults over time might have contributed to
      increases in psychiatric service use in the young age group. Public health policy
      and service delivery planning should consider the needs of the widening group of
      young users of psychiatric services.

PMID- 29020939
TI  - A transcriptomic approach to study the effect of long-term starvation and diet
      composition on the expression of mitochondrial oxidative phosphorylation genes in
      gilthead sea bream (Sparus aurata).
AB  - BACKGROUND: The impact of nutritional status and diet composition on
      mitochondrial oxidative phosphorylation (OXPHOS) in fish remains largely unknown.
      To identify biomarkers of interest in nutritional studies, herein we obtained a
      deep-coverage transcriptome by 454 pyrosequencing of liver and skeletal muscle
      cDNA normalised libraries from long-term starved gilthead sea bream (Sparus
      aurata) and fish fed different diets. RESULTS: After clean-up of high-throughput
      deep sequencing reads, 699,991 and 555,031 high-quality reads allowed de novo
      assembly of liver and skeletal muscle sequences, respectively (average length:
      374 and 441 bp; total megabases: 262 and 245 Mbp). An additional incremental
      assembly was completed by integrating data from both tissues (hybrid assembly).
      Assembly of hybrid, liver and skeletal muscle transcriptomes yielded,
      respectively, 19,530, 11,545 and 10,599 isotigs (average length: 1330, 1208 and
      1390 bp, respectively) that were grouped into 15,954, 10,033 and 9189 isogroups.
      Following annotation, hybrid transcriptomic data were used to construct an
      oligonucleotide microarray to analyse nutritional regulation of the expression of
      129 genes involved in OXPHOS in S. aurata. Starvation upregulated cytochrome c
      oxidase components and other key OXPHOS genes in the liver, which exhibited
      higher sensitive to food deprivation than the skeletal muscle. However, diet
      composition affected OXPHOS in the skeletal muscle to a greater extent than in
      the liver: most of genes upregulated under starvation presented higher expression
      among fish fed a high carbohydrate/low protein diet. CONCLUSIONS: Our findings
      indicate that the expression of coenzyme Q-binding protein (COQ10), cytochrome c
      oxidase subunit 6A2 (COX6A2) and ADP/ATP translocase 3 (SLC25A6) in the liver,
      and cytochrome c oxidase subunit 5B isoform 1 (COX5B1) in the liver and the
      skeletal muscle, are sensitive markers of the nutritional condition that may be
      relevant to assess the effect of changes in the feeding regime and diet
      composition on fish farming.

PMID- 29020940
TI  - The epidemiology and transmission of methicillin-resistant Staphylococcus aureus
      in the community in Singapore: study protocol for a longitudinal household study.
AB  - BACKGROUND/AIM: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the
      most common multidrug-resistant organisms in healthcare settings worldwide, but
      little is known about MRSA transmission outside of acute healthcare settings
      especially in Asia. We describe the methods for a prospective longitudinal study
      of MRSA prevalence and transmission. METHODS: MRSA-colonized individuals were
      identified from MRSA admission screening at two tertiary hospitals and recruited
      together with their household contacts. Participants submitted self-collected
      nasal, axilla and groin (NAG) swabs by mail for MRSA culture at baseline and
      monthly thereafter for 6 months. A comparison group of households of MRSA
      negative patients provided swab samples at one time point. In a validation sub
      study, separate swabs from each site were collected from randomly selected
      individuals, to compare MRSA detection rates between swab sites, and between
      samples collected by participants versus those collected by trained research
      staff. Information on each participant's demographic information, medical status
      and medical history, past healthcare facilities usage and contacts, and personal
      interactions with others were collected using a self-administered questionnaire.
      DISCUSSION/CONCLUSION: Understanding the dynamics of MRSA persistence and
      transmission in the community is crucial to devising and evaluating successful
      MRSA control strategies. Close contact with MRSA colonized patients may to be
      important for MRSA persistence in the community; evidence from this study on the
      extent of community MRSA could inform the development of household- or community
      based interventions to reduce MRSA colonization of close contacts and subsequent
      re-introduction of MRSA into healthcare settings. Analysis of longitudinal data
      using whole-genome sequencing will yield further information regarding MRSA
      transmission within households, with significant implications for MRSA infection
      control outside acute hospital settings.

PMID- 29020941
TI  - Fine mapping of a QTL affecting levels of skatole on pig chromosome 7.
AB  - BACKGROUND: Previous studies in the Norwegian pig breeds Landrace and Duroc have
      revealed a QTL for levels of skatole located in the region 74.7-80.5 Mb on SSC7.
      Skatole is one of the main components causing boar taint, which gives an
      undesirable smell and taste to the pig meat when heated. Surgical castration of
      boars is a common practice to reduce the risk of boar taint, however, a selection
      for boars genetically predisposed for low levels of taint would help eliminating
      the need for castration and be advantageous for both economic and welfare
      reasons. In order to identify the causal mutation(s) for the QTL and/or identify
      genetic markers for selection purposes we performed a fine mapping of the SSC7
      skatole QTL region. RESULTS: A dense set of markers on SSC7 was obtained by whole
      genome re-sequencing of 24 Norwegian Landrace and 23 Duroc boars. Subsets of 126
      and 157 SNPs were used for association analyses in Landrace and Duroc,
      respectively. Significant single markers associated with skatole spanned a large
      4.4 Mb region from 75.9-80.3 Mb in Landrace, with the highest test scores found
      in a region between the genes NOVA1 and TGM1 (p < 0.001). The same QTL was
      obtained in Duroc and, although less significant, with associated SNPs spanning a
      1.2 Mb region from 78.9-80.1 Mb (p < 0.01). The highest test scores in Duroc were
      found in genes of the granzyme family (GZMB and GZMH-like) and STXBP6. Haplotypes
      associated with levels of skatole were identified in Landrace but not in Duroc,
      and a haplotype block was found to explain 2.3% of the phenotypic variation for
      skatole. The SNPs in this region were not associated with levels of sex steroids.
      CONCLUSIONS: Fine mapping of a QTL for skatole on SSC7 confirmed associations of
      this region with skatole levels in pigs. The QTL region was narrowed down to 4.4
      Mb in Landrace and haplotypes explaining 2.3% of the phenotypic variance for
      skatole levels were identified. Results confirmed that sex steroids are not
      affected by this QTL region, making these markers attractive for selection
      against boar taint.

PMID- 29020942
TI  - Peripherally inserted central catheter-related bloodstream infection due to
      Tsukamurella pulmonis: a case report and literature review.
AB  - BACKGROUND: Tsukamurella pulmonis is an aerobic gram-positive and rod-shaped
      organism that causes central catheter-related bloodstream infections in
      immunocompromised hosts. However, peripherally inserted central catheter (PICC)
      related bloodstream infections due to this organism have not been reported. CASE
      PRESENTATION: We describe a case of a 48-year-old man with acquired
      immunodeficiency syndrome and diffuse large B cell lymphoma who received five
      courses of chemotherapy including rituximab , cyclophosphamide , doxorubicin
      hydrochloride , vincristine , and prednisone via a PICC. Five days after the last
      chemotherapy course, he presented with a high fever and shaking chills. His
      absolute neutrophil count was 4200/MUL. Cultures obtained from blood and PICC
      culture revealed T. pulmonis. The colony count of T. pulmonis grown from PICC
      culture was 103 colony-forming units. Therefore, he was diagnosed with T.
      pulmonis bacteremia resulting from PICC-related bloodstream infection. The
      patient's condition improved and he became afebrile within 48 h after intravenous
      administration of cefozopran hydrochloride, which is a fourth generation
      cephalosporin. CONCLUSIONS: PICCs can be associated with T. pulmonis bacteremia,
      and fourth generation cephalosporins may be effective treatment.

PMID- 29020943
TI  - Rational use of Xpert testing in patients with presumptive TB: clinicians should
      be encouraged to use the test-treat threshold.
AB  - BACKGROUND: A recently published Ugandan study on tuberculosis (TB) diagnosis in
      HIV-positive patients with presumptive smear-negative TB, which showed that out
      of 90 patients who started TB treatment, 20% (18/90) had a positive Xpert MTB/RIF
      (Xpert) test, 24% (22/90) had a negative Xpert test, and 56% (50/90) were started
      without Xpert testing. Although Xpert testing was available, clinicians did not
      use it systematically. Here we aim to show more objectively the process of
      clinical decision-making. First, we estimated that pre-test probability of TB, or
      the prevalence of TB in smear-negative HIV infected patients with signs of
      presumptive TB in Uganda, was 17%. Second, we argue that the treatment threshold,
      the probability of disease at which the utility of treating and not treating is
      the same, and above which treatment should be started, should be determined. In
      Uganda, the treatment threshold was not yet formally established. In Rwanda, the
      calculated treatment threshold was 12%. Hence, one could argue that the threshold
      was reached without even considering additional tests. Still, Xpert testing can
      be useful when the probability of disease is above the treatment threshold, but
      only when a negative Xpert result can lower the probability of disease enough to
      cross the treatment threshold. This occurs when the pre-test probability is lower
      than the test-treat threshold, the probability of disease at which the utility of
      testing and the utility of treating without testing is the same. We estimated
      that the test-treatment threshold was 28%. Finally, to show the effect of the
      presence or absence of arguments on the probability of TB, we use confirming and
      excluding power, and a log10 odds scale to combine arguments. CONCLUSION: If the
      pre-test probability is above the test-treat threshold, empirical treatment is
      justified, because even a negative Xpert will not lower the post-test probability
      below the treatment threshold. However, Xpert testing for the diagnosis of TB
      should be performed in patients for whom the probability of TB was lower than the
      test-treat threshold. Especially in resource constrained settings clinicians
      should be encouraged to take clinical decisions and use scarce resources
      rationally.

PMID- 29020944
TI  - A convenient UHPLC-MS/MS method for routine monitoring of plasma and brain levels
      of nicotine and cotinine as a tool to validate newly developed preclinical
      smoking model in mouse.
AB  - BACKGROUND: A sensitive, rapid and selective UHPLC-MS/MS method has been
      developed and validated for the quantification of Nicotine (NT) and Cotinine (CN)
      using Continine-d 3 as internal standard (IS) as per FDA guidelines. Sample
      preparation involved simple protein precipitation of 20 uL mouse plasma or brain
      homogenate using acetonitrile at 1:8 ratio. Mass Spectrometer was operated in
      positive polarity under the multiple reaction-monitoring mode using electro spray
      ionization technique and the transitions of m/z 163.2 -> 132.1, 177.2 -> 98.0 and
      180.2 -> 101.2 were used to measure the NT, CN and IS, respectively. The elution
      of NT, CN and IS are at 1.89, 1.77 and 1.76 min, respectively. This was achieved
      with a gradient mobile phase consisting of 5 mM ammonium bicarbonate,
      acetonitrile and methanol (3:1, v/v) at a flow rate of 0.3 mL/min on a Kinetex
      EVO C18 column. The method was validated with a lower limit of quantitation 3.0
      ng/mL in mouse plasma and brain for both the analytes. RESULTS: A linear response
      function was established for the range of concentrations 3-200 (r > 0.995) for NT
      and 3-600 ng/mL (r > 0.995) for CN. The intra- and inter-day precision values met
      the acceptance criteria. NT and CN are stable in the battery of stability studies
      viz., stock solution, bench-top and auto-sampler. CONCLUSION: This method was
      successfully utilized to validate a newly developed preclinical smoking model in
      mice.

PMID- 29020946
TI  - The transcriptome of the developing grain: a resource for understanding seed
      development and the molecular control of the functional and nutritional
      properties of wheat.
AB  - BACKGROUND: Wheat is one of the three major cereals that have been domesticated
      to feed human populations. The composition of the wheat grain determines the
      functional properties of wheat including milling efficiency, bread making, and
      nutritional value. Transcriptome analysis of the developing wheat grain provides
      key insights into the molecular basis for grain development and quality. RESULTS:
      The transcriptome of 35 genotypes was analysed by RNA-Seq at two development
      stages (14 and 30 days-post-anthesis, dpa) corresponding to the mid stage of
      development (stage Z75) and the almost mature seed (stage Z85). At 14dpa, most of
      the transcripts were associated with the synthesis of the major seed components
      including storage proteins and starch. At 30dpa, a diverse range of genes were
      expressed at low levels with a predominance of genes associated with seed defence
      and stress tolerance. RNA-Seq analysis of changes in expression between 14dpa and
      30dpa stages revealed 26,477 transcripts that were significantly differentially
      expressed at a FDR corrected p-value cut-off at <=0.01. Functional annotation and
      gene ontology mapping was performed and KEGG pathway mapping allowed grouping
      based upon biochemical linkages. This analysis demonstrated that photosynthesis
      associated with the pericarp was very active at 14dpa but had ceased by 30dpa.
      Recently reported genes for flour yield in milling and bread quality were found
      to influence wheat quality largely due to expression patterns at the earlier seed
      development stage. CONCLUSIONS: This study serves as a resource providing an
      overview of gene expression during wheat grain development at the early (14dpa)
      and late (30dpa) grain filling stages for use in studies of grain quality and
      nutritional value and in understanding seed biology.

PMID- 29020945
TI  - Dehydration induced transcriptomic responses in two Tibetan hulless barley
      (Hordeum vulgare var. nudum) accessions distinguished by drought tolerance.
AB  - BACKGROUND: The harsh environment on the Qinghai-Tibetan Plateau gives Tibetan
      hulless barley (Hordeum vulgare var. nudum) great ability to resist adversities
      such as drought, salinity, and low temperature, and makes it a good subject for
      the analysis of drought tolerance mechanism. To elucidate the specific gene
      networks and pathways that contribute to its drought tolerance, and for
      identifying new candidate genes for breeding purposes, we performed a
      transcriptomic analysis using two accessions of Tibetan hulless barley, namely
      Z772 (drought-tolerant) and Z013 (drought-sensitive). RESULTS: There were more up
      regulated genes of Z772 than Z013 under both mild (5439-VS-2604) and severe (7203
      VS-3359) dehydration treatments. Under mild dehydration stress, the pathways
      exclusively enriched in drought-tolerance genotype Z772 included Protein
      processing in endoplasmic reticulum, tricarboxylic acid (TCA) cycle, Wax
      biosynthesis, and Spliceosome. Under severe dehydration stress, the pathways that
      were mainly enriched in Z772 included Carbon fixation in photosynthetic
      organisms, Pyruvate metabolism, Porphyrin and chlorophyll metabolism. The main
      differentially expressed genes (DEGs) in response to dehydration stress and genes
      whose expression was different between tolerant and sensitive genotypes were
      presented in this study, respectively. The candidate genes for drought tolerance
      were selected based on their expression patterns. CONCLUSIONS: The RNA-Seq data
      obtained in this study provided an initial overview on global gene expression
      patterns and networks that related to dehydration shock in Tibetan hulless
      barley. Furthermore, these data provided pathways and a targeted set of candidate
      genes that might be essential for deep analyzing the molecular mechanisms of
      plant tolerance to drought stress.

PMID- 29020947
TI  - Early adversity and psychiatric symptoms - a prospective study on Ethiopian
      mothers and their children.
AB  - BACKGROUND: Maternal exposure to adversity during the perinatal period has been
      associated with increased susceptibility for psychiatric symptoms in the
      offspring. The aim of this study was to investigate a possible developmental
      effect of maternal perinatal stressors on emotional and behavioural symptoms in
      the offspring in a developing country. METHODS: We followed an Ethiopian birth
      cohort (N = 358), assessing intimate partner violence (IPV) and maternal
      psychiatric symptoms during the perinatal period and at follow-up 10 years later,
      as a proxy for adversity, and maternal ratings on the Child Behavior Checklist
      (CBCL) 10 years later as the outcome. RESULTS: Among the women, exposure to IPV
      was common (60.6%) during the perinatal period and predicted IPV (29.9% of the
      mothers) at follow-up (rho = 0.132; p = 0.012). There was also an association
      between maternal psychiatric symptoms at the two time points (rho = 0.136; p =
      0.010) and between maternal symptoms and IPV. Current maternal symptoms of
      anxiety and depression (beta = 0.057; p < 0.001), but not during the perinatal
      period, were associated with child CBCL-scores. CONCLUSION: Our findings do not
      support the hypothesis that early adversity increase susceptibility for
      psychiatric symptoms. However, the findings emphasize the public health problem
      of IPV in this population, adding to the women's mental health problem.

PMID- 29020948
TI  - Informed walks: whispering hints to gene hunters inside networks' jungle.
AB  - BACKGROUND: Systemic approaches offer a different point of view on the analysis
      of several types of molecular associations as well as on the identification of
      specific gene communities in several cancer types. However, due to lack of
      sufficient data needed to construct networks based on experimental evidence,
      statistical gene co-expression networks are widely used instead. Many efforts
      have been made to exploit the information hidden in these networks. However,
      these approaches still need to capitalize comprehensively the prior knowledge
      encrypted into molecular pathway associations and improve their efficiency
      regarding the discovery of both exclusive subnetworks as candidate biomarkers and
      conserved subnetworks that may uncover common origins of several cancer types.
      METHODS: In this study we present the development of the Informed Walks model
      based on random walks that incorporate information from molecular pathways to
      mine candidate genes and gene-gene links. The proposed model has been applied to
      TCGA (The Cancer Genome Atlas) datasets from seven different cancer types,
      exploring the reconstructed co-expression networks of the whole set of genes and
      driving to highlighted sub-networks for each cancer type. In the sequel, we
      elucidated the impact of each subnetwork on the indication of underlying
      exclusive and common molecular mechanisms as well as on the short-listing of
      drugs that have the potential to suppress the corresponding cancer type through a
      drug-repurposing pipeline. CONCLUSIONS: We have developed a method of gene
      subnetwork highlighting based on prior knowledge, capable to give fruitful
      insights regarding the underlying molecular mechanisms and valuable input to drug
      repurposing pipelines for a variety of cancer types.

PMID- 29020950
TI  - Differential gene expression in disease: a comparison between high-throughput
      studies and the literature.
AB  - BACKGROUND: Differential gene expression is important to understand the
      biological differences between healthy and diseased states. Two common sources of
      differential gene expression data are microarray studies and the biomedical
      literature. METHODS: With the aid of text mining and gene expression analysis we
      have examined the comparative properties of these two sources of differential
      gene expression data. RESULTS: The literature shows a preference for reporting
      genes associated to higher fold changes in microarray data, rather than genes
      that are simply significantly differentially expressed. Thus, the resemblance
      between the literature and microarray data increases when the fold-change
      threshold for microarray data is increased. Moreover, the literature has a
      reporting preference for differentially expressed genes that (1) are
      overexpressed rather than underexpressed; (2) are overexpressed in multiple
      diseases; and (3) are popular in the biomedical literature at large.
      Additionally, the degree to which diseases are similar depends on whether
      microarray data or the literature is used to compare them. Finally, vaguely
      qualified reports of differential expression magnitudes in the literature have
      only small correlation with microarray fold-change data. CONCLUSIONS: Reporting
      biases of differential gene expression in the literature can be affecting our
      appreciation of disease biology and of the degree of similarity that actually
      exists between different diseases.

PMID- 29020949
TI  - Modelling dynamic change of malaria transmission in holoendemic setting (Dielmo,
      Senegal) using longitudinal measures of antibody prevalence to Plasmodium
      falciparum crude schizonts extract.
AB  - BACKGROUND: Evaluation of local Plasmodium falciparum malaria transmission has
      been investigated previously using the reversible catalytic model based on
      prevalence of antibody responses to single antigen to estimate seroconversion
      rates. High correlations were observed between seroconversion rates and
      entomological inoculation rates (EIR). However, in this model, the effects of
      malaria control interventions and clinical episodes on serological measurements
      were not assessed. This study monitors the use of antibody responses to P.
      falciparum crude extracts for assessing malaria transmission, compares
      seroconversion rates estimated from longitudinal data to those derived from cross
      sectional surveys and investigates the effects of malaria control interventions
      on these measures in an area of declining malaria transmission. In addition, the
      validity of this model was evaluated by comparison with the alternative model.
      METHODS: Five cross-sectional surveys were carried out at the end of the wet
      season in Dielmo, a malaria-endemic Senegalese rural area in 2000, 2002, 2008,
      2010 and 2012. Antibodies against schizonts crude extract of a local P.
      falciparum strain adapted to culture (Pf 07/03) were measured by ELISA. Age
      specific seroprevalence model was used both for cross-sectional surveys and
      longitudinal data (combined data of all surveys). RESULTS: A total of 1504 plasma
      samples obtained through several years follow-up of 350 subjects was used in this
      study. Seroconversion rates based on P. falciparum schizonts crude extract were
      estimated for each cross-sectional survey and were found strongly correlated with
      EIR. High variability between SCRs from cross-sectional and longitudinal surveys
      was observed. In longitudinal studies, the alternative catalytic reversible model
      adjusted better with serological data than the catalytic model. Clinical malaria
      attacks and malaria control interventions were found to have significant effect
      on seroconversion. DISCUSSION: The results of the study suggested that crude
      extract was a good serological tool that could be used to assess the level of
      malaria exposure in areas where malaria transmission is declining. However,
      additional parameters such as clinical malaria and malaria control interventions
      must be taken into account for determining serological measurements for more
      accuracy in transmission assessment.

PMID- 29020951
TI  - Paramedic literature search filters: optimised for clinicians and academics.
AB  - BACKGROUND: Search filters aid clinicians and academics to accurately locate
      literature. Despite this, there is no search filter or Medical Subject Headings
      (MeSH) term pertaining to paramedics. Therefore, the aim of this study was to
      create two filters to meet to different needs of paramedic clinicians and
      academics. METHODS: We created a gold standard from a reference set, which we
      measured against single terms and search filters. The words and phrases used
      stemmed from selective exclusion of terms from the previously published
      Prehospital Search Filter 2.0 as well as a Delphi session with an expert panel of
      paramedic researchers. Independent authors deemed articles paramedic-relevant or
      not following an agreed definition. We measured sensitivity, specificity,
      accuracy and number needed to read (NNR). RESULTS: We located 2102 articles of
      which 431 (20.5%) related to paramedics. The performance of single terms was on
      average of high specificity (97.1% (Standard Deviation 7.4%), but of poor
      sensitivity (12.0%, SD 18.7%). The NNR ranged from 1 to 8.6. The sensitivity
      maximising search filter yielded 98.4% sensitivity, with a specificity of 74.3%
      and a NNR of 2. The specificity-maximising filter achieved 88.3% in specificity,
      which only lowered the sensitivity to 94.7%, and thus a NNR of 1.48. CONCLUSIONS:
      We have created the first two paramedic specific search filters, one optimised
      for sensitivity and one optimised for specificity. The sensitivity-maximising
      search filter yielded 98.4% sensitivity, and a NNR of 2. The specificity
      maximising filter achieved 88.3% in specificity, which only lowered the
      sensitivity to 94.7%, and a NNR of 1.48. A paramedic MeSH term is needed.

PMID- 29020952
TI  - Toxoplasma gondii and Neospora caninum in farm-reared ostriches (Struthio
      camelus) in China.
AB  - BACKGROUND: The parasites Toxoplasma gondii (T. gondii) and Neospora caninum (N.
      caninum) are globally distributed; they infect warm-blooded animals, including
      many avian species. The aim of this study was to evaluate the presence of these
      parasites in ostriches from central China. In total, 402 ostrich (Struthio
      camelus) samples (293 hearts, 77 brains, and 32 serum) from slaughterhouses of
      the Henan Province and Hebei Province were collected. The heart juice (n = 283)
      and serum samples (n = 32) were tested for antibodies to T. gondii using the
      modified agglutination test (MAT). Hematoxylin and eosin (H&E) staining,
      immunohistochemical (IHC) staining, and the polymerase chain reaction were used
      to examine the cysts and DNA of T. gondii and N. caninum parasites, respectively.
      RESULTS: Antibodies to T. gondii were detected in 6.4% (20/315) (cut-off, 25). No
      cysts or DNA of T. gondii or N. caninum were observed in any of the 293 hearts
      and 77 brains. CONCLUSION: The results showed a low prevalence of T. gondii
      antibody in ostriches, compared to that in the other animals. N. caninum occurs
      at low to negligible frequencies in ostriches from China. This is the first
      report on screening ostriches in China for T. gondii antibodies.

PMID- 29020953
TI  - "Layers of translation" - evidence literacy in public health practice: a
      qualitative secondary analysis.
AB  - BACKGROUND: Strengthening public health systems has been a concern in Canada in
      the wake of public health emergencies. In one Canadian province, British
      Columbia, a high priority has been placed on the role of evidence to guide
      decision making; however, there are numerous challenges to using evidence in
      practice. The National Collaborating Centre for Methods and Tools therefore
      developed the Evidence Informed Public Health Framework (EIPH), a seven step
      guide to assist public health practitioners to use evidence in practice. We used
      this framework to examine the evidence literacy of public health practitioners in
      BC. METHODS: We conducted a secondary analysis of two separate qualitative
      studies on the public health renewal process in which the use and understanding
      of evidence were key interview questions. Using constant comparative analysis, we
      analyzed the evidence-related data, mapping it to the categories of the EIPH
      framework. RESULTS: Participants require both data and evidence for multiple
      purposes in their daily work; data may be more important to them than research
      evidence. They are keen to provide evidence-based programs in which research
      evidence is balanced with community knowledge and local data. Practitioners
      recognise appraisal as an important step in using evidence, but the type of
      evidence most often used in daily practice does not easily lend itself to
      established methods for appraising research evidence. In the synthesis stage of
      the EIPH process, synthesized evidence in the form of systematic reviews and
      practice guidelines is emphasized. Participants, however, need to synthesize
      across the multiple forms of evidence they use and see the need for more skill
      and resources to help them develop skill in this type of synthesis. CONCLUSIONS:
      Public health practitioners demonstrated a good level of evidence literacy,
      particularly at the collective level in the organization. The EIPH framework
      provides helpful guidance in how to use research evidence in practice, but it
      lacks support on appraising and synthesizing across the various types of evidence
      that practitioners consider essential in their practice. We can better support
      practitioners by appreciating the range of evidence they use and value and by
      creating tools that help them to do this.

PMID- 29020954
TI  - Correction to: Socioeconomic and demographic characterization of an endemic
      malaria region in Brazil by multiple correspondence analysis.
AB  - After publication of the article [1], it has been brought to our attention that
      the y-axis of Fig. 6 has been labeled incorrectly. It should read "linear
      predictor". This has now been corrected in the original article.

PMID- 29020955
TI  - Concomitant aorto-right subclavian artery bypass with off-pump coronary artery
      bypass grafting: a case report.
AB  - BACKGROUND: Atherosclerotic stenosis of the brachiocephalic artery sometimes
      occurs in patients with coronary artery disease, and can cause stroke during the
      perioperative period of coronary artery bypass grafting. CASE PRESENTATION: We
      describe the case of a 77-year old male with severe stenosis of the
      brachiocephalic artery and severe coronary artery disease. He successfully
      underwent aorto-right subclavian artery bypass that was performed concomitantly
      with off-pump coronary artery bypass. CONCLUSION: Concomitant aorto-subclavian
      artery bypass with off-pump coronary artery bypass grafting is a therapeutic
      option that minimizes the risk of perioperative stroke in patients with
      brachiocephalic artery stenosis and coronary artery disease.

PMID- 29020956
TI  - Guaiphenesin-ketamine-xylazine infusion to maintain anesthesia in mules
      undergoing field castration.
AB  - BACKGROUND: In order to determine whether a combination of guaiphenesin, ketamine
      and xylazine can induce safe and satisfactory anaesthesia in mules undergoing
      field castration, eight healthy adult intact male mules were employed. They were
      premedicated with intravenous (IV) xylazine (1.3 mg/kg); an additional dose of
      xylazine (0.3 mg/kg IV) was administered in case of inadequate depth of sedation.
      Anaesthesia was induced with IV thiopental (6 mg/kg). The quality of sedation and
      induction was recorded. Anaesthesia was maintained with an infusion of
      guaiphenesin (50 mg/mL), ketamine (2 mg/mL) and xylazine (1 mg/mL) (GKX). The
      spermatic cord of each testis was infiltrated with 5 mL of 2% lidocaine. During
      anaesthesia heart rate (HR), respiratory rate (RR), rectal temperature (RT) and
      haemoglobin oxygen saturation (SpO2) were measured every 5 min. The data were
      analysed with simple one-way analysis of variance (ANOVA). A P value < 0.05 was
      considered statistically significant. Time of anesthesia, time of surgery and
      time of recovery were recorded. RESULTS: Only one mule required an additional
      dose of xylazine to achieve a satisfactory depth of sedation. Thiopental at the
      dose of 6 mg/kg IV resulted in smooth induction and lateral recumbency in all
      animals. GKX provided adequate anaesthesia to perform castration in all mules.
      Muscle relaxation was deemed adequate and physiological variables remained stable
      and within references values during the anaesthesia and did not change in
      response to surgical stimulation. Time (mean +/- standard deviation) from the end
      of the infusion to sternal recumbency and time from sternal recumbency to
      standing were 27.7 +/- 4.6 and 30.1 +/- 7.7 min, respectively. CONCLUSIONS: The
      combination of xylazine, thiopental and GKX provides satisfactory short-term
      anaesthesia in mules undergoing field castration.

PMID- 29020957
TI  - Social disparities in the prevalence of diabetes in Australia and in the
      development of end stage renal disease due to diabetes for Aboriginal and Torres
      Strait Islanders in Australia and Maori and Pacific Islanders in New Zealand.
AB  - BACKGROUND: Disparities in health status occur between people with differing
      socioeconomic status and disadvantaged groups usually have the highest risk
      exposure and the worst health outcome. We sought to examine the social
      disparities in the population prevalence of diabetes and in the development of
      treated end stage renal disease due to type 1 diabetes which has not previously
      been studied in Australia and New Zealand in isolation from type 2 diabetes.
      METHODS: This observational study examined the population prevalence of diabetes
      in a sample of the Australian population (7,434,492) using data from the National
      Diabetes Services Scheme and of treated end stage renal disease due to diabetes
      using data from the Australian and New Zealand Dialysis and Transplant Registry.
      The data were then correlated with the Australian Bureau of Statistics
      Socioeconomic Indexes for Areas for an examination of socioeconomic disparities.
      RESULTS: There is a social gradient in the prevalence of diabetes in Australia
      with disease incidence decreasing incrementally with increasing affluence
      (Spearman's rho = .765 p < 0.001). There is a higher risk of developing end stage
      renal disease due to type 1 diabetes for males with low socioeconomic status (RR
      1.20; CI 1.002-1.459) in comparison to females with low socioeconomic status. In
      Australia and New Zealand Aboriginal and Torres Strait Islanders, Maori and
      Pacific Islanders appear to have a low risk of end stage renal disease due to
      type 1 diabetes but continue to carry a vastly disproportionate burden of end
      stage renal disease due to type 2 diabetes (RR 6.57 CI 6.04-7.14 & 6.48 CI 6.02
      6.97 respectively p < 0.001) in comparison to other Australian and New
      Zealanders. CONCLUSION: Whilst low socioeconomic status is associated with a
      higher prevalence of diabetes the inverse social gradient seen in this study has
      not previously been reported. The social disparity seen in relation to treated
      end stage renal disease due to type 2 diabetes for Aboriginal and Torres Strait
      Islanders, Maori and Pacific Islanders has changed very little in the past 20
      years. Addressing the increasing incidence of diabetes in Australia requires
      consideration of the underlying social determinants of health.

PMID- 29020958
TI  - Does replacing sedentary behaviour with light or moderate to vigorous physical
      activity modulate inflammatory status in adults?
AB  - BACKGROUND: Sedentary behaviour, obesity and insulin resistance are associated
      with pro-inflammatory status. Limited data on whether physical activity modulates
      inflammatory status and counteracts obesity and insulin resistance associated low
      grade inflammation exist. Our objective was to investigate associations between
      objectively measured physical activity and inflammatory status, and specifically
      whether substituting daily sedentary behaviour with light activity or moderate to
      vigorous physical activity (MVPA), is associated with beneficial alterations to
      the inflammatory profile among middle-aged adults and those at increased
      cardiometabolic risk (obese and insulin resistant subjects). METHODS: Data are
      from a sub-sample of the Mitchelstown cohort; a population-based cross-sectional
      sample of 2047 Irish adults. Physical activity intensity and duration were
      measured in 396 participants for 7-consecutive days using the GENEActiv
      accelerometer. Isotemporal regression analysis examined the associations between
      replacing 30 min per day of sedentary behaviour with equal amounts of light
      activity and MVPA on inflammatory factors (serum acute-phase reactants,
      adipocytokines, pro-inflammatory cytokines and white blood cells (WBC)). RESULTS:
      Reallocating 30 min of sedentary time with MVPA was associated with a more
      favourable inflammatory profile characterized by higher adiponectin and lower
      complement component C3 (C3), leptin, interleukin 6 (IL-6) and WBC concentrations
      (P < 0.05). No significant effects were noted with substitution of sedentary time
      with light activity. Among the obese subjects replacing sedentary behaviour with
      an equivalent amount of MVPA was associated with lower WBC counts (P < 0.05); no
      associations were detected among the insulin resistant (HOMA-IR >75th percentile)
      subjects. Among the non-obese and non-insulin resistant subjects substituting 30
      min of sedentary behaviour with MVPA was associated with decreased C3, IL-6 and
      WBC concentrations. CONCLUSIONS: Replacing sedentary behaviour with MVPA
      modulates pro-inflammatory status. These findings, which highlight the need for
      the developing randomized trials aimed at lowering cardiometabolic risk, warrant
      further investigation.

PMID- 29020959
TI  - Configurable, wearable sensing and vibrotactile feedback system for real-time
      postural balance and gait training: proof-of-concept.
AB  - BACKGROUND: Postural balance and gait training is important for treating persons
      with functional impairments, however current systems are generally not portable
      and are unable to train different types of movements. METHODS: This paper
      describes a proof-of-concept design of a configurable, wearable sensing and
      feedback system for real-time postural balance and gait training targeted for
      home-based treatments and other portable usage. Sensing and vibrotactile feedback
      are performed via eight distributed, wireless nodes or "Dots" (size: 22.5 * 20.5
      * 15.0 mm, weight: 12.0 g) that can each be configured for sensing and/or
      feedback according to movement training requirements. In the first experiment,
      four healthy older adults were trained to reduce medial-lateral (M/L) trunk tilt
      while performing balance exercises. When trunk tilt deviated too far from
      vertical (estimated via a sensing Dot on the lower spine), vibrotactile feedback
      (via feedback Dots placed on the left and right sides of the lower torso) cued
      participants to move away from the vibration and back toward the vertical no
      feedback zone to correct their posture. A second experiment was conducted with
      the same wearable system to train six healthy older adults to alter their foot
      progression angle in real-time by internally or externally rotating their feet
      while walking. Foot progression angle was estimated via a sensing Dot adhered to
      the dorsal side of the foot, and vibrotactile feedback was provided via feedback
      Dots placed on the medial and lateral sides of the mid-shank cued participants to
      internally or externally rotate their foot away from vibration. RESULTS: In the
      first experiment, the wearable system enabled participants to significantly
      reduce trunk tilt and increase the amount of time inside the no feedback zone. In
      the second experiment, all participants were able to adopt new gait patterns of
      internal and external foot rotation within two minutes of real-time training with
      the wearable system. CONCLUSION: These results suggest that the configurable,
      wearable sensing and feedback system is portable and effective for different
      types of real-time human movement training and thus may be suitable for home
      based or clinic-based rehabilitation applications.

PMID- 29020960
TI  - Perspectives in immunotherapy: meeting report from the "Immunotherapy Bridge",
      Napoli, November 30th 2016.
AB  - The complex interactions between the immune system and tumors lead the
      identification of key molecules that govern these interactions:
      immunotherapeutics were designed to overcome the mechanisms broken by tumors to
      evade immune destruction. After the substantial advances in melanoma,
      immunotherapy currently includes many other type of cancers, but the melanoma
      lesson is essential to progress in other type of cancers, since immunotherapy is
      potentially improving clinical outcome in various solid and haematologic
      malignancies. Monotherapy in pre-treated NSCLC is studied and the use of
      nivolumab, pembrolizumab and atezolizumab as second-line of advanced NSCLC is
      demonstrated as well as first line monotherapy and combination therapy in
      metastatic NSCLC studied. Patients with HNSCC have immunotherapeutic promises as
      well: the FDA recently approved moAbs targeting immune checkpoint receptors.
      Nivolumab in combination with ipilumumab showed acceptable safety and encouraging
      antitumor activity in metastatic renal carcinoma. HCCs have significant amounts
      of genomic heterogeneity and multiple oncogenic pathways can be activated: the
      best therapeutic targets identification is ongoing. The treatment of
      advanced/relapsed EOC remain clearly an unmet need: a better understanding of the
      relevant immuno-oncologic pathways and their corresponding biomarkers are
      required. UC is an immunotherapy-responsive disease: after atezolizumab, three
      other PD-L1/PD-L1 inhibitors (nivolumab, durvalumab, and avelumab) were approved
      for treatment of platinum-refractory metastatic urothelial carcinoma. Anti-PD
      1/PD-L1 monotherapy is associated with a modest response rate in metastatic
      breast cancer; the addition of chemotherapy is associated with higher response
      rates. Immunotherapy safety profile is advantageous, although, in contrast to
      conventional chemotherapy: boosting the immune system leads to a unique
      constellation of inflammatory toxicities known as immune-related Adverse Events
      (irAEs) that may warrant the discontinuation of therapy and/or the administration
      of immunosuppressive agents. Research should explore better combination with less
      side effects, the right duration of treatments, combination or sequencing
      treatments with target therapies. At present, treatment decision is based on
      patient's characteristics.

PMID- 29020962
TI  - Manipulation under anesthesia versus physiotherapy treatment in stage two of a
      frozen shoulder: a study protocol for a randomized controlled trial.
AB  - BACKGROUND: There is no consensus about the optimal treatment strategy for frozen
      shoulders (FS). Conservative treatment consisting of intra-articular
      corticosteroid infiltrations and physiotherapy are considered appropriate for
      most patients. However, with a conservative strategy, patients experience a
      prolonged rehabilitation period with a considerable amount of pain and
      disabilities in daily life. Also, at long term, a residual amount of pain and
      restriction of range of motion is frequently reported. Manipulation under
      anesthesia is a short and relative simple procedure with the potential to rapidly
      reduce symptoms and restore the range of motion. The objective of this trial is
      to evaluate the effectiveness of MUA followed by a PT program compared to a PT
      program alone, in the treatment of patients with a stage two FS. We hypothesize
      that the course of the disease can be shortened with MUA with a quicker
      functional recovery. METHODS: This is a prospective, single center, randomized
      controlled trial. Eligible patients will be allocated to either the manipulation
      (MUA) group or the physiotherapy alone (PT) group. In the MUA group manipulation
      will be performed under interscalene block, directly followed by an intensive
      physiotherapy treatment protocol, with the goal to maintain the obtained range of
      motion. Patients allocated to the PT group are given advice and education and
      receive a written protocol to hand out to their physical therapist based on the
      recent guideline of the Dutch Shoulder Network for the treatment of frozen
      shoulders. Descriptive statistics will be used to describe the sample size,
      patients demographics, presence of diabetes mellitus, range of motion, duration
      of symptoms till randomization and will be presented for each treatment group.
      The SPADI is used as primary functional outcome parameter. Secondary outcome
      parameters are; OSS, NPRS, EQ-5D 3-L, passive range of motion, WORQ-UP, duration
      of symptoms, usage of analgesics and adverse events. A sample size of 41 subjects
      in each group was calculated. Follow up is planned after 1,3 and 12 months. The
      length of physiotherapy treatment in both groups is variable, depending on
      individual progression. Differences between groups in outcome parameters will be
      analysed using the linear mixed modelling and the restricted maximum likelihood
      ratio technique for estimating the model parameters. DISCUSSION: Successful
      completion of this trial will provide evidence on the best treatment strategy for
      patients with a stage two frozen shoulder. The results of this study can lead to
      a better understanding for the role of manipulation in the treatment of frozen
      shoulders. TRIAL REGISTRATION: This trial is registered in the Dutch Trial
      Register under the number NTR6182 on the 20th of February 2017.

PMID- 29020961
TI  - Hazardous waste and health impact: a systematic review of the scientific
      literature.
AB  - : Waste is part of the agenda of the European Environment and Health Process and
      included among the topics of the Sixth Ministerial Conference on Environment and
      Health. Disposal and management of hazardous waste are worldwide challenges. We
      performed a systematic review to evaluate the evidence of the health impact of
      hazardous waste exposure, applying transparent and a priori defined methods. The
      following five steps, based on pre-defined systematic criteria, were applied. 1.
      Specify the research question, in terms of "Population-Exposure-Comparators
      Outcomes" (PECO). POPULATION: people living near hazardous waste sites; Exposure:
      exposure to hazardous waste; Comparators: all comparators; Outcomes: all
      diseases/health disorders. 2. Carry out the literature search, in Medline and
      EMBASE. 3. Select studies for inclusion: original epidemiological studies,
      published between 1999 and 2015, on populations residentially exposed to
      hazardous waste. 4. Assess the quality of selected studies, taking into account
      study design, exposure and outcome assessment, confounding control. 5. Rate the
      confidence in the body of evidence for each outcome taking into account the
      reliability of each study, the strength of the association and concordance of
      results.Fifty-seven papers of epidemiological investigations on the health status
      of populations living near hazardous waste sites were selected for the evidence
      evaluation. The association between 95 health outcomes (diseases and disorders)
      and residential exposure to hazardous waste sites was evaluated. Health effects
      of residential hazardous waste exposure, previously partially unrecognized, were
      highlighted. Sufficient evidence was found of association between exposure to oil
      industry waste that releases high concentrations of hydrogen sulphide and acute
      symptoms. The evidence of causal relationship with hazardous waste was defined as
      limited for: liver, bladder, breast and testis cancers, non-Hodgkin lymphoma,
      asthma, congenital anomalies overall and anomalies of the neural tube,
      urogenital, connective and musculoskeletal systems, low birth weight and pre-term
      birth; evidence was defined as inadequate for the other health outcomes. The
      results, although not conclusive, provide indications that more effective public
      health policies on hazardous waste management are urgently needed. International,
      national and local authorities should oppose and eliminate poor, outdated and
      illegal practices of waste disposal, including illegal transboundary trade, and
      increase support regulation and its enforcement.

PMID- 29020963
TI  - Relation of four nontraditional lipid profiles to diabetes in rural Chinese H
      type hypertension population.
AB  - BACKGROUND: Mounting evidence suggested that nontraditional lipid profiles have
      been recognized as a reliable indicator for unfavorable cardiovascular events.
      The purpose of this study was to explore the role of nontraditional lipid
      profiles as potential clinical indices for the assessment of prevalent diabetes
      in rural Chinese H-type hypertension population. METHODS: During 2012 to 2013, we
      conducted a large cross-sectional study of 2944 H-type hypertension participants
      (>=35 years of age) from rural areas in northeast China. Subjects underwent
      accurate assessment of lipid profiles, fasting plasma glucose (FPG), homocysteine
      (Hcy) according to standard protocols. RESULTS: The proportion of diabetes showed
      a graded and linear increase across the quartiles for all four nontraditional
      lipid parameters. Nontraditional lipid variables were independent determinants of
      FPG, and its correlation for TG/HDL-C was strongest, whether potential
      confounders were adjusted or not. Multivariable logistic regression analysis
      established that the highest triglycerides (TG)/ high-density lipoprotein
      cholesterol (HDL-C) quartile manifested the largest ORs of prevalent diabetes
      (OR: 3.275, 95%CI: 2.109-5.087) compared with the lowest quartile. The fully
      adjusted ORs (95%CI) were 2.753 (1.783-4.252), 2.178 (1.415-2.351), 1.648 (1.097
      2.478) for the top quartile of total cholesterol (TC)/HDL-C, low-density
      lipoprotein cholesterol (LDL-C)/HDL-C, and non-high-density lipoprotein
      cholesterol (non-HDL-C), respectively. On the basis of the area under receiver
      operating characteristic curve (AUC), TG/HDL-C showed the optimal discriminating
      power for diabetes (AUC: 0.684, 95% CI: 0.650-0.718). CONCLUSIONS: Nontraditional
      lipid profiles (TG/HDL-C, TC/HDL-C, LDL-C/HDL-C and non-HDL-C) were all
      consistently and independently correlated with prevalent diabetes among the H
      type hypertension population in rural China. TG/HDL-C was prone to be more
      profitable in assessing the risk of prevalent diabetes and should be encouraged
      as an effective clinical tool for monitoring and targeted intervention of
      diabetes in H-type hypertension adults.

PMID- 29020965
TI  - Epidemiological link of a major cholera outbreak in Greater Accra region of
      Ghana, 2014.
AB  - BACKGROUND: Cholera remains an important public health challenge globally.
      Several pandemics have occurred in different parts of the world and have been
      epidemiologically linked by different researchers to illustrate how the cases
      were spread and how they were related to index cases. Even though the risk
      factors associated with the 2014 cholera outbreak were investigated extensively,
      the link between index cases and the source of infection was not investigated to
      help break the transmission process. This study sought to show how the index
      cases from various districts of the Greater Accra Region may have been linked.
      METHODS: We carried out a descriptive cross sectional study to investigate the
      epidemiological link of the 2014 cholera outbreak in the Greater Accra region of
      Ghana. An extensive review of all district records on cholera cases in the
      Greater Accra region was carried out. Index cases were identified with the help
      of line lists. Univariate analyses were expressed as frequency distributions,
      percentages, mean +/- Standard Deviation, and rates (attack rates, case-fatality
      rates etc.) as appropriate. Maps were drawn using Arc GIS and Epi info software
      to describe the pattern of transmission. RESULTS: Up to 20,199 cholera cases were
      recorded. Sixty percent of the cases were between 20 and 40 years and about 58%
      (11,694) of the total cases were males. Almost 50% of the cases occurred in the
      Accra Metro district. Two-thirds of the index cases ate food prepared outside
      their home and had visited the Accra Metropolis. CONCLUSIONS: The 2014 cholera
      outbreak can be described as a propagated source outbreak linked to the Accra
      Metropolis. The link between index cases and the source of infection, if
      investigated earlier could have helped break the transmission process. Such
      investigations also inform decision-making about the appropriate interventions to
      be instituted to prevent subsequent outbreaks.

PMID- 29020964
TI  - IL-27 mediates HLA class I up-regulation, which can be inhibited by the IL-6
      pathway, in HLA-deficient Small Cell Lung Cancer cells.
AB  - BACKGROUND: Recently, immunotherapy with anti-PD-1 antibodies has shown clinical
      benefit in recurrent Small Cell Lung Cancer (SCLC). Since anti-PD-1 re-activates
      anti-tumor Cytotoxic T Lymphocyte (CTL) responses, it is crucial to understand
      the mechanisms regulating HLA class I, and PD-L1 expression in HLA-negative SCLC.
      Here we addressed the role of IL-27, a cytokine related to both IL-6 and IL-12
      families. METHODS: The human SCLC cell lines NCI-N592, -H69, -H146, -H446 and 
      H82 were treated in vitro with different cytokines (IL-27, IFN-gamma, IL-6 or a
      soluble IL-6R/IL-6 chimera [sIL-6R/IL-6]) at different time points and analyzed
      for tyrosine-phosphorylated STAT proteins by Western blot, for surface molecule
      expression by immunofluorescence and FACS analyses or for specific mRNA
      expression by QRT-PCR. Relative quantification of mRNAs was calculated by the
      DeltaDeltaCT method. The Student's T test was used for the statistical analysis
      of experimental replicates. RESULTS: IL-27 triggered STAT1/3 phosphorylation and
      up-regulated the expression of surface HLA class I antigen and of TAP1 and TAP2
      mRNA in four out of five SCLC cell lines tested. The IL-27-resistant NCI-H146
      cells showed up-regulation of HLA class I by IFN-gamma. IFN-gamma also induced
      expression of PD-L1 in SCLC cells, while IL-27 was less potent in this respect.
      IL-27 failed to activate STAT1/3 phosphorylation in NCI-H146 cells, which display
      a low expression of the IL-27RA and GP130 receptor chains. As GP130 is shared in
      IL-27R and IL-6R complexes, we assessed its functionality in response to sIL
      6R/IL-6. sIL-6R/IL-6 failed to trigger STAT1/3 signaling in NCI-H146 cells,
      suggesting low GP130 expression or uncoupling from signal transduction. Although
      both sIL-6R/IL-6 and IL-27 triggered STAT1/3 phosphorylation, sIL-6R/IL-6 failed
      to up-regulate HLA class I expression, in relationship to the weak activation of
      STAT1. Finally sIL-6R/IL-6 limited IL-27-effects, particularly in NCI-H69 cells,
      in a SOCS3-independent manner, but did not modify IFN-gamma induced HLA class I
      up-regulation. CONCLUSIONS: In conclusion, IL-27 is a potentially interesting
      cytokine for restoring HLA class I expression for SCLC combined immunotherapy
      purposes. However, the concomitant activation of the IL-6 pathway may limit the
      IL-27 effect on HLA class I induction but did not significantly alter the
      responsiveness to IFN-gamma.

PMID- 29020966
TI  - Methods used in prevalence studies of disrespect and abuse during facility based
      childbirth: lessons learned.
AB  - BACKGROUND: Several recent studies have attempted to measure the prevalence of
      disrespect and abuse (D&A) of women during childbirth in health facilities.
      Variations in reported prevalence may be associated with differences in study
      instruments and data collection methods. This systematic review and comparative
      analysis of methods aims to aggregate and present lessons learned from published
      studies that quantified the prevalence of Disrespect and Abuse (D&A) during
      childbirth. METHODS: We conducted a systematic review of the literature in
      accordance with PRISMA (Preferred Reporting Items for Systematic Review and Meta
      Analysis) guidelines. Five papers met criteria and were included for analysis. We
      developed an analytical framework depicting the basic elements of epidemiological
      methodology in prevalence studies and a table of common types of systematic error
      associated with each of them. We performed a head-to-head comparison of study
      methods for all five papers. Using these tools, an independent reviewer provided
      an analysis of the potential for systematic error in the reported prevalence
      estimates. RESULTS: Sampling techniques, eligibility criteria, categories of D&A
      selected for study, operational definitions of D&A, summary measures of D&A, and
      the mode, timing, and setting of data collection all varied in the five studies
      included in the review. These variations present opportunities for the
      introduction of biases - in particular selection, courtesy, and recall bias - and
      challenge the ability to draw comparisons across the studies' results.
      CONCLUSION: Our review underscores the need for caution in interpreting or
      comparing previously reported prevalence estimates of D&A during facility-based
      childbirth. The lack of standardized definitions, instruments, and study methods
      used to date in studies designed to quantify D&A in childbirth facilities
      introduced the potential for systematic error in reported prevalence estimates,
      and affected their generalizability and comparability. Chief among the lessons to
      emerge from comparing methods for measuring the prevalence of D&A is recognition
      of the tension between seeking prevalence measures that are reliable and
      generalizable, and attempting to avoid loss of validity in the context where the
      issue is being studied.

PMID- 29020967
TI  - An updated meta-analysis of the asporin gene D-repeat in knee osteoarthritis:
      effects of gender and ethnicity.
AB  - BACKGROUND: Knee osteoarthritis (KOA) is the most prevalent form of knee joint
      disease and characterized by the progressive degeneration of articular cartilage.
      Although pathology of KOA remains unknown, genetic factors are considered to be
      the major cause. Asporin is a group of biologically active components of
      extracellular matrix (ECM) in articular cartilage, and asporin gene (ASPN) D
      repeat polymorphism was reported to be associated with KOA. Thus, our meta
      analysis is aimed at investigation of the association between asporin D-repeat
      polymorphism and susceptibility of KOA. METHODS: We gathered data from MEDLINE,
      Embase, OVID, and ScienceDirect to search relevant published epidemiological
      studies through April 2017. Compared with previous studies, our meta-analysis is
      the first study to investigate the association of ASPN D15, D16, and D17 alleles
      and KOA susceptibility by ethnic- and sex-stratified subgroup analysis. RESULTS:
      We found no significant association between D15 allele and susceptibility to KOA
      (OR = 1.05, 95% CI 0.95-1.17) in overall population. The same results were
      observed in the analysis of D16 (OR = 1.01, 95% CI 0.80-1.28) and D17 alleles (OR
      = 1.28, 95% CI 0.91-1.80). The ethnic- and sex-subgroup analyses did not alter
      the ORs. However, significant association was detected in the sensitivity
      analysis of D17 in overall population (OR = 1.05, 95% CI 0.95-1.17) and Asian
      population (OR = 1.78, 95% CI 1.02-3.11, P < 0.05). CONCLUSION: Our results
      indicated that D-repeat polymorphism of ASPN may not play a major role in
      susceptibility of KOA in ethnic- and sex-specific analysis. Because of the
      limitations of the present meta-analysis, firm conclusions could not be drawn
      based on the current evidence, and further studies are required to detect genuine
      role of ASPN.

PMID- 29020968
TI  - Robot-assisted assessment of muscle strength.
AB  - Impairment of neuromuscular function in neurological disorders leads to
      reductions in muscle force, which may lower quality of life. Rehabilitation
      robots that are equipped with sensors are able to quantify the extent of muscle
      force impairment and to monitor a patient during the process of
      neurorehabilitation with sensitive and objective assessment methods. In this
      article, we provide an overview of fundamental aspects of muscle function and how
      the corresponding variables can be quantified by means of meaningful robotic
      assessments that are primarily oriented towards upper limb neurorehabilitation.
      We discuss new concepts for the assessment of muscle function, and present an
      overview of the currently available systems for upper limb measurements. These
      considerations culminate in practical recommendations and caveats for the
      rational quantification of force magnitude, force direction, moment of a force,
      impulse, critical force (neuromuscular fatigue threshold) and state and trait
      levels of fatigue.

PMID- 29020969
TI  - Updates on cardiovascular outcome trials in diabetes.
AB  - In 2008 the Food and Drug Administration introduced a guidance for industry that
      requires the investigation of cardiovascular outcomes of glucose-lowering
      medications. Since then, an increasing number of cardiovascular outcome trials
      have been completed in diabetes patients with high cardiovascular risk for
      members of the SGLT-2 and DPP4 inhibitors and GLP-1 receptor agonist classes. The
      trials confirmed cardiovascular safety for all tested anti-hyperglycaemic drugs
      and, in addition empagliflozin, semaglutide and liraglutide could even reduce
      cardiovascular risk. The present review summarizes the results of the DEVOTE,
      CANVAS, EXSCEL and ACE trials that tested cardiovascular safety of Insulin
      degludec, canagliflozin, once-weekly exenatide and acarbose and were published in
      2017. We provide context on these results by comparing them with earlier trials
      of glucose-lowering drugs and give an outlook on what to expect in coming years.

PMID- 29020970
TI  - Informing new or improved vector control tools for reducing the malaria burden in
      Tanzania: a qualitative exploration of perceptions of mosquitoes and methods for
      their control among the residents of Dar es Salaam.
AB  - BACKGROUND: The effectiveness of malaria prevention with long-lasting
      insecticidal nets and indoor residual spraying is limited by emerging insecticide
      resistance, evasive mosquito behaviours that include outdoor biting, sub-optimal
      implementation and inappropriate use. New vector control interventions are
      required and their potential effectiveness will be enhanced if existing household
      perceptions and practices are integrated into intervention design. METHODS: This
      qualitative descriptive study used focus groups discussions, in-depth interviews
      and photovoice methods to explore mosquito control perceptions and practices
      among residents in four study sites in Dar es Salaam, Tanzania. RESULTS:
      Mosquitoes were perceived as a growing problem, directly attributed to widespread
      environmental deterioration and lack of effective mosquito control interventions.
      Malaria and nuisance biting were perceived as the main problem caused by
      mosquitoes. Breeding sites were clearly distinguished from resting sites but
      residents did not differentiate between habitats producing malaria vector
      mosquitoes and others producing mostly nuisance mosquitoes. The most frequently
      mentioned protection methods in the wealthiest locations were bed nets, aerosol
      insecticide sprays, window screens, and fumigation, while bed nets were most
      frequently mentioned and described as 'part of the culture' in the least wealthy
      locations. Mosquito-proofed housing was consistently viewed as desirable, but
      considered unaffordable outside wealthiest locations. Slapping and covering up
      with clothing were most commonly used to prevent biting outdoors. Despite their
      utility outdoors, topical repellents applied to the skin were considered
      expensive, and viewed with suspicion due to perceived side effects. Improving the
      local environment was the preferred method for preventing outdoor biting.
      Affordability, effectiveness, availability, practicality, as well as social
      influences, such as government recommendations, socialization and internalization
      (familiarization and habit) were described as key factors influencing uptake.
      CONCLUSIONS: Outdoor transmission is widely accepted as an obstacle to malaria
      elimination. Larval source management, targeting both malaria vectors and
      nuisance-biting mosquitoes, is the preferred method for mosquito control among
      the residents of Dar es Salaam and should be prioritized for development
      alongside new methods for outdoor personal protection. Even if made available,
      effective and affordable, these additional interventions may require time and
      user experience to achieve positive reputations and trustworthiness.

PMID- 29020971
TI  - Efficacy and safety of turmeric and curcumin in lowering blood lipid levels in
      patients with cardiovascular risk factors: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Dyslipidemia is an important and common cardiovascular risk factor in
      the general population. The lipid-lowering effects of turmeric and curcumin are
      unconfirmed. We performed a meta-analysis to assess the efficacy and safety of
      turmeric and curcumin in lowering blood lipids in patients at risk of
      cardiovascular disease (CVD). METHODS: A comprehensive literature search was
      conducted on PubMed, Embase, Ovid, Medline and Cochrane Library databases to
      identify randomized controlled trials (published as of November 2016) that
      assessed the effect of turmeric and curcumin on blood lipid levels including
      total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density
      lipoprotein cholesterol (HDL-C), and triglycerides (TG). Pooled standardized mean
      difference (SMD) with 95% confidence interval (CI) was used to assess the effect.
      RESULTS: The analysis included 7 eligible studies (649 patients). Turmeric and
      curcumin significantly reduced serum LDL-C (SMD = -0.340, 95% confidence interval
      [CI]: -0.530 to -0.150, P < 0.0001) and TG (SMD = -0.214, 95% CI: -0.369 to 
      0.059, P = 0.007) levels as compared to those in the control group. These may be
      effective in lowering serum TC levels in patients with metabolic syndrome (MetS,
      SMD = -0.934, 95% CI: -1.289 to -0.579, P < 0.0001), and turmeric extract could
      possibly have a greater effect on reducing serum TC levels (SMD = -0.584, 95% CI:
      -0.980 to -0.188, P = 0.004); however, the efficacy is yet to be confirmed. Serum
      HDL-C levels were not obviously improved. Turmeric and curcumin appeared safe,
      and no serious adverse events were reported in any of the included studies.
      CONCLUSIONS: Turmeric and curcumin may protect patients at risk of CVD through
      improving serum lipid levels. Curcumin may be used as a well-tolerated dietary
      adjunct to conventional drugs. Further research is required to resolve
      uncertainties related to dosage form, dose and medication frequency of curcumin.

PMID- 29020974
TI  - Interventions to reduce dependency in bathing in community dwelling older adults:
      a systematic review.
AB  - BACKGROUND: The onset of bathing disability for older adults has been found to be
      an indicator and potential precursor of further disability. Thus interventions
      targeting bathing may prevent or delay further disability and the use of health
      and social care services. The aim of this systematic review was to identify
      interventions targeted at reducing dependency in bathing for community dwelling
      older adults, and determine their content and effectiveness in maintaining or
      improving function and quality of life. METHODS: We conducted a systematic search
      of electronic databases including: The Cochrane Central Register of Controlled
      Trials (CENTRAL); MEDLINE; EMBASE; AMED; CINAHL; PsycINFO and OTSeeker. The
      search took place on 18 October 2016. We included randomised controlled trials,
      nonrandomised controlled trials, and controlled before and after studies that
      evaluated an intervention designed to reduce dependency in bathing. Articles were
      screened for inclusion by two independent reviewers; risk of bias was assessed
      using quality assessment tools; and data extracted using pre-prepared forms.
      Disagreements were resolved by discussion and inclusion of a third reviewer.
      RESULTS: The search process identified one study for inclusion in the review.
      This study evaluated a bathing intervention delivered by an occupational
      therapist following discharge from hospital. Overall, the findings suggest modest
      improvements in functional ability in favour of the intervention group although
      the results should be interpreted with caution. CONCLUSION: Despite evidence
      suggesting the importance of addressing bathing difficulties as a means of
      possible prevention of disability in the ageing process, there is a dearth of
      evaluative or interventional research studies. Further robust research is
      warranted, including studies of randomised and controlled design.

PMID- 29020972
TI  - SUMO1 modification of KHSRP regulates tumorigenesis by preventing the TL-G-Rich
      miRNA biogenesis.
AB  - BACKGROUND: MicroRNAs (miRNAs) are important regulators involved in diverse
      physiological and pathological processes including cancer. SUMO (small ubiquitin
      like modifier) is a reversible protein modifier. We recently found that
      SUMOylation of TARBP2 and DGCR8 is involved in the regulation of the miRNA
      pathway. KHSRP is a single stranded nucleic acid binding protein with roles in
      transcription and mRNA decay, and it is also a component of the Drosha-DGCR8
      complex promoting the miRNA biogenesis. METHODS: The in vivo SUMOylation assay
      using the Ni2+-NTA affinity pulldown or immunoprecipitation (IP) and the in vitro
      E.coli-based SUMOylation assay were used to analyze SUMOylation of KHSRP.
      Nuclear/Cytosol fractionation assay and immunofluorescent staining were used to
      observe the localization of KHSRP. High-throughput miRNA sequencing, quantantive
      RT-PCR and RNA immunoprecipitation assay (RIP) were employed to determine the
      effects of KHSRP SUMO1 modification on the miRNA biogenesis. The soft-agar colony
      formation, migration, vasculogenic mimicry (VM) and three-dimensional (3D) cell
      culture assays were performed to detect the phenotypes of tumor cells in vitro,
      and the xenograft tumor model in mice was conducted to verify that SUMO1
      modification of KHSRP regulated tumorigenesis in vivo. RESULTS: KHSRP is modified
      by SUMO1 at the major site K87, and this modification can be increased upon the
      microenvironmental hypoxia while reduced by the treatment with growth factors.
      SUMO1 modification of KHSRP inhibits its interaction with the pri-miRNA/Drosha
      DGCR8 complex and probably increases its translocation from the nucleus to the
      cytoplasm. Consequently, SUMO1 modification of KHSRP impairs the processing step
      of pre-miRNAs from pri-miRNAs which especially harbor short G-rich stretches in
      their terminal loops (TL), resulting in the downregulation of a subset of TL-G
      Rich miRNAs such as let-7 family and consequential tumorigenesis. CONCLUSIONS:
      Our data demonstrate how the miRNA biogenesis pathway is connected to
      tumorigenesis and cancer progression through the reversible SUMO1 modification of
      KHSRP.

PMID- 29020973
TI  - The alpha-melanocyte stimulating hormone/peroxisome proliferator activated
      receptor-gamma pathway down-regulates proliferation in melanoma cell lines.
AB  - BACKGROUND: The alpha-Melanocyte Stimulating Hormone (alphaMSH)/Melanocortin-1
      receptor (MC1R) interaction promotes melanogenesis through the cAMP/PKA pathway.
      The direct induction of this pathway by Forskolin (FSK) is also known to enhance
      melanocyte proliferation. alphaMSH acts as a mitogenic agent in melanocytes and
      its effect on proliferation of melanoma cells is less known. We previously
      identified the alphaMSH/Peroxisome Proliferator Activated Receptor (PPARgamma)
      pathway as a new pathway on the B16-F10 mouse melanoma cell line. alphaMSH
      induced the translocation of PPARgamma into the nucleus as an active
      transcription factor. This effect was independent of the cAMP/PKA pathway and was
      mediated by the activation of the PI(4,5)P2/PLC pathway, a pathway which we have
      described to be triggered by the alphaMSH-dependent MC1R stimulation. Moreover,
      in the same study, preliminary experiments showed that mouse melanoma cells
      responded to alphaMSH by reducing proliferation and that PPARgamma was involved
      in this effect. Due to its key role in the control of cell proliferation,
      PPARgamma agonists are used in therapeutic models for different forms of cancer,
      including melanoma. The purpose of this study was: (a) to confirm the different
      proliferative behavior in response to alphaMSH in healthy and in melanoma
      condition; (b) to verify whether the cAMP/PKA pathway and the PLC/PPARgamma
      pathway could exert an antagonistic function in the control of proliferation; (c)
      to deepen the knowledge of the molecular basis responsible for the down
      proliferative response of melanoma cells after exposure to alphaMSH. METHODS: We
      employed B16-F10 cell line, a human melanoma cell line (Mel 13) and two primary
      cultures of human melanocytes (NHM 1 and NHM 2, respectively), all expressing a
      wild type MC1R and responding to the alphaMSH in terms of pigmentation. We
      evaluated cell proliferation through: a) cell counting, b) cell cycle analysis c)
      protein expression of proliferation modulators (p27, p21, cyclin D1 and cyclin
      E). RESULTS: The alphaMSH acted as a mitogenic agent in primary cultures of human
      melanocytes, whereas it determined a slow down of proliferation in melanoma cell
      lines. FSK, as an inducer of the cAMP/PKA pathway, reproduced the alphaMSH
      mediated effect on proliferation in NHMs but it did not mimic the alphaMSH effect
      on proliferation in B16-F10 and Mel 13 melanoma cell lines. Meanwhile, 3 M3-FBS
      (3 M3), as an inducer of PI(4,5)P2/PLC pathway, reproduced the alphaMSH
      proliferative effect. Further experiments, treating melanoma cell lines with
      alphaMSH in the presence/absence of GW9662, as an inhibitor of PPARgamma,
      confirmed the key role of this transcription factor in decreasing cell
      proliferation in response to the hormone exposure. CONCLUSIONS: In both melanoma
      cell lines, alphaMSH determined the reduction of proliferation through the
      PI(4,5)P2/PLC pathway, employing PPARgamma as an effector element. These evidence
      could offer perspectives for new therapeutic approaches for melanoma.

PMID- 29020975
TI  - Workforce planning-going beyond the count.
AB  - Every country struggles with how best to meet the demand for health care services
      with the available resources. This commentary offers a perspective on the Israeli
      physician workforce and the analyses of Horowitz et al., which found age and
      gender differences in physician productivity and career longevity, differences
      across specialties, and a sizeable fraction of licensed Israeli physicians living
      abroad. Workforce planning can be subject to data collection and statistical
      uncertainties, but even more important are the assumptions and forecasts related
      to demand for services and organizational arrangements for care delivery. Readers
      should be cautious in analyzing productivity just by counting hours or years
      worked, and comparisons across countries may not account for differences in the
      nature of physician work. The question of whether Israel has enough physicians
      for the future has to go "beyond the count" to looking at the roles of other
      health professionals, the use of new technologies and new team configurations,
      and the overall efficiency and effectiveness of health care delivery systems such
      as hospitals, ambulatory care clinics, and community-based care.

PMID- 29020977
TI  - Platelet-rich plasma stimulates angiogenesis in mice which may promote hair
      growth.
AB  - BACKGROUND: Platelet-rich plasma (PRP) is an autologous concentration of human
      platelets in plasma. In this paper, we aimed to investigate the effect of PRP on
      hair growth. METHODS: Platelet-rich plasma and platelet-poor plasma were prepared
      by sterile centrifugation and injected into shaved dorsal skin of mice (n = 10).
      Saline injection was used in the control group. The length of randomly plucked
      hairs was measured at 8, 13, 18 days after PRP injection. Histological
      examination was preformed to observe the histologic changes of skins. The
      immunohistochemistry analysis of CD31 was performed to detect the changes of hair
      length and formation of new vessels. RESULTS: At 13 and 18 days after the last
      injection, the hair length of mice in PRP group (4.24 +/- 0.60 and 8.29 +/- 0.48
      mm, respectively) was significantly longer compared with the control group (3.70
      +/- 0.52 and 7.21 +/- 0.64 mm, p < 0.05). No significant difference in the hair
      length was found between the PPP group and the control (p > 0.05). In addition,
      the number of CD31-positive vessel in the PRP group (9.90 +/- 0.60) was more than
      that in the control group (8.60 +/- 2.34, p < 0.05). CONCLUSION: Platelet-rich
      plasma might promote hair length growth and increase the number of hair follicles
      by inducing angiogenesis.

PMID- 29020978
TI  - Precision medicine at the crossroads.
AB  - There are bioethical, institutional, economic, legal, and cultural obstacles to
      creating the robust-precompetitive-data resource that will be required to advance
      the vision of "precision medicine," the ability to use molecular data to target
      therapies to patients for whom they offer the most benefit at the least risk.
      Creation of such an "information commons" was the central recommendation of the
      2011 report Toward Precision Medicine issued by a committee of the National
      Research Council of the USA (Committee on a Framework for Development of a New
      Taxonomy of Disease; National Research Council. Toward precision medicine:
      building a knowledge network for biomedical research and a new taxonomy of
      disease. 2011). In this commentary, I review the rationale for creating an
      information commons and the obstacles to doing so; then, I endorse a path forward
      based on the dynamic consent of research subjects interacting with researchers
      through trusted mediators. I assert that the advantages of the proposed system
      overwhelm alternative ways of handling data on the phenotypes, genotypes, and
      environmental exposures of individual humans; hence, I argue that its creation
      should be the central policy objective of early efforts to make precision
      medicine a reality.

PMID- 29020976
TI  - The added value of a mobile application of Community Case Management on referral,
      re-consultation and hospitalization rates of children aged under 5 years in two
      districts in Northern Malawi: study protocol for a pragmatic, stepped-wedge
      cluster-randomized controlled trial.
AB  - BACKGROUND: There is evidence to suggest that frontline community health workers
      in Malawi are under-referring children to higher-level facilities. Integrating a
      digitized version of paper-based methods of Community Case Management (CCM) could
      strengthen delivery, increasing urgent referral rates and preventing unnecessary
      re-consultations and hospital admissions. This trial aims to evaluate the added
      value of the Supporting LIFE electronic Community Case Management Application (SL
      eCCM App) compared to paper-based CCM on urgent referral, re-consultation and
      hospitalization rates, in two districts in Northern Malawi. METHODS/DESIGN: This
      is a pragmatic, stepped-wedge cluster-randomized trial assessing the added value
      of the SL eCCM App on urgent referral, re-consultation and hospitalization rates
      of children aged 2 months and older to up to 5 years, within 7 days of the index
      visit. One hundred and two health surveillance assistants (HSAs) were stratified
      into six clusters based on geographical location, and clusters randomized to the
      timing of crossover to the intervention using simple, computer-generated
      randomization. Training workshops were conducted prior to the control (paper-CCM)
      and intervention (paper-CCM + SL eCCM App) in assigned clusters. Neither
      participants nor study personnel were blinded to allocation. Outcome measures
      were determined by abstraction of clinical data from patient records 2 weeks
      after recruitment. A nested qualitative study explored perceptions of adherence
      to urgent referral recommendations and a cost evaluation determined the financial
      and time-related costs to caregivers of subsequent health care utilization. The
      trial was conducted between July 2016 and February 2017. DISCUSSION: This is the
      first large-scale trial evaluating the value of adding a mobile application of
      CCM to the assessment of children aged under 5 years. The trial will generate
      evidence on the potential use of mobile health for CCM in Malawi, and more widely
      in other low- and middle-income countries. TRIAL REGISTRATION:
      ClinicalTrials.gov, ID: NCT02763345 . Registered on 3 May 2016.

PMID- 29020979
TI  - Perfectly matched 20-nucleotide guide RNA sequences enable robust genome editing
      using high-fidelity SpCas9 nucleases.
AB  - High-fidelity SpCas9 variants (eSpCas9 and SpCas9-HF1) have been engineered to
      reduce off-target effects. We found that changes in guide RNA length induced
      significant reductions in the editing activities of SpCas9 variants in plant
      cells. Single guide RNAs harboring precise, perfectly matched 20-nucleotide guide
      sequences are necessary for high on-target editing activities of eSpCas9 and
      SpCas9-HF1. Precise 20-nucleotide guide sequences derived from tRNA-sgRNA
      precursors enable robust on-target editing by these variants with enhanced
      specificity. Our work reveals an effective way of enhancing the use of the high
      fidelity SpCas9 nucleases for efficient and precise genome engineering.

PMID- 29020981
TI  - Areas with evidence of equity and their progress on mortality from tuberculosis
      in an endemic municipality of southeast Brazil.
AB  - BACKGROUND: In Brazil, people still fall ill and die from tuberculosis (TB), and
      this can be explained by the significant impasse in the equity of distribution of
      therapeutic resources to the population as a whole. The aim was to identify
      geographical areas which have shown progress in terms of equity (of income,
      schooling and urban occupancy) and test its effect on mortality from TB in a
      municipality of southeast Brazil. METHODS: It is an ecological study considering
      TB as the basic cause for deaths registered between 2006 and 2013 on the
      Mortality Information System and other variables obtained through the Demographic
      Census of the Brazilian Institute of Geography and Statistics (2010). The
      geographical area for analysis comprised the areas of coverage of the health
      services. Social indicators have been constructed through the Principal Component
      Analysis (PCA). The cases were geocoded and the annual mortality rate from TB was
      calculated with smoothing using the local empirical Bayesian method. Multiple
      linear regression was then performed. There was confirmation of the existence of
      spatial dependence of residue through the application of the Global Moran I test,
      and application of the Models with Global Spatial Effects, to identify the best
      standard of spatial regression. RESULTS: The mortality rates ranged from 0.00 to
      2.8 deaths per 100,000 people, per year. In the PCA, three indicators were
      constructed, and designated as indicators of income, social inequality, and
      social equity. In multiple linear regression, the indicator of social equity was
      statistically significant (P < 0.0001) but had a negative association, an
      adjusted R2 of 28.36% and with spatial dependence (Moran I = 0.21, P = 0.003455).
      The best model to deal with existing spatial dependence was the Spatial Lag
      Model. CONCLUSIONS: The better social conditions have shown progress in reducing
      mortality from TB, thereby reinforcing the achievement of Sustainable Development
      Goals. In addition, cartography was also applied, which can be replicated in
      other scenarios throughout the world, using a scope distinct from that of works
      traditionally produced in that it places the emphasis on social equity.

PMID- 29020980
TI  - Identification of 76 novel B1 metallo-beta-lactamases through large-scale
      screening of genomic and metagenomic data.
AB  - BACKGROUND: Metallo-beta-lactamases are bacterial enzymes that provide resistance
      to carbapenems, the most potent class of antibiotics. These enzymes are commonly
      encoded on mobile genetic elements, which, together with their broad substrate
      spectrum and lack of clinically useful inhibitors, make them a particularly
      problematic class of antibiotic resistance determinants. We hypothesized that
      there is a large and unexplored reservoir of unknown metallo-beta-lactamases,
      some of which may spread to pathogens, thereby threatening public health. The aim
      of this study was to identify novel metallo-beta-lactamases of class B1, the most
      clinically important subclass of these enzymes. RESULTS: Based on a new
      computational method using an optimized hidden Markov model, we analyzed over
      10,000 bacterial genomes and plasmids together with more than 5 terabases of
      metagenomic data to identify novel metallo-beta-lactamase genes. In total, 76
      novel genes were predicted, forming 59 previously undescribed metallo-beta
      lactamase gene families. The ability to hydrolyze imipenem in an Escherichia coli
      host was experimentally confirmed for 18 of the 21 tested genes. Two of the novel
      B1 metallo-beta-lactamase genes contained atypical zinc-binding motifs in their
      active sites, which were previously undescribed for metallo-beta-lactamases.
      Phylogenetic analysis showed that B1 metallo-beta-lactamases could be divided
      into five major groups based on their evolutionary origin. Our results also show
      that, except for one, all of the previously characterized mobile B1 beta
      lactamases are likely to have originated from chromosomal genes present in
      Shewanella spp. and other Proteobacterial species. CONCLUSIONS: This study more
      than doubles the number of known B1 metallo-beta-lactamases. The findings have
      further elucidated the diversity and evolutionary history of this important class
      of antibiotic resistance genes and prepare us for some of the challenges that may
      be faced in clinics in the future.

PMID- 29020982
TI  - The prognostic value of C-X-C motif chemokine receptor 4 in patients with
      sporadic malignant peripheral nerve sheath tumors.
AB  - BACKGROUND: Recent studies indicate that C-X-C motif chemokine receptor 4 (CXCR4)
      and its ligand, C-X-C motif chemokine ligand 12 (CXCL12), stimulate expression of
      the cell cycle regulatory protein Cyclin D1 in neurofibromatosis 1-associated
      malignant peripheral nerve sheath tumor (MPNST) cells and promote their
      proliferation. In this study, we measured the expression of CXCR4, CXCL12, and
      Cyclin D1 proteins in sporadic MPNST tissues from Chinese patients and
      investigated their prognostic values. METHODS: CXCR4, CXCL12, and Cyclin D1
      protein expression in samples from 58 Chinese patients with sporadic MPNST was
      assessed with immunohistochemical staining. Their prognostic values were
      evaluated with Kaplan-Meier analysis and a log-rank test. Multivariate Cox
      regression analysis was used to identify independent prognostic factors. RESULTS:
      High expression of CXCR4, CXCL12, and Cyclin D1 was observed in 19 (32.8%), 32
      (55.2%), and 16 (27.6%) samples, respectively. CXCR4 expression was positively
      correlated with CXCL12 expression (r = 0.334, P = 0.010) and Cyclin D1 expression
      (r = 0.309, P = 0.018). Patients with high CXCR4 expression showed longer overall
      survival than those with low CXCR4 expression (chi2 = 4.642, P = 0.031).
      CONCLUSION: High CXCR4 expression may define a specific subtype of sporadic MPNST
      with favorable prognosis.

PMID- 29020983
TI  - CXCR2 Inhibition - a novel approach to treating CoronAry heart DiseAse (CICADA):
      study protocol for a randomised controlled trial.
AB  - BACKGROUND: There is emerging evidence of the central role of neutrophils in both
      atherosclerotic plaque formation and rupture. Patients with lower neutrophil
      counts following acute coronary syndromes tend to have a greater coronary flow
      reserve, which is a strong predictor of long-term cardiovascular health. But so
      far, no data are available regarding the impact of neutrophil inhibition on
      cardiovascular clinical or surrogate endpoints. Therefore, the aim of this study
      is to investigate the effects of AZD5069, a cysteine-X-cysteine chemokine
      receptor 2 (CXCR2) inhibitor, on coronary flow reserve and coronary structure and
      function in patients with coronary artery disease. METHODS/DESIGN: Ninety
      subjects with coronary artery disease undergoing percutaneous coronary
      intervention will be included in this investigator-driven, randomised, placebo
      controlled, double-blind, phase IIa, single-centre study. Participants will be
      randomised to receive either AZD5069 (40 mg) administered orally twice daily or
      placebo for 24 weeks. Change in coronary flow reserve as determined by 13N
      ammonia positron emission tomography-computed tomography will be the primary
      outcome. Change in the inflammatory component of coronary plaque structure and
      the backward expansion wave, an invasive coronary physiological measure of
      diastolic function, will be assessed as secondary outcomes. DISCUSSION:
      Cardiovascular surrogate parameters, such as coronary flow reserve, may provide
      insights into the potential mechanisms of the cardiovascular effects of CXCR2
      inhibitors. Currently, ongoing trials do not specifically focus on neutrophil
      function as a target of intervention, and we therefore believe that our study
      will contribute to a better understanding of the role of neutrophil-mediated
      inflammation in coronary artery disease. TRIAL REGISTRATION: EudraCT, 2016-000775
      24 . Registered on 22 July 2016. International Standard Randomised Controlled
      Trial Number, ISRCTN48328178 . Registered on 25 February 2016.

PMID- 29020984
TI  - Fully digital data processing during cardiovascular implantable electronic device
      follow-up in a high-volume tertiary center.
AB  - BACKGROUND: Increasing numbers of patients with cardiovascular implantable
      electronic devices (CIEDs) and limited follow-up capacities highlight unmet
      challenges in clinical electrophysiology. Integrated software (MediConnect(r))
      enabling fully digital processing of device interrogation data has been
      commercially developed to facilitate follow-up visits. We sought to assess
      feasibility of fully digital data processing (FDDP) during ambulatory device
      follow-up in a high-volume tertiary hospital to provide guidance for future users
      of FDDP software. METHODS: A total of 391 patients (mean age, 70 years)
      presenting to the outpatient department for routine device follow-up were
      analyzed (pacemaker, 44%; implantable cardioverter defibrillator, 39%; cardiac
      resynchronization therapy device, 16%). RESULTS: Quality of data transfer and
      follow-up duration were compared between digital (n = 265) and manual processing
      of device data (n = 126). Digital data import was successful, complete and
      correct in 82% of cases when early software versions were used. When using the
      most recent software version the rate of successful digital data import increased
      to 100%. Software-based import of interrogation data was complete and without
      failure in 97% of cases. The mean duration of a follow-up visit did not differ
      between the two groups (digital 18.7 min vs. manual data transfer 18.2 min).
      CONCLUSIONS: FDDP software was successfully implemented into the ambulatory
      follow-up of patients with implanted pacemakers and defibrillators. Digital data
      import into electronic patient management software was feasible and supported the
      physician's workflow. The total duration of follow-up visits comprising technical
      device interrogation and clinical actions was not affected in the present
      tertiary center outpatient cohort.

PMID- 29020985
TI  - Olfactory sensory axons target specific protoglomeruli in the olfactory bulb of
      zebrafish.
AB  - BACKGROUND: The axons of Olfactory Sensory Neurons (OSNs) project to reproducible
      target locations within the Olfactory Bulb (OB), converting odorant experience
      into a spatial map of neural activity. We characterized the initial targeting of
      OSN axons in the zebrafish, a model system suitable for studying axonal targeting
      early in development. In this system the initial targets of OSN axons are a small
      number of distinct, individually identifiable neuropilar regions called
      protoglomeruli. Previously, Olfactory Marker Protein-expressing and TRPC2
      expressing classes of OSNs were shown to project to specific, non-overlapping
      sets of protoglomeruli, indicating that particular subsets of OSNs project to
      specific protoglomerular targets. We set out to map the relationship between the
      classical Odorant Receptor (OR) an OSN chooses to express and the protoglomerulus
      its axon targets. METHODS: A panel of BACs were recombineered so that the axons
      of OSNs choosing to express modified ORs were fluorescently labeled. Axon
      projections were followed into the olfactory bulb to determine the protoglomeruli
      in which they terminated. RESULTS: RNA-seq demonstrates that OSNs express a
      surprisingly wide variety of ORs and Trace Amine Associated Receptors (TAARs)
      very early when sensory axons are arriving in the bulb. Only a single OR is
      expressed in any given OSN even at these early developmental times. We used a BAC
      expression technique to map the trajectories of OSNs expressing specific odorant
      receptors. ORs can be divided into three clades based upon their sequence
      similarities. OSNs expressing ORs from two of these clades project to the CZ
      protoglomerulus, while OSNs expressing ORs from the third clade project to the DZ
      protoglomerulus. In contrast, OSNs expressing a particular TAAR project to
      multiple protoglomeruli. Neither OR choice nor axonal targeting are related to
      the position an OSN occupies within the olfactory pit. CONCLUSIONS: Our results
      demonstrate that it is not the choice of a particular OR, but of one from a
      category of ORs, that is related to initial OSN target location within the
      olfactory bulb. These choices are not related to OSN position within the
      olfactory epithelium.

PMID- 29020986
TI  - Colorectal cancer-infiltrating T lymphocytes display a distinct chemokine
      receptor expression profile.
AB  - BACKGROUND: T lymphocytes exert important homeostatic functions in the healthy
      intestinal mucosa, whereas in case of colorectal cancer (CRC), infiltration of T
      lymphocytes into the tumor is crucial for an effective anti-tumor immune
      response. In both situations, the recruitment mechanisms of T lymphocytes into
      the tissues are essential for the immunological functions deciding the outcome.
      The recruitment of T lymphocytes is largely dependent on their expression of
      various chemokine receptors. The aim of this study was to identify potential
      chemokine receptors involved in the recruitment of T lymphocytes to normal human
      colonic mucosa and to CRC tissue, respectively, by examining the expression of 16
      different chemokine receptors on T lymphocytes isolated from these tissues.
      METHODS: Tissues were collected from patients undergoing bowel resection for CRC.
      Lymphocytes were isolated through enzymatic tissue degradation of CRC tissue and
      nearby located unaffected mucosa, respectively. The expression of a broad panel
      of chemokine receptors on the freshly isolated T lymphocytes was examined by flow
      cytometry. RESULTS: In the normal colonic mucosa, the frequencies of cells
      expressing CCR2, CCR4, CXCR3, and CXCR6 differed significantly between CD4+ and
      CD8+ T lymphocytes, suggesting that the molecular mechanisms mediating T
      lymphocyte recruitment to the gut differ between CD4+ and CD8+ T lymphocytes. In
      CRC, the frequencies of cells expressing CCR2 and CXCR5 were significantly lower
      in both the CD4+ and CD8+ T lymphocyte populations compared to unaffected colonic
      mucosa, and the frequency of CCR9+ cytotoxic T lymphocytes was significantly
      decreased in CRC tissue. CONCLUSIONS: With regard to the normal gut mucosa, the
      results suggest that the molecular mechanisms mediating T lymphocyte recruitment
      differ between CD4+ and CD8+ T lymphocytes, which are important for understanding
      gut homeostasis. Importantly, T lymphocytes from CRC compared to normal colonic
      tissue displayed a distinct chemokine receptor expression profile, suggesting
      that mechanisms for recruitment of T lymphocytes to CRC tissue are skewed
      compared to normal colonic mucosa. Understanding these mechanisms could help in
      developing new strategies in cancer immunotherapy and to optimize already
      available alternatives such as immune checkpoint inhibitors.

PMID- 29020987
TI  - SHCBP1 promotes synovial sarcoma cell metastasis via targeting TGF-beta1/Smad
      signaling pathway and is associated with poor prognosis.
AB  - BACKGROUND: Our previous studies reported that SHC SH2-domain binding protein 1
      (SHCBP1) functions as an oncogene via promoting cell proliferations in synovial
      sarcoma (SS) cells. However, whether SHCBP1 has any effect on tumor metastasis
      remains unexplored. METHODS: The expression of SHCBP1 was analyzed in 76 SS
      tissues and two SS cell lines by immunohistochemistry and real-time RT-PCR. The
      relationship between SHCBP1 expression and the clinicopathological features of SS
      was investigated. The role of SHCBP1 in SS cell adhesion, migration, invasion and
      angiogenesis was explored by adhesion, Wound healing, Transwell, and Matrigel
      tube formation assays. Western blotting was conducted to detect the protein
      expressions of TGF-beta1/Smad signaling pathway and EMT-related markers. The key
      molecules associated with migration, invasion and EMT were evaluated by
      immunohistochemistry in tumor specimens. RESULTS: In current study, we
      demonstrated that SHCBP1 overexpression significantly enhanced adhesion,
      migration, invasion and angiogenesis of SS cells. In contrast, SHCBP1 knockdown
      elicited the opposite effects on these phenotypes in vitro. SHCBP1 promoted tumor
      metastasis through inducing epithelial-mesenchymal transition (EMT) in SS cells.
      SHCBP1 knockdown could block the incidence of metastasis and EMT in SS cells.
      Furthermore, transforming growth factor-beta1 (TGF-beta1) induced SHCBP1
      expression in a time-dependent pattern and SHCBP1 knockdown inhibited TGF-beta1
      induced EMT. The activation of the TGF-beta1/Smad signaling pathway was involved
      in the oncogenic functions of SHCBP1 in SS. In addition, high expression of
      SHCBP1 in SS patients was associated with tumor progression and decreased
      survival as well as poor prognosis. CONCLUSIONS: Taken together, our results
      indicate that SHCBP1 may promote the metastasis of SS by inducing EMT through
      targeting TGF-beta1/Smad signaling pathway and can be a potential molecular
      target for SS therapy.

PMID- 29020989
TI  - Predictors of multidisciplinary rehabilitation outcomes in patients with chronic
      musculoskeletal pain: protocol for a systematic review and meta-analysis.
AB  - BACKGROUND: Chronic musculoskeletal pain is a major public health problem. Early
      prediction for optimal treatment results has received growing attention, but
      there is presently a lack of evidence regarding what information such proactive
      management should be based on. This study protocol, therefore, presents our
      planned systematic review and meta-analysis on important predictive factors for
      health and work-related outcomes following multidisciplinary rehabilitation (MDR)
      in patients with chronic musculoskeletal pain. METHODS: We aim to perform a
      synthesis of the available evidence together with a meta-analysis of published
      peer-reviewed original research that includes predictive factors preceding MDR.
      Included are prospective studies of adults with benign, chronic (> 3 months)
      musculoskeletal pain diagnoses who have taken part in MDR. In the studies,
      associations between personal and rehabilitation-based factors and the outcomes
      of interest are reported. Outcome domains are pain, physical functioning
      including health-related quality of life, and work ability with follow-ups of 6
      months or more. We will use a broad, explorative approach to any presented
      predictive factors (demographic, symptoms-related, physical, psychosocial, work
      related, and MDR-related) and these will be analyzed through (a) narrative
      synthesis for each outcome domain and (b) if sufficient studies are available, a
      quantitative synthesis in which variance-weighted pooled proportions will be
      computed using a random effects model for each outcome domain. The strength of
      the evidence will be evaluated using the Grading of Recommendations, Assessment,
      Development and Evaluation. DISCUSSION: The strength of this systematic review is
      that it aims for a meta-analysis of prospective cohort or randomized controlled
      studies by performing an extensive search of multiple databases, using an
      explorative study approach to predictive factors, rather than building on single
      predictor impact on the outcome or on predefined hypotheses. In this way, an
      overview of factors central to MDR outcome can be made and will help strengthen
      the evidence base and inform a wide readership including health care
      practitioners and policymakers. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42016025339.

PMID- 29020991
TI  - Building a bright, evidence-informed future: a conversation starter from the
      incoming editors.
AB  - Health Research and Policy Systems (HARPS) has gone from strength to strength
      since it was established in 2003. As new Editors-in-Chief, we look forward to a
      bright future for HARPS, and we would like to start a conversation with you,
      HARPS readers, authors, editors and others, about how HARPS can best support
      ongoing progress and debate on evidence-informed health research policy and
      systems, particularly in developing countries. As a starting point for
      discussion, we would like to highlight three areas that we are passionate about,
      namely supporting an integrated community of researchers and policy-makers;
      building a focus on how health research and policy systems can support
      achievement of the Sustainable Development Goals; and strengthening our
      commitment to communicating and disseminating the work published in HARPS. We
      invite you to contribute your thoughts, ideas and suggestions on the future of
      HARPS, as we work together towards an evidence-informed future.

PMID- 29020988
TI  - Haloperidol affects bones while clozapine alters metabolic parameters - sex
      specific effects in rats perinatally treated with phencyclidine.
AB  - BACKGROUND: The presentation of schizophrenia (SCH) symptoms differs between the
      sexes. Long-term treatment with antipsychotics is frequently associated with
      decreased bone mineral density, increased fracture risk and metabolic side
      effects. Perinatal phencyclidine (PCP) administration to rodents represents an
      animal model of SCH. The aim of this study was to assess the effects of chronic
      haloperidol and clozapine treatment on bone mass, body composition,
      corticosterone, IL-6 and TNF-alpha concentrations and metabolic parameters in
      male and female rats perinatally treated with PCP. METHODS: Six groups of male
      and six groups of female rats (n = 6-12 per group) were subcutaneously treated on
      2nd, 6th, 9th and 12th postnatal day (PN), with either PCP (10 mg/kg) or saline.
      At PN35, one NaCl and PCP group (NaCl-H and PCP-H) started receiving haloperidol
      (1 mg/kg/day) and one NaCl and PCP group (NaCl-C and PCP-C) started receiving
      clozapine (20 mg/kg/day) dissolved in drinking water. The remaining NaCl and PCP
      groups received water. Dual X-ray absorptiometry measurements were performed on
      PN60 and PN98. Animals were sacrificed on PN100. Femur was analysed by light
      microscopy. Concentrations of corticosterone, TNF-alpha and IL-6 were measured in
      serum samples using enzyme-linked immunosorbent assay (ELISA) commercially
      available kits. Glucose, cholesterol and triacylglycerol concentrations were
      measured in serum spectrophotometrically. RESULTS: Our results showed that
      perinatal PCP administration causes a significant decrease in bone mass and
      deterioration in bone quality in male and female rats. Haloperidol had
      deleterious, while clozapine had protective effect on bones. The effects of
      haloperidol on bones were more pronounced in male rats. It seems that the
      observed changes are not the consequence of the alterations of corticosterone, IL
      6 and TNF-alpha concentration since no change of these factors was observed.
      Clozapine induced increase of body weight and retroperitoneal fat in male rats
      regardless of perinatal treatment. Furthermore, clozapine treatment caused sex
      specific increase in pro-inflammatory cytokines. CONCLUSION: Taken together our
      findings confirm that antipsychotics have complex influence on bone and
      metabolism. Evaluation of potential markers for individual risk of antipsychotics
      induced adverse effects could be valuable for improvement of therapy of this life
      long lasting disease.

PMID- 29020990
TI  - A comparison of two different anthelmintic treatment regimens against natural
      gastrointestinal nematode infections on two Lithuanian sheep farms.
AB  - BACKGROUND: According to targeted treatment (TT), the whole flock is dewormed
      based on knowledge of the risk, or parameters that quantify the mean level of
      infection, whereas according to targeted selective treatment (TST), only
      individual animals within the grazing group are treated, based on
      parasitological, production and/or morbidity parameters. The aim of this study
      was to compare two different treatment protocols on sheep farms in Lithuania. The
      study was conducted from 15 April to 31 October 2014 on three sheep farms. On the
      TT (the whole flock) and T(S)T (with FECs >= 300, respectively) farms all adult
      animals were treated orally with fenbendazole irrespective of EPG counts before
      the grazing season. The second treatment was applied with injectable ivermectin
      on both farms. However, on the TT farm all sheep were also treated on 2nd August
      regardless of their EPG counts, while on the T(S)T farm only those animals with
      an EPG >= 300 were treated on 1 July using a threshold of >= 300 EPG. No
      treatments were administered on the control farm (n = 1) during the study.
      RESULTS: Spring treatment of ewes significantly reduced nematode faecal egg
      counts (FEC) both on the TT and T(S)T farms, with the benefit of lowering pasture
      contamination with infective L3 stage larvae at the start of grazing season,
      while it remained significantly higher on the control farm. The positive effect
      of the spring treatment of ewes was reflected by increased body weight gains
      (BWG) in lambs in the first half of the grazing season. Following the second
      treatment, the weight gains in lambs on the T(S)T farm were higher compared to
      lambs on the TT farm, while BWG in the control lambs started to decrease. The
      difference was also substantiated by the body condition scores (BCS) and dag
      scores (DS) of lambs, which were highest on the T(S)T farm compared with those on
      the control and TT farms. CONCLUSIONS: The results of this study show that both
      treatment strategies were useful in reducing clinical effects (BCS and DS) of
      gastrointestinal nematode parasitism and increasing the performance in lambs.
      Furthermore, on the T(S)T farm some of animals were left in refugia, helping to
      slow down the development of anthelmintic resistance (AR) in future.

PMID- 29020992
TI  - Facile aerobic construction of iron based ferromagnetic nanostructures by a novel
      microbial nanofactory isolated from tropical freshwater wetlands.
AB  - BACKGROUND: Iron based ferromagnetic nanoparticles (IONP) have found a wide range
      of application in microelectronics, chemotherapeutic cell targeting, and as
      contrast enhancers in MRI. As such, the design of well-defined monodisperse IONPs
      is crucial to ensure effectiveness in these applications. Although these
      nanostructures are currently manufactured using chemical and physical processes,
      these methods are not environmentally conducive and weigh heavily on energy and
      outlays. Certain microorganisms have the innate ability to reduce metallic ions
      in aqueous solution and generate nano-sized IONP's with narrow size distribution.
      Harnessing this potential is a way forward in constructing microbial
      nanofactories, capable of churning out high yields of well-defined IONP's with
      physico-chemical characteristics on par with the synthetically produced ones.
      RESULTS: In this work, we report the molecular characterization of an
      actinomycetes, isolated from tropical freshwater wetlands sediments, that
      demonstrated rapid aerobic extracellular reduction of ferric ions to generate
      iron based nanoparticles. Characterization of these nanoparticles was carried out
      using Field Emission Scanning Electron Microscope with energy dispersive X-ray
      spectroscopy (FESEM-EDX), Field Emission Transmission Electron Microscope
      (FETEM), Ultraviolet-Visible (UV-Vis) Spectrophotometer, dynamic light scattering
      (DLS) and Fourier transform infrared spectroscopy (FTIR). This process was
      carried out at room temperature and humidity and under aerobic conditions and
      could be developed as an environmental friendly, cost effective bioprocess for
      the production of IONP's. CONCLUSION: While it is undeniable that iron reducing
      microorganisms confer a largely untapped resource as potent nanofactories, these
      bioprocesses are largely anaerobic and hampered by the low reaction rates, highly
      stringent microbial cultural conditions and polydispersed nanostructures. In this
      work, the novel isolate demonstrated rapid, aerobic reduction of ferric ions in
      its extracellular matrix, resulting in IONPs of relatively narrow size
      distribution which are easily extracted and purified without the need for
      convoluted procedures. It is therefore hoped that this isolate could be
      potentially developed as an effective nanofactory in the future.

PMID- 29020993
TI  - Assessment of a Business-to-Consumer (B2C) model for Telemonitoring patients with
      Chronic Heart Failure (CHF).
AB  - BACKGROUND: The purpose of this study is to assess the Business-to-Consumer (B2C)
      model for telemonitoring patients with Chronic Heart Failure (CHF) by analysing
      the value it creates, both for organizations or ventures that provide
      telemonitoring services based on it, and for society. METHODS: The business model
      assessment was based on the following categories: caveats, venture type, six
      factor alignment, strategic market assessment, financial viability, valuation
      analysis, sustainability, societal impact, and technology assessment. The venture
      valuation was performed for three jurisdictions (countries) - Singapore, the
      Netherlands and the United States - in order to show the opportunities in a
      small, medium-sized, and large country (i.e. population). RESULTS: The business
      model assessment revealed that B2C telemonitoring is viable and profitable in the
      Innovating in Healthcare Framework. Analysis of the ecosystem revealed an average
      to-excellent fit with the six factors. The structure and financing fit was
      average, public policy and technology alignment was good, while consumer
      alignment and accountability fit was deemed excellent. The financial prognosis
      revealed that the venture is viable and profitable in Singapore and the
      Netherlands but not in the United States due to relatively high salary inputs.
      CONCLUSIONS: The B2C model in telemonitoring CHF potentially creates value for
      patients, shareholders of the service provider, and society. However, the
      validity of the results could be improved, for instance by using a peer-reviewed
      framework, a systematic literature search, case-based cost/efficiency inputs, and
      varied scenario inputs.

PMID- 29020994
TI  - Willingness to participate in pragmatic dialysis trials: the importance of
      physician decisional autonomy and consent approach.
AB  - BACKGROUND: Pragmatic clinical trials embedded in routine delivery of clinical
      care can lead to improvements in quality of care, but often have design features
      that raise ethical concerns. METHODS: We performed a discrete choice experiment
      and used conjoint analysis to assess how specific attributes of pragmatic
      dialysis trials influenced patients' and physicians' willingness to have their
      dialysis facility participate in a hypothetical trial of hypertension management.
      Electronic survey data were collected from 200 patients enrolled from 11
      outpatient hemodialysis units and from 203 nephrologists. The three attributes
      studied were physicians' treatment autonomy, participants' research burden, and
      the approach to consent. The influence of each attribute was quantified using
      mixed-effects logistic regression. RESULTS: Similar proportions of patients were
      willing to have their facilities participate in a trial with high vs. low
      physician autonomy (77% vs. 79%; p = 0.13) and research burden (76% vs. 80%; p =
      0.06). Opt-in, opt-out, and notification-only consent approaches were acceptable
      to most patients (84%, 82%, and 81%, respectively), but compared to each of these
      consent approaches, fewer patients (66%) were willing to have their facility
      participate in a trial that used no notification (p < 0.001 for each 2-way
      comparison). Among the physicians, similar proportions were willing to
      participate in trials with high and low physician autonomy (61% and 61%,
      respectively, p = 0.96) or with low and high burden (60 and 61%, respectively, p
      = 0.79). However, as for the patients, the consent approach influenced trial
      acceptability with 77%, 69%, and 62% willing to participate using opt-in, opt
      out, and notification-only, respectively, compared to no notification (36%) (p <
      0.001 for each 2-way comparison). CONCLUSIONS: Curtailing physician's treatment
      autonomy and increasing the burden associated with participation did not
      influence patients' or physicians' willingness to participate in the hypothetical
      research, suggesting that pragmatic dialysis trials are generally acceptable to
      patients and physicians. Both patients and physicians preferred consent
      approaches that include at least some level of patient notification, but the
      majority of patients were still willing to participate in trials that did not
      notify patients of the research.

PMID- 29020995
TI  - Sedation with propofol during ERCP: is the combination with esketamine more
      effective and safer than with alfentanil? Study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a
      gastrointestinal procedure that requires a relatively motionless patient during
      the intervention. Deep sedation by intravenous propofol combined with an opioid
      has recently become the preferred sedation technique. However, when high doses of
      propofol are used, side effects, namely respiratory depression, may occur.
      Esketamine has hypnotic, analgesic, and sympathomimetic effects. Our assumption
      is that a combination of propofol with esketamine reduces the dosage of
      individual drugs, thereby minimizing sedation side effects while keeping the same
      satisfaction level of patients and endoscopists. METHODS/DESIGN: The study will
      be performed as a randomized controlled multicenter trial. Patients undergoing
      ERCP, >= 18 years old, with American Society of Anesthesiologists (ASA)
      classification I-III will be randomized after written informed consent to group K
      (propofol/esketamine) or to group A (propofol/alfentanil). The primary outcome,
      reflecting effectiveness of sedation, is the total dose of propofol. Secondary
      outcome parameters are patients' and endoscopists' satisfaction with the
      procedure and the number of sedation-related pulmonary and cardiovascular events.
      Data on sedation-related events are collected by recording of oxygen saturation
      (SpO2), respiratory rate (RR), end-tidal CO2 (etCO2), heart rate (HR),
      arrhythmias (electrocardiogram (ECG)), and non-invasive blood pressure (NIBP)
      measurements. Satisfaction parameters are collected by means of questionnaires
      before and after the procedure and on the following day. DISCUSSION: Esketamine
      is known for its effective anesthetic and analgesic effects maintaining
      spontaneous breathing and airway reflexes. Due to an increase in sympathetic
      tone, hypotension and cardiac depression is less common. Unfortunately esketamine
      is also known for its psychotomimetic effects. We aim to demonstrate that the
      combination of esketamine with propofol for sedation in patients subjected to
      ERCP interventions is nevertheless superior to a combination of propofol with an
      opioid. TRIAL REGISTRATION: Nederland's Trial Register, NTR5486 . Registered on
      17 September 2015.

PMID- 29020996
TI  - Quality of life profile of general Vietnamese population using EQ-5D-5L.
AB  - BACKGROUND: Health-related quality of life (HRQOL) is a vital benchmark to assess
      the effects of health interventions and policies. Measuring HRQOL of the general
      population is essential to establish a reference for health outcomes evaluations.
      However, evidence on HRQOL of general populations in low and middle income
      countries is very limited. This study aimed to measure HRQOL of the Vietnamese
      population by using the EuroQol-5 dimensions-5 levels (EQ-5D-5L) instrument and
      determine its associated factors. METHODS: A cross-sectional study was performed
      in Hanoi with 1571 residences in Hanoi, the capital city of Vietnam. EQ-5D-5L and
      EQ- visual analogue scale (EQ-VAS) were used to assess HRQOL. Potential
      covariates included socio-demographic characteristics, having acute symptoms in
      the last four weeks, chronic diseases in the last three months, having multiple
      health issues, and health service utilisation in the last twelve months. A
      generalized linear model was employed to identify the association between HRQOL
      and covariates. RESULTS: Overall, the mean EQ-5D utility index was 0.91 (SD =
      0.15), and the mean EQ-VAS score was 87.4 (SD = 14.3). The highest proportion of
      respondents reporting any problems was in Usual activities (24.3%), followed by
      Anxiety/Depression (15.2%) and Pain/Discomfort (10.0%), while the lowest
      percentage was in Self-care (2.5%). Lower HRQOL composite scores were related to
      unemployment, lower income, higher education, living in urban areas, having
      chronic diseases, having multiple health issues and using health service. For any
      health problem self-reported by respondents, the health utility reduced by 0.02
      (respiratory diseases) to 0.15 (musculoskeletal diseases). CONCLUSIONS: Health
      utility of the general population and reductions for self-reported health
      problems in this study are useful for future population health evaluations and
      comparisons. It also informs the development of interventions to reduce health
      problems of the general population.

PMID- 29020997
TI  - Anterior cutaneous nerve entrapment syndrome with pain present only during
      Carnett's sign testing: a case report.
AB  - BACKGROUND: The identification of anterior cutaneous nerve entrapment syndrome is
      often challenging, due to no widely accepted standard guidelines regarding
      laboratory and imaging tests for the diagnosis of ACNES. CASE PRESENTATION: A 77
      year-old Japanese man presented with mild lower abdominal pain that had been
      present for the past 3 years. Physical examination revealed no abdominal pain
      during palpation, with normal laboratory and imaging testing; therefore,
      conservative therapy was initiated. However, the abdominal pain continued. Re
      examination 16 days later revealed three tender points in accordance with
      intercostal nerves Th10, Th11, and Th12, with the pain occurring only during
      Carnett's sign testing. A cutaneous injection of 1% lidocaine was administered,
      and the abdominal pain was resolved about 30 min later. Based on these results,
      anterior cutaneous nerve entrapment syndrome was diagnosed. CONCLUSIONS: It is
      sometimes hard to diagnose anterior cutaneous nerve entrapment syndrome without
      testing for Carnett's sign. If patients present with chronic abdominal pain,
      clinicians should test for Carnett's sign even if no pain is elicited during
      regular abdominal palpation.

PMID- 29021001
TI  - Correction to: More than 2500 years of oil exposure shape sediment microbiomes
      with the potential for syntrophic degradation of hydrocarbons linked to
      methanogenesis.

PMID- 29020998
TI  - Proteomic profiling of breast cancer metabolism identifies SHMT2 and ASCT2 as
      prognostic factors.
AB  - BACKGROUND: Breast cancer tumors are known to be highly heterogeneous and
      differences in their metabolic phenotypes, especially at protein level, are less
      well-understood. Profiling of metabolism-related proteins harbors the potential
      to establish new patient stratification regimes and biomarkers promoting
      individualized therapy. In our study, we aimed to examine the relationship
      between metabolism-associated protein expression profiles and clinicopathological
      characteristics in a large cohort of breast cancer patients. METHODS: Breast
      cancer specimens from 801 consecutive patients, diagnosed between 2009 and 2011,
      were investigated using reverse phase protein arrays (RPPA). Patients were
      treated in accordance with national guidelines in five certified German breast
      centers. To obtain quantitative expression data, 37 antibodies detecting proteins
      relevant to cancer metabolism, were applied. Hierarchical cluster analysis and
      individual target characterization were performed. Clustering results and
      individual protein expression patterns were associated with clinical data. The
      Kaplan-Meier method was used to estimate survival functions. Univariate and
      multivariate Cox regression models were applied to assess the impact of protein
      expression and other clinicopathological features on survival. RESULTS: We
      identified three metabolic clusters of breast cancer, which do not reflect the
      receptor-defined subtypes, but are significantly correlated with overall survival
      (OS, p <= 0.03) and recurrence-free survival (RFS, p <= 0.01). Furthermore,
      univariate and multivariate analysis of individual protein expression profiles
      demonstrated the central role of serine hydroxymethyltransferase 2 (SHMT2) and
      amino acid transporter ASCT2 (SLC1A5) as independent prognostic factors in breast
      cancer patients. High SHMT2 protein expression was significantly correlated with
      poor OS (hazard ratio (HR) = 1.53, 95% confidence interval (CI) = 1.10-2.12, p <=
      0.01) and RFS (HR = 1.54, 95% CI = 1.16-2.04, p <= 0.01). High protein expression
      of ASCT2 was significantly correlated with poor RFS (HR = 1.31, 95% CI = 1.01
      1.71, p <= 0.05). CONCLUSIONS: Our data confirm the heterogeneity of breast
      tumors at a functional proteomic level and dissects the relationship between
      metabolism-related proteins, pathological features and patient survival. These
      observations highlight the importance of SHMT2 and ASCT2 as valuable individual
      prognostic markers and potential targets for personalized breast cancer therapy.
      TRIAL REGISTRATION: ClinicalTrials.gov, NCT01592825 . Registered on 3 May 2012.

PMID- 29020999
TI  - Beneficial effects of Heqi san on rat model of polycystic ovary syndrome through
      the PI3K/AKT pathway.
AB  - BACKGROUND: Heqi San, a traditional Chinese medicine (TCM) has been reported to
      regulate hormone levels in patients with metabolic disease, suggesting a
      potential clinical application. In the current study, we aimed to elucidate the
      effect of Heqi San on rat model of polycystic ovary syndrome (PCOS). METHOD: PCOS
      model was established in female SD rats. Rats were randomly divided into four
      groups: the control, untreated PCOS model, Heqi San treated PCOS model (8.1 g/kg)
      and metformin (MET) treated PCOS model (135 mg/kg) groups. All animals were
      subcutaneously injected with 6 mg/100 g dehydroepiandrosterone (DHEA) in the neck
      once a day for 20 consecutive days. The serum hormone levels were measured by
      ELISA. The ovarian tissues were stained with hematoxylin and eosin (HE) to
      undergo pathological examination. The expression levels of GLTU4 and PTEN mRNA
      were examined by real time PCR. The crucial proteins in the PI3K/APT pathway were
      analyzed by western blotting. Then, the functions of the target genes were
      analyzed using bioinformatics approaches. RESULTS: We found that Heqi San was
      able to recover the serum hormone levels and improve insulin resistance in PCOS
      rat model. A morphological lesion of the ovary was also restored with the Heqi
      San treatment. More importantly, we discovered a correlation between the PI3K/AKT
      signaling pathway and the beneficial effects of Heqi San, demonstrating that its
      application could alter the expression levels of p-ERK, p-AKT, p-GSK3beta, IRS-1,
      PTEN and GLTU4, all key factors in the PI3K/APT pathway. Through a
      bioinformatical analysis, we predicted the related gene function and pathway of
      the pathological mechanism of PCOS and found miRNAs that are likely to be
      critical in PCOS occurrence, including rno-miR-144-3p, rno-miR-30c-2-3p, rno-miR
      486, rno-miR-3586-3p and rno-miR-146b-5p. CONCLUSION: The beneficial effects of
      Heqi on PCOS, including alter serum hormone levels, recover ovary morphological
      lesions and improve insulin resistance, which is mediated through the PI3K/AKT
      pathway. The potential role of miRNA-144-3p in PCOS pathogenesis.

PMID- 29021000
TI  - The Swedish study of Irrigation-fluid temperature in the evacuation of Chronic
      subdural hematoma (SIC!): study protocol for a multicenter randomized controlled
      trial.
AB  - BACKGROUND: Chronic subdural hematoma (cSDH) is one of the most common conditions
      encountered in neurosurgical practice. Recurrence, observed in 5-30% of patients,
      is a major clinical problem. The temperature of the irrigation fluid used during
      evacuation of the hematoma might theoretically influence recurrence rates since
      irrigation fluid at body temperature (37 oC) may beneficially influence
      coagulation and cSDH solubility when compared to irrigation fluid at room
      temperature. Should no difference in recurrence rates be observed when comparing
      irrigation-fluid temperatures, there is no need for warmed fluids during surgery.
      Our main aim is to investigate the effect of irrigation-fluid temperature on
      recurrence rates and clinical outcomes after cSDH evacuation using a multicenter
      randomized controlled trial design. METHODS: The study will be conducted in three
      neurosurgical departments with population-based catchment areas using a similar
      surgical strategy. In total, 600 patients fulfilling the inclusion criteria will
      randomly be assigned to either intraoperative irrigation with fluid at body
      temperature or room temperature. The power calculation is based on a
      retrospective study performed at our department showing a recurrence rate of 5%
      versus 12% when comparing irrigation fluid at body temperature versus fluid at
      room temperature (unpublished data). The primary endpoint is recurrence rate of
      cSDH analyzed at 6 months post treatment. Secondary endpoints are mortality rate,
      complications and health-related quality of life. DISCUSSION: Irrigation-fluid
      temperature might influence recurrence rates in the evacuation of chronic
      subdural hematomas. We present a study protocol for a multicenter randomized
      controlled trial investigating our hypothesis that irrigation fluid at body
      temperature is superior to room temperature in reducing recurrence rates
      following evacuation of cSDH. TRIALS REGISTRATION: ClinicalTrials.gov, ID:
      NCT02757235 . Registered on 2 May 2016.

PMID- 29021003
TI  - Seasonality in Multiple Maternities.
AB  - In the 19th century, a series of international statistical congresses introduced
      common rules for the national demographic registers. This activity contributed to
      the genesis of statistical research. During the history of twin research,
      Hellin's law has played a central role because it is an approximately correct
      association between the rates of multiple maternities. However, it has been
      mathematically proven that Hellin's law cannot hold exactly. The majority of all
      studies of Hellin's law are based on empirical rates of multiple maternities.
      Such studies can never confirm the law, but only identify errors too large to be
      characterized as random. It is of particular interest to examine why the rates of
      higher multiple maternities are sometimes too high or too low when Hellin's law
      is used as a benchmark. However, divergences from the law are often difficult to
      explain and/or eliminate. Different improvements to the law have been proposed.
      In this article, we study the seasonality of multiple maternities. We apply
      Hellin's law to compare the seasonality of twin and triplet rates.

PMID- 29021005
TI  - Trends in depression prevalence in the USA from 2005 to 2015: widening
      disparities in vulnerable groups.
AB  - BACKGROUND: Major depression is associated with significant disability,
      morbidity, and mortality. The current study estimated trends in the prevalence of
      major depression in the US population from 2005 to 2015 overall and by
      demographic subgroups. METHODS: Data were drawn from the National Survey on Drug
      Use and Health (NSDUH), an annual cross-sectional study of US persons ages 12 and
      over (total analytic sample N = 607 520). Past-year depression prevalence was
      examined annually among respondents from 2005 to 2015. Time trends in depression
      prevalence stratified by survey year were tested using logistic regression. Data
      were re-analyzed stratified by age, gender, race/ethnicity, income, and
      education. RESULTS: Depression prevalence increased significantly in the USA from
      2005 to 2015, before and after controlling for demographics. Increases in
      depression were significant for the youngest and oldest age groups, men, and
      women, Non-Hispanic White persons, the lowest income group, and the highest
      education and income groups. A significant year * demographic interaction was
      found for age. The rate of increase in depression was significantly more rapid
      among youth relative to all older age groups. CONCLUSIONS: The prevalence of
      depression increased significantly in the USA from 2005 to 2015. The rate of
      increase in depression among youth was significantly more rapid relative to older
      groups. Further research into understanding the macro level, micro level, and
      individual factors that are contributing to the increase in depression, including
      factors specific to demographic subgroups, would help to direct public health
      prevention and intervention efforts.

PMID- 29021006
TI  - Determination of Total Biotin by Liquid Chromatography Coupled with
      Immunoaffinity Column Cleanup Extraction: Multilaboratory Testing, Final Action
      2016.02.
AB  - Single- and multilaboratory testing data have provided systematic scientific
      evidence that a simple, selective, accurate, and precise method can be used as a
      potential candidate reference method for dispute resolution in determining total
      biotin in all forms of infant, adult, and/or pediatric formula. Using LC coupled
      with immunoaffinity column cleanup extraction, the method fully meets the
      intended purpose and applicability statement in AOAC Standard Method Performance
      Requirement 2014.005. The method was applied to a cross-section of infant formula
      and adult nutritional matrixes, and acceptable precision and accuracy were
      established. The analytical platform is inexpensive, and the method can be used
      in almost any laboratory worldwide with basic facilities. The immunoaffinity
      column cleanup extraction is the key step to successful analysis.

PMID- 29021004
TI  - Saduria entomon infected with Hysterothylacium aduncum found in situ in the
      stomach of cod (Gadus morhua) from the Baltic Sea.
AB  - The parasite fauna of cod (Gadus morhus) is well described, but the life cycles
      of Baltic cod parasites are known only in general terms. Invertebrates commonly
      found in the stomach of cod are recognized as intermediate hosts in the life
      cycles of nematodes or acanthocephalans. The aim of this study was to determine
      the source of infection of Baltic cod with parasites found in situ in
      invertebrates present in the cod stomach. Our results indicate that Saduria
      entomon is both a source of infection of Baltic cod with parasites and an
      intermediate host in the life cycle of Hysterothylacium aduncum in the Baltic
      Sea.

PMID- 29021007
TI  - The Senior Care Pharmacist's Role in Transitions of Care.

PMID- 29021002
TI  - Collagen triple helix repeat containing 1 (CTHRC1) activates Integrin beta3/FAK
      signaling and promotes metastasis in ovarian cancer.
AB  - BACKGROUND: Metastasis is the major cause of morbidity and mortality in patients
      with epithelial ovarian cancer (EOC), however the mechanisms that underline this
      process are poorly understood. Collagen triple helix repeat containing-1 (CTHRC1)
      is a 28-kDa secreted protein reported to be involved in vascular remodeling, bone
      formation and morphogenesis. This study aimed to investigate the role of CTHRC1
      in promoting the metastasis of EOC and to elucidate the underlying molecular
      mechanisms. METHODS: The biologic functions of CTHRC1 in metastasis were
      validated both in vivo and in vitro experiments. The phosphor-antibody microarray
      analysis and Co-immunoprecipitation were performed to detect and identify the
      integrin beta3/FAK signaling pathway that mediated the function of CTHRC1.
      Seventy two EOC samples were analyzed for association between CTHRC1/integrin
      beta3 expression and patient clinicopathological features. RESULTS: We
      demonstrated that CTHRC1 enhances the biological behavior of EOC including cell
      migration, invasion, as well as its adhesion capability to cell-extracellular
      matrix in vitro. Additionally, CTHRC1 promoted metastatic spread of EOC cells in
      an i.p. ovarian xenograft model and this phenotype was primarily ascribed to the
      activation of integrin/FAK signaling. Mechanistically, we determined that FAK
      were phosphorylated on Tyr397, and were activated by integrin beta3, which is
      important for the CTHRC1-mediated migratory and invasive ability of EOC cells in
      vitro and i.p. metastasis. In addition, we found that attenuated CTHRC1/integrin
      beta3 expression predicted a poor prognostic phenotype and advanced clinical
      stage of EOC. CONCLUSIONS: Our results suggest that CTHRC1, a newly identified
      regulator of i.p. metastasis through activation of integrin beta3/FAK signaling
      in EOC, may represent a potential therapeutic target for ovarian cancer.

PMID- 29021008
TI  - Medication Review and Transitions of Care: A Case Report of a Decade-Old
      Medication Error.
AB  - A 69-year-old Caucasian male with a 25-year history of paranoid schizophrenia was
      brought to the emergency department because of violence toward the staff in his
      nursing facility. He was diagnosed with a urinary tract infection and was
      admitted to the behavioral health unit for medication stabilization. History
      included a five-year state psychiatric hospital admission and nursing facility
      placement. Because of poor cognitive function, the patient was unable to
      corroborate medication history, so the pharmacy student on rotation performed an
      in-depth chart review. The review revealed a transcription error in 2003 deleting
      amantadine 100 mg twice daily and adding amiodarone 100 mg twice daily.
      Subsequent hospitalization resulted in another transcription error increasing the
      amiodarone to 200 mg twice daily. All electrocardiograms conducted were negative
      for atrial fibrillation. Once detected, the consulted cardiologist discontinued
      the amiodarone, and the primary care provider was notified via letter and
      discharge papers. An admission four months later revealed that the nursing
      facility restarted the amiodarone. Amiodarone was discontinued and the facility
      was again notified. This case reviews how a 10-year-old medication error went
      undetected in the electronic medical records through numerous medication
      reconciliations, but was uncovered when a single comprehensive medication review
      was conducted.

PMID- 29021009
TI  - Optimizing the Use of Discharge Medication Lists in Nursing Facilities.
AB  - OBJECTIVE: To highlight the need to optimize the use of discharge medication
      lists in nursing facilities. SETTING: In January 2014, the care transitions (CT)
      pharmacists at Frederick Memorial Hospital, Frederick, Maryland, began a pilot
      project in which they identified and followed high-risk patients transitioning
      from hospital to nursing facility and from nursing facility to home. PRACTICE
      DESCRIPTION: This pilot project served as a needs assessment to identify
      opportunities to improve patients' transition from nursing facility to home with
      the goal of reducing hospital readmissions. PRACTICE INNOVATION: One of the
      enormous opportunities that were immediately recognized was the nursing facility
      discharge medication list. MAIN OUTCOME MEASUREMENTS: The CT pharmacists found
      that patients had difficulty deciphering and understanding the medication lists.
      RESULTS: By reviewing the elements of existing medication lists, the CT
      pharmacists identified 11 components of a nursing facility discharge medication
      list that would increase patient safety and potentially reduce medication-related
      hospital readmissions. These elements include the capability of electronically
      generating a medication list that includes both brand and generic medication
      names with accurate indications in layperson terms. The ideal discharge
      medication list would also be patient-specific and remove irrelevant information
      and take into consideration patients' age, vision, and health literacy.
      CONCLUSION: With the upcoming implementation of the nursing facility value-based
      purchasing program, nursing facilities may soon receive incentives to improve
      their medication management systems at discharge.

PMID- 29021010
TI  - Exposure to Community Violence Among Low-Income African American Youth in
      Chicago: A Latent Class Analysis.
AB  - African American youth are exposed to some of the highest rates of exposure to
      community violence. However, few studies have explored factors related to
      exposures and various subtypes of exposures to community violence (i.e., no
      exposure, witnessing only and being a witness/victim). Among a matched sample of
      129 African American youth and their caregivers, no exposure to community
      violence was correlated with being heterosexual versus being a lesbian, gay,
      bisexual, and transgender (LGBT) person, having parents who owned their homes
      versus rented, and having higher authoritarian parenting attitudes. In addition,
      being a witness/victim of community violence was correlated with any youth
      substance use, lower levels of school bonding, having less future orientation,
      less parental home ownership, and an adverse family history. Practice and
      programmatic considerations are discussed based on these findings.

PMID- 29021012
TI  - The Role of Entitlement, Self-Control, and Risk Behaviors on Dating Violence
      Perpetration.
AB  - Dating violence continues to be pervasive among college students (Stappenbeck &
      Fromme, 2010). Given the paucity of research investigating the various pathways
      through which risk factors are linked to dating violence among different college
      campuses, we use multiple group path analysis to examine the role of child abuse,
      self-control, entitlement, and risky behaviors on dating violence perpetration
      among college students from one Southeastern and one Midwestern university. There
      were 1,482 college students (51% female) enrolled in undergraduate courses at 2
      large public universities who completed paper and pencil surveys. Dating violence
      perpetration was directly associated with gender, child physical abuse, and
      sexual and drug risk behaviors and indirectly associated with college Greek
      letter fraternity affiliation, self-control, and entitlement. Moreover,
      significant differences in the pathways to dating violence were found between the
      Southeast and Midwest campuses.

PMID- 29021011
TI  - Intimate Partner Violence Victimization and Cognitive Function in a Mixed-Sex
      Epidemiological Sample of Urban Adults.
AB  - Intimate partner violence (IPV) victimization is associated with a wide range of
      mental and physical health problems, but little is known about the effect of IPV
      on cognitive decline. Previous research suggests an association between IPV
      victimization and cognitive dysfunction, but the few studies that have examined
      this phenomenon were cross-sectional in design and focused only on female victims
      of IPV. This study examined cognitive function over time among a diverse
      population of both male and female victims of IPV. Regression analyses indicated
      increased completion time on Trail Making Test (TMT) A for both male and female
      victims of IPV living below poverty as well as for female victims of IPV without
      previously depressive symptomatology. Results also indicated increased completion
      time on TMT B for male victims of IPV. Our findings support an association
      between IPV victimization and increased cognitive decline that is moderated by
      poverty status and previous depressive symptomatology.

PMID- 29021013
TI  - A Short Measure of Social Reactions to Sexual Assault: The Social Reactions
      Questionnaire-Shortened.
AB  - Social reactions to disclosures of sexual assault have significant effects on
      women's postassault recovery. However, being the most widely used measure of
      these reactions, the 48-item Social Reactions Questionnaire (SRQ; Ullman, 2000)
      is too long for some research and evaluation efforts. Thus, we developed a 16
      item short version, the Social Reactions Questionnaire-Shortened (SRQ-S). Three
      preexisting college and community samples of women survivors (N = 1,012; 1,084;
      and 344) were used to determine which SRQ items were most related to
      psychological symptoms and could form reliable subscales. The brief version was
      then administered in a college and community sample of 447 women survivors.
      Confirmatory factor analyses (CFAs) and supporting psychometrics showed the SRQ-S
      reliably measures three general scales of the SRQ (Turning Against, Unsupportive
      Acknowledgment, Positive Reactions) as well as eight 2-item subscales (e.g.,
      Blame). The SRQ-S provides researchers and interventionists with a brief
      alternative measure to the original SRQ.

PMID- 29021014
TI  - What Is the Optimal Dose and Schedule for Dasatinib in Chronic Myeloid Leukemia:
      Two Case Reports and Review of the Literature.
AB  - Efficacy and safety of dasatinib in chronic phase (CP) chronic myelogenous
      leukemia (CML) patients has been well established. Initially approved dose and
      schedule of 70 mg twice daily has been changed to 100 mg once daily after
      demonstration of the same efficacy with less toxicity. Some patients require
      significant dose reductions to enable continued treatment with dasatinib. Even at
      a dose of 80 mg once daily, several patients may require further dose reductions
      due to substantial toxicity while maintaining good control of their disease. We
      report two CP-CML patients achieving and maintaining major molecular responses
      while on very low doses of dasatinib, ultimately achieving undetectable levels of
      BCR-ABL fusion transcript in their peripheral blood. Observations of several CP
      CML cases responding remarkably well to dasatinib despite very low dose and
      frequent dose interruptions challenge our current understanding and the accuracy
      of the data regarding the optimum dose and schedule of this drug. In selected
      intolerant patients, low-dose dasatinib therapy may be a safe and effective
      alternative treatment option before a treatment discontinuation or change
      considered.

PMID- 29021015
TI  - Knockdown of Legumain Suppresses Cervical Cancer Cell Migration and Invasion.
AB  - Cervical cancer is the second leading type of cancer in women living in less
      developed countries. The pathological and molecular mechanisms of cervical cancer
      are not comprehensively known. Though legumain has been found to be highly
      expressed in various types of solid tumors, its expression and biological
      function in cervical cancer remain unknown. In this study, we aimed to
      investigate legumain expression and functions in cervical cancer. We found that
      legumain was highly expressed in cervical cancer cells. When knocked down,
      legumain expression in HeLa and SiHa cells significantly reduced its migration
      and invasion abilities compared with control cells. Furthermore, legumain
      silencing suppressed the activation of matrix metalloproteases (MMP2 and MMP3) in
      cervical cancer cells. This study indicates that legumain might play an important
      role in cervical cancer cell migration and invasion. Legumain might be a
      potential therapeutic target for cervical cancer therapy.

PMID- 29021016
TI  - Tumor-Suppressor Gene NBPF1 Inhibits Invasion and PI3K/mTOR Signaling in Cervical
      Cancer Cells.
AB  - The purpose of this study was to assess the effects of NBPF1 expression on
      cervical cancer cell invasion and apoptosis and to illustrate its potential
      mechanism. Human cervical cancer HeLa cells were transfected with the constructed
      siNBPF1 or pcDNA3.1-NBPF1 vectors. Effects of NBPF1 expression on cell invasion
      ability and cell apoptosis were analyzed using the Matrigel method and an Annexin
      V-FITC cell apoptosis kit, respectively. In addition, cell apoptosis-related
      proteins involved with the PI3K/mTOR signaling pathway were analyzed using
      Western blot. Remediation experiments were conducted to verify the effects of
      NBPF1 expression on cell invasion and apoptosis. Compared to the control, mRNA
      and protein expressions of NBPF1 were significantly decreased when cells were
      transfected with siNBPF1 (p < 0.05), which was contrary to the results of cells
      transfected with pcDNA3.1-NBPF1. Overexpression of NBPF1 significantly suppressed
      HeLa cell invasion but promoted cell apoptosis (p < 0.05). Overexpression of
      NBPF1 performed a significant inhibitory role on PI3K/mTOR signal pathway
      expression, while NBPF1 was silenced, showing contrary results. Our data
      suggested that NBPF1 overexpression may be a suppressor for cervical cancer via
      affecting cell invasion and apoptosis through regulating PI3K/mTOR signaling
      pathway. NBPF1 may be a potential therapeutic target for cervical cancer
      treatment.

PMID- 29021017
TI  - Inhibition of NF-kappaB Activity Enhances Sensitivity to Anticancer Drugs in
      Cholangiocarcinoma Cells.
AB  - Cholangiocarcinoma (CCA) is a dismal cancer. At present, there is no effective
      chemotherapeutic regimen for CCA. This may be due to the marked resistance of CCA
      to chemotherapy drugs, for which a mechanism remains unknown. Nuclear factor
      kappaB (NF-kappaB) is constitutively activated in a variety of cancer cells,
      including CCA. It has been shown to play roles in growth, metastasis, and
      chemoresistance of cancer. In the present study, we examined whether NF-kappaB is
      involved in the chemoresistance of CCA and whether dehydroxymethylepoxyquinomicin
      (DHMEQ), an effective NF-kappaB inhibitor, can overcome the drug resistance of
      CCA. Two CCA cell lines, KKU-M213 and KKU-M214, were treated with DHMEQ and/or
      chemotherapeutic drugs. Cell viability, apoptosis, and the expressions of the ATP
      binding cassette (ABC) transporters were compared. The combination of
      chemotherapy drugs, 5-fluorouracil, cisplatin, and doxorubicin, with DHMEQ
      significantly enhanced the cytotoxicity of all chemotherapeutic drugs compared to
      DHMEQ or drug alone. Furthermore, the mRNA level of ABCB1, a multidrug-resistant
      protein, was significantly decreased in the 5-fluorouracil combined with DHMEQ
      treated cells. These findings suggest that the inhibition of NF-kappaB by DHMEQ
      enhanced the chemoresponsiveness of CCA cells, possibly by reducing the
      expression of ABC transporter. Inhibition of NF-kappaB may be a potential
      chemodrug-sensitizing strategy for chemoresistant cancer such as CCA.

PMID- 29021018
TI  - Curcumin Enhances the Effects of 5-Fluorouracil and Oxaliplatin in Inducing
      Gastric Cancer Cell Apoptosis Both In Vitro and In Vivo.
AB  - Despite the efficacy of fluoropyrimidines and oxaliplatin-based chemotherapy for
      patients, this treatment leads to significant patient inconvenience, toxicity,
      and cost. This study aims to validate a nontoxic agent, curcumin, to the current
      chemotherapeutic regimen. In in vitro experiments, curcumin induced apoptosis in
      gastric cancer cell line BGC-823. Synergistic antitumor effects of curcumin were
      observed in combination with 5-fluorouracil (5-FU) and oxaliplatin. These effects
      were accompanied by downregulation of the expression of Bcl-2 protein and mRNA
      and upregulation of the expression of Bax and caspase 3, 8, and 9. In addition,
      the in vivo study showed that the combination of curcumin and 5-FU/oxaliplatin
      exhibited potent growth inhibition of BGC-823 xenograft tumors. Furthermore,
      compared with the control group, no significant difference was observed in the
      body weight of curcumin-treated nude mice. In conclusion, curcumin may act
      synergistically with the chemotherapeutic regimen FOLFOX in gastric cancer in
      vitro and in vivo by inducing apoptosis via Bcl/Bax-caspase 8,9-caspase 3
      pathway.

PMID- 29021019
TI  - Enhancement of Chemosensitivity by Stathmin-1 Silencing in Gastric Cancer Cells
      In Situ and In Vivo.
AB  - Reports show that the stathmin gene may have a close relationship with tumor
      chemotherapeutic sensitivity. However, the effect of stathmin-1 on the
      chemosensitivity of gastric cancer to docetaxel has not been clearly determined.
      siRNA targeting stathmin-1 was introduced. The cell growth inhibition, expression
      of associated proteins, cell cycle, and apoptosis were evaluated by MTT, Western
      blot, and flow cytometric assays, respectively. The influence of silencing
      stathmin-1 was detected in situ and in vivo. SGC7901/docetaxel cells are the drug
      resistant cells. After silencing stathmin-1, the resistance index (RI) reduced to
      3.41, the expressions of STMN-1, MDR1, and ERCC1 were downregulated, but caspase
      3 was upregulated. Stathmin-1 siRNA could improve the chemosensitivity of gastric
      cancer cells to docetaxel, making the percentage of cells at the sub-G1 stage
      increase and promote apoptosis. The growth of transplantation tumor was
      significantly suppressed. Therefore, stathmin-1 might be a potential target for
      enhancing the chemosensitivity of gastric cancer.

PMID- 29021020
TI  - Overexpression of NDRG2 Increases Iodine Uptake and Inhibits Thyroid Carcinoma
      Cell Growth In Situ and In Vivo.
AB  - Medullary thyroid carcinoma (MTC) is an uncommon and highly aggressive tumor of
      the neuroendocrine system, which derives from the neuroendocrine C cells of the
      thyroid gland. Except for surgical resection, there are not very many effective
      systemic treatment options for MTC. N-Myc downstream-regulated gene 2 (NDRG2) had
      a significantly lower expression in MTC compared with normal thyroid tissue.
      However, the function of NDRG2 in MTC oncogenesis is largely unknown. In this
      study, we found that overexpression of NDRG2 inhibited the proliferation of TT
      cells (human medullary thyroid carcinoma cells) in vitro and suppressed the
      development of MTC in a nude mouse xenograft model. Further analysis revealed
      that NDRG2 arrested the cell cycle G0/G1 phase progression and induced TT cell
      apoptosis. Moreover, NDRG2 overexpression may mediate the antiproliferative
      effect by reducing cyclin D1 and cyclin E protein levels. We also found aberrant
      NDRG2-mitigated TT cell migration and invasion in vitro. Sodium/iodide symporter
      (NIS) mediates active I- transport into the thyroid follicular cells, and
      radionuclide treatment is a promising therapy for MTC. Our current data revealed
      that NDRG2 overexpression enhanced NIS level in TT cells and increased their
      iodine uptake in vitro. Furthermore, 99mTcO4- radionuclide imaging of the
      xenograft tumors indicated that NDRG2 could promote NIS-mediated radionuclide
      transport. In conclusion, the present study suggested that NDRG2 is a critical
      molecule in the regulation of MTC biological behavior and a potential promoter in
      radioactive iodine therapy.

PMID- 29021021
TI  - Inhibition of Lung Carcinoma A549 Cell Growth by Knockdown of Hexokinase 2 In
      Situ and In Vivo.
AB  - Hexokinase 2 (HK2) has been identified as an oncogene in some malignant diseases
      such as breast cancer and ovarian cancer. However, the role of HK2 in lung cancer
      remains unclear. In this study, we explored the functional role of HK2 in lung
      cancer cell proliferation and tumorigenesis and determine its expression profile
      in lung cancer. HK2 expression was increased in primary lung cancer tissues of
      patients. Knocking down HK2 expression by small interfering RNA (siRNA) inhibited
      cell proliferation in lung cancer cells and nude mice. Thus, HK2 is required for
      sustained proliferation and survival of tumor cells in vitro and in vivo, and its
      aberrant expression may contribute to the pathogenesis of lung cancer. Thus, our
      study provided evidence that HK2 functions as a novel oncogene in lung cancer and
      may be a potential therapeutic target for lung cancer.

PMID- 29021022
TI  - Reduced PDCD4 Expression Promotes Cell Growth Through PI3K/Akt Signaling in Non
      Small Cell Lung Cancer.
AB  - It is largely recognized that PDCD4 is frequently lost in tumors of various
      origins, including lung cancer, and its loss contributes to tumor progression.
      However, its role and molecular mechanism remain largely unexplored in non-small
      cell lung cancer (NSCLC). In this study, downregulated PDCD4 mRNA expression was
      found in NSCLC tissues compared to their corresponding paracarcinoma tissues and
      distal paracarcinoma tissues. Induced expression of PDCD4 inhibited cell growth
      and proliferation and cell cycle transition in vitro. Conversely, knocking down
      PDCD4 expression promoted cell growth and proliferation. Mechanistically, PDCD4
      inactivated PI3K/Akt signaling and its downstream cell cycle factors CCND1 and
      CDK4 to regulate cell growth in NSCLC. Additionally, PI3K-specific inhibitor
      Ly294002 suppressed the expression of pPI3K (Tyr458), pAkt (Ser473), CCND1, and
      CDK4 in PC9-shPDCD4 and A549-shPDCD4 cells. Furthermore, Akt-specific inhibitor
      MK2206 inhibited the expression of pAkt (Ser473), CCND1, and CDK4 in PC9-shPDCD4
      and A549-shPDCD4 cells. Taken together, our study provides evidence that PDCD4
      inhibits cell growth through PI3K/Akt signaling in NSCLC and may be a potential
      therapeutic target for NSCLC.

PMID- 29021023
TI  - Knockdown of microRNA-29a Changes the Expression of Heat Shock Proteins in Breast
      Carcinoma MCF-7 Cells.
AB  - Breast cancer is the most commonly occurring cancer among women. MicroRNAs as
      noncoding small RNA molecules play pivotal roles in cancer-related biological
      processes. Increased levels of microRNA-29a in the serum of breast cancer
      patients have been reported. Since heat shock proteins (HSPs) play important
      roles in cell events, the quantitative fluctuations in their cellular levels
      could be deemed as key indicators of how the exerted treatment alters cell
      behavior. In this regard, using an antisense small RNA, we attempted to
      investigate the effects of miR-29a knockdown on the expression of HSPs genes in
      the MCF-7 breast cancer cell line. MCF-7 cells were cultured in high-glucose
      Dulbecco's modified Eagle's medium with 10% FBS. Studied cells were subdivided
      into five groups: treated with scramble, anti-miR-29a, anti-miR-29a + Taxol,
      Taxol, and control. Taxol was added 24 h post-anti-miR transfection and RNA
      extraction, and cDNA synthesis was done 48 h later. The changes in expression of
      HSP27, HSP40, HSP60, HSP70, and HSP90 were evaluated by real-time PCR. Our
      results revealed that inhibitors of microRNA-29a promote apoptosis through
      upregulation of HSP60 level and downregulation of HSP27, HSP40, HSP70, and HSP90
      levels and could be contemplated as a compelling alternative for Taxol employment
      with similar effects and/or to sensitize cancer cells to chemotherapy with fewer
      side effects.

PMID- 29021024
TI  - Apoptotic Melanoma B16-F1 Cells Induced by Lidamycin Could Initiate the Antitumor
      Immune Response in BABL/c Mice.
AB  - In the process of tumor cell apoptosis induced by specific regents, calreticulin
      (CRT) was transferred from endoplasmic reticulum (ER) onto the cell membrane.
      These tumor cells, when used as the cellular vaccine to immunize experimental
      animals, could initiate effective antitumor immunoresponse against homologous
      tumor cells. This is referred to as immunogenic cell death. Lidamycin (LDM) is an
      enediyne antibiotic, which has extremely potent cytotoxicity to cancer cells. In
      this study, the mouse melanoma B16-F1 cancer cells were used to investigate the
      ability of LDM in promoting immunogenic cell death. Our data showed that LDM
      could induce apoptosis of B16-F1 cancer cells, accompanied by CRT translocation
      onto the cell membrane. These LDM-treated B16-F1 cells could be recognized and
      phagocytosed more efficiently by macrophage and dendritic cells. When the LDM
      treated apoptotic B16-F1 cells were used as a whole-cell tumor vaccine to immune
      mice, the mice obtained resistance against rechallenged B16-F1 living cells. At
      the same time, the specific antitumor immune response was observed in these
      vaccinated mice. The splenocytes from the mice vaccinated with LDM-treated B16-F1
      cells showed significantly enhanced NK lymphocyte activities and also faster
      growth rate and increased secretion of IFN-gamma when encountering the cellular
      antigens from B16-F1 cells. All these results suggested that LDM could promote
      immunogenic cell death in B16-F1 cells, and these LDM-treated B16-F1 cells could
      be used as a sort of cell vaccine to initiate effective antitumor immunoresponse
      in mice.

PMID- 29021026
TI  - Editorial.

PMID- 29021025
TI  - ERRATUM.
AB  - Histone deacetylase (HDAC) inhibitors have been shown to enhance the effects of 5
      fluorouracil (5-FU) against various cancer cells; however, no report has shown
      that an HDAC inhibitor may enhance the effects of 5-FU with radiation. Therefore,
      we investigated whether the novel HDAC inhibitor OBP-801/YM753 could enhance the
      effects of 5-FU with radiation on esophageal squamous carcinoma KYSE170 cells.
      The inhibition of the cell growth was significantly stronger with the combination
      of OBP-801/YM753 with 5-FU than with the 5-FU treatment only. Furthermore,
      inhibition of the colony formation was the most effective with the combined
      treatment of OBP-801/YM753, 5-FU, and radiation. Western blot analysis showed
      that OBP-801/YM753 suppressed the expression of thymidylate synthase induced by 5
      FU. Therefore, this three-combined therapy is promising for patients with
      esophageal squamous carcinoma.

PMID- 29021027
TI  - Chapter 1: Sinonasal anatomy and function.
AB  - An understanding of paranasal sinus anatomy based on important fixed landmarks
      rather than variable anatomy is critical to ensure safe and complete surgery. The
      concept of the paranasal surgical box defines the anatomic limits of dissection.
      The boundaries of the surgical box include the middle turbinate medially, orbital
      wall laterally, and skull base superiorly. The "vertical component" of the
      surgical box defines the boundaries of the frontal recess and includes the middle
      turbinate and intersinus septum medially, medial orbital wall and orbital roof
      laterally, nasofrontal beak anteriorly, and skull base and posterior table of
      frontal sinus posteriorly. The paranasal sinuses are divided into anterior,
      posterior, and sphenoidal functional cavities based on their distinct drainage
      pathways into the nose. The ultimate goal of surgery is to create a functional
      sinus cavity. Application of the paranasal surgical box and its vertical
      component enables the surgeon to view the limits of dissection with a single
      position of the endoscope. This will ensure complete dissection of the functional
      sinonasal compartments and effectively avoid leaving behind disconnected cells
      from the surgical cavity, mucocele formation, mucous recirculation, overcome
      obstructive phenomenon and enable maximal delivery of topical therapy in the post
      operative setting. This article reviews the structure and function of the nasal
      cartilages and turbinates. It also describes the concept of the paranasal
      surgical box, key anatomical landmarks and limits of dissection. Normal anatomy
      and common variants of normal anatomy are discussed.

PMID- 29021028
TI  - Chapter 2: Nasal obstruction.
AB  - Nasal obstruction is one of the most common presenting symptoms requiring medical
      attention at both the primary care physician and the otorhinolaryngologists'
      level. Nasal obstruction may be caused by anatomic, physiological, or neurologic
      factors. Complexity is added to this situation because, often, the causation may
      be multifactorial. Nasal obstruction is the primary symptom of persistent
      allergic rhinitis (AR) and affects up to 40% of the population. AR must be
      treated throughout the year; thus, treatment choices and patient compliance must
      be considered. It is interesting to note that AR directly affects an individual's
      quality of life, quality of sleep, and workplace efficiency. Therefore, the
      magnitude of costs to both the individual and the society must be recognized.
      Various medical therapies and surgical techniques will be described for the
      treatment of nasal obstruction.

PMID- 29021029
TI  - Chapter 3: Epistaxis.
AB  - Epistaxis is a common problem that may range in severity from a minor nuisance to
      hemodynamically significant bleeding. Vascular anatomy allows for predictable
      identification of suspicious bleeding sites. Historically, packing was the
      workhorse of management, but, currently, more directed interventions have become
      available. These modalities may result in improvements in both cost-effectiveness
      and patient comfort.

PMID- 29021030
TI  - Chapter 4: Chronic rhinosinusitis.
AB  - Chronic rhinosinusitis (CRS) is the second most common chronic medical condition
      in the United States. It represents a group of disorders characterized by
      inflammation of the nasal mucosa and paranasal sinuses of at least 12 weeks
      duration. CRS with or without nasal polyps is defined as inflammation of the nose
      characterized by two or more symptoms, one of which should be either nasal
      blockage, obstruction, congestion, or nasal discharge (anterior/posterior nasal
      drip); with or without facial pain/pressure; and/or with or without reduction or
      loss of smell. Symptomatology should be supported by obvious disease evident in
      either nasal endoscopy or computed tomography imaging. Although CRS is not likely
      to be cured by either medical or surgical therapy, it can generally be
      controlled. Best medical evidence supports maintenance therapy with intranasal
      corticosteroids and saline irrigation. For exacerbations, short to intermediate
      courses of antibiotics (up to 4-weeks) with or without oral corticosteroids are
      recommended. For patients with difficult-to-treat CRS, functional endoscopic
      sinus surgery provides an adjunctive therapeutic option.

PMID- 29021031
TI  - Chapter 5: Pediatric rhinosinusitis: Definitions, diagnosis and management-An
      overview.
AB  - Rhinosinusitis is common in the pediatric population; however, diagnostic and
      management techniques often differ when compared with adult rhinosinusitis.
      Multidisciplinary guidelines have outlined the diagnostic criteria for pediatric
      rhinosinusitis. Although acute rhinosinusitis is a more infectious phenomenon,
      chronic sinusitis involves a more multifactorial etiology. This article outlines
      some of the definitions of rhinosinusitis, diagnosis and management of pediatric
      sinusitis, and the complications of rhinosinusitis seen in the pediatric
      population.

PMID- 29021032
TI  - Chapter 6: Nasal polyps.
AB  - Nasal polyps occur in 1-4% of the population, usually occurring in the setting of
      an underlying local or systemic disease. The most common associated condition is
      chronic rhinosinusitis (CRS). A high prevalence of nasal polyps is also seen in
      allergic fungal rhinosinusitis, aspirin-exacerbated respiratory disease, Churg
      Strauss syndrome, and cystic fibrosis. In the setting of CRS, nasal polyps are
      not likely to be cured by either medical or surgical therapy; however, control is
      generally attainable. The best medical evidence supports the use of intranasal
      corticosteroids for maintenance therapy and short courses of oral corticosteroids
      for exacerbations. The evidence for short- and long-term antibiotics is much less
      robust. For patients with symptomatic nasal polyposis nonresponsive to medical
      therapies, functional endoscopic sinus surgery provides an adjunctive therapeutic
      option.

PMID- 29021033
TI  - Chapter 7: Allergic fungal rhinosinusitis.
AB  - Allergic fungal rhinosinusitis (AFRS) is a type of chronic rhinosinusitis in
      which patients classically exhibit nasal polyps, type I IgE-mediated
      hypersensitivity, characteristic findings on computed tomography scans,
      eosinophilic mucin, and positive fungal stain. New research has sought to further
      understand the pathophysiology of AFRS. However, this has also led to debate
      about the classification and predominance of this interesting disease process.
      Historically, patients with AFRS are immunocompetent. The disease is most
      prevalent in the southeast and south central United States and typically presents
      with sinus pressure, hyposmia, and congestion. Radiographically, cases of AFRS
      have a distinct appearance, often exhibiting unilateral heterogeneously dense
      material, which may erode and expand the paranasal sinus bony walls. Treatment
      typically consists of surgery, sinonasal irrigations, and topical and systemic
      steroids, all with the effort to decrease the fungal load and antigenic response.
      Immunotherapy is also often included in the treatment regimen for AFRS.

PMID- 29021034
TI  - Chapter 8: Invasive fungal rhinosinusitis.
AB  - Invasive fungal rhinosinusitis (IFRS) is a disease of the paranasal sinuses and
      nasal cavity that typically affects immunocompromised patients in the acute
      fulminant form. Early symptoms can often mimic rhinosinusitis, while late
      symptoms can cause significant morbidity and mortality. Swelling and mucosal
      thickening can quickly progress to pale or necrotic tissue in the nasal cavity
      and sinuses, and the disease can rapidly spread and invade the palate, orbit,
      cavernous sinus, cranial nerves, skull base, carotid artery, and brain. IFRS can
      be life threatening if left undiagnosed or untreated. While the acute fulminant
      form of IFRS is the most rapidly progressive and destructive, granulomatous and
      chronic forms also exist. Diagnosis of IFRS often mandates imaging studies in
      conjunction with clinical, endoscopic, and histopathological examination.
      Treatment of IFRS consists of reversing the underlying immunosuppression,
      antifungal therapy, and aggressive surgical debridement. With early diagnosis and
      treatment, IFRS can be treated and increase patient survival.

PMID- 29021035
TI  - Chapter 9: Benign sinonasal neoplasms.
AB  - Benign sinonasal neoplasms are a heterogeneous group of tumors that present with
      similar symptoms including nasal obstruction, anosmia, rhinorrhea, and epistaxis.
      The proper workup and accurate diagnosis is essential for these tumors so that
      the appropriate treatment plan can be established. In this article of benign
      sinonasal neoplasms, we discuss their typical clinical presentation, histological
      and radiographic findings, and treatment options.

PMID- 29021036
TI  - Chapter 10: Sinonasal malignancies.
AB  - Malignant tumors of the sinonasal tract are uncommon tumors of the head and neck.
      Patients often present in the later years of life with unilateral symptoms and
      potential involvement of nearby structures such as the orbit, brain, or cranial
      nerves. Presenting symptoms are similar to patients suffering from inflammatory
      sinonasal disease and thus early diagnosis relies heavily on a high clinical
      suspicion. There are established risk factors based on exposure to the by
      products of woodworking, metal, textile, and leather industries. Sinonasal
      malignancies are generally divided into those of epithelial origin (squamous cell
      carcinoma, adenocarcinoma, and adenoid cystic carcinoma) and nonepithelial origin
      (olfactory neuroblastoma, chondrosarcoma, and mucosal melanoma). Accurate
      histopathology confirmation and staging of the tumor is critical prior to making
      treatment decisions. Both computed tomography and magnetic resonance imaging are
      required to accurately determine the extent of local disease. Treatment is based
      on multimodality therapy, primarily surgical excision, and postoperative
      radiotherapy. This article reviews the classification of malignant tumors of the
      paranasal sinuses, their clinical presentation, relevant diagnostic
      investigations, and the principals of therapy and management.

PMID- 29021037
TI  - Chapter 11: Granulomatous diseases and chronic sinusitis.
AB  - Nasal crusting, rhinitis, and sinusitis are presentations of common conditions;
      however, these can also be the presenting symptoms of an underlying systemic
      disorder such as an infection, malignancy, or granulomatous disease.
      Granulomatous diseases with head and neck manifestations include Wegener's
      granulomatosis, Churg-Strauss syndrome, and sarcoidosis. These diseases are
      managed through a multidisciplinary approach that often includes
      otolaryngologists. This article presents a brief review of granulomatous diseases
      and their rhinologic manifestations and includes relevant diagnostic tests and
      systemic and local treatment options.

PMID- 29021038
TI  - Chapter 12: Surgery for sinonasal disease.
AB  - Surgery for chronic rhinosinusitis is an effective complement to a well-designed
      medical regimen. Functional endoscopic sinus surgery is among the most common
      surgeries performed for sinonasal disease refractory to maximal medical therapy.
      Nasal surgery techniques, such as septoplasty and inferior turbinate surgery, may
      assist in both relieving the symptom of nasal obstruction and providing access
      for sinus surgery. Although rare, open sinus techniques are occasionally
      required.

PMID- 29021039
TI  - Chapter 13: Olfactory disorders.
AB  - Decreased sense of smell can lead to significant impairment of quality of life,
      including taste disturbance and loss of pleasure from eating with resulting
      changes in weight, and difficulty in avoiding health risks such as spoiled food
      or leaking natural gas. Recent epidemiological reports have shown that despite
      fairly low self-reported prevalence of these disorders in large population
      studies, when validated smell identification or threshold tests are used they
      reveal quite a high prevalence of hyposmia and anosmia in certain groups,
      especially the elderly. Several different pathophysiological processes, such as
      head trauma, aging, autoimmunity, and toxic exposures, can contribute to smell
      impairment, with distinct implications concerning prognosis and possible
      treatment. Otolaryngologists are most likely to see this symptom in patients with
      chronic rhinosinusitis, and this now appears to be caused more by the mucosal
      inflammation than by physical airway obstruction.

PMID- 29021040
TI  - Chapter 14: Nonallergic rhinitis.
AB  - Rhinitis is characterized by one or more of the following nasal symptoms:
      congestion, rhinorrhea (anterior and posterior), sneezing, and itching. It is
      classified as allergic or nonallergic, the latter being a diverse syndrome that
      is characterized by symptoms of rhinitis that are not the result of IgE-mediated
      events. Excluding infectious rhinitis and underlying systemic diseases, clinical
      entities that can be classified among the disorders that make up the nonallergic
      rhinitis syndromes include gustatory rhinitis, nonallergic rhinitis with
      eosinophilia syndrome (NARES), atrophic, drug-induced (rhinitis medicamentosa),
      hormone induced, senile rhinitis (of the elderly), rhinitis associated with
      chronic rhinosinusitis with or without nasal polyps, and the idiopathic variant
      formerly known as vasomotor rhinitis but more accurately denoted as nonallergic
      rhinopathy (NAR). The prevalence of nonallergic rhinitis has been observed to be
      one-third that of allergic rhinitis, affecting ~7% of the U.S. population or ~22
      million people. NAR is the most common of the nonallergic rhinitis subtypes,
      comprising at least two-thirds of all nonallergic rhinitis sufferers. Although
      certain precipitants such as perfume, strong odors, changes in temperature or
      humidity, and exposure to tobacco smoke are frequently identified as symptom
      triggers, NAR may occur in the absence of defined triggers. The diagnosis of
      nonallergic rhinitis is purely clinical and relies on a detailed history and
      physical exam. Skin testing or in vitro testing to seasonal and perennial
      aeroallergens is required to make the diagnosis of nonallergic rhinitis. Because
      of the heterogeneous nature of this group of disorders, treatment should be
      individualized to the patient's underlying pathophysiology and/or symptoms and is
      often empiric.

PMID- 29021041
TI  - Chapter 15: Allergic rhinitis.
AB  - Allergic rhinitis affects 60 million of the U.S. population, 1.4 billion of the
      global population, and its prevalence appears to be increasing. The duration and
      severity of allergic rhinitis symptoms place a substantial burden on patient's
      quality of life, sleep, work productivity, and activity. The health impact of
      allergic rhinitis is compounded by associated complications and comorbidities
      including asthma, otitis media, sinusitis, and nasal polyps. Allergic rhinitis
      symptoms result from a complex, allergen-driven mucosal inflammatory process,
      modulated by immunoglobulin E (IgE), and caused by interplay between resident and
      infiltrating inflammatory cells and a number of vasoactive and proinflammatory
      mediators, including cytokines. This allergic response may be characterized as
      three phases: IgE sensitization, allergen challenge, and elicitation of symptoms.
      A thorough allergic history is the best tool for the diagnosis of allergic
      rhinitis, the establishment of which is achieved by correlating the patient's
      history and physical exam with an assessment for the presence of specific IgE
      antibodies to relevant aeroallergens determined by skin testing or by in vitro
      assay. Management of allergic rhinitis includes modifying environmental
      exposures, implementing pharmacotherapy, and, in select cases, administering
      allergen-specific immunotherapy. Intranasal therapeutic options include
      antihistamines, anticholinergic agents, corticosteroids (aqueous or aerosol),
      mast cell stabilizers, saline, and brief courses of decongestants. Selection of
      pharmacotherapy is based on the severity and chronicity of symptoms with the most
      effective medications being intranasal corticosteroids and intranasal
      antihistamines, which can be used in combination (separately or in fixed dose)
      for more difficult to control allergic rhinitis.

PMID- 29021042
TI  - Chapter 16: Determining the role of allergy in sinonasal disease.
AB  - The contributing role of specific IgE sensitization in the pathophysiology of
      sinonasal diseases including rhinitis, chronic rhinosinusitis (CRS), and nasal
      polyps is explored. Although it is estimated that sensitization to environmental
      allergens is present in 75% of patients with rhinitis, the role of allergy in CRS
      and nasal polyps is less certain. However, when atopy is present in the setting
      of nasal polyps, it is associated with worse quality of life and a higher
      incidence of asthma. Several theories have been put forth whereby inhalant
      aeroallergen exposure could drive the inflammatory response that occurs both in
      the nose and in the sinuses. Tools available to determine the presence of
      allergic sensitization include skin tests for immediate hypersensitivity, in
      vitro testing for allergen-specific IgE, and nasal allergen provocation testing.
      Whether by skin testing or in vitro testing, the identification of specific IgE
      requires clinical correlation with the history and physical exam.

PMID- 29021043
TI  - Chapter 17: Immunomodulation of allergic sinonasal disease.
AB  - IgE hypersensitivity is important to the pathogenesis of allergic diseases and
      the development and persistence of airway inflammation. Allergic immunomodulation
      encompasses various therapies that attempt to suppress or modify the immune
      mechanisms responsible for IgE-mediated disease. These include allergy
      immunotherapy (AIT) in the forms of subcutaneous immunotherapy (SCIT) and
      sublingual immunotherapy (SLIT), as well as the emergence of biological agents,
      such as anti-IgE, for allergic respiratory disease. Clinical evidence strongly
      supports the efficacy and safety of AIT for the treatment of allergic rhinitis,
      allergic conjunctivitis, and allergic asthma, but for chronic rhinosinusitis
      evidence is lacking. In allergic rhinitis, the decision to initiate AIT depends
      on the degree to which symptoms can be reduced by avoidance and medication, the
      amount and type of medication required to control symptoms, the adverse effects
      of medication, the severity and duration of symptoms, and their effect on quality
      of life. AIT has the potential to produce sustained long-lasting immune
      modulation and possibly avoid or reduce lifelong requirements for medical
      therapy. Although SLIT is currently being evaluated, SCIT remains the preferred
      form of AIT in the United States because of robust efficacy data, availability of
      allergen extracts, and current Food and Drug Administration approval. However,
      SLIT holds the potential for greater patient safety and convenience. Other
      immunomodulators such as anti-IgE also hold promise, but require further
      investigation.

PMID- 29021044
TI  - Topical mitomycin C as an adjunct to surgical debulking and medical treatment in
      rhinoscleroma.
AB  - BACKGROUND: Rhinoscleroma is a chronic granuloma that is endemic in Egypt and is
      caused by gram-negative bacilli (Klebsiella rhinoscleromatis). The nasal mucosa
      is affected in almost all cases, which causes nasal obstruction, anosmia, and
      epistaxis. The disease usually passes through an atrophic stage (atrophic
      rhinitis) and a granulomatous stage before ending in the fibrotic stage, with
      possible bone destruction. OBJECTIVE: This study assessed the effect of topical
      mitomycin C (MMC) on reducing the recurrence of granulation tissue and intranasal
      adhesions after endoscopic debulking and continuous medical treatment of nasal
      rhinoscleroma. MATERIALS AND METHODS: This double-blind randomized clinical trial
      was performed with 30 patients who had rhinoscleroma (granulomatous and fibrotic
      stages). At the end of endoscopic debulking, meshes impregnated with MMC was
      placed in one nasal cavity for 5 minutes, while another meshes impregnated with
      saline solution were placed in the opposite side. Repeated meshes with MMC were
      placed in the same side during the follow-up period. Patients were followed up
      for 1 year. The recurrence of granulation tissue and the degree of intranasal
      adhesions were recorded and compared according to the Lund-Kennedy score.
      RESULTS: At 12 months' follow-up, among the total 30 patients, 30 MMC sides were
      compared with 30 control sides: 69% of MMC sides versus 32% of control sides had
      no recurrence of granulation tissue (p = 0.01) and 65% of MMC sides versus 24% of
      control sides had no recurrence of intranasal adhesions (p = 0.03). The Lund
      Kennedy score decreased from 2.1 +/- 0.64 to 0.8 +/- 0.41 and from 2.3 +/- 0.33
      to 1.9 +/- 0.20 in the MMC sides and control sides, respectively, with a
      nonstatistically significant lower incidence of intranasal adhesions in the MMC
      sides. CONCLUSION: Topical MMC may reduce granulation tissue and intranasal
      adhesion formation in patients with rhinoscleroma. Further studies with a larger
      number of samples and longer follow-up periods are recommended.

PMID- 29021045
TI  - Malpractice in Treatment of Sinonasal Disease by Otolaryngologists: A Review of
      the Past 10 Years.

PMID- 29021047
TI  - Erratum.

PMID- 29021046
TI  - The utility of magnetic resonance imaging in the diagnostic evaluation of
      idiopathic olfactory loss.

PMID- 29021048
TI  - Unplanned Revisions and Readmissions After Ambulatory Sinonasal Surgery.

PMID- 29021049
TI  - CD4+ and CD8+ regulatory T cells in chronic rhinosinusitis mucosa.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) mucosal inflammation is characterized by
      an accumulation of effector-memory T cells, but their immune regulatory potential
      has not been adequately examined. Coexpression of transcription factor, forkhead
      box P3 (Foxp3), and interleukin-2 receptor, CD25, in CD4+ and CD8+ T cells is
      linked with regulatory function in humans. The aim of this study was to
      investigate the regulatory T cell (Treg) phenotype of CD4+ (CD4Treg) and CD8+
      (CD8Treg) T cells in peripheral blood (PB) and sinus mucosa of CRS patients.
      METHODS: Prospective study was performed involving 32 CRS with nasal polyp
      (CRSwNP), 14 CRS without nasal polyp (CRSsNP), and 8 control patients. Sinus and
      PB T lymphocytes were stained with CD3, CD4, CD8, CD25, and Foxp3 and analyzed
      using flow cytometry. Relevant clinical characteristics, sinus bacterial culture
      results, and eosinophilic mucus were examined. RESULTS: Sinus mucosa had a higher
      percentage of CD4Treg (CD3+CD4+CD25+Foxp3+) population compared with PB in all
      patients. The percentage of PB CD4Treg and CD8Treg (CD3+CD8+CD25+Foxp3+) was not
      significantly different between the study groups. CRS mucosal tissue had a higher
      percentage of CD4Treg and activated T-helper cells than controls. There was no
      significant difference in PB and mucosal CD4Treg populations in CRS patients
      based on the presence of allergy, sinus culture results, or eosinophilic mucus.
      In controls, increased mucosal CD4Treg correlated with coexisting allergy.
      Although overall CD4Treg numbers were higher, the regulatory potential of
      activated CD4+ T cells (CD4Treg/activated T-helper cell ratio) was significantly
      lower in CRS mucosa compared with controls. The CD8Treg subset was also
      significantly reduced in CRSwNP mucosa compared with controls. CONCLUSION: A
      higher percentage of CD4Treg and activated T-helper cells in CRS mucosa suggests
      increased inflammation in CRS, independent of the presence of allergy, microbial
      culture results, or eosinophilic mucus. However, the decreased ratio of CD4Treg
      versus activated T-helper cells in CRS and reduced CD8Treg population in CRSwNPs
      indicates an inflammatory bias and the inability to control mucosal disease.

PMID- 29021050
TI  - Assessing the relationship between serum resistin and nasal obstruction in
      children with allergic rhinitis.
AB  - BACKGROUND: Nasal obstruction has been reported as a "key symptom" of allergic
      rhinitis (AR) because it is deeply associated with impaired quality of life and
      it reflects more directly the allergic inflammation in the nasal mucosa. Resistin
      is known to be involved in inflammatory processes exerting an important role in
      the regulation of cytokine production even though its effective proinflammatory
      activity at nasal level has never been fully established. This study investigates
      the relationship between resistin levels and nasal obstruction assessed by an
      objective method such as active anterior rhinomanometry. METHODS: Fifty-three
      children between 4 and 10 years of age affected by persistent allergic rhinitis
      (PAR) were enrolled and subdivided in two groups. Serum resistin levels were
      detected in all children. The same day patients underwent rhinomanometry, which
      was considered negative (no nasal obstruction) when the fraction of predicted
      values (p.v.'s) was between 71 and 100% and it was considered positive when the
      fraction of p.v. was <=70%. RESULTS: The serum resistin levels were significantly
      higher in children with moderate-severe PAR than in patients with mild PAR (p <
      0.03). Furthermore, serum resistin levels were significantly higher in children
      with positive rhinomanometry compared with negative rhinomanometry (p < 0.03).
      The fraction of p.v.'s of nasal flows in patients with nasal obstruction had a
      significant negative correlation with serum resistin levels (p < 0.001).
      CONCLUSION: This study provides evidence that resistin levels are increased in
      children with severe nasal obstruction measured by an objective and quantitative
      approach.

PMID- 29021051
TI  - Rhinology fellowship training and its scholarly impact.
AB  - BACKGROUND: Previous examination of the impact of fellowship training on
      scholarly productivity among otolaryngologists found that head and neck surgeons
      and otologists had a higher mean h-index than fellowship-trained rhinologists.
      Because fellowship training in rhinology is a historically newer trend, the
      objectives of the present analysis were to further characterize research
      productivity among fellowship-trained academic rhinologists, including geographic
      and temporal trends, to gain insight into the future direction of scholarly
      pursuits within the field. METHODS: Fellowship-trained rhinologists in academic
      practices were identified from the American Rhinologic Society online listings
      and organized by academic rank, number of years in practice, location, and h
      index, as calculated using the Scopus database. RESULTS: Mean h-index rose with
      increasing years in practice after fellowship. The h-index, number of
      publications, and the E-factor (a newly described bibliometric) increased with
      successive academic rank. The E-factor for rhinologists in this current analysis
      was not statistically different from the values calculated for other
      otolaryngology subspecialties (p > 0.05). CONCLUSION: Fellowship-training in
      rhinology is a relatively recent development, with half of the academic
      rhinologists included in this analysis having completed fellowship training
      within the past 5 years. Scholarly productivity among academic rhinologists
      increases with academic seniority. As the current cohort of fellowship-trained
      rhinologists progress in their academic careers, previously described deficits in
      scholarly productivity relative to other subspecialties are expected to diminish.

PMID- 29021052
TI  - Erratum.

PMID- 29021053
TI  - Olfactory bulb volume changes in patients with sinonasal polyposis: a magnetic
      resonance imaging study.

PMID- 29021054
TI  - Smell and taste in patients with vascular malformation of the extracranial head
      and neck region.
AB  - BACKGROUND: Olfactory and gustatory functions have not been investigated in
      patients with vascular malformation of the extracranial head and neck region with
      validated smell and taste tests. Although olfactory and gustatory deficiencies
      are often not outwardly apparent, they substantially affect daily life. METHODS:
      Smell and taste tests using sniffin sticks and taste strips were administered in
      40 patients. RESULTS: For all age groups and both sexes, odor threshold (THR)
      values were, on average, lower in patients than in healthy individuals; whereas,
      values of odor identification and discrimination were not significantly lower.
      Regarding odor THR, 33 (82.5%) patients were hyposmic. Taste values (sweet, sour,
      salty, bitter, and total taste) were, on average, lower in patients than in
      healthy individuals; 21 (52.5%) patients were hypogeusic. Disease duration did
      not correlate with smell and taste test values. Patients with and without tongue
      involvement had decreased odor threshold and taste values. No significant
      differences were identified when taste values on the left and right sides of the
      tongue were compared in patients without tongue involvement and with unilateral
      and bilateral tongue involvement. Patients with venous malformations had lower
      smell test values, and patients with lymphatic malformations had lower taste test
      values than patients with other malformations. CONCLUSION: Patients exhibit
      significantly reduced olfactory and gustatory function even when the nose and/or
      tongue are not malformed. Patients should be tested with validated smell and
      taste tests to adequately inform and advise them about overcoming smell and taste
      deficits.

PMID- 29021055
TI  - The link between rhinitis and rapid-eye-movement sleep breathing disturbances in
      children with obstructive sleep apnea.
AB  - BACKGROUND: Rhinitis and obstructive sleep apnea (OSA) often coexist during
      childhood. To delineate this clinical association, we examined OSA severity and
      polysomnogram (PSG) features in children with rhinitis and OSA. Given that rapid
      eye-movement (REM) sleep is characterized by nasal congestion, we hypothesized
      that children with rhinitis have more REM-related breathing abnormalities.
      METHODS: We conducted a retrospective cross-sectional analysis of 145 children
      with PSG-diagnosed OSA. Outcomes included PSG parameters and obstructive apnea
      hypopnea index (OAHI) during REM and non-REM. Linear multivariable models
      examined the joint effect of rhinitis and OSA parameters with control for
      potential confounders. RESULTS: Rhinitis was present in 43% of children with OSA
      (n = 63) but overall OAHI severity was unaffected by the presence of rhinitis. In
      contrast, OAHI during REM sleep in children with moderate-severe OSA was
      significantly increased in subjects with rhinitis and OSA (44.1/hr; SE = 6.4)
      compared with those with OSA alone (28.2/hr; SE = 3.8). CONCLUSION: Rhinitis is
      highly prevalent in children with OSA. Although OSA is not more severe in
      children with rhinitis, they do have a distinct OSA phenotype characterized by
      more REM-related OSA. Further research is needed to delineate the link between
      REM-sleep and the physiology of the nose during health and disease.

PMID- 29021057
TI  - Erratum.

PMID- 29021056
TI  - Erratum.

PMID- 29021058
TI  - A randomized trial of mupirocin sinonasal rinses versus saline in surgically
      recalcitrant staphylococcal chronic rhinosinusitis.

PMID- 29021062
TI  - Erratum.

PMID- 29021063
TI  - Erratum.

PMID- 29021064
TI  - Management of non-invasive rhinosinusitis in the immunosuppressed patient
      population.

PMID- 29021065
TI  - Factors Affecting Time to Revision Sinus Surgery for Nasal Polyps: A 25-Year
      Experience.

PMID- 29021066
TI  - Histological features of the nasal mucosa in hematopoietic stem cell
      transplantation.
AB  - BACKGROUND: Immunosuppression is the leading cause of recurrent sinus infections
      after hematopoietic stem cell transplant (HSCT), with increased incidence of
      sinusitis in patients with chronic graft versus host disease (GVHD). Histological
      descriptions of the oral mucosa, lung ciliary epithelium, and intestinal mucosa
      related to HSCT have been described. However, few have described the nasal
      mucosa. We, therefore, sought to elucidate the histological and ultrastructural
      features of the nasal mucosa in patients after HSCT to better understand the
      pathophysiology of the immune response. METHODS: Uncinate processes from 24 HSCT
      patients and 12 immunocompetent patients were subjected to histological analyses
      via light and transmission electron microscopy (TEM). RESULTS: TEM revealed
      aberrant cilia structure, altered mitochondria quantity, microvilli, and
      cytoplasm vacuolization. All HSCT patients with rhinosinusitis had significant
      loss or absence of cilia (p = 0.018). Apoptotic bodies were increased and Goblet
      cells decreased in nasal epithelium from patients with chronic GVHD (p = 0.04).
      CONCLUSION: This tissue destruction likely enhances pathogen penetration
      resulting in recurrent infection.

PMID- 29021067
TI  - Spirometric parameters and levels of interferon gamma and IL-5 in induced sputum
      from patients with allergic rhinitis or asthma.
AB  - BACKGROUND: This study was designed to analyze spirometric parameters and
      cytokine (interferon [IFN] gamma and IL-5) levels in induced sputum from patients
      with asthma or allergic rhinitis (AR) and nonatopic subjects. METHODS: Thirty
      three subjects aged 18-60 years were enrolled in the present study. Eight
      patients had asthma without AR symptoms, 16 had AR without asthma symptoms or
      history, and both groups had positive skin-prick test (SPT) to aeroallergens. The
      nine remaining subjects were healthy nonatopic subjects with negative SPT to
      aeroallergens. Spirometry was performed by evaluating the forced vital capacity
      (FVC), forced expiratory volume in the 1st second (FEV1), and forced expiratory
      flow between 25 and 75% (FEF25-75) of FVC before and after bronchodilator use.
      Induced sputum samples were also collected for measuring cytokine (IFN-gamma and
      IL-5) levels by enzyme-linked immunosorbent assay. RESULTS: Significant pre- and
      postbronchodilator change was observed only for FEV1 with higher variation values
      in asthmatic subjects compared with patients with AR (p < 0.05) and nonatopic
      subjects (p < 0.01). There was no significant difference in pre- and
      postbronchodilator spirometric parameters among the three groups, although
      asthmatic patients showed lower prebronchodilator FEF25-75 values (p = 0.065). IL
      5 levels were higher in induced sputum from patients with asthma and AR compared
      with nonatopic subjects (p = 0.020 and p = 0.032, respectively), but IFN-gamma
      levels showed no significant difference between the groups. CONCLUSION:
      Spirometric measurements were not able to show any occurrence of bronchial
      constriction in patients with AR, but predominant IL-5 levels in induced sputum
      from these patients reinforce the role of Th2-type immune response in lower
      respiratory airways that could contribute to the concept of "one airway, one
      disease."

PMID- 29021068
TI  - Efficacy of intranasal bevacizumab (avastin) treatment in patients with
      hereditary hemorrhagic telangiectasia-associated epistaxis.

PMID- 29021069
TI  - Abstracts from the North American Rhinology & Allergy Conference, February 3,
      2011, Puerto Rico.
AB  - INTRODUCTION: To establish the efficacy of bepotastine besilate ophthalmic
      solution (bepotastine) 1.5%, a dual acting histamine H1 receptor antagonist
      approved for treatment of ocular itching associated with allergic conjunctivitis,
      compared to placebo in relieving ocular itching and redness for subjects with
      active allergic rhinoconjunctivitis. METHODS: A randomized, double-masked,
      placebo-controlled, confirmatory natural exposure study of bepotastine 1.5% and
      placebo was conducted during allergy season at 12 clinical sites throughout the
      U.S. Following a 7-day screening period, eligible subjects >=12 years old were
      assigned in a 1:1 ratio to dosing OU b.i.d. either bepotastine 1.5% (n = 123) or
      placebo (n = 122). Subjects recorded instantaneous grades for their ocular
      symptoms prior to their next dose for 14 consecutive days. Clinically significant
      reduction in ocular sign or symptom grades between treatment groups required p <=
      0.05 as determined by ANCOVA analysis. RESULTS: Significant clinical
      effectiveness with bepotastine 1.5% was demonstrated over the 2-week treatment
      period in comparison to placebo in the intent-to-treat population for reducing
      mean instantaneous grades for both ocular itching (p = 0.007) and redness (p =
      0.001). Investigator rating of efficacy over the 2-week treatment period across
      response categories was also superior for bepotastine 1.5% compared to placebo (p
      = 0.024). Only one subject discontinued participation in the study due to an
      adverse event. CONCLUSIONS: These data support bepotastine 1.5% as an effective
      treatment for allergen-induced signs and symptoms in a clinical study designed to
      closely resemble the conditions under which patients with allergic
      rhinoconjunctivitis would require treatment.

PMID- 29021070
TI  - Treatment of Postviral Olfactory Loss with Glococorticoids, Ginko biloba, and
      Mometasone Nasal Spray.

PMID- 29021071
TI  - Manuka honey: Histological effect on respiratory mucosa.

PMID- 29021072
TI  - The interaction between bacteria and mucosal immunity in chronic rhinosinusitis:
      A prospective cross-sectional analysis.
AB  - BACKGROUND: We have detected intramucosal bacteria within the sinus mucosa of
      patients with chronic rhinosinusitis (CRS), but our attempts at characterizing
      these did not yield any discernible genotypic or phenotypic differences from
      surface bacteria. We hypothesized that the presence of intramucosal microcolonies
      reflected host mucosal immune dysfunction. This study characterizes the
      activation status of T cells, B cells, and macrophages in the sinus mucosa of
      patients with CRS and controls and determines the impact of bacteria on mucosal
      immunology. METHODS: Swabs and mucosal biopsy specimens were taken from 27
      patients with CRS undergoing sinus surgery and 9 patients with normal sinuses
      having transnasal pituitary surgery. Microcolonies were detected using Gram
      staining, and the immune cells were characterized by immunohistochemical
      techniques. RESULTS: Swab culture rates for Staphylococcus aureus were similar
      between CRS and controls. However, there were significantly more intramucosal
      microcolonies in CRS (59% versus 11%) than in controls (p = 0.02). There were
      significantly more immune cells in CRS. Percentage of activated T and B cells
      were similar between CRS and controls, but there were significantly more CD163+
      M2 macrophages in patients with CRS (p = 0.0004). Furthermore, percentage of
      CD163+ macrophages showed a positive correlation with disease severity. The
      presence of bacteria had no impact on immunology or disease severity. CONCLUSION:
      Tolerance of intramucosal microcolonies in CRS may reflect altered macrophage
      function in the host mucosa. The clinical severity of CRS is also dependent on
      the host mucosa immune dysfunction, rather than the presence of intramucosal
      microcolonies.

PMID- 29021073
TI  - Increased body mass index and bronchial impairment in allergic rhinitis.
AB  - BACKGROUND: Several studies have outlined a possible relationship between an
      increased body mass index (BMI) and respiratory allergic diseases, such as asthma
      and allergic rhinitis (AR). The aim of this study was to analyze the relationship
      among BMI, spirometry, bronchial hyperreactivity (BHR), and fractional
      concentration of exhaled nitric oxide (FeNO) in a cohort of AR patients. METHODS:
      The study included 155 patients with persistent AR alone and 155 healthy
      controls. All subjects were evaluated performing skin-prick test, spirometry,
      bronchoprovocation test with methacholine, and FeNO measurement. RESULTS: BMI
      values were significantly higher in AR patients than in control subjects (p =
      0.038). Overweight/obese AR patients had more altered functional and inflammatory
      parameters than normal weight patients. BMI > 25 is a risk factor for (i) early
      bronchial airflow limitation (odds ratio [OR], 3.81), (ii) high FeNO values (OR,
      1.96), and BHR (OR, 3.29). CONCLUSIONS: The present study may suggest that BMI
      assessment should be routinely considered in AR patients for assessing risk for
      early bronchial impairment, such as suggesting possible evolution to asthma.

PMID- 29021075
TI  - Rhinogenic Laryngitis, Cough, and the Unified Airway.

PMID- 29021074
TI  - Editorial.

PMID- 29021076
TI  - Erratum.

PMID- 29021077
TI  - Survival outcomes in acute invasive fungal sinusitis: A systematic review and
      quantitative synthesis of published evidence.

PMID- 29021078
TI  - Sexual (dys)functioning is related to drive for thinness, not drive for
      muscularity.
AB  - : Background Negative body image can result in sexual dysfunction for both women
      and men. Drive for thinness, drive for muscularity and drive for leanness have
      all been associated with poor body image. However, research to date has not
      examined which is the strongest predictor of sexual problems in each gender.
      METHODS: The present study used measures of drive for muscularity and drive for
      thinness simultaneously to predict sexual functioning in both genders.
      Participants (n=519) completed measures of drive for thinness, drive for
      muscularity, sexual esteem, sexual assertiveness, discomfort exposing their
      bodies during sex and genital satisfaction. The interaction between drive for
      thinness and drive for muscularity was used to approximate drive for leanness.
      RESULTS: Drive for thinness, not drive for muscularity (or any combination of the
      two), predicted men's and women's sexual problems. CONCLUSIONS: We add to the
      growing body of literature on the destructive nature of excessive drive for
      thinness, and highlight that it may be a core factor in promoting and maintaining
      men's (as well as women's) sexual problems.

PMID- 29021079
TI  - Blood-borne virus transmission in an urban, culturally diverse neighbourhood:
      results from a cross-sectional bio-behavioural survey using innovative outreach
      methods in a hard-to-reach population.
AB  - : Background Following a HIV outbreak among Aboriginal people in a culturally
      diverse inner-city suburb of Melbourne, a blood-borne virus (BBV) screening
      program was conducted to inform public health interventions to prevent
      transmission and facilitate timely diagnosis and linkage to care. METHODS: In
      August-September 2014, community health workers recruited people who inject drugs
      (PWID) from a local needle and syringe program. Participants were tested for
      hepatitis C virus (HCV), hepatitis B virus (HBV), HIV and syphilis and completed
      a bio-behavioural questionnaire. RESULTS: In total, 128 PWID participated in the
      study. Serological evidence of exposure to HCV and HBV was detected among 118
      (93%) and 57 participants (45%) respectively. Five participants were HIV
      positive. Independent risk factors for needle sharing were Aboriginality
      (AOR=6.21, P<0.001), attending health care for mental health problems (AOR=2.79,
      P=0.023) and inability to access drug treatment in the previous 6 months
      (AOR=4.34, P=0.023). CONCLUSIONS: BBV prevalence in this sample was much higher
      than reported in other recent Australian studies. This local population is at
      high risk of further BBV transmission, particularly Aboriginal PWID. Individual
      and service-related factors associated with risk in the context of a dynamic
      urban drug culture and HIV outbreak suggest an urgent need for tailored harm
      reduction measures.

PMID- 29021080
TI  - Substantial increase in yield of Neisseria gonorrhoeae testing 2008-2013 at a
      Sydney metropolitan sexual health clinic: an observational study.
AB  - : Background A substantial increase in gonorrhoea notifications in New South
      Wales has been observed in recent years. METHODS: We assessed yield of testing
      and characteristics of those diagnosed with gonorrhoea from January 2008 to
      December 2013 at RPA Sexual Health in the inner-west of Sydney. Yield was defined
      as the proportion of testing occasions which were positive for gonorrhoea.
      Generalised estimating equations were used to calculate trends in yield over
      time. RESULTS: During the 6-year study period, 6456 individuals (4308 males, 2124
      females, 24 transgender individuals) were tested on 12799 occasions; this
      included 2441 gay and bisexual men (GBM) who were tested on 6945 occasions. Over
      the study period there was a significant increase in testing at genital,
      anorectal and pharyngeal sites (P-trend <0.001 for all). In total, gonorrhoea was
      detected on 668 testing occasions among 536 individuals (5.2%). Overall,
      254/12765 (2.0%) of genital tests, 251/7326 (3.4%) of anorectal tests and
      342/8252 (4.1%) of pharyngeal tests were positive. There was a significant
      increase in overall gonorrhoea yield from 2.2% in 2008 to 7.1% in 2013 (P-trend
      <0.001). This temporal increase in gonorrhoea yield was observed in heterosexual
      males (P<0.001), heterosexual females (P-trend=0.008), female sex workers (P
      trend=0.006), HIV-positive GBM and HIV-negative GBM (both P<0.001) and at all
      anatomical sites (P-trend <0.001 for all). CONCLUSIONS: From 2008 to 2013, we
      observed a greater than threefold increase in yield of gonorrhoea testing
      disproportionately affecting GBM, although the increase also occurred in other
      subpopulations and at all anatomic sites. More frequent and comprehensive testing
      could potentially reduce the high and increasing community prevalence of
      gonorrhoea.

PMID- 29021081
TI  - Room at the top.
AB  - Five years after eLife published its first papers, we reflect on our consultative
      approach to peer review, the challenges of reproducibility, and the need to
      reform how published research is assessed.

PMID- 29021082
TI  - Habitat associations of an expanding native alga.
AB  - There are many examples of native macrophytes becoming locally dominant and
      spreading outside their traditional distributions, but the causes and impacts are
      often not understood. In New South Wales, Australia, the green alga Caulerpa
      filiformis is undergoing a range expansion and has transitioned from a
      subdominant to a dominant alga on several rocky shores around the Sydney
      coastline. Here we investigated relationships between established patches of C.
      filiformis, the habitat it occupies and associated algal communities at multiple
      subtidal sites over the green alga's 700 km range. We tested the following
      predictions: 1) C. filiformis cover differs among substrata, being greatest on
      turf-forming algae; 2) C. filiformis cover is positively related to environmental
      variables linked to increased sedimentation (e.g. reduced reef width, surface
      slope, increased rugosity and distance from shore); 3) occurrence of C.
      filiformis is associated with a change in macrophyte community structure and a
      reduction of macrophyte richness; 4) intact native algal canopies inhibit C.
      filiformis spread, but turf-forming algae and bare sand are susceptible to
      invasion. Substratum associations were highly consistent among sites, but
      contrary to our prediction, C. filiformis was most commonly associated with rock
      or rock + sand substratum and less frequently associated with turf-forming algae
      substratum. C. filiformis cover was negatively correlated with reef width, which
      explained most of the variation observed, although local scale variables distance
      from shore, reef slope, and water depth were also correlated with C. filiformis
      cover. Algal diversity and community composition typically differed in the
      presence of C. filiformis, often with a reduction of algal abundances, in
      particular Sargassum spp., although results varied among substrata and sites.
      However, monitoring of borders suggested that C. filiformis does not invade and
      outcompete undisturbed adjacent canopy-forming algae over a 12 month period. Our
      results suggest that disturbance processes (possibly linked to sedimentation)
      acting at the site and quadrat scale are likely important determinants of C.
      filiformis cover and spread, and hence its potential ecological impacts.

PMID- 29021083
TI  - Fertility-preserving surgery for advanced stage ovarian germ cell tumors.
AB  - OBJECTIVE: To evaluate the prevalence and safety of uterine preservation among
      premenopausal women diagnosed with a malignant ovarian germ-cell tumor (MOGCT) of
      advanced stage (stage II-IV). MATERIALS AND METHODS: The National Cancer Database
      was accessed and a cohort of women aged <40years, diagnosed with a MOGCT were
      identified. Those with stage II-IV disease who underwent cancer-directed surgery
      and received chemotherapy were selected for further analysis. Performance of
      hysterectomy was assessed from site-specific surgery codes. Overall survival (OS)
      was determined following generation of Kaplan-Meier curves and compared with the
      log-rank test. A Cox multivariate model was constructed to control for possible
      confounders. RESULTS: A total of 526 eligible patients were identified; rate of
      hysterectomy was 20.2%. Women who had a hysterectomy were older (median age 30.5
      vs 20years, p<0.001) and more likely to present with bilateral tumors (12.6% vs
      3.8%, p<0.001). No differences were noted based on tumor histology (p=0.67). Rate
      of uterine preservation was 82.8%, 79.5% and 75% for those with stage II, III and
      IV disease respectively (p=0.46). There was no difference in OS between women who
      had hysterectomy and those who did not (p=0.051); five-year OS rates were 87.1%
      and 94.4% respectively. After controlling for disease stage, tumor histology and
      patient race, uterine preservation was not associated with a decreased survival
      (HR: 0.59, 95% CI: 0.28, 1.24, p=0.19). CONCLUSIONS: Uterine preservation was not
      associated with decreased survival and should be considered in women with
      advanced stage GCTs interested in future fertility.

PMID- 29021084
TI  - Association between Epstein-Barr virus (EBV) and cervical carcinoma: A meta
      analysis.
AB  - OBJECTIVES: Human papillomavirus (HPV) has been implicated as a major factor in
      cervical carcinogenesis. However, many pieces of evidence gathered over the last
      two decades suggest Epstein-Barr virus (EBV) plays a secondary role in this
      process. The purpose of the present meta-analysis was to determine whether the
      presence of EBV infection increases the risk of cervical carcinoma. METHODS:
      Based on 25 articles, the analysis yielded a 33.44% overall pooled prevalence of
      EBV. RESULTS: The pooled prevalence was higher in patients with carcinoma
      (43.63%) than in healthy patients (19.0%) or patients with cervical
      intraepithelial neoplasia 1 (CIN1) (27.34%) or CIN2/3 (34.67%). Co-infection with
      EBV and HPV displayed a similar pattern. EBV infection was significantly and
      positively associated with lesion grade in cervical epithelia and was more
      prevalent in malignant lesions. Moreover, cervical carcinoma occurred four times
      as often among EBV positive women as in women without EBV infection (OR=4.01
      [1.87-8.58]; p<0.001). CONCLUSIONS: The existence of EBV(+)HPV(-) carcinomas, the
      confirmed expression of latent oncoproteins (EBNA1, EBNA2, LMP1) and EBERs in
      tumor cells, and the association of EBV with the integration of high-risk-HPV DNA
      in malignant specimens point to EBV as a co-factor (so far underestimated) in the
      genesis and/or progression of cervical carcinoma. However, further studies are
      necessary before the link between EBV and cervical carcinoma can be established.

PMID- 29021085
TI  - Fast in situ gamma spectroscopy using hand-held spectrometer with NaI probe.
AB  - In this work a hand-held spectrometer InSpector 1000 with NaI (Tl) 2" x 2"
      detector has been adapted to fast in situ gamma-ray spectroscopy. Two specially
      designed mounting stands with shielding have been built, allowing conducting
      measurements in different geometries. Three particular geometries (NW, IS50,
      IS00) have been chosen for efficiency calibration and further study. The first
      one (NW) is intended for small environmental samples (volume ca 140 cm3)
      collected on site. IS50 geometry is a typical in situ geometry meant for
      radioactivity measurements in soil with detector pointed towards the ground. In
      this geometry the probe is shielded and mounted 50 cm above the soil surface. The
      new proposed geometry IS00 is designed in the way that the detector is inserted
      directly into the soil in order to increase the counting efficiency. The methods
      of efficiency calibration involved using calibration standards (in NW geometry)
      and the results obtained in previous in situ measurements with InSpector 2000
      portable spectrometer with HPGe detector and ISOCSTM Shield Systems, which is
      routinely used in environmental measurements. NW geometry turned out to be useful
      for natural radioisotopes concentrations (K-40, U-238 and Th-232), which
      significantly exceed typical values of those concentrations observed in Poland.
      Both IS50 and IS00 geometries are applicative for quick (2 h long measurement)
      evaluation of typical concentrations of K, U and Th in soils. The newly proposed
      geometry IS00 is superior as it showed lower detection limits and uncertainties
      as well as its handling was far easier than of IS50. Authors have proven that
      hand-held spectrometer InSpector 1000, together with mounting stands and
      shielding, can be successfully used for fast in situ gamma-spectroscopy. Its
      relatively small weight and good mobility are additional assets. Moreover,
      detailed procedures for measurements in each geometry have been developed to
      conduct such analyses properly.

PMID- 29021086
TI  - Genomic characterization of an extensively drug-resistant KPC-2-producing
      Klebsiella pneumoniae ST855 (CC258) only susceptible to ceftazidime-avibactam
      isolated in Brazil.
AB  - In this study, we describe the genetic features of an XDR KPC-2-producing
      Klebsiella pneumoniae isolate by using whole-genome sequencing, its clinical
      epidemiological context and susceptibility against antimicrobial combinations.
      The isolate belongs to clonal complex 258 and harbors several acquired genes and
      mutations associated with antimicrobial resistance.

PMID- 29021087
TI  - Evaluation of OneStep Dengue NS1 RapiDipTM InstaTest and OneStep Dengue Fever
      IgG/IgM RapiCardTM InstaTest during the course of a dengue type 1 epidemic.
AB  - We determined the diagnostic performance of the OneStep NS1 and the OneStep
      IgG/IgM RDT kits against a panel of samples which comprised of 174 dengue
      positive and 165 dengue negative sera characterized by three reference enzyme
      linked immunosorbent assays (ELISAs). The diagnostic sensitivities of the OneStep
      kits for the detection of individual biomarkers of NS1, IgM and IgG were 90% (95%
      CI: 82.1-94.7), 32.4% (95% CI: 24.8-40.8) and 44.4% (95% CI: 38.2-50.7),
      respectively. The combination of the OneStep IgG/IgM kit with the OneStep NS1 kit
      demonstrated significantly higher sensitivities for the combined NS1/IgM (96.8%;
      95% CI: 90.9-99.3) and NS1/IgM/IgG (99.5%; 95% CI: 97.1-99.9)(P<0.001). In
      conclusion, the OneStep NS1 kit has high sensitivity and specificity and is
      highly recommended for use. The low sensitivities for IgG (44.4%) and for IgM
      (32.4%) of the OneStep IgG/IgM kit when used alone suggest it is best used in
      combination with the OneStep NS1 kit to enhance its overall diagnostic
      performance.

PMID- 29021088
TI  - The impact of strain-specific immunity on Lyme disease incidence is spatially
      heterogeneous.
AB  - Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common
      tick-borne infection in the US. Recent studies have demonstrated that the
      incidence of human Lyme disease would have been even greater were it not for the
      presence of strain-specific immunity, which protects previously infected patients
      against subsequent infections by the same B. burgdorferi strain. Here, spatial
      heterogeneity is incorporated into epidemiological models to accurately estimate
      the impact of strain-specific immunity on human Lyme disease incidence. The
      estimated reduction in the number of Lyme disease cases is greater in
      epidemiologic models that explicitly include the spatial distribution of Lyme
      disease cases reported at the county level than those that utilize nationwide
      data. strain-specific immunity has the greatest epidemiologic impact in
      geographic areas with the highest Lyme disease incidence due to the greater
      proportion of people that have been previously infected and have developed strain
      specific immunity.

PMID- 29021089
TI  - Patellofemoral arthritis treated with resurfacing implant: Clinical outcome and
      complications at a minimum two-year follow-up.
AB  - BACKGROUND: This study evaluated the clinical and radiographic outcomes of a
      series of patients treated with an anatomic inlay resurfacing implant, with a
      minimum two-year follow-up. METHODS: Fifteen patients underwent patellofemoral
      resurfacing procedures using a HemiCAP Wave Patellofemoral Inlay Resurfacing
      implant from 2010 to 2013. Clinical outcomes included: Visual Analog Scale (VAS),
      Lysholm score, Knee Society Score (KSS), and evaluation of Kujala, and Hospital
      for Special Surgery Patellofemoral score (HSS-PF). The postoperative
      complications were analyzed. RESULTS: Nineteen knees were evaluated; the average
      follow-up was 35.2months. Fourteen were women, with an average age of 54years.
      The pre-operative/postoperative clinical results presented a significant
      improvement: VAS 8/2.5, Lysholm 31.9/85.8, KSS 39.8/82.5, Kujala 32.1/79.3 and
      Hospital for Special Surgery Patellofemoral score (HSS-PF) 15.9/90.6. A total of
      87% of patients were either satisfied or very satisfied with the overall outcome.
      There were no radiographic signs of loosening. Seven postoperative complications
      were recorded: two presented ongoing knee pain, one postoperative stiffness, one
      patellar bounce due to maltracking, two ilio-tibial band syndrome, and one tibial
      anterior tuberosity osteotomy nonunion. Two patients underwent a total knee
      arthroplasty conversion and were considered a failure. None of these
      complications were implant related. CONCLUSIONS: Patellofemoral inlay resurfacing
      for isolated patellofemoral arthritis was an effective and safe procedure with
      high levels of patient satisfaction. No mechanical implant failure was seen at a
      minimum two-year follow-up. This implant design appeared to be an alternative to
      the traditional patellofemoral prostheses. Concomitant osteochondral lesions,
      patellofemoral dysplasia or patellar maltracking might be poor prognostic factors
      for this type of implant.

PMID- 29021090
TI  - RBBB tachycardia with north-west axis. What is the mechanism?
AB  - RBBB tachycardia with NW axis is considered to be VT unless proved otherwise.
      However underlying conduction system disease can produce electrocardiographic
      patterns suggestive of bundle branch block with extreme left axis which can cause
      difficulty in differentiating VT from SVT as in this case.

PMID- 29021092
TI  - T-cells and their cytokine production: The anti-inflammatory and
      immunosuppressive effects of strenuous exercise.
AB  - Strenuous exercise bouts and heavy training are associated with a heightened anti
      inflammatory state and a transient suppression of several immune components. In
      turn, many athletes are susceptible to illness, particularly upper respiratory
      symptoms (e.g. cough, sore throat, running nose). T-lymphocytes (T-cells) are
      important for orchestrating the immune response and can be categorised into
      subsets according to their phenotypical characteristics resulting from
      polarisation (i.e. type-1, type-2 and regulatory T-cells). Each T-cell subset has
      a unique functional role, including their capacity to produce pro- and anti
      inflammatory cytokines in response to an immune challenge. Prolonged and
      exhaustive exercise typically reduces peripheral blood type-1 T-cell number and
      their capacity to produce the pro-inflammatory cytokine, interferon-gamma.
      Moreover, heavy training loads are associated with elevated numbers of resting
      peripheral blood type-2 and regulatory T-cells, which characteristically produce
      the anti-inflammatory cytokines, interleukin-4 and interleukin-10, respectively.
      This appears to increase the risk of upper respiratory symptoms, potentially due
      to the cross-regulatory effect of interleukin-4 on interferon-gamma production
      and immunosuppressive action of IL-10. Catecholamines significantly influence the
      number of peripheral blood T-cells in response to exercise. Whereas,
      glucocorticoids and prostaglandin E2 promote the production of anti-inflammatory
      cytokines by T-cells. In summary, strenuous exercise bouts and heavy training
      shifts T-cell immunity towards an anti-inflammatory state. This impairs the
      ability of the immune system to mount an inflammatory response to an immune
      challenge, which may weaken defences against intracellular pathogens (e.g.
      viruses), and increase the risk of infection and viral reactivation.

PMID- 29021091
TI  - An evaluation of multiple algorithms for the measurement of the heart rate
      corrected JTpeak interval.
AB  - Interest in the effects of drugs on the heart rate-corrected JTpeak (JTpc)
      interval from the body-surface ECG has spawned an increasing number of scientific
      investigations in the field of regulatory sciences, and more specifically in the
      context of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. We
      conducted a novel initiative to evaluate the role of automatic JTpc measurement
      technologies by comparing their ability to distinguish multi- from single-channel
      blocking drugs. A set of 5232 ECGs was shared by the FDA (through the Telemetric
      and Holter ECG Warehouse) with 3 ECG device companies (AMPS, Mortara, and
      Philips). We evaluated the differences in drug-concentration effects on these
      measurements between the commercial and the FDA technologies. We provide a
      description of the drug-induced placebo-corrected changes from baseline for
      dofetilide, quinidine, ranolazine, and verapamil, and discuss the various
      differences across all technologies. The results revealed only small differences
      between measurement technologies evaluated in this study. It also confirms that,
      in this dataset, the JTpc interval distinguishes between multi- and single
      channel (hERG) blocking drugs when evaluating the effects of dofetilide,
      quinidine, ranolazine, and verapamil. However, in the case of quinidine and
      dofetilide, we noticed a poor consistency across technologies because of the lack
      of standard definitions for the location of the peak of the T-wave (T-apex) when
      the T-wave morphology is abnormal.

PMID- 29021093
TI  - Disseminated cryptococcosis in a patient taking tocilizumab for Castleman's
      disease.
AB  - Infections occur more frequently in patients receiving biologics. However,
      cryptococcal infection is uncommon in patients receiving tocilizumab, an
      interleukin-6 inhibitor, in contrast to patients receiving tumor necrosis factor
      alpha inhibitors. In this report, we describe a case of disseminated
      cryptococcosis in a 55-year-old man who was receiving tocilizumab every 2 weeks
      along with daily prednisolone and cyclosporine for Castleman's disease. He
      initially developed cellulitis on both upper limbs, and his condition worsened
      despite antibacterial therapy. Chest X-ray scanning and computed tomography
      demonstrated bilateral pulmonary infiltration. Cryptococcus neoformans was
      detected in blood, skin, and sputum cultures. He was diagnosed with disseminated
      cryptococcosis, and successfully treated with liposomal amphotericin B for a week
      followed by oral fluconazole for 11 months. The findings of this study indicate
      that cryptococcosis should be considered during the differential diagnosis of
      infection in patients receiving tocilizumab, especially in the presence of other
      risk factors for infections or a short tocilizumab dosing interval.

PMID- 29021094
TI  - Socio-demographic, lifestyle, and dietary determinants of essential and possibly
      essential trace element levels in adipose tissue from an adult cohort.
AB  - There is increasing evidence linking levels of trace elements (TEs) in adipose
      tissue with certain chronic conditions (e.g., diabetes or obesity). The
      objectives of this study were to assess concentrations of a selection of nine
      essential and possibly-essential TEs in adipose tissue samples from an adult
      cohort and to explore their socio-demographic, dietary, and lifestyle
      determinants. Adipose tissue samples were intraoperatively collected from 226
      volunteers recruited in two public hospitals from Granada province. Trace
      elements (Co, Cr, Cu, Fe, Mn, Mo, Se, V, and Zn) were analyzed in adipose tissue
      by high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). Data
      were collected on socio-demographic characteristics, lifestyle, diet, and health
      status by face-to-face interview. Predictors of TE concentrations were assessed
      by using multivariable linear and logistic regression. All TEs were detected in
      all samples with the exception of Se (53.50%). Iron, zinc, and copper showed the
      highest concentrations (42.60 mg/kg, 9.80 mg/kg, and 0.68 mg/kg, respectively).
      Diet was the main predictor of Cr, Fe, Mo, and Se concentrations. Body mass index
      was negatively associated with all TEs (beta coefficients = -0.018 to -0.593, p =
      0.001-0.090) except for Mn and V. Age showed a borderline-significant positive
      correlation with Cu (beta = 0.004, p = 0.089). Residence in a rural or semi-rural
      area was associated with increased Co, Cr, Fe, Mo, Mn, V and Zn concentrations
      and with beta coefficients ranging from 0.196 to 0.544 (p < 0.05). Furthermore,
      individuals with higher educational level showed increased Cr, Co, Fe and V
      concentrations (beta coefficients = 0.276-0.368, p = 0.022-0.071). This is the
      first report on the distribution of these TEs in adipose tissue and on their
      determinants in a human cohort and might serve as an initial step in the
      elucidation of their clinical relevance.

PMID- 29021095
TI  - The role of wind field induced flow velocities in destratification and hypoxia
      reduction at Meiling Bay of large shallow Lake Taihu, China.
AB  - : Wind induced flow velocity patterns and associated thermal destratification can
      drive to hypoxia reduction in large shallow lakes. The effects of wind induced
      hydrodynamic changes on destratification and hypoxia reduction were investigated
      at the Meiling bay (N 31 degrees  22' 56.4", E 120 degrees  9' 38.3") of Lake
      Taihu, China. Vertical flow velocity profile analysis showed surface flow
      velocities consistency with the wind field and lower flow velocity profiles were
      also consistent (but with delay response time) when the wind speed was higher
      than 6.2 m/s. Wind field and temperature found the control parameters for hypoxia
      reduction and for water quality conditions at the surface and bottom profiles of
      lake. The critical temperature for hypoxia reduction at the surface and the
      bottom profile was <=24.1C degrees  (below which hypoxic conditions were found
      reduced). Strong prevailing wind field (onshore wind directions ESE, SE, SSE and
      E, wind speed ranges of 2.4-9.1 m/s) reduced the temperature (22C degrees  to
      24.1C degrees ) caused reduction of hypoxia at the near surface with a rise in
      water levels whereas, low to medium prevailing wind field did not supported
      destratification which increased temperature resulting in increased hypoxia. Non
      prevailing wind directions (offshore) were not found supportive for the reduction
      of hypoxia in study area due to less variable wind field. Daytime wind field
      found more variable (as compared to night time) which increased the thermal
      destratification during daytime and found supportive for destratification and
      hypoxia reduction. The second order exponential correlation found between surface
      temperature and Chlorophyll-a (R2: 0.2858, Adjusted R-square: 0.2144 RMSE:
      4.395), Dissolved Oxygen (R2: 0.596, Adjusted R-square: 0.5942, RMSE: 0.3042)
      concentrations. The findings of the present study reveal the driving mechanism of
      wind induced thermal destratification and hypoxic conditions, which may further
      help to evaluate the wind role in eutrophication process and algal blooms
      formation in shallow water environments. OUTCOME: Wind field is the key control
      factor for thermal destratification and hypoxia reduction. 24.1C degrees  is the
      critical/threshold temperature for hypoxia, Chlorophyll-a and NH3-N
      concentrations of the shallow freshwater lake.

PMID- 29021096
TI  - Occurrence, sources and transport of antibiotics in the surface water of coral
      reef regions in the South China Sea: Potential risk to coral growth.
AB  - Laboratory research has indicated that antibiotics had negative effects on coral
      growth by disturbing natural microbiota; however, no field studies have reported
      antibiotic contamination levels and their influence on coral growth in natural
      coral reef regions (CRRs). This study investigated antibiotic occurrence and
      sources in the surface water from CRRs that have suffered from rapid coral
      degradation and evaluated their risk to coral growth. These regions are in the
      South China Sea, including four coastal and two offshore CRRs. The results show
      that 13 antibiotics were detected in the coastal CRRs with concentrations ranging
      from 10-2-100 ng L-1, while 5 antibiotics occurred in offshore CRRs (300-950 km
      from the mainland), with concentrations ranging from 10-2 to 10-1 ng L-1. Their
      concentrations decreased gradually from the coast to offshore in the transport
      process. However, Yongxing Island, which is approximately 300 km from the
      mainland, was an exception with relatively higher concentrations than the
      surrounding reefs because of the ever-increasing human activity on the island.
      The presence of anthropogenic contaminants antibiotics in CRRs may be a potential
      risk to coral growth.

PMID- 29021097
TI  - Durable superhydrophobic and superamphiphobic polymeric surfaces and their
      applications: A review.
AB  - Wetting control is essential for many applications, such as self-cleaning, anti
      icing, anti-fogging, antibacterial action as well as anti-reflection and friction
      control. While significant effort has been devoted to fabricate
      superhydrophobic/superamphiphobic surfaces (repellent to water and other low
      surface tension liquids), very few polymeric superhydrophobic/superamphiphobic
      surfaces can be considered as durable against various externally imposed stresses
      (e.g. application of heating, pressure, mechanical forces, chemical, etc.).
      Therefore, durability tests are extremely important for applications especially
      when such surfaces are made of "soft" materials. Here, we review the most recent
      and promising efforts reported towards the realization of durable,
      superhydrophobic/superamphiphobic, polymeric surfaces emphasizing the durability
      tests performed, and some important applications. We compare and put in context
      the scattered durability tests reported in the literature, and present
      conclusions, perspectives and challenges in the field.

PMID- 29021098
TI  - Discussion of: "The hypercoagulability paradox of chronic kidney disease: The
      role of fibrinogen".

PMID- 29021099
TI  - Discussion of: "Targeting resuscitation to normalization of coagulating status:
      Hyper and hypocoagulability after severe injury are both associated with
      increased mortality".

PMID- 29021100
TI  - The value of endomyocardial biopsy in diagnosis and guiding therapy.
AB  - Endomyocardial biopsy (EMB) is a highly-specialised procedure that is associated
      with some controversy as to its diagnostic role due to its inconsistency in
      diagnosing a wide variety of cardiac diseases. Given the advances and
      sophistication in echocardiography and cardiac magnetic resonance imaging (MRI),
      the vast majority of cardiac diseases can be diagnosed by these non-invasive
      procedures. Under-sampling and the fact that biopsy site is limited to the right
      side of the interventricular septum further limits its value. In spite of all
      these limitations, there still remains a group of pathological conditions that
      require biopsy for a conclusive diagnosis such as myocarditis, amyloidosis,
      sarcoidosis and giant cell myocarditis. Correct patient selection and the
      quantity of tissue samples impart a significant influence on the accuracy of the
      diagnosis, and thus the value of EMB is variable for each patient. The purpose of
      this study was to evaluate the role of EMB in patient care, through its ability
      to either change clinical diagnosis or alter patient management. Our study was
      based in a single teaching centre. An audit of cardiac biopsies performed over a
      10 year period identified 250 patients. We assessed indications, histology,
      electron microscopic findings, final clinical diagnosis and how they influenced
      patient management. A definite diagnosis on histology was given in 44 of 250
      patients (17.6%). Non-specific findings were observed in the remaining 206
      patients (82.4%). Histology influenced patient management in 73 (29.2%) patients.
      Histological examination in the remaining 177 biopsies (70.8%) did not provide a
      definite diagnosis or influence patient management. It was additionally found
      that the number of tissue fragments sampled has significant impact on diagnostic
      accuracy. A more accurate diagnosis of 45% was obtained when >=5 fragments were
      sampled, as compared to 1-3 fragments where accuracy dropped to 20%. Our study
      indicated that sampling for electron microscopy has very limited value. We found
      that of 245 biopsies sampled for electron microscopy, only three biopsies (1.2%)
      had diagnostically useful findings. In our institution procedure related
      complications were observed in 7 of 250 patients (2.8%). The diagnostic value of
      EMB is important but limited. Strict triaging of patients according to clinical
      suspicion and adequate sampling of tissue may increase useful diagnostic
      information.

PMID- 29021101
TI  - Comparison between the patients with surgery and without surgery after
      recommendation of surgical repair for symptomatic rotator cuff tear.
AB  - PURPOSE: Symptomatic full-thickness rotator cuff (RC) tears are often recommended
      for surgical repairs. However, some patients decide not to have surgery. The aim
      of this study was to see if there was any difference in preoperative variables
      between the two groups. METHODS: 137 consecutive patients recommended for surgery
      due to symptomatic full-thickness RC tear were evaluated. At mean 58.1 months
      after surgery-recommendation, the patients were asked whether they had surgery
      and their clinical outcome was assessed. Variables at the time of surgery
      recommendation including demographics, range-of-motion (ROM), tear size, and
      fatty infiltration on MRI, and clinical score were compared between the two
      groups. RESULTS: The 59 men and 78 women had a mean age of 64.4 years. Overall,
      104 (75.9%) patients were treated with RC repair and 33 (24.1%) were not. The
      main three reasons for not having surgery were improvement of symptoms or minimal
      pain (55%), economic burden (12%), and concern for postoperative long
      rehabilitation (9%). Demography and ROM measured at the time of surgery
      recommendation did not differ. All clinical scores at one year and final follow
      up survey showed no difference between the two groups. The Constant and UCLA
      scores at the time of surgery-recommendation were significantly higher and tear
      size was smaller in the 'No-surgery' group. Fatty infiltration of supraspinatus
      (2.0 versus 1.2, p < 0.001) and global fatty degeneration index (1.4 versus 0.8,
      p = 0.011) were statistically lower in 'No-surgery' group as well. CONCLUSION:
      Patients with relatively preserved function and small size tear tend to select
      non-surgical treatment and lead to relatively good outcome.

PMID- 29021102
TI  - Predictors of the clinical outcome and survival without degenerative arthritis
      after surgical treatment of femoroacetabular impingement.
AB  - BACKGROUND: The main purposes of the present study were to evaluate the
      functional improvement, to identify the predictors of the clinical outcome after
      open surgical management of femoroacetabular impingement (FAI) in mid-term, and
      to determine 5-year survival rate. METHODS: In this retrospective study, the
      clinical data of 33 patients (34 hips) were evaluated. Sex, age, body mass index
      (BMI), type of FAI, duration of symptoms up to surgical treatment, internal
      rotation of the affected hip, improvement of the Harris hip score (HHS) in the
      first 2 years, joint space narrowing evaluated radiographically and classified
      according to Kellgren-Lawrence classification, and any labral tear were the
      independent variables. Harris hip score and degenerative arthritic changes at the
      latest follow-up were identified as outcome measures. Univariate and multivariate
      analyses were performed. The mean post-operative follow-up was 6 years. RESULTS:
      Harris hip scores at the latest follow-up were significantly worse in patients
      with a pre-operative age >35 years, BMI >=25 kg/m2, internal rotation of the hip
      <=10 degrees , grade 1 or 2 joint space narrowing, labral tear, and <15 points
      improvement of the HHS at the first 2 years follow-up. According to multivariate
      analysis; major predictors of the outcome were BMI, labral tear, and improvement
      of the HHS at the first 2 years. CONCLUSIONS: A pre-operative BMI >=25 kg/m2,
      labral tear, and <20 points improvement of the HHS in the first 2 years of
      surgery should be considered as the major predictors of the clinical outcome
      after open surgical management of idiopathic FAI.

PMID- 29021103
TI  - Retrospective analysis of relapsed abdominal high-risk neuroblastoma.
AB  - BACKGROUND/PURPOSE: The impact of abdominal topography and surgical technique on
      resectability and local relapse pattern of relapsed abdominal high-risk
      neuroblastoma (R-HR-NB) is not clearly defined. METHODS: A sample of thirty-nine
      patients with R-HR-NB enrolled in the German neuroblastoma trials between 2001
      and 2010 was analyzed retrospectively using surgical and imaging reports. We
      evaluated resectability and local relapse pattern within 6 standardized abdominal
      regions, impact of extent of the first resective surgery on overall survival
      (OS), and of number of operations and a higher cumulative surgical assessment
      score (C-SAS) on OS after the first event. RESULTS: In the left upper abdomen,
      rates for tumor persistence and relapse were 45.9% and 13.5% and in the left
      lower abdomen 27.7% and 8.3%, respectively. OS in months did not differ between
      complete and incomplete first resections (median (interquartile range): 35 (45.6)
      vs. 40 (65.4), P=.649). Better OS after the first event was associated with
      repeated as compared to single surgery (47.7 (64.7) vs. 4.3 (12.5), P=.000), and
      with higher as compared to lower C-SAS (47.7 (64.3) vs. 7.6 (14.7), P=.002).
      CONCLUSIONS: OS after relapse/progression was not dependent on the extent of
      first resection. The number of operations was associated with better outcome
      after event. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: LEVEL III
      Retrospective comparative study.

PMID- 29021104
TI  - Did Liszt have chronic pulmonary thromboembolism?

PMID- 29021105
TI  - Invasive pneumococcal pneumonia caused by 13-valent pneumococcal conjugate
      vaccine types in children with different schedules.
AB  - BACKGROUND: In Taiwan, the age group with the greatest incidence of invasive
      pneumococcal disease is 2-5 years of age, which is different from other
      countries. This study was conducted to identify risk factors and different 13
      valent pneumococcal conjugate vaccine (PCV13) schedules associated with vaccine
      type invasive pneumococcal pneumonia (IPP) despite prior vaccination. METHODS: A
      case-control study was conducted prospectively between August 2012 and December
      2015 at five participating medical centers. The study enrolled children <15 years
      of age who were admitted to one of the five medical centers for CAP. Blood
      samples and acute-phase serum specimens were collected and Streptococcus
      pneumoniae was identified by using a real-time polymerase-chain-reaction (RT-PCR)
      assay targeting the lytA gene. RESULTS: A total of 25 children diagnosed with
      vaccine-type IPP and 124 controls were enrolled. Vaccine-type IPP occurred in 6
      (28.6%), 14 (24.1%), and 5 (7.1%) children receiving vaccines on a not-age
      appropriate schedule (n = 21), primary infant schedule (n = 58), and toddler
      catch-up schedule (n = 70) (P = 0.008), respectively. Of 25 children, the mean
      age at disease onset was 36 +/- 11 months; serotype 19A was responsible for 84%
      (21/25). CONCLUSION: After adjustment for confounding factors, the risk of
      vaccine-type IPP was significantly higher among children receiving vaccines on a
      not-age-appropriate schedule, or on a primary infant schedule, compared with
      children receiving vaccines on a toddler catch-up schedule. Duration of vaccine
      immunity should be investigated to direct strategies for maintaining individual
      and population immunity against pneumococcal disease.

PMID- 29021106
TI  - Use of on-site detoxification services co-located with a supervised injection
      facility.
AB  - OBJECTIVES: Supervised injection facilities (SIFs) are increasingly being
      implemented worldwide in response to the harms associated with injection drug
      use. Although SIFs have been shown to promote engagement of people who use
      injection drugs (PWID) with external health services, little is known about the
      potential of co-locating on-site detoxification services with SIFs. The aim of
      this study was to characterize use of detoxification services co-located at
      Insite, North America's first SIF, among PWID in Vancouver, Canada. METHODS: Data
      were derived from two prospective cohorts of PWID in Vancouver, Canada between
      November 2010 and December 2012. Using multivariable generalized estimating
      equation logistic regression, we identified factors independently associated with
      reporting use of detoxification services at the SIF. RESULTS: Among 1316 PWID,
      147 (11.2%) reported enrolling in detoxification services co-located with the SIF
      at least once during the two year study period. In multivariable analyses, after
      adjustment for other potential cofounders, factors independently and positively
      associated with use of this service included residence<5 blocks from the SIF
      (Adjusted Odds Ratio [AOR]=1.70), enrollment in methadone maintenance therapy
      (AOR=1.90), public injection (AOR=1.53), binge injection (AOR=1.93), recent
      overdose (AOR=1.90) and frequent SIF use (AOR=8.15) (all p<0.05). DISCUSSION: Use
      of on-site detoxification services offered at the SIF was common among PWID and
      associated with frequent SIF use and various markers of vulnerability and drug
      related risk. These findings highlight the potential role of SIFs as a point of
      access to detoxification services for high-risk PWID. Future studies should
      examine if co-location leads to higher uptake of addiction services in comparison
      to services that create geographic or other obstacles.

PMID- 29021107
TI  - Marijuana use and HIV treatment outcomes among PWH receiving care at an urban HIV
      clinic.
AB  - BACKGROUND: While marijuana use is prevalent among persons with HIV (PWH), few
      studies have examined the relationship between marijuana use and HIV treatment
      outcomes independent of alcohol and other drug use. METHODS: We conducted a
      prospective cohort study to examine the relationships between frequency of
      marijuana use and antiretroviral therapy (ART) adherence and viral suppression in
      patients enrolled in the Johns Hopkins HIV Clinical Cohort between September 2013
      through November 2015 (N=1377). We categorized marijuana use as no use, none in
      the last 3months, monthly use or less, weekly/daily. Our outcomes of interest
      were use of ART, >=90 ART adherence, and viral suppression (HIV1-RNA<200 copies).
      We conducted multivariable analyses to examine associations between the frequency
      of marijuana use and our treatment outcomes, using generalized estimating
      equations to account for repeated measures. Other independent variables of
      interest included alcohol use, other drug use, and depressive symptoms. Analyses
      were adjusted for age, race, sex and HIV acquisition risk factor. RESULTS: In
      multivariable analyses we found no statistically significant association between
      frequency of marijuana use and our treatment outcomes. Alcohol use, other drug
      use and depressive symptoms were associated with lower odds of ART adherence and
      viral suppression. CONCLUSIONS: In this sample of PWH in care, frequency of
      marijuana use independent of other substance use does not appear to be associated
      with negative HIV treatment outcomes. Our results indicate that unlike alcohol,
      other substances and depression, marijuana use may not be a barrier to the
      effective treatment of HIV.

PMID- 29021108
TI  - Effects of a multifaceted implementation intervention to increase utilization of
      pharmacological treatments for alcohol use disorders in the US Veterans Health
      Administration.
AB  - Over 16 million Americans meet diagnostic criteria for alcohol use disorder
      (AUD), but only 7.8% of them receive formal treatment each year. Safe and
      effective pharmacological treatments for AUD exist; however, they are rarely
      prescribed. Therefore, we developed and pilot tested a multifaceted
      implementation intervention to improve consideration and receipt of effective
      pharmacologic treatments for AUD, focusing on primary care settings where
      patients have the most frequent contact with healthcare systems. The intervention
      included training of local providers to serve as champions and a website for
      primary care providers that included educational materials, a case-finding
      dashboard, and contact information for local and national clinical experts. We
      also mailed patients educational material about treatment options. The
      intervention was implemented at three large facilities of the Veterans Health
      Administration (VHA). An interrupted time series design, analyzed with segmented
      logistic regression, was used to evaluate the intervention's effects. The odds of
      a patient with AUD receiving one of the AUD medications was increasing throughout
      the pre-implementation period, and the rate of change (slope) increased
      significantly in the implementation period. Translating these numbers into
      percentages, at baseline 2.9% of patients filled a prescription for an AUD
      medication within 30days of a primary care visit. This increased to 3.8% by the
      end of the pre-implementation period (increasing 0.037% per month), and increased
      to 5.2% by the end of the implementation period (increasing 0.142% per month).
      However, the intervention effect was not significant when control sites were
      added, suggesting that improvement may have been driven by secular trends rather
      than solely by this intervention. Although the intervention was feasible, it was
      not effective. Continued analysis of process and implementation data including
      qualitative interviews with key stakeholders, may elucidate the reasons this
      intervention was not successful and ways to strengthen its effects.

PMID- 29021109
TI  - Design and impact of bundled payment for detox and follow-up care.
AB  - INTRODUCTION: Recent payment reforms promote movement from fee-for-service to
      alternative payment models that shift financial risk from payers to providers,
      incentivizing providers to manage patients' utilization. Bundled payment, an
      episode-based fixed payment that includes the prices of a group of services that
      would typically treat an episode of care, is expanding in the United States.
      Bundled payment has been recommended as a way to pay for comprehensive SUD
      treatment and has the potential to improve treatment engagement after detox,
      which could reduce detox readmissions, improve health outcomes, and reduce
      medical care costs. However, if moving to bundled payment creates large losses
      for some providers, it may not be sustainable. The objective of this study was to
      design the first bundled payment for detox and follow-up care and to estimate its
      impact on provider revenues. METHODS: Massachusetts Medicaid beneficiaries'
      behavioral health, medical, and pharmacy claims from July 2010-April 2013 were
      used to build and test a detox bundled payment for continuously enrolled adults
      (N=5521). A risk adjustment model was developed using general linear modeling to
      predict beneficiaries' episode costs. The projected payments to each provider
      from the risk adjustment analysis were compared to the observed baseline costs to
      determine the potential impact of a detox bundled payment reform on
      organizational revenues. This was modeled in two ways: first assuming no change
      in behavior and then assuming a supply-side cost sharing behavioral response of a
      10% reduction in detox readmissions and an increase of one individual counseling
      and one group counseling session. RESULTS: The mean total 90-day detox episode
      cost was $3743. Nearly 70% of the total mean cost consists of the index detox,
      psychiatric inpatient care, and short-term residential care. Risk mitigation,
      including risk adjustment, substantially reduced the variation of the mean
      episode cost. There are opportunities for organizations to gain revenue under
      this bundled payment design, but many providers will lose money under a bundled
      payment designed using historic payment and costs. CONCLUSIONS: Designing a
      bundled payment for detox and follow-up care is feasible, but low case volume and
      the adequacy of the payment are concerns. Thus, a detox episode-based payment
      will likely be more challenging for smaller, independent SUD treatment providers.
      These providers are experiencing many changes as financing shifts away from block
      grant funding toward Medicaid funding. A detox bundled payment in practice would
      need to consider different risk mitigation strategies, provider pooling, and
      costs based on episodes of care meeting quality standards, but could incentivize
      care coordination, which is important to reducing detox readmissions and engaging
      patients in care.

PMID- 29021111
TI  - Exploring mortality among drug treatment clients: The relationship between
      treatment type and mortality.
AB  - AIMS: Studies consistently identify substance treatment populations as more
      likely to die prematurely compared with age-matched general population, with
      mortality risk higher out-of-treatment than in-treatment. While opioid-using
      pharmacotherapy cohorts have been studied extensively, less evidence exists
      regarding effects of other treatment types, and clients in treatment for other
      drugs. This paper examines mortality during and following treatment across
      treatment modalities. METHODS: A retrospective seven-year cohort was utilised to
      examine mortality during and in the two years following treatment among clients
      from Victoria, Australia, recorded on the Alcohol and Drug Information Service
      database by linking with National Death Index. 18,686 clients over a 12-month
      period were included. Crude (CMRs) and standardised mortality rates (SMRs) were
      analysed in terms of treatment modality, and time in or out of treatment.
      RESULTS: Higher risk of premature death was associated with residential
      withdrawal as the last type of treatment engagement, while mortality following
      counselling was significantly lower than all other treatment types in the year
      post-treatment. Both CMRs and SMRs were significantly higher in-treatment than
      post-treatment. CONCLUSION: Better understanding of factors contributing to
      elevated mortality risk for clients engaged in, and following treatment, is
      needed to ensure that treatment systems provide optimal outcomes during and after
      treatment.

PMID- 29021112
TI  - American counselors' acceptance of non-abstinence outcome goals for clients
      diagnosed with co-occurring substance use and other psychiatric disorders.
AB  - Previous research has examined clinicians' acceptance of non-abstinence for
      clients who have a substance use disorder (SUD), but many SUD clients also
      present with a psychiatric disorder. To evaluate the acceptability of non
      abstinence as a final outcome goal for clients with co-occurring diagnoses, we
      recruited a nationwide sample of 751 American substance abuse counselors to
      complete a web-based questionnaire. Respondents rated the acceptability of
      limited/moderate consumption by clients diagnosed with each of 18 co-occurring
      disorders: three psychiatric disorders (Major Depressive Disorder, Post-Traumatic
      Stress Disorder, Social Phobia) x three substances (alcohol, cannabis, opioids) x
      two levels of severity (DSM-5 Moderate SUD, DSM-5 Severe SUD). On average, non
      abstinence was rated as unacceptable for clients with any of the 18 diagnostic
      pairs, although one-fourth to almost one-third rated limited/moderate use of
      cannabis somewhat or completely acceptable for clients diagnosed with a Moderate
      Cannabis Use Disorder when paired with any of the three psychiatric disorders.
      Furthermore, small proportions of respondents (13% to 20%) rated non-abstinence
      at least somewhat acceptable even when clients were diagnosed with a Severe SUD
      for any of the three substances and any co-occurring psychiatric disorder. Based
      on our findings, clients with co-occurring disorders who want to moderate their
      substance use will typically find their counselor does not accept that outcome
      goal. Because supporting non-abstinence respects client autonomy, could attract
      and retain clients in counseling, and is consistent with a recovery-oriented
      treatment model, we encourage continuing education about the benefits of non
      abstinence as a treatment goal for clients with co-occurring disorders.

PMID- 29021114
TI  - A police-led addiction treatment referral program in Gloucester, MA:
      Implementation and participants' experiences.
AB  - BACKGROUND: The increasing rates of opioid use disorder and resulting overdose
      deaths are a public health emergency, yet only a fraction of individuals in need
      receive treatment. OBJECTIVE: To describe the implementation of and participants'
      experiences with a novel police-led addiction treatment referral program.
      METHODS: Follow-up telephone calls to participants in the Gloucester Police
      Department's Angel Program from June 2015-May 2016. Open-ended survey
      questionnaires assessed experiences of program participants and their close
      contacts, confirmed police-reported placement, and queried self-reported
      substance use and treatment outcomes. RESULTS: Surveys were completed by 198 of
      367 individuals (54% response rate) who participated 214 times. Reasons for
      participation included: the program was a highly-visible entry point to the
      treatment system, belief that placement would be obtained, poor prior treatment
      system experiences, and external pressure to seek treatment. Most participants
      reported positive experiences citing the welcoming, non-judgmental services. In
      75% (160/214) of the encounters, entry into referral placement was confirmed.
      Participants expressed frustration when they did not meet program entry
      requirements and had difficulty finding sustained treatment following initial
      program placement. At a mean follow-up time of 6.7months, 37% of participants
      reported abstinence since participation, with no differences between participants
      who entered referral placement versus those who did not. CONCLUSIONS: A police
      led referral program was feasible to implement and acceptable to participants.
      The program was effective in finding initial access to treatment, primarily
      through short-term detoxification services. However, the program was not able to
      overcome a fragmented treatment system focused on acute episodic care which
      remains a barrier to long-term recovery.

PMID- 29021113
TI  - Association between alcohol consumption and injection and sexual risk behaviors
      among people who inject drugs in rural Puerto Rico.
AB  - Although alcohol use has been associated with risky behavior generally, the
      relationship between alcohol use and multiple types of risk behaviors that could
      lead to the acquisition and transmission of HIV and hepatitis C (HCV) among
      people who inject drugs (PWID) has not been fully examined. The current study
      seeks to contribute to the understanding of how alcohol use is related to both
      injection risk and sexual risk, among a non-treatment, cross-sectional sample of
      mostly male PWID in rural Puerto Rico (n=315). "At-risk" alcohol use was defined
      as consuming >=14 drinks per week for males and >=7 drinks per week for females.
      Binge drinking frequency was defined as consuming >=5 drinks on one occasion for
      males and >=4 drinks on a single occasion for females. Multivariate regression
      models were used to examine the association between the alcohol use variables and
      injection and sexual risk outcomes, adjusting for demographic characteristics.
      Overall, 14% (n=45) of the participants in this sample were considered at-risk
      drinkers (44% low risk drinkers and 42% alcohol abstainers), and participants
      reported binge drinking, on average, at least once per month. At-risk drinking,
      compared to low risk or no drinking, increased both injection and sexual risk
      behaviors. Frequency of past year binge drinking was also associated with both
      injection and sexual risk behaviors. Interventions aimed at reducing HIV and HCV
      transmission among injection drug users non-PWID networks should both target
      individuals who drink alcohol frequently and in high volumes, and include
      strategies for reducing risky behaviors while heavy drinking is occurring.

PMID- 29021110
TI  - Collaborative care from the emergency department for injured patients with
      prescription drug misuse: An open feasibility study.
AB  - Collaborative Care is a comprehensive longitudinal care management strategy. The
      purpose of this pilot effectiveness-implementation hybrid study was to determine
      the feasibility of a Collaborative Care intervention initiated from the Emergency
      Department and proceeding longitudinally for six months for injured patients with
      prescription drug misuse (PDM). Adult patients presenting to an urban ED with an
      injury were screened for eligibility from 2/2015-8/2015. Eligible participants
      with a positive screen for PDM were enrolled in the 'ED-LINC' intervention which
      included the following elements: 1) active care coordination and linkage, 2)
      medication safety and utilization of opioid guidelines 3) longitudinal care
      management and 4) utilization of Electronic Medical Record (EMR) innovations such
      as the statewide Emergency Department Information Exchange (EDIE) and statewide
      prescription monitoring program information for assessment and follow-up.
      Baseline characteristics of the sample were assessed and regression models were
      used to evaluate longitudinal trajectories of risk for PDM. A total of 36
      participants (56% of patients approached) had PDM and 30 participants were
      enrolled. Of those enrolled, 37% had prescription stimulant misuse, 20% with
      prescription sedative misuse and 97% had prescription opioid misuse. Follow-up
      rates at all time points were >=83%. Baseline levels of comorbidity were high;
      57% endorsed recent heroin use and 70% endorsed symptoms consistent with major
      depression. Over 50% had five or more statewide ED visits and 53% had used three
      or more different ED's in the past year. On average, participants received a
      total of 85 minutes of ED-LINC over six months with 90% of participants receiving
      all four intervention elements. All patients had care coordinated with new or
      existing primary care providers (PCP's) and 23% were linked to a new PCP. A
      majority of patients (>=80%) reported receiving high quality, desired
      intervention services. There was no significant change in PDM over time.
      Collaborative Care initiated from the ED is feasible and acceptable to patients
      with trauma and PDM. Future directions could include effectiveness-implementation
      hybrid trials to study implementation barriers and strategies as well as patient
      level outcomes of this intervention for this complex patient population.

PMID- 29021116
TI  - Efficacy of a technology-based, integrated smoking cessation and alcohol
      intervention for smoking cessation in adolescents: Results of a cluster
      randomised controlled trial.
AB  - OBJECTIVE: To test the efficacy of a technology-based integrated smoking
      cessation and alcohol intervention versus a smoking cessation only intervention
      in adolescents. METHODS: This was a two-arm, parallel-group, cluster-randomised
      controlled trial with assessments at baseline and six months follow-up. Subjects
      in both groups received tailored mobile phone text messages to support smoking
      cessation for 3months, and the option of registering for a program incorporating
      strategies for smoking cessation centred around a self-defined quit date.
      Subjects in the integrated intervention group also received tailored feedback
      regarding their consumption of alcohol and, for binge drinkers, tailored mobile
      phone text messages encouraging them to maintain their drinking within low-risk
      limits over a 3-month period. Primary outcome measures were the 7-day point
      prevalence of smoking abstinence and change in cigarette consumption. RESULTS: In
      360 Swiss vocational and upper secondary school classes, 2127 students who smoked
      tobacco regularly and owned a mobile phone were invited to participate in the
      study. Of these, 1471 (69.2%) participated and 6-month follow-up data were
      obtained for 1116 (75.9%). No significant group differences were observed for any
      of the primary or secondary outcomes. Moderator analyses revealed beneficial
      intervention effects concerning 7-day smoking abstinence in participants with
      higher versus lower alcohol consumption. CONCLUSIONS: Overall, the integrated
      smoking cessation and alcohol intervention exhibited no advantages over a smoking
      cessation only intervention, but it might be more effective for the subgroup of
      adolescent smokers with higher alcohol consumption. Providing a combined smoking
      cessation and alcohol intervention might be recommended for adolescent smokers
      with higher-level alcohol consumption.

PMID- 29021115
TI  - Specialty addiction and psychiatry treatment initiation and engagement: Results
      from an SBIRT randomized trial in pediatrics.
AB  - OBJECTIVE: Many adolescents needing specialty addiction or psychiatry treatment
      never access care. We examined initiation and engagement with addiction and/or
      psychiatry treatment among adolescents referred to treatment from a trial
      comparing two different modalities of delivering Screening, Brief Intervention
      and Referral to Treatment (SBIRT) to Usual Care in pediatric primary care. We
      hypothesized that both intervention arms would have higher initiation and
      engagement rates than usual care. METHODS: We randomized all pediatricians (n=52)
      in a pediatric primary care clinic to three arms: 1) pediatrician-only arm, in
      which pediatricians were trained to deliver SBIRT for substance use and/or mental
      health problems; 2) embedded-behavioral health clinician (embedded-BHC arm), in
      which pediatricians referred adolescents who endorsed substance use and/or mental
      health problems to a BHC; and 3) Usual Care (UC). We used electronic health
      record (EHR) data to examine specialty addiction and psychiatry treatment
      initiation and engagement rates after referral. RESULTS: Among patients who
      screened positive for substance use and/or mental health problems and were
      referred to specialty addiction and/or psychiatry (n=333), those in the embedded
      BHC arm had almost four times higher odds of initiating treatment than those in
      the pediatrician-only arm, OR=3.99, 95% CI=[1.99-8.00]. Compared to UC, those in
      the pediatrician-only arm had lower odds of treatment initiation (OR=0.53, 95%
      CI=[0.28-0.99]), while patients in the embedded-BHC arm had marginally higher
      odds (OR=1.83, 95% CI=[0.99-3.38]). Black patients and those with other/unknown
      race/ethnicity had lower odds of treatment initiation compared with white
      adolescents; there were no gender or age differences. We found no differences in
      treatment engagement across the three arms. CONCLUSIONS: Embedded BHCs can have a
      significant positive impact on facilitating treatment initiation for pediatric
      primary care adolescents referred to addiction and/or psychiatry services.
      CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov #NCT02408952.

PMID- 29021117
TI  - There is an app for that - Or is there? A content analysis of publicly available
      smartphone apps for managing alcohol use.
AB  - INTRODUCTION: Smartphone apps are emerging as a promising tool to support
      recovery from and prevention of problematic alcohol use, yet it is unclear what
      type of apps are currently available in the public domain, and to what degree
      these apps use interactive tailoring or other dynamic features to meet users'
      specific needs. METHODS: We conducted a content analysis of Android apps for
      managing drinking available on Google Play (n=266), downloaded between November
      21, 2014 and June 25, 2015. We recorded app popularity (>10,000 downloads) and
      user-rated quality (number of stars) from Google Play, and coded the apps on
      three domains (basic descriptors, functionality, use of dynamic features).
      RESULTS: In total, the reviewed 266 apps were downloaded at least 2,793,567 times
      altogether. The most common types of app were BAC calculators (37%), information
      provision apps (37%), tracking calendars (24%), and motivational tools (21%).
      Most apps were free (65%) or low in cost (mean=$3.76; SD=$5.80). Many apps
      provided at least some level of tailored feedback (60%), but the extent of
      tailoring was limited. Use of other dynamic features (i.e., push notifications,
      passive data collection) was largely absent. Univariate models predicting app
      popularity (i.e., >10,000 downloads vs. not) and user-rated quality (i.e., star
      rating) indicated that tailoring was positively related to popularity (OR=2.41
      [1.30-4.46]), and the existence of time-based tailoring (e.g., tracking) was
      related to quality (b=0.48 [0.19-0.77]). CONCLUSIONS: These apps have a wide
      public health reach with >2.7 million total combined downloads to date. A wide
      variety of apps exist, allowing persons interested in using apps to help them
      manage their drinking to choose from numerous types of supports. Tailoring, while
      related favorably to an app's popularity and user-rated quality, is limited in
      publicly available apps.

PMID- 29021118
TI  - Convergence of online daily diaries and timeline followback among women at risk
      for alcohol exposed pregnancy.
AB  - Researchers and clinicians interested in assessing drinking and unprotected sex
      in evaluating risk for alcohol-exposed pregnancy (AEP) have limited options. The
      current investigation examined the degree to which data collected from online
      prospectively collected daily diaries (Diaries) converged with data from
      interviewer-administered retrospective timeline follow back (TLFB), the standard
      in AEP intervention studies. 71 women (Mage=27.7, SD=6.2) at risk for AEP were
      recruited via online advertising and were randomly assigned to an online patient
      education condition or a tailored, online internet intervention to reduce AEP
      risk. All participants were administered both Diaries and TLFB at baseline and
      6months after intervention. Key outcomes were variables of drinking rates and
      unprotected sex that combined to indicate risk for AEP. Zero-order and intra
      class correlations (ICC) between Diaries and TLFB were strong for each outcome.
      Examination of ICC confidence intervals indicated that condition assignment did
      not have a significant impact on the degree of convergence between Diaries and
      TLFB. With the exception of proportion of days drinking and proportion of days
      with unprotected sex at baseline, none of the paired t-tests reached
      significance. Examination of descriptive statistics revealed that 63% of
      participants reported problem alcohol use and unprotected sex in both the 10-day
      Diaries and 90-day TLFB at baseline, with 70% agreement at post 6-month follow
      up. Findings indicate overall strong agreement between TLFB and Diaries in
      detecting alcohol use and unprotected sex in women at risk for AEP, and each
      method has benefits and challenges that should be weighed carefully by
      researchers and treatment providers.

PMID- 29021120
TI  - Characteristics of pregnant women who reported alcohol use at admission to
      substance use treatment.
AB  - OBJECTIVES: The current study analyzed the sociodemographic, treatment-related,
      and other substance use characteristics among pregnant women who reported alcohol
      use and were admitted to substance use treatment for the first time. METHODS: The
      Treatment Episode Data Set-Admission (TEDS-A) between 1992 and 2012 was used for
      conducting a cross-sectional study. RESULTS: Among pregnant women admitted to
      substance use treatment for the first time (N=166,863), 43.1% reported alcohol
      use of whom half used alcohol as the primary drug of choice. The proportion of
      pregnant women reporting any alcohol use declined over the study period, while
      the proportions of subgroups within pregnant women reporting alcohol use remained
      stable within the population. Those reporting alcohol use only notably had the
      highest proportion of women aged 40 or older and non-Hispanic White who were more
      educated, employed, and married, compared to those reporting alcohol use as
      primary but also other substance use and those reporting other substance as
      primary drug of choice. Those reporting only alcohol also were more likely to be
      referred by the justice system to outpatient treatment. Marijuana was the most
      popular co-used substance among pregnant women who use alcohol as primary drug of
      choice in the dataset. CONCLUSIONS: Differences in sociodemographic, treatment
      related, and other substance use characteristics between the three subgroups may
      help inform public health interventions aimed at mitigating the effects of
      prenatal alcohol use on maternal and child health.

PMID- 29021119
TI  - A pilot randomized trial of Motivational Interviewing compared to Psycho
      Education for reducing and preventing underage drinking in American Indian
      adolescents.
AB  - Underage drinking is an important public health issue for American Indian and
      Alaska Native (AI/AN) adolescents, as it is for U. S. teens of all ethnicities.
      One of the demonstrated risk factors for the development of alcohol use disorders
      in AI/AN is early age of initiation of drinking. To address this issue a
      randomized trial to assess the efficacy of Motivational Interviewing (MI)
      compared to Psycho-Education (PE) to reduce and prevent underage drinking in
      AI/AN youth was developed and implemented. Sixty-nine youth received MI or PE and
      87% were assessed at follow-up. For teens who were already drinking,
      participating in the intervention (MI or PE) was associated, at follow-up, with
      lower quantity*frequency (q*f) of drinking (p=0.011), fewer maximum drinks per
      drinking occasion (p=0.004), and fewer problem behaviors (p=0.009). The MI
      intervention resulted in male drinkers reporting a lower q*f of drinking
      (p=0.048) and female drinkers reporting less depression (p=0.011). In teens who
      had not started drinking prior to the intervention, 17% had initiated drinking at
      follow-up. As a group they reported increased quantity*frequency of drinking
      (p=0.008) and maximum drinks (p=0.047), but no change in problem behaviors. These
      results suggest that intervening against underage drinking using either MI or PE
      in AI/AN youth can result in reduced drinking, prevention of initiation of
      drinking, and other positive behavioral outcomes. Brief interventions that
      enhance motivation to change as well as Psycho-Education may provide a successful
      approach to reducing the potential morbidity of underage drinking in this high
      risk group.

PMID- 29021121
TI  - Effect of computerized cognitive behavioral therapy on acquisition of coping
      skills among cocaine-dependent individuals enrolled in methadone maintenance.
AB  - : The acquisition of coping skills has long been considered one of the putative
      mechanisms of cognitive behavioral therapy (CBT) for substance use disorders, yet
      consistent statistical support is lacking. This study sought to replicate and
      extend prior findings regarding the quality of coping skills as a mediator of
      abstinence outcomes from a computerized CBT program for substance users.
      Participants were methadone-maintained, cocaine dependent individuals enrolled in
      a clinical trial evaluating the efficacy of computer-based training for CBT
      ('CBT4CBT') as an add-on to treatment as usual (TAU+CBT4CBT) compared to TAU
      only. A subsample (N=71) completed a role play assessment to measure coping
      skills, the Drug Risk Response Test (DRRT), which was administered before, during
      (week 4), and after the 8-week treatment period. Participants' verbal responses
      to various high-risk situations for cocaine use were recorded and independent
      evaluators rated the quality of the coping responses. Results of repeated
      measures analyses revealed a main effect of time for the quality of overall
      responses [F(1, 141.26)=4.29, p<0.01], indicating improvement in the quality of
      coping skills across groups, yet no differential effect of treatment. Despite the
      significant association between coping responses and abstinence outcomes,
      analyses did not support the quality of coping skills as a mediator of treatment
      effects. However, among the high-risk situations wherein individuals provided
      lower quality responses at baseline, those assigned to TAU+CBT4CBT showed greater
      improvement compared to those assigned to TAU only [F(1, 697.65)=6.47, p=0.01].
      CONCLUSIONS: This study failed to replicate the quality of coping skills as a
      mediator of CBT4CBT's effect on reducing drug use previously shown in a mixed
      outpatient substance use sample. However, in this methadone maintained sample,
      those with poorer quality skills in response to certain high-risk situations at
      baseline appeared to improve their coping strategies following CBT4CBT compared
      to standard methadone treatment alone.

PMID- 29021122
TI  - Influencing quality of outpatient SUD care: Implementation of alerts and
      incentives in Washington State.
AB  - Financial incentives for quality improvement and feedback on specific clients are
      two approaches to improving the quality of treatment for individuals with
      substance use disorders. We examined the impacts of these interventions in
      Washington State by randomizing outpatient substance use treatment agencies into
      intervention and control groups. From October 2013 through December 2015,
      agencies could earn financial incentives for meeting performance goals
      incorporating both achievement relative to a benchmark and improvement from
      agencies' own baselines. Weekly feedback was e-mailed to agencies in the alert or
      alert plus incentives arms. Difference-in difference regressions controlling for
      client and agency characteristics showed that none of the interventions
      significantly affected client engagement after outpatient admissions, overall or
      for sub-groups based on race/ethnicity, age, rural residence, or agency baseline
      performance. Treatment agencies offered insights related to several themes:
      delivery system context (e.g., agency time and resources needed during transition
      to a managed behavioral healthcare system), implementation (e.g., data lag),
      agency issues (e.g., staff turnover), and client factors (e.g., motivation).
      Interventions took place during a time of Medicaid expansion and planning for
      statewide integration of mental health and substance use disorder treatment into
      a managed care model, which may have resulted in agencies not responding to the
      interventions. Moreover, incentives and alerts at the agency-level may not be
      effective when factors are at play beyond the agency's control.

PMID- 29021124
TI  - Finally, what we have been waiting for: evidence that transfusion of RBCs at the
      extreme of the storage spectrum is safe.

PMID- 29021123
TI  - Red blood cell storage and in-hospital mortality: a secondary analysis of the
      INFORM randomised controlled trial.
AB  - BACKGROUND: No randomised trials have addressed whether exposure to red blood
      cells (RBCs) stored longer than 35 days is associated with harm in patients. We
      aimed to assess the risk of in-hospital mortality associated with transfusing
      blood stored longer than 35 days. METHODS: We did a secondary analysis of the
      INforming Fresh versus Old Red cell Management (INFORM) trial, a pragmatic,
      multicentre, randomised controlled trial of patients (>=18 years) admitted to one
      of six hospitals in Australia, Canada, Israel, and the USA and expected to need
      RBC transfusions. Patients were randomly assigned (2:1) to receive blood in
      inventory stored for the longest time (standard care) or the shortest time, using
      a random allocation schedule and stratified by centre and patient ABO blood
      group. The primary objective of the INFORM trial was to assess all-cause in
      hospital mortality in patients with blood group A and O who were transfused. For
      our exploratory secondary analysis, we classified individuals into one of three
      mutually exclusive exposure categories on the basis of the maximum storage
      duration of any blood unit patients had received on each day in hospital:
      exclusively exposed to RBCs stored no longer than 7 days, exposed to at least one
      unit of RBCs stored 8-35 days, and exposed to least one unit of RBCs stored
      longer than 35 days. Our primary objective was to determine the effect on risk of
      in-hospital death of time-dependent exposure to RBCs stored longer than 35 days
      compared with exclusive exposure to RBCs stored no longer than 7 days, both in
      patients of blood groups A and O and all patients. The INFORM trial is registered
      as an International Standard Randomised Controlled Trial, number ISRCTN08118744.
      FINDINGS: Between April 2, 2012, and Oct 21, 2015, 31 497 patients were
      recruited, and 24 736 patients were eligible for inclusion in this analysis. We
      excluded nine patients for whom information about the storage duration of
      transfused blood was missing and one patient whose sex was unknown. 4480 (18%)
      patients were exposed to RBCs with longest storage, 1392 (6%) patients were
      exposed exclusively to RBCs with shortest storage, and 18 854 (76%) patients were
      exposed to RBCs stored 8-35 days. Median follow-up was 11 days (IQR 6-20).
      Exposure to RBCs stored longer than 35 days was not associated with increased
      risk of in-hospital death compared with exclusive exposure to the freshest RBC
      units after adjusting for demographic variables, diagnosis category, and blood
      product use history (in patients with blood group A or O: hazard ratio 0.94, 95%
      CI 0.73-1.20, p=0.60; in all patients: 0.91, 0.72-1.14, p=0.40). The risk of in
      hospital death also did not differ between patients exposed to blood stored 8-35
      days and patients exposed to blood stored 7 days or less (in patients with blood
      group A or O: 0.92, 0.74-1.15, p=0.48; in all patients: 0.90, 0.73-1.10, p=0.29).
      INTERPRETATION: These data provide evidence that transfusion of blood stored for
      longer than 35 days has no effect on in-hospital mortality, which suggests that
      current approaches to blood storage and inventory management are reasonable.
      FUNDING: Canadian Institutes for Health Research, Canadian Blood Services, and
      Health Canada.

PMID- 29021125
TI  - Characteristics of Innovators Adopting a National Personal Health Record in
      Portugal: Cross-Sectional Study.
AB  - BACKGROUND: Personal health records (PHRs) are increasingly being deployed
      worldwide, but their rates of adoption by patients vary widely across countries
      and health systems. Five main categories of adopters are usually considered when
      evaluating the diffusion of innovations: innovators, early adopters, early
      majority, late majority, and laggards. OBJECTIVE: We aimed to evaluate adoption
      of the Portuguese PHR 3 months after its release, as well as characterize the
      individuals who registered and used the system during that period (the
      innovators). METHODS: We conducted a cross-sectional study. Users and nonusers
      were defined based on their input, or not, of health-related information into the
      PHR. Users of the PHR were compared with nonusers regarding demographic and
      clinical variables. Users were further characterized according to their intensity
      of information input: single input (one single piece of health-related
      information recorded) and multiple inputs. Multivariate logistic regression was
      used to model the probability of being in the multiple inputs group. ArcGis
      (ESRI, Redlands, CA, USA) was used to create maps of the proportion of PHR
      registrations by region and district. RESULTS: The number of registered
      individuals was 109,619 (66,408/109,619, 60.58% women; mean age: 44.7 years,
      standard deviation [SD] 18.1 years). The highest proportion of registrations was
      observed for those aged between 30 and 39 years (25,810/109,619, 23.55%).
      Furthermore, 16.88% (18,504/109,619) of registered individuals were considered
      users and 83.12% (91,115/109,619) nonusers. Among PHR users, 32.18% (5955/18,504)
      engaged in single input and 67.82% (12,549/18,504) in multiple inputs. Younger
      individuals and male users had higher odds of engaging in multiple inputs (odds
      ratio for male individuals 1.32, CI 1.19-1.48). Geographic analysis revealed
      higher proportions of PHR adoption in urban centers when compared with rural
      noncoastal districts. CONCLUSIONS: Approximately 1% of the country's population
      registered during the first 3 months of the Portuguese PHR. Registered
      individuals were more frequently female aged between 30 and 39 years. There is
      evidence of a geographic gap in the adoption of the Portuguese PHR, with higher
      proportions of adopters in urban centers than in rural noncoastal districts.

PMID- 29021127
TI  - Fall Detection in Individuals With Lower Limb Amputations Using Mobile Phones:
      Machine Learning Enhances Robustness for Real-World Applications.
AB  - BACKGROUND: Automatically detecting falls with mobile phones provides an
      opportunity for rapid response to injuries and better knowledge of what
      precipitated the fall and its consequences. This is beneficial for populations
      that are prone to falling, such as people with lower limb amputations. Prior
      studies have focused on fall detection in able-bodied individuals using data from
      a laboratory setting. Such approaches may provide a limited ability to detect
      falls in amputees and in real-world scenarios. OBJECTIVE: The aim was to develop
      a classifier that uses data from able-bodied individuals to detect falls in
      individuals with a lower limb amputation, while they freely carry the mobile
      phone in different locations and during free-living. METHODS: We obtained 861
      simulated indoor and outdoor falls from 10 young control (non-amputee)
      individuals and 6 individuals with a lower limb amputation. In addition, we
      recorded a broad database of activities of daily living, including data from
      three participants' free-living routines. Sensor readings (accelerometer and
      gyroscope) from a mobile phone were recorded as participants freely carried it in
      three common locations-on the waist, in a pocket, and in the hand. A set of 40
      features were computed from the sensors data and four classifiers were trained
      and combined through stacking to detect falls. We compared the performance of two
      population-specific models, trained and tested on either able-bodied or amputee
      participants, with that of a model trained on able-bodied participants and tested
      on amputees. A simple threshold-based classifier was used to benchmark our
      machine-learning classifier. RESULTS: The accuracy of fall detection in amputees
      for a model trained on control individuals (sensitivity: mean 0.989,
      1.96*standard error of the mean [SEM] 0.017; specificity: mean 0.968, SEM 0.025)
      was not statistically different (P=.69) from that of a model trained on the
      amputee population (sensitivity: mean 0.984, SEM 0.016; specificity: mean 0.965,
      SEM 0.022). Detection of falls in control individuals yielded similar results
      (sensitivity: mean 0.979, SEM 0.022; specificity: mean 0.991, SEM 0.012). A mean
      2.2 (SD 1.7) false alarms per day were obtained when evaluating the model (vs
      mean 122.1, SD 166.1 based on thresholds) on data recorded as participants
      carried the phone during their daily routine for two or more days. Machine
      learning classifiers outperformed the threshold-based one (P<.001). CONCLUSIONS:
      A mobile phone-based fall detection model can use data from non-amputee
      individuals to detect falls in individuals walking with a prosthesis. We
      successfully detected falls when the mobile phone was carried across multiple
      locations and without a predetermined orientation. Furthermore, the number of
      false alarms yielded by the model over a longer period of time was reasonably
      low. This moves the application of mobile phone-based fall detection systems
      closer to a real-world use case scenario.

PMID- 29021126
TI  - HealthyDads.ca: What Do Men Want in a Website Designed to Promote Emotional
      Wellness and Healthy Behaviors During the Transition to Parenthood?
AB  - BACKGROUND: Up to 18% of men experience depression and/or anxiety during the
      transition to parenthood. Interventions designed specifically to promote the
      mental health of men during the transition to parenthood are scarce. Internet
      delivered interventions may be acceptable and far-reaching in enhancing mental
      health, parenting knowledge, and healthy behaviors in expectant or new fathers.
      OBJECTIVE: To guide the development of Healthydads.ca, a website designed to
      enhance mental health and healthy behaviors in expectant fathers, a needs
      assessment was conducted to identify fathers' perspectives of barriers to seeking
      help for emotional wellness, informational needs, and factors affecting the
      decision to visit such a website. METHODS: One hundred and seventy-four men whose
      partners were expecting, or had recently given birth, in 3 Canadian provinces
      (Quebec, Ontario, and Alberta) completed a Web-based survey inquiring about
      information needs related to psychosocial aspects of the transition to
      parenthood, lifestyle behaviors, parenting, and factors associated with the
      decision to visit a father-focused website. RESULTS: Most men (155/174, 89.1%)
      reported accessing the Internet to obtain information on pregnancy and spent an
      average of 6.2 hours online per month. Seeking information about parenting on the
      Internet was reported by 67.2% (117/174) of men, with a mean of 4.4 hours per
      month of online searching. Top barriers to seeking help to improve emotional
      wellness during the perinatal period were: no time to seek help/assistance
      (130/174, 74.7%), lack of resources available in the health care system (126/174,
      72.4%), financial costs associated with services (118/174, 67.8%), and feeling
      that one should be able to do it alone (113/174, 64.9%). Information needs that
      were rated highly included: parenting/infant care (52.9-81.6%), supporting
      (121/174, 69.5%) and improving (124/174, 71.3%) relationship with their partner,
      work-family balance (120/174, 69.0%), improving sleep (100/174, 57.5%), and
      managing stress (98/174, 56.3%). Perceiving the website as personally relevant
      (151/174, 86.8%), credible (141/174, 81.0%), effective (140/145, 80.5%), and
      having an easy navigation structure (141/174, 81.0%) were identified as important
      factors related to a first website visit. Providing useful (134/174, 77.0%) and
      easy to understand (158/174, 90.8%) information, which was also free of charge
      (156/174, 89.7%), were considered important for deciding to prolong a website
      visit. Providing the possibility to post questions to a health professional
      (133/174, 76.4%), adding new content regularly (119/174, 68.4%), and personal
      motivation (111/174, 63.8%) were factors identified that would encourage a
      revisit. CONCLUSIONS: Our findings demonstrate that there is substantial interest
      among expectant and new fathers for using Internet-delivered strategies to
      prepare for the transition to parenthood and support their mental health.
      Specific user and website features were identified to optimize the use of father
      focused websites.

PMID- 29021129
TI  - Real-World Treatment Sequences and Outcomes Among Patients With Non-Small Cell
      Lung Cancer (RESOUNDS) in the United States: Study Protocol.
AB  - BACKGROUND: Survival outcomes are related to treatment choices in a line of
      therapy and to treatment sequences across all lines of therapy. OBJECTIVE: The
      Real-World Treatment Sequences and Outcomes among Patients with NSCLC (RESOUNDS)
      study is designed to (1) evaluate treatment sequences used for patients who
      receive at least two lines of therapy for non-small cell lung cancer (NSCLC) in
      the United States and (2) evaluate patient outcomes in terms of progression-free
      and overall survival related to treatment sequencing. Additional objectives
      include the evaluation of symptoms, comorbidities, and health care resource
      utilization and costs. METHODS: Patients will be censored at loss to follow-up
      due to leaving the health plan or reaching the end of the study period. RESULTS:
      This study is ongoing. CONCLUSIONS: The RESOUNDS cohort study is a novel approach
      to building a comprehensive dataset that mimics a prospective observational study
      using linked patient-level data from four real-world data sources. This study
      will provide timely information on the sequencing of treatments for patients with
      NSCLC.

PMID- 29021128
TI  - Psychometric Properties of Patient-Facing eHealth Evaluation Measures: Systematic
      Review and Analysis.
AB  - BACKGROUND: Significant resources are being invested into eHealth technology to
      improve health care. Few resources have focused on evaluating the impact of use
      on patient outcomes A standardized set of metrics used across health systems and
      research will enable aggregation of data to inform improved implementation,
      clinical practice, and ultimately health outcomes associated with use of patient
      facing eHealth technologies. OBJECTIVE: The objective of this project was to
      conduct a systematic review to (1) identify existing instruments for eHealth
      research and implementation evaluation from the patient's point of view, (2)
      characterize measurement components, and (3) assess psychometrics. METHODS:
      Concepts from existing models and published studies of technology use and
      adoption were identified and used to inform a search strategy. Search terms were
      broadly categorized as platforms (eg, email), measurement (eg, survey),
      function/information use (eg, self-management), health care occupations (eg,
      nurse), and eHealth/telemedicine (eg, mHealth). A computerized database search
      was conducted through June 2014. Included articles (1) described development of
      an instrument, or (2) used an instrument that could be traced back to its
      original publication, or (3) modified an instrument, and (4) with full text in
      English language, and (5) focused on the patient perspective on technology,
      including patient preferences and satisfaction, engagement with technology,
      usability, competency and fluency with technology, computer literacy, and trust
      in and acceptance of technology. The review was limited to instruments that
      reported at least one psychometric property. Excluded were investigator-developed
      measures, disease-specific assessments delivered via technology or telephone (eg,
      a cancer-coping measure delivered via computer survey), and measures focused
      primarily on clinician use (eg, the electronic health record). RESULTS: The
      search strategy yielded 47,320 articles. Following elimination of duplicates and
      non-English language publications (n=14,550) and books (n=27), another 31,647
      articles were excluded through review of titles. Following a review of the
      abstracts of the remaining 1096 articles, 68 were retained for full-text review.
      Of these, 16 described an instrument and six used an instrument; one instrument
      was drawn from the GEM database, resulting in 23 articles for inclusion. None
      included a complete psychometric evaluation. The most frequently assessed
      property was internal consistency (21/23, 91%). Testing for aspects of validity
      ranged from 48% (11/23) to 78% (18/23). Approximately half (13/23, 57%) reported
      how to score the instrument. Only six (26%) assessed the readability of the
      instrument for end users, although all the measures rely on self-report.
      CONCLUSIONS: Although most measures identified in this review were published
      after the year 2000, rapidly changing technology makes instrument development
      challenging. Platform-agnostic measures need to be developed that focus on
      concepts important for use of any type of eHealth innovation. At present, there
      are important gaps in the availability of psychometrically sound measures to
      evaluate eHealth technologies.

PMID- 29021130
TI  - Knowledge Management Framework for Emerging Infectious Diseases Preparedness and
      Response: Design and Development of Public Health Document Ontology.
AB  - BACKGROUND: There are increasing concerns about our preparedness and timely
      coordinated response across the globe to cope with emerging infectious diseases
      (EIDs). This poses practical challenges that require exploiting novel knowledge
      management approaches effectively. OBJECTIVE: This work aims to develop an
      ontology-driven knowledge management framework that addresses the existing
      challenges in sharing and reusing public health knowledge. METHODS: We propose a
      systems engineering-inspired ontology-driven knowledge management approach. It
      decomposes public health knowledge into concepts and relations and organizes the
      elements of knowledge based on the teleological functions. Both knowledge and
      semantic rules are stored in an ontology and retrieved to answer queries
      regarding EID preparedness and response. RESULTS: A hybrid concept extraction was
      implemented in this work. The quality of the ontology was evaluated using the
      formal evaluation method Ontology Quality Evaluation Framework. CONCLUSIONS: Our
      approach is a potentially effective methodology for managing public health
      knowledge. Accuracy and comprehensiveness of the ontology can be improved as more
      knowledge is stored. In the future, a survey will be conducted to collect queries
      from public health practitioners. The reasoning capacity of the ontology will be
      evaluated using the queries and hypothetical outbreaks. We suggest the importance
      of developing a knowledge sharing standard like the Gene Ontology for the public
      health domain.

PMID- 29021133
TI  - Five minutes with . . . Nicola Strickland.

PMID- 29021132
TI  - Willingness to Use Mobile Phone Apps for HIV Prevention Among Men Who Have Sex
      with Men in London: Web-Based Survey.
AB  - BACKGROUND: Many men who have sex with men (MSM) use apps to connect with and
      meet other MSM. Given that these apps are often used to arrange sexual
      encounters, it is possible that apps may be suitable venues for messages and
      initiatives related to HIV prevention such as those to increase HIV testing rates
      among this population. OBJECTIVE: The purpose of this study was to assess
      willingness to use a new app for reminders of when to be tested for HIV infection
      among a sample of MSM in London who use apps to arrange sexual encounters.
      METHODS: Broadcast advertisements targeted users of a popular social-networking
      app for MSM in London. Advertisements directed users to a Web-based survey of
      sexual behaviors and sexual health needs. Willingness to use apps for reminders
      of when to be tested for HIV was assessed. In addition, participants responded to
      items assessing recent sexual behaviors, substance use, and demographic
      characteristics. Exploratory analyses were undertaken to examine differences in
      willingness to use an app by demographic and behavioral characteristics. RESULTS:
      Broadcast advertisements yielded a sample of 169 HIV-negative MSM. Overall, two
      thirds (108/169, 63.9%) reported willingness to use an app to remind them when to
      be tested for HIV. There were no significant differences in willingness to use
      these apps based on demographic characteristics, but MSM who reported recent
      binge drinking and recent club drug use more frequently reported willingness to
      use this app compared to their nonusing counterparts. CONCLUSIONS: MSM in this
      sample are willing to use a new app for HIV testing reminders. Given the high
      levels of willingness to use them, these types of apps should be developed,
      evaluated, and made available for this population.

PMID- 29021131
TI  - Participatory Disease Surveillance: Engaging Communities Directly in Reporting,
      Monitoring, and Responding to Health Threats.
AB  - BACKGROUND: Since 2012, the International Workshop on Participatory Surveillance
      (IWOPS) has served as an informal network to share best practices, consult on
      analytic methods, and catalyze innovation to advance the burgeoning method of
      direct engagement of populations in voluntary monitoring of disease. OBJECTIVE:
      This landscape provides an overview of participatory disease surveillance systems
      in the IWOPS network and orients readers to this growing field of practice.
      METHODS: Authors reviewed participatory approaches that include human and animal
      health surveillance, both syndromic (self- reported symptoms) and event-based,
      and how these tools have been leveraged for disease modeling and forecasting. The
      authors also discuss benefits, challenges, and future directions for
      participatory disease surveillance. RESULTS: There are at least 23 distinct
      participatory surveillance tools or programs represented in the IWOPS network
      across 18 countries. Organizations supporting these tools are diverse in nature.
      CONCLUSIONS: Participatory disease surveillance is a promising method to
      complement both traditional, facility-based surveillance and newer digital
      epidemiology systems.

PMID- 29021134
TI  - NIH Funds Pediatric Data Resource Center.
AB  - Children's Hospital of Philadelphia will lead a collaborative effort-funded with
      $14.8 million from the NIH-to pool genomic and phenotypic data from tens of
      thousands of patients to study the causes of pediatric cancer and structural
      birth defects.

PMID- 29021135
TI  - Histone Acetyltransferase KAT6A Upregulates PI3K/AKT Signaling through TRIM24
      Binding.
AB  - Lysine acetyltransferase KAT6A is a chromatin regulator that contributes to
      histone modification and cancer, but the basis of its actions are not well
      understood. Here, we identify a KAT6A signaling pathway that facilitates
      glioblastoma (GBM), where it is upregulated. KAT6A expression was associated with
      GBM patient survival. KAT6A silencing suppressed cell proliferation, cell
      migration, colony formation, and tumor development in an orthotopic mouse
      xenograft model system. Mechanistic investigations demonstrated that KAT6A
      acetylates lysine 23 of histone H3 (H3K23), which recruits the nuclear receptor
      binding protein TRIM24 to activate PIK3CA transcription, thereby enhancing
      PI3K/AKT signaling and tumorigenesis. Overexpressing activated AKT or PIK3CA
      rescued the growth inhibition due to KAT6A silencing. Conversely, the pan-PI3K
      inhibitor LY294002 abrogated the growth-promoting effect of KAT6A. Overexpression
      of KAT6A or TRIM24, but not KAT6A acetyltransferase activity-deficient mutants or
      TRIM24 mutants lacking H3K23ac-binding sites, promoted PIK3CA expression, AKT
      phosphorylation, and cell proliferation. Taken together, our results define an
      essential role of KAT6A in glioma formation, rationalizing its candidacy as a
      therapeutic target for GBM treatment. Cancer Res; 77(22); 6190-201. (c)2017 AACR.

PMID- 29021136
TI  - Distinct Angiogenic Changes during Carcinogenesis Defined by Novel Label-Free
      Dark-Field Imaging in a Hamster Cheek Pouch Model.
AB  - There remain gaps in knowledge concerning how vascular morphology evolves during
      carcinogenesis. In this study, we imaged neovascularization by label-free dark
      field microscopy of a 7,12-Dimethylbenz[a]anthracene (DMBA)-induced hamster cheek
      pouch model of oral squamous cell carcinoma (SCC). Wavelength-dependent imaging
      revealed distinct vascular features at different imaging depths and vessel sizes.
      Vascular tortuosity increased significantly in high-risk lesions, whereas
      diameter decreased significantly in hyperplastic and SCC lesions. Large vessels
      preserved the same trends seen in the original images, whereas small vessels
      displayed different trends, with length and diameter increasing during
      carcinogenesis. On the basis of these data, we developed and validated a
      classification algorithm incorporating vascular features from different vessel
      masks. Receiver operator curves generated from the classification results
      demonstrated high accuracies in discriminating normal and hyperplasia from high
      grade lesions (AUC > 0.94). Overall, these results provided automated imaging of
      vasculature in the earliest stages of carcinogenesis from which one can extract
      robust endpoints. The optical toolbox described here is simple, low-cost and
      portable, and can be used in a variety of health care and research settings for
      cancer prevention and pharmacology research. Cancer Res; 77(24); 7109-19. (c)2017
      AACR.

PMID- 29021137
TI  - DDB2 Is a Novel Regulator of Wnt Signaling in Colon Cancer.
AB  - Deregulation of the Wnt/beta-catenin signaling pathway drives the development of
      colorectal cancer, but understanding of this pathway remains incomplete. Here, we
      report that the damage-specific DNA-binding protein DDB2 is critical for beta
      catenin-mediated activation of RNF43, which restricts Wnt signaling by removing
      Wnt receptors from the cell surface. Reduced expression of DDB2 and RNF43 was
      observed in human hyperplastic colonic foci. DDB2 recruited EZH2 and beta-catenin
      at an upstream site in the Rnf43 gene, enabling functional interaction with
      distant TCF4/beta-catenin-binding sites in the intron of Rnf43 This novel
      activity of DDB2 was required for RNF43 function as a negative feedback regulator
      of Wnt signaling. Mice genetically deficient in DDB2 exhibited increased
      susceptibility to colon tumor development in a manner associated with higher
      abundance of the Wnt receptor-expressing cells and greater activation of the
      downstream Wnt pathway. Our results identify DDB2 as both a partner and regulator
      of Wnt signaling, with an important role in suppressing colon cancer development.
      Cancer Res; 77(23); 6562-75. (c)2017 AACR.

PMID- 29021140
TI  - Fulminant Bacillus cereus septicaemia with multiple organ ischaemic/haemorrhagic
      complications in a patient undergoing chemotherapy for acute myelogenous
      leukaemia.
AB  - Bacillus cereus is a Gram-positive spore-forming rod widely found in the
      environment and is thought to be a frequent source of contamination. This micro
      organism is reportedly a significant pathogenic agent among immunocompromised
      individuals. Furthermore, multiple cases of fulminant septicaemia have been
      reported among individuals receiving chemotherapy for acute myelogenous
      leukaemia. In some cases, B. cereus septicaemia was associated with multiple
      haemorrhages. We, herein, describe a patient with an extremely acute course of B.
      cereus septicaemia characterised by haemorrhage and infarction of multiple
      organs, which led to his death. Our findings suggest that delayed treatment of B.
      cereus in patients with haematologic malignancies undergoing chemotherapy may
      result in extremely poor outcomes; thus, immediate empirical treatment with
      vancomycin should be considered.

PMID- 29021139
TI  - Paxillin Binding to the Cytoplasmic Domain of CD103 Promotes Cell Adhesion and
      Effector Functions for CD8+ Resident Memory T Cells in Tumors.
AB  - CD8+/CD103+ tissue-resident memory T cells (TRM cells) accumulate in several
      human solid tumors, where they have been associated with a favorable prognosis.
      However, the role of CD103, the alpha subunit of the integrin alphaEbeta7 (also
      known as CD103), in the retention and functions of these TRM is undefined. In
      this report, we investigated the role of CD103 cytoplasmic domain and the focal
      adhesion-associated protein paxillin (Pxn) in downstream signaling and functional
      activities triggered through alphaE/CD103 chain. Binding to immobilized
      recombinant (r)E-cadherin-Fc of CD103 integrin expressed on tumor-specific CTL
      clones promotes phosphorylation of Pxn and Pyk2 and binding of Pxn to the
      alphaE/CD103 subunit tail. Inhibition of Pxn phosphorylation by the Src inhibitor
      saracatinib or its knockdown via shRNA dramatically altered adhesion and
      spreading of freshly isolated CD8+/CD103+ lung tumor-infiltrating lymphocytes and
      CD103+ tumor-specific CTL clones. Inhibition of Pxn phosphorylation with
      saracatinib in these CTL clones also severely compromised their functional
      activities toward autologous tumor cells. Using Jurkat T cells as a model to
      study CD103 integrin activation, we demonstrated a key role of serine residue
      S1163 of the alphaE chain intracellular domain in polarization of CD103 and
      recruitment of lysosomes and Pxn at the contact zone of T lymphocytes with rE
      cadherin-Fc-coated beads. Overall, our results show how Pxn binding to the CD103
      cytoplasmic tail triggers alphaEbeta7 integrin outside-in signaling that promotes
      CD8+ T-cell migratory behavior and effector functions. These results also explain
      the more favorable prognosis associated with retention of TRM cells in the tumor
      microenvironment. Cancer Res; 77(24); 7072-82. (c)2017 AACR.

PMID- 29021138
TI  - Glutamine Addiction in Kidney Cancer Suppresses Oxidative Stress and Can Be
      Exploited for Real-Time Imaging.
AB  - Many cancers appear to activate intrinsic antioxidant systems as a means to
      counteract oxidative stress. Some cancers, such as clear cell renal cell
      carcinoma (ccRCC), require exogenous glutamine for growth and exhibit
      reprogrammed glutamine metabolism, at least in part due to the glutathione
      pathway, an efficient cellular buffering system that counteracts reactive oxygen
      species and other oxidants. We show here that ccRCC xenograft tumors under the
      renal capsule exhibit enhanced oxidative stress compared with adjacent normal
      tissue and the contralateral kidney. Upon glutaminase inhibition with CB-839 or
      BPTES, the RCC cell lines SN12PM-6-1 (SN12) and 786-O exhibited decreased
      survival and pronounced apoptosis associated with a decreased GSH/GSSG ratio,
      augmented nuclear factor erythroid-related factor 2, and increased 8-oxo-7,8
      dihydro-2'-deoxyguanosine, a marker of DNA damage. SN12 tumor xenografts showed
      decreased growth when treated with CB-839. Furthermore, PET imaging confirmed
      that ccRCC tumors exhibited increased tumoral uptake of 18F-(2S,4R)4
      fluoroglutamine compared with the kidney in the orthotopic mouse model. This
      technique can be utilized to follow changes in ccRCC metabolism in vivo Further
      development of these paradigms will lead to new treatment options with
      glutaminase inhibitors and the utility of PET to identify and manage patients
      with ccRCC who are likely to respond to glutaminase inhibitors in the clinic.
      Cancer Res; 77(23); 6746-58. (c)2017 AACR.

PMID- 29021141
TI  - Use of a dynamic gait trainer for a child with thoracic level spinal cord injury.
AB  - Paediatric spinal cord injury (SCI) can result in permanent mobility impairment
      with consequences for activity, participation and quality of life. This case
      documents the effect of an overground supported stepping intervention using a
      dynamic gait trainer. To our knowledge, there are no published studies on this
      intervention for children with SCI and similar interventions have only been
      reported in children at American Spinal Injury Association Impairment Scale (AIS)
      levels B and C.A child with a T10 (thoracic level, vertebra 10), AIS level A
      injury, sustained at 2 years of age, continued to make gains in all areas
      including participation, activity, body structure and function over the following
      4 years. Use of a dynamic gait trainer improved the participant's ability to be
      active and participate despite lack of further neuromuscular recovery. This novel
      approach with a commonly available device allowed the child to be active and
      participate in the absence of neural recovery.

PMID- 29021142
TI  - Knotted urethral catheter: an unusual complication in adults.
AB  - Knotting of feeding tubes or urinary catheters has been reported as a rare
      complication in paediatrics when draining the bladder. This is caused by
      inserting thin flexible tubes too far in, allowing it to coil. We present a case
      of a 70-year-old woman who was catheterised during a routine spinal surgery, and
      the catheter coiled and balloon failed to deflate requiring a cystostopic
      approach to puncture the balloon and remove it. Awareness of this complication in
      female catheterisation and education on length of catheter insertion is important
      to avoid this.

PMID- 29021143
TI  - Cold agglutinins in a patient undergoing normothermic cardiac operation with warm
      cardioplegia.
AB  - Cold agglutinins are autoantibodies that agglutinate red blood cells at low
      temperatures, leading to haemagglutination and haemolysis. They are generally of
      no clinical significance. However, when people with cold agglutinins undergo
      cardiac operation with hypothermia and cold cardioplegia, they can experience
      complications. Thus, different perioperative management is required for such
      patients. We describe a 74-year-old man with cold agglutinins incidentally
      detected on the preoperative screening test. He had never experienced any
      complications or developed a haematological disease. Since cold agglutinins were
      incidentally detected on the preoperative test, a special strategy was used to
      manage the temperature of cardiopulmonary bypass (CPB) and cardioplegia. He
      successfully underwent normothermic cardiac operation with warm cardioplegia. A
      continuous retrograde hyperkalaemic infusion and intermittent antegrade infusion
      of warm cardioplegia with normothermic CPB is one of the best methods to avoid
      hypothermia and excessive activity and metabolism of the heart, and to provide a
      suitable operative field.

PMID- 29021144
TI  - Metastatic primary seminal vesicle adenocarcinoma: management of a rare tumour
      with multiagent chemotherapy and hormonal therapy.
AB  - Primary seminal vesicle adenocarcinoma is one of the rarest genitourinary
      cancers. The pathogenesis is unknown and clinical manifestations are protean.
      There is no defined treatment for this disease and various combinations of
      surgery, chemotherapy, radiation therapy and hormonal therapy have been used in
      the past. Here, we have reported a primary seminal vesicle adenocarcinoma with
      hepatic metastases, managed with multiagent chemotherapy (oxaliplatin and 5
      fluorouracil based) and androgen ablation (with triptorelin). The key to
      management of such a case is early diagnosis and multimodal treatment. The
      reported survival rate continues to be poor even for a localised disease. A
      consolidated follow-up protocol ensures early diagnosis of recurrent or
      metastatic disease so that second-line therapy can be started.

PMID- 29021145
TI  - Early sonographic detection of a succenturiate placenta after IVF in a 42-year
      old woman with multiple comorbidities.
AB  - We present a case of a 42-year-old woman with a pregnancy resulting from in vitro
      fertilisation and a medical history including two spontaneous abortions,
      hypercoagulable state and other comorbidities. At 13 4/7 weeks' gestation, during
      research ultrasonography, the patient was noted to have an anterior succenturiate
      placental lobe. Following an episode of vaginal bleeding at 21 6/7 weeks, she was
      diagnosed with a low-lying posterior placental lobe. Velamentous cord insertion,
      placenta previa and vasa previa were excluded at that time. After elective
      induction for advanced maternal age at 39 0/7 weeks, arrest of labour and
      chorioamnionitis resulted in a primary low transverse caesarean section and
      delivery of a healthy girl at 39 3/7 weeks. Gross examination of the placenta
      showed an irregular, singleton placenta with an attached succenturiate lobe and a
      marginally inserting umbilical cord. Both lobes were connected by two vessels.

PMID- 29021146
TI  - Double PCL sign on sagittal MRI of the knee.

PMID- 29021147
TI  - Atypical haematological presentation in a case of polycythaemia vera with a new
      variant mutation detected in exon 12: c.1605G>T (p.Met535Ile).
AB  - One of the major genetic insights into the pathogenesis of polycythaemia vera
      included the identification of the somatic point gain-of-function mutations in
      Janus kinase 2 gene-first JAK2V617F on exon 14, present in 95%-97% of the cases,
      and later on exon 12. In the literature, we can find some reported studies where
      different exon 12 mutations are identified. Unlike patients with JAK2V617F
      mutation in exon 14, the mutation at exon 12 is not usually associated with an
      increase in the three haematopoietic series (erythrocytosis, leucocytosis and
      thrombocytosis). It appears to be associated with a distinct syndrome, mostly
      characterised by isolated and more marked erythrocytosis, independently of the
      mutational variant. We report here the case of a patient who is JAK2exon 12
      positive, presenting a novel mutation-c.1605G>T (p.Met535Ile)-associated with
      c.1612C>T (p.His538Tyr) mutation previously described, evidencing an atypical
      clinical phenotype.

PMID- 29021148
TI  - The voltage sensor of excitation-contraction coupling in mammals: Inactivation
      and interaction with Ca2.
AB  - In skeletal muscle, the four-helix voltage-sensing modules (VSMs) of CaV1.1
      calcium channels simultaneously gate two Ca2+ pathways: the CaV1.1 pore itself
      and the RyR1 calcium release channel in the sarcoplasmic reticulum. Here, to gain
      insight into the mechanism by which VSMs gate RyR1, we quantify intramembrane
      charge movement associated with VSM activation (sensing current) and gated Ca2+
      release flux in single muscle cells of mice and rats. As found for most four
      helix VSMs, upon sustained depolarization, rodent VSMs lose the ability to
      activate Ca2+ release channels opening; their properties change from a
      functionally capable mode, in which the mobile sensor charge is called charge 1,
      to an inactivated mode, charge 2, with a voltage dependence shifted toward more
      negative voltages. We find that charge 2 is promoted and Ca2+ release inactivated
      when resting, well-polarized muscle cells are exposed to low extracellular [Ca2+]
      and that the opposite occurs in high [Ca2+]. It follows that murine VSMs are
      partly inactivated at rest, which establishes the reduced availability of voltage
      sensing as a pathogenic mechanism in disorders of calcemia. We additionally find
      that the degree of resting inactivation is significantly different in two mouse
      strains, which underscores the variability of voltage sensor properties and their
      vulnerability to environmental conditions. Our studies reveal that the resting
      and activated states of VSMs are equally favored by extracellular Ca2+ Promotion
      by an extracellular species of two states of the VSM that differ in the
      conformation of the activation gate requires the existence of a second gate,
      inactivation, topologically extracellular and therefore accessible from outside
      regardless of the activation state.

PMID- 29021149
TI  - The envenomation of general physiology throughout the last century.
AB  - Toxins are the poisonous products of organisms. Toxins serve vital defensive and
      offensive functions for those that harbor them: stinging scorpions, pesticidal
      plants, sanguinary snakes, fearless frogs, sliming snails, noxious newts, and
      smarting spiders. For physiologists, toxins are integral chemical tools that
      hijack life's fundamental processes with remarkable molecular specificity. Our
      understanding of electrophysiological phenomena has been transformed time and
      time again with the help of some terrifying toxins. For this reason, studies of
      toxin mechanism are an important and enduring facet of The Journal of General
      Physiology (JGP). This Milestone in Physiology reflects on toxins studied in JGP
      over its first 100 years, what they have taught us, and what they have yet to
      reveal.

PMID- 29021151
TI  - Rapid Nanopore Sequencing of Plasmids and Resistance Gene Detection in Clinical
      Isolates.
AB  - Recent advances in nanopore sequencing technology have led to a substantial
      increase in throughput and sequence quality. Together, these improvements may
      permit real-time benchtop genomic sequencing and antimicrobial resistance gene
      detection in clinical isolates. In this study, we evaluated workflows and
      turnaround times for a benchtop long-read sequencing approach in the clinical
      microbiology laboratory using the Oxford Nanopore Technologies MinION sequencer.
      We performed genomic and plasmid sequencing of three clinical isolates with both
      MinION and Illumina MiSeq, using different library preparation methods (2D and
      rapid 1D) with the goal of antimicrobial resistance gene detection. We
      specifically evaluated the advantages of using plasmid DNA for sequencing and the
      value of supplementing MinION sequences with MiSeq reads for increasing assembly
      accuracy. Resequencing of three plasmids in a reference Klebsiella pneumoniae
      isolate demonstrated ~99% accuracy of draft MinION-only assembly and >99.9%
      accuracy of assembly polished with MiSeq reads. Plasmid DNA sequencing of
      previously uncharacterized clinical extended-spectrum beta-lactamase (ESBL)
      producing Escherichia coli and K. pneumoniae isolates using MinION allowed
      successful identification of antimicrobial resistance genes in the draft assembly
      corresponding to all classes of observed plasmid-based phenotypic resistance.
      Importantly, use of plasmid DNA enabled lower depth sequencing, and assemblies
      sufficient for full antimicrobial resistance gene annotation were obtained with
      as few as 2,000 to 5,000 reads, which could be acquired in 20 min of sequencing.
      With a MinION-only workflow that balances accuracy against turnaround time, full
      annotation of plasmid resistance gene content could be obtained in under 6 h from
      a subcultured isolate, less time than traditional phenotypic susceptibility
      testing.

PMID- 29021150
TI  - Identification of a selective and direct NLRP3 inhibitor to treat inflammatory
      disorders.
AB  - The NLRP3 inflammasome has been implicated in the pathogenesis of a wide variety
      of human diseases. A few compounds have been developed to inhibit NLRP3
      inflammasome activation, but compounds directly and specifically targeting NLRP3
      are still not available, so it is unclear whether NLRP3 itself can be targeted to
      prevent or treat diseases. Here we show that the compound CY-09 specifically
      blocks NLRP3 inflammasome activation. CY-09 directly binds to the ATP-binding
      motif of NLRP3 NACHT domain and inhibits NLRP3 ATPase activity, resulting in the
      suppression of NLRP3 inflammasome assembly and activation. Importantly, treatment
      with CY-09 shows remarkable therapeutic effects on mouse models of cryopyrin
      associated autoinflammatory syndrome (CAPS) and type 2 diabetes. Furthermore, CY
      09 is active ex vivo for monocytes from healthy individuals or synovial fluid
      cells from patients with gout. Thus, our results provide a selective and direct
      small-molecule inhibitor for NLRP3 and indicate that NLRP3 can be targeted in
      vivo to combat NLRP3-driven diseases.

PMID- 29021152
TI  - Evaluation of the Clinical Performance of the HPV-Risk Assay Using the VALGENT-3
      Panel.
AB  - Human papillomavirus (HPV) testing is increasingly being incorporated into
      cervical cancer screening. The Validation of HPV Genotyping Tests (VALGENT) is a
      framework designed to evaluate the clinical performance of various HPV tests
      relative to that of the validated and accepted comparator test in a formalized
      and uniform manner. The aim of this study was to evaluate the clinical
      performance of the HPV-Risk assay with samples from the VALGENT-3 panel and to
      compare its performance to that of the clinically validated Hybrid Capture 2
      assay (HC2). The VALGENT-3 panel comprises 1,300 consecutive samples from women
      participating in routine cervical cancer screening and is enriched with 300
      samples from women with abnormal cytology. DNA was extracted from original
      ThinPrep PreservCyt medium aliquots, and HPV testing was performed using the HPV
      Risk assay by investigators blind to the clinical data. HPV prevalence was
      analyzed, and the clinical performance of the HPV-Risk assay for the detection of
      cervical intraepithelial neoplasia grade 3 or worse (CIN3+) and CIN2 or worse
      (CIN2+) relative to the performance of HC2 was assessed. The sensitivity of the
      HPV-Risk assay for the detection of CIN3+ was similar to that of HC2 (relative
      sensitivity, 1.00; 95% confidence interval [CI], 0.95 to 1.05; P = 1.000), but
      the specificity of the HPV-Risk assay was significantly higher than that of HC2
      (relative specificity, 1.02; 95% CI, 1.01 to 1.04; P < 0.001). For the detection
      of CIN2+, similar results were obtained, with the relative sensitivity being 0.98
      (95% CI, 0.93 to 1.02; P = 0.257) and the relative specificity being 1.02 (95%
      CI, 1.01 to 1.03; P < 0.001). The performance of the HPV-Risk assay for the
      detection of CIN3+ and CIN2+ was noninferior to that of HC2, with all P values
      being <=0.006. In conclusion, the HPV-Risk assay demonstrated noninferiority to
      the clinically validated HC2 by the use of samples from the VALGENT-3 panel for
      test validation and comparison.

PMID- 29021153
TI  - Evaluation of the beta-Lacta Test for Detection of Extended-Spectrum-beta
      Lactamase (ESBL)-Producing Organisms Directly from Positive Blood Cultures by Use
      of Smudge Plates.

PMID- 29021154
TI  - Laboratory Validation of Xpert Chlamydia trachomatis/Neisseria gonorrhoeae and
      Trichomonas vaginalis Testing as Performed by Nurses at Three Primary Health Care
      Facilities in South Africa.

PMID- 29021155
TI  - Effects of Clinically Meaningful Concentrations of Antipseudomonal beta-Lactams
      on Time to Detection and Organism Growth in Blood Culture Bottles.
AB  - The effectiveness of antimicrobial binding resins present in blood culture (BC)
      bottles in removing meropenem, ceftolozane-tazobactam, and ceftazidime-avibactam
      is unknown. We assessed the time to detection (TTD) and growth of 2 Pseudomonas
      aeruginosa isolates in the presence of clinically meaningful concentrations of
      these antibiotics. Bactec Plus Aerobic/F and BacT/Alert FA Plus BC bottles were
      inoculated with one of two isolates (1 meropenem susceptible and 1 resistant),
      followed by fresh whole blood containing the peak, midpoint, or trough plasma
      concentrations for meropenem, ceftolozane-tazobactam, and ceftazidime-avibactam.
      Matching bottles were loaded into their respective detection instruments and a
      standard incubator at 37 degrees C, with TTD and CFU being monitored for up to 72
      h. Bacterial growth was observed for 11/48 (22.9%), 22/48 (45.8%), and 47/48
      (97.9%) of all BC bottles inoculated with the peak, midpoint, and trough
      concentrations, respectively (P <= 0.001). When P. aeruginosa was isolated, the
      TTD was typically <26 h, and no differences between Bactec and BacT/Alert bottles
      were observed. In both systems, meropenem was removed to a greater degree than
      were ceftolozane and ceftazidime; however, concentrations for all antibiotics
      remained above the MIC for the susceptible organisms at 12 h. BC bottles
      containing antibiotic binding resins may not sufficiently inactivate achievable
      concentrations of meropenem, ceftolozane-tazobactam, and ceftazidime-avibactam.
      The consistent identification of both P. aeruginosa isolates was observed only in
      the presence of antibiotic trough concentrations. To minimize false-negative BC
      results for patients already receiving these antibiotics, cultures should be
      collected just prior to the next dose, when antibiotic concentrations are lowest.

PMID- 29021156
TI  - Safety and Accuracy of Matrix-Assisted Laser Desorption Ionization-Time of Flight
      Mass Spectrometry for Identification of Highly Pathogenic Organisms.
AB  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) sample preparation methods, including the direct, on-plate formic
      acid, and ethanol/formic acid tube extraction methods, were evaluated for their
      ability to render highly pathogenic organisms nonviable and safe for handling in
      a biosafety level 2 laboratory. Of these, the tube extraction procedure was the
      most successful, with none of the tested strains surviving this sample
      preparation method. Tube extracts from several agents of bioterrorism and their
      near neighbors were analyzed in an eight-laboratory study to examine the utility
      of the Bruker Biotyper and Vitek MS MALDI-TOF MS systems and their in vitro
      diagnostic (IVD), research-use-only, and Security-Relevant databases, as
      applicable, to accurately identify these agents. Forty-six distinct strains of
      Bacillus anthracis, Yersinia pestis, Francisella tularensis, Burkholderia mallei,
      Burkholderia pseudomallei, Clostridium botulinum, Brucella melitensis, Brucella
      abortus, Brucella suis, and Brucella canis were extracted and distributed to
      participating laboratories for analysis. A total of 35 near-neighbor isolates
      were also analyzed.

PMID- 29021157
TI  - Ribosome flow model with extended objects.
AB  - We study a deterministic mechanistic model for the flow of ribosomes along the
      mRNA molecule, called the ribosome flow model with extended objects (RFMEO). This
      model encapsulates many realistic features of translation including non
      homogeneous transition rates along mRNA, the fact that every ribosome covers
      several codons, and the fact that ribosomes cannot overtake one another. The
      RFMEO is a mean-field approximation of an important model from statistical
      mechanics called the totally asymmetric simple exclusion process with extended
      objects (TASEPEO). We demonstrate that the RFMEO describes biophysical aspects of
      translation better than previous mean-field approximations, and that its
      predictions correlate well with those of TASEPEO. However, unlike TASEPEO, the
      RFMEO is amenable to rigorous analysis using tools from systems and control
      theory. We show that the ribosome density profile along the mRNA in the RFMEO
      converges to a unique steady-state density that depends on the length of the
      mRNA, the transition rates along it, and the number of codons covered by every
      ribosome, but not on the initial density of ribosomes along the mRNA. In
      particular, the protein production rate also converges to a unique steady state.
      Furthermore, if the transition rates along the mRNA are periodic with a common
      period T then the ribosome density along the mRNA and the protein production rate
      converge to a unique periodic pattern with period T, that is, the model entrains
      to periodic excitations in the transition rates. Analysis and simulations of the
      RFMEO demonstrate several counterintuitive results. For example, increasing the
      ribosome footprint may sometimes lead to an increase in the production rate.
      Also, for large values of the footprint the steady-state density along the mRNA
      may be quite complex (e.g. with quasi-periodic patterns) even for relatively
      simple (and non-periodic) transition rates along the mRNA. This implies that
      inferring the transition rates from the ribosome density may be non-trivial. We
      believe that the RFMEO could be useful for modelling, understanding and re
      engineering translation as well as other important biological processes.

PMID- 29021158
TI  - Hierarchical temporal structure in music, speech and animal vocalizations: jazz
      is like a conversation, humpbacks sing like hermit thrushes.
AB  - Humans talk, sing and play music. Some species of birds and whales sing long and
      complex songs. All these behaviours and sounds exhibit hierarchical structure
      syllables and notes are positioned within words and musical phrases, words and
      motives in sentences and musical phrases, and so on. We developed a new method to
      measure and compare hierarchical temporal structures in speech, song and music.
      The method identifies temporal events as peaks in the sound amplitude envelope,
      and quantifies event clustering across a range of timescales using Allan factor
      (AF) variance. AF variances were analysed and compared for over 200 different
      recordings from more than 16 different categories of signals, including
      recordings of speech in different contexts and languages, musical compositions
      and performances from different genres. Non-human vocalizations from two bird
      species and two types of marine mammals were also analysed for comparison. The
      resulting patterns of AF variance across timescales were distinct to each of four
      natural categories of complex sound: speech, popular music, classical music and
      complex animal vocalizations. Comparisons within and across categories indicated
      that nested clustering in longer timescales was more prominent when prosodic
      variation was greater, and when sounds came from interactions among individuals,
      including interactions between speakers, musicians, and even killer whales.
      Nested clustering also was more prominent for music compared with speech, and
      reflected beat structure for popular music and self-similarity across timescales
      for classical music. In summary, hierarchical temporal structures reflect the
      behavioural and social processes underlying complex vocalizations and musical
      performances.

PMID- 29021159
TI  - Suction effects in cratered surfaces.
AB  - It has been shown experimentally that cratered surfaces may have better adhesion
      properties than flat ones. However, the suction effect produced by the craters,
      which may be chiefly responsible for the improved adhesion, has not been properly
      modelled. This paper combines experimental, numerical simulation and analytical
      approaches towards developing a framework for quantifying the suction effect
      produced by isolated craters and cratered surfaces. The modelling approach
      emphasizes the essential role of large elastic deformation, while the airflow
      dynamics, microscopic mechanisms, like surface tension and air permeation, and
      rate-dependence are neglected. This approach is validated using experimental data
      for isolated hemi-spherical craters. The modelling approach is further applied to
      spherical cap (not necessarily hemi-spherical) craters with the objective of
      identifying optimal geometric and material properties, as well as the minimum
      preload necessary for attaining the maximum suction force. It is determined that
      stiff polymers with deep craters are capable of producing large suction forces.
      For soft materials, central to biomedical applications, large suction forces can
      be attained by reinforcing deep craters with thin stiff layers. Parametric
      optimization studies of reinforced craters reveal that some of them perform
      beyond common expectations. However, those high-performance reinforced craters
      are prone to surface instabilities, and therefore the practical use of such
      craters may be problematic.

PMID- 29021160
TI  - Off-axis electron holography of bacterial cells and magnetic nanoparticles in
      liquid.
AB  - The mapping of electrostatic potentials and magnetic fields in liquids using
      electron holography has been considered to be unrealistic. Here, we show that
      hydrated cells of Magnetospirillum magneticum strain AMB-1 and assemblies of
      magnetic nanoparticles can be studied using off-axis electron holography in a
      fluid cell specimen holder within the transmission electron microscope.
      Considering that the holographic object and reference wave both pass through
      liquid, the recorded electron holograms show sufficient interference fringe
      contrast to permit reconstruction of the phase shift of the electron wave and
      mapping of the magnetic induction from bacterial magnetite nanocrystals. We
      assess the challenges of performing in situ magnetization reversal experiments
      using a fluid cell specimen holder, discuss approaches for improving spatial
      resolution and specimen stability, and outline future perspectives for studying
      scientific phenomena, ranging from interparticle interactions in liquids and
      electrical double layers at solid-liquid interfaces to biomineralization and the
      mapping of electrostatic potentials associated with protein aggregation and
      folding.

PMID- 29021161
TI  - Network-based approaches to quantify multicellular development.
AB  - Multicellularity and cellular cooperation confer novel functions on organs
      following a structure-function relationship. How regulated cell migration,
      division and differentiation events generate cellular arrangements has been
      investigated, providing insight into the regulation of genetically encoded
      patterning processes. Much less is known about the higher-order properties of
      cellular organization within organs, and how their functional coordination
      through global spatial relations shape and constrain organ function. Key
      questions to be addressed include: why are cells organized in the way they are?
      What is the significance of the patterns of cellular organization selected for by
      evolution? What other configurations are possible? These may be addressed through
      a combination of global cellular interaction mapping and network science to
      uncover the relationship between organ structure and function. Using this
      approach, global cellular organization can be discretized and analysed, providing
      a quantitative framework to explore developmental processes. Each of the local
      and global properties of integrated multicellular systems can be analysed and
      compared across different tissues and models in discrete terms. Advances in high
      resolution microscopy and image analysis continue to make cellular interaction
      mapping possible in an increasing variety of biological systems and tissues,
      broadening the further potential application of this approach. Understanding the
      higher-order properties of complex cellular assemblies provides the opportunity
      to explore the evolution and constraints of cell organization, establishing
      structure-function relationships that can guide future organ design.

PMID- 29021162
TI  - Electronic and vibrational properties of carotenoids: from in vitro to in vivo.
AB  - Carotenoids are among the most important organic compounds present in Nature and
      play several essential roles in biology. Their configuration is responsible for
      their specific photophysical properties, which can be tailored by changes in
      their molecular structure and in the surrounding environment. In this review, we
      give a general description of the main electronic and vibrational properties of
      carotenoids. In the first part, we describe how the electronic and vibrational
      properties are related to the molecular configuration of carotenoids. We show how
      modifications to their configuration, as well as the addition of functional
      groups, can affect the length of the conjugated chain. We describe the concept of
      effective conjugation length, and its relationship to the S0 -> S2 electronic
      transition, the decay rate of the S1 energetic level and the frequency of the nu1
      Raman band. We then consider the dependence of these properties on extrinsic
      parameters such as the polarizability of their environment, and how this
      information (S0 -> S2 electronic transition, nu1 band position, effective
      conjugation length and polarizability of the environment) can be represented on a
      single graph. In the second part of the review, we use a number of specific
      examples to show that the relationships can be used to disentangle the different
      mechanisms tuning the functional properties of protein-bound carotenoids.

PMID- 29021164
TI  - Investigation of microvascular morphological measures for skeletal muscle tissue
      oxygenation by image-based modelling in three dimensions.
AB  - The supply of oxygen in sufficient quantity is vital for the correct functioning
      of all organs in the human body, especially for skeletal muscle during exercise.
      Traditionally, microvascular oxygen supply capability is assessed by the analysis
      of morphological measures on transverse cross-sections of muscle, e.g. capillary
      density or capillary-to-fibre ratio. In this work, we investigate the
      relationship between microvascular structure and muscle tissue oxygenation in
      mice. Phase contrast imaging was performed using synchrotron radiation computed
      tomography (SR CT) to visualize red blood cells (RBCs) within the
      microvasculature in mouse soleus muscle. Image-based mathematical modelling of
      the oxygen diffusion from the RBCs into the muscle tissue was subsequently
      performed, as well as a morphometric analysis of the microvasculature. The mean
      tissue oxygenation was then compared with the morphological measures of the
      microvasculature. RBC volume fraction and spacing (mean distance of any point in
      tissue to the closest RBC) emerged as the best predictors for muscle tissue
      oxygenation, followed by length density (summed RBC length over muscle volume).
      The two-dimensional measures of capillary density and capillary-to-fibre ratio
      ranked last. We, therefore, conclude that, in order to assess the states of
      health of muscle tissue, it is advisable to rely on three-dimensional
      morphological measures rather than on the traditional two-dimensional measures.

PMID- 29021163
TI  - Resource-driven encounters among consumers and implications for the spread of
      infectious disease.
AB  - Animals share a variety of common resources, which can be a major driver of
      conspecific encounter rates. In this work, we implement a spatially explicit
      mathematical model for resource visitation behaviour in order to examine how
      changes in resource availability can influence the rate of encounters among
      consumers. Using simulations and asymptotic analysis, we demonstrate that, under
      a reasonable set of assumptions, the relationship between resource availability
      and consumer conspecific encounters is not monotonic. We characterize how the
      maximum encounter rate and associated critical resource density depend on system
      parameters like consumer density and the maximum distance from which consumers
      can detect and respond to resources. The assumptions underlying our theoretical
      model and analysis are motivated by observations of large aggregations of black
      backed jackals at carcasses generated by seasonal outbreaks of anthrax among
      herbivores in Etosha National Park, Namibia. As non-obligate scavengers, black
      backed jackals use carcasses as a supplemental food resource when they are
      available. While jackals do not appear to acquire disease from ingesting anthrax
      carcasses, changes in their movement patterns in response to changes in carcass
      abundance do alter jackals' conspecific encounter rate in ways that may affect
      the transmission dynamics of other diseases, such as rabies. Our theoretical
      results provide a method to quantify and analyse the hypothesis that the outbreak
      of a fatal disease among herbivores can potentially facilitate outbreaks of an
      entirely different disease among jackals. By analysing carcass visitation data,
      we find support for our model's prediction that the number of conspecific
      encounters at resource sites decreases with additional increases in resource
      availability. Whether or not this site-dependent effect translates to an overall
      decrease in encounters depends, unexpectedly, on the relationship between the
      maximum distance of detection and the resource density.

PMID- 29021165
TI  - Preclinical modeling highlights the therapeutic potential of hematopoietic stem
      cell gene editing for correction of SCID-X1.
AB  - Targeted genome editing in hematopoietic stem/progenitor cells (HSPCs) is an
      attractive strategy for treating immunohematological diseases. However, the
      limited efficiency of homology-directed editing in primitive HSPCs constrains the
      yield of corrected cells and might affect the feasibility and safety of clinical
      translation. These concerns need to be addressed in stringent preclinical models
      and overcome by developing more efficient editing methods. We generated a
      humanized X-linked severe combined immunodeficiency (SCID-X1) mouse model and
      evaluated the efficacy and safety of hematopoietic reconstitution from limited
      input of functional HSPCs, establishing thresholds for full correction upon
      different types of conditioning. Unexpectedly, conditioning before HSPC infusion
      was required to protect the mice from lymphoma developing when transplanting
      small numbers of progenitors. We then designed a one-size-fits-all IL2RG
      (interleukin-2 receptor common gamma-chain) gene correction strategy and, using
      the same reagents suitable for correction of human HSPC, validated the edited
      human gene in the disease model in vivo, providing evidence of targeted gene
      editing in mouse HSPCs and demonstrating the functionality of the IL2RG-edited
      lymphoid progeny. Finally, we optimized editing reagents and protocol for human
      HSPCs and attained the threshold of IL2RG editing in long-term repopulating cells
      predicted to safely rescue the disease, using clinically relevant HSPC sources
      and highly specific zinc finger nucleases or CRISPR (clustered regularly
      interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9).
      Overall, our work establishes the rationale and guiding principles for clinical
      translation of SCID-X1 gene editing and provides a framework for developing gene
      correction for other diseases.

PMID- 29021166
TI  - An analysis of IL-36 signature genes and individuals with IL1RL2 knockout
      mutations validates IL-36 as a psoriasis therapeutic target.
AB  - Interleukin (IL)-36alpha, IL-36beta, and IL-36gamma are innate mediators of acute
      epithelial inflammation. We sought to demonstrate that these cytokines are also
      required for the pathogenesis of plaque psoriasis, a common and chronic skin
      disorder, caused by abnormal T helper 17 (TH17) cell activation. To investigate
      this possibility, we first defined the genes that are induced by IL-36 cytokines
      in primary human keratinocytes. This enabled us to demonstrate a significant IL
      36 signature among the transcripts that are up-regulated in plaque psoriasis and
      the susceptibility loci associated with the disease in genome-wide studies. Next,
      we investigated the impact of in vivo and ex vivo IL-36 receptor blockade using a
      neutralizing antibody or a recombinant antagonist. Both inhibitors had marked
      anti-inflammatory effects on psoriatic skin, demonstrated by statistically
      significant reductions in IL-17 expression, keratinocyte activation, and
      leukocyte infiltration. Finally, we explored the potential safety profile
      associated with IL-36 blockade by phenotyping 12 individuals carrying knockout
      mutations of the IL-36 receptor gene. We found that normal immune function was
      broadly preserved in these individuals, suggesting that IL-36 signaling
      inhibition would not substantially compromise host defenses. These observations,
      which integrate the results of transcriptomics and model system analysis, pave
      the way for early-stage clinical trials of IL-36 antagonists.

PMID- 29021167
TI  - High-density lipoprotein delivered after myocardial infarction increases cardiac
      glucose uptake and function in mice.
AB  - Protecting the heart after an acute coronary syndrome is a key therapeutic goal
      to support cardiac recovery and prevent progression to heart failure. A potential
      strategy is to target cardiac glucose metabolism at the early stages after
      ischemia when glycolysis is critical for myocyte survival. Building on our
      discovery that high-density lipoprotein (HDL) modulates skeletal muscle glucose
      metabolism, we now demonstrate that a single dose of reconstituted HDL (rHDL)
      delivered after myocardial ischemia increases cardiac glucose uptake, reduces
      infarct size, and improves cardiac remodeling in association with enhanced
      functional recovery in mice. These findings applied equally to metabolically
      normal and insulin-resistant mice. We further establish direct effects of HDL on
      cardiomyocyte glucose uptake, glycolysis, and glucose oxidation via the Akt
      signaling pathway within 15 min of reperfusion. These data support the use of
      infusible HDL preparations for management of acute coronary syndromes in the
      setting of primary percutaneous interventions.

PMID- 29021168
TI  - Functional ultrasound imaging of brain activity in human newborns.
AB  - Functional neuroimaging modalities are crucial for understanding brain function,
      but their clinical use is challenging. Recently, the use of ultrasonic plane
      waves transmitted at ultrafast frame rates was shown to allow for the
      spatiotemporal identification of brain activation through neurovascular coupling
      in rodents. Using a customized flexible and noninvasive headmount, we demonstrate
      in human neonates that real-time functional ultrasound imaging (fUSI) is feasible
      by combining simultaneous continuous video-electroencephalography (EEG) recording
      and ultrafast Doppler (UfD) imaging of the brain microvasculature. fUSI detected
      very small cerebral blood volume variations in the brains of neonates that
      closely correlated with two different sleep states defined by EEG recordings.
      fUSI was also used to assess brain activity in two neonates with congenital
      abnormal cortical development enabling elucidation of the dynamics of neonatal
      seizures with high spatiotemporal resolution (200 MUm for UfD and 1 ms for EEG).
      fUSI was then applied to track how waves of vascular changes were propagated
      during interictal periods and to determine the ictal foci of the seizures.
      Imaging the human brain with fUSI enables high-resolution identification of brain
      activation through neurovascular coupling and may provide new insights into
      seizure analysis and the monitoring of brain function.

PMID- 29021169
TI  - Punctuated invasion of water, ice, snow and terrestrial ecozones by segmented
      worms (Oligochaeta: Enchytraeidae: Mesenchytraeus).
AB  - Segmented worms (Annelida) are among the most successful animal inhabitants of
      extreme environments worldwide. An unusual group of enchytraeid oligochaetes of
      genus Mesenchytraeus are abundant in the Pacific northwestern region of North
      America and occupy geographically proximal ecozones ranging from low elevation
      rainforests and waterways to high altitude glaciers. Along this altitudinal
      transect, Mesenchytraeus representatives from disparate habitat types were
      collected and subjected to deep mitochondrial and nuclear phylogenetic analyses.
      Our data identify significant topological discordance among gene trees, and near
      equivalent interspecific divergence levels indicative of a rapid radiation event.
      Collectively, our results identify a Mesenchytraeus 'explosion' coincident with
      mountain building in the Pacific northwestern region that gave rise to closely
      related aquatic, ice, snow and terrestrial worms.

PMID- 29021170
TI  - A human model for primate personality.
AB  - In this article, I review the literature to determine how successful the latent
      trait theory model of personality from differential psychology has been for
      studying personality in non-human primates. The evidence for the success of this
      model is quite good, and offers insights and directions for personality research
      in primates and other animals. This, I conclude, stems from (i) the human trait
      model's simplicity, and (ii) the fact that the human differential model of
      personality developed in the face of harsh criticism, which led researchers to
      test and refine their models.

PMID- 29021171
TI  - Combined effects of night warming and light pollution on predator-prey
      interactions.
AB  - Interactions between multiple anthropogenic environmental changes can drive non
      additive effects in ecological systems, and the non-additive effects can in turn
      be amplified or dampened by spatial covariation among environmental changes. We
      investigated the combined effects of night-time warming and light pollution on
      pea aphids and two predatory ladybeetle species. As expected, neither night-time
      warming nor light pollution changed the suppression of aphids by the ladybeetle
      species that forages effectively in darkness. However, for the more-visual
      predator, warming and light had non-additive effects in which together they
      caused much lower aphid abundances. These results are particularly relevant for
      agriculture near urban areas that experience both light pollution and warming
      from urban heat islands. Because warming and light pollution can have non
      additive effects, predicting their possible combined consequences over broad
      spatial scales requires knowing how they co-occur. We found that night-time
      temperature change since 1949 covaried positively with light pollution, which has
      the potential to increase their non-additive effects on pea aphid control by 70%
      in US alfalfa. Our results highlight the importance of non-additive effects of
      multiple environmental factors on species and food webs, especially when these
      factors co-occur.

PMID- 29021172
TI  - Genital interactions during simulated copulation among marine mammals.
AB  - Genitalia are morphologically variable across many taxa and in physical contact
      during intromission, but little is known about how variation in form correlates
      with function during copulation. Marine mammals offer important insights into the
      evolutionary forces that act on genital morphology because they have diverse
      genitalia and are adapted to aquatic living and mating. Cetaceans have a
      fibroelastic penis and muscular vaginal folds, while pinnipeds have a baculum and
      lack vaginal folds. We examined copulatory fit in naturally deceased marine
      mammals to identify anatomical landmarks in contact during copulation and the
      potential depth of penile penetration into the vagina. Excised penises were
      artificially inflated to erection with pressurized saline and compared with
      silicone vaginal endocasts and within excised vaginas in simulated copulation
      using high-resolution, diffusible iodine-based, contrast-enhanced computed
      tomography. We found evidence suggestive of both congruent and antagonistic
      genital coevolution, depending on the species. We suggest that sexual selection
      influences morphological shape. This study improves our understanding of how
      mechanical interactions during copulation influence the shape of genitalia and
      affect fertility, and has broad applications to other taxa and species
      conservation.

PMID- 29021173
TI  - Heterochrony in the evolution of Trinidadian guppy offspring size: maturation
      along a uniform ontogenetic trajectory.
AB  - The size and maturity of Trinidadian guppy (Poecilia reticulata) offspring vary
      among populations adapted to environments of differential predation. Guppy
      offspring born to low-predation, high-competition environments are larger and
      more mature than their high-predation ancestors. Here we ask: what specific
      changes in developmental or birth timing occur to produce the larger, more mature
      neonates? We collected specimens across the perinatal window of development from
      five populations and quantified musculoskeletal maturation. We found that all
      populations undergo similar ontogenetic trajectories in skeletal and muscle
      acquisition; the only difference among populations is when neonates emerge along
      the trajectory. The smallest neonates are born with 20% of their skeleton
      ossified, whereas the largest neonates are born with over 70% of their skeleton
      ossified. The area of the major jaw-closing muscle is relatively larger in larger
      offspring, scaling with length as L2.5 The size range over which offspring are
      birthed among populations sits along the steepest part of the size-maturity
      relationship, which provides a large marginal increase in fitness for the high
      competition female. Because of the functional effects of producing more mature
      offspring at birth, offspring size may be the first and most critical life
      history trait selected upon in highly competitive environments.

PMID- 29021174
TI  - Nutritional geometry of paternal effects on embryo mortality.
AB  - Well-established causal links exist between maternal nutritional deficits and
      embryo health and viability. By contrast, environmental effects operating through
      the father that could influence embryo mortality have seldom been examined. Yet,
      ejaculates can require non-trivial resource allocation, and seminal plasma
      components are increasingly recognized to exert wide-ranging effects on females
      and offspring, so paternal dietary effects on the embryo should be expected. We
      test for effects of varying levels of protein (P), carbohydrate (C) and caloric
      load in adult male diet on embryo mortality in Drosophila melanogaster We
      demonstrate that macronutrient balance and caloric restriction exert significant
      effects, and that nutritional effects are more impactful when a prior mating has
      occurred. Once-mated males produced embryos with marginally elevated mortality
      under high-caloric densities and a 1 : 8 P : C ratio. In contrast, embryos
      produced by twice-mated males were significantly more likely to die under male
      caloric restriction, an outcome that may have resulted from shifts in ejaculate
      quality and/or epigenetic paternal effects. Body nutrient reserves were strongly
      and predictably altered by diet, and body condition, in turn, was negatively
      related to embryo mortality. Thus, sire nutritional history and resultant shifts
      in metabolic state predict embryo viability and post-fertilization fitness
      outcomes.

PMID- 29021175
TI  - Species identity and depth predict bleaching severity in reef-building corals:
      shall the deep inherit the reef?
AB  - Mass bleaching associated with unusually high sea temperatures represents one of
      the greatest threats to corals and coral reef ecosystems. Deeper reef areas are
      hypothesized as potential refugia, but the susceptibility of Scleractinian
      species over depth has not been quantified. During the most severe bleaching
      event on record, we found up to 83% of coral cover severely affected on Maldivian
      reefs at a depth of 3-5 m, but significantly reduced effects at 24-30 m. Analysis
      of 153 species' responses showed depth, shading and species identity had strong,
      significant effects on susceptibility. Overall, 73.3% of the shallow-reef
      assemblage had individuals at a depth of 24-30 m with reduced effects,
      potentially mitigating local extinction and providing a source of recruits for
      population recovery. Although susceptibility was phylogenetically constrained,
      species-level effects caused most lineages to contain some partially resistant
      species. Many genera showed wide variation between species, including Acropora,
      previously considered highly susceptible. Extinction risk estimates showed
      species and lineages of concern and those likely to dominate following repeated
      events. Our results show that deeper reef areas provide refuge for a large
      proportion of Scleractinian species during severe bleaching events and that the
      deepest occurring individuals of each population have the greatest potential to
      survive and drive reef recovery.

PMID- 29021176
TI  - Parsimony and maximum-likelihood phylogenetic analyses of morphology do not
      generally integrate uncertainty in inferring evolutionary history: a response to
      Brown et al.

PMID- 29021177
TI  - Men's preferences for women's body odours are not associated with human leucocyte
      antigen.
AB  - Body odours reportedly portray information about an individual's genotype at the
      major histocompatibility complex (MHC, called human leucocyte antigen, HLA, in
      humans). While there is strong experimental support for MHC-associated mating
      behaviour in animals, the situation in humans is more complex. A lot of effort
      has been spent on testing HLA-associated odour preferences of women. To date,
      only very few studies have looked at HLA-linked olfactory preferences in men and
      these studies have revealed inconsistent results. Here, we investigate men's HLA
      associated preferences for women's body odours. Importantly, and in contrast to
      previous studies, these odours were gathered at peak fertility (i.e. just before
      ovulation) when any HLA-associated odour preferences should be strongest. We
      scrutinized whether men's preference for women's body odours is influenced by (i)
      the number of shared HLA alleles between men and women, (ii) HLA heterozygosity,
      and (iii) the frequency of rare HLA alleles. We found that men could readily
      differentiate between odours they found attractive and odours they found less
      attractive, but that these preferences were not associated with HLA.
      Specifically, men did not prefer odours from women who are HLA dissimilar, HLA
      heterozygous, or who have rare HLA alleles. Together, these findings suggest that
      HLA has no effect on men's odour preferences.

PMID- 29021178
TI  - Evolutionary contribution to coexistence of competitors in microbial food webs.
AB  - The theory of species coexistence is a key concept in ecology that has received
      much attention. The role of rapid evolution for determining species coexistence
      is still poorly understood although evolutionary change on ecological time-scales
      has the potential to change almost any ecological process. The influence of
      evolution on coexistence can be especially pronounced in microbial communities
      where organisms often have large population sizes and short generation times.
      Previous work on coexistence has assumed that traits involved in resource use and
      species interactions are constant or change very slowly in terms of ecological
      time-scales. However, recent work suggests that these traits can evolve rapidly.
      Nevertheless, the importance of rapid evolution to coexistence has not been
      tested experimentally. Here, we show how rapid evolution alters the frequency of
      two bacterial competitors over time when grown together with specialist consumers
      (bacteriophages), a generalist consumer (protozoan) and all in combination. We
      find that consumers facilitate coexistence in a manner consistent with classic
      ecological theory. However, through disentangling the relative contributions of
      ecology (changes in consumer abundance) and evolution (changes in traits
      mediating species interactions) on the frequency of the two competitors over
      time, we find differences between the consumer types and combinations. Overall,
      our results indicate that the influence of evolution on species coexistence
      strongly depends on the traits and species interactions considered.

PMID- 29021179
TI  - Bayesian and likelihood phylogenetic reconstructions of morphological traits are
      not discordant when taking uncertainty into consideration: a comment on Puttick
      et al.
AB  - Puttick et al. (2017 Proc. R. Soc. B284, 20162290 (doi:10.1098/rspb.2016.2290))
      performed a simulation study to compare accuracy among methods of inferring
      phylogeny from discrete morphological characters. They report that a Bayesian
      implementation of the Mk model (Lewis 2001 Syst. Biol.50, 913-925
      (doi:10.1080/106351501753462876)) was most accurate (but with low resolution),
      while a maximum-likelihood (ML) implementation of the same model was least
      accurate. They conclude by strongly advocating that Bayesian implementations of
      the Mk model should be the default method of analysis for such data. While we
      appreciate the authors' attempt to investigate the accuracy of alternative
      methods of analysis, their conclusion is based on an inappropriate comparison of
      the ML point estimate, which does not consider confidence, with the Bayesian
      consensus, which incorporates estimation credibility into the summary tree. Using
      simulation, we demonstrate that ML and Bayesian estimates are concordant when
      confidence and credibility are comparably reflected in summary trees, a result
      expected from statistical theory. We therefore disagree with the conclusions of
      Puttick et al. and consider their prescription of any default method to be poorly
      founded. Instead, we recommend caution and thoughtful consideration of the model
      or method being applied to a morphological dataset.

PMID- 29021180
TI  - Bluetongue virus spread in Europe is a consequence of climatic, landscape and
      vertebrate host factors as revealed by phylogeographic inference.
AB  - Spatio-temporal patterns of the spread of infectious diseases are commonly driven
      by environmental and ecological factors. This is particularly true for vector
      borne diseases because vector populations can be strongly affected by host
      distribution as well as by climatic and landscape variables. Here, we aim to
      identify environmental drivers for bluetongue virus (BTV), the causative agent of
      a major vector-borne disease of ruminants that has emerged multiple times in
      Europe in recent decades. In order to determine the importance of climatic,
      landscape and host-related factors affecting BTV diffusion across Europe, we
      fitted different phylogeographic models to a dataset of 113 time-stamped and geo
      referenced BTV genomes, representing multiple strains and serotypes. Diffusion
      models using continuous space revealed that terrestrial habitat below 300 m
      altitude, wind direction and higher livestock densities were associated with
      faster BTV movement. Results of discrete phylogeographic analysis involving
      generalized linear models broadly supported these findings, but varied
      considerably with the level of spatial partitioning. Contrary to common
      perception, we found no evidence for average temperature having a positive effect
      on BTV diffusion, though both methodological and biological reasons could be
      responsible for this result. Our study provides important insights into the
      drivers of BTV transmission at the landscape scale that could inform predictive
      models of viral spread and have implications for designing control strategies.

PMID- 29021181
TI  - Variability in larval gut pH regulation defines sensitivity to ocean
      acidification in six species of the Ambulacraria superphylum.
AB  - The unusual rate and extent of environmental changes due to human activities may
      exceed the capacity of marine organisms to deal with this phenomenon. The
      identification of physiological systems that set the tolerance limits and their
      potential for phenotypic buffering in the most vulnerable ontogenetic stages
      become increasingly important to make large-scale projections. Here, we
      demonstrate that the differential sensitivity of non-calcifying Ambulacraria
      (echinoderms and hemichordates) larvae towards simulated ocean acidification is
      dictated by the physiology of their digestive systems. Gastric pH regulation upon
      experimental ocean acidification was compared in six species of the superphylum
      Ambulacraria. We observed a strong correlation between sensitivity to ocean
      acidification and the ability to regulate gut pH. Surprisingly, species with
      tightly regulated gastric pH were more sensitive to ocean acidification. This
      study provides evidence that strict maintenance of highly alkaline conditions in
      the larval gut of Ambulacraria early life stages may dictate their sensitivity to
      decreases in seawater pH. These findings highlight the importance of identifying
      and understanding pH regulatory systems in marine larval stages that may
      contribute to substantial energetic challenges under near-future ocean
      acidification scenarios.

PMID- 29021182
TI  - Evolution in temperature-dependent phytoplankton traits revealed from a sediment
      archive: do reaction norms tell the whole story?
AB  - The high evolutionary potential of phytoplankton species allows them to rapidly
      adapt to global warming. Adaptations may occur in temperature-dependent traits,
      such as growth rate, cell size and life cycle processes. Using resurrection
      experiments with resting stages from living sediment archives, it is possible to
      investigate whether adaptation occurred. For this study, we revived resting cysts
      of the spring bloom dinoflagellate Apocalathium malmogiense from recent and 100
      year-old sediment layers from the Gulf of Finland, and compared temperature
      dependent traits of recent and historic strains along a temperature gradient. We
      detected no changes in growth rates and cell sizes but a significant difference
      between recent and historic strains regarding resting cyst formation. The
      encystment rate of recent strains was significantly lower compared with historic
      strains which we interpret as an indication of adaptation to higher and more
      rapidly increasing spring temperatures. Low encystment rates may allow for bloom
      formation even if the threshold temperature inducing a loss of actively growing
      cells through resting cyst formation is exceeded. Our findings reveal that
      phenotypic responses of phytoplankton to changing temperature conditions may
      include hidden traits such as life cycle processes and their regulation
      mechanisms. This study emphasizes the potential of living sediment archives to
      investigate plankton responses and adaptation to global warming.

PMID- 29021184
TI  - Radiologist shortage leaves patient care at risk, warns royal college.

PMID- 29021183
TI  - The evolution of cooperation in simple molecular replicators.
AB  - In order for the first genomes to evolve, independent replicators had to act
      cooperatively, with some reducing their own replication rate to help copy others.
      It has been argued that limited diffusion explains this early cooperation.
      However, social evolution models have shown that limited diffusion on its own
      often does not favour cooperation. Here we model early replicators using social
      evolution tools. We show that: (i) replicators can be considered to be
      cooperating as a result of kin selection; (ii) limited diffusion on its own does
      not favour cooperation; and (iii) the addition of overlapping generations,
      probably a general trait of molecular replicators, promotes cooperation. These
      results suggest key life-history features in the evolution of the genome and that
      the same factors can favour cooperation across the entire tree of life.

PMID- 29021185
TI  - Outsourcing review of GP referrals to private companies: who ultimately gains?

PMID- 29021186
TI  - Torture victims were unlawfully detained despite doctors' concerns.

PMID- 29021187
TI  - Complexity of primary care is barrier to physician associates, say GPs.

PMID- 29021188
TI  - Is follow up chest X-ray required in children with round pneumonia?

PMID- 29021189
TI  - Presence of atopy increases the risk of asthma relapse.
AB  - OBJECTIVES: To describe the point prevalence of respiratory viruses/atypical
      bacteria using PCR and evaluate the impact of respiratory viruses/atypical
      bacteria and atopy on acute severity and clinical recovery in children with
      hospitalised and non-hospitalised asthma exacerbations. DESIGN: This was a
      prospective study performed during 2009-2011. SETTING: The study was performed in
      the emergency departments of two hospitals. PATIENTS: 244 children aged 2-16
      years presenting with acute asthma to the emergency departments were recruited. A
      nasopharyngeal aspirate and allergen skin prick test were performed. MAIN OUTCOME
      MEASURES: The outcomes were divided into (1) acute severity outcomes (Australian
      National Asthma Council assessment, hospitalisation, Functional Severity Scale,
      Acute Asthma Score, asthma quality of life questionnaires for parents (PACQLQ) on
      presentation, asthma diary scores (ADS) on presentation and length of
      hospitalisation) and (2) recovery outcomes (PACQLQ for 21 days, ADS for 14 days
      and representation for asthma for 21 days). RESULTS: PCR for viruses/atypical
      bacteria was positive in 81.7% of children (75.1% human rhinovirus, codetection
      in 14.2%). Mycoplasma pneumoniae and Chlamydophila pneumoniae were rarely
      detected. The presence of micro-organisms had little impact on acute asthma or
      recovery outcomes. Children with atopy were significantly more likely to relapse
      and represent for medical care by day 14 (OR 1.11, 95% CI 1.00 to 1.23).
      CONCLUSIONS: The presence of any viruses is associated with asthma exacerbations
      but does not appear to influence asthma recovery. In contrast, atopy is
      associated with asthma relapse. M. pneumoniae and C. pneumoniae are rare triggers
      of acute asthma in young children.

PMID- 29021190
TI  - Spending on junk food advertising is nearly 30 times what government spends on
      promoting healthy eating.

PMID- 29021192
TI  - Orderly recruitment of thermoeffectors in resting humans.
AB  - The recruitment of thermoeffectors, including thermoregulatory behavior, relative
      to changes in body temperature has not been quantified in humans. We tested the
      hypothesis that changes in skin blood flow, behavior, and sweating or metabolic
      rate are initiated with increasing changes in mean skin temperature (Tskin) in
      resting humans. While wearing a water-perfused suit, 12 healthy young adults
      underwent heat (Heat) and cold stress (Cold) that induced gradual changes in
      Tskin. Subjects controlled the temperature of their dorsal neck to their
      perceived thermal comfort. Thus neck skin temperature provided an index of
      thermoregulatory behavior. Neck skin temperature (Tskin), core temperature
      (Tcore), metabolic rate, sweat rate, and nonglabrous skin blood flow were
      measured continually. Data were analyzed using segmental regression analysis,
      providing an index of thermoeffector activation relative to changes in Tskin. In
      Heat, increases in skin blood flow were observed with the smallest elevations in
      Tskin ( P < 0.01). Thermal behavior was initiated with an increase in Tskin of
      2.4 +/- 1.3 degrees C (mean +/- SD, P = 0.04), while sweating was observed with
      further elevations in Tskin (3.4 +/- 0.5 degrees C, P = 0.04), which coincided
      with increases in Tcore ( P = 0.98). In Cold, reductions in skin blood flow
      occurred with the smallest decrease in Tskin ( P < 0.01). Thermal behavior was
      initiated with a Tskin decrease of 1.5 +/- 1.3 degrees C, while metabolic rate (
      P = 0.10) and Tcore ( P = 0.76) did not change throughout. These data indicate
      that autonomic and behavioral thermoeffectors are recruited in coordination with
      one another and likely in an orderly manner relative to the comparative
      physiological cost.

PMID- 29021193
TI  - Domestic violence is poorly covered in medical training, study finds.

PMID- 29021191
TI  - Enhancement of phrenic long-term facilitation following repetitive acute
      intermittent hypoxia is blocked by the glycolytic inhibitor 2-deoxyglucose.
AB  - Moderate acute intermittent hypoxia (mAIH) elicits a form of respiratory motor
      plasticity known as phrenic long-term facilitation (pLTF). Preconditioning with
      modest protocols of chronic intermittent hypoxia enhances pLTF, demonstrating
      pLTF metaplasticity. Since "low-dose" protocols of repetitive acute intermittent
      hypoxia (rAIH) show promise as a therapeutic modality to restore respiratory (and
      nonrespiratory) motor function in clinical disorders with compromised breathing,
      we tested 1) whether preconditioning with a mild rAIH protocol enhances pLTF and
      hypoglossal (XII) LTF and 2) whether the enhancement is regulated by glycolytic
      flux. In anesthetized, paralyzed, and ventilated adult male Lewis rats, mAIH
      (three 5-min episodes of 10% O2) elicited pLTF (pLTF at 60 min post-mAIH: 49 +/-
      5% baseline). rAIH preconditioning (ten 5-min episodes of 11% O2/day with 5-min
      normoxic intervals, 3 times per week, for 4 wk) significantly enhanced pLTF (100
      +/- 16% baseline). XII LTF was unaffected by rAIH. When glycolytic flux was
      inhibited by 2-deoxy-d-glucose (2-DG) administered via drinking water (~80 mg.kg
      1.day-1), pLTF returned to normal levels (58 +/- 8% baseline); 2-DG had no effect
      on pLTF in normoxia-pretreated rats (59 +/- 7% baseline). In ventral cervical
      (C4/5) spinal homogenates, rAIH increased inducible nitric oxide synthase mRNA
      vs. normoxic controls, an effect blocked by 2-DG. However, there were no
      detectable effects of rAIH or 2-DG on several molecules associated with phrenic
      motor plasticity, including serotonin 2A, serotonin 7, brain-derived neurotrophic
      factor, tropomyosin receptor kinase B, or VEGF mRNA. We conclude that modest, but
      prolonged, rAIH elicits pLTF metaplasticity and that a drug known to inhibit
      glycolytic flux (2-DG) blocks pLTF enhancement.

PMID- 29021194
TI  - NHS pay cap has been scrapped, says Hunt.

PMID- 29021195
TI  - Data, data everywhere: the challenges of personalised medicine.

PMID- 29021197
TI  - Allyson Pollock: Tackling risks and harms.

PMID- 29021196
TI  - NF-kappaB-dependent upregulation of (pro)renin receptor mediates high-NaCl
      induced apoptosis in mouse inner medullary collecting duct cells.
AB  - (Pro)renin receptor (PRR), a component of the renin-angiotensin system, has
      emerged as a new regulator of collecting duct function. The present study was
      designed to investigate the role of PRR in high salt-induced apoptosis in
      cultured mouse inner medullary collecting duct cells, mIMCD-K2 cells. Exposure to
      high NaCl at 550 mosM/kgH2O increased PRR protein abundance, as did exposure to
      mannitol, sodium gluconate, or choline chloride. This was accompanied by
      upregulation of the abundance of phosphorylated NF-kappaB p65 protein. NF-kappaB
      inhibition with QNZ, caffeic acid phenethyl ester, or small interfering RNA
      (siRNA)-mediated silencing of NF-kappaB p65 attenuated high-NaCl-induced PRR
      upregulation. Exposure to high salt for 24 h induced apoptosis, as assessed by
      immunoblotting and immunocytochemistry analysis of cleaved caspase-3 and flow
      cytometry analysis of the number of apoptotic cells. High-NaCl-induced apoptosis
      was attenuated by a PRR decoy inhibitor, PRO20, or siRNA-mediated silencing of NF
      kappaB p65. These results show that induction of PRR expression by exposure to
      high NaCl occurs through activation of NF-kappaB, thus contributing to cell
      apoptosis.

PMID- 29021199
TI  - Communicating with relatives.

PMID- 29021200
TI  - David Oliver: How much information should patients' families expect on acute
      wards?

PMID- 29021201
TI  - High Court will hear class action against metal-on-metal hip manufacturer.

PMID- 29021202
TI  - Adjunctive antibiotics for drained skin abscesses improve clinical cure rate.

PMID- 29021203
TI  - Sixty seconds on . . . concurrent surgery.

PMID- 29021204
TI  - The fourth pillar: Despite some setbacks in the clinic, immunotherapy has made
      notable progress toward becoming an additional therapeutic option against cancer.

PMID- 29021205
TI  - The ERC: from before then to anniversary celebrations.

PMID- 29021206
TI  - RADX interacts with single-stranded DNA to promote replication fork stability.
AB  - Single-stranded DNA (ssDNA) regions form as an intermediate in many DNA
      associated transactions. Multiple cellular proteins interact with ssDNA via the
      oligonucleotide/oligosaccharide-binding (OB) fold domain. The heterotrimeric,
      multi-OB fold domain-containing Replication Protein A (RPA) complex has an
      essential genome maintenance role, protecting ssDNA regions from nucleolytic
      degradation and providing a recruitment platform for proteins involved in
      responses to replication stress and DNA damage. Here, we identify the
      uncharacterized protein RADX (CXorf57) as an ssDNA-binding factor in human cells.
      RADX binds ssDNA via an N-terminal OB fold cluster, which mediates its
      recruitment to sites of replication stress. Deregulation of RADX expression and
      ssDNA binding leads to enhanced replication fork stalling and degradation, and we
      provide evidence that a balanced interplay between RADX and RPA ssDNA-binding
      activities is critical for avoiding these defects. Our findings establish RADX as
      an important component of cellular pathways that promote DNA replication
      integrity under basal and stressful conditions by means of multiple ssDNA-binding
      proteins.

PMID- 29021207
TI  - Impact of Lifestyle and Metformin Interventions on the Risk of Progression to
      Diabetes and Regression to Normal Glucose Regulation in Overweight or Obese
      People With Impaired Glucose Regulation.
AB  - OBJECTIVE: Both lifestyle and metformin interventions can delay or prevent
      progression to type 2 diabetes mellitus (DM) in people with impaired glucose
      regulation, but there is considerable interindividual variation in the likelihood
      of receiving benefit. Understanding an individual's 3-year risk of progressing to
      DM and regressing to normal glucose regulation (NGR) might facilitate benefit
      based tailored treatment. RESEARCH DESIGN AND METHODS: We used the values of 19
      clinical variables measured at the Diabetes Prevention Program (DPP) baseline
      evaluation and Cox proportional hazards models to assess the 3-year risk of
      progression to DM and regression to NGR separately for DPP lifestyle, metformin,
      and placebo participants who were adherent to the interventions. Lifestyle
      participants who lost >=5% of their initial body weight at 6 months and metformin
      and placebo participants who reported taking >=80% of their prescribed medication
      at the 6-month follow-up were defined as adherent. RESULTS: Eleven of 19 clinical
      variables measured at baseline predicted progression to DM, and 6 of 19 predicted
      regression to NGR. Compared with adherent placebo participants at lowest risk of
      developing diabetes, participants at lowest risk of developing diabetes who
      adhered to a lifestyle intervention had an 8% absolute risk reduction (ARR) of
      developing diabetes and a 35% greater absolute likelihood of reverting to NGR.
      Participants at lowest risk of developing diabetes who adhered to a metformin
      intervention had no reduction in their risk of developing diabetes and a 17%
      greater absolute likelihood of reverting to NGR. Participants at highest risk of
      developing DM who adhered to a lifestyle intervention had a 39% ARR of developing
      diabetes and a 24% greater absolute likelihood of reverting to NGR, whereas those
      who adhered to the metformin intervention had a 25% ARR of developing diabetes
      and an 11% greater absolute likelihood of reverting to NGR. CONCLUSIONS: Unlike
      our previous analyses that sought to explain population risk, these analyses
      evaluate individual risk. The models can be used by overweight and obese adults
      with fasting hyperglycemia and impaired glucose tolerance to facilitate
      personalized decision-making by allowing them to explicitly weigh the benefits
      and feasibility of the lifestyle and metformin interventions.

PMID- 29021210
TI  - New-generation chromoendoscopy may increase confidence in the DISCARD2 study.

PMID- 29021208
TI  - Constitutive role of the Fanconi anemia D2 gene in the replication stress
      response.
AB  - In response to DNA cross-linking damage, the Fanconi anemia (FA) core complex
      activates the FA pathway by monoubiquitinating Fanconi anemia complementation
      group D2 (FANCD2) for the initiation of the nucleolytic processing of the DNA
      cross-links and stabilization of stalled replication forks. Given that all the
      classic FA proteins coordinately monoubiquitinate FANCD2, it is unclear why
      losses of individual classic FA genes yield varying cellular sensitivities to
      cross-linking damage. To address this question, we generated cellular knock-out
      models of FA core complex components and FANCD2 and found that FANCD2-null
      mutants display higher levels of spontaneous chromosomal damage and
      hypersensitivity to replication-blocking lesions than Fanconi anemia
      complementation group L (FANCL)-null mutants, suggesting that FANCD2 provides a
      basal level of DNA protection countering endogenous lesions in the absence of
      monoubiquitination. FANCD2's ubiquitination-independent function is likely
      involved in optimized recruitment of nucleolytic activities for the processing
      and protection of stressed replication forks. Our results reveal that FANCD2 has
      a ubiquitination-independent role in countering endogenous levels of replication
      stress, a function that is critical for the maintenance of genomic stability.

PMID- 29021209
TI  - Transcription profiling suggests that mitochondrial topoisomerase IB acts as a
      topological barrier and regulator of mitochondrial DNA transcription.
AB  - Mitochondrial DNA (mtDNA) is essential for cell viability because it encodes
      subunits of the respiratory chain complexes. Mitochondrial topoisomerase IB
      (TOP1MT) facilitates mtDNA replication by removing DNA topological tensions
      produced during mtDNA transcription, but it appears to be dispensable. To test
      whether cells lacking TOP1MT have aberrant mtDNA transcription, we performed
      mitochondrial transcriptome profiling. To that end, we designed and implemented a
      customized tiling array, which enabled genome-wide, strand-specific, and
      simultaneous detection of all mitochondrial transcripts. Our technique revealed
      that Top1mt KO mouse cells process the mitochondrial transcripts normally but
      that protein-coding mitochondrial transcripts are elevated. Moreover, we found
      discrete long noncoding RNAs produced by H-strand transcription and encompassing
      the noncoding regulatory region of mtDNA in human and murine cells and tissues.
      Of note, these noncoding RNAs were strongly up-regulated in the absence of
      TOP1MT. In contrast, 7S DNA, produced by mtDNA replication, was reduced in the
      Top1mt KO cells. We propose that the long noncoding RNA species in the D-loop
      region are generated by the extension of H-strand transcripts beyond their
      canonical stop site and that TOP1MT acts as a topological barrier and regulator
      for mtDNA transcription and D-loop formation.

PMID- 29021211
TI  - PFMG1 promotes osteoblast differentiation and prevents osteoporotic bone loss.
AB  - Nacre is a widely used mineral medicine that has been reported to have beneficial
      effects in bone remodeling without an increase in inflammation. Water-soluble
      nacre matrix has been demonstrated to be responsible for the effect, yet core
      active ingredients are unknown. Pinctada fucata mantle gene 1 (PFMG1) was first
      discovered in the mantle tissue of Pinctada fucata. The protein has 2 EF-hands, a
      calcium-binding domain. PFMG1 protein can affect the growth of calcium carbonate
      crystals in vitro. Here, we demonstrate that PFMG1 affects cell-cycle
      distribution and promotes preosteoblast proliferation. PFMG1 accelerates
      preosteoblast differentiation and extracellular matrix mineralization. During the
      differentiation process, PFMG1 increases the expression level of osteoblastic
      marker genes and activates the Erk signaling pathway. PFMG1 also accelerates
      calcium crystal aggregation in culture medium and suppresses osteoclast
      formation. Moreover, PFMG1 prevents bone loss caused by ovariectomy. RNA
      sequencing analysis demonstrated that PFMG1 stimulates genes that are associated
      with tissue development and ossification, which indicated new genes that function
      in bone remodeling. Our findings demonstrate the therapeutic potential of PFMG1
      from nacre as a novel medicine for osteoporosis.-Li, L., Wang, P., Hu, K., Wang,
      X., Cai, W., Ai, C., Liu, S., Wang, Z. PFMG1 promotes osteoblast differentiation
      and prevents osteoporotic bone loss.

PMID- 29021212
TI  - Protein SUMOylation modification and its associations with disease.
AB  - SUMOylation, as a post-translational modification, plays essential roles in
      various biological functions including cell growth, migration, cellular responses
      to stress and tumorigenesis. The imbalance of SUMOylation and deSUMOylation has
      been associated with the occurrence and progression of various diseases. Herein,
      we summarize and discuss the signal crosstalk between SUMOylation and
      ubiquitination of proteins, protein SUMOylation relations with several diseases,
      and the identification approaches for SUMOylation site. With the continuous
      development of bioinformatics and mass spectrometry, several accurate and high
      throughput methods have been implemented to explore small ubiquitin-like modifier
      modified substrates and sites, which is helpful for deciphering protein
      SUMOylation-mediated molecular mechanisms of disease.

PMID- 29021213
TI  - Whats, hows and whys of programmed DNA elimination in Tetrahymena.
AB  - Programmed genome rearrangements in ciliates provide fascinating examples of
      flexible epigenetic genome regulations and important insights into the
      interaction between transposable elements (TEs) and host genomes. DNA elimination
      in Tetrahymena thermophila removes approximately 12 000 internal eliminated
      sequences (IESs), which correspond to one-third of the genome, when the somatic
      macronucleus (MAC) differentiates from the germline micronucleus (MIC). More than
      half of the IESs, many of which show high similarity to TEs, are targeted for
      elimination in cis by the small RNA-mediated genome comparison of the MIC to the
      MAC. Other IESs are targeted for elimination in trans by the same small RNAs
      through repetitive sequences. Furthermore, the small RNA-heterochromatin feedback
      loop ensures robust DNA elimination. Here, we review an updated picture of the
      DNA elimination mechanism, discuss the physiological and evolutionary roles of
      DNA elimination, and outline the key questions that remain unanswered.

PMID- 29021214
TI  - Casein kinase II phosphorylation of cyclin F at serine 621 regulates the Lys48
      ubiquitylation E3 ligase activity of the SCF(cyclin F) complex.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that is
      characterized by progressive weakness, paralysis and muscle loss often resulting
      in patient death within 3-5 years of diagnosis. Recently, we identified disease
      linked mutations in the CCNF gene, which encodes the cyclin F protein, in cohorts
      of patients with familial and sporadic ALS and frontotemporal dementia (FTD)
      (Williams KL et al 2016 Nat. Commun.7, 11253. (doi:10.1038/ncomms11253)). Cyclin
      F is a part of a Skp1-Cul-F-box (SCF) E3 ubiquitin-protein ligase complex and is
      responsible for ubiquitylating proteins for degradation by the proteasome. In
      this study, we investigated the phosphorylation status of cyclin F and the effect
      of the serine to glycine substitution at site 621 (S621G) on E3 ligase activity.
      This specific mutation (S621G) was found in a multi-generational Australian
      family with ALS/FTD. We identified seven phosphorylation sites on cyclin F, of
      which five are newly reported including Ser621. These phosphorylation sites were
      mostly identified within the PEST (proline, glutamic acid, serine and threonine)
      sequence located at the C-terminus of cyclin F. Additionally, we determined that
      casein kinase II (CK2) can phosphorylate Ser621 and thereby regulate the E3
      ligase activity of the SCF(cyclin F) complex. Furthermore, the S621G mutation in
      cyclin F prevents phosphorylation by CK2 and confers elevated Lys48
      ubiquitylation activity, a hallmark of ALS/FTD pathology. These findings
      highlight the importance of phosphorylation in regulating the activity of the
      SCF(cyclin F) E3 ligase complex that can affect downstream processes and may lead
      to defective motor neuron development, neuron degeneration and ultimately ALS and
      FTD.

PMID- 29021217
TI  - Impact of Patient-Provider Race, Ethnicity, and Gender Concordance on Cancer
      Screening: Findings from Medical Expenditure Panel Survey.
AB  - Background: Racial and ethnic minorities experience lower rates of cancer
      screening compared with non-Hispanic whites (NHWs). Previous studies evaluating
      the role of patient-provider race, ethnicity, or gender concordance in cancer
      screening have been inconclusive.Methods: In a cross-sectional analysis using the
      Medical Expenditure Panel Survey (MEPS), data from 2003 to 2010 were assessed for
      associations between patient-provider race, ethnicity, and/or gender concordance
      and, screening (American Cancer Society guidelines) for breast, cervical, and
      colorectal cancer. Multivariable logistic analyses were conducted to examine
      associations of interest.Results: Of the 32,041 patient-provider pairs in our
      analysis, more than 60% of the patients were NHW, 15% were non-Hispanic black
      (NHB), and 15% were Hispanic. Overall, patients adherent to cancer screening were
      more likely to be non-Hispanic, better educated, married, wealthier, and
      privately insured. Patient-provider gender discordance was associated with lower
      rates of breast [OR, 0.83; 95% confidence interval (CI), 0.76-0.90], cervical
      (OR, 0.83; 95% CI, 0.76-0.91), and colorectal cancer (OR, 0.84; 95% CI, 0.79
      0.90) screening in all patients. This association was also significant after
      adjusting for racial and/or ethnic concordance. Conversely, among NHWs and NHBs,
      patient-provider racial and/or ethnic concordance was not associated with
      screening. Among Hispanics, patient-provider ethnic discordant pairs had higher
      breast (58% vs. 52%) and colorectal cancer (45% vs. 39%) screening rates compared
      with concordant pairs.Conclusions: Patient-provider gender concordance positively
      affected cancer screening. Patient-provider ethnic concordance was inversely
      associated with receipt of cancer screening among Hispanics. This counter
      intuitive finding requires further study.Impact: Our findings highlight the
      importance of gender concordance in improving cancer screening rates. Cancer
      Epidemiol Biomarkers Prev; 26(12); 1804-11. (c)2017 AACR.

PMID- 29021215
TI  - Dual role of the chromatin-binding factor PHF13 in the pre- and post-integration
      phases of HIV-1 replication.
AB  - Viruses interact with multiple host cell factors. Some of these are required to
      promote viral propagation, others have roles in inhibiting infection. Here, we
      delineate the function of the cellular factor PHF13 (or SPOC1), a putative HIV-1
      restriction factor. Early in the HIV-1 replication cycle PHF13 increased the
      number of integrated proviral copies and the number of infected cells. However,
      after HIV-1 integration, high levels of PHF13 suppressed viral gene expression.
      The antiviral activity of PHF13 is counteracted by the viral accessory protein
      Vpr, which mediates PHF13 degradation. Altogether, the transcriptional master
      regulator and chromatin binding protein PHF13 does not have purely repressive
      effects on HIV-1 replication, but also promotes viral integration. By the
      functional characterization of the dual role of PHF13 during the HIV-1
      replication cycle, we reveal a surprising and intricate mechanism through which
      HIV-1 might regulate the switch from integration to viral gene expression.
      Furthermore, we identify PHF13 as a cellular target specifically degraded by HIV
      1 Vpr.

PMID- 29021216
TI  - Multiple interactions are involved in a highly specific association of the
      Mod(mdg4)-67.2 isoform with the Su(Hw) sites in Drosophila.
AB  - The best-studied Drosophila insulator complex consists of two BTB-containing
      proteins, the Mod(mdg4)-67.2 isoform and CP190, which are recruited to the
      chromatin through interactions with the DNA-binding Su(Hw) protein. It was shown
      previously that Mod(mdg4)-67.2 is critical for the enhancer-blocking activity of
      the Su(Hw) insulators and it differs from more than 30 other Mod(mdg4) isoforms
      by the C-terminal domain required for a specific interaction with Su(Hw) only.
      The mechanism of the highly specific association between Mod(mdg4)-67.2 and
      Su(Hw) is not well understood. Therefore, we have performed a detailed analysis
      of domains involved in the interaction of Mod(mdg4)-67.2 with Su(Hw) and CP190.
      We found that the N-terminal region of Su(Hw) interacts with the glutamine-rich
      domain common to all the Mod(mdg4) isoforms. The unique C-terminal part of
      Mod(mdg4)-67.2 contains the Su(Hw)-interacting domain and the FLYWCH domain that
      facilitates a specific association between Mod(mdg4)-67.2 and the CP190/Su(Hw)
      complex. Finally, interaction between the BTB domain of Mod(mdg4)-67.2 and the M
      domain of CP190 has been demonstrated. By using transgenic lines expressing
      different protein variants, we have shown that all the newly identified
      interactions are to a greater or lesser extent redundant, which increases the
      reliability in the formation of the protein complexes.

PMID- 29021218
TI  - Transcriptomic Analysis of Octanoic Acid Response in Drosophila sechellia Using
      RNA-Sequencing.
AB  - The dietary specialist fruit fly Drosophila sechellia has evolved to specialize
      on the toxic fruit of its host plant Morinda citrifolia Toxicity of Morinda fruit
      is primarily due to high levels of octanoic acid (OA). Using RNA interference
      (RNAi), prior work found that knockdown of Osiris family genes Osiris 6 (Osi6),
      Osi7, and Osi8 led to increased susceptibility to OA in adult D. melanogaster
      flies, likely representing genes underlying a Quantitative Trait Locus (QTL) for
      OA resistance in D. sechellia While genes in this major effect locus are
      beginning to be revealed, prior work has shown at least five regions of the
      genome contribute to OA resistance. Here, we identify new candidate OA resistance
      genes by performing differential gene expression analysis using RNA-sequencing
      (RNA-seq) on control and OA-exposed D. sechellia flies. We found 104
      significantly differentially expressed genes with annotated orthologs in D.
      melanogaster, including six Osiris gene family members, consistent with previous
      functional studies and gene expression analyses. Gene ontology (GO) term
      enrichment showed significant enrichment for cuticle development in upregulated
      genes and significant enrichment of immune and defense responses in downregulated
      genes, suggesting important aspects of the physiology of D. sechellia that may
      play a role in OA resistance. In addition, we identified five candidate OA
      resistance genes that potentially underlie QTL peaks outside of the major effect
      region, representing promising new candidate genes for future functional studies.

PMID- 29021220
TI  - An apicosome initiates self-organizing morphogenesis of human pluripotent stem
      cells.
AB  - Human pluripotent stem cells (hPSCs) self-organize into apicobasally polarized
      cysts, reminiscent of the lumenal epiblast stage, providing a model to explore
      key morphogenic processes in early human embryos. Here, we show that apical
      polarization begins on the interior of single hPSCs through the dynamic formation
      of a highly organized perinuclear apicosome structure. The membrane surrounding
      the apicosome is enriched in apical markers and displays microvilli and a primary
      cilium; its lumenal space is rich in Ca2+ Time-lapse imaging of isolated hPSCs
      reveals that the apicosome forms de novo in interphase, retains its structure
      during mitosis, is asymmetrically inherited after mitosis, and relocates to the
      recently formed cytokinetic plane, where it establishes a fully polarized lumen.
      In a multicellular aggregate of hPSCs, intracellular apicosomes from multiple
      cells are trafficked to generate a common lumenal cavity. Thus, the apicosome is
      a unique preassembled apical structure that can be rapidly used in single or
      clustered hPSCs to initiate self-organized apical polarization and lumenogenesis.

PMID- 29021222
TI  - The perivascular pathways for influx of cerebrospinal fluid are most efficient in
      the midbrain.
AB  - Although there are no conventional lymphatic vessels in the brain, fluid and
      solutes drain along basement membranes (BMs) of cerebral capillaries and arteries
      towards the subarachnoid space and cervical lymph nodes. Convective
      influx/glymphatic entry of the cerebrospinal fluid (CSF) into the brain
      parenchyma occurs along the pial-glial BMs of arteries. This project tested the
      hypotheses that pial-glial BM of arteries are thicker in the midbrain, allowing
      more glymphatic entry of CSF. The in vivo MRI and PET images were obtained from a
      4.2-year-old dog, whereas the post-mortem electron microscopy was performed in a
      12-year-old dog. We demonstrated a significant increase in the thickness of the
      pial-glial BM in the midbrain compared with the same BM in different regions of
      the brain and an increase in the convective influx of fluid from the subarachnoid
      space. These results are highly significant for the intrathecal drug delivery
      into the brain, indicating that the midbrain is better equipped for convective
      influx/glymphatic entry of the CSF.

PMID- 29021221
TI  - Cancer-associated fibroblasts promote directional cancer cell migration by
      aligning fibronectin.
AB  - Cancer-associated fibroblasts (CAFs) are major components of the carcinoma
      microenvironment that promote tumor progression. However, the mechanisms by which
      CAFs regulate cancer cell migration are poorly understood. In this study, we show
      that fibronectin (Fn) assembled by CAFs mediates CAF-cancer cell association and
      directional migration. Compared with normal fibroblasts, CAFs produce an Fn-rich
      extracellular matrix with anisotropic fiber orientation, which guides the cancer
      cells to migrate directionally. CAFs align the Fn matrix by increasing nonmuscle
      myosin II- and platelet-derived growth factor receptor alpha-mediated
      contractility and traction forces, which are transduced to Fn through alpha5beta1
      integrin. We further show that prostate cancer cells use alphav integrin to
      migrate efficiently and directionally on CAF-derived matrices. We demonstrate
      that aligned Fn is a prominent feature of invasion sites in human prostatic and
      pancreatic carcinoma samples. Collectively, we present a new mechanism by which
      CAFs organize the Fn matrix and promote directional cancer cell migration.

PMID- 29021219
TI  - Stochastic Community Assembly: Does It Matter in Microbial Ecology?
AB  - Understanding the mechanisms controlling community diversity, functions,
      succession, and biogeography is a central, but poorly understood, topic in
      ecology, particularly in microbial ecology. Although stochastic processes are
      believed to play nonnegligible roles in shaping community structure, their
      importance relative to deterministic processes is hotly debated. The importance
      of ecological stochasticity in shaping microbial community structure is far less
      appreciated. Some of the main reasons for such heavy debates are the difficulty
      in defining stochasticity and the diverse methods used for delineating
      stochasticity. Here, we provide a critical review and synthesis of data from the
      most recent studies on stochastic community assembly in microbial ecology. We
      then describe both stochastic and deterministic components embedded in various
      ecological processes, including selection, dispersal, diversification, and drift.
      We also describe different approaches for inferring stochasticity from
      observational diversity patterns and highlight experimental approaches for
      delineating ecological stochasticity in microbial communities. In addition, we
      highlight research challenges, gaps, and future directions for microbial
      community assembly research.

PMID- 29021226
TI  - Attenuation of accelerated renal cystogenesis in Pkd1 mice by renin-angiotensin
      system blockade.
AB  - The intrarenal renin angiotensin system (RAS) is activated in polycystic kidney
      disease. We have recently shown in the Pkd1 mouse that Gen 2 antisense
      oligonucleotide (ASO), which suppresses angiotensinogen (Agt) synthesis, is
      efficacious in slowing kidney cyst formation compared with lisinopril. The aim of
      this current study was to determine 1) if unilateral nephrectomy accelerates
      cystogenesis in Pkd1 mice (as previously shown in cilia knockout mice) and 2)
      whether Agt ASO can slow the progression in this accelerated cystic mouse model.
      Adult Pkd1 conditional floxed allele mice expressing cre were administered
      tamoxifen, resulting in global knockout of Pkd1. Three weeks after tamoxifen
      injection, mice underwent left unilateral nephrectomy. Mice were then treated
      with Agt ASO (75 mg/kg per week) or aliskiren (20 mg/kg per day)+Agt ASO or
      control for 8 wk. Unilateral nephrectomy accelerated kidney cyst formation
      compared with nonnephrectomized mice. Both Agt ASO and Aliskiren+Agt ASO
      treatments significantly reduced plasma and urinary Agt levels. Blood pressure
      was lowest in Aliskiren+Agt ASO mice among all treatment groups, and the control
      group had the highest blood pressure. All mice developed significant kidney cysts
      at 8 wk after nephrectomy, but Agt ASO and Aliskiren+Agt ASO groups had fewer
      kidney cysts than controls. Renal pAkt, pS6 levels, and apoptosis were
      significantly suppressed in those receiving Agt ASO compared with controls. These
      results indicate that suppressing Agt using an ASO slowed the progression of
      accelerated cystic kidney disease induced by unilateral nephrectomy in Pkd1 mice
      by suppressing intrarenal RAS, mammalian target of rapamycin pathway, and cell
      proliferation.

PMID- 29021225
TI  - ATP induces PAD4 in renal proximal tubule cells via P2X7 receptor activation to
      exacerbate ischemic AKI.
AB  - We previously demonstrated that renal tubular peptidylarginine deiminase-4 (PAD4)
      is induced after ischemia-reperfusion (IR) injury and this induction of PAD4
      exacerbates ischemic acute kidney injury (AKI) by promoting renal tubular
      inflammation and neutrophil infiltration. However, the mechanisms of renal
      tubular PAD4 induction after IR remain unknown. Here, we tested the hypothesis
      that ATP, a proinflammatory danger-associated molecular pattern (DAMP) ligand
      released from necrotic cells after IR injury, induces renal tubular PAD4 and
      exacerbates ischemic AKI via P2 purinergic receptor activation. ATP as well as
      ATPgammaS (a nonmetabolizable ATP analog) induced PAD4 mRNA, protein, and
      activity in human and mouse renal proximal tubule cells. Supporting the
      hypothesis that ATP induces renal tubular PAD4 via P2X7 receptor activation,
      A804598 (a selective P2X7 receptor antagonist) blocked the ATP-mediated induction
      of renal tubular PAD4 whereas BzATP (a selective P2X7 receptor agonist) mimicked
      the effects of ATP by inducing renal tubular PAD4 expression and activity.
      Moreover, ATP-mediated calcium influx in renal proximal tubule cells was blocked
      by A804598 and was mimicked by BzATP. P2X7 activation by BzATP also induced PAD4
      expression and activity in mouse kidney in vivo. Finally, supporting a critical
      role for PAD4 in P2X7-mediated exacerbation of renal injury, BzATP exacerbated
      ischemic AKI in PAD4 wild-type mice but not in PAD4-deficient mice. Taken
      together, our studies show that ATP induces renal tubular PAD4 via P2X7 receptor
      activation to exacerbate renal tubular inflammation and injury after IR.

PMID- 29021224
TI  - A Violaxanthin Deepoxidase Interacts with a Viral Suppressor of RNA Silencing to
      Inhibit Virus Amplification.
AB  - RNA silencing plays a critical role against viral infection. To counteract this
      antiviral silencing, viruses have evolved various RNA silencing suppressors.
      Meanwhile, plants have evolved counter-counter defense strategies against RNA
      silencing suppression (RSS). In this study, the violaxanthin deepoxidase protein
      of maize (Zea mays), ZmVDE, was shown to interact specifically with the helper
      component-proteinase (HC-Pro; a viral RNA silencing suppressor) of Sugarcane
      mosaic virus (SCMV) via its mature protein region by yeast two-hybrid assay,
      which was confirmed by coimmunoprecipitation in Nicotiana benthamiana cells. It
      was demonstrated that amino acids 101 to 460 in HC-Pro and the amino acid
      glutamine-292 in ZmVDE mature protein were essential for this interaction. The
      mRNA levels of ZmVDE were down-regulated 75% to 65% at an early stage of SCMV
      infection. Interestingly, ZmVDE, which normally localized in the chloroplasts and
      cytoplasm, could relocalize to HC-Pro-containing aggregate bodies in the presence
      of HC-Pro alone or SCMV infection. In addition, ZmVDE could attenuate the RSS
      activity of HC-Pro in a specific protein interaction-dependent manner.
      Subsequently, transient silencing of the ZmVDE gene facilitated SCMV RNA and coat
      protein accumulation. Taken together, our results suggest that ZmVDE interacts
      with SCMV HC-Pro and attenuates its RSS activity, contributing to decreased SCMV
      accumulation. This study demonstrates that a host factor can be involved in
      secondary defense responses against viral infection in monocot plants.

PMID- 29021227
TI  - Physiological regulation of the epithelial Na+ channel by casein kinase II.
AB  - epithelial Na+ channel, ENaC, is the final arbiter of sodium excretion in the
      kidneys. As such, discretionary control of ENaC by hormones is critical to the
      fine-tuning of electrolyte and water excretion and, consequently, blood pressure.
      Casein kinase 2 (CK2) phosphorylates ENaC. Phosphorylation by CK2 is necessary
      for normal ENaC activity. We tested the physiological importance of CK2
      regulation of ENaC as the degree to which ENaC activity is dependent on CK2
      phosphorylation in the living organism is unknown. This was addressed using patch
      clamp analysis of ENaC in completely split-open collecting ducts and whole animal
      physiological studies of sodium excretion in mice. We also used ENaC-harboring
      CK2 phosphorylation site mutations to elaborate the mechanism. We found that ENaC
      activity in ex vivo preparations of murine collecting duct had a significant
      decrease in activity in response to selective antagonism of CK2. In whole animal
      experiments selective antagonism of CK2 caused a natriuresis similar to benzamil,
      but not additive to benzamil, suggesting an ENaC-dependent mechanism. Regulation
      of ENaC by CK2 was abolished by mutation of the canonical CK2 phosphorylation
      sites in beta and gamma ENaC. Together, these results demonstrate that the
      appropriate regulation of ENaC by CK2 is necessary for the normal physiological
      role played by this key renal ion channel in the fine-tuning of sodium excretion.

PMID- 29021223
TI  - Peroxisome Function, Biogenesis, and Dynamics in Plants.

PMID- 29021228
TI  - Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell
      transplant: a PIDTC natural history study.
AB  - The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children
      with severe combined immunodeficiency (SCID) to a prospective natural history
      study. We analyzed patients treated with allogeneic hematopoietic cell
      transplantation (HCT) from 2010 to 2014, including 68 patients with typical SCID
      and 32 with leaky SCID, Omenn syndrome, or reticular dysgenesis. Most (59%)
      patients were diagnosed by newborn screening or family history. The 2-year
      overall survival was 90%, but was 95% for those who were infection-free at HCT vs
      81% for those with active infection (P = .009). Other factors, including the
      diagnosis of typical vs leaky SCID/Omenn syndrome, diagnosis via family history
      or newborn screening, use of preparative chemotherapy, or the type of donor used,
      did not impact survival. Although 1-year post-HCT median CD4 counts and freedom
      from IV immunoglobulin were improved after the use of preparative chemotherapy,
      other immunologic reconstitution parameters were not affected, and the potential
      for late sequelae in extremely young infants requires additional evaluation.
      After a T-cell-replete graft, landmark analysis at day +100 post-HCT revealed
      that CD3 < 300 cells/MUL, CD8 < 50 cells/MUL, CD45RA < 10%, or a restricted Vbeta
      T-cell receptor repertoire (<13 of 24 families) were associated with the need for
      a second HCT or death. In the modern era, active infection continues to pose the
      greatest threat to survival for SCID patients. Although newborn screening has
      been effective in diagnosing SCID patients early in life, there is an urgent need
      to identify validated approaches through prospective trials to ensure that
      patients proceed to HCT infection free. The trial was registered at
      www.clinicaltrials.gov as #NCT01186913.

PMID- 29021230
TI  - Gemtuzumab ozogamicin for acute myeloid leukemia.
AB  - On 1 September 2017, the US Food and Drug Administration (FDA) approved
      gemtuzumab ozogamicin (GO) for the treatment of adults with newly diagnosed CD33+
      acute myeloid leukemia and for patients aged >=2 years with CD33+ acute myeloid
      leukemia who have experienced a relapse or who have not responded to initial
      treatment. This signals a new chapter in the long and unusual story of GO, which
      was the first antibody-drug conjugate approved for human use by the FDA.

PMID- 29021231
TI  - Deletion of BMP6 worsens the phenotype of HJV-deficient mice and attenuates
      hepcidin levels reached after LPS challenge.
AB  - Lack of either bone morphogenetic protein 6 (BMP6) or the BMP coreceptor
      hemojuvelin (HJV) in mice leads to a similar phenotype with hepcidin
      insufficiency, hepatic iron loading, and extrahepatic iron accumulation in males.
      This is consistent with the current views that HJV is a coreceptor for BMP6 in
      hepatocytes. To determine whether BMP6 and HJV may also signal to hepcidin
      independently of each other, we intercrossed Hjv-/- and Bmp6-/- mice and compared
      the phenotype of animals of the F2 progeny. Loss of Bmp6 further repressed Smad
      signaling and hepcidin expression in the liver of Hjv-/- mice of both sexes, and
      led to iron accumulation in the pancreas and the heart of females. These data
      suggest that, in Hjv-/- females, Bmp6 can provide a signal adequate to maintain
      hepcidin to a level sufficient to avoid extrahepatic iron loading. We also
      examined the impact of Bmp6 and/or Hjv deletion on the regulation of hepcidin by
      inflammation. Our data show that lack of 1 or both molecules does not prevent
      induction of hepcidin by lipopolysaccharide (LPS). However, BMP/Smad signaling in
      unchallenged animals is determinant for the level of hepcidin reached after
      stimulation, which is consistent with a synergy between interleukin 6/STAT3 and
      BMP/SMAD signaling in regulating hepcidin during inflammation.

PMID- 29021233
TI  - Divergent Activity of the Pseudogene PTENP1 in ER-Positive and Negative Breast
      Cancer.
AB  - Transcripts derived from the PTEN pseudogene (PTENP1) function as decoys to
      adsorb miRNAs targeting the PTEN tumor suppressor for degradation, and PTENP1
      upregulation is known to inhibit growth in preclinical cancer models. Here,
      PTENP1 3'UTR transduction influences PTEN, AKT/mTOR signaling, and tumor
      progression in estrogen receptor (ER)-positive and -negative breast cancer cells.
      PTENP1 upregulation decreases PTEN gene expression in the ER-positive MCF7 and
      T47D human breast carcinoma cells and accelerates MCF7 tumor growth in vivo Of
      note, PTENP1 transduction significantly decreases ERalpha (ESR1) mRNA and protein
      levels in MCF7 xenografts with a concomitant increase in hsa-miR-26a, a miRNA
      known to target ESR1 In the ER-negative MDA-MB-231 and C3HBA breast cancer cells,
      upregulation of PTENP1 increases PTEN gene expression with no influence on hsa
      miR-26a, ESR1, or ERalpha expression. While PTENP1 transduction did not influence
      the growth rate of human MDA-MB-231 xenografts, PTENP1 upregulation profoundly
      reduces its metastatic propensity. Furthermore, PTENP1 significantly inhibits the
      growth rate of ER-negative C3HBA murine breast cancer xenografts. PTENP1
      transduction had no influence on doxorubicin cytotoxicity in ER-positive MCF7
      cells but an increase in doxorubicin sensitivity was observed in the ER-negative
      MDA-MB-231 cells. In summary, while PTENP1 upregulation decreased PTEN transcript
      levels and stimulated the growth of ER-positive breast cancers, increased PTEN
      transcript levels and inhibited tumor progression was observed in the ER-negative
      cells.Implications: This report highlights the profound biological activity of
      PTENP1 in breast cancer, which is dictated by the hormone receptor status. Mol
      Cancer Res; 16(1); 78-89. (c)2017 AACR.

PMID- 29021229
TI  - In vivo-generated thrombin and plasmin do not activate the complement system in
      baboons.
AB  - Sepsis concurrently activates both coagulation and complement systems. Although
      complement activation by bacteria is well documented, work in mice and in vitro
      suggests that coagulation proteases can directly cleave complement proteins. We
      aimed to determine whether generation of coagulation proteases in vivo can
      activate the complement cascade in 2 highly coagulopathic models. We compared
      temporal changes in activation biomarkers of coagulation (thrombin-antithrombin
      [TAT]), fibrinolysis (plasmin-antiplasmin [PAP]), and complement (C3b, C5a, C5b
      9) in baboons infused with factor Xa (FXa) and phospholipids
      (FXa/phosphatidylcholine-phosphatidylserine [PCPS]) vs LD100 Escherichia coli We
      found that, albeit with different timing, both FXa/PCPS and E coli infusion led
      to robust thrombin and plasmin generation. Conversely, only E coli challenge
      activated the complement system, reaching a maximum at 2 hours postchallenge
      during the peaks of lipopolysaccharide and bacteremia but not of TAT and PAP.
      Despite inducing a strong burst of thrombin and plasmin, FXa/PCPS infusion did
      not produce measurable levels of complement activation in vivo. Similarly, ex
      vivo incubation of baboon serum with thrombin, plasmin, or FXa did not show
      noticeable complement cleavage unless supraphysiologic amounts of enzymes were
      used. Our results suggest that in vivo-generated thrombin and plasmin do not
      directly activate the complement in nonhuman primates.

PMID- 29021232
TI  - PKCepsilon Controls Mitotic Progression by Regulating Centrosome Migration and
      Mitotic Spindle Assembly.
AB  - To form a proper mitotic spindle, centrosomes must be duplicated and driven
      poleward in a timely and controlled fashion. Improper timing of centrosome
      separation and errors in mitotic spindle assembly may lead to chromosome
      instability, a hallmark of cancer. Protein kinase C epsilon (PKCepsilon) has
      recently emerged as a regulator of several cell-cycle processes associated with
      the resolution of mitotic catenation during the metaphase-anaphase transition and
      in regulating the abscission checkpoint. However, an engagement of PKCepsilon in
      earlier (pre)mitotic events has not been addressed. Here, we now establish that
      PKCepsilon controls prophase-to-metaphase progression by coordinating centrosome
      migration and mitotic spindle assembly in transformed cells. This control is
      exerted through cytoplasmic dynein function. Importantly, it is also demonstrated
      that the PKCepsilon dependency of mitotic spindle organization is correlated with
      the nonfunctionality of the TOPO2A-dependent G2 checkpoint, a characteristic of
      many transformed cells. Thus, PKCepsilon appears to become specifically engaged
      in a programme of controls that are required to support cell-cycle progression in
      transformed cells, advocating for PKCepsilon as a potential cancer therapeutic
      target.Implications: The close relationship between PKCepsilon dependency for
      mitotic spindle organization and the nonfunctionality of the TOPO2A-dependent G2
      checkpoint, a hallmark of transformed cells, strongly suggests PKCepsilon as a
      therapeutic target in cancer. Mol Cancer Res; 16(1); 3-15. (c)2017 AACR.

PMID- 29021234
TI  - Speed and Safety in Drug Approval and Commercialization.

PMID- 29021236
TI  - How useful is PET/CT in the evaluation of fever/inflammation of unknown origin?
      Comment on the article by Schonau et al.

PMID- 29021235
TI  - Oral Analgesics Utilization for Children With Musculoskeletal Injury (OUCH
      Trial): An RCT.
AB  - BACKGROUND: Musculoskeletal injuries (MSK-Is) are a common and painful condition
      among children that remains poorly treated in the emergency department (ED). We
      aimed to test the efficacy of a combination of an anti-inflammatory drug with an
      opioid for pain management of MSK-I in children presenting to the ED. METHODS: In
      this randomized, double-blinded, placebo-controlled trial, we enrolled children
      between 6 and 17 years presenting to the ED with an MSK-I and a pain score >29 mm
      on the visual analog scale (VAS). Participants were randomly assigned to oral
      morphine (0.2 mg/kg) + ibuprofen (10 mg/kg) (morphine + ibuprofen) or morphine
      (0.2 mg/kg) + placebo of ibuprofen or ibuprofen (10 mg/kg) + placebo of morphine.
      Primary outcome was children with VAS pain score <30 mm at 60 minutes
      postmedication administration. RESULTS: A total of 501 participants were enrolled
      and 456 were included in primary analyses (morphine + ibuprofen = 177; morphine =
      188; ibuprofen = 91). Only 29.9% (morphine + ibuprofen), 29.3% (morphine), and
      33.0% (ibuprofen) of participants achieved the primary outcome (P = .81). Mean
      VAS pain reduction at 60 minutes were -18.7 (95% confidence interval [CI]: -21.9
      to -16.6) (morphine + ibuprofen), -17.0 (95% CI: -20.0 to -13.9) (morphine), 
      18.6 (95% CI: -22.9 to -14.2) (ibuprofen) (P = .69). Children in the morphine +
      ibuprofen group (P < .001) and in the morphine group (P < .001) experienced more
      side effects than those in the ibuprofen group. No serious adverse event was
      reported. CONCLUSIONS: Combination of morphine with ibuprofen did not provide
      adequate pain relief for children with MSK-I in the ED. None of the study
      medication provided an optimal pain management because most of children did not
      reach a mild pain score (NCT02064894).

PMID- 29021237
TI  - Recommendations for collaborative paediatric research including biobanking in
      Europe: a Single Hub and Access point for paediatric Rheumatology in Europe
      (SHARE) initiative.
AB  - Innovative research in childhood rheumatic diseases mandates international
      collaborations. However, researchers struggle with significant regulatory
      heterogeneity; an enabling European Union (EU)-wide framework is missing. The
      aims of the study were to systematically review the evidence for best practice
      and to establish recommendations for collaborative research. The Paediatric
      Rheumatology European Single Hub and Access point for paediatric Rheumatology in
      Europe (SHARE) project enabled a scoping review and expert discussion, which then
      informed the systematic literature review. Published evidence was synthesised;
      recommendations were drafted. An iterative review process and consultations with
      Ethics Committees and European experts for ethical and legal aspects of
      paediatric research refined the recommendations. SHARE experts and patient
      representatives vetted the proposed recommendations at a consensus meeting using
      Nominal Group Technique. Agreement of 80% was mandatory for inclusion. The
      systematic literature review returned 1319 records. A total of 223 full-text
      publications plus 22 international normative documents were reviewed; 85
      publications and 16 normative documents were included. A total of 21
      recommendations were established including general principles (1-3), ethics (4
      7), paediatric principles (8 and 9), consent to paediatric research (10-14),
      paediatric databank and biobank (15 and 16), sharing of data and samples (17-19),
      and commercialisation and third parties (20 and 21). The refined recommendations
      resulted in an agreement of >80% for all recommendations. The SHARE initiative
      established the first recommendations for Paediatric Rheumatology collaborative
      research across borders in Europe. These provide strong support for an urgently
      needed European framework and evidence-based guidance for its implementation.
      Such changes will promote research in children with rheumatic diseases.

PMID- 29021238
TI  - Asy2/Mer2: an evolutionarily conserved mediator of meiotic recombination,
      pairing, and global chromosome compaction.
AB  - Meiosis is the cellular program by which a diploid cell gives rise to haploid
      gametes for sexual reproduction. Meiotic progression depends on tight physical
      and functional coupling of recombination steps at the DNA level with specific
      organizational features of meiotic-prophase chromosomes. The present study
      reveals that every step of this coupling is mediated by a single molecule:
      Asy2/Mer2. We show that Mer2, identified so far only in budding and fission
      yeasts, is in fact evolutionarily conserved from fungi (Mer2/Rec15/Asy2/Bad42) to
      plants (PRD3/PAIR1) and mammals (IHO1). In yeasts, Mer2 mediates assembly of
      recombination-initiation complexes and double-strand breaks (DSBs). This role is
      conserved in the fungus Sordaria However, functional analysis of 13 mer2 mutants
      and successive localization of Mer2 to axis, synaptonemal complex (SC), and
      chromatin revealed, in addition, three further important functions. First, after
      DSB formation, Mer2 is required for pairing by mediating homolog spatial
      juxtaposition, with implications for crossover (CO) patterning/interference.
      Second, Mer2 participates in the transfer/maintenance and release of
      recombination complexes to/from the SC central region. Third, after completion of
      recombination, potentially dependent on SUMOylation, Mer2 mediates global
      chromosome compaction and post-recombination chiasma development. Thus, beyond
      its role as a recombinosome-axis/SC linker molecule, Mer2 has important functions
      in relation to basic chromosome structure.

PMID- 29021239
TI  - An RNA-binding protein, Qki5, regulates embryonic neural stem cells through pre
      mRNA processing in cell adhesion signaling.
AB  - Cell type-specific transcriptomes are enabled by the action of multiple
      regulators, which are frequently expressed within restricted tissue regions. In
      the present study, we identify one such regulator, Quaking 5 (Qki5), as an RNA
      binding protein (RNABP) that is expressed in early embryonic neural stem cells
      and subsequently down-regulated during neurogenesis. mRNA sequencing analysis in
      neural stem cell culture indicates that Qki proteins play supporting roles in the
      neural stem cell transcriptome and various forms of mRNA processing that may
      result from regionally restricted expression and subcellular localization. Also,
      our in utero electroporation gain-of-function study suggests that the nuclear
      type Qki isoform Qki5 supports the neural stem cell state. We next performed in
      vivo transcriptome-wide protein-RNA interaction mapping to search for direct
      targets of Qki5 and elucidate how Qki5 regulates neural stem cell function.
      Combined with our transcriptome analysis, this mapping analysis yielded a bona
      fide map of Qki5-RNA interaction at single-nucleotide resolution, the
      identification of 892 Qki5 direct target genes, and an accurate Qki5-dependent
      alternative splicing rule in the developing brain. Last, our target gene list
      provides the first compelling evidence that Qki5 is associated with specific
      biological events; namely, cell-cell adhesion. This prediction was confirmed by
      histological analysis of mice in which Qki proteins were genetically ablated,
      which revealed disruption of the apical surface of the lateral wall in the
      developing brain. These data collectively indicate that Qki5 regulates
      communication between neural stem cells by mediating numerous RNA processing
      events and suggest new links between splicing regulation and neural stem cell
      states.

PMID- 29021240
TI  - Integrative genome analysis of somatic p53 mutant osteosarcomas identifies Ets2
      dependent regulation of small nucleolar RNAs by mutant p53 protein.
AB  - TP53 is the most frequently mutated gene in human cancer. Many mutant p53
      proteins exert oncogenic gain-of-function (GOF) properties that contribute to
      metastasis, but the mechanisms mediating these functions remain poorly defined in
      vivo. To elucidate how mutant p53 GOF drives metastasis, we developed a traceable
      somatic osteosarcoma mouse model that is initiated with either a single p53
      mutation (p53R172H) or p53 loss in osteoblasts. Our study confirmed that p53
      mutant mice developed osteosarcomas with increased metastasis as compared with
      p53-null mice. Comprehensive transcriptome RNA sequencing (RNA-seq) analysis of
      16 tumors identified a cluster of small nucleolar RNAs (snoRNAs) that are highly
      up-regulated in p53 mutant tumors. Regulatory element analysis of these
      deregulated snoRNA genes identified strong enrichment of a common Ets2
      transcription factor-binding site. Homozygous deletion of Ets2 in p53 mutant mice
      resulted in strong down-regulation of snoRNAs and reversed the prometastatic
      phenotype of mutant p53 but had no effect on osteosarcoma development, which
      remained 100% penetrant. In summary, our studies identify Ets2 inhibition as a
      potential therapeutic vulnerability in p53 mutant osteosarcomas.

PMID- 29021241
TI  - Two distinct transcription termination modes dictated by promoters.
AB  - Transcription termination determines the ends of transcriptional units and
      thereby ensures the integrity of the transcriptome and faithful gene regulation.
      Studies in yeast and human cells have identified the exoribonuclease XRN2 as a
      key termination factor for protein-coding genes. Here we performed a genome-wide
      investigation of RNA polymerase II (Pol II) transcription termination in XRN2
      deficient Caenorhabditis elegans and observed two distinct modes of termination.
      Although a subset of genes requires XRN2, termination of other genes appears both
      independent of, and refractory to, XRN2. XRN2 independence is not merely a
      consequence of failure to recruit XRN2, since XRN2 is present on-and promotes Pol
      II accumulation near the polyadenylation sites of-both gene classes.
      Unexpectedly, promoters instruct the choice of termination mode, but XRN2
      independent termination additionally requires a compatible region downstream from
      the 3' end cleavage site. Hence, different termination mechanisms may work with
      different configurations of Pol II complexes dictated by promoters.

PMID- 29021244
TI  - Tackling concussion in professional rugby union: a case-control study of tackle
      based risk factors and recommendations for primary prevention.
AB  - BACKGROUND/AIM: Concussion, the most common injury in professional rugby union,
      occurs most commonly during the tackle. Thus, we investigated the association
      between tackle characteristics and concussion. METHODS: 182 video clips of
      tackles leading to clinically diagnosed concussion and 4619 tackles that did not
      were coded across three professional rugby union competitions. A variable
      selection process was undertaken to identify the most important variables for
      interpretation. A multivariate generalised linear model was used to model the
      association between retained variables and concussion risk. Magnitude-based
      inferences provided an interpretation of the real-world relevance of the
      outcomes. RESULTS: The four retained variables were: accelerating player, tackler
      speed, head contact type and tackle type. Overall, 70% of concussions occurred to
      the tackler and 30% to the ball carrier. There was a higher risk of concussion if
      the tackler accelerated into the tackle (OR: 2.49, 95% CI 1.70 to 3.64) or the
      tackler was moving at high speed (OR: 2.64, 95% CI 1.92 to 3.63). Head contact
      with the opposing player's head (OR: 39.9, 95% CI 22.2 to 71.1) resulted in a
      substantially greater risk of concussion compared with all other head contact
      locations. CONCLUSIONS: Interventions that reduce the speed and acceleration of
      the tackler and reduce exposure to head-to-head contact would likely reduce
      concussion risk in professional rugby union.

PMID- 29021246
TI  - Zombie reviews taking over the PROSPERO systematic review registry. It's time to
      fight back!

PMID- 29021245
TI  - Time out: ethical reflections on medical disqualification of athletes in the
      context of mandated pre-participation cardiac screening.

PMID- 29021243
TI  - Zucchini-dependent piRNA processing is triggered by recruitment to the
      cytoplasmic processing machinery.
AB  - The piRNA pathway represses transposable elements in the gonads and thereby plays
      a vital role in protecting the integrity of germline genomes of animals. Mature
      piRNAs are processed from longer transcripts, piRNA precursors (pre-piRNAs). In
      Drosophila, processing of pre-piRNAs is initiated by piRNA-guided Slicer cleavage
      or the endonuclease Zucchini (Zuc). As Zuc does not have any sequence or
      structure preferences in vitro, it is not known how piRNA precursors are selected
      and channeled into the Zuc-dependent processing pathway. We show that a
      heterologous RNA that lacks complementary piRNAs is processed into piRNAs upon
      recruitment of several piRNA pathway factors. This processing requires Zuc and
      the helicase Armitage (Armi). Aubergine (Aub), Argonaute 3 (Ago3), and components
      of the nuclear RDC complex, which are required for normal piRNA biogenesis in
      germ cells, are dispensable. Our approach allows discrimination of proteins
      involved in the transcription and export of piRNA precursors from components
      required for the cytoplasmic processing steps. piRNA processing correlates with
      localization of the substrate RNA to nuage, a distinct membraneless cytoplasmic
      compartment, which surrounds the nucleus of germ cells, suggesting that
      sequestration of RNA to this subcellular compartment is both necessary and
      sufficient for selecting piRNA biogenesis substrates.

PMID- 29021247
TI  - Why we should focus on the burden of injuries and illnesses, not just their
      incidence.

PMID- 29021248
TI  - Live attenuated influenza vaccine for children.
AB  - For many years, the UK seasonal influenza vaccination programme has been offered
      to people at higher risk from the complications of influenza infection, including
      those aged over 65 years and anyone aged over 6 months who is in a clinical risk
      group.1 In 2012, the Joint Committee on Vaccination and Immunisation (JCVI)
      recommended extending seasonal influenza vaccination to children aged 2-16 years
      who are not in a clinical risk group.2 In contrast to the vaccination programme
      for adults, which uses an injectable inactivated influenza vaccine, children are
      being offered a live attenuated influenza vaccine (LAIV) that is administered
      intranasally.2 Here, we consider the evidence for the use of the intranasal
      influenza vaccine for children who are not in a clinical risk group.

PMID- 29021249
TI  - Prescribing PPIs.
AB  - Proton pump inhibitors (PPIs) are widely prescribed and many people remain on
      them for years. In some, there may be good justification for long-term use; for
      example, in those with oesophageal stricture, Barrett's oesophagus or a history
      of a bleeding gastrointestinal ulcer, or to provide gastroprotection in those at
      high risk of gastrointestinal complications from taking NSAIDs. However, PPIs are
      often not used in line with clinical guidelines.1,2 In addition, there are
      concerns that many people take them for long periods to manage less serious
      conditions (e.g. indigestion) and may prefer taking them to addressing factors
      such as diet, obesity or alcohol that may be contributing to their symptoms.
      Although PPIs are well-tolerated, there is increasing evidence that they may be
      associated with a range of long-term adverse effects. Here, we review the safety
      of PPIs and consider whether long-term prescribing needs to be reassessed.

PMID- 29021242
TI  - Autogenous cross-regulation of Quaking mRNA processing and translation balances
      Quaking functions in splicing and translation.
AB  - Quaking protein isoforms arise from a single Quaking gene and bind the same RNA
      motif to regulate splicing, translation, decay, and localization of a large set
      of RNAs. However, the mechanisms by which Quaking expression is controlled to
      ensure that appropriate amounts of each isoform are available for such disparate
      gene expression processes are unknown. Here we explore how levels of two
      isoforms, nuclear Quaking-5 (Qk5) and cytoplasmic Qk6, are regulated in mouse
      myoblasts. We found that Qk5 and Qk6 proteins have distinct functions in splicing
      and translation, respectively, enforced through differential subcellular
      localization. We show that Qk5 and Qk6 regulate distinct target mRNAs in the cell
      and act in distinct ways on their own and each other's transcripts to create a
      network of autoregulatory and cross-regulatory feedback controls. Morpholino
      mediated inhibition of Qk translation confirms that Qk5 controls Qk RNA levels by
      promoting accumulation and alternative splicing of Qk RNA, whereas Qk6 promotes
      its own translation while repressing Qk5. This Qk isoform cross-regulatory
      network responds to additional cell type and developmental controls to generate a
      spectrum of Qk5/Qk6 ratios, where they likely contribute to the wide range of
      functions of Quaking in development and cancer.

PMID- 29021250
TI  - Electrostatic lipid-protein interactions sequester the curli amyloid fold on the
      lipopolysaccharide membrane surface.
AB  - Curli is a functional amyloid protein in the extracellular matrix of enteric Gram
      negative bacteria. Curli is assembled at the cell surface and consists of CsgA,
      the major subunit of curli, and a membrane-associated nucleator protein, CsgB.
      Oligomeric intermediates that accumulate during the lag phase of amyloidogenesis
      are generally toxic, but the underlying mechanism by which bacterial cells
      overcome this toxicity during curli assembly at the surface remains elusive.
      Here, we elucidated the mechanism of curli amyloidogenesis and provide molecular
      insights into the strategy by which bacteria can potentially bypass the
      detrimental consequences of toxic amyloid intermediates. Using a diverse range of
      biochemical and biophysical tools involving circular dichroism, fluorescence,
      Raman spectroscopy, and atomic force microscopy imaging, we characterized the
      molecular basis of the interaction of CsgB with a membrane-mimetic anionic
      surfactant as well as with lipopolysaccharide (LPS) constituting the outer
      leaflet of Gram-negative bacteria. Aggregation studies revealed that the
      electrostatic interaction of the positively charged C-terminal region of the
      protein with a negatively charged head group of surfactant/LPS promotes a protein
      protein interaction that results in facile amyloid formation without a detectable
      lag phase. We also show that CsgB, in the presence of surfactant/LPS, accelerates
      the fibrillation rate of CsgA by circumventing the lag phase during nucleation.
      Our findings suggest that the electrostatic interactions between lipid and
      protein molecules play a pivotal role in efficiently sequestering the amyloid
      fold of curli on the membrane surface without significant accumulation of toxic
      oligomeric intermediates.

PMID- 29021251
TI  - Direct evidence for conformational dynamics in major histocompatibility complex
      class I molecules.
AB  - Major histocompatibility complex class I molecules (MHC I) help protect jawed
      vertebrates by binding and presenting immunogenic peptides to cytotoxic T
      lymphocytes. Peptides are selected from a large diversity present in the
      endoplasmic reticulum. However, only a limited number of peptides complement the
      polymorphic MHC specificity determining pockets in a way that leads to high
      affinity peptide binding and efficient antigen presentation. MHC I molecules
      possess an intrinsic ability to discriminate between peptides, which varies in
      efficiency between allotypes, but the mechanism of selection is unknown.
      Elucidation of the selection mechanism is likely to benefit future immune
      modulatory therapies. Evidence suggests peptide selection involves transient
      adoption of alternative, presumably higher energy conformations than native
      peptide-MHC complexes. However, the instability of peptide-receptive MHC
      molecules has hindered characterization of such conformational plasticity. To
      investigate the dynamic nature of MHC, we refolded MHC proteins with peptides
      that can be hydrolyzed by UV light and thus released. We compared the resultant
      peptide-receptive MHC molecules with non-hydrolyzed peptide-loaded MHC complexes
      by monitoring the exchange of hydrogen for deuterium in solution. We found
      differences in hydrogen-deuterium exchange between peptide-loaded and peptide
      receptive molecules that were negated by the addition of peptide to peptide
      receptive MHC molecules. Peptide hydrolysis caused significant increases in
      hydrogen-deuterium exchange in sub-regions of the peptide-binding domain and
      smaller increases elsewhere, including in the alpha3 domain and the non
      covalently associated beta2-microglobulin molecule, demonstrating long-range
      dynamic communication. Comparing two MHC allotypes revealed allotype-specific
      differences in hydrogen-deuterium exchange, consistent with the notion that MHC I
      plasticity underpins peptide selection.

PMID- 29021252
TI  - A chemical and biological toolbox for Type Vd secretion: Characterization of the
      phospholipase A1 autotransporter FplA from Fusobacterium nucleatum.
AB  - Fusobacterium nucleatum is an oral pathogen that is linked to multiple human
      infections and colorectal cancer. Strikingly, F. nucleatum achieves virulence in
      the absence of large, multiprotein secretion systems (Types I, II, III, IV, and
      VI), which are widely used by Gram-negative bacteria for pathogenesis. By
      contrast, F. nucleatum strains contain genomic expansions of Type V secreted
      effectors (autotransporters) that are critical for host cell adherence, invasion,
      and biofilm formation. Here, we present the first characterization of an F.
      nucleatum Type Vd phospholipase class A1 autotransporter (strain ATCC 25586, gene
      FN1704) that we hereby rename Fusobacterium phospholipase autotransporter (FplA).
      Biochemical analysis of multiple Fusobacterium strains revealed that FplA is
      expressed as a full-length 85-kDa outer membrane-embedded protein or as a
      truncated phospholipase domain that remains associated with the outer membrane.
      Whereas the role of Type Vd secretion in bacteria remains unidentified, we show
      that FplA binds with high affinity to host phosphoinositide-signaling lipids,
      revealing a potential role for this enzyme in establishing an F. nucleatum
      intracellular niche. To further analyze the role of FplA, we developed an fplA
      gene knock-out strain, which will guide future in vivo studies to determine its
      potential role in F. nucleatum pathogenesis. In summary, using recombinant FplA
      constructs, we have identified a biochemical toolbox that includes lipid
      substrates for enzymatic assays, potent inhibitors, and chemical probes to
      detect, track, and characterize the role of Type Vd secreted phospholipases in
      Gram-negative bacteria.

PMID- 29021253
TI  - Nuclear export factor 3 regulates localization of small nucleolar RNAs.
AB  - Small nucleolar RNAs (snoRNAs) guide chemical modifications of ribosomal and
      small nuclear RNAs, functions that are carried out in the nucleus. Although most
      snoRNAs reside in the nucleolus, a growing body of evidence indicates that
      snoRNAs are also present in the cytoplasm and that snoRNAs move between the
      nucleus and cytoplasm by a mechanism that is regulated by lipotoxic and oxidative
      stress. Here, in a genome-wide shRNA-based screen, we identified nuclear export
      factor 3 (NXF3) as a transporter that alters the nucleocytoplasmic distribution
      of box C/D snoRNAs from the ribosomal protein L13a (Rpl13a) locus. Using RNA
      sequencing analysis, we show that NXF3 associates not only with Rpl13a snoRNAs,
      but also with a broad range of box C/D and box H/ACA snoRNAs. Under homeostatic
      conditions, gain- or loss-of-function of NXF3, but not related family member
      NXF1, decreases or increases cytosolic Rpl13a snoRNAs, respectively. Furthermore,
      treatment with the adenylyl cyclase activator forskolin diminishes cytosolic
      localization of the Rpl13a snoRNAs through a mechanism that is dependent on NXF3
      but not NXF1. Our results provide evidence of a new role for NXF3 in regulating
      the distribution of snoRNAs between the nuclear and cytoplasmic compartments.

PMID- 29021254
TI  - Checkpoint kinase 1-induced phosphorylation of O-linked beta-N-acetylglucosamine
      transferase regulates the intermediate filament network during cytokinesis.
AB  - Checkpoint kinase 1 (Chk1) is a kinase instrumental for orchestrating DNA
      replication, DNA damage checkpoints, the spindle assembly checkpoint, and
      cytokinesis. Despite Chk1's pivotal role in multiple cellular processes, many of
      its substrates remain elusive. Here, we identified O-linked beta-N
      acetylglucosamine (O-GlcNAc)-transferase (OGT) as one of Chk1's substrates. We
      found that Chk1 interacts with and phosphorylates OGT at Ser-20, which not only
      stabilizes OGT, but also is required for cytokinesis. Phospho-specific antibodies
      of OGT-pSer-20 exhibited specific signals at the midbody of the cell, consistent
      with midbody localization of OGT as reported previously. Moreover, phospho
      deficient OGT (S20A) cells attenuated cellular O-GlcNAcylation levels and also
      reduced phosphorylation of Ser-71 in the cytoskeletal protein vimentin, a
      modification critical for severing vimentin filament during cytokinesis.
      Consequently, elongated vimentin bridges were observed in cells depleted of OGT
      via an siOGT-based approach. Lastly, expression of plasmids resistant to siOGT
      efficiently rescued the vimentin bridge phenotype, but the OGT-S20A rescue
      plasmids did not. Our results suggest a Chk1-OGT-vimentin pathway that regulates
      the intermediate filament network during cytokinesis.

PMID- 29021255
TI  - The molecular mechanism of N-acetylglucosamine side-chain attachment to the
      Lancefield group A carbohydrate in Streptococcus pyogenes.
AB  - In many Lactobacillales species (i.e. lactic acid bacteria), peptidoglycan is
      decorated by polyrhamnose polysaccharides that are critical for cell envelope
      integrity and cell shape and also represent key antigenic determinants. Despite
      the biological importance of these polysaccharides, their biosynthetic pathways
      have received limited attention. The important human pathogen, Streptococcus
      pyogenes, synthesizes a key antigenic surface polymer, the Lancefield group A
      carbohydrate (GAC). GAC is covalently attached to peptidoglycan and consists of a
      polyrhamnose polymer, with N-acetylglucosamine (GlcNAc) side chains, which is an
      essential virulence determinant. The molecular details of the mechanism of
      polyrhamnose modification with GlcNAc are currently unknown. In this report,
      using molecular genetics, analytical chemistry, and mass spectrometry analysis,
      we demonstrated that GAC biosynthesis requires two distinct undecaprenol-linked
      GlcNAc-lipid intermediates: GlcNAc-pyrophosphoryl-undecaprenol (GlcNAc-P-P-Und)
      produced by the GlcNAc-phosphate transferase GacO and GlcNAc-phosphate
      undecaprenol (GlcNAc-P-Und) produced by the glycosyltransferase GacI. Further
      investigations revealed that the GAC polyrhamnose backbone is assembled on GlcNAc
      P-P-Und. Our results also suggested that a GT-C glycosyltransferase, GacL,
      transfers GlcNAc from GlcNAc-P-Und to polyrhamnose. Moreover, GacJ, a small
      membrane-associated protein, formed a complex with GacI and significantly
      stimulated its catalytic activity. Of note, we observed that GacI homologs
      perform a similar function in Streptococcus agalactiae and Enterococcus faecalis
      In conclusion, the elucidation of GAC biosynthesis in S. pyogenes reported here
      enhances our understanding of how other Gram-positive bacteria produce essential
      components of their cell wall.

PMID- 29021256
TI  - Disruption of amyloid precursor protein ubiquitination selectively increases
      amyloid beta (Abeta) 40 levels via presenilin 2-mediated cleavage.
AB  - Amyloid plaques, a neuropathological hallmark of Alzheimer's disease, are largely
      composed of amyloid beta (Abeta) peptide, derived from cleavage of amyloid
      precursor protein (APP) by beta- and gamma-secretases. The endosome is
      increasingly recognized as an important crossroad for APP and these secretases,
      with major implications for APP processing and amyloidogenesis. Among various
      post-translational modifications affecting APP accumulation, ubiquitination of
      cytodomain lysines may represent a key signal controlling APP endosomal sorting.
      Here, we show that substitution of APP C-terminal lysines with arginine disrupts
      APP ubiquitination and that an increase in the number of substituted lysines
      tends to increase APP metabolism. An APP mutant lacking all C-terminal lysines
      underwent the most pronounced increase in processing, leading to accumulation of
      both secreted and intracellular Abeta40. Artificial APP ubiquitination with
      rapalog-mediated proximity inducers reduced Abeta40 generation. A lack of APP C
      terminal lysines caused APP redistribution from endosomal intraluminal vesicles
      (ILVs) to the endosomal limiting membrane, with a subsequent decrease in APP C
      terminal fragment (CTF) content in secreted exosomes, but had minimal effects on
      APP lysosomal degradation. Both the increases in secreted and intracellular
      Abeta40 were abolished by depletion of presenilin 2 (PSEN2), recently shown to be
      enriched on the endosomal limiting membrane compared with PSEN1. Our findings
      demonstrate that ubiquitin can act as a signal at five cytodomain-located lysines
      for endosomal sorting of APP. They further suggest that disruption of APP
      endosomal sorting reduces its sequestration in ILVs and results in PSEN2-mediated
      processing of a larger pool of APP-CTF on the endosomal membrane.

PMID- 29021258
TI  - Age, Sex, and Blood Pressure-Related Influences on Reference Values of Left
      Atrial Deformation and Mechanics From a Large-Scale Asian Population.
AB  - BACKGROUND: Left atrial (LA) function is tightly linked to several cardiovascular
      diseases and confers key prognostic information. Speckle tracking-based
      deformation as a feasible and sensitive LA mechanical assessment has proven its
      clinical significance beyond volume measures; however, the reference values
      remain largely unknown. METHODS AND RESULTS: We studied 4042 participants
      undergoing annual cardiovascular survey. Among them, 2812 healthy participants
      (65% men; mean age, 47.4+/-9.9 years) were eligible for speckle tracking
      analysis. Peak atrial longitudinal systolic strain and strain rate (SR) at
      systolic (SRs), early diastolic (SRe), and late diastolic atrial contraction
      phases (SRa) were analyzed by dedicated software (EchoPAC, GE) and compared in
      terms of age, sex, and blood pressure. Overall, women demonstrated higher peak
      atrial longitudinal systolic strain (39.34+/-7.99% versus 37.95+/-7.96%; P<0.001)
      and showed age-dependent more pronounced peak atrial longitudinal systolic strain
      functional decay than those of men (P value for interaction, <0.05), with men
      showing higher SRs and SRa, although lower SRe (all P<0.001). Both increasing age
      and higher blood pressure were independently associated with deteriorated peak
      atrial longitudinal systolic strain, SRs, and SRe, although augmented LA SRa,
      even after accounting for baseline clinical covariates in multivariable models
      that incorporated LA volume, NT-proBNP (N-terminal pro-B-type natriuretic
      peptide), or left ventricular E/e' (all P<0.001). CONCLUSIONS: Our findings
      suggest LA mechanical functional decays in association with increasing age and
      higher blood pressure, which seem to be compensated for by augmentation of atrial
      pump function. We have also provided age- and sex-stratified reference values for
      strain and SR based on a large-scale Asian population.

PMID- 29021257
TI  - Presence, Characteristics, and Prognostic Associations of Carotid Plaque Among
      People Living With HIV.
AB  - BACKGROUND: Data from broad populations have established associations between
      incidental carotid plaque and vascular events. Among people living with HIV
      (PLWHIV), the risk of vascular events is increased; however, whether incidental
      carotid plaque is increased and there is an association between incidental
      carotid plaque, plaque characteristics, and vascular events among PLWHIV is
      unclear. METHODS AND RESULTS: Data from the multi-institutional Research Patient
      Data Registry were used. Presence and characteristics (high-risk plaque,
      including spotty calcification and low attenuation) of carotid plaque by
      computerized tomography among PLWHIV without known vascular disease were
      described. Data were compared with uninfected controls similar in age, sex, and
      cardiovascular risk factors, including diabetes mellitus, hyperlipidemia, and
      cigarette smoking to cases. Primary outcome was an atherosclerotic cardiovascular
      disease event, and secondary outcome was ischemic stroke. Cohort consisted of 209
      PLWHIV (45+/-10 years, 72% male) and 168 controls. Using computerized tomography,
      PLWHIV without vascular disease had higher rates of any carotid plaque (34%
      versus 25%; P=0.04), noncalcified (18% versus 5%; P<0.001) and high-risk plaque
      (25% versus 16%; P=0.03). Over a follow-up of 3 years, 19 atherosclerotic
      cardiovascular disease events (9 strokes) occurred. Carotid plaque was
      independently associated with a 3-fold increase in atherosclerotic cardiovascular
      disease events among PLWHIV (hazard ratio, 2.91; confidence interval, 1.10-7.7,
      P=0.03) and a 4-fold increased risk of stroke (hazard ratio, 4.43; confidence
      interval, 1.17-16.70; P=0.02); high-risk plaque was associated with a 3-fold
      increased risk of atherosclerotic cardiovascular disease events and a 4-fold
      increased risk of stroke. CONCLUSIONS: There is an increase in incidental carotid
      plaque, noncalcified plaque, and high-risk plaque among PLWHIV, and the presence
      and characteristics of carotid plaque are associated with subsequent vascular
      events.

PMID- 29021259
TI  - Preload Stress Echocardiography Predicts Outcomes in Patients With Preserved
      Ejection Fraction and Low-Gradient Aortic Stenosis.
AB  - BACKGROUND: The projected aortic valve area (AVAproj) at a normal transvalvular
      flow rate using dobutamine is helpful to determine the actual severity of aortic
      stenosis (AS) and to predict risk of adverse events in low-gradient AS cases with
      unclear surgical indication. Our study aimed to identify the independent and
      incremental value of preload stress echocardiography-derived AVAproj to predict
      outcomes in patients with preserved ejection fraction and low-gradient AS.
      METHODS AND RESULTS: We prospectively performed echocardiographic studies in 79
      patients with low-gradient AS (age, 77+/-7 years; 30% men) with preload stress
      echocardiography using leg positive pressure. AVAproj was calculated using AVA
      and transvalvular flow rate at baseline and during leg positive pressure. The
      primary end point was the decision for aortic valve surgery or cardiac death.
      During a median period of 19 months, 23 patients had the decision for aortic
      valve surgery, and none died during follow-up. In a stepwise multivariable
      analysis, indexed AVAproj (AVAiproj; hazard ratio, 2.00 per 0.1 cm2/m2 decrease;
      95% confidence interval, 1.36-2.96; P<0.001) was associated with the primary end
      point. Using a receiver operating characteristic curve analysis, the best cutoff
      value of AVAiproj for predicting cardiac events was <0.72 cm2/m2. By
      incorporating AVAiproj into AVAi at baseline, continuous net reclassification
      index for cardiac events was 0.48 (P=0.04). CONCLUSIONS: In patients with low
      gradient AS, indexed AVAproj derived from preload stress echocardiography can be
      useful to predict risk of adverse events. The present article should be
      considered as a proof of concept study, and we think that larger multicenter
      studies are warranted.

PMID- 29021260
TI  - Risk Stratification of Severe Aortic Stenosis With Preserved Left Ventricular
      Ejection Fraction Using Peak Aortic Jet Velocity: An Outcome Study.
AB  - BACKGROUND: Current guidelines consider aortic valve replacement reasonable in
      asymptomatic patients with very severe aortic stenosis (AS); however, the
      definition of very severe AS based on peak aortic jet velocity (Vmax) remains
      unclear with a 5-m/s cutoff in US guidelines and 5.5 m/s in European guidelines.
      Because ~20% of patients with severe AS and preserved left ventricular ejection
      fraction have Vmax in this range, we aimed to assess the relationship between
      Vmax and mortality and determine the best threshold to define very severe AS.
      METHODS AND RESULTS: A total of 1140 patients with severe AS (aortic valve area
      <=1 cm2, Vmax >=4 m/s) and preserved left ventricular ejection fraction were
      included. The population was divided into 4 groups according to Vmax (4-4.49, 4.5
      4.99, 5-5.49, and >=5.5 m/s). After adjustment for covariates (including
      surgery), there was no difference in all-cause mortality between Vmax 4 to 4.49
      m/s and Vmax 4.5 to 4.99 m/s (P=0.64). Both Vmax 5 to 5.49 m/s and Vmax >=5.5 m/s
      exhibited significant excess mortality compared with Vmax 4 to 4.49 m/s (adjusted
      hazard ratio=1.34 [1.18-1.52]; P<0.001, and 1.28 [1.16-1.41]; P<0.001,
      respectively). Mortality risk was similar for Vmax 5 to 5.49 m/s and Vmax >=5.5
      m/s (P=0.93). Compared with Vmax <5 m/s, patients with Vmax >=5 m/s had greater
      mortality risk (adjusted hazard ratio=1.86 [1.55-2.54]; P<0.001), even in the
      subgroup of asymptomatic even in the subgroup of asymptomatic patients (adjusted
      hazard ratio=2.08 [1.25-3.46]; P=0.005). CONCLUSIONS: Our results demonstrate the
      strong relationship between Vmax and mortality in patients with severe AS and
      preserved left ventricular ejection fraction irrespective of symptoms. Vmax >=5
      m/s at the time of AS diagnosis identifies patients with very severe AS at high
      risk of death.

PMID- 29021261
TI  - Letter by Chung and Kim Regarding Article, "Head-to-Head Comparison of
      Inflammation and Neovascularization in Human Carotid Plaques: Implications for
      the Imaging of Vulnerable Plaques".

PMID- 29021262
TI  - Response by Demeure et al to Letter Regarding Article, "Head-to-Head Comparison
      of Inflammation and Neovascularization in Human Carotid Plaques: Implications for
      the Imaging of Vulnerable Plaques".

PMID- 29021263
TI  - Left Atrial Strain: A Must or a Plus for Routine Clinical Practice?

PMID- 29021264
TI  - Preload Stress Echocardiography: A New Tool to Confirm Severity of Low-Gradient
      Aortic Stenosis.

PMID- 29021265
TI  - Assessment of the Patient With Severe Aortic Stenosis: Getting Closer to the
      Truth.

PMID- 29021266
TI  - Imaging to End Points: Cardiovascular Disease Risk Assessment in HIV.

PMID- 29021269
TI  - "Road Map" to Improving Enrollment in Cardiac Rehabilitation: Identifying
      Barriers and Evaluating Alternatives.

PMID- 29021267
TI  - Association of Neighborhood Socioeconomic Context With Participation in Cardiac
      Rehabilitation.
AB  - BACKGROUND: Cardiac rehabilitation (CR) is underutilized in the United States,
      with fewer than 20% of eligible patients participating in CR programs. Individual
      socioeconomic status is associated with CR utilization, but data regarding
      neighborhood characteristics and CR are sparse. We investigated the association
      of neighborhood socioeconomic context with CR participation in the SCCS (Southern
      Community Cohort Study). METHODS AND RESULTS: The SCCS is a prospective cohort
      study of 84 569 adults in the southeastern United States from 2002 to 2009, 52
      117 of whom have Medicare or Medicaid claims. Using these data, we identified
      participants with hospitalizations for myocardial infarction, percutaneous
      coronary intervention, or coronary artery bypass surgery and ascertained their CR
      utilization. Neighborhood socioeconomic context was assessed using a neighborhood
      deprivation index derived from 11 census-tract level variables. We analyzed the
      association of CR utilization with neighborhood deprivation after adjusting for
      individual socioeconomic status. A total of 4096 SCCS participants (55% female,
      57% black) with claims data were eligible for CR. CR utilization was low, with
      340 subjects (8%) participating in CR programs. Study participants residing in
      the most deprived communities (highest quintile of neighborhood deprivation) were
      less than half as likely to initiate CR (odds ratio 0.42, 95% confidence
      interval, 0.27-0.66, P<0.001) as those in the lowest quintile. CR participation
      was inversely associated with all-cause mortality (hazard ratio 0.77, 95%
      confidence interval, 0.60-0.996, P<0.05). CONCLUSIONS: Lower neighborhood
      socioeconomic context was associated with decreased CR participation independent
      of individual socioeconomic status. These data invite research on interventions
      to increase CR access in deprived communities.

PMID- 29021268
TI  - Tai Chi Is a Promising Exercise Option for Patients With Coronary Heart Disease
      Declining Cardiac Rehabilitation.
AB  - BACKGROUND: More than 60% of patients decline participation in cardiac
      rehabilitation after a myocardial infarction. Options to improve physical
      activity (PA) and other risk factors in these high-risk individuals are limited.
      We conducted a phase 2 randomized controlled trial to determine feasibility,
      safety, acceptability, and estimates of effect of tai chi on PA, fitness, weight,
      and quality of life. METHODS AND RESULTS: Patients with coronary heart disease
      declining cardiac rehabilitation enrollment were randomized to a "LITE" (2
      sessions/week for 12 weeks) or to a "PLUS" (3 sessions/week for 12 weeks, then
      maintenance classes for 12 additional weeks) condition. PA (accelerometry),
      weight, and quality of life (Health Survey Short Form) were measured at baseline
      and 3, 6, and 9 months after baseline; aerobic fitness (stress test) was measured
      at 3 months. Twenty-nine participants (13 PLUS and 16 LITE) were enrolled.
      Retention at 9 months was 90% (LITE) and 88% (PLUS). No serious tai chi-related
      adverse events occurred. Significant mean between group differences in favor of
      the PLUS group were observed at 3 and 6 months for moderate-to-vigorous PA
      (100.33 min/week [95% confidence interval, 15.70-184.95 min/week] and 111.62
      min/week; [95% confidence interval, 26.17-197.07 min/week], respectively, with a
      trend toward significance at 9 months), percentage change in weight, and quality
      of life. No changes in aerobic fitness were observed within and between groups.
      CONCLUSIONS: In this community sample of patients with coronary heart disease
      declining enrollment in cardiac rehabilitation, a 6-month tai chi program was
      safe and improved PA, weight, and quality of life compared with a 3-month
      intervention. Tai chi could be an effective option to improve PA in this high
      risk population. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT02165254.

PMID- 29021270
TI  - Benefits of Cardiac Rehabilitation on Cardiovascular Outcomes in Patients With
      Diabetes Mellitus After Percutaneous Coronary Intervention.
AB  - BACKGROUND: Participation in cardiac rehabilitation (CR) is an essential
      component of care for patients with coronary artery disease. However, little is
      known about its benefit on cardiovascular outcomes in patients with diabetes
      mellitus (DM) who have undergone percutaneous coronary intervention. The aim of
      our study was to evaluate the impact of CR in this high-risk group of patients.
      METHODS AND RESULTS: We performed a retrospective analysis of all patients with
      DM who underwent percutaneous coronary intervention in Olmsted County (Minnesota)
      between 1994 and 2010, assessing the impact of CR participation on clinical
      outcomes. CR participation was significantly lower in patients with DM (38%,
      263/700) compared with those who did not have DM (45%, 1071/2379; P=0.004). Using
      propensity score adjustment, we found that in patients with DM, CR participation
      was associated with significantly reduced all-cause mortality (hazard ratio,
      0.56; 95% confidence interval, 0.39-0.80; P=0.002) and composite end point of
      mortality, myocardial infarction, or revascularization (hazard ratio, 0.77; 95%
      confidence interval, 0.60-0.98; P=0.037), during a median follow-up of 8.1 years.
      In patients without DM, CR participation was associated with a significant
      reduction in all-cause mortality (hazard ratio, 0.67; 95% confidence interval,
      0.55-0.82; P<0.001) and cardiac mortality (hazard ratio, 0.67; 95% confidence
      interval, 0.47-0.95; P=0.024). CONCLUSIONS: CR participation after percutaneous
      coronary intervention is associated with lower all-cause mortality rates in
      patients with DM, to a similar degree as for those without DM. However, CR
      participation was lower in patients with DM, suggesting the need to identify and
      correct the barriers to CR participation for this higher-risk group of patients.

PMID- 29021271
TI  - Impact of Hemodialysis on Procedural Outcomes of Percutaneous Coronary
      Intervention for Chronic Total Occlusion: Insights From the Japanese Multicenter
      Registry.
AB  - BACKGROUND: Among patients treated with percutaneous coronary intervention for
      chronic total occlusion (CTO-PCI), patients on long-term hemodialysis are at
      significantly high risk for cardiovascular mortality and morbidity. However,
      clinical or angiographic predictors that might aid in better patient selection
      remain unclear. We aimed to assess the acute impact of hemodialysis in patients
      who underwent CTO-PCI. METHODS AND RESULTS: The Retrograde Summit registry is a
      multicenter, prospective registry of patients undergoing CTO-PCI at 65 Japanese
      centers. Patient characteristics and procedural outcomes of 4749 patients were
      analyzed, according to the presence (n=313) or absence (n=4436) of baseline
      hemodialysis. A prediction model for technical failure among hemodialysis
      patients was also developed. The technical success rate of CTO-PCI was
      significantly lower in hemodialysis than in nonhemodialysis patients (78.0%
      versus 89.1%, P<0.001). The rates of in-hospital major adverse cardiac and
      cerebrovascular events were similar between the 2 groups (1.6% versus 0.9%,
      P=0.24). Irrespective of clinical/angiographic characteristics or previously
      developed scoring systems, hemodialysis independently predicted technical failure
      for CTO-PCI. Among hemodialysis patients, predictors of technical failure were
      blunt stump (odds ratio 2.45, 95% confidence interval, 1.15-5.21, P=0.021),
      severe lesion calcification (odds ratio 2.50, 95% confidence interval, 1.19-5.24,
      P=0.015), and absence of diabetes mellitus (odds ratio 3.15, 95% confidence
      interval, 1.49-6.64, P=0.003). In hemodialysis patients without these predictors,
      the technical success rate was 96.2%. CONCLUSIONS: Hemodialysis is significantly
      associated with technical failure. Contemporary CTO-PCI seems feasible and safe
      in selected hemodialysis patients.

PMID- 29021273
TI  - Improvement in Care and Outcomes for Emergency Medical Service-Transported
      Patients With ST-Elevation Myocardial Infarction (STEMI) With and Without
      Prehospital Cardiac Arrest: A Mission: Lifeline STEMI Accelerator Study.
AB  - BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) with out-of
      hospital cardiac arrest (OHCA) may benefit from direct transport to a
      percutaneous cardiac intervention (PCI) hospital but have previously been less
      likely to bypass local non-PCI hospitals to go to a PCI center. METHODS AND
      RESULTS: We reported time trends in emergency medical service transport and care
      of patients with STEMI with and without OHCA included from 171 PCI-capable
      hospitals in 16 US regions with participation in the Mission: Lifeline STEMI
      Accelerator program between July 1, 2012, and March 31, 2014. Time trends by
      quarter were assessed using logistic regression with generalized estimating
      equations to account for hospital clustering. Of 13 189 emergency medical service
      transported patients, 88.7% (N=11 703; 10.5% OHCA) were taken directly to PCI
      hospitals. Among 1486 transfer-in patients, 21.7% had OHCA. Direct transport to a
      PCI center for OHCA increased from 74.7% (July 1, 2012) to 83.6% (March 31, 2014)
      (odds ratio per quarter, 1.07; 95% confidence interval, 1.02-1.14), versus 89.0%
      to 91.0% for patients without OHCA (odds ratio, 1.03; 95% confidence interval,
      0.99-1.07; interaction P=0.23). The proportion with prehospital ECGs increased
      for patients taken directly to PCI centers (53.9%-61.9% for those with OHCA
      versus 73.9%-81.9% for those without OHCA; interaction P=0.12). Of 997 patients
      with OHCA taken directly to PCI hospitals and treated with primary PCI, first
      medical contact-to-device times within the guideline-recommended goal of <=90
      minutes were met for 34.5% on July 1, 2012, versus 41.8% on March 31, 2014 (51.6%
      and 56.1%, respectively, for 9352 counterparts without OHCA; interaction P=0.72).
      CONCLUSIONS: Direct transport to PCI hospitals increased for patients with STEMI
      with and without OHCA during the 2012 to 2014 Mission: Lifeline STEMI Accelerator
      program. Proportions with prehospital ECGs and timely reperfusion increased for
      patients taken directly to PCI hospitals.

PMID- 29021272
TI  - Combined Salt and Caloric Restrictions: Potential Adverse Outcomes.
AB  - BACKGROUND: We hypothesized that caloric restriction (CR) and salt restriction
      (ResS) would have similar effects on reducing cardiovascular risk markers and
      that combining CR and ResS would be synergistic in modulating these markers.
      METHODS AND RESULTS: To test our hypothesis, rats were randomized into 2 groups:
      ad libitum liberal salt diet (ad libitum/high-sodium, 1.6% sodium) or ResS diet
      (ad libitum/ResS, 0.03% sodium). CR was initiated in half of the rats in each
      group by reducing caloric intake to 60% while maintaining sodium intake constant
      (CR/high-sodium, 2.7% sodium or CR/ResS, 0.05% sodium) for 4 weeks. CR in rats on
      a high-sodium diet improved metabolic parameters, renal transforming growth
      factor-beta and collagen-1alpha1 and increased plasma adiponectin and renal
      visfatin and NAD+ protein levels. Although CR produced some beneficial
      cardiovascular effects (increased sodium excretion and reduced blood pressure),
      it also was associated with potentially adverse cardiovascular effects. Adrenal
      zona glomerulosa cell responsiveness and aldosterone levels and activation were
      inappropriately increased for the volume state of the rodent. Like CR on HS, CR
      on a ResS diet also produced relative increased zona glomerulosa responsiveness
      and an increased blood pressure with no improvement in metabolic parameters.
      CONCLUSIONS: These results suggest that combining CR and ResS may decrease the
      beneficial effects of each alone. Furthermore, CR, regardless of dietary salt
      intake, inappropriately activates aldosterone production. Thus, caution should be
      used in combining ResS and CR because the combination may lead to increased
      cardiovascular risk.

PMID- 29021274
TI  - Prevalence and Outcomes of Left-Sided Valvular Heart Disease Associated With
      Chronic Kidney Disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is an adverse prognostic marker for
      valve intervention patients; however, the prevalence and related outcomes of
      valvular heart disease in CKD patients is unknown. METHODS AND RESULTS: Included
      patients underwent echocardiography (1999-2013), had serum creatinine values
      within 6 months before index echocardiogram, and had no history of valve surgery.
      CKD was defined as diagnosis based on the International Classification of
      Diseases, Ninth Revision or an estimated glomerular filtration rate <60 mL/min
      per 1.73 m2. Qualitative assessment determined left heart stenotic and
      regurgitant valve lesions. Cox models assessed CKD and aortic stenosis (AS)
      interaction for subsequent mortality; analyses were repeated for mitral
      regurgitation (MR). Among 78 059 patients, 23 727 (30%) had CKD; of these, 1326
      were on hemodialysis. CKD patients were older; female; had a higher prevalence of
      hypertension, hyperlipidemia, diabetes, history of coronary artery bypass
      grafting/percutaneous coronary intervention, atrial fibrillation, and heart
      failure >=mild AS; and >=mild MR (all P<0.001). Five-year survival estimates of
      mild, moderate, and severe AS for CKD patients were 40%, 34%, and 42%,
      respectively, and 69%, 54%, and 67% for non-CKD patients. Five-year survival
      estimates of mild, moderate, and severe MR for CKD patients were 51%, 38%, and
      37%, respectively, and 75%, 66%, and 65% for non-CKD patients. Significant
      interaction occurred among CKD, AS/MR severity, and mortality in adjusted
      analyses; the CKD hazard ratio increased from 1.8 (non-AS patients) to 2.0
      (severe AS) and from 1.7 (non-MR patients) to 2.6 (severe MR). CONCLUSIONS:
      Prevalence of at least mild AS and MR is substantially higher and is associated
      with significantly lower survival among patients with versus without CKD. There
      is significant interaction among CKD, AS/MR severity, and mortality, with
      increasingly worse outcomes for CKD patients with increasing AS/MR severity.

PMID- 29021275
TI  - Impact of Coronary Artery Disease on 30-Day and 1-Year Mortality in Patients
      Undergoing Transcatheter Aortic Valve Replacement: A Meta-Analysis.
AB  - BACKGROUND: The impact of coronary artery disease (CAD) on outcomes after
      transcatheter aortic valve replacement (TAVR) is understudied. Literature on the
      prognostic role of CAD in the survival of patients undergoing TAVR shows
      conflicting results. This meta-analysis aims to investigate how CAD impacts
      patient survival following TAVR. METHODS AND RESULTS: We completed a
      comprehensive literature search of Embase, MEDLINE, and the Cochrane Library, and
      included studies reporting outcome of TAVR based on CAD status of patients for
      the analysis. From the initial 1631 citations, 15 studies reporting on 8013
      patients were analyzed using a random-effects model. Of the 8013 patients
      undergoing TAVR, with a median age of 81.3 years (79-85.1 years), 46.6% (40-55.7)
      were men and 3899 (48.7%) had CAD (ranging from 30.8% to 78.2% in various
      studies). Overall, 3121 SAPIEN/SAPIEN XT/SAPIEN 3 (39.6%) and 4763 CoreValve
      (60.4%) prostheses were implanted, with transfemoral access being the most
      frequently used approach for the implantation (76.1%). Our analysis showed no
      significant difference between patients with and without CAD for all-cause
      mortality at 30 days post TAVR, with a cumulative odds ratio of 1.07 (95%
      confidence interval, 0.82-1.40; P=0.62). However, there was a significant
      increase in all-cause mortality at 1 year in the CAD group compared with patients
      without CAD, with a cumulative odds ratio of 1.21 (95% confidence interval, 1.07
      1.36; P=0.002). CONCLUSIONS: Even though coexisting CAD does not impact 30-day
      mortality, it does have an impact on 1-year mortality in patients undergoing
      TAVR. Our results highlight a need to revisit the revascularization strategies
      for concomitant CAD in patients with TAVR.

PMID- 29021276
TI  - Economic Impact of Subsequent Depression in Patients With a New Diagnosis of
      Stable Angina: A Population-Based Study.
AB  - BACKGROUND: Depression is strongly linked to increased morbidity and mortality in
      patients with chronic stable angina; however, its associated healthcare costs
      have been less well studied. Our objective was to identify the characteristics of
      chronic stable patients found to have depression and to determine the impact of
      an occurrence of depression on healthcare costs within 1 year of a diagnosis of
      stable angina. METHODS AND RESULTS: In this population-based study conducted in
      Ontario, Canada, we identified patients diagnosed with stable angina based on
      angiogram between October 1, 2008, and September 30, 2013. Depression was
      ascertained by physician billing codes and hospital admission diagnostic codes
      contained within administrative databases. The primary outcome was cumulative
      mean 1-year healthcare costs following index angiogram. Generalized linear models
      were developed with a logarithmic link and gamma distribution to determine
      predictors of cost. Our cohort included 22 917 patients with chronic stable
      angina. Patients with depression had significantly higher mean 1-year healthcare
      costs ($32 072+/-$41 963) than patients without depression ($23 021+/-$25 741).
      After adjustment for baseline comorbidities, depression was found to be a
      significant independent predictor of cost, with a cost ratio of 1.33 (95%
      confidence interval, 1.29-1.37). Higher costs in depressed patients were seen in
      all healthcare sectors, including acute and ambulatory care. CONCLUSIONS:
      Depression is an important driver of healthcare costs in patients following a
      diagnosis of chronic stable angina. Further research is needed to understand
      whether improvements in the approach to diagnosis and treatment of depression
      will translate to reduced expenditures in this population.

PMID- 29021277
TI  - Cardiometabolic Risk Variables in Preadolescent Children: A Factor Analysis.
AB  - BACKGROUND: Atherosclerosis begins during preadolescence and is occurring at an
      accelerated rate. This acceleration has been linked to poor lifestyle behaviors
      and subsequent cardiometabolic complications. Although the clustering of
      cardiometabolic risk factors has been recognized for over 2 decades, previous
      studies in children have predominantly examined the relationships between
      atherosclerosis and individual cardiometabolic risk factors or have grouped
      together preadolescent and adolescent children. Further, no known studies have
      included glycated hemoglobin or central hemodynamic measures such as central
      systolic blood pressure and augmentation index. METHODS AND RESULTS: Principal
      component analysis was performed on a cross-sectional sample of 392 children
      (aged 9.5 years, 50% girls) from 3 representative sample sites across New
      Zealand. Four factors explained 60% of the variance in the measured variables. In
      order of variance explained, the factors were: blood pressure (central systolic
      blood pressure and peripheral systolic and diastolic blood pressure), adiposity
      (waist circumference, body mass index, and glycated hemoglobin), lipids (total
      cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein
      cholesterol), and vascular (augmentation index, heart rate, and fasting blood
      glucose). CONCLUSIONS: In accordance with previous findings in adults and
      adolescents, one common factor is unlikely to define cardiometabolic health in
      preadolescent children. Each of the factors, except vascular, which was
      predominantly explained by augmentation index, are in agreement with previous
      findings in adolescents. An additional novel finding was that glycated hemoglobin
      and fasting blood glucose loaded onto different factors, supporting previous work
      suggesting that fasting blood glucose indicates short-term glycemic control,
      whereas glycated hemoglobin reflects chronic glycemic control. CLINICAL TRIAL
      REGISTRATION: URL: www.anzctr.org.au/. ID: ACTRN12614000433606.

PMID- 29021279
TI  - Long-Term Fragility of Y Chromosomes Is Dominated by Short-Term Resolution of
      Sexual Antagonism.
AB  - The evolution of heteromorphic sex chromosomes has fascinated biologists,
      inspiring theoretical models, experimental studies, and studies of genome
      structure. This work has produced a clear model, in which heteromorphic sex
      chromosomes result from repeated fixations of inversions (or other recombination
      suppression mechanisms) that tether sexually antagonistic alleles to sex
      determining regions, followed by the degeneration of these regions induced by the
      lack of sex chromosome recombination in the heterogametic sex. However, current
      models do not predict if inversions are expected to preferentially accumulate on
      one sex-chromosome or another, and do not address if inversions can accumulate
      even when they cause difficulties in pairing between heteromorphic chromosomes in
      the heterogametic sex increasing aneuploidy or meiotic arrest. To address these
      questions, we developed a population genetic model in which the sex chromosome
      aneuploidy rate is elevated when males carry an inversion on either the X or Y
      chromosome. We show that inversions fix more easily when male-beneficial alleles
      are dominant, and that inversions on the Y chromosome fix with lower selection
      coefficients than comparable X chromosome inversions. We further show that sex
      chromosome inversions can often invade and fix despite causing a substantial
      increase in the risk of aneuploidy. As sexual antagonism can lead to the fixation
      of inversions that increase sex chromosomes aneuploidy (which underlies genetic
      diseases including Klinefelter and Turner syndrome in humans) selection could
      subsequently favor diverse mechanisms to reduce aneuploidy-including alternative
      meiotic mechanisms, translocations to, and fusions with, the sex chromosomes, and
      sex chromosome turnover.

PMID- 29021278
TI  - Dual Roles of Glutathione in Ecdysone Biosynthesis and Antioxidant Function
      During Larval Development in Drosophila.
AB  - Ecdysteroids, including the biologically active hormone 20-hydroxyecdysone (20E),
      play essential roles in controlling many developmental and physiological events
      in insects. Ecdysteroid biosynthesis is achieved by a series of specialized
      enzymes encoded by the Halloween genes. Recently, a new class of Halloween gene,
      noppera-bo (nobo), encoding a glutathione S-transferase (GST) in dipteran and
      lepidopteran species, has been identified and characterized. GSTs are well known
      to conjugate substrates with the reduced form of glutathione (GSH), a bioactive
      tripeptide composed of glutamate, cysteine, and glycine. We hypothesized that GSH
      itself is required for ecdysteroid biosynthesis. However, the role of GSH in
      steroid hormone biosynthesis has not been examined in any organisms. Here, we
      report phenotypic analysis of a complete loss-of-function mutant in the gamma
      glutamylcysteine synthetase catalytic subunit (Gclc) gene in the fruit fly
      Drosophila melanogasterGclc encodes the evolutionarily conserved catalytic
      component of the enzyme that conjugates glutamate and cysteine in the GSH
      biosynthesis pathway. Complete Gclc loss-of-function leads to drastic GSH
      deficiency in the larval body fluid. Gclc mutant animals show a larval-arrest
      phenotype. Ecdysteroid titer in Gclc mutant larvae decreases, and the larval
      arrest phenotype is rescued by oral administration of 20E or cholesterol.
      Moreover, Gclc mutant animals exhibit abnormal lipid deposition in the
      prothoracic gland, a steroidogenic organ during larval development. All of these
      phenotypes are reminiscent to nobo loss-of-function animals. On the other hand,
      Gclc mutant larvae also exhibit a significant reduction in antioxidant capacity.
      Consistent with this phenotype, Gclc mutant larvae are more sensitive to
      oxidative stress response as compared to wild-type. Nevertheless, the ecdysteroid
      biosynthesis defect in Gclc mutant animals is not associated with loss of
      antioxidant function. Our data raise the unexpected hypothesis that a primary
      role of GSH in early D. melanogaster larval development is ecdysteroid
      biosynthesis, independent from the antioxidant role of GSH.

PMID- 29021283
TI  - Variations in energy intake: it is more complicated than we think.

PMID- 29021280
TI  - Primary Cilium Formation and Ciliary Protein Trafficking Is Regulated by the
      Atypical MAP Kinase MAPK15 in Caenorhabditis elegans and Human Cells.
AB  - Motile and immotile (or primary) cilia are microtubule-based structures that
      mediate multiple cellular functions, including the transduction of environmental
      cues, developmental signaling, cellular motility, and modulation of fluid flow.
      Although their core architectures are similar, motile and primary cilia exhibit
      marked structural differences that underlie distinct functional properties.
      However, the extent to which ciliogenesis mechanisms are shared between these
      different cilia types is not fully described. Here, we report that the atypical
      MAP kinase MAPK15 (ERK7/8), implicated in the formation of vertebrate motile
      cilia, also regulates the formation of primary cilia in Caenorhabditis elegans
      sensory neurons and human cells. We find that MAPK15 localizes to a basal body
      subdomain with the ciliopathy protein BBS7 and to cell-cell junctions. MAPK15
      also regulates the localization of ciliary proteins involved in cilium structure,
      transport, and signaling. Our results describe a primary cilia-related role for
      this poorly studied member of the MAPK family in vivo, and indicate a broad
      requirement for MAPK15 in the formation of multiple ciliary classes across
      species.

PMID- 29021284
TI  - When to eat!

PMID- 29021281
TI  - Survival of BRCA2-Deficient Cells Is Promoted by GIPC3, a Novel Genetic
      Interactor of BRCA2.
AB  - BRCA2 loss-of-heterozygosity (LOH) is frequently observed in BRCA2-mutated
      tumors, but its biallelic loss causes embryonic lethality in mice and inhibits
      proliferation of normal somatic cells. Therefore, it remains unclear how loss of
      BRCA2 contributes to tumorigenesis. One possibility is that mutation in potential
      genetic interactors of BRCA2, such as TRP53, is required for cell
      survival/proliferation in the absence of BRCA2. In this study, using an
      insertional mutagenesis screen in mouse embryonic stem cells (mESC), we have
      identified GIPC3 (GAIP-interacting protein C-terminus 3) as a BRCA2 genetic
      interactor that contributes to survival of Brca2-null mESC. GIPC3 does not
      compensate for BRCA2 loss in the repair of double-strand breaks. Mass
      spectrometric analysis resulted in the identification of G-protein signaling
      transducers, APPL1 and APPL2, as potential GIPC3-binding proteins. A mutant GIPC3
      (His155Ala) that does not bind to APPL1/2 failed to rescue the lethality of Brca2
      null mESC, suggesting that the cell viability by GIPC3 is mediated via APPL1/2.
      Finally, the physiological significance of GIPC3 as a genetic interactor of BRCA2
      is supported by the observation that Brca2-null embryos with Gipc3 overexpression
      are developmentally more advanced than their control littermates. Taken together,
      we have uncovered a novel role for GIPC3 as a BRCA2 genetic interactor.

PMID- 29021282
TI  - Methionine metabolism is essential for SIRT1-regulated mouse embryonic stem cell
      maintenance and embryonic development.
AB  - Methionine metabolism is critical for epigenetic maintenance, redox homeostasis,
      and animal development. However, the regulation of methionine metabolism remains
      unclear. Here, we provide evidence that SIRT1, the most conserved mammalian NAD+
      dependent protein deacetylase, is critically involved in modulating methionine
      metabolism, thereby impacting maintenance of mouse embryonic stem cells (mESCs)
      and subsequent embryogenesis. We demonstrate that SIRT1-deficient mESCs are
      hypersensitive to methionine restriction/depletion-induced differentiation and
      apoptosis, primarily due to a reduced conversion of methionine to S
      adenosylmethionine. This reduction markedly decreases methylation levels of
      histones, resulting in dramatic alterations in gene expression profiles.
      Mechanistically, we discover that the enzyme converting methionine to S
      adenosylmethionine in mESCs, methionine adenosyltransferase 2a (MAT2a), is under
      control of Myc and SIRT1. Consistently, SIRT1 KO embryos display reduced Mat2a
      expression and histone methylation and are sensitive to maternal methionine
      restriction-induced lethality, whereas maternal methionine supplementation
      increases the survival of SIRT1 KO newborn mice. Our findings uncover a novel
      regulatory mechanism for methionine metabolism and highlight the importance of
      methionine metabolism in SIRT1-mediated mESC maintenance and embryonic
      development.

PMID- 29021286
TI  - Pomegranate juice, but not an extract, confers a lower glycemic response on a
      high-glycemic index food: randomized, crossover, controlled trials in healthy
      subjects.
AB  - Background: Low-glycemic index diets have demonstrated health benefits associated
      with a reduced risk of developing type 2 diabetes.Objectives: We tested whether
      pomegranate polyphenols could lower the glycemic response of a high-glycemic
      index food when consumed together and the mechanism by which this might
      occur.Design: We compared the acute effect of a pomegranate juice and a
      polyphenol-rich extract from pomegranate (supplement) on the bread-derived
      postprandial blood glucose concentration in 2 randomized, crossover, controlled
      studies (double-blinded for the supplements), each on 16 healthy volunteers. An
      additional randomized, crossover, controlled study on 16 volunteers consuming
      constituent fruit acids in a pH-balanced solution (same pH as pomegranate) and
      bread was conducted to determine any contributions to postprandial responses
      caused by acidic beverages.Results: As primary outcome, the incremental area
      under the curve for bread-derived blood glucose (-33.1% +/- 18.1%, P = 0.000005)
      and peak blood glucose (25.4% +/- 19.3%, P = 0.0004) were attenuated by
      pomegranate juice, compared with a control solution containing the equivalent
      amount of sugars. In contrast, the pomegranate supplement, or a solution
      containing the malic and citric acid components of the juice, was ineffective.
      The pomegranate polyphenol punicalagin was a very effective inhibitor of human
      alpha-amylase in vitro, comparable to the drug acarbose. Neither the pomegranate
      extract nor the individual component polyphenols inhibited 14C-D-glucose
      transport across differentiated Caco-2/TC7 cell monolayers, but they inhibited
      uptake of 14C-glucose into Xenopus oocytes expressing the human glucose
      transporter type 2. Further, some of the predicted pomegranate gut microbiota
      metabolites modulated 14C-D-glucose and 14C-deoxy-D-glucose uptake into hepatic
      HepG2 cells.Conclusions: These data indicate that pomegranate polyphenols, when
      present in a beverage but not in a supplement, can reduce the postprandial
      glycemic response of bread, whereas microbial metabolites from pomegranate
      polyphenols exhibit the potential to further modulate sugar metabolism much later
      in the postprandial period. This trial was registered at clinicaltrials.gov as
      NCT02486978, NCT02624609, and NCT03242876.

PMID- 29021285
TI  - Placental vitamin D metabolism and its associations with circulating vitamin D
      metabolites in pregnant women.
AB  - Background: Little is known about placental vitamin D metabolism and its impact
      on maternal circulating vitamin D concentrations in humans.Objective: This study
      sought to advance the current understanding of placental vitamin D metabolism and
      its role in modulating maternal circulating vitamin D metabolites during
      pregnancy.Design: Nested within a feeding study, 24 healthy pregnant women (26-29
      wk of gestation) consumed a single amount of vitamin D (511 IU/d from diet and a
      cholecalciferol supplement) for 10 wk. Concentrations of placental and blood
      vitamin D metabolites and placental messenger RNA (mRNA) abundance of vitamin D
      metabolic pathway components were quantified. In addition, cultured human
      trophoblasts were incubated with 13C-cholecalciferol to examine the intracellular
      generation and secretion of vitamin D metabolites along with the regulation of
      target genes.Results: In placental tissue, 25-hydroxyvitamin D3 [25(OH)D3] was
      strongly correlated (r = 0.83, P < 0.001) with 24,25-dihydroxyvitamin D3
      Moreover, these placental metabolites were strongly correlated (r <= 0.85, P <=
      0.04) with their respective metabolites in maternal circulation. Positive
      associations (P <= 0.045) were also observed between placental mRNA abundance of
      vitamin D metabolic components and circulating vitamin D metabolites [i.e., LDL
      related protein 2 (LRP2, also known as megalin) with 25(OH)D3 and the C3 epimer
      of 25(OH)D3 [3-epi-25(OH)D3]; cubilin (CUBN) with 25(OH)D3; 25-hydroxylase
      (CYP2R1) with 3-epi-25(OH)D3; 24-hydroxylase (CYP24A1) with 25(OH)D3, 3-epi
      25(OH)D3, and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]; and 1alpha-hydroxylase
      [(CYP27B1) with 3-epi-25(OH)D3 and 1,25(OH)2D3]. Notably, in vitro experiments
      with trophoblasts showed increased production and secretion of 25(OH)D3 and
      higher CYP24A1 gene transcript abundance in response to cholecalciferol
      treatment.Conclusions: The numerous associations of many of the placental
      biomarkers of vitamin D metabolism with circulating vitamin D metabolites among
      pregnant women [including a CYP27B1-associated increase in 1,25(OH)2D3] and the
      evidence of trophoblast production and secretion of vitamin D metabolites,
      especially 25(OH)D3, suggest that the placenta may play an active role in
      modulating the vitamin D metabolite profile in maternal circulation in human
      pregnancy. This trial was registered at clinicaltrials.gov as NCT03051867.

PMID- 29021287
TI  - Surrogate disease markers as substitutes for chronic disease outcomes in studies
      of diet and chronic disease relations.
AB  - Surrogate biomarkers for clinical outcomes afford scientific and economic
      efficiencies when investigating nutritional interventions in chronic diseases.
      However, valid scientific results are dependent on the qualification of these
      disease markers that are intended to be substitutes for a clinical outcome and to
      accurately predict benefit or harm. In this article, we examine the challenges of
      evaluating surrogate markers and describe the framework proposed in a 2010
      Institute of Medicine report. The components of this framework are presented in
      the context of nutritional interventions for chronic diseases. We present case
      studies of 2 well-accepted surrogate markers [blood pressure within sodium intake
      and cardiovascular disease (CVD) context and low density lipoprotein-cholesterol
      concentrations within a saturated fat and CVD context]. We also describe
      additional cases in which the evidence is insufficient to validate their
      surrogate status. Guidance is offered for future research that evaluates or uses
      surrogate markers.

PMID- 29021289
TI  - Quantifying the regulatory effect size of cis-acting genetic variation using
      allelic fold change.
AB  - Mapping cis-acting expression quantitative trait loci (cis-eQTL) has become a
      popular approach for characterizing proximal genetic regulatory variants. In this
      paper, we describe and characterize log allelic fold change (aFC), the magnitude
      of expression change associated with a given genetic variant, as a biologically
      interpretable unit for quantifying the effect size of cis-eQTLs and a
      mathematically convenient approach for systematic modeling of cis-regulation.
      This measure is mathematically independent from expression level and allele
      frequency, additive, applicable to multiallelic variants, and generalizable to
      multiple independent variants. We provide efficient tools and guidelines for
      estimating aFC from both eQTL and allelic expression data sets and apply it to
      Genotype Tissue Expression (GTEx) data. We show that aFC estimates independently
      derived from eQTL and allelic expression data are highly consistent, and identify
      technical and biological correlates of eQTL effect size. We generalize aFC to
      analyze genes with two eQTLs in GTEx and show that in nearly all cases the two
      eQTLs act independently in regulating gene expression. In summary, aFC is a solid
      measure of cis-regulatory effect size that allows quantitative interpretation of
      cellular regulatory events from population data, and it is a valuable approach
      for investigating novel aspects of eQTL data sets.

PMID- 29021292
TI  - Metabolite Profiling Reveals the Glutathione Biosynthetic Pathway as a
      Therapeutic Target in Triple-Negative Breast Cancer.
AB  - Cancer cells can exhibit altered dependency on specific metabolic pathways and
      targeting these dependencies is a promising therapeutic strategy. Triple-negative
      breast cancer (TNBC) is an aggressive and genomically heterogeneous subset of
      breast cancer that is resistant to existing targeted therapies. To identify
      metabolic pathway dependencies in TNBC, we first conducted mass spectrometry
      based metabolomics of TNBC and control cells. Relative levels of intracellular
      metabolites distinguished TNBC from nontransformed breast epithelia and revealed
      two metabolic subtypes within TNBC that correlate with markers of basal-like
      versus non-basal-like status. Among the distinguishing metabolites, levels of the
      cellular redox buffer glutathione were lower in TNBC cell lines compared to
      controls and markedly lower in non-basal-like TNBC. Significantly, these cell
      lines showed enhanced sensitivity to pharmacologic inhibition of glutathione
      biosynthesis that was rescued by N-acetylcysteine, demonstrating a dependence on
      glutathione production to suppress ROS and support tumor cell survival.
      Consistent with this, patients whose tumors express elevated levels of gamma
      glutamylcysteine ligase, the rate-limiting enzyme in glutathione biosynthesis,
      had significantly poorer survival. We find, further, that agents that limit the
      availability of glutathione precursors enhance both glutathione depletion and
      TNBC cell killing by gamma-glutamylcysteine ligase inhibitors in vitro
      Importantly, we demonstrate the ability to this approach to suppress glutathione
      levels and TNBC xenograft growth in vivo Overall, these findings support the
      potential of targeting the glutathione biosynthetic pathway as a therapeutic
      strategy in TNBC and identify the non-basal-like subset as most likely to
      respond. Mol Cancer Ther; 17(1); 264-75. (c)2017 AACR.

PMID- 29021291
TI  - A genome-wide interactome of DNA-associated proteins in the human liver.
AB  - Large-scale efforts like the ENCODE Project have made tremendous progress in
      cataloging the genomic binding patterns of DNA-associated proteins (DAPs), such
      as transcription factors (TFs). However, most chromatin immunoprecipitation
      sequencing (ChIP-seq) analyses have focused on a few immortalized cell lines
      whose activities and physiology differ in important ways from endogenous cells
      and tissues. Consequently, binding data from primary human tissue are essential
      to improving our understanding of in vivo gene regulation. Here, we identify and
      analyze more than 440,000 binding sites using ChIP-seq data for 20 DAPs in two
      human liver tissue samples. We integrated binding data with transcriptome and
      phased WGS data to investigate allelic DAP interactions and the impact of
      heterozygous sequence variation on the expression of neighboring genes. Our
      tissue-based data set exhibits binding patterns more consistent with liver
      biology than cell lines, and we describe uses of these data to better prioritize
      impactful noncoding variation. Collectively, our rich data set offers novel
      insights into genome function in human liver tissue and provides a valuable
      resource for assessing disease-related disruptions.

PMID- 29021294
TI  - Identification of Serological Biomarkers for Early Diagnosis of Lung Cancer Using
      a Protein Array-Based Approach.
AB  - Lung cancer (LC) remains the leading cause of mortality from malignant tumors
      worldwide. Currently, a lack of serological biomarkers for early LC diagnosis is
      a major roadblock for early intervention and prevention of LC. To undertake this
      challenge, we employed a two-phase strategy to discover and validate a biomarker
      panel using a protein array-based approach. In Phase I, we obtained serological
      autoimmune profiles of 80 LC patients and 20 healthy subjects on HuProt arrays,
      and identified 170 candidate proteins significantly associated with LC. In Phase
      II, we constructed a LC focused array with the 170 proteins, and profiled a large
      cohort, comprised of 352 LC patients, 93 healthy individuals, and 101 patients
      with lung benign lesions (LBL). The comparison of autoimmune profiles between the
      early stage LC and the combined group of healthy and LBL allowed us to identify
      and validate a biomarker panel of p53, HRas, and ETHE1 for diagnosis of early
      stage LC with 50% sensitivity at >90% specificity. Finally, the performance of
      this biomarker panel was confirmed in ELISA tests. In summary, this study
      represents one of the most comprehensive proteome-wide surveys with one of the
      largest (i.e. 1,101 unique samples) and most diverse (i.e. nine disease groups)
      cohorts, resulting in a biomarker panel with good performance.

PMID- 29021293
TI  - PPARgamma Ligand-induced Annexin A1 Expression Determines Chemotherapy Response
      via Deubiquitination of Death Domain Kinase RIP in Triple-negative Breast
      Cancers.
AB  - Metastatic breast cancer is still incurable so far; new specifically targeted and
      more effective therapies for triple-negative breast cancer (TNBC) are required in
      the clinic. In this study, our clinical data have established that basal and
      claudin-low subtypes of breast cancer (TNBC types) express significantly higher
      levels of Annexin A1 (ANXA1) with poor survival outcomes. Using human cancer cell
      lines that model the TNBC subtype, we observed a strong positive correlation
      between expression of ANXA1 and PPARgamma. A similar correlation between these
      two markers was also established in our clinical breast cancer patients'
      specimens. To establish a link between these two markers in TNBC, we show de novo
      expression of ANXA1 is induced by activation of PPARgamma both in vitro and in
      vivo and it has a predictive value in determining chemosensitivity to PPARgamma
      ligands. Mechanistically, we show for the first time PPARgamma-induced ANXA1
      protein directly interacts with receptor interacting protein-1 (RIP1), promoting
      its deubiquitination and thereby activating the caspase-8-dependent death
      pathway. We further identified this underlying mechanism also involved a
      PPARgamma-induced ANXA1-dependent autoubiquitination of cIAP1, the direct E3
      ligase of RIP1, shifting cIAP1 toward proteosomal degradation. Collectively, our
      study provides first insight for the suitability of using drug-induced expression
      of ANXA1 as a new player in RIP1-induced death machinery in TNBCs, presenting
      itself both as an inclusion criterion for patient selection and surrogate marker
      for drug response in future PPARgamma chemotherapy trials. Mol Cancer Ther;
      16(11); 2528-42. (c)2017 AACR.

PMID- 29021288
TI  - Co-expression networks reveal the tissue-specific regulation of transcription and
      splicing.
AB  - Gene co-expression networks capture biologically important patterns in gene
      expression data, enabling functional analyses of genes, discovery of biomarkers,
      and interpretation of genetic variants. Most network analyses to date have been
      limited to assessing correlation between total gene expression levels in a single
      tissue or small sets of tissues. Here, we built networks that additionally
      capture the regulation of relative isoform abundance and splicing, along with
      tissue-specific connections unique to each of a diverse set of tissues. We used
      the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50
      tissues and 449 individuals. First, we developed a framework called Transcriptome
      Wide Networks (TWNs) for combining total expression and relative isoform levels
      into a single sparse network, capturing the interplay between the regulation of
      splicing and transcription. We built TWNs for 16 tissues and found that hubs in
      these networks were strongly enriched for splicing and RNA binding genes,
      demonstrating their utility in unraveling regulation of splicing in the human
      transcriptome. Next, we used a Bayesian biclustering model that identifies
      network edges unique to a single tissue to reconstruct Tissue-Specific Networks
      (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we
      found genetic variants associated with pairs of adjacent nodes in our networks,
      supporting the estimated network structures and identifying 20 genetic variants
      with distant regulatory impact on transcription and splicing. Our networks
      provide an improved understanding of the complex relationships of the human
      transcriptome across tissues.

PMID- 29021295
TI  - Mitochondrial Cardiomyopathy Caused by Elevated Reactive Oxygen Species and
      Impaired Cardiomyocyte Proliferation.
AB  - RATIONALE: Although mitochondrial diseases often cause abnormal myocardial
      development, the mechanisms by which mitochondria influence heart growth and
      function are poorly understood. OBJECTIVE: To investigate these disease
      mechanisms, we studied a genetic model of mitochondrial dysfunction caused by
      inactivation of Tfam (transcription factor A, mitochondrial), a nuclear-encoded
      gene that is essential for mitochondrial gene transcription and mitochondrial DNA
      replication. METHODS AND RESULTS: Tfam inactivation by Nkx2.5Cre caused
      mitochondrial dysfunction and embryonic lethal myocardial hypoplasia. Tfam
      inactivation was accompanied by elevated production of reactive oxygen species
      (ROS) and reduced cardiomyocyte proliferation. Mosaic embryonic Tfam inactivation
      confirmed that the block to cardiomyocyte proliferation was cell autonomous.
      Transcriptional profiling by RNA-seq demonstrated the activation of the DNA
      damage pathway. Pharmacological inhibition of ROS or the DNA damage response
      pathway restored cardiomyocyte proliferation in cultured fetal cardiomyocytes.
      Neonatal Tfam inactivation by AAV9-cTnT-Cre caused progressive, lethal dilated
      cardiomyopathy. Remarkably, postnatal Tfam inactivation and disruption of
      mitochondrial function did not impair cardiomyocyte maturation. Rather, it
      elevated ROS production, activated the DNA damage response pathway, and decreased
      cardiomyocyte proliferation. We identified a transient window during the first
      postnatal week when inhibition of ROS or the DNA damage response pathway
      ameliorated the detrimental effect of Tfam inactivation. CONCLUSIONS:
      Mitochondrial dysfunction caused by Tfam inactivation induced ROS production,
      activated the DNA damage response, and caused cardiomyocyte cell cycle arrest,
      ultimately resulting in lethal cardiomyopathy. Normal mitochondrial function was
      not required for cardiomyocyte maturation. Pharmacological inhibition of ROS or
      DNA damage response pathways is a potential strategy to prevent cardiac
      dysfunction caused by some forms of mitochondrial dysfunction.

PMID- 29021296
TI  - Lactate Promotes Synthetic Phenotype in Vascular Smooth Muscle Cells.
AB  - RATIONALE: The phenotypes of vascular smooth muscle cells (vSMCs) comprise a
      continuum bounded by predominantly contractile and synthetic cells. Some evidence
      suggests that contractile vSMCs can assume a more synthetic phenotype in response
      to ischemic injury, but the mechanisms that activate this phenotypic switch are
      poorly understood. OBJECTIVE: To determine whether lactate, which increases in
      response to regional ischemia, may promote the synthetic phenotype in vSMCs.
      METHODS AND RESULTS: Experiments were performed with vSMCs that had been
      differentiated from human induced pluripotent stem cells and then cultured in
      glucose-free, lactate-enriched (L+) medium or in standard (L-) medium. Compared
      with the L- medium, the L+ medium was associated with significant increases in
      synthetic vSMC marker expression, proliferation, and migration and with
      significant declines in contractile and apoptotic activity. Furthermore, these
      changes were accompanied by increases in the expression of monocarboxylic acid
      transporters and were generally attenuated both by the blockade of monocarboxylic
      acid transporter activity and by transfection with iRNA for NDRG (N-myc
      downstream regulated gene). Proteomics, biomarker, and pathway analyses suggested
      that the L+ medium tended to upregulate the expression of synthetic vSMC markers,
      the production of extracellular proteins that participate in tissue construction
      or repair, and the activity of pathways that regulate cell proliferation and
      migration. Observations in hypoxia-cultured vSMCs were similar to those in L+
      cultured vSMCs, and assessments in a swine myocardial infarction model suggested
      that measurements of lactate levels, lactate-dehydrogenase levels, vSMC
      proliferation, and monocarboxylic acid transporter and NDRG expression were
      greater in the ischemic zone than in nonischemic tissues. CONCLUSIONS: These
      results demonstrate for the first time that vSMCs assume a more synthetic
      phenotype in a microenvironment that is rich in lactate. Thus, mechanisms that
      link glucose metabolism to vSMC phenotypic switching could play a role in the
      pathogenesis and treatment of cardiovascular disease.

PMID- 29021290
TI  - Identifying cis-mediators for trans-eQTLs across many human tissues using genomic
      mediation analysis.
AB  - The impact of inherited genetic variation on gene expression in humans is well
      established. The majority of known expression quantitative trait loci (eQTLs)
      impact expression of local genes (cis-eQTLs). More research is needed to identify
      effects of genetic variation on distant genes (trans-eQTLs) and understand their
      biological mechanisms. One common trans-eQTLs mechanism is "mediation" by a local
      (cis) transcript. Thus, mediation analysis can be applied to genome-wide SNP and
      expression data in order to identify transcripts that are "cis-mediators" of
      trans-eQTLs, including those "cis-hubs" involved in regulation of many trans
      genes. Identifying such mediators helps us understand regulatory networks and
      suggests biological mechanisms underlying trans-eQTLs, both of which are relevant
      for understanding susceptibility to complex diseases. The multitissue expression
      data from the Genotype-Tissue Expression (GTEx) program provides a unique
      opportunity to study cis-mediation across human tissue types. However, the
      presence of complex hidden confounding effects in biological systems can make
      mediation analyses challenging and prone to confounding bias, particularly when
      conducted among diverse samples. To address this problem, we propose a new
      method: Genomic Mediation analysis with Adaptive Confounding adjustment (GMAC).
      It enables the search of a very large pool of variables, and adaptively selects
      potential confounding variables for each mediation test. Analyses of simulated
      data and GTEx data demonstrate that the adaptive selection of confounders by GMAC
      improves the power and precision of mediation analysis. Application of GMAC to
      GTEx data provides new insights into the observed patterns of cis-hubs and trans
      eQTL regulation across tissue types.

PMID- 29021299
TI  - A randomized, placebo-controlled, double-blind Phase 2 trial comparing the
      reactogenicity and immunogenicity of a single >=2x108 colony forming units [cfu]
      standard-dose versus a >=2x109 cfu high-dose of CVD 103-HgR live attenuated oral
      cholera vaccine, with Shanchol inactivated oral vaccine as an open label
      immunologic comparator.
AB  - Reactive immunization with a single-dose cholera vaccine that could rapidly
      (within days) protect immunologically-naive individuals during "virgin soil"
      epidemics would facilitate cholera control. One dose of attenuated Vibrio
      cholerae O1 classical Inaba vaccine CVD 103-HgR (VaxchoraTM) containing >=2x108
      colony forming units (cfu) induces vibriocidal antibody seroconversion (correlate
      of protection) in >90% of U.S. adults. A previous CVD 103-HgR commercial
      formulation required >=2x109 cfu to elicit high seroconversion in developing
      country populations. We compared vibriocidal responses of Malians (18-45 years
      old) randomized to ingest a single >=2x108 cfu standard-dose (N=50) or >=2x109
      cfu high-dose (N=50) of PaxVax CVD 103-HgR with buffer, or two doses (N=50) of
      ShancholTM inactivated cholera vaccine (the immunologic comparator). To maintain
      blinding, participants were dosed twice, 2 weeks apart; CVD 103-HgR recipients
      ingested placebo 2 weeks before or after ingesting vaccine. Seroconversion (>=4
      fold vibriocidal titer rise) between baseline and 14 days after CVD 103-HgR, and
      following the first and second dose of Shanchol were the main outcomes measured.
      By day 14 post-vaccination, seroconversion after a single standard-dose of CVD
      103-HgR was 71.7% (33/46) and 83.3% (40/48) after high-dose. Seroconversion
      following first-dose Shanchol 56.0% (28/50) was significantly lower compared with
      high-dose CVD 103-HgR (p=0.003). High-dose CVD 103-HgR vibriocidal geometric mean
      titer (GMT) exceeded standard-dose GMT at day 14 (214 vs 95, p=0.045) and was ~2
      fold higher than day 7 and day 14 GMT following the first Shanchol dose (p>0.05).
      High-dose CVD 103-HgR is recommended for accelerated evaluation in developing
      countries to assess efficacy and practicality in field situations.

PMID- 29021297
TI  - Parkinson's Disease Is Not Simply a Prion Disorder.
AB  - The notion that prion-like spreading of misfolded alpha-synuclein (alpha-SYN)
      causes Parkinson's disease (PD) has received a great deal of attention. Although
      attractive in its simplicity, the hypothesis is difficult to reconcile with
      postmortem analysis of human brains and connectome-mapping studies. An
      alternative hypothesis is that PD pathology is governed by regional or cell
      autonomous factors. Although these factors provide an explanation for the pattern
      of neuronal loss in PD, they do not readily explain the apparently staged
      distribution of Lewy pathology in many PD brains, the feature of the disease that
      initially motivated the spreading hypothesis by Braak and colleagues. While each
      hypothesis alone has its shortcomings, a synthesis of the two can explain much of
      what we know about the etiopathology of PD.Dual Perspectives Companion Paper:
      Prying into the Prion Hypothesis for Parkinson's Disease, by Patrik Brundin and
      Ronald Melki.

PMID- 29021300
TI  - High-Resolution Epitope Positioning of a Large Collection of Neutralizing and
      Nonneutralizing Single-Domain Antibodies on the Enzymatic and Binding Subunits of
      Ricin Toxin.
AB  - We previously produced a heavy-chain-only antibody (Ab) VH domain (VHH)-displayed
      phage library from two alpacas that had been immunized with ricin toxoid and
      nontoxic mixtures of the enzymatic ricin toxin A subunit (RTA) and binding ricin
      toxin B subunit (RTB) (D. J. Vance, J. M. Tremblay, N. J. Mantis, and C. B.
      Shoemaker, J Biol Chem 288:36538-36547, 2013,
      https://doi.org/10.1074/jbc.M113.519207). Initial and subsequent screens of that
      library by direct enzyme-linked immunosorbent assay (ELISA) yielded more than two
      dozen unique RTA- and RTB-specific VHHs, including 10 whose structures were
      subsequently solved in complex with RTA. To generate a more complete antigenic
      map of ricin toxin and to define the epitopes associated with toxin-neutralizing
      activity, we subjected the VHH-displayed phage library to additional "pannings"
      on both receptor-bound ricin and antibody-captured ricin. We now report the full
      length DNA sequences, binding affinities, and neutralizing activities of 68
      unique VHHs: 31 against RTA, 33 against RTB, and 4 against ricin holotoxin.
      Epitope positioning was achieved through cross-competition ELISAs performed with
      a panel of monoclonal antibodies (MAbs) and verified, in some instances, with
      hydrogen-deuterium exchange mass spectrometry. The 68 VHHs grouped into more than
      20 different competition bins. The RTA-specific VHHs with strong toxin
      neutralizing activities were confined to bins that overlapped two previously
      identified neutralizing hot spots, termed clusters I and II. The four RTB
      specific VHHs with potent toxin-neutralizing activity grouped within three
      adjacent bins situated at the RTA-RTB interface near cluster II. These results
      provide important insights into epitope interrelationships on the surface of
      ricin and delineate regions of vulnerability that can be exploited for the
      purpose of vaccine and therapeutic development.

PMID- 29021301
TI  - Recent Approaches To Optimize Laboratory Assessment of Antinuclear Antibodies.
AB  - The presence of antinuclear antibodies (ANAs) is a hallmark of a number of
      systemic autoimmune rheumatic diseases, and testing is usually performed as part
      of the initial diagnostic workup when suspicion of an underlying autoimmune
      disorder is high. The indirect immunofluorescence antibody (IFA) technique is the
      preferred method for detecting ANAs, as it demonstrates binding to specific
      intracellular structures within the cells, resulting in a number of staining
      patterns that are usually categorized based on the cellular components recognized
      and the degree of binding, as reflected by the fluorescence intensity or titer.
      As a screening tool, the ANA patterns can guide confirmatory testing useful in
      elucidating a specific clinical diagnosis or prognosis. However, routine use of
      ANA IFA testing as a global screening test is hampered by its labor
      intensiveness, subjectivity, and limited diagnostic specificity, among other
      factors. This review focuses on current efforts to standardize the nomenclature
      of ANA patterns and on alternative methods for ANA determination, as well as on
      recent advances in image-based computer algorithms to automate IFA testing in
      clinical laboratories.

PMID- 29021302
TI  - Development of a High-Throughput Respiratory Syncytial Virus Fluorescent Focus
      Based Microneutralization Assay.
AB  - Neutralizing antibodies specific for respiratory syncytial virus (RSV) represent
      a major protective mechanism against RSV infection, as demonstrated by the
      efficacy of the immune-prophylactic monoclonal antibody palivizumab in preventing
      RSV-associated lower respiratory tract infections in premature infants.
      Accordingly, the RSV neutralization assay has become a key functional method to
      assess the neutralizing activity of serum antibodies in preclinical animal
      models, epidemiology studies, and clinical trials. In this study, we qualified a
      24-h, fluorescent focus-based microneutralization (RSVA FFA-MN) method that
      requires no medium exchange or pre- or postinfection processing to detect green
      fluorescent protein-expressing RSV strain A2 (RSVA-GFP)-infected cells, using a
      high-content imaging system for automated image acquisition and focus
      enumeration. The RSVA FFA-MN method was shown to be sensitive, with a limit of
      detection (LOD) and limit of quantitation (LOQ) of 1:10, or 3.32 log2; linear
      over a range of 4.27 to 9.65 log2 50% inhibitory concentration (IC50); and
      precise, with intra- and interassay coefficients of variation of <21%. This
      precision allowed the choice of a statistically justified 3-fold-rise
      seroresponse cutoff criterion. The repeatability and robustness of this method
      were demonstrated by including a pooled human serum sample in every assay as a
      positive control (PC). Over 3 years of testing between two laboratories, this PC
      generated data falling within 2.5 standard deviations of the mean 98.7% of the
      time (n = 1,720). This high-throughput and reliable RSV microneutralization assay
      has proven useful for testing sera from preclinical vaccine candidate evaluation
      studies, epidemiology studies, and both pediatric and adult vaccine clinical
      trials.

PMID- 29021298
TI  - Prying into the Prion Hypothesis for Parkinson's Disease.
AB  - In Parkinson's disease, intracellular alpha-synuclein inclusions form in neurons.
      We suggest that prion-like behavior of alpha-synuclein is a key component in
      Parkinson's disease pathogenesis. Although multiple molecular changes are
      involved in the triggering of the disease process, we propose that neuron-to
      neuron transfer is a crucial event that is essential for Lewy pathology to spread
      from one brain region to another. In this review, we describe key findings in
      human postmortem brains, cultured cells, and animal models of disease that
      support the idea that alpha-synuclein can act as a prion. We consider potential
      triggers of the alpha-synuclein misfolding and why the aggregates escape cellular
      degradation under disease conditions. We also discuss whether different strains
      of alpha-synuclein fibrils can underlie differences in cellular and regional
      distribution of aggregates in different synucleinopathies. Our conclusion is that
      alpha-synuclein probably acts as a prion in human diseases, and a deeper
      understanding of this step in the pathogenesis of Parkinson's disease can
      facilitate the development of disease-modifying therapies in the future.Dual
      Perspectives Companion Paper: Parkinson's Disease Is Not Simply a Prion Disorder,
      by D. James Surmeier, Jose A. Obeso, and Glenda M. Halliday.

PMID- 29021303
TI  - A Single Intramuscular Dose of a Plant-Made Virus-Like Particle Vaccine Elicits a
      Balanced Humoral and Cellular Response and Protects Young and Aged Mice from
      Influenza H1N1 Virus Challenge despite a Modest/Absent Humoral Response.
AB  - Virus-like-particle (VLP) influenza vaccines can be given intramuscularly (i.m.)
      or intranasally (i.n.) and may have advantages over split-virion formulations in
      the elderly. We tested a plant-made VLP vaccine candidate bearing the viral
      hemagglutinin (HA) delivered either i.m. or i.n. in young and aged mice. Young
      adult (5- to 8-week-old) and aged (16- to 20-month-old) female BALB/c mice
      received a single 3-MUg dose based on the HA (A/California/07/2009 H1N1) content
      of a plant-made H1-VLP (i.m. or i.n.) split-virion vaccine (i.m.) or were left
      naive. After vaccination, humoral and splenocyte responses were assessed, and
      some mice were challenged. Both VLP and split vaccines given i.m. protected 100%
      of the young animals, but the VLP group lost the least weight and had stronger
      humoral and cellular responses. Compared to split-vaccine recipients, aged
      animals vaccinated i.m. with VLP were more likely to survive challenge (80%
      versus 60%). The lung viral load postchallenge was lowest in the VLP i.m. groups.
      Mice vaccinated with VLP i.n. had little detectable immune response, but survival
      was significantly increased. In both age groups, i.m. administration of the H1
      VLP vaccine elicited more balanced humoral and cellular responses and provided
      better protection from homologous challenge than the split-virion vaccine.

PMID- 29021307
TI  - Commercially Available Human-Induced Pluripotent Stem Cell-Derived
      Cardiomyocytes: Another Piece in Our Tool Box, but Not a Swiss Army Knife Yet.

PMID- 29021306
TI  - Characterization of a Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte
      Model for the Study of Variant Pathogenicity: Validation of a KCNJ2 Mutation.
AB  - BACKGROUND: Long-QT syndrome is a potentially fatal condition for which 30% of
      patients are without a genetically confirmed diagnosis. Rapid identification of
      causal mutations is thus a priority to avoid at-risk situations that can lead to
      fatal cardiac events. Massively parallel sequencing technologies are useful for
      the identification of sequence variants; however, electrophysiological testing of
      newly identified variants is crucial to demonstrate causality. Long-QT syndrome
      could, therefore, benefit from having a standardized platform for functional
      characterization of candidate variants in the physiological context of human
      cardiomyocytes. METHODS AND RESULTS: Using a variant in Kir2.1 (Gly52Val)
      revealed by whole-exome sequencing in a patient presenting with symptoms of long
      QT syndrome as a proof of principle, we demonstrated that commercially available
      human induced pluripotent stem cell-derived cardiomyocytes are a powerful model
      for screening variants involved in genetic cardiac diseases. Immunohistochemistry
      experiments and whole-cell current recordings in human embryonic kidney cells
      expressing the wild-type or the mutant Kir2.1 demonstrated that Kir2.1-52V alters
      channel cellular trafficking and fails to form a functional channel. Using human
      induced pluripotent stem cell-derived cardiomyocytes, we not only confirmed these
      results but also further demonstrated that Kir2.1-52V is associated with a
      dramatic prolongation of action potential duration with evidence of arrhythmic
      activity, parameters which could not have been studied using human embryonic
      kidney cells. CONCLUSIONS: Our study confirms the pathogenicity of Kir2.1-52V in
      1 patient with long-QT syndrome and also supports the use of isogenic human
      induced pluripotent stem cell-derived cardiomyocytes as a physiologically
      relevant model for the screening of variants of unknown function.

PMID- 29021304
TI  - Kinetics, Longevity, and Cross-Reactivity of Antineuraminidase Antibody after
      Natural Infection with Influenza A Viruses.
AB  - The kinetics, longevity, and breadth of antibodies to influenza virus
      neuraminidase (NA) in archival, sequential serum/plasma samples from influenza A
      virus (IAV) H5N1 infection survivors and from patients infected with the 2009
      pandemic IAV (H1N1) virus were determined using an enzyme-linked lectin-based
      assay. The reverse-genetics-derived H4N1 viruses harboring a hemagglutinin (HA)
      segment from A/duck/Shan Tou/461/2000 (H4N9) and an NA segment derived from
      either IAV H5N1 clade 1, IAV H5N1 clade 2.3.4, the 2009 pandemic IAV (H1N1)
      (H1N1pdm), or A/Puerto Rico/8/1934 (H1N1) virus were used as the test antigens.
      These serum/plasma samples were also investigated by microneutralization (MN)
      and/or hemagglutination inhibition (HI) assays. Neuraminidase-inhibiting (NI)
      antibodies against N1 NA of both homologous and heterologous viruses were
      observed in H5N1 survivors and H1N1pdm patients. H5N1 survivors who were never
      exposed to H1N1pdm virus developed NI antibodies to H1N1pdm NA. Seroconversion of
      NI antibodies was observed in 65% of the H1N1pdm patients at day 7 after disease
      onset, but an increase in titer was not observed in serum samples obtained late
      in infection. On the other hand, an increase in seroconversion rate with the HI
      assay was observed in the follow-up series of sera obtained on days 7, 14, 28,
      and 90 after infection. The study also showed that NI antibodies are broadly
      reactive, while MN and HI antibodies are more strain specific.

PMID- 29021305
TI  - Predicting the Functional Impact of KCNQ1 Variants of Unknown Significance.
AB  - BACKGROUND: An emerging standard-of-care for long-QT syndrome uses clinical
      genetic testing to identify genetic variants of the KCNQ1 potassium channel.
      However, interpreting results from genetic testing is confounded by the presence
      of variants of unknown significance for which there is inadequate evidence of
      pathogenicity. METHODS AND RESULTS: In this study, we curated from the literature
      a high-quality set of 107 functionally characterized KCNQ1 variants. Based on
      this data set, we completed a detailed quantitative analysis on the sequence
      conservation patterns of subdomains of KCNQ1 and the distribution of pathogenic
      variants therein. We found that conserved subdomains generally are critical for
      channel function and are enriched with dysfunctional variants. Using this
      experimentally validated data set, we trained a neural network, designated
      Q1VarPred, specifically for predicting the functional impact of KCNQ1 variants of
      unknown significance. The estimated predictive performance of Q1VarPred in terms
      of Matthew's correlation coefficient and area under the receiver operating
      characteristic curve were 0.581 and 0.884, respectively, superior to the
      performance of 8 previous methods tested in parallel. Q1VarPred is publicly
      available as a web server at http://meilerlab.org/q1varpred. CONCLUSIONS:
      Although a plethora of tools are available for making pathogenicity predictions
      over a genome-wide scale, previous tools fail to perform in a robust manner when
      applied to KCNQ1. The contrasting and favorable results for Q1VarPred suggest a
      promising approach, where a machine-learning algorithm is tailored to a specific
      protein target and trained with a functionally validated data set to calibrate
      informatics tools.

PMID- 29021308
TI  - Machine Learning and Rare Variant Adjudication in Type 1 Long QT Syndrome.

PMID- 29021309
TI  - Recurrence risk factors in detachable balloon embolization of traumatic direct
      carotid cavernous fistulas in 188 patients.
AB  - PURPOSE: To investigate the effects of detachable balloons in embolizing
      traumatic carotid cavernous fistulas (TCCFs) and the risk factors for recurrence
      after balloon embolization. MATERIALS AND METHODS: 188 patients with TCCFs were
      enrolled, and clinical, treatment, and follow-up data were analyzed for possible
      risk factors for recurrence after embolization. RESULTS: Among 188 patients, 182
      (96.8%) had successful balloon embolization; 6 patients failed. One balloon was
      used in 94 cases and multiple (two or more) balloons were used in 62 patients. 26
      patients had occlusion of the parent artery whereas the remainder had parent
      artery preservation. Periprocedural complications occurred in 3 patients (1.6%)
      including cerebral embolism in 1 and abducent nerve paralysis in the other 2.
      Immediately following embolization, headache appeared in 92 patients and was
      relieved after 3-5 days with medications. A total of 165 patients (87.8%) had
      follow-up (6 months to 16 years, mean 5 years). 23 (13.9%) patients with internal
      carotid artery preservation had recurrence 1-33 days (mean 11 days) after the
      first embolization and were retreated to complete occlusion. Factors affecting
      recurrence were multiple balloons and residual fistula (p<0.05). Logistic
      regression confirmed the independent factors affecting recurrence were multiple
      balloons (>=2 balloons, OR 7.80, 95% CI 2.28 to 26.73; p=0.001) and residual
      fistula immediately following embolization (OR 10.46, 95% CI 2.99 to 36.5;
      p=0.000). CONCLUSION: The recurrence rate is high in the first month after
      embolization with detachable balloons, and multiple balloons and residual fistula
      are two independent factors affecting recurrence following balloon embolization.

PMID- 29021310
TI  - Embolization of palpebral and orbito-frontal fistulas: technical and anatomical
      considerations in treating high-flow superficial skin lesions with liquid
      embolics.
AB  - The treatment of palpebral and periorbital fistulas may be challenging due to the
      presence of multiple anastomosis with eloquent ophthalmic and intracranial
      vascular territories. Moreover, cosmetic and functional characteristics of this
      area pose unique challenges to open surgical approaches and endovascular therapy.
      We review the advantages and disadvantages of different liquid embolics in
      treating palpebral and periorbital fistulas as we describe three successfully
      treated cases. Moreover, we describe important anatomical landmarks that should
      be considered at the time of treatment of these lesions.

PMID- 29021313
TI  - Periorbital arteriovenous malformations: a word of caution.

PMID- 29021312
TI  - Incompletely obliterated cranial arteriovenous fistulae are safely and
      effectively treated with adjuvant epsilon-aminocaproic acid.
AB  - BACKGROUND: Administration of epsilon-aminocaproic acid (epsilonACA), as adjuvant
      therapy following incompletely embolized cranial dural arteriovenous (dAVFs) and
      direct carotid artery to cavernous sinus fistulae (CCFs), is a strategy to
      promote post-procedural thrombosis. However, the efficacy of epsilonACA to treat
      incompletely obliterated dAVFs and CCFs has not been published. The purpose of
      this study was to determine if administration of epsilonACA following incomplete
      embolization of cranial dAVFs or CCFs was associated with an increased likelihood
      of cure on follow-up imaging compared with patients not given adjuvant
      epsilonACA. METHODS: A retrospective cohort study was performed. All patients who
      underwent treatment of a dAVF or CCF at our institution between 1998 and 2016
      were reviewed (n=262). Patients with residual shunting following the first
      attempted endovascular embolization were included in the analysis (n=52). The
      study groups were those treated with epsilonACA following incomplete obliteration
      of the fistula and those who were not. The primary outcome was obliteration of
      the fistula on initial follow-up imaging. Complication rates between cohorts were
      compared. RESULTS: 20 (38%) patients with incompletely obliterated fistulae were
      treated with adjuvant epsilonACA. A trend towards an improved rate of complete
      obliteration on initial follow-up imaging was observed in the group treated with
      epsilonACA (55% vs 34% in the group not treated with epsilonACA, p=0.14). No
      difference in clinical outcomes or thromboembolic complications was observed
      between the groups. CONCLUSIONS: In summary, these data suggest that
      administration of epsilonACA is a safe adjuvant therapy in the management of
      cranial dAVFs and CCFs that are incompletely treated endovascularly.

PMID- 29021311
TI  - Acute ischemic stroke with tandem lesions: technical endovascular management and
      clinical outcomes from the ESCAPE trial.
AB  - BACKGROUND: Tandem occlusions of the extracranial carotid and intracranial
      carotid or middle cerebral artery have a particularly poor prognosis without
      treatment. Several management strategies have been used with no clear consensus
      recommendations. We examined subjects with tandem occlusions enrolled in the
      ESCAPE trial and their outcomes. METHODS: Data are from the ESCAPE trial.
      Additional data were sought on interventions for each subject. RESULTS: There
      were 54 (17%) subjects with tandem extracranial and intracranial occlusions.
      Patients in the endovascular treatment arm (n=30) were more likely to be younger
      (median age 66 years, p<0.01), male (66.7%, p=0.03), diabetic, and without atrial
      fibrillation. Subjects with tandem occlusions were more likely to have
      intracranial internal carotid artery occlusions than M1 occlusions (p<0.01). Of
      the 30 intervention-arm subjects, 17 (57%) underwent emergency endovascular
      treatment of the extracranial disease, 10 subjects before and seven subjects
      after intracranial thrombectomy. Of the remaining 13 subjects, only four required
      staged carotid revascularization due to persistent severe carotid stenosis; four
      had cervical pseudo-occlusions with no residual stenosis after large distal
      carotid thrombus burden aspiration/retrieval. Outcomes were similar between
      subjects with and without tandem lesions. The use of antithrombotic agents after
      acute carotid artery stenting was variable but no symptomatic intracerebral
      hemorrhage was seen in subjects who underwent emergency endovascular treatment of
      extracranial carotid artery. CONCLUSIONS: Tandem occlusions occurred in one-sixth
      of patients and were treated highly variably within the ESCAPE trial. While
      outcomes were similar, the best method to treat the carotid artery in patients
      with tandem occlusion awaits further randomized data. TRIAL REGISTRATION NUMBER:
      NCT01778335.

PMID- 29021314
TI  - Augmented 3D venous navigation for neuroendovascular procedures.
AB  - BACKGROUND: Endovascular venous access is increasingly used for the treatment of
      many cerebrovascular diseases. The quality of venous roadmapping through arterial
      injection can be problematic because of contrast media dilution, slow flow
      velocity, and unilateral opacification of the venous system. OBJECTIVE: To
      describe our experience with the VesselNavigator (Philips Healthcare, Best, The
      Netherlands) in performing live 3D roadmapping for intracranial venous
      procedures. MATERIAL AND METHODS: Live 3D roadmapping is an image-processing
      technique that allows dynamic roadmapping of vessels with immediate adaptation to
      the C-arm movements without the need for contrast injection. For this purpose, 3D
      MR venography is overlaid on live fluoroscopy images after semiautomatic
      coregistration. The technique was applied to cases of idiopathic venous stenosis
      and arteriovenous fistula. RESULTS: The process of coregistration was performed
      by the principal operator in <5 min, just before the treatment. The accuracy was
      controlled peroperatively and was judged satisfactory. Three illustrative cases
      demonstrate the use of this software for venous navigation and pressure
      measurement (case 1), venous stenting (case 2), and transvenous embolization of a
      carotid-cavernous fistula (case 3). CONCLUSION: Our preliminary experience
      suggests that it is a feasible and safe technique for intracranial venous
      navigation and procedures. The potential lowering of overall radiation dose and
      contrast media use needs to be verified with further studies.

PMID- 29021315
TI  - Individual ant workers show self-control.
AB  - Often, the first option is not the best. Self-control can allow humans and
      animals to improve resource intake under such conditions. Self-control in animals
      is often investigated using intertemporal choice tasks-choosing a smaller reward
      immediately or a larger reward after a delay. However, intertemporal choice tasks
      may underestimate self-control, as test subjects may not fully understand the
      task. Vertebrates show much greater apparent self-control in more natural
      foraging contexts and spatial discounting tasks than in intertemporal choice
      tasks. However, little is still known about self-control in invertebrates. Here,
      we investigate self-control in the black garden ant Lasius niger We confront
      individual workers with a spatial discounting task, offering a high-quality
      reward far from the nest and a poor-quality reward closer to the nest. Most ants
      (69%) successfully ignored the closer, poorer reward in favour of the further,
      better one. However, when both the far and the close rewards were of the same
      quality, most ants (83%) chose the closer feeder, indicating that the ants were
      indeed exercising self-control, as opposed to a fixation on an already known food
      source.

PMID- 29021316
TI  - Maternally transmitted non-bacterial male killer in Drosophila biauraria.
AB  - A maternally inherited, all-female trait is widely found among arthropods, which
      is caused by bacterial endosymbionts such as Wolbachia, Rickettsia, Spiroplasma
      and Cardinium We discovered a single female of Drosophila biauraria, collected
      from Tomakomai, Hokkaido, Japan, that produced all-female offspring. This all
      female trait was maternally inherited in the iso-female line (SP12F) by
      backcrossing with males of a normal line (SP11-20) with a 1 : 1 sex ratio derived
      from the same population. The all-female trait was not affected by tetracycline
      treatment performed for two consecutive generations. However, the microinjection
      of filter-sterilized homogenate of SP12F females into SP11-20 females established
      all-female matrilines. Our data suggest the role of transmissible agents, most
      likely viruses, but not bacteria or protists, as the possible cause of the all
      female phenotype, which is likely to be achieved by killing of male embryos
      because egg hatch rates of SP12F were nearly half those of SP11-20. This is the
      first report in Diptera to demonstrate a maternally inherited virus-like element
      as the cause of the male-killing phenotype in D. biauraria.

PMID- 29021317
TI  - Sensory anatomy of the most aquatic of carnivorans: the Antarctic Ross seal, and
      convergences with other mammals.
AB  - Transitions to and from aquatic life involve transformations in sensory systems.
      The Ross seal, Ommatophoca rossii, offers the chance to investigate the cranio
      sensory anatomy in the most aquatic of all seals. The use of non-invasive
      computed tomography on specimens of this rare animal reveals, relative to other
      species of phocids, a reduction in the diameters of the semicircular canals and
      the parafloccular volume. These features are independent of size effects. These
      transformations parallel those recorded in cetaceans, but these do not extend to
      other morphological features such as the reduction in eye muscles and the length
      of the neck, emphasizing the independence of some traits in convergent evolution
      to aquatic life.

PMID- 29021318
TI  - Salinity-induced phenotypic plasticity in threespine stickleback sperm
      activation.
AB  - Phenotypic expression may be and often is influenced by an organism's
      developmental environment, referred to as phenotypic plasticity. The sperm cells
      of teleosts have been found to be inactive in the seminal plasma and are
      activated by osmotic shock for most fish species, through release in either
      hypertonic (for marine fish) or hypotonic (for freshwater fish) water. If this is
      the case, the regulatory system of sperm mobility should be reversed in salt- and
      freshwater fish. We tested this hypothesis by first activating sperm of salt- and
      freshwater populations of threespine stickleback in salt- and freshwater. The
      sperm from saltwater stickleback could be activated in either salinity, which
      matches the freshwater colonization history of the species, whereas the sperm
      from the freshwater population acted as predicted by the osmotic shock theory and
      was activated in freshwater only. As the freshwater population used here was
      calculated to be thousands of years old, we went on to test whether the trait(s)
      were plastic and sperm from freshwater males still could be activated in
      saltwater after individuals were exposed to saltwater. After raising freshwater
      stickleback in saltwater, we found the mature males to have active sperm in both
      saltwater and freshwater. Further, we also found the sperm of wild-caught
      freshwater stickleback to be active in saltwater after exposing those mature
      males to saltwater for only 2 days. This illustrates that the ability for
      stickleback sperm to be activated in a range of water qualities is an
      environmentally induced plastic trait.

PMID- 29021319
TI  - The purging of deleterious mutations in simple and complex mating environments.
AB  - There is a general expectation that sexual selection should align with natural
      selection to aid the purging of deleterious mutations, yet experiments comparing
      purging under monogamy versus polygamy have provided mixed results. Recent
      studies suggest that this may be because the simplified mating environments used
      in these studies reduce the benefit of sexual selection through males and hamper
      natural selection through females by increasing costs associated with sexual
      conflict. To test the effect of the physical mating environment on purging, we
      use experimental evolution in Drosophila melanogaster to track the frequency of
      four separate deleterious mutations in replicate populations that experience
      polygamy under either a simple or structurally complex mating arena while
      controlling for arena size. Consistent with past results suggesting a greater net
      benefit of polygamy in a complex environment, two of the mutations were purged
      significantly faster in this environment. The other two mutations showed no
      significant difference between environments.

PMID- 29021321
TI  - Association Between Urinary Sodium and Potassium Excretion and Blood Pressure
      Among Adults in the United States: National Health and Nutrition Examination
      Survey, 2014.
AB  - BACKGROUND: Higher levels of sodium and lower levels of potassium intake are
      associated with higher blood pressure. However, the shape and magnitude of these
      associations can vary by study participant characteristics or intake assessment
      method. Twenty-four-hour urinary excretion of sodium and potassium are unaffected
      by recall errors and represent all sources of intake, and were collected for the
      first time in a nationally representative US survey. Our objective was to assess
      the associations of blood pressure and hypertension with 24-hour urinary
      excretion of sodium and potassium among US adults. METHODS: Cross-sectional data
      were obtained from 766 participants age 20 to 69 years with complete blood
      pressure and 24-hour urine collections in the 2014 National Health and Nutrition
      Examination Survey, a nationally representative survey of the US
      noninstitutionalized population. Usual 24-hour urinary electrolyte excretion
      (sodium, potassium, and their ratio) was estimated from <=2 collections on
      nonconsecutive days, adjusting for day-to-day variability in excretion. Outcomes
      included systolic and diastolic blood pressure from the average of 3 measures and
      hypertension status, based on average blood pressure >=140/90 and
      antihypertensive medication use. RESULTS: After multivariable adjustment, each
      1000-mg difference in usual 24-hour sodium excretion was directly associated with
      systolic (4.58 mm Hg; 95% confidence interval [CI], 2.64-6.51) and diastolic
      (2.25 mm Hg; 95% CI, 0.83-3.67) blood pressures. Each 1000-mg difference in
      potassium excretion was inversely associated with systolic blood pressure (-3.72
      mm Hg; 95% CI, -6.01 to -1.42). Each 0.5 U difference in sodium-to-potassium
      ratio was directly associated with systolic blood pressure (1.72 mm Hg; 95% CI,
      0.76-2.68). Hypertension was linearly associated with progressively higher sodium
      and lower potassium excretion; in comparison with the lowest quartile of
      excretion, the adjusted odds of hypertension for the highest quartile was 4.22
      (95% CI, 1.36-13.15) for sodium, and 0.38 (95% CI, 0.17-0.87) for potassium
      (P<0.01 for trends). CONCLUSIONS: These cross-sectional results show a strong
      dose-response association between urinary sodium excretion and blood pressure,
      and an inverse association between urinary potassium excretion and blood
      pressure, in a nationally representative sample of US adults.

PMID- 29021324
TI  - Cerebrospinal Fluid Total Protein Reference Intervals Derived from 20 Years of
      Patient Data.
AB  - BACKGROUND: Reference intervals are vital for interpretation of laboratory
      results. Many existing reference intervals for cerebrospinal fluid total protein
      (CSF-TP) are derived from old literature because of the invasive nature of
      sampling. The objective of this study was to determine reference intervals for
      CSF-TP using available patient data. METHODS: Twenty years of hospital database
      information was mined for previously reported CSF-TP results. Associated
      demographic, laboratory, and clinical diagnosis (International Classification of
      Diseases 9/10 codes) details were extracted. CSF-TP results included 3 different
      analytical platforms: the Siemens Vista 1500, Beckman Lx20, and Roche Hitachi
      917. From an initial data set of 19591 samples, the following exclusion criteria
      were applied: incomplete data, white blood cells (WBCs) >5 * 106/L, red blood
      cells (RBCs) >50 * 106/L, and glucose <2.5 mmol/L. Patient charts were reviewed
      in detail to exclude 60 different conditions for which increases in CSF-TP would
      be expected. A total of 6068 samples were included; 63% of the samples were from
      females. Continuous reference intervals were determined using quantile
      regression. Age- and sex-partitioned intervals were established using the
      quantile regression equation and splitting age-groups into 5-year bins. RESULTS:
      CSF-TP showed a marked age dependence, and males had significantly higher CSF-TP
      than females across all ages. CSF-TP results from the 3 different instruments and
      manufacturers showed small (approximately 0.04 g/L), but statistically
      significant, differences. CSF-TP showed weak, but again statistically
      significant, correlation with WBC and RBC but was independent of serum total
      protein and creatinine. CONCLUSIONS: The age dependence of CSF-TP supports that
      age-partitioned reference intervals will be more accurate than a single cutoff,
      particularly in patients with advancing age.

PMID- 29021322
TI  - Influence of Baseline Diastolic Blood Pressure on Effects of Intensive Compared
      With Standard Blood Pressure Control.
AB  - BACKGROUND: In individuals with a low diastolic blood pressure (DBP), the
      potential benefits or risks of intensive systolic blood pressure (SBP) lowering
      are unclear. METHODS: SPRINT (Systolic Blood Pressure Intervention Trial) was a
      randomized controlled trial that compared the effects of intensive (target <120
      mm Hg) and standard (target <140 mm Hg) SBP control in 9361 older adults with
      high blood pressure at increased risk of cardiovascular disease. The primary
      outcome was a composite of cardiovascular disease events. All-cause death and
      incident chronic kidney disease were secondary outcomes. This post hoc analysis
      examined whether the effects of the SBP intervention differed by baseline DBP.
      RESULTS: Mean baseline SBP and DBP were 139.7+/-15.6 and 78.1+/-11.9 mm Hg,
      respectively. Regardless of the randomized treatment, baseline DBP had a U-shaped
      association with the hazard of the primary cardiovascular disease outcome.
      However, the effects of the intensive SBP intervention on the primary outcome
      were not influenced by baseline DBP level (P for interaction=0.83). The primary
      outcome hazard ratio for intensive versus standard treatment was 0.78 (95%
      confidence interval, 0.57-1.07) in the lowest DBP quintile (mean baseline DBP,
      61+/-5 mm Hg) and 0.74 (95% confidence interval, 0.61-0.90) in the upper 4 DBP
      quintiles (mean baseline DBP, 82+/-9 mm Hg), with an interaction P value of 0.78.
      Results were similar for all-cause death and kidney events. CONCLUSIONS: Low
      baseline DBP was associated with increased risk of cardiovascular disease events,
      but there was no evidence that the benefit of the intensive SBP lowering differed
      by baseline DBP. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov. Unique identifier: NCT01206062.

PMID- 29021326
TI  - Remnant Cholesterol and Myocardial Infarction in Normal Weight, Overweight, and
      Obese Individuals from the Copenhagen General Population Study.
AB  - BACKGROUND: We tested whether high remnant cholesterol is associated with high
      myocardial infarction risk, independent of whether an individual is normal
      weight, overweight, or obese. METHODS: A total of 106216 individuals from the
      Copenhagen General Population Study were followed for up to 11 years, during
      which 1565 experienced a myocardial infarction. Individuals were grouped by
      clinically meaningful remnant cholesterol concentrations of <0.5 mmol/L (19
      mg/dL), 0.5 to 0.99 mmol/L (19-38 mg/dL), 1.0 to 1.49 mmol/L (39-58 mg/dL), and
      >=1.5 mmol/L (58 mg/dL), and by body mass index (BMI) of <18.5 kg/m2
      (underweight), 18.5 to 24.9 kg/m2 (normal weight), 25 to 29.9 kg/m2 (overweight),
      and >=30 kg/m2 (obese). RESULTS: Median calculated remnant cholesterol was 0.40
      mmol/L [interquartile range (IQR), 0.30-0.55 mmol/L] [15 mg/dL (12-21 mg/dL)] for
      underweight, 0.50 mmol/L (IQR, 0.37-0.71 mmol/L) [19 mg/dL (14-27 mg/dL)] for
      normal weight, 0.70 mmol/L (IQR, 0.49-1.00 mmol/L) [27 mg/dL (19-39 mg/dL)] for
      overweight, and 0.85 mmol/L (IQR, 0.61-1.20 mmol/L) [(33 mg/dL (24-46 mg/dL)] for
      obese individuals. On continuous scales, remnant cholesterol was positively
      correlated with BMI until reaching a plateau of approximately 1 mmol/L (39 mg/dL)
      at BMI >35 kg/m2. R2 from an unadjusted linear regression for the correlation
      between calculated remnant cholesterol and BMI was 12%. Stepwise higher remnant
      cholesterol was associated with stepwise higher myocardial infarction risk in a
      similar pattern for normal weight, overweight, and obese individuals. When
      compared with individuals with remnant cholesterol <0.5 mmol/L (19 mg/dL),
      individuals with remnant cholesterol >=1.5 mmol/L (58 mg/dL) had hazard ratios
      for myocardial infarction of 2.0 (95% CI, 1.3-3.2) for normal weight, 1.9 (95%
      CI, 1.4-2.6) for overweight, and 2.3 (95% CI, 1.4-3.5) for obese individuals.
      Directly measured remnant cholesterol increased 0.91 mmol/L (95% CI, 0.89-0.94
      mmol/L) [35 mg/dL (34-36 mg/dL)] per 1 mmol/L (39 mg/dL) increase in calculated
      remnant cholesterol. CONCLUSIONS: Remnant cholesterol and BMI were positively
      correlated; however, high remnant cholesterol was associated with higher
      myocardial infarction risk across the examined BMI subcategories, indicating that
      remnant cholesterol is a risk factor for myocardial infarction independent of
      overweight and obesity.

PMID- 29021327
TI  - Gestational Diabetes Mellitus: Why the Controversy?

PMID- 29021328
TI  - Improving the Specificity of Cardiac Biomarkers-The Early Development of Cardiac
      Troponin I (cTnI) Assays.

PMID- 29021323
TI  - Pathologic Stimulus Determines Lineage Commitment of Cardiac C-kit+ Cells.
AB  - BACKGROUND: Although cardiac c-kit+ cells are being tested in clinical trials,
      the circumstances that determine lineage differentiation of c-kit+ cells in vivo
      are unknown. Recent findings suggest that endogenous cardiac c-kit+ cells rarely
      contribute cardiomyocytes to the adult heart. We assessed whether various
      pathological stimuli differentially affect the eventual cell fates of c-kit+
      cells. METHODS: We used single-cell sequencing and genetic lineage tracing of c
      kit+ cells to determine whether various pathological stimuli would result in
      different fates of c-kit+ cells. RESULTS: Single-cell sequencing of cardiac CD45
      c-kit+ cells showed innate heterogeneity, indicative of the existence of vascular
      and mesenchymal c-kit+ cells in normal hearts. Cardiac pressure overload resulted
      in a modest increase in c-kit-derived cardiomyocytes, with significant increases
      in the numbers of endothelial cells and fibroblasts. Doxorubicin-induced acute
      cardiotoxicity did not increase c-kit-derived endothelial cell fates but instead
      induced cardiomyocyte differentiation. Mechanistically, doxorubicin-induced DNA
      damage in c-kit+ cells resulted in expression of p53. Inhibition of p53 blocked
      cardiomyocyte differentiation in response to doxorubicin, whereas stabilization
      of p53 was sufficient to increase c-kit-derived cardiomyocyte differentiation.
      CONCLUSIONS: These results demonstrate that different pathological stimuli induce
      different cell fates of c-kit+ cells in vivo. Although the overall rate of
      cardiomyocyte formation from c-kit+ cells is still below clinically relevant
      levels, we show that p53 is central to the ability of c-kit+ cells to adopt
      cardiomyocyte fates, which could lead to the development of strategies to
      preferentially generate cardiomyocytes from c-kit+ cells.

PMID- 29021325
TI  - High-Density Lipoprotein Subclasses, Coronary Artery Disease, and Cardiovascular
      Mortality.
AB  - BACKGROUND: The inverse relationship between HDL cholesterol and cardiovascular
      mortality is weakened in coronary artery disease (CAD). We aimed to investigate
      the associations of HDL particle concentrations with cardiovascular mortality and
      the impact of CAD on these associations. We also sought to comparatively evaluate
      HDL cholesterol and HDL particle concentrations in predicting cardiovascular
      mortality. METHODS: Total and subclass HDL particle concentrations were measured
      by nuclear magnetic resonance spectroscopy in 2290 participants of the
      LUdwigshafen RIsk and Cardiovascular Health study referred for coronary
      angiography. The participants were prospectively followed over a median
      (interquartile range) duration of 10.0 (6.1-10.6) years. RESULTS: The mean (SD)
      age of the participants (1575 males, 715 females) was 62.9 (10.4) years; body
      mass index, 27.6 (4.1) kg/m2; HDL cholesterol, 39 (11) mg/dL [1 (0.29) mmol/L];
      and total HDL particle concentration, 24.1 (5.8) MUmol/L. Of the participants,
      434 died from cardiovascular diseases. In multivariate analyses, tertiles of
      total HDL particle concentrations were inversely related to cardiovascular
      mortality (hazard ratio for third vs first tertile = 0.55, P < 0.001). This
      association was primarily mediated by small HDL particles (P < 0.001). Adding
      total or small HDL particle concentrations rather than HDL cholesterol to
      multivariate prediction models improved performance metrics for cardiovascular
      mortality. The presence of CAD had no impact on the associations between HDL
      particle concentrations and cardiovascular mortality. CONCLUSIONS: High HDL
      particle concentration is consistently and independently of CAD associated with
      decreased cardiovascular mortality. Whether the inverse relationship between HDL
      particle concentration and cardiovascular mortality may be translated into novel
      therapies is under investigation.

PMID- 29021329
TI  - Human Chorionic Gonadotropin Assays for Testicular Tumors: Closing the Gap
      between Clinical and Laboratory Practice.
AB  - BACKGROUND: Clinical practice guidelines recommend the measurement of human
      chorionic gonadotropin (hCG) and/or hCGbeta in serum for management of testicular
      germ cell tumors (GCTs). These guidelines, however, disregard relevant
      biochemical information on hCG variants to be detected for oncological
      application. We set out to provide a critical review of the clinical evidence
      together with a characterization of the selectivity of currently marketed hCG
      immunoassays, identifying assays suitable for management of GCTs. CONTENT:
      Evidence sources in the available literature were critically appraised. Most
      instances of misdiagnosis and mismanagement of testicular GCTs have been
      associated with hCG results. According to the clinical evidence, 36% of patients
      with seminoma show an exclusive hCGbeta increase, and 71% of patients with
      nonseminomatous GCTs (NSGCTs) show an increase of intact hCG and/or hCG +
      hCGbeta, whereas the hCGbeta increase in NSGCTs is variable according to the
      tumor stage and histology. SUMMARY: hCG + hCGbeta assays that display an
      equimolar recognition of hCG and hCGbeta, or at least do not overtly
      underestimate hCGbeta, may be employed for management of testicular GCTs. Assays
      that underestimate hCGbeta are not recommended for oncological application. In
      addition to the hCG + hCGbeta assay in service, an additional assay with broader
      selectivity for other hCG variants should be considered when false-negative or
      false-positive results are suspected on the basis of clinical data.

PMID- 29021330
TI  - Response to: The need for incorporating emotional intelligence and mindfulness
      training in modern medical education.

PMID- 29021331
TI  - Correction.

PMID- 29021332
TI  - Statin Discontinuation, Reinitiation, and Persistence Patterns Among Medicare
      Beneficiaries After Myocardial Infarction: A Cohort Study.
AB  - BACKGROUND: Although the benefits of statins accrue over time, treatment
      discontinuation is common. Examining the patterns of statin discontinuation,
      reinitiation, and persistence after reinitiation among Medicare beneficiaries
      after hospital discharge for a myocardial infarction may help increase statin use
      in high-risk patients. METHODS AND RESULTS: Medicare beneficiaries with a statin
      fill claim within 30 days after hospital discharge for myocardial infarction in
      2007 to 2012 (n=158 795) were followed for 182 days post-discharge to identify
      discontinuation, defined as 60 continuous days without statins available.
      Reinitiation, defined by a statin fill, was identified in the 365 days post
      discontinuation. High persistence was defined as proportion of days covered >=80%
      with >=1 day of statin supply 182 days after reinitiation. Follow-up ended on
      December 31, 2014. In the 182 days after myocardial infarction hospital
      discharge, 15.4% of beneficiaries discontinued statins. Of this group, 53.7%
      reinitiated statins. On reinitiation, 27.1% changed statin type, 6.9% up-titrated
      intensity, 14.4% down-titrated intensity, and 66.0% had the same statin and
      intensity. In the 182 days after reinitiation, 45.8% had high persistence.
      Moderate- and high- versus low-intensity statins were associated with a lower
      risk for statin discontinuation (moderate intensity: relative risk [RR], 0.93;
      95% confidence interval [CI], 0.89-0.96; high-intensity: RR, 0.95; 95% CI, 0.91
      0.99). High persistence was less common after reinitiating high- versus low
      intensity statins (RR, 0.80; 95% CI, 0.75-0.86), but no association was present
      for those reinitiating a moderate- versus low-intensity statin (RR, 0.95; 95% CI,
      0.90-1.01). Down-titrating versus reinitiating the same statin intensity (RR,
      1.10; 95% CI, 1.05-1.16) and reinitiating a different versus the same statin (RR,
      1.10; 95% CI, 1.06-1.14) were associated with high persistence after treatment
      reinitiation. CONCLUSIONS: Although many people who discontinue a statin
      reinitiate treatment, statin persistence after reinitiation was low. Reinitiating
      therapy with moderate-intensity statins, down-titration, and using a different
      statin may promote persistence.

PMID- 29021334
TI  - Design and Initial Results of the Minneapolis Heart Institute TeleHeart Program.

PMID- 29021333
TI  - Is Risk-Standardized In-Hospital Stroke Mortality an Adequate Proxy for Risk
      Standardized 30-Day Stroke Mortality Data? Findings From Get With The Guidelines
      Stroke.
AB  - BACKGROUND: Hospital profiling is typically undertaken using risk-standardized 30
      day mortality, but obtaining these data for hospitals can be difficult. We sought
      to determine whether risk-standardized in-hospital mortality could serve as an
      adequate proxy for risk-standardized 30-day mortality data for the purposes of
      identifying outlier hospitals. METHODS AND RESULTS: Acute ischemic stroke cases
      entered into GWTG (Get With The Guidelines)-Stroke between 2003 and 2013 were
      linked to fee-for-service Medicare files to obtain 30-day mortality. Risk
      standardized mortality rates (RSMR) for in-hospital and 30-day mortality were
      generated using previously developed risk score models, and the proportion of
      hospitals classified as statistical outliers compared. We also assessed the
      impact of using the combined outcome of in-hospital mortality or discharge to
      hospice. A total of 535 332 ischemic stroke patients from 1494 GWTG-Stroke
      hospitals were included; mean age was 80 years, 59% female, and 19% nonwhite. At
      the hospital level, mean in-hospital RSMRs and 30-day RSMRs were 6.0% and 14.6%,
      respectively, but the correlation between the 2 was modest (r=0.53). Overall
      agreement in the designation of outlier hospitals between in-hospital and 30-day
      RSMRs was 78%, but chance-corrected agreement was only fair (kappa=0.29).
      However, when using the combined outcome of in-hospital mortality or discharge to
      hospice (risk-standardized mean =11.8%), the correlation with 30-day RSMR was
      much stronger (r= 0.83) and outlier agreement improved substantially
      (kappa=0.60). CONCLUSIONS: When used to identify outlier hospitals with high or
      low mortality, the agreement between risk-standardized in-hospital mortality and
      30-day mortality was modest. However, the combined outcome of in-hospital
      mortality or discharge to hospice showed much better agreement with 30-day
      mortality. This composite outcome could serve as a proxy for 30-day mortality
      when used to identify low- or high-performing hospitals.

PMID- 29021335
TI  - Nonadherence in the Learning Healthcare System: Avoiding a Mountain by Seeing the
      Bumps.

PMID- 29021336
TI  - Pooled Analysis of Multiple Crossover Trials To Optimize Individual Therapy
      Response to Renin-Angiotensin-Aldosterone System Intervention.
AB  - BACKGROUND AND OBJECTIVES: In the treatment of CKD, individual patients show a
      wide variation in their response to many drugs, including renin-angiotensin
      aldosterone system inhibitors (RAASi). To investigate whether therapy resistance
      to RAASi can be overcome by uptitrating the dose of drug, changing the mode of
      intervention (with drugs from similar or different classes), or lowering dietary
      sodium intake, we meta-analyzed individual responses to different modes of
      interventions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Randomized
      crossover trials were analyzed to assess correlation of individual responses to
      RAASi and nonsteroidal anti-inflammatory drugs (NSAIDs; n=395 patients). Included
      studies compared the antialbuminuric effect of uptitrating the dose of RAASi
      (n=10 studies) and NSAIDs (n=1), changing within the same class of RAASi (e.g.,
      angiotensin-converting enzyme inhibition to angiotensin receptor blockers; n=5)
      or NSAIDs (n=1), changing from RAASi to NSAIDs (n=2), and changing from high to
      low sodium intake (n=5). A two-stage meta-analysis was conducted: Deming
      regression was conducted in each study to assess correlations in response, and
      individual study results were then meta-analyzed. RESULTS: The albuminuria
      response to one dose of RAASi or NSAIDs positively correlated with the response
      to a higher dose of the same drug (r=0.72; 95% confidence interval [95% CI], 0.66
      to 0.78), changes within the same class of RAASi or NSAIDs (r=0.54; 95% CI, 0.35
      to 0.68), changes between RAASi and NSAIDs (r=0.44; 95% CI, 0.16 to 0.66), and
      changes from high to moderately low salt intake (r=0.36; 95% CI, 0.22 to 0.48).
      Results were similar when the individual systolic BP and potassium responses were
      analyzed, and were consistent in patients with and without diabetes. CONCLUSIONS:
      Individuals who show a poor response to one dose or type of RAASi also show a
      poor response to higher doses, other types of RAASi or NSAIDs, or a reduction in
      dietary salt intake. Whether other drugs or drug combinations targeting pathways
      beyond the renin-angiotensin-aldosterone system and prostaglandins would improve
      the individual poor response requires further study.

PMID- 29021337
TI  - Involvement of the exomer complex in the polarized transport of Ena1 required for
      Saccharomyces cerevisiae survival against toxic cations.
AB  - Exomer is an adaptor complex required for the direct transport of a selected
      number of cargoes from the trans-Golgi network (TGN) to the plasma membrane in
      Saccharomyces cerevisiae However, exomer mutants are highly sensitive to
      increased concentrations of alkali metal cations, a situation that remains
      unexplained by the lack of transport of any known cargoes. Here we identify
      several HAL genes that act as multicopy suppressors of this sensitivity and are
      connected to the reduced function of the sodium ATPase Ena1. Furthermore, we find
      that Ena1 is dependent on exomer function. Even though Ena1 can reach the plasma
      membrane independently of exomer, polarized delivery of Ena1 to the bud requires
      functional exomer. Moreover, exomer is required for full induction of Ena1
      expression after cationic stress by facilitating the plasma membrane recruitment
      of the molecular machinery involved in Rim101 processing and activation of the
      RIM101 pathway in response to stress. Both the defective localization and the
      reduced levels of Ena1 contribute to the sensitivity of exomer mutants to alkali
      metal cations. Our work thus expands the spectrum of exomer-dependent proteins
      and provides a link to a more general role of exomer in TGN organization.

PMID- 29021338
TI  - A Daple-Akt feed-forward loop enhances noncanonical Wnt signals by
      compartmentalizing beta-catenin.
AB  - Cellular proliferation is antagonistically regulated by canonical and
      noncanonical Wnt signals; their dysbalance triggers cancers. We previously showed
      that a multimodular signal transducer, Daple, enhances PI3-K->Akt signals within
      the noncanonical Wnt signaling pathway and antagonistically inhibits canonical
      Wnt responses. Here we demonstrate that the PI3-K->Akt pathway serves as a
      positive feedback loop that further enhances noncanonical Wnt signals by
      compartmentalizing beta-catenin. By phosphorylating the phosphoinositide- (PI)
      binding domain of Daple, Akt abolishes Daple's ability to bind PI3-P-enriched
      endosomes that engage dynein motor complex for long-distance trafficking of beta
      catenin/E-cadherin complexes to pericentriolar recycling endosomes (PCREs).
      Phosphorylation compartmentalizes Daple/beta-catenin/E-cadherin complexes to cell
      cell contact sites, enhances noncanonical Wnt signals, and thereby suppresses
      colony growth. Dephosphorylation compartmentalizes beta-catenin on PCREs, a
      specialized compartment for prolonged unopposed canonical Wnt signaling, and
      enhances colony growth. Cancer-associated Daple mutants that are insensitive to
      Akt mimic a constitutively dephosphorylated state. This work not only identifies
      Daple as a platform for cross-talk between Akt and the noncanonical Wnt pathway
      but also reveals the impact of such cross-talk on tumor cell phenotypes that are
      critical for cancer initiation and progression.

PMID- 29021340
TI  - Down-regulation of the Wnt/beta-catenin signaling pathway by Cacnb4.
AB  - The beta4 isoform of the beta-subunits of voltage-gated calcium channel regulates
      cell proliferation and cell cycle progression. Herein we show that coexpression
      of the beta4-subunit with actors of the canonical Wnt/beta-catenin signaling
      pathway in a hepatoma cell line inhibits Wnt-responsive gene transcription and
      decreases cell division, in agreement with the role of the Wnt pathway in cell
      proliferation. beta4-subunit-mediated inhibition of Wnt signaling is observed in
      the presence of LiCl, an inhibitor of glycogen synthase kinase (GSK3) that
      promotes beta-catenin translocation to the nucleus. Expression of beta4-subunit
      mutants that lost the ability to translocate to the nucleus has no effect on Wnt
      signaling, suggesting that beta4-subunit inhibition of Wnt signaling occurs
      downstream from GSK3 and requires targeting of beta4-subunit to the nucleus.
      beta4-subunit coimmunoprecipitates with the TCF4 transcription factor and
      overexpression of TCF4 reverses the effect of beta4-subunit on the Wnt pathway.
      We thus propose that the interaction of nuclear beta4-subunit with TCF4 prevents
      beta-catenin binding to TCF4 and leads to the inhibition of the Wnt-responsive
      gene transcription. Thereby, our results show that beta4-subunit is a TCF4
      repressor and therefore appears as an interesting candidate for the regulation of
      this pathway in neurons where beta4-subunit is specifically expressed.

PMID- 29021339
TI  - Phosphorylation regulates connexin43/ZO-1 binding and release, an important step
      in gap junction turnover.
AB  - To investigate whether connexin phosphorylation regulates the known role of
      zonula occludens-1 protein (ZO-1) in gap junction (GJ) function, we generated and
      analyzed a series of phosphomimetic and phosphorylation-dead mutants by mutating
      known conserved regulatory serine (S) residues 255, 279/282, 365, 368, and 373
      located in the C-terminal domain of connexin43 (Cx43) into glutamic acid (E) or
      alanine (A) residues. All connexin mutants were translated into stable, full
      length proteins and assembled into GJs when expressed in HeLa or Madin-Darby
      canine kidney epithelial cells. However, mutants with S residues exchanged at
      positions 365, 368, and 373 exhibited a significantly altered ZO-1 interaction
      profile, while mutants with S residues exchanged at 255 and 279/282 did not.
      Unlike wild-type Cx43, in which ZO-1 binding is restricted to the periphery of GJ
      plaques, S365A, S365E, S368A, S368E, and S373A mutants bound ZO-1 throughout the
      GJ plaques, while the S373E mutant did not bind ZO-1 at all. Inability to
      disengage from ZO-1 correlated with increased GJ plaque size and increased
      connexin protein half-life, while maintaining GJ channels in an open, functional
      state. Quantitative clathrin-binding analyses revealed no significant alterations
      in clathrin-binding efficiency, suggesting that the inability to disengage from
      ZO-1 prevented maturation of functional into nonfunctional/endocytic channels,
      rather than ZO-1 interfering with GJ endocytosis directly. Collectively, our
      results indicate that ZO-1 binding regulates channel accrual, while disengagement
      from ZO-1 is critical for GJ channel closure and transitioning GJ channels for
      endocytosis. Intriguingly, these transitional ZO-1 binding/release and channel
      aging steps are mediated by a series of hierarchical
      phosphorylation/dephosphorylation events at S373, S365, and S368, well-known Cx43
      Akt, protein kinase A, and protein kinase C phosphorylation sites located in the
      vicinity of the ZO-1 binding site.

PMID- 29021342
TI  - Digging deep into Golgi phenotypic diversity with unsupervised machine learning.
AB  - The synthesis of glycans and the sorting of proteins are critical functions of
      the Golgi apparatus and depend on its highly complex and compartmentalized
      architecture. High-content image analysis coupled to RNA interference screening
      offers opportunities to explore this organelle organization and the gene network
      underlying it. To date, image-based Golgi screens have based on a single
      parameter or supervised analysis with predefined Golgi structural classes. Here,
      we report the use of multiparametric data extracted from a single marker and a
      computational unsupervised analysis framework to explore Golgi phenotypic
      diversity more extensively. In contrast with the three visually definable
      phenotypes, our framework reproducibly identified 10 Golgi phenotypes. They were
      used to quantify and stratify phenotypic similarities among genetic
      perturbations. The derived phenotypic network partially overlaps previously
      reported protein-protein interactions as well as suggesting novel functional
      interactions. Our workflow suggests the existence of multiple stable Golgi
      organizational states and provides a proof of concept for the classification of
      drugs and genes using fine-grained phenotypic information.

PMID- 29021341
TI  - Acquisition of cell migration defines NK cell differentiation from hematopoietic
      stem cell precursors.
AB  - Human natural killer (NK) cells are generated from CD34+ precursors and can be
      differentiated in vitro by coculture with developmentally supportive stromal
      cells. We have previously described the acquisition of cell migration as a
      feature of NK cell terminal maturation in this system. Here we perform continuous
      long-term imaging and tracking of NK cell progenitors undergoing in vitro
      differentiation. We demonstrate that NK cell precursors can be tracked over long
      time periods on the order of weeks by utilizing phase-contrast microscopy and
      show that these cells acquire increasing motility as they mature. Additionally,
      we observe that NK cells display a more heterogeneous range of migratory
      behaviors at later stages of development, with the acquisition of complex modes
      of migration that are associated with terminal maturation. Together these data
      demonstrate previously unknown migratory behaviors of innate lymphocytes
      undergoing lineage differentiation revealed by long-term imaging and analysis
      workflows.

PMID- 29021343
TI  - Tubulin isoform composition tunes microtubule dynamics.
AB  - Microtubules polymerize and depolymerize stochastically, a behavior essential for
      cell division, motility, and differentiation. While many studies advanced our
      understanding of how microtubule-associated proteins tune microtubule dynamics in
      trans, we have yet to understand how tubulin genetic diversity regulates
      microtubule functions. The majority of in vitro dynamics studies are performed
      with tubulin purified from brain tissue. This preparation is not representative
      of tubulin found in many cell types. Here we report the 4.2-A cryo-electron
      microscopy (cryo-EM) structure and in vitro dynamics parameters of
      alpha1B/betaI+betaIVb microtubules assembled from tubulin purified from a human
      embryonic kidney cell line with isoform composition characteristic of fibroblasts
      and many immortalized cell lines. We find that these microtubules grow faster and
      transition to depolymerization less frequently compared with brain microtubules.
      Cryo-EM reveals that the dynamic ends of alpha1B/betaI+betaIVb microtubules are
      less tapered and that these tubulin heterodimers display lower curvatures.
      Interestingly, analysis of EB1 distributions at dynamic ends suggests no
      differences in GTP cap sizes. Last, we show that the addition of recombinant
      alpha1A/betaIII tubulin, a neuronal isotype overexpressed in many tumors,
      proportionally tunes the dynamics of alpha1B/betaI+betaIVb microtubules. Our
      study is an important step toward understanding how tubulin isoform composition
      tunes microtubule dynamics.

PMID- 29021346
TI  - The HECT E3 ubiquitin ligase NEDD4 interacts with and ubiquitylates SQSTM1 for
      inclusion body autophagy.
AB  - Our previous studies have shown that the HECT E3 ubiquitin ligase NEDD4 interacts
      with LC3 and is required for starvation and rapamycin-induced activation of
      autophagy. Here, we report that NEDD4 directly binds to SQSTM1 via its HECT
      domain and polyubiquitylates SQSTM1. This ubiquitylation is through K63
      conjugation and is not involved in proteasomal degradation. Mutational analysis
      indicates that NEDD4 interacts with and ubiquitylates the PB1 domain of SQSTM1.
      Depletion of NEDD4 or overexpression of the ligase-defective mutant of NEDD4
      induced accumulation of aberrant enlarged SQSTM1-positive inclusion bodies that
      are co-localized with the endoplasmic reticulum (ER) marker CANX, suggesting that
      the ubiquitylation functions in the SQSTM1-mediated biogenic process in inclusion
      body autophagosomes. Taken together, our studies show that NEDD4 is an autophagic
      E3 ubiquitin ligase that ubiquitylates SQSTM1, facilitating SQSTM1-mediated
      inclusion body autophagy.

PMID- 29021347
TI  - Multiple pathways facilitate the biogenesis of mammalian tail-anchored proteins.
AB  - Tail-anchored (TA) proteins are transmembrane proteins with a single C-terminal
      transmembrane domain, which functions as both their subcellular targeting signal
      and membrane anchor. We show that knockout of TRC40 in cultured human cells has a
      relatively minor effect on endogenous TA proteins, despite their apparent
      reliance on this pathway in vitro These findings support recent evidence that the
      canonical TRC40 pathway is not essential for TA protein biogenesis in vivo We
      therefore investigated the possibility that other ER-targeting routes can
      complement the TRC40 pathway and identified roles for both the SRP pathway and
      the recently described mammalian SND pathway in TA protein biogenesis. We
      conclude that, although TRC40 normally plays an important role in TA protein
      biogenesis, it is not essential, and speculate that alternative pathways for TA
      protein biogenesis, including those identified in this study, contribute to the
      redundancy of the TRC40 pathway.

PMID- 29021345
TI  - Direct evidence of amyloid precursor-like protein 1 trans interactions in cell
      cell adhesion platforms investigated via fluorescence fluctuation spectroscopy.
AB  - The amyloid precursor-like protein 1 (APLP1) is a type I transmembrane protein
      that plays a role in synaptic adhesion and synaptogenesis. Past investigations
      indicated that APLP1 is involved in the formation of protein-protein complexes
      that bridge the junctions between neighboring cells. Nevertheless, APLP1-APLP1
      trans interactions have never been directly observed in higher eukaryotic cells.
      Here, we investigated APLP1 interactions and dynamics directly in living human
      embryonic kidney cells using fluorescence fluctuation spectroscopy techniques,
      namely cross-correlation scanning fluorescence correlation spectroscopy and
      number and brightness analysis. Our results show that APLP1 forms homotypic trans
      complexes at cell-cell contacts. In the presence of zinc ions, the protein forms
      macroscopic clusters, exhibiting an even higher degree of trans binding and
      strongly reduced dynamics. Further evidence from giant plasma membrane vesicles
      suggests that the presence of an intact cortical cytoskeleton is required for
      zinc-induced cis multimerization. Subsequently, large adhesion platforms bridging
      interacting cells are formed through APLP1-APLP1 trans interactions. Taken
      together, our results provide direct evidence that APLP1 functions as a neuronal
      zinc-dependent adhesion protein and allow a more detailed understanding of the
      molecular mechanisms driving the formation of APLP1 adhesion platforms.

PMID- 29021350
TI  - Is the Way to Someone's Heart Through Their Stomach? The Cardiorenal Paradox of
      Incretin-Based Hypoglycemic Drugs in Heart Failure.

PMID- 29021348
TI  - Early Right Ventricular Assist Device Use in Patients Undergoing Continuous-Flow
      Left Ventricular Assist Device Implantation: Incidence and Risk Factors From the
      Interagency Registry for Mechanically Assisted Circulatory Support.
AB  - BACKGROUND: To investigate preimplant risk factors associated with early right
      ventricular assist device (RVAD) use in patients undergoing continuous-flow left
      ventricular assist device (LVAD) surgery. METHODS AND RESULTS: Patients in the
      Interagency Registry for Mechanically Assisted Circulatory Support who underwent
      primary continuous-flow-LVAD surgery were examined for concurrent or subsequent
      RVAD implantation within 14 days of LVAD. Risk factors for RVAD implantation and
      the combined end point of RVAD or death within 14 days of LVAD were assessed with
      stepwise logistic regression. We compared survival between patients with and
      without RVAD using Kaplan-Meier method and Cox proportional hazards modeling. Of
      9976 patients undergoing continuous-flow-LVAD implantation, 386 patients (3.9%)
      required an RVAD within 14 days of LVAD surgery. Preimplant characteristics
      associated with RVAD use included interagency registry for mechanically assisted
      circulatory support patient profiles 1 and 2, the need for preoperative
      extracorporeal membrane oxygenation or renal replacement therapy, severe
      preimplant tricuspid regurgitation, history of cardiac surgery, and concomitant
      procedures other than tricuspid valve repair at the time of LVAD. Hemodynamic
      determinants included elevated right atrial pressure, reduced pulmonary artery
      pulse pressure, and reduced stroke volume. The final model demonstrated good
      performance for both RVAD implant (area under the curve, 0.78) and the combined
      end point of RVAD or death within 14 days (area under the curve, 0.73). Compared
      with patients receiving an isolated LVAD, patients requiring RVAD had decreased 1
      and 6-month survival: 78.1% versus 95.8% and 63.6% versus 87.9%, respectively
      (P<0.0001 for both). CONCLUSIONS: The need for RVAD implantation after LVAD is
      associated with indices of global illness severity, markers of end-organ
      dysfunction, and profiles of hemodynamic instability.

PMID- 29021344
TI  - A microtubule polymerase cooperates with the kinesin-6 motor and a microtubule
      cross-linker to promote bipolar spindle assembly in the absence of kinesin-5 and
      kinesin-14 in fission yeast.
AB  - Accurate chromosome segregation relies on the bipolar mitotic spindle. In many
      eukaryotes, spindle formation is driven by the plus-end-directed motor kinesin-5
      that generates outward force to establish spindle bipolarity. Its inhibition
      leads to the emergence of monopolar spindles with mitotic arrest. Intriguingly,
      simultaneous inactivation of the minus-end-directed motor kinesin-14 restores
      spindle bipolarity in many systems. Here we show that in fission yeast, three
      independent pathways contribute to spindle bipolarity in the absence of kinesin
      5/Cut7 and kinesin-14/Pkl1. One is kinesin-6/Klp9 that engages with spindle
      elongation once short bipolar spindles assemble. Klp9 also ensures the medial
      positioning of anaphase spindles to prevent unequal chromosome segregation.
      Another is the Alp7/TACC-Alp14/TOG microtubule polymerase complex. Temperature
      sensitive alp7cut7pkl1 mutants are arrested with either monopolar or very short
      spindles. Forced targeting of Alp14 to the spindle pole body is sufficient to
      render alp7cut7pkl1 triply deleted cells viable and promote spindle assembly,
      indicating that Alp14-mediated microtubule polymerization from the nuclear face
      of the spindle pole body could generate outward force in place of Cut7 during
      early mitosis. The third pathway involves the Ase1/PRC1 microtubule cross-linker
      that stabilizes antiparallel microtubules. Our study, therefore, unveils
      multifaceted interplay among kinesin-dependent and -independent pathways leading
      to mitotic bipolar spindle assembly.

PMID- 29021352
TI  - Successful motor mapping with transcranial magnetic stimulation in an infant: A
      case report.

PMID- 29021351
TI  - Metabolic Epoxidation Is a Critical Step for the Development of Benzbromarone
      Induced Hepatotoxicity.
AB  - Benzbromarone (BBR) is effective in the treatment of gout; however, clinical
      findings have shown it can also cause fatal hepatic failure. Our early studies
      demonstrated that CYP3A catalyzed the biotransformation of BBR to epoxide
      intermediate(s) that reacted with sulfur nucleophiles of protein to form protein
      covalent binding both in vitro and in vivo. The present study attempted to define
      the correlation between metabolic epoxidation and hepatotoxicity of BBR by
      manipulating the structure of BBR. We rationally designed and synthesized three
      halogenated BBR derivatives, fluorinated BBR (6-F-BBR), chlorinated BBR (6-Cl
      BBR), and brominated BBR (6-Br-BBR), to decrease the potential for cytochrome
      P450-mediated metabolic activation. Both in vitro and in vivo uricosuric activity
      assays showed that 6-F-BBR achieved favorable uricosuric effect, while 6-Cl-BBR
      and 6-Br-BBR showed weak uricosuric efficacy. Additionally, 6-F-BBR elicited much
      lower hepatotoxicity in mice. Fluorination of BBR offered advantage to metabolic
      stability in liver microsomes, almost completely blocked the formation of epoxide
      metabolite(s) and protein covalent binding, and attenuated hepatic and plasma
      glutathione depletion. Moreover, the structural manipulation did not alter the
      efficacy of BBR. This work provided solid evidence that the formation of the
      epoxide(s) is a key step in the development of BBR-induced hepatotoxicity.

PMID- 29021354
TI  - TRMT5 mutations are associated with features of complex hereditary spastic
      paraparesis.

PMID- 29021349
TI  - Activation of Autophagy Ameliorates Cardiomyopathy in Mybpc3-Targeted Knockin
      Mice.
AB  - BACKGROUND: Alterations in autophagy have been reported in hypertrophic
      cardiomyopathy (HCM) caused by Danon disease, Vici syndrome, or LEOPARD syndrome,
      but not in HCM caused by mutations in genes encoding sarcomeric proteins, which
      account for most of HCM cases. MYBPC3, encoding cMyBP-C (cardiac myosin-binding
      protein C), is the most frequently mutated HCM gene. METHODS AND RESULTS: We
      evaluated autophagy in patients with HCM carrying MYBPC3 mutations and in a
      Mybpc3-targeted knockin HCM mouse model, as well as the effect of autophagy
      modulators on the development of cardiomyopathy in knockin mice. Microtubule
      associated protein 1 light chain 3 (LC3)-II protein levels were higher in HCM
      septal myectomies than in nonfailing control hearts and in 60-week-old knockin
      than in wild-type mouse hearts. In contrast to wild-type, autophagic flux was
      blunted and associated with accumulation of residual bodies and glycogen in
      hearts of 60-week-old knockin mice. We found that Akt-mTORC1 (mammalian target of
      rapamycin complex 1) signaling was increased, and treatment with 2.24 mg/kg.d
      rapamycin or 40% caloric restriction for 9 weeks partially rescued cardiomyopathy
      or heart failure and restored autophagic flux in knockin mice. CONCLUSIONS:
      Altogether, we found that (1) autophagy is altered in patients with HCM carrying
      MYBPC3 mutations, (2) autophagy is impaired in Mybpc3-targeted knockin mice, and
      (3) activation of autophagy ameliorated the cardiac disease phenotype in this
      mouse model. We propose that activation of autophagy might be an attractive
      option alone or in combination with another therapy to rescue HCM caused by
      MYBPC3 mutations.

PMID- 29021353
TI  - Longitudinal decline of driving safety in Parkinson disease.
AB  - OBJECTIVE: To longitudinally assess and predict on-road driving safety in
      Parkinson disease (PD). METHODS: Drivers with PD (n = 67) and healthy controls (n
      = 110) drove a standardized route in an instrumented vehicle and were invited to
      return 2 years later. A professional driving expert reviewed drive data and
      videos to score safety errors. RESULTS: At baseline, drivers with PD performed
      worse on visual, cognitive, and motor tests, and committed more road safety
      errors compared to controls (median PD 38.0 vs controls 30.5; p < 0.001). A
      smaller proportion of drivers with PD returned for repeat testing (42.8% vs
      62.7%; p < 0.01). At baseline, returnees with PD made fewer errors than
      nonreturnees with PD (median 34.5 vs 40.0; p < 0.05) and performed similar to
      control returnees (median 33). Baseline global cognitive performance of returnees
      with PD was better than that of nonreturnees with PD, but worse than for control
      returnees (p < 0.05). After 2 years, returnees with PD showed greater cognitive
      decline and larger increase in error counts than control returnees (median
      increase PD 13.5 vs controls 3.0; p < 0.001). Driving error count increase in the
      returnees with PD was predicted by greater error count and worse visual acuity at
      baseline, and by greater interval worsening of global cognition, Unified
      Parkinson's Disease Rating Scale activities of daily living score, executive
      functions, visual processing speed, and attention. CONCLUSIONS: Despite drop out
      of the more impaired drivers within the PD cohort, returning drivers with PD, who
      drove like controls without PD at baseline, showed many more driving safety
      errors than controls after 2 years. Driving decline in PD was predicted by
      baseline driving performance and deterioration of cognitive, visual, and
      functional abnormalities on follow-up.

PMID- 29021355
TI  - Population-based study of home-time by stroke type and correlation with modified
      Rankin score.
AB  - OBJECTIVE: To describe home-time, stratified by stroke type, in a complete
      population and to determine its correlation with modified Rankin Scale (mRS)
      scores. METHODS: We used linked administrative data to derive home-time in all
      patients admitted for a cerebrovascular event in Alberta, Canada, between 2012
      and 2016. Home-time is the number of days spent outside a health institution in
      the first 90 days after index hospitalization. We used negative binomial
      regression, adjusted for age, sex, Charlson comorbidity index, and hospital
      location, to determine the association between home-time and stroke type. In 552
      patients enrolled in 4 acute ischemic stroke clinical trials, we used
      multivariable ordinal logistic regression analysis to determine the association
      between home-time and mRS score at 90 days. RESULTS: Among 15,644 patients (n =
      10,428 with ischemic stroke, n = 1,415 with intracerebral hemorrhage, n = 760
      with subarachnoid hemorrhage, n = 3,041 with TIA), patients with TIA have the
      longest home-time, almost triple the number of days at home compared to patients
      with intracerebral hemorrhage (incidence rate ratio 2.85, 95% confidence interval
      [CI] 2.58-3.15). Among clinical trial ischemic stroke patients, longer home-time
      was associated with a lower mRS score at 90 days (adjusted common odds ratio
      1.04, 95% CI 1.04-1.05). CONCLUSIONS: We showed that home-time is an objective
      and graded indicator that is correlated with disability after stroke. It is
      obtainable from administrative data, applicable to different stroke types, and a
      valuable outcome indicator in population-based health services research.

PMID- 29021357
TI  - Radiographic and symptomatic brain ischemia in CEA and CAS: A systematic review
      and meta-analysis.
AB  - OBJECTIVE: In a systematic review, we compared ratio of new periprocedural
      radiographic brain ischemia (RBI) to the number of strokes and TIAs among
      patients undergoing carotid endarterectomy (CEA) and carotid artery stenting
      (CAS). METHODS: We searched 5 databases for entries related to brain ischemia in
      CEA or CAS from inception through September 2015. We included articles with CEA
      or CAS and systematic performance of preprocedural and postprocedural brain MRI
      and reporting of RBI and stroke incidence. We calculated a symptomatic risk ratio
      of number of strokes and TIAs to RBI. Random effects models were used. RESULTS:
      Fifty-nine studies (5,431 participants) met the inclusion criteria. There were 22
      cohorts in CEA, 34 in CAS with distal protection, 8 in CAS with proximal
      protection, 9 in CAS without protection, and 9 in CAS with unspecified devices.
      Overall, 30.7% (95% confidence interval [CI] 26.6%-34.7%) had RBI, while 3.2%
      (95% CI 2.6%-3.8%) had clinical strokes or TIAs, with a stroke and TIA to RBI
      weighted ratio of 0.18 (95% CI 0.15-0.22). CEA had lower incidence of RBI
      compared to CAS (13.0% vs 37.4%) and also lower number of strokes and TIAs (1.8%
      vs 4.1%). The stroke and TIA to RBI ratio did not differ across 5 different types
      of carotid interventions (p = 0.58). CONCLUSIONS: One in 5 persons with
      periprocedural radiographic brain ischemia during CEA and CAS had strokes and
      TIAs. The stable ratio of stroke and TIA to radiographic ischemia suggests that
      MRI ischemia could serve as a surrogate measure of periprocedural risk.

PMID- 29021358
TI  - Big data trends in stroke epidemiology in the United States: But are they good
      data?

PMID- 29021356
TI  - Volumetric brain changes in migraineurs from the general population.
AB  - OBJECTIVE: To assess volumetric brain changes in migraineurs from the general
      population compared with controls. METHODS: Structural brain changes in
      migraineurs from the general population-based MRI Cerebral Abnormalities in
      Migraine, an Epidemiologic Risk Analysis (CAMERA)-2 observational cohort study
      were assessed by state-of-the-art voxel-based morphometry. T1-weighted MRIs of 84
      migraineurs (52 with aura, 32 without aura) and 35 headache-free controls were
      evaluated. Regional volumes were compared voxelwise, corrected for age, sex, and
      total intracranial volume, with region-of-interest and whole-brain analyses.
      RESULTS: In region-of-interest analyses, migraineurs showed decreased gray matter
      volume in the visual areas V3 and V5 of the right occipital cortex compared to
      controls (p < 0.05, familywise error correction). Post hoc analyses revealed that
      similar changes were present regardless of migraine aura status, disease activity
      (>1 year attack-free [inactive] vs >=1 attack within the last year [active] and
      attack frequency [<=1 (low) vs >=1 attack per month [high]). In exploratory whole
      brain analyses (p < 0.001, uncorrected for multiple comparisons), we identified
      additional structural differences in migraineurs in other cortical and
      subcortical areas, including white matter tracts, that are particularly involved
      in visual processing. CONCLUSIONS: Migraineurs from the general population showed
      small volumetric brain changes, mainly in cortical areas involved in visual
      motion processing, compared to controls. The presence of morphologic changes
      regardless of the presence of migraine aura or disease activity suggests that
      migraines with and without aura share common pathophysiologic pathways and
      suggests that these changes are (partially) irreversible or might have been
      present throughout life.

PMID- 29021360
TI  - Physiology in Perspective: Physiology Provides Insight into Health.

PMID- 29021359
TI  - Increasing prevalence of vascular risk factors in patients with stroke: A call to
      action.
AB  - OBJECTIVE: To evaluate trends in prevalence of cardiovascular risk factors
      (hypertension, diabetes, dyslipidemia, smoking, and drug abuse) and
      cardiovascular diseases (carotid stenosis, chronic renal failure [CRF], and
      coronary artery disease [CAD]) in acute ischemic stroke (AIS) in the United
      States. METHODS: We used the 2004-2014 National Inpatient Sample to compute
      weighted prevalence of each risk factor in hospitalized patients with AIS and
      used joinpoint regression to evaluate change in prevalence over time. RESULTS:
      Across the 2004-2014 period, 92.5% of patients with AIS had >=1 risk factor.
      Overall age- and sex-adjusted prevalence of hypertension, diabetes, dyslipidemia,
      smoking, and drug abuse were 79%, 34%, 47%, 15%, and 2%, respectively, while
      those of carotid stenosis, CRF, and CAD were 13%, 12%, and 27%, respectively.
      Risk factor prevalence varied by age (hypertension: 44% in 18-39 years vs 82% in
      60-79 years), race (diabetes: Hispanic 49% vs white 30%), and sex (drug abuse:
      men 3% vs women 1.4%). Using joinpoint regression, prevalence of hypertension
      increased annually by 1.4%, diabetes by 2%, dyslipidemia by 7%, smoking by 5%,
      and drug abuse by 7%. Prevalence of CRF, carotid stenosis, and CAD increased
      annually by 13%, 6%, and 1%, respectively. Proportion of patients with multiple
      risk factors also increased over time. CONCLUSIONS: Despite numerous guidelines
      and prevention initiatives, prevalence of hypertension, diabetes, dyslipidemia,
      smoking, and drug abuse in AIS increased across the 2004-2014 period. Proportion
      of patients with carotid stenosis, CRF, and multiple risk factors also increased.
      Enhanced risk factor modification strategies and implementation of evidence-based
      recommendations are needed for optimal stroke prevention.

PMID- 29021362
TI  - Chloride Channels Take Center Stage in Acute Regulation of Excitability in
      Skeletal Muscle: Implications for Fatigue.
AB  - Initiation and propagation of action potentials in muscle fibers is a key element
      in the transmission of activating motor input from the central nervous system to
      their contractile apparatus, and maintenance of excitability is therefore
      paramount for their endurance during work. Here, we review current knowledge
      about the acute regulation of ClC-1 channels in active muscles and its importance
      for muscle excitability, function, and fatigue.

PMID- 29021363
TI  - Novel and Unexpected Functions of SGLTs.
AB  - It has been 30 years since the intestinal sodium glucose cotransporter SGLT1 was
      cloned, and, in the intervening years, there have been many advances that have
      influenced physiology and medicine. Among the first was that SGLT1 is the
      founding member of the human gene family SLC5, containing 11 diverse transporters
      and a glucose sensor. Equally surprising was that SGLTs are members of a
      structural family of cotransporters and exchangers in different gene families.
      This led to the conclusion that these proteins operate by a mechanism where
      transport involves the opening and closing of external and internal gates. The
      mechanism is shared by a wide variety of transporters in different structural
      families, e.g., the human facilitated glucose transporters (SLC2) in the huge
      major facilitator superfamily (MFS). Not surprising is the finding that mutations
      in Sglt genes cause the rare diseases glucose-galactose-malabsorption (GGM) and
      familial renal glucosuria (FRG). However, it was not envisaged that SGLT
      inhibitors would be used to treat diabetes mellitus, and these drugs may be able
      to treat cancer. Finally, in 2017, we have just learned that SGLT1 may be
      required to resist infection and to avoid recurrent pregnancy loss.

PMID- 29021361
TI  - Running Changes the Brain: the Long and the Short of It.
AB  - Exercise is a simple intervention that profoundly benefits cognition. In rodents,
      running increases neurogenesis in the hippocampus, a brain area important for
      memory. We describe the dynamic changes in new neuron number and afferent
      connections throughout their maturation. We highlight the effects of exercise on
      the neurotransmitter systems involved, with a focus on the role of glutamate and
      acetylcholine in the initial development of new neurons in the adult brain.

PMID- 29021365
TI  - Lactic Acid: No Longer an Inert and End-Product of Glycolysis.
AB  - For decades, lactic acid has been considered a dead-end product of glycolysis.
      Research in the last 20+ years has shown otherwise. Through its transporters
      (MCTs) and receptor (GPR81), lactic acid plays a key role in multiple cellular
      processes, including energy regulation, immune tolerance, memory formation, wound
      healing, ischemic tissue injury, and cancer growth and metastasis. We summarize
      key findings of lactic acid signaling, functions, and many remaining questions.

PMID- 29021364
TI  - Lymphatic Endothelial Cell Plasticity in Development and Disease.
AB  - The lymphatic vasculature is crucial for maintaining tissue-fluid homeostasis,
      providing immune surveillance and mediating lipid absorption. The lymphatic
      vasculature is tightly associated with the blood vasculature, although it
      exhibits distinct morphological and functional features. Endothelial cells (ECs)
      lineage fate specification is determined during embryonic development; however,
      accumulating evidence suggests that differentiated ECs exhibit remarkable
      heterogeneity and plasticity. In this review, we provide an overview of the
      molecular mechanisms promoting lymphatic cell fate specification in the mammalian
      embryo. We also summarize available data suggesting that lymphatic EC fate is
      reprogrammable in normal and pathological settings. We further discuss the
      possible advantages of cell fate manipulation to treat certain disorders
      associated with lymphatic dysfunction.

PMID- 29021366
TI  - NO donors exhibit anti-inflammatory properties by modulating inflammatory
      signatures and by regulating the life cycle of dendritic cells.
AB  - NO mediates a variety of physiologic processes and is considered an important
      intracellular messenger in different cellular systems. Because of its complex
      regulation and multiple molecular and cellular targets, NO provides both
      stimulatory and suppressive properties in the immune system. Dendritic cells
      (DCs) are considered the most potent APCs, whose regulation has important
      implications in the induction of an effective immune response. In this study, we
      analyzed the effect of the compound NCX 2057, a new class of NO-releasing
      derivatives of ferulic acid, on activation and functional properties of DCs. NCX
      2057 was able to modulate the inflammatory program, the cytokines production, and
      the cellular life cycle but not the maturation markers and the T cells
      stimulatory capacity of DCs in the presence or absence of LPS. The results
      indicate that NCX 2057 may modulate different aspects of the activation of DCs
      and suggest novel applications of NO donors in the contest of inflammatory
      response modulation through the life cycle regulation of DCs.

PMID- 29021369
TI  - New Evidence against Chromium as an Essential Trace Element.
AB  - Nearly 60 y ago, chromium, as the trivalent ion, was proposed to be an essential
      element, but the results of new studies indicate that chromium currently can only
      be considered pharmacologically active and not an essential element. Regardless,
      articles still continue to appear in the literature claiming chromium is an
      essential element. Chromium has been marketed as an agent to reduce body mass and
      develop muscle; however, such marketing claims are no longer allowed in the
      United States because these claims, similar to claims of essential status, are
      not supported by experiments. Trivalent chromium has also been proposed as a
      therapeutic agent to increase insulin sensitivity and affect lipid metabolism.
      Although effective in certain rodent models, beneficial effects in humans have
      not been unequivocally established. Molecular mechanisms have been proposed for
      the beneficial effects but have not been definitively shown to occur in animals.

PMID- 29021367
TI  - Disruption of Trim9 function abrogates macrophage motility in vivo.
AB  - The vertebrate immune response comprises multiple molecular and cellular
      components that interface to provide defense against pathogens. Because of the
      dynamic complexity of the immune system and its interdependent innate and
      adaptive functionality, an understanding of the whole-organism response to
      pathogen exposure remains unresolved. Zebrafish larvae provide a unique model for
      overcoming this obstacle, because larvae are protected against pathogens while
      lacking a functional adaptive immune system during the first few weeks of life.
      Zebrafish larvae were exposed to immune agonists for various lengths of time, and
      a microarray transcriptome analysis was executed. This strategy identified known
      immune response genes, as well as genes with unknown immune function, including
      the E3 ubiquitin ligase tripartite motif-9 (Trim9). Although trim9 expression was
      originally described as "brain specific," its expression has been reported in
      stimulated human Mphis. In this study, we found elevated levels of trim9
      transcripts in vivo in zebrafish Mphis after immune stimulation. Trim9 has been
      implicated in axonal migration, and we therefore investigated the impact of Trim9
      disruption on Mphi motility and found that Mphi chemotaxis and cellular
      architecture are subsequently impaired in vivo. These results demonstrate that
      Trim9 mediates cellular movement and migration in Mphis as well as neurons.

PMID- 29021368
TI  - Spontaneous PMN apoptosis in type 2 diabetes and the impact of periodontitis.
AB  - The purpose of this study was to test the hypothesis that peripheral blood
      neutrophils (PMN) exhibit delayed spontaneous apoptosis in individuals with
      diabetes mellitus type 2 (T2DM) and that the delay is exacerbated further among
      people who coexpress chronic periodontitis (CP). Seventy-three individuals were
      enrolled, including those with T2DM (n = 16), CP (n = 15), T2DM + CP (n = 21),
      and healthy volunteers (n = 21). PMN apoptosis was determined by flow cytometry
      using TUNEL and Annexin V assays. The activity of caspase-3, -8, and -9 was
      measured by colorimetric assay. PMN surface death receptor quantification was
      performed by flow cytometry staining with fluorescence-conjugated anti-CD120a
      (TNFR1) and anti-CD95 [Fas receptor (FasR)] antibody. Analysis of inflammatory
      markers in serum samples was performed using multiplexed sandwich immunoassays.
      In healthy volunteers and individuals with T2DM, CP, and T2DM + CP, spontaneous
      PMN apoptosis observed at 12 h reached 85.3 +/- 3.1, 67.3 +/- 3.9, 62.9 +/- 3.5
      and 62.5 +/- 5.4%, respectively (P < 0.05). Caspase-3 activity was significantly
      reduced in individuals with T2DM and T2DM + CP (P < 0.05) when compared with
      healthy volunteers. Caspase-8 activity was also significantly decreased in CP and
      T2DM + CP (P < 0.05), associated with reduced cell-surface FasR, TNFRs, and Fas
      ligand (FasL) serum levels. Glucose alone was not observed to impact PMN
      apoptosis; simultaneous incubation with the receptor for advanced glycation
      endproducts (RAGE) agonist S100B induced significant PMN apoptosis (P < 0.05).
      These data support the premise that the inhibition of PMN apoptosis in
      individuals with T2DM occurs through an advanced glycation endproducts/RAGE
      ligand/receptor-mediated interaction.

PMID- 29021371
TI  - Consumption of a Double-Fortified Salt Affects Perceptual, Attentional, and
      Mnemonic Functioning in Women in a Randomized Controlled Trial in India.
AB  - Background: Iron deficiency and iron deficiency anemia have been shown to have
      negative effects on aspects of perception, attention, and memory.Objective: The
      purpose of this investigation was to assess the extent to which increases in
      dietary iron consumption are related to improvements in behavioral measures of
      perceptual, attentional, and mnemonic function.Methods: Women were selected from
      a randomized, double-blind, controlled food-fortification trial involving ad
      libitum consumption of either a double-fortified salt (DFS) containing 47 mg
      potassium iodate/kg and 3.3 mg microencapsulated ferrous fumarate/g (1.1 mg
      elemental Fe/g) or a control iodized salt. Participants' blood iron status
      (primary outcomes) and cognitive functioning (secondary outcomes) were assessed
      at baseline and after 10 mo at endline. The study was performed on a tea
      plantation in the Darjeeling district of India. Participants (n = 126; 66% iron
      deficient and 49% anemic at baseline) were otherwise healthy women of
      reproductive age, 18-55 y.Results: Significant improvements were documented for
      iron status and for perceptual, attentional, and mnemonic function in the DFS
      group (percentage of variance accounted for: 16.5%) compared with the control
      group. In addition, the amount of change in perceptual and cognitive performance
      was significantly (P < 0.05) related to the amount of change in blood iron
      markers (mean percentage of variance accounted for: 16.0%) and baseline
      concentrations of blood iron markers (mean percentage of variance accounted for:
      25.0%). Overall, there was evidence that the strongest effects of change in iron
      status were obtained for perceptual and low-level attentional
      function.Conclusion: DFS produced measurable and significant improvements in the
      perceptual, attentional, and mnemonic performance of Indian female tea pickers of
      reproductive age. This trial was registered at clinicaltrials.gov as NCT01032005.

PMID- 29021370
TI  - Integrating Nutrition Interventions into an Existing Maternal, Neonatal, and
      Child Health Program Increased Maternal Dietary Diversity, Micronutrient Intake,
      and Exclusive Breastfeeding Practices in Bangladesh: Results of a Cluster
      Randomized Program Evaluation.
AB  - Background: Maternal undernutrition is a major concern globally, contributing to
      poor birth outcomes. Limited evidence exists on delivering multiple interventions
      for maternal nutrition simultaneously. Alive & Thrive addressed this gap by
      integrating nutrition-focused interpersonal counseling, community mobilization,
      distribution of free micronutrient supplements, and weight-gain monitoring
      through an existing Maternal, Neonatal, and Child Health (MNCH) program in
      Bangladesh.Objectives: We evaluated the effect of providing nutrition-focused
      MNCH compared with standard MNCH (antenatal care with standard nutrition
      counseling) on coverage of nutrition interventions, maternal dietary diversity,
      micronutrient supplement intake, and early breastfeeding practices.Methods: We
      used a cluster-randomized design with cross-sectional surveys at baseline (2015)
      and endline (2016) (n ~ 300 and 1000 pregnant or recently delivered women,
      respectively, per survey round). We derived difference-in-difference effect
      estimates, adjusted for geographic clustering and infant age and sex.Results:
      Coverage of interpersonal counseling was high; >90% of women in the nutrition
      focused MNCH group were visited at home by health workers for maternal nutrition
      and breastfeeding counseling. The coverage of community mobilization activities
      was ~50%. Improvements were significantly greater in the nutrition-focused MNCH
      group than in the standard MNCH group for consumption of iron and folic acid
      [effect: 9.8 percentage points (pp); 46 tablets] and calcium supplements (effect:
      12.8 pp; 50 tablets). Significant impacts were observed for the number of food
      groups consumed (effect: 1.6 food groups), percentage of women who consumed >=5
      food groups/d (effect: 30.0 pp), and daily intakes of several micronutrients. A
      significant impact was also observed for exclusive breastfeeding (EBF; effect: 31
      pp) but not for early initiation of breastfeeding.Conclusions: Addressing
      nutrition during pregnancy by delivering interpersonal counseling and community
      mobilization, providing free supplements, and ensuring weight-gain monitoring
      through an existing MNCH program improved maternal dietary diversity,
      micronutrient supplement consumption, and EBF practices. This trial was
      registered at clinicaltrials.gov as NCT02745249.

PMID- 29021372
TI  - Ammonia Nitrogen Added to Diets Deficient in Dispensable Amino Acid Nitrogen Is
      Poorly Utilized for Urea Production in Growing Pigs.
AB  - Background: Including ammonia in low-crude protein (CP) diets deficient in
      dispensable amino acid (DAAs) increases nitrogen retention in growing
      pigs.Objective: We investigated the absorption and metabolism of dietary ammonia
      nitrogen in the portal-drained viscera (PDV) and liver of pigs fed a diet
      deficient in DAA nitrogen.Methods: Eight pigs with an initial mean +/- SD body
      weight (BW) of 26.5 +/- 1.4 kg were surgically fitted with 4 catheters each
      (portal, hepatic and mesenteric veins, and carotid artery). The pigs were fed
      (2.8 * 191 kcal/kg BW0.60), for 7 d and every 8 h, a diet deficient in DAA
      nitrogen supplemented with increasing amounts of ammonia nitrogen (CP: 7.76%,
      9.27%, and 10.77%; indispensable amino acid nitrogen:total nitrogen ratio: 0.71,
      0.59, and 0.50 for control and low- and high-ammonia diets, respectively). The
      treatment sequence was based on a Latin square design with 3 consecutive periods.
      On the last day of each period, blood flows in the portal and hepatic veins were
      determined with a continuous infusion of rho-amino hippuric acid into the
      mesenteric vein. Serial blood samples were taken to determine ammonia and urea
      nitrogen concentration. Net balances of ammonia and urea nitrogen were calculated
      for the PDV and liver.Results: Cumulative (8 h) ammonia nitrogen appearance in
      the portal vein increased (P <= 0.05) with ammonia intake (433, 958, and 1629 +/-
      60 mg ammonia nitrogen/meal for control and low- and high-ammonia diets,
      respectively). The cumulative hepatic uptake of ammonia nitrogen increased (P <=
      0.05) with ammonia nitrogen supply. The cumulative urea nitrogen appearance in
      the hepatic vein tended to increase (P <= 0.10) only in high-ammonia treatment (
      92.5, -59.4, and 209.7 +/- 92 mg urea nitrogen/meal for control and low- and high
      ammonia diets, respectively) and, relative to the control diet, represented -6.0%
      and 11% of ammonia nitrogen intake.Conclusion: Dietary ammonia nitrogen is poorly
      utilized for urea production across splanchnic organs when pigs are fed diets
      deficient in DAA nitrogen.

PMID- 29021373
TI  - A Specialist Macaque MHC Class I Molecule with HLA-B*27-like Peptide-Binding
      Characteristics.
AB  - In different macaque species, the MHC A2*05 gene is present in abundance, and its
      gene products are characterized by low cell-surface expression and a highly
      conserved peptide-binding cleft. We have characterized the peptide-binding motif
      of Mamu-A2*05:01, and elucidated the binding capacity for virus-derived peptides.
      The macaque A2*05 allotype prefers the basic amino acid arginine at the second
      position of the peptide, and hydrophobic and polar amino acids at the C-terminal
      end. These preferences are shared with HLA-B*27 and Mamu-B*008, molecules shown
      to be involved in elite control in human HIV type 1 and macaque SIV infections,
      respectively. In contrast, however, Mamu-A2*05 preferentially binds 8-mer
      peptides. Retention in the endoplasmic reticulum seems to be the cause of the
      lower cell-surface expression. Subsequent peptide-binding studies have
      illustrated that Mamu-A2*05:01 is able to bind SIV-epitopes known to evoke a
      strong CD8+ T cell response in the context of the Mamu-B*008 allotype in SIV
      infected rhesus macaques. Thus, the macaque A2*05 gene encodes a specialized MHC
      class I molecule, and is most likely transported to the cell surface only when
      suitable peptides become available.

PMID- 29021374
TI  - Reactive Oxygen Species Regulate the Inflammatory Function of NKT Cells through
      Promyelocytic Leukemia Zinc Finger.
AB  - Reactive oxygen species (ROS) are byproducts of aerobic metabolism and contribute
      to both physiological and pathological conditions as second messengers. ROS are
      essential for activation of T cells, but how ROS influence NKT cells is unknown.
      In the present study, we investigated the role of ROS in NKT cell function. We
      found that NKT cells, but not CD4 or CD8 T cells, have dramatically high ROS in
      the spleen and liver of mice but not in the thymus or adipose tissues.
      Accordingly, ROS-high NKT cells exhibited increased susceptibility and apoptotic
      cell death with oxidative stress. High ROS in the peripheral NKT cells were
      primarily produced by NADPH oxidases and not mitochondria. We observed that
      sorted ROS-high NKT cells were enriched in NKT1 and NKT17 cells, whereas NKT2
      cells were dominant in ROS-low cells. Furthermore, treatment of NKT cells with
      antioxidants led to reduced frequencies of IFN-gamma- and IL-17-expressing cells,
      indicating that ROS play a role in regulating the inflammatory function of NKT
      cells. The transcription factor promyelocytic leukemia zinc finger (PLZF) seemed
      to control the ROS levels. NKT cells from adipose tissues that do not express
      PLZF and those from PLZF haplodeficient mice have low ROS. Conversely, ROS were
      highly elevated in CD4 T cells from mice ectopically expressing PLZF. Thus, our
      findings demonstrate that PLZF controls ROS levels, which in turn governs the
      inflammatory function of NKT cells.

PMID- 29021375
TI  - Maternal High Fiber Diet during Pregnancy and Lactation Influences Regulatory T
      Cell Differentiation in Offspring in Mice.
AB  - Short-chain fatty acids (SCFAs), the end products of dietary fiber, influence the
      immune system. Moreover, during pregnancy the maternal microbiome has a great
      impact on the development of the offspring's immune system. However, the exact
      mechanisms by which maternal SCFAs during pregnancy and lactation influence the
      immune system of offspring are not fully understood. We investigated the
      molecular mechanisms underlying regulatory T cell (Treg) differentiation in
      offspring regulated by a maternal high fiber diet (HFD). Plasma levels of SCFAs
      in offspring from HFD-fed mice were higher than in those from no fiber diet-fed
      mice. Consequently, the offspring from HFD-fed mice had higher frequencies of
      thymic Treg (tTreg) and peripheral Tregs We found that the offspring of HFD-fed
      mice exhibited higher autoimmune regulator (Aire) expression, a transcription
      factor expressed in the thymic microenvironment, suggesting SCFAs promote tTreg
      differentiation through increased Aire expression. Notably, the receptor for
      butyrate, G protein-coupled receptor 41 (GPR41), is highly expressed in the
      thymic microenvironment and Aire expression is not increased by stimulation with
      butyrate in GPR41-deficient mice. Our studies highlight the significance of SCFAs
      produced by a maternal HFD for Treg differentiation in the thymus of offspring.
      Given that Aire expression is associated with the induction of tTregs, the
      maternal microbiome influences Treg differentiation in the thymus of offspring
      through GPR41-mediated Aire expression.

PMID- 29021376
TI  - ARIH2 Ubiquitinates NLRP3 and Negatively Regulates NLRP3 Inflammasome Activation
      in Macrophages.
AB  - The nucleotide-binding oligomerization domain-like receptor family pyrin domain
      containing 3 (NLRP3) inflammasome is a molecular platform that induces caspase-1
      activation and subsequent IL-1beta maturation, and is implicated in inflammatory
      diseases; however, little is known about the negative regulation of NLRP3
      inflammasome activation. In this article, we identified an E3 ligase, Ariadne
      homolog 2 (ARIH2), as a posttranslational negative regulator of NLRP3
      inflammasome activity in macrophages. ARIH2 interacted with NLRP3 via its NACHT
      domain (aa 220-575) in the NLRP3 inflammasome complex. In particular, we found
      that while using mutants of ARIH2 and ubiquitin, the really interesting new gene
      2 domain of ARIH2 was required for NLRP3 ubiquitination linked through K48 and
      K63. Deletion of endogenous ARIH2 using CRISPR/Cas9 genome editing inhibited
      NLRP3 ubiquitination and promoted NLRP3 inflammasome activation, resulting in
      apoptosis-associated speck-like protein containing a caspase recruitment domain
      oligomerization, pro-IL-1beta processing, and IL-1beta production. Conversely,
      ARIH2 overexpression promoted NLRP3 ubiquitination and inhibited NLRP3
      inflammasome activation. Our findings reveal a novel mechanism of ubiquitination
      dependent negative regulation of the NLRP3 inflammasome by ARIH2 and highlight
      ARIH2 as a potential therapeutic target for inflammatory diseases.

PMID- 29021377
TI  - A Comprehensive Review of Sequencing and Combination Strategies of Targeted
      Agents in Metastatic Colorectal Cancer.
AB  - : The emergence of targeted therapies for the treatment of metastatic colorectal
      cancer (mCRC) has considerably improved survival, but has also resulted in a
      dilemma of identifying the optimal sequence and combination of various agents in
      the mCRC treatment landscape. A number of cytotoxic agents, including irinotecan,
      oxaliplatin, 5-fluorouracil, capecitabine, and TAS-102, are available for
      treatment of mCRC. Additionally, whereas patients harboring rat sarcoma viral
      oncogene homolog (RAS)-wild type mCRC can be treated with the anti-epidermal
      growth factor receptor antibodies cetuximab and panitumumab or antiangiogenic
      agents (bevacizumab, ziv-aflibercept, and ramucirumab), patients with RAS-mutant
      mCRC are limited to antiangiogenic agents as biologic options. Regorafenib, a
      multikinase inhibitor, can be used in both RAS subgroups. As such, the
      recommended sequence of therapies that should be received by each subgroup must
      also be considered separately. This review provides an overview of recent
      clinical data for approved and investigational targeted therapies that have been
      studied across different mCRC treatment lines and patient subgroups. It also
      examines emerging trends in the treatment landscape for mCRC, including treatment
      with immune checkpoint inhibitors and the utilization of genomic profiling.
      IMPLICATIONS FOR PRACTICE: Currently, there are no established guidelines for
      optimal sequencing of cytotoxic or targeted agents in metastatic colorectal
      cancer (mCRC). This review provides a snapshot of the current mCRC treatment
      paradigm and examines the latest clinical data that support the utilization of
      several targeted agents alone or in combination with backbone chemotherapy across
      different lines of treatment and patient populations, highlighting
      recommendations for their usage. Recent advances in the treatment landscape are
      also summarized, including genomic profiling and preliminary results with immune
      checkpoint inhibitors.

PMID- 29021379
TI  - Cancer Immunotherapy Trials Underutilize Immune Response Monitoring.
AB  - Immune-related radiological and biomarker monitoring in cancer immunotherapy
      trials permits interrogation of efficacy and reasons for therapeutic failure. We
      report the results from a cross-sectional analysis of response monitoring in 685
      T-cell checkpoint-targeted cancer immunotherapy trials in solid malignancies, as
      registered on the U.S. National Institutes of Health trial registry by October
      2016. Immune-related radiological response criteria were registered for only 25%
      of clinical trials. Only 38% of trials registered an exploratory immunological
      biomarker, and registration of immunological biomarkers has decreased over the
      last 15 years. We suggest that increasing the utilization of immune-related
      response monitoring across cancer immunotherapy trials will improve analysis of
      outcomes and facilitate translational efforts to extend the benefit of
      immunotherapy to a greater proportion of patients with cancer.

PMID- 29021378
TI  - Outcomes of a Specialized Interdisciplinary Approach for Patients with Cancer
      with Aberrant Opioid-Related Behavior.
AB  - BACKGROUND: Data on the development and outcomes of effective interventions to
      address aberrant opioid-related behavior (AB) in patients with cancer are
      lacking. Our outpatient supportive care clinic developed and implemented a
      specialized interdisciplinary team approach to manage patients with AB. The
      purpose of this study was to report clinical outcomes of this novel intervention.
      MATERIALS AND METHODS: The medical records of 30 consecutive patients with
      evidence of AB who received the intervention and a random control group of 70
      patients without evidence of AB between January 1, 2015, and August 31, 2016,
      were reviewed. RESULTS: At baseline, pain intensity (p = .002) and opioid dose (p
      = .001) were significantly higher among patients with AB. During the course of
      the study, the median number of ABs per month significantly decreased from three
      preintervention to 0.4 postintervention (p < .0001). The median morphine
      equivalent daily dose decreased from 165 mg/day at the first intervention visit
      to 112 mg/day at the last follow-up (p = .018), although pain intensity did not
      significantly change (p = .984). "Request for opioid medication refills in the
      clinic earlier than the expected time" was the AB with the highest frequency
      prior to the intervention and the greatest improvement during the study period.
      Younger age (p < .0001) and higher Edmonton Symptom Assessment System anxiety
      score (p = .005) were independent predictors of the presence of AB. CONCLUSION:
      The intervention was associated with a reduction in the frequency of AB and
      opioid utilization among patients with cancer receiving chronic opioid therapy.
      More research is needed to further characterize the clinical effectiveness of
      this intervention. IMPLICATIONS FOR PRACTICE: There are currently no well-defined
      and evidence-based strategies to manage cancer patients on chronic opioid therapy
      who demonstrate aberrant opioid-related behavior. The findings of this study
      offer a promising starting point for the creation of a standardized strategy for
      clinicians and provides valuable information to guide their practice regarding
      these patients. The study results will also help clinicians to better understand
      the types and frequencies of the most common aberrant behaviors observed among
      patients with cancer who are receiving chronic opioid therapy. This will enhance
      the process of timely patient identification, management, or referral to the
      appropriate specialist teams.

PMID- 29021380
TI  - Cost-Effectiveness of Nivolumab in Recurrent Metastatic Head and Neck Squamous
      Cell Carcinoma.
AB  - BACKGROUND: Treatment options for patients with platinum-refractory, recurrent,
      metastatic head and neck squamous cell carcinoma (r/m HNSCC) are limited and
      prognosis is poor. The recent CheckMate 141 clinical trial demonstrated that
      nivolumab, an anti-programmed cell death protein 1 monoclonal antibody, was
      efficacious in extending the median overall survival (OS) in this patient
      population compared with standard therapies. We conducted a cost-effectiveness
      analysis to determine whether nivolumab is a cost-effective treatment in this
      patient population and examined various subgroups to determine for which, if any,
      the treatment is more cost-effective. MATERIALS AND METHODS: We implemented a
      state transition model for HNSCC with a patient cohort who had tumor progression
      6 months after the last dose of platinum-containing chemotherapy and compared the
      cost-effectiveness of nivolumab with docetaxel. Treatment effect estimates and
      adverse event rates were obtained from CheckMate 141. Costs, utilities, and other
      model inputs were gathered from published sources. We used a Canadian
      perspective, a 5-year time horizon, and a 1.5% discount rate for the analysis.
      RESULTS: Nivolumab extended mean OS by 4 months compared with docetaxel and
      resulted in fewer treatment-related adverse events, producing an incremental
      effectiveness of 0.13 quality-adjusted life years (QALY). The incremental cost of
      treatment with nivolumab was $18,823. At a willingness-to-pay threshold of
      $100,000/QALY, nivolumab was not a cost-effective treatment option for r/m HNSCC,
      with an incremental cost-effectiveness ratio of $144,744/QALY. Nivolumab would be
      cost-effective if its price was reduced by 20%. Our subgroup analysis seemed to
      indicate that nivolumab might be cost-effective for tumors with expression of
      programmed death-ligand 1 >5%. CONCLUSION: We conclude that although nivolumab
      offers clinical benefit for the treatment of r/m HNSCC over current regimens, it
      is not cost-effective based on its list price. We have also established a value
      based price estimate for nivolumab to be cost-effective in this patient
      population. Further study is required to draw a definitive conclusion on
      biomarkers for cost-effectiveness. IMPLICATIONS FOR PRACTICE: In health care
      settings in which cost considerations are a constraint on choice of therapy,
      patient selection should be carefully considered to maintain efficiency in the
      system. Until a biomarker for response to therapy is identified for nivolumab,
      this medication is unlikely to be cost-effective for most patients with
      recurrent, metastatic head and neck squamous cell carcinoma.

PMID- 29021381
TI  - Activation of Focal Adhesion Kinase and Src Mediates Acquired Sorafenib
      Resistance in A549 Human Lung Adenocarcinoma Xenografts.
AB  - Despite encouraging clinical results with sorafenib monotherapy in patients with
      KRAS-mutant non-small-cell lung cancer (NSCLC), the overall survival benefit of
      this drug is limited by the inevitable development of acquired resistance. The
      exact mechanism underlying acquired sorafenib resistance in KRAS-mutant NSCLC is
      unclear. In this study, the mechanism of acquired sorafenib resistance was
      explored using a biologically relevant xenograft model, which was established by
      using the A549 human lung adenocarcinoma cell line and an in vivo-derived,
      sorafenib-resistant A549 subline (A549/SRFres). Results from the initial study
      demonstrated that sorafenib treatment significantly decreased E-cadherin (P <
      0.05) levels but significantly increased matrix metallopeptidase 9 (MMP9) levels
      (P < 0.01) in A549/SRFres tumors, whereas expression levels of phospho-protein
      kinase B (AKT), phospho-focal adhesion kinase (FAK), and phospho-Src were
      elevated in sorafenib-treated A549 and A549/SRFres tumors. We next examined
      whether concomitant dasatinib treatment could overcome acquired sorafenib
      resistance by blocking the FAK/Src escape route that mediates resistance. Despite
      the observed in vitro synergy between sorafenib and dasatinib, the in vivo
      antitumor effect of half-dose sorafenib-dasatinib combination therapy was
      inferior to that of the full-dose sorafenib treatment. Although the sorafenib
      dasatinib combination effectively inhibited Src and AKT phosphorylation, it did
      not block the Y576/577-FAK phosphorylation, nor did it decrease vimentin protein
      expression; unexpectedly, it increased Y397-FAK phosphorylation and MMP9 protein
      expression in tumors. These results suggest that acquired sorafenib resistance in
      KRAS-mutant A549 xenografts involves the compensatory activation of FAK and Src,
      and Src inhibition alone is insufficient to diminish sorafenib-promoted
      epithelial-mesenchymal transition process and invasive potentials in tumors.

PMID- 29021382
TI  - Sustained Activation of Guanylate Cyclase-A with TDT, a Natriuretic Peptide
      Derivative, Exhibits Cardiorenal Protection in Dahl Salt-Sensitive Hypertensive
      Rats.
AB  - Heart failure often presents with prognosis-relevant impaired renal function. To
      investigate whether the chronic activation of guanylate cyclase-A (GC-A) protects
      both heart and kidney, we examined the effects of TDT, a neprilysin (NEP)
      resistant natriuretic peptide (NP) derivative, on cardiac and renal dysfunction
      in Dahl salt-sensitive hypertensive (DS) rats. Pretreatment with NEP or NEP
      inhibitor did not influence GC-A activation by TDT both in vitro and in vivo,
      resulting in a long-acting profile of TDT compared with native human atrial NP
      (hANP). The repeated administration of TDT to DS rats suppressed the progress of
      cardiac hypertrophy, systolic/diastolic dysfunction, and proteinuria in a dose
      dependent manner. Compared with vehicle and hANP, salt diet-induced podocyte
      injury was reduced by TDT, as analyzed by urinary podocalyxin concentration,
      renal expression of nephrin mRNA, and glomerular expression of desmin protein.
      Since glomerular TRPC6 plays detrimental roles in podocyte homeostasis, we
      examined the renal expression of TRPC6 in DS rats and found that salt diet
      upregulated the expression of TRPC6. Importantly, TRPC6 induction was
      significantly decreased in TDT-treated rats, compared with vehicle and hANP.
      Consistently, in primary-culture podocytes from DS rats, TDT inhibited ATP
      induced calcium influx, similar to TRPC inhibitor SKF96365. Finally, TDT-mediated
      protection of podocytes was abolished by protein kinase G inhibitor KT5823. In
      conclusion, TDT treatment attenuated heart and kidney dysfunction, accompanied by
      podocyte protection through inhibition of TRPC6. Thus, long-acting NPs could be a
      new avenue for treatment of heart failure.

PMID- 29021383
TI  - Wnt/beta-Catenin-Promoted Macrophage Alternative Activation Contributes to Kidney
      Fibrosis.
AB  - The Wnt/beta-catenin pathway is crucial in normal development and throughout
      life, but aberrant activation of this pathway has been linked to kidney fibrosis,
      although the mechanisms involved remain incompletely determined. Here, we
      investigated the role of Wnt/beta-catenin in regulating macrophage activation and
      the contribution thereof to kidney fibrosis. Treatment of macrophages with Wnt3a
      exacerbated IL-4- or TGFbeta1-induced macrophage alternative (M2) polarization
      and the phosphorylation and nuclear translocation of STAT3 in vitro Conversely,
      inhibition of Wnt/beta-catenin signaling prevented these IL-4- or TGFbeta1
      induced processes. In a mouse model, induced deletion of beta-catenin in
      macrophages attenuated the fibrosis, macrophage accumulation, and M2 polarization
      observed in the kidneys of wild-type littermates after unilateral ureter
      obstruction. This study shows that activation of Wnt/beta-catenin signaling
      promotes kidney fibrosis by stimulating macrophage M2 polarization.

PMID- 29021387
TI  - Timing of onset of symptoms in people with idiopathic pulmonary fibrosis.
AB  - Little is known about when symptoms of idiopathic pulmonary fibrosis first
      develop. We identified incident cases of idiopathic pulmonary fibrosis-clinical
      syndrome (IPF-CS) from a UK primary care database and assessed the frequency of
      consultations for common symptoms in the 5 years prior to diagnosis. 1671 cases
      were identified with 5 years of data prior to diagnosis. Breathlessness was the
      most common symptom, followed by cough. Cases were significantly more likely than
      controls to experience these symptoms (p<0.001), even 4-5 years before diagnosis
      (OR for breathlessness for this period 2.79, 95% CI 2.13 to 3.65). This suggests
      that some patients with IPF may be symptomatic for more than 5 years before
      diagnosis.

PMID- 29021384
TI  - Impaired beta-Oxidation and Altered Complex Lipid Fatty Acid Partitioning with
      Advancing CKD.
AB  - Studies of lipids in CKD, including ESRD, have been limited to measures of
      conventional lipid profiles. We aimed to systematically identify 17 different
      lipid classes and associate the abundance thereof with alterations in
      acylcarnitines, a metric of beta-oxidation, across stages of CKD. From the
      Clinical Phenotyping Resource and Biobank Core (CPROBE) cohort of 1235 adults, we
      selected a panel of 214 participants: 36 with stage 1 or 2 CKD, 99 with stage 3
      CKD, 61 with stage 4 CKD, and 18 with stage 5 CKD. Among participants, 110 were
      men (51.4%), 64 were black (29.9%), and 150 were white (70.1%), and the mean (SD)
      age was 60 (16) years old. We measured plasma lipids and acylcarnitines using
      liquid chromatography-mass spectrometry. Overall, we identified 330 different
      lipids across 17 different classes. Compared with earlier stages, stage 5 CKD
      associated with a higher abundance of saturated C16-C20 free fatty acids (FFAs)
      and long polyunsaturated complex lipids. Long-chain-to-intermediate-chain
      acylcarnitine ratio, a marker of efficiency of beta-oxidation, exhibited a graded
      decrease from stage 2 to 5 CKD (P<0.001). Additionally, multiple linear
      regression revealed that the long-chain-to-intermediate-chain acylcarnitine ratio
      inversely associated with polyunsaturated long complex lipid subclasses and the
      C16-C20 FFAs but directly associated with short complex lipids with fewer double
      bonds. We conclude that increased abundance of saturated C16-C20 FFAs coupled
      with impaired beta-oxidation of FFAs and inverse partitioning into complex lipids
      may be mechanisms underpinning lipid metabolism changes that typify advancing
      CKD.

PMID- 29021388
TI  - In vivo beta and gamma subthreshold oscillations in rat mitral cells: origin and
      gating by respiratory dynamics.
AB  - In mammals, olfactory bulb (OB) dynamics are paced by slow and fast oscillatory
      rhythms at multiple levels: local field potential, spike discharge, and/or
      membrane potential oscillations. Interactions between these levels have been well
      studied for the slow rhythm linked to animal respiration. However, less is known
      regarding rhythms in the fast beta (10-35 Hz) and gamma (35-100 Hz) frequency
      ranges, particularly at the membrane potential level. Using a combination of
      intracellular and extracellular recordings in the OB of freely breathing rats, we
      show that beta and gamma subthreshold oscillations (STOs) coexist intracellularly
      and are related to extracellular local field potential (LFP) oscillations in the
      same frequency range. However, they are differentially affected by changes in
      cell excitability and by odor stimulation. This leads us to suggest that beta and
      gamma STOs may rely on distinct mechanisms: gamma STOs would mainly depend on
      mitral cell intrinsic resonance, while beta STOs could be mainly driven by
      synaptic activity. In a second study, we find that STO occurrence and timing are
      constrained by the influence of the slow respiratory rhythm on mitral and tufted
      cells. First, respiratory-driven excitation seems to favor gamma STOs, while
      respiratory-driven inhibition favors beta STOs. Second, the respiratory rhythm is
      needed at the subthreshold level to lock gamma and beta STOs in similar phases as
      their LFP counterparts and to favor the correlation between STO frequency and
      spike discharge. Overall, this study helps us to understand how the interaction
      between slow and fast rhythms at all levels of OB dynamics shapes its functional
      output. NEW & NOTEWORTHY In the mammalian olfactory bulb of a freely breathing
      anesthetized rat, we show that both beta and gamma membrane potential fast
      oscillation ranges exist in the same mitral and tufted (M/T) cell. Importantly,
      our results suggest they have different origins and that their interaction with
      the slow subthreshold oscillation (respiratory rhythm) is a key mechanism to
      organize their dynamics, favoring their functional implication in olfactory bulb
      information processing.

PMID- 29021386
TI  - Suppression of microRNA Activity in Kidney Collecting Ducts Induces Partial Loss
      of Epithelial Phenotype and Renal Fibrosis.
AB  - microRNAs (miRNAs) are sequence-specific inhibitors of post-transcriptional gene
      expression. The physiologic function of these noncoding RNAs in postnatal renal
      tubules still remains unclear. Surprisingly, they appear to be dispensable for
      mammalian proximal tubule (PT) function. Here, we examined the effects of miRNA
      suppression in collecting ducts (CDs). To conclusively evaluate the role of
      miRNAs, we generated three mouse models with CD-specific inactivation of key
      miRNA pathway genes Dicer, Dgcr8, and the entire Argonaute gene family (Ago1, 2,
      3, and 4). Characterization of these three mouse models revealed that inhibition
      of miRNAs in CDs spontaneously evokes a renal tubule injury-like response, which
      culminates in progressive tubulointerstitial fibrosis (TIF) and renal failure.
      Global miRNA profiling of microdissected renal tubules showed that miRNAs exhibit
      segmental distribution along the nephron and CDs. In particular, the expression
      of miR-200c is nearly 70-fold higher in CDs compared with PTs. Accordingly, miR
      200s are downregulated in Dicer-KO CDs, its direct target genes Zeb1, Zeb2, and
      Snail2 are upregulated, and miRNA-depleted CDs undergo partial epithelial-to
      mesenchymal transition (EMT). Thus, miRNAs are essential for CD homeostasis.
      Downregulation of CD-enriched miRNAs and the subsequent induction of partial EMT
      may be a new mechanism for TIF progression.

PMID- 29021385
TI  - Aldosterone Is Essential for Angiotensin II-Induced Upregulation of Pendrin.
AB  - The renin-angiotensin-aldosterone system has an important role in the control of
      fluid homeostasis and BP during volume depletion. Dietary salt restriction
      elevates circulating angiotensin II (AngII) and aldosterone levels, increasing
      levels of the Cl-/HCO3- exchanger pendrin in beta-intercalated cells and the Na+
      Cl- cotransporter (NCC) in distal convoluted tubules. However, the independent
      roles of AngII and aldosterone in regulating these levels remain unclear. In
      C57BL/6J mice receiving a low-salt diet or AngII infusion, we evaluated the
      membrane protein abundance of pendrin and NCC; assessed the phosphorylation of
      the mineralocorticoid receptor, which selectively inhibits aldosterone binding in
      intercalated cells; and measured BP by radiotelemetry in pendrin-knockout and
      wild-type mice. A low-salt diet or AngII infusion upregulated NCC and pendrin
      levels, decreased the phosphorylation of mineralocorticoid receptor in beta
      intercalated cells, and increased plasma aldosterone levels. Notably, a low-salt
      diet did not alter BP in wild-type mice, but significantly decreased BP in
      pendrin-knockout mice. To dissect the roles of AngII and aldosterone, we
      performed adrenalectomies in mice to remove aldosterone from the circulation. In
      adrenalectomized mice, AngII infusion again upregulated NCC expression, but did
      not affect pendrin expression despite the decreased phosphorylation of
      mineralocorticoid receptor. By contrast, AngII and aldosterone coadministration
      markedly elevated pendrin levels in adrenalectomized mice. Our results indicate
      that aldosterone is necessary for AngII-induced pendrin upregulation, and suggest
      that pendrin contributes to the maintenance of normal BP in cooperation with NCC
      during activation of the renin-angiotensin-aldosterone system by dietary salt
      restriction.

PMID- 29021390
TI  - Eye-hand coordination during flexible manual interception of an abruptly
      appearing, moving target.
AB  - As a vital skill in an evolving world, interception of moving objects relies on
      accurate prediction of target motion. In natural circumstances, active gaze
      shifts often accompany hand movements when exploring targets of interest, but how
      eye and hand movements are coordinated during manual interception and their
      dependence on visual prediction remain unclear. Here, we trained gaze
      unrestrained monkeys to manually intercept targets appearing at random locations
      and circularly moving with random speeds. We found that well-trained animals were
      able to intercept the targets with adequate compensation for both sensory
      transmission and motor delays. Before interception, the animals' gaze followed
      the targets with adequate compensation for the sensory delay, but not for extra
      target displacement during the eye movements. Both hand and eye movements were
      modulated by target kinematics, and their reaction times were correlated.
      Moreover, retinal errors and reaching errors were correlated across different
      stages of reach execution. Our results reveal eye-hand coordination during manual
      interception, yet the eye and hand movements may show different levels of
      prediction based on the task context. NEW & NOTEWORTHY Here we studied the eye
      hand coordination of monkeys during flexible manual interception of a moving
      target. Eye movements were untrained and not explicitly associated with reward.
      We found that the initial saccades toward the moving target adequately
      compensated for sensory transmission delays, but not for extra target
      displacement, whereas the reaching arm movements fully compensated for
      sensorimotor delays, suggesting that the mode of eye-hand coordination strongly
      depends on behavioral context.

PMID- 29021389
TI  - Norepinephrine enhances song responsiveness and encoding in the auditory
      forebrain of male zebra finches.
AB  - Norepinephrine (NE) can dynamically modulate excitability and functional
      connectivity of neural circuits in response to changes in external and internal
      states. Regulation by NE has been demonstrated extensively in mammalian sensory
      cortices, but whether NE-dependent modulation in sensory cortex alters response
      properties in downstream sensorimotor regions is less clear. Here we examine this
      question in male zebra finches, a songbird species with complex vocalizations and
      a well-defined neural network for auditory processing of those vocalizations. We
      test the hypothesis that NE modulates auditory processing and encoding, using
      paired extracellular electrophysiology recordings and pattern classifier
      analyses. We report that a NE infusion into the auditory cortical region NCM
      (caudomedial nidopallium; analogous to mammalian secondary auditory cortex)
      enhances the auditory responses, burst firing, and coding properties of single
      NCM neurons. Furthermore, we report that NE-dependent changes in NCM coding
      properties, but not auditory response strength, are transmitted downstream to the
      sensorimotor nucleus HVC. Finally, NE modulation in the NCM of males is
      qualitatively similar to that observed in females: in both sexes, NE increases
      auditory response strengths. However, we observed a sex difference in the
      mechanism of enhancement: whereas NE increases response strength in females by
      decreasing baseline firing rates, NE increases response strength in males by
      increasing auditory-evoked activity. Therefore, NE signaling exhibits a
      compensatory sex difference to achieve a similar, state-dependent enhancement in
      signal-to-noise ratio and coding accuracy in males and females. In summary, our
      results provide further evidence for adrenergic regulation of sensory processing
      and modulation of auditory/sensorimotor functional connectivity. NEW & NOTEWORTHY
      This study documents that the catecholamine norepinephrine (also known as
      noradrenaline) acts in the auditory cortex to shape local processing of complex
      sound stimuli. Moreover, it also enhances the coding accuracy of neurons in the
      auditory cortex as well as in the downstream sensorimotor cortex. Finally, this
      study shows that while the sensory-enhancing effects of norepinephrine are
      similar in males and females, there are sex differences in the mode of action.

PMID- 29021392
TI  - Saccades and reaches curve away from the other effector's target in simultaneous
      eye and hand movements.
AB  - Simultaneous eye and hand movements are highly coordinated and tightly coupled.
      This raises the question whether the selection of eye and hand targets relies on
      a shared attentional mechanism or separate attentional systems. Previous studies
      have revealed conflicting results by reporting evidence for both a shared as well
      as separate systems. Movement properties such as movement curvature can provide
      novel insights into this question as they provide a sensitive measure for
      attentional allocation during target selection. In the current study,
      participants performed simultaneous eye and hand movements to the same or
      different visual target locations. We show that both saccade and reaching
      movements curve away from the other effector's target location when they are
      simultaneously performed to spatially distinct locations. We argue that there is
      a shared attentional mechanism involved in selecting eye and hand targets that
      may be found on the level of effector-independent priority maps. NEW & NOTEWORTHY
      Movement properties such as movement curvature have been widely neglected as
      important sources of information in investigating whether the attentional systems
      underlying target selection for eye and hand movements are separate or shared. We
      convincingly show that movement curvature is influenced by the other effector's
      target location in simultaneous eye and hand movements to spatially distinct
      locations. Our results provide evidence for shared attentional systems involved
      in the selection of saccade and reach targets.

PMID- 29021393
TI  - Phrenic motoneurons: output elements of a highly organized intraspinal network.
AB  - pontomedullary respiratory network generates the respiratory pattern and relays
      it to bulbar and spinal respiratory motor outputs. The phrenic motor system
      controlling diaphragm contraction receives and processes descending commands to
      produce orderly, synchronous, and cycle-to-cycle-reproducible spatiotemporal
      firing. Multiple investigators have studied phrenic motoneurons (PhMNs) in an
      attempt to shed light on local mechanisms underlying phrenic pattern formation. I
      and colleagues (Marchenko V, Ghali MG, Rogers RF. Am J Physiol Regul Integr Comp
      Physiol 308: R916-R926, 2015.) recorded PhMNs in unanesthetized, decerebrate rats
      and related their activity to simultaneous phrenic nerve (PhN) activity by
      creating a time-frequency representation of PhMN-PhN power and coherence. On the
      basis of their temporal firing patterns and relationship to PhN activity, we
      categorized PhMNs into three classes, each of which emerges as a result of
      intrinsic biophysical and network properties and organizes the orderly
      contraction of diaphragm motor fibers. For example, early inspiratory
      diaphragmatic activation by the early coherent burst generated by high-frequency
      PhMNs may be necessary to prime it to overcome its initial inertia. We have also
      demonstrated the existence of a prominent role for local intraspinal inhibitory
      mechanisms in shaping phrenic pattern formation. The objective of this review is
      to relate and synthesize recent findings with those of previous studies with the
      aim of demonstrating that the phrenic nucleus is a region of active local
      processing, rather than a passive relay of descending inputs.

PMID- 29021391
TI  - A dual-axis rotation rule for updating the head direction cell reference frame
      during movement in three dimensions.
AB  - In the mammalian brain, allocentric (Earth-referenced) head direction, called
      azimuth, is encoded by head direction (HD) cells, which fire according to the
      facing direction of the animal's head. On a horizontal surface, rotations of the
      head around the dorsoventral (D-V) axis, called yaw, correspond to changes in
      azimuth and elicit appropriate updating of the HD "compass" signal to enable
      large-scale navigation. However, if the animal moves through three-dimensional
      (3D) space then there is no longer a simple relationship between yaw rotations
      and azimuth changes, and so processing of 3D rotations is needed. Construction of
      a global 3D compass would require complex integration of 3D rotations, and also a
      large neuronal population, most neurons of which would be silent most of the time
      since animals rarely sample all available 3D orientations. We propose that,
      instead, the HD system treats the 3D space as a set of interrelated 2D surfaces.
      It could do this by updating activity according to both yaw rotations around the
      D-V axis and rotations of the D-V axis around the gravity-defined vertical axis.
      We present preliminary data to suggest that this rule operates when rats move
      between walls of opposing orientations. This dual-axis rule, which we show is
      straightforward to implement using the classic one-dimensional "attractor"
      architecture, allows consistent representation of azimuth even in volumetric
      space and thus may be a general feature of mammalian directional computations
      even for animals that swim or fly. NEW & NOTEWORTHY Maintaining a sense of
      direction is complicated when moving in three-dimensional (3D) space. Head
      direction cells, which update the direction sense based on head rotations, may
      accommodate 3D movement by processing both rotations of the head around the axis
      of the animal's body and rotations of the head/body around gravity. With modeling
      we show that this dual-axis rule works in principle, and we present preliminary
      data to support its operation in rats.

PMID- 29021394
TI  - HIV-1 gp120 and Modified Vaccinia Virus Ankara (MVA) gp140 Boost Immunogens
      Increase Immunogenicity of a DNA/MVA HIV-1 Vaccine.
AB  - An important goal of human immunodeficiency virus (HIV) vaccine design is
      identification of strategies that elicit effective antiviral humoral immunity.
      One novel approach comprises priming with DNA and boosting with modified vaccinia
      virus Ankara (MVA) expressing HIV-1 Env on virus-like particles. In this study,
      we evaluated whether the addition of a gp120 protein in alum or MVA-expressed
      secreted gp140 (MVAgp140) could improve immunogenicity of a DNA prime-MVA boost
      vaccine. Five rhesus macaques per group received two DNA primes at weeks 0 and 8
      followed by three MVA boosts (with or without additional protein or MVAgp140) at
      weeks 18, 26, and 40. Both boost immunogens enhanced the breadth of HIV-1 gp120
      and V1V2 responses, antibody-dependent cellular cytotoxicity (ADCC), and low
      titer tier 1B and tier 2 neutralizing antibody responses. However, there were
      differences in antibody kinetics, linear epitope specificity, and CD4 T cell
      responses between the groups. The gp120 protein boost elicited earlier and higher
      peak responses, whereas the MVAgp140 boost resulted in improved antibody
      durability and comparable peak responses after the final immunization. Linear V3
      specific IgG responses were particularly enhanced by the gp120 boost, whereas the
      MVAgp140 boost also enhanced responses to linear C5 and C2.2 epitopes.
      Interestingly, gp120, but not the MVAgp140 boost, increased peak CD4+ T cell
      responses. Thus, both gp120 and MVAgp140 can augment potential protection of a
      DNA/MVA vaccine by enhancing gp120 and V1/V2 antibody responses, whereas
      potential protection by gp120, but not MVAgp140 boosts, may be further impacted
      by increased CD4+ T cell responses.IMPORTANCE Prior immune correlate analyses
      with humans and nonhuman primates revealed the importance of antibody responses
      in preventing HIV-1 infection. A DNA prime-modified vaccinia virus Ankara (MVA)
      boost vaccine has proven to be potent in eliciting antibody responses. Here we
      explore the ability of boosts with recombinant gp120 protein or MVA-expressed
      gp140 to enhance antibody responses elicited by the GOVX-B11 DNA prime-MVA boost
      vaccine. We found that both types of immunogen boosts enhanced potentially
      protective antibody responses, whereas the gp120 protein boosts also increased
      CD4+ T cell responses. Our data provide important information for HIV vaccine
      designs that aim for effective and balanced humoral and T cell responses.

PMID- 29021395
TI  - HCMV utilizes a non-traditional STAT1 activation cascade via signaling through
      EGFR and integrins to efficiently promote the motility, differentiation, and
      polarization of infected monocytes.
AB  - Human cytomegalovirus infects peripheral blood monocytes and triggers biological
      changes that promote viral dissemination and persistence. We have shown that HCMV
      induces a pro-inflammatory state in infected monocytes, resulting in enhanced
      monocyte motility and transendothelial migration, prolonged monocyte survival,
      and differentiation toward a long-lived M1-like macrophage phenotype. Our data
      indicate that HCMV triggers these changes, in the absence of de novo viral gene
      expression and replication, through engagement and activation of EGFR and
      integrins on the surface of monocytes. We previously identified that HCMV induces
      the upregulation of multiple pro-inflammatory gene ontologies, with the
      interferon-associated gene ontology exhibiting the highest percentage of
      upregulated genes. However, the function of the HCMV-induced ISGs in infected
      monocytes remained unclear. We now show that HCMV induces the enhanced expression
      and activation of a key ISG transcriptional regulator, STAT1, via an IFN
      independent, but EGFR- and integrin-dependent signaling pathway. Furthermore, we
      identified a biphasic activation of STAT1 that likely promotes two distinct
      phases of STAT1-mediated transcriptional activity. Moreover, our data show that
      STAT1 is required for efficient early HCMV-induced enhanced monocyte motility and
      later for HCMV-induced monocyte-to-macrophage differentiation and for the
      regulation of macrophage polarization, suggesting that STAT1 may serve as a
      molecular convergence point linking the biological changes that occur at early
      and later times post infection. Taken together, our results suggest that HCMV re
      routes the biphasic activation of a traditionally anti-viral gene product through
      an EGFR- and integrin-dependent pathway in order to help promote the pro-viral
      activation and polarization of infected monocytes.IMPORTANCE HCMV promotes
      multiple functional changes in infected monocytes that are required for viral
      spread and persistence, including their enhanced motility and
      differentiation/polarization towards a pro-inflammatory M1 macrophage. We now
      show that HCMV utilizes the traditionally IFN-associated gene product, STAT1, to
      promote these changes. Our data suggest that HCMV utilizes EGFR- and integrin
      dependent (but IFN-independent) signaling pathways to induce STAT1 activation,
      which may allow the virus to specifically dictate the biological activity of
      STAT1 during infection. Our data indicate that HCMV utilizes two phases of STAT1
      activation, which we argue molecularly links the biological changes that occur
      following initial binding to those that continue to occur days to weeks following
      infection. Furthermore, our findings may highlight a unique mechanism for how
      HCMV avoids the anti-viral response during infection by hijacking the function of
      a critical component of the IFN response pathway.

PMID- 29021396
TI  - Quiescence Promotes Latent HIV Infection and Resistance to Reactivation from
      Latency with Histone Deacetylase Inhibitors.
AB  - Human immunodeficiency virus type 1 (HIV-1) establishes transcriptionally silent
      latent infections in resting memory T cells and hematopoietic stem and progenitor
      cells (HSPCs), which allows the virus to persist in infected individuals despite
      antiretroviral therapy. Developing in vitro models of HIV-1 latency that
      recapitulate the characteristics of latently infected cells in vivo is crucial to
      identifying and developing effective latency-reversing therapies. HSPCs exist in
      a quiescent state in vivo, and quiescence is correlated with latent infections in
      T cells. However, current models for culturing HSPCs and for infecting T cells in
      vitro require that the cells be maintained in an actively proliferating state.
      Here we describe a novel culture system in which primary human HSPCs cultured
      under hypothermic conditions are maintained in a quiescent state. We show that
      these quiescent HSPCs are susceptible to predominantly latent infection with HIV
      1, while actively proliferating and differentiating HSPCs obtain predominantly
      active infections. Furthermore, we demonstrate that the most primitive quiescent
      HSPCs are more resistant to spontaneous reactivation from latency than more
      differentiated HSPCs and that quiescent HSPCs are resistant to reactivation by
      histone deacetylase inhibitors or P-TEFb activation but are susceptible to
      reactivation by protein kinase C (PKC) agonists. We also demonstrate that
      inhibition of HSP90, a known regulator of HIV transcription, recapitulates the
      quiescence and latency phenotypes of hypothermia, suggesting that hypothermia and
      HSP90 inhibition may regulate these processes by similar mechanisms. In summary,
      these studies describe a novel model for studying HIV-1 latency in human primary
      cells maintained in a quiescent state.IMPORTANCE Human immunodeficiency virus
      type 1 (HIV-1) establishes a persistent infection for which there remains no
      feasible cure. Current approaches are unable to clear the virus despite decades
      of therapy due to the existence of latent reservoirs of integrated HIV-1, which
      can reactivate and contribute to viral rebound following treatment interruption.
      Previous clinical attempts to reactivate the latent reservoirs in an individual
      so that they can be eliminated by the immune response or viral cytopathic effect
      have failed, indicating the need for a better understanding of the processes
      regulating HIV-1 latency. Here we characterize a novel in vitro model of HIV-1
      latency in primary hematopoietic stem and progenitor cells isolated from human
      cord blood that may better recapitulate the behavior of latently infected cells
      in vivo This model can be used to study mechanisms regulating latency and
      potential therapeutic approaches to reactivate latent infections in quiescent
      cells.

PMID- 29021397
TI  - Varicella-Zoster Virus Expresses Multiple Small Noncoding RNAs.
AB  - Many herpesviruses express small noncoding RNAs (sncRNAs), including microRNAs
      (miRNAs), that may play roles in regulating lytic and latent infections. None
      have yet been reported in varicella-zoster virus (VZV; also known as human
      herpesvirus 3 [HHV-3]). Here we analyzed next-generation sequencing (NGS) data
      for small RNAs in VZV-infected fibroblasts and human embryonic stem cell-derived
      (hESC) neurons. Two independent bioinformatics analyses identified more than 20
      VZV-encoded 20- to 24-nucleotide RNAs, some of which are predicted to have stem
      loop precursors potentially representing miRNAs. These sequences are perfectly
      conserved between viruses from three clades of VZV. One NGS-identified sequence
      common to both bioinformatics analyses mapped to the repeat regions of the VZV
      genome, upstream of the predicted promoter of the immediate early gene open
      reading frame 63 (ORF63). This miRNA candidate was detected in each of 3
      independent biological repetitions of NGS of RNA from fibroblasts and neurons
      productively infected with VZV using TaqMan quantitative PCR (qPCR). Importantly,
      transfected synthetic RNA oligonucleotides antagonistic to the miRNA candidate
      significantly enhanced VZV plaque growth rates. The presence of 6 additional
      small noncoding RNAs was also verified by TaqMan qPCR in productively infected
      fibroblasts and ARPE19 cells. Our results show VZV, like other human
      herpesviruses, encodes several sncRNAs and miRNAs, and some may regulate
      infection of host cells.IMPORTANCE Varicella-zoster virus is an important human
      pathogen, with herpes zoster being a major health issue in the aging and
      immunocompromised populations. Small noncoding RNAs (sncRNAs) are recognized as
      important actors in modulating gene expression, and this study demonstrates the
      first reported VZV-encoded sncRNAs. Many are clustered to a small genomic region,
      as seen in other human herpesviruses. At least one VZV sncRNA was expressed in
      productive infection of neurons and fibroblasts that is likely to reduce viral
      replication. Since sncRNAs have been suggested to be potential targets for
      antiviral therapies, identification of these molecules in VZV may provide a new
      direction for development of treatments for painful herpes zoster.

PMID- 29021398
TI  - Characterization of the African Swine Fever Virus Decapping Enzyme during
      Infection.
AB  - African swine fever virus (ASFV) infection is characterized by a progressive
      decrease in cellular protein synthesis with a concomitant increase in viral
      protein synthesis, though the mechanism by which the virus achieves this is still
      unknown. Decrease of cellular mRNA is observed during ASFV infection, suggesting
      that inhibition of cellular proteins is due to an active mRNA degradation
      process. ASFV carries a gene (Ba71V D250R/Malawi g5R) that encodes a decapping
      protein (ASFV-DP) that has a Nudix hydrolase motif and decapping activity in
      vitro Here, we show that ASFV-DP was expressed from early times and accumulated
      throughout the infection with a subcellular localization typical of the
      endoplasmic reticulum, colocalizing with the cap structure and interacting with
      the ribosomal protein L23a. ASFV-DP was capable of interaction with poly(A) RNA
      in cultured cells, primarily mediated by the N-terminal region of the protein.
      ASFV-DP also interacted with viral and cellular RNAs in the context of infection,
      and its overexpression in infected cells resulted in decreased levels of both
      types of transcripts. This study points to ASFV-DP as a viral decapping enzyme
      involved in both the degradation of cellular mRNA and the regulation of viral
      transcripts.IMPORTANCE Virulent ASFV strains cause a highly infectious and lethal
      disease in domestic pigs for which there is no vaccine. Since 2007, an outbreak
      in the Caucasus region has spread to Russia, jeopardizing the European pig
      population and making it essential to deepen knowledge about the virus. Here, we
      demonstrate that ASFV-DP is a novel RNA-binding protein implicated in the
      regulation of mRNA metabolism during infection, making it a good target for
      vaccine development.

PMID- 29021399
TI  - Modeling of Antilatency Treatment in HIV: What Is the Optimal Duration of
      Antiretroviral Therapy-Free HIV Remission?
AB  - A number of treatment strategies are currently being developed to promote
      antiretroviral therapy-free HIV cure or remission. While complete elimination of
      the HIV reservoir would prevent recurrence of infection, it is not clear how
      different remission lengths would affect viral rebound and transmission. In this
      work, we use a stochastic model to show that a treatment that achieves a 1-year
      average time to viral remission will still lead to nearly a quarter of subjects
      experiencing viral rebound within the first 3 months. Given quarterly viral
      testing intervals, this leads to an expected 39 (95% uncertainty interval [UI],
      22 to 69) heterosexual transmissions and up to 262 (95% UI, 107 to 534)
      homosexual transmissions per 1,000 treated subjects over a 10-year period. Thus,
      a balance between high initial treatment levels, risk of recrudescence, and risk
      of transmission should be considered when assessing the "useful" or optimal
      length of antiretroviral therapy-free HIV remission to be targeted. We also
      investigate the trade-off between increasing the average duration of remission
      versus the risk of treatment failure (viral recrudescence) and the need for
      retreatment. To minimize drug exposure, we found that the optimal target of
      antilatency interventions is a 1,700-fold reduction in the size of the reservoir,
      which leads to an average time to recrudescence of 30 years. Interestingly, this
      is a significantly lower level of reduction than that required for complete
      elimination of the viral reservoir. Additionally, we show that when shorter
      periods are targeted, there is a real probability of viral transmission occurring
      between tests for viral rebound.IMPORTANCE Current treatment of HIV involves
      patients taking antiretroviral therapy to ensure that the level of virus remains
      very low or undetectable. Continuous therapy is required, as the virus persists
      in a latent state within cells, and when therapy is stopped, the virus rebounds,
      usually within 2 weeks. A major question is how to reduce the amount of
      persistent virus and therefore allow a delay or remission until the virus returns
      after ceasing therapy. In this work, we consider the probability that HIV will
      still rebound even after this reduction and ask what the likelihood of viral
      transmission would be in this case.

PMID- 29021401
TI  - RNASeq analysis of differentiated keratinocytes reveals a massive response to
      late events during human papillomavirus type 16 infection, including loss of
      epithelial barrier function.
AB  - The human papillomavirus (HPV) replication cycle is tightly linked to epithelial
      cell differentiation. To examine HPV-associated changes in the keratinocyte
      transcriptome, RNAs isolated from undifferentiated and differentiated cell
      populations of normal, spontaneously immortalised, keratinocytes (NIKS), and NIKS
      stably transfected with HPV16 episomal genomes (NIKS16), were compared using
      RNASeq. HPV16 infection altered expression of 2862 cellular genes. Next, to
      elucidate the role of keratinocyte gene expression in late events during the
      viral life cycle, RNASeq was carried out on triplicate differentiated populations
      of NIKS (uninfected) and NIKS16 (infected). Of the top 966 genes altered (>log2 =
      1.8, 3.5-fold change) 670 genes were downregulated and 296 genes were up
      regulated. HPV down-regulated many genes involved in epithelial barrier function
      that involves structural resistance to the environment and immunity to infectious
      agents. For example, HPV infection repressed expression of the differentiated
      keratinocyte-specific pattern recognition receptor TLR7, the Langerhans cell
      chemoattractant, CCL20, and proinflammatory cytokines, IL1A and IL1B. However,
      IRF1, IFNkappa and viral restriction factors (IFIT1, 2, 3, 5, OASL, CD74, RTP4)
      were up-regulated. HPV infection abrogated gene expression associated with the
      physical epithelial barrier, including keratinocyte cytoskeleton, intercellular
      junctions and cell adhesion. qPCR and western blotting confirmed changes in
      expression of seven of the most significantly altered mRNAs. Expression of three
      genes showed statistically significant changes during cervical disease
      progression in clinical samples. Taken together, the data indicate that HPV
      infection manipulates the differentiating keratinocyte transcriptome to create an
      environment conducive to productive viral replication and egress.IMPORTANCE Human
      papillomavirus (HPV) genome amplification and capsid formation takes place in
      differentiated keratinocytes. The viral life cycle is intimately associated with
      host cell differentiation. Deep sequencing (RNASeq) of RNA from undifferentiated
      and differentiated uninfected and HPV16-positive keratinocytes showed that almost
      3000 genes were differentially expressed in keratinocyte due to HPV16 infection.
      Strikingly, the epithelial barrier function of differentiated keratinocytes,
      comprising keratinocyte immune function and cellular structure, was found to be
      disrupted. These data provide new insights into virus-host interaction crucial
      for production of infectious virus and reveal that HPV infection remodels
      keratinocytes for completion of the virus replication cycle.

PMID- 29021404
TI  - Sex differences in the significance of isolated reactive treponemal
      chemiluminescence immunoassay results.
AB  - OBJECTIVES: The significance of sera with isolated reactive treponemal
      chemiluminescence immunoassay (IRTCIA) results is unclear. Women have this
      phenotype more commonly than men. Most cohorts examining this phenotype have
      included predominantly men and have demonstrated evidence of past or subsequently
      confirmed syphilis infection in a significant proportion of cases. We
      hypothesised that a proportion of sera with IRTCIA results would be positive on
      immunoblot testing and that sera from women with IRTCIA would have different
      results in immunoblot testing than men. METHODS: IRTCIA sera from a tertiary
      referral serology laboratory serving multiple clinical sites were analysed with a
      syphilis line immunoblot assay (LIA) and analysed by sex. Logistic regression was
      undertaken to assess factors associated with LIA status. Medical record review
      and descriptive analysis of a separate cohort of women with the IRTCIA phenotype
      from a single campus was also undertaken. RESULTS: Overall, 19/63 (30.1%)
      subjects with the IRTCIA phenotype were positive in the LIA, including 13 men and
      6 women. Women were significantly less likely to have definitive results
      (positive or negative) than men (p=0.015). Pregnant women were less likely than
      non-pregnant women to have a negative LIA result (OR 0.57; p=0.03). Record review
      of 22 different women with IRTCIA reactivity showed that 2/22 (9.1%) had HIV and
      previous syphilis infection, 15/22 (68.2%) were pregnant and 3 (13.6%) had
      autoimmune disease. CONCLUSIONS: A significant proportion of sera with IRTCIA
      results on serological tests are reactive on LIA testing and some may not be
      false positive results. The interpretation of IRTCIA results should be undertaken
      in conjunction with an assessment of factors such as sex, pregnancy, a history of
      syphilis and other STIs and syphilis risk.

PMID- 29021403
TI  - Heterozygous mutations affecting the protein kinase domain of CDK13 cause a
      syndromic form of developmental delay and intellectual disability.
AB  - INTRODUCTION: Recent evidence has emerged linking mutations in CDK13 to syndromic
      congenital heart disease. We present here genetic and phenotypic data pertaining
      to 16 individuals with CDK13 mutations. METHODS: Patients were investigated by
      exome sequencing, having presented with developmental delay and additional
      features suggestive of a syndromic cause. RESULTS: Our cohort comprised 16
      individuals aged 4-16 years. All had developmental delay, including six with
      autism spectrum disorder. Common findings included feeding difficulties (15/16),
      structural cardiac anomalies (9/16), seizures (4/16) and abnormalities of the
      corpus callosum (4/11 patients who had undergone MRI). All had craniofacial
      dysmorphism, with common features including short, upslanting palpebral fissures,
      hypertelorism or telecanthus, medial epicanthic folds, low-set, posteriorly
      rotated ears and a small mouth with thin upper lip vermilion. Fifteen patients
      had predicted missense mutations, including five identical p.(Asn842Ser)
      substitutions and two p.(Gly717Arg) substitutions. One patient had a canonical
      splice acceptor site variant (c.2898-1G>A). All mutations were located within the
      protein kinase domain of CDK13. The affected amino acids are highly conserved,
      and in silico analyses including comparative protein modelling predict that they
      will interfere with protein function. The location of the missense mutations in a
      key catalytic domain suggests that they are likely to cause loss of catalytic
      activity but retention of cyclin K binding, resulting in a dominant negative mode
      of action. Although the splice-site mutation was predicted to produce a stable
      internally deleted protein, this was not supported by expression studies in
      lymphoblastoid cells. A loss of function contribution to the underlying
      pathological mechanism therefore cannot be excluded, and the clinical
      significance of this variant remains uncertain. CONCLUSIONS: These patients
      demonstrate that heterozygous, likely dominant negative mutations affecting the
      protein kinase domain of the CDK13 gene result in a recognisable, syndromic form
      of intellectual disability, with or without congenital heart disease.

PMID- 29021402
TI  - HIV-Exposed Infants Vaccinated with an MF59/Recombinant gp120 Vaccine Have Higher
      Magnitude Anti-V1V2 IgG Responses than Adults Immunized with the Same Vaccine.
AB  - In the RV144 vaccine trial, IgG responses against the HIV envelope variable loops
      1 and 2 (V1V2) were associated with decreased HIV acquisition risk. We previously
      reported that infants immunized with an MF59-adjuvanted rgp120 vaccine developed
      higher-magnitude anti-V1V2 IgG responses than adult RV144 vaccinees. To determine
      whether the robust antibody response in infants is due to differences in vaccine
      regimens or to inherent differences between the adult and infant immune systems,
      we compared Env-specific IgG responses in adults and infants immunized with the
      same MF59- and alum-adjuvanted HIV envelope vaccines. At peak immunogenicity, the
      magnitudes of the gp120- and V1V2-specific IgG responses were comparable between
      adults and infants immunized with the alum/MNrgp120 vaccine (gp120 median
      fluorescence intensities [FIs] in infants = 7,118 and in adults = 11,510, P =
      0.070; V1V2 median MFIs of 512 [infants] and 804 [adults], P = 0.50), whereas
      infants immunized with the MF59/SF-2 rgp120 vaccine had higher-magnitude antibody
      levels than adults (gp120 median FIs of 15,509 [infants] and 2,290 [adults], P <
      0.001; V1V2 median FIs of 23,926 [infants] and 1,538 [adults]; P < 0.001). Six
      months after peak immunogenicity, infants maintained higher levels Env-specific
      IgG than adults. Anti-V1V2 IgG3 antibodies that were associated with decreased
      HIV-1 risk in RV144 vaccinees were present in 43% of MF59/rgp120-vaccinated
      infants but only in 12% of the vaccinated adults (P = 0.0018). Finally, in
      contrast to the rare vaccine-elicited Env-specific IgA in infants, rgp120 vaccine
      elicited Env-specific IgA was frequently detected in adults. Our results suggest
      that vaccine adjuvants differently modulate gp120-specific antibody responses in
      adults and infants and that infants can robustly respond to HIV Env
      immunization.IMPORTANCE More than 150,000 pediatric HIV infections occur yearly,
      despite the availability of antiretroviral prophylaxis. A pediatric HIV vaccine
      could reduce the number of these ongoing infant infections and also prime for
      long-term immunity prior to sexual debut. We previously reported that
      immunization of infants with an MF59-adjuvanted recombinant gp120 vaccine induced
      higher-magnitude, potentially protective anti-V1V2 IgG responses than in adult
      vaccinees receiving the moderately effective RV144 vaccine. In the present study,
      we demonstrate that the robust response observed in infants is not due to
      differences in vaccine regimen or vaccine dose between adults and infants. Our
      results suggest that HIV vaccine adjuvants may differentially modulate immune
      responses in adults and infants, highlighting the need to conduct vaccine trials
      in pediatric populations.

PMID- 29021400
TI  - Human Parvovirus Infection of Human Airway Epithelia Induces Pyroptotic Cell
      Death by Inhibiting Apoptosis.
AB  - Human bocavirus 1 (HBoV1) is a human parvovirus that causes acute respiratory
      tract infections in young children. In this study, we confirmed that, when
      polarized/well-differentiated human airway epithelia are infected with HBoV1 in
      vitro, they develop damage characterized by barrier function disruption and cell
      hypotrophy. Cell death mechanism analyses indicated that the infection induced
      pyroptotic cell death characterized by caspase-1 activation. Unlike infections
      with other parvoviruses, HBoV1 infection did not activate the apoptotic or
      necroptotic cell death pathway. When the NLRP3-ASC-caspase-1 inflammasome-induced
      pathway was inhibited by short hairpin RNA (shRNA), HBoV1-induced cell death
      dropped significantly; thus, NLRP3 mediated by ASC appears to be the pattern
      recognition receptor driving HBoV1 infection-induced pyroptosis. HBoV1 infection
      induced steady increases in the expression of interleukin 1alpha (IL-1alpha) and
      IL-18. HBoV1 infection was also associated with the marked expression of the
      antiapoptotic genes BIRC5 and IFI6 When the expression of BIRC5 and/or IFI6 was
      inhibited by shRNA, the infected cells underwent apoptosis rather than
      pyroptosis, as indicated by increased cleaved caspase-3 levels and the absence of
      caspase-1. BIRC5 and/or IFI6 gene inhibition also significantly reduced HBoV1
      replication. Thus, HBoV1 infection of human airway epithelial cells activates
      antiapoptotic proteins that suppress apoptosis and promote pyroptosis. This
      response may have evolved to confer a replicative advantage, thus allowing HBoV1
      to establish a persistent airway epithelial infection. This is the first report
      of pyroptosis in airway epithelia infected by a respiratory virus.IMPORTANCE
      Microbial infection of immune cells often induces pyroptosis, which is mediated
      by a cytosolic protein complex called the inflammasome that senses microbial
      pathogens and then activates the proinflammatory cytokines IL-1 and IL-18. While
      virus-infected airway epithelia often activate NLRP3 inflammasomes, studies to
      date suggest that these viruses kill the airway epithelial cells via the
      apoptotic or necrotic pathway; involvement of the pyroptosis pathway has not been
      reported previously. Here, we show for the first time that virus infection of
      human airway epithelia can also induce pyroptosis. Human bocavirus 1 (HBoV1), a
      human parvovirus, causes lower respiratory tract infections in young children.
      This study indicates that HBoV1 kills airway epithelial cells by activating genes
      that suppress apoptosis and thereby promote pyroptosis. This strategy appears to
      promote HBoV1 replication and may have evolved to allow HBoV1 to establish
      persistent infection of human airway epithelia.

PMID- 29021405
TI  - High prevalence of high-risk HPV genotypes other than 16 and 18 in cervical
      cancers of Curacao: implications for choice of prophylactic HPV vaccine.
AB  - BACKGROUND: Curacao is a Dutch-Caribbean Island located in a high-risk area for
      cervical cancer.Prior to introduction of a prophylactic human papillomavirus
      (HPV) vaccine, knowledge of the prevalence of high-risk HPV vaccine genotypes
      (HPV16, 18, 31, 33, 45, 52 and 58) in cervical (pre)cancer is required.
      OBJECTIVE: To investigate the prevalence of HPV genotypes in invasive cervical
      cancers (ICC) and cervical intraepithelial neoplasia (CIN) grade 1, 2 and 3 in
      Curacao. METHODS: Paraffin-embedded blocks of 104 cervical cancers (89 squamous,
      15 adenocarcinoma), 41 CIN3, 39 CIN2 and 40 CIN1 lesions were analysed for the
      presence of HPV. Sections were stained by H&E for histopathological evaluation,
      and DNA was extracted using proteinase K. HPV genotypes were detected using Short
      PCR Fragment (SPF10) PCR DNA enzyme immunoassay and a Line Probe Assay (LiPA25) .
      RESULTS: HPV was found in 92 (88.5%) ICC; 87 (94.6%) had a single HPV infection
      and 86 (93.5%) were high-risk human papillomavirus (hrHPV)-type positive.The
      three most common HPV types in ICC were 16 (38.5%), 18 (13.5%) and 45 (6.7%),
      covering 58.7%.HrHPV vaccine genotypes 16, 18, 31, 35, 45, 52 and 58 were
      responsible for 73.1% of ICC. For precancerous lesions, the HPV attribution was
      85.4% for CIN3, 66.7% for CIN2% and 42.5% for CIN1. CONCLUSIONS: Our study, the
      largest in the Caribbean region in (pre)cancer, shows that the prevalence of HPV
      type 16 and 18 in cervical cancer is lower compared with the world population but
      no differences in prevalence of these two HPV types are seen in precancerous
      lesions.When considering HPV vaccination in Curacao, the relatively high
      contribution of non-HPV 16/18 genotypes in ICC should be taken into account.

PMID- 29021406
TI  - Whole genome sequencing of Neisseria gonorrhoeae reveals transmission clusters
      involving patients of mixed HIV serostatus.
AB  - OBJECTIVES: Prevention and control of gonorrhoea depends on understanding the
      nature of sexual networks and risk factors for infection. We aimed to use high
      resolution typing (whole genome sequencing (WGS)) of Neisseria gonorrhoeae
      isolates plus patient questionnaire data to gain insights into transmission
      patterns in a high prevalence setting. METHODS: During a 9-month period (July
      2014-March 2015), patients diagnosed with gonorrhoea attending sexual health
      service in Brighton, UK, were invited to provide anonymised detailed information
      by questionnaire about risk factors for infection. Questionnaire data plus WGS
      data from cultured isolates were analysed to yield information about sexual
      networks and risk factors for infection. RESULTS: 104/149 individuals who
      consented to participate in the study were culture positive. 97/104 (93%) were
      male. 80 self-reported to be men who have sex with men (MSM). 35/104 (34%) of
      patients were HIV positive. 51/104 (49%) individuals reported using geosocial
      networking applications to facilitate contact. Sex under the influence of drugs
      was reported by 16/34 (46%) of HIV-positive MSM, 17/41 (41%) of HIV-negative MSM
      and 5/15 (31%) of heterosexuals. WGS data were available for 100 isolates from 83
      patients. 55 isolates (66%) belonged to genetically related subtypes involving
      one or more patients, who could be plausibly linked through recent direct or
      indirect transmission. Four transmission clusters containing 3-12 individuals
      were composed of MSM of mixed HIV serostatus. CONCLUSIONS: We show that data
      obtained from WGS of N. gonorrhoeae and enhanced epidemiological data obtained
      from patient questionnaires are mutually supportive and reveal insights into
      sexual networks. Our findings suggest that serosorting may have declined as a
      practice and indicate the importance of designing public health interventions
      that target infection risks associated with recreational drug use and contact
      made using geosocial networking applications.

PMID- 29021407
TI  - Antimicrobial susceptibility profile of Neisseria gonorrhoeae isolated in
      Cotonou, Benin (2015-2017).

PMID- 29021409
TI  - HIV-1 viral load and resistance in genital secretions in patients taking protease
      inhibitor-based second-line therapy in Africa.
AB  - BACKGROUND: HIV is transmitted primarily through sexual intercourse, and the
      objective of this study was therefore to assess whether there is occult viral
      replication and resistance in genital secretions in patients on protease
      inhibitor (PI)-based second-line therapy. METHODS: HIV-infected adults taking
      ritonavir-boosted lopinavir with either two nucleoside reverse transcriptase
      inhibitors (NRTIs), raltegravir or as monotherapy for 96 weeks, were enrolled at
      seven clinical sites in Uganda. Viral load (VL) was measured in cervico-vaginal
      secretions or semen and in a corresponding plasma sample. Genotypic resistance
      was assessed in genital secretion samples and plasma samples. Results were
      compared between compartments and with the plasma resistance profile at first
      line failure. RESULTS: Of the 111 participants enrolled (91 female, 20 male), 16
      (14%) and 30 (27%) had VL >1,000 and >40 copies/ml, respectively, in plasma; 3
      (3%) and 23 (21%) had VL >1,000 copies/ml and >40 copies/ml, respectively, in
      genital secretions. There was 74% agreement between plasma and genital secretion
      VL classification above/below 40 copies/ml threshold (kappa-statistic =0.29;
      P=0.001). RT mutations (both NRTI and non-nucleoside reverse transcriptase
      inhibitor) were detected in genital secretions in four patients (similar profile
      to corresponding plasma sample at first-line failure) and PI mutations were
      detected in two (one polymorphism with no impact on resistance; one with high
      level PI resistance). CONCLUSIONS: High level (>1,000 copies/ml) viral
      replication and development of new RT or PI resistance in the genital compartment
      were rare. The risks of transmission arising from resistance evolution in the
      genital compartment are likely to be low on PI-based second-line therapy.

PMID- 29021410
TI  - William Jackson ('Jack') Schull (1922-2017).

PMID- 29021408
TI  - Repeat syphilis has a different immune response compared with initial syphilis:
      an analysis of biomarker kinetics in two cohorts.
AB  - OBJECTIVE: We aimed to asses if there are differences in the clinical
      presentation and immune response of repeat as compared with initial syphilis.
      METHODS: Prospective study: we prospectively recruited all patients with a new
      diagnosis of syphilis and tested their plasma for a range of cytochemokines and
      rapid plasma reagin (RPR) at baseline pretreatment and 6 months following
      therapy. Retrospective study: we compared RPR assay response kinetics between
      initial and repeat syphilis in persons attending our HIV/STI clinic from 1993 to
      2016. RESULTS: Prospective study: a total of 91 individuals, 36 with initial
      syphilis and 55 with repeat syphilis, were included in the study. At baseline
      visit, those with initial syphilis were more likely to be symptomatic and have
      higher levels of interleukin-10 than repeaters. At baseline, median RPR titres
      were higher in the repeat than the initial infection groups. Repeaters were less
      likely than those with initial infections to serorevert to a negative RPR and be
      serofast (<4-fold RPR titre decline) at 6 months.Retrospective study: syphilis
      was diagnosed in 1027/43 870 individuals tested. At diagnosis, repeaters had
      higher RPR titres and a stepwise increase in RPR titre with number of syphilis
      episodes. They had a different RPR test response kinetic: they were less likely
      to be serofast and to serorevert than initial syphilis at 6 and 12 months. No
      individuals with four or more previous episodes of syphilis seroreverted.
      CONCLUSION: Repeat syphilis has a different clinical presentation and
      immunological response to initial infection.

PMID- 29021411
TI  - Biomaterials for corneal bioengineering.
AB  - Corneal transplantation is an important surgical treatment for many common
      corneal diseases. However, a worldwide shortage of tissue from suitable corneal
      donors has meant that many people are not able to receive sight-restoring
      operations. In addition, rejection is a major cause of corneal transplant
      failure. Bioengineering corneal tissue has recently gained widespread attention.
      In order to facilitate corneal regeneration, a range of materials is currently
      being investigated. The ideal substrate requires sufficient tectonic durability,
      biocompatibility with cultured cellular elements, transparency, and perhaps
      biodegradability and clinical compliance. This review considers the anatomy and
      function of the native cornea as a precursor to evaluating a variety of
      biomaterials for corneal regeneration including key characteristics for optimal
      material form and function. The integration of appropriate cells with the most
      appropriate biomaterials is also discussed. Taken together, the information
      provided offers insight into the requirements for fabricating synthetic and
      semisynthetic corneas for in vitro modeling of tissue development and disease,
      pharmaceutical screening, and in vivo application for regenerative medicine.

PMID- 29021412
TI  - Postoperative Headache after Undergoing Acoustic Neuroma Surgery via the
      Retrosigmoid Approach.
AB  - To estimate the duration of postoperative headache after surgery for acoustic
      neuroma and the effects of age, sex, tumor size, extent of tumor resection, type
      of skin incision, surgical duration, hearing preservation, and postoperative
      facial nerve palsy. This retrospective review analyzed clinical data from 97
      patients who had undergone surgery for unilateral acoustic neuroma via the
      retrosigmoid approach >1 year previously. We investigated whether patients had
      headache at hospital discharge and during attendance at outpatient clinics. We
      classified postoperative headache as grade 0 (no headache), 1 (tolerable headache
      without medication), or 2 (headache requiring medication). The period of headache
      was defined as the interval in days between surgery and achievement of grade 0.
      The period of medication for headache was defined as the interval in days between
      surgery and achievement of grade 0 or 1. Kaplan-Meier analysis revealed median
      durations of medication and headache of 81 and 641 days, respectively. Headache
      was cured significantly earlier in patients who underwent surgery using a C-type
      skin incision (P < 0.001). Headache persisted significantly longer among patients
      who underwent a shorter surgical procedure (P < 0.02). Multivariate analysis
      confirmed the type of skin incision as a factor independently associated with
      duration of postoperative headache. Postoperative headache was cured in the
      majority of patients within about 2 years after surgery. The C-type skin incision
      is likely beneficial for reducing the duration of postoperative headache,
      although headache persisted in a small number of patients.

PMID- 29021414
TI  - Development of bioassay system for evaluation of materials for personal
      protective equipment (PPE) against toxic effects of ionizing radiations.
AB  - Health effects caused by ionizing radiations raise considerable concern among
      general public and radiation workers. To estimate ability of personal protective
      equipment (PPE) materials that reduce toxic effects of ionizing radiations, we
      developed an experimental bioassay system using Chinese Hamster V79 cells. The
      system developed here distinguished the biological effectiveness of X-ray that
      was significantly affected by elements composed of shielding materials. Survival
      of the cells exposed to sub-lethal dose of X-ray was enhanced more than 2 times
      when the X-ray was filtrated by a lead plate. Also filtration of the X-ray with a
      tungsten plate enhanced the cell survival more than three times. These results
      suggested the colony assay system developed here was useful for examination of
      the biological effectiveness of X-ray and the ability of PPE materials reducing
      the toxic effects caused by ionizing radiations.

PMID- 29021413
TI  - CyberKnife Stereotactic Radiosurgery and Hypofractionated Stereotactic
      Radiotherapy As First-line Treatments for Imaging-diagnosed Intracranial
      Meningiomas.
AB  - Definitive radiotherapy is an important alternative treatment for meningioma
      patients who are inoperable or refuse surgery. We evaluated the efficacy and
      toxicity of CyberKnife-based stereotactic radiosurgery (SRS) and hypofractionated
      stereotactic radiotherapy (hSRT) as first-line treatments for intracranial
      meningiomas that were diagnosed using magnetic resonance imaging (MRI) and/or
      computed tomography (CT). Between February 2005 and September 2015, 41 patients
      with intracranial meningiomas were treated with CyberKnife-based SRS or hSRT.
      Eleven of those tumors were located in the skull base. The median tumor volume
      was 10.4 ml (range, 1.4-56.9 ml). The median prescribed radiation dose was 17 Gy
      (range, 13-20 Gy to the 61-88% isodose line) for SRS (n = 9) and 25 Gy (range, 14
      38 Gy to the 44-83% isodose line) for hSRT (n = 32). The hSRT doses were
      delivered in 2 to 10 daily fractions. The median follow-up period was 49 months
      (range, 7-138). The 5-year progression-free survival rate (PFS) for all 41
      patients was 86%. The 3-year PFS was 69% for the 14 patients with tumor volumes
      of >=13.5 ml (30 mm in diameter) and 100% for the 27 patients with tumor volumes
      of <13.5 ml (P = 0.031). Grade >2 toxicities were observed in 5 patients (all of
      them had tumor volumes of >=13.5 ml). SRS and hSRT are safe and effective against
      relatively small (<13.5 ml) meningiomas.

PMID- 29021415
TI  - Cerebrovascular/cardiovascular diseases and mental disorders due to overwork and
      work-related stress among local public employees in Japan.
AB  - In Japan, overwork-related disorders occur among local public employees as well
      as those in private businesses. However, to date, there are no studies reporting
      the state of compensation for cerebrovascular/cardiovascular diseases (CCVD) and
      mental disorders due to overwork or work-related stress among local public
      employees in Japan over multiple years. This report examined the recent trend of
      overwork-related CCVD and mental disorders, including the incidence rates of
      these disorders, among local public employees in Japan from the perspective of
      compensation for public accidents, using data from the Japanese Government and
      relevant organizations. Since 2000, compared to CCVD, there has been an overall
      increase in the number of claims and cases of compensation for mental disorders.
      Over half of the individuals receiving compensation for mental disorders were
      either in their 30s or younger. About 47% of cases of mental disorders were
      compensated due to work-related factors other than long working hours. The
      incidence rate by job type was highest among "police officials" and "fire
      department officials" for compensated CCVD and mental disorders cases,
      respectively. Changes in the trend of overwork-related disorders among local
      public employees in Japan under a legal foundation should be closely monitored.

PMID- 29021416
TI  - Thermal comfort sustained by cold protective clothing in Arctic open-pit mining-a
      thermal manikin and questionnaire study.
AB  - Workers in the Arctic open-pit mines are exposed to harsh weather conditions.
      Employers are required to provide protective clothing for workers. This can be
      the outer layer, but sometimes also inner or middle layers are provided. This
      study aimed to determine how Arctic open-pit miners protect themselves against
      cold and the sufficiency, and the selection criteria of the garments. Workers'
      cold experiences and the clothing in four Arctic open-pit mines in Finland,
      Sweden, Norway and Russia were evaluated by a questionnaire (n=1,323). Basic
      thermal insulation (Icl) of the reported clothing was estimated (ISO 9920). The
      Icl of clothing from the mines were also measured by thermal manikin
      (standing/walking) in 0.3 and 4.0 m/s wind. The questionnaire showed that the Icl
      of the selected clothing was on average 1.2 and 1.5 clo in mild (-5 to +5 degrees
      C) and dry cold (-20 to -10 degrees C) conditions, respectively. The Icl of the
      clothing measured by thermal manikin was 1.9-2.3 clo. The results show that the
      Arctic open-pit miners' selected their clothing based on occupational (time
      outdoors), environmental (temperature, wind, moisture) and individual factors
      (cold sensitivity, general health). However, the selected clothing was not
      sufficient to prevent cooling completely at ambient temperatures below -10
      degrees C.

PMID- 29021417
TI  - Miniaturized Leadless Cardiac Pacemakers - Can They Overcome the Problems With
      Transvenous Pacing Systems?

PMID- 29021418
TI  - Chronic Obstructive Pulmonary Disease and Atherosclerosis - Warning From the
      Hisayama Study.

PMID- 29021419
TI  - What Should Be Generalized Diagnostic Markers for Peripartum Cardiomyopathy?

PMID- 29021420
TI  - Relationships between neighborhood attributes and subjective well-being among the
      Chinese elderly: Data from Shanghai.
AB  - It has been hypothesized that subjective well-being (SWB) is determined by a
      combination of individual characteristics, social environment, and physical
      environment. However, few studies have simultaneously examined the relationships
      of the social and physical attributes of a neighborhood with SWB. Accordingly,
      the present study aimed to examine these relationships among Chinese elders. A
      total of 2,719 elders aged 60 years or older were recruited from 47 neighborhoods
      in the Xinhua subdistrict of Shanghai by two-stage stratified random sampling and
      interviewed between July and September 2014. The social and physical attributes
      of each neighborhood were assessed using validated and psychometrically tested
      measures. The Chinese version of the international Personal Wellbeing Index was
      used to assess SWB. Control variables included sex, age, marital status,
      education level, years living in the neighborhood, self-rated health, chronic
      conditions, and leisure-time physical activity. Multilevel linear regression
      analysis was conducted to explore whether social and physical attributes were
      associated with SWB. The average level of SWB was 74.2 +/- 15.7% of the scale
      maximum. After controlling for individual covariates, individual-level social
      cohesion and social interaction were positively correlated with SWB, and both
      individual-level and neighborhood-level aesthetic quality was positively
      correlated with SWB. In conclusion, both social and physical attributes of
      neighborhoods were associated with SWB among Chinese elderly. These findings
      suggest that creating aesthetic and cohesive neighborhoods may encourage Chinese
      elders to participate in social activities and promote their SWB.

PMID- 29021421
TI  - Indication for surgical resection in patients with hepatocellular carcinoma with
      major vascular invasion.
AB  - Major portal vein invasion (MVI) by hepatocellular carcinoma (HCC) carries an
      extremely poor prognosis. Our aim was to clarify the indications of hepatic
      resection in the presence of MVI by HCC. Between 2001 and 2015, 1,306 patients
      undergoing primary treatment for HCC were analyzed (866 hepatic resections and
      440 transarterial therapies). Significant prognostic factors were identified by
      retrospectively analyzing tumor status, liver function and treatment. Overall
      survival was compared in terms of the degree of vascular invasion and treatment.
      The 5-year survival rates according to the degree of vascular invasion (Vp) were
      Vp0: 51.9%, Vp1: 33.0%, Vp2: 16.7%, Vp3: 21.8%, and Vp4: 0%, respectively.
      Overall survival (OS) did not differ significantly between patients with Vp3 and
      Vp4 MVI (p = 0.153). Median survival following hepatic resection of Vp3 cases was
      significantly better than that for Vp4 cases (1,913 vs. 258 days, p = 0.014),
      while OS following transarterial therapy was not significantly different (164 vs.
      254 days in Vp3 vs. Vp4, p = 0.137). Multivariate analysis revealed hepatic
      resection (Odds: 2.335 [95%CI: 1.236-4.718], p = 0.008) and multiple tumors
      (1.698 [1.029-2.826], p = 0.038) as independent predictors of survival. Hepatic
      resection in HCC patients with MVI should be indicate in patients with Vp3
      invasion.

PMID- 29021422
TI  - Non-linear association between alcohol and incident frailty among community
      dwelling older people: A dose-response meta-analysis.
AB  - A recent systematic review and meta-analysis study suggested that higher alcohol
      consumption is associated with lower risks for frailty. However the apparent
      protective effect may not be true because of some limitations. Therefore we
      further explored potential linear and non-linear associations using a two-stage
      dose-response meta-analysis. Restricted cubic splines were applied with three
      fixed knots at percentiles (10%, 50%, and 90%). A two-stage dose-response meta
      analysis showed a significant non-linear association (p for non-linearity <
      0.001); incident frailty risk decreased until around 15 g/day of alcohol
      consumption and increased thereafter. This suggests that while moderate alcohol
      consumption is associated with a lower risk of frailty, at higher consumption
      levels this apparent protect effect is lost. Given these findings, non-linear
      associations should be considered in future research on alcohol and frailty.

PMID- 29021423
TI  - Should We Include a Defibrillator for All Cardiac Resynchronization Therapy? -
      Comparison of Cardiac Resynchronization Therapy Without and With Defibrillation.

PMID- 29021424
TI  - Detection and molecular characterization of equine infectious anemia virus in
      Mongolian horses.
AB  - The genetic characterization and actual prevalence of EIAV in Mongolian horse in
      the disease endemic region is currently unknown. Here, 11 of 776 horse serum
      samples from four Mongolian provinces tested positive on agar gel immunodiffusion
      test. Genomic DNA extracted from all seropositive samples was subjected to nested
      PCR assay. Among these, three samples tested positive with nested PCR assay and
      were identified by sequencing analysis based on long termination repeat and tat
      gene of the virus. Two of the three sequences were identical, with 94.0% identity
      with the third. These two independent Mongolian EIAV sequences were retained
      functional motifs, with no dramatic changes but some variability in the U5
      region; they were clustered with genotypes from European countries but not with
      those from China, U.S.A., or Japan.

PMID- 29021425
TI  - A cat with suspected laryngeal metastasis with mucosal irregularity resulting
      from apocrine/salivary gland adenocarcinoma in the head.
AB  - A 16-year-old castrated male mongrel cat presented with swelling under the left
      pinna and a 3 -month history of voice change. Laryngeal endoscopy revealed
      circumferential oedema around the arytenoid cartilages and hypersecretion of
      saliva. Histopathological examination of the mass around the left ear canal was
      considered the primary lesion that originated from cutaneous apocrine
      adenocarcinoma or parotid gland adenocarcinoma, and it metastasized to the
      larynx, lung and medial retropharyngeal lymph nodes. This report provides new
      insights into feline laryngeal diseases which could result in laryngeal
      metastasis with slight mucosal irregularity alone and without obvious
      radiographic abnormalities. Therefore, histopathological examination should be
      performed when a cat presents clinical signs such as stridor, dysphonia or voice
      change without any mass-forming laryngeal lesion.

PMID- 29021427
TI  - Petrified Ear Auricles with Isolated Adrenocorticotropic Hormone Deficiency.

PMID- 29021426
TI  - Natural larval Echinococcus multilocularis infection in a Norway rat, Rattus
      norvegicus, captured indoors in Hokkaido, Japan.
AB  - Natural infection with larval Echinococcus multilocularis was recognized in one
      of eight Norway rats, Rattus norvegicus, caught indoors in 2009 in Ebetsu,
      Hokkaido, northern Japan. Cystic lesions were found in the right median and
      lateral lobes of the liver, with numerous alveolar cysts in the periphery of the
      lesions. Protoscolices were formed within large cysts. The laminated layers of
      the cysts were positive for PAS staining. Nested PCR using the primers specific
      for Taenia mitochondrial 12S rDNA yielded a 250-bp product, and the sequence of
      the PCR product matched that of E. multilocularis isolates from Hokkaido and
      Germany. This is the third natural alveolar hydatidosis in R. norvegicus in
      Japan.

PMID- 29021428
TI  - Changes in the Clinical Features and Long-term Outcomes of Colonic Diverticulitis
      in Japanese Patients.
AB  - Objective The purpose of this study was to investigate whether changes occurred
      in the clinical features of acute colonic diverticulitis (ACD) over a period of
      10 years, to estimate the long-term probability of disease recurrence and to
      investigate whether it could be treated in an outpatient setting. Methods Between
      January 1998 and January 2009, 488 ACD patients were diagnosed and treated in
      Saiseikai Central Hospital, Tokyo. The diagnoses were made by ultrasonography
      (US) and/or CT. We investigated the time-dependent changes in the characteristics
      of patients with ACD, and we used the Kaplan-Meier method to estimate the
      cumulative probability of recurrence, based on information from a questionnaire.
      Results The percentage of patients who were diagnosed with left-sided ACD
      significantly increased over time in comparison to those with right-side disease
      (4% in 1998, 36% in 2009). Patients with left-sided ACD were significantly older
      and were diagnosed at a more advanced disease stage than those with right-sided
      ACD. Among the 212 ACD patients who responded to the questionnaire, the
      cumulative probability of recurrence in 125 patients with no history of ACD at
      2.9, 5.9 and 10.1 years was 16.0%, 20.1% and 26.2%, respectively. The probability
      of recurrence in patients with right-sided and left-sided ACD did not differ to a
      statistically significant extent. In addition, outpatient treatability in
      patients with left-sided to right-sided ACD did not differ to a statistically
      significant extent (66.6% vs. 70.1%). Conclusion The ratio of left-sided to right
      sided ACD was found to have increased over the past decade. Left-sided ACD
      patients were older and their incidence of complications was higher in comparison
      to right-sided patients; however, the rate of recurrence and outpatient
      treatability in patients with left-sided and right-sided ACD did not differ to a
      statistically significant extent.

PMID- 29021429
TI  - Sclerosing Esophagitis with IgG4-positive Plasma Cell Infiltration.
AB  - The patient was a 76-year-old woman who had noticed slight difficulty in
      swallowing in the 3 years prior to this presentation. Her dysphagia progressed
      while she was hospitalized following cervical cancer surgery.
      Esophagogastroduodenoscopy and an esophagram showed circumferential erosion and a
      stricture of the thoracic esophagus. Esophageal resection was performed; the
      resected specimens showed a stricture and wall thickening. Histologically,
      transmural hyperplasia, which consisted of inflammatory granulation tissue with
      the abundant infiltration of IgG4-positive plasma cells and lymphocytes, was
      observed. The patient was diagnosed with probable IgG4-related disease. IgG4
      related esophageal disease presenting as esophageal lesions alone is a very rare
      condition.

PMID- 29021430
TI  - Crizotinib-induced Rectal Perforation with Abscess.
AB  - An 86-year-old Japanese man was diagnosed with stage IV lung adenocarcinoma. The
      patient was treated with crizotinib after echinoderm microtubule-associated
      protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangement was detected
      from his pleural effusion. He subsequently developed abdominal pain and rebound
      tenderness in the right lower abdomen. Contrast-enhanced abdominal CT showed a
      low-density area in the abdominal cavity. The size of the abscess was decreased
      by drainage and the administration of antibiotics. Fistulography revealed a
      fistula from the rectum to the abscess, and a diagnosis of lower intestinal tract
      perforation with abscess formation was made. Crizotinib was discontinued and
      treatment with alectinib was initiated. The patient remains under treatment as an
      outpatient at our department without adverse effects.

PMID- 29021431
TI  - Tocilizumab-resistant TAFRO Syndrome Complicated by Type II Respiratory Failure.
AB  - A 66-year-old man with a several year history of thrombocytopenia, pleural
      effusion and ascites, anasarca, and organomegaly presented with general fatigue,
      appetite loss, dyspnea with type II respiratory failure. The precise history of
      the patient and the re-evaluation of lymph node and bone marrow biopsies
      conducted by the previous physician indicated TAFRO syndrome. The patient's
      laboratory data improved for a year with tocilizumab, but then worsened to the
      point that the patient required artificial ventilation due to the deterioration
      of type II respiratory failure. The replacement of tocilizumab with rituximab
      yielded a steady improvement, but it was necessary to address the patient's
      persistent respiratory failure. Peripheral nerve disorder might have been
      involved with the patient's respiratory failure.

PMID- 29021432
TI  - Prediction of Disseminated Intravascular Coagulation by Liver Function Tests in
      Patients with Japanese Spotted Fever.
AB  - Objective Cases of Japanese spotted fever (JSF) are sometimes complicated by
      disseminated intravascular coagulation (DIC) with an abnormal liver function,
      resulting in unfavorable outcomes. The aim of the present study was to clarify
      the correlation between liver function test results and DIC scores. Methods
      Twenty patients diagnosed with JSF between April 2010 and April 2014 were
      enrolled. Age, gender, disturbance of consciousness, body temperature, pulse
      rate, presence of diffuse erythema, eschar and swelling of lymph nodes,
      laboratory test results at the time of initial presentation such as blood cell
      count, C-reactive protein, liver function, renal function and blood coagulation
      and fibrinolysis, maximum Japanese Association for Acute Medicine (JAAM) DIC
      score during the course of JSF, treatment and the prognosis were retrospectively
      reviewed. Results The median age of the patients (8 men, 12 women) was 68.3
      years. There were significant differences in the alkaline phosphatase (ALP) and
      rothrombin time international normalized ratio (PT-INR) between the DIC and non
      DIC groups using Mann-Whitney's U test. A multiple logistic regression analysis
      showed that the ALP and blood urea nitrogen (BUN) levels at the time of initial
      presentation were independent predictors of the occurrence of DIC. Conclusion We
      should pay special attention to JSF patients showing high levels of ALP at the
      initial presentation, since such patients may have a higher likelihood of
      developing DIC over the course of JSF and unfavorable outcomes than those with
      lower levels.

PMID- 29021433
TI  - Secondary Syphilis with Pulmonary Involvement.
AB  - A 39-year-old Japanese man presented to our hospital complaining of left chest
      pain and rash on the hands and feet. Plain thoracic computed tomography (CT)
      revealed multiple nodular shadows in the left lower lobe of the lung. A diagnosis
      of secondary syphilis was made based on the appearance of the rash and positive
      serologic tests for syphilis. The patient was started on amoxicillin but was
      switched to minocycline due to amoxicillin-induced rash on both forearms.
      Thoracic CT after five months of treatment revealed that the multiple lung
      nodular shadows had contracted, and secondary syphilis with pulmonary involvement
      was diagnosed.

PMID- 29021434
TI  - Effectiveness of Bare Metal Stent Implantation for the Treatment of Coronary
      Artery Aneurysm: A Multimodality Imaging Evaluation.
AB  - Coronary artery aneurysm (CAA) after sirolimus-eluting stent (SES) implantation
      is one of the most troublesome problems associated with first-generation drug
      eluting stents. However, the natural course and standard therapy of CAA has been
      unknown. A 49-year-old man underwent SES implantation for the left anterior
      descending artery. Follow-up coronary angiography (CAG) revealed CAA in the SES.
      We performed bare metal stent (BMS) implantation for treatment of CAA. Ten months
      after the BMS implantation, the size of the CAA had diminished, and a very thin
      layer of endothelium on the BMS was observed by optical coherence tomography. CAG
      assessment revealed that the blood stream of the CAA had been obstructed. We
      herein report a case of CAA after SES implantation with eight years of follow-up
      and the findings of a multimodality imaging evaluation.

PMID- 29021435
TI  - Hyponatremia with Loss of High Signal Intensity in the Posterior Pituitary Lobe
      on T1-weighted Magnetic Resonance Imaging.
AB  - Herein, we report on an 82-year-old woman who presented with anorexia. The
      patient had hyponatremia with preserved urinary osmotic pressure. T1-weighted
      magnetic resonance imaging (MRI) showed a lack of high signal intensity (SI) in
      the posterior pituitary lobe. Based on the patient's high levels of N-terminal
      prohormone of brain natriuretic peptide (NT-proBNP), heart failure was suspected.
      The heart failure may have caused arginine vasopressin (AVP) secretion. The
      depletion of AVP secretory granules may therefore cause the posterior pituitary
      gland to disappear on T1-weighted MRI.

PMID- 29021436
TI  - Multiple Myeloma Presenting with Autoimmune Autonomic Ganglionopathy.
AB  - Autoimmune autonomic ganglionopathy is an autonomic disorder that occurs as a
      symptom of paraneoplastic neurological syndrome. To date, there have been no
      reports on multiple myeloma with autoimmune autonomic ganglionopathy. A 37-year
      old Japanese woman suffered from orthostatic hypotension was diagnosed with
      multiple myeloma (IgG kappa type), and a serological examination revealed the
      presence of anti-ganglionic nicotinic acetylcholine receptor (anti-gAChR)
      antibodies. She was treated for multiple myeloma, as a result, the autonomic
      disturbance improved and her anti-gAChR antibody titer decreased to undetectable
      levels, despite the fact that she only achieved a partial remission of multiple
      myeloma. Treatment for multiple myeloma may improve autoimmune autonomic
      ganglionopathy.

PMID- 29021437
TI  - A Systematic Review of the Effectiveness of Antianxiety and Antidepressive Agents
      for Functional Dyspepsia.
AB  - Objective Functional dyspepsia (FD) is defined as persistent or recurrent pain or
      discomfort centered in the upper abdomen without organic disease. Psychosocial
      factors have been proposed as an important element in the pathophysiology of FD.
      Therefore, psychotropic agents having antianxiety or antidepressive action are
      expected to alleviate FD. We previously reported on the treatment of FD using
      such agents in a systematic review, wherein the effectiveness of the agents on FD
      was suggested, although there were several limitations. We searched for articles
      on this subject after our systematic review and re-reviewed them systematically.
      Methods Articles were searched for in MEDLINE from 2003 to 2014 using terms
      related to antianxiety or antidepressive agents. Clinical studies in which the
      effectiveness of such agents was clearly stated were selected from the retrieved
      articles. The newly selected and previously selected studies were combined, and
      statistical analyses were carried out. Results Nine studies were selected. Five
      of the studies indicated a significant symptomatic improvement using psychotropic
      drugs. A statistical analysis suggested a significant treatment effect of
      psychotropic agents having antianxiety or antidepressive action [pooled relative
      risk (PRR), 0.72; 95% confidence interval (95% CI), 0.52-0.99; p=0.0406] but did
      not show a significant benefit of treatment with agents having an antidepressive
      action alone (PRR, 0.63; 95% CI, 0.38-1.03; p=0.0665). Conclusion Our systematic
      review suggested that psychotropic drugs having antianxiety and antidepressive
      actions as a whole might be effective in alleviating FD symptoms, whereas those
      having only antidepressive action were not effective.

PMID- 29021440
TI  - Meningococcal Bursitis.

PMID- 29021438
TI  - Factors for Predicting Outcomes among Non-HIV Patients with Pulmonary
      Tuberculosis.
AB  - Objective Onodera's Prognostic Nutritional Index (PNI), determined as "10*
      albumin (g/dL) + 0.005* lymphocyte count (/MUL)," was originally designed to
      determine the risk of complications following gastrointestinal surgery. This
      single-center, retrospective observational study was designed to investigate
      whether or not the PNI can predict the treatment outcome. Methods We
      consecutively reviewed HIV-negative pulmonary tuberculosis adults in an isolation
      ward. Most patients were being treated with standard three- or four-drug
      regimens. Patients were discharged after consecutive negative smears/cultures
      were confirmed. The risk of all-cause death was assessed using a multivariable
      Cox proportional hazard model and a log-rank trend test. Results During the
      observation period, we observed 371 consecutive patients with a median age of 72
      (interquartile range [IQR]: 54-82) years. In our cohort, 295 (79.5%) patients
      were discharged alive, and 76 (20.5%) died in-hospital. Patients who died in
      hospital had a lower PNI [median 21.2 (IQR: 18.5-25.9)] than those who were
      discharged alive [median 35.1 (IQR: 28.0-43.3); p<0.001]. The area under the
      receiver operating characteristic curve was 0.87. After dividing the patients
      based on the baseline PNI quartile, those patients with a lower PNI showed a
      poorer survival than those with a higher PNI (log-rank trend p<0.001). After
      adjusting for other baseline variables, the baseline PNI was still associated
      with in-hospital death with a hazard ratio of 0.86 (95% confidence interval: 0.82
      0.91, p<0.001). Conclusion Our results showed that a low PNI was clearly related
      to a poor survival prognosis in smear-positive HIV-negative pulmonary
      tuberculosis inpatients.

PMID- 29021439
TI  - Relationship between Bath-related Deaths and Low Air Temperature.
AB  - Objective Bath-related sudden cardiac arrests occur frequently in Japan. Although
      previous studies have reported that most fatal events occurr in winter, the
      reason why such events exhibit a seasonal variation has not been elucidated. In
      this study, we hypothesized that the occurrence of bath-related deaths was
      correlated with a low air temperature. Methods This prospective cross-sectional
      observational study was conducted in the Tokyo Metropolitan area between October
      2012 and March 2013. Data were collected for all cases involving the activation
      of the emergency medical system because of an accident or acute illness related
      to bathing that occurred in Tokyo during the study period. In particular, elderly
      (>=65 years) cardiac arrest victims who had been found in a bathtub filled with
      water were enrolled. The relationship between the daily number of cardiac arrest
      events and the lowest daily air temperature in Tokyo was studied using a
      nonlinear regression model. Results A total of 3,624 bath-related events were
      registered in this study. Among these events, 1,081 deaths of elderly individuals
      who had been found in a bathtub filled with water were recorded. A close
      correlation was observed between the daily number of events and the lowest daily
      air temperature. This correlation was described by the following equation:
      y=8.38e-0.07x, where y was the daily number of cardiac arrests and x was the
      lowest daily air temperature. Conclusion A low air temperature was closely
      correlated with the occurrence of bath-related cardiac arrest.

PMID- 29021441
TI  - Steakhouse Syndrome in Myotonic Dystrophy.
AB  - A 70-year-old man with myotonic dystrophy (MD) showed repetitive vomiting and
      decreased food ingestion. These symptoms were caused by acute mass of steak
      impaction occluding the esophagus, known as "steakhouse syndrome," which may have
      occurred in response to esophageal functional changes following gastrointestinal
      involvement due to MD pathology. The occluding food was successfully removed
      endoscopically, and his symptoms resolved without relapse. Our case suggests that
      MD patients can present with "steakhouse syndrome" due to bolus food impaction
      occluding the esophagus as one of their gastrointestinal manifestations, which
      underscores the need for its consideration in MD patients presenting with similar
      symptoms.

PMID- 29021442
TI  - The Relationship between the Serum Oxytocin Levels, Disease Activity, the ADLs
      and the QOL in Patients with Rheumatoid Arthritis.
AB  - Objective To investigate the factors associated with depression, including the
      serum oxytocin (OXT) levels, disease activity, activities of daily living (ADLs)
      and quality of life (QOL), and their effects on rheumatoid arthritis (RA).
      Methods This study included 42-RA-patients. We measured the following variables
      before and after 6 months of treatment with biological disease-modifying
      antirheumatic drugs (bDMARDs): the baseline characteristics (including age, sex,
      disease duration, smoking, and body mass index), the doses of prednisolone and
      methotrexate, the serum level of matrix metalloprotease-3, the erythrocyte
      sedimentation rate and the C-reactive protein level. The disease activity of RA
      was assessed using the Simplified Disease Activity Index (SDAI), depression was
      assessed using the Hamilton Depression Rating Scale (HAM-D), the ADLs were
      assessed using the Health Assessment Questionnaire disability index and the QOL
      was assessed using the Short Form (SF)-36. The serum OXT levels were determined
      using an enzyme-linked immunosorbent assay. Results The HAM-D score was
      significantly correlated with the SDAI, and the mental component summary score of
      the SF-36. However, the serum OXT levels were not correlated with the HAM-D
      score. The serum OXT levels before and after bDMARDs treatment did not differ to
      a statistically significant extent, regardless of the presence of depression.
      Although the differences in the serum levels of OXT were observed prior to the
      initiation of treatment, there was no gender difference after treatment.
      Conclusion Although RA complicated by depression may be related to the following
      high disease activity, a poor QOL and poor ADLs, the serum OXT levels were not
      directly correlated.

PMID- 29021443
TI  - Phalangeal Microgeodic Syndrome in a Patient with Systemic Lupus Erythematosus.
AB  - We herein report a woman in her 50s with systemic lupus erythematosus (SLE) who
      developed swelling and pain in her fingers; the symptoms were more prominent in
      winter. Magnetic resonance imaging (MRI) revealed bone edema in the phalanges of
      both hands, which was compatible with phalangeal microgeodic syndrome (PMS). This
      is the first reported case of PMS in a patient with SLE and suggests that
      performing MRI should be considered for patients with SLE in order to assess the
      nature of finger symptoms and signs more precisely.

PMID- 29021444
TI  - Recurrent Kikuchi-Fujimoto Disease Successfully Treated by the Concomitant Use of
      Hydroxychloroquine and Corticosteroids.
AB  - Kikuchi-Fujimoto disease (KFD) is a benign disease of unknown etiology
      characterized by lymphadenopathy and a fever. For the majority of patients with
      KFD, the course is self-limited; however, the optimum method of managing
      recurrent cases has not yet been established. We herein report a case of a 42
      year-old Japanese woman with KFD (confirmed by a lymph node biopsy). Although
      high-dose prednisolone (PSL) rapidly induced remission, she experienced four
      recurrences on treatment tapering. Concomitant use of hydroxychloroquine (HCQ)
      with low-dose PSL induced continuous remission. This is the first case to suggest
      the effectiveness of HCQ for recurrent KFD in a Japanese patient.

PMID- 29021445
TI  - Liver Abscess and Portal Vein Thrombosis Due to Ileal Diverticulitis Mediated by
      Barium Fluoroscopy.
AB  - We report a case of liver abscess and portal vein thrombosis, which occurred due
      to diverticulitis at the terminal ileum in a 59-year-old man. The patient
      underwent a barium fluoroscopic examination 1 month before presenting to our
      hospital. He also showed liver dysfunction due to thrombosis at the superior
      mesenteric and portal veins. His inflammation gradually subsided after the
      initiation of treatment, but the recovery was not sufficient. Thus, surgery was
      performed. The patient condition improved after surgery and he was discharged.
      Barium examinations are relatively safe, but can sometimes cause severe adverse
      effects in patients with certain risk factors, and an appropriate diagnosis and
      treatment are necessary when symptoms appear.

PMID- 29021447
TI  - Acute Arthritis of the Fingers in an Elderly Woman.

PMID- 29021446
TI  - Nephrotic Syndrome and a Retroperitoneal Mass: A Case Report of a Patient with
      Recurrent Invasive Thymoma.
AB  - A 68-year-old man was admitted to our hospital to undergo an examination for
      nephrotic syndrome while concurrently complicated with recurrent thymoma in the
      parietal pleura and retroperitoneum. He had been diagnosed with invasive thymoma
      and had undergone thymo-thymectomy seven years previously. Based on the renal
      biopsy findings, his nephrotic syndrome was ascribed to minimal change disease.
      He was treated with corticosteroid monotherapy, which resulted in complete
      remission six months later, despite the fact that the recurrent thymoma remained.
      The role of thymoma in the pathogenesis of paraneoplastic glomerulopathy and the
      therapeutic concerns that emerged in this case are also discussed.

PMID- 29021448
TI  - Additional Octreotide Therapy to Sirolimus Achieved a Decrease in Sirolimus
      refractory Chylous Effusion Complicated with Lymphangioleiomyomatosis.
AB  - Recently, sirolimus, an inhibitor of mammalian target of rapamycin, was reported
      to decrease chylous effusion in patients with lymphangioleimyomatosis (LAM). We
      herein report a case of a 34-year-old woman with LAM who developed refractory
      chylothorax and chylous ascites during sirolimus therapy. In this case, to reduce
      chylous effusion, we administered octreotide, which is often used to control
      postoperative chylous effusion, in addition to the sirolimus therapy. This
      combination therapy reduced the chylothorax and chylous ascites. For patients
      with LAM, octreotide therapy in addition to sirolimus may be effective for
      treating sirolimus-refractory chylous effusion.

PMID- 29021449
TI  - Diffuse Intestinal Ganglioneuromatosis Showing Multiple Large Bowel Ulcers in a
      Patient with Neurofibromatosis Type 1.
AB  - A 67-year-old Japanese man with neurofibromatosis type 1 underwent right
      hemicolectomy owing to abscess formation around the cecum. A pathological
      analysis revealed diffuse intestinal ganglioneuromatosis in the cecum and colon.
      Colonoscopy performed eight months after hemicolectomy revealed multiple ulcers
      throughout the colon and rectum. The colorectal ulcers failed to respond to
      conservative treatment and ultimately required surgical resection. Diffuse
      ganglioneuromatosis was observed again in the resected specimen. This report
      illustrates a rare manifestation of diffuse intestinal ganglioneuromatosis in a
      patient with neurofibromatosis type 1.

PMID- 29021451
TI  - Otitis Media with ANCA-associated Vasculitis: A New Concept and the Associated
      Criteria.
AB  - A previously healthy 77-year-old Japanese man presented with a 2-week history of
      daily fevers peaking at 38 degrees C, chills, hearing loss, and almost 10 kg of
      unintentional weight loss over 2 months. Pure tone audiometry showed mixed
      conductive-sensorineural hearing loss: right, 63.6 dB, left, 80.0 dB. Blood tests
      after admission showed a high myeloperoxidase-antineutrophil cytoplasmic antibody
      (MPO-ANCA) level (>300 U/mL), so we suspected ANCA-related vasculitis. The
      Japanese Otorhinolaryngology Society has recently been advocating the concept of
      otitis media with ANCA-associated vasculitis (OMAAV). Our case met the criteria
      proposed, leading to our diagnosis.

PMID- 29021450
TI  - The Efficacy of a Genetic Analysis of the BMPR2 Gene in a Patient with Severe
      Pulmonary Arterial Hypertension and an Atrial Septal Defect Treated with
      Bilateral Lung Transplantation.
AB  - Severe pulmonary arterial hypertension (PAH) rarely develops in children with an
      atrial septal defect (ASD), even those with a large defect. We herein report the
      case of a 27-year-old man with a moderate-sized secundum ASD and right
      ventricular failure due to severe PAH, which developed in his early teens. He was
      diagnosed as having a genetic mutation of the bone morphogenetic protein receptor
      2 (BMPR2) gene and was successfully treated with bilateral lung transplantation
      with ASD path closure. In patients with congenital heart disease, a genetic
      analysis may provide information about the lifetime risk of developing PAH.

PMID- 29021452
TI  - Familial Adenomatous Polyposis with Multiple Helicobacter-negative Early Gastric
      Cancers Treated by Endoscopic Submucosal Dissection.
AB  - Stomach cancer rarely develops in patients with familial adenomatous polyposis
      (FAP), and Helicobacter pylori infection may increase the risk of FAP-related
      gastric cancer. We describe the case of a 64-year-old woman who developed
      multiple synchronous early gastric cancers without H. pylori infection. Nine
      cancer lesions were successfully treated by endoscopic submucosal dissection. An
      immunohistochemical analysis revealed that the tumors were positive for mucin
      (MUC)2, MUC6, and CDX2, but negative for MUC5AC, suggesting that the tumors were
      gastrointestinal mixed type. Periodical endoscopic surveillance is important for
      the detection of cancers at an early stage.

PMID- 29021453
TI  - Severe Alcoholic Hepatitis Effectively Treated with Vitamin E as an Add-on to
      Corticosteroids.
AB  - A 49-year-old woman with a history of heavy alcohol drinking was admitted to our
      hospital due to jaundice and abdominal distention. A blood test showed
      leukophilia, mild hypoalbuminemia, hyperbilirubinemia, hepatobiliary injury and
      coagulopathy. Image studies showed an extremely enlarged fatty liver and
      splenomegaly. The Japan alcoholic hepatitis score and Maddrey's discriminant
      function were 10 and 54 points, respectively. We diagnosed her with severe
      alcoholic hepatitis and treated her with corticosteroids, but her liver function
      did not improve. We therefore administered the vitamin E product tochopheryl
      acetate (150 mg/day) as an add-on therapy, after which her leukophilia, liver
      enzymes and coagulopathy improved immediately.

PMID- 29021454
TI  - Sudden Respiratory Failure due to Tracheobronchomalacia by Relapsing
      Polychondritis, Successfully Rescued by Multiple Metallic Stenting and
      Tracheostomy.
AB  - Relapsing polychondritis (RP) is a rare systemic autoimmune disease that affects
      cartilaginous structures. RP causes tracheobronchomalacia (TBM) by affecting the
      bronchial cartilage. TBM is a fatal condition characterized by excessive
      weakening of the walls of the trachea and bronchi. We herein report a case of a
      73-year-old man who experienced sudden respiratory failure due to TBM caused by
      RP. Immunosuppressive treatment did not improve his respiratory failure. Multiple
      metallic stentings dramatically improved his severe airway symptoms. When the
      airway condition becomes lethal in RP patients, then metallic stenting can be a
      useful treatment option.

PMID- 29021455
TI  - Enormous Ovarian Cyst.

PMID- 29021457
TI  - Progressive Constrictive Pericarditis Shortly after Purulent Pericarditis.

PMID- 29021456
TI  - Quantitative Assessment of Swallowing Dysfunction in Patients with Spinal and
      Bulbar Muscular Atrophy.
AB  - Objective This study aimed to evaluate swallowing dysfunction in patients with
      spinal and bulbar muscular atrophy and to identify the most appropriate method of
      assessing swallowing dysfunction using a videofluoroscopic swallowing study.
      Methods In the videofluoroscopic swallowing study, patients were instructed to
      swallow 3 mL of 40% weight/volume barium sulfate twice, and the pharyngeal
      residue was measured. We used three different methods to quantify the pharyngeal
      barium residue and an eight-point scale to evaluate the laryngeal penetration
      leading to aspiration pneumoniae. Patients We assessed 111 patients with spinal
      and bulbar muscular atrophy who weren't undergoing disease-specific treatment.
      Results Our results showed that the pharyngeal barium residue after initial
      swallowing correlated better with the bulbar-related functional rating scales
      than that after multiple deglutition. This correlation was vague when the data
      from patients whose barium residue was >50% were eliminated. In addition,
      evaluating the pharyngeal residue after initial swallowing proved to be the most
      sensitive method with regard to laryngeal penetration. Conclusion This study
      showed that the pharyngeal barium residue after initial swallowing was the most
      appropriate parameter for quantitatively assessing the degree of dysphagia using
      a videofluoroscopic swallowing study and suggests that this method may predict
      laryngeal penetration and aspiration in patients with spinal and bulbar muscular
      atrophy.

PMID- 29021458
TI  - Progressive Pseudolithiasis Associated with the Intravenous Administration of
      Ceftriaxone in Patients with Central Nervous System Infections.
AB  - We report four adult cases of ceftriaxone (CTRX)-induced pseudolithiasis and
      nephrolithiasis. With the exception of case 1, none of our cases showed abdominal
      symptoms. Our patients, who had central nervous system (CNS) infections, had been
      treated with CTRX (4 g/day) for 35-69 days. CTRX-induced pseudolithiasis and
      nephrolithiasis can appear depending on the total dose of CTRX and the duration
      for which it is administered. Patients with bacterial CNS infections who are
      treated with CTRX are typically treated with higher doses for longer periods. It
      should be recognized that these patients are at higher risk of developing CTRX
      induced pseudolithiasis and nephrolithiasis.

PMID- 29021459
TI  - Bilateral Frontal Lobe Vasogenic Edema Resulting from Hypertrophic
      Pachymeningitis due to Granulomatosis with Polyangiitis.
AB  - A 61-year-old woman presented with a 1-month history of decreased activities of
      daily living. Magnetic resonance imaging revealed abnormal intensities of the
      bilateral frontal lobes and enhancement of the thickened dura matter. A biopsy of
      the dura mater revealed multinucleated giant cells. She had sinusitis and
      hematuria; she was diagnosed with granulomatosis with polyangiitis. Hypertrophic
      pachymeningitis (HPM) was considered to have interrupted the venous flow and
      caused vasogenic edema. Bilateral frontal lobe edema resulting from HPM due to
      granulomatosis with polyangiitis has not been reported. A biopsy and examination
      for other organ complications were useful for the diagnosis and treatment of our
      patient.

PMID- 29021460
TI  - Dental Technicians' Pneumoconiosis.
AB  - A 40-year-old female dental technician visited our hospital for the investigation
      of a chest X-ray abnormality. Chest computed tomography demonstrated
      centrilobular nodules and lung volume reduction, and her serum KL-6 level was
      elevated. A histological analysis of the specimens obtained on a surgical lung
      biopsy showed peribronchiolar fibrosis with pigmented macrophages and cholesterol
      clefts. An energy-dispersive X-ray analysis showed that these lung tissues
      contained some metals, including indium. The serum indium level was also
      elevated. We diagnosed this patient with pneumoconiosis caused by exposure to
      sandblasting certain dental metals. This is the first reported case of
      pneumoconiosis in a dental technician associated with exposure to indium.

PMID- 29021462
TI  - Novel Imaging of Hypoglycemia-induced Myocardial Abnormality by Cardiac Magnetic
      Resonance T1-mapping.

PMID- 29021463
TI  - Uvula Hematoma.

PMID- 29021464
TI  - PR3-ANCA-positive Pulmonary Cryptococcosis.

PMID- 29021461
TI  - Isolation of ESBL-producing Bacteria from Sputum in Community-acquired Pneumonia
      or Healthcare-associated Pneumonia Does Not Indicate the Need for Antibiotics
      with Activity against This Class.
AB  - Objective In the past decade, extended-spectrum beta-lactamase (ESBL)-producing
      bacteria have increasingly frequently been isolated from various kinds of
      clinical specimens. However, the appropriate treatment of pneumonia in which ESBL
      producing bacteria are isolated from sputum culture is poorly understood. To
      investigate whether or not ESBL-producing bacteria isolated from sputum in
      pneumonia cases should be treated as the causative bacteria. Methods and Patients
      In this retrospective study, we screened for patients, admitted between January
      2009 and December 2015 in whom pneumonia was suspected and for whom sputum
      cultures yielded Escherichia coli or Klebsiella spp. isolates. We identified
      patients with community-acquired pneumonia (CAP) or healthcare-associated
      pneumonia (HCAP) from whom ESBL-producing bacteria had been isolated from sputum
      culture and to whom antibiotic treatment had been given with a diagnosis of
      pneumonia. We analyzed the patients' backgrounds and the effect of the antibiotic
      treatment for the initial 3-5 days. Results From 400 patients initially screened,
      27 with ESBL-producing bacteria were secondarily screened. In this subset of
      patients, 15 were diagnosed with pneumonia, including 7 with CAP (5 E. coli and 2
      K. pneumoniae) and 8 with HCAP (8 E. coli). These patients exhibited an average
      age of 84.1 years old, and 9 of 15 were men. No patients were initially treated
      with antimicrobials that are effective against isolated ESBL-producing bacteria.
      However, 13 of 15 patients showed improvement of pneumonia following the initial
      antibiotic treatment. Conclusion ESBL-producing bacteria isolated from sputum are
      not likely to be the actual causative organisms of pneumonia.

PMID- 29021465
TI  - Insulinoma with a History of Epilepsy: Still a Possible Misleading Factor in the
      Early Diagnosis of Insulinoma.
AB  - A delayed diagnosis of insulinoma remains a clinical issue. Hypoglycemic symptoms
      can mimic neuropsychiatric disorders such as epilepsy. A 27-year-old woman with a
      history of epilepsy and anti-epileptic drugs (AEDs) developed repeated seizures
      and neuropsychiatric symptoms after a 9-year asymptomatic interval. She had
      received transient treatment with AEDs before the possibility of hypoglycemia was
      considered. Following a clinical diagnosis of insulinoma, distal pancreatectomy
      was performed; her seizures didn't occur again. The early diagnosis of insulinoma
      requires vigilance not only for hypoglycemia in patients with neuropsychiatric
      symptoms but also for the possible masking effects of a history of epilepsy and
      preceding AED usage.

PMID- 29021466
TI  - Successful Treatment of a Case of Late-onset Colitis after Umbilical Cord
      Transplantation with Metronidazole: A Case Report and Literature Review.
AB  - Diarrhea after hematopoietic stem cell transplantation (HSCT) can be life
      threatening, and its etiology includes conditioning regimens, graft-versus-host
      disease (GVHD), infections, and transplantation-associated microangiopathy
      (iTAM). Cord colitis syndrome (CCS) has been described as a syndrome of culture
      negative and antibiotic-responsive persistent watery and non-bloody diarrhea of
      uncertain pathogenesis and occurs in umbilical cord blood transplantation (UCBT)
      recipients. We encountered a case similar to CCS that developed severe watery
      diarrhea after UCBT without any signs of GVHD or infection and responded well to
      metronidazole (MNZ) treatment. Since CCS is very rare, we herein describe a case
      of MNZ-effective diarrhea after UCBT.

PMID- 29021467
TI  - Tuberculosis of the Wrist Accompanied with Calcium Pyrophosphate.
AB  - This is a rare case of tuberculosis (TB) complicated with pseudogout of the wrist
      joint in a non-immunocompromised 84-year-old female with a history of pulmonary
      tuberculosis. She was diagnosed with extrapulmonary tuberculosis of the wrist
      based on a polymerase chain reaction (PCR) study and synovial fluid aspiration in
      which the cytology was positive for acid-fast bacilli. Calcium pyrophosphate was
      also positive. We must be careful not to miss articular tuberculosis as it may
      mimic common inflammatory arthritis, such as pseudogout of the wrist. Even if the
      patient is positive for calcium pyrophosphate, this does not exclude the
      possibility of articular tuberculosis.

PMID- 29021468
TI  - Esophageal Varix in an Adult Fontan Survivor.

PMID- 29021469
TI  - Elevation of Plasmin-alpha2-plasmin Inhibitor Complex Predicts the Diagnosis of
      Systemic AL Amyloidosis in Patients with Monoclonal Protein.
AB  - Objective The complication of systemic immunoglobulin light chain (AL)
      amyloidosis in patients with monoclonal immunoglobulin affects the prognosis, but
      amyloid deposition in tissues is sometimes difficult to detect due to bleeding
      tendencies and preferential distributions. However, fibrinolysis is known to be
      exacerbated in patients with systemic AL amyloidosis specifically. We therefore
      explored new biomarkers for predicting a diagnosis of systemic AL amyloidosis
      focusing on coagulation and fibrinolysis markers. Methods We reviewed the
      clinical features and treatment outcomes of patients with serum monoclonal
      protein, including primary systemic AL amyloidosis and multiple myeloma (MM),
      treated at our hospital between January 2008 and December 2014. Results Among
      several biomarkers, only the serum level of plasmin-alpha2-plasmin inhibitor
      complex (PIC) in patients with systemic AL amyloidosis (n=26) at the diagnosis
      was significantly higher than in patients with MM without AL amyloidosis (n=26)
      (mean+/-standard deviation, 3.69+/-2.82 MUg/mL vs. 1.23+/-0.97 MUg/mL, p<0.01).
      The cut-off for predicting a diagnosis of systemic AL amyloidosis in patients
      with serum monoclonal protein was 1.72 MUg/mL with 84.6% sensitivity and 80.8%
      specificity. Hepatic involvement resulted in a significantly higher PIC level
      than no involvement in patients with systemic AL amyloidosis. The serum PIC level
      was also associated with the hematological response of systemic AL amyloidosis.
      Conclusion PIC is a useful biomarker for the diagnosis and management of patients
      with systemic AL amyloidosis.

PMID- 29021470
TI  - EUS-guided Biliary Drainage for Malignant Perihilar Biliary Strictures after
      Further Transpapillary Intervention Has Been Judged to Be Impossible or
      Ineffective.
AB  - Objective Patients with perihilar malignancy often develop recurrence of
      infectious cholangitis, which makes further transpapillary intervention extremely
      difficult. As endoscopic ultrasound (EUS)-guided biliary drainage (EUS-BD) of an
      intrahepatic bile duct is a possible option for additional intervention, the aim
      of this study was to estimate the feasibility of such intervention. Methods and
      Patients Patients who had undergone EUS-BD after further transpapillary
      intervention was deemed impossible or ineffective were investigated in this
      study. Those who had not received previous interventions via the papilla were
      excluded. Procedure-related adverse events, clinical efficacy, and time to
      recurrence of jaundice or infectious cholangitis transthyretin (TTR) were
      evaluated. Results Seven patients were eligible for the study between 2007 and
      2016 (7 men; mean age, 77 years; 4 with perihilar cholangiocarcinoma and 3 with
      intrahepatic cholangiocarcinoma). No procedure-related adverse events were
      observed. EUS-BD was clinically effective and enabled hospital discharge in 4
      patients (57%). The TTR in these 4 clinically effective patients was 43, 105,
      118, and 147 days after the procedure (median, 112 days). Conclusion EUS-BD was
      found to be safe and often effective in patients in whom additional
      transpapillary intervention had become difficult, although its efficacy was
      limited to a short period.

PMID- 29021471
TI  - Syndrome of Inappropriate Antidiuretic Hormone Secretion in a Patient with Mucosa
      associated Lymphoid Tissue Lymphoma.
AB  - Syndrome of inappropriate antidiuretic hormone secretion (SIADH) may develop in
      association with several malignancies. However, as an immunohistochemical
      analysis is not performed in the majority cases, its true cause is often
      uncertain. We herein report a case of SIADH following chemotherapy due to tumor
      derived ADH production in a patient with mucosa-associated lymphoid tissue (MALT)
      lymphoma. A retrospective immunohistochemical analysis demonstrated ADH
      expression by lymphoma cells. These findings highlight the importance of using an
      immunohistochemical analysis to determine ADH production by tumor cells in
      patients with SIADH. Such analyses play an important role in elucidating the
      pathogenesis of SIADH and determining the most appropriate treatment.

PMID- 29021472
TI  - Pneumothorax Secondary to Septic Pulmonary Emboli in a Long-term Hemodialysis
      Patient with Psoas Abscess.
AB  - Pneumothorax secondary to septic pulmonary embolism (SPE) is rare but life
      threatening. We herein report a long-term hemodialysis patient with psoas abscess
      caused by methicillin-resistant Staphylococcus aureus, associated with other
      muscle and splenic abscesses and SPE. Intravenous vancomycin treatment and
      percutaneous drainage of the psoas abscess rapidly improved her condition.
      However, the SPE lesions continued to increase, and right-sided pneumothorax
      occurred 10 days after treatment. The pneumothorax resolved after two months and
      SPE and all abscesses after four months of treatment. Since late-onset
      pneumothorax caused by SPE can occur despite successful treatment of the primary
      infection, care should be taken with such patients.

PMID- 29021474
TI  - Heteroplasmy of the m.3243A>G Mutation May Influence Phenotypic Heterogeneity.

PMID- 29021473
TI  - Oncocytic Type Intraductal Papillary Mucinous Neoplasm of the Pancreas with
      Unusually Low Mucin Production Mimicking Intraductal Tubulopapillary Neoplasm: A
      Report of a Case Diagnosed by a Preoperative Endoscopic Biopsy.
AB  - We herein report the case of a 78-year-old woman with an intraductal tumor with
      scant mucin production in a moderately dilated main pancreatic duct that
      resembled an intraductal tubulopapillary neoplasm (ITPN) on imaging. An
      endoscopic transpapillary forceps biopsy enabled an accurate preoperative
      diagnosis of the tumor as an oncocytic type intraductal papillary mucinous
      neoplasm (IPMN) of the pancreas microscopically showing papillary growth
      consisting of oncocytic cells with a typical mucin expression profile, although
      with few intraepithelial lumina containing mucin. This is the first case of an
      oncocytic type IPMN mimicking an ITPN that was able to be diagnosed
      preoperatively.

PMID- 29021475
TI  - Successful Pulmonary Artery Embolization for the Management of Hemoptysis in a
      Patient with Eisenmenger Syndrome Caused by Patent Ductus Arteriosus.
AB  - The patient was a 19-year-old woman who was diagnosed with patent ductus
      arteriosus complicating Eisenmenger syndrome at a previous medical institution.
      She was referred to our hospital and arranged for lung transplantation. She
      developed hemoptysis after the introduction of i.v. epoprostenol, which was
      administered as a bridging treatment while the patient awaited lung
      transplantation. She continued to suffer from recurrent hemoptysis, even after
      switching from i.v. epoprostenol to i.v. treprostinil. Angiography of the
      systemic and pulmonary arteries revealed the vessel responsible for the recurrent
      hemoptysis and pulmonary artery embolization was successfully performed. It is
      essential to identify the culprit vessel and physicians must not hesitate in
      performing embolization when patients develop lethal hemoptysis.

PMID- 29021476
TI  - A Rare Monocytic Crisis of Chronic Myelogenous Leukemia Presenting with Unusual
      Extramedullary Manifestations and an Atypical (14;22)(q24;q11.2) Translocation in
      the Bone Marrow.
AB  - A 48-year-old man was admitted due to marked leukocytosis. Bone marrow
      examinations resulted in a diagnosis of Philadelphia (Ph) chromosome-positive
      chronic myeloid leukemia. One month later, massive muscle and bone invasion by
      leukemic cells was detected. After induction chemotherapy, he complained of a
      headache and visual loss, which was caused by a leukemic infiltration in the
      central nervous system. After temporary remission in response to chemotherapy,
      the disease relapsed in the form of an intracranial tumor. The unusual
      t(14;22)(q24;q11.2) translocation of the Ph-chromosome and the significant
      increase in monocytes observed might have contributed to the unique and
      aggressive clinical course.

PMID- 29021477
TI  - Management of Osteoporosis in Chronic Kidney Disease.
AB  - Chronic kidney disease (CKD) patients with coexisting osteoporosis are becoming
      common. Many of the therapeutic agents used to treat osteoporosis are known to be
      affected by the renal function. It is generally thought that osteoporosis in G1
      to G3 CKD patients can be treated as in non-CKD patients with osteoporosis. In
      stage 4 or more advanced CKD patients and CKD patients on dialysis with
      osteoporosis, however, bisphosphonates must be used with caution, bearing in mind
      the potential development of such disorders as adynamic bone disease. The use of
      vitamin D preparations in low doses is relatively safe. In postmenopausal women,
      raloxifene must be administered with caution. When using denosumab, the serum
      calcium concentrations should be monitored carefully to prevent the development
      of hypocalcemia, and active vitamin D preparations should be administered
      concomitantly. The present article provides an overview of the management of
      osteoporosis in CKD patients.

PMID- 29021478
TI  - Rhabdomyolysis in a Patient with Polyarteritis Nodosa.
AB  - Polyarteritis nodosa (PAN) is a medium vessel vasculitis affecting systemic
      organs. Muscle involvement of PAN usually lacks elevation of creatinine kinase
      (CK). We herein report a case of PAN with rhabdomyolysis. A 71-year-old man was
      hospitalized because of muscle weakness of the lower limbs that persisted for 1
      month. On a physical examination, rapidly progressive lower proximal muscle
      weakness and bilateral drop foot were observed. His blood test showed an
      elevation in the C-reactive protein (19.5 mg/dL) and CK (13,435 IU/L) levels and
      negativity for anti-neutrophilic cytoplasmic antibody. Computed tomographic
      angiography showed stenosis of the left renal artery. Electromyogram indicated
      mono-neuritis multiplex pattern, and enhanced magnetic resonance imaging
      demonstrated discretely granular hyperintensities on T2 and slow tau inversion
      recovery in his femoral muscles. A femoral muscle-biopsy specimen showed
      fibrinoid necrosis of medium-sized vessels and disruption of the elastic lamina
      of the vessel wall in fascia. Furthermore, muscle necrosis was localized
      depending on the arterial distribution, suggesting ischemic changes in the
      muscles. Given these findings, he was diagnosed with PAN with rhabdomyolysis and
      treated with methyl-prednisolone pulse therapy followed by oral prednisolone at
      50 mg/day. He was additionally treated with monthly intravenous cyclophosphamide
      at 500 mg. Sustained remission has been obtained for two months since the
      treatment. Although rhabdomyolysis rarely manifests with PAN, it should be
      included in a differential diagnosis of febrile patients presenting with acute
      myalgia and weakness with CK elevation.

PMID- 29021479
TI  - A Japanese Case of Esophageal Lichen Planus that Was Successfully Treated with
      Systemic Corticosteroids.
AB  - Esophageal lichen planus (ELP) is rare and only about 80 cases have been reported
      in the literature. An 85-year-old woman presented with dysphagia and odynophagia.
      Endoscopy revealed a severe stricture in the proximal esophagus. Oral
      examinations at two years after the first endoscopy revealed erosions around the
      gingiva, and an examination of biopsy specimens taken from the site of erosion
      led to a diagnosis of oral lichen planus. Esophageal endoscopy was performed
      again, and biopsy specimens showed spongiosis and necrotic keratinocytes in the
      epithelium (civatte bodies). The patient was diagnosed with ELP and was treated
      with systemic corticosteroids, which resulted in clinical relief.

PMID- 29021480
TI  - The Effects of Mitiglinide and Repaglinide on Postprandial Hyperglycemia in
      Patients Undergoing Methylprednisolone Pulse Therapy.
AB  - One adverse effect of methylprednisolone (MP) pulse therapy is an acute dose
      dependent increase in the blood glucose level. Five patients with thyroid
      ophthalmopathy but normal glucose tolerance received MP pulse therapy (3 cycles,
      3 days/week) and were assessed by continuous glucose monitoring. Steroid therapy
      increased the mean sensor glucose level, and all patients developed steroid
      induced diabetes. The patients were treated alternately with mitiglinide (30
      mg/day) and repaglinide (1.5 mg/day) during the second or third MP pulse therapy.
      The sensor glucose levels before lunch and dinner were more favorable during
      treatment with repaglinide than during treatment with mitiglinide. Repaglinide
      may be more clinically appropriate than mitiglinide.

PMID- 29021483
TI  - Transarterial Embolization of a Ruptured Renal Angiomyolipoma.

PMID- 29021481
TI  - Cryptococcal Pleuritis Presenting with Lymphocyte-predominant and High Levels of
      Adenosine Deaminase in Pleural Effusions Coincident with Pulmonary Tuberculosis.
AB  - Co-infection with cryptococcus and tuberculosis has rarely been reported. We
      herein report a case of an 80-year-old man with cryptococcal pleuritis concurrent
      with pulmonary tuberculosis. He was admitted for progression of left pleural
      effusion and consolidation in the left upper lobe. Culture for Mycobacterium
      tuberculosis was positive in sputum, and analyses of pleural effusion revealed
      lymphocyte-predominant high levels of adenosine deaminase (ADA). Medical
      thoracoscopy revealed massive infiltration of Cryptococcus neoformans in pleura
      without granuloma. This is the first case report of cryptococcal pleuritis
      coincident with pulmonary tuberculosis. Cryptococcal pleuritis should be ruled
      out when the adenosine deaminase levels are elevated in pleural effusion.

PMID- 29021482
TI  - Disseminated Cryptococcosis with Marked Eosinophilia in a Postpartum Woman.
AB  - Disseminated cryptococcosis usually develops in immunosuppressed patients. A 33
      year-old postpartum woman developed disseminated cryptococcosis with marked
      eosinophilia. She presented with a cough and a week-long fever. A computed
      tomography scan showed multiple pulmonary nodules randomly distributed.
      Eosinophils were observed to have increased in number in both her peripheral
      blood and bronchoalveolar lavage fluid. A transbronchial lung biopsy and
      cerebrospinal fluid specimens revealed findings consistent with cryptococcal
      infection. Disseminated cryptococcosis can present with marked eosinophilia of
      the peripheral blood and lung tissues. Additionally, the postpartum immune status
      may sometimes be involved in the development of opportunistic infections in
      previously healthy women.

PMID- 29021484
TI  - Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis Complicated by
      Periaortitis and Cranial Hypertrophic Pachymeningitis: A Report of an Autopsy
      Case.
AB  - Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic
      inflammatory disorder categorized as small-vessel vasculitis. We herein report an
      elderly Japanese man with AAV (granulomatosis with polyangiitis affecting the
      eyes, nose, lungs, and kidneys) who also showed periaortitis at the diagnosis and
      developed cranial hypertrophic pachymeningitis (HP) during steroid maintenance
      therapy. His consciousness disturbance caused by HP improved after steroid pulse
      therapy, but he died of aspiration pneumonia. Autopsy findings showed giant cells
      in the thickened pachymeninges and obsolete inflammatory lesions in the aortic
      adventitia and renal tubulointerstitium. This is the first case of AAV
      complicated by periaortitis and cranial HP.

PMID- 29021485
TI  - Spontaneous Regression of Epithelioid Angiosarcoma in a Young Woman.
AB  - A 20-year-old Japanese woman with a history of pulmonary atresia was referred to
      our hospital after the detection of an abnormal mass in the right lung and
      mediastinal lymphadenopathy. A cytological specimen obtained by transbronchial
      brushing indicated that the pathological diagnosis was non-small cell lung
      cancer. During the follow-up period, the tumor spontaneously regressed. At four
      months after the diagnosis, she experienced sudden bleeding from the small
      intestine. The histological characteristics of the small intestine tumor were
      compatible with the cytological characteristics of the lung tumor. Detailed
      immunohistochemical analyses led to a final diagnosis of epithelial angiosarcoma
      of the small intestine, which might have formed metastatic lesions in the lung.

PMID- 29021486
TI  - A Hypoglycemia-inducing Giant Borderline Phyllodes Tumor Secreting High-molecular
      weight Insulin-Like Growth Factor II: Immunohistochemistry and a Western Blot
      Analysis.
AB  - A 50-year-old woman with a large right breast mass was emergently hospitalized
      for generalized weakness and fatigue. A histological examination of tumor biopsy
      specimens revealed a phyllodes tumor (PT). She suddenly lost consciousness due to
      severe hypoglycemia. Non-islet cell tumor hypoglycemia (NICTH) due to the PT was
      suspected. The tumor was emergently resected. A histological examination revealed
      a borderline PT. The patient recovered from the hypoglycemic episode. High
      molecular-weight insulin-like growth factor II was detected in serum that had
      been collected preoperatively and in the tumor tissue, but not in serum that had
      been collected postoperatively. We herein present a case of a borderline PT with
      NICTH.

PMID- 29021488
TI  - Aerobic Dechlorination of Dichloromethane Using Biostimulation Agent BD-C in
      Continuous and Batch Cultures of Xanthobacter autotrophicus GJ10.
AB  - It is important to construct microbiological treatment systems for organic
      solvent-contaminated water. We developed a continuous culture supplemented with a
      biostimulation agent named BD-C, which is formulated from canola oil, and
      Xanthobacter autotrophicus strain GJ10 for an aerobic dichloromethane (DCM)
      dechlorinating microorganism. The continuous culture was a chemostat constructed
      using a 1 L screw-capped bottle containing artificial wastewater medium with 2.0
      mM DCM and 1.0% (v/v) BD-C. The expression of genes for DCM metabolism in the
      dechlorinating aerobe was monitored and analyzed by reverse transcription
      quantitative PCR. Strain GJ10 was able to dechlorinate approximately 74% of the
      DCM in medium supplemented with BD-C during 12 days of incubation. The DCM
      dechlorination rate was calculated to be 0.11 mM/day. The DeltaDeltaCT method
      showed that expression of haloalkane dehalogenase increased 5.4 times in the
      presence of BD-C. Based on batch culture growth tests conducted with mineral salt
      medium containing three DCM concentrations (0.07, 0.20, 0.43 and 0.65 mM) with BD
      C, the apparent maximum specific consumption rate (numax) and the saturation
      constant (Ks) determined for DCM degradation in this test were 19.0 nmol/h/CFU
      and 0.44 mM, respectively. In conclusion, BD-C enhanced the aerobic degradation
      of DCM by strain GJ10.

PMID- 29021487
TI  - Severe Infection of Pseudomonas aeruginosa during Eculizumab Therapy for
      Paroxysmal Nocturnal Hemoglobinuria.
AB  - Eculizumab is the complement inhibitor administered to ameliorate intravascular
      hemolysis in paroxysmal nocturnal hemoglobinuria. Whether or not the inhibitory
      mechanism may also increase the susceptibility to non-Neisserial infection is
      unclear. A 73-year old woman presented with bacteremia, cholecystitis and liver
      abscess with Pseudomonas aeruginosa. Although she had been neutropenic for 21
      years, she had no history of severe infection before eculizumab had been
      administered. The infection with P. aeruginosa was successfully controlled with
      antibiotics, granulocyte colony-stimulating factor and cholecystectomy. The
      present case might be representative of less common bacterial infections than
      Neisseria spp. among patients treated with eculizumab.

PMID- 29021489
TI  - Surface Morphology of Cosmetic Film Consisting of PEG-Diisostearate Amphiphilic
      Random Copolymer, Xanthan Gum, and Solvents.
AB  - The surface morphology of a cosmetic film consisting of an amphiphilic random
      copolymer (methoxy polyethylene glycol-23 methacrylate/glyceryl diisostearate
      methacrylate copolymer, MPM-GDM) and solvents has been studied. The cosmetic film
      was prepared through the evaporation of water from a homogeneous aqueous mixture
      of MPM-GDM, xanthan gum, and solvents. MPM-GDM was soluble in water, monohydric
      alcohols, and 1,3-butylene glycol (1,3-BG), whereas it hardly dissolved in
      glycerin. The surface morphology was examined by changing the solvent composition
      of 1,3-BG (good solvent) and glycerin (poor solvent). Confocal laser scanning
      microscopy (CLSM) images of the cosmetic film showed that MPM-GDM spread through
      the whole film in the absence of glycerin, whereas the addition of glycerin led
      to the formation of a sea-island structure. It was assumed that the size of the
      MPM-GDM domain was determined by the balance between two factors: the miscibility
      (or the interfacial tension) of MPM-GDM against the solvents and the viscosity of
      the continuous phase. We also demonstrated that the concentration of both MPM-GDM
      and xanthan gum affected the surface morphology. Control of the surface
      morphology by changing the solubility of MPM-GDM is expected to be useful for
      improving the functionality and feel of cosmetic films.

PMID- 29021491
TI  - Effects of Sterol-Like Additives on Phase Transition Behavior of Ion-Pair
      Amphiphile Bilayers.
AB  - The incorporation of additive in lipid bilayers is one of the ordinary approaches
      for modulating their properties. Additive effect on phase transition of ion-pair
      amphiphile (IPA) bilayers, however, is not known. In this work, four double
      chained IPAs with different hydrocarbon chain lengths and symmetry were designed
      and synthesized from single-chained cationic and anionic surfactants by the
      precipitation method. By using differential scanning calorimetry (DSC), the
      thermotropic transition behavior from gel phase (Lbeta) through rippled phase
      (Pbeta') if any to liquid-crystalline phase (Lalpha) was studied for bilayers of
      these lipid-like IPAs in excess water. The effects of three sterol-like additives
      (cholesterol, alpha-tocopherol, and alpha-tocopheryl acetate) in IPA bilayers on
      thermal phase behavior were then systematically investigated. The experimental
      results revealed that with increasing concentration of additive, the phase
      transition temperatures were unaffected on the one hand and the enthalpies of
      phase transition were decreased on the other hand. When the addition of additive
      exceeded a specific amount, the phase transition disappeared. More hasty
      disappearance of phase transition was found for IPAs with lower total number of
      carbon atoms in the hydrocarbon chains. For IPAs with the same total number of
      carbon atoms in the hydrocarbon chains, the disappearance of phase transition is
      more hasty for the asymmetric one than for the symmetric one. Similar effects on
      thermal phase behavior of four IPA bilayers were exhibited by the three additives
      with similar chemical structures. Possible mechanism of additive effects on phase
      transition of IPA bilayers was then proposed in line with that of lipid bilayers.

PMID- 29021490
TI  - Synthesis and Application of a New Amphiphilic Antioxidant.
AB  - A new amphiphilic antioxidant (tannyl stearate) derived from reaction of tannic
      acid with stearic acid was synthesized in order to improve tannic acid solubility
      in lipid materials. This reaction gives many products having different degree of
      esterification (tannyl mono, di, tri, tetra, penta, hexa, hepta......stearate)
      which were separated using silica gel column chromatography and tentative
      identification was carried out using thin layer chromatography (TLC). The
      intrinsic viscosities (eta) were used to differentiate between the different
      molecular weight of the produced esters1). Tannyl penta stearate is assumed to be
      the most suitable amphiphilic antioxidant derivative, where those derivatives
      with less degree of esterification would be less soluble in fat, and those of
      higher degree of esterification would exhaust more hydroxyl group that cause
      decreases of antioxidant activity. The structure of tannyl penta stearate was
      approved depending on its chemical analysis and spectral data (IR, H1 NMR,). The
      emulsification power of tannyl penta stearate was then determined according to
      method described by El-Sukkary et al.2), in order to prove its amphiphilic
      property. Then tannyl penta stearate was tested for its antioxidant and radical
      scavenging activities in three different manners, those are, lipid oxidation in
      sunflower oil using Rancimat, (DPPH) free radical scavenging and total
      antioxidant activity. {Pure tannic acid (T), butylhydroxyanisol (BHA) and
      butylhydroxytoluene (BHT) were used as reference antioxidant radical saving
      compounds}. Then tannyl penta stearate was added to sunflower oil, frying process
      was carried out and all physicochemical parameters of the oil were considered,
      and compared to other reference antioxidant in order to study the effect of this
      new antioxidant toward oil stability. Acute oral toxicity of the tannyl penta
      stearate was carried out using albino mice of 21-25 g body weight to determine
      its safety according to the method described by Goodman et al.3). Also liver and
      kidney functions of those mice were checked. Thus it could be concluded that the
      addition of tannyl penta stearate to frying oils offers a good protection against
      oxidation. The effectiveness of tannyl penta stearate as lipid antioxidant has
      been attributed mainly to its stability at high temperature. And according to
      acute lethal toxicity test tannyl penta stearate was found to be a safe compound
      that can be used as food additive.

PMID- 29021492
TI  - Optimization of the Synthesis of Structured Phosphatidylcholine with Medium Chain
      Fatty Acid.
AB  - Structured phosphatidylcholine was successfully produced by acidolysis between
      phosphatidylcholine and free medium chain fatty acid, using phospholipase A1
      immobilized on Duolite A568. Response surface methodology was applied to optimize
      the reaction system using three process parameters: molar ratio of substrates
      (phosphatidylcholine to free medium chain fatty acid), enzyme loading, and
      reaction temperature. All parameters evaluated showed linear and quadratic
      significant effects on the production of modified phosphatidylcholine; molar
      ratio of substrates contributed positively, but temperature influenced
      negatively. Increased enzyme loading also led to increased production of modified
      phosphatidylcholine but only during the first 9 hours of the acidolysis reaction.
      Optimal conditions obtained from the model were a ratio of phosphatidylcholine to
      free medium chain fatty acid of 1:15, an enzyme loading of 12%, and a temperature
      of 45 degrees C. Under these conditions a production of modified
      phosphatidylcholine of 52.98 % were obtained after 24 h of reaction. The
      prediction was confirmed from the verification experiments; the production of
      modified phosphatidylcholine was 53.02%, the total yield of phosphatidylcholine
      64.28% and the molar incorporation of medium chain fatty acid was 42.31%. The
      acidolysis reaction was scaled-up in a batch reactor with a similar production of
      modified phosphatidylcholine, total yield of phosphatidylcholine and molar
      incorporation of medium chain fatty acid. Purification by column chromatography
      of the structured phosphatidylcholine yielded 62.53% of phosphatidylcholine
      enriched with 42.52% of medium chain fatty acid.

PMID- 29021493
TI  - Lyoprotective Effect of Alkyl Sulfobetaines for Freeze-drying 1,2-Dipalmitoyl-sn
      glycero-3-phosphocholine Liposomes.
AB  - A liposome is a molecular assembly in the form of a vesicle comprised of a
      phospholipid bilayer. Liposomes can be used as molecular containers in various
      fields such as pharmaceutical, cosmetic, and food industries. It is difficult to
      maintain the original structure of liposomes in an aqueous medium. Phospholipids,
      which are components of liposomes, are susceptible to hydrolysis, which causes
      disruption of the liposomal structure and dysfunction of the molecular container.
      In this context, freeze-drying liposomes is a preferable method to improve the
      shelf life of liposomes. However, when freeze-drying liposomes, a lyoprotective
      agent is required to preserve their original structure. In this study, we
      investigate whether alkyl sulfobetaines (SBn, n: number of carbons in the alkyl
      chain, n = 1-18) can be used as lyoprotectants for 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine (DPPC) liposomes. The results indicated that the length of the
      alkyl chain of the SBn was an important factor to prevent liposome disruption
      during the freeze-drying and subsequent rehydration processes. The use of SBn
      with an alkyl chain of intermediate length (n = 6-10) could prevent liposome
      disruption and remarkably reduce the gel-to-liquid crystal phase transition
      temperature (Tm) of the freeze-dried liposomes. This indicates that these SBn
      could intercalate in the dried bilayer and reduce intermolecular interaction
      between DPPC in the bilayer. The Tm reduction of the freeze-dried liposomes
      should contribute to prevention of the gel-to-liquid phase transition of the
      liposomes during the rehydration process, which has been known to be a main cause
      of liposome disruption. We expect that the results from this study will provide
      an insight into the influence of zwitterionic additives on freeze-dried lipid
      bilayers and the lyoprotective effect, which should be useful in many biochemical
      and biomedical fields.

PMID- 29021494
TI  - Analysis of Lutein in Mugwort (Artemisia princeps Pamp.) Paste and Evaluation of
      Manufacturing Processes.
AB  - Lutein, a type of xanthophyll, possesses antioxidative properties that contribute
      to the prevention of various diseases. Preliminary screening has shown that
      Japanese mugwort (Artemisia princeps Pamp.) contains high amounts of lutein. In
      this study, we evaluated the lutein concentration in a processed mugwort product
      (mugwort paste). By using high-performance liquid chromatography coupled with
      visible light detection or mass spectrometry, the lutein concentration in mugwort
      paste was determined as 38 mg/100 g dry weight, which indicates that mugwort is a
      potentially valuable natural food source of lutein. We also investigated the
      effects of the manufacturing process and found that the lutein content was
      significantly increased by the boiling and dehydrating processes during the
      production of mugwort paste. Mugwort paste that is rich in lutein may therefore
      serve as an effective nutraceutical.

PMID- 29021495
TI  - Structure of the Microemulsion of Polyglycerol Polyricinoleate Encapsulating
      Vitamin E.
AB  - The structures of micelles and microemulsions consisting of polyglycerol
      polyricinoleate (PGPR) were investigated by small-angle X-ray scattering (SAXS)
      and rheological measurements. The SAXS results show that amphiphilic PGPR
      molecules form stable micelles in glycerol. When vitamin E is added to the PGPR
      micelles, it is encapsulated in the micelles and forms an emulsion. These
      micelles are stable towards mechanical shearing up to a shear rate of 1000 s-1,
      with shear thinning occurring in the emulsion above 100 s-1, indicating that the
      emulsion may undergo break up by shearing, but recovers the structure by
      releasing shear strain.

PMID- 29021496
TI  - Comparison of the Distribution of Unsaturated Fatty Acids at the Sn-2 Position of
      Phospholipids and Triacylglycerols in Marine Fishes and Mammals.
AB  - Highly unsaturated fatty acid (HUFA) binding at the sn-2 position of
      phospholipids (PL) becomes a resource for prostaglandin, leukotriene, resolvin,
      and protectin synthesis. Both triacylglycerol (TAG) and PL synthesis pathways in
      vivo are via phosphatidic acid; therefore, the distribution of fatty acid species
      at the sn-2 position must theoretically be the same for TAG and PL if
      rearrangement does not occur. However, it is known that little HUFA is located at
      the sn-2 position of TAG in marine mammals. Therefore, distribution of fatty acid
      species at the sn-2 position of TAG and PL was compared between marine fishes and
      mammals in this study. The composition of fatty acids binding at the sn-2 or sn
      1,3 position of PL and TAG was analyzed via hydrolysis with enzymes and GC-FID.
      The results showed that 20:4n-6, 20:5n-3, 22:5n-3, and 22:6n-3 were primarily
      located at the sn-1,3 positions of TAG in marine mammals. Comparison of the
      binding positions of HUFA and 16:0 in PL and TAG suggested the existence of
      Lands' cycle in marine fishes and mammals. In conclusion, both marine fishes and
      mammals condensed HUFA as a source of eicosanoid at the sn-2 position of PL.
      Furthermore, abundance ratios for 22:5n-3 or 22:6n-3 at the sn-2 position (sn-2
      ratio) in TAG and PL (calculated by the equation: [abundance ratio at sn-2
      position of TAG]/[abundance ratio at sn-2 position of PL]) was less than 0.35 in
      marine mammals; however, it was greater than 0.80 in marine fishes. These
      differences suggested that the HUFA consisted of 22 carbon atoms and had
      different roles in marine fishes and mammals.

PMID- 29021497
TI  - Comparison of Essential Oils from Three Kinds of Cryptotaenia japonica Hassk
      (Kirimitsuba, Nemitsuba, and Itomitsuba) used in Japanese Food.
AB  - The compositions of the essential oils from three kinds of Cryptotaenia japonica
      Hassk ("Mitsuba" in Japanese, Kirimitsuba (KM), Nemitsuba (NM), and Itomitsuba
      (IM)) were investigated by capillary GC/GC-MS. The oils contained 53 volatile
      components, of which 95% were terpenoids. The major constituents were
      sesquiterpenoids, which were alpha-selinene (KM: 39.1%; NM: 38.4%; IM: 13.2%),
      beta-selinene (15.5%, 15.2%, 4.8%), germacrene D (12.1%, 7.2%, 24.1%), trans
      farnesene (11.1%, 6.0%, 10.9%), beta-elemene (2.9%, 2.9%, 6.8%), and trans
      caryophyllene (1.7%, 1.7%, 2.6%). The main sesquiterpene found in KM and NM was
      alpha-selinene and in IM was germacrene D. The major monoterpenes found were beta
      myrcene (3.8%, 6.7%, and 3.5%) and beta-pinene (2.8%, 0.2%, and 1.4%).

PMID- 29021498
TI  - Chinese Journal of Nuclear Medicine and Molecular Imaging Volume 37, Number 9,
      September 25, 2017.

PMID- 29021499
TI  - Chitosan-Acrylic Polymeric Nanoparticles with Dynamic Covalent Bonds. Synthesis
      and Stimuli Behavior.
AB  - Drug delivery represents one of the most important research fields within the
      pharmaceutical industry. Different strategies are reported every day in a dynamic
      search for carriers with the ability to transport drugs across the body, avoiding
      or decreasing toxic issues and improving therapeutic activity. One of the most
      interesting strategies currently under research is the development of drug
      delivery systems sensitive to different stimuli, due to the high potential
      attributed to the selective delivery of the payload. In this work, a stimuli
      sensitive nanocarrier was built with a bifunctional acrylic polymer, linked by
      imine and disulfide bonds to thiolate chitosan, the latter being a biopolymer
      widely known in the field of tissue engineering and drug delivery by its
      biodegradability and biocompatibility. These polymer nanoparticles were exposed
      to different changes in pH and redox potential, which are environments commonly
      found inside cancer cells. The results proof the ability of the nanoparticles to
      keep the original structure when either changes in pH or redox potential were
      applied individually. However, when both stimuli were applied simultaneously, a
      disassembly of the nanoparticles was evident. These special characteristics make
      these nanoparticles suitable nanocarriers with potential for the selective
      delivery of anticancer drugs.

PMID- 29021501
TI  - Early small bowel perforation due to aflibercept.
AB  - In patients with malignancy who receive aflibercept based chemotherapy,
      gastrointestinal perforation is among the reported adverse events with a
      prevalence of 1.9%. This complication may lead to mortality up to 10.8%. We here
      report a case of small bowel perforation that occurred fifteen days after the
      first cycle of aflibercept in a 58-year old female who had metachronous
      colorectal liver metastases. Emergency laparotomy was performed and revealed a
      small bowel perforation without any anastomotic dehiscence. Surgery was followed
      by uneventful outcome. The use of aflibercept in patients with malignancy may be
      associated with very early gastrointestinal perforation and this should be known
      by oncologist and surgeons.

PMID- 29021500
TI  - Optimum culture duration for growing oocytes to attain meiotic and fertilization
      competence.
AB  - To determine the optimum culture duration for porcine growing oocytes (GOs) to
      attain maturation competence, we examined the meiotic competence, chromatin
      configuration, and fertilization ability of porcine oocytes obtained from early
      antral follicles and cultured for 10-16 days. The survival rate of oocytes after
      10 days of culture (62.8%) was similar to that of oocytes after 12 days of
      culture (55%) and significantly higher than that of oocytes cultured for 14 and
      16 days (52.9 and 24.3%, respectively). No significant difference was observed in
      the diameter of ooplasm from oocytes cultured for different durations (117.4
      118.3 MUm). The maturation rates of surviving oocytes after 10 and 16 days of
      culture (38.3 and 22.7%, respectively) were significantly lower than those of
      oocytes cultured for 12 and 14 days, and their in vivo counterparts (52.8-62.4%).
      The number of oocytes with surrounded-nucleolus chromatin was significantly lower
      in the 10-day culture group (78.4%) as compared with 14-day culture and in vivo
      counterpart groups (93.6 and 95.1%, respectively). After in vitro maturation and
      intracytoplasmic sperm injection, no significant difference was observed in the
      rate of fertilization among oocytes cultured for 12 and 14 days, and their in
      vivo counterparts (40.5-47.2%). Thus, porcine GOs required at least 12 days to
      acquire meiotic and fertilization competence, and the culture duration to
      maximize the number of mature oocytes ranged from 12 to 14 days.

PMID- 29021502
TI  - Structural analysis of an innate immunostimulant from broccoli, Brassica oleracea
      var. italica.
AB  - Vegetables are eaten as part of a healthy diet throughout the world, and some are
      also applied topically as a traditional medicine. We evaluated the innate
      immunostimulating activities of hot water extracts of various vegetables using
      the silkworm muscle contraction assay system, and found that broccoli, Brassica
      oleracea var. italica, contains a strong innate immunostimulant. We purified the
      innate immunostimulant from broccoli, and characterized the chemical structure by
      chemical analyses and NMR spectroscopy. The innate immunostimulant comprised
      galacturonic acid, galactose, glucose, arabinose, and rhamnose, and had a pectic
      like polysaccharide structure. To determine the structural motif involved in the
      innate immunostimulating activity, we modified the structure by chemical and
      enzymatic treatment, and found that the activity was attenuated by pectinase
      digestion. These findings suggest that a pectic-like polysaccharide purified from
      broccoli has innate immune-stimulating activity, for which the polygalacturonic
      acid structure is necessary.

PMID- 29021503
TI  - Characterization of the chemical structure and innate immune-stimulating activity
      of an extracellular polysaccharide from Rhizobium sp. strain M2 screened using a
      silkworm muscle contraction assay.
AB  - We screened innate immunostimulant-producing bacteria using a silkworm muscle
      contraction assay, and isolated Rhizobium sp. strain M2 from soil. We purified
      the innate immunostimulant from strain M2, and characterized the chemical
      structure by nuclear magnetic resonance spectroscopy and chemical analyses. The
      innate immunostimulant (M2 EPS) comprised glucose, galactose, pyruvic acid, and
      succinic acid with a molar ratio of 6.8:1.0:0.9:0.4, and had a succinoglycan-like
      high molecular-weight heteropolysaccharide structure. To determine the structural
      motif involved in the innate immunostimulating activity, we modified the M2 EPS
      structure chemically, and found that the activity was increased by removal of the
      succinic and pyruvic acid substitutions. Strong acid hydrolysis completely
      inactivated the M2 EPS. Unmasking of the beta-1,3/6-glucan structure of the side
      chain by deacylation and depyruvylation may enhance the innate immune-stimulating
      activity of M2 EPS. These findings suggest that the succinoglycan-like
      polysaccharide purified from strain M2 has innate immune-stimulating activity,
      and its glycan structure is necessary for the activity.

PMID- 29021504
TI  - Ethanol extracts of Aster yomena (Kitam.) Honda inhibit adipogenesis through the
      activation of the AMPK signaling pathway in 3T3-L1 preadipocytes.
AB  - The leaves of Aster yomena (Kitam.) Honda have long been used as a traditional
      herb for treating disorders including coughs, asthma, and insect bites. According
      to recent studies, A. yomena leaf extracts have several pharmacological
      properties, including anti-inflammatory, antioxidant, and anti-asthmatic
      activities. However, little information is available regarding their anti-obesity
      effect. In this study, we investigated the inhibitory effect of the ethanol
      extracts of A. yomena leaves (EEAY) on adipocyte differentiation and adipogenesis
      using 3T3-L1 preadipocytes. When 3T3-L1 preadipocytes were treated with various
      concentrations of EEAY (ranging from non-toxic), the number of lipid droplets,
      lipid content, and triglyceride production, the typical characteristics of
      adipocytes, were suppressed in a concentration-dependent manner. During this
      process, EEAY significantly reduced the expression of adipogenic transcription
      factors, including peroxisome proliferator-activated receptor-gamma,
      CCAAT/enhancer-binding protein alpha and beta, and sterol regulatory element
      binding protein-1c. In addition, EEAY was also found to potently inhibit the
      expression of adipocyte-specific genes, including adipocyte fatty acid-binding
      protein and leptin. In particular, EEAY treatment effectively enhanced the
      activation of the AMP-activated protein kinase (AMPK) signaling pathway; however,
      the co-treatment with compound C, an inhibitor of AMPK, significantly restored
      the EEAY-induced inhibition of pro-adipogenic transcription factors and adipocyte
      specific genes. These results indicate that EEAY may exert an anti-obesity effect
      by controlling the AMPK signaling pathway, suggesting that the leaf extract of A.
      yomena may be a potential anti-obesity agent.

PMID- 29021505
TI  - Skin permeability of tulobuterol in two transdermal formulations and their
      followability.
AB  - Various generic transdermal formulations of tulobuterol containing rubber and
      acrylate base polymers are commercially available in Japan. However, none of the
      formulations have been compared directly with respect to the skin permeability of
      tulobuterol and to their follow ability. Tulobuterol Tape Sawai of rubber base
      and Tulobuterol Tape NP of acrylate base were used to conduct the in vitro 24
      hour skin permeability test of tulobuterol at receiver solution temperatures of
      32 degrees C, 37 degrees C, and 40 degrees C. Furthermore, the followability of
      these tapes were examined by measuring the depth of the pores that were formed in
      their adhesive layer. Consequently, the maximum flux of tulobuterol was greater
      for Tulobuterol Tape NP. Arrhenius plot analysis revealed that Tulobuterol Tape
      Sawai was more sensitive to skin surface temperature compared with Tulobuterol
      Tape NP. Skin abrasion had a greater effect on the skin permeability of
      tulobuterol in Tulobuterol Tape Sawai than in Tulobuterol Tape NP. Followability
      was greater for Tulobuterol Tape NP than for Tulobuterol Tape Sawai. These
      results suggest that a transdermal formulation of acrylate base is preferable to
      that with a rubber base when skin surface temperature varies or when the skin is
      abraded. In clinical settings, therefore, a formulation of acrylate base is
      preferable to a formulation of rubber base when skin surface temperature varies
      or when the skin is abraded. The formulation needs to be applied to the skin of
      less asperity for the achievement of better transdermal absorption of
      tulobuterol.

PMID- 29021506
TI  - Computational wave dynamics for innovative design of coastal structures.
AB  - For innovative designs of coastal structures, Numerical Wave Flumes (NWFs), which
      are solvers of Navier-Stokes equation for free-surface flows, are key tools. In
      this article, various methods and techniques for NWFs are overviewed. In the
      former half, key techniques of NWFs, namely the interface capturing (MAC, VOF, C
      CUP) and significance of NWFs in comparison with the conventional wave models are
      described. In the latter part of this article, recent improvements of the
      particle method are shown as one of cores of NWFs. Methods for attenuating
      unphysical pressure fluctuation and improving accuracy, such as CMPS method for
      momentum conservation, Higher-order Source of Poisson Pressure Equation (PPE),
      Higher-order Laplacian, Error-Compensating Source in PPE, and Gradient Correction
      for ensuring Taylor-series consistency, are reviewed briefly. Finally, the latest
      new frontier of the accurate particle method, including Dynamic Stabilization for
      providing minimum-required artificial repulsive force to improve stability of
      computation, and Space Potential Particle for describing the exact free-surface
      boundary condition, is described.

PMID- 29021507
TI  - Biological control for grapevine crown gall using nonpathogenic Rhizobium vitis
      strain ARK-1.
AB  - Crown gall of grapevine, which is caused by tumorigenic Rhizobium vitis, is the
      most important bacterial disease of grapevine throughout the world. Screening
      tests of biological control agents resulted in the discovery of a nonpathogenic
      R. vitis strain ARK-1. By soaking grapevine roots with a cell suspension of
      strain ARK-1 prior to planting in the field, ARK-1 treatment significantly
      reduced the number of plants with crown gall symptoms. Several field trials
      result indicated that ARK-1 was very useful in the field, not only for grapevine
      but also for various other plant species. In experiments where a mixture of ARK-1
      and a tumorigenic strain at a 1 : 1 cell ratio was examined in vitro and in
      planta, expression levels of the virulence genes virD2 and virE2 of the
      tumorigenic strain were significantly lower. The suppression of virulence genes,
      which can result in a reduction of gall formation and the pathogen population,
      seems to be a unique mechanism of ARK-1. These results indicated that ARK-1 is a
      promising new agent to control grapevine crown gall.

PMID- 29021508
TI  - Comprehensive functional genomics using Caenorhabditis elegans as a model
      organism.
AB  - We have been working on functional genomics using C. elegans as a model organism.
      We first used cell-type specific markers and preexisting mutants to investigate
      how genotype-phenotype causal relationships are regulated. With the aid of
      transgenic methods, we analyzed various biological processes in C. elegans. We
      have developed efficient methods to isolate gene knockout strains. Thousands of
      strains isolated this way are used by many researchers and have revealed many
      biological mechanisms. We have also developed methods to examine the functions of
      genes in a comprehensive manner by integrating transgenes into chromosomes,
      designing conditional knockouts, and creating balancers for lethal mutations. A
      combination of these biological resources and techniques will be useful to
      understand the functions of genes in C. elegans, which has many genes that are
      orthologous to those of higher organisms including humans.

PMID- 29021510
TI  - Treatment of rheumatoid arthritis with biological agents - as a typical and
      common immune-mediated inflammatory disease.
AB  - Molecules involved in the disease process facilitated our understanding of
      pathogenesis of the disease with unknown etiology such as immune-mediated and
      inflammatory diseases. Moreover, the targeted therapies against the proposed
      molecular targets by biological agents provide enormous benefits to the patients
      and societies. Here, I will review recent progress of the biological treatment in
      the immune-inflammatory diseases by focusing on the rheumatoid arthritis, the
      disease characterized by persistent polyarthritis leading to joint destruction
      and disability with autoimmune features, as a role model.

PMID- 29021509
TI  - Nucleotide-binding oligomerization domain 1 and gastrointestinal disorders.
AB  - Nucleotide-binding oligomerization domain 1 (NOD1) is an intracellular sensor
      that detects small peptides derived from the cell wall component of intestinal
      microflora. NOD1 is expressed in both non-hematopoietic cells such as epithelial
      cells and hematopoietic cells such as antigen-presenting cells. Detection of its
      ligand by NOD1 leads to innate immune responses through activation of nuclear
      factor kappa B and type I interferon as well as induction of autophagy. Innate
      immune responses through NOD1 activation play an indispensable role both in host
      defense against microbial infection and in the development of gastrointestinal
      disorders. Of particular importance, NOD1-mediated innate immune responses are
      associated with mucosal host defenses against Helicobacter pylori (H. pylori)
      infection of the stomach and with the development of pancreatitis. In this
      review, we discuss the molecular mechanisms by which NOD1 activation leads to the
      development of H. pylori-related gastric diseases and pancreatitis.

PMID- 29021513
TI  - New synthesis of a stereoisomeric mixture of methyl 12-trishomofarnesoate, a
      juvenile hormone mimic useful in sericulture by increasing silk production.
AB  - A mixture of (E,Z)-isomers of methyl 12-trishomofarnesoate (methyl 3,7,11
      trimethyl-2,6,10-pentadecatrienoate), a juvenile hormone mimic, was synthesized
      in nine steps (32.6% overall yield) by starting from only four commercially
      available materials: 2-hexanone, vinylmagnesium bromide, methyl acetoacetate and
      trimethyl phosphonoacetate. The mimic is useful in increasing the yield of silk
      by elongating the larval period of the silkworm, Bombyx mori (L.).

PMID- 29021512
TI  - Dynamic mechanisms driving conformational conversions of the beta and epsilon
      subunits involved in rotational catalysis of F1-ATPase.
AB  - F-type ATPase is a ubiquitous molecular motor. Investigations on thermophilic F1
      ATPase and its subunits, beta and epsilon, by NMR were reviewed. Using specific
      isotope labeling, pKa of the putative catalytic carboxylate in beta was
      estimated. Segmental isotope-labeling enabled us to monitor most residues of
      beta, revealing that the conformational conversion from open to closed form of
      beta on nucleotide binding found in ATPase was an intrinsic property of beta and
      could work as a driving force of the rotational catalysis. A stepwise
      conformational change was driven by switching of the hydrogen bond networks
      involving Walker A and B motifs. Segmentally labeled ATPase provided a well
      resolved NMR spectra, revealing while the open form of beta was identical for
      beta monomer and ATPase, its closed form could be different. ATP-binding was also
      a critical factor in the conformational conversion of epsilon, an ATP hydrolysis
      inhibitor. Its structural elucidation was described.

PMID- 29021511
TI  - Overcoming sleep disordered breathing and ensuring sufficient good sleep time for
      a healthy life expectancy.
AB  - Recent advances in basic and clinical medicine have resulted in major
      improvements in human health. Currently sleep has been considered an essential
      factor in maintaining and promoting a healthy life expectancy. Sleep disorders
      include more than 60 diseases. Sleep disordered breathings (SDB) have 17
      disorders, including sleep apnea. SDB usually induces hypoxemia and hypercapnia,
      which would have significant effects on cells, organs, and the whole body. We
      have investigated SDB for nearly 35 years. We found that SDB has significant
      associations with humoral factors, including coagulation systems, the body's
      protective factors against diseases, and metabolic and organ diseases. Currently
      we have been giving attention to the associations among SDB, short sleep
      duration, and obesity. In addition, SDB is important not only in the home but
      under critical care such as in the perioperative stage. In this review, I would
      like to describe several aspects of SDB in relation to systemic diseases and
      overall health based mainly on our published reports.

PMID- 29021514
TI  - Characteristics and Prognosis of Patients with Immunoglobulin M Monoclonal
      Gammopathy.
AB  - Many patients with immunoglobulin M (IgM) monoclonal gammopathy remain
      asymptomatic and, consequently, untreated; however, few studies have evaluated
      the clinical course and prognosis of these patients. Using the screening
      procedures at our hospital, 74 patients with IgM monoclonal gammopathy were
      selected. We excluded 11 patients in whom the treatment for lymphoid neoplasms
      had been initiated at the time of IgM monoclonal protein detection. The remaining
      63 patients were considered to be the patient population with IgM MGUS and
      asymptomatic WM, and were analyzed. In these patients, the median overall
      survival was longer than 14 years. More than half of these patients died from
      causes other than lymphoid neoplasm. The cumulative incidence of lymphoid
      neoplasm requiring treatment was 17.5%. In five of eight patients requiring
      treatment for lymphoid neoplasms, the causes of death were related with these
      lymphoid neoplasms. Our study suggests that not all patients with IgM monoclonal
      gammopathy require uniform treatment for prolonged survival; however, most
      lymphoid neoplasms requiring treatment are refractory diseases. Our findings may
      help manage patients with macroglobulinemia.

PMID- 29021515
TI  - Clinicopathological Analysis of 320 Cases of Diffuse Large B-cell Lymphoma Using
      the Hans Classifier.
AB  - The estimation of clinical prognosis for diffuse large B-cell lymphoma (DLBCL)
      with a quick, cost-efficient method is necessary because of the clinical
      heterogeneity of this disease, which leads to death, relapsed or refractory
      disease in approximately 40% of patients. We analyzed 320 cases diagnosed from
      2007 to 2013 treated with R-CHOP therapy at Tokai University Hospital and
      associated institutions. DLBCL was classified according to the cell-of-origin
      using the Hans algorithm [germinal center B-cell-like (GCB) vs non-GCB subtypes],
      and into 6 subgroups derived from combinations of CD10, BCL6 and MUM1 markers.
      The percentage of GCB and non-GCB (NGCB) subtypes was 35% and 65%, respectively.
      GCB-DLBCL was characterized by lower BCL2 immunohistochemical expression,
      extranodal sites <1, better therapeutic response, and favorable overall survival
      (OS) and progression free survival (PFS) (P<0.01). The most frequent subgroup was
      NGCB-1 (CD10-BCL6+MUM1+, 51%) followed by GCB-1 (CD10+BCL6+or-MUM1+, 21%), NGCB-2
      (CD10-BCL6-MUM1+, 13%), GCB-2 (CD10+BCL6+or-MUM1-, 10%), GCB-3 (CD10-BCL6+MUM1-,
      4%) and NGCB-3 (CD10-BCL6-MUM1-, 2%). In comparison with GCB-2 and GCB-3 (both
      MUM1-), the GCB-1 (MUM1+) was characterized by favorable PFS (5-year PFS 84% vs
      65%, OR 0.368, P<0.05), independent of high LDH (associated with unfavorable PFS,
      OR 7.04, P<0.01) in the multivariate analysis. This predictive value of MUM1 was
      independent of CD10. Interestingly, triple-negative NGCB-3 tended to have a more
      favorable prognosis than the other NGCB subgroups. In conclusion, the Hans
      classifier is a valid method to evaluate the prognosis of DLBCL NOS. In the GCB
      subtypes, GCB subtypes, MUM1-positivity is associated with a more favorable
      outcome (PFS).

PMID- 29021517
TI  - A RARE CASE OF MIXED PHENOTYPE ACUTE LEUKEMIA- B/T CELL TYPE.

PMID- 29021516
TI  - Human herpesvirus 8-unrelated primary effusion lymphoma-like lymphoma following
      tyrosine kinase inhibitor treatment for chronic myelogenous leukemia.
AB  - A 69-year-old man was diagnosed with chronic myelogenous leukemia (CML) and
      treated with dasatinib. After two years on dasatinib, the patient achieved
      complete molecular response, but dasatinib treatment was discontinued due to
      exacerbation of pleural effusion. Nilotinib and imatinib were started but stopped
      due to an increase in pleural effusion. Thoracentesis was performed and he was
      diagnosed with human herpesvirus 8-unrelated primary effusion lymphoma (PEL)-like
      lymphoma. Complex chromosomal abnormality, including BCL6 rearrangement, was
      found on chromosome analysis. To the best of our knowledge, this is the first
      report of PEL-like lymphoma following tyrosine kinase inhibitor treatment for
      CML.

PMID- 29021518
TI  - The Lethal Spanish Influenza Pandemic in Poland.
AB  - The Spanish influenza pandemic in the years 1918-1920 was the largest and most
      tragic pandemic of infectious disease in human history. Deciphering the structure
      of the virus (including the determination of complete genome sequence) of this
      pandemic and the phylogenetic analysis and explanation of its virulence became
      possible thanks to molecular genetic analysis of the virus isolated from the
      fixed and frozen lung tissue of influenza victims who died in 1918 and were
      buried frozen in Alaska and Spitsbergen. Epidemiological data from the course of
      this pandemic in Poland have not been previously published. For analysis, we used
      source materials such as clinical studies and case reports of doctors fighting
      against the pandemic and registries of influenza cases in units of the Polish
      Army and military hospitals. Clinically, the pandemic of 1918 was characterized
      by the same symptoms and course as influenza in other years. Pathologically, the
      disease was similar to the other pandemic, in that the destruction was mostly
      limited to the respiratory tract. The "Spanish" influenza pandemic of 1918-1920
      took place in Poland in 3 epidemic waves. The peaks of morbidity and mortality
      occurred in the capital, Warsaw, in December 1918 and in December 1919 to January
      1920. It is estimated that throughout the pandemic period of 1918-1920 in Poland,
      200 000 to 300 000 people died.

PMID- 29021519
TI  - Bone Marrow Mononuclear Cells Transplantation in Treatment of Established
      Bronchopulmonary Dysplasia: A Case Report.
AB  - BACKGROUND Bronchopulmonary dysplasia (BDP) is an incurable disease. This study
      reports the successful treatment of a 30-week-old neonate with established
      bronchopulmonary dysplasia by bone marrow mononuclear cells (BM MNCs)
      transplantation. CASE REPORT The preterm infant with BPD requiring continuous
      oxygen administration for 4 months post-delivery underwent BM MNCs. Bone marrow
      was obtained from the patient's iliac crests and mononuclear cells were isolated
      by density gradient centrifugation method. BM MNCs were delivered via
      endotracheal and intravenous routes. After BM MNCs transplantation, remarkable
      improvements were observed in oxygen saturation and lung CT as the infant was
      gradually weaned off oxygen supply. CONCLUSIONS BM MNCs transplantation offers
      promising treatment of BPD.

PMID- 29021520
TI  - HDAC6 inhibition reverses axonal transport defects in motor neurons derived from
      FUS-ALS patients.
AB  - Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative
      disorder due to selective loss of motor neurons (MNs). Mutations in the fused in
      sarcoma (FUS) gene can cause both juvenile and late onset ALS. We generated and
      characterized induced pluripotent stem cells (iPSCs) from ALS patients with
      different FUS mutations, as well as from healthy controls. Patient-derived MNs
      show typical cytoplasmic FUS pathology, hypoexcitability, as well as progressive
      axonal transport defects. Axonal transport defects are rescued by CRISPR/Cas9
      mediated genetic correction of the FUS mutation in patient-derived iPSCs.
      Moreover, these defects are reproduced by expressing mutant FUS in human
      embryonic stem cells (hESCs), whereas knockdown of endogenous FUS has no effect,
      confirming that these pathological changes are mutant FUS dependent.
      Pharmacological inhibition as well as genetic silencing of histone deacetylase 6
      (HDAC6) increase alpha-tubulin acetylation, endoplasmic reticulum (ER)
      mitochondrial overlay, and restore the axonal transport defects in patient
      derived MNs.Amyotrophic lateral sclerosis (ALS) leads to selective loss of motor
      neurons. Using motor neurons derived from induced pluripotent stem cells from
      patients with ALS and FUS mutations, the authors demonstrate that axonal
      transport deficits that are observed in these cells can be rescued by HDAC6
      inhibition.

PMID- 29021521
TI  - Tristetraprolin inhibits macrophage IL-27-induced activation of antitumour
      cytotoxic T cell responses.
AB  - IFN-gamma-producing cytotoxic T lymphocytes are essential for host defense
      against viral infection and cancer. Here we show that the RNA-binding
      tristetraprolin, encoded by Zfp36, is needed for CD8+ T-cell production of IFN
      gamma in vivo. When activated in vitro, however, IFN-gamma production by naive
      wild type and tristetraprolin-deficient CD8+ T-cells is comparable. IL-27 is
      overproduced by tristetraprolin-deficient macrophages and increased systemically
      in tristetraprolin-deficient mice. Tristetraprolin suppresses IL-27 production by
      promoting p28 mRNA degradation. Importantly, deletion of IL-27 receptor WSX-1 in
      tristetraprolin-deficient mice (WSX-1/tristetraprolin double knockout) leads to a
      reduction in cytotoxic T lymphocyte numbers. Moreover, tumor growth is
      accelerated, not only in tristetraprolin-deficient mice after cytotoxic T
      lymphocyte depletion, but also in WSX-1/tristetraprolin double knockout mice,
      with substantial reduction in the number of tumor cytotoxic T lymphocytes. This
      study describes a regulatory pathway for IL-27 expression and cytotoxic T
      lymphocyte function mediated by tristetraprolin, contributing to regulation of
      antitumour immunity.IL-27 is one of a number of cytokines that can induce
      antitumour CD8+ T cell responses. Here the authors show that TTP, encoded by
      Zfp36, degrades p28 to inhibit IL-27 production by macrophages and is thereby a
      negative regulator of the antitumour response.

PMID- 29021522
TI  - The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer
      metastasis through its actions on immune cells.
AB  - Obesity and elevated circulating cholesterol are risk factors for breast cancer
      recurrence, while the use of statins, cholesterol biosynthesis inhibitors widely
      used for treating hypercholesterolemia, is associated with improved disease-free
      survival. Here, we show that cholesterol mediates the metastatic effects of a
      high-fat diet via its oxysterol metabolite, 27-hydroxycholesterol. Ablation or
      inhibition of CYP27A1, the enzyme responsible for the rate-limiting step in 27
      hydroxycholesterol biosynthesis, significantly reduces metastasis in relevant
      animal models of cancer. The robust effects of 27-hydroxycholesterol on
      metastasis requires myeloid immune cell function, and it was found that this
      oxysterol increases the number of polymorphonuclear-neutrophils and gammadelta-T
      cells at distal metastatic sites. The pro-metastatic actions of 27
      hydroxycholesterol requires both polymorphonuclear-neutrophils and gammadelta-T
      cells, and 27-hydroxycholesterol treatment results in a decreased number of
      cytotoxic CD8+T lymphocytes. Therefore, through its actions on gammadelta-T cells
      and polymorphonuclear-neutrophils, 27-hydroxycholesterol functions as a
      biochemical mediator of the metastatic effects of hypercholesterolemia.High
      cholesterol is a risk factor for breast cancer recurrence. Here the authors show
      that cholesterol promotes breast cancer metastasis via its metabolite 27
      hydroxycholesterol (27HC) that acts on immune myeloid cells residing at the
      distal metastatic sites, thus promoting an immune suppressive environment.

PMID- 29021525
TI  - Danshenol A inhibits TNF-alpha-induced expression of intercellular adhesion
      molecule-1 (ICAM-1) mediated by NOX4 in endothelial cells.
AB  - ICAM-1 overexpression and subsequent adhesion of leukocytes to endothelial cells
      play critical roles in the early stage of atherosclerosis. Danshenol A (DA) is an
      abietane-type diterpenoid isolated from traditional Chinese herb Salvia
      miltiorrhiza Bunge. The mechanisms under its regulation of adhesion of molecular
      expression are explored. Here, the effect of DA on TNF-alpha-induced ICAM-1
      expression was investigated in endothelial cells. TNF-alpha-induced ICAM-1
      expression and subsequent adhesion of monocytes, as well as elevated reactive
      oxygen species (ROS) generation and NOX4 expression were all significantly
      reversed by DA, siNOX4 and NOX4 inhibitor GKT137831. Furthermore, TNF-alpha
      induced ICAM-1 expression, which was increased via IKKbeta/IkappaBalpha-mediated
      activation of NF-kappaB p65, was also inhibited by DA. Interestingly, NOX4
      overexpression suppressed the ICAM-1 expression, and this finding may be ascribed
      to the activation of Nrf-2. Additionally, NF-kappaB inhibitor PDTC, siNOX4, or DA
      can decrease the TNF-alpha-induced ICAM-1 expression and suppress the adhesion of
      monocytes. In all, DA inhibited TNF-alpha-induced ICAM-1 expression and
      subsequent monocyte adhesion to endothelial cells through the NOX4-dependent
      IKKbeta/NF-kappaB pathway. Besides, NOX4 played dual role in regulating ICAM-1
      expression via diverse signal pathway. This novel bioactivity will make DA a good
      candidate to be further explored for therapeutic or preventive application for
      atherosclerosis.

PMID- 29021523
TI  - High-fidelity DNA replication in Mycobacterium tuberculosis relies on a
      trinuclear zinc center.
AB  - High-fidelity DNA replication depends on a proofreading 3'-5' exonuclease that is
      associated with the replicative DNA polymerase. The replicative DNA polymerase
      DnaE1 from the major pathogen Mycobacterium tuberculosis (Mtb) uses its intrinsic
      PHP-exonuclease that is distinct from the canonical DEDD exonucleases found in
      the Escherichia coli and eukaryotic replisomes. The mechanism of the PHP
      exonuclease is not known. Here, we present the crystal structure of the Mtb DnaE1
      polymerase. The PHP-exonuclease has a trinuclear zinc center, coordinated by nine
      conserved residues. Cryo-EM analysis reveals the entry path of the primer strand
      in the PHP-exonuclease active site. Furthermore, the PHP-exonuclease shows a
      striking similarity to E. coli endonuclease IV, which provides clues regarding
      the mechanism of action. Altogether, this work provides important insights into
      the PHP-exonuclease and reveals unique properties that make it an attractive
      target for novel anti-mycobacterial drugs.The polymerase and histidinol
      phosphatase (PHP) domain in the DNA polymerase DnaE1 is essential for
      mycobacterial high-fidelity DNA replication. Here, the authors determine the
      DnaE1 crystal structure, which reveals the PHP-exonuclease mechanism that can be
      exploited for antibiotic development.

PMID- 29021524
TI  - Ecogenomics of virophages and their giant virus hosts assessed through time
      series metagenomics.
AB  - Virophages are small viruses that co-infect eukaryotic cells alongside giant
      viruses (Mimiviridae) and hijack their machinery to replicate. While two types of
      virophages have been isolated, their genomic diversity and ecology remain largely
      unknown. Here we use time series metagenomics to identify and study the dynamics
      of 25 uncultivated virophage populations, 17 of which represented by complete or
      near-complete genomes, in two North American freshwater lakes. Taxonomic analysis
      suggests that these freshwater virophages represent at least three new candidate
      genera. Ecologically, virophage populations are repeatedly detected over years
      and evolutionary stable, yet their distinct abundance profiles and gene content
      suggest that virophage genera occupy different ecological niches. Co-occurrence
      analyses reveal 11 virophages strongly associated with uncultivated Mimiviridae,
      and three associated with eukaryotes among the Dinophyceae, Rhizaria, Alveolata,
      and Cryptophyceae groups. Together, these findings significantly augment
      virophage databases, help refine virophage taxonomy, and establish baseline
      ecological hypotheses and tools to study virophages in nature.Virophages are
      recently-identified small viruses that infect larger viruses, yet their diversity
      and ecological roles are poorly understood. Here, Roux and colleagues present
      time series metagenomics data revealing new virophage genera and their putative
      ecological interactions in two freshwater lakes.

PMID- 29021526
TI  - Anodal tDCS applied during multitasking training leads to transferable
      performance gains.
AB  - Cognitive training can lead to performance improvements that are specific to the
      tasks trained. Recent research has suggested that transcranial direct current
      stimulation (tDCS) applied during training of a simple response-selection
      paradigm can broaden performance benefits to an untrained task. Here we assessed
      the impact of combined tDCS and training on multitasking, stimulus-response
      mapping specificity, response-inhibition, and spatial attention performance in a
      cohort of healthy adults. Participants trained over four days with concurrent
      tDCS - anodal, cathodal, or sham - applied to the left prefrontal cortex.
      Immediately prior to, 1 day after, and 2 weeks after training, performance was
      assessed on the trained multitasking paradigm, an untrained multitasking
      paradigm, a go/no-go inhibition task, and a visual search task. Training combined
      with anodal tDCS, compared with training plus cathodal or sham stimulation,
      enhanced performance for the untrained multitasking paradigm and visual search
      tasks. By contrast, there were no training benefits for the go/no-go task. Our
      findings demonstrate that anodal tDCS combined with multitasking training can
      extend to untrained multitasking paradigms as well as spatial attention, but with
      no extension to the domain of response inhibition.

PMID- 29021527
TI  - Operando Multi-modal Synchrotron Investigation for Structural and Chemical
      Evolution of Cupric Sulfide (CuS) Additive in Li-S battery.
AB  - Conductive metal sulfides are promising multi-functional additives for future
      lithium-sulfur (Li-S) batteries. These can increase the sulfur cathode's
      electrical conductivity to improve the battery's power capability, as well as
      contribute to the overall cell-discharge capacity. This multi-functional
      electrode design showed initial promise; however, complicated interactions at the
      system level are accompanied by some detrimental side effects. The metal sulfide
      additives with a chemical conversion as the reaction mechanism, e.g., CuS and
      FeS2, can increase the theoretical capacity of the Li-S system. However, these
      additives may cause undesired parasitic reactions, such as the dissolution of the
      additive in the electrolyte. Studying such complex reactions presents a challenge
      because it requires experimental methods that can track the chemical and
      structural evolution of the system during an electrochemical process. To address
      the fundamental mechanisms in these systems, we employed an operando multimodal x
      ray characterization approach to study the structural and chemical evolution of
      the metal sulfide-utilizing powder diffraction and fluorescence imaging to
      resolve the former and absorption spectroscopy the latter-during lithiation and
      de-lithiation of a Li-S battery with CuS as the multi-functional cathode
      additive. The resulting elucidation of the structural and chemical evolution of
      the system leads to a new description of the reaction mechanism.

PMID- 29021528
TI  - Forecasting the onset and course of mental illness with Twitter data.
AB  - We developed computational models to predict the emergence of depression and Post
      Traumatic Stress Disorder in Twitter users. Twitter data and details of
      depression history were collected from 204 individuals (105 depressed, 99
      healthy). We extracted predictive features measuring affect, linguistic style,
      and context from participant tweets (N = 279,951) and built models using these
      features with supervised learning algorithms. Resulting models successfully
      discriminated between depressed and healthy content, and compared favorably to
      general practitioners' average success rates in diagnosing depression, albeit in
      a separate population. Results held even when the analysis was restricted to
      content posted before first depression diagnosis. State-space temporal analysis
      suggests that onset of depression may be detectable from Twitter data several
      months prior to diagnosis. Predictive results were replicated with a separate
      sample of individuals diagnosed with PTSD (Nusers = 174, Ntweets = 243,775). A
      state-space time series model revealed indicators of PTSD almost immediately post
      trauma, often many months prior to clinical diagnosis. These methods suggest a
      data-driven, predictive approach for early screening and detection of mental
      illness.

PMID- 29021529
TI  - Endogenously generated 2-aminoacrylate inhibits motility in Salmonella enterica.
AB  - Members of the broadly distributed Rid/YER057c/UK114 protein family have
      imine/enamine deaminase activity, notably on 2-aminoacrylate (2AA). Strains of
      Salmonella enterica, and other organisms lacking RidA, have diverse growth
      phenotypes, attributed to the accumulation of 2AA. In S. enterica, 2AA
      inactivates a number of pyridoxal 5'-phosephate(PLP)-dependent enzymes, some of
      which have been linked to the growth phenotypes of a ridA mutant. This study used
      transcriptional differences between S. enterica wild-type and ridA strains to
      explore the breadth of the cellular consequences that resulted from accumulation
      of 2AA. Accumulation of endogenously generated 2AA in a ridA mutant resulted in
      lower expression of genes encoding many flagellar assembly components, which led
      to a motility defect. qRT-PCR results were consistent with the motility phenotype
      of a ridA mutant resulting from a defect in FlhD4C2 activity. In total, the
      results of comparative transcriptomics correctly predicted a 2AA-dependent
      motility defect and identified additional areas of metabolism impacted by the
      metabolic stress of 2AA in Salmonella enterica. Further, the data emphasized the
      value of integrating global approaches with biochemical genetic approaches to
      understand the complex system of microbial metabolism.

PMID- 29021530
TI  - SHH signaling directed by two oral epithelium-specific enhancers controls tooth
      and oral development.
AB  - Interaction between the epithelium and mesenchyme coordinates patterning and
      differentiation of oral cavity structures including teeth, palatal rugae and
      tongue papillae. SHH is one of the key signaling molecules for this interaction.
      Epithelial expression of Shh in the tooth buds and tongue papillae is regulated
      by at least two enhancers, MRCS1 and MFCS4. However, it is unclear how the two
      enhancers cooperate to regulate Shh. Here, we found that simultaneous deletion of
      MRCS1 and MFCS4 results in the formation of a supernumerary tooth in front of the
      first molar. Since deletion of either single enhancer barely affects tooth
      development, MRCS1 and MFCS4 evidently act in a redundant fashion. Binding motifs
      for WNT signaling mediators are shared by MRCS1 and MFCS4, and play a central
      role in regulating Shh expression, indicating that the two redundant enhancers
      additively exert their Shh regulation by responding to WNT signal input.

PMID- 29021531
TI  - Correlation of X-ray diffraction signatures of breast tissue and their
      histopathological classification.
AB  - This pilot study examines the correlation of X-ray diffraction (XRD) measurements
      with the histopathological analysis of breast tissue. Eight breast cancer samples
      were investigated. Each sample contained a mixture of normal and cancerous
      tissues. In total, 522 separate XRD measurements were made at different locations
      across the samples (8 in total). The resulting XRD spectra were subjected to
      principal component analysis (PCA) in order to determine if there were any
      distinguishing features that could be used to identify different tissue
      components. 99.0% of the variation between the spectra were described by the
      first two principal components (PC). Comparing the location of points in PC space
      with the classification determined by histopathology indicated correlation
      between the shape/magnitude of the XRD spectra and the tissue type. These results
      are encouraging and suggest that XRD could be used for the intraoperative or
      postoperative classification of bulk tissue samples.

PMID- 29021532
TI  - Monocyte-lymphocyte cross-communication via soluble CD163 directly links innate
      immune system activation and adaptive immune system suppression following
      ischemic stroke.
AB  - CD163 is a scavenger receptor expressed on innate immune cell populations which
      can be shed from the plasma membrane via the metalloprotease ADAM17 to generate a
      soluble peptide with lympho-inhibitory properties. The purpose of this study was
      to investigate CD163 as a possible effector of stroke-induced adaptive immune
      system suppression. Liquid biopsies were collected from ischemic stroke patients
      (n = 39), neurologically asymptomatic controls (n = 20), and stroke mimics (n =
      20) within 24 hours of symptom onset. Peripheral blood ADAM17 activity and
      soluble CD163 levels were elevated in stroke patients relative to non-stroke
      control groups, and negatively associated with post-stroke lymphocyte counts.
      Subsequent in vitro experiments suggested that this stroke-induced elevation in
      circulating soluble CD163 likely originates from activated monocytic cells, as
      serum from stroke patients stimulated ADAM17-dependant CD163 shedding from
      healthy donor-derived monocytes. Additional in vitro experiments demonstrated
      that stroke-induced elevations in circulating soluble CD163 can elicit direct
      suppressive effects on the adaptive immune system, as serum from stroke patients
      inhibited the proliferation of healthy donor-derived lymphocytes, an effect which
      was attenuated following serum CD163 depletion. Collectively, these observations
      provide novel evidence that the innate immune system employs protective
      mechanisms aimed at mitigating the risk of post-stroke autoimmune complications
      driven by adaptive immune system overactivation, and that CD163 is key mediator
      of this phenomenon.

PMID- 29021533
TI  - An integrated microfluidic system using a micro-fluxgate and micro spiral coil
      for magnetic microbeads trapping and detecting.
AB  - We report an innovative integrated microfluidic platform based on micro-fluxgate
      and micro-coils for trapping and detecting magnetic beads. A micro-spiral coil
      fabricated by microfabrication technology is used to trap the magnetic beads, and
      the micro-fluxgate is employed to detect the weak magnetic field induced by the
      trapped magnetic beads. The fabrication process of the magnetic bead trapping
      system using a micro-coil is highly compatible with that of the micro-fluxgate
      sensor, making fabrication of this integrated microfluidic system convenient and
      efficient. It is observed that the magnetic bead trapping ratio increases as the
      number of magnetic beads is increased with a flow rate of 5 to 16.5 MUL.min-1.
      Samples spiked with different concentrations of magnetic beads can be
      distinguished clearly using the micro-fluxgate sensor in this microfluidic
      system. In this study, the results demonstrate that the microfluidic system traps
      and detects magnetic beads efficiently and is a promising candidate for biomarker
      capture and detection.

PMID- 29021534
TI  - Quorum sensing integrates environmental cues, cell density and cell history to
      control bacterial competence.
AB  - Streptococcus pneumoniae becomes competent for genetic transformation when
      exposed to an autoinducer peptide known as competence-stimulating peptide (CSP).
      This peptide was originally described as a quorum-sensing signal, enabling
      individual cells to regulate competence in response to population density.
      However, recent studies suggest that CSP may instead serve as a probe for sensing
      environmental cues, such as antibiotic stress or environmental diffusion. Here,
      we show that competence induction can be simultaneously influenced by cell
      density, external pH, antibiotic-induced stress, and cell history. Our
      experimental data is explained by a mathematical model where the environment and
      cell history modify the rate at which cells produce or sense CSP. Taken together,
      model and experiments indicate that autoinducer concentration can function as an
      indicator of cell density across environmental conditions, while also
      incorporating information on environmental factors or cell history, allowing
      cells to integrate cues such as antibiotic stress into their quorum-sensing
      response. This unifying perspective may apply to other debated quorum-sensing
      systems.Peptide CSP regulates natural competence in pneumococci and has been
      proposed as a quorum-sensing signal or a probe for sensing environmental cues.
      Here, the authors show that CSP levels can indeed act as an indicator of cell
      density and also incorporate information on environmental factors or cell
      history.

PMID- 29021535
TI  - The autophagy scaffold protein ALFY is critical for the granulocytic
      differentiation of AML cells.
AB  - Acute myeloid leukemia (AML) is a malignancy of myeloid progenitor cells that are
      blocked in differentiation. Acute promyelocytic leukemia (APL) is a rare form of
      AML, which generally presents with a t(15;17) translocation causing expression of
      the fusion protein PML-RARA. Pharmacological doses of all-trans retinoic acid
      (ATRA) induce granulocytic differentiation of APL cells leading to cure rates of
      >80% if combined with conventional chemotherapy. Autophagy is a lysosomal
      degradation pathway for the removal of cytoplasmic content and recycling of
      macromolecules. ATRA induces autophagy in ATRA-sensitive AML and APL cells and
      autophagy inhibition attenuates ATRA-triggered differentiation. In this study, we
      aimed at identifying if the autophagy-linked FYVE-domain containing protein
      (ALFY/WDFY3) is involved in autophagic degradation of protein aggregates
      contributes to ATRA therapy-induced autophagy. We found that ALFY mRNA levels
      increase significantly during the course of ATRA-induced differentiation of APL
      and AML cell lines. Importantly ALFY depletion impairs ATRA-triggered
      granulocytic differentiation of these cells. In agreement with its function in
      aggrephagy, knockdown of ALFY results in reduced ATRA-induced proteolysis. Our
      data further suggest that PML-RARalpha is an autophagy substrate degraded with
      the help of ALFY. In summary, we present a crucial role for ALFY in retinoid
      triggered maturation of AML cells.

PMID- 29021536
TI  - EEG Transients in the Sigma Range During non-REM Sleep Predict Learning in Dogs.
AB  - Sleep spindles are phasic bursts of thalamo-cortical activity, visible in the
      cortex as transient oscillations in the sigma range (usually defined in humans as
      12-14 or 9-16 Hz). They have been associated with sleep-dependent memory
      consolidation and sleep stability in humans and rodents. Occurrence, frequency,
      amplitude and duration of sleep spindles co-vary with age, sex and psychiatric
      conditions. Spindle analogue activity in dogs has been qualitatively described,
      but never quantified and related to function. In the present study we used an
      adjusted version of a detection method previously validated in children to test
      whether detections in the dogs show equivalent functional correlates as described
      in the human literature. We found that the density of EEG transients in the 9-16
      Hz range during non-REM sleep relates to memory and is characterized by sexual
      dimorphism similarly as in humans. The number of transients/minute was larger in
      the learning condition and for female dogs, and correlated with the increase of
      performance during recall. It can be concluded that in dogs, automatic detections
      in the 9-16 Hz range, in particular the slow variant (<13 Hz), are functional
      analogues of human spindles.

PMID- 29021537
TI  - Elevated levels of CCR6+ T helper 22 cells correlate with skin and renal
      impairment in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease with a variety of
      pathological features. Our study investigated the potential role of CCR6+ T cells
      in organ impairment of SLE patients. We analyzed CCR6+/- T cell subset
      populations and compared the concentrations of IL-22, IFN-gamma, TNF-alpha, and
      IL-17A cytokines in 67 patients with newly diagnosed SLE and 26 healthy controls.
      We found that SLE patients had elevated percentages of CCR6+ T, CCR6+ Th22, Th17,
      Th17.1, and CCR6- Th2 cell subsets, along with increased concentrations of IL-22,
      IFN-gamma, TNF-alpha, and IL-17 cytokines. Higher levels of CCR6+ T and CCR6+
      Th22 cells, along with plasma IL-22 were observed in SLE patients with sole skin
      and/or renal impairment. The percentage of Th22 cells also correlated with
      Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI)
      and IgG levels, and inversely correlated with C3 levels in SLE patients with sole
      skin impairment. SLE patients with sole renal impairment showed a correlation
      between the percentage of Th22 cells and ESR levels. Our data indicated that
      CCR6+ Th22 cells may contribute to the pathogenesis of new onset SLE patients
      with skin or renal impairment, and CCR6 may, thus, be a possible therapeutic
      target for SLE treatment.

PMID- 29021538
TI  - The effect of different salivary calcium concentrations on the erosion protection
      conferred by the salivary pellicle.
AB  - Different proportions of mineral ions in saliva can influence the protective
      effect the salivary pellicle provides against dental erosion. To investigate the
      effect of different calcium concentrations in human saliva on the protection
      against enamel erosion, enamel specimens were divided into 8 treatment groups:
      humid chamber (Ctrl); whole mouth stimulated human saliva (HS); artificial saliva
      containing different calcium concentrations (ASlow, ASmedium, AShigh); and
      dialysed human saliva containing different calcium concentrations (DSlow,
      DSmedium, DShigh). The specimens underwent 4 cycles of incubation in the
      treatment group followed by an erosive challenge. Surface hardness and calcium
      release were measured during the cycling process. All DS groups exhibited
      significantly higher enamel surface softening than HS and the corresponding AS
      groups. Among the DS groups, the surface softening was significantly higher in
      DSlow than in DShigh. No significant differences were found within the AS or DS
      groups regarding calcium release. The results of this study indicated that
      erosion protection conferred by saliva depends on an interplay between salivary
      proteins and ions. While both proteins and ions have a positive effect on their
      own, the combination of the two can lead to different degrees of protection or
      even negative effects, depending on the relative concentrations.

PMID- 29021539
TI  - Aerial photography based census of Adelie Penguin and its application in CH4 and
      N2O budget estimation in Victoria Land, Antarctic.
AB  - Penguin guano provides favorable conditions for production and emission of
      greenhouse gases (GHGs). Many studies have been conducted to determine the GHG
      fluxes from penguin colonies, however, at regional scale, there is still no
      accurate estimation of total GHG emissions. We used object-based image analysis
      (OBIA) method to estimate the Adelie penguin (Pygoscelis adeliae) population
      based on aerial photography data. A model was developed to estimate total GHG
      emission potential from Adelie penguin colonies during breeding seasons in 1983
      and 2012, respectively. Results indicated that OBIA method was effective for
      extracting penguin information from aerial photographs. There were 17,120 and
      21,183 Adelie penguin breeding pairs on Inexpressible Island in 1983 and 2012,
      respectively, with overall accuracy of the estimation of 76.8%. The main reasons
      for the increase in Adelie penguin populations were attributed to increase in
      temperature, sea ice and phytoplankton. The average estimated CH4 and N2O
      emissions tended to be increasing during the period from 1983 to 2012 and CH4 was
      the main GHG emitted from penguin colonies. Total global warming potential (GWP)
      of CH4 and N2O emissions was 5303 kg CO2-eq in 1983 and 6561 kg CO2-eq in 2012,
      respectively.

PMID- 29021540
TI  - Efficient Single-Photon Coupling from a Nitrogen-Vacancy Center Embedded in a
      Diamond Nanowire Utilizing an Optical Nanofiber.
AB  - Nitrogen-Vacancy (NV) centers in diamond are promising solid-state quantum
      emitters that can be utilized for photonic quantum applications. Various diamond
      nanophotonic devices have been fabricated for efficient extraction of single
      photons emitted from NV centers to a single guided mode. However, for
      constructing scalable quantum networks, further efficient coupling of single
      photons to a guided mode of a single-mode fiber (SMF) is indispensable and a
      difficult challenge. Here, we propose a novel efficient hybrid system between an
      optical nanofiber and a cylindrical-structured diamond nanowire. The maximum
      coupling efficiency as high as 75% for the sum of both fiber ends is obtained by
      numerical simulations. The proposed hybrid system will provide a simple and
      efficient interface between solid-state quantum emitters and a SMF suitable for
      constructing scalable quantum networks.

PMID- 29021541
TI  - Trade routes and plague transmission in pre-industrial Europe.
AB  - Numerous historical works have mentioned that trade routes were to blame for the
      spread of plague in European history, yet this relationship has never been tested
      by quantitative evidence. Here, we resolve the hypothetical role of trade routes
      through statistical analysis on the geo-referenced major trade routes in the
      early modern period and the 6,656 geo-referenced plague outbreak records in
      AD1347-1760. Ordinary Least Square (OLS) estimation results show that major trade
      routes played a dominant role in spreading plague in pre-industrial Europe.
      Furthermore, the negative correlation between plague outbreaks and their distance
      from major trade ports indicates the absence of a permanent plague focus in the
      inland areas of Europe. Major trade routes decided the major plague outbreak
      hotspots, while navigable rivers determined the geographic pattern of sporadic
      plague cases. A case study in Germany indicates that plague penetrated further
      into Europe through the local trade route network. Based on our findings, we
      propose the mechanism of plague transmission in historical Europe, which is
      imperative in demonstrating how pandemics were spread in recent human history.

PMID- 29021542
TI  - Self-assembly of a parallelogram black phosphorus ribbon into a nanotube.
AB  - A nanotube from single-layer black phosphorus (BP) has never been discovered in
      experiments. The present study proposed a method for the fabrication of a BP
      nanotube (BPNT) from a parallelogram nanoribbon self-assembled on a carbon
      nanotube (CNT). The nanoribbon has a pair of opposite sides along the third
      principal direction. According to the numerical simulation via molecular dynamics
      approach, we discover that a wider BP nanoribbon can form into a series of chiral
      nanotube by self-assembly upon CNTs with different radii. The radius of a BPNT
      from the same ribbon has a wide range, and depends on both geometry of the ribbon
      and the CNT. One can obtain a BPNT with the specified radius by placing the
      ribbon nearby a given CNT. The method provides a clue for potential fabrication
      of BPNTs.

PMID- 29021543
TI  - Robust quantum switch with Rydberg excitations.
AB  - We develop an approach to realize a quantum switch for Rydberg excitation in
      atoms with Y- typed level configuration. We find that the steady population on
      two different Rydberg states can be reversibly exchanged in a controllable way by
      properly tuning the Rydberg-Rydberg interaction. Moreover, our numerical
      simulations verify that the switching scheme is robust against spontaneous decay,
      environmental disturbance, as well as the duration of operation on the
      interaction, and also a high switching efficiency is quite attainable, which
      makes it have potential applications in quantum information processing and other
      Rydberg-based quantum technologies.

PMID- 29021544
TI  - Selective catalytic dehydration of furfuryl alcohol to 2, 2'-difurfuryl ether
      using a polyoxometalate catalyst.
AB  - The spice flavour compound 2, 2'-difurfuryl ether (DFE) is widely utilised in the
      food industry as it has a coffee-like, nutty, earthy, mushroom-like odour.
      However, despite intensive research efforts, to date, an environmentally friendly
      and practical synthetic preparation technique for 2, 2'-difurfuryl ether is still
      unavailable. Here, we investigate a new approach using polyoxometalate catalysts
      to selectively catalytically dehydrate furfuryl alcohol to 2, 2'-difurfuryl
      ether. We have successfully applied this methodology using the polyoxometalate
      (POMs) catalyst {[(CH3CH2CH2CH2)4N]2[SMo12O40]} to produce 2,2'-difurfuryl ether
      in a 30.86% isolated yield.

PMID- 29021546
TI  - Functional maturation in preterm infants measured by serial recording of cortical
      activity.
AB  - Minimally invasive, automated cot-side tools for monitoring early neurological
      development can be used to guide individual treatment and benchmark novel
      interventional studies. We develop an automated estimate of the EEG maturational
      age (EMA) for application to serial recordings in preterm infants. The EMA
      estimate was based on a combination of 23 computational features estimated from
      both the full EEG recording and a period of low EEG activity (46 features in
      total). The combination function (support vector regression) was trained using
      101 serial EEG recordings from 39 preterm infants with a gestational age less
      than 28 weeks and normal neurodevelopmental outcome at 12 months of age. EEG
      recordings were performed from 24 to 38 weeks post-menstrual age (PMA). The
      correlation between the EMA and the clinically determined PMA at the time of EEG
      recording was 0.936 (95%CI: 0.932-0.976; n = 39). All infants had an increase in
      EMA between the first and last EEG recording and 57/62 (92%) of repeated measures
      within an infant had an increasing EMA with PMA of EEG recording. The EMA is a
      surrogate measure of age that can accurately determine brain maturation in
      preterm infants.

PMID- 29021547
TI  - Photonic Sorting of Aligned, Crystalline Carbon Nanotube Textiles.
AB  - Floating catalyst chemical vapor deposition uniquely generates aligned carbon
      nanotube (CNT) textiles with individual CNT lengths magnitudes longer than
      competing processes, though hindered by impurities and intrinsic/extrinsic
      defects. We present a photonic-based post-process, particularly suited for these
      textiles, that selectively removes defective CNTs and other carbons not forming a
      threshold thermal pathway. In this method, a large diameter laser beam rasters
      across the surface of a partly aligned CNT textile in air, suspended from its
      ends. This results in brilliant, localized oxidation, where remaining material is
      an optically transparent film comprised of few-walled CNTs with profound and
      unique improvement in microstructure alignment and crystallinity. Raman
      spectroscopy shows substantial D peak suppression while preserving radial
      breathing modes. This increases the undoped, specific electrical conductivity at
      least an order of magnitude to beyond that of single-crystal graphite. Cryogenic
      conductivity measurements indicate intrinsic transport enhancement, opposed to
      simply removing nonconductive carbons/residual catalyst.

PMID- 29021545
TI  - The metabolic enzyme fructose-1,6-bisphosphate aldolase acts as a transcriptional
      regulator in pathogenic Francisella.
AB  - The enzyme fructose-bisphosphate aldolase occupies a central position in
      glycolysis and gluconeogenesis pathways. Beyond its housekeeping role in
      metabolism, fructose-bisphosphate aldolase has been involved in additional
      functions and is considered as a potential target for drug development against
      pathogenic bacteria. Here, we address the role of fructose-bisphosphate aldolase
      in the bacterial pathogen Francisella novicida. We demonstrate that fructose
      bisphosphate aldolase is important for bacterial multiplication in macrophages in
      the presence of gluconeogenic substrates. In addition, we unravel a direct role
      of this metabolic enzyme in transcription regulation of genes katG and rpoA,
      encoding catalase and an RNA polymerase subunit, respectively. We propose a model
      in which fructose-bisphosphate aldolase participates in the control of host redox
      homeostasis and the inflammatory immune response.The enzyme fructose-bisphosphate
      aldolase (FBA) plays central roles in glycolysis and gluconeogenesis. Here,
      Ziveri et al. show that FBA of the pathogen Francisella novicida acts, in
      addition, as a transcriptional regulator and is important for bacterial
      multiplication in macrophages.

PMID- 29021548
TI  - A self-avoiding walk with neural delays as a model of fixational eye movements.
AB  - Fixational eye movements show scaling behaviour of the positional mean-squared
      displacement with a characteristic transition from persistence to antipersistence
      for increasing time-lag. These statistical patterns were found to be mainly
      shaped by microsaccades (fast, small-amplitude movements). However, our re
      analysis of fixational eye-movement data provides evidence that the slow
      component (physiological drift) of the eyes exhibits scaling behaviour of the
      mean-squared displacement that varies across human participants. These results
      suggest that drift is a correlated movement that interacts with microsaccades.
      Moreover, on the long time scale, the mean-squared displacement of the drift
      shows oscillations, which is also present in the displacement auto-correlation
      function. This finding lends support to the presence of time-delayed feedback in
      the control of drift movements. Based on an earlier non-linear delayed feedback
      model of fixational eye movements, we propose and discuss different versions of a
      new model that combines a self-avoiding walk with time delay. As a result, we
      identify a model that reproduces oscillatory correlation functions, the
      transition from persistence to antipersistence, and microsaccades.

PMID- 29021550
TI  - The effects of heterogeneity on stochastic cycles in epidemics.
AB  - Models of biological processes are often subject to different sources of noise.
      Developing an understanding of the combined effects of different types of
      uncertainty is an open challenge. In this paper, we study a variant of the
      susceptible-infective-recovered model of epidemic spread, which combines both
      agent-to-agent heterogeneity and intrinsic noise. We focus on epidemic cycles,
      driven by the stochasticity of infection and recovery events, and study in detail
      how heterogeneity in susceptibilities and propensities to pass on the disease
      affects these quasi-cycles. While the system can only be described by a large
      hierarchical set of equations in the transient regime, we derive a reduced closed
      set of equations for population-level quantities in the stationary regime. We
      analytically obtain the spectra of quasi-cycles in the linear-noise
      approximation. We find that the characteristic frequency of these cycles is
      typically determined by population averages of susceptibilities and
      infectivities, but that their amplitude depends on higher-order moments of the
      heterogeneity. We also investigate the synchronisation properties and phase lag
      between different groups of susceptible and infected individuals.

PMID- 29021549
TI  - Protease resistance of porcine acidic mammalian chitinase under gastrointestinal
      conditions implies that chitin-containing organisms can be sustainable dietary
      resources.
AB  - Chitin, a polymer of N-acetyl-D-glucosamine (GlcNAc), is a major structural
      component in chitin-containing organism including crustaceans, insects and fungi.
      Mammals express two chitinases, chitotriosidase (Chit1) and acidic mammalian
      chitinase (AMCase). Here, we report that pig AMCase is stable in the presence of
      other digestive proteases and functions as chitinolytic enzyme under the
      gastrointestinal conditions. Quantification of chitinases expression in pig
      tissues using quantitative real-time PCR showed that Chit1 mRNA was highly
      expressed in eyes, whereas the AMCase mRNA was predominantly expressed in stomach
      at even higher levels than the housekeeping genes. AMCase purified from pig
      stomach has highest activity at pH of around 2-4 and remains active at up to pH
      7.0. It was resistant to robust proteolytic activities of pepsin at pH 2.0 and
      trypsin and chymotrypsin at pH 7.6. AMCase degraded polymeric chitin substrates
      including mealworm shells to GlcNAc dimers. Furthermore, we visualized chitin
      digestion of fly wings by endogenous AMCase and pepsin in stomach extract. Thus,
      pig AMCase can function as a protease resistant chitin digestive enzyme at broad
      pH range present in stomach as well as in the intestine. These results indicate
      that chitin-containing organisms may be a sustainable feed ingredient in pig
      diet.

PMID- 29021551
TI  - The utility of bioenergetics modelling in quantifying predation rates of marine
      apex predators: Ecological and fisheries implications.
AB  - Predators play a crucial role in the structure and function of ecosystems.
      However, the magnitude of this role is often unclear, particularly for large
      marine predators, as predation rates are difficult to measure directly. If
      relevant biotic and abiotic parameters can be obtained, then bioenergetics
      modelling offers an alternative approach to estimating predation rates, and can
      provide new insights into ecological processes. We integrate demographic and
      ecological data for a marine apex predator, the broadnose sevengill shark
      Notorynchus cepedianus, with energetics data from the literature, to construct a
      bioenergetics model to quantify predation rates on key fisheries species in
      Norfolk Bay, Australia. We account for the uncertainty in model parameters by
      incorporating parameter confidence through Monte Carlo simulations and running
      alternative variants of the model. Model and parameter variants provide
      alternative estimates of predation rates. Our simplest model estimates that ca.
      1130 +/- 137 N. cepedianus individuals consume 11,379 (95% CI: 11,111-11,648)
      gummy sharks Mustelus antarcticus (~21 tonnes) over a 36-week period in Norfolk
      Bay, which represents a considerable contribution to total predation mortality on
      this key fishery species. This study demonstrates how the integration of ecology
      and fisheries science can provide information for ecosystem and fisheries
      management.

PMID- 29021552
TI  - Lifshitz transition from valence fluctuations in YbAl3.
AB  - In mixed-valent Kondo lattice systems, such as YbAl3, interactions between
      localized and delocalized electrons can lead to fluctuations between two
      different valence configurations with changing temperature or pressure. The
      impact of this change on the momentum-space electronic structure is essential for
      understanding their emergent properties, but has remained enigmatic. Here, by
      employing a combination of molecular beam epitaxy and in situ angle-resolved
      photoemission spectroscopy we show that valence fluctuations can lead to dramatic
      changes in the Fermi surface topology, even resulting in a Lifshitz transition.
      As the temperature is lowered, a small electron pocket in YbAl3 becomes
      completely unoccupied while the low-energy ytterbium (Yb) 4f states become
      increasingly itinerant, acquiring additional spectral weight, longer lifetimes,
      and well-defined dispersions. Our work presents a unified picture of how local
      valence fluctuations connect to momentum-space concepts such as band filling and
      Fermi surface topology in mixed valence systems.How the electronic structure of a
      mixed-valence system changes with respect to local chemical environment remains
      elusive. Here, Chatterjee et al. show that valence fluctuations of YbAl3 can lead
      to dramatic changes in the Fermi surface topology in reciprocal space.

PMID- 29021553
TI  - Development of a Cell-Based Assay for Measuring Base Excision Repair Responses.
AB  - Base excision repair (BER) is the predominant pathway for coping with most forms
      of hydrolytic, oxidative or alkylative DNA damage. Measuring BER capacity in
      living cells is valuable for both basic science applications and epidemiological
      studies, since deficiencies in this pathway have been associated with cancer
      susceptibility and other adverse health outcomes. At present, there is an ongoing
      effort to develop methods to effectively quantify the rate of BER as a whole. We
      present a variation of a previously described "Oligonucleotide Retrieval Assay"
      designed to measure DNA excision repair that is capable of quantifying the rate
      of repair of thymine glycol in a variety of human cells with a high degree of
      sensitivity.

PMID- 29021556
TI  - Unexpected 3+ valence of iron in FeO2, a geologically important material lying
      "in between" oxides and peroxides.
AB  - Recent discovery of the pyrite FeO2, which can be an important ingredient of the
      Earth's lower mantle and which in particular may serve as an extra source of
      water in the Earth's interior, opens new perspectives for geophysics and
      geochemistry, but this is also an extremely interesting material from physical
      point of view. We found that in contrast to naive expectations Fe is nearly 3+ in
      this material, which strongly affects its magnetic properties and makes it
      qualitatively different from well known sulfide analogue - FeS2. Doping, which is
      most likely to occur in the Earth's mantle, makes FeO2 much more magnetic. In
      addition we show that unique electronic structure places FeO2 "in between" the
      usual dioxides and peroxides making this system interesting both for physics and
      solid state chemistry.

PMID- 29021555
TI  - Bypassing the Kohn-Sham equations with machine learning.
AB  - Last year, at least 30,000 scientific papers used the Kohn-Sham scheme of density
      functional theory to solve electronic structure problems in a wide variety of
      scientific fields. Machine learning holds the promise of learning the energy
      functional via examples, bypassing the need to solve the Kohn-Sham equations.
      This should yield substantial savings in computer time, allowing larger systems
      and/or longer time-scales to be tackled, but attempts to machine-learn this
      functional have been limited by the need to find its derivative. The present work
      overcomes this difficulty by directly learning the density-potential and energy
      density maps for test systems and various molecules. We perform the first
      molecular dynamics simulation with a machine-learned density functional on
      malonaldehyde and are able to capture the intramolecular proton transfer process.
      Learning density models now allows the construction of accurate density
      functionals for realistic molecular systems.Machine learning allows electronic
      structure calculations to access larger system sizes and, in dynamical
      simulations, longer time scales. Here, the authors perform such a simulation
      using a machine-learned density functional that avoids direct solution of the
      Kohn-Sham equations.

PMID- 29021554
TI  - Human TAUP301L overexpression results in TAU hyperphosphorylation without
      neurofibrillary tangles in adult zebrafish brain.
AB  - Microtubule-associated TAU protein is a pathological hallmark in Alzheimer's
      disease (AD), where hyperphosphorylation of TAU generates neurofibrillary
      tangles. To investigate the effects of TAU in a regenerative adult vertebrate
      brain system, we generated a cre/lox-based transgenic model of zebrafish that
      chronically expresses human TAUP301L, which is a variant of human TAU protein
      that forms neurofibrillary tangles in mouse models and humans. Interestingly, we
      found that although chronic and abundant expression of TAUP301L starting from
      early embryonic development led to hyperphosphorylation, TAUP301L did not form
      oligomers and neurofibrillary tangles, and did not cause elevated apoptosis and
      microglial activation, which are classical symptoms of tauopathies in mammals.
      Additionally, TAUP301L neither increased neural stem cell proliferation nor
      activated the expression of regenerative factor Interleukin-4, indicating that
      TAUP301L toxicity is prevented in the adult zebrafish brain. By combining
      TAUP301L expression with our established Abeta42 toxicity model, we found that
      Abeta42 ceases to initiate neurofibrillary tangle formation by TAUP301L, and
      TAUP301L does not exacerbate the toxicity of Abeta42. Therefore, our results
      propose a cellular mechanism that protects the adult zebrafish brain against
      tauopathies, and our model can be used to understand how TAU toxicity can be
      prevented in humans.

PMID- 29021557
TI  - Plasma-Generated OH Radical Production for Analyzing Three-Dimensional Structure
      in Protein Therapeutics.
AB  - Protein three-dimensional structure dynamically changes in solution depending on
      the presence of ligands and interacting proteins. Methods for detecting these
      changes in protein conformation include 'protein footprinting,' using mass
      spectrometry. We describe herein a new technique, PLIMB (Plasma Induced
      Modification of Biomolecules), that generates us bursts of hydroxyl radicals from
      water, to measure changes in protein structure via altered solvent accessibility
      of amino acid side chains. PLIMB was first benchmarked with model compounds, and
      then applied to a biological problem, i.e., ligand (EGF) induced changes in the
      conformation of the external (ecto) domain of Epidermal Growth Factor Receptor
      (EGFR). Regions in which oxidation decreased upon adding EGF fall along the
      dimerization interface, consistent with models derived from crystal structures.
      These results demonstrate that plasma-generated hydroxyl radicals from water can
      be used to map protein conformational changes, and provide a readily accessible
      means of studying protein structure in solution.

PMID- 29021558
TI  - Cognition in the field: comparison of reversal learning performance in captive
      and wild passerines.
AB  - Animal cognitive abilities have traditionally been studied in the lab, but
      studying cognition in nature could provide several benefits including reduced
      stress and reduced impact on life-history traits. However, it is not yet clear to
      what extent cognitive abilities can be properly measured in the wild. Here we
      present the first comparison of the cognitive performance of individuals from the
      same population, assessed using an identical test, but in contrasting contexts:
      in the wild vs. in controlled captive conditions. We show that free-ranging great
      tits (Parus major) perform similarly to deprived, captive birds in a successive
      spatial reversal-learning task using automated operant devices. In both captive
      and natural conditions, more than half of birds that contacted the device were
      able to perform at least one spatial reversal. Moreover, both captive and wild
      birds showed an improvement of performance over successive reversals, with very
      similar learning curves observed in both contexts for each reversal. Our results
      suggest that it is possible to study cognitive abilities of wild animals directly
      in their natural environment in much the same way that we study captive animals.
      Such methods open numerous possibilities to study and understand the evolution
      and ecology of cognition in natural populations.

PMID- 29021559
TI  - Identification of PTPN1 as a novel negative regulator of the JNK MAPK pathway
      using a synthetic screening for pathway-specific phosphatases.
AB  - The mitogen activated protein kinase (MAPK) signaling cascades transmit
      extracellular stimulations to generate various cellular responses via the
      sequential and reversible phosphorylation of kinases. Since the strength and
      duration of kinase phosphorylation within the pathway determine the cellular
      response, both kinases and phosphatases play an essential role in the precise
      control of MAPK pathway activation and attenuation. Thus, the identification of
      pathway-specific phosphatases is critical for understanding the functional
      mechanisms by which the MAPK pathway is regulated. To identify phosphatases
      specific to the c-Jun N-terminal kinase (JNK) MAPK pathway, a synthetic screening
      approach was utilized in which phosphatases were individually tethered to the JNK
      pathway specific-JIP1 scaffold protein. Of 77 mammalian phosphatases tested,
      PTPN1 led to the inhibition of JNK pathway activation. Further analyses revealed
      that of three pathway member kinases, PTPN1 directly dephosphorylates JNK, the
      terminal kinase of the pathway, and negatively regulates the JNK MAPK pathway.
      Specifically, PTPN1 appears to regulate the overall signaling magnitude, rather
      than the adaptation timing, suggesting that PTPN1 might be involved in the
      control and maintenance of signaling noise. Finally, the negative regulation of
      the JNK MAPK pathway by PTPN1 was found to reduce the tumor necrosis factor alpha
      (TNFalpha)-dependent cell death response.

PMID- 29021561
TI  - Ubiquitous transient stagnant domain formation during thermal convection in a
      well-mixed two component fluid with large viscosity difference.
AB  - The formation of a transient stagnant domain in the presence of thermal
      convection was previously reported near the sol-gel transition temperature of a
      gelatin solution. The transient stagnant domain is observed near a critical
      Rayleigh number where a "roll" pattern is usually stable. It is important to
      understand the origin of the transient stagnant domain formation since it induces
      a large deformation of convection patterns; the nature of the formation of the
      transient stagnant domain remains unclear. Here, we observe thermal convection
      using several different fluids and find that stagnant domain formation is
      ubiquitous in two component mixtures. In addition, we find that difference in
      viscosity between the two components is crucial for transient stagnant domain
      formation, more so than the concentration gradient induced by the temperature
      gradient.

PMID- 29021560
TI  - The thiazide sensitive sodium chloride co-transporter NCC is modulated by site
      specific ubiquitylation.
AB  - The renal sodium chloride cotransporter, NCC, in the distal convoluted tubule is
      important for maintaining body Na+ and K+ homeostasis. Endogenous NCC is highly
      ubiquitylated, but the role of individual ubiquitylation sites is not
      established. Here, we assessed the role of 10 ubiquitylation sites for NCC
      function. Transient transfections of HEK293 cells with human wildtype (WT) NCC or
      various K to R mutants identified greater membrane abundance for K706R, K828R and
      K909R mutants. Relative to WT-NCC, stable tetracycline inducible MDCKI cell lines
      expressing K706R, K828R and K909R mutants had significantly higher total and
      phosphorylated NCC levels at the apical plasma membrane under basal conditions.
      Low chloride stimulation increased membrane abundance of all mutants to similar
      or greater levels than WT-NCC. Under basal conditions K828R and K909R mutants had
      less ubiquitylated NCC in the plasma membrane, and all mutants displayed reduced
      NCC ubiquitylation following low chloride stimulation. Thiazide-sensitive sodium
      22 uptakes were elevated in the mutants and internalization from the plasma
      membrane was significantly less than WT-NCC. K909R had increased half-life,
      whereas chloroquine or MG132 treatment indicated that K706 and K909 play roles in
      lysosomal and proteasomal NCC degradation, respectively. In conclusion, site
      specific ubiquitylation of NCC plays alternative roles for NCC function.

PMID- 29021562
TI  - The sex pheromone of a globally invasive honey bee predator, the Asian eusocial
      hornet, Vespa velutina.
AB  - The Asian hornet, Vespa velutina, is an invasive, globally-distributed predator
      of European honey bees and other insects. To better under its reproductive
      biology and to find a specific, effective, and low-impact control method for this
      species, we identified and tested the key compounds in V. velutina sex pheromone.
      Virgin gynes (reproductive females) produced this sex pheromone in the sixth
      intersegmental sternal glands of their abdomens. The active compounds were 4-oxo
      octanoic acid (4-OOA, 10.4 MUg bee-1) and 4-oxo-decanoic acid (4-ODA, 13.3 MUg
      bee-1) at a 0.78 ratio of 4-OOA/4-ODA. We synthesized these compounds and showed
      that male antennae were highly sensitive to them. Moreover, males were only
      strongly attracted to a 4-OOA/4-ODA blend at the natural ratio produced by gynes.
      These results provide the first demonstration of an effective way to lure V.
      velutina males, and the first chemical identification of a sex pheromone in the
      eusocial hornets.

PMID- 29021564
TI  - Osmoprotectants, carboxymethylcellulose and hyaluronic acid multi-ingredient eye
      drop: a randomised controlled trial in moderate to severe dry eye.
AB  - This corrects the article DOI: 10.1038/eye.2017.73.

PMID- 29021565
TI  - Psychosis breakthrough on antipsychotic maintenance medication (BAMM): what can
      we learn?

PMID- 29021563
TI  - Non-canonical reader modules of BAZ1A promote recovery from DNA damage.
AB  - Members of the ISWI family of chromatin remodelers mobilize nucleosomes to
      control DNA accessibility and, in some cases, are required for recovery from DNA
      damage. However, it remains poorly understood how the non-catalytic ISWI subunits
      BAZ1A and BAZ1B might contact chromatin to direct the ATPase SMARCA5. Here, we
      find that the plant homeodomain of BAZ1A, but not that of BAZ1B, has the unusual
      function of binding DNA. Furthermore, the BAZ1A bromodomain has a non-canonical
      gatekeeper residue and binds relatively weakly to acetylated histone peptides.
      Using CRISPR-Cas9-mediated genome editing we find that BAZ1A and BAZ1B each
      recruit SMARCA5 to sites of damaged chromatin and promote survival. Genetic
      engineering of structure-designed bromodomain and plant homeodomain mutants
      reveals that reader modules of BAZ1A and BAZ1B, even when non-standard, are
      critical for DNA damage recovery in part by regulating ISWI factors loading at
      DNA lesions and supporting transcriptional programs required for survival.ISWI
      chromatin remodelers regulate DNA accessibility and have been implicated in DNA
      damage repair. Here, the authors uncover functions, in response to DNA damage,
      for the bromodomain of the ISWI subunit BAZ1B and for the non-canonical PHD and
      bromodomain modules of the paralog BAZ1A.

PMID- 29021566
TI  - High-throughput screens using photo-highlighting discover BMP signaling in
      mitochondrial lipid oxidation.
AB  - High-throughput screens at microscopic resolution can uncover molecular
      mechanisms of cellular dynamics, but remain technically challenging in live
      multicellular organisms. Here we present a genetic screening method using photo
      highlighting for candidate selection on microscopes. We apply this method to
      stimulated Raman scattering (SRS) microscopy and systematically identify 57
      Caenorhabditis elegans mutants with altered lipid distribution. Four of these
      mutants target the components of the Bone Morphogenetic Protein (BMP) signaling
      pathway, revealing that BMP signaling inactivation causes exhaustion of lipid
      reserves in somatic tissues. Using SRS-based isotope tracing assay to
      quantitatively track lipid synthesis and mobilization, we discover that the BMP
      signaling mutants have increased rates of lipid mobilization. Furthermore, this
      increase is associated with the induction of mitochondrial beta-oxidation and
      mitochondrial fusion. Together these studies demonstrate a photo-highlighting
      microscopic strategy for genome-scale screens, leading to the discovery of new
      roles for BMP signaling in linking mitochondrial homeostasis and lipid
      metabolism.High-throughput genetic screens in animals could benefit from an easy
      way to mark positive hits. Here the authors introduce photo-highlighting using a
      photoconvertible fluorescent protein, and in combination with stimulated Raman
      scattering (SRS) microscopy, define a role for BMP signaling in lipid metabolism
      in C. elegans.

PMID- 29021567
TI  - Classical swine fever virus nonstructural protein p7 modulates infectious virus
      production.
AB  - The classical swine fever virus (CSFV) nonstructural protein p7 is crucial for
      virus production, yet precisely how the p7 modulates this process is unclear. In
      this study, we first identified the interactions of p7 with E2 and NS2. The key
      binding regions of both p7 and NS2 mapped to the first transmembrane (TM1) domain
      of two proteins. Three amino acid substitutions in the TM1 region of p7
      (p7TDI18/19/20AAA, p7EVV21/22/23AAA and p7YFY25/26/30AAA) impaired infectious
      virus production and reduced the interaction of p7 with the NS2 protein. The E2p7
      processing and mature p7, but not the E2p7 precursor, are essential for
      infectious virus production. Bicistronic mutants (pSM/E2/IRES) with single
      substitutions at residues 1 to 9 of p7 exhibited a significantly increased
      infectious CSFV titer compared to their counterparts in the context of pSM. Viral
      genomic RNA copies of the mutants exhibited similar levels compared with the wt
      CSFV. Our results demonstrated that CSFV p7 and its precursor E2p7 modulate viral
      protein interactions and infectious virus production without influencing viral
      RNA replication.

PMID- 29021569
TI  - Cushioning the cartilage: a canonical Wnt restricting matter.
AB  - Wnt signalling pathways have key roles in joint development, homeostasis and
      disease, particularly in osteoarthritis. New data is starting to reveal the
      importance of tightly regulating canonical Wnt signalling pathway activation to
      maintain homeostasis and health in articular cartilage. In addition to the
      presence of different Wnt antagonists that limit pathway activation in articular
      cartilage, the reciprocal crosstalk between the canonical and non-canonical
      cascades and competitive antagonism between different Wnt ligands seem to be
      critical in restraining excessive Wnt pathway activation. Changes in
      transcriptional complex assembly upon Wnt pathway activation, epigenetic
      modulation of target gene transcription, in particular through histone
      modifications, and complex interactions between the Wnt signalling pathway and
      other signalling pathways, are also instrumental in adjusting Wnt signalling. In
      this Review, the cellular and molecular mechanisms involved in fine-tuning
      canonical Wnt signalling in the joint are updated, with a focus on the articular
      cartilage. The interventions for preventing or treating osteoarthritis are also
      discussed, which should aim to limit disease-associated excessive canonical Wnt
      activity to avoid joint damage.

PMID- 29021570
TI  - Paediatric rheumatic disease: Multi-pronged approach uncovers sJIA mechanisms.

PMID- 29021568
TI  - The brain and immune system prompt energy shortage in chronic inflammation and
      ageing.
AB  - Sequelae frequently seen in patients with chronic inflammatory diseases, such as
      fatigue, depressed mood, sleep alterations, loss of appetite, muscle wasting,
      cachectic obesity, bone loss and hypertension, can be the result of energy
      shortages caused by an overactive immune system. These sequelae can also be found
      in patients with chronic inflammatory diseases that are in remission and in
      ageing individuals, despite the immune system being less active in these
      situations. This Perspectives article proposes a new way of understanding
      situations of chronic inflammation (such as rheumatic diseases) and ageing based
      on the principles of evolutionary medicine, energy regulation and neuroendocrine
      immune crosstalk. A conceptual framework is provided to enable physicians and
      scientists to better understand the signs and symptoms of chronic inflammatory
      diseases and long-term disease consequences resulting from physical and mental
      inactivity.

PMID- 29021572
TI  - Systemic sclerosis: Antiviral drug inhibits lung fibrosis.

PMID- 29021571
TI  - Crystal arthritis: Crystallizing our ideas about gout and osteoarthritis.

PMID- 29021574
TI  - Optical cryptography with biometrics for multi-depth objects.
AB  - We propose an optical cryptosystem for encrypting images of multi-depth objects
      based on the combination of optical heterodyne technique and fingerprint keys.
      Optical heterodyning requires two optical beams to be mixed. For encryption, each
      optical beam is modulated by an optical mask containing either the fingerprint of
      the person who is sending, or receiving the image. The pair of optical masks are
      taken as the encryption keys. Subsequently, the two beams are used to scan over a
      multi-depth 3-D object to obtain an encrypted hologram. During the decryption
      process, each sectional image of the 3-D object is recovered by convolving its
      encrypted hologram (through numerical computation) with the encrypted hologram of
      a pinhole image that is positioned at the same depth as the sectional image. Our
      proposed method has three major advantages. First, the lost-key situation can be
      avoided with the use of fingerprints as the encryption keys. Second, the method
      can be applied to encrypt 3-D images for subsequent decrypted sectional images.
      Third, since optical heterodyning scanning is employed to encrypt a 3-D object,
      the optical system is incoherent, resulting in negligible amount of speckle noise
      upon decryption. To the best of our knowledge, this is the first time optical
      cryptography of 3-D object images has been demonstrated in an incoherent optical
      system with biometric keys.

PMID- 29021575
TI  - Organosulfide-plasticized solid-electrolyte interphase layer enables stable
      lithium metal anodes for long-cycle lithium-sulfur batteries.
AB  - Lithium metal is a promising anode candidate for the next-generation rechargeable
      battery due to its highest specific capacity (3860 mA h g-1) and lowest
      potential, but low Coulombic efficiency and formation of lithium dendrites hinder
      its practical application. Here, we report a self-formed flexible hybrid solid
      electrolyte interphase layer through co-deposition of
      organosulfides/organopolysulfides and inorganic lithium salts using sulfur
      containing polymers as an additive in the electrolyte. The
      organosulfides/organopolysulfides serve as "plasticizer" in the solid-electrolyte
      interphase layer to improve its mechanical flexibility and toughness. The as
      formed robust solid-electrolyte interphase layers enable dendrite-free lithium
      deposition and significantly improve Coulombic efficiency (99% over 400 cycles at
      a current density of 2 mA cm-2). A lithium-sulfur battery based on this strategy
      exhibits long cycling life (1000 cycles) and good capacity retention. This study
      reveals an avenue to effectively fabricate stable solid-electrolyte interphase
      layer for solving the issues associated with lithium metal anodes.The practical
      application of lithium metal anodes suffers from the poor Coulombic efficiency
      and growth of lithium dendrites. Here, the authors report an approach to enable
      the self-formation of stable and flexible solid-electrolyte interphase layers
      which serve to address both issues.

PMID- 29021573
TI  - An NF-kappaB-microRNA regulatory network tunes macrophage inflammatory responses.
AB  - The innate inflammatory response must be tightly regulated to ensure effective
      immune protection. NF-kappaB is a key mediator of the inflammatory response, and
      its dysregulation has been associated with immune-related malignancies. Here, we
      describe a miRNA-based regulatory network that enables precise NF-kappaB activity
      in mouse macrophages. Elevated miR-155 expression potentiates NF-kappaB activity
      in miR-146a-deficient mice, leading to both an overactive acute inflammatory
      response and chronic inflammation. Enforced miR-155 expression overrides miR-146a
      mediated repression of NF-kappaB activation, thus emphasizing the dominant
      function of miR-155 in promoting inflammation. Moreover, miR-155-deficient
      macrophages exhibit a suboptimal inflammatory response when exposed to low levels
      of inflammatory stimuli. Importantly, we demonstrate a temporal asymmetry between
      miR-155 and miR-146a expression during macrophage activation, which creates a
      combined positive and negative feedback network controlling NF-kappaB activity.
      This miRNA-based regulatory network enables a robust yet time-limited
      inflammatory response essential for functional immunity.MicroRNAs (miR) are
      important regulators of gene transcription, with miR-155 and miR-146a both
      implicated in macrophage activation. Here the authors show that NF-kappaB
      signalling, miR-155 and miR-146a form a complex network of cross-regulations to
      control gene transcription in macrophages for modulating inflammatory responses.

PMID- 29021576
TI  - The recording and characteristics of pulmonary rehabilitation in patients with
      COPD using The Health Information Network (THIN) primary care database.
AB  - : Pulmonary rehabilitation is recommended for patients with COPD to improve
      physical function, breathlessness and quality of life. Using The Health
      Information Network (THIN) primary care database in UK, we compared the
      demographic and clinical parameters of patients with COPD in relation to coding
      of pulmonary rehabilitation, and to investigate whether there is a survival
      benefit from pulmonary rehabilitation. We identified patients with COPD,
      diagnosed from 2004 and extracted information on demographics, pulmonary
      rehabilitation and clinical parameters using the relevant Read codes. Thirty six
      thousand one hundred and eighty nine patients diagnosed with COPD were included
      with a mean (SD) age of 67 (11) years, 53% were male and only 9.8% had a code
      related to either being assessed, referred, or completing pulmonary
      rehabilitation ever. Younger age at diagnosis, better socioeconomic status, worse
      dyspnoea score, current smoking, and higher comorbidities level are more likely
      to have a record of pulmonary rehabilitation. Of those with a recorded MRC of 3
      or worse, only 2057 (21%) had a code of pulmonary rehabilitation. Survival
      analysis revealed that patients with coding for pulmonary rehabilitation were 22%
      (95% CI 0.69-0.88) less likely to die than those who had no coding. In UK THIN
      records, a substantial proportion of eligible patients with COPD have not had a
      coded pulmonary rehabilitation record. Survival was improved in those with PR
      record but coding for other COPD treatments were also better in this group. GP
      practices need to improve the coding for PR to highlight any unmet need locally.
      CHRONIC LUNG DISEASE: ROLLING OUT THE REHAB: Analysis of recent UK data suggests
      that more patients with chronic lung disease could benefit from lung
      rehabilitation programmes. During pulmonary rehabilitation (PR), patients with
      chronic obstructive pulmonary disease (COPD) work with specialists to learn
      exercises and optimise breathing techniques. The programmes are recommended under
      current guidelines, particularly for patients with a high breathlessness score.
      Despite this, when Charlotte Bolton and co-workers at the University of
      Nottingham analysed 36,189 patient primary care records gathered since 2004, they
      found only 9.8% of COPD patients had ever had a coded record of being assessed,
      referred for, or undertaken PR. Those patients who completed PR were 22% less
      likely to die that those who didn't, although appeared they had also received
      better overall COPD care. Current smokers, those suffering from co-morbidities
      and younger patients were more likely to receive PR than other patient groups.

PMID- 29021577
TI  - Interleukin 17A as a good predictor of the severity of Mycoplasma pneumoniae
      pneumonia in children.
AB  - Early distinction between severe Mycoplasma pneumoniae pneumonia (MPP) and mild
      MPP is still difficult. The aim of this study was to analyze cytokines in
      bronchoalveolar lavage fluid (BALF) and explore predicting factors of severe MPP
      in children. Retrospective analysis was performed on 150 children with MPP or
      bronchial foreign body (FB) admitted in our hospital. The mRNA levels of IL17A
      were found significantly lower in severe MPP group comparing with mild MPP group
      or FB group. However, no significant difference was found in the levels of IL4,
      IL10 or interferon beta1 (IFNbeta1) between the two groups. Receiver operator
      characteristic (ROC) curve analysis showed that IL17A can be used to distinguish
      severe MPP from mild MPP. These results were confirmed in a validation cohort
      including 40 MPP children from another hospital. IL17A levels were correlated
      with some clinical characters, such as refractoriness and pleural effusion. Lower
      IL17A levels were more likely to be found in refractory MPP children or in MPP
      children with pleural effusion. Moreover, the protein levels of IL17A in BALF
      were also found greatly decreased in children with severe MPP. Thus, decreased
      IL17A levels in BALF may be a valuable biomarker to identify severe MPP in
      children.

PMID- 29021578
TI  - Strong Binding of Platelet Integrin alphaIIbbeta3 to Fibrin Clots: Potential
      Target to Destabilize Thrombi.
AB  - The formation of platelet thrombi is determined by the integrin alphaIIbbeta3
      mediated interactions of platelets with fibrinogen and fibrin. Blood clotting in
      vivo is catalyzed by thrombin, which simultaneously induces fibrinogen binding to
      alphaIIbbeta3 and converts fibrinogen to fibrin. Thus, after a short time,
      thrombus formation is governed by alphaIIbbeta3 binding to fibrin fibers.
      Surprisingly, there is little understanding of alphaIIbbeta3 interaction with
      fibrin polymers. Here we used an optical trap-based system to measure the binding
      of single alphaIIbbeta3 molecules to polymeric fibrin and compare it to
      alphaIIbbeta3 binding to monomeric fibrin and fibrinogen. Like alphaIIbbeta3
      binding to fibrinogen and monomeric fibrin, we found that alphaIIbbeta3 binding
      to polymeric fibrin can be segregated into two binding regimes, one with weaker
      rupture forces of 30-60 pN and a second with stronger rupture forces >60 pN that
      peaked at 70-80 pN. However, we found that the mechanical stability of the
      bimolecular alphaIIbbeta3-ligand complexes had the following order: fibrin
      polymer > fibrin monomer > fibrinogen. These quantitative differences reflect the
      distinct specificity and underlying molecular mechanisms of alphaIIbbeta3
      mediated reactions, implying that targeting platelet interactions with fibrin
      could increase the therapeutic indices of antithrombotic agents by focusing on
      the destabilization of thrombi rather than the prevention of platelet
      aggregation.

PMID- 29021579
TI  - Glomalin contributed more to carbon, nutrients in deeper soils, and differently
      associated with climates and soil properties in vertical profiles.
AB  - Despite vital importance in soil conditioning and a proxy for arbuscular
      mycorrhizal (AMF), glomalin-related soil protein (GRSP) contribution to soil
      carbon and nutrients at vertical soil profiles and underlying mechanism were not
      well-defined yet. Thus, 360 soil samples were collected from 72 farmland 1-m soil
      profiles in northeastern China, and soil physiochemical properties, nutrients,
      glomalin characteristics, local climates were determined. Linear decreases of
      glomalin amounts were observed from the top to deep soils, and glomalin/SOC
      (glomalin ratio to total SOC) in the 80-100 cm soil (EEG, easily-extracted GRSP,
      2.2%; TG, total GRSP, 19%) was 1.34-1.5-fold higher than did in the 0-20 cm soil.
      Different statistical analyses crosschecked that the lower pH and higher SOC
      usually accompanied with the higher EEG and TG, while EEG was more sensitive to
      climates; Moreover, glomalin was more physiochemical-regulated in the deep soils,
      but more nutrient-regulation was found in the surface soils. Structure Equation
      Model showed that soil depths and climates indirectly affected TG and EEG
      features through soil properties, except significant direct effects on EEG. In
      future, glomalin assessment should fully consider these for identifying the AMF
      importance in the whole 1-m profile, and our findings also favor degrade soil
      improvement from glomalin rehabilitation.

PMID- 29021580
TI  - The quaternary architecture of RARbeta-RXRalpha heterodimer facilitates domain
      domain signal transmission.
AB  - Assessing the physical connections and allosteric communications in multi-domain
      nuclear receptor (NR) polypeptides has remained challenging, with few crystal
      structures available to show their overall structural organizations. Here we
      report the quaternary architecture of multi-domain retinoic acid receptor beta
      retinoic X receptor alpha (RARbeta-RXRalpha) heterodimer bound to DNA, ligands
      and coactivator peptides, examined through crystallographic, hydrogen-deuterium
      exchange mass spectrometry, mutagenesis and functional studies. The RARbeta
      ligand-binding domain (LBD) and DNA-binding domain (DBD) are physically connected
      to foster allosteric signal transmission between them. Direct comparisons among
      all the multi-domain NRs studied crystallographically to date show significant
      variations within their quaternary architectures, rather than a common
      architecture adhering to strict rules. RXR remains flexible and adaptive by
      maintaining loosely organized domains, while its heterodimerization partners use
      a surface patch on their LBDs to form domain-domain interactions with
      DBDs.Nuclear receptors (NR) are multidomain proteins, which makes their
      crystallization challenging. Here the authors present the crystal structure of
      the retinoic acid receptor beta-retinoic X receptor alpha (RARbeta-RXRalpha)
      heterodimer bound to DNA, ligands and coactivator peptides, which shows that NR
      quaternary architectures are variable.

PMID- 29021581
TI  - Molecular identification of the wheat male fertility gene Ms1 and its prospects
      for hybrid breeding.
AB  - The current rate of yield gain in crops is insufficient to meet the predicted
      demands. Capturing the yield boost from heterosis is one of the few technologies
      that offers rapid gain. Hybrids are widely used for cereals, maize and rice, but
      it has been a challenge to develop a viable hybrid system for bread wheat due to
      the wheat genome complexity, which is both large and hexaploid. Wheat is our most
      widely grown crop providing 20% of the calories for humans. Here, we describe the
      identification of Ms1, a gene proposed for use in large-scale, low-cost
      production of male-sterile (ms) female lines necessary for hybrid wheat seed
      production. We show that Ms1 completely restores fertility to ms1d, and encodes a
      glycosylphosphatidylinositol-anchored lipid transfer protein, necessary for
      pollen exine development. This represents a key step towards developing a robust
      hybridization platform in wheat.Heterosis can rapidly boost yield in crop species
      but development of hybrid-breeding systems for bread wheat remains a challenge.
      Here, Tucker et al. describe the molecular identification of the wheat Ms1 gene
      and discuss its potential for large-scale hybrid seed production in wheat.

PMID- 29021582
TI  - Novel mechanism of regulation of the 5-lipoxygenase/leukotriene B4 pathway by
      high-density lipoprotein in macrophages.
AB  - High-density lipoprotein (HDL) interacts with various cells, particularly
      macrophages, in functional cell-HDL interactions. Here, we found that HDL protein
      quality and lipid quality play critical roles in HDL functions. HDL fractions
      from healthy volunteers (HDLHealthy) and patients with recurrent coronary
      atherosclerotic disease (HDLCAD) were prepared. To analyse functional HDL
      macrophage interactions, macrophages were co-incubated with each HDL, and lipid
      mediator production was assessed by liquid chromatography/mass spectrometry-based
      metabololipidomics. HDLHealthy treatment attenuated the pro-inflammatory lipid
      mediator production, particularly that of leukotriene (LT) B4, and this treatment
      enhanced lipoxin (LX) B4 and resolvin (Rv) E2 production. HDLHealthy treatment
      enhanced the proteasome-mediated degradation of the LTB4-producing enzyme 5
      lipoxygenase (LO) in activated macrophages; however, HDLCAD did not show these
      anti-inflammatory effects. HDLHealthy was engulfed by macrophages via clathrin
      mediated endocytosis, which was a critical step in 5-LO/LTB4 regulation. We also
      found that HDLCAD showed higher levels of the LTB4-producing enzymes and thus
      promoted LTB4 production from HDLCAD. In addition, LTB4 attenuated HDL
      endocytosis, HDL-mediated 5-LO degradation in macrophages, and HDL-derived
      augmentation of macrophage phagocytosis. These results indicated that local LTB4
      produced de novo from HDLCAD regulates HDL-macrophage functional interactions and
      plays critical roles in dysfunctional, inflammatory HDL characteristics.

PMID- 29021583
TI  - Polydopamine-Laced Biomimetic Material Stimulation of Bone Marrow Derived
      Mesenchymal Stem Cells to Promote Osteogenic Effects.
AB  - A hydroxyapatite-collagen (HC) composite material can mimic composition and ultra
      structures of natural bone and provide adequate bioactive material-tissue
      interactions. Incorporation of dopamine (DA) is one of keys in increasing the
      mechanical strength of the HC material to approaching that of cortical bone. In
      this study, the in vitro osteogenic effects of polydopamine-laced hydroxyapatite
      collagen calcium silicate (HCCS-PDA) were examined by culturing rat mesenchymal
      stem cells (rMSCs) on HCCS-PDA and HCCS coated plates. HCCS-PDA group
      demonstrated less cytotoxic from Live/Dead cytotoxic assay and displayed higher
      cell attachment, proliferation and mineralization than the HCCS group in vitro.
      For in vivo bone regeneration, HCCS-PDA or HCCS particulates with or without rMSC
      aggregates were implanted into rat critical-sized calvarial defects (CSD). After
      12 weeks, calvarial bone regeneration was evaluated radiographically,
      histologically, and histomorphometrically. While the majority of new bone
      formation occurred around the HCCS-PDA particulates with rMSC aggregates, The
      HCCS-PDA particulates without rMSC aggregates showed limited osteoconductivity.
      HCCS with or without rMSC aggregates resulted in less bone formation, indicating
      a prominent role of DA in effective bone regeneration. Therefore, the HCCS-PDA
      biomaterial with the aid of rMSCs can be used to develop therapeutic strategies
      in bone tissue engineering with numerable clinical applications.

PMID- 29021584
TI  - Mortalin deficiency suppresses fibrosis and induces apoptosis in keloid
      spheroids.
AB  - Mortalin (Mot) is a mitochondrial chaperone of the heat shock protein 70 family
      and it's pro-proliferative and anti-apoptosis functions could be associated with
      keloid pathogenesis, and blocking of mortalin and its interaction with p53 might
      be a potential novel target for the treatment of keloid. Therefore, we generated
      mortalin-specific small hairpin (sh) RNAs (dE1-RGD/GFP/shMot) and introduced into
      keloid spheroids for examination of its apoptotic and anti-fibrotic effect. On
      keloid tissues, mortalin expression was higher than adjacent normal tissues and
      it's protein expressions were activated keloid fibroblasts (KFs). After primary
      keloid spheroid were transduced with dE1-RGD/GFP/shMot for knockdown of mortalin,
      expression of type I, III collagen, fibronectin, and elastin was significantly
      reduced and transforming growth factor-beta1, epidermal growth factor receptor
      (EGFR), Extracellular Signal-Regulated Kinases 1 and 2 (Erk 1/2), and Smad 2/3
      complex protein expression were decreased. In addition, increased TUNEL
      activities and cytochrome C were observed. Further, for examine of mortalin and
      p53 interaction, we performed immunofluorescence analysis. Knockdown of mortalin
      relocated p53 to the cell nucleus in primary keloid spheroids by dE1
      RGD/GFP/shMot transduction. These results support the utility of knockdown of
      mortalin to induce apoptosis and reduce ECMs expression in keloid spheroid, which
      may be highly beneficial in treating keloids.

PMID- 29021585
TI  - Perceived stress level and risk of cancer incidence in a Japanese population: the
      Japan Public Health Center (JPHC)-based Prospective Study.
AB  - Evidence regarding stress as a risk factor for cancer onset is inconsistent. In
      this study, based on the Japan Public Health Center-based Prospective Study, we
      enrolled 101,708 participants aged 40-69 years from 1990-1994. The self-reported
      perceived stress level was collected at baseline and updated through 5-year
      follow-up. The association between perceived stress and cancer risk was measured
      by Cox proportional hazards regression model, adjusted for all known confounders.
      During follow-up (mean = 17.8 years), we identified 17,161 cancer cases. We found
      no association between baseline perceived stress level and cancer incidence.
      However, by taking account of the dynamic changes in perceived stress, time
      varying analyses revealed a slightly (4-6%) increased overall cancer risk for
      subjects under elevated perceived stress levels compared to the 'low stress
      level' group. Analyses concerning long-term perceived stress level showed that
      individuals with constantly high perceived stress level had an 11% (95%
      confidence interval 1-22%) excess risk for cancer compared to subjects with
      persistently low stress levels. This association was confined to men (20% excess
      risk), and was particularly strong among smokers, alcohol drinkers, obese
      subjects, and subjects without family history of cancer. Therefore, we concluded
      high perceived stress level might contribute to excess overall cancer incidence
      among men.

PMID- 29021586
TI  - Colloidal Force Study of Particle Fouling on Gas Capture Membrane.
AB  - Membrane fouling induced by industrial flue gas deteriorates their gas capturing
      efficiency, which is mainly caused by the adhesion of aerosol particles. To fully
      understand the mechanism of membrane fouling, a quantitative study of the
      adhesion force of particle on membrane surface was investigated by atomic force
      microscopy (AFM). The adhesion force of a single particle with flat glass,
      silicon wafer, PP (polypropylene) membrane, and fly-ash particles were measured
      within the relative humidity (RH) of 0 ~ 85%. The results showed the adhesion
      force of a particle with membrane have not much difference from the glass and
      silica wafer. And the surface roughness of flat substrate has slight effect on
      the adhesion force of the micrometer scale particle on flat surface at dry
      condition, while measured adhesion forces show obvious RH dependent for glass and
      membrane. Additionally, at dry conditions, the adhesion force of inter-particles
      also shows no obvious quantitative difference but obvious scattering comparing to
      that on membrane. The adhesion force of inter-particles increased more higher
      with the RH than that on membrane, which indicates the adhesion between
      micrometer scale particles can accelerate the deposition of particles on membrane
      and contributes the most to membrane fouling in industry atmosphere.

PMID- 29021588
TI  - Robust Fusion of Diffusion MRI Data for Template Construction.
AB  - Construction of brain templates is generally carried out using a two-step
      procedure involving registering a population of images to a common space and then
      fusing the aligned images to form a template. In practice, image registration is
      not perfect and simple averaging of the images will blur structures and cause
      artifacts. In diffusion MRI, this is further complicated by intra-voxel inter
      subject differences in fiber orientation, fiber configuration, anisotropy, and
      diffusivity. In this paper, we propose a method to improve the construction of
      diffusion MRI templates in light of inter-subject differences. Our method
      involves a novel q-space (i.e., wavevector space) patch matching mechanism that
      is incorporated in a mean shift algorithm to seek the most probable signal at
      each point in q-space. Our method relies on the fact that the mean shift
      algorithm is a mode seeking algorithm that converges to the mode of a
      distribution and is hence robust to outliers. Our method is therefore in effect
      seeking the most probable signal profile at each voxel given a distribution of
      signal profiles. Experimental results show that our method yields diffusion MRI
      templates with cleaner fiber orientations and less artifacts caused by inter
      subject differences in fiber orientation.

PMID- 29021587
TI  - Relationships between structure, in vivo function and long-range axonal target of
      cortical pyramidal tract neurons.
AB  - Pyramidal tract neurons (PTs) represent the major output cell type of the
      neocortex. To investigate principles of how the results of cortical processing
      are broadcasted to different downstream targets thus requires experimental
      approaches, which provide access to the in vivo electrophysiology of PTs, whose
      subcortical target regions are identified. On the example of rat barrel cortex
      (vS1), we illustrate that retrograde tracer injections into multiple subcortical
      structures allow identifying the long-range axonal targets of individual in vivo
      recorded PTs. Here we report that soma depth and dendritic path lengths within
      each cortical layer of vS1, as well as spiking patterns during both periods of
      ongoing activity and during sensory stimulation, reflect the respective
      subcortical target regions of PTs. We show that these cellular properties result
      in a structure-function parameter space that allows predicting a PT's subcortical
      target region, without the need to inject multiple retrograde tracers.The major
      output cell type of the neocortex - pyramidal tract neurons (PTs) - send axonal
      projections to various subcortical areas. Here the authors combined in vivo
      recordings, retrograde tracings, and reconstructions of PTs in rat somatosensory
      cortex to show that PT structure and activity can predict specific subcortical
      targets.

PMID- 29021589
TI  - Enhanced cell attachment and hemocompatibility of titanium by nanoscale surface
      modification through severe plastic integration of magnesium-rich islands and
      porosification.
AB  - Besides the wide applications of titanium and its alloys for orthopedic and
      biomedical implants, the biocompatible nature of titanium has emerged various
      surface modification techniques to enhance its bioactivity and osteointegration
      with living tissues. In this work, we present a new procedure for nanoscale
      surface modification of titanium implants by integration of magnesium-rich
      islands combined with controlled formation of pores and refinement of the surface
      grain structure. Through severe plastic deformation of the titanium surface with
      fine magnesium hydride powder, Mg-rich islands with varying sizes ranging from
      100 nm to 1000 nm can be integrated inside a thin surface layer (100-500 um) of
      the implant. Selective etching of the surface forms a fine structure of surface
      pores which their average size varies in the range of 200-500 nm depending on the
      processing condition. In vitro biocompatibility and hemocompatibility assays show
      that the Mg-rich islands and the induced surface pores significantly enhance cell
      attachment and biocompatibility without an adverse effect on the cell viability.
      Therefore, severe plastic integration of Mg-rich islands on titanium surface
      accompanying with porosification is a new and promising procedure with high
      potential for nanoscale modification of biomedical implants.

PMID- 29021590
TI  - Influence of adaptive capacity on the outcome of climate change vulnerability
      assessment.
AB  - Climate change vulnerability assessment (CCVA) has become a mainstay conservation
      decision support tool. CCVAs are recommended to incorporate three elements of
      vulnerability - exposure, sensitivity and adaptive capacity - yet, lack of data
      frequently leads to the latter being excluded. Further, weighted or unweighted
      scoring schemes, based on expert opinion, may be applied. Comparisons of these
      approaches are rare. In a CCVA for 17 Australian lizard species, we show that
      membership within three vulnerability categories (low, medium and high) generally
      remained similar regardless of the framework or scoring scheme. There was one
      exception however, where, under the warm/dry scenario for 2070, including
      adaptive capacity lead to five fewer species being classified as highly
      vulnerable. Two species, Eulamprus leuraensis and E. kosciuskoi, were
      consistently ranked the most vulnerable, primarily due to projected losses in
      climatically suitable habitat, narrow thermal tolerance and specialist habitat
      requirements. Our findings provide relevant information for prioritizing target
      species for conservation and choosing appropriate conservation actions. We
      conclude that for the species included in this study, the framework and scoring
      scheme used had little impact on the identification of the most vulnerable
      species. We caution, however, that this outcome may not apply to other taxa or
      regions.

PMID- 29021591
TI  - Highly sensitive, self-powered and wearable electronic skin based on pressure
      sensitive nanofiber woven fabric sensor.
AB  - The wearable electronic skin with high sensitivity and self-power has shown
      increasing prospects for applications such as human health monitoring, robotic
      skin, and intelligent electronic products. In this work, we introduced and
      demonstrated a design of highly sensitive, self-powered, and wearable electronic
      skin based on a pressure-sensitive nanofiber woven fabric sensor fabricated by
      weaving PVDF electrospun yarns of nanofibers coated with PEDOT. Particularly, the
      nanofiber woven fabric sensor with multi-leveled hierarchical structure, which
      significantly induced the change in contact area under ultra-low load, showed
      combined superiority of high sensitivity (18.376 kPa-1, at ~100 Pa), wide
      pressure range (0.002-10 kPa), fast response time (15 ms) and better durability
      (7500 cycles). More importantly, an open-circuit voltage signal of the PPNWF
      pressure sensor was obtained through applying periodic pressure of 10 kPa, and
      the output open-circuit voltage exhibited a distinct switching behavior to the
      applied pressure, indicating the wearable nanofiber woven fabric sensor could be
      self-powered under an applied pressure. Furthermore, we demonstrated the
      potential application of this wearable nanofiber woven fabric sensor in
      electronic skin for health monitoring, human motion detection, and muscle tremor
      detection.

PMID- 29021592
TI  - A turn-on endoplasmic reticulum-targeted two-photon fluorescent probe for
      hydrogen sulfide and bio-imaging applications in living cells, tissues, and
      zebrafish.
AB  - As one of the important gas signal molecules, hydrogen sulfide (H2S) is
      associated with many important physiological processes in living organisms.
      Organelles, especially endoplasmic reticulum (ER), play a crucial role in the
      cell metabolism. Accordingly, the detection of H2S in the ER is of high interest.
      Toward this goal, we have described the development of the first ER-targeted
      fluorescent H2S probe (Na-H 2 S-ER). The new probe exhibited favorable features,
      such as a large turn-on fluorescence signal (45-fold fluorescence enhancement),
      high sensitivity and selectivity. The probe was successfully employed for imaging
      exogenous and endogenous H2S in the living HeLa cells. Significantly, the new
      probe Na-H 2 S-ER was employed to visualize H2S in the ER of living cells for the
      first time. In addition, the probe was also successfully used for imaging H2S in
      the living tissues up to a depth of 100 MUm and in the living zebrafish.

PMID- 29021594
TI  - Understanding drug resistance will improve the treatment of bacterial infections.

PMID- 29021593
TI  - A coordinated sequence of distinct flagellar waveforms enables a sharp flagellar
      turn mediated by squid sperm pH-taxis.
AB  - Animal spermatozoa navigate by sensing ambient chemicals to reach the site of
      fertilization. Generally, such chemicals derive from the female reproductive
      organs or cells. Exceptionally, squid spermatozoa mutually release and perceive
      carbon dioxide to form clusters after ejaculation. We previously identified the
      pH-taxis by which each spermatozoon can execute a sharp turn, but how flagellar
      dynamics enable this movement remains unknown. Here, we show that initiation of
      the turn motion requires a swim down a steep proton gradient (a theoretical
      estimation of >=0.025 pH/s), crossing a threshold pH value of ~5.5. Time-resolved
      kinematic analysis revealed that the turn sequence results from the rhythmic
      exercise of two flagellar motions: a stereotypical flagellar 'bent-cane' shape
      followed by asymmetric wave propagation, which enables a sharp turn in the realm
      of low Reynolds numbers. This turning episode is terminated by an 'overshoot'
      trajectory that differs from either straight-line motility or turning. As with
      bidirectional pH-taxes in some bacteria, squid spermatozoa also showed repulsion
      from strong acid conditions with similar flagellar kinematics as in positive pH
      taxis. These findings indicate that squid spermatozoa might have a unique
      reorientation mechanism, which could be dissimilar to that of classical egg
      guided sperm chemotaxis in other marine invertebrates.

PMID- 29021595
TI  - Carpe diet.

PMID- 29021596
TI  - Microbiome: Diving deeper into the communities.

PMID- 29021597
TI  - Bacterial pathogenesis: It takes two to tango.

PMID- 29021599
TI  - Viral infection: Adapt or get zapped.

PMID- 29021601
TI  - Novel vaccine vectors for HIV-1.

PMID- 29021600
TI  - Diagnosing antimicrobial resistance.
AB  - Antimicrobial resistance constitutes a global burden and is one of the major
      threats to public health. Although the emergence of resistant microorganisms is a
      natural phenomenon, the overuse or inappropriate use of antimicrobials has had a
      great effect on resistance evolution. Rapid diagnostic tests that identify drug
      resistant bacteria, determine antimicrobial susceptibility and distinguish viral
      from bacterial infections can guide effective treatment strategies. Moreover,
      rapid diagnostic tests could facilitate epidemiological surveillance, as emerging
      resistant infectious agents and transmission can be monitored. In this Viewpoint
      article, several experts in the field discuss the drawbacks of current diagnostic
      methods that are used to identify antimicrobial resistance, novel diagnostic
      strategies and how such rapid tests can inform drug development and the
      surveillance of resistance evolution.

PMID- 29021602
TI  - Biofilms: The architect of the biofilm.

PMID- 29021603
TI  - Bacterial physiology: Making a memory.

PMID- 29021604
TI  - Fungal physiology: Two for the price of one.

PMID- 29021598
TI  - The commensal lifestyle of Staphylococcus aureus and its interactions with the
      nasal microbiota.
AB  - Although human colonization by facultative bacterial pathogens, such as
      Staphylococcus aureus, represents a major risk factor for invasive infections,
      the commensal lifestyle of such pathogens has remained a neglected area of
      research. S. aureus colonizes the nares of approximately 30% of the human
      population and recent studies suggest that the composition of highly variable
      nasal microbiota has a major role in promoting or inhibiting S. aureus
      colonization. Competition for epithelial attachment sites or limited nutrients,
      different susceptibilities to host defence molecules and the production of
      antimicrobial molecules may determine whether nasal bacteria outcompete each
      other. In this Review, we discuss recent insights into mechanisms that are used
      by S. aureus to prevail in the human nose and the counter-strategies that are
      used by other nasal bacteria to interfere with its colonization. Understanding
      such mechanisms will be crucial for the development of new strategies for the
      eradication of endogenous facultative pathogens.

PMID- 29021605
TI  - A large predatory reef fish species moderates feeding and activity patterns in
      response to seasonal and latitudinal temperature variation.
AB  - Climate-driven increases in ocean temperatures are expected to affect the
      metabolic requirements of marine species substantially. To mitigate the impacts
      of increasing temperatures in the short-term, it may be necessary for ectothermic
      organisms to alter their foraging behaviour and activity. Herein, we investigate
      seasonal variation in foraging behaviour and activity of latitudinally distinct
      populations of a large coral reef predator, the common coral trout, Plectropomus
      leopardus, from the Great Barrier Reef, Australia. P. leopardus exhibited
      increased foraging frequency in summer versus winter time, irrespective of
      latitude, however, foraging frequency substantially declined at water
      temperatures >30  degrees C. Foraging frequency also decreased with body size but
      there was no interaction with temperature. Activity patterns were directly
      correlated with water temperature; during summer, the low-latitude population of
      P. leopardus spent up to 62% of their time inactive, compared with 43% for the
      high-latitude population. The impact of water temperature on activity patterns
      was greatest for larger individuals. These results show that P. leopardus
      moderate their foraging behaviour and activity according to changes in ambient
      temperatures. It seems likely that increasing ocean temperatures may impose
      significant constraints on the capacity of large-bodied fishes to obtain
      sufficient prey resources while simultaneously conserving energy.

PMID- 29021606
TI  - Higher Expression of Toll-Like Receptors 2 and 4 in Blood Cells of Keratoconus
      Patiens.
AB  - Inflammation may play a significant role in Keratoconus (KC), but the implication
      of immunity on this inflammatory response is unknown. Therefore, our aim was to
      determine the expression levels of Toll-like receptors 2 (TLR2) and 4 (TLR4) in
      monocytes and neutrophils from patients with KC and control subjects for
      demonstrating the role of innate immunity in KC. We also study the correlation
      between TLR2/TLR4 expression and serum levels of proinflammatory markers (IL
      1beta, IL-6, TNF-alpha, MMP-9 and NF-kappaB). Forty patients with bilateral KC
      (55% males; mean age; 33.1 +/- 10.9 years) and 20 control subjects (55% males;
      mean age; 30.4 +/- 7.6 years) were included in the study. Our results showed that
      mean expression of TLR2 and TLR4 in both neutrophils and monocytes was
      significantly higher in patients with KC compared to control subjects (all p <
      0.0001). Furthermore, KC patients also showed higher serum levels of IL-1B, IL-6,
      TNF-alpha, MMP-9 (all p < 0.0001) and NF-kappaB (p = 0.036). In addition, we
      found a strong correlation between TLR2 expression in both monocytes and
      neutrophils (all p < 0.0001), and TLR4 in monocytes (all p < 0.05) with serum
      levels of IL-1B, IL-6, TNF-alpha and MMP-9. In conclusion, these findings suggest
      that TLRs may play an important role in the pathophysiology of KC.

PMID- 29021607
TI  - Turnover and flow of the cell membrane for cell migration.
AB  - The role of cell membrane dynamics in cell migration is unclear. To examine
      whether total cell surface area changes are required for cell migration,
      Dictyostelium cells were flattened by agar-overlay. Scanning electron microscopy
      demonstrated that flattened migrating cells have no membrane reservoirs such as
      projections and membrane folds. Similarly, optical sectioning fluorescence
      microscopy showed that the cell surface area does not change during migration.
      Interestingly, staining of the cell membrane with a fluorescent lipid analogue
      demonstrated that the turnover rate of cell membrane is closely related to the
      cell migration velocity. Next, to clarify the mechanism of cell membrane
      circulation, local photobleaching was separately performed on the dorsal and
      ventral cell membranes of rapidly moving cells. The bleached zones on both sides
      moved rearward relative to the cell. Thus, the cell membrane moves in a fountain
      like fashion, accompanied by a high membrane turnover rate and actively
      contributing to cell migration.

PMID- 29021608
TI  - Amyloidogenic motifs revealed by n-gram analysis.
AB  - Amyloids are proteins associated with several clinical disorders, including
      Alzheimer's, and Creutzfeldt-Jakob's. Despite their diversity, all amyloid
      proteins can undergo aggregation initiated by short segments called hot spots. To
      find the patterns defining the hot spots, we trained predictors of
      amyloidogenicity, using n-grams and random forest classifiers. Since the
      amyloidogenicity may not depend on the exact sequence of amino acids but on their
      more general properties, we tested 524,284 reduced amino acid alphabets of
      different lengths (three to six letters) to find the alphabet providing the best
      performance in cross-validation. The predictor based on this alphabet, called
      AmyloGram, was benchmarked against the most popular tools for the detection of
      amyloid peptides using an external data set and obtained the highest values of
      performance measures (AUC: 0.90, MCC: 0.63). Our results showed sequential
      patterns in the amyloids which are strongly correlated with hydrophobicity, a
      tendency to form beta-sheets, and lower flexibility of amino acid residues. Among
      the most informative n-grams of AmyloGram we identified 15 that were previously
      confirmed experimentally. AmyloGram is available as the web-server:
      http://smorfland.uni.wroc.pl/shiny/AmyloGram/ and as the R package AmyloGram. R
      scripts and data used to produce the results of this manuscript are available at
      http://github.com/michbur/AmyloGramAnalysis .

PMID- 29021609
TI  - A cdk1 gradient guides surface contraction waves in oocytes.
AB  - Surface contraction waves (SCWs) in oocytes and embryos lead to large-scale shape
      changes coupled to cell cycle transitions and are spatially coordinated with the
      cell axis. Here, we show that SCWs in the starfish oocyte are generated by a
      traveling band of myosin II-driven cortical contractility. At the front of the
      band, contractility is activated by removal of cdk1 inhibition of the RhoA/RhoA
      kinase/myosin II signaling module, while at the rear, contractility is switched
      off by negative feedback originating downstream of RhoA kinase. The SCW's
      directionality and speed are controlled by a spatiotemporal gradient of cdk1
      cyclinB. This gradient is formed by the release of cdk1-cyclinB from the
      asymmetrically located nucleus, and progressive degradation of cyclinB. By
      combining quantitative imaging, biochemical and mechanical perturbations with
      mathematical modeling, we demonstrate that the SCWs result from the
      spatiotemporal integration of two conserved regulatory modules, cdk1-cyclinB for
      cell cycle regulation and RhoA/Rok/NMYII for actomyosin contractility.Surface
      contraction waves (SCWs) are prominent shape changes coupled to cell cycle
      transitions in oocytes. Here the authors show that SCWs are patterned by the
      spatiotemporal integration of two conserved modules, cdk1-cyclinB for cell cycle
      regulation and RhoA/Rok/NMYII for actomyosin contractility.

PMID- 29021610
TI  - Low immunogenicity of mouse induced pluripotent stem cell-derived neural
      stem/progenitor cells.
AB  - Resolving the immunogenicity of cells derived from induced pluripotent stem cells
      (iPSCs) remains an important challenge for cell transplant strategies that use
      banked allogeneic cells. Thus, we evaluated the immunogenicity of mouse fetal
      neural stem/progenitor cells (fetus-NSPCs) and iPSC-derived neural
      stem/progenitor cells (iPSC-NSPCs) both in vitro and in vivo. Flow cytometry
      revealed the low expression of immunological surface antigens, and these cells
      survived in all mice when transplanted syngeneically into subcutaneous tissue and
      the spinal cord. In contrast, an allogeneic transplantation into subcutaneous
      tissue was rejected in all mice, and allogeneic cells transplanted into intact
      and injured spinal cords survived for 3 months in approximately 20% of mice. In
      addition, cell survival was increased after co-treatment with an
      immunosuppressive agent. Thus, the immunogenicity and post-transplantation
      immunological dynamics of iPSC-NSPCs resemble those of fetus-NSPCs.

PMID- 29021611
TI  - Spatial detection of fetal marker genes expressed at low level in adult human
      heart tissue.
AB  - Heart failure is a major health problem linked to poor quality of life and high
      mortality rates. Hence, novel biomarkers, such as fetal marker genes with low
      expression levels, could potentially differentiate disease states in order to
      improve therapy. In many studies on heart failure, cardiac biopsies have been
      analyzed as uniform pieces of tissue with bulk techniques, but this
      homogenization approach can mask medically relevant phenotypes occurring only in
      isolated parts of the tissue. This study examines such spatial variations within
      and between regions of cardiac biopsies. In contrast to standard RNA sequencing,
      this approach provides a spatially resolved transcriptome- and tissue-wide
      perspective of the adult human heart, and enables detection of fetal marker genes
      expressed by minor subpopulations of cells within the tissue. Analysis of
      patients with heart failure, with preserved ejection fraction, demonstrated
      spatially divergent expression of fetal genes in cardiac biopsies.

PMID- 29021612
TI  - IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFalpha
      on myotube development.
AB  - Studies in murine cell lines and in mouse models suggest that IL-15 promotes
      myogenesis and may protect against the inflammation-mediated skeletal muscle
      atrophy which occurs in sarcopenia and cachexia. The effects of IL-15 on human
      skeletal muscle growth and development remain largely uncharacterised. Myogenic
      cultures were isolated from the skeletal muscle of young and elderly subjects.
      Myoblasts were differentiated for 8 d, with or without the addition of
      recombinant cytokines (rIL-15, rTNFalpha) and an IL-15 receptor neutralising
      antibody. Although myotubes were 19% thinner in cultures derived from elderly
      subjects, rIL-15 increased the thickness of myotubes (MTT) from both age groups
      to a similar extent. Neutralisation of the high-affinity IL-15 receptor binding
      subunit, IL-15ralpha in elderly myotubes confirmed that autocrine concentrations
      of IL-15 also support myogenesis. Co-incubation of differentiating myoblasts with
      rIL-15 and rTNFalpha, limited the reduction in MTT and nuclear fusion index (NFI)
      associated with rTNFalpha stimulation alone. IL-15ralpha neutralisation and
      rTNFalpha decreased MTT and NFI further. This, coupled with our observation that
      myotubes secrete IL-15 in response to TNFalpha stimulation supports the notion
      that IL-15 serves to mitigate inflammatory skeletal muscle loss. IL-15 may be an
      effective therapeutic target for the attenuation of inflammation-mediated
      skeletal muscle atrophy.

PMID- 29021613
TI  - Uncoupling Oncogene-Induced Senescence (OIS) and DNA Damage Response (DDR)
      triggered by DNA hyper-replication: lessons from primary mouse embryo astrocytes
      (MEA).
AB  - Oncogene-induced senescence (OIS) is a complex process, in which activation of
      oncogenic signals during early tumorigenesis results in a high degree of DNA
      replication stress. The ensuing response to the DNA damage produces a permanent
      G1 arrest that prevents unlimited cell proliferation and lessens the development
      of tumours. However, despite the role of OIS in the proliferative arrest
      resulting from an activating oncogenic-lesion has obtained wide support, there is
      also evidence indicating that cells may overcome oncogene-induced senescence
      under some circumstances. In this study, we have investigated the possibility
      that some of the assumptions on the role of DNA damage response (DDR) in
      triggering OIS may depend on the fact that most of the available data were
      obtained in mouse embryo fibroblast. By comparing the degree of OIS observed in
      mouse embryo fibroblasts (MEF) and mouse embryo astrocytes (MEA) obtained from
      the same individuals we have demonstrated that, despite truthful activation of
      DDR in both cell types, significant levels of OIS were only detected in MEF.
      Therefore, this uncoupling between OIS and DDR observed in astrocytes supports
      the intriguingly possibility that OIS is not a widespread response mechanism to
      DDR.

PMID- 29021614
TI  - Digital nonlinearity compensation in high-capacity optical communication systems
      considering signal spectral broadening effect.
AB  - Nyquist-spaced transmission and digital signal processing have proved effective
      in maximising the spectral efficiency and reach of optical communication systems.
      In these systems, Kerr nonlinearity determines the performance limits, and leads
      to spectral broadening of the signals propagating in the fibre. Although digital
      nonlinearity compensation was validated to be promising for mitigating Kerr
      nonlinearities, the impact of spectral broadening on nonlinearity compensation
      has never been quantified. In this paper, the performance of multi-channel
      digital back-propagation (MC-DBP) for compensating fibre nonlinearities in
      Nyquist-spaced optical communication systems is investigated, when the effect of
      signal spectral broadening is considered. It is found that accounting for the
      spectral broadening effect is crucial for achieving the best performance of DBP
      in both single-channel and multi-channel communication systems, independent of
      modulation formats used. For multi-channel systems, the degradation of DBP
      performance due to neglecting the spectral broadening effect in the compensation
      is more significant for outer channels. Our work also quantified the minimum
      bandwidths of optical receivers and signal processing devices to ensure the
      optimal compensation of deterministic nonlinear distortions.

PMID- 29021616
TI  - The thermogenic actions of natriuretic peptide in brown adipocytes: The direct
      measurement of the intracellular temperature using a fluorescent thermoprobe.
AB  - In addition to the various effects of natriuretic peptides (NPs) on
      cardiovascular systems, increasing attention is being paid to the possibility
      that NPs induce adipose tissue browning and activate thermogenic program. We
      herein established a direct intracellular temperature measurement system using a
      fluorescent thermoprobe and investigated the thermogenic effects of A-type NP
      (ANP) on brown adipocytes. The thermoprobe was successfully introduced into rat
      brown adipocytes, and the temperature dependent change in fluorescence intensity
      ratio was measured using a fluorescence microscope. After one-hour incubation
      with ANP, the degree of the change in fluorescence intensity ratio was
      significantly higher in ANP-treated (P < 0.01) adipocytes compared to untreated
      controls. The ANP treatment increased uncoupling protein-1 (UCP1) mRNA levels,
      which is one of the markers of thermogenesis in adipocytes, while the
      intracellular ATP content was not changed, indicating mitochondrial uncoupled
      respiration. Intriguingly, these thermogenic actions of ANP were more prominent
      when brown adipocytes were incubated at 35  degrees C than at 37  degrees C.
      Moreover, the increase in the intracellular temperature and the expression of
      UCP1 induced by ANP were cancelled by p38MAPK inhibition. Taken together, this
      study directly demonstrated the thermogenic actions of ANP in brown adipocytes
      through the use of a novel method of intracellular temperature measurement.

PMID- 29021617
TI  - Imaging mass spectrometry analysis of ubiquinol localization in the mouse brain
      following short-term administration.
AB  - We analyzed the localization of ubiquinol, the reduced form of coenzyme Q10 (Re
      CoQ10), in mouse brain sections using matrix-assisted laser desorption/ionization
      Fourier transform ion cyclotron resonance imaging mass spectrometry (IMS) to
      evaluate the effect of dietary Re-CoQ10 in mouse brain. Mice were orally
      administered Re-CoQ10 for 14 days and brain Re-CoQ10 content was subsequently
      quantified using liquid chromatography-mass spectrometry. IMS was employed to
      visualize Re-CoQ10 at a resolution of 150 MUm in the mouse brain. Increased Re
      CoQ10 was observed in the corpus callosum, hippocampus, midbrain, cerebellum,
      brain stem, substantia nigra and striatum. These regions are related to movement,
      memory and vital life functions. Thus, we demonstrated the effect of Re-CoQ10
      administration on the specific localization of Re-CoQ10 in the brain.

PMID- 29021615
TI  - A New Pedicled Internal Mammary Osteomyocutaneous Chimeric Flap (PIMOC) for
      Salvage Head and Neck Reconstruction: Anatomic Study and Clinical Application.
AB  - Well-vascularized composite tissue offers improved outcomes for complex head and
      neck reconstruction. Patients with vessel-depleted necks and failed
      reconstructions require alternative reconstructive options. We describe a
      pedicled internal mammary artery osteomyocutaneous chimeric flap (PIMOC) for
      salvage head and neck reconstruction. Bilateral dissections of 35 fresh cadavers
      were performed to study individual tissue components and vascular pedicles to
      develop the PIMOC technique. The flap was then utilized in a series of patients
      with vessel-depleted neck anatomy. The PIMOC was dissected bilaterally in all
      cadavers and there were no statistical differences in vascular pedicle caliber or
      length with regards to laterality or gender. Five patients subsequently underwent
      this procedure. The flaps included a vertical rectus abdominis myocutaneous
      component and a 6th or 7th rib with adjacent muscle and skin to restore bone
      defects, internal lining, and external coverage. All donor sites were closed
      primarily. There were no flap losses and all patients gained improvements in
      facial contour, speech and swallow. Although technically complex, the PIMOC is
      reproducible and provides a safe and reliable option for salvage head and neck
      reconstruction. The harvest of the 6th or 7th rib and rectus abdominis muscle
      renders an acceptable donor site.

PMID- 29021618
TI  - Superconductivity in Empty Bands and Multiple Order Parameter Chirality.
AB  - Recent experiments have shown rotation of the plane of polarization of light
      reflected from the surface of some superconductors. The photon energy exceeds the
      electronic bandwidth, so that completely filled or completely empty bands must
      play a role. We show that in strong-coupling theory a Coulomb interaction can
      produce an order parameter in the unoccupied band that explains the observations.
      Thus the phenomenology puts tight constraints on the form of the order parameter
      in different bands. We propose that the experiments have detected, for the first
      time, the existence of a superconducting order parameter in a band far from the
      Fermi energy. This is only possible because of the sensitivity to delicate
      symmetries: a positive Kerr effect indicates that time reversal and certain
      mirror symmetries are broken in the ordered phase. Furthermore, detailed analysis
      of the results implies that in UPt3 there exist bands that have different order
      parameter chiralities, opening up complex new possibilities for topological
      superconductivity.

PMID- 29021619
TI  - Pan-cancer analysis of bi-allelic alterations in homologous recombination DNA
      repair genes.
AB  - BRCA1 and BRCA2 are involved in homologous recombination (HR) DNA repair and are
      germ-line cancer pre-disposition genes that result in a syndrome of hereditary
      breast and ovarian cancer (HBOC). Whether germ-line or somatic alterations in
      these genes or other members of the HR pathway and if mono- or bi-allelic
      alterations of HR-related genes have a phenotypic impact on other cancers remains
      to be fully elucidated. Here, we perform a pan-cancer analysis of The Cancer
      Genome Atlas (TCGA) data set and observe that bi-allelic pathogenic alterations
      in homologous recombination (HR) DNA repair-related genes are prevalent across
      many malignancies. These bi-allelic alterations often associate with genomic
      features of HR deficiency. Further, in ovarian, breast and prostate cancers, bi
      allelic alterations are mutually exclusive of each other. The combination of
      these two properties facilitates reclassification of variants of unknown
      significance affecting DNA repair genes, and may help personalize HR directed
      therapies in the clinic.Germline mutations in homologous recombination (HR) DNA
      repair genes are linked to breast and ovarian cancer. Here, the authors show that
      mutually exclusive bi-allelic inactivation of HR genes are present in other
      cancer types and associated with genomic features of HR deficiency, expanding the
      potential use of HR-directed therapies.

PMID- 29021620
TI  - Exotic superfluidity and pairing phenomena in atomic Fermi gases in mixed
      dimensions.
AB  - Atomic Fermi gases have been an ideal platform for simulating conventional and
      engineering exotic physical systems owing to their multiple tunable control
      parameters. Here we investigate the effects of mixed dimensionality on the
      superfluid and pairing phenomena of a two-component ultracold atomic Fermi gas
      with a short-range pairing interaction, while one component is confined on a one
      dimensional (1D) optical lattice whereas the other is in a homogeneous 3D
      continuum. We study the phase diagram and the pseudogap phenomena throughout the
      entire BCS-BEC crossover, using a pairing fluctuation theory. We find that the
      effective dimensionality of the non-interacting lattice component can evolve from
      quasi-3D to quasi-1D, leading to strong Fermi surface mismatch. Upon pairing, the
      system becomes effectively quasi-two dimensional in the BEC regime. The behavior
      of T c bears similarity to that of a regular 3D population imbalanced Fermi gas,
      but with a more drastic departure from the regular 3D balanced case, featuring
      both intermediate temperature superfluidity and possible pair density wave ground
      state. Unlike a simple 1D optical lattice case, T c in the mixed dimensions has a
      constant BEC asymptote.

PMID- 29021621
TI  - Protein interaction network of alternatively spliced NudCD1 isoforms.
AB  - NudCD1, also known as CML66 or OVA66, is a protein initially identified as
      overexpressed in patients with chronic myelogenous leukemia. The mRNA of NudCD1
      is expressed in heart and testis of normal tissues, and is overexpressed in
      several cancers. Previous studies have shown that the expression level of the
      protein correlates with tumoral phenotype, possibly interacting upstream of the
      Insulin Growth Factor - 1 Receptor (IGF-1R). The gene encoding the NudCD1 protein
      consists of 12 exons that can be alternative spliced, leading to the expression
      of three different isoforms. These isoforms possess a common region of 492 amino
      acids in their C-terminus region and have an isoform specific N-terminus. To
      determine the distinct function of each isoforms, we have localised the isoforms
      within the cells using immunofluorescence microscopy and used a quantitative
      proteomics approach (SILAC) to identify specific protein interaction partners for
      each isoforms. Localization studies showed a different subcellular distribution
      for the different isoforms, with the first isoform being nuclear, while the other
      two isoforms have distinct cytoplasmic and nuclear location. We found that the
      different NudCD1 isoforms have unique interacting partners, with the first
      isoform binding to a putative RNA helicase named DHX15 involved in mRNA splicing.

PMID- 29021622
TI  - The circadian transcriptome of marine fish (Sparus aurata) larvae reveals highly
      synchronized biological processes at the whole organism level.
AB  - The regulation of circadian gene expression remains largely unknown in farmed
      fish larvae. In this study, a high-density oligonucleotide microarray was used to
      examine the daily expression of 13,939 unique genes in whole gilthead sea bream
      (Sparus aurata) larvae with fast growth potentiality. Up to 2,229 genes were
      differentially expressed, and the first two components of Principal Component
      Analysis explained more than 81% of the total variance. Clustering analysis of
      differentially expressed genes identified 4 major clusters that were triggered
      sequentially, with a maximum expression at 0 h, 3 h, 9-15 h and 18-21 h zeitgeber
      time. Various core clock genes (per1, per2, per3, bmal1, cry1, cry2, clock) were
      identified in clusters 1-3, and their expression was significantly correlated
      with several genes in each cluster. Functional analysis revealed a daily
      consecutive activation of canonical pathways related to phototransduction,
      intermediary metabolism, development, chromatin remodeling, and cell cycle
      regulation. This daily transcriptome of whole larvae resembles a cell cycle
      (G1/S, G2/M, and M/G1 transitions) in synchronization with multicellular
      processes, such as neuromuscular development. This study supports that the
      actively feeding fish larval transcriptome is temporally organized in a 24-h
      cycle, likely for maximizing growth and development.

PMID- 29021623
TI  - Preference for novel faces in male infant monkeys predicts cerebrospinal fluid
      oxytocin concentrations later in life.
AB  - The ability to recognize individuals is a critical skill acquired early in life
      for group living species. In primates, individual recognition occurs
      predominantly through face discrimination. Despite the essential adaptive value
      of this ability, robust individual differences in conspecific face recognition
      exist, yet its associated biology remains unknown. Although pharmacological
      administration of oxytocin has implicated this neuropeptide in face perception
      and social memory, no prior research has tested the relationship between
      individual differences in face recognition and endogenous oxytocin
      concentrations. Here we show in a male rhesus monkey cohort (N = 60) that infant
      performance in a task used to determine face recognition ability (specifically,
      the ability of animals to show a preference for a novel face) robustly predicts
      cerebrospinal fluid, but not blood, oxytocin concentrations up to five years
      after behavioural assessment. These results argue that central oxytocin biology
      may be related to individual face perceptual abilities necessary for group
      living, and that these differences are stable traits.

PMID- 29021625
TI  - Quasi-two-dimensional superconductivity from dimerization of atomically ordered
      AuTe2Se4/3 cubes.
AB  - The emergent phenomena such as superconductivity and topological phase
      transitions can be observed in strict two-dimensional (2D) crystalline matters.
      Artificial interfaces and one atomic thickness layers are typical 2D materials of
      this kind. Although having 2D characters, most bulky layered compounds, however,
      do not possess these striking properties. Here, we report quasi-2D
      superconductivity in bulky AuTe2Se4/3, where the reduction in dimensionality is
      achieved through inducing the elongated covalent Te-Te bonds. The atomic
      resolution images reveal that the Au, Te, and Se are atomically ordered in a
      cube, among which are Te-Te bonds of 3.18 and 3.28 A. The superconductivity at
      2.85 K is discovered, which is unraveled to be the quasi-2D nature owing to the
      Berezinsky-Kosterlitz-Thouless topological transition. The nesting of nearly
      parallel Fermi sheets could give rise to strong electron-phonon coupling. It is
      proposed that further depleting the thickness could result in more topologically
      related phenomena.Emergent phenomena often appear in crystals in the two
      dimensional limit but are rare in bulky compounds. Here, Guo et al. report a
      quasi-two-dimensional superconductivity in a bulk material AuTe2Se4/3 at 2.85 K,
      potentially owing to a topological transition.

PMID- 29021626
TI  - Vector Form of Symmetry Degree.
AB  - ABSRACT: Symmetry degree is utilized to characterize the asymmetry of a physical
      system with respect to a symmetry group. The scalar form of symmetry degree (SSD)
      based on Frobenius-norm has been introduced recently to present a quantitative
      description of symmetry. Here we present the vector form of the symmetry degree
      (VSD) which possesses more advantages than the SSD. Mathematically, the dimension
      of VSD is defined as the conjugacy class number of the symmetry group, the square
      length of the VSD gives rise to the SSD and the direction of VSD is determined by
      the orders of the conjugacy classes. The merits of applying VSD both for finite
      and infinite symmetry groups include the additional information of broken
      symmetry operators with single symmetry breaking perturbation, and the capability
      of distinguishing distinct symmetry breaking perturbations which exactly give
      rise to degenerate SSD. Additionally, the VSD for physical systems under symmetry
      breaking perturbations can be regarded as a projection of the initial VSD without
      any symmetry breaking perturbations, which can be described by an evolution
      equation. There are the same advantages by applying VSD for the accidental
      degeneracy and spontaneous symmetry breaking.

PMID- 29021624
TI  - MKK6 controls T3-mediated browning of white adipose tissue.
AB  - Increasing the thermogenic capacity of adipose tissue to enhance organismal
      energy expenditure is considered a promising therapeutic strategy to combat
      obesity. Here, we report that expression of the p38 MAPK activator MKK6 is
      elevated in white adipose tissue of obese individuals. Using knockout animals and
      shRNA, we show that Mkk6 deletion increases energy expenditure and thermogenic
      capacity of white adipose tissue, protecting mice against diet-induced obesity
      and the development of diabetes. Deletion of Mkk6 increases T3-stimulated UC P1
      expression in adipocytes, thereby increasing their thermogenic capacity.
      Mechanistically, we demonstrate that, in white adipose tissue, p38 is activated
      by an alternative pathway involving AMPK, TAK, and TAB. Our results identify MKK6
      in adipocytes as a potential therapeutic target to reduce obesity.Brown and beige
      adipose tissues dissipate heat via uncoupling protein 1 (UCP1). Here the authors
      show that the stress activated kinase MKK6 acts as a repressor of UCP1
      expression, suggesting that its inhibition promotes adipose tissue browning and
      increases organismal energy expenditure.

PMID- 29021627
TI  - Dispersal of thermophilic beetles across the intercontinental Arctic forest belt
      during the early Eocene.
AB  - Massive biotic change occurred during the Eocene as the climate shifted from warm
      and equable to seasonal and latitudinally stratified. Mild winter temperatures
      across Arctic intercontinental land bridges permitted dispersal of frost
      intolerant groups until the Eocene-Oligocene boundary, while trans-Arctic
      dispersal in thermophilic groups may have been limited to the early Eocene,
      especially during short-lived hyperthermals. Some of these lineages are now
      disjunct between continents of the northern hemisphere. Although Eocene climate
      change may have been one of the most important drivers of these ancient patterns
      in modern animal and plant distributions, its particular events are rarely
      implicated or correlated with group-specific climatic requirements. Here we
      explored the climatic and geological drivers of a particularly striking
      Neotropical-Oriental disjunct distribution in the rove beetle Bolitogyrus, a
      suspected Eocene relict. We integrated evidence from Eocene fossils,
      distributional and climate data, paleoclimate, paleogeography, and phylogenetic
      divergence dating to show that intercontinental dispersal of Bolitogyrus ceased
      in the early Eocene, consistent with the termination of conditions required by
      thermophilic lineages. These results provide new insight into the poorly known
      and short-lived Arctic forest community of the Early Eocene and its surviving
      lineages.

PMID- 29021628
TI  - Unified treatment of spin torques using a coupled magnetisation dynamics and
      three-dimensional spin current solver.
AB  - A three-dimensional spin current solver based on a generalised spin drift
      diffusion description, including the bulk and interfacial spin Hall effects, is
      integrated with a magnetisation dynamics solver. The resulting model is shown to
      simultaneously reproduce the spin-orbit torques generated using the spin Hall
      effect, spin pumping torques generated by magnetisation dynamics in multilayers,
      as well as the spin transfer torques acting on magnetisation regions with spatial
      gradients, whilst field-like and spin-like torques are reproduced in a spin valve
      geometry. Two approaches to modelling interfaces are analysed, one based on the
      spin mixing conductance and the other based on continuity of spin currents where
      the spin dephasing length governs the absorption of transverse spin components.
      In both cases analytical formulas are derived for the spin-orbit torques in a
      heavy metal/ferromagnet bilayer geometry, showing in general both field-like and
      damping-like torques are generated. The limitations of the analytical approach
      are discussed, showing that even in a simple bilayer geometry, due to the non
      uniformity of the spin currents, a full three-dimensional treatment is required.
      The model is further applied to the analysis of the spin Hall angle in Pt by
      reproducing published experimental ferromagnetic resonance data in the bilayer
      geometry.

PMID- 29021629
TI  - Electrical magnetochiral effect induced by chiral spin fluctuations.
AB  - Chirality of matter can produce unique responses in optics, electricity and
      magnetism. In particular, magnetic crystals transmit their handedness to the
      magnetism via antisymmetric exchange interaction of relativistic origin,
      producing helical spin orders as well as their fluctuations. Here we report for a
      chiral magnet MnSi that chiral spin fluctuations manifest themselves in the
      electrical magnetochiral effect, i.e. the nonreciprocal and nonlinear response
      characterized by the electrical resistance depending on inner product of current
      and magnetic field. Prominent electrical magnetochiral signals emerge at specific
      temperature-magnetic field-pressure regions: in the paramagnetic phase just above
      the helical ordering temperature and in the partially-ordered topological spin
      state at low temperatures and high pressures, where thermal and quantum spin
      fluctuations are conspicuous in proximity of classical and quantum phase
      transitions, respectively. The finding of the asymmetric electron scattering by
      chiral spin fluctuations may explore new electromagnetic functionality in chiral
      magnets.The magnetism-induced chirality in electron transportation is of
      fundamental importantance in condensed matter physics but the origin is still
      unclear. Here the authors demonstrate that the asymmetric electron scattering by
      chiral spin fluctuations can be the key to the electrical magnetochiral effect in
      MnSi.

PMID- 29021630
TI  - Controlled Deposition of Particles in Porous Media for Effective Aquifer
      Nanoremediation.
AB  - In this study, a model assisted strategy is developed to control the distribution
      of colloids in porous media in the framework of nanoremediation, an innovative
      environmental nanotechnology aimed at reclaiming contaminated aquifers. This
      approach is exemplified by the delivery of humic acid-stabilized iron oxide
      nanoparticles (FeOx), a typical reagent for in situ immobilization of heavy
      metals. By tuned sequential injections of FeOx suspensions and of solutions
      containing a destabilizing agent (i.e. calcium or magnesium), the two fronts,
      which advance at different rates, overlap at the target location (i.e., the
      central portion) of the porous systems. Here, the particles deposit and
      accumulate irreversibly, creating a reactive zone. An analytical expression
      predicting the position of the clustering zone in 1D systems is derived from
      first principles of advective-dispersive transport. Through this equation, the
      sequence and duration of the injection of the different solutions in the medium
      is assessed. The model robustness is demonstrated by its successful application
      to various systems, comprising the use of different sands or immobilizing
      cations, both in 1D and 2D geometries. The method represents an advancement in
      the control of nanomaterial fate in the environment, and could enhance
      nanoremediation making it an effective alternative to more conventional
      techniques.

PMID- 29021632
TI  - Arctic cryosphere and Milankovitch forcing of Great Basin paleoclimate.
AB  - Although Great Basin paleoclimate history has been examined for more than a
      century, the orbital-scale paleoclimate forcings remain poorly understood. Here
      we show - by a detailed phasing analysis of a well-dated stalagmite delta18O time
      series - that Great Basin paleoclimate is linearly related to, but lagged, the
      23,000 yr precession cycle in northern hemisphere summer insolation by an average
      of 3240 years (-900 to 6600 yr range) over the last two glacial cycles. We
      interpret these lags as indicating that Great Basin climate is sensitive to and
      indirectly forced by changes in the cryosphere, as evidenced by fast and strong
      linkages to global ice volume and Arctic paleoclimate indicators. Mid-latitude
      atmospheric circulation was likely impacted by a northward shifted storm track
      and higher pressure over the region arising from decreased sea ice and snow
      cover. Because anthropogenic warming is expected to reduce northern hemisphere
      snow and ice cover, continued increase in atmospheric greenhouse gases is likely
      to result in warming and drying over coming centuries that will amplify a warming
      trend that began ~2400 years ago.

PMID- 29021631
TI  - Deficiency of peroxiredoxin 6 or inhibition of its phospholipase A2 activity
      impair the in vitro sperm fertilizing competence in mice.
AB  - Prdx6 -/- male mice are subfertile, and the deficiency or inactivation of
      Peroxiredoxins (PRDXs) is associated with human male infertility. We elucidate
      the impact of the lack of PRDX6 or inhibition of its calcium-independent
      phospholipase A2 (Ca2+-iPLA2) activity by MJ33 on fertilization competence of
      mouse spermatozoa. Sperm motility, viability, fertilization and blastocyst rates
      were lower in Prdx6 -/- spermatozoa than in C57BL/6J wild-type (WT) controls (p
      <= 0.05). MJ33 inhibited the PRDX6 Ca2+-iPLA2 activity and reduced these
      parameters in WT spermatozoa compared with controls (p <= 0.05). Levels of lipid
      peroxidation and of superoxide anion (O2*?) were higher in Prdx6 -/- than in WT
      spermatozoa (p <= 0.05). MJ33 increased the levels of lipid peroxidation and
      mitochondrial O2*? production in treated versus non-treated WT spermatozoa.
      Acrosome reaction, binding to zona pellucida and fusion with the oolemma were
      lower in Prdx6 -/- capacitated spermatozoa than WT capacitated controls and lower
      in WT spermatozoa treated with the PRDX6 inhibitor. In conclusion, the inhibition
      of the PRDX6 Ca2+-iPLA2 activity promotes an oxidative stress affecting
      viability, motility, and the ability of mouse spermatozoa to fertilize oocytes.
      Thus, PRDX6 has a critical role in the protection of the mouse spermatozoon
      against oxidative stress to assure fertilizing competence.

PMID- 29021635
TI  - Four Cases of Valvular Diseases Due to Nonpenetrating Cardiac Trauma.
AB  - During the past 15 years we have managed four patients who suffered isolated
      valvular lesions from blunt chest trauma. Three patients were injured intraffic
      accidents and another fell from a height. Injured valves were mitral valves in
      three patients, tricuspid valves in two and aortic valve in one. One individual
      had a combination of aortic, mitral, and tricuspid valvular lesions.The
      procedures performed were mitral valve replacement in 2 patients and mitral
      repair in one, tricuspid valve replacement in one and repair in one, aortic valve
      replacement in one. The outcome of those patients were fairly well and all
      returned to their regular jobs.

PMID- 29021634
TI  - Lipopolysaccharide accelerates fine particulate matter-induced cell apoptosis in
      human lung bronchial epithelial cells.
AB  - OBJECTIVES: The aim of the study has been to investigate the effect of the
      Standard Reference Material of fine particulate matter (SRM 2786) on cytotoxicity
      and apoptosis in human lung bronchial epithelial cells (16HBE cells). Whether the
      lipopolysaccharide (LPS)-induced inflammation could further accelerate cell
      apoptosis induced by SRM 2786 stimulation has also been determined. MATERIAL AND
      METHODS: 16HBE cells were exposed to various doses of SRM 2786 with or without
      LPS. The following parameters: cytotoxicity, apoptotic rate, Bax/Bcl-2
      expression, nitric oxide (NO) production, and reactive oxygen species (ROS)
      generation were measured. RESULTS: The results have shown that SRM 2786 induces
      cell damage and apoptosis of 16HBE cells as demonstrated by significant decrease
      in expression of Bcl-2 and increase in expression of Bax. When compared with the
      control cells, the apoptotic rate of cells treated by 500 MUg/ml of SRM 2786
      increased from 2.43+/-0.21% to 43.96+/-2.95% (p < 0.01). Further, there was an
      elevated production of NO and ROS post SRM 2786 treatment. The level of NO in
      cells treated with 500 MUg/ml of SRM 2786 was 18.33+/-1.02 MUmol/l whereas that
      of control cells was 1.58+/-0.31 MUmol/l (p < 0.01). When compared with the
      control group, the level of intracellular ROS increased by 24% after treatment
      with 500 MUg/ml of SRM 2786 (p < 0.05). In addition, LPS pre-treatment may
      accelerate cell apoptosis by increasing generation of NO and ROS followed by SRM
      2786 stimulation. When compared to cells treated with 125 MUg/ml of SRM 2786
      alone, the levels of NO and ROS in cells pretreated with LPS increased by 28% and
      11.6%, respectively (p < 0.05), and the apoptotic rate increased from 34.62+/
      4.44% to 54.11+/-3.34% (p < 0.01). CONCLUSIONS: These findings have suggested
      that in vitro exposure to SRM 2786 could induce 16HBE cells apoptosis probably by
      means of the mechanism involving the generation of free radicals, while the
      degree of apoptosis would be further aggravated under inflammation condition. Int
      J Occup Med Environ Health 2018;31(2):173-183.

PMID- 29021633
TI  - Structure and function of the alternatively spliced isoforms of the ecdysone
      receptor gene in the Chinese mitten crab, Eriocheir sinensis.
AB  - Alternative splicing is an essential molecular mechanism that increase the
      protein diversity of a species to regulate important biological processes.
      Ecdysone receptor (EcR), an essential nuclear receptor, is essential in the
      molting, growth, development, reproduction, and regeneration of crustaceans. In
      this study, the whole sequence of EcR gene from Eriocheir sinensis was obtained.
      The sequence was 45,481 bp in length with 9 exons. Moreover, four alternatively
      spliced EcR isoforms (Es-EcR-1, Es-EcR-2, Es-EcR-3 and Es-EcR-4) were identified.
      The four isoforms harbored a common A/B domain and a DNA-binding region but
      different D domains and ligand-binding regions. Three alternative splicing
      patterns (alternative 5' splice site, exon skipping, and intron retention) were
      identified in the four isoforms. Functional studies indicated that the four
      isoforms have specific functions. Es-EcR-3 may play essential roles in regulating
      periodic molting. Es-EcR-2 may participate in the regulation of ovarian
      development. Our results indicated that Es-EcR has broad regulatory functions in
      molting and development and established the molecular basis for the investigation
      of ecdysteroid signaling related pathways in E. sinensis.

PMID- 29021636
TI  - Evaluation of Pulmonary Artery Angioplasty for Lung Cancer Surgery: A Com-parison
      with Pneumonectomy.
AB  - We performed pulmonary artery angioplasty in 19 patients with lung cancer. The
      procedure consists of segmental or wedge resrection of the infiltrated pulmonary
      artery stem followed by reconstruction to avoid pneumonectomy and preserve
      pulmonary function. Among these cases "double sleeve resection" was performed in
      10 cases. The 5-year survival of the angioplasty patients was poor at a rate of
      11&#65285;, but not significantly different from the survival rates for those
      patients who underwent bronchoplasy alone or pneumonectomy. A promising prognosis
      may be expected in cases with N0 and N1 lymph node metastasis. However, this
      procedure may not replace pneumonectmy in patients with intact pulmonary
      function.

PMID- 29021637
TI  - Physical frailty and fitness of older driver.
AB  - AIM: to analyze the association between physical frailty and the results of
      fitness capacity exams for driving vehicles among elder Brazilians. METHODS: this
      is a cross sectional study, performed in traffic medicine clinics of the city of
      Curitiba (Brazil). The data was collected through the physical frailty tests, the
      use of a structured questionnaire, and searches on the records of the Brazilian
      National Register of Qualified Drivers.To analyze the information, the authors
      used descriptive statistics and non-parametrical tests. RESULTS: One hundred
      seventy two elderly people, of whom 56.4% pre-fragile and 43.6% non-fragile.
      25.0% were considered fit for driving, 68.6% were considered fit, but with some
      restrictions, and 6.4% were placed as temporarily unfit for driving. There was no
      association between frailty condition and the final results for driving fitness
      (p= 0.8934). Physical frailty was significantly associated to the restrictions
      observed for those who were fit under restrictions (p= 0.0313), according to the
      weekly amount of kilometers traveled (p= 0.0222), and to car accidents occurred
      after the age of 60 (p= 0.0165). CONCLUSION: Physical frailty was significantly
      associated to the restrictions related to driving, reason to which makes
      important to manage frailty over this group of drivers. However, no association
      observed between physical frailty and the final result for driving vehicles.

PMID- 29021638
TI  - Real-time PCR assay for the diagnosis of pleural tuberculosis.
AB  - INTRODUCTION: The diagnosis of pleural tuberculosis requires an invasive and time
      consuming reference method. Polymerase chain reaction (PCR) is rapid, but
      validation in pleural tuberculosis is still weak. OBJECTIVE: To establish the
      operating characteristics of real-time polymerase chain reaction (RT-PCR)
      hybridization probes for the diagnosis of pleural tuberculosis. METHODS: The
      validity of the RT-PCR hybridization probes was evaluated compared to a composite
      reference method by a cross-sectional study at the Hospital Universitario de la
      Samaritana. 40 adults with lymphocytic pleural effusion were included. Pleural
      tuberculosis was confirmed (in 9 patients) if the patient had at least one of
      three tests using the positive reference method: Ziehl-Neelsen or Mycobacterium
      tuberculosis culture in fluid or pleural tissue, or pleural biopsy with
      granulomas. Pleural tuberculosis was ruled out (in 31 patients) if all three
      tests were negative. The operating characteristics of the RT-PCR, using the Mid-P
      Exact Test, were determined using the OpenEpi 2.3 Software (2009). RESULTS: The
      RT-PCR hybridization probes showed a sensitivity of 66.7% (95% CI: 33.2%-90.7%)
      and a specificity of 93.5% (95% CI: 80.3%-98.9%). The PPV was 75.0% (95% CI:
      38.8%-95.6%) and a NPV of 90.6% (95% CI: 76.6%-97.6%). Two false positives were
      found for the test, one with pleural mesothelioma and the other with chronic
      pleuritis with mesothelial hyperplasia. CONCLUSIONS: The RT-PCR hybridization
      probes had good specificity and acceptable sensitivity, but a negative value
      cannot rule out pleural tuberculosis.

PMID- 29021639
TI  - Mutational spectrum in breast cancer associated BRCA1 and BRCA2 genes in
      Colombia.
AB  - INTRODUCTION: The risk of developing breast and ovarian cancer is higher in
      families that carry mutations in BRCA1 or BRCA2 genes, and timely mutation
      detection is critical. OBJECTIVE: To identify the presence of mutations in the
      Colombian population and evaluate two testing strategies. METHODS: From a total
      universe of 853 individual blood samples referred for BRCA1 and BRCA2 typing, 256
      cases were analyzed by complete direct sequencing of both genes in Myriad
      Genetics, and the remaining 597 cases were studied by partial sequencing based on
      founder mutations in a PCR test designed by ourselves ("Profile Colombia").
      RESULTS: We found 107 patients carrying deleterious mutations in this group of
      patients, 69 (64.5%) located in BRCA1, and 38 (35.5%) in BRCA2. Overall, we
      detected 39 previously unreported mutations in Colombia (22 in BRCA1 and 17 in
      BRCA2) and only 4 out of the 6 previously reported founder mutations. Sixty four
      out of 597 patients (10.7%) studied by "Profile Colombia" showed mutations in
      BRCA1 or BRCA2, and 41/256 patients (16%) showed mutations by complete BRCA1
      BRCA2 sequencing. CONCLUSIONS: The spectrum of 44 different mutations in Colombia
      as detected in our study is broader than the one previously reported for this
      country. "Profile Colombia" is a useful screening test to establish both founder
      and new mutations (detection rate of 10.7%) in cases with family history of
      breast cancer. Complete sequencing shows a detection rate of 16.0%, and should
      complement the study of the genetic basis of this disease.

PMID- 29021640
TI  - Population attributable fractions for colorectal cancer and red and processed
      meats in Colombia - a macro-simulation study.
AB  - AIM: to estimate the population attributable risk of consumption of red and
      processed meat for colorectal cancer in Colombia. METHODS: to model the expected
      incidence of colorectal cancer in the hypothetical situation of no red and
      processed meat consumption in Colombia, for the year 2010. A dynamic
      macrosimulation model, PREVENT 3.01, was used to integrate available cancer
      incidence, meat consumption prevalence and associated risk data and to evaluate
      the impact of eliminating red and processed meat from the Colombian diet on
      national colorectal cancer incidence. RESULTS: Eliminating consumption of red
      meat altogether from the Colombian diet resulted in reductions in age
      standardized colorectal cancer incidence, translating in reductions of 331 males
      (PAF 13%) and 297 female cases (PAF 10%). Eliminating processed meats had
      slightly stronger effects, with decreases of 362 males (PAF 14%) and 388 female
      cases (PAF 13%). CONCLUSIONS: A substantial proportion of the burden of
      colorectal cancer in Colombia can be attributed to the consumption of red and
      processed meat.

PMID- 29021641
TI  - Zidovudine/Lamivudine vs. Abacavir/Lamivudine vs. Tenofovir/Emtricitabine in
      fixed-dose combinations as initial treatment for HIV patients: a systematic
      review and network meta-analysis.
AB  - INTRODUCTION: Initial treatment of the HIV is based on the use of three drugs,
      two of which are nucleoside analog reverse-transcriptase inhibitors. There are
      three combinations of these drugs which have been approved by different
      guidelines, each with divergent results in terms of efficacy and safety.
      OBJECTIVE: To compare the efficacy and safety of these three combinations.
      METHODS: Systematic review and network meta-analysis of randomized clinical
      trials comparing fixed doses of Tenofovir Disoproxil Fumarate / Emtricitabine
      (TDF/FTC), Abacavir / Lamivudine (ABC/3TC) and Zidovudine / Lamivudine (ZDV/3TC).
      RESULTS: Seven clinical trials met the eligibility criteria. The results
      suggested higher efficacy with TDF/FTC vs. ABC/3TC at 96 weeks and vs. ZDV/3TC at
      48 weeks. However, there is clinical and statistical heterogeneity. Subgroup
      analysis were performed by third drug and by level of viral load prior to
      treatment, and found no differences in virological control. Network meta-analysis
      could only be carried out with TDF/FTC vs. ZDV/3TC, and the proportion of
      patients with virological response, with no differences at 48 weeks nor at 96
      weeks. Direct comparisons showed an increased risk of bone marrow suppression of
      ZDV/3TC vs. TDF/FTC and of ABC/3TC hypersensitivity reactions vs. ZDV/3TC.
      CONCLUSIONS: The results did not show differences in effectiveness among the
      interventions. However, due to the heterogeneity of the third drug and the follow
      up time between the included studies, this result is not definitive. The results
      raise the need for further studies to help improve treatment recommendations in
      patients infected with HIV.

PMID- 29021642
TI  - Bevacizumab as a treatment for hereditary hemorrhagic telangiectasia in children:
      a case report.
AB  - CASE DESCRIPTION: Five-year-old female patient with hereditary hemorrhagic
      telangiectasia. CLINICAL FINDINGS: Deterioration of cardiopulmonary function with
      higher oxygen requirements secondary to pulmonary arteriovenous shunts,
      epistaxis. TREATMENT AND OUTCOME: The patient was treated with the monoclonal
      antibody bevacizumab, which inhibits the vascular endothelial growth factor, with
      good clinical outcome. CLINICAL RELEVANCE: Hereditary hemorrhagic telangiectasia
      is an autosomal dominant disorder characterized by arteriovenous malformations in
      different organs, making its clinical presentations varied. Systemic therapeutic
      options for a generalized disease are limited. The monoclonal antibody
      bevacizumab, seems to be a good option in this disorder. Although reported as
      successful in adult population, its use in pediatric population has not yet been
      reported. Here we report the use of bevacizumab in a 5-year-old female patient
      with hereditary hemorrhagic telangiectasia, showing clinical benefits and good
      outcome.

PMID- 29021643
TI  - Cryptococcal cerebellitis in no-VIH patient.
AB  - INTRODUCTION: Cryptococcosis is an opportunistic fungal infection whose etiology
      is Cryptococcus neofromans / C. gattii, complex which affects immunocompromised
      patients mainly. Meningeal infection is one of the most common presentations, but
      cerebellar affection is rare. CASE DESCRIPTION: Male patient with 65 old years,
      from an area of subtropical climate with chronic exposure to poultry, without
      pathological antecedents, who presented clinical picture consistent with
      headache, fever, seizures and altered mental status. CLINICAL FINDINGS AND
      DIAGNOSTIC METHODS: Initially without menigeal signs or intracranial hypertension
      and normal neurological examination. Later, the patient developed ataxia,
      dysdiadochokinesia and limb loss. By lumbar punction and image of nuclear
      magnetic resonance (NMR) cerebellitis cryptococcal was diagnosticated. TREATMENT:
      Antifungal therapy with amphotericin B and fluconazole was performed, however the
      patient died. CLINICAL RELEVANCE: The cryptococcosis has different presentations,
      it's a disease whose incidence has been increasing since the advent of the HIV /
      AIDS pandemy, however the commitment of the encephalic parenchyma and in
      particular the cerebellum is considered rare. In this way we are facing the first
      case of cryptococcal cerebellitis in our midst.

PMID- 29021644
TI  - Reflections on Afro-descendant origin and the outcome of dengue fever cases in
      Colombia.

PMID- 29021645
TI  - Research training during residency.

PMID- 29021646
TI  - What's inside.

PMID- 29021647
TI  - Roundup.

PMID- 29021648
TI  - Market forces in urological practice.

PMID- 29021649
TI  - Follow-up urodynamics in patients with neurogenic bladder.
AB  - INTRODUCTION: Neurogenic bladder patients are at long-term risk of secondary
      upper urinary tract damage. Symptoms are unreliable and follow-up urodynamics is
      the only method of ascertaining safety of bladder pressures. This review examines
      the recommendations, shortcomings and utilization of existing guidelines. The
      evidence with regard to follow-up urodynamics in different settings relevant to
      neurogenic bladder is evaluated and an algorithm is proposed. METHODS: A pubmed
      search was conducted for studies on follow-up urodynamics in patients with
      neurogenic bladder. Additional search was made of secondary sources including
      reviews and guidelines. RESULTS: The need for follow-up urodynamics should be
      considered in all patients undergoing an initial assessment and weighed against
      the risks. Existing guidelines, while unanimous in their recommendation of its
      utilization, give scant details regarding its incorporation in clinical
      management. Follow-up urodynamics can document efficacy and identify the need for
      escalation of therapy in patients on intermittent catheterization and
      antimuscarinics. Patients with spinal injury, spinal dysraphism and anorectal
      malformations are at higher risk for upper tract damage. Follow-up urodynamics
      can help identify patients suitable for intravesical botulinum and mark those
      destined for failure. Patients undergoing augmentation cystoplasty may be
      candidates for less aggressive urodynamic follow-up. CONCLUSIONS: Neurogenic
      bladder is managed by a broad cross-section of physicians. Clear recommendations
      and a management algorithm are important for improving patient care. Follow-up
      urodynamics can identify patients at risk, prevent renal dysfunction and improve
      the quality of life. There is an urgent need for more evidence on this important
      subject.

PMID- 29021651
TI  - MicroRNA-21 could be a molecular marker to predict the recurrence of nonmuscle
      invasive bladder cancer.
AB  - INTRODUCTION: High relapse rate of nonmuscle invasive bladder cancer (NMIBC) is a
      major challenge. Overexpression of microRNA-21 (miR-21) which targets phosphatase
      and tensin homolog (PTEN), a gene associated with malignancy, has been reported
      in the bladder tumor tissue compared to normal mucosa by us and others. We have
      tested whether miR-21 levels in bladder mucosa could predict tumor recurrence.
      METHODS: In a prospective cohort setting, tumor tissues and normal bladder mucosa
      (NBM) were taken from BC patients during transurethral resection of bladder
      tumor. Age- and ethnicity-matched NBM from benign prostate hyperplasia patients
      was taken as controls. The expression of miR-21 was analyzed using quantitative
      reverse transcription polymerase chain reaction. Patients were followed for 4
      years for tumor reoccurrence. Postoperative recurrence were recorded and
      calculated by Kaplan-Meier curve. RESULTS: In 31 patients, miR-21 was up
      regulated (>4-fold, P = 0.003), and PTEN levels were significantly lower (<7
      folds, P = 0.001) in tumor tissue relative to NBM. Moreover, the fold change in
      miR-21 levels was significantly higher (>3-folds, P = 0.03) in patients showing
      recurrence compared to those in which tumor did not recur. Further, Kaplan-Meier
      analysis shows overexpression of miR-21 corresponds to less time to recurrence
      with higher cumulative hazard. CONCLUSION: We found overexpression of miR-21 in
      tumor tissue and its association with recurrence, time to recurrence and
      invasiveness in BC. Quantification of miR-21 along with other pathological
      parameters could be more objective molecular approach to predict recurrence in
      NMIBC.

PMID- 29021650
TI  - Ureteral endometriosis: A systematic literature review.
AB  - INTRODUCTION: Ureteral endometriosis is a rare disease affecting women of
      childbearing age which presents with nonspecific symptoms and it may result in
      severe morbidity. The aim of this study was to review evidence about incidence,
      pathogenesis, clinical presentation, diagnosis, and management of ureteral
      endometriosis. MATERIALS AND METHODS: PubMed Central database was searched to
      identify studies reporting cases of ureteral endometriosis. "Ureter" or
      "Ureteral" and "Endometriosis" were used as key words. Database was searched for
      articles published since 1996, in English without restrictions regarding the
      study design. RESULTS: From 420 studies obtained through database search, 104
      articles were finally included in this review, including a total of 1384 patients
      with ureteral endometriosis. Data regarding age, location, pathological findings,
      and interventions were extracted. Mean patients' age was 38.6 years, whereas the
      therapeutic arsenal included hormonal, endoscopic, and/or surgical treatment.
      CONCLUSIONS: Ureteral endometriosis represents a diagnostic and therapeutic
      challenge for the clinicians and high clinical suspicion is needed to identify
      it.

PMID- 29021653
TI  - Are there any factors affecting the outcome of endoscopic sclerotherapy in
      filarial chyluria? A prospective study.
AB  - INTRODUCTION: Filarial chyluria is a frequent problem in India. While endoscopic
      therapy is the mainstay of treatment, it is not always successful. We aimed to
      determine parameters that affect outcomes of endoscopic sclerotherapy for
      filarial chyluria (FC). METHODS: Prospectively maintained data of FC patients who
      received endoscopic sclerotherapy between June 2011 and March 2015 were analyzed.
      Sclerotherapy included either povidone-iodine (0.1%) or silver nitrate (1%). The
      parameters recorded included clinical evaluation, urinary triglyceride
      (TG)/cholesterol, sclerotherapy treatment, and follow-up. RESULTS: One hundred
      and fifty-seven patients (male: female, 104:53) with a mean age (+/- standard
      deviation [SD]) 41.12 +/- 13.68 years underwent endoscopic sclerotherapy. Grade
      II (68.88%) chyluria was a most common presentation followed by Grade III
      (25.69%). One hundred and forty-four patients responded whereas six patients
      failed to respond; another seven were lost to follow up, and twenty patients had
      recurrence. Overall success rate was 86.11%. Baseline urinary TG (mean +/- SD)
      between success and recurrence group was 195.51 +/- 164.73 mg/dl and 652.65 +/-
      62.55 mg/dl and cholesterol (mean +/- SD) was 16.99 +/- 10.08 mg/dl and 89.07 +/-
      39.87 mg/dl, respectively. Patient with urinary TGs >300 mg/dl and urinary
      cholesterol >30 mg/dl had 3.2 and 1.3 times higher chance to have recurrence
      after endoscopic sclerotherapy, respectively. Choice of sclerosing agent (silver
      nitrate 1% versus povidone-iodine 0.1%) had no difference in success rate, but
      silver nitrate had slightly higher complications rate (25% vs. 20%). A higher
      number of instillations (>3) was associated with better success rate. Majority of
      the complications were either Clavien Grade 1 or 2. CONCLUSIONS: The factors
      predicting recurrence were higher clinical grade, higher number of pretreatment
      courses, and high urinary TG and cholesterol.

PMID- 29021652
TI  - Urine and serum fetuin-A levels in patients with urolithiasis.
AB  - INTRODUCTION: Fetuin-A is a glycoprotein secreted by liver and has been shown to
      inhibit extraosseous mineralization. Urolithiasis may be a manifestation in the
      urinary tract due to fetuin deficiency in urine. The objective of this study was
      to compare the 24-h urine and serum fetuin-A levels of patients with and without
      urolithiasis. METHODS: Serum and 24-h urine fetuin-A levels were measured in 41
      patients with bilateral, multiple, or recurrent urinary tract calculi (Group A)
      and 41 matched controls with no calculi (Group B). Fetuin levels were measured by
      enzyme linked immunosorbent assay. Serum and urine fetuin-A levels in the two
      groups were compared. RESULTS: The median (range) 24-h urine fetuin-A value in
      Group A was 11.9 (1.12-221) mg/day and in Group B was 37.7 (1.28-125) mg/day.
      This difference was statistically significant (Mann-Whitney test, P = 0.0169).
      The median (range) serum fetuin-A in Group A was 0.67 (0.05-2.68) g/L and in
      Group B was 0.99 (0.01-5.5) g/L. The difference between serum values in the two
      arms was not statistically significant (Mann-Whitney test, P = 0.1817). However,
      the serum creatinine-adjusted mean log serum fetuin and urine fetuin were
      significantly different in the two arms (P = 0.003). The mean +/- standard
      deviation (range) serum creatinine in Group A was 0.98 +/- 0.25 (0.56-1.58) mg%
      and in Group B was 0.83 +/- 0.16 (0.58-1.18) mg% (two sample t-test, P = 0.0031).
      CONCLUSIONS: Patients with urolithiasis have lower urine fetuin-A and creatinine
      adjusted serum fetuin-A levels.

PMID- 29021654
TI  - Use of a stopwatch to measure ejaculatory latency may not be accurate among
      Indian patients.
AB  - INTRODUCTION: Although the use of a stopwatch is recommended to record
      intravaginal ejaculatory latency time (IELT) for premature ejaculation, there is
      no Indian literature which assesses the reliability of this method among our
      patients. Hence, we assessed the accuracy of stopwatch-measured IELT and compared
      it with other methods such as number of thrusts and self-assessed IELT in an
      Indian context. METHODS: Between January 2015 and December 2015, couples with
      premature ejaculation (PE) confirmed with the Premature Ejaculation Diagnostic
      Tool were enrolled in this study. They were asked to report self-assessed IELT
      for the first 2 weeks, number of thrusts before ejaculation following vaginal
      penetration for the next 2 weeks, and stopwatch-clocked IELT for the last 2
      weeks. At each 2-week interval, the couples answered erectile/ejaculatory
      performance anxiety index questionnaire (EPAI). The data were analyzed at the end
      of 6 weeks. RESULTS: A total of 42 couples with an average married life of 5.53
      years were included in the study. Average stopwatch-clocked IELT was almost 1 min
      more than the self-reported IELT, which was statistically significant. The
      average number of thrusts reported was 6.31. Anxiety on the EPAI scale was
      maximum while using stopwatch to measure IELT. CONCLUSION: Use of stopwatch to
      clock the IELT does not appear to represent true IELT in Indian patients. Self
      assessed IELT correlated more accurately with symptoms of PE.

PMID- 29021655
TI  - Robot-assisted retroperitoneal lymph node dissection: Feasibility and outcome in
      postchemotherapy residual mass in testicular cancer.
AB  - INTRODUCTION: We aimed to evaluate the surgical feasibility, complication, and
      oncological outcome of robot-assisted retroperitoneal lymph node dissection (RA
      RPLND) in patients of testicular tumor with postchemotherapy residual
      retroperitoneal mass. METHODS: A total of 13 patients underwent RA-RPLND between
      January 2012 and September 2016 at our institute. A study was started on December
      2015, so data were collected retrospectively and prospectively regarding patient
      demography, tumor characteristics, surgical, pathological outcome, and
      oncological outcome. RESULTS: RA-RPLND was successfully completed in all the 13
      patients. Lateral approach was used in initial 12 patients with unilateral
      dissection in 11 patients and bilateral dissection after in 1 patient after
      repositioning in bilateral position. Supine robotic approach used in 1 patient.
      Median operative time was 200 min, median estimated blood loss was 120 ml, and
      median length of hospital stay was 4 days. The median yield of lymph node was 20.
      Three patients had positive lymph nodes, all had teratoma germ cell tumor. Ten
      patients had only necrosis in lymph nodes. After median follow-up 23 months
      (range 3-58 months), no systemic or retroperitoneal recurrence was found. Four
      patients developed chyle leak. One patient was managed conservatively with diet
      modification, one with intranodal lipiodol lymphangiography and two patients were
      managed surgically. CONCLUSION: RA-RPLND is safe and feasible for
      postchemotherapy residual mass with accepted compilation rate, but larger studies
      are required to establish its diagnostic and therapeutic utility along with
      safety of the procedure.

PMID- 29021656
TI  - A randomized controlled study comparing the standard, tubeless, and totally
      tubeless percutaneous nephrolithotomy procedures for renal stones from a tertiary
      care hospital.
AB  - INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is an effective treatment for
      renal stones. Due to the significant pain and morbidity after standard PCNL
      because of nephrostomy tubes, various modifications of PCNL are being performed.
      We report a randomized trial comparing these modalities. MATERIALS AND METHODS: A
      total of 75 patients were randomized into three groups of 25 each: standard PCNL
      with nephrostomy tubes (Group 1), tubeless PCNL with ureteric stent and no
      nephrostomy (Group 2), and totally tubeless PCNL without ureteric catheter or
      nephrostomy (Group 3). Randomization was done at the end of the procedure for
      those patients satisfying the inclusion criteria based on duration of surgery,
      single puncture tract, intraoperative bleeding, stone burden, intact
      pelvicalyceal system, and no residual stones at the end of procedure. The
      outcomes measured were hemoglobin (Hb) drop, hemorrhage, need for blood
      transfusion, pyrexia, urine leak, pain score, analgesic requirement, and duration
      of hospital stay. RESULTS: There was no significant difference in hemorrhage, Hb
      drop, need for blood transfusion, and postoperative pyrexia among the groups. All
      patients except one in the standard group only had variable amount of urinary
      leak. The analgesic requirement and duration of hospital stay attained
      statistical significance in favor of tubeless and totally tubeless groups
      compared to the standard. CONCLUSIONS: Tubeless and totally tubeless PCNL are
      safe and effective method of renal stone management. Totally tubeless PCNL
      significantly reduced postoperative pain and morbidity compared to the tubeless
      method.

PMID- 29021657
TI  - Results of tubularized urethral plate urethroplasty in Megameatus Intact Prepuce.
AB  - OBJECTIVE: The megameatus variant of anterior hypospadias with an intact complete
      foreskin occurs in approximately 1%-3% of hypospadias. Hence, the objective of
      the study was to evaluate the results of tubularized urethral plate urethroplasty
      (TUPU) in megameatus intact prepuce (MIP). MATERIALS AND METHODS: A retrospective
      study (June 1996-June 2015) of MIP from our hypospadias registry was conducted.
      All patients with megameatus, either with an intact prepuce or with one
      previously removed, were included in the study. Case sheets of clinical records,
      investigations, clinical photographs, and videos were reviewed. Patients were
      classified into, glanular, coronal, subcoronal, and distal penile. TUPU were
      done. Patients were called for follow-up at 1, 3, 6, and 12 months
      postoperatively, and then yearly for the assessment of the cosmetic appearance
      and fistula, meatal stenosis, or other complications. RESULTS: Of 1026 patients
      with hypospadias, we identified 13 cases of megameatus variant of hypospadias;
      three of the 13 had been circumcized previously. Glanular approximation was done
      for the one patients of the glanular variant, and another had frenuloplasty.
      These two patients were excluded from the study. Incision in the inner preputial
      skin was closed in 10 patients to have an intact prepuce. Follow-up period varied
      from 6 months to 4 years (median follow-up 21/2 years). None of the patients
      developed complications such as fistula, meatal stenosis, and/or wound
      dehiscence. CONCLUSIONS: Surgical correction of MIP in the era of increased
      cosmetic awareness is justified. Excellent results are obtained with TUPU and
      along with spongioplasty and frenuloplasty because of availability of wide
      urethral plate and well-developed spongiosum in these patients. TUPU should be
      the preferred procedure in cases of MIP.

PMID- 29021658
TI  - Mini access guide to simplify calyceal access during percutaneous
      nephrolithotomy: A novel device.
AB  - INTRODUCTION: A precise puncture of the renal collecting system is the most
      essential step for percutaneous nephrolithotomy (PCNL). There are many techniques
      describing this crucial first step in PCNL including the bull's eye technique,
      triangulation technique, free-hand technique, and gradual descensus technique. We
      describe a novel puncture guide to assist accurate percutaneous needle placement
      during bull's eye technique. METHODS: The mini access guide (MAG) stabilizes the
      initial puncture needle by mounting it on an adjustable multidirectional carrier
      fixed to the patient's skin, which aids in achieving the "bull's eye" puncture.
      It also avoids a direct fluoroscopic exposure of the urologist's hand during the
      puncture. Sixty consecutive patients with solitary renal calculus were randomized
      to traditional hand versus MAG puncture during bull's eye technique of puncture
      and the fluoroscopy time was assessed. RESULTS: The median fluoroscopy screening
      time for traditional free-hand bull's eye and MAG-guided bull's eye puncture
      (fluoroscopic screening time for puncture) was 55 versus 21 s (P = 0.001) and the
      median time to puncture was 80 versus 55 s (P = 0.052), respectively. Novice
      residents also learned puncture technique faster with MAG on simulator.
      CONCLUSION: The MAG is a simple, portable, cheap, and novel assistant to achieve
      successful PCNL puncture. It would be of great help for novices to establish
      access during their learning phase of PCNL. It would also be an asset toward
      significantly decreasing the radiation dose during PCNL access.

PMID- 29021659
TI  - Occult renal cell carcinoma presenting as carcinomatous polyarthritis.
AB  - Carcinomatous polyarthritis (CP) is a rare paraneoplastic disorder which can be
      associated with various solid tumors and can even precede detection of the
      underlying malignancy. A 54-year-old male presented with migratory asymmetric
      inflammatory polyarthritis and high-grade fever for 6 months. On evaluation, he
      was diagnosed to have renal cell carcinoma (RCC). CP as an initial presentation
      of RCC was not described previously.

PMID- 29021660
TI  - 18F-fludeoxyglucose positron emission tomography computed tomography-guided
      diagnosis of prostatic and leptomeningeal tuberculosis.
AB  - Genitourinary tuberculosis contributes to 10%-14% of extrapulmonary TB. Prostate
      tuberculosis is rare and usually found incidentally following transurethral
      resection of the prostate for benign prostatic hyperplasia. We report a case of
      an immunocompetent patient with pyrexia of unknown origin, on evaluation with
      whole-body 18F-fludeoxyglucose positron emission tomography computed tomography
      scan found to have suspicious prostatic primary, with hypermetabolic
      abnormalities involving the brain. Histopathological diagnosis was established as
      multifocal tuberculosis involving prostate, meninges, and intracranial
      tuberculomas.

PMID- 29021661
TI  - Successful renal transplant in a pediatric patient with HIV-associated
      nephropathy.
AB  - HIV-associated nephropathy (HIVAN) is a pathological state of the kidneys due to
      longstanding, uncontrolled HIV infection. With the rapid progression of HIVAN to
      end-stage kidney failure, there is a significant potential for renal
      transplantation to improve the quality of life in these patients. Numerous
      studies have been recently published documenting renal transplantation as a
      primary treatment for HIVAN. With the use of highly active antiretroviral
      therapy, allograft and patient survival rates of HIV-infected persons are nearly
      identical to those who are HIV negative. Our case study documents the successful
      role of renal transplantation in treating HIVAN in a 9-year-old male child.

PMID- 29021662
TI  - Embolized prostatic brachytherapy seeds mimicking acute chest pain syndromes.
AB  - A 59-year-old male with a history of nonobstructive coronary artery disease,
      diabetes mellitus, hypertension, and prostate cancer presented to the hospital
      with 1-day history of pleuritic chest pain. Initial workup for acute coronary
      event was unremarkable. Chest X-ray revealed multiple small radial densities
      which were linear and hyperdense, consistent with embolization of metallic seeds
      to the pulmonary circulation. The patient was noted to have had radioactive
      metallic seeds implanted for prostate cancer 6 months ago. Diagnosis of pulmonary
      embolization of prostatic seeds is challenging as they frequently present with
      chest pain mimicking acute coronary syndromes.

PMID- 29021663
TI  - A game changing LATITUDE: Role of abiraterone plus prednisolone in metastatic
      hormone-sensitive prostate cancer.

PMID- 29021665
TI  - Vertical spinal instability and cervical spondylosis: Is it focal or
      multisegmental?

PMID- 29021664
TI  - Corrigendum to "Indian National Association for Study of the Liver (INASL)
      guidance for antiviral therapy against HCV infection: Update 2016" [J. Clin. Exp.
      Hepatol. 6 (2016) 119-145].
AB  - [This corrects the article DOI: 10.1016/j.jceh.2016.07.001.].

PMID- 29021666
TI  - Short neck, short head, short spine, and short body height - Hallmarks of basilar
      invagination.

PMID- 29021667
TI  - Combined anteroposterior fixation using a titanium cage versus solely posterior
      fixation for traumatic thoracolumbar fractures: A systematic review and meta
      analysis.
AB  - STUDY DESIGN: Systematic review with meta-analysis. OBJECTIVE: Additional
      anterior stabilization might prevent posterior implant failure, but over time,
      the disadvantageous of bone grafts have become evident. The objective of this
      systematic review was to compare risks and advantages of additional anterior
      stabilization with a titanium cage to solely posterior fixation for traumatic
      thoracolumbar fractures. METHODS: An electronic search was performed in the
      literature from 1980 to March 2016. Studies comparing only posterior with
      anteroposterior fixation by means of a titanium cage were included in this study.
      Data extraction and Cochrane risk of bias assessment were done by two independent
      authors. In addition, the PRISMA statement was followed, and the GRADE approach
      was used to present results. RESULTS: Of the 1584 studies, two randomized
      controlled trials (RCTs) and one retrospective cohort study were included in the
      meta-analysis. The RCTs reported evidence of high quality that anteroposterior
      stabilization maintained better kyphosis correction than posterior stabilization
      alone. However, these results were neutralized in the meta-analysis by the cohort
      study. Implant failure was reported by one study, in the posterior group. No
      differences in follow-up visual analog scale scores, neurologic improvement, and
      complications were found. Operation time, blood loss, and hospital stay all
      increased in the anteroposterior group. CONCLUSIONS: Patients with a highly
      comminuted or unstable fracture could benefit from combined anteroposterior
      stabilization with a titanium cage, for some evidence suggests this prevents loss
      of correction. However, large randomized studies still lack. There is a risk of
      cage subsidence, and increased perioperative risks have to be considered when
      choosing the optimal treatment.

PMID- 29021668
TI  - Influence of prevertebral soft tissue swelling on dysphagia after anterior
      cervical discectomy and fusion using a rectangular titanium stand-alone cage.
AB  - BACKGROUND: Postoperative oropharyngeal complications such as dysphagia after
      anterior cervical spine surgery are some of the least discussed surgery-related
      complications. The purpose of this retrospective study is to investigate the
      incidence and possible risk factors for 30-day postoperative dysphagia after
      anterior cervical discectomy and fusion (ACDF). MATERIALS AND METHODS: This study
      included 152 consecutive patients who underwent 1- or 2-level ACDF using a
      rectangular titanium stand-alone cage in our institutes. Surgery-related
      dysphagia early after surgery was analyzed based on hospital charts. Radiological
      evaluation of prevertebral soft tissue swelling (PSTS) was performed by comparing
      plain lateral radiographs of the cervical spine before surgery with those after
      surgery. The percentage of PSTS (%PSTS) was defined by retropharyngeal soft
      tissue diameter divided by vertebral diameter. Positive %PSTS was determined when
      %PSTS exceeded its mean + 2 standard deviations. RESULTS: Twelve patients (7.9%)
      demonstrated prolonged symptoms of dysphagia within 30-day postoperatively. All
      patients eventually demonstrated satisfactory or acceptable recovery late after
      surgery, except one case of hypoglossal nerve palsy. %PSTS was significantly
      highest early after surgery and returned to presurgical levels within 30 days
      after surgery. Statistical analysis suggested that the positive %PSTS at C3 or C4
      level early after surgery was significantly associated with the occurrence of
      postoperative dysphagia. CONCLUSIONS: Although the possible reasons for
      postoperative dysphagia may not only be multifactorial but also be highly surgeon
      dependent, such a complication is still underestimated and needs to be carefully
      resolved. %PSTS appeared to be easy and reliable index to judge the possible risk
      of postoperative dysphagia.

PMID- 29021670
TI  - Preliminary experience with lumbar facet distraction and fixation as treatment
      for lumbar spinal stenosis.
AB  - OBJECTIVES: To assess the properties of facet fixation with the Facet Wedge
      system in patients affected by lumbar spinal stenosis (LSS). SUMMARY OF
      BACKGROUND DATA: Implant of intra-articular spacers is an emerging technique for
      lumbar degenerative disease. METHODS: This study included forty patients (Group
      1) with symptomatic LSS in whom intra-articular spacers have been implanted along
      with microdecompression (MD) of the neural structures. Group 1 has been compared
      with a homogeneous group of patients with LSS treated with MD without intra
      articular spacers implant (Group 2). Clinical findings have been observed
      preoperatively and 3, 6, 12 months postoperatively using dedicated questionnaires
      (Zurich Claudication Questionnaire, visual analog scale, and Oswestry disability
      index). RESULTS: One year following surgical treatment, 87% of the patients
      presented with good improvement of symptoms and 97% referred satisfaction for
      surgery. Overall, patients of Group 1 presented with significantly better
      clinical outcome when compared with the control group (P < 0.01). CONCLUSIONS:
      Intra-articular spacers showed significant and clinically meaningful improvements
      in pain and disability for up to 1 year. These findings need further studies and
      a longer follow-up.

PMID- 29021669
TI  - Is there a correlation between the spinal instability neoplastic score and
      mechanical pain in patients with metastatic spinal cord compression? A
      prospective cohort study.
AB  - INTRODUCTION: The decision for selecting patients for surgical treatment of
      metastatic spinal cord compression (MSCC) is challenging even for experienced
      surgeons. Recently, the spinal instability neoplastic score (SINS) has been
      proposed to help surgeons in the evaluation of spinal stability in the setting of
      spinal metastases. This study aimed to evaluate the correlation between SINS and
      preoperative visual analog scale (VAS), as well as the pre- and post-operative
      association of the VAS and neurological function. METHODS: A prospective cohort
      study was conducted in a tertiary referral cancer center. Seventy-nine patients
      with MSCC were surgically treated from June 2012 to March 2015. Pain status
      before and after surgery was assessed using VAS score, and neurological status
      was evaluated using the American Spine Injury Association Impairment Scale (AIS)
      before and after surgery. Pain was classified as VAS (0-4) none or mild pain; VAS
      (5-8) moderate pain; and VAS (9-10) as severe pain. Neurological function was
      scored as AIS A: Complete deficits, AIS B-D: Incomplete deficits, AIS E:
      Neurologically intact. SINS degrees were classified as 0-6-stable; 7-12
      potentially unstable, and 13-18-unstable. Spearman's correlation coefficient test
      was utilized for correlation between pain and SINS; Chi-square association test
      was utilized for evaluating pre- and post-operative pain and AIS, as well as the
      association between SINS and tumor types. RESULTS: A higher SINS correlates with
      severe mechanical pain preoperatively (rho = 0.38, P = 0.001); surgical procedure
      improved neurological function (P = 0.0001), and decrease pain (P = 0.84).
      Finally, a higher SINS was also associated with osteolytic tumors (P = 0.03).
      CONCLUSIONS: The SINS correlates with mechanical pain. Surgery provides a
      significant improvement in pain and neurological status, especially in patients
      who presented higher SINS scores and some degree of preoperative neurological
      function.

PMID- 29021671
TI  - Atlantoaxial Langerhans cell histiocytosis radiographic characteristics and
      corresponding prognosis analysis.
AB  - BACKGROUND: Langerhans cell histiocytosis (LCH) may affect atlas and axis, and
      there were very few published cases describing a characteristic of LCH of
      atlantoaxial. OBJECTIVE: The objective of the study is to investigate the image
      manifestations of atlantoaxial LCH to improve the in-depth comprehension on it.
      MATERIALS AND METHODS: A retrospective study was done of computed tomography (CT)
      and magnetic resonance imaging in atlas and axis and prognosis was analyzed.
      RESULTS: The study included 41 patients (average age 12.9 years and median age 8
      years) diagnosed with LCH, with 75.6% under 15 years old. Eighty-four lesions of
      LCH were identified including 47 in the atlas and 37 in the axis. The osteolytic
      bone destructions in the atlas and axis were characterized, 22% accompanied by
      sclerotic margins. Thirteen patients had a compression fracture, 11 in the
      lateral mass of the atlas and 2 in the C2 vertebral body. Sixteen and three
      patients had atlantoaxial malalignment and dislocation, respectively. On T2
      weighted images, 68.9% showed iso- or low-signal intensity, 27.6% showed
      hyperintensity signal, and 3.4% showed heterogeneous signal. On postcontrast
      images, 81.9% showed significant enhancement, 12.5% showed moderate enhancement,
      and 6.3% showed mild enhancement. CT reexamination of 14 patients indicated
      atlantoaxial bone destruction relatively repaired in 12 patients. Thirty-three
      patients were a follow-up, 81.8% had no significant symptoms and 18.2% with
      remaining symptoms. CONCLUSIONS: The atlas and axis were affected by LCH, mainly
      in children. The lateral mass was easily affected and compressed, destruction of
      the atlas and axis could lead to atlantoaxial joint instability. The prognosis
      was good in most of the patients.

PMID- 29021672
TI  - The size and shape of the foramen magnum in man.
AB  - BACKGROUND: The foramen magnum (FM) has garnered broad interest across the
      disciplines of anthropology, comparative anatomy, evolutionary biology, and
      clinical sciences. Most studies regarding the structure of the FM in humans have
      been intrapopulation morphometric studies rather than interpopulation morphologic
      studies. The few studies assessing the morphology of the foramen have utilized
      ambiguous and subjective descriptors to describe foraminal shape and are,
      consequently, difficult to reproduce. Therefore, detailed study of FM shape among
      craniofacially and geographically diverse populations through reproducible
      methods is warranted. OBJECTIVES: The aim of this study was to assess intersex
      and interpopulation differences in FM size and shape among diverse populations.
      MATERIALS AND METHODS: The study analyzed 152 FMs of varied sex and race via
      traditional and geometric morphometric methods. RESULTS AND CONCLUSIONS: The
      study demonstrates that, within each distinct population, the size of the FM is
      significantly larger in males than in females; however, there are no significant
      differences in the shapes of the foramina between sexes. However, when comparing
      different populations to one another, there are significant differences with
      regard to both the size and shape of the FM. This study also presents a new model
      of FM ontogeny. Specifically, the growth occurring between the anterior and
      posterior foraminal boundaries before 5 years of age predicts the ultimate shape
      of the adult FM.

PMID- 29021673
TI  - Risk factors for 30-day outcomes in elective anterior versus posterior cervical
      fusion: A matched cohort analysis.
AB  - OBJECTIVE: Cervical spine fusion is the preferred treatment modality for a
      variety of degenerative and/or myelopathic disorders. Surgeons select between two
      approaches (anterior or posterior cervical fusion [ACF; PCF]) based on
      pathoanatomical features and spinal levels involved. Complications and outcome
      profiles between the approaches following elective surgery have not been
      systematically investigated. METHODS: Adult patients undergoing elective ACF or
      PCF were extracted from the American College of Surgeons National Surgical
      Quality Improvement Program years 2011-2014. Five hundred twenty-eight patients
      (264 ACF and 264 PCF) were matched 1:1 by age, sex, functional status, vertebral
      levels operated, and the American Society of Anesthesiologists classification.
      Multivariable regression was performed by surgical approach for operation time,
      complications, hospital length of stay (HLOS), and discharge destination,
      controlling for body mass index and comorbidities. Mean differences (B), odds
      ratios (ORs), and 95% confidence intervals (CIs) are reported. RESULTS: Compared
      to ACF, PCF was associated with increased odds of blood transfusions >1 unit (OR
      = 4.31, 95% CI [1.18-15.75]; P = 0.027) and failure to discharge to home (OR =
      3.68 [2.17-6.25]; P < 0.001), and increased mean HLOS (B = 1.72 days [1.19-2.26];
      P < 0.001). No differences in operation time, other complications, or reoperation
      rates were found by surgical approach. CONCLUSIONS: In a matched cohort analysis
      by age, sex, functional and physical status, and vertebral levels, elective PCF
      is associated with increased HLOS and increased likelihood of failing to
      discharge to home compared to ACF without increased risk of 30-day complications.
      Increased blood transfusion volume is noted for patients undergoing PCF. Future
      prospective studies are warranted.

PMID- 29021674
TI  - The efficacy of sagittal cervical spine subtyping: Investigating radiological
      classification methods within 150 asymptomatic participants.
AB  - AIMS: The aim of this study is to (1) compare and contrast cervical subtype
      classification methods within an asymptomatic population, and (2) identify inter
      methodological consistencies and describe examples of inconsistencies that have
      the potential to affect subtype classification and clinical decision-making.
      METHODS: A total of 150 asymptomatic 18-30-year-old participants met the strict
      inclusion criteria. An erect neutral lateral radiograph was obtained using
      standard procedures. The Centroid, modified Takeshima/Herbst methods and the
      relative rotation angles in cases of nonagreement were used to determine subtype
      classifications. Cohen's kappa coefficient (kappa) was used to assess the level
      of agreement between the two methods. RESULTS: Nonlordotic classifications
      represented 66% of the cohort. Subtype classification identified the cohort as,
      lordosis (51), straight (37), global kyphosis (30), sigmoidal (13), and reverse
      sigmoidal (RS) (19). Cohen's kappa coefficient indicated that there was only a
      moderate level of agreement between methods (kappa = 0.531). Methodological
      agreement tended to be higher within the lordotic and global kyphotic subtypes
      whereas, straight, sigmoidal, and RS subtypes demonstrated less agreement.
      CONCLUSION: This is the first study of its type to compare and contrast cervical
      classification methods. Subtypes displaying predominantly extended or flexed
      segments demonstrated higher levels of agreement. Our findings highlight the need
      for establishing a standardized multi-method approach to classify sagittal
      cervical subtypes.

PMID- 29021675
TI  - Surgical treatment of bilateral nondisplaced isthmic lysis by interlaminar
      fixation device.
AB  - STUDY DESIGN: Spondylolysis is a defect in the portion of pars interarticularis.
      The latter affects approximately 6% of the population. It is caused by repetitive
      trauma in hyperextension. Low back pain is the most common symptom. METHODS: We
      implanted interspinous process devices in 12 patients with isthmic lysis without
      spondylolisthesis for low back pain. The purpose of the surgery was to conduct a
      minimally invasive procedure. RESULTS: In eight cases, patients became
      asymptomatic. In two cases, there has been a considerable improvement. In two
      cases, no change had been noted. CONCLUSION: This good result motivates us to
      consider this approach a part of therapeutic arsenal for some cases of
      spondylolysis.

PMID- 29021677
TI  - A very rare spinal cord tumor primary spinal oligodendroglioma: A review of sixty
      cases in the literature.
AB  - LITERATURE REVIEW: In this study, we evaluated a case of primary spinal
      oligodendroglioma (PSO) with a rare localization between L3 and S2, and also
      examined sixty cases in the literature in terms of demographic characteristics,
      clinical, radiological, and histopathological characteristics, and treatment
      planning. A case of PSO has been presented, and the relevant literature between
      1931 and 2016 was reviewed. A total of 57 papers regarding PSO were found and
      utilized in this review. The main treatment options include radical surgical
      excision with neuromonitoring, followed by radiotherapy. Despite these treatment
      protocols, the relapse rate is high, and treatment does not significantly prolong
      survival. Oligodendrogliomas are rare among the primary spinal cord tumors.
      Oligodendrogliomas are predominantly found in the cervical spinal cord, thoracic
      spinal cord, or junctions during childhood and adulthood. Extension to the sacral
      region, inferior to the Conus, is very rare. Furthermore, of the sixty cases in
      the literature, the case we present here is the first to be reported in this
      particular age group. These localizations usually occur in the pediatric age
      group and after relapses. While for a limited number of cases the
      oligodendroglioma initiates in the thoracic region and reaches as far as L2, we
      encountered a case of an oligodendroglioma within the range of L3 to S2. Clinical
      findings are observed in accordance with location, and magnetic resonance imaging
      is the gold standard for diagnosis.

PMID- 29021678
TI  - Surgical planning for cervical deformity based on a 3D model.
AB  - The treatment of fixed cervical deformity is complex, but the principles guiding
      its correction remain the same as in deformity of other spinal regions, with the
      goal of deformity correction that results in a solid fusion with adequate
      decompression of the neural elements. In these challenging cases, osteotomies are
      necessary to mobilize the rigid spine and to obtain the desired correction, but
      they can be associated with increased risk of complications. Therefore, careful
      preoperative planning and a complete understanding of the anatomic variations
      allow patient-tailored approaches with and case specific techniques for the
      optimal and safe treatment of a variety of complex cervical deformities. We
      present a case report with a complex spinal deformity where a 3D model was used
      for surgical strategy that allowed us to "simulate" the osteotomies and get a
      better correction of the cervical deformity.

PMID- 29021676
TI  - "Stealth cranioplasty:" A novel endeavor for symptomatic adult Chiari I patients
      with syringomyelia: Technical note, appraisal, and philosophical considerations.
AB  - AIM AND OBJECTIVE: In this article, we describe a novel technique of
      reconstruction of posterior fossa by cranioplasty with use of preshaped titanium
      mesh following posterior fossa decompression (PFD) for Chiari malformation type I
      (CMI) with syringomyelia (SM) in symptomatic adults. MATERIALS AND METHODS:
      Eleven patients underwent limited PFD and expansive cranioplasty with preshaped
      titanium mesh, what we term as "Stealth Cranioplasty" (SCP), following arachnoid
      preserving duraplasty (APD) and hexagonal tenting of the duraplasty with the
      cranioplasty (HTDC) for the management of symptomatic adult CMI with SM. All
      these patients had syringes extending from 3 to >10 vertebral levels. RESULTS:
      Seven male and four female symptomatic CMI adult patients, between age ranges of
      22 and 44 years (mean 29.45 years), presented with different neurological
      symptoms related to CMI and SM for 6-84 months (mean 37.09 months). All the
      patients underwent PFD, APD followed by SCP and HTDC and were followed up for 7
      54 months (mean 35.90 months). Of 11 patients, 8 patients improved according to
      the Chicago Chiari Outcome Scale (CCOS) with score of 13-15 while 3 patients
      remained unchanged with CCOS of 12, and there was no worsening. There was no
      complication related to Chiari surgery in any of the patients. All the patients
      had good reestablishment of cisterna magna. Two patients had marked reduction of
      syrinx while eight patients had moderate-to-mild reduction and one patient had no
      change of syrinx. None of the patients needed redo surgery. CONCLUSION: SCP is an
      effective, fruitful, and cost-effective technique for the management of
      symptomatic adult CMI with SM. This technique has the advantages of preventing
      complications and recurrences in addition to the improvement of symptoms by
      addressing the basic pathology.

PMID- 29021679
TI  - A rare case of a vertebrojugular arteriovenous fistula: A case report and review
      of literature.
AB  - Vertebrojugular fistulas have been described in the literature associated with
      blunt or penetrating injury and iatrogenic or spontaneous development. Its
      presentation may be broad and may include symptoms of radiculopathy,
      vertebrobasilar insufficiency, tinnitus, and bruit. However, so far, no direct
      cardiac complications had been reported. Here, we describe a case of an 86-year
      old female who suffered a C5 vertebral fracture secondary to a ground-level fall
      that was initially treated conservatively due to the onset of new severe atrial
      fibrillation. However, the patient was later on taken to surgery due to
      progressive neurologic deterioration. Intraoperative complications led to the
      diagnosis of a vertebral-jugular fistula that was successfully embolized. The
      effective obliteration of the fistulae led to the recovery of both neurologic and
      cardiac symptoms.

PMID- 29021680
TI  - Nondysraphic cervicomedullary intramedullary lipoma.
AB  - Spinal cord lipomas are usually associated with spinal dysraphism and is most
      common in lumbosacral region. Spinal intradural lipoma is a rare condition
      accounting for less than 1% of spinal cord tumours and is most prevalent in
      cervicodorsal region. Intramedullary spinal cord lipoma of cervical spine not
      associated with spinal dysraphism is one of the rarest lesions. They usually
      present insidiously with slowly progressive myelopathic deficits. We present a
      case of nondysraphic intramedullary spinal cord lipoma with exophytic component
      and intracranial extension. A 30 year male patient presented with wasting of
      muscles of left shoulder and left forearm with resultant weakness for last two
      months and myelopathic signs. Magnetic resonance imaging revealed a T1
      hyperintense , T2 hypointense lesion on the dorsal aspect of cervical spinal cord
      with intracranial extension and exophytic component. There was no contrast
      enhancement, fat suppression image indicated a lipoma. The patient underwent
      cervical laminectomy with foramen magnum decompression with subtotal resection of
      intramedullary lipoma. Histopathology examination confirmed the diagnosis of
      lipoma. Subtotal resection of intramedullary lipoma is a reasonable and
      acceptable surgical option considering the benign nature of lesion and high
      probability of neurological deterioration due to dense adhesion between lipoma
      and neural tissue.

PMID- 29021681
TI  - Acute spinal cord compression caused by atypical vertebral hemangioma.
AB  - Vertebral hemangioma is common, benign lesion that occurs mostly in the body of
      vertebral bones and is mostly asymptomatic although they may occasionally extend
      into the posterior elements. An isolated location in the neural arch of vertebrae
      is extremely rare. An acute spinal cord compression by an exceptional hemangioma
      involving spinous process of the seventh thoracic vertebra and respecting
      vertebral body in a 40-year-old woman is reported. On magnetic resonance imaging
      of the spine, the lesion was hypointense on T1-weighted image, hyperintense on T2
      weited image, and enhancing avidly, causing compression of spinal cord. Our case
      is exceptional by the rapidly character of symptom installation and by atypical
      and elective involvement of spinous process.

PMID- 29021682
TI  - Spontaneous regression of retro-odontoid post traumatic cicatrix following
      occipitocervical fixation.
AB  - This case report describes a patient who presented with myelopathy secondary to a
      large retro-odontoid post traumatic cicatrix. The objective of this study was to
      discuss the clinical presentation, pathogenesis, imaging, and surgical management
      of pseudoarthrosis tissue mass associated with odontoid nonunion. Atlantoaxial
      subluxation (AAS) has been widely reported in patients with rheumatoid arthritis.
      AAS leads to repeated cycles of partial tear and repair of ligaments around the
      altantoaxial complex, resulting in the formation of periodontoid mass
      (pseudotumor). It is thought that formation of retro-odontoid post traumatic mass
      (cicatrix), in certain cases of odontoid fracture, is because of similar
      pathology. This is a retrospective review of case note. Here, the patient
      underwent posterior decompression through a C1-C2 laminectomy and
      occipitocervical (C0-C4) fusion with instrumentation, which resulted in dramatic
      improvement in his symptoms and spontaneous regression of retro-odontoid post
      traumatic cicatrix. We have described an interesting and a rare case of a large
      pseudoarthrosis tissue mass associated with odontoid nonunion, which regressed
      following stand-alone posterior instrumentation. To the best of our knowledge,
      only a handful of such cases of spontaneous regression of retro-odontoid post
      traumatic cicatrix following occipitocervical fixation have been described in
      literature, and our case adds to the growing list of such cases and may help in
      understanding the natural history of the disease process one day. Although rare,
      post traumatic cicatrix should be considered as a differential diagnosis of
      enhancing retro-odontoid mass, especially if there is any history of cervical
      spine trauma.

PMID- 29021683
TI  - Aarskog-Scott syndrome: An unusual cause of scoliosis.
AB  - A 16-year-old boy who had been diagnosed previously as Aarskog-Scott syndrome
      (AAS), referred to our clinic with shoulder asymmetry for 1 year. Results of
      spine examination showed a 52 degrees  right thoracic curve at T3-T11. Surgery
      was planned, and T1-L1 posterior instrumentation and fusion were performed. After
      surgery, satisfactory correction was achieved, and during 10 years follow-up, the
      patient had no complaints. AAS is a X-linked genetic disorder with facial,
      genital, and skeletal manifestations. Scoliosis is not reported as a typical
      finding of AAS, and there is no reported case in the English literature. Due to
      mutation affecting the developing skeleton tissue, spinal deformities may
      develop. In our case, concave side fusion was seen at the deformity. Although we
      do not know any specific pattern of the scoliotic deformity of this syndrome,
      surgical correction of the deformity can be difficult because of the premature
      fusion at these levels.

PMID- 29021684
TI  - Use of C2 vertebroplasty and stereotactic radiosurgery for treatment of lytic
      metastasis of the odontoid process.
AB  - Improvements in cancer therapy have led to increased patient survival times in
      spite of metastatic spinal disease in many forms of cancer. Conventional
      treatment methods often employ radiotherapy with or without surgery depending on
      the neurological status, mechanical instability, and the extent of tumor.
      Percutaneous vertebroplasty as well as stereotactic radiosurgery (SRS) have
      arisen as common modalities of treatment of spinal metastasis in which
      neurological compromise or spinal instability and deformity is not of significant
      concern. These treatments, when used in combination, have been shown to provide
      early pain relief and effective tumor control while avoiding surgical resection,
      fixation, and lengthy recovery times. We present a case unique in the literature
      for the use of this combination treatment for tumors of the C2 vertebral body.
      While limited in application to patients without overt atlantoaxial instability
      or significant spinal canal compromise, we believe it provides a significant
      benefit in decreasing morbidity and improving early adherence to systemic
      therapy.

PMID- 29021686
TI  - Hydatid disease of the spine: A rare case.

PMID- 29021685
TI  - Idiopathic thoracic transdural intravertebral spinal cord herniation.
AB  - Idiopathic spinal cord herniation is a rare and often missed cause of thoracic
      myelopathy. The clinical presentation and radiological appearance is inconsistent
      and commonly confused with a dorsal arachnoid cyst and often is a misdiagnosed
      entity. While ventral spinal cord herniation through a dural defect has been
      previously described, intravertebral herniation is a distinct entity and
      extremely rare. We present the case of a 70-year old man with idiopathic thoracic
      transdural intravertebral spinal cord herniation and discuss the clinico
      radiological presentation, pathophysiology and operative management along with a
      review the literature of this unusual entity.

PMID- 29021687
TI  - "Formation" of Chiari "malformation:" Nature's philosophical way of adaptation.

PMID- 29021689
TI  - Applications of molecular markers in the discrimination of Panax species and
      Korean ginseng cultivars (Panax ginseng).
AB  - The development of molecular markers is one of the most useful methods for
      molecular breeding and marker-based molecular associated selections. Even though
      there is less information on the reference genome, molecular markers are
      indispensable tools for determination of genetic variation and identification of
      species with high levels of accuracy and reproducibility. The demand for
      molecular approaches for marker-based breeding and genetic discriminations in
      Panax species has greatly increased in recent times and has been successfully
      applied for various purposes. However, owing to the existence of diverse
      molecular techniques and differences in their principles and applications, there
      should be careful consideration while selecting appropriate marker types. In this
      review, we outline the recent status of different molecular marker applications
      in ginseng research and industrial fields. In addition, we discuss the basic
      principles, requirements, and advantages and disadvantages of the most widely
      used molecular markers, including restriction fragment length polymorphism,
      random amplified polymorphic DNA, sequence tag sites, simple sequence repeats,
      and single nucleotide polymorphisms.

PMID- 29021688
TI  - Role of ginsenosides, the main active components of Panax ginseng, in
      inflammatory responses and diseases.
AB  - Panax ginseng is one of the most universally used herbal medicines in Asian and
      Western countries. Most of the biological activities of ginseng are derived from
      its main constituents, ginsenosides. Interestingly, a number of studies have
      reported that ginsenosides and their metabolites/derivatives-including
      ginsenoside (G)-Rb1, compound K, G-Rb2, G-Rd, G-Re, G-Rg1, G-Rg3, G-Rg5, G-Rh1, G
      Rh2, and G-Rp1-exert anti-inflammatory activities in inflammatory responses by
      suppressing the production of proinflammatory cytokines and regulating the
      activities of inflammatory signaling pathways, such as nuclear factor-kappaB and
      activator protein-1. This review discusses recent studies regarding molecular
      mechanisms by which ginsenosides play critical roles in inflammatory responses
      and diseases, and provides evidence showing their potential to prevent and treat
      inflammatory diseases.

PMID- 29021690
TI  - Effect of Korean Red Ginseng in chronic liver disease.
AB  - Chronic liver disease, one of the most common diseases, typically arises from
      nonalcoholic fatty liver disease, alcoholic liver disease, chronic viral
      hepatitis, or hepatocellular carcinoma. Therefore, there is a pressing need for
      improved treatment strategies. Korean Red Ginseng has been known to have positive
      effects on liver disease and liver function. In this paper, we summarize the
      current knowledge on the beneficial effects of Korean Red Ginseng on chronic
      liver disease, a condition encompassing nonalcoholic fatty liver disease,
      alcoholic liver disease, chronic viral hepatitis, and hepatocellular carcinoma,
      as supported by experimental evaluation and clinical investigation.

PMID- 29021691
TI  - Photoprotective effects of topical ginseng leaf extract using Ultraflo L against
      UVB-induced skin damage in hairless mice.
AB  - BACKGROUND: Abnormal activation of matrix metalloproteinases (MMPs) plays an
      important role in UV-induced wrinkle formation, which is a major dermatological
      problem. This formation occurs due to the degeneration of the extracellular
      matrix (ECM). In this study, we investigated the cutaneous photoprotective
      effects of Ultraflo L treated ginseng leaf (UTGL) in hairless mice. METHODS: SKH
      1 hairless mice (6 weeks of age) were randomly divided into four groups (8
      mice/group). UTGL formulation was applied topically to the skin of the mice for
      10 weeks. The normal control group received nonvehicle and was not irradiated
      with UVB. The UV control (UVB) group received nonvehicle and was exposed to
      gradient-UVB irradiation. The groups (GA) receiving topical application of UTGL
      formulation were subjected to gradient-UVB irradiation on 0.5 mg/cm2 [GA-low (GA
      L)] and 1.0 mg/cm2 [(GA-high (GA-H)] of dorsal skin area, respectively. RESULTS:
      We found that topical treatment with UTGL attenuated UVB-induced epidermal
      thickness and impairment of skin barrier function. Additionally, UTGL suppressed
      the expression of MMP-2, -3, and -13 induced by UVB irradiation. Our results show
      that topical application of UTGL protects the skin against UVB-induced damage in
      hairless mice and suggest that UTGL can act as a potential agent for preventing
      and/or treating UVB-induced photoaging. CONCLUSION: UTGL possesses sunscreen
      properties and may exhibit photochemoprotective activities inside the skin of
      mice. Therefore, UTGL could be used as a potential therapeutic agent to protect
      the skin against UVB-induced photoaging.

PMID- 29021692
TI  - Cytohistological study of the leaf structures of Panax ginseng Meyer and Panax
      quinquefolius L.
AB  - BACKGROUND: Both Panax ginseng Meyer and Panax quinquefolius are obligate shade
      loving plants whose natural habitats are broadleaved forests of Eastern Asia and
      North America. Panax species are easily damaged by photoinhibition when they are
      exposed to high temperatures or insufficient shade. In this study, a
      cytohistological study of the leaf structures of two of the most well-known Panax
      species was performed to better understand the physiological processes that limit
      photosynthesis. METHODS: Leaves of ginseng plants grown in soil and hydroponic
      culture were sectioned for analysis. Leaf structures of both Panax species were
      observed using a light microscope, scanning electron microscope, and transmission
      electron microscope. RESULTS: The mesostructure of both P. ginseng and P.
      quinquefolius frequently had one layer of noncylindrical palisade cells and three
      or four layers of spongy parenchymal cells. P. quinquefolius contained a similar
      number of stomata in the abaxial leaf surface but more tightly appressed enlarged
      grana stacks than P. ginseng contained. The adaxial surface of the epidermis in
      P. quinquefolius showed cuticle ridges with a pattern similar to that of P.
      ginseng. CONCLUSION: The anatomical leaf structure of both P. ginseng and P.
      quinquefolius shows that they are typical shade-loving sciophytes. Slight
      differences in chloroplast structure suggests that the two different species can
      be authenticated using transmission electron microscopy images, and light
      resistant cultivar breeding can be performed via controlling photosynthesis
      efficiency.

PMID- 29021693
TI  - A refined Panax ginseng karyotype based on an ultra-high copy 167-bp tandem
      repeat and ribosomal DNAs.
AB  - BACKGROUND: Panax ginseng Meyer (Asian ginseng) has a large nuclear genome size
      of > 3.5 Gbp in haploid genome equivalent of 24 chromosomes. Tandem repeats (TRs)
      occupy significant portions of the genome in many plants and are often found in
      specific genomic loci, making them a valuable molecular cytogenetic tool in
      discriminating chromosomes. In an effort to understand the P. ginseng genome
      structure, we characterized an ultrahigh copy 167-bp TR (Pg167TR) and explored
      its chromosomal distribution as well as its utility for chromosome
      identification. METHODS: Polymerase chain reaction amplicons of Pg167TR were
      labeled, along with 5S and 45S rDNA amplicons, using a direct nick-translation
      method. Direct fluorescence in situ hybridization (FISH) was used to analyze the
      chromosomal distribution of Pg167TR. RESULTS: Recently, we reported a method of
      karyotyping the 24 chromosome pairs of P. ginseng using rDNA and DAPI (4',6
      diamidino-2-phenylindole) bands. Here, a unique distribution of Pg167TR in all 24
      P. ginseng chromosomes was observed, allowing easy identification of individual
      homologous chromosomes. Additionally, direct labeling of 5S and 45S rDNA probes
      allowed the identification of two additional 5S rDNA loci not previously
      reported, enabling the refinement of the P. ginseng karyotype. CONCLUSION:
      Identification of individual P. ginseng chromosomes was achieved using Pg167TR
      FISH. Chromosome identification is important in understanding the P. ginseng
      genome structure, and our method will be useful for future integration of genetic
      linkage maps and genome scaffold anchoring. Additionally, it is a good tool for
      comparative studies with related species in efforts to understand the evolution
      of P. ginseng.

PMID- 29021694
TI  - Korean Red Ginseng extract induces angiogenesis through activation of
      glucocorticoid receptor.
AB  - BACKGROUND: Our previous studies have demonstrated that ginsenoside-Rg1 can
      promote angiogenesis in vitro and in vivo through activation of the
      glucocorticoid receptor (GR). Furthermore, microRNA (miRNA) expression profiling
      has shown that Rg1 can modulate the expression of a subset of miRNAs to induce
      angiogenesis. Moreover, Rb1 was shown to be antiangiogenic through activation of
      a different pathway. These studies highlight the important functions of miRNAs on
      ginseng-regulated physiological processes. The aim of this study was to determine
      the angiogenic properties of Korean Red Ginseng extract (KGE). METHODS AND
      RESULTS: Combining in vitro and in vivo data, KGE at 500 MUg/mL was found to
      induce angiogenesis. According to the miRNA sequencing, 484 differentially
      expressed miRNAs were found to be affected by KGE. Among them, angiogenic-related
      miRNAs; miR-15b, -23a, -214, and -377 were suppressed by KGE. Meanwhile, their
      corresponding angiogenic proteins were stimulated, including vascular endothelial
      growth factor, vascular endothelial growth factor receptor-2, endothelial nitric
      oxide synthase, and MET transmembrane tyrosine kinase. The miRNAs-regulated
      signaling pathways of KGE were then found by Cignal 45-Pathway Reporter Array,
      proving that KGE could activate GR. CONCLUSION: KGE was found capable of inducing
      angiogenesis both in vivo and in vitro models through activating GR. This study
      provides a valuable insight into the angiogenic mechanisms depicted by KGE in
      relation to specific miRNAs.

PMID- 29021695
TI  - Chemical and bioactive comparison of flowers of Panax ginseng Meyer, Panax
      quinquefolius L., and Panax notoginseng Burk.
AB  - BACKGROUND: Although flowers of Panax ginseng Meyer (FPG), Panax quinquefolius L.
      (FPQ), and Panax notoginseng Burk. (FPN) have been historically used as both
      medicine and food, each is used differently in practice. METHODS: To investigate
      the connection between components and enhancing immunity activity of FPG, FPQ,
      and FPN, a method based on a rapid LC coupled with quadrupole time-of-flight MS
      and immunomodulatory activity study evaluated by a carbon clearance test were
      combined. RESULTS: According to quantitative results, the ratio of the total
      content of protopanaxatiol-type ginsenosides to protopanaxadiol-type ginsenosides
      in FPN was 0, but ranged from 1.10 to 1.32 and from 0.23 to 0.35 in FPG and FPQ,
      respectively. The ratio of the total content of neutral ginsenosides to the
      corresponding malonyl-ginsenosides in FPN (5.52 +/- 1.33%) was higher than FPG
      (3.2 +/- 0.64%) and FPQ (2.39 +/- 0.57%). The colorimetric analysis showed the
      content of total ginsenosides in FPQ, FPG, and FPN to be 13.75 +/- 0.60%, 17.45
      +/- 0.42%, and 12.45 +/- 1.77%, respectively. The carbon clearance assay
      indicated that the phagocytic activity of FPG and FPQ was higher than that of
      FPN. A clear discrimination among FPG, FPQ, and FPN was observed in the principal
      component analysis score plots. Seven compounds were confirmed to contribute
      strongly by loading plots, which may be the cause of differences in efficacy.
      CONCLUSION: This study provides basic information about the chemical and
      bioactive comparison of FPG, FPQ, and FPN, indicating that protopanaxtriol-type
      ginsenosides and malonyl-ginsenosides may play a key role in their enhancing
      immunity properties.

PMID- 29021696
TI  - Antiviral activity of 20(R)-ginsenoside Rh2 against murine gammaherpesvirus.
AB  - BACKGROUND: Ginsenosides are the major components of Panax ginseng Meyer, an
      herbal medicine used for the treatment of various diseases. Different
      ginsenosides contribute to the biological properties of ginseng, such as
      antimicrobial, anticancer, and immunomodulatory properties. In this study, we
      investigated the antiviral effects of 15 ginsenosides and compound K on
      gammaherpesvirus. METHODS: The antiviral activity of ginsenosides was examined
      using the plaque-forming assay and by analyzing the expression of the lytic gene.
      RESULTS: 20(R)-Ginsenoside Rh2 inhibited the replication and proliferation of
      murine gammaherpesvirus 68 (MHV-68), and its half-maximal inhibitory
      concentration (IC50) against MHV-68 was estimated to be 2.77 MUM. In addition,
      20(R)-ginsenoside Rh2 inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)
      induced lytic replication of human gammaherpesvirus in the Kaposi's sarcoma
      associated herpesvirus (KSHV)-positive cell line BC3. CONCLUSION: Our results
      indicate that 20(R)-ginsenoside Rh2 can inhibit the replication of mouse and
      human gammaherpesviruses, and thus, has the potential to treat gammaherpesvirus
      infection.

PMID- 29021697
TI  - Chronic saponin treatment attenuates damage to the pancreas in chronic alcohol
      treated diabetic rats.
AB  - BACKGROUND: Chronic heavy alcohol consumption may raise the risk of developing
      type 2 diabetes mellitus. Saponins inhibit apoptosis of pancreatic islet cells
      and reduce lipid parameters. The present study was designed to investigate the
      effect of saponin on chronic ethanol-treated diabetic rats. METHODS: Long-Evans
      Tokushima Fatty (LETO) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats were
      pair-fed a Lieber-DeCarli diet with and without 5% ethanol for 12 wks. Two weeks
      after starting the pair-feeding with the Lieber-DeCarli diet, intraperitoneal
      injection of saponin was performed for 10 wks. To perform the experiments, rats
      were divided as follows: LETO-Control (LC), LETO-Ethanol (LE), LETO-Ethanol
      Saponin (LES), OLETF-Control (OC), OLETF-Ethanol (OE), and OLETF-Ethanol-Saponin
      (OES). RESULTS: The weights of epididymal and mesenteric fat tissue in LES and
      OES rats were the lightest from among the LETO and OLETF groups, respectively.
      The secretion of alanine aminotransferase and cholesterol in OES rats decreased
      significantly compared to their secretion in OC and OE rats, respectively. The
      islets of the pancreas in LE and OE rats showed clean, unclear, and smaller
      morphology compared to those of LC, LES, OC, and OES rats. In addition, the
      expression of insulin in the islets of the pancreas in LC, LES, OC, and OES rats
      was higher than in LE and OE rats. CONCLUSION: Saponin may not only be helpful in
      alleviating the rapid progress of diabetes due to chronic alcohol consumption in
      diabetic patients, but may also show potential as an antidiabetic drug candidate
      for diabetic patients who chronically consume alcohol.

PMID- 29021698
TI  - Nonsaponin fractions of Korean Red Ginseng extracts prime activation of NLRP3
      inflammasome.
AB  - BACKGROUND: Korean Red Ginseng extracts (RGE) have been suggested as effective
      immune modulators, and we reported that ginsenosides possess anti-inflammasome
      properties. However, the properties of nonsaponin components of RGE have not been
      well studied. METHODS: To assess the roles of nonsaponin fractions (NS) in NLRP3
      inflammasome activation, we treated murine macrophages with or without first or
      second inflammasome activation signals with RGE, NS, or saponin fractions (SF).
      The first signal was nuclear factor kappa-light-chain-enhancer of activated B
      cells (NF-kappaB)-mediated transcription of pro-interleukin (IL)-1beta and NLRP3
      while the second signal triggered assembly of inflammasome components, leading to
      IL-1beta maturation. In addition, we examined the role of NS in IL-6 production
      and IL-1beta maturation in mice. RESULTS: NS induced IL-1beta and NLRP3
      transcription via toll-like receptor 4 signaling, whereas SF blocked expression.
      During the second signal, SF attenuated NLRP3 inflammasome activation while NS
      did not. Further, NS-injected mice presented increased IL-1beta maturation and IL
      6 production. CONCLUSION: SF and NS of RGE play differential roles in the NLRP3
      inflammasome activation. Hence, RGE can be suggested as an NLRP3 inflammasome
      modulator.

PMID- 29021699
TI  - Evaluation of ginsenoside bioconversion of lactic acid bacteria isolated from
      kimchi.
AB  - BACKGROUND: Panax ginseng is a physiologically active plant widely used in
      traditional medicine that is characterized by the presence of ginsenosides. Rb1,
      a major ginsenoside, is used as the starting material for producing ginsenoside
      derivatives with enhanced pharmaceutical potentials through chemical, enzymatic,
      or microbial transformation. METHODS: To investigate the bioconversion of
      ginsenoside Rb1, we prepared kimchi originated bacterial strains Leuconostoc
      mensenteroides WiKim19, Pediococcus pentosaceus WiKim20, Lactobacillus brevis
      WiKim47, Leuconostoc lactis WiKim48, and Lactobacillus sakei WiKim49 and analyzed
      bioconversion products using LC-MS/MS mass spectrometer. RESULTS: L.
      mesenteroides WiKim19 and Pediococcus pentosaceus WiKim20 converted ginsenoside
      Rb1 into the ginsenoside Rg3 approximately five times more than Lactobacillus
      brevis WiKim47, Leuconostoc lactis WiKim48, and Lactobacillus sakei WiKim49. L
      mesenteroides WIKim19 showed positive correlation with beta-glucosidase activity
      and higher transformation ability of ginsenoside Rb1 into Rg3 than the other
      strains whereas, P. pentosaceus WiKim20 showed an elevated production of Rb3 even
      with lack of beta-glucosidase activity but have the highest acidity among the
      five lactic acid bacteria (LAB). CONCLUSION: Ginsenoside Rg5 concentration of
      five LABs have ranged from ~2.6 MUg/mL to 6.5 MUg/mL and increased in accordance
      with the incubation periods. Our results indicate that the enzymatic activity
      along with acidic condition contribute to the production of minor ginsenoside
      from lactic acid bacteria.

PMID- 29021700
TI  - Ginsenoside Rg12, a new dammarane-type triterpene saponin from Panax ginseng
      root.
AB  - BACKGROUND: Panax ginseng has been used as Korean medicine for various diseases.
      It has antioxidant, hypotensive, sedative, analgesic, and endocrine activities.
      Dammarane-type triterpenes from the plant have various beneficial effects.
      METHODS: A dammarane-type triterpene saponin was isolated from P. ginseng root
      through chromatography such as repeated column chromatography and medium pressure
      liquid chromatography. RESULTS AND CONCLUSION: New dammarane-type triterpene
      saponin was isolated for the first time from nature. The structure was elucidated
      as ginsenoside Rg12 (1) based on spectral data. There may be good materials from
      P. ginseng for the development of industrial applications such as nutraceutical,
      pharmaceutical, and cosmeceutical purposes.

PMID- 29021701
TI  - Using reverse docking to identify potential targets for ginsenosides.
AB  - BACKGROUND: Ginsenosides are the main ingredients of ginseng, which, in
      traditional Eastern medicine, has been claimed to have therapeutic values for
      many diseases. In order to verify the effects of ginseng that have been
      empirically observed, we utilized the reverse docking method to screen for target
      proteins that are linked to specific diseases. METHODS: We constructed a target
      protein database including 1,078 proteins associated with various kinds of
      diseases, based on the Potential Drug Target Database, with an added list of
      kinase proteins. We screened 26 kinds of ginsenosides of this target protein
      database using docking. RESULTS: We found four potential target proteins for
      ginsenosides, based on docking scores. Implications of these "hit" targets are
      discussed. From this screening, we also found four targets linked to possible
      side effects and toxicities, based on docking scores. CONCLUSION: Our method and
      results can be helpful for finding new targets and developing new drugs from
      natural products.

PMID- 29021702
TI  - Biotransformation of Panax ginseng extract by rat intestinal microflora:
      identification and quantification of metabolites using liquid chromatography
      tandem mass spectrometry.
AB  - BACKGROUND: In general, after Panax ginseng is administered orally, intestinal
      microbes play a crucial role in its degradation and metabolization process.
      Studies on the metabolism of P. ginseng by microflora are important for obtaining
      a better understanding of their biological effects. METHODS: In vitro
      biotransformation of P. ginseng extract by rat intestinal microflora was
      investigated at 37 degrees C for 24 h, and the simultaneous determination of the
      metabolites and metabolic profile of P. ginseng saponins by rat intestinal
      microflora was achieved using LC-MS/MS. RESULTS: A total of seven ginsenosides
      were detected in the P. ginseng extract, including ginsenosides Rg1, Re, Rf, Rb1,
      Rc, Rb2, and Rd. In the transformed P. ginseng samples, considerable amounts of
      deglycosylated metabolite compound K and Rh1 were detected. In addition, minimal
      amounts of deglycosylated metabolites (ginsenosides Rg2, F1, F2, Rg3, and
      protopanaxatriol-type ginsenosides) and untransformed ginsenosides Re, Rg1, and
      Rd were detected at 24 h. The results indicated that the primary metabolites are
      compound K and Rh1, and the protopanaxadiol-type ginsenosides were more easily
      metabolized than protopanaxatriol-type ginsenosides. CONCLUSION: This is the
      first report of the identification and quantification of the metabolism and
      metabolic profile of P. ginseng extract in rat intestinal microflora using LC
      MS/MS. The current study provided new insights for studying the metabolism and
      active metabolites of P. ginseng.

PMID- 29021703
TI  - Ginsenoside Rg3-enriched red ginseng extract inhibits platelet activation and in
      vivo thrombus formation.
AB  - BACKGROUND: Korean Red Ginseng has been used for several decades to treat many
      diseases, enhancing both immunity and physical strength. Previous studies have
      documented the therapeutic effects of ginseng, including its anticancer,
      antiaging, and anti-inflammatory activities. These activities are mediated by
      ginsenosides present in the ginseng plant. Ginsenoside Rg3, an effective compound
      from red ginseng, has been shown to have antiplatelet activity in addition to its
      anticancer and anti-inflammatory activities. Platelets are important for both
      primary hemostasis and the repair of the vessels after injury; however, they also
      play a crucial role in the development of acute coronary diseases. We prepared
      ginsenoside Rg3-enriched red ginseng extract (Rg3-RGE) to examine its role in
      platelet physiology. METHODS: To examine the effect of Rg3-RGE on platelet
      activation in vitro, platelet aggregation, granule secretion, intracellular
      calcium ([Ca2+]i) mobilization, flow cytometry, and immunoblot analysis were
      carried out using rat platelets. To examine the effect of Rg3-RGE on platelet
      activation in vivo, a collagen plus epinephrine-induced acute pulmonary
      thromboembolism mouse model was used. RESULTS: We found that Rg3-RGE
      significantly inhibited collagen-induced platelet aggregation and [Ca2+]i
      mobilization in a dose-dependent manner in addition to reducing ATP release from
      collagen-stimulated platelets. Furthermore, using immunoblot analysis, we found
      that Rg3-RGE markedly suppressed mitogen-activated protein kinase phosphorylation
      (i.e., extracellular stimuli-responsive kinase, Jun N-terminal kinase, p38) as
      well as the PI3K (phosphatidylinositol 3 kinase)/Akt pathway. Moreover, Rg3-RGE
      effectively reduced collagen plus epinephrine-induced mortality in mice.
      CONCLUSION: These data suggest that ginsenoside Rg3-RGE could be potentially be
      used as an antiplatelet therapeutic agent against platelet-mediated
      cardiovascular disorders.

PMID- 29021704
TI  - The effect of red ginseng and ginseng leaves on the substance and energy
      metabolism in hypothyroidism rats.
AB  - BACKGROUND: Recent studies have revealed that the properties Traditional Chinese
      Medicine is mostly associated with are substance and energy metabolism. Our study
      aimed to compare the effect of red ginseng (RG) (warm property) and ginseng
      leaves (GL; cold property) on the substance and energy metabolism of rats with
      hypothyroidism. MATERIALS AND METHODS: Rats were administered propylthiouracil
      intraperitoneally for 20 d to cause hypothyroidism. The reference group was
      orally administered Aconiti Lateralis Radix Praeparaia [FZ (Fuzi in Chinese)],
      while both the RG and GL groups were orally administrated crude drugs. The
      rectal, tail, toe, and axilla temperature of the rats were assayed every 3 d.
      Oxygen consumption, carbon dioxide production, heat production, and energy
      expenditure were measured via TSE phenoMaster/LabMaster animal monitoring system.
      Adenosine monophosphate-activated protein kinase, Na+-K+-ATPase, fumarase,
      pyruvic acid and cyclic adenosine monophosphate/cyclic guanosine monophosphate
      were determined. RESULTS: The lower levels of triiodothyronine,
      tetraiodothyronine, and thyrotropin-releasing hormone and the higher level of
      thyroid stimulating hormone revealed the successful establishment of a
      hypothyroidism model. Oxygen consumption, carbon dioxide production, heat
      production, and energy expenditure in the FZ and RG groups were obviously
      increased. The activity of Na+-K+-ATPase and fumarase in the FZ and RG groups was
      significantly increased. The cyclic adenosine monophosphate/cyclic guanosine
      monophosphate level in the FZ and RG groups was increased, while the GL group
      showed the opposite. CONCLUSION: Our research provides a new way to explore the
      efficiency of Chinese medicine on the basis of the relationship between drug
      property and effects on substance and energy metabolism.

PMID- 29021705
TI  - Global analysis of ginsenoside Rg1 protective effects in beta-amyloid-treated
      neuronal cells.
AB  - BACKGROUND: A number of reports have described the protective effects of
      ginsenoside Rg1 (Rg1) in Alzheimer's disease (AD). However, the protective
      mechanisms of Rg1 in AD remain elusive. METHODS: To investigate the potential
      mechanisms of Rg1 in beta-amyloid peptide-treated SH-SY5Y cells, a comparative
      proteomic analysis was performed using stable isotope labeling with amino acids
      in cell culture combined with nano-LC-MS/MS. RESULTS: We identified a total of
      1,149 proteins in three independent experiments. Forty-nine proteins were
      significantly altered by Rg1 after exposure of the cells to beta-amyloid
      peptides. The protein interaction network analysis showed that these altered
      proteins were clustered in ribosomal proteins, mitochondria, the actin
      cytoskeleton, and splicing proteins. Among these proteins, mitochondrial proteins
      containing HSD17B10, AARS2, TOMM40, VDAC1, COX5A, and NDUFA4 were associated with
      mitochondrial dysfunction in the pathogenesis of AD. CONCLUSION: Our results
      suggest that mitochondrial proteins may be related to the protective mechanisms
      of Rg1 in AD.

PMID- 29021706
TI  - Effect of hydrothermal processing on ginseng extract.
AB  - BACKGROUND: Panax ginseng Meyer is cultivated because of its medicinal effects on
      the immune system, blood pressure, and cancer. Major ginsenosides in fresh
      ginseng are converted to minor ginsenosides by structural changes such as
      hydrolysis and dehydration. The transformed ginsenosides are generally more
      bioavailable and bioactive than the primary ginsenosides. Therefore, in this
      study, hydrothermal processing was applied to ginseng preparation to increase the
      yields of the transformed ginsenosides, such as 20(S)-Rg3, Rk1, and Rg5, and
      enhance antioxidant activities in an effective way. METHODS: Ginseng extract was
      hydrothermally processed using batch reactors at 100-160 degrees C with differing
      reaction times. Quantitative analysis of the ginsenoside yields was performed
      using HPLC, and the antioxidant activity was qualitatively analyzed by evaluating
      2,2'-azino-bis radical cation scavenging, 2,2-diphenyl-1-picrylhydrazyl radical
      scavenging, and phenolic antioxidants. Red ginseng and sun ginseng were prepared
      by conventional steaming as the control group. RESULTS: Unlike steaming, the
      hydrothermal process was performed under homogeneous conditions. Chemical
      reaction, heat transfer, and mass transfer are generally more efficient in
      homogeneous reactions. Therefore, maximum yields for the hydrothermal process
      were 2.5-25 times higher than those for steaming, and the antioxidant activities
      showed 1.6-4-fold increases for the hydrothermal process. Moreover, the reaction
      time was decreased from 3 h to 15-35 min using hydrothermal processing.
      CONCLUSION: Therefore, hydrothermal processing offers significant improvements
      over the conventional steaming process. In particular, at temperatures over 140
      degrees C, high yields of the transformed ginsenosides and increased antioxidant
      activities were obtained in tens of minutes.

PMID- 29021707
TI  - Pectinase-treated Panax ginseng protects against chronic intermittent heat stress
      induced testicular damage by modulating hormonal and spermatogenesis-related
      molecular expression in rats.
AB  - BACKGROUND: Elevated testicular temperature disrupts spermatogenesis and causes
      infertility. In the present study, the protective effect of enzymatically
      biotransformed Panax ginseng Meyer by pectinase (GINST) against chronic
      intermittent heat stress-induced testicular damage in rats was investigated.
      METHODS: Male Sprague-Dawley rats (4 wk old, 60-70 g) were divided into four
      groups: normal control (NC), heat-stress control (HC), heat-stress plus GINST-100
      mg/kg (HG100), and heat-stress plus GINST-200 mg/kg (HG200) treatment groups.
      Each dose of GINST (100 mg/kg and 200 mg/kg) was mixed separately with a regular
      pellet diet and was administered orally for 24 wk. For inducing heat stress, rats
      in the NC group were maintained at 25 degrees C, whereas rats in the HC, HG100,
      and HG200 groups were exposed to 32 +/- 1 degrees C for 2 h daily for 6 mo. At
      week 25, the testes and serum from each animal were analyzed for various
      parameters. RESULTS: Significant (p < 0.01) changes in the sperm kinematic values
      and blood chemistry panels were observed in the HC group. Furthermore,
      spermatogenesis-related molecules, sex hormone receptors, and selected
      antioxidant enzyme expression levels were also altered in the HC group compared
      to those in the NC group. GINST (HS100 and HS200) administration significantly (p
      < 0.05) restored these changes when compared with the HC group. For most of the
      parameters tested, the HG200 group exhibited potent effects compared with those
      exhibited by the HG100 group. CONCLUSION: GINST may be categorized as an
      important medicinal herb and a potential therapeutic for the treatment of male
      subfertility or infertility caused by hyperthermia.

PMID- 29021709
TI  - Subacute oral toxicity and bacterial mutagenicity study of Korean Red Ginseng
      oil.
AB  - BACKGROUND: Red ginseng oil (RGO) is produced by supercritical CO2 extraction of
      secondary products derived from Korean Red Ginseng extract. As the use of RGO has
      increased, product safety concerns have become more important. METHODS: In the
      present study, the subacute oral toxicity and bacterial reverse mutagenicity of
      RGO were evaluated. Sprague-Dawley rats were orally administered with RGO for 28
      d by gavage. Daily RGO dose concentrations were 0 mg/kg body weight (bw), 500
      mg/kg bw, 1,000 mg/kg bw, or 2,000 mg/kg bw per day. Bacterial reverse mutation
      tests included five bacterial strains (Escherichia coli WP2 and Salmonella
      typhimurium TA98, TA100, TA1535, and TA1537), which were used in the presence or
      absence of metabolic activation. The plated incorporation method for mutation
      test was used with RGO concentrations ranging from 312.5 MUg to 5,000 MUg per
      plate. RESULTS: The subacute oral toxicity test results did not reveal any marked
      changes in clinical characteristics. There were no toxicological changes related
      to RGO administration in hematological and serum biochemical characteristics in
      either control or treatment animals. Furthermore, no gross or histopathological
      changes related to RGO treatment were observed. The bacterial reverse mutation
      test results did not reveal, at any RGO concentration level and in all bacterial
      strains, any increase in the number of revertant colonies in the RGO treatment
      group compared to that in the negative control group. CONCLUSION: The no-observed
      adverse-effect level of RGO is greater than 2,000 mg/kg bw and RGO did not induce
      genotoxicity related to bacterial reverse mutations.

PMID- 29021708
TI  - Effects of ginseng on stress-related depression, anxiety, and the hypothalamic
      pituitary-adrenal axis.
AB  - Ginseng effectively regulates the immune response and the hormonal changes due to
      stress, thus maintaining homeostasis. In addition to suppressing the occurrence
      of psychological diseases such as anxiety and depression, ginseng also prevents
      stress-associated physiological diseases. Recent findings have revealed that
      ginseng is involved in adjusting the hypothalamic-pituitary-adrenal axis and
      controlling hormones, thus producing beneficial effects on the heart and brain,
      and in cases of bone diseases, as well as alleviating erectile dysfunction.
      Recent studies have highlighted the potential use of ginseng in the prevention
      and treatment of chronic inflammatory diseases such as diabetes, rheumatoid
      arthritis, and allergic asthma. However, the mechanism underlying the effects of
      ginseng on these stress-related diseases has not been completely established. In
      this review, we focus on the disease pathways caused by stress in order to
      determine how ginseng acts to improve health. Central to our discussion is how
      this effective and stable therapeutic agent alleviates the anxiety and depression
      caused by stress and ameliorates inflammatory diseases.

PMID- 29021710
TI  - Melanogenesis inhibition activity of floralginsenoside A from Panax ginseng
      berry.
AB  - BACKGROUND: Panax ginseng is a traditional herb used for medicinal purposes in
      eastern Asia. P. ginseng contains various ginsenosides with pharmacological
      effects. In this study, floralginsenoside A (FGA), ginsenoside Rd (GRD), and
      ginsenoside Re (GRE) were purified from P. ginseng berry. METHODS: Chemical
      structures of FGA, GRD, and GRE were determined based on spectroscopic methods,
      including fast atom bombardment mass spectroscopy, ID-nuclear magnetic resonance,
      and infrared spectroscopy. Inhibitory activities of these compounds on
      melanogenesis were studied by measuring the expression of protein and melanin
      content in the melan-a cell line. This inhibitory activity was confirmed by
      observing pigmentation and tyrosinase activities of zebrafish. RESULTS: GRD, GRE,
      and FGA were not cytotoxic at concentrations less than 20MUM, 80MUM, and 160MUM
      in melan-a cells, respectively. GRD, GRE, and FGA inhibited melanin biosynthesis
      in melan-a cells by 15.2%, 22.9%, and 23.9% at 20MUM, 80MUM, and 160MUM,
      respectively. FGA was observed to display the most potent inhibitory effect. In
      addition, FGA decreased microphthalmia-associated transcription factor protein
      expression in a dose-dependent manner. Moreover, FGA induced extracellular signal
      regulated kinase phosphorylation level in melan-a cells. In addition, melanin
      pigment content and tyrosinase activity in zebrafish treated with FGA at160MUM
      were reduced. CONCLUSION: FGA showed the most potent inhibition of melanogenesis
      in both in vitro and in vivo studies. This study suggests that FGA purified from
      P. ginseng may be an effective melanogenesis inhibitor.

PMID- 29021711
TI  - Ginsenoside Rg1 from Panax ginseng enhances myoblast differentiation and myotube
      growth.
AB  - BACKGROUND: Ginsenoside Rg1 belongs to protopanaxatriol-type ginsenosides and has
      diverse pharmacological activities. In this report, we investigated whether Rg1
      could upregulate muscular stem cell differentiation and muscle growth. METHODS:
      C2C12 myoblasts, MyoD-transfected 10T1/2 embryonic fibroblasts, and HEK293T cells
      were treated with Rg1 and differentiated for 2 d, subjected to immunoblotting,
      immunocytochemistry, or immunoprecipitation. RESULTS: Rg1 activated promyogenic
      kinases, p38MAPK (mitogen-activated protein kinase) and Akt signaling, that in
      turn promote the heterodimerization with MyoD and E proteins, resulting in
      enhancing myogenic differentiation. Through the activation of Akt/mammalian
      target of rapamycin pathway, Rg1 induced myotube growth and prevented
      dexamethasone-induced myotube atrophy. Furthermore, Rg1 increased MyoD-dependent
      myogenic conversion of fibroblast. CONCLUSION: Rg1 upregulates promyogenic
      kinases, especially Akt, resulting in improvement of myoblast differentiation and
      myotube growth.

PMID- 29021712
TI  - Chronic dietary ginseng extract administration ameliorates antioxidant and
      cholinergic systems in the brains of aged mice.
AB  - BACKGROUND: Black ginseng has a more potent biological activity than non-steamed
      ginseng. We investigated the effects of long-term intake of dietary black ginseng
      extract (BG) on antioxidant activity in aged mice. We also compared the effects
      of BG on cognitive deficits with those of white ginseng extract (WG) and red
      ginseng extract (RG). METHODS: Ten-month-old mice were fed an AIN-93G-based diet
      containing 10 g/kg (low dose, L) or 30 g/kg (high dose, H) WG powder, RG powder,
      or BG powder for 24 wk. We measured serum lipids, the activities of antioxidant
      enzymes, and malondialdehyde levels. Additionally, the protein expression levels
      of choline acetyltransferase and vesicular acetylcholine transporter, which are
      presynaptic cholinergic markers in the cortex and hippocampus of the brain, were
      measured by western blotting. RESULTS: Triglyceride levels were reduced in all
      the extract-treated mice, except those in the LBG group. High-density lipoprotein
      cholesterol levels in the HBG group were higher than those in the control group.
      Total cholesterol levels were reduced in the LBG group. Additionally, glucose
      levels in the HBG group were significantly reduced by 41.2%. There were lower
      levels of malondialdehyde in the LBG group than in the control group.
      Furthermore, glutathione reductase activity increased in the HWG group and the
      HRG group. The protein expression levels of choline acetyltransferase and
      vesicular acetylcholine transporter significantly increased in all the ginseng
      treated groups. CONCLUSION: The results suggest that supplementation with the
      tested ginseng extracts may suppress the cognitive decline associated with aging,
      via regulation of the cholinergic and antioxidant defense systems.

PMID- 29021713
TI  - Epidemiology of bronchiolitis: a description of emergency department visits and
      hospitalizations in Puerto Rico, 2010-2014.
AB  - BACKGROUND: Little is known about the epidemiology of bronchiolitis as a clinical
      diagnosis and its impact on emergency department visits and hospitalizations in
      tropical and semitropical regions. We described the epidemiology of bronchiolitis
      emergency visits and hospitalizations, its temporal trend and geographic
      distribution in Puerto Rico between 2010 and 2014. METHODS: We performed a
      retrospective descriptive analysis of a representative sample of privately
      insured children with bronchiolitis from January 2010 to December 2014. Data was
      provided by the largest private health insurer in Puerto Rico and identified
      children < 24 months of age with bronchiolitis by International Classification of
      Diseases, Ninth Revision code 466, 466.11, and 466.19. Chi-square and one-way
      ANOVA compared sex, age, diagnosis, and severity across the years. Joinpoint
      Poisson regression analysis evaluated the temporal trend distribution of
      bronchiolitis hospitalizations per calendar year. A P value less than 0.05 was
      statistically significant. RESULTS: During the study period, the annual
      proportion of emergency department visits and hospitalizations due to
      bronchiolitis increased from 3 to 5%, and 26 to 38%, respectively. The annual
      incidence rate of hospitalizations was 3.2 per 1000 privately insured children <
      24 months. Non-RSV bronchiolitis was the most frequent diagnosis (51%).
      Hospitalizations occurred year-round, but increased significantly from August
      through December. Most children hospitalized resided in the metropolitan San Juan
      (35%) and surrounding urban areas. Total hospital charges decreased from $3.78 to
      $3.74 million, with an average cost per hospitalization of $4320.12 (11.3%
      increase; P = 0.0015). CONCLUSIONS: This is the first study that evaluates the
      epidemiological characteristics of bronchiolitis in a primarily Hispanic
      population, living in a tropical country, and using data from a privately insured
      population. We found a small but significant increase in proportion of emergency
      visits and hospitalizations. Temporal trend shows year-round hospitalizations
      with an earlier seasonal peak and longer duration, consistent with Puerto Rico's
      seasonal rainfall throughout the study period. Further studies are needed to
      elucidate whether this epidemiologic pattern can also be seen in publicly insured
      children and whether Hispanic ethnicity is a risk factor for increased
      hospitalizations or is related to health disparities in the US healthcare system.

PMID- 29021714
TI  - Enhancing utility and understanding of evidence based practice through
      undergraduate nurse education.
AB  - BACKGROUND: The concept of evidence-based practice is globally relevant in
      current healthcare climates. However, students and teachers struggle with
      integrating evidence based practice effectively into a curriculum. This has
      implications for nurse education and in particular the way in which research is
      presented and delivered to students. A new undergraduate Evidence Based Practice
      module (Evidence Based Nursing 1) was developed in a large University within the
      United Kingdom. It commenced in October 2014 running in year one of a 3 year
      undergraduate nursing programme. This study sought to formally evaluate attitudes
      and beliefs, knowledge level and utilization of evidence based practice though
      using two validated questionnaires: Evidence Based Practice Beliefs Scale(c) and
      Evidence Based Practice Implementation Scale(c). METHOD: This was a pilot study
      using quantitative pre and post-test design. Anonymised data was collected from
      Year 1 undergraduate student nurses in the September 2014 intake (n = 311) at two
      time points. Time 1: pre-module in September 2014; and Time 2: post -module in
      August 2015. All data was collected via Survey Monkey. RESULTS: Results
      demonstrate that the educational initiative positively impacted on both the
      beliefs and implementation of evidence based practice. Analysis highlighted
      statistically significant changes (p < 0.05) in both the Evidence Based Practice
      Beliefs Scale (7/16 categories) and the Evidence Based Practice Implementation
      Scale (13 / 18 categories). CONCLUSIONS: The significance of integrating evidence
      based practice into undergraduate nurse education curriculum cannot be
      underestimated if evidence based practice and its positive impact of patient care
      are to be appreciated in healthcare settings internationally.

PMID- 29021715
TI  - The clinicopathological significance of UBE2C in breast cancer: a study based on
      immunohistochemistry, microarray and RNA-sequencing data.
AB  - BACKGROUND: Ubiquitin-conjugating enzyme E2C (UBE2C) has been previously reported
      to correlate with the malignant progression of various human cancers, however,
      the exact molecular function of UBE2C in breast carcinoma (BRCA) remained
      elusive. We aimed to investigate UBE2C expression in BRCA and its clinical
      significance. METHODS: The expression of UBE2C in 209 BRCA tissue samples and 53
      adjacent normal tissue samples was detected using immunohistochemistry. The
      clinical role of UBE2C was analyzed. Public databases including the human protein
      atlas and Oncomine were used to assess UBE2C expression in BRCA. Moreover, the
      cancer genome atlas (TCGA) database was employed to investigate the prognostic
      value of UBE2C in BRCA. RESULTS: The positive expression rate of UBE2C in BRCA
      was 70.8% (148/209), and UBE2C expression in the adjacent breast tissue was
      negative. The expression of UBE2C was positively correlated with tumor size (r =
      0.32, P < 0.001), histological grade (r = 0.237, P = 0.001), clinical stage (r =
      0.198, P = 0.004), lymph node metastasis (r = 0.155, P = 0.026), HER2 expression
      level (r = 0.356, P < 0.001), Ki-67 expression level (r = 0.504, P < 0.001), and
      P53 expression level (r = 0.32, P = 0.001). Negative correlations were found
      between UBE2C expression and the ER (r = - 0.403, P < 0.001) and PR (r = - 0.468,
      P < 0.001) status. UBE2C gene expression data from the public databases all
      proved that UBE2C was overexpressed in BRCA. According to the TCGA data analysis,
      a higher positive expression of UBE2C was associated with worse survival of BRCA
      patients (P = 0.0428), and data from cBioPortal indicated that 11% of all
      sequenced BRCA patients possessed a gene alteration of UBE2C, predominately gene
      amplification and mRNA regulation. CONCLUSION: Ubiquitin-conjugating enzyme E2C
      might pose an oncogenic effect on the progression of BRCA.

PMID- 29021716
TI  - Continuous Curvilinear Capsulorhexis Training and Non-Rhexis Related Vitreous
      Loss: The Specificity of Virtual Reality Simulator Surgical Training (An American
      Ophthalmological Society Thesis).
AB  - PURPOSE: To assess the specificity of simulation-based virtual reality ophthalmic
      cataract surgery training on the Eyesi ophthalmic virtual reality surgical
      simulator, and test the hypothesis that microsurgical motor learning is highly
      specific. METHODS: Retrospective educational interventional case series. The
      rates of vitreous loss and retained lens material, and vitreous loss and retained
      lens material associated with an errant continuous curvilinear capsulorhexis
      (CCC) were assessed among 1037 consecutive cataract surgeries performed during
      four consecutive academic years at a teaching hospital. The data were grouped by
      Eyesi use and capsulorhexis intensive training curriculum (CITC) completion. The
      main intervention was the completion of the CITC on the Eyesi. RESULTS: In the
      Eyesi simulator experience-based stratification, the vitreous loss rate was
      similar in each group (chi square p=0.95) and was not preceded by an errant CCC
      in 86.2% for "CITC done at least once", 57.1% for "CITC not done, but some Eyesi
      use", and 48.9% for "none" training groups (p=4*10-5). Retained lens material
      overall and occurring among the errant CCC cases was similar among training
      groups (p=0.82 and p=0.71, respectively). CONCLUSIONS: Eyesi capsulorhexis
      training was not associated with lower vitreous loss rates overall. However, non
      errant CCC associated vitreous loss was higher among those who underwent Eyesi
      capsulorhexis training. Training focused on the CCC portion of cataract surgery
      may not reduce vitreous loss unassociated with an errant CCC. It is likely that
      surgical training is highly specific to the task being trained. Residents may
      need to be trained for all surgical steps with adequate intensity to minimize
      overall complication rates.

PMID- 29021719
TI  - ?
AB  - The frequency of work-related electrical injuries has dropped but their
      characteristics remain unknown in our country. This survey aimed to describe the
      work-related electrical injuries that occurred in Yaounde during the period 2005
      2014. The study was carried out in Yaounde-based central level hospitals from
      February 1st, 2015 to May 10th, 2015. Data from the files of the victims of these
      accidents were collated and analyzed. Socio-demographic, professional and
      epidemiological data were described and results were presented in descriptive
      mode. The sample comprised 25 males (83.3%) and 5 females (16.7%). The mean age
      was 28+/-8.3 years. Three out of four victims were working in the informal
      sector. Accidents were caused by low voltage current (56.7%). The victims were
      usually electricians and electrical workers (24%). Accidents occurred at various
      locations, such as in workshops and in the yard and at different times of the
      day. We recommend that specific training sessions targeting these workers of the
      informal sector be organized in order to prevent these dangerous accidents.

PMID- 29021718
TI  - Epidemiology and outcome of 2,590 burned patients in Northwest Iran.
AB  - Burns are calamities with considerable morbidity and mortality rates. We
      attempted to examine the epidemiology of burns in Zanjan city, in northwest Iran,
      by a systematic study of existing information. The medical files of 2,590 thermal
      burn patients treated in our hospital in Zanjan city, Iran, from December 2010 to
      November 2016 were studied. Patient information, including age, sex, burn degree,
      season, cause of burn, hospital stay and treatment results were analyzed. About
      65% of the patients were male (n=1691). Most burns (92.8%) were less than 30%
      total body surface area. Mean age and hospital stay were 25.4 years old and 9.1
      days, respectively. The most common causes of burn were hot liquids, gas
      explosion and fire, respectively. Except for self-immolation, which was more
      common among men, there was no significant relationship between cause of burn and
      the studied variables. The six-year mortality rate was 2.9%, and was more common
      in the years 2011 to 2013. In addition, distribution of causes of burn had a
      significant trend (variation). Fire burn had a decreasing trend and gas and
      chemical burn had increasing trends in this period. In northwest Iran the causes
      of burn changed over the six years. Chemical burns, gas explosion burns and burn
      mortality increased. Some of these results were due to economic and
      pharmaceutical sanctions in Iran. Because of Iran's industrial development, it is
      recommended that preventive measures for chemical, gas and electrical burns be
      conducted.

PMID- 29021717
TI  - Enhanced Detection of Sub-Retinal Pigment Epithelial Cell Layer Deposits in Human
      and Murine Tissue: Imaging Zinc as a Biomarker for Age-Related Macular
      Degeneration (An American Ophthalmological Society Thesis).
AB  - PURPOSE: Understanding the apparent paradoxical role of zinc in the pathogenesis
      and prevention of age-related macular degeneration (AMD) has been limited by the
      lack of animal models for its detection in sub-retinal epithelial deposits
      (drusen), a definitive early hallmark of AMD. In-vitro studies using Zinpyr-1
      showed drusen contained high levels of zinc, but the probe was not suitable for
      in-vivo studies. This study compares Zinpyr-1 to ZPP1, a new fluorescein-based
      probe for zinc, to assess the potential of ZPP1 for in-vivo detection of zinc in
      drusen. METHODS: Flat mounts of human sub-RPE tissue using the probes were
      analyzed by fluorescence and confocal microscopy. Flat mounts of sub-RPE tissue
      from mice deficient in superoxide dismutase isoform-1 (CuZn-SOD-KO) or isoform-2
      (Mn-SOD-RPE-KO) were analyzed with sub-RPE deposits confirmed by histology.
      RESULTS: Drusen are detected in greater numbers and intensity with ZPP1 compared
      to Zinpyr-1. Using ZPP1, drusen was detected in a sample from a 46-year old human
      donor without ocular history, suggesting that ZPP1 might be sensitive enough to
      detect drusen at an early stage. With CuZn-SOD KO mice, ZPP1 detected sub-RPE
      deposits at 10 months of age, whereas Zinpyr-1 required 14 months. CONCLUSION:
      Detection of sub-RPE deposits by ZPP1 was greatly enhanced compared to Zinpyr-1.
      This enhanced sensitivity will allow for more insightful analysis of zinc in AMD
      using human specimens and mouse models. This could result in the development of a
      sensitive in-vivo probe to enhance research on the role zinc in drusen formation
      and the early clinical diagnosis of AMD.

PMID- 29021721
TI  - The effect of comorbidities and complications on the mortality of burned
      patients.
AB  - The World Health Organization has defined 'elderly' as 65 years or older. Age is
      a known major prognostic factor after burn injury. The objective of this study is
      to establish whether epidemiologic differences in the elderly contribute to
      higher mortality compared to younger patients. Patients admitted to the burn unit
      between 2011 and 2014 (229 patients) were included: 159 were under 65 years old
      and 70 (30.6%) were 65 or over. The elderly group had a higher mortality rate,
      24.6% versus 8.2% (p=0.002). Patients over 65 presented more pre-existing co
      morbidities (1.7 +/- 1.1) than patients under 65 (1.1 +/- 1.0), p<0.001, and COPD
      was significantly associated with higher mortality rate (p=0.014). Patients over
      and under 65 suffered similar TBSA, 15.7 versus 14.1, p=0.720. Regarding burn
      depth, deeper burns were significantly more prevalent in the over 65 group (17.1%
      vs. 5.0%, p=0.003). Patients over 65 developed more complications (0.9 +/- 1.1)
      than the under 65s (0.5 +/- 0.9), p=0.009, and sepsis was significantly
      associated with higher mortality rate (p=0.042). Over-65-year-old burn victims
      have a higher mortality risk than the under 65s. Elderly patients generally have
      more pre-existing comorbidities and develop more complications during hospital
      stay, which increase the mortality risk. Apparently, history of COPD or sepsis
      complication during hospital stay are independent risk factors for death in the
      elderly group. Although over-65-year-olds presented similar TBSA to the younger
      patients, the proportion of deep burns was higher, which suggests that burns
      might be more aggressive in the elderly.

PMID- 29021722
TI  - Bacterial and antimicrobial susceptibility profile and the prevalence of sepsis
      among burn patients at the burn unit of Cipto Mangunkusumo Hospital.
AB  - Infection is a major cause of mortality and morbidity among burn patients. An
      effective measure to reduce infection is routine monitoring of bacterial
      infection and antimicrobial susceptibility patterns at the burn unit. This will
      help to create a burn centre-specific empirical antibiotic therapy protocol. A
      retrospective, descriptive study was conducted at the Cipto Mangunkusumo Hospital
      (RSCM) Burn Unit between September-November 2016. Data regarding bacterial
      culture isolates, antimicrobial susceptibility spectrum, and the number of burn
      patients diagnosed with sepsis were collected. There were 36 patients with
      positive bacterial cultures, with the isolates changing continuously between
      Klebsiella pneumonia (17%), Pseudomonas Aeruginosa (12%) and Acinetobacter
      baumannii (11%). High resistance was found for 10 antimicrobials, particularly
      cephalosporins. The three bacteria were only sensitive to carbapenem,
      aminoglycosides and tigecycline. Fourteen patients were diagnosed with sepsis
      (38.9%), 10 died. Two major sepsis-causing bacteria were P. aeruginosa (33.3%)
      and K. pneumoniae (28.9%). Bacterial isolates in our setting changed every month.
      Almost all bacterial isolates are multi-drug resistant, highly resistant to the
      empirical therapy given (ceftriaxone), leading to outbreaks of sepsis and
      increased mortality rates. Carbapenem (imipenem, meropenem and doripenem) and
      aminoglycosides (amikacin) combination was the selected empirical therapy.

PMID- 29021720
TI  - Burn injury: review of pathophysiology and therapeutic modalities in major burns.
AB  - Despite a considerable decrease in their incidence worldwide, burn injuries
      remain one of the commonest forms of trauma and account for a weighty proportion
      of trauma cases in health-care emergencies around the globe. Although the latest
      data reveal a substantial decline in burn-related mortality and hospital
      admissions in the US over the past three decades, severe thermal injuries
      continue to trigger devastating morbidity and significant mortality while their
      management remains a dynamic challenge for the entire medical and paramedical
      community. Concrete evidence continues to be established regarding burn
      associated pathophysiologic responses, and their destructive sequelae and
      deleterious effects in survivors at cellular, systemic as well as socio-economic
      level. Better understanding of these responses have contributed to advances in
      therapeutic strategies, improved long-term outcomes and catalyzed the
      reintegration of victims back into society. This paper describes the current
      understanding of the pathophysiology of a burn injury and characterizes both
      local and systemic pathophysiologic responses in terms of metabolic,
      hemodynamics, cardiac, renal, hepatic, gastro-intestinal, immunologic, endocrine
      as well as male reproductive systems in an attempt to understand the
      corresponding treatment modalities for this unique patient population.

PMID- 29021723
TI  - Bacterial infections in burn wound patients at a tertiary teaching hospital in
      Accra, Ghana.
AB  - Intact human skin surface is essential for protection against infection,
      preservation of body fluid homeostasis and thermoregulation. Burn injury
      compromises the skin barrier and enables bacterial infection, hence delaying burn
      wound healing. This study aimed to determine the microbial profile of burn
      wounds, and resistance patterns of microbes with respect to the source of the
      injured patient's wound. Fifty wound swab samples were collected from fifty burn
      patients at the Korle-Bu Teaching Hospital, Accra (KBTH). Sterile swabs moistened
      with sterile saline were used to swab burn wounds. The swabs were plated on blood
      agar and MacConkey agar for 24 hrs at 37 degrees C. Biochemical tests were
      carried out on the representative isolate on each plate, and antibacterial
      sensitivity pattern was determined using the Kirby-Bauer disc diffusion method.
      The study revealed that the main source of burns was gas flames (66%) and scalds
      (28%). Out of the 50 samples analysed, 86% were culture positive and 14% were
      culture negative for bacteria. The predominant organisms isolated were
      Pseudomonas sp. (30.2%) and Acinetobacter sp. (20.9%). Proteus mirabillis (2.3%)
      and Staphylococcus aureus (2.3%) were the least frequently isolated bacteria.
      Although Pseudomonas sp. showed varying resistance levels to gentamicin,
      cotrimoxazole and ciprofloxacin, all the Acinetobacter sp. were resistant to most
      of the tested antibiotics used. Resistant gram negative bacteria are the most
      common isolates associated with burn wounds in Accra, Ghana. Hence a careful
      selection of antibiotics to control the wound infection is required for proper
      management of burn wounds in order to help reduce morbidity and mortality.

PMID- 29021724
TI  - Inhalation injury in a burn unit: a retrospective review of prognostic factors.
AB  - Inhalation injury (InI) is known to seriously affect the prognosis of burn
      patients, as it is strongly associated with high morbidity and mortality. Despite
      major advances in the treatment of burn patients in the past years, advances in
      the treatment of smoke InI have been somewhat limited; mortality reduction mostly
      results from improvements in critical care. It is difficult to separate the
      contribution of InI from other mechanisms that also affect respiratory tract and
      lungs. The aim of this study was to compare patients with and without InI and to
      identify prognostic factors among patients with smoke InI. Patients with InI
      displayed higher total body surface area (TBSA) burned, higher incidence of
      pneumonia and acute respiratory distress syndrome (ARDS), a higher rate of
      positive blood cultures and a significantly higher death rate. We could conclude
      that older age, higher TBSA, ARDS and pneumonia were independent predictive
      factors for mortality in our global study population. Older age and higher TBSA
      were the only independent factors found to be predictive of mortality in patients
      with InI.

PMID- 29021725
TI  - Prehospital hydroxocobalamin for inhalation injury and cyanide toxicity in the
      United States - analysis of a database and survey of ems providers.
AB  - Prehospital use of hydroxocobalamin as an antidote for cyanide toxicity, a
      serious complication of smoke inhalation, has yet to be universally adopted in
      the United States though its efficacy and safety have been demonstrated since
      2006. The purpose of this study was to characterize practices of prehospital
      hydroxocobalamin administration via a survey of emergency medical services (EMS)
      and to report a case series from an EMS database to track use of
      hydroxocobalamin. The Fire Smoke Coalition Newsletter emailed a voluntary survey
      to EMS subscribers regarding hydroxocobalamin use. Survey responses were analyzed
      in addition to survival data from the Smoke Inhalation Treatment Database (SITD),
      a publically available, self-reported, online database for EMS regarding smoke
      inhalation patient outcomes. Analysis was compared to current published data from
      PubMed. The survey had a 14% response rate (284/2000). Only 38% reported
      prehospital utilization of a hydrogen cyanide antidote with 46% using
      hydroxocobalamin. 20% of responders reported a formal ALS protocol was in place
      for hydroxocobalamin use. For the SITD, 12 of 13 (92%) patients who received
      hydroxocobalamin for suspected inhalation survived. Other studies found a
      survival rate of 72% and 42% after administration of hydroxocobalamin for smoke
      inhalation. Prehospital administration of hydroxocobalamin for cyanide toxicity
      is uncommon in the United States, as evidenced by this analysis, despite well
      documented safety and efficacy. Although a small sample, patients who received
      prehospital hydroxocobalamin had improved survival. This survival rate is
      significantly greater than those reported previously.

PMID- 29021726
TI  - Investigating the relationship between microalbuminuria and prognosis of patients
      with severe burns in the Motahari Burn Hospital.
AB  - Microalbuminuria seems to be a reflection of increased vascular permeability
      caused by systemic inflammatory response, and is likely to be a predictor of
      mortality, sepsis and other outcomes of severe burn patients. We investigated the
      impact of microalbuminuria on the prognosis of patients with severe burns. This
      is a prospective study on severe burn patients (above 20%) admitted in the first
      24 hours after burns to the Motahari Burn Hospital. Patients' microalbuminuria
      was measured at admission and 48 hours later, and its relationship with patient
      prognosis (sepsis, renal failure, death, inhalation injury and systemic
      inflammatory response syndrome) was analyzed. We concluded that microalbuminuria
      at admission in patients with severe burns was directly related to inhalation
      injury (P = 0.018), ARDS during hospitalization (P = 0.001) and length of
      hospital stay (P = 0.025). Moreover, microalbuminuria at 48 hours after admission
      had a direct connection with patient death (P = 0.001), sepsis (P = 0.001), renal
      failure (P = 0.001) and SIRS (P = 0.001). Microalbuminuria is a simple,
      noninvasive, fast and affordable test to predict sepsis, mortality, renal
      failure, systemic inflammatory response and a finding associated with inhalation
      injury in severe burn patients, making it a fast prognostic predictor that helps
      to improve the management of these patients.

PMID- 29021728
TI  - Olympic torch flap: one-stop option for simultaneous brow, upper and lower lid
      reconstruction in post burn patients.
AB  - Facial units reconstruction in a post burn patient poses tough challenges.
      Simultaneous brow and lid reconstruction is one of them. This article presents a
      45-year-old epileptic male with burn of complete face. The task of reconstructing
      the brow, upper and lower lids was successfully accomplished using a modification
      of the Guyuron postauricular fasciocutaneous flap, after initial grafting and
      radial forearm flap reconstruction of forehead and other parts of the face. The
      article gives a single-stop solution for simultaneous reconstruction of brow and
      lids using a random pattern extension of the traditional postauricular flap, thus
      proving the excellent vascularity and hence durability of the flap in spite of a
      180 degrees change in the orientation of the flap with respect to the axis.

PMID- 29021727
TI  - Analgesia, sedation and arousal status in burn patients: the gap between
      recommendations and current practices.
AB  - Assessment and treatment of pain, agitation and delirium are integral parts of
      the management of critically ill patients. The purpose of this review is to
      describe how pain, delirium and agitation are managed in general intensive care
      units and in burn units, and to address whether management of these issues is
      compatible with internationally accepted recommendations. A substantial gap
      exists between the conception of the guidelines, clinical practice and
      physicians' statements regarding pain, sedation and delirium management. Specific
      training programs might be required to increase the implementation rate of
      guidelines and best practices on sedation, pain and delirium assessment and
      management in burn units.

PMID- 29021729
TI  - Management of split skin graft donor site in the West African sub region: survey
      of plastic surgeons' practice.
AB  - Split skin graft (SSG) is one of the most commonly performed operations on any
      Plastic Surgery service. Rate of donor site healing is affected by various
      factors including the type of dressing applied. The aim of this study was to
      survey the practice of plastic surgeons in the sub region with respect to
      management of SSG donor site and see how it conforms to international standards.
      Structured questionnaires on various aspects of the harvest and management of SSG
      donor sites were administered to plastic surgeons during the 53rd annual
      conference of the West African College of Surgeons (WACS) at Lome, Togo in March
      2013. The data were analyzed using descriptive statistics. There were 47
      respondents out of 55 plastic surgeons from four West African countries, which
      represented 85.4% of registered participants at the plastic surgery section of
      the conference. All the respondents performed SSG regularly, and the thigh was
      the most commonly used donor site. Different types of paraffin gauze remained the
      most commonly used primary donor site dressing. Only 17% of the respondents apply
      a topical local anaesthetic agent on the donor site. The choice of SSG donor site
      dressing in the sub region was driven mainly by availability. Concerted efforts
      must be made to access newer wound care products for optimum management of this
      commonly performed operation.

PMID- 29021731
TI  - MBC News.

PMID- 29021730
TI  - Case report of a high voltage electrical injury and review of the indications for
      early fasciotomy in limb salvage of an electrically injured limb.
AB  - Electrical injuries make up a relatively small portion of burn injuries. Safety
      measures in place on domestic electricity supply have reduced the occurrence of
      high voltage electrical injuries. We present the case of a young man who
      sustained a high voltage electrical injury on all four limbs. Early fasciotomy
      was performed on both his hands and forearms. Despite early compartment release,
      the left upper limb deteriorated and required amputation. In this article we
      discuss the indications, outcomes and complications of early fasciotomy.

PMID- 29021732
TI  - Nanoparticle size distribution quantification: results of a small-angle X-ray
      scattering inter-laboratory comparison.
AB  - This paper presents the first worldwide inter-laboratory comparison of small
      angle X-ray scattering (SAXS) for nanoparticle sizing. The measurands in this
      comparison are the mean particle radius, the width of the size distribution and
      the particle concentration. The investigated sample consists of dispersed silver
      nanoparticles, surrounded by a stabilizing polymeric shell of poly(acrylic acid).
      The silver cores dominate the X-ray scattering pattern, leading to the
      determination of their radius size distribution using (i) the generalized
      indirect Fourier transformation method, (ii) classical model fitting using SASfit
      and (iii) a Monte Carlo fitting approach using McSAS. The application of these
      three methods to the collected data sets from the various laboratories produces
      consistent mean number- and volume-weighted core radii of Rn = 2.76 (6) nm and Rv
      = 3.20 (4) nm, respectively. The corresponding widths of the lognormal radius
      distribution of the particles were sigman = 0.65 (1) nm and sigmav = 0.71 (1) nm.
      The particle concentration determined using this method was 3.0 (4) g l-1 or 4.2
      (7) * 10-6 mol l-1. These results are affected slightly by the choice of data
      evaluation procedure, but not by the instruments: the participating laboratories
      at synchrotron SAXS beamlines, commercial and in-house-designed instruments were
      all able to provide highly consistent data. This demonstrates that SAXS is a
      suitable method for revealing particle size distributions in the sub-20 nm region
      (at minimum), out of reach for most other analytical methods.

PMID- 29021733
TI  - Berkeley Screen: a set of 96 solutions for general macromolecular
      crystallization.
AB  - Using statistical analysis of the Biological Macromolecular Crystallization
      Database, combined with previous knowledge about crystallization reagents, a
      crystallization screen called the Berkeley Screen has been created. Correlating
      crystallization conditions and high-resolution protein structures, it is possible
      to better understand the influence that a particular solution has on protein
      crystal formation. Ions and small molecules such as buffers and precipitants used
      in crystallization experiments were identified in electron density maps,
      highlighting the role of these chemicals in protein crystal packing. The Berkeley
      Screen has been extensively used to crystallize target proteins from the Joint
      BioEnergy Institute and the Collaborative Crystallography program at the Berkeley
      Center for Structural Biology, contributing to several Protein Data Bank entries
      and related publications. The Berkeley Screen provides the crystallographic
      community with an efficient set of solutions for general macromolecular
      crystallization trials, offering a valuable alternative to the existing
      commercially available screens.

PMID- 29021734
TI  - Calibrating SANS data for instrument geometry and pixel sensitivity effects:
      access to an extended Q range.
AB  - An improved data-reduction procedure is proposed and demonstrated for small-angle
      neutron scattering (SANS) measurements. Its main feature is the correction of
      geometry- and wavelength-dependent intensity variations on the detector in a
      separate step from the different pixel sensitivities: the geometric and
      wavelength effects can be corrected analytically, while pixel sensitivities have
      to be calibrated to a reference measurement. The geometric effects are treated
      for position-sensitive 3He proportional counter tubes, where they are anisotropic
      owing to the cylindrical geometry of the gas tubes. For the calibration of pixel
      sensitivities, a procedure is developed that is valid for isotropic and
      anisotropic signals. The proposed procedure can save a significant amount of
      beamtime which has hitherto been used for calibration measurements.

PMID- 29021735
TI  - Quantifying adsorption-induced deformation of nanoporous materials on different
      length scales.
AB  - A new in situ setup combining small-angle neutron scattering (SANS) and
      dilatometry was used to measure water-adsorption-induced deformation of a
      monolithic silica sample with hierarchical porosity. The sample exhibits a
      disordered framework consisting of macropores and struts containing two
      dimensional hexagonally ordered cylindrical mesopores. The use of an H2O/D2O
      water mixture with zero scattering length density as an adsorptive allows a
      quantitative determination of the pore lattice strain from the shift of the
      corresponding diffraction peak. This radial strut deformation is compared with
      the simultaneously measured macroscopic length change of the sample with
      dilatometry, and differences between the two quantities are discussed on the
      basis of the deformation mechanisms effective at the different length scales. It
      is demonstrated that the SANS data also provide a facile way to quantitatively
      determine the adsorption isotherm of the material by evaluating the incoherent
      scattering contribution of H2O at large scattering vectors.

PMID- 29021736
TI  - Nanocrystallography measurements of early stage synthetic malaria pigment.
AB  - The recent availability of extremely intense, femtosecond X-ray free-electron
      laser (XFEL) sources has spurred the development of serial femtosecond
      nanocrystallography (SFX). Here, SFX is used to analyze nanoscale crystals of
      beta-hematin, the synthetic form of hemozoin which is a waste by-product of the
      malaria parasite. This analysis reveals significant differences in beta-hematin
      data collected during SFX and synchrotron crystallography experiments. To
      interpret these differences two possibilities are considered: structural
      differences between the nanocrystal and larger crystalline forms of beta-hematin,
      and radiation damage. Simulation studies show that structural inhomogeneity
      appears at present to provide a better fit to the experimental data. If
      confirmed, these observations will have implications for designing compounds that
      inhibit hemozoin formation and suggest that, for some systems at least,
      additional information may be gained by comparing structures obtained from
      nanocrystals and macroscopic crystals of the same molecule.

PMID- 29021737
TI  - BioXTAS RAW: improvements to a free open-source program for small-angle X-ray
      scattering data reduction and analysis.
AB  - BioXTAS RAW is a graphical-user-interface-based free open-source Python program
      for reduction and analysis of small-angle X-ray solution scattering (SAXS) data.
      The software is designed for biological SAXS data and enables creation and
      plotting of one-dimensional scattering profiles from two-dimensional detector
      images, standard data operations such as averaging and subtraction and analysis
      of radius of gyration and molecular weight, and advanced analysis such as
      calculation of inverse Fourier transforms and envelopes. It also allows easy
      processing of inline size-exclusion chromatography coupled SAXS data and data
      deconvolution using the evolving factor analysis method. It provides an
      alternative to closed-source programs such as Primus and ScAtter for primary data
      analysis. Because it can calibrate, mask and integrate images it also provides an
      alternative to synchrotron beamline pipelines that scientists can install on
      their own computers and use both at home and at the beamline.

PMID- 29021738
TI  - Erratum: Expanding Lorentz and spectrum corrections to large volumes of
      reciprocal space for single-crystal time-of-flight neutron diffraction.
      Corrigendum.
AB  - [This corrects the article DOI: 10.1107/S1600576716001369.].

PMID- 29021739
TI  - Effect of Error Augmentation on Brain Activation and Motor Learning of a Complex
      Locomotor Task.
AB  - Up to date, the functional gains obtained after robot-aided gait rehabilitation
      training are limited. Error augmenting strategies have a great potential to
      enhance motor learning of simple motor tasks. However, little is known about the
      effect of these error modulating strategies on complex tasks, such as relearning
      to walk after a neurologic accident. Additionally, neuroimaging evaluation of
      brain regions involved in learning processes could provide valuable information
      on behavioral outcomes. We investigated the effect of robotic training strategies
      that augment errors-error amplification and random force disturbance-and training
      without perturbations on brain activation and motor learning of a complex
      locomotor task. Thirty-four healthy subjects performed the experiment with a
      robotic stepper (MARCOS) in a 1.5 T MR scanner. The task consisted in tracking a
      Lissajous figure presented on a display by coordinating the legs in a gait-like
      movement pattern. Behavioral results showed that training without perturbations
      enhanced motor learning in initially less skilled subjects, while error
      amplification benefited better-skilled subjects. Training with error
      amplification, however, hampered transfer of learning. Randomly disturbing forces
      induced learning and promoted transfer in all subjects, probably because the
      unexpected forces increased subjects' attention. Functional MRI revealed main
      effects of training strategy and skill level during training. A main effect of
      training strategy was seen in brain regions typically associated with motor
      control and learning, such as, the basal ganglia, cerebellum, intraparietal
      sulcus, and angular gyrus. Especially, random disturbance and no perturbation
      lead to stronger brain activation in similar brain regions than error
      amplification. Skill-level related effects were observed in the IPS, in parts of
      the superior parietal lobe (SPL), i.e., precuneus, and temporal cortex. These
      neuroimaging findings indicate that gait-like motor learning depends on interplay
      between subcortical, cerebellar, and fronto-parietal brain regions. An
      interesting observation was the low activation observed in the brain's reward
      system after training with error amplification compared to training without
      perturbations. Our results suggest that to enhance learning of a locomotor task,
      errors should be augmented based on subjects' skill level. The impacts of these
      strategies on motor learning, brain activation, and motivation in neurological
      patients need further investigation.

PMID- 29021740
TI  - Electroacupuncture Alleviates Surgical Trauma-Induced Hypothalamus Pituitary
      Adrenal Axis Hyperactivity Via microRNA-142.
AB  - Electroacupuncture (EA) could improve the hyperactivity of the hypothalamus
      pituitary adrenal (HPA) axis induced by hepatectomy. However, its underlying
      mechanism still remains largely unclear. Here, we found that hypothalamic
      corticotrophin releasing hormone (CRH) modulates the function of the HPA axis,
      while hepatectomy induced an HPA axis disorder and EA application could regulate
      the hypothalamic CRH. We first demonstrated that microRNAs (miRNAs) target on CRH
      via bioinformatics analysis and screened them in the primary hypothalamic
      neurons. MicroR-142 (miR-142) and miR-376c were identified to inhibit CRH at the
      mRNA and protein levels, and a dual luciferase reporter assay confirmed their
      binding to the 3'-untranslated regions (3'-UTR) of CRH. Further analyses revealed
      a decrease in hypothalamic miR-142 expression in the hepatectomy rats and an
      increase in miR-142 and miR-376c after EA intervention. Importantly, the
      improvement effect of EA on the HPA axis regulatory function in hepatectomy rats
      was blocked by miR-142 antagomir. Our findings illustrated that EA could up
      regulate hypothalamic miR-142 expression and decrease the CRH level to alleviate
      the hyperactivity of the HPA axis induced by hepatectomy.

PMID- 29021743
TI  - Resolving Astrocyte Heterogeneity in the CNS.
AB  - Astrocytes play essential roles in nearly all aspects of brain function from
      modulating synapses and neurovasculature to preserving appropriate extracellular
      solute concentrations. To meet the complex needs of the central nervous system
      (CNS), astrocytes possess highly specialized properties that are optimized for
      their surrounding neural circuitry. Precisely how these diverse astrocytes types
      are generated in vivo, however, remains poorly understood. Key to this process is
      a critical balance of intrinsic developmental patterning and context-dependent
      environmental signaling events that configures astrocyte phenotype. Indeed,
      emerging lines of evidence indicate that persistent cues from neighboring cells
      in the mature CNS cooperate with early patterning events to promote astrocyte
      diversity. Consistent with this, manipulating Sonic hedgehog (Shh), Notch and
      fibroblast growth factor (FGF) signaling in the adult brain, have profound
      effects on the structural, morphological and physiological state of mature
      astrocytes. These pathways may become disrupted in various neurological diseases
      and contribute to CNS pathology. This mini-review article focuses on how context
      dependent environmental cues cooperate with intrinsic developmental patterning
      events to control astrocyte diversity in vivo in order to promote healthy brain
      function.

PMID- 29021742
TI  - Neuroprotective Mechanisms of Lycium barbarum Polysaccharides Against Ischemic
      Insults by Regulating NR2B and NR2A Containing NMDA Receptor Signaling Pathways.
AB  - Glutamate excitotoxicity plays an important role in neuronal death after
      ischemia. However, all clinical trials using glutamate receptor inhibitors have
      failed. This may be related to the evidence that activation of different subunit
      of NMDA receptor will induce different effects. Many studies have shown that
      activation of the intrasynaptic NR2A subunit will stimulate survival signaling
      pathways, whereas upregulation of extrasynaptic NR2B will trigger apoptotic
      pathways. A Lycium barbarum polysaccharide (LBP) is a mixed compound extracted
      from Lycium barbarum fruit. Recent studies have shown that LBP protects neurons
      against ischemic injury by anti-oxidative effects. Here we first reported that
      the effect of LBP against ischemic injury can be achieved by regulating NR2B and
      NR2A signaling pathways. By in vivo study, we found LBP substantially reduced CA1
      neurons from death after transient global ischemia and ameliorated memory deficit
      in ischemic rats. By in vitro study, we further confirmed that LBP increased the
      viability of primary cultured cortical neurons when exposed to oxygen-glucose
      deprivation (OGD) for 4 h. Importantly, we found that LBP antagonized increase in
      expression of major proteins in the NR2B signal pathway including NR2B, nNOS, Bcl
      2-associated death promoter (BAD), cytochrome C (cytC) and cleaved caspase-3, and
      also reduced ROS level, calcium influx and mitochondrial permeability after 4 h
      OGD. In addition, LBP prevented the downregulation in the expression of NR2A,
      pAkt and pCREB, which are important cell survival pathway components.
      Furthermore, LBP attenuated the effects of a NR2B co-agonist and NR2A inhibitor
      on cell mortality under OGD conditions. Taken together, our results demonstrated
      that LBP is neuroprotective against ischemic injury by its dual roles in
      activation of NR2A and inhibition of NR2B signaling pathways, which suggests that
      LBP may be a superior therapeutic candidate for targeting glutamate
      excitotoxicity for the treatment of ischemic stroke.

PMID- 29021741
TI  - The Neuroprotective Role of Protein Quality Control in Halting the Development of
      Alpha-Synuclein Pathology.
AB  - Synucleinopathies are a family of neurodegenerative disorders that comprises
      Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Each
      of these disorders is characterized by devastating motor, cognitive, and
      autonomic consequences. Current treatments for synucleinopathies are not curative
      and are limited to improvement of quality of life for affected individuals.
      Although the underlying causes of these diseases are unknown, a shared
      pathological hallmark is the presence of proteinaceous inclusions containing the
      alpha-synuclein (alpha-syn) protein in brain tissue. In the past few years, it
      has been proposed that these inclusions arise from the self-templated, prion-like
      spreading of misfolded and aggregated forms of alpha-syn throughout the brain,
      leading to neuronal dysfunction and death. In this review, we describe how
      impaired protein homeostasis is a prominent factor in the alpha-syn aggregation
      cascade, with alterations in protein quality control (PQC) pathways observed in
      the brains of patients. We discuss how PQC modulates alpha-syn accumulation,
      misfolding and aggregation primarily through chaperoning activity, proteasomal
      degradation, and lysosome-mediated degradation. Finally, we provide an overview
      of experimental data indicating that targeting PQC pathways is a promising avenue
      to explore in the design of novel neuroprotective approaches that could impede
      the spreading of alpha-syn pathology and thus provide a curative treatment for
      synucleinopathies.

PMID- 29021745
TI  - Tyramine Actions on Drosophila Flight Behavior Are Affected by a Glial
      Dehydrogenase/Reductase.
AB  - The biogenic amines octopamine (OA) and tyramine (TA) modulate insect motor
      behavior in an antagonistic manner. OA generally enhances locomotor behaviors
      such as Drosophila larval crawling and flight, whereas TA decreases locomotor
      activity. However, the mechanisms and cellular targets of TA modulation of
      locomotor activity are incompletely understood. This study combines
      immunocytochemistry, genetics and flight behavioral assays in the Drosophila
      model system to test the role of a candidate enzyme for TA catabolism, named
      Nazgul (Naz), in flight motor behavioral control. We hypothesize that the
      dehydrogenase/reductase Naz represents a critical step in TA catabolism.
      Immunocytochemistry reveals that Naz is localized to a subset of Repo positive
      glial cells with cell bodies along the motor neuropil borders and numerous
      positive Naz arborizations extending into the synaptic flight motor neuropil.
      RNAi knock down of Naz in Repo positive glial cells reduces Naz protein level
      below detection level by Western blotting. The resulting consequence is a
      reduction in flight durations, thus mimicking known motor behavioral phenotypes
      as resulting from increased TA levels. In accord with the interpretation that
      reduced TA degradation by Naz results in increased TA levels in the flight motor
      neuropil, the motor behavioral phenotype can be rescued by blocking TA receptors.
      Our findings indicate that TA modulates flight motor behavior by acting on
      central circuitry and that TA is normally taken up from the central motor
      neuropil by Repo-positive glial cells, desaminated and further degraded by Naz.

PMID- 29021746
TI  - Lever Insertion as a Salient Stimulus Promoting Insensitivity to Outcome
      Devaluation.
AB  - Flexible and efficient decision-making in complex environments can be achieved
      through constant interactions between the goal-directed and habitual systems.
      While goal-directed behavior is considered dependent upon Response-Outcome (R-O)
      associations, habits instead rely on Stimulus-Response (S-R) associations.
      However, the stimuli that support the S-R association underlying habitual
      responding in typical instrumental procedures are poorly defined. To resolve this
      issue, we designed a discrete-trials procedure, in which rats must wait for lever
      insertion and complete a sequence of five lever presses to obtain a reward (20%
      sucrose or grain-based pellets). Lever insertion thus constituted an audio-visual
      stimulus signaling the opportunity for reward. Using sensory-specific satiety
      induced devaluation, we found that rats trained with grain-based pellets remained
      sensitive to outcome devaluation over the course of training with this procedure
      whereas rats trained with a solution of 20% sucrose rapidly developed habit, and
      that insensitivity to outcome devaluation in rats trained with sucrose did not
      result from a bias in general satiety. Importantly, although rats trained with
      pellets were sensitive to satiety-induced devaluation, their performance was not
      affected by degradation of instrumental contingency and devaluation by
      conditioned taste aversion (CTA), suggesting that these rats may also have
      developed habitual responding. To test whether the discrete-trials procedure
      biases subjects towards habitual responding, we compared discrete-trials to free
      running instrumental responding, and found that rats trained with sucrose in a
      fixed-ratio 5 (FR5) procedure with continuous presentation of the lever were goal
      directed. Together, these results demonstrate that discrete presentations of a
      stimulus predictive of reward availability promoted the formation of S-R habit in
      rats trained with liquid sucrose. Further research is necessary to explain
      inconsistencies in sensitivity to outcome devaluation when rats are trained with
      grain-based pellets.

PMID- 29021744
TI  - Posterior Thalamic Nucleus Modulation of Tactile Stimuli Processing in Rat Motor
      and Primary Somatosensory Cortices.
AB  - Rodents move rhythmically their facial whiskers and compute differences between
      signals predicted and those resulting from the movement to infer information
      about objects near their head. These computations are carried out by a large
      network of forebrain structures that includes the thalamus and the primary
      somatosensory (S1BF) and motor (M1wk) cortices. Spatially and temporally precise
      mechanorreceptive whisker information reaches the S1BF cortex via the
      ventroposterior medial thalamic nucleus (VPM). Other whisker-related information
      may reach both M1wk and S1BF via the axons from the posterior thalamic nucleus
      (Po). However, Po axons may convey, in addition to direct sensory signals, the
      dynamic output of computations between whisker signals and descending motor
      commands. It has been proposed that this input may be relevant for adjusting
      cortical responses to predicted vs. unpredicted whisker signals, but the effects
      of Po input on M1wk and S1BF function have not been directly tested or compared
      in vivo. Here, using electrophysiology, optogenetics and pharmacological tools,
      we compared in adult rats M1wk and S1BF in vivo responses in the whisker areas of
      the motor and primary somatosensory cortices to passive multi-whisker deflection,
      their dependence on Po activity, and their changes after a brief intense
      activation of Po axons. We report that the latencies of the first component of
      tactile-evoked local field potentials in M1wk and S1BF are similar. The evoked
      potentials decrease markedly in M1wk, but not in S1BF, by injection in Po of the
      GABAA agonist muscimol. A brief high-frequency electrical stimulation of Po
      decreases the responsivity of M1wk and S1BF cells to subsequent whisker
      stimulation. This effect is prevented by the local application of omega-agatoxin,
      suggesting that it may in part depend on GABA release by fast-spiking parvalbumin
      (PV)-expressing cortical interneurons. Local optogenetic activation of Po
      synapses in different cortical layers also diminishes M1wk and S1BF responses.
      This effect is most pronounced in the superficial layers of both areas, known to
      be the main source and target of their reciprocal cortico-cortical connections.

PMID- 29021747
TI  - Hyperbaric Oxygen Environment Can Enhance Brain Activity and Multitasking
      Performance.
AB  - Background: The Brain uses 20% of the total oxygen supply consumed by the entire
      body. Even though, <10% of the brain is active at any given time, it utilizes
      almost all the oxygen delivered. In order to perform complex tasks or more than
      one task (multitasking), the oxygen supply is shifted from one brain region to
      another, via blood perfusion modulation. The aim of the present study was to
      evaluate whether a hyperbaric oxygen (HBO) environment, with increased oxygen
      supply to the brain, will enhance the performance of complex and/or multiple
      activities. Methods: A prospective, double-blind randomized control, crossover
      trial including 22 healthy volunteers. Participants were asked to perform a
      cognitive task, a motor task and a simultaneous cognitive-motor task
      (multitasking). Participants were randomized to perform the tasks in two
      environments: (a) normobaric air (1 ATA 21% oxygen) (b) HBO (2 ATA 100% oxygen).
      Two weeks later participants were crossed to the alternative environment.
      Blinding of the normobaric environment was achieved in the same chamber with
      masks on while hyperbaric sensation was simulated by increasing pressure in the
      first minute and gradually decreasing to normobaric environment prior to tasks
      performance. Results: Compared to the performance at normobaric conditions, both
      cognitive and motor single tasks scores were significantly enhanced by HBO
      environment (p < 0.001 for both). Multitasking performance was also significantly
      enhanced in HBO environment (p = 0.006 for the cognitive part and p = 0.02 for
      the motor part). Conclusions: The improvement in performance of both single and
      multi-tasking while in an HBO environment supports the hypothesis which according
      to, oxygen is indeed a rate limiting factor for brain activity. Hyperbaric
      oxygenation can serve as an environment for brain performance. Further studies
      are needed to evaluate the optimal oxygen levels for maximal brain performance.

PMID- 29021748
TI  - Binge-Like Sucrose Self-Administration Experience Inhibits Cocaine and Sucrose
      Seeking Behavior in Offspring.
AB  - Recent studies show that emotional and environmental stimuli promote epigenetic
      inheritance and influence behavioral development in the subsequent generations.
      Caloric mal- and under-nutrition has been shown to cause metabolic disturbances
      in the subsequent generation, but the incentive properties of paternal binge-like
      eating in offspring is still unknown. Here we show that paternal sucrose self
      administration experience could induce inter-generational decrease in both
      sucrose and cocaine-seeking behavior, and sucrose responding in F1 rats, but not
      F2, correlated with the performance of F0 rats in sucrose self-administration.
      Higher anxiety level and decreased cocaine sensitivity were observed in Sucrose
      F1 compared with Control F1, possibly contributing to the desensitization
      phenotype in cocaine and sucrose self-administration. Our study revealed that
      paternal binge-like sucrose consumption causes decrease in reward seeking and
      induces anxiety-like behavior in the F1 offspring.

PMID- 29021749
TI  - Phase-Dependent Modulation of Signal Transmission in Cortical Networks through
      tACS-Induced Neural Oscillations.
AB  - Oscillatory neural activity is considered a basis of signal transmission in brain
      networks. However, the causal role of neural oscillations in regulating cortico
      cortical signal transmission has so far not been directly demonstrated. To date,
      due to methodological limitations, studies on the online modulatory mechanisms of
      transcranial alternating current stimulation (tACS)-induced neural oscillations
      are confined to the primary motor cortex. To address the causal role of
      oscillatory activity in modulating cortico-cortical signal transmission, we have
      established a new method using concurrent tACS, transcranial magnetic stimulation
      (TMS) and electroencephalography (EEG). Through tACS, we introduced 6-Hz (theta)
      oscillatory activity in the human dorsolateral prefrontal cortex (DLPFC). During
      tACS, we applied single-pulse TMS over the DLPFC at different phases of tACS and
      assessed propagation of TMS-induced neural activity with EEG. We show that tACS
      induced theta oscillations modulate the propagation of TMS-induced activity in a
      phase-dependent manner and that phase-dependent modulation is not simply
      explained by the instantaneous amplitude of tACS. The results demonstrate a phase
      dependent modulatory mechanism of tACS at a cortical network level, which is
      consistent with a causal role of neural oscillations in regulating the efficacy
      of signal transmission in the brain.

PMID- 29021751
TI  - Language Learning Variability within the Dorsal and Ventral Streams as a Cue for
      Compensatory Mechanisms in Aphasia Recovery.
AB  - Dorsal and ventral pathways connecting perisylvian language areas have been shown
      to be functionally and anatomically segregated. Whereas the dorsal pathway
      integrates the sensory-motor information required for verbal repetition, the
      ventral pathway has classically been associated with semantic processes. The
      great individual differences characterizing language learning through life partly
      correlate with brain structure and function within these dorsal and ventral
      language networks. Variability and plasticity within these networks also underlie
      inter-individual differences in the recovery of linguistic abilities in aphasia.
      Despite the division of labor of the dorsal and ventral streams, studies in
      healthy individuals have shown how the interaction of them and the redundancy in
      the areas they connect allow for compensatory strategies in functions that are
      usually segregated. In this mini-review we highlight the need to examine
      compensatory mechanisms between streams in healthy individuals as a helpful guide
      to choosing the most appropriate rehabilitation strategies, using spared
      functions and targeting preserved compensatory networks for brain plasticity.

PMID- 29021752
TI  - Potential Impact of Geomagnetic Field in Transcranial Magnetic Stimulation for
      the Treatment of Neurodegenerative Diseases.
AB  - Throughout the long history of various therapeutic trials of transcranial
      magnetic stimulation (TMS), some TMS protocols have been reported to be clearly
      effective in the treatment of neurodegenerative diseases. Despite promising
      results from repetitive TMS (rTMS) using low frequency electromagnetic fields
      (EMFs) for neurodegenerative diseases, the low reproducibility has hampered the
      clinical applications of rTMS. Here, based on the notion of radical pair
      mechanism explaining magnetoreception in living organisms, we propose a new
      perspective that rTMS with controlled geomagnetic field (rTMS-GMF) can be an
      efficient and reproducible therapeutic approach for neurodegenerative diseases.
      In addition, combined consideration of imprinted GMF and/or EMFs in patients'
      earlier life may augment the potential efficacy of the rTMS-GMF. The
      investigation of this approach is intriguing and may have a high impact on the
      technical suitability and clinical application of the rTMS-GMF in the near
      future.

PMID- 29021753
TI  - Improving the Robustness of Electromyogram-Pattern Recognition for Prosthetic
      Control by a Postprocessing Strategy.
AB  - Electromyogram (EMG) contains rich information for motion decoding. As one of its
      major applications, EMG-pattern recognition (PR)-based control of prostheses has
      been proposed and investigated in the field of rehabilitation robotics for
      decades. These prostheses can offer a higher level of dexterity compared to the
      commercially available ones. However, limited progress has been made toward
      clinical application of EMG-PR-based prostheses, due to their unsatisfactory
      robustness against various interferences during daily use. These interferences
      may lead to misclassifications of motion intentions, which damage the control
      performance of EMG-PR-based prostheses. A number of studies have applied methods
      that undergo a postprocessing stage to determine the current motion outputs,
      based on previous outputs or other information, which have proved effective in
      reducing erroneous outputs. In this study, we proposed a postprocessing strategy
      that locks the outputs during the constant contraction to block out occasional
      misclassifications, upon detecting the motion onset using a threshold. The
      strategy was investigated using three different motion onset detectors, namely
      mean absolute value, Teager-Kaiser energy operator, or mechanomyogram (MMG). Our
      results indicate that the proposed strategy could suppress erroneous outputs,
      during rest and constant contractions in particular. In addition, with MMG as the
      motion onset detector, the strategy was found to produce the most significant
      improvement in the performance, reducing the total errors up to around 50% (from
      22.9 to 11.5%) in comparison to the original classification output in the online
      test, and it is the most robust against threshold value changes. We speculate
      that motion onset detectors that are both smooth and responsive would further
      enhance the efficacy of the proposed postprocessing strategy, which would
      facilitate the clinical application of EMG-PR-based prosthetic control.

PMID- 29021750
TI  - Cough-Anal Reflex May Be the Expression of a Pre-Programmed Postural Action.
AB  - When coughing, an involuntary contraction of the external anal sphincter occurs,
      in order to prevent unwanted leakages or sagging of the pelvis muscular wall.
      Literature originally described such cough-anal response as a reflex elicited by
      cough, therefore identifying a precise cause-effect relationship. However, recent
      studies report that the anal contraction actually precedes the rise in abdominal
      pressure during cough expiratory effort, so that the sphincter activity should be
      pre-programmed. In recent years, an important family of pre-programmed muscle
      activities has been well documented to precede voluntary movements: these
      anticipatory actions play a fundamental role in whole body and segmental postural
      control, hence they are referred to as anticipatory postural adjustments (APAs).
      On these basis, we searched in literature for similarities between APAs and the
      cough-anal response, observing that both follow the same predictive homeostatic
      principle, namely that anticipatory collateral actions are needed to prevent the
      unwanted mechanical consequences induced by the primary movement. We thus propose
      that the cough-anal response also belongs to the family of pre-programmed
      actions, as it may be interpreted as an APA acting on the abdominal-thoracic
      compartment; in other words, the cough-anal response may actually be an
      Anticipatory Sphincter Adjustment, the visceral counterpart of APAs.

PMID- 29021754
TI  - Lower Performance in Orientation to Time and Place Associates with Greater Risk
      of Cardiovascular Events and Mortality in the Oldest Old: Leiden 85-Plus Study.
AB  - Background: Impairment in orientation to time and place is commonly observed in
      community-dwelling older individuals. Nevertheless, the clinical significance of
      this has been not fully explored. In this study, we investigated the link between
      performance in orientation domains and future risk of cardiovascular events and
      mortality in a non-hospital setting of the oldest old adults. Methods: We
      included 528 subjects free of myocardial infarction (Group A), 477 individuals
      free of stroke/transient ischemic attack (Group B), and 432 subjects free of both
      myocardial infarction and stroke/transient ischemic attack (Group C) at baseline
      from the population-based Leiden 85-plus cohort study. Participants were asked to
      answer five questions related to orientation to time and five questions related
      to orientation to place. 5-year risks of first-time fatal and non-fatal
      myocardial infarction, fatal and non-fatal stroke, as well as cardiovascular and
      non-cardiovascular mortality, were estimated using the multivariate Cox
      regression analysis. Results: In the multivariable analyses, adjusted for
      sociodemographic characteristics and cardiovascular risk factors, each point
      lower performance in "orientation to time" was significantly associated with
      higher risk of first-time myocardial infarction (hazard ratio [HR] 1.35, 95%
      confidence interval [CI] 1.09-1.67, P = 0.007), first-time stroke (HR 1.35, 95%
      CI 1.12-1.64, P = 0.002), cardiovascular mortality (HR 1.28, 95% CI 1.06-1.54, P
      = 0.009) and non-cardiovascular mortality (HR 1.37, 95% CI 1.20-1.56, P < 0.001).
      Similarly, each point lower performance in "orientation to place" was
      significantly associated with higher risk of first-time myocardial infarction (HR
      1.67, 95% CI 1.25-2.22, P = 0.001), first-time stroke (HR 1.39, 95% CI 1.05-1.82,
      P = 0.016), cardiovascular mortality (HR 1.35, 95% CI 1.00-1.82, P = 0.054) and
      non-cardiovascular mortality (HR 1.45, 95% CI 1.20-1.77, P < 0.001). Conclusions:
      Lower performance in orientation to time and place in advanced age is
      independently related to higher risk of myocardial infarction, stroke and
      mortality. Impaired orientation might be an early sign of covert vascular
      injuries, putting subjects at greater risk of cardiovascular events and
      mortality.

PMID- 29021755
TI  - DJ-1 Inhibits alpha-Synuclein Aggregation by Regulating Chaperone-Mediated
      Autophagy.
AB  - alpha-Synuclein misfolding and aggregation play an important role in the
      pathogenesis of Parkinson's disease (PD). Loss of function and mutation of the
      PARK7/DJ-1 gene cause early-onset familial PD. DJ-1 can inhibit alpha-synuclein
      aggregation, and may function at an early step in the aggregation process.
      Soluble wild-type (WT) alpha-synuclein is mainly degraded by chaperone-mediated
      autophagy (CMA), and impairment of CMA is closely related to the pathogenesis of
      PD. Here, we investigated whether DJ-1 could reduce alpha-synuclein accumulation
      and aggregation by CMA. DJ-1 knockout mice and DJ-1 siRNA knockdown SH-SY5Y cells
      were used to investigate the potential mechanisms underlying the relationship
      between DJ-1 deficiency and alpha-synuclein aggregation. First, we confirmed that
      DJ-1 deficiency increased the accumulation and aggregation of alpha-synuclein in
      both SH-SY5Y cells and PD animal models, and overexpression of DJ-1 in vitro
      effectively decreased alpha-synuclein levels. alpha-Synuclein overexpression
      activated CMA by elevating the levels of lysosome-associated membrane protein
      type-2A (LAMP2A), but DJ-1 deficiency suppressed upregulation of LAMP2A. DJ-1
      deficiency downregulated the level of lysosomal 70 kDa heat-shock cognate protein
      (HSC70) but not the levels of that in homogenates. Further studies showed that DJ
      1 deficiency accelerated the degradation of LAMP2A in lysosomes, leading to the
      aggregation of alpha-synuclein. Our study suggests that DJ-1 deficiency
      aggravates alpha-synuclein aggregation by inhibiting the activation of CMA and
      provides further evidence of the molecular interaction between PD-related
      proteins via the CMA pathway.

PMID- 29021757
TI  - Cerebral Small Vessel Disease Burden Is Associated with Motor Performance of
      Lower and Upper Extremities in Community-Dwelling Populations.
AB  - Objective: To investigate the correlation between cerebral small vessel disease
      (CSVD) burden and motor performance of lower and upper extremities in community
      dwelling populations. Methods: We performed a cross-sectional analysis on 770
      participants enrolled in the Shunyi study, which is a population-based cohort
      study. CSVD burden, including white matter hyperintensities (WMH), lacunes,
      cerebral microbleeds (CMBs), perivascular spaces (PVS), and brain atrophy were
      measured using 3T magnetic resonance imaging. All participants underwent
      quantitative motor assessment of lower and upper extremities, which included 3-m
      walking speed, 5-repeat chair-stand time, 10-repeat pronation-supination time,
      and 10-repeat finger-tapping time. Data on demographic characteristics, vascular
      risk factors, and cognitive functions were collected. General linear model
      analysis was performed to identify potential correlations between motor
      performance measures and imaging markers of CSVD after controlling for
      confounding factors. Results: For motor performance of the lower extremities, WMH
      was negatively associated with gait speed (standardized beta = -0.092, p = 0.022)
      and positively associated with chair-stand time (standardized beta = 0.153, p <
      0.0001, surviving FDR correction). For motor performance of the upper
      extremities, pronation-supination time was positively associated with WMH
      (standardized beta = 0.155, p < 0.0001, surviving FDR correction) and negatively
      with brain parenchymal fraction (BPF; standardized beta = -0.125, p = 0.011,
      surviving FDR correction). Only BPF was found to be negatively associated with
      finger-tapping time (standardized beta = -0.123, p = 0.012). However, lacunes,
      CMBs, or PVS were not found to be associated with motor performance of lower or
      upper extremities in multivariable analysis. Conclusion: Our findings suggest
      that cerebral microstructural changes related to CSVD may affect motor
      performance of both lower and upper extremities. WMH and brain atrophy are most
      strongly associated with motor function deterioration in community-dwelling
      populations.

PMID- 29021756
TI  - Expression of Tau Pathology-Related Proteins in Different Brain Regions: A
      Molecular Basis of Tau Pathogenesis.
AB  - Microtubule-associated protein tau is hyperphosphorylated and aggregated in
      affected neurons in Alzheimer disease (AD) brains. The tau pathology starts from
      the entorhinal cortex (EC), spreads to the hippocampus and frontal and temporal
      cortices, and finally to all isocortex areas, but the cerebellum is spared from
      tau lesions. The molecular basis of differential vulnerability of different brain
      regions to tau pathology is not understood. In the present study, we analyzed
      brain regional expressions of tau and tau pathology-related proteins. We found
      that tau was hyperphosphorylated at multiple sites in the frontal cortex (FC),
      but not in the cerebellum, from AD brain. The level of tau expression in the
      cerebellum was about 1/4 of that seen in the frontal and temporal cortices in
      human brain. In the rat brain, the expression level of tau with three microtubule
      binding repeats (3R-tau) was comparable in the hippocampus, EC, FC, parietal
      temporal cortex (PTC), occipital-temporal cortex (OTC), striatum, thalamus,
      olfactory bulb (OB) and cerebellum. However, the expression level of 4R-tau was
      the highest in the EC and the lowest in the cerebellum. Tau phosphatases,
      kinases, microtubule-related proteins and other tau pathology-related proteins
      were also expressed in a region-specific manner in the rat brain. These results
      suggest that higher levels of tau and tau kinases in the EC and low levels of
      these proteins in the cerebellum may accounts for the vulnerability and
      resistance of these representative brain regions to the development of tau
      pathology, respectively. The present study provides the regional expression
      profiles of tau and tau pathology-related proteins in the brain, which may help
      understand the brain regional vulnerability to tau pathology in neurodegenerative
      tauopathies.

PMID- 29021758
TI  - Acute Neuromuscular Adaptations in the Postural Control of Patients with
      Parkinson's Disease after Perturbed Walking.
AB  - Patients suffering from Parkinson's disease (PD) present motor impairments
      reflected in the dynamics of the center of pressure (CoP) adjustments during
      quiet standing. One method to study the dynamics of CoP adjustments is the
      entropic half-life (EnHL), which measures the short-term correlations of a time
      series at different time scales. Changes in the EnHL of CoP time series suggest
      neuromuscular adaptations in the control of posture. In this study, we sought to
      investigate the immediate changes in the EnHL of CoP adjustments of patients with
      PD during one session of perturbed (experimental group) and unperturbed treadmill
      walking (control group). A total of 39 patients with PD participated in this
      study. The experimental group (n = 19) walked on a treadmill providing small
      tilting of the treadmill platform. The control group (n = 20) walked without
      perturbations. Each participant performed 5-min practice followed by three 5-min
      training blocks of walking with or without perturbation (with 3-min resting in
      between). Quiet standing CoP data was collected for 30 s at pre-training, after
      each training block, immediately post-training, and after 10 min retention. The
      EnHL was computed on the original and surrogates (phase-randomized) CoP signals
      in the medio-lateral (ML) and anterior-posterior (AP) directions. Data was
      analyzed using four-way mixed ANOVA. Increased EnHL values were observed for both
      groups (Time effect, p < 0.001) as the intervention progressed, suggesting
      neuromuscular adaptations in the control of posture. The EnHL of surrogate
      signals were significantly lower than for original signals (p < 0.001),
      confirming that these adaptations come from non-random control processes. There
      was no Group effect (p = 0.622), however by analyzing the significant Group by
      Direction by Time interaction (p < 0.05), a more pronounced effect in the ML
      direction of the perturbed group was observed. Altogether, our findings show that
      treadmill walking decreases the complexity of CoP adjustments, suggesting
      neuromuscular adaptations in balance control during a short training period.
      Further investigations are required to assess these adaptations during longer
      training intervals.

PMID- 29021759
TI  - Effects of Gladiolus dalenii on the Stress-Induced Behavioral, Neurochemical, and
      Reproductive Changes in Rats.
AB  - Gladiolus dalenii is a plant commonly used in many regions of Cameroon as a cure
      for various diseases like headaches, epilepsy, schizophrenia, and mood disorders.
      Recent studies have revealed that the aqueous extract of G. dalenii (AEGD)
      exhibited antidepressant-like properties in rats. Therefore, we hypothesized that
      the AEGD could protect from the stress-induced behavioral, neurochemical, and
      reproductive changes in rats. The objective of the present study was to elucidate
      the effect of the AEGD on behavioral, neurochemical, and reproductive
      characteristics, using female rats subjected to chronic immobilization stress.
      The chronic immobilization stress (3 h per day for 28 days) was applied to induce
      female reproductive and behavioral impairments in rats. The immobilization stress
      was provoked in rats by putting them separately inside cylindrical restrainers
      with ventilated doors at ambient temperature. The plant extract was given to rats
      orally everyday during 28 days, 5 min before induction of stress. On a daily
      basis, a vaginal smear was made to assess the duration of the different phases of
      the estrous cycle and at the end of the 28 days of chronic immobilization stress,
      the rat's behavior was assessed in the elevated plus maze. They were sacrificed
      by cervical disruption. The organs were weighed, the ovary histology done, and
      the biochemical parameters assessed. The findings of this research revealed that
      G. dalenii increased the entries and the time of open arm exploration in the
      elevated plus maze. Evaluation of the biochemical parameters levels indicated
      that there was a significant reduction in the corticosterone, progesterone, and
      prolactin levels in the G. dalenii aqueous extract treated rats compared to
      stressed rats whereas the levels of serotonin, triglycerides, adrenaline,
      cholesterol, glucose estradiol, follicle stimulating hormone and luteinizing
      hormone were significantly increased in the stressed rats treated with, G.
      dalenii, diazepam and in co-administration of the plant extract and diazepam
      treated rats. Moreover stressed rats showed significant changes in estrous cycle
      phases compared to vehicle control and these changes of the estrous cycle were
      less in the rats treated with G. dalenii compared to the negative control rats.
      G. dalenii extract showed antagonizing effects on the stress-induced
      reproductive, behavioral, and neurochemical changes. These effects could be
      related to the bioactive molecules and secondary metabolites like alkaloids and
      flavonoids in the plant.

PMID- 29021760
TI  - Saponins and Flavonoids from Adzuki Bean (Vigna angularis L.) Ameliorate High-Fat
      Diet-Induced Obesity in ICR Mice.
AB  - Background and purpose: As an herbal medicine, adzuki bean has been practiced
      since the Tang Dynasty of China to maintain health and control weight; this
      practice is still very popular in China nowadays. However, it is still lack of
      sufficient scientific basis to explain scientific principle of this popular civil
      practice in weight control using adzuki bean. The purpose of this study was to
      verify and explain the anti-obesity effects of adzuki bean through in vitro
      enzymatic assays, in vitro lipolysis and in vivo study of obese mice model.
      Methods: Inhibitory effects of flavonoids and saponins from adzuki bean (Vigna
      angularis) on pancreatic lipase, alpha-glucosidase activities, and noradrenaline
      induced lipolysis were assessed. High-fat diet-induced obesity model was created
      to study anti-obesity effects of adzuki bean. Both serum and liver lipid
      parameters were determined after 8 weeks intervention. Results: Adzuki bean
      extracts enhanced lipolysis. Compared to the final body weight of high-fat diet
      group, oral administration of adzuki bean significantly (p < 0.05) reduced the
      final body weight of mice and adipose tissue accumulation. The adzuki bean
      intervention also significantly reduced the levels of serum triglyceride, total
      cholesterol, low density lipoprotein-cholesterol, and liver lipid. Conclusion:
      Adzuki bean demonstrated the anti-obesity effects on mice, such effects may
      mediated through the inhibitory effects of flavonoids and saponins from adzuki
      bean on alpha-glucosidase and pancreatic lipase activities, and lipolysis
      enhancement effect of active components from adzuki bean.

PMID- 29021761
TI  - Protective Effects of Sodium (+/-)-5-Bromo-2-(alpha-Hydroxypentyl) Benzoate in a
      Rodent Model of Global Cerebral Ischemia.
AB  - The aim of the current study was to explore the protective effects of sodium (+/
      )-5-bromo-2-(alpha-hydroxypentyl) benzoate (brand name: brozopine, BZP) in a rat
      model of global cerebral ischemia. The rat model was established using a modified
      Winocur's method; close postoperative observation was conducted at all times.
      Neurological function was detected through prehensile traction and beam-walking
      test. BZP reduced mortality and prolonged the survival time of rats with global
      cerebral ischemia, within 24 h. There was a decreased survival rate (60%) in the
      Model group, while the survival rate of the BZP (3 and 12 mg/kg) remarkably
      increased the survival rate (to 80 and 90%, respectively), in a dose-dependent
      manner. Compared with the Model group (survival time: 18.50 h), the
      administration of BZP (0.75, 3, and 12 mg/kg) prolonged the survival time (to
      20.38, 21.85, and 23.90 h, respectively), particularly in BZP 12 mg/kg group (P <
      0.05). Additionally, the BZP (12 mg/kg) group exhibited an improvement in their
      motor function (P < 0.05). The BZP groups (0.75, 3, and 12 mg/kg) displayed
      significantly reduced necrosis and the percentage of apoptotic cells (P < 0.05
      and P < 0.01, respectively). Compared with Model group, BZP (0.75, 3, and 12
      mg/kg) increased the NeuN optical density values (P < 0.01). Rats with global
      ischemia had a high expression of Cyt-c, caspase-3, and the Bax/Bcl-2 ratio
      compared with sham group (P < 0.01). BZP (0.75, 3, and 12 mg/kg), however,
      reduced the expression of Cyt-c, caspase-3, and the Bax/Bcl-2 ratio, in a dose
      dependent manner (P < 0.01). There was low expression of p-Akt and PI3K in Model
      group, compared with the sham group (P < 0.01). Meanwhile, BZP (0.75, 3, and 12
      mg/kg) increased the expression of p-Akt and PI3K in a dose-dependent manner (P <
      0.01). We also found the expression of Cyt-c, caspase-3, Bax/Bcl-2 ratio, PI3K, p
      Akt, and comprehensive score were directly related. In conclusion, BZP had
      therapeutic potential and prevented stroke in rat model of global cerebral
      ischemia. The underlying mechanisms may be related to the inhibition of apoptosis
      and activation of the survival-signaling-pathway.

PMID- 29021762
TI  - Massage Alleviates Delayed Onset Muscle Soreness after Strenuous Exercise: A
      Systematic Review and Meta-Analysis.
AB  - Purpose: The purpose of this systematic review and meta-analysis was to evaluate
      the effects of massage on alleviating delayed onset of muscle soreness (DOMS) and
      muscle performance after strenuous exercise. Method: Seven databases consisting
      of PubMed, Embase, EBSCO, Cochrane Library, Web of Science, CNKI and Wanfang were
      searched up to December 2016. Randomized controlled trials (RCTs) were eligible
      and the outcomes of muscle soreness, performance (including muscle maximal
      isometric force (MIF) and peak torque) and creatine kinase (CK) were used to
      assess the effectiveness of massage intervention on DOMS. Results: Eleven
      articles with a total of 23 data points (involving 504 participants) satisfied
      the inclusion criteria and were pooled in the meta-analysis. The findings
      demonstrated that muscle soreness rating decreased significantly when the
      participants received massage intervention compared with no intervention at 24 h
      (SMD: -0.61, 95% CI: -1.17 to -0.05, P = 0.03), 48 h (SMD: -1.51, 95% CI: -2.24
      to -0.77, P < 0.001), 72 h (SMD: -1.46, 95% CI: -2.59 to -0.33, P = 0.01) and in
      total (SMD: -1.16, 95% CI: -1.60 to -0.72, P < 0.001) after intense exercise.
      Additionally, massage therapy improved MIF (SMD: 0.56, 95% CI: 0.21-0.90, P =
      0.002) and peak torque (SMD: 0.38, 95% CI: 0.04-0.71, P = 0.03) as total effects.
      Furthermore, the serum CK level was reduced when participants received massage
      intervention (SMD: -0.64, 95% CI: -1.04 to -0.25, P = 0.001). Conclusion: The
      current evidence suggests that massage therapy after strenuous exercise could be
      effective for alleviating DOMS and improving muscle performance.

PMID- 29021763
TI  - The Functional Role of Individual-Alpha Based Frontal Asymmetry in the Evaluation
      of Emotional Pictures: Evidence from Event-Related Potentials.
AB  - The perceptual processing of emotional stimuli is subject to the regulation of
      brain function. This study investigated whether frontal electroencephalography
      (EEG) alpha asymmetry at resting conditions predicted the evaluation of emotional
      picture stimuli by event-related potentials (ERPs). In this study, participants
      first completed a 2-min resting task, and then passively viewed emotional
      pictures. The results showed that left active individuals had smaller frontal EEG
      alpha asymmetry scores to negative pictures than to positive and neutral
      pictures, whereas right active individuals had similar frontal EEG alpha
      asymmetry scores to negative, positive, and neutral pictures. Furthermore, the
      study showed a larger P300 to negative pictures than to positive and neutral
      pictures for left active individuals; however, there were no significant ERP
      differences to negative, positive, and neutral pictures for right active
      individuals. These findings suggest that frontal EEG alpha asymmetry at resting
      conditions can reflect interindividual differences in emotional perception
      tendencies to emotional picture stimuli.

PMID- 29021764
TI  - Multicomponent Intervention for Patients Admitted to an Emergency Unit for
      Suicide Attempt: An Exploratory Study.
AB  - Suicide is a major cause of premature deaths worldwide and belongs to the top
      priority public health issues. While suicide attempt is the most important risk
      factor for completed suicide, intervention for suicide attempters (SA) have
      produced mixed results. Since an important proportion of SA request medical care,
      emergency units (EU) are an opportune setting to implement such interventions.
      This exploratory study evaluated the feasibility and acceptability of a
      multicomponent intervention for SA admitted to an EU. The intervention consisted
      of coordination by a case manager of a joint crisis plan (JCP), an early meeting
      with relatives and the existing care network, as well as phone contacts during 3
      months after suicide attempt. Among 107 SA admitted to the emergency unit during
      the study period, 51 could not be included for logistical reason, 22 were
      excluded, and intervention was offered to 34. Of these, 15 refused the
      intervention, which was thus piloted with 19 SA. First-time attempters most
      frequently declined the intervention. Feasibility and acceptability of phone
      contacts and case manager were good, while JCPs and meetings were difficult to
      implement and perceived as less acceptable. Refusal pattern questions the global
      acceptability and is discussed: JCPs and meetings will have to be modified in
      order to improve their feasibility and acceptability, especially among first-time
      attempters.

PMID- 29021767
TI  - Editorial: Social Cognition, Motivation, and Interaction: How Do People Respond
      to Threats in Social Interactions?

PMID- 29021766
TI  - A Randomized Controlled Trial on Functional Relaxation as an Adjunct to
      Psychoeducation for Stress.
AB  - This randomized controlled trial investigated whether adding the
      psychodynamically based body-oriented psychotherapy "Functional Relaxation" (FR)
      to psychoeducation (PE) is more effective than PE alone to reduce stress and
      stress-associated complaints. Eighty-one participants with elevated stress
      levels, >=50 points on the global scale of the Perceived Stress Questionnaire
      (PSQ), received either 10 sessions of manualized FR + PE (n = 42) or two sessions
      of manualized PE alone (n = 39) in a group setting. Six FR trainers took part in
      this study. Stress-level (PSQ) was the primary outcome and secondary outcomes
      were depression (PHQ-9) and somatization (PHQ-15). Multilevel models for
      discontinuous change revealed that FR + PE was more helpful to reduce stress
      levels than PE from pre-treatment to post-treatment (t0 -> t1) as well as from
      pre-treatment to 6-month follow-up (t0 -> t2) (both p < 0.05) with effect sizes
      (d) being medium for PE (dt0 -> t1 = 0.57; dt0 -> t2 = 0.67) and large for FR +
      PE (dt0 -> t1 = 1.57; dt0 -> t2 = 1.39). Moreover, FR + PE affected depression
      and somatization more positively than did PE from t0 to t1 as well as from t0 to
      t2 (all p < 0.05). Effect sizes for depression were small to medium for PE (dt0 
      > t1 = 0.52; dt0 -> t2 = 0.37) and large for FR + PE (dt0 -> t1 = 1.04; dt0 -> t2
      = 0.95). Effect sizes for somatization were small for PE (dt0 -> t1 = 0.18; dt0 
      > t2 = 0.19) and medium to large for FR + PE (dt0 -> t1 = 0.73; dt0 -> t2 =
      0.93). In summary, the combination of FR and PE was more effective than PE alone.
      The results of the present trial provide first evidence of FR as a potent
      component of stress interventions. Adding FR to such interventions might better
      help prevent clinically relevant disorders such as depression or somatization.

PMID- 29021765
TI  - Enhancing Neuroplasticity to Augment Cognitive Remediation in Schizophrenia.
AB  - There is a burgeoning need for innovative treatment strategies to improve the
      cognitive deficits in schizophrenia. Cognitive remediation (CR) is effective at
      the group level, but the variability in treatment response is large. Given that
      CR may depend on intact neuroplasticity to produce cognitive gains, it is
      reasonable to combine it with strategies that harness patients' neuroplastic
      potential. In this review, we discuss two non-pharmacological approaches that can
      enhance neuroplasticity and possibly augment the effects of CR in schizophrenia:
      physical exercise and transcranial direct current stimulation (tDCS). Substantial
      body of evidence supports the beneficial effect of physical exercise on
      cognition, and a handful of studies in schizophrenia have shown that physical
      exercise in conjunction with CR has a larger impact on cognition than CR alone.
      Physical exercise is thought to stimulate neuroplasticity through the regulation
      of central growth factors, and current evidence points to brain-derived
      neurotrophic factor as the potential underlying mechanism through which physical
      exercise might enhance the effectiveness of CR. tDCS has emerged as a potential
      tool for cognitive enhancement and seems to affect the cellular mechanisms
      involved in long-term potentiation (LTP). A few reports have demonstrated the
      feasibility of integrating tDCS with CR in schizophrenia, but there are
      insufficient data to determine if this multimodal approach leads to incremental
      performance gain in patients. Larger randomized controlled trials are necessary
      to understand the mechanisms of the combined tDCS-CR intervention. Future
      research should take advantage of new developments in neuroplasticity paradigms
      to examine the effects of these interventions on LTP.

PMID- 29021768
TI  - Endogenous Oxytocin, Vasopressin, and Aggression in Domestic Dogs.
AB  - Aggressive behavior in dogs poses public health and animal welfare concerns,
      however the biological mechanisms regulating dog aggression are not well
      understood. We investigated the relationships between endogenous plasma oxytocin
      (OT) and vasopressin (AVP)-neuropeptides that have been linked to affiliative and
      aggressive behavior in other mammalian species-and aggression in domestic dogs.
      We first validated enzyme-linked immunosorbent assays (ELISAs) for the
      measurement of free (unbound) and total (free + bound) OT and AVP in dog plasma.
      In Experiment 1 we evaluated behavioral and neuroendocrine differences between a
      population of pet dogs with a history of chronic aggression toward conspecifics
      and a matched control group. Dogs with a history of aggression exhibited more
      aggressive behavior during simulated encounters with conspecifics, and had lower
      free, but higher total plasma AVP than matched controls, but there were no group
      differences for OT. In Experiment 2 we compared OT and AVP concentrations between
      pet dogs and a population of assistance dogs that have been bred for affiliative
      and non-aggressive temperaments, and investigated neuroendocrine predictors of
      individual differences in social behavior within the assistance dog population.
      Compared to pet dogs, assistance dogs had higher free and total OT, but there
      were no differences in either measure for AVP. Within the assistance dog
      population, dogs who behaved more aggressively toward a threatening stranger had
      higher total AVP than dogs who did not. Collectively these data suggest that
      endogenous OT and AVP may play critical roles in shaping dog social behavior,
      including aspects of both affiliation and aggression.

PMID- 29021770
TI  - The Differential Effects of Mindfulness and Distraction on Affect and Body
      Satisfaction Following Food Consumption.
AB  - This study investigated whether engaging in mindfulness following food
      consumption produced changes in affect and body satisfaction, as compared to a
      control distraction task. The moderating effects of eating pathology and
      neuroticism were also examined. A total of 110 female university students
      consumed food and water before engaging in either a mindfulness induction or a
      control distraction task. Participants completed trait measures of eating
      pathology and neuroticism at baseline, and measures of state affect and body
      satisfaction before and after food consumption, and after the induction. Results
      revealed that consuming food and water reduced positive affect. Unexpectedly,
      both the mindfulness group and distraction control group experienced similar
      improvements in negative affect and body satisfaction following the induction.
      Eating pathology and neuroticism did not moderate the observed changes. These
      findings suggest that both mindfulness and distraction may contribute to the
      effectiveness of treatments for disordered eating that incorporate both of these
      techniques, such as Dialectical Behavior Therapy.

PMID- 29021771
TI  - Age-Based Positivity Effects in Imagining and Recalling Future Positive and
      Negative Autobiographical Events.
AB  - Thoughts about the future reflect personal goals, and projections into the future
      enrich our emotional life. Researchers have taken an interest in determining
      whether the tendency to remember more positive than negative emotional events
      observed when recalling past events also appears when remembering imagined future
      events. The objective of this study was to examine the age-based positivity
      effect of recall for future positive and negative autobiographical events in
      young and older adults. Representative future events were first established to
      develop the cues used to prompt personal future events. In the production task,
      the participants were presented with eight positive and eight negative random
      future events of young or older adults as a model and the corresponding cues to
      generate their own positive and negative future autobiographical events. In the
      recall task, the participants recovered as many experiences as they could of the
      model and the positive and negative events produced by themselves. The
      participants correctly recalled more positive than negative events and committed
      more errors for negative than positive events, showing a clear tendency in both
      young and older adults to recall future imagined events as positive. Regarding
      age, the young adults recalled more events than the older participants whilst the
      older participants in particular showed better recall of their own imagined
      future events than the model's events, and committed more errors when recalling
      the model's events than their own imagined events. Regarding the positivity
      effect in incorrect recall, more than half of the errors were valence changes,
      most of these being from negative to positive events, and these valence changes
      were more pronounced in the older than in the younger adults. In general, there
      were fewer differences between young and older adults in the recall of positive
      events in comparison with negative events. Our findings suggest that people are
      well disposed toward recalling positive imagined future events and preserve a
      positive emotional state, suppressing negative memories.

PMID- 29021769
TI  - Interpersonal Coordination: Methods, Achievements, and Challenges.
AB  - Research regarding interpersonal coordination can be traced back to the early
      1960s when video recording began to be utilized in communication studies. Since
      then, technological advances have extended the range of techniques that can be
      used to accurately study interactional phenomena. Although such a diversity of
      methods contributes to the improvement of knowledge concerning interpersonal
      coordination, it has become increasingly difficult to maintain a comprehensive
      view of the field. In the present article, we review the main capture methods by
      describing their major findings, levels of description and limitations. We group
      them into three categories: video analysis, motion tracking, and
      psychophysiological and neurophysiological techniques. Revised evidence suggests
      that interpersonal coordination encompasses a family of morphological and
      temporal synchronies at different levels and that it is closely related to the
      construction and maintenance of a common social and affective space. We conclude
      by arguing that future research should address methodological challenges to
      advance the understanding of coordination phenomena.

PMID- 29021772
TI  - Incremental Theory of Intelligence Moderated the Relationship between Prior
      Achievement and School Engagement in Chinese High School Students.
AB  - School engagement plays a prominent role in promoting academic accomplishments.
      In contrast to the relative wealth of research that examined the impact of
      students' school engagement on their academic achievement, considerably less
      research has investigated the effect of high school students' prior achievement
      on their school engagement. The present study examined the relationship between
      prior achievement and school engagement among Chinese high school students. Based
      on the Dweck's social-cognitive theory of motivation, we further examined the
      moderating effect of students' theories of intelligence (TOIs) on this
      relationship. A total of 4036 (2066 girls) students from five public high school
      enrolled in grades 10 reported their high school entrance exam achievement in
      Chinese, Math and English, school engagement, and TOIs. Results showed that (a)
      students' prior achievement predicted their behavioral, emotional, and cognitive
      engagement, respectively, and (b) the association between prior achievement and
      behavioral, emotional, and cognitive engagement is strong for students with an
      incremental theory but not for those with an entity theory in the emotional and
      cognitive engagement. These findings suggest that prior achievement and
      incremental theory were implicated in relation to adolescents' school engagement.
      Implications and future research directions were discussed.

PMID- 29021773
TI  - The Grand Challenges for Evolutionary Psychology: Survival Challenges for a
      Discipline.

PMID- 29021775
TI  - Cardiac Findings in Amyotrophic Lateral Sclerosis: A Magnetic Resonance Imaging
      Study.
AB  - The objective of this study was to investigate the potential involvement of
      cardiac structure and function by cardiac magnetic resonance (CMR) imaging in
      amyotrophic lateral sclerosis (ALS) patients. Our study included 35 patients with
      ALS without a history of cardiac disease and an age- and gender-matched healthy
      control group (n = 34). All subjects received a CMR in a 1.5-T whole-body
      scanner. Patients were also screened with Holter monitoring, echocardiography,
      and a blood test of cardiac markers. Myocardial mass in ALS hearts was reduced
      compared to the control group, and ejection volumes in the left and right heart
      were severely decreased in ALS patients, as shown by echocardiography and CMR.
      The myocardium showed increased T1 enhancement in 77% of the patients compared to
      27% of controls (p = 0.0001). A trend toward late gadolinium enhancement patterns
      consistent with myocardial fibrosis was observed in 23.5% of the patients (9.1%
      of controls). Holter monitoring was normal in all patients as well as troponin T.
      Cardiac involvement seems to be present in ALS patients without clinical cardiac
      symptoms and with a normal cardiac routine assessment. Structural myocardial
      defects in CMR may be due to sympathetic dysfunction and may account for reported
      cardiac deaths in late-stage ALS patients.

PMID- 29021776
TI  - Sex Differences in rt-PA Utilization at Hospitals Treating Stroke: The National
      Inpatient Sample.
AB  - BACKGROUND AND PURPOSE: Sex and race disparities in recombinant tissue
      plasminogen activator (rt-PA) use have been reported. We sought to explore sex
      and race differences in the utilization of rt-PA at primary stroke centers (PSCs)
      compared to non-PSCs across the US. METHODS: Data from the National (Nationwide)
      Inpatient Sample (NIS) 2004-2010 was utilized to assess sex differences in
      treatment for ischemic stroke in PSCs compared to non-PSCs. RESULTS: There were
      304,152 hospitalizations with a primary diagnosis of ischemic stroke between 2004
      and 2010 in the analysis: 75,160 (24.7%) patients were evaluated at a PSC. A
      little over half of the patients evaluated at PSCs were female (53.8%). A lower
      proportion of women than men received rt-PA at both PSCs (6.8 vs. 7.5%, p <
      0.001) and non-PSCs (2.3 vs. 2.8%, p < 0.001). After adjustment for potential
      confounders the odds of being treated with rt-PA remained lower for women
      regardless of presentation to a PSC (OR 0.87, 95% CI 0.81-0.94) or non-PSC (OR
      0.88, 95% CI 0.82-0.94). After stratifying by sex and race, the lowest absolute
      treatment rates were observed in black women (4.4% at PSC, 1.9% at non-PSC). The
      odds of treatment, relative to white men, was however lowest for white women (PSC
      OR = 0.85, 95% CI 0.78-0.93; non-PSC OR = 0.80, 95% CI 0.75-0.85). In the
      multivariable model, sex did not modify the effect of PSC certification on rt-PA
      utilization (p-value for interaction = 0.58). CONCLUSION: Women are less likely
      to receive rt-PA than men at both PSCs and non-PSCs. Absolute treatment rates are
      lowest in black women, although the relative difference in men and women was
      greatest for white women.

PMID- 29021774
TI  - Corrigendum: Marital Satisfaction, Sex, Age, Marriage Duration, Religion, Number
      of Children, Economic Status, Education, and Collectivistic Values: Data from 33
      Countries.
AB  - [This corrects the article on p. 1199 in vol. 8, PMID: 28785230.].

PMID- 29021777
TI  - Circulating Cholesterol Levels May Link to the Factors Influencing Parkinson's
      Risk.
AB  - OBJECTIVES: A growing literature suggests that circulating cholesterol levels
      have been associated with Parkinson's disease (PD). In this study, we
      investigated a possible causal basis for the cholesterol-PD link. METHODS:
      Fasting plasma cholesterol levels were obtained from 91 PD and 70 age- and gender
      matched controls from an NINDS PD Biomarkers Program cohort at the Pennsylvania
      State University College of Medicine. Based on the literature, genetic
      polymorphisms in selected cholesterol management genes (APOE, LDLR, LRP1, and
      LRPAP1) were chosen as confounding variables because they may influence both
      cholesterol levels and PD risk. First, the marginal structure model was applied,
      where the associations of total- and LDL-cholesterol levels with genetic
      polymorphisms, statin usage, and smoking history were estimated using linear
      regression. Then, potential causal influences of total- and LDL-cholesterol on PD
      occurrence were investigated using a generalized propensity score approach in the
      second step. RESULTS: Both statins (p < 0.001) and LRP1 (p < 0.03) influenced
      total- and LDL-cholesterol levels. There also was a trend for APOE to affect
      total- and LDL-cholesterol (p = 0.08 for both), and for LRPAR1 to affect LDL
      cholesterol (p = 0.05). Conversely, LDLR did not influence plasma cholesterol
      levels (p > 0.19). Based on propensity score methods, lower total- and LDL
      cholesterol were significantly linked to PD (p < 0.001 and p = 0.04,
      respectively). CONCLUSION: The current study suggests that circulating total- and
      LDL-cholesterol levels potentially may be linked to the factor(s) influencing PD
      risk. Further studies to validate these results would impact our understanding of
      the role of cholesterol as a risk factor in PD, and its relationship to recent
      public health controversies.

PMID- 29021778
TI  - The Combined Quantification and Interpretation of Multiple Quantitative Magnetic
      Resonance Imaging Metrics Enlightens Longitudinal Changes Compatible with Brain
      Repair in Relapsing-Remitting Multiple Sclerosis Patients.
AB  - OBJECTIVE: Quantitative and semi-quantitative MRI (qMRI) metrics provide
      complementary specificity and differential sensitivity to pathological brain
      changes compatible with brain inflammation, degeneration, and repair. Moreover,
      advanced magnetic resonance imaging (MRI) metrics with overlapping elements
      amplify the true tissue-related information and limit measurement noise. In this
      work, we combined multiple advanced MRI parameters to assess focal and diffuse
      brain changes over 2 years in a group of early-stage relapsing-remitting MS
      patients. METHODS: Thirty relapsing-remitting MS patients with less than 5 years
      disease duration and nine healthy subjects underwent 3T MRI at baseline and after
      2 years including T1, T2, T2* relaxometry, and magnetization transfer imaging. To
      assess longitudinal changes in normal-appearing (NA) tissue and lesions, we used
      analyses of variance and Bonferroni correction for multiple comparisons.
      Multivariate linear regression was used to assess the correlation between
      clinical outcome and multiparametric MRI changes in lesions and NA tissue.
      RESULTS: In patients, we measured a significant longitudinal decrease of mean T2
      relaxation times in NA white matter (p = 0.005) and a decrease of T1 relaxation
      times in the pallidum (p < 0.05), which are compatible with edema reabsorption
      and/or iron deposition. No longitudinal changes in qMRI metrics were observed in
      controls. In MS lesions, we measured a decrease in T1 relaxation time (p-value <
      2.2e-16) and a significant increase in MTR (p-value < 1e-6), suggesting repair
      mechanisms, such as remyelination, increased axonal density, and/or a gliosis.
      Last, the evolution of advanced MRI metrics-and not changes in lesions or brain
      volume-were correlated to motor and cognitive tests scores evolution (Adj-R2 >
      0.4, p < 0.05). In summary, the combination of multiple advanced MRI provided
      evidence of changes compatible with focal and diffuse brain repair at early MS
      stages as suggested by histopathological studies.

PMID- 29021779
TI  - Xenon Reduces Neuronal Hippocampal Damage and Alters the Pattern of Microglial
      Activation after Experimental Subarachnoid Hemorrhage: A Randomized Controlled
      Animal Trial.
AB  - OBJECTIVE: The neuroprotective properties of the noble gas xenon have already
      been demonstrated using a variety of injury models. Here, we examine for the
      first time xenon's possible effect in attenuating early brain injury (EBI) and
      its influence on posthemorrhagic microglial neuroinflammation in an in vivo rat
      model of subarachnoid hemorrhage (SAH). METHODS: Sprague-Dawley rats (n = 22)
      were randomly assigned to receive either Sham surgery (n = 9; divided into two
      groups) or SAH induction via endovascular perforation (n = 13, divided into two
      groups). Of those randomized for SAH, 7 animals were postoperatively ventilated
      with 50 vol% oxygen/50 vol% xenon for 1 h and 6 received 50 vol% oxygen/50 vol%
      nitrogen (control). The animals were sacrificed 24 h after SAH. Of each animal, a
      cerebral coronal section (-3.60 mm from bregma) was selected for assessment of
      histological damage 24 h after SAH. A 5-point neurohistopathological severity
      score was applied to assess neuronal cell damage in H&E and NeuN stained sections
      in a total of four predefined anatomical regions of interest. Microglial
      activation was evaluated by a software-assisted cell count of Iba-1 stained
      slices in three cortical regions of interest. RESULTS: A diffuse cellular damage
      was apparent in all regions of the ipsilateral hippocampus 24 h after SAH. Xenon
      treated animals presented with a milder damage after SAH. This effect was found
      to be particularly pronounced in the medial regions of the hippocampus, CA3 (p =
      0.040), and dentate gyrus (DG p = 0.040). However, for the CA1 and CA2 regions,
      there were no statistical differences in neuronal damage according to our
      histological scoring. A cell count of activated microglia was lower in the cortex
      of xenon-treated animals. This difference was especially apparent in the left
      piriform cortex (p = 0.017). CONCLUSION: In animals treated with 50 vol% xenon
      (for 1 h) after SAH, a less pronounced neuronal damage was observed for the
      ipsilateral hippocampal regions CA3 and DG, when compared to the control group.
      In xenon-treated animals, a lower microglial cell count was observed suggesting
      an immunomodulatory effect generated by xenon. As for now, these results cannot
      be generalized as only some hippocampal regions are affected. Future studies
      should assess the time and localization dependency of xenon's beneficial
      properties after SAH.

PMID- 29021780
TI  - Chronic 5-Aminoimidazole-4-Carboxamide-1-beta-d-Ribofuranoside Treatment Induces
      Phenotypic Changes in Skeletal Muscle, but Does Not Improve Disease Outcomes in
      the R6/2 Mouse Model of Huntington's Disease.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative genetic
      disorder characterized by motor, cognitive, and psychiatric symptoms. It is well
      established that regular physical activity supports brain health, benefiting
      cognitive function, mental health as well as brain structure and plasticity.
      Exercise mimetics (EMs) are a group of drugs and small molecules that target
      signaling pathways in skeletal muscle known to be activated by endurance
      exercise. The EM 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR)
      has been shown to induce cognitive benefits in healthy mice. Since AICAR does not
      readily cross the blood-brain barrier, its beneficial effect on the brain has
      been ascribed to its impact on skeletal muscle. Our objective, therefore, was to
      examine the effect of chronic AICAR treatment on the muscular and neurological
      pathology in a mouse model of HD. To this end, R6/2 mice were treated with AICAR
      for 8 weeks and underwent regular neurobehavioral testing. Under our conditions,
      AICAR increased expression of PGC-1alpha, a powerful phenotypic modifier of
      muscle, and induced the expected shift toward a more oxidative muscle phenotype
      in R6/2 mice. However, this treatment failed to induce benefits on HD
      progression. Indeed, neurobehavioral deficits, striatal, and muscle mutant
      huntingtin aggregate density, as well as muscle atrophy were not mitigated by the
      chronic administration of AICAR. Although the muscle adaptations seen in HD mice
      following AICAR treatment may still provide therapeutically relevant benefits to
      patients with limited mobility, our findings indicate that under our experimental
      conditions, AICAR had no effect on several hallmarks of HD.

PMID- 29021782
TI  - Functional Diversity of Fungal Communities in Soil Contaminated with Diesel Oil.
AB  - The widespread use and consumption of crude oil draws the public's attention to
      the fate of petroleum hydrocarbons in the environment, as they can permeate the
      soil environment in an uncontrollable manner. Contamination of soils with
      petroleum products, including diesel oil (DO), can cause changes in the
      microbiological soil properties. The effect of diesel oil on the functional
      diversity of fungi was tested in a model experiment during 270 days. Fungi were
      isolated from soil and identified. The functional diversity of fungal communities
      was also determined. Fungi were identified with the MALDI-TOF method, while the
      functional diversity was determined using FF-plates made by Biolog(r), with 95
      carbon sources. Moreover, the diesel oil degradation dynamics was assessed. The
      research showed that soil contaminated with diesel oil is characterized by a
      higher activity of oxireductases and a higher number of fungi than soil not
      exposed to the pressure of this product. The DO pollution has an adverse effect
      on the diversity of fungal community. This is proved by significantly lower
      values of the Average Well-Color Development, substrates Richness (R) and Shannon
      Weaver (H) indices at day 270 after contamination. The consequences of DO
      affecting soil not submitted to remediation are persistent. After 270 days, only
      64% of four-ringed, 28% of five-ringed, 21% of 2-3-ringed and 16% of six-ringed
      PAHs underwent degradation. The lasting effect of DO on communities of fungi led
      to a decrease in their functional diversity. The assessment of the response of
      fungi to DO pollution made on the basis of the development of colonies on Petri
      dishes [Colony Development (CD) and Eco-physiological Diversity (EP) indices] is
      consistent with the analysis based on the FF MicroPlate system by Biolog(r).
      Thus, a combination of the FF MicroPlate system by Biolog(r) with the
      simultaneous calculation of CD and EP indices alongside the concurrent
      determination of the content of PAHs and activity of oxireductases provides an
      opportunity to achieve relatively complete characterization of the consequences
      of a long-term impact of diesel oil on soil fungi.

PMID- 29021783
TI  - Extracellular Polymeric Substance Production and Aggregated Bacteria Colonization
      Influence the Competition of Microbes in Biofilms.
AB  - The production of extracellular polymeric substance (EPS) is important for the
      survival of biofilms. However, EPS production is costly for bacteria and the
      bacterial strains that produce EPS (EPS+) grow in the same environment as non
      producers (EPS-) leading to competition between these strains for nutrients and
      space. The outcome of this competition is likely to be dependent on factors such
      as initial attachment, EPS production rate, ambient nutrient levels and quorum
      sensing. We use an Individual-based Model (IbM) to study the competition between
      EPS+ and EPS- strains by varying the nature of initial colonizers which can
      either be in the form of single cells or multicellular aggregates. The microbes
      with EPS+ characteristics obtain a competitive advantage if they initially
      colonize the surface as smaller aggregates and are widely spread-out between the
      cells of EPS-, when both are deposited on the substratum. Furthermore, the
      results show that quorum sensing-regulated EPS production may significantly
      reduce the fitness of EPS producers when they initially deposit as aggregates.
      The results provide insights into how the distribution of bacterial aggregates
      during initial colonization could be a deciding factor in the competition among
      different strains in biofilms.

PMID- 29021784
TI  - Synthetic Peptides to Target Stringent Response-Controlled Virulence in a
      Pseudomonas aeruginosa Murine Cutaneous Infection Model.
AB  - Microorganisms continuously monitor their surroundings and adaptively respond to
      environmental cues. One way to cope with various stress-related situations is
      through the activation of the stringent stress response pathway. In Pseudomonas
      aeruginosa this pathway is controlled and coordinated by the activity of the RelA
      and SpoT enzymes that metabolize the small nucleotide secondary messenger
      molecule (p)ppGpp. Intracellular ppGpp concentrations are crucial in mediating
      adaptive responses and virulence. Targeting this cellular stress response has
      recently been the focus of an alternative approach to fight antibiotic resistant
      bacteria. Here, we examined the role of the stringent response in the virulence
      of P. aeruginosa PAO1 and the Liverpool epidemic strain LESB58. A
      DeltarelA/DeltaspoT double mutant showed decreased cytotoxicity toward human
      epithelial cells, exhibited reduced hemolytic activity, and caused down
      regulation of the expression of the alkaline protease aprA gene in stringent
      response mutants grown on blood agar plates. Promoter fusions of relA or spoT to
      a bioluminescence reporter gene revealed that both genes were expressed during
      the formation of cutaneous abscesses in mice. Intriguingly, virulence was
      attenuated in vivo by the DeltarelA/DeltaspoT double mutant, but not the relA
      mutant nor the DeltarelA/DeltaspoT complemented with either gene. Treatment of a
      cutaneous P. aeruginosa PAO1 infection with anti-biofilm peptides increased
      animal welfare, decreased dermonecrotic lesion sizes, and reduced bacterial
      numbers recovered from abscesses, resembling the phenotype of the
      DeltarelA/DeltaspoT infection. It was previously demonstrated by our lab that
      ppGpp could be targeted by synthetic peptides; here we demonstrated that spoT
      promoter activity was suppressed during cutaneous abscess formation by treatment
      with peptides DJK-5 and 1018, and that a peptide-treated relA complemented
      stringent response double mutant strain exhibited reduced peptide susceptibility.
      Overall these data strongly indicated that synthetic peptides target the P.
      aeruginosa stringent response in vivo and thus offer a promising novel
      therapeutic approach.

PMID- 29021785
TI  - Amino Acid Sensor Kinase Gcn2 Is Required for Conidiation, Secondary Metabolism,
      and Cell Wall Integrity in the Taxol-Producer Pestalotiopsis microspora.
AB  - The canonical Gcn2/Cpc1 kinase in fungi coordinates the expression of target
      genes in response to amino acid starvation. To investigate its possible role in
      secondary metabolism, we characterized a gcn2 homolog in the taxol-producing
      fungus Pestalotiopsis microspora. Deletion of the gene led to severe
      physiological defects under amino acid starvation, suggesting a conserved
      function of gcn2 in amino acid sensing. The mutant strain Deltagcn2 displayed
      retardation in vegetative growth. It generated dramatically fewer conidia,
      suggesting a connection between amino acid metabolism and conidiation in this
      fungus. Importantly, disruption of the gene altered the production of secondary
      metabolites by HPLC profiling. For instance, under amino acid starvation, the
      deletion strain Deltagcn2 barely produced secondary metabolites including the
      known natural product pestalotiollide B. Even more, we showed that gcn2 played
      critical roles in the tolerance to several stress conditions. Deltagcn2 exhibited
      a hypersensitivity to Calcofluor white and Congo red, implying a role of Gcn2 in
      maintaining the integrity of the cell wall. This study suggests that Gcn2 kinase
      is an important global regulator in the growth and development of filamentous
      fungi and will provide knowledge for the manipulation of secondary metabolism in
      P. microspora.

PMID- 29021781
TI  - Cross Talk between Adipose Tissue and Placenta in Obese and Gestational Diabetes
      Mellitus Pregnancies via Exosomes.
AB  - Obesity is an important public health issue worldwide, where it is commonly
      associated with the development of metabolic disorders, especially insulin
      resistance (IR). Maternal obesity is associated with an increased risk of
      pregnancy complications, especially gestational diabetes mellitus (GDM).
      Metabolism is a vital process for energy production and the maintenance of
      essential cellular functions. Excess energy storage is predominantly regulated by
      the adipose tissue. Primarily made up of adipocytes, adipose tissue acts as the
      body's major energy reservoir. The role of adipose tissue, however, is not
      restricted to a "bag of fat." The adipose tissue is an endocrine organ, secreting
      various adipokines, enzymes, growth factors, and hormones that take part in
      glucose and lipid metabolism. In obesity, the greater portion of the adipose
      tissue comprises fat, and there is increased pro-inflammatory cytokine secretion,
      macrophage infiltration, and reduced insulin sensitivity. Obesity contributes to
      systemic IR and its associated metabolic complications. Similar to adipose
      tissue, the placenta is also an endocrine organ. During pregnancy, the placenta
      secretes various molecules to maintain pregnancy physiology. In addition, the
      placenta plays an important role in metabolism and exchange of nutrients between
      mother and fetus. Inflammation at the placenta may contribute to the severity of
      maternal IR and her likelihood of developing GDM and may also mediate the adverse
      consequences of obesity and GDM on the fetus. Interestingly, studies on maternal
      insulin sensitivity and secretion of placental hormones have not shown a positive
      correlation between these phenomena. Recently, a great interest in the field of
      extracellular vesicles (EVs) has been observed in the literature. EVs are
      produced by a wide range of cells and are present in all biological fluids. EVs
      are involved in cell-to-cell communication. Recent evidence points to an
      association between adipose tissue-derived EVs and metabolic syndrome in obesity.
      In this review, we will discuss the changes in human placenta and adipose tissue
      in GDM and obesity and summarize the findings regarding the role of adipose
      tissue and placenta-derived EVs, with an emphasis on exosomes in obesity, and the
      contribution of obesity to the development of GDM.

PMID- 29021786
TI  - A New Role for Helicobacter pylori Urease: Contributions to Angiogenesis.
AB  - Helicobacter pylori is a pathogen involved in gastric diseases such as ulcers and
      carcinomas. H. pylori's urease is an important virulence factor produced in large
      amounts by this bacterium. In previous studies, we have shown that this protein
      is able to activate several cell types like neutrophils, monocytes, platelets,
      endothelial cells, and gastric epithelial cells. Angiogenesis is a physiological
      process implicated in growth, invasion and metastization of tumors. Here, we have
      analyzed the angiogenic potential of H. pylori urease (HPU) in gastric epithelial
      cells. No cytotoxicity was observed in AGS, Kato-III, and MKN28 gastric cell
      lines treated with 300 nM HPU, as evaluated by the 3-(4,5-Dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT) assay. As we previously reported in
      neutrophils, treatment with 300 nM HPU also had an anti-apoptotic effect in
      gastric epithelial cells leading to a 2.2-fold increase in the levels of Bcl-XL
      after 6 h, and a decrease of 80% in the content of BAD, after 48 h, two
      mitochondrial proteins involved in regulation of apoptosis. Within 10 min of
      exposure, HPU is rapidly internalized by gastric epithelial cells. Treatment of
      the gastric cells with methyl-beta-cyclodextrin abolished HPU internalization
      suggesting a cholesterol-dependent process. HPU induces the expression of pro
      angiogenic factors and the decrease of expression of anti-angiogenic factors by
      AGS cells. The angiogenic activity of HPU was analyzed using in vitro and in vivo
      models. HPU induced formation of tube-like structures by human umbilical vascular
      endothelial cells in a 9 h experiment. In the chicken embryo chorioallantoic
      membrane model, HPU induced intense neo-vascularization after 3 days. In
      conclusion, our results indicate that besides allowing bacterial colonization of
      the gastric mucosa, H. pylori's urease triggers processes that initiate pro
      angiogenic responses in different cellular models. Thus, this bacterial urease, a
      major virulence factor, may also play a role in gastric carcinoma development.

PMID- 29021787
TI  - Integron Digestive Carriage in Human and Cattle: A "One Health" Cultivation
      Independent Approach.
AB  - Objectives: Dissemination of antimicrobial resistance (AMR) is a global issue
      that requires the adoption of a "One-Health" approach promoting integration of
      human and animal health. Besides culture-dependent techniques frequently used for
      AMR surveillance, cultivation-independent methods can give additional insights
      into the diversity and reservoir of AMR genetic determinants. Integrons are
      molecular markers that can provide overall and reliable estimation of AMR
      dissemination. In this study, considering the "One-Health" approach, we have
      analyzed the integron digestive carriage from stools of humans and cattle living
      in a same area and exposed to different antibiotic selection pressures. Methods:
      Three collections of human [general population (GP) and intensive care unit
      patients (ICUs)] and bovine (BOV) stool samples were analyzed. The three main
      classes of integrons were detected using a multiplex qPCR both from total DNA
      extracted from stools, and from Gram-negative bacteria obtained by culture after
      an enrichment step. Results: With the cultivation-independent approach, integron
      carriage was 43.8, 52.7, and 65.6% for GP, ICU, and BOV respectively, percentages
      being at least twofold higher to those obtained with the cultivation-dependent
      approach. Class 1 integrons were the most prevalent; class 2 integrons seemed
      more associated to cattle than to humans; no class 3 integron was detected. The
      integron carriage was not significantly different between GP and ICU populations
      according to the antibiotic consumption, whatever the approach. Conclusion: The
      cultivation-independent approach constitutes a complementary exploratory method
      to investigate the integron digestive carriage of humans and bovines, notably
      within subjects under antibiotic treatment. The high frequency of carriage of
      integrons in the gut is of clinical significance, integrons being able to easily
      acquire and exchange resistant genes under antibiotic selective pressure and so
      leading to the dissemination of resistant bacteria.

PMID- 29021788
TI  - MicroRNAs-Based Inter-Domain Communication between the Host and Members of the
      Gut Microbiome.
AB  - The gut microbiome is an important modulator of host gene expression, impacting
      important functions such as the innate immune response. Recent evidence suggests
      that the inter-domain communication between the gut microbiome and host may in
      part occur via microRNAs (small, non-coding RNA molecules) which are often
      differentially expressed in the presence of bacteria and can even be released and
      taken up by bacteria. The role of microRNAs in microbiome-host communication in
      intestinal diseases is not fully understood, particularly in diseases impacted by
      exposure to environmental toxicants. Here, we review the present knowledge in the
      areas of microbiome and microRNA expression-based communication, microbiome and
      intestinal disease relationships, and microRNA expression responses to intestinal
      diseases. We also examine potential links between host microRNA-microbiota
      communication and exposure to environmental toxicants by reviewing connections
      between (i) toxicants and microRNA expression, (ii) toxicants and gut diseases,
      and (iii) toxicants and the gut microbiome. Future multidisciplinary research in
      this area is needed to uncover these interactions with the potential to impact
      how gut-microbiome associated diseases [e.g., inflammatory bowel disease (IBD)
      and many others] are managed.

PMID- 29021789
TI  - The Endophytic Symbiont-Pseudomonas aeruginosa Stimulates the Antioxidant
      Activity and Growth of Achyranthes aspera L.
AB  - A plant growth promoting bacterial endophyte designated as AL2-14B isolated from
      the leaves of Achyranthes aspera L. was identified as Pseudomonas aeruginosa
      based on its phenotypic and physiological features, and 16S rRNA gene sequence
      analysis. AL2-14B had plant growth stimulating attributes including siderophore
      and indole acetic acid release, inorganic phosphate solubilization, along with
      nitrogenase, ammonification, and protease activities. It also exhibited
      antifungal property against Rhizoctonia solani. The plantlets grown in germ-free
      condition were inoculated with AL2-14B and studied for the colonization of
      endophyte. Significant increase in population of AL2-14B between 3rd and 5th days
      after inoculation was recorded. The treatment of plants with endophytic P.
      aeruginosa AL2-14B increased nitrogen, phosphorus, potassium (NPK) contents in
      plant by 3.8, 12.59, and 19.15%, respectively. Significant enhancement of shoot
      and root length, dry leaf, dry shoot and dry root weight, and leaf surface area
      as compared to control (P < 0.05) was recorded in AL2-14B inoculated plants. The
      antioxidant activities increased in plants grown in germ-free conditions and
      inoculated with AL2-14B. The present study emphasizes on the role of diazotrophic
      endophyte P. aeruginosa AL2-14B in stimulating growth of A. aspera L. and
      improvement of its medicinal properties. Significant increase in growth and
      antioxidant content of P. aeruginosa AL2-14B treated plants suggests the
      possibility of an economical and eco-friendly mean of achieving antioxidants
      rich, healthier A. aspera plants.

PMID- 29021790
TI  - Ammonia Oxidation and Nitrite Reduction in the Verrucomicrobial Methanotroph
      Methylacidiphilum fumariolicum SolV.
AB  - The Solfatara volcano near Naples (Italy), the origin of the recently discovered
      verrucomicrobial methanotroph Methylacidiphilum fumariolicum SolV was shown to
      contain ammonium ([Formula: see text]) at concentrations ranging from 1 to 28 mM.
      Ammonia (NH3) can be converted to toxic hydroxylamine (NH2OH) by the particulate
      methane monooxygenase (pMMO), the first enzyme of the methane (CH4) oxidation
      pathway. Methanotrophs rapidly detoxify the intermediate NH2OH. Here, we show
      that strain SolV performs ammonium oxidation to nitrite at a rate of 48.2 nmol
      [Formula: see text].h-1.mg DW-1 under O2 limitation in a continuous culture grown
      on hydrogen (H2) as an electron donor. In addition, strain SolV carries out
      nitrite reduction at a rate of 74.4 nmol [Formula: see text].h-1.mg DW-1 under
      anoxic condition at pH 5-6. This range of pH was selected to minimize the
      chemical conversion of nitrite ([Formula: see text]) potentially occurring at
      more acidic pH values. Furthermore, at pH 6, we showed that the affinity
      constants (K s ) of the cells for NH3 vary from 5 to 270 MUM in the batch
      incubations with 0.5-8% (v/v) CH4, respectively. Detailed kinetic analysis showed
      competitive substrate inhibition between CH4 and NH3. Using transcriptome
      analysis, we showed up-regulation of the gene encoding hydroxylamine
      dehydrogenase (haoA) cells grown on H2/[Formula: see text] compared to the cells
      grown on CH4/[Formula: see text] which do not have to cope with reactive N
      compounds. The denitrifying genes nirk and norC showed high expression in
      H2/[Formula: see text] and CH4/[Formula: see text] grown cells compared to cells
      growing at MUmax (with no limitation) while the norB gene showed downregulation
      in CH4/[Formula: see text] grown cells. These cells showed a strong upregulation
      of the genes in nitrate/nitrite assimilation. Our results demonstrate that strain
      SolV can perform ammonium oxidation producing nitrite. At high concentrations of
      ammonium this may results in toxic effects. However, at low oxygen concentrations
      strain SolV is able to reduce nitrite to N2O to cope with this toxicity.

PMID- 29021792
TI  - Corrigendum: Cross-Talk between Staphylococcus aureus and Other Staphylococcal
      Species via the agr Quorum Sensing System.
AB  - [This corrects the article on p. 1733 in vol. 7, PMID: 27877157.].

PMID- 29021791
TI  - Cofactor Tail Length Modulates Catalysis of Bacterial F420-Dependent
      Oxidoreductases.
AB  - F420 is a microbial cofactor that mediates a wide range of physiologically
      important and industrially relevant redox reactions, including in methanogenesis
      and tetracycline biosynthesis. This deazaflavin comprises a redox-active
      isoalloxazine headgroup conjugated to a lactyloligoglutamyl tail. Here we studied
      the catalytic significance of the oligoglutamate chain, which differs in length
      between bacteria and archaea. We purified short-chain F420 (two glutamates) from
      a methanogen isolate and long-chain F420 (five to eight glutamates) from a
      recombinant mycobacterium, confirming their different chain lengths by HPLC and
      LC/MS analysis. F420 purified from both sources was catalytically compatible with
      purified enzymes from the three major bacterial families of F420-dependent
      oxidoreductases. However, long-chain F420 bound to these enzymes with a six- to
      ten-fold higher affinity than short-chain F420. The cofactor side chain also
      significantly modulated the kinetics of the enzymes, with long-chain F420
      increasing the substrate affinity (lower Km) but reducing the turnover rate
      (lower kcat) of the enzymes. Molecular dynamics simulations and comparative
      structural analysis suggest that the oligoglutamate chain of F420 makes dynamic
      electrostatic interactions with conserved surface residues of the oxidoreductases
      while the headgroup binds the catalytic site. In conjunction with the kinetic
      data, this suggests that electrostatic interactions made by the oligoglutamate
      tail result in higher-affinity, lower-turnover catalysis. Physiologically, we
      propose that bacteria have selected for long-chain F420 to better control
      cellular redox reactions despite tradeoffs in catalytic rate. Conversely, this
      suggests that industrial use of shorter-length F420 will greatly increase the
      rates of bioremediation and biocatalysis processes relying on purified F420
      dependent oxidoreductases.

PMID- 29021793
TI  - Intracellular Crosslinking of Filoviral Nucleoproteins with Xintrabodies
      Restricts Viral Packaging.
AB  - Viruses assemble large macromolecular repeat structures that become part of the
      infectious particles or virions. Ribonucleocapsids (RNCs) of negative strand RNA
      viruses are a prime example where repetition of nucleoprotein (NP) along the
      genome creates a core polymeric helical scaffold that accommodates other
      nucleocapsid proteins including viral polymerase. The RNCs are transported
      through the cytosol for packaging into virions through association with viral
      matrix proteins at cell membranes. We hypothesized that RNC would be ideal
      targets for crosslinkers engineered to promote aberrant protein-protein
      interactions, thereby blocking their orderly transport and packaging. Previously,
      we had generated single-domain antibodies (sdAbs) against Filoviruses that have
      all targeted highly conserved C-terminal regions of NP known to be repetitively
      exposed along the length of the RNCs of Marburgvirus (MARV) and Ebolavirus
      (EBOV). Our crosslinker design consisted of dimeric sdAb expressed
      intracellularly, which we call Xintrabodies (X- for crosslinking). Electron
      microscopy of purified NP polymers incubated with purified sdAb constructs showed
      NP aggregation occurred in a genus-specific manner with dimeric and not monomeric
      sdAb. A virus-like particle (VLP) assay was used for initial evaluation where we
      found that dimeric sdAb inhibited NP incorporation into VP40-based VLPs whereas
      monomeric sdAb did not. Inhibition of NP packaging was genus specific. Confocal
      microscopy revealed dimeric sdAb was diffuse when expressed alone but focused on
      pools of NP when the two were coexpressed, while monomeric sdAb showed ambivalent
      partition. Infection of stable Vero cell lines expressing dimeric sdAb specific
      for either MARV or EBOV NP resulted in smaller plaques and reduced progeny of
      cognate virus relative to wild-type Vero cells. Though the impact was marginal at
      later time-points, the collective data suggest that viral replication can be
      reduced by crosslinking intracellular NP using relatively small amounts of
      dimeric sdAb to restrict NP packaging. The stoichiometry and ease of application
      of the approach would likely benefit from transitioning away from intracellular
      expression of crosslinking sdAb to exogenous delivery of antibody. By retuning
      sdAb specificity, the approach of crosslinking highly conserved regions of
      assembly critical proteins may well be applicable to inhibiting replication
      processes of a broad spectrum of viruses.

PMID- 29021795
TI  - Neuroendocrine and Immune Responses Undertake Different Fates following
      Tryptophan or Methionine Dietary Treatment: Tales from a Teleost Model.
AB  - Methionine and tryptophan appear to be fundamental in specific cellular pathways
      involved in the immune response mechanisms, including stimulation of T-regulatory
      cells by tryptophan metabolites or pro-inflammatory effects upon methionine
      supplementation. Thus, the aim of this study was to evaluate the immunomodulatory
      effect of these amino acids on the inflammatory and neuroendocrine responses in
      juveniles of European seabass, Dicentrarchus labrax. To achieve this, goal fish
      were fed for 14 days methionine and tryptophan-supplemented diets (MET and TRP,
      respectively, 2* dietary requirement level) or a control diet meeting the amino
      acids requirement levels (CTRL). Fish were sampled for immune status assessment
      and the remaining fish were challenged with intraperitoneally injected
      inactivated Photobacterium damselae subsp. piscicida and sampled either 4 or 24 h
      post-injection. Respiratory burst activity, brain monoamines, plasma cortisol,
      and immune-related gene expression showed distinct and sometimes opposite
      patterns regarding the effects of dietary amino acids. While neuroendocrine
      intermediates were not affected by any dietary treatment at the end of the
      feeding trial, both supplemented diets led to increased levels of plasma cortisol
      after the inflammatory insult, while brain monoamine content was higher in TRP
      fed fish. Peripheral blood respiratory burst was higher in TRP-fed fish injected
      with the bacteria inoculum but only compared to those fed MET. However, no
      changes were detected in total antioxidant capacity. Complement factor 3 was
      upregulated in MET-fed fish but methionine seemed to poorly affect other genes
      expression patterns. In contrast, fish fed MET showed increased immune cells
      numbers both before and after immune challenge, suggesting a strong enhancing
      effect of methionine on immune cells proliferation. Differently, tryptophan
      effects on inflammatory transcripts suggested an inhibitory mode of action. This,
      together with a high production of brain monoamine and cortisol levels, suggests
      that tryptophan might mediate regulatory mechanisms of neuroendocrine and immune
      systems cooperation. Overall, more studies are needed to ascertain the role of
      methionine and tryptophan in modulating (stimulate or regulate) fish immune and
      neuroendocrine responses.

PMID- 29021794
TI  - CD95/Fas, Non-Apoptotic Signaling Pathways, and Kinases.
AB  - Endothelial cells lining new blood vessels that develop during inflammatory
      disorders or cancers act as doors that either allow or block access to the tumor
      or inflamed organ. Recent data show that these endothelial cells in cancer
      tissues and inflamed tissues of lupus patients overexpress CD95L, the biological
      role of which is a subject of debate. The receptor CD95 (also named Fas or
      apoptosis antigen 1) belongs to the tumor necrosis factor (TNF) receptor
      superfamily. Its cognate ligand, CD95L, is implicated in immune homeostasis and
      immune surveillance. Because mutations of this receptor or its ligand lead to
      autoimmune disorders such as systemic lupus erythematosus (SLE) and cancers, CD95
      and CD95L were initially thought to play a role in immune homeostasis and tumor
      elimination via apoptotic signaling pathways. However, recent data reveal that
      CD95 also evokes non-apoptotic signals, promotes inflammation, and contributes to
      carcinogenesis; therefore, it is difficult to dissect its apoptotic effects from
      its non-apoptotic effects during pathogenesis of disease. CD95L is cleaved by
      metalloproteases and so exists in two different forms: a transmembrane form and a
      soluble ligand (s-CD95L). We recently observed that the soluble ligand is
      overexpressed in serum from patients with triple-negative breast cancer or SLE,
      in whom it contributes to disease severity by activating non-apoptotic signaling
      pathways and promoting either metastatic dissemination or accumulation of certain
      T cell subsets in damaged organs. Here, we discuss the roles of CD95 in
      modulating immune functions via induction of mainly non-apoptotic signaling
      pathways.

PMID- 29021796
TI  - Potassium in the Grape (Vitis vinifera L.) Berry: Transport and Function.
AB  - K+ is the most abundant cation in the grape berry. Here we focus on the most
      recent information in the long distance transport and partitioning of K+ within
      the grapevine and postulate on the potential role of K+ in berry sugar
      accumulation, berry water relations, cellular growth, disease resistance, abiotic
      stress tolerance and mitigating senescence. By integrating information from
      several different plant systems we have been able to generate new hypotheses on
      the integral functions of this predominant cation and to improve our
      understanding of how these functions contribute to grape berry growth and
      ripening. Valuable contributions to the study of K+ in membrane stabilization,
      turgor maintenance and phloem transport have allowed us to propose a mechanistic
      model for the role of this cation in grape berry development.

PMID- 29021798
TI  - QTLs and Potential Candidate Genes for Heat Stress Tolerance Identified from the
      Mapping Populations Specifically Segregating for Fv/Fm in Wheat.
AB  - Despite the fact that Fv/Fm (maximum quantum efficiency of photosystem II) is the
      most widely used parameter for a rapid non-destructive measure of stress
      detection in plants, there are barely any studies on the genetic understanding of
      this trait under heat stress. Our aim was to identify quantitative trait locus
      (QTL) and the potential candidate genes linked to Fv/Fm for improved
      photosynthesis under heat stress in wheat (Triticum aestivum L.). Three bi
      parental F2 mapping populations were generated by crossing three heat tolerant
      male parents (origin: Afghanistan and Pakistan) selected for high Fv/Fm with a
      common heat susceptible female parent (origin: Germany) selected for lowest Fv/Fm
      out of a pool of 1274 wheat cultivars of diverse geographic origin. Parents
      together with 140 F2 individuals in each population were phenotyped by Fv/Fm
      under heat stress (40 degrees C for 3 days) around anthesis. The Fv/Fm decreased
      by 6.3% in the susceptible parent, 1-2.5% in the tolerant parents and
      intermediately 4-6% in the mapping populations indicating a clear segregation for
      the trait. The three populations were genotyped with 34,955 DArTseq and 27 simple
      sequence repeat markers, out of which ca. 1800 polymorphic markers mapped to 27
      linkage groups covering all the 21 chromosomes with a total genome length of
      about 5000 cM. Inclusive composite interval mapping resulted in the
      identification of one significant and heat-stress driven QTL in each population
      on day 3 of the heat treatment, two of which were located on chromosome 3B and
      one on chromosome 1D. These QTLs explained about 13-35% of the phenotypic
      variation for Fv/Fm with an additive effect of 0.002-0.003 with the positive
      allele for Fv/Fm originating from the heat tolerant parents. Approximate physical
      localization of these three QTLs revealed the presence of 12 potential candidate
      genes having a direct role in photosynthesis and/or heat tolerance. Besides
      providing an insight into the genetic control of Fv/Fm in the present study, the
      identified QTLs would be useful in breeding for heat tolerance in wheat.

PMID- 29021797
TI  - The Rice AAA-ATPase OsFIGNL1 Is Essential for Male Meiosis.
AB  - Meiosis is crucial in reproduction of plants and ensuring genetic diversity.
      Although several genes involved in homologous recombination and DNA repair have
      been reported, their functions in rice (Oryza sativa) male meiosis remain poorly
      understood. Here, we isolated and characterized the rice OsFIGNL1 (OsFidgetin
      like 1) gene, encoding a conserved AAA-ATPase, and explored its function and
      importance in male meiosis and pollen formation. The rice Osfignl1 mutant
      exhibited normal vegetative growth, but failed to produce seeds and displayed
      pollen abortion phenotype. Phenotypic comparisons between the wild-type and
      Osfignl1 mutant demonstrated that OsFIGNL1 is required for anther development,
      and that the recessive mutation of this gene causes male sterility in rice.
      Complementation and CRISPR/Cas9 experiments demonstrated that wild-type OsFIGNL1
      is responsible for the male sterility phenotype. Subcellular localization showed
      that OsFIGNL1-green fluorescent protein was exclusively localized in the nucleus
      of rice protoplasts. Male meiosis in the Osfignl1 mutant exhibited abnormal
      chromosome behavior, including chromosome bridges and multivalent chromosomes at
      diakinesis, lagging chromosomes, and chromosome fragments during meiosis. Yeast
      two-hybrid assays demonstrated OsFIGNL1 could interact with RAD51A1, RAD51A2,
      DMC1A, DMC1B, and these physical interactions were further confirmed by BiFC
      assay. Taken together, our results suggest that OsFIGNL1 plays an important role
      in regulation of male meiosis and anther development.

PMID- 29021799
TI  - Improved Quantitative Plant Proteomics via the Combination of Targeted and
      Untargeted Data Acquisition.
AB  - Quantitative proteomics strategies - which are playing important roles in the
      expanding field of plant molecular systems biology - are traditionally designated
      as either hypothesis driven or non-hypothesis driven. Many of these strategies
      aim to select individual peptide ions for tandem mass spectrometry (MS/MS), and
      to do this mixed hypothesis driven and non-hypothesis driven approaches are
      theoretically simple to implement. In-depth investigations into the efficacies of
      such approaches have, however, yet to be described. In this study, using combined
      samples of unlabeled and metabolically 15N-labeled Arabidopsis thaliana proteins,
      we investigate the mixed use of targeted data acquisition (TDA) and data
      dependent acquisition (DDA) - referred to as TDA/DDA - to facilitate both
      hypothesis driven and non-hypothesis driven quantitative data collection in
      individual LC-MS/MS experiments. To investigate TDA/DDA for hypothesis driven
      data collection, 7 miRNA target proteins of differing size and abundance were
      targeted using inclusion lists comprised of 1558 m/z values, using 3 different
      TDA/DDA experimental designs. In samples in which targeted peptide ions were of
      particularly low abundance (i.e., predominantly only marginally above mass
      analyser detection limits), TDA/DDA produced statistically significant increases
      in the number of targeted peptides identified (230 +/- 8 versus 80 +/- 3 for DDA;
      p = 1.1 * 10-3) and quantified (35 +/- 3 versus 21 +/- 2 for DDA; p = 0.038) per
      experiment relative to the use of DDA only. These expected improvements in
      hypothesis driven data collection were observed alongside unexpected improvements
      in non-hypothesis driven data collection. Untargeted peptide ions with m/z values
      matching those in inclusion lists were repeatedly identified and quantified
      across technical replicate TDA/DDA experiments, resulting in significant
      increases in the percentages of proteins repeatedly quantified in TDA/DDA
      experiments only relative to DDA experiments only (33.0 +/- 2.6% versus 8.0 +/-
      2.7%, respectively; p = 0.011). These results were observed together with
      uncompromised broad-scale MS/MS data collection in TDA/DDA experiments relative
      to DDA experiments. Using our observations we provide guidelines for TDA/DDA
      method design for quantitative plant proteomics studies, and suggest that TDA/DDA
      is a broadly underutilized proteomics data acquisition strategy.

PMID- 29021800
TI  - Strigolactones Improve Plant Growth, Photosynthesis, and Alleviate Oxidative
      Stress under Salinity in Rapeseed (Brassica napus L.) by Regulating Gene
      Expression.
AB  - Rapeseed (Brassica napus L.) is a very important edible oil crop in the world,
      and the production is inhibited by abiotic stresses, such as salinity. Plant
      hormones can alleviate the stress by regulating the physiological processes and
      gene expression. To study the plant responses to salinity in combination with
      GR24, a synthesized strigolactone, the oilseed rape variety (Zhongshuang 11)
      replications were grown in the pots in a controlled growth chamber under three
      levels of salinity (0, 100, and 200 mM NaCl) and 0.18 MUM GR24 treatments at the
      seedling stage for 7 days. The results showed that salinity depressed the shoots
      and roots growth, whereas GR24 improved the growth under salt stress. Leaf
      chlorophyll contents and gas exchange parameters (net photosynthetic rates,
      stomatal conductance, intercellular CO2 concentration, and transpiration rate)
      were also reduced significantly with increasing salinity, and these effects could
      be partially reversed by GR24 application. Additionally, GR24 treatment
      significantly increased and decreased the photosystem II quantum yield and non
      photochemical quenching, respectively, under salinity stress conditions. The
      activities of peroxidase and superoxide dismutase increased, and lipid
      peroxidation measured by the level of malondialdehyde reduced due to GR24
      application. The transcriptome analysis of root and shoot was conducted. Three
      hundred and forty-two common differentially expressed genes (DEGs) after GR24
      treatment and 166 special DEGs after GR24 treatment under salinity stress were
      identified in root and shoot. The DEGs in root were significantly more than that
      in shoot. Quantitative PCR validated that the stress alleviation was mainly
      related to the gene expression of tryptophan metabolism, plant hormone signal
      transduction, and photosynthesis.

PMID- 29021802
TI  - Genome-Wide Identification of Circular RNAs in Arabidopsis thaliana.
AB  - Circular RNAs (circRNAs) are a family of transcripts with covalently closed
      circular structures and still largely unknown functions. Large numbers of
      circRNAs have been found in various biological processes in humans and animals,
      but fewer circRNAs have been identified in plants. We performed a genome-wide
      analysis of circRNAs in Arabidopsis thaliana via deep sequencing. We constructed
      14 strand-specific libraries from 13 samples of plants from four developmental
      stages, four stress treatments, and five organs and a mixed sample across the
      lifespan. In total, we identified 5861 circRNAs, including 1275 novel ones, using
      the strict threshold of at least two unique back-spliced supporting reads. The
      circRNAs were non-randomly distributed in all chromosomes; most were exonic.
      Sequence similarity analysis of circRNAs between A. thaliana and four other
      species showed that some circRNAs are conserved in plants. Functional annotation
      indicated that many parent genes of circRNAs are involved in many fundamental
      processes including plant development, reproduction, and response to stimulus. In
      addition, a small proportion of circRNAs was shown to be potential targets of
      miRNAs, indicating that the circRNAs could interact with miRNAs to regulate gene
      expression. qRT-PCR analysis revealed that circRNAs displayed diverse expression
      patterns at different growth stages. Our results provide an important resource
      for continuing circRNA research in A. thaliana, and should enhance our
      understanding of circRNAs in plants.

PMID- 29021803
TI  - UAV-Based Thermal Imaging for High-Throughput Field Phenotyping of Black Poplar
      Response to Drought.
AB  - Poplars are fast-growing, high-yielding forest tree species, whose cultivation as
      second-generation biofuel crops is of increasing interest and can efficiently
      meet emission reduction goals. Yet, breeding elite poplar trees for drought
      resistance remains a major challenge. Worldwide breeding programs are largely
      focused on intra/interspecific hybridization, whereby Populus nigra L. is a
      fundamental parental pool. While high-throughput genotyping has resulted in
      unprecedented capabilities to rapidly decode complex genetic architecture of
      plant stress resistance, linking genomics to phenomics is hindered by technically
      challenging phenotyping. Relying on unmanned aerial vehicle (UAV)-based remote
      sensing and imaging techniques, high-throughput field phenotyping (HTFP) aims at
      enabling highly precise and efficient, non-destructive screening of genotype
      performance in large populations. To efficiently support forest-tree breeding
      programs, ground-truthing observations should be complemented with standardized
      HTFP. In this study, we develop a high-resolution (leaf level) HTFP approach to
      investigate the response to drought of a full-sib F2 partially inbred population
      (termed here 'POP6'), whose F1 was obtained from an intraspecific P. nigra
      controlled cross between genotypes with highly divergent phenotypes. We assessed
      the effects of two water treatments (well-watered and moderate drought) on a
      population of 4603 trees (503 genotypes) hosted in two adjacent experimental
      plots (1.67 ha) by conducting low-elevation (25 m) flights with an aerial drone
      and capturing 7836 thermal infrared (TIR) images. TIR images were undistorted,
      georeferenced, and orthorectified to obtain radiometric mosaics. Canopy
      temperature (Tc) was extracted using two independent semi-automated segmentation
      techniques, eCognition- and Matlab-based, to avoid the mixed-pixel problem.
      Overall, results showed that the UAV platform-based thermal imaging enables to
      effectively assess genotype variability under drought stress conditions. Tc
      derived from aerial thermal imagery presented a good correlation with ground
      truth stomatal conductance (gs) in both segmentation techniques. Interestingly,
      the HTFP approach was instrumental to detect drought-tolerant response in 25% of
      the population. This study shows the potential of UAV-based thermal imaging for
      field phenomics of poplar and other tree species. This is anticipated to have
      tremendous implications for accelerating forest tree genetic improvement against
      abiotic stress.

PMID- 29021801
TI  - Inspirations on Virus Replication and Cell-to-Cell Movement from Studies
      Examining the Cytopathology Induced by Lettuce infectious yellows virus in Plant
      Cells.
AB  - Lettuce infectious yellows virus (LIYV) is the type member of the genus
      Crinivirus in the family Closteroviridae. Like many other positive-strand RNA
      viruses, LIYV infections induce a number of cytopathic changes in plant cells, of
      which the two most characteristic are: Beet yellows virus-type inclusion bodies
      composed of vesicles derived from cytoplasmic membranes; and conical plasmalemma
      deposits (PLDs) located at the plasmalemma over plasmodesmata pit fields. The
      former are not only found in various closterovirus infections, but similar
      structures are known as 'viral factories' or viroplasms in cells infected with
      diverse types of animal and plant viruses. These are generally sites of virus
      replication, virion assembly and in some cases are involved in cell-to-cell
      transport. By contrast, PLDs induced by the LIYV-encoded P26 non-virion protein
      are not involved in replication but are speculated to have roles in virus
      intercellular movement. These deposits often harbor LIYV virions arranged to be
      perpendicular to the plasma membrane over plasmodesmata, and our recent studies
      show that P26 is required for LIYV systemic plant infection. The functional
      mechanism of how LIYV P26 facilitates intercellular movement remains unclear,
      however, research on other plant viruses provides some insights on the possible
      ways of viral intercellular movement through targeting and modifying
      plasmodesmata via interactions between plant cellular components and viral
      encoded factors. In summary, beginning with LIYV, we review the studies that have
      uncovered the biological determinants giving rise to these cytopathological
      effects and their importance in viral replication, virion assembly and
      intercellular movement during the plant infection by closteroviruses, and compare
      these findings with those for other positive-strand RNA viruses.

PMID- 29021805
TI  - Concurrent Effects of Sediment Accretion and Nutrient Availability on the Clonal
      Growth Strategy of Carex brevicuspis-A Wetland Sedge That Produces Both Spreading
      and Clumping Ramets.
AB  - Clonal plants producing both clumping and spreading ramets can adjust their
      growth forms in response to resource heterogeneity or environmental stress. They
      might produce clumping ramets to retain favorable patches, or produce spreading
      ramets to escape from stress-affected patches. This study aimed to investigate
      the rarely reported concurrent effects of sediment accretion and nutrient
      enrichment, which often occur simultaneously in lacustrine wetlands, on the
      vegetative propagation and clonal growth forms of Carex brevicuspis C.B. Clarke
      by conducting a factorial experiment of sediment burial and nutrient addition.
      Biomass accumulation, new ramet and rhizome numbers, and ramet length of C.
      brevicuspis were not affected at moderate burial, but were significantly lower
      after deep burial. Similarly, nutrient enrichment increased the growth and
      vegetative propagation of C. brevicuspis up to moderate sediment burial, but not
      after deep burial. Sediment accretion increased the proportion of spreading
      ramets produced by C. brevicuspis, whereas nutrient addition had no effect on the
      clonal growth forms. Our results indicated that the plasticity of clonal growth
      forms is an effective strategy used by plants to acclimate to moderate sediment
      accretion. Nutrient enrichment did not influence the clonal growth forms of C.
      brevicuspis and could not facilitate its acclimation to heavy sedimentation
      condition.

PMID- 29021804
TI  - Calcium and Calmodulin Are Involved in Nitric Oxide-Induced Adventitious Rooting
      of Cucumber under Simulated Osmotic Stress.
AB  - Osmotic stress is a major form of abiotic stress that adversely affects growth
      and development of plants and subsequently reduces yield and quality of crops. In
      this study, the effect of nitric oxide (NO) and calcium (Ca2+) on the process of
      adventitious rooting in cucumber (Cucumis sativus L.) under simulated osmotic
      stress was investigated. The results revealed that the effect of exogenous NO and
      Ca2+ in promoting the development of adventitious roots in cucumber seedlings
      under simulated osmotic stress was dose-dependent, with a maximal biological
      response at 10 MUM NO donor nitroprusside (SNP) or 200 MUM Ca2+. The application
      of Ca2+ chelators or channel inhibitors and calmodulin (CaM) antagonists
      significantly reversed NO-induced adventitious rooting, implying that endogenous
      Ca2+/CaM might be involved in NO-induced adventitious rooting under osmotic
      stress. Moreover, intracellular Ca amount was also increased by NO in cucumber
      hypocotyls during the development of adventitious roots under osmotic stress.
      This increase of endogenous Ca2+ was inhibited by NO specific scavenger 2-(4
      carboxyphenyl) -4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt
      (cPTIO), nitrate reductase inhibitors tungstate (Na2WO4) and sodium azide (NaN3).
      This gives an indication that Ca2+ might be a downstream signaling molecule in
      the adventitious root development by NO under osmotic condition. The results also
      show that NO or Ca2+ play a positive role in improving plant water status and
      photosynthetic system by increasing chlorophyll content and photochemical
      activity in leaves. Furthermore, NO and Ca2+ treatment might alleviate the
      negative effects of osmotic stress by decreasing membrane damage and reactive
      oxygen species (ROS) production by enhancing the activities of superoxide
      dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX). Therefore,
      Ca2+/CaM may act as a downstream signaling molecule in NO-induced development of
      adventitious root under simulated osmotic stress through improving the
      photosynthetic performance of leaves and activating antioxidative system in
      plants.

PMID- 29021806
TI  - ERECTA Regulates Cell Elongation by Activating Auxin Biosynthesis in Arabidopsis
      thaliana.
AB  - The ERECTA family genes, ERECTA (ER), ERECTA-LIKE1 (ERL1), and ERECTA-LIKE2
      (ERL2), encode leucine-rich repeat receptor-like kinases in Arabidopsis thaliana.
      Knocking out these three genes can cause severe phenotypes, which indicates that
      they play significant roles in plant growth and development. However, the
      molecular mechanism within remains unclear. Here we show that the short hypocotyl
      phenotypes of er erl1 erl2 mutants are mainly due to the defects of cell
      elongation rather than the cell division. In contrast, in the ERECTA
      overexpression transgenic plants, the hypocotyl length is increased with
      elongated cells. Moreover, we show that the er erl1 erl2 triple mutant contains a
      low level of auxin, and the expression levels of the key auxin biosynthesis genes
      are significantly reduced. Consistent with this observation, increasing exogenous
      or endogenous auxin levels could partially rescue the cell elongation defects of
      the er erl1 erl2 triple mutant. Therefore, our results provide a molecular basis
      for auxin mediated ERECTA control of the hypocotyl length in Arabidopsis
      thaliana.

PMID- 29021807
TI  - C4 Protein of Sweet Potato Leaf Curl Virus Regulates Brassinosteroid Signaling
      Pathway through Interaction with AtBIN2 and Affects Male Fertility in
      Arabidopsis.
AB  - Sweepoviruses have been identified globally and cause substantial yield losses
      and cultivar decline in sweet potato. This study aimed to investigate the
      interaction between sweepovirus and plant host by analyzing the function of the
      viral protein C4 of Sweet potato leaf curl virus-Jiangsu (SPLCV-JS), a
      sweepovirus cloned from diseased sweet potato plants in East China. Ectopic
      expression of the C4 in Arabidopsis altered plant development drastically with
      phenotypic changes including leaf curling, seedling twisting, deformation of
      floral tissues and reduction of pollen fertility, and seed number. Using
      bimolecular fluorescence complementation analysis, this study demonstrated that
      the SPLCV-JS C4 protein interacted with brassinosteroid-insensitive 2 (AtBIN2) in
      the plasma membrane of Nicotiana benthamiana cells. The C4 AtBIN2 interaction was
      further confirmed by yeast two-hybrid assays. This interaction led to the re
      localization of AtBIN2-interacting proteins AtBES1/AtBZR1 into the nucleus which
      altered the expression of brassinosteroid (BR)-response genes, resulting in the
      activation of BR-signaling pathway. The interaction of SPLCV-JS C4 and AtBIN2
      also led to the down-regulated expression of key genes involved in anther and
      pollen development, including SPROROCYTELESS/NOZZLE, DEFECTIVE IN TAPEL
      DEVELOPMENT AND FUNCTION 1, and ABORTED MICROSPORES, which caused abnormal
      tapetal development, followed by defective exine pattern formation of microspores
      and pollen release. Consequently, male fertility in the C4 transgenic Arabidopsis
      was reduced. The present study illustrated how the sweepovirus C4 protein
      functioned in host cells and affected male fertility by interacting with the key
      components of BR-signaling pathway.

PMID- 29021809
TI  - Erratum to: Appraisal of testicular volumes: volumes matching ultrasound values
      referenced to stages of genital development.
AB  - [This corrects the article DOI: 10.1186/s13633-017-0046-x.].

PMID- 29021808
TI  - Brassinosteroids Regulate OFP1, a DLT Interacting Protein, to Modulate Plant
      Architecture and Grain Morphology in Rice.
AB  - Brassinosteroids (BRs) regulate important agronomic traits in rice, including
      plant height, leaf angle, and grain size. However, the underlying mechanisms
      remain not fully understood. We previously showed that GSK2, the central negative
      regulator of BR signaling, targets DLT, the GRAS family protein, to regulate BR
      responses. Here, we identified Ovate Family Protein 1 (OFP1) as a DLT interacting
      protein. OFP1 was ubiquitously expressed and the protein was localized in both
      cytoplasm and nucleus. Overexpression of OFP1 led to enlarged leaf angles,
      reduced plant height, and altered grain shape, largely resembled DLT
      overexpression plants. Genetic analysis showed that the regulation of plant
      architecture by OFP1 depends on DLT function. In addition, we found OFP1 was
      greatly induced by BR treatment, and OsBZR1, the critical transcription factor of
      BR signaling, was physically associated with the OFP1 promoter. Moreover, we
      showed that gibberellin synthesis was greatly repressed in OFP1 overexpression
      plants, suggesting OFP1 participates in the inhibition of plant growth by high BR
      or elevated BR signaling. Furthermore, we revealed that OFP1 directly interacts
      with GSK2 kinase, and inhibition of the kinase activity significantly promotes
      OFP1 protein accumulation in plant. Taken together, we identified OFP1 as an
      additional regulator of BR responses and revealed how BRs promote OFP1 at both
      transcription and protein levels to modulate plant architecture and grain
      morphology in rice.

PMID- 29021810
TI  - Perihepatic cystic mass: Zebra or horse?

PMID- 29021811
TI  - Significance of finding benign endometrial cells in women 40-45 versus 46 years
      or older on Papanicolaou tests and histologic follow-up.
AB  - BACKGROUND: The 2014 Bethesda System recommends reporting the finding of benign
      appearing, exfoliated endometrial cells on Papanicolaou (Pap) tests in women aged
      45 years and older. We aimed to determine the significance of normal endometrial
      cells on liquid-based Pap tests in women aged 40 years and older and to correlate
      this finding with clinical factors and cytologic/histologic follow-up. MATERIALS
      AND METHODS: We retrospectively identified all women aged 40 years and older who
      had benign endometrial cells (BECs) on Pap tests at our institution during a 6
      year period. Histologic follow-up and outcomes were evaluated. RESULTS: Among
      18,850 Pap tests during the study period, 255 (1.4%) had findings of BECs and 159
      (62.4%) of these women had follow-up Pap tests or subsequent tissue sampling by
      surgical procedures. Of the 159 cases, only 4 (2.5%) had significant endometrial
      pathologic processes, all endometrial endometrioid adenocarcinoma (three women
      had postmenopausal bleeding and 1 was perimenopausal with menorrhagia). No women
      between ages 40 and 45 years had significant pathologic findings and only one
      woman between 46 and 50 years (47 years) had an endometrial endometrioid
      carcinoma (1.5%). Women older than 47 years have higher odds (5.38) of having a
      significant endometrial lesion (P = 0.029) than those who are <=47. CONCLUSION:
      Clinically significant endometrial lesions occurred predominantly in women older
      than 50 years (4.6%) and in only one woman between ages 46 and 50 years (1.5%).
      Therefore, endometrial sampling should be performed in women aged 47 years and
      older with BECs, especially when additional clinical indicators (e.g.,
      postmenopausal bleeding) are recognized.

PMID- 29021812
TI  - Fine needle aspiration of spindle cell ductal carcinoma in situ of the breast: A
      case report and the use of ancillary tests for the differential diagnosis of
      metaplastic carcinoma.
AB  - Spindle cell ductal carcinoma in situ (DCIS) is a recently recognized subtype of
      DCIS, which is associated with a very rare and unique morphology. Although the
      histologic features have been relatively well described in a few reports, the
      cytologic features have not. Even though the distinction of this lesion from
      usual DCIS is not crucial clinically, it should be noted that this lesion might
      simulate the features of metaplastic carcinoma on fine needle aspiration
      cytology. Here, we report a case of spindle cell DCIS in a 45-year-old female,
      with the detailed cytologic features, both on conventional and liquid-based
      preparations, along with some useful immunohistochemical staining markers for the
      differential diagnosis.

PMID- 29021813
TI  - Effect of a short-term dietary supplementation with phytosterols, red yeast rice
      or both on lipid pattern in moderately hypercholesterolemic subjects: a three
      arm, double-blind, randomized clinical trial.
AB  - BACKGROUND: Phytosterols and red yeast rice are largely studied cholesterol
      lowering nutraceuticals, respectively inhibiting the bowel absorption and liver
      synthesis of cholesterol. Our aim was to test the effect on lipid profile of
      phytosterols, red yeast rice and their association. METHODS: We performed a three
      parallel arms, double blind, clinical trial randomizing 90 moderately
      hypercholesterolemic subjects to treatment with phytosterols 800 mg (group 1),
      red yeast rice standardized to contain 5 mg monacolins from Monascus purpureus
      (group 2), or both combined nutraceuticals (group 3). RESULTS: After 8 weeks of
      treatment, in group 1 no significant variation of lipid parameters has been
      detected. In group 2 a significant reduction (p < 0.001) of LDL-Cholesterol (
      20.5% vs. baseline) and Apolipoprotein B (-14.4% vs. baseline) as it occurred in
      group 3 (LDL-Cholesterol vs. baseline: -27.0%, Apolipoprotein B vs. baseline: 
      19.0%) (P < 0.001). LDL-Cholesterol and Apolipoprotein B changes were
      significantly different comparing group 2 with group 1 (P < 0.05), and group 3
      with group 1 (P < 0.05). LDL-Cholesterol change was also significantly higher in
      group 3 than in group 2 (P < 0.05). CONCLUSION: The association of phytosterol
      and red yeast rice seems to have additive cholesterol lowering effect, reaching a
      clinically significant LDL-Cholesterol reduction in mildly hypercholesterolemic
      patients. TRIAL REGISTRATION: ClinicalTrial.gov ID: NCT02603276, Registered
      27/08/2015.

PMID- 29021814
TI  - Sex-specific association between fibroblast growth factor 21 and type 2 diabetes:
      a nested case-control study in Singapore Chinese men and women.
AB  - BACKGROUND: Fibroblast growth factor 21 (FGF-21) is mainly secreted by liver and
      has been reported to be involved in the pathogenesis of type 2 diabetes. Some
      prospective studies have shown a positive association between FGF-21 and diabetes
      risk. However, no study has examined whether the association differed by sex,
      which has been reported between FGF-21 and atherosclerosis. Therefore, we
      prospectively evaluated the sex-specific association between FGF-21 and diabetes
      in a Chinese population. METHODS: Serum FGF-21 concentration was measured in a
      case-control study comprising of 251 incident diabetes cases and 251 age-sex
      matched controls nested within a prospective population-based cohort, the
      Singapore Chinese Health Study. At blood collection between 1999 and 2004,
      participants were free of diagnosed diabetes, cardiovascular disease, and cancer.
      Incident self-reported diabetes cases were identified at follow-up II interview
      (2006-2010). Odds ratio (OR) and 95% confidence interval (CI) were calculated
      using multivariable logistic regression models. RESULTS: After adjustment for
      risk biomarkers of diabetes including lipids, liver enzymes and inflammatory
      marker, the OR of type 2 diabetes with per one unit increment in log FGF-21
      concentration was 1.16 (95% CI 0.90-1.50). Significant interaction was found with
      sex (P-interaction = 0.029): the OR (95% CI) was 1.50 (1.00-2.25) in women and
      0.89 (0.52-1.53) in men. CONCLUSIONS: Higher serum FGF-21 level was associated
      with an increased risk of diabetes in Chinese women but not in men. The sex
      difference in the association between FGF-21 and diabetes risk deserves further
      investigation and replication in other populations.

PMID- 29021815
TI  - Analysis of EEG entropy during visual evocation of emotion in schizophrenia.
AB  - BACKGROUND: In this study, the international affective picture system was used to
      evoke emotion, and then the corresponding signals were collected. The features
      from different points of brainwaves, frequency, and entropy were used to identify
      normal, moderately, and markedly ill schizophrenic patients. METHODS: The signals
      were collected and preprocessed. Then, the signals were separated according to
      three types of emotions and five frequency bands. Finally, the features were
      calculated using three different methods of entropy. For classification, the
      features were divided into different sections and classification using support
      vector machine (principal components analysis on 95%). Finally, simple regression
      and correlation analysis between the total scores of positive and negative
      syndrome scale and features were used. RESULTS: At first, we observed that to
      classify normal and markedly ill schizophrenic patients, the identification
      result was as high as 81.5%, and therefore, we further explored moderately and
      markedly ill schizophrenic patients. Second, the identification rate in both
      moderately and markedly ill schizophrenic patient was as high as 79.5%, which at
      the Fz point signal in high valence low arousal fragments was calculated using
      the ApEn methods. Finally, the total scores of positive and negative syndrome
      scale were used to analyze the correlation with the features that were the five
      frequency bands at the Fz point signal. The results show that the p value was
      less than .001 at the beta wave in the 15-18 Hz frequency range.

PMID- 29021816
TI  - Determinants of early initiation of breastfeeding in rural Niger: cross-sectional
      study of community based child healthcare promotion.
AB  - BACKGROUND: Most child deaths are preventable and caused by behaviorally
      modifiable factors. By promoting optimal breastfeeding, we can reduce neonatal
      and child mortality risks by 45%. This paper provides new family and community
      based perspectives to identify factors interfering with the program impact on
      promoting early initiation of breastfeeding among the most vulnerable populations
      in rural Niger. METHODS: A secondary analysis of a retrospective cross-sectional
      study evaluated a UNICEF behavior change program on child healthcare. The study
      sample is based on a post-hoc constitution of two groups exposed and unexposed to
      the program. All women (n = 1026) aged 14-49 years having at least one child
      below 24 months of age were included. We measured crude and adjusted odds ratios
      with chi-square and multivariate logistic regression models. RESULTS: Independent
      variables shown to be associated with early breastfeeding include sales
      activities compared to household work with no direct income (AOR 7.7; 95% CI 1.3,
      47.8) and mutual decision for harvest use (AOR 8.6; 95% CI 2.0, 36.8). Antenatal
      care did not modify the timing of breastfeeding initiation. CONCLUSIONS: A high
      risk group of mothers with social and economic vulnerability are prone to
      suboptimal breastfeeding within the first hour of birth. Support from family and
      neighbors positively influenced early breastfeeding. Those who had no direct
      income and limited access to health services were a high-risk group, prone to
      delayed initiation of breastfeeding.

PMID- 29021817
TI  - A dual isotopic approach using radioactive phosphorus and the isotopic
      composition of oxygen associated to phosphorus to understand plant reaction to a
      change in P nutrition.
AB  - BACKGROUND: Changing the phosphorus (P) nutrition leads to changes in plant
      metabolism. The aim of this study was to investigate how these changes are
      reflected in the distribution of 33P and the isotopic composition of oxygen
      associated to P (delta18OP) in different plant parts of soybean (Glycine max cv.
      Toliman). Two P pools were extracted sequentially with 0.3 M trichloroacetic acid
      (TCA P) and 10 M nitric acid (HNO3; residual P). RESULTS: The delta18OP of TCA P
      in the old leaves of the - P plants (23.80/00) significantly decreased compared
      to the + P plants (27.40/00). The 33P data point to an enhanced mobilisation of P
      from residual P in the old leaves of the - P plants compared to the + P plants.
      CONCLUSIONS: Omitting P for 10 days lead to a translocation of P from source to
      sink organs in soybeans. This was accompanied by a significant lowering of the
      delta18OP of TCA P in the source organs due to the enzymatic hydrolysis of
      organic P. Combining 33P and delta18OP can provide useful insights in plant
      responses to P omission at an early stage.

PMID- 29021818
TI  - Algorithms for matching partially labelled sequence graphs.
AB  - BACKGROUND: In order to find correlated pairs of positions between proteins,
      which are useful in predicting interactions, it is necessary to concatenate two
      large multiple sequence alignments such that the sequences that are joined
      together belong to those that interact in their species of origin. When each
      protein is unique then the species name is sufficient to guide this match,
      however, when there are multiple related sequences (paralogs) in each species
      then the pairing is more difficult. In bacteria a good guide can be gained from
      genome co-location as interacting proteins tend to be in a common operon but in
      eukaryotes this simple principle is not sufficient. RESULTS: The methods
      developed in this paper take sets of paralogs for different proteins found in the
      same species and make a pairing based on their evolutionary distance relative to
      a set of other proteins that are unique and so have a known relationship
      (singletons). The former constitute a set of unlabelled nodes in a graph while
      the latter are labelled. Two variants were tested, one based on a phylogenetic
      tree of the sequences (the topology-based method) and a simpler, faster variant
      based only on the inter-sequence distances (the distance-based method). Over a
      set of test proteins, both gave good results, with the topology method performing
      slightly better. CONCLUSIONS: The methods develop here still need refinement and
      augmentation from constraints other than the sequence data alone, such as known
      interactions from annotation and databases, or non-trivial relationships in
      genome location. With the ever growing numbers of eukaryotic genomes, it is hoped
      that the methods described here will open a route to the use of these data equal
      to the current success attained with bacterial sequences.

PMID- 29021819
TI  - HIV-1 matrix protein p17 and its variants promote human triple negative breast
      cancer cell aggressiveness.
AB  - BACKGROUND: The introduction of cART has changed the morbidity and mortality
      patterns affecting HIV-infected (HIV+) individuals. The risk of breast cancer in
      HIV+ patients has now approached the general population risk. However, breast
      cancer has a more aggressive clinical course and poorer outcome in HIV+ patients
      than in general population, without correlation with the CD4 or virus particles
      count. These findings suggest a likely influence of HIV-1 proteins on breast
      cancer aggressiveness and progression. The HIV-1 matrix protein (p17) is
      expressed in different tissues and organs of successfully cART-treated patients
      and promotes migration of different cells. Variants of p17 (vp17s), characterized
      by mutations and amino acid insertions, differently from the prototype p17
      (refp17), also promote B-cell proliferation and transformation. METHODS: Wound
      healing assay, matrigel-based invasion assay, and anchorage-independent
      proliferation assay were employed to compare the biological activity exerted by
      refp17 and three different vp17s on the triple-negative human breast cancer cell
      line MDA-MB 231. Intracellular signaling was investigated by western blot
      analysis. RESULTS: Motility and invasiveness increased in cells treated with both
      refp17 and vp17s compared to untreated cells. The effects of the viral proteins
      were mediated by binding to the chemokine receptor CXCR2 and activation of the
      ERK1/2 signaling pathway. However, vp17s promoted MDA-MB 231 cell growth and
      proliferation in contrast to refp17-treated or not treated cells. CONCLUSIONS: In
      the context of the emerging role of the microenvironment in promoting and
      supporting cancer cell growth and metastatic spreading, here we provide the first
      evidence that exogenous p17 may play a crucial role in sustaining breast cancer
      cell migration and invasiveness, whereas some p17 variants may also be involved
      in cancer cell growth and proliferation.

PMID- 29021820
TI  - Introduction of p16INK4a as a surrogate biomarker for HPV in women with invasive
      cervical cancer in Sudan.
AB  - BACKGROUND: Cervical cancer is the fourth most common cancer in women worldwide
      with highest incidence reported in Eastern Africa in 2012. The primary goal of
      this study was to study the expression of p16INK4a in squamous cell carcinoma
      (SCC) of the cervix by immunohistochemistry (IHC) and determine relation with
      clinico-pathological parameters. This study further explored the correlation of
      p16INK4a immunostaining with another proliferation marker, Ki-67 and to study if
      human papillomavirus (HPV) IHC can be used as a marker for detection of virus in
      high-grade dysplasia. METHODS: A total of 90 samples, diagnosed for cervical
      cancer, were included in the study. Fixed Paraffin Embedded (FFPE) tissue
      sections were stained with anti-p16INK4a, anti-Ki-67 and anti-HPV antibodies
      using automated immunohistochemistry platform (ASLink 48-DAKO). RESULTS:
      Immunohistochemical protein expression of p16INK4a positivity was found to be
      highest in SCC (92.2%, n = 71) than other HPV tumors (76.9%, n = 10). The
      majority of cases (97.4%) were p16INK4a positive in the age group 41-60 years. In
      addition, a statistically significant difference between p16INK4a and HPV was
      observed among total cervical tumor cases and SCC cases. CONCLUSIONS: As expected
      staining of invasive cervical cancer with anti-HPV showed rare positivity because
      HPV heralds active infection in dysplastic lesions and not of frank cervical
      carcinoma. In contrast, anti-p16INK4a IHC results showed positive correlation in
      SCC and other cervical tumors.

PMID- 29021821
TI  - Utilization of traditional, complementary and alternative medicine and mental
      health among patients with chronic diseases in primary health care settings in
      Cambodia.
AB  - BACKGROUND: Coping with chronic illnesses often involves major lifestyle changes
      that may lead to poor mental health. Furthermore, in order to treat the chronic
      conditions, many sufferers in Asia turn to traditional, complementary and
      alternative medicines (TCAM). This study explores prevalence of TCAM use and
      factors associated with anxiety and depressive symptoms among patients with
      chronic diseases in Cambodia. METHODS: In 2015, this cross-sectional study was
      conducted with outpatients receiving treatment and care for chronic diseases in
      two urban and two rural primary health centers. Every eligible patient was
      randomly selected at the health centers using a systematic sampling procedure.
      Symptoms of anxiety and depression were assessed by using the Hospital Anxiety
      and Depression Scale (HADS). Multivariate logistic regression models were
      constructed to explore factors associated with anxiety and depressive symptoms.
      RESULTS: The study participants included 1528 patients, of whom 77.2% were
      female, with a mean age of 46.5 years (SD = 15.3). After adjustment, patients
      with depressive symptoms remained significantly more likely to be in the age
      groups between 41 and 60 years old and to be married, separated/divorced or
      widowed compared to those without depressive symptoms. Regarding the use of TCAM,
      patients with depressive symptoms remained significantly more likely to report
      using an herbalist, practicing visualization and praying for own health, but less
      likely to report using vitamins or supplements in the past 12 months. For quality
      of life, patients with depressive symptoms remained significantly less likely to
      agree that they had enough energy for their everyday life and had enough money to
      meet their daily needs. Similar risk factors were also found to be significantly
      associated with anxiety symptoms. CONCLUSIONS: Cambodian patients with chronic
      diseases who experienced symptoms of anxiety or depression were more likely to
      report reduced quality of life, greater chronic disease-related stigma and more
      TCAM use. Given the potential interaction of TCAM, mental health and other
      chronic conditions, a history of TCAM use and mental health should be elicited in
      clinical practices in primary health care settings, particularly in developing
      countries.

PMID- 29021822
TI  - A review of web-based support systems for students in higher education.
AB  - BACKGROUND: Recent evidence suggests that there is an increasing need for
      accessible and anonymous services to support higher education (HE) students
      suffering from psychological and/or academic difficulties. Such difficulties can
      lead to several negative outcomes, including poor academic performance, sub
      optimal mental health, reduced study satisfaction, and dropout from study.
      Currently, universities in the UK lack financial resources and the on-campus
      mental health services traditionally offered to students are increasingly
      economically unsustainable. Compounded by the perceived stigma of using such
      services, mental health providers have been driven to address the escalating
      needs of students through online services. METHODS: In this paper, we review
      online support systems identified through a literature search and a manual search
      of references in the identified papers. Further systems were identified through
      web searches, and systems still in development were identified by consultation
      with researchers in the field. We accessed systems online to extract relevant
      information, regarding the main difficulties addressed by the systems, the
      psychological techniques used and any relevant research evidence to support their
      effectiveness. CONCLUSION: A large number of web-based support systems have been
      developed to support mental health and wellbeing, although few specifically
      target HE students. Further research is necessary to establish the effectiveness
      of such interventions in providing a cost-effective alternative to face-to-face
      therapy, particularly in certain settings such as HE institutions.

PMID- 29021823
TI  - Evidence-based guideline implementation of quality assurance and quality control
      procedures in the Saudi National Mental Health Survey.
AB  - BACKGROUND: The World Mental Health surveys have been known to apply high
      standards of quality control, but few studies have been published to document
      this. Furthermore, the effectiveness of quality control has rarely been reported
      in the Middle East. CASE PRESENTATION: The focus of this paper was to highlight
      the implementation of quality control procedures in the Saudi National Mental
      Health Survey under the World Mental Health Survey Consortium. The paper
      summarizes the guidelines implemented for the various phases of survey quality
      control-the quality assurance procedures, the quality control procedures and the
      quality control appraisal components-as per previously prescribed recommendations
      in literature. CONCLUSIONS: Survey quality management is a process and not
      reducible to a single event. Midstream corrections are warranted by detecting
      problems and intervening appropriately. The Saudi National Mental Health Survey
      implemented such procedures through continuous quality improvement.

PMID- 29021824
TI  - Intense/obsessional interests in children with gender dysphoria: a cross
      validation study using the Teacher's Report Form.
AB  - OBJECTIVE: This study assessed whether children clinically referred for gender
      dysphoria (GD) show symptoms that overlap with Autism Spectrum Disorder (ASD).
      Circumscribed preoccupations/intense interests and repetitive behaviors were
      considered as overlapping symptoms expressed in both GD and ASD. METHODS: To
      assess these constructs, we examined Items 9 and 66 on the Teacher's Report Form
      (TRF), which measure obsessions and compulsions, respectively. RESULTS: For Item
      9, gender-referred children (n = 386) were significantly elevated compared to the
      referred (n = 965) and non-referred children (n = 965) from the TRF
      standardization sample. For Item 66, gender-referred children were elevated in
      comparison to the non-referred children, but not the referred children.
      CONCLUSIONS: These findings provided cross-validation of a previous study in
      which the same patterns were found using the Child Behavior Checklist (Vanderlaan
      et al. in J Sex Res 52:213-19, 2015). We discuss possible developmental pathways
      between GD and ASD, including a consideration of the principle of equifinality.

PMID- 29021825
TI  - Suicidal deaths in elementary school students in Korea.
AB  - BACKGROUND: The purpose of this study was to determine the characteristics of
      childhood suicidal deaths among elementary school students that occurred from
      2011 to 2015 in Korea. METHODS: The report form of each suicide case by the
      teacher in charge to the Education Ministry was reviewed retrospectively.
      RESULTS: There were 19 suicidal deaths (12 boys, 7 girls) in elementary school
      students. The youngest case was a third grader (n = 1). Jumping from heights (n =
      12) was the most frequently used method. Most suicides (n = 12) were committed in
      their homes. CONCLUSION: These results highlight the alarming trend of early
      suicidal deaths and the importance of early suicide prevention strategies,
      especially in schools.

PMID- 29021826
TI  - Co-production of 11alpha-hydroxyprogesterone and ethanol using recombinant yeast
      expressing fungal steroid hydroxylases.
AB  - BACKGROUND: Bioethanol production from sustainable sources of biomass that limit
      effect on food production are needed and in a biorefinery approach co-products
      are desirable, obtained from both the plant material and from the microbial
      biomass. Fungal biotransformation of steroids was among the first industrial
      biotransformations allowing corticosteroid production. In this work, the
      potential of yeast to produce intermediates needed in corticosteroid production
      is demonstrated at laboratory scale following bioethanol production from
      perennial ryegrass juice. RESULTS: Genes encoding the 11alpha-steroid hydroxylase
      enzymes from Aspergillus ochraceus (11alpha-SHAoch) and Rhizopus oryzae
      (CYP509C12) transformed into Saccharomyces cerevisiae for heterologous
      constitutive expression in p425TEF. Both recombinant yeasts (AH22:p11alpha-SHAoch
      and AH22:p509C12) exhibited efficient progesterone bioconversion (on glucose
      minimal medial containing 300 uM progesterone) producing either 11alpha
      hydroxyprogesterone as the sole metabolite (AH22:p11alpha-SHAoch) or a 7:1
      mixture of 11alpha-hydroxyprogesterone and 6beta-hydroxyprogesterone
      (AH22:p509C12). Ethanol yields for AH22:p11alpha-SHAoch and AH22:p509C12 were
      comparable resulting in >=75% conversion of glucose to alcohol. Co-production of
      bioethanol together with efficient production of the 11-OH intermediate for
      corticosteroid manufacture was then demonstrated using perennial ryegrass juice.
      Integration of the 11alpha-SHAoch gene into the yeast genome (AH22:11alpha
      SHAoch+K) resulted in a 36% reduction in yield of 11alpha-hydroxyprogesterone to
      174 umol/L using 300 uM progesterone. However, increasing progesterone
      concentration to 955 uM and optimizing growth conditions increased 11alpha
      hydroxyprogesterone production to 592 umol/L product formed. CONCLUSIONS: The
      progesterone 11alpha-steroid hydroxylases from A. ochraceus and R. oryzae, both
      monooxygenase enzymes of the cytochrome P450 superfamily, have been functionally
      expressed in S. cerevisiae. It appears that these activities in fungi are not
      associated with a conserved family of cytochromes P450. The activity of the A.
      ochraceous enzyme was important as the specificity of the biotransformation
      yielded just the 11-OH product needed for corticosteroid production. The data
      presented demonstrate how recombinant yeast could find application in rural
      biorefinery processes where co-production of value-added products (11alpha
      hydroxyprogesterone and ethanol) from novel feedstocks is an emergent and
      attractive possibility.

PMID- 29021827
TI  - Coordination among the rearfoot, midfoot, and forefoot during walking.
AB  - BACKGROUND: Examining coordination between segments is essential for prevention
      and treatment of injuries. However, traditional methods such as ratio, cross
      correlation technique, and angle-time plot may not provide a complete
      understanding of intersegmental coordination. The present study aimed to quantify
      the coordination among the rearfoot, midfoot, and forefoot segments during
      walking. METHODS: Twenty healthy young men walked barefoot on a treadmill.
      Reflective markers were fixed to their right shank and foot based on the Leardini
      foot model. Three-dimensional joint angles were calculated at the distal segment,
      and were expressed relative to the adjacent proximal segment. The coupling angle
      representing intersegmental coordination was calculated by using the modified
      vector coding technique, and categorized into the following four coordination
      patterns: in-phase with proximal dominancy, in-phase with distal dominancy, tanti
      phase with proximal dominancy, and anti-phase with distal dominancy. RESULTS: The
      results showed that the midfoot was dominantly everted compared with the rearfoot
      and forefoot during the early stance (i.e., the rearfoot-midfoot coordination and
      midfoot-forefoot coordination were mainly in-phase with distal and proximal
      dominancy, respectively). CONCLUSION: This result may suggest that the midfoot
      plays a more significant role than the rearfoot and forefoot during early stance.
      The results of the present study can help in understanding the interaction of the
      intersegmental foot kinematic time series during walking. The results could be
      used as data to distinguish the presence of injuries or abnormal inter-segmental
      foot motions such as pes planus. Additionally, these data might be used in the
      future in a comparison with data on foot deformities.

PMID- 29021828
TI  - Endurance exercise training decreased serum levels of surfactant protein D and
      improved aerobic fitness of obese women with type-2 diabetes.
AB  - BACKGROUND: Surfactant protein D (SP-D) is a member of the collectin family and
      is an important component of the pulmonary innate host defense. To find the
      relationship between exercise training and SP-D in diabetes, we examined the
      possible effects of a 10-week endurance exercise-training program on serum levels
      of SP-D, leptin, lipid profile and insulin resistance in obese women with type-2
      diabetes mellitus (T2DM). METHODS: Twenty-two obese women with T2DM were randomly
      assigned to either exercise training (ET) or control (C) group. A subject dropped
      from ET group due to personal reasons and 1 subject dropped from C group due to
      commitment to experiments conditions. A total of twenty obese women with T2DM
      were randomly assigned into endurance exercise training (ET = 10) and control (C
      = 10) groups. The training group underwent a progressive endurance-training
      program for 10 weeks (running on a treadmill for 30-55 min/day at 50-75% heart
      rate reserve) and the control group did not participate in any exercise program.
      Venous blood samples were collected from both groups before and 72 h after the
      last session of exercise training for analysis of serum SP-D, leptin, lipid
      profile, glucose and insulin. Data were analyzed using 2 (group: control,
      endurance training) * 2 (time: pre, post) ANOVA with repeated measures on the
      second factor. Absolute changes from rest (? baseline) values were calculated
      according to the following formula: ((measure-baseline).baseline-1).100. Percent
      change between groups was analyzed using independent t-tests (p < 0.05). All
      analyses were completed using SPSS 19. RESULTS: The serum SP-D levels were
      decreased after exercise training in ET (? = - 78.78 +/- 17.14%, p = 0.001) when
      compare to C (? = 9.41 +/- 4.75%). Obese diabetic women in the ET group showed
      significantly lower serum leptin levels (8053.27 +/- 878.7 pg/ml, ? = - 26.97 +/-
      16.41%) when compared with women in the control group (9885.5 +/- 696 pg/ml, ? =
      7.02 +/- 3.46%, p = 0.003). Fasting glucose was favorably and significantly
      affected by the intervention (ET ? = - 17.01 +/- 12.74%, Control ? = 15.47 +/-
      7.32%, p = 0.011). VO2max as an index of aerobic fitness was significantly
      increased after 10-weeks of endurance exercise training (ET ? = 19.29 +/- 6.18%).
      CONCLUSIONS: Endurance exercise training with improvement in aerobic fitness
      induced a significant reduction of serum SP-D levels in obese women with T2DM.

PMID- 29021830
TI  - Emerging issues in public health: a perspective on Ghana's healthcare
      expenditure, policies and outcomes.
AB  - Ghana's healthcare expenditure has increased over the past two decades. Increased
      healthcare expenditures are required to enhance the acquisition of better
      hospital resources that may improve healthcare. This study presents an overview
      of healthcare expenditures and health outcomes (i.e. infant mortality, under-5
      mortality and life expectancy) from 1995 to 2014 in Ghana. Infant and under-5
      mortalities have declined by 50 and 25%, respectively, as of 2014, while life
      expectancy has increased from 60.7 to 64.8 years. Private spending on health,
      especially out-of-pocket payments, declined but is higher than the World Health
      Organization's recommended financial threshold. Non-communicable diseases (NCDs)
      are rising with healthcare costs leading to catastrophically high healthcare
      expenditures in the future. While government's investments on healthcare have
      yielded positive results, the improvement in the health outcomes cannot be
      attributed to increased health expenditure alone. Therefore, this paper outlines
      policies on maternal health, national health insurance and healthcare reforms
      that have influenced health outcomes. In parallel, the paper highlights
      challenges of the Ghana health system of which the major ones are (1) inadequate
      financial investments in health and (2) limited health workforce and facilities.
      These challenges can be ameliorated by (1) establishing new health institutions
      and expanding existed ones; (2) providing incentives to discourage the exodus of
      health workers; (3) introduction of the concept of predictive, preventive and
      personalized medicine (PPPM) for treating NCDs; and (4) alternative insurance
      schemes for vulnerable groups. This, coupled with the will of the government to
      curb misappropriation of funds, will be important to achieving better health
      outcomes.

PMID- 29021831
TI  - Current patterns of collaboration in published neurology research: Author
      collaboration in neurological research.

PMID- 29021829
TI  - Review article: effects of type 2 diabetes therapies on bone metabolism.
AB  - Diabetes complications and osteoporotic fractures are two of the most important
      causes of morbidity and mortality in older patients, and they share many
      features, including genetic susceptibility, molecular mechanisms, and
      environmental factors. Type 2 diabetes mellitus (T2DM) compromises bone
      microarchitecture by inducing abnormal bone cell function and matrix structure
      with increased osteoblast apoptosis, diminished osteoblast differentiation, and
      enhanced osteoclast-mediated bone resorption. The linkage between these two
      chronic diseases creates a possibility that certain antidiabetic therapies may
      affect bone function. The treatment of T2DM has been improved in the past two
      decades with the development of new therapeutic drugs. Each class has a
      pathophysiologic target related to the regulation of the energy metabolism and
      insulin secretion. However, both glycemic homeostasis and bone homeostasis are
      under the control of common regulatory factors. This background allows the
      individual pharmacological targets of antidiabetic therapies to affect bone
      quality due to their indirect effects on bone cell differentiation and the bone
      remodeling process. With a greater number of diabetic patients and antidiabetic
      agents being launched, it is critical to highlight the consequences of this
      disease and its pharmacological agents on bone health and fracture risk.
      Currently, there is little scientific knowledge approaching the impact of most
      anti-diabetic treatments on bone quality and fracture risk. Thus, this review
      aims to explore the pros and cons of the available pharmacologic treatments for
      T2DM on bone mineral density and risk fractures in humans.

PMID- 29021834
TI  - Perceived social support as a moderator between negative life events and
      depression in adolescence: implications for prediction and targeted prevention.
AB  - AIM AND BACKGROUND: The role of the perceived social support in prevention of
      depression in adolescence still remains an insufficiently explored problem. By
      integrating the results of the previous studies of moderator role of perceived
      social support between negative life events and depression in adolescence we set
      up two goals. One is to determine whether perceived social support has moderator
      role in the sample consisted of clinical, subclinical, and control respondents.
      Another goal is to identify in which group the interaction effect is significant,
      i.e. the perceived social support acts as moderator. METHODS: The sample
      consisted of 412 adolescents (61.7% female and 38.3% male) aged 13-17 years (mean
      = 15.70, SD = 1.22). We applied: Data sheet for all respondents; Mini
      International Neuropsychiatric Interview; Multidimensional Scale of Perceived
      Social Support; Adolescent Life Events Questionnaire; Centre for Epidemiological
      Depression Scale. RESULTS: We have shown that the association between levels of
      depressive symptoms and negative life events changes as the value of the
      moderator variable perceived social support changes. The finding that the
      moderating interaction effect was significant only in the subclinical group is
      particularly interesting. CONCLUSIONS: Taking into account that perceived social
      support moderates the association between negative stress events and levels of
      depression, we can propose a model for the prevention of depression, which will
      include perceived social support. However, future research with longitudinal
      design is required to verify the results.

PMID- 29021832
TI  - Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities
      for personalized psychiatry.
AB  - Personalized medicine (personalized psychiatry in a specific setting) is a new
      model towards individualized care, in which knowledge from genomics and other
      omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined
      with clinical data to guide efforts to new drug development and targeted
      prescription of the existing treatment options. In this review, we summarize
      pharmacogenomic studies in mood disorders that may lay the foundation towards
      personalized psychiatry. In addition, we have discussed the possible strategies
      to integrate data from omic pillars as a future path to personalized psychiatry.
      So far, the progress of uncovering single nucleotide polymorphisms (SNPs)
      underpinning treatment efficacy in mood disorders (e.g., SNPs associated with
      selective serotonin re-uptake inhibitors or lithium treatment response in
      patients with bipolar disorder and major depressive disorder) are encouraging,
      but not adequate. Genetic studies have pointed to a number of SNPs located at
      candidate genes that possibly influence response to; (a) antidepressants COMT,
      HTR2A, HTR1A, CNR1, SLC6A4, NPY, MAOA, IL1B, GRIK4, BDNF, GNB3, FKBP5, CYP2D6,
      CYP2C19, and ABCB1 and (b) mood stabilizers (lithium) 5-HTT, TPH, DRD1, FYN,
      INPP1, CREB1, BDNF, GSK3beta, ARNTL, TIM, DPB, NR3C1, BCR, XBP1, and CACNG2. We
      suggest three alternative and complementary strategies to implement knowledge
      gained from pharmacogenomic studies. The first strategy can be to implement
      diagnostic, therapeutic, or prognostic genetic testing based on candidate genes
      or gene products. The second alternative is an integrative analysis (systems
      genomics approach) to combine omics data obtained from the different pillars of
      omics investigation, including genomics, epigenomes, proteomics, metabolomics and
      microbiomes. The main goal of system genomics is an identification and
      understanding of biological pathways, networks, and modules underlying drug
      response. The third strategy aims to the development of multivariable diagnostic
      or prognostic algorithms (tools) combining individual's genomic information
      (polygenic score) with other predictors (e.g., omics pillars, neuroimaging, and
      clinical characteristics) to finally predict therapeutic outcomes. An integration
      of molecular science with that of traditional clinical practice is the way
      forward to drug discoveries and novel therapeutic approaches and to characterize
      psychiatric disorders leading to a better predictive, preventive, and
      personalized medicine (PPPM) in psychiatry. With future advances in the omics
      technology and methodological developments for data integration, the goal of PPPM
      in psychiatry is promising.

PMID- 29021833
TI  - What California sea lions exposed to domoic acid might teach us about autism:
      lessons for predictive and preventive medicine.
AB  - Autism spectrum disorder (ASD) shares many biological and behavioral similarities
      with the deleterious effects of domoic acid (DA) exposure. DA is produced by
      marine algae and most commonly by species of Pseudo-nitzschia. Humans and marine
      mammals can be exposed to DA when they consume whole fish or shellfish. The
      mammalian fetus is highly sensitive to the deleterious effects of DA exposure.
      Both ASD and exposures to toxic levels of DA feature repetitive behaviors,
      challenges with social interaction, and seizures. They can also share a
      commonality in brain anatomy and function, particularly the balance between
      excitatory and inhibitory mechanisms. The current article is relevant to
      predictive, preventive, and personalized medicine for three reasons. First,
      shellfish consumption may be a risk factor for ASD and the regulatory limit for
      DA should be adjusted to prevent this possibility. Human contributions to
      increased algal production of DA in coastal waters should be identified and
      reduced. Second, evaluations of sentinel species wild and free-roaming in the
      environment, though typically outside the purview of biomedical research, should
      be much more fully employed to gain insights to risk factors for human disease.
      To better identify and prevent disease, biomedical researchers should study wild
      populations. Third, studies of DA exposure highlight the possibility that
      glutamate additives to processed foods may also have deleterious impacts on human
      brain development and behavior.

PMID- 29021835
TI  - Progressive changes in hippocampal cytoarchitecture in a neurodevelopmental rat
      model of epilepsy: implications for understanding presymptomatic epileptogenesis,
      predictive diagnosis, and targeted treatments.
AB  - Epilepsies affect about 4% of the population and are frequently characterized by
      a prolonged "silent" period before the onset of spontaneous seizures. Most
      current animal models of epilepsy either involve acute seizure induction or
      kindling protocols that induce repetitive seizures. We have developed a rat model
      of epilepsy that is characterized by a slowly progressing series of behavioral
      abnormalities prior to the onset of behavioral seizures. In the current study, we
      further describe an accompanying progression of cytoarchitectural changes in the
      hippocampal formation. Groups of male and female SD rats received serial
      injections of a low dose of domoic acid (0.020 mg/kg) (or vehicle) throughout the
      second week of life. Postmortem hippocampal tissue was obtained on postnatal days
      29, 64, and 90 and processed for glial fibrillary acidic protein (GFAP), NeuN,
      and calbindin expression. The data revealed no significant changes on postnatal
      day (PND) 29 but a significant increase in hilar NeuN-positive cells in some
      regions on PND 64 and 90 that were identified as ectopic granule cells. Further,
      an increase in GFAP positive cell counts and evidence of reactive astrogliosis
      was found on PND 90 but not at earlier time points. We conclude that changes in
      cellular expression, possibly due to on-going non-convulsive seizures, develop
      slowly in this model and may contribute to progressive brain dysfunction that
      culminates in a seizure-prone phenotype.

PMID- 29021836
TI  - Specific protein biomarker patterns for Alzheimer's disease: improved diagnostics
      in progress.
AB  - This short review looks at Alzheimer's disease (AD) diagnosis through my own
      point of view, going from imaging through cerebrospinal fluid to blood proteins.
      Over the last couple of years, we have published two papers targeted at
      Alzheimer's diagnosis. In one paper, we took an approach of selecting a specific
      target, namely, activity-dependent neuroprotective protein (ADNP), and our
      results tightened the association of ADNP blood expression with intelligence. In
      another paper, we took an unbiased approach of analysis of all genes expressed in
      lymphoblastoid cells lines and discovered changes in expression of the regulator
      of G-protein signaling 2 (RGS2) as a potential AD predictor. This review will
      assess our data in comparison to selected independent studies focusing on blood
      protein biomarkers as well as assessing saliva and urine samples with potential
      predictive value for AD. Furthermore, the review will provide directions for a
      combination of innovative markers, stratifying the population toward disease
      prevention and personalized medicine.

PMID- 29021838
TI  - Qualitative analysis of Parkinson's disease information on social media: the case
      of YouTubeTM.
AB  - INTRODUCTION: There is a paucity of data pertaining to the usefulness of
      information presented on social media platforms on chronic neuropsychiatric
      conditions such as Parkinson's disease (PD). The aim of this study was to examine
      the quality of YouTubeTM videos that deliver general information on PD and the
      availability and design of instructional videos addressing the caregiving role in
      PD. METHODS: YouTubeTM was searched using the keyword "Parkinson's disease" for
      relevant videos. Videos were assessed for usefulness and accuracy based on pre
      defined criteria. Data on video characteristics including total viewership,
      duration, ratings, and source of videos were collated. Instructional PD videos
      that addressed the role of caregivers were examined closely for the design and
      scope of instructional content. RESULTS: A total of 100 videos met the inclusion
      criteria. Just under a third of videos (28%) was uploaded by trusted academic
      organisations. Overall, 15% of PD videos were found to be somewhat useful and
      only 4% were assessed as providing very useful PD information; 3% of surveyed
      videos were misleading. The mean number of video views (regardless of video
      source) was not significantly different between the different video ratings (p =
      0.86). Although personal videos trended towards being less useful than videos
      from academic organisations, this association was not statistically significant
      (p = 0.13). CONCLUSION: To our knowledge, this is the first study to assess the
      usefulness of PD information on the largest video-sharing website, YouTubeTM. In
      general, the overall quality of information presented in the videos screened was
      mediocre. Viewership of accurate vs. misleading information was, however, very
      similar. Therefore, healthcare providers should direct PD patients and their
      families to the resources that provide reliable and accurate information.

PMID- 29021837
TI  - The BSSG rat model of Parkinson's disease: progressing towards a valid,
      predictive model of disease.
AB  - ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder, classically
      considered a movement disorder. A great deal is known about the anatomical
      connections and neuropathology and pharmacological changes of PD, as they relate
      to the loss of dopaminergic function and the appearance of cardinal motor
      symptoms. Our understanding of the role of dopamine in PD has led to the
      development of effective pharmacological treatments of the motor symptoms in the
      form of dopamine replacement therapy using levodopa and dopaminergic agonists.
      Much of the information concerning these drug treatments has been obtained using
      classical neurotoxic models that mimic dopamine depletion (e.g., 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine or MPTP, 6-hydroxydopamine, reserpine).
      However, PD is more than a disorder of the nigrostriatal dopamine pathway. Our
      understanding of the neuropathology of PD has undergone massive changes, with the
      discovery that mutations in alpha-synuclein cause a familial form of PD and that
      PD pathology may spread, affecting multiple neurotransmitter systems and brain
      regions. These new developments in our understanding of PD demand that we
      reconsider our animal models. While classic neurotoxin models have been useful
      for the development of effective symptomatic treatments for motor manifestations,
      the paucity of a valid animal model exhibiting the progressive development of
      multiple key features of PD pathophysiology and phenotype has impeded the search
      for neuroprotective therapies, capable of slowing or halting disease progression.
      RELEVANCE OF THE ARTICLE FOR PREDICTIVE PREVENTIVE AND PERSONALISED MEDICINE:
      What characteristics would a good animal model of human PD have? In so much as is
      possible, a good model would exhibit as many behavioral, anatomical, biochemical,
      immunological, and pathological changes as are observed in the human condition,
      developing progressively, with clear, identifiable biomarkers along the way.
      Here, we review the BSSG rat model of PD, a novel environmental model of PD, with
      strong construct, face, and predictive validity. This model offers an effective
      tool for the screening of preventive therapies that may prove to be more
      predictive of their effects in human patients.

PMID- 29021839
TI  - Diffusion tensor imaging for multilevel assessment of the visual pathway:
      possibilities for personalized outcome prediction in autoimmune disorders of the
      central nervous system.
AB  - The afferent visual pathway represents the most frequently affected white matter
      pathway in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders
      (NMOSD). Diffusion tensor imaging (DTI) can reveal microstructural or non-overt
      brain tissue damage and quantify pathological processes. DTI facilitates the
      reconstruction of major white matter fiber tracts allowing for the assessment of
      structure-function and damage-dysfunction relationships. In this review, we
      outline DTI studies investigating the afferent visual pathway in idiopathic optic
      neuritis (ON), NMOSD, and MS. Since MS damage patterns are believed to depend on
      multiple factors, i.e., ON (anterior visual pathway damage), inflammatory lesions
      (posterior visual pathway damage), and global diffuse inflammatory and
      neurodegenerative processes, comprehensive knowledge on different contributing
      factors using DTI in vivo may advance our understanding of MS disease pathology.
      Combination of DTI measures and visual outcome parameters yields the potential to
      improve routine clinical diagnostic procedures and may further the accuracy of
      individual prognosis with regard to visual function and personalized disease
      outcome. However, due to the inherent limitations of DTI acquisition and post
      processing techniques and the so far heterogeneous and equivocal data of previous
      studies, evaluation of the true potential of DTI as a possible biomarker for
      afferent visual pathway dysfunction is still substantially limited. Further
      research efforts with larger longitudinal studies and standardized DTI
      acquisition and post-processing validation criteria are needed to overcome
      current DTI limitations. DTI evaluation at different levels of the visual pathway
      has the potential to provide markers for individual damage evaluation in the
      future. As an imaging biomarker, DTI may support individual outcome prediction
      during personalized treatment algorithms in MS and other neuroinflammatory
      diseases, hereby leveraging the concept of predictive, preventive, and
      personalized medicine in the field of clinical neuroimmunology.

PMID- 29021840
TI  - Vaccination and autoimmune diseases: is prevention of adverse health effects on
      the horizon?
AB  - Autoimmune diseases, including multiple sclerosis and type 1 diabetes mellitus,
      affect about 5% of the worldwide population. In the last decade, reports have
      accumulated on various autoimmune disorders, such as idiopathic thrombocytopenia
      purpura, myopericarditis, primary ovarian failure, and systemic lupus
      erythematosus (SLE), following vaccination. In this review, we discuss the
      possible underlying mechanisms of autoimmune reactions following vaccinations and
      review cases of autoimmune diseases that have been correlated with vaccination.
      Molecular mimicry and bystander activation are reported as possible mechanisms by
      which vaccines can cause autoimmune reactions. The individuals who might be
      susceptible to develop these reactions could be especially not only those with
      previous post-vaccination phenomena and those with allergies but also in
      individuals who are prone to develop autoimmune diseases, such as those with a
      family history of autoimmunity or with known autoantibodies, and the genetic
      predisposed individuals. Further research is encouraged into the direct
      associations between vaccines and autoimmune conditions, and the biological
      mechanisms behind them.

PMID- 29021842
TI  - Cardiac resynchronization therapy in ischemic and non-ischemic cardiomyopathy.
AB  - Cardiac resynchronization therapy (CRT) using a biventricular pacing system has
      been an effective therapeutic strategy in patients with symptomatic heart failure
      with a reduced left ventricular ejection fraction (LVEF) of 35% or less and a QRS
      duration of 130 ms or more. The etiology of heart failure can be classified as
      either ischemic or non-ischemic cardiomyopathy. Ischemic etiology of patients
      receiving CRT is prevalent predominantly in North America, moderately in Europe,
      and less so in Japan. CRT reduces mortality similarly in both ischemic and non
      ischemic cardiomyopathy, whereas reverse structural left ventricular remodeling
      occurs more favorably in non-ischemic cardiomyopathy. Because the substrate for
      ventricular arrhythmias appears to be more severe in cases of ischemic as
      compared with non-ischemic cardiomyopathy, the use of an implantable cardioverter
      defibrillator (ICD) backup method could prolong the long-term survival,
      especially of patients with ischemic cardiomyopathy, even in the presence of CRT.
      The aim of this review article is to summarize the effects of CRT on outcomes and
      the role of ICD backup in ischemic and non-ischemic cardiomyopathy.

PMID- 29021843
TI  - Impact of baseline renal function on all-cause mortality in patients who
      underwent cardiac resynchronization therapy: A systematic review and meta
      analysis.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) improves both morbidity and
      mortality in selected patients with heart failure and increased QRS duration.
      However, chronic kidney disease (CKD) may have an adverse effect on patient
      outcome. The aim of this systematic review was to analyze the existing data
      regarding the impact of baseline renal function on all-cause mortality in
      patients who underwent CRT. METHODS: Medline database was searched
      systematically, and studies evaluating the effect of baseline renal function on
      all-cause mortality in patients who underwent CRT were retrieved. We performed
      three separate analyses according to the comparison groups included in each
      study. Data were analyzed using Review Manager software (RevMan version 5.3;
      Oxford, UK). RESULTS: We included 16 relevant studies in our analysis.
      Specifically, 13 studies showed a statistically significant higher risk of all
      cause mortality in patients with impaired baseline renal function who underwent
      CRT. The remaining three studies did not show a statistically significant result.
      The quantitative synthesis of five studies showed a 19% decrease in all-cause
      mortality per 10-unit increment in estimated glomerular filtration rate (eGFR)
      [HR: 0.81, 95% CI (0.73-0.90), p<0.01, 86% I2]. Additionally, we demonstrated
      that patients with an eGFR<60 mL/min/1.73 m2 had an all-cause mortality rate of
      66% [HR: 1.66, 95% CI (1.37-2.02), p<0.01, 0% I2], which was higher than in those
      with an eGFR>=60 mL/min/1.73 m2. CONCLUSION: Baseline renal dysfunction has an
      adverse effect on-all cause mortality in patients who underwent CRT.

PMID- 29021844
TI  - Intracoronary acetylcholine application as a possible probe inducing J waves in
      patients with early repolarization syndrome.
AB  - Acetylcholine is widely used for a diagnostic provocation test of coronary spasm
      in patients with vasospastic angina. Acetylcholine usually induces coronary
      vasodilatation mediated by muscarinic receptor activation, but sometimes it
      evokes vasoconstriction of coronary arteries where the endothelium is damaged.
      Early repolarization syndrome is characterized by a J wave observed at the end of
      the QRS complex in a surface electrocardiogram. The J wave is attributed to the
      transmural voltage gradient at the early repolarization phase across the
      ventricular wall, which stems mainly from prominent transient outward current in
      the epicardium, but not in the endocardium. Transient high-dose application of
      acetylcholine into the epicardial coronary arteries provides a unique opportunity
      to augment net outward current, selectively, in the ventricular epicardium and
      unmask the J wave, irrespective of the cardiac ischemia based on coronary spasm.
      Acetylcholine augments cardiac membrane potassium conductance by enhancing
      acetylcholine-activated potassium current directly and by activating adenosine
      triphosphate-sensitive potassium current, in addition to the reduced sodium and
      calcium currents in the setting of severe ischemia due to vasospasm. However, the
      role of acetylcholine as an arrhythmogenic probe of the J wave induction in
      patients with suspected early repolarization syndrome warrants future prospective
      study.

PMID- 29021845
TI  - Incidence and predictors of pericardial effusion as an early complication of
      catheter ablation for atrial fibrillation: The Japanese Catheter Ablation
      Registry of Atrial Fibrillation (J-CARAF).
AB  - BACKGROUND: Pericardial effusion (PE) is one of the most frequent complications
      from catheter ablation of atrial fibrillation (AF). We assessed the prevalence
      and predictive factors of PE that require invasive treatment as an early
      complication of AF ablation. METHODS: The Japanese Heart Rhythm Society requested
      electrophysiology centers to register the relevant data of patients who underwent
      AF ablation during 6 months from 2011 to 2015. We compared the clinical profiles
      and the procedures of AF ablation between patients who had ablation-related PE
      and those who did not. RESULTS: Two-hundred-and-eight institutions reported the
      data of 8319 AF ablation sessions (age 63.4+/-10.7 years). A total of 414
      complications occurred in 401 patients (4.8%). The incidence of invasively
      treated critical PE was 1.0% (n=85) of total procedures, while conservatively
      treated noncritical PE appeared in 95 subjects. When clinical and procedural
      variables were compared between patients who suffered critical PE and 8140 PE
      free patients, deep sedation (p=0.030), impaired left ventricular function
      (p=0.031), and periprocedural warfarin (p=0.023) significantly increased the
      incidence of critical PE in univariate analysis. Use of 3-D imaging system
      (p<0.001) and a periprocedural direct oral anticoagulant (DOAC, p=0.002) were
      related with lower incidence of critical PE. Among these factors, multivariate
      logistic regression analysis showed that 3-D imaging system (odds ratio 0.23 [95%
      CI: 0.14-0.39], p<0.001) and a periprocedural DOAC (odds ratio 0.49 [95% CI: 0.27
      0.90], p=0.020) are independent predictors of the lower incidence of PE.
      CONCLUSIONS: Critical PE occurred in 1% of AF ablation procedures in Japan. Our
      results suggest that 3-D imaging system use independently reduces the frequency
      of PE. DOACs in the setting of catheter ablation of AF seemed to be non-inferior
      to warfarin in terms of safety and effectiveness.

PMID- 29021846
TI  - The influence of residual apixaban on bleeding complications during and after
      catheter ablation of atrial fibrillation.
AB  - BACKGROUND: The periprocedural protocol for atrial fibrillation (AF) ablation
      commonly includes anticoagulation therapy. Apixaban, a direct oral anticoagulant,
      is currently approved for clinical use; however, little is known about the
      effects of residual apixaban concentration on bleeding complications during/after
      AF ablation. Therefore, we measured residual apixaban concentration by using mass
      spectrometry and examined the anticoagulant's residual effects on bleeding
      complications. METHODS: Fifty-eight patients (Mean age of 64.7+/-12.5 years; 31
      males, 27 females) were enrolled and administered apixaban twice daily. We
      analyzed trough apixaban concentration, activated clotting time (ACT), heparin
      dose, and bleeding complications during/after AF ablation. Apixaban
      concentrations were directly measured using mass spectrometry. RESULTS: Bleeding
      complications were observed in 19 patients (delayed hemostasis at the puncture
      site, 16; hematuria, 3; hemosputum, 1). No patient required blood transfusion.
      The mean trough apixaban concentration was significantly lower in patients with
      bleeding complications than without (152.4+/-73.1 vs. 206.8+/-98.8 ng/mL
      respectively, P=0.037), while the heparin dose to achieve ACT>300 s was
      significantly higher in patients with bleeding complications (9368.4+/-2929.0 vs.
      7987.2+/-2135.2 U/body respectively, P=0.046). Interestingly, a negative
      correlation was found between the trough apixaban concentration and the heparin
      dose to achieve ACT>300 s (P=0.033, R=-0.281). CONCLUSIONS: Low residual plasma
      apixaban is associated with a higher incidence of bleeding complications
      during/after AF ablation, potentially because of a greater heparin requirement
      during AF ablation.

PMID- 29021849
TI  - Feasibility, safety, and potential demand of emergent brain magnetic resonance
      imaging of patients with cardiac implantable electronic devices.
AB  - BACKGROUND: The feasibility, safety, and potential demand of emergent magnetic
      resonance imaging (MRI) of patients with a cardiac implantable electronic device
      (CIED) in emergency situations are unknown. METHODS: We retrospectively compared
      emergent and scheduled MRI orders for patients with CIEDs at Kameda General
      Hospital, a tertiary hospital in Japan, from October 2012 to September 2016.
      RESULTS: We identified 11 emergent MRI orders via the emergency room and 38
      scheduled MRI orders. Although the baseline characteristics were similar between
      the two groups, brain scanning was predominant in emergent scanning (p=0.002).
      The reasons for MRI and physicians who ordered it were also significantly
      different between the two groups (p<0.001, p=0.03, respectively). Among the
      emergent orders via the emergency room, 10 out of 11 were brain scans. Nine out
      of 10 patients underwent successful emergent brain MRI. The time from arrival at
      the emergency room to MRI was 144+/-29 min, and the time from the MRI order made
      by the cardiologist to its actual performance was 60+/-10 min. Four out of 9
      patients had a diagnosis of acute stroke confirmed by emergent MRI, and two had
      emergent thrombolysis with a complete neurological recovery. All emergent
      scanning was conducted safely with no complications. CONCLUSIONS: Our study found
      the potential demand of brain MRI of patients with CIEDs in emergency situations
      compared with scheduled scanning, which was shown to be feasible and safe for the
      diagnosis and treatment of an acute stroke.

PMID- 29021847
TI  - A new mapping method to estimate exit sites of ventricular arrhythmias using
      intracardiac echocardiography and M-mode for catheter ablation.
AB  - BACKGROUND: Catheter ablation of premature ventricular complexes (PVCs) has been
      used as a curative therapy in many cases. Intracardiac ultrasound with a magnetic
      sensor probe has recently become available for catheter ablation. In this study,
      we assessed a new mapping method, contraction mapping, for determining the
      optimal ablation sites using intracardiac ultrasound and M-mode. This study
      sought to assess the accuracy of the new mapping method using intracardiac
      echocardiography. METHODS: Eighteen patients (10 males and eight females; mean
      age, 63+/-12 years) with 104 mapping points diagnosed as idiopathic PVCs were
      included in this study. At the mapping points, the time interval from the onset
      of the QRS to the onset of the contraction (QRS-c-time) and the local activation
      time were measured using M-mode with an intracardiac echo probe and using the
      conventional method. The correlation between the QRS-c-time and local activation
      time were studied. RESULTS: The QRS-c-time was significantly correlated with the
      local activation time (activation time=-66.8+0.882 * QRS-c-time, R2=0.728,
      p<0.0001). CONCLUSIONS: Contraction mapping could help determine the local
      activation time without the delivery of a catheter to the mapping points.

PMID- 29021848
TI  - Scar characteristics derived from two- and three-dimensional reconstructions of
      cardiac contrast-enhanced magnetic resonance images: Relationship to ventricular
      tachycardia inducibility and ablation success.
AB  - BACKGROUND: The relationship between cardiac contrast-enhanced magnetic resonance
      imaging (CE-MRI)-derived scar characteristics and substrate for ventricular
      tachycardia (VT) in patients with structural heart disease (SHD) has not been
      fully investigated. METHODS: This study included 51 patients (mean age, 63.3+/
      15.1 years) who underwent CE-MRI with SHD and VT induction testing before
      ablation. Late gadolinium-enhanced (LGE) regions on MRI slices were quantified by
      thresholding techniques. Signal intensities (SIs) 2-6 SDs above the mean SI of
      the remote left ventricular (LV) myocardium were considered as scar border zones,
      and SI>6 SDs, as scar zone, and the scar characteristics related to VT
      inducibility and successful ablation via endocardial approaches were evaluated.
      RESULTS: The proportion of the total CE-MRI-derived scar border zone in the
      inducible VT group was significantly greater than that in the non-inducible VT
      group (26.3+/-9.9% vs. 19.2+/-7.8%, respectively, P=0.0323). The LV endocardial
      scar zone to total LV myocardial scar zone ratio in patients whose ablation was
      successful was significantly greater than that in those whose ablation was
      unsuccessful (0.61+/-0.11 vs. 0.48+/-0.12, respectively, P=0.0042). Most
      successful ablation sites were located adjacent to CE-MRI-derived scar border
      zones. CONCLUSIONS: By CE-MRI, we were able to characterize not only the scar,
      but also its location and heterogeneity, and those features seemed to be related
      to VT inducibility and successful ablation from an endocardial site.

PMID- 29021850
TI  - Long-term survival of implantable cardioverter defibrillator recipients with end
      stage renal disease.
AB  - BACKGROUND: The efficacy of implantable cardioverter-defibrillators (ICD) for
      primary prevention of sudden cardiac death (SCD) has not been studied in patients
      with end-stage renal disease (ESRD) and left ventricular dysfunction. We sought
      to identify predictors of long-term survival among ICD recipients with and
      without ESRD. METHODS: Patients implanted with an ICD at our institution from
      January 2006 to March 2014 were retrospectively identified. Clinical and
      demographic characteristics were collected. Patients were stratified by the
      presence of ESRD at the time of ICD implant. Mortality data were collected from
      the Social Security Death Index (SSDI). RESULTS: A total of 3453 patients
      received an ICD at our institution in the pre-specified time period, 184 (5.3%)
      of whom had ESRD. In general, ESRD patients were sicker and had more
      comorbidities. Kaplan Meier survival curve showed that ESRD patients had worse
      survival as compared with non-dialysis patients (p<0.001). Following adjustment
      for differences in baseline characteristics, patients with ESRD remained at
      increased long-term mortality in the Cox model. The one-year mortality in the
      ESRD patients was 18.1%, as compared with 7.7% in the non-dialysis cohort
      (p<0.001). The three-year mortality in ESRD patients was 43%, as compared with
      21% in the non-dialysis cohort (p<0.001). CONCLUSION: ESRD patients are at
      significantly increased risk of mortality as compared with a non-dialysis cohort.
      While the majority of these patients survive more than one year post-diagnosis,
      the three-year mortality is high (43%). Randomized studies addressing the
      benefits of ICDs in ESRD patients are needed to better define their value for
      primary prevention of SCD.

PMID- 29021851
TI  - Cardiac troponin T as a predictor of cardiac death in patients with left
      ventricular dysfunction.
AB  - BACKGROUND: Cardiac troponin T (cTnT) has been reported to be associated with
      cardiac mortality. In the present study, we evaluated the role of routine
      assessment of cTnT as a predictor of future cardiac death in patients with left
      ventricular (LV) dysfunction. METHODS: Patients who were eligible for
      prophylactic implantable cardioverter defibrillator (ICD) were included from
      cardiac catheterization database. Inclusion criteria were patients with LV
      ejection fraction of <= 35% and with New York Heart Association (NYHA) >=class
      II. Exclusion criteria were patients with acute coronary syndrome, ICD for
      secondary prevention, NYHA class IV, and lack of data. The final study patients
      were divided into the following three groups in accordance with two quartile
      points of serum cTnT levels: low cTnT, intermediate cTnT, and high cTnT groups.
      The primary endpoint of this study was cardiac death. RESULTS: A total of 70
      patients were included (mean age, 62+/-13 years; male individuals, 56; ischemic,
      36; and non-ischemic, 34). During the observation period of 2.2 years, cardiac
      death was observed in 17 patients (fatal arrhythmic event, 9; heart failure, 7;
      myocardial infarction, 1). In the Kaplan-Meier analysis, the high cTnT group
      showed the highest risk among all the groups (p<0.001). Even in sub-analyses for
      ischemic and non-ischemic patients, the results were the same, and the high cTnT
      group showed the highest event rate (p<0.05). In contrast, no cardiac death was
      observed in the low cTnT group. CONCLUSION: The cTnT levels in a stable state
      were associated with cardiac death in patients with LV dysfunction, even in those
      with non-ischemic diseases.

PMID- 29021852
TI  - Association between serum soluble urokinase-type plasminogen activator receptor
      and atrial fibrillation.
AB  - BACKGROUND: Circulating soluble urokinase-type plasminogen activator receptor
      (suPAR), which can reflect immune activation and low-grade inflammation, may be a
      novel biomarker of cardiovascular disease. METHODS: We investigated the potential
      association between suPAR and the prevalence of atrial fibrillation (AF) by
      analyzing patients with either sinus rhythm, paroxysmal atrial fibrillation
      (PAF), or non-paroxysmal atrial fibrillation (NPAF), which indicates either
      permanent or persistent AF. RESULTS: Among 426 patients enrolled (mean age 71.4+/
      9.2 years; 110 (25.8%) female), 310, 62, and 54 were diagnosed with sinus rhythm,
      PAF, and NPAF, respectively. NPAF was >10-fold more prevalent in the highest
      suPAR quartile (>3534 pg/mL; 32 (30.2%) of 106 patients) than in the lowest suPAR
      quartile (<1802 pg/mL; 3 (2.8%) of 107 patients). Logistic regression analysis
      showed that, as compared with the lowest suPAR quartile, the highest suPAR
      quartile was associated with NPAF with an odds ratio of 6.48 (95% confidence
      interval, 1.71-24.5) after adjustment for sex, age, log(eGFR), C-reactive
      protein, and systolic blood pressure. In multivariate receiver operating
      characteristic analysis to predict NPAF, the area under the curve (AUC) for the
      combination of age, sex, log(eGFR), and C-reactive protein was 0.777 (standard
      error [SE], 0.036); the addition of log(suPAR) slightly improved the prediction
      (AUC, 0.812; SE, 0.034, P=0.084). CONCLUSIONS: Serum suPAR was associated with
      AF, particularly NPAF, as demonstrated by multivariate logistic regression
      analysis. Whether suPAR promotes or maintains AF should be investigated in
      further studies.

PMID- 29021853
TI  - Indications for suboptimal low-dose direct oral anticoagulants for non-valvular
      atrial fibrillation patients.
AB  - BACKGROUND: Direct oral anticoagulants (DOACs) have been developed for stroke
      prevention in patients with non-valvular atrial fibrillation (NVAF). We conducted
      a retrospective cohort study of patients with NVAF who were newly treated with
      DOACs in a real-world clinical setting. METHODS: We retrospectively analyzed
      patients with NVAF newly treated with one of three DOACs-dabigatran, rivaroxaban,
      or apixaban-between January 1, 2013, and December 31, 2015. RESULTS: A total of
      670 patients with NVAF who were newly prescribed one of the three DOACs were
      analyzed; 74 patients (10.9%) received dabigatran, 290 (43.3%) received
      rivaroxaban, and 306 (45.8%) received apixaban. Fifteen patients had
      thromboembolic events, almost half of which were due to discontinuation of DOACs.
      Six patients had major bleeding, although almost all were discharged with good
      neurological prognoses. A total of 129 patients were treated with a suboptimal
      low-dose DOAC; none experienced a thromboembolic event as long as the DOAC was
      taken regularly, and none of the patients in any of the three DOAC groups had
      major bleeding events. CONCLUSIONS: With good adherence, the clinical course
      associated with DOACs is comparatively good. In the future, suboptimal low-dose
      DOAC therapy may serve as an appropriate choice for some patients with a high
      risk of stroke and bleeding.

PMID- 29021854
TI  - Left atrial remodeling: Regional differences between paroxysmal and persistent
      atrial fibrillation.
AB  - BACKGROUND: The mechanisms underlying self-perpetuation of persistent atrial
      fibrillation (AF) are not well understood. To gain insight into these mechanisms,
      we conducted a study comparing left atrial (LA) electroanatomic maps obtained
      during sinus rhythm between patients with paroxysmal AF (PAF) and patients with
      persistent AF (PerAF). METHODS: The study included 23 men with PAF (age, 56.3+/
      12.1 years) and 13 men with PerAF (age, 54.3+/-13.4 years). LA voltage mapping
      was performed during sinus rhythm. The clinical and electroanatomic
      characteristics of the two groups were evaluated and analyzed statistically.
      RESULTS: The bipolar voltages at the LA septum, roof, and posterior wall, right
      superior pulmonary vein (PV) and its antrum, right superior PV carina, and right
      inferior PV antrum were significantly lower in patients with PerAF than in those
      with PAF. The bipolar voltages in other parts of the LA did not differ
      statistically between the two groups. CONCLUSION: PAF and PerAF seem to be
      characterized by differences in the regional voltage in the LA and PVs. The LA
      structural remodeling of PerAF may initiate from the right PVs and their antra
      and LA septum, roof, and posterior wall.

PMID- 29021856
TI  - Refractory ventricular tachycardia caused by inflow cannula mechanical injury in
      a patient with left ventricular assist device: Catheter ablation and pathological
      findings.
AB  - In patients with left ventricular assist device (LVAD), a minority of post
      operative ventricular tachycardias (VTs) is caused by contact between the inflow
      cannula and the endocardium. Currently, electrophysiologic characteristics and
      pathologic features of this condition are lacking. We report on a case of a
      successfully ablated mechanical VT. After VT recurrence, heart transplantation
      took place. Pathologic observations were consistent with direct tissue injury and
      inflammation, eventually contributing to persisting arrhythmias. Radiofrequency
      catheter ablation can be a safe and effective option to treat arrhythmias caused
      by inflow cannula interference in the short term, although a high recurrence rate
      is expected.

PMID- 29021855
TI  - CHADS2 and modified CHA2DS2-VASc scores for the prediction of congestive heart
      failure in patients with nonvalvular atrial fibrillation.
AB  - BACKGROUND & PURPOSE: We have conducted a retrospective observational study to
      analyze the correlation between the CHADS2 score, the modified CHA2DS2-VASc
      (mCHA2DS2-VASc) score, and the incidence of all-cause death and congestive heart
      failure (CHF). METHODS: The study cohort consisted of 292 consecutive patients
      with nonvalvular atrial fibrillation (NVAF) admitted to our hospital from 2012 to
      2014. Electronic medical records were used to confirm medical history including
      prior heart failure, hypertension, diabetes, stroke, and coronary disease. A
      follow-up survey for all-cause deaths and incidence of CHF was carried out from
      the baseline data to May 2015. We analyzed the correlation between each score and
      the endpoints using the Kaplan-Meier method and the Cox proportional hazards
      model. RESULT: During the follow up period (mean=1.6 years), 69 all-cause deaths
      and 58 CHF events occurred in the cohort. There was no significant association
      between these scores and all-cause death in our CHF cohort. The incidence of CHF
      significantly increased along with increased CHADS2 (p=0.018) or mCHA2DS2-VASc
      scores (p=0.044). The hazard ratio (HR) for CHF after adjustment for drug
      treatment was obtained from a Cox proportional hazards model. The HRs for the
      CHADS2 and mCHA2DS2-VASc scores were 1.38 (95% CI; 1.13-1.68) and 1.35 (95% CI;
      1.24-1.59), respectively. CONCLUSION: Calculation of the CHADS2 and mCHA2DS2-VASc
      scores in order to evaluate the risk of systemic thromboembolism was useful to
      predict the onset of CHF, but not all-cause death, in patients with NVAF.

PMID- 29021857
TI  - Arrhythmogenic left atrial roof vein.
AB  - A seventy year-old male was referred to our hospital to undergo radiofrequency
      catheter ablation (RFCA) for drug-refractory paroxysmal atrial fibrillation (AF).
      Pre-operative three-dimensional computed tomography revealed a unique left atrial
      (LA) roof vein. Electrophysiological findings showed expansion of the myocardial
      sleeve and local firing in the LA roof vein. We performed isolation of this
      arrhythmogenic abnormal vein concomitant with general pulmonary vein isolation in
      this case, and AF did not recur after the procedure.

PMID- 29021858
TI  - Landiolol suppression of electrical storm of torsades de pointes in patients with
      congenital long-QT syndrome type 2 and myocardial ischemia.
AB  - A 76-year-old man who had been diagnosed with long-QT syndrome type 2 had
      frequent syncopal attacks. The electrocardiogram was monitored, and frequent
      torsades de pointes (TdP) was detected despite administration of conventional
      medications: oral propranolol, verapamil, intravenous magnesium sulfate,
      verapamil, and lidocaine. In contrast, 2 MUg/kg/min landiolol could completely
      suppress TdP. Subsequently, an implantable cardioverter defibrillator was placed,
      and he was diagnosed with silent myocardial ischemia using myocardial perfusion
      scintigraphy and coronary angiography. This is the first case report wherein
      landiolol effectively suppressed TdP due to long-QT syndrome with silent
      myocardial ischemia.

PMID- 29021859
TI  - The electrical circuit of a hemodynamically unstable and recurrent ventricular
      tachycardia diagnosed in 35 s with the Rhythmia mapping system.
AB  - Herein, we report a 47-year-old woman with ischemic cardiomyopathy who underwent
      ablation therapy due to an electrical storm without any triggers. The voltage
      mapping in sinus rhythm with the Rhythmia system and Orion catheter displayed
      several LAVAs in and around the anteroapical scar area. Although the patient did
      not tolerate the induced clinical ventricular tachycardia, which was
      reproductively induced, 35-second-mapping in the scar zone with the Orion
      catheter demonstrated the VT circuit with the critical isthmus. This report shows
      the possibility of the new ultra-high density mapping system in a specific
      ischemic VT patient.

PMID- 29021860
TI  - Atriofascicular Mahaim with Ebstein anomaly: A case report.
AB  - We report a case of a 7-year-old girl with atriofascicular Mahaim (AFM) pathway
      concomitant with Ebstein's anomaly. The QRS wave showed left bundle branch block
      pattern on electrocardiogram. Holter electrocardiogram showed prolongation of the
      PR interval and QRS morphological change during sinus tachycardia. An
      electrophysiological study demonstrated that the distal His potential appeared
      earlier than the proximal His potential, which suggested retrograde His
      conduction toward the atrioventricular node. Conduction from the Mahaim fiber to
      the His bundle was faster than that from the atrioventricular node towards the
      His bundle. The findings of this important case allowed a differential diagnosis
      between AFM and Wolff-Parkinson-White (WPW) syndrome.

PMID- 29021861
TI  - Three cases of vasospastic angina following catheter ablation of atrial
      fibrillation.
AB  - Pulmonary vein isolation is an effective treatment for patients with atrial
      fibrillation (AF).Although vasospastic angina (VSA) is not a common complication
      after ablation of AF, we report 3 cases of VSA following ablation of persistent
      AF. Two of the 3 patients felt chest pain following pulmonary vein isolation, and
      complex fractionated atrial electrogram ablations were performed. ST elevation in
      the inferior leads and atrioventricular block occurred because of severe coronary
      vasospasm. In the third patient, the electrocardiography monitor detected
      transient ST elevation within an hour after ablation. Treatment of VSA may be
      required following catheter ablation of AF.

PMID- 29021862
TI  - Adaptive cardiac resynchronization therapy for dilated cardiomyopathy with
      functional mitral regurgitation.
AB  - We report the case of a man in his 60s who had dilated cardiomyopathy with severe
      functional mitral regurgitation. Four years after a cardiac resynchronization
      therapy (CRT) device with an implantable cardioverter defibrillator was
      implanted, this device was replaced with an adaptive CRT device because of
      battery consumption. Seven months after replacement of this device, the left
      ventricular pacing to right ventricular activation and the atrioventricular delay
      from automatic adjustments contributed to less functional mitral regurgitation.
      The findings from our case suggest that optimal CRT, by measuring intracardiac
      conduction parameters, is effective for functional mitral regurgitation.

PMID- 29021863
TI  - Brain magnetic resonance imaging examination in a patient with non-magnetic
      resonance conditional pacemaker.
AB  - Clinical dilemmas arise when patients with a non-magnetic resonance (MR)
      conditional pacemaker are required to undergo magnetic resonance imaging (MRI).
      We encountered a pacemaker patient with debilitating non-motor symptoms of
      Parkinson's disease, who required an MRI prior to deep brain stimulation (DBS)
      surgery. MRI was performed safely without adverse events despite the presence of
      a conventional pacemaker.

PMID- 29021864
TI  - Sudden failure of ventricular pacing and recovery in a patient with cardiac
      sarcoidosis.
AB  - A 76-year-old woman with sarcoidosis who had an implantable pacemaker for
      complete atrioventricular block was admitted with syncope. Electrocardiogram
      revealed ventricular pacing failure, and a marked rise in the ventricular pacing
      threshold. 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET)
      indicated increased uptake of FDG in the ventricular septum. Three days after
      steroid therapy, the ventricular pacing threshold reverted to normal, and FDG-PET
      showed decreased FDG uptake in the ventricular septum. In this case report, we
      demonstrate that a sudden deterioration in the ventricular pacing threshold due
      to worsening cardiac sarcoidosis can be reversed with early steroid therapy.

PMID- 29021865
TI  - Minimally invasive, pericardial implantable cardioverter-defibrillator placement
      in a young child.
AB  - We report the successful minimally invasive placement of a pericardial
      implantable cardioverter-defibrillator (ICD) in a 16-kg child. A transvenous ICD
      dual coil was advanced through a small subxiphoid incision and screwed into the
      oblique sinus pericardium under fluoroscopic guidance. An additional sense-pace
      lead was sutured onto the right ventricular apex, and the generator was placed in
      the upper abdominal wall through the same incision. Threshold testing
      demonstrated successful defibrillation at 15 J. After implantation, the patient
      had two episodes of appropriate shock for ventricular fibrillation. The ICD
      system continues to show stable impedance at 6 months of follow-up.

PMID- 29021841
TI  - 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and
      surgical ablation of atrial fibrillation: Executive summary.

PMID- 29021866
TI  - Criteria for short QT interval based on a new QT-heart rate adjustment formula.
AB  - BACKGROUND: A short QT interval, within which an increased risk for atrial
      fibrillation and/or fatal cardiac arrhythmias occurs, has been difficult to
      define. METHODS: The lower percentiles of a new QTc formula were determined,
      using a precise mathematical fitting of the QT-heart rate relationship from the
      ECGs of 13,600 individuals from the NHANES II and III surveys. RESULTS: The QTc
      interval for persons in the lower fifth percentile, second (2.5th) percentile and
      first percentile, were calculated. CONCLUSIONS: Based on the new spline formula,
      a short QTc is defined at the first percentile, and is less than 380 ms in both
      men and women.

PMID- 29021867
TI  - Concealed conduction of premature ventricular complexes resulting in AV nodal
      block.
AB  - .

PMID- 29021868
TI  - Management of patients with long QT syndrome.

PMID- 29021869
TI  - A perspective of Genes and Environment for the development of environmental
      mutagen research in Asia.
AB  - Two years have passed since the Japanese Environmental Society (JEMS) made the
      official journal Genes and Environment (G&E) open access. Current subjects on
      environmental mutagen research to further advance this field are described
      herein, and the roles of JEMS and G&E are discussed. Various important subjects
      are being investigated in current research fields such as severe environmental
      pollution in Asian countries; the identification of new hazardous substances and
      elucidation of mutation mechanisms using newly developed techniques; the
      development of new genotoxicity assays including in silico predictions using
      information technology and artificial intelligence as well as bioassays.
      International exchange by scientists is important for advancing these research
      fields through international conferences such as the 12th International
      Conference and 5th Asian Congress on Environmental Mutagens and the 7th
      International Workshop on Genotoxicity Testing that will be held in 2017. G&E
      provides a common platform for high quality environmental mutagen research,
      contributes to the dissemination of Asian environmental mutagen research, and
      potentiates the level of research being conducted.

PMID- 29021870
TI  - The potential role of miRNAs in therapy of breast and ovarian cancers associated
      with BRCA1 mutation.
AB  - Germline variants within BRCA1 or BRCA2 genes account for approximately 25% of
      familial aggregations of breast-ovarian cancers. Low or no expression of BRCA1 in
      breast and ovarian cancers is associated with a good clinical response to
      treatment with platinum therapies and PARP1 inhibitors. Recent studies
      demonstrated that microRNAs - small non-coding RNAs, involved in the control of
      gene expression, can decrease BRCA1 expression by targeting the 3'UTR region of
      the gene. This article reviews reported relationships between various miRNAs,
      such as miRNA-9, miRNA-146a, miRNA-182 miRNA-218, miRNA-638 and the response to
      cytostatic drugs, mainly to platins and PARP1 inhbitors, for the treatment of
      breast and ovarian cancer associated with BRCA1 mutations.

PMID- 29021871
TI  - Knowledge on Bone Banking among Participants in an Orthopaedic Conference: A
      Preliminary Survey.
AB  - Despite increasing use of bone graft in Malaysia, there was still lack of data to
      quantify knowledge level on bone banking among orthopaedic community who are
      involved in transplantation related work. Therefore, a survey on awareness in
      tissue banking specifically bone banking, usage and choice of bone grafts was
      conducted. From 80 respondents, 82.5% were aware about tissue banking however
      only 12.5% knew of the existence of tissue banks in Malaysia. Femoral head was
      the bone allograft most often used as a substitute to autograft. Only 34.8%
      respondents preferred irradiated bone grafts whilst 46.9% preferred
      nonirradiated, indicating the need to educate the importance of radiation for
      sterilising tissues. Exhibition was the most preferred medium for awareness
      programme to disseminate information about bone banking in the orthopaedic
      community. The professional awareness is necessary to increase the knowledge on
      the use of bone graft, hence to increase bone transplantation for musculoskeletal
      surgeries in the country.

PMID- 29021872
TI  - Psychometric Properties of the Malay Language Version of Knee Injury and
      Osteoarthritis Outcome Score (KOOS) Questionnaire among Knee Osteoarthritis
      Patients: A Confirmatory Factor Analysis.
AB  - Introduction: This study aimed to cross-culturally adapt a Malay version of Knee
      Injury and Osteoarthritis Outcome Score (KOOS) and to evaluate its psychometric
      properties in patients with knee osteoarthritis (OA). Materials and Methods: The
      English version KOOS was translated into a Malay version using forward and
      backward translation process, followed by face validity and content validity. Two
      hundred and twenty-six knee OA patients attending the Outpatient and Orthopaedic
      Clinics, Universiti Sains Malaysia Hospital, completed the Malay version KOOS.
      Construct validity using confirmatory factor analysis and internal reliability
      assessment were performed. Results: The results showed that the original five
      factor model with 42 items failed to achieve acceptable values of the goodness of
      fit indices, indicating poor model fit. A new five-factor model of 26 items
      demonstrated acceptable level of goodness of fit (comparative fit index= 0.929,
      incremental fit index= 0.930, Tucker Lewis fit index= 0.920, root mean square
      error of approximation= 0.073 and Chisquared/degree of freedom= 2.183) indices to
      signify a model fit. The Cronbach's alpha value for the new model ranged from
      0.776 to 0.946. The composite reliability values of each construct ranged between
      0.819 and 0.921, indicating satisfactory to high level of convergent validity.
      Conclusion: The five-factor model with 26 items in the Malay version of KOOS
      questionnaire demonstrated a good degree of goodness of fit and was found to be
      valid, reliable and simple as an assessment tool for symptoms, pain, activity of
      daily living, sports and recreational activity and quality of life for Malaysian
      adults suffering from knee osteoarthritis.

PMID- 29021873
TI  - Comparative Study of Proximal Tibia and Iliac Crest Bone Graft Donor Sites in
      Treatment of Orthopaedic Pathologies.
AB  - Introduction: Bone graft is harvested from bone and used to stimulate bone
      healing due to its properties. The aims of the study were to compare the quantity
      of graft harvested from proximal tibia and iliac crest, and the complications at
      these donor sites. Materials and Methods: This was a prospective study carried
      out on all consecutive patients who had orthopaedic procedures that required bone
      grafting at the study centre, from April, 2015 to March, 2016. Results: During
      the study period, 86 patients were recruited; 43 of these patients had bone graft
      harvested from the proximal tibia, while the other 43 patients had graft
      harvested from the iliac crest. There were 53 males, and 33 females. Mean age of
      patients was 41.2 +/- 11 years and 40.8 +/- 16 years, for proximal tibia and
      iliac crest group respectively. Average compressed volume of graft harvested from
      proximal tibia and iliac crest were 7cm3 and 5.5cm3 respectively. Non-unions were
      the commonest indications for bone grafting, femur was the commonest bone
      requiring bone grafting. Complications such as primary haemorrhage, pain and
      surgical site infection were commoner with iliac crest than proximal tibia donor
      sites, however bone graft harvested from both proximal tibia and iliac crest
      provided adequate bone union of the indicated procedure. Conclusion: Larger
      quantity of graft can be harvested from proximal tibia than the iliac crest.
      Though graft harvested from both the proximal tibia and the iliac crest have good
      healing properties, the proximal tibia donor site gave less complication than the
      iliac crest.

PMID- 29021874
TI  - Functional Outcome of Isolated Hoffa Fractures Treated with Cannulated Cancellous
      Screw.
AB  - Introduction: Isolated Hoffa fracture is an infrequent injury and little research
      has been done on this subject. The purpose of this study was to evaluate the
      functional outcome and complications of surgically managed Hoffa fractures with
      cannulated cancellous screw. Materials and Methods: Between 2011 and 2014, eight
      isolated Hoffa fractures in seven adult patients with mean age 39.8+/-11.9 years
      (range 25-60 years) were managed with cannulated cancellous screw of 6.5mm
      diameter applied in anterior to posterior direction using swashbuckler and medial
      parapatellar approach for lateral and medial Hoffa fractures respectively. All
      patients were evaluated using knee evaluation score after two years or longer.
      Mean follow up was 28+/-3.8 months (range 24-36 months). Results: All fractures
      in the eight patients healed clinicoradiologically by the 16th week with
      excellent result in 87.5% cases and good in 12.5% cases. By the end of union, the
      range of motion (ROM) of the knee was 0 degrees  to 110 degrees  except in two
      patients. One patient had ROM 10 degrees -100 degrees  and other had 15 degrees 
      90 degrees . Mean knee evaluation score was 87.5+/-10.4. There was no incidence
      of non-union, infection or avascular changes in the patients or loss of reduction
      till final follow up. Conclusion: Open reduction and fixation with two 6.5 mm
      cannulated cancellous screws with early mobilization yielded good functional
      outcome in isolated Hoffa fractures.

PMID- 29021875
TI  - Endoprosthetic Reconstruction of distal Humerus following Resection of distal
      Humeral Giant Cell Tumours in Six Patients in Rural India.
AB  - Giant cell tumour is a commonly occurring benign bone tumour in the Indian
      population. The common sites of involvement in descending order of frequency are
      distal femur, proximal tibia, distal radius and proximal humerus. The less
      commonly occurring sites are distal humerus, pelvis and proximal femur. We
      present six cases of giant cell tumour involving the distal humerus in rural
      India. After obtaining a tissue diagnosis by Trucut biopsy and classifying using
      Enneking's classification, we proceeded to perform wide resection followed by
      endoprosthetic reconstruction using custom mega prosthesis. We present here six
      patients (M: F: 2: 4) who were managed by us between 2008-2014. They presented to
      us with pain around the elbow and restriction in range of movements. They were
      each noted radiographically to have a lytic lesion involving the distal humerus
      with the likely diagnosis of giant cell tumour. Closed biopsy was done in all of
      them to obtain a definitive diagnosis. All patients underwent wide resection and
      reconstruction using distal humerus custom prosthesis. All patients were followed
      up at 6, 12, 18 and 24 weeks and thereafter six monthly until the last review.
      They were assessed using the DASH scoring system. All patients were well with no
      evidence of recurrence with good to fair functional outcome. We conclude that
      careful pre-operative planning with meticulous soft tissue dissection and good
      implant metallurgy and design, these tumours can be treated with good long term
      functional results.

PMID- 29021876
TI  - Coracoid Process Morphology using 3D-CT Imaging in a Malaysian Population.
AB  - Introduction: The aims of this study are to define the coracoid process anatomy
      in a Malaysian population, carried out on patients in Hospital Serdang with
      specific emphasis on the dimension of the base of coracoid process which is
      important in coraco-acromial (CC) ligament reconstruction, to define the average
      amount of bone available for use in coracoid transfer, and to compare the size of
      coracoid process based on gender and race, and with findings in previous studies.
      Materials and Methods: Fifteen pairs of computed tomography (CT) based 3
      dimensional models of shoulders of patients aged between 20 to 60 years old were
      examined. The mean dimensions of coracoid were measured and compared with regards
      to gender and race. The data were also compared to previously published studies.
      Results: The mean length of the coracoid process was 37.94 +/- 4.30 mm. Male
      subjects were found to have larger-sized coracoids in all dimensions as compared
      to female subjects. The mean tip of coracoid dimension overall was 19.99 + 1.93mm
      length * 10.03 + 1.48mm height * 11.63 + 2.12mm width. The mean base of coracoid
      dimension was 18.96 + 3.71mm length * 13.84 + 1.76mm width. No significant
      differences were observed with regards to racial denomination. The overall
      coracoid size measurements were found to be smaller compared to previous studies
      done on the Western population. Conclusion: This study may suggest that
      Malaysians have smaller coracoid dimension compared to Caucasians. The findings
      further suggest that the incidence of coracoid fracture and implants pull out in
      Malaysian subjects may be higher.

PMID- 29021878
TI  - Displaced Supracondylar Humerus Fractures in Children - Are They All Identical?
AB  - Introduction: This study aims to ascertain if there are any differences in
      supracondylar fractures between children under seven years of age and those above
      7 years of age. Materials and Methods: All cases of displaced humerus
      supracondylar fractures that required surgical stabilization were identified and
      retrospectively reviewed. Demographic data, mode of injury, associated
      neurovascular injuries and details of surgery performed were obtained from
      clinical records. The Gartland classification and the extent of comminution of
      fractures were also documented from review of radiographs. Results: One hundred
      and twelve children were included in this study, of whom 61 (54.46%) were younger
      than seven years of age while 51 (45.5%) were aged seven years or older. Children
      aged seven or older had a greater incidence of associated neurological deficit at
      presentation (p=0.046). Of the six patients with nerve injury in the older age
      group, one patient (16.7%) had a radial nerve injury, two patients (33.3%) had
      ulnar nerve injuries while another two patients (33.3%) had median nerve
      injuries. There was one patient (16.7%) with both median and ulnar nerve
      injuries. Comminuted fractures were also more common in the older children
      (p=0.004). No significant differences were demonstrated between the groups with
      regard to age, gender and mechanism of injury, laterality, incidence of open
      fracture, vascular injuries and operative time. Conclusion: Children aged seven
      years or older who sustain supracondylar humeral fractures tend to get more
      comminuted fractures. There is also a higher incidence of associated neurological
      injury. These cases must be carefully examined for at presentation and parents
      need to be appropriately counselled about them.

PMID- 29021877
TI  - Determining if Positive Predictive Value using Laboratory Risk Indicator for
      Necrotising Fasciitis is Applicable in Malaysian Patients with Necrotising
      Fasciitis.
AB  - Introduction: Necrotising fasciitis (NF) is a rapidly progressive infection of
      the subcutaneous tissue and fascia which spreads rapidly. The scoring system of
      Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) developed by Wong et
      al has been proposed as a tool for distinguishing NF and other soft tissue
      infections (STI) in Singapore. We set out to establish whether the LRINEC score
      is applicable in our Malaysian setting. Materials and Methods: A cross sectional
      study of all patients admitted to our hospital diagnosed with NF or To Rule Out
      NF (TRO NF) between January 1st 2016 to 30th June 2016. The sensitivity,
      specificity, positive and negative predictive values were then calculated for
      LRINEC score of >= 6 and >= 8. Results: Fourty-four patients were identified with
      the diagnosis of NF or TRO NF in the study. Twenty-seven patients (61.4%) were
      deemed post-operatively as having NF and 17 patients (38.6%) not having NF. A
      sensitivity of 59.3% and specificity of 47.1% when a LRINEC score of >= 6 was
      taken with positive predictive value (PPV) of 64.0% and the negative predictive
      value (NPV) of 42.1%. When score >= 8 was taken, the sensitivity was 48.1% and
      specificity of 58.8% with PPV of 65% and NPV of 41.7%. Conclusion: The low
      sensitivity and low PPV achieved in this study as well as other studies makes the
      LRINEC score unsuitable to be used solely to distinguish NF with other soft
      tissue infections.

PMID- 29021881
TI  - Chronic Traumatic Sagittal Band Injury with Extensor Tendon Dislocation: Report
      of a Case and New Surgical Technique.
AB  - Chronic sagittal band injury with tendon dislocation of the extensor digitorum
      communis in the hand often requires operative stabilization. Various surgical
      techniques have been reported to repair and reconstruct the sagittal band.
      Nonetheless, most of the techniques are technically demanding and require donor
      graft. In this case report, we report a novel surgical technique to centralize
      and stabilize the tendon by reattaching the radial sagittal band with anchor
      sutures. The advantages of this new technique are simple, no donor morbidity and
      stable repair to restore the normal biomechanics of the tendon. The patient was
      able to return to work in three months and no recurrent dislocation was noted at
      review two years after surgery.

PMID- 29021879
TI  - A Comparison of Plain Radiography with Computer Tomography in Determining Coronal
      and Sagittal Alignments following Total Knee Arthroplasty.
AB  - Introduction: Optimal coronal and sagittal component positioning is important in
      achieving a successful outcome following total knee arthroplasty (TKA).
      Modalities to determine post-operative alignment include plain radiography and
      computer tomography (CT) imaging. This study aims to determine the accuracy and
      reliability of plain radiographs in measuring coronal and sagittal alignment
      following TKA. Materials and Methods: A prospective, consecutive study of 58
      patients undergoing TKA was performed comparing alignment data from plain
      radiographs and CT imaging. Hip-knee-angle (HKA), sagittal femoral angle (SFA)
      and sagittal tibial angle (STA) measurements were taken by two observers from
      plain radiographs and compared with CT alignment. Intra- and inter-observer
      correlation was calculated for each measurement. Results: Intra-observer
      correlation was excellent for HKA (r>0.89) with a mean difference of <1.9 degrees
      . The least intra-observer correlation was for SFA (mean r=0.58) with a mean
      difference of 8 degrees . Inter-observer correlation was better for HKA (r>0.95)
      and STA (r>0.8) compared to SFA (r=0.5). When comparing modalities (radiographs
      vs CT), HKA estimations for both observers showed the least maximum and mean
      differences while SFA observations were the least accurate. Conclusion:
      Radiographic estimation of HKA showed excellent intra- and inter-observer
      correlation and corresponds well with CT imaging. However, radiographic
      estimation of sagittal plane alignment was less reliably measured and correlated
      less with CT imaging. Plain radiography was found to be inferior to CT for
      estimation of biplanar prosthetic alignment following TKA.

PMID- 29021882
TI  - Primary Osteosarcoma of the Distal Fibula treated with Distal Fibulectomy with a
      Five-Year Follow-up: A Case Report.
AB  - Musculoskeletal tumours of the lower limbs especially malignant tumours are not
      common. The fibula is the site of primary bone tumours as reported in 2.4% of
      lower limb tumours with the proximal third being more frequently involved than
      the distal segment. Osteosarcoma is the most common primary malignant bone tumour
      of nonhaematopoietic origin, with distal fibular involvement in 0.47% of
      patients. The advances in imaging techniques and neo-adjuvant chemotherapy have
      now made it possible to accurately define the extent of tumour and plan limb
      salvage with tumour resection. The purpose of this case report is to highlight
      the successful outcome of limb salvage procedure with a five year follow up in an
      11-year old boy with distal fibular osteosarcoma. Limb salvage surgery with
      distal fibulectomy and retention of the foot are a good alternative to radical
      amputation.

PMID- 29021880
TI  - Use of Titanium Elastic Nails in the Adult Diaphyseal Humerus Fractures.
AB  - Introduction: Humerus shaft fractures in adults can be managed conservatively
      with functional braces or operatively with plate osteosynthesis or with
      intramedullary nailing. Conventionally humerus intramedullary nailing is done
      either using humerus interlocking nails or Enders nails. In this study we analyse
      the outcome of humerus shaft fractures (upper and middle third) managed with
      closed ante-grade intramedullary titanium elastic nailing in terms of union
      rates, union time, functional results and complications. Materials and Methods: A
      retrospective analysis of 25 patients treated with ante-grade intramedullary
      titanium elastic nailing was done during the period of August 2014 to June 2016
      at our tertiary care centre. Skeletally mature patients with closed and acute
      fractures of the upper and middle shaft humerus of both sexes were included in
      the study. Results: Twenty-five (100%) fractures united with an average
      consolidation time of 14.98 weeks (10-32 weeks), and no fractures ended in non
      union. Nail impingement was seen in two (8%), shoulder stiffness in one (4%).
      Functional results were excellent in 22 (88%), moderate in two (8%) and poor in
      one (4%). There were 17 males and eight females with an average age of 39.08
      years (range: 18-65 years). The average duration of hospital stay was 3.84+/-2.30
      days. Conclusion: Closed ante-grade intramedullary titanium elastic nailing
      offers a safe and reliable method of fixing fractures of upper humeral shaft in
      adults. This method provides early fracture union, high union rates and less
      complications, in addition to early rehabilitation and reduces the hospital stay.

PMID- 29021883
TI  - Brodie's Abscess of Posterior Ilium with Gluteal Syndrome, an Unusual Cause of
      Paediatric Low Back Pain: A Case Report.
AB  - Brodie's abscess is a variety of subacute osteomyelitis with a long duration of
      presentation and intermittent pain. It usually involves the metaphyseal region of
      long bones of the lower limbs. Brodie's abscess of pelvic bone is very rare.
      Involvement of posterior ilium with gluteal syndrome is extremely unusual and can
      be easily missed or misdiagnosed. We present a 9-year old boy who reported to us
      with intermittent low back pain of three months duration without any other
      constitutional symptoms. Clinically, there was mild tenderness over the posterior
      ilium. Computed tomography showed a lytic lesion in the posterior ilium with a
      breach in the outer cortex. MRI and bone scan were suggestive of inflammatory
      pathology. Keeping infective, tubercular and benign bone tumors as differential
      diagnoses, open biopsy and curettage were done. Staphylococcus aureus was
      cultured and histopathology was suggestive of osteomyelitis. The patient received
      appropriate antibiotics for six weeks. He was asymptomatic till 18 months of
      follow up without any recurrence. We present this case because of its rarity and
      unusual presentation as gluteal syndrome and low back pain, and its resemblance
      to other pelvic and sacroiliac joint pathologies which are often missed or
      misdiagnosed in paediatric patients.

PMID- 29021884
TI  - Life-threatening Chlorhexidine Anaphylaxis: A Case Report.
AB  - Chlorhexidine is a common antiseptic and disinfectant used in the medical field.
      Allergy to chlorhexidine has been reported in the literature but life-threatening
      anaphylactic shock is rare. We present a case of severe anaphylactic shock due to
      chlorhexidine occurring during surgery. Literatures suggest that profound
      anaphylactic shock to chlorhexidine is commonly preceded by milder, non-specific
      reactions. These mild symptoms are often dismissed by both the patient and
      physicians alike. Direct questioning of these symptoms is necessary as a part of
      the pre-operative assessment and the patient should be referred for further
      immunology testing if indicated.

PMID- 29021885
TI  - Fracture-dislocation at C6-C7 level with Quadriplegia after Traditional Massage
      in a Patient with Ankylosing Spondylitis: A Case Report.
AB  - Ankylosing spinal disorders (ASD) tend to result in fractures and/or dislocations
      after minor trauma because of the altered biomechanical properties. The relative
      risk of traumatic vertebral fractures in patients with ankylosing spondylitis has
      been estimated as three times higher than in the general population. These spine
      traumas, which are located at cervical level in 81% of patients with ankylosing
      spondylitis, are complicated by neurological lesions in 65% of patients, due to
      the high inherent instability of these fractures. Traditional massage is an
      ancient practice in many parts of Asia. It has many benefits that are currently
      recognized world-wide. However, it can be dangerous and even lethal if practised
      without adequate knowledge and skill. We report a case of C6-C7 fracture
      dislocation with complete neurology and neurogenic shock in a middle aged man
      with undiagnosed ankylosing spondylitis.

PMID- 29021886
TI  - Antibiotic-laden Arthroplasty with a Novel Design of Cement Mould and Metallic
      Endoskeleton for Treatment of Hip Infection, an Inexpensive Alternative: A
      Preliminary Report of Two Cases.
AB  - Infection of the hip after implant fixation is an uncommon yet devastating
      complication that results in poor long-term outcome. The gold standard treatment
      for chronic infection after hip arthroplasty is a two-stage protocol: eradication
      of infection, follow by re-implantation arthroplasty. The use of interim
      antibiotic-laden cement spacer has become a popular procedure to maintain hip
      joint function and provide antibiotic elution simultaneously before re
      implantation. However, antibiotic cement spacer is mechanically weak and breaks
      if overloaded. Therefore, we designed a cement mould with metallic endoskeleton
      with the aim of creating a stronger, inexpensive, antibiotic-impregnated spacer
      resembling a unipolar arthroplasty. We report two cases of severe hip joint
      infection after implant fixation (bipolar hemiarthroplasty, screw fixation neck
      of femur). Both patients had undergone first stage surgery of debridement and
      articulating antibiotic cement insertion using our design. Although the second
      stage surgery was planned for these patients, both patients delayed the operation
      in view of good functional status after a year walking with the antibiotic cement
      spacer. These cases showed that the mechanical property of the new antibiotic
      cement spacer was promising but further mechanical studies upon this new
      endoskeleton design are required.

PMID- 29021887
TI  - A Modified Technique of Fixation for Proximal Femoral Valgus Osteotomy in
      Abnormal Bone: A Report of Two Cases.
AB  - The ideal size of intramedullary device to fix corrective osteotomy of proximal
      femur in abnormal bone in children and small patients may not be easily
      available. We report the successful use of Rush rod in combination with multiple
      Kirschner wires to fix the corrective osteotomy of coxa vara and shepherd crook
      deformity in two patients with osteogenesis imperfecta and fibrous dysplasia. The
      union was achieved on time, neck shaft angle and rotation were maintained.

PMID- 29021888
TI  - A Good Short-term Outcome in Delayed Decompression of Cauda Equina Syndrome in
      Klebsiella pneumoniae Spinal Epidural Abscess: A Case Report.
AB  - Spinal epidural abscess is a severe, generally pyogenic, infection of the
      epidural space of spinal cord or cauda equina. The swelling caused by the abscess
      leads to compression or vascular disruption of neurological structures that
      requires urgent surgical decompression to avoid significant permanent disability.
      We share a rare case of Klebsiella pneumoniae spinal epidural abscess secondary
      to haematogenous spread of previous lung infection that presented late at our
      centre with cauda equina syndrome that showed good short-term outcome in delayed
      decompression. A 50-year old female presented with one-week history of persistent
      low back pain with progressively worsening bilateral lower limb weakness for
      seven days and urinary retention associated with saddle anesthesia of 2-day
      duration. Magnetic resonance imaging with contrast of the lumbo-sacral region
      showed an intramuscular collection of abscess at left gluteus maximus and left
      multifidus muscle with a L3-L5 posteriorly placed extradural lesion enhancing
      peripherally on contrast, suggestive of epidural abscess that compressed the
      cauda equina. The pus was drained using the posterior lumbar approach. Tissue and
      pus culture revealed Klebsiella pneumoniae, suggestive of bacterial infection.
      The patient made immediate improvement of muscle power over bilateral lower limbs
      postoperative followed by ability to control micturition and defecation the 4th
      post-operative day. A good short-term outcome in delayed decompression of cauda
      equine syndrome is extremely rare. Aggressive surgical decompression combined
      with antibiotic therapy led to good short-term outcome in this patient despite
      delayed decompression of more than 48 hours.

PMID- 29021891
TI  - A good sugar, d-mannose, suppresses autoimmune diabetes.
AB  - It is well known that too much sugar uptake causes many health problems,
      including diabetes and obesity (Lustig et al. in Nature 482:27-29, 2012).
      However, a team of researchers led by Dr. Wanjun Chen of the National Institute
      of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH),
      USA, have recently shown that d-mannose, a naturally occurring C-2 epimer of
      glucose is likely beneficial to human health. Their studies have revealed that
      supraphysiological levels of d-mannose that are safely achievable via drinking
      water supplementation can be preventive and therapeutic to experimental
      autoimmune diabetes and asthmatic lung inflammation (Zhang et al. in Nat Med
      23:1036-1045, 2017).

PMID- 29021889
TI  - Linguistic camouflage in girls with autism spectrum disorder.
AB  - BACKGROUND: Autism spectrum disorder (ASD) is diagnosed more frequently in boys
      than girls, even when girls are equally symptomatic. Cutting-edge behavioral
      imaging has detected "camouflaging" in girls with ASD, wherein social behaviors
      appear superficially typical, complicating diagnosis. The present study explores
      a new kind of camouflage based on language differences. Pauses during
      conversation can be filled with words like UM or UH, but research suggests that
      these two words are pragmatically distinct (e.g., UM is used to signal longer
      pauses, and may correlate with greater social communicative sophistication than
      UH). Large-scale research suggests that women and younger people produce higher
      rates of UM during conversational pauses than do men and older people, who
      produce relatively more UH. Although it has been argued that children and
      adolescents with ASD use UM less often than typical peers, prior research has not
      included sufficient numbers of girls to examine whether sex explains this effect.
      Here, we explore UM vs. UH in school-aged boys and girls with ASD, and ask
      whether filled pauses relate to dimensional measures of autism symptom severity.
      METHODS: Sixty-five verbal school-aged participants with ASD (49 boys, 16 girls,
      IQ estimates in the average range) participated, along with a small comparison
      group of typically developing children (8 boys, 9 girls). Speech samples from the
      Autism Diagnostic Observation Schedule were orthographically transcribed and time
      aligned, with filled pauses marked. Parents completed the Social Communication
      Questionnaire and the Vineland Adaptive Behavior Scales. RESULTS: Girls used UH
      less often than boys across both diagnostic groups. UH suppression resulted in
      higher UM ratios for girls than boys, and overall filled pause rates were higher
      for typical children than for children with ASD. Higher UM ratios correlated with
      better socialization in boys with ASD, but this effect was driven by increased
      use of UH by boys with greater symptoms. CONCLUSIONS: Pragmatic language markers
      distinguish girls and boys with ASD, mirroring sex differences in the general
      population. One implication of this finding is that typical-sounding disfluency
      patterns (i.e., reduced relative UH production leading to higher UM ratios) may
      normalize the way girls with ASD sound relative to other children, serving as
      "linguistic camouflage" for a naive listener and distinguishing them from boys
      with ASD. This first-of-its-kind study highlights the importance of continued
      commitment to understanding how sex and gender change the way that ASD manifests,
      and illustrates the potential of natural language to contribute to objective
      "behavioral imaging" diagnostics for ASD.

PMID- 29021892
TI  - Catching global interactions in vivo.
AB  - Histone proteins and transcription factors (TFs) play critical roles in gene
      transcription and development of multicellular organisms. Although antibody
      mediated protein isolation couple with mass spectrometry approach has been a
      standard method to identify TF interacting partners and characterize their
      functional molecular complexes, it becomes urge to develop a robust method to
      functional characterize how these transcription factors act during biological
      process in the post-human genome project era. Here, Dr. Zhao and his colleagues
      in the National Heart, Lung, and Blood Institute of NIH develop a sensitive and
      robust strategy to globally identify and characterize in vivo protein-protein
      interactions termed bait protein-protein interaction-sequencing (bPPI-seq) (Zhang
      et al. in Cell Res doi:10.1038/cr.2017.112, 2017). As a proof-of-principle, they
      demonstrated that genome-wide interacting partners of histone variant H2A.Z are
      mainly involved in transcriptional regulation which is distinct from the
      interacting proteins of canonical histone H2A. Thus, their results suggest that
      bPPI-seq can be widely used to globally characterize protein complexes especially
      transcription factor interacting partners and molecular networks formed.

PMID- 29021890
TI  - Zebrafish knockout of Down syndrome gene, DYRK1A, shows social impairments
      relevant to autism.
AB  - BACKGROUND: DYRK1A maps to the Down syndrome critical region at 21q22. Mutations
      in this kinase-encoding gene have been reported to cause microcephaly associated
      with either intellectual disability or autism in humans. Intellectual disability
      accompanied by microcephaly was recapitulated in a murine model by overexpressing
      Dyrk1a which mimicked Down syndrome phenotypes. However, given embryonic
      lethality in homozygous knockout (KO) mice, no murine model studies could present
      sufficient evidence to link Dyrk1a dysfunction with autism. To understand the
      molecular mechanisms underlying microcephaly and autism spectrum disorders (ASD),
      we established an in vivo dyrk1aa KO model using zebrafish. METHODS: We
      identified a patient with a mutation in the DYRK1A gene using microarray
      analysis. Circumventing the barrier of murine model studies, we generated a
      dyrk1aa KO zebrafish using transcription activator-like effector nuclease (TALEN)
      mediated genome editing. For social behavioral tests, we have established a
      social interaction test, shoaling assay, and group behavior assay. For molecular
      analysis, we examined the neuronal activity in specific brain regions of dyrk1aa
      KO zebrafish through in situ hybridization with various probes including c-fos
      and crh which are the molecular markers for stress response. RESULTS: Microarray
      detected an intragenic microdeletion of DYRK1A in an individual with microcephaly
      and autism. From behavioral tests of social interaction and group behavior,
      dyrk1aa KO zebrafish exhibited social impairments that reproduce human phenotypes
      of autism in a vertebrate animal model. Social impairment in dyrk1aa KO zebrafish
      was further confirmed by molecular analysis of c-fos and crh expression.
      Transcriptional expression of c-fos and crh was lower than that of wild type fish
      in specific hypothalamic regions, suggesting that KO fish brains are less
      activated by social context. CONCLUSIONS: In this study, we established a
      zebrafish model to validate a candidate gene for autism in a vertebrate animal.
      These results illustrate the functional deficiency of DYRK1A as an underlying
      disease mechanism for autism. We also propose simple social behavioral assays as
      a tool for the broader study of autism candidate genes.

PMID- 29021893
TI  - The efficacy of oral and subcutaneous antigen-specific immunotherapy in murine
      cow's milk- and peanut allergy models.
AB  - BACKGROUND: Antigen-specific immunotherapy (AIT) is a promising therapeutic
      approach for both cow's milk allergy (CMA) and peanut allergy (PNA), but needs
      optimization in terms of efficacy and safety. AIM: Compare oral immunotherapy
      (OIT) and subcutaneous immunotherapy (SCIT) in murine models for CMA and PNA and
      determine the dose of allergen needed to effectively modify parameters of
      allergy. METHODS: Female C3H/HeOuJ mice were sensitized intragastrically (i.g.)
      to whey or peanut extract with cholera toxin. Mice were treated orally (5
      times/week) or subcutaneously (3 times/week) for three consecutive weeks.
      Hereafter, the acute allergic skin response, anaphylactic shock symptoms and body
      temperature were measured upon intradermal (i.d.) and intraperitoneal (i.p.)
      challenge, and mast cell degranulation was measured upon i.g. challenge. Allergen
      specific IgE, IgG1 and IgG2a were measured in serum at different time points.
      Single cell suspensions derived from lymph organs were stimulated with allergen
      to induce cytokine production and T cell phenotypes were assessed using flow
      cytometry. RESULTS: Both OIT and SCIT decreased clinically related signs upon
      challenge in the CMA and PNA model. Interestingly, a rise in allergen-specific
      IgE was observed during immunotherapy, hereafter, treated mice were protected
      against the increase in IgE caused by allergen challenge. Allergen-specific IgG1
      and IgG2a increased due to both types of AIT. In the CMA model, SCIT and OIT
      reduced the percentage of activated Th2 cells and increased the percentage of
      activated Th1 cells in the spleen. OIT increased the percentage of regulatory T
      cells (Tregs) and activated Th2 cells in the MLN. Th2 cytokines IL-5, IL-13 and
      IL-10 were reduced after OIT, but not after SCIT. In the PNA model, no
      differences were observed in percentages of T cell subsets. SCIT induced Th2
      cytokines IL-5 and IL-10, whereas OIT had no effect. CONCLUSION: We have shown
      clinical protection against allergic manifestations after OIT and SCIT in a CMA
      and PNA model. Although similar allergen-specific antibody patterns were
      observed, differences in T cell and cytokine responses were shown. Whether these
      findings are related to a different mechanism of AIT in CMA and PNA needs to be
      elucidated.

PMID- 29021894
TI  - Occupational stress and the importance of self-care and resilience: focus on
      veterinary nursing.
AB  - BACKGROUND: Burnout and compassion fatigue are frequently mentioned in relation
      to veterinary work. Veterinary nursing is a caring profession and those who seek
      a career within this field do so because of a natural empathetic desire to care
      for animals. However it is the individuals who are the most caring and empathetic
      towards others that will be most at risk of experiencing occupational stress when
      they are confronted with psychologically demanding workplace roles and working
      environments. MAIN BODY: Burnout is considered an 'unintentional end point' for
      certain individuals who are exposed to chronic stress within their working
      environment. When suffering burnout, a person may experience emotional
      exhaustion, may become more cynical or they may have a reduced sense of personal
      accomplishment in regards to their own work. Signs of burnout can include
      increased levels of absenteeism at work, or the working standards of that staff
      member may decline below that of what would normally be expected of them. This
      could directly impact on patient care in the veterinary practice. Working in a
      role that places emotional demands on staff, such as a need to show compassion
      and empathy towards clients who are emotionally distressed, puts staff at risk
      from experiencing compassion fatigue. Workplace supports may include appropriate
      debriefing sessions among willing participants, particularly after an emotionally
      stressful encounter with a client. Taking personal responsibility for care of
      one's own mental and physical health is just as important as taking care of the
      patient's health. Personal strategies may include lifestyle changes, adopting a
      healthier lifestyle, reduction of working hours, and ensuring adequate sleep.
      Adopting healthy self-care strategies can promote characteristics of "resilience"
      - personal qualities or traits such as optimism, self-confidence, level
      headedness, hardiness, and having the ability to be resourceful during times of
      adversity. CONCLUSION: All veterinary staff may be better prepared to deal with
      occupational stress related conditions if they gain better insight and ability to
      recognise the condition in self and others, and if provided with the toolkits to
      develop coping strategies and resilience.

PMID- 29021895
TI  - Readiness for antimicrobial resistance (AMR) surveillance in Pakistan; a model
      for laboratory strengthening.
AB  - BACKGROUND: Limited capacity of laboratories for antimicrobial susceptibility
      testing (AST) presents a critical diagnostic bottleneck in resource limited
      countries. This paper aims to identify such gaps and to explore whether
      laboratory networks could contribute towards improving AST in low resource
      settings. METHODS: A self-assessment tool to assess antimicrobial susceptibility
      testing capacity was administered as a pre-workshop activity to participants from
      30 microbiology laboratories in 3 cities in Pakistan. Data from public and
      private laboratories was analyzed and capacity of each scored in percentage
      terms. Laboratories from Karachi were invited to join a support network. A cohort
      of five laboratories that consented were provided additional training and updates
      sessions over a period of 15 months. Impact of training activities in these
      laboratories was evaluated using a point scoring (0-11) tool. RESULTS: Results of
      self-assessment component identified a number of areas that required
      strengthening (scores of <=60%). These included; readiness for AMR surveillance;
      38 and 46%, quality assurance; 49 and 55%, and detection of specific organisms;
      56 and 60% for public and private laboratories respectively. No significant
      difference was detected in AST capacity between public and private laboratories
      [ANOVA; p > 0.05]. Scoring tool used to assess impact of training within the
      longitudinal cohort showed an increase from a baseline of 1-5.5 (August 2015) to
      improved post training scores of 7-11 (October 2016) for the 5 laboratories
      included. Moreover, statistical analysis using paired t-Test Analysis, assuming
      unequal variance, indicated that the increase in scored noted represents a
      statistically significant improvement in the components evaluated [p < 0.05].
      CONCLUSION: Strengthening of laboratory capacity for AMR surveillance is
      important. Our data shows that close mentoring and support can help enhance
      capacity for antimicrobial sensitivity testing in resource limited settings. Our
      study further presents a model wherein laboratory networks can be successfully
      established and used towards improving diagnostic capacity in such settings.

PMID- 29021897
TI  - Patient outcome of emergency laparotomy improved with increasing "number of
      surgeons on-call" in a university hospital: Audit loop.
AB  - AIM: Emergency laparotomy is a commonly performed high-mortality surgical
      procedure. The National Emergency Laparotomy Network (NELA) published an average
      mortality rate of 11.1% and a median length of stay equivalent to 16.3 days in
      patients undergoing emergency laparotomy. This study presents a completed audit
      loop after implementing the change of increasing the number of on-call surgeons
      in the general surgery rota of a university hospital. The aim of this study was
      to evaluate the outcomes of emergency laparotomy in a single UK tertiary centre
      after addition of one more consultant in the daily on-call rota. METHODS: This is
      a retrospective study involving patients who underwent emergency laparotomy
      between March to May 2013 (first audit) and June to August 2015 (second audit).
      The study parameters stayed the same. The adult patients undergoing emergency
      laparotomy under the general surgical take were included. Appendicectomy,
      cholecystectomy and simple inguinal hernia repair patients were excluded. Data
      was collected on patient demographics, ASA, morbidity, 30-day mortality and
      length of hospital stay. Statistical analysis including logistic regression was
      performed using SPSS. RESULTS: During the second 3-month period, 123 patients
      underwent laparotomy compared to 84 in the first audit. Median age was 65(23-93)
      years. 56.01% cases were ASA III or above in the re-audit compared to 41.9% in
      the initial audit. 38% patients had bowel anastomosis compared to 35.7% in the re
      audit with 4.2% leak rate in the re-audit compared to 16.6% in the first audit.
      30-day mortality was 10.50% in the re-audit compared to 21% and median length of
      hospital stay 11 days in the re-audit compared to 16 days. The lower ASA grade
      was significantly associated with increased likelihood of being alive, as was
      being female, younger age and not requiring ITU admission post-operatively.
      However, having a second on-call consultant was 2.231 times more likely to
      increase the chances of patients not dying (p = 0.031). CONCLUSION: Our audit
      loop suggests that adding a second consultant to the daily on-call rota
      significantly reduces postoperative mortality and morbidity. Age, ASA and ITU
      admission are other independent factors affecting patient outcomes. We suggest
      this change be applied to other high volume centres across the country to improve
      the outcomes after emergency laparotomy.

PMID- 29021896
TI  - Disease modification and Neuroprotection in neurodegenerative disorders.
AB  - BACKGROUND: Disease modifying therapies (DMTs) are urgently needed for
      neurodegenerative diseases (NDD) such as Alzheimer's disease (AD) and many other
      disorders characterized by protein aggregation and neurodegeneration. Despite
      advances in understanding the neurobiology of NDD, there are no approved DMTs.
      DISCUSSION: Defining disease-modification is critical to drug-development
      programs. A DMT is an intervention that produces an enduring change in the
      trajectory of clinical decline of an NDD by impacting the disease processes
      leading to nerve cell death. A DMT is neuroprotective, and neuroprotection will
      result in disease modification. Disease modification can be demonstrated in
      clinical trials by a drug-placebo difference in clinical outcomes supported by a
      drug-placebo difference on biomarkers reflective of the fundamental
      pathophysiology of the NDD. Alternatively, disease modification can be supported
      by findings on a staggered start or delayed withdrawal clinical trial design.
      Collecting multiple biomarkers is necessary to support a comprehensive view of
      disease modification. CONCLUSION: Disease modification is established by
      demonstrating an enduring change in the clinical trajectory of an NDD based on
      intervention in the fundamental pathophysiology of the disease leading to nerve
      cell death. Supporting data are collected in clinical trials. Effectively
      defining a DMT will assist in NDD drug development programs.

PMID- 29021898
TI  - A case report and approach to management in pneumatosis intestinalis.
AB  - Pneumatosis Intestinalis (PI) is an uncommon condition in which there is gas
      present within the wall of the gastrointestinal tract. PI is usually found in the
      large bowel, but can less commonly occur in the small bowel, and gas may be
      present in either the subserosal or submucosal layer of the intestine. Its
      unfamiliarity often means it is under-recognised and not considered as a
      differential diagnosis when assessing a patient with abdominal symptoms. The
      spectrum of conditions that produce PI is varied and ranges from the non-urgent
      to life-threatening. Early appreciation of the overall clinical picture is
      therefore paramount to enable the practitioner to distinguish between the benign
      to the fatal cases of PI and enable precise decision-making regarding its
      management. The challenge facing the clinician is twofold; firstly the accurate
      identification of the diagnosis of PI, as opposed to other causes of peritoneal
      gas and secondly judging whether operative or non-operative management should
      ensue. We present a case of a patient presenting on two separate occasions with
      PI, abdominal symptoms and radiological signs of acute abdominal pathology which
      demonstrates the wide spectrum of difficulties faced with this uncommon
      condition.

PMID- 29021900
TI  - A content analysis of thinspiration, fitspiration, and bonespiration imagery on
      social media.
AB  - BACKGROUND: On social media, images such as thinspiration, fitspiration, and
      bonespiration, are shared to inspire certain body ideals. Previous research has
      demonstrated that exposure to these groups of content is associated with
      increased body dissatisfaction and decreased self-esteem. It is therefore
      important that the bodies featured within these groups of content are more fully
      understood so that effective interventions and preventative measures can be
      informed, developed, and implemented. METHOD: A content analysis was conducted on
      a sample of body-focussed images with the hashtags thinspiration, fitspiration,
      and bonespiration from three social media platforms. RESULTS: The analyses showed
      that thinspiration and bonespiration content contained more thin and objectified
      bodies, compared to fitspiration which featured a greater prevalence of muscles
      and muscular bodies. In addition, bonespiration content contained more bone
      protrusions and fewer muscles than thinspiration content. CONCLUSIONS: The
      findings suggest fitspiration may be a less unhealthy type of content; however, a
      subgroup of imagery was identified which idealised the extremely thin body type
      and as such this content should also be approached with caution. Future research
      should utilise qualitative methods to further develop understandings of the body
      ideals that are constructed within these groups of content and the motivations
      behind posting this content.

PMID- 29021899
TI  - Reliability of self-report measures of correlates of obesity-related behaviours
      in Hong Kong adolescents for the iHealt(H) and IPEN adolescent studies.
AB  - BACKGROUND: This study examined the reliability of measures of correlates of
      dietary behaviours (DBs), physical activity (PA) and sedentary behaviour (SB) for
      Hong Kong adolescents. METHOD: Individual, social and environmental correlates of
      obesity-related behaviours were assessed twice, 15-27 days apart (average 20
      days), via self-administered questionnaires. These questionnaire included
      measures of decisional balance, self-efficacy, enjoyment and social support
      related to intake of fruits, vegetables, high-fat foods and sugar-sweetened
      beverages, PA behaviour and SB. They also included measures of perceived barriers
      to PA, parental rules related to PA and SB, and environmental correlates of DB,
      PA and SB. The questionnaires were self-completed outside school hours. A sample
      of 119 12-17 year old Chinese-speaking secondary school students (60 girls; 59
      boys) were recruited from four Hong Kong schools located in areas stratified by
      walkability and socio-economic status. RESULTS: The test-retest reliability of
      the examined measures ranged from poor to excellent (ICC: 0.30-0.99). All
      measures of correlates of PA and SB had excellent or substantial test-retest
      reliability, with the exception of self-efficacy for reducing SB (ICC: 0.59).
      Four of 18 measures of DBs showed moderate, and two poor (ICC < 0.41), test
      retest reliability. Evidence of unidimensionality (Cronbach's alpha >= 0.70) was
      found for 10 of 28 multi-item scales. The evidence for the remaining 18 was
      either questionable or poor. CONCLUSIONS: Most of the self-report measures of
      correlates of obesity-related behaviours used in the iHealt(H) study have
      acceptable test-retest reliability in Hong Kong adolescents. The factorial
      structure of several scales needs to be investigated in a larger sample.

PMID- 29021901
TI  - ICSI diagnostic: a way to prevent total fertilization failure after 4
      unsuccessful IUI.
AB  - BACKGROUND: The aim of this retrospective study is to investigate the relevance
      of dividing oocytes and using some for traditional in vitro fertilization (IVF)
      and others for intracytoplasmic sperm injection (ICSI) as of the first IVF cycle
      in patients with unexplained infertility who have undergone 4 intrauterine
      insemination (IUI) cycles which produced no pregnancies. METHODS: This
      retrospective study includes patients with unexplained infertility who have
      failed to become pregnant, after 4 IUI, despite normal semen parameters after
      sperm capacitation. These women were treated in our assisted fertilization
      program from 2008 until 2015. We analysed the first cycles of women in whom more
      than 4 oocyte cumulus complexes (OCC) were retrieved and single embryo transfer
      was performed. RESULTS: Dividing oocytes between two fertilization techniques
      reduce the rate of total fertilization failure during the first IVF cycle. No
      statistical difference were observed for 2 pronuclei (PN) rate between the two
      techniques. On the other hand, we observed a significantly lower rate of 3 PN, 1
      PN, 0 PN with ICSI in comparison with conventional fertilization. CONCLUSIONS:
      Splitting the oocytes between classical IVF and ICSI increases the chance of
      embryo transfer on a first IVF cycle after 4 unsuccessful IUI cycles. This half
      and-half policy reduces the risk, for the infertile couple, of facing total
      failure of fertilization and also can provide useful information for the next
      attempts.

PMID- 29021903
TI  - 'Clostridium mediterraneense,' a new bacterial species isolated from the human
      gut.
AB  - We report the main characteristics of 'Clostridium mediterraneense' sp. nov.,
      strain Marseille-P2434T (CSUR P2434), a new species within the genus Clostridium.
      This strain was isolated from the gut microbiota of a 66-year-old diabetic
      patient in Marseille, France.

PMID- 29021902
TI  - Significantly elevated foetal haemoglobin levels in individuals with glucose 6
      phosphate dehydrogenase disease and/or sickle cell trait: a cross-sectional study
      in Cape Coast, Ghana.
AB  - BACKGROUND: Previously published data have demonstrated that sickle red blood
      cells produce twice as much reactive oxygen species (ROS) suggesting that co
      inheritance of sickle cell disease (SCD) and glucose 6-phosphate dehydrogenase
      (G6PD) enzymopathy could lead to more severe anaemia during sickling crises.
      Elevated foetal haemoglobin (Hb F) levels have been shown to have positive
      modulatory effects on sickling crises and disease outcomes. This study sought to
      assess how inheritance of G6PD enzymopathy affects the level of Hb F and
      haemoglobin concentration in adults in steady state. METHODS: This cross
      sectional study selected 100 out-patients (41 males and 59 females) visiting the
      University of Cape Coast hospital, between January, 2016 and May, 2016. Cellulose
      acetate electrophoresis (pH 8.2-8.6), methaemoglobin reductase test, modified
      Betke alkaline denaturation methods were used to investigate haemoglobin
      variants, qualitative G6PD status, and %Hb F levels in venous blood samples drawn
      from these participants. Data was analysed with GraphPad Prism 6 and SPSS and
      significance set at p < 0.05. RESULTS: Forty one percent of the participants
      demonstrated qualitative G6PD enzymopathy whereas only 10% demonstrated Hb AS
      type (Sickle cell trait, SCT). 5% of the participants co-inherited SCT and G6PD
      enzymopathy. %Hb F levels in G6PD deficient males was significantly higher than
      in G6PD deficient females [(p = 0.0003, 2.696% (males) vs 1.975% (females)],
      although the %Hb F levels was comparable in non-G6PD deficient individuals. %Hb F
      levels were significantly elevated in males with SCT only (p < 0.05), or G6PD
      enzymopathy only (p < 0.0001), or SCT + G6PD enzymopathy (p < 0.0001) compared to
      males with none of these pathologies even though their respective haemoglobin
      levels were comparable. Male participants with G6PD enzymopathy + SCT co
      inheritance had significantly elevated %Hb F when compared to their counterparts
      with only G6PD enzymopathy (p < 0.001). Male gender [(p = 0.001, OR: 6.912 (2.277
      20.984)] partial defective G6PD enzyme [(p = 0.00, OR: 7.567E8 (8.443E7-6.782E9)]
      SCT [(p = 0.026, OR: 4.625 (1.196-17.881)] were factors associated with raised
      %Hb F levels >=2.5. CONCLUSION: The inheritance of G6PD defect and/or SCT
      significantly elevate %Hb F levels in the steady state even though haemoglobin
      levels are not affected.

PMID- 29021904
TI  - A study of ribonuclease activity in venom of vietnam cobra.
AB  - BACKGROUND: Ribonuclease (RNase) is one of the few toxic proteins that are
      present constantly in snake venoms of all types. However, to date this RNase is
      still poorly studied in comparison not only with other toxic proteins of snake
      venom, but also with the enzymes of RNase group. The objective of this paper was
      to investigate some properties of RNase from venom of Vietnam cobra Naja atra.
      METHODS: Kinetic methods and gel filtration chromatography were used to
      investigate RNase from venom of Vietnam cobra. RESULTS: RNase from venom of
      Vietnam cobra Naja atra has some characteristic properties. This RNase is a
      thermostable enzyme and has high conformational stability. This is the only
      acidic enzyme of the RNase A superfamily exhibiting a high catalytic activity in
      the pH range of 1-4, with pHopt = 2.58 +/- 0.35. Its activity is considerably
      reduced with increasing ionic strength of reaction mixture. Venom proteins are
      separated by gel filtration into four peaks with ribonucleolytic activity, which
      is abnormally distributed among the isoforms: only a small part of the RNase
      activity is present in fractions of proteins with molecular weights of 12-15 kDa
      and more than 30 kDa, but most of the enzyme activity is detected in fractions of
      polypeptides, having molecular weights of less than 9 kDa, that is unexpected.
      CONCLUSIONS: RNase from the venom of Vietnam cobra is a unique member of RNase A
      superfamily according to its acidic optimum pH (pHopt = 2.58 +/- 0.35) and
      extremely low molecular weights of its major isoforms (approximately 8.95 kDa for
      RNase III and 5.93 kDa for RNase IV).

PMID- 29021905
TI  - The waterpolo shoulder paradigm: results of ultrasound surveillance at poolside.
AB  - BACKGROUND: Waterpolo consists of a combination of swimming and throwing with
      close contact between players. The shoulder is the most frequently injured joint,
      with a combination of rotator cuff tear and tendinopathy, long head biceps
      tendinopathy, superior labral lesions and shoulder impingement. This unique
      combination is a challenge for the clinician who must determine which of these
      shoulder pathologies is responsible for the onset of pain and the best strategy
      to rehabilitate the joint and prevent recurrence. AIM: The aim of this study was
      to estimate with ultrasound the frequency and characteristics of shoulder
      injuries in waterpolo players competing in different leagues. METHODS: Forty-two
      players from two clubs in the premier and second Italian league were enrolled in
      the study. Standard and dynamic shoulder ultrasound scans were performed on all
      athletes. RESULTS: Ultrasound investigation showed that almost all players had
      injuries of the shoulders; only four players did not show any shoulder
      modification. Thirteen athletes who had shoulder pain during the ultrasound
      examination showed subacromion deltoid bursitis and/or long head biceps
      tendinitis. No statistically significant differences in the frequency and
      characteristics of shoulder modifications or injuries were detected between
      players of the premier or second league. CONCLUSION: Shoulder injuries are very
      common in waterpolo players and comprise a peculiar and complex combination of
      rotator cuff tendinopathy and tears, long head biceps tendinopathy, impingement,
      subacromion deltoid bursitis and superior labral lesions. The use of ultrasound
      has been shown to be of considerable help in highlighting the modifications of
      the shoulder structures at an early asymptomatic stage. The ability to perform
      real-time scanning at the poolside makes ultrasound a useful tool in the rapid
      management and regular follow-up of shoulder modifications in everyday practice
      in sport medicine.

PMID- 29021906
TI  - A pilot biomechanical assessment of curling deliveries: is toe sliding more
      likely to cause knee injury than flatfoot sliding?
AB  - BACKGROUND: The aim of this study was to determine whether toe sliding is more
      likely to cause knee injuries than flatfoot sliding in curling. METHODS: Twelve
      curlers participated in the study, each delivering 12 stones. Six stones per
      volunteer were delivered using a flatfoot slide and six were delivered using a
      toe slide. The Pedar-X in-shoe pressure system recorded the plantar pressure
      during each of the slides, while a sagittal plane digital video recorded the body
      position of the curler. Measurements were taken from the video recordings using a
      software overlay program (MB Ruler), and this, combined with the Pedar-X data,
      gave the overall joint force in the tuck knee. RESULTS: The knee joint force for
      toe sliding was more than double that of flatfoot sliding (p<0.05). There was a
      strong correlation between the increase in knee joint force and the increase in
      the moment arm of the ground reaction force. Images produced using the three
      dimensional Vicon system confirm that toe sliding produces a larger moment arm
      than flatfoot sliding. CONCLUSION: Injuries are more likely to occur in toe
      sliding, compared with flatfoot sliding, due to the increase in force and moment,
      pushing the weight of the curler forward over the knee, which could make the
      adopted position less stable. Curlers might consider avoiding toe sliding to
      reduce the risk of knee injuries if the two types of delivery could be performed
      equally well.

PMID- 29021907
TI  - Lessons from Popper for science, paradigm shifts, scientific revolutions and
      exercise physiology.
AB  - A connection has been made to the possible role of the central governor model
      (CGM) to be a paradigm shift within the exercise sciences. Unfortunately, very
      little evidence was presented to support this notion, and a narrow view of
      scientific philosophy was used to reflect on the role of the CGM in understanding
      exercise physiology and the pursuit of a more ideal scientific method. When
      contrasting the scientific philosophies of Kuhn to Popper, and applying the
      tenant of falsification to the research and commentary on the CGM, it is probable
      that the scholarship pertaining to the CGM adheres more to pseudoscience than
      science. To improve the scientific contributions of research on the CGM, fellow
      scientists need to adopt a more critical platform where questions are raised and
      research designs are employed in efforts to refute the theory. The inability to
      falsify a theory is the most meaningful way to prove that it is likely to be
      correct. To support this development, the CGM needs to be more carefully worded
      to form a theory that clearly reveals key features that can be researched and
      potentially falsified. In addition, the wording of the CGM needs to allow
      scientists to make predictions that can then be tested in controlled experimental
      research studies. Until this happens for the CGM and all other pertinent
      paradigms within exercise physiology, the discipline will never rise out of the
      abyss of normal science to extraordinary science involving paradigm shifts and
      scientific revolutions.

PMID- 29021909
TI  - Managing diabetes at high altitude: personal experience with support from a
      Multidisciplinary Physical Activity and Diabetes Clinic.
AB  - OBJECTIVE: Physical activity is important for well-being but can be challenging
      for people with diabetes. Data informing support of specialist activities such as
      climbing and high-altitude trekking are limited. A 42-year-old man with type 1
      diabetes (duration 30 years) attended a Multidisciplinary Physical Activity and
      Diabetes Clinic planning to climb Mont Blanc during the summer and trek to
      Everest Base Camp in the autumn. His aims were to complete these adventures
      without his diabetes impacting on their success. METHODS: We report the
      information provided that enabled him to safely facilitate his objectives, in
      particular, the requirement for frequent checking of blood glucose levels, the
      effects of altitude on insulin dose requirements, and recognition that acute
      mountain sickness may mimic the symptoms of hypoglycaemia and vice versa. Real
      time continuous glucose monitoring was made available for his treks. RESULTS: The
      effects of high altitude on blood glucose results and glycaemic variability while
      treated on multiple daily injections of insulin are reported. In addition, we
      present a first-person account of his experience and lessons learnt from managing
      diabetes at high altitude. CONCLUSIONS: A dedicated Multidisciplinary Physical
      Activity and Diabetes Clinic delivering individualised, evidence-based, patient
      focused advice on the effects of altitude on blood glucose levels, and provision
      of real-time continuous glucose monitoring enabled uneventful completion of a
      trek to Everest Base Camp in a person with type 1 diabetes.

PMID- 29021908
TI  - Effectiveness of a standardised exercise programme for recurrent neck and low
      back pain: a multicentre, randomised, two-arm, parallel group trial across 34
      fitness clubs in Finland.
AB  - BACKGROUND: Neck and low back pain (LBP) are common in office workers. Exercise
      trials to reduce neck and LBP conducted in sport sector are lacking. We
      investigated the effectiveness of the standardised Fustra20Neck&Back exercise
      program for reducing pain and increasing fitness in office workers with recurrent
      non-specific neck and/or LBP. METHOD: Volunteers were recruited through newspaper
      and Facebook. The design is a multi-centre randomised, two-arm, parallel group
      trial across 34 fitness clubs in Finland. Eligibility was determined by
      structured telephone interview. Instructors were specially educated
      professionals. Neuromuscular exercise was individually guided twice weekly for 10
      weeks. Webropol survey, and objective measurements of fitness, physical activity,
      and sedentary behavior were conducted at baseline, and at 3 and 12 months. Mean
      differences between study groups (Exercise vs Control) were analysed using a
      general linear mixed model according to the intention-to-treat principle.
      RESULTS: At least moderate intensity pain (>=40 mm) in both the neck and back was
      detected in 44% of participants at baseline. Exercise compliance was excellent:
      92% participated 15-20 times out of 20 possible. Intensity and frequency of neck
      pain, and strain in neck/shoulders decreased significantly in the Exercise group
      compared with the Control group. No differences in LBP and strain were detected.
      Neck/shoulder and trunk flexibility improved, as did quality of life in terms of
      pain and physical functioning. CONCLUSIONS: The Fustra20Neck&Back exercise
      program was effective for reducing neck/shoulder pain and strain, but not LBP.
      Evidence-based exercise programs of sports clubs have potential to prevent
      persistent, disabling musculoskeletal problems.

PMID- 29021911
TI  - Interval exercise increases angiogenic cell function in postmenopausal women.
AB  - INTRODUCTION: Exercise can help to negate the increased cardiovascular disease
      risk observed in women after the menopausal transition. This study sought to
      determine whether interval or continuous exercise has differential effects on
      endothelial function and circulating angiogenic cell (CAC) number and function in
      postmenopausal women. METHODS: Fifteen healthy postmenopausal women completed a
      30 min acute moderate-intensity continuous (CON) and interval exercise (MOD-INT)
      session on a cycle ergometer on separate days. Nine participants completed a
      further single 30 min acute heavy-intensity interval (HEAVY-INT) exercise
      session. Brachial artery flow-mediated dilation (FMD) was assessed pre-exercise
      and 15 min post-exercise session. CAC number and colony-forming capacity in vitro
      were assessed post exercise and compared with resting levels. RESULTS: FMD and
      CAC number did not change post exercise regardless of exercise type (p>0.05).
      However, the number (mean+/-SD) of colony-forming units (CFUs) increased from
      visit 1 (12+/-10 CFUs/well) to post MOD-INT (32+/-30 CFUs/well) and post HEAVY
      INT (38+/-23 CFUs/well) but not post CON (13+/-14 CFUs/well). CONCLUSION: A
      single session of interval exercise is more effective than a continuous exercise
      session for increasing the intercellular communication of CACs, regardless of
      exercise intensity. The enhanced ability of CACs to form colonies may reflect an
      increased number and/or function of angiogenic T-cells. The repeated exertions to
      higher work rates during interval exercise may explain this response. Repeated
      exercise sessions might be required to improve FMD in postmenopausal women.

PMID- 29021910
TI  - The training type influence on male elite athletes' ventilatory function.
AB  - BACKGROUND/AIM: To assess and compare measured ventilatory volumes (forced
      expiratory volume in 1 s (FEV1), peak expirium flow (PEF) and maximal voluntary
      ventilation (MVV)), ventilatory function capacities (forced vital capacity (FVC)
      and vital capacity (VC)) and FEV1/VC ratio in a sample of power and endurance
      elite athletes and their age-matched and sex-matched sedentary control group.
      METHODS: A cross-sectional study was applied on male elite athletes (n=470) who
      were classified according to the type of the predominantly performed exercise in
      the following way: group 1: endurance group (EG=270), group 2: power athletes
      group (SG=200) and group 3: sedentary control group (CG=100). The lung VC, FVC,
      FEV1, FEV1/FVC ratio, PEF and MVV were measured in all of the observed subjects,
      who were also classified with regard to body mass index (BMI) and the percentage
      of the body fat (BF%). RESULTS: The CG had the highest BF% value, while the
      endurance group had the lowest BMI and BF% value, which is significantly
      different from the other two groups (p<0.05). The observed values of VC, FVC and
      FEV1 in the EG were significantly higher than those from the other two groups
      (p<0.05). There were no differences concerning the observed FEV1/FVC ratio.
      CONCLUSIONS: A continued endurance physical activity leads to adaptive changes in
      spirometric parameters (VC, FVC and FEV1), highlighting the fact that there is a
      need for specific consideration of different respiratory 'pattern' development in
      different types of sport, which also has to be further evaluated.

PMID- 29021912
TI  - A study of intensity, fatigue and precision in two specific interval trainings in
      young tennis players: high-intensity interval training versus intermittent
      interval training.
AB  - BACKGROUND: The aim of this study is to find the differences between two specific
      interval exercises. We begin with the hypothesis that the use of microintervals
      of work and rest allow for greater intensity of play and a reduction in fatigue.
      METHODS: Thirteen competition-level male tennis players took part in two interval
      training exercises comprising nine 2 min series, which consisted of hitting the
      ball with cross-court forehand and backhand shots, behind the service box. One
      was a high-intensity interval training (HIIT), made up of periods of continuous
      work lasting 2 min, and the other was intermittent interval training (IIT), this
      time with intermittent 2 min intervals, alternating periods of work with rest
      periods. Average heart rate (HR) and lactate levels were registered in order to
      observe the physiological intensity of the two exercises, along with the Borg
      Scale results for perceived exertion and the number of shots and errors in order
      to determine the intensity achieved and the degree of fatigue throughout the
      exercise. RESULTS: There were no significant differences in the average heart
      rate, lactate or the Borg Scale. Significant differences were registered, on the
      other hand, with a greater number of shots in the first two HIIT series (series 1
      p>0.009; series 2 p>0.056), but not in the third. The number of errors was
      significantly lower in all the IIT series (series 1 p<0.035; series 2 p<0.010;
      series 3 p<0.001). CONCLUSION: Our study suggests that high-intensity
      intermittent training allows for greater intensity of play in relation to the
      real time spent on the exercise, reduced fatigue levels and the maintaining of
      greater precision in specific tennis-related exercises.

PMID- 29021913
TI  - Exergaming can be an innovative way of enjoyable high-intensity interval
      training.
AB  - OBJECTIVES: Exergames can replace sedentary time spent on computer gaming with
      physical activity. Previous research has found exergaming to elicit light-to
      moderate exercise intensity. Our primary aim was to examine the exercise
      intensity of a newly developed biking exergame. METHODS: Eight males (23.9+/-0.6
      years) played the exergame (PLAY) and walked (WALK) on three separate occasions,
      with the condition counterbalanced and in random sequence within each day. They
      were asked to PLAY and WALK for a minimum of 15 min and then continue for as long
      as they wanted. We measured heart rate (HR), activity duration, caloric
      expenditure and subject-rated exertion and enjoyment (based on 0-10 Visual
      Analogue Scale, VAS). We used an average of each outcome variable across the 3
      days in the analysis. RESULTS: The average intensity during PLAY (73%+/-10% of
      HRmax) was significantly higher than that during WALK (57%+/-7% of HRmax,
      p=0.01). Participants spent 12.5+/-5.3 min at 80%-89% of HRmax and 5.5+/-4.6 min
      at >=90% of HRmax during PLAY, whereas intensity during WALK was <=72% of HRmax.
      The duration of PLAY was 44.3+/-0.7 min and of WALK 17.0+/-0.7 min (p=0.01). The
      relative energy expenditure during PLAY was 7.6+/-0.7 kcal/min and during WALK
      6.2+/-0.3 kcal/min (p<0.01). The enjoyment of PLAY (VAS 8.7+/-0.1) was higher
      than that of WALK (VAS 3.9+/-1.8, p=0.01). CONCLUSIONS: Exergaming can be an
      innovative way of enjoyable high-intensity training.

PMID- 29021915
TI  - Optical coherence tomography findings in methanol toxicity.
AB  - BACKGROUND: Methanol toxicity poses a significant public health problem in
      developing countries, and in Southeast Asia, where the most common source of
      poisoning is via adulterated liquor in local drinks. Methanol toxicity can have
      devastating visual consequences and retinal specialists should be aware of the
      features of this toxic optic neuropathy. The authors report a case of severe
      systemic methanol toxicity and relatively mild optic neuropathy demonstrating
      unique retinal changes on optical coherence tomography (OCT). CASE PRESENTATION:
      A previously healthy student developed ataxia, difficulty breathing and loss of
      consciousness hours after drinking homemade alcohol while traveling in Indonesia.
      She was found to have a serum pH of 6.79 and elevated methanol levels. She was
      treated with intravenous ethanol, methylprednisolone and sodium bicarbonate. When
      she awoke she had bilateral central scotomas. At presentation, she had central
      depression on visual field testing. OCT of the retinal nerve fiber layer (RNFL)
      was normal but ganglion cell layer analysis (GCL) showed highly selective loss of
      the nasal fibers in both eyes. Further, OCT of the macula demonstrated inner
      nuclear layer (INL) microcysts in the corresponding area of selective GCL loss in
      both eyes. CONCLUSIONS: The selective involvement of the papillomacular bundle
      fibers is common in toxic optic neuropathies and represents damage to the small
      caliber axons rich in mitochondria. Despite severe systemic toxicity, the
      relative sparing of the optic nerve in this case enabled characterization of the
      evolution of methanol toxicity with segmental GCL involvement and preservation of
      the RNFL, corresponding to the papillomacular bundle. This is the first reported
      case of INL microcysts in methanol optic neuropathy and supports that they are a
      non-specific finding, and may represent preferential damage to the papillomacular
      bundle.

PMID- 29021914
TI  - Retinoic acid induces white adipose tissue browning by increasing adipose
      vascularity and inducing beige adipogenesis of PDGFRalpha+ adipose progenitors.
AB  - Formation of beige adipocytes within white adipose tissue enhances energy
      expenditure, which is a promising strategy to reduce obesity and prevent
      metabolic symptoms. Vitamin A and its bioactive metabolite, retinoic acid (RA),
      have regulatory roles in lipid metabolism. Here we report that RA induces white
      adipose tissue browning via activating vascular endothelial growth factor (VEGF)
      signaling. RA triggered angiogenesis and elicited de novo generation of platelet
      derived growth factor receptor alpha positive (PDGFRalpha+) adipose precursor
      cells via VEGFA/VEGFR2 signaling. In addition, RA promoted beige/brown adipocyte
      formation from capillary networks in vitro. Using PDGFRalpha tracking mice, we
      found that the vascular system acted as an adipogenic repository by containing
      PDGFRalpha+ progenitors which differentiated into beige adipocytes under RA or
      VEGF164 treatments. Conditional knockout of VEGF receptors blocked RA-stimulated
      white adipose tissue browning. Moreover, the VEGFA and RA activated p38MAPK to
      enhance the binding of RA receptor to RA response elements of the Prdm16 promoter
      and upregulated Prdm16 transcription. In conclusion, RA induces white adipose
      tissue browning by increasing adipose vascularity and promoting beige
      adipogenesis of PDGFRalpha+ adipose progenitors.

PMID- 29021916
TI  - Vitrectomy in high myopia: a narrative review.
AB  - Pathologic myopia is associated with degenerative changes of the globe,
      especially at the posterior pole. Eyes affected by pathologic myopia have higher
      odds to undergo posterior segment surgery and, in those eyes, vitreoretinal
      surgery is challenging. Many practical tips and tricks can make the surgical
      procedures simpler, significantly preventing sight-threatening intra- and post
      operative complications. Moreover, novel surgical techniques and technological
      advancements (i.e. ad-hoc instrumentation, minimally invasive vitreoretinal
      surgery, filters, dye staining, intraoperative optical coherence tomography and 3
      dimensional surgery) may play role in highly myopic eyes. The aim of the present
      work is to review practical tips and tricks, novel surgical techniques and
      technological advancements.

PMID- 29021917
TI  - A feasibility pilot using telehealth videoconference monitoring of home-based
      NMES resistance training in persons with spinal cord injury.
AB  - INTRODUCTION: The objective of the study was to investigate the feasibility and
      initial efficacy of telehealth communication in conjunction with surface
      neuromuscular electrical stimulation (NMES) resistance training (RT) to induce
      muscle hypertrophy. MATERIALS AND METHODS: This was a home-based setting of
      within-subject control design of trained vs controlled limbs. Five men with
      chronic (>1 year postinjury) motor-complete spinal cord injury (SCI) participated
      in a twice-weekly telehealth videoconference program using home-based NMES-RT for
      8 weeks. Stimulation was applied to the knee extensor muscle group of the trained
      leg, while the untrained leg served as a control. Participants received real-time
      feedback to ensure a proper setup of electrodes and stimulator to monitor subject
      safety throughout the entire training session. Magnetic resonance imaging was
      used to measure cross-sectional areas (CSAs) and intramuscular fat (IMF) of the
      whole thigh and individual muscle groups. Average two-way travel time, distance
      traveled in miles and total cost of gas per mile were calculated. RESULTS:
      Participants had 100% compliance. Trained whole and absolute knee extensor muscle
      CSA increased by 13% (P=0.002) and 18% (P=0.0002), with no changes in the
      controlled limb. Absolute knee flexor and adductor CSAs increased by 3% (P=0.02)
      and 13% (P=0.0001), respectively. Absolute whole thigh and knee extensor IMF CSAs
      decreased significantly in the trained limb by 14% (P=0.01) and 36% (P=0.0005),
      respectively, with no changes in controlled limb. DISCUSSION: The pilot work
      documented that using telehealth communication is a safe, feasible and
      potentially cost-reducing approach for monitoring home-based NMES-RT in persons
      with chronic SCI. All trained muscles showed detectable muscle hypertrophy with
      concomitant decrease in ectopic adipose tissue.

PMID- 29021919
TI  - Safeguarding the future of independent, academic clinical cancer research in
      Europe for the benefit of patients.
AB  - Cancer is a complex disease that is constantly evolving. It is now the most
      common cause of death in Europe after cardiovascular diseases. There are
      inequalities among European countries, potentially unsustainable healthcare
      systems impacting quality of cancer care and increasing number of patients with
      cancer with rare conditions. Clinical and translational research are the backbone
      in establishing scientific advances as novel treatments and advancing progress to
      the benefit of patients. Commercially sponsored clinical trials are responsible
      for developing new medicines that can treat various disease areas, including
      cancer. It is important to note, however, that these clinical trials only assess
      the viability of compounds that are chosen by a commercial entity that funds the
      entire process. By their design and focus, these trials need to fulfil commercial
      interests and market expectations, which do not always coincide with patients'
      needs. As soon or even before novel treatments and compounds obtain formal market
      authorisation, academia will take these existing and new medicines to further
      conduct research in order to optimise their use, develop new combinations and
      with a strong focus on the patients and their needs. Established standard of care
      most commonly relies on clinical cancer research stemming from non-commercial
      entities, cooperative groups or academic clinical research. This article provides
      a consensus on the definition of academic research, illustrates its added value
      and suggests and calls to European Union institutions to support this type of
      research for the benefit of patients.

PMID- 29021918
TI  - Protection of calves by a prefusion-stabilized bovine RSV F vaccine.
AB  - Bovine respiratory syncytial virus, a major cause of respiratory disease in
      calves, is closely related to human RSV, a leading cause of respiratory disease
      in infants. Recently, promising human RSV-vaccine candidates have been engineered
      that stabilize the metastable fusion (F) glycoprotein in its prefusion state;
      however, the absence of a relevant animal model for human RSV has complicated
      assessment of these vaccine candidates. Here, we use a combination of structure
      based design, antigenic characterization, and X-ray crystallography to translate
      human RSV F stabilization into the bovine context. A "DS2" version of bovine
      respiratory syncytial virus F with subunits covalently fused, fusion peptide
      removed, and pre-fusion conformation stabilized by cavity-filling mutations and
      intra- and inter-protomer disulfides was recognized by pre-fusion-specific
      antibodies, AM14, D25, and MPE8, and elicited bovine respiratory syncytial virus
      neutralizing titers in calves >100-fold higher than those elicited by post-fusion
      F. When challenged with a heterologous bovine respiratory syncytial virus, virus
      was not detected in nasal secretions nor in respiratory tract samples of DS2
      immunized calves; by contrast bovine respiratory syncytial virus was detected in
      all post-fusion- and placebo-immunized calves. Our results demonstrate proof-of
      concept that DS2-stabilized RSV F immunogens can induce highly protective
      immunity from RSV in a native host with implications for the efficacy of
      prefusion-stabilized F vaccines in humans and for the prevention of bovine
      respiratory syncytial virus in calves.

PMID- 29021920
TI  - Vitamin D and calcium are required at the time of denosumab administration during
      osteoporosis treatment.
AB  - To evaluate the differences in outcomes of treatment with denosumab alone or
      denosumab combined with vitamin D and calcium supplementation in patients with
      primary osteoporosis. Patients were split into a denosumab monotherapy group (18
      cases) or a denosumab plus vitamin D supplementation group (combination group; 23
      cases). We measured serum bone alkaline phosphatase (BAP), tartrate-resistant
      acid phosphatase (TRACP)-5b and urinary N-terminal telopeptide of type-I collagen
      (NTX) at baseline, 1 week, as well as at 1 month and 2, 4, 8 and 12 months. We
      also measured bone mineral density (BMD) of L1-4 lumbar vertebrae (L)-BMD and
      bilateral hips (H)-BMD at baseline and at 4, 8 and 12 months. There was no
      significant difference in patient background. TRACP-5b and urinary NTX were
      significantly suppressed in both groups from 1 week to 12 months (except at 12
      months for NTX). In the combination group, TRACP-5b was significantly decreased
      compared with the denosumab monotherapy group at 2 and 4 months (P<0.05). BAP was
      significantly suppressed in both groups at 2-12 months. L-BMD significantly
      increased at 8 and 12 months (8.9%) in the combination group and at 4, 8 and 12
      months (6.0%) in the denosumab monotherapy group, compared with those before
      treatment. H-BMD was significantly increased in the combination group (3.6%)
      compared with the denosumab group (1.2%) at 12 months (P<0.05). Compared with
      denosumab monotherapy, combination therapy of denosumab with vitamin D and
      calcium stopped the decrease in calcium caused by denosumab, inhibited bone
      metabolism to a greater extent, and increased BMD (especially at the hips).

PMID- 29021921
TI  - Post-transplant lymphoproliferative disorder (PTLD): single institutional
      experience of 141 patients.
AB  - BACKGROUND: Post-transplant lymphoproliferative disorder is a well-recognized but
      rare complication of hematopoietic stem cell and solid organ transplant. Due to
      rarity of this disease, retrospective studies from major transplant centers has
      been the main source to provide treatment guidelines, which are still in
      evolution. The sample size of this study is among one of the largest study on
      PTLD till date reported throughout the world. METHODS: This study was performed
      at University of Florida which is one of the largest transplant center in South
      East United States. We performed treatment and survival analysis along with
      univariate and multivariate analysis to identify prognostic factors. RESULTS: We
      reviewed 141 patients diagnosed with PTLD over last 22 years with median follow
      up of 2.4 years. The estimated median overall survival of the entire group was
      15.0 years. Sub group analysis showed that 5-year overall survival rates of
      pediatric population were 88% (median not reached). For adults, median OS was
      5.35 years while for elderly patients it was 1.32 years. The estimated median OS
      of patients with monomorphic PTLD was 9.0 years while in polymorphic PTLD was
      19.3 years. Univariate analysis identified gender, age at transplant and PTLD
      diagnosis, performance status, IPI score, allograft type, recipient EBV status,
      multiple acute rejections prior to PTLD diagnosis, PTLD sub-type, extra-nodal
      site involvement, immunosuppressive drug regimen at diagnosis, initial treatment
      best response were statistically significant prognostic factors (p < 0.05). On
      multivariate analysis, age at PTLD diagnosis, recipient EBV status, bone marrow
      involvement, and initial best response were statistically significant prognostic
      factors (p < 0.05). Surprisingly, use of Rituximab alone as upfront therapy had
      poor hazard ratio in the cumulative group as well less aggressive PTLD subgroup
      comprising of early lesions and polymorphic PTLD. CONCLUSIONS: Our experience
      with treatment and analysis of outcomes does challenge current role of Rituximab
      use in treatment of PTLD. Currently as we define role of immunotherapy in cancer
      treatment, the role of acute rejections and immunosuppressant in PTLD becomes
      more relevant as noticed in our study. This study was also able to find new
      prognostic factors and also verified other known prognostic factors.

PMID- 29021922
TI  - Texture Feature Variability in Ultrasound Video of the Atherosclerotic Carotid
      Plaque.
AB  - The objective of this paper was to investigate texture feature variability in
      ultrasound video of the carotid artery during the cardiac cycle in an attempt to
      define new discriminatory biomarkers of the vulnerable plaque. More specifically,
      in this paper, 120 longitudinal ultrasound videos, acquired from 40 normal (N)
      subjects from the common carotid artery and 40 asymptomatic (A) and 40
      symptomatic (S) subjects from the proximal internal carotid artery were
      investigated. The videos were intensity normalized and despeckled, and the intima
      media complex (IMC) (from the N subjects) and the atherosclerotic carotid plaques
      (from the A and S subjects) were segmented from each video, in order to extract
      the M-mode image, and the texture features associated with cardiac states of
      systole and diastole. The main results of this paper can be summarized as
      follows: 1) texture features varied significantly throughout the cardiac cycle
      with significant differences identified between the cardiac systolic and cardiac
      diastolic states; 2) gray scale median was significantly higher at cardiac
      systole versus diastole for the N, A, and S groups investigated; 3) plaque
      texture features extracted during the cardiac cycle at the systolic and diastolic
      states were statistically significantly different between A and S subjects (and
      can thus be used to discriminate between A and S subjects successfully). The
      combination of systolic and diastolic features yields better performance than
      those alone. It is anticipated that the proposed system may aid the physician in
      clinical practice in classifying between N, A, and S subjects using texture
      features extracted from ultrasound videos of IMC and carotid artery plaque.
      However, further evaluation has to be carried out with more videos and additional
      features.

PMID- 29021923
TI  - Toward a Personalized Real-Time Diagnosis in Neonatal Seizure Detection.
AB  - The problem of creating a personalized seizure detection algorithm for newborns
      is tackled in this paper. A probabilistic framework for semi-supervised
      adaptation of a generic patient-independent neonatal seizure detector is
      proposed. A system that is based on a combination of patient-adaptive
      (generative) and patient-independent (discriminative) classifiers is designed and
      evaluated on a large database of unedited continuous multichannel neonatal EEG
      recordings of over 800 h in duration. It is shown that an improvement in the
      detection of neonatal seizures over the course of long EEG recordings is
      achievable with on-the-fly incorporation of patient-specific EEG characteristics.
      In the clinical setting, the employment of the developed system will maintain a
      seizure detection rate at 70% while halving the number of false detections per
      hour, from 0.4 to 0.2 FD/h. This is the first study to propose the use of online
      adaptation without clinical labels, to build a personalized diagnostic system for
      the detection of neonatal seizures.

PMID- 29021924
TI  - Large Unilateral Adrenal Mass with Surrounding Brown Fat: A Case Report.
AB  - Pheochromocytomas are rare tumors derived from chromaffin cells located in the
      adrenal and extra adrenal tissues. Pheochromocytomas are diagnosed biochemically
      and localized using different imaging modalities. The definitive management is
      surgical resection. Brown adipose tissues are normally present during fetal
      development, with regression over time. Brown adipose tissues are thermogenic and
      usually located in the neck, mediastinum, and retroperitoneum. Here, we report a
      case of a unilateral pheochromocytoma surrounded by brown fat. The abnormal
      stimulation of brown fat noted on positive emission tomography scan (PET)
      resolved after the pheochromocytoma was resected.

PMID- 29021925
TI  - Acetazolamide: Treatment of Psychogenic Polydipsia.
AB  - We are reporting a case of psychogenic polydipsia from a State of Ohio
      psychiatric hospital. The patient has a known five-year history of psychogenic
      polydipsia with recurrent hyponatremia and has been diagnosed with
      schizoaffective disorder bipolar type 1, according to the Diagnostic and
      Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, for the
      past two decades. There was a marked improvement with the use of acetazolamide,
      resulting in a decreased compulsion to drink fluid and improvement of his
      hyponatremia. The patient was observed for six months. We evaluated the water
      balance of the patient with diurnal weight measurements (DWG) and a weekly
      comprehensive metabolic panel (CMP) to monitor Na+ levels. His symptoms and
      hyponatremia were improved with acetazolamide. The treatment was well tolerated
      without any adverse effects and improved his quality of life.

PMID- 29021926
TI  - Enigma of Extrapulmonary Tuberculosis: Where Do We Stand?
AB  - Tuberculosis remains a worldwide public health concern. Atypical extrapulmonary
      presentations may delay its diagnosis and treatment. The present study
      illustrates the importance of ruling out extrapulmonary tuberculosis in patients
      presenting with nonspecific symptoms of abdominal diseases. Furthermore, we
      discuss the variety of clinical presentations, diagnostic challenges, current
      therapeutic protocols, and prognostic factors associated with extrapulmonary
      tuberculosis. Early diagnosis and effective treatment may decrease morbidity and
      mortality in such patients.

PMID- 29021927
TI  - Split Femoral Nerve Due to Psoas Tertius Muscle: A Review with Other Cases of
      Variant Muscles Traversing the Femoral Nerve.
AB  - Leg pain from lumbar disc herniation is a common presentation. However, certain
      muscular and peripheral nerve variants may present similarly and represent an
      unrecognized etiology of femoral nerve dysfunction. Such cases might affect the
      outcome of specific treatment regimes. Therefore, recognition of these variations
      in anatomy may be useful to the clinician when treating the patient with
      medically refractory lower limb pain. Some reports have reported variant slips of
      the psoas and iliacus muscles, which may split the femoral nerve causing a
      potential risk for nerve entrapment. Herein, we report a very unusual variant of
      the psoas muscles, the psoas tertius, which pierced the femoral nerve into two
      parts. Additionally, the literature of other similar muscle variants is reviewed.
      Clinicians should be aware of anatomical muscular variants of the posterior
      abdominal wall and the propensity of such anomalies to result in distortion of
      regional neural structures. In this regard, the anatomy of the psoas tertius
      should be known.

PMID- 29021928
TI  - Bravo(r) Capsule Aspiration: A Rare Case Report.
AB  - Bravo(r) capsule (BC) (Medtronic, Minneapolis, MN) endoscopy is a reliable,
      viable, and well-tolerated diagnostic modality for resistant gastroesophageal
      reflux disease (GERD). Common complications of the procedure include early
      dislodgment, poor transmission, and premature removal due to intractable pain,
      while aspiration of the capsule is exceedingly rare. This paper reports a case of
      BC aspiration in a 52-year-old female who presented after being ventilated when
      her oxygen saturation dropped. The initial chest radiograph revealed that the BC
      was in the right main bronchus; the site was further elaborated by flexible
      endoscopy and the capsule was found to be in the right lower lobe bronchus distal
      to the bronchus intermedius. This was followed by a rigid bronchoscopy and
      extraction of the capsule with rigid grasper forceps. Although this occurs
      rarely, immediate endotracheal intubation and ventilator support is the preferred
      emergency step in such cases until bronchoscopic removal can be performed.

PMID- 29021929
TI  - Rare Presentation of a Posterior Mediastinal Cystic Schwannoma as a Large Pleural
      Effusion.
AB  - A 46-year-old man presented with shortness of breath and recurrent, left-sided
      pleural effusions. A computed tomography (CT) scan of the chest showed a large,
      left-sided pleural effusion with a mass in the posterior mediastinum. A pleural
      tap showed lymphocytic exudate. The biopsy of the mass was inconclusive. A left
      posterolateral thoracotomy was performed, which showed a large posterior
      mediastinal mass adherent to the left lung. The mass was completely excised and
      the histopathology proved it to be giant predominantly cystic schwannoma. The
      pleural effusion resolved after tumor resection.

PMID- 29021930
TI  - Computer-Assisted Learning Applications in Health Educational Informatics: A
      Review.
AB  - Computer-assisted learning (CAL) as a health informatics application is a useful
      tool for medical students in the era of expansive knowledge bases and the
      increasing need for and the consumption of automated and interactive systems. As
      the scope and breadth of medical knowledge expand, the need for additional
      learning outside of lecture hours is becoming increasingly important. CAL can be
      an impactful adjunct to conventional methods that currently exist in the halls of
      learning. There is an increasing body of literature that suggests that CAL should
      be a commonplace and the recommended method of learning for medical students.
      Factors such as technical issues that hinder the performance of CAL are also
      evaluated. We conclude by encouraging the use of CAL by medical students as a
      highly beneficial method of learning that complements and enhances lectures and
      provides intuitive, interactive modulation of a self-paced curriculum based on
      the individual's academic abilities.

PMID- 29021931
TI  - In-silico combinatorial design and pharmacophore modeling of potent antimalarial
      4-anilinoquinolines utilizing QSAR and computed descriptors.
AB  - There are very few studies for combinatorial library design and high throughput
      screening of 4-anilinoquinoline antimalarial compounds having activities against
      parasitic strain of P. falciparum. Therefore, an attempt has been made in the
      present paper to design potent lead compounds in this congener utilizing
      quantitative structure activity relationship utilizing theoretical molecular
      descriptors. QSAR models for a series of 4-anilinoquinolines considering various
      theoretical molecular descriptors including topological, constitutional,
      geometrical, functional group and atom-centered fragments has been carried out by
      stepwise forward-backward variable selections assimilating multiple linear
      regression (MLR) methods showing the topological indices contribute maximum
      impact on parasitic P. falciparum strain. A combinatorial library of 2160
      compounds has been generated and finally, 16 compounds were screened through high
      throughput screening as promising 4-anilinoquinoline antimalarial hits based on
      their predicted activities utilizing topological descriptor based validated QSAR
      model. Highly predicted active compounds were then undergone for pharmacophore
      modeling to predict mode of binding and to optimize leads having greater affinity
      towards malarial P. falciparum parasitic strain.

PMID- 29021932
TI  - An Evaluation of Lag Schedules of Reinforcement During Functional Communication
      Training: Effects on Varied Mand Responding and Challenging Behavior.
AB  - We evaluated the effects of lag schedules of reinforcement during functional
      communication training (FCT) on the varied use of mands and challenging behavior
      by two individuals diagnosed with autism. Specifically, we compared the effects
      of Lag 0 and Lag 1 schedules of reinforcement during FCT. The results showed that
      each participant exhibited increases in varied mand responding during FCT with
      the Lag 1 schedule of reinforcement relative to Lag 0; challenging behavior
      remained low during both FCT lag conditions relative to baseline. Results are
      discussed in terms of treatment implications relating to FCT and the potential
      prevention and/or mitigation of clinical relapse during challenges to treatment.

PMID- 29021933
TI  - A Survey-Based Method to Evaluate Optimal Treatment Selection for Escape
      Maintained Problem Behavior.
AB  - Geiger, Carr, and LeBlanc (2010) developed a decision-making model for escape
      maintained problem behavior that could be used to guide the course of treatment
      selection. We used a digital survey to evaluate the model's potential usefulness.
      We presented novice and expert practitioners' written hypothetical scenarios and
      asked them to determine the optimal treatment in a given situation. Some
      participants were given the model, whereas others were instructed to use their
      best clinical judgment. Using logistic regression analyses, the general findings
      for our scenarios were the following: (a) experts without the aid of a decision
      model had better odds of selecting the optimal treatment than novices without the
      decision model, (b) experts with the decision model did not have greater odds of
      selecting optimal treatment than experts without the model, and

PMID- 29021934
TI  - The Effects of Bug-in-Ear Coaching on Pre-Service Behavior Analysts' Use of
      Functional Communication Training.
AB  - Behavior analysts play an important role in supporting the behavior and learning
      of young children with disabilities in natural settings. However, there is very
      little research related specifically to developing the skills and competencies
      needed by pre-service behavior analysts. This study examined the effects of "bug
      in-ear" (BIE) coaching on pre-service behavior analysts' implementation of
      functional communication training with pre-school children with autism in their
      classrooms. BIE coaching was associated with increases in the rate of functional
      communication training trials each intern initiated per session and in the
      fidelity with which interns implemented functional communication training. Adults
      created more intentional opportunities for children to communicate, and adults
      provided more systematic instruction around those opportunities.

PMID- 29021935
TI  - Preliminary Evidence on the Efficacy of Mindfulness Combined with Traditional
      Classroom Management Strategies.
AB  - The current case study combined mindfulness-based strategies with a classroom
      behavior management treatment package, to assist teachers with managing 3rd grade
      student behaviors. Two teachers (Classroom teacher and Specials teacher) and six
      students within the same classroom were observed using a 5-min momentary time
      sampling procedure. A delayed multiple baseline across settings (e.g., Classroom
      teacher, Specials teacher) design was used to assess student behaviors across
      baseline (A), classroom behavior management treatment package (CBM) (B), CBM plus
      mindfulness (C), and CBM plus mindfulness and self-monitoring (D). Behavioral
      treatment alone increased on-task behaviors for four of six (66%) students
      compared to baseline; however, five of six (83%) students increased and sustained
      high rates of on-task behaviors when mindfulness exercises were added to the
      behavior analytic techniques. These preliminary results support the combination
      of mindfulness-based strategies with traditional behavior analytic interventions
      for increasing student on-task behaviors in classroom settings.

PMID- 29021936
TI  - Utilizing PEAK Relational Training System to Teach Visual, Gustatory, and
      Auditory Relations to Adults with Developmental Disabilities.
AB  - Two multiple baseline designs were conducted across participants to determine if
      the promoting the emergence of advanced knowledge (PEAK) equivalence module was
      an effective tool in teaching adults with autism relationships between stimuli.
      More specifically, a transitivity program utilizing the gustatory sensory
      modality was implemented. Stimuli were selected and probed initially preceding
      the training. First, gustatory stimuli to a visual picture were trained. Then, a
      visual picture to a spoken word was trained. Finally, once mastery criterion was
      reached, each participant's responding was tested to determine whether there were
      derived relations following training. Results showed that all three participants
      reached mastery criterion in training sessions and were able to derive new
      relations without direct training.

PMID- 29021937
TI  - Recommendations for Identifying Sleep Problems and Treatment Resources for
      Children with Autism Spectrum Disorder.
AB  - Many young children experience sleep problems that may influence their daytime
      functioning. These sleep problems are especially prevalent in young children with
      autism spectrum disorder (ASD). Therefore, general recommendations for
      identifying and treating sleep problems in children with ASD are needed for
      behavior analysts to identify potential sleep problems and make empirically
      informed decisions regarding treatment options. The current paper seeks to
      provide behavior analysts, who work with children with ASD, with informative
      research on pediatric sleep problems, sleep measures, and options for behavioral
      sleep treatment.

PMID- 29021939
TI  - Automating Phase Change Lines and Their Labels Using Microsoft Excel(R).
AB  - Many researchers have rallied against drawn in graphical elements and offered
      ways to avoid them, especially regarding the insertion of phase change lines
      (Deochand, Costello, & Fuqua, 2015; Dubuque, 2015; Vanselow & Bourret, 2012).
      However, few have offered a solution to automating the phase labels, which are
      often utilized in behavior analytic graphical displays (Deochand et al., 2015).
      Despite the fact that Microsoft Excel(r) is extensively utilized by behavior
      analysts, solutions to resolve issues in our graphing practices are not always
      apparent or user-friendly. Considering the insertion of phase change lines and
      their labels constitute a repetitious and laborious endeavor, any minimization in
      the steps to accomplish these graphical elements could offer substantial time
      savings to the field. The purpose of this report is to provide an updated way
      (and templates in the supplemental materials) to add phase change lines with
      their respective labels, which stay embedded to the graph when they are moved or
      updated.

PMID- 29021938
TI  - Are Brazilian Behavior Analysts Publishing Outside the Box? A Survey of General
      Science Media.
AB  - Recent studies have stressed the importance of disseminating behavior analysis to
      a more diverse audience and have provided ways to do so effectively. General
      science publications offer an attractive venue for communicating with a
      scientifically educated public. The present study examines behavior analysis
      research published in Science Today and Research Fapesp, monthly general science
      publications published by the Brazilian Society for the Advancement of Science
      and Sao Paulo Research Foundation, respectively. Behavior analytic terms were
      searched in issues published from 2003 to 2014, along with psychoanalytic terms
      as a comparative measure. Only 13 behavior analysis articles were found, while
      psychoanalytic articles totaled 150. Six of the behavior analysis articles
      misconstrue fundamental concepts of behavior analysis. The study recommends that
      behavior analysis researchers extend the dissemination of their findings outside
      the box.

PMID- 29021940
TI  - Using Video to Bridge the Gap Between Problem Behavior and a Delayed Time-out
      Procedure.
AB  - Treatment plans focused on problem behavior often include punishment
      contingencies to decrease problem behavior. Immediate punishers are typically
      more effective than delayed punishers, but immediate delivery of a punisher is
      not always possible. Strategies need to be developed to increase the suppressive
      effects of delayed punishers. This study demonstrated the effectiveness of a
      treatment package involving replaying a video recording of problem behavior
      immediately before delivering a 15 min delayed time-out. This treatment package
      may prove to be an accessible and inexpensive strategy when using delayed
      punishers.

PMID- 29021941
TI  - An Evaluation of Differential Observing Responses During Receptive Label
      Training.
AB  - The current study compared the use of a differential observing response (DOR)
      during receptive label training to a condition without the DOR. We extended the
      research on DORs used during receptive label training by using them with
      progressive prompt delay procedures and assessing responding following mastery
      without the DOR. Results indicated that both participants performed better in the
      DOR condition during the first comparison, but results were less clear in the
      second comparison.

PMID- 29021942
TI  - Improving Pre-Service Teachers' Performance Skills Through Behavioral Skills
      Training.
AB  - In higher education, instruction that incorporates effective performance skills
      training is vital to equipping pre-service teachers with the tools they will use
      to educate children. This study evaluated the effects of behavioral skills
      training (BST) on performance of evidence-based practices by undergraduate pre
      service special education teachers. A pre-post design was used to evaluate
      performance during role-play. BST sessions produced higher levels of correct
      performance than baseline measures across all seven participants. We discuss
      limitations of these results with suggestions for future research, along with
      recommendations for incorporating BST into university settings.

PMID- 29021943
TI  - Application of a Pyramidal Training Model on the Implementation of Trial-Based
      Functional Analysis: a Partial Replication.
AB  - We employed a pyramidal training model (PTM) to teach staff to correctly
      implement and collect data for trial-based functional analysis (TBFA) in
      simulated situations. First, we trained four behavioral consultants (BCs) in a
      group format, who each trained one behavior technician (BT) in an individual
      format. We utilized a non-concurrent multiple baseline design to evaluate the
      effect of the training. During generalization probes, participants implemented
      TBFA with a novel problem behavior. This study will contribute to the literature
      on teaching staff how to conduct TBFA. This study demonstrates the application of
      a two-level PTM. This study illustrates how agencies can utilize the Task
      Analysis Training Protocol within a PTM to train staff on implementation of TBFA.

PMID- 29021944
TI  - A Program Evaluation of Home and Center-Based Treatment for Autism Spectrum
      Disorder.
AB  - The present study aimed to retrospectively compare the relative rates of mastery
      of exemplars for individuals with ASD (N = 313) who received home-based and
      center-based services. A between-group analysis found that participants mastered
      significantly more exemplars per hour when receiving center-based services than
      home-based services. Likewise, a paired-sample analysis found that participants
      who received both home and center-based services had mastered 100 % more per hour
      while at the center than at home. These analyses indicated that participants
      demonstrated higher rates of learning during treatment that was provided in a
      center setting than in the participant's home.

PMID- 29021945
TI  - An Evaluation of Instructive Feedback to Teach Play Behavior to a Child with
      Autism Spectrum Disorder.
AB  - Instructive feedback is used to expose learners to secondary targets during skill
      acquisition programs (Reichow & Wolery, in Journal of Applied Behavior Analysis,
      44, 327-340, 2011; Werts, Wolery, Gast, & Holcombe, in Journal of Behavioral
      Education, 5, 55-75, 1995). Although unrelated feedback may have clinical utility
      in practice, very little research has evaluated unrelated instructive feedback,
      particularly for promoting play behavior (Colozzi, Ward, & Crotty, in Education
      and Training in Developmental Disabilities, 43, 226-248, 2008). The purpose of
      the study was to determine if play emerged after embedding instructive feedback
      during the consequence portion of discrete trial training to teach tacts. An
      adapted alternating treatments design was used to compare tact training with and
      without instructive feedback for play behaviors. Instructive feedback resulted in
      the emergence of play behaviors during tabletop instruction and a play area of a
      classroom. We discuss the results in terms of clinical practice and future
      research.

PMID- 29021946
TI  - Predictors of pneumococcal carriage and the effect of the 13-valent pneumococcal
      conjugate vaccination in the Western Australian Aboriginal population.
AB  - BACKGROUND: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced to
      prevent invasive pneumococcal disease (IPD) in Western Australian (WA) Aboriginal
      people in 2001. PCV13 replaced PCV7 in July 2011, covering six additional
      pneumococcal serotypes; however, IPD rates remained high in Aboriginal people in
      WA. Upper respiratory tract pneumococcal carriage can precede IPD, and PCVs alter
      serotype distribution. METHODS: To assess the impact of PCV13 introduction,
      identify emerging serotypes, and assess risk factors for carriage, nasopharyngeal
      swabs and information on demographic characteristics, health, medication and
      living conditions from Aboriginal children and adults across WA from August 2008
      to November 2014 were collected. Bacteria were cultured using selective media and
      pneumococcal isolates were serotyped by Quellung reaction. Risk factors were
      analysed by multivariable logistic regression. RESULTS: One thousand five hundred
      swabs pre- and 1385 swabs post-PCV13 introduction were collected. Pneumococcal
      carriage was detected in 66.8% of children <5 years old and 53.2% of 5-14 year
      olds post-PCV13, compared with pre-PCV13 prevalence of 72.2% and 49.4%,
      respectively. The prevalence of PCV13-non-PCV7 serotypes decreased in children <5
      years old from 13.5% pre-PCV13 to 5.8% post-PCV13 (p < 0.01), and from 8.4% to
      6.1% in children 5-14 years old (p > 0.05). The most common serotypes post-PCV13
      were 11A (prevalence 4.0%), 15B (3.5%), 16F (3.5%), and 19F (3.2%). Risk of
      detection of pneumococcal carriage increased until age 12 months (odds ratio [OR]
      4.19, 95% confidence interval [CI] 2.39-7.33), with nasal discharge (OR 2.49 [95%
      CI 2.00-3.09]), residence in a remote community (OR 2.21 [95% CI 1.67-2.92]) and
      household crowding (OR 1.36 [95% CI 1.11-1.67]). Recent antibiotic use was
      negatively associated with pneumococcal carriage (OR 0.48 [95% CI 0.33-0.69]).
      Complete resistance to penicillin was present among isolates of serotypes 19A
      (6.0%), 19F (2.3%) and non-serotypeable isolates (1.9%). Serotype 23F and newly
      emerged serotype 7B isolates showed high rates of resistance to cotrimoxazole,
      erythromycin and tetracycline (86.9%, 86.9%, 82.0%, respectively for 23F, 100.0%,
      100.0% and 93.3% for 7B). CONCLUSION: Since PCV13 replaced PCV7, carriage of
      PCV13-non-PCV7 serotypes decreased significantly among children <5 years old,
      those most likely to have received PCV13, and to a lesser extent in older people.
      Known risk factors for carriage including crowding and young age remain in the
      Aboriginal population.

PMID- 29021947
TI  - Health symptoms in residents living near shale gas activity: A retrospective
      record review from the Environmental Health Project.
AB  - Increasing evidence demonstrates an association between health symptoms and
      exposure to unconventional natural gas development (UNGD). The purpose of this
      study is to describe the health of adults in communities with intense UNGD who
      presented for evaluation of symptoms. Records of 135 structured health
      assessments conducted between February 2012 and October 2015 were reviewed
      retrospectively. Publicly available data were used to determine proximity to gas
      wells. Analysis was restricted to records of adults who lived within 1 km of a
      well in Pennsylvania and denied employment in the gas industry (n = 51). Symptoms
      in each record were reviewed by a physician. Symptoms that could be explained by
      pre-existing or concurrent conditions or social history and those that began or
      worsened prior to exposure were excluded. Exposure was calculated using date of
      well drilling within 1 km. The number of symptoms/participant ranged from 0 to 19
      (mean = 6.2; SD = 5.1). Symptoms most commonly reported were: sleep disruption,
      headache, throat irritation, stress or anxiety, cough, shortness of breath, sinus
      problems, fatigue, nausea, and wheezing. These results are consistent with
      findings of prior studies using self-report without physician review. In
      comparison, our results are strengthened by the collection of health data by a
      health care provider, critical review of symptoms for possible alternative
      causes, and confirmation of timing of exposure to unconventional natural gas well
      relative to symptom onset or exacerbation. Our findings confirm earlier studies
      and add to the growing body of evidence of the association between symptoms and
      exposure to UNGD.

PMID- 29021948
TI  - The association between distance to public amenities and cardiovascular risk
      factors among lower income Singaporeans.
AB  - Existing evidence on the association between built environment and cardiovascular
      disease (CVD) risk factors focused on the general population, which may not
      generalize to higher risk subgroups such as those with lower socio-economic
      status (SES). We examined the associations between distance to 5 public amenities
      from residential housing (public polyclinic, subsidized private clinic, healthier
      eatery, public park and train station) and 12 CVD risk factors (physical
      inactivity, medical histories and unhealthy dietary habits) among a study sample
      of low income Singaporeans aged >= 40 years (N = 1972). Using data from the
      Singapore Heart Foundation Health Mapping Exercise 2013-2015, we performed a
      series of logistic mixed effect regressions, accounting for clustering of
      respondents in residential blocks and multiple comparisons. Each regression
      analysis used the minimum distance (in km) between residential housing and each
      public amenity as an independent continuous variable and a single risk factor as
      the dependent variable, controlling for demographic characteristics. Increased
      distance (geographical inaccessibility) to a train station was significantly
      associated with lower odds of participation in sports whereas greater distance to
      a subsidized private clinic was associated with lower odds of having high
      cholesterol diagnosed. Increasing distance to park was positively associated with
      higher odds of less vegetable and fruits consumption, deep fried food and fast
      food consumption in the preceding week/month, high BMI at screening and history
      of diabetes, albeit not achieving statistical significance. Our findings
      highlighted potential effects of health-promoting amenities on CVD risk factors
      in urban low-income setting, suggesting gaps for further investigations.

PMID- 29021949
TI  - Correlates of unsuccessful smoking cessation among adults in Bangladesh.
AB  - Having 21.9 million adult smokers, Bangladesh ranks among the top ten heaviest
      smoking countries in the world. Correlates of unsuccessful smoking cessation
      remain unknown. We aimed to identify the correlates of unsuccessful smoking
      cessation among adults in Bangladesh. We used data from the 2009 Global Adult
      Tobacco Survey (GATS) for Bangladesh. We compared socio-demographic, belief about
      health effect of smoking, and environmental characteristics of current smokers
      who had a recent failed quit attempt during the past 12 months of the survey
      (unsuccessful quitters) with those former smokers who had quit >= 12 months
      earlier of the survey and had not relapsed (successful quitters). Data were
      analyzed using logistic regression model and generalized estimating equations. A
      total of 1552 smokers (1058 unsuccessful quitters and 494 successful quitters)
      aged 15 years and older who participated in the survey was included in this
      study. Among the smokers, 1058 (68%) were unsuccessful quitters. Our analysis
      showed that older aged, female, and higher educated smokers were less likely to
      quit unsuccessfully. Moreover, who believed that smoking causes serious illness
      were also less likely to quit unsuccessfully. For the interaction between place
      of residence and smoking rules inside home, we found that among the smoker's, in
      those house smoking was allowed, and who lived in urban place were less likely to
      be unsuccessful in quitting than those who lived in rural place. Our findings
      suggest a cessation program that requires integrated approach with a view to
      considering these findings in setting up.

PMID- 29021950
TI  - Population levels of, and inequalities in, active travel: A national, cross
      sectional study of adults in Scotland.
AB  - This study aimed to describe active travel (walking or cycling) in Scotland and
      explore potential demographic, geographic, and socio-economic inequalities in
      active travel. We extracted data for the period 2012-13 (39,585 journey stages)
      from the Scottish Household Survey. Survey travel diaries recorded all journeys
      made on the previous day by sampled individuals aged 16 + living within Scotland,
      and the stages within each journey. Descriptive statistics were calculated for
      journey stages, mode, purpose and distance. Logistic regression models were
      fitted to examine the relationship between the likelihood of a journey stage
      being active, age, sex, area deprivation and urban/rural classification. A
      quarter of all journey stages were walked or cycled (26%, n: 10,280/39,585); 96%
      of these were walked. Those living in the least deprived areas travelled a
      greater average distance per active journey stage than those in the most
      deprived. The likelihood of an active journey stage was higher for those living
      in the most deprived areas than for those in the least deprived (Odds Ratio (OR)
      1.21, 95% CI 1.04-1.41) and for those in younger compared to older age groups (OR
      0.44, 95% CI 0.34-0.58). In conclusion, socio-economic inequalities in active
      travel were identified, but - contrary to the trends for many health-beneficial
      behaviours - with a greater likelihood of active travel in more deprived areas.
      This indicates a potential contribution to protecting and improving health for
      those whose health status tends to be worse. Walking was the most common mode of
      active travel, and should be promoted as much as cycling.

PMID- 29021951
TI  - Marrow signal mimicking tumor on MRI T1-weighted imaging after neoadjuvant
      chemotherapy in extremity osteosarcomas.
AB  - PURPOSE: Many studies had demonstrated that MRI T1-weighted imaging was the most
      accurate method to evaluate the intramedullary extent of extremity osteosarcoma.
      However, we found that after neoadjuvant chemotherapy new low signal of MRI T1
      imaging was detected near tumor, which mimicked the tumor progression. The aim of
      this study was to describe the incidence and type of this new signal, to reveal
      the pathological correlation with this imaging change. METHODS: We included 74
      extremity osteosarcomas managed between June 2011 and November 2012 in this
      retrospective study. The T1-weighted MRI images of the affected extremity before
      and after neoadjuvant chemotherapy were reviewed and compared. The subjects were
      then classified according to the appearance of the border between the area
      involved by osteosarcoma and the normal marrow with attention paid to whether the
      border was continuous and the width of the zone of transition. The study
      population was classified into one of four classifications: 'clear', 'continuous
      diffuse', 'discontinuous island-like' and 'discontinuous diffuse'. 11 patients
      underwent MRI of bilateral extremities, and for these patients we assessed the
      appearance of the uninvolved extremity with that with osteosarcoma. Following
      surgical resection of the tumor, the pathologic appearance was compared with the
      pre-operative MRI findings. RESULTS: According to our classification system, all
      74 subjects were 'clear' before neoadjuvant chemotherapy. After neoadjuvant
      chemotherapy, 30 subjects (40.5%) were still clear. Of the 44 subjects (59.5%)
      not classified as 'clear', 22 (29.7%) were classified as 'continuous diffuse', 4
      (5.4%) as 'discontinuous island-like', and 18 (24.3%) as 'discontinuous diffuse'.
      Of the subjects with MRI of bilateral femurs, no radiologic difference was noted
      in the normal marrow bilaterally. No significant difference in overall survival
      and relapse free survival was noted between patients grouped according to the
      subtypes of MRI noted. CONCLUSIONS: Neoadjuvant chemotherapy for extremity
      osteosarcoma can result in a variety of changes of the MRI appearance of tumor
      and adjacent bone and marrow. Areas of signal change beyond the tumor that
      represent marrow conversion and not tumor progression appear on T1 weighted
      imaging to be lower in signal than subcutaneous fat and higher in signal than
      muscle. Recognizing the existence of the effect of neoadjuvant chemotherapy on
      the MR appearance of the tumor and surrounding bone and myeloid elements is
      important so as to plan for oncological sound tumor resections while avoiding
      resecting more normal bone than necessary.

PMID- 29021952
TI  - The forgotten view: Chest X-ray - Lateral view.
AB  - With CT (computed tomography) chest gaining more importance as a diagnostic tool,
      chest X-ray especially the lateral view is taken less commonly nowadays. Besides
      CT chest is also proven to be superior to chest X-ray in patients with major
      blunt trauma. We are presenting a 68-year old male who was partially treated from
      outside for a left sided pneumonia. He came to our hospital because of persisting
      chest pain. Chest X-ray, frontal view (postero-anterior) was almost normal except
      for a mild opacity in the left lower zone. CT scan of the chest revealed a fluid
      collection posteriorly enclosed within enhancing pleura. Chest X-ray, left
      lateral view showed a corresponding posterior pleural based opacity. We are
      presenting this case to highlight the importance of the lateral view of the chest
      X-ray. In selected cases there is still a role for the lateral view. With the
      three dimensional visualization provided by the CT, the lateral view of the chest
      may be easier to understand. Consequent to the initial diagnosis by CT further
      follow up can be done with the chest X-ray. In a limited way this mitigates
      unnecessary expenditure and more importantly prevents the patient from exposure
      to harmful radiation in the form of repeated CT.

PMID- 29021953
TI  - Bilateral lung disease, extensive and diffuse. Diagnosis of pulmonary alveolar
      proteinosis by bronchoscopic cryobiopsy.
AB  - Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the intra
      alveolar accumulation of a proteinaceous phospholipid-laden material called
      surfactant. Clinically, this disease should be suspected with respiratory failure
      in association with a crazy paving pattern on high-resolution chest computed
      tomography. We report a 24-year-old gentleman who was referred to us for a
      history of respiratory failure, treatment with invasive ventilation and
      tracheostomy. His blood exams and biochemistry were normal. His infectious and
      rheumatological panel was negative for a secondary disease. A flexible
      bronchoscopy with a transbronchial biopsy through a CryoProbe was performed. An
      anatomopathological analysis was periodic acid-Schiff positive for PAP. A
      CryoProbe is a recently developed diagnostic tool that improves the diagnostic
      yield in diffuse lung diseases compared to bronchoscopy with transbronchial
      biopsy. This method should be considered for patients with diffuse lung disease
      and PAP.

PMID- 29021954
TI  - Continous Rituximab treatment for recurrent diffuse alveolar hemorrhage in a
      patient with systemic lupus erythematosus and antiphosholipid syndrome.
AB  - Diffuse alveolar hemorrhage (DAH) is a rare but potentially fatal complication in
      systemic lupus erythematosus (SLE). DAH is typically characterized by hemoptysis,
      dyspnea, new infiltrates on chest x-rays or CT-scans and a drop in hemoglobin.
      DAH is seen in less than 2% of patients with SLE and carries a high acute
      mortality risk of up to 70-90%. The current treatment of DAH is high-dose
      intravenous corticosteroids, cyclophosphamide and extensive supportive care.
      Plasmapheresis is also often considered in the treatment. A few case reports have
      described patients with SLE and DAH in whom a single series of Rituximab (RTX), a
      specific anti-CD20-antigen B-cell antibody, successfully has been used to treat
      DAH. We here present the first case of a patient with combined SLE,
      antiphospholipid syndrome (APS) and recurrent DAH who was successfully controlled
      by continued treatment with RTX.

PMID- 29021955
TI  - When Christmas decoration goes hand in hand with bronchial aspiration ....
AB  - We report the case of a 14-month-old girl suffering from cough and wheeze around
      Christmas. She was treated with anti-asthmatic drugs with no success, and 3 weeks
      later a chest X-ray revealed a LED bulb in the left main bronchus. This LED bulb
      came from a Christmas light garland decorating the Christmas tree. We discuss the
      different Christmas objects that can be inhaled by young children, the challenge
      to diagnose bronchial inhalation during this winter period, and the emergence of
      new foreign bodies, such as LED bulbs, with a particularly aerodynamic shape.

PMID- 29021957
TI  - Whole genome shotgun sequencing of Indian strains of Streptococcus agalactiae.
AB  - Group B streptococcus is known as a leading cause of neonatal infections in
      developing countries. The present study describes the whole genome shotgun
      sequences of four Group B Streptococcus (GBS) isolates. Molecular data on
      clonality is lacking for GBS in India. The present genome report will add
      important information on the scarce genome data of GBS and will help in deriving
      comparative genome studies of GBS isolates at global level. This Whole Genome
      Shotgun project has been deposited at DDBJ/ENA/GenBank under the accession
      numbers NHPL00000000 - NHPO00000000.

PMID- 29021956
TI  - Grey and white matter differences in Chronic Fatigue Syndrome - A voxel-based
      morphometry study.
AB  - OBJECTIVE: Investigate global and regional grey and white matter volumes in
      patients with Chronic Fatigue Syndrome (CFS) using magnetic resonance imaging
      (MRI) and recent voxel-based morphometry (VBM) methods. METHODS: Forty-two
      patients with CFS and thirty healthy volunteers were scanned on a 3-Tesla MRI
      scanner. Anatomical MRI scans were segmented, normalized and submitted to a VBM
      analysis using randomisation methods. Group differences were identified in
      overall segment volumes and voxel-wise in spatially normalized grey matter (GM)
      and white matter (WM) segments. RESULTS: Accounting for total intracranial
      volume, patients had larger GM volume and lower WM volume. The voxel-wise
      analysis showed increased GM volume in several structures including the amygdala
      and insula in the patient group. Reductions in WM volume in the patient group
      were seen primarily in the midbrain, pons and right temporal lobe. CONCLUSION:
      Elevated GM volume in CFS is seen in areas related to processing of interoceptive
      signals and stress. Reduced WM volume in the patient group partially supports
      earlier findings of WM abnormalities in regions of the midbrain and brainstem.

PMID- 29021958
TI  - Complete mitochondrial genome sequence of fruit-piercing moth Eudocima phalonia
      (Linnaeus, 1763) (Lepidoptera: Noctuoidea).
AB  - The complete mitochondrial genome of the fruit piercing moth Eudocima phalonia
      (Linnaeus, 1763) (Lepidoptera: Noctuoidea) was sequenced and characterized
      (Genbank Accession No: KY196412). The complete mitogenome is a circular molecule
      of 15,575 bp length, consisting of 13 protein-coding genes (PCGs), two ribosomal
      RNA genes (rrnS and rrnL), 22 transfer RNA (tRNA) genes and an A + T-rich region
      (D-loop). The nucleotide composition of the genome is highly A + T biased,
      accounting for 80.67% of nucleotides. All tRNAs have putative secondary
      structures that are characteristic of mitochondrial tRNA. Most of the PCGs were
      initiated by typical ATN codons. Five genes were initiated by unusual codons.
      Cox1 gene was initiated by an unusual CGA codon and terminated by the typical
      stop codon GAA. Six genes ended with a single T. The A + T-rich region of 336 bp
      consisted of repetitive sequences, including two ATAGA motifs, a 19 bp poly-T
      stretch and three microsatellite-like regions ((TA)4, (TA)6 and two (TA)7).
      Moreover, three large tandem (one 40 bp and two 25 bp) repeated elements were
      identified in A + T-rich region. Phylogenetic analysis using PCGs revealed that
      Superfamily Noctuoidea is a monophyletic group.

PMID- 29021959
TI  - Constrictive pericarditis caused by Cutibacterium (Propionibacterium) acnes: A
      case report and review of literature.
AB  - Constrictive and effusive-constrictive pericarditis are rare cardiac disorders.
      Only rarely are the conditions caused by purulent infection, and even more
      infrequently by anaerobe bacteria. We describe a case of constrictive - and
      effusive-constrictive pericarditis due to Cutibacterium (formerly
      Propionibacterium) acnes in a 75-year old, immunocompetent and previously healthy
      patient without any predisposition. The patient was successfully treated with
      subtotal pericardiectomy and beta-lactam antibacterials. C. acnes was the only
      infectious agent recovered from samples of cultured pericardial tissue. C. acnes
      is a microaerophilic, Gram-positive anaerobic bacillus that is a part of the
      normal flora. In symptomatic patients, however, positive samples should be
      considered as clinically relevant and not dismissed as contamination. Due to the
      low virulence, the capability of adherence and biofilm formation of C. acnes,
      diagnosing C. acnes constrictive pericarditis may be difficult. In the context of
      compatible symptoms, the incubation time of clinical samples should be prolonged
      or supplemented by polymerase chain reaction techniques. Parenteral beta-lactam
      antibacterials are considered the drugs of choice. Severe constrictive and
      effusive-constrictive pericarditis caused by C. acnes is rare, but can be seen
      even in otherwise healthy patients. Prolonged incubation time and polymerase
      chain reaction techniques may be required in order to confirm diagnosis.

PMID- 29021960
TI  - Relapsing EBV encephalitis in a renal transplant recipient.
AB  - In solid organ transplant recipients, Epstein-Barr virus (EBV) can cause active
      central nervous system (CNS) infection or malignant transformation of latently
      infected cells in the CNS, known as post-transplant lymphoproliferative disease
      (PTLD). Reduction of T-cell immunosuppression is the cornerstone of management.
      The role of antivirals with in-vitro activity against herpesviruses in EBV
      related CNS syndromes is controversial, as they have no effect on latent virus.
      We report an unusual case of relapsing EBV encephalitis in a donor-positive, EBV
      negative renal transplant recipient, with response to valganciclovir. Our report
      supports the utility of antiviral treatment for EBV encephalitis, as adjunct to
      reducing immunosuppression, and highlights the need for a systematic approach and
      long-term, multi-disciplinary follow-up of such patients.

PMID- 29021962
TI  - First-year metabolic control guidelines and their impact on future metabolic
      control and neurocognitive functioning in children with PKU.
AB  - : There is a consensus on the importance of early and life-long treatment for PKU
      patients. Still, differences exist on target blood phenylalanine (Phe)
      concentrations for children with PKU in different countries and treatment
      centers. For the first time, long-term metabolic control and child development
      and cognitive functioning is compared between children with mean phenylalanine
      concentrations under 240 MUmol/L (group A), between 240 and 360 MUmol/L (group B)
      or over 360 MUmol/L (group C) during their first year of life. METHODS: 70
      patients diagnosed with PKU through neonatal screening with Phe > 900 MUmol/L,
      were divided into 3 groups: A, B and C, according to mean Phe concentrations and
      standard deviation (SD). Metabolic control during childhood, psychomotor
      development and IQ were compared. RESULTS: In group A, Phe was maintained within
      the recommended range until 6 years of age, in Group B, until 3 years of age, and
      in group C, Phe was always over the recommended range. No significant differences
      were found between the three groups in mental development index (MDI) and motor
      development index (PDI) scores at 12, 24, and 30 months of age, but group C had
      the lowest scores on MDI at all age periods. At preschool and school age, IQ was
      higher in group A compared to group C. CONCLUSION: Results show that mean blood
      Phe concentrations between 120 and 240 MUmol/L during first year of life have a
      positive impact in metabolic control and cognitive functioning during childhood.

PMID- 29021963
TI  - A case of mucosa-associated lymphoid tissue lymphoma of the bladder successfully
      treated with radiotherapy.

PMID- 29021964
TI  - Torsion of ovarian dermoid cyst mimicking obstructing urinary tract stone.

PMID- 29021965
TI  - Simultaneous metachronous renal cell carcinoma and skeletal muscle metastasis
      after radical nephrectomy.

PMID- 29021966
TI  - Testicular hemangioma: A case report.

PMID- 29021961
TI  - Dietary practices in propionic acidemia: A European survey.
AB  - BACKGROUND: The definitive dietary management of propionic acidaemia (PA) is
      unknown although natural protein restriction with adequate energy provision is of
      key importance. AIM: To describe European dietary practices in the management of
      patients with PA prior to the publication of the European PA guidelines. METHODS:
      This was a cross-sectional survey consisting of 27 questions about the dietary
      practices in PA patients circulated to European IMD dietitians and health
      professionals in 2014. RESULTS: Information on protein restricted diets of 186 PA
      patients from 47 centres, representing 14 European countries was collected. Total
      protein intake [PA precursor-free L-amino acid supplements (PFAA) and natural
      protein] met WHO/FAO/UNU (2007) safe protein requirements for age in 36 centres
      (77%). PFAA were used to supplement natural protein intake in 81% (n = 38) of
      centres, providing a median of 44% (14-83%) of total protein requirement. Seventy
      four per cent of patients were prescribed natural protein intakes below
      WHO/FAO/UNU (2007) safe levels in one or more of the following age groups: 0-6 m,
      7-12 m, 1-10 y, 11-16 y and > 16 y. Sixty-three per cent (n = 117) of patients
      were tube fed (74% gastrostomy), but only 22% received nocturnal feeds.
      CONCLUSIONS: There was high use of PFAA with intakes of natural protein commonly
      below WHO/FAO/UNU (2007) safe levels. Optimal dietary management can only be
      determined by longitudinal, multi-centre, prospective case controlled studies.
      The metabolic instability of PA and small patient cohorts in each centre ensure
      that this is a challenging undertaking.

PMID- 29021967
TI  - Small round tumour cells (CD38, CD 79a positive) in the adrenal gland.

PMID- 29021968
TI  - The Unyvero P55 'sample-in, answer-out' pneumonia assay: A performance
      evaluation.
AB  - BACKGROUND: O'Neill's recent Review on Antimicrobial Resistance expressed the
      view that by 2020 high-income countries should make it mandatory to support
      antimicrobial prescribing with rapid diagnostic evidence whenever possible.
      METHODS: Routine microbiology diagnosis of 95 respiratory specimens from patients
      with severe infection were compared with those generated by the Unyvero P55 test,
      which detects 20 pathogens and 19 antimicrobial resistance markers. Supplementary
      molecular testing for antimicrobial resistance genes, comprehensive culture
      methodology and 16S rRNA sequencing were performed. RESULTS: Unyvero P55 produced
      85 valid results, 67% of which were concordant with those from the routine
      laboratory. Unyvero P55 identified more potential pathogens per specimen than
      routine culture (1.34 vs. 0.47 per specimen). Independent verification using 16S
      rRNA sequencing and culture (n = 10) corroborated 58% of additional detections
      compared to routine microbiology. Overall the average sensitivity for organism
      detection by Unyvero P55 was 88.8% and specificity was 94.9%. While Unyvero P55
      detected more antimicrobial resistance markers than routine culture, some
      instances of phenotypic resistance were missed. CONCLUSIONS: The Unyvero P55 is a
      rapid pathogen detection test for lower respiratory specimens, which identifies a
      larger number of pathogens than routine microbiology. The clinical significance
      of these additional organisms is yet to be determined. Further studies are
      required to determine the effect of the test in practise on antimicrobial
      prescribing and patient outcomes.

PMID- 29021969
TI  - *K-means and cluster models for cancer signatures.
AB  - We present *K-means clustering algorithm and source code by expanding statistical
      clustering methods applied in https://ssrn.com/abstract=2802753 to quantitative
      finance. *K-means is statistically deterministic without specifying initial
      centers, etc. We apply *K-means to extracting cancer signatures from genome data
      without using nonnegative matrix factorization (NMF). *K-means' computational
      cost is a fraction of NMF's. Using 1389 published samples for 14 cancer types, we
      find that 3 cancers (liver cancer, lung cancer and renal cell carcinoma) stand
      out and do not have cluster-like structures. Two clusters have especially high
      within-cluster correlations with 11 other cancers indicating common underlying
      structures. Our approach opens a novel avenue for studying such structures. *K
      means is universal and can be applied in other fields. We discuss some potential
      applications in quantitative finance.

PMID- 29021970
TI  - Quantification of mitochondrial DNA copy number in suspected cancer patients by a
      well optimized ddPCR method.
AB  - Changes in mitochondrial DNA (mtDNA) content is a useful clinical biomarker for
      various diseases, however results are controversial as several analytical factors
      can affect measurement of mtDNA. MtDNA is often quantified by taking ratio
      between a target mitochondrial gene and a reference nuclear gene (mtDNA/nDNA)
      using quantitative real time PCR often on two separate experiments. It measures
      relative levels by using external calibrator which may not be comparable across
      laboratories. We have developed and optimized a droplet digital PCR (ddPCR) based
      method for quantification of absolute copy number of both mtDNA and nDNA gene in
      whole blood. Finally, the role of mtDNA in suspected cancer patients referred to
      a cancer diagnostic center was investigated. Analytical factors which can result
      in false quantification of mtDNA have been optimized and both target and
      reference have been quantified simultaneously with intra- and inter-assay
      coefficient variances as 3.1% and 4.2% respectively. Quantification of mtDNA show
      that compared to controls, solid tumors (but not hematologic malignancies) and
      other diseases had significantly lower copy number of mtDNA. Higher mtDNA
      (highest quartile) was associated with a significantly lower risk of both solid
      tumors and other diseases, independent of age and sex. Receiver operating curve
      demonstrated that mtDNA levels could differentiate controls from patients with
      solid tumors and other diseases. Quantification of mtDNA by a well optimized
      ddPCR method showed that its depletion may be a hallmark of general illness and
      can be used to stratify healthy individuals from patients diagnosed with cancer
      and other chronic diseases.

PMID- 29021971
TI  - Evaluation of relative quantification of alternatively spliced transcripts using
      droplet digital PCR.
AB  - INTRODUCTION: For the relative quantification of isoform expression, RT-qPCR has
      been the gold standard for over a decade. More recently, digital PCR is becoming
      widely implemented, as it is promised to be more accurate, sensitive and less
      affected by inhibitors, without the need for standard curves. In this study we
      evaluated RT-qPCR versus RT-droplet digital PCR (ddPCR) for the relative
      quantification of isoforms in controls and carriers of the splice site mutation
      BRCA1 c.212+3A>G, associated with increased expression of several isoforms.
      MATERIALS AND METHODS: RNA was extracted from EBV cell lines of controls and
      heterozygous BRCA1 c.212+3A>G carriers. Transcript-specific plasmids were
      available to determine the efficiency, precision, reproducibility and accuracy of
      each method. RESULTS: Both ddPCR and RT-qPCR were able to accurately quantify all
      targets and showed the same LOB, LOD and LOQ; also precision and reproducibility
      were similar. Both techniques have the same dynamic range and linearity at
      biologically relevant template concentrations. However, a significantly higher
      cost and workload was required for ddPCR experiments. CONCLUSIONS: Our study
      recognizes the potential and validity of digital PCR but shows the value of a
      highly optimized qPCR for the relative quantification of isoforms. Cost
      efficiency and simplicity turned out to be better for RT-qPCR.

PMID- 29021972
TI  - Evaluating Factors for Prophylactic Feeding Tube Placement in Gastroesophageal
      Cancer Patients Undergoing Chemoradiotherapy.
AB  - PURPOSE: Though better studied in head/neck cancers, there are currently no
      studies on timing of feeding tube (FT) placement in patients with
      gastroesophageal cancer. This study sought to discern characteristics of patients
      who used versus did not use a prophylactic FT (pFT), and also analyzed factors
      associated with placement of FTs during chemoradiotherapy (CRT).
      METHODS/MATERIALS: From 1998 to 2013, 1,329 patients underwent neoadjuvant CRT,
      of which 323 received an FT. Patients for whom FTs were placed prior to treatment
      due to tumor occlusion or substantial weight loss (n = 130), and those with FTs
      placed following treatment (n = 43) were excluded. One hundred patients had pFTs
      placed, and 50 underwent placement during CRT. The following was collected for
      each patient: demographic/patient information, oncologic/treatment
      characteristics, and CRT tolerance. RESULTS: No significant differences were
      found in any parameter between cohorts that used (n = 66) versus did not use a
      pFT (n = 34); on univariate and multivariate analyses, no pretreatment
      characteristic associated with using a pFT. When compared with patients who used
      a pFT (n = 66), those who required an FT during CRT (n = 50) had lower body mass
      index (p = 0.045), underwent higher-dose radiotherapy (p = 0.003), and received
      induction chemotherapy (p = 0.031). On multivariate analysis, receipt of
      induction chemotherapy and greater weight loss and esophagitis during treatment
      were associated with placement of FTs during CRT (p < 0.05). CONCLUSION: Of our
      cohort who received pFTs, there were no clinical factors that predicted for their
      use. Patients must be closely monitored for weight loss and esophagitis when
      receiving CRT in order to intervene prior to further worsening of toxicities.

PMID- 29021974
TI  - Role of Low-Molecular-Mass Penicillin-Binding Proteins, NagZ and AmpR in AmpC
      beta-lactamase Regulation of Yersinia enterocolitica.
AB  - Yersinia enterocolitica encodes a chromosomal AmpC beta-lactamase under the
      regulation of the classical ampR-ampC system. To obtain a further understanding
      to the role of low-molecular-mass penicillin-binding proteins (LMM PBPs)
      including PBP4, PBP5, PBP6, and PBP7, as well as NagZ and AmpR in ampC regulation
      of Y. enterocolitica, series of single/multiple mutant strains were
      systematically constructed and the ampC expression levels were determined by
      luxCDABE reporter system, reverse transcription-PCR (RT-PCR) and beta-lactamase
      activity test. Sequential deletion of PBP5 and other LMM PBPs result in a
      continuously growing of ampC expression level, the beta-lactamse activity of
      quadruple deletion strain YEDelta4Delta5Delta6Delta7 (pbp4, pbp5, pbp6, and pbp7
      inactivated) is approached to the YEDeltaD123 (ampD1, ampD2, and ampD3
      inactivated). Deletion of nagZ gene caused two completely different results in
      YEDeltaD123 and YEDelta4Delta5Delta6Delta7, NagZ is indispensable for
      YEDelta4Delta5Delta6Delta7 ampC derepression phenotype but dispensable for
      YEDeltaD123. AmpR is essential for ampC hyperproduction in these two types of
      strains, inactivation of AmpR notable reduced the ampC expression level in both
      YEDeltaD123 and YEDelta4Delta5Delta6Delta7.

PMID- 29021976
TI  - Learning Curves for Laparoscopic Repair of Inguinal Hernia and Communicating
      Hydrocele in Children.
AB  - INTRODUCTION: We analyzed the department and surgeon learning curves during
      implementation of the percutaneous internal ring suturing (PIRS) technique in our
      department. METHODS: Children proposed for inguinal hernia or communicating
      hydrocele repair were included (n = 607). After mentorship, all surgeons were
      free to propose open or PIRS repair. From gathered data, we assessed department
      and surgeon learning curves through cumulative experience focusing in
      perioperative complications, conversion, ipsilateral recurrence, postoperative
      complications, and metachronous hernia, with benchmarks defined by open repair.
      RESULTS: Department-centered analysis revealed that perioperative complications,
      conversion, and ipsilateral recurrence rates were higher in the beginning,
      reaching the benchmarks when each surgeon performed, at least, 35 laparoscopic
      repairs. Postoperative complications and metachronous hernia rates were
      independent from learning curves, with the metachronous hernia rate being
      significantly lower in PIRS patients. During the program, the percentage of males
      in those operated by PIRS progressively increased reaching the percentage of
      males, in our sample, when department operated over 230 cases. CONCLUSION: Thirty
      five laparoscopic cases per surgeon are required for perioperative complications,
      conversion, and ipsilateral recurrence reach the benchmark. The gap between the
      percentage of males, in those operated by PIRS and in those proposed for surgery,
      monitors the confidence of the team in the program.

PMID- 29021973
TI  - Brucella Rough Mutant Induce Macrophage Death via Activating IRE1alpha Pathway of
      Endoplasmic Reticulum Stress by Enhanced T4SS Secretion.
AB  - Brucella is a Gram-negative facultative intracellular pathogen that causes the
      worldwide zoonosis, known as brucellosis. Brucella virulence relies mostly on its
      ability to invade and replicate within phagocytic cells. The type IV secretion
      system (T4SS) and lipopolysaccharide are two major Brucella virulence factors.
      Brucella rough mutants reportedly induce the death of infected macrophages, which
      is T4SS dependent. However, the underlying molecular mechanism remains unclear.
      In this study, the T4SS secretion capacities of Brucella rough mutant and its
      smooth wild-type strain were comparatively investigated, by constructing the
      firefly luciferase fused T4SS effector, BPE123 and VceC. In addition,
      quantitative real-time PCR and western blotting were used to analyze the T4SS
      expression. The results showed that T4SS expression and secretion were enhanced
      significantly in the Brucella rough mutant. We also found that the activity of
      the T4SS virB operon promoter was notably increased in the Brucella rough mutant,
      which depends on quorum sensing-related regulators of VjbR upregulation. Cell
      infection and cell death assays revealed that deletion of vjbR in the Brucella
      rough mutant absolutely abolished cytotoxicity within macrophages by
      downregulating T4SS expression. This suggests that up-regulation of T4SS promoted
      by VjbR in rough mutant DeltarfbE contribute to macrophage death. In addition, we
      found that the Brucella rough mutant induce macrophage death via activating
      IRE1alpha pathway of endoplasmic reticulum stress. Taken together, our study
      provide evidence that in comparison to the Brucella smooth wild-type strain, VjbR
      upregulation in the Brucella rough mutant increases transcription of the virB
      operon, resulting in overexpression of the T4SS gene, accompanied by the over
      secretion of effecter proteins, thereby causing the death of infected macrophages
      via activating IRE1alpha pathway of endoplasmic reticulum stress, suggesting
      novel insights into the molecular mechanisms associated with Brucella rough
      mutant-induced macrophage cytotoxicity.

PMID- 29021975
TI  - Effect of melatonin versus vitamin D as antioxidant and Hepatoprotective agents
      in STZ-induced diabetic rats.
AB  - BACKGROUND: Diabetes mellitus (DM) is a serious chronic disease, with multiple
      complications including hepatopathy associated with imbalance of the oxidative
      status. The purpose of this study is to observe possible protective effects of
      vitamin-D and melatonin on glucose profile, antioxidant-oxidant status, lipid
      peroxidation, and histopathological protection of the liver in streptozotocin
      induced diabetic rats. METHODS: Eighty three male albino rats were divided into
      nine groups as follows: G1 (n = 10) Normal control rats; G2 (n = 8) were normal
      rats treated with melatonin only; G3 (n = 10) were normal rats treated with
      vitamin D only; G4 (n = 9) were diabetic rats, which received no medications; G5
      (n = 8) were diabetic rat treated with insulin only; G6 (n = 10) were diabetic
      rats treated with melatonin only; G7 (n = 9) were diabetic rats treated with
      melatonin and insulin; G8 (n = 9) were diabetic rats treated with vitamin D only;
      G9 (n = 10) were diabetic rats treated with vitamin D and insulin. Two months
      post treatment, blood was collected to measure: Fasting blood sugar (FBS),
      glycosylated hemoglobin (HbA1c), fructosamine (FA), total antioxidant capacity
      (TAC), malondialdahyde (MDA). livers were isolated for histopathological study.
      RESULTS: As compared to normal rats, our results demonstrate that glucose,
      fructosamine and HbA1c levels is increased in diabetic groups and declined to
      lesser levels in treated groups. TAC level of diabetic rats is not significantly
      changed. Vitamin D administration significantly increased TAC while it is not
      changed with melatonin either in treated or non-treated groups. The liver of
      diabetic rats shows only mild focal microvesicular fatty degeneration. The liver
      of diabetic rats treated with insulin shows degeneration of cell edema in the
      stroma. The liver of diabetic rats treated with melatonin with or without
      insulin, exhibited marked improvement. The liver of diabetic rats treated with
      vitamin D with or without insulin, shows degeneration of cells and edema in the
      stroma. CONCLUSION: Our results demonstrated the beneficial antioxidant effect of
      vitamin D administration to normal and diabetic rats as compared to melatonin.
      Nevertheless, melatonin still shows more therapeutic effect on liver cell injury
      induced by induction of diabetes.

PMID- 29021978
TI  - Global Health Teaching in India: A Curricular Landscape.
AB  - Today, health has transcended national boundaries and become more multifaceted.
      Global health has evolved as a new paradigm and is recently being identified as a
      thrust area now in India. Despite an existing need for a standardized global
      health curriculum, there is little information available on its education and
      curriculum in medical and health education space. In the Indian context, we are
      yet to have a fuller picture of the current status, including, content,
      structure, selection, teaching methods of global health, and how students are
      evaluated in India. The objective of this study was to map courses relating to
      studies on global health in India and analyze its mode of delivery. A detailed
      Internet search was carried out to identify global health courses and analyzed
      for: (i) whether global health is a part of the teaching curriculum, (ii) mode of
      teaching, (iii) broad contents, (iv) instructional formats, (v) assessment, and
      (vi) selection process. It was found that delivery of global health education in
      India was fragmented with limited focus at the undergraduate and postgraduate
      levels. Global health teaching was largely based on certificate courses or online
      courses, with hardly any institutions imparting a distinct global health
      education program. There is also no definite specification as to which institutes
      can impart teaching on global health education and what the specific eligibility
      requirements are. Our analysis suggests that efforts should be directed toward
      integrating global health education into broader public health curriculum. At the
      same time, the need for generation of global health leaders, creation of a common
      forum for addressing merits and demerits of global health issues, as well as
      creation of more opportunities for placements are recognized.

PMID- 29021981
TI  - Commentary: CRISPR-Cas Encoding of a Digital Movie into the Genomes of a
      Population of Living Bacteria.

PMID- 29021980
TI  - Hydrogen Sulfide: A Worthwhile Tool in the Design of New Multitarget Drugs.
AB  - H2S is a gaseous molecule able to trigger a plethora of central physiological and
      pharmacological effects as antioxidant, pro- and anti-inflammatory, pro- and anti
      nociceptive, neuromodulator, and cytoprotective. The polypharmacology of H2S
      depends on the wide variety of targets implicated, but, despite the efforts, the
      mechanisms of action that should clarify its activity are still not completely
      unrevealed. Nevertheless, many attempts to exploit the multifaceted profile of
      this molecule have already been accomplished and many chemical entities
      containing an H2S-releasing pharmacophore have been synthetized. Here we discuss
      recent investigations on multitarget molecules able to release H2S, with a
      particular focus on the combinations of "native drug" with moieties structurally
      able to release H2S and their applications as therapeutic tools in bone disease,
      gastrointestinal system and neurodegenerative disorders.

PMID- 29021979
TI  - Everybody Brush! Consumer Satisfaction with a Tooth Decay Prevention Program.
AB  - INTRODUCTION: Twice-daily caregiver-supervised toothbrushing with fluoridated
      toothpaste is an effective and widely recommended strategy to prevent tooth decay
      in children. Qualitative research suggests that low-income caregivers know the
      recommendation but would benefit from toothbrushing supplies and advice about how
      to introduce this health behavior especially as the child becomes older and
      asserts autonomy to do it "myself." Our objective is to assess consumer
      satisfaction with the evidence-based theory-informed campaign and usefulness of
      materials that were home delivered. The focus of the evaluation was families with
      children <36 months of age because of the high incidence of disease in this
      population. METHODS: A dental care organization designed and implemented
      Everybody Brush! in three counties of Central Oregon. Participants were families
      of Medicaid-insured children <21 years of age. Participants were randomly
      assigned to one of the three study groups: test (supplies, voice/printed
      messages, telephone support), active (supplies), and a waitlist control. Program
      materials were in English and Spanish. Caregivers of children <36 months were
      interviewed at the beginning and end of the program. RESULTS: A total of 83,148
      toothbrushing kits were mailed to 21,743 families. In addition, 93,766 printed
      messages and 110,367 recorded messages were sent to half of the families.
      Caregivers were highly satisfied. On a global rating scale from 0 to 10 (worst to
      best program possible), they rated the program 9.5 on average (median: 10, SD
      0.9). On a scale from 0 to 10 (not at all to very useful), mean ratings for
      usefulness of the toothbrushing supplies was 9.5 (SD = 1.5), for the printed
      postcard messages was 7.2 (SD 3.6), and for the voice telephone messages was 6.5
      (SD 3.9). DISCUSSION: A dental care organization carried out a complex community
      intervention designed to address excess tooth decay among low-income children.
      Caregivers were highly satisfied with the Everybody Brush! program and
      toothbrushing supplies were considered the most useful, followed by printed
      messages. Voice telephone messages were rated least useful. Further evaluation of
      the impact of the program on toothbrushing behavior and dental-care utilization
      is underway.

PMID- 29021977
TI  - The Consensus from the Mycobacterium avium ssp. paratuberculosis (MAP) Conference
      2017.
AB  - On March 24 and 25, 2017 researchers and clinicians from around the world met at
      Temple University in Philadelphia to discuss the current knowledge of
      Mycobacterium avium ssp. paratuberculosis (MAP) and its relationship to human
      disease. The conference was held because of shared concern that MAP is a zoonotic
      bacterium that poses a threat not only to animal health but also human health. In
      order to further study this problem, the conferees discussed ways to improve MAP
      diagnostic tests and discussed potential future anti-MAP clinical trials. The
      conference proceedings may be viewed on the www.Humanpara.org website. A summary
      of the salient work in this field is followed by recommendations from a majority
      of the conferees.

PMID- 29021982
TI  - Autologous Periosteum-Derived Micrografts and PLGA/HA Enhance the Bone Formation
      in Sinus Lift Augmentation.
AB  - Sinus lift augmentation is a procedure required for the placement of a dental
      implant, whose success can be limited by the quantity or quality of available
      bone. To this purpose, the first aim of the current study was to evaluate the
      ability of autologous periosteum-derived micrografts and Poly(lactic-co-glycolic
      acid) (PLGA) supplemented with hydroxyl apatite (HA) to induce bone augmentation
      in the sinus lift procedure. Secondly, we compared the micrograft's behavior with
      respect to biomaterial alone, including Bio-Oss(r) and PLGA/HA, commercially
      named Alos. Sinus lift procedure was performed on 24 patients who required dental
      implants and who, according to the study design and procedure performed, were
      divided into three groups: group A (Alos + periosteum-derived micrografts); group
      B (Alos alone); and group C (Bio-Oss(r) alone). Briefly, in group A, a small
      piece of periosteum was collected from each patient and mechanically
      disaggregated by Rigenera(r) protocol using the Rigeneracons medical device. This
      protocol allowed for the obtainment of autologous micrografts, which in turn were
      used to soak the Alos scaffold. At 6 months after the sinus lift procedure and
      before the installation of dental implants, histological and radiographic
      evaluations in all three groups were performed. In group A, where sinus lift
      augmentation was performed using periosteum-derived micrografts and Alos, the
      bone regeneration was much faster than in the control groups where it was
      performed with Alos or Bio-Oss(r) alone (groups B and C, respectively). In
      addition, the radiographic evaluation in the patients of group A showed a radio
      opacity after 4 months, while after 6 months, the prosthetic rehabilitation was
      improved and was maintained after 2 years post-surgery. In summary, we report on
      the efficacy of periosteum-derived micrografts and Alos to augment sinus lift in
      patients requiring dental implants. This efficacy is supported by an increased
      percentage of vital mineralized tisssue in the group treated with both periosteum
      derived micrografts and Alos, with respect to the control group of Alos or Bio
      Oss(r) alone, as confirmed by histological analysis and radiographic evaluations
      at 6 months from treatment.

PMID- 29021983
TI  - An Integrated Framework for Process-Driven Model Construction in Disease Ecology
      and Animal Health.
AB  - Process models that focus on explicitly representing biological mechanisms are
      increasingly important in disease ecology and animal health research. However,
      the large number of process modelling approaches makes it difficult to decide
      which is most appropriate for a given disease system and research question. Here,
      we discuss different motivations for using process models and present an
      integrated conceptual analysis that can be used to guide the construction of
      infectious disease process models and comparisons between them. Our presentation
      complements existing work by clarifying the major differences between modelling
      approaches and their relationship with the biological characteristics of the
      epidemiological system. We first discuss distinct motivations for using process
      models in epidemiological research, identifying the key steps in model design and
      use associated with each. We then present a conceptual framework for guiding
      model construction and comparison, organised according to key aspects of
      epidemiological systems. Specifically, we discuss the number and type of disease
      states, whether to focus on individual hosts (e.g., cows) or groups of hosts
      (e.g., herds or farms), how space or host connectivity affect disease
      transmission, whether demographic and epidemiological processes are periodic or
      can occur at any time, and the extent to which stochasticity is important. We use
      foot-and-mouth disease and bovine tuberculosis in cattle to illustrate our
      discussion and support explanations of cases in which different models are used
      to address similar problems. The framework should help those constructing models
      to structure their approach to modelling decisions and facilitate comparisons
      between models in the literature.

PMID- 29021984
TI  - MRI Findings of Early-Stage Hyperacute Hemorrhage Causing Extramedullary
      Compression of the Cervical Spinal Cord in a Dog with Suspected Steroid
      Responsive Meningitis-Arteritis.
AB  - A 9-month-old female Weimaraner was presented to the emergency service due to
      episodes of fever and neck pain. Physical examination revealed a stiff neck
      posture and elevated body temperature. Shortly after clinical examination was
      performed, the dog developed peracute onset of non-ambulatory tetraparesis
      compatible with a C1-C5 spinal cord (SC) lesion. Immediately thereafter (<1 h),
      MRI of the cervical SC was performed with a 3-T scanner. A left ventrolateral
      intradural-extramedullary SC compression caused by a round-shaped structure at
      the level of C3--C4 was evidenced. The structure was iso- to slightly
      hyperintense in T1-weighted (T1W) sequences compared to SC parenchyma and
      hyperintense in T2-weighted, gradient echo, and fluid-attenuated inversion
      recovery. Moreover, the structure showed a strong homogeneous contrast uptake in
      T1W sequences. Cerebrospinal fluid (CSF) analysis revealed a mixed pleocytosis,
      as well as elevated protein and erythrocyte count. Early-stage hyperacute
      extramedullary hemorrhage was suspected due to immune mediated vasculitis. The
      dog was maintained under general anesthesia and artificial ventilation for 24 h
      and long-term therapy with corticosteroids and physiotherapy was initiated. Eight
      weeks after initial presentation, the dog was ambulatory, slightly tetraparetic.
      Follow-up MRI showed a regression of the round-shaped structure and pleocytosis
      was not evident in CSF analysis. This report describes an early-stage hyperacute
      extramedullary hemorrhage, a condition rarely recorded in dogs even in
      experimental settings.

PMID- 29021985
TI  - Turbo-Satori: a neurofeedback and brain-computer interface toolbox for real-time
      functional near-infrared spectroscopy.
AB  - Turbo-Satori is a neurofeedback and brain-computer interface (BCI) toolbox for
      real-time functional near-infrared spectroscopy (fNIRS). It incorporates multiple
      pipelines from real-time preprocessing and analysis to neurofeedback and BCI
      applications. The toolbox is designed with a focus in usability, enabling a fast
      setup and execution of real-time experiments. Turbo-Satori uses an incremental
      recursive least-squares procedure for real-time general linear model calculation
      and support vector machine classifiers for advanced BCI applications. It
      communicates directly with common NIRx fNIRS hardware and was tested extensively
      ensuring that the calculations can be performed in real time without a
      significant change in calculation times for all sampling intervals during ongoing
      experiments of up to 6 h of recording. Enabling immediate access to advanced
      processing features also allows the use of this toolbox for students and
      nonexperts in the field of fNIRS data acquisition and processing. Flexible
      network interfaces allow third party stimulus applications to access the
      processed data and calculated statistics in real time so that this information
      can be easily incorporated in neurofeedback or BCI presentations.

PMID- 29021988
TI  - Special Section Guest Editorial: Visions of Safety: Perspectives on Radiation
      Exposure and Risk in Medical Imaging.
AB  - This guest editorial introduces the special section on Visions of Safety:
      Perspectives on Radiation Exposure and Risk in Medical Imaging.

PMID- 29021987
TI  - Spatial variation in the hemoglobin phase of oxygenation and deoxygenation in the
      developing cortex of infants.
AB  - Spontaneous low-frequency oscillatory changes in oxygenated hemoglobin (oxy-Hb)
      and deoxygenated hemoglobin (deoxy-Hb) are observed using functional near
      infrared spectroscopy (fNIRS). A previous study showed that the time-averaged
      phase difference between oxy-Hb and deoxy-Hb changes, referred to as hemoglobin
      phase of oxygenation and deoxygenation (hPod), is sensitive to the development of
      the cortex. We examined phase-locking index of hPod, referred to as [Formula: see
      text], in addition to hPod, in neonates and 3- and 6-month-old infants using the
      94-channel fNIRS data, which covered large lateral regions of the cortex. The
      results showed that (1) developmental changes in hPod exhibited spatial
      dependency; (2) [Formula: see text] increased between the neonate group and 3
      month-old infant group over the posterior, but not anterior, regions of the
      cortex; and (3) the cortical regions of each age group were clustered in several
      domains with specific characteristics of hPod and [Formula: see text]. This study
      indicates that the neonatal cortex is composed of regions with specific
      characteristics of hPod and [Formula: see text], and drastic changes occur
      between the neonatal period and 3 months of age. This study suggests that hPod
      and [Formula: see text] are sensitive to the cortical region-specific development
      of the circulatory, blood flow, metabolic, and neurovascular functions in young
      infants.

PMID- 29021986
TI  - Integrated treatment modality of cathodal-transcranial direct current stimulation
      with peripheral sensory stimulation affords neuroprotection in a rat stroke
      model.
AB  - Cathodal-transcranial direct current stimulation induces therapeutic effects in
      animal ischemia models by preventing the expansion of ischemic injury during the
      hyperacute phase of ischemia. However, its efficacy is limited by an accompanying
      decrease in cerebral blood flow. On the other hand, peripheral sensory
      stimulation can increase blood flow to specific brain areas resulting in rescue
      of neurovascular functions from ischemic damage. Therefore, the two modalities
      appear to complement each other to form an integrated treatment modality. Our
      results showed that hemodynamics was improved in a photothrombotic ischemia
      model, as cerebral blood volume and hemoglobin oxygen saturation ([Formula: see
      text]) recovered to 71% and 76% of the baseline values, respectively.
      Furthermore, neural activities, including somatosensory-evoked potentials (110%
      increase), the alpha-to-delta ratio (27% increase), and the [Formula: see text]
      ratio (27% decrease), were also restored. Infarct volume was reduced by 50% with
      a 2-fold preservation in the number of neurons and a 6-fold reduction in the
      number of active microglia in the infarct region compared with the untreated
      group. Grip strength was also better preserved (28% higher) compared with the
      untreated group. Overall, this nonpharmacological, nonintrusive approach could be
      prospectively developed into a clinical treatment modality.

PMID- 29021989
TI  - Patient dose monitoring and the use of diagnostic reference levels for the
      optimization of protection in medical imaging: current status and challenges
      worldwide.
AB  - Optimization is one of the key concepts of radiation protection in medical
      imaging. In practice, it involves compromising between the image quality and dose
      to the patient; the dose should not be higher than necessary to achieve an image
      quality (or diagnostic information) needed for the clinical task. Monitoring
      patient dose is a key requirement toward optimization. The concept of diagnostic
      reference level (DRL) was introduced by the International Commission on
      Radiological Protection as a practical tool for optimization. Unfortunately, this
      concept has not been applied consistently worldwide. To review the current
      strengths and weaknesses worldwide and to promote improvements, the International
      Atomic Energy Agency organized a Technical Meeting on patient dose monitoring and
      the use of DRLs on May 2016. This paper reports a summary of the findings and
      conclusions from the meeting. The strengths and weaknesses were generally
      different in less-developed countries compared with developed countries. Possible
      improvements were suggested in six areas: human resources and responsibilities,
      training, safety and quality culture, regulations, funding, and tools and
      methods. An overall conclusion was that radiation protection requires a patient
      centric approach and a transfer from purely reactive to increasingly proactive
      optimization, whereby the best outcome is expected from good teamwork.

PMID- 29021990
TI  - Discovery radiomics via evolutionary deep radiomic sequencer discovery for
      pathologically proven lung cancer detection.
AB  - While lung cancer is the second most diagnosed form of cancer in men and women, a
      sufficiently early diagnosis can be pivotal in patient survival rates. Imaging
      based, or radiomics-driven, detection methods have been developed to aid
      diagnosticians, but largely rely on hand-crafted features that may not fully
      encapsulate the differences between cancerous and healthy tissue. Recently, the
      concept of discovery radiomics was introduced, where custom abstract features are
      discovered from readily available imaging data. We propose an evolutionary deep
      radiomic sequencer discovery approach based on evolutionary deep intelligence.
      Motivated by patient privacy concerns and the idea of operational artificial
      intelligence, the evolutionary deep radiomic sequencer discovery approach
      organically evolves increasingly more efficient deep radiomic sequencers that
      produce significantly more compact yet similarly descriptive radiomic sequences
      over multiple generations. As a result, this framework improves operational
      efficiency and enables diagnosis to be run locally at the radiologist's computer
      while maintaining detection accuracy. We evaluated the evolved deep radiomic
      sequencer (EDRS) discovered via the proposed evolutionary deep radiomic sequencer
      discovery framework against state-of-the-art radiomics-driven and discovery
      radiomics methods using clinical lung CT data with pathologically proven
      diagnostic data from the LIDC-IDRI dataset. The EDRS shows improved sensitivity
      (93.42%), specificity (82.39%), and diagnostic accuracy (88.78%) relative to
      previous radiomics approaches.

PMID- 29021991
TI  - Segmentation of multicolor fluorescence in situ hybridization images using an
      improved fuzzy C-means clustering algorithm by incorporating both spatial and
      spectral information.
AB  - Multicolor fluorescence in situ hybridization (M-FISH) is a multichannel imaging
      technique for rapid detection of chromosomal abnormalities. It is a critical and
      challenging step to segment chromosomes from M-FISH images toward better
      chromosome classification. Recently, several fuzzy C-means (FCM) clustering-based
      methods have been proposed for M-FISH image segmentation or classification, e.g.,
      adaptive fuzzy C-means (AFCM) and improved AFCM (IAFCM), but most of these
      methods used only one channel imaging information with limited accuracy. To
      improve the segmentation for better accuracy and more robustness, we proposed an
      FCM clustering-based method, denoted by spatial- and spectral-FCM. Our method has
      the following advantages: (1) it is able to exploit information from neighboring
      pixels (spatial information) to reduce the noise and (2) it can incorporate pixel
      information across different channels simultaneously (spectral information) into
      the model. We evaluated the performance of our method by comparing with other FCM
      based methods in terms of both accuracy and false-positive detection rate on
      synthetic, hybrid, and real images. The comparisons on 36 M-FISH images have
      shown that our proposed method results in higher segmentation accuracy ([Formula:
      see text]) and a lower false-positive ratio ([Formula: see text]) than
      conventional FCM (accuracy: [Formula: see text], and false-positive ratio:
      [Formula: see text]) and the IAFCM (accuracy: [Formula: see text] and false
      positive ratio: [Formula: see text]) methods by incorporating both spatial and
      spectral information from M-FISH images.

PMID- 29021992
TI  - Classifying symmetrical differences and temporal change for the detection of
      malignant masses in mammography using deep neural networks.
AB  - We investigate the addition of symmetry and temporal context information to a
      deep convolutional neural network (CNN) with the purpose of detecting malignant
      soft tissue lesions in mammography. We employ a simple linear mapping that takes
      the location of a mass candidate and maps it to either the contralateral or prior
      mammogram, and regions of interest (ROIs) are extracted around each location. Two
      different architectures are subsequently explored: (1) a fusion model employing
      two datastreams where both ROIs are fed to the network during training and
      testing and (2) a stagewise approach where a single ROI CNN is trained on the
      primary image and subsequently used as a feature extractor for both primary and
      contralateral or prior ROIs. A "shallow" gradient boosted tree classifier is then
      trained on the concatenation of these features and used to classify the joint
      representation. The baseline yielded an AUC of 0.87 with confidence interval
      [0.853, 0.893]. For the analysis of symmetrical differences, the first
      architecture where both primary and contralateral patches are presented during
      training obtained an AUC of 0.895 with confidence interval [0.877, 0.913], and
      the second architecture where a new classifier is retrained on the concatenation
      an AUC of 0.88 with confidence interval [0.859, 0.9]. We found a significant
      difference between the first architecture and the baseline at high specificity
      with [Formula: see text]. When using the same architectures to analyze temporal
      change, we yielded an AUC of 0.884 with confidence interval [0.865, 0.902] for
      the first architecture and an AUC of 0.879 with confidence interval [0.858,
      0.898] in the second setting. Although improvements for temporal analysis were
      consistent, they were not found to be significant. The results show our proposed
      method is promising and we suspect performance can greatly be improved when more
      temporal data become available.

PMID- 29021994
TI  - Stereotaxic Adeno-associated Virus Injection and Cannula Implantation in the
      Dorsal Raphe Nucleus of Mice.
AB  - Optogenetic methods are now widespread in neuroscience research. Here we present
      a detailed surgical procedure to inject adeno-associated viruses and implant
      optic fiber cannulas in the dorsal raphe nucleus (DRN) of living mice. Combined
      with transgenic mouse lines, this protocol allows specific targeting of serotonin
      producing neurons in the brain. It includes fixing a mouse in a stereotaxic
      frame, performing a craniotomy, virus injection and fiber implantation. Animals
      can be later used in behavioral experiments, combined with optogenetic
      manipulations (Dugue et al., 2014; Correia et al., 2017) or monitoring of
      neuronal activity (Matias et al., 2017). The described procedure is a fundamental
      step in both optogenetic and fiber photometry experiments of deep brain areas. It
      is optimized for serotonin neurons in the DRN, but it can be applied to any other
      cell type and brain region. When using transgenic mouse lines that express
      functionally relevant levels of optogenetic tools or reporter lines, the virus
      injection step can be skipped and the protocol is reduced to the cannula
      implantation procedure.

PMID- 29021993
TI  - Multisite concordance of apparent diffusion coefficient measurements across the
      NCI Quantitative Imaging Network.
AB  - Diffusion weighted MRI has become ubiquitous in many areas of medicine, including
      cancer diagnosis and treatment response monitoring. Reproducibility of diffusion
      metrics is essential for their acceptance as quantitative biomarkers in these
      areas. We examined the variability in the apparent diffusion coefficient (ADC)
      obtained from both postprocessing software implementations utilized by the NCI
      Quantitative Imaging Network and online scan time-generated ADC maps. Phantom and
      in vivo breast studies were evaluated for two ([Formula: see text]) and four
      ([Formula: see text]) [Formula: see text]-value diffusion metrics. Concordance of
      the majority of implementations was excellent for both phantom ADC measures and
      in vivo [Formula: see text], with relative biases [Formula: see text] ([Formula:
      see text]) and [Formula: see text] (phantom [Formula: see text]) but with higher
      deviations in ADC at the lowest phantom ADC values. In vivo [Formula: see text]
      concordance was good, with typical biases of [Formula: see text] to 3% but higher
      for online maps. Multiple b-value ADC implementations were separated into two
      groups determined by the fitting algorithm. Intergroup mean ADC differences
      ranged from negligible for phantom data to 2.8% for [Formula: see text] in vivo
      data. Some higher deviations were found for individual implementations and online
      parametric maps. Despite generally good concordance, implementation biases in ADC
      measures are sometimes significant and may be large enough to be of concern in
      multisite studies.

PMID- 29021996
TI  - Characterisation of mineral deposition systems associated with rock art in the
      Kimberley region of northwest Australia.
AB  - This data article contains mineralogical and chemical data from mineral
      accretions sampled from rock art shelters in the Kimberley region of north west
      Australia. The accretions were collected both on and off pigment and engraved
      rock art of varying styles observed in the Kimberley with an aim of providing a
      thorough understanding of the formation and preservation of such materials in the
      context of dating [1]. This contribution includes processed powder X-ray
      Diffraction data, Scanning Electron Microscopy energy dispersive spectroscopy
      data, and Laser Ablation ICP-MS trace element mapping data.

PMID- 29021995
TI  - Tumor-induced osteomalacia.
AB  - Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome clinically
      characterized by bone pain, fractures and muscle weakness. It is caused by
      tumoral overproduction of fibroblast growth factor 23 (FGF23) that acts primarily
      at the proximal renal tubule, decreasing phosphate reabsorption and 1alpha
      hydroxylation of 25 hydroxyvitamin D, thus producing hypophosphatemia and
      osteomalacia. Lesions are typically small, benign mesenchymal tumors that may be
      found in bone or soft tissue, anywhere in the body. In up to 60% of these tumors,
      a fibronectin-1(FN1) and fibroblast growth factor receptor-1 (FGFR1) fusion gene
      has been identified that may serve as a tumoral driver. The diagnosis is
      established by the finding of acquired chronic hypophosphatemia due to isolated
      renal phosphate wasting with concomitant elevated or inappropriately normal blood
      levels of FGF23 and decreased or inappropriately normal 1,25-OH2-Vitamin D
      (1,25(OH)2D). Locating the tumor is critical, as complete removal is curative.
      For this purpose, a step-wise approach is recommended, starting with a thorough
      medical history and physical examination, followed by functional imaging.
      Suspicious lesions should be confirmed by anatomical imaging, and if needed,
      selective venous sampling with measurement of FGF23. If the tumor is not
      localized, or surgical resection is not possible, medical therapy with phosphate
      and active vitamin D is usually successful in healing the osteomalacia and
      reducing symptoms. However, compliance is often poor due to the frequent dosing
      regimen and side effects. Furthermore, careful monitoring is needed to avoid
      complications such us secondary/tertiary hyperparathyroidism, hypercalciuria, and
      nephrocalcinosis. Novel therapeutical approaches are being developed for TIO
      patients, such as image-guided tumor ablation and medical treatment with the anti
      FGF23 monoclonal antibody KRN23 or anti FGFR medications. The case of a patient
      with TIO is presented to illustrate the importance of adequate and appropriate
      evaluation of patients with bone pain and hypophosphatemia, as well as an step
      wise localization study of patients with suspected TIO.

PMID- 29021997
TI  - Dataset on the synthesis and characterization of boron fenbufen and its F-18
      labeled homolog.
AB  - The data presented in this article are related to the research article entitled
      "Synthesis and Characterization of Boron Fenbufen and its F-18 Labeled Homolog
      for Boron Neutron Capture Therapy of COX-2 Overexpressed Cholangiocarcinoma". The
      contents of the data article include 1) the set up for performing in vitro
      binding assay, 2) 1H-, 13C- and 19F-NMR of compounds described in main text, 3)
      HPLC chromatogram of the fluorination mixtures, 4) data of in vitro stability
      test, cell survival assay, western blot and PCR analysis, 5) the modules for
      fixing the two CCA rats for BNCT, and 6) bar diagram for tumor reduction using
      [18F]FDG-PET 24 h post treatment with BNCT.

PMID- 29021998
TI  - Dataset for the proteomic and transcriptomic analyses of perivitelline fluid
      proteins in Pomacea snail eggs.
AB  - This article describes how the proteomic and transcriptomic data were produced
      during a study of the reproductive proteins of Pomacea maculata, an aquatic apple
      snail laying colorful aerial eggs, and provides public access to the data. The
      data are related to a research article titled 'An integrated proteomic and
      transcriptomic analysis of perivitelline fluid proteins in a freshwater gastropod
      laying aerial eggs' (Mu et al., 2017) [1]. RNA was extracted from the albumen
      gland and other tissues and sequenced on an Illumina Hiseq. 2000. The assembled
      transcriptome was translated into protein sequences and then used for protein
      identification. Proteins from the perivitelline fluid of P. maculata were
      separated in SDS-PAGE and analyzed by LTQ-Orbitrap Elite coupled to an Easy-nLC.
      The translated transcriptome data are provided in this article. Proteomic data
      (.raw file format) are available via ProteomeXchange with the identifier
      PXD006718.

PMID- 29021999
TI  - Human performance data collected in a virtual environment.
AB  - This data article describes the experimental data used in the research article
      "Incorporating individual differences in human reliability analysis: an extension
      to the virtual experimental technique" (Musharraf et al., 2017) [1]. The article
      provides human performance data for 36 individuals collected using a virtual
      environment. Each participant was assigned to one of two groups for training: 1)
      G1: high level training and 2) G2: low level training. Participants' performance
      was tested in 4 different virtual scenarios with different levels of visibility
      and complexity. Several performance metrics of the participants were recorded
      during each scenario. The metrics include: time to muster, time spent running,
      interaction with fire doors and watertight doors, interaction with hazards, and
      reporting at different muster locations.

PMID- 29022000
TI  - Data on efficacy of umbelliferone on glycoconjugates and immunological marker in
      7,12-dimethylbenz(a)anthracene induced oral carcinogenesis.
AB  - Umbelliferone, a phenolic coumarin and dietary agent is believed to play a key
      role in pharmacological activities including anti-cancer and anti-oxidants effect
      in various in vitro and in vivo models. In present data on the pre-treatment of
      umbelliferone (30 mg/kg b.w.) for 16 weeks to 7,12-dimethylbenz(a)anthracene
      induced hamsters provides protection on cellular integrity by observing the
      status of cell surface glycoconjugates in the circulation and buccal mucosa and
      cytokeratin immunoexpression in the buccal mucosa of experimental animals. Data
      presented in this article brief that umbelliferone exhibits potent to clear cell
      surface abnormalities in buccal tissues and circulation during carcinogenesis and
      restored the expression of cytokeratin effect against 7,12
      dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis, which is
      attributes to its inhibitory role on glycoprotein synthesis or on the activity of
      the glycosyltransferase. In an article associates with this data set given the
      relevance to the research article entitled "Dose responsive efficacy of
      umbelliferone on lipid peroxidation, anti-oxidant, and xenobiotic metabolism in
      7,12-dimethylbenz(a)anthracene-induced oral carcinogenesis" namely Vijayalakshmi
      and Sindhu, 2017 assessed 100% tumour formation in 7,12-dimethylbenz(a)anthracene
      treated hamsters and oral administration of umbelliferone at a dose of 30 mg/kg
      b.w to 7,12-dimethylbenz(a)anthracene treated hamsters prevents tumour incidence,
      restores the status of the biochemical markers in circulation and buccal mucosa
      and also dysregulation in the expression of molecular markers. Given the
      relevance to this article entitled "Berberine protects cellular integrity during
      7,12-dimethylbenz[a]anthracene-induced oral carcinogenesis in golden Syrian
      hamsters" namely Sindhu and Manoharan 2010, which were based on spectrophotometry
      and florescence microscope analysis.

PMID- 29022001
TI  - Data supporting the functional role of Eleven-nineteen Lysine-rich Leukemia 3
      (ELL3) in B cell lymphoma cell line cells.
AB  - The data presented here are related to the research article entitled "Selective
      expression of the transcription elongation factor ELL3 in B cells prior to ELL2
      drives proliferation and survival" (Alexander et al., 2017) [1]. The cited
      research article characterizes Eleven-nineteen Lysine-rich Leukemia 3 (ELL3)
      expression in the B cell compartment and functional dependence in B lymphoma cell
      lines. This data report describes the mRNA expression pattern in a panel of cell
      lines representing the B cell compartment, supplementing the protein expression
      data presented in the associated research report. In addition, a reanalysis is
      presented of publicly available mRNA expression data from primary murine B cells
      to reveal dynamic regulation of the ELL family members post LPS stimulation
      (Barwick et al., 2016) [2]. The effect of ELL3 depletion on cell morphology,
      latent Epstein Barr Virus (EBV) lytic replication and differentiation markers in
      a Burkitt's lymphoma (BL) cell line cells are presented.

PMID- 29022002
TI  - Data on microcirculatory parameters of GTS- 21 treated rats assessed by
      intravital microscopy.
AB  - This article contains animal experimental data associated with the research
      article entitled "GTS-21 reduces microvascular permeability during experimental
      endotoxemia" (Schmidt et al., 2017) [1] (supplementary datasets of baseline
      intravital microscopic measurements, baseline TNF-alpha levels and vital
      parameters of the evaluated experimental groups are provided). Beneficial anti
      inflammatory effects of cholinergic mediators on microvascular inflammation have
      been demonstrated by intravital microscopic investigations (Schmidt et al., 2015)
      [2], therefore we evaluated the effect of the cholinergic mediator GTS-21 on
      microcirculatory alterations during endotoxemia [1]. The data regarding
      microcirculatory effects of GTS-21 treatment ((3-(2,4-Dimethoxybenzylidene)
      anabaseine dihydrochloride; 1 mg/kg; i.v.) in non-endotoxemic animals are
      presented in this article.

PMID- 29022003
TI  - Data on the effect of knockout of cytohesin-1 in myelination-related protein
      kinase signaling.
AB  - Cytohesin-1 is the guanine-nucleotide exchange factor of Arf6, a small GTPase of
      Arf family, and participates in cellular morphological changes. Knockout mice of
      cytohesin-1 exhibit decreased myelination of neuronal axons in the peripheral
      nervous system (PNS) "Phosphorylation of cytohesin-1 by Fyn is required for
      initiation of myelination and the extent of myelination during development
      (Yamauchi et al., 2012) [1]". Herein we provide the data regarding decreased
      phosphorylation levels of protein kinases involved in two major myelination
      related kinase cascades in cytohesin-1 knockout mice.

PMID- 29022004
TI  - Data related to dislocation density-based constitutive modeling of the tensile
      behavior of lath martensitic press hardening steel.
AB  - The data presented in this article are related to the research article entitled
      "On the plasticity mechanisms of lath martensitic steel" (Jo et al., 2017) [1].
      The strain hardening behavior during tensile deformation of a lath martensitic
      press hardening steel was described using a dislocation density-based
      constitutive model. The Kubin-Estrin model was used to describe strain hardening
      of the material from the evolution of coupled dislocation densities of mobile and
      immobile forest dislocation. The data presented provide insight into the complex
      deformation behavior of lath martensitic steel.

PMID- 29022006
TI  - Metastatic squamous cell carcinoma in a patient treated with adalimumab for
      hidradenitis suppurativa.

PMID- 29022005
TI  - Systemic and Terminal Ileum Mucosal Immunity Elicited by Oral Immunization With
      the Ty21a Typhoid Vaccine in Humans.
AB  - BACKGROUND & AIMS: Systemic cellular immunity elicited by the Ty21a oral typhoid
      vaccine has been extensively characterized. However, very limited data are
      available in humans regarding mucosal immunity at the site of infection (terminal
      ileum [TI]). Here we investigated the host immunity elicited by Ty21a
      immunization on terminal ileum-lamina propria mononuclear cells (LPMC) and
      peripheral blood in volunteers undergoing routine colonoscopy. METHODS: We
      characterized LPMC-T memory (TM) subsets and assessed Salmonella enterica serovar
      Typhi (S Typhi)-specific responses by multichromatic flow cytometry. RESULTS: No
      differences were observed in cell yields and phenotypes in LPMC CD8+-TM subsets
      following Ty21a immunization. However, Ty21a immunization elicited LPMC CD8+ T
      cells exhibiting significant S Typhi-specific responses (interferon-gamma, tumor
      necrosis factor-alpha, interleukin-17A, and/or CD107a) in all major TM subsets (T
      effector/memory [TEM], T-central/memory, and TEM-CD45RA+), although each TM
      subset exhibited unique characteristics. We also investigated whether Ty21a
      immunization elicited S Typhi-specific multifunctional effectors in LPMC CD8+
      TEM. We observed that LPMC CD8+ TEM responses were mostly multifunctional, except
      for those cells exhibiting the characteristics associated with cytotoxic
      responses. Finally, we compared mucosal with systemic responses and made the
      important observation that LPMC CD8+S Typhi-specific responses were unique and
      distinct from their systemic counterparts. CONCLUSIONS: This study provides the
      first demonstration of S Typhi-specific responses in the human terminal ileum
      mucosa and provides novel insights into the generation of mucosal immune
      responses following oral Ty21a immunization.

PMID- 29022007
TI  - Is uterine preservation combined with bilateral salpingo-oophorectomy to promote
      subsequent fertility safe in infiltrative mucinous ovarian cancer?
AB  - According to the latest World Health Organization classification (2014), mucinous
      ovarian cancers should be classified histologically as being either expansile or
      infiltrative. Compared to other epithelial cancers, both of these mucinous
      patterns are diagnosed, in the main, at an early stage, although they can affect
      relatively young patients. The infiltrative subtype is characterized by a
      morphologically and clinically more aggressive disease versus the expansile form.
      Consequently, even in young patients who would prefer fertility sparing
      management, the removal of both ovaries (even for a unilateral tumor) remains a
      common recommendation. However case reports describing the preservation of the
      uterus for a further potential pregnancy (following oocyte donation) have now
      been described. In this series, we present six patients treated for stage I
      mucinous infiltrative cancer using bilateral salpingo-oophorectomy with uterine
      preservation. All but one patient underwent 1-step (n = 1) or 2-step (n = 4)
      surgery, including peritoneal and nodal (4 patients) procedures. Disease stages
      were IA (n = 2), IC1 (n = 1), IC2 (n = 2), or IC3 (n = 1). While two patients
      subsequently became pregnant, two patients also suffered disease recurrence. For
      one patient, recurrence was at the pelvic peritoneum. For the second patient, an
      ultimately lethal disease recurrence involved the uterine serosa with nodal
      involvement. The results of this short series lead us to question the safety of
      this uterine-preserving strategy.

PMID- 29022009
TI  - Differential pulse voltammetric determination of salbutamol sulfate in syrup
      pharmaceutical formulation using poly(4-amino-3-hydroxynaphthalene sulfonic acid)
      modified glassy carbon electrode.
AB  - A new method for determination of salbutamol sulfate has been developed using
      poly(4-amino-3-hydroxynaphthalene sulfonic acid/GCE. Cyclic voltammetric
      investigation of the electrochemical behavior of salbutamol sulfate at the
      polymer modified glassy carbon unveiled electrocatalytic activity of the modifier
      towards irreversible oxidation of salbutamol sulfate. Dependence of peak current
      predominantly on scan rate than on square root of scan rate, and peak potential
      shift with pH demonstrated that oxidation of salbutamol sulfate at the polymer
      modified electrode follows adsorption reaction kinetics with proton
      participation. Under optimized solution and differential pulse voltammetric
      parameters, the oxidative peak current showed linear dependence on salbutamol
      sulfate concentration in the range 0.2 to 8 MUM with method detection limit
      (3s/m) and determination coefficient (R2) of 6.8 * 10-8 M and 0.99786,
      respectively. Low method detection limit, relatively wide linear range, and
      recovery results of spiked standard salbutamol sulfate in syrup samples in the
      range 96.7-98.9% validated the method for determination of salbutamol sulfate in
      pharmaceutical formulations. Differential pulse voltammetric analysis of
      salbutamol sulfate syrup formulation for its salbutamol sulfate content revealed
      98.8 to 99.3% of the labeled value confirming the applicability of the developed
      method for determination of salbutamol sulfate in real samples.

PMID- 29022008
TI  - Inflammatory activation of human cardiac fibroblasts leads to altered calcium
      signaling, decreased connexin 43 expression and increased glutamate secretion.
AB  - Cardiac fibroblasts, which are abundant in heart tissue, are involved not only in
      extracellular matrix homeostasis and repair, but also in cardiac remodeling after
      a myocardial infarction that, in turn, can lead to loss of cardiac function and
      heart failure. Ca2+ signaling is functionally important in many cell types, but
      the roles of fibroblast signaling and inflammation in the pathogenesis of heart
      disease are unclear. Here, we tested the hypothesis that inflammatory activation
      affects cardiac fibroblasts, both in terms of Ca2+ signaling and their capacity
      for intercellular communication through the gap junction channel protein connexin
      43 (Cx43). We examined Ca2+ responses induced by known modulators of cardiac
      function such as glutamate, ATP and 5-hydroxytryptamine (5-HT) in human cardiac
      fibroblasts, under normal and inflammatory conditions. We showed that activation
      of human cardiac fibroblasts by lipopolysaccharide (LPS) for 24 h altered Ca2+
      signaling, increased TLR4 and decreased Cx43 expression. In the fibroblasts, LPS
      treatment increased glutamate-evoked and decreased 5-HT-evoked Ca2+ signals. LPS
      activation also induced increased secretion of glutamate and proinflammatory
      cytokines from these cells. In summary, we propose that inflammatory stimuli can
      affect intracellular Ca2+ release, Cx43 expression, glutamate release and
      cytokine secretion in human cardiac fibroblasts. Inflammatory conditions may,
      therefore, impair intercellular network communication between fibroblasts and
      cardiomyocytes potentially contributing to cardiac dysfunction.

PMID- 29022010
TI  - The effect of cold acclimation on the low molecular weight carbohydrate
      composition of safflower.
AB  - Understanding cold acclimation and identifying the low molecular weight
      carbohydrates that support the development of freezing tolerant safflower
      seedlings will aid in breeding winter-hardy cultivars for temperate cropping
      systems. Three field selected lines of winter safflower (WSRC01: PI 651878;
      WSRC02: PI 651879; WSRC03: PI 651880) were cold acclimated for four weeks at 4 
      degrees C and compared to seedlings grown for two weeks at 20  degrees C. The
      commercial spring-type cultivar, Ole, served as a non-hardy check. Leaf, stem,
      and root fructose, glucose, sucrose, raffinose, and stachyose concentrations all
      increased to variable extents across the PI accessions after cold acclimation. In
      comparison with Ole, winter safflower accessions tended to be more responsive to
      cold acclimation by increasing metabolite concentration. Verbascose was only
      recovered within leaf tissue and PI 651880 was the only entry to show a
      substantial alteration in verbascose concentration due to cold acclimation. Based
      on these data, no specific low molecular carbohydrate was responsive or
      responsible for the accumulation of freezing tolerance, but a concert of
      metabolites and their responsiveness may help explain the observed differences in
      development, freezing tolerance, and ultimately winterhardiness among safflower
      germplasm.

PMID- 29022012
TI  - Vanadate oxidative and apoptotic effects are mediated by the MAPK-Nrf2 pathway in
      layer oviduct magnum epithelial cells.
AB  - Vanadium is a metal of high physiological, environmental and industrial
      importance. However, vanadium-induced oxidative stress can reduce the egg quality
      of poultry, and be potentially harmful to humans, and the underlying mechanism is
      not clear. In this study, we investigated the underlying relationship between the
      oxidant-sensitive mitogen-activated protein kinase (MAPK) signaling pathway and
      vanadium-induced oxidative stress in oviduct magnum epithelial (OME) cells.
      Cultured OME cells were treated with 100 MUmol L-1 vanadium and/or MAPK
      inhibitors [P38 MAPK inhibitor, SB203580; extracellular regulated protein kinase
      1 and 2 (ERK1/2) inhibitor, U0126; c-JUN N-terminal kinases (JNK) inhibitor,
      SP600125]. Cell viability, apoptosis, and generation of reactive oxygen species
      (ROS) were assessed using flow cytometry. The expression of oxidative stress
      related genes and their proteins was measured by reverse transcription-polymerase
      chain reaction and western blotting. Vanadium treatment reduced cell viability,
      whereas pretreated OME cells with SB203580 and U0126 prevented the reducing
      effect of vanadium on cell viability (P < 0.05). Likewise, MAPK inhibitors
      effectively suppressed vanadium-induced apoptosis and ROS generation (P < 0.05).
      In the OME cells treated with vanadium, SB203580 (P < 0.05) and SP600125 (P =
      0.08) increased catalase activity by 89.3% and 55.3%; SB203580 and U0126
      increased (P < 0.05) glutathione peroxidase activity by 44.9% and 51.1%,
      respectively. Incubation of OME cells with MAPK inhibitors also prevents
      malondialdehyde concentration increase and lactic dehydrogenase activity decrease
      in response to vanadium (P < 0.05). Vanadium downregulated P38, ERK1/2, JNK,
      Nrf2, sMaf, GCLC, NQO1 and HO-1 mRNA expression (P < 0.05). In contrast,
      inhibition of JNK with SP600125 upregulated P38, ERK1/2, JNK, Nrf2, GCLC and HO-1
      mRNA expression (P < 0.05); inhibition of P38 with SB203580 upregulated JNK, NQO1
      and HO-1 mRNA expression (P < 0.05); and inhibition of ERK1/2 with U0126
      upregulated ERK1/2, GCLC and HO-1 mRNA expression (P < 0.05). Moreover,
      phosphorylation of P38, ERK1/2, JNK, and Nrf2 proteins was enhanced by V
      incubation; however, SP600125 blocked the phosphorylation of these proteins,
      whereas SB203580 blocked the phosphorylation of P38 and Nrf2. These results
      indicate that vanadium inducing oxidative stress in OME cells might be, at least,
      associated with the phosphorylation of the P38MAPK/JNK-Nrf2 pathway, which
      reduces the expression of phase II detoxifying enzymes.

PMID- 29022011
TI  - Placental extract ameliorates non-alcoholic steatohepatitis (NASH) by exerting
      protective effects on endothelial cells.
AB  - Non-alcoholic steatohepatitis (NASH) is a severe form of fatty liver disease that
      is defined by the presence of inflammation and fibrosis, ultimately leading to
      cirrhosis and hepatocellular carcinoma. Treatment with human placental extract
      (HPE) reportedly ameliorates the hepatic injury. We evaluated the effect of HPE
      treatment in a mouse model of NASH. In the methione- and choline-deficient (MCD)
      diet-induced liver injury model, fibrosis started from regions adjacent to the
      sinusoids. We administered the MCD diet with high-salt loading (8% NaCl in the
      drinking water) to mice deficient in the vasoprotective molecule RAMP2 for 5
      weeks, with or without HPE. In both the HPE and control groups, fibrosis was seen
      in regions adjacent to the sinusoids, but the fibrosis was less pronounced in the
      HPE-treated mice. Levels of TNF-alpha and MMP9 expression were also significantly
      reduced in HPE-treated mice, and oxidative stress was suppressed in the
      perivascular region. In addition, HPE dose-dependently increased survival of
      cultured endothelial cells exposed to 100 MUM H2O2, and it upregulated expression
      of eNOS and the anti-apoptotic factors bcl-2 and bcl-xL. From these observations,
      we conclude that HPE ameliorates NASH-associated pathologies by suppressing
      inflammation, oxidative stress and fibrosis. These beneficially effects of HPE
      are in part attributable to its protective effects on liver sinusoidal
      endothelial cells. HPE could thus be an attractive therapeutic candidate with
      which to suppress progression from simple fatty liver to NASH.

PMID- 29022014
TI  - Quantifying the dispersion quality of partially aggregated colloidal dispersions
      by high frequency rheology.
AB  - An important parameter for the performance of nanomaterials is the degree by
      which the nanoparticles are dispersed in a matrix. Optical microscopy or
      scattering methods are useful to characterise the state of dispersion, but are
      not generally applicable to all materials. Electron microscopy methods are
      laborious in preparation and typically offer only quantitative information on a
      very local scale. In the present work we investigate how high frequency
      rheological measurements can be used for partially dispersed suspensions at
      intermediate to higher particle loadings, even for high viscous matrices.
      Although the contribution of the particles is particularly visible in the low
      frequency linear viscoelastic behaviour, a more direct relationship between
      rheological properties and degree of dispersion can be derived from the loss
      modulus in the high frequency limit. To this end, a home-built piezo shear
      rheometer is constructed to extend the frequency range typically accessible by
      commercial rotational rheometers. Measurements on spherical silica particles,
      with a varying degree of dispersion in low molecular weight PDMS, are used to
      demonstrate how high frequency rheometry can be used to quantify dispersion
      quality. The linear viscoelastic properties are compared to analytical scaling
      theories to demonstrate that a hydrodynamically dominated regime is reached. The
      dependence of the relative high frequency loss modulus on volume fraction is then
      compared to predictions of a hydrodynamic viscosity model for the derivation of a
      dispersion quality index. It is used to follow the evolution of the dispersion
      quality as a function of mixing time and consumed power.

PMID- 29022013
TI  - Luminescence, energy transfer and optical thermometry of a novel narrow red
      emitting phosphor: Cs2WO2F4:Mn4.
AB  - A novel red emitting Cs2WO2F4:Mn4+ phosphor was successfully synthesized by a two
      step wet chemical method. The crystal structure, morphology, and elemental
      composition were confirmed by powder X-ray diffraction (XRD), transmission
      electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS),
      respectively. The luminescence properties were investigated from emission,
      excitation and luminescence decay curves in the temperature region of 10-500 K.
      The application of non-contact optical thermometry of Cs2WO2F4:Mn4+ based on the
      fluorescence intensity ratio (FIR) of the two coupled anti-Stokes and Stokes
      sidebands is discussed. The as-prepared Cs2WO2F4:Mn4+ phosphor shows a bright
      narrow red emission at 632 nm under excitation by a blue lamp at 470 nm and it
      also presents a broad and yellow-white intrinsic tungstate emission (~520 nm)
      under UV excitation. The mechanism of energy transfer from [WO2F4]2- (the
      sensitizer) to Mn4+ (the activator) is discussed.

PMID- 29022015
TI  - Silylation of O-H bonds by catalytic dehydrogenative and decarboxylative coupling
      of alcohols with silyl formates.
AB  - The silylation of O-H bonds is a useful methodology in organic synthesis and
      materials science. While this transformation is commonly achieved by reacting
      alcohols with reactive chlorosilanes or hydrosilanes, we show herein for the
      first time that silylformates HCO2SiR3 are efficient silylating agents for
      alcohols, in the presence of a ruthenium molecular catalyst.

PMID- 29022016
TI  - Structuralization of magnetic nanoparticles in 5CB liquid crystals.
AB  - This work is devoted to the study of highly stable composite systems of the
      liquid crystal 4-n-pentyl-4'-cyanobiphenyl (5CB) doped with CoFe2O4 magnetic
      nanoparticles. Ferronematic samples were prepared with two different weight
      concentrations: sample A 0.085 wt% and sample B 0.062 wt%. The interaction of
      CoFe2O4 nanoparticles with the liquid crystal was investigated by small-angle X
      ray-scattering and magnetization measurements. The obtained results reveal
      aggregates formed by magnetic nanoparticles that are oriented in the nematic
      phase. Moreover, the prepared samples show unexpected behaviour of a sudden
      change in magnetization, which is unusual for such ferronematics.

PMID- 29022017
TI  - Structure-property relationships in protic ionic liquids: a study of solvent
      solvent and solvent-solute interactions.
AB  - The ionic nature of a functionalized protic ionic liquid cannot be rationalized
      simply through the differences in aqueous proton dissociation constants between
      the acid precursor and the conjugate acid of the base precursor. The extent of
      proton transfer, i.e. the equilibrium ionicity, of a tertiary ammonium acetate
      protic ionic liquid can be significantly increased by introducing an hydroxyl
      functional group on the cation, compared to the alkyl or amino-functionalized
      analogues. This increase in apparent ionic nature correlates well with variations
      in solvent-solute and solvent-solvent interaction parameters, as well as with
      physicochemical properties such as viscosity.

PMID- 29022018
TI  - Versatile design and synthesis of nano-barcodes.
AB  - Encoded nano-structures/particles have been used for barcoding and are in great
      demand for the simultaneous analysis of multiple targets. Due to their nanoscale
      dimension(s), nano-barcodes have been implemented favourably for bioimaging, in
      addition to their security and multiplex bioassay application. In designing nano
      barcodes for a specific application, encoding techniques, synthesis strategies,
      and decoding techniques need to be considered. The encoding techniques to
      generate unique multiple codes for nano-barcodes are based on certain encoding
      elements including optical (fluorescent and non-fluorescent), graphical,
      magnetic, and phase change properties of nanoparticles or their different shapes
      and sizes. These encoding elements can generally be embedded inside, decorated on
      the surface of nanostructures or self-assembled to prepare the nano-barcodes. The
      decoding techniques for each encoding technique are different and need to be
      suitable for the desired applications. This review will provide a thorough
      discussion on designing nano-barcodes, focusing on the encoding techniques,
      synthesis methods, and decoding for applications including bio-detection,
      imaging, and anti-counterfeiting. Additionally, associated challenges in the
      field and potential solutions will also be discussed. We believe that a
      comprehensive understanding on this topic could significantly contribute towards
      the advancement of nano-barcodes for a broad spectrum of applications.

PMID- 29022019
TI  - Experimental verification of simultaneous desalting and molecular
      preconcentration by ion concentration polarization.
AB  - While the ion concentration polarization (ICP) phenomenon has been intensively
      researched for the last decade, a complete picture of ion and analyte
      distributions near nanoporous membranes is strongly desired, not only for
      fundamental nano-electrokinetic studies but also for the development of lab-on-a
      chip applications. Since direct concentration measurements, using either time
      consuming collection or microelectrodes, are limited due to low throughput (<nL
      min-1 in typical micro/nanofluidic device) and Faradaic reactions, respectively,
      we measured the concentration changes of prefilled solutions in individual
      reservoirs in this work. As a result, analytes larger than the size of nanopores
      were completely repelled by the ICP layer, 65% of cations were transported
      through the nanoporous membrane to sustain the ICP phenomenon, and the remaining
      anions were consumed by electrode reactions for electro-neutrality requirements.
      These combined effects would enable the perfect recovery of a target analyte and
      the removal of unnecessary salts simultaneously. Using this scenario, the novel
      concept of an ink recycler was also demonstrated in this work. We showed that 40%
      of unnecessary salt, which causes serious deterioration of inkjet heads, was
      removed, while the concentration of ink molecules was doubled in a single-step
      operation. This simultaneous desalting and molecular preconcentration mechanism
      would be a key operational strategy of various refinery/purification applications
      for drug discovery and the chemical industry, etc.

PMID- 29022020
TI  - Weak C-HF-C hydrogen bonds make a big difference in graphane/fluorographane and
      fluorographene/fluorographane bilayers.
AB  - Using density functional theory computations with van der Waals (vdW)
      corrections, we reveal that C-HF-C hydrogen bonding exists in
      graphane/fluorographene and fluorographane/fluorographane bilayers. The
      significant C-HF-C hydrogen bonding is strong enough to combine two separate
      monolayers to form the bilayer. Interestingly, both the graphane/fluorographene
      and fluorographane/fluorographane bilayers are metallic in the most stable
      stacking configuration. Applying a perpendicular electric field can effectively
      open a bandgap for both bilayers, and we found that the field-induced gap opening
      for both graphane/fluorographene and fluorographane/fluorographane bilayers can
      be enhanced by biaxial tensile strain. These results are expected to aid in the
      design of novel electronic and optoelectronic devices based on graphene
      materials, and they highlight the use of weak interactions for modulating band
      structures in two-dimensional materials.

PMID- 29022021
TI  - Channel-facilitated molecule and ion transport across polymer composite
      membranes.
AB  - Biological membranes possess hierarchical channels and thus exhibit ultrahigh
      permselectivity for molecules and ions. Intrigued by the delicate structure and
      transport mechanisms in biochannels, polymer composite membranes with selective
      transport channels are successfully fabricated for diverse energy- and
      environment-related applications. This tutorial review aims to present the latest
      progress in the design and construction of selective molecule/ion transport
      channels within polymer composite membranes with emphasis on the regulation of
      the physical and chemical microenvironments of these channels. The concluding
      remarks are presented with a tentative perspective on the future research and
      development of highly efficient channel-facilitated molecule/ion transport across
      polymer composite membranes.

PMID- 29022022
TI  - Physicochemical and electrochemical characterisation of imidazolium based IL +
      GBL mixtures as electrolytes for lithium-ion batteries.
AB  - Ionic liquid/organic solvent mixtures are investigated as potential optimal
      electrolytes for lithium-ion batteries (LIBs) that can combine low flammability,
      good thermal stability and high electrical conductivity. In this work the
      standard ionic association constants of different 1-alkyl-3-methylimidazolium
      ([Cnmim]+, n is the number of C in the alkyl side chain - 2, 4, 6 or 8) TFSI-
      based ionic liquids (ILs) in gamma-butyrolactone (GBL) are determined using the
      low concentration Chemical Model (lcCM). Based on the values of for ILs in GBL
      and earlier physicochemical systematic investigations in that solvent, the system
      with the lowest was selected for the preparation of the LiTFSI/C2mimTFSI/GBL
      electrolyte for testing TiO2 nanotube arrays as anode material for LIBs. In an
      attempt to realize LIBs with enhanced safety, we report herein a comparative
      study of the electrochemical properties of LiTFSI/C2mimTFSI/GBL and an
      electrolyte containing an IL without acidic C(2)H on the imidazolium cation,
      namely, LiTFSI/C2mmimTFSI/GBL. The presence of GBL can improve the reduction
      stability of imidazolium-based ILs and GBL in LiTFSI/IL/GBL-based electrolytes.
      It was shown that TiO2 nanotube structures display stable galvanostatic cycling
      in the LiTFSI/C2mimTFSI/GBL electrolyte after 350 full (dis-)charge cycles and
      after cell exposure to T = 328.15 K.

PMID- 29022026
TI  - Highlights from the Faraday Discussion: Halogen Bonding in Supramolecular and
      Solid State Chemistry, July 10-12th 2017, Ottawa, Canada.

PMID- 29022027
TI  - The first successful observation of in-cell NMR signals of DNA and RNA in living
      human cells.
AB  - In order to understand intracellular biological events, information on the
      structure, dynamics and interaction of proteins and nucleic acids in living cells
      is of crucial importance. In-cell NMR is a promising method to obtain this
      information. Although NMR signals of proteins in human cells have been reported,
      those of nucleic acids were reported only in Xenopus laevis oocytes, i.e., not in
      human cells. Here, DNA and RNA were introduced into human cells by means of pore
      formation by bacterial toxin streptolysin O and subsequent resealing. Then, NMR
      signals of DNA and RNA were successfully observed for the first time in living
      human cells. The observed signals directly suggested the formation of DNA and RNA
      hairpin structures in living human cells.

PMID- 29022032
TI  - The Ethics of Medical Education - The Ethical and Professional Issues in Teaching
      and Learning Medicine.

PMID- 29022034
TI  - Mindfulness: A New Paradigm of Psychosocial Care in the Palliative Care Setting
      in Southeast Asia.
AB  - Alleviation of suffering in palliative care needs a combination of good symptom
      control and psychosocial care. The capacity of mindfulness to promote
      psychological flexibility opens up possibilities of creating a paradigm shift
      that can potentially change the landscape of psychosocial care. In this review,
      we attempt to introduce 4 methods to establish mindfulness based on 'The
      Discourse on the Foundations of Mindfulness', a core text of Theravada Buddhism,
      followed by a brief comparison of the concepts and practices of mindfulness in
      different cultures and religions in Southeast Asia. Next, 2 mindfulness-based
      interventions specifically designed for palliative psychosocial care -
      mindfulness-based supportive therapy (MBST) and mini-mindfulness meditation (MMM)
      are introduced. We hypothesise that mindful practices, tailored to the palliative
      setting, can promote positive psychosocial outcomes.

PMID- 29022033
TI  - Improved Survival of Advanced Lung Cancer in Singapore Over the Past Decade.
AB  - INTRODUCTION: We reviewed changes in clinical characteristics, treatment and
      survival of lung cancer patients in Singapore over the past decade. MATERIALS AND
      METHODS: We reviewed all primary lung cancer cases from January 2004 to December
      2013. Basic demographic, clinical and treatment data were extracted from the
      database. Overall survival (OS) was calculated using Kaplan-Meier method;
      survival curves were compared using log-rank test. Linear regression trend lines
      were estimated using least squares approach, and Cox regression analyses were
      performed to identify prognostic factors. RESULTS: Among 6006 lung cancer
      patients, the median age was 68 years old, 65% were males, 88% were Chinese, 92%
      had non-small-cell lung cancer and 76% had advanced stage IIIB/IV. There were
      proportionally more adenocarcinomas diagnosed over the years, while that of
      squamous cell carcinoma (SCC) and small-cell-lung cancer (SCLC) have remained
      stable. The median OS of all patients increased from 9.2 months in 2004 to 11.5
      months in 2013. This survival improvement was statistically significant among
      patients with stage IIIB/IV (6.7 to 8.7 months; P = 0.005) and adenocarcinoma
      (12.7 to 15.4 months; P = 0.041). There was no improvement in median OS for SCC
      or SCLC. The use of epidermal growth factor receptor tyrosine kinase inhibitors
      (EGFR TKI) (hazard ratio [HR] 0.68; 95% CI, 0.63 to 0.73) and pemetrexed (HR,
      0.69; 95% CI, 0.63 to 0.76) were significantly associated with improved OS.
      CONCLUSION: Survival of patients with advanced stage IIIB/IV lung adenocarcinoma
      has improved over the past decade, and is potentially associated with the use of
      EGFR TKI and pemetrexed.

PMID- 29022035
TI  - From Bolam-Bolitho to Modified-Montgomery - A Paradigm Shift in the Legal
      Standard of Determining Medical Negligence in Singapore.
AB  - In a recent landmark litigation, the Singapore Court of Appeal introduced a new
      legal standard for determining medical negligence with regards to information
      disclosure - the Modified-Montgomery test. This new test fundamentally shifts the
      legal position concerning the standard of care expected of a doctor when he
      dispenses medical advice. Previously, a doctor is expected to disclose what a
      "reasonable physician" would tell his patient. Now, a doctor must disclose "all
      material risks" that a "reasonable patient" would want to know under his unique
      circumstances. Patient-centred communication is no longer an aspirational ideal
      but has become a legal mandate. Manpower, administrative, logistic and medical
      educational reforms should start now, so as to support the average physician
      transit from the era of the Bolam-Bolitho, to that of the Modified-Montgomery.

PMID- 29022036
TI  - A Case of Bilateral Atypical Ulnar Fractures with Bisphosphonate Therapy in a
      Walking Aided Elderly.

PMID- 29022037
TI  - Liquorice-Induced Severe Hypokalaemic Rhabdomyolysis with Acute Kidney Injury.

PMID- 29022038
TI  - 23rd Gordon Arthur Ransome Oration: Law and Medicine: Professions of Honour,
      Service and Excellence.
AB  - Amidst dramatic global change, there is a greater need than ever for principled
      and committed professionals. The sibling professions of law and medicine, in
      particular, serve crucial functions in contemporary society. To meet the
      challenges of the future, members of both professions must appreciate and commit
      to their shared calling to public service, and ensure that it is not overridden
      by the profit motive. Three further commitments follow from this: first, to
      nurture and mentor new entrants to the professions to ensure the continuance of
      that mission of public service; second, to improve accessibility and
      affordability through pro bono work and by other means, so that all who need
      professional assistance can receive it; and, thirdly, to serve with excellence in
      ethics as well as competence, so as not to betray the trust of the laypersons who
      rely on professionals to safeguard their interests and welfare. The medical and
      legal professions have much to learn and gain from working with each other toward
      those shared goals.

PMID- 29022039
TI  - Paediatric supracondylar humeral fractures: a technique for safe medial pin
      passage with zero incidence of iatrogenic ulnar nerve injury.
AB  - INTRODUCTION: The cross Kirschner wire (K-wire) configuration in closed reduction
      and percutaneous pinning of paediatric supracondylar humeral fracture affords
      superior stability. However, medial pin placement presents a risk of iatrogenic
      ulnar nerve injury. This study describes, in step-by-step detail, another safe
      method of percutaneous medial pin insertion. METHODS: The technique involved
      placing the patient's arm in external rotation, with elbow flexed no more than 45
      degrees  after closed reduction. The surgeon held the K-wire close to its sharp
      end to pass it percutaneously onto the medial epicondyle, then adjusted his grip
      toward the blunt end. After fluoroscopy check, the wire driver was engaged and an
      anteriorly directed force was applied to the distal humerus fragment using the
      thumb of the surgeon's free hand. The K-wire was inserted at a 45 degrees  angle
      to the longitudinal axis of the humerus shaft. Clinical notes and radiographs of
      patients who underwent surgery with this technique from 2006 to 2008 were
      reviewed. RESULTS: A total of 125 patients (84 boys, 41 girls) were included,
      with a mean age of 7.1 (range 2-14) years. Most injuries were left-sided (72.8%,
      n = 91, vs. right: 27.2%, n = 34). 72 (57.6%) patients had two-pin cross K-wire
      configuration, while 53 (42.4%) patients had an additional lateral pin inserted.
      No patient had postoperative ulnar neuropathy. There were no complications of non
      union, malunion or infection. CONCLUSION: This safe method of medial pin
      placement for surgical stabilisation of paediatric supracondylar humeral
      fractures is easily learnt and reproducible, and produces excellent results.

PMID- 29022040
TI  - Short-term outcomes of patients with Type 2 diabetes mellitus treated with
      canagliflozin compared with sitagliptin in a real-world setting.
AB  - INTRODUCTION: We aimed to evaluate the effectiveness and safety of canagliflozin
      as compared to sitagliptin in a real-world setting among multiethnic patients
      with Type 2 diabetes mellitus (T2DM) in Singapore. METHODS: This was a new-user,
      active-comparator, single-centre retrospective cohort study. Patients aged 18-69
      years with T2DM and estimated glomerular filtration rate >= 60 mL/min/1.73 m2
      were eligible for inclusion if they were initiated and maintained on a steady
      daily dose of canagliflozin 300 mg or sitagliptin 100 mg between 1 May and 31
      December 2014, and followed up for 24 weeks. RESULTS: In total, 57 patients
      (canagliflozin 300 mg, n = 22; sitagliptin 100 mg, n = 35) were included. The
      baseline patient characteristics in the two groups were similar, with overall
      mean glycated haemoglobin (HbA1c) of 9.4% +/- 1.4%. The use of canagliflozin 300
      mg was associated with greater reductions in HbA1c (least squares [LS] mean
      change -1.6% vs. -0.4%; p < 0.001), body weight (LS mean change -3.0 kg vs. 0.2
      kg; p < 0.001) and systolic blood pressure (LS mean change: -9.7 mmHg vs. 0.4
      mmHg; p < 0.001), as compared with sitagliptin 100 mg. About half of the patients
      on canagliflozin 300 mg reported mild osmotic diuresis-related side effects that
      did not lead to drug discontinuation. CONCLUSION: Our findings suggest that
      canagliflozin was more effective than sitagliptin in reducing HbA1c, body weight
      and systolic blood pressure in patients with T2DM, although its use was
      associated with an increased incidence of mild osmotic diuresis-related side
      effects.

PMID- 29022041
TI  - Empathy and burnout: a study on residents from a Singapore institution.
AB  - INTRODUCTION: Empathy and burnout are two entities that are important in a
      physician's career. They are likely to relate to each other and can be heavily
      influenced by surrounding factors, such as medical education, local practices and
      cultural expectations. To our knowledge, empathy and burnout studies have not
      been performed in Singapore. This study was designed to evaluate empathy and
      burnout levels using the Jefferson Scale of Physician Empathy (JSPE) and Maslach
      Burnout Inventory (MBI) among residents in Singapore, and compare them with the
      United States (US) literature. METHODS: The JSPE, MBI and a self-designed
      questionnaire were completed by 446 trainees at a residency-sponsoring
      institution in Singapore. RESULTS: Residents in Singapore had lower empathy and
      higher rates of burnout compared to US literature. Physician empathy was
      associated with burnout: residents with higher empathy scores had higher personal
      accomplishment (p < 0.001, r = 0.477, r2 = 0.200); and lower emotional exhaustion
      (p < 0.001, r = 0.187, r2 = 0.035) and depersonalisation (p < 0.001, r = 0.321,
      r2 = 0.103) scores. CONCLUSION: Residents in Singapore had lower empathy and
      higher burnout scores compared to the US literature. Further research into the
      underlying cause is imperative to guide intervention.

PMID- 29022042
TI  - Erratum to: Delayed post-operative tension pneumocephalus and pneumorrhachis.
AB  - Unfortunately, two author names were missed out in author group of the original
      publication.

PMID- 29022043
TI  - Letter to the Editor concerning "Scoliosis convexity and organ anatomy are
      related" by T. P. C. Schlosser et al. (Eur Spine J; 2017: doi:10.1007/s00586-017
      4970-5).

PMID- 29022044
TI  - Erratum to: Action and function of Wnt/beta-catenin signaling in the progression
      from chronic hepatitis C to hepatocellular carcinoma.
AB  - Erratum to: J Gastroenterol (2017) 52:419-431 DOI 10.1007/s00535-016-1299-5.

PMID- 29022045
TI  - Author Correction: Molecular basis of mycobacterial survival in macrophages.
AB  - One of the author affiliations was missed to include in the original publication.
      The correct information is given below.

PMID- 29022047
TI  - Bilateral common iliac artery aneurysms as cause of renal failure.

PMID- 29022046
TI  - [Radium-223 dichloride in patients with castration-refractory prostate cancer].
AB  - Since November 2013, the alpha emitter radium-223 dichloride
      (Alpharadin/Xofigo(r)) has been approved for the treatment of men with castration
      resistant prostate cancer (CRPC) with symptomatic bone metastases and no known
      visceral metastatic disease. In the ASYMPCA clinical trial, radium-223 was shown
      to improve overall survival and to reduce the time to the first symptomatic
      skeletal event. The use of radium-223 was associated with a reduction of pain and
      an improvement of health-related quality of life compared to the placebo arm. The
      efficacy of radium-223 dichloride was not inhibited by the use of chemotherapy
      with docetaxel. Studies have demonstrated a longer overall survival (OS) in
      patients with a combined treatment of abiraterone or enzalutamide; however, until
      this data is validated in larger clinical trials, the combination of radium-223
      and abiraterone/enzalutamide cannot be recommended. Patients who have received
      concomitant medication with denosumab appeared to have a longer OS compared to
      patients who did not. A second treatment cycle of radium-223 was not associated
      with any adverse events when compared to the outcomes reported in the ASLYMPCA
      trial. Here the median radiographic progression-free survival was 9 months.

PMID- 29022048
TI  - Acute respiratory failure from esophageal dilatation.

PMID- 29022051
TI  - [Pigmentation disorders].

PMID- 29022050
TI  - Concurrent radiotherapy with temozolomide vs. concurrent radiotherapy with a
      cisplatinum-based polychemotherapy regimen : Acute toxicity in pediatric high
      grade glioma patients.
AB  - PURPOSE: As the efficacy of all pediatric high-grade glioma (HGG) treatments is
      similar and still disappointing, it is essential to also investigate the toxicity
      of available treatments. METHODS: Prospectively recorded hematologic and
      nonhematologic toxicities of children treated with radiochemotherapy in the HIT
      GBM-C/D and HIT-HGG-2007 trials were compared. Children aged 3-18 years with
      histologically proven HGG (WHO grade III and IV tumors) or unequivocal radiologic
      diagnosis of diffuse intrinsic pontine glioma (DIPG) were included in these
      trials. The HIT-HGG-2007 protocol comprised concomitant radiochemotherapy with
      temozolomide, while cisplatinum/etoposide (PE) and PE plus ifosfamide (PEI) in
      combination with weekly vincristine injections were applied during
      radiochemotherapy in the HIT GBM-C/D protocol. RESULTS: Regular blood counts and
      information about cellular nadirs were available from 304 patients (leukocytes)
      and 306 patients (thrombocytes), respectively. Grade 3-4 leukopenia was much more
      frequent in the HIT GBM-C/D cohort (n = 88, 52%) vs. HIT-HGG-2007 (n = 13, 10%; P
      <0.001). Grade 3-4 thrombopenia was also more likely in the HIT GBM-C/D cohort (n
      = 21, 12% vs. n = 3,2%; P <0.001). Grade 3-4 leukopenia appeared more often in
      children aged 3-7 years (n = 38/85, 45%) than in children aged 8-12 years (n =
      39/120, 33%) and 13-18 years (24/100, 24%; P =0.034). In addition, sickness was
      more frequent in the HIT GBM-C/D cohort (grade 1-2: 44%, grade 3-4: 6% vs. grade
      1-2: 28%, grade 3-4: 1%; P <0.001). CONCLUSION: Radiochemotherapy involving
      cisplatinum-based polychemotherapy is more toxic than radiotherapy in combination
      with temozolomide. Without evidence of differences in therapeutic efficacy, the
      treatment with lower toxicity, i. e., radiotherapy with temozolomide should be
      used.

PMID- 29022052
TI  - Was endothermy in amniotes induced by an early stop in growth during ontogeny?
AB  - Endothermy and its evolution are still an unresolved issue. Here, we present a
      model which transforms an ectothermic amniote (ancestor) into a derived amniote
      (descendant) showing many characteristics seen in extant endothermic birds and
      mammals. Consistent with the fossil record within the ancestral lineages of birds
      and mammals, the model assumes that mutations in genes which get active during
      ontogeny and affect body growth resulted in a reduced asymptotic body size and an
      early growth stop of the descendant. We show that such a postulated early growth
      stop in the descendant simultaneously increases the growth rate and metabolic
      rate, and also changes six life history traits (offspring mass, annual
      clutch/litter mass, number of offspring per year, age and mass at which sexual
      maturity is reached, age at which the individual is fully grown) of the
      descendant compared to a similar-sized ancestor. All these changes coincide with
      known differences between recent ectothermic and endothermic amniotes. We also
      elaborate many other differences and similarities in biological characteristics
      supporting the early growth stop. An early stop in growth during ontogeny thus
      could have played a key role in the evolution of endothermy within the reptilia
      and therapsids. It generated variability in characteristics of ancestral
      ectotherms, which was subject to natural selection in the past and resulted in
      many adaptations linked to endothermy in today's birds and mammals.

PMID- 29022053
TI  - Glycated albumin (GA) and inflammation: role of GA as a potential marker of
      inflammation.
AB  - AIMS: Abnormal levels of glycated albumin (GA) are associated with the onset of
      both diabetes and inflammation. Although inflammation has long been associated
      with diabetes, this article aims to explore the underlying mechanisms of this
      relationship as it pertains to the role of GA. METHODS: We have reviewed 52
      research articles since the year 2000. Common search terms used were
      "(inflammatory mediator) and GA" or "inflammation and GA". The findings have been
      organized according to diabetic complications with respect to the interactions of
      GA and inflammatory mediators. Glycated albumin and specific inflammatory
      mediators have been reported to play various roles in the pathogenesis of insulin
      resistance, atherosclerosis, coronary artery disease, retinopathy, and
      nephropathy. In the case of nephropathy and recently retinopathy, there is
      considerable evidence for GA in concert with inflammation playing a direct role
      in organ pathology. There is copious literature detailing GA's involvement in
      stimulating inflammatory markers and certain pro-inflammatory cytokines. A recent
      clinical study has shown GA to be a marker for inflammation in non-diabetic
      rheumatoid arthritis patients with the significance of standard inflammatory
      markers. CONCLUSIONS: The clinical utility of GA measurement may likely reside in
      its versatility as both a mediator of inflammation as well as a marker to track
      hyperglycemia and other diabetes complications. Further understanding of the role
      GA plays in glycemic and inflammatory diseases could lead to its acceptance as an
      independent bio-inflammatory marker.

PMID- 29022054
TI  - Diagnosis and management of 365 ureteric injuries following obstetric and
      gynecologic surgery in resource-limited settings.
AB  - INTRODUCTION: Ureteric injuries are among the most serious complications of
      pelvic surgery. The incidence in low-resource settings is not well documented.
      METHODS: This retrospective review analyzes a cohort of 365 ureteric injuries
      with ureterovaginal fistulas in 353 women following obstetric and gynecologic
      operations in 11 countries in Africa and Asia, all low-resource settings. The
      patients with ureteric injury were stratified into three groups according to the
      initial surgery: (a) obstetric operations, (b) gynecologic operations, and (c)
      vesicovaginal fistula (VVF) repairs. RESULTS: The 365 ureteric injuries in this
      series comprise 246 (67.4%) after obstetric procedures, 65 (17.8%) after
      gynecologic procedures, and 54 (14.8%) after repair of obstetric fistulas.
      Demographic characteristics show clear differences between women with iatrogenic
      injuries and women with obstetric fistulas. The study describes abdominal ureter
      reimplantation and other treatment procedures. Overall surgical results were
      good: 92.9% of women were cured (326/351), 5.4% were healed with some residual
      incontinence (19/351), and six failed (1.7%). CONCLUSIONS: Ureteric injuries
      after obstetric and gynecologic operations are not uncommon. Unlike in high
      resource contexts, in low-resource settings obstetric procedures are most often
      associated with urogenital fistula. Despite resource limitations, diagnosis and
      treatment of ureteric injuries is possible, with good success rates. Training
      must emphasize optimal surgical techniques and different approaches to assisted
      vaginal delivery.

PMID- 29022055
TI  - Illness Perceptions are Associated with Quality of Life in Patients with Fibrous
      Dysplasia.
AB  - Fibrous dysplasia (FD) is a rare bone disorder in which normal bone is replaced
      by fibrous tissue resulting in pain, deformities, pathological fractures or
      asymptomatic disease. Illness perceptions are patients' cognitions and emotions
      about their illness and its treatment, which may impact on Quality of Life (QoL).
      Here, we explore illness perceptions in patients with FD compared to other
      disorders, identify factors associated with illness perceptions and evaluate
      their relationship with QoL. Ninety-seven out of 138 eligible patients from the
      LUMC FD cohort completed the Illness Perception Questionnaire-Revised (IPQ-R) and
      the Short Form-36 (SF-36). Age, Gender, Skeletal Burden Score (SBS), FGF-23
      levels, type of FD and SF-36 scores were analysed for an association with illness
      perceptions. We observed significant (p < 0.01) differences in patients' illness
      perceptions between FD subtypes in the domains: identity, timeline acute/chronic
      and consequences. Patients with craniofacial FD reported to perceive more
      consequences (p = 0.022). High SBS was associated with perceiving more negative
      consequences and attributing the cause of FD to psychological factors (p < 0.01),
      and high FGF-23 levels with attributing more symptoms to the disease and
      perceiving more consequences (p < 0.01). The IPQ-R domain identity, timeline
      acute/chronic, timeline cyclical, consequences, emotional representations and
      treatment control were significantly associated with impairments in QoL. Illness
      perceptions in patients with FD relate to QoL, differ from those in patients with
      other disorders, and are associated with disease severity. Identifying and
      addressing maladaptive illness perceptions may improve quality of life in
      patients with FD.

PMID- 29022056
TI  - Implant strategy affects scaffold stability and integrity in cartilage treatment.
AB  - PURPOSE: To identify the most appropriate implantation strategy for a novel
      chondral scaffold in a model simulating the early post-operative phase, in order
      to optimize the implant procedure and reduce the risk of early failure. METHODS:
      Eight human cadaveric limbs were strapped to a continuous passive motion device
      and exposed to extension-flexion cycles (0 degrees -90 degrees ). Chondral
      lesions (1.8 cm diameter) were prepared on condyles, patella and trochlea for the
      implant of a bi-layer collagen-hydroxyapatite scaffold. The first set-up compared
      four fixation techniques: press-fit (PF) vs. fibrin glue (FG) vs. pins vs.
      sutures; the second compared circular and square implants; the third investigated
      stability in a weight-bearing simulation. The scaffolds were evaluated using semi
      quantitative Drobnic and modified Bekkers scores. RESULTS: FG presented higher
      total Drobnic and Bekkers scores compared to PF (both p = 0.002), pins (p = 0.013
      and 0.001) and sutures (p = 0.001 and < 0.0005). Pins offered better total
      Drobnic and Bekkers scores than PF in the anterior femoral condyles (p = 0.007
      and 0.065), similar to FG. The comparison of round and square implants applied by
      FG showed worst results for square lesions (Drobnic score p = 0.049, Bekkers
      score p = 0.037). Finally, load caused worst overall results (Drobnic p = 0.018).
      CONCLUSIONS: FG improves the fixation of this collagen-HA scaffold regardless of
      lesion location, improving implant stability while preserving its integrity. Pins
      represent a suitable option only for lesions of the anterior condyles. Square
      scaffolds present weak corners, therefore, round implants should be preferred.
      Finally, partial weight-bearing simulation significantly affected the scaffold.
      These findings may be useful to improve surgical technique and post-operative
      management of patients, to optimize the outcome of chondral scaffold
      implantation.

PMID- 29022057
TI  - Multiple cannulated screws vs. dynamic hip screws for femoral neck fractures : A
      meta-analysis.
AB  - OBJECTIVE: Various fixation devices have been reported for stabilization of
      femoral neck fractures. Numerous studies on arthroplasty versus internal fixation
      devices in the treatment of femoral neck fractures have been performed, but the
      optimal approach for internal fixation has not been analyzed. METHODS: A meta
      analysis and system evaluation were performed to compare clinical effects. We
      searched PubMed, Embase, Cochrane Library, and Web of ScienceTM for randomized,
      controlled trials (RCTs) comparing multiple cannulated screws (MCS) with dynamic
      hip screws (DHS) and analyzed the failure rate of operations, the reoperation
      rate, and postoperative complications. Risk ratios (RRs) and mean differences
      from each trial were pooled using random effects or fixed effects models,
      depending on study heterogeneity. The analysis was performed using RevMan5.2.
      RESULTS: In this meta-analysis, 592 femoral neck fractures from 7 studies were
      assessed, and the meta-analysis results indicated significant differences in
      reoperation (RR 1.44, 95% confidence interval [CI] 1.10-1.88, P = 0.008) and
      failure rate (RR 2.28, 95% CI 1.10-4.72, P = 0.03), but no significant
      differences in the rate of postoperative complications between the MCS group and
      DHS group. CONCLUSIONS: DHS fixation has a larger skin incision and more soft
      tissue dissection, but it is associated with lower rates of fixation failure,
      reoperation, and overall rate of postoperative complications, and its use in
      elderly patients with osteoporosis is still recommended due to simplicity,
      efficacy, and high overall success rate. Multicenter RCTs with large samples are
      needed to better understand the comparative efficacy and safety of MCS and DHS in
      femoral neck fractures of restricted fracture type.

PMID- 29022058
TI  - [PSMA-radioguided surgery in localised recurrent prostate cancer].
AB  - Recently, prostate-specific membrane antigen radioguided surgery (PSMA-RGS) was
      introduced for targeted resection of localised prostate cancer recurrence.
      Preliminary results show that PSMA-RGS is very sensitive and specific in tracking
      suspicious lesions intraoperatively. Prerequisite for PSMA-RGS is a positive 68Ga
      PSMA positron emission tomography (PET) scan with a preferably singular soft
      tissue or lymph node recurrence. The first 63 patients treated with PSMA-RGS were
      analyzed. The extracorporal analysis of a total of 277 tissue specimens yielded
      the following test quality criteria regarding the presence of malignant tissue:
      sensitivity 86.2%, specificity 96.4%, positive predictive value 94%, negative
      predictive value 91.5%. Oncological follow-up data was available from 59
      patients. There was a drop in PSA (prostate specific antigen) below 0.2 ng/ml in
      38 patients (67%). Of these 38 patients, 17 (45%) are free of biochemical
      recurrence after a median follow-up of 12.3 months (6.7-31.9 months). Clavien
      Dindo grade III complications occurred in 6 of 63 patients (9.5%). In summary,
      PSMA-RGS proved to be of high value in patients with localised prostate cancer
      recurrence for exact localisation and resection of oftentimes small metastatic
      tissue using intraoperative and ex vivo gamma-probe measurements. Furthermore,
      PSMA-RGS has the potential to positively influence oncological outcomes. However,
      patient identification on the basis of 68Ga-PSMA PET imaging and clinical
      parameters is crucial to obtain satisfactory results.

PMID- 29022060
TI  - [Paresthesia and swollen condition of the tongue].

PMID- 29022059
TI  - Targeted intervention of acute postoperative infection after rotator cuff repair
      results in good functional outcomes.
AB  - PURPOSE: The primary goal of this retrospective review of a prospective database
      was to document the functional results after acute postoperative deep infection
      following rotator cuff repair in a single orthopaedic unit over a period of 5
      years. Secondary goals were to document the effect of infection on healing of the
      cuff repair and to describe its incidence, diagnostic challenges, pathogens and
      management. METHODS: Patients undergoing arthroscopic rotator cuff repair were
      prospectively registered from 2010 to 2014. Eleven out of 1072 repairs developed
      an acute postoperative infection. The patients were examined with an MRI scan,
      Constant-Murley (CM) score and the Western Ontario Rotator Cuff Index (WORC) at
      final follow-up (median of 22 months). RESULTS: All 11 patients who developed
      acute postoperative deep infections were males. Median age was 56 years (range 41
      68). All patients underwent arthroscopic debridement and biopsies were collected
      at a median of 26 days (range 14-50) after primary surgery. In ten patients,
      Propionibacterium acnes was cultured, six of these patients also had positive
      cultures for coagulase-negative staphylococci. In the remaining patient, only
      coagulase-negative staphylococcus was cultured. Five patients were treated with
      one arthroscopic debridement, five had two arthroscopic debridements and one
      required arthroscopic debridement four times before the infection was eradicated.
      Two patients had their implants removed due to loosening of the suture anchors.
      All patients were treated with parenteral antibiotics for 1-4 weeks, followed by
      oral treatment for 1-5 weeks. At median 22 months (range 11-28) follow-up the
      median CM score was 84 and median WORC index was 81%. Ten patients had a
      postoperative MRI scan after a median of 23 months (range 3-49), with eight
      presenting a healed cuff repair. CONCLUSION: The findings of this study support
      the rapid, targeted intervention of acute postoperative infection after RC repair
      with immediate arthroscopic debridement, irrigation and biopsies for
      bacteriological diagnostics followed by parenteral antibiotics. Furthermore,
      repeated arthroscopic debridement and irrigation are recommended if signs of
      infection persist. Removal of the implant is rarely needed. Despite the
      postoperative acute infection, these patients presented good functional results
      at final follow-up. LEVEL OF EVIDENCE: Level III.

PMID- 29022061
TI  - What's new in trace elements?

PMID- 29022063
TI  - Community Structure of Active Aerobic Methanotrophs in Red Mangrove (Kandelia
      obovata) Soils Under Different Frequency of Tides.
AB  - Methanotrophs are important microbial communities in coastal ecosystems. They
      reduce CH4 emission in situ, which is influenced by soil conditions. This study
      aimed to understand the differences in active aerobic methanotrophic communities
      in mangrove forest soils experiencing different inundation frequency, i.e., in
      soils from tidal mangroves, distributed at lower elevations, and from dwarf
      mangroves, distributed at higher elevations. Labeling of pmoA gene of active
      methanotrophs using DNA-based stable isotope probing (DNA-SIP) revealed that
      methanotrophic activity was higher in the dwarf mangrove soils than in the tidal
      mangrove soils, possibly because of the more aerobic soil conditions.
      Methanotrophs affiliated with the cluster deep-sea-5 belonging to type Ib
      methanotrophs were the most dominant methanotrophs in the fresh mangrove soils,
      whereas type II methanotrophs also appeared in the fresh dwarf mangrove soils.
      Furthermore, Methylobacter and Methylosarcina were the most important active
      methanotrophs in the dwarf mangrove soils, whereas Methylomonas and
      Methylosarcina were more active in the tidal mangrove soils. High-throughput
      sequencing of the 16S ribosomal RNA (rRNA) gene also confirmed similar
      differences in methanotrophic communities at the different locations. However,
      several unclassified methanotrophic bacteria were found by 16S rRNA MiSeq
      sequencing in both fresh and incubated mangrove soils, implying that
      methanotrophic communities in mangrove forests may significantly differ from the
      methanotrophic communities documented in previous studies. Overall, this study
      showed the feasibility of 13CH4 DNA-SIP to study the active methanotrophic
      communities in mangrove forest soils and revealed differences in the
      methanotrophic community structure between coastal mangrove forests experiencing
      different tide frequencies.

PMID- 29022062
TI  - FAK tyrosine phosphorylation is regulated by AMPK and controls metabolism in
      human skeletal muscle.
AB  - AIMS/HYPOTHESIS: Insulin-mediated signals and AMP-activated protein kinase (AMPK)
      mediated signals are activated in response to physiological conditions that
      represent energy abundance and shortage, respectively. Focal adhesion kinase
      (FAK) is implicated in insulin signalling and cancer progression in various non
      muscle cell types and plays a regulatory role during skeletal muscle
      differentiation. The role of FAK in skeletal muscle in relation to insulin
      stimulation or AMPK activation is unknown. We examined the effects of insulin or
      AMPK activation on FAK phosphorylation in human skeletal muscle and the direct
      role of FAK on glucose and lipid metabolism. We hypothesised that insulin
      treatment and AMPK activation would have opposing effects on FAK phosphorylation
      and that gene silencing of FAK would alter metabolism. METHODS: Human muscle was
      treated with insulin or the AMPK-activating compound 5-aminoimadazole-4
      carboxamide ribonucleotide (AICAR) to determine FAK phosphorylation and glucose
      transport. Primary human skeletal muscle cells were used to study the effects of
      insulin or AICAR treatment on FAK signalling during serum starvation, as well as
      to determine the metabolic consequences of silencing the FAK gene, PTK2. RESULTS:
      AMPK activation reduced tyrosine phosphorylation of FAK in skeletal muscle. AICAR
      reduced p-FAKY397 in isolated human skeletal muscle and cultured myotubes.
      Insulin stimulation did not alter FAK phosphorylation. Serum starvation increased
      AMPK activation, as demonstrated by increased p-ACCS222, concomitant with reduced
      p-FAKY397. FAK signalling was reduced owing to serum starvation and AICAR
      treatment as demonstrated by reduced p-paxillinY118. Silencing PTK2 in primary
      human skeletal muscle cells increased palmitate oxidation and reduced glycogen
      synthesis. CONCLUSIONS/INTERPRETATION: AMPK regulates FAK signalling in skeletal
      muscle. Moreover, siRNA-mediated FAK knockdown enhances lipid oxidation while
      impairing glycogen synthesis in skeletal muscle. Further exploration of the
      interaction between AMPK and FAK may lead to novel therapeutic strategies for
      diabetes and other chronic conditions associated with an altered metabolic
      homeostasis.

PMID- 29022065
TI  - [Allograft reconstruction in revision elbow arthroplasty].
AB  - BACKGROUND: There is limited knowledge on composite allograft reconstructions in
      revision elbow arthroplasty. A major reason for the restricted use of freshly
      frozen allografts is the divergent legal requirements for allograft procurement
      in European countries. RESULTS: The opportunities and limitations of this complex
      revision surgery of the elbow are outlined based on our own restricted
      experiences, as well as on current literature. Our experience is in accordance
      with that of other institutions. The results are heterogeneous and range from
      satisfying to poor. The main problems are the increased risk of infection and the
      lack of allograft incorporation. Therefore, salvage procedures such as resection
      arthroplasty still need to be considered. It is not possible to define
      universally applicable treatment guidelines due to the limited caseload, even
      when an acceptable functional outcome can be achieved in the majority of cases.
      Due to the lack of a "simple solution" or valid guidelines, treatment strategies
      should be individualized for each patient. Complications such as infection and
      failed allograft incorporation represent the key issues of this procedure and
      remain a major challenge in revision surgery.

PMID- 29022064
TI  - Proinflammatory switch from Galphas to Galphai signaling by Glucagon-like peptide
      1 receptor in murine splenic monocyte following burn injury.
AB  - OBJECTIVE: Glucagon-like peptide-1 (GLP-1)-based therapy via G protein-coupled
      receptor (GPCR) GLP-1R, to attenuate hyperglycemia in critical care has attracted
      great attention. However, the exaggerated inflammation by GLP-1R agonist, Exendin
      4, in a mouse model of burn injury was quite unexpected. Recent studies found
      that GPCR might elicit proinflammatory effects by switching from Galphas to
      Galphai signaling in the immune system. Thus, we aimed to investigate the
      possible Galphas to Galphai switch in GLP-1R signaling in monocyte following burn
      injury. MATERIALS AND METHODS: Splenic monocytes from sham and burn mice 24 h
      following burn injury were treated with consecutive doses of Exendin-4 alone or
      in combination with an inhibitor of Galphai signaling (pertussis toxin, PTX), or
      a blocker of protein kinase A (H89). Cell viability was assessed by CCK-8, and
      the supernatant was collected for cytokine measurement by ELISA. Intracellular
      cAMP level, phosphorylated PKA activity, and nuclear NF-kappaB p65 were
      determined by ELISA, ERK1/2 activation was analyzed by Western blot. The
      expression of GLP-1R downstream molecules, Galphas, Galphai and G-protein coupled
      receptor kinase 2 (GRK2) were examined by immunofluorescence staining and Western
      blot. RESULTS: Exendin-4 could inhibit the viability of monocyte from sham rather
      than burn mice. Unexpectedly, it could also reduce TNF-alpha secretion from sham
      monocyte while increase it from burn monocyte. The increased secretion of TNF
      alpha by Exendin-4 from burn monocyte could be reversed by pretreatment of PTX or
      H89. Accordingly, Exendin-4 could stimulates cAMP production dose dependently
      from sham instead of burn monocyte. However, the blunt cAMP production from burn
      monocyte was further suppressed by pretreatment of PTX or H89 after 6-h
      incubation. Nevertheless, phosphorylated PKA activity was significantly increased
      by low dose of Exendin-4 in sham monocyte, by contrast, it was enhanced by high
      dose of Exendin-4 in burn monocyte after 1-h incubation. Following Exendin-4
      treatment for 2 h ex vivo, total nuclear NF-kappaB and phosphorylated NF-kappaB
      activity, as well as cytoplasmic pERK1/2 expressions were reduced in sham
      monocyte, however, only pERK1/2 was increased by Exendin-4 in burn monocytes.
      Moreover, reduced expressions of GLP-1R, GRK-2 and Galphas in contrast with
      increased expression of Galphai were identified in burn monocyte relative to sham
      monocyte. CONCLUSIONS: This study presents an unexpected proinflammatory switch
      from Galphas to Galphai signaling in burn monocyte, which promotes ERK1/2 and NF
      kappaB activation and the downstream TNF-alpha secretion. This phenomenon is most
      probably responsible for proinflammatory response evoked by Galphas agonist
      Exendin-4 following burn injury.

PMID- 29022067
TI  - Cost-Effective Live Cell Density Determination of Liquid Cultured Microorganisms.
AB  - Live monitoring of microorganisms growth in liquid medium is a desired parameter
      for many research fields. A wildly used approach for determining microbial liquid
      growth quantification is based on light scattering as the result of the physical
      interaction of light with microbial cells. These measurements are generally
      achieved using costly table-top instruments; however, a live, reliable, and
      straight forward instrument constructed using parts that are inexpensive may
      provide opportunities for many researchers. Here, such an instrument has been
      constructed and tested. It consists of modular test tube holding chambers, each
      with a low power monochromatic light-emitting diode, and a monolithic photodiode.
      A microcontroller connects to all modular chambers to control the diodes, and
      send the live data to either an LCD screen, or a computer. This work demonstrate
      that this modular instrument can determine precise cell concentrations for the
      bacteria Escherichia coli and Pseudomonas syringae pv. tomato DC3000, as well as
      Saccharomyces cerevisiae yeast.

PMID- 29022066
TI  - Spirosoma harenae sp. nov., a Bacterium Isolated from a Sandy Beach.
AB  - A Gram-stain-negative, non-motile, non-spore-forming, rod-shaped, aerobic
      bacterium, designated 15J8-9T, was isolated from a sandy beach in Jeju Island,
      South Korea. The isolate was able to grow between 10 and 30  degrees C, pH 5-8,
      and in presence of 0-1% (w/v) NaCl. Based on 16S rRNA gene phylogenetic analysis,
      the novel strain was closely related to members of the genus Spirosoma (96.1
      90.9% similarities) and showed highest sequence similarity to Spirosoma
      panaciterrae DSM 21099T (96.1%). The G + C content of the genomic DNA of strain
      15J8-9T was 45.1 mol%. The isolate contained menaquinone MK-7 as the predominant
      respiratory quinone, phosphatidylethanolamine as the major polar lipid, and
      summed feature 3 (C16:1 omega6c/C16:1 omega7c; 28.0%), C16:1 omega5c (23.4%), iso
      C15:0 (13.5%), and C16:0 (11.5%) as the major fatty acids that supported the
      affiliation of strain 15J8-9T to the genus Spirosoma. The isolate could be
      differentiated clearly from recognized Spirosoma species on the basis of several
      phenotypic, genotypic and chemotaxonomic features. Therefore, strain 15J8-9T is
      considered to represent a novel species of the genus the genus Spirosoma, for
      which the name Spirosoma harenae sp. nov. is proposed. The type strain is 15J8-9T
      (= KCTC 52030T = JCM 31993T).

PMID- 29022069
TI  - Guest editor's introduction: abdominal aorta.

PMID- 29022068
TI  - Esophagectomy for End-Stage Achalasia: Systematic Review and Meta-analysis.
AB  - BACKGROUND: Indications for surgery and clinical outcomes of esophagectomy in the
      management of end-stage achalasia are not clearly defined. The aim of this
      systematic review and meta-analysis was to provide evidence-based information to
      help in the decision-making and in the choice of surgical technique. METHODS: An
      extensive literature search was conducted to identify all reports on
      esophagectomy for end-stage achalasia patients over the past three decades.
      MEDLINE, Embase and Cochrane databases were thoroughly consulted matching the
      terms "achalasia," "end-stage achalasia," "esophagectomy" and "esophageal
      resection" with "AND" and "OR." Short- and long-term outcome data were extracted.
      Pooled prevalence of pneumonia, anastomotic leakage and mortality were calculated
      using Freeman-Tukey double arcsine transformation and DerSimonian-Laird estimator
      in random effect meta-analysis. Heterogeneity among studies was evaluated using I
      2-index and Cochrane Q test. Meta-regression was used to address the effect of
      potential confounders. RESULTS: Eight papers published between 1989 and 2014
      matched the inclusion criteria. In total, 1307 patients were included.
      Esophagectomy was performed through a transthoracic (78.7%) or a transhiatal
      (21.3%) approach. The stomach was used as an esophageal substitute in 95% of
      patients. Pooled prevalence of pneumonia, anastomotic leakage and mortality were
      10% (95% CI 4-18%), 7% (95% CI 4-10%) and 2% (95% CI 1-3%), respectively.
      CONCLUSIONS: Esophagectomy for end-stage achalasia is safe and effective. Based
      on the results of this study, esophagectomy should be performed without
      hesitation in patients who are fit for major surgery and present with disabling
      symptoms, poor quality of life and dolichomegaesophagus recalcitrant to multiple
      endoscopic dilatations and/or surgical myotomies.

PMID- 29022070
TI  - Surgical Resection for Pulmonary Carcinoid: Long-Term Results of Multicentric
      Study-The Importance of Pathological N Status, More Than We Thought.
AB  - BACKGROUND: Histological subdivision into typical (TC) and atypical (AC) is
      crucial for treatment and prognosis of lung carcinoids but can be also very
      challenging, even for experts. In this study, we aimed to strengthen or reduce
      the prognostic value of several pathological, clinical, or per-operative factors
      some of which are still controversial. METHODS: We retrospectively reviewed
      clinical records related to 195 patients affected by TC (159) or AC (36)
      surgically treated between 2000 and 2014, in three different centers. Survival
      and subtypes comparison analyses were performed to identify potential prognostic
      factors. RESULTS: TCs showed a lower rate of nodal involvement than ACs (N0 =
      94.9%; N1 = 1.9%; N2 = 3.2% in typical and N0 = 63.8%; N1 = 16.6%; N2 = 19.4% in
      atypical carcinoids, respectively, p < 0.0001). Long-term oncological results of
      resected carcinoids were significantly better in TCs than ACs with higher 5- and
      10-year overall survival rates (97.2 and 88.2% vs. 77.9 and 68.2%, respectively;
      p = 0.001) and disease-free survival rates (98.2 and 90.3% in typical and 80.8
      and 70.7% atypical carcinoids, respectively; p = 0.001). Risk factors analysis
      revealed that AC subtype [HR 4.33 (95% CI 1.72-8.03), p = 0.002], pathological
      nodal involvement [HR 3.05 (95% CI 1.77-5.26), p < 0.0001], and higher SUVmax [HR
      4.33 (95% CI 1.03-7.18), p = 0.002] were independently and pejoratively
      associated with overall survival. Factors associated with a higher risk of
      recurrence were AC subtype [HR 6.13 (95% CI 1.13-18.86), p = 0.002]; nodal
      involvement [HR 5.48 (95% CI 2.85-10.51), p < 0.0001]; higher Ki67 expression
      level [HR 1.09 (95% CI 1.01-1.20), p = 0.047]; and SUVmax [HR 1.83 (95% CI 1.04
      3.23), p = 0.035]. CONCLUSION: Surgery for lung carcinoids allows satisfactory
      oncological results which mainly depend on carcinoid subtype dichotomy,
      pathological nodal status, and SUVmax.

PMID- 29022071
TI  - Sex differences in tobacco withdrawal and responses to smoking reduced-nicotine
      cigarettes in young smokers.
AB  - RATIONALE: Policies that establish a standard for reduced nicotine content in
      cigarettes can decrease the prevalence of smoking in the USA. Cigarettes with
      nicotine yields as low as 0.05 mg produce substantial occupancy of nicotinic
      acetylcholine receptors (26%), but women and men respond differently to these
      cigarettes. OBJECTIVE: This study aimed to measure responses to smoking
      cigarettes that varied widely in nicotine yields, investigating whether sex
      differences in the effects on craving, withdrawal, and affect would be observed
      at even lower nicotine yields than previously studied, and in young smokers.
      METHODS: Overnight abstinent young smokers (23 men, 23 women, mean age 22.18)
      provided self-reports of craving, withdrawal, and affect before and after smoking
      cigarettes with yields of 0.027, 0.110, 0.231, or 0.763 mg nicotine, and
      evaluated characteristics of each cigarette. RESULTS: Compared to abstinent young
      men, abstinent young women reported greater negative affect, psychological
      withdrawal, and sedation, all of which were relieved equally by all cigarettes.
      Men but not women reported greater craving reduction, perceived nicotine content,
      and cigarette liking with increasing nicotine dose. CONCLUSIONS: Men may
      experience less smoking-related relief of craving, and enjoy cigarettes less, if
      nicotine yields are reduced to very low levels. Conversely, women respond equally
      well to cigarettes with nicotine yields as low as 0.027 mg as to cigarettes with
      nicotine yields 28-fold higher (0.763 mg). These differences are relevant for
      policy regarding reduced nicotine in cigarettes and may influence the efficacy
      and acceptability of reduced-nicotine cigarettes as smoking cessation aids.

PMID- 29022072
TI  - Effect of pathological high-risk features on cancer-specific mortality in non
      metastatic clear cell renal cell carcinoma: a tool for optimizing patient
      selection for adjuvant therapy.
AB  - PURPOSE: Adjuvant therapies for non-metastatic renal cell carcinoma (nmRCC) are
      being tested to improve outcomes in patients with high-risk (hR) nmRCC. The
      objective of the current study is to test the ability of three hR features to
      identify patients who are at the highest risk of cancer-specific mortality (CSM)
      after partial or radical nephrectomy. METHODS: Within the Surveillance
      Epidemiology and End Results (SEER) database (1988-2013), we identified 23,632 nm
      "clear cell" RCC partial or radical nephrectomy patients with hR features:
      Fuhrman grade (FG) 3 or 4 or pathological classifications T3a or T3b or lymph
      node invasion (LNI), or combination of these. Kaplan-Meier analyses (KM) and
      multivariable Cox's regression models (CRM) evaluated the effect of hR features
      on CSM. RESULTS: Overall 11,568 (48.9%) patients harbored FG3-4, 5575 (23.6%)
      pT3a/b, 140 (0.6%) LNI, 5366 (22.7%) FG3-4 and pT3a/b, 183 (0.8%) LNI and pT3a/b,
      203 (0.9%) LNI and FG3-4 and 597 (2.5%) LNI, FG3-4 and pT3a/b. Median CSM-free
      survival was 51, 58 and 22 months for LNI and pT3a/b, for LNI and FG3-4 and for
      LNI, FG3-4 and pT3a/b and was not reached for the other groups. These results
      remained unchanged in multivariable CRMs, where all hR features represented
      independent predictors. CONCLUSIONS: Individuals with combination of LNI with FG3
      4 or pT3a/b and patients with all three hR features are at highest risk of CSM.
      In consequence, these patients may represent ideal candidates for adjuvant
      therapy either in clinical practice or future prospective trials.

PMID- 29022073
TI  - The contribution of cell wall composition in the expansion of Camellia sinensis
      seedlings roots in response to aluminum.
AB  - MAIN CONCLUSION: Treatment with aluminum triggers a unique response in tea
      seedlings resulting in biochemical modification of the cell wall, regulation of
      the activity of the loosening agents, and elongation of root. Unlike most
      terrestrial plants, tea (Camellia sinensis L.) responds to aluminum (Al) through
      the promotion of its root elongation; but the real mechanism(s) behind this
      phenomenon is not well understood. A plausible relationship between the
      modifications of the cell wall and the promotion of root elongation was examined
      in tea seedlings treated for 8 days with 400 uM Al. The mechanical properties of
      the cell wall, the composition of its polysaccharides and their capacity to
      absorb Al, the expression of genes, and the activities of the wall-modifying
      proteins were studied. With 6 h of the treatment, about 40% of the absorbed Al
      was bound to the cell wall; however, the amount did not increase thereafter.
      Meanwhile, the activity of pectin methylesterase, the level of pectin
      demethylation, the amounts and the average molecular mass of xyloglucan in the
      root apices significantly decreased upon exposure to Al, resulting in the
      reduction of Al binding sites. On the other hand, the activity and the gene
      expression of peroxidase decreased, whereas the activity and gene expression of
      xyloglucan-degrading enzymes, the expression of expansin A and the H +-ATPase4
      genes increased in the Al-treated plants. Interestingly, it was accompanied by
      the increase of elastic and viscous extensibility of the root apices. From the
      results, it can be suggested that the biochemical modification of the cell walls
      reduces sites of Al binding to roots and triggers the activity of the loosening
      agents, thereby increasing the length of tea roots.

PMID- 29022075
TI  - A negative answer to a conjecture arising in the study of selection-migration
      models in population genetics.
AB  - We deal with the study of the evolution of the allelic frequencies, at a single
      locus, for a population distributed continuously over a bounded habitat. We
      consider evolution which occurs under the joint action of selection and arbitrary
      migration, that is independent of genotype, in absence of mutation and random
      drift. The focus is on a conjecture, that was raised up in literature of
      population genetics, about the possible uniqueness of polymorphic equilibria,
      which are known as clines, under particular circumstances. We study the number of
      these equilibria, making use of topological tools, and we give a negative answer
      to that question by means of two examples. Indeed, we provide numerical evidence
      of multiplicity of positive solutions for two different Neumann problems
      satisfying the requests of the conjecture.

PMID- 29022074
TI  - Probable psychiatric disorder in a rural community of West Bengal, India.
AB  - PURPOSE: India faces multiple challenges to mitigate a high burden of psychiatric
      disorders. The risk of developing psychiatric disorder among the rural Indian
      population is poorly investigated. This study aims to understand the factors
      associated with probable psychiatric disorder (PPD) among a select rural Indian
      population. METHODS: Data from the Birbhum population project of the society for
      health and demographic surveillance, West Bengal, India, were utilized. Cross
      sectional data covering a sample of 31,135 respondents (male 15,384 and female
      15,751) aged >= 16 years were used. The General Health Questionnaire-28 was
      administered and the responses were computed into three categories: psychological
      case, psychological caseness, and normal. Bivariate and multivariate ordered
      logit regression analyses were applied to attain the study objective. RESULTS: Of
      the total population, 26% of respondents were identified with PPD. People aged >=
      60 years, females, divorced/separated/widowed individuals, the unemployed and
      people with no formal education, individuals from the poorest economic group, and
      people with a history of selling or mortgaging assets towards their healthcare
      expenditure had a higher prevalence of psychiatric case within their respective
      group. CONCLUSIONS: A high burden of PPD was estimated in the select rural
      community. While designing an intervention for measuring and addressing
      psychiatric disorders, the socioeconomic gradient of PPD could be helpful.

PMID- 29022076
TI  - Biosynthesis and regulation of cyanogenic glycoside production in forage plants.
AB  - The natural products cyanogenic glycosides (CNglcs) are present in various forage
      plant species including Sorghum spp., Trifolium spp., and Lotus spp. The release
      of toxic hydrogen cyanide (HCN) from endogenous CNglcs, which is known as
      cyanogenesis, leads to a serious problem for animal consumption while as
      defensive secondary metabolites, CNglcs play multiple roles in plant development
      and responses to adverse environment. Therefore, it is highly important to fully
      uncover the molecular mechanisms of CNglc biosynthesis and regulation to
      manipulate the contents of CNglcs in forage plants for fine-tuning the balance
      between defensive responses and food safety. This review summarizes recent
      studies on the production, function, polymorphism, and regulation of CNglcs in
      forage plants, aiming to provide updated knowledge on the ways to manipulate
      CNglcs for further beneficial economic effects.

PMID- 29022077
TI  - No association between periodontitis and preterm low birth weight: a case-control
      study.
AB  - PURPOSE: This study aimed to investigate the association between periodontitis in
      pregnant women and adverse pregnancy outcomes by heeding confounding risk factors
      for preterm low birth weight infants. METHODS: This study was reported according
      to The Strengthening the Reporting of Observational Studies in Epidemiology
      (STROBE) Statement. A case-control study was conducted. Medical records of all
      pregnant women attending a prenatal care clinic were screened. Those between 21
      and 34 years and gestational age of 28-32 weeks were initially enrolled in the
      study. The exclusion criteria were then applied: diabetes mellitus, genitourinary
      tract infections, or HIV infection; previous multiple gestations; previous
      preterm birth/low birth weight infants; in vitro fertilization procedures;
      placental, cervical/uterine abnormalities; history of infertility; history of
      drug abuse; and any medical conditions that required antibiotics prophylaxis.
      Patients' anthropometric, demographic, and behavioral characteristics were
      collected. The periodontal clinical parameters were obtained from six sites per
      tooth: clinical attachment level, probing pocket depth, dental plaque index, and
      gingival bleeding index. Women were then allocated into two groups: mothers of
      preterm and/or low birth weight newborns (cases) and mothers of full-term and
      normal birth weight newborns (controls). RESULTS: Periodontal clinical parameters
      were analyzed and reported separately for each group, and no significant
      differences were observed (p > 0.05). Logistic regression analysis revealed that
      periodontal clinical parameters were not associated with the adverse pregnancy
      outcomes. CONCLUSION(S): After controlling for confounding factors, our results
      suggest that maternal periodontal disease is not a risk factor associated with
      preterm low birth weight infants.

PMID- 29022078
TI  - Survival benefit of mantle cell lymphoma patients enrolled in clinical trials; a
      joint study from the LYSA group and French cancer registries.
AB  - PURPOSE: Mantle cell lymphoma (MCL) is a rare non-Hodgkin's lymphoma entity with
      a poor prognosis. Therapeutic advances have improved the survival of patients
      enrolled in clinical trials; however, their impact on patients outside clinical
      trials remains unclear. In this work, we compared patient outcome inside and
      outside clinical trials. METHODS: We identified MCL patients recorded in six
      French population-based registries between 2008 and 2012 to perform a comparison
      with patients enrolled in two prospective multicenter MCL clinical trials
      conducted by the LYSA group during the same period. Variables associated with
      inclusion in a clinical trial were identified using a logistic regression. Pohar
      Perme estimator and Nelson et al. flexible parametric model was used to estimate
      net survival probabilities and prognosis factors on excess mortality. RESULTS: A
      total of 312 registry patients were compared to the 372 patients enrolled in LYSA
      clinical trials. Patients included in clinical trials were younger (median age 60
      vs 74, p < 0.001). Age and Ann Arbor stage IV were independently associated with
      enrollment [OR = 0.09 (0.06-0.12) and OR = 1.61 (1.11-2.34), respectively]. The 4
      year net survival was better in clinical trials [79.9% (75.9-84.7) vs 60.3% (53.6
      67.0)]. This result was confirmed in multivariate analysis in patients older than
      65 years with a lower excess mortality rate [0.33 (0.17-0.66)]. CONCLUSIONS: MCL
      included in trials are highly selected patients who are not representative of MCL
      patients who are encountered in everyday practice. With widened inclusion
      criteria, clinical trial patients could be more representative of the general
      population.

PMID- 29022079
TI  - CO2 laser stapedotomy safety: influence of laser energy and time on bone
      conduction hearing levels.
AB  - Total laser energy in CO2 stapedotomy depends on the laser settings and the
      amount of applications. It is unclear if the amount of total laser energy affects
      bone-conduction hearing thresholds and if possible effects are temporary or
      permanent. Alterations of bone-conduction hearing thresholds after single or
      multiple-shot CO2 laser stapedotomy were analyzed between 1 and 3 weeks and 1.5-6
      months after primary (n = 501) or revision surgeries (n = 153) and correlated to
      time, laser energy, frequency, surgical technique, and pathology encountered in
      revision stapedotomy. In both time periods, most patients showed a lower bone
      conduction threshold in the four-tone puretone average (PTA) at frequencies of
      0.5, 1, 2, and 3 kHz that further improved over time. Between 1 and 3 weeks, the
      improvement was significant in subgroups with cumulative energies lower 1 J and
      successful one-shot technique or in revisions without laser application. The
      remaining subgroups with higher total energies showed significant improvements
      between 1.5 and 6 months. At 4 and 8 kHz, significant improvements were found
      during 1.5-6 months after primary and revision surgery independent of the used
      energy. Repeated CO2 laser applications showed no impairment in bone-conduction
      thresholds and can thus be considered as safe. In most patients, significant, yet
      unexplained, improvements in bone-conduction hearing thresholds were noticed in a
      time- and energy-related pattern.

PMID- 29022080
TI  - Urinary potassium to urinary potassium plus sodium ratio can accurately identify
      hypovolemia in nephrotic syndrome: a provisional study.
AB  - : There is evidence pointing to a decrease of the glomerular filtration rate
      (GFR) in a subgroup of nephrotic children, likely secondary to hypovolemia. The
      aim of this study is to validate the use of urinary potassium to the sum of
      potassium plus sodium ratio (UK/UK+UNa) as an indicator of hypovolemia in
      nephrotic syndrome, enabling detection of those patients who will benefit from
      albumin infusion. We prospectively studied 44 nephrotic children and compared
      different parameters to a control group (36 children). Renal perfusion and
      glomerular permeability were assessed by measuring clearance of para
      aminohippurate and inulin. Vaso-active hormones and urinary sodium and potassium
      were also measured. Subjects were grouped into low, normal, and high GFR groups.
      In the low GFR group, significantly lower renal plasma flow (p = 0.01),
      filtration fraction (p = 0.01), and higher UK/UK+UNa (p = 0.03) ratio were noted.
      In addition, non-significant higher plasma renin activity (p = 0.11) and
      aldosteron (p = 0.09) were also seen in the low GFR group. CONCLUSION: A subgroup
      of patients in nephrotic syndrome has a decrease in glomerular filtration,
      apparently related to hypovolemia which likely can be detected by a urinary
      potassium to potassium plus sodium ratio > 0.5-0.6 suggesting benefit of albumin
      infusion in this subgroup. What is Known: * Volume status can be difficult to
      assess based on clinical parameters in nephrotic syndrome, and albumin infusion
      can be associated with development of pulmonary edema and fluid overload in these
      patients. What is New: * Urinary potassium to the sum of urinary potassium plus
      sodium ratio can accurately detect hypovolemia in nephrotic syndrome and thus
      identify those children who would probably respond to albumin infusion.

PMID- 29022082
TI  - [Persistent abdominal complaints after laparoscopic appendectomy].

PMID- 29022081
TI  - Surgical management and outcomes of 12 cases of Wilms tumour with intracardiac
      extension from a single centre.
AB  - PURPOSE: To review demographics, effect of preoperative chemotherapy on tumour
      thrombus, imaging, operative strategy, and outcomes of 12 patients presenting
      with intracardiac extension of Wilms tumour thrombus. METHODS: A retrospective
      audit was undertaken on patients with intracardiac extension of Wilms tumour.
      Patients were identified from the oncology database and information obtained on
      clinical presentation, stage, preoperative treatment, surgical procedures and
      complications, histology, and survival status. Ethics approval was obtained from
      the University of Cape Town Human Research Ethics Committee. RESULTS: From 1984
      to 2016, 337 children with Wilms tumour were treated. Twelve (3.6%) had
      intracardiac extension of tumour thrombus, nine into the right atrium, and three
      into the right ventricle. Ultrasound, computerized tomography, magnetic resonance
      imaging, and echocardiograms were used to assess thrombus level. Patients were
      staged as stage III(8) and IV(4). All patients received preoperative
      chemotherapy. Thrombus retracted from the heart in two cases. One patient died
      preoperatively. Eleven underwent laparotomy, median sternotomy, and
      cardiopulmonary bypass (CPB). Four underwent cavectomy. Five required cavoatrial
      patches. Thrombus extending into the hepatic veins was extracted in five
      patients. There was one intraoperative complication and one perioperative death.
      Thrombus histology showed viable tumour in 9 of 11 patients. Three patients died
      of progressive disease. Seven patients are currently disease free. CONCLUSION: A
      combination of imaging is required to determine thrombus extent, and this
      facilitates surgical planning. Preoperative chemotherapy may cause thrombus
      regression, thus avoiding CPB. CPB offers appropriate conditions for safe tumour
      thrombus excision. Full management in centres with appropriately experienced
      staff and facilities for CPB is recommended.

PMID- 29022085
TI  - Rare pancreatic tumors.
AB  - In this review, we will focus on rare pancreatic tumors. Most of these tumors do
      not have distinct characteristic appearances so the key to diagnosis requires a
      combination of imaging appearance, laboratory data, patient demographics, and
      associated medical syndromes in order to narrow the differential diagnosis.
      Nonetheless, imaging plays a vital role in narrowing the differential and guiding
      management. While there are many variant pathologic entities that cannot be
      encompassed by a single review, we aim to illustrate the imaging appearance of
      less common pancreatic tumors highlighting key distinctive diagnostic
      characteristics and discuss the implications for management. While there is
      overlap in the imaging appearances of many of these entities, for educational
      purposes, lesions will be categorized into solid (hypoenhancing and
      hyperenhancing), cystic lesions, mesenchymal neoplasms, and neoplasms seen in
      younger patients (< 40 years).

PMID- 29022083
TI  - Adolescent cannabinoid exposure effects on natural reward seeking and learning in
      rats.
AB  - RATIONALE: Adolescence is characterized by endocannabinoid (ECB)-dependent
      refinement of neural circuits underlying emotion, learning, and motivation. As a
      result, adolescent cannabinoid receptor stimulation (ACRS) with phytocannabinoids
      or synthetic agonists like "Spice" cause robust and persistent changes in both
      behavior and circuit architecture in rodents, including in reward-related regions
      like medial prefrontal cortex and nucleus accumbens (NAc). OBJECTIVES AND
      METHODS: Here, we examine persistent effects of ACRS with the cannabinoid
      receptor 1/2 specific agonist WIN55-212,2 (WIN; 1.2 mg/kg/day, postnatal day (PD)
      30-43), on natural reward-seeking behaviors and ECB system function in adult male
      Long Evans rats (PD 60+). RESULTS: WIN ACRS increased palatable food intake, and
      altered attribution of incentive salience to food cues in a sign-/goal-tracking
      paradigm. ACRS also blunted hunger-induced sucrose intake, and resulted in
      increased anandamide and oleoylethanolamide levels in NAc after acute food
      restriction not seen in controls. ACRS did not affect food neophobia or locomotor
      response to a novel environment, but did increase preference for exploring a
      novel environment. CONCLUSIONS: These results demonstrate that ACRS causes long
      term increases in natural reward-seeking behaviors and ECB system function that
      persist into adulthood, potentially increasing liability to excessive natural
      reward seeking later in life.

PMID- 29022084
TI  - Exposure-response analyses of trastuzumab emtansine in patients with HER2
      positive advanced breast cancer previously treated with trastuzumab and a taxane.
AB  - PURPOSE: In the phase III EMILIA study, trastuzumab emtansine (T-DM1)
      significantly improved progression-free survival (PFS) and overall survival (OS)
      versus capecitabine plus lapatinib (control) in previously treated human
      epidermal growth factor receptor 2-positive advanced breast cancer. Using EMILIA
      data, we evaluated the T-DM1 exposure-response relationship. METHODS: Exposure
      response relationships were examined with four exposure metrics [model-predicted
      and observed minimum concentration (C min) and area under the concentration-time
      curve from time zero to day 21 of T-DM1 at cycle 1] and multiple efficacy (OS,
      PFS, objective response rate) and safety (grade >= 3 adverse events, grade >= 3
      thrombocytopenia, grade >= 3 hepatotoxicity) endpoints. RESULTS: An apparent
      exposure-response trend was observed between model-predicted exposure metrics and
      efficacy; trends for observed exposure metrics were shallower and often not
      significant. Although median OS and PFS were numerically longer in patients with
      higher versus lower model-predicted cycle 1 C min, OS and PFS hazard ratios for T
      DM1-treated patients in the lowest exposure quartile (Q1) versus control were < 1
      after adjusting for baseline risk factors (e.g., ECOG status, tumor burden,
      measurable disease, and number of disease sites). No meaningful exposure-response
      relationship was observed for any safety endpoints. CONCLUSION: Exposure-response
      relationships for efficacy were inconsistent across exposure metrics; model
      predicted cycle 1 C min showed the strongest exposure-response trend. The Q1
      subgroup based on model-predicted cycle 1 C min had numerically similar or better
      OS and PFS versus control following covariate adjustment. The approved T-DM1 dose
      (3.6 mg/kg every 3 weeks) has a positive benefit-risk ratio versus control, even
      for the T-DM1 Q1 subgroup.

PMID- 29022087
TI  - A comparative analysis of tellurite detoxification by members of the genus
      Shewanella.
AB  - The increasing industrial utilization of tellurium has resulted in an important
      environmental pollution with the soluble, extremely toxic oxyanion tellurite. In
      this context, the use of microorganisms for detoxifying tellurite or tellurium
      biorecovery has gained great interest. The ability of different Shewanella
      strains to reduce tellurite to elemental tellurium was assessed; the results
      showed that the reduction process is dependent on electron transport and the ?pH
      gradient. While S. baltica OS155 showed the highest tellurite resistance, S.
      putrefaciens was the most efficient in reducing tellurite. Moreover, pH-dependent
      tellurite transformation was associated with tellurium precipitation as tellurium
      dioxide. In summary, this work highlights the high tellurite
      reduction/detoxification ability exhibited by a number of Shewanella species,
      which could represent the starting point to develop friendly methods for the
      recovery of elemental tellurium (or tellurium dioxide).

PMID- 29022086
TI  - Lesions Responsible for Delayed Oral Transit Time in Post-stroke Dysphagia.
AB  - INTRODUCTION: Some stroke patients show oral phase dysphagia, characterized by a
      markedly prolonged oral transit time that hinders oral feeding. The aim of this
      study was to clarify the clinical characteristics and lesions responsible for
      delayed swallowing. METHODS: We reviewed 90 patients with stroke. The oral
      processing time plus the postfaucial aggregation time required to swallow
      semisolid food was assessed. The patients were divided into two groups according
      to oral transit time, and we analyzed the differences in characteristics such as
      demographic factors, lesion factors, and cognitive function. Logistic regression
      analyses were performed to examine the predictors of delayed oral transit time.
      Lesion location and volume were measured on brain magnetic resonance images. We
      generated statistic maps of lesions related to delayed oral phase in swallowing
      using voxel-based lesion symptom mapping (VLSM). RESULTS: The group of patients
      who showed delayed oral transit time had significantly low cognitive function.
      Also, in a regression model, delayed oral phase was predicted with low K-MMSE
      (Korean version of the Mini Mental Status Exam). Using VLSM, we found the lesion
      location to be associated with delayed oral phase after adjusting for K-MMSE
      score. Although these results did not reach statistical significance, they showed
      the lesion pattern with predominant distribution in the left frontal lobe.
      CONCLUSION: Delayed oral phase in post-stroke patients was not negligible
      clinically. Patients' cognitive impairments affect the oral transit time. When
      adjusting it, we found a trend that the lesion responsible for delayed oral phase
      was located in the left frontal lobe, though the association did not reach
      significance. The delay might be related to praxis function.

PMID- 29022088
TI  - Enhancement of multiple cranial and spinal nerves in vanishing white matter:
      expanding the differential diagnosis.
AB  - Abnormal cranial or spinal nerve contrast enhancement on MRI in cases of
      suspected pediatric leukodystrophy is recognized as an important clue to the
      diagnosis of either metachromatic leukodystrophy or globoid cell leukodystrophy
      (Krabbe disease). We report a case of genetically confirmed childhood vanishing
      white matter with enhancement of multiple cranial and spinal nerves in addition
      to the more typical intracranial findings. This case expands the limited
      differential diagnosis of cranial nerve or spinal nerve enhancement in cases of
      suspected leukodystrophy and may aid in more efficient work-up and earlier
      diagnosis of vanishing white matter.

PMID- 29022089
TI  - Quantification of altered tissue turnover in a liquid biopsy: a proposed
      precision medicine tool to assess chronic inflammation and desmoplasia associated
      with a pro-cancerous niche and response to immuno-therapeutic anti-tumor
      modalities.
AB  - Immuno-therapy has begun to revolutionize cancer treatment. However, despite the
      significant progress achieved in regard to the duration of clinical benefits, a
      substantial number of patients do not respond to these therapies. To improve the
      outcome of patients receiving immuno-therapy, there is a need for novel
      biomarkers that can predict and monitor treatment. Tumor microenvironment
      alterations, more specifically the state of chronic inflammation and desmoplasia
      (tumor fibrosis), are important factors to consider in this context. Here, we
      discuss the potential for quantification of altered tissue turnover in a liquid
      biopsy as a proposed precision medicine tool to assess chronic inflammation and
      desmoplasia in the immuno-oncology (IO) setting. We highlight the need for novel
      non-invasive biomarkers in IO and the importance of addressing tumor
      microenvironment alterations. We focus on desmoplasia and extracellular matrix
      (ECM) remodeling, and how the composition of the ECM defines T-cell
      permissiveness in the tumor microenvironment and opens up the possibility for
      associated liquid biopsy biomarkers. Moreover, we address the importance of the
      assessment of chronic inflammation, primarily macrophage activity, in a liquid
      biopsy.

PMID- 29022090
TI  - Radiologic evaluation of patients undergoing the modified Appleby procedure for
      locally advanced pancreatic neoplasms: a case series.
AB  - PURPOSE: Despite advances in medical and surgical care, pancreatic ductal
      adenocarcinoma remains one of the most locally aggressive neoplastic processes in
      the abdomen. Unfortunately, most pancreatic adenocarcinomas present late and are
      unresectable at time of diagnosis. The modified Appleby procedure is a surgical
      option in patients with locally advanced pancreatic neoplasms of the body and
      tail with vascular invasion of the celiac trunk. To our knowledge, no radiologic
      journal has previously reported on the pre-operative evaluation or postoperative
      imaging findings of such patients. METHODS: We report herein three patients who
      underwent the modified Appleby procedure, each with a unique complication, in an
      attempt to illustrate common pitfalls of interpretation in these advanced cases.
      RESULTS: Our case series emphasizes the importance of pre-operative radiologic
      assessment of variant arterial anatomy, knowledge of pre- and intraoperative
      procedures and appearances, and familiarity with potential postoperative
      complications. CONCLUSIONS: Thorough understanding of the important aspects of
      the pre-surgical anatomy, as well as possible post-surgical complications, is the
      key to the radiologist being a useful participant in the clinical care of these
      patients.

PMID- 29022091
TI  - Maternal high-fat diet and early life stress differentially modulate spine
      density and dendritic morphology in the medial prefrontal cortex of juvenile and
      adult rats.
AB  - The medial prefrontal cortex (mPFC) is a key area for the regulation of numerous
      brain functions including stress response and cognitive processes. This brain
      area is also particularly affected by adversity during early life. Using an
      animal model in rats, we recently demonstrated that maternal exposure to a high
      fat diet (HFD) prevents maternal separation (MS)-induced gene expression
      alterations in the developing PFC and attenuates several long-term deleterious
      behavioral effects of MS. In the present study, we ask whether maternal HFD could
      protect mPFC neurons of pups exposed to early life stress by examining dendritic
      morphology and spine density in juvenile [postnatal day (PND) 21] and adult rats
      submitted to MS. Dams were fed either a control or an HFD throughout gestation
      and lactation, and pups were submitted to MS from PND2 to PND14. We report that
      maternal HFD prevents MS-induced spine loss at PND21 and dendritic atrophy at
      adulthood. Furthermore, we show in adult MS rats that PFC-dependent memory
      extinction deficits are prevented by maternal HFD. Finally, perinatal HFD
      exposure reverses gut leakiness following stress in pups and seems to exert an
      anti-stress effect in dams. Overall, our work demonstrates that maternal HFD
      affects the developing brain and suggests that nutrition, possibly through gut
      brain interactions, could modulate mPFC sensitivity to early stress.

PMID- 29022092
TI  - Unique manifestations of biliary atresia provide new immunological insight into
      its etiopathogenesis.
AB  - Biliary atresia (BA) is a unique cholestatic disease of newborns with a
      background of exaggerated immune response in the liver of unknown mechanism.
      Three hypotheses have been proposed; autoimmune type of cholangiopathy triggered
      by virus infection, graft-versus-host disease type of immune-mediated disease
      associated with maternal microchimerism and ductal plate malformation theory.
      Researchers on virus infection theory have experimentally explored immune process
      causing cholangiopathy on murine models of this disease, while in maternal
      microchimerism hypothesis were detected maternal cells in the BA patients' liver,
      of which roles are yet to be determined. Ductal plate malformation theory is an
      intriguing hypothesis in the sense that it suggests the onset of this disease is
      in the first trimester. This theory can be secondary to either one of these two
      immune-related insults. In this review, four unique points are focused; (1) the
      timing of onset, (2) hepatitis-like pathological picture, (3) heterogenous
      atrophy of the liver segments when advanced, and (4) swollen lymph nodes at the
      porta hepatis. These unique clinicopahtological aspects of this disease should be
      well explained by these hypotheses.

PMID- 29022093
TI  - [Seasonal allergic conjunctivitis].
AB  - Seasonal allergic conjunctivitis (SAC) is a frequent disease, which is often
      associated with allergic rhinitis and subsequently manifested as allergic
      rhinoconjunctivitis. In contrast to other types of chronic allergic
      conjunctivitis, the course of SAC is not sight-threatening. Pathogenetically, the
      underlying cause of SAC is an immunoglobulin E (IgE) mediated, Th2-driven type 1
      hypersensitivity reaction. Clinically it presents with itching, light-red
      conjunctival injection as well as chemosis that exceeds the extent of
      conjunctival injection. The goals of treatment are relief of acute signs and
      symptoms, control of the underlying inflammatory process and utilization of
      preventive options. Dually effective local therapeutics combine the advantages of
      rapid action with a relatively long-lasting effect by a two-fold active approach.
      Specific immunotherapy is useful in selected patients.

PMID- 29022094
TI  - Transcriptomic changes in Echinochloa colona in response to treatment with the
      herbicide imazamox.
AB  - MAIN CONCLUSION: Presented here is the first Echinochloa colona leaf
      transcriptome. Analysis of gene expression before and after herbicide treatment
      reveals that E. colona mounts a stress response upon exposure to herbicide.
      Herbicides are the most frequently used means of controlling weeds. For many
      herbicides, the target site is known; however, it is considerably less clear how
      plant gene expression changes in response to herbicide exposure. In this study,
      changes in gene expression in response to herbicide exposure in imazamox
      sensitive (S) and- resistant (R) junglerice (Echinochloa colona L.) biotypes was
      examined. As no reference genome is available for this weed, a reference leaf
      transcriptome was generated. Messenger RNA was isolated from imazamox-treated-
      and untreated R and S plants and the resulting cDNA libraries were sequenced on
      an Illumina HiSeq2000. The transcriptome was assembled, annotated, and
      differential gene expression analysis was performed to identify transcripts that
      were upregulated or downregulated in response to herbicide exposure for both
      biotypes. Differentially expressed transcripts included transcription factors,
      protein-modifying enzymes, and enzymes involved in metabolism and signaling. A
      literature search revealed that members of the families represented in this
      analysis were known to be involved in abiotic stress response in other plants,
      suggesting that imazamox exposure induced a stress response. A time course study
      examining a subset of transcripts showed that expression peaked within 4-12 h and
      then returned to untreated levels within 48 h of exposure. Testing of plants from
      two additional biotypes showed a similar change in gene expression 4 h after
      herbicide exposure compared to the resistant and sensitive biotypes. This study
      shows that within 48 h junglerice mounts a stress response to imazamox exposure.

PMID- 29022095
TI  - Laparoscopic portoenterostomy for biliary atresia: single-center experience and
      review of literatures.
AB  - AIM: The aim of this report was to present the laparoscopic portoenterostomy
      (LapPE) procedure developed by the Department of Pediatric General and Urogenital
      Surgery, Juntendo University School of Medicine (JLapPE). We also attempted to
      obtain an understanding of the current status of laparoscopic portoenterostomy in
      the world as reported in the English literature to compare with our experience.
      METHODS: There were 22 BA patients who had JLapPE between 2009 and 2016. BA
      classification was type III (n = 19) and type II (n = 3). There was 1 case of
      syndromic BA and 1 case was positive for cytomegalovirus. A systematic search in
      PubMed of all BA patients treated by LapPE in the English literature was
      conducted. Jaundice clearance (JC) and survival with the native liver (SNL) were
      compared. RESULTS: Mean age at JLapPE was 67.1 days (range 29-119). Mean
      postoperative follow-up was 4.6 years (1.3-8.3). Mean operative time was 514 min
      (240-662) and mean blood loss was 13.4 g (3-21). Postoperative JC (Total
      bilirubin <= 1.5 mg/dL) was 77.3% (17/22) at 3 months and 90.9% (20/22) at 6
      months. SNL at 6 months of age was 90.9% (20/22); at 1 year of age was 77.3%
      (17/22), at 2 years of age was 73.7% (14/19); and at 3 years of age was 81.3%
      (13/16). CONCLUSIONS: Despite recent reports that outcome of LapPE for BA may be
      unfavorable compared with the conventional open portoenterostomy, our results
      would suggest that JLapPE can be performed successfully, because it is performed
      exactingly according to a standard protocol. JLapPE will continue to be our
      procedure of choice for treating BA.

PMID- 29022096
TI  - The association between ambient temperature and childhood asthma: a systematic
      review.
AB  - The objectives of this study are to review available information on the
      association between ambient temperature and childhood asthma, and to elucidate
      the possible underlying mechanisms of this relationship. A systematic review was
      conducted based on the papers retrieved from four databases, including PubMed,
      ProQuest, ScienceDirect, and Scopus. Papers examining the association of absolute
      temperature or temperature variation with childhood asthma published from 1
      January 2000 to 31 December 2016 were included. Thirteen papers have quantified
      the effect of absolute temperature on childhood asthma, and six papers have
      examined the effect of intra- or inter-day temperature variation on childhood
      asthma. All studies were conducted in urban areas. Aeroallergen sensitizations
      were only considered in the analyses of one study. Discrepancy existed in the
      significance of the relationship between absolute temperature and childhood
      asthma, and also in the shape of this relationship (i.e. linear or non-linear)
      and whether temperature effects were lagged. Increasing evidence is suggesting
      non-linear relationship between absolute temperature and childhood asthma. Future
      research should investigate the burden of childhood asthma specifically
      attributable to extreme temperatures and temperature variation using advanced
      statistical approach, particularly in rural areas, after properly considering
      aeroallergens and air pollution. Projecting future burden of childhood asthma
      under climate change scenarios is also warranted.

PMID- 29022098
TI  - [Urinary incontinence 2017 : Current position].

PMID- 29022097
TI  - Prevalence of fibroblast growth factor receptor 1 (FGFR1) amplification in
      squamous cell carcinomas of the head and neck.
AB  - BACKGROUND: FGFR1 is a receptor tyrosine kinases involved in tumor growth
      signaling, survival, and differentiation in many solid cancer types. There is
      growing evidence that FGFR1 amplification might predict therapy response to FGFR1
      inhibitors in squamous cell lung cancers. To estimate the potential applicability
      of anti FGFR1 therapies in squamous cell carcinomas of the head and neck, we
      studied patterns of FGFR1 amplification using fluorescence in situ hybridization
      (FISH). MATERIALS AND METHODS: A tissue microarray was constructed from 453
      primary treatment-naive squamous cell carcinomas of the head and neck regions
      with histopathological and clinical follow-up data [including oral cavity (n =
      222), oropharynx (n = 126), and larynx (n = 105)]. FGFR1 and centromere 8 copy
      numbers were assessed by dual-color FISH. FGFR1 amplification was defined as a
      copy number ratio FGFR1: centromere 8 >= 2.0. HPV sequencing and p16
      immunohistochemistry (IHC) were applied to FGFR1-amplified cancers. RESULTS: FISH
      analysis was successful in 297 (66%) of the 453 cancers. FGFR1 amplification was
      found in 6% of analyzable tumors, and was more frequent in tumors of the oral
      cavity (13/133 amplified, 10%), than cancers of other localizations (1/79
      oropharynx, 4/85 larynx; p = 0.007 and 0.159, respectively). One out of 18 FGFR1
      amplified cancers was HPV positive. No associations were found between FGFR1
      amplification and tumor phenotype or p16 IHC. CONCLUSIONS: Head and neck cancers
      are recurrently affected by FGFR1 amplification, with a predominance in cancers
      of the oral cavity. Finding only one HPV positive and FGFR1 amplified cancer
      argues against a causal relationship between HPV and FGFR1 amplifications.

PMID- 29022099
TI  - Defibrotide for the treatment of sinusoidal obstruction syndrome: evaluation of
      response to therapy and patient outcomes.
AB  - PURPOSE: Defibrotide is an agent used to treat sinusoidal obstruction syndrome
      (SOS/VOD) in patients undergoing haemopoietic stem cell transplantation. The aim
      of this study was to evaluate the effectiveness of defibrotide used within
      institutional guidelines for the treatment of SOS/VOD in patients undergoing
      haemopoietic stem cell transplantation (HSCT). METHODS: Data for 23 patients was
      retrospectively reviewed to evaluate the effectiveness of defibrotide and the
      utility of response criteria to direct therapy as specified within institution
      guidelines. Patients met institutional criteria for a diagnosis of SOS/VOD based
      on predominantly Baltimore criteria and received defibrotide. Stabilisation or
      improvement in symptoms and biochemical markers was required for continuation of
      therapy with defibrotide. RESULTS: Overall, 14 patients responded to therapy.
      Survival at day 100 post HSCT was 70%. Median serum (total) bilirubin
      concentrations in all evaluable patients had decreased at days 5 and 10 (p <
      0.001). There was a proportional reduction in median weight of 4% by day 5 and
      6.6% by day 10 (p < 0.001). On cessation of defibrotide, there was a decrease in
      the proportion of patients exhibiting hepatomegaly (p = 0.02), ascites (p < 0.01)
      and requiring oxygen supplementation (p < 0.01), with 70% survival at day 100
      post HSCT. CONCLUSION: Defibrotide to treat SOS/VOD and continued based on
      attainment of early response was effective management of this condition.
      Defibrotide should be considered in any consensus protocol providing guidance on
      the management of SOS/VOD, with future studies considered to assess appropriate
      time points for response to therapy during treatment.

PMID- 29022100
TI  - Sea buckthorn decreases and delays insulin response and improves glycaemic
      profile following a sucrose-containing berry meal: a randomised, controlled,
      crossover study of Danish sea buckthorn and strawberries in overweight and obese
      male subjects.
AB  - PURPOSE: Berries and mixed berry products exert acute effects on postprandial
      glycaemia and insulinemia, but very few berries have been studied, and primarily
      in normal weight subjects. Sea buckthorn and strawberry are compositionally
      widely different berries and may likely produce different responses. The effects
      of strawberry and sea buckthorn on postprandial glycaemia and insulinemia were
      examined in overweight or obese male subjects. Subjective appetite sensations and
      ad libitum intake were also examined. METHODS: The study was conducted as a
      randomised, controlled, single-blinded, three-way crossover study. Eighteen
      subjects were studied in three 2-h meal tests followed by a subsequent ad libitum
      meal. Test meals contained added sucrose and either sea buckthorn, strawberry or
      no berries with added fructose (control). Blood samples were collected at t = 0,
      30, 45, 60, 90 and 120 min. Subjective appetite sensations were recorded at t =
      0, 15, 30, 45, 60, 90, 120, and 140 min and subsequent ad libitum intake was
      recorded. Statistical differences in all continuous measures were evaluated based
      on the existence of a meal or a time-meal interaction by repeated measures linear
      model analyses or by differences in AUC by linear mixed models. RESULTS: None of
      the berries affected postprandial glucose. However, sea buckthorn improved
      glycaemic profile (44.7%, p < 0.01) compared to control. Sea buckthorn also
      resulted in a decrease in plasma insulin concentration at 30 min (39.6%, p <
      0.01) and at 45 min (16.5%, p < 0.05) compared to control and the maximal
      increase in plasma insulin was lower following sea buckthorn compared with
      control (23.6%, p < 0.01). Strawberry did not affect postprandial insulin
      concentrations compared to control. No differences between control and each of
      the two berries were observed for any of the appetite parameters, except for
      desire for something sweet, which was increased following the sea buckthorn meal
      compared to control. CONCLUSIONS: There was no effect on postprandial glucose
      response to a sugar challenge given together with purees of strawberry or sea
      buckthorn. Sea buckthorn decreased and delayed the insulin response and improved
      glycaemic profile compared with control. Strawberry had no such effects. No
      important differences were seen for the appetite measures. Sea buckthorn might be
      useful as a culinary tool for lowering meal insulin response.

PMID- 29022101
TI  - Microflow imaging: New Doppler technology to detect low-grade inflammation in
      patients with arthritis.
AB  - AIM: To assess the efficacy of microvascular imaging in detecting low-grade
      inflammation in arthritis compared with Power Doppler ultrasound (PDUS). METHOD
      AND MATERIALS: Patients presenting for ultrasound with arthralgia were assessed
      with grey-scale, PDUS and Superb Microvascular Imaging (SMI). Videoclips were
      stored for analysis at a later date. Three musculoskeletal radiologists scored
      grey-scale changes, signal on PDUS and/or SMI within these joints. If a signal
      was detected on both PDUS and SMI, the readers graded the conspicuity of vascular
      signal from the two Doppler techniques using a visual analogue scale. RESULTS:
      Eighty-three patients were recruited with 134 small joints assessed. Eighty-nine
      of these demonstrated vascular flow with both PD and SMI, whilst in five no flow
      was detected. In 40 joints, vascularity was detected with SMI but not with PDUS
      (p = 0.007). Out of the 89 joints with vascularity on both SMI and PDUS, 23 were
      rated as being equal; while SMI scored moderately or markedly better in 45 cases
      (p <0.001). CONCLUSION: SMI is a new Doppler technique that increases conspicuity
      of Doppler vascularity in symptomatic joints when compared to PDUS. This allows
      detection of low grade inflammation not visualised with Power Doppler in patients
      with arthritis. KEY POINTS: * SMI detects vascularity with improved resolution
      and sensitivity compared to Power Doppler. * SMI can detect low-grade
      inflammation not seen with Power Doppler. * Earlier detection of active
      inflammation could have significant impact on treatment paradigms.

PMID- 29022102
TI  - As if the disease was not enough: coping with the financial consequences of
      cancer.
AB  - PURPOSE: The goal of this research was to understand how cancer survivors cope
      with the financial consequences of their disease. METHODS: Twenty-six cancer
      survivors who self-identified as having experienced financial hardship related to
      their disease were interviewed. Transcripts of these interviews were analyzed
      using constructivist grounded theory approach. An analysis of codes related to
      coping strategies was conducted, and findings were stratified based on
      established coping theories (Lazarus and Folkman and Moos and Holahan) previously
      applied to coping with serious/chronic illnesses. RESULTS: Participants used both
      person-oriented/emotion-focused and task/problem-focused coping skills to
      confront the financial consequences of their disease trajectory. Problem-focused
      skills included dealing with debt, accessing financial assistance, making
      lifestyle changes, seeking information and education, altering treatment
      protocols, being proactive, and negotiating insurance. Emotion-focused tasks
      included using personal strengths, expressing emotion, accessing social support,
      being determined, and taking care of oneself. Results were further analyzed using
      Moos and Holahan's framework of coping skills; examples of each of these coping
      skills were identified in the interview data. CONCLUSIONS: Facing serious
      financial ramifications due to a cancer diagnosis calls forth coping skills and
      tasks that can be categorized using coping theories traditionally applied to
      coping with the illness itself. Cancer patients are often confronted with dual
      threats: the physical and emotional impact of the illness and the loss of
      financial security and the lifestyle that they have worked to maintain.
      Interventions with cancer survivors should include facilitating effective coping
      with the financial implications of the disease.

PMID- 29022104
TI  - Deriving and understanding the risk of post-transplant recurrence of nephrotic
      syndrome in the light of current molecular and genetic advances.
AB  - After renal transplantation, recurrence of the original disease is the second
      most common cause of graft loss, after rejection. The most dramatic manifestation
      of this phenomenon is in patients with nephrotic syndrome (NS). NS is a
      descriptive term describing a clinical picture centred on proteinuria arising
      from damage to the glomerular filtration barrier (GFB). There are many different
      drivers of that damage, ranging from immune dysregulation to genetic disorders
      and chronic disease/infections. The main categories in childhood are "idiopathic"
      (presumed immune mediated) and genetic NS, with further stratification of the
      idiopathic group according to steroid responses. A significant proportion of
      patients with NS progress to established renal failure, requiring
      transplantation, and one of the most difficult clinical scenarios faced by
      nephrologists is the recurrence of the original disease in up to 50% of patients,
      usually rapidly post-transplant. This is thought to be the archetypal
      "circulating factor" disease, in which as yet unknown circulating plasma
      "factor(s)" in the recipient target the donor kidney. The ability to predict in
      advance which patients will suffer recurrence would enhance our ability to
      counsel patients and families, and potentially identify those patients before
      transplant for tailored immunosuppressive preparation. Until very recently,
      stratification based on clinical categorisations has been poor in being able to
      predict those patients in whom disease will recur, and laboratory biomarkers are
      yet to be adequately refined. However, by mapping our growing understanding of
      disease mechanisms to clinical phenotypes, and with greatly improved genetic
      diagnostics, we have made progress in being able to stratify patients more
      specifically, and allow better predictive algorithms to be developed. Using our
      knowledge of podocyte biology, circulating factor-induced specific biomarkers are
      also being tested. This review is aimed at outlining those advances, and
      suggesting how we can move further forward in both clinical and biological
      markers of disease type.

PMID- 29022105
TI  - Structural and electronic study of iron-based dye sensitizers for solar cells
      using DFT/TDDFT.
AB  - Ruthenium-based molecules have proven their efficiency as photosensitizers in dye
      sensitized solar cells. However, due to the high cost and scarcity of this noble
      metal, in this work we investigated the effects of replacing the ruthenium in
      photosensitizers with iron because it is less expensive and more abundant. DFT
      and TD-DFT methods were used to explore the resulting systems. The B3LYP
      functional was employed to compute the ground-state geometries and the frontier
      molecular orbitals for four complexes of general formula M(Rbpy)2S2N2C2 (M = Ru
      or Fe; R = COOH or COOEt). We also used TD-M06 to investigate the electronic
      properties and to simulate the absorption spectra of these Ru-based and Fe-based
      complexes. Finally, CPCM was applied to explore the effect of DMF solvent. The
      HOMOs of these Ru-based and Fe-based molecules were found to have metal d orbital
      and pi(S2C2N2) orbital character, while their LUMOs had pi*(R-bpy) orbital
      character. In addition, values of the light-harvesting efficiency (LHE), open
      circuit voltage (V oc), and driving force (?G inject) were calculated for the Ru
      based and Fe-based molecules. According to our results, the maximum absorbance,
      the LHE, V oc, and ?G inject values for complexes 2 and 4 (Fe-based dyes) are
      very close to those of complexes 1 and 3 (Ru-based dyes). Thus, our studies
      indicate that the Ru in photosensitizers can be replaced with the much less
      expensive metal Fe, as the resulting Fe-based dyes appear to be promising
      candidates for use in solar cells.

PMID- 29022106
TI  - Minimally Invasive Adrenalectomy for Adrenocortical Carcinoma: Five-Year Trends
      and Predictors of Conversion.
AB  - BACKGROUND: Adrenocortical carcinoma (ACC) is rare but often fatal. Surgery
      offers the only chance of cure. As minimally invasive (MI) procedures for cancer
      become common, their role for ACC is still debated. We reviewed usage of MI
      approaches for ACC over time and risk factors for conversion using a large
      national database. METHODS: ACC patients with localized disease were identified
      in the National Cancer Data Base from 2010 to 2014. A retrospective review
      examined trends in the surgical approach over time. Patient demographics,
      surgical approach, and tumor characteristics between MI, open, and converted
      procedures were compared. RESULTS: 588 patients underwent adrenalectomy for ACC,
      of which 200 were minimally invasive. From 2010 to 2014, MI operations increased
      from 26 to 44% with robotic procedures increasing from 5 to 16%. The use of MI
      operations compared to open was not different based on facility type (p = 0.40)
      or location (p = 0.63). MI tumors were more likely to be confined to the adrenal
      (p < 0.001) but final margin status was not different (p = 0.56). Conversion was
      performed in 38/200 (19%). Average tumor size was 10.2 cm in the converted group
      compared to 8.6 cm in the MI group (p = 0.09). There was no difference in extent
      of disease (p = 0.33), margin status (p = 0.12), or lymphovascular invasion (p =
      0.59) between MI and converted procedures. Tumor size > 5 cm was the only
      significant predictor of conversion (p = 0.04). No patients with pathologic stage
      I disease required conversion (0/19). CONCLUSIONS: The frequency of MI approaches
      for ACC is increasing. In the final year of the study, 44% of adrenalectomies
      were MI. Size > 5 cm was the only significant predictor of conversion.

PMID- 29022103
TI  - Antidiabetic plant-derived nutraceuticals: a critical review.
AB  - Diabetes mellitus (DM) is one of the major health problems in the world,
      especially amongst the urban population. Chemically synthesized drugs used to
      decrease the ill effects of DM and its secondary complications cause adverse side
      effects, viz., weight gain, gastrointestinal disturbances, and heart failure.
      Currently, various other approaches, viz., diet control, physical exercise and
      use of antidiabetic plant-derived molecules/foods are advocated to manage DM, as
      they are economical with fewer or no side effects. This review mainly focuses on
      antidiabetic plants, chemically characterized plant molecules and plant-based
      foods in the treatment of DM. Very little science-based evidence is available on
      the mechanism of action of plant-derived food molecules on the DM targets.
      Critical DM targets include alpha-amylase, alpha-glucosidase, DPP-IV, aldose
      reductase, PPAR-gamma, AMP kinase and GLUT4. In-depth studies carried out on a
      few of those targets with specific mechanisms of action are addressed in this
      review. This review may help future researchers in identifying a right plant
      molecule to treat DM or to develop food formulations for DM management.

PMID- 29022107
TI  - Preoperative laryngotracheobronchoscopy in infants with esophageal atresia: why
      is it not routine?
AB  - The value of laryngotracheobronchoscopy (LTB) immediately prior to repair of
      esophageal atresia with or without tracheo-esophageal fistula is contentious.
      Currently, there is a wide range of opinion on the utility of this investigation
      which is reflected by huge variation in clinical practice. This review is a
      critical analysis of the arguments for and against performing routine LTB prior
      to esophageal atresia repair. Reserving LTB for selected cases only is
      potentially disadvantageous since it limits the surgeon's and anesthetist's
      familiarity with the procedure, equipment, and range of potential findings. There
      is sufficient evidence to suggest that routine preoperative LTB becomes the
      standard of care.

PMID- 29022108
TI  - Middle cranial fossa approach for the repair of superior semicircular canal
      dehiscence is associated with greater symptom resolution compared to transmastoid
      approach.
AB  - BACKGROUND: Superior semicircular canal dehiscence (SSCD) is a disorder of the
      skull base that is gaining increasing recognition among neurosurgeons.
      Traditionally, the middle cranial fossa (MCF) approach has been used for the
      surgical repair of SSCD. However, the transmastoid (TM) approach is an
      alternative strategy that has demonstrated promising results. METHODS: We
      performed independent searches of a popular database to identify studies that
      described outcomes following the surgical repair of SSCD through MCF and TM
      approaches. The primary outcome was symptom resolution. RESULTS: Our analysis
      included 24 studies that described 230 patients that underwent either an MCF (n =
      148, 64%) approach or a TM (n = 82, 36%) approach for primary surgical repair of
      SSCD. A greater percentage of patients in the MCF group experienced resolution of
      auditory symptoms (72% vs 59%, p = 0.012), aural fullness (83% vs 55%, p =
      0.049), hearing loss (57% vs 31%, p = 0.026), and disequilibrium (75% vs 44%, p =
      0.001) when compared to the TM group. The MCF approach was also associated with
      higher odds of symptom resolution for auditory symptoms (odds ratio [OR] 1.79,
      95% confidence interval [CI] 1.14-2.82), aural fullness (OR 4.02, 95% CI 1.04
      15.53), hearing loss (OR 2.91, 95% CI 1.14-7.42), and disequilibrium (OR 3.94,
      95% CI 1.78-8.73). The mean follow-up was 9 months. CONCLUSIONS: The literature
      suggests that the MCF approach for the repair of SSCD is associated with greater
      symptom resolution when compared to the TM approach. This information could help
      facilitate patient discussions.

PMID- 29022110
TI  - Monitoring Bone Tissue Engineered (BTE) Constructs Based on the Shifting
      Metabolism of Differentiating Stem Cells.
AB  - Ever-increasing demand for bone grafts necessitates the realization of clinical
      implementation of bone tissue engineered constructs. The predominant hurdle to
      implementation remains to be securing FDA approval, based on the lack of viable
      methods for the rigorous monitoring of said constructs. The study presented
      herein details a method for such monitoring based on the shifting metabolism of
      mesenchymal stem cells (MSCs) as they differentiate into osteoblasts. To that
      end, rat MSCs seeded on 85% porous spunbonded poly(L-lactic acid) scaffolds were
      cultured in flow perfusion bioreactors with baseline or osteoinductive media, and
      levels of key physio-metabolic markers (oxygen, glucose, osteoprotegerin, and
      osteocalcin) were monitored throughout culture. Comparison of these non
      destructively obtained values and current standard destructive analyses
      demonstrated key trends useful for the concurrent real-time monitoring of
      construct cellularity and maturation. Principle among these is the elucidation of
      the ratio of the rates of oxygen uptake to glucose consumption as a powerful
      quality marker. This ratio, supported on a physiological basis, has been shown
      herein to be reliable in the determination of both construct maturation (defined
      as osteoblastic differentiation and accompanying mineralization) and construct
      cellularity. Supplementary monitoring of OPG and OCN are shown to provide further
      validation of such metrics.

PMID- 29022111
TI  - A novel strain of porcine deltacoronavirus in Vietnam.
AB  - Two porcine deltacoronavirus (PDCoV) strains (Binh21 and HaNoi6) were isolated
      from two pig farms in North Vietnam. Phylogenetic analysis of the complete
      genomes and the Spike and Membrane genes revealed that the two Vietnam PDCoVs
      belong to the same lineage as PDCoVs from Thailand and Laos; however, the N genes
      belonged to the same lineage as PDCoVs from the USA, Korea, China, and Hong Kong.
      The recombination detection program subsequently identified the major parent
      (S5011 strain) and minor parent (HKU15-44 strain) of the two Vietnam PDCoV
      strains (p < 0.01).

PMID- 29022109
TI  - Interaction of CD80 with Neph1: a potential mechanism of podocyte injury.
AB  - BACKGROUND: The induction of CD80 on podocytes has been shown in animal models of
      podocyte injury and in certain cases of nephrotic syndrome. In a
      lipopolysaccharide (LPS)-induced mouse model of albuminuria, we have recently
      shown a signalling axis of LPS-myeloid cell activation-TNFalpha production
      podocyte CD80 induction-albuminuria. Therefore, in this report, we investigated
      the cellular and molecular consequences of TNFalpha addition and CD80 expression
      on cultured podocytes. METHODS: A murine podocyte cell line was used for TNFalpha
      treatment and for over-expressing CD80. Expression and localization of various
      podocyte proteins was analysed by reverse transcriptase-polymerase chain
      reaction, western blotting and immunofluorescence. HEK293 cells were used to
      biochemically characterize interactions. RESULTS: Podocytes treated with LPS in
      vitro did not cause CD80 upregulation but TNFalpha treatment was associated with
      an increase in CD80 levels, actin derangement and poor wound healing. Podocytes
      stably expressing CD80 showed actin derangement and co-localization with Neph1.
      CD80 and Neph1 interaction was confirmed by pull down assays of CD80 and Neph1
      transfected in HEK293 cells. CONCLUSION: Addition of TNFalpha to podocytes causes
      CD80 upregulation, actin reorganization and podocyte injury. Overexpressed CD80
      and Neph1 interact via their extracellular domain. This interaction implies a
      mechanism of slit diaphragm disruption and possible use of small molecules that
      disrupt CD80-Neph1 interaction as a potential for treatment of nephrotic syndrome
      associated with CD80 upregulation.

PMID- 29022112
TI  - The use of zonal analysis of peripapillary choroidal thickness in primary open
      angle glaucoma.
AB  - PURPOSE: To evaluate automatic peripapillary choroidal thickness (PPCT)
      measurements in a wide area around the optic disc and various established zones
      in primary open-angle glaucoma (POAG) patients and age- and sex-matched healthy
      controls using a new swept-source optical coherence tomography (SS-OCT) device.
      STUDY DESIGN: Single center cross-sectional observational study. METHODS: A total
      of 135 POAG patients and 86 healthy subjects were consecutively enrolled. An
      optic disc 6.0 * 6.0 mm three-dimensional scan OD was obtained using the SS-OCT
      Triton. A 26 * 26 cube-grid centered in the optic disc was generated to
      automatically measure choroidal thickness. Seven choroidal zones were established
      (superior temporal, central, and nasal; inferior temporal, central, and nasal,
      and the optic nerve head) and compared between healthy controls and POAG
      patients. RESULTS: PPCT was significantly thinner in the central superior, nasal
      superior, and nasal inferior zones of the POAG subjects. Choroidal thickness in
      the central superior zone was 124.61 +/- 54.95 um in POAG group vs 156.17 +/-
      80.89 um in healthy controls (p = 0.029); in the nasal superior zone, 133.84 +/-
      58.89 um in the POAG group vs 168.34 +/- 73.45 um in healthy controls (p =
      0.012); and in the nasal inferior zone, 113.45 +/- 49.93 um in the POAG group vs
      137.47 +/- 65.96 um in healthy controls (p = 0.049). CONCLUSION: Compared with
      healthy subjects, glaucoma patients present with peripapillary choroidal
      thinning, especially in the central superior, nasal superior, and nasal inferior
      zones. The new SS-OCT could be a useful tool to evaluate choroidal thinning, and
      it could be an additional support to facilitate glaucoma diagnosis.

PMID- 29022115
TI  - Core curriculum illustration: epiploic appendagitis.
AB  - This is the 45th installment of a series that will highlight one case per
      publication issue from the bank of cases available online as part of the American
      Society of Emergency Radiology (ASER) educational resources. Our goal is to
      generate more interest in and use of our online materials. To view more cases
      online, please visit the ASER Core Curriculum and Recommendations for Study
      online at: http://www.erad.org/page/CCIP_TOC .

PMID- 29022114
TI  - Implantable Systems for Stress Urinary Incontinence.
AB  - Stress urinary incontinence (SUI), the involuntary urine leakage due to failure
      of the urethral closure mechanism, is a global health challenge with substantial
      human suffering and socioeconomic costs. Approximately 167 million male and
      female patients are predicted to suffer from SUI in 2018, worldwide. A wide range
      of surgical interventions are available for the treatment of SUI. Severe cases,
      however, usually require the implantation of artificial urinary sphincter
      devices. This review comparatively presents and analyzes the working principles,
      as well as the challenges, associated with the current implantable SUI systems in
      clinical use. These include slings, urethral bulking agents, artificial urinary
      sphincters, and adjustable continence devices. It further reports on recent
      research progress and state-of-the-art in the field of SUI implants, including an
      original approach proposed by the authors with a pressure feedback sensory
      mechanism. The new emerging field of artificial muscle devices, including
      electroactive polymers, provides a promising innovative solution for replacing
      the weakened urethral sphincter in SUI patients.

PMID- 29022113
TI  - A Significant Association of Malnutrition with Dysphagia in Acute Patients.
AB  - Dysphagia and malnutrition seem to be associated, but little research in detail
      has been reported. We aimed to clarify the association between dysphagia and
      malnutrition by adopting accurate diagnosis and mathematical evaluation of
      dysphagia using videofluorography and nutritional assessment calculated by a well
      established nutritional risk index. We conducted a retrospective analysis of 165
      enrolled patients who were admitted to our hospital for acute diseases and
      underwent videofluorography on suspicion of dysphagia in the year 2016. We
      diagnosed high-risk dysphagia in patients with 8-point penetration-aspiration
      scale (PAS) score over 4. We used the geriatric nutritional risk index (GNRI) as
      a nutritional assessment tool. A GNRI score less than 91.2 corresponds to
      malnutrition. The median age of 165 enrolled patients was 76.0, and the number of
      female patients was 53. The mean GNRI was 81.2, and 134 patients (81.2%) had
      malnutrition. The number of the patients with a diagnosis of high-risk dysphagia
      was 54 (32.7%). The GNRI of patients with high-risk dysphagia was significantly
      less than that of patients without (mean value 77.7 +/- 10.5 vs. 83.0 +/- 10.5, P
      = 0.003). GNRI < 91.2 was independently and significantly associated with high
      risk dysphagia (OR 3.094; CI 1.057-9.058; P = 0.039). Based on the current study,
      the authors propose evaluating nutritional status to predict dysphagia risk of
      patients in the acute phase.

PMID- 29022117
TI  - Wastewater reuse in the countries of the Gulf Cooperation Council (GCC): the lost
      opportunity.
AB  - Reuse of treated wastewater is not only environmentally and financially sound, it
      is becoming indispensable for meeting the staggering water demand in certain
      regions, especially under conditions of alarming water scarcity. Reusing treated
      wastewater will help in reducing the pressure on expensive desalinated water
      production and depleting groundwater withdrawal, thereby reducing associated
      harmful environmental impacts. Reuse of wastewater in general and in the
      countries of the Gulf Cooperation Council (GCC) in particular has been a priority
      research area and has been in the media spotlight for some time, especially the
      use of tertiary quality water resources for agricultural purposes. However, reuse
      of treated wastewater is still in its primitive stage in terms of implementation
      in GCC. In addition, the overall volume of tertiary treated water that outflows
      unutilized to the sea is much greater than the volume reused. This paper provides
      a general review of and statistics on current practices of treatment of domestic
      wastewater in the GCC. The review highlights water resources, sanitation service
      coverage, wastewater treatment, effluent types, treated and reuse quantities,
      costs, and tariffs. The paper provides recommendations to improve wastewater
      treatment in the GCC to alleviate the stress on the scarce groundwater resources,
      provide a relatively inexpensive alternative to desalination, reduce the
      environmentally adverse impacts and externalities of desalination plants, and
      eliminate the discharge of untreated wastewater in coastal areas or terrestrial
      landfills.

PMID- 29022116
TI  - Two-Dimensional Temporal Clustering Analysis for Patients with Epilepsy:
      Detecting Epilepsy-Related Information in EEG-fMRI Concordant, Discordant and
      Spike-Less Patients.
AB  - EEG acquired simultaneously with fMRI (EEG-fMRI) is a multimodal method that has
      shown promise in mapping the seizure onset zone in patients with focal epilepsy.
      However, there are many instances when this method is unsuccessful or not
      applicable, and other data driven fMRI methods may be utilized. One such method
      is the two-dimensional temporal clustering analysis (2dTCA). In this study we
      compared the classic EEG-fMRI and 2dTCA performance in mapping regions related to
      the seizure onset region in 18 focal epilepsy patients (12 presenting interictal
      epileptiform discharges (IEDs), during EEG-fMRI acquisition) with Engel I or II
      surgical outcome. Activation maps of both 2dTCA timing outputs (positive and
      negative histograms) and EEG detected IEDs were computed and compared to the
      region of epilepsy surgical resection. Patients were evaluated in three
      categories based on frequency of EEG detected spiking during the MRI. EEG-fMRI
      maps were concordant to the epilepsy region in 5/12 subjects, four with frequent
      IEDs on EEG. The 2dTCA was successful in mapping 13/18 patients including 3/6
      with no IEDs detected (10/12 with IEDs detected). The epilepsy-related activities
      were successfully mapped by both methods in only 4/12 patients. This work
      suggests that the epilepsy-related information detected by each method may be
      different: while EEG-fMRI is more accurate in patients with high rather than
      lower numbers of EEG detected IEDs; 2dTCA can be useful in evaluating patients
      even when no concurrent EEG spikes are detected or EEG-fMRI is not effective.
      Therefore, our results support that 2dTCA might be an alternative for mapping
      epilepsy-related BOLD activity in negative EEG-fMRI (6/7 patients) and spike-less
      patients.

PMID- 29022118
TI  - Serological and molecular investigation of 2117-like vesiviruses in cats.
AB  - Vesivirus 2117 was first discovered as a contaminant in Chinese hamster ovary
      (CHO) cell cultures used for human drug production. Similar vesiviruses (VeVs)
      have been detected recently in dogs. In order to address the hypothesis that cats
      may also be exposed to 2117-like VeVs, in this study, we screened 236 feline sera
      using an enzyme-linked immunosorbent assay (ELISA) based on a recombinant VP1
      protein from the canine VeV Bari/212/07/ITA. IgG antibodies against the 2117-like
      VeV were detected in 37.3% of the sera tested. Also, by screening cat faecal
      specimens, the RNA of a 2117-like VeV was detected in a clinically healthy cat.

PMID- 29022119
TI  - Sex-specific cognitive-behavioural profiles emerging from individual variation in
      numerosity discrimination in Gambusia affinis.
AB  - The relationship between an individual's cognitive abilities and other
      behavioural attributes is complex, yet critical to understanding how individual
      differences in cognition arise. Here we use western mosquitofish, Gambusia
      affinis, to investigate the relationship between individual associative learning
      performance in numerical discrimination tests and independent measures of
      activity, exploration, anxiety and sociability. We found extensive and highly
      repeatable inter-individual variation in learning performance (r = 0.89; ICC =
      0.89). Males and females exhibited similar learning performance, yet differed in
      sociability, activity and their relationship between learning and
      anxiety/exploration tendencies. Sex-specific multivariate behaviour scores
      successfully predicted variation in individual learning performance, whereas
      combined sex analyses did not. Female multivariate behaviour scores significantly
      predict learning performance across females (rho = 0.80, p = 0.005) with high
      performing female learners differentiated from female non-learners and low
      performing learners by significant contributions of activity and sociability
      measures. Meanwhile, males of different learning performance levels (high-, low-
      and non-learners) were distinguished from each other by unique behavioural
      loadings of sociability, activity and anxiety/exploration scores, respectively.
      Our data suggest that despite convergence on learning performance, the sexes
      diverge in cognitive-behavioural relationships that are likely products of
      different sexual selection pressures.

PMID- 29022121
TI  - Derivation and Validation of a Novel Physiological Emergency Surgery Acuity
      Score.

PMID- 29022120
TI  - Experience-based utility and own health state valuation for a health state
      classification system: why and how to do it.
AB  - In the estimation of population value sets for health state classification
      systems such as the EuroQOL five dimensions questionnaire (EQ-5D), there is
      increasing interest in asking respondents to value their own health state,
      sometimes referred to as "experience-based utility values" or, more correctly,
      own rather than hypothetical health states. Own health state values differ to
      hypothetical health state values, and this may be attributable to many reasons.
      This paper critically examines whose values matter; why there is a difference
      between own and hypothetical values; how to measure own health state values; and
      why to use own health state values. Finally, the paper examines other ways that
      own health state values can be taken into account, such as including the use of
      informed general population preferences that may better take into account
      experience-based values.

PMID- 29022122
TI  - Association of interferon lambda polymorphisms with elevated baseline viral loads
      in chronic hepatitis C virus genotype 6 infection.
AB  - Globally, hepatitis C virus (HCV) is one of the major causes of hepatocellular
      carcinoma and liver cirrhosis. For clinical decision making, genetic variation in
      the interferon-lambda (IFNL) cluster has been utilised as a baseline predictor of
      natural and interferon-based treatment-induced viral clearance. In Vietnam, where
      HCV genotypes 1 (g1) and g6 predominate, no prior studies have been conducted
      investigating associations of IFNL3/4 polymorphisms with spontaneous clearance
      (SC) or HCV viral load (VL) in chronic infection. In this study, we have
      investigated the host genetic variations in IFNL loci to determine the
      association of IFNL3/4 polymorphisms with HCV SC and baseline VLs in a Vietnamese
      HCV-seropositive cohort. The majority of the cohort harboured major homozygous
      polymorphisms in IFNL3/4 cluster (i.e. rs12979860-CC: 82.7%; rs8099917-TT: 84.8%
      and rs368234815-TT/TT: 85.5%) and the SC rates in these groups were 15.8%, 16.3%
      and 15.7%, respectively. In the minor allele groups, the resolution rates were
      lower (12% in rs12979860 non-CC, 9.1% in rs8099917 non-TT and 9.5% in rs368234815
      non-TT/TT). Furthermore, in individuals harbouring minor alleles, females
      achieved higher SC rates than males. HCV g6-infected rs12979860 major homozygous
      individuals had significantly higher viral loads than individuals with minor
      alleles (CC: 6.56 log IU/ml vs. non-CC: 5.66 log IU/ml; P = 0.021). The
      association between IFNL3/4 genotypes with elevated HCV VL observed in HCV g6
      infected individuals may have implications for the progression of liver disease
      in Southeast Asian countries where this viral genotype predominates and therefore
      warrants further studies.

PMID- 29022123
TI  - Assessment of a closed wash system developed for processing living donor femoral
      heads.
AB  - NHS Blood and Transplant Tissue and Eye Services (TES) and Scottish National
      Blood Transfusion Services Tissues and Cells Directorate (TCD) currently bank
      whole, frozen femoral head bone from living donors who are undergoing primary hip
      replacement surgery. When required, the bone is issued to a surgeon still frozen
      on dry ice (- 79  degrees C). Consequently, the femoral head bone is not
      processed, is not sterilised and at the time of issue, it contains donor blood,
      bone marrow and associated cells. We have previously shown that, cut, shaped and
      washed bone from deceased donors can be processed to remove up to 99.9% of blood,
      bone marrow and associated cells (Eagle et al. 2015). However, cut and shaped
      bone is not suitable for some orthopaedic procedures and some orthopaedic
      surgeons do not wish to use irradiated bone; therefore in this report, a method
      has been developed in which whole femoral heads can be washed to remove donor
      blood and bone marrow components. Processing results in excess of 99% bone marrow
      component removal-soluble protein, haemoglobin and DNA; the procedure is
      performed inside a closed system, thereby eliminating the need for terminal
      sterilisation by irradiation. In addition, uniaxial testing demonstrated no
      difference in compressive strength between washed and unwashed bone. We suggest
      that this washed bone may be capable of improving incorporation after grafting
      without disturbing biomechanical properties of the graft.

PMID- 29022124
TI  - Faster photosynthetic induction in tobacco by expressing cyanobacterial
      flavodiiron proteins in chloroplasts.
AB  - Plants grown in the field experience sharp changes in irradiation due to shading
      effects caused by clouds, other leaves, etc. The excess of absorbed light energy
      is dissipated by a number of mechanisms including cyclic electron transport,
      photorespiration, and Mehler-type reactions. This protection is essential for
      survival but decreases photosynthetic efficiency. All phototrophs except
      angiosperms harbor flavodiiron proteins (Flvs) which relieve the excess of
      excitation energy on the photosynthetic electron transport chain by reducing
      oxygen directly to water. Introduction of cyanobacterial Flv1/Flv3 in tobacco
      chloroplasts resulted in transgenic plants that showed similar photosynthetic
      performance under steady-state illumination, but displayed faster recovery of
      various photosynthetic parameters, including electron transport and non
      photochemical quenching during dark-light transitions. They also kept the
      electron transport chain in a more oxidized state and enhanced the proton motive
      force of dark-adapted leaves. The results indicate that, by acting as electron
      sinks during light transitions, Flvs contribute to increase photosynthesis
      protection and efficiency under changing environmental conditions as those found
      by plants in the field.

PMID- 29022125
TI  - Parent Stress in a Randomized Clinical Trial of Atomoxetine and Parent Training
      for Children with Autism Spectrum Disorder.
AB  - We previously reported a 2 * 2 randomized clinical trial of atomoxetine (ATX) and
      parent training (PT) for attention deficit hyperactivity disorder (ADHD) symptoms
      and behavioral noncompliance in 128 children with autism spectrum disorder, ages
      5-14 years. Children were randomized to one of four conditions: ATX alone,
      placebo alone, ATX + PT, or PT + placebo. Both ATX and PT improved some indices
      of ADHD and behavioral compliance. In this report, we describe parent stress over
      time and across conditions. All four treatments improved parent self-rated stress
      from baseline to week 10. However, there were no statistically significant
      differences between treatment groups. Significantly more improvement in parent
      stress scores was observed for clinical responders than non-responders.
      ClinicalTrials.gov Title: Atomoxetine, Placebo and Parent Management Training in
      Autism (Strattera) ClinicalTrials.gov Identifier: NCT00844753.

PMID- 29022126
TI  - A systematic review of cortisol, thyroid-stimulating hormone, and prolactin in
      peripartum women with major depression.
AB  - Pregnancy and postpartum are periods of high susceptibility to major depression
      (MD) and other mood disorders. The peripartum period is also a time of
      considerable changes in the levels of hormones, including cortisol, thyroid
      stimulating hormone (TSH), prolactin, gonadotropins, and gonadal steroids. To
      investigate the relationship between mood and hormonal changes during and after
      pregnancy, we reviewed published reports of hormonal measures during this time
      frame, searched via PubMed and Web of Science. Studies were included if women in
      the antepartum or postpartum periods were clinically diagnosed with MD, and if
      there were repeated measures of cortisol, TSH, or prolactin. For these three
      hormones, the numbers of human studies that met these criteria were 15, 7, and 3,
      respectively. Convergent findings suggest that morning cortisol is reduced in
      pregnant and postpartum women with MD. Evidence did not support changes in TSH as
      a marker of MD during the peripartum period, and evidence for changes in
      prolactin in peripartum MD was equivocal. Aside from reduced morning cortisol in
      peripartum women with MD, definitive evidence for an association between specific
      hormonal fluctuations and mood disorders in the peripartum period remains
      elusive.

PMID- 29022128
TI  - Endodontic infections increase leukocyte and lymphocyte levels in the blood.
AB  - OBJECTIVES: The aim of this study was to determine whether the presence of single
      or multiple apical periodontitis (AP) alters blood cell counts and cytokine
      production. MATERIAL AND METHODS: Thirty rats were divided into three groups: a
      control group comprising rats without AP, a group called 1AP comprising rats with
      AP in one tooth, and a group called 4AP comprising rats with AP in four teeth.
      Endodontic infection was induced by pulp exposure of the first right maxillary
      molar in the 1AP group or by exposing the first and second right maxillary and
      mandibular molars in the 4AP group. A blood count and cytokine levels were
      obtained 30 days after infection by collecting blood by cardiac puncture. The
      maxillae were dissected and stained with hematoxylin and eosin to evaluate the
      inflammatory infiltrate. The data were tabulated and subjected to statistical
      analysis (P < 0.05). RESULTS: Histological analysis showed a predominance of
      mononuclear inflammatory cells. In blood, significant increase of leukocytes,
      lymphocytes, and tumor necrosis factor alpha (TNF-alpha) in 4AP compared with the
      control and 1AP groups (P < 0.05) was observed. In addition, significant decrease
      of interleukin-4 (IL-4) in 1AP and 4AP groups compared with the control was
      observed (P < 0.05). CONCLUSIONS: In the rat model, the presence of multiple AP
      can affect health by increasing lymphocyte and TNF-alpha levels in the blood.
      CLINICAL RELEVANCE: The presence of endodontic infections can interfere with the
      blood profile, altering systemic health.

PMID- 29022127
TI  - Genetic influence on femoral plaque and its relationship with carotid plaque: an
      international twin study.
AB  - To disentangle genetic and environmental influences on the development of femoral
      plaques using a population of adult twins. To evaluate the potential role of
      shared genetic and environmental factors in the co-occurrence of femoral and
      carotid plaques. The sample included 566 twins belonging to 164 monozygotic (MZ)
      and 119 dizygotic (DZ) twin pairs, who underwent peripheral arterial assessment
      by B-mode ultrasound in different centers. The variance in femoral plaques onset
      was due to genetic factors and the remaining 50% was explained by common (15%)
      and unique (35%) environmental factors. Findings on sidedness and number of
      femoral plaques indicated that also these traits were mainly under genetic
      control. No effect of common environment was found on plaques composition, and
      variability of this trait was explained by genetics (64%) and unique environment
      (36%). Covariation between the liabilities to carotid and femoral plaques was
      mainly attributed to shared genes (77%), with the remaining 23% explained by
      individual-specific environmental factors shared by the two districts. Inter
      individual differences in plaque onset as well as in their number, sidedness and
      composition are mainly genetic in origin. The results on the cooccurrence of
      carotid and femoral plaque underline the genetic role in atherogenesis.

PMID- 29022129
TI  - The Utility of Local Anesthesia for Neurosurgical Interventions in a Low-Resource
      Setting: A Case Series.
AB  - INTRODUCTION: Trauma is a major contributor to global morbidity and mortality,
      and injury to the central nervous system is the most common cause of death in
      these patients. While the provision of surgical services is being recognized as
      essential to global public health efforts, specialty areas such as neurosurgery
      remain overlooked. METHOD: This is a retrospective case review of patients with
      operable lesions, such as extra-axial hematomas and unstable depressed skull
      fractures that underwent neurosurgical interventions under local anesthesia.
      RESULTS: A total of 13 patients underwent neurosurgical intervention under local
      anesthesia. Two and three patients with burr hole decompression of epidural and
      subdural hematomas, respectively; seven patients had elevation of depressed skull
      fractures and lastly one patient had an aspiration of a brain abscess. All
      patients survived with and without residual neurological deficits. CONCLUSION:
      Access to resources and staff required to deliver general anesthesia is
      challenging in resource-poor settings. We have therefore begun performing
      emergent interventions under local anesthesia, with or without conscious
      sedation. While some patients had some minor residual weakness after the
      procedure, the degree of neurological deficit was improved from that observed
      before the procedure in all patients.

PMID- 29022130
TI  - COMPASS for Hope: Evaluating the Effectiveness of a Parent Training and Support
      Program for Children with ASD.
AB  - Despite the growing number of studies that demonstrate the importance of
      empowering parents with knowledge and skills to act as intervention agents for
      their children with autism spectrum disorder (ASD), there are limited examples of
      parent-mediated interventions that focus on problem behaviors. Additionally,
      access to ASD-trained clinicians and research supported delivery options for
      families in rural areas is severely limited. COMPASS for Hope (C-HOPE) is an 8
      week parent intervention program that was developed with the option of telehealth
      or face-to-face delivery. Parents who received C-HOPE intervention reported a
      reduction in parenting stress and an increase in competence. Parents also
      reported significant reductions in child behavior problems, both when compared to
      pre-intervention levels and to a waitlist control condition.

PMID- 29022132
TI  - An exploratory study of the electronic medical record and outpatient vascular
      neurology consultations.
AB  - We carried out a quality improvement project utilizing the electronic medical
      record (EMR) to determine (1) the quality of vascular neurologists'
      recommendations for recurrent stroke prevention and (2) primary care provider
      (PCP) acknowledgement of the vascular neurologists' recurrent stroke prevention
      recommendations and their frequency of meeting the recommended metrics for risk
      factor control and lifestyle modification. We conducted a retrospective EMR chart
      review on a convenience sample of ischemic stroke patients during two epochs.
      Data collected included risk factors, stroke subtype, and process and outcome
      guidance metrics for recurrent ischemic stroke prevention according to American
      Heart Association/American Stroke Association (AHA/ASA) recommendations. Overall,
      vascular neurologists commonly recommended appropriate AHA/ASA risk factor
      management standards, but were less likely to do so for lifestyle management.
      Improvements in the EMR system over time, including the establishment of
      guideline-driven importable recurrent stroke prevention templates, led to a high
      frequency of proper risk factor and lifestyle recommendations made by vascular
      neurologists. Statistical analysis provided further evidence that the EMR
      positively influenced the delivery of proper recurrent stroke prevention
      guidance. Although PCPs infrequently acknowledged receipt of vascular neurology
      consultations, there was a relatively high frequency of achieved risk factor
      control. The latter may be attributed at least in part to pre-existent quality
      improvement programs implemented at primary care offices. Our exploratory
      findings suggest that proper use of the EMR may heighten efforts to provide
      appropriate and consistent recurrent stroke prevention recommendations in a
      primary care setting.

PMID- 29022131
TI  - Feedback regulation of ribosome assembly.
AB  - Ribosome biogenesis is a crucial process for growth and constitutes the major
      consumer of cellular resources. This pathway is subjected to very stringent
      regulation to ensure correct ribosome manufacture with a wide variety of
      environmental and metabolic changes, and intracellular insults. Here we summarise
      our current knowledge on the regulation of ribosome biogenesis in Saccharomyces
      cerevisiae by particularly focusing on the feedback mechanisms that maintain
      ribosome homeostasis. Ribosome biogenesis in yeast is controlled mainly at the
      level of the production of both pre-rRNAs and ribosomal proteins through the
      transcriptional and post-transcriptional control of the TORC1 and protein kinase
      A signalling pathways. Pre-rRNA processing can occur before or after the 35S pre
      rRNA transcript is completed; the switch between these two alternatives is
      regulated by growth conditions. The expression of both ribosomal proteins and the
      large family of transacting factors involved in ribosome biogenesis is co
      regulated. Recently, it has been shown that the synthesis of rRNA and ribosomal
      proteins, but not of trans-factors, is coupled. Thus the so-called CURI complex
      sequesters specific transcription factor Ifh1 to repress ribosomal protein genes
      when rRNA transcription is impaired. We recently found that an analogue system
      should operate to control the expression of transacting factor genes in response
      to actual ribosome assembly performance. Regulation of ribosome biogenesis
      manages situations of imbalanced ribosome production or misassembled ribosomal
      precursors and subunits, which have been closely linked to distinct human
      diseases.

PMID- 29022133
TI  - Arginine Kinases from the Precious Corals Corallium rubrum and Paracorallium
      japonicum: Presence of Two Distinct Arginine Kinase Gene Lineages in Cnidarians.
AB  - The cDNA sequence of arginine kinase (AK) from the precious coral Corallium
      rubrum was assembled from transcriptome sequence data, and the deduced amino acid
      sequence of 364 residues was shown to conserve the structural features
      characteristic of AK. Based on the amino acid sequence, the DNA coding C. rubrum
      AK was synthesized by overlap extension PCR to prepare the recombinant enzyme.
      The following kinetic parameters were determined for the C. rubrum enzyme: K aArg
      (0.10 mM), K iaArg (0.79 mM), K aATP (0.23 mM), K iaATP (2.16 mM), and k cat
      (74.3 s-1). These are comparable with the kinetic parameters of other AKs.
      However, phylogenetic analysis suggested that the C. rubrum AK sequence has a
      distinct origin from that of other known cnidarian AKs with unusual two-domain
      structure. Using oligomers designed from the sequence of C. rubrum AK, the coding
      region of genomic DNA of another coral Paracorallium japonicum AK was
      successfully amplified. Although the nucleotide sequences differed between the
      two AKs at 14 positions in the coding region, all involved synonymous
      substitutions, giving the identical amino acid sequence. The P. japonicum AK gene
      contained one intron at a unique position compared with other cnidarian AK genes.
      Together with the observations from phylogenetic analysis, the comparison of
      exon/intron organization supports the idea that two distinct AK gene lineages are
      present in cnidarians. The difference in the nucleotide sequence between the
      coding regions of C. rubrum and P. japonicum AKs was 1.28%, which is twice that
      (0.54%) of mitochondrial DNA, is consistent with the general observation that the
      mitochondrial genome evolves slower than the nuclear one in cnidarians.

PMID- 29022134
TI  - The impact of smoking on disease activity, disability, and radiographic damage in
      rheumatoid arthritis: is cigarette protective?
AB  - The ojective of this study is to assess the effect of tobacco smoking on disease
      activity, functional ability, and joint damage in a cohort of patients with early
      onset rheumatoid arthritis (EORA). 129 EORA patients attending the Rheumatology
      Unit of the School of Medicine of the "Universidad Nacional de Colombia" and the
      "Clinica de Artritis y Rehabilitacion" in Bogota, Colombia, were enrolled in a
      prospective observational cohort study with 3-year follow-up. Clinical,
      biological, immunogenetics, and radiographic data were analyzed. Active disease
      was defined as DAS28 > 2.6. Smoking status was assessed by self-report as "never
      smokers" and "ever smokers". Patient groups with different smoking status were
      compared for RA measures. Status as "never smokers" and "ever smokers" was
      reported by 81.3 and 18.7%. Ever smokers had less risk of disability (HAQ-DI >=
      0.5) at 36 month (Ever smokers vs. Never smokers OR for HAQ >= 0.5 0.25, 95% CI
      0.06-0.97, p = 0.04). When former smokers were excluded in analysis, we found
      that current smoking was also associated with less disability and less risk of
      active disease. The percentage of erosive disease, radiographic progression, and
      SvdH score were similar in all smoking categories. In Colombian patients with
      EORA, smoking was associated with less disease activity and disability.
      Radiographic joint damage progressed at an equivalent rate in smokers and non
      smokers. These data suggest a more benign, or at least not deleterious clinical
      course in smokers with RA.

PMID- 29022135
TI  - Pcal_1311, an alcohol dehydrogenase homologue from Pyrobaculum calidifontis,
      displays NADH-dependent high aldehyde reductase activity.
AB  - Genome sequence of Pyrobaculum calidifontis, a hyperthermophilic archaeon,
      harbors three open-reading frames annotated as alcohol dehydrogenases. One of
      them, Pcal_1311, does not display a significantly high homology with any of the
      characterized alcohol dehydrogenases. Highest homology of 38% was found with the
      characterized counterpart from Geobacillus stearothermophilus. To examine the
      biochemical properties of Pcal_1311, we have cloned and functionally expressed
      the gene in Escherichia coli. Purified recombinant Pcal_1311 catalyzed the NAD(H)
      dependent oxidation of various alcohols and reduction of aldehydes, with a marked
      preference for substrates with functional group at the terminal carbon. Highest
      activity for the oxidation reaction (3 MUmol min-1 mg-1) was found with 1,4
      butanediol and for the reduction reaction (150 MUmol min-1 mg-1) with
      glutaraldehyde. Both the oxidation and reduction activities increased with the
      increase in temperature up to 80  degrees C. Recombinant Pcal_1311 was highly
      stable and retained more than 90% activity even after incubation of 180 min at 90
      degrees C. In addition to the thermostabilty, Pcal_1311 was highly stable in the
      presence of known denaturants including urea and guanidine hydrochloride. The
      high stability, particularly thermostability, and the NADH-dependent aldehyde
      reduction activity make Pcal_1311 a unique member in the alcohol dehydrogenase
      family.

PMID- 29022136
TI  - Aortic, carotid intima-media thickness and flow- mediated dilation as markers of
      early atherosclerosis in a cohort of pediatric patients with rheumatic diseases.
AB  - The aims of this study were to identify the presence of endothelial dysfunction
      as a marker of early atherosclerosis by measuring aortic and carotid intimal
      medial thickness (aIMT and cIMT) and flow-mediated dilation (FMD) and their
      correlation with traditional and no traditional risk factors for atherosclerosis
      in children with rheumatic diseases. Thirty-nine patients (mean age 15.3 +/- 5.7
      years), 23 juvenile idiopathic arthritis, 9 juvenile spondyloarthropathies, 7
      connective tissue diseases (mean disease duration and onset respectively 5 +/-
      3.6 and 10 +/- 5 years), and 52 healthy children matched for sex and age were
      enrolled. Demographic data (age, sex, familiarity for cardiovascular disease),
      traditional risk factors for atherosclerosis (BMI, active and passive smoking,
      dyslipidemia), activity disease indexes (reactive count protein, erythrocyte
      sedimentation rate) autoantibodies, and complement tests were collected. aIMT,
      cIMT, and FMD were assessed following a standardized protocol by high-resolution
      ultrasonography. Patients resulted significantly more exposed to passive smoking
      and had a lower BMI and higher homocysteine level than controls. cIMT and aIMT
      were significantly higher in patients than controls (p < 0.001) and correlated
      with age at diagnosis (p < 0.001 r 0.516 and 0.706, respectively) but not with
      mean disease duration. FMD % was significantly reduced in patients compared to
      controls (p < 0.001). Subclinical atherosclerosis occurs in pediatric rheumatic
      diseases, mainly in early onset forms, and aIMT is an earlier marker of
      preclinical atherosclerosis. Premature endothelial dysfunction could be included
      in the follow-up of children with rheumatic disorders to plan prevention
      strategies of cardiovascular disease already in pediatrics.

PMID- 29022137
TI  - Effect of different endodontic sealers and time of cementation on push-out bond
      strength of fiber posts.
AB  - OBJECTIVES: This study aims to evaluate the effect of different endodontic
      sealers (epoxy resin, eugenol, and bioceramic/calcium silicate-based) and the
      time of cementation (immediately or 7 days after canal obturation) on the bond
      strength of a fiberglass post cemented with RelyXTM ARC. MATERIAL AND METHODS:
      Eighty-four premolars were instrumented and divided into groups (n = 12)
      according to the sealer and the time of post cementation: Endofill (EN),
      Endosequence BC Sealer (BC), and AH Plus (AH) had immediately fiber post
      cementation; EN7, BC7, and AH7 had post cementation after 7 days; and control
      group (C) had fiber post cementation without endodontic sealer. Each post space
      of the root was cut into slices and submitted to push-out test. Failure mode was
      assessed. Two-way ANOVA, Tukey's, and Dunnett's tests were used for statistical
      analysis (alpha = 5%). RESULTS: The type of endodontic sealer (p < 0.001), the
      time of post cementation (p = 0.038), and the interaction sealer time (p = 0.002)
      had negative influence on bond strength of fiberglass posts cemented with RelyXTM
      ARC. AH promoted the highest bond strength mean values (21.20 MPa immediately and
      15.54 MPa at 7 days). EN (9.75 MPa immediately and 13.15 MPa at 7 days) and BC
      (10.43 MPa immediately and 5.73 MPa at 7 days) had lower bond strength than AH,
      regardless the time of cementation. CONCLUSIONS: AH was the best sealer to
      obturate the root canal when fiberglass cementation with resin-based cement is
      planned. CLINICAL RELEVANCE: The correct choice of an endodontic sealer and the
      adequate time of post cementation may avoid post dislocation caused by low bond
      strength to dentin.

PMID- 29022139
TI  - The longitudinal, bidirectional relationships between parent reports of child
      secondhand smoke exposure and child smoking trajectories.
AB  - This study examines the longitudinal relationships between child smoking and
      secondhand smoke exposure (SHSe). Participants were 222 parent-child dyads. The
      parents smoked, had a child with (48%) or without asthma, and were enrolled in a
      smoking/health intervention. Parent-reported child SHSe was measured at baseline
      and 4, 6, and 12-month follow-ups; self-reported child smoking was assessed at
      these points and at 2-months. A parallel process growth model was used. Baseline
      child SHSe and smoking were correlated (r = 0.30). Changes in child SHSe and
      child smoking moved in tandem as evidenced by a correlation between the linear
      slopes of child smoking and SHSe (r = 0.32), and a correlation between the linear
      slope of child smoking and the quadratic slope of child SHSe (r = - 0.44).
      Results may inform interventions with the potential to reduce child SHSe and
      smoking among children at increased risk due to their exposure to parental
      smoking.

PMID- 29022138
TI  - Associated and mediating variables related to quality of life among service users
      with mental disorders.
AB  - PURPOSE: This study aimed to identify variables associated with quality of life
      (QoL) and mediating variables among 338 service users with mental disorders in
      Quebec (Canada). Data were collected using nine standardized questionnaires and
      participant medical records. METHODS: Quality of life was assessed with the
      Satisfaction with Life Domains Scale. Independent variables were organized into a
      six-block conceptual framework. Using structural equation modeling, associated
      and mediating variables related to QoL were identified. RESULTS: Lower
      seriousness of needs was the strongest variable associated with QoL, followed by
      recovery, greater service continuity, gender (male), adequacy of help received,
      not living alone, absence of substance use or mood disorders, and higher
      functional status, in that order. Recovery was the single mediating variable
      linking lower seriousness of needs, higher service continuity, and reduced
      alcohol use with QoL. Findings suggest that greater service continuity creates
      favorable conditions for recovery, reducing seriousness of needs and increasing
      QoL among service users. Lack of recovery-oriented services may affect QoL among
      alcohol users, as substance use disorders were associated directly and negatively
      with QoL. CONCLUSIONS: Decision makers and mental health professionals should
      promote service continuity, and closer collaboration between primary care and
      specialized services, while supporting recovery-oriented services that encourage
      service user involvement in their treatment and follow-up. Community-based
      organizations should aim to reduce the seriousness of needs particularly for
      female service users and those living alone.

PMID- 29022141
TI  - A new species of Trichodina Ehrenberg, 1830 (Ciliophora: Trichodinidae) infecting
      farmed Clarias gariepinus (Burchell) (Siluriformes: Clariidae) in Cuba.
AB  - A new species of Trichodina Ehrenberg, 1830 collected from the skin and fins of
      farmed North African catfish Clarias gariepinus (Burchell) fingerlings, is
      described. The new species can be distinguished from other trichodinids by the
      characteristics of the adhesive disc, especially by the great number of
      denticles. Trichodina merciae n. sp. is morphologically similar to T. renicola
      (Mueller, 1931) and T. marplatensis Martorelli, Marcotegui & Alda, 2008, in the
      number of denticles, but differs in the morphometric data, denticle morphology,
      environment and location. Trichodina merciae n. sp. has broad sickle-shaped
      blades and thin, straight rays, while T. marplatensis has broad club-shaped
      blades and wide S-shaped rays. Besides, denticle length, blade length, ray
      length, width of central part and denticle span of the new species are greater
      than T. marplatensis. However, the diameter of denticle ring and the diameter of
      the central area in T. marplatensis is larger than the ones in T. merciae n. sp.
      This is the first record of freshwater ectoparasite trichodinid with an average
      number of denticles greater than 50.

PMID- 29022140
TI  - Experimental Study of the Protective Effect of Simvastatin on Lung Injury in Rats
      with Sepsis.
AB  - Simvastatin, which is primarily prescribed to lower cholesterol, may also
      mitigate lung injury caused by sepsis, although the mechanisms remain elusive.
      This study aimed to evaluate the protective effect of simvastatin on acute lung
      injury in rats with sepsis and to investigate possible mechanisms. Male Wistar
      rats were pretreated with simvastatin (0.2 MUg/g) for 1 week before cecal
      ligation and puncture. Treatment with simvastatin demonstrated significant
      decreases in the concentration of protein, TNF-alpha, IL-1beta, IL-6, and
      lipocalin 2, and the number of polymorphonuclear neutrophils in bronchoalveolar
      lavage fluid in septic rats. In addition, simvastatin also reduced levels of
      Evans blue, malondialdehyde, 8-hydroxy-2'-deoxyguanosine, and wet/dry lung weight
      ratios, and increased the activity of superoxide dismutase in lung tissue.
      Furthermore, expression levels of TLR4, NF-kappaB p65, and active caspase-3
      proteins and Bax mRNA were also decreased by simvastatin. H&E staining showed
      that severe lung injury occurred in the sepsis group and that lung injury was
      reduced by treatment with simvastatin. In conclusion, simvastatin improved
      endothelial permeability and mitigated the inflammatory response of lung tissue,
      the oxidative stress response, and cell apoptosis by inhibiting the TLR4/NF
      kappaB signaling pathway, thereby alleviating sepsis-induced acute lung injury in
      rats.

PMID- 29022142
TI  - Microvesicle-mediated delivery of miR-1343: impact on markers of fibrosis.
AB  - Tissue fibrosis, the development of fibrous connective tissue as a result of
      injury or damage, is associated with many common diseases and cannot be treated
      effectively. The complex biological processes accompanying fibrosis often involve
      aberrant signaling through the transforming growth factor beta (TGF-beta)
      pathway. In the search for mechanisms to repress this signaling, microRNAs have
      emerged as a novel class of molecules capable of targeting single members of the
      TGF-beta pathway, or the pathway as a whole. We previously identified miR-1343 as
      a potent repressor of TGF-beta signaling and fibrosis through the direct
      attenuation of both canonical TGF-beta receptors. Here, we build upon our
      previous findings to better characterize the function of endogenous miR-1343 in
      normal biology and examine the potential role of exogenous miR-1343 as a
      repressor of TGF-beta signaling. CRISPR/Cas9-mediated deletion of miR-1343 from
      A549 lung epithelial cells impacts several processes and genes implicated in
      fibrosis and known to be TGF-beta pathway effectors. Moreover, the responses are
      opposite to those we observed previously when miR-1343 was overexpressed in the
      same cell type. We also show that miR-1343 can be shuttled into exosomes, a type
      of extracellular vesicle that are exported by cells into the surrounding medium
      and can be absorbed by distant target cells. miR-1343 delivered into primary lung
      fibroblasts by exosomes has a measurable function in reducing TGF-beta signaling
      and markers of fibrosis. These results highlight a role for miR-1343 in fine
      tuning the TGF-beta pathway and suggest its use as a therapeutic in fibrotic
      disease.

PMID- 29022144
TI  - A Qualitative Evaluation of Engagement and Attrition in a Nurse Home Visiting
      Program: From the Participant and Provider Perspective.
AB  - Beginning parenting programs in the prenatal and early postnatal periods have a
      large potential for impact on later child and maternal outcomes. Home-based
      parenting programs, such as the Nurse Family Partnership (NFP), have been
      established to help address this need. Program reach and impact is dependent on
      successful engagement of expecting mothers with significant risks; however, NFP
      attrition rates remain high. The current study qualitatively examined engagement
      and attrition from the perspectives of NFP nurses and mothers in order to
      identify mechanisms that enhance service engagement. Semi-structured interviews
      were conducted in focus groups composed of either engaged (27 total mothers) or
      unengaged (15 total mothers) mothers from the NFP program. NFP nurses (25 total
      nurses) were recruited for individual semi-structured interviews. Results suggest
      that understanding engagement in the NFP program requires addressing both initial
      and sustained engagement. Themes associated with enhanced initial engagement
      include nurse characteristics (e.g., flexible, supportive, caring) and
      establishment of a solid nurse-family relationship founded on these
      characteristics. Factors impacting sustained engagement include nurse
      characteristics, provision of educational materials on child development,
      individualized services for families, and available family support. Identified
      barriers to completing services include competing demands and lack of support.
      Findings of this study have direct relevance for workforce planning, including
      hiring and training through integrating results regarding effective nurse
      characteristics. Additional program supports to enhance parent engagement may be
      implemented across home-based parenting programs in light of the current study's
      findings.

PMID- 29022143
TI  - Comorbidity of gastrointestinal disorders, migraine, and tension-type headache: a
      cross-sectional study in Iran.
AB  - Migraine can be accompanied by some gastrointestinal (GI) disorders. In this
      study, we aimed to investigate the relationship between migraine and tension-type
      headache (TTH) and different lower and upper GI disorders as well as non
      alcoholic fatty liver (NAFLD) and cholelithiasis. This cross-sectional study
      included 1574 overweight and obese participants who were referred to the Obesity
      Research Center of Sina Hospital, Tehran, Iran. The diagnosis of migraine and TTH
      was made by an expert neurologist based on the international classification of
      headache disorders-III beta (ICHD III beta). GI disorders, including irritable
      bowel syndrome (IBS), constipation, heartburn, dyspepsia, non-alcoholic fatty
      liver (NAFLD), and cholelithiasis, were diagnosed by a gastroenterology
      specialist. The overall mean age of participants was 37.44 +/- 12.62. A total of
      181 (11.5%) migraine sufferers (with and without aura) and 78 (5%) TTH subjects
      were diagnosed. After adjusting for potential confounders by multivariable
      regression models, migraine had significant association with IBS (OR = 5.16, 95%
      CI = 2.07-12.85, P = 0.000), constipation (OR = 3.96, 95% CI = 2.25-6.99, P =
      0.000), dyspepsia (OR = 4.12, 95% CI = 2.63-6.45, P = 0.000), and heartburn (OR =
      5.03, 95% CI 2.45-10.33, P = 0.000), while the association between migraine and
      NAFLD was marginally significant (OR = 2.03, 95% CI = 0.98-4.21, P = 0.055).
      Furthermore, the prevalence of NAFLD (OR = 2.93, 95% CI 1.29-6.65, P = 0.010) and
      dyspepsia (OR = 4.06, 95% CI = 2.24-7.34, P = 0.000) was significantly higher in
      TTH patients than the headache-free group. These findings show an association
      between GI disorders and primary headaches especially migraine and are,
      therefore, of value to the management of migraine and TTH. Further studies should
      investigate the etiology of the relationship between all subtypes of primary
      headaches and GI disorders.

PMID- 29022145
TI  - Autoimmune enteropathies.
AB  - Autoimmune enteropathy (AIE) is a rare condition characterized by intractable
      diarrhea and immune-mediated injury of the intestinal mucosa. As the clinical and
      histopathologic manifestations of this disease are highly variable, its diagnosis
      is challenging for both clinicians and pathologists. In fact, the term autoimmune
      enteropathies is likely more appropriate since the clinicopathologic
      manifestations are observed in association with a heterogeneous group of
      disorders. The pathophysiology of AIE has not been fully elucidated. It appears
      to result from dysregulation of intestinal immunity and particularly in children,
      often presents in association with immunodeficiency. The overarching
      histopathologic changes seen in AIE include mucosal inflammation and epithelial
      injury, although this can manifest in the form of different patterns. Recognition
      of the clinical settings and of the various histologic patterns can aid the
      pathologist in establishing the correct diagnosis.

PMID- 29022146
TI  - Cupriavidus malaysiensis sp. nov., a novel poly(3-hydroxybutyrate-co-4
      hydroxybutyrate) accumulating bacterium isolated from the Malaysian environment.
AB  - Bacterial classification on the basis of a polyphasic approach was conducted on
      three poly(3 hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] accumulating
      bacterial strains that were isolated from samples collected from Malaysian
      environments; Kulim Lake, Sg. Pinang river and Sg. Manik paddy field. The Gram
      negative, rod-shaped, motile, non-sporulating and non-fermenting bacteria were
      shown to belong to the genus Cupriavidus of the Betaproteobacteria on the basis
      of their 16S rRNA gene sequence analyses. The sequence similarity value with
      their near phylogenetic neighbour, Cupriavidus pauculus LMG3413T, was 98.5%.
      However, the DNA-DNA hybridization values (8-58%) and ribotyping analysis both
      enabled these strains to be differentiated from related Cupriavidus species with
      validly published names. The RiboPrint patterns of the three strains also
      revealed that the strains were genetically related even though they displayed a
      clonal diversity. The major cellular fatty acids detected in these strains
      included C15:0 ISO 2OH/C16:1 omega7c, hexadecanoic (16:0) and cis-11-octadecenoic
      (C18:1 omega7c). Their G+C contents ranged from 68.0  to 68.6 mol%, and their
      major isoprenoid quinone was Ubiquinone Q-8. Of these three strains, only strain
      USMAHM13 (= DSM 25816 = KCTC 32390) was discovered to exhibit yellow pigmentation
      that is characteristic of the carotenoid family. Their assembled genomes also
      showed that the three strains were not identical in terms of their genome sizes
      that were 7.82, 7.95 and 8.70 Mb for strains USMAHM13, USMAA1020 and USMAA2-4,
      respectively, which are slightly larger than that of Cupriavidus necator H16
      (7.42 Mb). The average nucleotide identity (ANI) results indicated that the
      strains were genetically related and the genome pairs belong to the same species.
      On the basis of the results obtained in this study, the three strains are
      considered to represent a novel species for which the name Cupriavidus
      malaysiensis sp. nov. is proposed. The type strain of the species is USMAA1020T
      (= DSM 19416T = KCTC 32390T).

PMID- 29022147
TI  - Interventional Activism in Gastroenterology.

PMID- 29022148
TI  - Utilizing Education and Perspective Taking to Remediate the Stigma of Taking
      Antidepressants.
AB  - The incidence of depression has been increasing. One of the best interventions
      for depression is taking antidepressant medications. However, the stigma of
      taking antidepressants has been shown to be a barrier not only to seeking an
      antidepressant regimen but also adhering to it. This may have negative
      consequences for people who suffer from depression. Thus, in two studies, we
      investigate the incidence of felt stigma of taking antidepressants among
      clinically depressed individuals who take antidepressants and the effectiveness
      of two possible interventions to reduce this stigma among others. Study 1
      revealed that stigma toward individuals who take antidepressants is a reality,
      either because people were not educated about depression and antidepressants, or
      because they did not show empathy or did not take on perspectives from the
      victim's point-of-view. Based on these results, we used an experimental design in
      Study 2 to investigate the effects of education and perspective-taking
      interventions in diminishing the stigma of taking antidepressants. These results
      suggest that participant gender played a moderating role in the effectiveness of
      education and perspective taking, such that a combination of the two
      interventions resulted in lower stigma for men but not for women. These results
      suggest that people can be trained (using a simple, low-fidelity intervention) to
      be more accepting of antidepressant use among their friends, family members, and
      colleagues, resulting in better outcomes for those who benefit from taking
      antidepressants.

PMID- 29022149
TI  - Brief Report: Self-Reported Academic, Social, and Mental Health Experiences of
      Post-Secondary Students with Autism Spectrum Disorder.
AB  - Increasing numbers of individuals with autism spectrum disorder (ASD) are
      enrolling in post-secondary academic institutions. However, research indicates
      that post-secondary students with ASD are struggling more than their typically
      developing peers, with high rates of loneliness, anxiety, depression, and an
      increased incidence of dropping-out before completion of their degrees. The
      current study utilized an online survey to gain insight into the self-reported
      academic, social, and mental health experiences of post-secondary students with
      ASD. Participants reported high levels of academic comfort, but struggled with
      issues of isolation/loneliness and high levels of stress, anxiety, and
      depression. Of greatest concern, were the nearly three-quarters of participants
      who reported lifetime suicidal behaviors. Further analysis on collected data and
      implications of findings are discussed.

PMID- 29022150
TI  - Healing of the perineal wound after proctectomy in Crohn's disease patients: only
      preoperative perineal sepsis predicts poor outcome.
AB  - BACKGROUND: The aim of our study was to assess perineal wound healing in patients
      with Crohn's disease (CD) who undergo proctectomy or proctocolectomy with end
      ileostomy and to evaluate the influence of various factors including types of
      perineal dissection on eventual wound healing. METHODS: Data for patients with CD
      who underwent proctectomy or total proctocolectomy with end ileostomy from 1995
      to 2012 were reviewed. The relationship between perineal wound healing and
      demographics, patient characteristics, and other factors was assessed using
      univariate and multivariate analyses. RESULTS: The perineal wound healed by 12
      weeks in 72 (52.9%) out of 136 patients (63.2% female, mean age 41 +/- 13 years);
      delayed healing occurred in 35 patients (25.7%), and in 29 patients (21.3%),
      there was non-healing. On multivariate analysis, the only factor associated with
      delayed healing and non-healing was preoperative perineal sepsis (p = 0.001).
      CONCLUSIONS: After proctectomy or proctocolectomy for CD, perineal wound healing
      is poor and poses a particular challenge for patients with preoperative perineal
      sepsis. These findings support a preoperative discussion regarding CD patients
      that examines potential outcomes and the consideration of measures such as the
      initial creation of defunctioning ostomy or control/drainage of local sepsis
      prior to proctectomy.

PMID- 29022152
TI  - Microwave-Assisted Combustion Synthesis of ZnO:Eu Nanoparticles: Effect of Fuel
      Types.
AB  - Nanoparticles of Europium oxide doped with Zinc oxide were synthesized via
      microwave-assisted combustion method. Citric acid as a simultaneous fuel and
      chelating agent and glycine as a fuel and mixture of these fuels were sleeted. X
      Ray diffraction patterns (XRD) indicated the formation of ZnO structure with a
      few amount of Eu2O3 phase. Fourier transformation infra red (FTIR) spectra reveal
      the increase of ZnO4 bonds with glycine content of fuels mixture. Scanning
      electron microscope (SEM) images showed the conversion of nanosphere to spongy
      like structure with respect to change of fuel mixtures from citric to glycine.
      From transmission electron microscopy (TEM) nanoparticles of a mean size 30 nm
      are observed Green fluorescence emission of different samples was due to
      activation of self activated center of ZnO structure through transition of
      electron from Eu3+ to Vzn sites.

PMID- 29022151
TI  - Comparative Safety of Targeted Therapies for Metastatic Colorectal Cancer between
      Elderly and Younger Patients: a Study Using the International Pharmacovigilance
      Database.
AB  - BACKGROUND: Metastatic colorectal cancer (mCRC) is increasingly treated using
      targeted therapies. Post-marketing safety of these agents is understudied,
      especially in the elderly. OBJECTIVE: This study aimed to compare, according to
      age, the adverse drug reactions (ADRs) of targeted therapies used for mCRC in
      real life. PATIENTS AND METHODS: An extraction of VigiBase, which contains World
      Health Organization individual case safety reports (ICSRs), was performed. All
      ADR reports with aflibercept, bevacizumab, cetuximab, panitumumab, or regorafenib
      used in CRC were considered. For all drugs, chi-square tests were used to compare
      frequencies of serious ADRs between patients aged >=75 and <75 years. For
      selected ADRs and each drug, the drug-ADR association compared to other
      anticancer drugs was estimated through the proportional reporting ratio (PRR) in
      both age groups. RESULTS: There were 21,565 ICSRs included, among which 74% were
      serious and 11% were fatal. Median age was 64 years (Inter Quartile Range = 56
      71) and 15% of patients were aged >=75; 57% were male. Serious ICSRs accounted
      for 47,292 ADRs. Neutropenia was not more reported in elderly for all drugs while
      diarrhea was more reported in elderly for panitumumab. Cardiac disorders were
      more reported in elderly patients, in particular heart failure, especially for
      bevacizumab, cetuximab, and regorafenib, as were respiratory, thoracic, and
      mediastinal disorders. Most of PRR were not different between the two groups,
      except encephalopathies, which were significantly associated with bevacizumab in
      the elderly only. CONCLUSIONS: ADRs related to targeted therapies used for mCRC
      treatment were different across age groups; yet, not systematically more reported
      or worse in elderly patients. Selected elderly patients could, therefore, be
      treated with these targeted therapies.

PMID- 29022153
TI  - Practical considerations when analyzing discrete survival times using the grouped
      relative risk model.
AB  - The grouped relative risk model (GRRM) is a popular semi-parametric model for
      analyzing discrete survival time data. The maximum likelihood estimators (MLEs)
      of the regression coefficients in this model are often asymptotically efficient
      relative to those based on a more restrictive, parametric model. However, in
      settings with a small number of sampling units, the usual properties of the MLEs
      are not assured. In this paper, we discuss computational issues that can arise
      when fitting a GRRM to small samples, and describe conditions under which the
      MLEs can be ill-behaved. We find that, overall, estimators based on a penalized
      score function behave substantially better than the MLEs in this setting and, in
      particular, can be far more efficient. We also provide methods of assessing the
      fit of a GRRM to small samples.

PMID- 29022154
TI  - Runoff of the herbicides triclopyr and glufosinate ammonium from oil palm
      plantation soil.
AB  - This study focused on the residue detection of the herbicides triclopyr and
      glufosinate ammonium in the runoff losses from the Tasik Chini oil palm
      plantation area and the Tasik Chini Lake under natural rainfall conditions in the
      Malaysian tropical environment. Triclopyr and glufosinate ammonium are post
      emergence herbicides. Both herbicides were foliar-sprayed on 0.5 ha of oil palm
      plantation plots, which were individualized by an uneven slope of 10-15%. Samples
      were collected at 1, 3, 7, 15, 30, 45, 60, 90, and 120 days after treatment. The
      concentrations of both herbicides quickly diminished from those in the analyzed
      sample by the time of collection. The highest residue levels found in the field
      surface leachate were 0.031 (single dosage, triclopyr), 0.041 (single dosage,
      glufosinate ammonium), 0.017 (double dosage, triclopyr), and 0.037 MUg/kg (double
      dosage, glufosinate ammonium). The chromatographic peaks were observed at "0" day
      treatment (2 h after herbicide application). From the applied active ingredients,
      the triclopyr and glufosinate losses were 0.025 and 0.055%, respectively. The
      experimental results showed that both herbicides are less potent than other
      herbicides in polluting water systems because of their short persistence and
      strong adsorption onto soil clay particles.

PMID- 29022155
TI  - Some immunological responses of common carp (Cyprinus carpio) fingerling to acute
      extremely low-frequency electromagnetic fields (50 Hz).
AB  - Increasing of anthropogenic electromagnetic fields in aquatic environments has
      been recently become the core of attention. In this study, the effect of
      extremely low-frequency electromagnetic fields (50 Hz) on immune status and
      metabolic markers of common carp fingerling was assessed. The fish were exposed
      to extremely low-frequency electromagnetic fields at four intensities of 0.1,
      0.5, 1, and 2 mT only once for 2 h; then, they were reared for 60 days. Results
      showed that the levels of aspartate aminotransferase (AST) and alanine
      transaminase (ALT) and alkaline phosphatase (ALP) were increased with an increase
      in the electromagnetic field intensity on 15 and 60 days post exposure. A
      significant increase was obtained in these enzyme levels in all the tested
      intensities compared to the control one (p < 0.05), with a maximum value measured
      in 2-mT trail. Conversely, with an increasing in the electromagnetic intensity,
      the levels of C3, C4, and lysozyme were reduced in all the treated groups in
      comparison with the control group (p < 0.05). The results suggested a significant
      impact of electromagnetic on fish immunophysiological functions. Therefore, it is
      required to have serious attention in aquatic ecosystems.

PMID- 29022156
TI  - Recent advances in imine reductase-catalyzed reactions.
AB  - Imine reductases are nicotinamide-dependent enzymes that catalyze the asymmetric
      reduction of various imines to the corresponding amine products. Owing to the
      increasing roles of chiral amines and heterocyclic compounds as intermediates for
      pharmaceuticals, the demand for novel selective synthesis strategies is vitally
      important. Recent studies have demonstrated the discovery and structural
      characterization of a number of stereoselective imine reductase enzymes. Here, we
      highlight recent progress in applying imine reductases for the formation of
      chiral amines and heterocycles. It particularly focuses on the utilization of
      imine reductases in reductive aminations of aldehydes and ketones with various
      amine nucleophiles, one of the most powerful reactions in the synthesis of chiral
      amines. Second, we report on the synthesis of saturated substituted N
      heterocycles by combining them with further biocatalysts, such as carboxylic acid
      reductases, oxidases or transaminases. Finally, we summarize the latest
      applications of imine reductases in the promiscuous asymmetric hydrogenation of a
      highly reactive carbonyl compound and the engineering of the cofactor specificity
      from NADPH to NADH.

PMID- 29022157
TI  - Radiosurgery in trochlear and abducens nerve schwannomas: case series and
      systematic review.
AB  - INTRODUCTION: Schwannomas involving the occulomotor cranial nerves  (CNs; III, IV
      and VI), can be disabling, due to the associated diplopia and decreased quality
      of life and are extremely rare. We evaluated the role of Gamma Knife surgery
      (GKS) in these cases. METHODS: Five patients with CN IV and VI schwannomas (three
      and two, respectively) were treated in Lausanne University Hospital between 2010
      and 2015. Four benefitted from upfront GKS and one from a combined approach
      (planned subtotal resection followed by GKS), due to a large preoperative tumour
      volume (size, 3 * 2 * 2.5 cm; volume, 7.9 ml), with symptomatic mass effect and
      oedema, as well as an entrapement cyst at the brainstem interface, in a young
      patient. Neuro-ophtalmological evaluation was performed at baseline and during
      each follow-up time-point. A systematic literature review is presented and
      compared to the present report. RESULTS: The mean follow-up was 44.4 months (12
      54). Initial clinical presentation was diplopia in four cases and cavernous sinus
      syndrome in one. The marginal dose was 12 Gy in all cases. The mean target volume
      was 1.51 cm3 (0.086-5.8). The mean prescription isodose volume (PIV) was 1.71 cm3
      (0.131-6.7). At last follow-up, all patients presented with disappearance of the
      baseline symptoms. Tumour control was achieved in 100%, with decrease in volume
      in all cases. The systematic review analysed 11 peer-reviewed studies, with a
      total of 35 patients. For uniformly reported CN VI, the mean marginal radiation
      dose ranged between 12 and 12.5 Gy, with disappearance of symptoms in 12.5%,
      improvement in 31.25%, stabilisation in 6.25%, worsening in 12.5%. Tumour volume
      decreased in all cases. CONCLUSIONS: Our data suggest that first intention GKS is
      a safe and effective option for patients with small to medium size oculomotor
      schwannomas, providing a high rate of clinical alleviation and tumour control.
      When the initial tumour volume is too large for first intention GKS, a combined
      approach with planned subtotal resection followed by GKS can be performed, with
      favourable and comparable outcomes as in upfront GKS.

PMID- 29022158
TI  - Clinical utility of bioelectrical impedance analysis in patients with
      locoregional muscle invasive or metastatic urothelial carcinoma: a subanalysis of
      changes in body composition during neoadjuvant systemic chemotherapy.
AB  - PURPOSE: The aim of this study was to determine the clinical utility of
      bioelectrical impedance analysis (BIA) in a cohort of patients with advanced
      urothelial carcinoma (UC). METHODS: We prospectively evaluated body composition
      in 35 patients with locoregional muscle invasive (>= T2 and N0-2M0) or metastatic
      UC. Body composition was evaluated using multifrequency BIA at baseline (n = 35)
      and during chemotherapy in patients receiving neoadjuvant chemotherapy (n = 14).
      The BIA-predicted body composition index was compared with the computed
      tomography-measured muscle index and the prognostic nutrition index. Changes in
      body composition during neoadjuvant chemotherapy were recorded and compared with
      the incidence of hematological adverse events. RESULTS: There was a significant
      correlation between the BIA-predicted skeletal muscle index and the computed
      tomography-measured skeletal muscle index (P = 0.004), while there was no
      significant correlation between the prognostic nutrition index and the BIA
      predicted nutrition index. After the completion of 3 cycles of neoadjuvant
      chemotherapy, the skeletal muscle index showed a significant decrease (P =
      0.016), while the total body fat mass (P = 0.025), body fat percentage (P =
      0.013), and body mass index (P = 0.004) showed a significant increase (a tendency
      toward "sarcopenic obesity"). Patients who experienced grade 2-3 anemia during
      neoadjuvant chemotherapy showed a significantly lower increase in body mass index
      compared with patients who did not experience high-grade toxicities (P = 0.032).
      CONCLUSIONS: BIA could contribute to other methods of nutrition and muscle
      assessment for pretreatment risk stratification in patients with UC. Further
      study of a larger cohort is required to elucidate the clinical impact of changes
      in body composition during chemotherapy.

PMID- 29022159
TI  - Modulation of trace element bioavailability for two earthworm species after
      biochar amendment into a contaminated technosol.
AB  - Biochars are used as amendments to improve soil quality, but their effects on
      edaphic organisms such as earthworms remain controversial. This study aimed to
      assess the effects of adding a poultry manure-derived biochar into a contaminated
      technosol on trace element (TE) (i.e. As, Cd, Cu, Pb, and Zn) bioavailability for
      two earthworm species, Aporrectodea icterica and Aporrectodea longa. Three
      components of the bioavailability concept were determined using a pot experiment:
      (1) total soil TE (potentially reactive) and TE concentrations in the soil pore
      water (environmental availability), (2) TE concentrations in depurated whole
      earthworm bodies (environmental bioavailability) and (3) ecophysiological and
      biochemical effects on earthworms (toxicological bioavailability). Biochar
      addition increased TE concentrations in the soil pore water respectively from
      1.8, 2.7, 9.4, 0.7 and 959 to 6, 6.2, 19.3, 6.9, and 3003 ug L-1 for As, Cd, Cu,
      Pb and Zn. Biochar addition did not influence TE environmental bioavailability
      for earthworms, except a decreased As concentration (32.5 to 15.2 ug g-1) in A.
      icterica. This suggests an inter-specific variability in As homeostasis in the
      Aporrectodea genus. In line with this internal As decrease, the Glutathione-S
      transferase (GST) activity decreased by 42% and protein and lipid contents
      slightly increased (14 and 25%, respectively) in A. icterica tissues. The body
      weight of both earthworm species decreased for the biochar-amended soil.
      Environmental TE availability depended on both the biochar addition and the
      earthworm activity in the contaminated soil, while environmental and
      toxicological bioavailabilities resulted from the earthworm species, the targeted
      TE and biochar supply to the soil.

PMID- 29022160
TI  - A Catalyst from Burkholderia cenocepacia for Efficient Anti-Prelog's Bioreduction
      of 3,5-Bis(Trifluoromethyl) Acetophenone.
AB  - (R)-3, 5-Bis(trifluoromethyl)phenyl ethanol is a key chiral intermediate for the
      synthesis of aprepitant. Through a genome mining approach, an NADPH-dependent
      short-chain dehydrogenases derived from Burkholderia cenocepacia (Bc-SDR) was
      discovered with excellent anti-Prelog's stereoselectivity of reducing 3, 5
      bis(trifluoromethyl) acetophenone. The enzyme with 247 amino acids was
      successfully expressed in Escherichia coli and the molecular weight was about 26
      kDa. Optimization of reaction conditions showed that the optimum temperature and
      pH of the enzyme was 25  degrees C and pH 7.0, respectively. Strong enhancement
      of enzyme activity was observed in the presence of 1 mM Mn2+. In addition, Bc-SDR
      exhibited (R)-selective enantioselectivity toward acetophenone derivatives, which
      makes it a potential catalyst for obtaining aromatic chiral alcohols as useful
      blocks in pharmaceutical applications.

PMID- 29022162
TI  - The Effect of Religious Belief and Forgiveness on Coping with Diabetes.
AB  - We aimed to investigate the relationship of religious beliefs and forgiveness in
      diabetic patients with various sociodemographic characteristics, emotional
      problems and glycaemic control. The study comprises 100 patients diagnosed with
      type 2 DM. We used a data collection form, the Scale of Forgiveness and
      Religiosity (SFR), Problem Areas in Diabetes Scale (PAID), Beck Depression
      Inventory (BDI), State-Trait Anxiety Inventory (STAI) and the Audit of Diabetes
      Dependent Quality of Life (ADDQoL). We also recorded blood glucose and HbA1c test
      results. A statistically significant relationship was determined only between the
      scores of the STAI-I and the religious belief scales (r = 0.198, p = 0.049). A
      statistically significant negative relationship was determined between the
      forgiveness scale points and the BDI (r = 0.326, p = 0.001), the STAI-II (r =
      0.308, p = 0.002) and PAID (r = 0.313, p = 0.001) and a positive correlation with
      ADDQoL (r = 0.284, p = 0.004). To conclude, forgiveness by patient himself or
      others reduced the emotional problems which were experienced related to diabetes
      by reducing stress levels and could increase quality of life.

PMID- 29022164
TI  - Is use of glycine-containing drugs in anesthesia safe?

PMID- 29022163
TI  - Comparison of central corneal thickness with four different optical devices.
AB  - BACKGROUND: To compare the consistency between the average scores of the contact
      central corneal thickness measurements from ultrasound pachymetry devices still
      gold standard, such as iPac(r) and Echoscan US-500, and noncontact measurements
      via Pentacam HR and Sirius topography. METHODS: This prospective study,
      subsequently admitted to the ophthalmology department, 76 healthy individuals
      were performed. The measurements were repeated three times for each eye, and
      average scores were statistically analyzed on the same day and almost at the same
      time. While measuring the eyes, Pentacam HR, Sirius topography, iPac(r), and
      Echoscan US-500 were used, respectively. The inter-rater agreement of
      measurements from the devices was assessed with intraclass correlation
      coefficient, and 95% Confidence Interval and p values demonstrating statistically
      significance were also presented. In the graphical assessment of the agreement,
      the Bland-Altman graph was used. RESULTS: Among 76 study participants, 43 (56.6%)
      were composed of women, and age level was 38.6 +/- 12.5 years, ranging between 18
      and 69. It was observed that the highest agreement was between the measurements
      obtained from Echoscan US-500 and iPac(r) devices, but the agreement between the
      measurements of different devices was higher than 0.90. Bland-Altman graphics
      were also investigated; the results of four different devices were seen to be
      consistent with one another. CONCLUSIONS: Therefore, the devices we compared in
      the study can be used as alternatives to one another due to the higher
      consistency between CCT measurements provided with through UP devices of Echoscan
      US-500 and iPac(r), and Pentacam HR and Sirius topography devices. CLINICAL TRIAL
      REGISTRATION NUMBER: 2016/112.

PMID- 29022161
TI  - POM-1 inhibits P2 receptors and exhibits anti-inflammatory effects in
      macrophages.
AB  - Extracellular nucleotides can modulate the immunological response by activating
      purinergic receptors (P2Rs) on the cell surface of macrophages, dendritic, and
      other immune cells. In particular, the activation of P2X7R can induce release of
      cytokines and cell death as well as the uptake of large molecules through the
      cell membrane by a mechanism still poorly understood. Polyoxotungstate-1 (POM-1)
      has been proposed as a potent inhibitor of ecto-nucleotidases, enzymes that
      hydrolyze extracellular nucleotides, regulating the activity of P2Rs. However,
      the potential impact of POM-1 on P2Rs has not been evaluated. Here, we used
      fluorescent dye uptake, cytoplasmic free Ca2+ concentration measurement, patch
      clamp recordings, scanning electron microscopy, and quantification of
      inflammatory mediators to investigate the effects of POM-1 on P2Rs of murine
      macrophages. We observed that POM-1 blocks the P2YR-dependent cytoplasmic Ca2+
      increase and has partial effects on the cytoplasmic Ca2+, increasing dependence
      on P2XRs. POM-1 can inhibit the events related with ATP-dependent inflammasome
      activation, anionic dye uptake, and also the opening of large conductance
      channels, which are associated with P2X7R-dependent pannexin-1 activation. On the
      other hand, this compound has no effects on cationic fluorescent dye uptake,
      apoptosis, and bleb formation, also dependent on P2X7R. Moreover, POM-1 can be
      considered an anti-inflammatory compound, because it prevents TNF-alpha and
      nitric oxide release from LPS-treated macrophages.

PMID- 29022165
TI  - A new approach to treat bone gaps after midfacial and zygomatic fractures with a
      collagen membrane.
AB  - PURPOSE: The aim of the study was to analyze the eligibility of resorbable
      collagen membrane in the treatment of midfacial fractures to prevent gap
      formation and subsequent cheek tissue retraction. MATERIAL AND METHODS: We
      included nine patients (six males, three females; mean age 51; range 20-73 years;
      mean bone gap size 8.03 * 13.12 mm) in a retrospective study design. The defect
      size was assessed by ultrasound. RESULTS: After a healing period of 4 to 55
      weeks, treatment resulted in a significant reduction of gap size (residual mean
      bone gap size 6.14 * 7.32 mm). CONCLUSIONS: Native resorbable collagen membrane
      is a promising tool to reduce the size of bony gap in midfacial defects.

PMID- 29022166
TI  - Patient views about polypharmacy medication review clinics run by clinical
      pharmacists in GP practices.
AB  - Background Polypharmacy can decrease medication adherence and increase the
      incidence of adverse drug reactions and drug-drug interactions, resulting in
      falls, hospitalisations and other complications especially in the elderly.
      Medication-related problems of polypharmacy can be prevented through patient
      centred medication reviews but research in this area has been completed largely
      without examining patients' viewpoints. Objective The aim was to investigate
      patient views about a clinical pharmacist-led patient-centred polypharmacy
      medication review service completed within 17 English GP practices with those >=
      75 years of age and prescribed >= 15 medications, during 415 consultations.
      Method A patient feedback questionnaire was constructed and face validated with
      two pharmacists then posted by a Clinical Commissioning Group pharmacist to all
      patients who had taken part in the service. Data from returned questionnaires
      were analysed using descriptive statistics and qualitative patient comments were
      analysed using thematic analysis. Results Of the 166 patients (40% response rate)
      who returned a feedback questionnaire 83% found the service helpful. Medication
      related concerns of 94% who had a concern beforehand were addressed, and 80%
      understood their medicines better after the review. Patients appreciated
      pharmacists' personal approach, advice and explanation. Conclusion Patients
      expressed broadly positive views about polypharmacy reviews by clinical
      pharmacists within GP practices.

PMID- 29022167
TI  - Stochastic evaluation of annual micropollutant loads and their uncertainties in
      separate storm sewers.
AB  - This article describes a stochastic method to calculate the annual pollutant
      loads and its application over several years at the outlet of three catchments
      drained by separate storm sewers. A stochastic methodology using Monte Carlo
      simulations is proposed for assessing annual pollutant load, as well as the
      associated uncertainties, from a few event sampling campaigns and/or continuous
      turbidity measurements (representative of the total suspended solids
      concentration (TSS)). Indeed, in the latter case, the proposed method takes into
      account the correlation between pollutants and TSS. The developed method was
      applied to data acquired within the French research project "INOGEV" (innovations
      for a sustainable management of urban water) at the outlet of three urban
      catchments drained by separate storm sewers. Ten or so event sampling campaigns
      for a large range of pollutants (46 pollutants and 2 conventional water quality
      parameters: TSS and total organic carbon (TOC)) are combined with hundreds of
      rainfall events for which, at least one among three continuously monitored
      parameters (rainfall intensity, flow rate, and turbidity) is available. Results
      obtained for the three catchments show that the annual pollutant loads can be
      estimated with uncertainties ranging from 10 to 60%, and the added value of
      turbidity monitoring for lowering the uncertainty is demonstrated. A low inter
      annual and inter-site variability of pollutant loads, for many of studied
      pollutants, is observed with respect to the estimated uncertainties, and can be
      explained mainly by annual precipitation.

PMID- 29022168
TI  - Vertebral heights and ratios are not only race-specific, but also gender- and
      region-specific: establishment of reference values for mainland Chinese.
AB  - : This study established gender-specific reference values in mainland Chinese
      (MC) and is important for quantitative morphometry for diagnosis and
      epidemiological study of osteoporotic vertebral compressive fracture. Comparisons
      of reference values among different racial populations are then performed to
      demonstrate the MC-specific characteristic. PURPOSE: Osteoporotic vertebral
      compressive fracture (OVCF) is a common complication of osteoporosis in the elder
      population. Clinical diagnosis and epidemiological study of OVCF often employ
      quantitative morphometry, which relies heavily on the comparison of patients'
      vertebral parameters to existing reference values derived from the normal
      population. Thus, reference values are crucial in clinical diagnosis. To our
      knowledge, this is the first study to establish reference values of the mainland
      Chinese (MC) for quantitative morphometry. METHODS: Vertebral heights including
      anterior (Ha), middle (Hm), posterior (Hp) heights, and predicted posterior
      height (pp) from T4 to L5 were obtained; and ratios of Ha/Hp, Hm/Hp and Hp/pp.
      were calculated from 585 MC (both female and male) for establishing reference
      values and subsequent comparisons with other studies. RESULTS: Vertebral heights
      increased progressively from T4 to L3 but then decreased in L4 and L5. Both
      genders showed similar ratios of vertebral dimensions, but male vertebrae were
      statistically larger than those of female (P < 0.01). Vertebral size of MC
      population was smaller than that of US and UK population, but was surprisingly
      larger than that of Hong Kong Chinese, although these two are commonly considered
      as one race. Data from different racial populations showed similar dimensional
      ratios in all vertebrae. CONCLUSIONS: We established gender-specific reference
      values for MC. Our results also indicated the necessity of establishing reference
      values that are not only race- and gender-specific, but also population- or
      region-specific for accurate quantitative morphometric assessment of OVCF.

PMID- 29022169
TI  - Consequences of hyperfiltration after significant renal ablation early in life.

PMID- 29022170
TI  - Modified staging system for pulmonary carcinoids on the basis of lung cancer TNM
      system.
AB  - BACKGROUND: Pulmonary carcinoids are being staged along the lines of lung cancer
      American Joint Committee on Cancer (AJCC) staging system. The current study
      evaluated the prognostic value of a modified staging system for patients with
      pulmonary carcinoid. PATIENTS AND METHODS: Surveillance, Epidemiology and End
      Results (SEER) database (2004-2014) was searched through SEER*Stat program.
      Through recursive partitioning analysis and subsequent decision tree formation,
      suggested stages were constructed. Overall survival analyses were performed
      through Kaplan-Meier analysis. The cancer-specific Cox regression hazard
      (adjusted for age, gender, race, sub-site and surgery) was calculated and
      pairwise comparisons of hazard ratios were conducted. RESULTS: A total of 6395
      pulmonary carcinoid patients were recruited in the period from 2004-2014.
      Pairwise hazard ratio comparisons among different AJCC 8th stages were conducted
      and all comparisons were non-significant except for stage IIB vs. stage IIIA and
      stage IIIA vs. stage IIIB. Pairwise hazard ratio comparisons among different
      modified staging system stages were conducted and all comparisons were
      significant except for stage III vs. stage IV. C-statistic (using death from
      pulmonary carcinoid as the dependent variable) for AJCC 8th staging system was:
      0.794 (SE 0.013; 95% CI 0.769-0.818); for AJCC 7th staging system was: 0.789 (SE
      0.013; 95% CI 0.764-0.815), while c-statistic for the modified staging system
      was: 0.802 (SE 0.012; 95% CI 0.778-0.827). CONCLUSION: The proposed modified
      staging system provided a simpler yet prognostically more relevant classification
      of pulmonary carcinoids compared to AJCC staging systems (both 7th and 8th
      editions).

PMID- 29022171
TI  - Debating social egg freezing: arguments from phases of life.
AB  - So-called "social egg freezing" allows a woman to retain the possibility of
      trying to have a child with her own oocytes later in life, even after having
      become infertile in the strict sense of the word (that is, infertile without
      assistance in reproduction).There is a debate about whether it is morally
      permissible at all, the extent to which it should be permitted legally or even
      supported, and whether it is ethically desirable. This paper contributes some
      thoughts to the issue of ethical desirability. More precisely it deals with the
      question of whether there is any valuable argument to be made on the basis of the
      idea of life phases and normative expectations related to them. So the question
      is: Is there a right time in life to have a child, and does this speak against or
      in favor of social freezing? This question is answered in three steps. First, I
      will give an overview of ethical arguments that are mostly put forward in favor
      or against the use of social egg freezing and show that and why the question of
      life phases should be taken into account. Second, I will sketch what I understand
      by phases of life, more precisely, what I understand by normatively
      conceptualized life stages, that are to be distinguished from other kinds of life
      phases, and how they relate to a good life. Third, I will present two arguments
      that rely on the idea of life stages and speak against social egg freezing.
      However, I will criticize them and instead show that from the perspective of life
      stages nothing speaks against using the technique within certain limits.

PMID- 29022173
TI  - Quantifying the potential export flows of used electronic products in Macau: a
      case study of PCs.
AB  - The used electronic product (UEP) has attracted the worldwide attentions because
      part of e-waste may be exported from developed countries to developing countries
      in the name of UEP. On the basis of large foreign trade data of electronic
      products (e-products), this study adopted the trade data approach (TDA) to
      quantify the potential exports of UEP in Macau, taking a case study of personal
      computers (PCs). The results show that the desktop mainframes, LCD monitors, and
      CRT monitors have more low-unit-value trades with higher trade volumes in the
      past 10 years, while the laptop and tablet PCs, as the newer technologies, owned
      the higher ratios of the high-unit-value trades. During the period of 2005-2015,
      the total mean exports for used laptop and tablet PCs, desktop mainframes, and
      LCD monitors were approximately 18,592, 79,957, and 43,177 units, respectively,
      while the possible export volume of used CRT monitors was higher, up to 430,098
      units in 2000-2010. Noticed that these potential export volumes could be the
      lower bound because not all used PCs may be shipped using the PC trade code. For
      all the four kinds of used PCs, the majority (61.6-98.82%) of the export volumes
      have gone to Hong Kong, followed by Mainland China and Taiwan. Since 2011, there
      was no CRT monitor export; however, the other kinds of used PC exports will still
      exist in Macau in the future. The outcomes are helpful to understand and manage
      the current export situations of used products in Macau, and can also provide a
      reference for other countries and regions.

PMID- 29022174
TI  - Challenges of Females with Autism: A Parental Perspective.
AB  - Most studies investigating the experiences and needs of individuals with ASD have
      largely focused on males. Hence, this study investigates parents' perspectives on
      the challenges that their daughters with ASD face. In total, 40 parents of 40
      females with autism (age range = 4-29 years; mean = 15.9) participated in the
      study. Five separate, 2-h long focus groups were conducted, with 7-10
      participants in each group. Field notes were analyzed using thematic analysis.
      Some of the issues parents discussed were similar to those experienced by males
      with ASD, such as challenges in social interactions. However, other issues
      discussed were of particular relevance to girls with ASD, including difficulties
      socializing with other girls, sex-specific puberty issues, barriers in accessing
      intervention and sexual vulnerability.

PMID- 29022176
TI  - Dexamethasone for chronic subdural hematoma: a systematic review and meta
      analysis.

PMID- 29022175
TI  - Dental anxiety and oral health-related quality of life in aggressive
      periodontitis patients.
AB  - OBJECTIVES: To measure dental anxiety levels and oral health-related qualities of
      life (OHRQoL) in patients with aggressive periodontitis (AgP) compared to
      controls and analyze their association with various demographic and clinical
      parameters. METHODS: Sixty consecutive patients with AgP were compared to 80 age-
      and sex-matched controls with no known history of periodontal disease. Collected
      data included demographics, smoking habits, numerical rating scale (NRS), Corah's
      Dental Anxiety Scale (DAS) and Oral Health Impact Profile-14 (OHIP-14), DMFT
      index (Decayed, Missing and Filled Teeth), Plaque Index (PI), probing depth (PD),
      bleeding on probing (BOP), and radiographic bone loss. RESULTS: AgP patients
      exhibited statistically significant higher scores in the DAS total as well as sub
      scores, except from DAS 1st question. Compared to the control group, AgP patients
      exhibited worse OHIP-14 global as well as in all individual OHIP-14 domains
      scores. Among both AgP and control patients, the physical pain domain was where
      the highest impact was recorded, while the lowest impact was recorded in the
      functional limitation domain. CONCLUSIONS: AgP patients were positively
      associated with higher levels of dental anxiety and worse OHRQoL. Self-perception
      of dental anxiety and OHRQoL should be regarded as an integral element in routine
      diagnostic work-up process of periodontal diseases. STATEMENT OF CLINICAL
      RELEVANCE: Aggressive periodontitis (AgP) patients exhibited higher dental
      anxiety levels and worse oral health-related quality of life (OHRQoL) compared to
      controls. Professionals should design strategies that will cope with the dental
      anxiety associated with the treatment and prevent decreases in OHRQoL.

PMID- 29022177
TI  - Association between dietary zinc intake and mortality among Chinese adults:
      findings from 10-year follow-up in the Jiangsu Nutrition Study.
AB  - PURPOSE: Population studies of the association between zinc intake and mortality
      yield inconsistent findings. Using data from Jiangsu Nutrition Study, we aimed to
      assess the association between zinc intake and mortality among Chinese adults.
      METHODS: We prospectively studied 2832 adults aged 20 years and older with a mean
      follow-up of 9.8 years. At baseline, food intake was measured by 3-day weighed
      food record (WFR) between September and December in 2002. Death occurrence was
      assessed in 2012 during a household visit as well as by data linkage with the
      regional death registry. Hazard ratios (HRs) and 95% CI were calculated using
      competing risks regression (CVD and cancer mortality) and Cox proportional
      hazards analysis (all-cause mortality). RESULTS: During 27,742 person-years of
      follow-up, there were 184 deaths [63 cancer deaths and 70 cardiovascular disease
      (CVD) deaths]. Dietary zinc to energy ratio was positively associated with cancer
      and all-cause mortality. Across quartiles of the zinc to energy ratio from low to
      high, the HR (95% CI) for all-cause mortality was 1.00, 1.80 (95% CI 1.10-2.95),
      1.55 (95% CI 0.96-2.50), and 1.85 (95% CI 1.11-3.07), respectively. Comparing the
      extreme quartiles of the zinc to energy ratio, the HR for cancer mortality was
      2.28 (95% CI 1.03-5.04). CONCLUSION: Zinc intake was positively related to all
      cause mortality and cancer mortality.

PMID- 29022178
TI  - Interactive effects of PAHs with different rings and As on their uptake,
      transportation, and localization in As hyperaccumulator.
AB  - In order to illuminate the mechanism of the interaction of polycyclic aromatic
      hydrocarbon (PAH) with different benzene rings and arsenic (As) in As
      hyperaccumulator, Pteris vittata L., the uptakes of PAHs were investigated using
      hydroponics simulation and localizations of PAHs in the plant were determined
      using two-photon laser scanning confocal microscopy (TPLSCM). The results showed
      that the total As concentration in different parts of P. vittata decreased in the
      presence of PAHs with increased numbers of benzene rings: 38.0-47.4% for
      benzo(a)pyrene (BaP, five rings), 20.5-35.9% for pyrene (PYR, four rings), and
      13.7-16.6% for fluorine (FLU, three rings). BaP and PYR concentrations increased,
      while FLU concentration decreased in the presence of As. The results of TPLSCM
      revealed that PAHs distributed in epidermal cells of roots, xylem, and
      endothelial cells of rachis, epidermis, and stomatal cells of pinnae; however,
      the fluorescence intensity of BaP and PYR were higher than FLU significantly in
      plant. This study provided important basis to further research on interactive
      effects of PAHs and As in the P. vittata. These findings were important to
      understand the mechanisms of PAH and As translocation and distribution by P.
      vittata.

PMID- 29022180
TI  - Duration of trastuzumab in HER2-positive metastatic breast cancer after complete
      remission: still debatable issue?

PMID- 29022179
TI  - First identification of porcine parvovirus 7 in China.
AB  - Porcine parvovirus (PPV) are small, non-enveloped and single-stranded DNA
      viruses, taxonomically classifiable within the family Parvoviridae. Seven PPV
      genotypes (PPV1 to PPV7) have been identified to date. PPV7, the most recently
      discovered PPV genotype, was first reported in US pigs in 2016. To explore PPV7
      status in Chinese pig populations a total of 64 serum samples collected from two
      commercial farms in Guangdong province in 2014 were analyzed. PPV7 DNA was
      detected in 32.8% (21/64) of tested samples. On the porcine circovirus type 2
      (PCV2) positive farm, the prevalence rate of PPV7 was 65.5% (19/29) which was
      significantly higher than that on the PCV2 negative farm (2/35, 5.7%), indicating
      a possible association between PCV2 and PPV7 infections. The sequences of three
      PPV7 strains were determined. Phylogenetic analysis revealed that the identified
      PPV7 strains circulating in China shared 98.7%-99.7% nucleotide homology with the
      US strain. Further sequence comparison analysis indicated that GD-2014-2 and GD
      2014-3 possess a consecutive 9-nt deletion in the VP gene. This is the first
      report of the existence of PPV7 in China and this finding will strengthen
      understanding of the epidemiology of porcine parvovirus in Chinese pigs.

PMID- 29022181
TI  - Occurrence of selected elements (Ti, Sr, Ba, V, Ga, Sn, Tl, and Sb) in deposited
      dust and human hair samples: implications for human health in Pakistan.
AB  - The current study determined, for the first time, the levels of titanium (Ti),
      strontium (Sr), barium (Ba), vanadium (V), gallium (Ga), tin (Sn), thallium (Tl),
      and antinomy (Sb), in deposited dust, and human hair collected from general
      population of different geographical areas of Pakistan. All the samples were
      prepared by microwave digestion and measured by ICP-MS. The results showed that
      on deposited dust samples, the detected elements followed the descending trend
      as: Ti > Sr > Ba > V > Ga > Sn > Tl > Sb similar to the upper continental crust.
      The deposited dust samples from low elevation areas exhibited highest levels of
      all studied elements (except antimony which was higher in soil samples from
      mountainous areas), followed by rive plains, mountainous areas, and highland
      valleys. In contrast, on human hair samples, the elements followed the descending
      trend as: Sr > Ba > Ti > Ga > V > Sn > Sb > Tl respectively. Ba, Ga, and V
      concentrations were higher in soil samples from lower elevation Indus plain, and
      Sr, Tl, Sb, and Ti were higher in samples from mountainous areas. The
      bioaccumulation trend of all studied elements was in descending order as follows:
      Sb, Ga, Sn, Ba, Sr, Ti, V, Tl, respectively. Principal component analysis (PCA)
      and correlation matrix evidenced both geological influences and anthropogenic
      activities as potential sources of these studied elements. On the other hand, the
      risk estimation (HI > 1) concluded that population were at higher health risk
      (non-carcinogenic) for Ga and Ti. All other studied rare elements were within
      safe limit for humans from all zones.

PMID- 29022182
TI  - Coexistent rheumatoid arthritis and gout: a case series and review of the
      literature.
AB  - Since 1964 to present, there have been more than 33 cases of concomitant
      rheumatoid arthritis (RA) and gout reported in the literature. The objective of
      this study is to present a case series of patients with coexistent rheumatoid
      arthritis and gout and to provide a review of the literature. A retrospective
      review of a rheumatology patient database at the University of Alberta was
      performed (2004-2017). Patient charts were reviewed and the 1987 ARA Revised
      Classification Criteria for RA and 1977 ARA Classification Criteria for gout were
      applied to each patient. For gout, positive monosodium urate crystals on synovial
      fluid analysis, synovial/node biopsy, or positive dual-energy CT-gout protocol
      were used to satisfy the diagnosis of gout if available. Thirteen patients were
      identified with both RA and gout (nine men and four women). The mean age was
      68.6, while the mean age at the onset of first disease was 55.3 and onset of
      second disease was 64.4. Eight patients were initially diagnosed with RA and
      subsequently developed gout, while five patients were first diagnosed with gout
      and subsequently developed RA. Standard radiographs showed findings
      characteristic of RA and gout in affected joints. In joints affected by both
      diseases, the gout findings predominated and the RA changes were milder.
      Rheumatoid arthritis and gout do coexist in the same patient, contrary to popular
      belief. Understanding that both conditions can occur concomitantly is necessary
      for clinical awareness, especially in patients with polyarticular disease that is
      difficult to treat.

PMID- 29022184
TI  - Effects of Ketoconazole on the Pharmacokinetics of Mifepristone, a Competitive
      Glucocorticoid Receptor Antagonist, in Healthy Men.
AB  - INTRODUCTION: Mifepristone, a competitive glucocorticoid receptor antagonist
      approved for Cushing syndrome, and ketoconazole, an antifungal and
      steroidogenesis inhibitor, are both inhibitors of and substrates for cytochrome
      P450 (CYP3A4). This study evaluated the pharmacokinetic effects of concomitant
      ketoconazole, a strong CYP3A4 inhibitor, on mifepristone. METHODS: In an open
      label, two-period, single-center study, healthy adult men received mifepristone
      600 mg orally daily for 12 days (period 1) followed by mifepristone 600 mg daily
      plus ketoconazole 200 mg orally twice daily for 5 days (period 2). Serial
      pharmacokinetic blood samples were collected predose and over 24 h postdose on
      days 12 (period 1) and 17 (period 2). A cross-study comparison (using data on
      file) further examined whether systemic exposure to mifepristone plus
      ketoconazole exceeded the exposure following mifepristone 1200 mg orally
      administered for 7 days. RESULTS: Sixteen subjects were enrolled and 14 completed
      the study. Concomitant administration with ketoconazole increased the systemic
      exposure to mifepristone, based on geometric least squares mean ratios, by 28%
      for C max and 38% for AUC0-24. This increase was 85% and 87% of the exposure
      observed following mifepristone's highest label dose of 1200 mg/day for C max and
      AUC0-24, respectively. Adverse events (AEs) were reported in 56.3% (9/16) of
      subjects during administration of mifepristone alone and in 57.1% (8/14) during
      combination with ketoconazole. No serious AEs were reported. CONCLUSION: Systemic
      exposure to mifepristone increased following multiple doses of mifepristone 600
      mg daily plus ketoconazole 200 mg twice daily. Little to no increase in AEs
      occurred. Dose adjustment of mifepristone may be needed when given with
      ketoconazole. FUNDING: Corcept Therapeutics.

PMID- 29022186
TI  - Response distortion on personality tests in applicants: comparing high-stakes to
      low-stakes medical settings.
AB  - The current study examined the degree to which applicants applying for medical
      internships distort their responses to personality tests and assessed whether
      this response distortion led to reduced predictive validity. The applicant sample
      (n = 530) completed the NEO Personality Inventory whilst applying for one of 60
      positions as first-year post-graduate medical interns. Predictive validity was
      assessed using university grades, averaged over the entire medical degree.
      Applicant responses for the Big Five (i.e., neuroticism, extraversion, openness,
      conscientiousness, and agreeableness) and 30 facets of personality were compared
      to a range of normative samples where personality was measured in standard
      research settings including medical students, role model physicians, current
      interns, and standard young-adult test norms. Applicants had substantially higher
      scores on conscientiousness, openness, agreeableness, and extraversion and lower
      scores on neuroticism with an average absolute standardized difference of 1.03,
      when averaged over the normative samples. While current interns, medical
      students, and especially role model physicians do show a more socially desirable
      personality profile than standard test norms, applicants provided responses that
      were substantially more socially desirable. Of the Big Five, conscientiousness
      was the strongest predictor of academic performance in both applicants (r = .11)
      and medical students (r = .21). Findings suggest that applicants engage in
      substantial response distortion, and that the predictive validity of personality
      is modest and may be reduced in an applicant setting.

PMID- 29022183
TI  - In search of a comprehensible set of endpoints for the routine monitoring of
      neurotoxicity in vertebrates: sensory perception and nerve transmission in
      zebrafish (Danio rerio) embryos.
AB  - In order to develop a test battery based on a variety of neurological systems in
      fish, three sensory systems (vision, olfaction, and lateral line) as well as
      nerve transmission (acetylcholine esterase) were analyzed in zebrafish (Danio
      rerio) embryos with respect to their suitability as a model for the screening of
      neurotoxic trace substances in aquatic ecosystems. As a selection of known or
      putative neurotoxic compounds, amidotrizoic acid, caffeine, cypermethrin,
      dichlorvos, 2,4-dinitrotoluene, 2,4-dichlorophenol, 4-nonylphenol,
      perfluorooctanoic acid, and perfluorooctane sulfonic acid were tested in the fish
      embryo test (OECD test guideline 236) to determine EC10 values, which were then
      used as maximum test concentration in subsequent neurotoxicity tests. Whereas
      inhibition of acetylcholinesterase was investigated biochemically both in vivo
      and in vitro (ex vivo), the sensory organs were studied in vivo by means of
      fluorescence microscopy and histopathology in 72- or 96-h-old zebrafish embryos,
      which are not regarded as protected developmental stages in Europe and thus - at
      least de jure - represent alternative test methods. Various steps of optimization
      allowed this neurotoxicity battery to identify neurotoxic potentials for five out
      of the nine compounds: Cypermethrin and dichlorvos could be shown to specifically
      modulate acetylcholinesterase activity; dichlorvos, 2,4-dichlorophenol, 4
      nonylphenol, and perfluorooctane sulfonic acid led to a degeneration of
      neuromasts, whereas both vision and olfaction proved quite resistant to
      concentrations <= EC10 of all of the model neurotoxicants tested. Comparison of
      neurotoxic effects on acetylcholinesterase activity following in vivo and in
      vitro (ex vivo) exposure to cypermethrin provided hints to a specific enzyme
      modulating activity of pyrethroid compounds. Enhancement of the neuromast assay
      by applying a simultaneous double-staining procedure and implementing a 4-scale
      scoring system (Stengel et al. 2017) led to reduced variability of results and
      better statistical resolution and allowed to differentiate location-dependent
      effects in single neuromasts. Since acetylcholinesterase inhibition and neuromast
      degeneration can be analyzed in 72- and 96-h-old zebrafish embryos exposed to
      neurotoxicants according to the standard protocol of the fish embryo toxicity
      test (OECD TG 236), the fish embryo toxicity test can be enhanced to serve as a
      sensitive neurotoxicity screening test in non-protected stages of vertebrates.

PMID- 29022187
TI  - Assessing the Role of Reversible Contraceptives in the Health Care of Women as it
      Pertains to Cancer Prevention.
AB  - The use of effective and reversible contraception is characterized by many non
      contraceptive benefits distinct from its ability to prevent pregnancy. Notably,
      the use of hormonal and non-hormonal birth control methods is known to impact the
      risk for developing certain female genital cancers as well as breast and colon
      cancers. We present here the current understanding of the role of effective and
      reversible contraceptives in the prevention and development of female genital
      cancers along with breast and colon cancers. Despite ongoing but unsubstantiated
      concerns regarding the use of hormonal and intrauterine contraceptives for a
      variety of clinical outcomes including cancer, contraceptive use in high- and low
      risk reproductive-aged women remains an important part of cancer risk reduction
      for many malignancies.

PMID- 29022188
TI  - Swimming in a tsunami of change.

PMID- 29022185
TI  - Biological/pathological functions of the CXCL12/CXCR4/CXCR7 axes in the
      pathogenesis of bladder cancer.
AB  - CXC chemokine ligand 12 (CXCL12) is an important member of the CXC subfamily of
      chemokines, and has been extensively studied in various human body organs and
      systems, both in physiological and clinical states. Ligation of CXCL12 to CXCR4
      and CXCR7 as its receptors on peripheral immune cells gives rise to pleiotropic
      activities. CXCL12 itself is a highly effective chemoattractant which
      conservatively attracts lymphocytes and monocytes, whereas there exists no
      evidence to show attraction for neutrophils. CXCL12 regulates inflammation, neo
      vascularization, metastasis, and tumor growth, phenomena which are all pivotally
      involved in cancer development and further metastasis. Generation and secretion
      of CXCL12 by stromal cells facilitate attraction of cancer cells, acting through
      its cognate receptor, CXCR4, which is expressed by both hematopoietic and non
      hematopoietic tumor cells. CXCR4 stimulates tumor progression by different
      mechanisms and is required for metastatic spread to organs where CXCL12 is
      expressed, thereby allowing tumor cells to access cellular niches, such as the
      marrow, which favor tumor cell survival and proliferation. It has also been
      demonstrated that CXCL12 binds to another seven-transmembrane G-protein receptor
      or G-protein-coupled receptor, namely CXCR7. These studies indicated critical
      roles for CXCR4 and CXCR7 mediation of tumor metastasis in several types of
      cancers, suggesting their contributions as biomarkers of tumor behavior as well
      as potential therapeutic targets. Furthermore, CXCL12 itself has the capability
      to stimulate survival and growth of neoplastic cells in a paracrine fashion.
      CXCL12 is a supportive chemokine for tumor neovascularization via attracting
      endothelial cells to the tumor microenvironment. It has been suggested that
      elevated protein and mRNA levels of CXCL12/CXCR4/CXCR7 are associated with human
      bladder cancer (BC). Taken together, mounting evidence suggests a role for CXCR4,
      CXCR7, and their ligand CXCL12 during the genesis of BC and its further
      development. However, a better understanding is still required before exploring
      CXCL12/CXCR4/CXCR7 targeting in the clinic.

PMID- 29022189
TI  - Knowledge, perceptions, and practice of ecopharmacovigilance among pharmacy
      professionals in China.
AB  - Ecopharmacovigilance (EPV) is now a well-accepted critical component for the
      control of potential environmental risk posed by pharmaceutical residues. And
      improving the knowledge and perceptions about EPV, especially among pharmacy
      professionals, is the first step towards addressing the environmental impact of
      pharmaceuticals. This cross-sectional study was conducted to assess the
      knowledge, perceptions, and practice on EPV using a validated self-administered
      questionnaire delivered to a sample of 120 pharmacy professionals in Hubei
      Province, China. And 107 usable survey instruments were acquired. The mean score
      for knowledge about EPV was 3.85 out of a total of 10. The pharmacy
      professionals' overall perceptions of EPV and pharmaceutical pollution in
      environment were positive. But of the 107 respondents, 45 (42%) stated that they
      had not participated in any EPV measure. In addition, none had received training
      on EPV, and only 25 (23%) respondents had read the literature on EPV. In response
      to the question about the major perceived barrier to the effective implementation
      of EPV in China, 45 (42%) respondents chose the answer "poor awareness of EPV."
      These data suggests most pharmacy professionals in China had a positive attitude
      but lack of knowledge and practices towards EPV. Therefore, more should be done
      to enhance pharmacy professionals' knowledge on EPV.

PMID- 29022190
TI  - In vivo study of a bioactive nanoparticle-gelatin composite scaffold for bone
      defect repair in rabbits.
AB  - The purpose is to study the in vivo bioactivity of this scaffold and verify its
      ability to simulate the characteristics of cancellous bone. Twenty-four adult New
      Zealand white rabbits were divided into three groups. Bone defects above the
      femoral condylar of both sides were created. A newly designed bioactive
      nanoparticle-gelatin composite scaffold was implanted to the experimental side,
      while the control side was left without implantation. The repair of bone defect
      was monitored by X-ray examination, gross observation, Micro-CT examination and
      histological observation of the area of bone defect 4, 8 and 12 weeks after
      surgery. There was void of new bone tissue in medullary cavity in the bone defect
      area of the control side. In the experimental side, the composite scaffold
      displayed excellent biodegradability, bioactivity and cyto-compatibility. With
      the time laps, new bone tissue grew from the edge to center as revealed by both
      Micro-CT image and staining biopsy, which complies with the "creeping
      substitution" process. The mechanical properties of the newly designed bioactive
      nanoparticle-gelatin composite scaffold and the 3-D structure of new bone tissue
      are comparable to the surrounding cancellous bones. This newly developed
      bioactive nanoparticle-gelatin composite scaffold possesses good biocompatibility
      and in vivo osteogenic capability for bone defect repair. It may be a promising
      artificial bone grafts.

PMID- 29022191
TI  - The association between subjectively impaired sleep and symptoms of depression
      and anxiety in a frail elderly population.
AB  - BACKGROUND: Most previous studies showed an association between sleep impairment
      in the elderly and symptoms of depression and anxiety. Majority of these studies
      were conducted in "strong", community-dwelling elderly. AIM: To assess the
      association between subjective sleep impairment and its affective disturbances
      among frail elderly patients. METHODS: The retrospective study included patients
      65 years old and above. Data included socio-demographic characteristics, the mini
      mental state examination, the short anxiety screening test, the 15-item Geriatric
      Depression Scale, and the Patient Health Questionnaire. The patients were asked
      about sleep complaints. RESULTS: The study population consisted of 496 patients.
      The mean age was 83.7 +/- 6.2 years, and only 7 (1.4%) did not report any sleep
      disturbance. After adjustment, depression symptoms were associated only with
      decreased overall sleep satisfaction (OR 2.62, 95% CI 1.18-5.81), while anxiety
      symptoms were associated with decreased overall sleep satisfaction (OR 3.17, 96%
      CI 1.71-5.88), difficulty falling asleep (OR 3.58, 95% CI 1.96-6.52), waking up
      during the night (OR 3.16, 95% CI 1.63-6.1), morning weakness (OR 2.68, 95% CI
      1.44-5.0) and daytime drowsiness (OR 2.39, 95% CI 1.21-4.69). DISCUSSION: Sleep
      impairment is very prevalent among frail elderly and associated much more with
      anxiety than with depression. CONCLUSION: The findings of the present study
      provide further evidence for the importance in taking a detailed history of sleep
      habits during the course of the geriatric assessment in frail elderly patients.

PMID- 29022192
TI  - A positive circuit of VEGF increases Glut-1 expression by increasing HIF-1alpha
      gene expression in human retinal endothelial cells.
AB  - Treatment of human retinal microvascular endothelial cells (HRMECs) with vascular
      endothelial growth factor 165 (VEGF165) increased hypoxia-inducible factor 1alpha
      (HIF-1alpha), VEGF, and glucose transporter 1 (Glut-1) mRNA expression and Glut-1
      protein localization to the membrane. In contrast, treatment of human retinal
      pigment epithelium cells with VEGF165 did not induce HIF-1alpha, VEGF, and Glut-1
      gene expression. Microvascular endothelial cells are surrounded by astrocytic end
      feet in the retina. Astrocyte-derived A-kinase anchor protein 12 overexpression
      during hypoxia downregulated VEGF secretion, and this conditioned medium reduced
      VEGF and Glut-1 expression in HRMECs, suggesting that communications between
      astrocytes and endothelial cells may be the determinants of the blood vessel
      network. In HRMECs, HIF-1alpha small interfering RNA transfection blocked the
      VEGF165-mediated increase in VEGF and Glut-1 gene expression. Inhibition of
      protein kinase C (PKC) with inhibitor GF109203X or with a small interfering RNA
      targeting PKCzeta attenuated the VEGF165-induced Glut-1 protein expression and
      VEGF and Glut-1 mRNA expression. In addition, results of an immunoprecipitation
      assay imply an interaction between VEGF receptor 2 (VEGFR2) and PKCzeta in
      HRMECs. Therefore, VEGF secretion by hypoxic astrocytes may upregulate HIF-1alpha
      gene expression, inducing VEGF and Glut-1 expression via the VEGFR2-PKCzeta axis
      in HRMECs.

PMID- 29022193
TI  - Development of a modular vapor intrusion model with variably saturated and non
      isothermal vadose zone.
AB  - Human health risk assessment at hydrocarbon-contaminated sites requires a
      critical evaluation of the exposure pathways of volatile organic compounds
      including assessments of vapor exposure in indoor air. Although there are a
      number of vapor intrusion models (VIM) currently available, they rarely reproduce
      actual properties of soils in the vadose zone. At best, users of such models
      assume averaged parameters for the vadose zone based on information generated
      elsewhere. The objective of this study was to develop a one-dimensional steady
      state VIM, indoorCARETM model, that considers vertical spatial variations of the
      degree of saturation (or effective air-filled porosity) and temperature of the
      vadose zone. The indoorCARETM model was developed using a quasi-analytical
      equation that (1) solves the coupled equations governing soil-water movement
      driven by pressure head and a soil heat transport module describing conduction of
      heat and (2) provides a VIM that accommodates various types of conceptual site
      model (CSM) scenarios. The indoorCARETM model is applicable to both chlorinated
      hydrocarbon and petroleum hydrocarbon (PHC) contaminated sites. The model
      incorporates biodegradations of PHCs at a range of CSM scenarios. The results
      demonstrate that predictions of indoor vapor concentrations made with the
      indoorCARETM model are close to those of the J&E and BioVapor models under
      homogeneous vadose zone conditions. The newly developed model under heterogeneous
      vadose zone conditions demonstrated improved predictions of indoor vapor
      concentrations. The research study presented a more accurate and more realistic
      way to evaluate potential human health risks associated with the soil-vapor-to
      indoor-air pathways.

PMID- 29022195
TI  - High LC3/Beclin Expression Correlates with Poor Survival in Glioma: a Definitive
      Role for Autophagy as Evidenced by In Vitro Autophagic Flux.
AB  - Recent studies suggest the role of autophagy, an evolutionarily conserved
      catabolic process, in determining the response of gliomas to treatment either
      positively or negatively. The study attempts to characterize autophagy in low and
      high-grade glioma by investigating the autophagic flux and clinical significance
      of autophagy proteins (LC3 and beclin 1) in a group of glioma patients. We
      evaluated the expression of autophagic markers in resected specimens of low-grade
      glioma (LGG) and high-grade glioma (HGG) tissues, by immunohistochemistry and
      Western blotting. Our results show that expression of autophagy proteins were
      more prominent in HGG than in LGG. Increased level of autophagic proteins in HGG
      can be due to an increased rate of autophagy or can be because of blockage in the
      final degradation step of autophagy (defective autophagy). To distinguish these
      possibilities, the autophagic flux assay which helps to determine the rate of
      degradation/synthesis of autophagic proteins (LC3-II and p62) over a period of
      time by blocking the final degradation step of autophagy using bafilomycin A1 was
      used . The assessment of autophagic flux in ex vivo culture of primary glioma
      cells revealed for the first time increased turnover of autophagy in high grade
      compared to low grade-glioma. Though autophagic markers were reduced in LGG,
      functionally autophagy was non defective in both grades of glioma. We then
      investigated whether autophagy in gliomas is regulated by nutrient sensing
      pathways including mTOR and promote cell survival by providing an alternate
      energy source in response to metabolic stress. The results depicted that the role
      of autophagy during stress varies with tissue and has a negative correlation with
      mTOR substrate phosphorylation. We also evaluated the expression of LC3 and
      beclin 1 with progression free survival (PFS) using Kaplan-Meier survival
      analysis and have found that patients with low LC3/beclin 1 expression had better
      PFS than those with high expression of LC3/beclin 1 in their tumors. Together, we
      provide evidence that autophagy is non-defective in glioma and also show that
      high LC3/beclin 1 expression correlates with poor PFS in both LGG and HGG.

PMID- 29022194
TI  - Potential for cometabolic biodegradation of 1,4-dioxane in aquifers with methane
      or ethane as primary substrates.
AB  - The objective of this research was to evaluate the potential for two gases,
      methane and ethane, to stimulate the biological degradation of 1,4-dioxane (1,4
      D) in groundwater aquifers via aerobic cometabolism. Experiments with aquifer
      microcosms, enrichment cultures from aquifers, mesophilic pure cultures, and
      purified enzyme (soluble methane monooxygenase; sMMO) were conducted. During an
      aquifer microcosm study, ethane was observed to stimulate the aerobic
      biodegradation of 1,4-D. An ethane-oxidizing enrichment culture from these
      samples, and a pure culture capable of growing on ethane (Mycobacterium sphagni
      ENV482) that was isolated from a different aquifer also biodegraded 1,4-D. Unlike
      ethane, methane was not observed to appreciably stimulate the biodegradation of
      1,4-D in aquifer microcosms or in methane-oxidizing mixed cultures enriched from
      two different aquifers. Three different pure cultures of mesophilic methanotrophs
      also did not degrade 1,4-D, although each rapidly oxidized 1,1,2-trichloroethene
      (TCE). Subsequent studies showed that 1,4-D is not a substrate for purified sMMO
      enzyme from Methylosinus trichosporium OB3b, at least not at the concentrations
      evaluated, which significantly exceeded those typically observed at contaminated
      sites. Thus, our data indicate that ethane, which is a common daughter product of
      the biotic or abiotic reductive dechlorination of chlorinated ethanes and
      ethenes, may serve as a substrate to enhance 1,4-D degradation in aquifers,
      particularly in zones where these products mix with aerobic groundwater. It may
      also be possible to stimulate 1,4-D biodegradation in an aerobic aquifer through
      addition of ethane gas. Conversely, our results suggest that methane may have
      limited importance in natural attenuation or for enhancing biodegradation of 1,4
      D in groundwater environments.

PMID- 29022196
TI  - Advances of radiation sterilisation in tissue banking.
AB  - Under the auspices of the IAEA tissue banking programme on "Radiation
      Sterilisation of Tissue Graft" conducted from 1985 to 2004, many scientists and
      surgeons were involved in various regional research and development (R&D)
      projects mainly in dealing with radiation dose selection, radiation effects on
      human tissues and quality system in radiation sterilisation. New findings on
      radiation effects, tissue processing and preservation were shared during the
      regional and interregional meetings and workshops. Many tissue banks started to
      use radiation (25 kGy) to sterilize tissue grafts for tissue safety and efficacy
      and still continue to use it. The IAEA Code of Practice for Radiation
      Sterilization of Tissues Allografts developed in 2007 offered simpler methods to
      conduct radiation dose setting and dose validation experiments for tissue grafts.
      Advances in dose selection and dose mapping are continued under the quality
      management system when banks need to be certified to continue their operation.
      The combination of good tissue processing and preservation as well as good
      radiation practice will ensure the tissue products are properly sterilised thus
      safe and of high quality. Experience in meeting challenges in using radiation
      sterilisation and achievements reported by the tissue bankers are shared here.

PMID- 29022197
TI  - A Case of Recalcitrant Psoriatic Arthritis to TNF Inhibitors Improved After
      Administration of Secukinumab, an IL-17A Inhibitor.
AB  - Psoriatic arthritis (PsA) is a unique inflammatory arthritis due to the fact that
      patients have to deal not only with pain but also with their skin appearance,
      which may have a detrimental effect on their everyday lives and psychology.
      Treating a patient with PsA, improving both the musculoskeletal and skin symptoms
      is a challenge for the clinical rheumatologist. In this case, we present a
      patient of recalcitrant PsA to tumor necrosis factor inhibitors (TNFi) who had an
      exceptional improvement after administration of the interleukin-17A inhibitor (IL
      17Ai) secukinumab.

PMID- 29022198
TI  - Gene Disruption in Scedosporium aurantiacum: Proof of Concept with the Disruption
      of SODC Gene Encoding a Cytosolic Cu,Zn-Superoxide Dismutase.
AB  - Scedosporium species are opportunistic pathogens responsible for a large variety
      of infections in humans. An increasing occurrence was observed in patients with
      underlying conditions such as immunosuppression or cystic fibrosis. Indeed, the
      genus Scedosporium ranks the second among the filamentous fungi colonizing the
      respiratory tracts of the CF patients. To date, there is very scarce information
      on the pathogenic mechanisms, at least in part because of the limited genetic
      tools available. In the present study, we successfully developed an efficient
      transformation and targeted gene disruption approach on the species Scedosporium
      aurantiacum. The disruption cassette was constructed using double-joint PCR
      procedure, and resistance to hygromycin B as the selection marker. This proof of
      concept was performed on the functional gene SODC encoding the Cu,Zn-superoxide
      dismutase. Disruption of the SODC gene improved susceptibility of the fungus to
      oxidative stress. This technical advance should open new research areas and help
      to better understand the biology of Scedosporium species.

PMID- 29022199
TI  - Injuries in Children with Autism Spectrum Disorder: Study to Explore Early
      Development (SEED).
AB  - This study examined caregiver-reported medically-attended injuries among 30-68
      month old children with autism spectrum disorder (ASD) compared to general
      population (POP) and non-ASD developmental disorders (DD) controls in the Study
      to Explore Early Development. Injuries were common in ASD cases (32.3%) as well
      as POP (30.2%) and DD (27.8%) controls; most resulted in an emergency visit or
      hospitalization. After accounting for sociodemographic, health, IQ and behavior
      differences, odds of injury in ASD cases were significantly higher than DD
      controls but similar to POP controls. Attention problems mediated the
      relationships. Clinicians caring for children with both ASD and attention
      problems should consider providing targeted safety advice. Differences in injury
      risk between children with ASD vs. other developmental disorders need further
      study.

PMID- 29022200
TI  - High Expression of the Mitophagy-Related Protein Pink1 is Associated with a Poor
      Response to Chemotherapy and a Poor Prognosis for Patients Treated with
      Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma.
AB  - BACKGROUND: Autophagy plays a major role in cellular homeostasis and is
      implicated in cancer progression. Damaged mitochondria are scavenged and
      eliminated by mitochondrial autophagy, referred to as mitophagy, which can
      promote cancer cell survival. This study investigated the expression and effects
      of the autophagy-related protein LC3 and the mitophagy-related protein Pink1 in
      human esophageal squamous cell carcinoma (ESCC). METHODS: Both LC3 and Pink1 were
      analyzed by immunohistochemistry in tissues from 217 ESCC patients, including 159
      patients undergoing neoadjuvant chemotherapy. The relationships between LC3 and
      Pink1 expression and various clinicopathologic factors were determined. In vitro
      assays were performed to assess the role of LC3 and Pink1 in ESCC
      chemoresistance. RESULTS: High LC3 expression was observed in 47.9% and high
      Pink1 expression in 48.4% of the ESCC patients. Pink1 expression was
      significantly higher in patients who underwent chemotherapy than in patients who
      did not (p = 0.032). High LC3 and Pink1 expression was significantly correlated
      with poor response to chemotherapy (p = 0.004 and p < 0.001, respectively), and
      high expression of Pink1, but not LC3, was significantly correlated with a poor
      prognosis for patients treated with preoperative chemotherapy (p = 0.007).
      Multivariate analysis identified Pink1 expression as an independent prognostic
      factor (p = 0.042). In vitro assays demonstrated that LC3-II and Pink1 expression
      increased after chemotherapeutic treatment in the ESCC cell line, and inhibition
      of autophagy and mitophagy using chloroquine and siPink1, respectively, restored
      chemosensitivity. CONCLUSIONS: High expression of Pink1 is associated with
      chemoresistance and a poor prognosis for ESCC patients undergoing neoadjuvant
      chemotherapy.

PMID- 29022202
TI  - Clove oil induces anaesthesia and blunts muscle contraction power in three Amazon
      fish species.
AB  - Clove oil is used as an anaesthetic for many species of fish worldwide; however,
      relatively few studies have assessed its effectiveness on Amazon fish species and
      no compelling evidence has ever been reported on the relaxant properties of this
      oil for skeletal muscle of fish. Thus, the objective of this study was to
      evaluate the latencies to deep anaesthesia and recovery, along with the
      myorelaxant effect of clove oil on three Amazon fish species: cardinal tetra,
      Paracheirodon axelrodi, banded cichlid, Heros severus and angelfish, Pterophyllum
      scalare, submitted to short-term anaesthetic baths. Fish were assayed in three
      groups of 60 fish each and individually anaesthetized in a completely randomized
      design with six clove oil concentrations using 10 fish/species/concentration.
      Electromyographic recordings from dorsal muscle were performed during stages of
      induction and recovery in which nine fish/species/stage were used. Deep
      anaesthesia was attained for all concentrations tested, and no mortalities were
      observed throughout the experiments and after a 48-h observation period.
      Concentration of 90 MUL L-1 and above promoted fast deep anaesthesia (< 3 min)
      and calm recovery in angelfish and cardinal tetra, whereas the concentration of
      60 MUL L-1 sufficed to quickly anaesthetize banded cichlid. Times to full
      recovery were not significantly contrasting among species and occurred within
      appropriate time threshold (< 5 min). Clove oil exerted a conspicuous depression
      of muscle contraction power, and therefore can be effectively used as a muscle
      relaxant agent for P. scalare, P. axelrodi, H. severus and potentially, for other
      fish species.

PMID- 29022201
TI  - Increased mean platelet volume (MPV) is an independent predictor of inferior
      survival in patients with primary and secondary myelofibrosis.
AB  - Neoplastic megakaryopoiesis is a dominant feature of Philadelphia-chromosome
      negative myeloproliferative neoplasms (Ph- MPNs), and elevated mean-platelet
      volume (MPV) is a common finding in these diseases. The clinical and prognostic
      significances of MPV in patients with primary (PMF) and secondary myelofibrosis
      (SMF) have not been reported. We retrospectively analyzed 87 patients with
      myelofibrosis (66 with PMF, 21 with SMF) treated at our institution. MPV was
      recorded in addition to other hematological and clinical parameters. MPV was
      elevated in both PMF and SMF patients in comparison to controls, whereas there
      was no statistically significant difference between PMF and SMF. Elevated MPV was
      associated with lower platelets (P = 0.016), higher white blood cells (P =
      0.015), higher percentage of circulatory blasts (P = 0.009), higher lactate
      dehydrogenase (P = 0.011), larger spleen size (P = 0.014) and higher Dynamic
      International Prognostic score category (P = 0.027), while there was no
      statistically significant association with driver mutations or degree of bone
      marrow fibrosis. Higher MPV was univariately associated with inferior overall
      survival in the whole cohort (HR = 3.82, P = 0.006), PMF (HR = 4.35, P = 0.007)
      and SMF patients (HR = 7.22, P = 0.034). These associations remained significant
      in multivariate analyses adjusted for DIPSS. Higher MPV is associated with more
      aggressive disease features and exhibits powerful independent prognostic
      properties in both PMF and SMF settings.

PMID- 29022203
TI  - Modeling the Dynamics of Heterogeneity of Solid Tumors in Response to
      Chemotherapy.
AB  - In this paper, we extend the model of the dynamics of drug resistance in a solid
      tumor that was introduced by Lorz et al. (Bull Math Biol 77:1-22, 2015).
      Similarly to the original, radially symmetric model, the quantities we follow
      depend on a phenotype variable that corresponds to the level of drug resistance.
      The original model is modified in three ways: (i) We consider a more general
      growth term that takes into account the sensitivity of resistance level to high
      drug dosage. (ii) We add a diffusion term in space for the cancer cells and
      adjust all diffusion terms (for the nutrients and for the drugs) so that the
      permeability of the resource and drug is limited by the cell concentration. (iii)
      We add a mutation term with a mutation kernel that corresponds to mutations that
      occur regularly or rarely. We study the dynamics of the emerging resistance of
      the cancer cells under continuous infusion and on-off infusion of cytotoxic and
      cytostatic drugs. While the original Lorz model has an asymptotic profile in
      which the cancer cells are either fully resistant or fully sensitive, our model
      allows the emergence of partial resistance levels. We show that increased drug
      concentrations are correlated with delayed relapse. However, when the cancer
      relapses, more resistant traits are selected. We further show that an on-off drug
      infusion also selects for more resistant traits when compared with a continuous
      drug infusion of identical total drug concentrations. Under certain conditions,
      our model predicts the emergence of a heterogeneous tumor in which cancer cells
      of different resistance levels coexist in different areas in space.

PMID- 29022204
TI  - The relationship between single and two-dimensional indices of left ventricular
      size using hemodynamic transesophageal echocardiography in trauma and burn
      patients.
AB  - BACKGROUND: Conventional echocardiographic technique for assessment of volume
      status and cardiac contractility utilizes left ventricular end-diastolic area
      (LVEDA) and fractional area of change (FAC), respectively. Our goal was to find a
      technically reliable yet faster technique to evaluate volume status and
      contractility by measuring left ventricular end-diastolic diameter (LVEDD) and
      fractional shortening (FS) in a cohort of mechanically ventilated trauma and burn
      patients using hemodynamic transesophageal echocardiographic (hTEE) monitoring.
      METHODS: Retrospective chart review performed at trauma/burn intensive care unit
      (TBICU). Data on 88 mechanically ventilated surgical intensive care patients
      cared for between July 2013 and July 2015 were reviewed. Initial measurements of
      LVEDA, left ventricular end-systolic area (LVESA) and FAC were collected. Post
      processing left ventricular end-systolic (LVESD) and end-diastolic diameters
      (LVEDD) were measured and fractional shortening (FS) was calculated. Two
      orthogonal measurements of LV diameter were obtained in transverse (Tr) and
      posteroanterior (PA) orientation. RESULTS: There was a significant correlation
      between transverse and posteroanterior left ventricular diameter measurements in
      both systole and diastole. In systole, r = 0.92, p < 0.01 for LVESD-Tr (mean
      23.47 mm, SD +/- 6.77) and LVESD-PA (mean 24.84 mm, SD = 8.23). In diastole, r =
      0.80, p < 0.01 for LVEDD-Tr (mean 37.60 mm, SD +/- 6.45), and LVEDD-PA diameters
      (mean 42.24 mm, SD +/- 7.97). Left ventricular area (LVEDA) also significantly
      correlated with left ventricular diameter LVEDD-Tr (r = 0.84, p < 0.01) and LVEDD
      PA (r = 0.90, p < 0.01). Both transverse and PA measurements of fractional
      shortening were significantly (p < 0.0001) and similarly correlated with systolic
      function as measured by FAC. Bland-Altman analyses also indicated that the
      assessment of fractional shortening using left ventricular posteroanterior
      diameter measurement shows agreement with FAC. CONCLUSIONS: Left ventricular
      diameter measurements are a reliable and technically feasible alternative to left
      ventricular area measurements in the assessment of cardiac filling and systolic
      function.

PMID- 29022205
TI  - Development of FOCUS-GC: Framework for Outcomes of Clinical Communication
      Services in Genetic Counseling.
AB  - Conceptual frameworks bring together existing theories and models in order to
      identify, consolidate, and fill in gaps between theory, practice, and evidence.
      Given the vast number of possible outcomes that could be studied in genetic
      counseling, a framework for organizing outcomes and postulating relationships
      between communication services and genetic counseling outcomes was sought.
      Through an iterative approach involving literature review, thematic analysis, and
      consolidation, outcomes and processes were categorized to create and define
      components of a conceptual framework. The final product, "Framework for Outcomes
      of Clinical commUnication Services" (FOCUS) contains the following domains:
      communication strategy; communication process measures; patient care experience,
      patient changes, patient health; and family changes. A website was created to
      allow easier access and ongoing modifications to the framework. In addition, a
      step-by-step guide and two examples were created to show flexibility in how the
      framework can be used. FOCUS may help in conceptualizing, organizing and
      summarizing outcomes research related to risk communication and counseling in
      genetic service delivery as well as other healthcare settings.

PMID- 29022206
TI  - Effect of an alkaline environment on the engineering behavior of cement
      stabilized/solidified Zn-contaminated soils.
AB  - Although the stabilization/solidification method has been widely used for
      remediation of heavy metal-contaminated soils in recent decades, the engineering
      behavior and mobility of heavy metal ions under alkaline groundwater conditions
      are still unclear. Therefore, the unconfined compressive strength test (UCS)
      combined with toxicity characteristic leaching procedure (TCLP) and general acid
      neutralization capacity (GANC) was used to investigate the effects of alkalinity
      (using NaOH to simulate alkalinity in the environment) on the mechanical and
      leaching characteristics of cement-solidified/stabilized (S/S) Zn-contaminated
      soils. Moreover, the microstructure was analyzed using the scanning electron
      microscope (SEM) technology. The results indicated that alkaline environment
      could accelerate the UCS development compared with specimens without soaking in
      NaOH solution,, regardless of whether the specimens contained Zn2+ or not. And
      the UCS varied obviously attributed to the variations of both NaOH concentration
      and soaking time. Except for the specimens soaked for 90 days, the leached Zn2+
      concentrations were higher than that of without soaking. However, the
      leachability of Zn2+ in all the stabilized specimens is in the regulatory level.
      ANC results indicated that the Zn2+ leaching behavior can be divided into three
      stages related to the initial leachate pH. Moreover, SEM results proved that the
      alkaline environment could actually facilitate the cement hydration process. The
      results proved in the present paper could be useful in treating the heavy metal
      contaminated soils involved in the solidification/stabilization technology under
      alkaline environment.

PMID- 29022207
TI  - Mite diversity (Acari: Tetranychidae, Tydeidae, Iolinidae, Phytoseiidae) and
      within-tree distribution in citrus orchards in southern Spain, with special
      reference to Eutetranychus orientalis.
AB  - Mite diversity of selected citrus orchards in Andalusia (southern Spain) was
      studied during 2002-2007. The following species were found: Eutetranychus
      orientalis, Tetranychus urticae, Panonychus citri (Tetranychidae), Tydeus
      californicus, Lorryia formosa (Tydeidae), Pronematus ubiquitus (Iolinidae),
      Euseius stipulatus, Typhlodromus phialatus, Neoseiulus californicus, Euseius
      scutalis, Phytoseiulus persimilis, Paraseiulus talbii and Neoseiulus cucumeris
      (Phytoseiidae). Eutetranychus orientalis was the dominant tetranychid species in
      orange and lemon trees, whereas T. urticae was slightly more abundant in
      mandarines. The most abundant tydeid in clementine and orange was Tydeus
      californicus, in lemon it was L. formosa. The iolinid P. ubiquitus was found in
      very low numbers. With respect to phytoseiids, E. stipulatus was dominant in the
      three citrus species. Eutetranychus orientalis had a unimodal phenology, peaking
      only in autumn, whereas the other two tetranychids had two maxima. Tydeus
      californicus showed one or two peaks depending upon the citrus species, and E.
      stipulatus also had two peaks, one in spring and one in autumn. The mites
      displayed a non-random distribution in the tree. Eutetranychus orientalis
      preferred the outer and upper leaves. On the contrary, tydeids (mainly T.
      californicus) and phytoseiids (mainly E. stipulatus) preferred inner and lower
      leaves. These preferences had not been sufficiently described previously, and
      they are important for sampling plans.

PMID- 29022208
TI  - Hijacking cellular signals.

PMID- 29022209
TI  - Therapeutic doses of doxorubicin induce premature senescence of human mesenchymal
      stem cells derived from menstrual blood, bone marrow and adipose tissue.
AB  - Doxorubicin (Dox) is an effective anticancer drug with known activity against a
      wide spectrum of malignancies, hematologic malignancies in particular. Despite
      extensive clinical use, the mechanisms of its side effects and negative action on
      normal cells remain under study. The aim of this study was to investigate the
      effect of Dox on cultured human mesenchymal stem cells (MSCs) derived from
      menstrual blood (eMSCs), bone marrow (BMSCs) and adipose tissue (AMSCs). Dox
      treatment in high doses decreased the survival of MSCs in a dose-dependent
      manner. Clinically relevant low doses of Dox induced premature senescence of
      eMSCs, BMSCs and AMSCs, but did not kill the cells. Dox caused cell cycle arrest
      and formation of gamma-H2AX foci, and increased the number of SA-beta-gal
      positive cells. BMSCs entered premature senescence earlier than other MSCs. It
      has been reported that neural-like cells differentiated from MSCs of various
      origins are more sensitive to Dox than their parent cells. Dox-treated
      differentiated MSCs exhibited lower viability and earlier generation of gamma
      H2AX foci. Dox administration inhibited secretory activity in neural-like cells.
      These findings suggest that a clinically relevant Dox dose damages cultured MSCs,
      inducing their premature senescence. MSCs are more resistant to this damage than
      differentiated cells.

PMID- 29022210
TI  - Reducing catheter-related thrombosis using a risk reduction tool centered on
      catheter to vessel ratio.
AB  - In vascular access practices, the internal vessel size is considered important,
      and a catheter to vessel ratio (CVR) is recommended to assist clinicians in
      selecting the most appropriate-sized device for the vessel. In 2016, new practice
      recommendations stated that the CVR can increase from 33 to 45% of the vessels
      diameter. There has been evidence on larger diameter catheters and increased
      thrombosis risk in recent literature, while insufficient information established
      on what relationship to vessel size is appropriate for any intra-vascular device.
      Earlier references to clinical standards and guidelines did not clearly address
      vessel size in relation to the area consumed or external catheter diameter. The
      aim of this manuscript is to present catheter-related thrombosis evidence and
      develop a standardized process of ultrasound-guided vessel assessment,
      integrating CVR, Virchow's triad phenomenon and vessel health and preservation
      strategies, empowering an evidence-based approach to device placement. Through
      review, calculation and assessment on the areas of the 33 and 45% rule, a
      preliminary clinical tool was developed to assist clinicians make cognizant
      decisions when placing intravascular devices relating to target vessel size,
      focusing on potential reduction in catheter-related thrombosis. Increasing the
      understanding and utilization of CVRs will lead to a safer, more consistent
      approach to device placement, with potential thrombosis reduction strategies. The
      future of evidence-based data relies on the clinician to capture accurate vessel
      measurements and device-related outcomes. This will lead to a more dependable
      data pool, driving the relationship of catheter-related thrombosis and vascular
      assessment.

PMID- 29022211
TI  - Subjective Global Nutritional Assessment: A Reliable Screening Tool for
      Nutritional Assessment in Cerebral Palsy Children.
AB  - OBJECTIVE: To determine the prevalence of undernutrition in children with
      cerebral palsy and to compare subjective and objective methods of nutritional
      assessment. METHODS: This was a hospital based analytical observational study in
      which 180 children of cerebral palsy, aged 1-12 y, attending tertiary level
      hospital, Jaipur from March, 2012 through March, 2013 were included. Subjective
      assessment was done by questionnaire (Subjective Global Nutritional Assessment;
      SGNA) in which questions related to nutrition history and physical examination,
      signs of fat, muscle wasting and edema was done while objective assessment was
      done by weight, height and triceps skinfold thickness (TSFT) measurements.
      RESULTS: In this study prevalence of undernutrition by subjective method (SGNA)
      was 76.67% while by objective measurement (weight, height, TSFT) was 48.89%,
      77.78% 35.18% respectively. There was fair to moderate agreement between the SGNA
      and objective assessments including weight and height (k = 0.341, p = 0.000; k =
      0.337, p = 0.000 respectively) while for TSFT agreement between both methods was
      poor (k = 0.092, p = 0.190). In the index study, sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV) of SGNA was
      for weight was 95%, 37%, 56%, 90%; for height 84%, 50%, 85%, 47%; for TSFT 81%,
      30%, 38%, 75% respectively. CONCLUSIONS: The prevalence of undernutrition is high
      in cerebral palsy children. SGNA can be a reliable tool for assessing nutritional
      status in children with cerebral palsy and is a simple, comprehensive,
      noninvasive, and cost-effective tool for screening undernutrition in children of
      cerebral palsy.

PMID- 29022212
TI  - Effect of Food on the Pharmacokinetics of Saroglitazar Magnesium, a Novel Dual
      PPARalphagamma Agonist, in Healthy Adult Subjects.
AB  - BACKGROUND AND OBJECTIVE: Peroxisome proliferator-activated receptors (PPARs)
      have recently become a focus of interest for their important roles in glucose and
      lipid metabolism. In humans, PPARalpha activation causes a decrease in plasma
      triglyceride (TG) levels, enhancement of high-density lipoprotein cholesterol
      (HDL-C) and simultaneous enhancement of very-low-density lipoprotein (VLDL)
      lipolysis, whereas PPARgamma agonists act as insulin sensitizers and improve
      insulin resistance, which is very useful in patients with type 2 diabetes
      mellitus (T2DM). Saroglitazar magnesium is a dual PPAR agonist with potent
      predominant PPARalpha and moderate PPARgamma activity and the first glitazar to
      be granted marketing authorization in India. This study was conducted to evaluate
      the oral bioavailability and safety and tolerability of a LipaglynTM
      (saroglitazar magnesium) 4-mg tablet in healthy, adult human subjects under fed
      relative to fasting conditions. METHODS: This was a single-dose, open-label,
      randomized, single-treatment, two-period, two-conditions (fed vs. fasting), two
      sequence, crossover study planned in 54 healthy subjects. Food effect (high
      calorie and high-fat breakfast) was examined by comparing pharmacokinetic data of
      saroglitazar and its metabolite saroglitazar sulfoxide in plasma samples
      collected pre-dose and serially up to 72 h post-dose. Pharmacokinetic data were
      analyzed using the standard non-compartmental approach. RESULTS: A total of 54
      subjects were enrolled in the study, out of them 50 subjects had completed the
      study and were analyzed. The presence of food had a minor impact on the
      disposition of saroglitazar. While food reduced C max (maximum concentration) of
      saroglitazar by 30%, the extent of absorption as measured by AUCinfinity (area
      under the concentration time curve from time zero to infinity) was not
      influenced. This was further supported by the bioequivalence data between fasted
      and fed conditions for saroglitazar, where 90% CIs (confidence intervals) of the
      adjusted geometric mean of the fed relative to the fasted condition ranged from
      101.37% to 108.07% for AUCinfinity and from 63.45% to 74.68% for C max. Other
      parameters such as T max (time of maximum concentration) and T 1/2 (elimination
      half-life) were not influenced by the food intake. Saroglitazar was well
      tolerated in the study, and the reported adverse events were mild in nature.
      CONCLUSION: For the single-dose study, the absorption rate is affected by food as
      the 90% CI of C max is outside 80.00-125.00%. However, there is no impact of food
      on the extent of absorption of saroglitazar. The observed lower C max of
      saroglitazar with food has no clinical relevance since the therapeutic efficacy
      of saroglitazar was achieved after multiple-dose administration, suggesting the
      importance of total exposure.

PMID- 29022213
TI  - High prevalence of heparin induced thrombocytopenia with thrombosis among
      patients with essential thrombocytemia carrying V617F mutation.
AB  - Arterial and venous complications are major causes of morbidity and mortality in
      myeloproliferative neoplasms (MPNs). MPNs patients, frequently receive heparin.
      Heparin-induced thrombocytopenia (HIT) is a rare but potentially life-threatening
      complication resulting in a severe acquired thrombophilic condition. We carried
      out a retrospective analysis to evaluate occurrence of new thrombotic events
      during heparin therapy in essential thrombocythemia (ET) patients. We studied 108
      ET patients on heparin for treatment of previous thrombotic events or in
      thromboprophilaxis. Fifty-eight of them carried JAK 2 V617F mutation while 50
      patients were without V617F mutation. Ten patients, among those with JAK 2 V617F
      mutation after a median of 10 days from heparin treatment presented a platelet
      drop, new thrombotic events and in 10/10 cases heparin-related antibodies were
      found. In the other group, two patients (4%) presented a platelet drop,
      thrombotic manifestations and heparin related antibodies. Our data show that HIT
      is more frequent, during heparin treatment, in patients with ET carrying V617F
      mutation, as compared with patients without mutations (P = 0.029). ET with V617F
      mutation seems to be associated with higher risk of thrombotic complications
      during heparin treatment. Monitoring platelet counts very closely during the
      course of heparin is essential especially in ET patients in which platelet drop
      may be hidden by constitutional thrombocytosis.

PMID- 29022214
TI  - Two new species of Trouessartia Canestrini, 1899 (Astigmata: Trouessartiidae)
      from passeriform birds in Brazil.
AB  - Two new feather mite species of the genus Trouessartia Canestrini, 1899
      (Analgoidea: Trouessartiidae) are described from passerines (Aves: Passeriformes)
      in Brazil: T. calcealgiana n. sp. from Philydor atricapillus (Wied)
      (Furnariidae), and T. gigaphallus n. sp. from Tyrannus melancholicus Vieillot
      (Tyrannidae). Both species have unique features, such as the large hook-like seta
      sR on trochanters III in T. calcealgiana, and the large male genitalia in T.
      gigaphallus, which are at least twice as long as normally found in most species
      of Trouessartia.

PMID- 29022215
TI  - Effectiveness of a new dental implant bioactive surface: histological and
      histomorphometric comparative study in minipigs.
AB  - OBJECTIVES: The objective of this study was to assess, by histomorphometric
      analysis, the degree of bone apposition on two types of dental implant's
      surfaces: a novel implant that combines Al2O3 abrasive particle blasting with
      thermochemical treatment (ContacTi), compared to a standard surface treatment
      obtained by sandblasting and acid etching (shot blasting). MATERIALS AND METHODS:
      Twelve minipigs were used, placing the studied implants in the maxillae, and
      divided into three groups according to the time of sacrifice: 2, 4, and 8 weeks
      after implant placement. Histological and histomorphometric analyses were
      performed following standardized tissue polymerization, cutting, and staining and
      examined under optical and high-resolution electron microscope. RESULTS: For all
      measurements, the novel surface presented higher levels of osseointegration as
      compared to the shot blasting surface. Bone to implant contact (BIC) in the
      maxillae for ContacTi presented values of 49.02, 83.20, and 85.58% at 2, 4, and 8
      weeks, respectively, significantly higher compared to the shot blasting surface
      values of 39.32, 46.53, and 46.20% for the same time points. Bone area density
      (BAD) presented values of 26.52, 61.21, and 59.50% for ContacTi surface implants
      and 22.95, 36.26, and 49.50% for the shot blasted surface implants. Signs of
      osteoconductivity were observed in the ContacTi surfaces at 2 weeks. CONCLUSIONS:
      The ContacTi surface achieved a faster growth of hard tissues around the
      implants, when compared to the shot blasting surface, and for all evaluated
      histomorphometric parameters, the values were higher at all measured time points.
      CLINICAL RELEVANCE: ContacTi could be a new surface improving the
      osseointegration in oral implantology.

PMID- 29022216
TI  - Initial evaluation of the Celesteion large-bore PET/CT scanner in accordance with
      the NEMA NU2-2012 standard and the Japanese guideline for oncology FDG PET/CT
      data acquisition protocol version 2.0.
AB  - BACKGROUND: The goal of this study was to evaluate the performance of the
      Celesteion positron emission tomography/computed tomography (PET/CT) scanner,
      which is characterized by a large-bore and time-of-flight (TOF) function, in
      accordance with the NEMA NU-2 2012 standard and version 2.0 of the Japanese
      guideline for oncology fluorodeoxyglucose PET/CT data acquisition protocol.
      Spatial resolution, sensitivity, count rate characteristic, scatter fraction,
      energy resolution, TOF timing resolution, and image quality were evaluated
      according to the NEMA NU-2 2012 standard. Phantom experiments were performed
      using 18F-solution and an IEC body phantom of the type described in the NEMA NU-2
      2012 standard. The minimum scanning time required for the detection of a 10-mm
      hot sphere with a 4:1 target-to-background ratio, the phantom noise equivalent
      count (NECphantom), % background variability (N 10mm), % contrast (Q H,10mm), and
      recovery coefficient (RC) were calculated according to the Japanese guideline.
      RESULTS: The measured spatial resolution ranged from 4.5- to 5-mm full width at
      half maximum (FWHM). The sensitivity and scatter fraction were 3.8 cps/kBq and
      37.3%, respectively. The peak noise-equivalent count rate was 70 kcps in the
      presence of 29.6 kBq mL-1 in the phantom. The system energy resolution was 12.4%
      and the TOF timing resolution was 411 ps at FWHM. Minimum scanning times of 2, 7,
      6, and 2 min per bed position, respectively, are recommended for visual score,
      noise-equivalent count (NEC)phantom, N 10mm, and the Q H,10mm to N 10mm ratio
      (QNR) by the Japanese guideline. The RC of a 10-mm-diameter sphere was 0.49,
      which exceeded the minimum recommended value. CONCLUSIONS: The Celesteion large
      bore PET/CT system had low sensitivity and NEC, but good spatial and time
      resolution when compared to other PET/CT scanners. The QNR met the recommended
      values of the Japanese guideline even at 2 min. The Celesteion is therefore
      thought to provide acceptable image quality with 2 min/bed position acquisition,
      which is the most common scan protocol in Japan.

PMID- 29022217
TI  - Sepsis: A Review of Advances in Management.
AB  - Infections represent a common health problem in people of all ages. Usually, the
      response given to them is appropriate and so little treatment is needed.
      Sometimes, however, the response to the infection is inadequate and may lead to
      organ dysfunction; this is the condition known as sepsis. Sepsis can be caused by
      bacteria, fungi or viruses and at present there is no specific treatment; its
      management basically focuses on containing the infection through source control
      and antibiotics plus organ function support. This article reviews key elements of
      sepsis management, focusing on diagnosis, biomarkers and therapy. The main recent
      advance in therapy is the strategy of personalized medicine, based on a precise
      approach using biomarkers to identify specific individuals who are likely to
      benefit from more personalized attention.

PMID- 29022219
TI  - Photoreduction of Cr(VI) in water using BiVO4-Fe3O4 nano-photocatalyst under
      visible light irradiation.
AB  - The residuals of hexavalent chromium in the aquatic environment have raised much
      concern for water decontamination. In this study, BiVO4-Fe3O4 was synthesized
      using a solvothermal method and adopted as a photoreduction catalyst to removal
      of Cr(VI) in water under visible light irradiation. The physical and chemical
      properties of BiVO4-Fe3O4 were characterized by UV-vis-DRS, SEM, XRD, FTIR, and
      BET. The results demonstrated that the band gap for the obtained material is 1.74
      eV with an average size of 15 nm and a specific surface area of 55.16 m2/g. A
      high photocatalytic performance was observed on the photoreduction of Cr(VI) and
      the removal efficiency was increased in the lower pH condition. The ascending
      catalyst dosages made the promotion effect, while the increase of Cr(VI)
      concentration contributed the inhibition for the reduction performance. The
      structural characteristics of the selected hole scavengers (ethanol, isopropanol,
      formic acid, citric acid, and oxalic acid) showed the various effects on the
      reactions due to the amounts of alpha-OH. For the optimal condition, 79.37%
      Cr(VI) was removed. Based on the excellent reusability of BiVO4-Fe3O4, this study
      demonstrated a potential method for the economic-friendly removal of high-valence
      metals with easier separation in the water.

PMID- 29022221
TI  - Eating disorder symptoms and the 2 * 2 model of perfectionism: mixed
      perfectionism is the most maladaptive combination.
AB  - PURPOSE: The 2 * 2 model of perfectionism (Gaudreau and Thompson in Personal
      Individ Diff 48:532-537, 2010) represents an important addition to the
      perfectionism literature, but so far has not been studied in relation with
      disordered eating. METHOD: Using the 2 * 2 model as analytic framework, this
      study examined responses from a convenience sample of 716 participants aged 19-68
      years (71% female) investigating how self-oriented perfectionism (SOP) and
      socially prescribed perfectionism (SPP) predicted individual differences in
      eating disorder symptoms, additionally controlling for body mass index, gender,
      and age. RESULTS: Results showed a significant SOP * SPP interaction indicating
      that the combination of high SOP and high SPP-called "mixed perfectionism"-was
      associated with the highest levels of eating disorder symptoms. CONCLUSIONS: The
      findings demonstrate the utility of the 2 * 2 model of perfectionism as an
      analytic framework for examining perfectionism and disordered eating. Moreover,
      they suggest that mixed perfectionism is the most maladaptive form of
      perfectionism when it comes to disordered eating, such that having high levels of
      SPP combined with high levels of SOP represents the most maladaptive combination
      of perfectionism in terms of risk of eating disorder. LEVEL OF EVIDENCE: Level V,
      cross-sectional descriptive study.

PMID- 29022218
TI  - An examination of the mechanisms and personality traits underlying food addiction
      among individuals with severe obesity awaiting bariatric surgery.
AB  - PURPOSE: The aetiology underlying addiction has often been investigated to shed
      more light on the factors contributing to the development and maintenance of
      various disorders. In the field of addictive eating behaviours, data on the
      aetiological factors related to food addiction (FA) in the bariatric context
      remain scarce. The present study aimed to explore mechanisms and variables
      underlying FA among individuals suffering from severe obesity and awaiting
      bariatric surgery. METHODS: Participants (N = 146) were recruited at the Quebec
      Heart and Lung Institute during their pre-operative visit and were invited to
      complete questionnaires. Participants with and without FA were compared on reward
      sensitivity, impulsivity, emotion dysregulation, and personality traits. RESULTS:
      Findings showed that bariatric candidates with FA (16%) presented more emotion
      dysregulation, more harm avoidance, and less self-directedness. Further
      exploration showed that the association between harm avoidance and the number of
      FA criteria endorsed was mediated by emotion dysregulation, while the association
      between self-directedness and the number of FA criteria endorsed was mediated by
      reward sensitivity. CONCLUSIONS: These results indicate that an inability to
      regulate affect by strategies other than eating highly palatable food, in a
      context where negative affect and long-term goals can hardly be sustained,
      underlies a diagnostic of FA among bariatric candidates. From a clinical
      standpoint, the presence of a double vulnerability leading to FA symptomatology
      could help design better-targeted interventions to maximise weight loss
      maintenance in the bariatric context. LEVEL OF EVIDENCE: Level V, descriptive
      study.

PMID- 29022220
TI  - An overview of concepts and approaches used in estimating the burden of
      congenital disorders globally.
AB  - Congenital disorders are an important cause of pregnancy loss, premature death
      and life-long disability. A range of interventions can greatly reduce their
      burden, but the absence of local epidemiological data on their prevalence and the
      impact of interventions impede policy and service development in many countries.
      In an attempt to overcome these deficiencies, we have developed a tool-The Modell
      Global Database of Congenital Disorders (MGDb) that combines general biological
      principles and available observational data with demographic data, to generate
      estimates of the birth prevalence and effects of interventions on mortality and
      disability due to congenital disorders. MGDb aims to support policy development
      by generating country, regional and global epidemiological estimates. Here we
      provide an overview of the concepts and methodological approach used to develop
      MGDb.

PMID- 29022223
TI  - Acute kidney injury in pregnancy and the role of underlying CKD: a point of view
      from Mexico.
AB  - The incidence of acute kidney injury in pregnancy (P-AKI) in developed countries
      is significantly lower than in developing ones, where it is estimated to range
      between 4 and 26%. Mortality in cases of P-AKI requiring dialysis is high,
      varying from 20 to 80%. In developing countries, clinical decisions are often
      based on the availability of services and not on needs. Prenatal surveillance in
      Mexico does not include serum creatinine, limiting the potential for early
      diagnosis of AKI and CKD and their differential diagnosis. There are few
      specialized centers for the care of a pregnancy complicated with kidney disease
      in Mexico. P-AKI superimposed on preexistent, and usually undiagnosed CKD, is
      common: in Guadalajara 10 out of the 27 patients with Stage 3-5 CKD or nephrotic
      proteinuria, that were followed in 2013-2015, required renal replacement therapy
      (RRT) in pregnancy; in the same period in Mexico City out of 18 patients with P
      AKI requiring dialysis, 5 remained dialysis dependent, 3 started dialysis in the
      following year after their pregnancy and only 1 fully recovered renal function.
      The grim prognosis is exacerbated by the fact that 70% of Mexicans are not
      reimbursed for dialysis, and pregnancy-related coverage lasts for only 42 days
      after delivery. Perinatal results are no less troubling, as most patients with P
      AKI give birth preterm to small or very small babies. While our data do not allow
      us to evaluate needs, they do make it possible to define the complexity of the
      problems faced in the care of P-AKI in Mexico. Early diagnosis of P-AKI and
      chronic kidney disease (CKD) is needed to protect mothers and children and the
      country urgently needs programs to enable it to fulfil the World Health
      Organization's imperative that we "make every mother and child count".

PMID- 29022224
TI  - Prepulse Inhibition of Auditory Cortical Responses in the Caudolateral Superior
      Temporal Gyrus in Macaca mulatta.
AB  - Prepulse inhibition (PPI) refers to a decreased response to a startling stimulus
      when another weaker stimulus precedes it. Most PPI studies have focused on the
      physiological startle reflex and fewer have reported the PPI of cortical
      responses. We recorded local field potentials (LFPs) in four monkeys and
      investigated whether the PPI of auditory cortical responses (alpha, beta, and
      gamma oscillations and evoked potentials) can be demonstrated in the caudolateral
      belt of the superior temporal gyrus (STGcb). We also investigated whether the
      presence of a conspecific, which draws attention away from the auditory stimuli,
      affects the PPI of auditory cortical responses. The PPI paradigm consisted of
      Pulse-only and Prepulse + Pulse trials that were presented randomly while the
      monkey was alone (ALONE) and while another monkey was present in the same room
      (ACCOMP). The LFPs to the Pulse were significantly suppressed by the Prepulse
      thus, demonstrating PPI of cortical responses in the STGcb. The PPI-related
      inhibition of the N1 amplitude of the evoked responses and cortical oscillations
      to the Pulse were not affected by the presence of a conspecific. In contrast,
      gamma oscillations and the amplitude of the N1 response to Pulse-only were
      suppressed in the ACCOMP condition compared to the ALONE condition. These
      findings demonstrate PPI in the monkey STGcb and suggest that the PPI of auditory
      cortical responses in the monkey STGcb is a pre-attentive inhibitory process that
      is independent of attentional modulation.

PMID- 29022226
TI  - Parents' and Physicians' Perceptions of Children's Participation in Decision
      making in Paediatric Oncology: A Quantitative Study.
AB  - The goal is to present how shared decision-making in paediatric oncology occurs
      from the viewpoints of parents and physicians. Eight Swiss Pediatric Oncology
      Group centres participated in this prospective study. The sample comprised a
      parent and physician of the minor patient (<18 years). Surveys were statistically
      analysed by comparing physicians' and parents' perspectives and by evaluating
      factors associated with children's actual involvement. Perspectives of ninety-one
      parents and twenty physicians were obtained for 151 children. Results indicate
      that for six aspects of information provision examined, parents' and physicians'
      perceptions differed. Moreover, parents felt that the children were more
      competent to understand diagnosis and prognosis, assessed the disease of the
      children as worse, and reported higher satisfaction with decision-making on the
      part of the children. A patient's age and gender predicted involvement. Older
      children and girls were more likely to be involved. In the decision-making
      process, parents held a less active role than they actually wanted. Physicians
      should take measures to ensure that provided information is understood correctly.
      Furthermore, they should work towards creating awareness for systematic
      differences between parents and physicians with respect to the perception of the
      child, the disease, and shared decision-making.

PMID- 29022229
TI  - Luciano Martini (1927-2017): a memoir.

PMID- 29022227
TI  - Giving Back to Families: Evidence and Predictors of Persons with Serious Mental
      Illness Contributing Help and Support to Families.
AB  - Persons with serious mental illness (SMI) often rely on family for significant
      assistance and support, but the contributions made by persons with SMI to their
      families have been overlooked. This study assessed the extent to which persons
      with SMI contribute help or support to their families and identified significant
      predictors of contribution using an analysis of 1 year of clinicians' electronic
      health record (EHR) notes. EHR notes with reference to families of 226 Veterans
      with SMI were extracted and classified as suggesting help being given to and/or
      received from families. Forty-one percent of the sample contributed to family in
      a variety of ways. More frequent contact with family and being female were
      significant predictors of contribution. This study underlines the potential for
      reciprocal relationships within families of individuals with SMI. Clinicians can
      help clients and families maximize the support they provide to one another and
      possibly improve outcomes.

PMID- 29022228
TI  - The development and treatment of a food phobia after bariatric surgery.

PMID- 29022230
TI  - Prof. Gian Franco Bottazzo MD FRCP FRCPath (1946-2017).

PMID- 29022222
TI  - T Cell Receptor Profiling in Type 1 Diabetes.
AB  - PURPOSE OF REVIEW: The genetic susceptibility and dominant protection for type 1
      diabetes (T1D) associated with human leukocyte antigen (HLA) haplotypes, along
      with minor risk variants, have long been thought to shape the T cell receptor
      (TCR) repertoire and eventual phenotype of autoreactive T cells that mediate beta
      cell destruction. While autoantibodies provide robust markers of disease
      progression, early studies tracking autoreactive T cells largely failed to
      achieve clinical utility. RECENT FINDINGS: Advances in acquisition of pancreata
      and islets from T1D organ donors have facilitated studies of T cells isolated
      from the target tissues. Immunosequencing of TCR alpha/beta-chain complementarity
      determining regions, along with transcriptional profiling, offers the potential
      to transform biomarker discovery. Herein, we review recent studies characterizing
      the autoreactive TCR signature in T1D, emerging technologies, and the challenges
      and opportunities associated with tracking TCR molecular profiles during the
      natural history of T1D.

PMID- 29022231
TI  - Calcium Channel Blockers for the Clinical Management of Hypertension.

PMID- 29022232
TI  - A case of fatal perimyocarditis due to a rare disease.
AB  - Although myocarditis is caused by viral infections in about 50% of cases in
      European countries, various other causative agents are known. We report the case
      of a 51-year-old man who died several months after being diagnosed with asthma by
      his general practitioner. This diagnosis had been confirmed by a pulmonologist
      approximately 6 weeks before the man's death. To rule out the possibility of
      medical malpractice the prosecuting authority ordered a forensic autopsy. At
      autopsy macroscopic indicators for perimyocarditis and pneumonia were found.
      Microbiological and histological examination of tissue samples confirmed a
      diagnosis of Churg-Strauss syndrome, also known as Eosinophilic Granulomatosis
      with Polyangiitis (EGPA). The cause of death was determined to be cardiac
      involvement in Churg-Strauss syndrome. The presence of this disease also
      accounted for the man's recent medical history. There were no findings to
      indicate that a medical error had been made. The reported case illustrates why
      accessory histological and microbiological examinations should always be
      performed when macroscopic findings at autopsy suggest myocarditis. Determining
      the etiology of myocarditis is a necessary step to prevent overlooking rare
      diseases with inflammatory myocardial involvement, especially in the
      clarification of alleged medical malpractice.

PMID- 29022233
TI  - Unanticipated Cardiotoxicity Associated with Targeted Anticancer Therapy in
      Patients with Hematologic Malignancies Patients: Natural History and Risk
      Factors.
AB  - Our aim is to study unanticipated cardiotoxicity associated with the use of
      anticancer targeted agents, a problem that remains poorly understood. Using
      diagnosis codes, we retrospectively identified patients with both hematologic
      malignancies (HM) and cardiovascular diseases (n = 820 patients). Cardiotoxicity
      was defined per published criteria. The targeted agents of interest included
      tyrosine kinase inhibitors, proteasome inhibitors, monoclonal antibodies, and
      immunomodulatory agents. Patients found with cardiotoxicity (n = 29) were
      compared with 70 case-matched reference subjects. Median time from targeted
      therapy exposure to cardiotoxicity was 132 days. A higher percentage of patients
      had prior exposure to anthracyclines in study versus reference group (65.5 vs.
      42.8%, P = 0.04), however, did not stay significant in multivariate analysis. Two
      variables were significant predictors, prior of DVT/PE and Karnofsky score of >=
      80% (P <= 0.011). Only 2 study group patients died of cardiac causes. Most
      cardiotoxicity patients (23/29) had remained stable or improved, while 21
      patients received further chemotherapy. OS was lower in the study group (P =
      0.018) versus the reference group. In conclusion, a small number patients with HM
      experience unanticipated cardiotoxicity with low related mortality. Risk of
      cardiotoxicity was significantly associated with history of DVT/PE. Most patients
      do well, but despite that, their OS is significantly poorer.

PMID- 29022234
TI  - Selflessness as a predictor of remission from an eating disorder: 1-4 year
      outcomes from an adolescent day-care unit.
AB  - OBJECTIVE: To assess the potential role of selflessness in predicting remission
      from an eating disorder (ED) following discharge from an adolescent day-care
      unit. METHOD: Participants were 95 female patients (aged 13-19 years) with an ED
      diagnosis across the spectrum admitted to an adolescent day-care unit for EDs
      between 2008 and 2012. Forty-one of these participants completed the follow-up
      assessment, between 12 and 46 months following discharge. No significant
      differences were found in Time 1 variables between patients who participated in
      Time 2 and those who did not. At both time points, ED and psychiatric comorbidity
      diagnoses were made using standard structured interviews. Patients were also
      administered the Beck Depression Inventory (BDI), the State-Trait Anxiety
      Inventory (STAI), The Eating Attitude Test (EAT-26), The Eating Disorder
      Inventory (EDI-2) and the Selflessness Scale (SS)*. RESULTS: Only baseline
      Selflessness Scale was significant in predicting the continuous variable of ED
      symptomatology level in follow-up. When dividing EDI total score into its
      subscales at baseline, one of those, maturity fears, was found, together with the
      SS, significant in the prediction. In predicting remission (this time as a
      dichotomized variable) in follow-up, only the SS, maturity fears, EDI total, and
      EAT-26, at baseline, predicted remission at follow-up, but the strength of
      selflessness was the greatest. CONCLUSIONS: Psychological features are not the
      main target of the important search for predictors of remission from ED. The
      findings of the present study add the psychological feature of selflessness to
      this search. Psychotherapy can be enriched by identifying psychological features
      such as selflessness as one of its foci. The present findings might also renew
      interest in maturity fears as an additional focus in psychotherapy. LEVEL OF
      EVIDENCE: Level III, cohort study.

PMID- 29022235
TI  - Correction to: Meta-barcoding in combination with palynological inference is a
      potent diagnostic marker for honey floral composition.
AB  - In the version of this article that was originally published (Laha et al. 2017)
      the authors did not properly reference one paragraph in the Introduction section.

PMID- 29022236
TI  - The Protective Effect of Selenium on Bovine Mammary Epithelial Cell Injury Caused
      by Depression of Thioredoxin Reductase.
AB  - To elucidate the effect of selenium (Se) on antioxidant function of mammary
      glands in dairy cows and the underlying mechanism, an experiment was conducted
      using a single-factor completely randomized design study. Bovine mammary
      epithelial cells (BMECs) were randomly divided into four groups: control, Se
      treatment, 2,4-dinitrochlorobenzene (DNCB) inhibition, and Se prevention.
      Treatment of BMECs with Se was found to significantly reverse decreased cell
      proliferation and the expression of thioredoxin reductase (TrxR) after DNCB
      exposure. DNCB-induced activation of apoptosis signaling kinase-1 (ASK-1), which
      activates the mitogen-activated protein kinase (MAPK) pathway, was reduced in
      BMECs treated with Se. Additionally, our results indicated that Se treatment
      resulted in lower intracellular accumulation of arachidonic acid (ARA) and 15
      hydroperoxyeicosatetraenoic acid (15-HPETE) due to suppressed expression of
      cytosolic phospholipase A2 (cPLA2) regulated by p38MAPK and c-Jun N-terminal
      kinase (JNK) in DNCB-stimulated BMECs. Taken together, these findings suggest
      that Se treatment improved the antioxidant function of dairy cow mammary glands
      and protected cells from oxidative damage primarily by increasing the activity of
      TrxR, inhibiting the activation of the MAPK signaling pathway, and thus
      decreasing the content of ARA and its related metabolites.

PMID- 29022238
TI  - Predicting the Happiness of Adolescents Based on Coping Styles and Religious
      Attitudes.
AB  - The study aimed to predict the happiness of adolescents based on coping styles
      and religious attitudes. To this end, the correlational research methodology was
      used. In total, 381 subjects were selected from adolescents of Semnan (Eastern
      province of Iran), using multistage clustering sampling method. Research tools
      were Ways of Coping Questionnaire by Lazarus, Golriz and Barahani's Religious
      Attitude Questionnaire, and Oxford Happiness Questionnaire. Data analysis was
      performed in SPSS using Pearson's correlation coefficient and multiple regression
      analysis. Results of Pearson's correlation demonstrated a significant positive
      relationship between happiness of adolescents and variables of problem-focused
      coping styles (r = 0.31, P < 0.01) and religious attitudes (r = 0.129, P < 0.05).
      Meanwhile, a negative significant association was observed between emotion
      focused coping styles and happiness (r = -0.184, P < 0.01). Moreover, results of
      multiple regression analysis indicated that the listed variables explained 17% of
      the variance of happiness in totality. According to the results, it is
      recommended that use of problem-focused styles be emphasized in addition to
      strengthening of religious attitudes to increase the happiness of adolescents.

PMID- 29022237
TI  - Dysfunction of Membrane Trafficking Leads to Ischemia-Reperfusion Injury After
      Transient Cerebral Ischemia.
AB  - Neurons require an extraordinarily high level of membrane trafficking activities
      because of enriched axonal terminals and dendritic branches. For that reason,
      defects in the membrane trafficking pathway are a hallmark of most, and may be
      all, neurodegenerative disorders. A major cellular membrane trafficking pathway
      is the Golgi apparatus (Golgi hereafter)-late endosome-lysosome axis for
      supplying lysosomal enzymes. This pathway is regulated by N-ethylmaleimide
      sensitive factor (NSF) ATPase. This review article is to discuss a novel
      hypothesis that brain ischemia inactivates NSF ATPase, resulting in a cascade of
      events of disruption of the Golgi-endosome-lysosome pathway, release of cathepsin
      B (CTSB), and induction of mitochondrial outer membrane permeabilization (MOMP)
      during the postischemic phase. This hypothesis is supported by recent studies
      demonstrating that NSF is trapped into inactive protein aggregates in neurons
      destined to die after brain ischemia. Consequently, Golgi, transport vesicles
      (TVs), and late endosomes (LEs) are accumulated and damaged, which is followed by
      CTSB release from these damaged structures. Moderate release of CTSB cleaves Bax
      like BH3 protein (Bid) to become active truncated Bid (tBid). Active tBid is then
      translocated to the mitochondrial outer membrane, resulting in oligomerization of
      BCL2-associated X protein (Bax) forming the mitochondrial outer membrane pores,
      and releasing mitochondrial intramembranous proteins. Extensive CTSB release,
      however, can digest cellular proteins indiscriminately to induce cell death.
      Based on these new observations, we propose a novel hypothesis, i.e., brain
      ischemia leads to NSF inactivation, resulting in a massive buildup of damaged
      Golgi, TVs and LEs, fatal release of CTSB, induction of MOMP, and eventually
      brain ischemia-reperfusion injury.

PMID- 29022239
TI  - Application of EGFR inhibitor reduces circulating tumor cells during
      transcatheter arterial embolization.
AB  - PURPOSE: Transcatheter arterial embolization (TAE) has been widely used in
      treating non-curative hepatocellular carcinoma (HCC). However, it is noticed that
      TAE may cause invasion of some cancer cells into circulation, resulting in distal
      metastasis and poor therapeutic outcome. Here, we aimed to reduce the side
      effects of TAE using the inhibitors for epidermal growth factor receptor (EGFR).
      METHODS: Transient hepatic artery ligation (HAL) was used as a mouse model for
      TAE. EGFR inhibitors were applied. Tumor size, presence of tumor cells in
      circulation, distal tumor formation, and activation of genes associated with
      tumor cell invasion and metastasis were analyzed. RESULTS: Inhibitors for EGFR
      significantly reduced the size of primary tumor, presence of tumor cells in
      circulation, and distal tumor formation after HAL. Further studies showed that
      EGFR inhibition suppressed several genes associated with tumor cell invasion and
      metastasis, such as vascular endothelial growth factor-A, stromal cell-derived
      factor 1, and Slug. CONCLUSION: EGFR inhibitor application may reduce circulating
      cancer cells during TAE and thus improve the therapy for advanced HCC.

PMID- 29022240
TI  - Mercury alters initiation and construction of nests by zebra finches, but not
      incubation or provisioning behaviors.
AB  - Mercury is an environmental contaminant that impairs avian reproduction, but the
      behavioral and physiological mechanisms underlying this effect are poorly
      understood. The objective of this study was to determine whether lifetime dietary
      exposure to mercury (1.2 ug/g wet weight in food) impacted avian parental
      behaviors, and how this might influence reproductive success. To distinguish
      between the direct effects of mercury on parents and offspring, we created four
      treatment groups of captive-bred zebra finches (Taeniopygia guttata), with
      control and mercury-exposed adults raising cross-fostered control or mercury
      exposed eggs (from maternal transfer). Control parents were 23% more likely to
      fledge young than parents exposed to mercury, regardless of egg exposure. Mercury
      exposed parents were less likely to initiate nests than controls and spent less
      time constructing them. Nests of mercury-exposed pairs were lighter, possibly due
      to an impaired ability to bring nest material into the nestbox. However, nest
      temperature, incubation behavior, and provisioning rate did not differ between
      parental treatments. Unexposed control eggs tended to have shorter incubation
      periods and higher hatching success than mercury-exposed eggs, but there was no
      effect of parental exposure on these parameters. We accidentally discovered that
      parent finches transfer some of their body burden of mercury to nestlings during
      feeding through secretion in the crop. These results suggest that, in mercury
      exposed songbirds, pre-laying parental behaviors, combined with direct exposure
      of embryos to mercury, likely contribute to reduced reproductive success and
      should be considered in future studies. Further research is warranted in field
      settings, where parents are exposed to greater environmental challenges and
      subtle behavioral differences might have more serious consequences than were
      observed in captivity.

PMID- 29022242
TI  - Exploring the Role of YouTube in Disseminating Psychoeducation.
AB  - OBJECTIVE: Social media can bridge the gap between health care and ethnic
      minorities over cultural barriers. This study explores the role of YouTube in
      delivering schizophrenia education to individuals in the USA who are also fluent
      in Chinese. METHODS: Three psychoeducational YouTube videos related to
      schizophrenia were uploaded. Data were collected for a 12-month period, and
      results were analyzed using descriptive statistics. RESULTS: The videos recorded
      4935 views with a total viewing time of 35,614 min. The first-episode psychosis
      video had the most number of views and shares, and the longest total watch time
      and average view duration. The targeted age group (< 34 years old) comprised
      about half of the total views and had a 14.4% longer average view duration
      compared to the overall average. CONCLUSION: YouTube is a useful tool that
      delivers schizophrenia education to Chinese-speaking individuals in the USA. It
      may also help alleviate the negative stigma regarding schizophrenia and other
      mental health issues.

PMID- 29022241
TI  - A panel of protein candidates for comprehensive study of Caprine Arthritis
      Encephalitis (CAE) infection.
AB  - The caprine arthrite encephalite (CAE) is a disease that affects especially dairy
      goat. The virus shows compartmentalization features, that allows it to hide at
      certain times during the course of the disease, making it difficult to control.
      The present study was conducted to identify the major seminal plasma protein
      profile of goats infected by CAE and its associations with seroconversion using
      Western blotting. Two groups containing five males each, were used in this
      experiment. The first group was composed by seropositive animals and the control
      by seronegative confirmed by Western blotting and PCR. The semen was collected
      through artificial vagina and after that, two-dimensional electrophoresis and
      MALDI-TOF MS were used. Seventy-five spots were identified in the goat seminal
      plasma gels, equivalent to 13 different proteins with more expression. The
      similar proteins found in both groups and related to reproduction were
      spermadhesin Z13-like, bodhesin and bodhesin-2, Lipocalin, protein PDC-109-like,
      and albumin. In infected goats, proteases such as arisulfatase A have been
      identified, whose function probably is related to metabolism control of
      sulfatides, involved to virus control. The other ones were bifunctional ATP
      dependent dihydroxyacetone kinase/FAD-AMP lyase, cathepsin F isoform X1,
      disintegrin and metalloproteinase domain-containing protein 2-like isoform X1,
      clusterin, carbonic anhydrase 2, electron transfer flavoprotein subunit beta, and
      epididymal secretory glutathione peroxidase. The results of this study show the
      reaction of the innate immune system against chronic infection of goats by CAE.

PMID- 29022244
TI  - Systemic embolism from bilateral atrial myxomas.

PMID- 29022243
TI  - Pyrosequencing analysis of source water switch and sulfate-induced bacterial
      community transformation in simulated drinking water distribution pipes.
AB  - Inter-basin water transfer and source water switching will be increasingly
      launched due to significant population increase and the shortage of the local
      water resources in cities around the world. Source water switch may cause
      physiochemical and microbiological de-stabilization of pipe material, biofilms,
      and loose deposits in drinking water distribution system (DWDS). Great sulfate
      alteration during source water switch had been deemed as the main cause of a red
      water case that occurred in a northern China city. To ascertain the relationship
      between water quality changing and bacterial communities of biofilms in DWDS and
      possible bacteria risk in a red water case, water quality changing experiments in
      simulated DWDSs were conducted for approximately 2 years. Twenty-five corrosion
      scale samples and eight water samples collected from pipe harvest sites or during
      experimental periods were analyzed for their bacterial community composition by
      454-pyrosequencing technology. Taxonomy results together with redundancy analysis
      (RDA) or canonical correspondence analysis (CCA) and hierarchical cluster
      analysis all indicated that bacterial community of samples with groundwater (GW)
      or surface water (SW) supply history and their variations under high sulfate
      water were rather different owing to different water source histories and the
      original pipe scale characteristics. Potential opportunistic pathogens:
      Burkholderia, Escherichia-Shigella, Mycobacterium, Serratia, Ralstonia,
      Novosphingobium, Flavobacterium, Sphingomonas, and Sphingopyxis were observed in
      scale or water samples.

PMID- 29022245
TI  - Prevalence of eosinophilic esophagitis in patients with gastroesophageal reflux
      symptoms: A cross-sectional study from a tertiary care hospital in North India.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is being recognized increasingly all
      over the globe; Indian data is however sparse. We screened patients with symptoms
      of gastroesophageal reflux disease (GERD) for presence of EoE in them. METHODS:
      Consecutive patients with symptoms suggestive of GERD underwent
      gastroduodenoscopy and esophageal biopsies, obtained from both the upper
      esophagus (5 cm below the upper esophageal sphincter) and lower esophagus (5 cm
      above gastroesophageal junction), as well as from any other endoscopically
      visible abnormal mucosa. Demographic and clinical characteristics, endoscopic
      findings, peripheral blood eosinophilic count, and history of use of proton-pump
      inhibitors (PPIs) were analyzed. Stool examination was done to rule out
      parasitoids. EoE was diagnosed if number of mucosal eosinophil infiltrate was >20
      per high-power field. In the latter, Warthin-Starry stain was performed to rule
      out presence of H elicobacter pylori. RESULTS: Of 190 consecutive patients with
      symptoms of GERD screened, esophageal biopsies were available in 185 cases. Of
      them, 6 had EoE, suggesting a prevalence of 3.2% among patients with GERD. On
      univariate analysis, history of allergy, non-response to PPI, and absolute
      eosinophil counts and on multivariable analysis, history of allergy and no
      response to PPIs were significant predictors of EoE. Presence of EOE did not
      correlate with severity of reflux symptoms. CONCLUSION: In this hospital-based
      study from northern part of India, prevalence of EoE in patients with GERD was
      3.2%. EoE should be considered as a diagnostic possibility, especially in those
      with history of allergy, no-response to PPI, and absolute eosinophil count of
      >=250/cumm.

PMID- 29022246
TI  - Alpha-lipoic acid mitigates toxic-induced demyelination in the corpus callosum by
      lessening of oxidative stress and stimulation of polydendrocytes proliferation.
AB  - Multiple Sclerosis (MS), is a disease that degenerates myelin in central nervous
      system (CNS). Reactive oxygen species (ROSs) are toxic metabolites, and
      accumulating data indicate that ROSs-mediated apoptosis of oligodendrocytes
      (OLGs) plays a major role in the pathogenesis of MS under oxidative stress
      conditions. In this study, we investigated the role of endogenous antioxidant
      alpha-lipoic acid (ALA) as ROSs scavenger in the OLGs loss and myelin
      degeneration during cuprizone (cup)-induced demyelination in the experimental
      model of MS. Our results have shown that ALA treatment significantly increased
      population of mature OLGs (MOG+ cells), as well as decreased oxidative stress
      (ROSs, COX-2 and PGE2) and apoptosis mediators (caspase-3 and Bax/Bcl2 ratio) in
      corpus callosum (CC). Surprisingly, ALA significantly stimulates population of
      NG2 chondroitin sulfate proteoglycan positive glia (NG2+ cells or
      polydendrocytes), from week 4 afterward. Accordingly ALA could prevents
      apoptosis, delays demyelination and recruits OLGs survival and regeneration
      mechanisms in CC. We conclude that ALA has protective effects against toxic
      demyelination via reduction of redox signaling, and alleviation of
      polydendrocytes vulnerability to excitotoxic challenge.

PMID- 29022247
TI  - Persistent Norovirus Contamination of Groundwater Supplies in Two Waterborne
      Outbreaks.
AB  - Microbiological contamination of groundwater supplies causes waterborne outbreaks
      worldwide. In this study, two waterborne outbreaks related to microbiological
      contamination of groundwater supplies are described. Analyses of pathogenic human
      enteric viruses (noroviruses and adenoviruses), fecal bacteria (Campylobacter
      spp. and Salmonella spp.), and indicator microbes (E. coli, coliform bacteria,
      intestinal enterococci, Clostridium perfringens, heterotrophic plate count,
      somatic and F-specific coliphages) were conducted in order to reveal the cause of
      the outbreaks and to examine the effectiveness of the implemented management
      measures. Moreover, the long-term persistence of noro- and adenovirus genomes was
      investigated. Noroviruses were detected in water samples from both outbreaks
      after the intrusion of wastewater into the drinking water sources. In the
      outbreak I, the removal efficiency of norovirus genome (3.0 log10 removal) in the
      sand filter of onsite wastewater treatment system (OWTS) and during the transport
      through the soil into the groundwater well was lower than the removal
      efficiencies of E. coli, coliform bacteria, intestinal enterococci, and spores of
      C. perfringens (6.2, 6.0, > 5.9, and > 4.8 log10 removals, respectively). In the
      outbreak II, cleaning of massively contaminated groundwater well and drinking
      water distribution network proved challenging, and noro- and adenovirus genomes
      were detected up to 3 months (108 days). The long-term persistence study showed
      that noro- and adenovirus genomes can remain detectable in the contaminated water
      samples up to 1277 and 1343 days, respectively. This study highlights the
      transport and survival properties of enteric viruses in the environment
      explaining their potency to cause waterborne outbreaks.

PMID- 29022249
TI  - Common Subcluster Mining in Microarray Data for Molecular Biomarker Discovery.
AB  - Molecular biomarkers can be potential facilitators for detection of cancer at
      early stage which is otherwise difficult through conventional biomarkers. Gene
      expression data from microarray experiments on both normal and diseased cell
      samples provide enormous scope to explore genetic relations of disease using
      computational techniques. Varied patterns of expressions of thousands of genes at
      different cell conditions along with inherent experimental error make the task of
      isolating disease related genes challenging. In this paper, we present a data
      mining method, common subcluster mining (CSM), to discover highly perturbed genes
      under diseased condition from differential expression patterns. The method builds
      heap through superposing near centroid clusters from gene expression data of
      normal samples and extracts its core part. It, thus, isolates genes exhibiting
      the most stable state across normal samples and constitute a reference set for
      each centroid. It performs the same operation on datasets from corresponding
      diseased samples and isolates the genes showing drastic changes in their
      expression patterns. The method thus finds the disease-sensitive genesets when
      applied to datasets of lung cancer, prostrate cancer, pancreatic cancer, breast
      cancer, leukemia and pulmonary arterial hypertension. In majority of the cases,
      few new genes are found over and above some previously reported ones. Genes with
      distinct deviations in diseased samples are prospective candidates for molecular
      biomarkers of the respective disease.

PMID- 29022248
TI  - Coxsackievirus B4 as a Causative Agent of Diabetes Mellitus Type 1: Is There a
      Role of Inefficiently Treated Drinking Water and Sewage in Virus Spreading?
AB  - This study proposed to detect the enterovirus (EV) infection in children with
      type 1 diabetes mellitus (T1D) and to assess the role of insufficiently treated
      water and sewage as sources of viral spreading. Three hundred and eighty-two
      serum specimens of children with T1D, one hundred serum specimens of children who
      did not suffer from T1D as control, and forty-eight water and sewage samples were
      screened for EV RNA using nested RT-PCR. The number of genome copies and
      infectious units of EVs in raw and treated sewage and water samples were
      investigated using real-time (RT)-PCR and plaque assay, respectively. T1D markers
      [Fasting blood glucose (FBG), HbA1c, and C-peptide], in addition to anti
      Coxsackie A & B viruses (CVs A & B) IgG, were measured in control, T1D-negative
      EV (T1D-EV-), and T1D-positive EV (T1D-EV+) children specimens. The prevalence of
      EV genome was significantly higher in diabetic children (26.2%, 100 out of 382)
      than the control children (0%, 0 out of 100). FBG and HbA1c in T1D-EV- and T1D
      EV+ children specimens were significantly higher than those in the control group,
      while c-peptide in T1D-EV- and T1D-EV+ children specimens was significantly lower
      than that in the control (n = 100; p < 0.001). Positivity of anti-CVs A & B IgG
      was 70.7, 6.7, and 22.9% in T1D-EV+, T1D-EV-, and control children specimens,
      respectively. The prevalence of EV genome in drinking water and treated sewage
      samples was 25 and 33.3%, respectively. The prevalence of EV infectious units in
      drinking water and treated sewage samples was 8.5 and 25%, respectively.
      Quantification assays were performed to assess the capabilities of both
      wastewater treatment plants (WWTPs) and water treatment plants (WTPs) to remove
      EV. The reduction of EV genome in Zenin WWTP ranged from 2 to 4 log10, while the
      reduction of EV infectious units ranged from 1 to 4 log10. The reduction of EV
      genome in El-Giza WTP ranged from 1 to 3 log10, while the reduction of EV
      infectious units ranged from 1 to 2 log10. This capability of reduction did not
      prevent the appearance of infectious EV in treated sewage and drinking water.
      Plaque purification was performed for isolation of separate EV isolates from
      treated and untreated water and sewage samples. Characterization of the EV
      amplicons by RT-PCR followed by sequencing of these isolates revealed high
      homology (97%) with human coxsackievirus B4 (CV B4) in 60% of the isolates, while
      the rest of the isolates belonged to poliovirus type 1 and type 2 vaccine
      strains. On the other hand, characterization of the EV amplicons by RT-PCR
      followed by sequencing for T1D-EV+ children specimens indicated that all samples
      contained CV B4 with the same sequence characterized in the environmental
      samples. CV B4-contaminated drinking water or treated sewage may play a role as a
      causative agent of T1D in children.

PMID- 29022250
TI  - Fundamental Limits of Forced Asynchronous Spiking with Integrate and Fire
      Dynamics.

PMID- 29022251
TI  - Genetic and environmental relationships between eating behavior and symptoms of
      anxiety and depression.
AB  - PURPOSE: To assess gender-specific genetic and environmental correlations between
      depressive and anxiety symptoms, and concurrent and follow-up eating behavior in
      Korean twins and their family members. METHODS: Center for Epidemiological
      Studies Depression Scale and State-Trait Anxiety Inventory were used to measure
      depressive and anxiety symptoms in subjects. To assess concurrent and follow-up
      relationships of the symptoms with eating behavior domains (restrained,
      emotional, and external eating), the Dutch Eating Behavior Questionnaire was
      administered to 2359 subjects at baseline (men, 48.5%; 42.0 +/- 12.7 years;
      monozygotic twins, 33.7%) and to 1169 subjects at follow-up (men, 45.9%; 44.9 +/-
      11.6 years; monozygotic twins, 41.0%). A mixed linear model and bivariate
      analysis were applied. RESULTS: After adjusting for age, twin and family effects,
      income, education, smoking status, alcohol use, exercise, and body mass index,
      depressive and anxiety symptoms were positively associated with concurrent and
      follow-up emotional and external eating, but not with restrained eating. The
      effect size of association with emotional eating increased in men in men over
      time, but decreased in women. Common genetic and environmental correlations
      showed a difference between genders, and their strength changed with time.
      Nevertheless, common genetic correlations were found between depressive and
      anxiety symptoms, and concurrent emotional eating, in both genders. There were
      common environmental correlations between anxiety symptoms, and concurrent
      restrained and emotional as well as follow-up emotional eating, in both genders.
      CONCLUSIONS: There are similarities and differences in genetic and environmental
      relationships between depressive and anxiety symptoms and eating behaviors, based
      on gender and time of assessment. LEVEL OF EVIDENCE: Level III, cohort study.

PMID- 29022252
TI  - Biological Data on Anovia punica Gordon (Coleoptera: Coccinellidae), a Predator
      of Crypticerya multicicatrices Kondo & Unruh (Hemiptera: Monophlebidae).
AB  - The coccinellid beetle Anovia punica Gordon (Coleoptera: Coccinellidae: Noviini)
      is an important predator of the Colombian fluted scale, Crypticerya
      multicicatrices Kondo & Unruh (Hemiptera: Monophlebidae). In order to gather
      information on the biological traits of A. punica, we conducted a series of
      studies, including of the developmental time of each life history stage,
      estimation of life table parameters, and predation rates under laboratory
      conditions [25.1 +/- 1.6 degrees C, with 70.5 +/- 7.3% RH, and natural light
      regime, approx. 12:12 (L:D) h]. Developmental stages of A. punica were
      categorized as follows: egg stage, four larval instars, prepupal instar, pupal
      instar, and adult. Developmental time from egg to adult emergence averaged 29.41
      +/- 1.85 days, and 47.6% of the eggs developed to adulthood. Female and male
      survival was 94.42 and 90 days, respectively. Life table parameters show that one
      female of A. punica is replaced by 86 females (R 0), the intrinsic growth rate (r
      m ) was 0.1115, the average generation time (T) was 40 days, and the doubling
      time (D t ) was 6.2 days. The life table parameters suggest that A. punica can be
      used as a potential predator of C. multicicatrices and, more importantly,
      provided baseline information for a mass-rearing protocol. This is the first
      detailed study on the biology of A. punica that reports the potential of this
      predator as a biological control agent for scale insects of the tribe Iceryini.

PMID- 29022253
TI  - Successful transcatheter aortic valve implantation in a quadricuspid aortic valve
      with severe stenosis and moderate regurgitation.

PMID- 29022254
TI  - Physical Inactivity and the Economic and Health Burdens Due to Cardiovascular
      Disease: Exercise as Medicine.
AB  - Leisure time physical activity, or exercise, has been described as today's best
      buy in public health. Physical inactivity is responsible for around 10% of all
      deaths and physical inactivity costs global healthcare systems billions of
      dollars each year. Here, we describe the human and economic costs of
      cardiovascular disease. Then, we explain that physical inactivity is a major
      modifiable risk factor for cardiovascular disease. The evidence of the role of
      physical activity in the primary prevention of cardiovascular disease is reviewed
      and we make the case that exercise is medicine.

PMID- 29022255
TI  - Acute and Chronic Response to Exercise in Athletes: The "Supernormal Heart".
AB  - During last decades, most studies have examined the exercise-induced remodeling
      defined as "athlete's heart". During exercise, there is an increased cardiac
      output that causes morphological, functional, and electrical modification of the
      cardiac chambers. The cardiac remodeling depends also on the type of training,
      age, sex, ethnicity, genetic factors, and body size. The two main categories of
      exercise, endurance and strength, determine different effects on the cardiac
      remodeling. Even if most sport comprise both strength and endurance exercise,
      determining different scenarios of cardiac adaptation to the exercise. The aim of
      this paper is to assemble the current knowledge about physiologic and
      pathophysiologic response of both the left and the right heart in highly trained
      athletes.

PMID- 29022256
TI  - The Effects of Exercise on Cardiovascular Biomarkers: New Insights, Recent Data,
      and Applications.
AB  - The benefit of regular exercise or physical activity with appropriate intensity
      on improving cardiopulmonary function and endurance has long been accepted with
      less controversy. The challenge remains, however, quantitatively evaluate the
      effect of exercise on cardiovascular health due in part to the amount and
      intensity of exercise varies widely plus lack of effective, robust and efficient
      biomarker evaluation systems. Better evaluating the overall function of biomarker
      and validate biomarkers utility in cardiovascular health should improve the
      evidence regarding the benefit or the effect of exercise or physical activity on
      cardiovascular health, in turn increasing the efficiency of the biomarker on
      individuals with mild to moderate cardiovascular risk. In this review, beyond
      traditional cytokines, chemokines and inflammatory factors, we systemic reviewed
      the latest novel biomarkers in metabolomics, genomics, proteomics, and molecular
      imaging mainly focus on heart health, as well as cardiovascular diseases such as
      atherosclerosis and ischemic heart disease. Furthermore, we highlight the state
      of-the-art biomarker developing techniques and its application in the field of
      heart health. Finally, we discuss the clinical relevance of physical activity and
      exercise on key biomarkers in molecular basis and practical considerations.

PMID- 29022258
TI  - Structural, Contractile and Electrophysiological Adaptations of Cardiomyocytes to
      Chronic Exercise.
AB  - Cardiac beneficial effects of chronic exercise is well admitted. These effects
      mainly studied at the organ and organism integrated levels find their origin in
      cardiomyocyte adaptation. This chapter try to highlight the main trends of the
      data related to the different parameters subject to such adaptations. This is
      addressed through cardiomyocytes size and structure, calcium and contractile
      properties, and finally electrophysiological alterations induced by training as
      they transpire from the literature. Despite the clarifications needed to decipher
      healthy cardiomyocyte remodeling, this overview clearly show that cardiac cell
      plasticity ensure the cardiac adaptation to exercise training and offers an
      interesting mean of action to counteract physiological disturbances induced by
      cardiac pathologies.

PMID- 29022257
TI  - Acute and Chronic Exercise in Animal Models.
AB  - Numerous animal cardiac exercise models using animal subjects have been
      established to uncover the cardiovascular physiological mechanism of exercise or
      to determine the effects of exercise on cardiovascular health and disease. In
      most cases, animal-based cardiovascular exercise modalities include treadmill
      running, swimming, and voluntary wheel running with a series of intensities,
      times, and durations. Those used animals include small rodents (e.g., mice and
      rats) and large animals (e.g., rabbits, dogs, goats, sheep, pigs, and horses).
      Depending on the research goal, each experimental protocol should also describe
      whether its respective exercise treatment can produce the anticipated acute or
      chronic cardiovascular adaptive response. In this chapter, we will briefly
      describe the most common kinds of animal models of acute and chronic
      cardiovascular exercises that are currently being conducted and are likely to be
      chosen in the near future. Strengths and weakness of animal-based cardiac
      exercise modalities are also discussed.

PMID- 29022259
TI  - Formation of New Cardiomyocytes in Exercise.
AB  - Heart failure is a life-threatening disorder associated with the loss of
      cardiomyocytes. The heart has some endogenous although limited regenerative
      capacity, thus enhancing cardiac regeneration or stimulating endogenous repair
      mechanism after cardiac injury is of great interest. The benefits of exercise in
      heart diseases have been recognized for centuries. Besides the promotion of a
      favorable cardiac function, exercise is also associated with new cardiomyocytes
      formation. Exercise may lead to cardiomyocytes renewal from pre-existing
      cardiomyocytes proliferation or cardiac stem/progenitor cells differentiation. A
      deep understanding of exercise-induced formation of new cardiomyocytes will
      enable us to develop novel therapeutics for heart diseases.

PMID- 29022260
TI  - Physical Exercise Can Spur Beneficial Neoangiogenesis and Microvasculature
      Remodeling Within the Heart - Our Salvation?
AB  - Economic and social burden of cardiovascular diseases remains enormous and even
      still rising. There is not enough mass evidence in scientific journals that could
      describe the course of the process of neoangiogenesis in relatively "healthy"
      heart after regular endurance exercise. Even though, in this review, we are
      showing preliminary evidence that this can be one of really cheap and effective
      preventive means. We are elucidating some of the cellular signaling pathways how
      exercise could affect neoangiogenesis and ameliorate performance of the heart.
      Key roles in this process are mechanical forces (mainly increased velocity of
      blood flow and shear stress) and subsequent rise of angiogenic biological factors
      (mainly VEGFA).

PMID- 29022261
TI  - The Non-cardiomyocyte Cells of the Heart. Their Possible Roles in Exercise
      Induced Cardiac Regeneration and Remodeling.
AB  - The non-cardiomyocyte cellular microenvironment of the heart includes diverse
      types of cells of mesenchymal origin. During development, the majority of these
      cells derive from the epicardium, while a subset derives from the
      endothelium/endocardium and neural crest derived mesenchyme. This subset includes
      cardiac fibroblasts and telocytes, the latter of which are a controversial type
      of "connecting cell" that support resident cardiac progenitors in the postnatal
      heart. Smooth muscle cells, pericytes, and endothelial cells are also present, in
      addition to adipocytes, which accumulate as epicardial adipose connective tissue.
      Furthermore, the heart harbors many cells of hematopoietic origin, such as mast
      cells, macrophages, and other immune cell populations. Most of these control
      immune reactions and inflammation. All of the above-mentioned non-cardiomyocyte
      cells of the heart contribute to this organ's well-orchestrated physiology. These
      cells also contribute to regeneration as a result of injury or age, in addition
      to tissue remodeling triggered by chronic disease or increased physical activity
      (exercise-induced cardiac growth). These processes in the heart, the most
      important vital organ in the human body, are not only fascinating from a
      scientific standpoint, but they are also clinically important. It is well-known
      that regular exercise can help prevent many cardiovascular diseases. However, the
      precise mechanisms underpinning myocardial remodeling triggered by physical
      activity are still unknown. Surprisingly, exercise-induced adaptation mechanisms
      are often identical or very similar to tissue remodeling caused by pathological
      conditions, such as hypertension, cardiac hypertrophy, and cardiac fibrosis. This
      review provides a summary of our current knowledge regarding the cardiac cellular
      microenvironment, focusing on the clinical applications this information to the
      study of heart remodeling during regular physical exercise.

PMID- 29022262
TI  - Myocardial Infarction and Exercise Training: Evidence from Basic Science.
AB  - In 2016, cardiovascular disease remains the first cause of mortality worldwide
      [1]. Coronary artery disease, which is the most important precursor of myocardial
      infarction (MI), is the main component of total cardiovascular mortality, being
      responsible for approximately seven million of deaths [1]. In approximately 20%
      of infarcted patients, MI is recurrent in the first year after the event [2].
      Moreover, among cardiovascular disease, coronary artery disease accounts for the
      most increased index of life years lost due to morbidity and/or mortality [1].
      Sedentarism highly contributes to cardiovascular disease burden, especially for
      coronary artery disease, and is also one of the MI risk factors [3]. For many
      years, it was recommended to avoid physical activity after a cardiovascular
      event; nowadays, it is a consensus that exercise training (ET) should be part of
      cardiac rehabilitation programs. There is increasing evidence confirming that,
      when adequately prescribed and supervised, ET after MI can prevent future
      complications and increase the quality of life and longevity of infarcted
      patients [4, 5]. ET after MI follows international specialized guidelines;
      however, there are different protocols adopted by several societies worldwide in
      cardiac rehabilitation [6], and there is still lack of information on which type
      and regimen of exercise may be the ideal after MI, as well as how these exercises
      act to promote beneficial effects to cardiovascular and other organic systems.
      Thus, experimental studies are important contributors to elicit mechanisms behind
      clinical results, and to test and compare different ET protocols. Therefore,
      exercise prescription can be optimized, individualized, and safely practiced by
      patients. In this chapter, we present a brief review of MI pathophysiology
      followed by an updated discussion of the most relevant discoveries regarding ET
      and MI in basic science.

PMID- 29022263
TI  - Cardiac Ischemia/Reperfusion Injury: The Beneficial Effects of Exercise.
AB  - Cardiac ischemia reperfusion injury (IRI) occurs when the myocardium is
      revascularized after an episode of limited or absent blood supply. Many changes,
      including free radical production, calcium overload, protease activation, altered
      membrane lipids and leukocyte activation, contribute to IRI-induced myocardium
      damage. Aerobic exercise is the only countermeasure against IRI that can be
      sustained on a regular basis in clinical practice. Interestingly, both short-term
      (3-5 days) and long-term (several weeks) exercise increase myocardial tolerance,
      reduce infarct size area and arrhythmias induced by IRI. Exercise protects the
      heart against IRI in a biphasic manner. The early phase of cardioprotection
      occurs between 30 min and 3 h following an acute exercise bout, whilst the late
      phase is achieved within 24 h after the exercise bout and persists for several
      days. As for the exercise intensity, although controversial data exists, it is
      feasible that the amount of cardioprotection is proportional to exercise
      intensity and only achieved above a critical threshold. It is known that aerobic
      exercise produces a cardioprotective phenotype, however the mechanisms
      responsible for this phenomenon remain unclear. Apparently, aerobic exercise
      induced preconditioning is dependent on several factors that work together to
      protect the heart. Altered nitric oxide (NO) signaling, increased levels of heat
      shock proteins (HSPs), enhanced function of ATP-sensitive potassium channels,
      increased activation of opioids system, and enhanced antioxidant capacity may
      contribute to exercise-induced cardioprotection. Much has been discovered from
      animal models involving exercise-induced cardioprotection against cardiac IRI,
      however translating these findings to clinical practice still represents the
      major challenge in this field.

PMID- 29022264
TI  - Experimental Evidences Supporting the Benefits of Exercise Training in Heart
      Failure.
AB  - Heart Failure (HF), a common end point for many cardiovascular diseases, is a
      syndrome with a very poor prognosis. Although clinical trials in HF have achieved
      important outcomes in reducing mortality, little is known about functional
      mechanisms conditioning health improvement in HF patients. In parallel with
      clinical studies, basic science has been providing important discoveries to
      understand the mechanisms underlying the pathophysiology of HF, as well as to
      identify potential targets for the treatment of this syndrome. In spite of being
      the end-point of cardiovascular derangements caused by different etiologies,
      autonomic dysfunction, sympathetic hyperactivity, oxidative stress, inflammation
      and hormonal activation are common factors involved in the progression of this
      syndrome. Together these causal factors create a closed link between three
      important organs: brain, heart and the skeletal muscle. In the past few years, we
      and other groups have studied the beneficial effects of aerobic exercise training
      as a safe therapy to avoid the progression of HF. As summarized in this chapter,
      exercise training, a non-pharmacological tool without side effects, corrects most
      of the HF-induced neurohormonal and local dysfunctions within the brain, heart
      and skeletal muscles. These adaptive responses reverse oxidative stress, reduce
      inflammation, ameliorate neurohormonal control and improve both cardiovascular
      and skeletal muscle function, thus increasing the quality of life and reducing
      patients' morbimortality.

PMID- 29022265
TI  - Exercise Amaliorates Metabolic Disturbances and Oxidative Stress in Diabetic
      Cardiomyopathy: Possible Underlying Mechanisms.
AB  - Cardiomyopathy is a serious complication of diabetes mellitus and occurs
      independently of coronary artery disease or hypertension. It manifests as
      systolic/diastolic dysfunction and hypertrophy of the left ventricle and can lead
      to heart failure. Hyperglycemia can trigger a series of maladaptive stimuli and
      result in cardiac hypertrophy, fibrosis and reduced performance and
      contractility. The pathogenesis of diabetic cardiomyopathy is a multifactorial
      process that includes metabolic derangements such as increased oxidative stress,
      and altered non-oxidative glucose pathways and lipid metabolism. Exercise is a
      useful non-pharmacological strategy effective in the reduction of diabetes and
      obesity risk factors, and improvement of antioxidant defenses, mitochondrial
      function and physiological cardiac growth. It can amend multiple metabolic
      derangements and alterations in the diabetic heart. Therefore, figuring out the
      underlying mechanisms of exercise-induced beneficial effects could help to
      develop new treatment strategies for diabetic cardiomyopathy.

PMID- 29022266
TI  - Cardiac Aging - Benefits of Exercise, Nrf2 Activation and Antioxidant Signaling.
AB  - Cardiovascular dysfunction and heart failure associated with aging not only
      impairs the cardiac function but also the quality of life eventually decreasing
      the life expectancy of the elderly. Notably, cardiac tissue can prematurely age
      under certain conditions such as genetic mutation, persistent redox stress and
      overload, aberrant molecular signaling, DNA damage, telomere attrition, and other
      pathological insults. While cardiovascular-related morbidity and mortality is on
      the rise and remains a global health threat, there has been only little to
      moderate improvements in its medical management. This is due to the fact that the
      lifestyle changes to molecular mechanisms underlying age-related myocardial
      structure and functional remodeling are multifactorial and intricately operate at
      different levels. Along these lines, the intrinsic redox mechanisms and oxidative
      stress (OS) are widely studied in the myocardium. The accumulation of reactive
      oxygen species (ROS) with age and the resultant oxidative damage has been shown
      to increase the susceptibility of the myocardium to multiple complications such
      as atherosclerosis, hypertension, ischemic heart disease, cardiac myopathy, and
      heart failure. There has been growing interest in trying to enhance the
      mechanisms that neutralize the ROS and curtailing OS as a possible anti-aging
      intervention and as a treatment for age-related disorders. Natural defense system
      to fight against OS involves a master transcription factor named nuclear
      erythroid-2-p45-related factor-2 (Nrf2) that regulates several antioxidant genes.
      Compelling evidence exists on the Nrf2 gain of function through pharmacological
      interventions in counteracting the oxidative damage and affords cytoprotection in
      several organs including but not limited to lung, liver, kidney, brain, etc.
      Nevertheless, thus far, only a few studies have described the potential role of
      Nrf2 and its non-pharmacological induction in cardiac aging. This chapter
      explores the effects of various modes of exercise on Nrf2 signaling along with
      its responses and ramifications on the cascade of OS in the aging heart.

PMID- 29022268
TI  - Physical Exercise Is a Potential "Medicine" for Atherosclerosis.
AB  - Cardiovascular disease (CVD) has been recognized as the number one killer for
      decades. The most well-known risk factor is atherosclerosis. Unlike the acuity of
      CVD, atherosclerosis is a chronic, progressive pathological change. This process
      involves inflammatory response, oxidative reaction, macrophage activity, and
      different interaction of inflammatory factors. Physical exercise has long been
      known as good for health in general. In recent studies, physical exercise has
      been demonstrated to be a therapeutic tool for atherosclerosis. However, its
      therapeutic effect has dosage-dependent effect. Un-proper over exercise might
      also cause damage to the heart. Here we summarize the mechanism of Physical
      exercise's beneficial effects and its potential clinical use.

PMID- 29022267
TI  - Cardiac Fibrosis: The Beneficial Effects of Exercise in Cardiac Fibrosis.
AB  - Numerous scientific findings have concluded that individuals who are active tend
      to develop less cardiovascular disease than those who enjoy more sedentary
      lifestyles. Animal models have further demonstrated that the beneficial effects
      of training on the heart effects of training are related to the signaling
      pathways of myocardial hypertrophy and fibrosis. As such, fibroblasts represent a
      very important population of cells within the myocardium as they play a crucial
      role in both cardiac development and response to injury. Fibroblasts establish
      and maintain the biochemical, electrical and mechanical environment of the heart
      through their complex interactions with cardiomyocytes. Cardiac injury disrupts
      the balance between fibroblasts and cardiomyocytes and creates a state favouring
      inflammation and fibrosis. Although this adaptive response initially serves to
      increase wound healing, it may eventually lead to increased cardiac damage and
      cardiac failure if homeostasis is not restored. Myofibroblasts are mediators of
      both the adaptive and maladaptive components of this reaction. This review
      focuses on the beneficial effects of exercise in cardiac fibrosis as demonstrated
      in basic research studies. Attention will be given to the characterisation of the
      relationship between exercise and cardiac remodelling, including the cellular and
      molecular adaptations of the heart in response to exercise as well as benefits of
      exercise in preventing or reversing the pathological remodelling of the fibrotic
      heart. By furthering our understanding of the beneficial and deleterious roles of
      cardiac fibroblasts and myofibroblasts and how these roles are related to each
      other in cardiac development and in heart disease, we may be able to design
      interventions to prevent the progression of cardiac fibrosis.

PMID- 29022269
TI  - Experimental Evidences Supporting Training-Induced Benefits in Spontaneously
      Hypertensive Rats.
AB  - It is well known that chronic hypertension is accompanied by several functional
      deficits in the central nervous system and peripheral tissues, most of which are
      corrected by exercise training. However, the biological mechanisms underlying
      these effects are not yet well understood. In the present chapter we summarize
      recent experimental evidence on cellular/molecular mechanisms supporting not only
      the deleterious effects of hypertension on autonomic control and peripheral
      circulatory deficits, but also their reversion by low to moderate aerobic
      exercise training. Interestingly, both hypertension and aerobic training exert
      their effects by acting exactly on the same pathways/mechanisms but in opposed
      directions.

PMID- 29022270
TI  - Exercise Training in Pulmonary Hypertension and Right Heart Failure: Insights
      from Pre-clinical Studies.
AB  - Exercise training (ExT) is widely used for the prevention and treatment of
      several chronic cardiovascular diseases. However, only recently it started to be
      recognized as safe and beneficial in pulmonary arterial hypertension. Despite the
      consistency of its favorable effects on exercise tolerance and quality of life,
      the mechanisms underlying these meaningful clinical improvements remain unclear.
      Current studies emphasize the exercise-induced changes on skeletal muscle but the
      impact of ExT at the level of the pulmonary circulation and right ventricle
      should not be overlooked. In this chapter, we summarize the main findings from
      pre-clinical studies analyzing the impact of exercise in pulmonary hypertension
      and right heart failure.

PMID- 29022271
TI  - A comparison of six clock-drawing test scoring methods in a nursing home.
AB  - BACKGROUND: Clock-drawing test (CDT) is widely used but lack of a suitable
      scoring method. AIMS: To compare the validity of six common CDT scoring methods
      and to find out the best one. METHODS: The drawing CDT was administered in a
      Chinese nursing-home inhabitants living on the mainland including 110 dementia,
      118 MCI (mild cognitive impairment), and 133 random normal. We calculated the
      sensitivity and specificity of six scoring methods and applied the receiver
      operating characteristic (ROC) curve statistic, including determining the area
      under the curve (AUC). RESULTS: (1) All six CDT scoring methods had a value of
      sensitivity higher than 80% and a specificity of 60% except Jouk and Tuokko.
      Freund got the highest sensitivity (92.73%) of that five for the testing of
      dementia and high sensitivity (82.20%) for MCI with an acceptable specificity
      (70.68%). (2) The AUC (area under the ROC curve) of all six CDT methods was over
      0.8 for dementia, and for MCI, only Jouk and Tuokko were lower than 0.8. Mendez
      had the largest AUC of 0.872 for MCI, which closely followed by Freund with
      0.859. (3) Freund predicted dementia best but had no significant difference (p >
      0.05); it only had significant difference with Jouk and Tuokko (p < 0.001) and
      the method in MoCA (p < 0.05) for both MCI and cognitive impairment. CONCLUSIONS:
      Our study suggests that Freund scoring method could be the best one among the six
      evaluated scoring methods within our setting.

PMID- 29022272
TI  - Analysis and experimental evaluation of shunt active power filter for power
      quality improvement based on predictive direct power control.
AB  - This paper discusses the use of the concept of classical and predictive direct
      power control for shunt active power filter function. These strategies are used
      to improve the active power filter performance by compensation of the reactive
      power and the elimination of the harmonic currents drawn by non-linear loads. A
      theoretical analysis followed by a simulation using MATLAB/Simulink software for
      the studied techniques has been established. Moreover, two test benches have been
      carried out using the dSPACE card 1104 for the classic and predictive DPC control
      to evaluate the studied methods in real time. Obtained results are presented and
      compared in this paper to confirm the superiority of the predictive technique. To
      overcome the pollution problems caused by the consumption of fossil fuels,
      renewable energies are the alternatives recommended to ensure green energy. In
      the same context, the tested predictive filter can easily be supplied by a
      renewable energy source that will give its impact to enhance the power quality.

PMID- 29022273
TI  - Staphylococcus lugdunensis Infections of the Skin and Soft Tissue: A Case Series
      and Review.
AB  - INTRODUCTION: Staphylococcus lugdunensis (S. lugdunensis) is a coagulase
      negative, Gram-positive bacterium that can be isolated as a component of normal
      skin flora in humans. However, more recently, it has also been documented as a
      culprit in skin and soft tissue infections. We describe the clinical features of
      five individuals with S. lugdunensis-associated skin infections. We review the
      characteristics of other patients that were previously described with this
      organism as the causative agent of skin infection. METHODS: Staphylococcus
      lugdunensis was correlated with the development of significant skin and soft
      tissue infections in five patients. The Pubmed database was used to search for
      the following terms: "abscess," "cellulitis," "cutaneous," "lugdunensis,"
      "paronychia," "skin," "soft," "staphylococcus," and "tissue." The relevant and
      reference papers generated by the search were reviewed. RESULTS: One woman and
      four men developed S. lugdunensis-related skin infections from February 19, 2015
      to May 30, 2017. The patients' ages at the onset of the infection ranged from 30
      to 82 years; the median age was 70 years. Four patients were older than 65 years.
      The back was the most common location for the infection, followed by digits. The
      infection presented as cystic lesions with cellulitis or periungual abscesses.
      The lesions were incised or spontaneously ruptured. Patients were empirically
      treated with oral antibiotics; if necessary, the management was adjusted based on
      the culture-derived sensitivities of the organisms. The infections resolved
      within 10-30 days after commencing treatment. CONCLUSION: Staphylococcus
      lugdunensis has previously been considered as a nonpathogenic organism and to be
      a component of normal skin flora. However, S. lugdunensis can result in
      significant skin and soft tissue infections, perhaps more frequently in older
      individuals. Its antibiotic sensitivities appear to be similar to those of
      methicillin-susceptible Staphylococcus aureus.

PMID- 29022274
TI  - Midazolam prevents motor neuronal death from oxidative stress attack mediated by
      JNK-ERK pathway.
AB  - Midazolam is a sedative used by patients with mechanical ventilation. However,
      the potential clinical value is not fully explored. In this report, we made use
      of a neuroblastoma-spinal cord hybrid motor neuron-like cell line NSC34, and
      elucidated the potential role of Midazolam on these cells under the insult of
      oxidative stress. We found the protective effect of Midazolam on motor neurons
      against cytotoxicity induced by the combination of oligomycin A and rotenone
      (O/R) or phenylarsine oxide. The characteristics of apoptosis, such as the ratio
      of TUNEL+ cells or the expression level of cleaved Caspase-3, was decreased by 22
      or 45% in the presence of Midazolam. Furthermore, this effect was correlated with
      the JNK-ERK signaling pathway. Either phosphorylation of ERK or JNK was
      positively or negatively modulated with the treatment of Midazolam in NSC34 cells
      attacked by reactive oxygen species. Meanwhile, inhibition or activation of the
      JNK-ERK pathway regulated the protective effect of Midazolam on NSC34 cells with
      oxidative stress insult. Collectively, this study elucidated a previously
      unidentified clinical effect of Midazolam, and put forward the great promise that
      Midazolam may be considered as a potential candidate to the treatment of motor
      neuron disease.

PMID- 29022276
TI  - Diagnosis and treatment of TSH-secreting adenomas: review of a longtime
      experience in a reference center.
AB  - PURPOSE: TSH-secreting pituitary adenomas are among the less prevalent pituitary
      tumors, corresponding to 0.9-1.5% of all pituitary adenomas in surgical series.
      METHODS: A series of 11 patients with TSH-secreting and cosecreting adenomas
      diagnosed and treated in the last 25 years in a single center is described.
      RESULTS: The mean age at diagnosis was 37 years (range 18-80 years; median 23
      years); the ratio of male-to-female patients was similar (6M:5F). Only three
      patients was the correct diagnosis established shortly after the initial medical
      evaluation. Other four patients were initially diagnosed with other pituitary
      adenomas (prolactinoma, acromegaly, and non-secreting pituitary tumor) and
      another four diagnosed with primary hyperthyroidism. There was a mean diagnostic
      delay of 6.0 years (range 0.5-25 years; median 2 years). Nine patients had
      macroadenomas and two patients had microadenomas. Seven patients underwent
      pituitary surgery which controlled the disease in only two (one micro- and one
      noninvasive macroadenoma). The other treatments were directed to the thyroid
      gland (surgery or 131I radiotherapy), pituitary radiotherapy, and somatostatin
      analog. CONCLUSION: In spite of its relatively straightforward diagnosis, which
      includes clinical/subclinical hyperthyroidism with or without goiter, increased
      free thyroxine and nonsuppressed TSH levels, and pituitary mass, the diagnosis of
      TSH-secreting and cosecreting adenomas was frequently unrecognized and thus much
      delayed. Serum alpha-subunit levels were high in nearly all patients with TSH
      secreting adenomas and useful in excluding other conditions in the differential
      diagnosis. Proper indication and interpretation of simple laboratory tests should
      be emphasized in medical education to improve diagnostic accuracy.

PMID- 29022277
TI  - Teaching Clinical Reasoning with an Example Mnemonic for the Neuropsychiatric
      Syndromes of Traumatic Brain Injury.

PMID- 29022275
TI  - Volume for Muscle Hypertrophy and Health Outcomes: The Most Effective Variable in
      Resistance Training.
AB  - Resistance training is the most effective method to increase muscle mass. It has
      also been shown to promote many health benefits. Although it is deemed safe and
      of clinical relevance for treating and preventing a vast number of diseases, a
      time-efficient and minimal dose of exercise has been the focus of a great number
      of research studies. Similarly, an inverted U-shaped relationship between
      training dose/volume and physiological response has been hypothesized to exist.
      However, the majority of available evidence supports a clear dose-response
      relationship between resistance training volume and physiological responses, such
      as muscle hypertrophy and health outcomes. Additionally, there is a paucity of
      data to support the inverted U-shaped response. Although it may indeed exist, it
      appears to be much more plastic than previously thought. The overarching
      principle argued herein is that volume is the most easily modifiable variable
      that has the most evidenced-based response with important repercussions, be these
      muscle hypertrophy or health-related outcomes.

PMID- 29022278
TI  - Alzheimer Cafe: an approach focused on Alzheimer's patients but with remarkable
      values on the quality of life of their caregivers.
AB  - BACKGROUND: Alzheimer's disease (AD) affects the global quality of life of
      persons who suffer from it and their caregivers, because of the behavioral and
      psychological consequences associated with the pathology and its caring. The
      Alzheimer Cafe (AC) is one example of approach aimed to help persons and
      caregivers deal with their disease. AIM: This is a pilot study focusing on the
      efficacy of AC in relieving caregivers' and persons' burdens due to dementia.
      METHODS: The quality of life of both caregivers and persons who attended the AC
      was compared with the quality of life of those who did not. Basic and
      instrumental daily activities and neuropsychiatric functioning were assessed.
      Caregivers also answered to general well-being and caregiving burden
      questionnaires. The evaluation took place at the beginning of the intervention
      and after 1, 3, 6, 9 and 12 months. RESULTS: Caregivers who joined the AC with
      their persons with dementia showed to have significantly benefited in the daily
      care of persons with dementia, in terms of total well-being, vitality, and
      emotional burden. DISCUSSION: Although improvements were not observed in persons
      with dementia who attended the AC, significant benefits were reported by their
      caregivers, suggesting that the intervention may produce better management of
      social and economic problems and lead to better emotional support. CONCLUSIONS:
      The AC seems to help families of AD persons to better manage the disease, and
      also delay the institutionalization of these persons, which is certainly an
      ambitious goal for an incurable disorder such as Alzheimer's disease.

PMID- 29022280
TI  - Effects of Bilayer Thickness on the Morphological, Optical, and Electrical
      Properties of Al2O3/ZnO Nanolaminates.
AB  - This report mainly focuses on the investigation of morphological, optical, and
      electrical properties of Al2O3/ZnO nanolaminates regulated by varying bilayer
      thicknesses. The growth mechanism of nanolaminates based on atomic layer
      deposition and Al penetration into ZnO layer are proposed. The surface roughness
      of Al2O3/ZnO nanolaminates can be controlled due to the smooth effect of
      interposed Al2O3 layers. The thickness, optical constants, and bandgap
      information of nanolaminates have been investigated by spectroscopic ellipsometry
      measurement. The band gap and absorption edge have a blue shift with decreasing
      the bilayer thickness on account of the Burstein-Moss effect, the quantum
      confinement effect and the characteristic evolution of nanolaminates. Also, the
      carrier concentrations and resistivities are found to be modified considerably
      among various bilayer thicknesses. The modulations of these properties are vital
      for Al2O3/ZnO nanolaminates to be used as transparent conductor and high
      resistance layer in optoelectronic applications.

PMID- 29022279
TI  - The role of alpha1- and alpha2-adrenoceptor subtypes in the vasopressor responses
      induced by dihydroergotamine in ritanserin-pretreated pithed rats.
AB  - BACKGROUND: Dihydroergotamine (DHE) is an acute antimigraine agent that displays
      affinity for dopamine D2-like receptors, serotonin 5-HT1/2 receptors and
      alpha1/alpha2-adrenoceptors. Since activation of vascular alpha1/alpha2
      adrenoceptors results in systemic vasopressor responses, the purpose of this
      study was to investigate the specific role of alpha1- and alpha2-adrenoceptors
      mediating DHE-induced vasopressor responses using several antagonists for these
      receptors. METHODS: For this purpose, 135 male Wistar rats were pithed and
      divided into 35 control and 100 pretreated i.v. with ritanserin (100 MUg/kg; to
      exclude the 5-HT2 receptor-mediated systemic vasoconstriction). Then, the
      vasopressor responses to i.v. DHE (1-3100 MUg/kg, given cumulatively) were
      determined after i.v. administration of some alpha1/alpha2-adrenoceptor
      antagonists. RESULTS: In control animals (without ritanserin pretreatment), the
      vasopressor responses to DHE were: (i) unaffected after prazosin (alpha1; 30
      MUg/kg); (ii) slightly, but significantly, blocked after rauwolscine (alpha2; 300
      MUg/kg); and (iii) markedly blocked after prazosin (30 MUg/kg) plus rauwolscine
      (300 MUg/kg). In contrast, after pretreatment with ritanserin, the vasopressor
      responses to DHE were: (i) attenuated after prazosin (alpha1; 10 and 30 MUg/kg)
      or rauwolscine (alpha2; 100 and 300 MUg/kg); (ii) markedly blocked after prazosin
      (30 MUg/kg) plus rauwolscine (300 MUg/kg); (iii) attenuated after 5
      methylurapidil (alpha1A; 30-100 MUg/kg), L-765,314 (alpha1B; 100 MUg/kg), BMY
      7378 (alpha1D; 30-100 MUg/kg), BRL44408 (alpha2A; 100-300 MUg/kg), imiloxan
      (alpha2B; 1000-3000 MUg/kg) or JP-1302 (alpha2C; 1000 MUg/kg); and (iv)
      unaffected after the corresponding vehicles (1 ml/kg). CONCLUSION: These results
      suggest that the DHE-induced vasopressor responses in ritanserin-pretreated
      pithed rats are mediated by alpha1- (probably alpha1A, alpha1B and alpha1D) and
      alpha2- (probably alpha2A, alpha2B and alpha2C) adrenoceptors. These findings
      could shed light on the pharmacological profile of the vascular side effects
      (i.e. systemic vasoconstriction) produced by DHE and may lead to the development
      of more selective antimigraine drugs devoid vascular side effects.

PMID- 29022281
TI  - Isolated Limb Perfusion and Infusion for Extremity Soft Tissue Sarcoma: A
      Contemporary Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Isolated limb perfusion (ILP) and isolated limb infusion (ILI) have
      been variably used in recent years for the treatment of locally advanced or
      marginally resectable extremity soft tissue sarcomas (STSs). We performed a
      systematic review and meta-analysis of contemporary studies to further
      characterize treatment patterns and outcomes. METHODS: PubMed was queried for
      articles published in or after the year 2000, in the English language, with > 10
      patients, and with adequate outcome data following ILP/ILI. Descriptive aggregate
      statistics were performed. RESULTS: Nineteen studies that met the inclusion
      criteria were identified, with a total of 1288 patients. Weighted mean patient
      age was 55.9 years and 52% were male. The majority underwent ILP (88%) versus 12%
      for ILI, and chemotherapeutic regimens used were as follows: (1) melphalan with
      tumor necrosis factor (TNF)-alpha (78%), (2) melphalan +/- actinomycin (10%), and
      (3) other regimens (12%). Most common histologies treated were malignant fibrous
      histiocytoma (21%), liposarcoma (16%), synovial (11%) and leiomyosarcoma (7%).
      Aggregate overall response rate (ORR) post-procedure was 73.3%, with 25.8%
      demonstrating a complete response (CR). Similar unadjusted ORRs were noted in the
      melphalan treatment groups with and without TNFalpha (72.0 and 67.0%,
      respectively; p = 0.27). Grade III toxicity was observed in 15.4% of patients,
      and grade IV/V toxicity was observed in 6.0% of patients. Overall limb salvage
      rate was 73.8% and median time to local (in-field) progression ranged from 4 to
      28 months (weighted median 22.1 months). CONCLUSION: ILP and ILI for extremity
      STS can be safely performed with appreciable response rates and significant limb
      salvage rates. Further study is needed to identify optimal treatment regimens by
      histology.

PMID- 29022282
TI  - Analysis of five cases of human herpesvirus-6 myelitis among 121 cord blood
      transplantations.
AB  - Reports of myelitis associated with human herpesvirus-6 (HHV-6) following
      allogeneic transplantation are rare. Of 121 cases of cord blood transplantation
      (CBT) performed at Nagano Red Cross Hospital, five cases (4.1%) of HHV-6 myelitis
      developed at around the time of engraftment. The major symptom identified in all
      five patients was superficial pain or pruritus linked to segmental levels of the
      spinal cord. Other identified symptoms were fever or low-grade fever in all five
      patients, autonomic nerve disorder in four patients, bladder and rectal
      disturbance in two patients, and extrapyramidal disorder in two patients. These
      symptoms were experienced primarily 16-39 days after CBT. HHV-6 PCR tests were
      all positive for cerebrospinal fluid and for plasma. Of the four cases tested by
      magnetic resonance imaging (MRI), three showed spinal cord abnormality. Antiviral
      therapy using foscarnet or ganciclovir was effective in every case. Although one
      case treated from 12 days after onset experienced long-term pain resembling
      postherpetic neuralgia, symptoms in the four cases were completely relieved after
      antiviral therapy. In summary, the major symptoms of HHV-6 myelitis were
      superficial pain linked to segmental levels of the spinal cord. Prognosis may be
      improved by early initiation of antiviral therapy.

PMID- 29022284
TI  - Correction to: Lipophilic gold(I) complexes with 1,3,4-oxadiazol-2-thione or 1,3
      thiazolidine-2-thione moieties: synthesis and their cytotoxic and antimicrobial
      activities.
AB  - This article has been corrected. One of the author names was given incorrect.
      Please find in this erratum the correct author name: "Heloiza Diniz Nicolella"
      that should be regarded as final by the reader.

PMID- 29022285
TI  - Macular Hole Development After Vitrectomy for Floaters: A Case Report.
AB  - INTRODUCTION: The purpose of this report is to describe a case of macular hole
      development after vitrectomy for floaters with induction of posterior vitreous
      detachment. CASE REPORT: A 44-year-old otherwise healthy man presented with
      visually debilitating floaters in his right eye; these had been present for more
      than 2 years. Preoperative examination was unremarkable in both eyes, apart from
      some degree of vitreous degeneration in the right eye. Preoperative visual acuity
      was 20/20 bilaterally. A 25-gauge transconjunctival sutureless pars plana
      complete vitrectomy with induction of posterior vitreous detachment was performed
      in the right eye. Upon examination 1 month after surgery, a small full-thickness
      macular hole was detected in the right eye. Visual acuity was diminished to
      20/80. The macular hole was closed after a second vitrectomy with internal
      limiting membrane peeling and gas tamponade. CONCLUSION: Macular hole development
      should be listed as a possible complication of vitrectomy for visually
      debilitating floaters when a posterior vitreous detachment is induced during
      surgery.

PMID- 29022283
TI  - Ex Situ Hepatectomy and Liver Autotransplantation for Cholangiocarcinoma.
AB  - BACKGROUND: Hepatic resection of tumors invading the retrohepatic vena cava and
      hepatic veins are a challenge for surgeons, who consider them unresectable most
      of the time.1 , 2 Ex situ hepatectomy and liver autotransplantation has developed
      to improve resectability of these malignancies.3,4 METHODS: The patient was a 51
      year-old man who had jaundice secondary to a intrahepatic cholangiocarcinoma 7 cm
      in diameter in the right lobe of the liver and the caudate lobe. A volumetric
      scan showed a future liver remnant (segments 2 and 3) not sufficient according to
      the body weight. The patient was considered to be unresectable by conventional
      resection due to the critical invasion to the retrohepatic vena cava together
      with the three hepatic veins. Therefore, an ex vivo extended right hepatectomy
      and autotransplantation were indicated. RESULTS: The patient underwent biliary
      decompression through a percutaneous transhepatic catheter and right portal vein
      embolization for left lobe hypertrophy. During the surgery, the liver was removed
      with the retrohepatic vena cava, which was replaced by a prosthetic graft without
      a veno-venous bypass. Ex vivo extended right hepatectomy was performed, and a
      prosthetic graft was used to replace the vena cava where the remaining left
      hepatic vein was anastomosed. The surgery duration was 9 h, and the anhepatic
      time was 4.5 h. The postoperative hospital stay was 19 days, and at this writing,
      3 years later, the patient is disease-free. CONCLUSION: Ex vivo hepatectomy
      without veno-venous bypass should be considered a valid therapeutic option for
      selected patients with cholangiocarcinoma invading the retrohepatic vena cava.

PMID- 29022287
TI  - Correction to: Occurrence and distribution of bovine TB pathology by age, sex,
      and breed of cattle slaughtered in Gusau Abattoir, Zamfara State Nigeria.
AB  - Unfortunately the Abstract was missing in the original version of this article.
      The Abstract is published below. Abstract. This study was aimed to record gross
      lesions suggestive of bovine tuberculosis amongst cattle slaughtered in Gusau
      abattoir Zamfara State, Nigeria.

PMID- 29022286
TI  - Best clinical practice guidance for local analgesia in paediatric dentistry: an
      EAPD policy document.
AB  - BACKGROUND: The European Academy of Paediatric Dentistry (EAPD) proposes this
      best-practice guidance to help practitioners to decide when and how to use local
      analgesia to control pain in children, adolescents, and medically compromised
      individuals during the delivery of oral health care. METHODS: A search of
      different databases was conducted using all terms relevant to the subject.
      Relevant papers were identified after a review of their titles, abstracts or full
      papers. Three workshops were held during the corresponding EAPD interim seminar
      in Torino (Italy) in 2017. Several statements were agreed upon and, furthermore,
      knowledge gaps were identified. RESULTS: An important outcome was that when local
      analgesia administered appropriately-correct choice of agent(s) and dosage,
      proper route of administration-it is, firstly, clinically effective for pain
      control in treating children and, secondly, it carries a very low risk of
      morbidity including adverse or side-effects. Furthermore, several gaps in
      knowledge were identified during the workshop which indicates future research
      needs. Most importantly it remains unsatisfactory that in several European
      countries the most frequently used injectable local analgesic agent, articaine,
      is not approved for usage in children below the age of 4 years. CONCLUSION: When
      considering the dental demand to treat vulnerable (medically compromised)
      children and adolescents in a safe, painless, less-invasive and effective way,
      there seems to be an urgent need to close these gaps in knowledge.

PMID- 29022288
TI  - Comparing the effectiveness of general dietary advice versus a very low energy
      diet in an obese outpatient population in Australia.
AB  - PURPOSE: Obesity is a major public health burden. Outpatient clinics are an
      essential resource for individuals with obesity to access advice for weight loss
      management. The aim of this study was to compare anthropometric and weight loss
      outcomes between participants receiving general dietary (GD) advice, and those on
      a very low energy diet (VLED) under non-trial conditions. METHODS: Data from 276
      adults with obesity attending a multidisciplinary weight management clinic were
      analysed. Changes in anthropometry, body composition, and blood pressure (BP)
      over 12 months were analysed using linear mixed-effects models. RESULTS: Males on
      the GD demonstrated statistically greater reductions in body weight (BW), BMI,
      percent fat mass (FM), systolic BP, waist and hip circumference (p < 0.01).
      Changes in males on a VLED did not reach significance. Females showed
      statistically significant reductions in BW, BMI, waist and hip circumference
      regardless of dietary intervention (p < 0.01); those on the GD significantly
      reduced percent FM (p < 0.001). Females on a VLED had statistically greater
      reductions in BW, BMI and systolic BP compared to those on the GD. No effect of
      exercise physiologist was observed in this study. Participants prescribed a GD
      attended for significantly longer than those on a VLED (p < 0.05), irrespective
      of gender. At 12 months, 14.3 and 4.5% of males and females on a VLED were still
      attending, compared to 10.6 and 4.5% on the GD. CONCLUSIONS: In this
      retrospective study, females in both dietary intervention groups achieved
      significant changes across multiple measures. Only men receiving GD advice
      demonstrated significant changes. LEVEL OF EVIDENCE: Level II-2.

PMID- 29022289
TI  - Cloning of Autophagy-Related MicroRNAs.
AB  - Autophagy is a cellular survival pathway that is necessary for the degradation of
      cellular constituents such as long-lived proteins and damaged organelles.
      Conditions resulting in cellular stress such as starvation or hypoxia might
      activate autophagy. Being at the crossroads of various cellular response
      pathways, dysregulation of autophagy might result in pathological states
      including cancer and neurodegenerative diseases. Autophagy has also been shown to
      participate in stemness. MicroRNAs were introduced as novel regulators of
      autophagy, and accumulating results underlined the fact that they constituted an
      important layer of biological control mechanism on the autophagic
      activity.MicroRNAs are protein noncoding small RNAs that control cellular levels
      of transcripts and proteins through posttrancriptional mechanisms. Novel miRNAs
      in human and mouse genomes are yet to be identified. Considering the emerging
      role of autophagy in health and disease, identification of novel autophagy
      regulating miRNAs and determination of relations between miRNA expression and
      physiological and pathological conditions might contribute to a better
      understanding of mechanisms governing health and disease. High-throughput
      techniques were developed for miRNA profiling, yet for a thorough
      characterization and miRNA target determination, miRNA cloning remains as an
      important step. Here, we describe a modified miRNA cloning method for the
      characterization of novel autophagy-regulating miRNAs.

PMID- 29022290
TI  - Comparison of Safety and Efficacy of Botox and Neuronox in the Management of
      Benign Essential Blepharospasm: A Split-face Study.
AB  - PURPOSE: To compare the efficacy and safety of Botox and Neuronox in the
      management of benign essential blepharospasm (BEB). METHODS: We performed a
      triple-masked, randomized control study to compare Botox and Neuronox in 48 eyes
      of 24 patients with BEB. All 24 patients randomly received Botox or Neuronox in
      the periorbital region in a masked, randomized split-face manner, keeping the
      injection sites and doses uniform. The toxin preparation, injection, and clinical
      evaluations were done by three independent observers. Objective outcome measures
      included improvement in the severity of spasm, grading of the functional visual
      status, changes in palpebral fissure height, lagophthalmos, superficial punctate
      keratitis and Schirmer's test at 2 weeks, 6 weeks, and upon conclusion of the
      effect of the toxin. Subjective outcome measures included duration of the effect
      and a forced choice stating which half of the face was better. Evaluations were
      performed through clinical measurements, external digital photography, and high
      definition videography. RESULTS: The mean duration of relief from spasms was 3.78
      months (standard deviation, 1.58 months; range, 1 to 6 months). The improvement
      in the objective parameters like severity of spasm and functional visual status
      was statistically significant at the 2-week and 6-week follow-up visits (p <
      0.0001). The changes in palpebral fissure height, lagophthalmos, and superficial
      punctate keratitis were equally observed in both groups. At 2 and 6 weeks, three
      of 24 (12.5%) and one of 24 (4%) patients, respectively, reported an unequal
      effect between the two sides of the face, but this difference was not
      statistically significant. At final follow-up (conclusion of the toxin effect),
      patients reported equal effect with no preference for either hemiface. No
      statistically significant differences were found in the comparative analysis
      between the Neuronox and Botox groups. CONCLUSIONS: Neuronox and Botox are
      comparable in terms of their safety and efficacy in the management of BEB.

PMID- 29022291
TI  - Comparison of Contact Lens Corrected Quality of Vision and Life of Keratoconus
      and Myopic Patients.
AB  - PURPOSE: To compare and analyze changes in vision quality, subjective symptoms,
      and psycho-social satisfaction in keratoconus and myopic patients following the
      wearing of contact lenses. METHODS: This study enrolled 25 keratoconus and 25
      myopic patients with corrected vision over 0.8 according to the Snellen chart due
      to treatment with contact lenses. Patients were surveyed prior to the wearing of
      contact lenses, and again after three months of contact lens usage with a
      questionnaire about quality of vision and life. The changes in visual function,
      visual symptoms, and psycho-social well-being before and after contact lens usage
      were analyzed. RESULTS: The keratoconus patients' overall degree of satisfaction
      was higher than the overall degree of satisfaction of myopic patients, and the
      motivation for contact lens usage and purpose of contact lens treatment were
      different in the two groups. Keratoconus patients experienced greater changes in
      satisfaction, particularly in satisfaction during night activities, short
      distance work, and the reading of fine print. Furthermore, they experienced fewer
      dry eye symptoms but greater foreign body sensations than patients with myopia
      following treatment with contact lenses. No statistically significant differences
      in social role functions existed between the two groups. Keratoconus patients had
      a lower expectation of visual acuity recovery before treatment with contact
      lenses (Mann-Whitney U-test, p = 0.049) compared to myopic patients, and more
      anxiety about vision loss following treatment (Wilcoxon signed-rank test, p =
      0.018) compared to their level of anxiety about vision loss before treatment with
      contact lenses. CONCLUSIONS: Although the same treatment was applied, keratoconus
      and myopic patients experienced different types of discomfort and areas of
      improvement in contact lens corrected vision. Therefore, not only corrected
      vision, but also subsequent improvement and discomfort outcomes should be
      considered by patients when choosing contact lens treatment. For patients with
      mild keratoconus, contact lens treatment may be an efficacious first treatment
      modality.

PMID- 29022293
TI  - Correlation between Uncorrected Visual Acuity and Macular Distortion in
      Idiopathic Epiretinal Membrane Patients.
AB  - PURPOSE: To evaluate the association between degree of retinal abnormalities and
      uncorrected visual acuity (UCVA) in idiopathic epiretinal membrane (ERM) patients
      with a small amount of refractive error. METHODS: We retrospectively reviewed 49
      eyes (37 patients) of idiopathic ERM patients. We investigated the association
      between visual acuity and macular status (central macular thickness [CMT], outer
      retinal integrity score, and inner retinal irregularity index) that was assessed
      by optical coherence tomography using multiple linear regression analysis. We
      defined visual acuity difference (VAD) as the difference between UCVA and best
      corrected visual acuity (BCVA). We divided patients into two groups according to
      VAD size and compared clinical characteristics between the two groups. We also
      investigated factors associated with VAD using multiple linear regression
      analysis. RESULTS: BCVA showed significant association with CMT and outer retinal
      integrity score, while UCVA showed significant association with CMT and inner
      retinal irregularity index. Patients with a large VAD showed a similar level of
      BCVA compared to the small VAD group (logarithm of the minimum angle of
      resolution [logMAR], large VAD group 0.11 +/- 0.11 vs. small VAD group 0.13 +/-
      0.12, p = 0.585). However, UCVA was worse (logMAR, large VAD group 0.44 +/- 0.14
      vs. small VAD group 0.18 +/- 0.14, p < 0.001) and inner retinal irregularity was
      higher (large VAD group 1.06 +/- 0.04 vs. small VAD group 1.04 +/- 0.03, p <
      0.001) in patients with a large VAD. On multiple linear regression analysis, the
      absolute value of spherical equivalent (standardized coefficient beta 0.521, p <
      0.001) and inner retinal irregularity index (standardized coefficient beta 0.448,
      p < 0.001) were significantly associated with VAD. CONCLUSIONS: UCVA was
      associated with inner retinal irregularity in idiopathic ERM patients with a mild
      degree of refractive error. Inner retinal irregularity was also associated with
      degree of VAD, suggesting that the effect of refractive error correction is
      greater in patients with more distorted retina.

PMID- 29022292
TI  - Changes in Macular Retinal Layers and Peripapillary Nerve Fiber Layer Thickness
      after 577-nm Pattern Scanning Laser in Patients with Diabetic Retinopathy.
AB  - PURPOSE: The aim of this study was to evaluate the changes in thickness of each
      macular retinal layer, the peripapillary retinal nerve fiber layer (RNFL), and
      central macular thickness (CMT) after 577-nm pattern scanning laser (PASCAL)
      photocoagulation in patients with diabetic retinopathy. METHODS: This
      retrospective study included 33 eyes with diabetic retinopathy that underwent 577
      nm PASCAL photocoagulation. Each retinal layer thickness, peripapillary RNFL
      thickness, and CMT were measured by spectral-domain optical coherence tomography
      before 577-nm PASCAL photocoagulation, as well as at 1, 6, and 12 months after
      577-nm PASCAL photocoagulation. Computerized intraretinal segmentation of optical
      coherence tomography was performed to identify the thickness of each retinal
      layer. RESULTS: The average thickness of the RNFL, ganglion cell layer, inner
      plexiform layer, inner nuclear layer, inner retinal layer, and CMT at each follow
      up increased significantly from baseline (p < 0.001), whereas that of the retinal
      pigment epithelium at each follow-up decreased significantly from baseline (p <
      0.001). The average thickness of the peripapillary RNFL increased significantly
      at one month (p < 0.001). This thickness subsequently recovered to 7.48 MUm, and
      there were no significant changes at six or 12 months compared to baseline (p >
      0.05). CONCLUSIONS: Each macular retinal layer and CMT had a tendency to increase
      for one year after 577-nm PASCAL photocoagulation, whereas the average thickness
      of retinal pigment epithelium decreased at one-year follow-up compared to the
      baseline. Although an increase in peripapillary RNFL thickness was observed one
      month after 577-nm PASCAL photocoagulation, there were no significant changes at
      the one-year follow-up compared to the baseline.

PMID- 29022294
TI  - Epiretinal Membrane: Prevalence and Risk Factors from the Korea National Health
      and Nutrition Examination Survey, 2008 through 2012.
AB  - PURPOSE: To investigate the prevalence and risk factors for an epiretinal
      membrane (ERM) in Korean population. METHODS: Using the database of the Korea
      National Health and Nutrition Examination Survey from 2008 through 2012, 14,772
      participants 40 years of age or older with gradable fundus photographs were
      included. The presence of ERM was determined by using fundus photographs. The
      prevalence of ERM was estimated and possible risk factors including systemic
      factors, nutritional status, and blood tests were analyzed via multiple logistic
      regression analyses. RESULTS: The prevalence of ERM was 2.9% (95% confidence
      interval [CI], 2.6% to 3.3%). On multiple logistic regression analysis, the
      prevalence of ERM was affected by age. The odds ratios (ORs) against the forties
      were 2.70, 5.48, and 5.69 in the fifties, sixties, and seventies, respectively.
      ERM was also significantly affected by cataract surgery (OR, 2.82; 95% CI, 2.08
      to 3.81) and by the increase in intake of 100-mg calcium (OR, 1.05; 95% CI, 1.00
      to 1.11). ERM had negative associations with red blood cell count (OR, 0.66; 95%
      CI, 0.45 to 0.95). CONCLUSIONS: The estimated nation-wide prevalence of ERM in
      Korea is 2.9%. The presence of ERM in the general population is associated with
      age, cataract surgery, increased dietary calcium, and a low red blood cell count.

PMID- 29022295
TI  - Retinopathy of Prematurity-assist: Novel Software for Detecting Plus Disease.
AB  - PURPOSE: To design software with a novel algorithm, which analyzes the tortuosity
      and vascular dilatation in fundal images of retinopathy of prematurity (ROP)
      patients with an acceptable accuracy for detecting plus disease. METHODS: Eighty
      seven well-focused fundal images taken with RetCam were classified to three
      groups of plus, non-plus, and pre-plus by agreement between three ROP experts.
      Automated algorithms in this study were designed based on two methods: the
      curvature measure and distance transform for assessment of tortuosity and
      vascular dilatation, respectively as two major parameters of plus disease
      detection. RESULTS: Thirty-eight plus, 12 pre-plus, and 37 non-plus images, which
      were classified by three experts, were tested by an automated algorithm and
      software evaluated the correct grouping of images in comparison to expert voting
      with three different classifiers, k-nearest neighbor, support vector machine and
      multilayer perceptron network. The plus, pre-plus, and non-plus images were
      analyzed with 72.3%, 83.7%, and 84.4% accuracy, respectively. CONCLUSIONS: The
      new automated algorithm used in this pilot scheme for diagnosis and screening of
      patients with plus ROP has acceptable accuracy. With more improvements, it may
      become particularly useful, especially in centers without a skilled person in the
      ROP field.

PMID- 29022296
TI  - Efficacy and Safety of Intracameral Bevacizumab for Treatment of Neovascular
      Glaucoma.
AB  - PURPOSE: To evaluate the long-term efficacy and safety of intracameral
      bevacizumab in patients with neovascular glaucoma. METHODS: This retrospective
      study included 26 eyes of 26 neovascular glaucoma patients who received
      intracameral bevacizumab injection between January 2013 and May 2015, and were
      followed-up for at least 1 year. All patients were treated with topical and/or
      systemic intraocular pressure (IOP)-lowering medications, intracameral
      bevacizumab, and panretinal photocoagulation (PRP). The main outcome measures
      were changes in visual acuity, IOP, and neovascularization of the iris (NVI) and
      the anterior chamber angle (NVA). To assess the safety of intracameral
      bevacizumab, corneal endothelial changes were also determined using specular
      microscopy. Patients whose IOP was uncontrolled received IOP-lowering surgery.
      Clinical factors associated with IOP-lowering surgery were also investigated.
      RESULTS: In all patients, intracameral bevacizumab resulted in a rapid and marked
      reduction of IOP, NVI, and NVA within 1 week. At 12 months after initial
      injection, 19 of 26 eyes (73%) underwent IOP-lowering surgery. The average
      interval between initial injection and surgical treatment was 33.6 +/- 26.9 days.
      Baseline IOP (p = 0.018), NVA grade (p = 0.029), and incomplete PRP (p = 0.005)
      were identified as predictive factors for IOP-lowering surgery. During the follow
      up period, there were no statistically significant corneal endothelial changes
      after intracameral bevacizumab injection. CONCLUSIONS: During 1 year of follow-up
      after intracameral bevacizumab, the procedure was found to be safe for the
      corneal endothelium. However, the IOP-lowering effect was transient, and 73% of
      patients eventually required IOP-lowering surgery. Predictive factors for IOP
      lowering surgery were high baseline IOP and NVA grade, and incomplete PRP.

PMID- 29022297
TI  - Analysis of the Retinal Nerve Fiber Layer Thickness in Alzheimer Disease and Mild
      Cognitive Impairment.
AB  - PURPOSE: To compare the retinal nerve fiber layer (RNFL) as well as the macula
      volume and thickness in the eyes of age-matched healthy controls with no
      cognitive disabilities with those of elderly people with mild cognitive
      impairment (MCI) or Alzheimer disease (AD). We used optical coherence tomography
      (OCT) to determine the effectiveness of the above quantities for early diagnosis
      of MCI or AD. METHODS: Ninety eyes were considered in this study, split between
      30 normal eyes, 30 eyes from patients with MCI, and 30eyes from patients with AD.
      All subjects underwent ophthalmologic and cognitive examinations, and
      measurements of the RNFL thickness as well as macular volume and thickness were
      taken for all patients using OCT. RESULTS: The mean RNFL thickness upon OCT was
      significantly thinner in the AD group than in the MCI group (p = 0.01). The RNFL
      was thinner in the superior quadrant in patients with AD when compared to the
      healthy controls (p = 0.03). The RNFL thicknesses in the inferior, nasal, and
      temporal quadrants did not differ significantly between the groups. Measurements
      in the 12 clock-hour zones revealed that zone 11 had a significantly thinner RNFL
      in the AD group as compared with the healthy control group (p = 0.02). In zone 2,
      the MCI group had a significantly thinner RNFL than the AD group (p = 0.03).
      CONCLUSIONS: Our OCT findings revealed a neuroanatomic difference in the RNFL
      thickness among the three groups, i.e., the AD, MCI, and healthy control groups.
      This suggests that a change in average RNFL thickness could be a meaningful index
      for diagnosing early AD.

PMID- 29022298
TI  - Patient Awareness of Cataract and Age-related Macular Degeneration among the
      Korean Elderly: A Population-based Study.
AB  - PURPOSE: Age-related eye disease is often considered part of natural aging. Lack
      of awareness of eye conditions can result in missed treatment. We investigated
      the rates of awareness of cataract and age-related macular degeneration, the most
      common age-related eye-diseases, and the associated factors among elderly
      Koreans. METHODS: We identified 7,403 study subjects (>=40 years old) with
      cataract or age-related macular degeneration based on ophthalmic examination
      results during the 5th Korean National Health and Nutrition Examination Survey
      conducted between 2010 and 2012. We assessed whether patients were aware of their
      eye condition based on a previous diagnosis by a physician. RESULTS: The average
      awareness rate over the 3-year study period was 23.69% in subjects with cataract
      and 1.45% in subjects with age-related macular degeneration. Logistic regression
      analysis showed that patients with cataract were more likely to recognize their
      condition if they had myopia (odds ratio, 2.08), hyperopia (odds ratio, 1.33),
      family history of eye disease (odds ratio, 1.44), or a past eye examination (odds
      ratio, 4.07-29.10). The presence of diabetes mellitus was also a significant
      predictor of patient awareness of cataract (odds ratio, 1.88). CONCLUSIONS: Poor
      patient recognition of eye disease among the Korean elderly highlights the
      seriousness of this potential public health problem in our aging society. Pre
      existing eye-related conditions and diabetes were significant predictors of
      awareness; therefore, patients in frequent contact with their doctors have a
      greater chance of detecting eye disease.

PMID- 29022299
TI  - Incidence and Risk Factors of Cystoid Macular Edema after Vitrectomy with
      Silicone Oil Tamponade for Retinal Detachment.
AB  - PURPOSE: To investigate the incidence and risk factors of cystoid macular edema
      (CME) after silicone oil (SO) injection for retinal detachment. METHODS: Fifty
      eight patients with retinal detachment treated by vitrectomy with SO tamponade
      during 2011 to 2015 were retrospectively assigned to CME and non-CME groups.
      Patients underwent complete ophthalmological examination, including color fundus
      photography and preoperative and postoperative optical coherence tomography. Risk
      factors for CME during SO tamponade were determined by regression analyses.
      RESULTS: Of the 58 eyes, 21 (36.2%) exhibited CME. The presence of posterior
      staphyloma in the CME group was significantly more frequent than in the non-CME
      group (p = 0.026). There were no significant differences in other demographic or
      clinical characteristics between the CME and non-CME groups. Significant
      correlations were observed between CME after vitrectomy with SO tamponade and the
      presence of posterior staphyloma (odds ratio, 4.03; p = 0.031). Of the 21 eyes
      with CME, 13 underwent SO removal, among which 11 experienced resolution of CME
      with or without further intervention. CONCLUSIONS: The presence of posterior
      staphyloma is significantly associated with CME after vitrectomy with SO
      tamponade. Patients with retinal detachment exhibiting posterior staphyloma
      should be evaluated for potential CME during SO tamponade.

PMID- 29022300
TI  - Photoacoustic imaging of lymphatic pumping.
AB  - The lymphatic system is responsible for fluid homeostasis and immune cell
      trafficking and has been implicated in several diseases, including obesity,
      diabetes, and cancer metastasis. Despite its importance, the lack of suitable in
      vivo imaging techniques has hampered our understanding of the lymphatic system.
      This is, in part, due to the limited contrast of lymphatic fluids and structures.
      Photoacoustic imaging, in combination with optically absorbing dyes or
      nanoparticles, has great potential for noninvasively visualizing the lymphatic
      vessels deep in tissues. Multispectral photoacoustic imaging is capable of
      separating the components; however, the slow wavelength switching speed of most
      laser systems is inadequate for imaging lymphatic pumping without motion
      artifacts being introduced into the processed images. We investigate two
      approaches for visualizing lymphatic processes in vivo. First, single-wavelength
      differential photoacoustic imaging is used to visualize lymphatic pumping in the
      hindlimb of a mouse in real time. Second, a fast-switching multiwavelength
      photoacoustic imaging system was used to assess the propulsion profile of dyes
      through the lymphatics in real time. These approaches may have profound impacts
      in noninvasively characterizing and investigating the lymphatic system.

PMID- 29022302
TI  - [N-terminomics: proteomic strategies for protein N-terminal profiling].
AB  - Protein N-termini, as the beginning of translation, has a major impact on
      protein's biological functions. Its sequence and various post-translational
      modifications often affect protein activation, stability and cellular
      localization, regulate the signal transduction, and even determine protein's
      final destiny. The systematic study of protein N-termini can clarify the vital
      function of the N-terminus, and provide in-depth knowledge of the multifunctional
      roles that protein has played in diverse biological processes. In addition, N
      terminal research may help us to achieve high-coverage proteomics and re-annotate
      genomics. Combined with our own research, this review highlights recent progress
      of N-terminomics, especially some important enrichment strategies and
      technologies based on mass spectrometry.

PMID- 29022301
TI  - Flexible needle with integrated optical coherence tomography probe for imaging
      during transbronchial tissue aspiration.
AB  - Transbronchial needle aspiration (TBNA) of small lesions or lymph nodes in the
      lung may result in nondiagnostic tissue samples. We demonstrate the integration
      of an optical coherence tomography (OCT) probe into a 19-gauge flexible needle
      for lung tissue aspiration. This probe allows simultaneous visualization and
      aspiration of the tissue. By eliminating the need for insertion and withdrawal of
      a separate imaging probe, this integrated design minimizes the risk of dislodging
      the needle from the lesion prior to aspiration and may facilitate more accurate
      placement of the needle. Results from in situ imaging in a sheep lung show clear
      distinction between solid tissue and two typical constituents of nondiagnostic
      samples (adipose and lung parenchyma). Clinical translation of this OCT-guided
      aspiration needle holds promise for improving the diagnostic yield of TBNA.

PMID- 29022303
TI  - [Progress in omics research of Aspergillus niger].
AB  - Aspergillus niger, as an important industrial fermentation strain, is widely
      applied in the production of organic acids and industrial enzymes. With the
      development of diverse omics technologies, the data of genome, transcriptome,
      proteome and metabolome of A. niger are increasing continuously, which declared
      the coming era of big data for the research in fermentation process of A. niger.
      The data analysis from single omics and the comparison of multi-omics, to the
      integrations of multi-omics based on the genome-scale metabolic network model
      largely extends the intensive and systematic understanding of the efficient
      production mechanism of A. niger. It also provides possibilities for the
      reasonable global optimization of strain performance by genetic modification and
      process regulation. We reviewed and summarized progress in omics research of A.
      niger, and proposed the development direction of omics research on this cell
      factory.

PMID- 29022304
TI  - [Advances in metabolic engineering of Escherichia coli for isoprene
      biosynthesis].
AB  - As an important industrial chemical, isoprene is mainly used as a precursor for
      synthetic rubbers. In addition, it also has wide applications in the field of
      pharmaceutical and chemical intermediates, food, adhesives and aviation fuel.
      Compared with conventional petrochemical routes, production of isoprene in
      microbial systems has been the research focus considering environment friendly
      and sustainable development features. This article summarizes the metabolic
      pathways and key enzymes of isoprene biosynthesis, reviews current methods and
      strategies in improving isoprene production of Escherichia coli, and also gives
      some basic ideas and expectation.

PMID- 29022305
TI  - [Advances and prospects of taxol biosynthesis by endophytic fungi].
AB  - Taxol is one of the most important chemotherapeutic drugs against cancer. Taxol
      has been mainly extracted from the bark of yews for a long time. However, methods
      for the extraction of taxol from the bark of Taxus species were inefficient and
      environmentally costly. As a result of the high ecological toll exacted on trees
      with the potential for Pacific yew extinction, investigators began to look for
      other methods of taxol production. Recently, increasing efforts have been made to
      develop alternative means of taxol production, such as using complete chemical
      synthesis, semi-synthesis, Taxus spp. plant cell culture and microbe
      fermentation. Using microbe fermentation in the production of taxol would be a
      very prospective method for obtaining a large amount of taxol. Therefore, it is
      necessary to understand the molecular basis and genetic regulation mechanisms of
      taxol biosynthesis by endophytic fungi, which may be helpful to construct the
      genetic engineering strain with high taxol output. In this paper, the taxol
      biosynthesis pathway from Taxus cells and the advantages of taxol biosynthesis by
      endophytic fungi were discussed. The study on the isolation and biodiversity of
      taxol-producing endophytic fungi and the taxol biosynthesis related genes are
      also discussed.

PMID- 29022306
TI  - [Preparation and characterization of polyhydroxyalkanoate bioplastics with
      antibacterial activity].
AB  - Polyhydroxyalkanoates (PHAs), as a novel class of biopolymer, are attracting more
      attention due to their diverse material properties and environment-independent
      biodegradability. Here we report the preparation of PHA exhibiting efficient
      antibacterial activity by embedding Nisin, a food additive generally recognized
      as safe, into poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx), a type of
      PHA with high biocompatibility. We first prepared Nisin-containing PHBHHx films
      using solvent casting method. Confocal laser scanning microscopy analysis showed
      that a well-mixed integrated structure of the films with an even distribution of
      the Nisin particles in the PHBHHx matrices. Then the antimicrobial activity of
      PHBHHx/Nisin films against Micrococcus luteus was quantified on agar plate by
      measuring the size of inhibition zone. Cultivation in liquid media further
      confirmed the releasing of Nisin from the films and the long-time antibacterial
      activity. Results showed that the threshold of Nisin concentration for long-time
      and effective inhibition against bacteria growth is 25 MUg/g. These results
      altogether establish a technological foundation for the application of PHA in
      biomedicine and food industry.

PMID- 29022307
TI  - [Expression, purification and characterization of arabinose-5-phosphate isomerase
      from Arabidopsis thaliana].
AB  - Arabinose-5-phosphate isomerase (KdsD) is the first key limiting enzyme in the
      biosynthesis of 3-deoxy-D-manno-octulosonate (KDO). KdsD gene was cloned into
      prokaryotic expression vector pET-HTT by seamless DNA cloning method and the
      amount of soluble recombinant protein was expressed in a soluble form in E. coli
      BL21 (DE3) after induction of Isopropyl beta-D-1-thiogalactopyranoside (IPTG).
      The target protein was separated and purified by Ni-NTA affinity chromatography
      and size exclusion chromatography, and its purity was more than 85%. Size
      exclusion chromatography showed that KdsD protein existed in three forms:
      polymers, dimmers, and monomers in water solution, different from microbial KdsD
      enzyme with the four polymers in water solution. Further, the purified protein
      was identified through Western blotting and MALDI-TOF MASS technology. The
      results of activity assay showed that the optimum pH and temperature of AtKdsD
      isomerase activities were 8.0 and 37 C, respectively. The enzyme was activated by
      metal protease inhibitor EDTA (5 mmol/L) and inhibited by some metal ions at
      lower concentration, especially with Co2+ and Cd2+ metal ion. Furthermore, when D
      arabinose-5-phosphate (A5P) was used as substrate, Km and Vmax of AtKdsD values
      were 0.16 mmol/L, 0.18 mmol/L.min. The affinity of AtKdsD was higher than KdsD in
      E. coli combined with substrate. Above results have laid a foundation for the
      KdsD protein structure and function for its potential industrial application.

PMID- 29022308
TI  - [Expression and production optimization of sucrose isomerase from Pantoea
      dispersa in Escherichia coli].
AB  - To improve the yield of sucrose isomerase from Pantoea dispersa UQ68J, we studied
      the effect of different signal peptides and fermentation conditions on sucrose
      isomerase expression in Escherichia coli. The gene of sucrose isomerase was
      optimized and expressed in E. coli BL21 (DE3) with native signal peptide which
      was named as ORI strain. The total and extracellular enzyme activity was 85 and
      65 U/mL in the flask, respectively. The mature protein, which started from the
      22th amino acid, was connected with the PelB and OmpA signal peptide to construct
      P22 and O22 strain, respectively. The total activity of P22 reached 138 U/mL,
      which was 1.6 times of ORI strain. The total activity of O22 strain was similar
      to that of ORI strain. Induced by 3.0 g/L lactose, the total activity of P22
      strain increased to 168 U/mL. In 3 L fermentor, the effects of glycine
      concentration and induction time were studied. Induction when the DCW reached 18
      g/L (OD600=30), with 0.5% glycine, the extracellular enzyme activity reached 1
      981 U/mL, and the total enzyme activity reached 2 640 U/mL, which is the highest
      activity of sucrose isomerase that was expressed in recombinant E. coli.

PMID- 29022309
TI  - [Construction of an Escherichia coli strain for sensitive detection of arsenite
      ion in water].
AB  - In order to construct an Escherichia coli strain with high sensitivity and
      specificity to detect arsenic ion using fluorescence as reporter, a sensitive
      strain to arsenic ion was obtained by knocking out the gene arsB that acts as an
      arsenic efflux pump. The pET28b vector containing arsenite detecting cassette
      Pars-arsR-egfp was constructed and then transformed into arsB deleted mutant.
      Measuring conditions of this constructed whole-cell biosensor were optimized and
      its linear concentration range, limit of detection and specificity were
      determined. This modified biosensor was much more sensitive than that using wild
      type strain as host. The optimal detection range of As3+ concentration was 0.013
      to 42.71 MUmol/L, and the limit concentration of detection was as low as 5.13
      nmol/L. Thus we successfully improved the sensitivity of arsenite detecting
      biosensor by modification of E. coli genome, which may provide useful strategies
      for development and optimization of microbial sensors to detect heavy metals.

PMID- 29022310
TI  - [In vitro observation of haemolymph melanization and melanin-related biosynthesis
      enzyme genes in silkworm, Bombyx mori].
AB  - The observation statistics suggested that the haemolymph melanization speed of
      larvae became fast and the growth inhibition of Escherichia coli was strong as
      the quantities of feeding on mulberry leaves increased. The RT-PCR result showed
      that the mRNA expressions of melanin biosynthesis enzyme BmTan, BmPo-1, BmYellow
      f and BmDdc were high in the haemolyph of 5 L 3 d larvae. The qPCR analysis
      showed Bmtan, Bmddc, Bmyellow, Bmebony and Bmblack, especially Bmddc expression
      were significantly higher in black disease larvae than in normal larvae. Compared
      with control, Ddc inhibitors drastically inhibited the lipopolysaccharide-induced
      haemolymph melanization. In addition, the content of Dopa and Dopamine markedly
      rose after E. coli injection. These indicated that haemolymph melanization was
      linked to immune defenses and Bmddc may play a role in melanization response of
      haemolymph immune in silkworm.

PMID- 29022311
TI  - [Hyaluronic acid production by Streptococcus iniae and its application in rabbit
      skin's regeneration].
AB  - Hyaluronic acid (HA) is an important biomaterial as the extracellular matrix in
      human body. We produced HA by fermentation of Streptococcus iniae (Strep.).
      Production of HA by Strep. was evaluated and further improved by strain mutation
      by ultraviolet. One strain with higher HA yield and lower content of protein was
      obtained. Its HA yield increased from (82.3+/-3.3) mg/L to (120+/-10.6) mg/L, and
      protein decreased from (0.178+/-0.011) mg/L to (0.032+/-0.017) mg/L. The
      molecular weight (MW) of HA yield from Strep. is about 3.0*105 Da. Using the
      method of freezing and thawing, HA aqueous solution was transferred into
      hydrogel. This HA hydrogel, casted on sterilized non-woven fabric, was applied to
      repair rabbit skin with full-thickness defect. The preliminary results of the
      animal tests displayed that HA hydrogel obviously reduced the inflammation around
      the wound and promoted the skin regeneration comparing with the control tests.

PMID- 29022312
TI  - [Influence of PCR cycle number on microbial diversity analysis through next
      generation sequencing].
AB  - Using of high throughput sequencing technology to study the microbial diversity
      in complex samples has become one of the hottest issues in the field of microbial
      diversity research. In this study, the soil and sheep rumen chyme samples were
      used to extract DNA, respectively. Then the 25 ng total DNA was used to amplify
      the 16S rRNA V3 region with 20, 25, 30 PCR cycles, and the final sequencing
      library was constructed by mixing equal amounts of purified PCR products.
      Finally, the operational taxonomic unit (OUT) amount, rarefaction curve,
      microbial number and species were compared through data analysis. It was found
      that at the same amount of DNA template, the proportion of the community
      composition was not the best with more numbers of PCR cycle, although the species
      number was much more. In all, when the PCR cycle number is 25, the number of
      species and proportion of the community composition were the most optimal both in
      soil or chyme samples.

PMID- 29022313
TI  - [Prokaryotic expression and purification of Chlamydomonas reinhardtii
      intraflagellar transport protein 46(IFT46) and preparation of polyclonal
      antibody].
AB  - IFT46 is one of the important components of intraflagellar transport complex B in
      Chlamydomonas reinhardtii, and plays important roles in the assembly, movement
      and perception of ciliary. To study its functional mechanism, a GST-tagged and an
      MBP-tagged prokaryotic expression plasmid, pGEX-2T-ift46 and pMAL-C2X-ift46 were
      constructed, respectively, by inserting ift46 into the pGEX-2T and pMAL-C2X
      vector, and then transformed into Escherichia coli BL21 (DE3) for protein
      expression. SDS-PAGE (15%) analysis results showed that the molecular weights of
      the fusion protein GST-IFT46 and MBP-IFT46 were 70 kDa and 86 kDa, respectively.
      We used the fusion protein GST-IFT46 purified by affinity adsorption purification
      (more than 95% purity) for immunity to New Zealand white rabbits. The 5th immune
      serum was collected and the antibody titer was determined to be 256 000 by ELISA.
      The antiserum was purified by Protein A affinity adsorption purification and
      immobilized MBP-IFT46 purification, and the specificity of polyclonal antibodies
      was evaluated by Western blotting and immunofluorescence. Results showed that the
      polyclonal antibody prepared could specifically and precisely bind IFT46 in C.
      reinhardtii, and IFT46 was mainly concentrated at basal body regions and few
      localized along the entire length of the flagellum as punctuated dots, which will
      make a foundation to further study the mechanism of IFT46 in cilia related
      diseases such as obesity, diabetes and polycystic kidney disease.

PMID- 29022314
TI  - [Expression of the reporter LacZ driven by human dentin sialophosphoprotein
      promoter in human dental mesenchymal cells].
AB  - The expression of dentin sialophosphoprotein (DSPP) is the marker for cells
      differentiated into odontoblasts. This study attempted to analyze the DSPP
      promoter and build the reporter LacZ expression system driven by this promoter,
      which allows convenient and quick detection of odontoblast cells. First, we
      separated the human dental mesenchymal cells in which the expression of DSPP can
      be effectively induced by dexamethasone. Second, four 5' flanking regions of
      human DSPP gene (- 4 000-+54, -2 500-+54, -1 447-+54 and -1 027-+54) were
      analyzed, the results showed that the highest promoter activity lied in the -2
      500-+54 region. The promoter activity is reduced when the 5' flanking region was
      extended from -2 500 to -4 000 bp upstream from the transcription start site; The
      promoter activity are also decreased when the 5' flanking regions were shorted
      from -2 500 to -1 447 bp and from -1 447 to -1 027 bp, indicating that potential
      suppresser elements are lied in the region between -4 000 and -2 500 bp and
      potential activator elements are lied in the region between -2 500 and -1 027 bp.
      Then we constructed the lentiviral report vector phDSPP-LacZ containing the -2
      500-+ 54 promoter region in front of the LacZ gene. The expression of LacZ was
      detected using X-Gal staining in both human dental mesenchymal cells and
      immortalized human dental mesenchymal cells infected with phDSPP-LacZ. The phDSPP
      LacZ lentiviral vector may provide a more convenient method to detect the
      expression of DSPP in human odontogenic differentiation, tooth development and
      tooth regeneration studies.

PMID- 29022315
TI  - [Mutagenesis of Methylobacterium extorquens AM1 for increasing pyrroloquinoline
      quinone production by atmospheric and room temperature plasma].
AB  - As a novel cofactor of oxidoreductase, pyrroloquinoline quinone (PQQ) has a great
      potential of application in medicine, food industries. In order to improve the
      efficiency of the PQQ production by Methylobacterium extorquens AM1, the strain
      was treated by atmospheric and room temperature plasma (ARTP). Positive mutants
      with changes in PQQ yield were obtained based on a high-throughput screening
      approach. After ARTP treatment, analysis data show that the positive mutation
      rate was 31.6%. Furthermore, we obtained an excellent positive mutant M.
      extorquens AM1 (E-F3) with the yield of 54.0 mg/L PQQ, which was approximately 3
      times as much compared with that of the wild-type strain. The robust high
      throughput screening method for mutagenesis by ARTP improves PQQ production. In
      addition, this method also provides a new strategy for further strain
      improvement.

PMID- 29022316
TI  - [Advances in biosynthesis of 2-phenylethanol by yeasts].
AB  - 2-Phenylethanol (2-PE) is an aromatic alcohol with a pleasant rose-like
      fragrance. It has been widely used in food, cosmetic, and pharmaceutical
      industry. Most of 2-PE is produced by chemical synthesis, but the use of
      chemically synthesized product is restricted in some fields. 2-PE from plant
      extraction is natural but its production is very low. Microbial biotransformation
      is a promising process to produce natural 2-PE. In this paper, we review recent
      research progress in the synthetic metabolic pathways and regulatory processes of
      2-PE in yeast, and strategies for improving 2-PE production. Moreover, we discuss
      the limitation of current progress and future research directions.

PMID- 29022318
TI  - [Application of inteins in building protein affinity purification system].
AB  - Intein is a part of polypeptide in the premature protein with the capability of
      self-splicing, which is widely applied in protein purification, protein
      conjuction, cyclopeptide preparation, protein labeling and biosensor. In this
      review, we summarized the development of intein used in protein purification,
      discussed intein-mediated chromatographic and non-chromatographic purification
      systems, and summarized the researches in manipulating intein cleavage reaction.
      This work is to provide clues for improvement of intein-mediated protein
      purification.

PMID- 29022317
TI  - [Application of next generation sequencing in studying food microorganisms-a
      review].
AB  - Next generation sequencing technology has revolutionized studies in fermentation
      process, in particular, to explore the mechanism by which food microorganisms,
      including physiology, metabolic pathways, diversity and dynamic changes of
      microbial community. In addition, phylogenetic characteristics of different
      species or strains of the food microorganisms are disclosed. All these aspects
      will help explain how the microbes are interacting and responding to
      environmental factors. Bioinformatics analysis of genome and metagenome sequence
      data of food microorganisms could provide essential clues to improve fermentation
      process and function of microbes as well as control and prevention of foodborne
      disease outbreak. In this review, we summarized recent genomics and metagenomics
      studies on food microorganisms. The impact of next generation sequencing for the
      development and trends of food microorganism researches were discussed in
      details.

PMID- 29022319
TI  - [Progress of autophagy in regulating liver homeostasis].
AB  - Liver is the largest human digestive gland and the most important metabolic
      organ. When autophagy was proposed during studying liver lysosomes in the 1960s,
      it was found that nutrient levels and hormones could influence autophagy
      activity. Recent studies show that autophagy is not only normal physiological
      processes, but also involved in the regulation of many pathological processes.
      This article summarizes the role of liver autophagy in the maintenance of
      homeostasis in the healthy liver, and provides new ideas for liver physiology and
      treating diseases associated with autophagy disorders.

PMID- 29022320
TI  - [Protein expression profile of mast cells in response to recombinant VP1-VP4 of
      foot-and-mouth disease virus].
AB  - To reveal the innate immunity of mast cells against recombinant VP1-VP4 protein
      of foot-and-mouth disease virus (FMDV), mouse peritoneal mast cells (PMCs) were
      pulsed with recombinant VP1-VP4 protein. The supernatants harvested from PMCs
      cultures were applied to the high throughput ELISA array. Our results show that
      the expression levels of CCL19, L-selectin, CCL17, and TNF alpha released from
      PMCs pulsed with recombinant VP1-VP4 were significantly down-regulated compared
      with PMCs alone (P<0.001). Surprisingly, in comparison with PMCs alone, the
      expression levels of CCL19, IL-15, IL-9, G-CSF, and Galectin-1 in PMCs with the
      mannose receptor (MR) inhibitor were significantly up-regulated (Plt;0.01), and
      the expression level of IL-10 was also remarkably up-regulated (Plt;0.05).
      Importantly, the protein expression levels in PMCs treated with MR inhibitor were
      higher than PMCs pulsed with VP1-VP4, including IL-10, IL-17, CCL20, IL-15, IL-9,
      L-selectin, CCL17, TNF alpha, and CCL19 (Plt;0.01) as well as CCL21, and G-CSF
      (Plt;0.05). Differential expression analysis in bioinformatics shows that both L
      selectin and CCL17 were recognized as differentially expressed protein molecules
      (Log2(ratio)<=-1) when compared with PMCs alone. Furthermore, the up-regulation
      of the expression levels of CCL20, CCL19, L-selectin, and IL-15 in PMCs treated
      with MR inhibitor was defined as differential expression (Log2(ratio)>=1). These
      data indicate that PMCs are capable of secreting CCL19, L-selectin, CCL17, and
      TNF alpha spontaneously and the recombinant VP1-VP4 has an inhibitive potential
      to PMCs during their performance of innate immune response. Given the protein
      expression levels from PMCs pre-treated with MR inhibitor were significantly
      increased, it can be deduced that immunosuppression of FMDV is presumably
      initiated by the VP1 recognition of MR on mast cells.

PMID- 29022321
TI  - [PKB/Akt regulates the aggregation of actin by Girdin in mouse fertilized eggs].
AB  - The purpose of this study is to reveal the role of Girdin in regulating the
      aggregation of actin filaments by studying the relationship between PKB/Akt and
      Girdin. First we used Scansite software (http://scansite.mit.edu) to predict
      relevant target sites of PKB/Akt on mouse Girdin. To gain insight into the role
      of phosphorylation of Girdin by PKB/Akt, we assessed the location of
      phosphorylated Girdin in fertilized eggs by staining with anti-P-Girdin 1 417 Ab.
      We detected a distinct increase in the fluorescence signal of F-actin and P
      Girdin 1 417 after microinjection of Akt WT and myr-Akt. The addition of myr-Akt
      induced phosphorylation of Girdin in mouse fertilized eggs. In addition, siRNA
      mediated Akt-knockdown blocked phosphorylation of Girdin. The distribution of
      actin filaments was obviously scattered. These results strongly suggest that
      PKB/Akt could directly phosphorylate Girdin on Ser1 417 and promote its function
      in mouse fertilized eggs.

PMID- 29022322
TI  - [Construction and optimization of microbial cell factories for producing cis, cis
      muconic acid].
AB  - cis, cis-muconic acid (MA) is an important platform chemical. Now, majority of
      reported engineered strains are genetically instable, the exogenous genes are
      expressed under the control of expensive inducer and the components of their
      fermentation medium are complex, thus large-scale microbial production of MA is
      limited due to the lack of suitable strains. Hence, it is still necessary to
      construct novel high-performance strain that is genetically stable, no induction
      and grows in simple inorganic fermentation medium. In this study, after 3
      exogenous genes (aroZ, aroY, catA) for biosynthesis of MA were integrated into
      previously constructed 3-hydroshikimate producing Escherichia coli WJ060 strain
      and combinatorially regulated with 3 constitutive promoters with different
      strengths, 27 engineered strains were constructed. The best engineered strain, E.
      coli MA30 could produce 1.7 g/L MA in the simple inorganic fermentation medium
      without induction. To further enhance the production capacity of MA, the mutant
      library of E. coli MA30 was constructed by genome replication engineering and
      screened via high-throughput assay. After two-round screening, the new strain, E.
      coli MA30-G2 with improved production of MA was obtained, and the titer of MA
      increased more than 8%. Under the condition of 5 L fed-batch fermentation, E.
      coli MA30-G2 could produce about 11.5 g/L MA. Combinatorial regulation and high
      throughput screening provide important reference to microbial production of other
      bio-based chemicals.

PMID- 29022324
TI  - [Stability enhancement of urethanase from Lysinibacillus fusiformis by site
      directed mutagenesis].
AB  - Ethyl carbamate as a potential carcinogen commonly exists in traditional
      fermented foods and beverages. Enzymatic removal of ethyl carbamate from
      fermented foods and beverages is an efficient and safe method. In this study, we
      mutated urethanase from Lysinibacillus fusiformis SC02 on the Q328 site through
      computer aided design approaches. The half-life of resulting mutants Q328C and
      Q328V was detected to be 7.46 and 1.96 folds higher than that of the original
      enzyme, and Q328R presented better thermal-tolerance than the original urethanase
      when incubated at high temperature. The tolerance of Q328C to ethanol and acid
      also increased when compared with that of the original enzyme. The stability and
      tolerance to acid and ethanol of urethanase could be improved by modification on
      its Q328 site.

PMID- 29022323
TI  - [Fitness analysis between the L-sorbosone dehydrogenase modules and
      Ketogulonigenium vulgare chassis].
AB  - Ketogulonigenium vulgare is an acid-producing strain in the process of two-step
      vitamin C fermentation. L-sorbosone dehydrogenase (SNDH) is one of the key
      enzymes during the biosynthesis of 2-keto-L-gulonic acid (2-KGA), the precursor
      of vitamin C. However, the catalytic mechanism of SNDH is unclear. According to
      the whole genome sequencing of K. vulgare, two genes encoding sorbosone
      dehydrogenases, one derived from the chromosome (named as sndhg) and one from
      plasmid (named as sndhp), were introduced into an industrial strain K. vulgare.
      The overexpression of gene sndhg had hardly effect on 2-KGA production, and the
      overexpression of gene sndhp produced an obvious byproduct in the fermentation
      broth. Combinational expression of sndhg/sndhp with pqqA (obtaining sndhg-pqqA
      and sndhp-pqqA modules) in K. vulgare resulted in the similar fermentation
      phenotype to two previous strains. After serial sub-cultivation of co-cultured
      Bacillus endophyticus with each engineered K. vulgare for 50 d, the conversion
      rate of 2-KGA increased by 15.4%, 179%, 0.65% and 125% compared with that of the
      parental K. vulgare with B. endophyticus. This study shows that adaptive
      evolution of microbial consortium is an effective strategy to increase the
      fitness between functional modules and chassis, thus quickly getting better
      strains for production of 2-KGA.

PMID- 29022325
TI  - [Thermal stability improvement for phenylalanine hydroxylase by site-directed
      mutagenesis].
AB  - In proteins of thermophilic bacteria, Gly is tend to be replaced by Ala and Lys
      is tend to be replaced by Arg to adapt the high temperature. In order to improve
      the thermal stability of phenylalanine hydroxylase (PAH) from Chromobacterium
      violaceum, all the Gly on PAH were mutated to Ala and Lys to Arg. Positive mutant
      enzymes with improved thermal stability were selected, followed by combined
      mutation and characterization. The results revealed that half-lives of K94R and
      G221A mutants at 50  degrees C were 26.2 min and 16.8 min, which were increased
      by 1.9-times and 0.9-times than the parent enzyme (9.0 min). The residual
      activity of K94R/G221A mutant was improved to 65.6% after keeping at 50  degrees
      C for 1 h, which was 6.6 time higher than the parent enzyme (8.6%). Circular
      dichroism (CD) spectroscopy revealed that Tm values of the parent enzyme, K94R,
      G221A and K94R/G221A were 51.5 C, 53.8 C, 53.1 C and 54.8 C, respectively.
      According to the protein structure simulation, the two mutations were located on
      flexible loop. In the K94R mutant, the mutated Arg94 on the surface of the enzyme
      formed an extra hydrogen bond with Ile95, which stabilized the located loop. In
      the G221A mutant, the mutated Ala221 formed hydrophobic interaction with Leu281,
      which could stabilize both the loop and flexible area of the C-terminus of G221A.
      The results not only provided a reference for protein modification on thermal
      stability, but also laid the foundation for application of phenylalanine
      hydroxylase in the field of functional foods.

PMID- 29022326
TI  - [Integration and expression of Xa21 in transgenic rice CX8621].
AB  - Agrobacterium tumefaciens-mediated transformation system has been widely applied.
      However, the function of target gene is affected by multiple factors. With this
      system, we obtained a transgenic rice line CX8621 carrying the bacterial blight
      resistance gene Xa21. In previous work, we have confirmed that it was selectable
      maker-free and vector backbone-free. And after 16 generations of breeding, it
      still maintained perfect resistance to bacterial blight disease. On this basis,
      we analyzed the integration and expression of Xa21 in CX8621 at the present
      study. First, based on the border sequences of plasmid pBXa21 and Xa21, we
      designed nested primers and assured the integrity of Xa21 in CX8621. Second, we
      cloned the flanking sequences and located Xa21 on chromosome 2 using improved
      Tail-PCR. Then we analyzed the expression pattern of Xa21 in several tissues and
      at different developmental stages by RT-PCR. The results show that Xa21 can be
      stably expressed in CX8621, agreeing well with the disease resistance response as
      reported previously. In addition, we detected the protein levels of XA21 in
      CX8621 with antibody of natural XA21 protein. Surprisingly, no XA21 protein was
      detected in the seeds of CX8621. Thus, the integration and expression analysis of
      Xa21 in CX8621 provided a part of scientific evidences for the safety assessment
      of genetically modified rice.

PMID- 29022327
TI  - [Comparison of MITE transposons mPing in different rice subspecies].
AB  - The mPing family is the first active MITE TE family identified in rice genome. In
      order to compare the compositions and distributions of mPing family in the
      genomes of two rice subspecies japonica (cv. Nipponbare) and indica (cv. 93-11),
      we initially estimated the copy numbers of mPing family in those two subspecies
      using Southern blot and then confirmed the results by searching homologous copies
      in each reference genome using Blastn program, which turned out to have 52 and 14
      mPing copies in corresponding reference genome, respectively. All mPing members
      in Nipponbare genome belong to mPing-1, while there are 3 mPing-1 and 11 mPing-2
      copies in 93-11 genome. By further investigating the 5-kb flanking sequences of
      those mPing copies, it was found that 23 and 3 protein-coding genes in Nipponbare
      and 93-11 genome are residing adjacent to those mPing copies respectively. These
      results establish the preliminary theoretical foundation for further dissecting
      the genetic differences of japonica and indica rice in terms of the diversities
      and distributions of their component mPing.

PMID- 29022328
TI  - [Prokaryotic expression, purification and identification of recombinant human
      atrial natriuretic peptide].
AB  - In order to improve the expression of recombinant human atrial natriuretic
      peptide (ANP), a new plasmid (pET28a(+)/ANP3) containing 3 tandem ANP genes with
      lysine codon as the interval linker, was constructed. Target gene was transformed
      into Escherichia coli BL21 (DE3) and induced by IPTG, about 60% of the total-cell
      protein was the target protein, His6-ANP3. After denaturation and refolding, it
      was digested by Endoproteinase Lys-C and Carboxypeptidase B (CPB) and then
      purified by a series of purification processes, about 16 mg purified ANP monomer
      could be obtained from one liter bacteria broth of shaking culture. Ultimately,
      the purity of protein was above 90% determined by UPLC and Tricine SDS-PAGE, its
      molecular weight was 3 080 Da according to LC-MS identification and it was proved
      to be equivalent to the reference product by ELISA. The use of tandem gene
      expression can provide a new possible model for the expression of other peptide
      drugs.

PMID- 29022329
TI  - [Effects of light quality on cell growth and psbA promoter of engineered
      Synechococcus sp. PCC7002].
AB  - Light quality can regulate both psbA genes and vector promoter psbA of the
      engineered Synechococcus. Through light regulation, we tried to improve yield of
      the recombinant protein for vp28 gene-expressed Synechococcus sp. PCC7002. To
      drive photon-capturing efficiently, three limiting factors (irradiance,
      temperature and pH) were optimized by measuring net photosynthesis. High cell
      density cultures were performed with variant ratios of white, red and blue light
      in a 5-L photo-bioreactor. Yields of biomass, expressions of vp28 and
      transcription levels of psbA were compared. High ratio blue light-induced vp28
      transcription had tripled and the relative accumulation of VP28 protein was
      doubled. The relative expressions of psbAII and psbAIII had positive correlations
      with higher ratio of blue light, not the red light. With high ratio red light
      inducing, dry biomass reached 1.5 g/L in three days. Therefore, we speculated
      that red light accelerated biomass accumulation of the transgenic strain and blue
      light promoted transcription for PpsbA and psbA. These results provided useful
      information for mass production of cyanobacteria and its secondary metabolites.

PMID- 29022330
TI  - Bladder stone management: an update.
AB  - INTRODUCTION: Bladder stone (BS) is a rare disease curable with several options.
      Herein, we reviewed the specific literature in order to update the current BS
      management. EVIDENCE ACQUISITION: A comprehensive systematic MEDLINE search was
      performed for English language reports published before April 2017 using the BS
      related terms, i.e. bladder-vesical calculi, lithotripsy. Then manuscripts
      references were screened to identify unfounded studies. Studies regarding BS in
      children were excluded. EVIDENCE SYNTHESIS: Retrieved studies were classified
      according to their main item as: etiology, diagnosis, treatment, treatment in
      specific illnesses and advances in BS management. Treatment option was mainly
      related to stone size and number as well as concomitant causative disease.
      However, stone nature was not analyzed in all the retrieved studies. Both trans
      urethral and percutaneous lithotripsy were efficacy for stone fragmentation
      although the last one was suggested to avoid urethral injuries. Holmiun:Yag laser
      lithotripsy has made stone fragmentation feasible by using local anesthesia
      however in selected patients only. The urological dogma to perform concomitant
      prostate surgery in men with BS has been recently questioned by some
      observational case-series studies however, the lack of randomization and long
      follow up preserve that knowledge. CONCLUSIONS: Bladder stone is a rare and
      ancient disease. Nowadays new technologies have been developed in the effort to
      make less invasive stone treatment. The retrieved studies show that stone
      fragmentation can be archived by using several surgical approaches and devices
      whereas comparative randomized studies are still unavailable to identify the best
      option.

PMID- 29022331
TI  - Trial of Tocilizumab in Giant-Cell Arteritis.

PMID- 29022332
TI  - Trial of Tocilizumab in Giant-Cell Arteritis.

PMID- 29022333
TI  - Health Effects of Overweight and Obesity in 195 Countries.

PMID- 29022334
TI  - Health Effects of Overweight and Obesity in 195 Countries.

PMID- 29022335
TI  - Paper/Carbon Nanotube-Based Wearable Pressure Sensor for Physiological Signal
      Acquisition and Soft Robotic Skin.
AB  - A wearable and flexible pressure sensor is essential to the realization of
      personalized medicine through continuously monitoring an individual's state of
      health and also the development of a highly intelligent robot. A flexible,
      wearable pressure sensor is fabricated based on novel single-wall carbon nanotube
      /tissue paper through a low-cost and scalable approach. The flexible, wearable
      sensor showed superior performance with concurrence of several merits, including
      high sensitivity for a broad pressure range and an ultralow energy consumption
      level of 10-6 W. Benefited from the excellent performance and the ultraconformal
      contact of the sensor with an uneven surface, vital human physiological signals
      (such as radial arterial pulse and muscle activity at various positions) can be
      monitored in real time and in situ. In addition, the pressure sensors could also
      be integrated onto robots as the artificial skin that could sense the
      force/pressure and also the distribution of force/pressure on the artificial
      skin.

PMID- 29022336
TI  - Methylsiloxanes Release from One Landfill through Yearly Cycle and Their Removal
      Mechanisms (Especially Hydroxylation) In Leachates.
AB  - In one yearly cycle (2016), D4 and D5 were detected in biogas samples (n = 36,
      0.105-2.33 mg/m3) from a Chinese municipal landfill, while D4-D6 were detected in
      influents/effluents of leachate storage pond (n = 72, < LOQ-30.5 MUg/L). Mass
      loads of cVMS in both biogas (591-6575 mg/d) and leachate influents (659-5760
      mg/d) increased from January to July (summer), and then decreased from July to
      December (winter). Removal experiments indicated that 1) hydrolysis and
      volatilization were predominant removal mechanism for D4 and D5, respectively, in
      leachate storage pond, responsible for their more significant removal (94.5-100%)
      in August; 2) indirect phototransformation (t1/2 = 25.5-87.0 days), such as
      hydroxylation by OH radical generated in leachates, was the predominant (50.0
      75.5%) removal pathway for D6, which led to the largest removal efficiencies
      (65.2-73.7%) in June, the month with the largest sun light intensity and highest
      photosensitizer (e.g., Fe2+ and NO3-) concentrations. Monohydroxylated products
      of D5 and D6, D4TOH and D5TOH, were detected in leachate effluents (39.6-187
      ng/L) during May-July. Compared to D5 and D6, volatilization half-lives of D4TOH
      (86.3 days) and D5TOH (177 days) in leachates were 2.9 and 1.4 times longer,
      while their hydrolysis half-lives (7.50 days for D4TOH and 21.5 days for D5TOH)
      were 7.1 and 10 times shorter, respectively.

PMID- 29022337
TI  - Asymmetric Syntheses of 3-Deoxy-3-aminosphingoid Bases: Approaches Based on
      Parallel Kinetic Resolution and Double Asymmetric Induction.
AB  - The asymmetric syntheses of a range of N- and O-protected 3-deoxy-3
      aminosphingoid bases have been achieved using two complementary approaches. dl
      Serine was converted to a racemic N,N-dibenzyl-protected gamma-amino-alpha,beta
      unsaturated ester which was resolved using a parallel kinetic resolution (PKR)
      strategy upon reaction with a pseudoenantiomeric mixture of lithium (R)-N-benzyl
      N-(alpha-methylbenzyl)amide and lithium (S)-N-3,4-dimethoxybenzyl-N-(alpha
      methylbenzyl)amide, giving the corresponding enantio- and diastereoisomerically
      pure beta,gamma-diamino esters. Alternatively, elaboration of l-serine gave the
      corresponding enantiopure N,N-dibenzyl-protected gamma-amino-alpha,beta
      unsaturated ester, and doubly diastereoselective conjugate addition of the
      antipodes of lithium N-benzyl-N-(alpha-methylbenzyl)amide was found to proceed
      under the dominant stereocontrol of the lithium amide reagent in both cases, thus
      augmenting the accessible range of beta,gamma-diamino esters. Both of these
      protocols were expanded to include in situ oxidation of the enolate formed upon
      conjugate addition, giving access to the corresponding alpha-hydroxy-beta,gamma
      diamino esters. Elaboration of these beta,gamma-diamino and alpha-hydroxy
      beta,gamma-diamino esters gave the protected forms of the 3-deoxy-3
      aminosphingoid base targets.

PMID- 29022338
TI  - Selective Double-Labeling of Cell-Free Synthesized Proteins for More Accurate
      smFRET Studies.
AB  - Forster resonance energy transfer (FRET) studies performed at the single molecule
      level have unique abilities to probe molecular structure, dynamics, and function
      of biological molecules. This technique requires specimens, like proteins,
      equipped with two different fluorescent probes attached at specific positions
      within the molecule of interest. Here, we present an approach of cell-free
      protein synthesis (CFPS) that provides proteins with two different functional
      groups for post-translational labeling at the specific amino acid positions.
      Besides the sulfhydryl group of a cysteine, we make use of an azido group of a p
      azido-l-phenylalanine to achieve chemical orthogonality. Herein, we achieve not
      only a site-specific but, most importantly, also a site-selective, label scheme
      that permits the highest accuracy of measured data. This is demonstrated in a
      case study, where we synthesize human calmodulin (CaM) by using a CFPS kit and
      prove the structural integrity and the full functionality of this protein.

PMID- 29022339
TI  - Resveratrol Ameliorates Tau Hyperphosphorylation at Ser396 Site and Oxidative
      Damage in Rat Hippocampal Slices Exposed to Vanadate: Implication of ERK1/2 and
      GSK-3beta Signaling Cascades.
AB  - The objective of this study was to investigate the effect of resveratrol (a
      natural polyphenolic phytostilbene) on tau hyperphosphorylation and oxidative
      damage induced by sodium orthovanadate (Na3VO4), the prevalent species of
      vanadium (vanadate), in rat hippocampal slices. Our results showed that
      resveratrol significantly inhibited Na3VO4-induced hyperphosphorylation of tau at
      the Ser396 (p-S396-tau) site, which is upregulated in the hippocampus of
      Alzheimer's disease (AD) brains and principally linked to AD-associated cognitive
      dysfunction. Subsequent mechanistic studies revealed that reduction of ERK1/2
      activation was involved in the inhibitory effect of resveratrol by inhibiting the
      ERK1/2 pathway with SL327 mimicking the aforementioned effect of resveratrol.
      Moreover, resveratrol potently induced GSK-3beta Ser9 phosphorylation and reduced
      Na3VO4-induced p-S396-tau levels, which were markedly replicated by pharmacologic
      inhibition of GSK-3beta with LiCl. These results indicate that resveratrol could
      suppress Na3VO4-induced p-S396-tau levels via downregulating ERK1/2 and GSK-3beta
      signaling cascades in rat hippocampal slices. In addition, resveratrol diminished
      the increased extracellular reactive oxygen species generation and hippocampal
      toxicity upon long-term exposure to Na3VO4 or FeCl2. Our findings strongly
      support the notion that resveratrol may serve as a potential nutraceutical agent
      for AD.

PMID- 29022340
TI  - Molecular Dynamics of Oxazole Yellow Dye in its Ground and First Excited
      Electronic States in Solution and when Intercalated in dsDNA.
AB  - Oxazole yellow (YOPRO), a cyanine dye consisting of benzoxazole and quinoline
      rings connected by a linker, is almost nonfluorescent in water, but its
      fluorescence is greatly enhanced after intercalation in double-stranded DNA,
      forming the basis of DNA concentration assays. To explore this difference, new
      potential energy surfaces for the two linker dihedral angles in the ground S0 and
      first excited S1 electronic states are developed. Umbrella sampling molecular
      dynamics is used to obtain the free energy of rotation around the two dihedral
      angles of the linker. The two-dimensional free energy surface of the S1 state,
      spanning the Franck-Condon transition point from the S0 electronic state minimum
      (dihedral 1 around 180 degrees , dihedral 2 around 0 degrees ) to the S1 state
      minimum (~90, ~0), is obtained in water and when intercalated. In water, YOPRO's
      S1 free energy surface is completely downhill from the Franck-Condon point,
      whereas when intercalated, there is a barrier on the path. Thus, when
      intercalated in DNA, S1 YOPRO is more constrained than in water, supporting the
      hypothesis that intercalation does inhibit ring rotational motion around the
      linker and therefore strongly reduces the nonradiative relaxation, resulting in
      higher fluorescence intensity.

PMID- 29022341
TI  - Computationally Guided Catalyst Design in the Type I Dynamic Kinetic Asymmetric
      Pauson-Khand Reaction of Allenyl Acetates.
AB  - The Rh(I)-catalyzed allenic Pauson-Khand reaction (APKR) is an efficient, redox
      neutral method of synthesizing alpha-acyloxy cyclopentenones. An enantioselective
      APKR could provide access to chiral, nonracemic alpha-acyloxy and alpha-hydroxy
      cyclopentenones and their corresponding redox derivatives, such as thapsigargin,
      a cytotoxic natural product with potent antitumor activity. Rapid scrambling of
      axial chirality of allenyl acetates in the presence of Rh(I) catalysts enables
      the conversion of racemic allene to enantiopure cyclopentenone product in a
      dynamic kinetic asymmetric transformation (DyKAT). A combined experimental and
      computational approach was taken to develop an effective catalytic system to
      achieve the asymmetric transformation. The optimization of the denticity, and
      steric and electronic properties of the ancillary ligand (initially (S)-MonoPhos,
      58:42 er), afforded a hemilabile bidentate (S)-MonoPhos-alkene-Rh(I) catalyst
      that provided alpha-acyloxy cyclopentenone product in up to 14:86 er.
      Enantioselectivity of the Rh(I)-(S)-MonoPhos-alkene catalyst was rationalized
      using ligand-substrate steric interactions and distortion energies in the
      computed transition states. This asymmetric APKR of allenyl acetates is a rare
      example of a Type I DyKAT reaction of an allene, the first example of DyKAT in a
      cyclocarbonylation reaction, and the first catalyst-controlled enantioselective
      APKR.

PMID- 29022342
TI  - Biodegradability of Plastics: Challenges and Misconceptions.
AB  - Plastics are one of the most widely used materials and, in most cases, they are
      designed to have long life times. Thus, plastics contain a complex blend of
      stabilizers that prevent them from degrading too quickly. Unfortunately, many of
      the most advantageous properties of plastics such as their chemical, physical and
      biological inertness and durability present challenges when plastic is released
      into the environment. Common plastics such as polyethylene (PE), polypropylene
      (PP), polystyrene (PS), and polyethylene terephthalate (PET) are extremely
      persistent in the environment, where they undergo very slow fragmentation
      (projected to take centuries) into small particles through photo-, physical, and
      biological degradation processes1. The fragmentation of the material into
      increasingly smaller pieces is an unavoidable stage of the degradation process.
      Ultimately, plastic materials degrade to micron-sized particles (microplastics),
      which are persistent in the environment and present a potential source of harm
      for organisms.

PMID- 29022343
TI  - Synthesis and Crystal Structure of Li+@Fluoreno[60]fullerene: Effect of
      Encapsulated Lithium Ion on Electrochemistry of Spiroannelated Fullerene.
AB  - The reaction of [Li+@C60]TFSI- (TFSI = bis(trifluoromethanesulfonyl)imide) with 9
      diazofluorene directly produced a [6,6]-adduct of lithium-ion-containing
      fluoreno[60]fullerene, [6,6]-[Li+@C60(fluoreno)]TFSI-, which was
      crystallographically characterized. Cyclic voltammetry of the compound showed a
      reversible one-electron reduction wave at -0.51 V (vs Fc/Fc+) and an irreversible
      reduction wave for the second electron. The latter was attributed to opening of
      the three-membered ring due to strong stabilization of the resulting sp3
      carbanion by the encapsulated Li+ and formation of a 14pi-electron aromatic
      fluorenyl anion.

PMID- 29022344
TI  - Development of Photoacoustic Probes for in Vivo Molecular Imaging.
AB  - Photoacoustic (PA) imaging is an emerging, non-invasive imaging modality that
      encompasses attributes of both optical and ultrasound imaging. Because of the
      combination of optical excitation and acoustic detection, PA imaging enables high
      contrast and high resolution within deep tissue (centimeter depths). Recent
      advances in PA probe development have allowed for stimulus-responsive imaging in
      a variety of biological models with implications for basic, translational, and
      clinical sciences. This perspective highlights recent progress in the development
      of PA probes and their application to live-animal molecular imaging.

PMID- 29022345
TI  - Single-Site Photocatalytic H2 Evolution from Covalent Organic Frameworks with
      Molecular Cobaloxime Co-Catalysts.
AB  - We demonstrate photocatalytic hydrogen evolution using COF photosensitizers with
      molecular proton reduction catalysts for the first time. With azine-linked N2-COF
      photosensitizer, chloro(pyridine)cobaloxime co-catalyst, and TEOA donor, H2
      evolution rate of 782 MUmol h-1 g-1 and TON of 54.4 has been obtained in a
      water/acetonitrile mixture. PXRD, solid-state spectroscopy, EM analysis, and
      quantum-chemical calculations suggest an outer sphere electron transfer from the
      COF to the co-catalyst which subsequently follows a monometallic pathway of H2
      generation from the CoIII-hydride and/or CoII-hydride species.

PMID- 29022347
TI  - Energy Efficiency and Performance Limiting Effects in Thermo-Osmotic Energy
      Conversion from Low-Grade Heat.
AB  - Low-grade heat energy from sources below 100  degrees C is available in massive
      quantities around the world, but cannot be converted to electricity effectively
      using existing technologies due to variability in the heat output and the small
      temperature difference between the source and environment. The recently developed
      thermo-osmotic energy conversion (TOEC) process has the potential to harvest
      energy from low-grade heat sources by using a temperature difference to create a
      pressurized liquid flux across a membrane, which can be converted to mechanical
      work via a turbine. In this study, we perform the first analysis of energy
      efficiency and the expected performance of the TOEC technology, focusing on
      systems utilizing hydrophobic porous vapor-gap membranes and water as a working
      fluid. We begin by developing a framework to analyze realistic mass and heat
      transport in the process, probing the impact of various membrane parameters and
      system operating conditions. Our analysis reveals that an optimized system can
      achieve heat-to-electricity energy conversion efficiencies up to 4.1% (34% of the
      Carnot efficiency) with hot and cold working temperatures of 60 and 20  degrees
      C, respectively, and an operating pressure of 5 MPa (50 bar). Lower energy
      efficiencies, however, will occur in systems operating with high power densities
      (>5 W/m2) and with finite-sized heat exchangers. We identify that the most
      important membrane properties for achieving high performance are an asymmetric
      pore structure, high pressure resistance, a high porosity, and a thickness of 30
      to 100 MUm. We also quantify the benefits in performance from utilizing deaerated
      water streams, strong hydrodynamic mixing in the membrane module, and high heat
      exchanger efficiencies. Overall, our study demonstrates the promise of full-scale
      TOEC systems to extract energy from low-grade heat and identifies key factors for
      performance optimization moving forward.

PMID- 29022346
TI  - Solid-State Fluorescence of Fluorine-Modified Carbon Nanodots Aggregates
      Triggered by Poly(ethylene glycol).
AB  - Solid-state fluorescent carbon quantum dots (QDs) can be used for the encryption
      of security information. Controlling the dispersion and aggregation of the QDs is
      crucial for switching their solid-state fluorescence "on" and "off." The use of
      polymers has been proposed to slightly separate the QDs inside aggregates to
      trigger their fluorescence. However, the complex interactions between the QDs and
      flexible polymer chains make this process challenging. Here, fluorine-modified
      carbon nanodots (FCDs) were used in a solution as the printing ink. After
      printing, the FCDs were aggregated on paper via hydrogen bonds, thereby quenching
      the fluorescence. After a poly(ethylene glycol) (PEG) treatment, the FCDs
      exhibited yellow solid-state fluorescence due to an increased interdot spacing.
      The fluorescence intensity and emission wavelength could be tuned by varying the
      molecular weight and quantity of PEG used. Finally, we demonstrated a high
      resolution encryption and decryption system based on the PEG-triggered
      fluorescence of FCDs.

PMID- 29022348
TI  - Modified Mesoporous Silica Nanoparticles with a Dual Synergetic Antibacterial
      Effect.
AB  - Application of mesoporous silica nanoparticles (MSNs) as
      antifouling/antibacterial carriers is limited and specifically with a dual
      synergetic effect. In the present work, MSNs modified with quaternary ammonium
      salts (QASs) and loaded with the biocide Parmetol S15 were synthesized as
      functional fillers for antifouling/antibacterial coatings. From the family of the
      MSNs, MCM-48 was selected as a carrier because of its cubic pore structure, high
      surface area, and high specific pore volume. The QASs used for the surface
      modification of MCM-48 were dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium
      chloride and dimethyltetradecyl[3-(triethoxysilyl)propyl]ammonium chloride. The
      QAS-modified MCM-48 reveals strong covalent bonds between the QAS and the surface
      of the nanoparticles. The surface functionalization was confirmed by Fourier
      transform infrared spectroscopy, thermogravimetric analysis, elemental analysis,
      and zeta-potential measurements. Additional loading of the QAS-modified MCM-48
      with a commercially available biocide (Parmetol S15) resulted in a synergetic
      dual antibacterial/antifouling effect. Either loaded or unloaded QAS-modified
      MSNs exhibited high antibacterial performance confirming their dual activity. The
      QAS-modified MCM-48 loaded with the biocide Parmetol S15 killed all exposed
      bacteria after 3 h of incubation and presented 100% reduction at the
      antibacterial tests against Gram-negative and Gram-positive bacteria.
      Furthermore, the QAS-modified MCM-48 without Parmetol S15 presented 77-89%
      reduction against the exposed Gram-negative bacteria and 78-94% reduction against
      the exposed Gram-positive bacteria. In addition, the modified MCM-48 was mixed
      with coating formulations, and its antifouling performance was assessed in a
      field test trial in northern Red Sea. All synthesized paints presented
      significant antifouling properties after 5 months of exposure in real seawater
      conditions, and the dual antifouling effect of the nanoparticles was confirmed.

PMID- 29022349
TI  - Degradation of Carbonyl Hydroperoxides in the Atmosphere and in Combustion.
AB  - Oxygenates with carbonyl and hydroperoxy functional groups are important
      intermediates that are generated during the autoxidation of organic compounds in
      the atmosphere and during the autoignition of transport fuels. In the
      troposphere, the degradation of carbonyl hydroperoxides leads to low-vapor
      pressure polyfunctional species that may precipitate in clouds and fog droplets
      or to the formation of secondary organic aerosols (SOAs). In combustion, the fate
      of carbonyl hydroperoxides is important for the performance of advanced
      combustion engines, especially for autoignition. A key fate of the carbonyl
      hydroperoxides is reaction with OH radicals, for which kinetics data are
      experimentally unavailable. Here, we study 4-hydroperoxy-2-pentanone
      (CH3C(?O)CH2CH(OOH)CH3) as a model compound to clarify the kinetics of OH
      reactions with carbonyl hydroperoxides, in particular H atom abstraction and OH
      addition reactions. With a combination of electronic structure calculations, we
      determine previously missing thermochemical data, and with multipath variational
      transition state theory (MP-VTST), a multidimensional tunneling (MT)
      approximation, multiple-structure anharmonicity, and torsional potential
      anharmonicity, we obtained much more accurate rate constants than the ones that
      can computed by conventional single-structure harmonic transition state theory
      (TST) and than the empirically estimated rate constants that are currently used
      in atmospheric and combustion modeling. The roles of various factors in
      determining the rates are elucidated. The pressure-dependent rate constants for
      the addition reaction are computed using system-specific quantum RRK theory. The
      calculated temperature range is 298-2400 K, and the pressure range is 0.01-100
      atm. The accurate thermodynamic and kinetics data determined in this work are
      indispensable in the global modeling of SOAs in atmospheric science and in the
      detailed understanding and prediction of ignition properties of hydrocarbons and
      alternative fuels.

PMID- 29022350
TI  - Sensitive and Accurate Quantitation of Phosphopeptides Using TMT Isobaric
      Labeling Technique.
AB  - Phosphorylation is an essential post-translational modification for regulating
      protein function and cellular signal transduction. Mass spectrometry (MS)
      combined with isobaric tandem mass tags (TMTs) has become a powerful platform for
      simultaneous, large-scale phospho-proteome site identification and quantitation.
      To improve the accuracy of isobaric tag-based quantitation in complex proteomic
      samples, MS3-based acquisition methods such as Synchronous Precursor Selection
      (SPS) have been used. However, the method suffers from lower peptide
      identification rates when applied to enriched phosphopeptide samples compared
      with unmodified samples due to differences in phosphopeptide fragmentation
      patterns during tandem MS. We developed and optimized two new acquisition methods
      for analysis of TMT-labeled multiplexed phosphoproteome samples, which resulted
      in more phosphopeptide identifications with less ratio distortion when compared
      with previous methods. We also applied these improved methods to a large-scale
      study of phosphorylation levels in A549 cell lines treated with insulin or
      insulin growth factor 1 (IGF-1). Overall, 3378 protein groups and 12 465
      phosphopeptides were identified, of which 10 436 were quantified across 10
      samples without prefractionation. The accurate measurement enabled us to map to
      numerous signaling pathways including mechanistic target of rapamycin (mTOR),
      epidermal growth factor receptor (EGFR, ErbB), and insulin signaling pathways.

PMID- 29022353
TI  - Chemical composition and in vitro antileishmanial and cytotoxic activities of the
      essential oils of Ocotea dispersa (Nees) Mez and Ocotea odorifera (Vell) Rohwer
      (Lauraceae).
AB  - We investigate the chemical composition and the in vitro antileishmanial and
      cytotoxic activities of the essential oils extracted from the leaves of Ocotea
      dispersa (Nees) Mez (OD-EO) and Ocotea odorifera (Vell) Rohwer (OO-EO). On the
      basis of GC-FID and GC-MS, alpha-eudesmol (20.9%), valencene (10.2%), delta
      elemene (9.3%) and isospathulenol (7.3%) are the major constituents of OD-EO,
      whereas safrole (36.3%), gamma-cadinene (6.6%), camphor (6.5%) and alpha-copaene
      (6.0%) are the main constituents of OO-EO. Both OD-EO and OO-EO display
      significant activity against the promastigote forms of Leishmania amazonensis,
      with IC50 values of 4.67 +/- 0.95 and 11.67 +/- 2.16 MUg/mL, respectively. The
      50% cytotoxic concentration (CC50) of OD-EO and OO-EO to mouse peritoneal
      macrophages is 26.77 +/- 4.06 and 49.52 +/- 1.04 MUg/mL, respectively. This is
      the first report on the chemical composition of the essential oil extracted from
      the leaves of O. dispersa. Our results suggest that OD-EO and OO-EO are a
      promising source of new antileishmanial agents.

PMID- 29022351
TI  - The role of Vimentin in Regulating Cell Invasive Migration in Dense Cultures of
      Breast Carcinoma Cells.
AB  - Cell migration and mechanics are tightly regulated by the integrated activities
      of the various cytoskeletal networks. In cancer cells, cytoskeletal modulations
      have been implicated in the loss of tissue integrity and acquisition of an
      invasive phenotype. In epithelial cancers, for example, increased expression of
      the cytoskeletal filament protein vimentin correlates with metastatic potential.
      Nonetheless, the exact mechanism whereby vimentin affects cell motility remains
      poorly understood. In this study, we measured the effects of vimentin expression
      on the mechano-elastic and migratory properties of the highly invasive breast
      carcinoma cell line MDA231. We demonstrate here that vimentin stiffens cells and
      enhances cell migration in dense cultures, but exerts little or no effect on the
      migration of sparsely plated cells. These results suggest that cell-cell
      interactions play a key role in regulating cell migration, and coordinating cell
      movement in dense cultures. Our findings pave the way toward understanding the
      relationship between cell migration and mechanics in a biologically relevant
      context.

PMID- 29022352
TI  - Asymmetric Oxidative Coupling of Phenols and Hydroxycarbazoles.
AB  - The first examples of asymmetric oxidative coupling of simple phenols and 2
      hydroxycarbazoles are outlined. Generation of a more vanadium catalyst by ligand
      design and by addition of an exogenous Bronsted or Lewis acid was found to be key
      to coupling the more oxidatively resistant phenols. The resultant vanadium
      complex is both more Lewis acidic and more strongly oxidizing. Good to excellent
      levels of enantioselectivity could be obtained, and simple trituration readily
      provided the products with >=95% ee.

PMID- 29022354
TI  - Three new isoflavones from the Pueraria montana var. lobata (Willd.) and their
      bioactivities.
AB  - Three new isoflavones, 7-acetyl-4',6-dimethoxy-isoflavone (1), 7-acetyl-4'
      hydroxy-6-methoxy-isoflavone (2) and 7-acetyl-6,8-dimethoxy-4'-hydroxy-isoflavone
      (3), together with five known flavones (4-8), were isolated from the Pueraria
      montana var. lobata (Willd.). Their structures were elucidated by spectroscopic
      methods, including extensive 1D- and 2D NMR techniques. Compounds 1-8 were
      evaluated for their anti-tobacco mosaic virus (anti-TMV) activities. The results
      showed that compounds 1 and 2 exhibited high anti-TMV activities with inhibition
      rates of 36.8 and 33.6%, respectively. The inhibition rates are higher than that
      of positive control. The other compounds also showed potential anti-TMV
      activities with inhibition rates in the range of 21.8~28.4%, respectively. The
      cytotoxicities of compounds 1-3 against five human tumour cell lines (NB4, A549,
      SHSY5Y, PC3 and MCF7) were also tested. The results revealed that compounds 1-3
      showed weak inhibitory activities against some tested human tumour cell lines
      with IC50 values in the range of 1.2-3.6 MUM.

PMID- 29022355
TI  - Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy
      as an Analytical Method to Investigate the Secondary Structure of a Model Protein
      Embedded in Solid Lipid Matrices.
AB  - Protein drugs may encounter conformational perturbations during the formulation
      processing of lipid-based solid dosage forms. In aqueous protein solutions,
      attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy
      can investigate these conformational changes following the subtraction of
      spectral interference of solvent with protein amide I bands. However, in solid
      dosage forms, the possible spectral contribution of lipid carriers to protein
      amide I band may be an obstacle to determine conformational alterations. The
      objective of this study was to develop an ATR FT-IR spectroscopic method for the
      analysis of protein secondary structure embedded in solid lipid matrices. Bovine
      serum albumin (BSA) was chosen as a model protein, while Precirol AT05 (glycerol
      palmitostearate, melting point 58 C) was employed as the model lipid matrix.
      Bovine serum albumin was incorporated into lipid using physical mixing, melting
      and mixing, or wet granulation mixing methods. Attenuated total reflection FT-IR
      spectroscopy and size exclusion chromatography (SEC) were performed for the
      analysis of BSA secondary structure and its dissolution in aqueous media,
      respectively. The results showed significant interference of Precirol ATO5 with
      BSA amide I band which was subtracted up to 90% w/w lipid content to analyze BSA
      secondary structure. In addition, ATR FT-IR spectroscopy also detected thermally
      denatured BSA solid alone and in the presence of lipid matrix indicating its
      suitability for the detection of denatured protein solids in lipid matrices.
      Despite being in the solid state, conformational changes occurred to BSA upon
      incorporation into solid lipid matrices. However, the extent of these
      conformational alterations was found to be dependent on the mixing method
      employed as indicated by area overlap calculations. For instance, the melting and
      mixing method imparted negligible effect on BSA secondary structure, whereas the
      wet granulation mixing method promoted more changes. Size exclusion
      chromatography analysis depicted the complete dissolution of BSA in the aqueous
      media employed in the wet granulation method. In conclusion, an ATR FT-IR
      spectroscopic method was successfully developed to investigate BSA secondary
      structure in solid lipid matrices following the subtraction of lipid spectral
      interference. The ATR FT-IR spectroscopy could further be applied to investigate
      the secondary structure perturbations of therapeutic proteins during their
      formulation development.

PMID- 29022356
TI  - Xylaropyrones B and C, new gamma-pyrones from the endophytic fungus Xylaria sp.
      SC1440.
AB  - Two new gamma-pyrones, xylaropyrones B (1) and C (2), together with three known
      compounds, xylaropyrone (3), annularin A (4) and annularin C (5), were isolated
      from solid cultures of the endophytic fungus Xylaria sp. SC1440. The structures
      of these compounds were determined mainly by analysis of their NMR spectroscopic
      data. The relative configurations of 1 and 2 were assigned on the basis of J
      based configurational analysis, and the absolute configurations were established
      by experimental and TDDFT calculated ECD spectra. The isolated compounds were
      evaluated for cytotoxic and tyrosinase inhibitory activity.

PMID- 29022357
TI  - Challenges in Screening for Pediatric Nonalcoholic Fatty Liver Disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated
      liver enzymes in children in the United States. Screening for NAFLD in children
      with obesity is recommended by several published guidelines, but the application
      of these recommendations in pediatric weight management programs is uncertain.
      Our study aimed to describe the screening practices for NAFLD in a large
      pediatric weight management program. During 2014, 1312 patients were seen, with a
      liver enzyme panel obtained in 847 (64.5%). Only 47/847 (5.5%) had elevated liver
      enzymes twice the upper limit of normal. Of the 47, 33 (70%) patients had
      persistently elevated liver enzymes. Of those 33, 22 (67%) had further
      exclusionary laboratory testing. Screening for NAFLD is challenging even in a
      pediatric weight management program with clearly established protocols. Those
      with elevated liver enzymes do not always complete recommended exclusionary
      testing. Barriers to completing further evaluation need to be addressed.

PMID- 29022358
TI  - Development of the Injury Perceptions Questionnaire (InjPQ).
AB  - OBJECTIVES: Injuries are major causes of morbidity and mortality in the
      population. Given the central role of perceptions in self-regulation of health
      conditions, it is important to investigate how they are perceived. This article
      describes the development of the Injury Perceptions Questionnaire (InjPQ).
      METHODS: A concurrent study in a diverse sample of injured individuals (n = 333).
      The internal structure and the reliability (Cronbach's alpha) of InjPQ sub-scales
      were explored by factor analyses. Relationships between injury perception
      dimensions and equivalent illness perception scales and outcome measures (self
      assessed health; physical, emotional and social functioning; depression, anxiety
      and somatisation; satisfaction with life) were investigated. RESULTS: The InjPQ
      was found to represent the following perception scales: injury identity composed
      of social and body part components, PTSD symptoms, Injury event, Injury specific
      emotions, Injured self-image, Positive consequences, Responsibility/guilt,
      Coping, Time distance, Dependency, Healthy self, External attributions and Injury
      risk factors. The reliability and construct validity of the scales were found
      adequate. CONCLUSIONS: Injury perceptions can be reliably measured. While partly
      overlapping with equivalent illness perception scales, the InjPQ depicts
      cognitive dimensions unique to injury that add significantly to explaining
      variance in outcomes. The InjPQ is recommended for research and clinical use as a
      measure of injury perceptions.

PMID- 29022359
TI  - Health risks in rural populations due to heavy metals found in agricultural soils
      irrigated with wastewater in the Alto Balsas sub-basin in Tlaxcala and Puebla,
      Mexico.
AB  - The aim of this study was to determine the hazard ratio (HQ), the risk index
      (HI), and the cancer risk index (CRI) for populations of adults and children
      exposed to ingestion, dermal contact and inhalation of heavy metals in
      agricultural soil. For these, the contents of Cd, Pb, Ni, Cu, Co, Cr, Zn, and the
      metalloid As were determined in soils of four zones of the sub-basin of Alto
      Balsas, during two different periods of the year. The average content of metals
      in the soil was 1.24, 14.77, 14.80, 13.06, 5.50, 17.65, 22.89, and 5.32 mg kg-1
      for Cd, Pb, Ni, Cu, Co, Cr, Zn, and As, respectively. The highest risk in terms
      of HQ and HI was for adults, especially for men who are affected through the
      skin, with Cd and Cr being the most dangerous. CRI values were within the
      allowable range, without posing problems for adult and child populations.

PMID- 29022360
TI  - New pyridocarbazole alkaloids from Strychnos nitida.
AB  - Phytochemical investigation of Strychnos nitida has led to the isolation of three
      new racemic pyridocarbazole alkaloids, (+/-)-stritidas A-C (1-3) and three known
      monoterpenoid indole alkaloids (4-6). Compounds 2 and 3 represent the first
      examples of pyridocarbazole alkaloids featuring an N-2-hydroxyethyl moiety. Their
      structures were determined by combined spectroscopic data (MS, UV, IR and NMR)
      and chemical methods.

PMID- 29022361
TI  - Interactions of quercetin with receptor tyrosine kinases associated with human
      lung carcinoma.
AB  - Lung cancer is a deadly form of cancer with high morbidity and mortality rates.
      Deregulated receptor tyrosine kinases (RTKs) are frequently associated with the
      formation and development of lung carcinoma. Quercetin is a major dietary
      flavonoid that has been shown to induce cell growth inhibition and apoptosis in
      human lung cancer cell lines. In the current study, four major overexpressed RTKs
      - EGFR, FGFR1, IGF1R and c-Met - involved in human lung cancer were investigated.
      Molecular docking was employed to identify the binding orientation and inhibitory
      potential of quercetin in these RTKs. Quercetin bound to the ATP binding pocket
      of these kinases exhibited good binding scores and interactions by establishing
      hydrogen, hydrophobic and pi-pi interactions with the hinge region and the DFG
      motif in the activation loop. Thus, quercetin could be further explored as a
      platform for developing specific or polypharmacological compounds targeting
      overexpressed RTKs in lung cancer.

PMID- 29022362
TI  - Narratives of health and illness: Arts-based research capturing the lived
      experience of dementia.
AB  - : Introduction This paper presents three artists' residencies in a geriatric
      medicine unit in a teaching hospital. The aim of the residencies was creation of
      new work of high artistic quality reflecting the lived experience of the person
      with dementia and greater understanding of service user experience of living with
      dementia. This paper also explores arts-based research methodologies in a medical
      setting. Method Arts-based research and narrative enquiry were the method used in
      this study. Artists had extensive access to service users with dementia, family
      carers and clinical team. Projects were created through collaboration between
      clinical staff, arts and health director, artist, patients and family carers.
      Each performance was accompanied by a public seminar discussing dementia.
      Evaluations were undertaken following each residency. The process of creating
      artistic responses to dementia is outlined, presented and discussed. Results The
      artworks were well received with repeat performances and exhibitions requested.
      Evaluations of each residency indicated increased understanding of dementia. The
      narratives within the artworks aided learning about dementia. The results are a
      new chamber music composition, a series of visual artworks created
      collaboratively between visual artist and patients and family carers and a dance
      film inspired by a dancer's residency, all created through narrative enquiry.
      DISCUSSION AND CONCLUSION: These projects support the role of arts-based research
      as creative process and qualitative research method which contributes to
      illuminating and exploring the lived experience of dementia. The arts act as a
      reflective tool for learning and understanding a complex health condition, as
      well as creating opportunities for increased understanding and public awareness
      of dementia. Issues arising in arts-based research in medical settings are
      highlighted, including ethical issues, the importance of service user narrative
      and multidisciplinary collaboration in arts and health practice and research.

PMID- 29022363
TI  - Development of pneumococcal vaccines over the last 10 years.
AB  - INTRODUCTION: Although significant improvements in the prevention of pneumococcal
      infections have been achieved in recent years, Streptococcus pneumoniae remains a
      leading cause of morbidity and mortality. To prevent S. pneumoniae infections,
      vaccines have been developed for several years. Areas covered: In this review,
      the most important emerging problems regarding pneumococcal conjugate vaccines
      (PCVs) are discussed in addition to the status of new vaccine design and
      development. Given the medical, social and economic relevance of pneumococcal
      diseases, the availability of effective and safe vaccines against S. pneumoniae
      is a key objective of public health. Expert opinion: Protein vaccines using
      agents different from capsular polysaccharides (CPs) or whole-cell vaccines seem
      to induce a broader immune response than PCVs and theoretically offer definitive
      solutions, as they can stimulate both humoral and cellular immunity. Moreover,
      these vaccines, particularly the whole-cell vaccine, are simpler to produce and
      significantly less expensive. However, the development of these preparations is
      very far from completion. It is highly likely that for a long time, no new safe
      and effective pneumococcal vaccines will be available. The best formulation of
      new pneumococcal vaccines has not been established. Consequently, an effort
      towards the expanded use of the available vaccines has to be made.

PMID- 29022364
TI  - Fast 'wandering' Takotsubo syndrome: atypical mixed evolution from apical to mid
      ventricular ballooning.
AB  - We report the case of a 53-year-old woman admitted for typical chest pain and a
      diagnosis of Takotsubo syndrome (TTS). Initial echocardiographic presentation was
      characterized by apical and mid-ventricular akinesis and basal hyper-kinesis.
      Unexpectedly, later after admission, echocardiography showed recovered apical
      akinesis with an apparent 'migration' of systolic dysfunction to mid-ventricular
      segment and hyper-kinesis of apical and basal segments. One week after admission,
      left ventricular contractility completely recovered and cardiac magnetic
      resonance imaging did not show signs of subendocardial late-enhancement and
      myocardial edema. Cases of TTS may therefore occasionally rapidly 'wander' within
      left ventricular segments, raising doubts over the so far used classification of
      left ventricular patterns of ballooning in subjects with TTS (typical/atypical).
      Apparently, different patterns can rapidly evolve into each other. The absence of
      late-enhancement at cardiac magnetic resonance imaging could hypothetically
      identify rapidly 'wandering' cases.

PMID- 29022365
TI  - Detection of new phenylpropanoids from Dendrobium chrysanthum.
AB  - Herba Dendrobii has been documented in the Compendium of Materia Medica, with
      special efficacy in nourishing Yin and treating diabetes. However, the chemical
      profile of Dendrobium chrysanthum Lindl. has not been reported yet. The
      compositions were analysed with UPLC/Q-TOF-MS/MS. 53 compounds were tentatively
      characterised, and 14 compounds might be new compounds. Some novel lactones of
      poly-phenylpropanoids were firstly detected, and di-p-hydroxyphenylpropionic
      acidic p-coumaric acid lactone, a new compound of the first example, was obtained
      and identified. UPLC/Q-TOF-MS/MS was a feasible and efficient method to discover
      the unique compounds in complex matrices of D. chrysanthum.

PMID- 29022366
TI  - Examining sociodemographic risk factors for Chlamydia trachomatis infection: a
      population-based cohort study.
AB  - AIM: Chlamydia trachomatis is the most prevalent bacterial sexually transmitted
      infection in developed nations and is an important public health concern. We
      aimed to assess the factors associated with testing and positivity of C.
      trachomatis in a large population. METHODS: A retrospective study of a large
      Canadian health region was undertaken using 2011 census and laboratory data.
      Demographic and socioeconomic data from the national household survey were linked
      to microbiologic data for C. trachomatis. Multivariable generalized estimating
      equation models were constructed to examine relative risk for C. trachomatis
      testing and positivity. RESULTS: For testing and positivity, female sex and
      younger age groups were associated with increased risk. University education and
      South Asian ethnicity were associated with lower risk of positivity. CONCLUSION:
      Incorporating socio-demographic factors will be critical to the success of future
      sexually transmitted infection public health programs.

PMID- 29022367
TI  - Maleic anhydride and chromone derivatives from the endophytic fungus BCC 54265
      (Botryosphaeriaceae).
AB  - A maleic anhydride derivative, botryoanhydride (1), and a chromone derivative,
      botryochromone (2), together with three known chromones, eugenitin (3), 6
      hydroxymethyleugenin (4) and 6-methoxymethyleugenin (5), were isolated from
      cultures of the endophytic fungus BCC 54265 of the family Botryosphaeriaceae. The
      structures were elucidated on the basis of NMR, HRMS and CD data. Compound 2
      showed weak cytotoxic activity to cancer cell-lines.

PMID- 29022368
TI  - The Impact of Environmental Design on Teamwork and Communication in Healthcare
      Facilities: A Systematic Literature Review.
AB  - The purpose of this systematic review is to investigate the current knowledge
      about the impact of healthcare facility design on teamwork and communication by
      exploring the relevant literature. Teamwork and communication are behavioral
      factors that are impacted by physical design. However, the effects of
      environmental factors on teamwork and communication have not been investigated
      extensively in healthcare design literature. There are no published systematic
      reviews on the current topic. Searches were conducted in PubMed and Google
      Scholar databases in addition to targeted design journals including Health
      Environmental Research & Design, Environment and Behavior, Environmental
      Psychology, and Applied Ergonomics. Inclusion criteria were (a) full-text English
      language articles related to teamwork and communication and (b) involving any
      healthcare built environment and space design published in peer-reviewed journals
      between 1984 and 2017. Studies were extracted using defined inclusion and
      exclusion criteria. In the first phase, 26 of the 195 articles most relevant to
      teamwork and 19 studies of the 147 were identified and reviewed to understand the
      impact of communication in healthcare facilities. The literature regarding the
      impact of built environment on teamwork and communication were reviewed and
      explored in detail. Eighteen studies were selected and succinctly summarized as
      the final product of this review. Environmental design, which involves nurses,
      support staff, and physicians, is one of the critical factors that promotes the
      efficiency of teamwork and collaborative communication. Layout design,
      visibility, and accessibility levels are the most cited aspects of design which
      can affect the level of communication and teamwork in healthcare facilities.

PMID- 29022369
TI  - Psychosocially Supportive Design: The Case for Greater Attention to Social Space
      Within the Pediatric Hospital.
AB  - OBJECTIVE: Models of patient and family-centered care advocate catering to
      psychosocial needs when designing healthcare facilities yet there is little
      evidence available to determine how the built environment can cater to
      psychosocial needs. This article highlights the obstacles to overcoming this
      knowledge deficit in the pursuit of evidence-based guidelines to inform social
      provisions within the pediatric hospital setting. It will propose a working
      definition for psychosocial space and identify new research directions to enhance
      understandings of the relationship between social space and well-being.
      BACKGROUND: While traditional multibed ward configurations afforded opportunities
      for peer support relationships to develop, both for patients and caregivers, the
      contemporary preference for single-occupancy rooms intensifies the need to
      critically examine social spaces within the pediatric hospital. METHODS: Research
      suggests a correlation between social support and well-being. This article
      reviews the research underpinning contemporary understandings of this
      relationship; it positions literature from sociology, environmental psychology,
      and evidence-based design to highlight the limitations of this knowledge and
      identify where additional research is required to inform evidence-based design
      guidelines for psychosocially supportive spaces within pediatric healthcare
      settings. CONCLUSIONS: Evidence regarding the therapeutic value of social support
      within the pediatric hospital is not sufficiently sophisticated or conclusive to
      inform guidelines for the provision of social space with pediatric hospitals.
      There is an urgent need for targeted research to inform evidence-based design
      guidelines; this will demand a broad disciplinary approach.

PMID- 29022370
TI  - Toxicity and immunomodulatory efficacy of biosynthesized silver myconanosomes on
      pathogenic microbes and macrophage cells.
AB  - Silver myconanosomes prepared from Alternaria brassicae may exhibit potential
      antimicrobial and immunomodulatory activity due to their inimitable character.
      The prepared myconanosomes were characterized by using differential light
      scattering, zeta potential, UV-visible spectroscopy and transmission electron
      microscopic analyses. Mycologically produced AgNPs were found as spherical and
      irregular shaped measuring size range between 55.4 and 70.23 nm. The
      antimicrobicidal activity of these AgNPs against pathogenic microbes was
      evaluated by agar well diffusion method. Results showed that AgNPs inhibit the
      growth of various bacteria and fungi, which may be due to the disruption of cell
      membranes, leakage of cytoplasm and DNA degradation. Cytotoxicity analysis of
      AgNPs on cell lines revealed its dose dependent effect. Moreover, significant
      increase of intracellular reactive oxygen species was characterized in AgNPs
      treated cells after 4 h of incubation. Thus, AgNPs may have a significant
      advantage over conventional antibiotics as microorganisms are acquiring
      resistance against the broad range of available antibiotics.

PMID- 29022371
TI  - External validation of acute-to-chronic models for estimation of reproductive
      toxicity to Daphnia magna.
AB  - We evaluated the predictivity and applicability of previously proposed models for
      the reproductive toxicity of chemicals to Daphnia magna [SAR QSAR Environ. Res.
      27:10, 833-850] by using external data from the United States Environmental
      Protection Agency database ECOTOX. These models were based on quantitative
      structure-activity-activity relationships (QSAARs) and a quantitative activity
      activity relationship (QAAR): the models can be categorized as acute-to-chronic
      models with (QSAAR) and without (QAAR) structural and physicochemical (e.g.
      distribution coefficients, log D) descriptors. We found that the QSAAR models
      were suitable for chemicals with an '-NH2 attached to aromatic carbon' sub
      structure, whereas the QAAR model was better for multicomponent compounds,
      coordination complexes, tin compounds and straight-chain primary amines. For
      chemicals with a known specific mode of action (e.g. pesticides and antibacterial
      agents and their derivatives), toxicity estimation within the acute-to-chronic
      framework requires special attention. We evaluated the applicability of the
      models on the basis of the descriptors in the models. We recommend that chemicals
      be pre-screened before their toxicities are estimated with these models: pre
      screening enabled the estimation of the toxicities of some chemicals within the
      applicability domains of the models.

PMID- 29022372
TI  - Machine learning-based models to predict modes of toxic action of phenols to
      Tetrahymena pyriformis.
AB  - The phenols are structurally heterogeneous pollutants and they present a variety
      of modes of toxic action (MOA), including polar narcotics, weak acid respiratory
      uncouplers, pro-electrophiles, and soft electrophiles. Because it is often
      difficult to determine correctly the mechanism of action of a compound,
      quantitative structure-activity relationship (QSAR) methods, which have proved
      their interest in toxicity prediction, can be used. In this work, several QSAR
      models for the prediction of MOA of 221 phenols to the ciliated protozoan
      Tetrahymena pyriformis, using Chemistry Development Kit descriptors, are
      reported. Four machine learning techniques (ML), k-nearest neighbours, support
      vector machine, classification trees, and artificial neural networks, have been
      used to develop several models with higher accuracies and predictive capabilities
      for distinguishing between four MOAs. They showed global accuracy values between
      95.9% and 97.7% and area under Receiver Operator Curve values between 0.978 and
      0.998; additionally, false alarm rate values were below 8.2% for training set. In
      order to validate our models, cross-validation (10-folds-out) and external test
      set were performed with good behaviour in all cases. These models, obtained with
      ML techniques, were compared with others previously reported by other
      researchers, and the improvement was significant.

PMID- 29022373
TI  - Psychological effects of exercise among adult women: The impact of menopausal
      status.
AB  - The psychological and physical benefits of regular physical activity are well
      established. but the majority of research to date has focussed on younger male
      samples. Two studies examined the impact of menopausal status on the ability of
      women to derive psychological benefits from exercise. Regular exercisers,
      assessed immediately following an exercise class. scored significantly lower on
      negative mood dimensions and higher on positive mood than did non-exercisers,
      regardless of menopausal status. Regular exercisers also showed significant
      improvements in mood state when assessed before and after a single exercise
      session; again this effect was independent of menopausal status. The results
      suggest that the acute mood-enhancing effects of exercise are maintained despite
      the endocrine changes associated with menopause. It is argued that encouraging
      menopausal women to adopt appropriate exercise patterns may assist in the
      alleviation of psychological distress as well as providing physical benefits.

PMID- 29022374
TI  - Social support and cardiovascular reactions to active laboratory stressors.
AB  - In order to examine the hypothesis that social support attenuates cardiovascular
      reactions to standard laboratory stressors. 60 male and 60 female undergraduates
      were first tested alone and then in one of three conditions: alone, or with a
      friend or a stranger present. Those tested with a partner, be it friend or
      stranger, displayed cardiovascular reactions of a similar magnitude to those who
      remained alone. Subsequent analysis following reallocation of subjects in the
      partnered conditions to groupings based on their ratings of how supportive or
      prying they found their partners did yield some effects. However, they occurred
      as interactive effects with sex, appeared on some cardiovascular indices but not
      others, and were modest in size, frequently failing to emerge as reliable on post
      hoc analysis. It was concluded that future tests of the social support-reactivity
      hypothesis need to be conducted in more realistic social settings.

PMID- 29022375
TI  - Quality of life in health care professionals: Burnout and its associated factors
      in hiv/aids related care.
AB  - Health care professionals working in HIV/AIDS are dedicated to providing quality
      care for their clients. They also need to care for themselves. This study
      examines why burnout occurs and how it may be prevented in the care of clients
      with HIV/AIDS. The sample of Australian HIV/AIDS health care professionals (n =
      84). consisted of 54 nurses, 16 doctors and 14 social workers. Respondents were
      divided into groups on the basis of their burnout scores. Members of the High
      Burnout group had higher levels of Anxiety, Stress and Stigma, were more likely
      to use External Coping Strategies and higher amounts of Tangible Support than
      members of the Low Burnout group. Subjects in the Low Burnout group were more
      likely to use Internal Coping Strategies, had greater Affiliation with the Gay
      Community, experienced greater Support Belonging and Relationship Satisfaction
      and Social Recognition and Reward than their counterparts in the High Burnout
      group. Support and job-related rewards may buffer and prevent experiences of
      burnout. Programmes to prevent burnout should include the teaching of coping
      skills and relaxation skills and should foster staff support and recognition.

PMID- 29022376
TI  - Social perception of aids in french general public: 1987-1990 Evolution in paris
      region.

PMID- 29022377
TI  - Editorial board page for "Psychology and Health", volume 9, number 4.
AB  - This is a scanned image of the original Editorial Board page(s) for this issue.

PMID- 29022378
TI  - Exploring teenagers' adaptive and maladaptive thinking in relation to the threat
      of hiv infection.
AB  - Teenagers' HIV-preventive cognitions were explored within a protection motivation
      theory framework. Five hundred and seven adolescent men and women from two
      cohorts (sixteen and eighteen) completed a confidential postal questionnaire. The
      effect of demographic variables, previous sexual experience and appraisal of
      threat and coping resources upon HIV-relevant cognitions was investigated using
      path analysis. Cognitions promoting (adaptive) and inhibiting (maladaptive)
      preventive behaviour were considered. Anticipated condom use, intention to limit
      number of sexual partners and willingness to consider an HIV antibody test were
      included as adaptive HIV-preventive cognitions. Coping appraisal measures were
      strongly associated with anticipated condom use but threat appraisal measures
      were not. Gender, previous sexual experience, coping appraisal measures and
      denial accounted for 33% of the variance in anticipated condom use. Overall the
      results provided qualified support for Protection Motivation Theory. Implications
      for health education are highlighted.

PMID- 29022379
TI  - Effects of a post-hospitalization group health education programme for patients
      with coronary heart disease.
AB  - Effects of a post-hospitolization group health education programme for patients
      with coronary heart disease. A health education programme was offered to groups
      of coronary heart patients and their partners after discharge from hospital. A
      randomized pre-test post-test control group design was used to evaluate the
      effects of this experimental intervention. The health education programme was
      offered to 109 coronary heart patients in groups of between five and eight
      patients together with their partners in addition to standard medical care and
      physical training. A control group of 108 patients received only standard medical
      care and physical training. The intervention consisted of eight weekly two-hour
      group health education sessions and one follow-up session. All sessions focused
      on the promotion of healthy habits and the reduction of adverse psychosocial
      consequences of the incident. In the short term (about four months after the
      incident) the health education programme showed statistically significant
      intervention effects on knowledge about coronary heart diseases, smoking
      cessation, healthy eating habits and the number of consultations with the family
      physician, but no effects on emotional distress. In the long term (one year after
      the incident) there was only a significant intervention effect on smoking
      cessation. These results suggest that the effects of the programme are modest,
      especially in terms of maintenance of behavioural change. As a consequence, it is
      suggested that the programme should not be offered to all coronary patients
      during cardiac rehabilitation, but only to those who can be expected to profit
      most from it.

PMID- 29022380
TI  - Curcumin or bisdemethoxycurcumin for nose-to-brain treatment of Alzheimer
      disease? A bio/chemo-informatics case study.
AB  - The current study introduces a new idea of utilising several bio/chemoinformatics
      tools in comparing two bio-similar natural molecules viz. curcumin and
      bisdemethoxycurcumin (BDMC) in order to select a potential nose-to-brain remedy
      for Alzheimer disease. The comparison comprised several bio/chemo informatics
      tools. It encompassed all levels starting from loading the drug in a certain
      carrier; PLGA nanoparticles, to the biopharmaceutical level investigating the
      interaction with mucin and inhibition of P-gp blood-brain barrier efflux pumps.
      Finally, the therapeutic level was investigated by studying the interaction with
      pharmacological targets such as amyloid peptide plaques and cyclooxygenase2
      enzyme responsible for the inflammatory reactions of the studied disease. The
      comparison revealed the superiority of curcumin over BDMC. Five new analogues
      were also hypothesised where diethoxybisdemethoxycurcumin was  recommended as a
      superior molecule. This work introduced the virtual utilisation of bio/chemo
      informatics tools as a reliable and economic alternative to the exhausting and
      resources-consuming wet-lab experimentation.

PMID- 29022381
TI  - Effects of probiotic bacteria on mucosal polyamines levels in dogs with IBD and
      colonic polyps: a preliminary study.
AB  - Spermine (SPM) and its precursor putrescine (PUT), regulated by ornithine
      decarboxylase (ODC) and diamino-oxidase (DAO), are polyamines required for cell
      growth and proliferation. Only a few studies have investigated the anti
      inflammatory and tumour inhibitory properties of probiotics on mucosal polyamine
      levels. We investigated the effects of a high concentration multistrain probiotic
      for human use on colonic polyamine biosynthesis in dogs. Histological sections
      (inflammatory bowel disease, n=10; polyposis, n=5) were assessed after receiving
      112 to 225*109 lyophilised bacteria daily for 60 days at baseline (T0) and 30
      days after treatment end (T90). Histology scores, expression of PUT, SPM, ODC and
      DAO, and a clinical activity index (CIBDAI) were compared at T0 and T90. In
      polyps, cellular proliferation (Ki-67 expression), and apoptosis (caspase-3
      protein expression) were also evaluated. After treatment, in inflammatory bowel
      disease significant decreases were observed for CIBDAI (P=0.006) and histology
      scores (P<0.001); PUT, SPM and ODC expression increased (P<0.01). In polyps, a
      significant decrease in polyamine levels, ODC activity, and Ki-67, and a
      significant increase in caspase-3 positivity and DAO expression (P=0.005) was
      noted. Our results suggest potential anti-proliferative and anti-inflammatory
      effects of the probiotic mixture in polyps and inflammation, associated with
      reduced mucosal infiltration and up-regulation of PUT, SPM, and ODC levels.

PMID- 29022382
TI  - Opposing effect of Lactobacillus on in vitro Klebsiella pneumoniae in biofilm and
      in an in vivo intestinal colonisation model.
AB  - Beneficial bacteria represent potential sources of therapy, particularly in the
      battle against antibiotic-resistant pathogens. The Gram-negative bacillus
      Klebsiella pneumoniae is not only a paradigm of multi-resistant opportunistic
      pathogen, but it is also able to colonise the human intestine and displays a high
      capacity to form biofilm. In this study, the anti-biofilm activity of 140
      neutralised Lactobacillus supernatants was assessed against K. pneumoniae. Among
      the 13 strains whose supernatant significantly impaired biofilm formation,
      Lactobacillus plantarum CIRM653 was selected because it was also able to impair
      K. pneumoniae preformed biofilm, independently of a bactericidal effect. Mixed K.
      pneumoniae/L. plantarum CIRM653 biofilms had reduced tridimensional structures
      associated with a significant decrease in K. pneumoniae biomass. Further
      investigation showed that L. plantarum CIRM653 supernatant induced
      transcriptional modifications of K. pneumoniae biofilm-related genes, including
      down-regulation of the quorum sensing-related lsr operons and over-expression of
      type 3 pili structure genes. Increased production of type 3 pili was validated by
      Western-blot, hemagglutination and adhesion assays. L. plantarum CIRM653 activity
      against K. pneumoniae was also assessed in a murine intestinal colonisation
      model: a constant faecal pathogen burden was observed, as against a gradual
      decrease in the control group. These results reveal that an in vitro a priori
      attracting anti-biofilm activity of Lactobacillus might be counterbalanced by an
      in vivo behaviour in a complex microbiota environment with potential deleterious
      dispersal of highly adherent K. pneumoniae cells, raising the question of the
      accuracy of in vitro assays in screening of beneficial microbes.

PMID- 29022383
TI  - Ratio of Klebsiella/Bifidobacterium in early life correlates with later
      development of paediatric allergy.
AB  - Several studies have reported that intestinal microbial colonisation patterns
      differ between non-allergic and allergic infants. However, the microbial
      signature underlying the pathogenesis of allergies remains unclear. We aim to
      gain insight into the development of the intestinal microbiota of healthy infants
      and infants who develop allergy in early life, and identify potential microbiota
      biomarkers of later allergic disease. Using a case-control design in a Chinese
      sub-cohort of a Singaporean birth cohort (GUSTO), we utilised 16S rRNA gene
      sequencing to assess intestinal microbial composition and diversity of 21
      allergic and 18 healthy infants at 3 weeks, 3 months and 6 months of age, and
      correlated the microbiota with allergy at ages 18 and 36 months. Pronounced
      differences in intestinal microbiota composition between allergic and healthy
      infants were observed at 3 months of age. The intestine of healthy infants was
      colonised with higher abundance of commensal Bifidobacterium. Conversely,
      Klebsiella, an opportunistic pathogen, was significantly enriched in the allergic
      infants. Interestingly, infants with a high Klebsiella/Bifidobacterium (K/B)
      ratio (above the population median K/B ratio) at age 3 months had an odds ratio
      of developing allergy by 3 years of age of 9.00 (95% confidence interval 1.46
      55.50) compared to those with low K/B ratio. This study demonstrated a
      relationship between the ratio of genera Klebsiella and Bifidobacterium during
      early infancy and development of paediatric allergy in childhood. Our study
      postulates that an elevated K/B ratio in early infancy could be a potential
      indicator of an increased risk of allergy development. This line of research
      might enable future intervention strategies in early life to prevent or treat
      allergy. Our study provides new insights into microbial signatures associated
      with childhood allergy, in particular, suggests that an elevated K/B ratio could
      be a potential early-life microbiota biomarker of allergic disease.

PMID- 29022384
TI  - Does the maternal vaginal microbiota play a role in seeding the microbiota of
      neonatal gut and nose?
AB  - The acquisition and early maturation of infant microbiota is not well understood
      despite its likely influence on later health. We investigated the contribution of
      the maternal microbiota to the microbiota of infant gut and nose in the context
      of mode of delivery and feeding. Using 16S rRNA sequencing and specific qPCR, we
      profiled microbiota of 42 mother-infant pairs from the GUSTO birth cohort, at
      body sites including maternal vagina, rectum and skin; and infant stool and nose.
      In our study, overlap between maternal vaginal microbiota and infant faecal
      microbiota was minimal, while the similarity between maternal rectal microbiota
      and infant microbiota was more pronounced. However, an infant's nasal and gut
      microbiota were no more similar to that of its own mother, than to that of
      unrelated mothers. These findings were independent of delivery mode. We conclude
      that the transfer of maternal vaginal microbes play a minor role in seeding
      infant stool microbiota. Transfer of maternal rectal microbiota could play a
      larger role in seeding infant stool microbiota, but approaches other than the
      generally used analyses of community similarity measures are likely to be needed
      to quantify bacterial transmission. We confirmed the clear difference between
      microbiota of infants born by Caesarean section compared to vaginally delivered
      infants and the impact of feeding mode on infant gut microbiota. Only vaginally
      delivered, fully breastfed infants had gut microbiota dominated by
      Bifidobacteria. Our data suggest that reduced transfer of maternal vaginal
      microbial is not the main mechanism underlying the differential infant microbiota
      composition associated with Caesarean delivery. The sources of a large proportion
      of infant microbiota could not be identified in maternal microbiota, and the
      sources of seeding of infant gut and nasal microbiota remain to be elucidated.

PMID- 29022385
TI  - Effect of antibiotic, probiotic, and human rotavirus infection on colonisation
      dynamics of defined commensal microbiota in a gnotobiotic pig model.
AB  - We developed a gnotobiotic (Gn) pig model colonised with defined commensal
      microbiota (DMF) to provide a simplified and controlled system to study the
      interactions between intestinal commensals, antibiotics (ciprofloxacin, CIP),
      probiotics (Escherichia coli Nissle 1917, EcN) and virulent human rotavirus
      (VirHRV). The DMF included seven gut commensal species of porcine origin that
      mimic the predominant species in the infant gut. Gn piglets were divided into
      four groups: DMF control (non-treated), DMF+CIP (CIP treated), DMF+CIP+EcN
      (CIP/EcN treated), DMF+EcN (EcN treated) and inoculated orally with 105 cfu of
      each DMF strain. The pig gut was successfully colonised by all DMF species and
      established a simplified bacterial community by post-bacteria colonisation day
      (PBCD) 14/post-VirHRV challenge day (PCD) 0. Overall, Bifidobacterium
      adolescentis was commonly observed in faeces in all groups and time points. At
      PCD0, after six days of CIP treatment (DMF+CIP), we observed significantly
      decreased aerobic and anaerobic bacteria counts especially in jejunum (P<0.001),
      where no DMF species were detected in jejunum by T-RFLP. Following HRV challenge,
      100% of pigs in DMF+CIP group developed diarrhoea with higher diarrhoea scores
      and duration as compared to all other groups. However, only 33% of pigs treated
      with EcN plus CIP developed diarrhoea. EcN treatment also enhanced the bacterial
      diversity and all seven DMF species were detected with a higher proportion of
      Bifidobacterium longum in jejunum in the DMF+CIP+EcN group on PBCD14/PCD0. Our
      results suggest that EcN increased the proportion of B. longum especially in
      jejunum and mitigated adverse impacts of antibiotic use during acute-infectious
      diarrhoea. The DMF model with a simplified gut commensal community can further
      our knowledge of how commensals and probiotics promote intestinal homeostasis and
      contribute to host health.

PMID- 29022386
TI  - Bacillus toyonensis improves immune response in the mice vaccinated with
      recombinant antigen of bovine herpesvirus type 5.
AB  - Probiotics modulate the immune response and can increase the effectiveness of
      vaccines. Bacillus toyonensis is widely used as a probiotic in animal feed. The
      aim of this study was to assess the effects of B. toyonensis administration on
      the immune response to an experimental recombinant vaccine against bovine
      herpesvirus type 5 (BoHV-5) in mice. Mice were vaccinated with BoHV-5 recombinant
      glycoprotein D and supplemented with the probiotic B. toyonensis in two regimes:
      one group received the probiotic only during seven days prior to the initial
      vaccination while the second group was given the probiotic throughout the
      experimental period of seven weeks. Animals supplemented with probiotic B.
      toyonensis in two regimes showed an increase in total immunoglobulin (Ig)G, IgG1
      and IgG2a levels in serum, in addition to higher titres of antibodies capable of
      neutralising the BoHV-5 virus than non-supplemented animals (P<0.05). Splenocytes
      from the supplemented mice had higher mRNA transcription levels of cytokines
      interleukin (IL)-4 and IL-12. These results show that the use of this probiotic
      may significantly contribute to the response elicited by recombinant vaccines,
      especially those that rely on increasing antibody and cell-mediated immune
      responses for efficacy. Further, the data support an immunomodulatory effect for
      probiotic B. toyonensis and imply that enhance effect on the immune response
      against a BoHV-5 recombinant vaccine in mice.

PMID- 29022387
TI  - Lactobacillus plantarum IS-10506 supplementation reduced SCORAD in children with
      atopic dermatitis.
AB  - Lactobacillus plantarum IS-10506 is a novel probiotic isolated from dadih, an
      Indonesian traditional fermented buffalo milk. It's in vitro and in vivo
      probiotic properties have been assessed. Probiotic function has been shown in
      vivo by the suppression of allergic reactions in BALB/c mice through the action
      of T-regulatory cells cytokines by balancing Th1 and Th2 immune response. Atopic
      dermatitis (AD) is a chronic recurrent inflammatory skin disease characterised by
      the imbalance of Th1 and Th2. The aim of the study was to assess the probiotic
      function of L. plantarum IS-10506 in children with mild and moderate AD. A
      randomised double-blind placebo-controlled trial comparing microencapsulated L.
      plantarum IS-10506 (1010 cfu/day) and placebo (skim milk-Avicel) twice daily for
      12 weeks was conducted in an outpatient clinic on children with mild and moderate
      AD. The trial included 22 AD children divided into intervention and control
      groups of n=12 and n=10 patients, respectively. Scoring Atopic Dermatitis Index
      (SCORAD) and serum immunoglobulin E (IgE), interleukin (IL)-4, interferon gamma
      (IFN-gamma), forkhead box P3 (Foxp3+)/IL-10, and IL-17 levels were assessed.
      Demographic and baseline characteristics were not significantly different between
      the two groups. SCORAD and levels of IL-4, IFN-gamma, and IL-17 were
      significantly lower in the probiotic group than those in the placebo group, while
      the IgE levels were not significantly changed. The ratio of Foxp3+ to IL-10 was
      significantly higher in the probiotic group than that in placebo group.
      Supplementation with the probiotic L. plantarum IS-10506 offered a potential
      treatment for children with AD. Further long-term studies with a larger sample
      size are required to confirm the therapeutic efficacy of L. plantarum IS-10506 in
      AD.

PMID- 29022388
TI  - Our gut microbiota: a long walk to homeostasis.
AB  - The microbiome of the human gastrointestinal tract (GIT) consists of billions of
      bacteria, fungi and viruses, of which bacteria play the most important role in
      nutrition, immune development, production of vitamins and maintaining a well
      balanced (homeostatic) microbial population. Many papers have been published on
      the microbiota in the human GIT, but little is known about the first group of
      bacteria that colonises an infant. The intestinal tract of an unborn is, despite
      general belief, not sterile, but contains bacteria that have been transferred
      from the mother. This opens a new research field and may change our understanding
      about the role bacteria play in early life, the selection of strains with
      probiotic properties and the treatment of diseases related to bacterial
      infections. Differences in bacterial populations isolated from meconia may
      provide answers to the prevention of certain forms of diabetes. More research is
      now focusing on the effect that a genetically diverse group, versus a much
      simpler microbial population, may have on the development of a homeostatic gut
      microbiome. The effect different bacterial species have on the gut-associated
      lymphoid tissue and cascade of immune responses has been well researched, but we
      still fail in identifying the ideal group of intestinal bacteria and if we do, it
      will certainly not be possible to maintain homeostasis with so many challenges
      the gut faces. Changes in diet, antibiotics, food preservatives and stress are
      some of the factors we would like to control, but more than often fail to do so.
      The physiology and genetics of the GIT changes with age and so the microbiome.
      This review summarises factors involved in the regulation of a gut microbiome.

PMID- 29022389
TI  - The composition and metabolism of faecal microbiota is specifically modulated by
      different dietary polysaccharides and mucin: an isothermal microcalorimetry
      study.
AB  - The metabolic activity of colon microbiota is specifically affected by fibres
      with various monomer compositions, degree of polymerisation and branching. The
      supply of a variety of dietary fibres assures the diversity of gut microbial
      communities considered important for the well-being of the host. The aim of this
      study was to compare the impact of different oligo- and polysaccharides (galacto-
      and fructooligosaccharides, resistant starch, levan, inulin, arabinogalactan,
      xylan, pectin and chitin), and a glycoprotein mucin on the growth and metabolism
      of faecal microbiota in vitro by using isothermal microcalorimetry (IMC). Faecal
      samples from healthy donors were incubated in a phosphate-buffered defined medium
      with or without supplementation of a single substrate. The generation of heat was
      followed on-line, microbiota composition (V3-V4 region of the 16S rRNA using
      Illumina MiSeq v2) and concentrations of metabolites (HPLC) were determined at
      the end of growth. The multiauxic power-time curves obtained were substrate
      specific. More than 70% of all substrates except chitin were fermented by faecal
      microbiota with total heat generation of up to 8 J/ml. The final metabolite
      patterns were in accordance with the microbiota changes. For arabinogalactan,
      xylan and levan, the fibre-affected distribution of bacterial taxa showed clear
      similarities (e.g. increase of Bacteroides ovatus and decrease of Bifidobacterium
      adolescentis). The formation of propionic acid, an important colon metabolite,
      was enhanced by arabinogalactan, xylan and mucin but not by galacto- and
      fructooligosaccharides or inulin. Mucin fermentation resulted in acetate,
      propionate and butyrate production in ratios previously observed for faecal
      samples, indicating that mucins may serve as major substrates for colon microbial
      population. IMC combined with analytical methods was shown to be an effective
      method for screening the impact of specific dietary fibres on functional changes
      in faecal microbiota.

PMID- 29022390
TI  - Randomised double blind placebo controlled trial on Lactobacillus reuteri DSM
      17938: improvement in symptoms and bowel habit in functional constipation.
AB  - Dysbiosis may contribute to constipation and its symptoms, therefore probiotic
      administration could improve significantly gut health and functions. The aim of
      the study was to investigate the effects of a long-lasting administration of
      Lactobacillus reuteri DSM 17938 (LR DSM 17938) on symptoms and quality of life
      (QoL) score in patients with functional constipation (FC). 56 FC patients with
      normal colonic transit time and without anorectal disorders and pelvic floor
      dysfunctions completed the study. LR DSM 17938 was administered for 105 days in a
      randomised double-blind clinical trial (28 patients per arm). Individual and
      cumulative scores including the Constipaq, a modified Constipation Scoring System
      (CSS) that considers the patient assessment of constipation-QoL (PAC-QoL), were
      calculated during the preliminary visit (V0), at day 15 (end of the induction
      period with a LR DSM 17938 double dosage, 4*108 cfu), day 60 (intermediate
      evaluation) and day 105 (V4) after a standard dosage (2*108 cfu). At the end of
      treatment, the beneficial effect of LR DSM 17938 compared to placebo was
      significantly evident for symptoms related to gas content and dysbiosis
      (abdominal discomfort, pain and bloating), incomplete defecation and helps for
      defecation (P<0.05). At the end of the whole LR DSM 17938 treatment, a marked and
      positive effect on both the CSS single and the cumulative items was evident with
      the exception of unfruitful attempt and Bristol score. Present findings indicate
      that LR DSM 17938 has an effect on symptoms different from stool consistency, and
      they suggest that this probiotic can effectively be used in association therapy
      rather than as single-drug therapy in the management of FC.

PMID- 29022392
TI  - Lay beliefs about the efficacy of self-reliance, seeking help and external
      control as strategies for overcoming obesity, drug addiction, marital problems,
      stuttering and insomnia.
AB  - This study was concerned with peoples' beliefs about the importance of twenty
      four different contributors towards overcoming five relatively common personal
      health problems, namely: obesity, drug addiction, marital difficulties,
      stuttering and insomnia. One hundred and twenty-two subjects completed a five
      page questionnaire indicating how effective each of these contributors were to
      overcoming the problems as specified. Factor analysis revealed an interpretable
      structure similar to previous studies (Luk and Bond, 1992): the emerging three
      factors were labelled 'self-reliance", "seeking help" and "external control".
      Multiple regression showed that few individual difference variables as measured
      were related to perceived relevance of the different contributors. The results
      were discussed in terms of subjects' beliefs concerning the value of self
      reliance as opposed to seeking help, and in relation to the importance of
      understanding lay beliefs about the efficacy of different forms of intervention.

PMID- 29022391
TI  - KR-12-a5 is a non-cytotoxic agent with potent antimicrobial effects against oral
      pathogens.
AB  - This study evaluated the cytotoxicity and antimicrobial activity of analogs of
      cationic peptides against microorganisms associated with endodontic infections. L
      929 fibroblasts were exposed to LL-37, KR-12-a5 and hBD-3-1CV and chlorhexidine
      (CHX, control), and cell metabolism was evaluated with MTT. The minimal
      inhibitory concentration (MIC) and the minimal bactericidal/fungicidal
      concentration (MBC/MFC) of the peptides and CHX were determined against oral
      pathogens associated with endodontic infections. Enterococcus faecalis and
      Streptococcus mutans biofilms were cultivated in bovine dentin blocks, exposed to
      different concentrations of the most efficient antimicrobial peptide and analyzed
      by confocal laser scanning microscopy. CHX and peptides affected the metabolism
      of L-929 at concentrations > 31.25 and 500 MUg ml-1, respectively. Among the
      peptides, KR-12-a5 inhibited growth of both the microorganisms tested with the
      lowest MIC/MBC/MFC values. In addition, KR-12-a5 significantly reduced E.
      faecalis and S. mutans biofilms inside dentin tubules. In conclusion, KR-12-a5 is
      a non-cytotoxic agent with potent antimicrobial and anti-biofilm activity against
      oral pathogens associated with endodontic infections.

PMID- 29022394
TI  - Effects of different psychological interventions on neck, shoulder and low back
      pain in female hospital staff.
AB  - One hundred and eleven females volunteered to take part in this intervention
      study of musculoskeletal pain. They all completed a survey of pain among five
      hundred and eighty-six female hospital staff and presented mild to severe pain in
      the neck, shoulder and/or low back. They were randomly assigned to one of the
      following groups; Focus on job-stress and psychosocial coping (Cognitive),
      relaxation training (Relaxation), the combination of the two (Combined) or to a
      control group (Control). Musculoskeletal pain (intensity and duration) was
      assessed by self-report prior to interventions, immediately after interventions,
      and at a four months follow-up. Results from multivariate analyses of variance as
      well as covariance (pre-intervention levels of pain as covariate) showed that
      magnitude of pain reduction was dependent upon the interaction between area of
      the back and type of intervention. These trends were more significant for
      intensity than for duration scores. They were due to reductions of pain in (1)
      neck and shoulders for the Cognitive and Combined groups and (2) in the low back
      and shoulders for the Relaxation group. The four month follow-up assessment
      revealed a significant risk of relapse only for duration of low back pain among
      subjects in the Combined group. Results from the Cognitive approach to
      intervention may reflect a causal role for ability to cope with psychosocial job
      stress in the development of neck and shoulder pain in female hospital staff.

PMID- 29022395
TI  - Superhealth basic: Development and evaluation of a low-cost community-based
      lifestyle change programme.
AB  - This research describes the development and evaluation of a community-based
      lifestyle change health promotion programme in New Zealand. The six-week small
      group programme, called Superhealth Basic, comes as a low-cost resource kit
      capable of widespread distribution in the community. It is based on a combination
      of health and community psychology principles and methods, and is designed to be
      run by untrained lay leaders. A quasi-experimental trial involving 141
      participants in 19 groups produced results showing significant positive changes
      in behaviour, health and wellbeing, with a high level of participant satisfaction
      and low dropout rates. At 12-month follow-up, the benefits of the programme were
      found to have been maintained with continuing expression of satisfaction with the
      programme. As a result of this research, Superhealth Basic is now available as a
      community resource throughout New Zealand.

PMID- 29022396
TI  - Gender differences in the psychological correlates of body-weight in young
      adults.
AB  - This study investigated gender differences in the correlates of actual and
      perceived body weight in a sample of young adults, as opposed to the college
      students usually sampled. Although women were significantly less overweight than
      men on an objective index of weight (the Body Mass Index). they perceived
      themselves to be significantly more overweight. The extent to which women
      perceived themselves as overweight was correlated negatively with self-esteem,
      and positively with negative affect including depressed mood, and minor
      psychiatric symptomology. In contrast, there was no relationship between body
      weight perception and psychological well-being for the men. It was concluded that
      a woman's body weight is much more central to her self-image than is a man's.

PMID- 29022397
TI  - Effective recruitment of parents into family-focused prevention research: A
      comparison of two strategies.
AB  - Recent literature highlights the need for more effective recruitment and
      retention strategies in prevention research. This article reports an
      investigation of the effectiveness of two recruitment strategies for a family
      focused substance abuse prevention study. The first strategy offered prospective
      participants two points at which they could make a decision about their level of
      involvement in the research project and required only a limited initial time
      commitment. The second strategy required an initial commitment to participate in
      all phases of the project. The investigation was conducted with 208 rural
      families participating in the pilot phase of a five-year prevention study. There
      were three primary findings. First, both strategies were effective, yielding
      higher recruitment rates than would be predicted from relevant literature.
      Second, the strategy requiring a limited time commitment showed significantly
      higher rates of recruitment into the pretest, but was associated with
      significantly lower posttest retention rates. Third, data trends emerged but
      there were no statistically significant differences between the two recruitment
      strategy groups across a range of intervention participation indicators.

PMID- 29022398
TI  - Editorial board page for "Psychology and Health", volume 9, number 5.
AB  - This is a scanned image of the original Editorial Board page(s) for this issue.

PMID- 29022399
TI  - Personality and attitudinal correlates of healthy and unhealthy lifestyles in
      young adults.
AB  - The relationship between healthy lifestyle and personality and attitudinal
      variables was analyzed with data collected from 809 men and 996 women aged 18-30
      years in England, Belgium, Finland and Norway as part of the European Health and
      Behaviour Survey. A health practices index was constructed on the basis of
      performance of sixteen behaviours including smoking, alcohol consumption,
      exercise, sleep time and a variety of dietary and preventive practices. Scores on
      the health practices index were higher in women than men, but in both sexes the
      index was normally distributed. Consistently healthy practices were positively
      correlated with extraversion and optimism, and negatively associated with
      neuroticism, psychoticism and chance locus of control beliefs. These effects were
      maintained after controlling for social desirability, but together accounted for
      only a modest proportion of the variance in the health practices index. The
      results are discussed in relation to the factors characterising health conscious
      and unhealthy lifestyles.

PMID- 29022400
TI  - Formulation optimization and the absorption mechanisms of nanoemulsion in
      improving baicalin oral exposure.
AB  - OBJECTIVE: The aim of this study was to optimize baicalin nanoemulsion, clarify
      the absorption mechanisms of nanoemulsion improving the exposure of baicalin, and
      assess the potential of employing nanoemulsion as nanosystem for insoluble drugs.
      SIGNIFICANCE: A novel nanoemulsion formulation was successfully prepared to
      enhance oral exposure of baicalin. METHODS: Pseudo-ternary phase diagrams were
      utilized to evaluate nanoemulsion area. Physicochemical properties of optimal
      nanoemulsion formulation were investigated. The exposure of baicalin from the
      nanoemulsion was compared with baicalin suspension. The in situ single-pass
      intestine perfusion (SPIP) method and chylomicron-blocked rat model were used to
      study the absorption mechanisms of nanoemulsion. RESULTS: Baicalin nanoemulsion
      was nearly spherical in shape with the average droplet size of 58.43 nm, and the
      zeta potential was -8.18 +/- 1.2 mV. The stability test showed that baicalin
      nanoemulsion was very stable. Pharmacokinetic study indicated that baicalin
      nanoemulsion showed 14.56-fold improvement in exposure in comparison to baicalin
      suspension. The results of SPIP and chylomicron flow blocking study showed that
      intestinal absorption and lymphatic transport process contributed to its systemic
      exposure. CONCLUSIONS: Based on the results, optimal nanoemulsion might be
      promising nanosystems for oral delivery of baicalin to satisfy clinical
      requirements.

PMID- 29022401
TI  - Green synthesis of silver nanoparticles using transgenic Nicotiana tabacum callus
      culture expressing silicatein gene from marine sponge Latrunculia oparinae.
AB  - In the present investigation, transgenic tobacco callus cultures and plants
      overexpressing the silicatein gene LoSilA1 from marine sponge Latrunculia
      oparinae were obtained and their bioreduction behaviour for the synthesis of
      silver nanoparticles (AgNPs) was studied. Synthesized nanoparticles were
      characterized using UV-visible spectroscopy, Fourier transformed infrared
      spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM),
      energy-dispersive X-ray spectroscopy (EDX), atomic flame electron microscopy
      (AFM) and nanoparticle tracking analysis (NTA). Our measurements showed that the
      reduction of silver nitrate produced spherical AgNPs with diameters in the range
      of 12-80 nm. The results of XRD analysis proved the crystal nature of the
      obtained AgNPs. FTIR analysis indicated that particles are reduced and stabilized
      in solution by the capping agent, which is likely to be proteins present in the
      callus extract. Interestingly, the reduction potential of LoSiLA1-transgenic
      callus line was increased three-fold compared with the empty vector-transformed
      calli. The synthesized AgNPs were found to exhibit strong antibacterial activity
      against Escherichia coli and Agrobacterium rhizogenes. The present study reports
      the first evidence for using genetic engineering for activation of the reduction
      potential of plant cells for synthesis of biocidal AgNPs.

PMID- 29022402
TI  - Antibiotics exposure and risk of inflammatory bowel disease: a systematic review.
AB  - AIM: The aim of this study was to critically assess all available evidence
      suggesting an association between antibiotic exposure and new onset of
      inflammatory bowel disease (IBD). MATERIALS AND METHODS: This systematic review
      was conducted according to the PRISMA statement and eligible studies were
      identified through search of PubMed, Embase and the Cochrane Library. Data on
      patient demographics, antibiotic exposure and confounding factors were analyzed.
      The Newcastle-Ottawa Scale (NOS) was used to assess the quality of eligible
      studies. RESULTS: A total of 15 observational studies (10 case control and five
      cohort) including 8748 patients diagnosed with IBD were systematically reviewed.
      Antibiotic exposure was mostly associated with Crohn's disease but not with
      ulcerative colitis. In particular, penicillin's, cephalosporins, metronidazole
      and fluoroquinolones were most commonly associated with the onset of Crohn's
      disease. The impact of tetracycline-family antibiotics on the pathogenesis of IBD
      was not clear. CONCLUSION: There may be an association between antibiotic
      exposure and the development of IBD; especially Crohn's disease. Even though,
      clinicians should be cautious when prescribing certain antibiotic regimens to
      patients with a strong family history of IBD, it should be emphasized that
      available data are not granular enough to reach any definitive conclusions.

PMID- 29022403
TI  - Developmental Approach for Behavior Learning Using Primitive Motion Skills.
AB  - Imitation learning through self-exploration is essential in developing
      sensorimotor skills. Most developmental theories emphasize that social
      interactions, especially understanding of observed actions, could be first
      achieved through imitation, yet the discussion on the origin of primitive
      imitative abilities is often neglected, referring instead to the possibility of
      its innateness. This paper presents a developmental model of imitation learning
      based on the hypothesis that humanoid robot acquires imitative abilities as
      induced by sensorimotor associative learning through self-exploration. In
      designing such learning system, several key issues will be addressed: automatic
      segmentation of the observed actions into motion primitives using raw images
      acquired from the camera without requiring any kinematic model; incremental
      learning of spatio-temporal motion sequences to dynamically generates a
      topological structure in a self-stabilizing manner; organization of the learned
      data for easy and efficient retrieval using a dynamic associative memory; and
      utilizing segmented motion primitives to generate complex behavior by the
      combining these motion primitives. In our experiment, the self-posture is
      acquired through observing the image of its own body posture while performing the
      action in front of a mirror through body babbling. The complete architecture was
      evaluated by simulation and real robot experiments performed on DARwIn-OP
      humanoid robot.

PMID- 29022405
TI  - European General Practice Research Network (EGPRN)Abstracts from the EGPRN
      conference in Riga, Latvia, 11?14 May 2017. Theme: 'Reducing the risk of chronic
      diseases in general practice/family medicine'.

PMID- 29022404
TI  - The significance of breastfeeding on sleep patterns during the first 48 hours
      postpartum for first time mothers.
AB  - Postpartum women sleep less during the early days following delivery. Long-term
      sleep disturbance and fatigue can have significant implications for physical and
      mental health, relationships, employment and parental competence. Most studies
      focus on the quality and quantity of maternal sleep between weeks one and six
      postpartum. We explored sleep patterns and reasons for wakefulness of first-time
      mothers immediately following delivery. Thirty first-time mothers completed a
      postnatal sleep questionnaire, detailing their total sleep time (TST), the
      reasons for being awake and their level of fatigue. The logs were completed in
      real time during the first 48 h postpartum, while they were still in a hospital
      environment. The data collected from the mothers in the study indicated that the
      mean TST in the first 48 h was 9.7 h. Of the factors explored only breastfeeding
      influenced the TST. Breastfeeding women slept on average 2.6 h longer than women
      who bottle-fed (p = .042). Impact statement What is already known on this
      subject: Childbearing affects women's sleep in many ways. Hormonal changes during
      pregnancy and postpartum as well as physiological and anatomical alterations, and
      the process of adaptation to the new parent's responsibilities contribute to
      changes in sleep architecture. Since first study of sleep and pregnancy published
      in 1968 there have been very few publications addressing maternal sleep
      postpartum. Most studies which have focussed on quality of maternal sleep in the
      first 6-months postpartum period describe the relationships between poor maternal
      sleep and postpartum depression and other mental health outcomes. What the
      results of this study add: We explored sleep patterns and reasons for wakefulness
      of first-time mothers immediately following delivery while they remained in the
      hospital environment. We found that environmental factors such as background
      noise, shared rooms, type of delivery, feeding and worrying about the neonate did
      not influence the total sleep time, however, the main outcome of our study is
      that breastfeeding promotes maternal sleep. What the implications are of these
      findings for clinical practice and/or further research: We believe that this
      study would be of interest to many obstetricians, general practitioners, nurses
      and midwives as well as to the general public. Appropriate counselling of
      patients early in postnatal period can improve their sleep patterns and reduce
      the risk of depression and other abnormal physical, psychological and social
      outcomes.

PMID- 29022406
TI  - Our experience with Syrian refugee patients at the child and adolescent
      psychiatry clinic in Gaziantep, Turkey.
AB  - Reporting from Turkey's frontier with the civil war in Syria, we examined the
      demographic characteristics, psychiatric diagnoses and treatments for the Syrian
      refugee patients who have presented to Gaziantep University, Child and Adolescent
      Psychiatry Clinic through 2016 and the first half of 2017 retrospectively, having
      aimed to understand the special characteristics and needs of this novel patient
      group. Within a year and a half, we evaluated 51 children and adolescents and 25
      (51%) had come from refugee camps, where primary healthcare services are
      available. Twenty-eight patients (54.9%) had special educational needs. Among our
      patients, there were only 15 (29.4%) girls. After our experience with refugee
      patients, we conclude that the role of primary healthcare services in reaching
      psychiatric treatment should be investigated for child refugees that special
      educational needs of Syrian refugees in Turkey needs urgent attention and that
      more research is needed to establish whether gender may be a factor in negligence
      of internalising symptoms by refugee families.

PMID- 29022407
TI  - The potential of KDM3A as a therapeutic target in Ewing Sarcoma and other
      cancers.

PMID- 29022408
TI  - Screening of colorectal cancer: present and future.
AB  - INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer in males
      and second in females, and the fourth most common cause of cancer death
      worldwide. Currently, about 60-70% of diagnosed cases in symptomatic patients are
      detected at an advanced stage of disease. Earlier stage detection through the use
      of screening strategies would allow for better outcomes in terms of reducing the
      disease burden. Areas covered: The aim of this paper is to review the current
      published evidence from literature which assesses the performance and
      effectiveness of different screening tests for the early detection of CRC. Expert
      commentary: Adequate screening strategies can reduce CRC incidence and mortality.
      In the last few decades, several tests have been proposed for CRC screening. To
      date, there is still insufficient evidence to identify which approach is
      definitively superior, and no screening strategy for CRC can therefore be defined
      as universally ideal. The best strategy would be the one that can be economically
      viable and to which the patient can adhere best to over time. The latest
      guidelines suggest colonoscopy every 10 years or annual fecal immuno-chemical
      test (FIT) for people with normal risk, while for individuals with high risk or
      hereditary syndromes specific recommendations are provided.

PMID- 29022409
TI  - Bilateral transient osteoporosis of the hip in pregnancy.

PMID- 29022410
TI  - Use of Amplatzer occluders for treatment of aorto-pulmonary fistulas - case and
      review of the literature.
AB  - INTRODUCTION: the use of amplatzer occluder family in daily clinical practice has
      already overcome on-label indications, with growing clinical experience and the
      technological evolution of devices. Areas covered: We present the case of a
      patient with a very rare complication following proximal aortic surgery treated
      using a unique strategy. A huge pseudoaneurysm around an ascending aortic
      prosthesis ruptured into the right pulmonary artery. A hybrid treatment strategy
      consisting of percutaneous closure of the fistula followed by cardiosurgery was
      chosen due to the patient's poor haemodynamic condition. We also review current
      clinical experience of endovascular treatment of aortopulmonary fistulas by
      searching case reports in PubMed. Expert commentary: Closure of the APF using an
      Amplatzer occluder via the antegrade venous approach is feasible, and may improve
      the haemodynamic conditions and decrease the risk of subsequent cardiac surgery.

PMID- 29022411
TI  - Comparison of acoustic therapies for tinnitus suppression: a preliminary trial.
AB  - OBJECTIVE: This study obtained preliminary data using two types of sound therapy
      to suppress tinnitus and/or reduce its functional effects: (1) Notched noise
      (1000-12,000 Hz notched within a 1-octave range centred around the tinnitus pitch
      match [PM] frequency); and (2) Matched noise (1-octave wide band of noise centred
      around the PM frequency). A third (Placebo) group listened to low frequency noise
      (250-700 Hz). DESIGN: Participants with bothersome tinnitus were randomised into
      one of the three groups and instructed to listen to the acoustic stimulus for 6
      hours a day for 2 weeks. Stimuli were delivered using an iPod Nano, and tinnitus
      counselling was not performed. Outcome measures were recorded at the 0, 2 and 4
      week study visits. STUDY SAMPLE: Thirty participants with constant and bothersome
      tinnitus were recruited and randomised. RESULTS: All groups showed, on average,
      overall improvement, both immediately post-treatment and 2 weeks following
      treatment. Outcomes varied between groups on the different measures and at the
      two outcome points. CONCLUSION: This study showed improvement for all of the
      groups, lending support to the premise that any type of sound stimulation is
      beneficial for relieving effects of tinnitus. These results may serve as a
      preliminary evidence for a larger study.

PMID- 29022412
TI  - Photo-sharing social media for eHealth: analysing perceived message effectiveness
      of sexual health information on Instagram.
AB  - Health professionals increasingly use social media to communicate health
      information, but it is unknown how visual message presentation on these platforms
      affects message reception. This study used an experiment to analyse how young
      adults (n = 839) perceive sexual health messages on Instagram. Participants were
      exposed to one of four conditions based on visual message presentation. Messages
      with embedded health content had the highest perceived message effectiveness
      ratings. Additionally, message sensation value, attitudes and systematic
      information processing were significant predictors of perceived message
      effectiveness. Implications for visual message design for electronic health are
      discussed.

PMID- 29022413
TI  - Moderate O3/O2 therapy enhances enzymatic and non-enzymatic antioxidant in brain
      and cochlear that protects noise-induced hearing loss.
AB  - Mitochondrial damage and oxidative stress are known to contribute to the
      pathogenesis of noise-induced hearing loss (NIHL). In this study, we examined the
      protective effect of O2/O3 mixture (ozone/oxygen) therapy against mitochondrial
      induced damage and oxidative stress by noise exposure in rat brain and cochlear.
      For this purpose, rats were divided into four groups: 1 - control group; 2 -
      noise-exposed group (100 dB); 3 - noise + O2/O3, and 4 - O2/O3 (30 ug/ml). After
      14 d, animals were anesthetised. Rat brain and cochlear tissue were removed for
      evaluation of the histopathological damages, oxidative stress, and mitochondrial
      dysfunction in both tissues. Our findings indicated that noise caused
      pathological damage, oxidative stress, and mitochondrial dysfunction in rat brain
      and cochlear. Also, daily administration of an O2/O3 therapy (30 ug/ml
      intravenous) efficiently increased enzymatic and non-enzymatic antioxidant in
      brain and cochlear that this action led to inhibition of pathological damages,
      oxidative stress, reactive oxygen species formation, mitochondrial membrane
      potential (MMP) collapse, mitochondrial swelling, and cytochrome c release
      resulting from noise. These findings suggest that the moderate O2/O3 therapy
      enhances the capacity of enzymatic and non-enzymatic antioxidant in brain and
      cochlear that protects against NIHL.

PMID- 29022414
TI  - Iatrogenic Breast Infarct Following Coronary Artery Bypass Graft Surgery With
      Harvesting of Left Internal Mammary Artery.

PMID- 29022415
TI  - Doctrine of equivalents in Japan - criteria of special conditions and estoppel:
      final conclusion.

PMID- 29022416
TI  - Effects of 2-amino-9H-pyrido[2,3-b]indole (AalphaC) metabolic bio-activation on
      oxidative DNA damage in human hepatoma G2 (HepG2) cells.
AB  - 2-Amino-9H-pyrido[2,3-b]indole (AalphaC), which is a hazardous compound present
      in cigarette smoke, has been listed as probable human carcinogens (Group 2B). The
      carcinogenicity and genotoxicity of AalphaC were activated by the process of
      metabolic bio-activation. Whereas, few studies about genotoxicity induced by
      AalphaC have been reported. In this study, we took HepG2 cells as the model to
      investigate the relationship between oxidative DNA damage induced by AalphaC and
      metabolic bio-activation of AalphaC, which is of importance to unveil the
      mechanism of AalphaC genotoxicity. Firstly, the HepG2 cells were treated with 10
      and 20 MUg/mL AalphaC, respectively. Then different concentrations of protein
      ranging from 0 to 1 mg/mL in S9 mixture solution were utilized to make cells have
      different capacities for metabolic activation. Intracellular AalphaC hydroxylated
      metabolites and 8-OHdG were estimated by using ultra-performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS). The results showed that, at
      the same concentration of AalphaC, with the increment of concentration of protein
      in S9 mixture solution, the levels of hydroxylated metabolites and 8-OHdG/106dG
      increased. And at the same concentration of protein in S9 mixture solution, with
      the increment of concentration of AalphaC, the levels of hydroxylated metabolites
      and 8-OHdG/106dG increased. The hydroxylated metabolites and 8-OHdG were
      positively related by correlation analysis. In addition, the correlation
      coefficients of N-OH-AalphaC and 8-OHdG were maximum (R2 = 0.73 and 0.66). Taken
      together, these results indicated that the metabolic bio-activation of AalphaC
      might result in oxidative DNA damage.

PMID- 29022417
TI  - Prevalence of pain medication prescriptions in France, Germany, and the UK - a
      cross-sectional study including 4,270,142 patients.
AB  - OBJECTIVES: The goal of the present study was to analyze the prevalence of pain
      medication prescriptions in general practices in France, Germany, and the UK.
      METHODS: This study included all patients aged >=18 years followed in 2016 in
      general practitioner practices in France, Germany and the UK. The primary outcome
      was the prevalence of patients receiving prescriptions for pain medications in
      France, Germany, and the UK in 2016. The following drugs were included in the
      analysis: anti-inflammatory and antirheumatic products, non-steroids and
      analgesics including opioids, antimigraine preparations, and other analgesics and
      antipyretics. Demographic variables included age and gender. RESULTS: This study
      included 4,270,142 patients. The prevalences of pain medication prescriptions
      were 57.3% in France, 29.6% in Germany, and 21.7% in the UK. Although this
      prevalence generally remained consistent between age groups in France (54.3%
      60.3%), it increased with age in Germany (18-30 years: 23.8%; >70 years: 35.8%)
      and in the UK (18-30 years: 9.3%; >70 years: 43.8%). Finally, the prevalence of
      pain medication prescriptions was higher in women than in men in all three
      countries. Paracetamol was prescribed to 82.3% and 60.1% of patients receiving
      pain medication in France and the UK, respectively, whereas ibuprofen was
      prescribed to 46.5% of individuals in Germany. CONCLUSIONS: The prevalence of
      pain medication prescriptions was higher in France than in Germany and the UK.
      Further research is needed to gain a better understanding of the differences in
      the prescription patterns between these three European countries.

PMID- 29022418
TI  - Patent protection: why the first filing needs to be right and how to achieve
      this.
AB  - Patent rights are crucial value drivers for individuals and technology companies,
      large or small. This article presents the selection of best practice pointers
      under the law of the European Patent Office on how to get the most out of patent
      applications, especially the 'first filing' that establishes a priority date for
      and sets the framework for future patent rights.

PMID- 29022419
TI  - Speech-evoked auditory brainstem response with ipsilateral noise in adults with
      unilateral hearing loss.
AB  - INTRODUCTION: Subjects with unilateral hearing loss (UHL) report difficulties in
      speech understanding in noise. Speech-evoked auditory brainstem response (S-ABR)
      provides cues for temporal and spectral encoding of speech in the brainstem. S
      ABR recording in noise increases its sensitivity in evaluating the auditory
      processing and related disorders. OBJECTIVES: Study speech encoding at the level
      of brainstem when the auditory system relies on one ear and to study the effect
      of noise on this encoding. SUBJECTS AND METHOD: This study included two groups:
      control group consisted of 15 adults with normal hearing sensitivity and study
      group consisted of 30 adults with UHL. The study group was further subdivided
      into two subgroups: study subgroup A (SG A) consisted of 15 adults with right
      functioning ears and study subgroup B (SG B) consisted of 15 adults with left
      functioning ears. S-ABR in quiet and with ipsilateral noise was recorded in both
      the groups using complex ABR advanced auditory research module. RESULTS: In UHL,
      there was a statistically significant delay in the S-ABR onset and offset in
      noise compared to quiet. Moreover, quiet-noise (+5 SNR) correlation was
      significantly low compared to NH. Furthermore, pitch representation (F0
      amplitude) was significantly degraded with noise. In addition, there was a
      statistically significant noise-induced phase shift in the transition region of
      speech syllable in these subjects. CONCLUSION: In monaural processing, pitch
      representation (F0 amplitude) and cross-phaseogram were the main affected
      domains. Speech phonemes of transient origin can be confused in subjects with
      UHL.

PMID- 29022420
TI  - Recommendations on the use of ruxolitinib for the treatment of myelofibrosis.
AB  - OBJECTIVES: Myelofibrosis (MF) is a severe disease, with decreased life
      expectancy and heavy symptom burden. Ruxolitinib is the only approved
      pharmacotherapy for the treatment of MF patients. In Belgium, ruxolitinib is only
      reimbursed for MF patients with splenomegaly for whom the disease is categorized
      as intermediate-2 or high risk. The improvement of symptoms without spleen volume
      reduction is not considered sufficient to continue treatment. The aim of this
      manuscript is to provide guidance for the safe and effective administration of
      ruxolitinib, considering the particularities of the Belgian reimbursement
      criteria. METHODS: Our recommendations are based on a consensus reached during
      two meetings, where available data and observations derived from clinical
      experience were discussed. RESULTS AND DISCUSSION: We recommend changing the
      current Belgian reimbursement conditions to include the evaluation of disease
      related symptoms along with splenomegaly to decide whether ruxolitinib treatment
      should be continued or not. Indeed, the decrease in disease-related symptoms
      seems to be an equally important parameter as the decrease in splenic volume in
      the evaluation of the response to ruxolitinib. We also advocate for the treatment
      with ruxolitinib of MF patients in lower-risk categories with severe disease
      related symptoms, as this drug could greatly improve their quality of life.
      Optimization of the ruxolitinib dose is recommended to avoid an unnecessary
      decrease in platelet count or hemoglobin that may jeopardize treatment
      continuation. CONCLUSION: With the aim to optimize the treatment of MF patients,
      the Belgian regulation for ruxolitinib should be revised in terms of
      reimbursement criteria, dose titration, stopping rules, and patient follow-up.

PMID- 29022421
TI  - Characterization of two distinct lipomas: a comparative analysis from surgical
      perspective.
AB  - BACKGROUND: Lipomas are common benign soft tissue tumors that are well
      circumscribed and encapsulated. However, adipose masses that are not demarcated
      from the surrounding fat are often encountered. Two distinct types of lipomas
      were analyzed from surgical perspective. METHODS: Thirty patients were enrolled
      after lipoma excision and diagnosed with either encapsulated (n = 20) or non
      encapsulated lipoma (n = 10). Comparison of clinical variables, histologic
      analyses and characterization of the lipoma adipose-derived stem cells (ASCs)
      between the two lipomas were performed. RESULTS: Non-encapsulated lipomas were
      associated with older age at operation, larger tumor and increased seroma
      formation. The density of lymphatic vessels and gene expressions related to
      lymphatic vessel, inflammation and proliferation were increased in non
      encapsulated lipoma. ASCs of non-encapsulated lipoma showed enhanced
      proliferation when cultured with serum. CONCLUSIONS: Non-encapsulated lipomas and
      their ASCs showed distinct lymphatic histology and cellular response. These
      findings elucidated the pathogenesis and pathophysiology of lipomas.

PMID- 29022422
TI  - Investigating cognitive ability and self-reported driving performance of post
      stroke adults in a driving simulator.
AB  - Background Safe driving is a complex activity that requires calibration. This
      means the driver can accurately assess the level of task demand required for task
      completion and can accurately evaluate their driving capability. There is much
      debate on the calibration ability of post-stroke drivers. Objectives The aim of
      this study was to assess the cognition, self-rated performance, and estimation of
      task demand in a driving simulator with post-stroke drivers and controls. Methods
      A between-groups study design was employed, which included a post-stroke driver
      group and a group of similarly aged older control drivers. Both groups were
      observed driving in two simulator-based driving scenarios and asked to complete
      the NASA Task Load Index (TLX) to assess their perceived task demand and self
      rate their driving performance. Participants also completed a battery of
      psychometric tasks to assess attention and executive function, which was used to
      determine whether post-stroke cognitive impairment impacted on calibration.
      Results There was no difference in the amount of perceived task demand required
      to complete the driving task. Despite impairments in cognition, the post-stroke
      drivers were not more likely to over-estimate their driving abilities than
      controls. On average, the post-stroke drivers self-rated themselves more poorly
      than the controls and this rating was related to cognitive ability. Conclusion
      This study suggests that post-stroke drivers may be aware of their deficits and
      adjust their driving behavior. Furthermore, using self-performance measures
      alongside a driving simulator and cognitive assessments may provide complementary
      fitness-to-drive assessments, as well as rehabilitation tools during post-stroke
      recovery.

PMID- 29022423
TI  - Combination antiplatelet treatment in coronary artery disease patients: A
      necessary evil or an overzealous practice?
AB  - In seeking to improve care in coronary artery disease patients, further platelet
      inhibition has been occasionally applied beyond that provided by aspirin and a
      P2Y12 receptor antagonist. This review aims to offer insights about the
      rationale, the efficacy and safety of combination antiplatelet therapy, involving
      three or more agents. Overall, the use of glycoprotein (GP) IIb/IIIa inhibitors
      did not significantly modify the treatment effect of different antiplatelet
      strategies, including double vs standard clopidogrel, prasugrel vs clopidogrel,
      ticagrelor vs clopidogrel, cangrelor vs clopidogrel, and vorapaxar vs placebo.
      With the caveat that the use of GP IIb/IIIa inhibitor was not randomized, adding
      such an agent to aspirin and a P2Y12 receptor antagonist appears to carry a
      significantly increased bleeding potential. Moreover, adding vorapaxar to aspirin
      and clopidogrel-treated patients is associated with more bleeding events, while
      the bleeding potential is further exacerbated in cases of quadruplicate
      antiplatelet treatment including aspirin, clopidogrel, vorapaxar, and a GP
      IIb/IIIa inhibitor. In ST-segment elevation, myocardial infarction patients'
      administration of an intravenous antiplatelet agent (GP IIb/IIIa inhibitor or
      cangrelor), in addition to aspirin and a P2Y12 receptor antagonist, efficiently
      bridges the pharmacodynamic gap of oral agents. Cilostazol on top of aspirin and
      clopidogrel appears to be safe, although of questionable clinical benefit. In
      conclusion, combination antiplatelet therapy should be reserved only for selected
      cases and following thoughtful consideration of the associated risk/benefit
      ratio.

PMID- 29022424
TI  - Cytogenetic analysis of patients with primary amenorrhea in Eastern India.
AB  - Amenorrhea is the absence of menstruation in women of reproductive age. Previous
      reports suggest that chromosomal abnormality is the second most common cause of
      amenorrhoea. Early referral for cytogenetic evaluation is recommended for the
      identification of underlying chromosomal aberrations in amenorrhoea patients.
      This was an observational study which was conducted in Vivekananda Institute of
      Medical sciences, Kolkata, during January 2013-December 2015. This study aims to
      estimate the frequency and types of chromosomal abnormalities in primary
      amenorrhoea (PA) patients in Eastern India and correlate their hormonal profile
      with chromosomal reports. Clinical features of 150 patients were recorded with
      clinical expertise. Peripheral venous blood was taken following informed consent,
      followed by karyotyping for chromosomal analysis. Results revealed 76.1% of PA
      with normal female karyotype (46, XX) and 23.9% with different abnormal
      karyotypes. Among the abnormal karyotype constituents, 50% numerical
      abnormalities, most frequent being Turner syndrome, pure (n = 12, 8%) and mosaic
      (n = 5, 3.3%). Three cases (2%) showed male (XY) karyotype. The other cases
      showed X structural abnormalities. This study emphasises the need for cytogenetic
      analysis as integral part of the diagnostic protocol in case of PA for precise
      identification of chromosomal abnormalities and for appropriate management and
      counselling of these patients.

PMID- 29022425
TI  - Biologics in pediatric psoriasis - efficacy and safety.
AB  - INTRODUCTION: Childhood psoriasis is a special situation that is a management
      challenge for the treating dermatologist. As is the situation with traditional
      systemic agents, which are commonly used in managing severe psoriasis in
      children, the biologics are being increasingly used in the recalcitrant disease
      despite limited data on long term safety. Areas covered: We performed an
      extensive literature search to collect evidence-based data on the use of
      biologics in pediatric psoriasis. The relevant literature published from 2000 to
      September 2017 was obtained from PubMed, using the MeSH words 'biologics',
      'biologic response modifiers' and 'treatment of pediatric/childhood psoriasis'.
      All clinical trials, randomized double-blind or single-blind controlled trials,
      open-label studies, retrospective studies, reviews, case reports and letters
      concerning the use of biologics in pediatric psoriasis were screened. Articles
      covering the use of biologics in pediatric psoriasis were screened and reference
      lists in the selected articles were scrutinized to identify other relevant
      articles that had not been found in the initial search. Articles without relevant
      information about biologics in general (e.g. its mechanism of action,
      pharmacokinetics and adverse effects) and its use in psoriasis in particular were
      excluded. We screened 427 articles and finally selected 41 relevant articles.
      Expert opinion: The available literature on the use of biologics such as anti
      tumor necrosis factor (TNF)-alpha agents, and anti-IL-12/23 agents like
      ustekinumab suggests that these are effective and safe in managing severe
      pediatric psoriasis although there is an urgent need to generate more safety
      data. Dermatologists must be careful about the potential adverse effects of the
      biologics before administering them to children with psoriasis. It is likely that
      with rapidly evolving scenario of biologics in psoriasis, these will prove to be
      very useful molecules particularly in managing severe and recalcitrant psoriasis
      in pediatric age group.

PMID- 29022426
TI  - Ignorance is bliss: women's knowledge regarding age-related pregnancy risks.
AB  - Pregnancy risks rise with age and the average age of first time mothers is
      rising. This study aimed to assess women's actual knowledge and their perceived
      knowledge of pregnancy complications relating to advanced maternal age. A cross
      sectional survey was administered to primiparous women measuring demographics,
      knowledge of age-related pregnancy risks, previous counselling and health
      literacy. Of the 218 women surveyed, the mean knowledge score was not
      significantly different for women <35 years of age compared to women >=35 years
      of age (p = .09). Although there was no difference in knowledge between the two
      groups, women >=35 years of age perceived themselves to be more knowledgeable
      than those under 35 (p < .01). The majority of women (67%) wanted further
      counselling on this topic and indicated a preference for their doctor to counsel
      them (76%). Women require counselling informing them of their increased risk of
      complications if they begin childbearing at older ages. Impact statement What is
      already known on this subject: The average age of first time mothers is rising
      worldwide. Pregnancy risks rise with age, especially in first time mothers.
      Previous studies have shown that knowledge of age-related pregnancy risks
      correlate with educational level and health literacy. What the results of this
      study add: This study supports those findings and also demonstrates that
      perceived knowledge does not correlate with measured knowledge of age-related
      pregnancy risks. Women >=35 years of age (higher-risk women) are no more
      knowledgeable than their younger counterparts though they perceive themselves to
      be better informed. Greater education regarding these risks may allow women to
      mitigate some of these risks through lifestyle and diet alteration and will
      prepare women for what to expect if these risks and complications occur. The
      majority of women in this study seek pregnancy information on the internet, but
      desire further counselling from their doctors regarding age-related pregnancy
      risks. What the implications are of these findings for clinical practice and/or
      further research: Given these results, physicians must consider making greater
      efforts to counsel women about pregnancy risks in advanced maternal age and
      tailor these conversations to suit the educational level and health literacy of
      each individual patient.

PMID- 29022429
TI  - TCN Vol. 4, No. 1: Overview: The editors.

PMID- 29022428
TI  - Editorial board page for "The Clinical Neuropsychologist", Volume 4, Number 1.
AB  - This is a scanned image of the original Editorial Board page(s) for this issue.

PMID- 29022427
TI  - Confirming the timing of phase-based costing in oncology studies: a case example
      in advanced melanoma.
AB  - AIMS: The utilization of healthcare services and costs among patients with cancer
      is often estimated by the phase of care: initial, interim, or terminal. Although
      their durations are often set arbitrarily, we sought to establish data-driven
      phases of care using joinpoint regression in an advanced melanoma population as a
      case example. METHODS: A retrospective claims database study was conducted to
      assess the costs of advanced melanoma from distant metastasis diagnosis to death
      during January 2010-September 2014. Joinpoint regression analysis was applied to
      identify the best-fitting points, where statistically significant changes in the
      trend of average monthly costs occurred. To identify the initial phase, average
      monthly costs were modeled from metastasis diagnosis to death; and were modeled
      backward from death to metastasis diagnosis for the terminal phase. Points of
      monthly cost trend inflection denoted ending and starting points. The months
      between represented the interim phase. RESULTS: A total of 1,671 patients with
      advanced melanoma who died met the eligibility criteria. Initial phase was
      identified as the 5-month period starting with diagnosis of metastasis, after
      which there was a sharp, significant decline in monthly cost trend (monthly
      percent change [MPC] = -13.0%; 95% CI = -16.9% to -8.8%). Terminal phase was
      defined as the 5-month period before death (MPC = -14.0%; 95% CI = -17.6% to 
      10.2%). LIMITATIONS: The claims-based algorithm may under-estimate patients due
      to misclassifications, and may over-estimate terminal phase costs because
      hospital and emergency visits were used as a death proxy. Also, recently approved
      therapies were not included, which may under-estimate advanced melanoma costs.
      CONCLUSIONS: In this advanced melanoma population, optimal duration of the
      initial and terminal phases of care was 5 months immediately after diagnosis of
      metastasis and before death, respectively. Joinpoint regression can be used to
      provide data-supported phase of cancer care durations, but should be combined
      with clinical judgement.

PMID- 29022430
TI  - Contributions of Kurt Goldstein to neuropsychology.
AB  - Kurt Goldstein was a pioneer of neuropsychology; his long career bridged a time
      span between nineteenth century European behavioral neurology and the modern era
      of clinical neuropsychology. In this retrospective analysis of his major
      contributions, it is suggested that many of his previously ignored or rejected
      ideas have gained wide acceptance in their modern versions. Illustrations of this
      suggestion are offered in the areas of conceptualization of symptom formation,
      frontal lobe function, the abstract attitude, aphasia, schizophrenia,
      rehabilitation, and neuropsychological assessment.

PMID- 29022432
TI  - Effects of language disturbances on premorbid estimates of IQ in mild dementia.
AB  - Two methods were used to estimate premorbid IQ in a sample of 68 patients with
      mild dementia: (1) the National Adult Reading Test (NART), a present ability
      measure, and (2) an age, sex, race, education and occupation regression formula,
      a demographically based estimate (DIQ). The dementia sample consisted of probable
      Alzheimer's disease, multi-infarct dementia and a mixture of the two. The sample
      was divided into three levels of language disturbances (no language disturbance,
      naming or fluency disturbance, or both naming and fluency disturbance) based upon
      performance on the Visual Naming test and the Controlled Oral Word Association
      test. The NART IQ estimates in patients with one or more language disturbances
      were significantly lower than those in patients without language disturbances
      despite equivalent DIQ and Mini-Mental Status exam performance. The results
      suggest that the applicability of the NART to dementia patients with prominent
      language disturbances is limited.

PMID- 29022433
TI  - The MMPI and neurologic dysfunction: Profile configuration and analysis.
AB  - This study examined the application of the Minnesota Multiphasic Personality
      Inventory (MMPI) to the assessment of personality and emotional status in
      neurologic patients. Eighteen specialists in the clinical neurosciences examined
      the standard MMPI and indicated those items they felt were potentially tapping
      valid manifestations of neurologic damage or dysfunction. Forty-four items,
      loading primarily on the Hs, Hy, and Sc scales, were identified. These items were
      then deleted from the standard MMPI protocols of a heterogeneous group of 115
      verified neurologic patients and the protocols rescored in the usual fashion.
      Corresponding high-points between the original MMPI and the modified version
      occurred in 46% of the cases. Comparable two-point code types occurred in only
      29% of the cases. Taking into account the neurologic content of the MMPI can thus
      considerably alter the MMPI profile of a neurologic patient. Caution should thus
      be exercised with regard to the application and literal interpretation of the
      MMPI in neurologic cases.

PMID- 29022434
TI  - A consideration of the comparability of the WAIS and WAIS-R.
AB  - The WAIS-R continues to be used on a widespread basis as a substitute for the
      WAIS in neuropsychological assessment, in spite of cautions that have been
      published (Bornstein, 1987). Although differences in results obtained with the
      two instruments have been reported, a feeling seems to exist that content
      differences between the two tests are minimal. This paper presents a detailed
      comparison of the subtests and reports that substantial differences in content
      are often present. Finally, our literature search failed to reveal a single study
      in which the WAIS-R has been shown to be sensitive to cerebral damage through
      controlled comparisons of brain-damaged and control groups. Sufficient evidence
      is not yet available to justify substitution of the WAIS-R for the WAIS in
      neuropsychological assessment.

PMID- 29022436
TI  - Use of the national adult reading test to estimate premorbid iq in dementia.
AB  - Two methods for estimating premorbid IQ were employed in a sample of 199 dementia
      patients and 26 control subjects: (1) the National Adult Reading Test (NART), a
      present ability measure, and (2) an age, sex, race, education and occupation
      regression formula-a demographically based estimate. The dementia sample
      consisted of probable Alzheimer's disease, multi-inf arct dementia and a mixture
      of the two. Controls consisted of the spouses of the patient sample. The patient
      sample was divided into three levels of dementia severity equated for age and
      level of education. The NART estimates in the mild and moderate/severe dementia
      groups differed significantly from those for the very mildly demented patients
      and controls. The results suggest that the applicability of the NART in
      estimating premorbid IQ in dementia may be limited.

PMID- 29022437
TI  - Malingering following Minor head trauma.
AB  - The possibility of malingering should be considered whenever an opportunity for
      financial gain exists or when the subjective complaints outweigh the objective
      findings. Minor-head-injury patients often meet one or both of these criteria.
      Four cases of probable malingering and one case of possible malingering after
      minor head injury are discussed. Observations of untruthfulness, test
      abnormalities more severe than predicted by knowledge of the injury, bizarre
      results on Face-Hand (Double Simultaneous Stimulation) testing, and especially
      forced-choice testing of memory complaints provided useful diagnostic data in
      these cases. Performance on a forced-choice technique that is significantly worse
      than chance is presumed to result from the deliberate production of wrong
      answers. An improved method of forced-choice testing based on work by Hiscock and
      Hiscock (in press) is presented.

PMID- 29022438
TI  - Interrater agreement on the Benton visual retention test.
AB  - To address overlapping needs in clinical neuropsychology and epidemiology of the
      elderly, we report an in-depth analysis of interrater scoring for a test commonly
      used to assess visual memory in older persons. Benton Visual Retention Test
      protocols (Form C, Administration A) from 277 community-dwelling male
      participants (M = 65.2 years) in two ongoing cardiovascular epidemiologic studies
      were scored independently by two trained raters. Interrater reliabilities,
      calculated as intraclass correlations, were .963 and .974 for total number of
      correct reproductions and total number of errors, respectively. Interrater
      agreements on categorical determinations of the presence or absence of 6 error
      codes on 10 separate designs were evaluated using kappa measures of agreement.
      Kappa values for each of the 10 designs ranged between .780 and .930. Kappa
      values for each of the error codes ranged from a high of .976 for omissions to a
      moderate .737 for size errors. Kappa values by error code type within each of the
      10 designs revealed particular problem areas for misplacements on design 9 and
      size errors on design 10 (kappa being as low as .440 and .480 respectively).
      Suggestions for improving the accuracy of scoring are presented.

PMID- 29022439
TI  - Performance measures of 16- to 86-year-old males and females on the auditory
      verbal learning test.
AB  - This study reports Auditory Verbal Learning Test (AVLT) data for 153 adults in
      age groups spanning seven decades, with approximately equal numbers of males and
      females and matched for intelligence, education, and occupation. Overall
      performance deteriorated with increased age, females performing better than
      males. Older subjects recalled fewer words, were more susceptible to information
      overload during input, showed diminished retrieval efficiency, and had a decline
      in memory for the source of items. In contrast, rate of learning, forgetting over
      20-min, monitoring of recall, and interference effects remained stable across the
      age range.

PMID- 29022441
TI  - TCN Vol. 6, No. 2: Overview: The editors.

PMID- 29022440
TI  - Some gnomes worth knowing.
AB  - Clinical neuropsychology varies greatly in its level of development even in
      countries where it has reached a high degree of sophistication in some centres.
      Benton (1987) pointed to the continuation of vague terminology among many
      psychologists in this area, even some who consider they are practising
      neuropsychology. This vagueness is often accompanied by a primitive
      conceptualization of the organization of the brain for the purpose of subserving
      higher functions and "an uncritical interpretation of test findings" and "the
      drawing of unwarranted conclusions" from test results about the state of the
      brain. After a brief consideration of the network concept of cerebral
      functioning, some examples of errors and difficulties in test interpretation are
      given in the form of gnomes or aphorisms from prominent clinicians to demonstrate
      the need for improvement of the education of all psychologists who are likely to
      be faced with essentially neuropsychological problems.

PMID- 29022443
TI  - A Review of reference group data from normal children for the halstead-reitan
      neuropsychological test battery for older children.
AB  - This article reviews data gathered from samples of normal children who were
      assessed with the Halstead-Reitan Neuropsychological Test Battery for Older
      Children (HRB-OC), ages 9-14 years. Graphic comparisons by age group indicate
      clear developmental trends for all measures except TPT-memory, TPT-localization,
      and Seashore Rhythm Test. Methods used to analyze variability of the measures
      suggested that the following may be unreliable: Tactual Performance Test, all
      timed measures, memory and localization tasks; Trail Making Test, Part B among
      younger children; Speech-Sounds Perception Test; and Seashore Rhythm Test. These
      results are consistent with published reliability data from a study of referred
      children. The HRB-OC remains a powerful tool when combined with multiple methods
      of assessment and clinical expertise.

PMID- 29022444
TI  - Free-recall, cued-recall and recognition procedures with three verbal memory
      tests: Normative data from age 20 to 79.
AB  - New versions of three verbal learning tests (paragraph learning, list learning,
      and word-pair learning) were normed on 420 subjects, aged 20 to 79. These tasks
      used multiple acquisition trials, employed a delayed retention trial,
      incorporated the Buschke Selective Reminding procedure and utilized a continuum
      of free-recall, cued-recall, and recognition tasks. Norms are presented for six,
      10-year age groups equated for intellectual level and gender. Normative groups
      also were screened for depression, dementia, and psychiatric illness. Results
      showed that all three tasks were highly reliable, demonstrated promising
      construct validity, and appeared to be measuring the same underlying cognitive
      function. Basic interpretative stategies for use with clinical data are proposed.

PMID- 29022445
TI  - Editorial board page for "The Clinical Neuropsychologist", Volume 6, Number 2.
AB  - This is a scanned image of the original Editorial Board page(s) for this issue.

PMID- 29022446
TI  - Analysis of learning and rate of forgetting in age-associated memory differences.
AB  - This study used a visual free-recall paradigm to examine rate of forgetting in a
      sample of 255 normal adults (age range 18-91 years). Subjects were administered
      the Visual Reproduction Subtest (VR) from Form I of the Wechsler Memory Scale,
      along with a 30-min delayed-recall procedure. Results revealed that older adults
      performed below levels obtained by younger ones on both phases of the VR.
      However, analysis revealed no differences among age groups in rate of forgetting.
      Lower scores for older subjects on the delayed-recall task appeared to reflect
      differences in initial learning, not an accelerated rate of forgetting. Normative
      data for rate of forgetting were provided for adults in all age groups.

PMID- 29022447
TI  - Memory failure in binswanger's disease and alzheimer's disease.
AB  - The heterogeneity within vascular dementia has made neuropsychological research
      in this area difficult to interpret. We studied a subtype of vascular dementia,
      Binswanger's disease (BD), diagnosed according to recently specified clinical and
      radiological criteria. Measures of episodic and semantic memory were administered
      to BD patients, patients with Alzheimer's disease (AD) comparable to the BD
      sample in dementia severity, age, and education, and normal controls. Episodic
      memory was more defective in AD than in BD; these patient groups were equally
      impaired on measures of semantic memory. The findings suggest that assessment of
      episodic memory may be useful in differentiating AD from BD.

PMID- 29022448
TI  - Confrontation naming in normally developing children: Word-retrieval or word
      knowledge?
AB  - This study presents normative data on the Boston Naming Test (BNT) for 382
      normally developing children as a framework for evaluating what the BNT measures:
      word-retrieval or vocabulary. A Revised Children's BNT is proposed based on item
      analyses of the 212 boys' responses. Some BNT items were part of the boys'
      vocabulary at all ages, some entered their working vocabulary with age, some were
      affected by age and experience, and others were not part of the boys' working
      vocabulary at any age. Error analyses revealed that the pattern of errors in the
      boys differed from that of adult aphasics. Two error types, semantic and
      circumlocution, accounted for 82% of the boys' errors whereas three types
      characterize adult aphasics: semantic, phonemic, and circumlocution. The boys
      made semantic errors most frequently on age-related items; circumlocution errors
      were made on items that were not part of their working vocabulary. Suggestions
      for evaluating aphasic-like errors are presented.

PMID- 29022449
TI  - Interrater reliability in scoring the Wisconsin card sorting test.
AB  - Neuropsychological instruments continue to proliferate the field, while studies
      systematically addressing their accuracy and standardization have lagged behind.
      This paper examines the standard scoring criteria on a widely used
      neuropsychological test, the Wisconsin Card Sorting Test (WCST). Specifically,
      the scoring criteria for the perseveration variables are complex and interrater
      reliability had not yet been established. Study 1 revealed excellent interrater
      reliability between three individuals experienced with the WCST who had
      independently learned the scoring procedures. Study 2 demonstrated excellent
      interrater agreement among six novice raters. Some of the novice scorers used
      supplemental scoring instructions that were developed in an attempt to improve
      understanding of the manual. The supplemental scoring instructions reduced
      training time by 41% without affecting the high reliability between the raters.
      This paper also illustrates an appropriate use of generalizability theory, a
      powerful statistical method to examine reliability.

PMID- 29022451
TI  - Evidence for early acquisition of visual organization ability: A developmental
      study.
AB  - This study presents normative data on the Hooper Test of Visual Organization for
      434 normally developing children within the context of adequate confrontation
      naming, as measured by the Boston Naming Test. Age and gender differences were
      observed. Children's capacity to identify common objects from fragmented visual
      information approached borderline adult levels by the age of 6. The boys attained
      adult performance levels by age 12, but the girls did not reach these adult
      levels at any age. This suggests that visual organization ability may have a
      longer developmental course in girls than in boys. A reordered Children's version
      of the Hooper is proposed based on item analyses of the 218 boys' responses.

PMID- 29022450
TI  - Modification of the stroop color word test improves differentiation between
      patients with mild head injury and matched controls.
AB  - Previous studies have indicated that patients with mild head injury have no
      specific deficits in selective attention as assessed with the Stroop Color Word
      Test. It has been reported that patients may be slower to name colors, but that
      they are not disproportionately slower on the subtask with color-word
      interference. The present study examined whether the performance of patients with
      mild head injury (MHI) was worse than that of nonconcussed controls on a modified
      Stroop interference subtask of increased complexity. Patients (n=44) were
      individually matched with controls for age, sex, and education. It was found that
      MHI patients were significantly slower on this modified subtask, whereas there
      was no significant difference between the two groups with the original
      interference subtask. The findings support the hypothesis that the cognitive
      disturbances of patients with mild head injury may be subtle and only
      demonstrable with very sensitive tests.

PMID- 29022452
TI  - Statement regarding the use of nondoctoral personnel for neuropsychological
      assessment.

PMID- 29022453
TI  - The MMPI and closed-head injury.
AB  - This study examined Minnesota Multiphasic Personality Inventory profile
      configuration in matched samples of males (n = 77) and females (n = 25) suffering
      from closed-head injury. For the males, the mean group high-point was the 5c
      scale; the mean group high-point for the females was the D scale. For the males,
      the mean group two-point code was the 8-2 configuration; the mean group two-point
      code for the females was the 2-3 configuration. The males as a group also scored
      significantly higher than the females on the Sc scale. The D scale was the most
      frequently elevated clinical scale and high-point for both groups. The overall
      pattern of findings also suggested a greater predominance of Hs and Hy two-point
      code types for the females. The results are discussed in terms of the need to pay
      critical attention to methodological issues in neuropsychological research and
      practice.

PMID- 29022455
TI  - Editorial board page for "Cognition & Emotion", Volume 6, Number 5.
AB  - This is a scanned image of the original Editorial Board page(s) for this issue.

PMID- 29022456
TI  - Recent Books.
AB  - Fischer, A.H. (1991). Emotion scripts: A study of the social and cognitive facets
      of emotions. Leiden: DSWO Press. ISBN 90-6695-053-6, 220 pp Franks, D.D. &
      McCarthy, E.D. (Eds) (1989). Sociology of emotions: Original essays and research
      papers. Greenwich & London: JAI Press. ISBN 0-89232-759-6, 302 pp, $52.50
      Scheffler, I. (19911. In praise of the cognitive emotions. New York: Routledge.
      ISBN 0-415-90363-7 (hbk)/90364-5 (pbk), 174 pp, L30 (hbk) Forgas, J.P. (Ed.)
      (19911. Emotion and social judgements. Oxford: Pergamon Press. ISBN 0-08-040236-4
      (hbk)/040235-6 (pbk), 301 pp, $76/L38 (hbk), $31.95/L15.95 (pbk) Blechman,
      R.A.(Ed.) (1990). Emotions and the family: For better or for worse. Hillsdale,
      NJ: Lawrence Erlbaum Associates Inc. ISBN 0-8058-0136-7, 241 pp, $36/L26
      Plutchik, R. & Kellerman, H. (Eds) (1990). Emotion: Theory, research and
      experience, Vol. 5: Emotion, psychopathology and psychotherapy. San Diego:
      Academic Press. ISBN 0-12-558705-8, 275 pp, $69/L49.50 Heider, K.G. (Ed.) (1991).
      Landscapes of emotion: Mapping three cultures of emotion in Indonesia. Cambridge
      University Press. ISBN 0-52140151-8, 332 pp, $44.50/L35 Leiddmeijer, L. (1991).
      Emotions: An experimental approach. Tilburg University Press. ISBN 90-361-9634-5,
      235 pp, Df 1.59 Kemper, T.D. (Ed.) (1990). Research agenda in the sociology of
      emotion. New York: State University of New York Press. ISBN 0-7914-0269-X
      (hbk)/0270-3 (pbk), 335 pp, $57.50 (hbk), $18.95 (pbk) Scheff, T.J. (1990).
      Microsociology: discourse, emotion and social structure. University of Chicago
      Press. ISBN 0-226-73666-0, 214 pp, $34.50/L23.95 Averill, J.R. & Nunley, E.P.
      (1992). Voyages of the heart: Living an emotion ally creative life. New York:
      Free Press. ISBN 0-02-9011086, 358 pp, $26.95/ L16.95.

PMID- 29022457
TI  - Training Young Children to Acknowledge Mixed Emotions.
AB  - The failure of children to acknowledge mixed, contradictory emotions is equally
      of developmental and clinical interest. Developmentally, children do not
      ordinarily acknowledge the existence of mixed emotions until late in middle
      childhood. Clinically, the failure to recognise mixed feelings toward others or
      self is a common presenting problem. The question addressed here is, how readily
      can such limitations be corrected in children of different ages. Two studies are
      reported showing that children as young as 6 and 7 years, who initially revealed
      little understanding of mixed feelings, showed more insight after a short
      training session. In Experiment 1. two groups of children were equated for their
      inability to diagnose the mixed feelings of a story character. Subsequently, both
      groups were presented with a second story containing a similar conflictual event,
      but only one group was prompted to consider the character's emotional reaction to
      each component of the conflict. Children in the prompted group were more accurate
      in diagnosing the character's emotional reaction at the end of the story than the
      control group, and they maintained their superiority on a post-test story where
      no prompts were given. Experiment 2 included a similar training procedure. but
      with a more stringent measure of post-test generalisation: Children were asked to
      describe or invent their own examples of emotionally charged conflictual
      situations. Four- and five-year-olds showed little benefit from the training
      session, but six- and seven-year-olds again showed considerable benefit. Taken
      together, the two experiments suggest that young school age children often fail
      to acknowledge mixed feelings because they engage in a cursory appraisal of the
      elements of an emotionally charged situation; highlighting the elements is
      sufficient to improve performance. Preschool children, however, appear to suffer
      from more basic limitations in their ability to integrate the relevant
      information.

PMID- 29022458
TI  - Conjunction in the Language of Emotions.
AB  - Oatley and Johnson-Laird (1987) have proposed a cognitive theory of emotion.
      According to this theory, there are five basic emotions. A major prediction of
      the theory is that it should permit satisfactory definitions for all the emotion
      words in a language, and this was essayed for the English language by Johnson
      Laird and Oatley (1989). The theory proposes that only one emotional state can be
      operative at a time, and therefore words referring to mixed emotions were defined
      by Johnson-Laird and Oatley as disjunctions of basic emotions. Two experiments
      are reported which com pared these disjunctive definitions with conjunctive
      definitions (i.e. definitions inconsistent with the theory). For a number of
      words, conjunctive definitions tended to be preferred. This tendency was
      increased when the disjunctions and conjunctions were made more explicit. This
      finding sug gests that Oatley and Johnson-Laird's theory should be modified so as
      to embrace the conjunction of emotion. That is, it should allow that two or more
      emotions can be exnerienced in parallel.

PMID- 29022459
TI  - Unilateral Facial Contractions Produce Mood Effects on Social Cognitive
      Judgements.
AB  - This study demonstrates that left and right unilateral facial contractions have
      similar effects on the expression of ethnic stereotypes as do negative and
      positive moods induced by more conventional means. Subjects who con tracted the
      left side of their face (negative mood inducer) were more likely to express
      negative stereotypes of ethnic groups than were subjects who contracted the right
      side of their face (positive mood inducer). This parallels previous findings
      obtained using two standard mood inductions: the Veltens mood induction
      procedure; and a musical mood induction procedure. Given that unilateral facial
      contractions manipulate mood without cognitive involvement, this mood induction
      may have advantages over previously used procedures, the effects of which are
      subject to cognitive mediation explanations. In addition, these results suggest
      that, at least for the expression of ethnic stereotypes, mood's influence on
      cognition does not depend on a cognitive component of mood induction.

PMID- 29022460
TI  - The Relative Dominance of Different Facial Expressions of Emotion under
      Conditions of Perceptual Ambiguity.
AB  - Facial expressions of happiness, excitement, surprise, fear, anger, disgust,
      sadness, and calm were presented stereoscopically to create pair wise perceptual
      conflict. Dominance of one expression over another as the most common result, but
      basic emotions (happiness, fear, etc.) failed to dominate non-basic emotions
      (excitement, calm), Instead, extremely pleasant or extremely unpleasant emotions
      dominated less valenced emotions (e.g. surprise). Blends of the presented pairs
      also occurred, mainly when the emotions were adjacent according to a circumplex
      structure of emotion. Blends were most common among negatively valenced emotions,
      such as fear, anger, and disgust.

PMID- 29022461
TI  - Facilitating the Furrowed Brow: An Unobtrusive Test of the Facial Feedback
      Hypothesis Applied to Unpleasant Affect.
AB  - We examined the hypothesis that muscle contractions in the face influence
      subjective emotional experience. Previously, researchers have been critical of
      experiments designed to test this facial feedback hypothesis, particularly in
      terms of methodological problems that may lead to demand characteristics. In an
      effort to surmount these methodological problems Strack, Martin, and Stepper
      (1988) developed an experimental procedure whereby subjects were induced to
      contract facial muscles involved in the production of an emotional pattern,
      without being asked to actually simulate an emotion. Specifically, subjects were
      required to hold a pen in their teeth, which unobtrusively creates a contraction
      of the zygomaticus major muscles, the muscles involved in the production of a
      human smile. This manipulation minimises the likelihood that subjects are able to
      interpret their zygomaticus contractions as representing a particular emotion,
      thereby preventing subjects from determining the purpose of the experiment.
      Strack et al. (1988) found support for the facial feedback hypothesis applied to
      pleasant affect, in that subjects in the pen-in-teeth condition rated humorous
      cartoons as being funnier than subjects in the control condition (in which
      zygomaticus contractions were inhibited). The present study represents an
      extension of this nonobtrusive methodology to an investigation of the facial
      feedback of unpleasant affect. Consistent with the Strack et al. procedure, we
      wanted to have subjects furrow their brow without actually instructing them to do
      so and without asking them to produce any emotional facial pattern at all. This
      was achieved by attaching two golf tees to the subject's brow region (just above
      the inside comer of each eye) and then instructing them to touch the tips of the
      golf tees together as part of a "divided-attention" experiment. Touching the tips
      of the golf tees together could only be achieved by a contraction of the
      corrugator supercilii muscles, the muscles involved in the production of a sad
      emotional facial pattern. Subjects reported significantly more sadness in
      response to aversive photographs while touching the tips of the golf tees
      together than under conditions which inhibited corrugator contractions. These
      results provide evidence, using a new and unobtrusive manipulation, that facial
      feedback operates for unpleasant affect to a degree similar to that previously
      found for pleasant affect.

PMID- 29022462
TI  - What do students think about the situational judgment test?

PMID- 29022464
TI  - Editorial board page for "The Clinical Neuropsychologist", Volume 7, Number 2.
AB  - This is a scanned image of the original Editorial Board page(s) for this issue.

PMID- 29022463
TI  - The association of postdoctoral programs in clinical neuropsychology (APPCN).
AB  - This paper describes the formation of the Association of Postdoctoral Programs in
      Professional Psychology (APPCN). The historical and organizational concept of
      APPCN is described and the founding members of this evolving network are
      enumerated. Conceptual and practical consultations are invited from
      neuropsychologists.

PMID- 29022465
TI  - Performance of adults ages 20 to 90 on the abbreviated Wisconsin card sorting
      test.
AB  - Studies of the potential effect of aging on Wisconsin Card Sorting Test (WCST)
      performance have found older adults to perform at an impaired level relative to
      younger adults. This study examined the sensitivity of the 64-card version of the
      WCST to age-related changes in 140 healthy adults, ages 20 to 90 years. Results
      revealed significant linear trends for age, demonstrating decreased competence on
      variables of accuracy (e.g., Total Errors, Categories) and perseveration.

PMID- 29022466
TI  - Analyzing clinical ratings of performance on pediatric neuropsychological tests.
AB  - This project examined the agreement among pediatric neuropsychologists when
      rating the functioning of normal and low-birth-weight children in seven
      neuropsychological domains. In Phase 1, two neuropsychologists rated 154
      children; in Phase 2, three neuropsychologists rated 41 children. Intraclass
      correlations of agreement in Phase 1 were: attention .39, intelligence .85,
      auditory/linguistic .82, haptic .70, visual perceptual/visuomotor .78, mnestic
      .72, and global .61. Intraclass correlations observed in Phase 2 were similar to
      those found in Phase 1 except that agreement in rating attention increased to
      .53. Linear modeling of global judgments revealed that two raters emphasized the
      auditory/linguistic, haptic, and visual perceptual/visuomotor domains in deriving
      global ratings, whereas the third emphasized the intellectual and attentional
      domains. In general, agreement among raters was sufficient to justify using
      clinical ratings to combine individual test scores into more general behavioral
      measures.

PMID- 29022467
TI  - Prescription privileges for psychologists: A professional affairs committee
      survey of division 40 members.
AB  - The Professional Affairs Committee conducted a survey of its members regarding
      the desirability of training for prescription privileges among its membership.
      While a majority of those surveyed appeared to be in favor of such training, many
      members expressed concern regarding the complexity of the training involved and
      its impact on the rigorous educational expectations already in place for clinical
      neuropsychologists.

PMID- 29022468
TI  - Comparison of deaf and hearing children on measures of selective attention in two
      age groups.
AB  - The Stroop and Posner tasks, used as measures of expressive and receptive
      attention, were administered to two age groups of deaf and hearing children. The
      purpose was to determine if developmental age would affect subjects' performance
      and to compare performance of the deaf with hearing subjects. The mean age for
      the younger deaf subjects was 9.9 years and the younger hearing subjects was 9.4
      years. The mean age for the older deaf and hearing subjects was 13.7 years each.
      The results revealed higher interference in the Stroop tasks for the younger deaf
      and hearing groups than for the older groups. There were no significant
      differences between deaf and hearing subjects' performance on the Stroop and
      Posner tasks when they were of similar age. The results indicate that the deaf
      had no difficulty compared to the hearing in either aspect of selective
      attention. It is suggested that separate norms for the Stroop and Posner tasks be
      developed based on developmental age.

PMID- 29022469
TI  - A prorating system for the wechsler memory scale-revised.
AB  - Various sensory and motor impairments may render a patient unable to complete
      certain subtests on the Wechsler Memory Scale-Revised (WMS-R). Consequently, when
      a subtest is missing from the battery, the clinician is unable to obtain one or
      more of the summary indices typically provided by the WMS-R. The present study
      used a mixed clinical sample (N = 300) to derive regression weights that may be
      used to predict a patient's performance on each of the WMS-R memory indices when
      a subtest is missing. The relative contributions of each subtest to the scale
      with which it is associated and the predictive accuracy of the regression
      equations are discussed.

PMID- 29022470
TI  - Developmental norms for the wisconsin card sorting test in 5-to 12-year-old
      children.
AB  - The Wisconsin Card Sorting Test (WCST) (Berg, 1948; Heaton, 1981) was given to
      233 five-to 12-year-old normal children. Participants' characteristics were
      balanced according to: (a) age, (b) socioeconomic status, and (c) gender. An
      academic achivement questionnaire was also administered. No significant
      differences between socioeconomic and gender groups were observed.
      Nonperseverative Errors, Errors, and Categories Achieved scores correlated with
      academic achievement in different areas. Developmental norms for the WCST are
      presented.

PMID- 29022471
TI  - Clinical discriminations and neuropsychological tests: An appeal to bayes'
      theorem.
AB  - Neuropsychological tests are routinely used to make clinical judgements regarding
      the classification, diagnosis, or prediction of subject variables. The accuracy
      of those decisions depends on the discriminant validity of the tests used. The
      traditional method of validating psychological tests by comparing the mean test
      scores of reference groups is often unrelated to actual clinical discriminations.
      Alternative measures based on Bayesian probabilities are reviewed, with specific
      application to neuropsychological assessment.

PMID- 29022472
TI  - TCN VOL. 7, No. 2: Overview: The editors.

PMID- 29022473
TI  - Hemispheric bias of the mini-mental state examination in elderly males.
AB  - In this study we examined the influence of lateralized brain lesions on Mini
      Mental State Examination (MMSE) performance using the psychometric concepts of
      intercept and slope bias. Four patient groups of elderly males (normal control,
      right-hemisphere stroke, left-hemisphere stroke, and dementia) were studied.
      Right-and left-hemisphere stroke groups were equated for global level of
      neuropsychological impairment independently of their MMSE performances. Results
      indicated that the right-hemisphere stroke patients' MMSE scores did not differ
      from those of controls but were significantly superior to the left-hemisphere
      stroke and dementia patients' MMSE performances. Additionally, correlations
      between the MMSE and three neuropsychological composite measures assessing
      global, verbal, and nonverbal skills, demonstrated poor correspondence among
      patients with lateralized lesions, especially those with right-hemisphere brain
      dysfunction. Results are interpreted as supporting the presence of both intercept
      and slope bias when the MMSE is used with patients having unilateral lesions.

PMID- 29022474
TI  - Awareness of behavioral limitations after traumatic brain injury: A cross
      cultural study of New Zealand maoris and non-maoris.
AB  - Forty-one New Zealand traumatic brain injury (TBI) patients were studied using
      the Patient Competency Rating Scale (PCRS) and selected neuropsychological tests.
      An attempt was made to replicate earlier reported findings in American TBI
      patients and determine if cultural factors influence self-perceptions (i.e.,
      awareness) of impairments after brain injury. TBI patients with Maori ancestry
      were compared to New Zealanders with non-Maori (English) ancestry. Both groups
      showed no correlation between their actual neuropsychological status and self
      reports of behavioral competency. In contrast, the ratings of their relatives
      concerning their behavioral competency were correlated with the patient's
      neuropsychological test performance. Maori TBI patients reported less behavioral
      competency than non-Maori TBI patients. Non-Maori TBI patients' performance on
      the PCRS replicated the findings obtained with American TBI patients. An earlier
      finding of slow speed of left-hand finger tapping in patients who overestimate
      their behavioral competency was not replicated, but a confounding of ethnicity
      and finger-tapping speed was observed. Brain damage may contribute to patients'
      misperceptions of their behavioral competency, but cultural factors also seem to
      play an important role.

PMID- 29022475
TI  - Logical memory in the wechsler memory scales - does the order of passages affect
      difficulty in an university sample?
AB  - The relative difficulty of the logical memory passages on WMS-1, WMS-2, and WMS-R
      were investigated in different orders of presentation within and between test
      forms. No evidence of order effects on difficulty level was obtained though, as
      expected, the second passage on WMS-1 was the most difficult over all orders. The
      first passages on WMS-1 and WMS-2 and both passages on WMS-R appear to be of
      equivalent difficulty.

PMID- 29022476
TI  - Spurious WAIS-R cholinergic profiles in schizophrenia.
AB  - The Fuld (1984) cholinergic profile based on the WAIS and WAIS-R age scaled
      scores has been shown to have moderate sensitivity and varying degrees of
      specificity in identifying dementia of the Alzheimer's type. The utility of this
      algorithm has increasingly been in doubt. The present study used young, well
      diagnosed schizophrenic inpatients, a nondemented population with known cognitive
      deficits, to examine the specificity of the Fuld profile and its relationship to
      demographic and neuropsychological indices. The results found that the subjects
      who demonstrated a positive cholinergic profile (15%) did not differ
      neuropsychologically from the remaining sample. In the absence of other
      discriminating neuropsychological functions, the index is merely an artifact of
      relatively higher verbal abilities in the context of lower performance skills.

PMID- 29022477
TI  - New adult age-and education-correction norms for the benton visual retention
      test.
AB  - Adult age-and education-corrected norms for the Revised Visual Retention Test
      (BVRT) are presented. Our sample included 1,128 healthy individuals, ranging in
      age across the adult life span. Stepwise multiple regression analyses
      demonstrated significant negative associations between age and BVRT performance
      and significant positive associations between education and BVRT performance.
      Gender was not associated with performance. Both the regression equations, for
      predicting expected levels of performance in individuals, and tabular data are
      presented.

PMID- 29022478
TI  - Proposed standard of professional practice: Neuropsychological reports display
      all quantitative data.
AB  - It is proposed that the standard for the profession be that neuropsychological
      reports include a display of all quantitative findings. Arguments in favor of the
      proposal are presented.

PMID- 29022479
TI  - Utility of a modified version of the wisconsin card sorting test in the detection
      of dementia of the alzheimer type.
AB  - Nelson's (1976) modified version of the Wisconsin Card Sorting Test (mWCST) was
      administered to 23 patients with mild dementia of the Alzheimer type (DAT), 33
      moderate DAT patients, 31 severe DAT patients, and 75 demographically matched
      normal control (NC) subjects. DAT patients attained fewer categories and
      committed significantly more perseverative errors than NC subjects. None of the
      DAT patient subgroups differed in the number of perseverative errors committed,
      but the severe DAT patients attained significantly fewer categories than either
      the mild or moderate DAT patients. Receiver operating characteristic [ROC] curves
      were plotted to determine which among several of the measures provided the best
      sensitivity (i.e., correctly identified patients) and specificity (i.e.,
      correctly identified normal controls). The number of categories attained was
      found to be the best discriminative measure for the entire sample of DAT
      patients, whereas the number of perseverative errors provided the best
      discriminability in mild DAT patients. Findings suggest that Nelson's original
      modification of the WCST is sensitive in the early detection of DAT.

PMID- 29022480
TI  - Evaluation of serum autoantibodies against tumor-associated antigens as
      biomarkers in lung cancer.
AB  - We evaluated autoantibodies against nine tumor-associated antigens, including
      p62, p16, Koc, p53, Cyclin B1, Cyclin E, Survivin, HCC1, and RalA as serological
      markers in lung cancer. Enzyme-linked immunosorbent assay (ELISA) was used to
      detect autoantibodies in sera from 50 lung cancer patients and 42 normal
      controls. Then, four tumor-associated antigens of higher values were selected and
      validated in sera from validation group. Western blot and serum absorption test
      were used to confirm positive findings from ELISA. When cutoff values were set as
      mean optical density values plus 3 standard deviation of normal controls, the
      positive rate of autoantibodies against four tumor-associated antigens (Survivin,
      Cyclin B1, HCC1, and p53) reached 32%, 20%, 22%, and 18%, with area under the
      curve values of 0.653, 0.767, 0.622, and 0.623 in sera from 50 lung cancer,
      respectively (all p < 0.05). Results from the validation group confirmed the
      results. When lung cancer patients were divided by their clinicopathological
      characteristics into different subgroups, we have found that serum anti-Cyclin B1
      and anti-HCC1 autoantibodies increased in stages 1, 2, and 3 lung cancer; anti
      Survivin autoantibodies increased in stages 2 and 3 lung cancer; and anti-p53
      autoantibody only increased in stage 1 when compared with their corresponding
      levels in controls (all p < 0.05). Serum anti-Cyclin B1 and anti-Survivin
      autoantibodies increased with disease histological grade 2 and 3 (both p < 0.05).
      And higher serum level of anti-p53 autoantibodies is positively associated with
      tumor size. Parallel utilization of these four anti-tumor-associated antigens
      (any positive) can increase sensitivity to 65.0% at 100% specificity with area
      under the curve of 0.908 ( p < 0.001) in lung cancer detection in validation
      group. Our results suggest that autoantibodies against these four tumor
      associated antigens have higher values in lung cancer detection, and serum anti
      Cyclin-B1 has the potential to serve as novel non-invasive biomarkers in early
      stage lung cancer.

PMID- 29022481
TI  - Intra and interobserver variability of intrapartum transperineal ultrasound
      measurements with contraction and pushing.
AB  - The aim of this study was to evaluate the inter- and intraobserver correlation of
      the different intrapartum-transperineal-ultrasound-parameters(ITU) (angle of
      progression (AoP), progression-distance (PD), head-direction (HD), midline-angle
      (MLA) and head-perineum distance (HPD)) with contraction and pushing. We
      evaluated 28 nulliparous women at full dilatation under epidural analgesia. We
      performed a transperineal ultrasound evaluating AoP and PD in the longitudinal
      plane, and MLA and HPD in the transverse plane. Interclass correlation
      coefficients (ICC) with 95% CIs and Bland-Altman analysis were used to assess
      intra- and interobserver measurement's repeatability. The ICC of the ITU for the
      same observer was adequate for all the parameters (p < .005) AoP 0.98 (95%CI,
      0.96-0.99), PD 0.98 (95%CI, 0.97-0.99), MLA 0.99 (95%CI, 0.97-0.99), HPD 0.96
      (95%CI, 0.88-0.99). The ICC of the ITU for interobserver was: AoP 0.93 (95%CI,
      0.79-0.98), PD 0.92 (95%CI, 0.76-0.97), MLA 0.77 (95%CI, 0.42-0.92), HPD 0.47
      (95%CI, -0.12-0.8). The HD had an interobserver correlation of 0.53 (95%CI, 0.1
      0.9) (Kappa C). The mean difference of the AoP was 2.42 degrees , of the PD 1 mm
      and 0.28 degrees  MLA (Bland-Altman test). ITU has an adequate intra- and
      interobserver correlation for its use with contraction and pushing under epidural
      analgesia. Impact statement What is already known on this subject: The
      intrapartum transperineal ultrasound parameters can be used with contraction and
      pushing under epidural analgesia. What the results of this study add to what we
      know: ITU may be used to evaluate the difficulty of instrumental delivery/to
      evaluate the difficulty of instrumentation in vaginal operative deliveries and
      this study concludes that ITU is reproducible during uterine contraction with
      pushing. What the implications are of these findings for clinical practice and/or
      further research: Therefore, ITU could be used without difficulty with an
      adequate intra- and interobserver correlation for the prediction of
      instrumentation difficulty in operative vaginal deliveries.

PMID- 29022482
TI  - OCT4B2, a novel alternative spliced variant of OCT4, is significantly upregulated
      under heat-stress condition and downregulated in differentiated cells.
AB  - OCT4 is a crucial transcription factor that maintains self-renewal and
      pluripotency of embryonic stem and embryonic carcinoma cells. The human OCT4 gene
      can generate at least three variants (OCT4A, OCT4B, and OCTB1) via alternative
      splicing and alternative promoters. It has been previously reported that OCT4A is
      the main isoform, retaining stemness state in embryonic stem and embryonic
      carcinoma cells. There are several reports on the expression of OCT4A, OCT4B, and
      OCT4B1 in some cancers and tumor cells. The expression of OCT4 in cancer tissues
      and cell lines appeared to be highly controversial since it was believed that
      OCT4 is exclusively expressed in embryonic stem/embryonic carcinoma cells. Here,
      we are reporting the detection of a novel alternatively spliced variant of OCT4,
      OCT4B2, in several pluripotent and tumor cell lines. Moreover, the expression
      pattern of OCT4B2 in the course of neural differentiation of NT2 and NCCIT,
      embryonic carcinoma cells, was similar to that of OCT4A. OCT4B2 was highly
      expressed in undifferentiated cells; however, its expression was sharply
      downregulated upon induction of differentiation. Overexpression of OCT4B2 did not
      affect the distribution of cells in different cell-cycle phases of transfected
      cells, compared to the mock transfected cells. Interestingly, the expression of
      OCT4B2 transcript was elevated under the heat-shock induction. In conclusion, we
      are reporting a new variant of OCT4, which is expressed under different
      physiological conditions. The finding shed more light on complexity of OCT4
      expression and functions.

PMID- 29022483
TI  - In vitro combined effect of Doxorubicin and sulfonated zinc Phthalocyanine
      mediated photodynamic therapy on MCF-7 breast cancer cells.
AB  - Doxorubicin is a broad-spectrum antibiotic and anticancer drug used to treat a
      variety of human malignancies like breast cancer and leukaemia. Unfortunately, a
      dose-dependent side effect of this drug is common, representing a major obstacle
      to its use despite its therapeutic efficacy. Photodynamic therapy is an emerging
      non-invasive potential adjuvant for conventional cancer treatment. In an attempt
      to circumvent the dose-limiting effect of doxorubicin, this study aimed to
      investigate cellular anticancer activity of doxorubicin and sulfonated zinc
      phthalocyanine-mediated photodynamic therapy on MCF-7 cells alone and in
      combination. Furthermore, we investigated the cell death pathway resulting from
      the combination treatment. MCF-7 cells were incubated with 0.5 uM concentration
      of doxorubicin for 20 h, afterwards, various concentrations of sulfonated zinc
      phthalocyanine were added and incubated for 4 h. Cells were irradiated using a
      681.5 nm diode laser at 4.53 mW/cm2 for 18 min 24 s (5 J/cm2). Cell viability and
      proliferation were measured using trypan blue assay and homogeneous adenosine
      triphosphate quantitation assay, respectively, while qualitative changes in
      cellular morphology were observed under inverted light microscopy. Cellular DNA
      damage was assessed under fluorescent microscopy and Annexin V/propidium iodide
      stain was used to investigate the cell death pathway. Findings from this study
      shown that combined treatment with doxorubicin and photodynamic therapy was more
      effective in inhibiting the proliferation and growth of MCF-7 cells. Overall, the
      results indicate that combination of smaller dose of doxorubicin with
      photodynamic therapy is a promising combined treatment strategy for breast
      carcinoma. However, this combination warrants further investigation.

PMID- 29022485
TI  - Prevalence of betaIII-tubulin (TUBB3) expression in human normal tissues and
      cancers.
AB  - Microtubules are multifunctional cytoskeletal proteins that are involved in
      crucial cellular roles including maintenance of cell shape, intracellular
      transport, meiosis, and mitosis. Class III beta-tubulin (betaIII-tubulin, also
      known as TUBB3) is a microtubule protein, normally expressed in cells of neuronal
      origin. Its expression was also reported in various other tumor types, such as
      several types of lung cancer, ovarian cancer, and esophageal cancer. TUBB3 is of
      clinical relevance as overexpression has been linked to poor response to
      microtubule-targeting anti-cancer drugs such as taxanes. To systematically
      investigate the epidemiology of TUBB3 expression in normal and neoplastic
      tissues, we used tissue microarrays for analyzing the immunohistochemically
      detectable expression of TUBB3 in 3911 tissue samples from 100 different tumor
      categories and 76 different normal tissue types. At least 1 tumor with weak
      expression could be found in 93 of 100 (93%) different tumor types, and all these
      93 entities also had at least 1 tumor with strong positivity. In normal tissues,
      a particularly strong expression was found in neurons of the brain, endothelium
      of blood vessels, fibroblasts, spermatogenic cells, stroma cells, endocrine
      cells, and acidophilic cells of the pituitary gland. In tumors, strong TUBB3
      expression was most frequently found in various brain tumors (85%-100%), lung
      cancer (35%-80%), pancreatic adenocarcinoma (50%), renal cell carcinoma (15%
      80%), and malignant melanoma (77%). In summary, these results identify a broad
      spectrum of cancers that can at least sporadically express TUBB3. Testing of
      TUBB3 in cancer types eligible for taxane-based therapies could be helpful to
      identify patients who might best benefit from this treatment.

PMID- 29022484
TI  - Prognostic implication of simultaneous anemia and lymphopenia during concurrent
      chemoradiotherapy in cervical squamous cell carcinoma.
AB  - Radioresistance often leads to poor survival in concurrent chemoradiotherapy
      treated cervical squamous cell carcinoma, and reliable biomarkers can improve
      prognosis. We compared the prognostic potential of hemoglobin, absolute
      neutrophil count, and absolute lymphocyte count with that of squamous cell
      carcinoma antigen in concurrent chemoradiotherapy-treated squamous cell
      carcinoma. We analyzed 152 patients with concurrent chemoradiotherapy and high
      dose-rate intracavitary brachytherapy-treated cervical squamous cell carcinoma.
      Hemoglobin, absolute neutrophil count, absolute lymphocyte count, and squamous
      cell carcinoma antigen were quantitated and correlated with survival, using Cox
      regression, receiver operating characteristic curve analysis, and Kaplan-Meier
      plots. Both hemoglobin and absolute lymphocyte count in the second week of
      concurrent chemoradiotherapy (Hb2 and ALC2) and squamous cell carcinoma antigen
      in the third week of concurrent chemoradiotherapy (mid-squamous cell carcinoma
      antigen) correlated significantly with disease-specific survival and progression
      free survival. The ratio of high-dose-rate intracavitary brachytherapy dose to
      total dose (high-dose-rate intracavitary brachytherapy ratio) correlated
      significantly with progression-free survival. Patients with both low Hb2 (<=11
      g/dL) and ALC2 (<=639 cells/uL) showed a lower 5-year disease-specific survival
      rate than those with high Hb2 and/or ALC2, regardless of mid-squamous cell
      carcinoma antigen (mid-squamous cell carcinoma antigen: <=4.7 ng/mL; 5-year
      disease-specific survival rate: 85.5% vs 94.6%, p = 0.0096, and mid-squamous cell
      carcinoma antigen: >4.7 ng/mL; 5-year disease-specific survival rate: 43.8% vs
      66.7%, p = 0.192). When both Hb2 and ALC2 were low, the low high-dose-rate
      intracavitary brachytherapy ratio (<=0.43) subgroup displayed significantly lower
      5-year disease-specific survival rate compared to the subgroup high high-dose
      rate intracavitary brachytherapy ratio (>0.43) (62.5% vs 88.2%, p = 0.0067).
      Patients with both anemia and lymphopenia during concurrent chemoradiotherapy
      showed poor survival, independent of mid-squamous cell carcinoma antigen, and
      escalating high-dose-rate intracavitary brachytherapy ratio might improve
      survival.

PMID- 29022486
TI  - Association of vitamin D receptor gene polymorphisms with breast cancer risk in
      an Egyptian population.
AB  - This study aimed to explore whether genetic polymorphisms in vitamin D receptor
      are correlated to the breast cancer prevalence in an Egyptian population.
      Polymerase chain reaction-restriction fragment polymorphism was used to genotype
      three frequently analyzed vitamin D receptor gene single-nucleotide polymorphisms
      (rs1544410, rs7975232, and rs731236) and were identified by sequencing analysis.
      This is the first study that recorded a new single-nucleotide polymorphism in
      ApaI genotype within an Egyptian population and was registered with the accession
      number KY859868. The authors found that TC in rs731236, and TG in KY859868 single
      nucleotide polymorphism showed significant distribution differences with an
      increased risk of breast cancer ( p < 0.05, odds ratio = 3.71, 95% confidence
      interval: 1.04-13.28 and p < 0.001, odds ratio = 7.05, 95% confidence interval:
      2.02-24, respectively) compared with the wild-type TT genotype carriers in both
      single-nucleotide polymorphisms. In addition, the distribution frequencies of
      haplotypes ACT, GTT, and ATT in the patients group were significant, where ATT
      haplotype was associated with the highest breast cancer risk among all other
      haplotypes in the patients group ( p = 0.0023, odds ratio = 1.72, 95% confidence
      interval: 1.24-2.437). In conclusion, vitamin D receptors ApaI and TaqI confer
      high breast cancer susceptibility, particularly in Egyptians females carrying
      haplotype ATT. However, further studies focusing on the vitamin D receptor
      variants and haplotypes effects on vitamin D and vitamin D receptor
      concentrations, activities, and functionalities are needed.

PMID- 29022487
TI  - Influence of autocrine growth hormone on NF-kappaB activation leading to
      epithelial-mesenchymal transition of mammary carcinoma.
AB  - Progression of breast cancers often depends on hormones among which human growth
      hormone is prominently involved in breast cancer progression. Earlier studies
      have reported constitutive activation of nuclear factor-kappaB, a key regulator
      of growth hormone receptor-mediated signaling pathway in breast carcinoma, but
      the precise molecular mechanisms are still elusive. In this study, we
      investigated the effect of human growth hormone on nuclear factor-kappaB
      activation and epithelial-mesenchymal transition in breast carcinoma. Our results
      explored that autocrine production of human growth hormone enhances cellular
      proliferation by the activation of nuclear factor-kappaB (65 kDa) and
      downregulation of E-cadherin expression. Furthermore, enhanced nuclear factor
      kappaB expression significantly increases cell proliferation and diminishes
      apoptosis in MCF-7 cell line. Increased expression of nuclear factor-kappaB
      significantly enhances mammary carcinoma cell migration and invasion stimulated
      by autocrine human growth hormone, which results in epithelial-mesenchymal
      transition of MCF-7 cells. In conclusion, our study revealed the influence of
      human growth hormone on nuclear factor-kappaB activity and epithelial-mesenchymal
      transition in mammary carcinoma. Our findings will help to understand molecular
      role of "growth hormone-nuclear factor-kappaB axis" in mammary carcinogenesis
      which may facilitate the discovery of suitable pathway inhibitors for disease
      treatment.

PMID- 29022488
TI  - Characterization of immortalized human mammary epithelial cell line HMEC 2.6.
AB  - Primary human mammary epithelial cells have a limited life span which makes it
      difficult to study them in vitro for most purposes. To overcome this problem, we
      have developed a cell line that was immortalized using defined genetic elements,
      and we have characterized this immortalized non-tumorigenic human mammary
      epithelial cell line to establish it as a potential model system. human mammary
      epithelial cells were obtained from a healthy individual undergoing reduction
      mammoplasty at SIU School of Medicine. The cells were transduced with CDK4R24C
      followed by transduction with human telomerase reverse transcriptase. Post all
      manipulation, the cells displayed a normal cell cycle phase distribution and were
      near diploid in nature, which was confirmed by flow cytometry and karyotyping. In
      vitro studies showed that the cells were anchorage dependent and were non
      invasive in nature. The cell line expressed basal epithelial markers such as
      cytokeratin 7, CD10, and p63 and was negative for the expression of estrogen
      receptor and progesterone receptor. Upon G-band karyotyping, the cell line
      displayed the presence of a few cytogenic abnormalities, including trisomy 20 and
      trisomy 7, which are also commonly present in other immortalized mammary cell
      lines. Furthermore, the benign nature of these cells was confirmed by multiple in
      vitro and in vivo experiments. Therefore, we think that this cell line could
      serve as a good model to understand the molecular mechanisms involved in the
      development and progression of breast cancer and to also assess the effect of
      novel therapeutics on human mammary epithelial cells.

PMID- 29022489
TI  - ADAR1 expression is associated with tumour-infiltrating lymphocytes in triple
      negative breast cancer.
AB  - Tumours with a high mutation burden exhibit considerable neoantigens and tumour
      infiltrating lymphocytes. RNA editing by ADAR1 is a source of changes in epitope.
      However, ADAR1 expression in cancer cells and tumour-infiltrating lymphocyte
      levels in triple-negative breast cancer have not been well evaluated. We
      immunohistochemically examined ADAR1 expression in 681 triple-negative breast
      cancer patients and analysed their clinicopathological characteristics. We also
      analysed basal-like tumours using The Cancer Genome Atlas data. Among the 681
      triple-negative breast cancer patients, 45.8% demonstrated high ADAR1 expression.
      Tumours with high ADAR1 expression exhibited high tumour-infiltrating lymphocyte
      levels, considerable CD8 + T lymphocyte infiltration, high histological grade and
      high expression of interferon-related proteins, including HLA-ABC, MxA and PKR.
      Among patients with lymph node metastasis, those with high tumour-infiltrating
      lymphocyte levels and low ADAR1 expression demonstrated the best disease-free
      survival. The Cancer Genome Atlas data analysis of basal-like tumours revealed
      significant positive correlation between ADAR1 and CD8B expression and positive
      association of high ADAR1 expression with immune responses and apoptosis
      pathways. We detected high ADAR1 expression in half of the triple-negative breast
      cancer patients. In addition to DNA mutations, RNA editing can be related to
      neoantigens; hence, we need to explore non-synonymous mutations exclusively found
      using RNA sequencing data to identify clinically relevant neoantigens.

PMID- 29022490
TI  - The German Federal Supreme Court also granted a compulsory patent license for the
      first time in its history.

PMID- 29022491
TI  - Waste-to-energy: A review of life cycle assessment and its extension methods.
AB  - This article proposes a comprehensive review of evaluation tools based on life
      cycle thinking, as applied to waste-to-energy. Habitually, life cycle assessment
      is adopted to assess environmental burdens associated with waste-to-energy
      initiatives. Based on this framework, several extension methods have been
      developed to focus on specific aspects: Exergetic life cycle assessment for
      reducing resource depletion, life cycle costing for evaluating its economic
      burden, and social life cycle assessment for recording its social impacts.
      Additionally, the environment-energy-economy model integrates both life cycle
      assessment and life cycle costing methods and judges simultaneously these three
      features for sustainable waste-to-energy conversion. Life cycle assessment is
      sufficiently developed on waste-to-energy with concrete data inventory and
      sensitivity analysis, although the data and model uncertainty are unavoidable.
      Compared with life cycle assessment, only a few evaluations are conducted to
      waste-to-energy techniques by using extension methods and its methodology and
      application need to be further developed. Finally, this article succinctly
      summarises some recommendations for further research.

PMID- 29022492
TI  - Platelet aggregation impacts thrombin generation assessed by calibrated automated
      thrombography.
AB  - A calibrated automated thrombogram (CAT) is performed usually with human platelet
      free plasma (PFP) but may be more relevant with platelet-rich plasma (PRP). In
      this case, platelets are not stimulated by subendothelial molecules like
      collagen. Our aim was to assess the consequence of strong (collagen) or weak
      (ADP) induction of platelet release and aggregation on thrombin generation.
      Platelet aggregation in PRP was triggered with 10 ug/mL collagen or 10 uM ADP
      using a lumi-aggregometer. Thrombin generation curves were monitored by CAT in
      different conditions: PRP, PRP with activated platelets (actPRP), aggregated PRP
      (agPRP), aggregated platelets resuspended in autologous PFP (resPRP), PFP and PFP
      obtained after aggregation (agPFP). We found a 3-fold shortening of the lag time
      and time to peak and a marked increase in velocity and thrombin peak without
      changes in endogenous thrombin potential (ETP) in agPRP with both agonists
      compared with PRP. The same holds true in agPFP but with a marked increase in ETP
      compared with PFP. Similar changes in the kinetics of thrombin generation were
      observed with actPRP-collagen and to a lesser extent in resPRP-collagen compared
      with PRP. By contrast, there were no modifications of the thrombin generation
      curves in actPRP-ADP. Alpha-2-macroglobin-thrombin complexes were unchanged in
      the different PRP conditions but were increased in PFP prepared from agPFP
      compared to control PFP. Platelet aggregation during activation by agonists other
      than thrombin did not increase thrombin generation but accelerated its kinetics
      mainly via platelet content release and platelet-derived extracellular vesicules
      formation. In diseases characterized by altered platelet granule content or
      release as well as altered platelet activation, a platelet aggregation step prior
      to CAT analysis may be clinically relevant to improve laboratory estimation of
      the bleeding/thrombotic balance.

PMID- 29022493
TI  - Immunonutrition before esophagectomy: Impact on immune surveillance mechanisms.
AB  - Preoperative oral immunonutrition was demonstrated to improve immune response and
      to decrease the infection rate in patients with cancer. This study aimed to
      assess how immunonutrition could influence the immune cell response in the
      mucosal microenvironment of esophageal adenocarcinoma. Therefore, A prospective
      cohort of consecutive patients undergoing esophagectomy for esophageal
      adenocarcinoma was enrolled. A subgroup of them was given preoperative oral
      immunonutrition with Oral Impact(r) and was compared to those who received no
      preoperative supplementation. Mucosal samples from healthy esophagus were
      obtained at esophagectomy. Histology, immunohistochemistry, gene expression
      analysis, and cytofluorimetry were performed. Markers of activation of antigen
      presenting cells (CD80, CD86, and HLA-I), innate immunity (TLR4 and MyD88), and
      cytotoxic lymphocyte infiltration and activation (CD8, CD38, CD69, and CD107)
      were measured. In all, 50 patients received preoperative Oral Impact(r) and 129
      patients received no nutritional support. CD80, CD86, MyD88, and CD69 messenger
      RNA expression was significantly increased in patients receiving immunonutrition
      compared to controls. In the subgroup of patients with stages I-II cancer, the
      rate of epithelial cells expressing CD80 and HLA-ABC was significantly higher in
      those receiving immunonutrition compared to controls as well as CD8+ CD28+ cell
      rate. Immunonutrition administration before surgery was significantly associated
      to increased degranulating CD8 and natural killer cells (CD107+) infiltrating the
      healthy esophageal mucosa. All the comparisons were adjusted for cancer stage and
      preoperative therapy. In conclusion, in healthy esophageal mucosa of patients
      undergoing esophagectomy, a 5-day course of immunonutrition enhances expression
      of antigen-presenting cells activity and increased CD8+ T cell activation and
      degranulating activity. Further studies are warranted to understand the clinical
      implication in terms of cancer recurrence.

PMID- 29022494
TI  - Colder environments are associated with a greater cancer incidence in the female
      population of the United States.
AB  - Cancer incidence and/or mortality among individuals varies with diet, socio
      culture, ethnicity, race, gender, and age. Similarly, environmental temperature
      modulates many biological functions. To study the effect of environment
      temperature on cancer incidence, the US population was selected. Because, county
      wise cancer incidence rate data of various anatomical site-specific cancers and
      different races/ethnicities for both males and females are available. Moreover,
      the differences amongst the aforementioned factors among individuals are much
      less, as compared to the world population. Statistical analysis showed a negative
      correlation between the average annual temperature and cancer incidence rate at
      all anatomical sites and individually for 13 types (out of 16 types) of
      anatomical site-specific cancer incidence rates (e.g. uterine, bladder, thyroid,
      breast, esophagus, ovary, melanoma, non-Hodgkin lymphoma, leukemia, brain,
      pancreas, etc.) for females. Further analysis found a similar inverse trend in
      all races/ethnicities of the female population but not in all male
      races/ethnicities or anatomical site-specific cancers. Moreover, the majority of
      the counties having the top-most cancer incidence rate in females are located
      above the latitude 36.5 degrees N. These findings indicate that living in a cold
      county in the United States might have a higher risk of cancer irrespective of
      cancer type (except cervical and liver) and races/ethnicities for females but not
      in all such cases for the male population.

PMID- 29022495
TI  - Genetic polymorphisms of HOTAIR gene are associated with the risk of breast
      cancer in a sample of southeast Iranian population.
AB  - There is an increasing body of evidence which highlights the critical functions
      of long non-coding RNAs in the carcinogenicity mechanism of a variety of cancers.
      It has been reported that HOX transcript antisense intergenic RNA, a member of
      long non-coding RNA family, increases breast cancer risk. To date, no data
      regarding the association between HOX transcript antisense intergenic RNA
      polymorphisms and the risk of breast cancer development has been reported in
      Iran. Here, we examine the possible association between HOX transcript antisense
      intergenic RNA gene polymorphisms and breast cancer in a sample of southeast
      Iranian female population. The HOX transcript antisense intergenic RNA rs920778,
      rs12826786, rs4759314, and 1899663 gene polymorphisms were genotyped in 220 cases
      and 231 controls by polymerase chain reaction-restriction fragment length
      polymorphism. Our findings indicated that rs920778 polymorphism has significant
      positive association with breast cancer; rs12826786 and rs1899663 polymorphisms
      demonstrated significant negative association with breast cancer; and the
      rs4759314 variant was not associated with breast cancer risk. Haplotype analysis
      revealed that TGAC, CTAT, and TTAT haplotypes significantly decreased the risk of
      breast cancer compared with rs920778T/rs1899663G/rs4759314A/rs12826786T
      haplotype. In conclusion, we investigated only four variants of HOX transcript
      antisense intergenic RNA gene, and the findings suggest that HOX transcript
      antisense intergenic RNA rs920778, rs12826786, and rs1899663 polymorphisms may be
      associated with breast cancer risk in a sample of southeast Iranian population.
      Further replication studies with other polymorphisms of HOX transcript antisense
      intergenic RNA gene involving a greater sample size and different ethnicities are
      necessary to verify our findings.

PMID- 29022496
TI  - Antitumor and radiosensitizing synergistic effects of apigenin and
      cryptotanshinone against solid Ehrlich carcinoma in female mice.
AB  - Considerable attention has been paid to the introduction of novel naturally
      occurring plant-derived radiosensitizer compounds in order to augment the
      radiation efficacy and improve the treatment outcome of different tumors. This
      study was therefore undertaken to evaluate the antitumor, antiangiogeneic, and
      synergistic radiosensitizing effects of apigenin, a dietary flavonoid, and/or
      cryptotanshinone, a terpenoid isolated from the roots of Salvia miltiorrhiza,
      against the growth of solid Ehrlich carcinoma in female mice. Apigenin (50 mg/kg
      body weight) and/or cryptotanshinone (40 mg/kg body weight) was intraperitoneally
      (i.p.) injected into non-irradiated or gamma-irradiated (6.5 Gy whole-body gamma
      irradiation) solid Ehrlich carcinoma-bearing mice for 30 consecutive days.
      Investigations included molecular targets involved in proliferation,
      inflammation, angiogenesis, and tumor invasiveness. Treatment with apigenin
      and/or cryptotanshinone significantly suppressed the growth of solid Ehrlich
      carcinoma tumors and demonstrated a synergistic radiosensitizing efficacy
      together with gamma-irradiation. These effects were achieved through
      downregulating the expression of angiogenic and lymphangiogenic regulators,
      including signal transducer and activator of transcription 3, vascular
      endothelial growth factor C, and tumor necrosis factor alpha, suppressing matrix
      metalloproteinase-2 and -9 activities, which play a key role in tumor invasion
      and metastasis, and enhancing apoptosis via inducing cleaved caspase-3 and
      granzyme B levels. Histological findings of solid Ehrlich carcinoma tumors
      verified the recorded data. In conclusion, a synergistic radiosensitizing
      efficacy for apigenin and cryptotanshinone was demonstrated against Ehrlich
      carcinoma in the current in vivo murine model, representing therefore a potential
      therapeutic strategy for increasing the radiation response of solid tumors.

PMID- 29022497
TI  - Estrogen-induced disruption of intracellular iron metabolism leads to oxidative
      stress, membrane damage, and cell cycle arrest in MCF-7 cells.
AB  - It is well established that several forms of cancer associate with significant
      iron overload. Recent studies have suggested that estrogen (E2) disrupts
      intracellular iron homeostasis by reducing hepcidin synthesis and maintaining
      ferroportin integrity. Here, the ability of E2 to alter intracellular iron status
      and cell growth potential was investigated in MCF-7 cells treated with increasing
      concentrations of E2. Treated cells were assessed for intracellular iron status,
      the expression of key proteins involved in iron metabolism, oxidative stress,
      cell survival, growth, and apoptosis. E2 treatment resulted in a significant
      reduction in hepcidin expression and a significant increase in hypoxia-inducible
      factor 1 alpha, ferroportin, transferrin receptor, and ferritin expression; a
      transient decrease in labile iron pool; and a significant increase in total
      intracellular iron content mainly at 20 nM/48 h E2 dose. Treated cells also
      showed increased total glutathione and oxidized glutathione levels, increased
      superoxide dismutase activity, and increased hemoxygenase 1 expression. Treatment
      with E2 at 20 nM for 48 h resulted in a significant reduction in cell growth
      (0.35/1 migration rate) and decreased cell survival (<80%) as compared with
      controls. Survivin expression significantly increased at 24 h post treatment with
      5, 10, or 20 nM; however, that of gamma-H2AX increased only after survivin levels
      dropped and only at the 20 nM E2 dose. Minimal upregulation and splitting of
      caspase 9 was only evident in cells treated with 20 nM E2; no changes in caspase
      3 expression were evident. Although Annexin V staining studies showed that E2
      treatment did not induce apoptosis, scanning electron microscopy studies showed
      marked membrane blebbing at 20 nM/48 h of E2. These findings suggest that
      estrogen treatment disrupts intracellular iron metabolism and precipitates
      adverse effects concerning cell viability, membrane integrity, and growth
      potential.

PMID- 29022498
TI  - ATP-binding cassette exporters: structure and mechanism with a focus on P
      glycoprotein and MRP1.
AB  - The majority of proteins that belong to the ATP-binding cassette (ABC)
      superfamily are transporters that mediate the efflux of substrates from cells.
      These exporters include multidrug resistance proteins of the ABCB and ABCC
      subfamilies, such as P-glycoprotein (Pgp) and MRP1, respectively. These proteins
      are not only involved in the resistance of cancer to cytotoxic agents, but also
      in the protection from endo and xenobiotics, and the determination of drug
      pharmacokinetics, as well as in the pathophysiology of a variety of disorders.
      Here, we present a review of the information available on ABC exporters, with a
      focus on Pgp, MRP1 and related proteins. We describe tissue localization and
      function of these transporters in health and disease, and discuss the mechanisms
      of substrate transport. We also correlate recent structural information with the
      function of the exporters, and discuss details of their molecular mechanism with
      a focus on the nucleotide-binding domains.

PMID- 29022499
TI  - The Medicinal Chemistry of Therapeutic Peptides: Recent Developments in Synthesis
      and Design Optimizations.
AB  - Peptide therapeutics have made tremendous progress in the past decade. Many of
      the inherent weaknesses of peptides which hampered their development as
      therapeutics are now more or less effectively tackled with recent scientific and
      technological advancements in integrated drug discovery settings. These include
      recent developments in synthetic organic chemistry, high-throughput recombinant
      production strategies, high-resolution analytical methods, high-throughput
      screening options, ingenious drug delivery strategies and novel formulation
      preparations. Here, we will briefly describe the key methodologies and strategies
      used in the therapeutic peptide development processes with select examples of the
      most recent developments in the field. The aim of this review is to highlight the
      viable options a medicinal chemist may consider in order to improve a specific
      pharmacological property of interest in a peptide lead entity and thereby
      rationally assess the therapeutic potential this class of molecules possesses
      while they are traditionally (and incorrectly) considered 'undruggable'.

PMID- 29022500
TI  - Biomarkers of Atrial Fibrillation in Metabolic Syndrome.
AB  - Whether the increased atrial fibrillation (AF) risk in metabolic syndrome (MetS)
      patients is due to the syndrome as a whole or simply the sum of the risks of its
      individual component parts is still obscure. These two clinical entities share
      many pathophysiological links and thus distinction between a casual observation
      and a significant association is difficult. Biomarkers associated with
      pathogenesis of AF in the context of MetS have the ability to refine future risk
      prediction. In the present review we identify circulating substances that could
      be regarded as potential biomarkers for prediction of incident AF, or of
      cardiovascular events in the setting of AF in patients with MetS. Cardiac myocyte
      injury and stress markers (troponin and natriuretic peptides), markers of renal
      function (glomeral filtration rate, cystatin-C), and inflammation
      markers/mediators (interleukin-6, CRP) are promising biomarkers of patients with
      AF and MetS.

PMID- 29022501
TI  - Nanotechnology in Personalized Medicine: A Promising Tool for Alzheimer's Disease
      Treatment.
AB  - Alzheimer's disease (AD) is a public health priority all over the world. The
      difficulty of fighting the disease consists mostly in the complexity of symptoms
      and causes, in the still poor knowledge of its mechanisms and in the existence of
      a latent, asymptomatic, preclinical stage. Although many drugs are continuously
      screened in clinical studies for the treatment of Alzheimer's disease, the
      unexpected lack of patient response and sometimes the important adverse effects
      make it a potential field of application for personalized medicine. The aim of
      personalized medicine is the development of more patient-precise treatments based
      mostly on the knowledge of individual genetics as well as of disease progress,
      and of pharmacokinetics and metabolic response to available drugs. The
      optimization of new and more sensitive detection techniques is an important tool
      for obtaining the poll of data needed for prediction and understanding of patient
      responses. The aim of this perspective review is to propose nanotechnology as a
      valuable tool for the application of personalized medicine to AD. Research in
      bionanosensors is already providing examples with high sensitivity for core and
      new biomarkers for AD. In therapy the functionalization of nanoparticle surface
      can add specificity for biological recognition or for improving the
      bioavailability. This would allow the administration of lower doses with less
      adverse effects due to the local targeting. Taking into account the promising
      characteristics of nanoparticles as excellent candidate tools for precision
      medicine development, the establishment of better standard methods for safety
      assessment and production scale up would be desirable for the nanomaterial
      fruitful employment.

PMID- 29022502
TI  - Pathophysiological Role of Mitochondrial Potassium Channels and their Modulation
      by Drugs.
AB  - BACKGROUND: Mitochondria play a central role in ATP-generating processes. Indeed,
      in mammalian tissues, up to 90% of ATP is generated by mitochondria through the
      process of oxidative phosphorylation; furthermore, mitochondria are involved in
      multiple signal transduction pathways. A rapidly expanding body of literature has
      confirmed that mitochondria play a pivotal role in apoptosis, cardio- and neuro
      protection, and various neurodegenerative disorders, ranging from Parkinson's to
      Alzheimer's disease. Mitochondria are also the targets of multiple drugs, some of
      these are specifically designed to affect mitochondrial function, while others
      have primary targets in other cellular locations but may interact with
      mitochondria because of the presence of numerous targets on this organelle. In
      this regard, mitochondrial potassium (mitoK) channels play a critical role in
      mitochondrial function and, consequently, in the metabolism of the whole cell.
      OBJECTIVE: To describe mitoK channels from a structural point of view and
      investigate their pathophysiological roles, focusing on possible specific
      modulators that might be useful as pharmacological tools in the treatment of
      various pathologies characterized by mitoK involvement. RESULTS: mitoK channels
      play a decisive role in several pathologies, including cardiovascular diseases,
      particularly in myocardial infarction and neurodegenerative diseases, and they
      are emerging as promising oncological targets. CONCLUSIONS: mitoK channels
      represent novel targets, and mitoK channel modulators represent an exciting tool
      for pharmacological intervention against such pathological conditions.

PMID- 29022503
TI  - The Renal Outer Medullary Potassium Channel (ROMK): An Intriguing Pharmacological
      Target for an Innovative Class of Diuretic Drugs.
AB  - In the last four decades, the several classes of diuretics, currently available
      for clinical use, have been the first line option for the therapy of widespread
      cardiovascular and non-cardiovascular diseases. Diuretic drugs generally exhibit
      an overall favourable risk/benefit balance. However, they are not devoid of side
      effects. In particular, all the classes of diuretics cause alteration of
      potassium homeostasis. In recent years, understanding of the physiological role
      of the renal outer medullary potassium (ROMK) channels, has shown an intriguing
      pharmacological target for developing an innovative class of diuretic agents: the
      ROMK inhibitors. This novel class is expected to promote diuretic activity
      comparable to (or even higher than) that provided by the most effective drugs
      used in clinics (such as furosemide), with limited effects on potassium
      homeostasis. In this review, the physio-pharmacological roles of ROMK channels in
      the renal function are reported, along with the most representative molecules
      which have been currently developed as ROMK inhibitors.

PMID- 29022504
TI  - Endothelial and circulating progenitor cells in hematological diseases and
      allogeneic hematopoietic stem cell transplantation.
AB  - BACKGROUND: Circulating endothelial cells (CECs), originated form endothelial
      progenitors (EPCs) are mature cells which are not associated with vessel walls,
      and that are detached from the endothelium. Normally, they are present in
      insignificant amounts in the peripheral blood of healthy individuals. On the
      other hand, elevated CECs and EPCs levels have been reported in the peripheral
      blood of patients with different types of cancers and some other diseases.
      Consequently, CECs and EPCs represent a potential biomarker in several clinical
      conditions involving endothelial turnover and remodeling, such as hematological
      diseases. These cells may be involved in disease progression and the neoplastic
      angiogenesis process. Moreover, CESs and EPCs are probably involved in
      endothelial damage that is a marker of several complications following allogeneic
      hematopoietic stem cell transplantation. This review aims to provide an overview
      on the characterization of CECs and EPCs, describe isolation methods and to
      identify the potential role of these cells in hematological diseases and
      hematopoietic stem cell transplantation.

PMID- 29022505
TI  - Pharmacological Targeting of Neuronal Kv7.2/3 Channels: A Focus on Chemotypes and
      Receptor Sites.
AB  - BACKGROUND: The Kv7 (KCNQ) subfamily of voltage-gated potassium channels consists
      of 5 members (Kv7.1-5) each showing characteristic tissue distribution and
      physiological roles. Given their functional heterogeneity, Kv7 channels represent
      important pharmacological targets for the development of new drugs for neuronal,
      cardiovascular and metabolic diseases. OBJECTIVE: In the present manuscript, we
      focus on describing the pharmacological relevance and potential therapeutic
      applications of drugs acting on neuronally-expressed Kv7.2/3 channels, placing
      particular emphasis on the different chemotypes, and highlighting their
      pharmacodynamic and, whenever possible, pharmacokinetic peculiarities. METHODS:
      The present work is based on an in-depth search of the currently available
      scientific literature, and on our own experience and knowledge in the field of
      neuronal Kv7 channel pharmacology. Space limitations impeded to describe the full
      pharmacological potential of Kv7 channels; thus, we have chosen to focus on
      neuronal channels composed of Kv7.2 and Kv7.3 subunits, and to mainly concentrate
      on their involvement in epilepsy. RESULTS: An astonishing heterogeneity in the
      molecular scaffolds exploitable to develop Kv7.2/3 modulators is evident, with
      important structural/functional peculiarities of distinct compound classes.
      CONCLUSION: In the present work we have attempted to show the current status and
      growing potential of the Kv7 pharmacology field. We anticipate a bright future
      for the field, and express our hopes that the efforts herein reviewed will result
      in an improved treatment of hyperexcitability (or any other) diseases.

PMID- 29022506
TI  - Autologous cell therapy for vascular regeneration: the role of proangiogenic
      cells.
AB  - Autologous cell therapy represents a novel treatment option for vascular
      regeneration in different disease conditions. Both experimental and clinical
      studies indicate a therapeutic potential for different proangiogenic cells (PCs),
      including endothelial progenitor cells (EPCs) in the treatment of peripheral
      artery disease. A significant improvement of ischemic symptoms has been reported
      in different trials evaluating PCs for the treatment of critical limb ischemia.
      However, contrasting results from different meta-analyses question the efficacy
      of PC-based approaches on long-term outcomes, including amputation and survival.
      Preclinical studies and clinical trials give support to the safety and
      feasibility of PC therapy in the treatment of ischemic heart disease and heart
      failure, while evidence indicating a benefit on the reduction of cardiovascular
      (CV) events is still uncertain. Clinical studies investigating cell therapy in
      stroke demonstrated controversial results. Despite accumulating experimental
      results support a therapeutic role for PCs in diabetic retinopathy, data from
      randomized clinical trials are lacking. Whether PC therapy may limit vascular
      damage and premature atherosclerosis and reduce CV risk in inflammatory rheumatic
      diseases needs to be investigated. Despite a number of potential clinical
      applications of PCs are emerging, there is evidence that CV risk factors and
      chronic inflammation may induce PC dysfunction, rising possible limitations for
      the efficacy of autologous PC therapy. Thus, novel strategies aimed at improving
      PC viability and angiogenic function are warranted in order to improve the
      efficacy of cell therapy applications.

PMID- 29022507
TI  - Editorial: Relationship Between Cancers and Diseases with Insulin Resistance.

PMID- 29022508
TI  - Editorial: Vascular Protection of Herbal Medicine: Roles and Mechanisms.

PMID- 29022509
TI  - 1,N6-ethenoadenine and other Fluorescent Nucleobase Analogues as Substrates for
      Purine-Nucleoside Phosphorylases: Spectroscopic and Kinetic Studies.
AB  - BACKGROUND: Purine-nucleoside phosphorylase (PNP) is known as a tool for the
      synthesis of various nucleosides and nucleoside analogues. Mechanism, properties,
      molecular diversity and inhibitors of PNP, particularly these of pharmacological
      significance, are briefly characterized. METHODS: UV and fluorescence
      spectroscopy was used for kinetic experiments, and HPLC chromatography for
      product analyses. RESULTS: Applications of various forms of PNP to synthesis of
      selected fluorescent nucleosides, particularly ribosides of 1,N6-ethenoadenine
      and various 8-azapurines (triazolo[4,5-d]pyrimidines) are reviewed. Different
      specificity of various PNP forms is described towards nucleobase and analogue
      substrates as well as variable ribosylation sites observed in some reactions,
      with a possibility to further modify these features via the site-directed
      mutagenesis. CONCLUSION: Present and future applications of the fluorescent or
      fluorogenic ribosides are discussed, with particular emphasis on biochemical and
      clinical analyses with improved sensitivity.

PMID- 29022510
TI  - Whole cell biocatalysts for the preparation of nucleosides and their derivatives.
AB  - : Nucleosides constitute an extensive group of natural and chemically modified
      compounds that display a wide range of structures and activities. Different
      biocatalysts have been developed for their preparation, but the choice of
      commercially available enzymes is limited. Therefore, the search of new
      biocatalysts is particularly attractive. In this sense, microorganisms are a vast
      source of enzymatic diversity that can be directly used as a whole cell
      biocatalysts providing a potential cheaper and suitable route for industrial
      applications. METHODS: This work makes particular emphasis on the following
      methods: the biocatalyzed whole cell synthesis of nucleosides mediated by
      phosphorylases, key biocatalyzed steps involved in other chemoenzymatic routes to
      prepare nucleoside analogues and the transformation of nucleosides in derivatives
      with particular properties. RESULTS: The literature covered in this work confirms
      that biocatalytic procedures that make use of whole cell systems can be
      successfully applied to obtain a wide variety of nucleoside analogues and their
      derivatives, providing alternative and complementary routes to traditional
      chemistry. The direct use of microbial whole cells as biocatalysts affords
      competitive results since it avoids the cumbersome procedures involved in enzyme
      isolation and facilitates multienzymatic processes. These biocatalysts also
      maintain the enzymes in their natural environment, protecting their activities
      from reaction conditions. CONCLUSION: Although the information presented herein
      shows that these methodologies have reached a high degree of development, it is
      expected that future contributions of protein engineering and nucleoside
      metabolism knowledge, among other disciplines, will expand the already wide range
      of applications in nucleoside chemistry of whole cell biocatalysis.

PMID- 29022511
TI  - Metabolism of Nucleosides and Nucleotides Prodrugs.
AB  - BACKGROUND: Modified nucleoside and nucleotide analogs are now the cornerstone of
      antiviral and anticancer chemotherapies. However, these compounds are not active
      on their own and need, after entering the cell, to be metabolized to their active
      5'-triphosphate form. METHOD: Limitations of these metabolic processes led to
      development of nucleoside/nucleotide prodrugs in which nucleosides are masked
      with different groups that can be intracellularly cleaved either chemically or
      enzymatically. RESULTS: Several prodrug approaches have been successfully
      developed in order to increase the efficacy, bioavailability, penetration in
      target organ, and selectivity of nucleoside/nucleotide analogs. CONCLUSION: The
      concept of nucleoside/nucleotide prodrug is now a well-established approach that
      led to the approval of numerous drugs for the treatment of HIV, HBV, HCV, HSV and
      cancer.

PMID- 29022512
TI  - Schistosoma mansoni purine and pyrimidine biosynthesis: structures and kinetic
      experiments in the search for the best therapeutic target.
AB  - BACKGROUND: Schistosoma mansoni is the etiological agent of schistosomiasis, a
      debilitating treatment neglected tropical disease that affects approximately 218
      million people worldwide. Despite its importance, the treatment of
      schistosomiasis relies on a single drug, praziquantel. Some reports on the
      resistance of S. mansoni to this drug have stimulated efforts to develop new
      drugs to treat this disease. S. mansoni possesses all the same pyrimidine
      pathways (de novo, salvage and thymidylate cycles) as those of its host. The
      opposite scenario is true for purine metabolism, in which only the salvage
      pathway is present. These pathways have previously been proposed as potential
      drug targets. RESULTS: Using modern molecular biology techniques, large-scale
      study of these pathways has become possible; 24 genes have been studied, and
      several protein structures and kinetic parameters have been determined. Unique
      characteristics of schistosomal enzymes have been obtained, which show that this
      organism possesses two isoforms of uridine phosphorylase (UP), which share 92% of
      identity. However, only one isoform has a canonical function, whereas the second
      isoform is expressed through all life stages and does not have a known function.
      In addition, the methylthioadenosine phosphorylase (MTAP) is one of the enzymes
      responsible for the previously described adenosine phosphorylase activity, thus
      representing one main difference between S. mansoni and its host. The study of
      adenine phosphoribosyltransferase has revealed possible differential expression
      of the APRT gene in females. This result is consistent with those obtained for
      the experimental treatment of schistosomiasis in monkeys with the adenosine
      analog tubercidin, which eliminates the disease mainly in females. CONCLUSION:
      These important conclusions may aid in the development of new alternative drugs
      to treat schistosomiasis.

PMID- 29022513
TI  - Discrepancies in Animal Models of Preterm Birth.
AB  - BACKGROUND: Preterm birth (PTB) is a multifactorial syndrome occurring before the
      37th week of fullterm pregnancy [1]. Babies delivered preterm experience short
      term and long-term complications affecting multiple organ systems, and serious
      maternal complications include hemorrhage and infection. Each year, an estimated
      15 million babies are born preterm, and complications from prematurity are the
      leading cause of death among children up to 5 years of age [2]. With another
      increase in PTB rates over the last several years, the United States continues to
      have the highest incidence of any industrialized country [3]. Makena (a
      progesterone analog) is the only FDA approved medication available in the United
      States to reduce the risk of PTB. Its use is only indicated in women who are
      currently pregnant with one fetus and have unexpectedly delivered a baby preterm
      in the past [4]. Furthermore, Makena is very expensive and not used in mothers
      with multiple gestations or other risk factors, such as infection, preeclampsia
      and obesity. Consequently, physicians commonly prescribe supportive therapies,
      such as magnesium sulfate, to slow uterine contractions, and glucocorticoids to
      stimulate fetal lung maturity. METHODS: In this article, we review the full
      spectrum of in vivo models that investigators have developed to study PTB,
      including rodent, ruminant and non-human primate models. We evaluate the
      discrepancies among various models, the shortcomings of individual models and how
      well these models reflect various causes of PTB in humans. RESULTS: Recent
      studies reveal that infection is unessential in reproductive disorders linked to
      inflammation, and that infection and inflammation are two of many triggers of PTB
      [1, 5-6]. Despite such findings, many investigators continue recycling infectious
      (using bacterium) and non-infectious-based models (using products of bacteria or
      individual cytokines). These models are inconsistent across laboratories, and
      produce variable degrees of maternal morbidity (inconsistent with human PTB).
      CONCLUSION: The aim of this review is to encourage the reproductive science
      community to rethink the design of non-infectious PTB animal studies. While these
      models have strengthened our understanding of the mediators and triggers of PTB,
      we must develop improved models that are more consistent with the various factors
      associated with human PTB (Fig. 1). If we continue viewing PTB through one lens
      or dimension, Makena will remain the only FDA approved medication. In vivo PTB
      research requires multi-model, multifactorial approaches that account for the
      complexity of living animals within and between species.

PMID- 29022514
TI  - Editorial: Astrocyte-Targeted Therapeutic Strategies for Neurological Disorders.

PMID- 29022515
TI  - Immunopharmacological Activity of Betulin in Inflammation-associated
      Carcinogenesis.
AB  - This review highlights the multiple properties of the birch bark-derived
      pentacyclic triterpene betulin with special focus on its pharmacological activity
      in cancer and inflammation. While less well characterized compared to its
      hydrophilic derivative, betulinic acid, it exhibits potent anticancer activity
      described in many publications. Indeed, underinvestigated are its
      immunomodulatory functions in inflammatory diseases that appeared to enhance
      innate immune cell activities in an adjuvant-like fashion towards an interleukin
      12 driven antitumor immunity. Herein, we like to emphasize the simultaneous and
      dual function of betulin on the basis of recent investigations of the tumor
      microenvironment and enlighten the potential use of betulin in the control of
      inflammation-associated carcinogenesis.

PMID- 29022516
TI  - Folk-Economic Beliefs: An Evolutionary Cognitive Model.
AB  - The domain of "folk-economics" consists in explicit beliefs about the economy
      held by laypeople, untrained in economics, about such topics as e.g., the causes
      of the wealth of nations, the benefits or drawbacks of markets and international
      trade, the effects of regulation, the origins of inequality, the connection
      between work and wages, the economic consequences of immigration, or the possible
      causes of unemployment. These beliefs are crucial in forming people's political
      beliefs, and in shaping their reception of different policies. Yet, they often
      conflict with elementary principles of economic theory and are often described as
      the consequences of ignorance, irrationality or specific biases. As we will
      argue, these past perspectives fail to predict the particular contents of popular
      folk-economic beliefs and, as a result, there is no systematic study of the
      cognitive factors involved in their emergence and cultural success. Here we
      propose that the cultural success of particular beliefs about the economy is
      predictable if we consider the influence of specialized, largely automatic
      inference systems that evolved as adaptations to ancestral human small-scale
      sociality. These systems, for which there is independent evidence, include free
      rider detection, fairness-based partner-choice, ownership intuitions, coalitional
      psychology, and more. Information about modern mass-market conditions activates
      these specific inference-systems, resulting in particular intuitions, e.g., that
      impersonal transactions are dangerous or that international trade is a zero-sum
      game. These intuitions in turn make specific policy proposals more likely than
      others to become intuitively compelling, and as a consequence exert a crucial
      influence on political choices.

PMID- 29022518
TI  - Research on a 'drug-centred' approach to psychiatric drug treatment: assessing
      the impact of mental and behavioural alterations produced by psychiatric drugs.
AB  - AIMS: This article explores an alternative understanding of how psychiatric drugs
      work that is referred to as the drug-centred model of drug action. Unlike the
      current disease-centred model, which suggests that psychiatric drugs work by
      correcting an underlying brain abnormality, the drug-centred model emphasises how
      psychiatric drugs affect mental states and behaviour by modifying normal brain
      processes. The alterations produced may impact on the emotional and behavioural
      problems that constitute the symptoms of mental disorders. METHODS: Arguments are
      put forward that justify the consideration of the drug-centred model. The
      research necessary to support the prescription of drugs according to such a model
      is explored. RESULTS: Evidence from neurochemistry and comparative drug trials do
      not confirm the disease-centred model of drug action. Since psychiatric drugs are
      recognised to have mind- and behaviour-altering properties, the drug-centred
      model constitutes a plausible alternative. The drug-centred model suggests that
      research is needed to identify all the alterations produced by various sorts of
      drugs, both acute and long term, and how these might interact with the symptoms
      and problems associated with different mental disorders. This requires detailed
      animal and volunteer studies and data from patients prescribed drug treatment
      long term, along with placebo-controlled and comparative trials that look at the
      overall impact of drug-induced alterations on well-being and functioning as well
      as symptoms. Research is also needed on alternative ways of fulfilling the
      function of drug treatment. The moral aspect of using drugs to modify behaviour
      rather than treat disease needs honest and transparent consideration.
      CONCLUSIONS: It is hoped this discussion will encourage the psychiatric and
      pharmaceutical research community to provide more of the information that is
      required to use psychiatric drugs safely and effectively.

PMID- 29022517
TI  - Do contamination of and exposure to chicken meat and water drive the temporal
      dynamics of Campylobacter cases?
AB  - Campylobacteriosis, the most frequent bacterial enteric disease, shows a clear
      yet unexplained seasonality. The study purpose was to explore the influence of
      seasonal fluctuation in the contamination of and in the behaviour exposures to
      two important sources of Campylobacter on the seasonality of campylobacteriosis.
      Time series analyses were applied to data collected through an integrated
      surveillance system in Canada in 2005-2010. Data included sporadic, domestically
      acquired cases of Campylobacter jejuni infection, contamination of retail chicken
      meat and of surface water by C. jejuni, and exposure to each source through
      barbequing and swimming in natural waters. Seasonal patterns were evident for all
      variables with a peak in summer for human cases and for both exposures, in fall
      for chicken meat contamination, and in late fall for water contamination. Time
      series analyses showed that the observed campylobacteriosis summer peak could
      only be significantly linked to behaviour exposures rather than sources
      contamination (swimming rather than water contamination and barbequing rather
      than chicken meat contamination). The results indicate that the observed summer
      increase in human cases may be more the result of amplification through more
      frequent risky exposures rather than the result of an increase of the
      Campylobacter source contamination.

PMID- 29022519
TI  - Effects of methionine hydroxy analogue supplementation on the expression of
      antioxidant-related genes of acute heat stress-exposed broilers.
AB  - We evaluated the effects of heat stress (HS) and methionine supplementation on
      biological markers of stress and expression of the genes for superoxide dismutase
      (SOD), thioredoxin (TRx), thioredoxin reductase 1 (TRxR1) and methionine
      sulfoxide reductase A (MsrA) in broilers aged 1 to 21 or 22 to 42 days. The
      broilers were divided into two treatments, one with the recommended level of
      methionine supplementation (MS, supplementation of dl-2-hydroxy-4
      methylthiobutanoic acid (dl-HMTBA)) and one without methionine supplementation
      (MD). The animals were maintained at a temperature of thermal comfort or one of
      HS (38 degrees C for 24 h). Mortality was only observed in 42-day-old broilers
      exposed to HS and fed the MD diet, and the rate was 5%. Starter period: we
      observed an interaction effect between diet and temperature on the gene
      expression of TRxR1 and MsrA, and expression of these genes was higher in the HS
      animals that received the MS diet than that in birds with the MD diet. Grower
      period: the expression of SOD, TRxR1 and MsrA genes, activities of aspartate
      aminotransferase (AST) and creatine kinase (CK) and content of creatinine were
      influenced by both study variables. In the HS animals, the expression of these
      genes, AST activity and creatinine content increased and CK activity decreased.
      In the animals on the MD diet, the expression of these genes and AST and
      creatinine values were higher and the CK activity was lower than those for the
      birds on the MS diet. Our results indicated that under HS conditions, the
      supplementation with dl-HMTBA could mitigate major damage caused by stress
      through the action on some genes related to TRx complex activity.

PMID- 29022520
TI  - Prevalence of suicidal behaviour and associated factors in a large sample of
      Chinese adolescents.
AB  - AIMS: Suicidal behaviour is prevalent among adolescents and is a significant
      predictor of future suicide attempts (SAs) and suicide death. Data on the
      prevalence and epidemiological characteristics of suicidal behaviour in Chinese
      adolescents are limited. This study was aimed to examine the prevalence,
      characteristics and risk factors of suicidal behaviour, including suicidal
      thought (ST), suicide plan (SP) and SA, in a large sample of Chinese adolescents.
      METHOD: This report represents the first wave data of an ongoing longitudinal
      study, Shandong Adolescent Behavior and Health Cohort. Participants included 11
      831 adolescent students from three counties of Shandong, China. The mean age of
      participants was 15.0 (s.d. = 1.5) and 51% were boys. In November-December 2015,
      participants completed a structured adolescent health questionnaire, including
      ST, SP and SA, characteristics of most recent SA, demographics, substance use,
      hopelessness, impulsivity and internalising and externalising behavioural
      problems. RESULTS: The lifetime and last-year prevalence rates were 17.6 and
      10.7% for ST in males, 23.5 and 14.7% for ST in females, 8.9 and 2.9% for SP in
      males, 10.7 and 3.8% for SP in females, 3.4 and 1.3% for SA in males, and 4.6 and
      1.8% for SA in females, respectively. The mean age of first SA was 12-13 years.
      Stabbing/cutting was the most common method to attempt suicide. Approximately 24%
      of male attempters and 16% of female attempters were medically treated. More than
      70% of attempters had no preparatory action. Female gender, smoking, drinking,
      internalising and externalising problems, hopelessness, suicidal history of
      friends and acquaintances, poor family economic status and poor parental
      relationship were all significantly associated with increased risk of suicidal
      behaviour. CONCLUSIONS: Suicidal behaviour in Chinese adolescents is prevalent
      but less than that previously reported in Western peers. While females are more
      likely to attempt suicide, males are more likely to use lethal methods. Multiple
      child and family factors are associated with suicidal behaviour. These findings
      highlight the importance of early screening and intervention of suicidal
      behaviour in Chinese adolescents.

PMID- 29022521
TI  - A stochastic bio-economic pig farm model to assess the impact of innovations on
      farm performance.
AB  - Recently developed innovations may improve the economic and environmental
      sustainability of pig production systems. Generic models are needed to assess the
      impact of innovations on farm performance. Here we developed a stochastic bio
      economic farm model for a typical farrow-to-finish pig farm to assess the impact
      of innovations on private and social profits. The model accounts for emissions of
      greenhouse gases from feed production and manure by using the shadow price of
      CO2, and for stochasticity of economic and biological parameters. The model was
      applied to assess the impact of using locally produced alternative feed sources
      (i.e. co-products) in the diets of finishing pigs on private and social profits
      of a typical Brazilian farrow-to-finish pig farm. Three cases were defined: a
      reference case (with a standard corn-soybean meal-based finishing diet), a
      macauba case (with a macauba kernel cake-based finishing diet) and a co-products
      case (with a co-products-based finishing diet). Pigs were assumed to be fed to
      equal net energy intakes in the three cases. Social profits are 34% to 38% lower
      than private profits in the three cases. Private and social profits are about 11%
      and 14% higher for the macauba case than the reference case, whereas they are 3%
      and 7% lower for the co-products case, respectively. Environmental costs are
      higher under the alternative cases than the reference case suggesting that other
      benefits (e.g. costs and land use) should be considered to utilize co-products.
      The CV of farm profits is between 75% and 87% in the three cases following from
      the volatility of prices over time and variations in biological parameters
      between fattening pigs.

PMID- 29022522
TI  - An approach to anaemia diagnosis - concerns in primary care.

PMID- 29022523
TI  - 'Best buys' for surgery in South Africa.
AB  - Improving access to basic surgical interventions has great potential to improve
      the length and quality of life of many people in low- and middle-income countries
      (LMICs). However, research has shown that current access to surgical
      interventions is limited, and initiatives such as the Lancet Commission on Global
      Surgery 2030 advocate for improved access to basic surgical interventions for
      all. As the needs, health system context and available budgets in each country
      will be different, a critical component of effective local scale-up of surgical
      interventions will be to use tools and processes of health technology assessment
      (HTA). HTA has traditionally been used in high-income countries to make decisions
      about which medicines and devices should be available in a health system, but its
      central concepts, such as assessing clinical effectiveness, cost-effectiveness
      and feasibility, appraising all available evidence, and incorporating wider
      health systems objectives in decision-making, can be applied to decisons about
      how LMICs can best utilise basic surgical interventions from within available
      resources - in essence, to focus spending on the 'best buys'. As South Africa
      (SA) moves towards National Health Insurance (NHI), HTA functions will be
      strengthened. There is potential for SA to lead the practice of application of
      HTA to decisions about how basic surgical interventions are chosen and
      implemented, contributing to the success and sustainability of NHI in SA and the
      health of people in LMICs worldwide.

PMID- 29022524
TI  - Exploring the barriers to implementing National Health Insurance in South Africa:
      The people's perspective.
AB  - This article explores the challenges of implementing the proposed National Health
      Insurance for South Africa (SA), based on the six building blocks of the World
      Health Organization Health System Framework. In the context of the current SA
      health system, leadership, finance, workforce, technologies, information and
      service delivery are explored from the perspective of the people at ground level.
      Through considerations such as these, the universal health coverage goals of
      health equity, efficiency, responsiveness and financial risk protection, might be
      realised.

PMID- 29022525
TI  - Evaluating 5 years' NIMART mentoring in South Africa's HIV treatment programme:
      Successes, challenges and future needs.
AB  - Task shifting has enabled South Africa (SA) to rapidly expand its HIV treatment
      programme. This has been achieved by training and mentoring primary-care nurses
      in nurse initiation and management of antiretroviral therapy (NIMART). Five years
      into its clinical mentoring programme, the Foundation for Professional
      Development conducted an evaluation that identified improved knowledge, attitudes
      and confidence perceived by nurses who received NIMART mentoring. Low completion
      rates for the Department of Health (DoH) NIMART training process were identified
      and therefore targeted mentoring was introduced; this increased the percentage of
      primary nurses eligible for DoH certificates of clinical competence in NIMART
      from 12%, adding a further 30%. There remain a large number of primary nurses who
      require mentoring in order to complete the NIMART process. For those who have
      completed the process, there remains a need for ongoing mentoring as SA's HIV
      programme evolves, complex cases emerge and primary care undergoes change.

PMID- 29022526
TI  - Cytomegalovirus retinitis and HIV: Case reviews from KwaZulu-Natal Province,
      South Africa.
AB  - BACKGROUND: Retinal cytomegalovirus (CMV) infection is a common opportunistic
      infection and remains a significant contributor to visual loss in patients with
      AIDS. We highlight the poor outcomes of CMV retinitis in three HIV-infected
      patients who were initiated on antiretroviral therapy (ART). We conducted a
      retrospective chart review of advanced stage HIV-infected patients with known CMV
      retinitis.Case 1. A 37-year-old man, with a CD4+ cell count of 35 cells/uL,
      presented for ART initiation with a 5-month history of visual loss in his left
      eye. Fundoscopy showed left eye CMV retinitis and right eye HIV retinopathy. ART
      and 5 months of weekly intravitreal ganciclovir injections (left eye) were
      commenced. Six-month outcomes included virological suppression, and visual acuity
      in the right eye of 6/6 and in the left eye of 3/60.Case 2. A 31-year-old woman,
      with a CD4+ cell count of 39 cells/uL and on tuberculosis therapy, presented for
      ART initiation. She presented with a 2-month history of decreased visual acuity.
      Fundoscopy showed bilateral CMV retinitis, which was more pronounced in the left
      eye. ART and 8 months of intravitreal ganciclovir injections were commenced. Six
      month outcomes included virological suppression and visual acuity in the right
      eye of 6/9, and in the left eye of 6/24.Case 3. A 29-year-old woman, with a CD4+
      cell count of 24 cells/uL, who was on tuberculosis therapy and ART, complained of
      blurred vision at her 2-month ART follow-up visit. Fundoscopy showed bilateral
      retinal detachment secondary to CMV retinitis. While silicone oil tamponade and
      subsequent retinectomy successfully repaired the right eye, extensive damage
      rendered the left eye irreparable. Six-month outcomes included virological
      suppression, with 6/120 visual acuity in the right eye and complete blindness in
      the left eye. CONCLUSION: CMV retinitis causes debilitating, permanent sequelae,
      which is preventable by ART initiation at higher CD4+ cell counts. Despite
      achieving virological suppression, vision could not be completely restored in
      these patients, irrespective of the severity of CMV retinitis.

PMID- 29022527
TI  - Protection of the human research participant: A structured review.
AB  - The history of health research, and concerns about the protection of human
      participants, dates back as far as the 1800s. The regulation, legislation and
      ethics-review requirements regarding the protection of the human research
      participants cause lively debates among researchers and scientists. The objective
      of this article is to share the findings of a structured review that was aimed at
      investigating the impact of and challenges with regard to the legislation,
      governance and research regulations aimed at protecting human research
      participants. The thematic analysis of the findings revealed dissatisfaction with
      diverse operational practices; different legislation and regulation practices;
      and institutional governance. Simplified and universally agreed-upon regulations
      and operational practices are needed, as is a common understanding of all
      concepts relating to ethical research conduct.

PMID- 29022528
TI  - Diagnostic accuracy of GeneXpert MTB/RIF in musculoskeletal tuberculosis: High
      sensitivity in tissue samples of HIV-infected and HIV-uninfected patients.
AB  - BACKGROUND: GeneXpert MTB/RIF is useful for the diagnosis of pulmonary TB in
      adults, but there is limited evidence on its usefulness in extrapulmonary TB.
      OBJECTIVES: To investigate the diagnostic accuracy of GeneXpert MTB/RIF in HIV
      infected and HIV-uninfected patients with suspected musculoskeletal TB. METHODS:
      A prospective study of patients with suspected musculoskeletal (bone and joint)
      TB was undertaken. The diagnostic accuracy of GeneXpert MTB/RIF was compared with
      the reference standards of culture and histopathology. RESULTS: A total of 206
      biopsies from 201 patients (23% HIV-infected) were evaluated. The sensitivity and
      specificity of GeneXpert MTB/RIF was 92.3% (84/91) and 99.1% (114/115),
      respectively. GeneXpert MTB/RIF detected 8.8% more cases than culture (84/91
      (92.3%) v. 76/91 (83.5%), respectively; p=0.069). GeneXpert MTB/RIF also detected
      all 4 multidrug-resistant TB cases and an additional 2 rifampicin-resistant cases
      in culture-negative samples. The sensitivity of GeneXpert MTB/RIF in HIV-infected
      patients was 96.9% (31/32) v. 89.6% (43/48) in HIV-uninfected patients (p=0.225).
      CONCLUSION: GeneXpert MTB/RIF is an accurate test for the detection of TB in
      tissue samples of HIV-infected and HIV-uninfected patients with suspected
      musculoskeletal TB. A positive GeneXpert MTB/RIF result should be regarded as
      microbiological confirmation of TB.

PMID- 29022529
TI  - Deep-vein thrombosis in the era of high HIV and tuberculosis prevalence: A
      prospective review of its diagnosis and treatment in a quaternary centre.
AB  - BACKGROUND: Venous thromboembolic disease (VTE) is a leading cause of morbidity
      and mortality worldwide. HIV and tuberculosis (TB) infections have an
      aetiological association with VTE. Implementation of national HIV and TB
      programmes in South Africa (SA) has changed the burden of these two conditions,
      with resultant effects on VTE prevalence. Furthermore, with the increased use of
      direct oral anticoagulants (DOACs), baseline thrombosis data are needed to
      evaluate the effect of these new agents. OBJECTIVES: To determine real-life
      baseline VTE characteristics in a pre-DOAC era, and to document the association
      of HIV and TB infections with VTE. METHODS: This was a single-centre prospective
      cohort study performed in a quaternary care centre at Charlotte Maxeke
      Johannesburg Academic Hospital, SA. Key inclusion criteria included signed
      informed consent by adults (>=18 years) with a new episode of thrombosis.
      Procedures included physical examination, thrombosis risk factor assessment,
      duplex Doppler examination, thrombophilia screening, inpatient treatment and
      outpatient follow-up. RESULTS: Ninety-nine participants with confirmed thrombosis
      met the inclusion criteria. Participants were predominantly black (79.8%) and
      female (64.6%), with a median age of 46 (interquartile range (IQR) 38 - 57)
      years. The prevalences of HIV and TB were 53.0% and 21.2%, respectively. The most
      common risk factors for thrombosis were TB (17.2%) and malignancies (14.1%).
      Thrombophilia screening had a low diagnostic yield. The median time to target
      international normalised ratio during hospitalisation was 5.5 (IQR 4.0 - 7.0)
      days and the median duration of hospitalisation was 9 (IQR 7 - 11) days. The
      overall mortality rate in the cohort at 3 months post hospitalisation was 12.1%.
      CONCLUSIONS: This prospective study provides real-life data on thrombosis
      diagnosis and management at a quaternary public healthcare facility, providing a
      valuable baseline against which the effect of new DOAC anticoagulants can be
      assessed. Further research is required to clarify the aetiological association
      between thrombosis and HIV and TB.

PMID- 29022530
TI  - Male involvement in prevention of mother-to-child transmission of HIV in the
      context of partner testing in Goba town, Ethiopia: A facility-based cross
      sectional study.
AB  - BACKGROUND: Antenatal care (ANC) is an entry point for the prevention of mother
      to-child transmission (PMTCT), particularly when a man accompanies his spouse for
      voluntary counselling and testing (VCT), even though this seldom happens in
      Ethiopia. OBJECTIVE: To study the role of male partners in improving PMTCT/ANC,
      which is essential to prevent HIV/AIDS transmission in this country. Our study
      focused on identifying barriers for the low involvement in PMTCT/ANC among male
      partners whose spouses received ANC. METHODS: A total of 422 male partners in
      Goba town, Oromia regional state, Ethiopia, were recruited in September - October
      2014 and enrolled by a systematic sampling method. A facility-based cross
      sectional study and two focus group discussions (FGDs) were conducted. Binary
      logistic regression and odds ratios were calculated to ascertain sociodemographic
      and other important information compared with the outcome variable and PMTCT/ANC,
      while the findings of the FGDs were grouped according to the emerging themes and
      analysed manually by means of a thematic approach. RESULTS: The percentage of
      male partners (22.7%) accompanying their spouses for HIV testing and counselling
      at antenatal clinics improved three-fold when an invitation letter was introduced
      as a new initiative to increase male participation. Individuals in the age group
      15 - 29 years (adjusted odds ratio (AOR) 5.4, 95% confidence interval (CI) 1.66 -
      17.85), and whose duration of marriage was ?5 years (AOR 5.6, 95% CI 1.83 -
      17.30), were more likely to be tested than their referent groups. Men without a
      higher education (AOR 0.1, 95% CI 0.02 - 0.50), who disagreed with legal
      enforcement (AOR 0.1, 95% CI 0.07 - 0.32), were less likely to be tested, while
      those who did not notify their partners (AOR 8.4, 95% CI 1.92 - 37.12) were more
      likely to use the service. Being busy, proxy testing, fears of testing HIV
      positive, neglecting the importance of VCT, and inadequate knowledge about the
      PMTCT/ANC programme were other barriers that came to the fore in the FGDs.
      CONCLUSION: Identified barriers have to be addressed, and helpful practices, such
      as using invitation letters to increase the uptake of the service by male
      partners, have to be instituted.

PMID- 29022531
TI  - Survival of patients with Kaposi's sarcoma in the South African antiretroviral
      treatment era: A retrospective cohort study.
AB  - BACKGROUND: When South Africa (SA) implemented its antiretroviral therapy (ART)
      programme in 2004, the model for treating HIV-positive Kaposi's sarcoma (KS)
      patients shifted from symptomatic palliation to potential cure. OBJECTIVE: To
      evaluate survival and changes over time in AIDS-KS patients treated at a tertiary
      academic hospital oncology unit (the Steve Biko Academic Hospital medical
      oncology unit) in Pretoria, SA, in the context of ART availability in SA.
      METHODS: We conducted a retrospective review of electronic and paper records of
      KS patients who accessed cancer care between May 2004 and September 2012. We used
      Kaplan-Meier survival functions to estimate 1- and 2-year survival, and Cox
      regression models to identify changes over time and prognostic factors. RESULTS:
      Our study included 357 AIDS-KS patients, almost all of whom were black Africans
      (n=353, 98.9%); 224 (62.7%) were men. The median age at cancer diagnosis was 37
      (interquartile range (IQR) 30 - 43) years, and the median baseline CD4+ count was
      242 (IQR 130 - 403) cells/uL. Most patients received ART (n=332, 93.0%) before or
      after KS diagnosis; 169 (47.3%) were treated with chemotherapy and 209 (58.6%)
      with radiation therapy. Mortality was 62.7% lower (adjusted hazard ratio (HR)
      0.37, 95% confidence interval (CI) 0.19 - 0.73) in the late (2009 - 2012) than in
      the early (2004 - 2008) ART period. Receiving chemotherapy (adjusted HR 0.3, 95%
      CI 0.15 - 0.61) and poor-risk AIDS Clinical Trials Group KS stage (adjusted HR
      2.88, 95% CI 1.36 - 6.09) predicted mortality. CONCLUSIONS: Our results show that
      large national ART roll-out programmes can successfully reduce KS-related
      mortality at the individual patient level. If ART coverage is extended, KS
      associated morbidity and mortality are likely to drop.

PMID- 29022532
TI  - HIV-positive patients in the intensive care unit: A retrospective audit.
AB  - BACKGROUND: The indications for and outcomes of intensive care unit (ICU)
      admission of HIV-positive patients in resource-poor settings such as sub-Saharan
      Africa are unknown. OBJECTIVE: To identify indications for ICU admission and
      determine factors associated with high ICU and hospital mortality in HIV-positive
      patients. METHODS: We reviewed case records of HIV-positive patients admitted to
      the medical and surgical ICUs at Groote Schuur Hospital, Cape Town, South Africa,
      from 1 January 2012 to 31 December 2012. RESULTS: Seventy-seven HIV-positive
      patients were admitted to an ICU, of whom two were aged <18 years and were
      excluded from the final analysis. HIV infection was newly diagnosed in 37.3% of
      the patients admitted during the study period. HIV-positive patients had a median
      CD4 count of 232.5 (interquartile range 59 - 459) cells/uL. Respiratory illness,
      mainly community-acquired pneumonia, accounted for 30.7% of ICU admissions. ICU
      and hospital mortality rates were 25.3% and 34.7%, respectively. Predictors of
      ICU mortality included an Acute Physiology and Chronic Health Evaluation IotaIota
      (APACHE II) score >13 (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.1 -
      1.7; p=0.015), receipt of renal replacement therapy (RRT) (OR 2.2, 95% CI 1.2 -
      4.1; p=0.018) and receipt of inotropes (OR 2.3, 95% CI 1.6 - 3.4; p<0.001).
      Predictors of hospital mortality were severe sepsis on admission (OR 2.8, 95% CI
      0.9 - 9.1; p=0.07), receipt of RRT (OR 1.9, 95% CI 1.0 - 3.6; p=0.056) and
      receipt of inotropic support (OR 2.0, 95% CI 1.4 - 3.2; p<0.001). Use of highly
      active antiretroviral therapy (HAART), CD4 count, detectable HIV viral load and
      diagnosis at ICU admission did not predict ICU or hospital mortality.
      CONCLUSIONS: Respiratory illnesses remain the main indication for ICU in HIV
      positive patients. HIV infection is often diagnosed late, with patients
      presenting with life-threatening illnesses. Severity of illness as indicated by a
      high APACHE IotaIota score, multiple organ dysfunction requiring inotropic
      support and RRT, rather than receipt of HAART, CD4 count and diagnosis at ICU
      admission, are predictors of ICU and hospital mortality.

PMID- 29022533
TI  - Distribution of hepatitis B virus infection in Namibia.
AB  - BACKGROUND: Namibia regards hepatitis B virus (HBV) infection as a public health
      problem and introduced hepatitis B vaccinations for infants during 2009. However,
      information on HBV infection in the country remains limited, and effective public
      health interventions may be compromised in the absence of adequate evidence-based
      data. Available data from the World Health Organization (WHO) estimate that 15 -
      60% of the normal population in many African countries may be positive for one or
      more of the HBV serological markers. OBJECTIVE: To investigate the distribution
      of HBV infection in Namibia, using available laboratory data for 2013. METHODS: A
      cross-sectional descriptive study was conducted using pre-existing electronic
      laboratory data on HBV infection. The data were retrieved from the central
      Namibia Institute of Pathology laboratory in Windhoek during January - December
      2013. Tests were done on the following three main groups: (i) pregnant women
      during routine antenatal care (ANC) visits; (ii) patients with HIV/AIDS during
      antiretroviral therapy clinic visits; and (iii) any other individual suspected of
      having HBV infection. RESULTS: Of a total of 77 238 hepatitis B surface antigen
      test results retrieved countrywide, 9 087 (11.8%) were positive. Of the positive
      results, 246/9 087 (2.7%) were in children aged 0 - 14 years, with the sexes
      equally affected. HBV infections increased markedly, particularly among females,
      in the age group 15 - 39 years, reaching a peak in the age group 30 - 34 years.
      Routine screening of pregnant women for HBV during ANC visits was found to be
      systematically conducted in only two regions, Ohangwena and Khomas. CONCLUSIONS:
      This study showed high proportions of positive results in pregnant women,
      patients with HIV/AIDS and individuals suspected of having HBV infection. The
      Ministry of Health and Social Services and stakeholders may wish to consider
      improving the routine and surveillance reporting systems for viral hepatitis and
      uptake of screening for pregnant women in all regions, and expanding HBV
      screening to other population groups. Population-based or similar studies are
      therefore required to determine the HBV prevalence and risk factors. This will
      assist Namibia in developing appropriate national viral hepatitis strategies as
      per WHO recommendations.

PMID- 29022534
TI  - Therapeutic drug monitoring of amlodipine and the Z-FHL/HHL ratio: Adherence
      tools in patients referred for apparent treatment-resistant hypertension.
AB  - BACKGROUND: Non-adherence to antihypertensives is a cause of 'pseudo-treatment
      resistant' hypertension. OBJECTIVE: To determine whether monitoring plasma
      amlodipine concentrations and inhibition of angiotensin-converting enzyme (ACE)
      can be adjunct adherence tools. METHODS: Patients with hypertension who were
      prescribed enalapril and amlodipine were enrolled. Blood pressures (BPs) were
      monitored and an adherence questionnaire was completed. Steady-state amlodipine
      was assayed using liquid chromatography-mass spectrometry and degree of ACE
      inhibition using the Z-FHL/HHL (z-phenylalanine-histidine-leucine/hippuryl
      histidine-leucine) ratio. RESULTS: One hundred patients (mean (standard
      deviation) age 50.5 (12) years, 46% male) were enrolled. Based on plasma assays,
      26/97 patients (26.8%) were unsuppressed by enalapril and 20/100 (20%) were sub
      therapeutic for amlodipine. There were significant BP differences based on plasma
      levels of the medication: 21/20 mmHg lower in the group with suppressed ACE and
      26/20 mmHg in the group with steady-state amlodipine concentrations. CONCLUSIONS:
      Monitoring antihypertensive adherence by assaying plasma medication
      concentrations is a feasible option for evaluating true v. pseudo-resistant
      hypertension.

PMID- 29022535
TI  - Gender disparities in pulmonary hypertension at a tertiary centre in Cameroon.
AB  - BACKGROUND: Pulmonary hypertension (PH) is a potent cause of heart failure and
      has been little investigated in the African setting. OBJECTIVE: To investigate
      the effects of gender on the clinical presentation, echocardiographic features
      and outcomes of patients with PH in Douala, Cameroon. METHODS: A prospective
      cohort study was conducted from March 2012 to December 2013 as part of the Pan
      African Pulmonary Hypertension Cohort study. PH was diagnosed by echocardiography
      and defined as a right ventricular systolic pressure >35 mmHg in the absence of
      acute right heart failure. Patients were followed up for a maximum of 12 months
      for primary endpoint mortality. RESULTS: In total, 130 patients with PH were
      recruited; 71 (54.6%) were women. The median age was 59.2 years for men and 58.3
      years for women (p=0.76). Active smoking and alcohol use were more frequent in
      men than women (both p<0.001), but women had greater exposure to indoor cooking
      fumes than men (p<0.001). Previous tuberculosis infection (11.3% v. 1.7%) and S3
      gallop rhythm (30.9% v. 11.9%) were more common in women (both p<0.03). Women had
      a significantly higher mean systolic blood pressure (134 mmHg v. 125 mmHg;
      p=0.04) and pulse pressure (53.8 mmHg v. 44.9 mmHg; p=0.01) and a lower mean
      haemoglobin concentration (10.4 g/dL v. 12.4 g/dL; p<0.05) compared with men.
      Echocardiographic left ventricular (LV) systolic dysfunction was more frequent in
      men: mean LV ejection fraction 42.6% v. 51.5% (p=0.01) and mean fractional
      shortening 21.4% v. 28.6% (p=0.01). The overall mortality rate was 20.3%, and
      rates were similar in the two groups (Kaplan-Meier log rank 1.1; p=0.30).
      CONCLUSIONS: Despite differences in baseline characteristics including
      cardiovascular risk factors, mortality rates on follow-up were similar in men and
      women in this study. However, these different baseline characteristics probably
      suggest differences in the pathogenesis of PH in men and women in our setting
      that need further investigation.

PMID- 29022536
TI  - Short-term outcomes of inborn v. outborn very-low-birth-weight neonates (<1 500
      g) in the neonatal nursery at Groote Schuur Hospital, Cape Town, South Africa.
AB  - BACKGROUND: The Groote Schuur Hospital (GSH) neonatal nursery provides level 3
      care for the Metro West Health District in the Western Cape Province of South
      Africa. Worldwide, very-low-birth-weight (VLBW) neonates delivered in level 3
      neonatal units have better outcomes than those transported from other facilities.
      OBJECTIVES: To identify the characteristics and outcomes of VLBW neonates at GSH,
      with emphasis on differences between inborns and outborns. METHODS: This was a
      retrospective cohort study. VLBW neonates admitted to the GSH neonatal nursery
      between 1 January 2012 and 31 December 2013 were enrolled on the Vermont Oxford
      Network database and reviewed. RESULTS: Of 1 032 VLBW neonates enrolled, 906
      (87.8%) were delivered at GSH and 126 (12.2%) were outborn. Access to antenatal
      care, antenatal steroids and inborn status were statistically significant
      predictors of mortality and survival without morbidity. The mothers of inborn
      patients were more likely than those of outborn patients to have received
      antenatal care (89.1% v. 57.9%; p<0.0001) and antenatal steroids (64.2% v. 15.2%;
      p<0.0001). Inborns required less ventilatory support (16.2% v. 57.9%; p<0.0001)
      and surfactant administration than outborns (25.3% v. 65.1%; p<0.0001), and
      developed less late infection (8.8% v. 23.4%; p<0.0001), severe intraventricular
      haemorrhage (3.7% v. 13.9%; p<0.0001) and chronic lung disease (5.3% v. 13.4%;
      p=0.003). The incidence of necrotising enterocolitis was similar in the two
      groups (5.9% v. 8.7%; p=0.227). The mortality rate was 18.4% for inborns and
      33.3% for outborns (p<0.0001). Mortality declined as birth weight increased. Of
      the survivors, 85.0% of inborns and 70.2% of outborns did not develop serious
      morbidity (p=0.003). CONCLUSIONS: VLBW neonates delivered at GSH had better
      outcomes than their outborn counterparts. Perinatal regionalisation is beneficial
      to our patients, with antenatal care, timeous transfer in utero and antenatal
      steroids contributing to excellent outcomes.

PMID- 29022537
TI  - Respiratory comorbidity in South African children with atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is an early and important step in the
      propagation of the allergic march, enhancing food and respiratory allergies via
      epicutaneous sensitisation to allergens. OBJECTIVES: To determine the prevalence
      and patterns of aeroallergen sensitisation, asthma and allergic rhinitis in South
      African (SA) children with AD. METHODS: This was a prospective, observational
      study in a paediatric university hospital in Cape Town, SA. Children with
      moderate to severe AD, aged 6 months - 10 years, were recruited randomly and
      investigated for food sensitisation and allergy. They were assessed for
      sensitisation to aeroallergens by the immuno solid-phase allergen chip test.
      House-dust mite DerP and DerF, dust mite Eur m, Timothy grass, Bermuda grass,
      tree pollen, mould (Alternaria), cat and dog sensitisation patterns were
      analysed. Symptoms of asthma and allergic rhinitis were elicited using a
      questionnaire modified from the International Study of Asthma and Allergies in
      Childhood study questions. RESULTS: One hundred participants (59 black Africans
      and 41 of mixed ethnicity) were enrolled (median age 42 months). Of the
      participants, 39% had symptoms of asthma and 53% symptoms of allergic rhinitis;
      89% tested positive to at least one aeroallergen, most commonly house-dust mite
      DerP or DerF (81%), dust mite Eur m (51%), Timothy grass (36%) and cat (35%).
      Asthma, allergic rhinitis and aeroallergen sensitisation all increased with
      increasing age, while food allergy decreased with age. Food allergy was not an
      independent risk factor for respiratory allergies. Children were sensitised to
      indoor allergens (house-dust mite, pets) from an early age, while pollen
      allergies increased with age. CONCLUSIONS: In this cohort of SA children with
      moderate to severe AD, comorbidity with respiratory allergies was high. The
      prevalence of respiratory allergies increased with age while food allergy
      decreased with age, in keeping with the pattern of the allergic march. Seasonal
      allergies increased with age, while house-dust mite and pet allergy peaked in
      younger children, in keeping with early exposure via a defective skin barrier.
      Early and effective restoration of the skin barrier in AD may be a target for
      reducing aeroallergen-related diseases.

PMID- 29022538
TI  - Preoperative fasting times: Prescribed and actual fasting times at Universitas
      Hospital Annex, Bloemfontein, South Africa.
AB  - BACKGROUND: Guidelines recommend a preoperative fasting period of 6 hours for
      solid food and 2 hours for clear fluids. Because of fixed meal times and
      imprecise operation starting times, patients often fast for an extended period of
      time. OBJECTIVE: To investigate the prescribed preoperative fasting times, and
      the actual duration of fasting, compared with the internationally accepted
      fasting times for solid food and clear fluids. METHODS: Patients (N=105) aged 14 
      60 years, who were scheduled for elective surgery in the morning session (list
      starting time 07h00), were included in this prospective study. On arrival in
      theatre, all patients were asked when they last ate and drank. Anaesthetic
      records were used to determine the prescribed fasting times and operation
      starting times. RESULTS: For solids, patients were most frequently prescribed to
      start fasting from 22h00 to 00h00 (53.3% and 39.1%, respectively). No patient
      fasted <8 hours. The median duration of fasting was 14 hours and 45 minutes
      (range 9 hours and 45 minutes - 19 hours and 5 minutes). For fluids, patients
      were most frequently prescribed to start fasting from 05h00 (46.7%), 00h00
      (27.6%) and 22h00 (7.6%). In practice, no patient ingested fluids after 22h30 or
      <9 hours preoperatively. The median fasting time for oral fluids was 13 hours and
      25 minutes (range 9 hours and 37 minutes - 19 hours and 5 minutes). CONCLUSION:
      Most patients started fasting too early preoperatively, consequently withholding
      food and oral fluids for longer than recommended. An increased awareness
      regarding complications of unnecessarily long fasting times, and interventions to
      correct this problem, is required.

PMID- 29022539
TI  - Bibliometric trends of South African environmental health articles between 1998
      and 2015: Making local research visible and retrievable.
AB  - BACKGROUND: South Africa (SA) has to grapple with multiple burdens of disease for
      which environmental factors have a role to play in both causation and prevention.
      This article describes a bibliometric review of environmental health indexed
      literature for SA over an 18-year period. OBJECTIVES: To provide an overview of
      the nature of SA-based published environmental health indexed research and to
      identify search challenges, frequently researched topics, and gaps and
      opportunities for future research. METHODS: The Web of Science, PubMed and
      Science Direct were used to search for original, peer-reviewed and review
      articles with the inclusion criteria 'environmental health' and 'South Africa'
      available online and published between 1998 and 2015, inclusively. RESULTS: A
      total of 230 journal articles were included in the bibliometric analysis. The
      highest number of articles (n=54) was published in 2015. The majority of the
      first authors were affiliated with SA institutions (n=160, 69.5%). For the
      articles where funding was explicitly declared (n=148), the three most frequently
      occurring agencies that funded the published research were the National Research
      Foundation in SA (n=17), the South African Medical Research Council (n=13) and
      the Water Research Commission (n=9). There was little inter-annual/environmental
      health category variation over time owing to the relatively small sample size.
      The largest number of retrieved journal articles was in the area of environmental
      pollution control (n=76), followed by environmental health lifestyle and
      behaviour-related topics (n=42) and then water monitoring (n=26). CONCLUSIONS:
      Despite the research needed to solve large environmental health challenges in SA,
      environmental health was only used as a keyword in title, author keywords or
      abstract for 230 SA-based studies over an 18-year period. This makes it extremely
      difficult for environmental health research to be located and used to inform the
      profession as well as the research agenda. Several issues that environmental
      health practitioners are typically tasked to implement and monitor are not
      indexed as environmental health topics. The need for authors to use
      'environmental health' as a keyword is emphasised, particularly if research is to
      inform decision-making and policy support, as well as guide future research in
      the country.

PMID- 29022540
TI  - Notification that new names of prokaryotes, new combinations, and new taxonomic
      opinions have appeared in volume 67, part 7, of the IJSEM.

PMID- 29022541
TI  - Ruegeria profundi sp. nov. and Ruegeria marisrubri sp. nov., isolated from the
      brine-seawater interface at Erba Deep in the Red Sea.
AB  - Two moderately halophilic marine bacterial strains of the family
      Rhodobacteraceae, designated ZGT108T and ZGT118T, were isolated from the brine
      seawater interface at Erba Deep in the Red Sea (Saudi Arabia). Cells of both
      strains were aerobic, rod-shaped, non-motile, and Gram-stain-negative. The
      sequence similarity of the 16S rRNA genes of strains ZGT108T and ZGT118T was 94.9
      %. The highest 16S rRNA gene sequence similarity of strain ZGT108T to its closest
      relative, Ruegeria conchae JCM 17315T, was 98.9 %, while the 16S rRNA gene of
      ZGT118T was most closely related to that of Ruegeria intermedia LMG 25539T (97.7
      % similarity). The sizes of the draft genomes as presented here are 4 258 055 bp
      (strain ZGT108T) and 4 012 109 bp (strain ZGT118T), and the G+C contents of the
      draft genomes are 56.68 mol% (ZGT108T) and 62.94 mol% (ZGT108T). The combined
      physiological, biochemical, phylogenetic and genotypic data supported placement
      of both strains in the genus Ruegeria and indicated that the two strains are
      distinct from each other as well as from all other members in the genus Ruegeria.
      This was also confirmed by low DNA-DNA hybridization values (<43.6 %) and low ANI
      values (<91.8 %) between both strains and the most closely related Ruegeria
      species. Therefore, we propose two novel species in the genus Ruegeria to
      accommodate these novel isolates: Ruegeriaprofundi sp. nov. (type strain
      ZGT108T=JCM 19518T=ACCC 19861T) and Ruegeriamarisrubri sp. nov. (type strain
      ZGT118T=JCM 19519T=ACCC 19862T).

PMID- 29022542
TI  - Streptococcus azizii sp. nov., isolated from naive weanling mice.
AB  - Three isolates of a previously reported novel catalase-negative, Gram-stain
      positive, coccoid, alpha-haemolytic, Streptococcus species that were associated
      with meningoencephalitis in naive weanling mice were further evaluated to confirm
      their taxonomic status and to determine additional phenotypic and molecular
      characteristics. Comparative 16S rRNA gene sequence analysis showed nearly
      identical intra-species sequence similarity (>=99.9 %), and revealed the closest
      phylogenetically related species, Streptococcus acidominimus and
      Streptococcuscuniculi, with 97.0 and 97.5 % sequence similarity, respectively.
      The rpoB, sodA and recN genes were identical for the three isolates and were
      87.6, 85.7 and 82.5 % similar to S. acidominimus and 89.7, 86.2 and 80.7 %
      similar to S. cuniculi, respectively. In silico DNA-DNA hybridization analyses of
      mouse isolate 12-5202T against S. acidominimus CCUG 27296T and S. cuniculi CCUG
      65085T produced estimated values of 26.4 and 25.7 % relatedness, and the
      calculated average nucleotide identity values were 81.9 and 81.7, respectively.
      These data confirm the taxonomic status of 12-5202T as a distinct Streptococcus
      species, and we formally propose the type strain, Streptococcusazizii 12-5202T
      (=CCUG 69378T=DSM 103678T). The genome of Streptococcus azizii sp. nov. 12-5202T
      contains 2062 total genes with a size of 2.34 Mbp, and an average G+C content of
      42.76 mol%.

PMID- 29022543
TI  - Gemmobacter straminiformis sp. nov., isolated from an artificial fountain.
AB  - A Gram-stain-negative, non-motile and facultative anaerobic bacterium, designated
      CAM-8T, was isolated from an artificial fountain at Chonbuk National University,
      South Korea. The novel strain grew at 20-37  degrees C (optimum 25  degrees C),
      pH 5.5-7.0 (optimum 6.0) and with 0-2 % NaCl (optimum 0 %). Oxidase and catalase
      activities were positive. The cell morphology of strain CAM-8T was atypical rods
      0.6-0.8 um in width and 4.5-6.5 um in length, with a peaked tip and sometimes a
      bulb shape. CAM-8T existed as single cells, and as pairs or chains of cells. The
      phylogenetic analysis of 16S rRNA gene sequences indicated that strain CAM-8T
      clustered with Gemmobacter nectariphilus JCM 11959T and Gemmobactermegaterium JCM
      18498T within the genus Gemmobacter. The DNA G+C content of strain CAM-8T was
      65.9 mol%. The respiratory quinone was ubiquinone Q-10. The major fatty acids
      were C18 : 1omega7c and/or C18 : 1omega6c. The polar lipids of strain CAM-8T
      consisted of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine,
      two uncharacterized phospholipids, an uncharacterized aminolipid, an
      uncharacterized glycolipid, an uncharacterized aminophospholipid and four
      uncharacterized lipids. On the basis of phenotypic, phylogenetic and
      chemotaxonomic data, strain CAM-8T (=KACC 19224T=JCM 31905T) is considered to
      represent a novel species of the genus Gemmobacter, for which the name
      Gemmobacter straminiformis sp. nov. is proposed.

PMID- 29022544
TI  - Lymphogranuloma venereum rates increased and Chlamydia trachomatis genotypes
      changed among men who have sex with men in Sweden 2004-2016.
AB  - This study aimed to determine the incidence of lymphogranuloma venereum (LGV) in
      Sweden since 2004 and to study in detail a consecutive number of Chlamydia
      trachomatis cases in men who have sex with men (MSM) during a 10 month period
      (September 2014 to July 2015). LGV increased from sporadic import cases in 2004
      to comprise a spread within Sweden in 2016. Initially, only the L2b ompA genotype
      was detected, but in 2015 half of the genotyped LGV cases were L2 genotype. The
      changing genotype distribution in Sweden is linked to increased LGV spread in
      Europe. High-resolution multilocus sequence typing of 168 C. trachomatis cases
      from MSM in 2015 resulted in 29 sequence types, of which 3 accounted for 49 % of
      cases. The increased rates and different genotypes of LGV indicate that more
      concern for high-risk taking MSM is needed to avoid further spread of this
      invasive infection.

PMID- 29022546
TI  - Erratum: Proposal for the reclassification of obligately purine-fermenting
      bacteria Clostridium acidurici (Barker 1938) and Clostridium purinilyticum (Durre
      et al. 1981) as Gottschalkia acidurici gen. nov. comb. nov. and Gottschalkia
      purinilytica comb. nov. and of Eubacterium angustum (Beuscher and Andreesen 1985)
      as Andreesenia angusta gen. nov. comb. nov. in the family Gottschalkiaceae fam.
      nov.

PMID- 29022545
TI  - Nocardioides litorisoli sp. nov., isolated from lakeside soil.
AB  - A Gram-stain-positive, rod-shaped, non-spore-forming bacterium, designated as x
      2T, was isolated from lakeside soil of Sayram in the Xinjiang Uygur Autonomous
      Region, PR China. On the basis of 16S rRNA gene sequences, strain x-2T belongs to
      the genus Nocardioides in the family Nocardioidaceae, being most closely related
      to Nocardioides panacisoli Gsoil 346T (97.36 % 16S rRNA gene sequence
      similarity). Strain x-2T was characterized chemotaxonomically and found to have
      ll-diaminopimelic acid in the cell-wall peptidoglycan, phosphatidylglycerol,
      diphosphatidylglycerol, glycolipids and another three unknown phospholipids as
      the major polar lipids, MK-8(H4) as the predominant menaquinone and C18 :
      1omega9c, iso-C16 : 0, C17 : 1omega8c and C16 : 0 as the major fatty acids. The
      genomic DNA G+C content of the novel strain was 71.1 mol%. The level of DNA-DNA
      relatedness between strain x-2T and N. panacisoli KCTC 19470T (=Gsoil 346T) was
      29.8 %. These chemotaxonomic characters support the position of strain x-2T
      within the genus Nocardioides. The results of physiological and biochemical
      tests, as well as phylogenetic analysis, suggest that strain x-2T represents a
      novel species of the genus Nocardioides, for which the name Nocardioides
      litorisoli sp. nov. is proposed. The type strain is x-2T (=KCTC 39845T=CCTCCAB
      2016255T).

PMID- 29022547
TI  - Oceanibaculum nanhaiense sp. nov., isolated from surface seawater.
AB  - A taxonomic study was carried out on strain L54-1-50T, which was isolated from
      surface seawater of the South China Sea. Cells of strain L54-1-50T were Gram
      stain-negative, rod-shaped, oxidase-positive and catalase-positive. Growth was
      observed at salinities from 0 to 9 % (optimum 2 %, w/v), at pH 6.0-10.0 (optimum
      8.0-9.0) and at temperatures from 10 to 45  degrees C (optimum 25-37  degrees C),
      but not at 4 or 50  degrees C. The 16S rRNA gene sequence analysis indicated that
      strain L54-1-50T was a member of the genus Oceanibaculum, related to
      Oceanibaculum indicum P24T (98.8 %) and Oceanibaculum pacificum MC2UP-L3T (97.7
      %). The digital DNA-DNA hybridization values between strain L54-1-50T and the two
      type strains O. indicum P24T and O. pacificum MC2UP-L3T were 35.4+/-2.5 and
      23.7+/-2.5 %, respectively. The average nucleotide identity values between strain
      L54-1-50T and two type strains were 79.7 and 88.3 %, respectively. The major
      cellular fatty acids were summed feature 8 (C18 : 1omega7c and/or C18 :
      1omega6c), C16 : 0 and C18 : 1 2-OH. The respiratory quinone was Q-10. The polar
      lipids comprised diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylmonomethylethanolamine, phosphatidylglycerol, two unidentified
      phospholipids and three unidentified lipids. The G+C content of the chromosomal
      DNA was 65.1 mol%. The combined genotypic and phenotypic data showed that strain
      L54-1-50T represents a novel species of the genus Oceanibaculum, for which the
      name Oceanibaculumnanhaiense sp. nov. is proposed, with the type strain L54-1-50T
      (=KCTC 52312T=MCCC 1A05150T).

PMID- 29022548
TI  - Frondibacter mangrovi sp. nov., a member of the family Flavobacteriaceae isolated
      from seawater by in situ cultivation, and emended description of Frondibacter
      aureus.
AB  - A Gram-stain-negative, rod-shaped, non-motile, strictly aerobic,
      chemoheterotrophic, light-yellow-pigmented bacterium, designated strain 02OK1/10
      76T, was isolated from a mangrove estuary in Japan by use of an in situ
      cultivation technique. Preliminary analysis based on the 16S rRNA gene sequence
      revealed that the novel isolate was affiliated with the family Flavobacteriaceae
      of the phylum Bacteroidetes and that it showed highest sequence similarity (96.9
      %) to Frondibacter aureus A5Q-67T. The DNA G+C content of strain 02OK1/10-76T was
      35 mol%; MK-6 was the only menaquinone; and iso-C15 : 0, iso-C17 : 0 3-OH and iso
      C16 : 0 3-OH were the major (>10 %) cellular fatty acids. The polar lipid profile
      consisted of phosphatidylethanolamine, three unidentified aminolipids, an
      unidentified aminophospholipid and an unidentified lipid. From the distinct
      phylogenetic position and combination of genotypic and phenotypic
      characteristics, the strain represents a novel species of the genus Frondibacter,
      for which the name Frondibacter mangrovi sp. nov. is proposed. The type strain is
      02OK1/10-76T (= KCTC 52666T = NBRC 112695T). An emended description of F. aureus
      is also provided.

PMID- 29022549
TI  - Altererythrobacter mangrovi sp. nov., isolated from mangrove sediment.
AB  - A Gram-stain-negative, facultative anaerobic, yellow-pigmented, rod-shaped, non
      flagellum and non-motile bacterial strain, designed C9-11T, was isolated from
      mangrove sediment in Zhangzhou, Fujian Province, China. Growth was observed at
      temperatures from 15 to 37  degrees C (optimum 30  degrees C), at salinities from
      0 to 4 % (optimum 0.5-2 %) and at pH from 6 to 8 (optimum 7). Phylogenetic
      analysis based on 16S rRNA gene sequence revealed that strain C9-11T was a member
      of the genus Altererythrobacter. Strain C9-11T was related most closely to
      Altererythrobacter oceanensis Y2T (96.8 % 16S rRNA gene sequence similarity),
      followed by Altererythrobacter marinus H32T (96.5 %). The G+C content of the
      genomic DNA was 63.5 mol%. The dominant fatty acids were C18 : 1omega7c (41.6 %),
      C17 : 1omega6c (15.4 %), 11-methyl C18 : 1omega7c (8.1 %), summed feature 3
      (comprising C16 : 1omega7c and/or C16 : 1omega6c 7.4 %) and C16 : 0 (6.2 %). The
      predominant respiratory quinone was ubiquinone-10 and the major polar lipids were
      diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine,
      phosphatidylglycerol and sphingoglycolipid. According to its morphology,
      physiology, fatty acid composition and 16S rRNA gene sequence analysis, strain C9
      11Tbelongs to genus Altererythrobacter, but can readily be distinguished from
      recognized species. Strain C9-11T is proposed as the type strain of a novel
      species of the genus Altererythrobacter, for which the
      nameAltererythrobactermangrovi sp. nov (=MCCC 1K03311T=JCM 32056T) is proposed.

PMID- 29022551
TI  - Lentzea pudingi sp. nov., isolated from a weathered limestone sample in a karst
      area.
AB  - A novel Gram-stain-positive, aerobic bacterium, designated strain DHS C021T, was
      isolated from a limestone sample collected from the Puding Karst Ecosystem
      Research Station of Guizhou Province, southwest China. This strain developed
      branched vegetative mycelia, and its aerial mycelia fragmented into rod-shaped
      spores. The cell-wall peptidoglycan contained meso-diaminopimelic acid and the
      whole-cell sugars comprised galactose, ribose and mannose. The respiratory
      quinone was identified as menaquinone MK-9(H4). The major cellular fatty acids
      were iso-C14 : 0 and iso-C16 : 0. The phospholipids detected were
      diphosphatidylglycerol, phosphatidylethanolamine, hydroxyl
      phosphatidyethanolamine, phosphatidylinositol, phosphotidylinositolmannosides and
      one unidentified phospholipid. The genomic DNA G+C content was 69.8 mol% and 16S
      rRNA gene sequence analysis showed that the strain belonged to the genus Lentzea
      and shared highest sequence similarity with Lentzeaalbida CGMCC 4.1727T (98.8 %)
      and Lentzea waywayandensis CGMCC 4.1646T (98.5 %). However, it could be
      distinguished from these reference strains based on the low levels of DNA-DNA
      relatedness (54.5+/-2.7 and 41.7+/-3.2 %, respectively). On the basis of
      morphological, chemotaxonomic and phylogenetic characteristics, and DNA-DNA
      hybridization data, strain DHS C021T represents a novel species of the genus
      Lentzea, for which the name Lentzeapudingi sp. nov. is proposed. The type strain
      is DHS C021T (=CGMCC 4.7319T=KCTC 39694T).

PMID- 29022550
TI  - Streptococcus gordonii pheromone s.g.cAM373 may influence the reservoir of
      antibiotic resistance determinants of Enterococcus faecalis origin in the oral
      metagenome.
AB  - Streptococcus gordonii produces a pheromone heptapeptide, s.g.cAM373, which
      induces a conjugative mating response in Enterococcus faecalis cells carrying the
      responsive plasmid, pAM373. We investigated the extent of this intergeneric
      signaling on DNA acquisition by streptococcal species likely to cohabit oral
      biofilms. E. faecalis/pAM373/pAMS470 cells were incubated with synthetic
      s.g.cAM373, reverse peptide s.g.cAM373-R, or peptide-free medium and examined for
      their abilities to transfer plasmid DNA to streptococcal species in the presence
      of DNase. Preinduction of E. faecalis donors with s.g.cAM373 resulted in
      transconjugation frequencies in non-pheromone producing strains of Streptococcus
      mutans, Streptococcus sanguinis, Streptococcus anginosus, and Streptococcus suis
      that were significantly higher than frequencies when donors were preincubated
      with s.g.cAM373-R or medium alone. Peptide-mediated communication between
      commensal streptococci and E. faecalis carrying pheromone-responsive plasmids may
      facilitate conjugative DNA transfer to bystander species, and influence the
      reservoir of antibiotic resistance determinants of enterococcal origin in the
      oral metagenome.

PMID- 29022552
TI  - Multiplex PCR for identification of six clinically relevant streptococci.
AB  - PURPOSE: The aim of this study was to develop a multiplex PCR (mPCR) for
      simultaneous detection (single reaction) of six clinically relevant streptococcal
      species: Streptococcus pneumoniae, Streptococcus suis, Streptococcus gallolyticus
      subsp. gallolyticus, S. gallolyticus subsp. pasteurianus, Streptococcus
      intermedius and Streptococcus anginosus/constellatus. METHODS: mPCR with primers
      specific for S. pneumoniae (lytA), S. suis (recN), S. gallolyticus subsp.
      gallolyticus (tanB), S. gallolyticus subsp. pasteurianus (SGPB0680 cell wall
      surface protein), S. intermedius (ily) and S. anginosus/constellatus (moaC) was
      employed with 37 reference bacterial strains and 442 clinical streptococcal
      isolates collected from seven tertiary hospitals in north-east Thailand. Results
      from this mPCR were compared to those obtained with the API 20 Strep and
      conventional biochemical tests. RESULTS: The six clinically relevant
      streptococcal species gave the expected amplification products of 229, 362, 531,
      723, 819 and 978 bp for S. pneumoniae, S. gallolyticus subsp. gallolyticus, S.
      gallolyticus subsp. pasteurianus, S. suis, S. intermedius and S. anginosus/S.
      constellatus, respectively. Non-specific reactions were not observed with the
      other bacterial species tested. For the 442 clinical streptococci, this mPCR
      assay confirmed the identity of the species in accordance with results obtained
      with the API 20 Strep and conventional biochemical tests. CONCLUSION: This mPCR
      can be applied to the rapid identification of pure cultures of these six
      streptococci. The test was shown to be rapid, simple and reliable for the
      identification of these streptococci at the species level. This assay should be
      useful for laboratory identification and surveillance of human infections by
      these bacterial species.

PMID- 29022554
TI  - Corrigendum: Description of two novel members of the family Erysipelotrichaceae:
      Ileibacterium valens gen. nov., sp. nov. and Dubosiella newyorkensis, gen. nov.,
      sp. nov., from the murine intestine, and emendation to the description of
      Faecalibacterium rodentium.

PMID- 29022553
TI  - Polynucleobacter aenigmaticus sp. nov. isolated from the permanently anoxic
      monimolimnion of a temperate meromictic lake.
AB  - The bacterial strain MWH-K35W1T was isolated from a permanently anoxic water
      layer of a meromictic lake located in the Austrian Salzkammergut area. The
      basically chemo-organoheterotrophic strain was isolated and maintained under
      aerobic conditions. Phylogenetic analyses of the 16S rRNA gene and the glutamine
      synthetase gene (glnA) of the strain suggested an affiliation to the genus
      Polynucleobacter and the cryptic species complex PnecC. Strain MWH-K35W1T shares
      with the type strains of the six free-living species of the genus
      Polynucleobacter affiliated with this species complex 16S rRNA gene sequence
      similarities of 99.6-99.9 %, while the type material of the obligate endosymbiont
      Polynucleobacternecessarius, which is also affiliated with this species complex,
      shares a gene sequence similarity of 99.1 %. Genome sequencing resulted in a
      genome size of 2.14 Mbp and a DNA G+C content of 45.98 mol%. Major fatty acids
      were C16 : 1omega7c, C18 : 1omega7c and C16 : 0. This strain is the first strain
      of the genus Polynucleobacter found to encode a proteorhodopsin-like protein but,
      in contrast to some other strains affiliated to this genus, it does not encode a
      putative anoxygenic photosynthesis system. Multilocus sequence analysis based on
      partial sequences of eight housekeeping genes, as well as average nucleotide
      identity (ANI) analyses, did not suggest that strain MWH-K35W1T belongs to a
      previously described species. We propose the name Polynucleobacter aenigmaticus
      for a novel species with strain MWH-K35W1T (=DSM 24006T=LMG 29706T) as the type
      strain.

PMID- 29022555
TI  - Cyberlindnera xishuangbannaensis f.a., sp. nov., a yeast isolated from rotting
      wood.
AB  - Three strains representing a novel species of yeast were isolated from samples of
      rotting wood collected from Xishuangbanna Tropical Rainforest in Yunnan Province,
      PR China. Phylogenetic analysis based on the concatenated sequences of the
      internal transcribed spacer (ITS) region and the D1/D2 domains of the large
      subunit (LSU) rRNA gene revealed that the novel species is a member of the genus
      Cyberlindnera, although the formation of ascospores was not observed. The novel
      species was related most closely to the type strain of the species Candida
      pattaniensis, but they had a 0.5 % sequence divergence (3 substitutions, 0 gap)
      in the D1/D2 domain and a 5.4 % sequence divergence (21 substitutions, 10 gaps)
      in the ITS region. The novel species could also be differentiated from the
      closely related species by some biochemical and physiological characteristics.
      The species name Cyberlindnera xishuangbannaensis f.a., sp. nov. is proposed to
      accommodate these strains, with NYNU 16752T (=CICC 33163T=CBS 14692T) designated
      as the type strain. The MycoBank number is MB 822199.

PMID- 29022556
TI  - Erratum: Mesonia maritimus sp. nov., isolated from seawater of the South Sea of
      Korea.

PMID- 29022557
TI  - Two Childhood Pheochromocytoma Cases due to von Hippel-Lindau Disease, One
      Associated with Pancreatic Neuroendocrine Tumor: A Very Rare Manifestation
AB  - von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited disorder,
      characterized by hemangioblastomas of the retina and central nervous system
      (CNS); renal cysts; clear cell carcinoma; pheochromocytoma (PCC); endolymphatic
      sac tumors; cystadenomas of the epididymis in males; broad ligament of uterus in
      females; pancreatic cysts; cystadenomas; and neuroendocrine tumors. We report two
      cases of VHL disease that presented with PCC as the first manifestation. Further
      clinical developments during follow-up, hemangioblastoma of CNS in one case and a
      pancreatic neuroendocrine tumor (PNET) in the second case led to the diagnosis of
      VHL disease. Genetic analyses of the two cases revealed p.Arg161Gln (c.482G>A)
      and p.Leu129Pro (c.386T>G) heterozygous missense mutations in the VHL gene,
      respectively. In children, PCC may be the only and/or initial manifestation of
      VHL with delayed manifestations of the syndrome in other organs. PNET is a very
      rare manifestation of VHL disease. To the best of our knowledge, this is only the
      second reported case presenting with a combination of a PNET and bilateral PCC as
      components of childhood VHL disease. Pediatric patients diagnosed with PCC should
      be investigated for genetic causes and especially for VHL.

PMID- 29022558
TI  - Klinefelter Syndrome in Childhood: Variability in Clinical and Molecular Findings
AB  - OBJECTIVE: Klinefelter syndrome (KS) is the most common (1/500-1/1000)
      chromosomal disorder in males, but only 10% of cases are identified in childhood.
      This study aimed to review the data of children with KS to assess the age and
      presenting symptoms for diagnosis, clinical and laboratory findings, together
      with the presence of comorbidities. METHODS: Twenty-three KS patients were
      analyzed retrospectively. Age at admission, presenting symptoms, comorbid
      problems, height, weight, pubertal status, biochemical findings, hormone
      profiles, bone mineral density and karyotype were evaluated. Molecular analysis
      was also conducted in patients with ambiguous genitalia. RESULTS: The median age
      of patients at presentation was 3.0 (0.04-16.3) years. Most of the cases were
      diagnosed prenatally (n=15, 65.2%). Other reasons for admission were scrotal
      hypospadias (n=3, 14.3%), undescended testis (n=2, 9.5%), short stature (n=1,
      4.8%), isolated micropenis (n=1, 4.8%) and a speech disorder (n=1, 4.8%). The
      most frequent clinical findings were neurocognitive disorders, speech impairment,
      social and behavioral problems and undescended testes. All except two patients
      were prepubertal at admission. Most of the patients (n=20, 86.9%) showed the
      classic 47,XXY karyotype. Steroid 5 alpha-reductase 2 gene and androgen receptor
      gene mutations were detected in two of the three cases with genital ambiguity.
      CONCLUSION: Given the large number of underdiagnosed KS patients before
      adolescence, pediatricians need to be aware of the phenotypic variability of KS
      in childhood. Genetic analysis in KS patients may reveal mutations associated
      with other forms of disorders of sex development besides KS.

PMID- 29022559
TI  - Tuberculosis, human immunodeficiency virus, and the immune reconstitution
      inflammatory syndrome.

PMID- 29022560
TI  - Topical therapy of psoriasis: Where do we stand?

PMID- 29022561
TI  - Upwardly mobile: Lowered hearing?

PMID- 29022563
TI  - Statistical medicine: An emerging medical specialty.
AB  - A large number of statistical tools are now used for medical decision in the core
      activities of diagnosis, treatment and prognosis. These tools provide undeniable
      help in improving medical outcomes. Prominent among them are uncertainty
      measurement by probability, medical indicators and indexes, reference ranges, and
      scoring systems. In addition are tools such as odds ratio, sensitivity,
      specificity and predictivities, area under the ROC curve, likelihood ratios, and
      cost-benefit analysis that are commonly applied in medical research but have
      implications for day-to-day clinical activities. These tools have so completely
      integrated into medical practice that statistical medicine by itself can stand
      alone as a medical specialty. Time has arrived to recognize statistical medicine
      as a medical specialty.

PMID- 29022564
TI  - Precursor B-cell acute lymphoblastic leukemia: An unusual cause of bilateral
      nephromegaly in an infant.

PMID- 29022565
TI  - Malignant orbital teratoma in a neonate: A clinicopathological case report.

PMID- 29022562
TI  - Ketogenic diet in endocrine disorders: Current perspectives.
AB  - Ketogenic diet (KD) is a high-fat, adequate-protein, and low-carbohydrate diet
      that leads to nutritional ketosis, long known for antiepileptic effects and has
      been used therapeutically to treat refractory epilepsy. This review attempts to
      summarize the evidence and clinical application of KD in diabetes, obesity, and
      other endocrine disorders. KD is usually animal protein based. An empiric
      vegetarian Indian variant of KD has been provided keeping in mind the Indian food
      habits. KD has beneficial effects on cardiac ischemic preconditioning, improves
      oxygenation in patients with respiratory failure, improves glycemic control in
      diabetics, is associated with significant weight loss, and has a beneficial
      impact on polycystic ovarian syndrome. Multivitamin supplementations are
      recommended with KD. Recently, ketones are being proposed as super-metabolic
      fuel; and KD is currently regarded as apt dietary therapy for "diabesity."

PMID- 29022566
TI  - Adenosine monophosphate- activated protein kinase- based classification of
      diabetes pharmacotherapy.

PMID- 29022567
TI  - Reply to letter to editor regarding the article, "Adenosine monophosphate
      activated protein kinase-based classification of diabetes pharmacotherapy".

PMID- 29022568
TI  - Erratum: Directly converting CO2 into a gasoline fuel.
AB  - This corrects the article DOI: 10.1038/ncomms15174.

PMID- 29022570
TI  - Arterial stiffness as a risk factor for clinical hypertension.
AB  - In patients with uncomplicated essential hypertension, cardiac output remains
      within normal ranges and intravascular volume is normal or low, assuming the
      presence of a sufficient Windkessel effect and usual resistance and compliance
      calculations. However, mean circulatory pressure is elevated in these patients.
      In addition, vascular resistance is augmented, and most importantly, the
      viscoelasticity of the cardiovascular system is substantially impaired. Such
      considerations are essential to understanding the mechanisms behind carotid
      femoral arterial stiffness, a major risk factor in individuals with hypertension.
      Arterial stiffness, measured from pulse wave velocity, is substantially increased
      in hypertension even independently of blood pressure levels. Structural vascular
      changes and endothelial dysfunction are consistently associated with vessel
      impairments in animal models of hypertension. Increased arterial stiffness has a
      major effect on pulse pressure (the difference between systolic and diastolic
      blood pressure), wave reflections, kidney function, and above all, cardiovascular
      risk. This increased cardiovascular risk is particularly deleterious in patients
      with hypertension and/or type 2 diabetes mellitus, who are at risk of both renal
      and cardiovascular events. In this Review, we discuss the importance of arterial
      stiffness in the diagnosis and management of hypertension and the need for new
      approaches for the treatment of hypertension in patients with or without diabetes
      and/or renal impairment.

PMID- 29022572
TI  - Pharmacotherapy: Aspirin discontinuation increases risk of cardiovascular events.

PMID- 29022573
TI  - Syphilis.

PMID- 29022569
TI  - Syphilis.
AB  - Treponema pallidum subspecies pallidum (T. pallidum) causes syphilis via sexual
      exposure or via vertical transmission during pregnancy. T. pallidum is renowned
      for its invasiveness and immune-evasiveness; its clinical manifestations result
      from local inflammatory responses to replicating spirochaetes and often imitate
      those of other diseases. The spirochaete has a long latent period during which
      individuals have no signs or symptoms but can remain infectious. Despite the
      availability of simple diagnostic tests and the effectiveness of treatment with a
      single dose of long-acting penicillin, syphilis is re-emerging as a global public
      health problem, particularly among men who have sex with men (MSM) in high-income
      and middle-income countries. Syphilis also causes several hundred thousand
      stillbirths and neonatal deaths every year in developing nations. Although
      several low-income countries have achieved WHO targets for the elimination of
      congenital syphilis, an alarming increase in the prevalence of syphilis in HIV
      infected MSM serves as a strong reminder of the tenacity of T. pallidum as a
      pathogen. Strong advocacy and community involvement are needed to ensure that
      syphilis is given a high priority on the global health agenda. More investment is
      needed in research on the interaction between HIV and syphilis in MSM as well as
      into improved diagnostics, a better test of cure, intensified public health
      measures and, ultimately, a vaccine.

PMID- 29022571
TI  - Epidemiology of cardiovascular disease in young individuals.
AB  - In the past 2 decades, a high prevalence of risk factors for cardiovascular
      disease, such as obesity, physical inactivity, and poor diet, has been observed
      among young individuals living in developed countries. The rate of substance
      abuse (opioids, cocaine, electronic cigarettes, and anabolic steroids) is also
      increasing among young adults, whereas cigarette smoking might be declining.
      Among younger individuals (aged 18-50 years), the incidence of cardiovascular
      diseases over the same time period has either been steady or has increased, in
      contrast to the trend towards a lower incidence of cardiovascular disease in
      adults aged >50 years. Current observations might, therefore, be used to forecast
      a potential epidemic of cardiovascular disease in the near future as the younger
      segment of the population ages. In this Review, we discuss the burden of risk
      factors for ischaemic heart disease, heart failure, atrial fibrillation, and
      sudden cardiac death among young adults aged 18-45 years. Furthermore, we discuss
      the prevalence, incidence, and temporal trends of various cardiovascular diseases
      among this young segment of the population.

PMID- 29022574
TI  - Osthole prevents acetaminophen-induced liver injury in mice.
AB  - Acetaminophen (APAP) overdose leads to severe hepatotoxicity. Osthole, a natural
      coumarin found in traditional Chinese medicinal herbs, has therapeutic potential
      in the treatment of various diseases. In this study, we investigated the effects
      of osthole against APAP-induced hepatotoxicity in mice. Mice were administered
      osthole (100 mg.kg-1.d-1, ip) for 3 d, then on the fourth day APAP (300 mg/kg,
      ip) was co-administered with osthole. The mice were euthanized post-APAP, their
      serum and livers were collected for analysis. Pretreatment with osthole
      significantly attenuated APAP-induced hepatocyte necrosis and the increases in
      ALT and AST activities. Compared with the mice treated with APAP alone, osthole
      pretreatment significantly reduced serum MDA levels and hepatic H2O2 levels, and
      improved liver GSH levels and the GSSG-to-GSH ratio. Meanwhile, osthole
      pretreatment markedly alleviated the APAP-induced up-regulation of inflammatory
      cytokines in the livers, and inhibited the expression of hepatic cytochrome P450
      enzymes, but it increased the expression of hepatic UDP-glucuronosyltransferases
      (UGTs) and sulfotransferases (SULTs). Furthermore, osthole pretreatment reversed
      APAP-induced reduction of hepatic cAMP levels, but pretreatment with H89, a
      potent selective PKA inhibitor, failed to abolish the beneficial effect of
      osthole, whereas pretreatment with L-buthionine sulfoximine, a GSH synthesis
      inhibitor, abrogated the protective effects of osthole on APAP-induced liver
      injury, and abolished osthole-caused alterations in APAP-metabolizing enzymes. In
      cultured murine primary hepatocytes and Raw264.7 cells, however, osthole (40
      MUmol/L) did not alleviate APAP-induced cell death, but it significantly
      suppressed APAP-caused elevation of inflammatory cytokines. Collectively, we have
      demonstrated that osthole exerts a preventive effect against APAP-induced
      hepatotoxicity by inhibiting the metabolic activation of APAP and enhancing its
      clearance through an antioxidation mechanism.

PMID- 29022575
TI  - Gefitinib inhibits M2-like polarization of tumor-associated macrophages in Lewis
      lung cancer by targeting the STAT6 signaling pathway.
AB  - M2-like polarized tumor-associated macrophages (TAMs) play a pivotal role in
      promoting cancer cell growth, invasion, metastasis and angiogenesis. The
      identification of M2-like TAMs during tumor progression is an attractive approach
      for cancer therapy. In this study, we investigated the relevance of macrophage
      polarization and the antitumor effect of gefitinib in Lewis Lung cancer (LLC) in
      vitro and in vivo. Gefitinib at a concentration below 2.5 MUmol/L did not cause
      significant growth inhibition on LLC and RAW 264.7 cell lines and bone marrow
      derived macrophage (BMDMs). However, a small concentration of gefitinib (0.62
      MUmol/L) significantly inhibited IL-13-induced M2-like polarization of
      macrophages, evidenced by the decreased expression of the M2 surface markers
      CD206 and CD163, down-regulation of specific M2-marker genes (Mrc1, Ym1, Fizz1,
      Arg1, IL-10 and CCL2) as well as inhibition of M2-like macrophage-mediated
      invasion and migration of LLC cells. In RAW 264.7 cells, gefitinib inhibits IL-13
      induced phosphorylation of STAT6, which was a crucial signaling pathway in
      macrophage M2-like polarization. In LLC mice metastasis model, oral
      administration of gefitinib (75 mg.kg-1.d-1, for 21 d) significantly reduced the
      number of lung metastasis nodules, down-regulated the expression of M2 marker
      genes and the percentages CD206+ and CD68+ macrophages in tumor tissues. These
      results demonstrated that gefitinib effectively inhibits M2-like polarization
      both in vitro and in vivo, revealing a novel potential mechanism for the
      chemopreventative effect of gefitinib.

PMID- 29022577
TI  - Human genomics: Cracking the regulatory code.

PMID- 29022578
TI  - Engineering: Liquid metal pumped at a record temperature.

PMID- 29022576
TI  - Xueshuantong injection (lyophilized) combined with salvianolate lyophilized
      injection protects against focal cerebral ischemia/reperfusion injury in rats
      through attenuation of oxidative stress.
AB  - Salvianolate lyophilized injection (SLI) and Xueshuantong injection (lyophilized)
      (XST) are two herbal standardized preparations that have been widely used in
      China for the treatment of acute cerebral infarction. In this study, we
      investigated the neuroprotective effects of SLI combined with XST in a rat model
      of middle cerebral artery occlusion-reperfusion (MCAO/R). Wistar rats were
      subjected to 1.5 h of MCAO followed by reperfusion for 3 h, then were treated
      with SLI or XST alone, or with their combinations via tail vein injection daily
      for 3 d. Edaravone (EDI, 6 mg.kg-1.d-1) was used as a positive control drug, We
      showed that administration of a combination of 1X1S (XST 100 mg.kg-1.d-1 plus SLI
      21 mg.kg-1.d-1) more effectively protected the ischemic brains than SLI or XST
      used alone. Administration of 1X1S not only significantly decreased neurological
      deficit scores and infarct volumes and increased regional cerebral blood flow,
      but also inhibited the activation of both microglia and astrocytes in the
      hippocampus. Furthermore, administration of 1X1S significantly decreased the
      levels of MDA and ROS with concomitant increases in the levels of antioxidant
      activity (SOD, CAT and GSH) in the brain tissues as compared with SLI and XST
      used alone. Moreover, administration of 1X1S remarkably upregulated the
      expression of Nrf-2, HO-1 and NQO-1, and downregulated the expression of Keap1
      and facilitated the nuclear translocation of Nrf-2 in the brain tissues as
      compared with XST used alone. Our study demonstrates that a combination of 1X1S
      effectively protects MCAO/R injury via suppressing oxidative stress and the Nrf
      2/Keap1 pathway.

PMID- 29022579
TI  - Natural hazards: Risk assessments face legal scrutiny.

PMID- 29022580
TI  - Correction.

PMID- 29022584
TI  - Brain modelling: Does the brain control foraging?

PMID- 29022585
TI  - Cancer care: Tap latent source of frugal cancer ideas.

PMID- 29022588
TI  - Predatory journals: Research that isn't read doesn't exist.

PMID- 29022590
TI  - Pumping liquid metal at high temperatures up to 1,673 kelvin.
AB  - Heat is fundamental to power generation and many industrial processes, and is
      most useful at high temperatures because it can be converted more efficiently to
      other types of energy. However, efficient transportation, storage and conversion
      of heat at extreme temperatures (more than about 1,300 kelvin) is impractical for
      many applications. Liquid metals can be very effective media for transferring
      heat at high temperatures, but liquid-metal pumping has been limited by the
      corrosion of metal infrastructures. Here we demonstrate a ceramic, mechanical
      pump that can be used to continuously circulate liquid tin at temperatures of
      around 1,473-1,673 kelvin. Our approach to liquid-metal pumping is enabled by the
      use of ceramics for the mechanical and sealing components, but owing to the
      brittle nature of ceramics their use requires careful engineering. Our set-up
      enables effective heat transfer using a liquid at previously unattainable
      temperatures, and could be used for thermal storage and transport, electric power
      production, and chemical or materials processing.

PMID- 29022594
TI  - Countries: Avoid glib terms of development status.

PMID- 29022581
TI  - The impact of rare variation on gene expression across tissues.
AB  - Rare genetic variants are abundant in humans and are expected to contribute to
      individual disease risk. While genetic association studies have successfully
      identified common genetic variants associated with susceptibility, these studies
      are not practical for identifying rare variants. Efforts to distinguish
      pathogenic variants from benign rare variants have leveraged the genetic code to
      identify deleterious protein-coding alleles, but no analogous code exists for non
      coding variants. Therefore, ascertaining which rare variants have phenotypic
      effects remains a major challenge. Rare non-coding variants have been associated
      with extreme gene expression in studies using single tissues, but their effects
      across tissues are unknown. Here we identify gene expression outliers, or
      individuals showing extreme expression levels for a particular gene, across 44
      human tissues by using combined analyses of whole genomes and multi-tissue RNA
      sequencing data from the Genotype-Tissue Expression (GTEx) project v6p release.
      We find that 58% of underexpression and 28% of overexpression outliers have
      nearby conserved rare variants compared to 8% of non-outliers. Additionally, we
      developed RIVER (RNA-informed variant effect on regulation), a Bayesian
      statistical model that incorporates expression data to predict a regulatory
      effect for rare variants with higher accuracy than models using genomic
      annotations alone. Overall, we demonstrate that rare variants contribute to large
      gene expression changes across tissues and provide an integrative method for
      interpretation of rare variants in individual genomes.

PMID- 29022595
TI  - Astronomy: Ring detected around a dwarf planet.

PMID- 29022593
TI  - The size, shape, density and ring of the dwarf planet Haumea from a stellar
      occultation.
AB  - Haumea-one of the four known trans-Neptunian dwarf planets-is a very elongated
      and rapidly rotating body. In contrast to other dwarf planets, its size, shape,
      albedo and density are not well constrained. The Centaur Chariklo was the first
      body other than a giant planet known to have a ring system, and the Centaur
      Chiron was later found to possess something similar to Chariklo's rings. Here we
      report observations from multiple Earth-based observatories of Haumea passing in
      front of a distant star (a multi-chord stellar occultation). Secondary events
      observed around the main body of Haumea are consistent with the presence of a
      ring with an opacity of 0.5, width of 70 kilometres and radius of about 2,287
      kilometres. The ring is coplanar with both Haumea's equator and the orbit of its
      satellite Hi'iaka. The radius of the ring places it close to the 3:1 mean-motion
      resonance with Haumea's spin period-that is, Haumea rotates three times on its
      axis in the time that a ring particle completes one revolution. The occultation
      by the main body provides an instantaneous elliptical projected shape with axes
      of about 1,704 kilometres and 1,138 kilometres. Combined with rotational light
      curves, the occultation constrains the three-dimensional orientation of Haumea
      and its triaxial shape, which is inconsistent with a homogeneous body in
      hydrostatic equilibrium. Haumea's largest axis is at least 2,322 kilometres,
      larger than previously thought, implying an upper limit for its density of 1,885
      kilograms per cubic metre and a geometric albedo of 0.51, both smaller than
      previous estimates. In addition, this estimate of the density of Haumea is closer
      to that of Pluto than are previous estimates, in line with expectations. No
      global nitrogen- or methane-dominated atmosphere was detected.

PMID- 29022596
TI  - An ace in the hole for DNA sequencing.

PMID- 29022589
TI  - Dynamic landscape and regulation of RNA editing in mammals.
AB  - Adenosine-to-inosine (A-to-I) RNA editing is a conserved post-transcriptional
      mechanism mediated by ADAR enzymes that diversifies the transcriptome by altering
      selected nucleotides in RNA molecules. Although many editing sites have recently
      been discovered, the extent to which most sites are edited and how the editing is
      regulated in different biological contexts are not fully understood. Here we
      report dynamic spatiotemporal patterns and new regulators of RNA editing,
      discovered through an extensive profiling of A-to-I RNA editing in 8,551 human
      samples (representing 53 body sites from 552 individuals) from the Genotype
      Tissue Expression (GTEx) project and in hundreds of other primate and mouse
      samples. We show that editing levels in non-repetitive coding regions vary more
      between tissues than editing levels in repetitive regions. Globally, ADAR1 is the
      primary editor of repetitive sites and ADAR2 is the primary editor of non
      repetitive coding sites, whereas the catalytically inactive ADAR3 predominantly
      acts as an inhibitor of editing. Cross-species analysis of RNA editing in several
      tissues revealed that species, rather than tissue type, is the primary
      determinant of editing levels, suggesting stronger cis-directed regulation of RNA
      editing for most sites, although the small set of conserved coding sites is under
      stronger trans-regulation. In addition, we curated an extensive set of ADAR1 and
      ADAR2 targets and showed that many editing sites display distinct tissue-specific
      regulation by the ADAR enzymes in vivo. Further analysis of the GTEx data
      revealed several potential regulators of editing, such as AIMP2, which reduces
      editing in muscles by enhancing the degradation of the ADAR proteins.
      Collectively, our work provides insights into the complex cis- and trans
      regulation of A-to-I editing.

PMID- 29022599
TI  - Findings of Research Misconduct.

PMID- 29022600
TI  - A porous Ru nanomaterial as an efficient electrocatalyst for the hydrogen
      evolution reaction under acidic and neutral conditions.
AB  - A porous Ru nanomaterial exhibits high electrocatalytic performance and excellent
      durability for the hydrogen evolution reaction (HER) under both acidic and
      neutral conditions. It displays a low overpotential of 83 mV at a current density
      of 10 mA cm-2 and an excellent durability up to 12 h in 0.5 M H2SO4.

PMID- 29022601
TI  - Boron-nitrogen main chain analogues of polystyrene: poly(B-aryl)aminoboranes via
      catalytic dehydrocoupling.
AB  - The first high molar mass polyaminoboranes with an organic substituent at boron,
      namely the B-arylated polyaminoboranes [NH2-BHPh]n (2a) and [NH2-BH(p-CF3C6H4)]n
      (2b), have been prepared via catalytic dehydropolymerisation. These materials can
      be considered as inorganic analogues of polystyrene with a B-N main chain. Their
      synthesis was achieved from B-aryl amine-borane precursors in solution using an
      [IrH2(POCOP)] precatalyst.

PMID- 29022602
TI  - A novel CuZnInS quantum dot-based ECL sensing system for lysophosphatidic acid
      detection.
AB  - In this paper, a novel electrochemiluminescence (ECL) sensor for lysophosphatidic
      acid (LPA) detection was developed. LPA consists of a phosphate "head" group, a
      "linker" region illustrated by glycerol, and a fatty acyl chain as a lipophilic
      "tail". The water-soluble quaternary CuInZnS quantum dots (QDs) were modified
      with agmatine (AGM) molecules as an ECL luminophore. On the one hand, the
      guanidine groups on the QDs can capture the hydrophilic head of LPA with high
      selectivity. On the other hand, the electrochemically reduced graphene nanosheets
      (GNs) modified on the glassy carbon electrode (GCE) surface can bind the LPA
      lipophilic tail. As a result, the LPA-AGM-CuInZnS QDs were captured on the
      GNs/GCE. The ECL intensity of the system was enhanced with the increased
      concentration of LPA. As far as we know, it was the first report about LPA
      detection based on the ECL nanosensing system. The linear relationship range of
      LPA sensing is from 2 to 75 MUmol L-1. The practicability of this ECL sensing
      platform had shown satisfactory results in human serum samples.

PMID- 29022604
TI  - Assembly of high-symmetry silver(i) alkyl-1,3-diynyl cluster complexes via core
      transformation.
AB  - New tetranuclear supramolecular precursors [(R-C[triple bond, length as m-dash]C
      C[triple bond, length as m-dash]C)Ag(PPh3)]4 (R = iPr and chx) are employed to
      construct three polynuclear silver(i) alkyl-1,3-diynyl cluster complexes (1-3)
      that bear the same novel trigonal bipyramidal Ag5 core consolidated by silver
      ethynide and argentophilic interactions. The present results strongly suggest
      that the assembly of high-symmetry medium-nuclearity clusters 1-3 is initiated by
      the accretion of additional Ag(i) ions by the Ag4 template of the precursors
      through argentophilic (<3.4 A) interaction, and demonstrate that core
      transformation is an effective synthetic route to high-symmetry metal clusters.

PMID- 29022603
TI  - Poly(N-isopropylacrylamide) modified polydopamine as a temperature-responsive
      surface for cultivation and harvest of mesenchymal stem cells.
AB  - A thermo-responsive surface was fabricated by depositing poly(N
      isopropylacrylamide) (PNIPAAm) onto polydopamine coated cell culture substrata
      through free radical polymerization for the purpose of culturing and harvesting
      human mesenchymal stem cells (hMSCs). Human MSCs were cultured onto the PNIPAAm-g
      polydopamine coated surface and harvested by changing from physiological to
      ambient temperature. The produced PNIPAAm-g-polydopamine surface was
      characterized by atomic force microscopy, Fourier transform infrared
      spectroscopy, nuclear magnetic resonance, water contact angle measurement,
      differential scanning calorimetry, and cell culture studies. Our results revealed
      that hMSCs could be detached from the PNIPAAm-g-polydopamine surface within 60
      min after switching the temperature from 37  degrees C to room temperature. The
      detached hMSCs were able to proliferate on the PNIPAAm-g-polydopamine coated
      surface for further growth and harvest.

PMID- 29022605
TI  - The promotion effects of thionation and isomerization on charge carrier mobility
      in naphthalene diimide crystals.
AB  - Herein, the promotion effects of thionation and isomerization on the carrier
      mobility properties of naphthalene diimide and thionated naphthalene diimide
      crystals were investigated in detail based on the Marcus-Hush theory and quantum
      chemical calculations. The thionation of NDIs will improve the charge mobility of
      both electrons and holes, which is similar to the thionation of PDIs. The
      compound P only behaves as an n-type organic semiconductor (OSC), whereas the
      three other thionation structures have higher mobility values and can behave as p
      type OSCs. For the cis/trans isomers of the two double-thionation structures,
      trans-S2 has a larger hole and electron carrier mobility than cis-S2; this is
      consistent with the experimental results obtained for cis-trans-isomers. A
      potential strategy for the development of high performance ambipolar OSCs is the
      substitution of O atoms by S atoms. These results will provide a guide for the
      design and optimization of OSCs via analysis of the relationship between carrier
      mobility and molecular crystal structures.

PMID- 29022609
TI  - High-resolution microstrip NMR detectors for subnanoliter samples.
AB  - We present the numerical optimization and experimental characterization of two
      microstrip-based nuclear magnetic resonance (NMR) detectors. The first detector,
      introduced in our previous work, was a flat wire detector with a strip resting on
      a substrate, and the second detector was created by adding a ground plane on top
      of the strip conductor, separated by a sample-carrying capillary and a thin layer
      of insulator. The dimensional parameters of the detectors were optimized using
      numerical simulations with regards to radio frequency (RF) sensitivity and
      homogeneity, with particular attention given to the effect of the ground plane.
      The influence of copper surface finish and substrate surface on the spectral
      resolution was investigated, and a resolution of 0.8-1.5 Hz was obtained on 1 nL
      deionized water depending on sample positioning. For 0.13 nmol sucrose (0.2 M in
      0.63 nL H2O) encapsulated between two Fluorinert plugs, high RF homogeneity (A810
      degrees /A90 degrees  = 70-80%) and high sensitivity (expressed in the limit of
      detection nLODm = 0.73-1.21 nmol s1/2) were achieved, allowing for high
      performance 2D NMR spectroscopy of subnanoliter samples.

PMID- 29022608
TI  - The development of novel Au/CaO nanoribbons from bifunctional building block for
      biodiesel production.
AB  - Herein, a novel and facile high-yield strategy is reported to efficiently
      fabricate 1D self-supported Au/CaO nanocatalysts using dual metal co-ordination
      polymers as templates. Significantly, a uniform distribution of dual metal
      nanoparticles can be ensured due to the fact that both Ca2+ and Au3+ ions are
      initially introduced into the co-ordination polymer via chemical bonding with
      bifunctional organic linkers and then, the Au and CaO nanoparticles are formed
      simultaneously in one pot via calcination. Furthermore, the as-prepared Au/CaO
      nanoribbons exhibit excellent catalytic performance in the transesterification
      reaction, which can be attributed to the small size and high distribution of CaO
      nanoparticles as well as the special 1D structure with high surface area.
      Moreover, leaching and deactivation, which are the main problems of CaO-based
      catalysts, are remarkably reduced due to the presence of hydrophobic Au
      nanoparticles on the surface of the CaO nanoribbons. Consequently, the Au/CaO
      nanoribbons can be used as recyclable catalysts with high activity for biodiesel
      production.

PMID- 29022606
TI  - Zinc supplementation mitigates its dyshomeostasis in experimental diabetic rats
      by regulating the expression of zinc transporters and metallothionein.
AB  - Zinc depletion during diabetes projects a role for zinc nutrition in this
      condition. This study explored whether zinc supplementation annuls diabetes
      induced zinc dyshomeostasis through modulation of zinc transporters and
      metallothionein. Groups of hyperglycemic rats were exposed for six weeks to
      supplemental zinc (5 or 10-times the normal level). Intracellular zinc
      concentration and zinc transporter and metallothionein expression levels in
      different tissues were analysed. Depleted zinc concentrations in different organs
      were restored by zinc supplementation. Zinc ions cross biological membranes with
      the aid of membrane proteins, belonging to zinc transporter families - ZIPs
      (responsible for the influx) and ZnTs (responsible for intracellular
      traffic/efflux). Up-regulated expression levels of zinc efflux proteins and
      influx proteins were beneficially modulated by zinc treatment, which also induced
      metallothionein expression in tissues to mitigate oxidative stress. Thus, zinc
      supplementation has a significant benefit in controlling zinc fluxes during
      diabetes, exerted through a protective influence on the modulation of the
      expression of zinc transporters and metallothionein.

PMID- 29022614
TI  - Photochemical upconversion in water.
AB  - A major challenge remaining in photochemical upconversion lies in identifying
      appropriate chromophore combinations that function in pure water in the absence
      of hydrophobic hosts or surfactant additives. The current investigation achieves
      this goal using combinations of water soluble Ru(ii) metal-to-ligand charge
      transfer (MLCT) sensitizers in concert with 9-anthracenecarboxylate (AnCO2-) and
      1-pyrenecarboxylate (PyCO2-) in neat H2O.

PMID- 29022615
TI  - Principles of mucin structure: implications for the rational design of cancer
      vaccines derived from MUC1-glycopeptides.
AB  - Cancer is currently one of the world's most serious public health problems.
      Significant efforts are being made to develop new strategies that can eradicate
      tumours selectively without detrimental effects to healthy cells. One promising
      approach is focused on the design of vaccines that contain partially glycosylated
      mucins in their formulation. Although some of these vaccines are in clinical
      trials, a lack of knowledge about the molecular basis that governs the antigen
      presentation, and the interactions between antigens and the elicited antibodies
      has limited their success thus far. This review focuses on the most significant
      milestones achieved to date in the conformational analysis of tumour-associated
      MUC1 derivatives both in solution and bound to antibodies. The effect that the
      carbohydrate scaffold has on the peptide backbone structure and the role of the
      sugar in molecular recognition by antibodies are emphasised. The outcomes
      summarised in this review may be a useful guide to develop new antigens for the
      design of cancer vaccines in the near future.

PMID- 29022617
TI  - Two titanium(iv)-oxo-clusters: synthesis, structures, characterization and
      recycling catalytic activity in the oxygenation of sulfides.
AB  - Two 5-sulfosalicylic acid (H3ssal) and 1,10-phenanthroline (Phen) substituted
      titanium-oxo-clusters, [Ti6O8 (Hssal)2(Phen)6(H2O)4].4OH.21H2O (TOC-1) and
      [Ti4O4(Hssal)4(Phen)4].18H2O.4NH3 (TOC-2), have been synthesized and fully
      characterized by single crystal X-ray diffraction, FT-IR spectroscopy, elemental
      analysis, thermogravimetric analysis and fluorescence analysis. The structure of
      TOC-1 is a hexanuclear cluster containing a {Ti6(MU2-O)8} core, where all
      titanium ions can be described in a distorted octahedral geometry with both 1,10
      phenanthroline and 5-sulfosalicylate serving as chelating ligands, while TOC-2
      consists of a tetranuclear {Ti4(MU2-O)4} skeleton forming an approximate plane
      quadrilateral where both 5-sulfosalicylate and 1,10-phenanthroline ligands
      chelate to the titanium atom and the oxygen atom bridges two titanium atoms.
      Moreover, catalytic activity for the selective oxidation of sulfides, methyl
      phenyl sulfide (MPS) and phenyl sulfide (PPS), has also been explored. The
      results showed that TOCs 1 and 2 exhibit excellent catalytic performance in the
      oxidation of sulfides to sulfoxides with H2O2 as an oxidant. In particular, TOC-1
      is an efficient homogeneous catalyst and very interestingly it can be recovered
      by filtration upon cooling and then reused at least four times without losing
      activity, which is very rare in the oxygenation of organic sulfides.

PMID- 29022618
TI  - Enhancing the resolution of 1H and 13C solid-state NMR spectra by reduction of
      anisotropic bulk magnetic susceptibility broadening.
AB  - We demonstrate that natural isotopic abundance 2D heteronuclear correlation
      (HETCOR) solid-state NMR spectra can be used to significantly reduce or eliminate
      the broadening of 1H and 13C solid-state NMR spectra of organic solids due to
      anisotropic bulk magnetic susceptibility (ABMS). ABMS often manifests in solids
      with aromatic groups, such as active pharmaceutical ingredients (APIs), and
      inhomogeneously broadens the NMR peaks of all nuclei in the sample. Inhomogeneous
      peaks with full widths at half maximum (FWHM) of ~1 ppm typically result from
      ABMS broadening and the low spectral resolution impedes the analysis of solid
      state NMR spectra. ABMS broadening of solid-state NMR spectra has previously been
      eliminated using 2D multiple-quantum correlation experiments, or by performing
      NMR experiments on diluted materials or single crystals. However, these
      experiments are often infeasible due to their poor sensitivity and/or provide
      limited gains in resolution. 2D 1H-13C HETCOR experiments have previously been
      applied to reduce susceptibility broadening in paramagnetic solids and we show
      that this strategy can significantly reduce ABMS broadening in diamagnetic
      organic solids. Comparisons of 1D solid-state NMR spectra and 1H and 13C solid
      state NMR spectra obtained from 2D 1H-13C HETCOR NMR spectra show that the HETCOR
      spectrum directly increases resolution by a factor of 1.5 to 8. The direct gain
      in resolution is determined by the ratio of the inhomogeneous 13C/1H linewidth to
      the homogeneous 1H linewidth, with the former depending on the magnitude of the
      ABMS broadening and the strength of the applied field and the latter on the
      efficiency of homonuclear decoupling. The direct gains in resolution obtained
      using the 2D HETCOR experiments are better than that obtained by dilution. For
      solids with long proton longitudinal relaxation times, dynamic nuclear
      polarization (DNP) was applied to enhance sensitivity and enable the acquisition
      of 2D 1H-13C HETCOR NMR spectra. 2D 1H-13C HETCOR experiments were applied to
      resolve and partially assign the NMR signals of the form I and form II polymorphs
      of aspirin in a sample containing both forms. These findings have important
      implications for ultra-high field NMR experiments, optimization of decoupling
      schemes and assessment of the fundamental limits on the resolution of solid-state
      NMR spectra.

PMID- 29022598
TI  - Landscape of X chromosome inactivation across human tissues.
AB  - X chromosome inactivation (XCI) silences transcription from one of the two X
      chromosomes in female mammalian cells to balance expression dosage between XX
      females and XY males. XCI is, however, incomplete in humans: up to one-third of X
      chromosomal genes are expressed from both the active and inactive X chromosomes
      (Xa and Xi, respectively) in female cells, with the degree of 'escape' from
      inactivation varying between genes and individuals. The extent to which XCI is
      shared between cells and tissues remains poorly characterized, as does the degree
      to which incomplete XCI manifests as detectable sex differences in gene
      expression and phenotypic traits. Here we describe a systematic survey of XCI,
      integrating over 5,500 transcriptomes from 449 individuals spanning 29 tissues
      from GTEx (v6p release) and 940 single-cell transcriptomes, combined with genomic
      sequence data. We show that XCI at 683 X-chromosomal genes is generally uniform
      across human tissues, but identify examples of heterogeneity between tissues,
      individuals and cells. We show that incomplete XCI affects at least 23% of X
      chromosomal genes, identify seven genes that escape XCI with support from
      multiple lines of evidence and demonstrate that escape from XCI results in sex
      biases in gene expression, establishing incomplete XCI as a mechanism that is
      likely to introduce phenotypic diversity. Overall, this updated catalogue of XCI
      across human tissues helps to increase our understanding of the extent and impact
      of the incompleteness in the maintenance of XCI.

PMID- 29022619
TI  - Visible-light-mediated radical cascade reaction: synthesis of 3-bromocoumarins
      from alkynoates.
AB  - A visible-light-mediated radical addition of alkynoates to generate 3
      bromocoumarins by using N-bromosuccinimide as the bromo source has been
      accomplished. This procedure provides a bromo radical
      addition/spirocyclization/ester migration cascade reaction under very mild
      reaction conditions without using any catalyst or strong oxidant and does not
      need high reaction temperature. Furthermore, the reaction can also be enlarged to
      the gram scale, and the product 3-bromocoumarins can be further applied in the
      synthesis of complex compounds.

PMID- 29022597
TI  - Genetic effects on gene expression across human tissues.
AB  - Characterization of the molecular function of the human genome and its variation
      across individuals is essential for identifying the cellular mechanisms that
      underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx)
      project aims to characterize variation in gene expression levels across
      individuals and diverse tissues of the human body, many of which are not easily
      accessible. Here we describe genetic effects on gene expression levels across 44
      human tissues. We find that local genetic variation affects gene expression
      levels for the majority of genes, and we further identify inter-chromosomal
      genetic effects for 93 genes and 112 loci. On the basis of the identified genetic
      effects, we characterize patterns of tissue specificity, compare local and distal
      effects, and evaluate the functional properties of the genetic effects. We also
      demonstrate that multi-tissue, multi-individual data can be used to identify
      genes and pathways affected by human disease-associated variation, enabling a
      mechanistic interpretation of gene regulation and the genetic basis of disease.

PMID- 29022620
TI  - Transferring mixtures of chemicals from sediment to a bioassay using silicone
      based passive sampling and dosing.
AB  - Environmental mixtures of chemicals consist of a countless number of compounds
      with unknown identity and quantity. Yet, chemical regulation is mainly built
      around the assessment of single chemicals. Existing frameworks for assessing the
      toxicity of mixtures require that both the chemical composition and quantity are
      known. Quantitative analyses of the chemical composition of environmental
      mixtures are however extremely challenging and resource-demanding. Bioassays may
      therefore serve as a useful approach for investigating the combined toxicity of
      environmental mixtures of chemicals in a cost-efficient and holistic manner. In
      this study, an unknown environmental mixture of bioavailable semi-hydrophobic to
      hydrophobic chemicals was sampled from a contaminated sediment in a coastal
      Baltic Sea area using silicone polydimethylsiloxane (PDMS) as an equilibrium
      passive sampler. The chemical mixture was transferred to a PDMS-based passive
      dosing system, and its applicability was demonstrated using green algae
      Tetraselmis suecica in a cell viability assay. The proportion of dead cells
      increased significantly with increasing exposure level and in a dose-response
      manner. At an ambient concentration, the proportion of dead cells in the
      population was nearly doubled compared to the control; however, the difference
      was non-significant due to high inter-replicate variability and a low number of
      replicates. The validation of the test system regarding equilibrium sampling,
      loading efficiency into the passive dosing polymer, stability of the mixture
      composition, and low algal mortality in control treatments demonstrates that
      combining equilibrium passive sampling and passive dosing is a promising tool for
      investigating the toxicity of bioavailable semi-hydrophobic and hydrophobic
      chemicals in complex environmental mixtures.

PMID- 29022621
TI  - Structural rationale for the chiral separation and migration order reversal of
      clenpenterol enantiomers in capillary electrophoresis using two different beta
      cyclodextrins.
AB  - NMR spectroscopy experiments, molecular dynamics simulations, and theoretical
      chemistry calculations provide insight into the structural and energetic
      determinants of the distinct binding of clenpenterol enantiomers to two
      cyclodextrins and the migration order reversal of their respective inclusion
      complexes in capillary electrophoresis.

PMID- 29022622
TI  - Energy storage properties and relaxor behavior of lead-free Ba1
      xSm2x/3Zr0.15Ti0.85O3 ceramics.
AB  - Lead-free Ba1-xSm2x/3Zr0.15Ti0.85O3 (BSZT) ceramics were synthesized by a solid
      state reaction route. The microstructure, dielectric relaxor behavior and energy
      storage properties of BSZT ceramics were studied. The growth of grain size was
      suppressed with the increase of Sm addition and kept in the submicrometer scale.
      Successive substitution of Sm3+ for Ba2+ disrupted the long-range dipole and
      promoted the increase of polar nano-region (PNR) size, resulting in the enhanced
      degree of relaxor behavior. The increasing PNR size also lead to the slimmer
      hysteresis loops and improved the energy storage efficiency. Furthermore, high
      saturated polarization (Pmax) and low remnant polarization (Pr) were obtained due
      to the formation of defect dipoles, which facilitated the switch of PNRs and
      contributed to the enhancement of energy storage density. The x = 0.003 sample
      was found to exhibit a higher energy storage density of 1.15 J cm-3 and an energy
      storage efficiency of 92%. The result revealed that the BSZT ceramics may be a
      good candidate for energy storage application.

PMID- 29022624
TI  - Prediction of drug-pathway interaction pairs with a disease-combined LSA-PU-KNN
      method.
AB  - Prediction of new associations between drugs and targeting pathways can provide
      valuable clues for drug discovery & development. However, information integration
      and a class-imbalance problem are important challenges for available prediction
      methods. This paper proposes a prediction of potential associations between drugs
      and pathways based on a disease-related LSA-PU-KNN method. Firstly, we built a
      drug-disease-pathway network and combined the drug-disease and pathway-disease
      features obtained by different types of feature profiles. Then we applied a
      latent semantic analysis (LSA) method to perform dimension reduction by combining
      positive-unlabeled (PU) learning and k nearest neighbors (KNN) method. The
      experimental results showed that our method can achieve a higher AUC (the area
      under the ROC curve) and AUPR (the area under the PR curve) than other typical
      methods. Furthermore, some interesting drug-pathway interaction pairs were
      identified and validated.

PMID- 29022628
TI  - Diversity-driven and facile 1,3-dipolar cycloaddition to access dispirooxindole
      imidazolidine scaffolds.
AB  - A diversity-driven three-component 1,3-dipolar cycloaddition of isatins, amino
      acids and isatin-derived ketimines was developed to facilely assemble
      dispirooxindole-imidazolidine skeletons bearing vicinal quaternary carbon
      centers. This protocol features additive-free, minimal solvent usage (0.1 mL
      DMSO/0.2 mmol scale), wide substrate scope (34 examples), mild reaction
      conditions (room temperature) and high chemical yield (up to 99%).

PMID- 29022630
TI  - Evidence of single electron transfer from the enolate anion of an N,N'
      dialkyldiketopiperazine additive in BHAS coupling reactions.
AB  - A designed N,N'-dialkyldiketopiperazine (DKP) provides evidence for the role of
      DKP additives as initiators that act by electron transfer in base-induced
      homolytic aromatic substitution reactions, involving coupling of haloarenes to
      arenes.

PMID- 29022631
TI  - Pd-Catalyzed C-H arylation of pyridazine-based fused 1,2,4-triazoles: overriding
      selectivity at the usual position by undermining of preferred chelate formation.
AB  - The applicability of C-H functionalization to medicinally important 2-pyridyl
      based N-heterocycles suffers from severe challenges owing to the high Lewis
      basicity of the N-atom. This arrests catalytic activity and yields undesirable
      positional selectivity due to preferential chelate formation. In this regard, we
      report a novel palladium(ii)-catalyzed arylation strategy on multiple-N
      containing pyridazines by over-riding the functionalization due to a chelated
      palladacycle. We report a regioselective mono-arylation at the 8-position of
      diphenyl azolopyridazines without any ortho-C-H activation on the proximal phenyl
      groups. This methodology presents a broad arylation scope with uncompromised
      yield and positional selectivity, including the heteroarylation of N
      heterocycles, which is an unprecedented feat for these types of molecules.

PMID- 29022633
TI  - In-site encapsulating gold "nanowires" into hemin-coupled protein scaffolds
      through biomimetic assembly towards the nanocomposites with strong catalysis,
      electrocatalysis, and fluorescence properties.
AB  - An efficient and green biomimetic assembly protocol was developed for the
      fabrication of multifunctional nanocomposites by mimicking the configuration of
      natural protein enzymes. Bovine serum albumin (BSA) as the protein model was
      first split to produce the disassembled BSA (dBSA) of linear polymer and then
      coupled with catalytic Hemin (Hem). The yielded dBSA-Hem scaffolds were utilized
      to in-site encapsulate gold nanoclusters (AuNCs) through biominerization,
      yielding the dBSA-Hem-AuNCs. It was discovered that the nanocomposites could
      display the well-defined composition and spheric morphology. In particular, they
      could exhibit unexpectedly strong catalysis, electrocatalysis, and fluorescence
      properties, in which the biominerized AuNCs would act as fluorescence sources and
      "nanowires" for promoting the electron-transfer of the catalytic nanocomposites.
      Colorimetric investigations show that the developed enzyme mimics could present
      peroxidase-like catalysis activities comparable to natural horseradish
      peroxidase. In addition, they could facilitate the direct electrocatalysis for
      H2O2 at concentrations as low as 0.40 MUM. Moreover, strong red fluorescence of
      AuNCs in nanocomposites could be expected for the fluorimetric analysis of H2O2
      with linear concentrations ranging from 50 nM to 100 MUM. Such a biomimetic
      assembly route may open a new door toward the preparation of diverse
      nanocomposites with multifunctional catalysis and fluorescence, thus promising
      extensive applications of catalysis and detection in the chemical, environmental,
      and biomedical fields.

PMID- 29022634
TI  - The anti-inflammatory effect of Agaricus brasiliensis is partly due to its
      linoleic acid content.
AB  - For hundreds of years mushrooms have been used as functional food for health. The
      basidiomycete Agaricus brasiliensis (A. brasiliensis) is famous for the medicinal
      properties of its beta glucans and of its antioxidants. Most researchers have
      studied polysaccharides from A. brasiliensis for their anti-inflammatory
      activity. However, active compounds from this mushroom have not yet been studied
      for the inactivation of NO inhibitory activity. The present study aimed to find
      the active compounds from A. brasiliensis for their NO inhibitory activity
      related inflammatory activity. This study found that linoleic acid isolated from
      A. brasiliensis inhibited NO production and suppressed the expression of pro
      inflammatory cytokines including TNF-alpha, IL-6, IL-1beta, and NOS2 in RAW 264.7
      cells. Linoleic acid also suppressed the expression of NF-kappaB subunit p50 and
      restored PPARalpha. This leads to the conclusion that linoleic acid from A.
      brasiliensis could reduce NO production and inflammatory activity in RAW 264.7
      cells by the inhibition of p50 and via the activation of PPARalpha. This study
      suggests that linoleic acid present in A. brasiliensis could play a role in the
      prevention of inflammatory diseases for which this edible mushroom is already
      known.

PMID- 29022635
TI  - Bronsted-base-catalyzed remote cascade reactivity of 2,4-dienones - asymmetric
      synthesis of tetrahydrothiophenes.
AB  - This study demonstrates that the remote cascade functionalization of 2,4-dienones
      can be realized by employing Bronsted base catalysis. The developed cascade
      involving 1,6-addition followed by the intramolecular aldol reaction provides a
      straightforward access to polysubstituted tetrahydrothiophene derivatives of
      biological and synthetic importance. Target products, bearing three contiguous
      stereocenters including one quaternary, have been obtained with excellent yields
      (up to 98%) and with good to high stereocontrol (>20 : 1 dr, up to 97 : 3 er)
      with the reaction cascade being promoted by a simple and readily available
      cinchona alkaloid cinchonine.

PMID- 29022636
TI  - The effect of anthocyanins from red wine and blackberry on the integrity of a
      keratinocyte model using ECIS.
AB  - There is a growing market demand for the incorporation of plant-derived
      ingredients into new products for the cosmetic industry. Anthocyanins are
      polyphenols arising from plant secondary metabolism that have been shown to
      possess many bioactive properties such as free radical scavenging, antimicrobial,
      and chemopreventive activities. In this work, the biological activities of red
      wine and blackberry anthocyanins were assessed by developing a new keratinocyte
      barrier model using the HaCat cell line and a microelectrode-based biosensor
      device, referred to as Electric Cell-Substrate Impedance Sensing (ECIS). Cells
      were seeded at the optimal cellular density of 1.6 * 106 cells per mL and the
      half-time was calculated to be 3.55 +/- 0.67 hours. The compounds' cytotoxicity
      was assessed and anthocyanin pigments showed no cytotoxicity towards keratinocyte
      cells. Wound healing assays were also performed using ECIS and it was observed
      that the tested pigments enhanced the healing rate of keratinocyte cells by
      reducing the healing time more than 50%. Cyanidin-3-glucoside presented the best
      results recovering 50% of the injured area in 1.48(+/-0.15) hours, followed by
      the blackberry anthocyanins (2.01 +/- 0.18 hours), malvidin-3-glucoside (2.03 +/-
      0.09 hours) and red wine anthocyanins (2.36 +/- 0.76 hours). All presented
      significant differences from the control 4.91(+/-1.11) hours.

PMID- 29022637
TI  - Coupled swelling and nematic reordering in liquid crystal gels.
AB  - We derive a multiphysics model that accounts for network elasticity with
      spontaneous strains, swelling and nematic interactions in liquid crystal gels
      (LCGs). We discuss the coupling among the various physical mechanisms, with
      particular reference to the effects of nematic interactions on chemical
      equilibrium and that of swelling on the nematic-isotropic transition. Building
      upon this discussion and using numerical simulations, we explore the transient
      phenomena involving concurrent swelling and phase transition in LCGs subject to a
      temperature change. Specifically, we demonstrate separation in time scales
      between solvent uptake and phase change, in agreement with experiments, which
      determines a kinetic decoupling between shape and volume changes. Finally, we
      discuss possible applications in the context of microswimmers, where such a
      kinetic decoupling is exploited to achieve non-reciprocal actuation and net
      motion in Stokes flow.

PMID- 29022638
TI  - Preparation and RGB upconversion optic properties of transparent anti
      counterfeiting films.
AB  - Advanced anti-counterfeiting labels have aroused an intensive interest in
      packaging industry to avoid the serious issue of counterfeit. However, the
      preparation and cost of the existing labels associated with the drawbacks,
      including the complex and high-cost equipment, limit the protection of the
      authenticity of goods. Herein, we developed a series of anti-counterfeiting
      labels based on multicolor upconversion micro-particles (UCMPs) inks via
      straightforward and low-cost solutions, including spin-coating, stamping and
      screen printing. The UCMPs were synthesized through a facile hydrothermal process
      and displayed tunable red (R), green (G) and blue (B) color by doping different
      lanthanide ions, which are Er3+/Tm3+, Yb3+/Er3+ and Yb3+/Tm3+ in NaYF4 hosts,
      respectively. The optimal UCMPs inks were deposited on a flexible polyethylene
      terephthalate (PET) substrate to obtain transparent anti-counterfeiting labels
      possessing higher transmittance, stronger upconversion fluorescence intensity and
      good photostability. Under ambient conditions, the patterns and films were
      transparent, but could exhibit multicolor light under 980 nm laser excitation.
      They can be used as anti-counterfeiting labels for die-cutting packages to
      further elevate the security of goods. The tunable and designable transparent
      anti-counterfeiting labels based on RGB UCMPs inks exhibit the merits of low
      cost, easy-manufacture and versatility, underlying the practical application in
      the field of anti-counterfeiting.

PMID- 29022639
TI  - Glucose oxidase and polyacrylic acid based water swellable enzyme-polymer
      conjugates for promoting glucose detection.
AB  - Glucose oxidase (GOx) and polyacrylic acid (PAA) based water swellable non-toxic
      enzyme-polymer conjugate (PAA-GOx) was immobilized on a substrate consisting of
      graphene oxide (GO) and polyethyleneimine (PEI) (GO-PEI) and the electrochemical
      performances of the new catalyst were investigated. According to the
      measurements, although the amount of GOx immobilized on PAA-GOx was lower than
      that on glutaraldehyde (GA)-GOx, which is a conventionally used conjugate, its
      catalytic activity was 9.6 times higher than that of GA-GOx. The superior
      catalytic activity (102.0 MUA cm-2, 20 mM of glucose) and glucose sensitivity
      (6.9 MUA cm-2 mM-1) were due to its high swellability in water. Due to this, the
      PAA-GOx absorbs a large amount of aqueous glucose molecules and rapidly transfers
      them to the active site of GOx. Desirable hydrogen peroxide and glucose oxidation
      reactions are accordingly promoted. In addition, since PAA has abundant free
      carboxylic acid groups, the PAA-GOx forms covalent bonds with the GO-PEI to
      curtail the leaching-out of GOx molecules.

PMID- 29022640
TI  - Local conformational changes in the 8-17 deoxyribozyme core induced by activating
      and inactivating divalent metal ions.
AB  - The 8-17 deoxyribozyme (DNAzyme) is a catalytic DNA molecule capable of cleaving
      specific RNA substrates. The deoxyribozyme is activated by a wide variety of
      divalent metal ions, from Mg2+ to Pb2+, with just a few exceptions. It is not
      clear if metal ions are directly involved in catalysis, or are required to attain
      an active conformation, or both. In particular, the connection between metal
      induced global structural rearrangements and catalysis is not straightforward. To
      gain more information on the local structural changes induced by metal ions, we
      introduced fluorescent 2-aminopurine (2-Ap) residues at different positions of
      the 8-17 'core'. We found that a construct containing 2-Ap at position 15 was
      best suited to monitor conformational changes in the presence of Mg2+, Ca2+ or
      Mn2+. Binding of these activating metal ions caused a local rearrangement at
      position 15, apparently entailing decreased stacking of the 2-Ap base. The metal
      dependence for such conformational change was generally hyperbolic (suggesting it
      mirrored the binding by a single metal ion) and yielded apparent dissociation
      constants close to those required for activation. In contrast, Cu2+, a divalent
      metal ion which does not support catalysis, caused in the deoxyribozyme a slow,
      reversible inactivation, which correlated with a very distinct conformational
      change at position 15.

PMID- 29022641
TI  - Familial isolated pituitary adenomas (FIPA). Case report of four families and
      review of literature.
AB  - : Background The majority of pituitary adenomas are sporadic, but about 5% of
      them occur in a familial setting, predominantly in multiple endocrine neoplasia
      type 1 and Carney complex. Familial isolated pituitary adenomas (FIPA), unrelated
      to the syndromes mentioned above, were also described. The clinical course of
      FIPA differs significantly from sporadic cases, and is characterized by a larger
      tumor size, more aggressive course and younger patients' age at the moment of
      recognition. Objectives The aim of this retrospective study is to present 4
      families in which two closely related people were diagnosed with pituitary
      adenomas. Probably these cases are clinical manifestations of FIPA. Material and
      methods Eight patients within four families, presenting with anterior pituitary
      tumors were described. The authors analyzed medical and family histories of the
      patients, their imaging pictures (pituitary MRI/CT) and hormonal tests. Results
      Family 1.: two sisters with acromegaly in the course of macroadenoma. Family 2.:
      two brothers with clinically nonsecreting macroadenomas. Family 3.: father and
      daughter with clinically nonsecreting macroadenomas. Family 4.: young man with
      acromegaly caused by macroadenoma and a daughter of his mother's sister with
      microprolactinoma. CONCLUSIONS: Familial isolated pituitary adenomas are more
      common than it was previously thought, therefore, specific questioning regarding
      family history should be a part of the workup of all patients with pituitary
      adenomas. Genetically induced pituitary tumors often have aggressive behavior in
      terms of tumor expansion and resistance to different treatment options and often
      involve a multidisciplinary approach that combines endocrine, neurosurgical, and
      radiological specialists.

PMID- 29022642
TI  - Induction of puberty with human chorionic gonadotropin (hCG) followed by reversal
      of hypogonadotropic hypogonadism in Kallmann syndrome.
AB  - INTRODUCTION: Kallmann syndrome (KS) is a rare, congenital disorder combining
      hypogonadotropic hypogonadism (HH) due to GnRH-deficiency with anosmia.
      Traditionally thought to require lifelong therapy it turns out to be a reversible
      condition in some patients. CASE REPORT: We present a case of a 22-year old man
      with absent puberty due to KS, in whom genetic testing revealed heterozygosity
      for a mutation in the PROK2 gene. Pubertal development and virilisation was
      achieved by using human chorionic gonadotropin (hCG) injections followed by
      testosterone replacement. During the follow-up we observed reversal of
      hypogonadism allowing discontinuation of testosterone treatment. Normalisation of
      testicular volume as well as gonadotropin and inhibin B levels through a 2-year
      postreversal period was seen. CONCLUSIONS: Treatment with hCG is effective in
      inducing pubertal development and may have advantage over testosterone
      replacement due to a potential of gonadal maturation. A regular assessment of
      testicular volume and biochemical surveillance including measuring of serum
      inhibin B and gonadotropins are necessary for a timely detection of reversal of
      GnRH deficiency.

PMID- 29022643
TI  - The efficiency of elastography in the diagnostics of follicular lesions and
      nodules with an unequivocal FNA result.
AB  - INTRODUCTION: The aim was to assess the usefulness of strain elastography (SEG)
      in the diagnostics of two groups of thyroid nodules (TNs): follicular lesions
      (FL) with low malignancy risk (< 20.0%) and low percentage of papillary
      carcinomas (PTCs) among cancers as well as TNs with unequivocal cytology (UC) and
      high percentage of PTCs among cancers. MATERIAL AND METHODS: 168 TNs were
      analysed and eventually surgically treated: 100 UC (50 benign and 50 malignant -
      90.0% PTCs) and 68 FL (60 benign, 8 malignant - 50.0% PTCs). Elasticity score
      (ES) and strain ratio (SR) were evaluated, and their effectiveness was compared
      with the evaluation of the number of ultrasound malignancy risk features
      (NoUMRFs). RESULTS: In the UC group the evaluation of mean values of SR and ES in
      both sections (meanSR, meanES) was more efficient than NoUMRFs analysis (AUC:
      0.903 and 0.869 vs. 0.754, p < 0.05). The following thresholds: meanSR >= 2.01,
      meanES >= 2.5, NoUMRFs >= 2, were related to the increased malignancy risk in
      nodules (OR: 45.0; 23.2; 5.4, respectively), but only meanSR >= 2.01 was an
      independent risk factor (OR: 20.3; SEN: 86.0%, SPC: 88.0%). In the FL group, only
      the evaluation of tSR (SR assessed in transverse section) had the value of AUC >
      0.7, and only the set of features: tSR >= 1.7 and NoUMRFs >= 1 increased the
      malignancy risk in nodules (OR: 12.0; SEN: 75.0%, SPC: 75.0%). CONCLUSIONS: SEG
      is more reliable than conventional US in the diagnostics of TNs. The efficacy of
      SEG decreases with lowering percentage of PTCs among cancers. But in FL nodules
      SEG may support the selection of nodules for surgical treatment.

PMID- 29022644
TI  - Assessment of risk factors in metastatic/recurrent tall cell variant of papillary
      thyroid carcinoma.
AB  - INTRODUCTION: Papillary thyroid carcinoma (PTC) is the most common malignant
      thyroid tumor. A great majority of the cases live a disease-free life with quite
      favorable prognosis. There are lots of variants of PTC and a few of them exhibit
      aggressive behaviour. Typical example is the tall cell variant (TCV). Patients
      experience a greater incidence of recurrence, nodal and extranodal metastases,
      tumor associated mortality than other variants of PTC. Studies related to TCV
      almost always compared it with its patient population of PTC according to risk
      factors and clinicopathologic features. The aim of this study is to evaluate the
      risk factors in metastatic/recurrent TCV. MATERIALS AND METHODS: This is a
      retrospective cohort study of 1813 patients with differentiated thyroid carcinoma
      treated with radioiodine between 1992 and 2011. 56 of these patients are TCV. 34
      of them developed metastasis/recurrence and 22 lived a disease-free life during
      the 23-year follow-up. We evaluated the risk factors in these metastatic and
      nonmetastatic subgroups. RESULTS: We found tumor size, preablation thyroglobulin
      level, vascular invasion, preablation central and lateral cervical lymph node
      metastasis, preablation lung metastasis and stage independent risk factors.
      However age, preablation thyroglobulin level and stage appeared together as
      striking factors impacting metastasis in multivariate analysis. CONCLUSION:
      Higher ablation doses up to 250-300 mCi should be administered to TCV patients
      having advanced stage (III,IV), pretty high preablation thyroglobulin level (over
      400 ng/ml) and older age (over 52 years) especially with large tumor size (over
      3.5 cm) and initial cervical lymph node metastasis.

PMID- 29022645
TI  - The significance of TRIP11 and T3 signalling pathway in renal cancer progression
      and survival of patients.
AB  - INTRODUCTION: TRIP11 is a multifunctional protein localizing either to Golgi
      apparatus, acting as a golgin, or in the nucleus, acting as coactivator of
      transcription mediated by thyroid hormone receptor (THR) and hypoxia induced
      factor (HIF). Triiodothyronine (T3) regulates nuclear localization of TRIP11 by
      inducing its phosphorylation. The exact mechanism of this regulation unknown. The
      expressions of THR and HIF are disturbed in various cancers, including renal cell
      cancer (RCC). In this study we aimed to analyze: 1) the mechanism of T3-dependent
      subcellular localization of TRIP11; 2) the significance of TRIP11 and T3
      signaling pathway in RCC progression. MATERIAL AND METHODS: TRIP11 subcellular
      localization was analyzed using immunocytochemistry in RCC-derived cell line
      treated with T3, T3-agarose and PI3K inhibitor, wortmannin. The expressions of
      TRIP11 and genes involved in T3 signaling and hypoxia were investigated using
      qPRC in 36 pairs of RCC tumor-control samples, followed by validation/survival
      analysis in an independent cohort of >450 renal cancer patients. RESULTS:
      Wortmannin disrupted T3-dependent nuclear transport of TRIP11. T3-agarose did not
      change TRIP11 localization, precluding extracellular T3-mediated mechanism. The
      expressions of TRIP11, HIF-1beta, THRA, THRB, FURIN, VEGFA, and GLUT1 were
      disturbed in renal cancer. Expressions of TRIP11 and HIF-1beta correlated with
      tumor grades. Decreased expressions of TRIP11, THRA, and THRB correlated with
      poor survival of RCC patients. CONCLUSIONS: 1) T3 induces nuclear TRIP11
      localization via PI3K-dependent mechanism; 2) disturbed expression of T3
      signaling pathway genes correlates with RCC progression. The specific mechanisms
      by which altered T3 signaling may contribute to RCC progression require further
      investigation.

PMID- 29022646
TI  - Low skeletal mass is an important predictor of osteoporosis in HIV-infected men
      in India.
AB  - INTRODUCTION: This study evaluated prevalence and predictors of osteoporosis and
      sarcopenia in men with HIV. MATERIAL AND METHODS: 220 men with HIV were screened,
      of which 115 men, 30-50 years-age, having at least 1-year follow-up, underwent
      hormonal and DEXA analysis. 40 controls were also evaluated. RESULTS: Males with
      HIV had significantly lower BMD and Z-scores at all sites. Osteoporosis was
      diagnosed in 64.35%; commonest site being radius total (49.56%), followed by
      radius 33% (45.21%), radius ultra distal (36.52%), lumbar spine (19.13%), neck of
      femur (17.39%), total femur and greater trochanter (7.82% each). HIV patients had
      significantly lower fat mass (FM), lean mass (LM), total fat percent, bone
      mineral content, gynoid fat, percent skeletal muscle mass (PSMM). Men with
      osteoporosis had higher use of anti retroviral therapy (ART), immune
      reconstitution inflammatory syndrome (IRIS), tuberculosis, lower FM, LM and PSMM.
      Logistic regression revealed PSMM, age and delta (Delta) CD4 count (change in CD4
      count after 6-12 months of ART, compared to pre-ART) were best predictors of
      osteoporosis. Greater PSMM was associated with decreased osteoporosis, without
      adjusting for any variable (Model-1), adjusting for disease duration,
      tuberculosis and IRIS (Model-2), and model-2 plus gonadotropins and sex steroids
      (Model-3). Greater DeltaCD4 count and age were associated with increased
      osteoporosis after adjusting for different models. Sarcopenia was observed in 40%
      men and none in controls. CONCLUSIONS: Men with decreased skeletal mass, age,
      severe immune dysfunction at diagnosis, having rapid increase in CD4 count
      following ART and IRIS have higher risk of osteoporosis in the long run.

PMID- 29022647
TI  - Use of metformin is associated with lower incidence of cancer in patients with
      type 2 diabetes.
AB  - INTRODUCTION: The objective of the study was to assess the influence of metformin
      on the prevalence of cancer and risk factors for the development of cancer, in
      patients with type 2 diabetes. MATERIALS AND METHODS: A total of 1063 patients,
      treated between October 2012 and March 2013 in the Diabetes and Endocrinology
      Centre in Bydgoszcz, were enrolled in the study. Only patients who were first
      diagnosed with diabetes and consecutively with cancer were included in the
      analysis. The final dataset compromised data from 1028 patients with type 2
      diabetes, in whom retrospective analysis of the association between the
      occurrence of cancer and treatment with or without metformin was performed.
      Demographic data, medical history, physical assessment, diabetes history,
      diabetes complications, concomitant medication, and additional examination
      results were compared between two groups: those with cancer and those without
      cancer. Data were analysed using Student's t-test, Chi-square test with Yates'
      continuity correction, and multiple logistic regression. RESULTS: The most
      commonly observed cancer was breast cancer (24 patients; 22.5%), followed by
      uterine cancer (15 patients; 13.6%). Of the 75 diabetic patients with a cancer
      diagnosis, 18.7% were treated with metformin; of the 953 patients without cancer,
      38% received metformin. Analysis of probability of cancer occurrence using Kaplan
      Meier curves showed that the probability of cancer development was higher in
      groups of patients who were not treated with metformin (p = 0.006). CONCLUSIONS:
      Metformin treatment reduces the risk of cancer in type 2 diabetes patients.

PMID- 29022648
TI  - Probiotics for experimental obesity prevention: focus on strain dependence and
      viability of composition.
AB  - INTRODUCTION: a comparative animal study of the efficacy of intermittent short
      course administration of lyophilised single-, three-, and live multistrain
      probiotic on obesity. METHODS: We included 70 rats divided into seven groups (n =
      10 in each). Rats of group I were intact. Newborn rats of groups II-VII were
      injected with monosodium glutamate (MSG) (4 mg/g). Rats of group II (MSG-obesity
      group) were untreated. The group III-V received lyophilised monoprobiotics B.
      animalis VKL, B. animalis VKB, and L. casei IMVB-7280, respectively. Group VI
      received the mix of these three probiotic strains. Group VII was treated with
      multiprobiotic "Symbiter", which contains 14 live probiotic strains
      (Lactobacillus, Bifi-dobacterium, Propionibacterium, Acetobacter genera).
      RESULTS: Neonatal treatment with MSG caused stunted growth, which is why, despite
      the lack of weight gain dynamics and absence of significant food consumption rate
      and body weight changes at day 120, we noted the development of obesity in all
      MSG-obesity rats and in up to 20-70% after probiotic administration.
      Supplementation of probiotic composition, with preference to live strains, led to
      a significantly lower prevalence of obesity, and reduction of VAT weight and
      serum lipid levels as compared to single-strain probiotic. In our comparative
      single-strain analysis a trend towards more pronounced hypolipidaemic effect and
      VAT weight reduction was observed for lyophilised L. casei IMVB-7280 as compared
      to B. animalis VKL and VKB strains. CONCLUSIONS: Multistrain formed mutualistic
      interactions in mixtures and therefore able to share with different metabolites,
      affect differ-ent receptors and produced various of biologically active compounds
      which synergistic overall effect greater than the sum of the single effects.

PMID- 29022649
TI  - The quality of semen among a sample of young, healthy men from Lower Silesia
      (AndroLS).
AB  - INTRODUCTION: Contrary to other parts of the continent, little information is
      available regarding semen quality among subjects from central and eastern Europe.
      MATERIAL AND METHODS: We evaluated semen profiles among a sample of men from an
      industrialised region of Poland. We directly invited 5000 healthy inhabitants of
      the region (aged 18-35 years; with unchecked fecundity) to participate in the
      study. Among the 500 who were eligible and willing to participate, we acquired
      detailed information and semen and blood samples from 177 subjects. RESULTS:
      Semen volume, sperm concentration, and total sperm count were, respectively,
      (mean +/- SD): 3.1 +/- 1.5 ml, 60 +/- 44 x 106/ml and 170 +/- 137 x 106/ml.
      Percentage of normal forms was 14.7 +/- 6.5%. CONCLUSIONS: Due to the relatively
      low sperm motility (mean +/- SD: 54 +/- 16%) and vitality (mean +/- SD: 60 +/-
      15%) values, these variables require special attention during routine
      evaluations. The WHO 2010 criteria for these two parameters were met in only 60%
      and 66% of the samples, respectively. Further studies on men with different
      educational levels, social environments, or living conditions are needed to
      confirm our results.

PMID- 29022650
TI  - Sleep-related breathing disorders in patients with Prader-Willi syndrome
      depending on the period of growth hormone treatment.
AB  - INTRODUCTION: Sleep-related breathing disorders (SRBD) are commonly present in
      patients with Prader-Willi syndrome (PWS). Recombinant human growth hormone
      (rhGH) treatment is reported to improve breathing function in PWS, but the
      findings are not explicit. MATERIAL AND METHODS: Screening polysomnography-
      polygraphy (PSG), assessing nasal respiratory flow, respiratory effort, and blood
      oxygen saturation, was used. Group 1 - before rhGH therapy (n = 11, mean age 3.0
      years); PSG was repeated after the start of rhGH therapy in a mean time of 0.9
      years in six patients (Group 1a). Group 2 - on rhGH treatment, for a mean time of
      four years (n = 17, mean age 8.8 years). Group 3 - without rhGH therapy due to
      severe obesity (n = 8, mean age 13.1 years). RESULTS: Group 1 - mean apnoea
      hypopnoea index (AHI) was 10.2, oxygen desaturation index (ODI)- 36.3, Group 1a-
      AHI 12.0, ODI 60.9, Group 2-AHI 9.0, ODI 25.1, Group 3- AHI 8.2, ODI 22.0. ODI
      was significantly higher in Group 1a than in the other groups (p < 0.005), but
      not strictly related to SRBD. The results in Group 2 did not differ significantly
      from those of Group 1. CONCLUSIONS: Our study proves the high frequency of SRBD
      among PWS patients, with worsening of ODI after short-term rhGH therapy.

PMID- 29022653
TI  - Dr Dodds Replies. Benzodiazepines Do Not Cause Suicide or Suicide Attempts

PMID- 29022652
TI  - Benzodiazepines Do Not Cause Suicide or Suicide Attempts.

PMID- 29022654
TI  - Epidemiology, Prevention, and Assessment of Tardive Dyskinesia and Advances in
      Treatment.
AB  - Tardive dyskinesia (TD) is a disorder characterized by involuntary movements,
      typically of the orofacial muscles and also of the extremities and other muscle
      groups. The condition is associated with exposure to dopamine receptor blocking
      agents, including antipsychotics. Because the indications and off-label uses for
      these agents have expanded over the last 2 decades, a larger number of patients
      are receiving antipsychotic medications than in the past. While evidence suggests
      that patients being treated with second-generation antipsychotics have less risk
      for developing TD than those treated with first-generation antipsychotics, the
      decreased risk is not as great as was originally expected. In addition, patients
      with chronic psychiatric conditions often require long-term use of
      antipsychotics, putting them at risk for TD. This article addresses the
      prevalence, risk factors, and prevention of TD; assessment strategies including
      diagnostic criteria and rating scales; and evidence for TD treatments, including
      2 newly approved medications: deutetrabenazine and valbenazine. .

PMID- 29022656
TI  - ?

PMID- 29022657
TI  - [Shortening the antibiotherapy is in progress: get up to date!]
AB  - In a world where the emergence of resistant bacteria threatens the future use of
      many antibiotics, it is now critical to prescribe antibiotics carefully in order
      to minimize selective pressure. Limiting treatment duration would be one of the
      strategies to achieve this goal. Recent studies state that a reduction of the
      course of treatment is showing great benefit with no outcome difference.

PMID- 29022655
TI  - Anosognosia Is an Independent Predictor of Conversion From Mild Cognitive
      Impairment to Alzheimer's Disease and Is Associated With Reduced Brain
      Metabolism.
AB  - OBJECTIVE: Anosognosia, or impaired illness awareness, is a common feature of
      Alzheimer's disease (AD) and less so of mild cognitive impairment (MCI).
      Importantly, anosognosia negatively influences clinical outcomes for patients and
      their caregivers and may predict the conversion from MCI to AD. This study aimed
      to examine (1) the relationship between brain glucose metabolism as measured by
      fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and
      anosognosia in patients with MCI and AD and (2) the predictive utility of
      anosognosia in patients with MCI for later conversion to AD, even when
      controlling for other factors, including gender, education, apolipoprotein E
      epsilon4 carrier status, dementia severity, and cognitive dysfunction. METHODS:
      Data for 1,062 participants from the Alzheimer's Disease Neuroimaging Initiative
      database (2003 to August 2015) classified as having AD (n = 191) or MCI (n = 499)
      or as healthy comparison (HC) subjects (n = 372) were analyzed. HC participants
      had Mini-Mental State Examination (MMSE) scores from 24 to 30 and a Clinical
      Dementia Rating (CDR) of 0. MCI participants had MMSE scores from 24 to 30, a
      memory complaint, objective memory loss, a CDR of 0.5, absence of significant
      levels of impairment in other cognitive domains, and essentially preserved
      activities of daily living. AD participants had MMSE scores <= 26 and a CDR of >=
      0.5, and met National Institute of Neurological and Communicative Disorders and
      Stroke-Alzheimer's Disease and Related Disorders Association criteria for
      probable AD. Anosognosia was measured with the composite discrepancy score of the
      study partner and participants' scores on the Everyday Cognition scale (ECog).
      Bivariate correlations and multiple regression analyses were performed to assess
      the relationship between anosognosia and FDG-PET findings in each group. Lastly,
      logistic regression and receiver operating characteristic curve analyses were
      performed in the MCI sample to determine if anosognosia was predictive of
      conversion from MCI to AD. RESULTS: Hypometabolism was independently associated
      with anosognosia in AD, particularly in the posterior cingulate cortex and right
      angular gyrus. Anosognosia was associated with conversion from MCI to AD within 5
      years (OR = 2.74 [95% CI, 1.95 to 3.85], chi21 = 33.65, P < .001), even after
      including covariates (OR = 1.64 [95% CI, 1.12 to 2.40], chi21 = 6.43, P = .011).
      ECog-composite scores <= -0.75 were 93% sensitive and 15% specific for conversion
      from MCI to AD. CONCLUSIONS: Anosognosia in AD is related to brain glucose
      hypometabolism. Further, anosognosia independently predicts conversion from MCI
      to AD. The absence of anosognosia may be clinically useful to identify those
      patients that are unlikely to convert from MCI to AD.

PMID- 29022658
TI  - [Legionellosis].
AB  - Legionellosis refers to the two clinical syndromes caused by Legionella : Pontiac
      fever, a benign febrile illness and Legionnaires'disease (or pneumonia).
      Clinically and radiologically, Legionnaires'disease presents itself as a "
      typical " pneumonia caused by Streptococcus pneumonia. Diagnosis is usually made
      by using urinary antigen testing. Culture and PCR are also helpful. Legionella is
      resistant to betalactam antibiotics, and is treated by quinolones or macrolides.

PMID- 29022659
TI  - [Listeria monocytogenes infections].
AB  - Listeria monocytogenes infections are caused by food ingestion. They are not only
      transmitted by animal products, but also by secondarily contaminated fruits and
      vegetables. They preferentially affect pregnant women, patients of extreme ages
      and the immu-nocompromised, and manifest as a gastroenteritis, bacteremia,
      meningo-encephalitis or maternal-fetal infection. Diagnosis is achieved by
      culture of usually sterile sites. The preferred treatment is amoxicillin with or
      without gentamicin. For patients at risk, prevention is based on avoiding at-risk
      food or cooking it when possible.

PMID- 29022660
TI  - [Food-borne trematodiases].
AB  - Food-borne trematodiases (flukes) are transmitted through the consumption of
      contaminated undercooked aquatic food. Infections are most prevalent in Southeast
      Asia and Latin America, but might occur anywhere due to food trade, international
      travel, human migration. Clinical manifestations are hepatobiliary, intestinal,
      and pleuropulmonary. The worse complication is development of cholangiocarcinoma.
      Efficacious drug therapy are available, however prevention control measures are
      essential to avoid transmission. Since 2015, trematodiases are included in the
      WHO program implemented to fight neglected tropical diseases.

PMID- 29022661
TI  - [Candida in urine: colonization ? Infection ? When and how to treat ?]
AB  - Candida is frequently found in urine cultures. Deciding whether this represents
      simple colonization or true infection is often difficult since Candida is a
      normal genital and urinary tract commensal. Urinary tract colonization is
      facilitated by well identified risk factors. The diagnostic of a true infection
      relies upon the identification of the usual clinical signs which cannot be
      attributed to another pathogen ; also, plasma level of beta-D-glucan can
      contribute to confirm the diagnostic. Treatment success depends upon the
      possibility to correct the risk factors and appropriate anti-fungal therapy
      according to in vitro susceptibility testing.

PMID- 29022662
TI  - [Infectious diseases as you have never read them].
AB  - Infectious diseases is known as a serious medical discipline. Nevertheless some
      experiences related by patients and unusual studies can bring a smile on your
      face. In this article, you will find a sample of rare and original studies in
      this field, extracted from a collection of comical published medical articles.

PMID- 29022663
TI  - ?

PMID- 29022664
TI  - ?

PMID- 29022665
TI  - ?

PMID- 29022666
TI  - ?

PMID- 29022667
TI  - ?

PMID- 29022668
TI  - ?
AB  - This erratum corrects information regarding golimumab in table 6 for article
      [Management of ulcerative colitis in 2017], PMID: 28853805.

PMID- 29022669
TI  - ?

PMID- 29022670
TI  - ?

PMID- 29022671
TI  - Air Pollution and Mortality in the Medicare Population.

PMID- 29022672
TI  - Air Pollution and Mortality in the Medicare Population.

PMID- 29022673
TI  - CD55 Deficiency and Protein-Losing Enteropathy.

PMID- 29022674
TI  - Public Health Crisis: the Need for Primary Prevention in Failed and Fragile
      States.
AB  - OBJECTIVE: A new 'normal' in global affairs may be erupting from large global
      powers to that of non-state actors and proxies committing violence through scaled
      conflict in a post-Westphalian world generating significant global health policy
      challenges. Health security of populations are multifactorial and indirectly
      proportional to war, conflict and disaster. Preventing conflict and avoiding the
      health vacuum that occurs in war and violence may be best practices for policy
      makers. This paper considers an approach of applying clinical primary prevention
      principles to global health policy. METHODS: Brief policy review of current
      standards and practices in health security in fragile and failed states and
      prevention; and definitions discussion. A short case study series are presented
      with best practices, with risk and outcome review. RESULTS: The global balance of
      power and order may be shifting through geopolitical transference and inadequate
      action by major global power brokers. Health security in at risk nation-states
      may be decreasing as a result. CONCLUSION: Small scale conflict with large-scale
      violence threatens health security and may experience increased incidence and
      prevalence in fragile and failed states. Preventative policy to resuscitate
      fragile and failed states and prevent further external and internal shocks may
      support health and promote a positive feedback loop of further state stability
      and increased health security. Public health policy shift to mitigate state
      failure and public health crisis in war and conflict through the basis of primary
      prevention may provide best practices and maximize health security for at risk
      populations.

PMID- 29022675
TI  - The Czech Republic and Slovakia in Terms of Mortality from Malignant Neoplasms:
      Similar or Opposite Tendencies?
AB  - In Europe, a steady mortality decline has been observed from the 1950s, however,
      Central and Eastern Europe underwent a period of stagnation or even worsening
      from the 1960s to 1980s. Since that time an evident mortality decline could be
      observed in that part of Europe too. Within the post-communist countries,
      mortality development has been most favourable in Slovenia, the Czech Republic
      and Slovakia. The aim of this study is to describe the latest development of
      cancer mortality in two selected countries - the Czech Republic and Slovakia.
      These two countries have much in common, including many similar long term trends
      in demographic or social indicators' development. The study evaluates whether
      cancer mortality development differs in the two countries or rather follows a
      similar trend. From the presented results it is clear that the development
      apparently differs namely according to sex. The results according to selected
      particular causes of death (from the group of malignant neoplasms) are presented
      as well. It could be assumed that many aspects could be improved by prevention
      programmes or screening.

PMID- 29022676
TI  - Vitamin D Deficiency in Acute Coronary Syndrome - Clinically Relevant or
      Incidental Finding?
AB  - OBJECTIVE: Vitamin D deficiency has been associated with cardiovascular disease.
      The aim of this study was to determine serum concentration of 25 hydroxyvitamin D
      (25(OH)D) in patients with acute coronary syndrome (ACS) and to assess the
      prognostic role of serum vitamin D level in ACS patients during 3-year follow up.
      METHODS: The study included 60 ACS patients hospitalized at cardiology department
      for ACS between March 2012 and October 2012, and 60 age- and sex-matched control
      patients without ACS. Standard laboratory testing and vitamin D determination
      were performed in all study patients. In addition, ACS patients underwent
      coronarography and were followed-up for 36 months of ACS for major adverse
      cardiac events (MACE). RESULTS: Patients with ACS had a statistically
      significantly lower mean 25(OH)D level as compared with control group (35.19
      nmol/L vs. 58.08 nmol/L, p<0.001). The lowest mean level of 25(OH)D was recorded
      in diabetic patients with ACS (30.45 nmol/L). ACS patients were divided into
      three subgroups according to coronarography findings: single vessel, double
      vessel and triple vessel coronary artery disease (CAD) with respective serum
      levels of 25(OH)D of 36.44 nmol/L, 33.65 nmol/L and 31.70 nmol/L. During 36-month
      follow up, the event-free survival rate was 60% in the ACS group. The ACS
      patients having sustained MACE during follow up had low serum level of 25(OH)D in
      the acute phase; however, the difference from ACS patients without MACE during
      follow up did not reach statistical significance (32.64 nmol/L vs. 37.01 nmol/L).
      CONCLUSIONS: Patients with ACS have low vitamin D level, which is lowest in
      diabetic patients with ACS. However, during 3-year follow up, vitamin D failed to
      prove useful as a prognostic biomarker in ACS patients.

PMID- 29022677
TI  - Alcohol Consumption in Population Aged 25-65 Years Living in the Metropolis of
      South Moravia, Czech Republic.
AB  - OBJECTIVE: The aim of the study was to evaluate alcohol consumption in a
      representative sample of the population of the city of Brno, as part of research
      on cardiovascular risk factors. METHODS: Cross-sectional survey on a sample of
      2,160 randomly selected residents 35-65 years old was carried out. For the
      invited volunteers who became a part of the investigation, alcohol consumption
      was determined in a controlled, face to face interview structured in accordance
      with a special questionnaire form. The frequency of alcohol consumption during
      the previous year was determined, in more detail during the last month (including
      quantification using "units of alcohol", their normal and maximum level of
      drinking, and any association between alcohol consumption and meals), and during
      the last week in the form of a complete, beverage specified and quantified 7-day
      recall period. Typical patterns of alcohol consumption were explored by the means
      of cluster analysis. RESULTS: During the past 12 months, 90.0% of the men and
      79.0% of the women had consumed alcohol, the rest can be considered abstinent.
      The most commonly reported frequency was 2-4 times per week (35.6% of the men),
      or 1-3 times per month (22.8% of the women). Daily or almost daily consumption
      was reported by 24.8% of the men and 12.8% of the women. The number of units of
      alcohol consumed usually on one occasion amounts to an average of 3.88+/-4.80 for
      the men and 2.25+/-1.39 for the women, but the amount most often cited by both
      sexes was 2 drinks (36.4% of the men and 40.4% of the women). The largest amount
      consumed on any occasion during the last 30 days was 5 or more units in 69.3% of
      the men, and in 33.9% of the women it was 4 or more units (this amount of alcohol
      leads to a blood alcohol concentration (BAC) of 0.08, the border of drunkenness).
      In 19.9% of the men and 7.5% of the women, this border was exceeded more than 5
      times in the past month. Only 14.7% of the men and 10.3% of the women reported
      that the majority of their alcohol consumption occurs with food; on the contrary,
      64.3% of the men and 77.6% of the women drinkers drink it either always without
      food or only rarely with it. During the past week, 81.6% of the men and 63.4% of
      the women drank alcohol (p<0.001, chi-square). The average value of consumption
      for one man was 11.57+/-11.91 doses, and for one woman 4.68+/-6.38 doses per week
      (p<0.001, t-test). A total of 17.8% of the men exceeded the limit of 21 doses per
      week, and 7.4% of the women exceeded 14 doses/week. After converting the weekly
      consumption into the number of units of alcohol per week expressed in litres per
      year, the total average consumption was 5.01+/-6.36 litres; for the men 7.26+/
      7.62 litres and for the women 3.02+/-4.08 litres of pure alcohol per person
      annually. Consumption during the week was not uniform (p<0.001, ANOVA), with the
      highest occurring on Saturday, followed by Friday. The men mostly drank beer
      (62.9% of the total volume of alcohol), the women wine (68.6%). The cluster
      analysis identified 5 clusters of respondents, based on a set of alcohol
      consumption variables, as follows: very heavy drinking (1.6% of the respondents
      who drink alcohol); heavy drinking (8.8%); binge drinking (6.3%); moderate
      drinking (31.1%); and occasional drinking (52.3%). CONCLUSIONS: The results show
      a relatively high consumption of alcohol in the examined group. The recommended
      weekly limits were exceeded by only a small portion, but that consumption had a
      binge character. Conversion into a form allowing comparison with conventional
      national statistics shows a significantly lower consumption than these reported
      statements. Overall, men consume significantly more alcohol than women.

PMID- 29022678
TI  - Exposure to Psychoactive Compounds amongst Students of Medical University.
AB  - OBJECTIVE: The aim of this study was to assess the frequency of exposure to
      psychoactive compounds amongst students of the Medical University of Bialystok.
      METHOD: This cross-sectional study included 504 students selected by means of
      stratified sampling based on the university faculty, study discipline and year,
      and participant's gender. RESULTS: Nearly three fourths of our respondents have
      contact with their student colleagues who use psychoactive compounds, or have
      heard that such individuals exist. Approximately one fourth of the students
      declared that they considered using psychoactive compounds at least once.
      Marijuana and hashish were the psychoactive compounds our respondents used most
      frequently. Median age of the first contact with these substances was 18 years.
      Alarmingly high fraction of respondents declared that most of psychoactive
      compounds included in the study is easily available and obtaining them would not
      take them longer than one day. Furthermore, 15% of respondents admitted to being
      involved in the distribution of psychoactive compounds. CONCLUSION: The exposure
      of medical university students to psychoactive compounds represents similar
      problem as in their peers studying other disciplines. However, in view of its
      specific consequences (including potential threat to patients' health and life),
      the problem should not be underestimated.

PMID- 29022679
TI  - Brand Awareness and Access to Cigarettes among Children 8-12 Years Old in the
      Czech Republic.
AB  - OBJECTIVE: The aim of the study is to assess smoking behaviour, knowledge of
      cigarette brands and access to cigarettes among children 8-12 years old in the
      Czech Republic. METHOD: Between 2009 and 2012, a cross sectional survey was
      conducted among 4,439 children aged 8-12 years attending 51 primary schools in
      Prague and Central Bohemia, Czech Republic. Data including age, gender, ever
      smoking, parental and sibling smoking, knowledge of cigarette brands, sources of
      cigarettes, and smoking frequency were collected. RESULTS: Fifty nine percent of
      all children could name one or more cigarette brands, 62.8% of boys and 55.3% of
      girls (p<0.01). The most well-known brands were Marlboro and the local brand
      Petra. Marlboro was better known among boys, while Petra was more known among
      girls. Children whose parents smoke showed higher brand awareness than children
      with non-smoking parents, 72.5% and 45.6%, respectively (p<0.001), and 76.4% of
      children reported one or more possible sources where to obtain cigarettes. Nearly
      one quarter (23.3%) of children had ever tried cigarettes, water pipe, cigars, or
      marijuana. Nearly half of all children (43.1%) reported that they had obtained
      their first cigarette from a relative or at home, and the second most frequent
      source were their peers (22.8%). Only 3.9% of children reported that they had
      purchased their first cigarettes. Relatives were the main source of cigarettes
      among children that reported smoking more than once. CONCLUSIONS: The high level
      of cigarette brand awareness and ever smoking provide evidence that tobacco
      control policies in the Czech Republic do not adequately protect children.
      Tougher legislation and effective strategies in accordance with the WHO Framework
      Convention on Tobacco Control are therefore required to better protect children
      from harmful effects of smoking and the influence of tobacco industry in the
      Czech Republic.

PMID- 29022680
TI  - Patients' Risk of Causing Traffic Violations and Traffic Accidents while Driving.
AB  - OBJECTIVES: This study examines whether drivers suffering from epilepsy, chronic
      alcoholism and/or hazardous drinking, psychoactive substance abuse, other
      diseases of the nervous system, mental and behavioural disorders, cardiovascular
      diseases, severe diabetes, and severe eye diseases are at a greater risk of
      causing traffic accidents and traffic violations than drivers that cause
      accidents and violations without these diagnoses. METHODS: A case control study
      was carried out. The cases were drivers checked by a special medical committee in
      the period observed suffering from the diseases listed above. Matched controls
      were taken from the cohort of those that caused accidents and violations during
      the same period observed. The descriptive statistics were followed by calculation
      of correlations, t-tests and chi2, and the odds ratio. RESULTS: Drivers with
      referrals for diseases of the nervous system are five times more likely to cause
      a traffic accident compared to controls (OR=5.18; 95% CI=2.59-10.34); in
      addition, a high risk is associated with drivers with mental and behavioural
      disorders (OR=3.64; 95% CI=1.91-6.94), drivers with epilepsy (OR=1.99; 95%
      CI=1.01-3.92), and drivers addicted to alcohol (OR=1.71; 95% CI=1.01-2.89).
      CONCLUSION: Drivers suffering from addiction, a disease of the nervous system, or
      epilepsy are more likely to cause a traffic accident, which is a contribution to
      the inconclusive findings of previous studies. The multiple reasons for risks of
      patients suffering from mental and behavioural disorders need to be further
      investigated.

PMID- 29022681
TI  - Body-image Dissatisfaction and Weight-control Behaviour in Slovak Adolescents.
AB  - OBJECTIVES: The aim of the study was to examine body-image dissatisfaction in
      adolescents aged 13-15 years reporting to be on a diet and to assess gender and
      age differences in weight-reduction behaviour in Slovak adolescents. METHODS:
      Data on a representative sample of 2,765 adolescents (mean age 14.37 years) from
      the Slovak part of Health Behaviour in School Aged Children Study carried out in
      2014 were analysed. Self-reported body-image dissatisfaction and engagement in
      weight-reduction behaviour of 13 to 15-year-old adolescents was assessed using
      multiple logistic regression models. RESULTS: More that 20% of boys and 35% of
      girls perceived themselves to be too fat. Girls reported being on a diet more
      frequently than boys (28.8% vs. 14.9%). The most frequent weight-reduction
      behaviours were drinking more water (67.7%), eating more fruits and vegetables
      (67.1%), and consuming fewer sweets (60.5%) and soft drinks (51.7%). Girls
      prevailed above boys in the use of these dietary methods. Age differences were
      not apparent, except for smoking, believed to help in weight reduction and used
      upmost by 15-year-olds (8.9%) followed by 14 and 13-year-olds, 6.0% and 4.1%,
      respectively. CONCLUSIONS: Body-image dissatisfaction and weight-control
      behaviour are issues particularly in girls, however, they did not necessarily
      correspond with actual obesity. The most commonly used weight-reduction
      behaviours are in the same way important aspects of a healthy lifestyle. There is
      room to improve obesity control, particularly within primary health care.

PMID- 29022682
TI  - Self-reported Health Status Predicting Resilience and Burnout in Longitudinal
      Study.
AB  - OBJECTIVE: The study examined the links between health-related indicators, adult
      resilience, and burnout. METHOD: The data were collected during two waves of the
      longitudinal study (in 2004-05, N=98, and 2011-12, N=88, respectively). Health
      behaviour, self-rated health (SRH), Sense of Coherence Scale (SOC), and Shirom
      Melamed Burnout Measure (SMBM) were measured. RESULTS: The comprehensibility of
      SOC and physical fatigue of SMBM as measured in wave 2 were determined by SRH as
      measured in wave 1. In the cross-sectional part, the meaningfulness of SOC was
      related to SRH, and alcohol consumption in wave 1. The comprehensibility of SOC
      was related to SRH in wave 2. CONCLUSION: SOC is well known to have effect on
      health. However, the results show that self-reported health had effect on the
      comprehensibility of SOC. Our data also support the finding that the effect of
      SRH on burnout is stronger than the effect of burnout on SRH.

PMID- 29022684
TI  - Legionellosis: a Walk-through to Identification of the Source of Infection.
AB  - OBJECTIVES: Although a number of human Legionnaires' disease in tourists are
      recorded annually in Europe, there are few cases where a direct link can be made
      between the infected person and the source of infection (hotel or other
      accommodation). We present a scheme followed in order to track down and identify
      the source of infection in a tourist suffering from L. pneumophila sg 5
      infection, who was accommodated in seven different hotels during his holidays in
      the island of Crete, and we comment on various difficulties and draw-backs of the
      process. METHOD: Water samples were collected from the seven hotels where the
      patient had resided and analyzed at the regional public health laboratory using
      cultivation and molecular tests. RESULTS: Of 103 water samples analyzed, 19
      (18.4%) were positive for Legionella non-pneumophila and 8 (7.8%) were positive
      for L. pneumophila. A successful L. pneumophila sg 5 match was found between the
      clinical and environmental sample, which led us to the final identification of
      the liable hotel. CONCLUSION: Timely notification of the case, within the the
      European Legionnaires' Disease Surveillance Network (ELDSNet) of the partners
      involved, is crucial during a course of travel associated with Legionella case
      investigation. Moreover, the urinary antigen test alone cannot provide sufficient
      information for the source identification. However, acquiring clinical as well as
      environmental isolates for serogroup and SBT identification is highly important
      for the successful matching.

PMID- 29022683
TI  - National Laboratory Surveillance of Influenza in Macedonia during Four Seasons.
AB  - OBJECTIVE: The aim of the study is to comprehend results of the influenza lab
      surveillance system in the Republic of Macedonia after the 2009 pandemic and to
      determine the main characteristics of four consecutive epidemic seasons (from
      2010/2011 until 2013/2014). METHODS: As part of the universal surveillance
      system, nasal and throat specimens were collected from patients. After extraction
      of RNA, the CDC real-time RT-PCR assays for the detection of influenza types and
      subtypes were performed. RESULTS: Out of 920 tested samples, 406 (44.1%)
      laboratory confirmed cases of influenza were found. Influenza activity begins as
      early as December and continues until the end of April with peaks in January or
      February with predominant influenza A and A/H1N1pdm. Influenza A viruses start
      their activity at week 49 to 52 and subside at week 17. Usually two peaks appear,
      the first one between week 2 and 4 and the second one between week 6 and 9.
      Subtype A/H1N1pdm was dominant among influenza A types in the 2010/2011 and
      2012/2013 seasons. A/H3N2 was the only circulating influenza virus in the
      2011/2012 season. Influenza B season is shorter and has only one peak, between
      weeks 2-5. Usually the influenza B viruses emerge in later stages than influenza
      A viruses, except for the first post-pandemic season. CONCLUSION: Results
      revealed that post-pandemic influenza seasons in Macedonia were rather different.
      Although the influenza season pattern is similar to patterns in some countries of
      the WHO European region, some unique characteristics were observed.

PMID- 29022685
TI  - Inverse Relationship between Adherence to the Mediterranean Diet and Serum
      Cystatin C Levels.
AB  - OBJECTIVE: The aim of the present study was to examine serum cystatin C levels in
      association with the Mediterranean diet in a healthy Greek population. METHODS:
      Cystatin C together with basic clinical chemistry tests was measured in a total
      of 490 adults (46+/-16 years, 40% of males), who underwent an annual health
      check. Demographic, anthropometric and lifestyle characteristics were recorded,
      while adherence to the Mediterranean diet was evaluated through the MedDietScore
      (0-55). RESULTS: The mean level of serum cystatin C was 0.84 mg/L, while men had
      increased serum cystatin C levels compared to women (0.86 mg/L vs. 0.83 mg/L,
      respectively, 0.017). After adjusting for age, gender, body mass index, smoking
      status, hypertension, diabetes, hypercholesterolemia, estimated glomerular
      filtration rate (eGFR), albumin and ferritin levels, each unit increase in
      MedDietScore led to 0.002 mg/dL drop off in cystatin C serum levels. CONCLUSIONS:
      We have demonstrated an inverse relationship between the MedDietScore and serum
      cystatin C levels. Our finding that increases in MedDietScore are associated with
      decreases in serum cystatin C levels could imply that adherence to the
      Mediterranean diet may reduce the cardiovascular risk, as assessed by cystatin C,
      a prognostic marker of the cardiometabolic risk. This notion could have a great
      impact on public health.

PMID- 29022686
TI  - Level of Education as a Risk Factor for Extensive Prevalence of Cervical
      Intervertebral Disc Degenerative Changes and Chronic Neck Pain.
AB  - OBJECTIVE: The aim of this study was to document the prevalence of degenerative
      intervertebral disc changes in the patients who previously reported symptoms of
      neck pain and to determine the influence of education level on degenerative
      intervertebral disc changes and subsequent chronic neck pain. METHODS: One
      hundred and twelve patients were randomly selected from the University Hospital
      in Mostar, Bosna and Herzegovina, (aged 48.5+/-12.7 years) and submitted to
      magnetic resonance imaging (MRI) of the cervical spine. MRI of 3.0 T (Siemens,
      Skyrim, Erlangen, Germany) was used to obtain cervical spine images. Patients
      were separated into two groups based on their education level: low education
      level (LLE) and high education level (HLE). Pfirrmann classification was used to
      document intervertebral disc degeneration, while self-reported chronic neck pain
      was evaluated using the previously validated Oswestry questionnaire. RESULTS: The
      entire logistic regression model containing all predictors was statistically
      significant, (chi2(3)=12.2, p=0.02), and was able to distinguish between
      respondents who had chronic neck pain and vice versa. The model explained between
      10.0% (Cox-Snell R2) and 13.8% (Nagelkerke R2) of common variance with Pfirrmann
      classification, and it had the strength to discriminate and correctly classify
      69.6% of patients. The probability of a patient being classified in the high or
      low group of degenerative disc changes according to the Pfirrmann scale was
      associated with the education level (Wald test: 5.5, p=0.02). Based on the
      Pfirrmann assessment scale, the HLE group was significantly different from the
      LLE group in the degree of degenerative changes of the cervical intervertebral
      discs (U=1,077.5, p=0.001). CONCLUSION: A moderate level of intervertebral disc
      degenerative changes (grade II and III) was equally matched among all patients,
      while the overall results suggest a higher level of education as a risk factor
      leading to cervical disc degenerative changes, regardless of age differences
      among respondents.

PMID- 29022687
TI  - Bohumir Prochazka, longtime CEJPH Editorial Board member, dies at 64.

PMID- 29022688
TI  - Hospital Quality and Hospital Value-Based Purchasing.

PMID- 29022689
TI  - Geriatric assessments and medication management in elderly oncology patients.

PMID- 29022690
TI  - Metallic versus Semiconducting SWCNT Chemiresistors: A Case for Separated SWCNTs
      Wrapped by a Metallosupramolecular Polymer.
AB  - As-synthesized single-walled carbon nanotubes (SWCNTs) are a mixture of metallic
      and semiconducting tubes, and separation is essential to improve the performances
      of SWCNT-based electric devices. Our chemical sensor monitors the conductivity of
      an SWCNT network, wherein each tube is wrapped by an insulating
      metallosupramolecular polymer (MSP). Vapors of strong electrophiles such as
      diethyl chlorophosphate (DECP), a nerve agent simulant, can trigger the
      disassembly of MSPs, resulting in conductive SWCNT pathways. Herein, we report
      that separated SWCNTs have a large impact on the sensitivity and selectivity of
      chemical sensors. Semiconducting SWCNT (S-SWCNT) sensors are the most sensitive
      to DECP (up to 10000% increase in conductivity). By contrast, the responses of
      metallic SWCNT (M-SWCNT) sensors were smaller but less susceptible to interfering
      signals. For saturated water vapor, increasing and decreasing conductivities were
      observed for S- and M-SWCNT sensors, respectively. Mixtures of M- and S-SWCNTs
      revealed reduced responses to saturated water vapor as a result of canceling
      effects. Our results reveal that S- and M-SWCNTs compensate sensitivity and
      selectivity, and the combined use of separated SWCNTs, either in arrays or in
      single sensors, offers advantages in sensing systems.

PMID- 29022691
TI  - Monolithic Two-Dimensional Photonic Crystal Reflectors for the Fabrication of
      Highly Efficient and Highly Transparent Dye-Sensitized Solar Cells.
AB  - The transparent characteristic of dye-sensitized solar cells (DSCs) makes them
      suitable for building integrated photovoltaic (BIPV) devices. However, the
      diffusive scattering layer, which is usually used to increase the efficiency of
      these devices, greatly lowers the transparency of the DSC. This paper described a
      two-dimensional (2D) photonic crystal (PC) reflector with a sub-micrometer
      characteristic length that can improve the efficiency of these devices while
      maintaining transparency. This 2D PCs were fabricated directly onto TiO2
      photoelectrodes using colloidal lithography and have the structure of a
      nanopillar array. A nanopillar with a height of 430 nm was observed to
      selectively reflect up to 40% of the light of 400-500 nm wavelength. The
      perceived transparency of the 2D PC electrode was 52%, which is much higher than
      0.3% of the conventional scattering layer. The DSC fabricated using the 2D PC
      electrode demonstrated a maximum photon-to-electric conversion efficiency of
      8.23%, which is 18% higher than the pristine electrode. The 2D PC is a highly
      efficient and wavelength-selective reflector that can be applied to various
      photoelectric conversion devices.

PMID- 29022692
TI  - Paper Spray Ionization Coupled to High Resolution Tandem Mass Spectrometry for
      Comprehensive Urine Drug Testing in Comparison to Liquid Chromatography-Coupled
      Techniques after Urine Precipitation or Dried Urine Spot Workup.
AB  - Screening procedures using high resolution (HR)-mass spectrometry (MS) are
      getting more and more important, e.g., for drug testing or adherence monitoring.
      Approaches usually include time-consuming sample preparation and compound
      separation by liquid chromatography (LC). The paper spray ionization (PSI)
      technique coupled to MS might overcome these steps by direct analysis of complex
      mixtures without extraction and separation. In recent years, this technology
      proved its potential for quantification and/or qualitative screening in
      biofluids. However, so far, PSI-MS was only applied to procedures covering a
      limited number of targets. Therefore, a PSI-HR-MS/MS approach was developed and
      successfully validated for comprehensive urine screening. The procedure showed
      high matrix effects for most drugs but still acceptable limits of identification.
      Applicability was tested by analyses of three proficiency tests for systematic
      toxicological analysis and of 103 authentic human urine samples. Its screening
      power was compared to that of published LC-HR-MS/MS procedures after urine
      precipitation with conjugate cleavage (UglucP) or dried urine spot workup by
      conjugate cleavage and liquid extraction (DUSglucE). In the authentic samples,
      73% of all 777 drug intakes were detectable with the new approach. The LC-HR
      MS/MS screening approaches detected more drugs, particularly in samples with low
      analyte concentrations, with values of 88% after UglucP or 76% after DUSglucE. In
      conclusion, the new PSI-HR-MS/MS screening approach was suitable for
      comprehensive urine screening of different drug classes and might be a promising
      alternative to conventional procedures. However, limitations should be considered
      such as detection of drugs in low concentrations and risk of false positive or
      negative results caused by mixed spectra.

PMID- 29022693
TI  - Trilayer Three-Dimensional Hydrogel Composite Scaffold Containing Encapsulated
      Adipose-Derived Stem Cells Promotes Bladder Reconstruction via SDF-1alpha/CXCR4
      Pathway.
AB  - Bladder acellular matrix graft-alginate dialdehyde-gelatin hydrogel-silk mesh
      (BAMG-HS) encapsulated with adipose-derived stem cells (ASCs) was evaluated in a
      rat model of augmentation cystoplasty, including BAMG-HS-ASCs (n = 18, subgroup n
      = 6 for 2, 4, and 12 weeks), acellular BAMG-HS (n = 6 for 12 weeks) and cystotomy
      control (n = 6 for 12 weeks) groups. Equipped with good cytocompatibility and
      superior mechanical properties (elastic modulus: 5.33 +/- 0.96 MPa, maximum load:
      28.90 +/- 0.69 N), BAMG-HS acted a trilayer "sandwich" scaffold with minimal
      interference in systemic homeostasis. ASCs in BAMG-HS promoted morphological and
      histological bladder restoration by accelerating scaffold degradation (p < 0.05),
      ameliorating fibrosis (p < 0.05) and inflammation (p < 0.01). Additionally, ASCs
      facilitated the recovery of bladder function by enhancing smooth muscle
      regeneration (p < 0.05), innervation (p < 0.01) and angiogenesis (p < 0.001).
      Except for a small number of endothelium-differentiated ASCs, the pro-angiogenic
      effects of ASCs were mainly related to ERK1/2 phosphorylation in the downstream
      of SDF-1alpha/CXCR4 pathway.

PMID- 29022694
TI  - Enhancing Distorted Metal-Organic Framework-Derived ZnO as Anode Material for
      Lithium Storage by the Addition of Ag2S Quantum Dots.
AB  - The lithium storage properties of the distorted metal-organic framework-derived
      nanosized ZnO@C are significantly improved by the introduction of Ag2S quantum
      dots (QDs) during the processing of the material. In the thermal treatment, the
      Ag2S QDs react to produce Ag nanoparticles and ZnS. The metal nanoparticles act
      to shorten electron pathways and improve the connectivity of the matrix, and the
      partial sulfidation of the ZnO surface improves the cycling stability of the
      material. The electrochemical properties of ZnO@C, Ag2S QDs-treated ZnO@C, and
      the amorphous carbon in ZnO@C have been compared. The small weight ratio of Ag2S
      QDs to ZnO@C at 1:180 shows the best performance in lithium storage. The
      exhibited specific capacities are improved and retained remarkably in the cycling
      at high current rates. At low current densities (200 mA g-1), treatment of ZnO@C
      with Ag2S QDs results in a 38% increase in the specific capacity.

PMID- 29022695
TI  - High Activity and Convenient Ratio Control: DNA-Directed Coimmobilization of
      Multiple Enzymes on Multifunctionalized Magnetic Nanoparticles.
AB  - The development of new methods for fabricating artificial multienzyme systems has
      attracted much interest because of the potential applications and the urgent need
      for multienzyme catalysts. Controlling the enzyme ratio is critical for improving
      the cooperative enzymatic activity in multienzyme systems. Herein, we introduce a
      versatile strategy for fabricating a multienzyme system by coimmobilizing
      horseradish peroxidase (HRP) and glucose oxidase (GOx) on magnetic nanoparticles
      multifunctionalized with dopamine derivatives through DNA-directed
      immobilization. This multienzyme system exhibited precise enzyme ratio control,
      high catalytic efficiency, magnetic retrievability, and enhanced stability. The
      enzyme ratio was conveniently adjusted, as required, by regulating the quantity
      of functional groups on the multifunctionalized nanoparticles. The optimal mole
      ratio of GOx/HRP was 2:1. The Michaelis constant Km and specificity constant
      (kcat/Km, where kcat is the catalytic rate constant) of the multienzyme system
      were 1.41 mM and 5.02 s-1 mM-1, respectively, which were approximately twice the
      corresponding values of free GOx&HRP. The increased bioactivity of the
      multienzyme system was ascribed to the colocalization of the involved enzymes and
      the promotion of DNA-directed immobilization. Given the wide variety of possible
      enzyme associations and the high efficiency of this strategy, we believe that
      this work provides a new route for the fabrication of artificial multienzyme
      systems and can be extended for a wide range of applications in diagnosis,
      biomedical devices, and biotechnology.

PMID- 29022696
TI  - Building Additional Passageways in Polyamide Membranes with Hydrostable Metal
      Organic Frameworks To Recycle and Remove Organic Solutes from Various Solvents.
AB  - Membrane separation is a promising technology for extracting temperature
      sensitive organic molecules from solvents. However, a lack of membrane materials
      that are permeable toward organic solvents yet highly selective curtails large
      scale membrane applications. To overcome the trade-off between flux and
      selectivity, additional molecular transportation pathways are constructed in
      ultrathin polyamide membranes using highly hydrostable metal organic frameworks
      with diverse functional surface architectures. Additional passageways enhance
      water permeance by 84% (15.4 L m-2 h-1 bar-1) with nearly 100% rose bengal
      rejection and 97.6% azithromycin rejection, while showing excellent separation
      performance in ethyl acetate, ketones, and alcohols. These unique composite
      membranes remain stable in both aqueous and organic solvent environments. This
      immediately finds application in the purification of aqueous mixtures containing
      organic soluble compounds, such as antibiotics, during pharmaceutical
      manufacturing.

PMID- 29022698
TI  - PCR-Free Colorimetric DNA Hybridization Detection Using a 3D DNA Nanostructured
      Reporter Probe.
AB  - A "sandwich-like" biosensor was developed on the basis of the magnetic bead
      platform for sensitive detection of breast cancer 1 (BRCA1) DNA. In the present
      study, a tetrahedron-structured reporter probe (TSRP) was designed, in which 3
      vertices of the tetrahedron were labeled with digoxin (Dig), and the other one
      was labeled with a detection probe. TSRP here provided accurate enzyme loading
      and well-organized spatial arrangement for optimized signal amplification. The
      detection limit of this biosensor was as low as 10 fM, which is at least 4 orders
      of magnitude lower than that of the single DNA probe (100 pM), and the signal
      gain was 2 times higher than the analysis using three one-dimensional (1D)
      reporter probes. We could distinguish DNA sequences with only 1 base mismatch,
      and the performance of our TSRP biosensor was proven to be equally good in both
      PCR products and real fetal calf serum (FCS) sample as in buffer. We believe this
      work provided a novel avenue for the development of signal amplification
      strategies.

PMID- 29022699
TI  - Scalable High-Affinity Stabilization of Magnetic Iron Oxide Nanostructures by a
      Biocompatible Antifouling Homopolymer.
AB  - Iron oxide nanostructures have been widely developed for biomedical applications
      because of their magnetic properties and biocompatibility. In clinical
      applications, stabilization of these nanostructures against aggregation and
      nonspecific interactions is typically achieved using weakly anchored
      polysaccharides, with better-defined and more strongly anchored synthetic
      polymers not commercially adopted because of their complexity of synthesis and
      use. Here, we show for the first time stabilization and biocompatibilization of
      iron oxide nanoparticles by a synthetic homopolymer with strong surface anchoring
      and a history of clinical use in other applications, poly(2-methacryloyloxyethyl
      phosphorylcholine) [poly(MPC)]. For the commercially important case of spherical
      particles, binding of poly(MPC) to iron oxide surfaces and highly effective
      individualization of magnetite nanoparticles (20 nm) are demonstrated. Next
      generation high-aspect-ratio nanowires (both magnetite/maghemite and core-shell
      iron/iron oxide) are, furthermore, stabilized by poly(MPC) coating, with the
      nanowire cytotoxicity at large concentrations significantly reduced. The
      synthesis approach exploited to incorporate functionality into the poly(MPC)
      chain is demonstrated by random copolymerization with an alkyne-containing
      monomer for click chemistry. Taking these results together, poly(MPC)
      homopolymers and random copolymers offer a significant improvement over current
      iron oxide nanoformulations, combining straightforward synthesis, strong surface
      anchoring, and well-defined molecular weight.

PMID- 29022700
TI  - Design and Selection of a Synthetic Feedback Loop for Optimizing Biofuel
      Tolerance.
AB  - Feedback control allows cells to dynamically sense and respond to environmental
      changes. However, synthetic controller designs can be challenging because of
      implementation issues, such as determining optimal expression levels for circuit
      components within a feedback loop. Here, we addressed this by coupling rational
      design with selection to engineer a synthetic feedback circuit to optimize
      tolerance of Escherichia coli to the biojet fuel pinene. E. coli can be
      engineered to produce pinene, but it is toxic to cells. Efflux pumps, such as the
      AcrAB-TolC pump, can improve tolerance, but pump expression impacts growth. To
      address this, we used feedback to dynamically regulate pump expression in
      response to stress. We developed a library with thousands of synthetic circuit
      variants and subjected it to three types of pinene treatment (none, constant, and
      varying pinene). We were able to select for strains that were biofuel tolerant
      without a significant growth cost in the absence of biofuel. Using next
      generation sequencing, we found common characteristics in the designs and
      identified controllers that dramatically improved biofuel tolerance.

PMID- 29022701
TI  - Genetic and Pharmacological Discovery for Alzheimer's Disease Using
      Caenorhabditis elegans.
AB  - The societal burden presented by Alzheimer's disease warrants both innovative and
      expedient means by which its underlying molecular causes can be both identified
      and mechanistically exploited to discern novel therapeutic targets and
      strategies. The conserved characteristics, defined neuroanatomy, and advanced
      technological application of Caenorhabditis elegans render this metazoan an
      unmatched tool for probing neurotoxic factors. In addition, its short lifespan
      and importance in the field of aging make it an ideal organism for modeling age
      related neurodegenerative disease. As such, this nematode system has demonstrated
      its value in predicting functional modifiers of human neurodegenerative
      disorders. Here, we review how C. elegans has been utilized to model Alzheimer's
      disease. Specifically, we present how the causative neurotoxic peptides, amyloid
      beta and tau, contribute to disease-like neurodegeneration in C. elegans and how
      they translate to human disease. Furthermore, we describe how a variety of
      transgenic animal strains, each with distinct utility, have been used to identify
      both genetic and pharmacological modifiers of toxicity in C. elegans. As
      technological advances improve the prospects for intervention, the rapidity,
      unparalleled accuracy, and scale that C. elegans offers researchers for defining
      functional modifiers of neurodegeneration should speed the discovery of improved
      therapies for Alzheimer's disease.

PMID- 29022697
TI  - Improved Photoinduced Fluorogenic Alkene-Tetrazole Reaction for Protein Labeling.
AB  - The 1,3-dipolar cycloaddition reaction between an alkene and a tetrazole
      represents one elegant and rare example of fluorophore-forming bioorthogonal
      chemistry. This is an attractive reaction for imaging applications in live cells
      that requires less intensive washing steps and/or needs spatiotemporal
      resolutions. In the present work, as an effort to improve the fluorogenic
      property of the alkene-tetrazole reaction, an aromatic alkene (styrene) was
      investigated as the dipolarophile. Over 30-fold improvement in quantum yield of
      the reaction product was achieved in aqueous solution. According to our
      mechanistic studies, the observed improvement is likely due to an insufficient
      protonation of the styrene-tetrazole reaction product. This finding provides
      useful guidance to the future design of alkene-tetrazole reactions for biological
      studies. Fluorogenic protein labeling using the styrene-tetrazole reaction was
      demonstrated both in vitro and in vivo. This was realized by the genetic
      incorporation of an unnatural amino acid containing the styrene moiety. It is
      anticipated that the combination of styrene with different tetrazole derivatives
      can generally improve and broaden the application of alkene-tetrazole chemistry
      in real-time imaging in live cells.

PMID- 29022702
TI  - Development of Bright and Biocompatible Nanoruby and Its Application to
      Background-Free Time-Gated Imaging of G-Protein-Coupled Receptors.
AB  - At the forefront of developing fluorescent probes for biological imaging
      applications are enhancements aimed at increasing their brightness, contrast, and
      photostability, especially toward demanding applications of single-molecule
      detection. In comparison with existing probes, nanorubies exhibit unlimited
      photostability and a long emission lifetime (~4 ms), which enable continuous
      imaging at single-particle sensitivity in highly scattering and fluorescent
      biological specimens. However, their wide application as fluorescence probes has
      so far been hindered by the absence of facile methods for scaled-up high-volume
      production and molecularly specific targeting. The present work encompasses the
      large-scale production of colloidally stable nanoruby particles, the
      demonstration of their biofunctionality and negligible cytotoxicity, as well as
      the validation of its use for targeted biomolecular imaging. In addition, optical
      characteristics of nanorubies are found to be comparable or superior to those of
      state-of-the-art quantum dots. Protocols of reproducible and robust coupling of
      functional proteins to the nanoruby surface are also presented. As an example,
      NeutrAvidin-coupled nanoruby show excellent affinity and specificity to MU-opioid
      receptors in fixed and live cells, allowing wide-field imaging of G-protein
      coupled receptors with single-particle sensitivity.

PMID- 29022703
TI  - Probing the Eumelanin-Silica Interface in Chemically Engineered Bulk Hybrid
      Nanoparticles for Targeted Subcellular Antioxidant Protection.
AB  - We disclose herein the first example of stable monodispersed hybrid nanoparticles
      (termed MelaSil-NPs) made up of eumelanin biopolymer intimately integrated into a
      silica nanoscaffold matrix and endowed with high antioxidant and cytoprotective
      effects associated with a specific subcellular localization. MelaSil-NPs have
      been fabricated by an optimized sol-gel methodology involving ammonia-induced
      oxidative polymerization of a covalent conjugate of the eumelanin building block
      5,6-dihydroxyindole-2-carboxylic acid (DHICA) with 3-aminopropyltriethoxysilanes
      (APTS). They displayed a round-shaped (ca. 50-80 nm) morphology, exhibited the
      typical electron paramagnetic resonance signal of eumelanin biopolymers, and
      proved effective in promoting decomposition of hydrogen peroxide under
      physiologically relevant conditions. When administered to human ovarian cancer
      cells (A2780) or cervical cancer cells (HeLa), MelaSil-NPs were rapidly
      internalized and colocalized with lysosomes and exerted efficient protecting
      effects against hydrogen peroxide-induced oxidative stress and cytotoxicity.

PMID- 29022704
TI  - A Kinetic Model of Nonenzymatic RNA Polymerization by Cytidine-5'-phosphoro-2
      aminoimidazolide.
AB  - The nonenzymatic polymerization of RNA may have enabled copying of functional
      sequences during the origin of life. Recent progress utilizing 5'-phosphoro-2
      aminoimidazole activation has reinvigorated the possibility of using nonenzymatic
      RNA polymerization for copying arbitrary sequences. However, the reasons why 2
      aminoimidazole (AI) is a superior activation group remain unclear. Here we report
      that the predominant mechanism of polymerization using cytidine-5'-phosphoro-2
      aminoimidazolide (Cp*) involves a 2-aminoimidazolium-bridged dinucleotide (Cp*pC)
      intermediate. To explore the role of this intermediate, we first identify and
      quantify four reactions involving the synthesis and breakdown of Cp*pC that occur
      in the absence of the primer-template duplex. We then analyze the dependence of
      the rate of polymerization on the concentration of the Cp*pC intermediate in the
      presence and absence of the competitive inhibitor Cp. We also show that the
      contribution of the monomer Cp* to the polymerization rate is negligible under
      our primer extension conditions. Finally, we use the experimentally determined
      rate constants of these reactions to develop a kinetic model that helps explain
      the changing rate of nonenzymatic RNA polymerization over time. Our model
      accounts for the concentration of Cp*pC formed by Cp* under primer extension
      conditions. The model does not completely account for the decline in
      polymerization rate observed over long times, which indicates that additional
      important inhibitory processes have not yet been identified. Our results suggest
      that the superiority of 2-aminoimidazole over the traditional 2-methylimidazole
      activation is mostly due to the higher level of accumulation of the imidazolium
      bridged intermediate under primer extension conditions.

PMID- 29022705
TI  - Platinum Complexes of N,N',N",N'''-Diboronazophenines.
AB  - Azophenine, (alpha-C6H5NH)2(C6H5-N?C6H2?N-C6H5), well known to be non-emissive,
      was rigidified by replacing two amine protons by two difluoroboranes (BF2+) and
      further functionalized at the para-positions of the phenyl groups by luminescent
      trans-ArC=C-Pt(PR3)2-C=C ([Pt]) arms [Ar = C6H4 (R = Et), hexa(n-hexyl)truxene)
      (Tru; R = Bu)]. Two effects are reported. First, the linking of these [Pt] arms
      with the central azophenine (C6H4-N?C6H2(NH)2?N-C6H4; Q) generates very low
      energy charge-transfer (CT) singlet and triplet excited states (3,1([Pt]-to-Q)*)
      with absorption bands extending all the way to 800 nm. Second, the rigidification
      of azophenine by the incorporation of BF2+ units renders the low-lying CT singlet
      state clearly emissive at 298 and 77 K in the near-IR region. DFT computations
      place the triplet emission in the 1200-1400 nm range, but no phosphorescence was
      detected. The photophysical properties are investigated, and circumstantial
      evidence for slow triplet energy transfers, 3Tru* -> Q, is provided.

PMID- 29022707
TI  - Bistable [c2] Daisy Chain Rotaxanes as Reversible Muscle-like Actuators in
      Mechanically Active Gels.
AB  - The implementation of molecular machines in polymer science is of high interest
      to transfer mechanical motions from nanoscale to macroscale in order to access
      new kinds of active devices and materials. Toward this objective, thermodynamic
      and topological aspects need to be explored for reaching efficient systems
      capable of producing a useful work. In this paper we describe the branched
      polymerization of pH-sensitive bistable [c2] daisy chain rotaxanes by using
      copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition ("click chemistry"). With
      this cross-linked topology, the corresponding materials in the form of chemical
      gels can be contracted and expanded over a large variation of volume (~50%) by
      changing the protonation state of the system. HR-MAS 1H NMR and neutron
      scattering experiments reveal that this macroscopic response of the gels results
      from the synchronized actuation of the mechanical bonds at the molecular level.

PMID- 29022706
TI  - Understanding and Interrupting the Fischer Azaindolization Reaction.
AB  - Experimental and computational studies pertaining to the Fischer azaindolization
      reaction are reported. These studies explain why pyridylhydrazines are poorly
      reactive in Fischer indolization reactions, in addition to the origin of
      hydrazine substituent effects. Additionally, an interrupted variant of Fischer
      azaindolization methodology is disclosed, which provides a synthetic entryway
      into fused azaindoline scaffolds.

PMID- 29022708
TI  - Dynamic Model for the Stocks and Release Flows of Engineered Nanomaterials.
AB  - Most existing life-cycle release models for engineered nanomaterials (ENM) are
      static, ignoring the dynamics of stock and flows of ENMs. Our model, nanoRelease,
      estimates the annual releases of ENMs from manufacturing, use, and disposal of a
      product explicitly taking stock and flow dynamics into account. Given the
      variabilities in key parameters (e.g., service life of products and annual
      release rate during use) nanoRelease is designed as a stochastic model. We apply
      nanoRelease to three ENMs (TiO2, SiO2 and FeOx) used in paints and coatings
      through seven product applications, including construction and building,
      household and furniture, and automotive for the period from 2000 to 2020 using
      production volume and market projection information. We also consider model
      uncertainties using Monte Carlo simulation. Compared with 2016, the total annual
      releases of ENMs in 2020 will increase by 34-40%, and the stock will increase by
      28-34%. The fraction of the end-of-life release among total release flows will
      increase from 11% in 2002 to 43% in 2020. As compared to static models, our
      dynamic model predicts about an order of magnitude lower values for the amount of
      ENM released from this sector in the near-term while stock continues to build up
      in the system.

PMID- 29022710
TI  - Probing Charge Carrier Dynamics in Porphyrin-Based Organic Semiconductor Thin
      Films by Time-Resolved THz Spectroscopy.
AB  - To improve the power conversion efficiency of solar cells, it is important to
      understand the underlying relaxation mechanisms of photogenerated charge carriers
      in organic semiconductors. In this work, we studied the charge carrier dynamics
      of diketopyrrolopyrrole-linked tetrabenzoporphyrin thin films where the
      diketopyrrolopyrrole unit has two n-butyl groups, abbreviated as C4-DPP-BP. We
      used time-resolved terahertz (THz) spectroscopy to track charge carrier dynamics
      with excitations at 800 and 400 nm. Compared with tetrabenzoporphyrin (BP), the
      extension of pi-electron delocalization to the diketopyrrolopyrrole peripherals
      leads to an increase in absorption in the near-infrared region. Following the
      excitation at 800 nm, we found that the transient THz signals in C4-DPP-BP thin
      films decay with time constants of 0.5 and 9.1 ps, with small residual
      components. With excitation at 400 nm, we found that the transient THz signals
      decay with time constants of 0.4 and 7.5 ps. On the basis of the similarity of
      the decay profiles of the transient THz signals obtained with excitations at 400
      and 800 nm, we considered that the decaying components are due to charge carrier
      recombination and/or trapping at defect sites, which do not depend on the excess
      energy of the photoexcitation. In contrast to BP, even without an electron
      acceptor, we observed the finite offset of the transient THz signals at 100 ps,
      demonstrating the existence of long-lived charge carriers. We also measured the
      photoconductivity spectra of C4-DPP-BP thin films with the excitation at both 800
      and 400 nm. It was found that the spectra can be fitted by the Drude-Smith model.
      From these results, it was determined that the charge carriers are localized
      right after photoexcitation. At 0.4 ps, the product of the quantum yield of
      charge generation and mobility of charge carriers at 400 nm is approximately
      twice that obtained at 800 nm. We discuss the implications of the excess
      excitation energy in organic semiconductor-based devices.

PMID- 29022709
TI  - Directed gamma-C(sp3)-H Alkylation of Carboxylic Acid Derivatives through Visible
      Light Photoredox Catalysis.
AB  - Visible light photoredox catalysis enables direct gamma- C(sp3)-H alkylation of
      saturated aliphatic carbonyl compounds. Electron-deficient alkenes are used as
      the coupling partners in this reaction. Distinguished site selectivity is
      controlled by the predominant 1,5-hydrogen atom transfer of an amidyl radical
      generated in situ.

PMID- 29022711
TI  - Selenoglutathione Diselenide: Unique Redox Reactions in the GPx-Like Catalytic
      Cycle and Repairing of Disulfide Bonds in Scrambled Protein.
AB  - Selenoglutathione (GSeH) is a selenium analogue of naturally abundant glutathione
      (GSH). In this study, this water-soluble small tripeptide was synthesized in a
      high yield (up to 98%) as an oxidized diselenide form, i.e., GSeSeG (1), by
      liquid-phase peptide synthesis (LPPS). Obtained 1 was applied to the
      investigation of the glutathione peroxidase (GPx)-like catalytic cycle. The
      important intermediates, i.e., GSe- and GSeSG, besides GSeO2H were characterized
      by 77Se NMR spectroscopy. Thiol exchange of GSeSG with various thiols, such as
      cysteine and dithiothreitol, was found to promote the conversion to GSe-
      significantly. In addition, disproportionation of GSeSR to 1 and RSSR, which
      would be initiated by heterolytic cleavage of the Se-S bond and catalyzed by the
      generated selenolate, was observed. On the basis of these redox behaviors, it was
      proposed that the heterolytic cleavage of the Se-S bond can be facilitated by the
      interaction between the Se atom and an amino or aromatic group, which is present
      at the GPx active site. On the other hand, when a catalytic amount of 1 was
      reacted with scrambled 4S species of RNase A in the presence of NADPH and
      glutathione reductase, native protein was efficiently regenerated, suggesting a
      potential use of 1 to repair misfolded proteins through reduction of the non
      native SS bonds.

PMID- 29022712
TI  - Predictive Structure-Based Toxicology Approaches To Assess the Androgenic
      Potential of Chemicals.
AB  - We present a practical and easy-to-run in silico workflow exploiting a structure
      based strategy making use of docking simulations to derive highly predictive
      classification models of the androgenic potential of chemicals. Models were
      trained on a high-quality chemical collection comprising 1689 curated compounds
      made available within the CoMPARA consortium from the US Environmental Protection
      Agency and were integrated with a two-step applicability domain whose
      implementation had the effect of improving both the confidence in prediction and
      statistics by reducing the number of false negatives. Among the nine androgen
      receptor X-ray solved structures, the crystal 2PNU (entry code from the Protein
      Data Bank) was associated with the best performing structure-based classification
      model. Three validation sets comprising each 2590 compounds extracted by the DUD
      E collection were used to challenge model performance and the effectiveness of
      Applicability Domain implementation. Next, the 2PNU model was applied to screen
      and prioritize two collections of chemicals. The first is a small pool of 12
      representative androgenic compounds that were accurately classified based on
      outstanding rationale at the molecular level. The second is a large external
      blind set of 55450 chemicals with potential for human exposure. We show how the
      use of molecular docking provides highly interpretable models and can represent a
      real-life option as an alternative nontesting method for predictive toxicology.

PMID- 29022713
TI  - Extending the Nonbonded Cationic Dummy Model to Account for Ion-Induced Dipole
      Interactions.
AB  - Modeling metalloproteins often requires classical molecular dynamics (MD)
      simulations in order to capture their relevant motions, which in turn
      necessitates reliable descriptions of the metal centers involved. One of the most
      successful approaches to date is provided by the "cationic dummy model", where
      the positive charge of the metal ion is transferred toward dummy particles that
      are bonded to the central metal ion in a predefined coordination geometry. While
      this approach allows for ligand exchange, and captures the correct electrostatics
      as demonstrated for different divalent metal ions, current dummy models neglect
      ion-induced dipole interactions. In the present work, we resolve this weakness by
      taking advantage of the recently introduced 12-6-4 type Lennard-Jones potential
      to include ion-induced dipole interactions. We revise our previous dummy model
      for Mg2+ and demonstrate that the resulting model can simultaneously reproduce
      the experimental solvation free energy and metal-ligand distances without the
      need for artificial restraints or bonds. As ion-induced dipole interactions
      become particularly important for highly charged metal ions, we develop dummy
      models for the biologically relevant ions Al3+, Fe3+, and Cr3+. Finally, the
      effectiveness of our new models is demonstrated in MD simulations of several
      diverse (and highly challenging to simulate) metalloproteins.

PMID- 29022714
TI  - Understanding the Effects of a High Surface Area Nanostructured Indium Tin Oxide
      Electrode on Organic Solar Cell Performance.
AB  - Organic solar cells (OSCs) are a complex assembly of disparate materials, each
      with a precise function within the device. Typically, the electrodes are flat,
      and the device is fabricated through a layering approach of the interfacial
      layers and photoactive materials. This work explores the integration of high
      surface area transparent electrodes to investigate the possible role(s) a three
      dimensional electrode could take within an OSC, with a BHJ composed of a donor
      acceptor combination with a high degree of electron and hole mobility mismatch.
      Nanotree indium tin oxide (ITO) electrodes were prepared via glancing angle
      deposition, structures that were previously demonstrated to be single
      crystalline. A thin layer of zinc oxide was deposited on the ITO nanotrees via
      atomic layer deposition, followed by a self-assembled monolayer of C60-based
      molecules that was bound to the zinc oxide surface through a carboxylic acid
      group. Infiltration of these functionalized ITO nanotrees with the photoactive
      layer, the bulk heterojunction comprising PC71BM and a high hole mobility low
      band gap polymer (PDPPTT-T-TT), led to families of devices that were analyzed for
      the effect of nanotree height. When the height was varied from 0 to 50, 75, 100,
      and 120 nm, statistically significant differences in device performance were
      noted with the maximum device efficiencies observed with a nanotree height of 75
      nm. From analysis of these results, it was found that the intrinsic mobility
      mismatch between the donor and acceptor phases could be compensated for when the
      electron collection length was reduced relative to the hole collection length,
      resulting in more balanced charge extraction and reduced recombination, leading
      to improved efficiencies. However, as the ITO nanotrees increased in height and
      branching, the decrease in electron collection length was offset by an increase
      in hole collection length and potential deleterious electric field redistribution
      effects, resulting in decreased efficiency.

PMID- 29022715
TI  - High-Efficiency Optical Gain in Type-II Semiconductor Nanocrystals of Alloyed
      Colloidal Quantum Wells.
AB  - Colloidal nanocrystals having controlled size, tailored shape, and tuned
      composition have been explored for optical gain and lasing. Among these,
      nanocrystals having Type-II electronic structure have been introduced toward low
      threshold gain. However, to date, their performance has remained severely limited
      due to diminishing oscillator strength and modest absorption cross-section.
      Overcoming these problems, here we realize highly efficient optical gain in Type
      II nanocrystals by using alloyed colloidal quantum wells. With composition-tuned
      core/alloyed-crown CdSe/CdSexTe1-x quantum wells, we achieved amplified
      spontaneous emission thresholds as low as 26 MUJ/cm2, long optical gain lifetimes
      (taugain ~ 400 ps), and high modal gain coefficients (gmodal ~ 930 cm-1). We
      uncover that the optical gain in these Type-II quantum wells arises from the
      excitations localized to the alloyed-crown region that are electronically coupled
      to the charge-transfer state. These alloyed heteronanostructures exhibiting
      remarkable optical gain performance are expected to be highly appealing for
      future display and lighting technologies.

PMID- 29022718
TI  - Multilayer Growth of Porphyrin-Based Polyurea Thin Film Using Solution-Based
      Molecular Layer Deposition Technique.
AB  - Controllable synthesis of organic thin film materials on solid surfaces is a
      challenging issue in the research field of surface science, as it is affected by
      several physical parameters. In this work, we demonstrated a solution-based
      molecular layer deposition (MLD) approach to prepare porphyrin-based covalent
      organic molecular networks on a 3-aminopropyl trimethoxysilane (APTMS) modified
      substrate surface using the urea coupling reaction between 1,4-phenylene
      diisocyanate (1,4-PDI) and 5,10,15,20-tetrakis-(4-aminophenyl) porphyrin (H2TAPP)
      at room temperature (22 +/- 2  degrees C). Multilayer growth was investigated
      under different relative humidity (RH) conditions of the reaction chamber.
      Sequential molecular growth at low relative humidity (<=10% RH) was observed
      using UV-vis absorption spectroscopy and atomic force microscopy (AFM). The high
      RH condition shows limited film growth. Infrared spectroscopy (IR) and X-ray
      photoelectron spectroscopy (XPS) revealed the polyurea bond formation in
      sequential multilayer thin films, demonstrating that stepwise multilayer film
      growth was achieved using the urea coupling reaction.

PMID- 29022717
TI  - Complex Emulsions by Extracting Water from Homogeneous Solutions Comprised of
      Aqueous Three-Phase Systems.
AB  - Multiple emulsions can be obtained by binary and ternary liquid phase separation.
      And the use of the aqueous two-phase system provides a simple route to prepare
      water-in-water-in-oil (W/W/O) or water-in-water-in-water (W/W/W) multiple
      emulsions. It is thus expected that we can fabricate more complex emulsions by
      using an aqueous three-phase system. Herein, we present a simple and versatile
      method to generate complex emulsions based on phase separation in homogeneous
      droplets made up of aqueous three-phase system: poly(ethylene glycol) (PEG),
      poly(vinyl alcohol) (PVA) and dextran (DEX) through extracting water from
      droplets. We examine the formation process and the effect of mass ratio of each
      two components in the three phase system. Emulsion droplets with five types of
      morphologies, i.e., binary-core/shell, core/shell-single phase Janus, ellipsoid
      Janus, multicore-in-matrix and single core-double shell morphologies can be
      formed, depending on the mass ratio of each two components and modification of
      PEG with Fe3O4 nanoparticles. We observe transition of core/shell-single phase
      Janus to binary-core/shell and single core-double shell to core/shell-single
      phase Janus geometry with prolongation of extracting time, and obtain the
      geometry map for the formation of different shaped droplets. Due to different
      affinities of PEG, PVA and DEX to certain materials, we functionalize each
      compartment in the complex emulsion droplets, and apply the resulting droplet for
      glucose sensing and the construction of antibody-mediated targeting drug
      delivery. This emulsion generation method is simple and the choice for the
      component of the aqueous three-phase system is broad, which can be further
      extended to generate complex emulsions from aqueous multiphase systems.

PMID- 29022716
TI  - Bespoke Diblock Copolymer Nanoparticles Enable the Production of Relatively
      Stable Oil-in-Water Pickering Nanoemulsions.
AB  - Sterically stabilized diblock copolymer nanoparticles with an intensity-average
      diameter of 25 nm are prepared in the form of a concentrated aqueous dispersion
      using polymerization-induced self-assembly (PISA). The addition of n-dodecane
      followed by high-shear homogenization produces n-dodecane-in-water Pickering
      macroemulsions of 22-46 MUm diameter. If the nanoparticles are present in
      sufficient excess, then subsequent processing using a high-pressure
      microfluidizer leads to the formation of Pickering nanoemulsions with a mean oil
      droplet diameter below 200 nm. The size of these Pickering nanoemulsions can be
      tuned by systematically varying the nanoparticle concentration, applied pressure,
      number of passes, and oil volume fraction. High-internal-phase emulsions can also
      be achieved by increasing the n-dodecane volume fraction up to 0.80. TEM studies
      of (dried) n-dodecane droplets confirm the presence of intact nanoparticles and
      suggest a relatively high surface coverage, which is consistent with model
      packing calculations based on radius ratios. Such Pickering nanoemulsions proved
      to be surprisingly stable with respect to Ostwald ripening, with no significant
      change in the mean DLS droplet diameter after storage for approximately 4 months
      at 20  degrees C.

PMID- 29022719
TI  - The Protein Corona of PEGylated PGMA-Based Nanoparticles is Preferentially
      Enriched with Specific Serum Proteins of Varied Biological Function.
AB  - The composition of the protein corona formed on poly(ethylene glycol)
      functionalized (PEGylated) poly(glycidyl methacrylate) (PGMA) nanoparticles (NPs)
      was qualitatively and quantitatively compared to the protein corona on non
      PEGylated PGMA NPs. Despite the reputation of PEGylated NPs for stealth
      functionality, we demonstrate the preferential enrichment of specific serum
      proteins of varied biological function in the protein corona on PEGylated NPs
      when compared to non-PEGylated NPs. Additionally, we suggest that the base
      material of polymeric NPs plays a role in the preferential enrichment of select
      serum proteins to the hard corona.

PMID- 29022720
TI  - Photoredox-Catalyzed Cross-Coupling of Enamides for the Assembly of beta
      Difluoroimine Synthons.
AB  - A photoredox-catalyzed formal Csp3-Csp3 cross-coupling reaction of enamides with
      bromodifluoro compounds is established. The resulting gem-difluoromethylenated
      gamma-imines indicated high stability, excellent E/Z control, and broad
      functional group tolerance. These synthetic intermediates can efficiently
      transfer to difluoromethylenated gamma-amino acids or delta-amino alcohols.
      Mechanistic analysis indicates that a radical/SET mechanism proceeding via a
      difluoroalkyl radical may be involved in the catalytic cycle.

PMID- 29022721
TI  - Experimental Evaluation of the Density of Water in a Cell by Raman Microscopy.
AB  - We report direct observation of a spatial distribution of water molecules inside
      of a living cell using Raman images of the O-H stretching band of water. The O-H
      Raman intensity of the nucleus was higher than that of the cytoplasm, indicating
      that the water density is higher in the nucleus than that in the cytoplasm. The
      shape of the O-H stretching band of the nucleus differed from that of the
      cytoplasm but was similar to that of the balanced salt solution surrounding
      cells, indicating less crowded environments in the nucleus. The concentration of
      biomolecules having C-H bonds was also estimated to be lower in the nucleus than
      that in the cytoplasm. These results indicate that the nucleus is less crowded
      with biomolecules than the cytoplasm.

PMID- 29022723
TI  - Motivated reasoning during recruitment.
AB  - This research shows how job postings can lead job candidates to see themselves as
      particularly deserving of hiring and high salary. We propose that these
      entitlement beliefs entail both personal motivations to see oneself as deserving
      and the ability to justify those motivated judgments. Accordingly, we predict
      that people feel more deserving when qualifications for a job are vague and thus
      amenable to motivated reasoning, whereby people use information selectively to
      reach a desired conclusion. We tested this hypothesis with a 2-phase experiment
      (N = 892) using materials drawn from real online job postings. In the first phase
      of the experiment, participants believed themselves to be more deserving of
      hiring and deserving of higher pay after reading postings composed of vaguer
      types of qualifications. In the second phase, yoked observers believed that
      participants were less entitled overall, but did not selectively discount
      endorsement of vaguer qualifications, suggesting they were unaware of this
      effect. A follow-up preregistered experiment (N = 905) using postings with mixed
      qualification types replicated the effect of including more vague qualifications
      on participants' entitlement beliefs. Entitlement beliefs are widely seen as
      problematic for recruitment and retention, and these results suggest that
      reducing the inclusion of vague qualifications in job postings would dampen the
      emergence of these beliefs in applicants, albeit at the cost of decreasing
      application rates and lowering applicants' confidence. (PsycINFO Database Record

PMID- 29022722
TI  - The impact of negative affect on attention patterns to threat across the first 2
      years of life.
AB  - The current study examined the relations between individual differences in
      attention to emotion faces and temperamental negative affect across the first 2
      years of life. Infant studies have noted a normative pattern of preferential
      attention to salient cues, particularly angry faces. A parallel literature
      suggests that elevated attention bias to threat is associated with anxiety,
      particularly if coupled with temperamental risk. Examining the emerging relations
      between attention to threat and temperamental negative affect may help
      distinguish normative from at-risk patterns of attention. Infants (N = 145) ages
      4 to 24 months (M = 12.93 months, SD = 5.57) completed an eye-tracking task
      modeled on the attention bias "dot-probe" task used with older children and
      adults. With age, infants spent greater time attending to emotion faces,
      particularly threat faces. All infants displayed slower latencies to fixate to
      incongruent versus congruent probes. Neither relation was moderated by
      temperament. Trial-by-trial analyses found that dwell time to the face was
      associated with latency to orient to subsequent probes, moderated by the infant's
      age and temperament. In young infants low in negative affect longer processing of
      angry faces was associated with faster subsequent fixation to probes; young
      infants high in negative affect displayed the opposite pattern at trend. Findings
      suggest that although age was directly associated with an emerging bias to
      threat, the impact of processing threat on subsequent orienting was associated
      with age and temperament. Early patterns of attention may shape how children
      respond to their environments, potentially via attention's gate-keeping role in
      framing a child's social world for processing. (PsycINFO Database Record

PMID- 29022724
TI  - Age differences in positive feelings and their expression.
AB  - Although various studies point to the importance of positive emotions for health
      and well-being across the entire life span, current research on age differences
      in emotional reactivity mainly focuses on negative emotions. Empirical evidence
      on positive emotions is scarce and mixed. Part of the inconsistencies may be
      related to study differences in the stimuli used and the emotional response
      systems considered. Thus, the present study examined different response systems
      (i.e., subjective feelings, facial and verbal expressions) and used internal
      stimuli of high personal relevance to all participants. More specifically, we
      used a modified relived emotion task in which younger (M = 25.64, SD = 4.05) and
      older (M = 70.06, SD = 3.94) adults first privately relived emotions associated
      with a recent positive event in their life, and subsequently thought aloud about
      this event and its accompanying feelings. We additionally explored whether
      conscientiousness, as a marker of self-regulatory skills, is associated with
      interindividual and age-related differences in positive emotions. During the
      relived emotion task, there were no age differences in positive feelings;
      however, compared with young adults, older adults reported more positive feelings
      during the think-aloud phase. Contrary to our prediction, however, older adults
      verbally and nonverbally expressed fewer positive emotions than their younger
      counterparts. Moreover, conscientiousness was associated with individual and age
      related differences in positive feelings, pointing to the potential explanatory
      role of self-regulatory skills in the experience of positive emotions. (PsycINFO
      Database Record

PMID- 29022726
TI  - Common marmoset (Callithrix jacchus) personality.
AB  - Increasing evidence suggests that personality structure differs between species,
      but the evolutionary reasons for this variation are not fully understood. We
      built on earlier research on New World monkeys to further elucidate the evolution
      of personality structure in primates. We therefore examined personality in 100
      family-reared adult common marmosets (Callithrix jacchus) from 3 colonies on a 60
      item questionnaire. Principal components analyses revealed 5 domains that were
      largely similar to those found in a previous study on captive, ex-pet, or
      formerly laboratory-housed marmosets that were housed in a sanctuary. The
      interrater reliabilities of domain scores were consistent with the interrater
      reliabilities of domain scores found in other species, including humans. Four
      domainsdmdash;conscientiousness, agreeableness, inquisitiveness, and
      assertiveness-resembled personality domains identified in other nonhuman
      primates. The remaining domain, patience, was specific to common marmosets. We
      used linear models to test for sex and age differences in the personality
      domains. Males were lower than females in patience, and this difference was
      smaller in older marmosets. Older marmosets were lower in inquisitiveness.
      Finally, older males and younger females had higher scores in agreeableness than
      younger males and older females. These findings suggest that cooperative breeding
      may have promoted the evolution of social cognition and influenced the structure
      of marmoset prosocial personality characteristics. (PsycINFO Database Record

PMID- 29022727
TI  - The power of negative mood in predicting posttraumatic stress disorder and
      alcohol abuse comorbidity.
AB  - OBJECTIVE: Individuals with posttraumatic stress disorder (PTSD) show a high risk
      of developing substance use disorders (SUD). Many studies have shown that PTSD
      often precedes SUD, and some studies have been able to identify factors that
      might predict which individuals might develop subsequent SUD. Attempts to treat
      PTSD and SUD comorbidity have proven difficult, but new methods for simultaneous
      treatment have shown promise for treating PTSD. The ability to identify factors
      that predict PTSD/SUD comorbidity and the advent of new combined treatment
      methods warrant investigation of how differences in specific types of PTSD
      symptoms individuals experience might predict who will go on to develop SUD
      symptoms and thus benefit from new combined treatments. METHOD: In this study, we
      analyzed which clusters of PTSD symptoms predicted whether individuals with PTSD
      met criteria for alcohol use disorder. RESULTS: Analyses revealed that frequency
      and intensity of negative alterations in cognition and mood predicted SUD, but re
      experiencing symptoms, hyperarousal, and avoidance did not. CONCLUSIONS: Our
      results indicate that those who experience negative alterations in cognition and
      mood may be at increased risk of developing SUD, and that we may be able to
      predict which individuals in clinical settings will be strong candidates for new
      combined PTSD/SUD treatments. Further considerations for our results and for
      future directions are also discussed. (PsycINFO Database Record

PMID- 29022725
TI  - Reduced impact of alcohol use on next-day tiredness in older relative to younger
      adults: A role for sleep duration.
AB  - Recent work has suggested that older adults may be less susceptible to the next
      day effects of alcohol relative to younger adults. The effects of alcohol in
      younger adults may be mediated by sleep duration, but due to age differences in
      the contexts of alcohol use, this mediation process may not generalize to older
      adults. The present study examined age-group (younger vs. older adults)
      differences in how alcohol use influenced next-day tiredness during daily life.
      Reports of alcohol use, sleep duration, and next-day tiredness obtained on ~101
      days from 91 younger adults (ages 20-31 years) and 75 older adults (ages 65-80
      years) were modeled using a multilevel, moderated mediation framework. Findings
      indicated that (a) greater-than-usual alcohol use was associated with greater
      than-usual tiredness in younger adults only, (b) greater-than-usual alcohol use
      was associated with shorter-than-usual sleep duration in younger adults only, and
      (c) shorter-than-usual sleep duration was associated with greater tiredness in
      both younger and older adults. For the prototypical younger adult, a significant
      portion (43%) of the association between alcohol use and next-day tiredness could
      be explained assuming mediation through sleep duration, whereas there was no
      evidence of mediation for the prototypical older adult. Findings of age
      differences in the mediation process underlying associations among alcohol use,
      sleep, and tiredness provide insight into the mechanisms driving recent
      observations of reduced next-day effects of alcohol in older relative to younger
      adults. (PsycINFO Database Record

PMID- 29022729
TI  - The extent of skin bending rather than action possibilities explains why holes
      feel larger with the tongue than with the finger.
AB  - When small holes are felt with the tongue, they are perceived to be larger
      compared with when felt with the index finger. This oral illusion has not yet
      been consistently explained. From present action-specific accounts of perception,
      we derived a high-level sticking-action hypothesis to explain the oral illusion.
      In 5 experiments, we contrasted this hypothesis' predictions with predictions
      from the low-level bending hypothesis, which states that felt hole size decreases
      with decreasing bending of the skin at the hole's edges. Results from Experiments
      1 to 3 showed that felt hole size decreases with the pliability of the exploring
      effector (tongue > index finger > big toe, big fingers > small fingers), which
      affects skin bending, and that size perception with the highly pliable tongue is
      more accurate than with the less pliable finger and toe. Experiment 4 showed that
      holes of intermediate size are perceived to be larger with the tongue's tip than
      with its dorsum. Finally, exploration styles that lessen the skin's bending
      (using low vs. high tongue forces in Experiment 5) decreased perceived hole size.
      Overall, the results favor the low-level bending hypothesis over the high-level
      sticking-action hypothesis. (PsycINFO Database Record

PMID- 29022728
TI  - Stereo viewing modulates three-dimensional shape processing during object
      recognition: A high-density ERP study.
AB  - The role of stereo disparity in the recognition of 3-dimensional (3D) object
      shape remains an unresolved issue for theoretical models of the human visual
      system. We examined this issue using high-density (128 channel) recordings of
      event-related potentials (ERPs). A recognition memory task was used in which
      observers were trained to recognize a subset of complex, multipart, 3D novel
      objects under conditions of either (bi-) monocular or stereo viewing. In a
      subsequent test phase they discriminated previously trained targets from
      untrained distractor objects that shared either local parts, 3D spatial
      configuration, or neither dimension, across both previously seen and novel
      viewpoints. The behavioral data showed a stereo advantage for target recognition
      at untrained viewpoints. ERPs showed early differential amplitude modulations to
      shape similarity defined by local part structure and global 3D spatial
      configuration. This occurred initially during an N1 component around 145-190 ms
      poststimulus onset, and then subsequently during an N2/P3 component around 260
      385 ms poststimulus onset. For mono viewing, amplitude modulation during the N1
      was greatest between targets and distracters with different local parts for
      trained views only. For stereo viewing, amplitude modulation during the N2/P3 was
      greatest between targets and distracters with different global 3D spatial
      configurations and generalized across trained and untrained views. The results
      show that image classification is modulated by stereo information about the local
      part, and global 3D spatial configuration of object shape. The findings challenge
      current theoretical models that do not attribute functional significance to
      stereo input during the computation of 3D object shape. (PsycINFO Database Record

PMID- 29022730
TI  - Integration of serial sensory information in haptic perception of softness.
AB  - Redundant estimates of an environmental property derived simultaneously from
      different senses or cues are typically integrated according to the maximum
      likelihood estimation model (MLE): Sensory estimates are weighted according to
      their reliabilities, maximizing the percept's reliability. Mechanisms underlying
      the integration of sequentially derived estimates from one sense are less clear.
      Here we investigate the integration of serially sampled redundant information in
      softness perception. We developed a method to manipulate haptically perceived
      softness of silicone rubber stimuli during bare-finger exploration. We then
      manipulated softness estimates derived from single movement segments
      (indentations) in a multisegmented exploration to assess their contributions to
      the overall percept. Participants explored two stimuli in sequence, using 2-5
      indentations, and reported which stimulus felt softer. Estimates of the first
      stimulus's softness contributed to the judgments similarly, whereas for the
      second stimulus estimates from later compared to earlier indentations contributed
      less. In line with unequal weighting, the percept's reliability increased with
      increasing exploration length less than was predicted by the MLE model. This
      pattern of results is well explained by assuming that the representation of the
      first stimulus fades when the second stimulus is explored, which fits with a
      neurophysiological model of perceptual decisions (Deco, Rolls, & Romo, 2010).
      (PsycINFO Database Record

PMID- 29022731
TI  - Meta-analyses of cardiovascular reactivity to rumination: A possible mechanism
      linking depression and hostility to cardiovascular disease.
AB  - Rumination is a way of cognitive coping associated with depression and hostility
      that prolongs cardiovascular responses to stress. If repeated over time, the
      associated autonomic dysregulation may be 1 mechanism linking depression and
      hostility to cardiovascular disease. The current meta-analyses investigate the
      magnitude of cardiovascular responses (heart rate, diastolic blood pressure, and
      systolic blood pressure) to induced state sadness and angry rumination which are
      associated with depression and hostility, respectively. A literature search
      identified 43 studies (3,348 participants) meeting inclusion criteria. A random
      effects model was applied to calculate cardiovascular reactivity weighted effect
      sizes during induced sadness and angry rumination. Large and significant effect
      sizes were found for all analyses, with the standardized mean statistic, d, for
      single group designs ranging from .75 to 1.39. Results suggest that angry
      rumination may have larger cardiovascular effects than sadness rumination, and
      that rumination likely affects blood pressure more than heart rate. Potential
      implications of this relationship are discussed in light of limitations of the
      current study and existing rumination research. (PsycINFO Database Record

PMID- 29022732
TI  - PDTRT special section: Methodological issues in personality disorder research.
AB  - Personality Disorders: Theory, Research, and Treatment includes a rolling,
      ongoing Special Section concerned with methodological issues in personality
      disorder research. This third edition of this series includes two articles. The
      first is by Brian Hicks, Angus Clark, and Emily Durbin: "Person-Centered
      Approaches in the Study of Personality Disorders." The second article is by Steve
      Balsis: "Item Response Theory Applications in Personality Disorder Research."
      Both articles should be excellent resources for future research and certainly
      manuscripts submitted to this journal that use these analytic tools. (PsycINFO
      Database Record

PMID- 29022734
TI  - Item response theory applications in personality disorder research.
AB  - This article describes how item response theory (IRT) has begun to address
      several of the measurement limitations inherent in the personality disorder (PD)
      literature. In particular, we describe how IRT can be used to improve PD
      measurement precision, develop PD instruments, and inform PD theory. In closing,
      we address a key assumption of unidimensional IRT models, and address the need to
      move beyond these models to include multidimensional models. In this context, we
      outline what we see as a future direction in PD measurement. (PsycINFO Database
      Record

PMID- 29022735
TI  - The Culture and Protective Suicide Scale for Incarcerated Persons (CAPSSIP): A
      measure for evaluating suicide risk and protection within correctional
      populations.
AB  - Suicide risk and protective factors function for prisoners within the context of
      incarceration. The Culture and Protective Suicide Scale for Incarcerated Persons
      (CAPSSIP) is a tool designed to assess protective factors and cultural barriers
      to suicide for inmates. We present initial findings on the reliability, validity,
      factor structure, and utility of the CAPSSIP based on a trial conducted with
      inmates sent to an inpatient psychiatric program. Implications for suicide risk
      assessment processes in correctional settings are discussed. (PsycINFO Database
      Record

PMID- 29022736
TI  - Preliminary evaluation of treatment outcomes at a military intensive outpatient
      program.
AB  - Recent U.S. Army policy has established intensive outpatient programs at several
      installations as part of a comprehensive behavioral health system of care. This
      study presents retrospective program evaluation data from a case series without
      randomization or a control group at 1 recently established intensive outpatient
      program for active duty service members at a joint military installation. Out of
      240 patients referred to the program at 1 installation, 200 enrolled in
      treatment. Of these, 169 completed treatment in a Skills & Resiliency Track (n =
      97), Trauma Track (n = 34), or both (Combined Track; n = 38). Patients completed
      measures of posttraumatic stress symptoms and general distress throughout program
      enrollment. First year preliminary results show significant decreases in distress
      for those in the Skills & Resiliency and Combined groups. Trauma group patients
      showed significant decreases in posttraumatic stress symptoms. Patients in the
      Skills & Resiliency and Combined groups showed significant decreases in rates of
      psychiatric hospitalization. These results show potential for treating high-risk
      or treatment-resistant patients in a half-day intensive outpatient program.
      Lessons learned and recommendations for establishing intensive outpatient
      programming for the military are discussed. (PsycINFO Database Record (c) 2018
      APA, all rights reserved).

PMID- 29022733
TI  - Person-centered approaches in the study of personality disorders.
AB  - Existing categorical models of personality disorder diagnoses capture
      heterogeneous populations in terms of symptom presentation and etiological
      influences on personality pathology. Though several well-validated alternative
      dimensional trait models (i.e., variable-centered approaches) of personality
      disorders have been developed, person-centered approaches can provide important
      additional information on both the phenotypic expression and etiology of
      personality pathology. We discuss the utility and necessary attributes of person
      centered or subtype models of personality disorders and briefly review
      statistical approaches and other methodological considerations, drawing specific
      examples from the psychopathy literature. We conclude by advocating a utilitarian
      approach whereby person-centered and variable-centered methods complement each
      other to better understand personality disorders. (PsycINFO Database Record

PMID- 29022737
TI  - Implementation of an integrative medicine treatment program at a Veterans Health
      Administration residential mental health facility.
AB  - A 4-week interdisciplinary integrative medicine program was recently added to the
      core treatment offerings for veterans participating in the Mental Health
      Residential Rehabilitation Program at the Dwight D. Eisenhower Veterans Affairs
      Medical Center. The new integrative medicine program teaches veterans about using
      meditative practices, nutrition, creative expression, tai chi, hatha yoga,
      sensory and breathing techniques, and lifestyle changes to enhance well-being.
      The groups are run by professionals from a variety of disciplines including
      recreation therapy, art therapy, occupational therapy, psychology, and nutrition.
      For the first 42 veterans to complete the program, the Short Form 12-item Health
      Survey was administered before and after participation in the integrative
      medicine program to assess the potential effectiveness of the program in
      enhancing physical and psychological well-being. In addition, a brief
      semistructured interview was used to assess veteran opinions about the program.
      Results suggest that the program was well received and that both physical and
      mental health scores improved from before to after treatment in this sample of
      veterans with complex behavioral health concerns. (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 29022738
TI  - An Exploration of the Symmetry Between Crime-Causing and Crime-Reducing Factors:
      Implications for Delivery of Offender Services.
AB  - Both the Risk-Needs-Responsivity (RNR) and Structured Professional Judgment (SPJ)
      risk assessment approaches assume that a strong relationship exists between crime
      causing and crime reducing factors. Using a probation sample, the present article
      examines whether crime-causing and crime-reducing factors correspond.
      Probationers completed questionnaires where they were asked what factors were
      crime-causing and what factors were crime-reducing. Overall, the relationship
      between the crime-causing and crime-reducing factors was very weak-even after
      ruling out potential measurement and methodological artifacts (i.e., internal
      consistency, item stability, and acquiescent responding). Applied to an
      individual offender, the results suggest that conducting assessments and
      recommending interventions need not be bound by assumptions that risk factors for
      past crime must be targeted to reduce crime. New endeavors to develop causal and
      idiographic crime-reducing strategies warrant consideration. (PsycINFO Database
      Record

PMID- 29022739
TI  - The Offender Job Search Self-Efficacy Scale: Development and initial validation.
AB  - The purpose of this study was to develop the Offender Job Search Self-Efficacy
      Scale (OFJSSE) for the specific job search needs of the criminal justice
      population. Participants were 249 male inmates within 2 years of release from a
      state correctional facility in the southern region of the United States who
      identified mostly as Caucasian (56.2%), single (62.2%), working-class (45.4%) men
      with a mean age of 36.27 years (SD = 10.38). Initial validation data are
      described, including results of an exploratory factor analysis. Results indicated
      that the OFJSSE presents excellent reliability (alpha = .95) as well as good
      convergent and discriminant validity by having a strong, positive correlation, r
      = .73, p < .01, with another job search scale and having a negative correlation,
      r = -.19, p = .01, with a scale measuring a different construct (i.e., criminal
      thinking). Implications of the findings as well as limitations and future
      directions are discussed. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 29022740
TI  - Long-Term Room Temperature Storage of Dry Ribonucleic Acid for Use in RNA-Seq
      Analysis.
AB  - RNA is an essential biological material for research in genomics and
      translational medicine. As such, its storage for biobanking is an important field
      of study. Traditionally, long-term storage in the cold (generally freezers or
      liquid nitrogen) is used to maintain high-quality (in terms of quantity and
      integrity) RNA. Room temperature (RT) preservation provides an alternative to the
      cold, which is plagued by serious problems (mainly cost and safety), for RNA long
      term storage. In this study, we evaluated the performance of several RT storage
      procedures, including the RNAshell(r) from Imagene, where the RNA is dried and
      kept protected from the atmosphere, and the vacuum drying of RNA with additives
      such as the Imagene stabilization solution and a home-made trehalose solution.
      This evaluation was performed through accelerated (equivalent to 10 years for
      RNAshell) aging and real-time studies (4 years). To check RNA quality and
      integrity, we used RNA integrity number values and RNA-seq. Our study shows that
      isolation from atmosphere offers a superior protective effect for RNA storage
      compared with vacuum drying alone, and demonstrates that RNAshell permits
      satisfactory RNA quality for long-term RT storage. Thus, the RNA quality could
      meet the demand of downstream applications such as RNA-seq.

PMID- 29022742
TI  - Culture-Based Quantification with Molecular Characterization of Non-O157 and O157
      Enterohemorrhagic Escherichia coli Isolates from Rectoanal Mucosal Swabs of
      Feedlot Cattle.
AB  - Enterohemorrhagic Escherichia coli (EHEC) strains are foodborne pathogens carried
      in the intestinal tracts of ruminants and shed in the feces. High concentrations
      (>=104 colony-forming units [CFU]/g) of EHEC in cattle feces are associated with
      contamination of hides, and subsequently, carcasses and beef. Several studies
      using agar media have quantified O157 but few have quantified non-O157 EHEC in
      samples from cattle. Thus, the objective of this study was to determine the
      concentration of O157 and non-O157 EHEC in cattle, and to characterize the
      associated EHEC isolates for their virulence potential. Two hundred feedlot
      steers were sampled by rectoanal mucosal swab (RAMS) every 35 days over four
      sampling periods, and a spiral plating method using modified Posse differential
      agar was used to quantify EHEC organisms in these samples. Bacterial colonies
      from agar plates were tested by multiplex PCR for Shiga toxin and intimin genes
      (stx and eae, respectively), and confirmed EHEC isolates (i.e., positive for both
      stx and eae) were serotyped and characterized for virulence genes using a
      microarray. Organisms detected in this study included O26, O101, O103, O109,
      O121, O145, O157, and O177 EHEC, with all except O121 quantifiable and measuring
      within a range from 9.0 * 102 to 3.0 * 105 CFU/g of RAMS sample. Organisms of the
      same EHEC serogroup were not detected in quantifiable concentrations from a
      single animal more than once. EHEC organisms most commonly detected at
      quantifiable levels were O26, O157, and O177. Interestingly, O26 EHEC isolates
      tested negative for stx1 but positive for stx2a. High concentrations of EHEC were
      detected in 11 (5.5%) of the steers at least once over the sampling period. These
      results indicate that in addition to O157, non-O157 EHEC are transiently present
      in high concentrations in the rectoanal mucosal region of cattle.

PMID- 29022741
TI  - Diagnostic accuracy of in-stent restenosis using model-based iterative
      reconstruction at coronary CT angiography: initial experience.
AB  - OBJECTIVE: The purpose of our study was to compare the diagnostic performance of
      coronary CT angiography (CTA) subjected to model-based iterative reconstruction
      (IR) or hybrid IR to rule out coronary in-stent restenosis. METHODS: We enrolled
      16 patients who harboured 22 coronary stents. They underwent coronary CTA on a
      320-slice CT scanner. The images were reconstructed with hybrid IR (AIDR 3D) and
      model-based IR (FIRST) algorithms. We calculated the stent lumen attenuation
      increase ratio and measured the visible stent lumen diameter. Two blinded
      observers visually graded the likelihood of in-stent restenosis (lesions >= 50%)
      on hybrid IR and FIRST images. RESULTS: The stent lumen attenuation increase
      ratio on FIRST- was lower than on AIDR 3D images (0.20 vs 0.32). The ratio of the
      visible- compared to the true stent lumen diameter was higher on FIRST- than AIDR
      3D images (52.5 vs 47.5%). Invasive coronary angiography identified five stents
      (22.7%) with significant in-stent restenosis. The use of FIRST improved the
      sensitivity (60 vs 100%), positive (75.0 vs 83.3%) and negative predictive value
      (88.9 vs 100%) and the accuracy (86.4 vs 95.5%) for the detection of in-stent
      restenosis. Specificity was 94.1% for both reconstruction methods. CONCLUSION:
      The model-based IR algorithm may improve diagnostic performance for the detection
      of in-stent restenosis. Advances in knowledge: Compared to hybrid IR, the new
      model-based IR algorithm reduced blooming artefacts and improved the image
      quality. It can be expected to improve diagnostic performance for the detection
      of in-stent restenosis on coronary CTA images.

PMID- 29022743
TI  - Non-invasive evaluation of stable renal allograft function using point shear-wave
      elastography.
AB  - OBJECTIVE: To investigate the feasibility of point shear-wave elastography (SWE)
      in evaluating patients with stable renal allograft function who underwent
      protocol biopsies. METHODS: 95 patients with stable renal allograft function that
      underwent ultrasound-guided biopsies at predefined time points (10 days or 1 year
      after transplantation) were enrolled. Ultrasound and point SWE examinations were
      performed immediately before protocol biopsies. Patients were categorized into
      two groups: subclinical rejection (SCR) and non-SCR. Tissue elasticity (kPa) on
      SWE was measured in the cortex of all renal allografts. RESULTS: SCR was
      pathologically confirmed in 34 patients. Tissue elasticity of the SCR group (31.0
      kPa) was significantly greater than that of the non-SCR group (24.5 kPa)
      (=0.016), while resistive index value did not show a significant difference
      between the two groups (p = 0.112). Tissue elasticity in renal allografts
      demonstrated significantly moderate negative correlation with estimated
      glomerular filtration rate (correlation coefficient = -0.604, p < 0.001). Tissue
      elasticity was not independent factor for SCR prediction on multivariate
      analysis. CONCLUSION: As a non-invasive tool, point SWE appears feasible in
      distinguishing between patients with SCR and without SCR in stable functioning
      renal allografts. Moreover, it may demonstrate the functional state of renal
      allografts. Advances in knowledge: On point SWE, SCR has greater tissue
      elasticity than non-SCR.

PMID- 29022744
TI  - A new lactam alkaloid from Portulaca oleracea L. and its cytotoxity.
AB  - A new lactam alkaloid named oleraciamide D (1), indentified as (5R)-4-(3-methoxy
      4-hydroxyphenyl)-5-(4-hydroxyphenyl)-5,6-dihydropyridin-2(1H)-one, together with
      five known compounds, indole-3-aldehyde (2), portulacatone (3), N-trans
      feruloyloctopamine (4), N-trans-feruloyl-3'-O-methyldopamine (5) and N-trans
      feruloyltyramine (6) were isolated from Potulaca oleracea L. Among them, indole-3
      aldehyde (2) was isolated from the medicine for the first time. The structure of
      the new alkaloid was elucidated via UHPLC-ESI-Q-TOF/MS, 1D NMR and 2D NMR. The
      five known compounds were established by comparing the 1H-NMR and 13C NMR with
      the reported literature. Oleraciamide D (1) showed cytotoxicity against SH-SY5Y
      cells when concentration at 50 uM by CCK-8 method.

PMID- 29022745
TI  - Real world adherence to oral anticoagulant in non-valvular atrial fibrillation
      patients in China.
AB  - BACKGROUND AND OBJECTIVE: Adherence to oral anticoagulants is crucial for the
      prevention of ischemic stroke in atrial fibrillation patients; however, evidence
      of oral-anticoagulant adherence from developing countries is still lacking. This
      study aimed to evaluate the current situation and predictors of oral
      anticoagulant adherence in non-valvular atrial fibrillation (NVAF) patients in
      China. METHODS: Records of NVAF patients were obtained from a regional claims
      database. Both initiation and adherence to oral anticoagulants were calculated
      from linked records. Factors of oral-anticoagulant initiation were identified
      using Cox regression. RESULTS: Among 33,463 NVAF patients, only 13.9% initialized
      warfarin treatment after the indexed hospital visit. Stratified by CHA2DS2-VASc
      scores, 20.9% of patients in the low-risk group were on warfarin, followed by
      15.3% and 10.7% from the middle and high-risk groups, respectively. Among
      patients who initialized warfarin, only 40.4% filled the first repeat
      prescription within 3 months. Concurrent statin use, hypertension and heart
      failure were associated with higher warfarin initiation rate. Factors such as age
      above 75, female sex, manufacture workers, discharge from the primary-care
      center, antiplatelet use, and diabetes, ischemic and hemorrhagic stroke were
      associated with lower rate of warfarin initiation. Additionally, initiating
      warfarin treatment reduced risk of ischemic stroke in middle and high-risk
      patients. CONCLUSION: Oral anticoagulation was significantly under-used in NVAF
      patients in China. Age, sex, concurrent drug usage, and disease history were
      associated factors. Improving warfarin adherence was promising to reduce ischemic
      stroke risk of NVAF patients.

PMID- 29022746
TI  - Achieving the composite endpoint of HbA1c, body weight, and systolic blood
      pressure reduction with canagliflozin in patients with type 2 diabetes.
AB  - OBJECTIVE: In addition to achieving glycemic control, weight loss and blood
      pressure (BP) reduction are important components of type 2 diabetes mellitus
      (T2DM) management, as many patients with T2DM are overweight/obese and/or have
      hypertension. Canagliflozin, an SGLT2 inhibitor, has demonstrated improvements in
      HbA1c, body weight (BW), and systolic BP across a broad range of patients with
      T2DM. This analysis evaluated achievement of composite endpoints of HbA1c, BW,
      and systolic BP targets with canagliflozin versus placebo. METHODS: This post hoc
      analysis evaluated the proportion of T2DM patients achieving the composite
      endpoint of HbA1c reduction >=0.5%, BW reduction >=3%, and systolic BP reduction
      >=4mmHg with canagliflozin 100 and 300mg compared with placebo using pooled data
      from four 26-week, phase 3 studies (N = 2313; NCT01081834, NCT01106677,
      NCT01106625, NCT01106690). The proportion of patients achieving the composite
      endpoint of HbA1c <7.0%, BW reduction >=3%, and BP <130/80 mmHg was also
      evaluated. RESULTS: At week 26, greater proportions of patients met individual
      HbA1c, BW, and systolic BP targets with canagliflozin versus placebo. A greater
      proportion of patients treated with canagliflozin 100 or 300 mg versus placebo
      also achieved the composite endpoint of HbA1c reduction >=0.5%, BW reduction
      >=3%, and systolic BP reduction >=4 mmHg at week 26 (21.1%, 25.3%, and 5.7%,
      respectively; odds ratios [95% CI] of 4.5 [3.1, 6.5] and 5.6 [3.8, 8.2]). A
      greater proportion of patients also achieved the composite endpoint of HbA1c
      <7.0%, BW reduction >=3%, and BP <130/80 mmHg with canagliflozin 100 and 300 mg
      versus placebo (14.7%, 20.9%, and 3.3%, respectively; odds ratios [95% CI] of 5.2
      [3.2, 8.4] and 8.4 [5.2, 13.5]). Canagliflozin was generally well tolerated, with
      a safety profile similar to that seen in other phase 3 studies. CONCLUSIONS:
      Patients with T2DM were more likely to achieve clinically important reductions in
      HbA1c, BW, and systolic BP with canagliflozin versus placebo.

PMID- 29022747
TI  - FDG-PET/CT findings of chronic active Epstein-Barr virus infection.

PMID- 29022748
TI  - Dependence of volume calculation and margin growth accuracy on treatment planning
      systems for stereotactic radiosurgery.
AB  - OBJECTIVE: Uncertainties in radiotherapy target structures are partly dependent
      on differences between volume calculation and margin growing methods in treatment
      planning systems (TPS). These uncertainties are exacerbated with very small
      structures such as those common in stereotactic radiosurgery. METHODS: Data from
      a national commissioning programme for SRS was used to assess variation in
      reported volumes for six benchmark cases, including malignant and benign
      indications. Reported volumes were compared both with and without any margins
      added according to local practice. RESULTS: 137 plans were submitted, with a
      total of 311 structures and covering seven TPS. For volumes < 1 cm3 agreement was
      within 0.05 cm3, and for volumes > 1 cm3 agreement was within 5%. Systematic
      differences were seen between TPS, partly because of different methods for
      calculating the end slice volume. About one third of structures had a margin
      added, of 1-2 mm. Most TPS over-grew the volumes, compared to the approximation
      of a perfect sphere, especially Pinnacle and Eclipse. CONCLUSION: Differences
      between volume calculation methods may lead to 5-10% variation in reported
      volumes from different TPS. This should be taken into account when comparing
      multicentre studies, and it is recommended that a minimum volume of 0.05 cm3 be
      used for any near-point doses to allow more consistent comparisons. When margins
      are added to small structures, there may be up to 40% difference to nominal
      margin size. Such differences are still small compared to interobserver variation
      in delineation. Advances in knowledge: This study quantifies the potential
      uncertainties in clinical volume calculation and margin growth with small
      radiosurgical targets.

PMID- 29022749
TI  - Pediatric precursor B-cell acute lymphoblastic leukemia with MYC 8q24
      translocation - how to treat?
AB  - Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Within
      ALL, precursor B-cell disease predominates and now has survival >90%. Mature B
      cell, or Burkitt leukemia/lymphoma, is distinct from ALL and requires short
      intensive chemotherapy and with the addition of Rituximab, survival rates of >95%
      are achieved. Its defining characteristic is MYC translocation at 8q24. Patients
      who have features of both ALL and Burkitt leukemia/lymphoma represent a rare
      subpopulation of ALL and present a diagnostic and treatment conundrum. We have
      performed a systematic review on the occurrence of and treatment of MYC positive
      precursor B-ALL, reported between 1980 and 2016. The review highlighted a lack of
      data to guide any consensus about how to treat this important group of children
      and focused research in this area is needed.

PMID- 29022750
TI  - The cost-effectiveness of therapies to treat alcohol use disorders.
AB  - INTRODUCTION: Alcohol use is a major risk factor for mortality and morbidity
      burden, and alcohol use disorders contribute markedly to this burden. Effective
      interventions for alcohol use disorders improve health, and are potentially cost
      effective or even cost saving. Areas covered: We searched the literature for the
      cost-effectiveness of alcohol interventions. We included behavioral,
      pharmacological and combined interventions, and research from both a health care
      provider and a societal perspective. Overall, many economic research studies
      pointed towards existing cost-beneficial therapies from the perspective of a
      health care provider; i.e. the costs for interventions were smaller than the
      savings in services delivery in the years thereafter. Even if this was not the
      case, the interventions proved to be cost-effective with a threshold below
      $20,000 per quality-adjusted life year. Expert Commentary: While most of the
      economic research to date shows promising results, such research is relatively
      scarce and not always rigorous. More, and more rigorous economic research is
      needed to fully understand the potential impact of alcohol interventions.
      However, even with this research, something needs to be done to reduce
      stigmatization of alcohol use disorders in order to fully reap the benefits of
      alcohol interventions.

PMID- 29022752
TI  - Nutritional Characteristics of the Diets of Child and Adolescent Cancer
      Survivors.
AB  - PURPOSE: Diseases associated with prior treatment, such as obesity, have been
      described in cancer survivors. Recent studies have shown that current estimates
      of overweight do not differ from that in the general population, suggesting the
      influence of environmental factors, such as dietary intake. In this context,
      there is increasing interest in the examination of health behaviors that may
      modify and reduce the risk of overweight and obesity. This study aimed to
      evaluate the characteristics of dietary intake among child cancer survivors
      living in a developing country. METHODS: This retrospective cross-sectional study
      included children and adolescents up to 18 years of age. Dietary intake of the
      patients was assessed using 24-hour dietary recall. RESULTS: All age groups
      showed sufficient carbohydrate and protein consumption levels. The mean
      percentages of carbohydrate and protein consumption were 54% and 20.8%,
      respectively. Regarding lipid quality, survivors showed low consumption levels of
      polyunsaturated and monounsaturated fats. The consumption level of saturated fats
      was close to the upper limit. Fiber intake was below the recommended level in all
      patient categories, and its mean was 11.5 g/day. The average daily intake of some
      vitamins and minerals was below the recommended intake levels for all sexes and
      age groups, with values below 50% of suitability. CONCLUSION: The imbalance of
      lipids quality and low consumption of micronutrients demonstrated that the diet
      quality is poor in child cancer survivors. This favors the development of not
      only obesity but also other chronic diseases, and potentially predisposes such
      patients to secondary cancers. IMPLICATIONS FOR CANCER SURVIVORS: this is a
      relevant issue due to the increased number of childhood cancer survivors who
      develop obesity and chronic and metabolic complications due to inadequate food
      consumption. Our study may help understand, prevent, or minimize public health
      problems.

PMID- 29022751
TI  - Prospective psychometric characterization of hip and knee arthroplasty patients.
AB  - BACKGROUND: Psychiatric conditions and psychopharmacological treatments have been
      demonstrated to be important risk-factors for prolonged hospital length of stay,
      readmission and morbidity, following fast-track total hip (THA) and total knee
      arthroplasty (TKA). AIMS: The aim of the study was to provide a detailed
      description of the preoperative psychiatric characteristics of a well-defined
      patient population undergoing THA and TKA, using the 90-item Symptom Checklist
      (SCL-90-R). METHODS: A pre-surgical population of 2183 patients completed the
      full SCL-90-R prior to THA/TKA from 2015 to 2016. The SCL-90-R scale and total
      scores of the pre-surgical sample were compared to the scores of an age- and
      gender stratified Danish sample of healthy controls. A Mokken scalogram analysis
      was conducted to assess the scalability of the SCL-90-R in both samples. RESULTS:
      The Mokken analysis yielded acceptable scalability coefficients above 0.30 in all
      subscales of the SCL-90-R except psycoticism (0.28). There was no clinically
      significant difference (effect size = <0.50) in the SCL-90-R total score between
      the pre-surgical and the healthy controls samples, although pre-surgical patients
      had lower mean scores compared to the healthy controls in all subscales except
      somatization (effect size = -0.22). CONCLUSION: The Mokken analysis demonstrated
      that the SCL-90-R and its subscales express valid measures of psychopathology in
      our surgical sample. The psychiatric profile of the pre-surgical patient sample
      indicates that patients undergoing THA/TKA are not more burdened by psychiatric
      symptoms than a healthy control group with the exception of symptoms relating to
      somatization.

PMID- 29022753
TI  - Lower heart rate variability at baseline is associated with more consecutive
      intrusive memories in an experimental distressing film paradigm.
AB  - OBJECTIVES: First evidence suggests that lower heart rate variability (HRV) is
      associated with more cognitive control deficits, a risk factor for the
      development of intrusive memories. The aim of this study was to determine whether
      high-frequency (HF) and low-frequency/high-frequency (LF/HF) ratio components of
      HRV at rest before an intrusion-inducing stressor would predict consecutive
      intrusive memories. METHODS: Healthy female participants (n = 60) watched an
      established distressing film which induced intrusions. HF and LF/HF ratio were
      measured for 5 min prior to the stressor. The number of consecutive intrusions
      resulting from the distressing film was assessed throughout the following 4 days.
      RESULTS: The main effect LF/HF ratio was associated with more intrusive memories,
      whereas, the main effect HF was associated with more intrusions on a trend level.
      The time * HF and time * LF/HF ratio interactions were significant, indicating a
      different course of number of intrusions over the 4 days depending on HF and
      LF/HF ratio. The regression-based parameter estimates revealed a significant
      association of lower HF and number of intrusions on days 1 and 2 and a
      significant association of higher LF/HF (i.e. lower HRV) and number of intrusions
      on day 1. CONCLUSIONS: The results suggest that higher baseline LF/HF ratio (i.e.
      lower HRV) predicts more intrusive memories in healthy women after watching a
      distressing film. Furthermore, the results suggest that women with lower baseline
      HF and higher LF/HF ratio recover at a slower rate from watching the distressing
      film by showing a delayed decrease in intrusive memories. Our findings support
      the notion that lower baseline HRV before a trauma might be a vulnerability
      factor for subsequent intrusive memories.

PMID- 29022754
TI  - Different Protocols of Photobiomodulation Therapy of Hyposalivation.
AB  - OBJECTIVE: Photobiomodulation (PBM) therapy has proved to be effective for a wide
      range of oral pathologies including oral dryness, but the literature still lacks
      reports of clinical trials and protocols. The purpose of our study was to
      evaluate the effects of different wavelengths of PBM on salivation in patients
      suffering from hyposalivation aiming at determination of optimal treatment
      protocol. MATERIALS AND METHODS: This study included 30 patients whose major
      salivary glands were treated with low-intensity diode laser BTL2000 (Medical
      Technologies, s.r.o., Czech Republic) during 10 consecutive days. Patients were
      randomly assigned into two groups, each of 15 patients, and treated with PBM of
      830 nm and PBM of 685 nm, respectively. The whole unstimulated and stimulated
      saliva quantities were measured each day during 10 days, before and after laser
      treatment, and at 10th day after treatment was ended. RESULTS: Results have shown
      that the laser treatment significantly improves salivation (p < 0.0001) in both
      groups after 10 days treatment. The salivation also remains improved 10 days
      after the end of treatment. The patients treated with PBM of 830 nm have had
      continuously higher values of quantity of saliva. CONCLUSIONS: Our results have
      shown that both laser wavelengths were effective in increasing salivary flow
      rate, and the improvement in salivation was statistically significant. The effect
      of treatment could be observed 10 days after the completion of treatment, thus
      providing evidence not only of stimulative effect but also indicating
      regenerative potential of PBM therapy.

PMID- 29022755
TI  - Randomized, double-blind, placebo-controlled, parallel-group, multi-center study
      of the safety and efficacy of ADAM zolmitriptan for the acute treatment of
      migraine.
AB  - Objective To determine the efficacy, tolerability, and safety of ascending doses
      of Adhesive Dermally-Applied Microarray (ADAM) zolmitriptan versus placebo for
      acute migraine treatment. Background ADAM is a novel patient-administered system
      for intracutaneous drug administration. In a phase 1 pharmacokinetic study,
      zolmitriptan administered using ADAM had much faster absorption than oral
      administration with higher exposure in the first two hours. Methods This was a
      multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase
      2b/3 study evaluating ADAM zolmitriptan 1 mg, 1.9 mg, and 3.8 mg versus placebo.
      Co-primary endpoints were pain freedom and freedom from most bothersome other
      migraine-associated symptom 2 hours post-dose. Results Of patients treated with
      ADAM zolmitriptan 3.8 mg or placebo, 41.5% and 14.2%, respectively were pain-free
      2 hours post-dose ( p = 0.0001) and 68.3% and 42.9% were free from their most
      bothersome other symptom ( p = 0.0009). Due to the fixed sequential testing
      methodology, formal statistical significance was not established for secondary
      endpoints. However, the proportion of patients who were photophobia-free,
      phonophobia-free, and nausea-free at 2 hours post-dose was higher in the ADAM
      zolmitriptan 3.8 mg group compared with placebo, as were the percentages of
      patients who were pain-free, and who experienced pain relief up to 48 hours post
      dose. Systemic adverse events were consistent with previous triptan trials, and
      included dizziness, paresthesia, muscle tightness, and nausea, all of which
      occurred in < 5% of patients in any group. Application site reactions were
      generally mild and resolved within 48 hours, although erythema and bruising
      persisted for longer periods in some patients. Conclusion ADAM zolmitriptan 3.8
      mg provides effective relief of migraine headache and associated most bothersome
      symptoms compared with placebo, and is well-tolerated. ClinicalTrials.gov
      NCT02745392.

PMID- 29022757
TI  - World conference special.

PMID- 29022756
TI  - Soluble guanylyl cyclase is a critical regulator of migraine-associated pain.
AB  - Background Nitric oxide (NO) has been heavily implicated in migraine.
      Nitroglycerin is a prototypic NO-donor, and triggers migraine in humans. However,
      nitroglycerin also induces oxidative/nitrosative stress and is a source of
      peroxynitrite - factors previously linked with migraine etiology. Soluble
      guanylyl cyclase (sGC) is the high affinity NO receptor in the body, and the aim
      of this study was to identify the precise role of sGC in acute and chronic
      migraine. Methods We developed a novel brain-bioavailable sGC stimulator (VL
      102), and tested its hyperalgesic properties in mice. We also determined the
      effect of VL-102 on c-fos and calcitonin gene related peptide (CGRP)
      immunoreactivity within the trigeminovascular complex. In addition, we also
      tested the known sGC inhibitor, ODQ, within the chronic nitroglycerin migraine
      model. Results VL-102-evoked acute and chronic mechanical cephalic and hind-paw
      allodynia in a dose-dependent manner, which was blocked by the migraine
      medications sumatriptan, propranolol, and topiramate. In addition, VL-102 also
      increased c-fos and CGRP expressing cells within the trigeminovascular complex.
      Importantly, ODQ completely inhibited acute and chronic hyperalgesia induced by
      nitroglycerin. ODQ also blocked hyperalgesia already established by chronic
      nitroglycerin, implicating this pathway in migraine chronicity. Conclusions These
      results indicate that nitroglycerin causes migraine-related pain through
      stimulation of the sGC pathway, and that super-activation of this receptor may be
      an important component for the maintenance of chronic migraine. This work opens
      the possibility for negative sGC modulators as novel migraine therapies.

PMID- 29022759
TI  - No change in scope for extension of patent term for pharmaceutical substances
      under Australian law: an update.

PMID- 29022758
TI  - Pharmacokinetic Profiling of Conjugated Therapeutic Oligonucleotides: A High
      Throughput Method Based Upon Serial Blood Microsampling Coupled to Peptide
      Nucleic Acid Hybridization Assay.
AB  - Therapeutic oligonucleotides, such as small interfering RNAs (siRNAs), hold great
      promise for the treatment of incurable genetically defined disorders by targeting
      cognate toxic gene products for degradation. To achieve meaningful tissue
      distribution and efficacy in vivo, siRNAs must be conjugated or formulated. Clear
      understanding of the pharmacokinetic (PK)/pharmacodynamic behavior of these
      compounds is necessary to optimize and characterize the performance of
      therapeutic oligonucleotides in vivo. In this study, we describe a simple and
      reproducible methodology for the evaluation of in vivo blood/plasma PK profiles
      and tissue distribution of oligonucleotides. The method is based on serial blood
      microsampling from the saphenous vein, coupled to peptide nucleic acid
      hybridization assay for quantification of guide strands. Performed with minimal
      number of animals, this method allowed unequivocal detection and sensitive
      quantification without the need for amplification, or further modification of the
      oligonucleotides. Using this methodology, we compared plasma clearances and
      tissue distribution profiles of two different hydrophobically modified siRNAs
      (hsiRNAs). Notably, cholesterol-hsiRNA presented slow plasma clearances and
      mainly accumulated in the liver, whereas, phosphocholine-docosahexaenoic acid
      hsiRNA was rapidly cleared from the plasma and preferably accumulated in the
      kidney. These data suggest that the PK/biodistribution profiles of modified
      hsiRNAs are determined by the chemical nature of the conjugate. Importantly, the
      method described in this study constitutes a simple platform to conduct pilot
      assessments of the basic clearance and tissue distribution profiles, which can be
      broadly applied for evaluation of new chemical variants of siRNAs and micro-RNAs.

PMID- 29022760
TI  - Terpenoids from the barks of Magnolia maudiae (Dunn) Figlar.
AB  - A new germacrenolide (1) and fourteen known terpenoids (2-15) were isolated from
      the barks of Magnolia maudiae (Dunn) Figlar (Magnoliaceae). The structure of
      (7alphaH,11betaH)-2alpha,8alpha-dihydroxy-4alpha,5beta-epoxy-germacr-1(10)-en
      6alpha,12-olide (1) was elucidated by physical and spectroscopic data analysis,
      including 1D, 2D NMR and HR-ESI-MS. Lyratol F (9) was isolated from Magnolia for
      the first time. The structures of known compounds were established by comparing
      their spectroscopic data with those in literatures.

PMID- 29022762
TI  - Polymorphism rs11656696 in GAS7 Is Not Associated with Primary Open Angle
      Glaucoma in a Saudi Cohort.
AB  - AIMS: To conduct a case-control study to investigate the association between the
      polymorphism rs11656696 located in the growth arrest-specific 7 gene (GAS7)on
      human chromosome 17p13.1 and primary open angle glaucoma (POAG). METHODS: The
      polymorphism rs11656696 was genotyped using the TaqMan(r) assay in 187 subjects
      comprising 92 unrelated POAG cases and 95 controls of Saudi Arabian origin.
      RESULTS: Association analysis between cases and controls revealed no significant
      genotype distribution under additive (p = 0.225), dominant (p = 0.635), or
      recessive (p = 0.085) models. Moreover, the allele frequency distribution was
      also nonsignificant (p = 0.70). The minor "A" allele frequency was 0.35 and 0.41
      among POAG cases and controls, respectively. In addition, specific clinical
      indices used to assess severity of glaucoma such as intraocular pressure (IOP),
      cup/disk ratio, and number of antiglaucoma medications also did not show any
      significant genotype distribution in POAG cases. Moreover, a binary logistic
      regression analysis did not show any significant effect of age, sex, or genotype
      on disease outcome. CONCLUSION: Polymorphism rs11656696 is not associated with
      POAG nor any of its endophenotypic traits such as IOP and cup/disk ratio and is
      thus not a risk factor for POAG in this Saudi cohort.

PMID- 29022761
TI  - Noninvasive Ocular Drug Delivery System of Dexamethasone Sodium Phosphate in the
      Treatment of Experimental Uveitis Rabbit.
AB  - PURPOSE: To investigate the efficacy and safety of dexamethasone sodium phosphate
      administered through Visulex system (DSP-Visulex) in treating experimental
      uveitis. METHODS: Uveitis was induced in rabbits by subcutaneous injections of
      complete Freund's adjuvant and an intravitreal injection of H37RA antigen. After
      induction, the animals of the control group received no treatment and the others
      received various treatment regimens of DSP-Visulex. Each regimen was different in
      DSP strength (4%, 8%, and 15%), application time, or treatment frequency.
      Efficacy and safety of DSP-Visulex were evaluated by ophthalmic observations and
      histopathological examinations for ocular inflammations and pathology. RESULTS:
      The control group exhibited panuveitis with significant inflammation in the
      vitreous, choroid, and retina, but less in the conjunctiva, cornea, and anterior
      chamber. The uveitis occurred within 24 h after induction and persisted
      throughout the study in the control group. All treatments showed some reduction
      in inflammation in the vitreous, choroid, and retina. The higher dose regimens
      generally showed more rapid and higher degree of resolution than the lower dose
      regimens. The posterior eye tissues of the 15% and 8% DSP-Visulex appeared normal
      with minimal or no inflammation, whereas the untreated eye and the 4% DSP-Visulex
      eyes showed minimal response. CONCLUSIONS: All DSP-Visulex regimens suppressed
      the signs of inflammation and were well tolerated over the course of a 29-day
      study. The 8% and 15% DSP-Visulex treatment regimens were safe and efficacious
      for anterior, intermediate, and posterior uveitis. On the other hand, the 4% DSP
      Visulex regimen may only be considered for anterior and intermediate uveitis.

PMID- 29022764
TI  - Proteasome and C-reactive protein inflammatory response in children undergoing
      shorter and longer lasting laparoscopic cholecystectomy.
AB  - Operations of varying duration cause the release of a number of inflammatory
      mediators, in particular cytokines which lead to proteasome and acute-phase
      reactions. The purpose of this novel human study, was to characterize
      inflammatory response in children undergoing laparoscopic cholecystectomy, by
      analyzing changes in selected inflammatory mediators: C-reactive protein
      concentration and circulating 20S proteasome activity following surgical injury
      and to correlate them with the duration of the surgical procedure. Plasma C
      reactive protein concentration (CRP) was determined by standard biochemical
      laboratory procedures. Proteasome activity in the plasma of children was assessed
      using Suc-Leu-Leu-Val-Tyr-AMC peptide substrate. Statistically significant
      increase in the plasma proteasome activity and C-reactive protein concentration,
      was noted (p < .05) in children after laparoscopic cholecystectomy. We found the
      correlation between the 20S proteasome activity and the length of the procedure.
      In children undergoing longer lasting laparoscopic cholecystectomy the proteasome
      activity was much higher than in patients having shorter surgical procedure. The
      CRP concentration and 20S proteasome activity significantly increase after
      surgery, but only 20S proteasome activity correlate with the length of the
      surgery. This may confirm that CRP is only an indicator of pathological state,
      while the function of the proteasomes is more complex because of their
      participation in the processes of repair and wound healing, and in the removal of
      damaged proteins.

PMID- 29022763
TI  - Impact of practice, provider and patient characteristics on delivering screening
      and brief advice for heavy drinking in primary healthcare: Secondary analyses of
      data from the ODHIN five-country cluster randomized factorial trial.
AB  - BACKGROUND: The implementation of primary healthcare-based screening and advice
      that is effective in reducing heavy drinking can be enhanced with training.
      OBJECTIVES: Undertaking secondary analysis of the five-country ODHIN study, we
      test: the extent to which practice, provider and patient characteristics affect
      the likelihood of patients being screened and advised; the extent to which such
      characteristics moderate the impact of training in increasing screening and
      advice; and the extent to which training mitigates any differences due to such
      characteristics found at baseline. METHODS: A cluster randomized factorial trial
      involving 120 practices, 746 providers and 46 546 screened patients from
      Catalonia, England, the Netherlands, Poland, and Sweden. Practices were
      randomized to receive training or not to receive training. The primary outcome
      measures were the proportion of adult patients screened, and the proportion of
      screen-positive patients advised. RESULTS: Nurses tended to screen more patients
      than doctors (OR = 3.1; 95%CI: 1.9, 4.9). Screen-positive patients were more
      likely to be advised by doctors than by nurses (OR = 2.3; 95%CI: 1.4, 4.1), and
      more liable to be advised the higher their risk status (OR = 1.9; 95%CI: 1.3,
      2.7). Training increased screening and advice giving, with its impact largely
      unrelated to practice, provider or patient characteristics. Training diminished
      the differences between doctors and nurses and between patients with low or high
      risk status. CONCLUSIONS: Training primary healthcare providers diminishes the
      negative impacts that some practice, provider and patient characteristics have on
      the likelihood of patients being screened and advised. Trial registration
      ClinicalTrials.gov. Trial identifier: NCT01501552.

PMID- 29022765
TI  - Polymorphisms in genes involved in vasoactive eicosanoid synthesis affect
      cardiovascular risk in renal transplant recipients.
AB  - OBJECTIVE: Arachidonic acid metabolism by cytochrome P450 (CYP) epoxygenases
      leads to epoxyeicosatrienoic acids (EETs), which are eicosanoids with vasodilator
      and anti-inflammatory properties. We aim to determine whether genetic variability
      in these routes may contribute to cardiovascular (CV) risk in renal transplant
      recipients. METHODS: In a cohort of 355 patients, we determined the presence of
      two polymorphisms, CYP2C8*3 and CYP2J2*7, known to affect eicosanoid levels.
      Associations with CV mortality, CV event-free long-term survival and graft
      survival were retrospectively investigated by logistic regression models.
      RESULTS: CYP2J2*7 showed a statistical trend towards higher CV mortality (p =
      .06) and lower cardiac or cerebral event-free long-term survival (p = .05),
      whilst CYP2C8*3 displayed a significant inverse association with the risk of CV
      event (hazard ratio [HR] = 0.34 [0.15-0.78], p = .01). The association of
      CYP2J2*7 with CV mortality became significant when the analysis was restrained to
      316 patients without a history of CV events prior to transplantation (HR = 15.72
      [2.83-91.94], p = .005). In this subgroup of patients both single nucleotide
      polymorphisms (SNPs) were significantly associated with event-free survival. HR
      values were 5.44 (1.60-18.51), p = .007 and 0.26 (0.09-0.75), p = .012 for
      CYP2J2*7 and CYP2C8*3, respectively. CONCLUSIONS: Our results show, for the first
      time to our knowledge, that two SNPs in CYP2C8 and CYP2J2, which synthesize EETs,
      may modify CV outcomes in renal transplant recipients, a population that is
      already at a high risk of suffering these events.

PMID- 29022766
TI  - A solution-focused approach to understanding patient motivation in diabetes self
      management: Gender differences and implications for primary care.
AB  - OBJECTIVE: Healthcare providers often neglect to recognize the role they play in
      motivating patients with diabetes to perform self-management. Our aims were to
      understand what motivates patients with diabetes to implement recommended self
      management practices and understand the role of the primary care team in patient
      motivation. METHODS: We use a solution-focused qualitative approach, supplemented
      with a quantitative scale. We used a purposive sampling strategy to invite
      patients with uncontrolled diabetes. Semi-structured telephone interviews were
      conducted and analyzed using content and thematic analysis. RESULTS: Key
      motivators were strong support systems that included family and friends, the
      physician's communication style and message, fear of deterioration, and other
      intrinsic factors. Female family members were described as supportive; not all
      married women felt supported by their husbands. Women were more influenced by
      empathy and concern from their doctor, compared to men who were motivated by
      improved health literacy. Women with few family or friends were more
      disadvantaged, regardless of race/ethnicity. DISCUSSION: While physicians play a
      vital role in motivating their patients, female patients may depend on this
      empathy more than males. The interdisciplinary care team can play an important
      role in helping patients create a support network where it may not exist.

PMID- 29022767
TI  - alpha-Glucosidase inhibitory and cytotoxic botryorhodines from mangrove
      endophytic fungus Trichoderma sp. 307.
AB  - One new depsidone, botryorhodine H (1), together with three known analogues,
      botryorhodines C, D and G (2-4), were obtained from the mangrove endophytic
      fungus Trichoderma sp. 307 by co-culturing with Acinetobacter johnsonii B2.
      Structures were determined by 1D and 2D NMR analyses and high-resolution mass
      spectrum. Compounds 1-3 showed alpha-glucosidase inhibitory activity with IC50
      ranging from 8.1 to 11.2 MUM, and compound 1 exhibited potent cytotoxicity
      against rat prolactinoma MMQ and rat pituitary adenoma GH3 cell lines (IC50 =
      3.09 and 3.64 MUM).

PMID- 29022769
TI  - Aiming for Quality Improvement: Aligning Population Health and Higher Education.

PMID- 29022770
TI  - Exploring Adolescents' Cancer Journey Through Photovoice: A Narrative Synthesis.
AB  - PURPOSE: Photovoice is a novel and promising intervention for working with youth
      in healthcare settings. Despite this, few studies have examined the efficacy of
      photovoice as a clinical tool for working with teenagers who are on their cancer
      journey. To better understand the needs of teenagers with cancer and the ways
      that photovoice can be utilized to address these needs, a systematic review of
      the literature was undertaken. METHODS: Keyword searches of six databases were
      completed, including MEDLINE, EMBASE, PsycINFO, Social Work Abstracts,
      Sociological Abstracts, and Health and Psychosocial Instruments. Searches were
      limited to articles focusing on the psychosocial needs of adolescents, aged 13
      17, who were on active cancer treatment. RESULTS: Sixty-four articles were
      identified that discussed the psychosocial needs of teenagers on active cancer
      treatment. The needs of these teenagers can be understood as being influenced by
      the physical changes and symptoms, psychological impact of diagnosis and
      treatment, short- and long-term social impacts of cancer, impact on holistic well
      being, and need for clear, age-appropriate communication. Among these articles,
      only four articles used photovoice as a methodology and none examined the impact
      of photovoice as an intervention for teenagers who were currently on active
      treatment. CONCLUSION: Photovoice is uniquely positioned among other psychosocial
      interventions to help address the needs of teenagers on their cancer journey.
      Despite this, few researchers have examined the efficacy of photovoice as a
      psychosocial intervention for teenagers who are currently on active treatment.

PMID- 29022768
TI  - Molecular Survey on Rickettsia spp., Anaplasma phagocytophilum, Borrelia
      burgdorferi Sensu Lato, and Babesia spp. in Ixodes ricinus Ticks Infesting Dogs
      in Central Italy.
AB  - Dogs are a common feeding hosts for Ixodes ricinus and may act as reservoir hosts
      for zoonotic tick-borne pathogens (TBPs) and as carriers of infected ticks into
      human settings. The aim of this work was to evaluate the presence of several
      selected TBPs of significant public health concern by molecular methods in I.
      ricinus recovered from dogs living in urban and suburban settings in central
      Italy. A total of 212 I. ricinus specimens were collected from the coat of
      domestic dogs. DNA was extracted from each specimen individually and tested for
      Rickettsia spp., Borrelia burgdorferi sensu lato, Babesia spp., and Anaplasma
      phagocytophilum, using real-time and conventional PCR protocols, followed by
      sequencing. Sixty-one ticks (28.8%) tested positive for TBPs; 57 samples were
      infected by one pathogen, while four showed coinfections. Rickettsia spp. was
      detected in 39 specimens (18.4%), of which 32 were identified as Rickettsia
      monacensis and seven as Rickettsia helvetica. Twenty-two samples (10.4%) tested
      positive for A. phagocytophilum; Borrelia lusitaniae and Borrelia afzelii were
      detected in two specimens and one specimen, respectively. One tick (0.5%) was
      found to be positive for Babesia venatorum (EU1). Our findings reveal the
      significant exposure of dogs to TBPs of public health concern and provide data on
      the role of dogs in the circulation of I. ricinus-borne pathogens in central
      Italy.

PMID- 29022771
TI  - Lateral orbitofrontal cortex activity is modulated by group membership in
      situations of justified and unjustified violence.
AB  - The role of the orbitofrontal cortex (OFC) in moral decision-making is well
      established. However, OFC activity is highly context dependent. It is affected by
      the extent to which choices are morally justified and whom they concern. In the
      current study, we specifically focus on contextual factors and investigate the
      differential role of the OFC during justified and unjustified violence towards
      ingroup versus outgroup members. Muslims were chosen as the outgroup, as they are
      currently stereotypically seen as an outgroup and a potential threat by some Non
      Muslims. Importantly, we also introduce a context where participants are the
      actual agents responsible for doing harm. During fMRI scanning, Non-Muslim
      participants had to decide to either shoot a Non-Muslim (i.e., ingroup member) or
      Muslim (outgroup member) depending on whether they believed the target was
      holding a gun or an object. Neuroimaging results showed increased activation in
      the lateral OFC (lOFC) in the three contrasts that were distressing: 1) during
      unjustifiable killing; 2) when being killed; and 3) when confronted by an
      outgroup member with a gun. Together, these results provide important insights
      into the neurocognitive mechanisms involved in intergroup violence and highlight
      the critical role of the lOFC in context dependent social decision-making.

PMID- 29022772
TI  - Formulation and delivery strategies of ibuprofen: challenges and opportunities.
AB  - Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is mostly administered
      orally and topically to relieve acute pain and fever. Due to its mode of action
      this drug may be useful in the treatment regimens of other, more chronic
      conditions, like cystic fibrosis. This drug is poorly soluble in aqueous media
      and thus the rate of dissolution from the currently available solid dosage forms
      is limited. This leads to poor bioavailability at high doses after oral
      administration, thereby increasing the risk of unwanted adverse effects. The poor
      solubility is a problem for developing injectable solution dosage forms. Because
      of its poor skin permeability, it is difficult to obtain an effective therapeutic
      concentration from topical preparations. This review aims to give a brief insight
      into the status of ibuprofen dosage forms and their limitations,
      particle/crystallization technologies for improving formulation strategies as
      well as suggesting its incorporation into the pulmonary drug delivery systems for
      achieving better therapeutic action at low dose.

PMID- 29022773
TI  - Native paraneurial tissue and paraneurial adhesions alter nerve strain
      distribution in rat sciatic nerves.
AB  - Paraneurial adhesions have been implicated in the pathological progression of
      entrapment neuropathies. Surgical decompression of adhesions is often performed,
      with the intent of restoring nerve kinematics. The normal counterpart of
      adhesions, native paraneurium, is also thought to influence nerve deformation and
      mobility. However, influences of native or abnormal paraneurial structures on
      nerve kinematics have not been investigated. We measured regional strains in rat
      sciatic nerves before and immediately after decompression of native paraneurial
      tissue, and before and after decompression of abnormal paraneurial adhesions,
      which formed within 6 weeks of the initial decompression. Strain was
      significantly higher in the distal-femoral than in the mid-femoral region of the
      nerve before either decompression. Decompression of native and abnormal
      paraneurial tissue removed this regional strain difference. Paraneurial tissues
      appear to play a major role in distributing peripheral nerve strain. Normal nerve
      strain distributions may be reconstituted following decompression, even in the
      presence of paraneurial adhesions.

PMID- 29022774
TI  - The management of chronic non-arthritic scapholunate dissociation: a systematic
      review.
AB  - : A systematic review was conducted to identify the best management for chronic
      scapholunate dissociation. EMBASE, MEDLINE, and CENTRAL were searched from 1965
      2016. A narrative synthesis was performed. One thousand, one hundred and ninety
      one citations were identified, of which 17 had final analysis. In all
      interventions, the pain score at 2 years reduced from 6.0 to 2.8 with similar
      effect from capsulodesis and tenodesis techniques. Overall there was an 18% loss
      of flexion arc. Radial to ulnar arc improved in capsulodesis (+19%; n = 45) and
      worsened in tenodesis (-6%; n = 45). Grip strength was better in capsulodesis
      (+31%; n = 64 versus + 11%; n = 56). There was insufficient evidence to link
      radiological outcome with clinical outcome. Rates of complications (20%) and CRPS
      (3.8%) were high, with implications for patient consent. Due to heterogeneity in
      data collection, the lack of comparative studies and short-term follow-up, no
      conclusion regarding the superiority of a single technique was possible. Longer
      term comparative studies are required, as are natural history studies. A minimum
      data set has been advised. LEVEL OF EVIDENCE: II.

PMID- 29022775
TI  - Arthroscopic versus open excision of dorsal ganglion cysts: a systematic review.
AB  - : We conducted a systematic review comparing recurrence and complication rate
      following open versus arthroscopic excision of ganglion cysts. Sixteen full-text
      articles were included. The pooled recurrence rate of open excision was 20%
      (range: 5.6-40.7%) with Q value of 27 and I2 of 82%. The pooled recurrence rate
      of arthroscopic excision was 9% (range: 0-17%) with Q value of 10 and I2 of 2%.
      Eleven of 16 studies were low quality or had a high risk of bias; however,
      excluding low quality studies or those with high risk of bias produced similar
      recurrence rates in arthroscopic and open excision (7.9% versus 9.8%). For the
      subset of studies with complete reporting of complications, rates were similar in
      open and arthroscopic excision (6% versus 4%). Our review suggests that
      arthroscopic and open approaches have comparable outcome profiles. Nevertheless,
      standardized study methods with adequate powering are required to collect high
      quality data, allowing for greater confidence in conclusions regarding these two
      approaches for existing ganglion cysts. LEVEL OF EVIDENCE: II.

PMID- 29022776
TI  - Classification of synpolydactyly: experience in 10 children.

PMID- 29022777
TI  - Feasibility of modified Dixon MRI techniques for hepatic fat quantification in
      hepatic disorders: validation with MRS and histology.
AB  - OBJECTIVE: To assess the feasibility of proton density fat fraction (PDFF) MRI
      for estimating hepatic fat fraction with magnetic resonance spectroscopy (MRS)
      and histology as references and to investigate intrahepatic fat distribution and
      variability. METHODS: Between November 2014 and September 2015, 85 adults (48
      males, 47 females) who underwent MRI-PDFF (n = 139), MRS-PDFF (n = 49) and liver
      biopsy (n = 29) were enrolled in this study. Data were compared using linear
      regression. MRI-PDFF and standard deviations (variability) and differences
      between maximum and minimum PDFF (PDFF range) for whole liver, the lobes, and
      segment levels were calculated for each subject. RESULTS: Whole-liver MRI-PDFF
      showed good correlation with MRS-PDFF (r = 0.961) and histologic degree of
      hepatic steatosis (sigma = 0.809). Hepatic fat fraction is different between
      lobes and segments. Mean PDFF and mean PDFF range of the right lobe were higher
      than for the left lobe, whereas variability in the right lobe was lower than in
      the left lobe. CONCLUSION: MRI-PDFF is an accurate non-invasive method for
      quantifying hepatic fat for various hepatic disorders, and may be preferable for
      measuring fat fraction in the right liver for more precise values in longitudinal
      monitoring, while avoiding FF measurement in the left liver. Advances in
      knowledge: MRI-PDFF provides a non-invasive and accurate quantification of
      hepatic steatosis in various hepatic disorders. It would be preferable to measure
      FF in the right liver than in the left liver.

PMID- 29022778
TI  - The variability in Oxford hip and knee scores in the preoperative period: is
      there an ideal time to score?
AB  - Background All NHS-funded providers are required to collect and report patient
      reported outcome measures for hip and knee arthroplasty. Although there are
      established guidelines for timing such measures following arthroplasty, there are
      no specific time-points for collection in the preoperative period. The primary
      aim of this study was to identify whether there was a significant amount of
      variability in the Oxford hip and knee scores prior to surgical intervention when
      completed in the outpatient clinic at the time of listing for arthroplasty or
      when completed at the preoperative assessment clinic. Methods A prospective
      cohort study of patients listed for primary hip or knee arthroplasty was
      conducted. Patients were asked to fill in a preoperative Oxford score in the
      outpatient clinic at the time of listing. They were then invited to fill in the
      official outcome measures questionnaire at the preoperative assessment clinic.
      The postoperative Oxford score was then completed when the patient was seen again
      at their postoperative follow up in clinic. Results Of the total of 109 patients
      included in this study period, there were 18 (17%) who had a worse score of 4 or
      more points difference and 43 (39.4%) who had an improvement of 4 or more points
      difference when the scores were compared between time of listing at the
      outpatient and at the preoperative assessment clinic. There was a statistically
      significant difference (P = 0.0054) in the mean Oxford scores. Conclusions The
      results of our study suggest that there should be standardisation of timing for
      completing the preoperative patient-reported outcome measures.

PMID- 29022779
TI  - Short-term surgical outcomes and patient quality of life between robotic and
      laparoscopic extralevator abdominoperineal excision for adenocarcinoma of the
      rectum.
AB  - Introduction Some studies advocate a laparoscopic extralevator abdominoperineal
      excision (l-ELAPE) approach for low rectal cancer. The da VinciTM robot (r-ELAPE)
      technique has potential to overcome some limitations of l-ELAPE, such as
      reduction of the learning curve and more precise tissue handling. It is unknown
      whether this approach results in improved surgical or quality of life outcomes
      compared with l-ELAPE. This study aimed to address this issue. Methods
      Consecutive patients having undergone either robotic or laparoscopic ELAPE for
      adenocarcinoma were studied. All operations were performed by two surgeons
      experienced in laparoscopic and recently introduced robotic surgery. Surgical
      outcomes were determined by postoperative histology and short-term complications.
      Quality of life was prospectively assessed using the European Organisation for
      Research and Treatment of Cancer QLC-CR30 and QLC-CR29 questionnaires. Results A
      total of 22 patients (11 r-ELAPE) with a median follow-up of 13 months (8 months
      robotic; 22 months laparoscopic) were studied. The groups were similarly matched
      for age, gender, American Society of Anesthesiologists status, preoperative
      chemoradiotherapy and tumour height. All had R0 resection. There was no
      significant difference in short-term surgical outcomes between groups. There was
      no significant difference in mean global health scores between the two groups (74
      +/- 14 r-ELAPE vs. 73 +/- 10 l-ELAPE). The r-ELAPE group had a lower mean
      impotence score compared with the I-ELAPE group (55.5 +/- 40 vs. 72.2 +/- 44),
      although this was not statistically significant. Conclusions The newly introduced
      r-ELAPE was non-inferior to l-ELAPE in either patient quality of life or surgical
      outcomes. Robotic surgery could be particularly beneficial in the technically
      challenging area of low rectal cancer surgery with a shorter learning curve than
      laparoscopy.

PMID- 29022780
TI  - Primary urethral reconstruction results in penile fracture.
AB  - Objective This study assessed primary urethral reconstruction results in patients
      with a penile fracture. Materials and methods Between January 2005 and April
      2016, patients who underwent primary urethral reconstruction due to penile
      fracture were called for a follow-up. Epidemiological and clinical presentation
      data and operative findings were reviewed retrospectively. Partial urethral
      lesions were primarily treated with interrupted absorbable sutures over urethral
      catheter. In cases of complete urethral lesion, tension-free end-to-end
      anastomosis was performed. From the third month after surgery, all patients were
      interviewed using the International Prostate Symptom Score questionnaire and
      uroflowmetry. Retrograde urethrocystography was used in patients with urinary
      symptoms or altered uroflowmetry to rule out or confirm urethral stenosis.
      Results Of 175 patients with penile fractures, 27 (15.4%) had associated urethral
      injury. All patients were diagnosed with penile fracture by means of clinical
      history and physical examination. No subsequent examinations were conducted. Ages
      varied from 30 years to 58 years old (mean 39.2 years). All fractures resulted
      from sexual activity. Reported sexual positions were 'doggy style' position in
      eight cases (61.5%) and with the 'man on top' in five cases (38.4%). Ten patients
      (76.9%) experienced haematuria, ten (76.9%) had urethral bleeding and four
      (30.7%) suffered urinary retention. Unilateral and bilateral injury of the corpus
      cavernosum was observed in four (30.7%) and nine (69.2%) patients, respectively;
      partial injury was found in nine cases (69.3%) and complete urethral injury was
      noticed in four cases (30.7%). All cases of complete urethral injury were
      associated with bilateral lesion of the corpus cavernosum. Six patients who had
      uroflowmetry with maximum urinary flow rate below 15 ml/s and/or had IPSS above 7
      underwent retrograde urethrocystogram, and this was normal in all cases,
      excluding the possibility of urethral stenosis. Two patients (15.3%) experienced
      surgical postoperative complications represented by an urethrocutaneous fistula
      and a subcutaneous abscess adjacent to the end-to-end anastomosis area.
      Conclusions Penile fracture is a rare urological emergency, especially when it is
      associated with a urethral lesion. This must be suspected when the clinical
      picture is suggestive or in cases of high-energy trauma, especially in bilateral
      lesions of the corpus cavernosum. Complementary imaging methods are not needed in
      these cases and immediate exploration should not be delayed. Primary
      urethroplasty produces satisfactory results with low complication levels.
      Nonetheless, prospective studies with larger samples should be conducted.

PMID- 29022781
TI  - Near-infrared autofluorescence imaging to detect parathyroid glands in thyroid
      surgery.
AB  - Objective To identify and save parathyroid glands during thyroidectomy by
      displaying their autofluorescence. Methods Autofluorescence imaging was carried
      out during thyroidectomy with and without central lymph node dissection. After
      visual recognition by the surgeon, the parathyroid glands and the surrounding
      tissue were exposed to near-infrared light with a wavelength of 690-770 nm using
      a modified Karl Storz near infrared/indocyanine green endoscopic system.
      Parathyroid tissue was expected to show near infrared autofluorescence at 820 nm,
      captured in the blue channel of the camera. Results We investigated 41
      parathyroid glands from 20 patients; 37 glands were identified correctly based on
      near-infrared autofluorescence. Neither lymph nodes nor thyroid revealed
      substantial autofluorescence and nor did adipose tissue. Conclusions Parathyroid
      tissue is characterised by showing autofluorescence in the near-infrared
      spectrum. This effect can be used to identify and preserve parathyroid glands
      during thyroidectomy.

PMID- 29022783
TI  - Current predictive models do not accurately differentiate between single and
      multi gland disease in primary hyperparathyroidism: a retrospective cohort study
      of two endocrine surgery units.
AB  - Background Minimally invasive parathyroidectomy (MIP) for primary
      hyperparathyroidism is dependent upon accurate prediction of single-gland disease
      on the basis of preoperative imaging and biochemistry. The aims of this study
      were to validate currently available predictive models of single-gland disease in
      two UK cohorts and to determine if these models can facilitate MIP. Methods This
      is a retrospectively cohort study of 624 patients who underwent parathyroidectomy
      for primary hyperparathyroidism in two centres between July 2008 and December
      2013. Two recognised models: CaPTHUS (preoperative calcium, parathyroid hormone,
      ultrasound, sestamibi, concordance imaging) and Wisconsin Index (preoperative
      calcium, parathyroid hormone) were validated for their ability to predict single
      gland disease. Results The rates of single- and multi-gland disease were 491
      (79.6%) and 126 (20.2%), respectively. Cure rates in centres 1 and 2 were 93.2%
      and 93.8%, respectively (P = 0.789). The positive predictive value (PPV) of
      CaPTHUS score . 3 in predicting single-gland disease was 84.6%, compared with
      100% in the original report. CaPTHUS . 4 and 5 had a PPV of 85.1 and 87.1,
      respectively. There were no differences in Wisconsin Index (WIN) between patients
      with single- and multi-gland (P = 0.573). A WIN greater than 1600 and weight of
      excised gland greater than 1 g had a positive predictive value of 86.7% for
      single-gland disease. Conclusions The use of CaPTHUS and WIN indices without
      intraoperative adjuncts (such as IOPTH) had the potential to result in failure to
      cure in up to 15% (CaPTHUS) and 13% (WIN) of patients treated by MIP targeting a
      single enlarged gland.

PMID- 29022784
TI  - The exploding tumour on breast magnetic resonance imaging: an infected skin
      comedo.
AB  - A 61-year-old woman with a histologically proven invasive lobular carcinoma
      entered a clinical trial, which involved repeat magnetic resonance imaging (MRI).
      The protocol of the repeated MRI described a T4 breast cancer with involvement of
      the skin (Fig 1). There were only 17 days between the first and second MRI and
      during this short time it appeared that there had been rapid disease progression.
      On the initial MRI, a skin comedo could be seen in the left breast close to the
      tumour. The patient had squeezed the skin comedo, which had become infected. The
      second MRI captured the infected skin comedo, which had the appearance of an
      extensive breast cancer with skin involvement. The patient could be mismanaged if
      the clinician does not correlate the clinical findings with the radiological
      findings.

PMID- 29022782
TI  - Intramuscular compared with subcutaneous transposition for surgery in cubital
      tunnel syndrome.
AB  - Background There is no consensus on the most effective surgical technique in the
      treatment of cubital tunnel syndrome. Anterior subcutaneous transposition (AST)
      and anterior intramuscular transposition (AIT) are common surgical treatments in
      this regard. The aim of this study was to compare the clinical outcomes of these
      two surgeries for cubital tunnel syndrome. Methods In a retrospective study, we
      compared surgical outcomes (pain, sensation, motor recovery, atrophy, and total
      satisfaction) in 40 patients undergoing AIT and 43 undergoing AST of the ulnar
      nerve. Results The patients undergoing AIT showed a significant improvement in
      all the outcomes after the surgery (P = 0); however, those undergoing AST only
      experienced an improvement in pain and sensation after the surgery (P = 0).
      Comparing the two surgeries, we found that there was a high total satisfaction
      with AIT compared with AST (P = 0). When we independently compared each outcome
      in the two groups, we found that the muscle force recovery was significantly
      improved in the AIT group compared with the AST group (P = 0). Conclusions AIT is
      preferable to AST for the surgical treatment of cubital tunnel syndrome. In
      particular, AIT achieves a better motor recovery of the ulnar nerve compared with
      AST.

PMID- 29022785
TI  - The management of pretibial lacerations.
AB  - Introduction Pretibial lacerations are common injuries, often presenting in the
      elderly and infirm. Unclear management pathways often result in inappropriate
      care. We identify patient demographics, morbidity risk factors, injury severity
      and management options. Materials and methods This retrospective study involved
      analysing databases and hardcopy notes for patients admitted with pretibial
      lacerations to Addenbrooke's Hospital, January to December 2012. Microsoft Excel
      and Fishers exact test were used to analyse the data with a P-value of less than
      0.05 representative of statistical significance. Information on patient
      demographics, site of lesion, preoperative symptoms, management, operative
      details and clinical outcomes were collected. Results A total of 36 patients were
      identified; the mean age was 79 years (+/- 16 years, 1 standard deviation) with a
      three to two female to male preponderance; 57% of injuries were caused by
      mechanical fall, 33% traumatic blunt impact and 7% road traffic accidents.
      American Society of Anesthesiologists physical status classification was 43%
      level III, 40% II, 9% I and 9% IV. Dunkin classification of severity was 33%
      grade III, 30% grade I, 24% grade IV and 12% grade II. Median inpatient duration
      was 11 days for surgically managed compared with 15 days for conservatively
      managed patients. Discussion Pretibial lacerations tend to affect the elderly.
      Management is compounded by polypharmacy and comorbidities. If inadequately
      managed, such injuries can adopt characteristics of chronic wounds, with lengthy
      inpatient stays. Surgical intervention may be appropriate where injuries are
      severe and the patient stable enough for theatre. Conclusions We believe that
      surgical management with autologous tissue repair, with minimal delay between
      presentation and theatre, is warranted for extensive injuries wherever possible,
      with conservative management used for predominantly less extensive pretibial
      lacerations.

PMID- 29022786
TI  - Necrotising fasciitis of the left leg caused by perforated caecal adenocarcinoma.
AB  - An 82-year-old man presented with abdominal pain and a painful and swollen left
      thigh. On examination there was oedema, tenderness and crepitus with skin
      discoloration of the left thigh. Computed tomography showed retroperitoneal
      perforation of the caecum and necrotising fasciitis of the left thigh. A right
      hemicolectomy and repeated fasciotomies of the left thigh with debridement of
      necrotic tissue were performed but the patient died of multi-organ failure.
      Histology showed a pT4aN2c caecal adenocarcinoma. This is a unique presentation
      of a retroperitoneal caecal perforation and acts as a reminder that unexplained
      severe fasciitis of the thigh may be caused by an intra-abdominal pathology.

PMID- 29022787
TI  - Does a missed obstetric anal sphincter injury at time of delivery affect short
      term functional outcome?
AB  - Introduction This study aimed to ascertain whether missed obstetric anal
      sphincter injury at delivery had worse functional and quality of life outcomes
      than primary repair immediately following delivery. Materials and methods Two to
      one propensity matching was undertaken of patients presenting to a tertiary
      pelvic floor unit with ultrasound evidence of missed obstetric anal sphincter
      injury within 24 months of delivery with patients who underwent primary repair at
      the time of delivery by parity, grade of injury and time to assessment. Outcomes
      compared included Birmingham Bowel, Bladder and Urinary Symptom Questionnaire
      (BBUSQ), Wexner Incontinence Score, Short Form-36, Pelvic Organ Prolapse/Urinary
      Incontinence Sexual Questionnaire and anorectal physiology results. Results
      Thirty-two missed anal sphincter injuries were matched two to one with sixty-two
      patients who underwent primary repair of an anal sphincter defect. Mean time to
      follow-up was 9.31 +/- 6.79 months. Patients with a missed anal sphincter injury
      had suffered more incontinence, as seen in higher the Birmingham Bowel, Bladder
      and Urinary Symptom Questionnaire (BBUSQ; 30.56% +/- 14.41% vs. 19.75% +/-
      15.65%, P = 0.002) and Wexner scores (6.00 +/- 3.76 vs. 3.67 +/- 4.06, P =
      0.009). They also had a worse BBUSQ urinary domain score (28.25% +/- 14.9% vs.
      17.01 +/- 13.87%, P = 0.001) and worse physical functioning as measured by the
      Short Form-36 questionnaire (P = 0.045). There were no differences in other
      outcomes compared, including anorectal physiology and sexual function. Discussion
      In the short-term, patients with a missed obstetric anal sphincter injury had
      significantly worse faecal incontinence and urinary function scores, however
      quality of life and sexual function were largely comparable between groups.
      Conclusions Longer-term follow-up is needed to assess the effects of missed
      obstetric anal sphincter injury over time.

PMID- 29022788
TI  - Developing a simplified clinical prediction score for mortality in patients with
      cerebral gunshot wounds: The Maritzburg Score.
AB  - Introduction Cerebral gunshot wounds are highly lethal and literature on the
      clinical scores for mortality prediction is limited. Materials and methods A
      retrospective study was undertaken over a 5-year period at the Pietermaritzburg
      Metropolitan Trauma Service in South Africa. A simplified clinical prediction
      score was developed based on clinical and/or physiological variables readily
      available in the resuscitation room. Results A total of 102 patients were
      included; 92% (94/102) were male and the mean age was 29 years; 22% (22/102) died
      during the admission. The presence of visible brain matter (odds ratio 12.4, P =
      0.003) and motor score less than 5 (odds ratio 89.6, P  < 0.001) allows the
      prediction success of 92% (sensitivity 73% and specificity 98%). The area under
      the receiver operating characteristic curve was 94% (95% confidence interval 88
      100%, P  < 0.001). Conclusions The presence of visible brain matter, together
      with a motor score of less than 5, allows accurate identification of non
      survivors of cerebral gunshot wounds. Further study is required to validate this
      score.

PMID- 29022789
TI  - The impact of mechanism on the management and outcome of penetrating colonic
      trauma.
AB  - Introduction In light of continuing controversy surrounding the management of
      penetrating colonic injuries, we set out to compare the outcome of penetrating
      colonic trauma according to whether the mechanism of injury was a stab wound or a
      gunshot wound. Methods Our trauma registry was interrogated for the 5-year period
      from January 2012 to December 2016. All patients over the age of 18 years with
      penetrating trauma (stab or gunshot) and with intraoperatively proven colonic
      injury were reviewed. Details of the colonic and concurrent abdominal injuries
      were recorded, together with the operative management strategy. In-hospital
      morbidities were divided into colon-related and non-colon related morbidities.
      The length of hospital stay and mortality were recorded. Direct comparison was
      made between patients with stab wounds and gunshot wounds to the colon. Results
      During the 5-year study period, 257 patients sustained a colonic injury secondary
      to penetrating trauma; 95% (244/257) were male and the mean age was 30 years. A
      total of 113 (44%) sustained a gunshot wound and the remaining 56% (144/257)
      sustained a stab wound. Some 88% (226/257) of all patients sustained a single
      colonic injury, while 12% (31/257) sustained more than one colonic injury. A
      total of 294 colonic injuries were found at laparotomy. Multiple colonic injuries
      were less commonly encountered in stab wounds (6%, 9/144 vs. 19%, 22/113, P <
      0.001). Primary repair was more commonly performed for stab wounds compared with
      gunshot wounds (118/144 vs. 59/113, P < 0.001). Patients with gunshot wounds were
      more likely to need admission to intensive care, more likely to experience
      anastomotic failure, and had higher mortality. Conclusions It would appear that
      colonic stab wounds and colonic gunshot wounds are different in terms of severity
      of the injury and in terms of outcome. While primary repair is almost always
      applicable to the management of colonic stab wounds, the same cannot be said for
      colonic gunshot wounds. The management of colonic gunshot wounds should be
      examined separately from that of stab wounds.

PMID- 29022790
TI  - Accelerated discharge within 72 hours of colorectal cancer resection using simple
      discharge criteria.
AB  - Introduction Short hospital stays and accelerated discharge within 72 hours
      following colorectal cancer resections have not been widely achieved. Series
      reporting on accelerated discharge involve heterogeneous patient populations and
      exclude important groups. Strict adherence to some discharge requirements may
      lead to delays in discharge. The aim of this study was to evaluate the safety and
      feasibility of accelerated discharge within 72 hours of all elective colorectal
      cancer resections using simple discharge criteria. Methods Elective colorectal
      cancer resections performed between August 2009 and December 2015 by a single
      surgeon were reviewed. Perioperative care was based on an enhanced recovery
      programme. A set of simplified discharge criteria were used. Outcomes including
      postoperative complications, readmissions and reoperations were compared between
      patients discharged within 72 hours and those with a longer postoperative stay.
      Results Overall, 256 colorectal cancer resections (90% laparoscopic) were
      performed. The mean patient age was 70.8 years. The median length of stay was 3
      days. Fifty-eight per cent of all patients and sixty-three per cent of patients
      undergoing laparoscopic surgery were discharged within 72 hours. Accelerated
      discharge was not associated with adverse outcomes compared with delayed
      discharge. Patients discharged within 72 hours had significantly fewer
      postoperative complications, readmissions and reoperations. Open surgery and
      stoma formation were associated with discharge after 72 hours but not age, co
      morbidities, neoadjuvant chemoradiation or surgical procedure. Conclusions
      Accelerated discharge within 72 hours of elective colorectal resection for cancer
      is safely achievable for the majority of patients without compromising short-term
      outcomes.

PMID- 29022791
TI  - X-Bolt unforeseen placement complication: case report.
AB  - With the introduction of the World Hip Trauma Evaluation Four clinical trial,
      fixation of pertrochanteric neck of femur fractures is becoming a hot topic. In
      this trial, the novel X-Bolt expanding bolt implant is being compared with the
      current gold standard of a sliding hip screw. We present a previously undescribed
      complication when inserting the bolt into the femoral head, where the expandable
      wings penetrate the femoral neck due to misplacement of the bone crusher or the X
      Bolt prosthesis. This unforeseen complication required the introduction of
      several additional corrective intraoperative steps.

PMID- 29022792
TI  - A case of massive porocarcinoma.
AB  - A 53-year-old Cambodian woman presented with nodular masses on the right arm
      suggestive of a sarcoma-type malignancy. The masses were excised and identified
      as multiple benign eccrine poromas. The patient re-presented after two years with
      large relapsed tumours and axillary lymph node involvement. A forequarter
      amputation was undertaken. Histology confirmed the diagnosis of a porocarcinoma,
      which was likely to be due to malignant transformation of the original poromas.
      The size and multiplicity of the tumours represents a highly unusual presentation
      of these rare eccrine neoplasms.

PMID- 29022793
TI  - Intralesional excision with topical intralesional cryotherapy improves the
      treatment of keloid scarring in a paediatric patient.
AB  - Recurrent keloid scarring has a significant impact on quality of life. Management
      is complex, particularly for scars resistant to conventional treatments and in
      paediatric cases where radiotherapy is not a suitable adjunct to surgical
      excision. We present the case of a nine-year-old African Caribbean girl with
      multiple large and recurrent keloid scars on both ears and bilateral
      sensorineural deafness. Following repeated intralesional excisions,
      corticosteroid and botulinum toxin injections, she continued to experience rapid
      recurrence of her keloids, worsening pain and pruritus. She was no longer able to
      wear her hearing aids because of the large size of the keloids. We employed a
      novel technique using topical intralesional cryotherapy, applying liquid nitrogen
      intraoperatively to the inside of the skin flaps immediately post-intralesional
      keloid excision and before wound closure. At 26-month follow-up a good aesthetic
      and symptomatic result was achieved, with minimal hypopigmentation, significantly
      reduced scar volume and significantly slowed recurrence. We discuss this case and
      review the current literature on the use of topical intralesional cryotherapy for
      keloid scarring.

PMID- 29022794
TI  - An assessment of pelvic binder placement at a UK major trauma centre.
AB  - Introduction Pelvic binders are used to reduce the haemorrhage associated with
      pelvic ring injuries. Application at the level of the greater trochanters is
      required. We assessed the frequency of their use in patients with pelvic ring
      injuries and their positioning in patients presenting to a single major trauma
      centre. Methods A retrospective review of our trauma database was performed to
      randomly select 1000 patients for study from April 2012 to December 2016.
      Patients with a pelvic binder or a pelvic ring injury defined by the Young and
      Burgess classification were included. Computed tomography was used to identify
      and measure pelvic binder placement. Results 140 patients were identified:
      110/140 had a binder placed. Of the total, 54 (49.1%) patients had satisfactory
      placement and 56 (50.9%) had unsatisfactory placement; 30/67 (44.8%) patients
      with a pelvic ring injury had no binder applied, of whom 6 (20%) had an unstable
      injury; 9/67 patients died. Discussion This is the first study assessing pelvic
      binder placement in patients at a UK major trauma centre. Unsatisfactory
      positioning of the pelvic binder is a common problem and it was not used in a
      large proportion of patients with pelvic ring injuries. This demonstrates that
      there is a need for continuing education for teams dealing with major trauma.

PMID- 29022795
TI  - Local recurrence after 'standard' abdominoperineal resection: do we really need
      ELAPE?
AB  - Introduction Low rectal cancers requiring abdominoperineal resection tend to have
      a worse prognosis than higher tumours, which may be treated by anterior
      resection. One of the reasons for this may be inadequate local surgery, in
      particular the narrow waist of the resection specimen of a standard
      abdominoperineal resection may be associated with a high positive circumferential
      resection margin. The extralevator abdominoperineal excision (ELAPE) aims to
      improve the R0 resection rate but carries significant morbidity. We examined our
      own results of standard abdominoperineal resection to assess the need for a
      change of policy. Methods We operformed a retrospective analysis of consecutive
      standard abdominoperineal resections for rectal cancer in a single centre from
      June 2002 to December 2011. Results A total of 102 patients underwent standard
      abdominoperineal resection with curative intent; 19 had no preoperative
      treatment, 42 had short course radiotherapy, 9 had long course radiotherapy and
      32 had neoadjuvant chemotherapy followed by long course chemoradiotherapy. In
      17/102(16.6%), there was a positive circumferential resection margin. Over a
      median follow up of 32 months, 20 patients developed recurrence of any type.
      Local recurrence occurred in five patients (two of which also had distant
      recurrence), of whom two had a positive circumferential resection margin (P =
      0.10). Actuarial two-year local only recurrence was 3.4% and any recurrence was
      17.7%. Overall five-year cancer specific survival was 77%. Conclusions In this
      series we found low rates of local recurrence after standard abdominoperineal
      resection even with a circumferential margin rate positivity of 16.6%.Performing
      an ELAPE in selected cases may improve these results further but is not
      necessarily required for all patients.

PMID- 29022796
TI  - Aural exostoses (surfer's ear) provide vital fossil evidence of an aquatic phase
      in Man's early evolution.
AB  - For over a century, otolaryngologists have recognised the condition of aural
      exostoses, but their significance and aetiology remains obscure, although they
      tend to be associated with frequent swimming and cold water immersion of the
      auditory canal. The fact that this condition is usually bilateral is predictable
      since both ears are immersed in water. However, why do exostoses only grow in
      swimmers and why do they grow in the deep bony meatus at two or three constant
      sites? Furthermore, from an evolutionary point of view, what is or was the
      purpose and function of these rather incongruous protrusions? In recent decades,
      paleoanthropological evidence has challenged ideas about early hominid evolution.
      In 1992 the senior author suggested that aural exostoses were evolved in early
      hominid Man for protection of the delicate tympanic membrane during swimming and
      diving by narrowing the ear canal in a similar fashion to other semiaquatic
      species. We now provide evidence for this theory and propose an aetiological
      explanation for the formation of exostoses.

PMID- 29022797
TI  - Surgery performed by supervised registrars does not adversely affect medium-term
      functional outcomes after total knee replacement.
AB  - Introduction Although total knee arthroplasty (TKA) is an index procedure for
      orthopaedic registrars, there is a lack of published research as to the effects
      of surgery when performed by supervised trainees. The aim of this study was to
      compare functional outcomes up to five years after primary TKA performed by
      consultants and trainee surgeons. Methods A retrospective analysis was conducted
      of prospectively collected data for 609 consecutive patients (339 female, 270
      male) undergoing TKA. Patients were assessed preoperatively as well as at 18
      months, three years and five years postoperatively, and American Knee Society
      objective knee and functional scores (AKSK and AKSF) were recorded. Results
      Surgery was performed by a consultant in 465 cases and a supervised trainee in
      144 cases. There were no significant differences between the two groups in
      preoperative patient characteristics, operative time (p=0.15), transfusion rates
      (p=0.84), length of stay (p=0.98), manipulation under anaesthesia (p=0.69), or
      mortality rates at one year (p=0.73) or five years (p=0.81). Postoperatively, the
      median magnitude of improvement in AKSK (48 points for consultant group vs 45
      points for trainee group, p=0.74) and in AKSF (both groups 15, p=0.995) was
      similar between the groups. AKSK and AKSF scores were similar at all timepoints
      up to five years following surgery, and there was no difference in the median
      range of motion (both groups 100 degrees , IQR: 18 degrees ) at five years
      (p=0.43). Conclusions TKA performed by supervised registrars gives functional
      outcomes that are equivalent to consultant performed TKA, without affecting
      postoperative range of movement, or increasing operative time, length of stay or
      transfusion rates. Rates of postoperative MUA and mortality are also comparable.

PMID- 29022798
TI  - A rare case of simultaneous pneumoperitoneum and pneumomediastinum with a review
      of the literature.
AB  - Simultaneous pneumoperitoneum and pneumomediastinum is a rare clinical
      occurrence. It has been reported in the literature as a complication of various
      medical and dental procedures. To our knowledge, we present the first case of a
      non-iatrogenic and traumatic simultaneous pneumoperitoneum and pneumomediastinum
      in a previously independent 91-year-old man who presented to hospital with back
      and chest wall pain following mechanical fall from standing. A new radiological
      diagnosis of diverticular disease with possible perforation was made following
      admission. Despite appropriate management and supportive measures, the patient
      died 12 days after admission from a kidney injury.

PMID- 29022799
TI  - Perineal Richter's herniation following proctectomy.
AB  - In a Richter's hernia, only part of the anti-mesenteric border of the bowel is
      incarcerated within the underlying defect. We report three cases presenting
      between 18 days and 11 years following proctectomy. As all patients had
      functioning stomas a high index of suspicion is necessary to avoid a delay in
      diagnosis.

PMID- 29022800
TI  - Staple line integrity test in sleeve gastrectomy.

PMID- 29022801
TI  - Reduced port number in laparoscopic cholecystectomy for acute cholecystitis
      following percutaneous transhepatic gallbladder drainage.

PMID- 29022803
TI  - Assessing the amount of distraction needed for expandable anterior column cages
      in the cervical spine.

PMID- 29022802
TI  - Endoscopic-assisted local intralesional curettage and excision of intraosseous
      lesions in the talus.

PMID- 29022804
TI  - Air as contrast media for hip arthrogram.

PMID- 29022805
TI  - How to remove a ring using an oxygen mask.

PMID- 29022806
TI  - Single-incision distal biceps tendon repair using spinal retractors to achieve
      optimum exposure.

PMID- 29022807
TI  - Surgery for popliteal artery entrapment syndrome: use of an intraoperative tibial
      nerve stimulator and duplex ultrasound.

PMID- 29022808
TI  - A simple endoscopic method for removal of a knotted urethral catheter.

PMID- 29022809
TI  - Use of sponge heel boots as a temporary splint for paediatric elbow supracondylar
      fractures.

PMID- 29022810
TI  - The 'egg topping' technique for bone graft harvesting in hip arthroplasty.

PMID- 29022811
TI  - The inferior dermal flap technique for trans male chest contouring.

PMID- 29022812
TI  - The 'hand of rock' to assess upper limb peripheral neurological status in
      children.

PMID- 29022813
TI  - Real time ultrasound guided insertion of Veress needle in obese patients.

PMID- 29022814
TI  - A porcine model for teaching laparoscopic appendicectomy.

PMID- 29022815
TI  - Reinforcement of sutures to close surgical incisions in frail skin.

PMID- 29022816
TI  - Increased safety of surgical glove application: the under/over method.

PMID- 29022818
TI  - A cheap, simple and sterile surgical bolster.

PMID- 29022817
TI  - Endourological management of misplaced urethral catheter after radical
      prostatectomy.

PMID- 29022819
TI  - Two uses of the Smillie knife in foot and ankle surgery.

PMID- 29022820
TI  - A simple method to find the proximal stump of the cut flexor pollicis longus
      tendon in the thenar zone.

PMID- 29022821
TI  - Using nylon tape to aid the formation of loop stomas.

PMID- 29022822
TI  - A late presentation of Loeys-Dietz syndrome associated with an aortic root
      aneurysm.
AB  - Loeys-Dietz syndrome (LDS) is characterised by a mutation in the transforming
      growth factor beta receptor, and is strongly associated with aortic aneurysms and
      rupture. Most cases of LDS present in the second decade of life, with the average
      life expectancy being 37 years. We report a case of suspected LDS (owing to
      significant family history of the disorder) that presented in the seventh decade
      of life. Our patient had aortic root dilation and was initially believed to have
      Marfan syndrome. However, subsequent tests were negative. On further
      investigation of her family history, it was revealed that she had a strong
      positive family history of aortic rupture and aneurysms associated with
      genetically confirmed atypical LDS. By reporting this case, we aim to highlight
      the importance of considering inherited connective tissue disorders when a
      patient presents with aortic aneurysms or dissections associated with a strong
      family history of aortic pathology.

PMID- 29022823
TI  - Impact of a medication reconciliation program on cardiac surgery patients.
AB  - Background Cardiac surgery patients are at high risk of medication errors.
      Resumption of home medications reduces the significance and number of medication
      errors. This could be achieved by implementing a medication reconciliation
      program. Patients and Methods Patients were eligible for inclusion in this
      prospective study if they were admitted, transferred, and/or discharged under
      cardiac surgery team care from September 2015 to March 2016. The primary outcome
      was the number and proportion of unintentional medication discrepancies.
      Secondary outcomes included the number of interventions to resolve discrepancies
      and their clinical significance, and the medication regimen complexity index and
      its correlation with discrepancies. Results There were 374 patients included and
      1000 encounters tracked. Four-hundred and seventy (47%) of the included
      encounters were for adult patients. Of the 260 medication discrepancies detected,
      181 (69.61%) were detected during admission. Discrepancies among adults were
      0.913, 0.307, and 0.176 on admission, transfer, and discharge, respectively. Two
      hundred (76.92%) of the interventions recommended by the pharmacy residents were
      accepted by the medical team, and the remaining were accepted with modifications,
      with no rejections. One-hundred and sixty-six (83%) of the accepted interventions
      were of high clinical significance. There was a significant correlation between
      the number of medication discrepancies and medication regimen complexity index on
      admission ( p < 0.0001, r = 0.34), transfer, and discharge. Conclusion
      Implementation of a medication reconciliation program in cardiac surgery units
      and its step-down units can be a powerful mean of identifying medication errors
      in post-cardiac surgery patients at admission and throughout the transition of
      care.

PMID- 29022824
TI  - Aortico-left ventricular tunnel: a rare congenital abnormality.

PMID- 29022825
TI  - MitraClip and mitral annuloplasty device as a bridge to transplantation.
AB  - A 42-year-old man with dilated cardiomyopathy and endstage heart failure was
      evaluated for heart transplantation. He received a MitraClip and Carillon
      annuloplasty device for functional mitral regurgitation as palliation for his
      heart failure. Subsequently, he underwent successful heart transplantation.

PMID- 29022826
TI  - Inflammatory myofibroblastic lung tumor with dysphagia in a 4-year-old child.
AB  - Inflammatory myofibroblastic tumors of the lung are rare in adults but common
      among pediatric lung tumors. A 4-year-old girl was evaluated for respiratory
      symptoms, dysphagia, and weight loss. Radiology revealed a right hilar mass that
      persisted despite antibiotic treatment. On exploration, a hilar mass involving
      the pulmonary vasculature, diaphragm and gastroesophageal junction was found.
      Aggressive surgical excision including a right pneumonectomy was performed.
      Histopathology confirmed an inflammatory myofibroblastic tumor with no features
      of malignancy. At the 2-year follow-up, the child was clinically stable with no
      recurrence. Dysphagia is a very rare presentation of such tumors.

PMID- 29022828
TI  - The Book Corner.

PMID- 29022827
TI  - Descending aortic aneurysm in Wiskott-Aldrich syndrome: options for repair.
AB  - We report open surgical repair of a previously stented descending thoracic
      aneurysm in a patient with Wiskott-Aldrich syndrome and a platelet count <10 *
      109.L-1. The same patient was described previously in a report of the first
      endovascular stent in this form of vasculitis. We describe the pre- and
      intraoperative management, and suggest a change in strategy in this setting.

PMID- 29022829
TI  - Migratory White Stork (Ciconia ciconia): A Potential Vector of the OXA-48
      Producing Escherichia coli ST38 Clone in Algeria.
AB  - The emergence of carbapenemase-producing Enterobacteriaceae is of great concern
      to public health worldwide. The aim of this study was to screen for the presence
      of carbapenemase-producing Enterobacteriaceae in white stork (Ciconia ciconia)
      migratory bird stools, and to investigate their molecular support on beta
      lactamase production. In March 2015, 32 fecal samples of white stork were
      collected in the Commune of El Madher Wilaya de Batna, in eastern Algeria.
      Samples were subjected to selective isolation of carbapenem-resistant
      Enterobacteriaceae. Representative colonies were screened phenotypically for
      carbapenemase production. Carbapenemase-producing isolates were subjected to
      antibiotic susceptibility testing and extended-spectrum beta-lactamase (ESBL)
      coproduction. beta-Lactamase determinants were searched for by PCR and
      sequencing. Three carbapenemase-producing Escherichia coli were obtained. Only
      one strain was positive for ESBL production. The OXA-48-type carbapenemase
      encoding gene was detected in all isolates. Screening for other beta-lactamase
      encoding genes showed that all isolates coexpress the blaTEM gene, whereas one of
      them additionally harbored the blaCTX-M-15 ESBL gene. Multilocus sequence typing
      results showed that two strains belonged to the sequence type 38. This work
      demonstrated for the first time that the migratory white stork can play an
      important role in the dissemination of OXA-48-producing E. coli as a potential
      reservoir and vector.

PMID- 29022830
TI  - Direct costs for nonsurgical management of Chronic Pancreatitis in a tertiary
      care teaching hospital.
AB  - BACKGROUND: Chronic pancreatitis (CP) is a leading cause of hospitalization among
      gastrointestinal diseases resulting in considerable financial burden to patients.
      However the direct costs for nonsurgical management in CP remains unexplored.
      METHODS: A cross sectional study was carried out (2011-14) in the Department of
      Gastroenterology, Kasturba Hospital, Manipal, India. Demographic and clinical
      data on laboratory investigations, interventions and follow up were obtained from
      the medical records department. Item costs were derived from the hospital
      electronic billing section. Cost was expressed as median annual cost per patient.
      RESULTS: 65 (male 48; 73.8%) patients were included. Their median age was 31
      (range 12-68) years. The annual median (IQR) total cost per patient was INR
      88,892 (70,550.5-116,004); [USD 1410(1119-1841); ? 1155(916-1507)], comprising of
      INR 61,089 (39,102.5-90,360.5) [USD 970 (621-1434); ? 793(508-1174)] for
      outpatient management and INR 32,450 (11,016-46,958) [USD 515 (175-745); ?421(143
      610)] for hospitalization. 69.5% of the treatment cost was attributed to
      outpatient treatment. Drugs contributed to 54%, hospitalization incurred 30.5%,
      investigations 12% and professional fees (3.5%) of the total cost. Pancreatic
      enzyme replacement therapy (PERT) cost contributed to three-quarters of drug
      therapy. Use of rabeprazole as against pantoprazole reduced the overall annual
      cost of therapy by 4%. CONCLUSIONS: This study depicts the first nonsurgical
      management of accrued direct costs associated with CP due to expensive
      medications. Due to the high cost for PERT, its usefulness needs proper
      validation by cost benefit analysis.

PMID- 29022831
TI  - Nuclear Magnetic Resonance-Assisted Metabolic Analysis of Plasma for Mild
      Gestational Diabetes Mellitus Patients.
AB  - AIMS: This study aimed at detecting the difference of metabolic profile in mild
      gestational diabetes mellitus (GDM) patients, and at identifying the correlation
      between the disturbed metabolites and insulin resistance pathway induced by the
      inflammation factors secreted by the placenta and adipocytes. MATERIALS AND
      METHODS: Blood samples were collected from 36 pregnant women diagnosed with mild
      GDM and 36 normal glucose-tolerant (NGT) pregnant women. Metabolic profiles were
      acquired by using proton nuclear magnetic resonance (1H-NMR) spectroscopy, and
      the data were analyzed by multivariate statistical data analysis. The messenger
      RNA (mRNA) expression of CX3CL1, CD14, and CD86 in placenta and omental adipose
      tissues was detected by quantitative real-time polymerase chain reaction.
      RESULTS: (1) Weight and body mass index in GDM group were remarkably higher at
      both pre-pregnancy and delivery than those in the NGT group. The levels of
      fasting blood glucose, insulin, and homeostasis model assessment-2 for insulin
      resistance in GDM group were also significantly higher than those in the NGT
      group. (2) The expression of mRNA of CD86 was significantly higher in placenta of
      GDM patients. However, the gene expression of CX3CL1 and CD86 in omental adipose
      tissues of GDM was markedly lower as compared with the control group. (3) The GDM
      group exhibited severely perturbed glucose metabolism, fatty acid metabolism,
      amino acid metabolism, and activated inflammatory response. CONCLUSIONS: The 1H
      NMR-based metabonomics approach together with biochemical assay and the mRNA
      expression analysis provided metabolic information about mild GDM, which
      indicated disturbed glucose metabolism, fatty acid metabolism, amino acid
      metabolism, and activated inflammatory response in mild GDM patients. This
      integrated study provides a new idea and methods to understand underlying
      mechanisms of mild GDM in clinics.

PMID- 29022832
TI  - Voltammetric detection of trifluralin in tap water, fruit juice, and vegetable
      extracts in the presence of surfactants.
AB  - This study describes a novel electrochemical method to determine the herbicide
      trifluralin in samples of water, fruit juice, and vegetable extracts in the
      presence of surfactants, using a glassy carbon electrode (GCE). In acidic media,
      trifluralin was irreversible on the glassy carbon electrode surface at -0.5 V vs.
      Ag/AgCl. Surfactant presence on the electrode-solution interface modified current
      intensities and shifted the reduction peak potential of trifluralin. Different
      types of surfactant and their concentrations were investigated. The anionic
      surfactant significantly enhanced the peak current intensity of trifluralin.
      Under optimal analytical conditions, an analytical curve was obtained in the
      concentration range of 0.48-32.20 uM. The limits of detection and quantification
      were estimated at 0.031 and 0.104 uM, respectively. The method was successfully
      applied to quantify trifluralin in samples of water, orange and tomato juice, and
      green pepper, carrot, and onion extracts, with recovery rates of 97.9-102.1%. The
      results were in good agreement with those obtained using high-performance liquid
      chromatography, indicating that the proposed electrochemical method can be
      employed to quantify trifluralin in various types foods, with sensitivity,
      specificity, selectivity and reproducibility.

PMID- 29022833
TI  - How to Initiate Dementia Care Networks? Processes, Barriers, and Facilitators
      During the Development Process of a Practice-Oriented Website Toolkit Out of
      Research Results.
AB  - BACKGROUND: Despite its high relevance, scientific evidence often fails to be
      disseminated into practice. Information websites can be a successful information
      dissemination tool, but very little is known about the processes involved in the
      interdisciplinary development of such websites. This article aims to demonstrate
      the processes, barriers, and facilitators during the development and publication
      of a practice-friendly information website grounded in scientifically based
      research findings about dementia care networks obtained by the DemNet-D study.
      METHOD: The qualitative data of this article are based on a work progress
      protocol and a recorded interview with the project's science journalist. The
      interview was transcribed, analyzed, and coded based on structured content
      analysis. Quantitative data were extracted to display the website usage rate.
      RESULTS: The results indicate that interdisciplinary teamwork is an essential
      factor for successful website development. Furthermore, the use of a formalized
      model can help to organize the development structure. To transform scientific
      content, a specialized expert in the field is needed. Continuous evaluations and
      marketing strategies are vital for the success of a website. The final website
      had a high access rate 1 month after launch. CONCLUSION: Crucial processes,
      barriers, and facilitators during the development of a practice-related
      information website about dementia care networks are presented and discussed.
      These findings can help people who aim to disseminate research findings to other
      practitioner-associated priority groups as well as public health-related groups.

PMID- 29022834
TI  - Phenolic-Protein Interactions: Effects on Food Properties and Health Benefits.
AB  - Phenolic-protein interactions (PPI), which naturally occur in most food systems,
      are being intentionally designed to enhance functional performance of phenolic
      compounds (PC). PPI have been primarily associated with changes related to
      sensorial, nutritional, and nutraceutical features of foods. Furthermore, these
      interactions affect properties such as astringency, protein digestibility,
      absorption, and bioavailability of antioxidants. Therefore, new product
      development should pay attention to these interactions and not only on the
      concentration of PC. PPI protect PC from degradation due to enzymatic attack or
      pH changes in the lumen of the intestinal tract. Due to PPI, PC are delivered to
      the colon where they are metabolized by the microbiota and generate an
      antioxidant environment. Interactions with proteins also may enhance the
      antiproliferative activity of PC in some specific tumor cell lines. In this
      review, the effects of PPI that affect both food properties and health benefits
      are discussed.

PMID- 29022836
TI  - 'Real-world' Australian experience of pomalidomide for relapsed and refractory
      myeloma.

PMID- 29022837
TI  - Critical Parameters for Particle-Based Pulmonary Delivery of Chemotherapeutics.
AB  - Targeted delivery of chemotherapeutics through the respiratory system is a
      potential approach to improve drug accumulation in the lung tumor, while
      decreasing their negative side effects. However, elimination by the pulmonary
      clearance mechanisms, including the mucociliary transport system, and ingestion
      by the alveolar macrophages, rapid absorption into the blood, enzymatic
      degradation, and low control over the deposition rate and location remain the
      main complications for achieving an effective pulmonary drug delivery. Therefore,
      particle-based delivery systems have emerged to minimize pulmonary clearance
      mechanisms, enhance drug therapeutic efficacy, and control the release behavior.
      A successful implementation of a particle-based delivery system requires
      understanding the influential parameters in terms of drug carrier, inhalation
      technology, and health status of the patient's respiratory system. This review
      aims at investigating the parameters that significantly drive the clinical
      outcomes of various particle-based pulmonary delivery systems. This should aid
      clinicians in appropriate selection of a delivery system according to their
      clinical setting. It will also guide researchers in addressing the remaining
      challenges that need to be overcome to enhance the efficiency of current
      pulmonary delivery systems for aerosols.

PMID- 29022835
TI  - Time for Multiple Extraction Methods in Proteomics? A Comparison of Three Protein
      Extraction Methods in the Eustigmatophyte Alga Microchloropsis gaditana CCMP526.
AB  - Proteomics is a crucial postgenomic biotechnology for functional and systems
      scale analyses in cell and integrative biology, not to mention clinical and
      precision medicine research. However, a fundamental requirement for an accurate
      examination of the protein complement of cells is an efficient method for
      extracting the proteins. This study reports on the evaluation of three protein
      extraction methods: trichloroacetic acid (TCA)-acetone, phenol, and TRIzol, in
      the eustigmatophyte alga Microchloropsis gaditana CCMP526 for proteomic analysis.
      M. gaditana is a potential candidate for algal-based biofuels. This industrially
      important strain is also rich in dietary oil and pigments and is used as feed in
      the aquaculture industry. Liquid chromatography-tandem mass spectrometry (LC
      MS/MS)-based proteomic analysis was performed for proteins obtained using the
      three extraction methods and their effects were examined by the abundance ratio.
      Protein yield was higher using the TCA-acetone and phenol methods than with the
      TRIzol method. The TCA method was superior than other methods examined here in
      terms of protein coverage and abundance. Subcellular localization of the
      identified proteins revealed no significant difference among the extraction
      methods. Importantly, each method revealed a unique set of proteins. To the best
      of our knowledge, this is the first report on evaluation of protein extraction
      methods for the proteomic analysis of M. gaditana CCMP526. These observations
      underscore the importance of using multiple protein extraction methods for
      comprehensive proteome coverage, as the field of proteomics edges toward diverse
      applications in biofuels, aquaculture industry, marine biology, and agriculture.

PMID- 29022838
TI  - Pharmacogenomics of triazole antifungal agents: implications for safety,
      tolerability and efficacy.
AB  - INTRODUCTION: Triazole antifungal agents are prescribed to treat invasive fungal
      infections in neutropenic and non-neutropenic patients. These antifungal agents
      are substrates and inhibitors of cytochrome P450 (CYP). Genetic polymorphisms in
      CYP2C9, CYP2C19 and CYP3A5 can lead to large population-specific variations in
      drug efficacy and safety, optimal dosing, or contribute to drug interactions
      associated with this class. Areas covered: This manuscript reviews the
      pharmacogenomics (i.e. the influence of genetics on drug disposition) of triazole
      antifungal agents related to their CYP-mediated metabolism and summarizes their
      implications on triazole efficacy, safety, and tolerability. A search of English
      language original research, and scholarly reviews describing the pharmacogenomics
      of triazole antifungal agents and their impact on drug efficacy, safety, and
      tolerability published from 1980 to present was undertaken using PubMed. Expert
      opinion: Currently studies demonstrating the pharmacogenomic influences on
      itraconazole, posaconazole and isavuconazole are minimal and limited to their
      inhibitory effects on CYP3A4 in expressors of CYP3A5 variants. Conversely, there
      are significant pharmacogenomic considerations for voriconazole because it
      interacts with several polymorphic CYPs, most notably CYP2C19. Pharmacogenomics
      of CYP2C9 do not appear to effect fluconazole safety and efficacy. However,
      genetic polymorphisms may influence its drug interactions but this needs further
      study.

PMID- 29022839
TI  - The Audacity of Engagement: Hearing Directly from Young Adults with Cancer on
      Their Attitudes and Perceptions of Cancer Survivorship and Cancer Survivorship
      Research.
AB  - BACKGROUND: Young adult (YA) cancer survivors have been historically under
      represented in cancer survivorship research, which has contributed to more
      disparate health outcomes compared with young and older cancer survivors. Using
      qualitative methods, this study explored YAs' perceptions of cancer survivorship
      and identified YA-specific barriers and preferences for participation in cancer
      survivorship research. METHODS: Individual interviews and focus groups were
      conducted with YA cancer survivors (N = 19) attending a patient-focused oncology
      conference. Grounded theory methodology guided analyses by using an inductive
      data-driven approach to thematic content analysis. RESULTS: Participants averaged
      33 years old (standard deviation [SD] = 5.5), were 10 years postdiagnosis (SD =
      2.3), and were primarily female (79%). Key cancer survivorship topics included
      adjusting to a "new normal," staying connected with cancer peers, and dealing
      with post-treatment medical care. Perceptions of YA survivorship research were
      mixed. YAs appreciated and were optimistic about the potential for benefit from
      research. Specific barriers for participation included perceptions of research
      being inaccessible, overwhelming, and frustrating; participation as inconvenient
      and burdensome; and researchers being viewed with skepticism and mistrust. They
      recommended: (1) making age-appropriate, patient-focused changes (e.g., language
      and design of study materials); (2) increasing participants' control,
      flexibility, and convenience of procedures; and (3) creating a back-and-forth
      dialogue between YAs and researchers. CONCLUSION: We assessed YA survivors'
      perceptions of YA cancer survivorship and research. Communication strategies are
      needed to address negative perceptions and perceived barriers to research
      participation. This includes tailoring of dissemination efforts and
      developmentally targeted implementation of YA priorities into the research
      process. Age-specific, patient-focused research practices may foster trust within
      the YA cancer survivor community and improve research participation.

PMID- 29022840
TI  - Irritable temperament and lifetime psychotic symptoms as predictors of anxiety
      symptoms in bipolar disorder.
AB  - PURPOSE: Affective temperaments, hopelessness, alexithymia, and anxiety/agitation
      symptoms may play a significant role in the psychopathological characteristics of
      bipolar disorder (BD). Here, we aimed to investigate the eventual association
      between the mentioned explanatory variables and anxiety/agitation symptoms in BD.
      MATERIALS AND METHODS: We recruited at the Section of Psychiatry, Department of
      Neuroscience, University of Genoa (Italy), 92 BD inpatients having a mean age of
      52 (+/-13.8) years. Participants were assessed using specific psychometric
      instruments. Anxiety/agitation symptoms have been evaluated using the 11-item of
      the Beck Depression Inventory II (BDI-II). RESULTS: Overall, 53.8% of
      participants presented with anxiety/agitation symptoms and 46.2% without. The two
      groups significantly differed about socio-economic status, lifetime psychotic
      symptoms, and residual depressive symptoms between episodes. Anxiety/agitation
      symptoms significantly correlated with irritable affective temperament (r =
      0.407; p = .01), hopelessness (r = 0.541; p <= .001), difficulty identifying
      feelings (r = 0.440; p <= .001), difficulty describing feelings (r = 0.437; p <=
      .001), and externally oriented-thinking (r = 0.393; p <= .001). After
      multivariate analyses, irritable affective temperament (OR = 2.457, p <= .01) and
      less lifetime psychotic symptoms (OR = 0.007, p <= .05) remained the only
      significant variables associated with anxiety/agitation symptoms. CONCLUSIONS:
      The generalization of the main findings is limited by the small sample size and
      cross-sectional study design. Nevertheless, our results suggest that the careful
      assessment of affective temperaments and psychotic symptoms may help to early
      identify BD patients suffering from anxiety/agitation symptoms and may allow to
      perform targeted interventions in the clinical practice.

PMID- 29022841
TI  - Designing cellulosic and nanocellulosic sensors for interface with a protease
      sequestrant wound-dressing prototype: Implications of material selection for
      dressing and protease sensor design.
AB  - Interfacing nanocellulosic-based biosensors with chronic wound dressings for
      protease point of care diagnostics combines functional material properties of
      high specific surface area, appropriate surface charge, and hydrophilicity with
      biocompatibility to the wound environment. Combining a protease sensor with a
      dressing is consistent with the concept of an intelligent dressing, which has
      been a goal of wound-dressing design for more than a quarter century. We present
      here biosensors with a nanocellulosic transducer surface (nanocrystals,
      nanocellulose composites, and nanocellulosic aerogels) immobilized with a
      fluorescent elastase tripeptide or tetrapeptide biomolecule, which has
      selectivity and affinity for human neutrophil elastase present in chronic wound
      fluid. The specific surface area of the materials correlates with a greater
      loading of the elastase peptide substrate. Nitrogen adsorption and mercury
      intrusion studies revealed gas permeable systems with different porosities (28
      98%) and pore sizes (2-50 nm, 210 um) respectively, which influence water vapor
      transmission rates. A correlation between zeta potential values and the degree of
      protease sequestration imply that the greater the negative surface charge of the
      nanomaterials, the greater the sequestration of positively charged neutrophil
      proteases. The biosensors gave detection sensitivities of 0.015-0.13 units/ml,
      which are at detectable human neutrophil elastase levels present in chronic wound
      fluid. Thus, the physical and interactive biochemical properties of the nano
      based biosensors are suitable for interfacing with protease sequestrant prototype
      wound dressings. A discussion of the relevance of protease sensors and cellulose
      nanomaterials to current chronic wound dressing design and technology is
      included.

PMID- 29022842
TI  - The effect of strontium-loaded rough titanium surface on early osseointegration.
AB  - It is not clear whether surface bioactive chemistry plays an important role in
      the early osseointegration of micro-structured titanium implants that have the
      same surface topography at the micrometer and submicrometer scales. In this
      study, magnetron sputtering methodology was employed for the preparation of Sr
      coating on sandblasted and acid-etched (SLA) titanium implant without changing
      the surface characteristics. The study of the surface morphology of the coating
      was carried out with the use of scanning electron microscopy, and the chemical
      composition of the surface was examined by X-ray energy-dispersive spectrometry.
      Twenty SLA implants together with 20 Sr-SLA implants were randomly inserted into
      the proximal tibia of 20 rats. The early osseointegration of the Sr-SLA implant
      was compared with SLA implant by removal torque test and histological analysis
      following two and eight weeks of implantation, correspondingly. As revealed by
      the surface characteristics, both Sr-SLA and SLA surfaces exhibited similar
      typical isotropic irregular indentations. The strontium ions were effectively
      incorporated into the SLA surface (the atomic ratio is 2%). Following two and
      eight weeks of healing, significant increases in removal torque values ( p <
      0.05) were taken into observation in respect of Sr-SLA implant. Histologically,
      the Sr-SLA implants displayed significantly higher bone-to-implant contact
      percentages and bone area ratio in comparison with the SLA implant at eight weeks
      ( p < 0.05). At two weeks, the bone-implant contact percentages, together with
      bone area ratio of Sr-SLA surface appeared to be a little bit slightly greater
      than that of SLA surface. But the statistical difference was not significant.
      These results indicated that the chemical modification with Sr incorporated by
      magnetron sputtering treatment in moderately rough surfaced implants remarkably
      increases early bone apposition.

PMID- 29022843
TI  - Should we treat aneurysms in perforator arteries from the basilar trunk? Review
      of 49 cases published in the literature and presentation of three personal cases.
AB  - Basilar trunk perforator artery aneurysms are rare. Their diagnosis and treatment
      are difficult, controversial, and challenging. Analysis of 52 cases (49
      documented in the literature and three personal cases) clearly shows a re
      bleeding rate of 15% in patients whose aneurysm has not been occluded and 0% in
      treated patients ( p < 0.05). The most effective treatment, and the one that
      presents the least complication, is double-stenting across the basilar trunk.

PMID- 29022844
TI  - Laser Biophotomodulation in Patients with Neurosensory Disturbance of the
      Inferior Alveolar Nerve After Sagittal Split Ramus Osteotomy: A 2-Year Follow-Up
      Study.
AB  - OBJECTIVE: To evaluate the effect of the application of photobiomodulation in a 2
      year follow-up period in patients who have been intervened with a sagittal ramus
      split osteotomy and present neurosensory disturbance of the inferior alveolar
      nerve. BACKGROUND: Photobiomodulation is a common clinical tool in dentistry, for
      its beneficial effects have been shown in surgical and periodontal wound healing,
      reducing of swelling and pain, neurosensory recovery, and treatment of
      temporomandibular joint disorders. METHODS: This is a 2-year follow-up study with
      an experimental (Laser) group (n = 33) that received photobiomodulation, and a
      control (Sham) group (n = 9), placebo. All patients from the Laser group received
      laser applications (continuous wave of 0.353 W/cm2, 27 J in 270 sec per session)
      on days 1, 2, 3, 5, 10, 14, 21, and 28 after surgery. Neurosensory disturbance
      was evaluated with five tests: Visual Analog Scale (VAS) for pain and
      sensitivity, sensitivity threshold test, two-point discrimination, and thermal
      discrimination. All tests were performed before (24 h before surgery) and after
      surgery (24 h, 28 days, 60 days, 6 months, 1 year, 2 years, more than 2 years).
      Participants and evaluator were blinded to intervention. Variables were described
      with absolute frequencies, percentages, and medians. Ordinal and dichotomous
      variables were compared with Mann-Whitney's and Fisher's tests, respectively.
      RESULTS: Clinical improvement was observed during the follow-up period for the
      Laser group; general VAS for sensitivity was normal in 11 participants from the
      Laser group at 2 years postsurgery (40.74%), while no participants from the Sham
      group achieved this (p = 0.0341). Twenty-three participants recovered initial
      values for two-point discrimination (69.7%) after 2 years of follow-up (p =
      0.0025) as well as sensitivity threshold test. General VAS for pain was normal in
      31 patients from the Laser group after 2 years of follow-up (93.94%, p = 0.0254).
      CONCLUSIONS: Photobiomodulation was effective for neurosensory recovery on sample
      studied.

PMID- 29022845
TI  - The Unified Patent Court: where are we and what should you be doing?
AB  - The road to the Unified Patent Court, which will allow industry to enforce its
      patents in Europe in a single set of proceedings rather than in numerous national
      courts, is becoming increasingly rocky as the project approaches its goal. This
      article reviews the rocks encountered in the past year and looks forward to what
      industry now needs to be addressing as the summit approaches.

PMID- 29022847
TI  - The Prison of Shame: Finding a Passage Through Dreams.
AB  - In New York City, a man and his therapist talk about shame as a psychological,
      bodily, gendered, and social experience that pervades even the consulting room.
      They describe and analyze trauma and guilt against the background of a common
      Mediterranean culture they experienced while growing up, albeit from different
      gendered and class positions. The patient's modest presenting complaint of
      blushing opens into an exploration that results in an unexpectedly profound
      transformation. Ultimately, therapy helps him acknowledge and process his
      traumatic experience of circumcision and other traumas. It frees him from deep
      seated shame, puts him in touch with new desires and needs, and helps him develop
      a more authentic sense of self and more balanced experience of his masculinity.
      The focus of this paper is on the patient's dreams as they were narrated and
      reexperienced in therapy: as stories within the story of therapy.

PMID- 29022848
TI  - The Theory and Art of Child Psychotherapy: A Corrective Developmental Approach.
AB  - The history of child psychotherapy is sketched from the psychoanalytic pioneers
      Anna Freud and Melanie Klein to the popular "nondirective" approach of Virginia
      Axline. The author's approach to child psychotherapy, based on contemporary
      psychoanalytic theories, allows the therapist to play any parental role that
      helps to repair developmental deficiencies and conflicts. These include
      nurturing, supporting, mirroring, role modeling, challenging, and limit setting.
      Following Winnicott, psychotherapy is conceived as a play space in which
      therapist and child are both spontaneous. The value of interpretation and insight
      in child therapy is discussed. There follows a more detailed discussion of three
      major problem areas in child psychotherapy: handling anger and hostile
      aggression; handling issues related to sexuality; and handling narcissistic
      issues of inferiority and shame.

PMID- 29022850
TI  - The Devolution of Melancholia Into Psychosis: The Case of a Child Whose Mother
      Was Unable to Grieve.
AB  - The author explores the intersubjective aspect of the devolution of melancholia
      into psychosis, particularly as it involves the unconscious intersubjective role
      of the mother. The author considers the possibility that maternal inability to
      mourn contributes significantly to the foreclosure of the child's "tertiary
      processes" (the processes involved in the child's development of a differentiated
      autonomous self and symbolization). In the clinical case presented in detail in
      this paper, the child's undifferentiated experience with his mother (who was
      unable to grieve) left no room for the father as the necessary third element in
      the child's maturational processes.

PMID- 29022851
TI  - Recurrent cisplatin hypersensitivity reaction after first exposure: A case
      report.
AB  - Purpose Hypersensitivity reactions to platinum-based chemotherapies are well
      documented and are often a limiting factor in treating a variety of cancers.
      Allergy skin testing has been used to determine if repeat exposure is safe. We
      report a case of a false negative skin allergy test in an atypical presentation
      of cisplatin hypersensitivity reaction. Case report A 64-year-old male diagnosed
      with stage IVa squamous cell carcinoma of the hypopharynx who developed a delayed
      reaction of face swelling and dysphagia following exposure to a single dose of
      cisplatin. Skin allergy testing performed and was negative. On second dosing of
      cisplatin, the patient developed an immediate hypersensitivity reaction.
      Cisplatin was discontinued, and the patient was transitioned to cetuximab. The
      rest of chemoradiation therapy was completed without further incident. Discussion
      This case demonstrates the limited efficacy of skin allergy testing for
      cisplatin. Furthermore, it is an atypical presentation of cisplatin-related
      hypersensitivity as it occurred following the patient's first dose despite no
      prior exposure to platinum-based chemotherapy. Conclusion Skin allergy testing
      has limited sensitivity for platinum-based chemotherapy and caution should be
      exercised in weighing risk and benefits of re-exposure. Although rare, cisplatin
      hypersensitivity can present after first exposure.

PMID- 29022852
TI  - Association Between Financial Incentives for Regional Care Coordination and
      Health Care Resource Utilization Among Older Patients after Femoral Neck Fracture
      Surgery: A Retrospective Cohort Study Using a Claims Database.
AB  - The incidence rates of hip fracture have been increasing in Japan. Length of stay
      among hip fracture patients in Japan is much longer than other developed
      countries, and the Japanese government introduced financial incentives for
      regionally coordinated femoral neck fracture care to reduce health care resource
      utilization. The objective of this study was to evaluate whether the financial
      incentives reduce health care resource utilization among patients 75 years or
      older with femoral neck fracture in Japan. Claims data from the Fukuoka
      Prefecture Regional Association for Late-Stage Healthcare for Older People were
      analyzed for the period from April 2010 to March 2016. The authors identified
      4641 eligible subjects after femoral neck fracture surgery, and categorized them
      into groups based on care pathways: coordinated care, integrated care, and other.
      Length of stay by care phase and total charges were used as measures of health
      care resource utilization. The models showed that coordinated and integrated care
      were significantly associated with shorter length of stay during perioperative
      care: coordinated care, multiplicative effect, 0.90 (P < 0.001); integrated care,
      0.77 (P < 0.001). However, only integrated care was associated with shorter
      rehabilitation and overall length of stay: 0.66 (P < 0.001) in rehabilitation;
      0.70 (P < 0.001) in overall duration. Integrated care also was associated with
      lower total charges: 0.70 (P < 0.001). Current financial incentives for
      regionally coordinated femoral neck fracture care do not affect health care
      resource utilization. Further health care reforms should be implemented to
      promote effective regional care coordination in Japan.

PMID- 29022853
TI  - Destination memory in social interaction: better memory for older than for
      younger destinations in normal aging?
AB  - Destination memory, a memory component allowing the attribution of information to
      its appropriate receiver (e.g., to whom did I lend my pen?), is compromised in
      normal aging. The present paper investigated whether older adults might show
      better memory for older destinations than for younger destinations. This
      hypothesis is based on empirical research showing better memory for older faces
      than for younger faces in older adults. Forty-one older adults and 44 younger
      adults were asked to tell proverbs to older and younger destinations (i.e.,
      coloured faces). On a later recognition test, participants had to decide whether
      they had previously told some proverb to an older/younger destination or not.
      Prior to this task, participants reported their frequency of contact with other
      age groups. The results showed lower destination memory in older adults than in
      younger adults. Interestingly, older adults displayed better memory for older
      than for younger destinations. The opposite pattern was seen in younger adults.
      The low memory for younger destinations, as observed in older adults, was
      significantly correlated with limited exposure to younger individuals. These
      findings suggest that for older adults, the social experience can play a crucial
      role in the destination memory, at least as far as exposure to other-age groups
      is concerned.

PMID- 29022854
TI  - Single-center mid-term experience with chimney-graft technique for the
      preservation of flow to the supra-aortic branches.
AB  - Objectives To investigate the feasibility and the mid-term outcomes of the
      chimney-graft technique for the revascularization of supra-aortic branches in
      patients with thoracic aortic pathologies involving the aortic arch. Methods A
      retrospective analysis of a prospectively maintained database between January
      2010 and July 2016 was performed. Primary endpoints were 30-day and overall
      mortality. Secondary endpoints were technical success, target vessel patency,
      stroke/transitory ischemic attack and type I/III endoleak rate. Results A total
      of 30 patients (80% male, median age 70.0 years) were treated using the chimney
      graft technique for the supra-aortic branches. The indication was a degenerative
      aneurysm in nine patients (32%) and a type B Stanford aortic dissection and a
      penetrating aortic ulcer in the descending aorta in seven patients (23%),
      respectively. In six patients (20.0%), the indication was an type Ia endoleak
      after previous endovascular thoracic repair, whereas a pseudoaneurysm after
      previous open repair of the descending aorta was the indication in one patient
      (3%). Twenty-three patients (77%) were treated electively, five (17%) emergently
      and two (7%) urgently because of free rupture. Technical success was achieved in
      90% of patients. The 30-day/in-hospital mortality was 17% (5/30). A retrograde
      dissection was presented in five patients. Four patients experienced a
      cerebrovascular event. Eight patients had type Ia endoleak and 10 had type II.
      During the median follow-up of 16 months (range: 0-56), four further patients
      died: one in respiratory insufficiency, one due to a ruptured abdominal aortic
      aneurysm, one in meningitis and the last one for unknown reason. The chimney
      graft patency was 100%. According to the Kaplan-Meier curve, the estimated
      survival at one year was 66 +/- 9%. Conclusions The chimney-graft technique,
      despite a technically demanding strategy, is a useful tool as bailout procedure
      in our armamentarium for high-risk patients, unsuitable for open or hybrid
      repair.

PMID- 29022855
TI  - Association of left subclavian artery coverage without revascularization and
      spinal cord ischemia in patients undergoing thoracic endovascular aortic repair:
      A Vascular Quality Initiative(r) analysis.
AB  - Objectives Investigate the impact of left subclavian artery coverage without
      revascularization on spinal cord ischemia development in patients undergoing
      thoracic endovascular aortic repair. Methods The Vascular Quality Initiative
      thoracic endovascular aortic repair module (April 2011-July 2014) was analyzed.
      Patients undergoing left subclavian artery coverage were divided into two groups
      according to revascularization status. The association between left subclavian
      artery revascularization with the primary outcome of spinal cord ischemia and the
      secondary outcome of stroke was assessed with multivariable analysis adjusting
      for between-group baseline differences. Results The left subclavian artery was
      covered in 508 (24.6%) of the 2063 thoracic endovascular aortic repairs
      performed. Among patients with left subclavian artery coverage, 58.9% underwent
      revascularization. Spinal cord ischemia incidence was 12.1% in the group without
      revascularization compared to 8.5% in the group undergoing left subclavian artery
      revascularization (odds ratio (95%CI): 1.48(0.82-2.68), P = 0.189). Multivariable
      analysis adjustment identified an independent association between left subclavian
      artery coverage without revascularization and the incidence of spinal cord
      ischemia (adjusted odds ratio (95%CI): 2.29(1.03-5.14), P = 0.043). Although the
      incidence of stroke was also higher for the group with a covered and
      nonrevascularized left subclavian artery (12.1% versus 8.5%), this difference was
      not statistically significant after multivariable analysis (adjusted odds ratio
      (95%CI): 1.55(0.74-3.26), P = 0.244). Conclusion For patients undergoing left
      subclavian artery coverage during thoracic endovascular aortic repair, the
      addition of a revascularization procedure was associated with a significantly
      lower incidence of spinal cord ischemia.

PMID- 29022857
TI  - Back to School: 2017.

PMID- 29022856
TI  - Hybrid technique for the management of thoracoabdominal aortic thrombosis and
      symptomatic Trans-Atlantic Inter-Society Consensus "C" aorto-iliac disease.
AB  - Objective Thrombotic disease of the thoracic and abdominal aorta co-existing with
      aorto-iliac disease is a rare clinical association, which poses a great
      therapeutic challenge and adds to the complexity of the open surgical repair.
      Method We describe a case of 53-year-old woman with symptomatic thrombus in the
      thoracic and abdominal aorta down to the aortic bifurcation, which was
      successfully treated by Thoracic EndoVascular Aortic Repair via the left
      subclavian artery, open thrombectomy and aorto-iliac bypass. Result Completion
      angiogram performed through the axillary cannula showed good flow in the aorta,
      visceral vessels and iliac arteries. Conclusion This hybrid technical approach
      was a safe and effective strategy to tackle diffuse aortic thrombus with minimal
      morbidity and visceral embolization. Simultaneous aorto bi iliac bypass with
      thoracic endovascular aortic repair is a viable approach that can be undertaken
      with lesser morbidity and mortality risk as compared to complex and highly
      stressful total open surgical repair.

PMID- 29022858
TI  - Formulation and characterization of alprazolam-loaded nanoliposomes: screening of
      process variables and optimizing characteristics using RSM.
AB  - This research study aimed to develop a novel sustained release formulation of
      alprazolam that can also be used for transdermal delivery. This was carried out,
      for the first time, through encapsulation of alprazolam in nanoliposomes using
      ethanol injection. In order to obtain the best formulation, four process
      variables, including the solvent/nonsolvent volume ratio, phospholipid
      concentration, alprazolam concentration, and cholesterol content were considered
      as key factors. Response surface methodology (RSM) and a central composite design
      (CCD) model were used to investigate the effect of these factors on vesicle size
      (VS) and encapsulation efficiency (EE) as the major properties of nanoliposomes.
      Experimental data were statistically analyzed, and two significant quadratic
      models were developed to test the VS and EE responses. The findings indicate that
      alprazolam and phospholipid concentrations have a significant effect on the mean
      VS. However, EE was significantly affected by both the alprazolam and
      phospholipid concentrations and the cholesterol content. The optimized
      formulation for preparation of alprazolam-loaded nanoliposomes with appropriate
      VS and EE was suggested. Small unilamellar vesicles (SUVs), ranging in size from
      50 to 100 nm were clearly observed in the transmission electron microscopy (TEM)
      images, which is appropriate for transdermal delivery of alprazolam. The study of
      the prepared nanoliposomes over 28 days at 4  degrees C confirmed the stability
      of the formulations containing cholesterol. The results of an in vitro release
      study of alprazolam-loaded nanoliposomes in phosphate buffered saline (PBS), pH
      7.4 for 24 h at 37  degrees C using dialysis, indicated the sustained release of
      alprazolam due to encapsulation.

PMID- 29022859
TI  - A Community-Based Study of Staphylococcus aureus Nasal Colonization and Molecular
      Characterization Among Men Who Have Sex with Men.
AB  - PURPOSE: The aims of this cross-sectional study were to determine the prevalence
      of Staphylococcus aureus nasal colonization, evaluate community-related
      behavioral risk factors, and utilize staphylococcal protein A (spa) typing for
      epidemiological surveillance among community-based men who have sex with men from
      the National HIV Behavioral Surveillance System in Houston, Texas. METHODS:
      Descriptive methods and logistic analyses were used to determine associations
      with nasal colonization. RESULTS: The prevalence of S. aureus colonization was
      29.7%; of these, 3.0% were colonized with methicillin-resistant S. aureus.
      Logistic analyses revealed that anal intercourse practices were associated with
      colonization (P < 0.05). A diverse population of 38 spa types was identified.
      CONCLUSION: Our findings suggest that an association among preferential sex
      practices, condom use, and S. aureus colonization exists and should be
      investigated further.

PMID- 29022861
TI  - Molecular characterization, prevalence and clinical relevance of Phodopus
      sungorus papillomavirus type 1 (PsuPV1) naturally infecting Siberian hamsters
      (Phodopus sungorus).
AB  - Phodopus sungorus papillomavirus type 1 (PsuPV1), naturally infecting Siberian
      hamsters (Phodopus sungorus) and clustering in the genus Pipapillomavirus (Pi
      PV), is only the second PV type isolated from the subfamily of hamsters. In
      silico analysis of three independent complete viral genomes obtained from
      cervical adenocarcinoma, oral squamous cell carcinoma and normal oral mucosa
      revealed that PsuPV1 encodes characteristic viral proteins (E1, E2, E4, E6, E7,
      L1 and L2) with conserved functional domains and a highly conserved non-coding
      region. The overall high prevalence (102/114; 89.5 %) of PsuPV1 infection in
      normal oral and anogenital mucosa suggests that asymptomatic infection with
      PsuPV1 is very frequent in healthy Siberian hamsters from an early age onward,
      and that the virus is often transmitted between both anatomical sites. Using type
      specific real-time PCR and chromogenic in situ hybridization, the presence of
      PsuPV1 was additionally detected in several investigated tumours (cervical
      adenocarcinoma, cervical adenomyoma, vaginal carcinoma in situ, ovarian granulosa
      cell tumour, mammary ductal carcinoma, oral fibrosarcoma, hibernoma and squamous
      cell papilloma) and normal tissues of adult animals. In the tissue sample of the
      oral squamous cell carcinoma individual, punctuated PsuPV1-specific in situ
      hybridization spots were detected within the nuclei of infected animal cells,
      suggesting viral integration into the host genome and a potential etiological
      association of PsuPV1 with sporadic cases of this neoplasm.

PMID- 29022863
TI  - Next-generation sequencing revealed divergence in deletions of the preS region in
      the HBV genome between different HBV-related liver diseases.
AB  - In order to investigate if deletion patterns of the preS region can predict liver
      disease advancement, the preS region of the hepatitis B virus (HBV) genome in 45
      chronic hepatitis B (CHB) and 94 HBV-related hepatocellular carcinoma (HCC)
      patients was sequenced by next-generation sequencing (NGS) and the percentages of
      nucleotide deletion in the preS region were analysed. Hierarchical clustering and
      heatmaps based on deletion percentages of preS revealed different deletion
      patterns between CHB and HCC patients. Intergenotype comparison also indicated
      divergence in preS deletions between HBV genotype B and C. No significant
      difference was found in preS deletion patterns between sera and matched adjacent
      non-tumour tissues. Based on hierarchical clustering, HCC patients were classed
      into two groups with different preS deletion patterns and different clinical
      features. Finally, the support vector machine (SVM) model was trained on preS
      nucleotide deletion percentages and used to predict HCC versus CHB patients. The
      prediction performance was assessed with fivefold cross-validation and
      independent cohort validation. The median area under the curve (AUC) was 0.729
      after repeating SVM 500 times with fivefold cross-validations. After parameter
      optimization, the SVM model was used to predict an independent cohort with 51 CHB
      patients and 72 HCC patients and the AUC was 0.727. In conclusion, the use of the
      NGS method revealed a prominent divergence in preS deletion patterns between
      disease groups and virus genotypes, but not between different tissue types.
      Quantitative NGS data combined with a machine learning method could be a powerful
      approach for prediction of the status of different diseases.

PMID- 29022864
TI  - Reverse genetic system, genetically stable reporter viruses and packaged
      subgenomic replicon based on a Brazilian Zika virus isolate.
AB  - Zika virus (ZIKV, genus Flavivirus) has emerged as a major mosquito-transmitted
      human pathogen, with recent outbreaks associated with an increased incidence of
      neurological complications, particularly microcephaly and the Guillain-Barre
      syndrome. Because the virus has only very recently emerged as an important
      pathogen, research is being hampered by a lack of reliable molecular tools. Here
      we report an infectious cDNA (icDNA) clone for ZIKV isolate BeH819015 from
      Brazil, which was selected as representative of South American ZIKV isolated at
      early stages of the outbreak. icDNA clones were assembled from synthetic DNA
      fragments corresponding to the consensus sequence of the BeH819015 isolate. Virus
      rescued from the icDNA clone had properties identical to a natural ZIKV isolate
      from South America. Variants of the clone-derived virus, expressing
      nanoluciferase, enhanced green fluorescent or mCherry marker proteins in both
      mammalian and insect cells and being genetically stable for multiple in vitro
      passages, were obtained. A ZIKV subgenomic replicon, lacking a prM- and E
      glycoprotein encoding region and expressing a Gaussia luciferase marker, was
      constructed and shown to replicate both in mammalian and insect cells. In the
      presence of the Semliki Forest virus replicon, expressing ZIKV structural
      proteins, the ZIKV replicon was packaged into virus-replicon particles. Efficient
      reverse genetic systems, genetically stable marker viruses and packaged replicons
      offer significant improvements for biological studies of ZIKV infection and
      disease, as well as for the development of antiviral approaches.

PMID- 29022862
TI  - Future research to underpin successful peste des petits ruminants virus (PPRV)
      eradication.
AB  - Peste des petits ruminants virus (PPRV) is a significant pathogen of small
      ruminants and is prevalent in much of Africa, the Near and Middle East and Asia.
      Despite the availability of an efficacious and cheap live-attenuated vaccine, the
      virus has continued to spread, with its range stretching from Morocco in the west
      to China and Mongolia in the east. Some of the world's poorest communities rely
      on small ruminant farming for subsistence and the continued endemicity of PPRV is
      a constant threat to their livelihoods. Moreover, PPRV's effects on the world's
      population are felt broadly across many economic, agricultural and social
      situations. This far-reaching impact has prompted the Food and Agriculture
      Organization of the United Nations (FAO) and the World Organisation for Animal
      Health (OIE) to develop a global strategy for the eradication of this virus and
      its disease. PPRV is a morbillivirus and, given the experience of these
      organizations in eradicating the related rinderpest virus, the eradication of
      PPRV should be feasible. However, there are many critical areas where basic and
      applied virological research concerning PPRV is lacking. The purpose of this
      review is to highlight areas where new research could be performed in order to
      guide and facilitate the eradication programme. These areas include studies on
      disease transmission and epidemiology, the existence of wildlife reservoirs and
      the development of next-generation vaccines and diagnostics. With the support of
      the international virology community, the successful eradication of PPRV can be
      achieved.

PMID- 29022865
TI  - Toscana virus cap-snatching and initiation of transcription.
AB  - Toscana virus (TOSV) is an arthropod-borne phlebovirus within the family
      Phenuiviridae in the order Bunyavirales. It seems to be an important agent of
      human meningoencephalitis in the warm season in the Mediterranean area. Because
      the polymerase of Bunyavirales lacks a capping activity, it cleaves short-capped
      RNA leaders derived from the host cell, and uses them to initiate viral mRNA
      synthesis. To determine the size and nucleotide composition of the host-derived
      RNA leaders, and to elucidate the first steps of TOSV transcription initiation,
      we performed a high-throughput sequencing of the 5' end of TOSV mRNAs in infected
      cells at different times post-infection. Our results indicated that the viral
      polymerase cleaved the host-capped RNA leaders within a window of 11-16
      nucleotides. A single population of cellular mRNAs could be cleaved at different
      sites to prime the synthesis of several viral mRNA species. The majority of the
      mRNA resulted from direct priming, but we observed mRNAs resulting from several
      rounds of prime-and-realign events. Our data suggest that the different rounds of
      the prime-and-realign mechanism result from the blocking of the template strand
      in a static position in the active site, leading to the slippage of the nascent
      strand by two nucleotides when the growing duplex is sorted out from the active
      site. To minimize this rate-limiting step, TOSV polymerase cleaves preferentially
      capped RNA leaders after GC, so as to greatly reduce the number of cycles of
      priming and realignment, and facilitate the separation of the growing duplex.

PMID- 29022866
TI  - ICTV Virus Taxonomy Profile: Hepeviridae.
AB  - The family Hepeviridae includes enterically transmitted small non-enveloped
      positive-sense RNA viruses. It includes the genera Piscihepevirus, whose members
      infect fish, and Orthohepevirus, whose members infect mammals and birds. Members
      of the genus Orthohepevirus include hepatitis E virus, which is responsible for
      self-limiting acute hepatitis in humans and several mammalian species; the
      infection may become chronic in immunocompromised individuals. Extrahepatic
      manifestations of Guillain-Barre syndrome, neuralgic amyotrophy,
      glomerulonephritis and pancreatitis have been described in humans. Avian
      hepatitis E virus causes hepatitis-splenomegaly syndrome in chickens. This is a
      summary of the International Committee on Taxonomy of Viruses (ICTV) Report on
      the taxonomy of the Hepeviridae, which is available at
      www.ictv.global/report/hepeviridae.

PMID- 29022867
TI  - Response to photo-oxidative stress of Pseudomonas aeruginosa PAO1 mutants
      impaired in different functions.
AB  - Clinicians often have to deal with infections that are difficult to control
      because they are caused by superbugs resistant to many antibiotics. Alternatives
      to antibiotic treatment include antimicrobial photodynamic therapy (aPDT). The
      photodynamic process causes bacterial death, inducing oxidative stress through
      the photoactivation of photosensitizer molecules in the presence of oxygen. No
      PDT-resistant bacteria have been selected to date, thus the response to photo
      oxidative stress in non-phototrophic bacteria needs further investigation. The
      opportunistic pathogen Pseudomonas aeruginosa, in particular, has been shown to
      be more tolerant to PDT than other micro-organisms. In order to find any genetic
      determinants involved in PDT-tolerance, a panel of transposon mutants of P.
      aeruginosa PAO1 involved in the quorum sensing signalling system and membrane
      cytoplasmic transport were photoinactivated as part of this study. Two
      pseudomonas quinolone signalling (PQS) knock-out mutants, pqsH- and pqsC-, were
      as PDT-sensitive as the PAO1 wild-type strains. Two PQS hyperproducer variants,
      pqsA- and rsaL-, were shown to be more tolerant to photo-oxidative stress than
      the wild-type strain. In the pqsA- mutant, the hyperpigmentation due to the
      presence of phenazines could protect cells against PDT stress, while in rsaL- no
      pigmentation was detectable. Furthermore, a mutant impaired in an ATP-binding
      cassette transport involved in maintaining the asymmetry of the outer membrane
      was significantly more tolerant to photo-oxidative stress than the wild-type
      strain. These observations support the involvement of quorum sensing and the
      importance of the bacterial cell envelope when dealing with photo-oxidative
      stress induced by photodynamic treatment.

PMID- 29022868
TI  - The nitrogen-regulated response regulator NrrA is a conserved regulator of
      glycogen catabolism in beta-cyanobacteria.
AB  - Cyanobacteria acclimatize to nitrogen deprivation by changing cellular
      metabolism. The nitrogen-regulated response regulator A (NrrA) is involved in
      regulation of carbon metabolism in response to nitrogen deprivation. However, it
      has not been elucidated whether these regulatory functions of NrrA are particular
      to a few model strains or are general among diverse cyanobacteria. In this study,
      we showed that regulation and functions of NrrA were highly conserved among beta
      cyanobacteria, which included physiologically and ecologically diverse strains.
      All beta-cyanobacteria had the nrrA gene, while it was absent in alpha
      cyanobacteria. The canonical NtcA-dependent promoter sequence was found upstream
      of the nrrA genes in most beta-cyanobacteria, and its expression was indeed
      induced by nitrogen deprivation. Biochemical and physiological analyses of NrrA
      from phylogenetically distinct cyanobacteria indicated that regulation of NrrA
      activity and NrrA functions, namely activation of glycogen catabolism, were also
      common to beta-cyanobacteria. These results support the conclusion that NrrA
      plays an important role in acclimatization to nitrogen deprivation, and that
      activation of glycogen catabolism is a primitive response to nitrogen deprivation
      in beta-cyanobacteria.

PMID- 29022869
TI  - Dynamic regulatory interaction between cytomegalovirus major tegument protein
      pp65 and protein kinase pUL97 in intracellular compartments, dense bodies and
      virions.
AB  - Human cytomegalovirus (HCMV) is a ubiquitous pathogen of considerable clinical
      importance. Understanding the processes that are important for viral replication
      is essential for the development of therapeutic strategies against HCMV
      infection. The HCMV-encoded protein kinase pUL97 is an important multifunctional
      regulator of viral replication. Several viral and cellular proteins are
      phosphorylated by pUL97. The phosphoprotein pp65 is one important substrate of
      pUL97. It is the most abundant tegument protein of HCMV virions, mediating the
      upload of other virion constituents and contributing to particle integrity.
      Further to that, it interferes with host innate immune defences, thereby enabling
      efficient viral replication. By applying different approaches, we characterized
      the pp65-pUL97 interaction in various compartments. Specifically, the pUL97
      interaction domain of pp65 was defined (282-415). A putative cyclin bridge that
      enhances pUL97-pp65 interaction was identified. The impact of pUL97 mutation on
      virion and dense body morphogenesis was addressed using pUL97 mutant viruses.
      Alterations in the proteome of viral particles were seen, especially with mutant
      viruses expressing cytoplasmic variants of pUL97. On the basis of these data we
      postulate a so far poorly recognized functional relationship between pp65 and
      pUL97, and present a refined model of pp65-pUL97 interaction.

PMID- 29022871
TI  - A postmortem analysis of NMDA ionotropic and group 1 metabotropic glutamate
      receptors in the nucleus accumbens in schizophrenia.
AB  - BACKGROUND: The nucleus accumbens (NAcc) has been implicated in the pathology and
      treatment of schizophrenia. Recent postmortem evidence suggests a
      hyperglutamatergic state in the NAcc. With the present study we aimed to explore
      possible glutamatergic alterations in the NAcc of a large schizophrenia cohort.
      METHODS: We performed immunoblots on postmortem NAcc samples from 30 individuals
      who had schizophrenia and 30 matched controls. We examined the protein expression
      of primary glutamatergic receptors, including the N-methyl-D-aspartate (NMDA)
      receptor (NR1, NR2A and NR2B subunits) and the group 1 metabotropic glutamate
      receptor (mGluR1 and mGluR5; dimeric and monomeric forms). In addition, we
      measured the group 1 mGluR endogenous regulators, neurochondrin and Homer1b/c,
      which have recently been implicated in the pathophysiology of schizophrenia.
      RESULTS: Protein levels of glutamatergic receptors and endogenous regulators were
      not significantly different between the controls and individuals who had
      schizophrenia. Furthermore, mGluR5, but not mGluR1, showed a positive association
      with NMDA receptor subunits, suggesting differential interactions between these
      receptors in this brain region. LIMITATIONS: Investigation of these proteins in
      antipsychotic-naive individuals, in addition to the subregions of the NAcc and
      subcellular fractions, will strengthen future studies. CONCLUSION: The present
      study does not provide evidence for glutamatergic abnormalities within the NAcc
      of individuals with schizophrenia. Taken together with the results of previous
      studies, these findings suggest NMDA receptors and group 1 mGluRs are altered in
      a brain region-dependent manner in individuals with schizophrenia. The
      differential associations between mGluR1, mGluR5 and NMDA receptors observed in
      this study warrant further research into the interactions of these proteins and
      the implications for the therapeutic and adverse effect profile of glutamatergic
      based novel therapeutics.

PMID- 29022870
TI  - Molecular characterization of Porcine sapelovirus in Hunan, China.
AB  - Porcine sapeloviruses (PSVs) are widely distributed in pig populations; however,
      little information on their evolutionary history and the mechanisms driving their
      divergence is available. Therefore, in the present study, 241 fecal samples and
      91 intestinal contents collected from pigs at 26 farms in Hunan, China, were
      tested for the presence of PSVs. The overall PSV positivity rate was 46.39 %,
      with a particularly high infection rate detected in nursery and fattening pigs. A
      total of 29 PSV strains (PSV-HuNs) were isolated, with these showing high genetic
      diversity based on phylogenetic and pairwise distance analyses of the capsid
      protein gene sequences. Incongruence between phylognetic trees of the capsid
      protein and 3CD regions indicated frequent recombination within the PSV-HuNs, and
      a putative recombinant hotspot near the 3' end of the P1 region was identified.
      Our results suggested that recombination played an important role in driving PSV
      genetic diversity and evolution.

PMID- 29022873
TI  - Adolescent THC exposure in female rats leads to cognitive deficits through a
      mechanism involving chromatin modifications in the prefrontal cortex.
AB  - BACKGROUND: Increasing cannabis consumption among adolescents, studies that link
      its early use with mental illnesses, and the political debate on cannabis
      legalization together call for an urgent need to study molecular underpinnings of
      adolescent brain vulnerability. The emerging role of epigenetic mechanisms in
      psychiatric diseases led us to hypothesize that epigenetic alterations could play
      a role in causes and subsequent development of the depressive/psychotic-like
      phenotype induced by adolescent, but not adult, Delta9-tetrahydrocannabinol (THC)
      exposure in female rats. METHODS: We performed a time-course analysis of histone
      modifications, chromatin remodelling enzymes and gene expression in the
      prefrontal cortex of female rats after adolescent and adult THC exposure. We also
      administered a specific epigenetic drug (chaetocin) with THC to investigate its
      impact on THC-induced behavioural alterations. RESULTS: Adolescent THC exposure
      induced alterations of selective histone modifications (mainly H3K9me3),
      impacting the expression of genes closely associated with synaptic plasticity.
      Changes in both histone modifications and gene expression were more widespread
      and intense after adolescent treatment, suggesting specific adolescent
      susceptibility. Adolescent THC exposure significantly increased Suv39H1 levels,
      which could account for the enhanced H3K9me3. Pharmacological blockade of H3K9me3
      during adolescent THC treatment prevented THC-induced cognitive deficits,
      suggesting the relevant role played by H3K9me3 in THC-induced effects.
      LIMITATIONS: Only female rats were investigated, and the expression studies were
      limited to a specific subset of genes. CONCLUSION: Through a mechanism involving
      SUV39H1, THC modifies histone modifications and, thereby, expression of
      plasticity genes. This pathway appears to be relevant for the development of
      cognitive deficits.

PMID- 29022872
TI  - Arterial stiffness is associated with depression in middle-aged men - the
      Maastricht Study.
AB  - BACKGROUND: Arterial stiffening may underlie the association between depression
      and cardiovascular disease (CVD), but reported data are inconsistent. We
      investigated the associations between aortic stiffness and major depressive
      disorder (MDD) and depressive symptoms, and whether these differed by sex and
      age. METHODS: We measured carotid to femoral pulse wave velocity (cfPWV) using
      applanation tonometry, and we assessed depression using the Mini-International
      Neuropsychiatric Interview (MINI) and the Patient Health Questionnaire-9 (PHQ-9)
      in a cohort of participants from The Maastricht Study. Logistic and negative
      binominal models were adjusted for age, type 2 diabetes mellitus (T2DM), mean
      arterial pressure (MAP) and CVD risk factors. RESULTS: We included 2757
      participants in our analyses (48.8% men, mean age 59.8 +/- 8.1 yr, 27% T2DM). We
      found that cfPWV was associated with MDD in men (fully adjusted odds ratio [OR]
      2.36, 95% confidence interval [CI] 1.45-3.84), but not in women (OR 1.57, 95% CI
      0.93-2.66), aged 60 years or younger. The ORs were not significant in individuals
      older than 60 years (men: OR 1.03, 95% CI 0.63-1.68; women: OR 0.64, 95% CI 0.32
      1.31). Similarly, cfPWV was associated with a higher PHQ-9 score in men (rate
      ratio 1.28, 95% CI 1.09-1.52), but not in women (rate ratio 1.11, 95% CI 0.99
      1.23), aged 60 years or younger. Associations were not significant in individuals
      older than 60 years (men: rate ratio 0.96, 95% CI 0.84-1.08; women: rate ratio
      1.00, 95% CI 0.90-1.12). LIMITATIONS: We cannot rule out reversed causation in
      this cross-sectional study. CONCLUSION: Greater aortic stiffness is associated
      with MDD and depressive symptoms among middle-aged men and to a lesser extent in
      women, whereas this association was not observed in old age.

PMID- 29022874
TI  - Uncoupling of dynamin polymerization and GTPase activity revealed by the
      conformation-specific nanobody dynab.
AB  - Dynamin is a large GTPase that forms a helical collar at the neck of endocytic
      pits, and catalyzes membrane fission (Schmid and Frolov, 2011; Ferguson and De
      Camilli, 2012). Dynamin fission reaction is strictly dependent on GTP hydrolysis,
      but how fission is mediated is still debated (Antonny et al., 2016): GTP energy
      could be spent in membrane constriction required for fission, or in disassembly
      of the dynamin polymer to trigger fission. To follow dynamin GTP hydrolysis at
      endocytic pits, we generated a conformation-specific nanobody called dynab, that
      binds preferentially to the GTP hydrolytic state of dynamin-1. Dynab allowed us
      to follow the GTPase activity of dynamin-1 in real-time. We show that in
      fibroblasts, dynamin GTP hydrolysis occurs as stochastic bursts, which are
      randomly distributed relatively to the peak of dynamin assembly. Thus, dynamin
      disassembly is not coupled to GTPase activity, supporting that the GTP energy is
      primarily spent in constriction.

PMID- 29022876
TI  - Local processing in neurites of VGluT3-expressing amacrine cells differentially
      organizes visual information.
AB  - Neurons receive synaptic inputs on extensive neurite arbors. How information is
      organized across arbors and how local processing in neurites contributes to
      circuit function is mostly unknown. Here, we used two-photon Ca2+ imaging to
      study visual processing in VGluT3-expressing amacrine cells (VG3-ACs) in the
      mouse retina. Contrast preferences (ON vs. OFF) varied across VG3-AC arbors
      depending on the laminar position of neurites, with ON responses preferring
      larger stimuli than OFF responses. Although arbors of neighboring cells overlap
      extensively, imaging population activity revealed continuous topographic maps of
      visual space in the VG3-AC plexus. All VG3-AC neurites responded strongly to
      object motion, but remained silent during global image motion. Thus, VG3-AC
      arbors limit vertical and lateral integration of contrast and location
      information, respectively. We propose that this local processing enables the
      dense VG3-AC plexus to contribute precise object motion signals to diverse
      targets without distorting target-specific contrast preferences and spatial
      receptive fields.

PMID- 29022875
TI  - Spatio-temporal control of mutualism in legumes helps spread symbiotic nitrogen
      fixation.
AB  - Mutualism is of fundamental importance in ecosystems. Which factors help to keep
      the relationship mutually beneficial and evolutionarily successful is a central
      question. We addressed this issue for one of the most significant mutualistic
      interactions on Earth, which associates plants of the leguminosae family and
      hundreds of nitrogen (N2)-fixing bacterial species. Here we analyze the spatio
      temporal dynamics of fixers and non-fixers along the symbiotic process in the
      Cupriavidus taiwanensis-Mimosa pudica system. N2-fixing symbionts progressively
      outcompete isogenic non-fixers within root nodules, where N2-fixation occurs,
      even when they share the same nodule. Numerical simulations, supported by
      experimental validation, predict that rare fixers will invade a population
      dominated by non-fixing bacteria during serial nodulation cycles with a
      probability that is function of initial inoculum, plant population size and
      nodulation cycle length. Our findings provide insights into the selective forces
      and ecological factors that may have driven the spread of the N2-fixation
      mutualistic trait.

PMID- 29022877
TI  - Striatal adenosine A2A receptor neurons control active-period sleep via
      parvalbumin neurons in external globus pallidus.
AB  - Dysfunction of the striatum is frequently associated with sleep disturbances.
      However, its role in sleep-wake regulation has been paid little attention even
      though the striatum densely expresses adenosine A2A receptors (A2ARs), which are
      essential for adenosine-induced sleep. Here we showed that chemogenetic
      activation of A2AR neurons in specific subregions of the striatum induced a
      remarkable increase in non-rapid eye movement (NREM) sleep. Anatomical mapping
      and immunoelectron microscopy revealed that striatal A2AR neurons innervated the
      external globus pallidus (GPe) in a topographically organized manner and
      preferentially formed inhibitory synapses with GPe parvalbumin (PV) neurons.
      Moreover, lesions of GPe PV neurons abolished the sleep-promoting effect of
      striatal A2AR neurons. In addition, chemogenetic inhibition of striatal A2AR
      neurons led to a significant decrease of NREM sleep at active period, but not
      inactive period of mice. These findings reveal a prominent contribution of
      striatal A2AR neuron/GPe PV neuron circuit in sleep control.

PMID- 29022878
TI  - Stochastic variation in the initial phase of bacterial infection predicts the
      probability of survival in D. melanogaster.
AB  - A central problem in infection biology is understanding why two individuals
      exposed to identical infections have different outcomes. We have developed an
      experimental model where genetically identical, co-housed Drosophila given
      identical systemic infections experience different outcomes, with some
      individuals succumbing to acute infection while others control the pathogen as an
      asymptomatic persistent infection. We found that differences in bacterial burden
      at the time of death did not explain the two outcomes of infection. Inter
      individual variation in survival stems from variation in within-host bacterial
      growth, which is determined by the immune response. We developed a model that
      captures bacterial growth dynamics and identifies key factors that predict the
      infection outcome: the rate of bacterial proliferation and the time required for
      the host to establish an effective immunological control. Our results provide a
      framework for studying the individual host-pathogen parameters governing the
      progression of infection and lead ultimately to life or death.

PMID- 29022881
TI  - Primary HIV infection in patients with acute hepatitis B: a report of two cases.
AB  - We describe two patients admitted to our institution with a diagnosis of sexually
      acquired acute hepatitis B who also had underlying hyper acute HIV infection.
      Both individuals reported high rates of condomless sex. Antiviral therapy active
      against HBV and HIV was started within days after diagnosis. Treatment was well
      tolerated and led to a rapid control of both infections and hepatitis B surface
      antibody seroconversion. The efficacy and safety of contemporary antiretroviral
      drug combinations suggest that treatment of acute HIV infection is feasible in
      patients with acute hepatitis B.

PMID- 29022882
TI  - Friction effect of stator in a multi-walled CNT-based rotation transmission
      system.
AB  - The rotation transmission system (RTS) made from co-axial multi-walled nanotubes
      (MWNTs) has the function of regulating the input rotation from a nanomotor. The
      mechanism for the regulation is that the friction among the tubes during rotation
      governs the rotation of the rotors in the nanosystem. By integrating a rotary
      nanomotor and a nanobearing into an MWNT-based RTS, it is discovered that the
      stator (outer tube) provides relatively greater friction on the rotors by
      penetrating the motor tube, which has a higher stable rotational frequency. And
      the output rotation of the rotors in the system depends significantly on the
      temperature of the system, as the rotor tubes are slightly longer than the motor
      tube. Briefly, at low temperatures, say 8 K, the rotors rotate synchronously with
      the motor. However, at high temperatures, the rotors rotate slower than the motor
      with a bigger difference between their rotational frequencies. Hence, the output
      rotational frequencies can be adjusted by changing the temperature as well as the
      input rotational frequency.

PMID- 29022879
TI  - Sparse genetic tracing reveals regionally specific functional organization of
      mammalian nociceptors.
AB  - The human distal limbs have a high spatial acuity for noxious stimuli but a low
      density of pain-sensing neurites. To elucidate mechanisms underlying regional
      differences in processing nociception, we sparsely traced non-peptidergic
      nociceptors across the body using a newly generated MrgprdCreERT2 mouse line. We
      found that mouse plantar paw skin is also innervated by a low density of Mrgprd+
      nociceptors, while individual arbors in different locations are comparable in
      size. Surprisingly, the central arbors of plantar paw and trunk innervating
      nociceptors have distinct morphologies in the spinal cord. This regional
      difference is well correlated with a heightened signal transmission for plantar
      paw circuits, as revealed by both spinal cord slice recordings and behavior
      assays. Taken together, our results elucidate a novel somatotopic functional
      organization of the mammalian pain system and suggest that regional central arbor
      structure could facilitate the "enlarged representation" of plantar paw regions
      in the CNS.

PMID- 29022883
TI  - Statistical analysis of the reduction process of graphene oxide probed by Raman
      spectroscopy mapping.
AB  - We propose a method for monitoring the large-scale homogeneity of the reduction
      process of graphene oxide. For this purpose, a Raman mapping technique is
      employed to probe the evolution of the phonon properties of two different
      graphene oxide (GO) thin films upon controllable thermal reduction. The reduction
      of GO is reflected by the upshift of the statistical distribution of the relative
      intensity ratio of the G and D peaks (I D/I G) of the Raman spectra and is
      consistent with the ratio obtained for chemically reduced GO. In addition, the
      shifts of the position distributions of the main Raman modes ([Formula: see
      text], [Formula: see text]) and their cross-correlation with the I D/I G ratio
      provides evidence of a change of the doping level, demonstrating the influence of
      reduction processes on GO films.

PMID- 29022884
TI  - Reply to 'Comment on Photoplethysmography sampling frequency: pilot assessment of
      how low can we go to analyze pulse rate variability with reliability?'
AB  - In his Comment, Hejjel argued that some contents previously published by us were
      inappropriate for the statistical analysis of pulse rate variability due to high
      inter-individual dispersion. He also claimed that data collection over 5 min for
      short-term HRV analysis and data collection for an abnormal range of people were
      required. In order to give our perspective on these issues, we will discuss and
      clarify some of the existing literature and our own work on this subject,
      underlining the difference between electrocardiogram and photoplethysmogram.

PMID- 29022880
TI  - Genetically tunable frustration controls allostery in an intrinsically disordered
      transcription factor.
AB  - Intrinsically disordered proteins (IDPs) present a functional paradox because
      they lack stable tertiary structure, but nonetheless play a central role in
      signaling, utilizing a process known as allostery. Historically, allostery in
      structured proteins has been interpreted in terms of propagated structural
      changes that are induced by effector binding. Thus, it is not clear how IDPs,
      lacking such well-defined structures, can allosterically affect function. Here,
      we show a mechanism by which an IDP can allosterically control function by
      simultaneously tuning transcriptional activation and repression, using a novel
      strategy that relies on the principle of 'energetic frustration'. We demonstrate
      that human glucocorticoid receptor tunes this signaling in vivo by producing
      translational isoforms differing only in the length of the disordered region,
      which modulates the degree of frustration. We expect this frustration-based model
      of allostery will prove to be generally important in explaining signaling in
      other IDPs.

PMID- 29022885
TI  - Comment on 'Photoplethysmography sampling frequency: pilot assessment of how low
      can we go to analyze pulse rate variability with reliability?'
AB  - Accurate pulse rate detection is essential for reliable pulse rate variability
      analysis. On the other hand, minimizing the sampling frequency is essential to
      reduce the amount of data and computational needs, and consequently the power
      consumption of mobile/wearable devices, extending their operating hours.
      Determining the variability of physiological parameters needs a new paradigm
      since there is a limited possibility of calculating an average eliminating random
      error of measurement. Finding the optimal sampling rate depends on the actual
      investigation, the expected variability and variability-changes of the study
      population in order to get valid HRV parameters.

PMID- 29022886
TI  - Computational methods for 2D materials: discovery, property characterization, and
      application design.
AB  - The discovery of two-dimensional (2D) materials comes at a time when
      computational methods are mature and can predict novel 2D materials, characterize
      their properties, and guide the design of 2D materials for applications. This
      article reviews the recent progress in computational approaches for 2D materials
      research. We discuss the computational techniques and provide an overview of the
      ongoing research in the field. We begin with an overview of known 2D materials,
      common computational methods, and available cyber infrastructures. We then move
      onto the discovery of novel 2D materials, discussing the stability criteria for
      2D materials, computational methods for structure prediction, and interactions of
      monolayers with electrochemical and gaseous environments. Next, we describe the
      computational characterization of the 2D materials' electronic, optical,
      magnetic, and superconducting properties and the response of the properties under
      applied mechanical strain and electrical fields. From there, we move on to
      discuss the structure and properties of defects in 2D materials, and describe
      methods for 2D materials device simulations. We conclude by providing an outlook
      on the needs and challenges for future developments in the field of computational
      research for 2D materials.

PMID- 29022887
TI  - Delocalized versus localized excitations in the photoisomerization of azobenzene
      functionalized alkanethiolate SAMs.
AB  - Self-assembled monolayers of azobenzene-functionalized alkanethiolates form
      molecular ensembles with preferential orientation and significant excitonic
      coupling among the azobenzene chromophores. We have studied their optical
      switching with differential reflectance and two-photon-photoemission spectroscopy
      tuning the excitation wavelength through the excitonically broadened S2
      absorption band. While the effective isomerization cross-section increases
      towards shorter wavelengths, the fraction of cis molecules in the photostationary
      state decreases. We attribute this observation to the absorption of the cis
      isomer in the SAM. The photoisomerization in the SAM thereby follows the behavior
      of non-interacting chromophores in solution, despite the formation of H
      aggregates. Our study thus reveals that photoswitching occurs via localized
      excitations while strongly excitonically coupled, delocalized states do not
      contribute significantly.

PMID- 29022888
TI  - Is there a link between mitochondrial DNA and blood pressure?

PMID- 29022889
TI  - ARMC5 is not implicated in familial hyperaldosteronism type II (FH-II).

PMID- 29022890
TI  - Elevated microRNA-34a contributes to trophoblast cell apoptosis in preeclampsia
      by targeting BCL-2.
AB  - Preeclampsia (PE) is one of the most common pregnancy-specific pathologic
      complications, and is characterised by onset of hypertension and proteinuria.
      Placental trophoblast cell apoptosis is generally accepted as a major cause of
      PE. However, the details of the mechanism underlying the condition remain
      unclear. Here, we aimed to investigate a possible association between microRNA
      (miR)-34a and human trophoblast cell apoptosis during PE. We evaluated miR-34a
      expression in placentas from patients with PE compared with those from healthy
      pregnant individuals. Furthermore, we measured apoptosis rate after miR-34a mimic
      and/or inhibitor transfection in vitro, and identified B-cell CLL/lymphoma 2 (BCL
      2) as a target of miR-34a. We found that miR-34a levels were significantly higher
      in placental tissues from patients with PE than in normal placentas. Upregulation
      of miR-34a induced trophoblast cell apoptosis in PE by inhibiting expression of
      BCL-2 protein. miR-34a inhibition reversed miR-34a-induced apoptosis in the HTR
      8/SVneo human trophoblast cell line. Our findings indicate that miR-34a may be
      linked to the occurrence of PE via effects on BCL-2 in the human placenta, and
      may therefore provide a potential therapeutic target for PE.

PMID- 29022891
TI  - Escin induces caspase-dependent apoptosis and autophagy through the ROS/p38 MAPK
      signalling pathway in human osteosarcoma cells in vitro and in vivo.
AB  - Osteosarcoma is one of the most malignant neoplasms in adolescents, and it
      generally develops multidrug resistance. Escin, a natural mixture of triterpene
      saponins isolated from Aesculus hippocastanum (horse chestnut), has demonstrated
      potent anti-tumour potential in vitro and in vivo. In the present study, we found
      that escin inhibited osteosarcoma proliferation in a dose- and time-dependent
      manner. Additionally, escin-induced apoptosis was evidenced by the increased
      expression of caspase-related proteins and the formation of apoptotic bodies.
      Escin also induced autophagy, with elevated LC3, ATG5, ATG12 and Beclin
      expression as well as autophagosome formation. Inhibition of escin-induced
      autophagy promoted apoptosis. Moreover, p38 mitogen-activated protein kinases
      (MAPKs) and reactive oxygen species (ROS) were activated by escin. A p38 MAPK
      inhibitor partially attenuated the autophagy and apoptosis triggered by escin,
      but a ROS scavenger showed a greater inhibitory effect. Finally, the therapeutic
      efficacy of escin against osteosarcoma was demonstrated in an orthotopic model.
      Overall, escin counteracted osteosarcoma by inducing autophagy and apoptosis via
      the activation of the ROS/p38 MAPK signalling pathway; these findings provide
      evidence for escin as a novel and potent therapeutic for the treatment of
      osteosarcoma.

PMID- 29022892
TI  - The lncRNA HULC functions as an oncogene by targeting ATG7 and ITGB1 in
      epithelial ovarian carcinoma.
AB  - Highly upregulated in liver cancer (HULC) is a long noncoding RNA (lncRNA), which
      has recently been identified as a key regulator in the progression of
      hepatocellular carcinoma, gliomas and gastric cancer. However, its role in
      epithelial ovarian carcinoma (EOC) remains unknown. In this study, HULC
      expression was examined in EOC, borderline and benign ovarian tumors, and normal
      ovarian tissues by RT-PCR. Ovarian cancer cell phenotypes, as well as autophagy
      associated proteins were examined after HULC overexpression or downregulation by
      plasmid or small interfering RNA (siRNA) transfection, respectively. LncRNA
      protein interactions were examined by ribonucleoprotein immunoprecipitation (RIP)
      assays. We found that HULC expression levels were higher in EOC tissues than
      normal samples. HULC overexpression induced cell proliferation, migration,
      invasion, whereas reduced cell apoptosis in vitro and induced tumor growth in
      vivo. In contrast, downregulation of HULC by siRNA transfection reduced cell
      proliferation, migration and invasion, and induced cell apoptosis and autophagy.
      Our results showed that HULC overexpression reduced ATG7, LC3-II and LAMP1
      expression, while inducing SQSTM1 (P62) and ITGB1 expression. HULC downregulation
      had the opposite effects. Furthermore, RIP indicated that ATG7 interacted with
      HULC; ATG7 downregulation also induced cell proliferation, reduced apoptosis and
      inhibited autophagy in vitro by reducing LC3-II and LAMP1 expression, while
      inducing SQSTM1 expression. Furthermore, ATG7 co-transfection with HULC reversed
      the oncogenic effects of HULC both in vitro and in vivo; however, downregulating
      ATG7 did not affect cell migration and invasive ability. We found that ITGB1
      siRNA co-transfection with HULC reversed the function of HULC in inducing ovarian
      cancer cell migration and invasive ability. Taken together, our results show that
      HULC may promote ovarian carcinoma tumorigenesis by inhibiting ATG7 and inducing
      progression by regulating ITGB1.

PMID- 29022893
TI  - MYCN contributes to the malignant characteristics of erythroleukemia through EZH2
      mediated epigenetic repression of p21.
AB  - MYC proto-oncogene family including c-myc and n-myc (MYCN) are critical for
      normal cell development and tumorigenesis. Overexpression of c-myc causes acute
      erythroleukemia in vivo. However, the role of MYCN in acute erythroleukemia
      remains poorly understood. In this study, we found that the patients with
      erythroleukemia showed higher expression of MYCN than normal controls. In vitro
      experiments, knockdown of MYCN resulted in decreased cell proliferation, elevated
      autonomously cell apoptosis and increased P21-mediated cell senescence. On the
      contrary, overexpression of MYCN obviously promoted cell proliferation, and
      induced erythroid differentiation block and apoptosis resistance to cytotoxic
      agent. Further gene microarray and functional analysis revealed that EZH2 is a
      target of MYCN. Knockdown of MYCN inhibited the expression of EZH2, and then
      activated p21 expression through removal of H3K27me3 at the p21 promoter.
      Overexpression of ezh2 could antagonize the p21 activation caused by MYCN
      knockdown. In addition, Aurora inhibitor MLN8237 inhibited the proliferation of
      erythroleukemia cells through repression of MYCN/EZH2 axis, whereas it minimally
      affected the normal hematopoietic cells. In conclusion, MYCN contributes to the
      malignant characteristics of erythroleukemia through EZH2-meidated epigenetic
      repression of p21. MYCN may serve as a therapy target for the patients with acute
      erythroleukemia.

PMID- 29022894
TI  - Adiponectin controls the apoptosis and the expression of tight junction proteins
      in brain endothelial cells through AdipoR1 under beta amyloid toxicity.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disease,
      characterized by excessive beta amyloid (Abeta) deposition in brain, leading to
      blood-brain barrier (BBB) disruption. The mechanisms of BBB disruption in AD are
      still unclear, despite considerable research. The adipokine adiponectin is known
      to regulate various metabolic functions and reduce inflammation. Though
      adiponectin receptors have been reported in the brain, its role in the central
      nervous system has not been fully characterized. In the present study, we
      investigate whether adiponectin contributes to the tight junction integrity and
      cell death of brain endothelial cells under Abeta-induced toxicity conditions. We
      measured the expression of adiponectin receptors (AdipoR1 and AdipoR2) and the
      alteration of tight junction proteins in in vivo 5xFAD mouse brain. Moreover, we
      examined the production of reactive oxygen species (ROS) and the loss of tight
      junction proteins such as Claudin 5, ZO-1, and inflammatory signaling in in vitro
      brain endothelial cells (bEnd.3 cells) under Abeta toxicity. Our results showed
      that Acrp30 (a globular form of adiponectin) reduces the expression of
      proinflammatory cytokines and the expression of RAGE as Abeta transporters into
      brain. Moreover, we found that Acrp 30 attenuated the apoptosis and the tight
      junction disruption through AdipoR1-mediated NF-kappaB pathway in Abeta-exposed
      bEnd.3 cells. Thus, we suggest that adiponectin is an attractive therapeutic
      target for treating BBB breakdown in AD brain.

PMID- 29022895
TI  - Impairment of PTX3 expression in osteoblasts: a key element for osteoporosis.
AB  - Pentraxin 3 (PTX3) is a multifunctional glycoprotein regulating inflammatory
      response, cell proliferation and migration and deposition and remodelling of the
      extracellular matrix by a variety of cells. In this study, we investigated the
      possible role of PTX3 in bone homeostasis. To this end, we compared the
      expression and function of PTX3 in human osteoblasts of osteoporotic,
      osteoarthritic patients and young subjects not affected by bone diseases.
      Immunohistochemical analysis performed on bone head biopsies showed a close
      association between bone health and the number of osteoblasts expressing PTX3.
      Noteworthy, the proportion of PTX3-positive osteoblasts resulted to be
      significantly lower in osteoporotic patients compared with both young patients
      and osteoarthritic patients of the same age. Ex vivo culture of osteoblasts
      isolated from the three groups of patients confirmed in vivo observation.
      Specifically, we observed rare runt-related transcription factor 2 (RUNX2)
      immunopositive osteoblasts expressing PTX3 in cell cultures derived from
      osteoporotic patients and western blotting analysis showed 80% reduction of PTX3
      in the corresponding culture extracts compared with young and osteoarthritic
      patients. The treatment of human osteoblast primary cultures derived from young
      patients with anti-PTX3 antibody dramatically affected osteoblast behaviour.
      Indeed, they lost the morphological and molecular features typical of mature
      osteoblasts, acquiring fibroblast-like shape and highly decreasing nuclear factor
      kappa-B ligand (RANKL) and RUNX2 expression. Also, the inhibition of PTX3
      negatively affected osteoblast proliferation and their ability to form cell
      clusters and microhydroxyapatite crystals. Altogether, these results suggest a
      central role of PTX3 in bone homeostasis showing its involvement in osteoblast
      proliferation, differentiation and function.

PMID- 29022896
TI  - MicroRNA-378 protects against intestinal ischemia/reperfusion injury via a
      mechanism involving the inhibition of intestinal mucosal cell apoptosis.
AB  - Intestinal ischemia/reperfusion (I/R) injury remains a major clinical event and
      contributes to high morbidity and mortality rates, but the underlying mechanisms
      remain elusive. Recent studies have demonstrated that microRNAs (miRNAs) have
      important roles in organ I/R injury, but the changes and potential roles of
      miRNAs in intestinal I/R-induced intestinal injury are unclear. This study was
      designed to analyze the miRNA expression profiles in intestinal mucosa after I/R
      injury and to explore the role of target miRNA during this process. Using miRNA
      microarray analysis, we found changes of 19 miRNAs from the expression profile of
      miRNAs in a mouse model of intestinal I/R and further verified them by RT-qPCR.
      Here, we report that miR-378 is one of the markedly decreased miRNAs and found
      the putative target mRNA that is linked to cell death after applying the
      TargetScan, miRanda, CLIP-Seq and miRDB prediction algorithms. Our results show
      that the overexpression of miR-378 significantly ameliorated intestinal tissue
      damage in wild-type and transgenic mice and oxygen glucose
      deprivation/reperfusion-challenged IEC-6 cell injury. Moreover, miR-378
      overexpression reduced intestinal epithelial cell apoptosis in both in vivo and
      in vitro ischemic models and attenuated cleaved caspase-3 expression.
      Collectively, our results revealed that the suppression of caspase-3 activation
      by miRNA-378 overexpression may be involved in the protective effects of
      intestinal ischemic damage. MiRNA-378 may serve as a key regulator and
      therapeutic target in intestinal I/R injury.

PMID- 29022897
TI  - Cooperation of Rel family members in regulating Abeta1-40-mediated pro
      inflammatory cytokine secretion by retinal pigment epithelial cells.
AB  - Amyloid-beta (Abeta) is a hallmark component of age-related macular degeneration
      (AMD), which induces secretion of pro-inflammatory cytokines from retinal pigment
      epithelium (RPE). Previous studies have shown that p50/RelA (p65), a member of NF
      kappaB family, is an essential pro-inflammatory transcription factor responding
      to Abeta1-40 stimulation, but few focused on the other two Rel transcription
      factor members - RelB and c-Rel - and their role in Abeta1-40-mediated
      inflammation. It was reported that RelA, RelB and c-Rel are also implicated in
      various NF-kappaB-mediated inflammatory diseases. Therefore, we infer that Abeta1
      40-mediated inflammation targets not only the classical inflammation regulator,
      RelA, but also RelB and c-Rel. In this study, we demonstrate that intravitreally
      injected Abeta1-40 mice develop AMD-like pathologic changes, coupled with Rel
      protein (RelA, RelB and c-Rel) synthesis and nuclear translocation. To focus on
      the interaction mechanism of Rel proteins, we found that RelB and c-Rel formed a
      heterodimer with RelA in mice model. We also found that c-Rel silencing decreased
      the levels of Abeta1-40-dependent RelA expression, indicating that RelB and c-Rel
      may interact with RelA as coactivator and c-Rel is required to activate the
      expression of RelA. Moreover, Rel protein silencing decreased the expression of
      distinct pro-inflammatory cytokines. Together, we demonstrate that besides RelA,
      RelB and c-Rel can also be activated by Abeta1-40, all of which mediate pro
      inflammatory cytokine transcription and RPE damage. Our findings imply that RPE
      mediated inflammation under the stimulation of Abeta1-40 is multi-targeted and
      RelA, RelB and c-Rel proteins may be the new targets of anti-inflammatory agents.

PMID- 29022898
TI  - Superoxide drives progression of Parkin/PINK1-dependent mitophagy following
      translocation of Parkin to mitochondria.
AB  - Reactive oxygen species (ROS) and mitophagy are profoundly implicated in the
      pathogenesis of neurodegenerative diseases, such as Parkinson's disease (PD).
      Several studies have suggested that ROS are not involved in mitochondrial
      translocation of Parkin which primes mitochondria for autophagic elimination.
      However, whether ROS play a role in the execution of mitophagy is unknown. In the
      present study, we show that carbonyl cyanide m-chlorophenylhydrazone (CCCP)
      treatment induced both mitochondrial depolarization and generation of ROS that
      were needed for the mitophagy process. Cells failed to proceed to complete
      mitophagy if CCCP treatment was discontinued even after recruitment of Parkin and
      autophagy machinery to mitochondria. Notably, treatment of pro-oxidant was able
      to replace CCCP treatment to take mitophagy forward, while it alone was
      insufficient to induce translocation of Parkin to mitochondria or autophagic
      clearance of mitochondria. In addition, an SOD mimetic that attenuated the
      superoxide level suppressed mitophagy, while an SOD inhibitor accumulated
      cellular superoxide and promoted mitophagy. Furthermore, blockage of the p38
      signaling pathway inhibited mitophagy induced by ROS, suggesting that it may
      contribute to the activation of ROS-mediated mitophagy. Together, our study sheds
      light on the link between ROS and mitophagy at a molecular level, and suggests
      the therapeutic potential of regulating mitophagy through the superoxide-p38
      mitophagy axis.

PMID- 29022899
TI  - Transplanted human p75-positive stem Leydig cells replace disrupted Leydig cells
      for testosterone production.
AB  - Previous studies have demonstrated that rodent stem Leydig cell (SLC)
      transplantation can partially restore testosterone production in Leydig cell (LC)
      disrupted or senescent animal models, which provides a promising approach for the
      treatment of hypogonadism. Here, we isolated human SLCs prospectively and
      explored the potential therapeutic benefits of human SLC transplantation for
      hypogonadism treatment. In adult human testes, p75 neurotrophin receptor positive
      (p75+) cells expressed the known SLC marker nestin, but not the LC lineage marker
      hydroxysteroid dehydrogenase-3beta (HSD3beta). The p75+ cells which were sorted
      by flow cytometry from human adult testes could expand in vitro and exhibited
      clonogenic self-renewal capacity. The p75+ cells had multi-lineage
      differentiation potential into multiple mesodermal cell lineages and testosterone
      producing LCs in vitro. After transplantation into the testes of ethane dimethane
      sulfonate (EDS)-treated LC-disrupted rat models, the p75+ cells differentiated
      into LCs in vivo and secreted testosterone in a physiological pattern. Moreover,
      p75+ cell transplantation accelerated the recovery of serum testosterone levels,
      spermatogenesis and reproductive organ weights. Taken together, we reported a
      method for the identification and isolation of human SLCs on the basis of p75
      expression, and demonstrated that transplanted human p75+ SLCs could replace
      disrupted LCs for testosterone production. These findings provide the groundwork
      for further clinical application of human SLCs for hypogonadism.

PMID- 29022900
TI  - Increased 15-lipoxygenase-1 expression in chondrocytes contributes to the
      pathogenesis of osteoarthritis.
AB  - 15-Lipoxygenase-1 (15-LO-1) is involved in many pathological processes. The
      purpose of this study was to determine the potential role of 15-LO-1 in
      osteoarthritis (OA). The levels of 15-LO-1 expression were measured by western
      blotting and quantitative real-time PCR in articular cartilage from the OA rat
      models and OA patients. To further investigate the effects of 15-LO-1 on
      chondrocyte functions, such as extracellular matrix (ECM) secretion, the release
      of matrix-degrading enzymes, the production of reactive oxygen species (ROS),
      cell proliferation and apoptosis, we decreased or increased 15-LO-1 expression in
      chondrocytes by means of transfecting with siRNA targeting 15-LO-1 and plasmid
      encoding 15-LO-1, respectively. The results showed that 15-LO-1 expression was
      obviously increased in articular cartilage from OA rats and OA patients. It was
      also found that many factor-related OA, such as mechanical loading, ROS, SNP and
      inflammatory factor, significantly promoted 15-LO-1 expression and activity in
      chondrocytes. Silencing 15-LO-1 was able to markedly alleviate mechanical loading
      induced cartilage ECM secretion, cartilage-degrading enzyme secretion and ROS
      production. Overexpression of 15-LO-1 could inhibit chondrocyte proliferation and
      induce chondrocyte apoptosis. In addition, reduction of 15-LO-1 in vivo
      significantly alleviated OA. Taken together, these results indicate that 15-LO-1
      has an important role in the disease progression of OA. Thus 15-LO-1 may be a
      good target for developing drugs in the treatment of OA.

PMID- 29022901
TI  - BCR-ABL1-induced downregulation of WASP in chronic myeloid leukemia involves
      epigenetic modification and contributes to malignancy.
AB  - Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the BCR
      ABL1 tyrosine kinase (TK). The development of TK inhibitors (TKIs) revolutionized
      the treatment of CML patients. However, TKIs are not effective to those at
      advanced phases when amplified BCR-ABL1 levels and increased genomic instability
      lead to secondary oncogenic modifications. Wiskott-Aldrich syndrome protein
      (WASP) is an important regulator of signaling transduction in hematopoietic cells
      and was shown to be an endogenous inhibitor of the c-ABL TK. Here, we show that
      the expression of WASP decreases with the progression of CML, inversely
      correlates with the expression of BCR-ABL1 and is particularly low in blast
      crisis. Enforced expression of BCR-ABL1 negatively regulates the expression of
      WASP. Decreased expression of WASP is partially due to DNA methylation of the
      proximal WASP promoter. Importantly, lower levels of WASP in CML advanced phase
      patients correlate with poorer overall survival (OS) and is associated with TKI
      response. Interestingly, enforced expression of WASP in BCR-ABL1-positive K562
      cells increases the susceptibility to apoptosis induced by TRAIL or
      chemotherapeutic drugs and negatively modulates BCR-ABL1-induced tumorigenesis in
      vitro and in vivo. Taken together, our data reveal a novel molecular mechanism
      that operates in BCR-ABL1-induced tumorigenesis that can be used to develop new
      strategies to help TKI-resistant, CML patients in blast crisis (BC).

PMID- 29022902
TI  - Differential regulation of spermatogenic process by Lkb1 isoforms in mouse
      testis.
AB  - Liver serine/threonine kinase B1 (LKB1) is a tumor suppressor associated with the
      pathogenesis of Peutz-Jeghers syndrome. Affected males are at increased risk of
      developing Sertoli cell tumors and display defective spermatogenesis. Male mice
      lacking the short isoform (Lkb1S) of Lkb1 were sterile and exhibited abnormal
      spermiogenesis. In addition to the short isoform, the long isoform of Lkb1
      (Lkb1L) is also expressed in testis; however, the requirement of the long isoform
      for fertility and the functional difference between the isoforms remain unknown.
      Herein, different from the spermiation failure reported in Lkb1S knockout mice,
      conditional deletion (cKO) of both isoforms of Lkb1 in germ cells resulted in
      male sterility stemming from defects in acrosome formation, as well as nuclear
      elongation and condensation during spermatid differentiation. Additionally, cKO
      mice showed a progressive germ cell loss that was never reported in mice with
      Lkb1S deletion. Further experiments revealed that the defect resulted from the
      failure of spermatogonial stem/progenitor cells (SPCs) maintenance. Although
      increased mTORC1 activity in postnatal cKO testes was consistent with a tendency
      toward germline stem cell differentiation, in vivo inhibition of the pathway by
      rapamycin treatment failed to rescue the phenotype. Concurrently, we detected a
      significant reduction of mitochondrial activity in Lkb1deficient SPCs. The
      results suggest that the regulation of LKB1 on SPCs' maintenance is associated
      with mitochondrial functions but not through the mTOR signaling pathway. In
      summary, our study supports different roles of Lkb1 isoforms in spermatogenesis
      with Lkb1L directing SPCs maintenance, and Lkb1L and Lkb1S coordinately
      regulating spermatid differentiation.

PMID- 29022905
TI  - c-Abl-mediated Drp1 phosphorylation promotes oxidative stress-induced
      mitochondrial fragmentation and neuronal cell death.
AB  - Oxidative stress-induced mitochondrial dysfunction and neuronal cell death have
      important roles in the development of neurodegenerative diseases. Dynamin related
      protein 1 (Drp1) is a critical factor in regulating mitochondrial dynamics. A
      variety of posttranslational modifications of Drp1 have been reported, including
      phosphorylation, ubiquitination, sumoylation and S-nitrosylation. In this study,
      we found that c-Abl phosphorylated Drp1 at tyrosine 266, 368 and 449 in vitro and
      in vivo, which augmented the GTPase activity of Drp1 and promoted Drp1-mediated
      mitochondrial fragmentation. Consistently, c-Abl-mediated phosphorylation is
      important for GTPase activity of Drp1 and mitochondrial fragmentation.
      Furthermore, we found that Drp1 phosphorylation mediated by c-Abl is required for
      oxidative stress-induced cell death in primary cortical neurons. Taken together,
      our findings reveal that c-Abl-Drp1 signaling pathway regulates oxidative stress
      induced mitochondrial fragmentation and cell death, which might be a potential
      target for the treatment of neurodegenerative diseases.

PMID- 29022904
TI  - Zika virus infection dysregulates human neural stem cell growth and inhibits
      differentiation into neuroprogenitor cells.
AB  - The current outbreak of Zika virus-associated diseases in South America and its
      threat to spread to other parts of the world has emerged as a global health
      emergency. A strong link between Zika virus and microcephaly exists, and the
      potential mechanisms associated with microcephaly are under intense
      investigation. In this study, we evaluated the effect of Zika virus infection of
      Asian and African lineages (PRVABC59 and MR766) in human neural stem cells
      (hNSCs). These two Zika virus strains displayed distinct infection pattern and
      growth rates in hNSCs. Zika virus MR766 strain increased serine 139
      phosphorylation of histone H2AX (gammaH2AX), a known early cellular response
      proteins to DNA damage. On the other hand, PRVABC59 strain upregulated serine 15
      phosphorylation of p53, p21 and PUMA expression. MR766-infected cells displayed
      poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavage. Interestingly,
      infection of hNSCs by both strains of Zika virus for 24 h, followed by incubation
      in astrocyte differentiation medium, induced rounding and cell death. However,
      astrocytes generated from hNSCs by incubation in differentiation medium when
      infected with Zika virus displayed minimal cytopathic effect at an early time
      point. Infected hNSCs incubated in astrocyte differentiating medium displayed
      PARP cleavage within 24-36 h. Together, these results showed that two distinct
      strains of Zika virus potentiate hNSC growth inhibition by different mechanisms,
      but both viruses strongly induce death in early differentiating neuroprogenitor
      cells even at a very low multiplicity of infection. Our observations demonstrate
      further mechanistic insights for impaired neuronal homeostasis during active Zika
      virus infection.

PMID- 29022903
TI  - Alternative mechanisms of miR-34a regulation in cancer.
AB  - MicroRNA miR-34a is recognized as a master regulator of tumor suppression. The
      strategy of miR-34a replacement has been investigated in clinical trials as the
      first attempt of miRNA application in cancer treatment. However, emerging
      outcomes promote the re-evaluation of existing knowledge and urge the need for
      better understanding the complex biological role of miR-34a. The targets of miR
      34a encompass numerous regulators of cancer cell proliferation, survival and
      resistance to therapy. MiR-34a expression is transcriptionally controlled by p53,
      a crucial tumor suppressor pathway, often disrupted in cancer. Moreover, miR-34a
      abundance is fine-tuned by context-dependent feedback loops. The function and
      effects of exogenously delivered or re-expressed miR-34a on the background of
      defective p53 therefore remain prominent issues in miR-34a based therapy. In this
      work, we review p53-independent mechanisms regulating the expression of miR-34a.
      Aside from molecules directly interacting with MIR34A promoter, processes
      affecting epigenetic regulation and miRNA maturation are discussed. Multiple
      mechanisms operate in the context of cancer-associated phenomena, such as
      aberrant oncogene signaling, EMT or inflammation. Since p53-dependent tumor
      suppressive mechanisms are disturbed in a substantial proportion of malignancies,
      we summarize the effects of miR-34a modulation in cell and animal models in the
      clinically relevant context of disrupted or insufficient p53 function.

PMID- 29022906
TI  - Increasing AR by HIF-2alpha inhibitor (PT-2385) overcomes the side-effects of
      sorafenib by suppressing hepatocellular carcinoma invasion via alteration of
      pSTAT3, pAKT and pERK signals.
AB  - Although sorafenib is currently used as a standard treatment for advanced
      hepatocellular carcinoma, low response rate, transient and limited efficacy,
      primary and acquired resistance and negative side-effects gain increasing
      attentions, suggesting the need for better efficacious combination therapy. Here,
      we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible
      factor (HIF)-2alpha could bind to an hypoxia responsive element within 500 bp
      region of androgen receptor (AR) promoter and thus transcriptionally suppress AR.
      Importantly, In vitro and In vivo studies suggested a specific and potent HIF
      2alpha inhibitor, PT-2385, could significantly enhance sorafenib efficacy by
      suppressing HIF-2alpha, increasing AR and suppressing downstream pSTAT3/pAKT/pERK
      pathways. Clinical samples further confirmed the role of HIF-2alpha and AR. It is
      promising that PT-2385 could alleviate the undesirable side-effects of sorafenib
      treatment by sorafenib-PT-2385 combination therapy, which may shed light for late
      stage HCC patients.

PMID- 29022907
TI  - p38alpha MAPK antagonizing JNK to control the hepatic fat accumulation in
      pediatric patients onset intestinal failure.
AB  - The p38alpha mitogen-activated protein kinase (MAPK) has been related to
      gluconeogenesis and lipid metabolism. However, the roles and related mechanisms
      of p38alpha MAPK in intestinal failure (IF)-associated liver steatosis remained
      poor understood. Here, our experimental evidence suggested that p38alpha MAPK
      significantly suppressed the fat accumulation in livers of IF patients mainly
      through two mechanisms. On the one hand, p38alpha MAPK increased hepatic bile
      acid (BA) synthesis by upregulating the expression of the rate-limiting enzyme
      cholesterol 7-alpha-hydroxylase (CYP7A1) and peroxisome proliferator-activated
      receptor gamma coactivator-1alpha (PGC-1alpha), which in turn activated the
      transcription of the CYP7A1. On the other hand, p38alpha MAPK promoted fatty acid
      (FA) beta-oxidation via upregulating peroxisome proliferator-activated receptor
      alpha (PPARalpha) and its transcriptional target genes carnitine
      palmitoyltransferase 1A (CPT1A) and peroxisomal acyl-coenzyme aoxidase 1 (ACOX1).
      Dual luciferase assays indicated that p38alpha MAPK increased the transcription
      of PPARalpha, PGC-1alpha and CYP7A1 by upregulating their promoters' activities.
      In addition, in vitro and in vivo assays indicated p38alpha MAPK negatively
      regulates the hepatic steatosis by controlling JNK activation. In conculsion, our
      findings demonstrate that hepatic p38alpha MAPK functions as a negative regulator
      of liver steatosis in maintaining BA synthesis and FAO by antagonizing the c-Jun
      N-terminal kinase (JNK).

PMID- 29022908
TI  - miR-143 and miR-145 inhibit gastric cancer cell migration and metastasis by
      suppressing MYO6.
AB  - Metastasis is a major clinical obstacle responsible for the high mortality and
      poor prognosis of gastric cancer (GC). MicroRNAs (miRNAs) are critical mediators
      of metastasis that act by modulating their target genes. In this study, we found
      that miR-143 and miR-145 act via a common target gene, MYO6, to regulate the
      epithelial-mesenchymal transition (EMT) and inhibit metastasis. We determined
      that miR-143 and miR-145 were downregulated in GC, and the ectopic expression of
      miR-143 and/or miR-145 inhibited GC cell migration and metastasis. Furthermore,
      MYO6 was identified as a direct common target of miR-143 and miR-145 and was
      elevated in GC. Silencing of MYO6 resulted in a metastasis-suppressive activity
      similar to that of miR-143 and miR-145, while restoring MYO6 attenuated the anti
      metastatic or anti-EMT effects caused by miR-143 and miR-145. Clinically, an
      inverse correlation was observed between miR-143/145 levels and MYO6 levels in GC
      tissues, and either miR-143/145 downregulation or MYO6 upregulation was
      associated with more malignant phenotypes in patients with GC. In conclusion, miR
      143 and miR-145 suppress GC cell migration and metastasis by inhibiting MYO6
      expression and the EMT, which provides a novel mechanism and promising
      therapeutic target for the treatment of GC metastasis.

PMID- 29022909
TI  - miR-216a inhibits osteosarcoma cell proliferation, invasion and metastasis by
      targeting CDK14.
AB  - Osteosarcoma (OS) has emerged as the most common primary musculoskeletal
      malignant tumour affecting children and young adults. Cyclin-dependent kinases
      (CDKs) are closely associated with gene regulation in tumour biology.
      Accumulating evidence indicates that the aberrant function of CDK14 is involved
      in a broad spectrum of diseases and is associated with clinical outcomes.
      MicroRNAs (miRNAs) are crucial epigenetic regulators in the development of OS.
      However, the essential role of CDK14 and the molecular mechanisms by which miRNAs
      regulate CDK14 in the oncogenesis and progression of OS have not been fully
      elucidated. Here we found that CDK14 expression was closely associated with poor
      prognosis and overall survival of OS patients. Using dual-luciferase reporter
      assays, we also found that miR-216a inhibits CDK14 expression by binding to the
      3'-untranslated region of CDK14. Overexpression of miR-216a significantly
      suppressed cell proliferation, migration and invasion in vivo and in vitro by
      inhibiting CDK14 production. Overexpression of CDK14 in the miR-216a-transfected
      OS cells effectively rescued the suppression of cell proliferation, migration and
      invasion caused by miR-216a. In addition, Kaplan-Meier analysis indicated that
      miR-216a expression predicted favourable clinical outcomes for OS patients.
      Moreover, miR-216a expression was downregulated in OS patients and was negatively
      associated with CDK14 expression. Overall, these data highlight the role of the
      miR-216a/CDK14 axis as a novel pleiotropic modulator and demonstrate the
      associated molecular mechanisms, thus suggesting the intriguing possibility that
      miR-216a activation and CDK14 inhibition may be novel and attractive therapeutic
      strategies for treating OS patients.

PMID- 29022910
TI  - Long non-coding RNA Myd88 promotes growth and metastasis in hepatocellular
      carcinoma via regulating Myd88 expression through H3K27 modification.
AB  - Enhanced Myd88 expression has been found in various parenchymal tumors especially
      in hepatocellular carcinoma with little mechanism of its upregulation known. A
      lot of long non-coding RNAs are reported to regulate the protein-coding genes
      which have location association through various mechanisms. In our study we
      confirmed a new long non-coding RNA Myd88 aberrant upregulated in HCC located
      upstream of Myd88 and verified a positive regulation relationship between them
      indicating that Lnc-Myd88 might participate in the enhanced expression of Myd88
      in HCC. The gain- and loss-of-function analysis revealed that Lnc-Myd88 could
      promote the proliferation and metastasis of HCC both in vitro and in vivo. In
      addition, ChIP assays demonstrated that Lnc-Myd88 might increase Myd88 expression
      through enhancing H3K27Ac in the promoter of Myd88 gene, thus resulting in the
      activation of both NF-kappaB and PI3K/AKT signal pathways. In conclusion, we
      proposed that Lnc-Myd88 might serve as a novel diagnosis and therapeutic target
      for HCC.

PMID- 29022911
TI  - The level of caveolin-1 expression determines response to TGF-beta as a tumour
      suppressor in hepatocellular carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) is a heterogeneous tumour associated with poor
      prognostic outcome. Caveolin-1 (CAV1), a membrane protein involved in the
      formation of caveolae, is frequently overexpressed in HCC. Transforming growth
      factor-beta (TGF-beta) is a pleiotropic cytokine having a dual role in
      hepatocarcinogenesis: inducer of apoptosis at early phases, but pro-tumourigenic
      once cells acquire mechanisms to overcome its suppressor effects. Apoptosis
      induced by TGF-beta is mediated by upregulation of the NADPH oxidase NOX4, but
      counteracted by transactivation of the epidermal growth factor receptor (EGFR)
      pathway. Previous data suggested that CAV1 is required for the anti-apoptotic
      signals triggered by TGF-beta in hepatocytes. Whether this mechanism is relevant
      in hepatocarcinogenesis has not been explored yet. Here we analysed the TGF-beta
      response in HCC cell lines that express different levels of CAV1. Accordingly,
      stable CAV1 knockdown or overexpressing cell lines were generated. We demonstrate
      that CAV1 is protecting HCC cells from TGF-beta-induced apoptosis, which
      attenuates its suppressive effect on clonogenic growth and increases its effects
      on cell migration. Downregulation of CAV1 in HLE cells promotes TGF-beta-mediated
      induction of the pro-apoptotic BMF, which correlates with upregulation of NOX4,
      whereas CAV1 overexpression in Huh7 cells shows the opposite effect. CAV1
      silenced HLE cells show attenuation in TGF-beta-induced EGFR transactivation and
      activation of the PI3K/AKT pathway. On the contrary, Huh7 cells, which do not
      respond to TGF-beta activating the EGFR pathway, acquire the capacity to do so
      when CAV1 is overexpressed. Analyses in samples from HCC patients revealed that
      tumour tissues presented higher expression levels of CAV1 compared with
      surrounding non-tumoural areas. Furthermore, a significant positive correlation
      among the expression of CAV1 and TGFB1 was observed. We conclude that CAV1 has an
      essential role in switching the response to TGF-beta from cytostatic to
      tumourigenic, which could have clinical meaning in patient stratification.

PMID- 29022912
TI  - Tenomodulin is essential for prevention of adipocyte accumulation and
      fibrovascular scar formation during early tendon healing.
AB  - Tenomodulin (Tnmd) is the best-known mature marker for tendon and ligament
      lineage cells. It is important for tendon maturation, running performance and has
      key implications for the resident tendon stem/progenitor cells (TSPCs). However,
      its exact functions during the tendon repair process still remain elusive. Here,
      we established an Achilles tendon injury model in a Tnmd knockout (Tnmd-/-) mouse
      line. Detailed analyses showed not only a very different scar organization with a
      clearly reduced cell proliferation and expression of certain tendon-related
      genes, but also increased cell apoptosis, adipocyte and blood vessel accumulation
      in the early phase of tendon healing compared with their wild-type (WT)
      littermates. In addition, Tnmd-/- tendon scar tissue contained augmented matrix
      deposition of biglycan, cartilage oligomeric matrix protein (Comp) and
      fibronectin, altered macrophage profile and reduced numbers of CD146-positive
      cells. In vitro analysis revealed that Tnmd-/- TSPCs exhibited significantly
      reduced migration and proliferation potential compared with that of WT TSPCs.
      Furthermore, Tnmd-/- TSPCs had accelerated adipogenic differentiation accompanied
      with significantly increased peroxisome proliferator-activated receptor gamma
      (Ppargamma) and lipoprotein lipase (Lpl) mRNA levels. Thus, our results
      demonstrate that Tnmd is required for prevention of adipocyte accumulation and
      fibrovascular scar formation during early tendon healing.

PMID- 29022914
TI  - Emergence of aspirin as a promising chemopreventive and chemotherapeutic agent
      for liver cancer.

PMID- 29022913
TI  - MBD2 upregulates miR-301a-5p to induce kidney cell apoptosis during vancomycin
      induced AKI.
AB  - Despite DNA methylation occurred in acute kidney injury (AKI), how it influenced
      progression of AKI remains unclear. Methyl-CpG-binding domain protein 2 (MBD2), a
      protein readers of methylation, was used to analyze the impact of DNA methylation
      on vancomycin (VAN)-induced AKI. Here, in cultured human kidney tubular
      epithelial cells (HK-2), we show that knockdown of MBD2 by siRNA attenuated VAN
      induced apoptosis, caspase activity, and the expression of BAX and cleaved
      caspase 3. Interestingly, knockdown of MBD2 by siRNA was associated with the
      suppression of miR-301a-5p. Mechanistic studies confirmed MBD2 binds to these
      methylated CpG elements of miR-301a-5p promoter, and then activates miR-301a-5p
      promoter by suppressing methylation. Furthermore, anti-miR-301a-5p significantly
      blocked VAN-induced apoptosis and caspase activity in HK-2 cells, which was
      accompanied by downregulation of p53, and upregulation of MITF, HDGF and MDM-4
      together. The latter genes were further identified as target genes of miR-301a
      5p, and silencing of MDM-4 promoted p53 accumulation. In vivo, mice with MBD2
      knockout (MBD2-KO) were counteracted to VAN-induced AKI, indicated by the
      analysis of renal function, histology, apoptosis and inflammation. MBD2-KO also
      significantly suppressed the expression of miR-301a-5p, p53, BAX and cleaved
      caspase 3, and restored the expression of MDM-4, MITF and HDGF. Finally, in vivo
      inhibition of miR-301a-5p also ameliorated VAN-induced AKI. Together, these
      results show the novel MBD2/miR-301a-5p/MITF, HDGF and MDM-4/p53 pathway in VAN
      induced AKI.

PMID- 29022915
TI  - Wild-type and mutant p53 differentially modulate miR-124/iASPP feedback following
      pohotodynamic therapy in human colon cancer cell line.
AB  - Colorectal cancer (CRC) is a most common digestive system malignant tumor. p53
      mutation has essential role in cancers and is frequently observed in CRC and
      presents a huge challenge. p53 mutation has been reported to attenuate the
      inhibitory effect of photofrin-based photodynamic therapy (PDT). p53 mutation
      induced gain of function brings up the dysfunction of carcinogenic factors,
      including miRNAs. Our research found that PDT suppressed CRC cell viability,
      reduced the tumor size and prolonged the survival time, all of which could be
      attenuated by p53 mutation or deletion. After p53 mutation or deletion, several
      miRNA expression levels were downregulated, among which miR-124 was the most
      strongly downregulated, whereas iASPP expression was upregulated. p53 binds to
      the promoter of miR-124 to promote its expression and then inhibited iASPP
      expression, so as to amplify the inhibitory effect of PDT on wild-type p53 cells.
      In p53-mutant or -deleted cells, this binding no longer worked to promote miR-124
      expression, and iASPP expression increased, finally resulted in promoted CRC cell
      viability upon PDT. The interactive modulation among miR and iASPP in p53-mutant
      or -deleted cells may serve as a crucial pathway, which mediates therapy
      resistance when p53 is mutated or deleted, in the process of PDT treatment of
      CRC.

PMID- 29022916
TI  - Molecular motion regulates the activity of the Mitochondrial Serine Protease
      HtrA2.
AB  - HtrA2 (high-temperature requirement 2) is a human mitochondrial protease that has
      a role in apoptosis and Parkinson's disease. The structure of HtrA2 with an
      intact catalytic triad was determined, revealing a conformational change in the
      active site loops, involving mainly the regulatory LD loop, which resulted in
      burial of the catalytic serine relative to the previously reported structure of
      the proteolytically inactive mutant. Mutations in the loops surrounding the
      active site that significantly restricted their mobility, reduced proteolytic
      activity both in vitro and in cells, suggesting that regulation of HtrA2 activity
      cannot be explained by a simple transition to an activated conformational state
      with enhanced active site accessibility. Manipulation of solvent viscosity
      highlighted an unusual bi-phasic behavior of the enzymatic activity, which
      together with MD calculations supports the importance of motion in the regulation
      of the activity of HtrA2. HtrA2 is an unusually thermostable enzyme (TM=97.3 
      degrees C), a trait often associated with structural rigidity, not dynamic
      motion. We suggest that this thermostability functions to provide a stable
      scaffold for the observed loop motions, allowing them a relatively free
      conformational search within a rather restricted volume.

PMID- 29022917
TI  - Trehalose protects against cadmium-induced cytotoxicity in primary rat proximal
      tubular cells via inhibiting apoptosis and restoring autophagic flux.
AB  - Autophagy has an important renoprotective function and we recently found that
      autophagy inhibition is involved in cadmium (Cd)-induced nephrotoxicity. Here, we
      aimed to investigate the protective effect of trehalose (Tre), a novel autophagy
      activator, against Cd-induced cytotoxicity in primary rat proximal tubular (rPT)
      cells. First, data showed that Tre treatment significantly decreased Cd-induced
      apoptotic cell death of rPT cells via inhibiting caspase-dependent apoptotic
      pathway, evidenced by morphological analysis, flow cytometric and immunoblot
      assays. Also, administration with Tre protected rPT cells against Cd-induced
      lipid peroxidation. Inhibition of autophagic flux in Cd-exposed rPT cells was
      markedly restored by Tre administration, demonstrated by immunoblot analysis of
      autophagy marker proteins and GFP and RFP tandemly tagged LC3 method.
      Resultantly, Cd-induced autophagosome accumulation was obviously alleviated by
      Tre treatment. Meanwhile, blockage of autophagosome-lysosome fusion by Cd
      exposure was noticeably restored by Tre, which promoted the autophagic
      degradation in Cd-exposed rPT cells. Moreover, Tre treatment markedly recovered
      Cd-induced lysosomal alkalinization and impairment of lysosomal degradation
      capacity in rPT cells, demonstrating that Tre has the ability to restore Cd
      impaired lysosomal function. Collectively, these findings demonstrate that Tre
      treatment alleviates Cd-induced cytotoxicity in rPT cells by inhibiting apoptosis
      and restoring autophagic flux.

PMID- 29022918
TI  - Ligand-dependent EphA7 signaling inhibits prostate tumor growth and progression.
AB  - The downregulation of receptor tyrosine kinase EphA7 is frequent in epithelial
      cancers and linked to tumor progression. However, the detailed mechanism of EphA7
      mediated prostate tumor progression remains elusive. To test the role of EphA7
      receptor in prostate cancer (PCa) progression directly, we generated EphA7
      receptor variants that were either lacking the cytoplasmic domain or carrying a
      point mutation that inhibits its phosphorylation by site-directed mutagenesis.
      Overexpression of wild-type (WT) EphA7 in PCa cells resulted in decreased tumor
      volume and increased tumor apoptosis in primary tumors. In addition, ectopic
      expression of WT EphA7 both can delay PCa cell proliferation and could inhibit
      PCa cell migration and invasion. This protein can also induce PCa cell apoptosis
      that correlated with increasing the protein expression levels of Bax, elevating
      the caspase-3 activities, reducing the protein expression levels of Bcl-2 and
      facilitating the dephosphorylation of Akt, which is further increased by the
      stimulation of ephrinA5-Fc. However, expression of these EphA7 mutants in PCa
      cells has no effect in vivo and in vitro. The expression of EphA7 and ephrinA5
      was significantly decreased in PCa specimens compared with BPH tissues or paired
      normal tissues. Moreover, the phosphorylation of EphA7 was positively related
      with ephrinA5 expression in human prostate tissues. In sum, receptor
      phosphorylation of EphA7, at least in part, suppress PCa tumor malignancy through
      targeting PI3K/Akt signaling pathways.

PMID- 29022920
TI  - The lncRNA TUG1 modulates proliferation in trophoblast cells via epigenetic
      suppression of RND3.
AB  - Due to limited treatment options, pre-eclampsia (PE) is associated with fetal
      perinatal and maternal morbidity and mortality. During the causes of PE, failure
      of uterine spiral artery remodeling which might be related to functioning
      abnormally of trophoblast cells, result in the occurrence and progression of PE.
      Recently, abnormal expression of long non-coding RNAs (lncRNAs), as imperative
      regulators involved in human diseases progression (included PE), which has been
      indicated by increasing evidence. In this research, we found that TUG1, a lncRNA,
      was markedly reduced in placental samples from patients with PE. Loss-function
      assays indicated that knockdown TUG1 significantly affected cell proliferation,
      apoptosis, migration and network formation in vitro. RNA-seq revealed that TUG1
      could affect abundant genes, and then explore the function and regulatory
      mechanism of TUG1 in trophoblast cells. Furthermore, RNA immunoprecipitation and
      chromatin immunoprecipitation assays validated that TUG1 can epigenetically
      inhibit the level of RND3 through binding to EZH2, thus promoting PE development.
      Therefore, via illuminating the TUG1 mechanisms underlying PE development and
      progression, our findings might furnish a prospective therapeutic strategy for PE
      intervention.

PMID- 29022919
TI  - DCZ3301, a novel cytotoxic agent, inhibits proliferation in diffuse large B-cell
      lymphoma via the STAT3 pathway.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma in
      adults, characterized by a rapidly increasing painless mass. A novel compound,
      DCZ3301, was synthesized that exerted direct cytotoxicity against DLBCL cell
      lines. The effects of DCZ3301 on DLBCL cells in vitro and in vivo and the
      associated mechanisms were investigated. DCZ3301 inhibited the viability of DLBCL
      cell lines, even in the presence of protumorigenesis cytokines. Additionally, the
      compound induced apoptosis and cell cycle arrest at the G2/M phase by reducing
      mitochondrial membrane potential. DCZ3301 exerted an antitumor effect through
      modulation of Akt, extracellular signal-regulated kinases 1/2 (ERK1/2) and janus
      kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3)
      signaling pathways. Furthermore, DCZ3301 downregulates STAT3 phosphorylation by
      inhibiting Lck/Yes-related novel protein tyrosine kinase (Lyn) activation in
      DLBCL. A synergistic cytotoxic effect on DLBCL cells was observed upon
      combination of DCZ3301 with panobinostat. In vivo, intraperitoneal injection of
      xenograft mice with DCZ3301 resulted in reduced tumor volume. Our preliminary
      results collectively support the utility of the small-molecule inhibitor DCZ3301
      as an effective novel therapeutic option for DLBCL that requires further clinical
      evaluation.

PMID- 29022922
TI  - RANKL-mediated harmonious dialogue between fetus and mother guarantees smooth
      gestation by inducing decidual M2 macrophage polarization.
AB  - Decidual macrophages (dMphi) contribute to maternal-fetal tolerance. However, the
      mechanism of dMphi differentiation during pregnancy is still largely unknown.
      Here, we report that receptor activator for nuclear factor-kappa B ligand
      (RANKL), secreted by human embryonic trophoblasts and maternal decidual stromal
      cells (DSCs), polarizes dMphi toward a M2 phenotype. This polarization is
      mediated through activation of Akt/signal transducer and activator of
      transcription 6 (STAT6) signaling, which is associated with the upregulation of
      histone H3 lysine-27 demethylase Jmjd3 and IRF4 in dMphi. Such differentiated
      dMphi can induce a Th2 bias that promotes maternal-fetal tolerance. Impaired
      expression of RANKL leads to dysfunction of dMphi in vivo and increased rates of
      fetal loss in mice. Transfer of RANK+Mphi reverses mouse fetal loss induced by
      Mphi depletion. Compared with normal pregnancy, there are abnormally low levels
      of RANKL/RANK in villi and decidua from miscarriage patients. These results
      suggest that RANKL is a pivotal regulator of maternal-fetal tolerance by
      licensing dMphi to ensure a successful pregnancy outcome. This observation
      provides a scientific basis on which a potential therapeutic strategy can be
      targeted to prevent pregnancy loss.

PMID- 29022924
TI  - Listeriosis in pregnancy: under-diagnosis despite over-treatment.
AB  - OBJECTIVE: To compare the symptomatology of pregnant women with suspected
      listeriosis to culture confirmed listeriosis. STUDY DESIGN: All cases of
      suspected and culture confirmed pregnancy-associated listeriosis from a single
      center were retrospectively reviewed assessing demographics, clinical, laboratory
      and pathological findings, and maternal, fetal and neonatal outcomes. RESULTS:
      Listeriosis was identified in seven patients, none of whom belonged to the 117
      women with suspected listeriosis. Women with confirmed infection were more likely
      to exhibit fever (P=0.01), flu-like symptoms (P=0.006), threatened preterm labor
      (P=0.05) and inflammatory markers (P=0.02), but less likely to exhibit
      gastrointestinal complaints (P=0.004) in comparison with suspected non-confirmed
      cases. Confirmed cases resulted in preterm delivery (n=5) and stillbirth (n=2).
      Neonatal complications included meningitis, respiratory disease and sepsis.
      Maternal outcomes were favorable. CONCLUSION: Although 'febrile gastroenteritis'
      is a poor predictor of listeriosis in pregnancy, fever, premature contractions
      and inflammatory markers are important risk indices prompting workup and adequate
      empiric treatment.

PMID- 29022921
TI  - Current progress in the derivation and therapeutic application of neural stem
      cells.
AB  - Neural stem cells (NSCs) have a unique role in neural regeneration. Cell therapy
      based on NSC transplantation is a promising tool for the treatment of nervous
      system diseases. However, there are still many issues and controversies
      associated with the derivation and therapeutic application of these cells. In
      this review, we summarize the different sources of NSCs and their derivation
      methods, including direct isolation from primary tissues, differentiation from
      pluripotent stem cells and transdifferentiation from somatic cells. We also
      review the current progress in NSC implantation for the treatment of various
      neural defects and injuries in animal models and clinical trials. Finally, we
      discuss potential optimization strategies for NSC derivation and propose urgent
      challenges to the clinical translation of NSC-based therapies in the near future.

PMID- 29022923
TI  - Gadd45a opens up the promoter regions of miR-295 facilitating pluripotency
      induction.
AB  - MicroRNAs (miRNAs) play crucial roles in the establishment of pluripotent state
      by controlling pluripotent network. However, the molecular mechanisms controlling
      miRNAs during somatic cell reprogramming remain obscure. In this study, we show
      Gadd45a (growth arrest and DNA-damage-inducible protein 45a) enhances
      reprogramming by activating miR-295. Furthermore, we show that Gadd45a binds the
      promoter regions of miR-295. Nuclease accessibility assay indicates that Gadd45a
      opens the promoter regions of miR-295. Levels of H3K9Ac and H3K27Ac on the
      promoter regions of miR-295 were also increased. In conclusion, our results
      indicate that Gadd45a relaxes the promoter regions of miR-295 and promotes the
      expression of miR-295 during reprogramming, implying a concise mechanism of
      Gadd45a and miR-290 cluster cooperation in cell-fate determination.

PMID- 29022926
TI  - Erratum: Transmembrane TNF-alpha Density, But Not Soluble TNF-alpha Level, is
      Associated with Primary Response to Infliximab in Inflammatory Bowel Disease.
AB  - This corrects the article DOI: 10.1038/ctg.2017.44.

PMID- 29022925
TI  - Anti-cytomegalovirus immunoglobulin M titer for congenital infection in first
      trimester pregnancy with primary infection: a multicenter prospective cohort
      study.
AB  - OBJECTIVE: We evaluated cytomegalovirus (CMV) immunoglobulin M (IgM) titer in
      pregnant women with primary infection as a predictive factor for congenital
      infection. STUDY DESIGN: Maternal CMV antibody screening during the first
      trimester was conducted prospectively at 16 centers in Japan between September
      2013 and 2015. Women with confirmed maternal primary infection underwent testing
      for fetal congenital infection, and we investigated the positive predictive value
      of CMV IgM titer levels for congenital infection in women with a low IgG avidity.
      RESULTS: We identified 6 (8.6%) cases of congenital infection among 70 pregnant
      women with positive/borderline IgG, positive IgM and IgG avidity index ?35.0% and
      11 (39.3%) among 28 women with IgG and/or IgM seroconversion. IgM titer level
      ?6.00 index showed the highest positive predictive value (17.1%). CONCLUSION:
      High titer of CMV IgM during the first trimester in pregnant women with primary
      infection is a risk factor for congenital infection.

PMID- 29022927
TI  - How the United States plans to trap its biggest stash of nuclear-weapons waste in
      glass.

PMID- 29022928
TI  - Climate meetings pose serious test in the Trump era.

PMID- 29022929
TI  - Navajo Nation reconsiders ban on genetic research.

PMID- 29022930
TI  - The ambitious effort to document California's changing deserts.

PMID- 29022932
TI  - A more personal view of human-gene regulation.

PMID- 29022931
TI  - The future of DNA sequencing.

PMID- 29022933
TI  - The rise and fall and rise again of 23andMe.

PMID- 29022935
TI  - ResearchGate lawsuit, walrus spat and a Second World War shipwreck.

PMID- 29022934
TI  - Marine snow falls heaviest at the Equator.

PMID- 29022936
TI  - Scientists plead with Brazilian government to restore funding.

PMID- 29022938
TI  - Build on the outer space treaty.

PMID- 29022937
TI  - Cryo-electron microscopy wins chemistry Nobel.

PMID- 29022939
TI  - Developing nations need more than just money.

PMID- 29022940
TI  - Gene-expression study raises thorny ethical issues.

PMID- 29022941
TI  - Genome-wide mapping of DNase I hypersensitive sites in rare cell populations
      using single-cell DNase sequencing.
AB  - Increased chromatin accessibility is a feature of cell-type-specific cis
      regulatory elements; therefore, mapping of DNase I hypersensitive sites (DHSs)
      enables the detection of active regulatory elements of transcription, including
      promoters, enhancers, insulators and locus-control regions. Single-cell DNase
      sequencing (scDNase-seq) is a method of detecting genome-wide DHSs when starting
      with either single cells or <1,000 cells from primary cell sources. This
      technique enables genome-wide mapping of hypersensitive sites in a wide range of
      cell populations that cannot be analyzed using conventional DNase I sequencing
      because of the requirement for millions of starting cells. Fresh cells,
      formaldehyde-cross-linked cells or cells recovered from formalin-fixed paraffin
      embedded (FFPE) tissue slides are suitable for scDNase-seq assays. To generate
      scDNase-seq libraries, cells are lysed and then digested with DNase I. Circular
      carrier plasmid DNA is included during subsequent DNA purification and library
      preparation steps to prevent loss of the small quantity of DHS DNA. Libraries are
      generated for high-throughput sequencing on the Illumina platform using standard
      methods. Preparation of scDNase-seq libraries requires only 2 d. The materials
      and molecular biology techniques described in this protocol should be accessible
      to any general molecular biology laboratory. Processing of high-throughput
      sequencing data requires basic bioinformatics skills and uses publicly available
      bioinformatics software.

PMID- 29022942
TI  - Facile synthesis of gold nanomaterials with unusual crystal structures.
AB  - Gold (Au) nanomaterials have attracted wide research attention, owing to their
      high chemical stability, promising catalytic properties, excellent
      biocompatibility, unique electronic structure and outstanding localized surface
      plasmon resonance (LSPR) absorption properties; all of which are closely related
      to their size and shape. Recently, crystal-phase-controlled synthesis of noble
      metal nanomaterials has emerged as a promising strategy to tune their
      physicochemical properties. This protocol describes the detailed experimental
      procedures for the crystal-phase-controlled syntheses of Au nanomaterials with
      unusual crystal structures under mild conditions. Briefly, pure hexagonal close
      packed (hcp) Au square sheets (AuSSs) with a thickness of ~2.4 nm are synthesized
      using a graphene-oxide-assisted method in which HAuCl4 is reduced by oleylamine
      in a mixture of hexane and ethanol. By using pure hexane as the solvent, well
      dispersed ultrathin hcp/face-centered cubic (fcc) Au nanowires with a diameter of
      ~1.6 nm on graphene oxide can be obtained. Meanwhile, hcp/fcc Au square-like
      plates with a side length of 200-400 nm are prepared via the secondary growth of
      Au on the hcp AuSSs. Remarkably, hexagonal (4H) Au nanoribbons with a thickness
      of 2.0-6.0 nm can be synthesized with a one-pot colloidal method in which HAuCl4
      is reduced by oleylamine in a mixed solvent of hexane and 1,2-dichloropropane. It
      takes 17-37 h for the synthesis of these Au nanomaterials with unusual crystal
      structures. Transmission electron microscopy (TEM) and atomic force microscopy
      (AFM) are used to characterize the resultant Au nanomaterials, which could have
      many promising applications, such as biosensing, near-IR photothermal therapy,
      catalysis and surface-enhanced Raman scattering (SERS).

PMID- 29022948
TI  - Retinoblastoma: An overview of modern management.
AB  - Retinoblastoma (RB) is an embryonic tumor originating from the retinal cells. RB
      is the most common intraocular cancer of childhood and accounts for 4% of all
      pediatric malignancies.

PMID- 29022944
TI  - Erratum: Strains, functions and dynamics in the expanded Human Microbiome
      Project.
AB  - This corrects the article DOI: 10.1038/nature23889.

PMID- 29022943
TI  - Simultaneous measurement of sleep and feeding in individual Drosophila.
AB  - Drosophila is widely used for the dissection of genetic and neuronal mechanisms
      of behavior. Recently, flies have emerged as a model for investigating the
      regulation of feeding and sleep. Although typically studied in isolation,
      increasing evidence points to a fundamental connection between these behaviors.
      Thus, a system for measuring sleep and feeding simultaneously in a single
      integrated system is important for interpreting behavioral shifts of either
      state. Here, we describe the construction and use of the Activity Recording
      Capillary Feeder or CAFE (ARC), a machine-vision (automated image tracking)-based
      system for the integrated measurement of sleep and feeding in individual
      Drosophila. Flies feed on liquid food from a microcapillary, and consumption is
      measured by tracking the liquid meniscus over time. Sleep measurements are
      obtained from positional tracking of individual animals, and arousal threshold
      can be determined by vibrational stimulus response. Using this system, a single
      computer and experimenter can track diverse behaviors from up to 60 individual
      flies in a single integrated system. The ARC is efficiently assembled with
      minimal training, and each experiment can be run for up to ~7 d, with a total
      setup and breakdown time of ~2 h.

PMID- 29022949
TI  - SHAPU: Forty years on Mystery Persists.
AB  - In 1975, our team encountered several cases of severe inflammatory eye disease
      presenting as a white pupil in a red eye with rapid loss of vision. The eyes
      became soft within a few days with shallow anterior chamber which we called
      "Malignant Hypotension" in view of the latter's sinister significance.
      Unilaterally, little or no pain, predominantly affecting children and difficulty
      in dilating the pupil and keeping it dilated were some of the other important
      features. Posterior segment was not visible due to massive exudation in vitreous.
      Microbiological investigations of aqueous humor did not retrieve any bacterial or
      fungal organisms. All eyes became pthisical in few weeks despite treatment with
      topical and subconjunctival antibiotics and steroids. Similar cases appeared
      again after two years in 1977 with identical presentation and outcome. Both out
      breaks began during September and lasted until about January- the next year.

PMID- 29022950
TI  - Diabetes Mellitus and the risk of Primary open angle glaucoma.
AB  - BACKGROUND: Diabetes mellitus (DM) is one of the risk factors for Primary open
      angle glaucoma (POAG). Inclusion of DM as a risk factor for POAG is
      controversial. The objectives of the study were to investigate whether Type II
      (T2) DM is a risk factor for POAG and to determine central corneal thickness
      (CCT) in the subjects with T2DM and to examine the relationship between T2DM and
      intraocular pressure (IOP). MATERIALS AND METHODS: A comparative cross sectional
      study was conducted including 189 subjects of age > 40 years. In Group I, 113
      patients diagnosed with T2DM and Group II, age and sex matched 76 subjects with
      POAG without DM was included. Detailed ocular examination, IOP, CCT and
      funduscopy evaluation was done. RESULTS: Most of the patients were more than 60
      years of age with mean age 58 +/- 11 years. Male: female ratio was 1:1. POAG was
      seen in 27.4% of patients with T2DM. Mean IOP in T2DM was 14.67+/- 2.63mmHg and
      in non diabetic, 17.25+/-4.47 mmHg (p less than0.00). In group I, mean CCT was
      538.83+/- 22.7MUm and in group II, 531.26 +/- 20.9MUm (p-0.126). There was no
      association between CCT and glaucoma (p=0.072, 95% CI: -0.76 -17.46). The study
      could not elicit an association of T2DM with glaucoma. Duration of T2DM did not
      affect an association between T2DM and glaucoma (p-0.757). Random blood sugar (p
      less than0.001) and oral hypoglycemic drugs (p=0.030) showed an association with
      glaucoma. CONCLUSION: The study failed to show an association between T2DM and
      primary open angle glaucoma and CCT though an association seen with IOP. A larger
      prospective comparative study may be help in understanding this association.

PMID- 29022951
TI  - Safety of Fixed drug Combination in Post -Operative Cataract Patients, at
      Tertiary Care Centre - In South India.
AB  - INTRODUCTION: Cataract is any opacification in lens or its capsule, which
      accounts for about 50% of treatable blindness worldwide. The prevalence of
      cataract in India is about 62.6%. The incidence of post operative endophthalmitis
      ranges from 0.05% - 0.14% and so the use of post-operative antibiotics and
      steroids is necessary to control infection and prevent inflammation. Fixed drug
      combinations not only cut the cost but also the dosage and improve the compliance
      of patients in the immediate post operative period. In this regard, the present
      study was conducted with the aim of studying the efficacy of using fixed drug
      combination (Difluprednate and Moxifloxacin) in reducing ocular inflammation and
      pain in post-operative patients undergoing cataract surgery. METHODOLOGY: Study
      design: Prospective interventional study, in which 749 eyes underwent SICS with
      IOL. All of them were treated with Difluprednate and Moxifloxacin, combination
      eye drops postoperatively 4 times a day, and reviewed on day 1, 5 and once in two
      weeks up to 6 weeks. RESULTS: Out of 749 eyes, 730 were normal, 10 eyes had
      minimal raise in IOP in the range of 21 mmHg-31mmHg (considering 21mmHg as
      baseline) which decreased without any intervention within 3 weeks and only 9 eyes
      had raise in IOP of more than 31mmHg, which did not decrease in spite of
      discontinuing the drops and needed anti-glaucoma treatment. CONCLUSION: Our study
      clearly shows that fixed drug combination of antibiotic and steroid does not
      cause raised IOP in about 97% of cases of SICS in the post-operative period and
      also improves the compliance of the patients.

PMID- 29022952
TI  - Ocular morbidity among porters at high altitudes.
AB  - INTRODUCTION: High altitude, often characterized by settings over 2400m, can be
      detrimental to the human body and pose a significant risk to ocular health.
      Reports concerning various ocular morbidities occurring as a consequence of high
      altitude are limited in the current literature. OBJECTIVES: This study was aimed
      at evaluating the ocular health of porters working at high altitudesof Himalayas
      in Nepal. MATERIALS AND METHODS: A mobile eye clinic was set up in Ghat and
      patient data were collected from its out- patient unit by a team of seven
      optometrists which was run for five days. Ghat is a small village in north
      eastern Nepal, located at 2860 m altitude. Travellers walking through the
      trekking route were invited to get their eyes checked at the clinic.
      Comprehensive ocular examinations were performed, including visual acuities,
      objective and subjective refraction, anterior and posterior segment evaluations,
      and intraocular pressure measurements; blood pressure and blood glucose levels
      were also measured as required. Ocular therapeutics, prescription glasses,
      sunglasses and ocular health referrals were provided free of cost as necessary. A
      total of 1890 people visited the eye clinic, among which 57.4% (n=1084) were
      porters. CONCLUSIONS: Almost half of the porters had an ocular morbidity.
      Correctable refractive error was most prevalent, with other ocular health-related
      complications, including dry eye disease, infectious disorders, glaucoma and
      cataract. Proper provision of regular and effective eye care services should be
      made more available for those residing at these high altitudes in Nepal.

PMID- 29022953
TI  - Pattern of Corneal Diseases in Paediatric Age Group at a Tertiary Eye Care Center
      in Nepal.
AB  - OBJECTIVE: It is to study the pattern of corneal diseases (including injuries) in
      paediatric population in a tertiary eye care center. MATERIALS AND METHODS: A
      descriptive, cross sectional study was carried out in a tertiary eye care center
      which included 176 cases. RESULTS: Out of 176 cases studied, 6 cases (3.4%)
      presented with congenital causes, 4 cases (2.27%) were of dystrophy and ectasia,
      63 cases (35.79%) had infective origin, 17 cases (9.65%) had inflammatory cause,
      9 cases (5.11%) had systemic association and 77 cases (43.75%) had traumatic
      causes. CONCLUSION: Trauma was noted to be the most important cause for corneal
      diseases in paediatric population followed by infective conditions. Viral
      keratitis was found to be the most common type of corneal infection in the
      paediatric age group.

PMID- 29022954
TI  - Agreement on diabetic retinopathy grading in fundus photographs by allied
      ophthalmic personnel as compared to ophthalmologist at a community setting in
      Nepal.
AB  - INTRODUCTION: Diabetic retinopathy (DR) is the emerging cause of blindness in the
      developing world. Timely detection of DR could save vision from its avoidable
      blinding condition. OBJECTIVE: To assess the accuracy of DR grading in fundus
      photographs by the allied ophthalmic personnel (AOP) as compared to
      ophthalmologist at a community setting in Nepal. MATERIALS AND METHODS: Fundus
      photographs of known diabetes subjects attending for DR screening were graded by
      two groups of AOP and ophthalmologist. Agreement for DR grading by the AOP versus
      ophthalmologist was assessed using kappa coefficient (k). RESULTS: Fundus
      photographs of 864 eyes of 435 subjects with diabetes were evaluated in the
      study. The agreement was substantial for detection of normal versus abnormal
      retina by both the AOP 1 and AOP 2. For normal versus abnormal macula, the
      agreement was substantial for AOP 1 and moderate for AOP 2. The agreement for
      grading macular exudates, retinal hemorrhage, venous beading ranged from moderate
      to substantial for both the AOPs. There was overall substantial agreement for
      diagnosing cases with or without DR and CSME by both the AOP 1 and AOP 2. The
      agreement ranged from fair to moderate for diagnosing other stages of NPDR by
      both the AOPs. CONCLUSION: Allied ophthalmic personnel with training could be a
      first level DR screener and referral of vision threatening DR. Three out of five
      diabetics could be managed at community level and thus reduce work load of
      ophthalmologist. This DR screening modality can be useful in other resource
      limited countries.

PMID- 29022955
TI  - Demographic pattern and clinical characteristics of optic neuritis in a tertiary
      eye care centre.
AB  - PURPOSE: To study the demographic pattern and clinical characteristics of optic
      neuritis cases in a tertiary eye care centre in Nepal. DESIGN: Descriptive, cross
      sectional study. METHODOLOGY: Complete ocular examination was done in all the
      newly diagnosed cases of optic neuritis presenting from January 1st 2012 to June
      30th 2013. Demographic pattern, clinical features, visual acuity, colour vision,
      contrast sensitivity and visual field defects were studied. RESULTS: Sixty seven
      eyes of 50 patients (28 females and 22 males) with optic neuritis were included
      in the study. The mean age was 34.32 years +/- 13.72 years. The male: female
      ratio was 1:1.27. All the cases presented with complaint of blurring of vision.
      Painful ocular movement was noted in 58%. On ophthalmoscopic examination around
      2/3rd of eyes suffered from papillitis (72%) and 1/3rd from retrobulbar optic
      neuritis (27%). Only one case of neuroretinitis (1%) was seen in the study. The
      colour vision pattern was variable. Contrast sensitivity was reduced in 94%.
      Centrocaecal scotoma was seen in 10.5%. CONCLUSION: Females were predominantly
      affected. Unilateral involvement was the most common presenting as papillitis.

PMID- 29022956
TI  - Ultrasound evaluation of normal orbital preseptal thickness.
AB  - INTRODUCTION: Orbital preseptal thickness is an important parameter not only in
      diagnosis of orbital cellulitis but also in recent classification and management
      of dark eye circle (DEC). OBJECTIVE: The aim of this study was to evaluate normal
      preseptal thickness and collect baseline data in normal skin in a given
      population with no orbital pathology. MATERIALS & METHOD: Ultrasound was
      performed on 42 patients (23 females and 19 males) with clinically normal eyes
      and orbits for evaluation of normal orbital preseptal thickness. The age ranged
      between 15 to 35 years with a mean age of 24.9 years. RESULTS: Our study
      concluded that normal preseptal thickness ranged from 2.1 mm to 5.5 mm. Mean
      preseptal thickness for both sides was 3.9 mm. CONCLUSION: Ultrasound can be used
      as quick, reliable and cost-effective modality for evaluation of orbital
      preseptal thickness.

PMID- 29022957
TI  - Clinical Patterns and risk factors for rhegmatogenous retinal detachment at a
      tertiary eye care centre of northern India.
AB  - PURPOSE: To identify patterns and risk factors for rhegmatogenous retinal
      detachment (RD) in northern India. METHODS: This was a retrospective study
      conducted at a tertiary care centre in northern India. 378 consecutive records of
      patient, operated between January 2011 to June 2012 were included for analysis.
      Clinical history, signs and risk factors of RD were evaluated. Comparison was
      done with available literature from other developing nations. RESULTS: Mean age
      of the patients was 40.12 + 20.43 years (Range 12-85 years); 81% were male and
      half of the patients presented after 1 month of visual symptoms. Retinal breaks
      were discovered commonly in the temporal region, while no break was found in10%
      of the patients. PVR more than grade C was seen in a third of the patients. Prior
      surgery for cataract was found to be the most common identifiable risk factor for
      RD (40%). Bilateral RD was seen in 13% of the patients. CONCLUSION: Pseudophakia
      is the commonest risk factor for RD. If no retinal break is discovered pre
      operatively, the surgeon should seek a retinal break temporally during surgery.
      Bilateral RD is a serious concern for rural northern India, probably linked to
      delayed presentation.

PMID- 29022958
TI  - Unilateral lattice corneal dystrophy in a young female: A unique case report.
AB  - BACKGROUND: Unilateral lattice corneal dystrophy is a rare entity. OBJECTIVE: To
      highlight the evidence of unilateral lattice corneal dystrophy in a young female.
      CASE: A young 28 years old female presented to the outpatient department of
      Ophthalmology with slowly progressive diminution of vision in left eye for one
      month. On ophthalmological examination best corrected visual acuity (BCVA) was
      20/20 and 20/40 with refractive error of plano and -0.75D Cyl @30 for right and
      left eye respectively. Ocular examination of right eye was unremarkable. On slit
      lamp examination, left eye showed multiple radial lattice lines in branching
      spider like pattern in the temporal cornea with pupillary margin involvement. The
      lattice pattern was confined to anterior to midstroma of the cornea with intact
      epithelium and unremarkable endothelium. The lesions did not involve the limbus.
      These lattice lines were prominent on retroillumination. In temporal quadrant
      near pupillary margin a small radial nebulomacular corneal opacity was seen
      without any corneal vascularisation or edema. The anterior chamber was deep and
      quiet. Corneal sensations were markedly reduced. Intraocular pressure was 10 and
      12mmHg for right and left eye respectively with noncontact tonometry. Fundus
      examination was unremarkable. Family history and systemic history was negative.
      Optical coherence tomography(OCT) showed hyperreflective material in midstoma
      confirmed the diagnosis of unilateral lattice corneal dystrophy(LCD) with an
      apparently healthy fellow eye.

PMID- 29022959
TI  - Alveolar soft part sarcoma of the orbit, a case report of a rare tumor.
AB  - BACKGROUND: Alveolar Soft Part Sarcoma is a rare malignant tumor of uncertain
      histogenesis, representing 0.5-1% of all soft tissue tumors. It occurs
      predominantly in head and neck regions, especially the orbit and the tongue, in
      infants, causing no specific symptoms for an extended period of time. CASE: A
      four year old girl was brought to consultation because of persistent swelling of
      her left upper and lower eyelid for the past six months. A 4 mm proptosis was
      noted on her left eye with significant upwards displacement of the globe. A firm,
      not pulsating and non tender mass was palpated, and motility examination revealed
      deficient abduction and infraduction. Visual acuity was 20/40 and 1/200 in the
      right and left eye, respectively. The computed tomography revealed an extraconal
      mass on the inferotemporal aspect of the left orbit, with no bony erosion or
      globe invasion. An excisional biopsy was made, finding a tumor with nests of
      clusters of large polygonal cells, separated by fibrous septa and a sinusoidal
      vascular channel. An Alveolar Soft Part Sarcoma was diagnosed. Our patient had a
      favorable post-operative follow up, and oncologic evaluations have not shown
      metastasis or local recurrences. Observations and Conclusions: Alveolar Soft Part
      Sarcoma is a rare malignant tumor of indolent course, but with propensity to
      distant metastases, making early diagnose and long term follow up necessary.

PMID- 29022960
TI  - Idiopathic Intracranial Hypertension in a pubertal paediatric Indian patient.
AB  - BACKGROUND: Idiopathic Intracranial Hypertension (IIH) is characterised by raised
      intracranial pressure (ICP) with normal cerebrospinal fluid (CSF) composition and
      absence of hydrocephalus or space occupying lesions. IIH is a rare disease in
      children. It can lead to visual impairment but prompt diagnosis and treatment in
      most of the cases will prevent potentially permanent visual loss. OBJECTIVE: To
      report a rare case of Idiopathic Intracranial Hypertension in a pubertal child,
      clinical features, and findings of Magnetic Resonance Imaging (MRI) and visual
      field of this case. CASE: An adolescent girl aged 14 years presented with
      headache and transient visual obscuration for two weeks. On examination, findings
      (fundus, visual field and MRI) were suggestive of Idiopathic intracranial
      hypertension. She did not have any classical predisposing risk factors. She
      recovered very well with acetazolamide and short term steroid therapy with no
      sequelae and clinical recurrence over a follow up of 12 months. CONCLUSION: This
      is a rare case of IIH in a child, which was confirmed on the MRI and visual field
      testing.

PMID- 29022961
TI  - Orbital Teratoma: A rare congenital tumour.
AB  - BACKGROUND: Orbital teratomas are congenital, unilateral germ cell tumors, which
      are present at birth with moderate to massive proptosis. The rare tumour has to
      be managed individually and is at times difficult. CASE: A female child in her
      2nd day of life was brought to our department with complains of forward bulging
      of the left eye which was noticed since the time of her birth. OBSERVATION:
      Examination and investigations revealed a mass with scattered foci of
      calcification. The mass was causing expansion of left orbit with thinning and
      scalloping of bony boundaries of left orbit with no intracranial component. The
      scan suggests the diagnosis of orbital teratoma which was further confirmed by
      histopathological examination. CONCLUSION: The rare tumour presents a challenge
      in management. The aim of management depends upon the extent of tumour,
      preservation of vision whenever possible, promotion of normal orbital growth and
      cosmesis.

PMID- 29022962
TI  - Retinal necrosis as the initial presentation of primary intraocular lymphoma.
AB  - A 72 years old female presented with bilateral painless progressive loss of
      vision over one year. She was diagnosed as non-resolving bilateral panuveitis.
      Her visual acuity in right eye was hand movement close to face and left eye was
      perception of light with inaccurate projection of rays. Bilateral anterior
      chamber had 1+ cells and flares. Vitreous cells had 1+ cells and haze in right
      eye but the left eye had 3+ vitreous cells and haze. Right eye fundus had
      multiple, discrete sub retinal yellowish deposits with subretinal haemorrhage and
      macular edema with perivascular infiltrates. In left eye, disc was just visible.
      The patient underwent diagnostic vitrectomy in left eye and undiluted vitreous
      sample on cytology showed reactive large lymphoid cells with necrotic background
      pattern suggestive of intraocular lymphoma. Patient underwent external beam
      radiotherapy and chemotherapy.

PMID- 29022963
TI  - Tuberculous Osteomyelitis of Orbit- A Case Report.
AB  - BACKGROUND: Orbital tuberculosis is a rare manifestation of extrapulmonary
      tuberculosis. We report an interesting case of osteomyelitis of orbital bone in
      an Indian child. CASE REPORT: A 9- year old girl presented with a gradually
      increasing painless swelling of left upper lid and blepharoptosis along with
      swelling of left side of forehead for last two months. The swelling was soft,
      fluctuating and non-tender. Diagnostic tap revealed thick pus which prompted us
      to do an incisional drainage of the abscess. The pus was sterile on
      microbiological examination. A diagnosis of osteomyelitis of orbit along with
      cold abscess of infratemporal fossa was made on the basis of clinical
      examination, positive Mantoux (MX) test, high erythrocyte sedimentation rate
      (ESR) and bony erosion of frontal and zygomatic bones in contrast enhanced
      computerized tomography (CECT). Patient showed marked improvement with
      antitubercular drug (ATD) but a sinus developed at the incision site. Six months
      later patient presented with occasional serous discharge from the sinus.The
      patient underwent excision of the sinus along with curettage and debridement of
      the left frontal bone and the tissue was sent for histopathological and
      microbiological examination. ATD was continued for 15 months. Her post-treatment
      three year follow up was without any recurrence. CONCLUSION: High index of
      suspicion should be kept for early diagnosis and timely treatment of the orbital
      tuberculosis. We want to report the case because of its rarity and clinical
      interest.

PMID- 29022964
TI  - Nocardia Arthritidis Keratitis: Case Report and Review of the Literature.
AB  - INTRODUCTION: Keratitis due to Nocardia infection is not commonly encountered in
      clinical practice and may therefore be mistaken for fungal or viral keratitis
      leading to delayed treatment and increased risk of permanent visual impairment.
      CASE: An otherwise healthy 27 years old Caucasian Active Duty military member
      presented to the clinic with three days of light sensitivity and irritation of
      his right eye. He carried a history of PRK in both eyes six years prior and
      admitted to recent contact lens overuse. With empiric treatment for typical
      bacterial keratitis including corticosteroids, his condition worsened on close
      follow-up. While awaiting cultures, a shift to fortified topical antibiotics
      tobramycin, moxifloxacin and ciprofloxacin showed improvement with closure of the
      epithelial defect. Ulcerative relapse occurred with withdrawal of therapy.
      Culture proven Nocardia arthritidis prompted successful treatment with topical
      antibiotic amikacin. On follow-up at three months, the patient was doing well
      with a small peripheral anterior stromal scar without permanent visual sequelae.
      Visual acuity returned to baseline of 20/20 in the affected eye. CONCLUSION:
      Keratitis caused by Nocardia species, including arthritidis, responds well to
      amikacin. Late diagnosis and early treatment withdrawal may lead to a prolonged
      recovery. Current literature indicates that corticosteroids may be harmful in the
      treatment of Nocardia keratitis. Increased awareness of Nocardia as an ocular
      pathogen has the potential to reduce unnecessary morbidity related to delayed
      diagnosis, inadequate therapy and inappropriate use of corticosteroids.

PMID- 29022965
TI  - A rare presentation of exudative macroaneurysms in unilateral Eales' disease.
AB  - BACKGROUND: A case of exudative macroaneurysms in unilateral Eales' disease is
      reported. 'Eales disease' is an idiopathic bilateral occlusive periphlebitis with
      neovascularisation and mostly presents with vitreous hemorrhage. CASE: A 30 year
      old male presented with diminution of vision in left eye (6/36) for 1 month. Slit
      Lamp examination of both eyes revealed normal anterior segment. Fundus
      examination of left eye with + 90 D lens revealed reddish lesions at the macula
      with surrounding circinate exudation. On peripheral examination hemorrhages were
      seen along with vasculitis in the superotemporal quadrant.The right eye fundus
      was normal.All laboratory investigations were found within normal limits.
      CONCLUSION: Eales' disease is mostly a bilateral condition but this case is rare
      as there is uniocular involvement with exudative macroaneurysms.Laser therapy was
      instituted which was effective in management of this condition with restoration
      of normal visual acuity.There was no relapse on follow up for 2 years.

PMID- 29022966
TI  - Thermo-responsive self-immolative nanoassemblies: direct and indirect triggering.
AB  - A thermo-responsive end-cap based on a retro-Diels-Alder and subsequent furan
      elimination reaction was developed. It was used to cap poly(ethyl glyoxylate),
      allowing end-to-end depolymerization upon thermal triggering. Using block
      copolymers, thermo-responsive micelles and vesicles were prepared and shown to
      disassemble upon heating. Thermal degradation could also be triggered indirectly
      by magnetic field hyperthermia after incorporation of iron oxide nanoparticles
      into the assemblies.

PMID- 29022967
TI  - Aza-capped cyclodextrins for intra-cavity metal complexation.
AB  - Aza-capped, methylated cyclodextrins (CDs) were obtained in high yields by
      reacting the soft nitrogen nucleophile 2-nitrobenzenesulfonamide with either A,B
      dimesylated CDs in basic media or their diol analogues under Mitsunobu reaction
      conditions followed by deprotection with thiophenol. A methyl pyridine
      substituent was grafted on the N atom of these secondary amines. When built on an
      alpha-CD scaffold, the resulting tertiary amine no longer undergoes nitrogen
      inversion at room temperature and behaves as a confining ligand, opening the way
      to intra-cavity metal complexation and promoting the formation of supramolecular
      helices.

PMID- 29022968
TI  - The structure of coronene cluster ions inferred from H2 uptake in the gas phase.
AB  - Mass spectra of helium nanodroplets doped with H2 and coronene feature anomalies
      in the ion abundance that reveal anomalies in the energetics of adsorption sites.
      The coronene monomer ion strongly adsorbs up to n = 38 H2 molecules indicating a
      commensurate solvation shell that preserves the D6h symmetry of the substrate. No
      such feature is seen in the abundance of the coronene dimer through tetramer
      complexed with H2; this observation rules out a vertical columnar structure.
      Instead we see evidence for a columnar structure in which adjacent coronenes are
      displaced in parallel, forming terraces that offer additional strong adsorption
      sites. The experimental value for the number of adsorption sites per terrace,
      approximately six, barely depends on the number of coronene molecules. The
      displacement estimated from this number exceeds the value reported in several
      theoretical studies of the bare, neutral coronene dimer.

PMID- 29022969
TI  - Syntheses, structures and properties of metal phosphates Pb2Mg(PO4)2,
      Pb4Zn8(PO4)8 and alpha-BaZn2(PO4)2.
AB  - Pb2Mg(PO4)2, Pb4Zn8(PO4)8 and alpha-BaZn2(PO4)2 have been synthesized by the
      standard solid-state reaction and their structures were determined by single
      crystal X-ray diffraction for the first time. Pb2Mg(PO4)2, Pb4Zn8(PO4)8 and alpha
      BaZn2(PO4)2 crystallize in the monoclinic crystal system, P21/c, C2/c and the
      trigonal crystal system, P3[combining macron]m1, respectively. The structure of
      Pb2Mg(PO4)2 possesses a three-dimensional framework consisting of MgO6 octahedra
      and PO4 tetrahedra and the Pb2+ cations reside in the [Mg6P6O12] tunnels.
      Pb4Zn8(PO4)8 and alpha-BaZn2(PO4)2 are two-dimensional layered structures with
      [Zn4P4O16]infinity layers for Pb4Zn8(PO4)8 and [Zn3P3O12]infinity honeycomb
      double layers for alpha-BaZn2(PO4)2. And in the structure of Pb4Zn8(PO4)8, there
      are four different Zn-P-O layers, which is reported for the first time in zinc
      phosphates. In addition, thermal property analysis, and UV-Vis-NIR diffuse
      reflectance and infrared spectroscopy were also performed. First-principles
      theoretical studies were also conducted to aid the understanding of their band
      structures and densities of states.

PMID- 29022970
TI  - MSAll strategy for comprehensive quantitative analysis of PEGylated-doxorubicin,
      PEG and doxorubicin by LC-high resolution q-q-TOF mass spectrometry coupled with
      all window acquisition of all fragment ion spectra.
AB  - The covalent attachment of polyethylene glycol (PEG) to therapeutic compounds
      (known as PEGylation) is one of the most promising techniques to improve the
      biological efficacy of small molecular weight drugs. After administration,
      PEGylated prodrugs can be metabolized into pharmacologically active compounds so
      that PEGylated drug, free drug and released PEG are present simultaneously in the
      body. Understanding the pharmacokinetic behavior of these three compounds is
      needed to guide the development of pegylated theranostic agents. However, PEGs
      are polydisperse molecules with a wide range of molecular weights, so that the
      simultaneous quantitation of PEGs and PEGylated molecules in biological matrices
      is very challenging. This article reports the application of a data-independent
      acquisition method (MSAll) based on liquid chromatography electrospray ionization
      quadrupole time-of-flight mass spectrometry (LC-q-q-TOF-MS) in the positive ion
      mode to the simultaneous determination of methoxyPEG2000-doxorubicin (mPEG2K-Dox)
      and its breakdown products in rat blood. Using the MSAll technique, precursor
      ions of all molecules are generated in q1, fragmented to product ions in q2
      (collision cell), and subjected to TOF separation before precursor and product
      ions are recorded using low and high collision energies (CE) respectively in
      different experiments for a single sample injection. In this study, dissociation
      in q2 generated a series of high resolution PEG-related product ions at m/z
      89.0611, 133.0869, 177.1102, 221.1366, 265.1622, 309.1878, and 353.2108
      corresponding to fragments containing various numbers of ethylene oxide subunits,
      Dox-related product ions at m/z 321.0838 and 361.0785, and an mPEG2K-Dox specific
      product ion at m/z 365.0735. Detection of mPEGs and mPEG2K-Dox was based on high
      resolution extracted ions of mPEG and the specific compound. The method was
      successfully applied to a pharmacokinetic study of doxorubicin, mPEG2K
      (methylated polyethylene glycol 2K), and mPEG2K-doxorubicin in rats after a
      single intravenous injection of mPEG2K-doxorubicin. To the best of our knowledge,
      this is the first assay that simultaneously determines mPEG, Dox, and mPEG2K-Dox
      in a biological matrix. We believe the MSAll technique as applied in this study
      can be potentially extended to the determination of other PEGylated small
      molecules or polymeric compounds.

PMID- 29022971
TI  - Elastic moduli of biological fibers in a coarse-grained model: crystalline
      cellulose and beta-amyloids.
AB  - We study the mechanical response of cellulose and beta-amyloid microfibrils to
      three types of deformation: tensile, indentational, and shear. The cellulose
      microfibrils correspond to the allomorphs Ialpha or Ibeta whereas the beta
      amyloid microfibrils correspond to the polymorphs of either two- or three-fold
      symmetry. This response can be characterized by three elastic moduli, namely, YL,
      YT, and S. We use a structure-based coarse-grained model to analyze the
      deformations in a unified manner. We find that each of the moduli is almost the
      same for the two allomorphs of cellulose but YL is about 20 times larger than YT
      (140 GPa vs. 7 GPa), indicating the existence of significant anisotropy. For
      cellulose we note that the anisotropy results from the involvement of covalent
      bonds in stretching. For beta-amyloid, the sense of anisotropy is opposite to
      that of cellulose. In the three-fold symmetry case, YL is about half of YT (3 vs.
      7) whereas for two-fold symmetry the anisotropy is much larger (1.6 vs. 21 GPa).
      The S modulus is derived to be 1.2 GPa for three-fold symmetry and one half of it
      for the other symmetry and 3.0 GPa for cellulose. The values of the moduli
      reflect deformations in the hydrogen-bond network. Unlike in our theoretical
      approach, no experiment can measure all three elastic moduli with the same
      apparatus. However, our theoretical results are consistent with various measured
      values: typical YL for cellulose Ibeta ranges from 133 to 155 GPa, YT from 2 to
      25 GPa, and S from 1.8 to 3.8 GPa. For beta-amyloid, the experimental values of S
      and YT are about 0.3 GPa and 3.3 GPa respectively, while the value of YL has not
      been reported.

PMID- 29022972
TI  - Heterogeneous mesoporous manganese/cobalt oxide catalysts for selective oxidation
      of 5-hydroxymethylfurfural to 2,5-diformylfuran.
AB  - We report a heterogeneous catalytic protocol for the oxidation of 5
      hydroxymethylfurfural (HMF) to 2,5-diformylfuran (DFF) using a mesoporous
      manganese doped cobalt oxide material. The absence of precious metals and
      additives, use of air as the sole oxidant, and easy isolation of products, along
      with proper catalyst reusability, make our catalytic protocol attractive for the
      selective oxidation of HMF to DFF.

PMID- 29022974
TI  - The mechanism of cesium ions immobilization in the nanometer channel of calcium
      silicate hydrate: a molecular dynamics study.
AB  - The cement-based matrices are preferred candidates in disposing nuclear waste due
      to the immobilization role of the calcium-silicate-hydrate (C-S-H) gel. To better
      understand the immobilization mechanism of cementitious materials, molecular
      dynamics was utilized to investigate the intensity distribution, local structure
      and dynamics properties of Cs+ ions in the vicinity of the calcium silicate
      surface. The strong inner-sphere adsorbed cesium ions were restricted by
      coordinated oxygen atoms in bridging and pair silicate tetrahedron and water
      molecules were fixed in the silicate channel by H-bonds network. On the other
      hand, the adsorption of chloride ion, repulsed by the negatively charged silicate
      surface, is mainly attributed to the formation of the cation-anion ionic pair
      near the interface. As compared with those of the solvated ions in the solution,
      the relaxation time of water in the hydration shell of adsorbed Cs+ is
      significantly increased and the diffusion coefficient of adsorbed Cs+ is
      dramatically reduced. Furthermore, based on the intensity profile and resident
      time analysis, the adsorption capacities of monovalent cations on the C-S-H
      surface increase with decrease in the ionic radius, following the sequence of Na+
      ? K+ > Cs+. This study provides a molecular-level understanding of the
      immobilization mechanism of different ions in the C-S-H gel pores.

PMID- 29022977
TI  - Effect of lithium-trapping on nitrogen-doped graphene as an anchoring material
      for lithium-sulfur batteries: a density functional theory study.
AB  - N-Doped graphene (NG) has been widely used as a cathode material for lithium
      sulfur (Li-S) batteries due to its strong interaction with lithium polysulfide
      (LiPS) species. However, strong interaction between the NG substrate and the LiPS
      molecules induces undesirable molecular structure decomposition of LiPS. Due to
      the strong interaction between Li and NG, Li-trapping occurs during battery
      operation. Therefore, in this study, Li-trapped NG (LiNG) is introduced as a
      possible structure of NG, and the structural stability of LiNG under applied
      electric potential is examined. The effect of Li-trapping on the properties of NG
      as an anchoring material for Li-S batteries is investigated using density
      functional theory calculations. Li-trapping relieves the strong interaction
      between NG and LiPS, thereby avoiding decomposition of the LiPS molecule.
      Although the interaction between the LiPS molecule and the substrate is weakened,
      additionally formed interaction after Li-trapping, which is between Li in the
      substrate and S in the molecule, enables LiNG to suppress the shuttle effect.
      LiNG shows advanced anchoring behavior that suppresses the shuttle effect without
      any molecular decomposition of LiPS. This finding provides a further
      understanding of the effect of Li-trapping on the anchoring properties of NG for
      Li-S batteries.

PMID- 29022979
TI  - The antibacterial and antibiofilm efficacies of a liposomal peptide originating
      from rice bran protein against Listeria monocytogenes.
AB  - With the aim of exploring a natural antilisterial peptide from food-derived
      origin, an antibacterial peptide named as Alpep7 was purified from the bromelain
      hydrolysate of rice bran protein (RBP) in this study. The resulting amino acid
      consequence was identified as KVDHFPL (Lys-Val-Asp-His-Phe-Pro-Leu) by
      ultraperformance liquid chromatography tandem matrix-assisted laser
      desorption/ionisation quadrupole time-of-flight mass spectrometry (MALDI Q-TOF
      MS). In addition, to assess the probability of the targeted delivery of liposome
      encapsulation of the peptide to Listeria biofilm, Alpep7-loaded liposomes were
      further prepared from a mixture of dipalmitoylphosphatidylcholine, stearylamine
      and cholesterol in a molar ratio of 10 : 3 : 2 and characterised by the analysis
      of particle size, zeta potential, microtopography and storage stability. The
      results showed that the liposomes exhibited a well-defined spherical shape, with
      an average diameter below 200 nm. The liposomes maintained favourable stability
      after storage at 4  degrees C for 4 weeks. Comparisons between the activities of
      free and liposomal Alpep7 via microbroth dilution, regrowth analysis and confocal
      scanning laser microscopy suggested that liposomal delivery was more effective
      during the initial exposure of the liposomes to the biofilms. The thermodynamic
      analysis indicated that the adsorption of liposomal Alpep7 to the listerial
      biofilm was a spontaneous, exothermic process. The results may provide a natural
      means for the treatment of listerial contamination and guide the potential
      application of liposomes for the targeted delivery of antimicrobials to
      pathogenic biofilms in the food industry.

PMID- 29022980
TI  - The effect of compressed CO2 on the self-assembly of surfactants for facile
      preparation of ordered mesoporous carbon materials.
AB  - The effect of compressed CO2 on the properties of ordered mesoporous carbon (OMC)
      was investigated based on the self-assembly of surfactants in aqueous solution
      under mild conditions, and the acidic or basic conditions commonly used in
      traditional methods were substituted by compressed CO2. Compressed CO2 acts as
      both a physiochemical additive and a reagent to produce an acid catalyst in the
      synthesis. This new one-pot assembly approach can efficiently adjust the porous
      characteristics of OMC by employing different amounts of compressed CO2, and the
      self-assembly mechanism is proposed. The spherical micelles formed by triblock
      copolymer Pluronic F127 serve as a structure-directing agent for the controllable
      synthesis of nanomaterials. Resorcinol/phloroglucinol and formaldehyde are used
      as carbon-yielding components. It was found that CO2 can penetrate into the
      hydrocarbon-chain region of the F127 micelles, leading to template swelling and
      influencing the properties of OMC. The surfactant and precursors attracted by H
      bonding interactions self-assemble and produce OMC after polymerization and
      carbonization. The resulting OMC as a supercapacitor electrode material exhibits
      outstanding specific capacitances, and the electrochemical performances change as
      the structural properties are varied.

PMID- 29022978
TI  - Freeze-dried strawberry and blueberry attenuates diet-induced obesity and insulin
      resistance in rats by inhibiting adipogenesis and lipogenesis.
AB  - Obesity and type 2-diabetes are becoming a worldwide health problem, reiterating
      the importance of alternative therapies to tackle their progression. Here, we
      hypothesized that supplementation of diet with 6% w/w of a freeze-dried
      strawberry-blueberry (5 : 1) powder (FDSB) could exert beneficial metabolic
      effects on Wistar rats. FDSB-supplemented animals experienced significantly
      reduced body weight gain, food efficiency and visceral adiposity accumulation in
      two independent experiments. FDSB supplementation also contributed to lower area
      under the curve after an intraperitoneal GTT and reduced serum insulin levels and
      an insulin resistance index (IR-HOMA) in HFS diet-fed animals, together with
      reduced plasma MCP-1 inflammation marker concentrations. Gene expression analysis
      in retroperitoneal adipocytes from experiment 1 and 3T3-L1 cells showed that FDSB
      inhibited adipogenesis and lipogenesis through down-regulation of Pparg, Cebpa,
      Lep, Fasn, Scd-1 and Lpl gene expression. Untargeted metabolomics identified the
      cis isomer of resveratrol-3-glucoside-sulphate as a metabolite differentially
      increased in FDSB-treated serum samples, which corresponds to a strawberry
      metabolite that could be considered a serum biomarker of FDSB-intake. Our results
      suggest that FDSB powder might be useful for treatment/prevention of obesity
      related diseases.

PMID- 29022982
TI  - Repelling and ordering: the influence of poly(ethylene glycol) on protein
      adsorption.
AB  - Development of new materials for drug delivery and biosensing requires the fine
      tuning of interfacial properties. We report here the influence of the
      poly(ethylene glycol) (PEG) grafting density in model phospholipid monolayers on
      the adsorption behavior of bovine serum albumin and human fibrinogen, not only
      with respect to the amount of adsorbed protein, but also its orientational
      ordering on the surface. As expected, with increasing interfacial PEG density,
      the amount of adsorbed protein decreases up to the point where complete protein
      repellency is reached. However, at intermediate concentrations, the net
      orientation of adsorbed fibrinogen is highest. The different proteins respond
      differently to PEG, not only in the amount of protein adsorbed, but also in the
      manner that proteins adsorb. The results show that for specific cases, tuning the
      interfacial PEG concentration allows to guide the protein adsorption
      configuration, a feature sought after in materials for both biosensing and
      biomedical applications.

PMID- 29022985
TI  - Correction: A bioenergetic mechanism for amoeboid-like cell motility profiles
      tested in a microfluidic electrotaxis assay.
AB  - Correction for 'A bioenergetic mechanism for amoeboid-like cell motility profiles
      tested in a microfluidic electrotaxis assay' by Hagit Peretz-Soroka et al.,
      Integr. Biol., 2017, DOI: .

PMID- 29022983
TI  - A tuneable microfluidic system for long duration chemotaxis experiments in a 3D
      collagen matrix.
AB  - In many cell types, migration can be oriented towards a chemical stimulus. In
      mammals, for example, embryonic cells migrate to follow developmental cues,
      immune cells migrate toward sites of inflammation, and cancer cells migrate away
      from the primary tumour and toward blood vessels during metastasis. Understanding
      how cells migrate in 3D environments in response to chemical cues is thus crucial
      to understanding directed migration in normal and disease states. To date,
      chemotaxis in mammalian cells has been primarily studied using 2D migration
      models. However, it is becoming increasingly clear that the mechanisms by which
      cells migrate in 2D and 3D environments dramatically differ, and cells in their
      native environments are confronted with a complex chemical milieu. To address
      these issues, we developed a microfluidic device to monitor the behaviour of
      cells embedded in a 3D collagen matrix in the presence of complex concentration
      fields of chemoattractants. This tuneable microsystem enables the generation of
      (1) homogeneous, stationary gradients set by a purely diffusive mechanism, or (2)
      spatially evolving, stationary gradients, set by a convection-diffusion
      mechanism. The device allows for stable gradients over several days and is large
      enough to study the behaviour of large cell aggregates. We observe that primary
      mature dendritic cells respond uniformly to homogeneous diffusion gradients,
      while cell behaviour is highly position-dependent in spatially variable
      convection-diffusion gradients. In addition, we demonstrate a directed response
      of cancer cells migrating away from tumour-like aggregates in the presence of
      soluble chemokine gradients. Together, this microfluidic device is a powerful
      system to observe the response of different cells and aggregates to tuneable
      chemical gradients.

PMID- 29022987
TI  - Double-mesoporous core-shell nanosystems based on platinum nanoparticles
      functionalized with lanthanide complexes for in vivo magnetic resonance imaging
      and photothermal therapy.
AB  - A double-mesoporous nanosystem was synthesized for treating as well as imaging
      cancer cells by using a simple and mild method. The mesoporous platinum (Pt)
      nanoparticles acting as a core show excellent photothermal effect under
      illumination with an 808 nm near infrared (NIR) laser. The mesoporous silica
      linked with a lanthanide (Gd) complex acting as a shell displays potential
      applications as a contrast agent for magnetic resonance imaging (MRI). The final
      mPt@mSiO2-GdDTPA nanosystems exhibit good biocompatibility in vitro and in vivo,
      when investigated by methyl thiazolyl tetrazolium assay and histological and
      serum biochemistry analysis. The investigation of the photothermal effect shows
      that the mPt@mSiO2-GdDTPA nanosystems exhibit an excellent photothermal therapy
      effect on HeLa cells and tumor-bearing mice. As theranostic agents, the
      nanosystems display a higher r1 value than the medical contrast agent magnevist
      and were successfully applied to in vivo MRI of Kunming mice. Therefore, the
      first systematic study on the photothermal effect of nanosystems based on
      mesoporous Pt nanoparticles does encourage the potential applications of metal
      nanoparticles and hybrid nanocomposites for cancer bioimaging and therapy.

PMID- 29022988
TI  - A microporous MOF with open metal sites and Lewis basic sites for selective CO2
      capture.
AB  - A robust indium-organic framework (InOF-15) with open metal sites and Lewis basic
      sites has been successfully synthesized using a quinoline-based dicarboxylic
      acid. Moreover, it exhibits high IAST selective CO2 sorption from CO2/CH4 and
      CO2/N2 mixtures at 273 K, which has been attributed to the coexistence of OMSs
      and LBSs with strong synergistic effects.

PMID- 29022989
TI  - Prophylactic intravenous calcium therapy for exchange blood transfusion in the
      newborn.
AB  - BACKGROUND: Exchange blood transfusion (EBT) is a form of whole blood transfusion
      in which the total blood volume is replaced within a few hours. In perinatal and
      neonatal medicine, EBT is most often used in the management of severe anaemia or
      severe hyperbilirubinaemia in the first week of life. Hypocalcaemia, one of the
      common morbidities associated with EBT, is thought to arise from the chelating
      effects of the citrate commonly used as an anticoagulant in the donor's blood.
      This disorder manifests with muscular and nervous irritability and cardiac
      arrhythmias. OBJECTIVES: To determine whether the use of prophylactic calcium
      reduces the risk of hypocalcaemia-related morbidities and death among newborn
      infants receiving EBT. SEARCH METHODS: We used the standard search strategy of
      the Cochrane Neonatal Review group to search the Cochrane Central Register of
      Controlled Trials (CENTRAL 2016, Issue 5), MEDLINE via PubMed (1966 to 29 June
      2016), Embase (1980 to 29 June 2016), and CINAHL (1982 to 29 June 2016). We also
      searched clinical trials databases, conference proceedings, and the reference
      lists of retrieved articles for randomised controlled trials and quasi-randomised
      trials. SELECTION CRITERIA: All randomised and quasi-randomised trials of
      prophylactic intravenous calcium in EBT for newborns. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed and extracted data on
      methods, participants, interventions, and outcomes (mean total and ionised serum
      calcium before and after EBT and the presence of adverse events such as
      hypoglycaemia, apnoea, cardiac arrest, and death immediately after EBT). We
      reported results as means difference (MD) with 95% confidence intervals (CI) for
      continuous outcomes and risk ratio (RR) and risk differences (RD) and 95% CIs for
      dichotomous outcomes. We assessed quality using the Cochrane 'Risk of bias'
      assessment tool and the GRADE system. MAIN RESULTS: We found only one quasi
      randomised trial with 30 participants that met our inclusion criteria. In the
      small trial, total and ionised serum calcium levels were measured immediately
      before and immediately after EBT. All the participants were included in the final
      analysis and all the important outcomes were reported. Primary outcomesThere was
      one death in each group (RR 1.00, 95% CI 0.07 to 14.55; RD 0.00, 95% CI -0.18 to
      0.18; participants = 30; studies = 1). The study did not report the presence of
      cardiac arrhythmias within one week of EBT and the number of infants with serum
      calcium levels (total less than 8 mg/dL (2 mmol/L) or ionised less than 4.4 mg/dL
      (1.1 mmol/L)).Pair-wise comparison of EBT with intravenous 10% calcium gluconate
      versus EBT without intravenous calcium (change from baseline) showed mean total
      serum calcium was raised in the intervention group compared to the control group
      (MD -0.46, 95% CI -0.81 to -0.11; participants = 30; studies = 1). Very low
      quality evidence also indicated an increase in the levels of mean ionised serum
      calcium in the intervention group compared to the control group (MD -0.22, 95% CI
      -0.33 to -0.11; participants = 30; studies = 1). Secondary outcomesAdverse
      reactions to intravenous calcium therapy included cardiac arrest in one neonate
      in the intervention arm (RR 3.00, 95% CI 0.13 to 68.26; RD 0.07, 95% CI -0.10 to
      0.23; participants = 30; studies = 1). There was apnoea and hypoglycaemia (RR
      1.00, 95% CI 0.07 to 14.55; RD 0.00, 95% CI -0.18 to 0.18; participants = 30;
      studies = 1) in the two neonates who died. Data were not available for other
      major secondary outcomes such as the number of infants with reduced serum
      magnesium, reduced parathormone, increased calcitonin, presence of seizures,
      carpopedal spasm, jitteriness and prolonged QTc interval on electrocardiography
      within one week of EBT. AUTHORS' CONCLUSIONS: Very low-quality data from one
      quasi-randomised controlled trial suggested that the mean serum total and ionised
      calcium increased in the study group but decreased in the control group
      immediately after EBT. However, the mean values of total and ionised calcium in
      both arms of studies remained within international reference ranges.
      Unfortunately, data were not available to assess the trend of total and ionised
      serum calcium to the end of the first week after EBT. Therefore, due to the very
      low quality of evidence available, it is difficult to support or reject the
      continual use of prophylactic intravenous calcium in newborn infants receiving
      EBT. Researchers are encouraged to conduct more robustly designed trials with
      larger numbers of participants, and particularly, addressing the pattern of
      differences based on gestational age of participants, type of anticoagulant used,
      and the volume of blood used.

PMID- 29022990
TI  - Postpartum Fecal and Flatal Incontinence: Silence, Stigma, and Psychological
      Interventions.

PMID- 29022991
TI  - Characterization of Cladosporium Species by Internal Transcribed Spacer-PCR and
      Microsatellites-PCR.
AB  - BACKGROUND: This investigation compared genetic similarities and diversities
      within and among Cladosporium species populations using the two PCR-based
      markers; Internal Transcribed Spacer (ITS)-PCR and microsatellite-PCR.
      METHODOLOGY: Nuclear ribosomal DNA internal transcribed spacers have been used to
      analyze intraspecific and interspecific relationships in various fungi. In the
      present study, the internal transcribed spacer (ITS)-PCR and microsatellite-PCR
      were used to identify the genetic diversities in Cladosporium species. RESULTS:
      The Internal Transcribed Spacer (ITS) was amplified using polymerase chain
      reaction combining primers ITS4 and ITS5. The PCR products were digested with
      three restriction enzymes and separated by agarose gel electrophoresis.
      Restriction patterns generated by CfoI and Msp I and RsaI were unique for most
      species assayed. The ITS-PCR fingerprinting methods led to a clear
      differentiation of the isolates at the species level. Fingerprinting profiles
      generated readily discriminated between each of the 6 species. Cluster analysis
      further supported this observation and clusters corresponding to each species
      were readily identified in the dendrograms. Seven microsatellite primers out of
      eight primers were unable to generate visible DNA fingerprints. CONCLUSION:
      Amplification experiments demonstrated that microsatellite primer, T3B and (GTG)
      5 are technically simple tools for assaying genetic variability in Cladosporium
      spp.

PMID- 29022992
TI  - Growth and Nutrient Status of Kayu Kuku [ Pericopsis mooniana (Thw.) Thw] with
      Mycorrhiza in Soil Media of Nickel Post Mining Site.
AB  - BACKGROUND: Arbuscular Mycorrhizal Fungi are categorized as phytoremediant and
      increase the tolerance of plants under condition of heavy metal pollution.
      Effectiveness of AMF is determined very much by species of AMF, plant species and
      environmental condition. Therefore, testing the effect of local AMF on growth and
      absorption of nutrients and metal by Pericopsis mooniana planting stocks in
      growing media which are heavily polluted by heavy metal, need to be conducted.
      METHODOLOGY: There were testing of 6 inoculums of local AMF which were isolated
      from rhizosphere of P. mooniana, namely AMF from district of Kolaka (Lamedai
      Nature Reserve, Tanggetada Natural Forest, Bali Jaya Village Plantation Forest
      and PT. Vale Indonesia Tbk) and from Kendari town (Campus environment of Halu
      Oleo University and Office of Southeast Sulawesi Governor). Besides the 6 local
      AMF, there were treatment without AMF (control) and treatment with mycofer as
      comparison. RESULTS: Results showed that local AMF were effective in increasing
      growth and biomass of plants; absorption of C, N, P and K in three parts of the
      plants; Ca in stems and leaves and of Mg in leaf tissues; increasing formation of
      plant's root nodules and were able to reduce Ni content in tissues of kayu kuku
      planting stocks. Effects of local AMF from Lamedai nature reserve and AMF from
      PT. Vale Indonesia were greater as compared with those of mycofer IPB. Content of
      Ni in kayu kuku plant tissue was found more in roots as shown by the value of
      TF<1. CONCLUSION: Based on this study, kayu kuku is categorized as excluder
      species (TF<1) and moderate species toward Ni (>50 mg Ni/kg of plant dry weight)
      and possessed very high dependence on AMF (MIE >75%). Local AMF are potential to
      be developed as biological fertilizer to improve planting stocks for
      rehabilitation of degraded land.

PMID- 29022993
TI  - Evaluation of the Antiplasmodial Activity and Lethality of the Leaf Extract of
      Cassia alata L. (Fabaceae).
AB  - OBJECTIVE: Cassia alata L. (Fabaceae), one of the three plants contained in Saye,
      a polyherbal antimalarial remedy was assessed for its antimalarial potential and
      safety in mice. METHODOLOGY: Organic extracts were prepared from the leaves and
      tested on the D 10 chloroquine-sensitive strain of Plasmodium falciparum using
      the parasite lactate dehydrogenase assay. The 4 days suppressive test using
      Plasmodium berghei in mice was used to evaluate the in vivo antiplasmodial
      activity of the extracts. Animals were treated by oral route, once a day with 50,
      100, 250 and 400 mg kg -1 b.wt., of the extracts. The acute toxicity of the
      extracts was assessed in mice according to Thompson and Weil method. The lethal
      effects of the extracts on animal's body weight, tissues, biochemical and
      haematological parameters were determined at 823.5, 1235.5, 1853 and 2779.5 mg kg
      -1 b.wt., respectively. RESULTS: The dichloromethane/methane (1:1, v/v) extract
      of Cassia alata was the most active against Plasmodium falciparum. The mean
      percent suppression of parasitemia in mice was equal to 22.5, 41.8 and 45.2% at
      50, 250 and 400 mg kg -1 b.wt., respectively. No death and no clinically
      significant changes were recorded in mice. The maximum non-lethal dose was more
      than 16875 mg kg -1 in animals. No significant changes were observed in body
      weight, tissues morphology, biochemical and hematological parameters at doses
      above or equal to 2779.5 mg kg -1 b.wt. CONCLUSION: The dichloromethane/methanol
      leaf extract of Cassia alata had a good to moderate in vitro and in vivo
      antiplasmodial activity and was found to have low toxicity at high doses in
      tested animals.

PMID- 29022994
TI  - Evaluation of Hematological and Biochemical Activity of Ethanolic Extract of
      Zygophyllum simplex Linn. in Wistar Rats.
AB  - BACKGROUND AND OBJECTIVE: Zygophyllum simplex is commonly used in Saudi Arabia
      for the treatment of horny patches of skin and as an anthelmintic, analgesic and
      anti-inflammatory. The experiment was to aimed at to evaluate the constituents of
      Zygophyllum simplex extract and their effect on blood biochemical parameters in
      Wistar male rats. METHODOLOGY: The plant extract was orally administered to the
      rats (n = 10) at two doses of 250 and 500 mg kg -1 b.wt., for 30 days. Its
      effects on glucose, total cholesterol, triglycerides, aspartate aminotransferase
      (AST), alanine aminotransferase (ALT), serum creatinine kinase (CK), total
      protein, total bilirubin and blood urea were investigated. RESULTS: The results
      showed a significant decrease in total serum cholesterol, blood glucose and CK
      levels. However, levels of AST, ALT, triglycerides, total bilirubin, total
      protein and blood urea were unaltered. CONCLUSION: In coclusion, the ethanolic
      extract of Z. simplex may act as hypoglycemic and hypolipidimic in rats.

PMID- 29022995
TI  - Measurement of Interleukin-6 in Cerebrospinal Fluid for the Diagnosis of
      Bacterial Meningitis.
AB  - OBJECTIVE: It is assessed whether the measurement of interleukin-6 in the
      cerebrospinal fluid can serve as a biomarker for the diagnosis of bacterial
      meningitis. METHODOLOGY: Cerebrospinal fluid was obtained from 152 patients aged
      0-15 years suspected of having meningitis. These patients were classified into
      the following groups: Bacterial meningitis (n = 85), aseptic meningitis (n = 35)
      and non-meningitis/control (n = 32) based on leukocyte count and bacterial
      identification by culture and molecular biology. Interleukin-6 concentrations in
      cerebrospinal fluid were measured by enzyme-linked immunosorbent assay. RESULTS:
      This study found a significant difference of the mean cerebrospinal fluid
      interleukin-6 level (p<=0.01) between patients with bacterial meningitis
      (3,538.69+/-2,560.78 pg mL -1) and patients with aseptic meningitis (332.51+/
      470.69 pg mL -1) or those of the control group (205.83+/-79.39 pg mL -1). There
      was also a significant difference of the mean cerebrospinal fluid interleukin-6
      level between patients with aseptic meningitis and those of the control group.
      Interleukin-6 had the highest area under the ROC curve: 0.94 (95% confidence
      interval: 0.901-0.979) compared to that of cerebrospinal fluid glucose and total
      protein. At a cut-off value of 1,065.96 pg mL -1, interleukin-6 had a sensitivity
      of 76.2% and specificity of 100%. CONCLUSION: Interleukin-6 is a potential
      biomarker for the differential diagnosis of meningitis.

PMID- 29022996
TI  - Molecular Epidemiology of Rotavirus in Children under Five in Africa (2006-2016):
      A Systematic Review.
AB  - Group A human rotaviruses (RVA) are the most common causes of severe viral
      gastroenteritis in infants and young children worldwide. The available vaccines,
      while effective in Europe and North America have shown a reduced efficacy in
      Africa. One issue raised is the genetic variability of RVA. The objective of this
      study was to perform a literature review of molecular epidemiology to determine
      the prevalence of RVA genotypes circulating in Africa so as to establish a
      mapping of reliable data on these various genotypes. The search for articles was
      done from the National Institutes of Health (PUBMED) using three set of keywords.
      Articles were selected with inclusion criteria such as the date of publication,
      the age of the children, the sample size and the diagnostic techniques
      (standardized laboratory techniques). The data were imported into STATA SE
      version 11 software. Specific prevalence was estimated with Confidence Intervals
      (CI) of 95%. A total of 326 published studies were initially retrieved, out of
      which 27 studies were finally selected for the systematic review. The selected
      studies cover 20 African countries. The most encountered genotypes in Africa
      during this period were G1 (32.72%), followed by G2 (17.17%), G3 (9.88%), G9
      (8.61%) and G12 (7.56%) among the G-types. The most common P-types were P[8]
      (48.71%) followed by P[6] (22.60%) and P[4] (11.58%) and the G1P[8] combination
      (22.64%) was the most encountered followed by G2P[4] (8.29%), G9P[8] (6.95%) and
      G2P[6] (5.00%). North Africa presented the highest prevalence of the P[8]
      genotype (65.70%). This review provides a comprehensive view of the current
      circulating rotavirus strains in Africa, which can be important in light of the
      new rotavirus vaccinations. Indeed, in Africa, the pursuit of national and
      continental studies for epidemiological surveillance of circulating rotavirus
      strains is vital for the promotion of future successful vaccines.

PMID- 29022997
TI  - Phytochemical Analysis, Identification and Quantification of Antibacterial Active
      Compounds in Betel Leaves, Piper betle Methanolic Extract.
AB  - BACKGROUND AND OBJECTIVE: The problems of bacterial diseases in aquaculture are
      primarily controlled by antibiotics. Medicinal plants and herbs which are seemed
      to be candidates of replacements for conventional antibiotics have therefore
      gained increasing interest. Current study was performed to investigate the
      presence of phytochemical constituents, antibacterial activities and composition
      of antibacterial active compounds in methanolic extract of local herb, Piper
      betle . METHODOLOGY: Qualitative phytochemical analysis was firstly carried out
      to determine the possible active compounds in P. betle leaves methanolic extract.
      The antibacterial activities of major compounds from this extract against nine
      fish pathogenic bacteria were then assessed using TLC-bioautography agar overlay
      assay and their quantity were determined simultaneously by HPLC method. RESULTS:
      The use of methanol has proved to be successful in extracting numerous bioactive
      compounds including antibacterial compounds. The TLC-bioautography assay revealed
      the inhibitory action of two compounds which were identified as hydroxychavicol
      and eugenol. The $-caryophyllene however was totally inactive against all the
      tested bacterial species. In this study, the concentration of hydroxychavicol in
      extract was found to be 374.72+/-2.79 mg g-1, while eugenol was 49.67+/-0.16 mg g
      1. CONCLUSION: Based on these findings, it could be concluded that
      hydroxychavicol and eugenol were the responsible compounds for the promising
      antibacterial activity of P. betle leaves methanolic extract. This inhibitory
      action has significantly correlated with the amount of the compounds in extract.
      Due to its potential, the extract of P. betle leaves or it compounds can be
      alternative source of potent natural antibacterial agents for aquaculture disease
      management.

PMID- 29022998
TI  - Synthesis, Characterization and Antimicrobial Activities of Copper Derivatives of
      NHC-II Complexes.
AB  - BACKGROUND: Caffeine, 1, 3, 7-trimethylxanthine is one of the xanthine
      derivatives that are for the most part utilized as a part of solutions as
      diuretics. The Cu (II) complexes have been synthesized from the N-heterocyclic
      carbene ligands. MATERIALS AND METHODS: The Cu (II) NHC complexes were
      characterized using analytical and spectral techniques. Antibacterial and
      antifungal activities of the Cu (II) NHC complexes were determined using the
      reported techniques. The SOD activity was assayed using nitrobluetetrazolium as
      O2 scavenger. RESULTS: The X-band ESR spectra of the copper complexes in DMSO
      solution at 300 and 77 K were recorded and their salient features are reported.
      The in vitro biological screening effects of the investigated compounds were
      tested against the bacterial species, Staphylococcus aureus, Escherichia coli,
      Klebsiella pneumoniae, Proteus vulgaris and Pseudomonas aeruginosa and fungal
      species, Aspergillus niger, Rhizopus stolonifer, Aspergillus flavus, Rhizoctonia
      bataicola and Candida albicans by serial dilution method. CONCLUSION: The Cu (II)
      complexes exhibit square planar geometry. A comparative study of inhibition
      values of the individual metals and their complexes indicate that the complexes
      exhibit higher antimicrobial activity than the individual metals. Superoxide
      dismutase and reducing power activities of the copper complexes have also been
      studied. Depending on the molecular structure, the Cu (II) NHC complex possess
      promising SOD mimetic activities. Further we are trying to explore more
      biological properties of Cu (II) NHC complexes in vitro and in vivo.

PMID- 29022999
TI  - Effects of Selenium Application on Plant Growth and Some Quality Parameters in
      Peanut (Arachis hypogaea).
AB  - BACKGROUND AND OBJECTIVE: Selenium (Se) is an essential plant micronutrient and
      has been repetedly shown to enhance crop growth and crop tolerance to abiotic
      stresses when applied in trace amounts. However, physiological responses of
      different plants vary significantly to the Se fertilizer application. The aim of
      this study was to investigate the effect of Se application on yield and quality
      parameters of peanut under field conditions. MATERIALS AND METHODS: A pot
      experiment was conducted where Se fertilizer was applied (i) To soil at 5
      different doses, (ii) As folier fertilizer or (iii) Via seed soaking at 4
      different doses. Two years field experiments were conducted under East
      Mediterranean conditions of Turkey. RESULTS: The yields were significantly
      increased by all types of Se applications. The highest yield (6130 kg ha-1) was
      obtained from foliar applications made 40 days after flowering. Increasing doses
      of Se increased 100 grain weight but oil, protein and nitrogen content of grains
      were not affected. CONCLUSION: Two years experiment clearly showed that external
      Se supply to peanut (all methods tested) increased yield formation in East
      Mediterranean conditions of Turkey. Here, particularly foliar application (3%
      sodium selenite) of Se 40 after flowering seems to be most effective way for its
      application.

PMID- 29023000
TI  - Application of Response Surface Methodology for Optimization of Extracellular
      Glucoamylase Production by Candida guilliermondii.
AB  - OBJECTIVE: Glucoamylase is among the most important enzymes in biotechnology. The
      present study aims to determine better conditions for growth and glucoamylase
      production by Candida guilliermondii and to reduce the overall cost of the medium
      using Box-Behnken design with one central point and response surface methodology.
      METHODOLOGY: Box-Behnken factorial design based on three levels was carried out
      to obtain optimal medium combination of five independent variables such as
      initial pH, soluble starch, CH4N2O, yeast extract and MgSO4. Forty one randomized
      mediums were incubated in flask on a rotary shaker at 105 rpm for 72 h at 30
      degrees C. RESULTS: The production of biomass was found to be pH and starch
      dependent, maximum production when the starch concentration was 8 g L-1 and the
      initial pH was 6, while maximum glucoamylase production was found at 6.5 of
      initial pH, 4 g L-1 yeast extract and 6 g L-1 starch, whereas yeast extract and
      urea were highly significant, but interacted negatively. Box-Behnken factorial
      design used for the analysis of treatment combinations gave a second-order
      polynomial regression model with R2 = 0.976 for Biomass and R2 = 0.981 for
      glucoamylase. CONCLUSION: The final biomass and glucoamylase activity obtained
      was very close to the calculated parameters according to the p-values (p<0.001),
      the predicted optimal parameters were confirmed and provides a basis for further
      studies in baking additives and in the valuation of starch waste products.

PMID- 29023001
TI  - Evaluation of a New and Rapid Serologic Test for Detecting Brucellosis: Brucella
      Coombs Gel Test.
AB  - BACKGROUND: Many serological tests have been used for the diagnosis of human
      brucellosis. A new serological method is identified as Brucella Coombs gel test
      based on the principle of centrifugation gel system similar to the gel system
      used in blood group determination. In this system, if Brucella antibodies were
      present in the serum, antigen and antibody would remain as a pink complex on the
      gel. Otherwise, the pink Brucella antigens would precipitate at the bottom of the
      gel card system. OBJECTIVE: In this study, we aimed to compare the Brucella
      Coombs gel test, a new, rapid screen and titration method for detection of non
      agglutinating IgG with the Brucella Coombs test. MATERIALS AND METHODS: For this
      study, a total of 88 serum samples were obtained from 45 healthy persons and 43
      individuals who had clinical signs and symptoms of brucellosis. For each
      specimen, Rose Bengal test, standard agglutination test, Coombs test and Brucella
      Coombs gel test were carried out. RESULTS: Sensitivity and specificity of
      Brucella Coombs gel test were found as 100.0 and 82.2%, respectively. CONCLUSION:
      Brucella Coombs gel test can be used as a screening test with high sensitivity.
      By the help of pink Brucella antigen precipitation, the tests' evaluation is
      simple and objective. In addition, determination of Brucella antibody by rapid
      titration offers another important advantage.

PMID- 29023002
TI  - Dynamics of Huanglongbing-associated Bacterium Candidatus Liberibacter asiaticus
      in Citrus aurantifolia Swingle (Mexican Lime).
AB  - BACKGROUND: The bacterial disease citrus huanglongbing (HLB), associated with
      "Candidatus Liberibacter asiaticus" (C.Las) has severely impacted the citrus
      industry, causing a significant reduction in production and fruit quality. In the
      present study, it was monitored the C.Las population dynamics in symptomatic, HLB
      positive Mexican lime trees (Citrus aurantifolia Swingle) in a tropical, citrus
      producing area of Mexico. The objective of this study was to identify the
      dynamics of the population of huanglongbing-associated bacterium Candidatus
      Liberibacter asiaticus and its insect vector in Citrus aurantifolia Swingle
      (Mexican lime). MATERIALS AND METHODS: Leaf samples were collected every 2 months
      over a period of 26 months for quantification of bacterial titers and young and
      mature leaves were collected in each season to determine preferential sites of
      bacterial accumulation. The proportion of living and dead bacterial cells could
      be determined through the use of quantitative real-time PCR in the presence of
      ethidium monoazide (EMA-qPCR). RESULTS: It was observed a lower bacterial titer
      at high temperatures in the infected trees relative to titers in mild weather,
      despite a higher accumulation of the insect vector Diaphorina citri in these
      conditions. This study also revealed seasonal fluctuations in the titers of
      bacteria in mature leaves when compared to young leaves. No statistically
      significant correlation between any meteorological variable, C.Las concentration
      and D. citri population could be drawn. CONCLUSION: Although, HLB management
      strategies have focused on vector control, host tree phenology may be important.
      The evaluation of citrus phenology, C.Las concentration, ACP population and
      environmental conditions provides insights into the cyclical, seasonal variations
      of both the HLB pathogen and its vector. These findings should help in the design
      of integrative HLB control strategies that take into account the accumulation of
      the pathogen and the presence of its vector.

PMID- 29023003
TI  - Antioxidant and Biological Activities of Proteinaceous Extract from Algerian
      Glycine max Plant.
AB  - OBJECTIVE: Glycine max is commonly used in Algeria for treatment of anemia
      deficiency and osteoporosis, it ranks first in terms of vegetal proteins. The
      experiment was aimed at characterizing the proteinaceous Glycine max extract and
      evaluating its antioxidant, biological and hematological potential. METHODOLOGY:
      Extraction of proteinaceous materials from Glycine max plant was undertaken using
      water and n-hexane as extracting media. The isolation of proteins from the crude
      materials was done, providing the use of ammonium sulfate. The Glycine max
      proteins were characterized by UV-visible and FT-IR spectroscopy and analyzed by
      SEM micrograph and x-ray diffraction (XRD). Rheological parameters G' and G''
      were assessed. The isolated proteins were tested for their antioxidant,
      antimicrobial and hemagglutination activities. RESULTS: There was a gelling
      effect of the protein extract which can be used as an alternative in principally
      made vaccines with its microbiological and antifungal activities. CONCLUSION: The
      proteinaceous extract from Algerian Glycine max would have a potential use in
      biomedical application.

PMID- 29023004
TI  - Selection of Drought Tolerant Maize Hybrids Using Path Coefficient Analysis and
      Selection Index.
AB  - BACKGROUND: In drought-prone environments, direct selection for yield is not
      adequate because of the variable environment and genotype x environment
      interaction. Therefore, the use of secondary traits in addition to yield has been
      suggested. The relative usefulness of secondary traits as indirect selection
      criteria for maize grain yield is determined by the magnitudes of their genetic
      variance, heritability and genetic correlation with the grain yield. MATERIALS
      AND METHODS: Forty eight testcross hybrids derived from lines with different
      genetic background and geographical origins plus 7 checks were evaluated in both
      well-watered and water-stressed conditions over two years for grain yield and
      secondary traits to determine the most appropriate secondary traits and select
      drought tolerant hybrids. RESULTS: Study found that broad-sense heritability of
      grain yield and Ear Per Plant (EPP) increased under drought stress. Ear aspect
      (EASP) and ear height (EHT) had larger correlation coefficients and direct effect
      on grain yield but in opposite direction, negative and positive respectively.
      Traits like, EPP, Tassel Size (TS) and Plant Recovery (PR) contributed to
      increase yield via EASP by a large negative indirect effect. Under drought
      stress, EHT had positive and high direct effect and negative indirect effect via
      plant height on grain yield indicating that the ratio between ear and plant
      heights (R-EPH) was associated to grain yield. CONCLUSION: Path coefficient
      analysis showed that traits EPP, TS, PR, EASP, R-EPH were important secondary
      traits in the present experiment. These traits were used in a selection index to
      classify hybrids according to their performance under drought. The selection
      procedure included also a Relative Decrease in Yield (RDY) index. Some secondary
      traits reported as significant selection criteria for selection under drought
      stress were not finally established in the present study. This is because the
      relationship between grain and secondary traits can be affected by various
      factors including germplasm, environment and applied statistical analysis.
      Therefore, different traits and selection procedure should be applied in the
      selection process of drought tolerant genotypes for diverse genetic materials and
      growing conditions.

PMID- 29023005
TI  - Study on Carapace Width Growth Band Counts Relationship of Orange Mud Crab,
      Scylla olivacea (Herbst, 1796) from Terengganu Coastal Waters, Malaysia.
AB  - BACKGROUND: Orange mud crab Scylla olivacea is one of the most important
      fisheries resources. A new development in ageing technique of crustaceans has
      been introduced. The detection of growth band deposited in hard structure of
      gastric mill in the cardiac stomach are found retained after moulting process can
      be used as age indicator and growth estimation. OBJECTIVE: This study was carried
      out to determine the comparison between carapace width and growth band count of
      S. olivacea in Malaysia. MATERIALS AND METHODS: Samples were collected from Setiu
      Wetlands, Terengganu, Malaysia from February until August, 2016. Samples were
      categorized based on their morphological measurements. The mesocardiac and
      zygocardiac ossicles in the gastric mill of S. olivacea was dissected out and
      preserved in solutions and underwent a cross sectioning process. A total of 76 of
      wild S. olivacea ranging from 6.56 to 12.84 cm in carapace width were analysed.
      The growth band counts were examined for each individual and ranging from 1 to 3
      band counts. RESULTS: A positive linear relation was observed between CW and GBC
      with r2 = 0.5178, p<0.01. Overall, there was a strong, positive correlation
      between CW and GBC. Increase in CW were correlated with increases in GBC
      respectively for this species. CONCLUSION: Therefore, the carapace width, growth
      band counts and body weight can be used to improve data on growth, recruitment,
      maturation and mortality. Thus, this study would able to improve new ageing
      technique and contribute greatly to improve the conservation and management of S.
      olivacea in Setiu Wetlands, Terengganu, Malaysia.

PMID- 29023006
TI  - Expression Profile of Stress-responsive Arabidopsis thaliana miRNAs and their
      Target Genes in Response to Inoculation with Pectobacterium carotovorum subsp.
      carotovorum.
AB  - BACKGROUND: Pectobacterium carotovorum subsp. carotovorum (Pcc) is a soft rot
      bacterium which upon entry into the plant macerates plant tissues by producing
      plant cell wall degrading enzymes. It has a wide host range which includes
      carrot, potato, tomato, leafy greens, squash and other cucurbits, onion, green
      peppers and cassava. During plant-microbe interactions, one of the ways of plant
      response to pathogen infection is through the small RNA silencing mechanism.
      Under pathogen attack the plant utilizes microRNAs to regulate gene expression by
      means of mediating gene silencing at transcriptional and post-transcriptional
      level. This study aims to assess for the first time, the expression profile of
      some stress-responsive miRNA and differential expression pattern of their target
      genes in Arabidopsis thaliana inoculated with Pcc. MATERIALS AND METHODS: Leaves
      of five weeks old Arabidopsis thaliana plants were infected with Pcc and the
      quantitative real time-PCR, was used to investigate after 0, 24, 48 and 72 h post
      infection, the expression profiling of the stress-responsive miRNAs which
      include: miR156, miR159, miR169, miR393, miR396 miR398, miR399 and miR408 along
      with their target genes which include: Squamosa promoter-binding-like protein,
      myb domain protein 101, nuclear factor Y subunit A8, concanavalin A-like lectin
      protein kinase, growth regulating factor 4, copper superoxide dismutase,
      ubiquitin-protein ligase and plantacyanin respectively. RESULTS: The findings
      showed that the overexpression of 6 miRNAs at 24, 48 and 72 h after infection
      resulted in the repression of their target genes and the expression of 2 miRNAs
      didn't affect their target genes. CONCLUSION: These results provide the first
      indication of the miRNAs role in response to the infection of Pcc in A. thaliana
      and open new vistas for a better understanding of miRNA regulation of plant
      response to Pcc.

PMID- 29023007
TI  - Optimization of Culture Medium for the Growth of Candida sp. and Blastobotrys sp.
      as Starter Culture in Fermentation of Cocoa Beans (Theobroma cacao) Using
      Response Surface Methodology (RSM).
AB  - BACKGROUND AND OBJECTIVE: Inoculation of starter culture in cocoa bean
      fermentation produces consistent, predictable and high quality of fermented cocoa
      beans. It is important to produce healthy inoculum in cocoa bean fermentation for
      better fermented products. Inoculum could minimize the length of the lag phase in
      fermentation. The purpose of this study was to optimize the component of culture
      medium for the maximum cultivation of Candida sp. and Blastobotrys sp. MATERIALS
      AND METHODS: Molasses and yeast extract were chosen as medium composition and
      Response Surface Methodology (RSM) was then employed to optimize the molasses and
      yeast extract. RESULTS: Maximum growth of Candida sp. (7.63 log CFU mL-1) and
      Blastobotrys sp. (8.30 log CFU mL-1) were obtained from the fermentation. Optimum
      culture media for the growth of Candida sp., consist of 10% (w/v) molasses and 2%
      (w/v) yeast extract, while for Blastobotrys sp., were 1.94% (w/v) molasses and 2%
      (w/v) yeast extract. CONCLUSION: This study shows that culture medium consists of
      molasses and yeast extract were able to produce maximum growth of Candida sp. and
      Blastobotrys sp., as a starter culture for cocoa bean fermentation.

PMID- 29023008
TI  - Aphid Species Affect Foraging Behavior of Coccinella septempunctata
      (Coccinellidae: Coleoptera).
AB  - BACKGROUND: Flowers are admirable in scenic good looks and artistic
      beautification. These are also playing necessary roles in therapeutic
      preparations. Aphid is an important sucking pest of various flowers in ornamental
      territories and it is generally controlled by predators, so it was necessary to
      evaluate which aphid species affect the predator more or less. MATERIALS AND
      METHODS: Biocontrol agent Coccinella septempunctata was used against cosmos aphid
      (Aphis spiraecola, rose aphid (Macrosiphum rosea), gul e ashrafi aphid (Aphis
      fabae), kaner aphid (Aphis nerii), chandni aphid (Sitobion avenae), dahlia aphid
      (Myzus persicae) and annual chrysanthemum aphid (Macrosiphoniella sanborni).
      RESULTS: The grub of C. septempunctata consumed 283.8+/-9.04 M. rosea, 487.7+/
      12.6 M. sanborni, 432.75+/-16.02 A. spiraecola, 478.2+/-8.07 A. fabae, 552.3+/
      9.04 M. persicae, 142+/-1.32 A. nerii and 498.5+/-13.09 S. avenae in its whole
      larval life. The M. persicae and M. rosea consuming grubs showed 100% adult
      emergence while, M. sanborni, A. spiraecola, A. fabae and S. avenae showed 96.58,
      89.02, 94.78 and 75.45% adult emergence, respectively. CONCLUSION: The C.
      septempunctata has significant predatory potential against A. spiraecola, M.
      rosea, A. fabae, S. avenae, M. persicae and M. sanborni except A. nerii. Thus,
      further studies are needed to find out alternate predator to control A. nerii on
      ornamentals.

PMID- 29023009
TI  - Myogenic Satellite Cells: Biological Milieu and Possible Clinical Applications.
AB  - Adult skeletal muscle is a post-mitotic terminally differentiated tissue that
      possesses an immense potential for regeneration after injury. This regeneration
      can be achieved by adult stem cells named satellite cells that inhabit the
      muscular tissue. These cells were first identified in 1961 and were described as
      being wedged between the plasma membrane of the muscle fiber and the surrounding
      basement membrane. Since their discovery, many researchers investigated their
      embryological origin and the exact role they play in muscle regeneration and
      repair. Under normal conditions, satellite cells are retained in a quiescent
      state and when required, these cells are activated to proliferate and
      differentiate to repair pre-existing muscle fibers or to a lesser extent fuse
      with each other to form new myofibers. During skeletal muscle regeneration,
      satellite cell actions are regulated through a cascade of complex signaling
      pathways that are influenced by multiple extrinsic factors within the satellite
      cell micro-environment. Here, the basic concepts were studied about satellite
      cells, their development, function, distribution and the different cellular and
      molecular mechanisms that regulate these cells. The recent findings about some of
      their clinical applications and potential therapeutic use were also discussed.

PMID- 29023010
TI  - Bio-controlling Effect of Leaf Extract of Tagetes patula L. (Marigold) on Growth
      Parameters and Diseases of Tomato.
AB  - BACKGROUND: The genus Tagetes (Asteraceae) is native to Americas but some of its
      members (in particular T. erecta and T. patula) commonly known as marigolds were
      naturalized in the old world (India, North Africa and Europe) as early as in 16th
      century. The flowers of French marigold (Tagetes patula L.) are widely used in
      folk medicine, in particular for treating inflammation-related disorders.
      MATERIALS AND METHODS: This study investigated the potential use of marigold
      (Tagetes patula L.) flower aqueous flower extract by spaying method on tomato
      plants on a weekly basis and the data of growth, yield and disease of tomato
      pants were observed from 10th day onwards under field condition. RESULTS: The
      marigold flower extract showed significant increase in shoot height, number of
      branches, number of leaves, number of buds, number of flowers and number of
      fruits of tomato plant, while significant reduction in various diseases of tomato
      plants over control at probability level ***p<0.001. The percentage of reduction
      of disease was calculated after the spray of marigold flower aqueous extract on
      plants. The marigold flower extract was found effectively in controlling canker
      (62.82%), early blight (61.53%), wilt (18.42%), fruit spot (27.41%), blossom end
      rot (50.43%) and sun scald (26.44%) in comparison to controls under field
      condition. CONCLUSION: The findings are in line with the bio-controlling
      properties of marigold preparations as bio-pesticide confirmed in growth and
      yield of tomato plants. Thus, marigold can contribute in reducing use of chemical
      pesticides and act as a good alternative to synthetic pesticides.

PMID- 29023011
TI  - Effect of AgNO3 and BAP on Root as a Novel Explant in Date Palm (Phoenix
      dactylifera cv. Medjool) Somatic Embryogenesis.
AB  - BACKGROUND AND OBJECTIVE: Somatic embryogenesis techniques are used for cloning a
      wide range of varieties of date palms around the world. The aim of the present
      study was to develop an efficient method with the lowest cost and the greatest
      potential to obtain in vitro plantlets of date palm cv. Medjool. Also, produce
      embryogenic callus and somatic embryos without using 2,4-dichlorophenoxyacetic
      acid (2,4-D). METHODOLOGY: In this study, produced plantlets through somatic
      embryogenesis were used in vitro roots as explant cultured on Murashige and Skoog
      (MS) media containing three level of Silver Nitrate (AgNO3) (0, 3 and 6 mg L-1)
      plus two level of 6-benzylaminopurine (BAP) (0 and 2 mg L-1) plus 0.1 mg L-1 1
      naphthylacetic acid (NAA) for callus induction. After 12 weeks of culture, callus
      induction and after 16 weeks, production of embryogenic callus and embryos were
      occurred from root explants. RESULTS: According to the results, medium containing
      2 mg L-1 BAP and 3 mg L-1 silver nitrate+0.1 mg L-1 NAA showed the highest amount
      of embryogenic callus fresh weight (1.38 g). This treatment also cause the
      highest number and length of embryos by production of 90.04 embryogenic callus
      with length of 11.18 mm. On the other hand, shoots were appeared from germinated
      embryos and white roots began to appear within 8 weeks. Medium contains 3 mg L-1
      BAP and 0.1 mg L-1 NAA with average of 12.27 cm shoot length and 15.48 cm root
      length was the best. Control treatment had the lowest average shoot (3.71 cm) and
      root (5.03 cm) length. CONCLUSION: This study showed that certain concentration
      of silver nitrate and BAP has stimulating effect on growth of produced embryonic
      callus from root segments of Medjool cultivar of date palm.

PMID- 29023012
TI  - Levels of Blood Glucose and Insulin Expression of Beta-cells in Streptozotocin
      induced Diabetic Rats Treated with Ethanolic Extract of Artocarpus altilis Leaves
      and GABA.
AB  - BACKGROUND AND OBJECTIVE: Information about the Artocarpus altilis leaf as an
      antidiabetic associated with the active compounds Gamma Amino Butyric Acid (GABA)
      is still limited. This study was conducted to determine the effects of ethanolic
      extract of A. altilis leaves decoction and GABA on blood glucose levels and
      insulin expression of beta-cells in streptozotocin-induced diabetic rats.
      MATERIAL AND METHODS: This study was done by using completely randomized design
      and male Sprague Dewley rats. The rats were devided into normal control group and
      diabetic rats groups. Levels of bood glucose were measured using strip rapid
      test. The insulin expression in beta-cells was assessed using
      immunohistochemistry. Quantitative data were analyzed using ANOVA at 5%
      confidence level. RESULTS: The result indicated that 50 mg k-1 b.wt., GABA, 400
      and 800 mg k-1 b.wt., ethanolic extract of A. altilis leaves decreased the level
      of blood glucose and increased the insulin expression in pancreas beta-cells.
      CONCLUSION: The GABA and ethanolic extract of A. altilis leaves with a minimum
      dose of 400 mg k-1 b.wt., can be used as an antidiabetic. Pancreas is the target
      organ was affected by GABA and A. altilis leaves as antidiabetic agents. Results
      of this study may support the development of research on the potency of GABA in
      natural materials as antidiabetic particularly type 1 diabetes.

PMID- 29023013
TI  - Anti-proliferation and Apoptosis Induction of Aqueous Leaf Extract of Carica
      papaya L. on Human Breast Cancer Cells MCF-7.
AB  - BACKGROUND AND OBJECTIVE: Breast cancer is the most frequently diagnosed cancer
      in women. Chemotherapy is the main method of breast cancer treatment but there
      are side effects. Carica papaya leaves is vegetable foods consumed by most people
      of Indonesia have potential as anticancer. The aim of this study was to
      investigate anti-proliferative and apoptotic induced effect of aqueous papaya
      leaves extracts on human breast cancer cell lines MCF-7. MATERIALS AND METHODS:
      Inhibitory on cell proliferation was measured by MTT assay while apoptosis
      induction was measured using Annexin V. RESULTS: The results showed that papaya
      leaf can inhibit the proliferation of human breast cancer cells MCF-7 with IC50
      in 1319.25 MUg mL-1. The IC50 values of papaya leaf extract was higher than the
      IC50 value quercetin and doxorubicin. Papaya leaf extract can also induce
      apoptosis of breast cancer cells MCF-7 about 22.54% for concentration 659.63 MUg
      mL-1 and about 20.73% for concentration 329.81 MUg mL-1. The percentage of cell
      apoptosis of papaya leaf extract lower than doxorubicin but higher than
      quercetin. CONCLUSION: This study indicated that papaya leaf extract have
      potential as anticancer through mechanism anti-proliferation and apoptosis
      induction.

PMID- 29023014
TI  - Influence of Grand Multiparity on the Levels of Insulin, Glucose and HOMA-IR in
      Comparison with Nulliparity and Primiparity.
AB  - OBJECTIVE: It is to compare the levels of fasting glucose and insulin as well as
      insulin resistance in grand multiparas with primiparity and nulliparity.
      METHODOLOGY: Fasting blood samples were collected from 100 non-pregnant ladies as
      control group, 100 primiparity pregnant women and 100 grand multiparity pregnant
      women. Glucose (FBS) and insulin (FSI) concentrations were measured by Hitachi
      912 full automated Chemistry Analyzer (Roche Diagnostics, Germany) as
      manufacturer procedure. Insulin resistance was calculated following the formula:
      FBG (mg dL-1)*FSI (MUU mL-1)/405. RESULTS: This study found a significant
      reduction in glucose level in primiparity when compared to control group but it
      was increased significantly in multiparity comparing to primiparity and control.
      Insulin level showed significant high concentrations in pregnant women and
      increased significantly in grand multiparas comparing to primiparas and controls.
      As a result of that, HOMA-IR was increased significantly by increasing of parity.
      Also, there was a significant increase in fasting insulin and a decrease in
      insulin sensitivity with parity with association to age and obesity. CONCLUSION:
      Grand multiparity is associated with an increased risk of subsequent clinical
      insulin resistance (HOMA-IR).

PMID- 29023016
TI  - Indigenous Halomonas spp., the Potential Nitrifying Bacteria for Saline Ammonium
      Waste Water Treatment.
AB  - BACKGROUND AND OBJECTIVE: Toxic nitrogen compounds are one cause decreasing of
      shrimp production and water pollution. Indigenous Halomonas spp., isolated from
      Pacific white shrimp farm are benefitted for saline ammonium waste water
      treatment. This study aimed to isolate the heterotrophic-halophilic Halomonas
      spp. and investigate their ammonium removal efficiency. MATERIALS AND METHODS:
      Halomonas spp., were isolated by culturing of samples collected from shrimp farm
      into modified Pep-Beef-AOM medium. Ammonium converting ability was tested and
      monitored by nitrite reagent. Ammonium removal efficiency was measured by the
      standard colorimetric method. Identification and classification of Halomonas
      spp., were studied by morphological, physiological and biochemical
      characteristics as well as molecular information. RESULTS: There were 5 strains
      of heterotrophic-halophilic nitrifying bacteria including SKNB2, SKNB4, SKNB17,
      SKNB20 and SKNB22 were isolated. The identification result based on 16S rRNA
      sequence analysis indicated that all 5 strains were Halomonas spp., with sequence
      similarity values of 91-99 %. Ammonium removal efficiency of all strains showed a
      range of 23-71%. The production of nitrite was low detected of 0.01-0.15 mg-N L
      1, while the amount of nitrate was almost undetectable. CONCLUSION: This might
      suggest that the indigenous Halomonas spp., as nitrifying bacteria involved
      biological nitrification process for decreasing and transforming of ammonia. Due
      to being heterotrophic, halophilic and ammonium removing bacteria, these
      Halomonas spp., could be developed for use in treatment of saline ammonium waste
      water.

PMID- 29023015
TI  - Evaluation of Growth Performances of Some Locally Farmed Maize (Zea mays L.) in
      Cross River State, Nigeria under Different Concentrations of Silicon.
AB  - OBJECTIVE: Growth performances of four maize varieties (91 SUWANI, TZL COMP 4, DT
      STR Y SYN 2 and IWO SYN C2) were investigated at four levels of silicon
      concentration (0, 2500, 5000 and 7500 mg, with 0 mg as control). METHODOLOGY:
      Viable seeds were planted in polythene bags (64 bags) containing soil in a
      randomized complete block design (a 4*4 factorial experiment) with four
      replications. Plant height, stem girth, leaf area and leaf number were evaluated
      at 4, 6, 8 and 10 weeks after planting. RESULTS: There was significant difference
      (p<=0.05) for all growth parameters and across varieties. Highest mean plant
      height (144.58 cm) and mean number of leaves (12.23) were recorded at 5000 mg
      silicon concentration in all varieties, while stem girth and stem biomass were
      highest in TZL COMP4 (3.42 cm, 38.44 dry weight g-1). CONCLUSION: Based on these
      results, 5000 mg silicon concentration is recommended as nutrient supplement to
      enhance maize production.

PMID- 29023017
TI  - Effect of Temporal Pattern of Radiation in Intensity Modulated Radiotherapy on
      Cell Cycle Progression and Apoptosis of ACHN Renal Cell Carcinoma Cell Line.
AB  - BACKGROUND AND OBJECTIVE: The existence of a hypersensitive radiation response to
      doses below 1 Gy is well established for many normal and tumor cell lines. The
      aim of this study was to ascertain the impact of temporal pattern modeling IMRT
      on survival, cell cycle and apoptosis of human RCC cell line ACHN, so as to
      provide radiobiological basis for optimizing IMRT plans for this disease.
      MATERIALS AND METHODS: The ACHN renal cell carcinoma cell line was used in this
      study. Impact of the triangle, V, small-large or large-small temporal patterns in
      the presence and absence of threshold dose of hyper-radiosensitivity at the
      beginning of patterns were studied using soft agarclonogenic assays. Cell cycle
      and apoptosis analysis were performed after irradiation with the temporal
      patterns. RESULTS: For triangle and small-large dose sequences, survival fraction
      was significantly reduced after irradiation with or without threshold dose of
      hyper-radiosensitivity at the beginning of the patterns. In all of the dose
      patterns, cell cycle distributions and the percentage of apoptotic cells at 24 h
      after irradiation with or without priming dose of hyper-radiosensitivity showed
      no significant difference. However, apoptotic cells were increased when beams
      with the smallest dose applied at the beginning of dose pattern like triangle and
      small-large dose sequence. CONCLUSION: These data show that the biologic effects
      of single fraction may differ in clinical settings depending on the size and
      sequence of the partial fractions. Doses at the beginning but not at the end of
      sequences may change cytotoxicity effects of radiation.

PMID- 29023018
TI  - Akt Signal Transduction Pathways and Nuclear Factor-kappa B (NF-kappaB)
      Transcription as a Molecular Target of Oral Tongue Squamous Cell Carcinoma (SP
      C1) Using Papua's Anthill Plant ( Myrmecodia pendans ).
AB  - BACKGROUND AND OBJECTIVE: Squamous cell carcinoma is a malignant tumor derived
      from epithelial tissue with cell structure group, capable to infiltrate through
      the bloodstream and lymphatic tissue, spreading throughout the body. This study
      aim to complete theoretical foundation of flavonoid compound from anthill plant
      (Myrmecodia pendans) which contribute in growing cell line oral tongue squamous
      cell carcinoma through proliferation inhibition, inhibition mechanism
      transduction Akt signal and NF-kappaB in tongue cancer cell Supri's-clone (SP
      C1). Application benefit to explore potential fractionation anthill plant use
      herbal ingredients for chemo protective therapy. MATERIALS AND METHODS: This
      whole study conducted with experiment laboratorium method utilized tongue cancer
      human cell SP-C1. This study consist 2 steps, first to determinate, extraction
      and fractionation anthill plant and carry out tonicity test to get flavonoid
      fraction from anthill plant which has anticancer potential against tongue cancer
      cell SP-C1. The second stage held with invasion inhibition test, proliferation
      and inhibition test against protein Akt expression and NF-kappaB in tongue cancer
      cell SP-C1. The barriers to proliferation through the test of MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, barriers to
      invasion through Boyden chamber assay and the membrane polycarbonate, ELISA
      analysis and Western blotting analysis on the obstacle Akt signal transduction
      pathways and transcription factor of nuclear factor-kappa B (NF-kappaB). Data
      analysis conducted with 2 way ANOVA followed with LSD post hoc test with
      significance is set on 95%. Pearson correlation conduct to find strong
      relationship intervariable. RESULTS: This study showed that the average cell
      growth inhibition SP-C1 based on the time and concentration using the MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The resistance of
      cancer cell in vitro SP-C1. On ELISA testing and Western blotting analysis,
      inhibiton of protein expression of Akt signal transduction and transcription
      factor of nuclear factor-kappa B (NF-kappaB) showed increased protein expression
      was significantly obstacles and prove that the ethyl acetate fraction flavonoid
      inhibits translocation and activation of transcription pathway NF-kappaB and
      growth factors that induces the phosphorylation of Akt signal transduction
      pathway. CONCLUSION: Ethyl acetate fraction flavonoid anthill has antitumor
      activity in multiple molecular targets transduction pathway including Akt and
      nuclear factor-kappa B (NF-kappaB) squamous cell carcinoma of the tongue.

PMID- 29023019
TI  - Stress Levels, Mortality, Intestinal Morphometry and Histomorphology of Chabro
      Broiler Birds Subjected to Varying Degrees of Post Hatch Delay in Feeding.
AB  - BACKGROUND AND OBJECTIVE: Kashmir is a part of Jammu and Kashmir State of India
      where a large chunk of day old chicks are procured from outside the state and
      these chicks are transported across a distance of hundreds of kilometers over a
      period of several days. The long distance transport without any access to feed
      not only subjects the birds to early life stress but also affects their gut
      morphological development. Therefore, a study was conducted to evaluate the
      effect of delayed feeding on stress levels, mortality, intestinal morphometry and
      histomorphology of chabro broiler chicken. MATERIALS AND METHODS: A total of 400
      day old chabro chicks were randomly divided into 5 groups, each group comprising
      of four replicates of 20 birds. Chicks allotted to group-1 (G 1) were offered
      feed at hatchery itself whereas feeding in groups G 2, G 3, G 4 and G 5 were
      initiated at the farm after the delay of 12, 24, 48 and 72 h, respectively.
      RESULTS: The results revealed that the heterophil count showed a steady increase
      from G 1-G 5 and significantly (p<0.05) higher count was found in G 3, G 4 and G
      5 compared to G 1. However, the lymphocyte count showed a steady decrease as
      delay in feeding increased. H:L ratio followed a regular increase from G 1-G 5
      and was significantly (p<0.05) higher in G 3, G 4 and G 5 compared to G 1. An
      overall mortality of 13% was recorded during the trial and all of it occurred
      during first 2 weeks. The highest overall mortality of 22.50+/-3.23% was recorded
      in group G 5 followed by 17.50+/-6.61% in G 4. The villus height of duodenum and
      jejunum was significantly (p<0.05) higher in G 2, G 3, G 4 and G 5 as compared to
      G 1. Crypt depth and muscular is thickness of duodenum was significantly (p>0.05)
      lower in G 4 and G 5 compared to G 1. CONCLUSION: The duration of post hatch
      feeding delay gradually increased the stress level and mortality of birds and
      also decreased the length of different segments of small intestine in birds. No
      adverse effect on histomorphology was observed at the end of trial. Feeding at
      hatchery itself or feeding during transportation of birds would be a viable
      strategy to overcome the negative effects of delayed feeding in chicken.

PMID- 29023020
TI  - Effect of Genetic Polymorphisms in GH/Hpa II and MSTN / Dra I Loci on Body Weight
      in Friesian Bull Calves.
AB  - OBJECTIVE: The GH and MSTN gene polymorphisms and their association with body
      weight were declared in a population of 100 Friesian bull calves. MATERIALS AND
      METHODS: For DNA extraction, collection of blood samples was carried out from the
      studied animals. The PCR for GH and MSTN genes yielded fragments of 329 and 1346
      bp, respectively. RESULTS: The PCR-HpaII digestion of 329 bp of GH gene revealed
      three genotypes: AA genotype possess undigested fragment (329 bp), AB genotype
      has three fragments (329, 224 and 105 bp) and BB genotype has two fragments (224
      and 105 bp). The GH genotypes incidence and alleles frequency were calculated.
      For the 100 Friesian bull calves, genotypic frequencies for the AA, AB and BB
      genotypes were 0.1, 0.78 and 0.12, respectively and the allele frequencies for A
      and B allele frequencies were 0.49 and 0.51. Statistical analysis revealed that
      there was a significant effect of GH genotypes on body weight. The AB genotype
      possessed higher body weight than the other 2 genotypes. Regarding MSTN gene, PCR
      DraI digestion of 1346 bp fragment was monomorphic; where it yielded four
      fragments (505, 427, 321 and 93 bp) in all animals under study. CONCLUSION: The
      outcome of this study is that it highlights the effectiveness of GH/HpaII locus
      as candidate marker for body weight in cattle rather than MSTN/DraI.

PMID- 29023021
TI  - Effect of Allogeneic Bone Marrow-mesenchymal Stem Cells (BM-MSCs) to Accelerate
      Burn Healing of Rat on the Expression of Collagen Type I and Integrin
      alpha2beta1.
AB  - BACKGROUND AND OBJECTIVE: Burn is a public health problem, it causes physical
      disability even death. Treatment of burn wound has been conducted in various
      ways, but the satisfactory healing has not been provided. Bone marrow-derived
      mesenchymal stem cells (BM-MSCs) treatment is one of attempt to burn recovery,
      accelerate wound healing and angiogenesis. This study aimed to investigate the
      effect of allogeneic BM-MSC treatment on the expression of collagen type I and
      integrin alpha2beta1 in burn skin tissue of rat observed on day 14. MATERIALS AND
      METHODS: Twelve Wistar rats divided into two groups, control group (injected with
      phospate buffer solution) and treatment group (injected with BM-MSC). Rat was
      anaesthetized with xylazine and ketamine (ratio 1:1), fur of rat's back was
      shaved and full thickness burn was made by boiling plate in hot water for 30 min
      and patched on the back for 20 min. The burns were covered by tegaderm film and
      elastomult haft. Antalgin as an analgetic was injected to rats during observation
      process. Burns of rat was observed on day 14. In this study one-way analysis of
      variance test and Tukey as a further test were analyzed. RESULTS: The results
      showed that the healing time of allogeneic BM-MSC treatment on burn skin tissue
      rats was faster, the thickness of collagen type I in burn skin tissue of rats was
      thicker (0.977 MUm) than controls (0.475 MUm) and statistically demonstrated
      significant differences (p = 0.000). The average percentage of integrin
      alpha2beta1 expression was higher (2.94%) than control group (2.34%), but the
      differences were not statistically significant (p = 0.176). CONCLUSION: The study
      concluded that BM-MSC treatment was able to accelerate the healing process of
      burns by increasing the thickness of the collagen and the percentage of integrin
      alpha2beta1, thus accelerated the cell migration involved during wound healing.

PMID- 29023022
TI  - A Trial Diagnosis of Ascites Syndrome in Broiler Chickens.
AB  - BACKGROUND: Ascites syndrome is currently a serious disease issue for the global
      chicken industry. Ascites syndrome is a metabolic disorder frequently found in
      fast growing broilers including abdominal distention and standing fluid
      collection in chicken abdomen. It is one of the most common nutrition metabolic
      disorders. MATERIALS AND METHODS: In this study, the clinical diagnosis
      technology of broiler ascites symptoms mainly included the trial inquiry of
      feeders and administrators, local observation, detection of farm gas and faeces
      and pathological autopsy. RESULTS: The study investigated the case of broiler
      ascites syndrome of local commercial broiler chickens at the age of 4-5 weeks to
      reduce outburst of ascites syndrome in broiler chickens. Through the trial
      clinical diagnosis of broiler ascites symptoms and pathological autopsy and
      observation, it came to the definite diagnosis of broiler ascites. Subsequent
      investigation found that the rearing houses were closed and sealed with poor
      ventilation and a high breeding density and much ammonia gas. CONCLUSION: Under
      the comprehensive management and drug treatments, there were 800 chickens found
      ill and later came back to normal from illness after the treatments, except for
      the death of 38 sick chickens. The appetite and drink of broiler chicken came to
      normal gradually.

PMID- 29023023
TI  - Isolation, Purification and Characterization of Antimicrobial Agent Antagonistic
      to Escherichia coli ATCC 10536 Produced by Bacillus pumilus SAFR-032 Isolated
      from the Soil of Unaizah, Al Qassim Province of Saudi Arabia.
AB  - BACKGROUND: Escherichia coli is one of the most common pathogenic bacteria, which
      cause urinary tract infections in infants as well as in adult human beings. Due
      to the emergence of antibiotic resistance in E. coli, there is a great demand of
      new antimicrobial agent for the treatment of infections caused by such E. coli.
      This study aims to isolate, identify and characterize the native soil-bacterial
      strains predominate in the soil of Unaizah city, which produce antimicrobial
      agent antagonistic to E. coli ATCC 10536, followed by isolation, purification and
      characterization of antimicrobial agent. MATERIALS AND METHODS: Pour plate,
      spread plate and 16S rRNA sequence analysis methods were followed for the
      isolation and identification of soil bacteria. Ammonium sulphate and dialysis
      (MWCO-8 KD) methods were followed for the isolation and partial purification of
      antimicrobial agent from the cell free broths. The characterization of
      antimicrobial agent was carried out by determining the minimum inhibitory
      concentration and effects of temperature and pH on the antimicrobial stability.
      RESULTS: Out of the twenty five soil samples, only one soil-bacterial strain was
      found to produce antimicrobial agent antagonistic to E. coli ATCC 10536. The
      isolated soil bacterium was identified as Bacillus pumilus SAFR-032. The soil
      isolate was characterized and results suggest that 30 degrees C temperature and
      pH 7.0 were the optimum growth parameters and soybean casein digest broth was the
      best fermentation medium, whereas the highest production of antimicrobial agent
      was at 35 degrees C temperature, pH 7.0, shaking at 150-220 rpm and at 60th h of
      incubation. The maximum yield of antimicrobial agent was obtained at 60% of (NH
      4) 2SO 4. The results of characterization of antimicrobial agent suggest that the
      maximum and minimum antimicrobial activities were at pH 3.0 and 8.0,
      respectively, whereas antimicrobial activity was unaffected by temperature. The
      antimicrobial agent was highly stable at varying range of temperature 50-120
      degrees C. Minimum inhibitory concentration of antimicrobial agent was found to
      be 64 MUg mL -1. CONCLUSION: In conclusion, this study might be a great endeavor
      for the healthcare industry in order to treatment of different infections caused
      by E. coli and that warrants further investigations to fully standardized and
      establish the antimicrobial profile of effect(s) of this isolate.

PMID- 29023024
TI  - Diversity of Butterflies (Lepidoptera) in Manembo-Nembo Wildlife Reserve, North
      Sulawesi, Indonesia.
AB  - BACKGROUND AND OBJECTIVE: The degradation of a habitat will affect the population
      of butterflies living in it. This study aims to analyse the diversity of
      butterflies in the area of Manembo-Nembo Wildlife Reserve, North Sulawesi.
      MATERIALS AND METHODS: Employing purposive sampling, the study was conducted for
      five months. The collection of butterflies was done by using the sweeping
      technique, following the transect line applied randomly along 1000 m to three
      types of habitat (the primary forest, riverside in the forest and agricultural
      land). The species diversity was determined by using diversity index (Shannon
      Wiener). RESULTS: The study identified 4 families, 44 species and 748 individual
      butterflies. Nymphalidae was a family predominantly found (71.12%), while the
      species mostly found was Ideopsis juventa tontoliensis (10.16%). Abundance
      (76.50), richness (20.25), diversity (2.66) and species evenness (0.88) were
      mostly found in riverside habitats in the forest, while the lowest was found in
      the primary forest. The similarities of butterfly communities in the different
      types of habitats indicate that the highest similarity index of butterfly
      communities is in the habitats of the primary forest and riverside in the forest
      wi a value of 80%. CONCLUSION: The highest diversity of butterflies in all types
      of habitats found in riverside. MAIN CONCLUSION: The high diversity of
      butterflies in the river is strongly influenced by the presence of vegetation as
      food and host plants of butterflies and this habitat should be conserved for the
      survival of the butterfly in a wildlife reserve Manembo-Nembo, North Sulawesi. It
      is expected that the results of this study could become important data of the
      diversity of butterflies and effects of changes of habitats on the diversity of
      butterflies in Manembo-Nembo Wildlife Reserve, North Sulawesi.

PMID- 29023025
TI  - Hypoglycemic and Hypolipidemic Effects of Seed Extract from Antidesma bunius (L.)
      Spreng in Streptozotocin-induced Diabetic Rats.
AB  - BACKGROUND: Antidesma bunius (L.) Spreng has been reported to possess various
      beneficial medicinal properties. Scientific information about this plant is
      limited. This study was therefore, designed to determine hypoglycaemic and
      hypolipidemic effects of ethanol seed extract from A. bunius (ABSE). Antioxidant
      activity and also acute toxicity were conducted. METHODOLOGY: The hypoglycaemic
      and hypolipidemic effects were studied by oral giving ABSE at a dose of 250 mg kg
      -1 to streptozotocin-induced diabetic rats daily for 6 weeks. Antioxidant
      activity was studied using DPPH assay. The ABSE at the doses of 500, 1000, 1500
      and 2000 mg kg -1 were employed in the acute toxicity study. RESULTS: The results
      revealed that ABSE significantly (p<0.05) reduced the blood glucose level and
      recovered the pathology of hematological values, but significantly (p<0.05)
      increased the body weight and slightly increased serum insulin of the diabetic
      rats. However, ABSE recovered pathology of hematological values, but affected
      renal and hepatic functions in the treated rats by producing an alteration of
      creatinine, albumin, total protein, BUN and ALP. Interestingly, ABSE increased
      WBC and HDL, but reduced CHOL, LDL and TG both in normal and diabetic ABSE
      treated rats. The ABSE possessed relatively low antioxidant activity with IC50 of
      2174+/-14.24 mg mL -1 compared to vitamin C (1.48+/-0.07 MUg mL -1). Fortunately,
      ABSE did not produce any symptoms of acute toxicity and mortality in the rats.
      CONCLUSION: The ethanol seed extract from A. bunius possesses hypoglycemic and
      hypolipidemic effects. The ABSE also recovered the pathology of the hematology
      but may cause renal dysfunction in the diabetic rats. The hypoglycemic and
      hypolipidemic effects are likely due to its antioxidant and insulin secretion
      activities.

PMID- 29023026
TI  - Effect of Water Salinity on the External Morphology of Ovarian Maturation Stages
      of Orange Mud Crab, Scylla olivacea (Herbst, 1796) in Captivity.
AB  - BACKGROUND AND OBJECTIVE: Mud crab from the genus Scylla are considered as one of
      the most demanded seafood items nowadays as their flesh has high quality, tasty
      and higher growth rate thus support and boosted expansion in aquaculture sector
      especially in Malaysia. Present study was designed to focus on the effect of
      water salinity on the ovarian maturation of orange mud crab, Scylla olivacea
      based on morphological characteristics. METHODOLOGY: Samples were collected from
      Setiu wetlands, Terengganu, Malaysia from July-September, 2015. Ovarian
      maturation of S. olivacea was classified into four stages based on previous study
      which were: Immature (Stage 1), early mature (Stage 2), late mature (Stage 3) and
      fully mature (Stage 4). RESULTS: Morphologically as the ovary develop the
      colouration start to change from translucent or whitish in colour and sometimes
      creamy to pale yellow, follow by light orange and lastly reddish orange. Stage 1
      ovary was translucent and whitish in colour, stage 2 ovary was pale yellow in
      colour, stage 3 was light orange and stage 4 ovary was reddish orange in colour.
      Gonad Somatic Index (GSI) of S. olivacea remained low at stage 1 and 2 and began
      to increase started at stage 3. This present study involved three different
      salinities treatments, which treatment 1 (10 ppt), treatment 2 (20 ppt) and
      treatment 3 (30 ppt). Treatment 2 produce the highest number of stage 4 ovarian
      maturation based on colouration and the highest GSI recorded, follow by treatment
      1 and lastly treatment 3. CONCLUSION: This present study proved that salinity
      does affected the ovarian maturation of S. olivacea in captivity and provides
      important information regarding the effect of water salinity on ovarian
      maturation for further studies on reproductive biology of this species.

PMID- 29023027
TI  - Influence of L-carnitine on the Expression Level of Adipose Tissue miRNAs Related
      to Weight Changes in Obese Rats.
AB  - BACKGROUND AND OBJECTIVE: Molecular mechanisms of most anti-obesity drugs are
      remained to be clear. MicroRNAs that are noncoding RNA molecules supposed to
      regulate biological processes concomitant to obesity and have attracted a lot of
      attention to themselves. The miR-27a and miR-143 expression levels in obese and
      non-obese rats during weight changes and L-carnitine (LC) effects on them was
      investigated in this study. MATERIALS AND METHODS: In the present study 12 male
      Wistar rats were randomly divided into normal fat diet and high fat diet groups
      to develop obesity. After 8 weeks rats were weighted and half of diet induced
      obese rats were randomly selected to receive 200 mg LC kg -1 b.wt. for 4 weeks.
      At the end epididymal fat was isolated to investigate expression level of
      microRNAs by real-time PCR. RESULTS: After 12 weeks, high fat diet in comparison
      with normal fat diet mediated significant decrease and increase in expression
      levels of miR-27a and miR-143 , respectively. These changes were modified in
      groups, which had received LC in a 4 weeks period. Furthermore, rats in this
      group gained less weight. CONCLUSION: Findings of this study suggest that the
      changes of microRNAs expression probably play a role in pathogenesis of obesity,
      might be modulated by means of dietary agents and supplements and modify weight
      gain trend.

PMID- 29023028
TI  - Methicillin-resistant Staphylococcus aureus Nasal Carriage Among Patients
      Admitted at Shaqra General Hospital in Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) have
      been causing increasing problems in hospitals and nursing homes worldwide.
      Limited number of studies in Saudi Arabia has attempted to investigate infection
      and risk factors associated with nosocomial acquired MRSA. The present study was
      undertaken to determine the occurrence, prevalence, antibiotic susceptibility
      pattern and genetic characteristics of MRSA among admitted cases at Shaqra
      General Hospital (Saudi Arabia). METHODOLOGY: This study was conducted from
      October, 2014 to March, 2015. Nasal swabs were taken from 220 patients (105 males
      and 115 females) admitted at Shaqra General Hospital. The isolates were
      identified as S. aureus based on morphology, Gram stain, catalase test, coagulase
      test and mannitol salt agar fermentation. Antibiotic susceptibility testing of
      MRSA was performed with standard disk diffusion method. All methicillin-resistant
      isolates were examined for the existence of the mecA gene by PCR technique.
      RESULTS: Of the 220 patients, 90 (40.91%) were found to be nasal carriers of S.
      aureus. Among these 90 S. aureus isolates, 48 (21.82%) were MRSA. A statistically
      significant difference was only found for antibiotics usage between those with
      and without MRSA colonization. Antibiotic susceptibility pattern of isolated MRSA
      showed high susceptibility to vancomycin, linezolid, rifampicin, teicoplanin,
      complete resistance to penicillin, ampicillin, oxacillin and cefoxitin and
      intermediate resistance to amikacin, ciprofloxacin, teicoplanin, tetracycline and
      vancomycin. CONCLUSION: A high prevalence of multidrug-resistant MRSA nasal
      carriage was found. The identification of MRSA carriers is a step towards
      establishing a control policy for MRSA and helps to identify measures needed to
      reduce colonization pressure.

PMID- 29023029
TI  - Lysine and Glutamic Acids as the End Products of Multi-response of Optimized
      Fermented Medium by Mucor mucedo KP736529.
AB  - BACKGROUND: Amino acids are important for living organisms, they acting as
      crucial for metabolic activities and energy generation, wherein the deficiency in
      these amino acids cause various physiological defects. OBJECTIVE: The aim of this
      study is to investigate the effect of some nutritional factors on the amino acids
      production by Mucor mucedo KP736529 during fermentation intervals. METHODOLOGY:
      Mucor mucedo KP736529 was selected according to proteolytic activity. Corn steep
      liquor and olive cake were used in the fermented medium during Placket-Burman and
      central composite design to maximize the production of lysine and glutamic acids.
      RESULTS: During the screening by Plackett-Burman design, olive cake and Corn
      Steep Liquor (CSL) had potential importance for the higher production of amino
      acids. The individual fractionation of total amino acids showed both lysine and
      glutamic as the major amino acids associated with the fermentation process.
      Moreover, the Central Composite Design (CCD) has been adopted to explain the
      interaction between olive cake and CSL on the production of lysine and glutamic
      acids. The model recorded significant F-value, with high values of R 2, adjusted
      R 2 and predicted R 2 for both lysine and glutamic, indicating the validity of
      the data. Solving equation for maximum production of lysine recorded theoretical
      levels of olive cake and CSL, being 2.58 and 1.83 g L -1, respectively, with
      predicting value of lysine at 1.470 MUg mL -1, whereas the predicting value of
      glutamic acid reached 0.805 mg mL -1 at levels of 2.49 and 1.93 g L -1 from olive
      cake and CSL, respectively. The desirability function (D) showed the actual
      responses being 1.473+/-0.009 and 0.801+/-0.004 MUg mL -1 for lysine and glutamic
      acids, respectively. CONCLUSION: The model showed adequate validity to be applied
      in a large-scale production of both lysine and glutamic acids.

PMID- 29023030
TI  - Biological Activity Alterations of Human Amniotic Membrane Pre and Post
      Irradiation Tissue Banking.
AB  - BACKGROUND AND OBJECTIVE: Innate immunity of Human Amniotic Membrane (HAM) and
      its highly active secretome that rich with various types of growth factors and
      anti-inflammatory substances proposed it as a promising material for many medical
      studies and applications. METHODOLOGY: This study evaluate the biological
      activity of cultivated HAM pre and post tissue banking process in which freeze
      dried HAM was sterilized by 25 KGray (kGy) dose of gamma radiation. The HAM's
      antimicrobial activity, viability, growth of isolated human amniotic epithelial
      cells (HAECs), hematopoietic stimulation of co-cultivated murine bone marrow
      cells (mammalian model), scaffold efficiency for fish brain building up (non
      mammalian model) and self re-epithelialization after trypsin denuding treatment
      were examined as supposed biological activity features. RESULTS: Native HAM
      revealed viability indications and was active to kill all tested microorganisms;
      6 bacterial species (3 Gram-positive and 3 Gram-negative) and Candida albicans as
      a pathogenic fungus. Also, HAM activity promoted colony formation of murine
      hematopoietic cells, Tilapia nilotica brain fragment building-up and self re
      epithelialization after trypsin treatment. In contrary, radiation-based tissue
      banking of HAM caused HAM cellular death and consequently lacked almost all of
      examined biological activity features. CONCLUSION: Viable HAM was featured with
      biological activity than fixed HAM prepared by irradiation tissue banking.

PMID- 29023031
TI  - Growth Effect of Cinnamomum kanehirae Cuttings Associated with its Dark Septate
      Endophytes.
AB  - BACKGROUND AND OBJECTIVE: Stout camphor tree (Cinnamomum kanehirae Hay.) is an
      endemic specie in Taiwan and cutting is the major propagation of C. kanehirae for
      plantation. Mycorrhiza can accelerate the growth of the host plant, especially in
      root of the host plant. The objective of this study was to investigate the growth
      effect of the 2 dark septate endophytes isolated from C. kanehirae. MATERIALS AND
      METHODS: To measure the effects of stains CkDB2 and CkDB5 on growth performance
      of cuttings, the cuttings were carefully removed from their substrate after 9
      months of incubation. Each treatment had three replicates. RESULTS: After 9 month
      incubation, the mycorrhizal synthesis experiment showed that the roots of
      synthesized cuttings produced microsclerotia, a characteristic of dark septate
      endophyte, but nothing was found in the control. All inoculated cuttings had
      higher values of net height growth, dry weight, leaf area and chlorophyll
      concentration than the control. CONCLUSION: This study demonstrated that the 2
      endophytes, strains CkDB2 and CkDB5, capable of forming microsclerotia with C.
      kanehirae cuttings were dark septate endophytes. Based on the results, CkDB5 had
      a better growth response than CkDB2. Cuttings inoculated with CkDB5 showed a 200%
      increase in the root dry weight and therefore, CkDB5 could presumably be a
      prerequisite for the survival of C. kanehirae cutting plantation.

PMID- 29023032
TI  - Oncogenic Human Papillomavirus Infection and Genotype Characterization among
      Women in Orodara, Western Burkina Faso.
AB  - BACKGROUND AND OBJECTIVE: Cervical cancer usually occurs several years after
      persistent infection with oncogenic or high-risk human papillomavirus. The
      objective of this study was to determine carriage of 14 genotypes of high-risk
      human papillomavirus among women at Orodara and then characterize the genotypes
      found in these women. MATERIALS AND METHODS: From June to July 2015, 120 women
      from the general population were recruited in the health district of Orodara.
      They voluntarily agreed to participate in the study. Endocervical samples were
      taken from these women prior to screening for precancerous lesions by visual
      inspection with acetic acid and lugol's iodine. Identification of high-risk human
      papillomavirus genotype was done using real-time PCR. RESULTS: High-risk human
      papillomavirus prevalence was 38.3% and the most common genotypes were HPV 52
      (25.4%), HPV 33 (20.6%) and HPV 59 (11.1%). The HPV 66 was also identified with a
      prevalence of 9.5%. CONCLUSION: The HPV 16 and HPV 18 which are frequently
      associated with cancer worldwide were not found among the most frequent oncogenic
      HPV in women in Orodara.

PMID- 29023033
TI  - Genomics: A Way Forward to Tackle Climatic Challenges.

PMID- 29023034
TI  - Phenotypic and Molecular Characterization of Multidrug Resistant Klebsiella
      pneumoniae Isolated from Different Clinical Sources in Al-Najaf Province-Iraq.
AB  - BACKGROUND AND OBJECTIVE: Burns infections and urinary tract infections are the
      most important prevalent diseases in Asian countries, such as Iraq. Klebsiella
      pneumoniae is one of the most important bacteria cause this type of infections
      especially in hospitals. Therefore, the aim of this study was to investigate the
      prevalence of multi-drug resistance K. pneumoniae and extended-spectrum beta
      lactamases producing K. pneumoniae isolates from inpatients with urinary tract
      infection and burns infections in Al-Kufa hospital in Al-Najaf province, Iraq.
      MATERIALS AND METHODS: A total of 285 clinical samples were collected from in
      patients infected with urinary tract infection (141 urine samples) and burns
      infections (144 burns swabs). Fourteen different antibiotics were used by disc
      diffusion method and 13 antimicrobials resistance genes were used by PCR
      technique. RESULTS: A total of 43 K. pneumoniae strains were isolated. The
      highest resistance rate was observed for amoxicillin 25 MUg and
      amoxicillin+clavulanic acid 20+10 MUg (97.67%) while the lowest resistance rate
      was observed for imipenem 10 MUg (9.30%). The most common resistance associated
      genes were blaSHV (86.04%) and at lower prevalence were IMP (9.30%). CONCLUSION:
      Klebsiella pneumoniae strains isolated from burns infections were more virulent
      than those isolated from urinary tract infections.

PMID- 29023035
TI  - Cloning and Expression Analysis of HbPR-1b and HbPR-3 in Hevea brasiliensis
      During Inoculation with Rigidoporus microporus.
AB  - BACKGROUND AND OBJECTIVE: Pathogenesis-related (PR) proteins are dramatically
      accumulated after pathogen infection. Innate defense response through increasing
      PR-proteins is important for rubber rootstock selection that is tolerant to the
      white root disease caused by Rigidoporus microporus. This study was aimed to
      investigate the expression levels of PR-1 and PR-3 genes in tolerant (PB5/51) and
      susceptible (BPM24 and RRIM600) rubber clones after R. microporus infection.
      MATERIALS AND METHODS: The mRNA of HbPR-1b and HbPR-3 was isolated and
      characterized from rubber leaves. Gene expression levels of HbPR-1b and HbPR-3
      were compared among three rubber clones (PB5/51, BPM24 and RRIM600) after R.
      microporus infection at 0, 12, 24, 48, 72 and 96 h using quantitative real-time
      PCR. The relative transcript abundances between inoculated and control plants
      were compared using the means of gene expression between time points and by
      Tukey's HSD test. A probability value (p<0.05) was used to determine the
      significance of difference between time points. RESULTS: The open reading frame
      of HbPR-1b is 492 bp with deduced 163 amino acid residues and the phylogenetic
      analysis showed it shared significant evolutionary history and clustering into
      group I of PR-protein. Moreover, the partial HbPR-3 was isolated with 390 bp.
      Gene expression levels of HbPR-1b and HbPR-3 showed marked differences in both
      transcripts depending on the rubber clones. Two genes demonstrated up-regulation
      of both tolerance and susceptibility in response to attack by R. microporus. The
      highest expression levels were found in seedlings of PB5/51 after inoculation. In
      RRIM600, low expression levels of HbPR-1b and HbPR-3 were initially observed but
      gradually increased at 24 h post inoculation. The transcription profile of HbPR
      1b was stable expression in BPM24. CONCLUSION: The results demonstrated that the
      level ofHbPR-1b and HbPR-3 transcription can distinguish between tolerant and
      susceptible clones. The candidate defense genes to the white root disease were
      observed in PB5/51 seedlings, particularly HbPR-1b.

PMID- 29023036
TI  - Callus Induction from Various Organs of Dragon Fruit, Apple and Tomato on some
      Mediums.
AB  - BACKGROUND AND OBJECTIVE: Dragon fruit (Hylocereus spp.), apple (Malus sylvestris
      Mill.) and tomato (Solanum lycopersicum L.) are high potential sources of
      antioxidant compounds such as phenolics. The compounds have the capability of
      protecting cells and tissues against free radicals. Secondary metabolite produced
      by callus cell culture from plant organs also acts as a source of antioxidants.
      This study aimed to determine the optimal ratio of sucrose and 2,4-D in Murashige
      and Skoog (MS) medium for callus induction from different plant organ explants.
      With all of characteristic, callus can be used further for the development of
      natural cell regeneration agent. METHODOLOGY: This study was conducted using
      analytical technique. Suitable explants were obtained. They were developed in
      various concentrations of combination between MS medium and 2,4-D. Callus growth,
      including their weight and surface was then measured and analyzed by using one
      way analysis of variance (ANOVA). RESULTS: Callus was able to grow from its
      explants in 5-7 days after induction process. They were clear in color and had
      friable texture. The highest value of fresh weight of dragon fruit callus was
      obtained through MS supplemented with 1 MUL L-1 2,4-D and 30 g sucrose. However,
      apple and tomato callus induction and growth maintenance reached optimal medium
      on MS supplemented with 30 g sucrose and 2 MUL L-1 2,4-D. CONCLUSION: Callus of
      apple, dragon fruit and tomato was maintained upon MS supplemented with 30-40 g
      sucrose and 1-2 MUL L-1 2,4-D for optimum induction and growth. The optimization
      of growth medium will give advantages for further development of natural cell
      regeneration agent.

PMID- 29023037
TI  - Influence of Light Intensity and Photoperiod on the Seed Germination of Four
      Rhododendron Species in Taiwan.
AB  - BACKGROUND AND OBJECTIVE: There are 15 native Rhododendron species in Taiwan,
      among which 11 species are endemic and compose 73% of these native species.
      Although researchers predominantly use cuttings to propagate Rhododendron shrubs,
      there are no studies on the seed germination of Rhododendron species. The
      objective of this study was to evaluate the seed germination of four Rhododendron
      species in Taiwan under different light intensities and photoperiods. MATERIALS
      AND METHODS: Two experiments on the seed germination percentage of R.
      breviperulatum, R. kanehirai, R. ovatum and R. simsii were conducted in this
      study. The first experiment was to identify the seed germination percentage of
      these four Rhododendron species using different light intensities (0, 700, 1400
      and 3200 lux). The second experiment was to clarify the seed germination
      percentage of these four Rhododendron species using different photoperiods (0, 1,
      4 and 16 h). All statistical analyses were performed using Statistical Package
      for the Social Science (SPSS12.0) for Windows software program. The data were
      analyzed using Tukey's multiple range test at the p<0.05 significance level.
      RESULTS: After 30 days, no seed germination occurred in darkness. The highest
      average seed germination percentages were all observed at 700 lux: R.
      breviperulatum (83.3%), R. kanehirai (68.9%), R. ovatum (85.6%) and R. simsii
      (92.2%). The highest average germination percentages of seeds were observed in R.
      breviperulatum at 16 h (83.3%), R. kanehirai at 1 h (60.0%), R. ovatum at 16 h
      (84.4%) and R. simsii at 16 h (85.6%). According to the results, these four
      Rhododendron species required light for germination. There were significant
      differences (p<0.05) in the seed germination of these four Rhododendron species
      for light intensity greater than 700 lux. Similar results were observed with
      photoperiods. CONCLUSION: The seed germination percentage of R. breviperulatum,
      R. ovatum and R. simsii increased with increasing photoperiod.

PMID- 29023038
TI  - Evaluation of Autothermal Thermophilic Aerobic Digester Performance for the
      Stabilization of Municipal Wastewater Sludge.
AB  - BACKGROUND AND OBJECTIVE: Sludge stabilization process in terms of operational,
      environmental and economic indexes is the most important stage of treatment and
      its disposal. This study was aimed to determine the performance of Autothermal
      Thermophilic Aerobic Digestion (ATAD) system as one of the low-cost and
      biocompatible methods of sludge treatment. MATERIALS AND METHODS: This study has
      been done using a laboratory scale Autothermal Thermophilic Aerobic Digestion
      (ATAD). The reactor was consisted of two polyethylene tanks with a final capacity
      of 100 L for each tank. Both tanks with all fittings were installed on a metal
      frame. The variables of study were temperature, dissolved oxygen, pH, volatile
      organic compounds, total solids, COD and the number of Ascaris eggs and fecal
      coliforms per gram of dry matter of the sludge. The temperature was measured
      hourly and the pH and dissolved oxygen were measured and controlled twice per
      day. One-way ANNOVA was applied to analyze reasults. RESULTS: According to the
      results, the temperature of sludge increased from 11.7-61.2 degrees C by
      biological reactions. Pathogen organisms were reduced from 80*106 to 503 in
      number during 72 h. After 6 days pathogen organisms and Ascaris eggs were removed
      completely. Volatile organic compounds and COD were reduced 42 and 38.3%
      respectively during the 6 days. CONCLUSION: It is concluded that the performance
      of ATAD in removing organic compounds from wastewater sludge were desirable.
      Resulted sludge from stabilization process were appropriate for use in
      agriculture as a soil supplement and met the indexes of class A sludge according
      to EPA's standards (CFR 40 Part 503).

PMID- 29023039
TI  - Molecular Epidemiology of High-Risk Human Papillomavirus in High-Grade Cervical
      Intraepithelial Neoplasia and in Cervical Cancer in Parakou, Republic of Benin.
AB  - Human papilloma virus (HPV) infection remains a worldwide concern, especially in
      Sub-Saharan Africa where cervical cancer is the leading cause of cancer death in
      women. The aim of the study was to determine the prevalence and genotypic
      distribution of High-Risk HPV (HR-HPV) involved in Cervical Intraepithelial
      Neoplasia (CIN) II and III and in cervical cancer in Parakou. Out of a total of
      149 samples of cervical tissues archived, fixed and paraffin-embedded, 78 samples
      with histological diagnosis of CIN-II, CIN-III and cervical cancer went through
      deparaffinization with xylene, followed by an extraction of HPV DNA and the
      detection of HR-HPV by real-time multiplex PCR. The average age of the women was
      40.05+/-13.99 years. The samples were positive to at least one HR-HPV genotype in
      76.92% (50/65) of cases. The HR-HPV genotypes which are most common in the
      cervical cancer and in CIN-II and III were, respectively HPV-39 (38 and 37.50%),
      HPV-18 (35 and 31.30%), HPV-45 (35 and 31.30%), HPV-35 (9 and 25%) and HPV-52 (9
      and 12.50%). The HPV-16 was absent. This study helped to detect (in samples
      archived, fixed and paraffin-embedded tissues) HR-HPV involved in high-grade
      precancerous lesions and in cervical cancer in Parakou, some of which are not
      covered by currently available vaccines.

PMID- 29023040
TI  - Effects of Feeding Rates on Growth Performance, Feed Utilization and Body
      Composition of Asian Red Tail Catfish (Hemibagrus wyckioides), Cultured in
      Northeast Thailand.
AB  - Two experiments were carried out at the Khon Kaen University, Nong Khai Campus,
      Thailand during November, 2011 to May, 2012 to search for the most appropriate
      rates of feeding rations for fingerling and juvenile Asian redtail catfish
      (Hemibagrus wyckioides). A Completely Randomized Design (CRD) with three
      replications was used for both experiments. Experiment 1 had four treatments,
      i.e., T1 (2%), T2 (3%), T3 (4%, control), and T4 (5%). The same experimental
      design was used for the experiment 2, where four treatments were used, i.e., T1
      (1%), T2 (2%), T3 (3%, control) and T4 (4%). The percentages of the amounts of
      rations used for Experiments 1 and 2 were based on body-live weight per day.
      Fingerling and juvenile fish were used for the experiments 1 and 2, respectively.
      Each experiment was carried out for 10 weeks. The results showed that a rate of
      5% body live weight per day for fingerling fish of T4 of experiment 1 is the most
      appropriate rate for the fingerling fish. An increase in ration rate highly
      increased final body live weight. For juvenile fish of the experiment 2, it was
      found that there were no significant differences in live weights amongst the
      treated fish yet weight gained and specific growth rates between T1 and the rest
      were highly significant, whereas the results of the juvenile fish of T2 up to T4
      were similar hence, 2% body live weight per day of T2 is the most appropriate
      rate for juvenile fish.

PMID- 29023041
TI  - DNA Barcoding Uncover Cryptic Diversity in Goat Fishes (Family: Mullidae) Across
      the Egyptian Coastal Waters.
AB  - Despite ongoing efforts to protect species and ecosystems in the egyptian costs
      of the Red Sea and Mediterranean Sea, habitat degradation, overfishing and
      pollution have posed serious challenges to marine natural resources. In spite of
      the accumulated knowledge on the systematics of commercial fishes in Egypt recent
      results suggested that we are far from having a complete picture of egyptian fish
      diversity. The accurate identification of species is a very important component
      in many fields of biological research and conservation efforts. The high level of
      expertise and time consuming process needed means a loss in biodiversity.
      Successful species identification is now frequently based on a combination of
      approaches including morphometrics and the sequencing of the mitochondrial COI
      gene known as the DNA barcoding. This study employed COI sequencing alongside
      traditional taxonomic identification methods and uncovered cryptic diversity
      within the goat fish species of Family Mullidae, four species collected from both
      the Red Sea and the Mediterranean Sea. Upeneus pori, Upeneus vittatus, Mullus
      surmuletus and Mullus barbatus samples from the Red Sea and the Mediterranean
      were clustered separately in a NJ tree indicating the possibility of the presence
      of cryptic species complex. All species could be differentiated by their COI
      sequence.

PMID- 29023042
TI  - Alteration Expression of Bax, Bcl-2 and VDAC1 Genes in Oligozoospermic and
      Fertile Subjects.
AB  - One of factors causing oligozoospermic circumstances is excessive apoptosis
      during spermatogenesis. Spermatogenesis known involves Bcl-2 family proteins in
      cytoplasm and Voltage Dependent Anion Channel 1 (VDAC1) in outer mitochondrial
      membrane to facilitate releasing of apoptosis factor such as cytochrome-c from
      inter-membrane space into cytoplasm. The study was aimed to analyze the mRNA
      expression of pro-apoptotic Bax, anti-apoptotic Bcl-2 and VDAC1 genes derived
      from 45 oligozoospermic subjects and 20 fertile subjects as control. Analysis of
      transcript expression was performed by two-steps real-time (PCR) and calculating
      by standard curve method. Stages of works were followed: Analysis of sperm basal
      characterization, isolation of spermatozoa to separate it from cement and
      resulted pellets. Pellets were saturated with PBS to obtain mRNA and reversed
      into cDNA. The cDNA were sequenced to investigate SNP of Bax, Bcl-2 and VDAC1
      genes. Results showed that comparison of log mRNA copy number of Bax, Bcl-2 and
      VDAC1 genes for oligospemic and fertile subjects varied. The Bax, Bcl-2 and VDAC1
      were significantly different between oligozoospermic and normozoospermic subjects
      (p = 0.000, p = 0.041, p = 0.000, respectively). It was suggested that
      oligozoospermia may be occurred by inducing the increase of Bax pro-apoptotic and
      VDAC1 genes expression and decreasing of Bcl-2 expression to lead the excessive
      of apoptosis.

PMID- 29023043
TI  - Characterization of alpha-Amylase from Soursop (Annona muricata Linn.) Fruits
      Degraded by Rhizopus stolonifer.
AB  - Rhizopus stolonifer is a fungus and one of the most common species of the genus
      Rhizopus. The organism has been a very important microbe used in the field of
      industrial microbiology. It has been used in the production of many hydrolytic
      and extracellular enzymes among which is the alpha-amylase. This enzyme has found
      various uses in the industry. Fruit juices are important sources of nutrients and
      they contain several important therapeutic properties that may reduce the risk of
      various diseases. An investigation on alpha-amylase extracted from soursop fruits
      deteriorated by R. stolonifer and the effect of the enzyme on soursop juice
      clarification was carried out in this study. The results obtained shows that the
      soursop juice with low concentration of extracted enzyme and less incubation time
      was more viscous and cloudy compared with the juice with high concentrations of
      amylase and higher incubation time which was clearer and less viscous. The
      results of this research will be very useful in soursop juice producing
      companies.

PMID- 29023044
TI  - Competitive and Allelopathic Effects of Wild Rice Accessions (Oryza
      longistaminata) at Different Growth Stages.
AB  - The competitive and allelopathic effects of wild rice (Oryza longistaminata)
      accessions on barnyard grass at different growth stages determined by days after
      sowing (0, 30, 60 and 90 days) were studied in greenhouse pot experiments. Wild
      rice accession RL159 exhibited the greatest height and tillering. The weed
      suppression rates of wild rice accessions OL and F1 on barnyard grass were
      significantly higher than for other rice accessions, with the lowest being O.
      sativa cultivar RD23. The highest suppression rates of OL and F1 were 80.23 and
      73.96% at barnyard grass growth stages of 90 days and 60 days. At a 90 growth
      stage, wild rice accessions RL159 and RL169 caused 61.33 and 54.51% inhibition in
      barnyard grass growth, respectively. Under the same conditions, the competitive
      inhibition rates of OL, F1, RL159, RL169 and RL219 against barnyard grass were
      markedly lower than their weed suppressive effects, but were relatively similar
      for RD23. The allelopathic inhibition of OL and F1 on barnyard grass was
      significantly higher than other rice accessions. The highest allelopathic rates
      of OL and F1 were 60.61 and 56.87% at the 0 day growth stage. It is concluded
      that wild rice accessions OL and F1 exhibited the highest allelopathic activity
      along with moderate competitive ability against barnyard grass; wild rice
      accession RL159 had the highest competitive ability and moderate allelopathic
      activity on barnyard grass. Thus, the three wild rice accessions OL, F1 and RL159
      could be used as ideal breeding materials for cultivated rice improvement.

PMID- 29023045
TI  - Acute Toxicity of Cashew Nut Shell Extract (Anacardium occidentale L.) In Albino
      Rat (Rattus norvegicus Berkenhout 1769).
AB  - Cashew plant (Anacardium occidentale L.) is a crop producing cashew nut shell
      that contain phenolic compounds such as lacquer oil (cashew nut shell liquid)
      which can be used for many studies. This study was conducted to determine the
      potency of acute toxicity (LD50) of cashew nut shell extract on female albino
      Wistar rats using Weil method. Twenty rats used in this study. The rats was
      divided into five groups, each consist of four rats after acclimatization. Each
      group was given the extract of cashew nut shell orally (force-fed). The amount of
      cashew nut shell extract that were given to group I, II, III and IV were 2.5, 25,
      250 and 2,500 mg kg-1 b.wt., respectively, while group V were given 0.5% sodium
      carboxyl methyl cellulose (CMCNa) solution. Clinical symptoms were observed 24 h
      after the administration of extract include behavioral changes i.e., licking,
      scratching, twitching, tremors, wrihing, reactivity to stimuli, cerebral and
      spinal reflexes, secretions, breath, skin, hair and death. Probit analysis using
      Weil method was used as an effective dose. The results showed that the potency
      for acute toxicity (LD50) of cashew nut shell extract was 2,018 mg kg-1 which
      classified as moderately toxic category. The administration of extract also
      causes behavioral changes in animal including passivity and mucus secretion. All
      doses of the extract did not affect the development body weight and the weight of
      organs (spleen, liver, heart, kidneys and lungs) in female rats.

PMID- 29023046
TI  - Assessment of Pesticide Residues in Human Blood and Effects of Occupational
      Exposure on Hematological and Hormonal Qualities.
AB  - Pesticides are the first choice by farmers for use against plant pathogens,
      nevertheless their adverse effects to the environment. Current study was designed
      to measure pesticides residues in blood of spray farmers and to assess their
      possible effects. Blood indices and thyroid and reproductive hormones were
      evaluated in blood of adult male volunteers (20-48 years old). Volunteers were
      divided to three groups; spray-workers (directly-exposed), farmers who live in
      the country area (indirectly-exposed) and city inhabitants (not exposed). Spray
      workers had significantly decreased platelet number (PLT, 33%), ratio of large
      platelet (P-LCR%, 42%), average platelet volume (MPV, 70%), relative width of the
      distribution of erythrocytes (PDW, 56%), relative content of monocytes, basophils
      and eosinophils (MXD, 100%) compared to control group. In addition, blood samples
      of the exposed group showed significantly decreased PLT (30%), P-LCR (40%), MPV
      (65%) and PDW (50%) compared to the farmers. Furthermore, levels of testosterone,
      triiodothyronine and thyroxine hormones of spray workers were significantly low
      compared with the country residents. Then results were further subjected to
      canonical discriminant analysis to visualize the interrelationships among
      variables. Results highlighted the critical need for enforced official
      interventions that reduce overexposure of spray workers throughout Egypt.

PMID- 29023047
TI  - Recombinant Engineering of L-Methioninase Using Two Different Promoter and
      Expression Systems and in vitro Analysis of Its Anticancer Efficacy on Different
      Human Cancer Cell Lines.
AB  - Recombinant methioninase (rMETase) is an enzyme that has antitumor activity. In
      this work, METase gene from Pseudomonas putida ATTCC 8209 was cloned to pT7-7
      plasmid (yielded, PT7-METase-R7 clone) and expressed in E. coli strain BL21
      (DE3). A protein band with a molecular massof 42 kDa was visualized by SDS-PAGE.
      The applied protocol yielded a total protein of 3.13 g with a recovery of 66.89%
      and a specific activity of 18.59 U mg-1 which considered as a low yield. However,
      when the METase gene was cloned to the vector (pTrc99A, clone: pTrc99A-MET-3)
      cells of E. coli JM109 yielded a total protein of 32.63 g with a recovery of
      41.62% and a specific activity of 54.86 U mg-1 which revealed that the
      enhancement of METase gene expression by trc promoter was more than the T7 RNA
      polymerase promoter. The t1/2 of the rMETase was 2 h asanalyzed in mice by IV
      injection. Antitumor efficacy of rMETase was studied in five human cancer cell
      lines. At 1 U mL-1 the growth rate of treated colon cancer cell lines, Colo205
      and SW620, with rMETase was 46 and 32% relative to control, respectively. With
      the ovarian cancer cell line (A2780) rMETase produced an inhibition effect of 54%
      at 1.5 U mL-1. In addition, the growth rate was reduced to 45 and 53% with the
      skin cancer cell line (A375) and the breast cancer cell line (MCF-7),
      respectively. These results indicate the feasibility of rMETase for use as a
      potent antitumor agent.

PMID- 29023048
TI  - Level of Heavy Metals in Two Highly Consumed Fish Species at District Lower Dir,
      Khyber Pakhtunkhwa, Pakistan.
AB  - The current study was designed to assess heavy metals' concentration in muscle
      tissues of two Chinese carps, common carp (Cyprinus carpio) and silver carp
      (Hypophthalmichthys molitrix), available to consumers in markets at district
      Lower Dir, Khyber Pakhtunkhwa, Pakistan. Fish specimens were collected from three
      main markets in the study area namely; Chakdara, Timergara and Khall. Heavy
      metals including; manganese (Mn), lead (Pb), iron (Fe), copper (Cu), zinc (Zn),
      cadmium (Cd) and cobalt (Co) were investigated using atomic absorption
      spectrophotometer. Cobalt was not detected in any of the fish specimens while the
      rest of the metals were lying within the permissible limits suggested by FAO/WHO
      and ITS for food/fish consumption. The results showed a statistically significant
      (p<0.05) difference between both species with respect to the concentration of the
      accumulated heavy metals. In common carp, the heavy metal accumulation was in
      order of Fe>Mn>Zn>Pb>Cu>Cd, while in silver carp the order was Fe>Mn>Zn>Pb>Cd>Cu.
      Higher concentration of Pb, Mn, Zn, Cu and Cd was recorded in muscle of common
      carp while the concentration of Fe was higher in silver carp, indicating higher
      potential of accumulation of heavy metals in common carp. Statistically
      significant (p<0.05) correlation was observed between Pb and Zn in common carp
      while between Cu and Cd in silver carp. The concentration of heavy metals was in
      the suggested permissible limits and poses no threat if consumed. In order to
      maintain the heavy metals level within permissible limits, proper care should be
      taken along with regular assessment.

PMID- 29023049
TI  - Study of Genetic Marker of Cuscuses (Marsupialia: Phalangeridae) from Maluku and
      Papua Based on Cytochrome b Gene Sequences.
AB  - Cuscuses is marsupials animal (Phalangeridae) which has limited spread in eastern
      Indonesia (Sulawesi, Maluku, Papua and Timor islands), Australia and Papua New
      Guinea. The ex-situ and in-situ conservation of cuscuses under captivating
      condition is an alternative solution to protect from extinction. This study aimed
      to determine nucleotide sequences and genetic marker on cyt b gene with
      sequencing method of each species on two provinces. Whole genome DNA was
      extracted from 22 samples of cuscuses obtained from different habitats, Maluku
      (13 individuals) and Papua (8 individuals) according to the protocol of Qiamp DNA
      Blood Mini Kit (Qiagen) and then it was used as template for amplification of cyt
      b gene by using PCR method. The PCR product were then purified using column
      chromatography and were used as template for sequencing reaction. Results
      sequencing of cyt b gene were analyzed using MEGA program versions 6.0. The PCR
      product gives results nucleotides of 982 bp according to database GeneBank and
      sequencing product gives results nucleotides of 771 bp. Nucleotides alignment of
      Phalanger members was found 24 nucleotides distinguishing and Spilocuscus members
      was found 11 nucleotides distinguishing, which can be used as genetic marker
      between Phalanger and Spilocuscus members from Papua and Maluku.

PMID- 29023050
TI  - Molecular Diagnosis of Clinical Isolates of Cutaneous Leishmaniasis Using ITS1
      and KDNA Genes and Genetic Polymorphism of Leishmania in Kashan, Iran.
AB  - Cutaneous leishmaniasis is a common skin disease caused by leishmania parasite.
      An accurate diagnosis of parasites species is possible using molecular
      techniques. This study was carried out to compare internal transcribed spacer
      (ITS1) and kinetoplast deoxyribonucleic acid (KDNA) genes for identifying
      Leishmania species by Polymerase Chain Reaction (PCR), furthermore, genetic
      diversity of isolates was studied. This research examined 130 patients who were
      suspected of cutaneous leishmaniasis and referred to Kashan's health centers from
      2011-2014. After DNA extraction from serosity, PCR were performed using ITS1 and
      KDNA primers. Cutaneous Leishmaniasis was diagnosed by the observation of 320 bp
      band in the ITS1-PCR. The PCR products were digested with restriction enzyme
      HaeIII and then leishmania species were identified by patterns of enzymatic
      digestion. The diagnostic criteria of Cutaneous Leishmaniasis (CL) in KDNA-PCR
      were based on the observation of 760 and 650 bp for Leishmaniasis tropica and
      Leishmaniasis major, respectively. Twelve isolates of leishmania were sequenced
      and the phylogenetic tree was traced using the results of sequencing by Mega 4
      software. Out of 130 suspected patients to CL, 70 (53.8%) and 98 (75.4%) isolates
      were positive by Restriction Fragment Length Polymorphism (RFLP) of ITS1 and
      KDNA, respectively. Using ITS1 PCR, 60 samples (85.7%) and 10 samples (14.3%)
      were identified as L. tropica and L. major, respectively, ITS1-PCR had 25.3%
      false negative, compare to microscopy. While, microscopy had false negative in 13
      cases compare to KDNA-PCR. Due to the lower sensitivity of the PCR-RFLP of ITS1,
      KDNA-PCR is recommended for diagnosis of CL. The L. tropica and L. major are the
      causative agents of CL.

PMID- 29023051
TI  - Nutritional Properties Assessment of Endogenous and Improved Varieties of Maize
      (Zea mays L.) Grown in Southern Benin.
AB  - BACKGROUND AND OBJECTIVE: A wide range of maize varieties is used in Benin but
      information on the nutritional characteristics of these varieties are not well
      known. This study aims to assess the nutritional composition of maize varieties
      in use in the southern region of Benin with the purpose of providing consumers
      accurate information for better choice. MATERIALS AND METHODS: Moisture, ash,
      protein, fiber and fat contents were determined according to Association of
      Official Analytical Chemists and American Association of Cereal Chemists methods.
      Sugar and organic acids were assessed using High Performance Liquid
      Chromatography methods and amino acids profile was established according to Rosen
      method using glutamic acid. RESULTS: The maize varieties were classified into 5
      clusters according to their macro nutrients composition and 4 clusters based on
      their sugar and organic acids contents. Varieties of group 5 were very rich in
      protein (14.34 g/100 g), while the highest fat content (7.22 g/100 g) was
      observed for group 2 varieties. The highest carbohydrate contents obtained were
      80.64 g/100 g, 80.11 g/100 g and 79.15 g/100 g for groups 1, 4 and 5 varieties
      respectively. Moreover the dendrogram gave four homogeneous clusters according to
      sugars and organic acids composition. Varieties of groups 2, 3 and 4 had almost
      the same fructose contents ranging between 0.04 and 0.06%; varieties of group 1
      contained the highest contents of raffinose, sucrose and glucose; those of group
      2 were very rich in propionate and fructose. CONCLUSION: It is concluded that
      some of maize varieties investigated contained high level of protein. Furthermore
      glutamic acid was the predominant amino acid while the least amino acid was
      methionine. Those varieties, owing to their protein and amino acids contents
      could have many benefits by providing vital constituents to the body.

PMID- 29023052
TI  - Effect of Salicylic Acid on the Growth and Chemical Responses of Pectobacterium
      carotovorum subsp. carotovorum.
AB  - BACKGROUND AND OBJECTIVE: Salicylic acid is a signal molecule which activates
      plant defense against plant pathogens such as the soft rot enterobacterium
      Pectobacterium carotovorum subsp. carotovorum. The objectives of study were to
      determine bactericidal effects of salicylic acid on the growth of P. carotovorum
      subsp. carotovorum and secondly, assess chemical responses of P. carotovorum
      subsp. carotovorum to salicylic acid. MATERIALS AND METHODS: Pectobacterium
      carotovorum subsp. carotovorum was grown in lysogeny broth amended with salicylic
      acid at concentrations of 0, 100, 200, 400, 800 and 1200 mg L-1. The P.
      carotovorum subsp. carotovorum cultures were incubated at 25 degrees C and
      sampled at two time points, 0 h (sampled before incubation) and 24 h. Bacterial
      counts were done at the onset of the incubation (0 h) and after the 24 h
      incubation. The set which was incubated for 24 h was split into two, one subset
      was centrifuged and the other was not. From the centrifuged subset the
      supernatant was recovered and was, together with all the other samples (0 and 24
      h not centrifuged), analyzed with1H nuclear magnetic resonance and gas
      chromatography. RESULTS: Bacterial counts done before and after incubation showed
      that the lower concentrations of salicylic acid, 0, 100, 200 and 400 mg L-1,
      supported the growth of P. carotovorum subsp. carotovorum whereas the higher
      concentrations of 800 and 1200 mg L-1 inhibited the growth of the bacterium
      completely. Nuclear magnetic resonance results showed either slight or no
      differences in the metabolite profiles and gas chromatography showed different
      responses without a clearly defined pattern among the experimental treatments.
      However, methanethiol was detected by both nuclear magnetic resonance and gas
      chromatography in all the treatments and was probably formed as a result of the
      breakdown of lysogeny broth. CONCLUSION: From the results obtained it was
      concluded that salicylic acid promotes the growth of P. carotovorum subsp.
      carotovorum at lower concentrations of 0-400 mg L-1 but higher concentrations of
      salicylic acid of 800 and 1200 mg L-1 inhibit bacterial growth. All the tested
      salicylic acid concentrations (0-1200 mg L-1) cause only slight chemical shifts
      in the bacterial culture. Methanethiol was detected in all treatments and it is
      probably formed from the breakdown of lysogeny broth.

PMID- 29023053
TI  - Effect of Antioxidants on Testicular iNOS and eNOS after High-Fat Diet in Rat.
AB  - BACKGROUND AND OBJECTIVE: Spermatogenesis is a process by which germ cells
      produce spermatozoa and can be disturbed at every level. Nitric Oxide Synthases
      (NOS), implicate in interactions with Oxidative Stress (OS) which is one of the
      main factors in the etiology of male infertility. The High Fat Diet (HFD) is a
      major factor of obesity which in turn is important for enhancing OS. Antioxidants
      and garlic could attenuate or reverse effects of HFD. The aim of the study was to
      investigate the effects of dietary antioxidants and garlic on testicular
      inducible NOS (iNOS) and endothelial NOS (eNOS) in Wistar albino rats fed on HFD.
      MATERIALS AND METHODS: Groups (each n = 8) were: SD (100% access to standard
      diet), F-HFD, (100% access to HFD) and R-HFD (70% access to HFD), F-HFD
      +antioxidants, F-HFD+garlic and R-HFD+antioxidants. The HFD consisted of a 60%
      fatty diet in 3 forms: Without antioxidants, with antioxidants and with garlic.
      The testicular iNOS and eNOS were studied by immunohistochemical (IHC) method.
      Also used ANOVA, repeated measures ANOVA, t-tests and Tukey's test (where
      necessary) to analyze the data (p<0.05). RESULTS: The iNOS increased in the F-HFD
      and R-HFD+antioxidants groups. The eNOS increased in R-HFD,F-HFD and F-HFD+garlic
      groups. The H-E evaluation in R-HFD group showed a decrease in spermatogenesis
      score count and seminiferous tubules diameters (MUm) in comparison with the SD
      and F-HFD groups. R-HFD+antioxidants group had lower score than F
      HFD+antioxidants and F-HFD+garlic groups. CONCLUSION: Restricted fat diet
      consumption causes increase in weight and impairs spermatogenesis. Results of
      this study reveal that adding the antioxidants can't improve histological changes
      of testis. The iNOS expression in seminiferous tubules in restricted fat diet
      along with antioxidants, suggest a potential role of iNOS in spermatogenesis and
      male infertility.

PMID- 29023054
TI  - Genetic Characterization, Antimicrobial Resistance Patterns and Virulence
      Determinants of Staphylococcus aureus Isolated form Bovine Mastitis.
AB  - BACKGROUND AND OBJECTIVE: Staphylococcus aureus is commonly associated with
      mastitis in dairy herds with potential public health implications. This study was
      conducted to investigate the existence of S. aureus in mastitic milk and to
      determine the antimicrobial resistance profiles of the isolated strains as well
      as the resistance and virulence associated genes. MATERIALS AND METHODS: Two
      hundred quarter milk samples were collected from 3 dairy farms at Dakahliya (n =
      2) and Damietta (n = 1) Governorates, Egypt from September to December 2016.
      Conventional culturing and Polymerase Chain Reaction (PCR) assays targeting nuc
      (thermonuclease) and coa (coagulase) genes were performed. Isolates were tested
      for its susceptibility against 14 antimicrobial agents using disk diffusion
      method. All the isolates were screened for the presence of beta-lactamases (blaZ,
      mecA) and virulence associated (pvl and tst) genes by PCR. RESULTS: The S. aureus
      was detected in 42% (84/200) of the total examined milk samples. Regarding the
      antibiogram results, S. aureus revealed a high resistance against ampicillin
      (95.2%) and penicillin (83.3%) and a lower resistance was observed against
      gentamicin (23.8%), amikacin (16.7%) and ciprofloxacin (14.3%). Multidrug
      resistances were detected in 83.3% of the isolated S. aureus. Of the 70
      penicillin-resistant S. aureus isolates, blaZ gene was identified in 67 (95.7%)
      isolates. Fifty percent of S. aureus isolates harbored the specific amplicon of
      mecA gene. Markedly, all mecA positive strains displayed multidrug resistance and
      were also positive for blaZ gene. The virulence determinants pvl and tst were
      detected in 7.1 and 11.9% of the isolated S. aureus, respectively. CONCLUSION:
      Presence of multidrug resistant and toxin producing S. aureus in dairy farms pose
      a major risk to public health. Therefore, this study highlighted the importance
      of developing an efficient control program to inhibit the transmission of S.
      aureus, particularly multidrug resistant strains to humans.

PMID- 29023055
TI  - Isolation of Potential Bacteria as Inoculum for Biofloc Formation in Pacific
      Whiteleg Shrimp, Litopenaeus vannamei Culture Ponds.
AB  - BACKGROUND AND OBJECTIVE: A new green technology to reduce environmental damages
      while optimizing production of Pacific Whiteleg shrimp, Litopenaeus vannamei was
      developed known as "Biofloc technology". Microbial communities in biofloc
      aggregates are responsible in eliminating water exchange and producing microbial
      proteins that can be used as supplemented feed for L. vannamei. This study aimed
      to isolate and identify potential bioflocculant-producing bacteria to be used as
      inoculum for rapid formation of biofloc. MATERIALS AND METHODS: For the purpose
      of this study, bacterial communities during 0, 30 and 70 days of culture (DOC) of
      L. vannamei grow-out ponds were isolated and identified through phenotypic and
      16S rDNA sequences analysis. Phylogenetic relationships between isolated bacteria
      were then evaluated through phylogenetic tree analysis. One-way analysis of
      variance (ANOVA) was used to compare the differences of microbial communities at
      each DOC. RESULTS: Out of 125 bacterial isolates, nine species of bacteria from
      biofloc were identified successfully. Those bacteria species were identified as
      Halomonas venusta, H. aquamarina, Vibrio parahaemolyticus, Bacillus infantis, B.
      cereus, B. safensis, Providencia vermicola, Nitratireductor aquimarinus and
      Pseudoalteromonas sp., respectively. Through phylogenetic analysis, these
      isolates belong to Proteobacteria and Firmicutes families under the genera of
      Halomonas sp., Vibrio sp., Bacillus sp., Providencia sp., Nitratireductor sp. and
      Pseudoalteromonas sp. CONCLUSION: In this study, bioflocculant-producing bacteria
      were successfully identified which are perfect candidates in forming biofloc to
      reduce water pollution towards a sustainable aquaculture industry. Presence of
      Halomonas sp. and Bacillus sp. in all stages of biofloc formation reinforces the
      need for new development regarding the ability of these species to be used as
      inoculum in forming biofloc rapidly.

PMID- 29023056
TI  - Ameliorative Effect of Arctium lappa Against Cadmium Genotoxicity and
      Histopathology in Kidney of Wistar Rat.
AB  - BACKGROUND AND OBJECTIVE: Cadmium (Cd) is a non-essential metal whose dispersion
      in the environment has increased recently, Cd may enhance cell oxidative stress
      that leads to DNA damage and apoptotic cell death. The study aimed to evaluate
      the antioxidative capability of Burdock root 'Arctium lappa' on cadmium-induced
      oxidative stress and histopathology of the kidney of Wistar rats. METHODOLOGY:
      Cadmium was applied in a form of cadmium chloride to three groups (15 mg Cd kg-1)
      for five weeks with two groups pre-treated with 'Arctium lappa' administration,
      100 and 200 mg kg-1 b.wt. Data were analyzed using one way analysis of variance
      (ANOVA) followed by Least Significant Difference (LSD) test to determine the
      difference among means using the JMP version 12. RESULTS: Results revealed that
      cadmium induced a significant disorganization (p<0.05) of renal structure with
      collapsed tubular lamina and 76 MUm tail length of the cells was observed, while
      histological sections of kidney pre-treated with 100 mg Arctium lappa kg-1 b.wt.,
      showed a slightly less hypercellularity of glomerulus and reduction in the cell
      tail (59 MUm). Furthermore, histological sections of kidney of rats pre-treated
      with 200 mg Arctium lappa kg-1 b.wt., showed high improvement of renal tubules
      and glomerulus with a prominent urinary space beside tail length of cells was
      recorded as 39 MUm which was lower in comparison to other groups. CONCLUSION:
      Moreover, cadmium induced cellular destruction of the kidney was resumed with the
      pre-treatment of the secondary metabolites as an antioxidant compounds that
      produced from plant extracts. Arctium lappa leaf extract was efficient at both
      applied doses while 200 mg Arctium lappa kg-1 b.wt., had the most ameliorative
      effect.

PMID- 29023057
TI  - Dynamic of Bacterial Diversity in Ileum Digesta Under Water Supplements of
      Antibiotics and Probiotics.
AB  - BACKGROUND AND OBJECTIVE: Intestinal bacteria plays an important role in the
      physiological and immunological status of birds. The present study investigated
      the diversity of intestinal bacterial of broilers that were fed corn-soy diet and
      supplements of antibiotics and probiotics. MATERIALS AND METHODS: The
      supplemented treatments were water, water with antibiotics, water with probiotic
      and water with antibiotics and probiotic. Eight randomly sampled broilers were
      slaughtered and their ileum digesta taken. The total of 32 samples was then
      subjected for DNA extraction. Subsequently, bacterial tag-encoded 16 FLX
      ampliconpyro sequencing (bTEFAP) procedures were performed. RESULTS: Nearly all
      treatments samples contained Lactobacillus, with the majority related to water
      with probiotic treatment. In contrast, different pathogenic bacteria along with
      Lactobacillus observed for other three treatments. CONCLUSION: The probiotics
      supplements made a shift towards useful bacterial species; Lactobacillus
      salivarius and Lactobacillus aviarius. This study promoted for replacing the
      probiotics as a prophylaxis in gastrointestinal infection and diseases instead of
      antibiotics.

PMID- 29023058
TI  - Morphometric Characteristics of Asian Catfish, Hemibagrus wyckii (Bleeker, 1858)
      (Bagridae), from the Riau Province of Indonesia.
AB  - BACKGROUND AND OBJECTIVE: Asian Catfish (Hemibagrus wyckii) is an important fish
      having both food and a high price in the market. These species are categorized as
      a carnivorous freshwater finfish native in Indonesia and is vulnerable to
      endangered status. This study was carried out to identify the morphometric
      characteristics of Hemibagrus wyckii (H. wyckii) from the Koto Panjang Reservoir,
      Kampar Kanan and Kampar Kiri rivers. MATERIALS AND METHODS: Twenty-five fish were
      collected from each sampling site. The morphometric characteristics were analyzed
      using the truss morphometric method. Twenty-nine characteristics were measured to
      obtain the morphometric characteristics of this species. Morphometric data of H.
      wyckii were analyzed using one-way ANOVA (SPSS version 17.0). Principal component
      analysis (PCA) was used to evaluate the relationship between different factors
      and morphometric characteristics. The distribution across different habitats was
      measured by component canonical analysis (CCA) and genetic distance was analyzed
      by hierarchical cluster. RESULTS: The average standard lengths of H. wyckii from
      the Koto Panjang Reservoir, Kampar Kanan and Kampar Kiri rivers (Mean+/-SD) were
      428+/-15.78, 432.52+/-66.11 and 425.86+/-50.41 mm, respectively. Twenty-nine
      morphometric characteristics were measured. There was a 68.96% difference
      obtained in samples collected at the Koto Panjang Reservoir and Kampar Kanan
      river. There was a 95.55% difference obtained in the Koto Panjang Reservoir,
      Kampar Kiri river and a 100% difference obtained in the Kampar Kanan and Kampar
      Kiri rivers. The main differences in morphometric characteristics included inter
      orbital distance, length of adipose-fin base, predorsal length, length of front
      dorsal fin-front pelvic and depth of caudal peduncle. The Mahalanobis distance
      between fish from the Koto Panjang Reservoir and Kampar Kanan river demonstrated
      that both types originated from a single population. CONCLUSION: It was concluded
      that more favorable morphometric characteristics of H. wyckii were found in the
      Kampar Kanan river compared to those from the Koto Panjang Reservoir and Kampar
      Kiri river.

PMID- 29023059
TI  - Hematological and Mineral Profiles of Reproductive Failure of Exotic Breed Cattle
      in Payakumbuh, West Sumatra, Indonesia.
AB  - BACKGROUND AND OBJECTIVE: Female exotic breed cattle raised by traditional small
      farms are susceptible to reproductive disturbances that result in failure or
      delay to produce calves. The present research investigated the hematologic
      profiles of exotic breed cattle having reproductive troubles versus heifers and
      pregnant cows raised by small farms. MATERIALS AND METHODS: A survey was
      conducted to identify the reproduction performance of 160 female Simmental cows
      raised at 15 smallholders in Payakumbuh, West Sumatra, Indonesia. Samples of
      blood were collected from 15 female Simmentals comprised of three different
      reproductive statues (heifers, pregnant and reproductive failure, n = 5 animals
      each). Blood plasma was then separated and analyzed for hematological parameters
      [hemoglobin (Hb), hematocrit, red and white blood cell, mean corpuscular Hb
      concentration], total protein and mineral content (Ca, P, Mg, Fe, Mn, Cu and Zn).
      Samples of fodder feed were collected from 15 farms for determination of dominant
      species and mineral composition. Data were statistically analyzed in a completely
      randomized 3*5 design for blood parameters and 4*3 design for forage minerals.
      RESULTS: About one-third of female cows found to have reproductive problems.
      Anestrus was found to be the most important causal factor for reproductive
      failure, followed by postpartum infertility (poor fertilization). The
      reproductive failure group had significantly lower (p<0.05) Hb levels,
      hematocrit, red and white blood cell and protein but higher mean corpuscular Hb
      concentration. Considering the critical levels in the blood and feed, the animals
      were deficient in protein, Ca, P, Mn and Cu. CONCLUSION: Anestrus and repeated
      insemination were found to be the major causes of reproductive disorders in
      exotic breed cattle under small farm conditions that results in delay or failure
      to produce calves. Reproductive disturbances in Simmental cows were most likely
      associated with nutrient deficiencies.

PMID- 29023060
TI  - Polymorphism of Glutamate-Cysteine Ligase Subunit Catalytic (GCLC) Gene in
      Pulmonary Tuberculosis Patients.
AB  - BACKGROUND AND OBJECTIVE: The biomarker of oxidative stress in pulmonary
      tuberculosis patients has not been found. Oxidative stress occurs due to the low
      level of antioxidants. Single nucleotide polymorphism of glutamate-cysteine
      ligase subunit catalytic (GCLC) gene namely -129C/T GCLC has been reported to
      have an association with a risk factor of oxidative stress' susceptibility. The
      Objective of this study was to determine the GCLC polymorphism in pulmonary
      tuberculosis (TB) patient. MATERIALS AND METHODS: Blood samples of 225 pulmonary
      TB patients were taken from the central public health in Semarang city. The
      genetic test was carried out using polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP). The isolation of DNA from 225 blood samples was
      performed using DNA extraction kit (Promega DNA purification kit) following the
      manufacturing procedure. The amplification of GCLC fragment was performed by a
      master mix from Thermo Scientific. Data was analyzed descriptively. Statistical
      analysis was performed by Chi-square test. RESULTS: The results showed the
      existence of polymorphism-129C/T in the 5'-flanking region of GCLC genes. The
      frequency of C/C and C/T genotype were 63.6 and 36.4%, respectively. The C/T gene
      in the GCLC -129C region is a T gene promoter. There was a significant different
      between C/C and C/T frequencies with the value of significance of p = 0.000
      (p<0.05). CONCLUSION: Therefore it was concluded that the frequency of C/T
      polymorphism genotype of GCLC gene in patients with pulmonary tuberculosis is
      36.4%.

PMID- 29023061
TI  - Protective Role of Achillea biebersteinii Pretreatment on Dimethoate Induced
      Oxidative Stress in Guinea Pigs Liver.
AB  - OBJECTIVE: The present study investigated the influence of Achillea biebersteinii
      (Ab), a medicinal herb used widely in Yemeni's folk medicine as analgesic,
      antipyretic, against diarrhea and flatulence and for liver diseases, on the liver
      antioxidant potential of guinea pigs acutely intoxicated with dimethoate
      pesticide (DM). MATERIALS AND METHODS: Animals were administered with Ab aqueous
      extract (50 and 100 mg kg-1 b.wt., orally) or silymarin (100 mg kg-1 b.wt.,
      orally) for 2 weeks followed by single acute DM administration (80 mg kg-1 b.wt.,
      1/4 of the LD50 orally). Data were analyzed by one-way ANOVA using SPSS. RESULTS:
      The results showed that the treatment with Ab extract significantly lowered the
      DM induced serum levels of hepatic marker enzymes (AST, ALT and ALP). Liver
      histopathology also showed that Ab extract reduced the incidence of lesions
      including the swelling of cells, lymphocytes infiltration, nucleus fragmentation
      and condensation and necrosis induced by DM treatment in guinea pigs. CONCLUSION:
      The results of this study suggest that Ab aqueous extract could protect the liver
      against DM-induced oxidative damage.

PMID- 29023062
TI  - Biodegradation of Quinalphos by a Soil Bacterium-Bacillus subtilis.
AB  - BACKGROUND AND OBJECTIVE: A widely used pesticide quinalphos (O, O-diethyl O
      quinoxalin-2-yl phosphorothioate) may be an undesirable and persistent pollutant
      to non-target environments like rivers and other ecosystems. The objective of
      this study was to isolate a potential degradant bacterium of quinalphos from
      polluted soils and test its fitness under various culture conditions. MATERIALS
      AND METHODS: A soil bacterium strain, capable of utilizing quinalphos as its sole
      source of carbon and energy was isolated from soil by enrichment method on a
      minimal salts medium (MSM). On the basis of morphological, biochemical and 16S
      rRNA gene sequence analysis the bacterium is a species of the genus Bacillus and
      it was closely related to Bacillus subtilis. Quinalphos degrading capabilities of
      this bacterium were assessed under different culture conditions. Quinalphos
      degradation data were analysed byusing a two-way ANOVA analysis with the
      Statistica v.10. RESULTS: Bacillus subtilis grew on quinalphos with a generation
      time of 32.34 min or 0.54 h in the logarithmic phase. Maximum degradation of
      quinalphos was observed with an inoculum of 1.0 optical density, around pH-7.5
      and at an optimum temperature of 35-37 degrees C. Among the additional carbon and
      nitrogen sources, carbon source-glucose and nitrogen source-yeast extract
      marginally improved the rate of degradation of quinalphos. Gas chromatography
      mass spectrometry (GC-MS) analysis of the culture of B. subtilis grown on
      quinalphos indicated the formation of one main metabolite-quinoxaline.
      CONCLUSION: The B. subtilis strain discovered in this study has a unique
      combination of abilities to degrade quinalphos and it is therefore suitable
      candidate bioremediator of quinalphos polluted environments.

PMID- 29023063
TI  - Effectiveness of Metarhizium anisopliae and Entomopathogenic Nematodes to Control
      Oryctes rhinoceros Larvae in the Rainy Season.
AB  - BACKGROUND AND OBJECTIVE: Metarhizium anisopliae (MET) and entomopathogenic
      nematodes (EPN) are microorganisms that attack the larvae of Oryctes rhinoceros.
      The effects of MET, EPN and the combination of both on the O. rhinoceros larvae
      were studied during the rainy season in Jepara Indonesia. This study aimed to
      determine the effectiveness of Metarhizium anisopliae and entomopathogenic
      nematodes to control Oryctes rhinoceros larvae in the rainy season. MATERIALS AND
      METHODS: There were four level doses of MET, four level doses of EPN and four
      mixture of MET and EPN. The experiment used 72 containers that were placed in the
      garden with coconut palm shade. Five kilograms of organic soil that was mixed
      with biological control agents (MET, EPN and MET+EPN) and ten O. rhinoceros
      larvae 3rd instar were put in each other container. The data were analyzed by
      descriptive analysis. RESULTS: Every larvae mortality was observed once a week
      and observations are for 8 weeks. The result showed that the larval mortality due
      to MET treatment occurred on 2nd-7th week. Meanwhile, the larval mortality due to
      EPN treatment took place on 2nd-8th weeks and the larval mortality due to MET+EPN
      treatment occurred on 1st-5th weeks. CONCLUSION: The combination of MET and EPN
      was simultaneously effective to control O. rhinoceros larvae than separate use of
      MET or EPN. Result of this study showed that using two agents of biocontrol was
      more effective, so that it can be beneficial for controlling O. rhinoceros larvae
      in the field.

PMID- 29023064
TI  - Impact of Zeatin and Thidiazuron on Phenols and Flavonoids Accumulation in Callus
      Cultures of Gardenia (Gardenia jasminoides).
AB  - BACKGROUND AND OBJECTIVE: Gardenia (Gardenia jasminoides) has many
      pharmacological actions such as anti-inflammatory, antioxidant and fibrolytic
      activities and cytotoxic effects, etc. This study was conducted to recognize the
      effect of zeatin and thidiazuron (TDZ) on callus proliferation, total phenolic
      content, total flavonoids and DPPH scavenging activity of gardenia callus
      cultures. MATERIALS AND METHODS: Calli were cultured on Murashige and Skoog (MS)
      medium supplement with different concentrations (2, 4 or 6 mg L-1) of zeatin or
      TDZ individually as well as combination of 2 mg L-1 zeatin+4 mg L-1 TDZ. Cultures
      contained 4 mg L-1 TDZ gave the highest callus fresh weight followed by those
      contained 2 mg L-1 zeatin then that cultured on 4 mg L-1 zeatin. Data reported as
      Mean+/-Standard Deviation (SD). Data were subjected to one-way analysis of
      variance (p< 0.05). Results were processed by Excel (2010) and SPSS Version 17.0.
      RESULTS: It was found that callus growing on medium supplemented with 4 mg L-1
      zeatin gave the maximum value (14.93%) of yield extract. Callus cultured on 4 mg
      L-1 zeatin recorded the maximum total phenol (268.33 mg GAE/100 g FW of callus)
      and total flavonoids (2703.33 MUg QE/100 g FW of callus) accumulation. The
      antioxidant activity of each extract was determined through DPPH radical
      scavenging activity. Callus cultured on 4 mg L-1 TDZ showed the highest
      antioxidant activity then those cultured on 4 mg L-1 zeatin. The HPLC analysis
      for phenolic acids showed that chlorogenic acid, rosmarinic acid and cinnamic
      reached their highest contents with callus cultured on 4 mg L-1 TDZ (123.24,
      322.14 and 278.22 MUg g-1, respectively). Regarding flavonoids and using HPLC
      analysis, rutin, apigenin-7-glucoside and kaempferol were detected. Callus
      cultured with 4 mg L-1 TDZ gave the highest rutin and kaempferol contents (287.76
      and 10.38 MUg g-1, respectively). However, apigenin-7-glucoside was detected with
      high content (129.86 MUg g-1) in callus culture with 4 mg L-1 Zeatin. CONCLUSION:
      The HPLC analysis recommended that TDZ is more effective in accumulation of
      individual phenolic and flavonoid than Zeatin. The present study provided a
      useful system for further study on in vitro culture of G. jasminoides as
      alternative and new source for important secondary products.

PMID- 29023065
TI  - Enzyme Digestive Activities During Ontogeny in Marosatherina ladigesi Larvae.
AB  - BACKGROUND AND OBJECTIVE: Marosatherina ladigesi, including native fish in South
      Sulawesi Indonesia, are vulnerable and must be preserved. The objective of the
      study was to examine known food consumption, survival, growth and the activities
      of digestive enzymes of M. ladigesi larvae. MATERIAL AND METHODS: The larvae were
      obtained from natural spawning and the mixed live feed: Infusoria sp., Daphnia
      sp. and Artemia salina were given twice a day. Feed intake, growth, survival,
      activities of protease, lipase and amylase enzymes were observed in ages 3, 5,
      10, 15, 20, 25, 30, 35 Days after Hatching (DAH). Data were analyzed by following
      a complete randomized trial design. RESULTS: Activities of protease, amylase and
      lipase enzymes have been detected since 3 DAH. The protease enzyme activity was
      obtained at 0.438 U mL min-1 at 35 DAH, while amylase and lipase activities
      fluctuated. Activities of amylase and lipase reached 0105 and 0.093 U mL-1 min-1
      at 15 DAH, respectively. The activity of the enzyme increased at the same age of
      10-15 DAH larvae entering a phase of flexion. CONCLUSION: It was concluded that
      the use of mixed live feed Infusoria sp., Daphnia sp. and A. salina contribute to
      enzyme protease, lipase and amylase activities during the ontogeny stages of M.
      ladigesi. The highest activity of protease suggests that the fish have
      carnivorous feeding habits. The results of this study can be used to improve the
      maintenance technique of M. ladigesi larvae in order to accelerate growth and
      improve survival as an effort to increase the production of M. ladigesi.

PMID- 29023066
TI  - alpha-globin Alteration in alpha-thalassemia Disorder: Prediction and Interaction
      Defect.
AB  - BACKGROUND AND OBJECTIVE: The alpha-thalassemia is an inherited blood disorder
      affecting quality and quantity of hemoglobin. It caused mostly by deletion of one
      or two alpha-globin genes and characterized by deficient production of alpha
      globin chain in hemoglobin leading from mild anemia to lethal. The alpha-globin
      gene with partial deletion could reduce chain production or produce abnormal
      chain. Its effect depends on mechanism of chain production affected. This study
      aimed to analyze the effect of partial deletion in alpha-globin gene influencing
      the mechanisms to produce functional alpha-globin chain in alpha-thalassemia
      cases. MATERIALS AND METHOD: The three mutant genes from genebank were selected
      and processed. The analysis performed in deleted sequences determination, mRNA
      sequences, protein structures and protein chains interaction to form hemoglobin
      by SWISS MODEL, CHIMERA and SABLE Polyview 2D. RESULTS: The result showed 76
      amino acids deleted in one mutant alpha-globin gene (V00516.1). The mutation gave
      effect in every mechanism of the alpha-globin chain conformation and production.
      It affected protein conformation by losing over half the helical chains. It
      reduced the function completely, in which, disturb hemoglobin A (HbA) production
      with emergence of beta-sheets conformation. CONCLUSION: The analysis concluded
      that the protein produced by the alpha-globin gene with partial deletion lost its
      function and unable to form hemoglobin.

PMID- 29023067
TI  - Studies on Staphylococcus aureus Isolated from Pimples.
AB  - BACKGROUND AND OBJECTIVE: Pimples (acne) are small skin lesions or inflammations
      of the skin. The most common factor causing acne is the hormonal changes that
      occur during adolescent and teenage years. Antibiotics are becoming less
      effective in the treatment of pimples due to increasing concerns of antibiotic
      resistance. This study was therefore carried out to characterize the isolates
      from the pimples of Covenant University Students and to determine their
      antibiotics sensitivity pattern. MATERIALS AND METHODS: A total of 20 swab
      samples were obtained from male and female students with obvious signs of pimples
      in Covenant University, Ota, Ogun State, Nigeria. The samples obtained were
      cultured on Mannitol Salt Agar and incubated at 37 degrees C. Pure isolates
      obtained were subjected to Gram staining and other biochemical tests for
      identification. The isolates were further subjected to antibiotics sensitivity
      tests using antibiotic dics. RESULTS: Macroscopic examination indicated that the
      organisms were convex, smooth and shiny. Microscopic examination revealed that
      the isolates were positive after employing the Gram Staining technique and they
      appeared as grape-like clusters. Biochemical tests revealed that the isolates
      were Coagulase positive, Catalase positive, Urease positive, Citrate positive,
      Methyl-Red positive, Voges-Proskauer negative and negative upon starch
      hydrolysis. The sugar fermentation tests revealed that the isolates fermented
      Glucose, Maltose, Galactose, Sucrose and Lactose, respectively. The antibiotic
      susceptibility test showed that isolates were resistant to Cotrimazole,
      Cloxacillin, Erythromycin, Gentamycin, Augmentin, Streptomycin, Tetracycline and
      Chloramphenicol. CONCLUSION: The results therefore indicated that the isolates
      were Staphylococcus aureus and other staphylococci species. Indiscriminate use of
      antibiotics should be avoided to prevent the development of resistant strains of
      the Staphylococci genera and other pathogenic organisms.

PMID- 29023068
TI  - Zeatin and Thidiazuron Induced Embryogenic Calli From In Vitro Leaf and Stem of
      Jojoba (Simmondsia chinensis).
AB  - BACKGROUND AND OBJECTIVE: Jojoba is a promising industrial plant, which
      recommended with pharmaceutical benefits. The present study was conducted to
      stimulate embryogenic calli formation from jojoba using zeatin and thidiazuron
      (TDZ), as well as determination of the antioxidant activity of proliferated
      calli. MATERIALS AND METHODS: For callus induction, leaf and stem explants
      derived from in vitro grown shootlets, were cultured on Murashige and Skoog (MS)
      medium with different combinations of 0.5 mg L-1 benzyl adenine (BA) or kinetin
      with 2,4-Dichlorophenoxyacetic acid (2,4-D), Naphthalene acetic acid (NAA) and
      picloram at 0.5 or 1mg L-1. To stimulate embryogenic calli, friable callus were
      transferred to woody plant medium (WPM) supplemented with different
      concentrations of zeatin or TDZ. Antioxidant activity of different treatments was
      determined using hexane or petroleum ether extraction. Data was analyzed as
      mean+/-standard deviation (SD). RESULTS: The MS medium supplemented with 0.5 mg L
      1 BA+0.5 or 1 mg L-1 picloram was the best treatment to obtain friable calli from
      both explants types. WPM medium supplemented with 2 mg L-1 zeatin gave the
      highest percentage of embryogenic calli derived from leaf explants. While the
      highest percentage of embryogenic calli derived from stem explants was registered
      using 1 or 4 mg L-1 TDZ containing medium. Embryogenic calli originated from
      leaves explants on 1.5 mg L-1 zeatin showed promising activity of antioxidant
      with hexane extraction. However, embryogenic calli originated from stem explants
      on 1 mg L-1 TDZ showed the highest antioxidant activity with petroleum ether
      extraction. CONCLUSION: TDZ has promising effect on embryogenic callus induction
      from stem explants. While, zeatin has promising effect on embryogenic callus
      induction from leaf explants.

PMID- 29023069
TI  - Histological Characteristics on the Testes of Mud Spiny Lobster, Panulirus
      polyphagus (Herbst, 1793).
AB  - BACKGROUND AND OBJECTIVE: Mud spiny lobsters, Panulirus polyphagus (P.
      polyphagus) are one of the most important fisheries resources now-a-days due to
      quality that it's possessed. However, there is still lack of in-depth study about
      this species mainly on males testicular characteristics and sexual maturity size.
      Therefore, the present study was carried out to investigate the histological
      characteristics on the testes and sexual maturity sizes of mud spiny lobster,
      Panulirus polyphagus. MATERIALS AND METHODS: The testes were dissected out and
      fixed in 10% buffered formalin solution for 11 h, dehydrated in 70% alcohol and
      lastly placed in tissue processor for 18+/-1 h at 60 degrees C. The tissues
      blocks were cut at the thickness of 4 MUm on a rotary microtome. Stained tissues
      were taken under Advance Microscope (Nikon Eclipse 80i Nomarski DIC). Collected
      data were analyzed using Microsoft Excel 2013. Data were presented as mean+/
      standard deviation. Statistical analyses were done using one-way ANOVA using SPSS
      (Version 22). RESULTS: These lobules of mature P. polyphagus were formed via
      different germinative lineage cells such as spermatogonia, spermatocytes,
      spermatids and spermatozoa. The histological characteristics of testes showed
      that the process of spermatogenesis went through the stages of four testes
      maturation which were spermatogonia I and II, spermatocytes I and II, spermatids
      and spermatozoa stages within different body weight of P. polyphagus. It was
      found that there were significant difference between body weight and carapace
      length to the testicular maturation stages (one-way ANOVA and p = 0.000).
      CONCLUSION: The results of this experiment indicated that males P. polyphagus
      have four stages of testes maturation and can be considered to have fully mature
      testes that ready for fertilization at 452 g body weight (BW) and 107 mm carapace
      length (CL) or more.

PMID- 29023070
TI  - Effect of some Evaporation Matters on Storability of Sunflower ( Helianthus
      annuus L.) Seed.
AB  - BACKGROUND AND OBJECTIVE: This study focuses on finding compounds that are safe
      to humans and environment, such as propionic and acetic acids that may provide an
      alternative control of seed-borne pathogens and decrease seed deterioration
      during storage. The objectives of this study were to reduce sunflower seed
      deterioration and improve the viability of sunflower seed using environmentally
      safe organic acids. MATERIALS AND METHODS: Propionic and acetic acids were
      applied on sunflower seed at different concentrations under laboratory conditions
      during different storage periods. After 6 months storage period, the viability of
      sunflower seed as well as morphological and physiological characteristics of
      seedlings were evaluated under greenhouse conditions. Laboratory experiment was
      conducted in a factorial completely randomized design and randomized complete
      block design for greenhouse experiment. RESULTS: Propionic and acetic acids at
      different concentrations showed inhibitory effects on the presence of different
      fungal genera in all storage periods. Propionic acid was most effective followed
      by acetic acid. Increasing storage periods from 0-6 months significantly
      decreased germination percentage, germination energy, seedling characters,
      survived healthy seedlings and seed oil and protein percentages but dead and
      rotted seeds, as well as rotted seedlings were increased. Treating sunflower
      seeds with propionic acid (100%) improved germination criteria, seedling
      characters and seed chemical characters as well as survival seedlings and
      minimized the dead seeds, rotted seeds and rotted seedlings as compared with the
      control under all storage periods. Under greenhouse conditions, the maximum
      growth parameter and physiological characters (chlorophylls a, b, carotenoids and
      total phenols) were recorded from seed treated with 100% propionic acid after 6
      months of storage. CONCLUSION: It may be concluded that propionic and acetic
      acids vapors can have considerable fungicidal activity against sunflower
      pathogens and improve seed viability. Therefore, it is recommended using 100%
      propionic acid to reduce deterioration and seed-borne pathogens of sunflower
      under storage conditions.

PMID- 29023071
TI  - Enhancement of a Novel Isolate of Serratia plymuthica as Potential Candidate for
      an Antianthracnose.
AB  - BACKGROUND AND OBJECTIVE: A new rhizobacteria isolate of Serratia plymuthica
      (strain UBCR_12) exhibited a promising potential as a biocontrol agent for
      anthracnose causing agent Colletotrichum gloeosporioides. The aim of this study
      was to characterize its antagonistic activity and explore the factors
      contributing to a higher inhibition activity. MATERIALS AND METHODS: The
      antifungal effect of UBCR_12 against C. gloeosporioides was assayed under various
      pH values and nutritional sources. Culture supernatant obtained from UBCR_12 and
      C. gloeosporioides co-culture was also tested for its inhibitory activity. In
      addition, the antagonistic range of this isolate was examined against Sclerotium
      rolfsii and Fusarium oxysporum. Statistical analysis was done using one way
      analysis of variance and further processed using Fisher's Least Significant
      Difference (LSD) test with a p<0.05. RESULTS: The UBCR_12 induced inhibition was
      shown to be stable over time at pH 7, while peptone addition led to a faster
      induction (2 days after treatment) and glucose treatment to a higher activity. Of
      all these modifications, preliminary co-culture experiments with fungal cells
      resulted in the best antagonistic activity of UBCR_12 culture supernatant of
      about 30.66%. This isolate also showed a wide range of antagonistic activity due
      to its high suppression against S. rolfsii and F. oxysporum from soybean.
      CONCLUSION: Both environmental and biotic manipulations contributed an elevated
      inhibition rate of UBCR_12 against C. gloeosporioides. A proportional combination
      of the factors stimulating antagonistic activity of this strain is recommended to
      be utilized for the development of this strain as an antianthracnose. The
      enhanced antifungal effects of UBCR_12 resulted under each type of modification
      were varied indicating the difference of cell responses. It suggests that certain
      antifungal mechanism could be generated by modifying the environmental factor
      required for its induction. In addition, the application of cell-free culture
      supernatant provides an alternative solution in the utilization of biocontrol
      agents. For large scale application, it could minimize the risk of population
      outbreaks and harmful effects due to the living cells application.

PMID- 29023072
TI  - Toxicity of Cypermethrin and Chlorpyrifos Against German Cockroach [ Blattella
      germanica (Blattaria: Blattellidae)] Strains from Hamadan, Iran.
AB  - BACKGROUND: German cockroach has relatively short life cycle and reproduce
      rapidly. It is the most common medically and public health pest. As a result, it
      is essential to combat this pest. Cypermethrin and chlorpyrifos are used by
      private companies in Hamadan to control Blattella germanica. It seems necessary
      to determine its susceptibility levels to these insecticides. OBJECTIVE: The aim
      of this study was to determine the susceptibility levels of B. germanica strains
      to cypermethrin and chlorpyrifos in Hamadan. MATERIALS AND METHODS: In this
      study, the German cockroach strains were collected from two hospitals (Fatemiyeh
      and Atiyeh) in Hamadan and transfered to the insectarium. The cockroach strains
      were reared under the same laboratory condition. Then their sensitivity levels
      were considered to 1, 2, 4, 8 and 16 mg m -2 for cypermethrin and 0.82, 1.65,
      3.31, 6.63, 9.945 and 13.26 mg m -2 for chlorpyrifos using surface contact
      method. RESULTS: Results based on insecticide treated doses, B. germanica strains
      showed different percent mortality to the insecticides ranged from 13.3-100. The
      LD 50 and LD 90 and regression lines of the treated insecticides against German
      cockroach strains indicate that Fatemiyeh Hospital strain is more susceptible to
      the treated insecticides than Atiyeh Hospital strain. The LD 50 and LD 90 of
      chlorpyrifos are also lower than cypermethrin, indicated that chlorpyrifos is
      more effective than cypermethrin against German cockroach. As the slopes of the
      regression lines are observed mild in this study indicate that the population of
      the cockroach strains is very heterogeneous. It can be a symbol of insecticides
      resistance to cypermethrin and chlorpyrifos. CONCLUSION: As chlorpyrifos and
      cypermethrin insecticides are also used for residual spraying by private
      companies and the doses which provide more than 90% mortality are below the WHO
      recommended insecticide doses. Therefore, chlorpyrifos and cypermethrin
      insecticides can be used for B. germanica control in Hamadan within regular
      monitoring and preventive measures of resistance.

PMID- 29023073
TI  - Reproductive Biology of Sardinella sp. (Sardinella aurita and Sardinella
      maderensis) in the South of Morocco.
AB  - BACKGROUND AND OBJECTIVE: Sardinella sp. has gained much attention lately because
      of its biomass increase, which might be the result of climatic changes occurring
      across the Atlantic sea. Little information is known about reproduction of these
      species particularly in the Moroccan Atlantic area. The objective of the this
      study was to explore some aspects of the reproductive biology of Sardinella in
      the South of Atlantic Moroccan coast. MATERIALS AND METHODS: Monthly samples were
      collected during the period between February, 2015 and January, 2016 in the area
      between Cape Boujdor and Cape Blanc. The data collected concerned the measure of
      the total length, the weight, the gonad weight as well as the sex and maturity
      stages. The chi2 test was used to compare the differences between both sexes and
      the ANOVA test was adopted to analyze the data variation. RESULTS: Sardinella sp.
      is a gonochoristic fish. The overall female to male ratio was not statistically
      different for both species (chi2 = 0.68 for Sardinella aurita and chi2 = 1.04 for
      Sardinella maderensis), although it varied seasonally and according to the length
      of the fish. The monthly changes in the gonadosomatic index and the macroscopic
      characteristics of gonads showed that round Sardinella in the South of Morocco
      spawns between February and July and between November and December with a
      spawning peak on April. For the flat Sardinella, it spawns between February and
      March and in July with a spawning peak on July. Females round Sardinella reach
      first sexual maturity at a smaller size than males (26.17 and 26.78 cm,
      respectively). Concerning the flat Sardinella, it was the opposite. Males
      reaching sexual maturity are smaller than females (20.75 and 21.76 cm,
      respectively). CONCLUSION: It is concluded that the size at first maturity
      revealed that mature females in the South of Moroccan Atlantic Ocean were smaller
      than males for the round Sardinella and the opposite was observed for the flat
      Sardinella. The spawning of S. aurita presented a pick in April and for S.
      maderensis in July. As a shared stock these findings will be used for stock
      assessment in the North West Africa area.

PMID- 29023074
TI  - Bacterial Quality of Urinary Tract Infections in Diabetic and Non Diabetics of
      the Population of Ma'an Province, Jordan.
AB  - BACKGROUND AND OBJECTIVE: The patients with Diabetes Mellitus (DM) have
      malfunction in bladder which prompt urine accumulation in its pool which serves a
      decent situation to the microbes to be develop and cause Urinary Tract Infection
      (UTI). The UTI is the most infectious disease that affects both males and
      females. This study was designed to detect the bacterial species responsible for
      UTI in both diabetic and non-diabetic patients in Ma'an province, Jordan.
      MATERIALS AND METHODS: One hundred sixteen urine samples were investigated to
      determine UTI-causing bacteria. These samples distributed unequally between
      diabetic male (12) and diabetic female (25) and also non-diabetic male (13) and
      non-diabetic female (66). RESULTS: It was observed that E. coli is responsible
      for large proportion (44.8%) of UTI in both diabetic (15.5%) and non-diabetic
      (29.3%) patients. This study showed inequality in the bacterial species that were
      isolated from both diabetic and non-diabetic samples. However, five bacterial
      species including E. aerogenes, E. cloacae, C. freundii, A. baumannii and B.
      subtilis did not exist in all diabetic samples. Treatment of UTI in both diabetic
      and non-diabetic patients with chloramphenicol (30 MUg), ciprofloxacin (5 MUg)
      and vancomycin (30 MUg) resulted in more favorability than other antibiotics. At
      the same time cephalothin (30 MUg) was not recommended. CONCLUSION: Escherichia
      coli was the prevailing bacterial infections among those which were isolated from
      patients with UTI. Certain forms of bacterial infections inclined to be extra
      common in diabetic patients than others and other infections may be more severe
      in people with diabetics than in non diabetics.

PMID- 29023075
TI  - Evaluation of MiR-21 and MiR-10b Expression of Human Breast Cancer in West
      Sumatera.
AB  - BACKGROUND: Abnormal expression of several microRNAs (miRNAs) has been
      demonstrated in many types of cancer tumor tissue. The miR-10b and miR-21 are an
      oncogenic miRNAs which play role in proliferation and invasion of Breast Cancer
      (BC) tumorigenesis. The aim of this study was to evaluate the miR-21 and miR-10b
      expression in BC in West Sumatran women, Indonesia. MATERIALS AND METHODS: A
      total of 40 samples, consisting of 30 samples of breast cancer tissues (BC) and
      10 samples of fibroadenoma tissues (FATs) as control and non-cancerous were
      analyzed. The miR-21 and miR-10b expression of each sample were investigated by
      using realtime PCR, followed by universal Reverse Transcription (RT) then real
      time PCR amplification with specific primers. Hsa-miR-16-5p LNA PCR primer was
      used as an endogenous control. RESULTS: The results showed that the expression
      level of miR-21 was more than 4 times higher in BC than in FATs. The expression
      level of miR-10b was lower in BC than FATs, by a factor of 3.34 fold. Both these
      differences were statistically different (p = 0.001). CONCLUSION: In this study
      it was concluded that for this sample of West Sumatran Women miR-21 expression in
      BC was higher than in FATs, whereas miR-10b was lower in BC than in FATs.

PMID- 29023076
TI  - Flavonoid Production, Growth and Differentiation of Stelechocarpus burahol (Bl.)
      Hook. F. and Th. Cell Suspension Culture.
AB  - BACKGROUND AND OBJECTIVE: Stelechocarpus burahol is a plant containing flavonoid
      compounds that have the potential for use as an antihyperuricemic for gout
      medication. This study was performed to assess flavonoid production, growth and
      cell differentiation of S. burahol in cell suspension culture. METHODOLOGY:
      Mesocarp was planted in Murashige and Skoog (MS) medium supplemented with 7.5 mg
      L-1 picloram for the induction of callus. Non-embryonic callus obtained was used
      in the formation of cell suspension cultures. Growth of cells was determined by
      fresh and dry weights. During the culturing, the fresh weight, dry weight and
      flavonoid content were determined as a result of culture status. RESULTS: The
      growth of the S. burahol cell suspension was slow, the stationary phase occurred
      at 30 days. The production of flavonoids was not in line with the growth of cells
      and the maximum production occurred on the 15th day of the log phase. The
      globular-shaped cells dominated the cell suspension culture at all ages.
      Fluorescein diacetate (FDA) staining of cells derived from cell cultures aged for
      36 days showed that some cells were still viable. CONCLUSION: The results show
      that flavonoid production, growth and cell differentiation of a S. burahol cell
      suspension culture differed according to the culture age.

PMID- 29023077
TI  - Spermatogenic and Phylo-molecular Characterizations of Isolated Fasciola Spp.
      From Cattle, North West Iran.
AB  - BACKGROUND AND OBJECTIVE: Fascioliasis is economically important to the livestock
      industry that caused with Fasciola hepatica and Fasciola gigantica. The objective
      of this study was to identify these two species F. hepatica and F. gigantica by
      using nuclear and mitochondrial markers (ITS1, ND1 and CO1) and have been
      employed to analyze intraspecific phylogenetic relations of Fasciola spp.
      MATERIALS AND METHODS: Approximately 150 Fasciola specimens were collected, then
      stained with haematoxylin-carmine dye and observed under an optical microscope to
      examine for the existence of sperm. The ITS1 marker was used to identify
      different Fasciola and phylogenetic analysis based on ND1 and CO1 sequence data
      were conducted by maximum likelihood algorithm. RESULTS: Fasciola samples were
      separated into 2 groups. Almost all specimens had many sperms in the seminal
      vesicle (spermic fluke) and one fluke did not contain any sperm in the seminal
      vesicle. The aspermic sample had F. gigantica RFLP pattern with ITS1 gene.
      Phylogenetic analysis based on NDI and COI sequence data were conducted by
      maximum likelihood showed a similar topology of the trees obtained particularly
      for F. hepatica and F. gigantica. CONCLUSION: This study demonstrated that
      aspermic Fasciola found in this region of Iran has same genetic structures
      through the spermic F. gigantica populations in accordance to phylogenetic tree.

PMID- 29023079
TI  - Risk of acute STEMI significantly increased in younger smokers.

PMID- 29023078
TI  - Polymorphism of Insulin-like Growth Factor 1 Gene (IGF1/TasI, IGF1/SnaBI,
      IGF1/RsaI) and the Association with Daily Gain of Pesisir Cattle Local Breed from
      West Sumatera, Indonesia.
AB  - BACKGROUND AND OBJECTIVE: The insulin-like growth factor 1 gene (IGF1) is a
      candidate gene for marker-assisted selection strategies. Two single nucleotide
      polymorphism of IGF1 gene namely IGF1/SnaBI and IGF1/TasI has been reported to be
      associated with production traits in several cattle breeds. One single nucleotide
      polymorphism in exon 4 namely IGF1/Rsa1 has a significant influence (p<0.01) on
      birth weight, weaning weight and average daily gain of Bali cattle. The objective
      of this study was to determine the IGF1/SnaBI, IGF1/TasI and IGF1/RsaI
      polymorphisms and their associations with average daily gain in Pesisir cattle
      local breed from west Sumatera Indonesia. METHODOLOGY: The isolation of DNA from
      183 blood sample was performed using DNA extraction kit (Promega DNA purification
      kit) following the manufacture procedure. The amplification of IGF1 fragment was
      done by master mix from Thermo Scientific. RESULTS: In the case of the IGF1/SnaBI
      polymorphism, three genotypes were observed, frequencies were 0.011, 0.011 and
      0.978 for AA, AB and BB, respectively. This gives frequencies of 0.064 and 0.9836
      for A and B alleles. For IGF1-TasI locus showed that AA genotype occurred with a
      frequency of 0.978, AC with 0.011 and CC with 0.011 with frequency for allele A
      and C were 0.9836 and 0.0164, respectively. In the case IGF1/RsaI polymorphism
      produces only TT and CT genotype with frequency 0.027 and 0.973 respectively and
      frequency of T and C allele were 0.5137 and 0.4863, respectively. CONCLUSION:
      Among these 3 polymorphism only IGF1/RsaI was associated with average daily gain,
      Thus this polymorphism could be a potential for improving body weight in Pesisir
      cattle. Association study for IGF1/SnaBI and IGF1/TasI were strongly limited by
      low frequency of one allele.

PMID- 29023080
TI  - Depression is linked to dementia in older adults.
AB  - Depression and dementia are both common conditions in older people, and they
      frequently occur together. Late life depression affects about 3.0-4.5% of adults
      aged 65 and older. Depression occurs in up to 20% of patients with Alzheimer's
      disease and up to 45% of patients with vascular dementia. Rather than a risk
      factor, depression with onset in later life is more likely to be either prodromal
      to dementia or a condition that unmasks pre-existing cognitive impairment by
      compromising cognitive reserve. Depression can be a psychological response to
      receiving a diagnosis of dementia. The distinction between depression and early
      dementia may be particularly difficult. Detailed histories obtained from patients
      and their relatives as well as longitudinal follow-up are important. Cognitive
      testing can be very helpful. It is preferable to use a neuropsychological test
      that is sensitive to subtle cognitive changes and assesses all cognitive domains,
      such as the Montreal Cognitive Assessment. Older people with depression are at
      raised risk of dementia and this risk is increased if they have had symptoms for
      a long time, if their symptoms are severe, where there are multiple (vascular)
      comorbidities, and where there are structural brain changes including hippocampal
      atrophy and white matter abnormalities.

PMID- 29023081
TI  - Frailty predicts adverse outcomes in older people with diabetes.
AB  - The greatest proportional increase in the number of people with diabetes by age
      group is predicted to occur in those aged 60 to 79. In older people living with
      diabetes, geriatric syndromes, which indicate frailty, are emerging as a third
      category of complications in addition to the traditional microvascular and
      macrovascular sequelae. Frailty is defined by the presence of three or more
      phenotypes (weight loss, weakness, decreased physical activity, exhaustion and
      slow gait speed). The presence of one or two phenotypes describes a pre-frail
      state, and the absence of phenotypes describes a non-frail person. Sarcopenia, or
      loss of muscle mass, is the muscular manifestation of frailty phenotype and is
      defined as a generalised loss of skeletal muscle mass and strength that leads to
      low physical performance. Persistent hyperglycaemia has been shown to be
      associated with poor muscle quality, performance and strength independent of age,
      race, sex, weight, height and physical activity. The coexistence of dementia and
      diabetes also increases the risk of frailty. There is evidence that midlife
      behaviours such as smoking, alcohol consumption, poor diet and low levels of
      physical activity are associated with frailty and dementia in later life. Frailty
      is a dynamic condition which can worsen or improve over time. Patients may
      progress from a non-frail to pre-frail or frail state. With timely intervention,
      there is a greater chance for an individual to recover from pre-frail to non
      frail than to deteriorate into frailty. The progression of frailty is likely to
      be multifactorial, therefore multimodal intervention, including maintenance of
      adequate nutrition, physical exercise, and glycaemic control, may help to delay
      or prevent the development of frailty and to improve outcomes.

PMID- 29023087
TI  - Simulations of a Graphene Nanoflake as a Nanovector To Improve ZnPc Phototherapy
      Toxicity: From Vacuum to Cell Membrane.
AB  - We propose a new approach to improving photodynamic therapy (PDT) by transporting
      zinc phthalocyanine (ZnPc) in biological systems via a graphene nanoflake, to
      increase its targeting. Indeed, by means of time-dependent density functional
      theory simulations, we show that the ZnPc molecule in interaction with a graphene
      nanoflake preserves its optical properties not only in a vacuum but also in
      water. Moreover, molecular dynamic simulations demonstrate that the graphene
      nanoflake/ZnPc association, as a carrier, permits one to stabilize the
      ZnPc/graphene nanoflake system on the cellular membrane, which was not possible
      when using ZnPc alone. We finally conclude that the graphene nanoflake is a good
      candidate to transport and stabilize the ZnPc molecule near the cell membrane for
      a longer time than the isolated ZnPc molecule. In this way, the choice of the
      graphene nanoflake as a nanovector paves the way to ZnPc PDT improvement.

PMID- 29023082
TI  - Be vigilant for skin manifestations of inherited cancer syndromes.
AB  - More than 200 hereditary cancer susceptibility syndromes have been described, and
      it is thought that they account for 5-10% of all cancers. Many have
      dermatological manifestations (usually lesions, occasionally rashes) which
      frequently precede other systemic pathology. Dermatological signs are usually non
      specific and often trivial in appearance, making their significance easy to
      overlook and a clinical diagnosis challenging. Histological examination is often
      required to differentiate lesions. They are usually benign and pathologically
      unrelated to the primary tumours, with the exception of the atypical moles of the
      dysplastic naevus syndrome, and may present simply as a cosmetic problem for the
      patient. However, a number of cancer syndromes exhibit an increased risk of
      developing malignant skin lesions. For instance, Gorlin syndrome (nevoid basal
      cell carcinoma syndrome) which typically results in the development of multiple
      basal cell carcinomas, within the first few decades of life. The majority of
      cancer syndromes with skin signs are inherited in an autosomal dominant pattern
      demonstrating complete penetrance before the age of 70. Once a cancer syndrome
      has been diagnosed, the cornerstone of management is frequent surveillance for
      the early detection and treatment of malignancy. Genetic testing and counselling
      should be offered to family members.

PMID- 29023088
TI  - Strong Photoluminescence Enhancement in All-Dielectric Fano Metasurface with High
      Quality Factor.
AB  - All-dielectric metamaterials offer great flexibility for controlling light-matter
      interaction, owing to their strong electric and magnetic resonances with
      negligible loss at wavelengths above the material bandgap. Here, we propose an
      all-dielectric asymmetric metasurface structure exhibiting high quality factor
      and prominent Fano line shape. Over three-orders photoluminescence enhancement is
      demonstrated in the fabricated all-dielectric metasurface with record-high
      quality factor of 1011. We find this strong emission enhancement is attributed to
      the coherent Fano resonances, which originate from the destructive interferences
      of antisymmetric displacement currents in the asymmetric all-dielectric
      metasurface. Our observations show a promising approach to realize light emitters
      based on all-dielectric metasurfaces.

PMID- 29023090
TI  - Comment on "Resource Footprints are Good Proxies of Environmental Damage".

PMID- 29023089
TI  - Gelatin-Polyaniline Composite Nanofibers Enhanced Excitation-Contraction Coupling
      System Maturation in Myotubes.
AB  - In this study, composite gelatin-polyaniline (PANI) nanofibers doped with
      camphorsulfonic acid (CSA) were fabricated by electrospinning and used as
      substrates to culture C2C12 myoblast cells. We observed enhanced myotube
      formation on composite gelatin-PANI nanofibers compared to gelatin nanofibers,
      concomitantly with enhanced myotube maturation. Thus, in myotubes, intracellular
      organization, colocalization of the dihydropyridine receptor (DHPR) and ryanodine
      receptor (RyR), expression of genes correlated to the excitation-contraction (E
      C) coupling apparatus, calcium transients, and myotube contractibility were
      increased. Such composite material scaffolds combining topographical and
      electrically conductive cues may be useful to direct skeletal muscle cell
      organization and to improve cellular maturation, functionality, and tissue
      formation.

PMID- 29023091
TI  - Correction to "Detection of Orexin A Neuropeptide in Biological Fluids Using a
      Zinc Oxide Field Effect Transistor".

PMID- 29023092
TI  - Effect of the Flexible Regions of the Oncoprotein Mouse Double Minute X on
      Inhibitor Binding Affinity.
AB  - The oncoprotein MdmX (mouse double minute X) is highly homologous to Mdm2 (mouse
      double minute 2) in terms of their amino acid sequences and three-dimensional
      conformations, but Mdm2 inhibitors exhibit very weak affinity for MdmX, providing
      an excellent model for exploring how protein conformation distinguishes and
      alters inhibitor binding. The intrinsic conformation flexibility of proteins
      plays pivotal roles in determining and predicting the binding properties and the
      design of inhibitors. Although the molecular dynamics simulation approach enables
      us to understand protein-ligand interactions, the mechanism underlying how a
      flexible binding pocket adapts an inhibitor has been less explored
      experimentally. In this work, we have investigated how the intrinsic flexible
      regions of the N-terminal domain of MdmX (N-MdmX) affect the affinity of the Mdm2
      inhibitor nutlin-3a using protein engineering. Guided by heteronuclear nuclear
      Overhauser effect measurements, we identified the flexible regions that affect
      inhibitor binding affinity around the ligand-binding pocket on N-MdmX. A
      disulfide engineering mutant, N-MdmXC25-C110/C76-C88, which incorporated two
      staples to rigidify the ligand-binding pocket, allowed an affinity for nutlin-3a
      higher than that of wild-type N-MdmX (Kd ~ 0.48 vs Kd ~ 20.3 MUM). Therefore,
      this mutant provides not only an effective protein model for screening and
      designing of MdmX inhibitors but also a valuable clue for enhancing the
      intermolecular interactions of the pharmacophores of a ligand with pronounced
      flexible regions. In addition, our results revealed an allosteric ligand-binding
      mechanism of N-MdmX in which the ligand initially interacts with a compact core,
      followed by augmenting intermolecular interactions with intrinsic flexible
      regions. This strategy should also be applicable to many other protein targets to
      accelerate drug discovery.

PMID- 29023094
TI  - High-Speed Atomic Force Microscopy Visualization of the Dynamics of the
      Multienzyme Fatty Acid Synthase.
AB  - Multienzymes, such as the protein metazoan fatty acid synthase (FAS), are giant
      and highly dynamic molecular machines for critical biosynthetic processes. The
      molecular architecture of FAS was elucidated by static high-resolution
      crystallographic analysis, while electron microscopy revealed large-scale
      conformational variability in FAS with some correlation to functional states in
      catalysis. However, little is known about time scales of conformational dynamics,
      the trajectory of motions in individual FAS molecules, and the extent of coupling
      between catalysis and structural changes. Here, we present an experimental single
      molecule approach to film immobilized or selectively tethered FAS in solution at
      different viewing angles and high spatiotemporal resolution using high-speed
      atomic force microscopy. Mobility of individual regions of the multienzyme is
      recognized in video sequences, and correlation of shape features implies a
      convergence of temporal resolution and velocity of FAS dynamics. Conformational
      variety can be identified and grouped by reference-free 2D class averaging,
      enabling the tracking of conformational transitions in movies. The approach
      presented here is suited for comprehensive studies of the dynamics of FAS and
      other multienzymes in aqueous solution at the single-molecule level.

PMID- 29023095
TI  - Capacitive Sensing of Glucose in Electrolytes Using Graphene Quantum Capacitance
      Varactors.
AB  - A novel graphene-based variable capacitor (varactor) that senses glucose based on
      the quantum capacitance effect was successfully developed. The sensor utilizes a
      metal-oxide-graphene varactor device structure that is inherently compatible with
      passive wireless sensing, a key advantage for in vivo glucose sensing. The
      graphene varactors were functionalized with pyrene-1-boronic acid (PBA) by self
      assembly driven by pi-pi interactions. Successful surface functionalization was
      confirmed by both Raman spectroscopy and capacitance-voltage characterization of
      the devices. Through glucose binding to the PBA, the glucose concentration in the
      buffer solutions modulates the level of electrostatic doping of the graphene
      surface to different degrees, which leads to capacitance changes and Dirac
      voltage shifts. These responses to the glucose concentration were shown to be
      reproducible and reversible over multiple measurement cycles, suggesting promise
      for eventual use in wireless glucose monitoring.

PMID- 29023093
TI  - A Fluorescent Probe with Improved Water Solubility Permits the Analysis of
      Protein S-Depalmitoylation Activity in Live Cells.
AB  - S-Palmitoylation is an abundant lipid post-translational modification that is
      dynamically installed on and removed from target proteins to regulate their
      activity and cellular localization. A dearth of tools for studying the activities
      and regulation of protein S-depalmitoylases, thioesterase "erasers" of protein
      cysteine S-palmitoylation, has contributed to an incomplete understanding of the
      role of dynamic S-palmitoylation in regulating proteome lipidation. Recently, we
      developed "depalmitoylation probes" (DPPs), small molecule probes that become
      fluorescent upon S-depalmitoylase enzymatic activity. To be suitable for
      application in live cells, the first-generation DPPs relied on a shorter lipid
      substrate (C8 vs naturally occurring C16), which enhanced solubility and cell
      permeability. However, the use of an unnatural lipid substrate on the probes
      potentially limits the utility of the approach. Herein, we present a new member
      of the DPP family, DPP-5, which features an anionic carboxylate functional group
      that increases the probe water solubility. The enhanced water solubility of DPP-5
      permits the use of a natural, palmitoylated substrate (C16), rather than a
      surrogate lipid. We show that DPP-5 is capable of monitoring endogenous S
      depalmitoylases in live mammalian cells and that it can reveal changes in S
      depalmitoylation levels due to lipid stress. DPP-5 should prove to be a useful
      new tool for probing the regulation of proteome lipidation through dynamic S
      depalmitoylation.

PMID- 29023096
TI  - Graphene Liquid Enclosure for Single-Molecule Analysis of Membrane Proteins in
      Whole Cells Using Electron Microscopy.
AB  - Membrane proteins govern many important functions in cells via dynamic
      oligomerization into active complexes. However, analytical methods to study their
      distribution and functional state in relation to the cellular structure are
      currently limited. Here, we introduce a technique for studying single-membrane
      proteins within their native context of the intact plasma membrane. SKBR3 breast
      cancer cells were grown on silicon microchips with thin silicon nitride windows.
      The cells were fixed, and the epidermal growth factor receptor ErbB2 was
      specifically labeled with quantum dot (QD) nanoparticles. For correlative
      fluorescence- and liquid-phase electron microscopy, we enclosed the liquid
      samples by chemical vapor deposited (CVD) graphene films. Depending on the local
      cell thickness, QD labels were imaged with a spatial resolution of 2 nm at a low
      electron dose. The distribution and stoichiometric assembly of ErbB2 receptors
      were determined at several different cellular locations, including tunneling
      nanotubes, where we found higher levels of homodimerization at the connecting
      sites. This experimental approach is applicable to a wide range of cell lines and
      membrane proteins and particularly suitable for studies involving both inter- and
      intracellular heterogeneity in protein distribution and expression.

PMID- 29023097
TI  - Isolation and Characterization of Few-Layer Manganese Thiophosphite.
AB  - This work reports an experimental study on an antiferromagnetic honeycomb lattice
      of MnPS3 that couples the valley degree of freedom to a macroscopic
      antiferromagnetic order. The crystal structure of MnPS3 is identified by high
      resolution scanning transmission electron microscopy. Layer-dependent angle
      resolved polarized Raman fingerprints of the MnPS3 crystal are obtained, and the
      Raman peak at 383 cm-1 exhibits 100% polarity. Temperature dependences of
      anisotropic magnetic susceptibility of the MnPS3 crystal are measured in a
      superconducting quantum interference device. Anisotropic behaviors of the
      magnetic moment are explored on the basis of the mean field approximation model.
      Ambipolar electronic conducting channels in MnPS3 are realized by the liquid
      gating technique. The conducting channel of MnPS3 offers a platform for exploring
      the spin/valleytronics and magnetic orders in 2D limitation.

PMID- 29023098
TI  - Multigenerational Effects of the Antibiotic Tetracycline on Transcriptional
      Responses of Daphnia magna and Its Relationship to Higher Levels of Biological
      Organizations.
AB  - Given the risk of environmental pollution by pharmaceutical compounds and the
      effects of these compounds on exposed ecosystems, ecologically relevant and
      realistic assessments are required. However, many studies have been mostly
      focused on individual responses in a single generation exposed to one-effect
      concentrations. Here, transcriptional responses of the crustacean Daphnia magna
      to the antibiotic tetracycline across multiple generations and effect
      concentrations were investigated. The results demonstrated that tetracycline
      induced different transcriptional responses of daphnids that were dependent on
      dose and generation. For example, reproduction-related expressed sequence tags
      (ESTs), including vitellogenin, were distinctly related to the dose-dependent
      tetracycline exposure, whereas multigenerational exposure induced significant
      change of molting-related ESTs such as cuticle protein. A total of 65 ESTs were
      shared in all contrasts, suggesting a conserved mechanism of tetracycline
      toxicity regardless of exposure concentration or time. Most of them were
      associated with general stress responses including translation, protein and
      carbohydrate metabolism, and oxidative phosphorylation. In addition, effects
      across the dose-response curve showed higher correlative connections among
      transcriptional, physiological, and individual responses than multigenerational
      effects. In the multigenerational exposure, the connectivity between adjacent
      generations decreased with increasing generation number. The results clearly
      highlight that exposure concentration and time trigger different mechanisms and
      functions, providing further evidence that multigenerational and dose-response
      effects cannot be neglected in environmental risk assessment.

PMID- 29023099
TI  - Fabrication of Novel Electrochemical Biosensor Based on Graphene Nanohybrid to
      Detect H2O2 Released from Living Cells with Ultrahigh Performance.
AB  - In this paper, a new class of metal-free nanocarbon catalyst-nitrogen (N) and
      sulfur (S) codoped graphene quantum dot/graphene (NS-GQD/G) hybrid nanosheets-was
      designed and synthesized for sensitive detection of hydrogen peroxide (H2O2). NS
      GQD/G was prepared through two steps. First, graphene quantum dots (GQDs) were
      self-assembled on graphene nanoplatelets via hydrothermal treatment to constitute
      hybrid nanosheets, followed by a thermal annealing procedure using the hybrid
      nanosheets and thiourea to form the NS-GQD/G hybrid nanosheets. This hybrid
      material possessed high specific surface area, numerous doping sites and edges,
      and high electrical conductivity, which leads to ultrahigh performance toward
      H2O2 electrocatalysis reduction. Under the optimal experimental conditions, the
      proposed H2O2 sensor displayed an extended linear response in the range from 0.4
      MUM to 33 mM with a low detection limit of 26 nM (S/N = 3). In addition to
      desirable selectivity, ideal reproducibility, and long-time stability, this H2O2
      sensor exhibited desirable performance in detecting H2O2 in the human serum
      samples and that released from Raw 264.7 cells. Therefore, the novel NS-GQD/G
      nanocomposite was a promising metal-free material in the fields of
      electrochemical sensing and bioanalysis.

PMID- 29023100
TI  - Surface-Enhanced Raman Scattering for Label-Free Living Single Cell Analysis.
AB  - Single cell analysis is an active research area with the hope that cellular
      process can be deciphered from a single living cell other than a cell population.
      Surface enhanced Raman scattering (SERS) has been increasingly investigated for
      single cell analysis with its ability to provide information about real-time
      dynamics of molecular processes taking place in living cells, especially upon
      external stimulation, in a contactless, noninvasive, and nondestructive way. In
      this perspective, the fundamental concepts of single cell-SERS analysis including
      origin of spectral bands and experimental parameters for spectral reproducibility
      are summarized along with the recent developments.

PMID- 29023101
TI  - Biosynthesis of Nucleoside Diphosphoramidates in Campylobacter jejuni.
AB  - Campylobacter jejuni is a pathogenic Gram-negative bacterium and a leading cause
      of food-borne gastroenteritis. C. jejuni produces a capsular polysaccharide (CPS)
      that contains a unique O-methyl phosphoramidate modification (MeOPN). Recently,
      the first step in the biosynthetic pathway for the assembly of the MeOPN
      modification to the CPS was elucidated. It was shown that the enzyme Cj1418
      catalyzes the phosphorylation of the amide nitrogen of l-glutamine to form l
      glutamine phosphate. In this investigation, the metabolic fate of l-glutamine
      phosphate was determined. The enzyme Cj1416 catalyzes the displacement of
      pyrophosphate from MgCTP by l-glutamine phosphate to form CDP-l-glutamine. The
      enzyme Cj1417 subsequently catalyzes the hydrolysis of CDP-l-glutamine to
      generate cytidine diphosphoramidate and l-glutamate. The structures of the two
      novel intermediates, CDP-l-glutamine and cytidine diphosphoramidate, were
      confirmed by 31P nuclear magnetic resonance spectroscopy and mass spectrometry.
      It is proposed that the enzyme Cj1416 be named CTP:phosphoglutamine
      cytidylyltransferase and that the enzyme Cj1417 be named gamma-glutamyl-CDP
      amidate hydrolase.

PMID- 29023102
TI  - Ubiquitin-Proteasome System Regulation of an Evolutionarily Conserved RNA
      Polymerase II-Associated Factor 1 Involved in Pancreatic Oncogenesis.
AB  - The evolutionarily conserved RNA polymerase II-associated factor 1 (Paf1) from
      yeast to humans regulates transcription and associated processes, and thus,
      malfunctions and/or misregulations of Paf1 are associated with cellular
      pathologies. Indeed, Paf1 (also known as PD2 or pancreatic differentiation 2) is
      found to be upregulated in poorly differentiated cancer cells, and such
      upregulation is involved in cellular transformation or oncogenesis. However, the
      basis for Paf1 upregulation in these cells remains largely unknown. In light of
      this, we have tested here the idea that the ubiquitin-proteasome system (UPS)
      regulates the cellular abundance of Paf1. In this direction, we analyzed the role
      of UPS in regulation of Paf1's abundance in yeast. We find that Paf1 undergoes
      ubiquitylation and is degraded by the 26S proteasome in yeast, thus deciphering
      UPS regulation of an evolutionarily conserved factor, Paf1, involved in various
      cellular processes at the crossroads of the cancer networks. Likewise, Paf1
      undergoes proteasomal degradation in well-differentiated, but not poorly
      differentiated, pancreatic cancer cells, hence pointing to the UPS in
      upregulation of Paf1 in poorly differentiated cancers. Collectively, our results
      reveal UPS regulation of Paf1 and suggest downregulation of UPS in elevating
      Paf1's abundance in poorly differentiated cancers.

PMID- 29023103
TI  - Synergistic Treatment of Mixed 1,4-Dioxane and Chlorinated Solvent Contaminations
      by Coupling Electrochemical Oxidation with Aerobic Biodegradation.
AB  - Biodegradation of the persistent groundwater contaminant 1,4-dioxane is often
      hindered by the absence of dissolved oxygen and the co-occurrence of inhibiting
      chlorinated solvents. Using flow-through electrolytic reactors equipped with
      Ti/IrO2-Ta2O5 mesh electrodes, we show that combining electrochemical oxidation
      with aerobic biodegradation produces an overadditive treatment effect for
      degrading 1,4-dioxane. In reactors bioaugmented by Pseudonocardia dioxanivorans
      CB1190 with 3.0 V applied, 1,4-dioxane was oxidized 2.5 times faster than in
      bioaugmented control reactors without an applied potential, and 12 times faster
      than by abiotic electrolysis only. Quantitative polymerase chain reaction
      analyses of CB1190 abundance, oxidation-reduction potential, and dissolved oxygen
      measurements indicated that microbial growth was promoted by anodic oxygen
      generating reactions. At a higher potential of 8.0 V, however, the cell abundance
      near the anode was diminished, likely due to unfavorable pH and/or redox
      conditions. When coupled to electrolysis, biodegradation of 1,4-dioxane was
      sustained even in the presence of the common co-contaminant trichloroethene in
      the influent. Our findings demonstrate that combining electrolytic treatment with
      aerobic biodegradation may be a promising synergistic approach for the treatment
      of mixed contaminants.

PMID- 29023104
TI  - Quantitative Evaluation of Cisplatin Uptake in Sensitive and Resistant Individual
      Cells by Single-Cell ICP-MS (SC-ICP-MS).
AB  - One of the main limitations to the Pt-therapy in cancer is the development of
      associated drug resistance that can be associated with a significant reduction of
      the intracellular platinum concentration. Thus, intracellular Pt concentration
      could be considered as a biomarker of cisplatin resistance. In this work, an
      alternative method to address intracellular Pt concentration in individual cells
      is explored to permit the evaluation of different cell models and alternative
      therapies in a relatively fast way. For this aim, total Pt analysis in single
      cells has been implemented using a total consumption nebulizer coupled to
      inductively coupled plasma mass spectrometric detection (ICP-MS). The efficiency
      of the proposed device has been evaluated in combination with flow cytometry and
      turned out to be around 25% (cells entering the ICP-MS from the cells in
      suspension). Quantitative uptake studies of a nontoxic Tb-containing compound by
      individual cells were conducted and the results compared to those obtained by
      bulk analysis of the same cells. Both sets of data were statistically comparable.
      Thus, final application of the developed methodology to the comparative uptake of
      Pt-species in cisplatin resistant and sensitive cell lines (A2780cis and A2780)
      was conducted. The results obtained revealed the potential of this analytical
      strategy to differentiate between different cell lines of different sensitivity
      to the drug which might be of high medical interest.

PMID- 29023105
TI  - Specific Detection of Carcinoembryonic Antigen Based on Fluorescence Quenching of
      Hollow Porous Gold Nanoshells with Roughened Surface.
AB  - The detection of tumor biomarkers in the early stage is highly desirable for the
      therapy of cancer. However, rapid, low-cost, sensitive, and selective detection
      of biomarkers remains a challenge owing to the sequence homology, short length,
      and low abundance. This Research Article describes the synthesis of a novel
      carcinoembryonic antigen (CEA) probe using hollow porous gold nanoparticles
      (HPGNPs) with roughened surface based on fluorescence quenching. For specific
      detection of CEA, the surface of HPGNP is modified by carboxyl modification,
      carboxyl activation, and antibody conjugation. Furthermore, to enhance the
      detection performance, we have systematically optimized the parameters, such as
      particle size, surfactants, surface roughness, surface hole size, and the
      molecule-particle distance (MPD). The results demonstrate that the fluorescence
      quenching efficiency would be enhanced with a larger particle size and surface
      hole size, roughened surface and a greater MPD. Also, with careful inspection of
      different surfactants of CTAB and PVP, we find that PVP has the optimal
      performance on fluorescence quenching. Under these optimized conditions, CEA
      could be detected with an ultralow detection limit of 1.5 pg/mL, and the probe
      shows a linear range from 2 to 100 pg/mL. The limit of detection is an order of
      intensity lower than related methods. Interference experiment results have shown
      that the influence of the interfering proteins could be neglected in the
      detection procedure.

PMID- 29023106
TI  - Noncoding RNA Surveillance: The Ends Justify the Means.
AB  - Numerous surveillance pathways sculpt eukaryotic transcriptomes by degrading
      unneeded, defective, and potentially harmful noncoding RNAs (ncRNAs). Because
      aberrant and excess ncRNAs are largely degraded by exoribonucleases, a key
      characteristic of these RNAs is an accessible, protein-free 5' or 3' end. Most
      exoribonucleases function with cofactors that recognize ncRNAs with accessible 5'
      or 3' ends and/or increase the availability of these ends. Noncoding RNA
      surveillance pathways were first described in budding yeast, and there are now
      high-resolution structures of many components of the yeast pathways and
      significant mechanistic understanding as to how they function. Studies in human
      cells are revealing the ways in which these pathways both resemble and differ
      from their yeast counterparts, and are also uncovering numerous pathways that
      lack equivalents in budding yeast. In this review, we describe both the well
      studied pathways uncovered in yeast and the new concepts that are emerging from
      studies in mammalian cells. We also discuss the ways in which surveillance
      pathways compete with chaperone proteins that transiently protect nascent ncRNA
      ends from exoribonucleases, with partner proteins that sequester these ends
      within RNPs, and with end modification pathways that protect the ends of some
      ncRNAs from nucleases.

PMID- 29023107
TI  - Luminescent Cu4I4-Cu3(Pyrazolate)3 Coordination Frameworks: Postsynthetic Ligand
      Substitution Leads to Network Displacement and Entanglement.
AB  - Six daughter complexes based on two-dimensional (2-D) luminescent Cu4I4-Cu3Pz3
      (Pz = pyrazolate) coordination networks, which exhibit an uncommon Cu4I4L3L' (L =
      pyridine; L' = acetonitrile, pyridine, pyrazine, 1,4-diazabicyclo[2.2.2]octane,
      triphenylphosphine, none) local configuration, were prepared through a
      postsynthetic modification method starting from a parent complex (L' = NH3). This
      work has successfully implemented the single-site substitution of Cu4I4-based
      coordination frameworks, which have rarely been reported for isolated Cu4I4-type
      compounds, by taking advantage of the solvent-assisted ligand substitution
      strategy recently developed in metal-organic framework (MOF) chemistry. Such a
      procedure not only resulted in the variation of local geometry in the Cu4I4 units
      but also led to interlayer network displacement and entanglement. Particularly,
      an interesting topological transformation (from 2-D to 2-D -> 3-D
      interpenetration) occurred when linear bidentate linkers (e.g., pyrazine and 1,4
      diazabicyclo[2.2.2]octane) are inserted between the 2-D layers. Moreover, the
      variation in the L' sites can effectively tune the emission colors, ranging from
      green to orange (lambdaemmax 540-605 nm at room temperature). The
      photoluminescence origins are tentatively assigned to be a mixture of 3MLCT and
      3XLCT, different from that of the well-studied isolated Cu4I4-type complexes.

PMID- 29023108
TI  - Triaryl-Boron Functionalized Dinuclear Platinum Complexes Linked by
      Photoisomerizable Bpe Ligand: Luminescence and Isomerism.
AB  - We report herein a series of triarylboron-functionalized Pt(II) dinuclear
      complexes using a photoactive bis(4-pyridyl)ethylene (bpe) bridging unit. The new
      Pt(II) complexes display phosphorescence at both room temperature and 77 K.
      Depending on the conditions under which crystals of the complexes were grown,
      either the cis- or trans-isomers could be obtained. The trans and cis isomers
      were found to undergo light-induced isomerization in solution with the trans
      isomer being the dominant species.

PMID- 29023109
TI  - Direct Evidence for Neutral N-Pyrazolyl Radicals: Paddlewheel Dibismuthanes
      Bearing Pyrazolato Ligands with Very Short Bi-Bi Single Bonds.
AB  - Neutral N-pyrazolyl radicals [3,5-R2pz]* as reactive intermediates were generated
      by one-electron oxidization of the corresponding 3,5-disubstituted pyrazolato
      anions [3,5-R2pz]- (R = tBu, Ph) with BiCl3 and trapped by the use of 5,5
      dimethyl-1-pyrroline-N-oxide as a spin trap, which was confirmed by electron
      paramagnetic resonance spectral analysis. With dimerization of the postulated
      pyrazolato low-valent BiII radical species, two novel paddlewheel
      pyrazolatodibismuthanes [L2(Bi-Bi)L2] [L = eta1,eta1-3,5-R2pz; R = tBu (5alpha,
      5beta, and 5gamma), Ph (6)] were isolated and structurally characterized.

PMID- 29023110
TI  - Cleavage of Hg-C Bonds of Organomercurials Induced by ImOHSe via Two Distinct
      Pathways.
AB  - We show that the N-methylimidazole-based selone ImOHSe having an N-CH2CH2OH
      substituent has the remarkable ability to degrade methylmercury by two distinct
      pathways. Under basic conditions, ImOHSe converts MeHgCl into biologically inert
      HgSe nanoparticles and Me2Hg via the formation of an unstable intermediate
      (MeHg)2Se (pathway I). However, under neutral conditions, in the absence of any
      base, ImOHSe facilitates the cleavage of the Hg-C bond of MeHgCl at room
      temperature (23  degrees C), leading to the formation of a stable cleaved
      product, the tetracoordinated mononuclear mercury compound (ImOHSe)2HgCl2 and
      Me2Hg (pathway II). The initial rate of Hg-C bond cleavage of MeHgCl induced by
      ImOHSe is almost 2-fold higher than the initial rate observed by ImMeSe.
      Moreover, we show that ImYSe (Y = OH, Me) has an excellent ability to dealkylate
      Me2Hg at room temperature. Under acidic conditions, in the presence of excess
      ImYSe, the volatile and toxic Me2Hg further decomposes to the tetracoordinated
      mononuclear mercury compound [(ImYSe)4Hg]2+. In addition, the treatment of ImOHSe
      with MeHgCys or MeHgSG in phosphate buffer (pH 8.5) afforded water-soluble
      Hg(SeS) nanoparticles via unusual ligand exchange reactions, whereas its
      derivative ImOMeSe or ImMeSe, lacking the N-CH2CH2OH substituent, failed to
      produce Hg(SeS) nanoparticles under identical reaction conditions.

PMID- 29023111
TI  - Catalytic Asymmetric Synthesis of Quaternary Barbituric Acids.
AB  - The catalytic asymmetric alpha-functionalization of prochiral barbituric acids, a
      subtype of pseudosymmetric 1,3-diamides, to yield the corresponding 5,5
      disubstituted (quaternary) derivatives remains essentially unsolved. In this
      study 2-alkylthio-4,6-dioxopirimidines are designed as key 1,3-diamide surrogates
      that perform exceedingly in amine-squaramide catalyzed C-C bond forming reactions
      with vinyl ketones or Morita-Baylis-Hillmann-type allyl bromides as
      electrophiles. Mild acid hydrolysis of adducts affords barbituric acid
      derivatives with an in-ring quaternary carbon in unprecedented
      enantioselectivity, offering valuable materials for biological evaluations.

PMID- 29023113
TI  - Kinetics and Mechanisms of Chemical and Biological Agents Release from
      Biopolymeric Microcapsules.
AB  - Kinetics and mechanisms of copper cations and Trichoderma viride spores release
      from uncoated and chitosan coated alginate microcapsules were investigated. The
      gelation of a fixed amount of sodium alginate at different concentrations of
      copper ion solutions resulted in distinct kinetics and release mechanisms. The
      increase in copper cation concentration promoted, but the presence of the
      chitosan layer on the microcapsule surface and the increase in microcapsule size
      reduced the rate of active agent release. Fitting to simple Korsmeyer-Peppas
      empirical model revealed that the underlying release mechanism (Fickian diffusion
      or a combination of the diffusion and erosion mechanisms) depends on the copper
      cation concentration and presence of T. viride spores. The investigation pointed
      out that the proper selection of formulation variables helps in designing
      microcapsules with the desirable release of copper ions and T. viride for plant
      protection and nutrition.

PMID- 29023112
TI  - Design of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a
      Crystallographic Surrogate Derived from Checkpoint Kinase 1 (CHK1).
AB  - Mutations in leucine-rich repeat kinase 2 (LRRK2), such as G2019S, are associated
      with an increased risk of developing Parkinson's disease. Surrogates for the
      LRRK2 kinase domain based on checkpoint kinase 1 (CHK1) mutants were designed,
      expressed in insect cells infected with baculovirus, purified, and crystallized.
      X-ray structures of the surrogates complexed with known LRRK2 inhibitors
      rationalized compound potency and selectivity. The CHK1 10-point mutant was
      preferred, following assessment of surrogate binding affinity with LRRK2
      inhibitors. Fragment hit-derived arylpyrrolo[2,3-b]pyridine LRRK2 inhibitors
      underwent structure-guided optimization using this crystallographic surrogate.
      LRRK2-pSer935 HEK293 IC50 data for 22 were consistent with binding to Ala2016 in
      LRRK2 (equivalent to Ala147 in CHK1 10-point mutant structure). Compound 22 was
      shown to be potent, moderately selective, orally available, and brain-penetrant
      in wild-type mice, and confirmation of target engagement was demonstrated, with
      LRRK2-pSer935 IC50 values for 22 in mouse brain and kidney being 1.3 and 5 nM,
      respectively.

PMID- 29023114
TI  - Exploration of Stable Strontium Phosphide-Based Electrides: Theoretical Structure
      Prediction and Experimental Validation.
AB  - Inspired by the successful synthesis of alkaline-earth-metals-based electrides
      [Ca24Al28O64]4+(e-)4 (C12A7:e-) and [Ca2N]+:e- and high-throughput database
      screening results, we explore the potential for new electrides to emerge in the
      Sr-P system through a research approach combining ab initio evolutionary
      structure searches and experimental validation. Through employing an extensive
      evolutionary structure search and first-principles calculations, we first predict
      the new structures of a series of strontium phosphides: Sr5P3, Sr8P5, Sr3P2 and
      Sr4P3. Of these structures, we identify Sr5P3 and Sr8P5 as being potential
      electrides with quasi-one-dimensional (1D) and zero-dimensional (0D) character,
      respectively. Following these theoretical results, we present the successful
      synthesis of the new compound Sr5P3 and the experimental confirmation of its
      structure. Although density functional calculations with the generalized gradient
      approximation predict Sr5P3 to be a metal, electrical conductivity measurement
      reveal semiconducting properties characterized by a distinct band gap, which
      indicates that the newly synthesized Sr5P3 is an ideal one-dimensional electride
      with the half-filled band by unpaired electrons. In addition to presenting the
      novel electride Sr5P3, we discuss the implications of its semiconducting nature
      for 1D electrides in general and propose a mechanism for the formation of
      electrides with an orbital level diagram based on first-principles calculations.

PMID- 29023115
TI  - Gallium Hydrides with a Radical-Anionic Ligand.
AB  - The reaction of Cl2GaH with a sodium salt of the dpp-Bian radical-anion (dpp
      Bian*-)Na (dpp-Bian = 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene) affords
      paramagnetic gallane (dpp-Bian*-)Ga(Cl)H (1). Oxidation of (dpp-Bian2-)Ga-Ga(dpp
      Bian2-) (2) with N2O results in the dimeric oxide (dpp-Bian*-)Ga(MU2-O)2Ga(dpp
      Bian*-) (3). A treatment of the oxide 3 with phenylsilane affords paramagnetic
      gallium hydrides (dpp-Bian*-)GaH2 (4) and (dpp-Bian*-)Ga{OSi(Ph)H2}H (5)
      depending on the reagent's stoichiometry. The reaction of digallane 2 with
      benzaldehyde produces pinacolate (dpp-Bian*-)Ga(O2C2H2Ph2) (6). In the presence
      of PhSiH3, the reaction between digallane 2 and benzaldehyde (2: PhSiH3: PhC(H)O
      = 1:4:4) affords compound 4. The newly prepared complexes 1, 3-6 consist of a
      spin-labeled diimine ligand-dpp-Bian radical-anion. The presence of the ligand
      localized unpaired electron allows the use of the ESR spectroscopy for
      characterization of the gallium hydrides reported. The molecular structures of
      compounds 1, 3-6 have been determined by the single-crystal X-ray analysis.

PMID- 29023116
TI  - Extended Concerted Rotation Technique Enhances the Sampling Efficiency of the
      Computational Peptide-Design Algorithm.
AB  - To enhance the sampling efficiency of our computational peptide-design algorithm
      in conformational space, the concerted rotation (CONROT) technique is extended to
      enable larger conformational perturbations of peptide chains. This allows us to
      make relatively large peptide conformation changes during the process of
      designing peptide sequences to bind with high affinity to a specific target.
      Searches conducted using the new algorithm identified six potential lambda N(2
      22) peptide variants, called B1-B6, which bind to boxB RNA with high affinity.
      The results of explicit-solvent atomistic molecular dynamics simulations revealed
      that four of the evolved peptides, viz. B1, B2, B3, and B5, are excellent
      candidate binders to the target boxB RNA as they have lower binding free energies
      than the original lambda N(2-22) peptide. Three of the four peptides, B2, B3, and
      B5, result from searches that contain both sequence and conformation changes,
      indicating that adding backbone motif changes to the peptide-design algorithm
      improves its performance considerably.

PMID- 29023117
TI  - Molecular Engineering of Near Infrared Absorbing Thienopyrazine Double Donor
      Double Acceptor Organic Dyes for Dye-Sensitized Solar Cells.
AB  - The thienopyrazine (TPz) building block allows for NIR photon absorption in dye
      sensitized solar cells (DSCs) when used as a pi-bridge. We synthesized and
      characterized 7 organic sensitizers employing thienopyrazine (TPz) as a pi-bridge
      in a double donor, double acceptor organic dye design. Donor groups are varied
      based on electron donating strength and sterics at the donor-pi bridge bond with
      the acceptor groups varied as either carboxylic acids or benzoic acids on the pi
      bridge. This dye design was found to be remarkably tunable with solution
      absorption onsets ranging from 750 to near 1000 nm. Interestingly, the solution
      absorption measurements do not accurately approximate the dye absorption on TiO2
      films with up to a 250 nm blue-shift of the dye absorption onset on TiO2. This
      shift in absorption and the effect on electron transfer properties is
      investigated via computational analysis, time-correlated single photon counting
      studies, and transient absorption spectroscopy. Structure-performance
      relationships were analyzed for the dyes in DSC devices with the highest
      performance observed at 17.6 mA/cm2 of photocurrent and 7.5% PCE for a
      cosensitized device with a panchromatic IPCE onset of 800 nm.

PMID- 29023118
TI  - Mixed-Penetrant Sorption in Ultrathin Films of Polymer of Intrinsic Microporosity
      PIM-1.
AB  - Mixed-penetrant sorption into ultrathin films of a superglassy polymer of
      intrinsic microporosity (PIM-1) was studied for the first time by using
      interference-enhanced in situ spectroscopic ellipsometry. PIM-1 swelling and the
      concurrent changes in its refractive index were determined in ultrathin (12-14
      nm) films exposed to pure and mixed penetrants. The penetrants included water, n
      hexane, and ethanol and were chosen on the basis of their significantly different
      penetrant-penetrant and penetrant-polymer affinities. This allowed studying
      microporous polymer responses at diverse ternary compositions and revealed
      effects such as competition for the sorption sites (for water/n-hexane or
      ethanol/n-hexane) or enhancement in sorption of typically weakly sorbing water in
      the presence of more highly sorbing ethanol. The results reveal details of the
      mutual sorption effects which often complicate comprehension of glassy polymers'
      behavior in applications such as high-performance membranes, adsorbents, or
      catalysts. Mixed-penetrant effects are typically very challenging to study
      directly, and their understanding is necessary owing to a broadly recognized
      inadequacy of simple extrapolations from measurements in a pure component
      environment.

PMID- 29023119
TI  - How Does the Central Atom Substitution Impact the Properties of a Criegee
      Intermediate? Insights from Multireference Calculations.
AB  - Complete active space self-consistent field (CASSCF) and multireference
      configuration interaction (MRCI)-based multireference calculations have been
      performed to better understand the ground state properties and the
      photodissociation mechanism of SiH2OO, a silicon analogue of the parent Criegee
      intermediate, CH2OO. The CASSCF/aug-cc-pV(T+d)Z results suggest that the ground
      state of SiH2OO is severely multireference in nature. This explains why SiH2OO
      could not be characterized in recently reported coupled cluster calculations. An
      important implication of this multireference character is the dramatically
      enhanced reactivity of SiH2OO, i.e., the calculated barrier for the cyclization
      of SiH2OO is only 4.4 kcal/mol, which is nearly 10 kcal/mol lower than that
      reported for the CH2OO case. The MRCI/aug-cc-pV(T+d)Z results on the evolution of
      the low-lying singlet electronic states along the OO bond suggest that SiH2OO
      absorbs strongly in the near UV-vis region. These results improve our fundamental
      understanding of the thermal and photobehavior of XH2OO (X = C, Si, Ge, and Sn)
      that serve as precursors for dioxiranes, an important class of oxidants for the
      synthesis of value-added chemicals, and also find their applications in
      optodevices.

PMID- 29023120
TI  - DFT Study on the Formation Mechanism of Normal and Abnormal N-Heterocyclic
      Carbene-Carbon Dioxide Adducts from the Reaction of an Imidazolium-Based Ionic
      Liquid with CO2.
AB  - To illustrate the formation mechanism of normal and abnormal N-heterocyclic
      carbene-carbon dioxide adducts (NHC-CO2 and aNHC-CO2), we implement density
      functional theory calculations on the reactions of two imidazolium-based ionic
      liquids ([C2C1Im][OAc] and [C2C1Im][CH3SO3]) with CO2. The reaction of
      [C2C1Im][OAc] with CO2 is mimicked using the gas phase model, implicit solvent
      model, and combined explicit-implicit solvent model. In the gas phase, the
      calculated barriers at 125  degrees C and 10 MPa are 12.1 kcal/mol for the
      formation of NHC-CO2 and 22.5 kcal/mol for the formation of aNHC-CO2, and the
      difference is significant (10.4 kcal/mol). However, the difference becomes less
      important (1.5 kcal/mol) as the solvation effect is considered more realistically
      using the combined explicit-implicit solvent model, rationalizing the
      experimental observation of aNHC-CO2 adduct in the [C2C1Im][OAc]-CO2 system. The
      anion of the ionic liquid is shown to play a substantial role, which can adjust
      the reactivity of imidazolium cation toward CO2: upon replacement of the basic
      [OAc]- anion with a less basic [CH3SO3]- anion, the reaction becomes very
      difficult, as indicated by high free energy barriers involved (41.4 kcal/mol for
      the formation of NHC-CO2 and 39.2 kcal/mol for the formation of aNHC-CO2). This
      is in agreement with the fact that neither NHC-CO2 or aNHC-CO2 is formed in the
      [C2C1Im][CH3SO3]-CO2 system, emphasizing the important dependence of the
      reactivity on the basicity of the anion of imidazolium-based ionic liquids for
      the formation of NHC- and aNHC-CO2 adducts.

PMID- 29023122
TI  - Water Photo-oxidation Initiated by Surface-Bound Organic Chromophores.
AB  - Organic chromophores can be synthesized by established methods and offer an
      opportunity to expand overall solar spectrum utilization for dye-sensitized
      photoelectrosynthesis cells. However, there are complications in the use of
      organic chromophores arising from the instability of their oxidized forms, the
      inability of their oxidized forms to activate a water oxidation catalyst, or the
      absence of a sufficiently reducing excited state for electron injection into
      appropriate semiconductors. Three new triarylamine donor-acceptor organic dyes
      have been investigated here for visible-light-driven water oxidation. They offer
      highly oxidizing potentials (>1 V vs NHE in aqueous solution) that are sufficient
      to drive a water oxidation catalyst and excited-state potentials (~-1.2 V vs NHE)
      sufficient to inject into TiO2. The oxidized form of one of the chromophores is
      sufficiently stable to exhibit reversible electrochemistry in aqueous solution.
      The chromophores also have favorable photophysics. Visible-light-driven oxygen
      production by an organic chromophore for up to 1 h of operation has been
      demonstrated with reasonable faradaic efficiencies for measured O2 production.
      The properties of organic chromophores necessary for successfully driving water
      oxidation in a light-driven system are explored along with strategies for
      improving device performance.

PMID- 29023121
TI  - Discovery of 3,5-Diphenyl-4-methyl-1,3-oxazolidin-2-ones as Novel, Potent, and
      Orally Available Delta-5 Desaturase (D5D) Inhibitors.
AB  - The discovery and optimization of Delta-5 desaturase (D5D) inhibitors are
      described. Investigation of the 1,3-oxazolidin-2-one scaffold was inspired by a
      pharmacophore model constructed from the common features of several hit
      compounds, resulting in the identification of 3,5-diphenyl-1,3-oxazolidin-2-one
      5h as a novel lead showing potent in vitro activity. Subsequent optimization
      focused on the modification of two metabolic sites, which provided (4S,5S)-5i, a
      derivative with improved metabolic stability. Moreover, adding a substituent into
      the upper phenyl moiety further enhanced the intrinsic activity, which led to the
      discovery of 5-[(4S,5S)-5-(4fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3
      yl]benzene-1,3-dicarbonitrile (4S,5S)-5n, endowed with excellent D5D binding
      affinity, cellular activity, and high oral bioavailability in a mouse. It
      exhibited robust in vivo hepatic arachidonic acid/dihomo-gamma-linolenic acid
      ratio reduction (a target engagement marker) in an atherosclerosis mouse model.
      Finally, an asymmetric synthetic procedure for this compound was established.

PMID- 29023123
TI  - Comparison Study on Polysaccharide Fractions from Laminaria japonica: Structural
      Characterization and Bile Acid Binding Capacity.
AB  - Our previous study has suggested that the crude polysaccharide obtained from
      Laminaria japonica by acid assisted extraction (LP-A) have significant bile acid
      binding capacity, which probably ascribed to its specific structure
      characterization. The relationship between structure characterization and bile
      acid-binding capacity of the purified LP-A fractions are still unknown. This
      paper conducted a comparison study on the structure characterization and bile
      acid-binding capacity of three LP-A fractions (LP-A4, LP-A6, and LP-A8). The
      results indicated that LP-A4, LP-A6, and LP-A8, characterized as mannoglucan,
      fucomannoglucan, and fucogalactan, had significantly different structure
      characterization. Furthermore, the bile acid-binding capacity of LP-A8 was
      obviously higher than the other fractions, which may be attributed to its highly
      branched structure, abundant sulfate, fucose, and galactose in chemical
      composition and denser interconnected macromolecule network in molecular
      morphology. This study provides scientific evidence for the potential utilization
      of LP-A8 as an attractive functional food supplement candidate for the
      hyperlipidemia population.

PMID- 29023125
TI  - Autocatalytic Oxidation of Trithionate by Iodate in a Strongly Acidic Medium.
AB  - The trithionate-iodate reaction has been studied spectrophotometrically in an
      acidic medium at 25.0 +/- 0.1  degrees C in phosphoric acid/dihydrogen phosphate
      buffer, monitoring the absorbance at 468 nm at the isosbestic point of the iodine
      triiodide ion system and at I = 0.5 M ionic strength adjusted by sodium
      perchlorate. The main characteristics of the title system are very reminiscent of
      those found recently in the pentathionate-iodate and the pentathionate-periodate
      reactions, the systems paving the way for classifying clock reactions. Thorough
      analysis revealed that the direct trithionate-iodate reaction plays a subtle role
      only to produce a trace amount of iodide ion via a finite sequence of reactions,
      and once its concentration reaches a certain level, then the reaction is almost
      exclusively governed by the trithionate-iodine and iodide-iodate reactions. The
      title reaction, as expected, was experimentally proven to be autocatalytic with
      respect to iodide ion. A simple three-step Landolt-type kinetic model is proposed
      to describe adequately the most important kinetic features of the title system
      that can easily be extended to a feasible sequence of elementary and quasi
      elementary reactions.

PMID- 29023124
TI  - Synthesis and Antimicrobial Evaluation of Fire Ant Venom Alkaloid Based 2-Methyl
      6-alkyl-Delta1,6-piperideines.
AB  - The first synthesis of 2-methyl-6-pentadecyl-Delta1,6-piperideine (1), a major
      alkaloid of the piperideine chemotype in fire ant venoms, and its analogues, 2
      methyl-6-tetradecyl-Delta1,6-piperideine (2) and 2-methyl-6-hexadecyl-Delta1,6
      piperideine (3), was achieved by a facile synthetic method starting with glutaric
      acid (4) and urea (5). Compound 1 showed in vitro antifungal activity against
      Cryptococcus neoformans and Candida albicans with IC50 values of 6.6 and 12.4
      MUg/mL, respectively, and antibacterial activity against vancomycin-resistant
      Enterococcus faecium with an IC50 value of 19.4 MUg/mL, while compounds 2 and 3
      were less active against these pathogens. All three compounds strongly inhibited
      the parasites Leishmania donovani promastigotes and Trypanosoma brucei with IC50
      values in the range of 5.0-6.7 and 2.7-4.0 MUg/mL, respectively.

PMID- 29023126
TI  - Lyotropic Liquid-Crystalline Nanosystems as Drug Delivery Agents for 5
      Fluorouracil: Structure and Cytotoxicity.
AB  - Lyotropic cubic liquid-crystalline systems have received increasing attention due
      to their unique microstructural and physicochemical properties as efficient
      nanocarriers for drug delivery. We report the preparation and characterization of
      bulk phases and cubosome dispersions of phytantriol loaded with the anticancer
      drug 5-fluorouracil, in neutral and anionic forms. In both cases, a Pn3m cubic
      phase was observed. The phytantriol phase behavior can be influenced by the
      addition of ionic agents, and, to this purpose, a positively charged lipid, such
      as N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride salt (DOTAP),
      was included in the studied formulations. It was found to induce a variation of
      the spontaneous membrane curvature of the phytantriol lipid bilayer, generating a
      transition from the Pn3m to the Im3m cubic phase. When 5-fluorouracil, in its
      anionic form (5-FUs), was encapsulated in these latter systems, a further
      transition to the HII hexagonal phase was observed as a consequence of the
      formation of a complex phytantriol/DOTAP/5-FUs. The physicochemical
      characterization was performed with various complementary techniques including
      synchrotron small-angle X-ray scattering, dynamic light scattering, and
      attenuated total reflection Fourier transform infrared and UV resonance Raman
      spectroscopies. Encapsulation of 5-fluorouracil in the corresponding
      nanodispersions was evaluated, and their in vitro cytotoxicity was assessed in
      MDA-MB-231 cell line. Phytantriol cubosomes containing 5-fluorouracil showed a
      higher toxicity compared with the bare drug solution, and hence they represent
      potential nanocarriers in the delivery of 5-fluorouracil for cancer therapy.

PMID- 29023127
TI  - Surface-Mediated DNA Hybridization: Effects of DNA Conformation, Surface
      Chemistry, and Electrostatics.
AB  - Single-molecule Forster Resonance Energy Transfer (FRET) was used to study the
      dynamic association of mobile donor-labeled ssDNA oligonucleotides ("target")
      with covalently immobilized complementary acceptor-labeled ssDNA oligonucleotides
      ("probe"). While probe-target association events were resolved for all
      experiments, such FRET events were far more likely to occur in systems with
      complementarity and on hydrophobic, as compared to hydrophilic, surfaces. The
      distribution of donor-acceptor association-time intervals did not exhibit simple
      first-order kinetics, and when decomposed into a superposition of first-order
      processes, only a small fraction of events corresponded to a long-lived state
      that was presumed to represent true DNA hybridization, while the majority of
      association events were transient, representing nonspecific associations or
      partial hybridization. The structure of the DNA target and probe affected both
      the stability of the hybridized state, as well as the likelihood that an
      association between the two led to hybridization. In particular, the likelihood
      of hybridization decreased for longer target strands and for targets with stem
      loop secondary structure. The presence of oligonucleotide secondary structure
      reduced the stability of hybridization, while greater complementarity increased
      stability of the hybridized state. Interestingly, increased ionic strength (i.e.,
      greater electrostatic screening) increased the probability of hybridization but
      did not influence the lifetime of the hybridized state. Combined, these
      observations provide a nuanced view of surface-mediated DNA hybridization, where
      various factors independently influence the probability and stability of
      hybridization.

PMID- 29023128
TI  - Mapping Solvation Environments in Porous Metal-Organic Frameworks with Infrared
      Chemical Imaging.
AB  - We report here the first mesoscale characterization of solvent environments in
      the metal-organic framework (MOF) Cu3(BTC)2 using infrared imaging. Two
      characteristic populations of the MOF structures corresponding to the carboxylate
      binding to the Cu(II) (metal) ions were observed, which reflect a regular
      solvated MOF structure with axial solvents in the binuclear copper paddlewheel
      and an unsolvated defect mode that lacks axial solvent coordination. Infrared
      imaging also shows strong correlation between solvent localization and the
      spatial distribution of the solvated population within the MOF. This is a vital
      result as any remnant solvent molecules adsorbed inside of MOFs can render them
      less effective. We propose fast IR imaging as a potential characterization
      technique that can measure adsorbate and defect distributions in MOFs.

PMID- 29023129
TI  - Robust and Selective Switching of an FeIII Spin-Crossover Compound on
      Cu2N/Cu(100) with Memristance Behavior.
AB  - The switching between two spin states makes spin-crossover molecules on surfaces
      very attractive for potential applications in molecular spintronics. Using
      scanning tunneling microscopy, the successful deposition of [Fe(pap)2]+ (pap = N
      2-pyridylmethylidene-2-hydroxyphenylaminato) molecules on Cu2N/Cu(100) surface is
      evidenced. The deposited FeIII spin-crossover compound is controllably switched
      between three different states, each of them exhibiting a characteristic
      tunneling conductance. The conductance is therefore employed to readily read the
      state of the molecules. A comparison of the experimental data with the results of
      density functional theory calculations reveals that all Fe(pap)2 molecules are
      initially in their high-spin state. The two other states are compatible with the
      low-spin state of the molecule but differ with respect to their coupling to the
      substrate. As a proof of concept, the reversible and selective nature of the
      switching is used to build a two-molecule memory.

PMID- 29023130
TI  - Neutron Reflectometry Elucidates Protein Adsorption from Human Blood Serum onto
      PEG Brushes.
AB  - Poly(ethylene glycol) (PEG) brushes are reputed for their ability to prevent
      undesired protein adsorption to material surfaces exposed to biological fluids.
      Here, protein adsorption out of human blood serum onto PEG brushes anchored to
      solid-supported lipid monolayers was characterized by neutron reflectometry,
      yielding volume fraction profiles of lipid headgroups, PEG, and adsorbed proteins
      at subnanometer resolution. For both PEGylated and non-PEGylated lipid surfaces,
      serum proteins adsorb as a thin layer of approximately 10 A, overlapping with the
      headgroup region. This layer corresponds to primary adsorption at the grafting
      surface and resists rinsing. A second diffuse protein layer overlaps with the
      periphery of the PEG brush and is attributed to ternary adsorption due to protein
      PEG attraction. This second layer disappears upon rinsing, thus providing a first
      observation of the structural effect of rinsing on protein adsorption to PEG
      brushes.

PMID- 29023131
TI  - Direct Synthesis of Acyl Fluorides from Carboxylic Acids with the Bench-Stable
      Solid Reagent (Me4N)SCF3.
AB  - A convenient, highly efficient, and selective transformation of aliphatic and
      aromatic carboxylic acids to acyl fluorides is reported. In contrast to
      established approaches that require toxic or volatile additives and base and
      reaction control (i.e., cooling, slow addition), this protocol allows for a
      straightforward access to various R-COF entities upon direct reaction with the
      bench-stable, solid reagent (Me4N)SCF3 at room temperature. The method is base-
      and additive-free, compatible with late-stage synthetic applications, high
      functional group tolerance, and facile target compound purification via
      filtration.

PMID- 29023132
TI  - Zampanolide Binding to Tubulin Indicates Cross-Talk of Taxane Site with
      Colchicine and Nucleotide Sites.
AB  - The marine natural product zampanolide and analogues thereof constitute a new
      chemotype of taxoid site microtubule-stabilizing agents with a covalent mechanism
      of action. Zampanolide-ligated tubulin has the switch-activation loop (M-loop) in
      the assembly prone form and, thus, represents an assembly activated state of the
      protein. In this study, we have characterized the biochemical properties of the
      covalently modified, activated tubulin dimer, and we have determined the effect
      of zampanolide on tubulin association and the binding of tubulin ligands at other
      binding sites. Tubulin activation by zampanolide does not affect its longitudinal
      oligomerization but does alter its lateral association properties. The covalent
      binding of zampanolide to beta-tubulin affects both the colchicine site, causing
      a change of the quantum yield of the bound ligand, and the exchangeable
      nucleotide binding site, reducing the affinity for the nucleotide. While these
      global effects do not change the binding affinity of 2-methoxy-5-(2,3,4
      trimethoxyphenyl)-2,4,6-cycloheptatrien-1-one (MTC) (a reversible binder of the
      colchicine site), the binding affinity of a fluorescent analogue of GTP (Mant
      GTP) at the nucleotide E-site is reduced from 12 +/- 2 * 105 M-1 in the case of
      unmodified tubulin to 1.4 +/- 0.3 * 105 M-1 in the case of the zampanolide
      tubulin adduct, indicating signal transmission between the taxane site and the
      colchicine and nucleotide sites of beta-tubulin.

PMID- 29023133
TI  - Women's Experiences of Food Insecurity and Coping Strategies in the Chittagong
      Hill Tracts, Bangladesh.
AB  - Despite advances in food production and distribution technologies, global food
      insecurity continues throughout parts of South Asia. Using ethnographic data
      collected from the Chittagong Hill Tracts (CHT) in Bangladesh, this article
      reports on gendered and ethnocultural variations in experiences of food
      insecurity. Three key findings are that (1) regardless of ethnicity, the majority
      of the households in this study suffered moderate food insecurity; (2) food
      insecurity was higher among female-headed households; and (3) women's means of
      coping strategies varied depending on household structure and ethnic identity. It
      is argued that indigenous women's coping strategies were protective in comparison
      with Bengali women's experiences.

PMID- 29023134
TI  - A systematic review of correlates of depression among older Chinese and Korean
      immigrants: what we know and do not know.
AB  - OBJECTIVES: Guided by the stress and coping theory, this study provides a
      systematic review of existing research on acculutration, family support, and
      social support related correlates of depression among older Chinese and Korean
      immigrants in the United States. METHOD: A comprehensive literature search was
      conducted in CINAHL Plus, Abstracts in Social Gerontology, AgeLine, Social Work
      Abstracts, PubMed, PsychINFO, and Social Science Citation Index databases to
      identify relevant articles that presented multivariate analysis results. RESULTS:
      A total of 55 articles were identified, with the vast majority focusing on older
      Korean immigrants. The overall evidence showed that length of residence was
      largely unrelated to depression, and poor Enligsh proficiency also had a weak
      correlation with depression. However, a low level of acculturation measured by
      multidimensional scales was consistently associated with more depressive
      symptoms. Overall, living arrangements and the size and frequency of contact of
      both kin and non-kin networks were weak correlates of depression. In contrast,
      negative family and social interactions seem to be more consequential for
      depression in the two groups than positive relations and support. CONCLUSION: The
      findings show that established acculturation instruments are useful tools to
      identify at-risk older Chinese and Korean immigrants. Future studies need to
      further examine which aspects of acculturation experience are more influential
      for immigrants' mental health. Although often conceptualized as important coping
      resources, family and social networks could present significant stressors for
      older immigrants. Future research and services could focus on these contexts to
      improve the mental health of these two rapidly increasing Asian populations.

PMID- 29023135
TI  - Dietary Patterns and Dietary Adequacy of Street Children in Dhaka, Bangladesh.
AB  - The negative impact of poverty on the biological well-being of children is well
      established. The purpose of the present study was to evaluate the impact of the
      stress of full-time street life on the dietary patterns and dietary adequacy of
      street children living in Dhaka, Bangladesh. This was accomplished by comparing
      the nutritional patterns of full-time street children with those of other poor
      children in Dhaka who also spend their days on the streets but who return to
      their families at night. There were few differences between groups, possibly due
      to street children being a select group. However, there were significant sex
      differences in both groups of children, with boys tending to have more diverse
      and more adequate diets than girls. The cause of this latter pattern could not be
      determined with the available data but may involve cultural values favoring males
      over females.

PMID- 29023136
TI  - Nutrition Education Intervention to Improve Nutrition-Related Knowledge,
      Attitudes, and Behaviors for Hispanic Children.
AB  - This study was performed to assess the effect of a nutrition education
      intervention on the nutrition-related knowledge, attitudes, and behaviors of
      Hispanic children, ages 6-10 years, in a local after-school program. The
      intervention included seven weekly lessons that lasted an average of 30 minutes
      each. Pre- and post-tests were used to evaluate the program. There was a
      statistically significant difference, p < .04, observed for the intervention
      group (n = 7) between the pre- and posttest scores for knowledge. In addition,
      the posttest scores for the intervention group were significantly higher, p <
      .04, than for the control group (n = 3). Changes in nutrition-related attitudes
      and behavior were not significant. The only measure that showed significant
      improvement was knowledge about the differences between healthy and unhealthy
      food choices after the intervention, which is crucial in the development of
      healthy behaviors.

PMID- 29023138
TI  - Measurement of expressive vocabulary in school-age children: Development and
      application of the Kilifi Naming Test (KNT).
AB  - The dearth of locally developed measures of language makes it difficult to detect
      language and communication problems among school-age children in sub-Saharan
      African settings. We sought to describe variability in vocabulary acquisition as
      an important element of global cognitive functioning. Our primary aims were to
      establish the psychometric properties of an expressive vocabulary measure,
      examine sources of variability, and investigate the measure's associations with
      non-verbal reasoning and educational achievement. The study included 308 boys and
      girls living in a predominantly rural district in Kenya. The developed measure,
      the Kilifi Naming Test (KNT), had excellent reliability and acceptable convergent
      validity. However, concurrent validity was not adequately demonstrated. In the
      final regression model, significant effects of schooling and area of residence
      were recorded. Contextual factors should be taken into account in the
      interpretation of test scores. There is need for future studies to explore the
      concurrent validity of the KNT further.

PMID- 29023137
TI  - Sexual vs. Nonsexual Currently Most Upsetting Trauma: A Fresh Look at Attenuation
      of Sexual Response, Alcohol Intoxication, and Post-Traumatic Stress.
AB  - This study examined the dependence of sexual response (vaginal pulse amplitude
      [VPA] and subjective sexual arousal) on alcohol intoxication (.10% breath alcohol
      concentration [BrAC] versus no alcohol) and the nature of a woman's currently
      most upsetting traumatic event (C-MUTE), whether it was sexual (e.g., rape) or
      nonsexual (e.g., combat). Self-reported sexual outcomes were also compared by C
      MUTE type. A total of 117 women completed background measures and either drank
      alcoholic or nonalcoholic beverages. They were shown erotic films and their VPA
      was assessed. A two (sexual versus nonsexual C-MUTE) by two (.10% BrAC versus no
      alcohol) analysis of variance (ANOVA) showed that, controlling for post-traumatic
      stress (PTS) symptoms, women with a sexual C-MUTE showed lower percent VPA change
      than women with a nonsexual C-MUTE. No significant effects were found for
      subjective sexual arousal. A multivariate analysis of variance (MANOVA) showed
      that women with a sexual C-MUTE reported more frequent anxiety and inhibition
      during partnered sex and more frequent lack of vaginal lubrication versus women
      with a nonsexual C-MUTE. There was no significant interaction between C-MUTE and
      alcohol intoxication. Whether a woman is currently upset by past sexual
      victimization may influence current sexual difficulties. Attenuated VPA may be
      attributable to the sexual nature of a C-MUTE as opposed to general trauma
      exposure.

PMID- 29023139
TI  - Sheltering Haitian Humanitarian Parolees in San Diego: A Local Health
      Department's Response to an International Crisis.
AB  - From the Field is a semi-regular column that explores what it means to be a local
      health professional on the front lines of an emergency. National Association of
      County and City Health Officials (NACCHO) members share their stories of
      preparing for and responding to disasters, epidemics, and other major health
      issues. Through exploring the analysis of the challenges faced and the solutions
      developed, readers can learn how these public health champions keep their
      communities safe even in extreme situations. Readers may submit topics of
      interest to the column's editor, Meghan McGinty, PhD, MPH, MBA, at
      mmcginty@naccho.org .

PMID- 29023140
TI  - Genetic Polymorphisms of Cytochrome P450 Enzymes and Transport Proteins in a
      Russian Population and Three Ethnic Groups of Dagestan.
AB  - AIM: The objective of this study was to investigate the prevalence of polymorphic
      markers of the CYP2C19, CYP2C9, CYP2D6, SLCO1B1, and ABCB1 genes among the three
      ethnic groups in Dagestan and compare it with the carrier frequency of these
      markers among the Russian population living in Moscow. METHODS: The study
      involved 186 healthy, unrelated, and chronic medication-free volunteers (53 males
      and 133 females) of the three ethnic groups in the Dagestan Republic: 46 Laks, 90
      Avars, and 50 Dargins. Genotyping was performed using real-time polymerase chain
      reaction-based methods. The allelic prevalences of the three Dagestan peoples
      were compared with ethnic Russians from the Moscow region. RESULTS: Statistically
      significant differences for the following gene polymorphisms: CYP2C19*17,
      CYP2C9*3, ABCB1 (C3435T), SLCO1B1*5 were found between the Russian population and
      the three ethnic groups of the Dagestan republic. CONCLUSION: The data obtained
      from this study will help with prioritization genotyping in the region.

PMID- 29023141
TI  - Sexual Identity Disclosure and Awareness of HIV Prevention Methods Among Black
      Men Who Have Sex With Men.
AB  - Black men who have sex with men (BMSM) are disproportionately affected by the
      human immunodeficiency virus (HIV) epidemic, yet we know little about how HIV
      negative BMSM of different sexual orientations access HIV prevention strategies.
      Identity development, minority stress, and disclosure theories suggest that for
      people of different sexual orientations, disclosure of sexual identity may be
      related to health behaviors. We performed a latent class analysis on a sample of
      650 BMSM (Mage = 33.78, SD = 11.44) from Atlanta, Georgia, to explore whether
      sexual orientation, disclosure of sexual identity, and relationship status were
      related to HIV prevention strategies, including awareness of PrEP (pre-exposure
      prophylaxis) and PEP (post-exposure prophylaxis) and frequency of HIV testing. We
      found three distinct BMSM classes referred to as (1) closeted bisexuals, (2)
      sexual identity managers, and (3) gay, out, and open; all classes primarily
      engaged in casual sex. Classes differed in their awareness and access to HIV
      prevention strategies. The closeted bisexual class was least aware of and least
      likely to access HIV prevention. Findings have important implications for future
      research, namely the consideration of sexual identity and disclosure among BMSM.
      With this knowledge, we may be able to engage BMSM in HIV/sexually transmitted
      infection (STI) prevention services.

PMID- 29023142
TI  - Diffusion-weighted imaging in ectopic pregnancy: ring of restriction sign.
AB  - OBJECTIVE: To demonstrate the diffusion-weighted imaging (DWI) findings of
      ectopic pregnancy (EP) and introduce the "ring of restriction" sign by discussing
      possible causes. METHODS: Between January 2014 and January 2017, patients with EP
      and examined by MRI on a 3T scanner were retrospectively evaluated. MRI and DWI
      findings were recorded. RESULTS: A total of 40 patients were diagnosed with EP at
      our university hospital, 8 of whom (20%) were evaluated by MRI and DWI. All of
      them were haemodynamically and clinically stable and could be imaged adequately.
      Locations were ovary (n = 3, 37.5%), tuba (n = 2, 25%), Caesarean section scar (n
      = 2, 25%) and parauterine (n = 1, 12.5%). In all eight EPs, the gestational sac
      diameter was compatible with 7-9 weeks. With DWI, the gestational sac was seen as
      a thick-walled cyst-like structure. The thick wall showed diffusion restrictions
      in all patients (ring of restriction sign). CONCLUSIONS: DWI through its cellular
      and molecular evidence may contribute diagnosis of EP. Advances in knowledge:
      Being aware of the EP wall shows diffusion restriction (ring of restriction)
      avoids interpretation errors especially in appropriate clinical setting with no
      need for contrast material.

PMID- 29023143
TI  - Changes of Emphysema Parameters over the Respiratory Cycle During Free Breathing:
      Preliminary Results Using Respiratory Gated 4D-CT.
AB  - The purpose of this research was to evaluate respiratory gated CT of the lung in
      patients with COPD for analysis of parenchymal characteristics who were potential
      candidates for volume reduction surgery. Eleven patients with clinically known
      emphysematous disease underwent a respiratory gated, free-breathing 64-multislice
      CT (Aquilion 64, Toshiba). Retrospective image reconstruction was performed
      similar to cardiac CT at every 10% of the respiratory loop, resulting in 10
      complete volumetric datasets at 10 equidistant time points. All images were
      transferred onto a PC for calculation of the total lung volume, emphysema volume,
      emphysema index, and mean lung density. Complete datasets could be successfully
      reconstructed in all patients. The mean lung volume increased from 6.9 L to 7.5 L
      over the respiratory cycle. Emphysema volume increased from 1.6 L to 2.0 L and
      emphysema index from 22.6% to 26.5% from expiration to inspiration. In
      conclusion, respiratory gated chest 4D-CT allows for combined morphologic and
      functional image analysis, which can provide new insight into functional
      impairment and individual treatment planning.

PMID- 29023144
TI  - Birth Cohort Differences in Sexual Identity Development Milestones Among HIV
      Negative Gay and Bisexual Men in the United States.
AB  - The coming-out process for gay and bisexual men (GBM) involves crossing sexual
      identity development (SID) milestones: (1) self-awareness of sexual attraction to
      the same sex, (2) self-acceptance of an identity as gay or bisexual, (3)
      disclosure of this sexual identity to others, and (4) having sex with someone of
      the same sex. We examined trends in SID milestones by birth cohort in a 2015 U.S.
      national sample of GBM (n = 1,023). Birth cohort was independent of when men
      first felt sexually attracted to someone of the same sex (median age 11 to 12).
      However, with the exception of age of first same-sex attraction, older cohorts
      tended to pass other milestones at later ages than younger cohorts. Latent class
      analysis (LCA) of SID milestone patterns identified three subgroups. The majority
      (84%) began sexual identity development with same-sex attraction around the onset
      of puberty (i.e., around age 10) and progressed to self-identification, same-sex
      sexual activity, and coming out-in that order. The other two classes felt same
      sex attraction during teen years (ages 12.5 to 18.0) but achieved the remaining
      SID milestones later in life. For 13% of men, this was during early adulthood;
      for 3% of men, this was in middle adulthood. Findings highlight the need to
      monitor ongoing generational differences in passing SID milestones.

PMID- 29023146
TI  - Is there a role for combined use of gabapentin and pregabalin in pain control?
      Too good to be true?
AB  - Gabapentin (Neurontin 1 ) and pregabalin (Lyrica 2 ) are first- and second
      generation alpha2delta ligands, respectively, and are both approved for use as
      adjunctive therapy in pain control. Although they do not bind to gamma
      aminobutyric acid (GABA) receptors they have been successfully used to treat
      neuropathic pain conditions. Their mechanism of action is not yet fully
      understood, but research has demonstrated promising results. Despite their
      similarities, they have been used in combination in both clinical and research
      situations, and have been noted to have a synergistic effect in pain control
      without concern for clinically significant pharmacokinetic interactions. This
      combined approach can be made use of to reduce the dose of an individual agent,
      its side effects, and to enhance therapeutic response compared to a single agent.
      Pharmacokinetics, drug interactions, and adverse reaction to combinations have to
      be taken into consideration before combination therapy with gabapentin and
      pregabalin is proposed as first-line treatment in refractory pain situations and
      in patients with low levels of tolerance for an individual agent.

PMID- 29023145
TI  - Mechanical properties and drug release of venlafaxine HCl solid mini matrices
      prepared by hot-melt extrusion and hot or ambient compression.
AB  - : Objective/significance: To elucidate the role of plasticizers in different mini
      matrices and correlate mechanical properties with drug release. METHODS:
      Cylindrical pellets were prepared by hot-melt extrusion (HME) and mini tablets by
      hot (HC) and ambient compression (AC). Venlafaxine HCl was the model drug,
      Eudragit(r) RSPO the matrix former and citric acid or Lutrol(r) F127 the
      plasticizers. The matrices were characterized for morphology, crystallinity, and
      mechanical properties. The influence of plasticizer's type and content on the
      extrusion pressure (Pe) during HME and ejection during tableting was examined and
      the mechanical properties were correlated with drug release parameters. RESULTS:
      Resistance to extrusion and tablet ejection force were reduced by Lutrol(r) F127
      which also produced softer and weaker pellets with faster release, but harder and
      stronger HC tablets with slower release. HME pellets showed greater tensile
      strength (T) and 100 times slower release than tablets. Pe correlated with T and
      resistance to deformation of the corresponding pellets (r2 = 0.963 and 0.945).
      For both HME and HC matrices the decrease of drug release with T followed a
      single straight line (r2 = 0.990) and for HME the diffusion coefficient (De) and
      retreat rate constant (kb) decreased linearly with T (r2 = 0.934 and 0.972).
      CONCLUSIONS: Lutrol(r) F127 and citric acid are efficient plasticizers and
      Lutrol(r) F127 is a thermal binder/lubricant in HC compression. The different
      bonding mechanisms of the matrices were reflected in the mechanical strength and
      drug release. Relationships established between T and drug release parameters for
      HME and HC matrices may be useful during formulation work.

PMID- 29023147
TI  - Nitrogen Oxides in Early Earth's Atmosphere as Electron Acceptors for Life's
      Emergence.
AB  - We quantify the amount of nitrogen oxides (NOx) produced through lightning and
      photochemical processes in the Hadean atmosphere to be available in the Hadean
      ocean for the emergence of life. Atmospherically generated nitrate (NO3-) and
      nitrite (NO2-) are the most attractive high-potential electron acceptors for
      pulling and enabling crucial redox reactions of autotrophic metabolic pathways at
      submarine alkaline hydrothermal vents. The Hadean atmosphere, dominated by CO2
      and N2, will produce nitric oxide (NO) when shocked by lightning. Photochemical
      reactions involving NO and H2O vapor will then produce acids such as HNO, HNO2,
      HNO3, and HO2NO2 that rain into the ocean. There, they dissociate into or react
      to form nitrate and nitrite. We present new calculations based on a novel
      combination of early-Earth global climate model and photochemical modeling, and
      we predict the flux of NOx to the Hadean ocean. In our 0.1-, 1-, and 10-bar pCO2
      models, we calculate the NOx delivery to be 2.4 * 105, 6.5 * 108, and 1.9 * 108
      molecules cm-2 s-1. After only tens of thousands to tens of millions of years,
      these NOx fluxes are expected to produce sufficient (micromolar) ocean
      concentrations of high-potential electron acceptors for the emergence of life.
      Key Words: Nitrogen oxides-Nitrate-Nitrite-Photochemistry-Lightning-Emergence of
      life. Astrobiology 17, 975-983.

PMID- 29023148
TI  - Nonstandardized Terminology to Describe Focal Liver Lesions in Patients at Risk
      for Hepatocellular Carcinoma: Implications Regarding Clinical Communication.
AB  - OBJECTIVE: The purpose of this study is to determine the correlation between
      malignancy risk of focal liver observations in patients at risk for
      hepatocellular carcinoma (HCC) implied by phrases used in nonstructured radiology
      reports with the risk inferred by hepatologists. MATERIALS AND METHODS: We
      performed a retrospective review of nonstructured radiology reports issued before
      Liver Imaging and Reporting Data System (LI-RADS) adoption from four-phase liver
      CT examinations of patients at risk for HCC. The phrase used by the radiologist
      in the report impression to describe each focal liver observation was recorded.
      Five hepatologists independently inferred the LI-RADS category from each phrase.
      Two abdominal radiologists independently reviewed the images and, blinded to all
      other information, assigned a LI-RADS category to each observation. Discrepancies
      were resolved by consensus. RESULTS: One hundred five observations in 77 patients
      were reported by 23 radiologists using 29 phrases. The most common phrase,
      "consistent with HCC" (n = 20), was applied to radiologist-assigned LR-3 (n = 1),
      LR-4 (n = 5), LR-5 (n = 11), and LR-5V (n = 3) observations. Eleven phrases were
      used more than once. Sixteen phrases were associated with LR-4 or higher
      observations; among these, hepatologists misinterpreted 37% of LR-4 or lower
      observations as definitely HCC and 46% of LR-5 and LR-5V observations as not
      definitely HCC. Overall, there was modest correlation (r = 0.69) between
      radiologist-assigned and hepatologist-inferred categories. CONCLUSION:
      Nonstandardized terminology results in inaccurate communication of HCC risk.
      Structured reporting systems such as LI-RADS may improve communication by
      conveying unambiguous estimates of malignancy risk.

PMID- 29023149
TI  - Benign Posttraumatic Pseudopneumoperitoneum.
AB  - OBJECTIVE: The objective of our study was to retrospectively determine the
      anatomic distribution of chest wall ectopic gas resembling pneumoperitoneum
      (i.e., pseudopneumoperitoneum) and its relationship with trauma mechanisms and
      clinical outcomes using CT. MATERIALS AND METHODS: Investigators from two
      separate trauma referral centers screened 492 chest, abdomen, and pelvis CT
      examinations of patients who had sustained any form of trauma between 2010 and
      2015. After excluding 186 patients with recognized causes of ectopic gas, 306
      patients (211 men and 95 women; mean age, 44.5 years; range, 6-95 years) remained
      for analysis by two radiology residents in center 1 and a radiology resident in
      center 2. Positive cases were reviewed by all investigators, including an
      experienced fellowship-trained abdominal radiologist. The anatomic location of
      the pseudopneumoperitoneum, injury severity score, trauma velocity (high speed vs
      low or unknown speed), trauma mechanism, clinical findings on follow-up, and
      exploratory laparotomy data were collected for patients with
      pseudopneumoperitoneum. Two hundred consecutive nontrauma CT examinations from
      2015 were selected as control cases by a resident in center 1. The t test and chi
      square test were used for determining associations. RESULTS:
      Pseudopneumoperitoneum was identified in 5.2% of patients, occurring bilaterally
      adjacent to the lower six costochondral junctions, and was significantly more
      common with high-velocity trauma than with low-velocity trauma (p = 0.010). None
      of the patients with pseudopneumoperitoneum had evidence of perforated hollow
      viscus at surgery (n = 2) or on clinical follow-up (n = 14). No patients had
      unnecessary surgery due to pseudopneumoperitoneum. CONCLUSION:
      Pseudopneumoperitoneum is a posttraumatic phenomenon centered near the lower six
      costochondral junctions. Recognizing these findings may help prevent unnecessary
      laparotomy in the trauma setting.

PMID- 29023150
TI  - Incisional Hernia Repair: What the Radiologist Needs to Know.
AB  - OBJECTIVE: Incisional hernias are becoming more prevalent with increases in the
      obesity of the population and the complexity of abdominal surgeries.
      Radiologists' understanding of these hernias is limited. This article examines
      abdominal wall anatomy, surgical techniques, the role of imaging (current and
      emerging), and complications from the surgical perspective, to enhance to the
      role of the radiologist. CONCLUSION: Knowledge of the relevant anatomy, surgical
      techniques, and postoperative complications in patients with incisional hernial
      repair can help the radiologist improve care.

PMID- 29023152
TI  - Primary Hepatic Neoplasms of Vascular Origin: Key Imaging Features and
      Differential Diagnoses With Radiology-Pathology Correlation.
AB  - OBJECTIVE: This article describes, illustrates, and correlates imaging and
      pathologic features of primary vascular mesenchymal neoplasms of the liver, which
      arise from the vascular endothelium and perivascular epithelioid cells.
      CONCLUSION: Familiarity with the spectrum of benign, malignant-potential and
      malignant vascular neoplasms, and nonneoplastic mimickers allows consideration in
      the differential diagnosis of enhancing hepatic masses. Understanding relevant
      pathologic features facilitates recognition of key imaging features, specifically
      dynamic contrast enhancement patterns on CT and MRI, which provide a useful
      classification system.

PMID- 29023151
TI  - Interpretive Differences Between Patients and Radiologists Regarding the
      Diagnostic Confidence Associated With Commonly Used Phrases in the Radiology
      Report.
AB  - OBJECTIVE: Despite patients' increasing interest in reading their own imaging
      results, little is known about how patients interpret the reporting terminology
      of radiologists. The purpose of this study was to survey patients and
      radiologists to improve understanding of how each group views commonly used
      phrases within the radiology report. SUBJECTS AND METHODS: Patients and
      radiologists were asked to assign a numerical likelihood of the presence of
      metastatic disease based on their understanding of radiology report phrasing.
      Commonly used qualifying phrases, such as "likely represents," "concerning for,"
      and "cannot exclude" were evaluated to compare differences in interpretation
      between patients and radiologists. Potential responses for statistical
      likelihoods included 0-25%, 26-50%, 51-75%, 76-99%, and 100%. RESULTS: There was
      a significant difference between the two groups with respect to assigned
      statistical likelihoods for most phrases. Patients identified the phrase
      "probably meta-static disease" as conferring the highest likelihood of true
      malignancy, even though radiologists rated this phrase as conferring the sixth
      highest likelihood (p = 0.002). Radiologists consistently identified the phrase
      "diagnostic for metastatic disease" as conveying the highest likelihood of
      metastatic disease, whereas patients ranked this phrase as having the third
      highest numerical likelihood (p < 0.001). The phrase "cannot exclude cancer" was
      assigned the lowest numerical likelihood by both groups. CONCLUSION: Patients and
      radiologists have differing perceptions of the specific semantic meaning of the
      language in radiology reports. A variable interpretation of the radiologist's
      diagnostic confidence may lead to confusion and dissatisfaction with the report.
      Radiologists should consider that patients read their reports and should endeavor
      to use strategies to convey imaging results clearly and effectively.

PMID- 29023153
TI  - Predictability of 99mTc-Galactosyl Human Serum Albumin Scintigraphy for
      Posthepatectomy Liver Failure.
AB  - OBJECTIVE: Posthepatectomy liver failure (PHLF) is one of the most serious
      complications after hepatectomy. The objective of the present study is to assess
      the potential diagnostic ability of 99mTc-galactosyl human serum albumin (GSA)
      scintigraphy to predict PHLF as defined by the International Study Group of Liver
      Surgery (ISGLS). MATERIALS AND METHODS: Data from 100 patients who underwent
      99mTc-GSA scintigraphy and subsequent hepatectomy were retrospectively analyzed.
      The blood clearance ratio (HH15), hepatic uptake ratio (LHL15), and maximal
      removal rate (Rmax) of 99mTc-GSA (GSA-Rmax) were calculated as scintigraphic
      parameters for the total liver. In addition to the ratio of preoperatively
      estimated remnant liver (ERL) counts to total liver counts (rERL-GSA), the ratio
      of actual remnant liver (ARL) counts to total liver counts (rARL-GSA), determined
      by applying a more accurate resection line with reference to both pre- and
      postoperative CT, was obtained from SPECT images. Functional remnant liver
      parameters of ERL-LHL15 (LHL15 of the estimated remnant liver), ERL-Rmax (maximal
      removal rate of estimated remnant liver counts), ARL-LHL15 (LHL15 of the actual
      remnant liver), and ARL-Rmax (maximal removal rate of actual remnant liver
      counts) were calculated using these values. ROC analysis was performed to
      evaluate the ability of these parameters to predict PHLF. Multivariate analysis
      was performed to identify independent predictors of PHLF. RESULTS: PHLF occurred
      in 33 patients. Each of the ARL parameters had a significantly higher diagnostic
      performance compared with the corresponding ERL parameter (AUC values: for rARL
      GSA vs rERL-GSA, 0.77 vs 0.62 [p = 0.0004]; for ARL-LHL15 vs ERL-LHL15, 0.79 vs
      0.64 [p = 0.0005]; and for ARL-Rmax vs ERL-Rmax, 0.78 vs 0.66 [p = 0.0003]).
      According to multivariate analysis, each of three ARL parameters was identified
      as an independent predictor of PHLF (p < 0.0001 for all). CONCLUSION: Technetium
      99m-labeled GSA scintigraphy is useful for predicting PHLF, particularly for
      applying an accurate resection line on GSA-SPECT images.

PMID- 29023154
TI  - Diagnostic Performance of DWI for Differentiating High- From Low-Grade Clear Cell
      Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: The purpose of our study was to review the diagnostic performance of
      DWI for differentiating high- from low-grade clear cell renal cell carcinoma
      (RCC). MATERIALS AND METHODS: MEDLINE, EMBASE, and Cochrane library databases
      were searched up to March 15, 2017. We included diagnostic accuracy studies that
      used DWI for differentiating high- from low-grade clear cell RCC compared with
      histopathologic results of Fuhrman grade based on nephrectomy or biopsy specimens
      in original research articles. Two independent reviewers assessed methodologic
      quality using the Quality Assessment of Diagnostic Accuracy Studies 2 tool.
      Sensitivity and specificity of the included studies were pooled and graphically
      presented using a hierarchic summary ROC plot. For heterogeneity exploration, we
      assessed the presence of a threshold effect and performed meta-regression
      analyses. RESULTS: Eight retrospective studies (394 patients with 397 clear cell
      RCCs) were included. Pooled sensitivity was 0.78 (95% CI, 0.68-0.85) with a
      specificity of 0.86 (95% CI, 0.70-0.94). A considerable threshold effect was
      observed with a correlation coefficient of 0.811 (95% CI, 0.248-0.964) between
      the sensitivity and false-positive rate. At meta-regression analysis, apparent
      diffusion coefficient (* 10 mm2/s) cutoff value (< 1.57 vs >= 1.57; p = 0.03) and
      location of ROI (solid portion vs whole tumor; p = 0.04) were significant factors
      affecting heterogeneity. Other factors with regard to patients and tumors, study,
      and MRI characteristics were not significant (p = 0.17-0.91). CONCLUSION: DWI
      shows moderate diagnostic performance for differentiating high-from low-grade
      clear cell RCC. Substantial heterogeneity was observed because of a threshold
      effect. Further prospective studies may be needed; all included studies were
      retrospective.

PMID- 29023155
TI  - CSF Venous Fistulas in Spontaneous Intracranial Hypotension: Imaging
      Characteristics on Dynamic and CT Myelography.
AB  - OBJECTIVE: The objective of this study is to describe the anatomic and imaging
      features of CSF venous fistulas, which are a recently reported cause of
      spontaneous intracranial hypotension (SIH). MATERIALS AND METHODS: We
      retrospectively reviewed the records of patients with SIH caused by CSF venous
      fistulas who received treatment at our institution. The anatomic details of each
      fistula were recorded. Attenuation of the veins involved by the fistula was
      compared with that of adjacent control veins on CT myelography (CTM). Visibility
      of the CSF venous fistula on CTM and a modified conventional myelography
      technique we refer to as dynamic myelography was also compared. RESULTS: Twenty
      two cases of CSF venous fistula were identified. The fistulas were located
      between T4 and L1. Ninety percent occurred without a concurrent epidural CSF
      leak. In most cases (82%), the CSF venous fistula originated from a nerve root
      sleeve diverticulum. On CTM, the abnormal veins associated with the CSF venous
      fistula were seen in a paravertebral location in 45% of cases, centrally within
      the epidural venous plexus in 32%, and lateral to the spine in 23%. Differences
      in attenuation between the fistula veins and the control veins was highly
      statistically significant (p < 0.0001), with a threshold of 70 HU perfectly
      discriminating fistulas from normal veins in our series. When both CTM and
      dynamic myelography were performed, the fistula was identified on both modalities
      in 88% of cases. CONCLUSION: CSF venous fistulas are an important cause of SIH
      that can be detected on both CTM and dynamic myelograph y and may occur without
      an epidural CSF leak. Familiarity with the imaging characteristics of these
      lesions is critical to providing appropriate treatment to patients with SIH.

PMID- 29023156
TI  - Stem Cell Therapy for Articular Cartilage Repair: Review of the Entity of Cell
      Populations Used and the Result of the Clinical Application of Each Entity.
AB  - BACKGROUND: Following successful preclinical studies, stem cell therapy is
      emerging as a candidate for the treatment of articular cartilage lesions. Because
      stem cell therapy for cartilage repair in humans is at an early phase, confusion
      and errors are found in the literature regarding use of the term stem cell
      therapy in this field. PURPOSE: To provide an overview of the outcomes of
      cartilage repair, elucidating the various cell populations used, and thus reduce
      confusion with regard to using the term stem cell therapy. STUDY DESIGN:
      Systematic review. METHODS: The authors systematically reviewed any studies on
      clinical application of mesenchymal stem cells (MSCs) in human subjects. A
      comprehensive search was performed in MEDLINE, EMBASE, the Cochrane Library,
      CINAHL, Web of Science, and Scopus for human studies that evaluated articular
      cartilage repair with cell populations containing MSCs. These studies were
      classified as using bone marrow-derived MSCs, adipose tissue-derived MSCs,
      peripheral blood-derived MSCs, synovium-derived MSCs, and umbilical cord blood
      derived MSCs according to the entity of cell population used. RESULTS: Forty-six
      clinical studies were identified to focus on cartilage repair with MSCs: 20
      studies with bone marrow-derived MSCs, 21 studies with adipose tissue-derived
      MSCs, 3 studies with peripheral blood-derived MSCs, 1 study with synovium-derived
      MSCs, and 1 study with umbilical cord blood-derived MSCs. All clinical studies
      reported that cartilage treated with MSCs showed favorable clinical outcomes in
      terms of clinical scores or cartilage repair evaluated by MRI. However, most
      studies were limited to case reports and case series. Among these 46 clinical
      studies, 18 studies erroneously referred to adipose tissue-derived stromal
      vascular fractions as "adipose-derived MSCs," 2 studies referred to peripheral
      blood-derived progenitor cells as "peripheral blood-derived MSCs," and 1 study
      referred to bone marrow aspirate concentrate as "bone marrow-derived MSCs."
      CONCLUSION: Limited evidence is available regarding clinical benefit of stem cell
      therapy for articular cartilage repair. Because the literature contains
      substantial errors in describing the therapeutic cells used, researchers need to
      be alert and observant of proper terms, especially regarding whether the cells
      used were stem cells or cell populations containing a small portion of stem
      cells, to prevent confusion in understanding the results of a given stem cell
      based therapy.

PMID- 29023157
TI  - Public Health and School Nurses' Perceptions of Barriers to HPV Vaccination in
      Missouri.
AB  - Human Papilloma Virus (HPV) is associated with various forms of cancer and is
      preventable with vaccination. Nurses are in a unique position to directly
      influence a person's decision to receive the HPV vaccine. A statewide sample of
      both school and public health nurses was used to assess knowledge and attitudes
      related to the HPV vaccine as well as nurse's behaviors and behavioral intentions
      toward educating parents and recommending the vaccine. Positive attitudes and
      adequate knowledge levels were found, however, the majority of school nurses did
      not provide information and resources to parents. Targeted health promotion
      programs for school nurses are recommended.

PMID- 29023158
TI  - Healthy Families: A Family-Based Community Intervention To Address Childhood
      Obesity.
AB  - The objective of this study was to determine the effectiveness of Healthy
      Families, a family-based community intervention, in improving the knowledge, self
      efficacy, and health behaviors of overweight/obese children and their families as
      well as to explore the lessons learned. Results showed families who completed the
      program had significant improvements for children and parents in areas such as
      nutrition knowledge and self-efficacy in making healthy eating choices as well as
      participating in physical activity. Additionally, families reported decreasing
      their intake of sugar-sweetened beverages. Participating families and community
      partners provided valuable lessons for other communities seeking to implement a
      similar program.

PMID- 29023160
TI  - Collaborating with Public Housing Residents and Staff to Improve Health: A Mixed
      Methods Analysis.
AB  - This study described the health behaviors and barriers and facilitators of those
      behaviors in elderly and/or disabled residents of public housing. A mixed-methods
      design was used. Residents (N = 88) completed a survey with validated measures of
      health behaviors. A sub-sample (N = 16) participated in three focus groups.
      Residents scored worse than population norms on the majority of behaviors
      measured. Qualitative results framed in an ecological model indicated the
      majority of facilitators and barriers to health behaviors were perceived as
      occurring at the intrapersonal and interpersonal levels. Interventions to promote
      health should consider the unique barriers and facilitators to health behaviors
      among residents.

PMID- 29023161
TI  - An Integrative Review of Factors Associated with Patient Attrition from Community
      Health Worker Programs that Support Diabetes Self-Care.
AB  - An integrative review was conducted using PubMed and CINAHL databases to answer:
      What is known about adult attrition from community health worker (CHW) programs
      on diabetes self-care? The 14 articles described patients of multiple races who
      were mainly of lower socioeconomic status. CHW interventions were given in
      individual meetings and/or group sessions. Incentives to reduce attrition came in
      different forms. Barriers involved transportation, family obligations, and
      scheduling conflicts. Attrition from these programs is a multifactorial problem.
      Alleviating transportation barrier appears to be protective. Program planners
      should consider these barriers when planning CHW programs.

PMID- 29023162
TI  - Bullying: Effects on School-Aged Children, Screening Tools, and Referral Sources.
AB  - Bullying is not a new concept or behavior, and is now gaining national attention
      as a growing public health concern. Bullying leads to short- and long-term
      physical and psychological damage to both the victims and the bullies. The
      serious implications of bullying drive a clinical mandate for teachers and school
      nurses to be educated and adequately trained to identify and address bullying
      within schools. This review of the literature describes screening tools that can
      be utilized to identify both victims and bullies. In addition, referral services
      utilizing collaborative intervention measures are discussed. This literature
      review will help school nurses and teachers to identify and expand their role in
      school-wide bullying prevention and intervention measures.

PMID- 29023163
TI  - Asthma exacerbations and socio-economic status in French adults with persistent
      asthma: A prospective cohort study.
AB  - INTRODUCTION: Adults disadvantaged by poor socio-economic status (SES) are more
      severely affected by asthma compared to those with better SES. We aimed to
      determine whether the frequency of asthma exacerbations (AEx), as well as aspects
      related to AEx management, differed based on SES in patients treated with daily
      treatments. METHODS: This study, part of the prospective observational cohort
      ASTRO-LAB, included French adult patients with persistent asthma. Patients were
      considered as low SES if they benefited from publicly funded special health
      insurance and/or were perceived as low SES by their general practitioner. AEx was
      defined as at least one of the following: asthma-related oral corticosteroid
      course, medical contact, hospitalization, and death. We examined associations
      between SES and AEx frequency, perceived triggering factors and type of medical
      contact after AEx. RESULTS: In our sample of 255 patients, 11.40% were considered
      as low SES. Patients with low SES did not report significantly more AEx than
      medium/high SES patients during one-year follow-up (0.79 versus 0.55, p = 0.38).
      The type of medical contact during AEx differed significantly between the two
      groups (p = 0.03): patients with medium/high SES consulted their general
      practitioner more frequently (OR = 2.23, 95% CI = 0.91-5.50, p = 0.08) and were
      less likely to visit an emergency department or be hospitalized (OR = 0.27, 95%
      CI = 0.09-0.84, p = 0.02). CONCLUSIONS: AEx frequency did not differ
      significantly between low and medium/high SES patients, but differences were
      found in the management of AEx. Studies are needed to better understand the
      relation between precariousness and management of asthma.

PMID- 29023165
TI  - Clinical Characteristics of Ocular Sarcoidosis: A Population-Based Study 1976
      2013.
AB  - PURPOSE: To characterize the epidemiology and clinical characteristics of ocular
      involvement in patients with systemic sarcoidosis. METHODS: An inception cohort
      of patients with systemic sarcoidosis in 1976-2013 in Olmsted County, Minnesota,
      was identified based on comprehensive individual medical record review. Medical
      records of those patients were then reviewed for ocular involvement. RESULTS: A
      total of 345 incident cases of systemic sarcoidosis were identified. Ocular
      involvement occurred in 23 patients (7%). The most common ocular disease was
      uveitis (61%) followed by dry eye disease, conjunctival nodule, episcleritis,
      anterior scleritis, and conjunctivitis. Anterior uveitis was the most common type
      of uveitis (71%). The visual outcome of uveitis was favorable with only one
      patient lost three or more lines of VA during follow-up and had VA of less than
      20/200 at last visit. CONCLUSION: Ocular involvement occurred in 7% of
      sarcoidosis patients. Uveitis was the most common type of ocular disease.

PMID- 29023166
TI  - Prehospital Stroke Assessment for Large Vessel Occlusions: A Systematic Review.
AB  - BACKGROUND AND OBJECTIVE: Stroke is the leading cause of disability in the United
      States and new evidence shows interventional procedures provide better outcomes
      for large vessel occlusions (LVO). We performed a systematic review of the
      literature on prehospital stroke scales used to identify LVOs comparing the
      scales with analysis of the sensitivity, specificity, and predictive values. The
      goal was to determine if emergency medical services (EMS) are able to accurately
      identify LVO in the field. METHODS: In this systematic review, multiple databases
      were searched for articles that addressed our goal. The identified studies were
      evaluated for their statistical performance of various stroke scales. In
      addition, we assessed biases that may explain the varying results reported.
      RESULTS: Eight studies encompassing 6787 patients were included in our systematic
      review. Of the 8 studies, 6 were retrospective studies, 1 was a prospective
      cohort, and 1 was a prospective observational study. Sensitivities of the studies
      ranged from 49% to 91% while specificity of the studies varied from 40% to 94%.
      CONCLUSION: At this time, further evaluations must be done in the prehospital
      setting to determine the ease of use and true sensitivity and specificity of
      these scales in identifying LVOs.

PMID- 29023167
TI  - State Regulation of Community Paramedicine Programs: A National Analysis.
AB  - BACKGROUND: Community Paramedicine (CP) is a rapidly evolving field within
      prehospital care where paramedics step outside of their traditional roles of
      treating acute conditions to provide elements of primary and preventive care. It
      is unclear if current state oversight regarding the scope of practice (SOP) for
      paramedics provides clear guidance on the novel functions provided and skills
      performed by CP programs. OBJECTIVE: To determine the process and authority, as
      currently defined by state laws and regulations in the United States, to expand
      paramedic SOP in order to perform CP roles and to assess state EMS agencies'
      interpretation of paramedic SOP as it applies to CP. METHODS: We conducted a
      systematic review of laws, regulations, and policies from the 50 U.S. states in
      effect between February and June 2016 that define or apply to paramedic SOP. We
      determined whether each state's SOP included 21 potential skills applicable to CP
      within the following categories: assessment, treatment & intervention, referrals,
      and prevention & public health. Laws were also queried for mechanisms for
      expanding SOP, alternate destinations, and community paramedicine for each state.
      Additionally, we surveyed representatives from U.S. State Emergency Medical
      Services (EMS) agencies and asked which of these skills were a part of their
      current SOP. All data was coded into ExcelTM and analyzed using descriptive
      statistics. RESULTS: All 50 U.S. states have laws relating to EMS. Forty-one
      states have a statewide SOP (82%), and 3 states have statewide protocols from
      which the SOP has been inferred for purposed of this study, but may not legally
      constitute SOP in this jurisdiction (6%). 20 states (40%) had a clearly defined
      mechanism for expanding SOP. Sixteen states (32%) had laws specific to CP. Seven
      states (14%) allowed for patients to be transported to alternate destinations. Of
      the 21 skills surveyed, on average there were 8.63 (6.41-10.85) fewer skills for
      paramedics found in state SOP laws and regulations than were reported as being a
      part of a state's paramedic SOP. All skills demonstrated variability between the
      legal review and survey results with 13.04-96.15% concordance. CONCLUSION: There
      is a lack of guidance and consistency regarding CP programs and scope of
      practice. Further studies are needed to understand best practices around
      regulation and oversight of CP.

PMID- 29023168
TI  - Development and characterization of cationic solid lipid nanoparticles for co
      delivery of pemetrexed and miR-21 antisense oligonucleotide to glioblastoma
      cells.
AB  - The practical use of solid lipid nanoparticles (SLNs) in research has been
      highlighted in the literature, but few reports have combined SLNs with miRNA
      based therapy and chemotherapy. We aimed to prepare cationic SLNs (cSLNs) to load
      anti-miR-21 oligonucleotide and pemetrexed for glioblastoma therapy in vitro.
      cSLNs were employed to encapsulate both pemetrexed and anti-miR-21 by a high
      pressure homogenization method, and then the properties of cSLNs were
      characterized. We studied cellular uptake and cytotoxicity properties of cSLNs in
      U87MG cells. cSLNs were 124.9 +/- 1.6 nm in size and 27.3 +/- 1.6 mV in zeta
      potential with spherical morphology in the TEM image. cSLNs uptake by U87MG cells
      was increased significantly higher and more effective than free pemetrexed. These
      findings suggest that cSLNs represent a potential new approach for carrying both
      pemetrexed and anti-miR-21 for glioblastoma therapy.

PMID- 29023169
TI  - Associations of Physical Activity and Sedentary Behaviour with Vision-Threatening
      Diabetic Retinopathy in Indonesian Population with Type 2 Diabetes Mellitus:
      Jogjakarta Eye Diabetic Study in the Community (JOGED.COM).
AB  - PURPOSE: To investigate the association of physical activity (PA) and sedentary
      behaviour with diabetic retinopathy (DR) in type 2 diabetes adults. METHODS: A
      community-based cross-sectional study of adults with type 2 diabetes. DR was
      assessed from disc- and macula-centred fundus photograph, and categorised into
      mild, moderate non-proliferative DR (NPDR), and Vision-Threatening DR (VTDR).
      Worse eye was used to determine the person's DR severity. PA was assessed using
      WHO Global Physical Activity Questionnaire (GPAQ). All of the PA components,
      including daily sitting time, walking distance, sleeping duration, and exercise
      were converted based on the physical activity ratio and then calculated to obtain
      the mean physical activity level (PAL). The mean PAL was then classified into
      sedentary, moderate, and vigorous lifestyle. RESULTS: There were 1116
      participants, 43.1% with any DR and 26.3% VTDR. The prevalence of DR/VTDR in
      sedentary, moderate, and vigorous physical activity group was 41.9%/22.7%,
      39.2%/23.9%, and 32.7%/20.4% respectively. A longer duration of daily sedentary
      lifestyle (>3 hours) was significantly associated with presence of DR (OR 1.66;
      95% CI 1.17-2.35; p < 0.01) and VTDR (OR 1.74; 1.16-2.62; p < 0.01). These
      associations remained significant after adjusting for age, gender, duration of
      diabetes, systolic blood pressure and physical activity. There was no significant
      association between sleeping duration, walking distance, and vigorous activity
      and DR. CONCLUSIONS: In this study, prolonged daily sedentary activity was
      strongly associated with VTDR. This finding suggests that public health campaign
      for reducing daily sedentary activities in individuals with type 2 diabetes may
      offer benefit to reduce the burden of DR and VTDR.

PMID- 29023170
TI  - AMPA receptors and perampanel behind selected epilepsies: current evidence and
      future perspectives.
AB  - INTRODUCTION: The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      (AMPA) receptors are the major mediators of glutamate-mediated excitatory
      neurotransmission, and are critical for synchronization and spread of epileptic
      activity. Areas covered: AMPA receptor antagonists have been also developed as
      antiepileptic drugs and perampanel (PER) is the first highly selective, non
      competitive AMPA-type glutamate receptor antagonist that is available on the
      market. It is approved as adjunctive therapy for the treatment of partial-onset
      seizures with or without secondary generalization, and for primary generalized
      tonic-clonic seizures in idiopathic generalized epilepsy, in patients aged >= 12
      years. This article reviews the role of AMPA receptors in the neuronal
      hyperexcitability underlying epilepsy, the mechanism of action and clinical
      experience on the anti-seizure activity of PER. Moreover, the rationale for
      targeting AMPA receptor in specific epileptic disorders, including brain tumor
      related epilepsy, mesial temporal lobe epilepsy with/without hippocampal
      sclerosis, and status epilepticus is evaluated. Finally, the pharmacological
      rationale for the development of AMPA receptor antagonists in other neurological
      disorders beyond epilepsy is considered. Expert opinion: Further research aimed
      at better understanding the pharmacology and blocking mechanism of PER and other
      AMPA receptor antagonists will drive future development of therapeutic agents
      that target epilepsy and other neurological diseases.

PMID- 29023171
TI  - Anemia in children: prevalence, causes, diagnostic work-up, and long-term
      consequences.
AB  - INTRODUCTION: Anemia in children is a major public health problem throughout the
      world. It is often multifactorial, iron deficiency being the most frequent
      etiology. Consequences are diverse and largely under evaluated. Areas covered:
      This paper briefly reviews the main causes and focus on the potential
      consequences of acute and chronic anemia in children. Expert commentary: Anemia
      in children should never be trivialized. Even if iron deficiency is frequently
      involved, other potentially life-threatening causes are possible and should be
      looked for. The exact contribution of anemia to child mortality and morbidity is
      difficult to assess because of overlapping comorbidities. Chronic anemia may
      impair growth, cardiac function and cognitive development in infants but other
      consequences are rather poorly described and should be explored more thoroughly.

PMID- 29023172
TI  - Basic and Advanced EMS Providers Are Equally Effective in Naloxone Administration
      for Opioid Overdose in Northern New England.
AB  - OBJECTIVE: Overdose mortality from illicit and prescription opioids has reached
      epidemic proportions in the United States, especially in rural areas. Naloxone is
      a safe and effective agent that has been shown to successfully reverse the
      effects of opioid overdose in the prehospital setting. The National EMS Scope of
      Practice Model currently only recommends advanced life support (ALS) providers to
      administer naloxone; however, some individual states have expanded this scope of
      practice to include intranasal (IN) administration of naloxone by basic life
      support (BLS) providers, including the Northern New England states. This study
      compares the effectiveness and appropriateness of naloxone administration between
      BLS and ALS providers. METHODS: All Vermont, New Hampshire, and Maine EMS patient
      encounters between April 1, 2014 and December 31, 2016 where naloxone was
      administered were examined and 3,219 patients were identified. The proportion of
      successful reversals of opioid overdose, based on improvement in the Glasgow Coma
      Scale (GCS), respiratory rate (RR), and provider global assessment (GA) of
      response to medication was compared between BLS and ALS providers using a Chi
      Squared statistic, Fisher's exact or Wilcoxon rank-sum test. RESULTS: There was
      no significant difference in the percent improvement in GCS between BLS and ALS
      (64% and 64% P = 0.94). There was no significant difference in the percentage of
      improvement in RR between BLS and ALS (45% and 48% P = 0.43). There was a
      significant difference in the percentage of improvement of GA between BLS and ALS
      (80% and 67% P < 0.001). There was no significant difference in determining
      appropriate cases to administer naloxone where RR < 12 and GCS < 15 between BLS
      and ALS (42% and 43% P = 0.94). CONCLUSIONS: BLS providers were as effective as
      ALS providers in improving patient outcome measures after naloxone administration
      and in identifying patients for whom administration of naloxone is appropriate.
      These findings support expanding the National EMS Scope of Practice Model to
      include BLS administration of intranasal naloxone for suspected opioid overdoses.

PMID- 29023173
TI  - Health science center faculty attitudes towards interprofessional education and
      teamwork.
AB  - The attitudes of faculty towards interprofessional education (IPE) and teamwork
      impact the education of health professions education (HPE) students. This paper
      reports on a study evaluating attitudes from health professions educators towards
      IPE and teamwork at one academic health science center (HSC) where modest IPE
      initiatives have commenced. Drawing from the results of a previous investigation,
      this study was conducted to examine current attitudes of the faculty responsible
      for the training of future healthcare professionals. Survey data were collected
      to evaluate attitudes from HSC faculty, dentistry, nursing, medicine, pharmacy
      and public health. In general, positive HSC faculty attitudes towards
      interprofessional learning, education, and teamwork were significantly predicted
      by those affiliated with the component of nursing. Faculty development aimed at
      changing attitudes and increasing understanding of IPE and teamwork are critical.
      Results of this study serve as an underpinning to leverage strengths and evaluate
      weakness in initiating IPE.

PMID- 29023174
TI  - Subjective responses to sprint interval exercise in adults with and without
      Exercise-induced bronchoconstriction.
AB  - OBJECTIVE: Little is known of the subjective response to exercise that involves
      short "all out" bursts of effort, separated by recovery periods (sprint interval
      exercise (SPRINT)) among adults with exercise-induced bronchoconstriction (EIBC).
      The purpose of this study was to compare subjective responses to SPRINT and
      moderate intensity continuous exercise (MOD) among adults with EIBC, and to
      compare these responses between adults with EIBC and those without EIBC. METHODS:
      Eight adults (22.3 +/- 3.0 years) with EIBC, and eight adults (22.3 +/- 3.0
      years) without EIBC completed a SPRINT (4 * 30 second sprints separated by 4.5
      minutes of active recovery) and MOD (20 minutes at 65% peak power output) session
      in random order. Self-reported affect, perceived breathlessness, and perceived
      exertion were recorded throughout exercise using validated scales. Enjoyment was
      assessed following exercise. RESULTS: Differences between SPRINT and MOD were
      observed such that affect and perceived breathlessness were worse during the
      initial stages of SPRINT than MOD; however, differences disappeared by the end of
      exercise. Enjoyment was similar for SPRINT and MOD in the EIBC group (SPRINT:
      72.9 +/- 20.0 vs. MOD: 79.5 +/- 20.5, p = 0.25), and between groups for SPRINT
      and MOD. CONCLUSIONS: Perceived breathlessness may impact affect during the early
      stages of exercise among those with EIBC. Post-exercise enjoyment appears to be
      similar between SPRINT and MOD. Future research is needed to better understand
      the relationship between ventilation patterns, exercise intensity, and enjoyment
      of exercise among those with EIBC.

PMID- 29023175
TI  - Complications and outcomes of grafting of posterior orbital fat into the lower
      lid-cheek junction during orbital decompression.
AB  - PURPOSE: To report the complications of grafting of excised posterior orbital fat
      into the lower lid-cheek junction at the time of orbital decompression surgery.
      METHODS: Retrospective review of consecutive patients undergoing orbital
      decompression combined with grafting of posterior orbital fat to the pre-malar
      and lateral canthal area (FG). A second group of consecutive patients undergoing
      orbital decompression but no orbital fat grafting (NoFG) were also studied as a
      form of comparative control. Standard patient data, including age, sex, visual
      acuity, degree of proptosis, operative details, diplopia or any other
      complications was collected. Independent assessment of pre- and post-operative
      photographs graded the lower lid-cheek junction. RESULTS: Thirty-four orbits of
      29 patients, of which 21 orbits underwent orbital decompression with orbital fat
      grafting (FG). There were no intraoperative complications, postoperative
      infections, or visual loss. Complications relating to fat grafting included
      prolonged swelling in 3 (17%) patients at 3 months, in 1 case lasting 6 months,
      lower lid lumps in 3 (17%), and fat seepage in 1 (6%). The FG group achieved a
      greater improvement in the appearance of the lower-lid-cheek junction at 12
      months in comparison to NoFG. Mean grade improvement 1.24 +/- 1.09 vs 0 +/- 0.82
      (p = 0.025). Median follow-up was 20 months (range 6-30 months). CONCLUSION:
      Grafting of excised orbital fat during orbital decompression can improve the
      appearance of the lower lid-cheek junction in patients being treated for thyroid
      orbitopathy. However, 24% of patients will experience swelling and/or lumpiness
      requiring several months to settle or further fat excision.

PMID- 29023176
TI  - Induction of Vogt-Koyanagi-Harada Disease by Interferon-Alpha and Ribavirin
      Treatment in Patients with Hepatitis C: A Case Report and Review of the
      Literature.
AB  - PURPOSE: To describe a case of Vogt-Koyanagi-Harada disease (VKH) presenting in a
      hepatitis C patient after interferon-alpha (IFN-alpha) and ribavirin treatment.
      METHODS: A retrospective review of our patient and a review of the published
      literature. RESULTS: A 59 year-old man developed VKH after the four months of IFN
      alpha and ribavirin therapy for hepatitis C. The patient's VKH was controlled by
      systemic corticosteroids. The relationship between VKH and IFN-alpha is discussed
      based on the published literature. CONCLUSIONS: VKH is a rare autoimmune
      complication triggered by interferon-alpha therapy; the T-cell modulatory
      properties of IFN-alpha possibly contribute to this association. Early diagnosis
      of VKH and aggressive systemic corticosteroid intervention are essential for this
      type of IFN-alpha -related autoimmune complication.

PMID- 29023177
TI  - Is Remote Ischemic Conditioning of Benefit to Patients Undergoing Kidney
      Transplantation?
AB  - Renal ischemia-reperfusion injury (IRI), an inevitable event during kidney
      transplantation procedure, can result in delayed graft function or even primary
      nonfunction. In addition to strategies to limit IRI such as advancements in organ
      allocation systems and preservation of organs, and reduction in cold and warm
      ischemia time, remote ischemic conditioning (RIC) has attracted much attention in
      recent years. With promising findings and data suggesting a potential benefit of
      RIC in animal kidney transplantation models, a few clinical trials have
      investigated the use of RIC in human kidney transplantation. Unfortunately, the
      findings from these investigations have been inconclusive due to a number of
      factors such as diverse time points of RIC, limited sample size, and complexity
      of kidney transplant patients. This brief commentary aims to discuss the effects
      of RIC on clinical outcomes and proinflammatory cytokines in patients undergoing
      kidney transplantation.

PMID- 29023178
TI  - Effect of Calcium Derived from Lithothamnion sp. on Markers of Calcium Metabolism
      in Premenopausal Women.
AB  - A double-blind crossover pilot trial tested the hypothesis that botanically
      derived calcium could demonstrate greater influence over calcium metabolism
      markers compared with a nonplant-derived calcium carbonate supplement or placebo.
      Twelve fasting female subjects received a single oral dose of Aquamin FTM
      (derived from the marine algal Lithothamnion sp.), or calcium carbonate, or
      placebo. Blood and urine samples were collected at baseline and over 12 h to
      evaluate ionized and total calcium and parathyroid hormone (PTH). Subjects
      treated with Aquamin F demonstrated significantly greater urinary clearance of
      calcium after 12 h compared with placebo (P = .004). Following a meal at 90 min,
      subjects treated with Aquamin F demonstrated a more prolonged suppression of
      serum PTH concentration (significantly lower than placebo at 90, 120, and 240
      min). Calcium carbonate provided an intermediate response; urinary clearance was
      not significantly different from placebo treatment and PTH was only significantly
      lower than placebo at 90 min. Aquamin F may demonstrate greater influence over
      these markers of calcium metabolism than calcium carbonate or placebo, as
      suggested by a greater calciuric response and a more prolonged suppression of
      serum PTH concentrations following a meal in premenopausal women.

PMID- 29023179
TI  - Effect of platelet-rich plasma on patients after blepharoplasty surgery.
AB  - AIM: To evaluate the effect of platelet-rich plasma (PRP) treatment on patients
      after blepharoplasty surgery. MATERIALS AND METHODS: After undergoing
      blepharoplasty, 20 patients were randomly divided into two groups (n = 10 each).
      One was treated with autologous PRP and the other was not given any post-surgery
      treatment (basal group). Autologous PRP application was performed intradermically
      24 h, 1 month, and 2 months post-surgery, and the outcome of the applications was
      assessed 1, 2, and 3 months post-surgery. The postoperative wound was assessed on
      a patient and observer scar assessment scale (POSAS) by patients and by an
      unblinded clinical observer. Statistical comparison between the two groups was
      analyzed by using the Mann-Whitney unpaired, two-tailed test. Significant
      differences were considered with P <= 0.05. RESULTS: Patient-reported data
      indicate that compared to the basal group, the PRP group showed no significant
      differences regarding pain, itching, or color, but had better values for
      stiffness and thickness (months 1 and 2) as well as scar irregularity (month 1).
      Data reported by the clinical observer showed that in comparison with the basal
      group, the PRP group showed no differences in vascularization or pigmentation,
      but had lower (better) scores regarding thickness, relief, and pliability (at all
      assessment times). The total assessment values from patients and the observer
      were significantly better for the PRP than the basal group. CONCLUSION:
      Autologous PRP treatment enhanced some parameters associated with healing
      properties, suggesting a potential therapeutic value after blepharoplasty
      surgery.

PMID- 29023181
TI  - Review for Disease of the Year: Varicella Zoster Virus-Induced Anterior Uveitis.
AB  - Varicella zoster virus (VZV)-induced anterior uveitis (AU) may complicate the
      course of primary varicella infection typically seen in children. In adults,
      especially with advanced age, VZV AU is more commonly associated with herpes
      zoster ophthalmicus (HZO) with or without skin rash affecting the distribution of
      the ophthalmic nerve due to reactivation of the latent VZV in the trigeminal
      ganglion. While it is typically a mild self-limiting AU in primary infection, HZO
      AU is often accompanied by keratitis, may have a chronic recurrent course, and
      lead to sectoral iris atrophy, pupillary distortion, and ocular hypertension.
      Diagnosis is often clinical and proven by analysis of aqueous humor for viral
      genome or antiviral antibodies. Systemic antiviral agents and topical steroids
      are the mainstay of treatment. Visual prognosis is favorable with timely
      diagnosis and appropriate treatment.

PMID- 29023180
TI  - Trends in Early Prenatal Care Among Women with Pre-Existing Diabetes: Have Income
      Disparities Changed?
AB  - BACKGROUND: Women with pre-existing diabetes are at high maternal risk for
      comorbidities and death, particularly when early prenatal care is not received.
      Low income is a known barrier to early prenatal care. It is unknown whether
      recent policies to expand access to prenatal care have reduced income
      disparities. We hypothesized that income disparities would be minimized and that
      the odds of receipt of first trimester prenatal care among women with pre
      existing diabetes would become similar across income strata over time. MATERIAL
      AND METHODS: Using the Colorado birth certificate registry from 2007 to 2014,
      receipt of prenatal care was assessed retrospectively in 2,497 women with pre
      existing diabetes. Logistic regression was used to examine the association
      between high (>$50,000), medium ($25,000-50,000), and low (<$25,000) income
      strata and receipt of first trimester prenatal care by birth year, adjusted for
      demographics. RESULTS: High, medium, and low income represented 29.5%, 19.0%, and
      51.5% of the cohort, respectively. Women with high income were more likely to
      receive first trimester care than women with low income from 2007 [adjusted odds
      ratio, 95% confidence interval: 2.16 (1.18, 3.96)] through 2013 [1.66 (1.01,
      2.73)], but significant differences were no longer observed in 2014 [1.59 (0.89,
      2.84)]. The likelihood of receiving first trimester prenatal care was not
      significantly different between medium- and low-income strata from 2007 [1.07
      (0.66, 1.74)] through 2014 [0.77 (0.48, 1.23)]. CONCLUSIONS: From 2007 to 2013,
      women in Colorado with diabetes were more likely to receive early prenatal care
      if they were in the highest income stratum than in the lowest stratum. In 2014,
      receipt of first trimester care became equitable across all income strata. Future
      work should examine national patterns of income with receipt of prenatal care and
      outcomes among women with pre-existing diabetes.

PMID- 29023182
TI  - Potential clinical utility of multiple system atrophy biomarkers.
AB  - INTRODUCTION: Multiple system atrophy (MSA), an adult-onset, fatal disorder of
      uncertain etiology, characterized by parkinsonism, cerebellar, autonomic and
      motor dysfunctions, is an alpha-synucleinopathy with glioneuronal degeneration
      involving multiple parts of the nervous system. The clinical variants correlate
      with the morphological phenotypes of striatonigral degeneration (MSA-P),
      olivoponto-cerebellar atrophy (MSA-C), and mixed type MSA. Neuropathological
      hallmark is the deposition of aberrant alpha-synuclein in glia and neurons
      forming cytoplasmic inclusions that cause cell dysfunction/demise. Areas covered:
      While our knowledge of the pathogenesis of this proteinopathy is still
      incomplete, updated consensus criteria and combined biomarkers have increased
      diagnostic accuracy. Multimodal imaging of structural and functional brain
      changes gives insight into the pathophysiology and may evaluate disease
      progression. Currently, the most useful CSF biomarkers are a combination of light
      chain neurofilament (elevated in MSA), catecholaminergic metabolites, and
      proteins (alpha-synuclein, DJ-1, tau). Several blood substances (neurofilament
      light chain, microRNAs) are non-invasive biomarkers. Expert commentary: Recent
      studies suggest that the combination of neuroimaging and fluid biomarkers may be
      more successful than using single markers to increase the accuracy of the
      clinical (differential) diagnosis of MSA. Multidisciplinary research to develop
      more reliable markers for a more exact and early diagnosis and targets for
      effective treatment are urgently needed.

PMID- 29023183
TI  - Attachment and Effortful Control in Toddlerhood Predict Academic Achievement Over
      a Decade Later.
AB  - A child's attachment to his or her caregiver is central to the child's
      development. However, current understanding of subtle, indirect, and complex long
      term influences of attachment on various areas of functioning remains incomplete.
      Research has shown that (a) parent-child attachment influences the development of
      effortful control and that (b) effortful control influences academic success. The
      entire developmental cascade among these three constructs over many years,
      however, has rarely been examined. This article reports a multimethod, decade
      long study that examined the influence of mother-child attachment and effortful
      control in toddlerhood on school achievement in early adolescence. Both
      attachment security and effortful control uniquely predicted academic achievement
      a decade later. Effortful control mediated the association between early
      attachment and school achievement during adolescence. This work suggests that
      attachment security triggers an adaptive cascade by promoting effortful control,
      a vital set of skills necessary for future academic success.

PMID- 29023185
TI  - Effectiveness of Low-Intensity Laser Therapy on Tissue Repair Following
      Saphenectomy in Patients Who Underwent Coronary Artery Bypass Graft: A
      Randomized, Double-Blind Study.
AB  - OBJECTIVE: To verify the effectiveness of low-intensity laser therapy (LLLT) on
      tissue repair following saphenectomy during postoperative period in patients
      having undergone coronary artery bypass graft (CABG). MATERIALS AND METHODS: A
      randomized clinical trial, controlled and double-blind study was conducted with
      40 volunteers, divided into 2 groups: a placebo group (PG, n = 20) and a laser
      group (LG, n = 20). The patients in the LG group were irradiated with laser
      during saphenectomy (InGaAlP, lambda 660 nm, energy density 6 J/cm2) daily from
      the first to the fourth postoperative day. The surgical incision was clinically
      evaluated and imaged at the beginning and at the end of the treatment. The areas
      of hematoma and hyperemia were evaluated using the software ImageJ 1.4(c), and
      border closure was evaluated by three researchers, who were blinded concerning
      the allocation of the participants. RESULTS: The LG group presented a reduction
      of the areas of hematoma and hyperemia (p = 0.0003) and better border closure (p
      = 0.009), when compared with the PG group. CONCLUSIONS: The proposed LLLT
      protocol improved the tissue repair following saphenectomy in CABG patients.

PMID- 29023184
TI  - Disease-associated protein seeding suggests a dissociation between misfolded
      protein accumulation and neurodegeneration in prion disease.
AB  - Chronic neurodegenerative diseases, such as prion diseases or Alzheimer's
      disease, are associated with progressive accumulation of host proteins which
      misfold and aggregate. Neurodegeneration is restricted to specific neuronal
      populations which show clear accumulation of misfolded proteins, whilst
      neighbouring neurons remain unaffected. Such data raise interesting questions
      about the vulnerability of specific neuronal populations to neurodegeneration and
      much research has concentrated only on the mechanisms of neurodegeneration in
      afflicted neuronal populations. An alternative, undervalued and almost completely
      unstudied question however is how and why neuronal populations are resilient to
      neurodegeneration. One potential answer is unaffected regions do not accumulate
      misfolded proteins, thus mechanisms of neurodegeneration do not become activated.
      In this perspectives, we discuss novel data from our laboratories which
      demonstrate that misfolded proteins do accumulate in regions of the brain which
      do not show evidence of neurodegeneration and further evidence that microglial
      responses may define the severity of neurodegeneration.

PMID- 29023186
TI  - Photodynamic Therapy Associated with a Blue Dye Papain-Based Gel and Evaluation
      of Its Degradation of Type I Collagen Fibers.
AB  - OBJECTIVE: The aim of this in vitro study was to evaluate the degradation of type
      I collagen fibers after treatment with a papain-based gel associated with a blue
      dye (PapaMBlueTM) for use in antimicrobial photodynamic therapy. MATERIALS AND
      METHODS: For such, 60 bioabsorbable membrane sponge discs were used. Group 1 was
      the negative control group. In groups 2, 3, and 4, the papain-based gel PapaMBlue
      gel was applied all over the samples for 4 min and irradiated using red laser
      (660 +/- 10 nm) with 15, 30, and 40 J/cm2, respectively. In group 5, the papain
      based gel was applied all over the samples for 4 min. In group 6, the
      photosensitizing dye was applied all over the samples for 4 min. The
      compositional analysis of the samples was performed using ATR-FTIR (attenuated
      total reflectance-Fourier transformed infrared spectroscopy). The data were
      statistically analyzed using ANOVA and Tukey's test (p < 0.05). RESULTS: Neither
      classic PapacarieTM nor the modified product with a photosensitizing agent
      (PapaMBlue) promoted collagen degradation. CONCLUSIONS: The irradiation of
      methylene blue added to papain gel with red light did not alter the chemical
      structure of type I collagen.

PMID- 29023187
TI  - Manual Operated Ultraviolet Surface Decontamination for Healthcare Environments.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of a new
      handheld equipment based on a mercury low-pressure vapor lamp. The Surface UV(r)
      device was tested in Staphylococcus aureus, Streptococcus mutans, Streptococcus
      pneumoniae, two strains of Escherichia coli, Pseudomonas aeruginosa, Candida
      albicans, and other clinical microorganisms isolated from different surfaces of a
      public health hospital. BACKGROUND DATA: The incidence of hospital infections has
      increased in recent years. Despite the variety of available chemicals to reduce
      the microorganisms, the search for antimicrobial agents and the characterization
      of novel targets are a continued need. Also, the minimization of chemical
      procedures is a constant need, and the use of ultraviolet (UV) light as a
      germicidal device for microorganisms' inactivation has been an alternative and
      one possible approach for the reduction of contamination. MATERIALS AND METHODS:
      The in vitro decontamination was performed by application of Surface UV in
      different species of microorganisms (study 1). The surface decontamination was
      carried out by application of Surface UV on each surface of hospital environment
      (study 2). The device presents ultraviolet C (UV-C) light at 254 nm and produces
      an irradiance of 13 mW/cm2 at a distance of 1 cm of the surfaces. The light dose
      was 0.78 J/cm2 for 60 sec of application in both studies. RESULTS: The results
      for in vitro decontamination indicated a log10 reduction factor of 6.5 for S.
      aureus, 6.7 for S. mutans, 6.2 for S. pneumoniae, 5.4 for E. coli, 5.2 for E.
      coli (ATCC 8739), 5.4 for P. aeruginosa, and 6.7 for C. albicans. The hospital
      level of microorganisms decreases more by 75% after the procedure. CONCLUSIONS:
      The study highlights the development and successful application of a new portable
      device that can reduce the risk of contamination in health settings. Our results
      suggest that Surface UV is efficient and may be an alternative decontamination
      method.

PMID- 29023188
TI  - Preliminary Experience with Instillation of Triamcinolone Acetonide into the
      Urethra for Idiopathic Urethritis: A Prospective Pilot Study.
AB  - BACKGROUND: Idiopathic bulbar urethritis (IBU) is characterized by hematuria +/-
      dysuria without infection. Symptoms result from inflammation of the bulbar
      urethra, distal to external sphincter. IBU is difficult to manage and there is no
      recommended therapy. OBJECTIVE: To determine whether instillation of
      triamcinolone acetonide is a useful treatment of IBU and its associated
      complications. SETTING AND PARTICIPANTS: Data were prospectively collected, for
      22 months, on 14 consecutive patients presenting with terminal hematuria or blood
      spotting +/- dysuria to a pediatric urology unit. Median age was 12 years (range:
      10-15). Mean symptom duration was 13 months (range: 8-24). Normal baseline
      laboratory blood tests, urine cultures, and ultrasound assessments were seen in
      all; therefore, none were excluded on the basis of a known pathology. Follow-up
      telephone interviews, to assess symptom persistence and side effects, were
      performed at 6 weeks postintervention. The mean follow-up period was 15 months
      (range: 4-20). INTERVENTION: Visual confirmation of IBU was obtained
      cystoscopically and 40 mg of triamcinolone was instilled to the inflamed area
      under direct vision using an open-ended ureteral catheter. OUTCOME MEASUREMENTS:
      Symptoms resolution was the primary outcome. Repeat cystoscopic assessment +/-
      triamcinolone instillation was recorded, as was the occurrence of complications.
      RESULTS AND LIMITATIONS: Seven patients (50%) required at least one further
      treatment. Overall complete or partial resolution was reported in 12/14 patients
      (85.7%). No side effects were reported. CONCLUSIONS: This small prospective
      series demonstrates that intraurethral instillation of triamcinolone seems to be
      a promising treatment option to alleviate inflammatory symptoms in majority of
      cases of idiopathic urethritis. Patient Summary: Fourteen boys with inflammation
      of the urethra, with no identifiable cause, were treated by topically
      triamcinolone, directly to the inflamed area. We demonstrate an 85.7%
      complete/partial resolution of symptoms with no side effects seen.

PMID- 29023191
TI  - Use of Nasogastric Feeding Tubes for Children at Home: A Template for Caregiver
      Education.
AB  - There is a lack of knowledge on the part of caregivers who need to place
      nasogastric (NG) tubes in children for enteral nutrition therapy. This article
      provides the rationale, best practices, and a template for caregiver education.
      Canadian and Australian programs have excellent patient education materials. They
      have shared these step-by-step procedures for healthcare professionals to provide
      to caregivers to whom they are teaching placement and care of NG tubes.

PMID- 29023190
TI  - Effector Biology in Focus: A Primer for Computational Prediction and Functional
      Characterization.
AB  - Plant-pathogen interactions are controlled by a multilayered immune system, which
      is activated by pathogen recognition in the host. Pathogens secrete effector
      molecules to interfere with the immune recognition or signaling network and
      reprogram cell structure or metabolism. Understanding the effector repertoires of
      diverse pathogens will contribute to unraveling the molecular mechanism of
      virulence and developing sustainable disease-control strategies for crops and
      natural ecosystems. Effector functionality has been investigated extensively in
      only a small number of pathogen species. However, many more pathogen genomes are
      becoming available, and much can be learned from a broader view of effector
      biology in diverse pathosystems. The purpose of this review is to summarize
      methodology for computational prediction of protein effectors, functional
      characterization of effector proteins and their targets, and the use of effectors
      as probes to screen for new sources of host resistance. Although these techniques
      were generally developed in model pathosystems, many of the approaches are
      directly applicable for exploration and exploitation of effector biology in
      pathosystems that are less well studied. We hope to facilitate such exploration,
      which will broaden understanding of the mechanisms that underpin the biological
      diversity of plant-pathogen interactions, and maximize the impact of new
      approaches that leverage effector biology for disease control.

PMID- 29023189
TI  - Transfer RNA instability as a stress response in Escherichia coli: Rapid dynamics
      of the tRNA pool as a function of demand.
AB  - Production of the translation apparatus of E. coli is carefully matched to the
      demand for protein synthesis posed by a given growth condition. For example, the
      fraction of RNA polymerases that transcribe rRNA and tRNA drops from 80% during
      rapid growth to 24% within minutes of a sudden amino acid starvation. We recently
      reported in Nucleic Acids Research that the tRNA pool is more dynamically
      regulated than previously thought. In addition to the regulation at the level of
      synthesis, we found that tRNAs are subject to demand-based regulation at the
      level of their degradation. In this point-of-view article we address the question
      of why this phenomenon has not previously been described. We also present data
      that expands on the mechanism of tRNA degradation, and we discuss the possible
      implications of tRNA instability for the ability of E. coli to cope with stresses
      that affect the translation process.

PMID- 29023192
TI  - A Study on the Macroscopic Morphometry of the Lesion Area on Diabetic Ulcers in
      Humans Treated with Photodynamic Therapy Using Two Methods of Measurement.
AB  - BACKGROUND: Diabetes Mellitus is a chronic disease that can lead to lower-limb
      ulceration. The photodynamic therapy (PDT) is based on light interaction with a
      photosensitizer capable to promote bacterial death and acceleration of wound
      healing. OBJECTIVE: This study aims to accomplish a macroscopic morphometry
      evaluation on diabetic ulcer area in humans that were under PDT. MATERIALS AND
      METHODS: A clinical study was conducted by convenience sample, experimental,
      controlled, and blinded, composed of 12 patients of both sexes with diabetic
      ulcers in lower limbs that were divided into two groups, control (n = 6) and PDT
      (n = 6). They were all treated with collagenase/chloramphenicol during the
      experimental period, in which six of them had received PDT with Methylene Blue
      dye (0.01%) associated with laser therapy (660 nm, 30 mW, 8 sec, 6 J/cm2, beam
      area of 0.04 mm2), three times per week, totaling 10 sessions. Ulcer areas were
      analyzed by their nominal area and photographed for analysis through the
      ImageJ(r) software. Then, the Ulcer Healing Index and the wound area reduction
      were calculated for both groups. RESULTS: Data from the UHI and wound area
      reduction parameters show that there is a statistically significant difference (p
      < 0.05) between the control group and PDT group, with the PDT group showing a
      greater reduction of the diabetic ulcer area than the control group. In the
      ImageJ software area analysis, both patient groups presented significant
      differences (p < 0.05) between pre and post-treatment in relation to lesion
      reduction area, the PDT being better. CONCLUSIONS: Results show that PDT
      accelerates the closure of ulcer wounds and to evaluate the wound area, different
      measurement methods can be used to follow-up the tissue repair process.

PMID- 29023193
TI  - Distinct transcriptional and processing regulations control miR167a level in
      tomato during stress.
AB  - Besides their definite role in plant developmental processes miR167 also serve as
      mediator of stress response. Although differential expression of miR167 occurs
      during stresses, the regulatory-mechanism of biogenesis remained elusive.
      Therefore, using tomato as the model plant we have explored the mechanism of
      regulation of miR167a expression during stresses. Fungus or virus infections and
      exposure to cold stress raised the level of miR167a expression. Whereas, salt,
      drought and heat treatments resulted in the downregulation, indicating different
      stresses activated alternative mechanisms for miR167a regulation. Interestingly,
      the relative expression level of precursors in control versus temperature
      stressed plants differed from the pattern observed in the mature miR167a
      expression, suggesting that both transcriptional and processing regulation were
      important for biogenesis. The promoter-regulatory sequence of the major isoform
      MIR167a harbours several development and stress-related regulatory sites.
      Accordingly, promoter assays using transient transformation and transgenic
      tobacco plants proved stress-dependent regulation of the promoter. Further
      analyses corroborated the role of tomato DREB2A protein in the transcriptional
      regulation during temperature stress. Finally, in vitro assays established the
      importance of processing factors in cold-stress dependent efficient processing of
      MIR167a precursors. These data confirm distinct role of transcriptional and
      processing machinery in stress-influenced regulation of tomato miR167a
      biogenesis.

PMID- 29023194
TI  - Factors That Drive Youth Specialization.
AB  - BACKGROUND: Specialization in young athletes has been linked to overuse injuries,
      burnout, and decreased satisfaction. Despite continued opposition from the
      medical community, epidemiological studies suggest the frequency is increasing.
      HYPOTHESIS: Extrinsic pressures in addition to individual aspirations drive this
      national trend in sports specialization. STUDY DESIGN: Descriptive epidemiology
      study. LEVEL OF EVIDENCE: Level 3. METHODS: A novel instrument assessing the
      driving factors behind youth specialization was generated by an interdisciplinary
      team of medical professionals. Surveys were administered to patients and athletes
      in the department's sports medicine clinic. RESULTS: The survey was completed by
      235 athletes between 7 and 18 years of age, with a mean age of 13.8 +/- 3.0
      years. Athletes specialized at a mean age of 8.1 years, and 31% of athletes
      played a single sport while 58% played multiple sports but had a preferred sport.
      More than 70% of athletes had collegiate or professional ambitions, and 60%
      played their primary sport for 9 or more months per year, with players who had an
      injury history more likely to play year-round ( P < 0.01). Approximately one
      third of players reported being told by a coach not to participate in other
      sports, with specialized athletes reporting this significantly more often ( P =
      0.04). Half of the athletes reported that sports interfered with their academic
      performance, with older players stating this more frequently ( P < 0.01).
      CONCLUSION: Young athletes are increasingly specializing in a single sport before
      starting high school. While intrinsic drive may identify healthy aspirations,
      extrinsic influences are prevalent in specialized athletes. CLINICAL RELEVANCE:
      Extrinsic factors contributing to youth specialization were identified and
      compounded the deleterious sequelae of youth athlete specialization.

PMID- 29023195
TI  - Depth of Intestinal Wall Infiltration and Clinical Presentation of Deep
      Infiltrating Endometriosis: Evaluation of 553 Consecutive Cases.
AB  - INTRODUCTION: Intestinal involvement in endometriosis was first described by
      Sampson in 1922. The reported incidence ranges between 3% and 37% in patients
      diagnosed with endometriosis. In literature, there are few studies that correlate
      the severity of endometriosis (in terms of intestinal infiltration) and its
      clinical presentation. The aim of this study was to review the correlation
      between the severity of symptoms, the depth of intestinal wall infiltration, and
      lymph node involvement in our tertiary referral center. MATERIALS AND METHODS: We
      retrospectively analyzed 553 patients who had undergone intestinal resection for
      deep infiltrating endometriosis at our institution (Sacro Cuore Negrar Hospital)
      between 2004 and 2009. Based on intestinal wall infiltration, we divided patients
      into three groups (Group A: intestinal infiltration that reaches the muscle
      layer, Group B: infiltration to the submucosa, and Group C: endometriosis reaches
      the mucosa). Symptoms, intestinal stenosis, and positive lymph nodes were
      compared in the three groups with the chi-square test. RESULTS: No statistical
      correlation was found between symptoms and the intestinal wall infiltrations. The
      three groups were also compared on the basis of positive visceral lymph nodes and
      we did find a statistical difference (P = .05) in the lymph node count in the two
      main groups. CONCLUSION: There seems to be no statistically significant
      difference in symptoms between patients with different degrees of infiltration.
      Although visceral lymph node involvement has been occasionally described in
      literature, we found that it is related to submucosal infiltration.

PMID- 29023196
TI  - Home Parenteral Nutrition: Vascular Access and Related Complications.
AB  - Patients with chronic intestinal failure are dependent on parenteral nutrition
      (PN) to maintain health and preserve life. Maintaining safe vascular access is
      vital to prevent life-threatening complications such as catheter-related
      bloodstream infection or central venous occlusion. Dedicated central venous
      catheters with rigorous catheter care aseptic protocols are vital in obtaining
      good long-term outcomes that allow continuation of PN over many years. Good
      catheter care requires an experienced multidisciplinary team using appropriate
      vascular devices, trained to identify and aggressively treat catheter-related
      bloodstream infections, catheter occlusions, and catheter-related thrombosis.
      Consideration must also be given to evolving strategies to prevent recurrent
      infections, including prophylactic central venous catheter locks.

PMID- 29023198
TI  - Exploration of trauma, dissociation, maladaptive schemas and auditory
      hallucinations in a French sample.
AB  - OBJECTIVES: The main goal of the present study was to explore the associations
      between several key variables that have been shown to partially mediate the link
      between specific trauma exposure and auditory hallucinations (AH), that is,
      maladaptive schemas and dissociation in the general population. METHODS: In
      total, 425 voluntary participants were recruited from the general population and
      completed online the Childhood Trauma Questionnaire, the Young schema
      questionnaire, the Dissociative Experiences Scale, and the Launay-Slade
      Hallucination Scale. Data were analysed using Partial Least Squares Structural
      Equation Modelling. RESULTS: Our model showed that: (1) sexual and emotional
      abuse impact on AH both through the effect of maladaptive schemas and
      dissociation; (2) physical abuse impact on AH only through the effect of
      dissociation. More specifically, we found that four maladaptive schemas impact on
      AH: Abandonment, Vulnerability, Self-sacrifice and Subjugation. CONCLUSIONS:
      Overall, our findings indicate that specific early maladaptive schemas may play a
      fundamental role in the association between exposure to trauma and auditory
      hallucination together with dissociation symptoms in the general population.
      Consequently, our study suggest considering maladaptive schemas as an important
      therapeutic target when working with individuals experiencing AH with or without
      a psychiatry disorder.

PMID- 29023199
TI  - Responses of low and high compression during recovery after repeated sprint
      training in well-trained handball players.
AB  - The aim of the study was to investigate the effects of wearing various levels of
      compression following repeated and exhausting sprint exercise on variables
      related to recovery. Twelve well-trained handball players performed three
      sessions of repeated and exhausting sprint exercise (30 * 30m). Directly after
      each session the participants wore tights extending from below the hip to the
      foot with either 0, 10, or 25 mm Hg of compression onto the thigh and calf
      muscles. 48 h after the training session all participants performed 5 * 30m
      sprints and counter movement jumps. Before, directly after, 24 h, and 48 h after
      the training session venous blood samples were drawn for the determination of
      creatine kinase (CK), urea, C-reactive protein (CRP). At the same time points,
      subjective ratings of the Acute Recovery and Stress Scale (ARSS) questionnaires
      were obtained. The results for plasma concentrations of CK and urea showed
      'likely' to 'very, very likely' beneficial effects for compression garments
      exerting 10 mm Hg of compression (p = 0.06-1.0). With regard to sprint and jump
      performance no differences were evident between 0, 10, and 25 mm Hg (p = 0.07
      1.0). In addition, subjective scores from the ARSS did not differ between
      conditions over time (p > 0.05). We conclude that the application of 10 mm Hg leg
      compression compared to 0 and 25 mm Hg of compression during 48 h of recovery
      from repeated and exhausting sprints lowered the plasma concentrations of CK and
      urea with no improvements in recovery for performance.

PMID- 29023197
TI  - Mutational landscape of RNA-binding proteins in human cancers.
AB  - RNA Binding Proteins (RBPs) are a class of post-transcriptional regulatory
      molecules which are increasingly documented to be dysfunctional in cancer
      genomes. However, our current understanding of these alterations is limited.
      Here, we delineate the mutational landscape of ~1300 RBPs in ~6000 cancer
      genomes. Our analysis revealed that RBPs have an average of ~3 mutations per Mb
      across 26 cancer types. We identified 281 RBPs to be enriched for mutations
      (GEMs) in at least one cancer type. GEM RBPs were found to undergo frequent
      frameshift and inframe deletions as well as missense, nonsense and silent
      mutations when compared to those that are not enriched for mutations. Functional
      analysis of these RBPs revealed the enrichment of pathways associated with
      apoptosis, splicing and translation. Using the OncodriveFM framework, we also
      identified more than 200 candidate driver RBPs that were found to accumulate
      functionally impactful mutations in at least one cancer. Expression levels of 15%
      of these driver RBPs exhibited significant difference, when transcriptome groups
      with and without deleterious mutations were compared. Functional interaction
      network of the driver RBPs revealed the enrichment of spliceosomal machinery,
      suggesting a plausible mechanism for tumorogenesis while network analysis of the
      protein interactions between RBPs unambiguously revealed the higher degree,
      betweenness and closeness centrality for driver RBPs compared to non-drivers.
      Analysis to reveal cancer-specific Ribonucleoprotein (RNP) mutational hotspots
      showed extensive rewiring even among common drivers between cancer types.
      Knockdown experiments on pan-cancer drivers such as SF3B1 and PRPF8 in breast
      cancer cell lines, revealed cancer subtype specific functions like selective stem
      cell features, indicating a plausible means for RBPs to mediate cancer-specific
      phenotypes. Hence, this study would form a foundation to uncover the contribution
      of the mutational spectrum of RBPs in dysregulating the post-transcriptional
      regulatory networks in different cancer types.

PMID- 29023200
TI  - Gender Stereotype Activation versus Lexical Semantic Activation: An ERP Study.
AB  - It is an open question whether social stereotype activation can be distinguished
      from nonsocial semantic activation. To address this question, gender stereotype
      activation (GSA) and lexical semantic activation (LSA) were directly compared.
      EEGs were recorded in 20 participants as they identified the congruence between
      prime-target word pairs under four different conditions (stereotype congruent,
      stereotype incongruent, semantic congruent, and semantic incongruent). We found
      that congruent targets elicited faster and more accurate responses and reduced
      N400 amplitudes irrespective of priming category types. The N400 congruency
      effect (i.e., the difference between incongruity and congruity) started earlier
      and had greater amplitude for GSA than for LSA. Moreover, gender category priming
      induced a smaller N400 and a larger P600 than lexical category priming. These
      findings suggest that the brain is not only sensitive to both stereotype and
      semantic violation in the post-perceptual processing stage but can also
      differentiate these two information processes. Further, the findings suggest
      superior processing (i.e., faster and deeper processing) when the words are
      associated with social category and convey stereotype knowledge.

PMID- 29023201
TI  - Zebrafish Ride the Danube's Wave for the 10th European Zebrafish Meeting.

PMID- 29023202
TI  - Transplantation of Zebrafish Cells by Conventional Pneumatic Microinjector.
AB  - Generating chimeric zebrafish by transplantation is extremely useful for live
      imaging in developmental, stem cell, and cancer biology, and to answer the
      questions of how cells acquire, keep, and/or change their fate. However, as it is
      technically challenging, the use of transplantation approach remains very limited
      by the zebrafish community. In this study, we show that this cell grafting
      operation can be easily achieved by using a conventional pneumatic microinjector
      normally used for microinjections. Compared with previously published protocols,
      which need additional transplantation apparatus, this alternative transplantation
      method works well, but needs a simpler experimental setup, and is more accessible
      to all investigators.

PMID- 29023203
TI  - Examining Differences in Audience Recall and Reaction Between Mediated Portrayals
      of Mental Illness as Trivializing Versus Stigmatizing.
AB  - Researchers have documented the ways in which media stigmatize mental illness.
      However, media also portray mental illness trivially when diseases are mocked,
      oversimplified, shown to be less severe than in actuality, or represented as
      beneficial to an individual. Trivialization of mental illnesses could potentially
      lead audiences to be less likely to seek help or less likely to support related
      policy efforts. Therefore, it is important to understand how audiences recall and
      react to stigmatizing and trivializing mental illness portrayals. An experiment
      (N = 175) asked participants to recall either a media portrayal where mental
      illness was stigmatized or a portrayal where it was trivialized. Results suggest
      that audiences recall certain components of stigmatization and trivialization
      better than others. And, recollections of trivialization were associated with
      different patterns of word use than stigmatization. A second experiment (N = 141)
      found similar patterns when showing participants specific examples of different
      mental illness portrayals and asking them to immediately recall the content.
      Overall, these results suggest that theory and conceptual models about the nature
      and effects of mental illness portrayals could be updated to include both
      stigmatization and trivialization.

PMID- 29023204
TI  - Bury Your Gays and Social Media Fan Response: Television, LGBTQ Representation,
      and Communitarian Ethics.
AB  - Although visibility has increased, there are still television tropes used that
      can have potentially harmful effects on LGBTQ persons seeking identification
      through television characters. This essay explores the representation of women
      loving women (WLW) on television and how fans respond via social media with
      regard to their identity and representation. Specifically, by examining the fan
      culture through a communitarian ethics lens (with an emphasis on duty and
      mutuality), fans are explored before and after a lesbian character's death and
      how their responses created a social movement regarding the current television
      environment's treatment of WLW characters. Media anthropology and virtual
      ethnographic observations on Twitter and Tumblr were used to answer how fans were
      responding to WLW representation via social media and how they engaged with
      communitarian ethics. Implications and criticisms are discussed.

PMID- 29023205
TI  - The ethno-racial segmentation jobs: The impacts of the occupational stereotypes
      on hiring decisions.
AB  - This paper considers both the division of the labor market and the occupational
      stereotyping as explanatory mechanisms of discrimination in hiring decisions. It
      hypothesized that recruiters would favor candidates applying for a position that
      is stereotypically identified with their ethnic category. We solicited 146
      recruiters in order to evaluate the hireability of either a native-born or an
      immigrant candidate, either competent or not competent, for either a prestigious
      or a low-skill occupation, and to justify their decision in writing. As
      predicted, both the hireability ratings and the narrative comments produced by
      recruiters showed that native-born applicants were preferred for prestigious jobs
      while immigrants tended to be selected more often for low-skill positions.The
      discussion addresses various issues related to decision-making in recruitment
      settings.

PMID- 29023206
TI  - Out with .05, in with Replication and Measurement: Isolating and Working with the
      Particular Effect Sizes that are Troublesome for Inferential Statistics.
AB  - It is difficult to obtain adequate power to test a small effect size with a set
      criterion alpha of 0.05. Probably an inferential test will indicate non
      statistical significance and not be published. Rarely, statistical significance
      will be obtained, and an exaggerated effect size calculated and reported.
      Accepting all inferential probabilities and associated effect sizes could solve
      exaggeration problems. Graphs, generated through Monte Carlo methods, are
      presented to illustrate this. The first graph presents effect sizes (Cohen's d)
      as lines from 1 to 0 with probabilities on the Y axis and the number of measures
      on the X axis. This graph shows effect sizes of .5 or less should yield non
      significance with sample sizes below 120 measures. The other graphs show results
      with as many as 10 small sample size replications. There is a convergence of
      means with the effect size as sample size increases and measurement accuracy
      emerges.

PMID- 29023207
TI  - Sexual Orientation as a Peripheral Cue in Advertising: Effects of Models' Sexual
      Orientation, Argument Strength, and Involvement on Responses to Magazine Ads.
AB  - This study examines how sexual orientation of couples featured in magazine
      advertisements affects heterosexual viewers' responses using the elaboration
      likelihood model as a framework. A 3 * 2 * 2 * 3 experiment tested effects of
      sexual orientation, argument strength, involvement, and attitudes toward
      homosexuality on heterosexuals' attitudes toward the couple, advertisement,
      brand, and product, purchase intentions, and recall. Results indicate that
      consumers were accepting of ads with lesbian portrayals. Participants showed more
      negative attitudes toward gay male portrayals, but attitudes toward heterosexual
      and lesbian ads were similar. This effect was moderated by participants'
      attitudes toward homosexuals. Low-involvement consumers showed more negative
      attitudes toward homosexual portrayals than toward heterosexual portrayals,
      indicating that sexual orientation may have served as a peripheral cue negatively
      impacting attitudes toward the couple and ad under low elaboration. These effects
      were not observed for attitudes toward the brand and product, purchase
      intentions, or recall.

PMID- 29023208
TI  - Laboulbeniales parasitic on American small carrion beetles: new species of
      Corethromyces, Diphymyces, and Rodaucea.
AB  - Ten new species of Laboulbeniales parasitic on small carrion beetles (Coleoptera,
      Leiodidae, Cholevinae) from the American continent are described: Corethromyces
      bernardii on Dissochaetus spp. from Bolivia, Costa Rica, Ecuador, and the USA;
      Diphymyces anthracinus on Ptomaphagus brevior from the USA; D. blackwelliae on
      Ptomaphagus giaquintoi from Guatemala; D. costaricensis on Adelopsis sp. from
      Costa Rica; D. dichromus on Adelopsis marinae from Argentina; D. newtonii on
      Ptomaphagus fumosus from the USA; D. obesus on Ptomaphagus brevior from the USA;
      Diphymyces perreaui on Ptomaphagus nevadicus from the USA; D. polycarpus on
      Paulipalpina pillahuata from Peru; and Rodaucea hermanii on Adelopsis sp. from
      Costa Rica. The hosts for all 10 species have been retrieved from museum
      collections (1 was collected in the field as well). The following new combination
      is proposed: Rodaucea bruchii, bringing the number of species in the recently
      established genus Rodaucea to three.

PMID- 29023209
TI  - Age Differences In Emotion Recognition: Task Demands Or Perceptual
      Dedifferentiation?
AB  - : Background/Study Context: Older adults (OA) have consistently shown lower
      accuracy compared with younger adults (YA) when labeling facial expressions of
      emotion in multiple choice tasks. However, OA do not show lower accuracy when
      judging psychological attributes from faces in rating tasks. The authors
      investigated whether the cognitive demands of multiple choice tasks yields an
      underestimation of OA emotion recognition ability and whether lower scores by OA
      in emotion recognition tasks are an instance of age-related dedifferentiated face
      perception. METHODS: Younger and older adults judged the emotions of faces
      depicting various expressions using (a) a multiple choice task and (b) a rating
      task with separate scales for each expression. We computed both accuracy scores
      and an emotion differentiation index, adapted from previous work on neural
      activation to different stimulus categories. RESULTS: Lower OA performance in
      emotion recognition do not reflect the cognitive demands of a multiple choice
      task, since age differences also were shown when assessing emotion expressions on
      independent rating scales. An index calculating differentiation of the emotion
      expressions supported the hypothesis that age differences in emotion recognition
      accuracy may reflect age-related perceptual dedifferentiation. DISCUSSION:
      Results are consistent with other evidence for perceptual dedifferentiation in
      OA, including lower OA performance in face recognition tasks, rating faces more
      similarly to one another on trait dimensions, and less specificity in neural
      activation to faces.

PMID- 29023210
TI  - Free to be me: The relationship between the true self, rejection sensitivity, and
      use of online dating sites.
AB  - Prior research (Blackhart et al., 2014) found that rejection-sensitive
      individuals are more likely to use online dating sites. The purpose of the
      current research was to explain the relationship between rejection sensitivity
      and online dating site usage. Study 1 examined whether true self mediated the
      relation between rejection sensitivity and online dating. Study 2 sought to
      replicate the findings of Study 1 and to examine whether self-disclosure
      moderated the relationship between true self and online dating in the mediation
      model. Results replicated those found by Blackhart et al. and also found that
      true self mediated the relationship between rejection sensitivity and online
      dating site usage. These findings suggest that rejection-sensitive individuals
      feel they can more easily represent their "true" selves in online environments,
      such as online dating sites, which partially explains why they are more likely to
      engage in online dating.

PMID- 29023211
TI  - Factors influencing dietary fat intake among black emerging adults.
AB  - OBJECTIVE: To determine what factors influenced dietary fat intake (DFI) among
      black emerging adults. PARTICIPANTS: Sample included 251 black emerging adults,
      ages 18-25 years, living in the US. METHODS: This was a nonexperimental cross
      sectional study based on self-report data. RESULTS: The sample had high DFI.
      Factors related to DFI were gender (rpb = -.22, p < .001), perceived barriers for
      healthy eating (r = .32, p < .001), and perceived self-efficacy (r = -.33, p <
      .001). These variables were also significant predictors for DFI. Gender was
      significantly related to DFI (b = -5.894, p = .000). Religious commitment
      moderated the effect of stress on DFI. CONCLUSIONS: Gender, perceived barriers
      for healthy eating, and perceived self-efficacy were significant predictors for
      DFI. Religious commitment influenced the relationship of perceived stress and
      DFI. These findings may lead to interventions designed to reduce DFI and
      cardiovascular risks among black emerging adults.

PMID- 29023212
TI  - Pre-entry Characteristics, Perceived Social Support, Adjustment and Academic
      Achievement in First-Year Spanish University Students: A Path Model.
AB  - Transition to university is a multifactorial process to which scarce
      consideration has been given in Spain, despite this being one of the countries
      with the highest rates of academic failure and attrition within the European
      Union. The present study proposes an empirical model for predicting Spanish
      students' academic achievement at university by considering pre-entry
      characteristics, perceived social support and adaptation to university, in a
      sample of 300 traditional first-year university students. The findings of the
      path analysis showed that pre-university achievement and academic and personal
      emotional adjustment were direct predictors of academic achievement. Furthermore,
      gender, parents' education and family support were indirect predictors of
      academic achievement, mediated by pre-university grades and adjustment to
      university. The current findings supporting evidence that academic achievement in
      first-year Spanish students is the cumulative effect of pre-entry characteristics
      and process variables, key factors that should be taken into account in designing
      intervention strategies involving families and that establish stronger links
      between research findings and university policies.

PMID- 29023214
TI  - Reply to K. Lisy et al.

PMID- 29023213
TI  - Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small
      Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III
      Trials (CheckMate 017 and CheckMate 057).
AB  - Purpose Nivolumab, a programmed death-1 inhibitor, prolonged overall survival
      compared with docetaxel in two independent phase III studies in previously
      treated patients with advanced squamous (CheckMate 017; ClinicalTrials.gov
      identifier: NCT01642004) or nonsquamous (CheckMate 057; ClinicalTrials.gov
      identifier: NCT01673867) non-small-cell lung cancer (NSCLC). We report updated
      results, including a pooled analysis of the two studies. Methods Patients with
      stage IIIB/IV squamous (N = 272) or nonsquamous (N = 582) NSCLC and disease
      progression during or after prior platinum-based chemotherapy were randomly
      assigned 1:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3
      weeks). Minimum follow-up for survival was 24.2 months. Results Two-year overall
      survival rates with nivolumab versus docetaxel were 23% (95% CI, 16% to 30%)
      versus 8% (95% CI, 4% to 13%) in squamous NSCLC and 29% (95% CI, 24% to 34%)
      versus 16% (95% CI, 12% to 20%) in nonsquamous NSCLC; relative reductions in the
      risk of death with nivolumab versus docetaxel remained similar to those reported
      in the primary analyses. Durable responses were observed with nivolumab; 10 (37%)
      of 27 confirmed responders with squamous NSCLC and 19 (34%) of 56 with
      nonsquamous NSCLC had ongoing responses after 2 years' minimum follow-up. No
      patient in either docetaxel group had an ongoing response. In the pooled
      analysis, the relative reduction in the risk of death with nivolumab versus
      docetaxel was 28% (hazard ratio, 0.72; 95% CI, 0.62 to 0.84), and rates of
      treatment-related adverse events were lower with nivolumab than with docetaxel
      (any grade, 68% v 88%; grade 3 to 4, 10% v 55%). Conclusion Nivolumab provides
      long-term clinical benefit and a favorable tolerability profile compared with
      docetaxel in previously treated patients with advanced NSCLC.

PMID- 29023216
TI  - Provider Roles in Survivorship Care: Moving Beyond Surveys of Patient Preference.

PMID- 29023215
TI  - Cost-Effectiveness Analysis of Monthly Zoledronic Acid, Zoledronic Acid Every 3
      Months, and Monthly Denosumab in Women With Breast Cancer and Skeletal
      Metastases: CALGB 70604 (Alliance).
AB  - Purpose Skeletal-related events (SREs) such as pathologic fracture, spinal cord
      compression, or the necessity for radiation or surgery to bone metastasis cause
      considerable morbidity, decrements in quality of life, and costs to the health
      care system. The results of a recent large randomized trial (Cancer and Leukemia
      Group B/Alliance for Clinical Trials in Oncology [CALGB/Alliance 70604]) showed
      that zoledronic acid (ZA) every 3 months was noninferior to monthly ZA in
      reducing the risks of SREs. We sought to determine the cost-effectiveness (CE) of
      monthly ZA, ZA every 3 months, and monthly denosumab in women with breast cancer
      and skeletal metastases. Methods Using a Markov model, costs per SRE avoided were
      calculated for the three treatments. Sensitivity analyses were performed where
      denosumab SRE probabilities were assumed to be 50%, 75%, and 90% lower than the
      ZA SRE probabilities. Quality-adjusted life-years were also calculated. The
      analysis was from the US payer perspective. Results The mean costs of the
      denosumab treatment strategy are nine-fold higher than generic ZA every 3 months.
      Quality-adjusted life-years were virtually identical in all the three treatment
      arms; hence, the optimal treatment would be ZA every 3 months because it was the
      least costly treatment. The sensitivity analyses showed that relative to ZA every
      3 months, the incremental costs per mean SRE avoided for denosumab ranged from
      $162,918 to $347,655. Conclusion ZA every 3 months was more CE in reducing the
      risks of SRE than monthly denosumab. This analysis was one of the first to
      incorporate the costs of generic ZA and one of the first independent CE analyses
      not sponsored by either Novartis or Amgen, the makers of ZA and denosumab,
      respectively. ZA every 3 months is the more CE option and more reasonable
      alternative to monthly denosumab.

PMID- 29023217
TI  - Visual impairment by multiple vascular embolization with hydroxyapatite
      particles.
AB  - We demonstrate a case of ocular impairment caused by a hydroxyapatite filler
      injection and review the prior literature on clinical presentations. A healthy
      woman, who received a hydroxyapatite filler injection into the glabella for nose
      augmentation suddenly had symptoms of nausea, diplopia, visual loss in the left
      eye, and impaired consciousness. Her left eye showed paresis of the inferior
      branch of the oculomotor nerve, conjunctival injection, cell infiltration in the
      anterior chamber, and multiple white spots in the nasal fundus. Purpura was
      detected in the area from the glabella to the left forehead. An orbital computed
      tomography (CT) scan demonstrated high-density deposits along vessels in the left
      medial orbit and forehead. Although her consciousness stabilized after a few
      days, the vision in her left eye deteriorated due to corneal edema and both
      hypopyon and hyphema in the anterior chamber, and the skin from the glabella to
      the left forehead developed necrosis. Multiple plaques were observed within the
      conjunctival and scleral vessels. After 2 months, diplopia and visual loss issues
      were mostly resolved. A histological examination of the conjunctiva specimen
      showed multiple foreign bodies plugged vessels that could be dissolved by
      decalcification. Recently, the number of complications by cosmetic filler
      injections has increased. The migrated hydroxyapatite particles in vessels cause
      multiple vascular emboli that can lead to various symptoms.

PMID- 29023220
TI  - Photobiomodulation for Achilles Tendinopathy.

PMID- 29023219
TI  - Predictors of Outcome in Patients with Pediatric Intracerebral Hemorrhage:
      Development and Validation of a Modified Score.
AB  - Purpose To propose and validate a modified pediatric intracerebral hemorrhage
      (PICH) (mPICH) score and to compare its association with functional outcome to
      that of the original PICH score. Materials and Methods Data from prospectively
      included patients were retrospectively analyzed. Consecutive patients with
      nontraumatic PICH who had undergone clinical follow-up were included. The study
      population was divided into a development cohort (2008-2012, n = 100) and a
      validation cohort (2013-2016, n = 43). An mPICH score was developed after
      variables associated with poor outcome were identified at multivariate analysis
      (King's Outcome Scale for Childhood Head Injury score < 5a) in the development
      cohort. The accuracy of the score for prediction of poor outcome was evaluated
      (sensitivity, specificity). Discrimination and calibration of associations
      between the mPICH score and poor outcome cohorts were assessed (C statistics,
      Hosmer-Lemeshow test). Results The mPICH score assessed as follows: brain
      herniation, four points; altered mental status, three points; hydrocephalus, two
      points; infratentorial PICH, two points; intraventricular hemorrhage, one point;
      PICH volume greater than 2% of total brain volume, one point. An mPICH score
      greater than 5 was associated with severe disability or worse, with sensitivity
      of 97% (95% confidence interval [CI]: 83%, 100%) and specificity of 61% (95% CI:
      49%, 73%). The C statistic was 0.81 (95% CI: 0.73, 0.89). In the validation
      cohort, sensitivity and specificity were 95.2% (95% CI: 76%, 99%) and 77% (95%
      CI: 55%, 92%), respectively. There was no significant difference between the
      observed and predicted risks of poor outcome (P = .46). Conclusion An mPICH score
      was developed as a simple clinical and imaging grading scale for acute prognosis
      in patients with PICH. (c) RSNA, 2017.

PMID- 29023218
TI  - Out-of-Hospital Pediatric Patient Safety Events: Results of the CSI Chart Review.
AB  - OBJECTIVE: Studies of adult hospital patients have identified medical errors as a
      significant cause of morbidity and mortality. Little is known about the frequency
      and nature of pediatric patient safety events in the out-of-hospital setting. We
      sought to quantify pediatric patient safety events in EMS and identify patient,
      call, and care characteristics associated with potentially severe events.
      METHODS: As part of the Children's Safety Initiative -EMS, expert panels
      independently reviewed charts of pediatric critical ambulance transports in a
      metropolitan area over a three-year period. Regression models were used to
      identify factors associated with increased risk of potentially severe safety
      events. Patient safety events were categorized as: Unintended injury; Near miss;
      Suboptimal action; Error; or Management complication ("UNSEMs") and their
      severity and potential preventability were assessed. RESULTS: Overall, 265 of 378
      (70.1%) unique charts contained at least one UNSEM, including 146 (32.8%) errors
      and 199 (44.7%) suboptimal actions. Sixty-one UNSEMs were categorized as
      potentially severe (23.3% of UNSEMs) and nearly half (45.3%) were rated entirely
      preventable. Two factors were associated with heightened risk for a severe UNSEM:
      (1) age 29 days to 11 months (OR 3.3, 95% CI 1.25-8.68); (2) cases requiring
      resuscitation (OR 3.1, 95% CI 1.16-8.28). Severe UNSEMs were disproportionately
      higher among cardiopulmonary arrests (8.5% of cases, 34.4% of severe UNSEMs).
      CONCLUSIONS: During high-risk out-of-hospital care of pediatric patients, safety
      events are common, potentially severe, and largely preventable. Infants and those
      requiring resuscitation are important areas of focus to reduce out-of-hospital
      pediatric patient safety events.

PMID- 29023222
TI  - Erratum.

PMID- 29023221
TI  - Evaluation of the Effect of Phototherapy in Patients with Mandibular Fracture on
      Mandibular Dynamics, Pain, Edema, and Bite Force: A Pilot Study.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of phototherapy on
      bite force, facial swelling, mandibular movements, and pain in patients having
      undergone surgical treatment for mandibular fractures. BACKGROUND: These are
      among the predominant types of facial fractures, and treatment involving surgical
      fixation with titanium plates is one of the most common procedures in oral
      maxillofacial surgery. Phototherapy has been used to accelerate the muscle
      healing process and significantly improves muscle regeneration by inducing the
      formation of new muscle fibers. METHODS: The patients were divided into two
      groups: Group 1-active phototherapy, and Group 2-sham phototherapy. Both groups
      underwent the surgical procedure by the same surgeon using the same surgical
      technique. Dosimetric parameters are wavelength, 660 nm; power, 108 mW; radiant
      energy, 21.6 J; fluency, 21.6 J/cm2; radiance, 38197 mW/cm2; exposure time, 200
      sec per point, 10 points bilaterally. Photobiomodulation was performed in 15
      sessions. RESULTS: The primary variable was bite force measured with a
      gnathodynamometer and the secondary variables were facial swelling, mandibular
      movements (measured with digital calipers), and pain. The Student's t-test was
      used to determine intergroup differences. CONCLUSIONS: The findings suggest
      improvements in the laser group in comparison with the sham group with regard to
      mandibular dynamics, a reduction in postoperative facial swelling, a reduction in
      pain, and an increase in bite force.

PMID- 29023223
TI  - Point Prevalence and Patterns of Mental Health Comorbidity Among People Accessing
      Australia's First Older Adult-Specific Alcohol and Other Drug Treatment Service.
AB  - OBJECTIVE: There are good data regarding the prevalence and patterns of dual
      diagnosis among the general population; however, data regarding the older adult
      cohort are limited. We aimed to extend the knowledge of the point prevalence and
      patterns of dual diagnosis among older adults and the impact of dual diagnosis on
      the utilization of alcohol and other drug treatment services. METHOD: A 12-month
      medical chart audit of clients discharged from an Australian older adult-specific
      alcohol and other drug treatment service was performed. Measures included the
      Alcohol Use Disorders Identification Test-Consumption, the Drug Use Disorders
      Identification Test-Consumption, the Kessler 10, and the Modified MINI Screen.
      Additional data collected included mental health diagnoses, number of session
      types, and treatment outcomes. RESULTS: There were 79 (n = 45, 57% male) medical
      charts audited, with a mean age of 65.9 years (SD = 5.8). There were 68 (89%)
      clients having at least one comorbid mental illness. Clients with a dual
      diagnosis were younger (p = .011) than those without. Some comorbid mental health
      conditions were associated with additional service utilization (p < .05). Clients
      with personality disorders required more telephone calls and outreach services (p
      < .05). The number of mental health diagnoses was associated with additional
      treatment sessions (p < .05). CONCLUSIONS: Further research with a larger sample
      size of older adults seeking age-specific alcohol and other drug treatment
      services is required. Older adult-specific alcohol and other drug treatment
      services need to allow for longer episodes of care for clients with certain dual
      diagnoses and a focus on reducing anxiety to increase treatment retention.

PMID- 29023225
TI  - "Transformation Tuesday": Temporal context and post valence influence the
      provision of social support on social media.
AB  - Social network sites (SNSs) such as Facebook have become integral in the
      development and maintenance of interpersonal relationships. Users of SNSs seek
      social support and validation, often using posts that illustrate how they have
      changed over time. The purpose of the present research is to examine how the
      valence and temporal context of an SNS post affect the likelihood of other users
      providing social support. Participants viewed hypothetical SNS posts and reported
      their intentions to provide social support to the users. Results revealed that
      participants were more likely to provide social support for posts that were
      positive and included temporal context (i.e., depicted improvement over time;
      Study 1). Furthermore, this research suggests that visual representations of
      change over time are needed to elicit social support (Study 2). Results are
      discussed in terms of their practical implications for SNS users and theoretical
      implications for the literature on social support and social media.

PMID- 29023224
TI  - Zebrafish: A Premier Vertebrate Model for Biomedical Research in Indian Scenario.
AB  - The zebrafish (Danio rerio) is a versatile model organism that has been used in
      biomedical research for several decades to study a wide range of biological
      phenomena. There are many technical advantages of using zebrafish over other
      vertebrate models. They are readily available, hardy, easy, and inexpensive to
      maintain in the laboratory, have a short life cycle, and have excellent
      fecundity. Due to its optical clarity and reproducible capabilities, it has
      become one of the predominant models of human genetic diseases. Zebrafish
      research has made rapid strides in the United States and Europe, but in India the
      field is at an early stage and many researchers still remain unaware of the full
      research potential of this tiny fish. The zebrafish model system was introduced
      into India in the early 2000s. Up to now, more than 200 scientific referred
      articles have been published by Indian researchers. This review gives an overview
      of the current state of knowledge for zebrafish research in India, with the aim
      of promoting wider utilization of zebrafish for high level biological studies.

PMID- 29023226
TI  - Contrasting Evolutionary Paths Among Indo-Pacific Pomacentrus Species Promoted by
      Extensive Pericentric Inversions and Genome Organization of Repetitive Sequences.
AB  - Pomacentrus (damselfishes) is one of the most characteristic groups of fishes in
      the Indo-Pacific coral reef. Its 77 described species exhibit a complex taxonomy
      with cryptic lineages across their extensive distribution. Periods of
      evolutionary divergences between them are very variable, and the cytogenetic
      events that followed their evolutionary diversification are largely unknown. In
      this respect, analyses of chromosomal divergence, within a phylogenetic
      perspective, are particularly informative regarding karyoevolutionary trends. As
      such, we conducted conventional cytogenetic and cytogenomic analyses in four
      Pomacentrus species (Pomacentrus similis, Pomacentrus auriventris, Pomacentrus
      moluccensis, and Pomacentrus cuneatus), through the mapping of repetitive DNA
      classes and transposable elements, including 18S rDNA, 5S rDNA, (CA)15, (GA)15,
      (CAA)10, Rex6, and U2 snDNA as markers. P. auriventris and P. similis, belonging
      to the Pomacentrus coelestis complex, have indistinguishable karyotypes (2n = 48;
      NF = 48), with a peculiar syntenic organization of ribosomal genes. On the other
      hand, P. moluccensis and P. cuneatus, belonging to another clade, exhibit very
      different karyotypes (2n = 48, NF = 86 and 92, respectively), with a large number
      of bi-armed chromosomes, where multiple pericentric inversions played a
      significant role in their karyotype organization. In this sense, different
      chromosomal pathways followed the phyletic diversification in the Pomacentrus
      genus, making possible the characterization of two well-contrasting species
      groups regarding their karyotype features. Despite this, pericentric inversions
      act as an effective postzygotic barrier in many organisms, which appear to be
      also the case for P. moluccensis and P. cuneatus; the extensive chromosomal
      similarities in the two species of P. coelestis complex suggest minor
      participation of chromosomal postzygotic barriers in the phyletic diversification
      of these species.

PMID- 29023227
TI  - Humoral immune responses to select marine bacteria in loggerhead, Caretta
      caretta, and Kemp's ridley, Lepidochelys kempii, sea turtles from the south
      eastern United States.
AB  - Serum from Kemp's ridley and loggerhead sea turtles was collected in summers of
      2011, 2012, and 2013. Serum IgY recognition of lysate proteins from nine bacteria
      species and whole bacteria-specific IgY titers to these pathogens were
      quantified. Serum and purified IgY recognized proteins of all bacteria, with
      protein recognition in some species more pronounced than others. Circulating IgY
      titers against V. vulnificus, V. anguillarum, E. rhusiopathiae, and B.
      vesicularis changed over the years in Kemp's ridley turtles, while titers IgY
      against V. vulnificus, E. coli, V. parahaemolyticus, B. vesicularis, and M.
      marinum were different in loggerhead turtles. Serum lysozyme activity was
      constant for loggerhead turtles over the 3 years, while activity in Kemp's
      ridleys were lower in 2012 than 2013. Blood PCV, glucose levels, and serum
      protein levels were comparable to healthy turtles in previous studies, therefore,
      this study provides baseline information on antibody responses in healthy, wild
      turtles. Received 25 May 2017 accepted 09 Oct 2017 revised 15 Sep 2017.

PMID- 29023228
TI  - Preventing Chronic Disease: Progress and Achievement of 2017 Priorities.

PMID- 29023229
TI  - Shaping Future Generations of Public Health Researchers: Preventing Chronic
      Disease's Student Research Paper Contest.

PMID- 29023231
TI  - Marketing Strategies to Encourage Rural Residents of High-Obesity Counties to Buy
      Fruits and Vegetables in Grocery Stores.
AB  - INTRODUCTION: Obesity rates in Appalachia are among the highest in the United
      States, and knowledge of upstream approaches to decrease prevalence among this
      vulnerable population is limited. The primary aim of this study was to examine
      the association between healthy, diet-based, social marketing interventions in
      grocery stores and frequency of fruit and vegetable intake. METHODS: A social
      marketing campaign was conducted among 17 grocery stores (N = 240 participant
      surveys) over 4 months in 5 rural Kentucky counties. Interventions included
      providing food samples, recipe cards, and promotional discounts on fruits and
      vegetables and moving high-calorie foods to side aisles. RESULTS: Most survey
      participants reported that recipe cards influenced their desire to purchase
      ingredients as well as fruits and vegetables in general. Results indicated a
      significant association between the influence of recipe cards and frequency of
      fruit and vegetable consumption. CONCLUSION: Small-scale interventions in grocery
      stores influenced purchasing choices among Appalachian residents. Working with
      various store managers and food venues in rural high-obesity communities is a
      promising way to encourage purchasing of fruits and vegetables.

PMID- 29023230
TI  - A Diabetic Retinopathy Screening Tool for Low-Income Adults in Mexico.
AB  - INTRODUCTION: A national diabetic retinopathy screening program does not exist in
      Mexico as of 2017. Our objective was to develop a screening tool based on a
      predictive model for early detection of diabetic retinopathy in a low-income
      population. METHODS: We analyzed biochemical, clinical, anthropometric, and
      sociodemographic information from 1,000 adults with diabetes in low-income
      communities in Mexico (from 11,468 adults recruited in 2014-2016). A
      comprehensive ophthalmologic evaluation was performed. We developed the screening
      tool through the following stages: 1) development of a theoretical predictive
      model, 2) performance assessment and validation of the model using cross
      validation and the area under the receiver operating characteristic curve (AUC
      ROC), and 3) optimization of cut points for the classification of diabetic
      retinopathy. We identified points along the AUC ROC that minimized the
      misclassification cost function and considered various scenarios of
      misclassification costs and diabetic retinopathy prevalence. RESULTS: Time since
      diabetes diagnosis, high blood glucose levels, systolic hypertension, and
      physical inactivity were considered risk factors in our screening tool. The mean
      AUC ROC of our model was 0.780 (validation data set). The optimized cut point
      that best represented our study population (z = -0.640) had a sensitivity of
      82.9% and a specificity of 61.9%. CONCLUSION: We developed a low-cost and easy-to
      apply screening tool to detect people at high risk of diabetic retinopathy in
      Mexico. Although classification performance of our tool was acceptable (AUC ROC >
      0.75), error rates (precision) depend on false-negative and false-positive rates.
      Therefore, confirmatory assessment of all cases is mandatory.

PMID- 29023232
TI  - Early Onset Obesity and Risk of Metabolic Syndrome Among Chilean Adolescents.
AB  - INTRODUCTION: Obesity and metabolic syndrome (MetS) indicators have increased
      globally among the pediatric population. MetS indicators in the young elevate
      their risk of cardiovascular disease and metabolic disorders later in life. This
      study examined early onset obesity as a risk factor for MetS risk in adolescence.
      METHODS: A cohort of Chilean participants (N = 673) followed from infancy was
      assessed at age 5 years and in adolescence (mean age, 16.8 y). Adiposity was
      measured at both time points; blood pressure and fasting blood samples were
      assessed in adolescence only. Early onset obesity was defined as a World Health
      Organization z score of 2 standard deviations (SDs) or more for body mass index
      (BMI) at age 5 years. We used linear regression to examine the association
      between early onset obesity and adolescent MetS risk z score, adjusting for
      covariates. RESULTS: Eighteen percent of participants had early onset obesity,
      and 50% of these remained obese in adolescence. Mean MetS risk z score in
      adolescence was significantly higher among those with early onset obesity than
      among those without (1.0; SD, 0.8 vs 0.2; SD, 0.8 [P < .001]). In the
      multivariable model, early onset obesity independently contributed to a higher
      MetS risk score in adolescence (beta = 0.27, P < .001), controlling for obesity
      status at adolescence and sex, and explained 39% of the variance in MetS risk.
      CONCLUSION: Early onset obesity as young as age 5 years relates to higher MetS
      risk.

PMID- 29023233
TI  - Companeros: High School Students Mentor Middle School Students to Address Obesity
      Among Hispanic Adolescents.
AB  - INTRODUCTION: Promotoras, Hispanic community health workers, are frequently
      employed to promote health behavioral change with culturally bound Hispanic
      lifestyle behaviors. Peer health mentors have been used in schools to promote
      healthy nutrition and physical activity behaviors among students. This study
      investigates the efficacy of combining these 2 approaches by training high school
      health mentors, called companeros, to engage Hispanic middle school students in a
      school-based obesity intervention as a strategy to promote and sustain reductions
      in standardized body mass index (zBMI). METHODS: High school companeros were
      trained to participate in a 6-month obesity program alongside middle school
      students in Houston, Texas. Middle school students were randomized to participate
      in the program either with companeros (n = 94) or without companeros (n = 95).
      The intervention was conducted from 2013 through 2016 in 3 cohorts of students, 1
      each school year. Students were followed for 12 months. The primary outcome was
      zBMI, which was analyzed at baseline, 6 months, and 12 months. RESULTS:
      Significant differences were found between conditions across time (F = 4.58, P =
      .01). After the 6-month intervention, students in the condition with companeros
      had a larger decrease in zBMI (F = 6.94, P = .01) than students in the condition
      without companeros. Furthermore, students who received the intervention with
      companeros showed greater sustained results at 12 months (F = 7.65, P = .01).
      CONCLUSION: Using high school companeros in an obesity intervention for Hispanic
      middle school students could be effective in promoting and maintaining reductions
      in zBMI.

PMID- 29023234
TI  - Using Geographical Convergence of Obesity, Cardiovascular Disease, and Type 2
      Diabetes at the Neighborhood Level to Inform Policy and Practice.
AB  - INTRODUCTION: Chronic diseases are increasing across the world. Examination of
      local geographic variation in chronic disease patterns can enable policy makers
      to identify inequalities in health outcomes and tailor effective interventions to
      communities at higher risk. Our study aimed to determine the geographic variation
      of obesity, cardiovascular disease (CVD), and type 2 diabetes, using general
      practice clinical data. Further objectives included identifying regions of
      significantly high and low clusters of these conditions and assessing their
      association with sociodemographic characteristics. METHODS: A cross-sectional
      approach was used to determine the prevalence of obesity, CVD, and type 2
      diabetes in western Adelaide, Australia. The Getis-Ord Gi* method was used to
      identify significant hot spots of the conditions. Additionally, we used the
      Pearson correlation test to determine the association between disease clusters
      and risk factors, including socioeconomic status (SES), smoking history, and
      alcohol consumption. RESULTS: The spatial distribution of obesity, CVD, and type
      2 diabetes varied across communities. Hot spots of these conditions converged in
      3 locations across western Adelaide. An inverse relationship was observed between
      area-level prevalence of CVD, obesity, and type 2 diabetes with SES. CONCLUSION:
      Identification of significant disease clusters can help policy makers to target
      prevention strategies at the right people, in the right location. The approach
      taken in our study can be applied to identify clusters of other chronic diseases
      across the world, wherever researchers have access to clinical data.

PMID- 29023235
TI  - A Generally Efficient Targeted Minimum Loss Based Estimator based on the Highly
      Adaptive Lasso.
AB  - Suppose we observe n $n$ independent and identically distributed observations of
      a finite dimensional bounded random variable. This article is concerned with the
      construction of an efficient targeted minimum loss-based estimator (TMLE) of a
      pathwise differentiable target parameter of the data distribution based on a
      realistic statistical model. The only smoothness condition we will enforce on the
      statistical model is that the nuisance parameters of the data distribution that
      are needed to evaluate the canonical gradient of the pathwise derivative of the
      target parameter are multivariate real valued cadlag functions (right-continuous
      and left-hand limits, (G. Neuhaus. On weak convergence of stochastic processes
      with multidimensional time parameter. Ann Stat 1971;42:1285-1295.) and have a
      finite supremum and (sectional) variation norm. Each nuisance parameter is
      defined as a minimizer of the expectation of a loss function over over all
      functions it its parameter space. For each nuisance parameter, we propose a new
      minimum loss based estimator that minimizes the loss-specific empirical risk over
      the functions in its parameter space under the additional constraint that the
      variation norm of the function is bounded by a set constant. The constant is
      selected with cross-validation. We show such an MLE can be represented as the
      minimizer of the empirical risk over linear combinations of indicator basis
      functions under the constraint that the sum of the absolute value of the
      coefficients is bounded by the constant: i.e., the variation norm corresponds
      with this L1 $L_1$-norm of the vector of coefficients. We will refer to this
      estimator as the highly adaptive Lasso (HAL)-estimator. We prove that for all
      models the HAL-estimator converges to the true nuisance parameter value at a rate
      that is faster than n-1/4 $n^{-1/4}$ w.r.t. square-root of the loss-based
      dissimilarity. We also show that if this HAL-estimator is included in the library
      of an ensemble super-learner, then the super-learner will at minimal achieve the
      rate of convergence of the HAL, but, by previous results, it will actually be
      asymptotically equivalent with the oracle (i.e., in some sense best) estimator in
      the library. Subsequently, we establish that a one-step TMLE using such a super
      learner as initial estimator for each of the nuisance parameters is
      asymptotically efficient at any data generating distribution in the model, under
      weak structural conditions on the target parameter mapping and model and a strong
      positivity assumption (e.g., the canonical gradient is uniformly bounded). We
      demonstrate our general theorem by constructing such a one-step TMLE of the
      average causal effect in a nonparametric model, and establishing that it is
      asymptotically efficient.

PMID- 29023236
TI  - End-to-end workflow for finite element analysis of tumor treating fields in
      glioblastomas.
AB  - Tumor Treating Fields (TTFields) therapy is an approved modality of treatment for
      glioblastoma. Patient anatomy-based finite element analysis (FEA) has the
      potential to reveal not only how these fields affect tumor control but also how
      to improve efficacy. While the automated tools for segmentation speed up the
      generation of FEA models, multi-step manual corrections are required, including
      removal of disconnected voxels, incorporation of unsegmented structures and the
      addition of 36 electrodes plus gel layers matching the TTFields transducers.
      Existing approaches are also not scalable for the high throughput analysis of
      large patient volumes. A semi-automated workflow was developed to prepare FEA
      models for TTFields mapping in the human brain. Magnetic resonance imaging (MRI)
      pre-processing, segmentation, electrode and gel placement, and post-processing
      were all automated. The material properties of each tissue were applied to their
      corresponding mask in silico using COMSOL Multiphysics (COMSOL, Burlington, MA,
      USA). The fidelity of the segmentations with and without post-processing was
      compared against the full semi-automated segmentation workflow approach using
      Dice coefficient analysis. The average relative differences for the electric
      fields generated by COMSOL were calculated in addition to observed differences in
      electric field-volume histograms. Furthermore, the mesh file formats in MPHTXT
      and NASTRAN were also compared using the differences in the electric field-volume
      histogram. The Dice coefficient was less for auto-segmentation without versus
      auto-segmentation with post-processing, indicating convergence on a manually
      corrected model. An existent but marginal relative difference of electric field
      maps from models with manual correction versus those without was identified, and
      a clear advantage of using the NASTRAN mesh file format was found. The software
      and workflow outlined in this article may be used to accelerate the investigation
      of TTFields in glioblastoma patients by facilitating the creation of FEA models
      derived from patient MRI datasets.

PMID- 29023237
TI  - Corneal Tissue From Dry Eye Donors Leads to Enhanced Graft Rejection.
AB  - PURPOSE: To assess the effect of dry eye disease (DED) in graft donors on
      dendritic cell (DC) maturation, host T-cell sensitization, and corneal allograft
      rejection. METHODS: Corneas of control (healthy donor) and DED mice (C57BL/6)
      were transplanted onto fully allogeneic naive BALB/c recipients (n = 10
      mice/group). Long-term allograft survival was evaluated for 8 weeks. Corneas and
      draining lymph nodes (dLNs) were harvested at posttransplantation day 14 (n = 5
      mice/group). The frequencies of MHCII CD11c DCs in the donor corneas and host
      dLNs and the frequencies of interferon (IFN)-gamma and IL-17 CD4 T cells and
      Foxp3 expression by Tregs in host dLNs were investigated using flow cytometry.
      The enzyme-linked immunospot assay was used to assess host T-cell
      allosensitization through direct and indirect pathways (n = 3/group). RESULTS:
      Recipients of DED donor corneas showed significantly reduced graft survival (10%)
      compared with control mice (50% survival, P = 0.022), and had significantly
      increased frequencies of mature DCs in the grafted cornea (DED donor 44.0% +/-
      0.36% vs. healthy donor 35.4 +/- 0.5%; P < 0.0001) and host dLNs (DED donor 25.1%
      +/- 0.66% vs. healthy donor 13.7% +/- 1.6%; P = 0.005). Frequencies of IFN-gamma
      and IL-17 T cells were increased in the dLNs of recipients of DED corneas,
      whereas the expression (mean fluorescence intensity) of Foxp3 in Tregs was
      decreased significantly in these mice (DED donor 6004 +/- 193 vs. healthy donor
      6806 +/- 81; P = 0.0002). Enzyme-linked immunospot analysis showed that the
      direct pathway of allosensitization was significantly amplified in recipients of
      grafts with DED (P = 0.0146). CONCLUSIONS: Our results indicate that DED in the
      donor is a significant risk factor for subsequent corneal allograft rejection.

PMID- 29023238
TI  - Severe Phenotype of Keratitis-Ichthyosis-Deafness Syndrome With Presumed Ocular
      Surface Squamous Neoplasia.
AB  - PURPOSE: The aim of this study was to describe a case of severe keratitis
      ichthyosis-deafness (KID) syndrome with ocular surface squamous neoplasia.
      METHODS: The affected patient underwent complete ocular and systemic
      examinations. The molecular studies included polymerase chain reaction
      amplification and automated DNA sequencing of the complete gap junction beta-2
      (GJB2) gene coding sequence. RESULTS: A 30-year-old man presented with
      generalized erythro-hyperkeratosis and deafness and complaints of decreased
      visual acuity, tearing, and photophobia. Ophthalmic examination showed corneal
      erosion, vascularization, and a gray gelatinous lesion partially covering the
      right cornea, suggestive of squamous neoplasia. The clinical features were
      characteristic of KID syndrome. This diagnosis was confirmed with a DNA analysis
      showing the pathogenic variant p.D50N in the GJB2 gene. Presumed squamous
      neoplasia was treated with topical interferon alpha2b. CONCLUSIONS: KID syndrome
      is a very rare disease that has been reported with an incremental incidence of
      squamous cell carcinoma of the mucous membranes and skin (12%-15%). Here, we
      presented a case of severe systemic KID syndrome with ocular surface squamous
      neoplasia.

PMID- 29023239
TI  - Re: Generalizing Study Results: A Potential Outcomes Perspective.

PMID- 29023240
TI  - Correspondence Between Results and Aims of Funding Support in EPIDEMIOLOGY
      Articles.

PMID- 29023241
TI  - Estimating Causal Effects of Treatment in a Randomized Trial When Some
      Participants Only Partially Adhere.
AB  - The intention-to-treat analysis evaluates the causal effect of treatment
      assignment in a randomized controlled trial; however, participants do not always
      adhere to assigned treatment and the intention-to-treat effect may differ from
      the effect of treatment receipt. Although more recent adherence-based methods
      assess a well-defined causal effect of receiving treatment, adherence is assumed
      to be dichotomized as all or none. This approach can lack precision in the real
      world because adherence is a complex and heterogeneous phenomenon. In this
      article, we illustrate a simple method that provides estimates of bounds on the
      causal effect of full adherence to treatment in the presence of partial
      adherence. We first define three types of partial adherence (delayed, partial
      dose, posttreatment). We then use casual diagrams to show that categorizing
      partial adherence as nonadherence in a sensitivity analysis can lead to a
      violation of the exclusion restriction principle. Finally, we apply recently
      published sensitivity analyses related to principal stratification that allow for
      creating bound estimates around the causal effect of treatment in the presence of
      partial adherence.

PMID- 29023242
TI  - The Authors Respond.

PMID- 29023244
TI  - Integrating Training in Quality Improvement and Health Equity in Graduate Medical
      Education: Two Curricula for the Price of One.
AB  - A recent call to address health care disparities has come from the Accreditation
      Council for Graduate Medical Education's (ACGME's) Clinical Learning Environment
      Review (CLER) program. The CLER program aspires that faculty and residents will
      identify the disparities among the patient populations they serve and engage in
      quality improvement (QI) activities designed to address them. In this
      Perspective, the authors provide a framework for integrating QI and health equity
      principles in graduate medical education to meet these ACGME expectations. The
      authors illustrate their four-step framework by describing a faculty development
      workshop that provides strategies and tools for embedding equity into existing QI
      educational efforts and using QI methods to address equity challenges. Using
      examples, the authors outline how medical educators can begin to integrate QI and
      equity initiatives to address health care disparities and involve their
      residents/fellows in the process. In addition, the authors emphasize the
      importance of applying an equity lens to QI interventions and of recognizing that
      QI initiatives will have different impacts on outcomes depending on the patient
      population. The authors conclude by discussing the need for institutional
      leadership to build capacity and training to improve data collection and
      reporting of quality metrics by demographic variables; provide resources to
      disseminate lessons learned; support faculty development to teach and mentor
      trainees through equity-related QI work; and prioritize time in the curriculum
      for learners to participate in equity improvement activities.

PMID- 29023245
TI  - Education in Pediatrics Across the Continuum (EPAC): First Steps Toward Realizing
      the Dream of Competency-Based Education.
AB  - The Education in Pediatrics Across the Continuum (EPAC) Study Group is developing
      the first competency-based, time-variable progression from undergraduate medical
      education (UME) to graduate medical education (GME) in the history of medical
      education in the United States. EPAC, an innovation project sponsored by the
      Association of American Medical Colleges and supported by the Josiah Macy Jr.
      Foundation, was developed through a collaboration between five medical schools
      and multiple professional organizations with an interest in undergraduate and
      graduate medical education. The planning and implementation process demanded
      cooperatively addressing practical barriers such as education requirements for
      licensure and developing approaches to learner assessment that provided
      meaningful information about competency. Each participating school now has at
      least three cohorts of learners participating, and the program is transitioning
      its first cohort of students from UME to GME based on achievement of
      predetermined competencies that allow this transition. Members of the first
      cohort of learners in this program have begun their pediatric residency training
      at different times beginning in late 2016, confirming the feasibility of
      competency-based advancement from UME to GME in pediatrics. Although there is
      still much to learn about the outcomes of EPAC learners' professional development
      in residency training and beyond, EPAC has defined an operational approach to a
      different path through medical school and into residency training, based on the
      attainment of competence.

PMID- 29023243
TI  - Pediatric Auditory Brainstem Implantation: Surgical, Electrophysiologic, and
      Behavioral Outcomes.
AB  - OBJECTIVES: The objectives of this study were to demonstrate the safety of
      auditory brainstem implant (ABI) surgery and document the subsequent development
      of auditory and spoken language skills in children without neurofibromatosis type
      II (NFII). DESIGN: A prospective, single-subject observational study of ABI in
      children without NFII was undertaken at the University of North Carolina at
      Chapel Hill. Five children were enrolled under an investigational device
      exemption sponsored by the investigators. Over 3 years, patient demographics,
      medical/surgical findings, complications, device mapping, electrophysiologic
      measures, audiologic outcomes, and speech and language measures were collected.
      RESULTS: Five children without NFII have received ABIs to date without permanent
      medical sequelae, although 2 children required treatment after surgery for
      temporary complications. All children wear their device daily, and the benefits
      of sound awareness have developed slowly. Intra-and postoperative
      electrophysiologic measures augmented surgical placement and device programming.
      The slow development of audition skills precipitated limited changes in speech
      production but had little impact on growth in spoken language. CONCLUSIONS: ABI
      surgery is safe in young children without NFII. Benefits from device use develop
      slowly and include sound awareness and the use of pattern and timing aspects of
      sound. These skills may augment progress in speech production but progress in
      language development is dependent upon visual communication. Further monitoring
      of this cohort is needed to better delineate the benefits of this intervention in
      this patient population.

PMID- 29023246
TI  - Effect of various durations of smoking cessation on postoperative outcomes: A
      retrospective cohort analysis.
AB  - BACKGROUND: Preoperative smoking cessation is commonly advised in an effort to
      improve postoperative outcomes. However, it remains unclear for how long smoking
      cessation is necessary, and even whether a brief preoperative period of
      abstinence is helpful and well tolerated. OBJECTIVE: We evaluated associations
      between various periods of preoperative smoking cessation and major morbidity and
      death. DESIGN: Retrospective cohort analysis. SETTING: Adults who had noncardiac
      surgery at the Cleveland Clinic Main Campus between May 2007 and December 2013.
      PATIENTS: A total of 37 511 patients whose smoking history was identified from a
      preoperative Health Quest questionnaire. Of these patients, 26 269 (70%) were
      former smokers and 11 242 (30%) were current smokers. Of the current smokers,
      9482 (84%) were propensity matched with 9482 former smokers (36%). We excluded
      patients with American Society of Anesthesiologists' physical status exceeding
      four, patients who did not have general anaesthesia, and patients with missing
      outcomes and/or covariables. When multiple procedures were performed within the
      study period, only the first operation for each patient was included in the
      analysis. MAIN OUTCOME MEASURES: The relationship between smoking cessation and
      in-hospital morbidity/mortality. RESULTS: The incidence of the primary composite
      of in-hospital morbidity/mortality was 6.9% (656/9482) for all former smokers;
      the incidence was 7.8% (152/1951) for patients who stopped smoking less than 1
      year before surgery, 6.3% (118/1977) for 1 to 5 years, 7.2% (115/1596) for 5 to
      10 years and 6.9% (271/3457) for more than 10 years. CONCLUSION: Smoking
      cessation was associated with reduced in-hospital morbidity and mortality which
      was independent of cessation interval.

PMID- 29023247
TI  - miR-449a: a potential therapeutic agent for cancer.
AB  - MicroRNAs (miRNAs) have been reported to be associated with cancer progression
      and carcinogenesis. They are small, highly conserved, noncoding RNA molecules
      consisting of 19-25 nucleotides. By binding to complementary binding sites within
      the 3'-untranslated region of target mRNAs, miRNAs inhibit the translation of
      mRNAs or promote their degradation. miRNAs play critical roles in cancer
      initiation and development by functioning either as oncogenes or as tumor
      suppressors. Similarly, several studies have shown that miRNAs are involved in
      regulating various biological processes, including apoptosis, proliferation,
      cellular differentiation, signal transduction, and carcinogenesis. Among miRNAs,
      one that may be of particular interest in cancer biology is miR-449a, which has
      been reported to inhibit tumor growth, invasion, and metastasis, and to promote
      apoptosis and differentiation through the transforming growth factor-beta
      activated kinase 1, NOTCH, nuclear factor-kappaB/P65/vascular endothelial growth
      factor, retinoblastoma-E2F, mitogen-activated protein kinase signaling pathways,
      WNT-beta-catenin signaling, tumor protein P53, and androgen receptor signaling
      pathways. The miR-449 cluster is located in the second intron of CDC20B on
      chromosome 5q11.2, a region that has been identified as a susceptibility locus in
      cancer, and the abnormal expression of miR-449a may be related to the occurrence
      and development of tumors. As one example, miR-449a has been reported to be
      involved in the development of carcinoma and may be a potential prognostic
      indicator. On the basis of the putative pathogenetic relationships between cancer
      and miR-449a, we consider that miR-449a has the potential to serve as a
      therapeutic agent for the treatment of some types of cancer. In this review, the
      role of miR-449a in tumorigenesis and its mechanism of action are explored.
      Furthermore, its potential as a therapeutic agent in cancer treatment is
      considered.

PMID- 29023248
TI  - Anticancer effect of acid ceramidase inhibitor ceranib-2 in human breast cancer
      cell lines MCF-7, MDA MB-231 by the activation of SAPK/JNK, p38 MAPK apoptotic
      pathways, inhibition of the Akt pathway, downregulation of ERalpha.
AB  - Acid ceramidase is the key enzyme of the ceramide metabolic pathway, which plays
      a vital role in regulating ceramide - sphingosine-1-phosphate rheostat. Ceramide
      acts as a proapoptotic molecule, but its metabolite sphingosine-1-phosphate, in
      contrast, signals for cell proliferation, cell survival, and angiogenesis. Acid
      ceramidase is highly upregulated in breast tumors and treatment with an acid
      ceramidase inhibitor, ceranib-2, significantly induced apoptosis in human breast
      cancer cell lines. However, the mechanisms underlying the induction of apoptosis
      remain ambiguous to date. Hence, in the present study, we have explored ceranib-2
      mediated apoptotic signaling pathways in human breast cancer cell lines. MCF-7
      and MDA MB-231 cells were treated with IC50 doses of ceranib-2 and tamoxifen.
      Nuclear changes showed the apoptotic effect of ceranib-2 in both the cell lines.
      Loss in the mitochondrial membrane potential was observed only in ceranib-2
      treated MCF-7 cells. Ceranib-2 activated intrinsic and extrinsic apoptotic
      pathways in MCF-7 cells, but only the extrinsic apoptotic pathway was activated
      in MDA MB-231 cells. Further, ceranib-2 induced apoptosis by activating SAPK/JNK
      (stress-activated protein kinase/c-Jun N-terminal kinase), p38 MAPK (mitogen
      activated protein kinase) apoptotic pathways and by inhibiting the Akt
      (antiapoptotic) pathway in both the cell lines. Most importantly, ERalpha
      (estrogen receptor-alpha) expression was highly downregulated after ceranib-2
      treatment and a docking study predicted the highest binding affinity of ceranib-2
      than tamoxifen with ERalpha in MCF-7 cells. Hence, ceranib-2 may have potential
      as a chemotherapeutic drug of breast cancer.

PMID- 29023249
TI  - Priming With 1-Hz Repetitive Transcranial Magnetic Stimulation Over
      Contralesional Leg Motor Cortex Does Not Increase the Rate of Regaining
      Ambulation Within 3 Months of Stroke: A Randomized Controlled Trial.
AB  - BACKGROUND: The potential benefits of repetitive transcranial magnetic
      stimulation (rTMS), applied either alone or as a combination treatment, on
      recovery of lower limbs after stroke have been insufficiently studied. OBJECTIVE:
      The aim of the study was to evaluate the effect of priming with 1-Hz repetitive
      transcranial magnetic stimulation over contralesional leg motor area with a
      double-cone coil before physical therapy on regaining ambulation. METHODS: Thirty
      eight subacute stroke patients with significant leg disabilities were randomly
      assigned into the experimental group or control group to receive a 15-min real or
      sham 1-Hz repetitive transcranial magnetic stimulation, respectively, over the
      contralesional motor cortex representing the quadriceps muscle followed by 45-min
      physical therapy for 15 sessions for 3 wks. Functional measures, motor evoked
      potentials, and quality of life were assessed. RESULTS: There was no significant
      difference between experimental group and control group regarding the recovery in
      ambulation, balance, motor functions, and activity of daily living. No
      significant difference was found in other functional measures and the quality of
      life. Only the control group displayed significantly increased cortical
      excitability of the contralesional hemisphere after the intervention.
      CONCLUSIONS: The present study found that insufficient evidence that
      contralesional priming with 1-Hz repetitive transcranial magnetic stimulation
      improves ambulatory and other motor functions among patients with a severe leg
      dysfunction in subacute stroke.

PMID- 29023250
TI  - Biomechanical Determinants of Right Ventricular Failure in Pulmonary
      Hypertension.
AB  - Pulmonary hypertension (PH) is a disease characterized by progressive adverse
      remodeling of the distal pulmonary arteries, resulting in elevated pulmonary
      vascular resistance and load pressure on the right ventricle (RV), ultimately
      leading to RV failure. Invasive hemodynamic testing is the gold standard for
      diagnosing PH and guiding patient therapy. We hypothesized that lumped-parameter
      and biventricular finite-element (FE) modeling may lead to noninvasive
      predictions of both PH-related hemodynamic and biomechanical parameters that
      induce PH. We created patient-specific biventricular FE models that characterize
      the biomechanical response of the heart and coupled them with a lumped-parameter
      model that represents the systemic and pulmonic circulation. Simulations were
      calibrated by adjusting the pulmonary vascular resistance and myocardial
      contractility parameters through matching imaging data of ventricular chambers.
      Linear regression analysis demonstrated that the lumped-derived RV cardiac index
      (CI) was in good agreement with catheterization measurements collected from 10
      patients with PH (R = 0.82; p < 0.001). Biventricular FE analysis revealed a
      paradoxical leftward shift of the interventricular septum, and this correlated
      with invasive measurements of pulmonary vascular resistances (R = 0.70; p =
      0.048) as found by Pearson's coefficient. A significant difference was noted for
      RV myocardial fiber stress in healthy control patients (4.5 +/- 0.7 kPa) compared
      with that of patients with PH at either rest (30.1 +/- 12.1 kPa; p = 0.005) or
      simulated exercise conditions (69.6 +/- 24.8 kPa; p < 0.001), thus suggesting
      adverse RV remodeling. This approach may become a useful and versatile tool for
      noninvasively assessing RV impairment induced by PH and realistically predicting
      ventricular mechanics and interactions for an improved management of patients
      with PH.

PMID- 29023251
TI  - Programmatic Evaluation of an Algorithm for Intensified Tuberculosis Case Finding
      and Isoniazid Preventive Therapy for People Living With HIV in Thailand and
      Vietnam.
AB  - BACKGROUND: Tuberculosis (TB) screening affords clinicians the opportunity to
      diagnose or exclude TB disease and initiate isoniazid preventive therapy (IPT)
      for people living with HIV (PLHIV). METHODS: We implemented an algorithm to
      diagnose or rule out TB among PLHIV in 11 HIV clinics in Thailand and Vietnam. We
      assessed algorithm yield and uptake of IPT and factors associated with TB disease
      among PLHIV. RESULTS: A total of 1448 PLHIV not yet on antiretroviral therapy
      (ART) were enrolled and screened for TB. Overall, 634 (44%) screened positive and
      119 (8%) were diagnosed with TB; of these, 40% (48/119) were diagnosed by a
      positive culture following a negative sputum smear microscopy. In total, 55% of
      those eligible (263/477) started on IPT and of those, 75% (196/263) completed
      therapy. The prevalence of TB disease we observed in this study was 8.2% (8218
      per 100,000 persons): 46 and 25 times the prevalence of TB in the general
      population in Thailand and Vietnam, respectively. Several factors were
      independently associated with TB disease including being underweight [aOR (95%
      CI): 2.3 (1.2 to 2.6)] and using injection drugs [aOR (95% CI): 2.9 (1.3 to
      6.3)]. CONCLUSIONS: The high yield of TB disease diagnosed among PLHIV screened
      with the algorithm, and higher burden among PLHIV who inject drugs, underscores
      the need for innovative, tailored approaches to TB screening and prevention. As
      countries adopt test-and-start for antiretroviral therapy, TB screening,
      sensitive TB diagnostics, and IPT should be included in differentiated-care
      models for HIV to improve diagnosis and prevention of TB among PLHIV.

PMID- 29023253
TI  - Looking Back and Looking Forward Through the Lens of the Nursing Professional
      Development: Scope and Standards of Practice, 3rd Edition.
AB  - This final column in the Nursing Professional Development (NPD) Scope and
      Standards department provides five exemplars of incorporation of the scope and
      standards into NPD practice and ends with a call to action for all NPD
      practitioners.

PMID- 29023252
TI  - Partner Notification for Youth Living With HIV in 14 Cities in the United States.
AB  - BACKGROUND: Identifying factors associated with partner notification among youth
      living with HIV is critical for effective HIV prevention and treatment
      strategies. METHODS: A total of 924 male and female behaviorally infected youth
      aged 13-24 across 14 U.S. cities completed an audio computer-assisted self
      interview including questions about demographics and experiences with patient-
      and provider-referral partner notification. RESULTS: The majority of participants
      self-identified as male (82.5%), Black/non-Hispanic (70.1%), and Hispanic/Latino
      (18.2%). Most males (93.4%) reported engaging in male-to-male sexual contact.
      Over three-quarters (77.6%) reported that all or some of their partners were
      contacted, while 22.4% indicated that none were contacted regarding potential HIV
      exposure. Most (52.4%) reported that only one person talked to them about
      notifying partners including the HIV tester (36.5%) followed by their health care
      provider/doctor (27.6%). Less than a fifth (18.3%) were themselves notified of
      their own exposure to HIV. Using multivariable logistic regression, 3 factors
      were associated with successful partner notification: (1) when more than one
      person talked to participants about partner notification (AOR = 1.87, 1.33-2.62);
      (2) if they themselves had been notified of their own HIV exposure (AOR = 1.83,
      1.13-2.95); and (3) if their education included some college or technical school
      versus less than high school (AOR = 1.72, 1.04-2.85). CONCLUSIONS: Partner
      notification among youth living with HIV is unsuccessful at least 22.4% of the
      time, although minimal criteria for partner services are being met almost
      universally. Partner notification might benefit from enhanced guidelines that
      call for both HIV testers and HIV care providers to discuss this important
      strategy with HIV-positive youth.

PMID- 29023254
TI  - The Lived Experience of Gynecologic Cancer Survivors in Taiwan.
AB  - BACKGROUND: Although it is now possible to achieve permanent remission in a large
      percentage of gynecologic cancer (GC) cases, many GC patients in remission
      experience side effects or complications that influence their physical function
      and family relationships. Compared with other types of cancer patients, survivors
      of GC face greater challenges in terms of physical and psychological adaptations,
      and many of these do not receive sufficient assistance. An in-depth understanding
      of the lived experiences and demands of GC survivors is key to constructing
      comprehensive related healthcare services. PURPOSE: The aim of this study was to
      understand the lived experience of GC survivors in Taiwan to help their return to
      a healthy life. METHODS: This was a phenomenological study. Twenty-three
      survivors of GC participated in semistructured interviews that were held in a
      private environment. The transcripts were based on synchronous recordings from
      the interviews. Giorgi's phenomenology analysis was adopted for data analysis.
      RESULTS: Three themes with six subthemes were extracted from the data, including
      (a) the inner struggle of living with cancer and recurrence: repeatedly exploring
      the causes of cancer and treatment and facing a fear of cancer recurrence, (b)
      the interpretation and adjustment to cancer treatment: filled with fluctuating
      physical and mental distress and working to adopt a different perspective, and
      (c) the long passage of finding a desirable lifestyle: adjusting to long-term
      coexistence with side effects and realizing the strength of society, body, and
      mind. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The journey of rehabilitation for GC
      survivors is very long. The participants in this study faced different respective
      challenges during the diagnosis, treatment, and adjustment phases. Conventional
      disease-oriented medical care cannot satisfy the requirements of cancer patients
      because of patient-decentralized services. Our results indicate that GC survivors
      face diverse problems, both physically and mentally. Healthcare professionals
      should work to facilitate the psychological adjustment of cancer survivors and
      provide timely professional advice in combination with social resources. These
      results may serve as a reference for cancer care professionals who are navigating
      healthcare services.

PMID- 29023255
TI  - Adolescent Perceptions of Peer Responses to Diabetes Self-Management: A
      Qualitative Study.
AB  - BACKGROUND: Type 1 diabetes (T1D) is more prevalent in adolescents than in
      adults, and the self-management of insulin-dependent diabetes is complex. T1D
      requires injections of insulin, self-management of blood testing, regular
      physical activity, and diet monitoring, which are challenging for growing and
      developing adolescents. Adolescents are often more concerned with how they are
      perceived by their peers than how they perceive themselves. Positive peer
      responses influence the self-care management of adolescents with T1D in school
      settings. By contrast, negative peer responses and avoidance behaviors threaten
      to negatively affect the health outcomes of adolescents with T1D. Evidence
      indicates that peer influence is crucial to the successful self-management of
      diabetes in adolescents. However, very few studies have investigated the effect
      of peer influence on adolescents with T1D. PURPOSE: This article describes how
      adolescents with T1D perceive the responses of their peers to their diabetes self
      management in school settings. METHODS: Ten 12- to 17-year-old adolescents with
      diabetes were recruited from a pediatric endocrinology clinic at a university
      hospital in Taiwan. Audio-recorded interview data were transcribed verbatim and
      reviewed for accuracy. A thematic analysis approach was used to analyze the
      narrative content of semistructured interviews with participants. The rigor of
      the data collection and analysis was emphasized. RESULTS: Analysis of peer
      responses to the diabetes care practices of the participants revealed six themes:
      knowledge seeking, curiosity, enthusiasm, empathy, fearfulness, and isolation and
      bullying. Subthemes were categorized to illustrate how adolescents with T1D
      balance the challenge of diabetes self-care regimens and normal peer
      interactions. They were coping with the requirements of their T1D regimen and
      hoping to determine the perceptions of their peers toward this regimen and
      themselves. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Understanding the perception
      of peer identity for adolescents with T1D provides information for diabetes
      education and assists school nurses to facilitate successful T1D management in
      adolescents.

PMID- 29023256
TI  - The Boreds.

PMID- 29023258
TI  - Commentary to LTE Fetterolf and Koob.

PMID- 29023257
TI  - Impact of Abdominal Lipectomy on Post-Sleeve Gastrectomy Surgery Weight Loss.
AB  - BACKGROUND: Abdominal lipectomy after bariatric surgery is recommended because of
      residual excess skin resulting in difficulty with maintaining hygiene, recurrent
      infections, and functional impairment, interfering with daily activities. There
      is a dearth of literature examining weight loss outcomes in patients undergoing
      abdominal lipectomy post sleeve gastrectomy (SG). The purpose of this study was
      to examine whether post-SG patients who received abdominal lipectomy achieved
      greater percent excess weight loss (%EWL) than post-SG patients who did not
      receive abdominal lipectomy. METHODS: Retrospective study of patients who
      underwent minimally invasive SG at the University of Illinois Hospital and Health
      Sciences System from March 2008 to June 2015 was conducted. The cohort was
      divided into 2 groups: patients who underwent abdominal lipectomy after SG (PS
      SG) and patients who underwent SG alone (SG). Demographics, comorbidities, and
      %EWL were examined. RESULTS: Twenty-nine patients were included in the PS-SG
      group versus 287 patients in the SG group. Significant differences were found in
      %EWL at 24 (P < 0.0001), 36 (P < 0.005), and more than 36 months (P < 0.005)
      follow-up between groups, with a greater %EWL in patients in the PS-SG group
      versus the SG group. CONCLUSIONS: This preliminary study revealed that patients
      in the PS-SG group achieved greater %EWL than patients with SG alone. Although
      larger studies are needed, this study supports using abdominal lipectomy as an
      adjunctive procedure to assist with long-term weight loss as part of the overall
      treatment of bariatric surgery patients.

PMID- 29023259
TI  - Personal and Professional Characteristics of U.S. Dual-Boarded Critical Care
      Cardiologists in 2015.
AB  - OBJECTIVES: Evaluate the characteristics of U.S. physicians who are board
      certified in cardiology and critical care medicine ("dual-boarded
      cardiologists"). DESIGN: Retrospective cross-sectional study using a
      comprehensive database of licensed U.S. physicians linked to Medicare claims.
      SETTING: The United States. SUBJECTS: Dual-boarded cardiologists. MEASUREMENTS
      AND MAIN RESULTS: We used a comprehensive physician database to identify all
      physicians who were board certified in cardiology and critical care medicine
      before July 2015. We assessed physicians' characteristics and compared dual
      boarded cardiologists with and without active board certification in critical
      care medicine and estimated the maximum proportion of 2014 Medicare Cardiac ICU
      admissions treated by dual-boarded cardiologists. Among 473 dual-boarded
      cardiologists, 16 (3.4%) were women; 468 (99%) and 85 (18%) maintained active
      board certification in cardiology and critical care medicine, respectively.
      Overall, 98 dual-boarded cardiologists (21%) submitted 1,215 total claims for
      critical care services in 2014. Compared to dual-boarded cardiologists without
      active board certification in critical care medicine, those with active
      certification had more publications (median publications: 6.5 vs 3.0; p = 0.002),
      were more likely to be professors (22.3% vs 9.5%; p = 0.003), and were more
      likely to bill Medicare for critical care services (29% vs 17.8%; p = 0.002). We
      estimated that no more than 0.47% of all 2014 Medicare Cardiac ICU admissions
      were treated by a dual-boarded cardiologist. CONCLUSIONS: Dual-boarded
      cardiologists appear to deliver a small proportion of all Cardiac ICU services
      received by Medicare beneficiaries. Optimizing the modern Cardiac ICU workforce
      will require greater efforts to promote and support the training of dual-boarded
      cardiologists.

PMID- 29023260
TI  - Dysphagia in Mechanically Ventilated ICU Patients (DYnAMICS): A Prospective
      Observational Trial.
AB  - OBJECTIVES: Swallowing disorders may be associated with adverse clinical outcomes
      in patients following invasive mechanical ventilation. We investigated the
      incidence of dysphagia, its time course, and association with clinically relevant
      outcomes in extubated critically ill patients. DESIGN: Prospective observational
      trial with systematic dysphagia screening and follow-up until 90 days or death.
      SETTINGS: ICU of a tertiary care academic center. PATIENTS: One thousand three
      hundred four admissions of mixed adult ICU patients (median age, 66.0 yr
      [interquartile range, 54.0-74.0]; Acute Physiology and Chronic Health Evaluation
      II score, 19.0 [interquartile range, 14.0-24.0]) were screened for postextubation
      dysphagia. Primary ICU admissions (n = 933) were analyzed and followed up until
      90 days or death. Patients from an independent academic center served as
      confirmatory cohort (n = 220). INTERVENTIONS: Bedside screening for dysphagia was
      performed within 3 hours after extubation by trained ICU nurses. Positive
      screening triggered confirmatory specialist bedside swallowing examinations and
      follow-up until hospital discharge. MEASUREMENTS AND MAIN RESULTS: Dysphagia
      screening was positive in 12.4% (n = 116/933) after extubation (18.3% of
      emergency and 4.9% of elective patients) and confirmed by specialists within 24
      hours from positive screening in 87.3% (n = 96/110, n = 6 missing data). The
      dysphagia incidence at ICU discharge was 10.3% (n = 96/933) of which 60.4% (n =
      58/96) remained positive until hospital discharge. Days on feeding tube, length
      of mechanical ventilation and ICU/hospital stay, and hospital mortality were
      higher in patients with dysphagia (all p < 0.001). The univariate hazard ratio
      for 90-day mortality for dysphagia was 3.74 (95% CI, 2.01-6.95; p < 0.001). After
      adjustment for disease severity and length of mechanical ventilation, dysphagia
      remained an independent predictor for 28-day and 90-day mortality (excess 90-d
      mortality 9.2%). CONCLUSIONS: Dysphagia after extubation was common in ICU
      patients, sustained until hospital discharge in the majority of affected
      patients, and was an independent predictor of death. Dysphagia after mechanical
      ventilation may be an overlooked problem. Studies on underlying causes and
      therapeutic interventions seem warranted.

PMID- 29023262
TI  - Psychometric Properties and Factor Structure of a Long and Shortened Version of
      the Cognitive and Behavioural Responses Questionnaire.
AB  - OBJECTIVE: Symptoms of chronic fatigue syndrome (CFS) can be perpetuated by
      cognitive and behavioral responses to the illness. We aimed to determine the
      factor structure, reliability, and validity of the 40-item Cognitive and
      Behavioural Responses Questionnaire (CBRQ) using data gathered from CFS patients.
      We also propose a short-version CBRQ for greater clinical utility. METHODS: The
      psychometric analysis was performed on data sets drawn from two sources: a
      clinical service for CFS patients (n = 576) and the PACE randomized controlled
      trial of CFS treatments (n = 640). An exploratory factor analysis was conducted
      on the clinical data set and a confirmatory factor analysis was performed on the
      randomized controlled trial data set. Using these results, a short version of the
      CBRQ was proposed. Reliability, metric invariance across age and sex, and
      construct validity were assessed. RESULTS: The exploratory factor analysis
      (relative chi = 2.52, root mean square error of approximation = 0.051,
      comparative fit index = 0.964, Taylor-Lewis Index = 0.942) and confirmatory
      factor analysis (relative chi = 4.029, root mean square error of approximation =
      0.069, comparative fit index = 0.901, Taylor-Lewis Index = 0.892) revealed that
      eight-factor models fitted the data well. Satisfactory Cronbach's alpha values
      were obtained for the final subscales (>=0.76). The shortened CBRQ was obtained
      by removing items that cross-loaded onto other factors and/or were the lowest
      loading items in each factor. The shortened CBRQ contained 18 items that had high
      factor loadings, good face validity, and reliability (Cronbach's alpha = 0.67
      0.88). CONCLUSIONS: The CBRQs, long and short versions, are reliable and valid
      scales for measuring cognitive and behavioral responses of patients with CFS.
      Further research is needed to examine the utility of the CBRQ in other long-term
      conditions.

PMID- 29023261
TI  - Prevention of Ventilator-Associated Pneumonia: The Multimodal Approach of the
      Spanish ICU "Pneumonia Zero" Program.
AB  - OBJECTIVES: The "Pneumonia Zero" project is a nationwide multimodal intervention
      based on the simultaneous implementation of a comprehensive evidence-based bundle
      measures to prevent ventilator-associated pneumonia in critically ill patients
      admitted to the ICU. DESIGN: Prospective, interventional, and multicenter study.
      SETTING: A total of 181 ICUs throughout Spain. PATIENTS: All patients admitted
      for more than 24 hours to the participating ICUs between April 1, 2011, and
      December 31, 2012. INTERVENTION: Ten ventilator-associated pneumonia prevention
      measures were implemented (seven were mandatory and three highly recommended).
      The database of the National ICU-Acquired Infections Surveillance Study (Estudio
      Nacional de Vigilancia de Infecciones Nosocomiales [ENVIN]) was used for data
      collection. Ventilator-associated pneumonia rate was expressed as incidence
      density per 1,000 ventilator days. Ventilator-associated pneumonia rates from the
      incorporation of the ICUs to the project, every 3 months, were compared with data
      of the ENVIN registry (April-June 2010) as the baseline period. Ventilator
      associated pneumonia rates were adjusted by characteristics of the hospital,
      including size, type (public or private), and teaching (postgraduate) or
      university-affiliated (undergraduate) status. MEASUREMENTS AND MAIN RESULTS: The
      181 participating ICUs accounted for 75% of all ICUs in Spain. In a total of
      171,237 ICU admissions, an artificial airway was present on 505,802 days (50.0%
      of days of stay in the ICU). A total of 3,474 ventilator-associated pneumonia
      episodes were diagnosed in 3,186 patients. The adjusted ventilator-associated
      pneumonia incidence density rate decreased from 9.83 (95% CI, 8.42-11.48) per
      1,000 ventilator days in the baseline period to 4.34 (95% CI, 3.22-5.84) after 19
      21 months of participation. CONCLUSIONS: Implementation of the bundle measures
      included in the "Pneumonia Zero" project resulted in a significant reduction of
      more than 50% of the incidence of ventilator-associated pneumonia in Spanish
      ICUs. This reduction was sustained 21 months after implementation.

PMID- 29023263
TI  - MULTIMODAL IMAGING ADDS NEW INSIGHTS INTO ACUTE SYPHILITIC POSTERIOR PLACOID
      CHORIORETINITIS.
AB  - PURPOSE: Acute syphilitic posterior placoid chorioretinitis (ASPPC) is an
      uncommon manifestation of ocular syphilis with distinct clinical features. We
      describe new multimodal imaging findings in a patient with ASPPC. METHODS:
      Observational case report with multimodal imaging. RESULTS: A 44-year-old woman
      presented with 5 days of decreased vision in her right eye. Visual acuity was
      counting fingers in her right eye and 20/20 in her left eye. Funduscopic
      examination of the right eye showed a yellow placoid macular lesion with
      extension beyond the equator, which was encircled by an annular ring of outer
      retinal whitening. Ultra-widefield fundus autofluorescence demonstrated
      hyperautofluorescence corresponding to the placoid lesion. Examination of the
      left eye appeared unremarkable, but ultra-widefield fundus autofluorescence
      showed an area of hyperautofluorescence located superonasal to the optic nerve.
      Optical coherence tomography of the right eye demonstrated subretinal fluid and
      overlying disruption of the ellipsoid zone. Fluorescein angiography demonstrated
      early hypofluorescent and hyperfluorescent spots and late staining within the
      placoid lesion. Optical coherence tomography angiography showed several areas of
      decreased flow signal within the placoid lesion at the level of the
      choriocapillaris. Laboratory testing revealed a rapid plasma reagin titer of
      1:1,024. Two months after treatment with intravenous penicillin G, visual acuity
      had improved to 20/25 in her right eye, and optical coherence tomography showed
      partial restoration of the ellipsoid zone. The annular ring resolved with near
      normalization of fundus autofluorescence and optical coherence tomography
      angiography demonstrated resolution of flow. CONCLUSION: Multimodal imaging
      provides further insight into the pathogenesis of ASPPC. Ultra-widefield fundus
      autofluorescence may show evidence of ellipsoid zone disruption in areas that
      clinically appear normal. Flow voids within the choriocapillaris in ASPPC appear
      to resolve with appropriate treatment, a finding that suggests a transient
      disruption of choriocapillaris flow in ASPPC.

PMID- 29023264
TI  - Survival trends among patients with metastatic melanoma in the pretargeted and
      the post-targeted era: a US population-based study.
AB  - In 2011, ipilimumab was approved by the US Food and Drug Administration (FDA) for
      metastatic melanoma. Since its approval, numerous targeted therapies have been
      approved by the FDA. Population-based studies assessing the survival benefit from
      these agents are lacking. We therefore carried out this study to compare the 1
      year, 2-year, and median overall survival (OS) among metastatic melanoma patients
      in pretargeted and post-targeted eras. This is a retrospective study that
      utilized the Surveillance, Epidemiology, and End Results (SEER-18) database,
      version 8.3.4 (22 March 2017). The patient groups were defined as the pretargeted
      era (2004-2010) and the post-targeted era (2011-2014) as ipilimumab was approved
      by the FDA in 2011. The database comprised of 5471 patients (3314 in the
      pretargeted era and 2157 in the post-targeted era). OS in the post-targeted era
      was found to be significantly better compared with the pretargeted era by Kaplan
      Meier curve (1-year OS: 38.9 vs. 36.8%, 2-year OS: 28.3 vs. 23.5%, and median
      survival: 8 vs. 7 months, P=0.001 by the log-rank test). The survival was
      significantly better in the post-targeted era compared with the pretargeted era
      on multivariate analysis using a Cox proportional hazard model after adjusting
      for age, sex, race, and metasectomy status (adjusted hazard ratio of 0.889, 95%
      CI: of 0.832-0.951, P=0.001). There is significant survival benefit in metastatic
      melanoma patients since the introduction of immune checkpoint-blocking agents.

PMID- 29023265
TI  - Radial head resection and hemi-interposition arthroplasty in patients with
      multiple hereditary exostoses: description of a new surgical technique.
AB  - Multiple hereditary exostoses (MHE) are a rare disorder characterized by the
      growth of bony protrusions. Elbow involvement is found in a considerable number
      of patients and varies from the presence of a simple osteochondroma to severe
      forearm deformities and radial head dislocation. Patients encounter a variety of
      symptoms, for example, pain, functional impairment, and cosmetic concerns.
      Several types of surgical procedures, therefore, can be offered, ranging from
      excision of symptomatic osteochondromas to challenging reconstructions. In this
      paper, we will discuss the essential basics of visualizing, planning, and
      treatment options of forearm deformities in MHE. In more detail, we will describe
      our current surgical technique as a salvage procedure for Masada type II forearm
      deformities in patients with MHE.

PMID- 29023266
TI  - Novel ZBTB24 Mutation Associated with Immunodeficiency, Centromere Instability,
      and Facial Anomalies Type-2 Syndrome Identified in a Patient with Very Early
      Onset Inflammatory Bowel Disease.
AB  - BACKGROUND: Very early onset inflammatory bowel disease, diagnosed in children
      <=5 years old, can be the initial presentation of some primary
      immunodeficiencies. METHODS: In this study, we describe a 17-month-old boy with
      recurrent infections, growth failure, facial anomalies, and inflammatory bowel
      disease. Immune evaluation, whole-exome sequencing, karyotyping, and methylation
      array were performed to evaluate the child's constellation of symptoms and
      examination findings. RESULTS: Whole-exome sequencing revealed that the child was
      homozygous for a novel variant in ZBTB24, the gene associated with
      immunodeficiency, centromere instability, and facial anomalies type-2 syndrome.
      CONCLUSION: This describes the first case of inflammatory bowel disease
      associated with immunodeficiency, centromere instability, and facial anomalies
      type-2 syndrome in a child with a novel disease-causing mutation in ZBTB24 found
      on whole-exome sequencing.

PMID- 29023267
TI  - Enhanced TH17 Responses in Patients with IL10 Receptor Deficiency and Infantile
      onset IBD.
AB  - BACKGROUND: IL10 receptor (IL10R) deficiency causes severe infantile-onset
      inflammatory bowel disease. Intact IL10R-dependent signals have been shown to be
      important for innate and adaptive immune cell functions in mice. We have
      previously reported a key role of IL10 in the generation and function of human
      anti-inflammatory macrophages. Independent of innate immune cell defects, the aim
      of the current study was to determine the role of IL10R signaling in regulating
      human CD4 T-cell function. METHODS: Peripheral blood mononuclear cells and
      intestinal biopsies cells were collected from IL10/IL10R-deficient patients and
      controls. Frequencies of CD4 T-cell subsets, naive T-cell proliferation,
      regulatory T cell (Treg)-mediated suppression, and Treg and TH17 generation were
      determined by flow cytometry. Transcriptional profiling was performed by
      NanoString and quantitative real-time polymerase chain reaction. RNA in situ
      hybridization was used to determine the quantities of various transcripts in
      intestinal mucosa. RESULTS: Analysis of 16 IL10- and IL10R-deficient patients
      demonstrated similar frequencies of peripheral blood and intestinal Tregs,
      compared with control subjects. In addition, in vitro Treg suppression of CD4 T
      cell proliferation and generation of Treg were not dependent on IL10R signaling.
      However, IL10R-deficient T naive cells exhibited higher proliferative capacity, a
      strong TH17 signature, and an increase in polarization toward TH17 cells,
      compared with controls. Moreover, the frequency of TH17 cells was increased in
      the colon and ileum of IL10R-deficient patients. Finally, we show that
      stimulation of IL10R-deficient Tregs in the presence of IL1beta leads to enhanced
      production of IL17A. CONCLUSIONS: IL10R signaling regulates TH17 polarization and
      T-cell proliferation in humans but is not required for the generation and in
      vitro suppression of Tregs. Therapies targeting the TH17 axis might be beneficial
      for IL10- and IL10R-deficient patients as a bridge to allogeneic hematopoietic
      stem cell transplantation.

PMID- 29023268
TI  - Surgical Simulation Training Reduces Intraoperative Cataract Surgery
      Complications Among Residents.
AB  - INTRODUCTION: This retrospective consecutive case series examined whether
      training on a surgical simulator reduces intraoperative complication rates among
      novice ophthalmology residents learning cataract surgery. METHODS: Beginning July
      2014, training on the Eyesi simulator became mandatory for novice postgraduate
      year 3 ophthalmology residents before live cataract surgery at our institution.
      Complication rates of the 11 simulator-trained residents (study group) were
      compared with their immediate 11 simulator-naive predecessors (comparison group).
      Only straightforward cataract cases (according to standardized preoperative
      criteria) where postgraduate year 3 residents served as the primary surgeon were
      included. Complication data were obtained from Morbidity and Mortality records
      and compared using Fisher exact test. A survey was administered to the residents
      to gauge the perceived utility of simulation training. RESULTS: The simulator
      trained group (n = 501 cataract cases) and the simulator-naive comparison group
      (n = 454 cases) were analyzed. The complication rate in the simulator group was
      2.4% compared with 5.1% in the comparison group (P = 0.037, Fisher exact test).
      Both the mean posterior capsule tear rate and vitreous prolapse rate in the
      simulator group were 2.2% compared with 4.8% in the comparison group (P = 0.032,
      Fisher exact test). The survey had a response rate of 100% (11/11), and 91%
      (10/11) of respondents felt that the training was "extremely worthwhile" and
      should be mandatory. CONCLUSIONS: The addition of surgical simulation training
      was associated with a significantly reduced rate of complications, including
      posterior capsule tears and vitreous prolapse, among novice postgraduate year 3
      residents. There is a perceived utility among residents to incorporate virtual
      simulation into surgical training.

PMID- 29023270
TI  - Nursing Education and the 21st Century Library.

PMID- 29023269
TI  - ALL-PROBE VITRECTOMY DISSECTION TECHNIQUES FOR DIABETIC TRACTIONAL RETINAL
      DETACHMENTS: Lift and Shave.
AB  - PURPOSE: To describe the all-probe lift and shave technique to remove
      fibrovascular tissue and repair diabetic retinal detachments. Anatomical and
      visual acuity outcomes with this technique are presented. METHODS: In this single
      surgeon, retrospective review of a consecutive series of eyes with tractional
      retinal detachment associated with diabetic retinopathy repaired with probe-only
      dissection techniques. The technique of alternating aspiration with blunt
      dissection and shaving with the vitrectomy probe is described and shown in video.
      RESULTS: Forty-two eyes with tractional retinal detachment were successfully
      repaired and achieved anatomical attachment with the lift and shave technique.
      Twenty eyes were repaired with 27 g vitrectomy and 22 eyes with 25 g. Ninety
      percent of eyes improved two or more Snellen lines. Minimum follow-up was 6
      months. Complications included iatrogenic breaks in one eye (5%), nonclearing
      vitreous hemorrhage in four eyes (9%), and reoperation in three eyes (7%) for
      epiretinal membranes. CONCLUSION: The all-probe lift and shave technique of
      fibrovascular dissection is a streamlined approach for the management of
      tractional retinal detachments. Advantages include the need for minimal ancillary
      instrumentation, increased efficiency, and reduced complications.

PMID- 29023271
TI  - Dual-Task Tandem Gait and Average Walking Speed in Healthy Collegiate Athletes.
AB  - OBJECTIVES: To (1) examine the association between a commonly used concussion
      test, tandem gait, in single/dual-task conditions with single-task and dual-task
      average walking speed, (2) characterize the prevalence of tandem gait false
      positives, and (3) develop a normative reference range of dual-task tandem gait
      times. DESIGN: Cross-sectional study. SETTING: Two NCAA collegiate athletic
      facilities. INDEPENDENT VARIABLES: Athletes completed the tandem gait test and a
      gait evaluation in single/dual-task conditions during a preseason examination.
      MAIN OUTCOME MEASURES: Associations between tandem gait times and average walking
      speeds were evaluated using multiple linear regression models. Various tandem
      gait test time pass/fail cutoffs were calculated to examine false-positive rates.
      RESULTS: Among the 171 participants (103 men, 19.8 +/- 1.2 years of age), dual
      task tandem gait completion times were independently associated with dual-task
      average walking speed [beta = -4.018; 95% confidence interval (CI), -7.153 to 
      0.883], but single-task associations were not found. Male gender was associated
      with faster tandem gait times in both single-task (beta = -0.880, 95% CI, -1.731
      to -0.029) and dual-task conditions (beta = -2.225, 95% CI, -3.691 to -0.759). A
      pass/fail cutoff threshold of 14 seconds resulted in a 2% false-positive rate for
      single-task tandem gait, while it resulted in a 29% false-positive rate during
      dual-task tandem gait. CONCLUSIONS: Average walking speed and dual-task tandem
      gait represent objective measures that are useful in concussion management. While
      a single-task tandem gait cutoff of 14 seconds seems appropriate for males,
      adjustments may be necessary based on sex and alternate pass/fail criteria may be
      appropriate for dual-task tandem gait.

PMID- 29023272
TI  - Sensitivity of the Cogstate Test Battery for Detecting Prolonged Cognitive
      Alterations Stemming From Sport-Related Concussions.
AB  - OBJECTIVE: To determine if the Cogstate test battery contains the requisite
      sensitivity to detect prolonged cognitive alterations. METHODS: One hundred
      twenty collegiate athletes (71 with a history of concussion; 49 controls)
      completed the Cogstate test battery, to which we added a 2-back condition. In
      addition to the Cogstate clinical (transformed variables), we analyzed the raw
      data. RESULTS: The clinical variables failed to reveal any group differences.
      Further, although the raw data failed to reveal group differences for tasks
      measuring lower-level cognition, group differences were observed for accuracy on
      the 1- and 2-back tasks, which require multiple aspects of higher cognition. The
      overall classification accuracy was higher using the raw data than the clinical
      variables. The combined sensitivity of the 1- and 2-back task was moderate and
      specificity was high. CONCLUSIONS: These results suggest that using the raw
      scores over clinical variables increases the sensitivity of the test battery.
      Moreover, these results add another piece of evidence suggesting that concussive
      injuries are associated with subtle long-term alterations in aspects of higher
      cognition. Importantly, these deficits would have gone unobserved if we had
      relied solely on automated clinical variables. The current results further our
      scientific understanding of concussion and may be used to advance clinical
      practices.

PMID- 29023273
TI  - Return to Sports After Athletes Undergo Meniscal Surgery: A Systematic Review.
AB  - OBJECTIVE: The aim of this systematic review was to determine the time to and
      rate of the return to sports (RTS) after meniscal surgery and to compare these
      values among the different types of meniscal surgeries. STUDY DESIGN: Systematic
      review. METHODS: The MEDLINE, EMBASE, and Cochrane databases were searched.
      Studies that met the following criteria were included: (1) English article, (2)
      full-text available, (3) study on athletes, and (4) primary outcome is RTS after
      meniscal surgery, such as meniscectomy, meniscal repair, and meniscal allograft
      transplantation (MAT). RESULTS: Eleven articles were included in the final
      analysis. Most players returned to the preinjury activity level from 7 to 9 weeks
      after partial meniscectomy. After meniscal repair, 81% to 88.9% of athletes
      returned to sports. The time to RTS after isolated meniscal repair was on average
      5.6 months, and the time to RTS was longer for athletes who required concurrent
      anterior cruciate ligament reconstruction (ACLR). After MAT, 67% to 85.7% of
      athletes returned to sports, and the time to RTS ranged from 7.6 to 16.5 months.
      CONCLUSIONS: The shortest time to RTS and the highest RTS rate were observed
      after partial meniscectomy. The time to RTS was shorter, and the RTS rate was
      higher after meniscal repair than after MAT. Concurrent procedures such as ACLR
      prolonged the time to RTS, but it had no effect on the RTS rate and the level of
      sports activity at the time of RTS.

PMID- 29023274
TI  - The Injury and Illness Profile of Male and Female Participants in a 94.7 km Cycle
      Race: A Cross-Sectional Study.
AB  - OBJECTIVE: To describe the incidence and patterns of injury and illness of male
      and female participants during a 94.7 km distance cycling event. DESIGN:
      Descriptive study. SETTING: Momentum 94.7 Cycle Challenge 2014. PARTICIPANTS: All
      23 055 race starters (males = 17 520, females = 5236, not specified = 299). MAIN
      OUTCOME MEASURES: The incidence and type of all medical complaints and difference
      between sexes. RESULTS: Incidence (per 1000 race starters) of all medical
      complaints was 38.69 (males = 36.52, females = 38.39), adverse medical events
      11.88 (males = 10.73, females = 16.42) and serious adverse events 1.3 (males =
      0.86, females = 2.67). The incidence of nontraumatic medical complaints was 32.49
      (males = 33.39, females = 31.32) and of traumatic injuries was 3.99 (males =
      3.14, females = 7.07). Females compared to males had a higher risk of sustaining
      traumatic injuries (P < 0.001), central nervous system, (P = 0.0062) and eye
      complaints (P = 0.0107). Most complaints (80.6%) were reported for the
      musculoskeletal system. Males 10-15 years (P = 0.0013) and females 23-39 years (P
      = 0.0336), and older than 50 years (P = 0.0002) had a higher than expected risk
      for traumatic injuries. CONCLUSIONS: Medical complaints ratio reported was 1:26
      (males = 1:28, females = 1:26) in all starters during the cycling event. Cyclists
      that did not finish the race (adverse events) were 1:84 (males = 1:93, females =
      1:61). Serious adverse events that required hospitalization were 1:769 (males =
      1:1163, females = 1:374). The majority of admissions were for traumatic injuries,
      followed by cardiovascular complaints. Results from this study indicated that a
      wide spectrum of medical complaints can be expected during such an event with a
      higher risk for females to sustain traumatic injuries and to encounter central
      nervous system and eye complaints. Information regarding the pattern and type of
      medical encounters can prove useful during planning and management of similar
      future events.

PMID- 29023275
TI  - Proximal Radial Head Fractures in Young Gymnasts: A Case Series of Newly
      Described Overuse Injuries.
AB  - We report a case series of unilateral Salter-Harris IV fractures of the proximal
      radial heads in young female gymnasts. To date, there are no previous reports of
      such injuries in gymnastics. In all 3 athletes, no significant injury preceded
      presentation or diagnosis. Radiographs and magnetic resonance imaging showed
      fractures and associated bone marrow edema of the proximal radial head,
      respectively. All but 1 was treated nonoperatively with success. Given the lack
      of acute trauma, lack of large effusion, and good range of motion at
      presentation, these injuries are believed to be chronic in nature and related to
      overuse. This case series highlights the need for routine surveillance and the
      limiting of upper extremity weight bearing when possible in gymnasts.

PMID- 29023276
TI  - Epidemiology of Competition Injuries in Elite European Judo Athletes: A
      Prospective Cohort Study.
AB  - OBJECTIVE: To determine the injury incidence rate (IIR) and injury pattern, and
      to identify risk factors for injury, among elite adult European judo athletes.
      DESIGN: Prospective cohort study. SETTING: The 2015 Under 23 European Judo
      Championships, Bratislava, Slovakia. PARTICIPANTS: All registered athletes (N =
      295). INDEPENDENT VARIABLES: Sex, weight division, and fight outcome. MAIN
      OUTCOME MEASURES: Injury incidence rates were calculated per 1000 athlete
      exposures (IIRAE) and per 1000 minutes of exposure (IIRME) with 95% confidence
      intervals (CI). Subgroups were compared by calculating the injury incidence rate
      ratio (RR) with a 95% CI. RESULTS: The overall IIRAE and IIRME were 35.6 (95% CI,
      22.8-53.0) and 10.9 (95% CI, 7.0-16.2), respectively. The most frequently injured
      anatomical region was the head/neck (41%), whereas the most common type of injury
      was contusion (33%). The risk of injury was almost 4 times greater for defeated
      athletes compared with winners [RRME 3.80 (95% CI, 1.47-9.82)]. Athletes in
      middleweight divisions had a greater risk of injury compared with their
      lightweight [RRME 3.58 (95% CI, 1.24-10.35)] and heavyweight [RRME 2.34 (95% CI,
      0.93-5.89)] counterparts. The risk of injury for women was not significantly
      different from their male counterparts [RRME 1.33 (95% CI, 0.61-2.90)].
      CONCLUSIONS: Weight division (middle) and fight outcome (losing) are significant
      risk factors for injury. The IIR in elite adult judo competition is lower than
      that in taekwondo and karate. Future research is encouraged to investigate the
      actual severity of judo injuries, and to investigate potentially modifiable risk
      factors to mitigate the risk of injury in judo.

PMID- 29023277
TI  - Diagnosis and Treatment of Slipping Rib Syndrome.
AB  - OBJECTIVE: (1) To investigate the clinical presentation, diagnosis, and treatment
      of slipping rib syndrome in athletes; (2) to investigate the hooking maneuver for
      diagnosis of slipping rib syndrome. DESIGN: Retrospective chart review of 362
      athletes with rib pain. SETTING: Pediatric-based sports medicine clinic between
      January 1, 1999, and March 1, 2014. PATIENTS: Costochondritis, Tietze, fractures,
      rib tip syndrome, and unclear diagnoses were excluded. Athletes were included who
      had a palpable rib subluxation, mechanical rib symptom, positive hooking
      maneuver, or resolution of pain after the resection of a slipping rib segment.
      MAIN OUTCOME MEASURES: Slipping rib syndrome is associated with athletic
      performance. RESULTS: Fifty-four athletes were diagnosed with slipping rib
      syndrome, of which 38 (70%) were females. Mean age at presentation was 19.1 years
      (range 4-40 years). Mean number of previous specialist consultations per athlete
      was 2.3 and mean time from symptom onset to diagnosis was 15.4 months. The
      hooking maneuver was attempted 21 times (38.9%). Unilateral symptoms presented in
      49 athletes (90.7%). The most symptomatic rib was the 10th, affecting 24 athletes
      (44.4%), eighth and ninth were affected in 17 athletes (31.5%) each. Most, 39
      (72.2%), reported insidious onset of symptoms. Running, rowing, lacrosse, and
      field hockey were frequently associated activities. Twelve athletes had
      psychiatric diagnoses (22.2%), 10 (19.2%) were hypermobile. Sixty-six total
      imaging studies were performed. The most successful treatment options included:
      osteopathic manipulative treatment (71.4%), surgical resection (70%), and
      diclofenac gel (60%). CONCLUSIONS: Most athletes with slipping rib syndrome were
      active females with insidious onset of unilateral pain, a high prevalence of
      hypermobility and prolonged pain. The hooking maneuver was underused.

PMID- 29023278
TI  - Surgical Approach Impacts Posterior Femoral Cutaneous Nerve Outcomes After
      Proximal Hamstring Repair.
AB  - OBJECTIVE: The goal of this study was to characterize the risk of intraoperative
      injury to the posterior femoral cutaneous nerve and to evaluate potential risk
      factors for injury during surgical repair of proximal hamstring injuries. DESIGN:
      Retrospective cohort study. SETTING: Single tertiary referral center. PATIENTS:
      The cohort consisted of all patients presenting to a single institution with a
      proximal hamstring avulsion injury who were managed with surgical repair between
      January 1, 2000 and August 1, 2016. A total of 67 patients were included in the
      cohort. INDEPENDENT VARIABLES: Variables assessed for their association with
      postoperative numbness in the distribution of the posterior femoral cutaneous
      nerve included age, sex, body mass index, mechanism of injury, time to surgical
      repair, and incision used. MAIN OUTCOME MEASURES: The primary outcome of interest
      was neurologic symptoms referable to the posterior femoral cutaneous nerve.
      RESULTS: Postoperatively, 13 patients (19%) developed new numbness in the
      distribution of the posterior femoral cutaneous nerve. One patient reported
      neuropathic pain and paresthesias associated with the numbness. The use of a
      gluteal crease incision was the only predictive factor for postoperative numbness
      in the posterior femoral cutaneous nerve distribution (odds ratio 8.67; 95%
      confidence interval, 2.30-42.80; P = 0.001). CONCLUSIONS: The current study
      provides data that can be used in discussing the risks and benefits of surgical
      repair with patients and when weighing the pros and cons of using a gluteal
      crease versus longitudinal incision.

PMID- 29023279
TI  - Syncope Episodes and Blood Flow Restriction Training.
AB  - The combination of low-load resistance training [or more recently, neuromuscular
      electrical stimulation (NMES)] with a moderate local blood flow restriction (BFR)
      is becoming a widespread training and rehabilitation method. Scientific data
      indicate the overall safety of BFR, at least in healthy young people. However, it
      has been associated with side effects, usually minor, and further research is
      warranted regarding the safety and efficacy of this technique, especially in
      clinical populations. We found 3 syncope/presyncopal episodes among 21 healthy
      people (9 men), all occurring in men and during familiarization sessions (in
      which BFR was applied alone) but not thereafter (BFR sessions combined with
      NMES): 1 subject experienced a brief syncope and 2 other subjects exhibited
      presyncopal symptoms (sweating, lightheadedness, and pallor). Our cases are
      evidence that cardiovascular complications may emerge during BFR. Caution is thus
      needed in the application of BFR, and gentle familiarization with this training
      modality is also recommended.

PMID- 29023280
TI  - Corrective Exercises Improve Movement Efficiency and Sensorimotor Function but
      Not Fatigue Sensitivity in Chronic Ankle Instability Patients: A Randomized
      Controlled Trial.
AB  - OBJECTIVE: To investigate the effect of corrective exercises on functional
      movement patterns, sensorimotor function, self-reported function, and fatigue
      sensitivity in collegiate athletes with chronic ankle instability (CAI). DESIGN:
      A randomized controlled trial. SETTING: Laboratory of sports sciences.
      PARTICIPANTS: Forty male volunteers were randomly assigned to the experimental
      group (age 21.2 +/- 1.7 years, height 174.5 +/- 6.1 cm, and weight 69.6 +/- 6.9
      kg) or the control group (age 20.9 +/- 1.8 years, height 178.2 +/- 6.6 cm, and
      weight 68.8 +/- 8.1 kg). INTERVENTION: Participants in the experimental group
      performed supervised corrective exercises 3 times per week for 8 weeks. Fatigue
      was induced with a progressive treadmill protocol before and after the 8-week
      intervention. MAIN OUTCOME MEASURES: Outcomes included movement efficiency during
      3 squat tasks, static and dynamic postural control, strength of the ankle
      musculature, joint position sense, and self-reported function with the Foot and
      Ankle Ability Measure subscales. These outcomes were assessed before and
      immediately after fatiguing treadmill running both before and after 8-weeks of
      corrective exercises. RESULTS: Significant improvements in movement efficiency,
      sensorimotor function, and self-reported function were noted in the experimental
      group relative to the control group (P < 0.001), in a nonfatigued state. However,
      in a fatigued stated, the experimental intervention only improved static postural
      control (P = 0.016) relative to the control group. CONCLUSIONS: These findings
      demonstrate that 8-weeks of corrective exercises were effective at enhancing
      movement efficiency, sensorimotor function, and self-reported function in
      collegiate athletes with CAI. However, this intervention program has limited
      abilities at reducing the effects of fatigue.

PMID- 29023281
TI  - Proton Pump Inhibitor and H2 Blocker-Associated Acute Interstitial Nephritis in a
      Renal Allograft.

PMID- 29023282
TI  - Abatacept Monotherapy Versus Abatacept Plus Methotrexate for Treatment-Refractory
      Rheumatoid Arthritis.
AB  - BACKGROUND: Methotrexate combination therapy improves abatacept efficacy as a
      first-line biologic agent for the treatment of rheumatoid arthritis, but it is
      unclear when abatacept is used later on, particularly after non-TNF inhibitor
      (TNFi) failure. STUDY QUESTION: The objective of this study was to determine
      whether treatment response after non-TNFi inadequate response is different in
      patients with rheumatoid arthritis (RA) treated with abatacept in combination
      with or not with methotrexate. METHODS: Patients treated with abatacept
      monotherapy or in combination with methotrexate after non-TNFi failure were
      included. RESULTS: Data from 46 patients aged 56 years [49-61] with 12 years [8
      16] of disease duration were examined. Rituximab was the treatment used in the
      previous line for 75.0% of the combination therapy group (15/20) and 34.6% (9/26)
      in the monotherapy group. At 12 months, 38.5% (10/26) of patients were in good-to
      moderate EULAR response in the monotherapy group compared with 25.0% (5/20) in
      the combination therapy group (P = 0.33). Treatment persistence at 12 months was
      61.5% (16/26) in the monotherapy group and 35.0% (7/20) in the combination
      therapy group (P = 0.07). CONCLUSIONS: Adding methotrexate to abatacept did not
      improve treatment response in patients with RA after non-TNFi inadequate
      response.

PMID- 29023283
TI  - Big data gets even bigger.

PMID- 29023284
TI  - Harnessing the power of artificial intelligence.

PMID- 29023285
TI  - Predictors of Electroconvulsive Therapy Use in a Large Inpatient Psychiatry
      Population.
AB  - OBJECTIVE: There is limited research on reliable and clinically useful predictors
      of electroconvulsive therapy (ECT) use. We aimed to examine factors that predict
      ECT use in an inpatient psychiatric population. DESIGN: Retrospective analysis of
      provincial database for inpatient psychiatry. METHODS: This study is a
      retrospective analysis of a provincial database for inpatient psychiatry. The
      study includes all psychiatric inpatients 18 years or older in Ontario, Canada,
      assessed with the Resident Assessment Instrument for Mental Health (RAI-MH)
      within the first 3 days of admission between 2009 and 2014 (n = 153,023). The RAI
      MH is a validated assessment tool which includes a breadth of information on
      symptoms, self-harm, functioning, social support, comorbid medical diagnoses, and
      risk appraisal. Multivariable analyses were performed using SAS. RESULTS: One
      hundred forty-five thousand seven hundred (95.2%) of patients admitted had no
      history of ECT treatment and were not scheduled to receive ECT. A total of 7323
      (or 4.8% of the patient population) had either a history of ECT use or were
      scheduled to receive ECT. Overall rate of ECT use was highest in patients with a
      provisional diagnosis of mood disorder (7.2%) compared with schizophrenia/other
      psychotic disorder (3.1%) or substance-related disorder (1.7%). Women were more
      likely to receive ECT compared with men (overall rates of ECT use 6.2% and 3.4%,
      respectively). Overall rate of ECT use increased significantly with increasing
      age. Number of prior hospitalizations was also a strong predictor of ECT use.
      Conversely, patients with elevated Risk of Harm to Others, schizophrenia, or a
      substance use disorder were all significantly less likely to receive ECT. All
      variables examined were statistically significant (P < 0.0001). Higher Severity
      of Self Harm Scores predicted past use, but not scheduled use of ECT.
      CONCLUSIONS: This is the largest study to date on predictors of ECT use.
      Utilization of RAI-MH is a novel and clinically useful method for evaluating
      predictors of ECT use. Predictors of ECT use within an inpatient population
      include: presence of a mood disorder, female sex, older age, low risk of harm to
      others, number of lifetime hospitalizations, lack of substance use disorder, and
      inability to care for self.

PMID- 29023286
TI  - STI Versus STD: Coda.

PMID- 29023287
TI  - Effects of illusory kinesthesia by tendon vibratory stimulation on the
      postoperative neural activities of distal radius fracture patients.
AB  - Activation of motor-related regions with illusory kinesthesia had been suspected
      to contribute toward pain alleviation. We used electroencephalography (EEG) to
      assess the sensorimotor cortex activation during illusory kinesthesia by
      vibratory tendon stimulation in patients who were in pain. We investigated the
      relationship between the sensorimotor cortex and postoperative pain to clarify
      the analgesia mechanism. Patients who had undergone distal radius fracture
      surgery were studied. A hand massager provided the vibration stimulus for the
      illusory kinesthesia on the extensor digitorum muscle at the nonaffected hand's
      wrist joint on 7 consecutive days starting 1 day after surgery. The main outcomes
      were pain intensity and EEG activity. EEG activity was recorded during illusory
      kinesthesia. We also analyzed the high alpha rhythm (10-12 Hz) event-related
      desynchronization/event-related synchronization. The pain intensity was reduced.
      Attenuation of the high alpha wave was observed in the bilateral sensorimotor
      cortex (C3ch, C4ch) areas during illusory kinesthesia. A significant negative
      correlation was also observed in the C3 and the C4 of event-related
      desynchronization/event-related synchronization% values and the variation of pain
      amelioration at rest. Activation of the sensorimotor cortex by illusory
      kinesthesia might have influenced parts of the descending pain-inhibitory system.
      The postoperative pain in the patients might have been alleviated by the
      descending pain-inhibitory system.

PMID- 29023289
TI  - Parental Perceptions Following Cleft Lip Repair in Their Children.
AB  - OBJECTIVE: Cleft lip (CL) repair at 3 months is chosen mostly out of convention
      and offers minimal functional benefit. Potentially, a better cosmetic outcome is
      possible by delaying repair. This study examines parental perceptions around
      repair at 3 months to determine if current guidelines are appropriate. DESIGN:
      Retrospective cross-sectional survey. SETTING: Tertiary-care institution.
      PARTICIPANTS: Parents of children with CL +/- P under age 6 years who underwent
      CL repair from 2004 to 2011 at our center were surveyed (n = 64). Response rate
      was 61% (n = 37). METHODS: Open-ended survey asked about various aspects of
      parental perceptions before and after repair. Qualitative data analysis is used
      to interpret survey responses. STATISTICS: Fisher exact test using contingency
      tables to identify statistically significant results. RESULTS: Nearly all (36/37)
      parents felt repair was important, citing reasons such as feeding, speech, and
      appearance. Most (28/37) felt surgery would fix the problem. A portion of parents
      (15/37) would delay repair if better aesthetics were possible later, but most
      would not (20/37). Most parents were satisfied with repair quality (33/37). On
      average, repair did not impact parent-child bonding, and eliminated negative
      interactions with strangers that parents found distressing. CONCLUSIONS:
      Arguably, positive parental perceptions of their child's condition reflect
      favorably on the child's well-being, and may outweigh any future aesthetic
      benefit. Therefore, current recommendations should be upheld. However, given that
      some parents would consider delaying repair, they could be offered this option.
      Future efforts should examine cultural factors, and aesthetic and developmental
      outcomes of repair at different ages to determine optimal repair timing.

PMID- 29023288
TI  - Gut microbiome and its role in cardiovascular diseases.
AB  - PURPOSE OF REVIEW: In recent years, an interest in intestinal microbiota-host
      interactions has increased due to many findings about the impact of gut bacteria
      on human health and disease. Dysbiosis, a change in the composition of the gut
      microbiota, has been associated with much pathology, including cardiovascular
      diseases (CVD). This article will review normal functions of the gut microbiome,
      its link to CVD, and potential therapeutic interventions. RECENT FINDINGS: The
      recently discovered contribution of gut microbiota-derived molecules in the
      development of heart disease and its risk factors has significantly increased
      attention towards the connection between our gut and heart. The gut microbiome is
      virtually an endocrine organ, arguably the largest, capable of contributing to
      and reacting to circulating signaling molecules within the host. Gut microbiota
      host interactions occur through many pathways, including trimethylamine-N-oxide
      and short-chain fatty acids. These molecules and others have been linked to much
      pathology including chronic kidney disease, atherosclerosis, and hypertension.
      SUMMARY: Although our understanding of gut microbiota-host interactions has
      increased recently; many questions remain about the mechanistic links between the
      gut microbiome and CVD. With further research, we may one day be able to add gut
      microbiota profiles as an assessable risk factor for CVD and target therapies
      towards the gut microbiota.

PMID- 29023291
TI  - Craniocervical Pseudomeningocele Following Cerebellar Meningioma Resection:
      Demonstration of Neck of Pseudomeningocele With Three-Dimensional Isotropic T2
      Weighted SPACE Sequence at 3 Tesla (3T) Magnetic Resonance Imaging.
AB  - Postoperative pseudomeningocele is an uncommon complication of craniospinal
      surgery. Diagnosis is reached on a postoperative computed tomography and magnetic
      resonance (MR) imaging. Demonstration of the location and dimension of the dural
      defect before surgical therapy is a very important. T1- and T2-weighted MR images
      revealed a significant pseudomeningocele extending from left cervicooccipital
      region. Magnitude and phase-contrast-MR images showed a cerebrospinal fluid (CSF)
      flow into pseudomeningocele, but they no revealed dural defect. Three-dimensional
      isotropic T2-weighted SPACE sequence revealed a signal void indicating CSF flow
      into pseudomeningocele and location and exact size of dural tear. Three
      dimensional isotropic T2-weighted SPACE sequence is certainly the noninvasive and
      optimal method for demonstrating postoperative pseudomeningocele sacs. It
      demonstrates a pseudomeningocele regardless of an existing communication with the
      dural membrane.

PMID- 29023290
TI  - Fascial Graft Repair of Wide Bilateral Cleft Lip Deformity.
AB  - Wide bilateral cleft lip deformity reconstruction represents a special difficulty
      as it affects the lip, nose, and maxillary segments making single-stage
      reconstruction sometimes unobtainable. Many surgical and nonsurgical techniques
      have been prescribed to facilitate the definitive repair. Although some of these
      techniques proved to be useful, they have their inherent limitations and add
      another treatment step with all its possible complications and costs. The authors
      present a new method to address muscle layer repair in 1-stage procedure. It
      entails using fascial graft obtained from the temporalis muscle fascia or fascia
      lata, to reconstruct orbicularis oris lip muscle. Seven patients of wide
      bilateral cleft lip deformity (mean 17 mm) with a mean age of 4.4 months were
      subjected to single-stage lip reconstruction. After measuring the defect between
      both lateral muscle segments in front of the premaxilla intraoperatively ensuring
      that direct muscle repair could not be obtained, a fascial graft was harvested
      and sutured to both muscle edges. The authors found that, regardless the defect
      size or premaxilla protrusion, all wide clefts could be reconstructed
      satisfactorily in 1 stage procedure. No serious postoperative complications have
      been encountered in the lip or donor areas. Early follow-up reporting of the
      patients revealed stable repair. However more follow-up is still needed to assess
      late sequelae. In conclusion, fascial graft muscle repair of wide bilateral cleft
      lip deformity enables early 1-stage lip reconstruction without tension. The added
      donor morbidity is minimal and well tolerated.

PMID- 29023292
TI  - Silicone Facial Prosthesis: A Preliminary Report on Silicone Adhesion to Magnet.
AB  - Although a silicone facial prosthesis has many advantages, silicone's limited
      cementation with resin or metal has caused many maxillofacial reconstructive
      surgeons and prosthodontists concern regarding the use of silicone-based facial
      prostheses. This study demonstrates 1 representative silicone facial prosthesis
      patient with magnet cementation to silicone using plastic clay, which will be
      applied to various maxillofacial prosthesis strategies in the near future.

PMID- 29023293
TI  - Form, Function, and Esthetics in Prosthetically Rehabilitated Maxillary Defects.
AB  - PURPOSE: Patients with maxillofacial defects secondary to the removal of benign
      and malignant pathologies of midface have a profound impact on quality of life.
      The aim of this study was to collect and analyze the data pertaining to 4 designs
      of obturator by assessment of the patient with obturator functioning scale (OFS)
      MATERIALS AND METHODS:: This retrospective analysis included all the patients who
      underwent prosthetic rehabilitation of maxillary defects using 4 different types
      (conventional, cast partial, hollow bulb, and magnet retained) of obturators from
      2009 to 2016 with minimum 1 year of follow up. Demographics, number, size,
      location, type of pathology, postmorbid dentition, and the treatment rendered
      were recorded. Obturator functioning scale was used to subjectively assess the
      patient satisfaction. RESULTS: The mean score on OFS was 5.67 (standard
      deviation: 1.8). There was a fair and statistical improvement in chewing/eating,
      speech clarity in public/on phone, swallowing of foods and liquids, pronunciation
      of words, and social interaction (P < 0.05). The outcome was best in magnet
      retained followed by cast partial group. The least outcome was in conventional
      obturator group. CONCLUSION: Obturators of different designs do play an important
      role in rehabilitation of maxillary defects with a satisfactory outcome.

PMID- 29023295
TI  - Craniofacial Surgery in Chile.

PMID- 29023294
TI  - Cleft Lip and Palate: Demographic Patterns and the Associated Communication
      Disorders.
AB  - PURPOSE: This study investigated demographical characteristics, health status,
      and associated communication disorders in patients with orofacial clefts (OFCs)
      in Northern Jordan. METHODS: A retrospective study of 226 cleft patients and
      their families was carried out between March 2012 and September 2016 at the
      Speech and Hearing Clinic and the Maxillofacial Center at King Abdullah
      University Hospital. Data were collected by interviewing patients and caregivers,
      having patients or caregiver to complete a questionnaire and reviewing the
      patient's medical records. The frequencies of OFC type, demographic, health
      status, and communication disorders variables were calculated. chi analysis was
      used to test for significance of associated demographic and communication
      disorders variables with OFC type. RESULTS: Results revealed higher percentage of
      males compared with female patients. The majority of OFC patients were born to
      families who lived in urban areas, obtained high school diploma or lower
      educational level, lived below poverty cutoff, and showed nonconsanguineous
      marriages. Most mothers took the prescribed pregnancy supplements. Only one-third
      of the families received health education and reported other incidences of OFCs.
      Twenty percent of the patients had other congenital anomalies, 80% experienced
      dysphagia prior to the cleft repair, dropped to 14% after the repair. Higher
      percentage of patients with isolated cleft palate and cleft lip and palate
      exhibited hearing loss, hypernasality, articulation and phonological disorders,
      and dysphagia compared with those with cleft lip only. None of the demographic
      variables was associated with OFC type. CONCLUSIONS: Data suggested that families
      who had children with OFCs displayed poor socioeconomic status and low
      educational level which may impede the delivery of health education by health
      practitioners. Increased risk of comorbid communication disorders and
      malformations in OFC patients must be emphasized and disseminated to health
      professionals involved in the management of patients with OFC.

PMID- 29023296
TI  - Variability in Minimally Invasive Surgery for Sagittal Craniosynostosis.
AB  - Minimally invasive approaches to the surgical correction of sagittal
      craniosynostosis are gaining favor as an alternative to open cranial vault
      remodeling. In this systematic review, the reviewers evaluate the variability in
      described surgical techniques for minimally invasive correction of sagittal
      craniosynostosis. Articles were selected based on predetermined inclusion and
      exclusion criteria from an online literature search through PubMed, EMBASE, and
      the Cochrane library. Extracted data included the incisions, method of
      dissection, osteotomies performed, and type of force therapy utilized.A total of
      28 articles from 15 author groups were included in the final analysis. Of the 28
      articles, 17 distinct techniques were identified. Significant variation existed
      in both the technique and the terminology used to describe it. Access to the
      cranium varied between a standard bicoronal incision (n = 2), a "lazy S" incision
      (n = 2), and multiple short incisions along the fused sagittal suture (n = 13).
      Additional variations were found in the size and design of the osteotomy, the
      usage (and duration, if applicable) of force therapy, and the age of the patient
      at the time of surgical intervention.This systematic review demonstrates that
      minimally invasive approaches to sagittal craniosynostosis vary widely in
      technique with respect to the incisions, osteotomies, and force therapy used.
      Additionally, the terminology employed in describing minimally invasive
      approaches is inconsistent across centers. This discrepancy between technique and
      terminology presents challenges for reporting and interpreting the increasing
      body of literature on this subject. We recommend standard terminology be used for
      future publications on minimally invasive techniques.

PMID- 29023297
TI  - Evaluation of Sinonasal Change After Lefort I Osteotomy Using Cone Beam Computed
      Tomography Images.
AB  - Orthognathic surgery including Le Fort I osteotomy involves changes in the nasal
      septum and maxillary sinus. This study assesses nasal septum changes after Le
      Fort I osteotomy using cone beam computed tomography images and evaluates mucosal
      changes in the maxillary sinus after the surgery.This was a retrospective study
      of 33 patients who underwent orthognathic surgery including Le Fort I osteotomy.
      To assess the maxillary sinus, changes in the mucosa of the maxillary sinus were
      analyzed by volume and geometry. We measured the air cavity per se and mucosal
      thickening of the maxillary sinus using SIMPLANT (Materialise, Belgium) software.
      And the geometry of the distribution of the mucosa was analyzed using cone beam
      computed tomography images.The septal angle was decreased after surgery, but not
      significantly (P > 0.05). The volume reduction of the air cavity per se and the
      volume increase associated with mucosal thickening were statistically significant
      (P < 0.05). Mucosal thickening was observed in the posterior-inferior
      direction.In this study, nasal septum deviation was not statistically significant
      after Le Fort I osteotomy. Decrease of the air cavity per se, decrease of the
      total volume of the maxillary sinus, and increase of mucosal thickening were
      prominent. Furthermore, the mucosal thickening that occurs after surgery appears
      to be mainly in the posterior lower part of the maxillary sinus.

PMID- 29023298
TI  - Appraisal of Function After Rehabilitation With Tongue Prosthesis.
AB  - STATEMENT OF THE PROBLEM: Prosthetic rehabilitation following total glossectomy
      is very complex procedure from clinical as well as laboratory point of view. The
      basic objective of prosthodontic rehabilitation is to deliver a comfortable as
      well as esthetically suitable prosthesis, which restores the impaired speech and
      deglutition function. PURPOSE: Prosthetic rehabilitation of patients after total
      glossectomy with tongue prosthesis to evaluate improvement in speech as well as
      swallowing function. MATERIALS AND METHODS: Tongue prostheses were fabricated
      with high-temperature vulcanizing silicone and heat-polymerizing acrylic to
      restore the functions affected after surgical resection of tongue. Patient's
      speech was evaluated with Dr Speech software version 4. The speech software was
      used to assess different speech parameters such as maximum phonation time,
      fundamental frequency, intensity, jitter, and shimmer. Deglutition assessment was
      done subjectively by using a standardized questionnaire designed by the speech
      pathologist. Speech was recorded for assessment before prosthetic rehabilitation
      and 2 weeks after delivery of the tongue prosthesis. RESULTS: After analysis of
      various speech parameters frequency range was improved with prosthesis (ie,
      172.19 Hz) as compared to without prosthesis (ie, 111.47 Hz). Speech
      intelligibility was improved with tongue prosthesis. Deglutition assessment
      revealed that patient's deglutition abilities were improved. CONCLUSION: Tongue
      prosthesis helps to improve speech and articulation in patients with total
      glossectomy. Apart from that deglutition capability is also significantly
      improved. CLINICAL IMPLICATIONS: Total glossectomy affects speech, mastication,
      and swallowing to a greater proportion. It may also lead to psychological
      impairment of the patient. Tongue prosthesis efficiently improves speech and
      deglutition abilities of the patient leading to a better quality of life.

PMID- 29023299
TI  - Reconstruction of Liposarcoma Resection Defect With a Made-to-Measure
      Polyethylene Prosthesis Using Three-Dimensional Digital Technology.
AB  - BACKGROUND: Liposarcoma is considered one of the most frequently occurring tumors
      of the soft tissues, representing 17% to 30% of all mesenchymal cell tumors. It
      is less common in the head and neck representing <10% of tumors in this region.
      The reconstruction of defects derived from resection of these tumors presents a
      surgical challenge. New three-dimensional digital technologies allow more exact
      surgery, cause less morbidity, and achieve adequate aesthetic outcomes.
      OBJECTIVE: The aim of this article was to describe the complex reconstruction of
      a defect caused by the resection of a liposarcoma in the temporal region.
      METHODS: Three-dimensional technology allowed patient planning and a
      reconstruction that was as exact as possible. A made-to-measure polymethyl
      methacrylate prosthesis was used to correct the defect in the zygomatic arch. The
      temporal fossa was covered with a standard porous polyethylene prosthesis.
      CONCLUSIONS: Satisfactory esthetic and functional results were achieved using
      three-dimensional digital technology for treatment planning and to fabricate a
      made-to-measure polyethylene prosthesis and surgical guide.

PMID- 29023300
TI  - Thyroglossal Duct Cyst at the Base of Tongue: The Emerging Role of Transoral
      Endoscopic-Assisted Surgery.
AB  - Cystic lesions involving the tongue base are rare, generally presenting in
      pediatric patients, and they may encompass different pathologies such as ranula,
      lingual ectopic thyroid, thyroglossal duct cyst (TDC), dysontogenetic cysts,
      benign, and malignant tumors.This paper describes the case of a 19-year-old girl
      with phonation impairment and mild dysphagia due to limited tongue protrusion and
      movements. Radiologic examinations revealed a bulky cystic lesion at the base of
      tongue with displacement of extrinsic lingual muscles. A minimally invasive
      transoral removal of the mass was performed under the assistance of the
      endoscopic system. The histopathologic analysis confirmed the diagnosis of
      intralingual TDC. After 2 years of clinical and radiologic follow-up, no
      recurrence of disease was observed and the patient is completely asymptomatic.The
      present experience suggests that the endoscopic-assisted transoral removal of
      intralingual TDC can be proposed as a safe and effective procedure, alternative
      to traditional transcervical surgery as well as to transoral robotic surgery,
      leading to very appealing cosmetic results and encouraging functional outcomes in
      terms of phonation and swallowing. Preoperative radiologic examinations should be
      performed for an accurate diagnosis and appropriate selection of patients.

PMID- 29023301
TI  - Inflammatory Myofibroblastic Tumor: Rare Manifestation in Face.
AB  - Inflammatory myofibroblastic tumor, also known as inflammatory pseudotumor and
      plasma cell granuloma, is a tumor that occurs most often in the lungs, abdomen,
      skin, soft tissue, genital system, and mediastinal. Before surgery, the diagnosis
      is difficult to establish because of its diverse manifestations. In the head and
      neck, manifestation is rare and may occur in the upper respiratory tract, soft
      tissues, orbits, and skull base. This article aims to report a rare manifestation
      of the disease in the face, highlighting the importance of a correct diagnosis to
      determine the most appropriate form of treatment, in male patient, leucoderma, 22
      years old, with complain of a painless unilateral growth in the left cheek,
      beginning 2 months before and with progressive growth.

PMID- 29023302
TI  - Complete Resolution of Lymphoid Interstitial Pneumonia in a Patient With Juvenile
      Myelomonocytic Leukemia Treated With Allogeneic Bone Marrow Transplant: Killing 2
      Birds With 1 Stone.
AB  - Lymphoid interstitial pneumonia (LIP) is a rare disease characterized by benign
      reactive polyclonal proliferation of bronchus-associated lymphoid tissue after
      exposure to inhaled or circulating antigen(s), leading to a disease
      symptomatology similar to idiopathic interstitial pneumonia. Its association with
      diseases that are caused due to immune dysregulation (autoimmune diseases,
      congenital/acquired immunodeficiency, and allogeneic bone marrow transplant) and
      response to immunomodulatory/suppressive medications suggests an immunologic
      pathophysiology. Although LIP has been reported in association with
      lymphoproliferative diseases like Castleman disease, it has never been described
      in patients with leukemia. We report the first case of LIP in a patient with
      juvenile myelomonocytic leukemia (JMML) who was found to have a novel germline
      mutation of unknown significance in additional sex combs-like-1 (ASXL1) gene and
      a pathogenic somatic mutation of protein tyrosine phosphatase, nonreceptor type
      11 (PTPN11) gene at diagnosis. The patient underwent a matched unrelated bone
      marrow transplant for JMML with complete resolution of JMML and LIP with no
      recurrence to date. We also emphasize the importance of considering LIP in
      differential diagnosis of pulmonary lesions seen in conjunction with hematologic
      malignancies and distinguishing it from malignant infiltration of the lung.

PMID- 29023303
TI  - Test-Retest Reliability of an Experienced Global Trigger Tool Review Team.
AB  - OBJECTIVES: During a comprehensive patient safety program at a 550-bed regional
      hospital in the Capital Region of Denmark, we observed an unexpected and
      unexplained doubling of the median patient harm rate from 56 to 109 harms per
      1000 patient days measured by the Institute for Healthcare Improvement Global
      Trigger Tool (GTT). Meanwhile, other measures of patient safety, including
      hospital standardized mortality ratio, were stable or improving. Moreover, the
      review team was very experienced and stable during this period. Thus, we
      hypothesized that the increase in harm rate was not a true reflection of
      increased risk of patient harm but the result of the team getting better at
      identifying harms during GTT reviews. METHODS: We examined the ability of the GTT
      review team to reproduce the rate of harm of two separate periods in the same
      hospital: period 1 (January-June 2010) and period 2 (October 2011-March 2012).
      For each period, we examined two samples: the original sample that was drawn and
      used for the ongoing monitoring of harm at the hospital during the safety
      campaign and a second that we drew and analyzed for this study. RESULTS: We found
      increased harm rates both between review 1 and review 2 and between period 1 and
      period 2. The increase was solely in category E, minor temporary harm.
      CONCLUSIONS: The very experienced GTT team could not reproduce harm rates found
      in earlier reviews. We conclude that GTT in its present form is not a reliable
      measure of harm rate over time.

PMID- 29023304
TI  - Association of Insulin and Cholesterol Levels With Peripheral Nervous System
      Function in Overweight Adults: A 3-Year Follow-up.
AB  - PURPOSE: The purpose of this prospective 3-year follow-up was to investigate the
      association of glucose, insulin, and cholesterol levels with peripheral nervous
      system function in overweight and obese subjects. METHODS: Forty nondiabetic
      overweight and obese adults were enrolled, of whom 29 completed the follow-up.
      Peripheral nervous system function was measured and defined by conduction studies
      of the peroneal motor nerve and the radial, sural, and medial plantar sensory
      nerves. Serum insulin and glucose levels were determined with an oral glucose
      tolerance test, and cholesterol levels were measured. The measurements were
      performed at baseline and after 3 years. RESULTS: The change in serum insulin
      level at 120 minutes after an oral glucose tolerance test was positively
      associated with changes in peroneal nerve conduction velocities and F-wave mean,
      sural nerve conduction and medial plantar nerve conduction velocities. Action
      potential amplitudes decreased consistently and significantly in all sensory
      nerves. CONCLUSIONS: The change in serum insulin level at 120 minutes appears to
      be positively associated with changes in nerve conduction velocities more than 3
      years but not with nerve action potential amplitudes. Significant decreases in
      the action potential amplitudes of all sensory nerves suggest that such changes
      might be the earliest detectable sign of damage to the peripheral nervous system
      in overweight and obese people without type 2 diabetes.

PMID- 29023305
TI  - Insights Into the Therapeutic Effect of Responsive Neurostimulation Assessed With
      Scalp EEG Recording: A Case Report.
AB  - The responsive neurostimulation system (RNS) is the first closed-loop
      neurostimulator approved as an adjunctive treatment for adults with medically
      refractory focal epilepsy from no more than two seizure foci. In addition to its
      therapeutic effect, it provides chronic intracranial EEG recordings, with limited
      storage capacity. Long-term monitoring with scalp EEG recordings can provide
      additional information regarding seizure patterns, the efficacy of RNS
      stimulation in aborting individual seizures, and the net effect of RNS on seizure
      control. We present a 34-year-old woman with medically intractable right
      temporoparietal lobe epilepsy who failed two resective epilepsy surgeries and MR
      guided laser interstitial thermal therapy (MRgLITT), after which RNS was
      implanted. Long-term scalp EEG performed 16 months after implantation showed
      continuous right hemisphere slowing and right temporal sharp waves. In addition,
      RNS stimulation produced bursts of high-voltage, broad-field, surface-negative
      activity, which allowed correlation of RNS stimulation with scalp EEG patterns.
      Twenty-seven seizures were captured. Responsive neurostimulation system
      stimulation did not abort any of the seizures recorded on the scalp EEG. However,
      the frequency of seizures doubled after RNS stimulation was discontinued and
      returned to baseline once it was turned back on. This observation supports the
      neuromodulation effect of RNS.

PMID- 29023306
TI  - Medical Error Avoidance in Intraoperative Neurophysiological Monitoring: The
      Communication Imperative.
AB  - Error avoidance in medicine follows similar rules that apply within the design
      and operation of other complex systems. The error-reduction concepts that best
      fit the conduct of testing during intraoperative neuromonitoring are forgiving
      design (reversibility of signal loss to avoid/prevent injury) and system
      redundancy (reduction of false reports by the multiplication of the error rate of
      tests independently assessing the same structure). However, error reduction in
      intraoperative neuromonitoring is complicated by the dichotomous roles (and
      biases) of the neurophysiologist (test recording and interpretation) and surgeon
      (intervention). This "interventional cascade" can be given as follows: test ->
      interpretation -> communication -> intervention -> outcome. Observational and
      controlled trials within operating rooms demonstrate that optimized
      communication, collaboration, and situational awareness result in fewer errors.
      Well-functioning operating room collaboration depends on familiarity and trust
      among colleagues. Checklists represent one method to initially enhance
      communication and avoid obvious errors. All intraoperative neuromonitoring
      supervisors should strive to use sufficient means to secure situational awareness
      and trusted communication/collaboration. Face-to-face audiovisual teleconnections
      may help repair deficiencies when a particular practice model disallows personal
      operating room availability. All supervising intraoperative neurophysiologists
      need to reject an insular or deferential or distant mindset.

PMID- 29023308
TI  - Considerations About "Carpal Tunnel Syndrome Grading Using High-Resolution
      Ultrasonography".

PMID- 29023309
TI  - Reply to Considerations About "Carpal Tunnel Syndrome Grading Using High
      Resolution Ultrasonography".

PMID- 29023310
TI  - Lid-Parallel Conjunctival Folds and Their Ability to Predict Dry Eye.
AB  - PURPOSE: The observation of lid-parallel conjunctival folds (LIPCOF) is reported
      to be useful in dry eye diagnoses. Around 70% of the European clinicians use this
      test in a dry eye clinic. This study investigated the sensitivity and specificity
      of LIPCOF to predict dry eye. METHODS: Ocular Surface Disease Index (OSDI)
      outcome, noninvasive break-up time (NIKBUT) using the Keratograph (Oculus,
      Wetzlar, Germany), and LIPCOF of 148 randomized selected patient reports (88
      females; mean age=37.0+/-12.9 years) from 3 different sites were analyzed.
      Subjects were divided into dry eye and non-dry eye groups by OSDI only, named
      symptomatic dry eye (OSDI scores >=15) and by a composite score (OSDI scores >=15
      and NIKBUTaverage of <=9 sec). RESULTS: Lid-parallel conjunctival folds
      (temporal, nasal, Sum [=temporal+nasal]) were significantly correlated to OSDI
      and to NIKBUTaverage (Spearman; r>-0.185, P<0.013). NIKBUTaverage (r=-0.322;
      P<0.001) was significantly correlated to OSDI scores. Based on the OSDI
      questionnaire, 37.2% of the subjects were symptomatic and 14.7% were positive for
      dry eye based on the composite score. Lid-parallel conjunctival folds were a
      significant discriminator between healthy and dry eye subjects (P<=0.001). The
      areas under the receiver operating characteristic curve for temporal LIPCOF,
      nasal LIPCOF, and LIPCOF Sum were 0.716, 0.737, and 0.771, respectively, for the
      symptomatic dry eye group and 0.771, 0.719, and 0.798, respectively, for the
      composite dry eye group. CONCLUSIONS: As LIPCOF demonstrated high predictive
      ability of dry eye; it appears to be a promising test in the diagnoses of dry
      eye.

PMID- 29023307
TI  - Interrater Agreement of EEG Interpretation After Pediatric Cardiac Arrest Using
      Standardized Critical Care EEG Terminology.
AB  - PURPOSE: We evaluated interrater agreement of EEG interpretation in a cohort of
      critically ill children resuscitated after cardiac arrest using standardized EEG
      terminology. METHODS: Four pediatric electroencephalographers scored 10-minute
      EEG segments from 72 consecutive children obtained 24 hours after return of
      circulation using the American Clinical Neurophysiology Society's (ACNS)
      Standardized Critical Care EEG terminology. The percent of perfect agreement and
      the kappa coefficient were calculated for each of the standardized EEG variables
      and a predetermined composite EEG background category. RESULTS: The overall
      background category (normal, slow-disorganized, discontinuous, or attenuated
      featureless) had almost perfect agreement (kappa 0.89).The ACNS Standardized
      Critical Care EEG variables had agreement that was (1) almost perfect for the
      seizures variable (kappa 0.93), (2) substantial for the continuity (kappa 0.79),
      voltage (kappa 0.70), and sleep transient (kappa 0.65) variables, (3) moderate
      for the rhythmic or periodic patterns (kappa 0.55) and interictal epileptiform
      discharge (kappa 0.60) variables, and (4) fair for the predominant frequency
      (kappa 0.23) and symmetry (kappa 0.31) variables. Condensing variable options led
      to improved agreement for the continuity and voltage variables. CONCLUSIONS:
      These data support the use of the standardized terminology and the composite
      overall background category as a basis for standardized EEG interpretation for
      subsequent studies assessing EEG background for neuroprognostication after
      pediatric cardiac arrest.

PMID- 29023311
TI  - Comparison of Extended Depth-of-Focus Prototype Contact Lenses With the 1-Day
      ACUVUE MOIST MULTIFOCAL After One Week of Wear.
AB  - OBJECTIVES: To compare visual performance of extended depth-of-focus (EDOF)
      prototypes with a new, center-near, commercial, multifocal contact lens. METHODS:
      Presbyopic participants (n=57) wore 1-Day ACUVUE MOIST MULTIFOCAL (1DAMM) and an
      EDOF prototype for one week in a double-masked, prospective, cross-over,
      randomized clinical trial. Manufacturers' guide was used to select the first pair
      of lens to be fit based on subjective distance refraction and near addition.
      After one week, high- and low-contrast visual acuities were measured at distance
      (6 m), intermediate (70 cm) and near (50 and 40 cm), and stereopsis at 40 cm.
      Subjective performance was assessed on a 1 to 10 numeric rating scale for vision
      clarity and lack of ghosting at distance, intermediate and near, vision
      stability, haloes at night time, overall vision satisfaction, and ocular comfort.
      Linear mixed models were used for analysis and the level of significance was set
      at 5%. RESULTS: 1DAMM was not significantly different from EDOF for high- or low
      contrast visual acuity at any distance, or for stereopsis. Subjectively, EDOF was
      significantly better than 1DAMM for vision clarity at intermediate (P=0.033) and
      near (P<0.001), overall lack of ghosting (P=0.012), vision stability (P=0.004),
      and overall vision satisfaction (P=0.005). For all other subjective variables,
      there were no differences between EDOF and 1DAMM (P>0.05). CONCLUSIONS: EDOF
      prototype lenses offer improvements over the newly marketed 1DAMM lenses for
      several subjective variables.

PMID- 29023312
TI  - Prediction of Descemet Membrane Perforation During Deep Anterior Lamellar
      Keratoplasty in Patients With Keratoconus With Stromal Scar.
AB  - OBJECTIVES: To report big-bubble deep anterior lamellar keratoplasty (DALK) in
      patients with keratoconus with corneal stromal scar, and to investigate factors
      that can influence intraoperative Descemet membrane (DM) perforation. METHODS: A
      retrospective study included patients with keratoconus with central stromal scar
      that underwent DALK using the big-bubble technique. Best spectacle-corrected
      visual acuity (BSCVA), keratometry, minimum corneal thickness (MCT), stromal scar
      depth, and endothelial cell density (ECD) were recorded. Receiver operating
      characteristic (ROC) curves were analyzed to predict an intraoperative
      perforation related to stromal scar. RESULTS: Thirty-eight eyes of 38 patients
      with keratoconus (mean age: 30.0+/-9.2 years) were included in this study. Thirty
      four eyes had successful DALK; in four eyes, the procedure was converted to
      penetrating keratoplasty because of DM macroperforations. Successful big-bubble
      formation was achieved in 24 of 38 (63.2%) eyes, whereas in 10 eyes, manual
      dissection was used to complete the DALK. Mean preoperative and postoperative
      second year BSCVA were 1.3 (+/-0.4) and 0.5 (+/-0.2) logarithm of the minimum
      angle of resolution (P<0.001), keratometry values were 65.5+/-7.4 and 42.8+/-7.8
      diopters (P<0.001), and ECD were 2,740+/-359 and 2,279+/-452 cells/mm (P<0.001),
      respectively. Using ROC analysis, the area under curve value to predict DM
      perforation was found to be 0.792 (scar/MCT ratio, P=0.04) and the best cutoff
      point for scar depth/MCT ratio was 53%. CONCLUSION: Big-bubble DALK is effective
      in patients with keratoconus with stromal scars. Scar depth/MCT ratio seems to
      predict the DM perforation.

PMID- 29023313
TI  - Mini-Scleral Lenses for Correction of Refractive Errors After Radial Keratotomy.
AB  - OBJECTIVE: To evaluate the factors affecting clinical outcomes of correcting
      cumulative refractive errors or irregular astigmatism after radial keratotomy
      (RK) using mini-scleral lenses. METHODS: We retrospectively analyzed 36 eyes
      receiving mini-scleral lenses after RK from July 2011 to June 2016. Analyses
      included age, refractive errors, best spectacle-corrected visual acuity (BSCVA),
      best contact lens-corrected visual acuity (BCLCVA), topographic indices, RK
      treatment zone diameter (TZD), power difference (PrD) within the RK treatment
      zone, and decentration distance (DD) of the RK treatment zone center. An increase
      of three lines or more of Snellen visual acuity was considered a successful
      fitting. RESULTS: Of the eyes fitted with mini-scleral lenses, the BCLCVA
      (logarithm of the minimum angle of resolution [logMAR] 0.19+/-0.22) was
      significantly better than the BSCVA (logMAR 0.47+/-0.30). Twenty-three patients
      (64%) had a successful fitting. There was no statistically significant difference
      between successful and unsuccessful fittings with regard to age, prefitting
      refractive error, BSCVA, corneal astigmatism, simulated steep/flat K values,
      surface regularity index, TZD, or PrD. However, successful fittings had better
      centration of treatment zones with an average DD of 0.54+/-0.44 mm compared with
      a DD of 0.92+/-0.53 mm in the unsuccessfully fitted eyes. In addition, our case
      series showed that there was a negative impact on fitting outcomes in the
      presence of small central clear zones resulting from central incisions or scars.
      CONCLUSIONS: Although decentration of the RK treatment zone and small central
      clear zones were related to less optimal fitting results, mini-scleral lenses are
      a feasible option to correct cumulative refractive errors and irregular
      astigmatism in post-RK patients.

PMID- 29023314
TI  - Renal dysfunction and cirrhosis.
AB  - PURPOSE OF REVIEW: Hepatorenal syndrome (HRS) does not represent the predominant
      phenotype of acute kidney injury (AKI) in cirrhosis. Early recognition of HRS
      helps initiate appropriate therapy. The aims of this review are to present
      redefinition of AKI, to list new biomarkers, to report recent data on
      vasopressors in HRS and to propose criteria for simultaneous liver and kidney
      transplantation (SLKT). RECENT FINDINGS: Urine output, which was not part of the
      definition of AKI might be reconsidered as it has an independent prognostic
      value. Biomarkers (NGAL and IL-18) could help identify ATN. However, cut-off
      values have to be clarified. Vasopressors with albumin represent first option in
      HRS. Continuous infusion of terlipressin has a better safety profile than
      intravenous boluses. SLKT should be considered whenever native kidney recovery is
      unlikely [i.e. prolonged renal replacement therapy (RRT) and/or GFR less than 25
      ml/min for 6 weeks prior to transplantation]. SUMMARY: New definitions and recent
      biomarkers may help differentiate HRS from ATN at an earlier stage. Urine output
      should be reconsidered in the definitions. Even in patients who are not
      candidates for transplantation, a short trial of RRT is justified whenever
      needed. SLKT should be considered whenever posttransplant renal recovery is
      unlikely.

PMID- 29023315
TI  - Biomarkers of drug-induced kidney injury.
AB  - PURPOSE OF REVIEW: Drug-induced kidney injury (DIKI) is an important and
      potentially modifiable cause of acute kidney injury (AKI). The reliance on
      traditional markers of kidney injury to diagnose DIKI impedes early detection.
      Biomarkers of DIKI that facilitate early diagnosis and the identification of high
      risk patients are essential to ameliorate the clinical burden of this
      complication. RECENT FINDINGS: Recent progress in this area supports the
      potential utility of several biomarkers for the diagnosis of DIKI, for the
      prediction of outcomes and also for monitoring responses to potential nephrotoxic
      or beneficial therapies. Data regarding the impact of clinically relevant
      factors, such as chronic kidney disease, on biomarker levels represents a further
      recent advancement. Emerging novel biomarkers include microRNAs, which are
      showing promise as markers of drug-induced tubular damage. They may also have a
      role in elucidating the molecular mechanisms of AKI. SUMMARY: There is compelling
      evidence to support the use of biomarkers for the early detection of DIKI.
      Ongoing research is required to delineate their role in prognostication and for
      the prediction of outcomes. The inclusion of biomarkers in more clinical studies
      of DIKI would be a welcome advance, which may accelerate their integration into
      clinical diagnostics.

PMID- 29023316
TI  - Septic shock resuscitation in the first hour.
AB  - PURPOSE OF REVIEW: We reviewed the recent advances in the initial approach to
      resuscitation of sepsis and septic shock patients. RECENT FINDINGS: Sepsis and
      septic shock are life-threatening emergencies. Two key interventions in the first
      hour include timely antibiotic therapy and resuscitation. Before any laboratory
      results, the need for resuscitation is considered if a patient with suspected
      infection has low blood pressure (BP) or impaired peripheral circulation found at
      clinical examination. Until now, this early resuscitation in sepsis and septic
      shock was supported by improvements in outcome seen with goal-directed therapy.
      However, three recent, goal-directed therapy trials failed to replicate the
      originally reported mortality reductions, prompting a debate on how this early
      resuscitation should be performed. As resuscitation is often focussed on
      macrociculatory goals such as optimizing central venous pressure, the discordance
      between microcirculatory and macrocirculatory optimization during resuscitation
      is a potential argument for the lack of outcome benefit in the newer trials.
      Vasoactive drug dose and large volume resuscitation-associated-positive fluid
      balance, are independently associated with worse clinical outcomes in critically
      ill sepsis and septic shock patients. As lower BP targets and restricted volume
      resuscitation are feasible and well tolerated, should we consider a lower BP
      target to reduce the adverse effects of catecholamine' and excess resuscitation
      fluids. Evidence guiding fluids, vasopressor, and inotrope selection remains
      limited. SUMMARY: Though the early resuscitation of sepsis and septic shock is
      key to improving outcomes, ideal resuscitation targets are elusive. Distinction
      should be drawn between microcirculatory and macrocirculatory changes, and
      corresponding targets. Common components of resuscitation bundles such as large
      volume resuscitation and high-dose vasopressors may not be universally
      beneficial. Microcirculatory targets, individualized resuscitation goals, and
      reassessment of completed trials using the updated septic shock criteria should
      be focus areas for future research.

PMID- 29023317
TI  - Effects of physical exercise in older adults with reduced physical capacity: meta
      analysis of resistance exercise and multimodal exercise.
AB  - Older adults with reduced physical capacity are at greater risk of progression to
      care dependency. Progressive resistance strength exercise and multimodal exercise
      have been studied to restore reduced physical capacity. To summarize the best
      evidence of the two exercise regimes, this meta-analysis study appraised
      randomized-controlled trials from published systematic reviews. Medline, Embase,
      and the Cochrane Database of Systematic Review and Cochrane Central Register of
      Controlled Clinical Trials were searched for relevant systematic reviews. Two
      reviewers independently screened the relevant systematic reviews to identify
      eligible trials, assessed trial methodological quality, and extracted data.
      RevMan 5.3 software was used to analyze data on muscle strength, physical
      functioning, activities of daily living, and falls. Twenty-three eligible trials
      were identified from 22 systematic reviews. The mean age of the trial
      participants was 75 years or older. Almost all multimodal exercise trials
      included muscle strengthening exercise and balance exercise. Progressive
      resistance exercise is effective in improving muscle strength of the lower
      extremity and static standing balance. Multimodal exercise is effective in
      improving muscle strength of the lower extremity, dynamic standing balance, gait
      speed, and chair stand. In addition, multimodal exercise is effective in reducing
      falls. Neither type of exercise was effective in improving activities of daily
      living. For older adults with reduced physical capacity, multimodal exercise
      appears to have a broad effect on improving muscle strength, balance, and
      physical functioning of the lower extremity, and reducing falls relative to
      progressive resistance exercise alone.

PMID- 29023318
TI  - Comparison of gut-directed hypnotherapy and unspecific hypnotherapy as self-help
      format in children and adolescents with functional abdominal pain or irritable
      bowel syndrome: a randomized pilot study.
AB  - OBJECTIVE: Psychosocial treatments for chronic abdominal pain in childhood or
      adolescence are effective, but time consuming and hardly available. In the
      present study, gut-directed hypnotherapy (GDHT) and unspecific hypnotherapy (UHT)
      were compared to evaluate the feasibility and efficacy of a hypnotherapeutic self
      help intervention. PARTICIPANTS AND METHODS: Children/adolescents between 6 and
      17 years of age with chronic abdominal pain were randomized to GDHT or UHT. The
      treatment period was 12 weeks each. Measurements were performed before and after
      treatment. The primary outcome was a pain diary. Analysis was carried out as per
      protocol. RESULTS: Of 45 participants included, 13 were lost to follow-up. Thirty
      two participants (14 GHDT, 18 UHT) were analyzed. Dropouts had higher pain
      severity. Completers in both conditions showed good adherence and a similar
      decrease in days with pain and pain duration. Pain intensity decreased only in
      the UHT condition. Eleven participants (two GDHT, nine UHT) achieved clinical
      remission (>80% improvement) and 13 participants (seven GDHT, six UHT) improved
      significantly (30-80%). CONCLUSION: Results suggest a high efficacy of
      standardized home-based hypnotherapy for children/adolescents with abdominal
      pain. Children/adolescents with high pain severity are at risk of dropping out.
      The UHT condition showed slight evidence of superiority, but conditions were
      equivalent on most outcomes. Taken together, self-help approaches based on
      hypnotherapy could close a treatment gap and prevent chronification.

PMID- 29023319
TI  - Comparison of fenofibrate and pioglitazone effects on patients with nonalcoholic
      fatty liver disease.
AB  - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is known to be a health
      related problem; there is no proven treatment for NAFLD. However, a wide range of
      possible therapies have been proposed and studied. In the current study, we aimed
      to compare the therapeutic effects of fenofibrate and pioglitazone on NAFLD.
      PATIENTS AND METHODS: In this randomized clinical trial study (ethic number:
      ZUMS.REC.1393.133), patients with NAFLD and alanine aminotransferase in range of
      1-1.5 folds of normal and BMI (25-35) were studied. Blood lipids and liver
      enzymes were measured. The patients were divided randomly into three groups
      (recipient of fenofibrate, pioglitazone, and exercise). After the patients
      completed the course of treatment, liver enzymes were measured. RESULTS:
      According to the results of this study, 90 patients with NAFLD were divided into
      three groups of 30 patients. All variables at the beginning of the study showed
      no significant difference among the three groups, but after the treatment period,
      the results showed that the levels of alanine aminotransferase, aspartate
      transaminase, systolic blood pressure, diastolic blood pressure, and BMI changed
      significantly: the levels decreased in all groups. CONCLUSION: This study showed
      beneficial effects of fenofibrate and pioglitazone in patients with fatty liver.
      Further studies with larger study populations on the effects of these drugs on
      fatty liver, lipid profile, blood glucose, and insulin are suggested.

PMID- 29023320
TI  - Favorable liver cancer mortality-to-incidence ratios of countries with high
      health expenditure.
AB  - OBJECTIVE: Health expenditure is a marker associated with an advanced healthcare
      system, which contributes toward the good prognosis of patients. Mortality-to
      incidence ratios (MIRs) are one of the predictors that reflect the prognosis of
      cancer patients. There remains some uncertainty on the correlation of MIRs of
      liver cancer with the health expenditure of countries. METHODS: We therefore
      analyzed the correlation of MIRs from the GLOBOCAN 2012 database with the WHO
      rankings and the total expenditures on health/gross domestic product from WHO by
      linear regression analyses. A total of 29 countries were selected in this study
      according to the data quality and the incidence number. RESULTS: The results
      showed high rates of incidence/mortality and MIRs in less developed regions (0.92
      vs. 0.96 for more vs. less developed regions). Among the continents, Asia has the
      highest incidence/mortality in case number, crude rate, and age-standardized
      rate. In terms of the MIR, Northern America has the lowest MIR and Latin America
      and the Caribbean have the highest MIRs (0.82 and 1.04, respectively). Finally,
      favorable MIRs are associated significantly with good WHO ranking and high
      expenditures on gross domestic product (P=0.048 and 0.025, respectively).
      CONCLUSION: The MIR variation for liver cancer is thus found to be associated
      with the health expenditure and WHO ranking.

PMID- 29023321
TI  - Antipsychotic medication and oropharyngeal dysphagia: systematic review.
AB  - The association between antipsychotics (also known as neuroleptics) and
      oropharyngeal dysphagia (OD) has been suggested in several case reports. The
      purpose of this systematic review was to examine the effect of antipsychotic
      medication on OD. A systematic literature search was carried out according to
      PRISMA guidelines using the electronic databases Pubmed and Embase. In Pubmed, we
      used the MeSH terms 'antipsychotic agents' OR 'tranquilizing agents' combined
      with 'deglutition disorders' OR 'deglutition'. In Embase, we used the Emtree
      terms 'neuroleptic agents' combined with 'swallowing' OR 'dysphagia'. Two
      reviewers assessed the eligibility of each report independently. The level of
      evidence of the included studies was also assessed according to pre-established
      criteria. Case reports were excluded. We found 18 clinical studies of dysphagia
      related to antipsychotics: 12 were related both to typical and atypical
      antipsychotics, four to atypical antipsychotics and two to typical
      antipsychotics. According to the clinical studies included, prevalence of
      patients with swallowing problems taking antipsychotics ranged from 21.9 to 69.5%
      whereas prevalence of patients without swallowing problems taking antipsychotics
      ranged from 5 to 30.5%. The available evidence suggests considering an etiology
      of dysphagia in patients with swallowing problems who are taking antipsychotics,
      even if no other symptoms are present. Although few general conclusions can be
      drawn from current evidence, both typical and atypical antipsychotics can be
      associated with OD.

PMID- 29023322
TI  - Effects of Two Different Training Periodization Models on Physical and
      Physiological Aspects of Elite Female Team Handball Players.
AB  - Manchado, C, Cortell-Tormo, JM, and Tortosa-Martinez, J. Effects of two different
      training periodization models on physical and physiological aspects of elite
      female team handball players. J Strength Cond Res 32(1): 280-287, 2018-The aim of
      this study was to compare training-induced changes in selected physiological and
      physical team handball performance factors after 2 training periodization models:
      traditional periodization (TP) vs. block periodization (BP). Eleven female team
      handball players who played over 2 consecutive seasons for a Spanish first league
      team were assessed twice per season during a training cycle. On each occasion,
      participants completed anthropometric, maximal strength, and lower-body power
      assessments. In addition, incremental tests to determine maximum oxygen uptake
      (V[Combining Dot Above]O2max), sprint- and sport-specific throwing velocity tests
      were performed. Block periodization group experienced significantly greater
      improvements than TP on squat jump (5.97%; p < 0.001), countermovement jump
      (8.76%; p = 0.011), hand-grip strength (8.22%; p = 0.029), bench press 1
      repetition maximum (1RM) (5.14%; p = 0.049), 10-m sprint (-6.19%; p < 0.001), and
      20-m sprint (2.95%; p = 0.008). Greater changes in BP group (p <= 0.05) were also
      found for the throwing velocities in sport-specific tests compared with the TP
      group. No significant difference between the groups were detected for the half
      squat 1RM (p = 0.15) and the V[Combining Dot Above]O2max (p = 0.44). These
      findings suggest that BP may be more effective than TP for improving important
      physiological and physical team handball performance factors in high level female
      handball players.

PMID- 29023323
TI  - Optimizing inter-session reliability of heart rate variability - the effects of
      artefact correction and breathing type.
AB  - This study aimed to comprehensively investigate the reliability of multiple heart
      rate variability (HRV) parameters, and to explore the influence of artefact
      removal and breathing condition on HRV reliability. Resting HRV was collected
      using Polar Team monitors on forty-one participants (age: 19.9+/-1.2 years; 28
      females, 13 males) during two separate days. Within each session, participants
      performed 10 minutes each of spontaneous and controlled breathing (randomized
      order). Kubios HRV analysis software was used to analyze 180s data epochs using
      "low" or "strong" artefact removal. Relative reliability was assessed using
      intraclass correlation coefficients (ICC2,1) and absolute reliability was
      quantified using mean-normalized standard error of measurement (SEM%). Time
      domain and nonlinear parameters produced poor to good inter-session agreement
      (ICC:0.34-0.68; SEM%: 11.0-39.0) with "low" artefact removal, regardless of
      breathing condition. Frequency domain parameters demonstrated fair inter-session
      agreement during controlled breathing (ICC:0.40-0.45; SEM%: 26.0-70.0), but poor
      agreement during spontaneous breathing (ICC:0.07-0.13; SEM%: 32.0-81.0). Minimal
      differences in ICCs were observed between "low" and "strong" artefact removal.
      Thus, this study provides three practical applications: 1) HRV monitoring is most
      reliable when using time domain and nonlinear parameters, regardless of breathing
      or filtering condition, but no single parameter is especially reliable. The large
      variation and poor inter-session reliability of frequency indices during
      spontaneous breathing are improved by controlling breathing rate; 2) "Low"
      artefact removal appears superior to more aggressive artefact removal; and 3)
      Inter-session differences in HRV measurements <30% may be indicative of normal
      daily variation rather than true physiologic changes.

PMID- 29023324
TI  - The physical response to a simulated period of soccer-specific fixture
      congestion.
AB  - The aim of this study was to assess the physiological, perceptual, and mechanical
      measures associated with the completion of a simulated period of short-term
      soccer-specific fixture congestion. Ten male semi-professional soccer players
      completed three trials of a treadmill-based match simulation, with 48 hours
      intervening each trial. A repeated measures general linear model identified
      significantly (P= 0.02) lower knee flexor peak torque (PT) recorded at 300
      degs[BULLET OPERATOR]s in the second (141.27 +/- 28.51 Nm) and third trials
      (139.12 +/- 26.23 Nm) when compared to the first (154.17 +/- 35.25 Nm).
      Similarly, muscle soreness (MS) and PT data recorded at 60 degs[BULLET OPERATOR]s
      were significantly (P< 0.05) different in the third trial (MS= 42 +/- 25 a.u;
      PT60= 131.10 +/- 35.38 Nm) when compared to the first (MS= 29 +/- 29 a.u; PT60=
      145.61 +/- 42.86 Nm). Significant (P= 0.003) differences were also observed for
      mean Bicep Femoris electromyography (EMGmean) between the third trial (T0-15=
      126.36 +/- 15.57 uV; T75-90= 52.18 +/- 17.19 uV) and corresponding time points in
      the first trial (T0-15= 98.20 +/- 23.49 uV; T75-90= 99.97 +/- 39.81 uV).
      Cumulative increases in perceived exertion, heart rate, oxygen consumption, blood
      lactate concentrations, EMGmean, and PlayerLoad were recorded across each trial.
      MS and PT were also significantly different post-trial. There were however no
      significant main effects or interactions for the salivary Immunoglobulin A, and
      the medial-lateral PlayerLoad metrics. These data suggest a biomechanical and
      muscular emphasis with residual fatigue, with implications for injury risk and
      the development of recovery strategies.

PMID- 29023325
TI  - Performance and Health Related Characteristics of Male Athletes Using Marijuana.
AB  - The influence of chronic marijuana use on the performance and health of
      physically active individuals has yet to be fully elucidated. The purpose of this
      study was to explore pulmonary function, aerobic and anaerobic fitness, strength,
      serum testosterone, cortisol, C-reactive protein (CRP), Delta-9
      tetrahydrocannibinol (THC), 11-nor-9-carboxy-Delta-9-tetrahydrocannibinol (THC
      COOH), and 11-hydroxy-Delta-9-tetrahydrocannibinol (THC-OH) concentrations in a
      physically active population either using or not using marijuana. Healthy,
      physically active males (N=24) were compared based on their marijuana use status:
      marijuana users (MU; n=12) and non-users (NU; n=12). Statistical analysis
      (p=0.05) revealed no difference between groups for age, body mass, body mass
      index, body fat, forced expiratory volume in 1-second percentage, VO2 max,
      anaerobic power output, strength measures, testosterone or cortisol
      concentrations. Although not statistically significant, MU showed a trend to
      fatigue to a greater percentage of absolute power output than NU from the
      beginning to end of the Wingate Anaerobic Power Assessment (p=0.08, ES=0.75). CRP
      in MU (1.76 +/- 2.81 mg/L) and NU (0.86 +/- 1.49 mg/L) was not significantly
      different (p=0.60), but placed MU at moderate risk and NU at low risk for
      cardiovascular disease. Anaerobic fatigue was the only performance variable to
      show a trend for difference between groups. These results suggest that marijuana
      use in physically active males may not have significant effects on performance;
      however, it may be linked to elevated concentrations of CRP which place users at
      a higher risk for cardiovascular disease.

PMID- 29023326
TI  - Combined effects of static stretching and electrical stimulation on joint range
      of motion and muscle strength.
AB  - The purpose of this study was to examine the effects of the combination of static
      stretching (SS) and electrical stimulation (ES) for 8 weeks on joint range of
      motion (ROM), muscle strength, and muscle architecture. Thirty-one subjects were
      divided into three groups: the SS combined with ES (SS+ES) group, SS group, or
      control group. The SS+ES group performed calf stretching simultaneously with ES
      to the gastrocnemius medialis, while the SS group performed calf stretching only.
      The training regimen consisted of four 30 sec sets of stretching, with 30 sec
      rest intervals, 3 days per week for 8 weeks. The control group did not perform
      any intervention exercise. Before and after training, measurements were taken to
      determine the ankle ROM, plantar flexion one repetition maximum strength, muscle
      thickness, pennation angle, and circumference of the lower leg. The results
      showed that 8 weeks of training led to significant improvements in the ankle ROM
      and muscle thickness in both the SS+ES and SS groups. There were significant
      increases in plantar flexion one repetition maximum strength and pennation angle
      in all three groups. For all parameters, there was no difference between the
      SS+ES and SS groups. These results clarify that 8 weeks of SS improves joint ROM
      and muscle thickness, and show that there is no additional benefit gained by
      combining ES with SS in this particular training regime.

PMID- 29023327
TI  - Sodium bicarbonate supplementation delays neuromuscular fatigue without changes
      in performance outcomes during a basketball match simulation protocol.
AB  - PURPOSE: To investigate the development of neuromuscular fatigue during a
      basketball game simulation and ascertain whether sodium bicarbonate (NaHCO3)
      supplementation attenuates any neuromuscular fatigue that persists. METHODS: Ten
      participants ingested 0.2 g.kg of NaHCO3 (or an equimolar placebo dosage of
      sodium chloride [NaCl]) 90 and 60 minutes prior to commencing a basketball game
      simulation (ALK-T vs PLA-T). Isometric maximal voluntary contractions of the knee
      extensors (MVIC) and potentiated high (100 Hz) and low (10 Hz) frequency doublet
      twitches were recorded before and after each match quarter for both trials. In
      addition, 15 m sprint times and layup completion (%) were recorded during each
      quarter. RESULTS: MVIC, 100 and 10 Hz twitch forces declined progressively in
      both trials (P<0.05) with a less pronounced decrease in MVIC during ALK-T
      (P<0.01). Both 100 and 10 Hz twitch forces were also significantly greater in ALK
      T (P<0.05). 15 m sprint time increased over the course of both trials (~2%,
      P<0.01); however, no significant condition or time effect was found for layup
      completion (P>0.05). CONCLUSION: A basketball simulation protocol induces a
      substantial amount of neuromuscular (reduction in knee extensor MVICs) and
      peripheral fatigue with a concomitant increase in 15 m sprint time over the
      protocol. NaHCO3 supplementation attenuated the rate of fatigue development by
      protecting contractile elements of the muscle fibres. PRACTICAL APPLICATIONS:
      This study provides coaches with information about the magnitude of fatigue
      induced by a simulated basketball game, and provides evidence of the efficacy of
      NaHCO3 in attenuating fatigue.

PMID- 29023328
TI  - Strength and Conditioning Habits of Competitive Distance Runners.
AB  - Blagrove, RC, Brown, N, Howatson, G, and Hayes, PR. Strength and conditioning
      habits of competitive distance runners. J Strength Cond Res XX(X): 000-000, 2017
      Targeted strength and conditioning (S&C) programs can potentially improve
      performance and reduce injury risk factors in competitive runners. However, S&C
      practices of distance runners are unknown. This study aimed to explore S&C
      practices of competitive middle- and long-distance runners and examined whether
      reported frequency of injuries was influenced by training behaviors. One thousand
      eight hundred eighty-three distance runners (>=15 years old) completed an online
      survey. All runners who raced competitively were included in data analysis (n =
      667). Distance runners mainly engaged with S&C activities to lower risk of injury
      (63.1%) and improve performance (53.8%). The most common activities used were
      stretching (86.2%) and core stability exercises (70.2%). Resistance training (RT)
      and plyometric training (PT) were used by 62.5 and 35.1% of runners,
      respectively. Junior (under-20) runners include PT, running drills, and circuit
      training more so than masters runners. Significantly more international standard
      runners engaged in RT, PT, and fundamental movement skills training compared with
      competitive club runners. Middle-distance (800-3,000 m) specialists were more
      likely to include RT, PT, running drills, circuit training, and barefoot
      exercises in their program than longer-distance runners. Injury frequency was
      associated with typical weekly running volume and run frequency. Strength and
      conditioning did not seem to confer a protection against the number of injuries
      the runners experienced. Practitioners working with distance runners should
      critically evaluate the current S&C practices of their athletes, to ensure that
      activities prescribed have a sound evidence-based rationale.

PMID- 29023330
TI  - Heart Rate Variability and Training Load Among National Collegiate Athletic
      Association Division 1 College Football Players Throughout Spring Camp.
AB  - Flatt, AA, Esco, MR, Allen, JR, Robinson, JB, Earley, RL, Fedewa, MV, Bragg, A,
      Keith, CM, and Wingo, JE. Heart rate variability and training load among National
      Collegiate Athletic Association Division 1 college football players throughout
      spring camp. J Strength Cond Res XX(X): 000-000, 2017-The purpose of this study
      was to determine whether recovery of cardiac-autonomic activity to baseline
      occurs between consecutive-day training sessions among positional groups of a
      collegiate football team during Spring camp. A secondary aim was to evaluate
      relationships between chronic (i.e., 4-week) heart rate variability (HRV) and
      training load parameters. Baseline HRV (lnRMSSD_BL) was compared with HRV after
      ~20 hours of recovery before next-day training (lnRMSSDpost20) among positional
      groups composed of SKILL (n = 11), MID-SKILL (n = 9), and LINEMEN (n = 5) with a
      linear mixed model and effect sizes (ES). Pearson and partial correlations were
      used to quantify relationships between chronic mean and coefficient of variation
      (CV) of lnRMSSD (lnRMSSD_chronic and lnRMSSDcv, respectively) with the mean and
      CV of PlayerLoad (PL_chronic and PL_cv, respectively). A position * time
      interaction was observed for lnRMSSD (p = 0.01). lnRMSSD_BL was higher than
      lnRMSSDpost20 for LINEMEN (p < 0.01; ES = large), whereas differences for SKILL
      and MID-SKILL were not statistically different (p > 0.05). Players with greater
      body mass experienced larger reductions in lnRMSSD (r = -0.62, p < 0.01).
      Longitudinally, lnRMSSDcv was significantly related to body mass (r = 0.48) and
      PL_chronic (r = -0.60). After adjusting for body mass, lnRMSSDcv and PL_chronic
      remained significantly related (r = -0.43). The ~20-hour recovery time between
      training sessions on consecutive days may not be adequate for restoration of
      cardiac-parasympathetic activity to baseline among LINEMEN. Players with a lower
      chronic training load throughout camp experienced greater fluctuation in lnRMSSD
      (i.e., lnRMSSDcv) and vice versa. Thus, a capacity for greater chronic workloads
      may be protective against perturbations in cardiac-autonomic homeostasis among
      American college football players.

PMID- 29023329
TI  - Living and Training at 825 m for 8 Weeks Supplemented With Intermittent Hypoxic
      Training at 3,000 m Improves Blood Parameters and Running Performance.
AB  - Wonnabussapawich, P, Hamlin, MJ, Lizamore, CA, Manimmanakorn, N, Leelayuwat, N,
      Tunkamnerdthai, O, Thuwakum, W, and Manimmanakorn, A. Living and training at 825
      m for 8 weeks supplemented with intermittent hypoxic training at 3,000 m improves
      blood parameters and running performance. J Strength Cond Res 31(12): 3287-3294,
      2017-We aimed to investigate the effect of an 8-week low-altitude training block
      supplemented with intermittent hypoxic training, on blood and performance
      parameters in soccer players. Forty university-level male soccer players were
      separated into altitude (n = 20, 825 m) or sea-level (n = 20, 125 m) groups.
      Before (1-2 days ago) and after (1 and 14 days later) training, players were
      asked to give a resting venous blood sample and complete a series of performance
      tests. Compared with sea level, the altitude group increased erythropoietin, red
      blood cell (RBC) count, and hematocrit 1 day after training (42.6 +/- 24.0%, 1.8
      +/- 1.3%, 1.4 +/- 1.1%, mean +/- 95% confidence limits (CL), respectively). By 14
      days after training, only RBC count and hemoglobin were substantially higher in
      the altitude compared with the sea-level group (3.2 +/- 1.8%, 2.9 +/- 2.1%
      respectively). Compared with sea level, the altitude group 1-2 days after
      training improved their 50-m (-2.9 +/- 1.4%) and 2,800-m (-2.9 +/- 4.4%) run
      times and demonstrated a higher maximal aerobic speed (4.7 +/- 7.4%). These
      performance changes remained at 14 days after training with the addition of a
      likely higher estimated V[Combining Dot Above]O2max in the altitude compared with
      the sea-level group (3.2 +/- 3.0%). Eight weeks of low-altitude training,
      supplemented with regular bouts of intermittent hypoxic training at higher
      altitude, produced beneficial performance improvements in team-sport athletes,
      which may increase the viability of such training to coaches and players that
      cannot access more traditional high altitude venues.

PMID- 29023331
TI  - Effects of Plyometric Training on Components of Physical Fitness in Prepuberal
      Male Soccer Athletes: The Role of Surface Instability.
AB  - Negra, Y, Chaabene, H, Sammoud, S, Bouguezzi, R, Mkaouer, B, Hachana, Y, and
      Granacher, U. Effects of plyometric training on components of physical fitness in
      prepuberal male soccer athletes: the role of surface instability. J Strength Cond
      Res 31(12): 3295-3304, 2017-Previous studies contrasted the effects of plyometric
      training (PT) conducted on stable vs. unstable surfaces on components of physical
      fitness in child and adolescent soccer players. Depending on the training
      modality (stable vs. unstable), specific performance improvements were found for
      jump (stable PT) and balance performances (unstable PT). In an attempt to combine
      the effects of both training modalities, this study examined the effects of PT on
      stable surfaces compared with combined PT on stable and unstable surfaces on
      components of physical fitness in prepuberal male soccer athletes. Thirty-three
      boys were randomly assigned to either a PT on stable surfaces (PTS; n = 17; age =
      12.1 +/- 0.5 years; height = 151.6 +/- 5.7 cm; body mass = 39.2 +/- 6.5 kg; and
      maturity offset = -2.3 +/- 0.5 years) or a combined PT on stable and unstable
      surfaces (PTC; n = 16; age = 12.2 +/- 0.6 years; height = 154.6 +/- 8.1 cm; body
      mass = 38.7 +/- 5.0 kg; and maturity offset = -2.2 +/- 0.6 years). Both
      intervention groups conducted 4 soccer-specific training sessions per week
      combined with either 2 PTS or PTC sessions. Before and after 8 weeks of training,
      proxies of muscle power (e.g., countermovement jump [CMJ], standing long jump
      [SLJ]), muscle strength (e.g., reactive strength index [RSI]), speed (e.g., 20-m
      sprint test), agility (e.g., modified Illinois change of direction test
      [MICODT]), static balance (e.g., stable stork balance test [SSBT]), and dynamic
      balance (unstable stork balance test [USBT]) were tested. An analysis of
      covariance model was used to test between-group differences (PTS vs. PTC) at
      posttest using baseline outcomes as covariates. No significant between-group
      differences at posttest were observed for CMJ (p > 0.05, d = 0.41), SLJ (p >
      0.05, d = 0.36), RSI (p > 0.05, d = 0.57), 20-m sprint test (p > 0.05, d = 0.06),
      MICODT (p > 0.05, d = 0.23), and SSBT (p > 0.05, d = 0.20). However,
      statistically significant between-group differences at posttest were noted for
      the USBT (p < 0.01, d = 1.49) in favor of the PTC group. For most physical
      fitness tests (except RSI), significant pre-to-post improvements were observed
      for both groups (p < 0.01, d = 0.55-3.96). Eight weeks of PTS or PTC resulted in
      similar performance improvements in components of physical fitness except for
      dynamic balance. From a performance-enhancing perspective, PTC is recommended for
      pediatric strength and conditioning coaches because it produced comparable
      training effects as PTS on proxies of muscle power, muscle strength, speed,
      agility, static balance, and additional effects on dynamic balance.

PMID- 29023332
TI  - Should T-Tube Drainage be Performed for Choledocholithiasis after Laparoscopic
      Common Bile Duct Exploration? A Systematic Review and Meta-Analysis of Randomized
      Controlled Trials.
AB  - BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) has been verified
      to be a comparatively effective treatment approach for uncomplicated
      choledocholithiasis, and it has been previously proposed that the primary duct
      closure (PDC) technique, in which the bile duct can directly be sutured in only 1
      step compared with the T-tube drainage (TTD), can be deemed a choice after LCBDE;
      however, the conventional TTD performance is controversial in the minimally
      invasive surgery era. On the basis of the above-mentioned point, this meta
      analysis was conducted to assess the different effects between TTD and PDC after
      LCBDE. MATERIALS AND METHODS: In PubMed, EMBASE, and the Cochrane Library,
      literature search was conducted to screen out randomized controlled trials (RCTs)
      to compare PDC with TTD. The analyzed outcome variables included overall
      morbidity, biliary-specific morbidity (retained stones, biliary leak, biliary
      peritonitis), other morbidities, operating time, postoperative hospital stay,
      reintervention (surgery, endoscopy/radiology), and median hospital expenses.
      RESULTS: In this meta-analysis, there are 4 RCTs qualifying for inclusion,
      including 396 patients in all (222 in PDC and 214 in TTD). With respect to
      postoperative overall morbidity (P<0.05), biliary peritonitis (P<0.05), surgery
      time (P<0.05), length of stay (P<0.05), and median hospital expenses (P<0.05),
      PDC presented remarkably better results than TTD (P<0.05). Statistically, no
      remarkable distinction was found between the 2 groups as to biliary-specific
      morbidity, retained stones, biliary leak, other morbidities, or reintervention
      (radiology/endoscopy, surgery). CONCLUSIONS: In this meta-analysis, there was no
      evidence provided for clinical benefits of using TTD after LCBDE. Therefore, TTD
      should not routinely be performed after LCBDE. However, multicenter, large sample
      size, RCTs should be conducted to clarify this issue.

PMID- 29023333
TI  - Clinical Indicators of Postoperative Bleeding in Bariatric Surgery.
AB  - The purpose of this study was to evaluate the relationship between patient,
      clinical and laboratory characteristics, and bleeding after bariatric surgery. A
      retrospective chart review was performed for all patients, who underwent a
      laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy at our
      institution between March 2012 and May 2014. In total, 788 patients were included
      in this study. Seventeen patients had postoperative bleeding. The demographics,
      comorbidities, and preoperative medications were similar between the groups. Mean
      postoperative hemoglobin in the bleeding group was significantly lower (94 vs.
      126; P<0.001) with a larger decrease from the baseline value (-43 vs. -12;
      P<0.001). The mean heart rate (91 vs. 81; P<0.001) and its increase from baseline
      (12 vs. -0.01; P<0.001) were significantly different in the bleeding patients.
      Postoperative hemoglobin and heart rate were associated with bleeding but not
      systolic blood pressure or patient characteristics. Further research is needed to
      develop a robust predictive model.

PMID- 29023335
TI  - Radioprotective effect of lycopene on the gastrointestinal tract after high-dose
      radioiodine administration in rat models.
AB  - PURPOSE: The aim of this study was to evaluate the effect of lycopene against
      radioactive iodine (RAI)-related gastrointestinal tract acute damage in a rat
      model as a novel radioprotective agent. MATERIALS AND METHODS: Twenty Wistar
      albino rats were divided into two equal groups: group 1 was administered only RAI
      and group 2 was administered RAI and lycopene. All rats were killed 24 h after
      the last administration of the agents and the gastrointestinal tract organs were
      removed surgically for histopathological examination. RESULT: The presence of
      lamina propria edema in the duodenum (P=0.003) and ileum (P=0.02), ulcer in the
      duodenum (P=0.033), mucosal erosion in the stomach (P=0.001), mucosal
      degeneration in stomach (P=0.02) and colon (P=0.02), necrosis in all tissues (P
      value for stomach=0.005, duodenum=0.001, ileum=0.001, colon=0.001), inflammation
      in those tissues (P value for; stomach=0.003, duodenum=0.02, ileum=0.011,
      colon=0.033), and fibrosis in those tissues (P value for; stomach=0.02,
      duodenum=0.003, ileum=0.003, colon=0.001) were statistically less frequently
      observed in the lycopene group compared with the RAI group. CONCLUSION: As a
      first study assessing the protective effect of lycopene on gastrointestinal tract
      organs in a rat model after RAI, these preliminary basic research findings
      suggest that lycopene appears to exert radioprotective effects against RAI
      induced acute gastrointestinal tract damage.

PMID- 29023334
TI  - Application of Enhanced Recovery After Surgery in Single-incision Laparoscopic
      Distal Gastrectomy.
AB  - BACKGROUND: Recently, enhanced recovery after surgery (ERAS) was widely used in
      the perioperative management of gastric cancer. The study aimed to evaluate the
      safety and effectiveness of ERAS in single-incision laparoscopic distal
      gastrectomy (SIDG). MATERIALS AND METHODS: A total of 90 patients who received
      laparoscopic gastric cancer resection were divided into 3 groups: group A (n=30),
      underwent traditional multiport laparoscopic distal gastrectomy with conventional
      perioperative management; group B (n=30) underwent traditional multiport
      laparoscopic distal gastrectomy with ERAS concept; and group C (n=30), underwent
      SIDG with ERAS concept. Clinical data and gut function were assessed in 3 groups.
      RESULTS: There were no significant differences in terms of postoperative
      complication, number of resected lymph nodes and blood loss among 3 groups.
      However, operation time was longer (P=0.003) and treatment cost was higher
      (P<0.001) in group C than that in group A and B. Group C had faster recovery of
      bowel function (P<0.001), shorter postoperative hospital stay (P=0.002), and less
      postoperative complication (P=0.044) than those in group A. There were no
      significant differences in terms of recovery of bowel function and postoperative
      hospital stay between group C and B (all P>0.05). The white blood cell counts
      were lower than group A and B (all P<0.05) and C-reactive protein in group C were
      lower than group A (P<0.05) and B (P>0.05). CONCLUSIONS: The findings suggest
      that SIDG with ERAS may be a feasible and safe procedure for early gastric cancer
      because it provides a favorable cosmetic result while not compromising
      postoperative complications, number of resected lymph nodes, and blood loss.

PMID- 29023336
TI  - Correlation between functional imaging markers derived from diffusion-weighted
      MRI and 18F-FDG PET/CT in esophageal cancer.
AB  - OBJECTIVE: Both the apparent diffusion coefficient (ADC) acquired by diffusion
      weighted magnetic resonance imaging (DW-MRI) and the standardized uptake value
      (SUV), acquired by F-fluorodeoxyglucose positron emission tomography/computed
      tomography (F-FDG PET/CT), are well-established functional parameters in cancer
      imaging. Currently, it is unclear whether these two markers provide complementary
      prognostic and predictive information in esophageal cancer. The aim of this study
      was to evaluate the correlation between ADC and SUV in patients with esophageal
      cancer. MATERIALS AND METHODS: This prospective study included 76 patients with
      histologically proven esophageal cancer who underwent both DW-MRI and F-FDG
      PET/CT examinations before treatment. The minimum and mean ADC values (ADCmin and
      ADCmean) of the primary tumor were assessed on MRI. Similarly, the glucose
      metabolism was evaluated by the maximum and mean SUV (SUVmax and SUVmean) in the
      same lesions on F-FDG PET/CT images. Spearman's rank correlation coefficients
      were used to assess the correlation between tumor ADC and SUV values. RESULTS:
      The tumor ADC and SUV values as measures of cell density and glucose metabolism,
      respectively, showed negligible nonsignificant correlations (ADCmin vs. SUVmax:
      r=-0.087, P=0.457; ADCmin vs. SUVmean: r=-0.105, P=0.369; ADCmean vs. SUVmax: r=
      0.099, P=0.349; ADCmean vs. SUVmean: r=-0.111, P=0.340). No differences in tumor
      ADC and SUV values were observed between the different histologic tumor types,
      stages, and differentiation grades. CONCLUSION: This study indicates that tumor
      cellularity derived from DW-MRI and tumor metabolism measured by F-FDG PET/CT are
      independent cellular phenomena in newly diagnosed esophageal cancer. Therefore,
      tumor ADC and SUV values may play complementary roles as imaging markers in the
      prediction of survival and evaluation of response to treatment in esophageal
      cancer.

PMID- 29023337
TI  - Recommendations for a Clinical Decision Support System for Work-Related Asthma in
      Primary Care Settings.
AB  - OBJECTIVE: The aim of this study was to describe a recommended clinical decision
      support (CDS) approach for work-related asthma for incorporation in electronic
      health records (EHRs) for primary care health care providers. METHODS: Subject
      matter experts convened by the American Thoracic Society reviewed available
      guidelines and published literature to develop specific recommendations. RESULTS:
      It is important to recognize possible work-related asthma among persons with new
      onset or worsening asthma. The work group recommends incorporating three simple
      questions about temporal relations between asthma symptoms and work in EHR
      systems and identified specific clinical conditions to trigger this intervention.
      Patients with positive responses to the three questions should have the asthma
      diagnosis documented and have further evaluation, education, and possible
      referral. CONCLUSION: An effective CDS system for improving recognition of work
      related asthma may help reduce morbidity and mortality of asthma in adults.

PMID- 29023338
TI  - Using Electronic Health Records and Clinical Decision Support to Provide Return
      to-Work Guidance for Primary Care Practitioners for Patients With Low Back Pain.
AB  - OBJECTIVE: The aim of this study was to describe the process by which a group of
      subject matter experts in the area of return to work developed a resource tool to
      provide clinical decision support (CDS) for primary care clinicians. METHODS: A
      common musculoskeletal disorder, low back pain (LBP), was selected, pertinent
      literature reviewed, and specific recommendations for action in the clinical
      setting developed. RESULTS: Primary care practitioners (PCPs) are routinely
      expected to create work activity prescriptions. The knowledge base for a CDS tool
      that could be embedded in electronic health records has been developed.
      CONCLUSION: Improved clinical support should help prevent and manage work
      limitations associated with LBP not caused by work. The proposed decision support
      should reduce administrative burden and stimulate PCPs to explore the role of
      occupation and its demands on patients.

PMID- 29023339
TI  - Managerial Quality and Risk of Depressive Disorders Among Danish Eldercare
      Workers: A Multilevel Cohort Study.
AB  - OBJECTIVE: To examine whether low managerial quality predicts risk of depressive
      disorders. METHODS: Using multilevel mixed-effects logistic regression analyses
      we examined the prospective association of individual-level and workplace-mean
      managerial quality with onset of depressive disorders among 5244 eldercare
      workers from 274 workplaces during 20 months follow-up. RESULTS: Low managerial
      quality predicted onset of depressive disorders in both the individual-level
      (odds ratio [OR] = 1.85, 95% confidence interval [CI] = 1.25 to 2.76) and the
      workplace-mean analysis (OR = 1.48, 95% CI = 1.06 to 2.07). Low individual-level
      managerial quality predicted onset of depressive disorders when workplace-mean
      managerial quality was high (OR = 3.10, 95% CI = 1.71 to 5.62) but not when it
      was low (OR = 1.07, 95% CI = 0.61 to 1.87). This interaction was statistically
      significant (P = 0.03). CONCLUSIONS: Both low individual-level and low workplace
      mean managerial quality predicted risk of depressive disorders. The association
      was strongest among individuals reporting low managerial quality at workplaces
      with high workplace-mean managerial quality.

PMID- 29023341
TI  - Development and Validation of the Work-Related Well-Being Index: Analysis of the
      Federal Employee Viewpoint Survey (FEVS).
AB  - OBJECTIVE: To describe development and validation of the Work-Related Well-Being
      (WRWB) Index. METHODS: Principal Components Analysis was performed using Federal
      Employee Viewpoint Survey (FEVS) data (N = 392,752) to extract variables
      representing worker well-being constructs. Confirmatory factor analysis was
      performed to verify factor structure. To validate the WRWB index, we used
      multiple regression analysis to examine relationships with burnout associated
      outcomes. RESULTS: PCA identified three positive psychology constructs: "Work
      Positivity", "Co-worker Relationships", and "Work Mastery". An 11 item index
      explaining 63.5% of variance was achieved. The structural equation model provided
      a very good fit to the data. Higher WRWB scores were positively associated with
      all 3 employee experience measures examined in regression models. CONCLUSIONS:
      The new WRWB index shows promise as a valid and widely accessible instrument to
      assess worker well-being.

PMID- 29023342
TI  - Flexible Work: The Impact of a New Policy on Employees' Sedentary Behavior and
      Physical Activity.
AB  - OBJECTIVE: The aim of the study was to assess change in physical activity (PA)
      and sedentary behavior (SB) in office-based employees after the implementation of
      a flexible work policy that allowed working at home. METHODS: A total of 24
      employees (62% female; 40 +/- 10 years) completed an online questionnaire 4 weeks
      pre- and 6 weeks post-implementation of the policy. Changes in PA and SB were
      assessed using Wilcoxon signed rank test. RESULTS: There were no changes in PA
      after the introduction of the flexible work policy (Z = -0.29, P > 0.05). Sitting
      time increased on days the employees worked at home (Z = -2.02, P > 0.05) and on
      days they worked at the office (Z = -4.16, P > 0.001). CONCLUSIONS: A flexible
      work policy may have had a negative impact on sedentary behavior in this
      workplace. Future work is needed to explore the potential impact on workplace
      sitting time.

PMID- 29023340
TI  - Associations Between Disinfection By-Product Exposures and Craniofacial Birth
      Defects.
AB  - OBJECTIVE: The aim of this study was to examine associations between craniofacial
      birth defects (CFDs) and disinfection by-product (DBP) exposures, including the
      sum of four trihalomethanes (THM4) and five haloacetic acids (HAA5) (ie, DBP9).
      METHODS: We calculated first trimester adjusted odds ratios (aORs) for different
      DBPs in a matched case-control study of 366 CFD cases in Massachusetts towns with
      complete 1999 to 2004 THM and HAA data. RESULTS: We detected elevated aORs for
      cleft palate with DBP9 (highest quintile aOR = 3.52; 95% CI: 1.07, 11.60), HAA5,
      trichloroacetic acid (TCAA), and dichloroacetic acid. We detected elevated aORs
      for eye defects with TCAA and chloroform. CONCLUSION: This is the first
      epidemiological study of DBPs to examine eye and ear defects, as well as HAAs and
      CFDs. The associations for cleft palate and eye defects highlight the importance
      of examining specific defects and DBPs beyond THM4.

PMID- 29023344
TI  - Biometric Screening and Future Employer Medical Costs: Is It Worth It to Know?
AB  - OBJECTIVE: To study the relationship between a biometric wellness data and
      future/actual medical costs. METHODS: A relationship between total cholesterol to
      high density lipoprotein ratio, blood pressure, and blood glucose and medical
      costs, based on analysis of claims data, was explored in 1834 employees that had
      both wellness program biometric and claims data in 2016. RESULT: Increased total
      cholesterol to HDL ratio is strongly associated with increased average costs (P <
      0.01). Similarly, an increased glucose level is strongly associated with
      increased average costs (P = 0.001). There was no evidence of a relationship
      between elevated blood pressure and higher costs. CONCLUSIONS: By investing in an
      employer-sponsored biometric screening of full cholesterol and glucose profiles,
      medium-sized employers can identify high-risk employees who are expected to incur
      significantly higher healthcare costs, as compared with low-risk level employees,
      and improve treatment outcomes.

PMID- 29023343
TI  - Pesticide Urinary Metabolites Among Latina Farmworkers and Nonfarmworkers in
      North Carolina.
AB  - OBJECTIVES: This paper compares detections and concentrations of pesticide
      urinary metabolites for Latina farmworkers and nonfarmworkers in North Carolina.
      METHODS: Thirty-one farmworkers and 55 nonfarmworkers provided urine samples in
      2012 and 2013. Urine samples were analyzed for detections and concentrations of
      organophosphate insecticide, bis-dithiocarbamate fungicide, and pyrethroid
      insecticide urinary metabolites. RESULTS: Detections for several organophosphate
      and pyrethroid pesticide urinary metabolites were present for substantial
      proportions of the farmworkers and nonfarmworkers. Concentrations for several of
      these metabolites were high. Farmworkers and nonfarmworkers were similar in
      detections and concentrations for the pesticide urinary metabolites included in
      this analysis. CONCLUSIONS: Participant pesticide exposure increases health risks
      for them and their children. Research needs to document pesticide exposure, its
      health effects, and ways to reduce it. Current information justifies policy
      development to reduce pesticide exposure in all communities.

PMID- 29023345
TI  - Exploring Associations Between Postural Balance and Levels of Urinary
      Organophosphorus Pesticide Metabolites.
AB  - OBJECTIVE: Apply a data-driven approach to explore associations between postural
      balance and pesticide exposure among Latino farmworkers and non-farmworkers.
      METHODS: Lasso-regularized, generalized linear models were used to examine
      associations between postural control measures in four experimental conditions (2
      visual * 2 cognitive difficulty) and dialkylphosphate (DAP) urinary metabolite
      levels. RESULTS: Obtained models generally performed poorly at explaining
      postural control measures. However, when both visual and cognitive conditions
      were altered-the most challenging balance condition-models for some postural
      balance measures contained several DAP metabolites and had relatively better
      fits. CONCLUSIONS: The current results were equivocal regarding associations
      between postural control measures and DAP metabolite concentrations. However,
      farmworker status appears to be an important variable in understanding this
      association. Future work should use a posturally- and cognitively-challenging
      test condition to reveal any potential associations.

PMID- 29023347
TI  - Teicoplanin-Should We Be Doing Routine Therapeutic Drug Monitoring in Children?

PMID- 29023346
TI  - Influenza Vaccination Rate and Reasons for Nonvaccination in Children With
      Cardiac Disease.
AB  - BACKGROUND: Influenza is a major cause of respiratory morbidity worldwide. It
      poses a risk of complications in children with cardiac disease. Influenza vaccine
      is considered the most effective and safe means of preventing the disease. The
      aims of this study were to determine the rate of influenza vaccination in
      children with cardiac disease and to identify the reasons for failure to
      vaccinate in this patient population. METHODS: The study group included 186
      children and their parents who attended the cardiology institute of a tertiary
      pediatric medical center between September and October 2012. Parents were asked
      to complete a questionnaire covering demographics, clinical features, influenza
      vaccination, receipt of advice from medical professionals regarding vaccination
      and personal knowledge about and attitude toward the influenza vaccine. RESULTS:
      Median age of the children was 7.6 years. Thirty-six percent had been vaccinated
      in the previous influenza season. Vaccination was unrelated to the child's age or
      sex or the parents' education. Factors significantly affecting the decision of
      the parents to have their child vaccinated were their knowledge, beliefs and
      conceptions about the vaccine and their receipt of a recommendation to do so from
      the pediatrician or cardiologist (P < 0.001). CONCLUSIONS: The rate of
      vaccination against influenza is low in children with heart disease. Major
      factors encouraging vaccination are proper parental knowledge and the
      recommendation of the primary physician or cardiologist. Medical professionals
      caring for this patient population should be alerted to the need to routinely
      counsel parents on the importance of influenza vaccination.

PMID- 29023348
TI  - Denouement.

PMID- 29023349
TI  - Minimally Invasive Redo Mitral Valve Replacement Using a Robotic-Assisted
      Approach.
AB  - Minimally invasive, robotic-assisted cardiac surgery has been shown to decrease
      transfusion rates, decrease wound infection rates, shorten hospital length of
      stay, and allow for a faster return to full activity compared with traditional
      sternotomy approaches. However, its application has chiefly been limited to
      primary, isolated procedures such as primary mitral valve repair or replacement.
      We describe the first reported use of a robotic surgery platform to perform
      reoperative mitral valve replacement using a minimally invasive, totally
      endoscopic, port-access approach.

PMID- 29023350
TI  - An Artificial Cadaveric Leg Blood Flow System for Endoscopic Vein Harvesting
      Simulation.
AB  - Despite being the most common training model for endoscopic vein harvesting,
      cadaveric legs are limited by their absence of blood flow, resulting in a faded
      vascular appearance. Because the saphenous vein and the surrounding tissue seem
      less distinguishable, dissection of the saphenous vein and bipolar coagulation of
      its branches becomes increasingly inefficient and difficult. An inexpensive
      artificial blood flow system was developed to overcome this limitation. A
      cadaveric leg was thawed to a soft and yielding degree, and the saphenous vein
      was dissected medial and proximal to the medial malleolus. An artificial blood
      solution was prepared by dissolving 4% protein powder, red dye, and a contrast
      agent-for x-ray visualization-in saline. The solution was perfused through the
      saphenous vein and artery. The open ends of the vessels were temporarily clamped
      after the perfusion had been completed. Blood flow within the vessels was
      confirmed via angiography and endoscopic visualization of the leg's vessels. A
      bleeding effect was observed when the saphenous vein was perforated or when a
      vascular branch was transected. Conversely, a tight seal indicated successful
      bipolar coagulation of a branch, providing an objective, quantifiable assessment
      parameter. The artificial blood flow system helps overcome the limitations of the
      cadaveric leg, creating a more realistic and inexpensive model for endoscopic
      vein harvesting simulation training.

PMID- 29023351
TI  - Rapid Deployment Aortic Valves Deliver Superior Hemodynamic Performance In Vitro.
AB  - OBJECTIVE: Clinical studies have demonstrated excellent hemodynamic performance
      of rapid deployment aortic valves; however, few studies have directly compared
      the performance of these valves with conventional bioprosthetic valves. Thus, the
      hemodynamic function of the EDWARDS INTUITY valve (rapid deployment valve) was
      compared with the Edwards Magna Ease valve in vitro (Edwards Lifesciences Corp,
      Irvine, CA USA). METHODS: Elastomeric material was used to create an aortic root
      model that included a left ventricular outflow tract and aortic annulus. The
      model was based on reconstructions from 3-dimensional multislice computed
      tomography images in patients with aortic stenosis; the aortic root was scaled to
      a 21-mm effective annulus diameter. EDWARDS INTUITY valves (21-mm diameter) were
      deployed by stent frame expansion within the aortic root; Edwards Magna Ease
      valves (21-mm diameter) were sutured to the annulus. The left ventricular outflow
      tract area index (left ventricular outflow tract area/baseline area) and
      ellipticity or noncircularity as indexed by Dmax/Dmin were measured under a video
      microscope after valve placement. Hemodynamic data were collected under pulsatile
      flow with saline (70 beats per minute, 5 L/min, 100 mm Hg aortic pressure).
      RESULTS: Compared with the Edwards Magna Ease valve (n = 4), the EDWARDS INTUITY
      valve (n = 4) had a greater effective orifice area (1.56 +/- 0.01 vs 1.85 +/-
      0.06 cm, P < 0.001) and a lower transvalvular pressure gradient (23.4 +/- 0.51 vs
      16.8 +/- 1.3 mm Hg, P < 0.001). Multiple regression analysis showed that 93% of
      the variation in the effective orifice area and transvalvular pressure gradient
      was due to variation in the left ventricular outflow tract area index and
      ellipticity index. CONCLUSIONS: A clinically relevant aortic root model was
      developed to evaluate aortic valve performance. The superior performance of the
      EDWARDS INTUITY valve seemed to be related to both a greater inflow area and a
      more circular left ventricular outflow tract.

PMID- 29023352
TI  - Novel Sternal Protection Device for Cardiac Surgery Via Median Sternotomy
      Incision.
AB  - OBJECTIVE: Sternal bleeding during cardiac surgery is currently controlled using
      bone wax or other chemical substances that may result in adverse effects and
      affect wound healing and recovery. The purpose of this study was to identify a
      safe, cost-effective, and easy-to-use technique to reduce sternal bleeding and
      sternal trauma during cardiac surgery. METHODS: After sternotomy, a sternal
      protection device was placed over each hemisternal section before insertion of
      the retractor and remained in situ until the end of surgery. Sternal bleeding and
      ease of use were assessed and recorded during surgery. Sternal trauma was
      assessed and recorded within 5 minutes of removal of the device, and overall
      satisfaction (Global Impression) and any intraoperative adverse events or device
      malfunction were reported at surgery completion. Patients were followed up 24
      hours and 4 weeks after surgery. RESULTS: Twelve patients completed the study.
      Adverse events reported were not considered related to the device. No sternal
      trauma was identified in any patient. In 9 of 11 patients, sternal bleeding was
      reduced after insertion of the device. The device was generally considered easy
      to use, although some difficulty was encountered when used with the Internal
      Mammary Artery retractor. CONCLUSIONS: Our data suggest that the device is safe
      and able to reduce sternal bleeding during surgery using sternal retractors. We
      recommend further studies in a larger population of patients with a control group
      to evaluate the device's ability to reduce the morbidity associated with sternal
      bleeding and sternal trauma.

PMID- 29023354
TI  - Effects of Hypercapnia on Acute Cellular Rejection after Lung Transplantation in
      Rats.
AB  - BACKGROUND: Hypercapnia alleviates pulmonary ischemia-reperfusion injury,
      regulates T lymphocytes, and inhibits immune reaction. This study aimed to
      evaluate the effect of hypercapnia on acute cellular rejection in a rat lung
      transplantation model. METHODS: Recipient rats in sham-operated (Wistar),
      isograft (Wistar to Wistar), and allograft (Sprague-Dawley to Wistar) groups were
      ventilated with 50% oxygen, whereas rats in the hypercapnia (Sprague-Dawley to
      Wistar) group were administered 50% oxygen and 8% carbon dioxide for 90 min
      during reperfusion (n = 8). Recipients were euthanized 7 days after
      transplantation. RESULTS: The hypercapnia group showed a higher oxygenation index
      (413 +/- 78 vs. 223 +/- 24), lower wet weight-to-dry weight ratio (4.23 +/- 0.54
      vs. 7.04 +/- 0.80), lower rejection scores (2 +/- 1 vs. 4 +/- 1), and lower
      apoptosis index (31 +/- 6 vs. 57 +/- 4) as compared with the allograft group. The
      hypercapnia group showed lower CD8 (17 +/- 4 vs. 31 +/- 3) and CD68 (24 +/- 3 vs.
      43 +/- 2), lower CD8 T cells (12 +/- 2 vs. 35 +/- 6), and higher CD4/CD8 ratio
      (2.2 +/- 0.6 vs. 1.1 +/- 0.4) compared to the allograft group. Tumor necrosis
      factor-alpha (208 +/- 40 vs. 292 +/- 49), interleukin-2 (30.6 +/- 6.7 vs. 52.7 +/
      8.3), and interferon-gamma (28.1 +/- 4.9 vs. 62.7 +/- 10.1) levels in the
      hypercapnia group were lower than those in allograft group. CD4, CD4 T cells, and
      interleukin-10 levels were similar between groups. CONCLUSIONS: Hypercapnia
      ameliorated acute cellular rejection in a rat lung transplantation model.

PMID- 29023355
TI  - Utility of Mobile Communication Devices as a Tool to Improve Adherence to
      Antiretroviral Treatment in HIV-infected Children and Young Adults in Argentina.
AB  - BACKGROUND: Optimal adherence is critical to achieve the benefits of
      antiretroviral treatment (ART). The aim of the study is to evaluate the use of
      mobile devices as a strategy to improve adherence to ART, measured by viral load
      (VL) in HIV+ patients less than 25 years of age. METHODS: A prospective study was
      conducted in a cohort of HIV+ patients less than 25 years of age. HIV+ patients,
      on ART, VL >1000 copies/mL, using mobile devices and suboptimal adherence were
      included. The intervention was based on a mobile generic contact twice a month
      using text message and Facebook during 32 weeks. Extended communications were
      generated by the patient. VL was performed before and after the intervention.
      RESULTS: Twenty-five patients were included. Three were excluded and 22 patients
      were enrolled. Mean age was 17.2 +/- 6.1 years (range: 6-25); 15 (68%) were
      female; mean baseline VL was 25,100 copies/mL (range: 1020-500,000 copies/mL),
      mean log was 4.3 (range: 3-5.7 log). Each participant received a total of 16
      contacts; 84% (296) were answered by the patient and 54% (189) of the contacts
      generated extended communications. After the strategy implementation, 20/22 VL
      results were available: 13/20 (65%) were undetectable, 14/20 (70%) had VL < 1000
      copies/mL and 6/20 (30%) VLs had no changes. CONCLUSIONS: The use of mobile
      devices and social networks is a valid tool to improve ART adherence in HIV+
      pediatric and young adults, evaluated through VL. The strategy is feasible. The
      reminder messages trigger additional communications between patients and health
      provider and better engagement with HIV care. Longer follow-up time is needed.

PMID- 29023356
TI  - Point-of-care Testing in Pediatric Infectious Diseases.

PMID- 29023353
TI  - Staged Repair of a Ruptured Thoracic Aortic Aneurysm Having an Aorto-Parenchymal
      Fistula.
AB  - Ruptured thoracic aortic aneurysms, having aorto-bronchial or pulmonary
      parenchymal fistulations, are life-threatening conditions, and current surgical
      treatment results are not satisfactory. Herein, we describe a 69-year-old man
      with a ruptured thoracic aortic aneurysm and aorto-pulmonary parenchymal
      fistulation that was successfully treated using a staged repair. The first stage
      involved an emergency thoracic endovascular aortic repair for salvage and the
      second stage involved radical pulmonary parenchymal repair with removal of the
      stent graft and aortic reconstruction for long-term survival.

PMID- 29023357
TI  - Pharmacokinetics, Safety and Efficacy of Maraviroc in Treatment-experienced
      Pediatric Patients Infected With CCR5-Tropic HIV-1.
AB  - BACKGROUND: Maraviroc is a CC-chemokine receptor 5 antagonist approved to treat
      adults infected with CC-chemokine receptor 5-tropic (R5) HIV-1. Study A4001031
      was conducted to evaluate the pharmacokinetics, safety and efficacy of maraviroc
      in combination with optimized background therapy in treatment-experienced
      pediatric patients infected with R5 HIV-1 and support registration of maraviroc
      for pediatric use. METHODS: This is an open-label, 2-stage, age-stratified,
      noncomparative multicenter study. One-hundred and three participants were
      enrolled into 4 age/formulation cohorts and dosed twice daily. Initial doses were
      determined by body surface area and optimized background therapy, based on drug
      interactions with maraviroc in adults. Dose adjustment and pharmacokinetic
      reevaluation occurred if the average concentrations (Cavg) at Week 2 were <100
      ng/mL (Stage 1-dose finding). RESULTS: Data from the Week 48 analysis
      demonstrated that 49/50 Stage 1 participants rolling over into Stage 2 (safety
      and efficacy) achieved Cavg >=100 ng/mL. Doses were identified that achieved
      similar concentration ranges to those seen in adults. The majority (90/103)
      received optimized background therapy containing potent cytochrome P450 3A
      inhibitors. Maraviroc was well tolerated and the safety and efficacy were
      comparable to those of adults. All cohorts had a mean decrease from baseline in
      HIV-1 RNA of >1 log10. Increases from baseline in the median CD4+ cell count and
      percentage were seen for all age groups. CONCLUSIONS: The maraviroc dosing
      strategy resulted in participants achieving the target Cavg, with exposure ranges
      similar to those observed in adults on approved doses. The safety and efficacy of
      maraviroc in this pediatric population were comparable to those seen in adults.

PMID- 29023358
TI  - Wrist Acceleration Cut Points for Moderate-to-Vigorous Physical Activity in
      Youth.
AB  - PURPOSE: This study aimed to examine the validity of wrist acceleration cut
      points for classifying moderate (MPA), vigorous (VPA), and moderate-to-vigorous
      (MVPA) physical activity. METHODS: Fifty-seven children (5-12 yr) completed 15
      semistructured activities. Three sets of wrist cut points (>192 mg, >250 mg, and
      >314 mg), previously developed using Euclidian norm minus one (ENMO192+),
      GENEActiv software (GENEA250+), and band-pass filter followed by Euclidian norm
      (BFEN314+), were evaluated against indirect calorimetry. Analyses included
      classification accuracy, equivalence testing, and Bland-Altman procedures.
      RESULTS: All cut points classified MPA, VPA, and MVPA with substantial accuracy
      (ENMO192+: kappa = 0.72 [95% confidence interval = 0.72-0.73], MVPA: area under
      the receiver operating characteristic curve (ROC-AUC) = 0.85 [0.85-0.86];
      GENEA250+: kappa = 0.75 [0.74-0.76], MVPA: ROC-AUC = 0.85 [0.85-0.86]; BFEN314+:
      kappa = 0.73 [0.72-0.74], MVPA: ROC-AUC = 0.86 [0.86-0.87]). BFEN314+
      misclassified 19.7% non-MVPA epochs as MPA, whereas ENMO192+ and GENEA250+
      misclassified 32.6% and 26.5% of MPA epochs as non-MVPA, respectively. Group
      estimates of MPA time were equivalent (P < 0.01) to indirect calorimetry for the
      BFEN314+ MPA cut point (mean bias = -1.5%, limits of agreement [LoA] = -57.5% to
      60.6%), whereas estimates of MVPA time were equivalent (P < 0.01) to indirect
      calorimetry for the ENMO192+ (mean bias = -1.1%, LoA = -53.7% to 55.9%) and
      GENEA250+ (mean bias = 2.2%, LoA = -56.5% to 52.2%) cut points. Individual
      variability (LoA) was large for MPA (min: BFEN314+, -60.6% to 57.5%; max:
      GENEA250+, -42.0% to 104.1%), VPA (min: BFEN314+, -238.9% to 54.6%; max:
      ENMO192+, -244.5% to 127.4%), and MVPA (min: ENMO192+, -53.7% to 55.0%; max:
      BFEN314+, -83.9% to 25.3%). CONCLUSION: Wrist acceleration cut points
      misclassified a considerable proportion of non-MVPA and MVPA. Group-level
      estimates of MVPA were acceptable; however, error for individual-level prediction
      was larger.

PMID- 29023359
TI  - Menstrual Disruption with Exercise Is Not Linked to an Energy Availability
      Threshold.
AB  - INTRODUCTION: Chronic reductions in energy availability (EA) suppress
      reproductive function. A particular calculation of EA quantifies the dietary
      energy remaining after exercise for all physiological functions. Reductions in
      luteinizing hormone pulse frequency have been demonstrated when EA using this
      calculation is <30 kcal.kg.fat-free mass (ffm).d. PURPOSE: We determined whether
      menstrual disturbances (MD) are induced when EA is <30 kcal.kg ffm.d. METHODS:
      Thirty-five sedentary, ovulatory women age 18 to 24 yr (weight, 59.0 +/- 0.8 kg;
      body mass index, 21.8 +/- 0.4 kg.m) completed a diet and exercise intervention
      over three menstrual cycles. Participants were randomized to groups that varied
      in the magnitude of negative energy balance created by the combination of
      exercise and energy restriction. Menstrual disturbances were determined using
      daily urinary estrone-1-glucuronide and pregnanediol glucuronide, midcycle
      luteinizing hormone, and menstrual calendars. In a secondary analysis, we
      calculated EA from energy balance data and tested the association of EA with MD.
      RESULTS: A generalized linear mixed-effects model showed that the likelihood of a
      MD decreased by 9% for each unit increase in EA (odds ratio, 0.91; 95% confidence
      interval, 0.84-0.98; P = 0.010). No specific value of EA emerged as a threshold
      below which MD were induced. When participants were partitioned into EA tertile
      groups (low EA, 23.4-34.1; n = 11; moderate EA, 34.9-40.7; n = 12, and high EA,
      41.2-50.1; n = 12 [kcal.kg ffm.d]), estrone-1-glucuronide (P < 0.001),
      pregnanediol glucuronide (P < 0.001), and luteal phase length (P = 0.031)
      decreased significantly, independent of tertile. CONCLUSIONS: These findings do
      not support that a threshold of EA exists below which MD are induced but do
      suggest that MD increase linearly as EA decreases. Menstrual disturbances can
      likely be prevented by monitoring EA using a simplified assessment of metabolic
      status.

PMID- 29023361
TI  - Procalcitonin and MR-Proadrenomedullin Combination with SOFA and qSOFA Scores for
      Sepsis Diagnosis and Prognosis: A Diagnostic Algorithm.
AB  - PURPOSE: The third Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)
      defined sepsis as an organ dysfunction consequent to infection. A Sequential
      Organ Failure Assessment (SOFA) score at least 2 identifies sepsis. In this
      study, procalcitonin (PCT) and midregional pro-adrenomedullin (MR-proADM) were
      evaluated along with SOFA and quick SOFA (qSOFA) scores in patients with sepsis
      or septic shock. METHODS: A total of 109 septic patients and 50 patients with
      noninfectious disease admitted at the Department of Internal Medicine and General
      Surgery of the University Hospital Campus Bio-Medico of Rome were enrolled. PCT
      and MR-proADM were measured with immunoluminometric assays (Brahms, Hennigsdorf,
      Germany). Data were analyzed with receiver-operating characteristic (ROC) curve
      analysis, likelihood ratios, and Mann-Whitney U test using MedCalc 11.6.1.0
      package. RESULTS: At ROC curve analysis, PCT showed the highest area under the
      curve and positive likelihood ratio values of 27.42 in sepsis and 43.62 in septic
      shock. MR-proADM and SOFA score showed a comparable performance. In septic shock,
      lactate showed the most accurate diagnostic ability. In sepsis, the best
      combination was PCT with MR-proADM with a posttest probability of 0.988. Based
      upon these results, an algorithm for sepsis and septic shock diagnosis has been
      developed. MR-proADM, SOFA, and qSOFA scores significantly discriminated
      survivors from nonsurvivors. CONCLUSIONS: PCT and MR-proADM test combination
      represent a good tool in sepsis diagnosis and prognosis suggesting their
      inclusion in the diagnostic algorithm besides SOFA and qSOFA scores. Furthermore,
      MR-proADM as marker of organ dysfunction, with a turn around time of about 30
      min, has the advantage to be more objective and rapid than SOFA score.

PMID- 29023360
TI  - Honokiol Increases CD4+ T Cell Activation and Decreases TNF but Fails to Improve
      Survival Following Sepsis.
AB  - Honokiol is a biphenolic isolate extracted from the bark of the magnolia tree
      that has been used in traditional Chinese and Japanese medicine, and has more
      recently been investigated for its anti-inflammatory and antibacterial
      properties. Honokiol has previously been demonstrated to improve survival in
      sepsis models that have rapid 100% lethality. The purpose of this study was to
      determine the impact of Honokiol on the host response in a model of sepsis that
      more closely approximates human disease. Male and female C57BL/6 mice underwent
      cecal ligation and puncture to induce polymicrobial intra-abdominal sepsis. Mice
      were then randomized to receive an injection of either Honokiol (120 mg/kg/day)
      or vehicle and were sacrificed after 24 h for functional studies or followed 7
      days for survival. Honokiol treatment after sepsis increased the frequency of CD4
      T cells and increased activation of CD4 T cells as measured by the activation
      marker CD69. Honokiol also increased splenic dendritic cells. Honokiol
      simultaneously decreased frequency and number of CD8 T cells. Honokiol decreased
      systemic tumor necrosis factor without impacting other systemic cytokines.
      Honokiol did not have a detectable effect on kidney function, lung physiology,
      liver function, or intestinal integrity. In contrast to prior studies of Honokiol
      in a lethal model of sepsis, Honokiol did not alter survival at 7 days (70%
      mortality for Honokiol vs. 60% mortality for vehicle). Honokiol is thus effective
      in modulating the host immune response and inflammation following a clinically
      relevant model of sepsis but is not sufficient to alter survival.

PMID- 29023362
TI  - Glycocalyx Shedding is Enhanced by Age and Correlates with Increased Fluid
      Requirement in Patients with Major Burns.
AB  - BACKGROUND: Massive fluid shift after severe burn injury leads to edema and
      intravascular fluid loss that may result in burn-induced compartment syndrome
      (BICS) when corrected by aggressive fluid resuscitation. Factors causing this
      fluid shift remain unclear. Because glycocalyx regulates endothelial
      permeability, we hypothesized that glycocalyx shedding would increase fluid
      requirements in burn patients. This prospective cohort study aimed to identify
      relationships between shedding of the glycocalyx and fluid requirements after
      burn injury. METHODS: Patients aged more than 18 years with burn injury over more
      than 20% total body surface area (TBSA) were enrolled. Patient background factors
      including age, sex, burn size, and inhalation injury were recorded at patient
      enrollment. Serum syndecan-1, known as a biomarker of glycocalyx shedding, was
      serially measured on admission, day 1, days 3 to 5, around 1 and 2 weeks, and 1
      month after the injury to observe postburn injury kinetics of syndecan-1. As
      biomarkers of endothelial damage, soluble thrombomodulin, antithrombin III, and
      plasminogen activator inhibitor-1 were also measured. We determined the
      relationship between syndecan-1 and initial 24-h fluid requirements and between
      syndecan-1 and morbidity/mortality. RESULTS: We enrolled 39 patients (median age,
      55 years; median burn size, 35%TBSA): 16 developed BICS, and 10 patients died.
      Syndecan-1 level on admission was significantly higher than that in healthy
      volunteers and remained so. Syndecan-1 level on admission was associated with
      patient age (rho = 0.50, P = 0.001) but not burn size (rho = 0.08, P = 0.63), and
      antithrombin III level on admission was negatively associated with burn size (rho
      = -0.48, P = 0.002). The syndecan-1 level on admission was significantly
      associated with fluid requirement (mL/kg) (rho = 0.38, P = 0.017). After
      adjustment for age, sex, %TBSA, and inhalation injury, syndecan-1 was an
      independent parameter for the increase in fluid requirement (P = 0.04) and
      development of BICS (P = 0.03) by multivariable regression analysis. These
      findings suggested that glycocalyx shedding increased in an age-dependent manner,
      whereas antithrombin III decreased according to burn size. CONCLUSIONS:
      Glycocalyx shedding occurs soon after burn injury in an age-dependent manner. To
      reduce fluid-related complications such as BICS, new strategies to protect
      glycocalyx in burn patients are needed.

PMID- 29023363
TI  - LPS-Induced Systemic Inflammation Does Not Alter Atherosclerotic Plaque Area or
      Inflammation in APOE3*LEIDEN Mice in the Early Phase Up to 15 Days.
AB  - BACKGROUND AND AIMS: Observational studies show a peak incidence in
      cardiovascular events during and early after clinical conditions associated with
      substantial systemic inflammation, such as pneumonia. The acuteness of this
      increased risk suggests rapid plaque destabilization and associated intraplaque
      inflammation. We evaluated whether lipopolysaccharides (LPS)-evoked acute
      systemic inflammation would induce such detrimental vascular changes in murine
      aortas with manifest atherosclerotic lesions. METHODS AND RESULTS: ApoE3*Leiden
      mice were fed a high cholesterol diet for 20 weeks to establish atherosclerosis.
      Thereafter, mice received a single intraperitoneal injection with LPS to induce
      systemic inflammation, or saline for control. Mice were sacrificed 2 or 15 days
      post-LPS injection (n = 17) or post-saline injection (n = 13). Serum amyloid A, a
      sensitive marker of systemic inflammation, increased 250-fold in LPS-treated
      mice. Aortic root plaques were assessed for total plaque area, plaque severity,
      and inflammatory cell content. No significant differences in total surface area
      of atherosclerotic plaque were found between control and LPS groups sacrificed
      after 2 days (resp. 0.409 +/- 0.228 * 10 MUm vs. 0.285 +/- 0.169 * 10 MUm) (P =
      0.31), and 15 days (resp. 0.950 +/- 0.938 * 10 MUm vs. 0.612 +/- 0.413 * 10 MUm)
      (P = 0.80). Furthermore, plaque type and number of lesions were unaltered and
      intraplaque density of macrophages and lymphocytes were comparable in both the
      groups. CONCLUSIONS: Intraperitoneal LPS injection in ApoE3*Leiden mice triggers
      a profound systemic inflammatory response, but does not increase atherosclerotic
      plaque area or inflammatory cell density. This model of LPS-induced inflammation
      in atherosclerosis-prone mice argues against intraplaque alterations as an
      explanation for acute inflammation-induced cardiovascular event risk.

PMID- 29023364
TI  - Feature Weight Driven Interactive Mutual Information Modeling for Heterogeneous
      Bio-Signal Fusion to Estimate Mental Workload.
AB  - Many people suffer from high mental workload which may threaten human health and
      cause serious accidents. Mental workload estimation is especially important for
      particular people such as pilots, soldiers, crew and surgeons to guarantee the
      safety and security. Different physiological signals have been used to estimate
      mental workload based on the n-back task which is capable of inducing different
      mental workload levels. This paper explores a feature weight driven signal fusion
      method and proposes interactive mutual information modeling (IMIM) to increase
      the mental workload classification accuracy. We used EEG and ECG signals to
      validate the effectiveness of the proposed method for heterogeneous bio-signal
      fusion. The experiment of mental workload estimation consisted of signal
      recording, artifact removal, feature extraction, feature weight calculation, and
      classification. Ten subjects were invited to take part in easy, medium and hard
      tasks for the collection of EEG and ECG signals in different mental workload
      levels. Therefore, heterogeneous physiological signals of different mental
      workload states were available for classification. Experiments reveal that ECG
      can be utilized as a supplement of EEG to optimize the fusion model and improve
      mental workload estimation. Classification results show that the proposed bio
      signal fusion method IMIM can increase the classification accuracy in both
      feature level and classifier level fusion. This study indicates that multi-modal
      signal fusion is promising to identify the mental workload levels and the fusion
      strategy has potential application of mental workload estimation in cognitive
      activities during daily life.

PMID- 29023365
TI  - Soft Smart Garments for Lower Limb Joint Position Analysis.
AB  - Revealing human movement requires lightweight, flexible systems capable of
      detecting mechanical parameters (like strain and pressure) while being worn
      comfortably by the user, and not interfering with his/her activity. In this work
      we address such multifaceted challenge with the development of smart garments for
      lower limb motion detection, like a textile kneepad and anklet in which soft
      sensors and readout electronics are embedded for retrieving movement of the
      specific joint. Stretchable capacitive sensors with a three-electrode
      configuration are built combining conductive textiles and elastomeric layers, and
      distributed around knee and ankle. Results show an excellent behavior in the ~30%
      strain range, hence the correlation between sensors' responses and the optically
      tracked Euler angles is allowed for basic lower limb movements. Bending during
      knee flexion/extension is detected, and it is discriminated from any external
      contact by implementing in real time a low computational algorithm. The smart
      anklet is designed to address joint motion detection in and off the sagittal
      plane. Ankle dorsi/plantar flexion, adduction/abduction, and rotation are
      retrieved. Both knee and ankle smart garments show a high accuracy in movement
      detection, with a RMSE less than 4 degrees  in the worst case.

PMID- 29023366
TI  - Personalized Nanomedicine: A Revolution at the Nanoscale.
AB  - Nanomedicine is an interdisciplinary research field that results from the
      application of nanotechnology to medicine and has the potential to significantly
      improve some current treatments. Specifically, in the field of personalized
      medicine, it is expected to have a great impact in the near future due to its
      multiple advantages, namely its versatility to adapt a drug to a cohort of
      patients. In the present review, the properties and requirements of
      pharmaceutical dosage forms at the nanoscale, so-called nanomedicines, are been
      highlighted. An overview of the main current nanomedicines in pre-clinical and
      clinical development is presented, detailing the challenges to the
      personalization of these therapies. Next, the process of development of novel
      nanomedicines is described, from their design in research labs to their arrival
      on the market, including considerations for the design of nanomedicines adapted
      to the requirements of the market to achieve safe, effective, and quality
      products. Finally, attention is given to the point of view of the pharmaceutical
      industry, including regulation issues applied to the specific case of
      personalized medicine. The authors expect this review to be a useful overview of
      the current state of the art of nanomedicine research and industrial production,
      and the future opportunities of personalized medicine in the upcoming years. The
      authors encourage the development and marketing of novel personalized
      nanomedicines.

PMID- 29023367
TI  - Effect of Cadmium and Copper Exposure on Growth, Secondary Metabolites and
      Antioxidant Activity in the Medicinal Plant Sambung Nyawa (Gynura procumbens
      (Lour.) Merr).
AB  - A randomized complete block (RCBD) study was designed to investigate the effects
      of cadmium (Cd) and copper (Cu) on the growth, bioaccumulation of the two heavy
      metals, metabolite content and antibacterial activities in Gyanura procumbens
      (Lour.) Merr. Nine treatments including (1) control (no Cd and Cu); (2) Cd 2 =
      cadmium 2 mg/L; (3) Cd 4 = cadmium 4 mg/L; (4) Cu 70 = copper 70 mg/L; (5) Cu 140
      = copper 140 mg/L); (6) Cd 2 + Cu 70 = cadmium 2 mg/L + copper 70 mg/L); (7) Cd 2
      + Cu 140 = cadmium 2 mg/L + copper 70 mg/L); (8) Cd 4 + Cu 70 = cadmium 4 mg/L+
      copper 70 mg/L and (9) Cd 4 + Cu 140 = cadmium 4 mg/L + copper 140 mg/L) were
      evaluated in this experiment. It was found that the growth parameters (plant dry
      weight, total leaf area and basal diameter) were reduced with the exposure to
      increased concentrations of Cd and Cu and further decreased under interaction
      between Cd and Cu. Production of total phenolics, flavonoids and saponin was
      observed to be reduced under combined Cd and Cu treatment. The reduction in the
      production of plant secondary metabolites might be due to lower phenyl alanine
      lyase (PAL) activity under these conditions. Due to that, the 1,1-diphenyl-2
      picrylhydrazyl (DPPH), ferric reducing antioxidant potential (FRAP) and
      antibacterial activities was also found to be reduced by the combined treatments.
      The current experiments show that the medicinal properties of G. procumbens are
      reduced by cadmium and copper contamination. The accumulation of heavy metal also
      was found to be higher than the safety level recommended by the WHO in the single
      and combined treatments of Cd and Cu. These results indicate that exposure of G.
      procumbens to Cd and Cu contaminated soil may potentially harm consumers due to
      bioaccumulation of metals and reduced efficacy of the herbal product.

PMID- 29023369
TI  - TiO2 Nanowire Networks Prepared by Titanium Corrosion and Their Application to
      Bendable Dye-Sensitized Solar Cells.
AB  - TiO2 nanowire networks were prepared, using the corrosion of Ti foils in alkaline
      (potassium hydroxide, KOH) solution at different temperatures, and then a further
      ion-exchange process. The prepared nanostructures were characterized by field
      emission scanning electron microscopy, Raman spectroscopy, and X-ray
      photoelectron spectroscopy. The wet corroded foils were utilized as the
      photoanodes of bendable dye-sensitized solar cells (DSSCs), which exhibited a
      power conversion efficiency of 1.11% under back illumination.

PMID- 29023368
TI  - The Evolutionary History and Spatiotemporal Dynamics of the NC Lineage of Citrus
      Tristeza Virus.
AB  - Citrus tristeza virus (CTV) is a major pathogen affecting citrus trees worldwide.
      However, few studies have focused on CTV's evolutionary history and geographic
      behavior. CTV is locally dispersed by an aphid vector and long distance
      dispersion due to transportation of contaminated material. With the aim to delve
      deeper into the CTV-NC (New Clade) genotype evolution, we estimated an evolution
      rate of 1.19 * 10-3 subs/site/year and the most common recent ancestor in 1977.
      Furthermore, the place of origin of the genotype was in the United States, and a
      great expansion of the population was observed in Uruguay. This expansion phase
      could be a consequence of the increment in the number of naive citrus trees in
      Uruguayan orchards encompassing citrus industry growth in the past years.

PMID- 29023370
TI  - Self-Evaluation of PANDA-FBG Based Sensing System for Dynamic Distributed Strain
      and Temperature Measurement.
AB  - A novel method is introduced in this work for effectively evaluating the
      performance of the PANDA type polarization-maintaining fiber Bragg grating (PANDA
      FBG) distributed dynamic strain and temperature sensing system. Conventionally,
      the errors during the measurement are unknown or evaluated by using other sensors
      such as strain gauge and thermocouples. This will make the sensing system
      complicated and decrease the efficiency since more than one kind of sensor is
      applied for the same measurand. In this study, we used the approximately constant
      ratio of primary errors in strain and temperature measurement and realized the
      self-evaluation of the sensing system, which can significantly enhance the
      applicability, as well as the reliability in strategy making.

PMID- 29023372
TI  - PARP Inhibition by Flavonoids Induced Selective Cell Killing to BRCA2-Deficient
      Cells.
AB  - High consumption of dietary flavonoids might contribute to a reduction of cancer
      risks. Quercetin and its glycosides have PARP inhibitory effects and can induce
      selective cytotoxicity in BRCA2-deficient cells by synthetic lethality. We
      hypothesized that common flavonoids in diet naringenin, hesperetin and their
      glycosides have a similar structure to quercetin, which might have comparable
      PARP inhibitory effects, and can induce selective cytotoxicity in BRCA2-deficient
      cells. We utilized Chinese hamster V79 wild type, V-C8 BRCA2-deficient and its
      gene-complemented cells. In vitro analysis revealed that both naringenin and
      hesperetin present a PARP inhibitory effect. This inhibitory effect is less
      specific than for quercetin. Hesperetin was more cytotoxic to V79 cells than
      quercetin and naringenin based on colony formation assay. Quercetin and
      naringenin killed V-C8 cells with lower concentrations, and presented selective
      cytotoxicity to BRCA2-deficient cells. However, the cytotoxicity of hesperetin
      was similar among all three cell lines. Glycosyl flavonoids, isoquercetin and
      rutin as well as naringin showed selective cytotoxicity to BRCA2-deficient cells;
      hesperidin did not. These results suggest that flavonoids with the PARP
      inhibitory effect can cause synthetic lethality to BRCA2-deficient cells when
      other pathways are not the primary cause of death.

PMID- 29023373
TI  - Evaluation of the Ability of Nanostructured PEI-Coated Iron Oxide Nanoparticles
      to Incorporate Cisplatin during Synthesis.
AB  - Nanoparticles (NPs) have a high potential for biological applications as they can
      be used as carriers for the controlled release of bioactive factors. Here we
      focused on poly(ethylenimine) (PEI)-coated iron oxide hybrid NPs obtained by
      hydrothermal synthesis in high pressure conditions and evaluated their behavior
      in culture medium in the presence or absence of cells, as well as their ability
      to incorporate antitumor drug cisplatin. Our results showed that the hydrothermal
      conditions used for Fe-PEI NPs synthesis allowed the incorporation of cisplatin,
      which even increased its anti-tumor effects. Furthermore, the commonly occurring
      phenomenon of NPs aggregation in culture medium was exploited for further
      entrapment of other active molecules, such as the fluorescent dye DiI and
      valinomycin. The molecules bound to NPs during synthesis or during aggregation
      process were delivered inside various cells after in vitro and in vivo direct
      contact between cells and NPs and their biological activity was preserved, thus
      supporting the therapeutic value of Fe-PEI NPs as drug delivery tools.

PMID- 29023371
TI  - Expression Profiles of Ligands for Activating Natural Killer Cell Receptors on
      HIV Infected and Uninfected CD4+ T Cells.
AB  - Natural Killer (NK) cell responses to HIV-infected CD4 T cells (iCD4) depend on
      the integration of signals received through inhibitory (iNKR) and activating NK
      receptors (aNKR). iCD4 activate NK cells to inhibit HIV replication. HIV
      infection-dependent changes in the human leukocyte antigen (HLA) ligands for iNKR
      on iCD4 are well documented. By contrast, less is known regarding the HIV
      infection related changes in ligands for aNKR on iCD4. We examined the aNKR
      ligand profiles HIV p24+ HIV iCD4s that maintained cell surface CD4 (iCD4+), did
      not maintain CD4 (iCD4-) and uninfected CD4 (unCD4) T cells for expression of
      unique long (UL)-16 binding proteins-1 (ULBP-1), ULBP-2/5/6, ULBP-3, major
      histocompatibility complex (MHC) class 1-related (MIC)-A, MIC-B, CD48, CD80,
      CD86, CD112, CD155, Intercellular adhesion molecule (ICAM)-1, ICAM-2, HLA-E, HLA
      F, HLA-A2, HLA-C, and the ligands to NKp30, NKp44, NKp46, and killer
      immunoglobulin-like receptor 3DS1 (KIR3DS1) by flow cytometry on CD4 T cells from
      17 HIV-1 seronegative donors activated and infected with HIV. iCD4+ cells had
      higher expression of aNKR ligands than did unCD4. However, the expression of aNKR
      ligands on iCD4 where CD4 was downregulated (iCD4-) was similar to (ULBP-1, ULBP
      2/5/6, ULBP-3, MIC-A, CD48, CD80, CD86 and CD155) or significantly lower than
      (MIC-B, CD112 and ICAM-2) what was observed on unCD4. Thus, HIV infection can be
      associated with increased expression of aNKR ligands or either baseline or lower
      than baseline levels of aNKR ligands, concomitantly with the HIV-mediated
      downregulation of cell surface CD4 on infected cells.

PMID- 29023374
TI  - Periodic TiO2 Nanostructures with Improved Aspect and Line/Space Ratio Realized
      by Colloidal Photolithography Technique.
AB  - This paper presents substantial improvements of the colloidal photolithography
      technique (also called microsphere lithography) with the goal of better
      controlling the geometry of the fabricated nano-scale structures-in this case,
      hexagonally arranged nanopillars-printed in a layer of directly photopatternable
      sol-gel TiO2. Firstly, to increase the achievable structure height the
      photosensitive layer underneath the microspheres is deposited on a reflective
      layer instead of the usual transparent substrate. Secondly, an increased width of
      the pillars is achieved by tilting the incident wave and using multiple exposures
      or substrate rotation, additionally allowing to better control the shape of the
      pillar's cross section. The theoretical analysis is carried out by rigorous
      modelling of the photonics nanojet underneath the microspheres and by optimizing
      the experimental conditions. Aspect ratios (structure height/lateral structure
      size) greater than 2 are predicted and demonstrated experimentally for structure
      dimensions in the sub micrometer range, as well as line/space ratios (lateral
      pillar size/distance between pillars) greater than 1. These nanostructures could
      lead for example to materials exhibiting efficient light trapping in the visible
      and near-infrared range, as well as improved hydrophobic or photocatalytic
      properties for numerous applications in environmental and photovoltaic systems.

PMID- 29023375
TI  - Workflow for Criticality Assessment Applied in Biopharmaceutical Process
      Validation Stage 1.
AB  - Identification of critical process parameters that impact product quality is a
      central task during regulatory requested process validation. Commonly, this is
      done via design of experiments and identification of parameters significantly
      impacting product quality (rejection of the null hypothesis that the effect
      equals 0). However, parameters which show a large uncertainty and might result in
      an undesirable product quality limit critical to the product, may be missed. This
      might occur during the evaluation of experiments since residual/un-modelled
      variance in the experiments is larger than expected a priori. Estimation of such
      a risk is the task of the presented novel retrospective power analysis
      permutation test. This is evaluated using a data set for two unit operations
      established during characterization of a biopharmaceutical process in industry.
      The results show that, for one unit operation, the observed variance in the
      experiments is much larger than expected a priori, resulting in low power levels
      for all non-significant parameters. Moreover, we present a workflow of how to
      mitigate the risk associated with overlooked parameter effects. This enables a
      statistically sound identification of critical process parameters. The developed
      workflow will substantially support industry in delivering constant product
      quality, reduce process variance and increase patient safety.

PMID- 29023376
TI  - Altered Protein Expression of Cardiac CYP2J and Hepatic CYP2C, CYP4A, and CYP4F
      in a Mouse Model of Type II Diabetes-A Link in the Onset and Development of
      Cardiovascular Disease?
AB  - Arachidonic acid can be metabolized by cytochrome P450 (CYP450) enzymes in a
      tissue- and cell-specific manner to generate vasoactive products such as
      epoxyeicosatrienoic acids (EETs-cardioprotective) and hydroxyeicosatetraenoic
      acids (HETEs-cardiotoxic). Type II diabetes is a well-recognized risk factor for
      developing cardiovascular disease. A mouse model of Type II diabetes (C57BLKS/J
      db/db) was used. After sacrifice, livers and hearts were collected, washed, and
      snap frozen. Total proteins were extracted. Western blots were performed to
      assess cardiac CYP2J and hepatic CYP2C, CYP4A, and CYP4F protein expression,
      respectively. Significant decreases in relative protein expression of cardiac
      CYP2J and hepatic CYP2C were observed in Type II diabetes animals compared to
      controls (CYP2J: 0.80 +/- 0.03 vs. 1.05 +/- 0.06, n = 20, p < 0.001); (CYP2C:
      1.56 +/- 0.17 vs. 2.21 +/- 0.19, n = 19, p < 0.01). In contrast, significant
      increases in relative protein expression of both hepatic CYP4A and CYP4F were
      noted in Type II diabetes mice compared to controls (CYP4A: 1.06 +/- 0.09 vs.
      0.18 +/- 0.01, n = 19, p < 0.001); (CYP4F: 2.53 +/- 0.22 vs. 1.10 +/- 0.07, n =
      19, p < 0.001). These alterations induced by Type II diabetes in the endogenous
      pathway (CYP450) of arachidonic acid metabolism may increase the risk for
      cardiovascular disease by disrupting the fine equilibrium between
      cardioprotective (CYP2J/CYP2C-generated) and cardiotoxic (CYP4A/CYP4F-generated)
      metabolites of arachidonic acid.

PMID- 29023377
TI  - Response of Intestinal Bacterial Flora to the Long-term Feeding of Aflatoxin B1
      (AFB1) in Mice.
AB  - In order to investigate the influence of aflatoxin B1 (AFB1) on intestinal
      bacterial flora, 24 Kunming mice (KM mice) were randomly placed into four groups,
      which were labeled as control, low-dose, medium-dose, and high-dose groups. They
      were fed intragastrically with 0.4 mL of 0 mg/L, 2.5 mg/L, 4 mg/L, or 10 mg/L of
      AFB1 solutions, twice a day for 2 months. The hypervariable region V3 + V4 on 16S
      rDNA of intestinal bacterial flora was sequenced by the use of a high-flux
      sequencing system on a Miseq Illumina platform; then, the obtained sequences were
      analyzed. The results showed that, when compared with the control group, both
      genera and phyla of intestinal bacteria in the three treatment groups decreased.
      About one third of the total genera and one half of the total phyla remained in
      the high-dose group. The dominant flora were Lactobacillus and Bacteroides in all
      groups. There were significant differences in the relative abundance of
      intestinal bacterial flora among groups. Most bacteria decreased as a whole from
      the control to the high-dose groups, but several beneficial and pathogenic
      bacterial species increased significantly with increasing dose of AFB1. Thus, the
      conclusion was that intragastric feeding with 2.5~10 mg/mL AFB1 for 2 months
      could decrease the majority of intestinal bacterial flora and induce the
      proliferation of some intestinal bacteria flora.

PMID- 29023378
TI  - The Effects of Data Collection Method and Monitoring of Workers' Behavior on the
      Generation of Demolition Waste.
AB  - The roles of both the data collection method (including proper classification)
      and the behavior of workers on the generation of demolition waste (DW) are
      important. By analyzing the effect of the data collection method used to estimate
      DW, and by investigating how workers' behavior can affect the total amount of DW
      generated during an actual demolition process, it was possible to identify
      strategies that could improve the prediction of DW. Therefore, this study
      surveyed demolition waste generation rates (DWGRs) for different types of
      building by conducting on-site surveys immediately before demolition in order to
      collect adequate and reliable data. In addition, the effects of DW management
      strategies and of monitoring the behavior of workers on the actual generation of
      DW were analyzed. The results showed that when monitoring was implemented, the
      estimates of DW obtained from the DWGRs that were surveyed immediately before
      demolition and the actual quantities of DW reported by the demolition contractors
      had an error rate of 0.63% when the results were compared. Therefore, this study
      has shown that the proper data collection method (i.e., data were collected
      immediately before demolition) applied in this paper and monitoring on the
      demolition site have a significant impact on waste generation.

PMID- 29023379
TI  - Effect of Early Pelvic Binder Use in the Emergency Management of Suspected Pelvic
      Trauma: A Retrospective Cohort Study.
AB  - BACKGROUND: We aimed to evaluate the effect of early pelvic binder use in the
      emergency management of suspected pelvic trauma, compared with the conventional
      stepwise approach. METHODS: We enrolled trauma patients with initial
      stabilization using a pelvic binder when suspecting pelvic injury. The inclusion
      criteria were traumatic injury requiring a trauma team and at least one of the
      following: a loss of consciousness or a Glasgow coma score (GCS) of <13; systolic
      blood pressure of <90 mmHg; falling from >=6 m; injury to multiple vital organs;
      and suspected pelvic injury. Various parameters, including gender, age, mechanism
      of injury, GCS, mortality, hospital stay, initial vital signs, revised trauma
      score, injury severity score, and outcome, were assessed and compared with
      historical controls. RESULTS: A total of 204 patients with high-energy multiple
      trauma from a single level I trauma center in North Taiwan were enrolled in the
      study from August 2013 to July 2014. The two group baseline patient
      characteristics were all collected and compared. The trauma patients with
      suspected pelvic fractures initially stabilized with a pelvic binder had shorter
      hospital and intensive care unit (ICU) stays. The study group achieved
      statistically significantly improved survival and lower mean blood transfusion
      volume and mortality rate, although they were more severe in the trauma score.
      CONCLUSIONS: We recommend prompt pelvic binder use for suspected pelvic injury
      before definitive imaging is available, as a cervical spine collar is used to
      protect the cervical spine from further injury prior to definitive identification
      and characterization of an injury.

PMID- 29023381
TI  - Design of a Low-Cost Air Levitation System for Teaching Control Engineering.
AB  - Air levitation is the process by which an object is lifted without mechanical
      support in a stable position, by providing an upward force that counteracts the
      gravitational force exerted on the object. This work presents a low-cost lab
      implementation of an air levitation system, based on open solutions. The rapid
      dynamics makes it especially suitable for a control remote lab. Due to the
      system's nature, the design can be optimized and, with some precision trade-off,
      kept affordable both in cost and construction effort. It was designed to be
      easily adopted to be used as both a remote lab and as a hands-on lab.

PMID- 29023382
TI  - Quantification of Representative Ciguatoxins in the Pacific Using Quantitative
      Nuclear Magnetic Resonance Spectroscopy.
AB  - The absolute quantification of five toxins involved in ciguatera fish poisoning
      (CFP) in the Pacific was carried out by quantitative 1H-NMR. The targeted toxins
      were ciguatoxin-1B (CTX1B), 52-epi-54-deoxyciguatoxin-1B (epideoxyCTX1B),
      ciguatoxin-3C (CTX3C), 51-hydroxyciguatoxin-3C (51OHCTX3C), and ciguatoxin-4A
      (CTX4A). We first calibrated the residual protons of pyridine-d5 using certified
      reference material, 1,4-BTMSB-d4, prepared the toxin solutions with the
      calibrated pyridin-d5, measured the 1H-NMR spectra, and quantified the toxin
      using the calibrated residual protons as the internal standard. The absolute
      quantification was carried out by comparing the signal intensities between the
      selected protons of the target toxin and the residual protons of the calibrated
      pyridine-d5. The proton signals residing on the ciguatoxins (CTXs) to be used for
      quantification were carefully selected for those that were well separated from
      adjacent signals including impurities and that exhibited an effective intensity.
      To quantify CTX1B and its congeners, the olefin protons in the side chain were
      judged appropriate for use. The quantification was achievable with nano-molar
      solutions. The probable errors for uncertainty, calculated on respective toxins,
      ranged between 3% and 16%. The contamination of the precious toxins with
      nonvolatile internal standards was thus avoided. After the evaporation of
      pyridine-d5, the calibrated CTXs were ready for use as the reference standard in
      the quantitative analysis of ciguatoxins by LC/MS.

PMID- 29023383
TI  - AAL Platform with a "De Facto" Standard Communication Interface (TICO): Training
      in Home Control in Special Education.
AB  - Framed within a long-term cooperation between university and special education
      teachers, training in alternative communication skills and home control was
      realized using the "TICO" interface, a communication panel editor extensively
      used in special education schools. From a technological view we follow AAL
      technology trends by integrating a successful interface in a heterogeneous
      services AAL platform, focusing on a functional view. Educationally, a very
      flexible interface in line with communication training allows dynamic adjustment
      of complexity, enhanced by an accessible mindset and virtual elements
      significance already in use, offers specific interaction feedback, adapts to the
      evolving needs and capacities and improves the personal autonomy and self
      confidence of children at school and home. TICO-home-control was installed during
      the last school year in the library of a special education school to study
      adaptations and training strategies to enhance the autonomy opportunities of its
      pupils. The methodology involved a case study and structured and semi-structured
      observations. Five children, considered unable to use commercial home control
      systems were trained obtaining good results in enabling them to use an open home
      control system. Moreover this AAL platform has proved efficient in training
      children in previous cognitive steps like virtual representation and cause-effect
      interaction.

PMID- 29023380
TI  - The Gut Microbiome Feelings of the Brain: A Perspective for Non-Microbiologists.
AB  - Objectives: To comprehensively review the scientific knowledge on the gut-brain
      axis. Methods: Various publications on the gut-brain axis, until 31 July 2017,
      were screened using the Medline, Google, and Cochrane Library databases. The
      search was performed using the following keywords: "gut-brain axis", "gut
      microbiota-brain axis", "nutrition microbiome/microbiota", "enteric nervous
      system", "enteric glial cells/network", "gut-brain pathways", "microbiome immune
      system", "microbiome neuroendocrine system" and "intestinal/gut/enteric
      neuropeptides". Relevant articles were selected and reviewed. Results: Tremendous
      progress has been made in exploring the interactions between nutrients, the
      microbiome, and the intestinal, epithelium-enteric nervous, endocrine and immune
      systems and the brain. The basis of the gut-brain axis comprises of an array of
      multichannel sensing and trafficking pathways that are suggested to convey the
      enteric signals to the brain. These are mediated by neuroanatomy (represented by
      the vagal and spinal afferent neurons), the neuroendocrine-hypothalamic-pituitary
      adrenal (HPA) axis (represented by the gut hormones), immune routes (represented
      by multiple cytokines), microbially-derived neurotransmitters, and finally the
      gate keepers of the intestinal and brain barriers. Their mutual and harmonious
      but intricate interaction is essential for human life and brain performance.
      However, a failure in the interaction leads to a number of inflammatory-,
      autoimmune-, neurodegenerative-, metabolic-, mood-, behavioral-, cognitive-,
      autism-spectrum-, stress- and pain-related disorders. The limited availability of
      information on the mechanisms, pathways and cause-and-effect relationships
      hinders us from translating and implementing the knowledge from the bench to the
      clinic. Implications: Further understanding of this intricate field might
      potentially shed light on novel preventive and therapeutic strategies to combat
      these disorders. Nutritional approaches, microbiome manipulations, enteric and
      brain barrier reinforcement and sensing and trafficking modulation might improve
      physical and mental health outcomes.

PMID- 29023385
TI  - Implementation of High Time Delay Accuracy of Ultrasonic Phased Array Based on
      Interpolation CIC Filter.
AB  - In order to improve the accuracy of ultrasonic phased array focusing time delay,
      analyzing the original interpolation Cascade-Integrator-Comb (CIC) filter, an 8*
      interpolation CIC filter parallel algorithm was proposed, so that interpolation
      and multichannel decomposition can simultaneously process. Moreover, we
      summarized the general formula of arbitrary multiple interpolation CIC filter
      parallel algorithm and established an ultrasonic phased array focusing time delay
      system based on 8* interpolation CIC filter parallel algorithm. Improving the
      algorithmic structure, 12.5% of addition and 29.2% of multiplication was reduced,
      meanwhile the speed of computation is still very fast. Considering the existing
      problems of the CIC filter, we compensated the CIC filter; the compensated CIC
      filter's pass band is flatter, the transition band becomes steep, and the stop
      band attenuation increases. Finally, we verified the feasibility of this
      algorithm on Field Programming Gate Array (FPGA). In the case of system clock is
      125 MHz, after 8* interpolation filtering and decomposition, time delay accuracy
      of the defect echo becomes 1 ns. Simulation and experimental results both show
      that the algorithm we proposed has strong feasibility. Because of the fast
      calculation, small computational amount and high resolution, this algorithm is
      especially suitable for applications with high time delay accuracy and fast
      detection.

PMID- 29023384
TI  - Nano-Formulation of Ethambutol with Multifunctional Graphene Oxide and Magnetic
      Nanoparticles Retains Its Anti-Tubercular Activity with Prospects of Improving
      Chemotherapeutic Efficacy.
AB  - Tuberculosis (TB) is a dreadful bacterial disease, infecting millions of human
      and cattle every year worldwide. More than 50 years after its discovery,
      ethambutol continues to be an effective part of the World Health Organization's
      recommended frontline chemotherapy against TB. However, the lengthy treatment
      regimens consisting of a cocktail of antibiotics affect patient compliance. There
      is an urgent need to improve the current therapy so as to reduce treatment
      duration and dosing frequency. In this study, we have designed a novel anti-TB
      multifunctional formulation by fabricating graphene oxide with iron oxide
      magnetite nanoparticles serving as a nano-carrier on to which ethambutol was
      successfully loaded. The designed nanoformulation was characterised using various
      analytical techniques. The release of ethambutol from anti-TB multifunctional
      nanoparticles formulation was found to be sustained over a significantly longer
      period of time in phosphate buffer saline solution at two physiological pH (7.4
      and 4.8). Furthermore, the nano-formulation showed potent anti-tubercular
      activity while remaining non-toxic to the eukaryotic cells tested. The results of
      this in vitro evaluation of the newly designed nano-formulation endorse its
      further development in vivo.

PMID- 29023386
TI  - The Immunogenicity of Branded and Biosimilar Infliximab in Rheumatoid Arthritis
      According to Th9-Related Responses.
AB  - : Our objective was to evaluate the immunogenicity of branded and biosimilar
      infliximab by detecting changes in T-helper-9 (Th9) percentages induced by an in
      vitro stimulation test. METHODS: Peripheral blood mononuclear cells collected
      from 55 consecutive rheumatoid arthritis (RA) outpatients (15 drug free, 20
      successfully treated with branded infliximab, 20 branded infliximab inadequate
      responders) and 10 healthy controls were cultured, with or without 50 MUg/mL of
      infliximab originator (Remicade(r)) or 50 MUg/mL of infliximab biosimilar
      (Remsima(r)) for 18 h. Th9 lymphocytes were identified by means of flow cytometry
      as PU.1 and IRF4-expressing, IL-9-secreting CD4+ T cells. Furthermore, the
      markers CCR7 and CD45RA were used to distinguish naive from memory IL-9 producer
      cells. RESULTS: Under unstimulated conditions, the drug-free RA patients had the
      highest percentages of Th9 lymphocytes. Following stimulation with branded
      infliximab, the percentages of PU.1 and IRF4-expressing Th9 cells, CCR7+, CD45RA-
      (central memory) and CCR7-, CD45RA- (effector memory) cells significantly
      increased in the group of inadequate responders, but no significant variation was
      observed after exposure to the biosimilar of infliximab. CONCLUSIONS: Th9 cells
      seem to be involved in the immune response to the epitopes of branded, but not
      biosimilar, infliximab, and this may depend on the recall and stimulation of both
      central and effector memory cells.

PMID- 29023387
TI  - Combination of beta-glucan and Morus alba L. Leaf Extract Promotes Metabolic
      Benefits in Mice Fed a High-Fat Diet.
AB  - beta-glucan (BG) and mulberry have received increasing attention for their
      benefits as natural sources of metabolic health. In the current study, we
      investigated the synergetic beneficial effects of BG and mulberry leaf extract
      (MLE) in mice fed a high-fat diet (HFD). Male C57BL6 mice were fed a HFD for
      twelve weeks to induce significant obesity and insulin resistance. BG and MLE
      were administrated orally throughout the feeding period. The administration of BG
      resulted in a significant reduction in body weight gain, perirenal fat mass,
      fasting insulin, serum lipids, serum inflammation markers, and fatty liver,
      showing systemic health improvement. Likewise, the administration of MLE showed
      benefits similar to BG, with the exception of body weight gain. In addition to
      the systemic benefits, the combination of BG and MLE resulted in a synergetic
      improvement in insulin sensitivity. Meanwhile, only the combination of BG and MLE
      significantly enhanced liver GST (Glutathione S-Transferase) activity and CuZn
      SOD (Superoxide dismutase (Cu-Zn)) activity, resulting in a significant reduction
      in GSH/GSSG (Glutathione disulfide) and reactive oxygen species (ROS) levels in
      the liver. These results further confirm the beneficial effects of BG and MLE on
      metabolic disorders and show that the combination of BG and MLE has synergetic
      effects.

PMID- 29023389
TI  - Upcycling Waste Lard Oil into Vertical Graphene Sheets by Inductively Coupled
      Plasma Assisted Chemical Vapor Deposition.
AB  - Vertical graphene (VG) sheets were single-step synthesized via inductively
      coupled plasma (ICP)-enhanced chemical vapor deposition (PECVD) using waste lard
      oil as a sustainable and economical carbon source. Interweaved few-layer VG
      sheets, H2, and other hydrocarbon gases were obtained after the decomposition of
      waste lard oil. The influence of parameters such as temperature, gas proportion,
      ICP power was investigated to tune the nanostructures of obtained VG, which
      indicated that a proper temperature and H2 concentration was indispensable for
      the synthesis of VG sheets. Rich defects of VG were formed with a high I D / I G
      ratio (1.29), consistent with the dense edges structure observed in electron
      microscopy. Additionally, the morphologies, crystalline degree, and wettability
      of nanostructure carbon induced by PECVD and ICP separately were comparatively
      analyzed. The present work demonstrated the potential of our PECVD recipe to
      synthesize VG from abundant natural waste oil, which paved the way to upgrade the
      low-value hydrocarbons into advanced carbon material.

PMID- 29023388
TI  - The Association of Vitamin D Status with Disease Activity in a Cohort of Crohn's
      Disease Patients in Canada.
AB  - We determined the association between vitamin D status as 25hydroxyvitamin D
      [25(OH)D] and disease activity in a cohort of 201 Crohn's Disease (CD) patients
      in Saskatoon, Canada over three years. The association between high-sensitivity C
      reactive protein (hs-CRP) and 25(OH)D and several disease predictors were
      evaluated by the generalized estimating equation (GEE) over three time-point
      measurements. A GEE binary logistic regression test was used to evaluate the
      association between vitamin D status and the Harvey-Bradshaw Index (HBI). The
      deficient vitamin D group (<=29 nmol/L) had significantly higher mean hs-CRP
      levels compared with the three other categories of vitamin D status (p < 0.05).
      CRP was significantly lower in all of the other groups compared with the vitamin
      D-deficient group, which had Coef. = 12.8 units lower (95% CI -19.8, -5.8), Coef.
      7.85 units (95% CI -14.9, -0.7), Coef. 9.87 units (95% CI -17.6, -2.0) for the
      vitamin D insufficient, adequate, and optimal groups, respectively. The vitamin D
      status was associated with the HBI active disease category. However, the
      difference in the odds ratio compared with the reference category of deficient
      vitamin D category was only significant in the insufficient category (odds ratio
      = 3.45, p = 0.03, 95% CI 1.0, 10.8). Vitamin D status was inversely associated
      with indicators of disease activity in Crohn's disease, particularly with the
      objective measures of inflammation.

PMID- 29023391
TI  - Experimental Analysis and Mathematical Modeling on Mg-Li Alloy Sheets with Three
      Crystal Structures during Cold Rolling and Heat Treatment.
AB  - The microstructural evolution, mechanical properties, and mathematical
      relationship of an alpha, alpha + beta, and beta phase Mg-Li alloy during the
      cold rolling and annealing process were investigated. The results showed that the
      increased Li element gradually transformed the Mg matrix structure from hcp to
      bcc. Simultaneously, the alloy plasticity was improved remarkably during cold
      rolling. In the annealing process, a sort of abnormal grain growth was found in
      Mg-11Li-3Al-2Zn-0.2Y, but was not detected in Mg-5Li-3Al-2Zn-0.2Y and Mg-8Li-3Al
      2Zn-0.2Y. Moreover, the mechanical properties of alloy were evidently improved
      through a kind of solid solution in the beta matrix. To accurately quantify this
      strengthening effect, the method of mathematical modeling was used to determine
      the relationship between strength and multiple factors.

PMID- 29023390
TI  - Electrospun Zein/Gelatin Scaffold-Enhanced Cell Attachment and Growth of Human
      Periodontal Ligament Stem Cells.
AB  - Periodontitis is a widespread dental disease affecting 10 to 15% of worldwide
      adult population, yet the current treatments are far from satisfactory. The human
      periodontal ligament stem cell is a promising potential seed cell population type
      in cell-based therapy and tissue regeneration, which require appropriate scaffold
      to provide a mimic extracellular matrix. Zein, a native protein derived from
      corn, has an excellent biodegradability, and therefore becomes a hotspot on
      research and application in the field of biomaterials. However, the high
      hydrophobicity of zein is unfavorable for cell adhesion and thus greatly limits
      its use. In this study, we fabricate co-electrospun zein/gelatin fiber scaffolds
      in order to take full advantages of the two natural materials and electrospun
      fiber structure. Zein and gelatin in four groups of different mass ratios
      (100:00, 100:20, 100:34, 100:50), and dissolved the mixtures in 1,1,1,3,3,3
      hexafluoro-2-propanol, then produced membranes by electrospinning. The results
      showed that the scaffolds were smooth and homogeneous, as shown in scanning
      electron micrographs. The diameter of hybrid fibers was increased from 69 +/- 22
      nm to 950 +/- 356 nm, with the proportion of gelatin increase. The cell affinity
      of zein/gelatin nanofibers was evaluated by using human periodontal ligament stem
      cells. The data showed that hydrophilicity and cytocompatibility of zein
      nanofibers were improved by blended gelatin. Taken together, our results
      indicated that the zein/gelatin co-electrospun fibers had sufficient mechanical
      properties, satisfied cytocompatibility, and can be utilized as biological
      scaffolds in the field of tissue regeneration.

PMID- 29023392
TI  - Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition
      Activity of Tetrahydrocurcumin and Other Curcuminoids.
AB  - Tetrahydrocurcumin (THC), curcumin and calebin-A are curcuminoids found in
      turmeric (Curcuma longa). Curcuminoids have been established to have a variety of
      pharmacological activities and are used as natural health supplements. The
      purpose of this study was to identify the metabolism, excretion, antioxidant,
      anti-inflammatory and anticancer properties of these curcuminoids and to
      determine disposition of THC in rats after oral administration. We developed a
      UHPLC-MS/MS assay for THC in rat serum and urine. THC shows multiple
      redistribution phases with corresponding increases in urinary excretion rate. In
      vitro antioxidant activity, histone deacetylase (HDAC) activity, histone
      acetyltransferase (HAT) activity and anti-inflammatory inhibitory activity were
      examined using commercial assay kits. Anticancer activity was determined in Sup
      T1 lymphoma cells. Our results indicate THC was poorly absorbed after oral
      administration and primarily excreted via non-renal routes. All curcuminoids
      exhibited multiple pharmacological effects in vitro, including potent antioxidant
      activity as well as inhibition of CYP2C9, CYP3A4 and lipoxygenase activity
      without affecting the release of TNF-alpha. Unlike curcumin and calebin-A, THC
      did not inhibit HDAC1 and PCAF and displayed a weaker growth inhibition activity
      against Sup-T1 cells. We show evidence for the first time that curcumin and
      calebin-A inhibit HAT and PCAF, possibly through a Michael-addition mechanism.

PMID- 29023394
TI  - Carbon-Based Oxamate Cobalt(III) Complexes as Bioenzyme Mimics for Contaminant
      Elimination in High Backgrounds of Complicated Constituents.
AB  - Complex wastewater with massive components is now a serious environmental issue
      facing humanity. Selective removal of low-concentration contaminants in mixed
      constituents holds great promise for increasing water supplies. Bioenzymes like
      horseradish peroxidase exhibit oxidizing power and selectivity. Here, we
      manufactured its mimic through immobilizing non-heme oxamate anionic cobalt(III)
      complex ([CoIII(opba)]-, opba = o-phenylenebis(oxamate)) onto pyridine (Py)
      modified multiwalled carbon nanotubes ([CoIII(opba)]--Py-MWCNTs, MWCNTs =
      multiwalled carbon nanotubes), where MWCNTs captured substrates and Py functioned
      as the fifth ligand. We chose typical azo dye (C.I. Acid Red 1) and antibiotic
      (ciprofloxacin) as model substrates. Without *OH, this catalyst could detoxify
      target micropollutants efficiently at pH from 8 to 11. It also remained efficient
      in repetitive tests, and the final products were non-poisonous OH-containing
      acids. Combined with radical scavenger tests and electron paramagnetic resonance
      result, we speculated that high-valent cobalt-oxo active species and oxygen atom
      transfer reaction dominated in the reaction pathway. According to density
      functional theory calculations, the electron spin density distribution order
      showed that electron-withdrawing ligand was beneficial for inward pulling the
      excess electron and lowering the corresponding energy levels, achieving an
      electrophilic-attack enhancement of the catalyst. With target removal property
      and recyclability, this catalyst is prospective in water detoxication.

PMID- 29023393
TI  - Flavanol-Rich Cocoa Powder Interacts with Lactobacillus rhamnossus LGG to Alter
      the Antibody Response to Infection with the Parasitic Nematode Ascaris suum.
AB  - Consumption of the probiotic bacteria LactobacillusrhamnosusLGG and flavanol-rich
      cocoa have purported immune modulating effects. This study compared the host
      response to infection with Ascaris suum in three-month-old pigs fed a standard
      growth diet supplemented with a vehicle control: LGG, cocoa powder (CP) or LGG +
      CP. Pigs were inoculated with infective A. suum eggs during Week 5 of dietary
      treatment and euthanized 17 days later. Lactobacillus abundance was increased in
      pigs fed LGG or LGG + CP. Specific anti-A. suum IgG2 antibodies were decreased (p
      < 0.05) in LGG + CP-fed pigs compared to pigs fed CP alone. Pigs fed LGG had
      significantly reduced expression (p < 0.05) of Eosinophil peroxidase (EPX),
      Interleukin 13 (IL-13), Eotaxin 3 (CCL26), Toll-like receptor 2 (TLR2), TLR4, and
      TLR9 and Interleukin-1Beta (IL1B) in the tracheal-bronchial lymph node (TBLN)
      independent of CP treatment. These results suggested that feeding LGG
      significantly reduced the localized prototypical Th2-related markers of infection
      with A. suum in the TBLN. Although feeding CP does not appear to affect the A.
      suum-induced Th2-associated cytokine response, feeding LGG + CP reduced anti-A.
      suum antibodies and delayed intestinal expulsion of parasitic larvae from the
      intestine.

PMID- 29023395
TI  - Validation of Molecular Dynamics Simulations for Prediction of Three-Dimensional
      Structures of Small Proteins.
AB  - Although various higher-order protein structure prediction methods have been
      developed, almost all of them were developed based on the three-dimensional (3D)
      structure information of known proteins. Here we predicted the short protein
      structures by molecular dynamics (MD) simulations in which only Newton's
      equations of motion were used and 3D structural information of known proteins was
      not required. To evaluate the ability of MD simulationto predict protein
      structures, we calculated seven short test protein (10-46 residues) in the
      denatured state and compared their predicted and experimental structures. The
      predicted structure for Trp-cage (20 residues) was close to the experimental
      structure by 200-ns MD simulation. For proteins shorter or longer than Trp-cage,
      root-mean square deviation values were larger than those for Trp-cage. However,
      secondary structures could be reproduced by MD simulations for proteins with 10
      34 residues. Simulations by replica exchange MD were performed, but the results
      were similar to those from normal MD simulations. These results suggest that
      normal MD simulations can roughly predict short protein structures and 200-ns
      simulations are frequently sufficient for estimating the secondary structures of
      protein (approximately 20 residues). Structural prediction method using only
      fundamental physical laws are useful for investigating non-natural proteins, such
      as primitive proteins and artificial proteins for peptide-based drug delivery
      systems.

PMID- 29023397
TI  - An Anomalous Noise Events Detector for Dynamic Road Traffic Noise Mapping in Real
      Life Urban and Suburban Environments.
AB  - One of the main aspects affecting the quality of life of people living in urban
      and suburban areas is their continued exposure to high Road Traffic Noise (RTN)
      levels. Until now, noise measurements in cities have been performed by
      professionals, recording data in certain locations to build a noise map
      afterwards. However, the deployment of Wireless Acoustic Sensor Networks (WASN)
      has enabled automatic noise mapping in smart cities. In order to obtain a
      reliable picture of the RTN levels affecting citizens, Anomalous Noise Events
      (ANE) unrelated to road traffic should be removed from the noise map computation.
      To this aim, this paper introduces an Anomalous Noise Event Detector (ANED)
      designed to differentiate between RTN and ANE in real time within a predefined
      interval running on the distributed low-cost acoustic sensors of a WASN. The
      proposed ANED follows a two-class audio event detection and classification
      approach, instead of multi-class or one-class classification schemes, taking
      advantage of the collection of representative acoustic data in real-life
      environments. The experiments conducted within the DYNAMAP project, implemented
      on ARM-based acoustic sensors, show the feasibility of the proposal both in terms
      of computational cost and classification performance using standard Mel cepstral
      coefficients and Gaussian Mixture Models (GMM). The two-class GMM core classifier
      relatively improves the baseline universal GMM one-class classifier F1 measure by
      18.7% and 31.8% for suburban and urban environments, respectively, within the 1-s
      integration interval. Nevertheless, according to the results, the classification
      performance of the current ANED implementation still has room for improvement.

PMID- 29023396
TI  - Diversity and Antimicrobial Potential of Predatory Bacteria from the Peruvian
      Coastline.
AB  - The microbiome of three different sites at the Peruvian Pacific coast was
      analyzed, revealing a lower bacterial biodiversity at Isla Foca than at Paracas
      and Manglares, with 89 bacterial genera identified, as compared to 195 and 173
      genera, respectively. Only 47 of the bacterial genera identified were common to
      all three sites. In order to obtain promising strains for the putative production
      of novel antimicrobials, predatory bacteria were isolated from these sampling
      sites, using two different bait organisms. Even though the proportion of
      predatory bacteria was only around 0.5% in the here investigated environmental
      microbiomes, by this approach in total 138 bacterial strains were isolated as
      axenic culture. 25% of strains showed antibacterial activity, thereby nine
      revealed activity against clinically relevant methicillin resistant
      Staphylococcus aureus (MRSA) and three against enterohemorrhagic Escherichia coli
      (EHEC) strains. Phylogeny and physiological characteristics of the active strains
      were investigated. First insights into the chemical basis of the antibacterial
      activity indicated the biosynthetic production of the known compounds
      ariakemicin, kocurin, naphthyridinomycin, pumilacidins, resistomycin, and
      surfactin. However, most compounds remained elusive until now. Hence, the
      obtained results implicate that the microbiome present at the various habitats at
      the Peruvian coastline is a promising source for heterotrophic bacterial strains
      showing high potential for the biotechnological production of antibiotics.

PMID- 29023398
TI  - The Impact of Oxidative Stress on the Bone System in Response to the Space
      Special Environment.
AB  - The space special environment mainly includes microgravity, radiation, vacuum and
      extreme temperature, which seriously threatens an astronaut's health. Bone loss
      is one of the most significant alterations in mammalians after long-duration
      habitation in space. In this review, we summarize the crucial roles of major
      factors-namely radiation and microgravity-in space in oxidative stress generation
      in living organisms, and the inhibitory effect of oxidative stress on bone
      formation. We discussed the possible mechanisms of oxidative stress-induced
      skeletal involution, and listed some countermeasures that have therapeutic
      potentials for bone loss via oxidative stress antagonism. Future research for
      better understanding the oxidative stress caused by space environment and the
      development of countermeasures against oxidative damage accordingly may
      facilitate human beings to live more safely in space and explore deeper into the
      universe.

PMID- 29023400
TI  - Electrostatic Self-Assembled Chitosan-Pectin Nano- and Microparticles for Insulin
      Delivery.
AB  - A polyelectrolyte complex system of chitosan-pectin nano- and microparticles was
      developed to encapsulate the hormone insulin. The aim of this work was to obtain
      small particles for oral insulin delivery without chemical crosslinkers based on
      natural and biodegradable polysaccharides. The nano- and microparticles were
      developed using chitosans (with different degrees of acetylation: 15.0% and
      28.8%) and pectin solutions at various charge ratios (n+/n- given by the
      chitosan/pectin mass ratio) and total charge. Nano- and microparticles were
      characterized regarding particle size, zeta potential, production yield,
      encapsulation efficiency, stability in different media, transmission electron
      microscopy and cytotoxicity assays using Caco-2 cells. The insulin release was
      evaluated in vitro in simulated gastric and intestinal media. Small-sized
      particles (~240-~1900 nm) with a maximum production yield of ~34.0% were
      obtained. The highest encapsulation efficiency (~62.0%) of the system was
      observed at a charge ratio (n+/n-) 5.00. The system was stable in various media,
      particularly in simulated gastric fluid (pH 1.2). Transmission electron
      microscopy (TEM) analysis showed spherical shape particles when insulin was added
      to the system. In simulated intestinal fluid (pH 6.8), controlled insulin release
      occurred over 2 h. In vitro tests indicated that the proposed system presents
      potential as a drug delivery for oral administration of bioactive peptides.

PMID- 29023402
TI  - Comparison of the Percentage of Voids in the Canal Filling of a Calcium Silicate
      Based Sealer and Gutta Percha Cones Using Two Obturation Techniques.
AB  - This study evaluated the root-filling quality of a calcium silicate-based sealer
      and gutta percha (GP) cones by measuring the percentage of voids. Twenty
      artificial molar teeth were divided into two groups: one obturated using the
      single-cone (SC) technique, and the other using the continuous wave (CW)
      technique. Obturation was performed with GP cones and Endoseal MTA (mineral
      trioxide aggregate, Maruchi, Wonju, Korea). Obturated teeth were scanned using
      microcomputed tomography, and the percentage of void volume was calculated in the
      apical and coronal areas. A linear mixed model was used to determine the
      differences between the two techniques (p < 0.05). The percentage of voids
      between the filling materials and root canal walls was not significantly
      different between the two obturation methods (p > 0.05), except for the CW group,
      which demonstrated a significantly higher void volume in the coronal area of the
      distal canal (p < 0.05). The percentage of voids inside the filling material was
      significantly higher in the CW groups for all of the comparisons (p < 0.05),
      except in the apical area of the distal canal (p > 0.05). The voids between the
      filling material and canal wall in the apical area were not significantly
      different between the two techniques.

PMID- 29023401
TI  - Effects of Sorghum Malting on Colour, Major Classes of Phenolics and Individual
      Anthocyanins.
AB  - Sorghum (Sorghum bicolor) grain contains many health-promoting phytochemicals,
      including a broad range of phenolic compounds. Malting of cereal grains is known
      to increase the bioavailability of macro- and micronutrients. However, the
      detailed effects of malting on sorghum grain anthocyanins, a major class of
      phenolics that influence the taste and colour of sorghum-based foods, requires
      further investigation. Eight commercial sorghum hybrids harvested from three
      regions in eastern Australia were malted and analysed for colour, tannin content,
      total phenolic content (TPC), flavan-4-ols, total flavonoids, total anthocyanins
      and 3-deoxyanthocyanins. Grains of all the sorghums were found to be tannin-free.
      Malting decreased the TPC of all samples. For TPC, the grand means among all the
      sorghum cultivars for raw and malted grain were 2.77 and 2.48 mg gallic acid
      equivalents (GAE)/g, respectively. For flavan-4-ols, the grand means for raw and
      malted sorghum grains were 2.98 and 2.23 abs/mL/g, respectively. Remarkably,
      total anthocyanin levels more than doubled upon malting whereas total flavonoid
      levels decreased by 12%. The average abundance of 3-deoxyanthocyanins in raw
      sorghum grains increased for about 8-fold upon malting. Our results will be
      valuable for sorghum breeders in the selection of lines for specific end uses and
      for food scientists developing sorghum-based products.

PMID- 29023399
TI  - Novel Anti-Tuberculosis Nanodelivery Formulation of Ethambutol with Graphene
      Oxide.
AB  - Tuberculosis (TB) is a bacterial disease responsible for millions of infections
      and preventable deaths each year. Its treatment is complicated by patients'
      noncompliance due to dosing frequency, lengthy treatment, and adverse side
      effects associated with current chemotherapy. However, no modifications to the
      half-a-century old standard chemotherapy have been made based on a
      nanoformulation strategy to improve pharmacokinetic efficacy. In this study, we
      have designed a new nanodelivery formulation, using graphene oxide as the
      nanocarrier, loaded with the anti-TB antibiotic, ethambutol. The designed
      formulation was characterized using a number of molecular analytical techniques.
      It was found that sustained release of the drug resulted in better
      bioavailability. In addition, the designed formulation demonstrated high
      biocompatibility with mouse fibroblast cells. The anti-TB activity of the
      nanodelivery formulation was determined using whole-cell resazurin microtiter
      plate assay, modified-spot culture growth inhibition assay, and biofilm
      inhibition assay. The nanodelivery formulation showed good anti-mycobacterial
      activity. The anti-mycobacterial activity of Ethambutol was unaffected by the
      drug loading and release process. The results of this study demonstrated the
      potential of this new nanodelivery formulation strategy to be considered for
      modifying existing chemotherapy to yield more efficacious antibiotic treatment
      against TB.

PMID- 29023403
TI  - Electrodermal Activity Sensor for Classification of Calm/Distress Condition.
AB  - This article introduces a new and unobtrusive wearable monitoring device based on
      electrodermal activity (EDA) to be used in health-related computing systems. This
      paper introduces the description of the wearable device capable of acquiring the
      EDA of a subject in order to detect his/her calm/distress condition from the
      acquired physiological signals. The lightweight wearable device is placed in the
      wrist of the subject to allow continuous physiological measurements. With the aim
      of validating the correct operation of the wearable EDA device, pictures from the
      International Affective Picture System are used in a control experiment involving
      fifty participants. The collected signals are processed, features are extracted
      and a statistical analysis is performed on the calm/distress condition
      classification. The results show that the wearable device solely based on EDA
      signal processing reports around 89% accuracy when distinguishing calm condition
      from distress condition.

PMID- 29023404
TI  - Novel Synthesis of Core-Shell Silica Nanoparticles for the Capture of Low
      Molecular Weight Proteins and Peptides.
AB  - Silica nanoparticles were functionalized with immobilized molecular bait,
      Cibacron Blue, and a porous polymeric bis-acrylamide shell. These nanoparticles
      represent a new alternative to capture low molecular weight (LMW)
      proteins/peptides, that might be potential biomarkers. Functionalized core-shell
      silica nanoparticles (FCSNP) presented a size distribution of 243.9 +/- 11.6 nm
      and an estimated surface charge of -38.1 +/- 0.9 mV. The successful attachment of
      compounds at every stage of synthesis was evidenced by ATR-FTIR. The capture of
      model peptides was determined by mass spectrometry, indicating that only the
      peptide with a long sequence of hydrophobic amino acids (alpha zein 34-mer)
      interacted with the molecular bait. FCSNP excluded the high molecular weight
      protein (HMW), BSA, and captured LMW proteins (myoglobin and aprotinin), as
      evidenced by SDS-PAGE. Functionalization of nanoparticles with Cibacron Blue was
      crucial to capture these molecules. FCSNP were stable after twelve months of
      storage and maintained a capacity of 3.1-3.4 ug/mg.

PMID- 29023405
TI  - The Aspergillus flavus Homeobox Gene, hbx1, is Required for Development and
      Aflatoxin Production.
AB  - Homeobox proteins, a class of well conserved transcription factors, regulate the
      expression of targeted genes, especially those involved in development. In
      filamentous fungi, homeobox genes are required for normal conidiogenesis and
      fruiting body formation. In the present study, we identified eight homeobox (hbx)
      genes in the aflatoxin-producing ascomycete, Aspergillus flavus, and determined
      their respective role in growth, conidiation and sclerotial production.
      Disruption of seven of the eight genes had little to no effect on fungal growth
      and development. However, disruption of the homeobox gene AFLA_069100, designated
      as hbx1, in two morphologically different A. flavus strains, CA14 and AF70,
      resulted in complete loss of production of conidia and sclerotia as well as
      aflatoxins B1 and B2, cyclopiazonic acid and aflatrem. Microscopic examination
      showed that the Deltahbx1 mutants did not produce conidiophores. The inability of
      Deltahbx1 mutants to produce conidia was related to downregulation of brlA
      (bristle) and abaA (abacus), regulatory genes for conidiophore development. These
      mutants also had significant downregulation of the aflatoxin pathway biosynthetic
      genes aflC, aflD, aflM and the cluster-specific regulatory gene, aflR. Our
      results demonstrate that hbx1 not only plays a significant role in controlling A.
      flavus development but is also critical for the production of secondary
      metabolites, such as aflatoxins.

PMID- 29023406
TI  - Facile and Green Synthesis of Saturated Cyclic Amines.
AB  - Single-nitrogen containing saturated cyclic amines are an important part of both
      natural and synthetic bioactive compounds. A number of methodologies have been
      developed for the synthesis of aziridines, azetidines, pyrrolidines, piperidines,
      azepanes and azocanes. This review highlights some facile and green synthetic
      routes for the synthesis of unsubstituted, multisubstituted and highly
      functionalized saturated cyclic amines including one-pot, microwave assisted,
      metal-free, solvent-free and in aqueous media.

PMID- 29023407
TI  - Halogenated 1-Hydroxynaphthalene-2-Carboxanilides Affecting Photosynthetic
      Electron Transport in Photosystem II.
AB  - Series of seventeen new multihalogenated 1-hydroxynaphthalene-2-carboxanilides
      was prepared and characterized. All the compounds were tested for their activity
      related to the inhibition of photosynthetic electron transport (PET) in spinach
      (Spinacia oleracea L.) chloroplasts. 1-Hydroxy-N-phenylnaphthalene-2-carboxamides
      substituted in the anilide part by 3,5-dichloro-, 4-bromo-3-chloro-, 2,5-dibromo-
      and 3,4,5-trichloro atoms were the most potent PET inhibitors (IC50 = 5.2, 6.7,
      7.6 and 8.0 uM, respectively). The inhibitory activity of these compounds depends
      on the position and the type of halogen substituents, i.e., on lipophilicity and
      electronic properties of individual substituents of the anilide part of the
      molecule. Interactions of the studied compounds with chlorophyll a and aromatic
      amino acids present in pigment-protein complexes mainly in PS II were documented
      by fluorescence spectroscopy. The section between P680 and plastoquinone QB in
      the PET chain occurring on the acceptor side of PS II can be suggested as the
      site of action of the compounds. The structure-activity relationships are
      discussed.

PMID- 29023408
TI  - Rational Design of Nucleoside-Bile Acid Conjugates Incorporating a Triazole
      Moiety for Anticancer Evaluation and SAR Exploration.
AB  - Herein we report a study on the synthesis and biological evaluation of a library
      of nucleoside-bile acid conjugates prepared by combining 2'-deoxyadenosine, 2'
      deoxyguanosine, 2'-deoxyuridine as well as adenosine and guanosine derivatives
      with cheno-, urso-, nor-cheno-, nor-urso- and taurourso-desoxycholic acid
      derivatives by means of the click reaction. The new nucleoside-bile acid
      conjugates incorporating a triazole moiety were tested in vitro against leukemic
      K562 and HCT116 colon carcinoma, as well as on normal fibroblast cells. Six
      compounds displayed interesting anti-proliferative activity against the selected
      cancer lines and no cytotoxic effects against normal fibroblasts. A possible
      structure activity relationship was also investigated.

PMID- 29023409
TI  - A High Stability Time Difference Readout Technique of RTD-Fluxgate Sensors.
AB  - The performance of Residence Times Difference (RTD)-fluxgate sensors is closely
      related to the time difference readout technique. The noise of the induction
      signal affects the quality of the output signal of the following circuit and the
      time difference detection, so the stability of the sensor is limited. Based on
      the analysis of the uncertainty of the RTD-fluxgate using the Bidirectional
      Magnetic Saturation Time Difference (BMSTD) readout scheme, the relationship
      between the saturation state of the magnetic core and the target (DC) magnetic
      field is studied in this article. It is proposed that combining the excitation
      and induction signals can provide the Negative Magnetic Saturation Time (NMST),
      which is a detection quantity used to measure the target magnetic field. Also, a
      mathematical model of output response between NMST and the target magnetic field
      is established, which analyzes the output NMST and sensitivity of the RTD
      fluxgate sensor under different excitation conditions and is compared to the
      BMSTD readout scheme. The experiment results indicate that this technique can
      effectively reduce the noise influence. The fluctuation of time difference is
      less than +/-0.1 MUs in a target magnetic field range of +/-5 * 104 nT. The
      accuracy and stability of the sensor are improved, so the RTD-fluxgate using the
      readout technique of high stability time difference is suitable for detecting
      weak magnetic fields.

PMID- 29023411
TI  - Scientific Study of Gentiana kurroo Royle.
AB  - The present investigation was carried out to review and highlight the potential
      phytochemicals and medicinal phenomena of the critically endangered medicinal
      plant, Gentiana kurroo Royle of the western and north-western Himalayas. The
      medicinal plant is heavily exploited for root and rhizome. Due to its endemic
      nature and the high rate of exploitation from its natural habitat, this species
      had become critically endangered. The phytochemical screening of the plant
      revealed that the plant contains some vital phyto-constituents (iridoids,
      xanthones, C-glucoxanthone mangiferin, and C-glucoflavones) that have a medicinal
      value for various acute and chronic diseases. Several researchers have carried
      out experimental work to validate the folkloric use of the medicinal plant for
      different ailments like antibacterial, antioxidant, anti-arthritic, anti
      inflammatory, analgesic activities and anti-diabetic activity. However, it is yet
      to be confirmed the antifungal activity of the same plant. Because of endemic
      nature and high rate of exploitation there is need for alternative method called
      bio-prospecting of Endophytes from the plant, to carry out the production and
      characterization of bioactive metabolites for pharmacological uses and can become
      a conservative tool for the medicinal plant.

PMID- 29023410
TI  - Long Term Osmotic Mini Pump Treatment with Alpha-MSH Improves Myocardial Function
      in Zucker Diabetic Fatty Rats.
AB  - The present investigation evaluates the cardiovascular effects of the
      anorexigenic mediator alpha-melanocyte stimulating hormone (MSH), in a rat model
      of type 2 diabetes. Osmotic mini pumps delivering MSH or vehicle, for 6 weeks,
      were surgically implanted in Zucker Diabetic Fatty (ZDF) rats. Serum parameters,
      blood pressure, and weight gain were monitored along with oral glucose tolerance
      (OGTT). Echocardiography was conducted and, following sacrifice, the effects of
      treatment on ischemia/reperfusion cardiac injury were assessed using the isolated
      working heart method. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      activity was measured to evaluate levels of oxidative stress, and force
      measurements were performed on isolated cardiomyocytes to determine calcium
      sensitivity, active tension and myofilament co-operation. Vascular status was
      also evaluated on isolated arterioles using a contractile force measurement
      setup. The echocardiographic parameters ejection fraction (EF), fractional
      shortening (FS), isovolumetric relaxation time (IVRT), mitral annular plane
      systolic excursion (MAPSE), and Tei-index were significantly better in the MSH
      treated group compared to ZDF controls. Isolated working heart aortic and
      coronary flow was increased in treated rats, and higher Hill coefficient
      indicated better myofilament co-operation in the MSH-treated group. We conclude
      that MSH improves global heart functions in ZDF rats, but these effects are not
      related to the vascular status.

PMID- 29023412
TI  - Post-Translational Modification of Human Histone by Wide Tolerance of
      Acetylation.
AB  - Histone acetylation adds an acetyl group on the lysine residue commonly found
      within the N-terminal tail protruding from the histone core of the nucleosome,
      and is important for chromosome structure and function in gene transcription and
      chromatin remodeling. Acetylation may also occur on other residues additional to
      lysine, but have not been thoroughly investigated at the proteomics level. Here
      we report a wide tolerance acetylation study mimicking the addition of 42 +/- 0.5
      Da delta mass modification on undefined amino acid residues of histones by
      shotgun proteomics using liquid chromatography-tandem mass spectrometry. A multi
      blind spectral alignment algorithm with a wide peptide tolerance revealed
      frequent occurrence of 42 +/- 0.5 Da modifications at lysine (K), serine (S) and
      threonine (T) residues in human histones from kidney tissues. Precision delta
      mass analysis identified acetylation (42.011 +/- 0.004 Da) and trimethylation
      (42.047 +/- 0.002 Da) modifications within the delta mass range. A specific
      antibody was produced to validate the acetylated T22 of human histone H3
      (H3T22ac) by immune assays. Thus, we demonstrated that the wide tolerance
      acetylation approach identified histone acetylation as well as modification
      variants commonly associated with acetylation at undefined residues additional to
      lysine.

PMID- 29023413
TI  - Diallylthiosulfinate (Allicin), a Volatile Antimicrobial from Garlic (Allium
      sativum), Kills Human Lung Pathogenic Bacteria, Including MDR Strains, as a
      Vapor.
AB  - Garlic (Allium sativum) has potent antimicrobial activity due to allicin
      (diallylthiosulfinate) synthesized by enzyme catalysis in damaged garlic tissues.
      Allicin gives crushed garlic its characteristic odor and its volatility makes it
      potentially useful for combating lung infections. Allicin was synthesized (>98%
      pure) by oxidation of diallyl disulfide by H2O2 using formic acid as a catalyst
      and the growth inhibitory effect of allicin vapor and allicin in solution to
      clinical isolates of lung pathogenic bacteria from the genera Pseudomonas,
      Streptococcus, and Staphylococcus, including multi-drug resistant (MDR) strains,
      was demonstrated. Minimal inhibitory (MIC) and minimal bactericidal
      concentrations (MBC) were determined and compared to clinical antibiotics using
      standard European Committee on Antimicrobial Susceptibility Testing (EUCAST)
      procedures. The cytotoxicity of allicin to human lung and colon epithelial and
      murine fibroblast cells was tested in vitro and shown to be ameliorated by
      glutathione (GSH). Similarly, the sensitivity of rat precision-cut lung slices
      (PCLS) to allicin was decreased by raising the [GSH] to the approximate blood
      plasma level of 1 mM. Because allicin inhibited bacterial growth as a vapor, it
      could be used to combat bacterial lung infections via direct inhalation. Since
      there are no volatile antibiotics available to treat pulmonary infections,
      allicin, particularly at sublethal doses in combination with oral antibiotics,
      could make a valuable addition to currently available treatments.

PMID- 29023414
TI  - 3,5,6,7,8,3',4'-Heptamethoxyflavone Ameliorates Depressive-Like Behavior and
      Hippocampal Neurochemical Changes in Chronic Unpredictable Mild Stressed Mice by
      Regulating the Brain-Derived Neurotrophic Factor: Requirement for ERK Activation.
AB  - We previously reported that the subcutaneous administration of 3,5,6,7,8,3',4'
      heptamethoxyflavone (HMF), a citrus polymethoxyflavone, attenuated depressive
      like behavior and increased the expression of brain-derived neurotrophic factor
      (BDNF) in the hippocampus of a corticosterone-induced depression-like mouse
      model. We herein demonstrated that (1) HMF was detectable in the brain 10 and 30
      min after its oral administration, (2) orally administered HMF improved chronic
      unpredictable mild stress (CUMS)-induced pathological conditions, including body
      weight loss and depressive-like behavior, and CUMS-induced neurochemical changes,
      such as reduction in BDNF expression, decrease in neurogenesis, and decreased
      level of phosphorylated calcium-calmodulin-dependent protein kinase II in the
      hippocampus, and (3) these effects of HMF were inhibited by the pre
      administration of U0126, a mitogen-activated protein (MAP) kinase inhibitor.
      These results suggest that orally administered HMF is beneficial for the
      upregulation of BDNF in the hippocampus via the extracellular signal-regulated
      kinase1/2 (ERK1/2)/MAP system, which may account for its antidepression effects.

PMID- 29023415
TI  - Characterization, Function, and Transcriptional Profiling Analysis of 3-Hydroxy-3
      methylglutaryl-CoA Synthase Gene (GbHMGS1) towards Stresses and Exogenous Hormone
      Treatments in Ginkgo biloba.
AB  - 3-Hydroxy-3-methylglutaryl-CoA synthase (HMGS) is one of the rate-limiting
      enzymes in the mevalonate pathway as it catalyzes the condensation of acetoacetyl
      CoA to form 3-hydroxy-3-methylglutaryl-CoA. In this study, A HMGS gene
      (designated as GbHMGS1) was cloned from Ginkgo biloba for the first time. GbHMGS1
      contained a 1422-bp open-reading frame encoding 474 amino acids. Comparative and
      bioinformatics analysis revealed that GbHMGS1 was extensively homologous to HMGSs
      from other plant species. Phylogenetic analysis indicated that the GbHMGS1
      belonged to the plant HMGS superfamily, sharing a common evolutionary ancestor
      with other HMGSs, and had a further relationship with other gymnosperm species.
      The yeast complement assay of GbHMGS1 in HMGS-deficient Saccharomyces cerevisiae
      strain YSC6274 demonstrated that GbHMGS1 gene encodes a functional HMGS enzyme.
      The recombinant protein of GbHMGS1 was successfully expressed in E. coli. The in
      vitro enzyme activity assay showed that the kcat and Km values of GbHMGS1 were
      195.4 min-1 and 689 MUM, respectively. GbHMGS1 was constitutively expressed in
      all tested tissues, including the roots, stems, leaves, female flowers, male
      flowers and fruits. The transcript accumulation for GbHMGS1 was highest in the
      leaves. Expression profiling analyses revealed that GbHMGS1 expression was
      induced by abiotic stresses (ultraviolet B and cold) and hormone treatments
      (salicylic acid, methyl jasmonate, and ethephon) in G. biloba, indicating that
      GbHMGS1 gene was involved in the response to environmental stresses and plant
      hormones.

PMID- 29023419
TI  - Synthesis and Biological Activity of Novel (Z)- and (E)-Verbenone Oxime Esters.
AB  - Twenty-seven (Z)- and (E)-verbenone derivatives bearing an oxime ester moiety
      were designed and synthesized in search of novel bioactive molecules. Their
      structures were confirmed by UV-Vis, FTIR, NMR, ESI-MS, and elemental analysis.
      The antifungal and herbicidal activities of the target compounds were
      preliminarily evaluated. As a result, compound (E)-4n (R = beta-pyridyl)
      exhibited excellent antifungal activity with growth inhibition percentages of
      92.2%, 80.0% and 76.3% against Alternaria solani, Physalospora piricola, and
      Cercospora arachidicola at 50 ug/mL, showing comparable or better antifungal
      activity than the commercial fungicide chlorothalonil with growth inhibition of
      96.1%, 75.0% and 73.3%, respectively, and 1.7-5.5-fold more growth inhibition
      than its stereoisomer (Z)-4n (R = beta-pyridyl) with inhibition rates of 22.6%,
      28.6% and 43.7%, respectively. In addition, seven compounds displayed significant
      growth inhibition activity of over 90% against the root of rape (Brassica
      campestris) at 100 ug/mL, exhibiting much better herbicidal activity than the
      commercial herbicide flumioxazin with a 63.0% growth inhibition. Among these
      seven compounds, compound (E)-4n (R = beta-pyridyl) inhibited growth by 92.1%,
      which was 1.7-fold more than its stereoisomer (Z)-4n (R = beta-pyridyl) which
      inhibited growth by 54.0%.

PMID- 29023416
TI  - Neuro-Coagulopathy: Blood Coagulation Factors in Central Nervous System Diseases.
AB  - Blood coagulation factors and other proteins, with modulatory effects or
      modulated by the coagulation cascade have been reported to affect the
      pathophysiology of the central nervous system (CNS). The protease-activated
      receptors (PARs) pathway can be considered the central hub of this regulatory
      network, mainly through thrombin or activated protein C (aPC). These proteins, in
      fact, showed peculiar properties, being able to interfere with synaptic
      homeostasis other than coagulation itself. These specific functions modulate
      neuronal networks, acting both on resident (neurons, astrocytes, and microglia)
      as well as circulating immune system cells and the extracellular matrix. The
      pleiotropy of these effects is produced through different receptors, expressed in
      various cell types, in a dose- and time-dependent pattern. We reviewed how these
      pathways may be involved in neurodegenerative diseases (amyotrophic lateral
      sclerosis, Alzheimer's and Parkinson's diseases), multiple sclerosis, ischemic
      stroke and post-ischemic epilepsy, CNS cancer, addiction, and mental health.
      These data open up a new path for the potential therapeutic use of the
      agonist/antagonist of these proteins in the management of several central nervous
      system diseases.

PMID- 29023420
TI  - Probiotics for the Prevention of Antibiotic-Associated Diarrhea in Outpatients-A
      Systematic Review and Meta-Analysis.
AB  - A common adverse effect of antibiotic use is diarrhea. Probiotics are living
      microorganisms, which, upon oral ingestion, may prevent antibiotic-associated
      diarrhea (AAD) by the normalization of an unbalanced gastrointestinal flora. The
      objective of this systematic review was to assess the benefits and harms of
      probiotics used for the prevention of AAD in an outpatient setting. A search of
      the PubMed database was conducted and yielded a total of 17 RCTs with 3631
      participants to be included in the review. A meta-analysis was conducted for the
      primary outcome: the incidence of AAD. The pooled results found that AAD was
      present in 8.0% of the probiotic group compared to 17.7% in the control group (RR
      0.49, 95% CI 0.36 to 0.66; I2 = 58%), and the species-specific results were
      similar regarding the probiotic strains L. rhamnosus GG and S. boulardii.
      However, the overall quality of the included studies was moderate. A meta
      analysis of the ten trials reporting adverse events demonstrated no statistically
      significant differences in the incidence of adverse events between the
      intervention and control group (RD 0.00, 95% CI -0.02 to 0.02, 2.363
      participants). The results suggests that probiotic use may be beneficial in the
      prevention of AAD among outpatients. Furthermore, the use of probiotics appears
      safe.

PMID- 29023418
TI  - Association between Stress and the HPA Axis in the Atopic Dermatitis.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is one of the body's neuroendocrine
      networks that responds to psychological stress (PS). In the skin, there exists a
      peripheral HPA axis similar to the central axis. Glucocorticoids (GCs) are key
      effector molecules of the HPA axis and are essential for cutaneous homeostasis.
      Atopic dermatitis (AD) is a condition typically characterized by a chronic
      relapsing course that often results in PS. HPA dysfunction is present in AD
      patients by the decreased response of GCs elevation to stress as compared to
      those unaffected by AD. Nevertheless, in skin, acute PS activates several
      metabolic responses that are of immediate benefit to the host. During the acute
      phase of PS, increased endogenous GCs have been shown to provide benefit rather
      than by aggravating cutaneous inflammatory dermatoses. However, a chronic T
      helper cell type 2 (Th2) predominant cytokine profile acts as a negative feedback
      loop to blunt the HPA axis response in AD. In this article, we reviewed the role
      of CRF, pro-opiomelanocortin (POMC)-derived peptides, GCs of the HPA, and 11beta
      hydroxysteroid dehydrogenase 1 (11beta-HSD1) in AD, with a discussion of the
      pathogenetic mechanisms of inflammation and skin barrier functions, including
      antimicrobial defense, and their association with PS.

PMID- 29023417
TI  - Control of NK Cell Activation by Immune Checkpoint Molecules.
AB  - The development of cancer and chronic infections is facilitated by many
      subversion mechanisms, among which enhanced expression of immune checkpoints
      molecules, such as programmed death-1 (PD-1) and cytotoxic T lymphocyte
      associated antigen 4 (CTLA-4), on exhausted T cells. Recently, immune checkpoint
      inhibitors have shown remarkable efficiency in the treatment of a number of
      cancers. However, expression of immune checkpoints on natural killer (NK) cells
      and its functional consequences on NK cell effector functions are much less
      explored. In this review, we focus on the current knowledge on expression of
      various immune checkpoints in NK cells, how it can alter NK cell-mediated
      cytotoxicity and cytokine production. Dissecting the role of these inhibitory
      mechanisms in NK cells is critical for the full understanding of the mode of
      action of immunotherapies using checkpoint inhibitors in the treatment of cancers
      and chronic infections.

PMID- 29023423
TI  - New Strategy for the Immobilization of Lipases on Glyoxyl-Agarose Supports:
      Production of Robust Biocatalysts for Natural Oil Transformation.
AB  - Immobilization on Glyoxyl-agarose support (Gx) is one of the best strategies to
      stabilize enzymes. However, the strategy is difficult to apply at neutral pH when
      most enzymes are stable and, even when possible, produces labile derivatives.
      This work contributes to overcoming this hurdle through a strategy that combines
      solid-phase amination, presence of key additives, and derivative basification. To
      this end, aminated industrial lipases from Candida artarctica (CAL), Thermomyces
      lunuginosus (TLL), and the recombinant Geobacillus thermocatenulatus (BTL2) were
      immobilized on Gx for the first time at neutral pH using anthranilic acid (AA) or
      DTT as additives (immobilization yields >70%; recovered activities 37.5-76.7%).
      The spectroscopic evidence suggests nucleophilic catalysis and/or adsorption as
      the initial lipase immobilization events. Subsequent basification drastically
      increases the stability of BTL2-glyoxyl derivatives under harsh conditions (t1/2,
      from 2.1-54.5 h at 70  degrees C; from 10.2 h-140 h in 80% dioxane). The novel
      BTL2-derivatives were active and selective in fish oil hydrolysis (1.0-1.8 MUmol
      of polyunsaturated fatty acids (PUFAs) min-1.g-1) whereas the selected TLL
      derivative was as active and stable in biodiesel production (fatty ethyl esters,
      EE) as the commercial Novozyme(r)-435 after ten reaction cycles (~70% EE).
      Therefore, the potential of the proposed strategy in producing suitable
      biocatalysts for industrial processes was demonstrated.

PMID- 29023421
TI  - Helicobacter pylori Vacuolating Toxin and Gastric Cancer.
AB  - Helicobacter pylori VacA is a channel-forming toxin unrelated to other known
      bacterial toxins. Most H. pylori strains contain a vacA gene, but there is marked
      variation among strains in VacA toxin activity. This variation is attributable to
      strain-specific variations in VacA amino acid sequences, as well as variations in
      the levels of VacA transcription and secretion. In this review, we discuss
      epidemiologic studies showing an association between specific vacA allelic types
      and gastric cancer, as well as studies that have used animal models to
      investigate VacA activities relevant to gastric cancer. We also discuss the
      mechanisms by which VacA-induced cellular alterations may contribute to the
      pathogenesis of gastric cancer.

PMID- 29023426
TI  - Nanometric MIL-125-NH2 Metal-Organic Framework as a Potential Nerve Agent
      Antidote Carrier.
AB  - The three-dimensional (3D) microporous titanium aminoterephthalate MIL-125-NH2
      (MIL: Material of Institut Lavoisier) was successfully isolated as monodispersed
      nanoparticles, which are compatible with intravenous administration, by using a
      simple, safe and low-cost synthetic approach (100  degrees C/32 h under
      atmospheric pressure) so that for the first time it could be considered for
      encapsulation and the release of drugs. The nerve agent antidote 2
      [(hydroxyimino)methyl]-1-methyl-pyridinium chloride (2-PAM or pralidoxime) was
      effectively encapsulated into the pores of MIL-125-NH2 as a result of the
      interactions between 2-PAM and the pore walls being mediated by pi-stacking and
      hydrogen bonds, as deduced from infrared spectroscopy and Monte Carlo simulation
      studies. Finally, colloidal solutions of MIL-125-NH2 nanoparticles exhibited
      remarkable stability in different organic media, aqueous solutions at different
      pH and under relevant physiological conditions over time (24 h). 2-PAM was
      rapidly released from the pores of MIL-125-NH2 in vitro.

PMID- 29023422
TI  - Plant Ribosome-Inactivating Proteins: Progesses, Challenges and Biotechnological
      Applications (and a Few Digressions).
AB  - Plant ribosome-inactivating protein (RIP) toxins are EC3.2.2.22 N-glycosidases,
      found among most plant species encoded as small gene families, distributed in
      several tissues being endowed with defensive functions against fungal or viral
      infections. The two main plant RIP classes include type I (monomeric) and type II
      (dimeric) as the prototype ricin holotoxin from Ricinus communis that is composed
      of a catalytic active A chain linked via a disulphide bridge to a B-lectin domain
      that mediates efficient endocytosis in eukaryotic cells. Plant RIPs can recognize
      a universally conserved stem-loop, known as the alpha-sarcin/ ricin loop or SRL
      structure in 23S/25S/28S rRNA. By depurinating a single adenine (A4324 in 28S rat
      rRNA), they can irreversibly arrest protein translation and trigger cell death in
      the intoxicated mammalian cell. Besides their useful application as potential
      weapons against infected/tumor cells, ricin was also used in bio-terroristic
      attacks and, as such, constitutes a major concern. In this review, we aim to
      summarize past studies and more recent progresses made studying plant RIPs and
      discuss successful approaches that might help overcoming some of the bottlenecks
      encountered during the development of their biomedical applications.

PMID- 29023425
TI  - Screening a Natural Product-Based Library against Kinetoplastid Parasites.
AB  - Kinetoplastid parasites cause vector-borne parasitic diseases including
      leishmaniasis, human African trypanosomiasis (HAT) and Chagas disease. These
      Neglected Tropical Diseases (NTDs) impact on some of the world's lowest
      socioeconomic communities. Current treatments for these diseases cause severe
      toxicity and have limited efficacy, highlighting the need to identify new
      treatments. In this study, the Davis open access natural product-based library
      was screened against kinetoplastids (Leishmania donovani DD8, Trypanosoma brucei
      brucei and Trypanosoma cruzi) using phenotypic assays. The aim of this study was
      to identify hit compounds, with a focus on improved efficacy, selectivity and
      potential to target several kinetoplastid parasites. The IC50 values of the
      natural products were obtained for L. donovani DD8, T. b. brucei and T. cruzi in
      addition to cytotoxicity against the mammalian cell lines, HEK-293, 3T3 and THP-1
      cell lines were determined to ascertain parasite selectivity. Thirty-one
      compounds were identified with IC50 values of <= 10 uM against the kinetoplastid
      parasites tested. Lissoclinotoxin E (1) was the only compound identified with
      activity across all three investigated parasites, exhibiting IC50 values < 5 uM.
      In this study, natural products with the potential to be new chemical starting
      points for drug discovery efforts for kinetoplastid diseases were identified.

PMID- 29023428
TI  - Effect of Nanoparticles on the Morphology, Thermal, and Electrical Properties of
      Low-Density Polyethylene after Thermal Aging.
AB  - This paper investigates the morphology, thermal, and electrical properties of
      LDPE (low-density polyethylene)-based nanocomposites after thermal aging. The
      FTIR (Fourier transform infrared spectroscopy) spectra results show that thermo
      oxidative reactions occur in neat LDPE and LDPE/SiO2 nanocomposites when the
      aging time is 35 days and in LDPE/MgO nanocomposites when the aging time is 77
      days. Specifically, LDPE/MgO nanocomposites delay the appearance of thermo
      oxidative reactions, showing anti-thermal aging ability. Furthermore,
      nanocomposites present lower onset degradation temperature than neat LDPE,
      showing better thermal stabilization. With regard to the electrical properties,
      nanocomposites maintain the ability to suppress space charge accumulation after
      thermal aging. Additionally, in comparison with SiO2 nanocomposites and neat
      LDPE, the permittivity of LDPE/MgO nanocomposites changes slightly after thermal
      aging. It is concluded that LDPE/MgO nanocomposites have better insulation
      properties than neat LDPE after thermal aging, which may be caused by the
      interface introduced by the nanoparticles.

PMID- 29023427
TI  - Hierarchical AuNPs-Loaded Fe3O4/Polymers Nanocomposites Constructed by
      Electrospinning with Enhanced and Magnetically Recyclable Catalytic Capacities.
AB  - Gold nanoparticles (AuNPs) have attracted widespread attention for their
      excellent catalytic activity, as well as their unusual physical and chemical
      properties. The main challenges come from the agglomeration and time-consuming
      separation of gold nanoparticles, which have greatly baffled the development and
      application in liquid phase selective reduction. To solve these problems, we
      propose the preparation of polyvinyl alcohol(PVA)/poly(acrylic acid)(PAA)/Fe3O4
      nanocomposites with loaded AuNPs. The obtained PVA/PAA/Fe3O4 composite membrane
      by electrospinning demonstrated high structural stability, a large specific
      surface area, and more active sites, which is conducive to promoting good
      dispersion of AuNPs on membrane surfaces. The subsequently prepared
      PVA/PAA/Fe3O4@AuNPs nanocomposites exhibited satisfactory nanostructures, robust
      thermal stability, and a favorable magnetic response for recycling. In addition,
      the PVA/PAA/Fe3O4@AuNPs nanocomposites showed a remarkable catalytic capacity in
      the catalytic reduction of p-nitrophenol and 2-nitroaniline solutions. In
      addition, the regeneration studies toward p-nitrophenol for different consecutive
      cycles demonstrate that the as-prepared PVA/PAA/Fe3O4@AuNPs nanocomposites have
      outstanding stability and recycling in catalytic reduction.

PMID- 29023429
TI  - MiR-150 Inhibits Cell Growth In Vitro and In Vivo by Restraining the
      RAB11A/WNT/beta-Catenin Pathway in Thyroid Cancer.
AB  - BACKGROUND Emerging evidence has shown that downregulation or upregulation of
      microRNAs (miRNAs) plays an important role in the development and progression of
      thyroid cancer (TC). However, the potential role of miR-150 and its biological
      function in TC remains largely unclear. MATERIAL AND METHODS Real-time polymerase
      chain reaction (RT-qPCR) was employed to detect the expression level of miR-150
      and RAB11A in human TC tissue and human normal thyroid tissue. MTT assay, colony
      formation assay, flow cytometry cell cycle, and apoptosis assay were used to
      investigate the role of miR-150 and RAB11A on the malignant phenotypes in vitro.
      Nude mouse xenograft assay and western blot assay was used to verify the function
      of miR-150 in vivo. Western blot assay and immunofluorescence assay were used to
      detect the activation of WNT/beta-catenin pathway mediated by miR-150 and RAB11A.
      EGFP reporter assay, RT-qPCR assay, and western blot assay were used to validate
      the regulation relationship. RESULTS This study demonstrated that miR-150
      expression in human TC tissues was markedly downregulated. Moreover,
      overexpression of miR-150 markedly inhibited cell proliferation via inducing the
      cell cycle arrest and promoting cell apoptosis by directly targeting RAB11A in
      vitro and suppressing tumor growth in vivo. However, overexpression of RAB11A
      promoted cell malignant phenotypes. In addition, miR-150 restrained the RAB11A
      mediated WNT/beta-catenin activation in TC cells. CONCLUSIONS miR-150 may
      function as a suppressor gene in TC cells by inhibiting the RAB11A/WNT/beta
      catenin pathway.

PMID- 29023430
TI  - Vaccination Coverage for Selected Vaccines, Exemption Rates, and Provisional
      Enrollment Among Children in Kindergarten - United States, 2016-17 School Year.
AB  - State and local school vaccination requirements help protect students and
      communities against vaccine-preventable diseases (1). CDC reports vaccination
      coverage and exemption data for children attending kindergarten (kindergartners)
      collected by federally funded immunization programs in the United States.* The
      typical age range for kindergartners is 4-6 years. Although vaccination
      requirements vary by state (the District of Columbia [DC] is counted as a state
      in this report.), the Advisory Committee on Immunization Practices recommends
      that children in this age range have received, among other vaccinations, 5 doses
      of diphtheria, tetanus, and acellular pertussis vaccine (DTaP), 2 doses of
      measles, mumps, and rubella vaccine (MMR), and 2 doses of varicella vaccine (2).
      This report summarizes 2016-17 school year MMR, DTaP, and varicella vaccination
      coverage reported by immunization programs in 49 states, exemptions in 50 states,
      and kindergartners provisionally enrolled or within a grace period in 27 states.
      Median vaccination coverage? was 94.5% for the state-required number of doses of
      DTaP; 94.0% for 2 doses of MMR; and 93.8% for 2 doses of varicella vaccine. The
      median percentage of kindergartners with an exemption from at least one vaccineS
      was 2.0%, similar to 2015-16 (1.9%). Median grace period and provisional
      enrollment was 2.0%. Vaccination coverage remains consistently high and
      exemptions low at state and national levels. Local-level vaccination coverage
      data provide opportunities for immunization programs to identify schools,
      districts, counties, or regions susceptible to vaccine-preventable diseases and
      for schools to address undervaccination through implementation of existing state
      and local vaccination policies (1) to protect communities through increased
      coverage.

PMID- 29023432
TI  - Erratum: Vol. 66, No. 35.

PMID- 29023424
TI  - Dietary Anthocyanins and Insulin Resistance: When Food Becomes a Medicine.
AB  - Insulin resistance is an abnormal physiological state that occurs when insulin
      from pancreatic beta-cells is unable to trigger a signal transduction pathway in
      target organs such as the liver, muscles and adipose tissues. The loss of insulin
      sensitivity is generally associated with persistent hyperglycemia (diabetes),
      hyperinsulinemia, fatty acids and/or lipid dysregulation which are often
      prevalent under obesity conditions. Hence, insulin sensitizers are one class of
      drugs currently employed to treat diabetes and associated metabolic disorders. A
      number of natural products that act through multiple mechanisms have also been
      identified to enhance insulin sensitivity in target organs. One group of such
      compounds that gained interest in recent years are the dietary anthocyanins. Data
      from their in vitro, in vivo and clinical studies are scrutinized in this
      communication to show their potential health benefit through ameliorating insulin
      resistance. Specific mechanism of action ranging from targeting specific signal
      transduction receptors/enzymes to the general antioxidant and anti-inflammatory
      mechanisms of insulin resistance are presented.

PMID- 29023433
TI  - QuickStats: Percentage* of All Visits by Patients Aged >=65 Years to Office-Based
      Physicians? Made by Patients with Hypertension,S by Sex and Metropolitan
      Statistical Area (MSA)  - National Ambulatory Medical Care Survey, United States,
      2012-2015.
AB  - During 2012-2015, patients aged >=65 years with hypertension documented in the
      medical record accounted for 54% of all office-based physician visits made by
      patients aged >=65 years, with a higher percentage of visits in non-MSAs (59%)
      than MSAs (53%). Among women, the percentage of visits was also higher in non
      MSAs than in MSAs (59% versus 53%). The difference among men was not
      statistically significant.

PMID- 29023431
TI  - HIV Care Outcomes Among Hispanics or Latinos with Diagnosed HIV Infection -
      United States, 2015.
AB  - Data from CDC's National HIV Surveillance System (NHSS)* are used to monitor
      progress toward achieving national goals set forth in the Division of HIV/AIDS
      Prevention's Strategic Plan (1) and other federal directives? for human
      immunodeficiency virus (HIV) testing, care, and treatment outcomes and HIV
      related disparities in the United States. Recent data indicate that Hispanics or
      LatinosS are disproportionately affected by HIV infection. Hispanics or Latinos
      living with diagnosed HIV infection have lower levels of care and viral
      suppression than do non-Hispanic whites but higher levels than those reported
      among blacks or African Americans (2). The annual rate of diagnosis of HIV
      infection among Hispanics or Latinos is three times that of non-Hispanic whites
      (3), and a recent study found increases in incidence of HIV infection among
      Hispanic or Latino men who have sex with men (4). Among persons with HIV
      infection diagnosed through 2013 who were alive at year-end 2014, 70.2% of
      Hispanics or Latinos received any HIV medical care compared with 76.1% of non
      Hispanic whites (2). CDC used NHSS data to describe HIV care outcomes among
      Hispanics or Latinos. Among male Hispanics or Latinos with HIV infection
      diagnosed in 2015, fewer males with infection attributed to heterosexual contact
      (34.6%) had their infection diagnosed at an early stage (stage 1 = 12.0%, stage 2
      = 22.6%) than males with infection attributed to male-to-male sexual contact
      (60.9%: stage 1 = 25.2%, stage 2 = 35.7%). The percentage of Hispanics or Latinos
      linked to care after diagnosis of HIV infection increased with increasing age;
      females aged 45-54 years with infection attributed to injection drug use (IDU)
      accounted for the lowest percentage (61.4%) of persons linked to care. Among
      Hispanics or Latinos living with HIV infection, care and viral suppression were
      lower among selected age groups of Hispanic or Latino males with HIV infection
      attributed to IDU than among males with infection attributed to male-to-male
      sexual contact and male-to-male sexual contact and IDU. Intensified efforts to
      develop and implement effective interventions and public health strategies that
      increase engagement in care and viral suppression among Hispanics or Latinos
      (3,5), particularly those who inject drugs, are needed to achieve national HIV
      prevention goals.

PMID- 29023434
TI  - Announcement: Global Handwashing Day - October 15, 2017.

PMID- 29023435
TI  - Notes from the Field: Multiple Cases of Seoul Virus Infection in a Household with
      Infected Pet Rats - Tennessee, December 2016-April 2017.

PMID- 29023436
TI  - Responsible implementation of expanded carrier screening.
AB  - This corrects the article DOI: 10.1038/ejhg.2015.271.

PMID- 29023437
TI  - 22 Years of predictive testing for Huntington's disease: the experience of the UK
      Huntington's Prediction Consortium.
AB  - This corrects the article DOI: 10.1038/ejhg.2016.36.

PMID- 29023438
TI  - The TAD-pathway for GWAS signals.

PMID- 29023439
TI  - Reconstructing the population history of the largest tribe of India: the
      Dravidian speaking Gond.
AB  - This corrects the article DOI: 10.1038/ejhg.2016.198.

PMID- 29023440
TI  - Glaucoma spectrum and age-related prevalence of individuals with FOXC1 and PITX2
      variants.
AB  - This corrects the article DOI: 10.1038/ejhg.2017.59.

PMID- 29023441
TI  - Women are underrepresented in computational biology: An analysis of the scholarly
      literature in biology, computer science and computational biology.
AB  - While women are generally underrepresented in STEM fields, there are noticeable
      differences between fields. For instance, the gender ratio in biology is more
      balanced than in computer science. We were interested in how this difference is
      reflected in the interdisciplinary field of computational/quantitative biology.
      To this end, we examined the proportion of female authors in publications from
      the PubMed and arXiv databases. There are fewer female authors on research papers
      in computational biology, as compared to biology in general. This is true across
      authorship position, year, and journal impact factor. A comparison with arXiv
      shows that quantitative biology papers have a higher ratio of female authors than
      computer science papers, placing computational biology in between its two parent
      fields in terms of gender representation. Both in biology and in computational
      biology, a female last author increases the probability of other authors on the
      paper being female, pointing to a potential role of female PIs in influencing the
      gender balance.

PMID- 29023442
TI  - Environmental perturbations lead to extensive directional shifts in RNA
      processing.
AB  - Environmental perturbations have large effects on both organismal and cellular
      traits, including gene expression, but the extent to which the environment
      affects RNA processing remains largely uncharacterized. Recent studies have
      identified a large number of genetic variants associated with variation in RNA
      processing that also have an important role in complex traits; yet we do not know
      in which contexts the different underlying isoforms are used. Here, we
      comprehensively characterized changes in RNA processing events across 89
      environments in five human cell types and identified 15,300 event shifts (FDR =
      15%) comprised of eight event types in over 4,000 genes. Many of these changes
      occur consistently in the same direction across conditions, indicative of global
      regulation by trans factors. Accordingly, we demonstrate that environmental
      modulation of splicing factor binding predicts shifts in intron retention, and
      that binding of transcription factors predicts shifts in alternative first exon
      (AFE) usage in response to specific treatments. We validated the mechanism
      hypothesized for AFE in two independent datasets. Using ATAC-seq, we found
      altered binding of 64 factors in response to selenium at sites of AFE shift,
      including ELF2 and other factors in the ETS family. We also performed AFE QTL
      mapping in 373 individuals and found an enrichment for SNPs predicted to disrupt
      binding of the ELF2 factor. Together, these results demonstrate that RNA
      processing is dramatically changed in response to environmental perturbations
      through specific mechanisms regulated by trans factors.

PMID- 29023444
TI  - Ten simple rules for writing a response to reviewers.

PMID- 29023443
TI  - Systematic, network-based characterization of therapeutic target inhibitors.
AB  - A large fraction of the proteins that are being identified as key tumor
      dependencies represent poor pharmacological targets or lack clinically-relevant
      small-molecule inhibitors. Availability of fully generalizable approaches for the
      systematic and efficient prioritization of tumor-context specific protein
      activity inhibitors would thus have significant translational value.
      Unfortunately, inhibitor effects on protein activity cannot be directly measured
      in systematic and proteome-wide fashion by conventional biochemical assays. We
      introduce OncoLead, a novel network based approach for the systematic
      prioritization of candidate inhibitors for arbitrary targets of therapeutic
      interest. In vitro and in vivo validation confirmed that OncoLead analysis can
      recapitulate known inhibitors as well as prioritize novel, context-specific
      inhibitors of difficult targets, such as MYC and STAT3. We used OncoLead to
      generate the first unbiased drug/regulator interaction map, representing
      compounds modulating the activity of cancer-relevant transcription factors, with
      potential in precision medicine.

PMID- 29023447
TI  - Network approaches and applications in biology.

PMID- 29023445
TI  - Identifying direct contacts between protein complex subunits from their
      conditional dependence in proteomics datasets.
AB  - Determining the three dimensional arrangement of proteins in a complex is highly
      beneficial for uncovering mechanistic function and interpreting genetic variation
      in coding genes comprising protein complexes. There are several methods for
      determining co-complex interactions between proteins, among them co-fractionation
      / mass spectrometry (CF-MS), but it remains difficult to identify directly
      contacting subunits within a multi-protein complex. Correlation analysis of CF-MS
      profiles shows promise in detecting protein complexes as a whole but is limited
      in its ability to infer direct physical contacts among proteins in sub-complexes.
      To identify direct protein-protein contacts within human protein complexes we
      learn a sparse conditional dependency graph from approximately 3,000 CF-MS
      experiments on human cell lines. We show substantial performance gains in
      estimating direct interactions compared to correlation analysis on a benchmark of
      large protein complexes with solved three-dimensional structures. We demonstrate
      the method's value in determining the three dimensional arrangement of proteins
      by making predictions for complexes without known structure (the exocyst and tRNA
      multi-synthetase complex) and by establishing evidence for the structural
      position of a recently discovered component of the core human EKC/KEOPS complex,
      GON7/C14ORF142, providing a more complete 3D model of the complex. Direct contact
      prediction provides easily calculable additional structural information for large
      scale protein complex mapping studies and should be broadly applicable across
      organisms as more CF-MS datasets become available.

PMID- 29023446
TI  - Towards elimination of visceral leishmaniasis in the Indian subcontinent
      Translating research to practice to public health.
AB  - BACKGROUND: The decade following the Regional Strategic Framework for Visceral
      Leishmaniasis (VL) elimination in 2005 has shown compelling progress in the
      reduction of VL burden in the Indian subcontinent. The Special Programme for
      Research and Training in Tropical Diseases (TDR), hosted by the World Health
      Organization (WHO) and other stakeholders, has coordinated and financed research
      for the development of new innovative tools and strategies to support the
      regional VL elimination initiative. This paper describes the process of the TDR's
      engagement and contribution to this initiative. METHODOLOGY/PRINCIPAL FINDINGS:
      Multiple databases were searched to identify 152 scientific papers and reports
      with WHO funding or authorship affiliation around the following 3 framework
      strategies: detection of new cases, morbidity reduction, and prevention of
      infection. TDR has played a critical role in the evaluation and subsequent use of
      the 39-aminoacid-recombinant kinesin antigen (rK39) rapid diagnostic test (RDT)
      as a confirmatory test for VL in the national program. TDR has supported the
      clinical research and development of miltefosine and single-dose liposomal
      amphotericin B as a first-line treatment against VL. TDR has engaged with in
      country researchers, national programme managers, and partners to generate
      evidence-based interventions for early detection and treatment of VL patients.
      TDR evaluated the quality, community acceptance, and cost effectiveness of indoor
      residual spraying, insecticide-treated bed nets, insecticide-impregnated durable
      wall linings, insecticidal paint, and environmental management as tools for
      integrated vector management in reducing sandfly density.
      CONCLUSIONS/SIGNIFICANCE: TDR's engagement with country policy makers,
      scientists, and clinicians in the development of effective diagnosis, treatment,
      case detection, and vector control represents an important example of TDR's
      stewardship toward the elimination of VL in the Indian subcontinent.

PMID- 29023449
TI  - Network propagation in the cytoscape cyberinfrastructure.
AB  - Network propagation is an important and widely used algorithm in systems biology,
      with applications in protein function prediction, disease gene prioritization,
      and patient stratification. However, up to this point it has required significant
      expertise to run. Here we extend the popular network analysis program Cytoscape
      to perform network propagation as an integrated function. Such integration
      greatly increases the access to network propagation by putting it in the hands of
      biologists and linking it to the many other types of network analysis and
      visualization available through Cytoscape. We demonstrate the power and utility
      of the algorithm by identifying mutations conferring resistance to Vemurafenib.

PMID- 29023448
TI  - Structural host-microbiota interaction networks.
AB  - Hundreds of different species colonize multicellular organisms making them
      "metaorganisms". A growing body of data supports the role of microbiota in health
      and in disease. Grasping the principles of host-microbiota interactions (HMIs) at
      the molecular level is important since it may provide insights into the
      mechanisms of infections. The crosstalk between the host and the microbiota may
      help resolve puzzling questions such as how a microorganism can contribute to
      both health and disease. Integrated superorganism networks that consider host and
      microbiota as a whole-may uncover their code, clarifying perhaps the most
      fundamental question: how they modulate immune surveillance. Within this
      framework, structural HMI networks can uniquely identify potential microbial
      effectors that target distinct host nodes or interfere with endogenous host
      interactions, as well as how mutations on either host or microbial proteins
      affect the interaction. Furthermore, structural HMIs can help identify master
      host cell regulator nodes and modules whose tweaking by the microbes promote
      aberrant activity. Collectively, these data can delineate pathogenic mechanisms
      and thereby help maximize beneficial therapeutics. To date, challenges in
      experimental techniques limit large-scale characterization of HMIs. Here we
      highlight an area in its infancy which we believe will increasingly engage the
      computational community: predicting interactions across kingdoms, and mapping
      these on the host cellular networks to figure out how commensal and pathogenic
      microbiota modulate the host signaling and broadly cross-species consequences.

PMID- 29023450
TI  - Incorporating networks in a probabilistic graphical model to find drivers for
      complex human diseases.
AB  - Discovering genetic mechanisms driving complex diseases is a hard problem.
      Existing methods often lack power to identify the set of responsible genes.
      Protein-protein interaction networks have been shown to boost power when
      detecting gene-disease associations. We introduce a Bayesian framework, Conflux,
      to find disease associated genes from exome sequencing data using networks as a
      prior. There are two main advantages to using networks within a probabilistic
      graphical model. First, networks are noisy and incomplete, a substantial
      impediment to gene discovery. Incorporating networks into the structure of a
      probabilistic models for gene inference has less impact on the solution than
      relying on the noisy network structure directly. Second, using a Bayesian
      framework we can keep track of the uncertainty of each gene being associated with
      the phenotype rather than returning a fixed list of genes. We first show that
      using networks clearly improves gene detection compared to individual gene
      testing. We then show consistently improved performance of Conflux compared to
      the state-of-the-art diffusion network-based method Hotnet2 and a variety of
      other network and variant aggregation methods, using randomly generated and
      literature-reported gene sets. We test Hotnet2 and Conflux on several network
      configurations to reveal biases and patterns of false positives and false
      negatives in each case. Our experiments show that our novel Bayesian framework
      Conflux incorporates many of the advantages of the current state-of-the-art
      methods, while offering more flexibility and improved power in many gene-disease
      association scenarios.

PMID- 29023451
TI  - Caring or daring? Exploring the impact of facial masculinity/femininity and
      gender category information on first impressions.
AB  - In two studies we disentangled and systematically investigated the impact of
      subtle facial cues to masculinity/femininity and gender category information on
      first impressions. Participants judged the same unambiguously male and female
      target persons-either with masculine or feminine facial features slightly
      enhanced-regarding stereotypically masculine (i.e., competence) and feminine
      (i.e., warmth) personality traits. Results of both studies showed a strong effect
      of facial masculinity/femininity: Masculine-looking persons were seen as colder
      and more competent than feminine-looking persons. This effect of facial
      masculinity/femininity was not only found for typical (i.e., masculine-looking
      men and feminine-looking women) and atypical (i.e., masculine-looking women and
      feminine-looking men) category members; it was even found to be more pronounced
      for atypical than for typical category members. This finding reveals that
      comparing atypical members to the group prototype results in pronounced effects
      of facial masculinity/femininity. These contrast effects for atypical members
      predominate assimilation effects for typical members. Intriguingly, very subtle
      facial cues to masculinity/femininity strongly guide first impressions and may
      have more impact than the gender category.

PMID- 29023452
TI  - Functional imaging of cognition in an old-old population: A case for portable
      functional near-infrared spectroscopy.
AB  - In this study, functional near-infrared spectroscopy (fNIRS) was used to record
      brain activation during cognitive testing in older individuals (88+/-6yo; N = 19)
      living in residential care communities. This population, which is often
      associated with loss of personal independence due to physical or cognitive
      decline associated with aging, is also often under-represented in neuroscience
      research because of a limited means to participate in studies which often take
      place in large urban or university centers. In this study, we demonstrate the
      feasibility and initial results using a portable 8-source by 4-detector fNIRS
      system to measure brain activity from participants within residential care
      community centers. Using fNIRS, brain signals were recorded during a series of
      computerized cognitive tests, including a Symbol Digit Coding test (SDC), Stroop
      Test (ST), and Shifting Attention Test (SAT). The SDC and SAT elicited greater
      activity in the left middle frontal region of interest. Three components of the
      ST produced increases in the right middle frontal and superior frontal, and left
      superior frontal regions. An association between advanced age and increased
      activation in the right middle frontal region was observed during the incongruent
      ST. Although none of the participants had clinical dementia based on the short
      portable mental status questionnaire, the group performance was slightly below
      age-normed values on these cognitive tests. These results demonstrate the
      capability for obtaining functional neuroimaging measures in residential
      settings, which ultimately may aid in prognosis and care related to dementia in
      older adults.

PMID- 29023453
TI  - Plant water potential improves prediction of empirical stomatal models.
AB  - Climate change is expected to lead to increases in drought frequency and
      severity, with deleterious effects on many ecosystems. Stomatal responses to
      changing environmental conditions form the backbone of all ecosystem models, but
      are based on empirical relationships and are not well-tested during drought
      conditions. Here, we use a dataset of 34 woody plant species spanning global
      forest biomes to examine the effect of leaf water potential on stomatal
      conductance and test the predictive accuracy of three major stomatal models and a
      recently proposed model. We find that current leaf-level empirical models have
      consistent biases of over-prediction of stomatal conductance during dry
      conditions, particularly at low soil water potentials. Furthermore, the recently
      proposed stomatal conductance model yields increases in predictive capability
      compared to current models, and with particular improvement during drought
      conditions. Our results reveal that including stomatal sensitivity to declining
      water potential and consequent impairment of plant water transport will improve
      predictions during drought conditions and show that many biomes contain a
      diversity of plant stomatal strategies that range from risky to conservative
      stomatal regulation during water stress. Such improvements in stomatal simulation
      are greatly needed to help unravel and predict the response of ecosystems to
      future climate extremes.

PMID- 29023454
TI  - Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by
      blocking adhesion and nutrient depletion.
AB  - Candida albicans is an inhabitant of mucosal surfaces in healthy individuals but
      also the most common cause of fungal nosocomial blood stream infections,
      associated with high morbidity and mortality. As such life-threatening infections
      often disseminate from superficial mucosal infections we aimed to study the use
      of probiotic Lactobacillus rhamnosus GG (LGG) in prevention of mucosal C.
      albicans infections. Here, we demonstrate that LGG protects oral epithelial
      tissue from damage caused by C. albicans in our in vitro model of oral
      candidiasis. Furthermore, we provide insights into the mechanisms behind this
      protection and dissect direct and indirect effects of LGG on C. albicans
      pathogenicity. C. albicans viability was not affected by LGG. Instead,
      transcriptional profiling using RNA-Seq indicated dramatic metabolic
      reprogramming of C. albicans. Additionally, LGG had a significant impact on major
      virulence attributes, including adhesion, invasion, and hyphal extension, whose
      reduction, consequently, prevented epithelial damage. This was accompanied by
      glucose depletion and repression of ergosterol synthesis, caused by LGG, but also
      due to blocked adhesion sites. Therefore, LGG protects oral epithelia against C.
      albicans infection by preventing fungal adhesion, invasion and damage, driven, at
      least in parts, by metabolic reprogramming due to nutrient limitation caused by
      LGG.

PMID- 29023455
TI  - Association between anthropometric indicators of adiposity and hypertension in a
      Brazilian population: Baependi Heart Study.
AB  - BACKGROUND: Recently, some studies have evaluated the role of adiposity measures
      in the prediction of hypertension risk, but the results are conflicting. Thus,
      the aim of this study was to compare which of the four indicators of adiposity
      (waist circumference-WC, body mass index-BMI, body adiposity index-BAI, and
      visceral adiposity index-VAI) were better associated with hypertension in a
      Brazilian population. METHODS AND FINDINGS: For this study, were selected 1627
      individuals (both genders, and aged over 18 years) resident in the municipality
      of Baependi, a city located in the Southeast of Brazil. WC, BMI, BAI and VAI were
      determined according to a standard protocol. Hypertension was defined as mean
      systolic blood pressure >= 140 mmHg and/or diastolic blood pressure >= 90 mmHg,
      and/or antihypertensive drug use. The indicators of adiposity WC, BMI, BAI, and
      VAI were higher in hypertensive when compared to non-hypertensive individuals. In
      addition, WC and BMI were most strongly associated with hypertension in men and
      women, respectively. The area under the curve (AUC) of WC was significantly
      higher than VAI in men. In women, both AUC of BMI and WC showed higher
      discriminatory power to predict hypertension than BAI and VAI. CONCLUSIONS: The
      indicators of adiposity WC and BMI were better associated with hypertension than
      BAI and VAI, in both genders, and it could be a useful tools for the screening of
      hypertensive patients.

PMID- 29023456
TI  - Gait parameters are differently affected by concurrent smartphone-based
      activities with scaled levels of cognitive effort.
AB  - The widespread and pervasive use of smartphones for sending messages, calling,
      and entertainment purposes, mainly among young adults, is often accompanied by
      the concurrent execution of other tasks. Recent studies have analyzed how
      texting, reading or calling while walking-in some specific conditions-might
      significantly influence gait parameters. The aim of this study is to examine the
      effect of different smartphone activities on walking, evaluating the variations
      of several gait parameters. 10 young healthy students (all smartphone proficient
      users) were instructed to text chat (with two different levels of cognitive
      load), call, surf on a social network or play with a math game while walking in a
      real-life outdoor setting. Each of these activities is characterized by a
      different cognitive load. Using an inertial measurement unit on the lower trunk,
      spatio-temporal gait parameters, together with regularity, symmetry and
      smoothness parameters, were extracted and grouped for comparison among normal
      walking and different dual task demands. An overall significant effect of task
      type on the aforementioned parameters group was observed. The alterations in gait
      parameters vary as a function of cognitive effort. In particular, stride
      frequency, step length and gait speed show a decrement, while step time increases
      as a function of cognitive effort. Smoothness, regularity and symmetry parameters
      are significantly altered for specific dual task conditions, mainly along the
      mediolateral direction. These results may lead to a better understanding of the
      possible risks related to walking and concurrent smartphone use.

PMID- 29023457
TI  - The DMT1 IVS4+44C>A polymorphism and the risk of iron deficiency anemia in
      children with celiac disease.
AB  - BACKGROUND: Iron deficiency anemia in celiac disease is related to impaired
      duodenal mucosal uptake, due to villous atrophy. Iron enters the enterocytes
      through an apical divalent metal transporter, DMT1. Different DMT1 transcripts
      have been identified, depending on the presence of an iron-responsive element
      that allows DMT1 up-regulation during iron starvation. An intronic DMT1
      polymorphism, IVS4+44C>A, has been associated with metal toxicity, and the CC
      carriers show high iron levels. AIMS: This study investigates the association
      between DMT1 IVS4+44C>A and anemia in a cohort of 387 Italian celiac children,
      and the functional role of the polymorphism. METHODS AND RESULTS: By association
      analysis, we found that DMT1 IVS4+44-AA genotype confers a four-fold risk of
      developing anemia, despite of atrophy degree. By analysis of mRNA from
      gastroesophageal biopsies, we found that total DMT1 is significantly upregulated
      in presence of mild, but not severe, atrophy, independently from IVS4+44C>A
      variant, and in normal but not in atrophic CC-biopsies. Moreover, we found that A
      allele is associated to preferential expression of the DMT1 transcripts lacking
      the iron-responsive element, thus limiting the DMT1 overexpression that normally
      occurs to respond to iron starvation. DISCUSSION: Possibly, the IVS4+44-AA
      related dysregulation of the iron-induced changes in DMT1 expression is not able
      to impair iron absorption in physiological condition. However, if exacerbated by
      the concomitant massive loss of functional absorbing tissue paralleling worsened
      stages of villus atrophy, it might be ineffective in counteracting iron
      deficiency, despite of DMT1 overexpression. CONCLUSION: We suggest, for the first
      time, that celiac disease may unmask the contribution of the DMT1 IVS4+44C>A
      polymorphism to the risk of anemia.

PMID- 29023458
TI  - Emergence of encounter networks due to human mobility.
AB  - There is a burst of work on human mobility and encounter networks. However, the
      connection between these two important fields just begun recently. It is clear
      that both are closely related: Mobility generates encounters, and these
      encounters might give rise to contagion phenomena or even friendship. We model a
      set of random walkers that visit locations in space following a strategy akin to
      Levy flights. We measure the encounters in space and time and establish a link
      between walkers after they coincide several times. This generates a temporal
      network that is characterized by global quantities. We compare this dynamics with
      real data for two cities: New York City and Tokyo. We use data from the location
      based social network Foursquare and obtain the emergent temporal encounter
      network, for these two cities, that we compare with our model. We found long
      range (Levy-like) distributions for traveled distances and time intervals that
      characterize the emergent social network due to human mobility. Studying this
      connection is important for several fields like epidemics, social influence,
      voting, contagion models, behavioral adoption and diffusion of ideas.

PMID- 29023459
TI  - Chlorophyte aspartyl aminopeptidases: Ancient origins, expanded families, new
      locations, and secondary functions.
AB  - M18 aspartyl aminopeptidases (DAPs) are well characterized in microbes and
      animals with likely functions in peptide processing and vesicle trafficking. In
      contrast, there is a dearth of knowledge on plant aminopeptidases with a
      preference for proteins and peptides with N-terminal acidic residues. During
      evolution of the Plantae, there was an expansion and diversification of the M18
      DAPs. After divergence of the ancestral green algae from red and glaucophyte
      algae, a duplication yielded the DAP1 and DAP2 lineages. Subsequently DAP1 genes
      were lost in chlorophyte algae. A duplication of DAP2-related genes occurred
      early in green plant evolution. DAP2 genes were retained in land plants and
      picoeukaryotic algae and lost in green algae. In contrast, DAP2-like genes
      persisted in picoeukaryotic and green algae, while this lineage was lost in land
      plants. Consistent with this evolutionary path, Arabidopsis thaliana has two DAP
      gene lineages (AtDAP1 and AtDAP2). Similar to animal and yeast DAPs, AtDAP1 is
      localized to the cytosol or vacuole; while AtDAP2 harbors an N-terminal transit
      peptide and is chloroplast localized. His6-DAP1 and His6-DAP2 expressed in
      Escherichia coli were enzymatically active and dodecameric with masses exceeding
      600 kDa. His6-DAP1 and His6-DAP2 preferentially hydrolyzed Asp-p-nitroanilide and
      Glu-p-nitroanilide. AtDAPs are highly conserved metallopeptidases activated by
      MnCl2 and inhibited by ZnCl2 and divalent ion chelators. The protease inhibitor
      PMSF inhibited and DTT stimulated both His6-DAP1 and His6-DAP2 activities
      suggesting a role for thiols in the AtDAP catalytic mechanism. The enzymes had
      distinct pH and temperature optima, as well as distinct kinetic parameters. Both
      enzymes had high catalytic efficiencies (kcat/Km) exceeding 1.0 x 107 M-1 sec-1.
      Using established molecular chaperone assays, AtDAP1 and AtDAP2 prevented thermal
      denaturation. AtDAP1 also prevented protein aggregation and promoted protein
      refolding. Collectively, these data indicate that plant DAPs have a complex
      evolutionary history and have evolved new biochemical features that may enable
      their role in vivo.

PMID- 29023460
TI  - The association between photoreceptor layer thickness measured by optical
      coherence tomography and visual sensitivity in glaucomatous eyes.
AB  - PURPOSE: To assess the thickness of the photoreceptor layer in the macular region
      in glaucomatous eyes. METHOD: Humphrey 10-2 visual field (VF) testing was carried
      out and mean threshold (mTH) was calculated in 118 eyes from 118 patients with
      open angle glaucoma. Macular optical coherence tomography (OCT) measurements (RS
      3000, Nidek Co.ltd., Aichi, Japan) were also carried out in all eyes. Thickness
      measurements were recorded in the outer segment and retinal pigment epithelium
      (OS+RPE), the nerve fiber layer (NFL), the ganglion cell layer and inner
      plexiform layer (GCL+IPL), the inner nuclear layer and outer plexiform layer
      (INL+OPL) and the outer nuclear layer and inner segment (ONL+IS). The
      relationship between mTH and the thickness of these five different layers was
      investigated. Additionally, the influence of OS+RPE on mTH was investigated using
      partial correlation eliminating the effect of other variables of NFL, GCL+IPL,
      INL+OPL, ONL+IS, age, gender and axial length. RESULTS: The thickness of the
      OS+RPE layer was significantly decreased with the decrease of mTH (coefficient =
      0.63 p <0.001). Partial correlation analysis suggested OS+RPE thickness is
      significantly (coefficient = 0.31, p <0.001) related to mTH, independent from
      NFL, GCL+IPL, INL+OPL, ONL+IS, age, gender and axial length. CONCLUSIONS: The
      thickness of the RPE+OS layer appears to be related to visual sensitivity in
      glaucoma.

PMID- 29023461
TI  - The development of fears of compassion scale Japanese version.
AB  - OBJECTIVES: Cultivation of compassion is a useful way to treat mental problems,
      but some individuals show resistance. Fears of compassion can be an obstacle for
      clinicians when providing psychotherapy, and for clients when engaging in
      interpersonal relationships. Despite its importance, a Japanese version of fears
      of compassion scales (for others, from others, and for self) has not yet been
      developed. This study developed a Japanese version of the Fears of Compassion
      Scales and tested its reliability and validity. DESIGN: This study used a cross
      sectional design, and a self-report procedure for collecting data. METHODS: A
      total of 485 students (121 males and 364 females) answered self-report
      questionnaires, including the draft Fears of Compassion Scales-Japanese version.
      RESULTS: There were distinctive factor structures for fear of compassion from
      others, and for self. The fear of compassion from others scale consisted of
      concern about compassion from others and avoidance of compassion from others. All
      scales had good internal consistency, test-retest reliability, face validity, and
      construct validity. Discrimination and difficulty were also calculated.
      CONCLUSIONS: These results indicate that the Fears of Compassion Scales-Japanese
      version is a well-constructed and useful measure to assess fears of compassion
      and the existence of cultural differences in fears of compassion.

PMID- 29023462
TI  - The sound of trustworthiness: Acoustic-based modulation of perceived voice
      personality.
AB  - When we hear a new voice we automatically form a "first impression" of the voice
      owner's personality; a single word is sufficient to yield ratings highly
      consistent across listeners. Past studies have shown correlations between
      personality ratings and acoustical parameters of voice, suggesting a potential
      acoustical basis for voice personality impressions, but its nature and extent
      remain unclear. Here we used data-driven voice computational modelling to
      investigate the link between acoustics and perceived trustworthiness in the
      single word "hello". Two prototypical voice stimuli were generated based on the
      acoustical features of voices rated low or high in perceived trustworthiness,
      respectively, as well as a continuum of stimuli inter- and extrapolated between
      these two prototypes. Five hundred listeners provided trustworthiness ratings on
      the stimuli via an online interface. We observed an extremely tight relationship
      between trustworthiness ratings and position along the trustworthiness continuum
      (r = 0.99). Not only were trustworthiness ratings higher for the high- than the
      low-prototypes, but the difference could be modulated quasi-linearly by reducing
      or exaggerating the acoustical difference between the prototypes, resulting in a
      strong caricaturing effect. The f0 trajectory, or intonation, appeared a
      parameter of particular relevance: hellos rated high in trustworthiness were
      characterized by a high starting f0 then a marked decrease at mid-utterance to
      finish on a strong rise. These results demonstrate a strong acoustical basis for
      voice personality impressions, opening the door to multiple potential
      applications.

PMID- 29023464
TI  - Role of p16 testing in cervical cancer screening among HIV-infected women.
AB  - BACKGROUND: p16 immunohistochemistry is used to evaluate for HPV-associated
      cervical intraepithelial neoplasia. The diagnostic performance of p16 in HIV
      infection is unclear. METHODS: Between June-December 2009, HIV-infected women
      underwent Papanicolaou (Pap) smear, human papillomavirus (HPV) testing, visual
      inspection with acetic acid (VIA), and colposcopy-directed biopsy as the disease
      gold standard at a HIV clinic in Kenya. Pap smears were evaluated for p16
      expression. Sensitivity, specificity, positive predictive value (PPV), and area
      under the receiver operating characteristic curve (AUC) of p16 to detect CIN2/3
      on histology and the impact of immunosuppression and ART was assessed. RESULTS:
      Of 331 cervical samples with p16 expression, p16 sensitivity and specificity to
      detect CIN2/3 was 54.1% and 72.4% respectively, which was lower than Pap and HPV
      in sensitivity, but higher in specificity than Pap, HPV, and VIA. Combining tests
      and p16 reduced sensitivity and increased specificity of Pap from 90.5% to 48.7%
      and 51.4% to 81.7%; of VIA from 59.5% to 37.8% and 67.6% to 89.9%; and of HPV
      from 82.4% to 50.0% and 55.3% to 84.8%. Combination p16 increased the PPV of Pap
      from 34.9% to 43.4%; of HPV from 34.7% to 48.7%; and VIA from 34.9% to 51.9%.
      Adjunctive p16 did not change AUC (P>0.05). P16 performance was not altered by
      immunosuppression or ART use. Combining p16 with HPV and VIA reduced the
      variation in HPV and VIA performance associated with CD4 and ART. CONCLUSION: As
      an adjunctive test in HIV-infected women, p16 immunohistochemistry increased
      specificity and PPV of HPV and VIA for CIN2/3, and was not altered in performance
      by immunosuppression, ART, or age.

PMID- 29023465
TI  - In vitro effects of Apixaban on 5 different cancer cell lines.
AB  - BACKGROUND: Cancer is associated with hypercoagulability. However, several data
      suggest that anticoagulant drugs may have an effect on tumor development and
      progression mediated by both coagulation dependent processes and non-coagulation
      dependent processes. Therefore, we investigated the in vitro effects of Apixaban
      on cell proliferation, mortality, cell migration, gene expression and matrix
      metalloproteinase in 5 different cancer cell lines. METHODS: The following cancer
      cell lines, and 2 normal fibroblast cultures (lung and dermal fibroblasts), were
      studied: OVCAR3 (ovarian cancer), MDA MB 231 (breast cancer), CaCO-2 (colon
      cancer), LNCaP (prostate cancer) and U937 (histiocytic lymphoma). Proliferation
      and cell mortality were assessed in control cells and Apixaban treated cultures
      (dose from 0.1 to 5 MUg/ml, 0 to 96-h). Necrosis/Apoptosis (fluorescence
      microscopy), cell migration (24-h after scratch test), matrix metalloproteinase
      (MMP) activity and mRNA expression (RT PCR) of p16, p21, p53 and HAS were also
      assessed. RESULTS: High-dose (5 MUg/ml) Apixaban incubation was associated with a
      significantly reduced proliferation in 3 cancer cell lines (OVCAR3, CaCO-2 and
      LNCaP) and with increased cancer cell mortality in all, except LNCaP, cancer
      lines. Apoptosis seems to account for the increased mortality. The migration
      capacity seems to be impaired after high-dose Apixaban incubation in OVCAR3 and
      CaCO-2 cells. Data on mRNA expression suggest a consistent increase in tumor
      suppression gene p16 in all cell lines. CONCLUSIONS: Our data suggest that high
      dose Apixaban may be able to interfere with cancer cell in vitro, reducing
      proliferation and increasing cancer cell mortality through apoptosis in several
      cancer cell lines.

PMID- 29023463
TI  - Learning to tie the knot: The acquisition of functional object representations by
      physical and observational experience.
AB  - Here we examined neural substrates for physically and observationally learning to
      construct novel objects, and characterized brain regions associated with each
      kind of learning using fMRI. Each participant was assigned a training partner,
      and for five consecutive days practiced tying one group of knots ("tied"
      condition) or watched their partner tie different knots ("watched" condition)
      while a third set of knots remained untrained. Functional MRI was obtained prior
      to and immediately following the week of training while participants performed a
      visual knot-matching task. After training, a portion of left superior parietal
      lobule demonstrated a training by scan session interaction. This means this
      parietal region responded selectively to knots that participants had physically
      learned to tie in the post-training scan session but not the pre-training scan
      session. A conjunction analysis on the post-training scan data showed right
      intraparietal sulcus and right dorsal premotor cortex to respond when viewing
      images of knots from the tied and watched conditions compared to knots that were
      untrained during the post-training scan session. This suggests that these brain
      areas track both physical and observational learning. Together, the data provide
      preliminary evidence of engagement of brain regions associated with hand-object
      interactions when viewing objects associated with physical experience, and with
      observational experience without concurrent physical practice.

PMID- 29023466
TI  - Training discrimination diminishes maladaptive avoidance of innocuous stimuli in
      a fear conditioning paradigm.
AB  - Anxiety disorders are the most common mental disorder worldwide. Although anxiety
      disorders differ in the nature of feared objects or situations, they share a
      common mechanism by which fear generalizes to related but innocuous objects,
      eliciting avoidance of objects and situations that pose no objective risk. This
      overgeneralization appears to be a crucial mechanism in the persistence of
      anxiety psychopathology. In this study we test whether an intervention that
      promotes discrimination learning reduces generalization of fear, in particular,
      harm expectancy and avoidance compared to an irrelevant (control) training.
      Healthy participants (N = 80) were randomly allocated to a training condition.
      Using a fear conditioning paradigm, participants first learned visual danger and
      safety signals (set 1). Baseline level of stimulus generalization was tested with
      ambiguous stimuli on a spectrum between the danger and safety signals. There were
      no differences between the training groups. Participants then received the
      stimulus discrimination training or a control training. After training,
      participants learned a new set of danger and safety signals (set 2), and the
      level of harm expectancy generalization and behavioural avoidance of ambiguous
      stimuli was tested. Although the training groups did not differ in fear
      generalization on a cognitive level (harm expectancy), the results showed a
      different pattern of avoidance of ambiguous stimuli, with the discrimination
      training group showing less avoidance of stimuli that resembled the safety
      signals. These results support the potential of interventions that promote
      discrimination learning in the treatment of anxiety disorders.

PMID- 29023467
TI  - Dietary lactoferrin supplementation to gilts during gestation and lactation
      improves pig production and immunity.
AB  - Lactoferrin (LF), a sialylated iron-binding glycoprotein, performs multiple
      beneficial functions including modulating immunity and improves neurodevelopment,
      health and growth performance. Maternal LF intervention for gilts (first parity
      sows) on the performance of gilts and their offspring remains unknown. In the
      current study gilts were fed with a commercial pig feed supplemented with 1g LF
      /day (treatment group) or 1g milk casein/day (control group) from day 1 post
      mating throughout pregnancy and lactation for about 135 days. The milk production
      and body weight gain was monitored. The immunoglobulin concentrations in the
      serum of gilts and piglets were measured using ELISA. Our study showed that
      maternal LF supplementation to the gilt (1) significantly increased milk
      production at different time points (day 1, 3, 7 and 19) of lactation compared to
      the control (p<0.001); (2) significantly increased body weight gain of their
      piglets during the first 19 days of life compared to the control group (p<0.05);
      (3) tended to increase pregnancy rate, litter size and birth weight, number of
      piglets born alive, and decrease the number of dead and intrauterine growth
      restriction (IUGR) piglets; (4) significantly increased the concentration of
      serum IgA in gilt and serum sIgA in piglet (p<0.05). In summary, maternal Lf
      intervention in gilts can improve milk production, pig production and serum IgA
      and sIgA levels, and therefore plays a key role in shaping the performance of
      their progeny.

PMID- 29023468
TI  - The effect of allometric scaling in coral thermal microenvironments.
AB  - A long-standing interest in marine science is in the degree to which
      environmental conditions of flow and irradiance, combined with optical, thermal
      and morphological characteristics of individual coral colonies, affects their
      sensitivity of thermal microenvironments and susceptibility to stress-induced
      bleaching within and/or among colonies. The physiological processes in
      Scleractinian corals tend to scale allometrically as a result of physical and
      geometric constraints on body size and shape. There is a direct relationship
      between scaling to thermal stress, thus, the relationship between allometric
      scaling and rates of heating and cooling in coral microenvironments is a subject
      of great interest. The primary aim of this study was to develop an approximation
      that predicts coral thermal microenvironments as a function of colony morphology
      (shape and size), light or irradiance, and flow velocity or regime. To do so, we
      provided intuitive interpretation of their energy budgets for both massive and
      branching colonies, and then quantified the heat-size exponent (b*) and
      allometric constant (m) using logarithmic linear regression. The data
      demonstrated a positive relationship between thermal rates and changes in
      irradiance, A/V ratio, and flow, with an interaction where turbulent regime had
      less influence on overall stress which may serve to ameliorate the effects of
      temperature rise compared to the laminar regime. These findings indicated that
      smaller corals have disproportionately higher stress, however they can reach
      thermal equilibrium quicker. Moreover, excellent agreements between the predicted
      and simulated microscale temperature values with no significant bias were
      observed for both the massive and branching colonies, indicating that the
      numerical approximation should be within the accuracy with which they could be
      measured. This study may assist in estimating the coral microscale temperature
      under known conditions of water flow and irradiance, in particular when examining
      the intra- and inter-colony variability found during periods of bleaching
      conditions.

PMID- 29023469
TI  - The common oncogenomic program of NOTCH1 and NOTCH3 signaling in T-cell acute
      lymphoblastic leukemia.
AB  - Notch is a major oncogenic driver in T cell acute lymphoblastic leukemia (T-ALL),
      in part because it binds to an enhancer that increases expression of MYC. Here,
      we exploit the capacity of activated NOTCH1 and NOTCH3 to induce T-ALL, despite
      substantial divergence in their intracellular regions, as a means to elucidate a
      broad, common Notch-dependent oncogenomic program through systematic comparison
      of the transcriptomes and Notch-bound genomic regulatory elements of NOTCH1- and
      NOTCH3-dependent T-ALL cells. ChIP-seq studies show a high concordance of
      functional NOTCH1 and NOTCH3 genomic binding sites that are enriched in binding
      motifs for RBPJ, the transcription factor that recruits activated Notch to DNA.
      The interchangeability of NOTCH1 and NOTCH3 was confirmed by rescue of NOTCH1
      dependent T-ALL cells with activated NOTCH3 and vice versa. Despite remarkable
      overall similarity, there are nuanced differences in chromatin landscapes near
      critical common Notch target genes, most notably at a Notch-dependent enhancer
      that regulates MYC, which correlates with responsiveness to Notch pathway
      inhibitors. Overall, a common oncogenomic program driven by binding of either
      Notch is sufficient to maintain T-ALL cell growth, whereas cell-context specific
      differences appear to influence the response of T-ALL cells to Notch inhibition.

PMID- 29023470
TI  - Vicus: Exploiting local structures to improve network-based analysis of
      biological data.
AB  - Biological networks entail important topological features and patterns critical
      to understanding interactions within complicated biological systems. Despite a
      great progress in understanding their structure, much more can be done to improve
      our inference and network analysis. Spectral methods play a key role in many
      network-based applications. Fundamental to spectral methods is the Laplacian, a
      matrix that captures the global structure of the network. Unfortunately, the
      Laplacian does not take into account intricacies of the network's local structure
      and is sensitive to noise in the network. These two properties are fundamental to
      biological networks and cannot be ignored. We propose an alternative matrix
      Vicus. The Vicus matrix captures the local neighborhood structure of the network
      and thus is more effective at modeling biological interactions. We demonstrate
      the advantages of Vicus in the context of spectral methods by extensive empirical
      benchmarking on tasks such as single cell dimensionality reduction, protein
      module discovery and ranking genes for cancer subtyping. Our experiments show
      that using Vicus, spectral methods result in more accurate and robust performance
      in all of these tasks.

PMID- 29023471
TI  - Combinatorial action of Grainyhead, Extradenticle and Notch in regulating Hox
      mediated apoptosis in Drosophila larval CNS.
AB  - Hox mediated neuroblast apoptosis is a prevalent way to pattern larval central
      nervous system (CNS) by different Hox genes, but the mechanism of this apoptosis
      is not understood. Our studies with Abdominal-A (Abd-A) mediated larval
      neuroblast (pNB) apoptosis suggests that AbdA, its cofactor Extradenticle (Exd),
      a helix-loop-helix transcription factor Grainyhead (Grh), and Notch signaling
      transcriptionally contribute to expression of RHG family of apoptotic genes. We
      find that Grh, AbdA, and Exd function together at multiple motifs on the
      apoptotic enhancer. In vivo mutagenesis of these motifs suggest that they are
      important for the maintenance of the activity of the enhancer rather than its
      initiation. We also find that Exd function is independent of its known partner
      homothorax in this apoptosis. We extend some of our findings to Deformed
      expressing region of sub-esophageal ganglia where pNBs undergo a similar Hox
      dependent apoptosis. We propose a mechanism where common players like Exd-Grh
      Notch work with different Hox genes through region specific enhancers to pattern
      respective segments of larval central nervous system.

PMID- 29023472
TI  - Geographic variations of the bird-borne structural risk of West Nile virus
      circulation in Europe.
AB  - The structural risk of West Nile Disease results from the usual functioning of
      the socio-ecological system, which may favour the introduction of the pathogen,
      its circulation and the occurrence of disease cases. Its geographic variations
      result from the local interactions between three components: (i) reservoir hosts,
      (ii) vectors, both characterized by their diversity, abundance and competence,
      (iii) and the socio-economic context that impacts the exposure of human to
      infectious bites. We developed a model of bird-borne structural risk of West Nile
      Virus (WNV) circulation in Europe, and analysed the association between the
      geographic variations of this risk and the occurrence of WND human cases between
      2002 and 2014. A meta-analysis of WNV serosurveys conducted in wild bird
      populations was performed to elaborate a model of WNV seropositivity in European
      bird species, considered a proxy for bird exposure to WNV. Several eco
      ethological traits of bird species were linked to seropositivity and the
      statistical model adequately fitted species-specific seropositivity data (area
      under the ROC curve: 0.85). Combined with species distribution maps, this model
      allowed deriving geographic variations of the bird-borne structural risk of WNV
      circulation. The association between this risk, and the occurrence of WND human
      cases across the European Union was assessed. Geographic risk variations of bird
      borne structural risk allowed predicting WND case occurrence in administrative
      districts of the EU with a sensitivity of 86% (95% CI: 0.79-0.92), and a
      specificity of 68% (95% CI: 0.66-0.71). Disentangling structural and conjectural
      health risks is important for public health managers as risk mitigation
      procedures differ according to risk type. The results obtained show promise for
      the prevention of WND in Europe. Combined with analyses of vector-borne
      structural risk, they should allow designing efficient and targeted prevention
      measures.

PMID- 29023473
TI  - Comparison of bioavailability and antiplatelet action of ticagrelor in patients
      with ST-elevation myocardial infarction and non-ST-elevation myocardial
      infarction: A prospective, observational, single-centre study.
AB  - BACKGROUND: Data from available studies suggest that the presence of ST-elevation
      myocardial infarction (STEMI) may be associated with delayed and attenuated
      ticagrelor bioavailability and effect compared with non-ST-elevation myocardial
      infarction (NSTEMI). METHODS: In a single-center, prospective, observational
      trial 73 patients with myocardial infarction (STEMI n = 49, NSTEMI n = 24)
      underwent a pharmacokinetic and pharmacodynamic assessment after a 180 mg
      ticagrelor loading dose (LD). Ticagrelor and its active metabolite (AR-C124910XX)
      plasma concentrations were determined with liquid chromatography tandem mass
      spectrometry, and their antiplatelet effect was measured with the VASP assay and
      multiple electrode aggregometry. RESULTS: During the first six hours after
      ticagrelor LD, STEMI patients had 38% and 34% lower plasma concentration of
      ticagrelor and AR-C124910XX, respectively, than NSTEMI (ticagrelor AUC(0-6): 2491
      [344-5587] vs. 3991 [1406-9284] ng*h/mL; p = 0.038; AR-C124910XX AUC(0-6): 473 [0
      924] vs. 712 [346-1616] ng*h/mL; p = 0.027). STEMI patients also required more
      time to achieve maximal concentration of ticagrelor (tmax: 4.0 [3.0-12.0] vs. 2.5
      [2.0-6.0] h; p = 0.012). Impaired bioavailability of ticagrelor and AR-C124910XX
      seen in STEMI subjects was associated with diminished platelet inhibition in this
      group, which was most pronounced during the initial hours of treatment.
      CONCLUSIONS: Plasma concentrations of ticagrelor and AR-C124910XX during the
      first hours after ticagrelor LD were one third lower in STEMI than in NSTEMI
      patients. This reduced and delayed ticagrelor bioavailability was associated with
      weaker antiplatelet effect in STEMI. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT02602444 (November 09, 2015).

PMID- 29023474
TI  - HIV-1 transmission networks in high risk fishing communities on the shores of
      Lake Victoria in Uganda: A phylogenetic and epidemiological approach.
AB  - BACKGROUND: Fishing communities around Lake Victoria in sub-Saharan Africa have
      been characterised as a population at high risk of HIV-infection. METHODS: Using
      data from a cohort of HIV-positive individuals aged 13-49 years, enrolled from 5
      fishing communities on Lake Victoria between 2009-2011, we sought to identify
      factors contributing to the epidemic and to understand the underlying structure
      of HIV transmission networks. Clinical and socio-demographic data were combined
      with HIV-1 phylogenetic analyses. HIV-1 gag-p24 and env-gp-41 sub-genomic
      fragments were amplified and sequenced from 283 HIV-1-infected participants.
      Phylogenetic clusters with >=2 highly related sequences were defined as
      transmission clusters. Logistic regression models were used to determine factors
      associated with clustering. RESULTS: Altogether, 24% (n = 67/283) of HIV positive
      individuals with sequences fell within 34 phylogenetically distinct clusters in
      at least one gene region (either gag or env). Of these, 83% occurred either
      within households or within community; 8/34 (24%) occurred within household
      partnerships, and 20/34 (59%) within community. 7/12 couples (58%) within
      households clustered together. Individuals in clusters with potential recent
      transmission (11/34) were more likely to be younger 71% (15/21) versus 46%
      (21/46) in un-clustered individuals and had recently become resident in the
      community 67% (14/21) vs 48% (22/46). Four of 11 (36%) potential transmission
      clusters included incident-incident transmissions. Independently, clustering was
      less likely in HIV subtype D (adjusted Odds Ratio, aOR = 0.51 [95% CI 0.26-1.00])
      than A and more likely in those living with an HIV-infected individual in the
      household (aOR = 6.30 [95% CI 3.40-11.68]). CONCLUSIONS: A large proportion of
      HIV sexual transmissions occur within house-holds and within communities even in
      this key mobile population. The findings suggest localized HIV transmissions and
      hence a potential benefit for the test and treat approach even at a community
      level, coupled with intensified HIV counselling to identify early infections.

PMID- 29023475
TI  - De novo transcriptome sequencing of Isaria cateniannulata and comparative
      analysis of gene expression in response to heat and cold stresses.
AB  - Isaria cateniannulata is a very important and virulent entomopathogenic fungus
      that infects many insect pest species. Although I. cateniannulata is commonly
      exposed to extreme environmental temperature conditions, little is known about
      its molecular response mechanism to temperature stress. Here, we sequenced and de
      novo assembled the transcriptome of I. cateniannulata in response to high and low
      temperature stresses using Illumina RNA-Seq technology. Our assembly encompassed
      17,514 unigenes (mean length = 1,197 bp), in which 11,445 unigenes (65.34%)
      showed significant similarities to known sequences in NCBI non-redundant protein
      sequences (Nr) database. Using digital gene expression analysis, 4,483
      differentially expressed genes (DEGs) were identified after heat treatment,
      including 2,905 up-regulated genes and 1,578 down-regulated genes. Under cold
      stress, 1,927 DEGs were identified, including 1,245 up-regulated genes and 682
      down-regulated genes. The expression patterns of 18 randomly selected candidate
      DEGs resulting from quantitative real-time PCR (qRT-PCR) were consistent with
      their transcriptome analysis results. Although DEGs were involved in many
      pathways, we focused on the genes that were involved in endocytosis: In heat
      stress, the pathway of clathrin-dependent endocytosis (CDE) was active; however
      at low temperature stresses, the pathway of clathrin-independent endocytosis
      (CIE) was active. Besides, four categories of DEGs acting as temperature sensors
      were observed, including cell-wall-major-components-metabolism-related (CWMCMR)
      genes, heat shock protein (Hsp) genes, intracellular-compatible-solutes
      metabolism-related (ICSMR) genes and glutathione S-transferase (GST). These
      results enhance our understanding of the molecular mechanisms of I.
      cateniannulata in response to temperature stresses and provide a valuable
      resource for the future investigations.

PMID- 29023476
TI  - Genetic and ecological insights into glacial refugia of walnut (Juglans regia
      L.).
AB  - The distribution and survival of trees during the last glacial maximum (LGM) has
      been of interest to paleoecologists, biogeographers, and geneticists. Ecological
      niche models that associate species occurrence and abundance with climatic
      variables are widely used to gain ecological and evolutionary insights and to
      predict species distributions over space and time. The present study deals with
      the glacial history of walnut to address questions related to past distributions
      through genetic analysis and ecological modeling of the present, LGM and Last
      Interglacial (LIG) periods. A maximum entropy method was used to project the
      current walnut distribution model on to the LGM (21-18 kyr BP) and LIG (130-116
      kyr BP) climatic conditions. Model tuning identified the walnut data set filtered
      at 10 km spatial resolution as the best for modeling the current distribution and
      to hindcast past (LGM and LIG) distributions of walnut. The current distribution
      model predicted southern Caucasus, parts of West and Central Asia extending into
      South Asia encompassing northern Afghanistan, Pakistan, northwestern Himalayan
      region, and southwestern Tibet, as the favorable climatic niche matching the
      modern distribution of walnut. The hindcast of distributions suggested the
      occurrence of walnut during LGM was somewhat limited to southern latitudes from
      southern Caucasus, Central and South Asian regions extending into southwestern
      Tibet, northeastern India, Himalayan region of Sikkim and Bhutan, and
      southeastern China. Both CCSM and MIROC projections overlapped, except that MIROC
      projected a significant presence of walnut in the Balkan Peninsula during the
      LGM. In contrast, genetic analysis of the current walnut distribution suggested a
      much narrower area in northern Pakistan and the surrounding areas of Afghanistan,
      northwestern India, and southern Tajikistan as a plausible hotspot of diversity
      where walnut may have survived glaciations. Overall, the findings suggest that
      walnut perhaps survived the last glaciations in several refugia across a wide
      geographic area between 30 degrees  and 45 degrees  North latitude. However,
      humans probably played a significant role in the recent history and modern
      distribution of walnut.

PMID- 29023477
TI  - Possible cases of leprosy from the Late Copper Age (3780-3650 cal BC) in Hungary.
AB  - At the Abony-Turjanyos dulo site, located in Central Hungary, a rescue excavation
      was carried out. More than 400 features were excavated and dated to the
      Protoboleraz horizon, at the beginning of the Late Copper Age in the Carpathian
      Basin, between 3780-3650 cal BC. Besides the domestic and economic units, there
      were two special areas, with nine-nine pits that differed from the other
      archaeological features of the site. In the northern pit group seven pits
      contained human remains belonging to 48 individuals. Some of them were buried
      carefully, while others were thrown into the pits. The aim of this study is to
      present the results of the paleopathological and molecular analysis of human
      remains from this Late Copper Age site. The ratio of neonates to adults was high,
      33.3%. Examination of the skeletons revealed a large number of pathological
      cases, enabling reconstruction of the health profile of the buried individuals.
      Based on the appearance and frequency of healed ante- and peri mortem trauma,
      inter-personal (intra-group) violence was characteristic in the Abony Late Copper
      Age population. However other traces of paleopathology were observed on the bones
      that appear not to have been caused by warfare or inter-group violence. The
      remains of one individual demonstrated a rare set of bone lesions that indicate
      the possible presence of leprosy (Hansen's disease). The most characteristic
      lesions occurred on the bones of the face, including erosion of the nasal
      aperture, atrophy of the anterior nasal spine, inflammation of the nasal bone and
      porosity on both the maxilla and the bones of the lower legs. In a further four
      cases, leprosy infection is suspected but other infections cannot be excluded.
      The morphologically diagnosed possible leprosy case significantly modifies our
      knowledge about the timescale and geographic spread of this specific infectious
      disease. However, it is not possible to determine the potential connections
      between the cases of possible leprosy and the special burial circumstances.

PMID- 29023478
TI  - Regeneration of glycocalyx by heparan sulfate and sphingosine 1-phosphate
      restores inter-endothelial communication.
AB  - Vasculoprotective endothelium glycocalyx (GCX) shedding plays a critical role in
      vascular disease. Previous work demonstrated that GCX degradation disrupts
      endothelial cell (EC) gap junction connexin (Cx) proteins, likely blocking
      interendothelial molecular transport that maintains EC and vascular tissue
      homeostasis to resist disease. Here, we focused on GCX regeneration and tested
      the hypothesis that vasculoprotective EC function can be stimulated via
      replacement of GCX when it is shed. We used EC with [i] intact heparan sulfate
      (HS), the most abundant GCX component; [ii] degraded HS; or [iii] HS that was
      restored after enzyme degradation, by cellular self-recovery or artificially.
      Artificial HS restoration was achieved via treatment with exogenous HS, with or
      without the GCX regenerator and protector sphingosine 1- phosphate (S1P). In
      these cells we immunocytochemically examined expression of Cx isotype 43 (Cx43)
      at EC borders and characterized Cx-containing gap junction activity by measuring
      interendothelial spread of gap junction permeable Lucifer Yellow dye. With intact
      HS, 60% of EC borders expressed Cx43 and dye spread to 2.88 +/- 0.09 neighboring
      cells. HS degradation decreased Cx43 expression to 30% and reduced dye spread to
      1.87+/- 0.06 cells. Cellular self-recovery of HS restored baseline levels of Cx43
      and dye transfer. Artificial HS recovery with exogenous HS partially restored
      Cx43 expression to 46% and yielded dye spread to only 1.03 +/- 0.07 cells.
      Treatment with both HS and S1P, recovered HS and restored Cx43 to 56% with
      significant dye transfer to 3.96 +/- 0.23 cells. This is the first evidence of
      GCX regeneration in a manner that effectively restores vasculoprotective EC
      communication.

PMID- 29023480
TI  - Phenoseasonal subcanopy light dynamics and the effects of light on the
      physiological ecology of a common understory shrub, Lindera benzoin.
AB  - The purpose of this work was to quantify the variation of subcanopy
      spatiotemporal light dynamics over the course of a year and to link it to the
      physiological ecology of the understory shrub, Lindera benzoin L. Blume (northern
      spicebush). Covering all seven phenoseasons of a deciduous forest, this work
      utilized a line quantum sensor to measure the variation in subcanopy light levels
      under all sky conditions at different times of the day. A total of 4,592
      individual subcanopy measurements of photosynthetic photon flux density (PPFD,
      MUmol m-2 s-1) were taken as 15-second spatially-integrated one-meter linear
      averages to better understand the dynamism of light exposure to L. benzoin. Both
      open (n = 2, one continuous and one instantaneous) and subcanopy location (n =
      25) measurements of PPFD were taken on each sampling date in and near the
      forested plot (Maryland, USA). In addition, we explored the effect of four
      photointensity-photoperiod combinations on the growth of L. benzoin under
      controlled conditions to compare to field conditions. On average, understory PPFD
      was less than 2% of open PPFD during the leafed months and an average of 38.8% of
      open PPFD during leafless winter months, indicating that: (1) often overlooked
      woody surfaces intercept large amounts of light; and (2) spicebush within the
      plot receive limited light even in early spring before canopy leaf-out.
      Statistical results suggested phenoseason accounted for nearly three-quarters of
      the variation in incident radiation between the three plant canopy heights.
      Spicebush under controlled conditions exhibited the highest fitness levels at an
      intensity of 164.5 MUmol m-2 s-1 for 12-hour duration. Similarly, spicebush
      growth in the field occurred at subcanopy locations receiving higher incidence of
      PPFD (i.e., >128 MUmol m-2 s-1). Results suggest that the ecological niche for
      these plants is very specific in terms of light intensity.

PMID- 29023479
TI  - Evaluating the efficiency of CHEF and CMV promoter with IRES and Furin/2A linker
      sequences for monoclonal antibody expression in CHO cells.
AB  - In recent years, monoclonal antibodies (mAbs) have been developed as powerful
      therapeutic and diagnostic agents and Chinese hamster ovary (CHO) cells have
      emerged as the dominant host for the recombinant expression of these proteins. A
      critical step in recombinant expression is the utilization of strong promoters,
      such as the Chinese Hamster Elongation Factor-1alpha (CHEF-1) promoter. To
      compare the strengths of CHEF with cytomegalovirus (CMV) promoter for mAb
      expression in CHO cells, four bicistronic vectors bearing either internal
      ribosome entry site (IRES) or Furin/2A (F2A) sequences were designed. The
      efficiency of these promoters was evaluated by measuring level of expressed
      antibody in stable cell pools. Our results indicated that CHEF promoter-based
      expression of mAbs was 2.5 fold higher than CMV-based expression in F2A-mediated
      vectors. However, this difference was less significant in IRES-mediated mAb
      expressing cells. Studying the stability of the F2A expression system in the
      course of 18 weeks, we observed that the cells having CHEF promoter maintained
      their antibody expression at higher level than those transfected with CMV
      promoter. Further analyses showed that both IRES-mediated vectors, expressed mAbs
      with correct size, whereas in antibodies expressed via F2A system heterogeneity
      of light chains were detected due to incomplete furin cleavage. Our findings
      indicated that the CHEF promoter is a viable alternative to CMV promoter-based
      expression in F2A-mediated vectors by providing both higher expression and level
      of stability.

PMID- 29023481
TI  - Phytochemical residue profiles in rice grains fumigated with essential oils for
      the control of rice weevil.
AB  - In the present study, we investigated the fumigant potential of five edible
      essential oils (EOs) against Sitophilus oryzae and their phytochemical residues
      in treated grains. Among the tested EOs, peppermint oil proved significantly
      effective (P <= 0.05) on S.oryzae at 400 MUl/L air concentration, inducing 83 and
      100% mortalities in with-food and without-food conditions respectively over 72 h
      exposure. In addition, it was also observed that the binary mixtures of
      peppermint + lemon oil (1:1 ratio) produced an equivalent effect to that of
      peppermint oil alone treatments. The phytochemical residue analysis by GC-MS
      revealed the presence of six compounds upon 72 h exposure to EOs. Further, the
      analysis of physico-chemical properties of the compounds indicated a positive
      correlation between polar surface area (PSA) and its residual nature. The residue
      levels of eugenol were significantly elevated corresponding to its high PSA value
      (29) in clove and cinnamon oils. On the other hand, the compounds with zero PSA
      value imparted very less or no (D-Limonene, caryophyllene, pinene and
      terpinolene) residues in treated grains. With respect to the most active
      peppermint oil, L-menthone, menthyl acetate and eucalyptol residues were at 67,
      41 and 23% levels respectively. The outcome of the present study indicate the
      peppermint oil as a potent fumigant against S. oryzae, and although the residues
      of phytochemicals in treated grains is higher; they belong to the generally
      recognised as safe (GRAS) status leaving no harmful effect.

PMID- 29023482
TI  - The trade-off between morphology and control in the co-optimized design of
      robots.
AB  - Conventionally, robot morphologies are developed through simulations and
      calculations, and different control methods are applied afterwards. Assuming that
      simulations and predictions are simplified representations of our reality, how
      sure can roboticists be that the chosen morphology is the most adequate for the
      possible control choices in the real-world? Here we study the influence of the
      design parameters in the creation of a robot with a Bayesian morphology-control
      (MC) co-optimization process. A robot autonomously creates child robots from a
      set of possible design parameters and uses Bayesian Optimization (BO) to infer
      the best locomotion behavior from real world experiments. Then, we systematically
      change from an MC co-optimization to a control-only (C) optimization, which
      better represents the traditional way that robots are developed, to explore the
      trade-off between these two methods. We show that although C processes can
      greatly improve the behavior of poor morphologies, such agents are still
      outperformed by MC co-optimization results with as few as 25 iterations. Our
      findings, on one hand, suggest that BO should be used in the design process of
      robots for both morphological and control parameters to reach optimal
      performance, and on the other hand, point to the downfall of current design
      methods in face of new search techniques.

PMID- 29023483
TI  - A simpler and more cost-effective peptide biosynthetic method using the truncated
      GST as carrier for epitope mapping.
AB  - There is a need to develop better methods for epitope mapping and/or
      identification of antibody-recognizing motifs. Here, we describe improved
      biosynthetic peptide (BSP) method using a newly developed plasmid pXXGST-3 as
      vector, which has a viral E7 gene in the cloning sites of pXXGST-1. It is crucial
      to employ pXXGST-3 instead of pXXGST-1, since it makes use of the BSP method
      simpler and easier to perform, and more cost-effective for epitope mapping. These
      merits are embodied in two aspects: i) convenient recovery of double enzyme
      digested product due to the existence of 315 bp inserted between BamH I and Sal I
      sites, and thus greatly reducing the production of self-ligation clones, and ii)
      no longer requiring control protein when screening recombinant (r-) clones
      expressing 8/18mer peptides by running polyacrylamide gel electrophoresis. The
      protocol involves the following core steps: (i) design of plus and minus strands
      of DNA fragments encoding overlapping 8/18mer peptides; (ii) chemical synthesis
      of the designed DNA fragments; (iii) development of r-clones using pXXGST-3
      vector expressing each 8/18mer peptide fused with truncated GST188 protein; (iv)
      screening r-clones by running the cell pellets from each induced clone on SDS
      PAGE gel followed by sequencing of inserted DNA fragments for each verified r
      clone; and (v) Western blotting with either monoclonal antibodies or polyclonal
      antibodies. This improved GST188-BSP method provides a powerful alternative tool
      for epitope mapping.

PMID- 29023484
TI  - Does density-dependent diversification mirror ecological competitive exclusion?
AB  - Density-dependence is a term used in ecology to describe processes such as birth
      and death rates that are regulated by the number of individuals in a population.
      Evolutionary biologists have borrowed the term to describe decreasing rates of
      species accumulation, suggesting that speciation and extinction rates depend on
      the total number of species in a clade. If this analogy with ecological density
      dependence holds, diversification of clades is restricted because species compete
      for limited resources. We hypothesize that such competition should not only
      affect numbers of species, but also prevent species from being phenotypically
      similar. Here, we present a method to detect whether competitive interactions
      between species have ordered phenotypic traits on a phylogeny, assuming that
      competition prevents related species from having identical trait values. We use
      the method to analyze clades of birds and mammals, with body size as the
      phenotypic trait. We find no sign that competition has prevented species from
      having the same body size. Thus, since body size is a key ecological trait and
      competition does not seem to be responsible for differences in body size between
      species, we conclude that the diversification slowdown that is prevalent in these
      clades is unlikely due to the ecological interference implied by the term density
      dependence.

PMID- 29023485
TI  - A degradation-based sorting method for lithium-ion battery reuse.
AB  - In a world where millions of people are dependent on batteries to provide them
      with convenient and portable energy, battery recycling is of the utmost
      importance. In this paper, we developed a new method to sort 18650 Lithium-ion
      batteries in large quantities and in real time for harvesting used cells with
      enough capacity for battery reuse. Internal resistance and capacity tests were
      conducted as a basis for comparison with a novel degradation-based method based
      on X-ray radiographic scanning and digital image contrast computation. The test
      results indicate that the sorting accuracy of the test cells is about 79% and the
      execution time of our algorithm is at a level of 200 milliseconds, making our
      method a potential real-time solution for reusing the remaining capacity in good
      used cells.

PMID- 29023487
TI  - Triggers of acute attacks of gout, does age of gout onset matter? A primary care
      based cross-sectional study.
AB  - OBJECTIVES: To determine the proportion of people with gout who self-report
      triggers of acute attacks; identify the commonly reported triggers, and examine
      the disease and demographic features associated with self-reporting any
      trigger(s) of acute attacks of gout. METHODS: Individuals with gout were asked to
      fill a questionnaire enquiring about triggers that precipitated their acute gout
      attacks. Binary logistic regression was used to compute odds ratio (OR) and 95%
      confidence intervals (CI) to examine the association between having >=1 self
      reported trigger of acute gout and disease and demographic risk factors and to
      adjust for covariates. All statistical analyses were performed using STATA.
      RESULTS: 550 participants returned completed questionnaires. 206 (37.5%) reported
      at least one trigger of acute attacks, and less than 5% reported >2 triggers.
      Only 28.73% participants reported that their most recent gout attack was
      triggered by dietary or lifestyle risk factors. The most frequently self-reported
      triggers were alcohol intake (14.18%), red-meat or sea-food consumption (6%),
      dehydration (4.91%), injury or excess activity (4.91%), and excessively warm or
      cold weather (4.36% and 5.45%). Patients who had onset of gout before the age of
      50 years were significantly more likely to identify a trigger for precipitating
      their acute gout attacks (aOR (95%CI) 1.73 (1.12-2.68) after adjusting for
      covariates. CONCLUSION: Most people with gout do not identify any triggers for
      acute attacks, and identifiable triggers are more common in those with young
      onset gout. Less than 20% people self-reported acute gout attacks from
      conventionally accepted triggers of gout e.g. alcohol, red-meat intake, while
      c.5% reported novel triggers such as dehydration, injury or physical activity,
      and weather extremes.

PMID- 29023488
TI  - Transgenic expression of human cytokines in immunodeficient mice does not
      facilitate myeloid expansion of BCR-ABL1 transduced human cord blood cells.
AB  - Several attempts have been made to model chronic myeloid leukemia (CML) in a
      xenograft setting but expansion of human myeloid cells in immunodeficient mice
      has proven difficult to achieve. Lack of cross-reacting cytokines in the
      microenvironment of the mice has been proposed as a potential reason. In this
      study we have used NOD/SCID IL2-receptor gamma deficient mice expressing human
      SCF, IL-3 and GM-CSF (NSGS mice), that should be superior in supporting human,
      and particularly, myeloid cell engraftment, to expand BCR-ABL1 expressing human
      cells in order to model CML. NSGS mice transplanted with BCR-ABL1 expressing
      cells became anemic and had to be sacrificed due to illness, however, this was
      not accompanied by an expansion of human myeloid cells but rather we observed a
      massive expansion of human T-cells and macrophages/histiocytes. Importantly,
      control human cells without BCR-ABL1 expression elicited a similar reaction,
      although with a slight delay of disease induction, suggesting that while BCR-ABL1
      contributes to the inflammatory reaction, the presence of normal human
      hematopoietic cells is detrimental for NSGS mice.

PMID- 29023486
TI  - The sea cucumber genome provides insights into morphological evolution and
      visceral regeneration.
AB  - Apart from sharing common ancestry with chordates, sea cucumbers exhibit a unique
      morphology and exceptional regenerative capacity. Here we present the complete
      genome sequence of an economically important sea cucumber, A. japonicus,
      generated using Illumina and PacBio platforms, to achieve an assembly of
      approximately 805 Mb (contig N50 of 190 Kb and scaffold N50 of 486 Kb), with
      30,350 protein-coding genes and high continuity. We used this resource to explore
      key genetic mechanisms behind the unique biological characters of sea cucumbers.
      Phylogenetic and comparative genomic analyses revealed the presence of marker
      genes associated with notochord and gill slits, suggesting that these chordate
      features were present in ancestral echinoderms. The unique shape and weak
      mineralization of the sea cucumber adult body were also preliminarily explained
      by the contraction of biomineralization genes. Genome, transcriptome, and
      proteome analyses of organ regrowth after induced evisceration provided insight
      into the molecular underpinnings of visceral regeneration, including a specific
      tandem-duplicated prostatic secretory protein of 94 amino acids (PSP94)-like gene
      family and a significantly expanded fibrinogen-related protein (FREP) gene
      family. This high-quality genome resource will provide a useful framework for
      future research into biological processes and evolution in deuterostomes,
      including remarkable regenerative abilities that could have medical applications.
      Moreover, the multiomics data will be of prime value for commercial sea cucumber
      breeding programs.

PMID- 29023489
TI  - Spatiotemporal variations in gene expression, histology and biomechanics in an
      ovine model of tendinopathy.
AB  - Flexor tendinopathy is a common problem affecting humans and animals. Tendon
      healing is poorly understood and the outcomes of conservative and surgical
      management are often suboptimal. While often considered a localized injury,
      recent evidence indicates that in the short term, tendinopathic changes are
      distributed widely throughout the tendon, remote from the lesion itself. Whether
      these changes persist throughout healing is unknown. The aim of this study was to
      document gene expression, histopathological and biomechanical changes that occur
      throughout the superficial digital flexor tendon (SDFT) up to 16 weeks post
      injury, using an ovine surgical model of tendinopathy. Partial tendon transection
      was associated with decreased gene expression for aggrecan, decorin,
      fibromodulin, tissue inhibitors of metalloproteinases (TIMPS 1, 2 and 3),
      collagen I and collagen II. Gene expression for collagen III, lumican and matrix
      metalloproteinase 13 (MMP13) increased locally around the lesion site. Expression
      of collagen III and MMP13 decreased with time, but compared to controls, collagen
      III, MMP13 and lumican expression remained regionally high throughout the study.
      An increase in TIMP3 was observed over time. Histologically, operated tendons had
      higher pathology scores than controls, especially around the injured region. A
      chondroid phenotype was observed with increased cellular rounding and marked
      proteoglycan accumulation which only partially improved with time.
      Biomechanically, partial tendon transection resulted in a localized decrease in
      elastic modulus (in compression) but only at 8 weeks postoperatively. This study
      improves our understanding of tendon healing, demonstrating an early 'peak' in
      pathology characterized by altered gene expression and notable histopathological
      changes. Many of these pathological changes become more localized to the region
      of injury during healing. Collagen III and MMP13 expression levels remained high
      close to the lesion throughout the study and may reflect the production of tendon
      tissue with suboptimal biomechanical properties. Further studies evaluating the
      long-term response of tendon to injury (6-12 months) are warranted to provide
      additional information on tendon healing and provide further understanding of the
      mechanisms underlying the pathology observed in this study.

PMID- 29023490
TI  - Network modeling of kinase inhibitor polypharmacology reveals pathways targeted
      in chemical screens.
AB  - Small molecule screens are widely used to prioritize pharmaceutical development.
      However, determining the pathways targeted by these molecules is challenging,
      since the compounds are often promiscuous. We present a network strategy that
      takes into account the polypharmacology of small molecules in order to generate
      hypotheses for their broader mode of action. We report a screen for kinase
      inhibitors that increase the efficacy of gemcitabine, the first-line chemotherapy
      for pancreatic cancer. Eight kinase inhibitors emerge that are known to affect
      201 kinases, of which only three kinases have been previously identified as
      modifiers of gemcitabine toxicity. In this work, we use the SAMNet algorithm to
      identify pathways linking these kinases and genetic modifiers of gemcitabine
      toxicity with transcriptional and epigenetic changes induced by gemcitabine that
      we measure using DNaseI-seq and RNA-seq. SAMNet uses a constrained optimization
      algorithm to connect genes from these complementary datasets through a small set
      of protein-protein and protein-DNA interactions. The resulting network
      recapitulates known pathways including DNA repair, cell proliferation and the
      epithelial-to-mesenchymal transition. We use the network to predict genes with
      important roles in the gemcitabine response, including six that have already been
      shown to modify gemcitabine efficacy in pancreatic cancer and ten novel
      candidates. Our work reveals the important role of polypharmacology in the
      activity of these chemosensitizing agents.

PMID- 29023493
TI  - New perspective on single-radiator multiple-port antennas for adaptive
      beamforming applications.
AB  - One of the most challenging problems in recent antenna engineering fields is to
      achieve highly reliable beamforming capabilities in an extremely restricted space
      of small handheld devices. In this paper, we introduce a new perspective on
      single-radiator multiple-port (SRMP) antenna to alter the traditional approach of
      multiple-antenna arrays for improving beamforming performances with reduced
      aperture sizes. The major contribution of this paper is to demonstrate the
      beamforming capability of the SRMP antenna for use as an extremely miniaturized
      front-end component in more sophisticated beamforming applications. To examine
      the beamforming capability, the radiation properties and the array factor of the
      SRMP antenna are theoretically formulated for electromagnetic characterization
      and are used as complex weights to form adaptive array patterns. Then, its
      fundamental performance limits are rigorously explored through enumerative
      studies by varying the dielectric constant of the substrate, and field tests are
      conducted using a beamforming hardware to confirm the feasibility. The results
      demonstrate that the new perspective of the SRMP antenna allows for improved
      beamforming performances with the ability of maintaining consistently smaller
      aperture sizes compared to the traditional multiple-antenna arrays.

PMID- 29023492
TI  - Filter quality of electret masks in filtering 14.6-594 nm aerosol particles:
      Effects of five decontamination methods.
AB  - This study investigates the effects of five decontamination methods on the filter
      quality (qf) of three commercially available electret masks-N95, Gauze and
      Spunlace nonwoven masks. Newly developed evaluation methods, the overall filter
      quality (qf,o) and the qf ratio were applied to evaluate the effectiveness of
      decontamination methods for respirators. A scanning mobility particle sizer is
      utilized to measure the concentration of polydispersed particles with diameter
      14.6-594 nm. The penetration of particles and pressure drop (Deltap) through the
      mask are used to determine qf and qf,o. Experimental results reveal that the most
      penetrating particle size (MPS) for the pre-decontaminated N95, Gauze and
      Spunlace masks were 118 nm, 461 nm and 279 nm, respectively, and the respective
      penetration rates were 2.6%, 23.2% and 70.0%. The Deltap through the pretreated
      N95 masks was 9.2 mm H2O at the breathing flow rate of heavy-duty workers,
      exceeding the Deltap values obtained through Gauze and Spunlace masks.
      Decontamination increased the sizes of the most penetrating particles, changing
      the qf values of all of the masks: qf fell as particle size increased because the
      penetration increased. Bleach increased the Deltap of N95, but destroyed the
      Gauze mask. However, the use of an autoclave reduces the Deltap values of both
      the N95 and the Gauze mask. Neither the rice cooker nor ethanol altered the
      Deltap of the Gauze mask. Chemical decontamination methods reduced the qf,o
      values for the three electret masks. The value of qf,o for PM0.1 exceeded that
      for PM0.1-0.6, because particles smaller than 100 nm had lower penetration,
      resulting in a better qf for a given pressure drop. The values of qf,o,
      particularly for PM0.1, reveal that for the tested treatments and masks, physical
      decontamination methods are less destructive to the filter than chemical methods.
      Nevertheless, when purchasing new or reusing FFRs, penetration should be regarded
      as the priority.

PMID- 29023491
TI  - Efficacy of carbonic anhydrase inhibitors in management of cystoid macular edema
      in retinitis pigmentosa: A meta-analysis.
AB  - BACKGROUND: Carbonic anhydrase inhibitors (CAI) are often used in the treatment
      of cystoid macular edema (CME) in retinitis pigmentosa (RP) patients. The aim of
      this meta-analysis is to gain a better understanding of the overall efficacy of
      CAI treatment. METHODS: Databases including PubMed, EMBASE, and Cochrane Library
      were searched to identify relevant studies. Eligible studies were clinical trials
      of patients with RP assigned topical or oral CAIs such as dorzolamide and
      acetazolamide. Changes in central macular thickness (CMT) by OCT in MUm and best
      corrected visual acuity (BCVA) in log MAR equivalents were extracted and results
      compared between baseline and after treatment. RESULTS: 11 clinical reports were
      identified which included a total of 194 patients (358 eyes) available for
      analysis, with 59 patients (115 eyes) assigned oral CAI treatment and 135
      patients (243 eyes) assigned topical CAI treatment. The combined results showed a
      significant reduction of macular edema, as calculated by baseline and final
      central macular thickness (CMT) based on OCT examination (46.02MUm, 95%CI: 
      60.96, -31.08, I2 = 65%). However, the effect on visual acuity was inconsistent
      across studies. CONCLUSION: Based on non randomized controlled clinical studies,
      RP patients with CME who were treated with CAIs had better anatomical outcomes,
      but the effect on visual acuity was contradictory across studies. Multicenter
      prospective randomized controlled trials would be ideal to definitively test its
      clinical efficacy in RP patients.

PMID- 29023496
TI  - Pacing the phasing of leg and arm movements in breaststroke swimming to minimize
      intra-cyclic velocity fluctuations.
AB  - In swimming propelling efficiency is partly determined by intra-cyclic velocity
      fluctuations. The higher these fluctuations are at a given average swimming
      velocity, the less efficient is the propulsion. This study explored whether the
      leg-arm coordination (i.e. phase relation phi) within the breaststroke cycle can
      be influenced with acoustic pacing, and whether the so induced changes are
      accompanied by changes in intra-cyclic velocity fluctuations. Twenty-six
      participants were asked to couple their propulsive leg and arm movements to a
      double-tone metronome beat and to keep their average swimming velocity constant
      over trials. The metronome imposed five different phase relations phii (90, 135,
      180, 225 and 270 degrees ) of leg-arm coordination. Swimmers adjusted their
      technique under the influence of the metronome, but failed to comply to the
      velocity requirement for phi = 90 and 135 degrees . For imposed phi = 180, 225
      and 270 degrees , the intra-cyclic velocity fluctuations increased with
      increasing phi, while average swimming velocity did not differ. This suggests
      that acoustic pacing may be used to adjust phi and thereby performance of
      breaststroke swimming given the dependence of propelling efficiency on phi.

PMID- 29023494
TI  - Pooled analysis of menstrual irregularities from three major clinical studies
      evaluating everolimus for the treatment of tuberous sclerosis complex.
AB  - OBJECTIVES: To determine the impact of everolimus on female fertility, including
      menstrual irregularities, secondary amenorrhea, and luteinizing and follicle
      stimulating hormone levels in female patients. DESIGN: A pooled analysis from 3
      prospective studies consisting of a core phase (>=6 months) and a long-term
      follow-up open-label extension. SETTING: One phase 2 single-center and two phase
      3 multicenter studies. PARTICIPANTS: Data were obtained from female participants,
      restricted to those between 10 and 55 years of age, during 1 of 3 of the
      described clinical trials of everolimus. Patients had received >= 1 dose of
      everolimus. MAIN OUTCOME MEASURES: Incidence of fertility events. RESULTS: A
      total of 43/112 patients (38.4%) experienced at least 1 menstrual irregularity.
      The most common events were amenorrhea (24.1%) and irregular menstruation
      (17.0%). Seven patients (6.3%) experienced grade 3/4 amenorrhea. When only the
      longest duration period of amenorrhea for each patient was considered, the median
      duration was 291 days. Fifteen patients attained menarche during the treatment
      period in any of the pooled studies. The mean age of menarche for this group was
      12.4 years, similar to that of patients who were postmenarche at study entry
      (12.2 years). A total of 19/92 patients (20.7%) who were postmenarche at baseline
      or during the study experienced an irregular menstruation event. An increased
      luteinizing hormone level was reported as an adverse event in 3/112 patients
      (3%), and follicle-stimulating hormone levels were within normal limits for these
      patients. CONCLUSIONS: No new safety concerns emerged regarding endocrine
      function and menstruation in female patients with tuberous sclerosis complex
      associated subependymal giant cell astrocytoma or angiomyolipoma, who were
      receiving everolimus. TRIAL REGISTRATION: ClinicalTrials.gov NCT00411619,
      NCT00789828, NCT00790400.

PMID- 29023495
TI  - The hnRNP-like Nab3 termination factor can employ heterologous prion-like domains
      in place of its own essential low complexity domain.
AB  - Many RNA-binding proteins possess domains with a biased amino acid content. A
      common property of these low complexity domains (LCDs) is that they assemble into
      an ordered amyloid form, juxtaposing RNA recognition motifs in a subcellular
      compartment in which RNA metabolism is focused. Yeast Nab3 is one such protein
      that contains RNA-binding domains and a low complexity, glutamine/proline-rich,
      prion-like domain that can self-assemble. Nab3 also contains a region of
      structural homology to human hnRNP-C that resembles a leucine zipper which can
      oligomerize. Here we show that the LCD and the human hnRNP-C homology domains of
      Nab3 were experimentally separable, as cells were viable with either segment, but
      not when both were missing. In exploiting the lethality of deleting these regions
      of Nab3, we were able to test if heterologous prion-like domains known to
      assemble into amyloid, could substitute for the native sequence. Those from the
      hnRNP-like protein Hrp1, the canonical prion Sup35, or the epsin-related protein
      Ent2, could rescue viability and enable the new Nab3 chimeric protein to support
      transcription termination. Other low complexity domains from RNA-binding,
      termination-related proteins or a yeast prion, could not. As well, an unbiased
      genetic selection revealed a new protein sequence that could rescue the loss of
      Nab3's essential domain via multimerization. This new sequence and Sup35's prion
      domain could also rescue the lethal loss of Hrp1's prion-like domain when
      substituted for it. This suggests there are different cross-functional classes of
      amyloid-forming LCDs and that appending merely any assembly-competent LCD to Nab3
      does not restore function or rescue viability. The analysis has revealed the
      functional complexity of LCDs and provides a means by which the differing classes
      of LCD can be dissected and understood.

PMID- 29023498
TI  - Incidence and risk factors of massive subretinal hemorrhage in retinal
      angiomatous proliferation.
AB  - OBJECTIVE: To evaluate the incidence and associated risk factors of massive
      subretinal hemorrhage (SRH) in patients with retinal angiomatous proliferation
      (RAP). METHODS: A total of 187 eyes of 135 treatment-naive patients diagnosed
      with RAP were evaluated retrospectively. Clinical records including the time
      between the initial visit, last anti-vascular endothelial growth factor (VEGF)
      treatment, last stable examination, and the date of massive SRH were reviewed.
      Imaging findings including indocyanine green angiography (ICGA) and optical
      coherence tomography (OCT) were analyzed. RESULTS: Massive SRH developed in 18
      eyes (9.6%) a median of 20 months after the initial presentation. Kaplan-Meier
      survival analysis revealed that the incidence (2.8, 5.8, 13.1, and 21.0% after
      1,2,5 and 10 years, respectively) continuously increased. Among 14 eyes with
      discernable vascular anastomosis on baseline ICGA, 13 (92.8%) showed retinal
      arteriole involvement. On spectral-domain OCT imaging of the last visit prior to
      the massive SRH, a layered lamellar tissue complex was noted under the retinal
      pigment epithelium in 9 of 13 eyes, which was significantly associated with
      massive SRH[hazard ratio(HR),5.883;P = .010]. The average time between the last
      stable examination/last injection and the massive SRH was 2 and 5 months,
      respectively. The patients were treated with anti-VEGF, gas and recombinant
      tissue plasminogen activator injection; however, all except one eye had visual
      acuity worse than 20/1000 at the final visit. CONCLUSIONS: Massive SRH can occur
      in RAP in the course of anti-VEGF treatment, resulting in severe vision loss. A
      proactive dosing regimen may be more appropriate for these RAP eyes.

PMID- 29023499
TI  - Understanding the perceived logic of care by vaccine-hesitant and vaccine
      refusing parents: A qualitative study in Australia.
AB  - In terms of public health, childhood vaccination programs have benefits that far
      outweigh risks. However, some parents decide not to vaccinate their children.
      This paper explores the ways in which such parents talked about the perceived
      risks and benefits incurred by vaccinating (or not vaccinating) their children.
      Between 2013-2016 we undertook 29 in-depth interviews with non-vaccinating and/or
      'vaccine hesitant' parents in Australia. Interviews were conducted in an open and
      non-judgmental manner, akin to empathic neutrality. Interviews focused on parents
      talking about the factors that shaped their decisions not to (or partially)
      vaccinate their children. All interviews were transcribed and analysed using both
      inductive and deductive processes. The main themes focus on parental perceptions
      of: 1. their capacity to reason; 2. their rejection of Western medical
      epistemology; and 3. their participation in labour intensive parenting practices
      (which we term salutogenic parenting). Parents engaged in an ongoing search for
      information about how best to parent their children (capacity to reason), which
      for many led to questioning/distrust of traditional scientific knowledge
      (rejection of Western medical epistemology). Salutogenic parenting spontaneously
      arose in interviews, whereby parents practised health promoting activities which
      they saw as boosting the natural immunity of their children and protecting them
      from illness (reducing or negating the perceived need for vaccinations).
      Salutogenic parenting practices included breastfeeding, eating organic and/or
      home-grown food, cooking from scratch to reduce preservative consumption and
      reducing exposure to toxins. We interpret our data as a 'logic of care', which is
      seen by parents as internally consistent, logically inter-related and inter
      dependent. Whilst not necessarily sharing the parents' reasoning, we argue that
      an understanding of their attitudes towards health and well-being is imperative
      for any efforts to engage with their vaccine refusal at a policy level.

PMID- 29023497
TI  - Characterization of PAX9 variant P20L identified in a Japanese family with tooth
      agenesis.
AB  - Transcription factors PAX9 and MSX1 play crucial roles in the development of
      permanent teeth at the bud stage, and their loss-of-function variants have been
      associated with congenital tooth agenesis. We sequenced the coding regions of the
      PAX9 and MSX1 genes from nine patients with non-syndromic tooth agenesis, and
      identified a missense mutation, P20L, of PAX9 in a single familial case involving
      three patients in two generations. Identical mutation was previously reported by
      other authors, but has not been characterized in detail. The mutation was located
      in a highly conserved N-terminal subdomain of the paired domain and co-segregated
      as a heterozygote with tooth agenesis. The patients showed defects primarily in
      the first and second molars, which is typical for cases attributable to PAX9
      mutation. Luciferase reporter assay using the 2.3-kb promoter region of BMP4 and
      electrophoretic mobility shift assay using the CD19-2(A-ins) sequence revealed
      that P20L substitution eliminated most of the transactivation activity and
      specific DNA binding activity of PAX9 under the experimental conditions we
      employed, while some residual activity of the mutant was evident in the former
      assay. The hypomorphic nature of the variant may explain the relatively mild
      phenotype in this case, as compared with other PAX9 pathogenic variants such as
      R26W.

PMID- 29023500
TI  - The ghosts of HeLa: How cell line misidentification contaminates the scientific
      literature.
AB  - While problems with cell line misidentification have been known for decades, an
      unknown number of published papers remains in circulation reporting on the wrong
      cells without warning or correction. Here we attempt to make a conservative
      estimate of this 'contaminated' literature. We found 32,755 articles reporting on
      research with misidentified cells, in turn cited by an estimated half a million
      other papers. The contamination of the literature is not decreasing over time and
      is anything but restricted to countries in the periphery of global science. The
      decades-old and often contentious attempts to stop misidentification of cell
      lines have proven to be insufficient. The contamination of the literature calls
      for a fair and reasonable notification system, warning users and readers to
      interpret these papers with appropriate care.

PMID- 29023502
TI  - Process oriented guided inquiry learning (POGIL(r)) marginally effects student
      achievement measures but substantially increases the odds of passing a course.
AB  - While the inquiry approach to science teaching has been widely recommended as an
      epistemic mechanism to promote deep content understanding, there is also
      increased expectation that process and other transferable skills should be
      integral part of science pedagogy. To test the hypothesis that coupling process
      skills to content teaching impacts academic success measures, we meta-analyzed
      twenty-one studies (n = 21) involving 7876 students that compared Process
      Oriented Guided Inquiry Learning (POGIL), a pedagogy that provides opportunities
      for improving process skills during content learning through guided-inquiry
      activities, to standard lecture conditions. Based on conventional measures of
      class performance, POGIL had a small effect on achievement outcomes (effect size
      = 0.29, [95% CI = 0.15-0.43]) but substantially improved the odds of passing a
      class (odds ratio = 2.02, [95% CI: 1.45-2.83]). That is, participants in the
      POGIL pedagogy had higher odds of passing a course and roughly performed 0.3
      standard deviations higher on achievement measures than participants in standard
      lectures. In relative risk terms, POGIL reduced the risk of failing a course by
      38%. These findings suggest providing opportunities to improve process skills
      during class instruction does not inhibit content learning but enhances
      conventional success measures. We compare these findings with those of recent
      large meta-analysis that examined the effects of global active learning methods
      on achievement outcomes and course failure rates in science, technology,
      engineering, and mathematics (STEM) fields.

PMID- 29023501
TI  - Cognitive processing of orientation discrimination in anisometropic amblyopia.
AB  - Cognition is very important in our daily life. However, amblyopia has abnormal
      visual cognition. Physiological changes of the brain during processes of
      cognition could be reflected with ERPs. So the purpose of this study was to
      investigate the speed and the capacity of resource allocation in visual cognitive
      processing in orientation discrimination task during monocular and binocular
      viewing conditions of amblyopia and normal control as well as the corresponding
      eyes of the two groups with ERPs. We also sought to investigate whether the speed
      and the capacity of resource allocation in visual cognitive processing vary with
      target stimuli at different spatial frequencies (3, 6 and 9 cpd) in amblyopia and
      normal control as well as between the corresponding eyes of the two groups.
      Fifteen mild to moderate anisometropic amblyopes and ten normal controls were
      recruited. Three-stimulus oddball paradigms of three different spatial frequency
      orientation discrimination tasks were used in monocular and binocular conditions
      in amblyopes and normal controls to elicit event-related potentials (ERPs).
      Accuracy (ACC), reaction time (RT), the latency of novelty P300 and P3b, and the
      amplitude of novelty P300 and P3b were measured. Results showed that RT was
      longer in the amblyopic eye than in both eyes of amblyopia and non-dominant eye
      in control. Novelty P300 amplitude was largest in the amblyopic eye, followed by
      the fellow eye, and smallest in both eyes of amblyopia. Novelty P300 amplitude
      was larger in the amblyopic eye than non-dominant eye and was larger in fellow
      eye than dominant eye. P3b latency was longer in the amblyopic eye than in the
      fellow eye, both eyes of amblyopia and non-dominant eye of control. P3b latency
      was not associated with RT in amblyopia. Neural responses of the amblyopic eye
      are abnormal at the middle and late stages of cognitive processing, indicating
      that the amblyopic eye needs to spend more time or integrate more resources to
      process the same visual task. Fellow eye and both eyes in amblyopia are slightly
      different from the dominant eye and both eyes in normal control at the middle and
      late stages of cognitive processing. Meanwhile, abnormal extents of amblyopic eye
      do not vary with three different spatial frequencies used in our study.

PMID- 29023503
TI  - Model uncertainties do not affect observed patterns of species richness in the
      Amazon.
AB  - BACKGROUND: Climate change is arguably a major threat to biodiversity
      conservation and there are several methods to assess its impacts on species
      potential distribution. Yet the extent to which different approaches on species
      distribution modeling affect species richness patterns at biogeographical scale
      is however unaddressed in literature. In this paper, we verified if the expected
      responses to climate change in biogeographical scale-patterns of species richness
      and species vulnerability to climate change-are affected by the inputs used to
      model and project species distribution. METHODS: We modeled the distribution of
      288 vertebrate species (amphibians, birds and mammals), all endemic to the Amazon
      basin, using different combinations of the following inputs known to affect the
      outcome of species distribution models (SDMs): 1) biological data type, 2)
      modeling methods, 3) greenhouse gas emission scenarios and 4) climate forecasts.
      We calculated uncertainty with a hierarchical ANOVA in which those different
      inputs were considered factors. RESULTS: The greatest source of variation was the
      modeling method. Model performance interacted with data type and modeling method.
      Absolute values of variation on suitable climate area were not equal among
      predictions, but some biological patterns were still consistent. All models
      predicted losses on the area that is climatically suitable for species,
      especially for amphibians and primates. All models also indicated a current East
      western gradient on endemic species richness, from the Andes foot downstream the
      Amazon river. Again, all models predicted future movements of species upwards the
      Andes mountains and overall species richness losses. CONCLUSIONS: From a
      methodological perspective, our work highlights that SDMs are a useful tool for
      assessing impacts of climate change on biodiversity. Uncertainty exists but
      biological patterns are still evident at large spatial scales. As modeling
      methods are the greatest source of variation, choosing the appropriate statistics
      according to the study objective is also essential for estimating the impacts of
      climate change on species distribution. Yet from a conservation perspective, we
      show that Amazon endemic fauna is potentially vulnerable to climate change, due
      to expected reductions on suitable climate area. Climate-driven faunal movements
      are predicted towards the Andes mountains, which might work as climate refugia
      for migrating species.

PMID- 29023504
TI  - The potential of small-Unmanned Aircraft Systems for the rapid detection of
      threatened unimproved grassland communities using an Enhanced Normalized
      Difference Vegetation Index.
AB  - The loss of unimproved grassland has led to species decline in a wide range of
      taxonomic groups. Agricultural intensification has resulted in fragmented patches
      of remnant grassland habitat both across Europe and internationally. The
      monitoring of remnant patches of this habitat is critically important, however,
      traditional surveying of large, remote landscapes is a notoriously costly and
      difficult task. The emergence of small-Unmanned Aircraft Systems (sUAS) equipped
      with low-cost multi-spectral cameras offer an alternative to traditional
      grassland survey methods, and have the potential to progress and innovate the
      monitoring and future conservation of this habitat globally. The aim of this
      article is to investigate the potential of sUAS for rapid detection of threatened
      unimproved grassland and to test the use of an Enhanced Normalized Difference
      Vegetation Index (ENDVI). A sUAS aerial survey is undertaken at a site nationally
      recognised as an important location for fragmented unimproved mesotrophic
      grassland, within the south east of England, UK. A multispectral camera is used
      to capture imagery in the visible and near-infrared spectrums, and the ENDVI
      calculated and its discrimination performance compared to a range of more
      traditional vegetation indices. In order to validate the results of analysis,
      ground quadrat surveys were carried out to determine the grassland communities
      present. Quadrat surveys identified three community types within the site;
      unimproved grassland, improved grassland and rush pasture. All six vegetation
      indices tested were able to distinguish between the broad habitat types of
      grassland and rush pasture; whilst only three could differentiate vegetation at a
      community level. The Enhanced Normalized Difference Vegetation Index (ENDVI) was
      the most effective index when differentiating grasslands at the community level.
      The mechanisms behind the improved performance of the ENDVI are discussed and
      recommendations are made for areas of future research and study.

PMID- 29023505
TI  - End-member modeling of the grain-size record of Sikouzi fine sediments in Ningxia
      (China) and implications for temperature control of Neogene evolution of East
      Asian winter monsoon.
AB  - The Late Cenozoic East Asian winter monsoon (EAWM) enhancement has been
      attributed to several factors, such as uplift of the Tibetan Plateau, retreat of
      the Paratethys Sea, and global cooling related to polar ice volume increment.
      However, the fundamental forcing factors remain enigmatic due to the absence of
      long and continuous climate records and sensitive indicators. Here we reanalyzed
      the published grain-size record of Sikouzi fine sediments in the western Chinese
      Loess Plateau through end-member (EM) modeling. The results indicate that EM 2
      with grain-size peaks between 10-100 MUm decreased in content from 20.1 to 17 Ma
      and stepwise increased from 17 to 0.07 Ma during the following six stages (17-15
      Ma, 15-12 Ma, 12-8 Ma, 8-6 Ma, 6-4 Ma and 4-0 Ma). Such varying trends can be
      successively correlated in seven stages with the integrated benthic delta18O
      record, implying that global warming weakened the EAWM from 20.1 to 17 Ma and
      global cooling has stepwise strengthened the EAWM since 17 Ma. Therefore, we
      conclude that global temperature change played a major role on the evolution of
      EAWM during the Neogene period. By contrast, Late Cenozoic palaeogeographic
      reorganization caused by uplift of the Tibetan Plateau and retreat of the
      Paratethys Sea contributed less to the evolutionary evolution of EAWM. Spectral
      analysis of the EM 2 data first provided direct evidence of orbitally influenced
      deposition in the study area and thus the EAWM variations during the Neogene
      period. The 100-kyr period became weak since ~10 Ma, possibly due to the decrease
      in sensitivity of a more stable, continental-scale ice sheet in Antarctica to
      local insolation forcing, deserving further investigation.

PMID- 29023506
TI  - Exopolysaccharides regulate calcium flow in cariogenic biofilms.
AB  - Caries-associated biofilms induce loss of calcium from tooth surfaces in the
      presence of dietary carbohydrates. Exopolysaccharides (EPS) provide a matrix
      scaffold and an abundance of primary binding sites within biofilms. The role of
      EPS in binding calcium in cariogenic biofilms is only partially understood. Thus,
      the aim of the present study is to investigate the relationship between the
      calcium dissolution rates and calcium tolerance of caries-associated bacteria and
      yeast as well as to examine the properties of EPS to quantify its binding
      affinity for dissolved calcium. Calcium dissolution was measured by dissolution
      zones on Pikovskaya's agar. Calcium tolerance was assessed by isothermal
      microcalorimetry (IMC) by adding CaCl2 to the bacterial cultures. Acid-base
      titration and Fourier transform infrared (FTIR) spectroscopy were used to
      identify possible functional groups responsible for calcium binding, which was
      assessed by isothermal titration calorimetry (ITC). Lactobacillus spp. and mutans
      streptococci demonstrated calcium dissolution in the presence of different
      carbohydrates. All strains that demonstrated high dissolution rates also revealed
      higher rates of calcium tolerance by IMC. In addition, acidic functional groups
      were predominantly identified as possible binding sites for calcium ions by acid
      base titration and FTIR. Finally, ITC revealed EPS to have a higher binding
      affinity for calcium compared, for example, to lactic acid. In conclusion, this
      study illustrates the role of EPS in terms of the calcium tolerance of cariogenic
      microbiota by determining the ability of EPS to control free calcium
      concentrations within the biofilms as a self-regulating mode of action in the
      pathogenesis of dental caries.

PMID- 29023507
TI  - Massive immune response against IVIg interferes with response against other
      antigens in mice: A new mode of action?
AB  - Administration of high dose intravenous immunoglobulin (IVIg) is widely used in
      the clinic to treat autoimmune and severe inflammatory diseases. However, its
      mechanisms of action remain poorly understood. We assessed the impact of IVIg on
      immune cell populations using an in vivo ovalbumin (Ova)-immunization mouse
      model. High dose IVIg significantly reduced the Ova-specific antibody response.
      Intriguingly, the results obtained indicate an immediate and massive immune
      reaction against IVIg, as shown by the activation and expansion of B cells and
      CD4+ T cells in the spleen and draining lymph nodes and the production of IVIg
      specific antibodies. We propose that IVIg competes at the T-cell level with the
      response against Ova to explain the immunomodulatory properties of IVIg. Two
      monoclonal antibodies did not succeeded in reproducing the effects of IVIg. This
      suggests that in addition to the mouse response against human constant domains,
      the enormous sequence diversity of IVIg may significantly contribute to this
      massive immune response against IVIg. While correlation of these findings to IVIg
      treated patients remains to be explored, our data demonstrate for the first time
      that IVIg re-directs the immune response towards IVIg and away from a specific
      antigen response.

PMID- 29023509
TI  - Effects of forcefield and sampling method in all-atom simulations of inherently
      disordered proteins: Application to conformational preferences of human amylin.
AB  - Although several computational modelling studies have investigated the
      conformational behaviour of inherently disordered protein (IDP) amylin,
      discrepancies in identifying its preferred solution conformations still exist
      between various forcefields and sampling methods used. Human islet amyloid
      polypeptide has long been a subject of research, both experimentally and
      theoretically, as the aggregation of this protein is believed to be the lead
      cause of type-II diabetes. In this work, we present a systematic forcefield
      assessment using one of the most advanced non-biased sampling techniques, Replica
      Exchange with Solute Tempering (REST2), by comparing the secondary structure
      preferences of monomeric amylin in solution. This study also aims to determine
      the ability of common forcefields to sample a transition of the protein from a
      helical membrane bound conformation into the disordered solution state of amylin.
      Our results demonstrated that the CHARMM22* forcefield showed the best ability to
      sample multiple conformational states inherent for amylin. It is revealed that
      REST2 yielded results qualitatively consistent with experiments and in
      quantitative agreement with other sampling methods, however far more
      computationally efficiently and without any bias. Therefore, combining an
      unbiased sampling technique such as REST2 with a vigorous forcefield testing
      could be suggested as an important step in developing an efficient and robust
      strategy for simulating IDPs.

PMID- 29023508
TI  - Conflicting effects of atazanavir therapy on atherosclerotic risk factors in
      stable HIV patients: A randomized trial of regimen switch to atazanavir.
AB  - : Bilirubin acts as a potent endogenous antioxidant, with higher concentrations
      associated with lower rates of CVD; the antiretroviral drug atazanavir (ATV)
      increases bilirubin levels but may also increase von Willebrand factor levels. We
      tested the hypothesis that increasing endogenous bilirubin using ATV would
      improve cardiometabolic risk factors and vascular function in older patients with
      HIV. Ninety participants were enrolled in two study protocols. In protocol 1, we
      evaluated markers of inflammation, thrombosis, and conduit artery endothelial
      function in subjects on non-ATV containing regimens. Participants were randomly
      assigned to continue baseline treatment or switch to an ATV-based regimen.
      Measurements were made at baseline and 28 days. In the protocol 2, we enrolled 30
      subjects who received atazanavir for more than one year and were compared to the
      aim 1 protocol subjects at baseline. 60 subjects were enrolled in the first
      protocol (mean age 53, +/- 6 years), with 31 randomized to ATV and 29 continuing
      baseline treatment. Atazanavir significantly increased serum total bilirubin
      levels (p<0.001) and acutely but not chronically plasma total antioxidant
      capacity (p<0.001). An increase in von Willebrand Factor (p<0.001) and reduction
      in hs-CRP (p = 0.034) were noted. No changes were seen in either flow-mediated
      endothelium-dependent or vasodilation. In cross-sectional analysis (second
      protocol), similar findings were seen in the baseline attributes of non
      atazanavir-based and long-term atazanavir users. Increasing serum bilirubin
      levels with atazanavir in subjects with HIV reduces hs-CRP, temporarily reduces
      oxidative stress, but increases von Willebrand Factor. Atazanavir does not
      improve endothelial function of conduit arteries. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT03019783.

PMID- 29023510
TI  - Reaching the 'first 90': Gaps in coverage of HIV testing among people living with
      HIV in 16 African countries.
AB  - BACKGROUND: UNAIDS has recently proposed a set of three ambitious targets that,
      if achieved, are predicted to end the AIDS epidemic by 2030. The targets, known
      as 90-90-90, call for 90% of people living with HIV (PLHIV) to know their status,
      90% of PLHIV to receive antiretroviral therapy, and 90% of those on
      antiretroviral therapy to achieve viral suppression by the year 2020. We examine
      the first of these targets, focusing on sub-Saharan Africa, the region of the
      world most affected by HIV, to measure the proportion of PLHIV estimated to know
      their HIV status, and to identify background and behavioral characteristics
      significantly associated with gaps in ever testing among PLHIV. METHODS AND
      FINDINGS: We analyze cross-sectional population-based data from the Demographic
      and Health Surveys (DHS) and AIDS Indicator Surveys (AIS) fielded since 2010 in
      16 sub-Saharan African countries where voluntary serological testing was recently
      conducted: Burkina Faso, Cameroon, Chad, Cote d'Ivoire, Ethiopia, Gabon, Lesotho,
      Malawi, Namibia, Rwanda, Sierra Leone, Tanzania, Togo, Uganda, Zambia, and
      Zimbabwe. Survey response rates averaged 95.0% (range 89.3-99.5%), while consent
      to serotesting averaged 94.9% (range 88.7-99.6%). This study, which includes more
      than 14,000 respondents living with HIV, finds that 69% of PLHIV in the average
      study country have ever been tested for HIV (range 34-95%). Based on timing of
      the last test and on ART coverage, we estimate that 54% of PLHIV in the average
      country are aware of their status (range 26-84%). Adjusted logistic regression
      finds that men (median adjusted odds ratio [AOR] = 0.38), adults with less than
      primary education (median AOR = 0.31), and adolescents (median AOR = 0.32) are
      consistently less likely to have ever been tested for HIV than women, adults with
      secondary and above education, and adults age 30-39, respectively. In most
      countries unadjusted logistic regression also finds significant gaps in testing
      among the poorest groups and those reporting never having had sex. CONCLUSION:
      The fact that an average of 54% of PLHIV in these 16 countries are estimated to
      know their status reflects encouraging progress. However, not only is this
      average far short of the 90% target set by UNAIDS for 2020, but it also implies
      that in the average study country nearly one-half of PLHIV are unable to access
      lifesaving care and treatment because they are unaware that they are HIV
      positive. Several gaps in HIV testing coverage exist, particularly among
      adolescents, the least educated, and men. While the need to target demographic
      groups at greatest risk of HIV continues, additional interventions focused on
      reaching men and on reaching socially vulnerable populations such as adolescents,
      the poorest, and the least educated are essential.

PMID- 29023511
TI  - A new and improved algorithm for the quantification of chromatin condensation
      from microscopic data shows decreased chromatin condensation in regenerating
      axolotl limb cells.
AB  - The nuclear landscape plays an important role in the regulation of tissue and
      positional specific genes in embryonic and developing cells. Changes in this
      landscape can be dynamic, and are associated with the differentiation of cells
      during embryogenesis, and the de-differentiation of cells during induced
      pluripotent stem cell (iPSC) formation and in many cancers. However, tools to
      quantitatively characterize these changes are limited, especially in the in vivo
      context, where numerous tissue types are present and cells are arranged in
      multiple layers. Previous tools have been optimized for the monolayer nature of
      cultured cells. Therefore, we present a new algorithm to quantify the
      condensation of chromatin in two in vivo systems. We first developed this
      algorithm to quantify changes in chromatin compaction and validated it in
      differentiating spermatids in zebrafish testes. Our algorithm successfully
      detected the typical increase in chromatin compaction as these cells
      differentiate. We then employed the algorithm to quantify the changes that occur
      in amphibian limb cells as they participate in a regenerative response. We
      observed that the chromatin in the limb cells de-compacts as they contribute to
      the regenerating organ. We present this new tool as an open sourced software that
      can be readily accessed and optimized to quantify chromatin compaction in complex
      multi-layered samples.

PMID- 29023513
TI  - Fruits and vegetables consumption and depressive symptoms: A population-based
      study in Peru.
AB  - OBJECTIVES: Among different factors, diet patterns seem to be related to
      depression. The aim of this study was to evaluate the association between the
      consumption of fruits and/or vegetables and depressive symptoms.
      METHODOLOGY/PRINCIPAL FINDINGS: A secondary data analysis was conducted using
      information from a population-based survey from 25 regions from Peru. The outcome
      was the presence of depressive symptoms according to the Patient Health
      Questionnaire (cutoff >=15 to define major depressive syndrome); whereas the
      exposure was the self-reported consumption of fruits and/or vegetables (in
      tertiles and using WHO recommendation >=5 servings/day). The association of
      interest was evaluated using Poisson regression models controlling for the
      complex-sample survey design and potential confounders. Data from 25,901
      participants were analyzed, mean age 44.2 (SD: 17.7) and 13,944 (54.0%) women.
      Only 910 (3.8%; 95%CI: 3.5%-4.2%) individuals reported consuming >=5 servings of
      fruits and/or vegetables/day; whereas 819 (2.8%; 95%CI: 2.5%-3.1%) had depressive
      symptoms. Those in the lowest tertile of fruits and/or vegetables consumption had
      greater prevalence of depressive symptoms (PR = 1.88; 95%CI: 1.39-2.55) than
      those in the highest tertile. This association was stronger with fruits (PR =
      1.92; 95%CI: 1.46-2.53) than vegetables (PR = 1.42; 95%CI: 1.05-1.93) alone.
      CONCLUSIONS: An inverse relationship between consumption of fruits and/or
      vegetables and depressive symptoms is reported. Less than 5% of subjects reported
      consuming the amount of fruits and vegetables recommended by the WHO. There is a
      need to implement strategies to promote better diet patterns with potential
      impact on mental health.

PMID- 29023514
TI  - Prostate cancer screening: Knowledge, attitudes and practices in a sample of men
      in Italy. A survey.
AB  - BACKGROUND: The aim of this study was to evaluate the knowledge, attitudes and
      behaviors towards prostate cancer and its prevention. METHODS: A cross-sectional
      survey was conducted on a random sample of 625 fathers of students attending
      eight public schools. The self-administered questionnaire included questions on:
      socio-demographic characteristics, personal and familiar medical history of
      prostate cancer, knowledge about prostate cancer and the prostate-specific
      antigen (PSA) test, perception of risk towards prostate cancer, perception of the
      benefits of having a PSA-test, willingness to receive the PSA-test and sources of
      and needs of information regarding prostate cancer and the PSA-test. RESULTS:
      72.7% of respondents had heard about the PSA-test and 51.1% of those had heard
      about it through their physicians. This knowledge was higher: in men with older
      age, in those that had a higher level of education, in those who had a relative
      with prostrate problems or prostate cancer and in those with prostate problems.
      Perceived personal risk of contracting prostate cancer was associated with a
      higher level of education, in those who had received information about prostate
      cancer from a physician and in those with prostate problems. Only 29.6% of men
      had undergone a PSA-test and 59.4% were willing to do so in the future. The
      significant predictors of the willingness to receive a PSA-test were the belief
      that the PSA-test was useful, the perception of not very good personal health
      status, and need of additional information about the PSA-test. CONCLUSION:
      Respondents have a moderate knowledge about prostate cancer and a good propensity
      to undergo the PSA-test. Therefore, it would be necessary to increase information
      on the risks of prostate cancer and the benefits of prostate cancer prevention.

PMID- 29023512
TI  - The ultrastructural characteristics of porcine hepatocytes donated after cardiac
      death and preserved with warm machine perfusion preservation.
AB  - The effects of warm machine perfusion preservation of liver grafts donated after
      cardiac death on the intracellular three-dimensional ultrastructure of the
      organelles in hepatocytes remain unclear. Here we analyzed comparatively the
      ultrastructure of the endomembrane systems in porcine hepatocytes under warm
      ischemia and successive hypothermic and midthermic machine perfusion
      preservation, a type of the warm machine perfusion. Porcine liver grafts which
      had a warm ischemia time of 60 minutes were perfused for 4 hours with modified
      University of Wisconsin gluconate solution. Group A grafts were preserved with
      hypothermic machine perfusion preservation at 8 degrees C constantly for 4 hours.
      Group B grafts were preserved with rewarming up to 22 degrees C by warm machine
      perfusion preservation for 4 hours. An analysis of hepatocytes after 60 minutes
      of warm ischemia by scanning electron microscope revealed the appearance of
      abnormal vacuoles and invagination of mitochondria. In the hepatocytes preserved
      by subsequent hypothermic machine perfusion preservation, strongly swollen
      mitochondria were observed. In contrast, the warm machine perfusion preservation
      could preserve the functional appearance of mitochondria in hepatocytes.
      Furthermore, abundant vacuoles and membranous structures sequestrating cellular
      organelles like autophagic vacuoles were frequently observed in hepatocytes after
      warm machine perfusion preservation. In conclusion, the ultrastructure of the
      endomembrane systems in the hepatocytes of liver grafts changed in accordance
      with the temperature conditions of machine perfusion preservation. In addition,
      temperature condition of the machine perfusion preservation may also affect the
      condition of the hepatic graft attributed to autophagy systems, and consequently
      alleviate the damage of the hepatocytes.

PMID- 29023515
TI  - A novel bacteriocin from Enterococcus faecalis 478 exhibits a potent activity
      against vancomycin-resistant enterococci.
AB  - The emergence of multidrug-resistant enterococci (MDRE) and particularly
      vancomycin-resistant enterococci (VRE) is considered a serious health problem
      worldwide, causing the need for new antimicrobials. The aim of this study was to
      discover and characterize bacteriocin against clinical isolates of MDRE and VRE.
      Over 10,000 bacterial isolates from water, environment and clinical samples were
      screened. E. faecalis strain 478 isolated from human feces produced the highest
      antibacterial activity against several MDRE and VRE strains. The optimum
      condition for bacteriocin production was cultivation in MRS broth at 37 degrees
      C, pH 5-6 for 16 hours. The bacteriocin-like substance produced from E. faecalis
      strain EF478 was stable at 60 degrees C for at least 1 hour and retained its
      antimicrobial activity after storage at -20 degrees C for 1 year, at 4 degrees C
      for 6 months, and at 25 degrees C for 2 months. A nano-HPLC electrospray
      ionization multi-stage tandem mass spectrometry (nLC-ESI-MS/MS) analysis showed
      that the amino acid sequences of the bacteriocin-like substance was similar to
      serine protease of E. faecalis, gi|488296663 (NCBI database), which has never
      been reported as a bacteriocin. This study reported a novel bacteriocin with high
      antibacterial activity against VRE and MDRE.

PMID- 29023516
TI  - Hypothalamic control systems show differential gene expression during spontaneous
      daily torpor and fasting-induced torpor in the Djungarian hamster (Phodopus
      sungorus).
AB  - Djungarian hamsters are able to use spontaneous daily torpor (SDT) during the
      winter season as well as fasting-induced torpor (FIT) at any time of the year to
      cope with energetically challenging environmental conditions. Torpor is a state
      of severely reduced metabolism with a pronounced decrease in body temperature,
      which enables animals to decrease their individual energy requirements. Despite
      sharing common characteristics, such as reduced body mass before first torpor
      expression and depressed metabolism and body temperature during the torpid state,
      FIT and SDT differ in several physiological properties including torpor bout
      duration, minimal body temperature, fuel utilization and circadian organization.
      It remains unclear, whether SDT and FIT reflect the same phenomenon or two
      different physiological states. The hypothalamus has been suggested to play a key
      role in regulating energy balance and torpor. To uncover differences in molecular
      control mechanisms of torpor expression, we set out to investigate hypothalamic
      gene expression profiles of genes related to orexigenic (Agrp/Npy), circadian
      clock (Bmal1/Per1) and thyroid hormone (Dio2/Mct8) systems of animals undergoing
      SDT and FIT during different torpor stages. Orexigenic genes were mainly
      regulated during FIT and remained largely unaffected by SDT. Expression patterns
      of clock genes showed disturbed circadian clock rhythmicity in animals undergoing
      FIT, but not in animals undergoing SDT. During both, SDT and FIT, decreased Dio2
      expression was detected, indicating reduced hypothalamic T3 availability in both
      types of torpor. Taken together, our results provide evidence that SDT and FIT
      also differ in certain central control mechanisms and support the observation
      that animals undergoing SDT are in energetical balance, whereas animals
      undergoing FIT display a negative energy balance. This should be carefully taken
      into account when interpreting data in torpor research, especially from animal
      models of fasting-induced hypometabolism such as mice.

PMID- 29023517
TI  - Developmental delay in the Amazon: The social determinants and prevalence among
      rural communities in Peru.
AB  - The consequences of poor child development are becoming increasingly recognized.
      Programs are being put in place around the world to improve child development by
      providing healthy and stimulating environments for children. However, these
      programs often have limited reach and little is known about the prevalence of
      developmental delay in under-developed communities. The current study set-out to
      better understand the prevalence of developmental delay in rural communities in
      the Amazon region of Peru. Also, it explores social determinants that are
      associated with any delay. Cross-sectional study by evaluating developmental
      delay in children under 4 years utilizing Ages and Stages Questionnaire (ASQ-3).
      Additionally, conducting a social determinants questionnaire answered by
      caretakers to identify social drivers for developmental delay. The data was
      analyzed with multi-variant analysis to measure association. The prevalence of
      developmental delay in the Amazonian communities was 26.7% (19.3% in
      communication, 11.4% in gross motor skills, 8% in both) (N = 596). The
      multivariate logistic regression analysis revealed significant associations
      between developmental delay and; level of education (OR 0.64, p = 0.009), age of
      mother during child's birth (OR 0.96, p = 0.002), visits by community health
      agents (OR 0.73, p = 0.013), and river as primary water source (OR 2.39, p =
      0.001). The social determinants questionnaire revealed that 39% of the mothers
      had their first child before the age of 17, nearly half stopped going to school
      before the age of 12 (52%), 29% gave birth at home, 13% breast fed for less than
      7 months, and 50% of the children had diarrhea in the last month. There is still
      a great need to improve the conditions for child development in the Amazon region
      of Peru. One-fourth of the children suffer from developmental delay, which will
      likely impede their potentials for life unless something is done. The impact of
      education, age of mother at birth of the child, community health agents, and
      access to clean drinking water were important findings. Improvements can be made
      in these areas to create a large, cost-effective impact on the well-being of the
      communities.

PMID- 29023519
TI  - Essential Annotation Schema for Ecology (EASE)-A framework supporting the
      efficient data annotation and faceted navigation in ecology.
AB  - Ecology has become a data intensive science over the last decades which often
      relies on the reuse of data in cross-experimental analyses. However, finding data
      which qualifies for the reuse in a specific context can be challenging. It
      requires good quality metadata and annotations as well as efficient search
      strategies. To date, full text search (often on the metadata only) is the most
      widely used search strategy although it is known to be inaccurate. Faceted
      navigation is providing a filter mechanism which is based on fine granular
      metadata, categorizing search objects along numeric and categorical parameters
      relevant for their discovery. Selecting from these parameters during a full text
      search creates a system of filters which allows to refine and improve the results
      towards more relevance. We developed a framework for the efficient annotation and
      faceted navigation in ecology. It consists of an XML schema for storing the
      annotation of search objects and is accompanied by a vocabulary focused on
      ecology to support the annotation process. The framework consolidates ideas which
      originate from widely accepted metadata standards, textbooks, scientific
      literature, and vocabularies as well as from expert knowledge contributed by
      researchers from ecology and adjacent disciplines.

PMID- 29023518
TI  - Factors associated with the risk of gingival disease in patients with rheumatoid
      arthritis.
AB  - Gingival disase and rheumatoid arthritis (RA) are linked at both the
      epidemiologic and pathogenesis levels. In this study, we aimed to identify
      environmental factors associated with RA and gingival disease and to investigate
      factors that protect the gingival tissue in RA patients. This retrospective study
      analyzed 754 RA patients with gingival disease selected from the NHANES database
      who completed the mobile examination center interview/examination between 1999
      and 2004. Data collected included demographics, lifestyle, dietary intake, and
      biomarkers. The study included 173 RA patients with gingival disease.
      Multivariate logistic regression analysis showed that the odds of gingival
      disease were significantly increased with male gender. However, the odds of
      gingival disease was significantly decreased with increased vitamin C intake (OR
      = 0.996, p = 0.041), and higher serum vitamin D levels (OR = 0.979, p = 0.011).
      Given the significant association between the prevalence of gingival disease and
      RA, identification of risk factors of gingival disease will be useful as a
      screening tool in national health surveys to improve the management of
      periodontal disease in patients with RA.

PMID- 29023520
TI  - DNA accumulation on ventilation system filters in university buildings in
      Singapore.
AB  - INTRODUCTION: Biological particles deposit on air handling system filters as they
      process air. This study reports and interprets abundance and diversity
      information regarding biomass accumulation on ordinarily used filters acquired
      from several locations in a university environment. METHODS: DNA-based analysis
      was applied both to quantify (via DNA fluorometry and qPCR) and to characterize
      (via high-throughput sequencing) the microbial material on filters, which mainly
      processed recirculated indoor air. Results were interpreted in relation to
      building occupancy and ventilation system operational parameters. RESULTS: Based
      on accumulated biomass, average DNA concentrations per AHU filter surface area
      across nine indoor locations after twelve weeks of filter use were in the
      respective ranges 1.1 to 41 ng per cm2 for total DNA, 0.02 to 3.3 ng per cm2 for
      bacterial DNA and 0.2 to 2.0 ng DNA per cm2 for fungal DNA. The most abundant
      genera detected on the AHU filter samples were Clostridium, Streptophyta,
      Bacillus, Acinetobacter and Ktedonobacter for bacteria and Aspergillus,
      Cladosporium, Nigrospora, Rigidoporus and Lentinus for fungi. Conditional indoor
      airborne DNA concentrations (median (range)) were estimated to be 13 (2.6-107)
      pg/m3 for total DNA, 0.4 (0.05-8.4) pg/m3 for bacterial DNA and 2.3 (1.0-5.1)
      pg/m3 for fungal DNA. CONCLUSION: Conditional airborne concentrations and the
      relative abundances of selected groups of genera correlate well with occupancy
      level. Bacterial DNA was found to be more responsive than fungal DNA to
      differences in occupancy level and indoor environmental conditions.

PMID- 29023521
TI  - Factors affecting eye drop instillation in glaucoma patients with visual field
      defect.
AB  - BACKGROUND: To investigate the success rate of eye drop instillation in glaucoma
      patients with visual field defect as well as non-glaucoma volunteers. Factors
      that may affect the success rate of eye drop instillation were also evaluated.
      DESIGN: A prospective, observational study. PARTICIPANTS: Seventy-eight glaucoma
      patients and 85 non-glaucoma volunteers were recruited in this study. METHODS:
      Open angle glaucoma patients with visual field defect as well as non-glaucoma
      volunteers were asked to video record their procedures of eye drop instillation
      using a 5-mL plastic bottle of artificial tear solution. Success of eye drop
      instillation was judged on video based on the first one drop of solution
      successfully applied on the cornea, by two investigators. MAIN OUTCOME MEASURES:
      Success rate of eye drop instillation in glaucoma patients and non-glaucoma
      volunteers. Factors related to success rate of eye drop instillation, such as
      visual field defect and clinical characteristics, were also analyzed using
      multivariable logistic regression. RESULTS: No significant deference in mean age
      was observed between two groups (glaucoma: 64.5 +/- 14.4 years, non-glaucoma:
      60.9 +/- 14.1 years, P = 0.1156). Success rate of eye drop instillation was
      significantly lower (P = 0.0215) in glaucoma patients (30/78; 38.5%) than in non
      glaucoma volunteers (48/85; 56.5%). The most frequent reason of instillation
      failure in glaucoma patients was touching the bulbar conjunctiva, cornea, eyelid
      or eyelashes with the tip of the bottle (29.5%). Multivariable logistic
      regression analysis identified lower corrected visual acuity (VA) (<= 1.0; odds
      ratio [OR] = 0.20, 95% confidence interval [CI] 0.04-0.93, P = 0.0411), lower
      mean deviation (MD) (< -12 dB; OR = 0.20, 95% CI 0.05-0.86, P = 0.0307) and
      visual field defect (VFD) in the inferior hemifield (OR = 0.11, 95% CI 0.02-0.34,
      P < 0.001) to be significantly related to instillation failure in glaucoma
      patients. CONCLUSIONS: Success rate of eye drop instillation was significantly
      lower in glaucoma patients than in non-glaucoma volunteers. Corrected VA <= 1.0,
      MD < -12 dB and/or VFD in the inferior hemifield may be related to failure of eye
      drop instillation.

PMID- 29023522
TI  - Microencapsulation of Clostridium difficile specific bacteriophages using
      microfluidic glass capillary devices for colon delivery using pH triggered
      release.
AB  - The prevalence of pathogenic bacteria acquiring multidrug antibiotic resistance
      is a global health threat to mankind. This has motivated a renewed interest in
      developing alternatives to conventional antibiotics including bacteriophages
      (viruses) as therapeutic agents. The bacterium Clostridium difficile causes colon
      infection and is particularly difficult to treat with existing antibiotics; phage
      therapy may offer a viable alternative. The punitive environment within the
      gastrointestinal tract can inactivate orally delivered phages. C. difficile
      specific bacteriophage, myovirus CDKM9 was encapsulated in a pH responsive
      polymer (Eudragit(r) S100 with and without alginate) using a flow focussing glass
      microcapillary device. Highly monodispersed core-shell microparticles containing
      phages trapped within the particle core were produced by in situ polymer curing
      using 4-aminobenzoic acid dissolved in the oil phase. The size of the generated
      microparticles could be precisely controlled in the range 80 MUm to 160 MUm
      through design of the microfluidic device geometry and by varying flow rates of
      the dispersed and continuous phase. In contrast to free 'naked' phages, those
      encapsulated within the microparticles could withstand a 3 h exposure to
      simulated gastric fluid at pH 2 and then underwent a subsequent pH triggered
      burst release at pH 7. The significance of our research is in demonstrating that
      C. difficile specific phage can be formulated and encapsulated in highly uniform
      pH responsive microparticles using a microfluidic system. The microparticles were
      shown to afford significant protection to the encapsulated phage upon prolonged
      exposure to an acid solution mimicking the human stomach environment. Phage
      encapsulation and subsequent release kinetics revealed that the microparticles
      prepared using Eudragit(r) S100 formulations possess pH responsive
      characteristics with phage release triggered in an intestinal pH range suitable
      for therapeutic purposes. The results reported here provide proof-of-concept data
      supporting the suitability of our approach for colon targeted delivery of phages
      for therapeutic purposes.

PMID- 29023524
TI  - Polymorphism IL-1RN rs419598 reduces the susceptibility to generalized
      periodontitis in a population of European descent.
AB  - Interleukin (IL) 1-ra is a potent endogenous competitive inhibitor of IL-alpha
      and beta and has an anti-inflammatory role. Study objectives were: 1) to assess
      the associations of IL-1RN genetic single nucleotide polymorphism (SNP)
      (rs419598) with generalized chronic periodontitis (GCP), generalized aggressive
      periodontitis (GAgP), and absence of periodontitis and 2) to assess its
      association with the load of five periodontopathogenic bacteria and periodontal
      clinical variables. A cross-sectional analytic study was conducted in 123
      patients with GCP, 60 patients with GAgP, and 20 controls. Reverse hybridization
      PCR was used for genotyping analysis to detect SNPs in IL-1A (rs1800587), IL-1B
      (rs1143634), and IL-1RN (rs419598) genes and for determination of the load of
      five periodontopathogenic bacteria. The severity and extension of periodontitis
      were assessed. Multinomial logistic regression and mediated regression analyses
      were performed. Considering results for GCP and GAgP patients together, the
      presence of polymorphism in IL-1A and/or IL-1B gene was associated with a higher
      likelihood of periodontitis, (OR = 8.11; 95%CI [1.85-35.48]), but this likelihood
      was reduced when IL-1RN polymorphism was also present, (OR = 5.91; 95%CI [1.08
      32.27]). IL-1RN polymorphism was significantly associated with lower counts of
      red complex bacteria, specifically Porphyromona gingivalis, Tannerella forsythia,
      and Prevotella intermedia, which were associated with improved clinical outcomes.
      The polymorphic expression of IL-1RN (rs419598) gene may be associated with a
      reduced susceptibility to GAgP and GCP in populations of European descent. This
      effect may be mediated by a decreased load of Porphyromona gingivalis, Tannerella
      forsythia, and Prevotella intermedia.

PMID- 29023523
TI  - The role of glutamate in neuronal ion homeostasis: A case study of spreading
      depolarization.
AB  - Simultaneous changes in ion concentrations, glutamate, and cell volume together
      with exchange of matter between cell network and vasculature are ubiquitous in
      numerous brain pathologies. A complete understanding of pathological conditions
      as well as normal brain function, therefore, hinges on elucidating the molecular
      and cellular pathways involved in these mostly interdependent variations. In this
      paper, we develop the first computational framework that combines the Hodgkin
      Huxley type spiking dynamics, dynamic ion concentrations and glutamate
      homeostasis, neuronal and astroglial volume changes, and ion exchange with
      vasculature into a comprehensive model to elucidate the role of glutamate uptake
      in the dynamics of spreading depolarization (SD)-the electrophysiological event
      underlying numerous pathologies including migraine, ischemic stroke, aneurysmal
      subarachnoid hemorrhage, intracerebral hematoma, and trauma. We are particularly
      interested in investigating the role of glutamate in the duration and termination
      of SD caused by K+ perfusion and oxygen-glucose deprivation. Our results
      demonstrate that glutamate signaling plays a key role in the dynamics of SD, and
      that impaired glutamate uptake leads to recovery failure of neurons from SD. We
      confirm predictions from our model experimentally by showing that inhibiting
      astrocytic glutamate uptake using TFB-TBOA nearly quadruples the duration of SD
      in layers 2-3 of visual cortical slices from juvenile rats. The model equations
      are either derived purely from first physical principles of electroneutrality,
      osmosis, and conservation of particles or a combination of these principles and
      known physiological facts. Accordingly, we claim that our approach can be used as
      a future guide to investigate the role of glutamate, ion concentrations, and
      dynamics cell volume in other brain pathologies and normal brain function.

PMID- 29023525
TI  - Multisensory emotion perception in congenitally, early, and late deaf CI users.
AB  - Emotions are commonly recognized by combining auditory and visual signals (i.e.,
      vocal and facial expressions). Yet it is unknown whether the ability to link
      emotional signals across modalities depends on early experience with audio-visual
      stimuli. In the present study, we investigated the role of auditory experience at
      different stages of development for auditory, visual, and multisensory emotion
      recognition abilities in three groups of adolescent and adult cochlear implant
      (CI) users. CI users had a different deafness onset and were compared to three
      groups of age- and gender-matched hearing control participants. We hypothesized
      that congenitally deaf (CD) but not early deaf (ED) and late deaf (LD) CI users
      would show reduced multisensory interactions and a higher visual dominance in
      emotion perception than their hearing controls. The CD (n = 7), ED (deafness
      onset: <3 years of age; n = 7), and LD (deafness onset: >3 years; n = 13) CI
      users and the control participants performed an emotion recognition task with
      auditory, visual, and audio-visual emotionally congruent and incongruent nonsense
      speech stimuli. In different blocks, participants judged either the vocal (Voice
      task) or the facial expressions (Face task). In the Voice task, all three CI
      groups performed overall less efficiently than their respective controls and
      experienced higher interference from incongruent facial information. Furthermore,
      the ED CI users benefitted more than their controls from congruent faces and the
      CD CI users showed an analogous trend. In the Face task, recognition efficiency
      of the CI users and controls did not differ. Our results suggest that CI users
      acquire multisensory interactions to some degree, even after congenital deafness.
      When judging affective prosody they appear impaired and more strongly biased by
      concurrent facial information than typically hearing individuals. We speculate
      that limitations inherent to the CI contribute to these group differences.

PMID- 29023526
TI  - Antithrombotic therapy strategies for atrial fibrillation patients undergoing
      percutaneous coronary intervention: A systematic review and network meta
      analysis.
AB  - OBJECTIVE: The aim of this systematic review and network meta-analysis was to
      evaluate the comparative efficacy and safety of antiplatelet agents, vitamin K
      antagonist (VKA) and non-VKA oral anticoagulants (NOACs) in patients with atrial
      fibrillation (AF) undergoing percutaneous coronary intervention (PCI). METHODS:
      PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were
      searched to identify clinical trials comparing antiplatelet drugs with VKA and
      NOACs or their combination in AF patients undergoing PCI with a mean/median
      follow-up of at least 12 months. A network meta-analysis was conducted to
      directly and indirectly compare the efficacy and safety of competitive
      antithrombotic regimens with a Bayesian random-effects model. Results were
      presented as relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: A
      total of 15 studies enrolling 13,104 patients were included. Among 5 regimens,
      rivaroxaban 15 mg daily plus P2Y12 inhibitor treatment demonstrated significant
      superiority over dual- and triple-antiplatelet therapies (DAPT, TT) in reducing
      thromboembolic events (0.64 [0.38, 0.95] and 0.68 [0.43, 0.98], respectively) but
      showed the maximum possibility of major bleeding risk, while VKA plus single
      antiplatelet therapy (SAPT) seemed the safest. Significantly less risk of major
      bleeding was seen in DAPT group than that in TT group (0.63 [0.39, 0.99]).
      CONCLUSIONS: The present study suggests that combination of VKA and SAPT is the
      best choice for AF patients undergoing PCI considering both efficacy and safety.
      Rivaroxaban 2.5 mg twice daily plus DAPT treatment owns the highest probability
      to be the optimal alternative to VKA plus SAPT for these patients.

PMID- 29023527
TI  - Dose-escalated radiotherapy for unresectable or locally recurrent pancreatic
      cancer: Dose volume analysis, toxicity and outcome of 28 consecutive patients.
AB  - PURPOSE: The role of radiotherapy for unresectable pancreatic cancer is
      controversial. A benefit of additional radiotherapy is supported by some
      observations. A dose-effect relationship was recently found by dose escalation
      employing image guided and intensity modulated radiotherapy. METHODS: We
      retrospectively evaluated 28 consecutive patients, all with history of extensive
      prior therapies for unresectable locally advanced/ recurrent pancreatic cancer
      (LAPC/LRPC). Treatment was delivered by helical tomotherapy after daily position
      verification with computed tomography. Dose to the planned target volume (PTV)
      was 51 Gy, while the dose to the macroscopic tumor was escalated by a
      simultaneous integrated boost to a median cumulative dose of 66 Gy (60-66 Gy).
      Concomitant chemotherapy consisted mainly of capecitabine (n = 23). RESULTS: 10
      of 28 patients presented acute toxicities > grade 2, one patient succumbed to
      gastrointestinal bleeding after treatment. No correlations of toxicities and dose
      volume histograms (DVH) of retrospectively delineated small bowel loops were
      observed, although average small bowel volume receiving >= 20 Gy was 374 ml. DVH
      analyses revealed a correlation of splenic parameters and acute toxicity:
      Vomiting, anorexia, dehydration, hematologic toxicity, fatigue, combined gastro
      intestinal toxicity wit R-values between 0.392 and 0.561 (all p-values > 0.05).
      Only one patient developed late toxicities > grade 2. With an average follow-up
      time in surviving patients of 14 months median overall survival time was 19
      months and median time to local recurrence 13 months. In 8 patients with
      available imaging of local recurrence: 5 in field recurrences, 2 marginal
      recurrences and one lymph node recurrence outside the high dose radiation field
      were observed. In univariate analysis only DeltaCA-19-9 during radiotherapy was
      associated with local control (p = 0.029) and overall survival (p = 0.049).
      CONCLUSION: Dose escalated normo-fractionated radiotherapy for LAPC/LRPC seems
      feasible and suitable to prolong local control and in consequence long-term
      survival. However, in-field local progression is still frequently observed and
      possibilities to increase the local effectiveness should be evaluated. Exposure
      of the spleen was predictive for acute toxicity and should be further
      investigated.

PMID- 29023529
TI  - Radiographic measurement of the quadriceps angle in dogs.
AB  - The direction of the force of the quadriceps muscle group is expressed by the
      value of the quadriceps angle, between the long axis of the muscle rectus femoris
      and the patellar ligament. This value is often modified in dogs with patellar
      luxation, a common orthopaedic disease of the stifle joint in both small and
      large dogs. The aims of the present study were to give a reference value for the
      quadriceps angle in healthy small and medium-large breed dogs. The medical
      records of healthy dogs and their pelvic limb radiographs (2014-2016) were
      reviewed. The radiographs were then divided into two groups: Group A (small dogs
      <15 kg body weight) and Group B (medium-large dogs >15 kg). The quadriceps angle
      of each pelvic limb was assessed using a digital software program in order to
      compare values between the two groups. The radiographs of 160 dogs, 80 per group
      were studied along with the assessment of the 320 pelvic limbs. The median
      quadriceps angle values obtained were in contrast with the literature: in Group
      A, it was 18.3 degrees  and, in Group B, it was 8.7 degrees ; moreover, the
      quadriceps angle value for Group A was statistically higher than for Group B
      (p<0.0001). No significant difference was present between males and females, or
      between right and left hindlimbs. In Group B, the Labrador Retriever breed
      influenced the quadriceps angle (p = 0.0005). The outcome of this survey provides
      an objective parameter, or additional information, to explain the different
      quadriceps mechanisms of small and medium-large dogs. In future studies the QA
      range values assessed in the two size groups may be useful in defining the
      magnitude of the malalignment of the extensor mechanism in both healthy dogs and
      ones with patellar luxation.

PMID- 29023528
TI  - Evaluation of gastrointestinal bacterial population for the production of
      holocellulose enzymes for biomass deconstruction.
AB  - The gastrointestinal (GI) habitat of ruminant and non-ruminant animals sustains a
      vast ensemble of microbes that are capable of utilizing lignocellulosic plant
      biomass. In this study, an indigenous swine (Zovawk) and a domesticated goat
      (Black Bengal) were investigated to isolate bacteria having plant biomass
      degrading enzymes. After screening and enzymatic quantification of eighty-one
      obtained bacterial isolates, Serratia rubidaea strain DBT4 and Aneurinibacillus
      aneurinilyticus strain DBT87 were revealed as the most potent strains, showing
      both cellulase and xylanase production. A biomass utilization study showed that
      submerged fermentation (SmF) of D2 (alkaline pretreated pulpy biomass) using
      strain DBT4 resulted in the most efficient biomass deconstruction with maximum
      xylanase (11.98 U/mL) and FPase (0.5 U/mL) activities (55 degrees C, pH 8). The
      present study demonstrated that bacterial strains residing in the
      gastrointestinal region of non-ruminant swine are a promising source for
      lignocellulose degrading microorganisms that could be used for biomass
      conversion.

PMID- 29023531
TI  - Correction: Drivers of abundance and spatial distribution of reef-associated
      sharks in an isolated atoll reef system.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0177374.].

PMID- 29023530
TI  - Allele-specific expression at the androgen receptor alpha gene in a hybrid
      unisexual fish, the Amazon molly (Poecilia formosa).
AB  - The all-female Amazon molly (Poecilia formosa) is the result of a hybridization
      of the Atlantic molly (P. mexicana) and the sailfin molly (P. latipinna)
      approximately 120,000 years ago. As a gynogenetic species, P. formosa needs to
      copulate with heterospecific males including males from one of its bisexual
      ancestral species. However, the sperm only triggers embryogenesis of the diploid
      eggs. The genetic information of the sperm donor typically will not contribute to
      the next generation of P. formosa. Hence, P. formosa possesses generally one
      allele from each of its ancestral species at any genetic locus. This raises the
      question whether both ancestral alleles are equally expressed in P. formosa.
      Allele-specific expression (ASE) has been previously assessed in various
      organisms, e.g., human and fish, and ASE was found to be important in the context
      of phenotypic variability and disease. In this study, we utilized Real-Time PCR
      techniques to estimate ASE of the androgen receptor alpha (aralpha) gene in
      several distinct tissues of Amazon mollies. We found an allelic bias favoring the
      maternal ancestor (P. mexicana) allele in ovarian tissue. This allelic bias was
      not observed in the gill or the brain tissue. Sequencing of the promoter regions
      of both alleles revealed an association between an Indel in a known CpG island
      and differential expression. Future studies may reveal whether our observed cis
      regulatory divergence is caused by an ovary-specific trans-regulatory element,
      preferentially activating the allele of the maternal ancestor.

PMID- 29023532
TI  - Risk factors for gallstones and kidney stones in a cohort of patients with
      inflammatory bowel diseases.
AB  - BACKGROUND: Gallstones and kidney stones are known complications of inflammatory
      bowel diseases (IBD). Risk factors have been insufficiently studied and
      explanatory studies date back up to 30 years. It remains unclear, whether
      improved treatment options also influenced risk factors for these complications.
      OBJECTIVES: Identifying risk factors for gallstones and kidney stones in IBD
      patients. METHODS: Using data from the Swiss Inflammatory Bowel Disease Cohort
      Study we assessed associations of diseases characteristics with gallstones and
      kidney stones in univariate and multivariate logistic regression analyses.
      RESULTS: Out of 2323 IBD patients, 104 (7.8%) Crohn's disease (CD) and 38 (3.8%)
      ulcerative colitis (UC) patients were diagnosed with gallstones. Significant risk
      factors for gallstones were diagnosis of CD, age at diagnosis, disease activity
      and duration, NSAID intake, extra-intestinal manifestations and intestinal
      surgery. Kidney stones were described in 61 (4.6%) CD and 30 (3.0%) UC patients.
      Male gender, disease activity, intestinal surgery, NSAID usage and reduced
      physical activity were significant risk factors. Hospitalization was associated
      with gallstones and kidney stones. The presence of gallstones increased the risk
      for kidney stones (OR 4.87, p<0.001). CONCLUSION: The diagnosis of CD, intestinal
      surgery, prolonged NSAID use, disease activity and duration and bowel stenosis
      were significantly associated with cholecystonephrolithiasis in IBD.

PMID- 29023533
TI  - Circadian rhythms in parasites.

PMID- 29023534
TI  - BeWith: A Between-Within method to discover relationships between cancer modules
      via integrated analysis of mutual exclusivity, co-occurrence and functional
      interactions.
AB  - The analysis of the mutational landscape of cancer, including mutual exclusivity
      and co-occurrence of mutations, has been instrumental in studying the disease. We
      hypothesized that exploring the interplay between co-occurrence, mutual
      exclusivity, and functional interactions between genes will further improve our
      understanding of the disease and help to uncover new relations between cancer
      driving genes and pathways. To this end, we designed a general framework, BeWith,
      for identifying modules with different combinations of mutation and interaction
      patterns. We focused on three different settings of the BeWith schema: (i) BeME
      WithFun, in which the relations between modules are enriched with mutual
      exclusivity, while genes within each module are functionally related; (ii) BeME
      WithCo, which combines mutual exclusivity between modules with co-occurrence
      within modules; and (iii) BeCo-WithMEFun, which ensures co-occurrence between
      modules, while the within module relations combine mutual exclusivity and
      functional interactions. We formulated the BeWith framework using Integer Linear
      Programming (ILP), enabling us to find optimally scoring sets of modules. Our
      results demonstrate the utility of BeWith in providing novel information about
      mutational patterns, driver genes, and pathways. In particular, BeME-WithFun
      helped identify functionally coherent modules that might be relevant for cancer
      progression. In addition to finding previously well-known drivers, the identified
      modules pointed to other novel findings such as the interaction between NCOR2 and
      NCOA3 in breast cancer. Additionally, an application of the BeME-WithCo setting
      revealed that gene groups differ with respect to their vulnerability to different
      mutagenic processes, and helped us to uncover pairs of genes with potentially
      synergistic effects, including a potential synergy between mutations in TP53 and
      the metastasis related DCC gene. Overall, BeWith not only helped us uncover
      relations between potential driver genes and pathways, but also provided
      additional insights on patterns of the mutational landscape, going beyond cancer
      driving mutations. Implementation is available at
      https://www.ncbi.nlm.nih.gov/CBBresearch/Przytycka/software/bewith.html.

PMID- 29023535
TI  - Effect of protein and carbohydrate solutions on running performance and cognitive
      function in female recreational runners.
AB  - This study compared the effects of a carbohydrate-electrolyte-protein solution
      (CEPS, 2% protein plus 4% carbohydrate), carbohydrate-electrolyte solution (CES,
      6% carbohydrate), and noncaloric sweetened placebo (PLA) on both 21-km running
      performance and cognitive function. Eleven female recreational endurance runners
      performed a 21-km time-trial running on three occasions, separated by at least 28
      days. In a randomized cross-over design, they ingested CEPS, CES, or PLA at a
      rate of 150 mL every 2.5 km with no time feedback. A cognitive function test was
      performed before and after the run. Participants ingested approximately 24 g/h
      carbohydrate plus 12 g/h protein in CEPS trial, and 36 g/h carbohydrate in CES
      trial during each 21-km trial. Time to complete the time-trial was slightly
      shorter (P < 0.05) during CES (129.6 +/- 8.8 min) than PLA (134.6 +/- 11.5 min),
      with no differences between CEPS and the other two trials. The CEPS trial showed
      higher composite of visual motor speed than the PLA trial (P < 0.05). In
      conclusion, CES feedings might improve 21-km time-trial performance in female
      recreational runners compared with a PLA. However, adding protein to the CES
      provided no additional time-trial performance benefit. CEPS feeding during
      prolonged exercise could benefit visual motor speed compared to PLA alone, but no
      differences in the performance of the other cognitive function tests were found.

PMID- 29023537
TI  - Development and validation of a nursing professionalism evaluation model in a
      career ladder system.
AB  - BACKGROUND: The clinical ladder system categorizes the degree of nursing
      professionalism and rewards and is an important human resource tool for managing
      nursing. AIM: We developed a model to evaluate nursing professionalism, which
      determines the clinical ladder system levels, and verified its validity. METHODS:
      Data were collected using a clinical competence tool developed in this study, and
      existing methods such as the nursing professionalism evaluation tool, peer
      reviews, and face-to-face interviews to evaluate promotions and verify the
      presented content in a medical institution. Reliability and convergent and
      discriminant validity of the clinical competence evaluation tool were verified
      using SmartPLS software. The validity of the model for evaluating overall nursing
      professionalism was also analyzed. RESULTS: Clinical competence was determined by
      five dimensions of nursing practice: scientific, technical, ethical, aesthetic,
      and existential. The structural model explained 66% of the variance. Clinical
      competence scales, peer reviews, and face-to-face interviews directly determined
      nursing professionalism levels. CONCLUSIONS: The evaluation system can be used
      for evaluating nurses' professionalism in actual medical institutions from a
      nursing practice perspective. IMPLICATIONS FOR NURSING MANAGEMENT: A conceptual
      framework for establishing a human resources management system for nurses and a
      tool for evaluating nursing professionalism at medical institutions is provided.

PMID- 29023538
TI  - Correction: Metabolomics analysis: Finding out metabolic building blocks.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0177031.].

PMID- 29023536
TI  - Change in inflammatory parameters in prefrail and frail persons obtaining
      physical training and nutritional support provided by lay volunteers: A
      randomized controlled trial.
AB  - The aim of the study was to compare the effects of home visits with physical
      training and nutritional support on inflammatory parameters to home visits with
      social support alone within a randomized controlled trial. Prefrail and frail
      persons received home visits from lay volunteers twice a week for 12 weeks.
      Participants in the physical training and nutritional intervention group (PTN, n
      = 35) conducted two sets of six strength exercises and received nutritional
      support. The social support group (SoSu, n = 23) received visits only. TNF-alpha,
      IL-6, CRP, and total leukocyte count were assessed at baseline and after 12
      weeks. Changes over time within groups were analyzed with paired t-tests;
      differences between groups were analyzed with ANCOVA for repeated measurements.
      In the PTN group, IL-6 and CRP remained stable, whereas in the SoSu group, IL-6
      increased significantly from a median value of 2.6 pg/l (min-max = 2.0-10.2) to
      3.0 pg/l (min-max = 2.0-20.8), and CRP rose from 0.2 mg/dl (min-max = 0.1-0.9) to
      0.3 mg/dl (min-max = 0.1-3.0) after 12 weeks. In CRP, a significant difference
      between groups was found. TNF-alpha and total leukocyte count did not change in
      either the PTN group or the SoSu group. Persons showing an increase in physical
      performance (OR 4.54; 95% CI = 1.33-15.45) were more likely to have constant or
      decreased IL-6 values than persons who showed no improvement. In conclusion, in
      non-robust older adults, a physical training and nutritional support program
      provided by lay volunteers can delay a further increase in some inflammatory
      parameters.

PMID- 29023539
TI  - Despite disorganized synapse structure, Th2 cells maintain directional delivery
      of CD40L to antigen-presenting B cells.
AB  - Upon recognition of peptide displayed on MHC molecules, Th1 and Th2 cells form
      distinct immunological synapse structures. Th1 cells have a bull's eye synapse
      structure with TCR/ MHC-peptide interactions occurring central to a ring of
      adhesion molecules, while Th2 cells have a multifocal synapse with small clusters
      of TCR/MHC interactions throughout the area of T cell/antigen-presenting cell
      interaction. In this study, we investigated whether this structural difference in
      the immunological synapse affects delivery of T cell help. The immunological
      synapse is thought to ensure antigen-specific delivery of cytolytic granules and
      killing of target cells by NK cells and cytolytic T cells. In helper T cells, it
      has been proposed that the immunological synapse may direct delivery of other
      effector molecules including cytokines. CD40 ligand (CD40L) is a membrane-bound
      cytokine essential for antigen-specific T cell help for B cells in the antibody
      response. We incubated Th1 and Th2 cells overnight with a mixture of antigen
      presenting and bystander B cells, and the delivery of CD40L to B cells and
      subsequent B cell responses were compared. Despite distinct immunological synapse
      structures, Th1 and Th2 cell do not differ in their ability to deliver CD40L and
      T cell help in an antigen-specific fashion, or in their susceptibility to
      inhibition of help by a blocking anti-CD40L antibody.

PMID- 29023540
TI  - Emotional and tangible social support in a German population-based sample:
      Development and validation of the Brief Social Support Scale (BS6).
AB  - Aim of the study was the development and validation of the psychometric
      properties of a six-item bi-factorial instrument for the assessment of social
      support (emotional and tangible support) with a population-based sample. A cross
      sectional data set of N = 15,010 participants enrolled in the Gutenberg Health
      Study (GHS) in 2007-2012 was divided in two sub-samples. The GHS is a population
      based, prospective, observational single-center cohort study in the Rhein-Main
      Region in western Mid-Germany. The first sub-sample was used for scale
      development by performing an exploratory factor analysis. In order to test
      construct validity, confirmatory factor analyses were run to compare the
      extracted bi-factorial model with the one-factor solution. Reliability of the
      scales was indicated by calculating internal consistency. External validity was
      tested by investigating demographic characteristics health behavior, and distress
      using analysis of variance, Spearman and Pearson correlation analysis, and
      logistic regression analysis. Based on an exploratory factor analysis, a set of
      six items was extracted representing two independent factors. The two-factor
      structure of the Brief Social Support Scale (BS6) was confirmed by the results of
      the confirmatory factor analyses. Fit indices of the bi-factorial model were good
      and better compared to the one-factor solution. External validity was
      demonstrated for the BS6. The BS6 is a reliable and valid short scale that can be
      applied in social surveys due to its brevity to assess emotional and practical
      dimensions of social support.

PMID- 29023541
TI  - Improved influenza viral vector based Brucella abortus vaccine induces robust B
      and T-cell responses and protection against Brucella melitensis infection in
      pregnant sheep and goats.
AB  - We previously developed a potent candidate vaccine against bovine brucellosis
      caused by Brucella abortus using the influenza viral vector expressing Brucella
      Omp16 and L7/L12 proteins (Flu-BA). Our success in the Flu-BA vaccine trial in
      cattle and results of a pilot study in non-pregnant small ruminants prompted us
      in the current study to test its efficacy against B. melitensis infection in
      pregnant sheep and goats. In this study, we improved the Flu-BA vaccine
      formulation and immunization method to achieve maximum efficacy and safety. The
      Flu-BA vaccine formulation had two additional proteins Omp19 and SOD, and
      administered thrice with 20% Montanide Gel01 adjuvant, simultaneously by both
      subcutaneous and conjunctival routes at 21 days intervals in pregnant sheep and
      goats. At 42 days post-vaccination (DPV) we detected antigen-specific IgG
      antibodies predominantly of IgG2a isotype but also IgG1, and also detected a
      strong lymphocyte recall response with IFN-gamma production. Importantly, our
      candidate vaccine prevented abortion in 66.7% and 77.8% of pregnant sheep and
      goats, respectively. Furthermore, complete protection (absence of live B.
      melitensis 16M) was observed in 55.6% and 66.7% of challenged sheep and goats,
      and 72.7% and 90.0% of their fetuses (lambs/yeanlings), respectively. The
      severity of B. melitensis 16M infection in vaccinated sheep and goats and their
      fetuses (index of infection and rates of Brucella colonization in tissues) was
      significantly lower than in control groups. None of the protection parameters
      after vaccination with Flu-BA vaccine were statistically inferior to protection
      seen with the commercial B. melitensis Rev.1 vaccine (protection against abortion
      and vaccination efficacy, alpha = 0.18-0.34, infection index, P = 0.37-0.77,
      Brucella colonization, P = 0.16 to P > 0.99). In conclusion, our improved Flu-BA
      vaccine formulation and delivery method were found safe and effective in
      protecting pregnant sheep and goats against adverse consequences of B. melitensis
      infection.

PMID- 29023542
TI  - Massachusetts Medicaid members that smoked in 2008: Characteristics associated
      with smoking status in 2014.
AB  - The smoking rate among non-elderly Medicaid enrollees is more than double the
      rate for those privately insured; smoking-related conditions account for 15% of
      Medicaid expenditures. Under state health reform, Massachusetts Medicaid
      (MassHealth) made tobacco cessation treatment available beginning in 2006. We
      used surveys conducted in 2008 and 2014 to examine changes in smoking abstinence
      rates among MassHealth members identified as smokers and to identify factors
      associated with being a former smoker. Members previously identified as smokers
      were surveyed by mail or phone; 2008 and 2014 samples included 3,116 and 2,971
      members, respectively. Surveys collected demographic and health information,
      asked members whether they smoked cigarettes "every day, some days or not at
      all', and asked questions to assess smoking intensity among current smokers. The
      2014 survey included an open ended-question asking members "what helped the most"
      in quitting or quit attempts. We observed a significant decrease in members
      reporting smoking "every/some days" of 15.5 percentage points (p < .0001) from
      2008 to 2014, and a significant decrease in smokers reporting smoking "more than
      10 cigarettes on days smoked" of 16.7 percentage points (p < .0001). Compared to
      smokers, former smokers more frequently reported health concerns, the influence
      of family members, and the use of e-cigarettes as helping the most in quitting.
      Expanded access to tobacco cessation treatment under the Affordable Care Act may
      have help to reduce the high smoking rates among Medicaid enrollees.
      Additionally, smokers' concerns about health and the influence of family and
      friends provide opportunities for targeted intervention and messaging about
      quitting.

PMID- 29023543
TI  - A mannitol/sorbitol receptor stimulates dietary intake in Tribolium castaneum.
AB  - In insects, perception of chemical stimuli is involved in the acceptance or
      rejection of food. Gustatory receptors (Grs) that regulate external signals in
      chemosensory organs have been found in many insects. Tribolium castaneum, a major
      pest of stored products, possesses over 200 Gr genes. An expanded repertoire of
      Gr genes appears to be required for diet recognition in species that are
      generalist feeders; however, it remains unclear whether T. castaneum recognizes a
      suite of chemicals common to many products or whether its feeding is activated by
      specific chemicals, and whether its Grs are involved in feeding behavior. It is
      difficult to determine the food preferences of T. castaneum based on dietary
      intake due to a lack of appropriate methodology. This study established a novel
      dietary intake estimation method using gypsum, designated the TribUTE (Tribolium
      Urges To Eat) assay. For this assay, T. castaneum adults were fed a gypsum block
      without added organic compounds. Sweet preference was determined by adding
      sweeteners and measuring the amount of gypsum in the excreta. Mannitol was the
      strongest activator of T. castaneum dietary intake. In a Xenopus oocyte
      expression, TcGr20 was found to be responsible for mannitol and sorbitol
      responses, but not for responses to other tested non-volatile compounds. The EC50
      values of TcGr20 for mannitol and sorbitol were 72.6 mM and 90.6 mM,
      respectively, suggesting that TcGr20 is a feasible receptor for the recognition
      of mannitol at lower concentrations. We used RNAi and the TribUTE assay to
      examine whether TcGr20 expression was involved in mannitol recognition. The
      amounts of excreta in TcGr20 dsRNA-injected adults decreased significantly,
      despite the presence of mannitol, compared to control adults. Taken together, our
      results indicate that T. castaneum adults recognized mannitol/sorbitol using the
      TcGr20 receptor, thereby facilitating the dietary intake of these compounds.

PMID- 29023544
TI  - Radar based technology for non-contact monitoring of accumulation of blood in the
      head: A numerical study.
AB  - BACKGROUND: This theoretical study examines the use of radar to continuously
      monitor "accumulation of blood in the head" (ACBH) non-invasively and from a
      distance, after the location of a hematoma or hemorrhage in the brain was
      initially identified with conventional medical imaging. Current clinical practice
      is to monitor ABCH with multiple, subsequent, conventional medical imaging. The
      radar technology introduced in this study could provide a lower cost and safe
      alternative to multiple conventional medical imaging monitoring for ACBH.
      MATERIALS AND METHODS: The goal of this study is to evaluate the feasibility of
      using radar to monitor changes in blood volume in the brain through a numerical
      simulation of ACBH monitoring from remote, with a directional spiral slot
      antennae, in 3-D models of the brain. The focus of this study is on evaluating
      the effect of frequencies on the antennae reading. To that end we performed the
      calculations for frequencies of 100 MHz, 500 MHz and 1 GHz. RESULTS AND
      DISCUSSION: The analysis shows that the ACBH can be monitored with radar and the
      monitoring resolution improves with an increase in frequency, in the range
      studied. However, it also appears that when typical clinical dimensions of
      hematoma and hemorrhage are used, the variable ratio of blood volume radius and
      radar wavelength can bring the measurements into the Mie and Rayleigh regions of
      the radar cross section. In these regions there is an oscillatory change in
      signal with blood volume size. For some frequencies there is an increase in
      signal with an increase in volume while in others there is a decrease.
      CONCLUSIONS: While radar can be used to monitor ACBH non-invasively and from a
      distance, the observed Mie region dependent oscillatory relation between blood
      volume size and wavelength requires further investigation. Classifiers,
      multifrequency algorithms or ultra-wide band radar are possible solutions that
      should be explored in the future.

PMID- 29023545
TI  - Territorial choruses of giant otter groups (Pteronura brasiliensis) encode
      information on group identity.
AB  - Group living animals often engage in corporate territorial defence. Territorial
      group vocalizations can provide information about group identity, size and
      composition. Neighbouring groups may use this information to avoid unfavourable
      direct conflicts. Giant otters are highly social and territorial animals with an
      elaborate vocal repertoire. They produce long-range screams when they are alert
      or excited, i.e. in an alarm, isolation or begging context. Long-range screams
      are not only produced by one individual at a time ('single screams') but also by
      multiple group members simultaneously, resulting in a highly conspicuous 'group
      chorus'. Wild giant otters regularly produce group choruses during interactions
      with predators, when they detect intruders in their territory or before group
      reunions after separation. Since single screams and especially group choruses
      probably contribute to the groups' corporate territorial defence, we hypothesized
      that group identity is encoded in single screams and group choruses. We analysed
      vocalizations from five wild and three captive giant otter groups and found
      statistical evidence for a group signature in group choruses. Results for single
      screams were less conclusive, which might have been caused by the comparatively
      lower sample size. We suggest that giant otters may gain information on group
      identity by listening to group choruses. Group identity likely constitutes
      important social information for giant otters since territory boundaries of
      neighbouring groups can overlap and direct inter-group conflicts are severe.
      Therefore, group chorusing may contribute to the mutual avoidance of members from
      different groups.

PMID- 29023547
TI  - Correction: Can quartet analyses combining maximum likelihood estimation and
      Hennigian logic overcome long branch attraction in phylogenomic sequence data?
AB  - [This corrects the article DOI: 10.1371/journal.pone.0183393.].

PMID- 29023546
TI  - Steroid hormones and psychological responses to soccer matches: Insights from a
      systematic review and meta-analysis.
AB  - The present systematic review and meta-analysis aimed to assess the perturbations
      in hormonal and psychological homeostasis in response to soccer match-play. These
      perturbations were explored according to match outcome (i.e., win versus loss),
      gender, type of contest (i.e., competitive versus non-competitive fixtures) and
      competitive level (i.e., novice versus high-level). The review was conducted
      according to the Population/Intervention or Exposure/Comparison/Outcome(s) (PICO)
      criteria and the Preferred Reporting Items for Systematic Reviews and Meta
      analyses (PRISMA) guidelines. Match outcome, type of contest and competitive
      levels were moderator variables in the examined steroid hormones responses to a
      soccer match-play. Different testosterone responses were seen between match
      winners (increase) and losers (decrease) when compared to pre-game or baseline
      values (p <0.05), whilst no changes could be detected for cortisol relative to
      match outcome in female soccer players. Males (Delta% = 6.26; ES = 0.28)
      demonstrated a marginally lower increase in testosterone levels when compared to
      females (Delta% = 49.16; ES = 1.00), though not statistically significant.
      Females (Delta% = 162.7; ES = 0.98) did not demonstrate elevated cortisol match
      response compared to males (Delta% = 34.60; ES = 1.20). Male novice soccer match
      play increased cortisol levels compared to high-level soccer match-play (Q =
      18.08, p<0.001). Competitive soccer matches increased cortisol levels compared to
      non-competitive fixtures (i.e., collegiate tournament). Additionally, competitive
      levels moderate the relationship between a soccer match and testosterone levels
      (p <0.001), regardless of gender differences. From the presented systematic
      review and meta-analysis it appears (1) cortisol changes are associated with
      cognitive anxiety in starter female soccer players, while (2) testosterone
      changes are associated with changes in mood state in females and social
      connectedness in male soccer players. This apparent psycho-physiological
      relationship may proffer the opportunity for targeted intervention(s) by
      practitioners to favorably influence performance and/or recovery agendas. Further
      mechanistic and/or applied evidence is required in this regard in addition to
      further data sets from females.

PMID- 29023548
TI  - Comparison of six electromyography acquisition setups on hand movement
      classification tasks.
AB  - Hand prostheses controlled by surface electromyography are promising due to the
      non-invasive approach and the control capabilities offered by machine learning.
      Nevertheless, dexterous prostheses are still scarcely spread due to control
      difficulties, low robustness and often prohibitive costs. Several sEMG
      acquisition setups are now available, ranging in terms of costs between a few
      hundred and several thousand dollars. The objective of this paper is the relative
      comparison of six acquisition setups on an identical hand movement classification
      task, in order to help the researchers to choose the proper acquisition setup for
      their requirements. The acquisition setups are based on four different sEMG
      electrodes (including Otto Bock, Delsys Trigno, Cometa Wave + Dormo ECG and two
      Thalmic Myo armbands) and they were used to record more than 50 hand movements
      from intact subjects with a standardized acquisition protocol. The relative
      performance of the six sEMG acquisition setups is compared on 41 identical hand
      movements with a standardized feature extraction and data analysis pipeline aimed
      at performing hand movement classification. Comparable classification results are
      obtained with three acquisition setups including the Delsys Trigno, the Cometa
      Wave and the affordable setup composed of two Myo armbands. The results suggest
      that practical sEMG tests can be performed even when costs are relevant (e.g. in
      small laboratories, developing countries or use by children). All the presented
      datasets can be used for offline tests and their quality can easily be compared
      as the data sets are publicly available.

PMID- 29023550
TI  - Effects of acute alcohol ingestion on eye movements and cognition: A double
      blind, placebo-controlled study.
AB  - Alcohol is one of the most consumed psychoactive substances in the world, and the
      negative impact related to alcohol use has become a worldwide public health
      issue. Alcohol is able to affect diffusely several areas of the Central Nervous
      System, which could impair visual functions, including eye movements, and
      cognitive processes. The objective of the present study was to investigate the
      effects of moderate alcohol intake in eyes movements, as an indicator of
      cognitive processing underlying the visual search in a the Maze task. We
      investigated the concentration of 0.08% blood alcohol concentration (BAC), using
      an intra-subject, double-blind, and placebo-controlled experimental design with a
      sample size of 20 young adults (11 men and nine women). All volunteers
      participated in both conditions, i.e., alcohol (0.08%) and placebo (0.00%), in a
      counterbalanced order. We use the Tobii TX300 eye tracker to evaluate eye
      movements during completion of Visual Maze Test. The results showed significant
      differences in the following eye movement patterns: the first fixation latency,
      number and duration of fixations (mean and total), the number and duration of
      saccades (mean and total), and the total execution time in the test. In addition,
      we investigate the areas of interest (AOI), decision points in which the
      participant must decide which course to follow. We verified that the participants
      in the alcohol condition had a significantly greater number of fixations in both
      AOI, in comparison to the placebo condition. Overall, our findings confirm that
      moderate doses of alcohol can change the eye movements of young adults. These
      alterations may evidence the influence of alcohol in cognitive processes, such as
      flexibility, attention, and planning, which are required during resolution of
      Maze Task.

PMID- 29023549
TI  - Supraphysiologic control over HIV-1 replication mediated by CD8 T cells
      expressing a re-engineered CD4-based chimeric antigen receptor.
AB  - HIV is adept at avoiding naturally generated T cell responses; therefore, there
      is a need to develop HIV-specific T cells with greater potency for use in HIV
      cure strategies. Starting with a CD4-based chimeric antigen receptor (CAR) that
      was previously used without toxicity in clinical trials, we optimized the vector
      backbone, promoter, HIV targeting moiety, and transmembrane and signaling domains
      to determine which components augmented the ability of T cells to control HIV
      replication. This re-engineered CAR was at least 50-fold more potent in vitro at
      controlling HIV replication than the original CD4 CAR, or a TCR-based approach,
      and substantially better than broadly neutralizing antibody-based CARs. A
      humanized mouse model of HIV infection demonstrated that T cells expressing
      optimized CARs were superior at expanding in response to antigen, protecting CD4
      T cells from infection, and reducing viral loads compared to T cells expressing
      the original, clinical trial CAR. Moreover, in a humanized mouse model of HIV
      treatment, CD4 CAR T cells containing the 4-1BB costimulatory domain controlled
      HIV spread after ART removal better than analogous CAR T cells containing the
      CD28 costimulatory domain. Together, these data indicate that potent HIV-specific
      T cells can be generated using improved CAR design and that CAR T cells could be
      important components of an HIV cure strategy.

PMID- 29023552
TI  - The impact of male burials on the construction of Corded Ware identity:
      Reconstructing networks of information in the 3rd millennium BC.
AB  - The emergence of Corded Ware Groups throughout Europe in the 3rd millennium BC is
      one of the most defining events in European history. From the Wolga to the Rhine
      communities start to speak Indo-European languages and bury their dead in an
      extremely similar fashion. Recent ancient DNA-analyses identify a massive
      migration from the Eurasian steppe as the prime cause for this event. However,
      there is a fundamental difference between expressing a Corded Ware identity-the
      sharing of world views and ideas-and having a specific DNA-profile. Therefore, we
      argue that investigating the exchange of cultural information on burial rites
      between these communities serves as a crucial complement to the exchange of
      biological information. By adopting a practice perspective to 1161 Corded Ware
      burials throughout north-western Europe, combined with similarity indexes and
      network representations, we demonstrate a high degree of information sharing on
      the burial ritual between different regions. Moreover, we show that male burials
      are much more international in character than female burials and as such can be
      considered as the vector along which cultural information and Corded Ware
      identity was transmitted. This finding highlights an underlying complex societal
      organization of Corded Ware burial rites in which gender roles had a significant
      impact on the composition and transmission of cultural information. Our findings
      corroborate recent studies that suggest the Corded Ware was a male focused
      society.

PMID- 29023551
TI  - A multilayered electrospun graft as vascular access for hemodialysis.
AB  - Despite medical achievements, the number of patients with end-stage kidney
      disease keeps steadily raising, thereby entailing a high number of surgical and
      interventional procedures to establish and maintain arteriovenous vascular access
      for hemodialysis. Due to vascular disease, aneurysms or infection, the preferred
      access-an autogenous arteriovenous fistula-is not always available and
      appropriate. Moreover, when replacing small diameter blood vessels, synthetic
      vascular grafts possess well-known disadvantages. A continuous multilayered
      gradient electrospinning was used to produce vascular grafts made of collagen
      type I nanofibers on luminal and adventitial graft side, and poly-E-caprolactone
      as medial layer. Therefore, a custom-made electrospinner with robust
      environmental control was developed. The morphology of electrospun grafts was
      characterized by scanning electron microscopy and measurement of mechanical
      properties. Human microvascular endothelial cells were cultured in the graft
      under static culture conditions and compared to cultures obtained from dynamic
      continuous flow bioreactors. Immunofluorescent analysis showed that endothelial
      cells form a continuous luminal layer and functional characteristics were
      confirmed by uptake of acetylated low-density-lipoprotein. Incorporation of
      vancomycin and gentamicin to the medial graft layer allowed antimicrobial
      inhibition without exhibiting an adverse impact on cell viability. Most striking
      a physiological hemocompatibility was achieved for the multilayered grafts.

PMID- 29023553
TI  - Unearthing the hidden world of roots: Root biomass and architecture differ among
      species within the same guild.
AB  - The potential benefits of planting trees have generated significant interest with
      respect to sequestering carbon and restoring other forest based ecosystem
      services. Reliable estimates of carbon stocks are pivotal for understanding the
      global carbon balance and for promoting initiatives to mitigate CO2 emissions
      through forest management. There are numerous studies employing allometric
      regression models that convert inventory into aboveground biomass (AGB) and
      carbon (C). Yet the majority of allometric regression models do not consider the
      root system nor do these equations provide detail on the architecture and shape
      of different species. The root system is a vital piece toward understanding the
      hidden form and function roots play in carbon accumulation, nutrient and plant
      water uptake, and groundwater infiltration. Work that estimates C in forests as
      well as models that are used to better understand the hydrologic function of
      trees need better characterization of tree roots. We harvested 40 trees of six
      different species, including their roots down to 2 mm in diameter and created
      species-specific and multi-species models to calculate aboveground (AGB), coarse
      root belowground biomass (BGB), and total biomass (TB). We also explore the
      relationship between crown structure and root structure. We found that BGB
      contributes ~27.6% of a tree's TB, lateral roots extend over 1.25 times the
      distance of crown extent, root allocation patterns varied among species, and that
      AGB is a strong predictor of TB. These findings highlight the potential
      importance of including the root system in C estimates and lend important
      insights into the function roots play in water cycling.

PMID- 29023554
TI  - Reproducibility of shear wave elastography (SWE) in patients with chronic liver
      disease.
AB  - The presence of significant fibrosis is an indicator for liver disease staging
      and prognosis. The aim of the study was to determine reproducibility of real-time
      shear wave elastography using a hepatic biopsy as the reference standard to
      identify patients with chronic liver disease. Forty patients with chronic liver
      disease and 12 normal subjects received shear wave elastography performed by
      skilled operators. Interoperator reproducibility was studied in 29 patients.
      Fibrosis was evaluated using the Metavir score. The median and range shear wave
      elastography values in chronic liver disease subjects were 6.15 kPa and 3.14-16.7
      kPa and were 4.49 kPa and 2.92-7.32 kPa in normal subjects, respectively. With
      respect to fibrosis detected by liver biopsy, shear wave elastography did not
      change significantly between F0 and F1 (p = 0.334), F1 and F2 (p = 0.611), or F3
      and F4 (0.327); a significant difference was observed between the F0-F2 and F3-F4
      groups (p = 0.002). SWE also correlated with inflammatory activity (Rs = 0.443, p
      = 0.0023) and ALT levels (Rs = 0.287, p = 0.0804). Age, sex and body mass index
      did not affect shear wave elastography measurements. Using receiver operator
      characteristic curves, two threshold values for shear wave elastography were
      identified: 5.62 kPa for patients with fibrosis (>=F2; sensitivity 80%,
      specificity 69.4%, and accuracy 77%) and 7.04 kPa for patients with severe
      fibrosis (>=F3; sensitivity 88.9%, specificity 81%, and accuracy 89%). Overall
      interobserver agreement was excellent and was analysed using an interclass
      correlation coefficient (0.94; CI 0.87-0.97).This study shows that shear wave
      elastography executed by skilled operators can be performed on almost all chronic
      liver disease patients with high reproducibility. It is not influenced by age,
      sex or body mass index, identifies severely fibrotic patients and is also related
      to inflammatory activity.

PMID- 29023555
TI  - Assessing the individual risk of fecal poliovirus shedding among vaccinated and
      non-vaccinated subjects following national health weeks in Mexico.
AB  - BACKGROUND: Mexico introduced inactivated polio vaccine (IPV) into its routine
      immunization (RI) schedule in 2007 but continued to give trivalent oral polio
      vaccine (tOPV) twice a year during national health weeks (NHW) through 2015.
      OBJECTIVES: To evaluate individual variables associated with poliovirus (PV)
      shedding among children with IPV-induced immunity after vaccination with tOPV and
      their household contacts. MATERIALS AND METHODS: We recruited 72 children (both
      genders, <=30 months, vaccinated with at least two doses of IPV) and 144
      household contacts (both genders, 2 per household, children and adults) between
      08/2010 and 09/2010 in Orizaba, Veracruz. Three NHW took place (one before and
      two after enrollment). We collected fecal samples monthly for 12 months, and
      tested 2500 samples for polioviruses types 1, 2 and 3 with three serotype
      specific singleplex real-time RT-PCR (rRT-PCR) assays. In order to increase the
      specificity for OPV virus, all positive and 112 negative samples were also
      processed with a two-step, OPV serotype-specific multiplex rRT-PCR. ANALYSIS: We
      estimated adjusted hazard ratios (HR) and 95% CI using Cox proportional hazards
      regression for recurrent events models accounting for individual clustering to
      assess the association of individual variables with the shedding of any
      poliovirus for all participants and stratifying according to whether the
      participant had received tOPV in the month of sample collection. RESULTS: 216
      participants were included. Of the 2500 collected samples, using the singleplex
      rRT-PCR assay, PV was detected in 5.7% (n = 142); PV1 in 1.2% (n = 29), PV2 in
      4.1% (n = 103), and PV3 in 1.9% (n = 48). Of the 256 samples processed by
      multiplex rRT-PCR, PV was detected in 106 (PV1 in 16.41% (n = 42), PV2 in 21.09%
      (n = 54), and PV3 in 23.05% (n = 59). Both using singleplex and multiplex assays,
      shedding of OPV among non-vaccinated children and subjects older than 5 years of
      age living in the same household was associated with shedding of PV2 by a
      household contact. All models were adjusted by sex, age, IPV vaccination and OPV
      shedding by the same individual during the previous month of sample collection.
      CONCLUSION: Our results provide important evidence regarding the circulation of
      poliovirus in a mixed vaccination context (IPV+OPV) which mimics the
      "transitional phase" that occurs when countries use both vaccines simultaneously.
      Shedding of OPV2 by household contacts was most likely the source of infection of
      non-vaccinated children and subjects older than 5 years of age living in the same
      household.

PMID- 29023556
TI  - Lumbar spinal canal MRI diameter is smaller in herniated disc cauda equina
      syndrome patients.
AB  - INTRODUCTION: Correlation between magnetic resonance imaging (MRI) and clinical
      features in cauda equina syndrome (CES) is unknown; nor is known whether there
      are differences in MRI spinal canal size between lumbar herniated disc patients
      with CES versus lumbar herniated discs patients without CES, operated for
      sciatica. The aims of this study are 1) evaluating the association of MRI
      features with clinical presentation and outcome of CES and 2) comparing lumbar
      spinal canal diameters of lumbar herniated disc patients with CES versus lumbar
      herniated disc patients without CES, operated because of sciatica. METHODS: MRIs
      of CES patients were assessed for the following features: level of disc lesion,
      type (uni- or bilateral) and severity of caudal compression. Pre- and
      postoperative clinical features (micturition dysfunction, defecation dysfunction,
      altered sensation of the saddle area) were retrieved from the medical files. In
      addition, anteroposterior (AP) lumbar spinal canal diameters of CES patients were
      measured at MRI. AP diameters of lumbar herniated disc patients without CES,
      operated for sciatica, were measured for comparison. RESULTS: 48 CES patients
      were included. At MRI, bilateral compression was seen in 82%; complete caudal
      compression in 29%. MRI features were not associated with clinical presentation
      nor outcome. AP diameter was measured for 26 CES patients and for 31 lumbar
      herniated disc patients without CES, operated for sciatica. Comparison displayed
      a significant smaller AP diameter of the lumbar spinal canal in CES patients
      (largest p = 0.002). Compared to average diameters in literature, diameters of
      CES patients were significantly more often below average than that of the
      sciatica patients (largest p = 0.021). CONCLUSION: This is the first study
      demonstrating differences in lumbar spinal canal size between lumbar herniated
      disc patients with CES and lumbar herniated disc patients without CES, operated
      for sciatica. This finding might imply that lumbar herniated disc patients with a
      relative small lumbar spinal canal might need to be approached differently in
      managing complaints of herniated disc. Since the number of studied patients is
      relatively small, further research should be conducted before clinical
      consequences are considered.

PMID- 29023558
TI  - Correction: Glycoside Hydrolase MoGls2 Controls Asexual/Sexual Development, Cell
      Wall Integrity and Infectious Growth in the Rice Blast Fungus.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0162243.].

PMID- 29023557
TI  - STARD 2015 was reproducible in a large set of studies on glaucoma.
AB  - AIM: To investigate the reproducibility of the updated Standards for the
      Reporting of Diagnostic Accuracy Studies tool (STARD 2015) in a set of 106
      studies included in a Cochrane diagnostic test accuracy (DTA) systematic review
      of imaging tests for diagnosing manifest glaucoma. METHODS: One senior rater with
      DTA methodological and clinical expertise used STARD 2015 on all studies, and
      each of three raters with different training profiles assessed about a third of
      the studies. RESULTS: Raw agreement was very good or almost perfect between the
      senior rater and an ophthalmology resident with DTA methods training, acceptable
      with a clinical rater with little DTA methods training, and only moderate with a
      pharmacology researcher with general, but not DTA, systematic review training and
      no clinical expertise. The relationship between adherence with STARD 2015 and
      methodological quality with QUADAS 2 was only partial and difficult to
      investigate, suggesting that raters used substantial context knowledge in risk of
      bias assessment. CONCLUSIONS: STARD 2015 proved to be reproducible in this
      specific research field, provided that both clinical and DTA methodological
      expertise are achieved through training of its users.

PMID- 29023559
TI  - The relationship between orexin levels and blood pressure changes in patients
      with narcolepsy.
AB  - STUDY OBJECTIVE: Narcolepsy type 1 (NT1) is caused by a deficiency or absence of
      the neurotransmitter orexin. NT1 is also associated with a reduced nocturnal
      "dipping" of blood pressure (BP). The study objective was to analyze whether
      nocturnal BP values differed in patients depleted of orexin, versus those in whom
      production was preserved. METHODS: We performed a retrospective analysis of the
      polysomnographic recordings, orexin levels, and BP values of patients with NT1.
      Data was collected from a total of 21 patients, divided into two groups as
      follows: those with a complete depletion of orexin (n = 11) (Group1), and those
      with a remaining, limited presence of orexin (n = 10) (Group 2). RESULTS: The
      groups did not differ in terms of the clinical features of NT1 or sleep
      characteristics, with an exception of increased number of cataplexy episodes and
      increased percentage of sleep stage 2 in the Group 1. Daytime and nocturnal BP
      did not differ between the groups. Most patients, regardless of group, had a non
      dipping blood pressure pattern, and no difference in dipping prevalence was
      observed between groups. The amplitude of the daytime to nighttime change in BP
      did not differ between the groups. CONCLUSIONS: Non-dipping BP patterns are
      frequent among patients with narcolepsy type 1, but we saw no evidence that they
      depended on whether orexin levels were above or below the assay detection
      threshold. Therefore, our results do not support the hypothesis that in patients
      with narcolepsy type 1 residual orexin levels play a role in the control of
      nocturnal BP dipping.

PMID- 29023560
TI  - Effects of fire frequency on litter decomposition as mediated by changes to
      litter chemistry and soil environmental conditions.
AB  - Litter quality and soil environmental conditions are well-studied drivers
      influencing decomposition rates, but the role played by disturbance legacy, such
      as fire history, in mediating these drivers is not well understood. Fire history
      may impact decomposition directly, through changes in soil conditions that impact
      microbial function, or indirectly, through shifts in plant community composition
      and litter chemistry. Here, we compared early-stage decomposition rates across
      longleaf pine forest blocks managed with varying fire frequencies (annual burns,
      triennial burns, fire-suppression). Using a reciprocal transplant design, we
      examined how litter chemistry and soil characteristics independently and jointly
      influenced litter decomposition. We found that both litter chemistry and soil
      environmental conditions influenced decomposition rates, but only the former was
      affected by historical fire frequency. Litter from annually burned sites had
      higher nitrogen content than litter from triennially burned and fire suppression
      sites, but this was correlated with only a modest increase in decomposition
      rates. Soil environmental conditions had a larger impact on decomposition than
      litter chemistry. Across the landscape, decomposition differed more along soil
      moisture gradients than across fire management regimes. These findings suggest
      that fire frequency has a limited effect on litter decomposition in this
      ecosystem, and encourage extending current decomposition frameworks into
      disturbed systems. However, litter from different species lost different masses
      due to fire, suggesting that fire may impact decomposition through the
      preferential combustion of some litter types. Overall, our findings also
      emphasize the important role of spatial variability in soil environmental
      conditions, which may be tied to fire frequency across large spatial scales, in
      driving decomposition rates in this system.

PMID- 29023562
TI  - Efficacy of chemical disinfectants for the containment of the salamander chytrid
      fungus Batrachochytrium salamandrivorans.
AB  - The recently emerged chytrid fungus Batrachochytrium salamandrivorans (Bsal)
      causes European salamander declines. Proper hygiene protocols including
      disinfection procedures are crucial to prevent disease transmission. Here, the
      efficacy of chemical disinfectants in killing Bsal was evaluated. At all tested
      conditions, Biocidal(r), Chloramine-T(r), Dettol medical(r), Disolol(r), ethanol,
      F10(r), Hibiscrub(r), potassium permanganate, Safe4(r), sodium hypochlorite, and
      Virkon S(r), were effective at killing Bsal. Concentrations of 5% sodium chloride
      or lower, 0.01% peracetic acid and 0.001-1% copper sulphate were inactive against
      Bsal. None of the conditions tested for hydrogen peroxide affected Bsal
      viability, while it did kill Batrachochytrium dendrobatidis (Bd). For Bsal,
      enzymatic breakdown of hydrogen peroxide by catalases and specific morphological
      features (clustering of sporangia, development of new sporangia within the
      original sporangium), were identified as fungal factors altering susceptibility
      to several of the disinfectants tested. Based on the in vitro results we
      recommend 1% Virkon S(r), 4% sodium hypochlorite and 70% ethanol for disinfecting
      equipment in the field, lab or captive setting, with a minimal contact time of 5
      minutes for 1% Virkon S(r) and 1 minute for the latter disinfectants. These
      conditions not only efficiently target Bsal, but also Bd and Ranavirus.

PMID- 29023561
TI  - Expression patterns and promoter analyses of aluminum-responsive NAC genes
      suggest a possible growth regulation of rice mediated by aluminum, hormones and
      NAC transcription factors.
AB  - In acid soils, the solubilized form of aluminum, Al+3, decreases root growth and
      affects the development of most crops. However, like other toxic elements, Al can
      have hormetic effects on plant metabolism. Rice (Oryza sativa) is one of the most
      tolerant species to Al toxicity, and when this element is supplied at low doses,
      growth stimulation has been observed, which could be due to combined mechanisms
      that are partly triggered by NAC transcription factors. This protein family can
      regulate vital processes in plants, including growth, development, and response
      to environmental stimuli, whether biotic or abiotic. Under our experimental
      conditions, 200 MUM Al stimulated root growth and the formation of tillers; it
      also caused differential expression of a set of NAC genes. The promoter regions
      of the genes regulated by Al were analyzed and the cis-acting elements that are
      potentially involved in the responses to different stimuli, including
      environmental stress, were identified. Through the Genevestigator platform, data
      on the expression of NAC genes were obtained by experimental condition, tissue,
      and vegetative stage. This is the first study on NAC genes where in vivo and in
      silico data are complementarily analyzed, relating the hormetic effect of Al on
      plant growth and gene expression with a possible interaction in the response to
      phytohormones in rice. These findings could help to elucidate the possible
      convergence between the signaling pathways mediated by phytohormones and the role
      of the NAC transcription factors in the regulation of growth mediated by low Al
      doses.

PMID- 29023563
TI  - Influence of platinum harmonized textile on neuromuscular, systemic and
      subjective recovery.
AB  - The clothing manufacturer Venex Life-Science tracks the strategy to enhance
      recovery process through implementing platinum harmonized technology (PHT) into
      their Venex(r) Regeneration Wear. The proposed mechanisms of the regeneration
      wear are an increase of parasympathetic activity and an increase of the
      temperature due far-infrared radiation. The purpose of this study was to
      investigate potential effects of Venex regeneration wear on the recovery of
      neuromuscular, systemic and subjective parameters following exercise. In a
      randomized, single-blinded cross-over design, 13 strength-trained male
      participants performed two exercise sessions in one day. After the first exercise
      session and for 3 nights following the exercise day participants wore the Venex
      regeneration wear or a placebo product. Measures of isometric maximum voluntary
      contraction (MVC), voluntary activation (VA) and potentiated twitch torque (PTT)
      of the knee extensors, as well as maximum jump height during the Counter-Movement
      and Drop Jump, creatinkinase (CK) and subjective parameters (perceived pain,
      recovery condition and sleep quality) were obtained before and after each
      exercise session and 24, 48, and 72 hours after the first exercise session. MVC,
      PTT, CK and jump parameters changed over time during the exercise day as well as
      on the following days, however, there were no significant differences between
      treatments. Subjective parameters showed strong effect sizes (i. e. Cohen's d >
      0.6) in favor for Venex but no significant differences between treatments. Based
      on these findings, it is concluded that wearing a platinum harmonized textile
      following exercise did not improve neuromuscular and systemic recovery in a
      trained male population to a statistical noticeable extent. However, the findings
      for the subjective parameters suggest some potential for enhanced recovery that
      requires further research.

PMID- 29023564
TI  - Large (>=3cm) thyroid nodules with benign cytology: Can Thyroid Imaging Reporting
      and Data System (TIRADS) help predict false-negative cytology?
AB  - BACKGROUND: There is controversy about the accuracy of the fine-needle aspiration
      (FNA) cytology results in large sized thyroid nodules. Our aim was to evaluate
      the false-negative rate of FNA for large thyroid nodules and the usefulness of
      the Thyroid Imaging Reporting and Data System (TIRADS) in predicting false
      negative cytology for large thyroid nodules with benign cytology. METHODS: 632
      thyroid nodules larger than or equal to 3cm in size with subsequent benign
      cytology on US-guided FNA were included. US features of internal composition,
      echogenicity, margin, calcifications, and shape were evaluated, and nodules were
      classified according to TIRADS. TIRADS category 3 included nodules without any of
      the following suspicious features:solidity, hypoechogenicity or marked
      hypoechogenicity, microlobulated or irregular margins, microcalcifications, and
      taller-than-wide shape. Category 4a, 4b, 4c, and 5 were assigned to nodules
      showing one, two, three or four, or five suspicious US features, respectively. US
      features associated with malignancy for these lesions were analyzed and
      malignancy risk according to TIRADS was calculated. RESULTS: Of the 632 lesions,
      23 lesions(3.6%) were malignant and 609(96.4%) were benign, suggesting a 3.6%
      false-negative rate for FNA cytology. Of the 23 malignant lesions, final
      pathology was mainly follicular carcinoma minimally invasive(65.2%, 15/23) and
      the follicular variant of papillary carcinoma(26.1%, 6/23). The malignancy risks
      of categories 3, 4a, 4b, and 4c nodules were 0.9%, 4.6%, 10.0%, and 11.8%,
      respectively. CONCLUSION: Large thyroid nodules with benign cytology had a
      relatively high false-negative risk of 3.6% and TIRADS was helpful in predicting
      false-negative cytology for these lesions.

PMID- 29023565
TI  - Urbanity as a determinant of exposure to grass pollen in Helsinki Metropolitan
      area, Finland.
AB  - Little is known about the levels of exposure to grass pollen in urban
      environments. We assessed the spatio-temporal variation of grass pollen
      concentrations and the role of urbanity as a determinant of grass pollen exposure
      in the Helsinki Metropolitan area. We monitored grass pollen concentrations in
      2013 at 16 sites during the peak pollen season by using rotorod-type samplers at
      the breathing height. The sites were in the cities of Helsinki and Espoo,
      Finland, and formed city-specific lines that represented urban-rural gradient.
      The monitoring sites were both visually and based on land use data ranked as high
      to low (graded 1 to 8) pollen area. The lowest grass pollen concentrations were
      observed in the most urban sites compared to the least urban sites (mean 3.6 vs.
      6.8 grains/m3 in Helsinki; P<0.0001, and 5.2 vs. 87.5 grains/m3 in Espoo;
      P<0.0001). Significant differences were observed between concentrations measured
      in morning periods compared to afternoon periods (4.9 vs. 5.4 in Helsinki, P =
      0.0186, and 21.8 vs. 67.1 in Espoo, P = 0.0004). The mean pollen concentration
      increased with decreasing urbanity both in Helsinki (0.59 grains/m3 per urbanity
      rank, 95% CI 0.25-0.93) and Espoo (8.42, 6.23-10.61). Pollen concentrations were
      highest in the afternoons and they were related to the ambient temperature.
      Urbanity was a strong and significant determinant of pollen exposure in two
      Finnish cities. Pollen exposure can periodically reach such high levels even in
      the most urban environments that can cause allergic reactions among individuals
      with allergies.

PMID- 29023566
TI  - Cardiac leiomodin2 binds to the sides of actin filaments and regulates the ATPase
      activity of myosin.
AB  - Leiomodin proteins are vertebrate homologues of tropomodulin, having a role in
      the assembly and maintenance of muscle thin filaments. Leiomodin2 contains an N
      terminal tropomodulin homolog fragment including tropomyosin-, and actin-binding
      sites, and a C-terminal Wiskott-Aldrich syndrome homology 2 actin-binding domain.
      The cardiac leiomodin2 isoform associates to the pointed end of actin filaments,
      where it supports the lengthening of thin filaments and competes with
      tropomodulin. It was recently found that cardiac leiomodin2 can localise also
      along the length of sarcomeric actin filaments. While the activities of
      leiomodin2 related to pointed end binding are relatively well described, the
      potential side binding activity and its functional consequences are less well
      understood. To better understand the biological functions of leiomodin2, in the
      present work we analysed the structural features and the activities of Rattus
      norvegicus cardiac leiomodin2 in actin dynamics by spectroscopic and high-speed
      sedimentation approaches. By monitoring the fluorescence parameters of leiomodin2
      tryptophan residues we found that it possesses flexible, intrinsically disordered
      regions. Leiomodin2 accelerates the polymerisation of actin in an ionic strength
      dependent manner, which relies on its N-terminal regions. Importantly, we
      demonstrate that leiomodin2 binds to the sides of actin filaments and induces
      structural alterations in actin filaments. Upon its interaction with the
      filaments leiomodin2 decreases the actin-activated Mg2+-ATPase activity of
      skeletal muscle myosin. These observations suggest that through its binding to
      side of actin filaments and its effect on myosin activity leiomodin2 has more
      functions in muscle cells than it was indicated in previous studies.

PMID- 29023567
TI  - Carbapenem-resistant Enterobacteriaceae colonization (CRE) and subsequent risk of
      infection and 90-day mortality in critically ill patients, an observational
      study.
AB  - BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as an
      urgent public health threat. Intestinal colonization with CRE has been identified
      as a risk factor for the development of systemic CRE infection, but has not been
      compared to colonization with third and/or fourth generation cephalosporin
      resistant (Ceph-R) Enterobacteriaceae. Moreover, the risk conferred by
      colonization on adverse outcomes is less clear, particularly in critically ill
      patients admitted to the intensive care unit (ICU). METHODS: We carried out a
      cohort study of consecutive adult patients screened for rectal colonization with
      CRE or Ceph-R upon ICU entry between April and July 2013. We identified clinical
      variables and assessed the relationship between CRE or Ceph-R colonization and
      subsequent systemic CRE infection within 30 days (primary outcome) and all-cause
      mortality within 90 days (secondary outcome). RESULTS: Among 338 ICU patients, 94
      (28%) were colonized with either Ceph-R or CRE. 26 patients developed CRE
      infection within 30 days of swab collection; 47% (N = 17/36) of CRE-colonized and
      3% (N = 2/58) of Ceph-R colonized patients. 36% (N = 13/36) of CRE-colonized
      patients died within 90 days compared to 31% (N = 18/58) of Ceph-R-colonized and
      15% (N = 37/244) of non-colonized patients. In a multivariable analysis, CRE
      colonization independently predicted development of a systemic CRE infection at
      30 days (aOR 10.8, 95% CI2.8-41.9, p = 0.0006); Ceph-R colonization did not (aOR
      0.5, 95% CI0.1-3.3, p = 0.5). CRE colonization was associated with increased 90
      day mortality in a univariable analysis (p-value 0.001), in a multivariable
      model, previous hospitalization and medical ICU admission were independent
      predictors of 90-day mortality whereas CRE colonization approached significance
      (aOR 2.3, 95% CI1.0-5.3, p = 0.056). CONCLUSIONS: Our study highlights the
      increased risk of CRE infection and mortality in patients with CRE colonization
      at the time of ICU admission. Future studies are needed to assess how CRE
      colonization can guide empiric antibiotic choices and to develop novel
      decolonization strategies.

PMID- 29023568
TI  - Demonstrating the reliability of transdiagnostic mHealth Routine Outcome
      Monitoring in mental health services using experience sampling technology.
AB  - BACKGROUND: Routine Outcome Monitoring (ROM) should provide a dynamic, within
      treatment forward feedback loop to guide individual treatment decisions across
      diagnostic categories. It has been suggested that the Experience Sampling Method
      (ESM), capturing the film of daily life adaptive processes, offers a flexible,
      personalised and transdiagnostic feedback system for monitoring and adapting
      treatment strategies. This is the first study that uses an ESM application (the
      PsyMateTM) as a routine mobile-ROM (mROM) tool in an ambulatory mental health
      setting. OBJECTIVE: To demonstrate adequate psychometric properties of the
      PsyMateTM app assessing both symptom severity levels as well as daily life
      functioning. METHOD: In a transdiagnostic sample of 64 outpatients, an mROM
      protocol (ESM for 6 days, at 10 semi-random moments a day) and a standard ROM
      instrument (HADS) were administered at baseline and at three-month follow-up. We
      measured positive affect (PA), negative affect (NA), quality of sleep, positive
      social interaction, activity-related stress, tiredness, and feeling unwell.
      RESULTS: Subjects completed 53% of the measurements at baseline (N = 64) and 48%
      at follow-up (N = 29). Factor analysis and subsequent reliability analysis of PA
      and NA confirmed the two constructs. Significant and meaningful correlations were
      found between PA, NA and HADS scores (ranging from r = .4 to r = .7). Multilevel
      analyses yielded significant change scores for all measures. CONCLUSION: The ESM
      based, transdiagnostic mROM tool can be used reliably in clinical settings: it
      shows adequate psychometric properties, as well as concurrent validity and
      sensitivity to change over time with respect to relevant ROM constructs. Person
      tailored items can be added. In addition, mROM offers added value over standard
      symptom-based ROM, as it provides information on adaptive functioning in the
      daily environment of patients.

PMID- 29023569
TI  - Pancreatic and snake venom presynaptically active phospholipases A2 inhibit
      nicotinic acetylcholine receptors.
AB  - Phospholipases A2 (PLA2s) are enzymes found throughout the animal kingdom. They
      hydrolyze phospholipids in the sn-2 position producing lysophospholipids and
      unsaturated fatty acids, agents that can damage membranes. PLA2s from snake
      venoms have numerous toxic effects, not all of which can be explained by
      phospholipid hydrolysis, and each enzyme has a specific effect. We have earlier
      demonstrated the capability of several snake venom PLA2s with different
      enzymatic, cytotoxic, anticoagulant and antiproliferative properties, to decrease
      acetylcholine-induced currents in Lymnaea stagnalis neurons, and to compete with
      alpha-bungarotoxin for binding to nicotinic acetylcholine receptors (nAChRs) and
      acetylcholine binding protein. Since nAChRs are implicated in postsynaptic and
      presynaptic activities, in this work we probe those PLA2s known to have strong
      presynaptic effects, namely beta-bungarotoxin from Bungarus multicinctus and
      crotoxin from Crotalus durissus terrificus. We also wished to explore whether
      mammalian PLA2s interact with nAChRs, and have examined non-toxic PLA2 from
      porcine pancreas. It was found that porcine pancreatic PLA2 and presynaptic beta
      bungarotoxin blocked currents mediated by nAChRs in Lymnaea neurons with IC50s of
      2.5 and 4.8 MUM, respectively. Crotoxin competed with radioactive alpha
      bungarotoxin for binding to Torpedo and human alpha7 nAChRs and to the
      acetylcholine binding protein. Pancreatic PLA2 interacted similarly with these
      targets; moreover, it inhibited radioactive alpha-bungarotoxin binding to the
      water-soluble extracellular domain of human alpha9 nAChR, and blocked
      acetylcholine induced currents in human alpha9alpha10 nAChRs heterologously
      expressed in Xenopus oocytes. These and our earlier results show that all snake
      PLA2s, including presynaptically active crotoxin and beta-bungarotoxin, as well
      as mammalian pancreatic PLA2, interact with nAChRs. The data obtained suggest
      that this interaction may be a general property of all PLA2s, which should be
      proved by further experiments.

PMID- 29023570
TI  - Species-specific roles of sulfolipid metabolism in acclimation of photosynthetic
      microbes to sulfur-starvation stress.
AB  - Photosynthetic organisms utilize sulfate for the synthesis of sulfur-compounds
      including proteins and a sulfolipid, sulfoquinovosyl diacylglycerol. Upon ambient
      deficiency in sulfate, cells of a green alga, Chlamydomonas reinhardtii, degrade
      the chloroplast membrane sulfolipid to ensure an intracellular-sulfur source for
      necessary protein synthesis. Here, the effects of sulfate-starvation on the
      sulfolipid stability were investigated in another green alga, Chlorella kessleri,
      and two cyanobacteria, Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC
      7942. The results showed that sulfolipid degradation was induced only in C.
      kessleri, raising the possibility that this degradation ability was obtained not
      by cyanobacteria, but by eukaryotic algae during the evolution of photosynthetic
      organisms. Meanwhile, Synechococcus disruptants concerning sqdB and sqdX genes,
      which are involved in successive reactions in the sulfolipid synthesis pathway,
      were respectively characterized in cellular response to sulfate-starvation.
      Phycobilisome degradation intrinsic to Synechococcus, but not to Synechocystis,
      and cell growth under sulfate-starved conditions were repressed in the sqdB and
      sqdX disruptants, respectively, relative to in the wild type. Their distinct
      phenotypes, despite the common loss of the sulfolipid, inferred specific roles of
      sqdB and sqdX. This study demonstrated that sulfolipid metabolism might have been
      developed to enable species- or cyanobacterial-strain dependent processes for
      acclimation to sulfate-starvation.

PMID- 29023571
TI  - PICKLE 2.0: A human protein-protein interaction meta-database employing data
      integration via genetic information ontology.
AB  - It has been acknowledged that source databases recording experimentally supported
      human protein-protein interactions (PPIs) exhibit limited overlap. Thus, the
      reconstruction of a comprehensive PPI network requires appropriate integration of
      multiple heterogeneous primary datasets, presenting the PPIs at various genetic
      reference levels. Existing PPI meta-databases perform integration via
      normalization; namely, PPIs are merged after converted to a certain target level.
      Hence, the node set of the integrated network depends each time on the number and
      type of the combined datasets. Moreover, the irreversible a priori normalization
      process hinders the identification of normalization artifacts in the integrated
      network, which originate from the nonlinearity characterizing the genetic
      information flow. PICKLE (Protein InteraCtion KnowLedgebasE) 2.0 implements a new
      architecture for this recently introduced human PPI meta-database. Its main novel
      feature over the existing meta-databases is its approach to primary PPI dataset
      integration via genetic information ontology. Building upon the PICKLE principles
      of using the reviewed human complete proteome (RHCP) of UniProtKB/Swiss-Prot as
      the reference protein interactor set, and filtering out protein interactions with
      low probability of being direct based on the available evidence, PICKLE 2.0 first
      assembles the RHCP genetic information ontology network by connecting the
      corresponding genes, nucleotide sequences (mRNAs) and proteins (UniProt entries)
      and then integrates PPI datasets by superimposing them on the ontology network
      without any a priori transformations. Importantly, this process allows the
      resulting heterogeneous integrated network to be reversibly normalized to any
      level of genetic reference without loss of the original information, the latter
      being used for identification of normalization biases, and enables the appraisal
      of potential false positive interactions through PPI source database cross
      checking. The PICKLE web-based interface (www.pickle.gr) allows for the
      simultaneous query of multiple entities and provides integrated human PPI
      networks at either the protein (UniProt) or the gene level, at three PPI
      filtering modes.

PMID- 29023572
TI  - Computer aided detection in prostate cancer diagnostics: A promising alternative
      to biopsy? A retrospective study from 104 lesions with histological ground truth.
AB  - BACKGROUND: Prostate cancer (PCa) diagnosis by means of multiparametric magnetic
      resonance imaging (mpMRI) is a current challenge for the development of computer
      aided detection (CAD) tools. An innovative CAD-software (Watson ElementaryTM) was
      proposed to achieve high sensitivity and specificity, as well as to allege a
      correlate to Gleason grade. AIM/OBJECTIVE: To assess the performance of Watson
      ElementaryTM in automated PCa diagnosis in our hospital's database of MRI-guided
      prostate biopsies. METHODS: The evaluation was retrospective for 104 lesions (47
      PCa, 57 benign) from 79, 64.61+/-6.64 year old patients using 3T T2-weighted
      imaging, Apparent Diffusion Coefficient (ADC) maps and dynamic contrast
      enhancement series. Watson ElementaryTM utilizes signal intensity, diffusion
      properties and kinetic profile to compute a proportional Gleason grade predictor,
      termed Malignancy Attention Index (MAI). The analysis focused on (i) the CAD
      sensitivity and specificity to classify suspect lesions and (ii) the MAI
      correlation with the histopathological ground truth. RESULTS: The software
      revealed a sensitivity of 46.80% for PCa classification. The specificity for PCa
      was found to be 75.43% with a positive predictive value of 61.11%, a negative
      predictive value of 63.23% and a false discovery rate of 38.89%. CAD classified
      PCa and benign lesions with equal probability (P 0.06, chi2 test). Accordingly,
      receiver operating characteristic analysis suggests a poor predictive value for
      MAI with an area under curve of 0.65 (P 0.02), which is not superior to the
      performance of board certified observers. Moreover, MAI revealed no significant
      correlation with Gleason grade (P 0.60, Pearson's correlation). CONCLUSION: The
      tested CAD software for mpMRI analysis was a weak PCa biomarker in this dataset.
      Targeted prostate biopsy and histology remains the gold standard for prostate
      cancer diagnosis.

PMID- 29023573
TI  - Enhanced passive screening and diagnosis for gambiense human African
      trypanosomiasis in north-western Uganda - Moving towards elimination.
AB  - INTRODUCTION: The incidence of gambiense human African trypanosomiasis (gHAT) in
      Uganda has been declining, from 198 cases in 2008, to only 20 in 2012.
      Interruption of transmission of the disease by early diagnosis and treatment is
      core to the control and eventual elimination of gHAT. Until recently, the format
      of available screening tests had restricted screening and diagnosis to central
      health facilities (passive screening). We describe a novel strategy that is
      contributing to elimination of gHAT in Uganda through expansion of passive
      screening to the entire population at risk. METHODOLOGY / PRINCIPAL FINDINGS: In
      this strategy, patients who are clinically suspected of having gHAT at primary
      health facilities are screened using a rapid diagnostic test (RDT), followed by
      parasitological confirmation at strategically located microscopy centres. For
      patients who are positive with the RDT and negative by microscopy, blood samples
      undergo further testing using loop-mediated isothermal amplification (LAMP), a
      molecular test that detects parasite DNA. LAMP positive patients are considered
      strong suspects, and are re-evaluated by microscopy. Location and upgrading of
      facilities to perform microscopy and LAMP was informed by results of
      georeferencing and characterization of all public healthcare facilities in the 7
      gHAT endemic districts in Uganda. Three facilities were upgraded to perform RDTs,
      microscopy and LAMP, 9 to perform RDTs and microscopy, and 200 to screen patients
      with RDTs. This reduced the distance that a sick person must travel to be
      screened for gHAT to a median distance of 2.5km compared to 23km previously. In
      this strategy, 9 gHAT cases were diagnosed in 2014, and 4 in 2015. CONCLUSIONS:
      This enhanced passive screening strategy for gHAT has enabled full coverage of
      the population at risk, and is being replicated in other gHAT endemic countries.
      The improvement in case detection is making elimination of the disease in Uganda
      an imminent possibility.

PMID- 29023575
TI  - Different transferability of incompatibility (Inc) P-7 plasmid pCAR1 and IncP-1
      plasmid pBP136 in stirring liquid conditions.
AB  - Self-transmissible plasmids are classified into two types based on their sex
      pili: short and rigid pili, and long and flexible pili. The transferability of
      two plasmids with different types of sex pili, pBP136 and pCAR1, was compared in
      stirring liquid conditions with different cell density. The most probable number
      method to count transconjugants could detect differences in the transfer
      frequency with higher resolution in comparison with the conventional CFU counting
      method. Both plasmids showed higher transfer frequency in high stirring rates
      than static liquid conditions when the donor and recipient density was 106-107
      CFU mL-1. The probability of donor-initiated plasmid transfer was investigated by
      a single-cell-level analysis using a cell sorter. The probability was >36-fold
      higher for pBP136 than for pCAR1; thus, the simulated transfer frequency of
      pBP136 was much higher than that of pCAR1 in stirring liquid conditions.
      Nevertheless, the transfer frequency of pCAR1 was as high as that of pBP136 when
      the donor and recipient cell density was 106 CFU mL-1. This fact indicates that
      the lower probability of the donor pCAR1 to initiate transfer could be overcome
      by its high tolerance to the shearing force between donor and recipient cells
      under higher stirring liquid conditions. Our findings can explain the different
      survival strategies of these two types of plasmids based on their preferences of
      transfer conditions.

PMID- 29023574
TI  - Human cellular and humoral immune responses to Phlebotomus papatasi salivary
      gland antigens in endemic areas differing in prevalence of Leishmania major
      infection.
AB  - BACKGROUND: Sand fly saliva compounds are able to elicit specific immune
      responses that have a significant role in Leishmania parasite establishment and
      disease outcome. Characterizing anti-saliva immune responses in individuals
      living in well defined leishmaniasis endemic areas would provide valuable
      insights regarding their effect on parasite transmission and establishment in
      humans. METHODOLOGY/PRINCIPAL FINDINGS: We explored the cellular and humoral
      immune responses to Phlebotomus (P.) papatasi salivary gland extracts (SGE) in
      individuals living in cutaneous leishmaniasis (CL) old or emerging foci (OF, EF).
      OF was characterized by a higher infection prevalence as assessed by higher
      proportions of leishmanin skin test (LST) positive individuals compared to EF.
      Subjects were further subdivided into healed, asymptomatic or naive groups. We
      showed anti-SGE proliferation in less than 30% of the individuals, regardless of
      the immune status, in both foci. IFN-gamma production was higher in OF and only
      observed in immune individuals from OF and naive subjects from EF. Although IL-10
      was not detected, addition of anti-human IL-10 antibodies revealed an increase in
      proliferation and IFN-gamma production only in individuals from OF. The
      percentage of seropositive individuals was similar in immune and naives groups
      but was significantly higher in OF. No correlation was observed between anti
      saliva immune responses and LST response. High anti-SGE-IgG responses were
      associated with an increased risk of developing ZCL. No differences were observed
      for anti-SGE humoral or cellular responses among naive individuals who converted
      or not their LST response or developed or not ZCL after the transmission season.
      CONCLUSIONS/SIGNIFICANCE: These data suggest that individuals living in an old
      focus characterized by a frequent exposure to sand fly bites and a high
      prevalence of infection, develop higher anti-saliva IgG responses and IFN-gamma
      levels and a skew towards a Th2-type cellular response, probably in favor of
      parasite establishment, compared to those living in an emerging focus.

PMID- 29023577
TI  - Sevoflurane protects rat brain endothelial barrier structure and function after
      hypoxia-reoxygenation injury.
AB  - BACKGROUND: After cerebral injury blood-brain barrier disruption significantly
      impairs brain homeostasis. Volatile anesthetics have been shown to be protective
      in ischemia-reperfusion injury scenarios. Their impact on brain endothelial cells
      after hypoxia-reoxygenation (H/R) has not yet been studied in detail. METHODS:
      Rat brain endothelial cells (RBE4) were exposed to severe hypoxia and
      reoxygenated in air in the presence or absence of sevoflurane. Changes in dextran
      permeability and architecture of the cellular junctional proteins ZO-1 and beta
      catenin were measured. To determine necrosis and apoptosis rate DNA content, LDH
      release and caspase activity were quantified. The role of vascular endothelial
      growth factor (VEGF) as an inflammatory mediator increasing vascular permeability
      was assessed. At the same time, it was evaluated if sevoflurane effects are
      mediated through VEGF. Results were analyzed by unpaired t-tests or one way
      analysis of variance followed by Bonferroni's correction. RESULTS: H/R led to a
      172% increase in permeability (p<0.001), cell swelling and qualitatively but not
      quantitatively modified expression of ZO-1, beta-catenin and F-actin. In the
      presence of sevoflurane during reoxygenation, barrier function improved by 96% (p
      = 0.042) in parallel to a decrease of the cell size and less re-arranged junction
      proteins and F-actin. Sevoflurane-induced improvement of the barrier function
      could not be explained on the level of necrosis or apoptosis as they remained
      unchanged independent of the presence or absence of the volatile anesthetic.
      Increased expression of VEGF after H/R was attenuated by sevoflurane by 34% (p =
      0.004). Barrier protection provided by sevoflurane was similar to the application
      of a blocking VEGF-antibody. Furthermore, the protective effect of sevoflurane
      was abolished in the presence of recombinant VEGF. CONCLUSIONS: In H/R-induced
      rat brain endothelial cell injury sevoflurane maintains endothelial barrier
      function through downregulation of VEGF, which is a key player not only in
      mediating injury, but also with regard to the protective effect of sevoflurane.

PMID- 29023576
TI  - Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial
      cells accelerates coronary artery disease in a mouse model of familial
      hypercholesterolemia.
AB  - OBJECTIVE: Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in
      endothelium leads to arterial calcification in mice. The purpose of this study
      was to examine the effect of elevated endothelial TNAP on coronary
      atherosclerosis. In addition, we aimed to examine endogenous TNAP activity in
      human myocardium. APPROACH AND RESULTS: A vascular pattern of TNAP activity was
      observed in human non-failing, ischemic, and idiopathic dilated hearts (5 per
      group); no differences were noted between groups in this study. Endothelial
      overexpression of TNAP was achieved in mice harboring a homozygous recessive
      mutation in the low density lipoprotein receptor (whc allele) utilizing a Tie2
      cre recombinase (WHC-eTNAP mice). WHC-eTNAP developed significant coronary artery
      calcification at baseline compared WHC controls (4312 vs 0MUm2 alizarin red area,
      p<0.001). Eight weeks after induction of atherosclerosis, lipid deposition in the
      coronary arteries of WHC-eTNAP was increased compared to WHC controls (121633 vs
      9330MUm2 oil red O area, p<0.05). Coronary lesions in WHC-eTNAP mice exhibited
      intimal thickening, calcifications, foam cells, and necrotic cores. This was
      accompanied by the reduction in body weight and left ventricular ejection
      fraction (19.5 vs. 23.6g, p<0.01; 35% vs. 47%, p<0.05). In a placebo-controlled
      experiment under atherogenic conditions, pharmacological inhibition of TNAP in
      WHC-eTNAP mice by a specific inhibitor SBI-425 (30mg*kg-1*d-1, for 5 weeks)
      reduced coronary calcium (78838 vs.144622MUm2) and lipids (30754 vs. 77317MUm2);
      improved body weight (22.4 vs.18.8g) and ejection fraction (59 vs. 47%). The
      effects of SBI-425 were significant in the direct comparisons with placebo but
      disappeared after TNAP-negative placebo-treated group was included in the models
      as healthy controls. CONCLUSIONS: Endogenous TNAP activity is present in human
      cardiac tissues. TNAP overexpression in vascular endothelium in mice leads to an
      unusual course of coronary atherosclerosis, in which calcification precedes lipid
      deposition. The prevalence and significance of this mechanism in human
      atherosclerosis requires further investigations.

PMID- 29023578
TI  - Factors related to environmental barriers experienced by persons with and without
      disabilities in diverse African settings.
AB  - This paper explores differences in experienced environmental barriers between
      individuals with and without disabilities and the impact of additional factors on
      experienced environmental barriers. Data was collected in 2011-2012 by means of a
      two-stage cluster sampling and comprised 400-500 households in different sites in
      South Africa, Sudan Malawi and Namibia. Data were collected through self-report
      survey questionnaires. In addition to descriptive statistics and simple
      statistical tests a structural equation model was developed and tested. The
      combined file comprised 9,307 participants. The Craig Hospital Inventory of
      Environmental Factors was used to assess the level of environmental barriers.
      Transportation, the natural environment and access to health care services
      created the biggest barriers. An exploratory factor analysis yielded support for
      a one component solution for environmental barriers. A scale was constructed by
      adding the items together and dividing by number of items, yielding a range from
      one to five with five representing the highest level of environmental barriers
      and one the lowest. An overall mean value of 1.51 was found. Persons with
      disabilities scored 1.66 and persons without disabilities 1.36 (F = 466.89, p <
      .001). Bivariate regression analyses revealed environmental barriers to be higher
      among rural respondents, increasing with age and severity of disability, and
      lower for those with a higher level of education and with better physical and
      mental health. Gender had an impact only among persons without disabilities,
      where women report more barriers than men. Structural equation model analysis
      showed that socioeconomic status was significantly and negatively associated with
      environmental barriers. Activity limitation is significantly associated with
      environmental barriers when controlling for a number of other individual
      characteristics. Reducing barriers for the general population would go some way
      to reduce the impact of these for persons with activity limitations, but
      additional and specific adaptations will be required to ensure an inclusive
      society.

PMID- 29023580
TI  - Effects of fish movement assumptions on the design of a marine protected area to
      protect an overfished stock.
AB  - Marine Protected Areas (MPA) are important management tools shown to protect
      marine organisms, restore biomass, and increase fisheries yields. While MPAs have
      been successful in meeting these goals for many relatively sedentary species,
      highly mobile organisms may get few benefits from this type of spatial protection
      due to their frequent movement outside the protected area. The use of a large MPA
      can compensate for extensive movement, but testing this empirically is
      challenging, as it requires both large areas and sufficient time series to draw
      conclusions. To overcome this limitation, MPA models have been used to identify
      designs and predict potential outcomes, but these simulations are highly
      sensitive to the assumptions describing the organism's movements. Due to recent
      improvements in computational simulations, it is now possible to include very
      complex movement assumptions in MPA models (e.g. Individual Based Model). These
      have renewed interest in MPA simulations, which implicitly assume that increasing
      the detail in fish movement overcomes the sensitivity to the movement
      assumptions. Nevertheless, a systematic comparison of the designs and outcomes
      obtained under different movement assumptions has not been done. In this paper,
      we use an individual based model, interconnected to population and fishing fleet
      models, to explore the value of increasing the detail of the movement assumptions
      using four scenarios of increasing behavioral complexity: a) random, diffusive
      movement, b) aggregations, c) aggregations that respond to environmental forcing
      (e.g. sea surface temperature), and d) aggregations that respond to environmental
      forcing and are transported by currents. We then compare these models to
      determine how the assumptions affect MPA design, and therefore the effective
      protection of the stocks. Our results show that the optimal MPA size to maximize
      fisheries benefits increases as movement complexity increases from ~10% for the
      diffusive assumption to ~30% when full environment forcing was used. We also
      found that in cases of limited understanding of the movement dynamics of a
      species, simplified assumptions can be used to provide a guide for the minimum
      MPA size needed to effectively protect the stock. However, using oversimplified
      assumptions can produce suboptimal designs and lead to a density underestimation
      of ca. 30%; therefore, the main value of detailed movement dynamics is to provide
      more reliable MPA design and predicted outcomes. Large MPAs can be effective in
      recovering overfished stocks, protect pelagic fish and provide significant
      increases in fisheries yields. Our models provide a means to empirically test
      this spatial management tool, which theoretical evidence consistently suggests as
      an effective alternative to managing highly mobile pelagic stocks.

PMID- 29023579
TI  - Role of the N-terminus for the stability of an amyloid-beta fibril with three
      fold symmetry.
AB  - A key player in Alzheimer's disease is the peptide amyloid-beta (Abeta), whose
      aggregation into small soluble oligomers, protofilaments, and fibrils finally
      leads to plaque deposits in human brains. The aggregation behavior of Abeta is
      strongly modulated by the nature and composition of the peptide's environment and
      by its primary sequence properties. The N-terminal residues of Abeta play an
      important role, because they are known to change the peptide's aggregation
      propensity. Since these residues are for the first time completely resolved at
      the molecular level in a three-fold symmetric fibril structure derived from a
      patient, we chose that system as template for a systematic investigation of the
      influence of the N-terminus upon structural stability. Using atomistic molecular
      dynamics simulations, we examined several fibrillar systems comprising three,
      six, twelve and an infinite number of layers, both with and without the first
      eight residues. First, we found that three layers are not sufficient to stabilize
      the respective Abeta topology. Second, we observed a clear stabilizing effect of
      the N-terminal residues upon the overall fibril fold: truncated Abeta systems
      were less stable than their full-length counterparts. The N-terminal residues
      Arg5, Asp7, and Ser8 were found to form important interfilament contacts
      stabilizing the overall fibril structure of three-fold symmetry. Finally, similar
      structural rearrangements of the truncated Abeta species in different simulations
      prompted us to suggest a potential mechanism involved in the formation of amyloid
      fibrils with three-fold symmetry.

PMID- 29023583
TI  - Correction: Prognostic value of long non-coding RNA CCAT1 expression in patients
      with cancer: A meta-analysis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0179346.].

PMID- 29023581
TI  - Activating and inhibitory receptors on natural killer cells in patients with
      systemic lupus erythematosis-regulation with interleukin-15.
AB  - Natural killer (NK) cells may play an important role in the pathogenesis of SLE.
      Interleukin(IL)-15, an NK-enhancing cytokine, is over-expressed in SLE patients.
      In the present study, we examined the effect of IL-15 on NK cytotoxicity of SLE
      patients, and the expression of various activating and inhibitory NK receptors on
      NK cells from SLE patients in relation to disease activity. We also sought to
      determine how IL-15 would affect the NK receptor expression on NK cells from SLE
      patients. PBMCs were collected from 88 SLE patients with inactive disease
      activity (SLEDAI score<6) and active disease activity (SLEDAI score>=6), 26 age
      matched healthy adults were used as controls. PBMC were incubated in the presence
      or absence of IL-15 (10ng/ml) for eighteen hours. CD3-CD56+ lymphoctes were gated
      using flow cytometry and further divided into CD56dim and CD56bright subsets
      according to the MFI of CD56. We observed that 1. Serum IL-15 was elevated in SLE
      patients, and higher in active disease than in inactive disease; 2. NK
      cytotoxicity of SLE patients was deficient compared to controls and showed an
      impaired response to IL-15 compared to controls; 3.CD69, CD94, NKG2A, NKp30, and
      CD158b on NK cells from SLE patients were higher than controls, and could be
      further enhanced by IL-15; 4. NKp46 expression from SLE patients was higher than
      controls, but down-regulated by IL-15; 5.Deficient NKG2D and NKAT-2 expression
      were found on NK cells from SLE patients, which were enhanced by IL-15; 6. A
      unique NKp46- subset and CD158b+ subsets were observed in NK cells from SLE
      patients but not controls. 7. Unlike controls, CD158k on NK cells from SLE
      patients failed to respond to IL-15. Taken together, we demonstrated the aberrant
      NCR and iNKR expression on NK cells and their distinct response to IL-15 in SLE
      patients. As IL-15 predominantly aggravates the aberrant NKR expression found in
      SLE, IL-15 antagonist may have therapeutic benefits in SLE patients.

PMID- 29023582
TI  - Presence of children in the home and intimate partner violence among women
      seeking elective pregnancy termination.
AB  - INTRODUCTION: Growing evidence identifies adverse health effects for children who
      witness intimate partner violence at home. Research has also identified that
      women seeking elective pregnancy termination are at high risk for partner
      violence. However, little is known about the risk for violence exposure among the
      children of women seeking elective pregnancy termination. METHODS: We conducted a
      cross-sectional study of 957 women seeking elective pregnancy termination at a
      large family planning clinic. All subjects completed a 10-minute, anonymous
      questionnaire administered by computer in a private room. Our main outcome was 12
      month prevalence of physical and/or sexual violence by a current or former
      partner using the Abuse Assessment Screen instrument. The presence of children
      under the age of 18 living with the respondent was the main exposure variable.
      RESULTS: Women with children in the home had more than twice the odds of
      reporting physical and/or sexual IPV in the past year than women with no
      children, controlling for age (AOR: 2.23; 95% CI: 1.41-3.85). The increased odds
      of IPV among women with children as compared to women with no children was
      present across nearly all sociodemographic and lifestyle characteristics, and
      significantly higher for the youngest women (18-20 years). The highest odds for
      abuse occurred among women with children living at home, in a current
      relationship but not living with their current partner, and abused by a former
      partner (AOR = 10.9; 95% CI: 3.07-38.4). CONCLUSION: Nearly one of every 14
      children identified in this study lived in a home with IPV. These findings
      support the development of IPV interventions that are family-centered, as well as
      the integration of trauma-informed care into healthcare settings. Healthcare
      visits for contraception and pregnancy termination may be ideal opportunities for
      implementation of screening and family violence interventions.

PMID- 29023584
TI  - Intravenous fluid prescribing errors in children: Mixed methods analysis of
      critical incidents.
AB  - INTRODUCTION: Recent National Institute for Health and Care Excellence (NICE)
      guidelines aim to improve intravenous (IV) fluid prescribing for children, but
      existing evidence about how and why fluid prescribing errors occur is limited.
      Studying this can lead to more effective implementation, through education and
      systems design. AIMS: Identify types of IV fluid prescribing errors reported in
      practiceAnalyse factors that contribute to errorsProvide guidance to educators
      and those responsible for designing systems. METHODS: Mixed methods observational
      study which analysed critical incident reports relating to IV fluid prescribing
      errors in children aged 0-16, occurring between 2011 and 2015 in UK secondary
      care. We quantified characteristics and types of errors, then qualitatively
      analysed narrative descriptions, identifying underlying contributing factors.
      RESULTS: In the 40 incidents analysed, principal types of errors were incorrect
      rate of fluids, inappropriate choice of solution, and incorrect completion of
      prescription charts. Prescribers had to negotiate complex patients, interactions
      with other practitioners and teams, and challenging work environments; errors
      resulted from these inter-related contributing factors. CONCLUSIONS: This study
      highlights the diverse range and complex nature of IV fluid prescribing errors
      reported in practice. While these findings have the inherent limitations of
      critical incident reports, they point to areas of potential improvement in
      education and systems design. Practising prescribing in context, inducting
      doctors within the many specialties who contribute to care of children, and
      educating them in joint working with nurses and pharmacists could help reduce
      errors.

PMID- 29023585
TI  - Correlations between local peripapillary choroidal thickness and axial length,
      optic disc tilt, and papillo-macular position in young healthy eyes.
AB  - Optical coherence tomography (OCT) has made it possible for clinicians to measure
      the peripapillary choroidal thickness (ppCT) noninvasively in various ocular
      diseases. However, the ocular factors associated with the ppCT have not been
      conclusively determined. The purpose of this study was to determine the
      relationship between the local ppCT and the axial length, optic disc tilt, and
      the angle of the papillo-macular position (PMP) in healthy eyes. This was a
      prospective, observational cross-sectional study of 119 right eyes of 119 healthy
      Japanese volunteers. The ppCT was manually measured at eight sectors around the
      optic disc using the B-scan images of the Topcon 3D OCT RNFL 3.4 mm circle scan.
      The trajectory of the retinal pigment epithelium in the B-scan image was fitted
      to a sine curve using ImageJ, and the amplitude of the sine curve was used to
      determine the degree of the optic disc tilt. The PMP angle was determined in the
      color fundus photographs. The relationships between the ppCT and the axial
      length, the optic disc tilt, and PMP angle were determined by Spearman and
      multiple correlation analyses. The mean age was 25.8 +/- 3.9 years and the mean
      axial length was 25.5 +/- 1.4 mm. The ppCT was significantly and negatively
      associated with the axial length (R = -0.43 to -0.24, P<0.01) and positively
      associated with the PMP angle (R = 0.28 to 0.37, P<0.01) in all eight
      circumpapillary sectors. The temporal and infratemporal ppCTs were significantly
      and negatively associated with the optic disc tilt (R = -0.31, -0.20, P<0.05).
      The results of multiple regression analyses were similar to that of Spearman
      correlation analysis. In conclusion, the axial length and PMP angle can affect
      the ppCT in all circumferential sectors, however the tilt of the optic disc is
      correlated with only some of the sectors. This should be remembered in
      interpreting the ppCT.

PMID- 29023586
TI  - Reduced resting state connectivity and gray matter volume correlate with
      cognitive impairment in minimal hepatic encephalopathy.
AB  - BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is associated with
      cognitive alterations and changes in connectivity. We assessed the relationship
      of the abnormalities of resting-state functional connectivity (rs-FC) and gray
      matter (GM) volume with different cognitive alterations and biochemical
      parameters associated to MHE. METHODS: Thirty-nine cirrhotic patients (26 without
      and 13 with MHE) and 24 controls were widely cognitive assessed with a battery of
      psychometric tests. Atrophy was determined using Voxel-Based Morphometry and rs
      FC was assessed by independent component analysis. Receiver operating
      characteristic (ROC) curves was performed to assess the diagnostic utility of rs
      FC and GM reduction for the discrimination of patients with and without MHE.
      Blood ammonia, cGMP, and levels of pro-inflammatory interleukins were measured.
      RESULTS: MHE patients showed significant decrease of GM volume and lesser degree
      of rs-FC in different networks related to attention and executive functions as
      compared to controls and patients without MHE. There is a progressive reduction
      in rs-FC in the default mode network with the progression of cognitive
      impairment. MHE patients showed GM reduction in the right frontal lobe, right
      insula and right cerebellum compared to patients without MHE. Alterations in GM
      volume and rs-FC correlated with the scores of different cognitive tests.
      CONCLUSIONS: Decreased cognitive performance is associated by reduced rs-FC and
      GM atrophy in MHE patients. These changes could have predictive value for
      detecting MHE.

PMID- 29023588
TI  - Diet alters performance and transcription patterns in Oedaleus asiaticus
      (Orthoptera: Acrididae) grasshoppers.
AB  - We reared Oedaleus asiaticus grasshoppers under four different single-plant diets
      to examine the relationships among diet, performance, stress, and transcription
      patterns. Grasshoppers fed only Artemisia frigida (Asteraceae) were stressed, as
      indicated by their lower growth, size, development, and survival, in comparison
      to grasshoppers fed on any of three grasses, Cleistogenes squarrosa, Leymus
      chinensis, or Stipa krylovii (all Poaceae). We then used transcriptome analysis
      to examine how gene expression levels in O. asiaticus were altered by feeding on
      these diets. Nymphs fed A. frigida had the largest variation in gene expression
      profiles with a total of 299 genes significantly up- or down-regulated compared
      to those feeding on the three grasses: down-regulated genes included those
      involved in cuticle biosynthesis, DNA replication, biosynthesis and metabolism of
      nutrition. The up-regulated genes included stress-resistant and detoxifying
      enzymes. GO and KEGG enrichment analysis also showed that feeding on A. frigida
      could down-regulate biosynthesis and metabolism related pathways, and up-regulate
      stress-resistant and detoxification terms and pathways. Our results show that
      diet significantly altered gene-expression, and that unfavorable, stressful diets
      induce more transcriptional changes than favorable diets. Altered gene-expression
      represents phenotypic plasticity, and many such changes appear to be evolved,
      adaptive responses. The ease and regularity by which individuals shift phenotypes
      via altered transcription suggests that populations consist not of similar, fixed
      phenotypes, but of a collection of ever-changing, divergent phenotypes.

PMID- 29023587
TI  - Genetic variants and traits related to insulin-like growth factor-I and insulin
      resistance and their interaction with lifestyles on postmenopausal colorectal
      cancer risk.
AB  - Genetic variants and traits in metabolic signaling pathways may interact with
      lifestyle factors such as obesity, physical activity, and exogenous estrogen (E),
      influencing postmenopausal colorectal cancer (CRC) risk, but these interrelated
      pathways are not fully understood. In this case-cohort study, we examined 33
      single-nucleotide polymorphisms (SNPs) in genes related to insulin-like growth
      factor-I (IGF-I)/ insulin resistance (IR) traits and signaling pathways, using
      data from 704 postmenopausal women in Women's Health Initiative Observation
      ancillary studies. Stratifying by the lifestyle modifiers, we assessed the
      effects of IGF-I/IR traits (fasting total and free IGF-I, IGF binding protein-3,
      insulin, glucose, and homeostatic model assessment-insulin resistance) on CRC
      risk as a mediator or influencing factor. Six SNPs in the INS, IGF-I, and IGFBP3
      genes were associated with CRC risk, and those associations differed between non
      obese/active and obese/inactive women and between E nonusers and users. Roughly
      30% of the cancer risk due to the SNP was mediated by IGF-I/IR traits. Likewise,
      carriers of 11 SNPs in the IRS1 and AKT1/2 genes (signaling pathway-related
      genetic variants) had different associations with CRC risk between strata, and
      the proportion of the SNP-cancer association explained by traits varied from 30%
      to 50%. Our findings suggest that IGF-I/IR genetic variants interact with
      obesity, physical activity, and exogenous E, altering postmenopausal CRC risk,
      through IGF-I/IR traits, but also through different pathways. Unraveling gene
      phenotype-lifestyle interactions will provide data on potential genetic targets
      in clinical trials for cancer prevention and intervention strategies to reduce
      CRC risk.

PMID- 29023589
TI  - Light transmission aggregometry using pre-coated microtiter plates and a Victor
      X5 plate reader.
AB  - BACKGROUND: Light transmission aggregometry (LTA) can be performed with
      microtiter plates (96-well LTA). When conducting LTA, an agonist is added to
      platelet-rich plasma and the sample is shaken for minutes after which absorbance
      readings are done. Platelet aggregation is detected as decrease in absorbance.
      However, the classical method is cumbersome and therefore microtiter plates can
      be used for concomitant testing of multiple samples. Furthermore, it would be
      convenient to prepare the plate in advance of platelet aggregation testing. Aim:
      The aim of the present study was to establish a simplified 96-well LTA protocol,
      where plates were pre-coated with agonists and stored at -80 C until use.
      RESULTS: We developed and validated a protocol for 96-well LTA using a Victor X5
      plate reader and pre-coated microtiter plates. The minimum requirement of
      platelet-rich plasma was 45 MUL per sample and the sample platelet count should
      not be below 100 x109/L. Optimal absorbance reading was 595 nm wavelengths.
      Platelet aggregation results were higher at 37 degrees C than at room
      temperature. Platelet adherence to wells after stimulation was observed; it was
      not avoided by pre-coating of the wells with gelatin. A range of up to 7
      concentrations for each agonist (collagen, arachidonic acid, adenosine
      diphosphate, thrombin receptor-activating peptide and protease-activated receptor
      4) was tested concomitantly. A transient rise in platelet aggregation was
      observed after 2 minutes of shaking in some samples with low agonist
      concentration, and platelet aggregation was optimal after 10 minutes of shaking
      for samples with high agonist concentration. Plates could be stored at -80
      degrees C for 15 days without significant change in the platelet aggregation
      results. CONCLUSION: The 96-well LTA is suitable for platelet aggregation testing
      and a range of agonist concentrations can be concomitantly tested.

PMID- 29023591
TI  - A combination of selected mapping and clipping to increase energy efficiency of
      OFDM systems.
AB  - We propose an energy efficient combination design for OFDM systems based on
      selected mapping (SLM) and clipping peak-to-average power ratio (PAPR) reduction
      techniques, and show the related energy efficiency (EE) performance analysis. The
      combination of two different PAPR reduction techniques can provide a significant
      benefit in increasing EE, because it can take advantages of both techniques. For
      the combination, we choose the clipping and SLM techniques, since the former
      technique is quite simple and effective, and the latter technique does not cause
      any signal distortion. We provide the structure and the systematic operating
      method, and show the various analyzes to derive the EE gain based on the combined
      technique. Our analysis show that the combined technique increases the EE by 69%
      compared to no PAPR reduction, and by 19.34% compared to only using SLM
      technique.

PMID- 29023590
TI  - De novo assembly and analysis of the transcriptome of Rumex patientia L. during
      cold stress.
AB  - BACKGROUND: Rumex patientia L. is consumed as a green vegetable in several parts
      of the world, and can withstand extremely low temperatures (-35 degrees C).
      However, little or no available genomic data for this species has been reported
      to date. Here, we used Illumina Hiseq technology for transcriptome assembly in R.
      patientia under normal and cold conditions to evaluate how it responds to cold
      stress. RESULTS: After an in-depth RNA-Seq analysis, 115,589 unigenes were
      produced from the assembled transcripts. Based on similarity search analysis with
      seven databases, we obtained and annotated 60,157 assembled unigenes to at least
      one database. In total, 1,179 unigenes that were identified as differentially
      expressed genes (DEGs), including up-regulated (925) and down-regulated ones
      (254), were successfully assigned GO annotations and classified into three major
      metabolic pathways. Ribosome, carbon metabolism, oxidative phosphorylation and
      biosynthesis of amino acids were the most highly enriched pathways according to
      KEGG analysis. Overall, 66 up-regulated genes were identified as putatively
      involved in the response to cold stress, including members of MYB, AP2/ERF, CBF,
      Znf, bZIP, NAC and COR families. CONCLUSION: To our knowledge, this investigation
      was the first to provide a cold-responsive (COR) transcriptome assembly in R.
      patientia. A large number of potential COR genes were identified, suggesting that
      this species is suitable for cultivation in northern China. In summary, these
      data provide valuable information for future research and genomic studies in R.
      patientia.

PMID- 29023593
TI  - Correction: Ambiguity in the processing of Mandarin Chinese relative clauses: One
      factor cannot explain it all.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0178369.].

PMID- 29023592
TI  - Polymer-based precipitation preserves biological activities of extracellular
      vesicles from an endometrial cell line.
AB  - Extracellular vesicles (EVs) are membrane-bound vesicles released by cells and
      act as media for transfer of proteins, small RNAs and mRNAs to distant sites.
      They can be isolated by different methods. However, the biological activities of
      the purified EVs have seldom been studied. In this study, we compared the use of
      ultracentrifugation (UC), ultra-filtration (UF), polymer-based precipitation
      (PBP), and PBP with size-based purification (PBP+SP) for isolation of EVs from
      human endometrial cells and mouse uterine luminal fluid (ULF). Electron
      microscopy revealed that the diameters of the isolated EVs were similar among the
      tested methods. UF recovered the highest number of EVs followed by PBP, while UC
      and PBP+SP were significantly less efficient (P<0.05). Based on the number of EVs
      to-protein ratios, PBP had the least protein contamination, significantly better
      than the other methods (P<0.05). All the isolated EVs expressed exosome-enriched
      proteins CD63, TSG101 and HSP70. Incubation of the trophoblast JEG-3 cells with
      an equal amount of the fluorescence-labelled EVs isolated by the studied methods
      showed that many of the PBP-EVs treated cells were fluorescence positive but only
      a few cells were labelled in the UC- and UF-EVs treated groups. Moreover, the PBP
      EVs could transfer significantly more miRNA to the recipient cells than the other
      3 methods (P<0.05). The PBP method could isolate EVs from mouse ULF; the diameter
      of the isolated EVs was 62+/-19 nm and expressed CD63, TSG101 and HSP70 proteins.
      In conclusion, PBP could best preserve the activities of the isolated EVs among
      the 4 methods studied and was able to isolate EVs from a small volume of sample.
      The simple setup and low equipment demands makes PBP the most suitable method for
      rapid EV assessment and isolation of EVs in clinical and basic research settings.

PMID- 29023594
TI  - First trimester medication abortion practice in the United States and Canada.
AB  - We conducted a cross-sectional survey of abortion facilities from professional
      networks in the United States (US, n = 703) and Canada (n = 94) to estimate the
      prevalence of medication abortion practices in these settings and to look at
      regional differences. Administrators responded to questions on gestational
      limits, while up to five clinicians per facility reported on 2012 medication
      abortion practice. At the time of fielding, mifepristone was not approved in
      Canada. 383 (54.5%) US and 78 (83.0%) Canadian facilities participated. In the
      US, 95.3% offered first trimester medication abortion compared to 25.6% in
      Canada. While 100% of providers were physicians in Canada, just under half
      (49.4%) were advanced practice clinicians in the US, which was more common in
      Eastern and Western states. All Canadian providers used misoprostol; 85.3% with
      methotrexate. 91.4% of US providers used 200 mg of mifepristone and 800 mcg of
      misoprostol, with 96.7% reporting home misoprostol administration. More than
      three-quarters of providers in both countries required an in-person follow-up
      visit, generally with ultrasound. 87.7% of US providers routinely prescribed
      antibiotics compared to 26.2% in Canada. Nonsteroidal anti-inflammatory drugs
      were the most commonly reported analgesic, with regional variation in opioid
      narcotic prescription. In conclusion, medication abortion practice follows
      evidence-based guidelines in the US and Canada. Efforts to update practice based
      on the latest evidence for reducing in-person visits and increasing provision by
      advanced practice clinicians could strengthen these services and reduce barriers
      to access. Research is needed on optimal antibiotic and analgesic use.

PMID- 29023596
TI  - Correction: The carriage of interleukin-1B-31*C allele plus Staphylococcus aureus
      and Haemophilus influenzae increases the risk of recurrent tonsillitis in a
      Mexican population.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0178115.].

PMID- 29023595
TI  - Actinide bioimaging in tissues: Comparison of emulsion and solid track
      autoradiography techniques with the iQID camera.
AB  - This work presents a comparison of three autoradiography techniques for imaging
      biological samples contaminated with actinides: emulsion-based, plastic-based
      autoradiography and a quantitative digital technique, the iQID camera, based on
      the numerical analysis of light from a scintillator screen. In radiation
      toxicology it has been important to develop means of imaging actinide
      distribution in tissues as these radionuclides may be heterogeneously distributed
      within and between tissues after internal contamination. Actinide distribution
      determines which cells are exposed to alpha radiation and is thus potentially
      critical for assessing absorbed dose. The comparison was carried out by
      generating autoradiographs of the same biological samples contaminated with
      actinides with the three autoradiography techniques. These samples were cell
      preparations or tissue sections collected from animals contaminated with
      different physico-chemical forms of actinides. The autoradiograph characteristics
      and the performances of the techniques were evaluated and discussed mainly in
      terms of acquisition process, activity distribution patterns, spatial resolution
      and feasibility of activity quantification. The obtained autoradiographs
      presented similar actinide distribution at low magnification. Out of the three
      techniques, emulsion autoradiography is the only one to provide a highly-resolved
      image of the actinide distribution inherently superimposed on the biological
      sample. Emulsion autoradiography is hence best interpreted at higher
      magnifications. However, this technique is destructive for the biological sample.
      Both emulsion- and plastic-based autoradiography record alpha tracks and thus
      enabled the differentiation between ionized forms of actinides and oxide
      particles. This feature can help in the evaluation of decorporation therapy
      efficacy. The most recent technique, the iQID camera, presents several additional
      features: real-time imaging, separate imaging of alpha particles and gamma rays,
      and alpha activity quantification. The comparison of these three autoradiography
      techniques showed that they are complementary and the choice of the technique
      depends on the purpose of the imaging experiment.

PMID- 29023597
TI  - Discrete pre-processing step effects in registration-based pipelines, a
      preliminary volumetric study on T1-weighted images.
AB  - Pre-processing MRI scans prior to performing volumetric analyses is common
      practice in MRI studies. As pre-processing steps adjust the voxel intensities,
      the space in which the scan exists, and the amount of data in the scan, it is
      possible that the steps have an effect on the volumetric output. To date, studies
      have compared between and not within pipelines, and so the impact of each step is
      unknown. This study aims to quantify the effects of pre-processing steps on
      volumetric measures in T1-weighted scans within a single pipeline. It was our
      hypothesis that pre-processing steps would significantly impact ROI volume
      estimations. One hundred fifteen participants from the OASIS dataset were used,
      where each participant contributed three scans. All scans were then pre-processed
      using a step-wise pipeline. Bilateral hippocampus, putamen, and middle temporal
      gyrus volume estimations were assessed following each successive step, and all
      data were processed by the same pipeline 5 times. Repeated-measures analyses
      tested for a main effects of pipeline step, scan-rescan (for MRI scanner
      consistency) and repeated pipeline runs (for algorithmic consistency). A main
      effect of pipeline step was detected, and interestingly an interaction between
      pipeline step and ROI exists. No effect for either scan-rescan or repeated
      pipeline run was detected. We then supply a correction for noise in the data
      resulting from pre-processing.

PMID- 29023598
TI  - The Greenland shark Somniosus microcephalus-Hemoglobins and ligand-binding
      properties.
AB  - A large amount of data is currently available on the adaptive mechanisms of polar
      bony fish hemoglobins, but structural information on those of cartilaginous
      species is scarce. This study presents the first characterisation of the
      hemoglobin system of one of the longest-living vertebrate species (392 +/- 120
      years), the Arctic shark Somniosus microcephalus. Three major hemoglobins are
      found in its red blood cells and are made of two copies of the same alpha globin
      combined with two copies of three very similar beta subunits. The three
      hemoglobins show very similar oxygenation and carbonylation properties, which are
      unaffected by urea, a very important compound in marine elasmobranch physiology.
      They display identical electronic absorption and resonance Raman spectra,
      indicating that their heme-pocket structures are identical or highly similar. The
      quaternary transition equilibrium between the relaxed (R) and the tense (T)
      states is more dependent on physiological allosteric effectors than in human
      hemoglobin, as also demonstrated in polar teleost hemoglobins. Similar to other
      cartilaginous fishes, we found no evidence for functional differentiation among
      the three isoforms. The very similar ligand-binding properties suggest that
      regulatory control of O2 transport may be at the cellular level and that it may
      involve changes in the cellular concentrations of allosteric effectors and/or
      variations of other systemic factors. The hemoglobins of this polar shark have
      evolved adaptive decreases in O2 affinity in comparison to temperate sharks.

PMID- 29023599
TI  - TCR-independent functions of Th17 cells mediated by the synergistic actions of
      cytokines of the IL-12 and IL-1 families.
AB  - The development of Th17 cells is accompanied by the acquisition of responsiveness
      to both IL-12 and IL-23, cytokines with established roles in the development
      and/or function of Th1 and Th17 cells, respectively. IL-12 signaling promotes
      antigen-dependent Th1 differentiation but, in combination with IL-18, allows the
      antigen-independent perpetuation of Th1 responses. On the other hand, while IL-23
      is dispensable for initial commitment to the Th17 lineage, it promotes the
      pathogenic function of the Th17 cells. In this study, we have examined the
      overlap between Th1 and Th17 cells in their responsiveness to common pro
      inflammatory cytokines and how this affects the antigen-independent cytokine
      responses of Th17 cells. We found that in addition to the IL-1 receptor,
      developing Th17 cells also up-regulate the IL-18 receptor. Consequently, in the
      presence of IL-1beta or IL-18, and in the absence of TCR activation, Th17 cells
      produce Th17 lineage cytokines in a STAT3-dependent manner when stimulated with
      IL-23, and IFN(c) via a STAT4-dependent mechanism when stimulated with IL-12.
      Thus, building on previous findings of antigen-induced plasticity of Th17 cells,
      our results indicate that this potential of Th17 cells extends to their cytokine
      dependent antigen-independent responses. Collectively, our data suggest a model
      whereby signaling via either IL-1beta or IL-18 allows for bystander responses of
      Th17 cells to pathogens or pathogen products that differentially activate innate
      cell production of IL-12 or IL-23.

PMID- 29023600
TI  - Reduced accumulation of defective viral genomes contributes to severe outcome in
      influenza virus infected patients.
AB  - Influenza A virus (IAV) infection can be severe or even lethal in toddlers, the
      elderly and patients with certain medical conditions. Infection of apparently
      healthy individuals nonetheless accounts for many severe disease cases and
      deaths, suggesting that viruses with increased pathogenicity co-circulate with
      pandemic or epidemic viruses. Looking for potential virulence factors, we have
      identified a polymerase PA D529N mutation detected in a fatal IAV case, whose
      introduction into two different recombinant virus backbones, led to reduced
      defective viral genomes (DVGs) production. This mutation conferred low induction
      of antiviral response in infected cells and increased pathogenesis in mice. To
      analyze the association between low DVGs production and pathogenesis in humans,
      we performed a genomic analysis of viruses isolated from a cohort of previously
      healthy individuals who suffered highly severe IAV infection requiring admission
      to Intensive Care Unit and patients with fatal outcome who additionally showed
      underlying medical conditions. These viruses were compared with those isolated
      from a cohort of mild IAV patients. Viruses with fewer DVGs accumulation were
      observed in patients with highly severe/fatal outcome than in those with mild
      disease, suggesting that low DVGs abundance constitutes a new virulence
      pathogenic marker in humans.

PMID- 29023603
TI  - Correction: Does a presentation's medium affect its message? PowerPoint, Prezi,
      and oral presentations.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0178774.].

PMID- 29023602
TI  - Trace metal release after minimally-invasive repair of pectus excavatum.
AB  - BACKGROUND: Several studies have shown a high incidence of metal allergy after
      minimally-invasive repair of pectus excavatum (MIRPE). We postulated that MIRPE
      is associated with a significant release of trace metal ions, possibly causing
      the allergic symptoms. METHODS: We evaluated the concentration with chromium,
      cobalt and nickel in blood, urine and tissue in patients prior to MIRPE and in
      patients who underwent an explantation of the stainless-steel bar(s) after three
      years. RESULTS: Our study group consisted of 20 patients (mean age 19 years) who
      had bar explantation and our control group included 20 patients (mean age 16
      years) prior to MIRPE. At the time of bar removal we detected significantly
      elevated concentrations of chromium and nickel in the tissue compared to patients
      prior to the procedure (p<0,001). We also found a significant increase in the
      levels of chromium in urine and nickel in blood in patients three years post
      MIRPE (p<0,001). Four patients temporarily developed symptoms of metal allergy,
      all had elevated metal values in blood and urine at explantation. CONCLUSIONS:
      Minimally-invasive repair of pectus excavatum can lead to a significant trace
      metal exposure.

PMID- 29023604
TI  - Correction: Targeted high throughput sequencing in hereditary ataxia and spastic
      paraplegia.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0174667.].

PMID- 29023601
TI  - Adenovirus vector-based multi-epitope vaccine provides partial protection against
      H5, H7, and H9 avian influenza viruses.
AB  - The emergence of H5, H7, and H9 avian influenza virus subtypes in humans reveals
      their pandemic potential. Although human-to-human transmission has been limited,
      the genetic reassortment of the avian and human/porcine influenza viruses or
      mutations in some of the genes resulting in virus replication in the upper
      respiratory tract of humans could generate novel pandemic influenza viruses.
      Current vaccines do not provide cross protection against antigenically distinct
      strains of the H5, H7, and H9 influenza viruses. Therefore, newer vaccine
      approaches are needed to overcome these potential threats. We developed an egg
      independent, adenovirus vector-based, multi-epitope (ME) vaccine approach using
      the relatively conserved immunogenic domains of the H5N1 influenza virus [M2
      ectodomain (M2e), hemagglutinin (HA) fusion domain (HFD), T-cell epitope of
      nucleoprotein (TNP). and HA alpha-helix domain (HalphaD)]. Our ME vaccine induced
      humoral and cell-mediated immune responses and caused a significant reduction in
      the viral loads in the lungs of vaccinated mice that were challenged with
      antigenically distinct H5, H7, or H9 avian influenza viruses. These results
      suggest that our ME vaccine approach provided broad protection against the avian
      influenza viruses. Further improvement of this vaccine will lead to a pre
      pandemic vaccine that may lower morbidity, hinder transmission, and prevent
      mortality in a pandemic situation before a strain-matched vaccine becomes
      available.

PMID- 29023606
TI  - Efficacy of Er:YAG Laser in the Decontamination of Peri-implant Disease: A One
      Year Prospective Closed Cohort Study.
AB  - A significant number of articles have been published to describe a variety of
      techniques for the treatment of peri-implant disease, with varying success.
      Previous reports have presented limited data on the use of lasers for the
      decontamination of implant surfaces prior to defect augmentation using guided
      bone regeneration techniques. The current study is a prospective closed cohort
      study of 20 patients with a follow-up of 1 year. It was established to assess the
      efficacy of the Er:YAG water-cooled laser following initially promising reports
      suggesting the laser can decontaminate and sterilize the implant surface and
      allow for reosseointegration of the affected portion of the implant.

PMID- 29023605
TI  - Involvement of the Arg566 residue of Aeromonas sobria serine protease in
      substrate specificity.
AB  - Aeromonas sobria serine protease (ASP) is an extracellular serine protease
      secreted by the organism. Here, we identified the amino acid residue of ASP that
      contributes to substrate specificity by using both synthetic peptides and
      biological protein components. The results showed that the arginine residue at
      position 566 (Arg-566) of ASP, which is located in the extra occluding region of
      ASP close to an entrance of the catalytic cavity, is involved in the substrate
      specificity. A substitutional point mutation of the Arg-566 residue of ASP to Ala
      residue (ASP[R566A]) caused a decrease of the proteolytic efficiency for a
      certain substrate. In addition, ASP lost the ability to recognize the primary
      substrate by such a point mutation, and ASP[R566A] reacted to a wide range of
      synthetic substrates. It is likely that Arg-566 causes an interaction with the
      amino acid residue at position P3 of the substrate, which is the third amino acid
      residue upstream from the cleavage site. Another study using ORF2 protein, a
      chaperone protein of ASP, further suggested that Arg-566 could also play an
      important role in interaction with ORF2. We therefore conclude that the Arg-566
      residue of ASP is likely responsible for the selection of substrates.

PMID- 29023607
TI  - Immediate Palatal Molar Implants: A Simple, Safe, Minimally Invasive Technique.
AB  - The purpose of this study was to determine whether a single immediate implant
      placed into the postextraction palatal socket of a maxillary molar would be as
      efficacious as a single implant placed centrally in a staged approach. A total of
      61 immediate implants were placed in 52 patients and restored after 6 months.
      Periotest and Osstell were used to determine implant stability, and cone beam
      computed tomography was used for marginal bone level assessment. During the 2
      year follow-up, implant survival was 100%. It was concluded that immediate
      palatal implants can safely restore extracted molars in the maxilla.

PMID- 29023608
TI  - A Retrospective Periodontal Assessment of 137 Teeth After Featheredge Preparation
      and Gingittage.
AB  - The aim of this study was to retrospectively evaluate the periodontal response of
      periodontally healthy teeth prosthetically restored using a featheredge finish
      line preparation combined with a light rotary curettage (gingittage). A total of
      137 restored teeth were included in the study. Mean follow-up time was 18.2
      months (range: 6 to 60 months). Bleeding on probing was noted in 18% of cases,
      while the Plaque Index was found to be 11%. The probing depth in 99.4% of cases
      was <= 3 mm. In only 7 cases (5.1%), a slight restoration margin exposure was
      recorded. Although randomized controlled studies with longer follow-up are
      advocated, the present investigation seems to suggest that this protocol is a
      viable procedure.

PMID- 29023609
TI  - Thickness of the Buccal Plate in Posterior Teeth: A Prospective Cone Beam
      Computed Tomography Study.
AB  - Buccal plate thickness is an important clinical parameter for postextraction
      implant treatment planning. The purpose of this study was to assess buccal plate
      thickness of the posterior maxilla and mandible using cone beam computed
      tomography (CBCT). A total of 265 patients and 934 teeth met the inclusion
      criteria for this study. CBCT volumes were taken and aligned for measurement at
      the ideal midsagittal cross-section. Buccal plate thickness was measured at 1, 3,
      and 5 mm apical to the alveolar crest. The frequency of thick (>= 1 mm), thin (<
      1 mm), and radiographic absence of the buccal plate were determined. The
      frequency of thin buccal plate decreases from anterior to posterior, with first
      premolars and first molar mesial roots most affected. Radiographic absence of the
      buccal plate was more common in the mandible, at first premolars, and among
      women. Thin and absent buccal plate are not uncommon in the posterior jaws;
      consequently, ridge preservation may be indicated even at posterior teeth.

PMID- 29023610
TI  - The Management of Peri-implant Mucosa Deficiencies in Esthetic Sites: Case Report
      of a Combined Surgical-Prosthetic Approach.
AB  - In cases of single missing teeth, implant rehabilitation is generally the
      preferred treatment option. However, obtaining pleasing esthetic results in the
      anterior maxillary region and maintaining or rebuilding peri-implant papillae
      remain challenging tasks. The loss of papillae may cause not just functional but
      also phonetic and esthetic problems. There is scarce information on the
      reliability of surgical approaches concerning the peri-implant papilla. The
      purpose of this case report is to present a modified prosthetic-surgical
      technique to enhance the convex facial contour of the peri-implant mucosa and
      volume and height of papillary tissue in an esthetically highly demanding
      patient.

PMID- 29023611
TI  - Adjunctive Effect of Autologous Platelet-Rich Fibrin in the Treatment of
      Intrabony Defects in Localized Aggressive Periodontitis Patients: A Randomized
      Controlled Split-Mouth Clinical Trial.
AB  - The aim of this study was to investigate the clinical and radiologic efficacy of
      autologous platelet-rich fibrin (PRF) in the treatment of intrabony defects
      associated with localized aggressive periodontitis (LAP). A total of 30 sites, 2
      sites per individual in 15 LAP patients, were treated with modified flap
      operation (MFO; Kirkland flap) alone or combined with autologous PRF. The study
      variables included plaque index, sulcus bleeding index, probing depth (PD),
      clinical attachment level (CAL), and gingival marginal level at baseline and 12
      months postoperatively. The radiographic bone fill (RBF) on standardized
      radiographs was assessed after a year using image analysis software. The
      improvements in PD, CAL, and RBF in test sites compared to control sites were
      statistically significant (P < .05). Mean CAL gain and bone fill in the test
      sites were 4.0 +/- 0.63 mm and 3.09 mm, respectively. Almost 80% of the PRF
      treated sites showed >= 50% bone fill with minimal marginal tissue recession. Use
      of PRF significantly enhances the clinical and radiographic outcomes of open flap
      debridement in the treatment of periodontal intraosseous defects in patients
      affected by LAP.

PMID- 29023612
TI  - A Minimally Invasive Approach Using a 4-mm Implant Without Extraction of Impacted
      Maxillary Canine: Four-Year Postloading Results.
AB  - The aim of this case report was to suggest an alternative minimally invasive
      surgical approach to an impacted maxillary canine using a 4-mm-long implant for a
      fixed prosthetic rehabilitation, avoiding tooth extraction or surgically forced
      extrusion and exploiting the 6 mm of coronal bone availability. At 4 years
      postloading, the implant was healthy and well integrated with stable marginal
      bone levels. The 4-mm length of the implant reduced operative times, postsurgical
      morbidity, possible complications, and costs. Short implants might be an
      alternative to traditional, more invasive surgical procedures used in the
      rehabilitative treatment of impacted maxillary canines.

PMID- 29023614
TI  - Virtual Simulation of Periodontal Surgery Including Presurgical CAD/CAM
      Fabrication of Tooth-Colored Removable Splints on the Basis of CBCT Data: A Case
      Report.
AB  - Innovative digital diagnostic, design, and manufacturing technologies combined
      with high-performance polymers offer new possibilities to facilitate complex
      interdisciplinary treatment procedures. This article reports on the interaction
      of different digital technologies, from presurgical digital simulation of
      periodontal surgery to final prosthodontic rehabilitation, in a case of
      amelogenesis imperfecta in a 17-year-old girl. The aim was to digitally determine
      the treatment outcome by three-dimensional simulation of the soft tissue removal
      and to create computer-aided design/computer-assisted manufacture tooth-colored
      splints before the clinical treatment. The case report shows the synergy of the
      combination of multiple digital technologies for a predictable periodontal and
      prosthetic treatment outcome.

PMID- 29023613
TI  - Comparative Study of rhPDGF-BB Plus Equine-Derived Bone Matrix Versus rhPDGF-BB
      Plus beta-TCP in the Treatment of Periodontal Defects.
AB  - The purpose of this study was to evaluate the efficacy and safety of equine
      derived bone matrix as a carrier for recombinant human platelet-derived growth
      factor BB (rhPDGF-BB) versus beta-tricalcium phosphate (beta-TCP) for the
      treatment of intraosseous periodontal defects in adult patients. This study was
      performed on 32 adults with advanced periodontal disease. Eligible subjects were
      randomized in 1:1 ratio into a test (rhPDGF-BB-coated equine-derived bone matrix)
      or control group (rhPDGF-BB-coated beta-TCP). Probing pocket depth (PD), clinical
      attachment level (CAL), gingival recession (GR), and defect depth on radiographs
      were measured at 2 weeks before surgery, on the day of surgery (DOS), and 6
      months postsurgery (6MPS). The clinical and radiographic data were analyzed over
      the test period. Statistically significant PD reductions and CAL gain between
      baseline and 6MPS and between ODS and 6MPS were seen in both groups (P < .01). No
      statistically significant differences in PD reduction were found between groups.
      However, the test group showed significant CAL gain between DOS and 6MPS. The
      radiographic bone level change was statistically significant compared to baseline
      (P < .01) in both groups. The results suggested that equine-derived bone matrix
      is a viable, effective, and safe carrier scaffold for rhPDGF in periodontal
      defects.

PMID- 29023615
TI  - The Lip-Tooth-Ridge Classification: A Guidepost for Edentulous Maxillary Arches.
      Diagnosis, Risk Assessment, and Implant Treatment Indications.
AB  - Prosthetic rehabilitation of the edentulous maxilla is known to be challenging
      and requires meticulous planning. The purpose of this article is to describe a
      novel classification system, the Lip-Tooth-Ridge (LTR), that offers a guidepost
      for treatment planning the edentulous maxilla for fixed or removable prostheses.
      This tool will help clinicians identify the final prosthetic design and will
      provide a case-specific risk assessment guide regarding two different areas. A
      high (HER) or low (LER) esthetic risk will be determined based on lip dynamics,
      as well as a high or low structural risk according to the prosthetic space
      availability.

PMID- 29023616
TI  - Clinical and Patient-Centered Outcomes Following Treatment of Multiple Gingival
      Recessions Using Acellular Dermal Matrix Allografts.
AB  - The aim of this case series was to evaluate clinical and patient-centered
      outcomes when treating multiple recessions (Miller Class I, II, and III)
      affecting five or more teeth in a single procedure using acellular dermal matrix
      in 18 eligible participants (mean of 7.4 +/- 1.7 recessions/patient). Low mean
      visual analog scale pain scores (0.7 +/- 0.8) and analgesic consumption (2.3 +/-
      2.5 tablets) were reported from days 0 to 6 postoperatively. Mean baseline
      recession depth was 2.1 +/- 1 mm. At 1 year postsurgery, mean percent root
      coverage was 87.1% +/- 18.3%, and complete root coverage was achieved in 61.7% of
      recessions with statistically significant differences between smokers and
      nonsmokers.

PMID- 29023617
TI  - Socket Shield Technique for Implant Placement in the Esthetic Zone: A Case
      Report.
AB  - Improvements in implant design, placement protocols, and sequences for
      reconstruction in the anterior region have enabled clinicians to provide their
      patients with esthetically acceptable results. Yet from a clinical standpoint,
      the predictable preservation of the peri-implant soft tissue remains challenging
      and tissue grafting is often necessary to compensate for ridge contour changes in
      postextraction sites. In animal and clinical studies, the socket shield technique
      has shown its potential to prevent resorption of buccal tissues. This 24-month
      follow-up case report presents a 47-year-old patient with a failing maxillary
      incisor replaced with an immediately placed single implant in conjunction with
      the socket shield technique.

PMID- 29023618
TI  - Reconstruction of Atrophied Posterior Mandible with an Inlay Technique and
      Allograft Block: Technical Description and Histologic Case Reports.
AB  - This paper presents a technical description of the inlay technique performed with
      an allograft block in the reconstruction of a severely atrophic posterior
      mandible. It includes a histologic case series of five patients treated with the
      same grafting procedure and rehabilitated with dental implants 2 months after
      placement of the graft. The histologic analysis showed large amounts of newly
      formed bone in tight connection with the allograft and large marrow spaces with
      intense cellular activity and the presence of osteocytes. Allografts might serve
      as an alternative to autogenous and heterologous grafting in posterior mandible
      augmentation using the inlay technique.

PMID- 29023619
TI  - The Sinus Membrane-Maxillary Lateral Wall Complex: Histologic Description and
      Clinical Implications for Maxillary Sinus Floor Elevation.
AB  - Maxillary sinus floor elevation has been documented as a safe and predictable
      procedure for gaining vertical bone height in the atrophic posterior maxillae.
      Conversely, there is a lack of basic research on the characteristics of the union
      between the sinus membrane (SM) and the bone. Clinical implications of an
      impaired union in healthy or pathologic membranes remain unknown. The objective
      of this study was to present a comprehensive histologic and morphologic
      description of the sinus membrane-lateral bone wall complex. In 14 fresh cadaver
      heads, 28 lateral wall sinus augmentation procedures were performed to obtain SM
      samples. Samples were assessed using hematoxylin-eosin, Masson trichrome, and
      toluidine blue staining and immunofluorescence and immunohistochemistry
      procedures. Specimens were coded and studied by a trained examiner using an
      optical microscope at *4, *10, *40, and *100 objectives. Thickness and
      inflammation status were assessed in these samples. Overall SM thickness of the
      samples was 0.40 +/- 0.12 mm and was positively correlated to the inflammatory
      condition of the membranes. Such low values are the consequence of limited
      inflammation. Most of the fibers and cells in the deeper layers of the SM ran in
      a horizontal direction, oriented parallel to the underlying bone wall. In the
      immunohistochemistry study, 3 out of 7 samples showed a certain degree of nestin
      expression, suggesting osteogenic potential in spite of the elderly specimens.
      Large variations in thickness across the SM were found. These were noted to be
      partially correlated to the SM inflammatory status. The vast majority of the
      fibers were oriented parallel to the maxillary lateral wall, and only a few
      isolated areas showed a stronger perpendicular attachment. This might indicate
      the surpassing importance of the SM inflammatory status, operator skill, and
      other anatomical factors over the sinus membrane-maxillary lateral wall complex
      interface. Moreover, about half of the SM investigated were positive for nestin,
      indicating their osteogenic potential.

PMID- 29023620
TI  - Analysis of Morphologic Attributes in Dental Esthetics: A New Concept.
AB  - An interdisciplinary approach to esthetics requires a comprehensive treatment
      plan formulated through evaluation of several restorative and periodontal
      parameters that influence the esthetic zone. A total of 25 subjects (13 women and
      12 men, with an age range of 18 to 23 years) participated in the study.
      Parameters such as gingival biotype on the labial aspect, crown width to crown
      length ratio, and interdental papilla proportion, with respect to the maxillary
      anterior teeth, were determined. An attempt was made to establish a correlation
      between these components, and a positive correlation was found. A careful
      preoperative diagnosis of these parameters is thus essential, especially in the
      esthetic zone.

PMID- 29023621
TI  - Bond Strength of Self-Adhering Materials: Effect of Dentin-Desensitizing
      Treatment with a CPP-ACP Paste.
AB  - This study investigated the effect of dentin-desensitizing treatment with a
      casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) paste on shear bond
      strength (SBS) of two types of self-adhering (SA) restorative materials: resin
      modified glass-ionomer (Fuji II LC, GC) and self-adhering flowable composite
      resin (Vertise Flow, Kerr). Flat and smear layer-free dentin surfaces from 48
      extracted molars were prepared and divided into four groups (n = 12 per group)
      according to Fuji II LC or Vertise Flow and CPP-ACP pretreatment or not. After
      SBS testing, data were statistically analyzed. The adhesive interfaces were
      examined by scanning electron microscopy. SBS was significantly affected by CPP
      ACP treatment (P < .001) and SA material (P < .05). The interaction of the two
      factors was not significant. The results suggested that the CPP-ACP pretreatment
      of the exposed dentin could have a beneficial effect on bonding ability and
      interfacial integrity of both SA materials so that intimately adapted interfaces
      were observed in CPP-ACP groups.

PMID- 29023622
TI  - Osseous Healing Around Immediate Implants Placed Using Contour Augmentation: A
      Prospective Case Series.
AB  - The purpose of this study was to prospectively evaluate the dimensional bone
      changes around implants placed immediately with buccal contour augmentation.
      Patients with hopeless maxillary anterior teeth were treated with extraction,
      immediate implant placement, and simultaneous buccal contour augmentation. Hard
      tissue measurements were recorded at the time of implant placement and after 3
      months of healing. All implants (N = 18) successfully osseointegrated with a mean
      buccal bone thickness of 2.94 +/- 0.21 mm (mean +/- SE) at the implant platform.
      This was significantly greater compared to previous data on immediate implants
      placed without contour augmentation (2.32 +/- 0.17 mm). Buccal contour
      augmentation in conjunction with immediate implant placement significantly
      increased peri-implant buccal bone thickness after 3 months of healing.

PMID- 29023623
TI  - Vertical Guided Bone Regeneration for a Single Missing Tooth Span with Titanium
      Reinforced d-PTFE Membranes: Clinical Considerations and Observations of 10
      Consecutive Cases with up to 36 Months Follow-up.
AB  - Vertical guided bone regeneration (GBR) using titanium-reinforced
      polytetrafluoroethylene (PTFE) membranes is a well-established technique and is
      considered technique sensitive. When using PTFE membranes, complications usually
      arise in the crestal incision or next to the neighboring tooth of the treated
      span. Most studies available describe either distal free end or multiple missing
      teeth span situations. Treating a single missing tooth span combines the
      challenge of two neighboring teeth and a smaller flap, which is more difficult to
      adapt to the augmented environment. This article describes 10 single span cases
      treated with vertical GBR using high-density PTFE membranes, highlighting
      clinical guidelines for preoperative care, flap design, and suturing.

PMID- 29023624
TI  - Two-Year Clinical Evaluation of Pedicled Buccal Fat Pad Alone and with Emdogain
      for Root Coverage of Severe Gingival Recession Defects: A Case Series.
AB  - Gingival recession is defined as an apical displacement of the gingival margin
      beyond the cementoenamel junction leading to serious consequences, including
      exposure of the root surface, loss of periodontal attachment, root sensitivity to
      hot and cold air, and esthetic problems. The aim of this study was to evaluate
      the long-term effect of pedicled buccal fat pad (PBFP) alone and with Emdogain in
      covering severe gingival recession defects and restoring tooth function. A total
      of 10 severe buccal recession defects in maxillary first molars were selected to
      be treated with PBFP, with Emdogain (group I; n = 5) or alone (group II; n = 5).
      Probing depth, clinical attachment level, depth of the gingival recession, width
      of the keratinized gingiva, and tooth mobility were recorded and statistically
      analyzed at baseline and during follow-up recalls until 2 years postoperatively.
      At 2 years, the percentage of root coverage was 60.18% and 59.07% for group I and
      group II, respectively, with significant differences compared to baseline and all
      follow-up times for each group but with statistically significant differences
      between groups (P > .05). Emdogain with PBFP did not show significant improvement
      compared to PBFP alone in terms of root coverage percentage. PBFP alone may be
      the better treatment for severe gingival recession defects.

PMID- 29023627
TI  - Falls and disability among female cancer survivors.

PMID- 29023625
TI  - Readily Identifiable Risk Factors of Nursing Home Residents' Oral Hygiene:
      Dementia, Hospice, and Length of Stay.
AB  - BACKGROUND/OBJECTIVES: The poor oral hygiene of nursing home (NH) residents is a
      matter of increasing concern, especially because of its relationship with
      pneumonia and other health events. Because details and related risk factors in
      this area are scant and providers need to be able to easily identify those
      residents at most risk, this study comprehensively examined the plaque, gingival,
      and denture status of NH residents, as well as readily available correlates of
      those indicators of oral hygiene, including items from the Minimum Data Set
      (MDS). DESIGN: Oral hygiene assessment and chart abstract conducted on a cross
      section of NH residents. SETTING: NHs in North Carolina (N = 14). PARTICIPANTS:
      NH residents (N = 506). MEASUREMENTS: Descriptive data from the MDS and
      assessments using three standardized measures: the Plaque Index for Long-Term
      Care (PI-LTC), the Gingival Index for Long-Term Care (GI-LTC), and the Denture
      Plaque Index (DPI). RESULTS: Oral hygiene scores averaged 1.7 (of 3) for the PI
      LTC, 1.5 (of 4) for the GI-LTC, and 2.2 (of 4) for the DPI. Factors most strongly
      associated with poor oral hygiene scores included having dementia, being on
      hospice care, and longer stay. MDS ratings of gingivitis differed significantly
      from oral hygiene assessments. CONCLUSIONS: The findings identify resident
      subgroups at especially high risk of poor oral health who can be targeted in
      quality improvement efforts related to oral hygiene; they also indicate need to
      improve the accuracy of how MDS items are completed.

PMID- 29023626
TI  - Bayesian variable selection for multistate Markov models with interval-censored
      data in an ecological momentary assessment study of smoking cessation.
AB  - The application of sophisticated analytical methods to intensive longitudinal
      data, collected with ecological momentary assessments (EMA), has helped
      researchers better understand smoking behaviors after a quit attempt.
      Unfortunately, the wealth of information captured with EMAs is typically
      underutilized in practice. Thus, novel methods are needed to extract this
      information in exploratory research studies. One of the main objectives of
      intensive longitudinal data analysis is identifying relations between risk
      factors and outcomes of interest. Our goal is to develop and apply expectation
      maximization variable selection for Bayesian multistate Markov models with
      interval-censored data to generate new insights into the relation between
      potential risk factors and transitions between smoking states. Through
      simulation, we demonstrate the effectiveness of our method in identifying
      associated risk factors and its ability to outperform the LASSO in a special
      case. Additionally, we use the expectation conditional-maximization algorithm to
      simplify estimation, a deterministic annealing variant to reduce the algorithm's
      dependence on starting values, and Louis's method to estimate unknown parameter
      uncertainty. We then apply our method to intensive longitudinal data collected
      with EMA to identify risk factors associated with transitions between smoking
      states after a quit attempt in a cohort of socioeconomically disadvantaged
      smokers who were interested in quitting.

PMID- 29023629
TI  - Gastric decompression before laparoscopic entry via Palmer's point.

PMID- 29023628
TI  - Ethnic derivation of the Ainu inferred from ancient mitochondrial DNA data.
AB  - OBJECTIVES: The Ainu, the indigenous people living on the northernmost island of
      Japan, Hokkaido, have long been a focus of anthropological interest because of
      their cultural, linguistic, and physical identity. A major problem with genetic
      studies on the Ainu is that the previously published data stemmed almost
      exclusively from only 51 modern-day individuals living in Biratori Town, central
      Hokkaido. To clarify the actual genetic characteristics of the Ainu, individuals
      who are less influenced by mainland Japanese, who started large-scale immigration
      into Hokkaido about 150 years ago, should be examined. Moreover, the samples
      should be collected from all over Hokkaido. MATERIALS AND METHODS: Mitochondrial
      DNA haplogroups of 94 Ainu individuals from the Edo era were successfully
      determined by analyzing haplogroup-defining polymorphisms in the hypervariable
      and coding regions. Thereafter, their frequencies were compared to those of other
      populations. RESULTS: Our findings indicate that the Ainu still retain the
      matrilineage of the Hokkaido Jomon people. However, the Siberian influence on
      this population is far greater than previously recognized. Moreover, the
      influence of mainland Japanese is evident, especially in the southwestern part of
      Hokkaido that is adjacent to Honshu, the main island of Japan. DISCUSSION: Our
      results suggest that the Ainu were formed from the Hokkaido Jomon people, but
      subsequently underwent considerable admixture with adjacent populations. The
      present study strongly recommends revision of the widely accepted dual-structure
      model for the population history of the Japanese, in which the Ainu are assumed
      to be the direct descendants of the Jomon people.

PMID- 29023630
TI  - The HMGB1 is increased in CSF of patients with an Anti-NMDAR encephalitis.
AB  - BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an
      autoimmune disorder of the central nervous system (CNS). Interleukin (IL)-6 and
      IL-17A may play important roles in the pathogenesis of this disease. High
      mobility group box protein 1 (HMGB1), a small but highly conserved ubiquitous
      protein, is recognized to be a potent innate inflammatory mediator that can
      activate the nuclear factor light chain enhancer of activated B cells and release
      cytokines such as IL-6 and IL-17A when released extracellularly. However, whether
      cerebrospinal fluid (CSF) HMGB1 levels are altered in anti-NMDAR encephalitis is
      still unclear. OBJECTIVE: The aim of this study was to determine whether a
      correlation exists between the CSF concentrations of HMGB1 and IL-6 and IL-17A in
      anti-NMDAR encephalitis patients. We also sought to assess whether HMGB1
      influences the clinical outcomes in anti-NMDAR encephalitis patients. METHODS:
      Thirty-three patients with anti-NMDAR antibodies and 38 controls were recruited.
      CSF HMGB1 was measured using an enzyme-linked immunosorbent assay. The main
      clinical outcomes were evaluated using the modified Rankin scale (mRS). The data
      were extracted using microarray analysis software. RESULTS AND CONCLUSION: Our
      results showed significant increases in CSF HMGB1, IL-6, and IL-17A (P < .05) in
      anti-NMDAR encephalitis patients. But between 3 months' mRS scores in anti-NMDAR
      encephalitis patients and CSF data, there was no correlation. Our study suggests
      that HMGB1 CSF levels are increased in patients with anti-NMDAR encephalitis and
      reflect the underlying neuroinflammatory process.

PMID- 29023631
TI  - Population-based study of factors predicting treatment intention in patients with
      locally recurrent rectal cancer.
AB  - BACKGROUND: Local recurrence of rectal cancer (LRRC) is associated with poor
      survival unless curative treatment is performed. The aim of this study was to
      investigate predictive factors for treatment with curative intent in patients
      with LRRC. METHODS: Population-based data for patients treated for primary rectal
      cancer between 1995 and 2002, and with LRRC reported as first event were
      collected from the Swedish Colorectal Cancer Registry and medical records. The
      associations between patient-, primary tumour- and LRRC-related factors and
      intention of the treatment for LRRC were determined. The impact of the identified
      predictive factors on prognosis after treatment with curative intent was also
      assessed. RESULTS: A total of 426 patients were included in the study, of whom
      149 (35.0 per cent) received treatment with curative intent. Factors
      significantly associated with treatment of the LRRC with palliative intent were
      primary surgery with abdominoperineal resection (odds ratio (OR) 5.16, 95 per
      cent c.i. 2.97 to 8.97), age at diagnosis of LRRC at least 80 years (OR 4.82,
      2.37 to 9.80), symptoms at diagnosis (OR 2.79, 1.56 to 5.01) and non-central
      location of the LRRC (OR 1.79, 1.15 to 2.79). The overall 5-year survival rate
      was 8.9 per cent for all patients and 23.1 per cent among those treated with
      curative intent. In patients treated with curative intent, factors associated
      with increased risk of death were age 80 years or more (hazard ratio (HR) 2.44,
      95 per cent c.i. 1.55 to 3.86), presence of symptoms (HR 1.92, 1.20 to 3.05), non
      central tumour location (HR 1.51, 1.01 to 2.26) and presence of hydronephrosis
      (HR 2.02, 1.18 to 3.44). CONCLUSION: Non-central location of the LRRC, presence
      of symptoms and age at least 80 years at diagnosis of the LRRC were associated
      with treatment with palliative intent.

PMID- 29023632
TI  - Heterogeneous reciprocal graphical models.
AB  - We develop novel hierarchical reciprocal graphical models to infer gene networks
      from heterogeneous data. In the case of data that can be naturally divided into
      known groups, we propose to connect graphs by introducing a hierarchical prior
      across group-specific graphs, including a correlation on edge strengths across
      graphs. Thresholding priors are applied to induce sparsity of the estimated
      networks. In the case of unknown groups, we cluster subjects into subpopulations
      and jointly estimate cluster-specific gene networks, again using similar
      hierarchical priors across clusters. We illustrate the proposed approach by
      simulation studies and three applications with multiplatform genomic data for
      multiple cancers.

PMID- 29023633
TI  - BDNF and BMI effects on brain structures of bipolar offspring: results from the
      global mood and brain science initiative.
AB  - OBJECTIVE: To compare brain-derived neurotrophic factor (BDNF) levels between
      offspring of individuals with bipolar disorders (BD) and healthy controls (HCs)
      and investigate the effects of BDNF levels and body mass index (BMI) on brain
      structures. METHOD: Sixty-seven bipolar offspring and 45 HCs were included (ages
      8-28). Structural images were acquired using 3.0 Tesla magnetic resonance
      imaging. Serum BDNF levels were measured using enzyme-linked immunosorbent assay.
      Multivariate and univariate analyses of covariance were conducted. RESULTS:
      Significantly higher BDNF levels were observed among bipolar offspring, relative
      to HCs (P > 0.025). Offspring status moderated the association between BDNF and
      BMI (F1 =4.636, P = 0.034). After adjustment for relevant covariates, there was a
      trend for a significant interaction of group and BDNF on neuroimaging parameters
      (Wilks'lambda F56,94 =1.463, P = 0.052), with significant effects on cerebellar
      white matter and superior and middle frontal regions. Brain volume and BDNF were
      positively correlated among HCs and negatively correlated among bipolar
      offspring. Interactions between BDNF and BMI on brain volumes were non
      significant among HCs (Wilks'lambda F28,2 =2.229, P = 0.357), but significant
      among bipolar offspring (Wilks'lambda F28,12 =2.899, P = 0.028). CONCLUSION:
      Offspring status and BMI moderate the association between BDNF levels and brain
      structures among bipolar offspring, underscoring BDNF regulation and
      overweight/obesity as key moderators of BD pathogenesis.

PMID- 29023634
TI  - Improved knowledge of and difficulties in palliative care among physicians during
      2008 and 2015 in Japan: Association with a nationwide palliative care education
      program.
AB  - BACKGROUND: Palliative care education for health care professionals is a key
      element in improving access to quality palliative care. The Palliative Care
      Emphasis Program on Symptom Management and Assessment for Continuous Medical
      Education (PEACE) was designed to provide educational opportunities for all
      physicians in Japan. As of 2015, 57,764 physicians had completed it. The
      objective of this study was to estimate the effects of the program. METHODS: This
      study was an analysis of 2 nationwide observational studies from 2008 and 2015.
      We conducted 2 questionnaire surveys for representative samples of physicians.
      The measurements used were the Palliative Care Knowledge Test (range, 0-100) and
      the Palliative Care Difficulties Scale (range, 1-4). Comparisons were made with
      the unpaired Student t test and with a multivariate linear regression model using
      2 cohorts and a propensity score-matched sample. RESULTS: This study analyzed a
      total of 48,487 physicians in 2008 and a total of 2720 physicians in 2015.
      Between 2008 and 2015, physicians' knowledge and difficulties significantly
      improved on the Palliative Care Knowledge Test with total scores of 68 and 78,
      respectively (P < .001; effect size, 0.40) and on the Palliative Care
      Difficulties Scale with total scores of 2.65 and 2.49, respectively (P < .001;
      effect size, 0.29). Propensity-score matching resulted in 619 untrained
      physicians matched to 619 trained physicians, and physicians who trained with the
      PEACE program had a higher knowledge score (74 vs 86; P < .001; effect size,
      0.64) and a lower difficulties score (2.6 vs 2.3; P < .001; effect size, 0.42).
      CONCLUSIONS: Physicians' knowledge of and difficulties with palliative care
      improved on a national level. The PEACE program may have contributed to these
      improvements. Cancer 2018;124:626-35. (c) 2017 American Cancer Society.

PMID- 29023635
TI  - Intermittent gait disturbance in idiopathic normal pressure hydrocephalus.
AB  - OBJECTIVES: We identified intermittent gait disturbance (IGD) observed in the
      mild stage of idiopathic normal pressure hydrocephalus (iNPH). The first purpose
      of this study was to clarify the temporal gait profile of IGD during long
      distance gait. The second purpose was to confirm the difference in treatment
      effect after cerebrospinal fluid (CSF) shunting in patients with and without IGD.
      MATERIALS AND METHODS: Fourteen consecutive iNPH patients with mild gait
      disturbance with a timed up-and-go (TUG) of <20 seconds were prospectively
      enrolled in the study. All patients were asked "Do you experience gait difficulty
      after over five minutes of walking?" Seven "yes" patients formed the IGD group,
      and seven "no" patients formed the persistent gait disturbance (PGD) group. One
      day before and 7 days after CSF shunting, gait function was evaluated by the 6
      minute walk test (6MWT) and TUG. RESULTS: Preoperatively, all patients in the IGD
      group demonstrated features of IGD during the 6MWT, characterized by a
      progressive pattern of decreased gait speed and step length with increased
      cadence and absence of leg pain. Post-operatively, these features of IGD improved
      in all patients. In the PGD group, preoperative walking did not significantly
      worsen during the 6MWT and did not significantly change 7 days after treatment.
      Improvement of gait symptoms 1 week after CSF shunting could be detected with
      6MWT instead of TUG. CONCLUSIONS: Intermittent gait disturbance is not a rare
      symptom in mild stage of iNPH and may serve as an important clinical diagnostic
      marker for identifying mild iNPH patients.

PMID- 29023636
TI  - Revised Functional Capacity Index as a predictor of outcome following injury.
AB  - BACKGROUND: Assessment of functional outcomes in survivors of severe injury is an
      identified priority for trauma systems. The predictive Functional Capacity Index
      (pFCI) within the 2008 Abbreviated Injury Scale dictionary (pFCI08) offers a
      widely available tool for predicting functional outcomes without requiring long
      term follow-up. This study aimed to assess the 12-month functional outcome
      predictions of pFCI08 in a major trauma population, and to test the assumptions
      made by its developers to ensure population homogeneity. METHODS: Patients with
      major trauma from Victoria, Australia, were followed up using routine telephone
      interviews. Assessment of survivors 12 months after injury included the Glasgow
      Outcome Scale - Extended (GOS-E). kappa scores were used to measure agreement
      between pFCI08 and assessed GOS-E scores. RESULTS: Of 20 098 patients with severe
      injury, 12 417 had both pFCI08 and GOS-E scoring available at 12 months. The
      quadratic weighted kappa score across this population was 0.170; this increased
      to 0.244 in the subgroup of 1939 patients who met all pFCI assumptions. However,
      expanding the age range used in this group did not significantly affect kappa
      scores until patients over the age of 70 years were included. DISCUSSION: The
      pFCI08 has only a slight agreement with outcomes following major trauma. However,
      the age limits in the pFCI development assumptions are unnecessarily restrictive.
      The pFCI08 may be able to contribute to future systems predicting functional
      outcomes following severe injury, but is likely to explain only a small
      proportion of the variability in patient outcomes.

PMID- 29023637
TI  - AnthropMMD: An R package with a graphical user interface for the mean measure of
      divergence.
AB  - The mean measure of divergence is a dissimilarity measure between groups of
      individuals described by dichotomous variables. It is well suited to datasets
      with many missing values, and it is generally used to compute distance matrices
      and represent phenograms. Although often used in biological anthropology and
      archaeozoology, this method suffers from a lack of implementation in common
      statistical software. A package for the R statistical software, AnthropMMD, is
      presented here. Offering a dynamic graphical user interface, it is the first one
      dedicated to Smith's mean measure of divergence. The package also provides
      facilities for graphical representations and the crucial step of trait selection,
      so that the entire analysis can be performed through the graphical user
      interface. Its use is demonstrated using an artificial dataset, and the impact of
      trait selection is discussed. Finally, AnthropMMD is compared to three other free
      tools available for calculating the mean measure of divergence, and is proven to
      be consistent with them.

PMID- 29023638
TI  - The optimal regimen of brentuximab vedotin for CD30+ cutaneous lymphoma: are we
      there yet?

PMID- 29023639
TI  - An anatomical and mechanical analysis of the douc monkey (genus Pygathrix), and
      its role in understanding the evolution of brachiation.
AB  - OBJECTIVES: Pygathrix is an understudied Asian colobine unusual among the Old
      World monkeys for its use of arm-swinging. Little data exists on the anatomy and
      mechanics of brachiation in this genus. Here, we consider this colobine to gain
      insight into the parallel evolution of suspensory behavior in primates. MATERIALS
      AND METHODS: This study compares axial and appendicular morphological variables
      of Pygathrix with other Asian colobines. Additionally, to assess the functional
      consequences of Pygathrix limb anatomy, kinematic and kinetic data during arm
      swinging are included to compare the douc monkey to other suspensory primates
      (Ateles and Hylobates). RESULTS: Compared to more pronograde species, Pygathrix
      and Nasalis share morphology consistent with suspensory locomotion such as its
      narrower scapulae and elongated clavicles. More distally, Pygathrix displays a
      gracile humerus, radius, and ulna, and shorter olecranon process. During
      suspensory locomotion, Pygathrix, Ateles, and Hylobates all display mechanical
      convergence in limb loading and movements of the shoulder and elbow, but
      Pygathrix uses pronated wrist postures that include substantial radial deviation
      during arm-swinging. DISCUSSION: The adoption of arm-swinging represents a major
      shift within at least three anthropoid clades and little data exist about its
      transition. Across species, few mechanical differences are observed during arm
      swinging. Apparently, there are limited functional solutions to the challenges
      associated with moving bimanually below branches, especially in more proximal
      forelimb regions. Morphological data support this idea that the Pygathrix distal
      forelimb differs from apes more than its proximal end. These results can inform
      other studies of ape evolution, the pronograde to orthograde transition, and the
      convergent ways in which suspensory locomotion evolved in primates.

PMID- 29023640
TI  - Further consideration of the curvature of the Neandertal Femur.
AB  - OBJECTIVES: Neandertal femora are particularly known for having a marked sagittal
      femoral curvature. This study examined femoral curvature in Neandertals in
      comparison to a modern human population from Belgium by the use of three
      dimensional (3D) quadric surfaces modeled from the bone surface. 3D models
      provide detailed information and enabled femoral curvature to be analyzed in
      conjunction with other morphological parameters. MATERIALS AND METHODS: 3D models
      were created from CT scans of 75 modern human femora and 7 Neandertal femora.
      Quadric surfaces (QS) were created from the triangulated surface vertices in all
      areas of interest (neck, head, diaphyseal shaft, condyles) extracted from
      previously placed anatomical landmarks. The diaphyseal shaft was divided into
      five QS shapes and curvature was measured by degrees of difference between QS
      shapes. Each bone was placed in a local coordinate system enabling each bone to
      be analyzed in the same way. RESULTS: The use of 3D quadric surface fitting
      allowed the distribution of curvature with similarly curved femora to be analyzed
      and the different patterns of curvature between the two groups to be determined.
      The Neandertals were shown to have a higher degree of femoral curvature and a
      more distal point of femoral curvature than the modern human population from
      Belgium. CONCLUSIONS: Morphological aspects of the Neandertal femur are different
      from this modern human population although mainly seem unrelated to femoral
      curvature. The relative lack of correlations with other femoral bony
      morphological factors suggests femoral curvature variations may be related to
      other aspects.

PMID- 29023641
TI  - Comparison of injection-site reactions between the etanercept biosimilar SB4 and
      the reference etanercept in patients with rheumatoid arthritis from a phase III
      study.

PMID- 29023642
TI  - Hospital admission and surgical approach to tubal ectopic pregnancy in Australia
      2000 to 2014: A population-based study.
AB  - BACKGROUND: There are several accepted approaches to management of ectopic
      pregnancy, both surgical and non-surgical. When a surgical approach is used,
      there appears to be an equipoise between tubal preservation and removal. We
      sought to determine the patterns of surgical management of ectopic pregnancy in
      Australia since the year 2000. MATERIALS AND METHODS: Data regarding hospital
      admissions for ectopic pregnancy were extracted from the Australian Institute of
      Health and Welfare national procedural dataset for the years 2000-2013. Surgical
      procedures were classified as open or laparoscopic, and involving salpingotomy or
      salpingectomy (tubal removal). The results were stratified into age bands.
      RESULTS: Over the study period hospital admission rates for ectopic pregnancy
      rose in women under the age of 30, without an increase in surgical procedures,
      while the rate of surgical procedures fell in women in older age groups. Rates of
      management of ectopic pregnancy via laparotomy fell in all age groups, as did
      rates of tubal preservation. CONCLUSION: Since the year 2000 there have been
      changes in the management of ectopic pregnancy, with significant reductions in
      open surgery and tubal preservation.

PMID- 29023643
TI  - Improved survival of patients with melanoma brain metastases in the era of
      targeted BRAF and immune checkpoint therapies.
AB  - BACKGROUND: The development of brain metastases is common for systemic treatment
      failure in patients with melanoma and has been associated with a poor prognosis.
      Recent advances with BRAF and immune checkpoint therapies have led to improved
      patient survival. Herein, the authors evaluated the risk of de novo brain
      metastases and survival among patients with melanoma brain metastases (MBM) since
      the introduction of more effective therapies. METHODS: Patients with unresectable
      AJCC stage III/IV melanoma who received first-line systemic therapy at Moffitt
      Cancer Center between 2000 and 2012 were identified. Data were collected
      regarding patient characteristics, stage of disease, systemic therapies, MBM
      status/management, and overall survival (OS). The risk of de novo MBM was
      calculated using a generalized estimating equation model and survival comparisons
      were performed using Kaplan-Meier and Cox proportional analyses. RESULTS: A total
      of 610 patients were included, 243 of whom were diagnosed with MBM (40%).
      Patients with MBM were younger, with a lower frequency of regional metastasis. No
      significant differences were noted with regard to sex, BRAF status, or
      therapeutic class. The risk of de novo MBM was found to be similar among patients
      treated with chemotherapy, biochemotherapy, BRAF-targeted therapy, ipilimumab,
      and anti-programmed cell death protein 1/programmed death-ligand 1 regimens. The
      median OS of patients with MBM was significantly shorter when determined from the
      time of first regional/distant metastasis but not when determined from the time
      of first systemic therapy. The median OS from the time of MBM diagnosis was 7.5
      months, 8.5 months, and 22.7 months, respectively, for patients diagnosed from
      2000 to 2008, 2009 to 2010, and 2011 to the time of last follow-up (P = .002).
      CONCLUSIONS: Brain metastases remain a common source of systemic treatment
      failure. The OS for patients with MBM has improved significantly. Further
      research into MBM prevention is needed. Cancer 2018;124:297-305. (c) 2017
      American Cancer Society.

PMID- 29023645
TI  - Higher cigarette pricing encourages older smokers to quit.

PMID- 29023646
TI  - Erythrokeratoderma: a manifestation associated with multiple types of ichthyoses
      with different gene defects.

PMID- 29023644
TI  - A two-stage model for wearable device data.
AB  - Recent advances of wearable computing technology have allowed continuous health
      monitoring in large observational studies and clinical trials. Examples of data
      collected by wearable devices include minute-by-minute physical activity proxies
      measured by accelerometers or heart rate. The analysis of data generated by
      wearable devices has so far been quite limited to crude summaries, for example,
      the mean activity count over the day. To better utilize the full data and account
      for the dynamics of activity level in the time domain, we introduce a two-stage
      regression model for the minute-by-minute physical activity proxy data. The model
      allows for both time-varying parameters and time-invariant parameters, which
      helps capture both the transition dynamics between active/inactive periods (Stage
      1) and the activity intensity dynamics during active periods (Stage 2). The
      approach extends methods developed for zero-inflated Poisson data to account for
      the high-dimensionality and time-dependence of the high density data generated by
      wearable devices. Methods are motivated by and applied to the Baltimore
      Longitudinal Study of Aging.

PMID- 29023647
TI  - Breast cancer risk associated with atypical hyperplasia and lobular carcinoma in
      situ initially diagnosed on core-needle biopsy.
AB  - BACKGROUND: Breast cancer risk estimates for atypical lesions are based primarily
      on case-control studies of patients with open biopsies. The authors report the
      cumulative breast cancer incidence after a core biopsy diagnosis of atypical
      hyperplasia (ductal or lobular) or lobular carcinoma in situ. METHODS: A cohort
      study with central pathology review was conducted on 393 patients who had core
      biopsy diagnoses of atypical hyperplasia and lobular carcinoma in situ from 1995
      through 2010. Follow-up was available for 255 of 264 patients (97%) at a median
      of 87 months (range, 3-236 months). RESULTS: There were 212 patients (54%) who
      were not upgraded on excision and had no personal history of breast cancer. Of
      these, 21 of 212 (9.9%) developed breast cancer, including 15 invasive
      carcinomas, 4 ductal carcinomas in situ, 1 pleomorphic lobular carcinoma in situ,
      and 1 unknown type. The prior core biopsy diagnoses were atypical ductal
      hyperplasia for 11 patients (52%) and atypical lobular hyperplasia/lobular
      carcinoma in situ in the remaining 10 patients (48%). The number of atypical foci
      in the core biopsy was not significantly associated with the subsequent
      development of breast cancer (P = .42). Of the 15 invasive carcinomas, 11 (73%)
      were ipsilateral, 11 (73%) were pathologic T1 tumors, 5 (33%) were pathologic N1
      tumors, 13 (87%) were estrogen receptor-positive, and 1 (7%) was amplified for
      human epidermal growth factor receptor 2. CONCLUSIONS: In patients who had an
      initial diagnosis of atypical hyperplasia or lobular carcinoma in situ on core
      biopsy, the 7-year cumulative breast cancer incidence was 9.9%. Most tumors were
      ipsilateral, stage I, estrogen receptor-positive, invasive carcinomas. The
      current data support close clinical and radiologic follow-up for more than 5
      years in this patient population. Cancer 2018;124:459-65. (c) 2017 American
      Cancer Society.

PMID- 29023650
TI  - The Hand Assessment of Infants: a new tool to understand early hand function in
      children at high risk of unilateral cerebral palsy.

PMID- 29023651
TI  - Relations between the American Medical Association, the American Therapeutic
      Society, and the American Society for Clinical Pharmacology and Therapeutics.

PMID- 29023648
TI  - Improvements in hospice utilization among patients with advanced-stage lung
      cancer in an integrated health care system.
AB  - BACKGROUND: Hospice, a patient-centered care system for those with limited life
      expectancy, is important for enhancing quality of life and is understudied in
      integrated health care systems. METHODS: This was a retrospective cohort study of
      21,860 decedents with advanced-stage lung cancer diagnosed from January 2007 to
      June 2013 in the national US Veterans Affairs Health Care System. Trends over
      time, geographic regional variability, and patient and tumor characteristics
      associated with hospice use and the timing of enrollment were examined.
      Multivariable logistic regression and Cox proportional hazards modeling were
      used. RESULTS: From 2007 to 2013, 70.3% of decedents with advanced-stage lung
      cancer were enrolled in hospice. Among patients in hospice, 52.9% were enrolled
      in the last month of life, and 14.7% were enrolled in the last 3 days of life.
      Hospice enrollment increased (adjusted odds ratio [AOR], 1.07; P < .001), whereas
      the mean time from the cancer diagnosis to hospice enrollment decreased by 65
      days (relative decrease, 32%; adjusted hazard ratio, 1.04; P < .001). Relative
      decreases in late hospice enrollment were observed in the last month (7%; AOR,
      0.98; P = .04) and last 3 days of life (26%; AOR, 0.95; P < .001). The Southeast
      region of the United States had both the highest rate of hospice enrollment and
      the lowest rate of late enrollment. Patient sociodemographic and lung cancer
      characteristics were associated with hospice enrollment. CONCLUSIONS: Among
      patients with advanced-stage lung cancer in the Veterans Affairs Health Care
      System, overall and earlier hospice enrollment increased over time. Considerable
      regional variability in hospice enrollment and the persistence of late enrollment
      suggests opportunities for improvement in end-of-life care. Cancer 2018;124:426
      33. (c) 2017 American Cancer Society.

PMID- 29023649
TI  - A Long-Term Effect of Perceptual Individuation Training on Reducing Implicit
      Racial Bias in Preschool Children.
AB  - This study tracked the long-term effect of perceptual individuation training on
      reducing 5-year-old Chinese children's (N = 95, Mage  = 5.64 years) implicit pro
      Asian/anti-Black racial bias. Initial training to individuate other-race Black
      faces, followed by supplementary training occurring 1 week later, resulted in a
      long-term reduction of pro-Asian/anti-Black bias (70 days). In contrast, training
      Chinese children to recognize White or Asian faces had no effect on pro
      Asian/anti-Black bias. Theoretically, the finding that individuation training can
      have a long-term effect on reducing implicit racial bias in preschoolers suggests
      that a developmentally early causal linkage between perceptual and social
      processing of faces is not a transitory phenomenon. Practically, the data point
      to an effective intervention method for reducing implicit racism in young
      children.

PMID- 29023652
TI  - Preface.

PMID- 29023653
TI  - The American Society for Clinical Pharmacology and Therapeutics: Its role in
      board certification in clinical pharmacology.

PMID- 29023654
TI  - The American Society for Clinical Pharmacology and Therapeutics: Programs to
      support education in clinical pharmacology.

PMID- 29023655
TI  - Annual meetings of the American Therapeutic Society and the American Society for
      Clinical Pharmacology and Therapeutics.

PMID- 29023656
TI  - The history of CLINICAL PHARMACOLOGY & THERAPEUTICS.

PMID- 29023657
TI  - Future of the American Society for Clinical Pharmacology and Therapeutics.

PMID- 29023658
TI  - Officers and award recipients.

PMID- 29023660
TI  - Financial history: 1970 to 1988.

PMID- 29023659
TI  - The relationships of the American Society for Clinical Pharmacology and
      Therapeutics to government.

PMID- 29023661
TI  - The American Society for Clinical Pharmacology and Therapeutics and the
      pharmaceutical industry.

PMID- 29023662
TI  - Research and the American Society for Clinical Pharmacology and Therapeutics.

PMID- 29023663
TI  - The founding, growth, and development.

PMID- 29023664
TI  - Discrimination and Ethnic-Racial Identity: Understanding Direction of Effects
      Using Within- and Between-Person Analyses.
AB  - Ethnic-racial identity (ERI) development and ethnic-racial discrimination are two
      salient experiences among adolescents in the United States. Despite growing
      awareness of the costs and benefits of these experiences individually, we know
      little about how they may influence one another. The current study examined
      competing hypotheses relating discrimination and components of ERI (i.e.,
      exploration, resolution, affirmation) among a sample of Mexican-origin adolescent
      mothers (N = 181; Mage at Wave 1 = 16.83, SD = 1.01) across six waves of data.
      Findings revealed that within-person changes in discrimination predicted
      subsequent ERI resolution and affirmation; however, ERI did not predict
      subsequent discrimination. Between-person effects of discrimination on
      affirmation were significant. Our findings underscore the importance of
      discrimination experiences in shaping Mexican-origin adolescent mothers'
      normative developmental competencies.

PMID- 29023665
TI  - Clinician's guide to genes associated with Rett-like phenotypes-Investigation of
      a Danish cohort and review of the literature.
AB  - The differential diagnostics in Rett syndrome has evolved with the development of
      next generation sequencing-based techniques and many patients have been diagnosed
      with other syndromes or variants in newly described genes where the associated
      phenotype(s) is yet to be fully explored. The term Rett-like refers to phenotypes
      with distinct overlapping features of Rett syndrome where the clinical criteria
      are not completely fulfilled. In this study we have combined a review of Rett
      like disorders with data from a Danish cohort of 35 patients with Rett-like
      phenotypes emphasizing the diagnostic overlap with Pitt-Hopkins syndrome,
      Cornelia de Lange syndrome with SMC1A variants, and epileptic encephalopathies,
      for example, due to STXBP1 variants. We also found a patient with a pathogenic
      variant in KCNB1, which has not been previously linked to a Rett-like phenotype.
      This study underlines the clinical and genetic heterogeneity of a Rett syndrome
      spectrum, and provides an overview of the Rett syndrome-related genes described
      to date, and hence serves as a guide for diagnosing patients with Rett-like
      phenotypes.

PMID- 29023666
TI  - Nutritional intervention and neurodevelopmental outcome in infants with suspected
      cerebral palsy: the Dolphin infant double-blind randomized controlled trial.
AB  - AIM: To investigate whether docosahexaenoic acid (DHA), choline, and uridine-5
      monophosphate (UMP) supplementation improves neurodevelopmental outcome in
      infants with suspected cerebral palsy (CP) versus a comparison group of children.
      METHOD: Infants aged 1 to 18 months with suspected CP were recruited from UK
      child development centres. Participants received daily treatment or control
      supplementation for 2 years (double-blind randomized control design).
      Stratification was by age, sex, predominant pattern of motor involvement (four
      limbs or other), and visual impairment (or not). The primary outcome was the
      cognitive composite score of the Bayley Scales of Infant and Toddler Development,
      Third Edition (CCS-Bayley-III). Secondary outcomes included language composite
      and motor composite scores of the Bayley Scales of Infant and Toddler
      Development, Third Edition (Bayley-III). RESULTS: Forty infants were recruited;
      35 began supplementation, 29 completed 1 to 2 years' supplementation. The
      treatment group CCS-Bayley-III was non-significantly higher than the comparison
      group (mean 77.7 [SD 19.2] and 72.2 [SD 19.8] respectively, mean modelled
      difference 4.4 [-2.8, 11.6]). The treatment group language scores, but not motor
      scores, were non-significantly higher than for the comparison group.
      INTERPRETATION: Most families found supplementation feasible. No statistically
      significant differences in neurodevelopmental outcome between the treatment and
      comparison groups were identified. Further investigation of neurodevelopmental
      outcome after supplementation with DHA, choline, and UMP of infants with
      suspected CP is warranted. WHAT THIS PAPER ADDS: This was the first trial of
      phosphatidylcholine precursor supplementation in infants with suspected cerebral
      palsy (CP). Families of infants with suspected CP found 2-year nutritional
      supplementation feasible. There was no statistically significant
      neurodevelopmental advantage for the treatment group versus the comparison group.
      However, treatment group cognitive and language advantage were of clinically
      meaningful magnitude.

PMID- 29023668
TI  - Ethnic Harassment and Immigrant Youth's Engagement in Violent Behaviors:
      Understanding the Risk Factors.
AB  - The present study aimed to examine whether ethnic harassment was related to
      violent behaviors among immigrant youth over time and to identify the risk
      factors. The sample comprised immigrant adolescents living in Sweden (N = 365;
      Mage  = 13.93, SD = 0.80). Results showed that the more youth were ethnically
      harassed, the more they engaged in violent acts over time. A separated identity
      significantly moderated the effect of ethnic harassment on youth's engagement in
      violent behaviors. Specifically, ethnic harassment positively predicted
      engagement in violent behaviors only at high levels of separated identity.
      Impulsivity and school ethnic composition did not act as moderators. The findings
      suggest that preventing violent behaviors among immigrant youth requires a focus
      on promoting positive interethnic relationships, and multicultural identity among
      immigrant youth.

PMID- 29023669
TI  - Fungi reduce preference and performance of insect herbivores on challenged
      plants.
AB  - Although insect herbivores and fungal pathogens frequently share the same
      individual host plant, we lack general insights in how fungal infection affects
      insect preference and performance. We addressed this question in a meta-analysis
      of 1,113 case studies gathered from 101 primary papers that compared preference
      or performance of insect herbivores on control vs. fungus challenged plants.
      Generally, insects preferred, and performed better on, not challenged plants,
      regardless of experimental conditions. Insect response to fungus infection
      significantly differed according to fungus lifestyle, insect feeding guild, and
      the spatial scale of the interaction (local/distant). Insect performance was
      reduced on plants challenged by biotrophic pathogens or endophytes but not by
      necrotrophic pathogens. For both chewing and piercing-sucking insects,
      performance was reduced on challenged plants when interactions occurred locally
      but not distantly. In plants challenged by biotrophic pathogens, both preference
      and performance of herbivores were negatively impacted, whereas infection by
      necrotrophic pathogens reduced herbivore preference more than performance and
      endophyte infection reduced only herbivore performance. Our study demonstrates
      that fungi could be important but hitherto overlooked drivers of plant-herbivore
      interactions, suggesting both direct and plant-mediated effects of fungi on
      insect's behavior and development.

PMID- 29023667
TI  - Postnatal reduction of tuberous sclerosis complex 1 expression in astrocytes and
      neurons causes seizures in an age-dependent manner.
AB  - OBJECTIVE: Epilepsy is one of the most prominent symptoms of tuberous sclerosis
      complex (TSC), a genetic disorder, and may be related to developmental defects
      resulting from impaired TSC1 or TSC2 gene function in astrocytes and neurons.
      Inactivation of the Tsc1 gene driven by a glial-fibrillary acidic protein (GFAP)
      promoter during embryonic brain development leads to widespread pathologic
      effects on astrocytes and neurons, culminating in severe, progressive epilepsy in
      mice (Tsc1GFAP-Cre mice). However, the developmental timing and cellular
      specificity relevant to epileptogenesis in this model has not been well defined.
      The present study evaluates the effect of postnatal Tsc1 gene inactivation on
      pathologic features of astrocytes and neurons and development of epilepsy.
      METHODS: An inducible Tsc1 knock-out mouse was created utilizing a tamoxifen
      driven GFAP-CreER line (Tsc1GFAP-CreER mice) with TSC1 reduction induced
      postnatally at 2 and 6 weeks of age, and compared to conventional Tsc1GFAP-Cre
      mice with prenatal TSC1 reduction. Western blotting, immunohistochemistry,
      histology, and video-electroencephalography (EEG) assessed mechanistic target of
      rapamycin (mTOR) pathway activation, astrogliosis, neuronal organization, and
      spontaneous seizures, respectively. RESULTS: Tsc1 gene inactivation at 2 weeks of
      age was sufficient to cause astrogliosis and mild epilepsy in Tsc1GFAP-CreER
      mice, but the phenotype was much less severe than that observed with prenatal
      Tsc1 gene inactivation in Tsc1GFAP-Cre mice. Both astrocytes and neurons were
      affected by prenatal and postnatal Tsc1 gene activation to a degree similar to
      the severity of epilepsy, suggesting that both cellular types may contribute to
      epileptogenesis. SIGNIFICANCE: These findings support a model in which the
      developmental timing of TSC1 loss dictates the severity of neuronal and glial
      abnormalities and resulting epilepsy.

PMID- 29023670
TI  - Bi-dimensional null model analysis of presence-absence binary matrices.
AB  - Comparing the structure of presence/absence (i.e., binary) matrices with those of
      randomized counterparts is a common practice in ecology. However, differences in
      the randomization procedures (null models) can affect the results of the
      comparisons, leading matrix structural patterns to appear either "random" or not.
      Subjectivity in the choice of one particular null model over another makes it
      often advisable to compare the results obtained using several different
      approaches. Yet, available algorithms to randomize binary matrices differ
      substantially in respect to the constraints they impose on the discrepancy
      between observed and randomized row and column marginal totals, which complicates
      the interpretation of contrasting patterns. This calls for new strategies both to
      explore intermediate scenarios of restrictiveness in-between extreme constraint
      assumptions, and to properly synthesize the resulting information. Here we
      introduce a new modeling framework based on a flexible matrix randomization
      algorithm (named the "Tuning Peg" algorithm) that addresses both issues. The
      algorithm consists of a modified swap procedure in which the discrepancy between
      the row and column marginal totals of the target matrix and those of its
      randomized counterpart can be "tuned" in a continuous way by two parameters
      (controlling, respectively, row and column discrepancy). We show how combining
      the Tuning Peg with a wise random walk procedure makes it possible to explore the
      complete null space embraced by existing algorithms. This exploration allows
      researchers to visualize matrix structural patterns in an innovative bi
      dimensional landscape of significance/effect size. We demonstrate the rational
      and potential of our approach with a set of simulated and real matrices, showing
      how the simultaneous investigation of a comprehensive and continuous portion of
      the null space can be extremely informative, and possibly key to resolving
      longstanding debates in the analysis of ecological matrices.

PMID- 29023671
TI  - Genetics in pulmonary arterial hypertension in a large homogeneous Japanese
      population.
AB  - Pulmonary arterial hypertension (PAH) is a rare but serious disease with a grave
      prognosis. Bone morphogenetic protein type 2 receptor (BMPR2) gene is a strong
      pathogenic factor for PAH. As a collaborative team from Kyorin University and
      Keio University in Japan, we have analyzed the BMPR2 gene in 356 probands and
      more than 50 family members, including secondary patients. Importantly, the study
      population is a racially, ethnically, and socially homogeneous population. In PAH
      patients, there is a high incidence of unique mutations in BMPR2, and several
      mutations are frequently observed in the Japanese population, suggesting that
      these common and recurring mutations may be highly pathogenic or have high
      penetrance, explaining why they are found frequently throughout the world. We
      have also mapped each breakpoint of exonic deletions/duplications and found that
      most break and rejoining points are in the Alu elements. Reviewing the
      distribution of the reported mutations on each exon of BMPR2 revealed that the
      number and frequency of mutations are imbalanced among exons. The penetrance of
      BMPR2 gene mutations was 3-fold higher in females than males. Full elucidation of
      BMPR2-mediated pathogenic mechanisms in PAH requires persistent efforts to
      achieve precision or individualized medicine as a therapeutic strategy for PAH.

PMID- 29023672
TI  - Expecting the Unexpected? Expectations for Future Success Among Adolescent First
      Time Offenders.
AB  - Adolescent first-time offenders demonstrate greater risk of continued offending,
      justice system contact, and high school dropout. The current study evaluates if
      optimistic expectations protect youth by reducing offending and improving school
      grades for 3 years following a first arrest (N = 1,165, Mage  = 15.29). This
      article also considers whether improved behavior raises expectations about the
      future and uses autoregressive latent trajectory modeling with structured
      residuals to examine the within-person cross-lagged associations between
      expectations and behavior. The results indicated that positive expectations
      reduce offending and improve grades, which are in turn associated with higher
      expectations. Although raising expectations may improve outcomes following an
      arrest, ensuring adolescents have the tools to meet their goals may be an
      effective way to raise expectations.

PMID- 29023673
TI  - Eppur Si Muove: ferritin is essential in modulating inflammation.
AB  - Ferritin, which was only discovered in the last century, has stirred a formidable
      debate. Ferritin has long been appreciated as a non-specific acute-phase
      reactant. Several years ago, we hypothesized the contributory role of ferritin as
      a pathogenic molecule rather than being a product of inflammation. The latest
      emerging evidence provides support to this notion. Such revelation provides a
      step forward towards the understanding of disease conditions associated with
      hyperferritinaemia, and hence provide new targets for treatment modalities.

PMID- 29023675
TI  - European Marketing Authorizations Granted Based on a Single Pivotal Clinical
      Trial: The Rule or the Exception?
AB  - A minimum of two positive, adequate, and well-controlled clinical trials has
      historically been the gold standard for providing substantial evidence to support
      regulatory approval of a new medicine. Nevertheless, the present analysis of
      European Marketing Authorizations granted between 2012 and 2016 showed that 45%
      of new active substances were approved based on a single pivotal clinical trial.
      For therapeutic areas such as oncology and cardiovascular diseases, approvals
      based on a single pivotal trial are the rule rather than the exception, whereas
      new medicines within the nervous system area were generally supported by two or
      more pivotal trials. While overall similar trends have been observed in the US,
      the recent US Food and Drug Administration approvals of nervous system medicines
      based on a single pivotal trial suggest that a case-by-case scientific evaluation
      of the totality of evidence is increasingly applied to facilitate faster access
      of new medicines to patients suffering from serious diseases.

PMID- 29023676
TI  - Neurocognitive problems in children with congenital cytomegalovirus infection.

PMID- 29023674
TI  - Reverse Translational Research of ABCG2 (BCRP) in Human Disease and Drug
      Response.
AB  - Reverse translational research takes a bedside-to-bench approach, using
      sophisticated basic research to explain the biological mechanisms behind observed
      clinical data. For transporters, which play a role in human disease and drug
      response, this approach offers a distinct advantage over the typical
      translational research, which often falters due to inadequate in vitro and
      preclinical animal models. Research on ABCG2, which encodes the Breast Cancer
      Resistance Protein, has benefited immensely from a reverse translational approach
      due to its broad implications for disease susceptibility and both therapeutic and
      adverse drug response. In this review, we describe the success of reverse
      translational research for ABCG2 and opportunities for further studies.

PMID- 29023677
TI  - Climate drives phenological reassembly of a mountain wildflower meadow community.
AB  - Spatial community reassembly driven by changes in species abundances or habitat
      occupancy is a well-documented response to anthropogenic global change, but
      communities can also reassemble temporally if the environment drives differential
      shifts in the timing of life events across community members. Much like spatial
      community reassembly, temporal reassembly could be particularly important when
      critical species interactions are temporally concentrated (e.g., plant-pollinator
      dynamics during flowering). Previous studies have documented species-specific
      shifts in phenology driven by climate change, implying that temporal reassembly,
      a process we term "phenological reassembly," is likely. However, few studies have
      documented changes in the temporal co-occurrence of community members driven by
      environmental change, likely because few datasets of entire communities exist. We
      addressed this gap by quantifying the relationship between flowering phenology
      and climate for 48 co-occurring subalpine wildflower species at Mount Rainier
      (Washington, USA) in a large network of plots distributed across Mt. Rainier's
      steep environmental gradients; large spatio-temporal variability in climate over
      the 6 yr of our study (including the earliest and latest snowmelt year on record)
      provided robust estimates of climate-phenology relationships for individual
      species. We used these relationships to examine changes to community co-flowering
      composition driven by 'climate change analog' conditions experienced at our sites
      in 2015. We found that both the timing and duration of flowering of focal species
      was strongly sensitive to multiple climatic factors (snowmelt, temperature, and
      soil moisture). Some consistent responses emerged, including earlier snowmelt and
      warmer growing seasons driving flowering phenology earlier for all focal species.
      However, variation among species in their phenological sensitivities to these
      climate drivers was large enough that phenological reassembly occurred in the
      climate change analog conditions of 2015. An unexpected driver of phenological
      reassembly was fine-scale variation in the direction and magnitude of climatic
      change, causing phenological reassembly to be most apparent early and late in the
      season and in topographic locations where snow duration was shortest (i.e., at
      low elevations and on ridges in the landscape). Because phenological reassembly
      may have implications for many types of ecological interactions, failing to
      monitor community-level repercussions of species-specific phenological shifts
      could underestimate climate change impacts.

PMID- 29023678
TI  - Reverse Translation in PBPK and QSP: Going Backwards in Order to Go Forward With
      Confidence.
AB  - Significant events have taken place shaping the recent industrialization of
      physiologically based pharmacokinetic in vitro-in vivo extrapolation (PBPK-IVIVE)
      use in drug development. Due to our knowledge gaps about drug-independent systems
      parameters, there are limitations in the use of purely IVIVE-based (bottom-up)
      approaches. This has encouraged combining the classical data analysis (top-down)
      with PBPK-IVIVE-linked models in order to optimize model parameters by taking
      advantage of observed clinical data. This concept, when initiated after clinical
      observations, can be viewed as "reverse translation," since it refers back to
      available systems information preclinical data before trying to describe the
      observations. This review demonstrates the advantages of such strategies in
      filling knowledge gaps and discusses the perceived hurdles in widening
      applications. It is paramount that no clinical data are assessed on their own,
      but in conjunction with other studies for that drug in different populations
      and/or other similar drugs in the same population.

PMID- 29023679
TI  - Explaining ecosystem multifunction with evolutionary models.
AB  - Ecosystem function is the outcome of species interactions, traits, and niche
      overlap - all of which are influenced by evolution. However, it is not well
      understood how the tempo and mode of niche evolution can influence ecosystem
      function. In evolutionary models where either species differences accumulate
      through random drift in a single trait or species differences accumulate through
      divergent selection among close relatives, we should expect that ecosystem
      function is strongly related to diversity. However, when strong selection causes
      species to converge on specific niches or when novel traits that directly affect
      function evolve in some clades but not others, the relationship between diversity
      and ecosystem function might not be very strong. We test these ideas using a
      field experiment that established plant mixtures with differing phylogenetic
      diversities and we measured ten different community functions. We show that some
      functions were strongly predicted by species richness and mean pairwise
      phylogenetic distance (MPD, a measure of phylogenetic diversity), including
      biomass production and the reduction of herbivore and pathogen damage in
      polyculture, while other functions had weaker (litter production and structural
      complexity) or nonsignificant relationships (e.g., flower production and
      arthropod abundance) with MPD and richness. However, these divergent results can
      be explained by different models of niche evolution. These results show that
      diversity-ecosystem function relationships are the product of evolution, but that
      the nature of how evolution influences ecosystem function is complex.

PMID- 29023680
TI  - First direct evidence of involvement of a homozygous loss-of-function variant in
      the EPS15L1 gene underlying split-hand/split-foot malformation.
AB  - Split-hand/split-foot malformation (SHFM) is a severe form of congenital limb
      deformity characterized by the absence of 1 or more digits and/or variable degree
      of median clefts of hands and feet. The present study describes an investigation
      of a consanguineous family of Pakistani origin segregating SHFM in an autosomal
      recessive manner. Human genome scan using SNP markers followed by whole exome
      sequencing revealed a frameshift deletion (c.409delA, p.Ser137Alafs*19) in the
      EPS15L1 gene located on chromosome 19p13.11. This is the first biallelic variant
      identified in the EPS15L1 gene underlying SHFM. Our findings report the first
      direct involvement of EPS15L1 gene in the development of human limbs.

PMID- 29023681
TI  - N-terminal S-acylation facilitates tonoplast targeting of the calcium sensor
      CBL6.
AB  - Protein S-acylation is important for many biological processes. It confers
      proteins with the ability to attach to the plasma membrane and the membranes
      confining the ER and Golgi compartments. Yet, the contribution of S-acylation to
      regulating and targeting lysosomal/vacuolar proteins remains largely enigmatic.
      Here, we report that vacuolar targeting of the calcium sensor calcineurin B-like
      protein 6 (CBL6) from Arabidopsis thaliana is brought about by S-acylation of N
      terminal cysteine residues. Our results suggest distinctions in mechanisms and
      efficiency of targeting between CBL6 and the previously characterized vacuolar
      targeted CBL2 protein. Moreover, we define which CBL-interacting protein kinases
      (CIPKs) could interact with CBL6 and observe a remarkable temperature dependence
      of CBL6/CIPK complex formation. Collectively, these findings indicate a common S
      acyla tion-dependent vacuolar membrane targeting pathway for proteins.

PMID- 29023683
TI  - Reducing reactive aggression in schoolchildren through child, parent, and
      conjoint parent-child group interventions: An efficacy study of longitudinal
      outcomes.
AB  - This study was the first to evaluate the effectiveness of three different group
      interventions to reduce children's reactive aggression based on the social
      information processing (SIP) model. In the first stage of screening, 3,734
      children of Grades 4-6 completed the Reactive-Proactive Aggression Questionnaire
      (RPQ) to assess their reactive and proactive aggression. Respondents with a total
      score of z >= 1 on the RPQ were shortlisted for the second stage of screening by
      qualitative interview. Interviews with 475 children were conducted to select
      those who showed reactive aggression featuring a hostile attributional bias.
      Finally, 126 children (97 males and 29 females) aged 8 to 14 (M = 9.71, SD =
      1.23) were selected and randomly assigned to one of the three groups: a child
      group, a parent group, and a parent-child group. A significant Time *
      Intervention effect was found for general and reactive aggression. The parent
      child group and child group showed a significant drop in general aggression and
      reactive aggression from posttest to 6-month follow-up, after controlling for
      baseline scores, sex, and age. However, the parent group showed no treatment
      effect: reactive aggression scores were significantly higher than those in the
      child group at 6-month follow-up. This study has provided strong evidence that
      children with reactive aggression need direct and specific treatment to
      reconstruct the steps of the SIP involving the selection and interpretation of
      cues. The intervention could help to prevent severe violent crimes at the later
      stage of a reactive aggressor.

PMID- 29023682
TI  - Short-term cytokine stimulation reveals regulatory T cells with down-regulated
      Foxp3 expression in human peripheral blood.
AB  - The identification of regulatory T cells (Treg cells) in human peripheral blood
      is an important tool in diagnosis, research, and therapeutic intervention. As
      compared to lymphoid tissues, the frequencies of circulating Treg cells
      identified as CD4+ CD25+ Foxp3+ are, however, low. We here show that many of
      these cells remain undetected due to transient down regulation of Foxp3, which
      rapidly decays in the absence of cytokine-mediated STAT5 signals. Short-term
      incubation of PBMCs or isolated CD4+ T cells, but not of lymph node cells, with
      IL-2, -7, or -15 more than doubles the frequency of Foxp3+ CD25+ among CD4+ T
      cells detectable by flow cytometry. This increase is not due to cell division but
      to upregulation of both proteins. At the same time, the uncovered Treg cells up
      regulate CD25 and down-regulate CD127, making them accessible to viable cell
      sorting. "Latent" Treg cells have a demethylated FOXP3 TSDR sequence, are
      enriched in naive, non-cycling cells, and are functional. The confirmation of our
      findings in RA and SLE patients shows the feasibility of uncovering latent Treg
      cells for immune monitoring in clinical settings. Finally, our results suggest
      that unmasking of latent Treg cells contributes to the increase in circulating
      CD4+ CD25+ Foxp3+ cells reported in IL-2 treated patients.

PMID- 29023684
TI  - Spot On?

PMID- 29023685
TI  - Summary statement on screening for prostate cancer in Europe.
AB  - The European Randomised Study of Screening for Prostate Cancer (ERSPC) showed
      that Prostate-Specific Antigen (PSA) based screening results in a significant
      prostate cancer mortality reduction. Although there are concerns on overdiagnosis
      and overtreatment, it has been shown that the benefits can outweigh the harms if
      screening is stopped in older ages to prevent overdiagnosis. A limited screening
      program (for example screening at ages 55-59 years), including active
      surveillance for men with low-risk tumors, can even be cost-saving, compared with
      testing in an opportunistic setting in the wrong ages, as currently in Europe.
      Further improvements are expected in the use of active surveillance and in
      discrimination between indolent and significant disease due to new biomarkers and
      magnetic resonance imaging. However, these future developments are no reason to
      postpone feasibility studies of high-quality PSA screening and reduce
      opportunistic testing at old ages.

PMID- 29023686
TI  - Body fatness at an early age and risk of colorectal cancer.
AB  - While there is convincing evidence that excess body fatness in adulthood is
      positively associated with colorectal cancer risk, the association between body
      fatness at an early age (<=30 years) and the risk of colorectal cancer has been
      equivocal. The present meta-analysis was performed to clarify this association.
      PubMed and Web of Science databases were searched for relevant studies that
      investigated this association. The risk estimates from each study were
      transformed into a continuous variable for each 5 kg/m2 increase in body mass
      index (BMI). A random effects model was used to calculate the summary relative
      risks (RRs) with 95% confidence intervals (CIs). A total of 15 observational
      studies (13 cohort studies and two case-control studies) were included in this
      meta-analysis. Each 5 kg/m2 increase in BMI was significantly associated with a
      13% (RR 1.13, 95% CI 1.08, 1.19), 17% (RR 1.17, 95% CI 1.09, 1.25) and 8% (RR
      1.08, 95% CI 1.04, 1.11) higher risk of colorectal cancer overall, in men, and in
      women, respectively. Substantial heterogeneity was observed across studies. Based
      on the anatomic subsite, each 5 kg/m2 increase in BMI was significantly
      associated with a 14% (RR 1.14, 95% CI 1.07, 1.22) higher risk of colon cancer,
      whereas no association (RR 1.03, 95% CI 0.95, 1.13) was observed with rectal
      cancer. In summary, body fatness at an early age may affect colon cancer risk
      later in life. Prevention of overweight and obesity in young individuals should
      be emphasized to prevent early-onset colon cancer attributed to excess body
      fatness.

PMID- 29023687
TI  - A guide for effective anatomical vascularization studies: useful ex vivo methods
      for both CT and MRI imaging before dissection.
AB  - The objective of this study was to develop a simple and useful injection protocol
      for imaging cadaveric vascularization and dissection. Mixtures of contrast agent
      and cast product should provide adequate contrast for two types of ex vivo
      imaging (MRI and CT) and should harden to allow gross dissection of the injected
      structures. We tested the most popular contrast agents and cast products, and
      selected the optimal mixture composition based on their availability and ease of
      use. All mixtures were first tested in vitro to adjust dilution parameters of
      each contrast agent and to fine-tune MR imaging acquisition sequences. Mixtures
      were then injected in 24 pig livers and one human pancreas for MR and computed
      tomography (CT) imaging before anatomical dissection. Colorized latex, gadobutrol
      and barite mixture met the above objective. Mixtures composed of copper sulfate
      (CuSO4 ) gadoxetic acid (for MRI) and iodine (for CT) gave an inhomogeneous
      signal or extravasation of the contrast agent. Agar did not harden sufficiently
      for gross dissection but appears useful for CT and magnetic resonance imaging
      (MRI) studies without dissection. Silicone was very hard to inject but achieved
      the goals of the study. Resin is particularly difficult to use but could replace
      latex as an alternative for corrosion instead of dissection. This injection
      protocol allows CT and MRI images to be obtained of cadaveric vascularization and
      anatomical casts in the same anatomic specimen. Post-imaging processing software
      allow easy 3D reconstruction of complex anatomical structures using this
      technique. Applications are numerous, e.g. surgical training, teaching methods,
      postmortem anatomic studies, pathologic studies, and forensic diagnoses.

PMID- 29023688
TI  - Developing nursing research in the United Arab Emirates: a narrative review.
AB  - AIM: This article identified, critically analysed and synthesized the literature
      on international nursing and midwifery research capacity building and standards.
      BACKGROUND: The United Arab Emirates is heavily dependent up on expatriate
      nurses. Only 4% of nurses working within the country are Emirati. The nation is
      therefore committed to developing nurses and nursing as a profession.
      INTRODUCTION: The United Arab Emirates' Nursing and Midwifery Council was formed
      in 2009 and initially focused on regulation, education and specialization. This
      review was undertaken to inform the work of the Council's newly established
      Scientific Research Sub-Committee. METHODS: A rapid narrative review was
      conducted using the Cumulative Index of Nursing and Allied Health Literature
      database, key words, Boolean operators, parameters and a journal-specific search.
      An inclusion/exclusion criterion was identified. RESULTS: The search provided 332
      articles with 45 included in the final review. The literature on nursing research
      'standards' and 'capacity building' is diverse and inconsistent across continents
      and in approaches. DISCUSSION: Nursing research has evolved to varying degrees
      across the globe. Nevertheless, irrespective of the locale, there are similar
      problems encountered in growing research, for example nursing faculty shortage,
      lack of collaborative research, funding. There are also specific challenges in
      the Middle East and North Africa region. LIMITATIONS: The review was constrained
      by time and access. CONCLUSION AND IMPLICATIONS FOR NURSING POLICY: There are
      specific challenges for the United Arab Emirates. However, the country is well
      placed to learn from the experiences of colleagues elsewhere. Time and commitment
      is required to build the solid foundations necessary to ensure robust, sustained
      growth. Identifying research capacity as both a process and outcome at the outset
      may also assist. Further, it may be prudent to consider initiating a Gulf Coast
      Countries' collaborative approach to building research capacity to harness scare
      resources and create a larger critical mass.

PMID- 29023689
TI  - Difference of lower airway microbiome in bilateral protected specimen brush
      between lung cancer patients with unilateral lobar masses and control subjects.
AB  - The functional role of respiratory microbiota has attracted an accumulating
      attention recently. However, the role of respiratory microbiome in lung
      carcinogenesis is mostly unknown. Our study aimed to characterize and compare
      bilateral lower airway microbiome of lung cancer patients with unilateral lobar
      masses and control subjects. Protected bronchial specimen brushing samples were
      collected from 24 lung cancer patients with unilateral lobar masses (paired
      samples from cancerous site and the contralateral noncancerous site) and 18
      healthy controls undergoing bronchoscopies and further analyzed by 16S rRNA
      amplicon sequencing. As results, significant decreases in microbial diversity
      were observed in patients with lung cancer in comparison to the controls, alpha
      diversity steadily declined from healthy site to noncancerous to cancerous site.
      Genus Streptococcus was significantly more abundant in cancer cases than the
      controls, while Staphylococcus was more abundant in the controls. The area under
      the curve of genus Streptococcus used to predict lung cancer was 0.693
      (sensitivity = 87.5%, specificity = 55.6%). The abundance of genus Streptococcus
      and Neisseria displayed an increasing trend whereas Staphylococcus and Dialister
      gradually declined from healthy to noncancerous to cancerous site. Collectively,
      lung cancer-associated microbiota profile is distinct from that found in healthy
      controls, and the altered cancer-associated microbiota is not restricted to tumor
      tissue. The genus Streptococcus was abundant in lung cancer patients and
      exhibited moderate classification potential. The gradual microbiota profile shift
      from healthy site to noncancerous to paired cancerous site suggested a change of
      the microenvironment associated with the development of lung cancer.

PMID- 29023690
TI  - The bony horncore of the common eland (Taurotragus oryx): composition and
      mechanical properties of a spiral fighting structure.
AB  - Horns are permanent structures projecting from the head of bovids, consisting of
      a bony horncore covered with a layer of skin and then a sheath of keratinous
      material showing variability of growth intensity based on nutrition. From the
      point of view of the horn's mechanical properties, the keratin sheath has been
      widely studied, but only a few studies have considered the complete structure of
      the horn and fewer studies have focused on the bony horncore and its
      characteristics. The latter showed the important role of the bony core, when
      cranial appendages are subject to mechanical stress (as happens during fighting).
      The mechanical properties of bone material, along with its mineral profile, are
      also important, because they can show effects of different factors, such as
      nutrition and mineral deficiencies in diet. For this reason, eight horncores of
      captive common eland male were sampled at four positions along the vertical axis
      of the horn. The main aim was to study variation in mechanical properties and the
      mineral content along the vertical axis of the horncores. We further analysed
      whether the spiral bony ridge present on eland horncores differs in any of the
      studied properties from adjacent parts of the horncore. In other antelopes,
      spiral ridges on the horns have been proposed to increase grip during wrestling
      between males. Cross-sections of the horncores were performed at four positions
      along the longitudinal axis and, for each position, two bone bars were extracted
      to be tested in impact and bending. Moreover, in the first sampling position (the
      closest position to the base) two bars were extracted from the spiralled bony
      area. The resulting fragments were used to measure ash content, bone density and
      mineral content. Results showed that horn bone decreased along the vertical axis,
      in ash (-36%), density (-32%), and in impact work 'U' (marginally significant but
      large effect: -48%). The concentration of several minerals decreased
      significantly (Mg, Cr, Mn and Tl by -33%, -25%, -31%, -43%, respectively) between
      the basal and the uppermost sampling site. The bone tissue of the horncore spiral
      compared with non-spiral bone of the same position showed a lower ash content
      (53% vs. 57%), Mg and Mn; in addition to showing approximately half values in
      work to peak force 'W', bending strength 'BS' and 'U', but not in Young's modulus
      of elasticity 'E'. In conclusion, similarly to the results in a totally different
      fighting bony structure, the antlers, the horncore of eland shows advantageous
      parameters in bone tissue of the base in respect to the tip, with higher values
      for mechanical properties, density and mineral profile. Moreover, the spiral bone
      tissue showed lower material mechanical properties. Probably the spiral tissue of
      the horn may have a role in deflecting potential cross-sectional fractures during
      wrestling. In addition, it may serve to improve the grip during wrestling, and we
      propose that it may also prevent risk of rotation of sheath with respect to
      internal bone not only in this, but also in other straight bovid horns.

PMID- 29023691
TI  - Anatomy and development of the extrahepatic biliary system in mouse and rat: a
      perspective on the evolutionary loss of the gallbladder.
AB  - The gallbladder is the hepatobiliary organ for storing and secreting bile fluid,
      and is a synapomorphy of extant vertebrates. However, this organ has been
      frequently lost in several lineages of birds and mammals, including rodents.
      Although it is known as the traditional problem, the differences in development
      between animals with and without gallbladders are not well understood. To address
      this research gap, we compared the anatomy and development of the hepatobiliary
      systems in mice (gallbladder is present) and rats (gallbladder is absent).
      Anatomically, almost all parts of the hepatobiliary system of rats are
      topographically the same as those of mice, but rats have lost the gallbladder and
      cystic duct completely. During morphogenesis, the gallbladder-cystic duct domain
      (Gb-Cd domain) and its primordium, the biliary bud, do not develop in the rat. In
      the early stages, SOX17, a master regulator of gallbladder formation, is positive
      in the murine biliary bud epithelium, as seen in other vertebrates with a
      gallbladder, but there is no SOX17-positive domain in the rat hepatobiliary
      primordia. These findings suggest that the evolutionary loss of the Gb-Cd domain
      should be translated simply as the absence of a biliary bud at an early stage,
      which may correlate with alterations in regulatory genes, such as Sox17, in the
      rat. A SOX17-positive biliary bud is clearly definable as a developmental module
      that may be involved in the frequent loss of gallbladder in mammals.

PMID- 29023693
TI  - Host effects on microbiota community assembly.
AB  - To what extent host-associated microbiota assembly is driven by host selection or
      simply by happenstance remains an open question in microbiome research. Here, we
      take a first step towards elucidating the relative importance of host selection
      on the establishing gut microbial community in an ecologically relevant organism.
      We presented germ-free bumblebee, Bombus terrestris, workers from 10 colonies
      with a "global" microbial species pool comprised of an equal mixture of the gut
      microbiota of all colonies. By means of 16S amplicon sequencing, we found that
      overall microbiota community composition was generally shifted between pool
      exposed workers compared to workers that naturally acquired their gut microbiota,
      but that the specific composition of the established microbiota also depended on
      colony identity (e.g. genetic background). Because the microbiota is protective
      against parasite infection in this system, variation in the filtering of a
      beneficial microbial community can have important consequences for host
      resistance and eventual co-evolution with parasites.

PMID- 29023692
TI  - Lower socioeconomic status is independently associated with shorter survival in
      Hodgkin Lymphoma patients-An analysis from the Brazilian Hodgkin Lymphoma
      Registry.
AB  - Socioeconomic status (SES) is a well-known determinant of outcomes in cancer. The
      purpose of this study was to analyze the impact of the SES on the outcomes of
      Hodgkin lymphoma (HL) patients from the Brazilian Prospective HL Registry. SES
      stratification was done using an individual asset/education-based household
      index. A total of 624 classical HL patients with diagnosis from January/2009 to
      December/2014, and treated with ABVD (doxorubicin, bleomycin, vinblastine and
      dacarbazine), were analyzed. The median follow-up was 35.6 months, and 33% were
      classified as lower SES. The 3-year progression- free survival (PFS) in higher
      and lower SES were 78 and 64% (p < 0.0001), respectively. The 3-year overall
      survival (OS) in higher and lower SES were 94 and 82% (p < 0.0001), respectively.
      Lower SES patients were more likely to be >= 60 years (16 vs. 8%, p = 0.003), and
      to present higher risk International Prognostic score (IPS) (44 vs. 31%, p =
      0.004) and advanced disease (71 vs. 58%, p = 0.003). After adjustments for
      potential confounders, lower SES remained independently associated with poorer
      survival (HR = 3.12 [1.86-5.22] for OS and HR = 1.66 [1.19-2.32] for PFS). The
      fatality ratio during treatment was 7.5 and 1.3% for lower and higher SES (p =
      0.0001). Infections and treatment toxicity accounted for 81% of these deaths. SES
      is an independent factor associated with shorter survival in HL in Brazil.
      Potential underlying mechanisms associated with the impact of SES are delayed
      diagnosis and poorer education. Educational and socio-economic support
      interventions must be tested in this vulnerable population.

PMID- 29023694
TI  - Adaptive self-organization in the embryo: its importance to adult anatomy and to
      tissue engineering.
AB  - The anatomy of healthy humans shows much minor variation, and twin-studies reveal
      at least some of this variation cannot be explained genetically. A plausible
      explanation is that fine-scale anatomy is not specified directly in a genetic
      programme, but emerges from self-organizing behaviours of cells that, for
      example, place a new capillary where it happens to be needed to prevent local
      hypoxia. Self-organizing behaviour can be identified by manipulating growing
      tissues (e.g. putting them under a spatial constraint) and observing an adaptive
      change that conserves the character of the normal tissue while altering its
      precise anatomy. Self-organization can be practically useful in tissue
      engineering but it is limited; generally, it is good for producing realistic
      small-scale anatomy but large-scale features will be missing. This is because
      self-organizing organoids miss critical symmetry-breaking influences present in
      the embryo: simulating these artificially, for example, with local signal
      sources, makes anatomy realistic even at large scales. A growing understanding of
      the mechanisms of self-organization is now allowing synthetic biologists to take
      their first tentative steps towards constructing artificial multicellular systems
      that spontaneously organize themselves into patterns, which may soon be extended
      into three-dimensional shapes.

PMID- 29023695
TI  - The biorhythm of human skeletal growth.
AB  - Evidence of a periodic biorhythm is retained in tooth enamel in the form of
      Retzius lines. The periodicity of Retzius lines (RP) correlates with body mass
      and the scheduling of life history events when compared between some mammalian
      species. The correlation has led to the development of the inter-specific Havers
      Halberg oscillation (HHO) hypothesis, which holds great potential for studying
      aspects of a fossil species biology from teeth. Yet, our understanding of if, or
      how, the HHO relates to human skeletal growth is limited. The goal here is to
      explore associations between the biorhythm and two hard tissues that form at
      different times during human ontogeny, within the context of the HHO. First, we
      investigate the relationship of RP to permanent molar enamel thickness and the
      underlying daily rate that ameloblasts secrete enamel during childhood. Following
      this, we develop preliminary research conducted on small samples of adult human
      bone by testing associations between RP, adult femoral length (as a proxy for
      attained adult stature) and cortical osteocyte lacunae density (as a proxy for
      the rate of osteocyte proliferation). Results reveal RP is positively correlated
      with enamel thickness, negatively correlated with femoral length, but weakly
      associated with the rate of enamel secretion and osteocyte proliferation. These
      new data imply that a slower biorhythm predicts thicker enamel for children but
      shorter stature for adults. Our results develop the intra-specific HHO hypothesis
      suggesting that there is a common underlying systemic biorhythm that has a role
      in the final products of human enamel and bone growth.

PMID- 29023696
TI  - Tumor-infiltrating tryptase+ mast cells predict unfavorable clinical outcome in
      solid tumors.
AB  - The prognostic role of tumor-infiltrating tryptase+ mast cells in human solid
      tumors remains controversial. Herein, we conducted a meta-analysis including 28
      published studies with 4224 patients identified from PubMed and EBSCO to assess
      the prognostic impact of tumor-infiltrating tryptase+ mast cells in human solid
      tumors. We found that tryptase+ mast cell infiltration significantly decreased
      overall survival (OS) and disease-free survival (DFS) in all types of solid
      tumors. In stratified analyses, tryptase+ mast cell infiltration was
      significantly associated with worse OS in non-small cell lung cancer,
      hepatocellular carcinoma and 5-year survival in colorectal cancer. And these
      cells were inversely associated with DFS in hepatocellular and colorectal cancer.
      In addition, high density of intratumoral tryptase+ mast cells significantly
      correlated with lymph node metastasis of solid tumor. In conclusion, Tryptase+
      mast cell infiltration leads to an unfavorable clinical outcome in solid tumors,
      implicating that it is a valuable biomarker for prognostic prediction for human
      solid malignances and targeting it may have a potential for effective treatment.

PMID- 29023697
TI  - Neoadjuvant radiation therapy for the management of myoepithelial carcinoma of
      the upper extremity.
AB  - Myoepithelial tumors of the soft tissue are a rare tumor displaying myoepithelial
      elements and lacking obvious ductal differentiation. The rarity of these
      precludes any evidence-based consensus regarding optimal management.
      Nevertheless, the current approach to these lesions begins with amputation or
      complete excision. The efficacy of neoadjuvant or adjuvant radiation therapy or
      chemotherapy has not been established. Here, we present the first report to the
      authors' knowledge of neoadjuvant radiation therapy for the treatment of this
      rare soft tissue neoplasm and review the management and outcomes of published
      cases of myoepithelial carcinoma. A patient with a soft tissue myoepithelial
      carcinoma that declined both amputation and chemotherapy was treated with
      neoadjuvant radiation therapy and wide surgical excision followed by a
      brachytherapy boost to the resected tumor bed. Neoadjuvant radiation therapy
      resulted in an excellent response with extensive treatment-related changes
      consisting predominantly of fibrosis, hyalinization and hemorrhage and only 10%
      residual viable myoepithelial carcinoma present in the surgical specimen.

PMID- 29023698
TI  - Decomposition of socioeconomic inequalities in preterm deliveries in Tehran,
      Iran.
AB  - OBJECTIVE: To investigate associations between economic inequality in preterm
      delivery. METHODS: The present secondary analysis included cross-sectional data
      collected in interviews with patients following delivery at 103 hospitals in
      Tehran, Iran, between July 6 and 21, 2015. Principal component analysis was used
      to measure the socioeconomic status of participants and the concentration index
      was used to measure inequalities in preterm delivery among patients of different
      socioeconomic status. RESULTS: Data were included from 5170 patients. The
      concentration index for preterm delivery was 0.087 (95% confidence interval 0.036
      0.134), indicating that preterm deliveries were concentrated among patients with
      higher socioeconomic status. Higher socioeconomic status (94%), younger maternal
      age (29%), younger paternal age (21%), and being a homemaker (17%) had the
      highest positive contributions to the measured inequalities in preterm
      deliveries; vaginal delivery (-58%) had the highest negative contribution.
      CONCLUSION: Preterm deliveries were distributed unequally among the study
      patients in Iran, and were concentrated among patients of higher socioeconomic
      status. Alongside future etiological studies, reproductive programs in Iran
      should focus on this population to redress the observed inequality.

PMID- 29023700
TI  - Teaching & Learning Tips 1: Teaching perspectives - an introduction.
AB  - Challenge: Clinical and research responsibilities often leave little or no time
      to plan thoughtful teaching encounters with trainees. This "Teaching & Learning
      Tips" series is designed to be an accessible guide for dermatologists who want to
      improve their teaching skills. It is comprised of 12 articles about how to
      enhance teaching in various settings informed by research about how people learn
      and expert-derived or data-driven best practices for teaching. The series begins
      with a review of principles to optimize learning in any setting, including
      cognitive load theory, active learning strategies, and the impact of motivation
      and emotion on learning. It transitions into a practical "how to" guide format
      for common teaching scenarios in dermatology, such as lecturing, case-based
      teaching, and teaching procedures, among others. Herein, we kickoff the series by
      unpacking assumptions about teaching and learning. What does it mean to teach and
      learn?

PMID- 29023701
TI  - Identification of novel homozygous SLURP1 mutation in a Javanese family with Mal
      de Meleda.
AB  - BACKGROUND: Mal de Meleda (OMIM# 248300; keratosis palmoplantaris transgrediens)
      is an autosomal recessive form of palmoplantar keratoderma, clinically
      characterized by sharp demarcated erythema and hyperkeratosis of the palms and
      soles that progress with age and extend to the dorsal aspects of the hands and
      feet. The mal de Meleda is caused by mutations in the SLURP1 gene that encodes
      secreted lymphocyte antigen 6/urokinase-type plasminogen receptor-related protein
      1 (SLURP1). To date no reported cases from Indonesia. The aims of the study were
      to describe the typical features of mal de Meleda cases in a Javanese family in
      Indonesia and identify the mutation in the ARS B gene which encodes SLURP1.
      PATIENTS AND METHODS: In this study, three Javanese patients, siblings from
      nonconsanguineous nonaffected parents, presented with classical symptoms of mal
      de Meleda. Genetic analysis screening SLURP1 gene was conducted for the specimens
      from the patients and other family members. RESULTS: A novel homozygous three
      nucleotide deletion in exon 3, i.e. c.271-273TCTdel, was identified in the
      patients. Subcloning and sequencing revealed both parents (I.2 and I.3) and one
      of the father's siblings (I.1) carry heterozygous c.271-273TCTdel, while the
      other father's sibling (I.2), the mother's sister (I.4), and a healthy control
      matched the ethnicity of the family, showing normal sequence of the entire
      SLURP1. CONCLUSION: This is the first mal de Meleda case of Javanese ethnicity to
      be documented, and the unique mutation has not previously been reported. The
      finding supports the notion that despite the rarity, SLURP1 mutation causing mal
      de Meleda is ubiquitous.

PMID- 29023699
TI  - Using host species traits to understand the consequences of resource provisioning
      for host-parasite interactions.
AB  - Supplemental food provided to wildlife by human activities can be more abundant
      and predictable than natural resources, and subsequent changes in wildlife
      ecology can have profound impacts on host-parasite interactions. Identifying
      traits of species associated with increases or decreases in infection outcomes
      with resource provisioning could improve assessments of wildlife most prone to
      disease risks in changing environments. We conducted a phylogenetic meta-analysis
      of 342 host-parasite interactions across 56 wildlife species and three broad
      taxonomic groups of parasites to identify host-level traits that influence
      whether provisioning is associated with increases or decreases in infection. We
      predicted dietary generalists that capitalize on novel food would show greater
      infection in provisioned habitats owing to population growth and food-borne
      exposure to contaminants and parasite infectious stages. Similarly, species with
      fast life histories could experience stronger demographic and immunological
      benefits from provisioning that affect parasite transmission. We also predicted
      that wide-ranging and migratory behaviours could increase infection risks with
      provisioning if concentrated and non-seasonal foods promote dense aggregations
      that increase exposure to parasites. We found that provisioning increased
      infection with bacteria, viruses, fungi and protozoa (i.e. microparasites) most
      for wide-ranging, dietary generalist host species. Effect sizes for ectoparasites
      were also highest for host species with large home ranges but were instead lowest
      for dietary generalists. In contrast, the type of provisioning was a stronger
      correlate of infection outcomes for helminths than host species traits. Our
      analysis highlights host traits related to movement and feeding behaviour as
      important determinants of whether species experience greater infection with
      supplemental feeding. These results could help prioritize monitoring wildlife
      with particular trait profiles in anthropogenic habitats to reduce infectious
      disease risks in provisioned populations.

PMID- 29023703
TI  - Use of Multi-Intake Temporal Dominance of Sensations (TDS) to Evaluate the
      Influence of Wine on Cheese Perception.
AB  - : Even if wine and cheese have long been consumed together, there is little
      sensory evidence on how wine can influence the perception of cheese. In this work
      4 cheeses were dynamically characterized in terms of dominant sensations without
      and with wine consumption in between intakes. The tasting protocol was based on
      multi-intake temporal dominance of sensations (TDS) coupled with hedonic rating.
      Frequent wine and cheese consumers (n = 31) evaluated 4 cheeses (Epoisses,
      Chaource, and 2 different Comte) over 3 consecutive bites. In the following
      sessions they performed the same task, but taking sips of wine (rose Riceys,
      white Burgundy, red Burgundy, and red Beaujolais) between bites. All cheese-wine
      combinations were tasted over 4 sessions. TDS data were analyzed in terms of
      attribute duration of dominance by ANOVA, MANOVA, and canonical variate analysis.
      Results showed that wine consumption had an impact (P < 0.1) on dominance
      duration of attributes of cheeses, particularly on salty and some aromatic notes.
      But, as opposed to a previous work done by the same team, wine had no impact on
      the preference of cheese; this stayed constant under all the evaluating
      conditions. PRACTICAL APPLICATION: This paper aims to validate an innovative
      protocol on dynamic sensory data acquisition in which consumers evaluate the
      impact of a beverage (wine) on a solid food (cheese). This protocol is
      complementary to a previous one presented in this journal, where the effect of
      cheese was tested on wine. Together they make up an interesting approach towards
      developing a new tool for the food sector to better understand the impact of one
      food product on another. This could lead to a better description of a whole meal,
      something which is still missing in sensory science.

PMID- 29023704
TI  - GABAA receptor subunits in the human amygdala and hippocampus:
      Immunohistochemical distribution of 7 subunits.
AB  - GABAergic neurotransmission in the amygdala contributes to the regulation of
      emotional processes in anxiety, stress, reward, mnestic functions, addiction, and
      epilepsy. Species-specific differences in the distribution and composition of
      GABAA receptors may account for distinct effects and side-effects of GABAergic
      agents. However, data on the distribution and composition of GABAA receptors in
      the human amygdala are lacking. Here, the expression of GABAA receptor subunits
      alpha1, alpha2, alpha3, alpha5, beta2, beta2/3, and gamma2 was studied in the
      human amygdala using immunohistochemistry. Hippocampi were evaluated as a
      reference structure. Neuronal counts and field fraction analyses were performed,
      and subcellular expression of GABAA receptor subunits was analyzed
      semiquantitatively. In the amygdala, field fraction analyses showed the highest
      alpha1 expression in the lateral nucleus (La), whereas alpha3 was prominent in
      intercalated nuclei (IC), and alpha5 and gamma2 in the cortical nuclei, and
      amygdalo-hippocampal/parahippocampal-amygdala transition areas. In the
      hippocampus, alpha1 and alpha3 were accentuated in the dentate gyrus, CA1 region,
      and subiculum, whereas alpha5 expression was rather uniform. In both regions,
      alpha2 was homogenously distributed, and the two beta subunits and gamma2 showed
      faint immunostaining. The intensity of subunit expression also varied in the
      neuropil, neuronal somata, and/or cellular processes in the subregions. GABAA
      receptors containing subunit alpha1, showing the strongest expression in the La,
      and alpha3, with the strongest expression in the IC and subiculum, could be
      targets for treating amygdala-related disorders. Differences in GABAA receptor
      subunit expression between the human and rodent amygdala should be taken into
      consideration when developing subunit-selective drugs.

PMID- 29023705
TI  - Larval fish collected from sound-scattering layers in an offshore tropical area.
AB  - The composition of the larval fish assemblage in the sound-scattering layer of
      the continental shelf waters off the coast of south-eastern Brazil (12 and 22
      degrees  S), a research project that is part of the Brazilian programme Avaliacao
      do Potencial Sustentavel de Recursos Vivos na Zona Economica Exclusiva (REVIZEE),
      is described. Samples were collected during daylight hours and at dusk at five
      oceanographic stations in the winter of 1999 using an Isaacs-Kidd Midwater Trawl
      (IKMT). The oceanographic stations were chosen based on the detection of plankton
      layers by acoustic observation. A total of 2192 larval fish were identified,
      comprising 52 families and 62 species. Maurolicus stehmanni (Sternoptychidae) was
      the most abundant species found within the study area, comprising 18.5% of all
      identified larvae, followed by Psilotris celsus (Gobiidae) at 10.9%.

PMID- 29023708
TI  - Go with the immunological flow - Guidelines for flow cytometry.

PMID- 29023711
TI  - Alteration of sphingolipid metabolism as a putative mechanism underlying LPS
      induced BBB disruption.
AB  - Septic encephalopathy with confusion and agitation occurs early during sepsis and
      contributes to the severity of the disease. A decrease in the sphingosine-1
      phosphate (S1P) blood levels has been shown in patients and in animal models of
      sepsis. The lipid mediator S1P is known to be involved in endothelial barrier
      function in a context-dependent manner. We utilized lipopolysaccharide (LPS)
      injected mice as a model for septic encephalopathy and first performed tracer
      permeability assays to assess the blood-brain barrier (BBB) breakdown in vivo. At
      time points corresponding to the BBB breakdown post LPS injection, we aimed to
      characterize the regulation of the sphingolipid signaling pathway at the BBB
      during sepsis. We measured sphingolipid concentrations in blood, in mouse brain
      microvessels (MBMVs), and brain tissue. We also analyzed the expression of S1P
      receptors, transporters, and metabolizing enzymes in MBMVs and brain tissue.
      Primary mouse brain microvascular endothelial cells (MBMECs) were isolated to
      evaluate the effects of LPS on transendothelial electrical resistance (TEER) as a
      measure of permeability in vitro. We observed a relevant decrease in S1P levels
      after LPS injection in all three compartments (blood, MBMVs, brain tissue) that
      was accompanied by an increased expression of the S1P receptor type 1 and of
      sphingosine kinase 1 on one hand and of the S1P degrading enzymes lipid phosphate
      phosphatase 1 (LPP1) and S1P phosphatase 1 on the other hand, as well as a down
      regulation of sphingosine kinase 2. Application of LPS to a monolayer of primary
      MBMECs did not alter TEER, but serum from LPS-treated mice lead to a breakdown of
      the barrier compared to serum from vehicle-treated mice. We observed profound
      alterations of the sphingolipid metabolism at the BBB after LPS injection that
      point toward a therapeutic potential of drugs interfering with this pathway as
      novel approach for the detrimental overwhelming immune response in sepsis. Read
      the Editorial Highlight for this article on page 115. Cover Image for this Issue:
      doi. 10.1111/jnc.14161.

PMID- 29023712
TI  - The microstructure, local indium composition and photoluminescence in green
      emitting InGaN/GaN quantum wells.
AB  - In this work, we analyse the microstructure and local chemical composition of
      green-emitting Inx Ga1-x N/GaN quantum well (QW) heterostructures in correlation
      with their emission properties. Two samples of high structural quality grown by
      metalorganic vapour phase epitaxy (MOVPE) with a nominal composition of x = 0.15
      and 0.18 indium are discussed. The local indium composition is quantitatively
      evaluated by comparing scanning transmission electron microscopy (STEM) images to
      simulations and the local indium concentration is extracted from intensity
      measurements. The calculations point out that the measured indium fluctuations
      may be correlated to the large width and intensity decrease of the PL emission
      peak.

PMID- 29023713
TI  - Integrating clients' religion/spirituality in clinical practice: A comparison
      among social workers, psychologists, counselors, marriage and family therapists,
      and nurses.
AB  - OBJECTIVE: This study was designed to describe and compare five helping
      professions' views and behaviors regarding the integration of clients'
      religion/spirituality (RS) in clinical practice. METHOD: A cross-sectional design
      was used to survey 3,500 licensed clinical psychologists, nurses, marriage and
      family therapists (LMFTs), clinical social workers, and professional counselors
      across Texas. A total of 550 responded to this online survey, which included the
      Religious/Spiritually Integrated Practice Assessment Scale and background
      questions. RESULTS: Attitudes concerning the integration of clients' RS did not
      differ by profession and were fairly positive. However, differences emerged
      regarding self-efficacy, perceived feasibility, and behaviors, with LMFTs
      reporting the highest scores for these subscales. CONCLUSION: This is the first
      comparison of these five professions' attitudes, behaviors, perceived
      feasibility, and self-efficacy regarding integrating clients' RS. These
      encouraging results not only indicate helping professionals' openness to
      integrating clients' RS, but also highlight key differences in training, self
      efficacy, views of feasibility, and implementation.

PMID- 29023715
TI  - A new parameter of growth inhibition for cell proliferation assays.
AB  - Cell proliferation assays are performed by four decades to test the anti
      proliferative activity of natural products and synthetic compounds in cell
      cultures. In cancer research, they are widely employed to evaluate drug efficacy
      in in vitro tumor models, such as established cell lines, primary cultures, and
      recently developed three-dimensional tumor organoids. In this manuscript, we
      demonstrated that current employed parameters used by researchers to quantify in
      vitro growth inhibition, IC50 and GI50 , lead to a misinterpretation of results
      based on the exponential, and not linear, proliferation of the cells in culture.
      Therefore, we introduce a new parameter for the analysis of growth inhibition in
      cell proliferation assays, termed relative population doubling capacity, that can
      be employed to properly quantify the anti-proliferative activity of tested
      compounds and to compare drug efficacy between distinct cell models.

PMID- 29023714
TI  - In Vitro Assessment of Bioactivities of Lactobacillus Strains as Potential
      Probiotics for Humans and Chickens.
AB  - : Twelve previously isolated Lactobacillus strains were investigated for their in
      vitro bioactivities, including bile salt hydrolase (BSH), cholesterol-reducing
      and antioxidant activities, cytotoxic effects against cancer cells, enzyme
      activity, and biogenic amine production. Among them, only 4 strains showed
      relatively high BSH activity, whereas the rest exhibited low BSH activity. All 12
      strains showed cholesterol-reducing and antioxidant activities, especially in
      their intact cells, which in most of the cases, the isolated strains were
      stronger in these activities than the tested commercial reference strains. None
      of the tested strains produced harmful enzymes (beta-glucosidase and beta
      glucuronidase) or biogenic amines. Among the 12 strains, 3 strains were tested
      for their cytotoxic effects against 3 cancer cell lines, which exhibited strong
      cytotoxic effects, and they also showed selectivity in killing cancer cells when
      compared to normal cells. Hence, all 12 Lactobacillus strains could be considered
      good potential probiotic candidates because of their beneficial functional
      bioactivities. PRACTICAL APPLICATION: The Lactobacillus strains tested in this
      study could be considered good potential probiotic candidates for food/feed
      industry because of their beneficial functional bioactivities such as good
      cholesterol-reducing ability, high antioxidant activity, and good and selective
      cytotoxic effect against cancer cells.

PMID- 29023716
TI  - Production of Cornstarch Granules Enriched with Quercetin Liposomes by
      Aggregation of Particulate Binary Mixtures Using High Shear Process.
AB  - : Liposomes are colloidal structures capable of encapsulating, protecting, and
      releasing hydrophobic bioctives, as flavonoids. Quercetin is a flavonoid with
      high antioxidant activity that provides benefits to health. The wet-agglomeration
      processes in high-shear equipment are useful to produce granules from binary
      mixtures, obtaining a powder with homogeneous composition and without segregation
      or elutriation of fine particles. In this study, the binary mixtures containing
      microparticles of native cornstarch and nanoparticles of quercetin liposomes were
      aggregated in high-shear batches, using maltodextrin solution as binder agent.
      The cornstarch was enriched by agglomeration with 8%, 22%, and 30% (w/w) of
      quercetin-loaded lyophilized liposomes and the physical properties were
      evaluated. The moisture of all formulations showed similar values ranging from
      4.42% to 4.57%. The values of hygroscopicity (g adsorbed water/100 g of dry
      matter) indicated the lyophilized liposomes were able to decrease the capacity of
      the agglomerated cornstarch to absorb water, decreasing the possibility of
      microbiological contamination. The addition of quercetin-loaded lyophilized
      liposomes improved the flowability and turned the powder (agglomerated
      cornstarch) less cohesive. The pasting properties of enriched agglomerated
      cornstarch decreased the pasting temperature about 10  degrees C, and the
      cornstarch agglomerated with 8% (w/w) of quercetin-loaded lyophilized liposomes
      showed no significance difference in the peak viscosity. Agglomeration of
      cornstarch with more than 8% (w/w) lyophilized liposomes decreased the tendency
      of starch to retrograde, which is very interesting for food products which
      requires low levels of retrogradation of granules for their stability. PRACTICAL
      APPLICATION: This study is an unprecedent association of 2 technologies,
      nanoencapsulation and wet agglomeration, here used together to enrich cornstarch
      with quercetin. The agglomeration process was used to obtain granules of
      cornstarch, an ingredient extremely used in the food industry, enriched with
      quercetin-loaded lyophilized liposomes. The goals were both the improvement of
      the nutritional quality and the increase of the added value of the cornstarch.

PMID- 29023717
TI  - Recovery from the anatomical effects of long-term monocular deprivation in cat
      lateral geniculate nucleus.
AB  - Monocular deprivation (MD) imposed early in postnatal life elicits profound
      structural and functional abnormalities throughout the primary visual pathway.
      The ability of MD to modify neurons within the visual system is restricted to a
      so-called critical period that, for cats, peaks at about one postnatal month and
      declines thereafter so that by about 3 months of age MD has little effect.
      Recovery from the consequences of MD likewise adheres to a critical period that
      ends by about 3 months of age, after which the effects of deprivation are thought
      to be permanent and without capacity for reversal. The attenuation of plasticity
      beyond early development is a formidable obstacle for conventional therapies to
      stimulate recovery from protracted visual deprivation. In the current study we
      examined the efficacy of dark exposure and retinal inactivation with tetrodotoxin
      to promote anatomical recovery in the dorsal lateral geniculate nuclues (dLGN)
      from long-term MD started at the peak of the critical period. Whereas 10 days of
      dark exposure or binocular retinal inactivation were not better at promoting
      recovery than conventional treatment with reverse occlusion, inactivation of only
      the non-deprived (fellow) eye for 10 days produced a complete restoration of
      neuron soma size, and also reversed the significant loss of neurofilament protein
      within originally deprived dLGN layers. These results reveal a capacity for
      neural plasticity and recovery that is larger than anything previously observed
      following protracted MD in cat, and they highlight a possibility for alternative
      therapies applied at ages thought to be recalcitrant to recovery.

PMID- 29023718
TI  - Backscattered electron imaging and electron backscattered diffraction in the
      study of bacterial attachment to titanium alloy structure.
AB  - The application of secondary electron (SE) imaging, backscattered electron
      imaging (BSE) and electron backscattered diffraction (EBSD) was investigated in
      this work to study the bacterial adhesion and proliferation on a commercially
      pure titanium (cp Ti) and a Ti6Al4V alloy (Ti 64) with respect to substrate
      microstructure and chemical composition. Adherence of Gram-positive
      Staphylococcus epidermidis 11047 and Streptococcus sanguinis GW2, and Gram
      negative Serratia sp. NCIMB 40259 and Escherichia coli 10418 was compared on cp
      Ti, Ti 64, pure aluminium (Al) and vanadium (V). The substrate microstructure and
      the bacterial distribution on these metals were characterised using SE, BSE and
      EBSD imaging. It was observed that titanium alloy-phase structure, grain
      boundaries and grain orientation did not influence bacterial adherence or
      proliferation at microscale. Adherence of all four strains was similar on cp Ti
      and Ti 64 surfaces whilst inhibited on pure Al. This work establishes a
      nondestructive and straight-forward statistical method to analyse the
      relationship between microbial distribution and metal alloy structure.

PMID- 29023719
TI  - Natural variability and effects of cleaning and storage procedures on vertebral
      chemistry of the blacktip shark Carcharhinus limbatus.
AB  - Key methodological assumptions regarding the degree of natural variability and
      influence of sample handling and storage of elasmobranch vertebral chemistry were
      assessed using laser-ablation inductively coupled plasma mass spectrometry.
      Vertebral chemistry of juvenile blacktip sharks Carcharhinus limbatus was
      examined to identify whether differences existed among different regions of the
      vertebral column, between thoracic vertebrae of individual fish or within
      individual vertebrae. Additionally, the effects of bleach exposure and storage in
      ethanol on vertebral chemistry were compared. No significant variation in
      vertebral chemistry was found among different regions of the vertebral column or
      between thoracic vertebrae, but significant differences among transect locations
      within individual vertebrae were observed. The variation at all three levels
      appears comparable with published data on sagittal otoliths of bilaterally
      symmetrical teleost fishes. The experimental assessment of potential treatment
      effects indicated vertebral chemistry was not significantly affected by bleach or
      exposure to ethanol. Taken together, these results support the idea that
      vertebrae taken from the same region of the vertebral column can be treated as
      equivalent and at least certain elements remain robust to exposure to bleach and
      ethanol.

PMID- 29023720
TI  - A field test of the use of pop-off data storage tags in freshwater fishes.
AB  - In the present study, pop-off data storage tags (pDST) without any transmitting
      capabilities were attached to 118 adult salmonids in a 19 000 km2 freshwater
      system (Lake Ontario). The 9.3 cm long cylindrical tags were externally attached
      to fishes using a backpack-style harness, set to record pressure (dBar ~ depth in
      m) and temperature every 70 s (and at some key times, every 5 s) and programmed
      to release from the harness and float to the surface after c. 1 year. Recapture
      of the bright-orange tags for data retrieval relied on members of the public
      finding tags on shore, or on anglers capturing fishes with tags attached and
      using the contact information displayed on each tag to mail tags to the research
      team in exchange for a monetary reward. Thirty-seven tags were found and returned
      from the 118 released (31%), while 26 of the 118 tags (22%) remained scheduled to
      pop-off in summer 2017. Of the 37 tags returned, 23 were from wild-caught fishes
      (out of 88 wild-caught and tagged fishes; 26%) and yielded useful data whereas 14
      were from hatchery-reared fishes that were opportunistically tagged and appear to
      have been unable to acclimate to life in the wild and died days to weeks after
      release. The field study described here thus demonstrated that pDSTs can be a
      viable option for collecting large amounts of high-resolution depth and
      temperature data for salmonids in freshwater systems. Technical challenges,
      limitations and unknowns related to the use of pDSTs with freshwater fishes are
      discussed. In addition, pDSTs are compared with alternate electronic tagging
      technologies and assessed for their potential as a more widespread tool in
      research on freshwater fishes.

PMID- 29023721
TI  - Plant Phenolics Extraction from Flos Chrysanthemi: Response Surface Methodology
      Based Optimization and the Correlation Between Extracts and Free Radical
      Scavenging Activity.
AB  - : Huaiju is one of the most famous and widely used Flos Chrysanthemi (FC) for
      medicinal purposes in China. Although various investigations aimed at phenolics
      extraction from other FC have been reported, a thorough optimization of the
      phenolics extraction conditions from Huaiju has not been achieved. This work
      applied the widely used response surface methodology (RSM) to investigate the
      effects of 3 independent variables including ethanol concentration (%),
      extraction time (min), and solvent-to-material ratio (mL/g) on the ultrasound
      assisted extraction (UAE) of phenolics from FC. The data suggested the optimal
      UAE condition was an ethanol concentration of 75.3% and extraction time of 43.5
      min, whereas the ratio of solvent to material has no significant effect. When the
      free radical scavenging ability was used as an indicator for a successful
      extraction, a similar optimal extraction was achieved with an ethanol
      concentration of 72.8%, extraction time of 44.3 min, and the ratio of solvent to
      material was 29.5 mL/g. Furthermore, a moderate correlation between the
      antioxidant activity of TP extract and the content of extracted phenolic
      compounds was observed. Moreover, a well consistent of the experimental values
      under optimal conditions with those predicted values suggests RSM successfully
      optimized the UAE conditions for phenolics extraction from FC. PRACTICAL
      APPLICATION: The work of the research investigated the plant phenolics in Flos
      Chrysanthemi and antioxidant capacities. These results of this study can support
      the development of antioxidant additive and relative food.

PMID- 29023723
TI  - Total Ion Spectra versus Segmented Total Ion Spectra as Preprocessing Tools for
      Gas Chromatography - Mass Spectrometry Data.
AB  - Alignment of fire debris data from GC-MS for chemometric analysis is challenged
      by highly variable, uncontrolled sample and matrix composition. The total ion
      spectrum (TIS) obviates the need for alignment but loses all separation
      information. We introduce the segmented total ion spectrum (STIS), which retains
      the advantages of TIS while retaining some retention information. We compare the
      performance of STIS with TIS for the classification of casework fire debris
      samples. TIS and STIS achieve good model prediction accuracies of 96% and 98%,
      respectively. Baseline removal improved model prediction accuracies for both TIS
      and STIS to 97% and 99%, respectively. The importance of maintaining some
      chromatographic information to aid in deciphering the underlying chemistry of the
      results and reasons for false positive/negative results was also examined.

PMID- 29023722
TI  - Prevalence and clonality of synchronous primary carcinomas in the bladder and
      prostate.
AB  - Incidental prostate adenocarcinoma (IPCa) has been frequently discovered during
      postoperative histopathological evaluation of radical cystoprostatectomy
      specimens in patients with bladder cancer (BCa). However, there is currently no
      conclusive study addressing the clinical significance of IPCa and the clonal
      relatedness of IPCa and BCa. Here, we performed a retrospective single-center
      review of 919 BCa cases and an additional meta-analysis including a total of 19
      868 individuals who underwent radical cystectomy for bladder cancer. IPCa, mostly
      clinically insignificant, was detected in 67 of 919 BCa patients (7.3%) and was
      significantly associated with greater age. In the meta-analysis, a lower
      prevalence was observed in Asian than in non-Asian countries (19% versus 32%),
      presumably due to their different rates of prostate cancer occurrence. Whole
      exome sequencing on matched BCa and IPCa samples unambiguously revealed
      independent clonal origins of the synchronous tumors. BCa and IPCa lesions from
      each patient displayed distinctive genomic abnormalities and largely unrelated
      mutational signatures of single nucleotide variations, indicating disparate
      mutational processes underlying bladder and prostate oncogenesis. These findings
      provide important insights into the incidental nature of prostate adenocarcinoma
      in patients with bladder cancer, and suggest that the two concurrent diseases can
      be managed separately. Copyright (c) 2017 Pathological Society of Great Britain
      and Ireland. Published by John Wiley & Sons, Ltd.

PMID- 29023724
TI  - Immunity meets metabolism and then they start talking.

PMID- 29023729
TI  - Rebuttal from Ashley L. Bennett and Ian Scott Ramsey.

PMID- 29023728
TI  - Application of 3D Mass Spectrometry Imaging to TKIs.
AB  - Mass spectrometry imaging (MSI) allows visualization of endogenous and exogenous
      compound in tissue sections based on its molecular mass. The 3D reconstruction by
      MSI provides a more informative description of the tumor drug distribution
      compared to the high-performance liquid chromatography method, highlighting the
      heterogeneity of intratumor drug concentration. This additional information can
      be important in understanding chemoresistance to target agents. Here, we present
      the 3D visualization of the tyrosine kinase inhibitor (TKI), imatinib, in a
      xenograft model of resistant malignant pleural mesothelioma.

PMID- 29023730
TI  - CrossTalk opposing view: proton transfer in Hv1 utilizes a water wire, and does
      not require transient protonation of a conserved aspartate in the S1
      transmembrane helix.

PMID- 29023707
TI  - Guidelines for the use of flow cytometry and cell sorting in immunological
      studies.

PMID- 29023732
TI  - Murmur intensity in adult dogs with pulmonic and subaortic stenosis reflects
      disease severity.
AB  - OBJECTIVES: The aims of this study were to determine whether murmur intensity in
      adult dogs with pulmonic stenosis or subaortic stenosis reflects
      echocardiographic disease severity and to determine whether a six-level murmur
      grading scheme provides clinical advantages over a four-level scheme. MATERIALS
      AND METHODS: In this retrospective multi-investigator study on adult dogs with
      pulmonic stenosis or subaortic stenosis, murmur intensity was compared to
      echocardiographically determined pressure gradient across the affected valve.
      Disease severity, based on pressure gradients, was assessed between sequential
      murmur grades to identify redundancy in classification. A simplified four-level
      murmur intensity classification scheme ('soft', 'moderate', 'loud', 'palpable')
      was evaluated. RESULTS: In total, 284 dogs (153 with pulmonic stenosis, 131 with
      subaortic stenosis) were included; 55 dogs had soft, 59 had moderate, 72 had loud
      and 98 had palpable murmurs. 95 dogs had mild stenosis, 46 had moderate stenosis,
      and 143 had severe stenosis. No dogs with soft murmurs of either pulmonic or
      subaortic stenosis had transvalvular pressure gradients greater than 50 mmHg.
      Dogs with loud or palpable murmurs mostly, but not always, had severe stenosis.
      Stenosis severity increased with increasing murmur intensity. The traditional six
      level murmur grading scheme provided no additional clinical information than the
      four-level descriptive murmur grading scheme. CLINICAL SIGNIFICANCE: A simplified
      descriptive four-level murmur grading scheme differentiated stenosis severity
      without loss of clinical information, compared to the traditional six-level
      scheme. Soft murmurs in dogs with pulmonic or subaortic stenosis are strongly
      indicative of mild lesions. Loud or palpable murmurs are strongly suggestive of
      severe stenosis.

PMID- 29023731
TI  - Physiological tremor increases when skeletal muscle is shortened: implications
      for fusimotor control.
AB  - KEY POINTS: In tonic, isometric, plantarflexion contractions, physiological
      tremor increases as the ankle joint becomes plantarflexed. Modulation of
      physiological tremor as a function of muscle stretch differs from that of the
      stretch reflex amplitude. Amplitude of physiological tremor may be altered as a
      function of reflex pathway gains. Healthy humans likely increase their gamma
      static fusimotor drive when muscles shorten. Quantification of physiological
      tremor by manipulation of joint angle may be a useful experimental probe of
      afferent gains and/or the integrity of automatic fusimotor control. ABSTRACT: The
      involuntary force fluctuations associated with physiological (as distinct from
      pathological) tremor are an unavoidable component of human motor control. While
      the origins of physiological tremor are known to depend on muscle afferentation,
      it is possible that the mechanical properties of muscle-tendon systems also
      affect its generation, amplification and maintenance. In this paper, we
      investigated the dependence of physiological tremor on muscle length in healthy
      individuals. We measured physiological tremor during tonic, isometric
      plantarflexion torque at 30% of maximum at three ankle angles. The amplitude of
      physiological tremor increased as calf muscles shortened in contrast to the
      stretch reflex whose amplitude decreases as muscle shortens. We used a published
      closed-loop simulation model of afferented muscle to explore the mechanisms
      responsible for this behaviour. We demonstrate that changing muscle lengths does
      not suffice to explain our experimental findings. Rather, the model consistently
      required the modulation of  gamma-static fusimotor drive to produce increases in
      physiological tremor with muscle shortening - while successfully replicating the
      concomitant reduction in stretch reflex amplitude. This need to control gamma
      static fusimotor drive explicitly as a function of muscle length has important
      implications. First, it permits the amplitudes of physiological tremor and
      stretch reflex to be decoupled. Second, it postulates neuromechanical
      interactions that require length-dependent gamma drive modulation to be
      independent from alpha drive to the parent muscle. Lastly, it suggests that
      physiological tremor can be used as a simple, non-invasive measure of the
      afferent mechanisms underlying healthy motor function, and their disruption in
      neurological conditions.

PMID- 29023734
TI  - The life story from age 26 to 32: Rank-order stability and mean-level change.
AB  - OBJECTIVE: In this longitudinal, mixed-methods project, the primary focus was to
      examine the rank-order stability and mean-level change in the life story during
      the period of emerging adulthood to young adulthood, while also investigating how
      the transition to parenthood may impact the life story. METHOD: Seventy-two
      participants described three key life story scenes at age 26 and again at 32 (28%
      attrition from age 26 to 32). The narratives were coded for a range of features,
      including motivational themes (agency, communion), affective themes (emotional
      tone), an integrative meaning theme (coherent positive resolution), and a
      structural property (narrative complexity). RESULTS: Overall, there was moderate
      temporal stability and mean-level increase in several features of narrative
      identity over this key period. Positive changes in communion levels and overall
      emotional tone of life story scenes were especially evident for new parents at
      age 32. CONCLUSIONS: These longitudinal results suggested that adopting new
      social roles, in this case becoming a parent, predicted how the life story was
      expressed, just as they seemed to influence other levels of personality, such as
      traits, following the social investment principle.

PMID- 29023735
TI  - Shortening of an existing generic online health-related quality of life
      instrument for dogs.
AB  - OBJECTIVE: Development, initial validation and reliability testing of a shortened
      version of a web-based questionnaire instrument to measure generic health-related
      quality of life in companion dogs, to facilitate smartphone and online use.
      MATERIALS AND METHODS: The original 46 items were reduced using expert judgment
      and factor analysis. Items were removed on the basis of item loadings and
      communalities on factors identified through factor analysis of responses from
      owners of healthy and unwell dogs, intrafactor item correlations, readability of
      items in the UK, USA and Australia and ability of individual items to
      discriminate between healthy and unwell dogs. Validity was assessed through
      factor analysis and a field trial using a "known groups" approach. Test-retest
      reliability was assessed using intraclass correlation coefficients. RESULTS: The
      new instrument comprises 22 items, each of which was rated by dog owners using a
      7-point Likert scale. Factor analysis revealed a structure with four health
      related quality of life domains (energetic/enthusiastic, happy/content,
      active/comfortable, and calm/relaxed) accounting for 72% of the variability in
      the data compared with 64% for the original instrument. The field test involving
      153 healthy and unwell dogs demonstrated good discriminative properties and high
      intraclass correlation coefficients. CLINICAL SIGNIFICANCE: The 22-item shortened
      form is superior to the original instrument and can be accessed via a mobile
      phone app. This is likely to increase the acceptability to dog owners as a
      routine wellness measure in health care packages and as a therapeutic monitoring
      tool.

PMID- 29023733
TI  - Tonic inhibition of brown adipose tissue sympathetic nerve activity via
      muscarinic acetylcholine receptors in the rostral raphe pallidus.
AB  - KEY POINTS: A tonically active, muscarinic cholinergic inhibition of rostral
      raphe pallidus (rRPa) neurons influences thermogenesis of brown adipose tissue
      (BAT) independent of ambient temperature conditions. The tonically active
      cholinergic input to rRPa originates caudal to the hypothalamus. Muscarinic
      acetylcholine receptor (mAChR) activation in rRPa contributes to the inhibition
      of BAT sympathetic nerve activity (SNA) evoked by activation of neurons in the
      rostral ventrolateral medulla (RVLM). The RVLM is not the sole source of the
      muscarinic cholinergic input to rRPa. Activation of GABA receptors in rRPa does
      not mediate the cholinergic inhibition of BAT SNA. ABSTRACT: We sought to
      determine if body temperature and energy expenditure are influenced by a
      cholinergic input to neurons in the rostral raphe pallidus (rRPa), the site of
      sympathetic premotor neurons controlling thermogenesis of brown adipose tissue
      (BAT). Nanoinjections of the muscarinic acetylcholine receptor (mAChR) agonist,
      oxotremorine, or the cholinesterase inhibitor, neostigmine (NEOS), in the rRPa of
      anaesthetized rats decreased cold-evoked BAT sympathetic nerve activity (SNA,
      nadirs: -72 and -95%), BAT temperature (Tbat, -0.5 and -0.6 degrees C), expired
      CO2 (Exp. CO2 , -0.3 and -0.5%) and heart rate (HR, -22 and -41 bpm). NEOS into
      rRPa reversed the increase in BAT SNA evoked by blockade of GABA receptors in
      rRPa. Nanoinjections of the mAChR antagonist, scopolamine (SCOP), in the rRPa of
      warm rats increased BAT SNA (peak: +1087%), Tbat (+1.8 degrees C), Exp. CO2
      (+0.7%), core temperature (Tcore, +0.5 degrees C) and HR (+54 bpm). SCOP
      nanoinjections in rRPa produced similar activations of BAT during cold exposure,
      following a brain transection caudal to the hypothalamus, and during the blockade
      of glutamate receptors in rRPa. We conclude that a tonically active cholinergic
      input to the rRPa inhibits BAT SNA via activation of local mAChR. The inhibition
      of BAT SNA mediated by mAChR in rRPa does not depend on activation of GABA
      receptors in rRPa. The increase in BAT SNA following mAChR blockade in rRPa does
      not depend on the activity of neurons in the hypothalamus or on glutamate
      receptor activation in rRPa.

PMID- 29023736
TI  - An investigation of fetal behavioural states during maternal sleep in healthy
      late gestation pregnancy: an observational study.
AB  - KEY POINTS: Fetal behavioural state in healthy late gestation pregnancy is
      significantly affected by maternal position overnight. Maternal left lateral
      position is the one most frequently adopted at sleep onset. The maternal position
      at sleep onset is maintained the longest overnight. Fetal state 1F is more common
      in maternal supine positions overnight. Fetal state 4F is less common in maternal
      supine sleep positions. Fetal state and maternal sleep position are independently
      associated with fetal heart rate variability. Maternal sleep position
      significantly affects fetal heart rate and heart rate variability and affects
      circadian fetal heart rate patterns. ABSTRACT: Fetal behavioural states (FBS) are
      measures of fetal wellbeing. Maternal position affects FBS with supine position
      being associated with an increased likelihood of fetal quiescence consistent with
      the human fetus adapting to a lower oxygen consuming state. Several studies have
      now confirmed the association between sleep position and risk of late
      intrauterine death. We designed this study to observe the effects of maternal
      sleep positions overnight in healthy late gestation pregnancy. Twenty-nine
      healthy women had continuous fetal ECG recordings overnight. Two blinded
      observers assigned fetal states in 5 min blocks. Measures of fetal heart rate
      variability (FHRV) were calculated from ECG beat to beat data. Maternal position
      was determined from infrared video recording. Compared to state 2F (active
      sleep), 4F (active awake-high activity) occurred almost exclusively when the
      mother was in a left or right lateral position. State 1F (quiet sleep) was more
      common when the mother was supine [odds ratio (OR) 1.30, 95% confidence interval
      (CI) 1.11-1.52] and less common on the maternal right side with the left being
      the referent position (OR 0.81, 95% CI, 0.70-0.93). State 4F was more common
      between 21.00 and 01.00 h than between 01.00 and 07.00 h (OR 2.83, 95% CI 2.32
      3.47). In each fetal state, maternal position had significant effects on fetal
      heart rate and measures of FHRV. In healthy late gestation pregnancy, maternal
      sleep position affects FBS and heart rate variability. These effects are probably
      fetal adaptations to positions which may produce a mild hypoxic stress.

PMID- 29023739
TI  - Serum cardiac troponin I concentrations in dogs with generalised seizures.
AB  - OBJECTIVES: To determine if serum cardiac troponin I concentrations - measured
      with both a first-generation assay and a high-sensitivity assay - were greater in
      dogs with generalised seizures than in controls and to identify clinical
      variables associated with cardiac troponin I concentration. MATERIALS AND
      METHODS: Prospective study of 30 dogs with recent generalised seizures and 30
      healthy controls. Serum cardiac troponin I concentration was measured using two
      commercially available assays, and the correlation of clinical factors with
      concentration was examined. RESULTS: Serum concentrations of cardiac troponin I
      were higher in dogs that had recent seizures compared to controls when measured
      by both assays. The predictors most clearly associated with cardiac troponin I
      concentration were number of seizures and age. Both predictors were positively
      associated with increasing concentrations of troponin I. CLINICAL SIGNIFICANCE:
      Serum cardiac troponin I concentration was significantly elevated in dogs that
      had recent generalised seizures when compared to controls, and concentrations
      were higher in dogs that experienced more seizures. This association may indicate
      that generalised seizures are associated with damage to the myocardium.

PMID- 29023737
TI  - Oxidative phosphorylation: regulation and role in cellular and tissue metabolism.
AB  - Oxidative phosphorylation provides most of the ATP that higher animals and plants
      use to support life and is responsible for setting and maintaining metabolic
      homeostasis. The pathway incorporates three consecutive near equilibrium steps
      for moving reducing equivalents between the intramitochondrial [NAD+ ]/[NADH]
      pool to molecular oxygen, with irreversible reduction of oxygen to bound peroxide
      at cytochrome c oxidase determining the net flux. Net flux (oxygen consumption
      rate) is determined by demand for ATP, with feedback by the energy state
      ([ATP]/[ADP][Pi ]) regulating the pathway. This feedback affects the reversible
      steps equally and independently, resulting in the rate being coupled to
      ([ATP]/[ADP][Pi ])3 . With increasing energy state, oxygen consumption decreases
      rapidly until a threshold is reached, above which there is little further
      decrease. In most cells, [ATP] and [Pi ] are much higher than [ADP] and change in
      [ADP] is primarily responsible for the change in energy state. As a result, the
      rate of ATP synthesis, plotted against [ADP], remains low until [ADP] reaches
      about 30 MUm and then increases rapidly with further increase in [ADP]. The
      dependencies on energy state and [ADP] near the threshold can be fitted by the
      Hill equation with a Hill coefficients of about -2.6 and 4.2, respectively. The
      homeostatic set point for metabolism is determined by the threshold, which can be
      modulated by the PO2 and intramitochondrial [NAD+ ]/[NADH]. The ability of
      oxidative phosphorylation to precisely set and maintain metabolic homeostasis is
      consistent with it being permissive of, and essential to, development of higher
      plants and animals.

PMID- 29023738
TI  - KLF2 mediates enhanced chemoreflex sensitivity, disordered breathing and
      autonomic dysregulation in heart failure.
AB  - KEY POINTS: Enhanced carotid body chemoreflex activity contributes to development
      of disordered breathing patterns, autonomic dysregulation and increases in
      incidence of arrhythmia in animal models of reduced ejection fraction heart
      failure. Chronic reductions in carotid artery blood flow are associated with
      increased carotid body chemoreceptor activity. Kruppel-like Factor 2 (KLF2) is a
      shear stress-sensitive transcription factor that regulates the expression of
      enzymes which have previously been shown to play a role in increased chemoreflex
      sensitivity. We investigated the impact of restoring carotid body KLF2 expression
      on chemoreflex control of ventilation, sympathetic nerve activity, cardiac
      sympatho-vagal balance and arrhythmia incidence in an animal model of heart
      failure. The results indicate that restoring carotid body KLF2 in chronic heart
      failure reduces sympathetic nerve activity and arrhythmia incidence, and improves
      cardiac sympatho-vagal balance and breathing stability. Therapeutic approaches
      that increase KLF2 in the carotid bodies may be efficacious in the treatment of
      respiratory and autonomic dysfunction in heart failure. ABSTRACT: Oscillatory
      breathing and increased sympathetic nerve activity (SNA) are associated with
      increased arrhythmia incidence and contribute to mortality in chronic heart
      failure (CHF). Increased carotid body chemoreflex (CBC) sensitivity plays a role
      in this process and can be precipitated by chronic blood flow reduction. We
      hypothesized that downregulation of a shear stress-sensitive transcription
      factor, Kruppel-like Factor 2 (KLF2), mediates increased CBC sensitivity in CHF
      and contributes to associated autonomic, respiratory and cardiac sequelae.
      Ventilation (Ve), renal SNA (RSNA) and ECG were measured at rest and during CBC
      activation in sham and CHF rabbits. Oscillatory breathing was quantified as the
      apnoea-hypopnoea index (AHI) and respiratory rate variability index (RRVI). AHI
      (control 6 +/- 1/h, CHF 25 +/- 1/h), RRVI (control 9 +/- 3/h, CHF 29 +/- 3/h),
      RSNA (control 22 +/- 2% max, CHF 43 +/- 5% max) and arrhythmia incidence (control
      50 +/- 10/h, CHF 300 +/- 100/h) were increased in CHF at rest ( 

PMID- 29023740
TI  - Surveillance and monitoring of oral health in elderly people.
AB  - Continued ageing of the global population is expected to pose significant
      challenges to maintaining optimum lifelong health in individuals and populations.
      Oral health is an essential element of general health and quality of life
      throughout an individual's life course, yet it is often neglected in integrated
      approaches to general health promotion. Surveillance and monitoring systems are
      essential for developing oral health policy and strategy at both national and
      community levels. As major oral diseases, dental caries and periodontal diseases
      are core indicators for surveillance at every stage of life. In addition, oral
      mucosal lesions and masticatory function are essential indicators, especially in
      an ageing population. The assessment of risk factors such as tobacco use, alcohol
      consumption or dietary habits (e.g., sugar intake) is also important for oral
      disease prevention. Although surveillance is conducted through clinical
      examinations (normative assessments), this method is becoming more difficult to
      use because of high costs and human resource shortages, even in high-income
      countries. Alternative and less resource-demanding approaches, such as self
      reported protocols, are therefore needed at the global level. The World Health
      Organization's (WHO) oral health surveillance and monitoring activities have
      evolved into the Oral Health STEPwise approach, which includes questionnaire
      surveys (Step 1) and clinical examinations (Step 2). Collaboration between
      international organisations such as the World Dental Federation (FDI), WHO and
      the International Association for Dental Research (IADR) is now needed to
      coordinate global oral health surveillance and monitoring systems.

PMID- 29023741
TI  - Oral healthcare systems for an ageing population: concepts and challenges.
AB  - Oral healthcare systems (OHCS) are designed to maintain the health and function
      through Communication (Health promotion and education), Prevention, Assessment
      and Diagnosis, and Treatment. The complexity of these OHCS functions for the
      ageing are described utilizing the spectrum of dependency of the Seattle Care
      Pathway framework. Barriers and disparities which challenge the development of
      OHCS for the ageing can be universal but often vary between developed and
      developing countries. Recognizing that oral diseases are largely preventable,
      strategies to improve OHCS must be targeted locally, nationally, and
      internationally at oral health policy, education, research, and clinical care.

PMID- 29023742
TI  - Oral health for healthy longevity in an ageing society: maintaining momentum and
      moving forward.
AB  - The ageing of populations worldwide is rapidly accelerating. However, the global
      burden of oral disease remains a critical and often underestimated problem. As
      ageing progresses globally, oral health maintenance becomes a matter not only of
      public health, but also of human rights. Therefore, in low- and middle-income
      countries, policymakers are seeking to realize universal health coverage even as
      they struggle with severe resource limitations. To achieve and maintain global
      oral health, we propose an ongoing global monitoring cycle consisting of the
      following four steps: needs assessment, implementation of appropriate health care
      systems and provisions, reducing the global burden of oral disease, and working
      to achieve a healthy ageing society. Rather than a unidirectional information
      flow from high income to low- and middle-income countries, the proposed system
      would establish a multidirectional information-sharing cycle that would benefit
      all countries. To make this possible, however, we must develop a standardized set
      of core oral health indicators that all countries use, as well as a global
      repository for gathering, compiling, and sharing the data. This system would
      allow each country to move forward at its own pace and in locally-appropriate
      ways, making it more effective and efficient in the long run than the current
      pattern of setting unrealistic goals that all countries are expected to achieve
      by a certain point in time.

PMID- 29023743
TI  - Oral health for an ageing population: the importance of a natural dentition in
      older adults.
AB  - Despite progress in dentistry, tooth loss in old age is still a reality, even
      more so in long-term-care residents. However, recent trends indicate that natural
      teeth are lost later in life. Functional decline and age-related pathologies have
      to be considered in oral health care for this vulnerable population. Retaining
      and restoring teeth and oral function in elders is important. Tooth loss
      significantly impairs masticatory performance, which cannot be fully restored by
      prosthodontic means. Hence an unconscious change in food intake occurs, often
      involving malnutrition and withdrawal from common meals. Poor oral appearance and
      bad breath may further impede social activities. Although a chewing activity may
      be beneficial for cognitive function, natural teeth can present a considerable
      risk for fragile elders, in whom aspiration of biofilm can lead to pneumonia and
      death. The presence of natural teeth is also correlated with higher life
      expectancy, but socio-economic confounding factors have to be considered. When
      evaluating oral health in the elderly population, standards and priorities for
      reporting oral health outcome measures have to be defined. Anatomical indicators
      such as the number of natural teeth or the presence of prostheses might be one
      option for reporting. However, functional indicators such as masticatory
      performance and patient-centred outcome measures may be more relevant. In
      conclusion, there is an overwhelming body of evidence that maintaining a healthy
      natural dentition in old age is beneficial from a structural, functional and
      psycho-social point of view.

PMID- 29023744
TI  - The relationship of oral health with general health and NCDs: a brief review.
AB  - Oral health is closely related to systemic health. Periodontitis, a chronic
      inflammatory disease which is highly prevalent worldwide, interacts with a
      variety of noncommunicable diseases (NCDs). It is a risk factor in the complex
      pathogenesis of diabetes mellitus and cardiovascular disease and plays a role in
      the development of endocarditis and recurrent pneumonia in elderly people.
      However, the available data may be interpreted in different ways, and more and
      better-designed studies are still needed to answer relevant questions about the
      causal role of periodontitis in NCDs. What is clear is that periodontitis
      contributes to the systemic inflammatory burden. As periodontitis shares many
      common risk factors with NCDs, close collaboration between physicians and
      dentists is needed to increase the chance of early detection and improve the
      prevention and control of these conditions.

PMID- 29023745
TI  - Prevention of tooth loss and dental pain for reducing the global burden of oral
      diseases.
AB  - Population ageing is a global phenomenon and is predicted to become one of the
      most significant social transformations of the 21st century. The anticipated
      demographic shift provides governments the opportunity to proactively align
      policies with the estimated demands for housing, transportation, social
      protection, and health and well-being. Oral health is a fundamental component of
      health and physical and mental well-being, and is influenced by the individual's
      changing experience, perceptions, expectations and ability to adapt to
      circumstances. As such, prevention of oral disease and maintenance of oral health
      contributes to the systemic health, well-being, and quality of life of older
      adults. Dental caries, periodontal disease, and tooth loss in older adults are
      global health concerns because they are highly prevalent worldwide, socio
      economic inequalities contribute to these diseases, many of the risk factors are
      modifiable, and these diseases result in compromised oral health-related quality
      of life. Oral care must be tailored to the needs and level of dependency of older
      adults through the use of evidence-based approaches and inter-professional
      collaboration. The persistence of between countries and within countries oral
      health disparities indicate that population-based policies are also needed to
      address the underlying social, environmental, and economic causes of oral
      diseases.

PMID- 29023746
TI  - Corrigendum.

PMID- 29023747
TI  - Cross-sectional study of associations between prior spontaneous abortions and
      preterm delivery.
AB  - OBJECTIVE: To evaluate associations between a history of spontaneous abortion and
      preterm delivery during subsequent pregnancies. METHODS: The present secondary
      analysis included cross-sectional survey data related to all deliveries at 103
      hospitals in Tehran, Iran, between July 6 and 21, 2015. Trained midwives
      interviewed patients within 24 hours of delivery. Adjusted odds ratios (ORs) with
      95% confidence intervals (CIs) were calculated to investigate associations
      between spontaneous abortion and preterm delivery. RESULTS: Data were included
      from 4991 deliveries. A history of spontaneous abortion (OR 1.50, 95% CI 1.21
      1.87; P=0.001) and history of recurrent spontaneous abortion (OR 3.74, 95% CI
      1.90-7.37; P=0.001) were associated with increased odds of preterm delivery in
      comparison with no such history. Similarly, one (OR 1.33, 95% CI 1.04-1.70;
      P=0.023), two (OR 1.78, 95% CI 1.15-2.74; P=0.009), or at least three prior
      spontaneous abortions (OR 4.10, 95% CI 2.08-8.08; P=0.001) were associated with
      increased odds of preterm delivery compared with none. Population attributable
      fractions of 9.49% (95% CI 3.36-15.12) and 2.00% (95% CI 0.57-3.56) were
      calculated for histories of spontaneous abortion and recurrent pregnancy loss,
      respectively. CONCLUSION: History of spontaneous abortion and history of
      recurrent pregnancy loss were associated with increased odds of preterm delivery.
      A greater number of spontaneous abortions corresponded to greater odds of preterm
      delivery.

PMID- 29023748
TI  - What cervical screening is appropriate for women who have been vaccinated against
      high risk HPV? A simulation study.
AB  - Women vaccinated against HPV16/18 are approaching the age for cervical screening;
      however, an updated screening algorithm has not been agreed. We use a
      microsimulation model calibrated to real published data to determine the
      appropriate screening intensity for vaccinated women. Natural histories in the
      absence of vaccination were simulated for 300,000 women using 10,000 sets of
      transition probabilities. Vaccination with (i) 100% efficacy against HPV16/18,
      (ii) 15% cross-protection, (iii) 22% cross-protection, (iv) waning vaccine
      efficacy and (v) 100% efficacy against HPV16/18/31/33/45/52/58 was added, as were
      a range of screening scenarios appropriate to the UK. To benchmark cost-benefits
      of screening for vaccinated women, we evaluated the proportion of cancers
      prevented per additional screen (incremental benefit) of current cytology and
      likely HPV screening scenarios in unvaccinated women. Slightly more cancers are
      prevented through vaccination with no screening (70.3%, 95% CR: 65.1-75.5) than
      realistic compliance to the current UK screening programme in the absence of
      vaccination (64.3%, 95% CR: 61.3-66.8). In unvaccinated women, when switching to
      HPV primary testing, there is no loss in effectiveness when doubling the
      screening interval. Benchmarking supports screening scenarios with incremental
      benefits of >=2.0%, and rejects scenarios with incremental benefits <=0.9%. In
      HPV16/18-vaccinated women, the incremental benefit of offering a third lifetime
      screen was at most 3.3% (95% CR: 2.2-4.5), with an incremental benefit of 1.3% (
      0.3-2.8) for a fourth screen. For HPV16/18/31/33/45/52/58-vaccinated women, two
      lifetime screens are supported. It is important to know women's vaccination
      status; in these simulations, HPV16/18-vaccinated women require three lifetime
      screens, HPV16/18/31/33/45/52/58-vaccinated women require two lifetime screens,
      yet unvaccinated women require seven lifetime screens.

PMID- 29023749
TI  - Preparative isolation and purification of capsaicin and dihydrocapsaicin from
      Capsici Fructus using supercritical fluid extraction combined with high speed
      countercurrent chromatography.
AB  - BACKGROUND: Supercritical fluid extraction with CO2 (SFE-CO2 ) was utilized for
      extraction of capsaicin (CA) and dihydrocapsaicin (DHCA) from Capsici Fructus,
      and then a two-step enrichment method for separating capsaicinoids from SFE-CO2
      extracts was developed. The process involved extraction with aqueous methanol and
      crystallization by alkali extraction and acid precipitation. Finally, a
      consecutive high-speed countercurrent chromatography (HSCCC) separation method
      was successfully applied in the purification of CA and DHCA from capsaicinoid
      crystal. RESULTS: The extraction pressure, extraction temperature and volume of
      co-solvent were optimized at 33 MPa, 41  degrees C and 75 mL, respectively, using
      response surface methodology; the extraction rates of CA and DHCA were about
      93.18% and 93.49%, respectively. 407.43 mg capsaicinoid crystal was isolated from
      the SFE-CO2 extracts obtained from 100 g capsicum powder by the two-step
      enrichment method. About 506 mg and 184 mg CA and DHCA with purities up to 98.31%
      and 96.68%, respectively, were obtained from 1 g capsaicinoid crystal in one
      HSCCC of three consecutive sample loadings without exchanging any solvent system.
      CONCLUSIONS: This method comprising SFE-CO2 , a two-step enrichment and HSCCC was
      efficient, powerful and practical for the large-scale preparation of CA and DHCA
      from Capsici Fructus with high purity and high yield. (c) 2017 Society of
      Chemical Industry.

PMID- 29023750
TI  - Trends in antigen-negative red blood cell distributions by racial or ethnic
      groups in the United States.
AB  - BACKGROUND: The overall number of red blood cell (RBC) units distributed to
      hospitals throughout the world and in the United States has decreased lately.
      This study was performed to determine if the number of antigen-negative RBC units
      distributed to hospitals has followed this trend. STUDY DESIGN AND METHODS:
      Stratified by ethnicity, data on total RBC distributions and antigen-negative RBC
      distributions from six large blood collectors in the United States were obtained
      from 2009 through 2016. An antigen-negative unit was defined as a unit with a
      specific RBC phenotype that had been specially ordered as such by a hospital.
      RESULTS: Overall, 10,103,703 RBC units were distributed by these six blood
      collectors; 650,516 (6.4%) were distributed as antigen-negative units. While the
      overall number of RBCs distributed decreased by 27.2% between 2009 and 2016, the
      number of antigen-negative RBC distributions increased by 39.5%. In each year,
      the majority of the distributed antigen-negative RBCs were donated by whites.
      However, antigen-negative RBC units from black or African American donors were
      distributed in a disproportionately high fraction compared to the overall number
      of RBCs distributed from these donors. Most of the one through four antigen
      negative RBCs were donated by whites. However, as antigen matching became more
      extensive, the proportion of units distributed from black or African American
      donors increased such that they were the predominant donors of five or more
      antigen-negative units. CONCLUSION: Blood collectors will need to be aware of the
      trend of increasing antigen-negative distributions despite decreased overall
      distributions.

PMID- 29023751
TI  - The use of factorial design to evaluate the oxidation of oils containing
      different types of omega-3 fatty acids.
AB  - BACKGROUND: Omega-3 fatty acids (n3 FA) promote beneficial effects on
      cardiovascular diseases, but they are highly susceptible to oxidation, which
      leads to the formation of potentially toxic secondary products. In this study,
      the antioxidant capacity of natural compounds (sinapic acid and rutin) was
      evaluated using an accelerated model to oxidize the oils. Five inducers
      (temperature, Fe2+ , 2,2'-azobis(2-amidinopropane) dihydrochloride, ascorbyl
      palmitate and the hydrophobic 2,2'-azobis-2,4-dimethylvaleronitrile (AMVN)) were
      combined in a factorial design to accelerate the oxidation of three oils
      (flaxseed, echium and fish) containing different sources of n3 FA. RESULTS: Lipid
      hydroperoxide (LOOH) and thiobarbituric acid reactive substance (TBARS)
      concentrations estimated using the regression models did not differ from the
      observed values. AMVN + Fe2+ increased TBARS in all samples. CONCLUSION: The
      values for the oxidative markers obtained 48 h after induction were similar to
      those obtained when the oils were heated at 60  degrees  C for 15 days. Of a
      number of volatile compounds formed from the oxidation of different n3 FA
      sources, (E,E)-2,4-heptadienal, (E,E)-2,4-decadienal, decanal, undecanal and (E)
      2-undecenal were identified in all samples and could be used as more specific
      oxidative markers. Using the accelerated model, rutin improved the oxidative
      stability of fish oil, probably due to the presence of a catechol group in its
      chemical structure. (c) 2017 Society of Chemical Industry.

PMID- 29023752
TI  - A novel R3 MYB transcriptional repressor associated with the loss of floral
      pigmentation in Iochroma.
AB  - Losses of floral pigmentation represent one of the most common evolutionary
      transitions in flower color, yet the genetic basis for these changes has been
      elucidated in only a handful of cases. Here we used crossing studies, bulk
      segregant RNA sequencing, phylogenetic analyses and functional tests to identify
      the gene(s) responsible for the transition to white flowers in Iochroma loxense.
      Crosses between I. loxense and its blue-flowered sister species, I. cyaneum,
      suggested that a single locus controls the flower color difference and that the
      white allele causes a nearly complete loss of pigmentation. Examining sequence
      variation across phenotypic pools from the crosses, we found that alleles at a
      novel R3 MYB transcription factor were tightly associated with flower color
      variation. This gene, which we term MYBL1, falls into a class of MYB
      transcriptional repressors and, accordingly, higher expression of this gene is
      associated with downregulation of multiple anthocyanin pigment pathway genes. We
      confirmed the repressive function of MYBL1 through stable transformation of
      Nicotiana. The mechanism underlying the evolution of white flowers in I. loxense
      differs from that uncovered in previous studies, pointing to multiple mechanisms
      for achieving fixed transitions in flower color intensity.

PMID- 29023753
TI  - Postharvest monitoring of organic potato (cv. Anuschka) during hot-air drying
      using visible-NIR hyperspectral imaging.
AB  - BACKGROUND: The potential of hyperspectral imaging (500-1010 nm) was evaluated
      for monitoring of the quality of potato slices (var. Anuschka) of 5, 7 and 9 mm
      thickness subjected to air drying at 50  degrees C. The study investigated three
      different feature selection methods for the prediction of dry basis moisture
      content and colour of potato slices using partial least squares regression (PLS).
      RESULTS: The feature selection strategies tested include interval PLS regression
      (iPLS), and differences and ratios between raw reflectance values for each
      possible pair of wavelengths (R[lambda1 ]-R[lambda2 ] and R[lambda1 ]:R[lambda2
      ], respectively). Moreover, the combination of spectral and spatial domains was
      tested. Excellent results were obtained using the iPLS algorithm. However,
      features from both datasets of raw reflectance differences and ratios represent
      suitable alternatives for development of low-complex prediction models. Finally,
      the dry basis moisture content was high accurately predicted by combining
      spectral data (i.e. R[511 nm]-R[994 nm]) and spatial domain (i.e. relative area
      shrinkage of slice). CONCLUSIONS: Modelling the data acquired during drying
      through hyperspectral imaging can provide useful information concerning the
      chemical and physicochemical changes of the product. With all this information,
      the proposed approach lays the foundations for a more efficient smart dryer that
      can be designed and its process optimized for drying of potato slices. (c) 2017
      Society of Chemical Industry.

PMID- 29023754
TI  - Local context influences memory for emotional stimuli but not
      electrophysiological markers of emotion-dependent attention.
AB  - Emotional enhancement of free recall can be context dependent. It is readily
      observed when emotional and neutral scenes are encoded and recalled together in a
      "mixed" list, but diminishes when these scenes are encoded separately in "pure"
      lists. We examined the hypothesis that this effect is due to differences in
      allocation of attention to neutral stimuli according to whether they are
      presented in mixed or pure lists, especially when encoding is intentional. Using
      picture stimuli that were controlled for semantic relatedness, our results
      contradicted this hypothesis. The amplitude of well-known electrophysiological
      markers of emotion-related attention-the early posterior negativity (EPN), the
      late positive potential (LPP), and the slow wave (SW)-was higher for emotional
      stimuli. Crucially, the emotional modulation of these ERPs was insensitive to
      list context, observed equally in pure and mixed lists. Although list context did
      not modulate neural markers of emotion-related attention, list context did
      modulate the effect of emotion on free recall. The apparent decoupling of the
      emotional effects on attention and memory, challenges existing hypotheses
      accounting for the emotional enhancement of memory. We close by discussing
      whether findings are more compatible with an alternative hypothesis, where the
      magnitude of emotional memory enhancement is, at least in part, a consequence of
      retrieval dynamics.

PMID- 29023755
TI  - A Heartfelt Thanks to the Editors and Contributors of Special Issue 93:3.

PMID- 29023756
TI  - Working memory and attention are still impaired after three years in patients
      with stress-related exhaustion.
AB  - Cognitive impairment is one of the most pronounced symptoms reported by patients
      with stress-related mental health problems. Impairments related to executive
      function and to some extent speed and attention are therefore common in patients
      with stress-related burnout/exhaustion. In this paper we present a follow-up of
      cognitive performance in patients with stress-related exhaustion several years
      after they initially sought medical care. Thirty patients and 27 healthy
      controls, mean age 49 years (SD 6.5) and 55 years (SD 6.7) respectively, were
      included, all of whom had undergone baseline measurements of neuropsychological
      functioning. The mean follow-up time was three years. Half of the patients still
      reported mental health problems at follow-up and over time no major changes in
      cognitive performance were noted. The patients still performed significantly
      poorer than controls with regard to cognitive functions, mainly related to speed,
      attention and memory function. Long-lasting impairment of cognitive functions
      related to speed, attention and memory function noted in patients with stress
      related exhaustion should be acknowledged and taken into consideration during
      treatment and when discussing a return to work. Follow-up periods longer than
      three years are needed to explore the persistence of the cognitive impairment.

PMID- 29023757
TI  - Acute autoimmune hemolytic anemia due to anti-Ena autoantibody successfully
      treated with rituximab.
AB  - BACKGROUND: Autoimmune hemolytic anemia (AIHA) due to anti-Ena has been
      previously reported in association with massive intravascular hemolysis,
      disseminated intravascular coagulation, and fatal outcomes. Here we report a case
      of successfully treated AIHA due to anti-Ena . CASE REPORT: A 69-year-old male
      with a past medical history of cirrhosis due to nonalcoholic steatohepatitis
      status post-orthotopic liver transplant presented with 1-month history of
      progressive anemia. At presentation, his hemoglobin (Hb) was 5.6 g/dL, hematocrit
      (Hct) 16%, reticulocytes 0.3%, direct bilirubin (bili) 4 g/dL, lactate
      dehydrogenase 533 units/L (reference, 125-220 units/L), and haptoglobin 254 mg/dL
      (reference, 40-273 mg/dL). Blood bank testing revealed an autoantibody present in
      his plasma and a direct antiglobulin test positive for immunoglobulin G (IgC) but
      negative for complement. He received 1 unit of an incompatible blood group O
      phenotypically matched red blood cell unit. RESULTS: Over the course of the next
      5 days, the Hb and Hct decreased to 4.1 g/dL and 12%, respectively, direct bili
      increased to 12.3 mg/day, reticulocytes slightly increased to 0.9%, and
      haptoglobin decreased to less than 8 mg/dL. Marrow study showed a hypercellular
      marrow with erythroid hyperplasia. Additional workup performed at a reference
      laboratory identified an anti-Ena autoantibody. He received prednisone and weekly
      rituximab infusions and was monitored weekly. At the 2-month visit, Hb and Hct
      were 10 g/dL and 32%, respectively. CONCLUSION: Unlike two of the previously
      reported fatal cases of AIHA with anti-Ena specificity, this 69-year-old male
      treated with weekly rituximab infusion underwent clinical recovery and
      significant anemia improvement.

PMID- 29023758
TI  - Biological activities of Agave by-products and their possible applications in
      food and pharmaceuticals.
AB  - Agave leaves are considered a by-product of alcoholic beverage production
      (tequila, mezcal and bacanora) because they are discarded during the production
      process, despite accounting for approximately 50% of the total plant weight.
      These by-products constitute a potential source of Agave extracts rich in
      bioactive compounds, such as saponins, phenolic compounds and terpenes, and
      possess different biological effects, as demonstrated by in vitro and in vivo
      tests (e.g. antimicrobial, antifungal, antioxidant, anti-inflammatory,
      antihypertensive, immunomodulatory, antiparasitic and anticancer activity).
      Despite their positive results in biological assays, Agave extracts have not been
      widely evaluated in food systems and pharmaceutical areas, and these fields
      represent a potential route to improve the usage of Agave plants as food
      additives and agents for treating medical diseases. (c) 2017 Society of Chemical
      Industry.

PMID- 29023760
TI  - Listening to teachers: Views on delivery of a classroom based sensory
      intervention for students with autism.
AB  - BACKGROUND/AIM: Occupational therapists consider the impact of autism spectrum
      disorder on occupational performance at school. Occupational therapists work with
      teachers to support student participation. Atypical sensory processing is common
      in children with autism. Therefore, collaborating with teachers to enable
      students with autism to appropriately process sensory information within
      classrooms may be necessary. This qualitative pilot study aimed to capture
      teachers' perceptions of using a Sensory Activity Schedule, a sensory based
      intervention, in the classroom. METHODS: A qualitative descriptive approach was
      used to analyse semi-structured interview responses from 19 qualified teachers
      who taught children with autism from seven different autism specific special
      schools in NSW. Teachers were asked about their motivation to complete the
      intervention as well as helpful and difficult aspects of the intervention.
      FINDINGS: Three main categories and eight sub-categories were identified from the
      19 respondents who reported that helping their students was an important
      motivation for using a Sensory Activity Schedule as well as the opportunity to
      evaluate whether sensory based intervention was beneficial. Teachers reported
      that learning new ideas, working with an occupational therapist and seeing an
      increase in concentration and a reduction in undesired behaviours were positive
      aspects of utilising the intervention. Timing, staffing and fidelity of the
      intervention were areas of concern. CONCLUSION: Collaboration with classroom
      teachers is an essential part of school-based occupational therapy. Insights from
      teachers who implemented a sensory based intervention in the classroom assist
      occupational therapists to better support students with autism spectrum disorder
      in schools.

PMID- 29023759
TI  - Cord blood-derived T cells allow the generation of a more naive tumor-reactive
      cytotoxic T-cell phenotype.
AB  - BACKGROUND: Transplantation of hematopoietic stem cells (HSCs) from peripheral
      blood (PB) or cord blood (CB) is well established. HSCs from CB are associated
      with a lower risk of graft-versus-host disease (GVHD), but antigen-independent
      expanded CB- and PB-derived T cells can induce GVHD in allo-HSC recipients. CB
      derived cells might be more suitable for adoptive immunotherapy as they have
      unique T-cell characteristics. Here, we describe functional differences between
      CB and PB T cells stimulated with different cytokine combinations involved in
      central T-cell activation. STUDY DESIGN AND METHODS: Isolated CD8+ T cells from
      CB and PB were stimulated antigen independently with anti-CD3/CD28 stimulator
      beads or in an antigen-dependent manner with artificial antigen-presenting cells
      loaded with the HLA-A*02:01-restricted peptide of tumor-associated melanoma
      antigen recognized by T cells 1 (MART1). CB and PB T cells cultured in the
      presence of interleukin (IL)-7, IL-15, IL-12, and IL-21 were characterized for T
      cell phenotype and specificity, that is, by CD107a, interferon-gamma, tumor
      necrosis factor-alpha, and IL-2 expression. RESULTS: After antigen-independent
      stimulation, activated CD8+ CB T cells exhibited stronger proliferation and
      function than those from PB. After antigenic stimulation, MART1-reactive CB T
      cells were naive (CD45RA+CCR7+), cytotoxic, and highly variable in expressing
      homing marker CD62L. Addition of IL-21 resulted in increased T-cell
      proliferation, whereas supplementation with IL-12 decreased IL-21-induced
      expansion, but increased the functionality and cytotoxicity of CB and PB T cells.
      CONCLUSION: MART1-reactive CB T cells with a more naive phenotype and improved
      properties for homing can be generated. The results contribute to better
      understanding the effects on GVHD and graft versus tumor.

PMID- 29023761
TI  - Natural vitamin B12 and fucose supplementation of green smoothies with edible
      algae and related quality changes during their shelf life.
AB  - BACKGROUND: Some algae are an excellent sources of vitamin B12, of special
      interest for vegetarian/vegan consumers, and of fucose to supplement fruit and
      vegetable beverages such as smoothies. Nevertheless, supplementation of smoothies
      with algae may lead to possible quality changes during smoothie shelf life that
      need to be studied. Therefore, the quality changes in fresh green smoothies
      supplemented (2.2%) with nine edible algae (sea lettuce, kombu, wakame,
      thongweed, dulse, Irish moss, nori, Spirulina and Chlorella) were studied
      throughout 24 days at 5  degrees C. RESULTS: The initial vitamin C content -
      238.7-326.0 mg kg-1 fresh weight (FW) - of a 200 g portion of any of the
      smoothies ensured full coverage of its recommended daily intake, and still
      supplying 50-60% of the recommended intake after 7 days. Chlorella and Spirulina
      smoothies showed the highest vitamin B12 content (33.3 and 15.3 ug kg-1 FW,
      respectively), while brown algae showed fucose content of 141.1-571.3 mg kg-1 FW.
      These vitamin B12 and fucose contents were highly maintained during shelf life.
      CONCLUSION: The Spirulina supplementation of a 200 g smoothie portion ensured
      full coverage of the recommended vitamin B12 intake, with lower vitamin C
      degradation, during a shelf life of 17 days. Furthermore, thongweed and kombu are
      also considered as excellent fucose sources with similar shelf life. (c) 2017
      Society of Chemical Industry.

PMID- 29023762
TI  - Tolerance of olive (Olea europaea) cv Frantoio to Verticillium dahliae relies on
      both basal and pathogen-induced differential transcriptomic responses.
AB  - Verticillium wilt of olive (VWO) is one of the most serious biotic constraints
      for this tree crop. Our knowledge of the genetics of the tolerance/resistance to
      this disease is very limited. Here we show that tolerance of the cv Frantoio
      relies on both basal and early pathogen-induced differential transcriptomic
      responses. A comparative transcriptomic analysis (RNA-seq) was conducted in root
      tissues of cvs Frantoio (VWO-tolerant) and Picual (VWO-susceptible). RNA samples
      originated from roots of inoculated olive plants during the early infection
      stages by Verticillium dahliae (highly virulent, defoliating pathotype). A huge
      number of differentially expressed genes (DEGs) were found between 'Frantoio' and
      'Picual' (27 312 unigenes) in the absence of the pathogen. Upon infection with V.
      dahliae, 'Picual' and 'Frantoio' plants responded differently too. In the early
      infection stages, four clusters of DEGs could be identified according to their
      time-course expression patterns. Among others, a pathogenesis-related protein of
      the Bet v I family and a dirigent-like protein involved in lignification, and
      several BAK1, NHL1, reactive oxygen species stress response and BAM unigenes
      showed noticeable differences between cultivars. Tolerance of 'Frantoio' plants
      to VWO is a consequence of a complex and multifaceted process which involves many
      plant traits.

PMID- 29023763
TI  - CPS49-induced neurotoxicity does not cause limb patterning anomalies in
      developing chicken embryos.
AB  - Thalidomide notoriously caused severe birth defects, particularly to the limbs,
      in those exposed in utero following maternal use of the drug to treat morning
      sickness. How the drug caused these birth defects remains unclear. Many theories
      have been proposed including actions on the forming blood vessels. However,
      thalidomide survivors also have altered nerve patterns and the drug is known for
      its neurotoxic actions in adults following prolonged use. We have previously
      shown that CPS49, an anti-angiogenic analog of thalidomide, causes a range of
      limb malformations in a time-sensitive manner in chicken embryos. Here we
      investigated whether CPS49 also is neurotoxic and whether effects on nerve
      development impact upon limb development. We found that CPS49 is neurotoxic, just
      like thalidomide, and can cause some neuronal loss late developing chicken limbs,
      but only when the limb is already innervated. However, CPS49 exposure does not
      cause defects in limb size when added to late developing chicken limbs. In
      contrast, in early limb buds which are not innervated, CPS49 exposure affects
      limb area significantly. To investigate in more detail the role of neurotoxicity
      and its impact on chicken limb development we inhibited nerve innervation at a
      range of developmental timepoints through using beta-bungarotoxin. We found that
      neuronal inhibition or ablation before, during or after limb outgrowth and
      innervation does not result in obvious limb cartilage patterning or number
      changes. We conclude that while CPS49 is neurotoxic, given the late innervation
      of the developing limb, and that neuronal inhibition/ablation throughout limb
      development does not cause similar limb patterning anomalies to those seen in
      thalidomide survivors, nerve defects are not the primary underlying cause of the
      severe limb patterning defects induced by CPS49/thalidomide.

PMID- 29023764
TI  - Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS): A
      population-based cohort study of 32,839 one-year survivors.
AB  - Information on late onset liver complications after childhood cancer is scarce.
      To ensure an appropriate follow-up of childhood cancer survivors and reducing
      late liver complications, the need for comprehensive and accurate information is
      presented. We evaluate the risk of liver diseases in a large childhood cancer
      survivor cohort. We included all 1-year survivors of childhood cancer treated in
      the five Nordic countries. A Cox proportional hazards model was used to estimate
      hospitalisation rate (hazard) ratios (HRs) for each liver outcome according to
      type of cancer. We used the risk among survivors of central nervous system tumour
      as internal reference. With a median follow-up time of 10 years, 659 (2%)
      survivors had been hospitalised at least once for a liver disease. The risk for
      hospitalisation for any liver disease was high after hepatic tumour (HR = 6.9)
      and leukaemia (HR = 1.7). The Danish sub-cohort of leukaemia treated with
      haematopoietic stem cell transplantation had a substantially higher risk for
      hospitalisation for all liver diseases combined (HR = 3.8). Viral hepatitis
      accounted for 286 of 659 hospitalisations corresponding to 43% of all survivors
      hospitalised for liver disease. The 20-year cumulative risk of viral hepatitis
      was 1.8% for survivors diagnosed with cancer before 1990 but only 0.3% for those
      diagnosed after 1990. The risk of liver disease was low but significantly
      increased among survivors of hepatic tumours and leukaemia. Further studies with
      focus on the different treatment modalities are needed to further strengthen the
      prevention of treatment-induced late liver complications.

PMID- 29023765
TI  - Impact of clinicopathological characteristics on the efficacy of neoadjuvant
      therapy in patients with human epidermal growth factor receptor-2-positive breast
      cancer.
AB  - Neoadjuvant therapy has become increasingly common in human epidermal growth
      factor receptor-2 (HER2)-positive breast cancer. In this study, we examined the
      impact of different clinicopathological characteristics on pathological complete
      response (pCR) in patients treated with anti-HER2 agents. The PubMed and Embase
      databases were searched from inception through April 2017 to identify studies
      that met pre-specified criteria. The odds ratios (ORs) and 95% confidence
      intervals (CIs) were extracted directly or were calculated with other available
      information. Eleven randomized controlled trials (RCTs) that involved 3,269 HER2
      positive women were included in this meta-analysis. Patients with hormone
      receptor (HR)-negative breast cancer benefited more from anti-HER2 therapy than
      did patients with HR-positive tumours (OR, 2.25; 95% CI, 1.93-2.62). Furthermore,
      this improvement in pCR was independent of anti-HER2 agents, phase, combined
      chemotherapy, neoadjuvant duration, year the trials started and region where the
      trials were conducted. Patients with small tumours achieved greater benefits than
      patients with large tumours (OR, 1.25; 95% CI, 1.00-1.55). Age did not predict an
      additional benefit from anti-HER2 neoadjuvant treatment (OR, 1.02; 95% CI, 0.73
      1.45). The impact of nodal status on pCR was dependent on the anti-HER2 agents.
      In conclusion, for HER2-targeted neoadjuvant treatment in breast cancer, greater
      benefits were achieved in patients with small HR-negative tumours compared with
      patients with large HR-positive tumours. These results may improve drug
      development and treatment strategies, economic analyses and the design and
      interpretation of clinical trials.

PMID- 29023767
TI  - Do they stay or do they go? Acoustic monitoring of whale sharks at Ningaloo
      Marine Park, Western Australia.
AB  - Whale sharks Rhincodon typus were monitored via acoustic transmitters at the
      northern end of Western Australia's Ningaloo Marine Park to establish the extent
      to which the species inhabits the region beyond the whale-shark ecotourism
      industry season, which usually extends from March to August in each year. Despite
      the vast majority (c. 98%) of photographic submissions of R. typus from Ningaloo
      Reef being between March and August, acoustic detections from the tagged R. typus
      at Ningaloo were recorded in all months of the year, but do not preclude the
      occurrence of extended absences. It is concluded that as a species, R. typus
      occurs year round at Ningaloo, where it generally remains in close proximity to
      the reef edge, but that some individuals move outside of the detection range of
      the array for extended periods.

PMID- 29023766
TI  - Cannibalism in non-native brown trout Salmo trutta and rainbow trout Oncorhynchus
      mykiss stream-dwelling populations.
AB  - Introduced and allopatric populations of brown trout Salmo trutta and rainbow
      trout Oncorhynchus mykiss were sampled in Slovenia for stable isotope analysis to
      assess dietary niche shifts through ontogeny and estimate the propensity for
      cannibalism. Both S. trutta and O. mykiss are cannibals, with higher average
      relative contribution of conspecific assimilated energy for S. trutta (27.9%)
      compared with O. mykiss (7.7%). The smallest cannibal was 166 mm in the S. trutta
      population and 247 mm in the O. mykiss population.

PMID- 29023768
TI  - Changes in circulating inflammatory markers following febrile non-haemolytic
      transfusion reactions to leucoreduced red cells.
AB  - It would be desirable to be able to distinguish fever as a result of febrile non
      haemolytic transfusion reactions (FNHTR) from other febrile conditions. To
      further characterize the inflammatory feature of FNHTR, we measured a large panel
      of inflammatory markers in pre- and posttransfusion plasma samples from patients
      with and without FNHTR following the transfusion of leucoreduced red blood cells.
      As FNHTR patients only displayed a significant increase in IL-6, we conclude that
      changes in plasma cytokine levels during FNHTR are unlikely to be used
      diagnostically. An incidental finding of a distinct cytokine pattern in
      pretransfusion samples from FNHTR patients warrants further investigations, as it
      might be used to characterize the nature of FNHTR and to predict the risk of
      these adverse events.

PMID- 29023769
TI  - Alcohol consumption, variability in alcohol dehydrogenase genes and risk of renal
      cell carcinoma.
AB  - Alcohol consumption has been associated inversely with renal cell carcinoma (RCC)
      risk; however, no study has examined effect modification by germline variation in
      alcohol-metabolizing genes. We investigated whether the association between
      alcohol intake and RCC risk is modulated by germline variants in alcohol
      dehydrogenase genes in a large case-control study. Data from 652 RCC cases and
      1,366 non-cancer controls were analyzed. Alcohol intake was assessed using a
      standardized risk factor questionnaire. Three previously genotyped polymorphisms
      in ADH6 and ADH7 with the TaqMan assay were examined. Odds ratios (ORs) and 95%
      confidence interval (CI) were calculated using logistic regression, adjusting for
      covariates. Compared to non-drinkers, ever consumption of alcohol was associated
      with lower RCC risk (OR = 0.52, 95% CI = 0.42-0.65). Analysis with cubic spline
      regression curve showed a "J-shaped" relationship between alcohol drinks/day and
      RCC risk, such that there was no added benefit against RCC for consumption of
      more than two drinks/day. We observed effect modification by variation in
      rs1154454 (ADH7) (pinteraction  = 0.007); a per unit increase in alcohol
      drink/day was associated with 35% lower RCC risk among non-minor allele carriers,
      a 27% lower risk among those who carry one copy of the minor allele, but no
      association was observed among those with two copies of the minor allele. These
      findings indicate that alcohol consumption is associated with lower RCC risk.
      Consuming more than two drinks a day does not confer additional protection
      against RCC. The association between alcohol intake and RCC risk appears to be
      modulated by inter-individual germline variation in alcohol-metabolizing genes.

PMID- 29023770
TI  - C-C motif chemokine ligand 23 abolishes ER stress- and LPS-induced reduction in
      proliferation of bovine endometrial epithelial cells.
AB  - To reduce embryonic losses in domestic animals for economic production of
      livestock meat and milk, chemokines and their receptors are required for proper
      implantation and placentation during early pregnancy. In this study, we
      investigated the effects of C-C-motif chemokine ligand 23 (CCL23) on the
      proliferation of bovine endometrial (BEND) epithelial cells. CCL23 treatment
      improved BEND cell proliferation by enhancing PCNA and cyclin D1 expression via
      activation of the PI3K/AKT and MAPK signaling pathways. In addition, a
      combination of CCL23 and tunicamycin reversed the ER stress-induced reduction in
      cell proliferation and the decreased expression of UPR-mediated signaling
      proteins, including IRE1alpha, PERK, and ATF6alpha. Moreover, it regulated the
      lipopolysaccharide-induced inflammation in BEND cells by inhibiting the
      expression of pro-inflammatory cytokines (IL-6 and IL-8), and by restoring
      intracellular Ca2+ levels. These findings demonstrate that CCL23 improves
      endometrial development and uterine receptivity required for implantation and
      placentation during early pregnancy.

PMID- 29023771
TI  - Visibility of fiducial markers used for image-guided radiation therapy on optical
      coherence tomography for registration with CT: An esophageal phantom study.
AB  - PURPOSE: Optical coherence tomography (OCT) is of interest to visualize
      microscopic esophageal tumor extensions to improve tumor delineation for
      radiation therapy (RT) planning. Fiducial marker placement is a common method to
      ensure target localization during planning and treatment. Visualization of these
      fiducial markers on OCT permits integrating OCT and computed tomography (CT)
      images used for RT planning via image registration. We studied the visibility of
      13 (eight types) commercially available solid and liquid fiducial markers in OCT
      images at different depths using dedicated esophageal phantoms and evaluated
      marker placement depth in clinical practice. MATERIALS AND METHODS: We designed
      and fabricated dedicated esophageal phantoms, in which three layers mimic the
      anatomical wall structures of a healthy human esophagus. We successfully
      implanted 13 commercially available fiducial markers that varied in diameter and
      material property at depths between 0.5 and 3.0 mm. The resulting esophageal
      phantoms were imaged with OCT, and marker visibility was assessed qualitatively
      and quantitatively using the contrast-to-background-noise ratio (CNR). The CNR
      was defined as the difference between the mean intensity of the fiducial markers
      and the mean intensity of the background divided by the standard deviation of the
      background intensity. To determine whether, in current clinical practice, the
      implanted fiducial markers are within the OCT visualization range (up to 3.0 mm
      depth), we retrospectively measured the distance of 19 fiducial markers to the
      esophageal lumen on CT scans of 16 esophageal cancer patients. RESULTS: In the
      esophageal phantoms, all the included fiducial markers were visible on OCT at all
      investigated depths. Solid fiducial markers were better visible on OCT than
      liquid fiducial markers with a 1.74-fold higher CNR. Although fiducial marker
      identification per type and size was slightly easier for superficially implanted
      fiducial markers, we observed no difference in the ability of OCT to visualize
      the markers over the investigated depth range. Retrospective distance
      measurements of 19 fiducial markers on the CT scan of esophageal cancer patients
      showed that 84% (distance from the closest border of the marker to the lumen) and
      53% (distance from the center of the marker to the lumen) of the fiducial markers
      were located within the OCT visualization range of up to 3.0 mm. CONCLUSIONS: We
      studied the visibility of eight types of commercially available fiducial markers
      at different depths on OCT using dedicated esophageal phantoms. All tested
      fiducial markers were visible at depths <=3.0 mm and most, but not all,
      clinically implanted markers were at a depth accessible to OCT. Consequently, the
      use of fiducial markers as a reference for OCT to CT registration is feasible.

PMID- 29023773
TI  - Motive-goal congruence moderates the use of automatic self-regulation.
AB  - OBJECTIVE: We tested whether the fit between individuals' motives and goal
      properties predicts efficiency of implicit self-regulation. METHOD: Participants'
      (German university students; Mage  = 22; 64% female) implicit motives measurement
      (Multi-Motive Grid) was followed by assessment of implicit self-regulation in
      differently framed tasks. In Study 1 (N = 45), positive implicit evaluations of
      stimuli relating to an achievement goal (studying) were used as an indicator of
      implicit self-regulation. Study 2 (N = 70) framed a laboratory task as either
      achievement or power related, thus experimentally controlling the goal's
      properties, and assessed implicit evaluations for task-related stimuli with an
      evaluative priming paradigm. Study 3 (N = 67) contrasted playing a game framed as
      agency related (achievement, power) with a control condition. Implicit
      evaluations of task-related stimuli were assessed as an indicator of self
      regulation with an approach/avoidance task. RESULTS: In Study 1, implicit
      positive evaluations of an achievement goal were positively related to
      participants' achievement motive. Because of similarities between achievement and
      power, implicit positive evaluations of task-related stimuli were positively
      related to the achievement motive in both conditions of Study 2. In Study 3,
      positive implicit evaluations of the task were positively related to the agency
      motives only in the agency condition. CONCLUSIONS: Congruence between
      individuals' implicit motives and goal properties boosts implicit self
      regulation, thus identifying a promising predictor for success and failure in
      self-regulation that potentially mediates effects of goal-motive fit on goal
      pursuit.

PMID- 29023772
TI  - Negative modulation of the GABAA rho1 receptor function by l-cysteine.
AB  - l-Cysteine is an endogenous sulfur-containing amino acid with multiple and varied
      roles in the central nervous system, including neuroprotection and the
      maintenance of the redox balance. However, it was also suggested as an
      excitotoxic agent implicated in the pathogenesis of neurological disorders such
      as Parkinson's and Alzheimer's disease. l-Cysteine can modulate the activity of
      ionic channels, including voltage-gated calcium channels and glutamatergic NMDA
      receptors, whereas its effects on GABAergic neurotransmission had not been
      studied before. In the present work, we analyzed the effects of l-cysteine on
      responses mediated by homomeric GABAA rho1 receptors, which are known for
      mediating tonic gamma-aminobutyric acid (GABA) responses in retinal neurons.
      GABAA rho1 receptors were expressed in Xenopus laevis oocytes and GABA-evoked
      chloride currents recorded by two-electrode voltage-clamp in the presence or
      absence of l-cysteine. l-Cysteine antagonized GABAA rho1 receptor-mediated
      responses; inhibition was dose-dependent, reversible, voltage independent, and
      susceptible to GABA concentration. Concentration-response curves for GABA were
      shifted to the right in the presence of l-cysteine without a substantial change
      in the maximal response. l-Cysteine inhibition was insensitive to chemical
      protection of the sulfhydryl groups of the rho1 subunits by the irreversible
      alkylating agent N-ethyl maleimide. Our results suggest that redox modulation is
      not involved during l-cysteine actions and that l-cysteine might be acting as a
      competitive antagonist of the GABAA rho1 receptors.

PMID- 29023776
TI  - Improving Therapeutics to Better Care for Older Adults and the Young: Report From
      the American College of Clinical Pharmacology Workshop.

PMID- 29023775
TI  - Prenatal sonographic monitoring of progressive cardiac damages caused by anti-Ro
      antibodies: A case report.
AB  - Maternal autoantibodies to Ro/SSA are often linked to congenital heart block and
      rarely associated with structural defects. We describe the case of a fetus with
      anti-Ro-mediated second-degree block at 19 weeks, which progressed to a complete
      block, fibroelastosis, atrioventricular valve insufficiency, and semilunar valve
      stenosis/insufficiency at 20, 22, 24, and 26 weeks, respectively, although the
      fetus received transplacental anti-arrhythmic drugs. The 2150-g fetus was
      vaginally delivered at 35 weeks. An external pacemaker was inserted immediately
      after birth and replaced with permanent pacemaker at the age of 3 months. The
      newborn has had a good outcome with well-controlled heart rate.

PMID- 29023777
TI  - Self- and informant perceptions of psychopathic traits in relation to the
      triarchic model.
AB  - OBJECTIVE: The validity of self-report psychopathy measures may be undermined by
      characteristics thought to be defining features of the construct, including poor
      self-awareness, pathological lying, and impression management. The current study
      examined agreement between self- and informant perceptions of psychopathic traits
      captured by the triarchic model (Patrick, Fowler, & Krueger, 2009) and the extent
      to which psychopathic traits are associated with socially desirable responding.
      METHOD: Participants were undergraduate roommate dyads (N = 174; Mage  = 18.9
      years; 64.4% female; 59.8% Caucasian) who completed self- and informant reports
      of boldness, meanness, and disinhibition. RESULTS: Self-reports of psychopathic
      traits reasonably aligned with the perceptions of informants (rs = .36-.60), and
      both predicted various types of antisocial behaviors, although some associations
      were only significant for monomethod correlations. Participants viewed by
      informants as more globally psychopathic did not engage in greater positive
      impression management. However, this response style significantly correlated with
      self- and informant-reported boldness, suppressing associations with antisocial
      behavior. CONCLUSIONS: These findings suggest that participants are willing and
      able to disclose psychopathic personality traits in research settings under
      conditions of confidentiality. Nonetheless, accounting for response style is
      potentially useful when using self-report measures to examine the nature and
      correlates of psychopathic traits.

PMID- 29023774
TI  - Transmission of a common intestinal neoplasm in zebrafish by cohabitation.
AB  - Intestinal neoplasms are common in zebrafish (Danio rerio) research facilities.
      These tumours are most often seen in older fish and are classified as small cell
      carcinomas or adenocarcinomas. Affected fish populations always contain
      subpopulations with preneoplastic lesions, characterized by epithelial
      hyperplasia or inflammation. Previous observations indicated that these tumours
      are unlikely caused by diet, water quality or genetic background, suggesting an
      infectious aetiology. We performed five transmission experiments by exposure of
      naive fish to affected donor fish by cohabitation or exposure to tank effluent
      water. Intestinal lesions were observed in recipient fish in all exposure groups,
      including transmissions from previous recipient fish, and moribund fish exhibited
      a higher prevalence of neoplasms. We found a single 16S rRNA sequence, most
      similar to Mycoplasma penetrans, to be highly enriched in the donors and exposed
      recipients compared to unexposed control fish. We further tracked the presence of
      the Mycoplasma sp. using a targeted PCR test on individual dissected intestines
      or faeces or tank faeces. Original donor and exposed fish populations were
      positive for Mycoplasma, while corresponding unexposed control fish were
      negative. This study indicates an infectious aetiology for these transmissible
      tumours of zebrafish and suggests a possible candidate agent of a Mycoplasma
      species.

PMID- 29023778
TI  - The importance of prenatal 3-dimensional sonography in a case of a segmental
      overgrowth syndrome with unclear chromosomal microarray results.
AB  - PIK3CA-related overgrowth spectrum, caused by mosaic mutations in the PIK3CA
      gene, is associated with regional or generalized asymmetric overgrowth of the
      body or a body part in addition to other clinical findings. Three-dimensional
      ultrasonography (3-D US) has the capability to display structural abnormalities
      in soft tissues or other organs, thereby facilitating identification of segmental
      overgrowth lesions. We present a case suspected of having a segmental overgrowth
      disorder based on 3-D US, whose chromosomal microarray result was abnormal, but
      apparently was not the cause of the majority of the fetus's clinical features.

PMID- 29023779
TI  - A new system for classifying tooth, root and canal anomalies.
AB  - Understanding the normal anatomical features as well as the more unusual
      developmental anomalies of teeth, roots and root canals is essential for
      successful root canal treatment. In addition to various types of root canal
      configuration and accessory canal morphology, a wide range of developmental
      tooth, root and canal anomalies exists, including C-shaped canals, dens
      invaginatus, taurodontism, root fusion, dilacerations and palato-gingival
      grooves. There is a direct association between developmental anomalies and pulp
      and periradicular diseases that usually require a multidisciplinary treatment
      approach to achieve a successful outcome. A number of classifications have
      categorized tooth, root and canal anomalies; however, several important details
      are often missed making the classifications less than ideal and potentially
      confusing. Recently, a new coding system for classifying root, root canal and
      accessory canal morphology has been introduced. The purpose of this article is to
      introduce a new system for classifying tooth, root and canal anomalies for use in
      research, clinical practice and training, which can serve as complementary codes
      to the recently described system for classifying root, as well as main and
      accessory canal morphology.

PMID- 29023780
TI  - Quantitative analysis of multiple elements in healthy and remodeled epithelium
      from human upper airway mucosa using nuclear microscopy.
AB  - Elements are vital in airway mucosal physiology and pathology, but their
      distribution and levels in the mucosa remain unclear. This study uses the state
      of-the-art nuclear microscopy facility to map and quantify multiple elements in
      the histology sections of nasal mucosa from patients with nasal polyps or
      inverted papilloma. Our results demonstrate that P and Ca are the most abundant
      elements in mucosa and their distinct difference between epithelial and
      subepithelial regions; more importantly, our results reveal decreased amounts of
      Cu and Zn in the remodeled epithelium as compared to the normal epithelium. These
      findings suggest that Cu and Zn may be beneficial targets to regulate aberrant
      epithelial remodeling in airway inflammation.

PMID- 29023781
TI  - Cleaning of used rotary nickel-titanium files in an ultrasonic bath by locally
      intensified acoustic cavitation.
AB  - AIM: To compare the pre-sterilization cleaning of rotary Ni-Ti files of different
      sizes previously used a. ex vivo and b. clinically by a washer-disinfector, a
      regular ultrasonic bath, and the same ultrasonic bath in combination with a
      recently developed cavitation intensifying method. METHODOLOGY: Two sets of two
      hundred rotary Ni-Ti files, one previously used ex vivo and another one used
      clinically, were collected from the undergraduate and postgraduate clinics of the
      Academic Centre for Dentistry Amsterdam (ACTA). The instruments were immersed in
      an enzymatic solution and subsequently cleaned either by a washer-disinfector, a
      regular ultrasonic bath combined with a glass beaker, the same bath combined with
      a beaker lined with two cavitation intensifying sheets or with two standard
      plastic sheets. The positive control consisted of used files that did not undergo
      any cleaning and the negative control included new unused files. The instruments
      were then stained to reveal remaining protein material and scored under a
      stereoscopic microscope. The results were analysed by nonparametric statistical
      tests (alpha = 0.05). RESULTS: No significant difference was found between the
      combination of the ultrasonic bath and the regular glass beaker and the same
      ultrasonic bath with the beaker lined with the cavitation intensifying sheets.
      The washer-disinfector left significantly more debris compared to the latter
      group when clinically used files were evaluated (P <= 0.001). The effect of
      instrument size on cleaning was not consistent. CONCLUSION: None of the tested
      methods was able to remove all residual protein material from the files; however,
      it could be noted that this study did not follow the reprocessing protocol
      provided by the manufacturer.

PMID- 29023782
TI  - Perceptions of animal-assisted interventions: The influence of attitudes toward
      companion animals.
AB  - OBJECTIVE: We tested whether people are prone toward positive perceptions of
      Animal-Assisted Interventions (AAIs). We additionally evaluated whether this
      effect is stronger for people who have positive attitudes toward companion
      animals. METHOD: We presented 210 participants with fictitious news reports, each
      describing a study of an AAI or a control intervention. Participants rated the
      news reports on their credibility, acceptability, and general appeal and
      completed a measure of attitudes toward companion animals. RESULTS: Individuals
      with positive attitudes toward companion animals evaluated AAIs as more credible,
      acceptable, and positive than did individuals with negative attitudes toward
      companion animals. There was no difference in how people with positive and
      negative attitudes toward companion animals evaluated control treatments.
      CONCLUSION: We found that individuals with positive attitudes toward companion
      animals perceived AAIs as more credible, acceptable, and positive, relative to
      individuals with more negative attitudes toward companion animals.

PMID- 29023783
TI  - Melatonin application in targeting oxidative-induced liver injuries: A review.
AB  - It is believed that oxidative stress is a key causing factor of liver damage
      induced by a variety of agents, and it is a major contributing factor in almost
      all conditions compromising liver function, including ischemia-reperfusion injury
      (IRI), nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis
      (NASH), liver fibrosis, liver cirrhosis, and hepatocellular carcinoma (HCC).
      Liver is the organ that high concentration of melatonin (N-acetyl-5
      methoxytryptamine) accumulates, and it is the sole organ where circulating
      melatonin is metabolized. Melatonin is one of the best antioxidants that protects
      liver, and its metabolites also have antioxidative function. Melatonin exerts its
      antioxidative function directly through its radical scavenging ability and
      indirectly through stimulation of antioxidant enzymes. The antioxidative response
      from melatonin in liver affects from various factors, including its dosage,
      route, time and duration of administration, the type of oxidative-induced agent
      and species aging. This indoleamine is also an effective and promising
      antioxidative choice for targeting liver IRI, NAFLD, NASH, fibrosis, cirrhosis,
      and HCC.

PMID- 29023785
TI  - CNS synapses are stabilized trans-synaptically by laminins and laminin
      interacting proteins.
AB  - The retina expresses several laminins in the outer plexiform layer (OPL), where
      they may provide an extracellular scaffold for synapse stabilization. Mice with a
      targeted deletion of the laminin beta2 gene (Lamb2) exhibit retinal disruptions:
      photoreceptor synapses in the OPL are disorganized and the retinal physiological
      response is attenuated. We hypothesize that laminins are required for proper
      trans-synaptic alignment. To test this, we compared the distribution, expression,
      association and modification of several pre- and post-synaptic elements in wild
      type and Lamb2-null retinae. A potential laminin receptor, integrin alpha3, is at
      the presynaptic side of the wild-type OPL. Another potential laminin receptor,
      dystroglycan, is at the post-synaptic side of the wild-type OPL. Integrin alpha3
      and dystroglycan can be co-immunoprecipitated with the laminin beta2 chain,
      demonstrating that they may bind laminins. In the absence of the laminin beta2
      chain, the expression of many pre-synaptic components (bassoon, kinesin, among
      others) is relatively undisturbed although their spatial organization and
      anchoring to the membrane is disrupted. In contrast, in the Lamb2-null, beta
      dystroglycan (beta-DG) expression is altered, co-localization of beta-DG with
      dystrophin and the glutamate receptor mGluR6 is disrupted, and the post-synaptic
      bipolar cell components mGluR6 and GPR179 become dissociated, suggesting that
      laminins mediate scaffolding of post-synaptic components. In addition, although
      pikachurin remains associated with beta-DG, pikachurin is no longer closely
      associated with mGluR6 or alpha-DG in the Lamb2-null. These data suggest that
      laminins act as links among pre- and post-synaptic laminin receptors and alpha-DG
      and pikachurin in the synaptic space to maintain proper trans-synaptic alignment.

PMID- 29023784
TI  - Plasma membrane Ca2+ -ATPase 1 is required for maintaining atrial Ca2+
      homeostasis and electrophysiological stability in the mouse.
AB  - KEY POINTS: The role of plasma membrane Ca2+ -ATPase 1 (PMCA1) in Ca2+
      homeostasis and electrical stability in atrial tissue has been investigated at
      both organ and cellular levels in mice with cardiomyocyte-specific deletion of
      PMCA1 (PMCA1cko ) The PMCA1cko hearts became more susceptible to atrial
      arrhythmic stress conditions than PMCA1loxP/loxP hearts. PMCA1 deficiency alters
      cellular Ca2+ homeostasis under both baseline and stress conditions. PMCA1 is
      required for maintaining cellular Ca2+ homeostasis and electrical stability in
      murine atria under stress conditions. ABSTRACT: To determine the role of plasma
      membrane Ca2+ -ATPase 1 (PMCA1) in maintaining Ca2+ homeostasis and electrical
      stability in the atrium under physiological and stress conditions, mice with a
      cardiomyocyte-specific deletion of PMCA1 (PMCA1cko ) and their control
      littermates (PMCA1loxP/loxP ) were studied at the organ and cellular levels. At
      the organ level, the PMCA1cko hearts became more susceptible to atrial
      arrhythmias under rapid programmed electrical stimulation compared with the
      PMCA1loxP/loxP hearts, and such arrhythmic events became more severe under Ca2+
      overload conditions. At the cellular level, the occurrence of irregular-type
      action potentials of PMCA1cko atrial myocytes increased significantly under Ca2+
      overload conditions and/or at higher frequency of stimulation. The decay of Na+
      /Ca2+ exchanger current that followed a stimulation protocol was significantly
      prolonged in PMCA1cko atrial myocytes under basal conditions, with Ca2+ overload
      leading to even greater prolongation. In conclusion, PMCA1 is required for
      maintaining Ca2+ homeostasis and electrical stability in the atrium. This is
      particularly critical during fast removal of Ca2+ from the cytosol, which is
      required under stress conditions.

PMID- 29023786
TI  - Response to flecainide test in Andersen-Tawil syndrome with incessant ventricular
      tachycardia.

PMID- 29023787
TI  - Percutaneous transapical approach and transcatheter closure for ventricular
      tachycardia ablation.
AB  - In patients with mechanical aortic and mitral valve prosthesis, left ventricular
      endocardial ablation via retrograde transaortic or antegrade transmitral approach
      carry high risk of catheter entrapment and death. In such cases, ablation can be
      performed via ventricular transseptal or transapical approach. Transapical
      approach, with the ease of catheter maneuverability and better endocardial
      contact, may be performed surgically or percutaneously. In this case report, we
      describe a patient with both aortic and mitral mechanical prosthesis who
      underwent ventricular tachycardia ablation via percutaneous transapical
      endocardial approach with the use of closure device.

PMID- 29023788
TI  - New initiative: Patient and clinical education (PACE) pages.

PMID- 29023789
TI  - Evaluation of the efficiency of three extraction conditions for the
      immunochemical detection of allergenic soy proteins in different food matrices.
AB  - BACKGROUND: Recent studies have shown the need to improve soy allergen extraction
      using different extraction conditions to ensure more accurate results in allergen
      detection. This study investigated some of these extraction conditions to confirm
      that these methods, especially ultrasound-assisted extraction (UAE) and the use
      of Laemmli buffer instead of the conventional extraction with phosphate-buffered
      saline (PBS), could be helpful in improving the extraction step in allergen
      detection. RESULTS: Higher total soluble protein was obtained in all samples
      extracted with Laemmli buffer alone and in combination with ultrasound. For
      immunochemical detection of soy proteins by enzyme-linked immunosorbent assay
      (ELISA), comparable detection was observed in extracts from all extraction
      conditions in all commercial samples with the exception of table cracker and
      veggie burger, where significantly higher detection was seen in extracts from
      Laemmli buffer only. For the dry mix and cookie samples, the degree of soy
      protein detection with ELISA varied among the different extraction conditions,
      but overall, extraction with only Laemmli buffer showed higher detection.
      CONCLUSION: Laemmli buffer with conventional extraction and UAE may be better
      alternatives or additional extraction methods in soy allergen detection.
      Different food matrices performed differently (whether it was for the recovery of
      total proteins or detection by ELISA) under different extraction conditions. (c)
      2017 Society of Chemical Industry.

PMID- 29023791
TI  - Application of computed tomography and stereolithography to correct a complex
      angular and torsional limb deformity in a donkey.
AB  - OBJECTIVE: To report the evaluation, surgical planning, and outcome for
      correction of a complex limb deformity in the tibia of a donkey using computed
      tomographic (CT) imaging and a 3D bone model. STUDY DESIGN: Case report. ANIMALS:
      A 1.5-year-old, 110 kg donkey colt with an angular and torsional deformity of the
      right pelvic limb. METHODS: Findings on physical examimation included a severe,
      complex deformity of the right pelvic limb that substantially impeded ambulation.
      Both hind limbs were imaged via CT, and imaging software was used to characterize
      the bone deformity. A custom stereolithographic bone model was printed for
      preoperative planning and rehersal of the surgery. A closing wedge ostectomy with
      de-rotation of the tibia was stabilized with 2 precontoured 3.5-mm locking
      compression plates. Clinical follow-up was available for 3.5 years
      postoperatively. RESULTS: CT allowed characterization of the angular and
      torsional bone deformity of the right tibia. A custom bone model facilitated
      surgical planning and rehearsal of the procedure. Tibial corrective ostectomy was
      performed without complication. Postoperative management included physical
      rehabilitation to help restore muscular function and pelvic limb mechanics. Short
      term and long-term follow-up confirmed bone healing and excellent clinical
      function. CONCLUSION: CT imaging and stereolithography facilitated the evaluation
      and surgical planning of a complex limb deformity. This combination of techniques
      may improve the accuracy of the surgeons' evaluation of complex bone deformities
      in large animals, shorten operating times, and improve outcomes.

PMID- 29023790
TI  - Adult multipotent stromal cell cryopreservation: Pluses and pitfalls.
AB  - Study and clinical testing of adult multipotent stromal cells (MSCs) are central
      to progressive improvements in veterinary regenerative medicine. Inherent
      limitations to long-term culture preclude use for storage. Until cell line
      creation from primary isolates becomes routine, MSC stasis at cryogenic
      temperatures is required for this purpose. Many protocols and reagents, including
      cryoprotectants, used for veterinary MSCs are derived from those for human and
      rodent cells. Dissimilarities in cryopreservation strategies play a role in
      variable MSC behaviors. Familiarity with contemporary cryopreservation reagents
      and processes is essential to an appreciation of their impact on MSC survival and
      post-cryopreservation behavior. In addition to these points, this review includes
      a brief history and description of current veterinary stem cell regulation.

PMID- 29023792
TI  - Rebuttal from Thomas E. DeCoursey.

PMID- 29023793
TI  - CrossTalk proposal: Proton permeation through HV 1 requires transient protonation
      of a conserved aspartate in the S1 transmembrane helix.

PMID- 29023794
TI  - Attenuation of oxidative stress and artificial wound closure in C2C12 myoblasts
      induced by sequential extracts of Boerhavia diffusa.
AB  - OBJECTIVES: Whole plants of Boerhavia diffusa L. are widely used medicine in
      Ghana and other tropical countries, for the treatment of wounds and other
      ailments. The aim of the study was to determine the ability of sequential
      extracts of B. diffusa to influence oxidation and wound closure in myoblast cells
      in vitro. METHODS: Sequential extracts were prepared from the whole plant using
      four solvents of increasing polarity (hexane, ethyl acetate, methanol and water).
      Cytotoxicity was determined using the sulforhodamine B staining assay, phase
      contrast microscopy, plasDIC microscopy and live-dead staining. Extracts were
      tested for their ability to reduce 2,2'-azobis(2-amidinopropane) dihydrochloride
      (AAPH)-induced oxidation and mediate cell migration after artificial wound
      generation in C2C12 myoblast cells using the scratch wound assay. KEY FINDINGS:
      All extracts indicated negligible cytotoxicity (IC50  > 100 MUg/ml), and
      microscopic evaluation showed no difference from negative controls. AAPH induced
      a 2.87-fold increase in reactive oxygen species compared to the negative control.
      Pretreatment with 100 MUg/ml of the extracts reduced AAPH-induced oxidation to
      1.70-fold of the untreated controls (P < 0.001). Wound closures in the methanol
      and water extract treatments were 18.08% and 20.76% higher than the negative
      control, respectively (P < 0.01). CONCLUSIONS: These findings indicate that the
      hexane, methanol and water extracts of B. diffusa whole plant promote artificial
      wound healing and protection against oxidation in vitro and therefore warrant
      further research into its mechanisms of wound healing.

PMID- 29023795
TI  - Real-Time ECG Simulation for Hybrid Mock Circulatory Loops.
AB  - Classically, mock circulatory loops only simulate mechanical properties of the
      circulation. To connect the hydraulic world with electrophysiology, we present a
      real-time electrical activity model of the heart and show how to integrate this
      model into a real-time mock loop simulation. The model incorporates a predefined
      conduction pathway and a simplified volume conductor to solve the bidomain
      equations and the forward problem of electrocardiography, resulting in a
      physiological simulation of the electrocardiogram (ECG) at arbitrary electrode
      positions. A complete physiological simulation of the heart's excitation would be
      too CPU intensive. Thus, in our model, complexity was reduced to allow real-time
      simulation of ECG-triggered medical systems in vitro; this decreases time and
      cost in the development process. Conversely, the presented model can still be
      adapted to various pathologies by locally changing the properties of the heart's
      conduction pathway. To simulate the ECG, the heart is divided into suitable
      areas, which are innervated by the hierarchically structured conduction system.
      To distinguish different cardiac regions, a segmentation of the heart was
      performed. In these regions, Prim's algorithm was applied to identify the
      directed minimal spanning trees for conduction orientation. Each node of the tree
      was assigned to a cardiac action potential generated by its hybrid automaton to
      represent the heart's conduction system by the spatial distribution of action
      potentials. To generate the ECG output, the bidomain equations were implemented
      and a simple model of the volume conductor of the body was used to solve the
      forward problem of electrocardiography. As a result, the model simulates
      potentials at arbitrary electrode positions in real-time. To verify the developed
      real-time ECG model, measurements were made within a hybrid mock circulatory
      loop, including a simple ECG-triggered ventricular assist device control. The
      model's potential value is to simulate physiological and pathological behavior
      for hardware-in-the-loop testing of medical devices in an ECG-triggered scenario.

PMID- 29023796
TI  - Hemodynamic parameters and baroreflex sensitivity during head-up tilt test in
      patients with neurally mediated syncope.
AB  - BACKGROUND: We aimed to investigate differences in hemodynamic parameters and the
      role of baroreflex sensitivity (BRS) in patients with a history of neurally
      mediated syncope (NMS) compared with a control group. METHODS: Hemodynamic
      parameters and BRS were continuously measured noninvasively using a Finometer at
      rest and during passive head-up tilt test (HUT) in patients with a history of NMS
      (n = 55) and a control group (n = 77). The tilting period was divided into
      pretest (resting supine position), initial (first 3 minutes of tilting), last
      (last 3 minutes of tilting), and recovery (3 minutes after tilting was complete)
      periods. RESULTS: Decrease in systolic blood pressure (- 14.7 +/- 15.7 mm Hg vs -
      7.6 +/- 14.3 mm Hg, P < 0.01) was more prominent and increase in total systemic
      peripheral resistance was significantly smaller (67.6 +/- 418.7 dyn.s/cm5 vs
      189.4 +/- 261.0 dyn.s/cm5 , P = 0.04) from the initial to the last period of HUT
      in the patient group compared with the control group. BRS was significantly
      higher during the pretest period (20.1 +/- 10.9 ms/mm Hg vs 13.0 +/- 8.1 ms/mm
      Hg, P < 0.01) in the patient group, while the decrease in BRS from the pretest to
      the initial period was greater (-8.5 +/- 6.0 ms/mm Hg vs - 3.2 +/- 4.1 ms/mm Hg,
      P = 0.01). CONCLUSIONS: Dysfunctional BRS in response to orthostatic stress might
      be involved in pathological autonomic cardiac modulation of NMS.

PMID- 29023799
TI  - miR-214 activates TP53 but suppresses the expression of RELA, CTNNB1, and STAT3
      in human cervical and colorectal cancer cells.
AB  - High Mobility Group AT-hook 1 (HMGA1) was identified as a target of miR-214 in
      human cervical and colorectal cancers (CaCx and CRC) in a previous study. While
      the expression of miR-214 remains suppressed, HMGA1 behaves as a potent oncogene
      and plays crucial roles in several aberrant signalling pathways by interacting
      with intermediates like RELA, CTNNB1, STAT3, and TP53 in CaCx and CRC.
      Hypothetically, miR-214 should be able to regulate the stabilization of some of
      these intermediates through the regulation of HMGA1. This was assessed by
      ectopically expressing miR-214 or complementarily, by inhibiting the expression
      of HMGA1. In promoter luciferase assays, miR-214 inhibited NF-kappaB and Wnt
      activities but elevated TP53 activity in cancer cells. Further, miR-214
      suppressed the expression of HMGA1, RELA, CTNNB1, and STAT3 while elevating TP53
      levels, similar to when small interfering RNA (siRNA) against HMGA1 was used, as
      revealed by Western blotting. It is suggested that poor expression of miR-214,
      commonly reported in CaCx and CRC tissues, may not only result in the sustained
      expression of HMGA1 but also that of RELA, CTNNB1, and STAT3, and a congruent
      suppression of TP53 during cancer initiation/progression. These several states
      are, however, reversed when miR-214 is reintroduced and could explain the tumour
      suppressive functions observed in earlier studies. Further studies are, however,
      required to reveal how microRNA-mediated regulation of HMGA1 expression may
      affect individual signalling pathways in CaCx and CRC. Current results reveal
      that miR-214 is not only able to regulate the expression of its direct target,
      HMGA1, but also that of a few signalling intermediates like TP53, RELA, CTNNB1,
      and STAT3, with which HMGA1 interacts. These intermediates play crucial roles in
      signalling pathways commonly deregulated in human CaCx and CRC. Hence, it is
      proposed that miR-214 might act as a tumour suppressor by regulating several
      aberrant signalling pathways through HMGA1. This knowledge has the potential to
      help design novel therapeutic strategies in CaCx and CRC.

PMID- 29023800
TI  - To pace or not to pace: a pilot study of four- and five-gaited Icelandic horses
      homozygous for the DMRT3 'Gait Keeper' mutation.
AB  - The Icelandic horse is a breed known mainly for its ability to perform the
      ambling four-beat gait 'tolt' and the lateral two-beat gait pace. The natural
      ability of the breed to perform these alternative gaits is highly desired by
      breeders. Therefore, the discovery that a nonsense mutation (C>A) in the DMRT3
      gene was the main genetic factor for horses' ability to perform gaits in addition
      to walk, trot and canter was of great interest. Although several studies have
      demonstrated that homozygosity for the DMRT3 mutation is important for the
      ability to pace, only about 70% of the homozygous mutant (AA) Icelandic horses
      are reported to pace. The aim of the study was to genetically compare four- and
      five-gaited (i.e. horses with and without the ability to pace) AA Icelandic
      horses by performing a genome-wide association (GWA) analysis. All horses (n =
      55) were genotyped on the 670K Axiom Equine Genotyping Array, and a GWA analysis
      was performed using the genabel package in r. No SNP demonstrated genome-wide
      significance, implying that the ability to pace goes beyond the presence of a
      single gene variant. Despite its limitations, the current study provides
      additional information regarding the genetic complexity of pacing ability in
      horses. However, to fully understand the genetic differences between four- and
      five-gaited AA horses, additional studies with larger sample materials and
      consistent phenotyping are needed.

PMID- 29023798
TI  - Intrathecal antibody distribution in the rat brain: surface diffusion,
      perivascular transport and osmotic enhancement of delivery.
AB  - KEY POINTS: It is unclear precisely how macromolecules (e.g. endogenous proteins
      and exogenous immunotherapeutics) access brain tissue from the cerebrospinal
      fluid (CSF). We show that transport at the brain-CSF interface involves a balance
      between Fickian diffusion in the extracellular spaces at the brain surface and
      convective transport in perivascular spaces of cerebral blood vessels.
      Intrathecally-infused antibodies exhibited size-dependent access to the
      perivascular spaces and tunica media basement membranes of leptomeningeal
      arteries. Perivascular access and distribution of full-length IgG could be
      enhanced by intrathecal co-infusion of hyperosmolar mannitol. Pores or stomata
      present on CSF-facing leptomeningeal cells ensheathing blood vessels in the
      subarachnoid space may provide unique entry sites into the perivascular spaces
      from the CSF. These results illuminate new mechanisms likely to govern antibody
      trafficking at the brain-CSF interface with relevance for immune surveillance in
      the healthy brain and insights into the distribution of therapeutic antibodies.
      ABSTRACT: The precise mechanisms governing the central distribution of
      macromolecules from the cerebrospinal fluid (CSF) to the brain and spinal cord
      remain poorly understood, despite their importance for physiological processes
      such as antibody trafficking for central immune surveillance, as well as several
      ongoing intrathecal clinical trials. In the present study, we clarify how IgG and
      smaller single-domain antibodies (sdAb) distribute throughout the whole brain in
      a size-dependent manner after intrathecal infusion in rats using ex vivo
      fluorescence and in vivo three-dimensional magnetic resonance imaging. Antibody
      distribution was characterized by diffusion at the brain surface and widespread
      distribution to deep brain regions along the perivascular spaces of all vessel
      types, with sdAb accessing a four- to seven-fold greater brain area than IgG.
      Perivascular transport involved blood vessels of all caliber and putative smooth
      muscle and astroglial basement membrane compartments. Perivascular access to
      smooth muscle basement membrane compartments also exhibited size-dependence.
      Electron microscopy was used to show stomata on leptomeningeal coverings of blood
      vessels in the subarachnoid space as potential access points allowing substances
      in the CSF to enter the perivascular space. Osmolyte co-infusion significantly
      enhanced perivascular access of the larger antibody from the CSF, with
      intrathecal 0.75 m mannitol increasing the number of perivascular profiles per
      slice area accessed by IgG by ~50%. The results of the present study reveal
      potential distribution mechanisms for endogenous IgG, which is one of the most
      abundant proteins in the CSF, as well as provide new insights with respect to
      understanding and improving the drug delivery of macromolecules to the central
      nervous system via the intrathecal route.

PMID- 29023801
TI  - Influence of genotype and crop year in the chemometrics of almond and pistachio
      oils.
AB  - BACKGROUND: Almond and pistachio oils can be considered as interesting products
      to produce and commercialize owing to their health-promoting properties. However,
      these properties are not consistent because of the differences that appear in
      oils as a result of the genotype and the crop year. The analysis of these
      variations and their origin is decisive in ensuring the commercial future
      prospects of these nut oils. RESULTS: Although significant variability has been
      reported in almond and pistachio oils as a result of the crop year and the
      interaction between crop year and genotype, the genotype itself remains the main
      factor determining oil chemometrics. Oil fatty acid profile has been mainly
      determined by the genotype, with the exception of palmitic fatty acid in
      pistachio oil. However, the crop year affects the concentration of some minor
      components of crucial nutritional interest as total polyphenols and phytosterols.
      CONCLUSION: Regarding reported differences in oil, some almond and pistachio
      genotypes should be prioritized for oil extraction. Breeding programmes focused
      on the improvement of specific characteristics of almond and pistachio oils
      should focus on chemical parameters mainly determined by the genotype. (c) 2017
      Society of Chemical Industry.

PMID- 29023802
TI  - A novel 12-bp indel polymorphism within the GDF9 gene is significantly associated
      with litter size and growth traits in goats.

PMID- 29023804
TI  - Apnea induction for invasive lung function testing in infant olive baboons:
      Comparison of intravenous propofol versus hyperventilation.
AB  - BACKGROUND: In various types of pulmonary research, pulmonary function testing
      (PFT) is performed to quantify the severity of lung disease. Induction of apnea
      and positive pressure ventilation are required for accurate PFT measurements in
      non-cooperative subjects. We compared two methods of apnea induction in infant
      olive baboons (Papio anubis). METHODS: Pulmonary function testing results were
      compared during apnea induced by hyperventilation (CO2 washout) vs. intravenous
      propofol (1 dose 10 mg/kg). PFT was evaluated using a hot-wire pneumotachometer
      incorporated within an Avea ventilator in nine 1-month-old baboons. RESULTS:
      Propofol induced apnea faster and more reliably. In both groups, PFT values
      passed the statistical equivalence test and were not significantly different
      (Student's t-test). There was a trend toward less data variability after propofol
      administration. CONCLUSIONS: Intravenous propofol was non-inferior to CO2 washout
      for apnea induction in infant olive baboons. Propofol induced apnea faster and
      more reliably and yielded less variable PFT results.

PMID- 29023803
TI  - HBeAg levels at week 24 predict response to 8 years of tenofovir in HBeAg
      positive chronic hepatitis B patients.
AB  - BACKGROUND: Hepatitis B e antigen (HBeAg) seroconversion is a treatment endpoint
      for HBeAg-positive CHB, and a necessary precursor to HBsAg loss. Biomarkers that
      predict serological outcomes would be useful. AIM: To evaluate the utility of
      measuring HBeAg levels for predicting HBeAg seroconversion and HBsAg loss under
      long-term tenofovir (TDF) therapy. METHODS: A total of 266 patients were enrolled
      into a phase III study of TDF vs adefovir (ADV) for 48 weeks in HBeAg-positive
      patients, followed by open-label TDF up to 384 weeks. Serum HBeAg levels were
      measured for subjects with samples available at both baseline and week 24 of
      treatment (n = 200). Analysis compared subjects who achieved HBeAg seroconversion
      by week 384 vs no HBeAg seroconversion. RESULTS: HBeAg seroconversion rate was
      52% by week 384. Time to HBeAg seroconversion was 80 weeks (IQR: 36-162). HBeAg
      decline at week 24 was associated with HBeAg seroconversion (1.63 vs 0.90 log10
      PEIU/mL, P = .002). The optimal threshold for identifying HBeAg seroconversion
      was HBeAg decline >=2.2 log10 PEIU/mL at week 24, with HBeAg seroconversion
      achieved by 76% of patients, compared to 44% if HBeAg decline <2.2 log10 (P <
      .0001). HBeAg decline >=2.2 log10 PEIU/mL at week 24 was associated with HBsAg
      loss in genotype A or D patients (38% vs 15%, P = .03). Precore/basal core
      promotor variants were associated with lower baseline HBeAg levels, but not HBeAg
      seroconversion. CONCLUSION: Decline in HBeAg levels by week 24 was associated
      with HBeAg seroconversion and HBsAg loss in HBeAg-positive chronic hepatitis B
      patients treated with long-term TDF.

PMID- 29023806
TI  - The percutaneous toxicokinetics of VX in a damaged skin porcine model and the
      evaluation of WoundStatTM as a topical decontaminant.
AB  - This study used a damaged skin, porcine model to evaluate the in vivo efficacy of
      WoundStatTM for the decontamination of superficial, nerve agent-contaminated
      wounds. Anaesthetized animals were randomly assigned to either control (n = 7),
      no decontamination (n = 12) or WoundStatTM (n = 12) treatment groups. Pigs were
      exposed to a 5* LD50 dose of neat, radiolabelled S-[2-(diisopropylamino)ethyl]-O
      ethyl methyl-phosphonothioate (VX; or equivalent volume of sterile saline for the
      control group) via an area of superficially damaged skin on the ear. WoundStatTM
      was applied at 30 seconds post-exposure to assigned animals. The VX contaminant
      (or saline) and decontaminant remained in place for the duration of the study (up
      to 6 hours). Physiological parameters and signs of intoxication were recorded
      during the exposure period. Skin and organ samples were taken post mortem for 14
      C-VX distribution analyses. Blood samples were taken periodically for
      toxicokinetic and whole-blood acetylcholinesterase (AChE) activity analyses. VX
      exposure was accompanied by a rapid decrease in AChE activity in all animals,
      regardless of decontamination. However, decontamination significantly improved
      survival rate and time and reduced the severity of signs of intoxication. In
      addition, the distribution of 14 C-VX in key internal organs and post mortem
      blood samples was significantly lower in the WoundStatTM treatment group. This
      study demonstrates that WoundStatTM may be a suitable medical countermeasure for
      increasing both survival rate and time following VX exposure. The results also
      suggest that AChE activity is not a useful prognostic indicator.

PMID- 29023805
TI  - Intracranial source activity (eLORETA) related to scalp-level asymmetry scores
      and depression status.
AB  - Frontal EEG alpha asymmetry provides a promising index of depression risk, yet
      very little is known about the neural sources of alpha asymmetry. To identify
      these sources, this study examined alpha asymmetry using a distributed inverse
      solution: exact low resolution brain electromagnetic tomography (eLORETA).
      Findings implicated a generator in lateral midfrontal regions that contributed to
      both surface asymmetry and depression risk. Participants with any lifetime
      history of depressive episodes were characterized by less left than right
      activity in the precentral gyrus and midfrontal gyrus. Anhedonia accounted for a
      significant portion of the relationship between alpha asymmetry and lifetime
      major depressive disorder. Results are suggestive of convergence between
      motivational and capability models of asymmetry and replicate results from
      experimental studies in a large resting-state data set. The capability model of
      frontal alpha asymmetry is contextualized in terms of motor preparedness
      following emotional mobilization.

PMID- 29023807
TI  - Application of rape pod sealants to reduce adverse environmental impacts.
AB  - BACKGROUND: Rape (Brassica napus L.) is a major global oilseed crop characterized
      by its high potential as an alimentary oil and in biodiesel production. The two
      most popular pod sealants (PS) used to reduce rape pod shattering are products in
      the pinolene range (di-1-p-menthene) and latex polymer products. Reports on the
      effective preservation of seed yield by these products are fairly contradictory.
      With this in mind, an experimental PS (PS4) that contained the active agents
      acrylic and trisiloxane was developed. RESULTS: Comparative experimental trials
      of the developed PS4 and three other PS (PS1, PS2 and PS3) containing active
      agents that are generally used for sealant production were conducted. The studies
      showed that the static and dynamic surface tension of PS4 was the lowest at the
      same concentration (2.0 g kg-1 ), consequently demonstrating the lowest spray
      drift. The chemical substances from PS had not penetrated the rape seeds in any
      of the PSs. CONCLUSION: The results indicate that treatment with PS4 exerts a
      beneficial effect in reducing rape seed yield loss (68-104 kg ha-1 in 2014 and
      194-305 kg ha-1 in 2015) compared to other investigated PS. (c) 2017 Society of
      Chemical Industry.

PMID- 29023808
TI  - Enhancement of the water solubility and antioxidant activity of hesperidin by
      chitooligosaccharide.
AB  - BACKGROUND: Hesperidin is a natural product and a strong antioxidant with
      potential applications in various food and pharmaceutical products. However, its
      poor water solubility greatly limits its applications. RESULTS: In this study,
      chitooligosaccharide (COS) was applied to prepare a stable complex with
      hesperidin (Hesp-COS) via the spray-drying method at 100  degrees C for 20 min.
      The resultant complex was characterized by Fourier transformation infrared
      spectroscopy, thermogravimetric analysis, scanning electron microscopy and proton
      nuclear magnetic resonance spectroscopy. It was demonstrated that the aromatic
      rings of hesperidin interacted with COS through hydrogen bonding and formed Hesp
      COS complex. As a result, both the water solubility and antioxidant activity of
      Hesp-COS were higher than that of the free hesperidin. CONCLUSION: The
      preparation conditions of Hesp-COS in this study were efficient and produced an
      increment in both the water solubility and antioxidant activity of hesperidin.
      (c) 2017 Society of Chemical Industry.

PMID- 29023809
TI  - A nucleotide substitution in exon 8 of the glucosylceramidase beta gene is
      associated with Gaucher disease in sheep.

PMID- 29023810
TI  - Development of functional extruded snacks by utilizing paste shrimp (Acetes
      spp.): process optimization and quality evaluation.
AB  - BACKGROUND: Functional extruded snacks were prepared using paste shrimp powder
      (Acetes spp.), which is rich in protein. The process variables required for the
      preparation of extruded snacks was optimized using response surface methodology.
      Extrusion temperature (130-144  degrees C), level of Acetes powder (100-200 g kg
      1 ) and feed moisture (140-200 g kg-1 ) were selected as design variables, and
      expansion ratio, porosity, hardness, crispness and thiobarbituric acid reactive
      substance value were taken as the response variables. RESULTS: Extrusion
      temperature significantly influenced all the response variables, while Acetes
      inclusion influenced all variables except porosity. Feed moisture content showed
      a significant quadratic effect on all responses and an interactive effect on
      expansion ratio and hardness. Shrimp powder incorporation increased the protein
      and mineral content of the final product. The extruded snack made with the
      combination of extrusion temperature 144.59  degrees C, feed moisture 178.5 g kg
      1 and Acetes inclusion level 146.7 g kg-1 was found to be the best one based on
      sensory evaluation. CONCLUSION: The study suggests that use of Acetes species for
      the development of extruded snacks will serve as a means of utilization of Acetes
      as well as being a rich source of proteins for human consumption, which would
      otherwise remain unexploited as a by-catch. (c) 2017 Society of Chemical
      Industry.

PMID- 29023811
TI  - Placental growth factor inhibition targets pulmonary angiogenesis and represents
      a therapy for hepatopulmonary syndrome in mice.
AB  - : Hepatopulmonary syndrome (HPS) is a severe complication of cirrhosis with
      increased risk of mortality. Pulmonary microvascular alterations are key features
      of HPS; but underlying mechanisms are incompletely understood, and studies on HPS
      are limited to rats. Placental growth factor (PlGF), a proangiogenic molecule
      that is selectively involved in pathological angiogenesis, may play an important
      role in HPS development; however, its role has never been investigated. In this
      study, we validated an HPS model by common bile duct ligation (CBDL) in mice,
      investigated the kinetic changes in pulmonary angiogenesis and inflammation
      during HPS development, and provide evidence for a novel therapeutic strategy by
      targeting pathological angiogenesis. Mice with CBDL developed hypoxemia and
      intrapulmonary shunting on a background of liver fibrosis. Pulmonary alterations
      included increased levels of proangiogenic and inflammatory markers, which was
      confirmed in serum of human HPS patients. Increased PlGF production in HPS mice
      originated from alveolar type II cells and lung macrophages, as demonstrated by
      immunofluorescent staining. Dysfunctional vessel formation in CBDL mice was
      visualized by microscopy on vascular corrosion casts. Both prophylactic and
      therapeutic anti-PlGF (alphaPlGF) antibody treatment impeded HPS development, as
      demonstrated by significantly less intrapulmonary shunting and improved gas
      exchange. alphaPlGF treatment decreased endothelial cell dysfunction in vivo and
      in vitro and was accompanied by reduced pulmonary inflammation. Importantly,
      alphaPlGF therapy did not affect liver alterations, supporting alphaPlGF's
      ability to directly target the pulmonary compartment. CONCLUSION: CBDL in mice
      induces HPS, which is mediated by PlGF production; alphaPlGF treatment improves
      experimental HPS by counteracting pulmonary angiogenesis and might be an
      attractive therapeutic strategy for human HPS. (Hepatology 2017).

PMID- 29023812
TI  - Polycystic liver disease: Hepatic venous outflow obstruction lesions of the
      noncystic parenchyma have major consequences.
AB  - : In patients with polycystic liver disease (PLD), development of cysts induces
      hepatic venous outflow obstruction (HVOO) and parenchymal modifications,
      challenging the paradigm of a normal noncystic liver parenchyma. The aims were to
      reappraise the pathology of the noncystic parenchyma, by focusing on HVOO
      lesions; and to investigate the association with outflow obstruction at imaging
      and perioperative course after liver resection. This is a retrospective study
      conducted in one tertiary center between 1993 and 2014. PLD patients (n = 125)
      who underwent resection (n = 90) or transplantation (n = 35) were included. HVOO
      parenchymal lesions were assessed for all patients and a liver congestion score
      was built. Imaging was analysed for 45 patients with computed tomography scan,
      and perioperative course was assessed in resected patients. At pathology, 92% of
      patients had HVOO lesions, with sinusoidal dilatation being the most common
      feature. HVOO was more severe in patients who underwent transplantation compared
      to liver resection, as assessed by the congestion score. At imaging, all patients
      had HVOO with at least two hepatic veins involved. Mosaic enhancement pattern of
      the parenchyma was associated with the severity of hepatic vein obstruction (P =
      0.045) and the compression of the inferior vena cava (P = 0.014). In case of
      liver resection, intraoperative course was characterized by hemorrhage, related
      to HVOO at imaging. Ascites (44%) and liver failure (9%) in the postoperative
      period were associated with blood losses and transfusions. CONCLUSION: Hepatic
      venous outflow obstruction, including development of venous collaterality and
      parenchymal changes, is frequent in PLD and has major consequences on
      intraoperative bleeding and postoperative ascites and liver failure. Hepatic
      venous outflow obstruction should be taken into account to choose the most
      appropriate surgical treatment. (Hepatology 2017).

PMID- 29023814
TI  - Oral bleeding associated with palatine erosion in the cat.

PMID- 29023815
TI  - Polysaccharides in Spirulina platensis Improve Antioxidant Capacity of Chinese
      Style Sausage.
AB  - : This study examined the effect of Spirulina platensis polysaccharides (SPP) at
      0.1%, 0.25%, and 0.5% (wt/wt) of Chinese-style sausages on lipid peroxidation,
      microbiological and sensory properties during 24 d stored at 4  degrees C. During
      the storage, pH, lightness (L* ) values, DPPH radical scavenging activity and
      sensory scores decreased with time and TBARS, TVB-N, mesophilic, and
      psychrotrophic total viable counts increased. However, the magnitude of the
      changes was attenuated with the addition of SPP as compared to control. Samples
      containing SPP had significantly (P <= 0.05) higher DPPH radical scavenging
      activity and lower TBARS values compared with the control, and the antioxidant
      effect was dose-dependent. The addition of 0.5% SPP maintained stable redness (a*
      ) values of sausages, although there was no positive effect on the
      microbiological status. Moreover, the addition of SPP prevented the decrease of
      aroma, flavor and sensory acceptance of samples. The results suggested
      incorporation of SPP could decrease lipid peroxidation and improve sensory
      properties of Chinese-style sausage. PRACTICAL APPLICATION: There is a great need
      for adding natural antioxidants to healthier meat and meat products. Spirulina
      platensis polysaccharides (SPP) had strong antioxidant activity. The addition of
      SPP to Chinese-style pork sausage could inhibit lipid peroxidation, to extend the
      shelf life of meat products. SPP were very potential to be used to replace
      synthetic antioxidants in meat and meat products.

PMID- 29023813
TI  - Dual catenin loss in murine liver causes tight junctional deregulation and
      progressive intrahepatic cholestasis.
AB  - : beta-Catenin, the downstream effector of the Wnt signaling, plays important
      roles in hepatic development, regeneration, and tumorigenesis. However, its role
      at hepatocyte adherens junctions (AJ) is relatively poorly understood, chiefly
      due to spontaneous compensation by gamma-catenin. We simultaneously ablated beta-
      and gamma-catenin expression in mouse liver by interbreeding beta-catenin-gamma
      catenin double-floxed mice and Alb-Cre transgenic mice. Double knockout mice show
      failure to thrive, impaired hepatocyte differentiation, cholemia, ductular
      reaction, progressive cholestasis, inflammation, fibrosis, and tumorigenesis,
      which was associated with deregulation of tight junctions (TJ) and bile acid
      transporters, leading to early morbidity and mortality, a phenotype reminiscent
      of progressive familial intrahepatic cholestasis (PFIC). To address the
      mechanism, we specifically and temporally eliminated both catenins from
      hepatocytes using adeno-associated virus 8 carrying Cre-recombinase under the
      thyroid-binding globulin promoter (AAV8-TBG-Cre). This led to a time-dependent
      breach of the blood-biliary barrier associated with sequential disruption of AJ
      and TJ verified by ultrastructural imaging and intravital microscopy, which
      revealed unique paracellular leaks around individual hepatocytes, allowing mixing
      of blood and bile and leakage of blood from one sinusoid to another. Molecular
      analysis identified sequential losses of E-cadherin, occludin, claudin-3, and
      claudin-5 due to enhanced proteasomal degradation, and of claudin-2, a beta
      catenin transcriptional target, which was also validated in vitro. CONCLUSION: We
      report partially redundant function of catenins at AJ in regulating TJ and
      contributing to the blood-biliary barrier. Furthermore, concomitant hepatic loss
      of beta- and gamma-catenin disrupts structural and functional integrity of AJ and
      TJ via transcriptional and posttranslational mechanisms. Mice with dual catenin
      loss develop progressive intrahepatic cholestasis, providing a unique model to
      study diseases such as PFIC. (Hepatology 2018;67:2320-2337).

PMID- 29023816
TI  - Effects of dietary hop (Humulus lupulus L.) beta-acids on quality attributes,
      composition and oxidative stability of pork meat.
AB  - BACKGROUND: The effects of dietary levels of hop beta-acids on physical
      attributes, lipid oxidation and chemical composition of pork meat were evaluated.
      Thirty-two castrated male pigs obtained from a complete block design feeding
      experiment (6.23 +/- 0.42 kg initial body weight (BW) to 20.45 +/- 0.95 kg final
      BW) and fed diets supplemented with 0, 120, 240 or 360 mg kg-1 hop beta-acids
      during 35 days were slaughtered to sample longissimus dorsi muscle for meat
      analysis. RESULTS: No effects (P > 0.05) of dietary hop beta-acids were observed
      on meat physical attributes. Quadratic effects (P < 0.05) of hop beta-acids were
      observed on lipid and protein contents and on thiobarbituric acid-reactive
      substance (TBARS) values of meatballs, whose equations allowed the estimation of
      dietary hop beta-acid levels of 176, 169 and 181 mg kg-1 to provide up to 16.20%
      lipid reduction, 1.95% protein accretion and 23.31% TBARS reduction respectively.
      CONCLUSION: Dietary hop beta-acids fed to pigs might reduce lipid, increase
      protein and reduce lipid oxidation without affecting physical attributes of the
      pork meat. (c) 2017 Society of Chemical Industry.

PMID- 29023817
TI  - Changes in polyphenol profile of dried apricots containing SO2 at various
      concentrations during storage.
AB  - BACKGROUND: Changes in polyphenols have important effects on the quality
      (especially color) and health benefits of dried apricots. SO2 concentration,
      storage and the activities of polyphenol oxidase (PPO) and phenylalanine ammonia
      lyase (PAL) were factors which had significant effects on polyphenols. Polyphenol
      profile and activities of PPO and PAL in sulfured dried apricots (SDAs, 0, 451,
      832, 2112 and 3241 mg SO2 kg-1 ) were monitored during storage at 4, 20 and 30 
      degrees C for 379 days for the first time. RESULTS: Even the lowest SO2
      concentration (451 mg kg-1 ) was sufficient to inactivate PPO during the entire
      storage period. However, while SO2 led to the increase in PAL activity of the
      samples (r = 0.767) before storage, PAL activities of SDAs decreased during
      storage. After 90 days of storage, PAL activity was determined in only non
      sulfured dried apricots (NSDAs) and dried apricots containing 451 mg SO2 kg-1 .
      Although the major polyphenol in NSDAs was epicatechin (611.4 mg kg-1 ), that in
      SDAs was chlorogenic acid (455-1508 mg kg-1 ), followed by epicatechin (0-426.8
      mg kg-1 ), rutin (148.9-477.3 mg kg-1 ), ferulic acid (23.3-55.3 mg kg-1 ) and
      gallic acid (2.4-43.6 mg kg-1 ). After storage at 30  degrees C for 379 days, the
      major polyphenol in SDAs was gallic acid (706-2324 mg kg-1 ). However, the major
      polyphenol in NSDAs did not change after storage. The highest total polyphenol
      content was detected in SDAs containing 2112 mg SO2 kg-1 and stored at 30 
      degrees C. CONCLUSION: To produce dried apricots having high polyphenol content,
      ~2000 mg SO2 kg-1 should be used. Low storage temperature (<30  degrees C) was
      not necessary for the protection of polyphenols. (c) 2017 Society of Chemical
      Industry.

PMID- 29023818
TI  - Commentary on Montag et al. (2017): The Importance of CBPR in FASD Prevention
      with American Indian Communities.

PMID- 29023820
TI  - Neuron-Specific Enolase: Is It Enough?

PMID- 29023819
TI  - Nonalcoholic fatty liver disease impairs expression of the type II inositol 1,4,5
      trisphosphate receptor.
AB  - : Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease
      worldwide. It may result in several types of liver problems, including impaired
      liver regeneration (LR), but the mechanism for this is unknown. Because LR
      depends on calcium signaling, we examined the effects of NAFLD on expression of
      the type II inositol 1,4,5-trisphosphate receptor (ITPR2), the principle calcium
      release channel in hepatocytes. ITPR2 promoter activity was measured in Huh7 and
      HepG2 cells. ITPR2 and c-Jun protein levels were evaluated in Huh7 cells, in
      liver tissue from a rat model of NAFLD, and in liver biopsy specimens of patients
      with simple steatosis and nonalcoholic steatohepatitis (NASH). LR was assessed in
      wild-type and Itpr2 knockout (Itpr2-/- ) mice following 67% hepatectomy. Cell
      proliferation was examined in ITPR2-knockout HepG2 cells generated by the
      CRISPR/Cas9 system. c-Jun dose dependently decreased activity of the human ITPR2
      promoter. c-Jun expression was increased and ITPR2 was decreased in fat-loaded
      Huh7 cells and in livers of rats fed a high-fat, high-fructose diet.
      Overexpression of c-Jun reduced protein and mRNA expression of ITPR2 in Huh7
      cells, whereas knockdown of c-Jun prevented the decrease of ITPR2 in fat-loaded
      Huh7 cells. ITPR2 expression was decreased and c-Jun was increased in liver
      biopsies of patients with steatosis and NASH compared to controls. ITPR2-knockout
      cells exhibited less nuclear calcium signaling and cell proliferation than
      control cells. LR assessed by Ki-67 and proliferating cell nuclear antigen was
      markedly decreased in Itpr2-/- mice. CONCLUSION: Fatty liver induces a c-Jun
      mediated decrease in ITPR2 in hepatocytes. This may account for the impaired LR
      that occurs in NAFLD. (Hepatology 2017).

PMID- 29023821
TI  - Optimization of coronary sinus lead placement targeted to the longest right-to
      left delay in patients undergoing cardiac resynchronization therapy: The Optimal
      Pacing SITE 2 (OPSITE 2) acute study and protocol.
AB  - AIMS: Left ventricular (LV) lead positioning at the site of delayed electrical
      activation is associated with better response to cardiac resynchronization
      therapy (CRT). We hypothesized that a long electrical conduction delay between
      right ventricular (RV) and coronary sinus (CS) leads during RV pacing (RLD index)
      is correlated with a better clinical outcome METHODS AND RESULTS: RLD is measured
      intraprocedurally, during RV pacing, as the time interval between the
      intracardiac electrograms of RV and CS leads. Initially, we did a prove-of
      concept, feasibility, acute study in 97 patients who underwent CRT implantation.
      The CS lead position was assessed in the 40 degrees  right anterior oblique and
      40 degrees  left anterior oblique views and assigned to one of 11 prespecified
      segments of a schematic eyeball depiction of the LV walls. Acute outcomes were
      QRS width during biventricular (BIV) pacing. The longest RLD were found in the
      basal and mid lateral segments; these accounted for 82% and 78%, respectively, of
      the total QRS width (%RLD). %RLD was inversely correlated with BIV-paced QRS (P 
      =  0.0001). A similar slope was present either in the 78 patients with preserved
      atrioventricular (AV) conduction and in the 19 without AV conduction (- 0.34 vs -
      0.27, P  =  0.7). CONCLUSION: We showed that RLD can be used to guide lead
      placement at the time of CRT implantation and that it is correlated with BIV-QRS
      width, an indirect predictor of clinical outcome. Based on these findings we
      started the prospective, multicenter Optimal Pacing SITE 2 (OPSITE 2) trial with
      the objective to demonstrate a relationship between RLD and clinical outcomes
      assessed as death, hospitalization for heart failure, New York Heart Association
      class, and clinical composite score. The protocol is provided.

PMID- 29023823
TI  - Is attention enhanced following performance errors? Testing the adaptive control
      hypothesis.
AB  - The present study tested whether people adaptively sharpen attentional focus
      following performance mistakes, as predicted by current theories of cognitive
      control. Participants completed a reverse Stroop task in which target stimuli
      were preceded by an informative spatial cue. Cue validity and Stroop interference
      effects on performance were robust, but neither effect was altered by commission
      of an error on the prior trial, as predicted by the adaptive control model.
      Likewise, a prior error did not enhance cue-evoked spatial asymmetries in EEG,
      nor did it enhance validity effects on neural responses evoked by targets.
      Instead, errors were followed by poorer overall performance and generalized
      arousal, as measured by generally suppressed EEG alpha power in postresponse and
      cue-to-target intervals following errors compared to correct responses. Results
      support an alternative theory that post-error changes in neural activity and
      performance reflect arousal, orienting, or cognitive bottlenecking rather than
      adaptive control of attention.

PMID- 29023822
TI  - The context of coping: a qualitative exploration of underlying inequalities that
      influence health services support for people living with long-term conditions.
AB  - Coping with chronic illness encapsulates both practical and emotional aspects of
      living life in relation to one's long-term health condition(s). Dominant health
      psychology approaches for understanding coping, which underpin a more recent
      policy discourse on 'self-management', focus sharply on the person affected by
      illness and potentially mask the influence of overarching social structure. In
      this paper we draw on qualitative interviews with 48 people living with long-term
      conditions (LTCs), in order to highlight the role that structural configurations
      such as healthcare systems may play in either helping or hindering people's
      efforts to cope with chronic illness. We argue that coping is a social process in
      which health and related services, situated within their wider political-economic
      contexts, play an active role in shaping people's attempts to live well with
      LTCs. More specifically, health systems are sites of social and cultural capital
      exchange that can differentially mobilise coping resources through access,
      continuity of care, and coordination across services. Whilst it is essential to
      recognise the personal agency of people living with chronic illness, it is also
      vital to acknowledge the underlying inequalities that affect the ways in which
      services can support such resourcefulness.

PMID- 29023825
TI  - GenIce: Hydrogen-Disordered Ice Generator.
AB  - GenIce is an efficient and user-friendly tool to generate hydrogen-disordered ice
      structures. It makes ice and clathrate hydrate structures in various file
      formats. More than 100 kinds of structures are preset. Users can install their
      own crystal structures, guest molecules, and file formats as plugins. The
      algorithm certifies that the generated structures are completely randomized
      hydrogen-disordered networks obeying the ice rule with zero net polarization. (c)
      2017 The Authors. Journal of Computational Chemistry Published by Wiley
      Periodicals, Inc.

PMID- 29023826
TI  - Cystic fibrosis transmembrane conductance regulator: Actin(g) as a master
      regulator of cholangiocyte function.

PMID- 29023824
TI  - Cholangiocyte autophagy contributes to hepatic cystogenesis in polycystic liver
      disease and represents a potential therapeutic target.
AB  - : Polycystic liver disease (PLD) is a group of genetic disorders with limited
      treatment options and significant morbidity. Hepatic cysts arise from
      cholangiocytes exhibiting a hyperproliferative phenotype. Considering that
      hyperproliferation of many cell types is associated with alterations in
      autophagy, we hypothesized that autophagy is altered in PLD cholangiocytes,
      contributes to hepatic cystogenesis, and might represent a potential therapeutic
      target. We employed functional pathway cluster analysis and next-generation
      sequencing, transmission electron microscopy, immunofluorescence confocal
      microscopy, and western blotting to assess autophagy in human and rodent PLD
      cholangiocytes. A three-dimensional culture model was used to study the effects
      of molecular and pharmacologic inhibition of autophagy on hepatic cystogenesis in
      vitro, and the polycystic kidney disease-specific rat, an animal model of PLD, to
      study the effects of hydroxychloroquine, a drug that interferes with the
      autophagy pathway, on disease progression in vivo. Assessment of the
      transcriptome of PLD cholangiocytes followed by functional pathway cluster
      analysis revealed that the autophagy-lysosomal pathway is one of the most altered
      pathways in PLD. Direct evaluation of autophagy in PLD cholangiocytes both in
      vitro and in vivo showed increased number and size of autophagosomes, lysosomes,
      and autolysosomes; overexpression of autophagy-related proteins (Atg5, Beclin1,
      Atg7, and LC3); and enhanced autophagic flux associated with activation of the
      cAMP-protein kinase A-cAMP response element-binding protein signaling pathway.
      Molecular and pharmacologic intervention in autophagy with ATG7 small interfering
      RNA, bafilomycin A1 , and hydroxychloroquine reduced proliferation of PLD
      cholangiocytes in vitro and growth of hepatic cysts in three-dimensional
      cultures. Hydroxychloroquine also efficiently inhibited hepatic cystogenesis in
      the polycystic kidney disease-specific rat. CONCLUSION: Autophagy is increased in
      PLD cholangiocytes, contributes to hepatic cystogenesis, and represents a
      potential therapeutic target for disease treatment. (Hepatology 2018;67:1088
      1108).

PMID- 29023827
TI  - TNFalpha and IL-17A are differentially expressed in psoriasis-like vs eczema-like
      drug reactions to TNFalpha antagonists.
AB  - BACKGROUND: Tumor necrosis factor alpha (TNFalpha) blocking drugs are in use for
      a wide range of autoimmune disorders. In up to 5% of patients, this class of
      drugs produces puzzling cutaneous side effects that are the subject of this
      investigation, namely psoriasiform and eczema-like skin inflammation. These side
      effects can occur after any time of treatment and regardless of the underlying
      disorders. The exact pathophysiology is as yet unknown. METHODS: A total of 33
      patients (19 female, average age 52 years) who had a cutaneous reaction to
      infliximab, adalimumab or etanercept were included. The type of inflammatory
      reaction was determined, and the corresponding cytokine expression was evaluated
      by immunohistochemistry for TNFalpha, IL-1beta, IL-22, IL-6, IL-17A, IL33, IL-8
      and IL-36alpha (semi-quantitative grading system from - to ++++). In addition,
      RNA expression levels of IL-17A and TNFalpha were confirmed by quantitative real
      time PCR. RESULTS: IL-17A (P < .039) and TNFalpha (P < .008) were expressed at
      significantly higher levels in psoriasis or pustular-like reactions (PPR)
      compared to eczematous-like reactions (ELR). There was no significant difference
      in the expression of IL-1beta, IL-22, IL-6, IL-33, IL-8 and IL-36alpha between
      PPR and ELR. CONCLUSION: TNFalpha and IL-17A are both cytokines known to be
      involved in psoriasis but less so in non-psoriasiform dermatitis or eczema.
      Therefore, their overexpression in PPR is plausible and suggests that the
      pathogenesis of PPR mirrors at least in part those of psoriasis. Further
      investigations will define the exact role of these cytokines in rare cutaneous
      side effects of anti-TNFalpha therapy. Our results suggest that IL-17A inhibition
      could be a therapeutic option in patients with anti-TNF induced psoriasis.

PMID- 29023829
TI  - Application of Quantitative Pharmacology Approaches in Bridging Pharmacokinetics
      and Pharmacodynamics of Domagrozumab From Adult Healthy Subjects to Pediatric
      Patients With Duchenne Muscular Disease.
AB  - Domagrozumab, a monoclonal antibody that binds to myostatin, is being developed
      for Duchenne muscular dystrophy (DMD) boys following a first-in-human study in
      healthy adults. Literature reporting pharmacokinetic parameters of monoclonal
      antibodies suggested that body-weight- and body-surface-area-adjusted clearance
      and volume of distribution estimates between adults and children are similar for
      subjects older than 6 years. Population modeling identified a Michaelis-Menten
      binding kinetics model to optimally characterize the target mediated drug
      disposition profile of domagrozumab and identified body mass index on the volume
      of distribution as the only significant covariate. Model parameters were
      predicted with high-precision pharmacokinetics (clearance 1.01 * 10-4 L/[h.kg];
      central volume of distribution 457 * 10-4 L/kg; maximum elimination rate 17.5 *
      10-4 nmol/[h.kg], Km 10.6 nmol/L) and pharmacodynamics (myostatin turnover rate
      457 * 10-4 h-1 ; complex removal rate 90 * 10-4 h-1 ; half-saturation constant
      4.32 nmol/L) and were used to predict target coverage for dosage selection in the
      DMD population. Additionally, allometric approaches (estimated scaling exponents
      (standard error) for clearance and volume were 0.81 [0.01] and 0.98 [0.02],
      respectively) in conjunction with a separate analysis to obtain the population
      mean weight and standard deviation suggested that if dosed per body weight, an
      only 11% difference in clearance is expected between the heaviest and lightest
      patient, thus preventing the need for dose adjustment. In summary, quantitative
      approaches were instrumental in bridging and derisking the fast-track development
      of domagrozumab in DMD.

PMID- 29023828
TI  - Impact of surveillance for hepatocellular carcinoma on survival in patients with
      compensated cirrhosis.
AB  - : Surveillance for hepatocellular carcinoma (HCC) has been recommended in
      patients with cirrhosis. In this study, we examined the extent to which the
      competing risk of hepatic decompensation influences the benefit of HCC
      surveillance by investigating the impact of availability of liver transplantation
      (LTx) and the rate of progression of hepatic decompensation on survival gain from
      HCC surveillance. A multistate Markov model was constructed simulating a cohort
      of 50-year-old patients with compensated cirrhosis. The primary outcome of
      interest was all-cause and HCC-specific mortality. The main input data included
      incidence of HCC, sensitivity of screening test, and mortality from hepatic
      decompensation. Treatment modalities modeled included LTx, resection, and
      radiofrequency ablation. In the base case scenario, LTx would be available to
      prevent death in a certain proportion of patients. In the absence of
      surveillance, 68.2% of the cohort members died within 15 years; of these
      decedents, 25.1% died from HCC and 43.6% died from hepatic decompensation. With
      surveillance, the median survival improved from 10.4 years to 11.2 years. The
      number of subjects under surveillance needed to reduce one all-cause and one HCC
      specific death over 15 years was 28 and 18, respectively. In sensitivity
      analyses, incidence of HCC and progression of cirrhosis had the strongest effect
      on the benefit of surveillance, whereas LTx availability had a negligible effect.
      CONCLUSION: HCC surveillance decreases all-cause and tumor-specific mortality in
      patients with compensated cirrhosis regardless of LTx availability. In addition,
      incidence of HCC and sensitivity of surveillance test also had a substantial
      impact on the benefits of surveillance. (Hepatology 2018;68:78-88).

PMID- 29023831
TI  - Photochemistry and Photophysics of the 3-Styrylidenebenz[e]indanes.
AB  - The photochemical and photophysical properties of the extended conformers of
      trans- and cis-1-(2-naphthyl)-2-phenylethenes (t- and c-NPEB ) are strikingly
      different than those of their rigid analogues, trans- and cis-3
      styrylidenebenz[e]indane (t- and c-BPE). The fluorescence quantum yield and
      lifetime at 25 degrees C in methylcyclohexane drop from 0.76 and 22.2 ns in t
      NPEB to 0.0051 and 0.25 ns in t-BPE, and there are complementary changes in the
      photoisomerization quantum yields. In both cases, photoisomerization occurs in S2
      , a stilbenic excited state. The differences in behavior are traced to the
      diminished S1 /S2 energy gap on the alkyl substitution afforded by the five
      membered ring in BPE. The effect of viscosity on the torsional relaxation of t
      BPE, evaluated in glycerol/methanol mixtures at 25 degrees C and in 95/5 and
      99.9/0.1 glycerol/methanol (% v/v) as a function of T, is well accounted for by
      the medium-enhanced barrier model. Absorption and fluorescence spectra of t-BPE
      in pure glycerol reveal aggregate formation. Quenching of t-BPE fluorescence in
      methylcyclohexane by tri-n-butylamine (TBA) leads to exciplex fluorescence.
      Comparison with analogous results for t-NPEB suggests that charge transfer
      involves primarily the naphthalenic S1 state in t-NPEB and the stilbenic S2 state
      in t-BPE.

PMID- 29023832
TI  - Pupil dilation indicates the coding of past prediction errors: Evidence for
      attentional learning theory.
AB  - The attentional learning theory of Pearce and Hall () predicts more attention to
      uncertain cues that have caused a high prediction error in the past. We examined
      how the cue-elicited pupil dilation during associative learning was linked to
      such error-driven attentional processes. In three experiments, participants were
      trained to acquire associations between different cues and their appetitive
      (Experiment 1), motor (Experiment 2), or aversive (Experiment 3) outcomes. All
      experiments were designed to examine differences in the processing of
      continuously reinforced cues (consistently followed by the outcome) versus
      partially reinforced, uncertain cues (randomly followed by the outcome). We
      measured the pupil dilation elicited by the cues in anticipation of the outcome
      and analyzed how this conditioned pupil response changed over the course of
      learning. In all experiments, changes in pupil size complied with the same basic
      pattern: During early learning, consistently reinforced cues elicited greater
      pupil dilation than uncertain, randomly reinforced cues, but this effect
      gradually reversed to yield a greater pupil dilation for uncertain cues toward
      the end of learning. The pattern of data accords with the changes in prediction
      error and error-driven attention formalized by the Pearce-Hall theory.

PMID- 29023830
TI  - Drug management in acute kidney disease - Report of the Acute Disease Quality
      Initiative XVI meeting.
AB  - AIMS: To summarize and extend the main conclusions and recommendations relevant
      to drug management during acute kidney disease (AKD) as agreed at the 16th Acute
      Disease Quality Initiative (ADQI) consensus conference. METHODS: Using a modified
      Delphi method to achieve consensus, experts attending the 16th ADQI consensus
      conference reviewed and appraised the existing literature on drug management
      during AKD and identified recommendations for clinical practice and future
      research. The group focussed on drugs with one of the following characteristics:
      (i) predominant renal excretion; (ii) nephrotoxicity; (iii) potential to alter
      glomerular function; and (iv) presence of metabolites that are modified in AKD
      and may affect other organs. RESULTS: We recommend that medication reconciliation
      should occur at admission and discharge, at AKD diagnosis and change in AKD
      phase, and when the patient's condition changes. Strategies to avoid adverse drug
      reactions in AKD should seek to minimize adverse events from overdosing and
      nephrotoxicity and therapeutic failure from under-dosing or incorrect drug
      selection. Medication regimen assessment or introduction of medications during
      the AKD period should consider the nephrotoxic potential, altered renal and
      nonrenal elimination, the effects of toxic metabolites and drug interactions and
      altered pharmacodynamics in AKD. A dynamic monitoring plan including repeated
      serial assessment of clinical features, utilization of renal diagnostic tests and
      therapeutic drug monitoring should be used to guide medication regimen
      assessment. CONCLUSIONS: Drug management during different phases of AKD requires
      an individualized approach and frequent re-assessment. More research is needed to
      avoid drug associated harm and therapeutic failure.

PMID- 29023833
TI  - High School Students' Recommendations to Improve School Food Environments:
      Insights From a Critical Stakeholder Group.
AB  - BACKGROUND: The Healthy, Hunger-Free Kids Act of 2010 (HHFKA) directed the US
      Department of Agriculture (USDA) to revise school meal standards. Students are
      most affected by efforts to improve the school food environment; yet, few studies
      directly include students. This study examined high school students' experiences
      of school meal reform to gain insight into implementation recommendations.
      METHODS: We conducted 5 focus groups with high school students (N = 15) from high
      schools across 9 states. We also conducted follow-up interviews to further
      explore personal experiences. Focus groups and interview transcripts were coded
      and organized in Atlas.ti v7 by analysts, following principles of constant
      comparative analysis. RESULTS: Students reported overall positive perceptions of
      the revised school meal standards and supported continued efforts to improve the
      food environment. Recommendations to improve the food environment included
      engaging students, focusing on the quality and palatability of meal items, moving
      toward scratch-cooking, and addressing cafeteria infrastructure. CONCLUSIONS:
      Students' recommendations point to opportunities where school districts, as well
      as local, state, and federal organizations can work to improve the school food
      environment. Their insights are directly relevant to USDA's recently released
      Local School Wellness Policy final rule, of which school meal standards are one
      provision.

PMID- 29023834
TI  - Mixed-Methods Evaluation of a Healthy Exercise, Eating, and Lifestyle Program for
      Primary Schools.
AB  - BACKGROUND: Reversing decline in physical fitness and increase in excess body
      weight in school children are considered major public health challenges. We
      evaluated a proposed model to integrate a screening and healthy exercise, eating,
      and lifestyle program (HEELP) into primary schools in Canberra, Australia.
      Objectives were: (1) to establish body status and physical competencies of 5- to
      10-year-old children; (2) to evaluate the service's impact on body status and
      physical fitness; and (3) to gauge parent/guardian and school perspectives on the
      service. METHODS: A mixed-methods approach was used over 4 school years, 2010
      2013. Primary evaluation used direct quantitative measurement. Confirmatory
      qualitative methods were implemented in the last 2 years. RESULTS: The service
      was delivered on 71 occasions involving 25 schools; 7750 children were screened
      and 709 completed all aspects of the HEELP evaluation. Over 60% of children
      screened had 2 or more measures that would benefit from remedial intervention.
      CONCLUSIONS: All body status and physical fitness measures showed small
      beneficial changes on a population basis immediately after the HEELP. Further
      benefit did not accrue at 6 months after the program. Semistructured interviews
      with schools and parent/guardian surveys confirmed some beneficial effects
      observed by direct quantitative measurement.

PMID- 29023835
TI  - School-Based Health Centers and Adolescent Substance Use: Moderating Effects of
      Race/Ethnicity and Socioeconomic Status.
AB  - BACKGROUND: School-based health centers (SBHCs) have been associated with many
      positive health and academic outcomes. The current study extends previous
      research and examines possible differences in the association between SBHC
      exposure and adolescent alcohol, tobacco, and other drug use by race/ethnicity,
      sex, and socioeconomic status (SES). METHODS: California Healthy Kids Survey data
      from 504 traditional high schools in California were linked with publicly
      available data on SBHCs and school demographics. Multilevel logistic regression
      analyses were conducted controlling for school and individual characteristics.
      RESULTS: Significant interactions suggest that SBHC exposure was inversely
      associated with past 30-day alcohol use, binge drinking, and cigarette and e
      cigarette use among African American youth and negatively associated with
      cigarette and marijuana use among Asian youth, relative to whites. There was also
      a significant interaction between SBHC exposure and parent education for past 30
      day alcohol use and binge drinking. No significant sex interactions were
      observed. CONCLUSIONS: SBHC exposure appears to be inversely related to substance
      use among youth in some ethnic minority groups and youth of lower SES. This may
      have implications regarding SBHC placement and investment. Additional research is
      necessary to understand the mechanisms through which SBHCs may influence
      adolescent substance use and other health behaviors.

PMID- 29023836
TI  - Impact of NFL PLAY 60 Programming on Elementary School Children's Body Mass Index
      and Aerobic Capacity: The NFL PLAY 60 FitnessGram Partnership Project.
AB  - BACKGROUND: We examined the impact of the Fuel Up to Play 60 (FUTP60) program on
      children's body mass index (BMI) and aerobic capacity (AC). METHODS:
      Participation in the FUTP60 and both BMI and AC profiles were collected through
      the NFL PLAY 60 FitnessGram Partnership Project involving over 100 schools from
      22 US states. We specifically examined the distributions of BMI and AC among
      participating versus nonparticipating schools in the 2012-2013 school year.
      Hierarchical linear models tested the impact of participation and availability of
      additional funding for program implementation on the proportions of youth meeting
      FitnessGram health-related fitness standards (ie, Needs Improvement-Health Risk
      [NIHR] and Healthy Fitness Zone [HFZ] categories). RESULTS: After 1 year
      implementing the program, participating schools had lower proportions of boys (
      4.1 +/- 2.0%, p = .04) and girls (-4.5 +/- 2.0%, p = .03) in the NIHR for BMI,
      and lower proportion of girls (-9.7 +/- 4.0%, p = .02) in the NIHR for AC. There
      were no differences in the distributions for the HFZ and the availability of
      additional funding did not alter the relationships (p > .05). CONCLUSIONS: This
      study provides preliminary evidence that participation in the FUTP60 is
      associated with improved profiles of health-related fitness.

PMID- 29023837
TI  - Integrating Health Education in Academic Lessons: Is This the Future of Health
      Education in Schools?

PMID- 29023838
TI  - Association Between Experiencing Relational Bullying and Adolescent Health
      Related Quality of Life.
AB  - BACKGROUND: Bullying is a public health concern for the school-aged population,
      however, the health outcomes associated with the subtype of relational bullying
      are less understood. The purpose of this study was to examine the association
      between relational bullying and health-related quality of life (HRQL) among young
      people. METHODS: This study utilized data from 5335 students aged 11-15 years,
      collected as part of the 2014 Health Behavior in School-aged Children (HBSC)
      study conducted in England. Data were collected through self-completed surveys.
      Multilevel analysis modeled the relationship between relational bullying and
      HRQL. Demographic variables (sex, age, ethnicity, socioeconomic status) and other
      forms of bullying were controlled for. RESULTS: Experiencing relational bullying
      had a significant negative association with HRQL whilst controlling for other
      forms of bullying. Weekly relational bullying resulted in an estimated 5.352 (95%
      confidence interval (CI), -4.178, -6.526) decrease in KIDSCREEN-10 score compared
      with those not experiencing relational bullying. CONCLUSION: Experiencing
      relational bullying is associated with poorer HRQL. The findings question the
      perception of relational bullying as being a predominantly female problem. Girls
      were more likely to report experiencing relational bullying, but the negative
      association with HRQL was equal for boys and girls.

PMID- 29023839
TI  - Effectiveness of a Brief Home Parenting Intervention for Reducing Early Sexual
      Risks Among Latino Adolescents: Salud y Exito.
AB  - BACKGROUND: Teen pregnancy rates and related risks remain elevated among Latino
      teens. We tested the impact on youth sexual behaviors of a brief, culturally
      targeted, bilingual media intervention designed for parents of young adolescents.
      METHODS: Salud y exito (Health & Success) uses dramatic audio stories to model
      positive parenting practices. After completing classroom surveys, 27 urban
      schools in the Northeast and Southwest serving low-income Latino communities were
      randomized so that all families of seventh grade students were sent either: (1)
      booklets on healthy eating and exercise; (2) Salud-50, where families either
      received booklets or the intervention, or (3) Salud-100, where all families
      received the intervention. Postintervention follow-up surveys were conducted at 3
      and 12-months. Multilevel analyses tested intervention effects, controlling for
      sociodemographics. RESULTS: Compared with controls, at 12-months postintervention
      (8th grade spring), youth in Salud-100 report lower sexual risks (touching, AOR
      1.46, CI 1.19-0.84, p < .001; lifetime sex (AOR 0.74, CI 0.61-0.90, p < .01); and
      sex intentions (AOR 0.78, CI 0.63-0.96, p < .05). Consistent with a dose
      response, Salud-50 results are between those from Salud-100 and control schools.
      CONCLUSIONS: Salud y exito is an effective parenting intervention that can
      augment school-based health and sexuality education and help Latino parents
      support their children during early adolescence.

PMID- 29023840
TI  - Associations Between Peer Harassment and School Risk and Protection Profiles.
AB  - BACKGROUND: Peer harassment can have serious implications for students' success
      and well-being, and prevention programs need to consider the school context. This
      study aimed to: (1) identify groups of similar schools based on their risk and
      protective factors and demographic characteristics and (2) examine associations
      between school profiles and students' bullying involvement. METHODS: Data came
      from 505 schools and 122,106 students who completed the 2013 Minnesota Student
      Survey. School-level risk and protective factors and demographic characteristics
      were included in a latent profile analysis (LPA) to identify profiles of schools.
      Multilevel logistic regression was used to assess associations between school
      profiles and peer harassment. RESULTS: Six qualitatively different school
      profiles were identified. Unadjusted models showed that schools with higher
      levels of risk had greater odds of peer harassment. However, after controlling
      for student-level risk and protection, regardless of school-level risk, students
      in metro-area schools with a more diverse student body reported lower odds of
      bullying involvement. CONCLUSIONS: These findings highlight the importance of the
      social environment into peer harassment. In addition to addressing student-level
      risk and protection, larger community factors and norms also need to be taken
      into account for developing, selecting, and implementing the most effective
      approaches to bullying prevention.

PMID- 29023842
TI  - Dropped-head syndrome in a patient under treatment with the MEK inhibitor
      trametinib for NRAS-mutated metastatic melanoma.

PMID- 29023843
TI  - Parameterization of the GPR119 Receptor Agonist AR231453.
AB  - The GPR119 receptor is a class A G protein-coupled receptor expressed mainly in
      pancreatic beta cells. Since GPR119 receptor activation ameliorates Type 2
      Diabetes through an increase in glucose-dependent insulin release, the
      development of new GPR119 receptor agonists would be worthwhile. A better
      understanding of the way agonists interact with the receptor would help to design
      better ligands for the receptor. It also would help to better understand the
      agonist mechanism of action. An understanding of how agonists interact with the
      receptor can be acquired using molecular dynamics simulations, which cannot be
      performed without having force field parameters for the ligand molecule. This
      study presents the development of CHARMM force field parameters for AR231453, the
      prototypical first potent and orally available GPR119 agonist, using the Force
      Field Tool Kit. The parameters are validated through Normal Mode Analysis
      calculations and molecular dynamics simulations in combination with infrared
      spectroscopy. (c) 2017 Wiley Periodicals, Inc.

PMID- 29023841
TI  - A Mixed-Methods Comparison of Classroom Context During Food, Health & Choices, a
      Childhood Obesity Prevention Intervention.
AB  - BACKGROUND: Schools are frequent settings for childhood obesity prevention;
      however, intervention results are mixed. Classroom context may hold important
      clues to improving these interventions. METHODS: We used mixed methods to examine
      classroom context during a curriculum intervention taught by trained instructors
      in fifth grade classrooms. We identified classrooms with high and low buy-in
      using cluster analysis and compared intervention delivery and reception, student
      energy balance-related behavior, and student perceptions about supports and
      barriers to energy balance. RESULTS: Delivery and reception did not differ
      between the groups. Between-group differences in unhealthy behaviors were smaller
      at posttest, due to improvement in low buy-in classes. Although student
      perceptions of supports and barriers to energy balance were similar across
      groups, students in high buy-in classes indicated food preferences as a support
      while students in low buy-in classes indicated food preferences as a barrier.
      Neighborhood environment emerged as a universal barrier. CONCLUSIONS: Trained
      instructors may improve intervention delivery and reception regardless of
      classroom context. Social norms could explain high levels of unhealthy behavior
      in low buy-in classes at baseline; improvement at posttest suggests that the
      curriculum may have motivated change. All children need more strategies and
      supportive policies to overcome a challenging food environment.

PMID- 29023844
TI  - Information on Gas-Phase Diatomic Molecules from Magnetically Induced Current
      Densities.
AB  - Magnetically induced current densities are different for different types of
      chemical bonds, and may help highlight some of their characteristics and stress
      their main differences. The present work considers magnetically induced current
      densities in the bonds of diatomic molecules bonded by covalent bonds as well as
      the gas phase molecules of 1:1 ionic compounds, comparing the current strength
      values and visualizing current density maps. The results show clear-cut
      differences for the different types of bonds (non-polar covalent, polar covalent,
      and ionic), and can also be related to the extent of the covalent or ionic
      character of a bond. For ionic compounds, the results also show relevant
      differences depending on the charges of the ions and on their electron
      configuration (including significant effects from the presence of d electrons in
      the outer shell of the ions). The article presents and analyses the results in
      detail. It is concluded that the magnetically induced current densities
      contribute to the description and interpretation of chemical bonding in diatomic
      molecules. (c) 2017 Wiley Periodicals, Inc.

PMID- 29023846
TI  - Locomotor and skeletal muscle abnormalities in trembler J neuropathic mice.
AB  - INTRODUCTION: Patients with hereditary peripheral neuropathies exhibit
      characteristic deformities of the hands and feet and have difficulty ambulating.
      To examine to what extent neuropathic animals recapitulate these deficits, we
      studied trembler J (TrJ) mice, which model early-onset demyelinating neuropathy.
      METHODS: A cohort of 4-month-old female wild type and neuropathic mice were
      evaluated for locomotor measurements, neuromuscular function, and skeletal muscle
      proteolysis and morphometry. RESULTS: Utilizing the DigiGait imaging system, we
      identified pronounced alterations in forepaw and hindpaw angles and a decrease in
      hindpaw area on the treadmill in neuropathic rodents. Torque production by the
      tibialis anterior (TA) muscle was significantly weakened and was paralleled by a
      decrease in myofiber cross-sectional area and an increase in muscle tissue
      proteolysis. DISCUSSION: Our findings in TrJ mice reflect the phenotypic
      presentation of the human neuropathy in which patients exhibit weakness of the TA
      muscle resulting in foot drop and locomotor abnormalities. Muscle Nerve 57: 664
      671, 2018.

PMID- 29023845
TI  - Aqueous Extract of Gynura Bicolor Attenuated Hepatic Steatosis, Glycative,
      Oxidative, and Inflammatory Injury Induced by Chronic Ethanol Consumption in
      Mice.
AB  - Gynura bicolor leaf aqueous extract (GAE) is rich in phytochemicals including
      phenolic acids, flavonoids, carotenoids, and anthocyanins. Effects of GAE upon
      hepatic injury in mice with chronic ethanol intake were examined. Lieber-DeCarli
      liquid diet with ethanol was used to induce hepatic lipid accumulation,
      oxidative, glycative, and inflammatory injury. GAE at 0.25% or 0.5% was added in
      feeds, and supplied to mice consumed Lieber-DeCarli liquid diet with ethanol for
      6 wk. Blood and liver were collected for analyses. Results showed that ethanol
      increased plasma and hepatic triglyceride and cholesterol content, and affected
      plasma levels of insulin, adiponectin, leptin, and ghrelin. GAE at both doses
      decreased lipid accumulation, and at high dose improved hormones abnormality.
      Histological data revealed that GAE supplement mitigated hepatic lipid deposit.
      Ethanol increased plasma Nepsilon -(carboxyethymethyl)-lysine and pentosidine
      levels. GAE at high doses lowered those glycative factors. Ethanol depleted
      glutathione content, increased CYP2E1 activity and reactive oxygen species
      production, and reduced the activity of glutathione peroxide, glutathione
      reductase and catalase in liver. GAE supplement at both doses reversed these
      alterations and attenuated hepatic oxidative stress. GAE supplement also at both
      doses decreased hepatic inflammatory cytokines release in ethanol treated mice.
      These findings support that leaves of G. bicolor is a functional food with liver
      protective activities against ethanol.

PMID- 29023847
TI  - Buffalo SREBP1: molecular cloning, expression and association analysis with milk
      production traits.

PMID- 29023848
TI  - Folliculocystic and collagen hamartoma of tuberous sclerosis: A new case in a
      female patient and review of literature.
AB  - Folliculocystic and collagen hamartoma (FCCH) of tuberous sclerosis is a rare
      entity described in 2012 by Torrelo et al. with only 8 cases described,
      predominantly in males. It presents since birth or early infancy and in the
      majority of cases is associated with tuberous sclerosis. The hamartoma presents
      as an exophytic plaque and has distinctive histopathological features including
      hair follicles, intact or ruptured epidermal cysts, and an increased number of
      collagen fibers extending to the subcutaneous tissue. Herein we present an
      additional case of this rare entity in an 18-year-old female who met clinical
      criteria for tuberous sclerosis. The patient had an exophytic mass in the left
      temporal area for many years and wanted surgical excision due to its cosmetic
      appearance. Histopathology of the surgical specimen showed a hamartomatous lesion
      with multiple large intact epidermal cysts, hairs and increased thickened
      collagen. The patient has followed up for 1 year after the excision, with no
      recurrence. Additionally, we provide a literature review of known cases of FCCH
      as well as its clinical and histopathological differential diagnosis.

PMID- 29023849
TI  - Effects of Early Cues on the Processing of Chinese Relative Clauses: Evidence for
      Experience-Based Theories.
AB  - We used Chinese prenominal relative clauses (RCs) to test the predictions of two
      competing accounts of sentence comprehension difficulty: the experience-based
      account of Levy () and the Dependency Locality Theory (DLT; Gibson, ). Given that
      in Chinese RCs, a classifier and/or a passive marker BEI can be added to the
      sentence-initial position, we manipulated the presence/absence of classifiers and
      the presence/absence of BEI, such that BEI sentences were passivized subject
      extracted RCs, and no-BEI sentences were standard object-extracted RCs. We
      conducted two self-paced reading experiments, using the same critical stimuli but
      somewhat different filler items. Reading time patterns from both experiments
      showed facilitative effects of BEI within and beyond RC regions, and delayed
      facilitative effects of classifiers, suggesting that cues that occur before a
      clear signal of an upcoming RC can help Chinese comprehenders to anticipate RC
      structures. The data patterns are not predicted by the DLT, but they are
      consistent with the predictions of experience-based theories.

PMID- 29023852
TI  - The changing epidemiology of acute flaccid paralysis warrants a paradigm shift in
      surveillance.

PMID- 29023853
TI  - Antibiotics, gut microbiome and obesity.
AB  - Antibiotics have been hailed by many as "miracle drugs" that have been
      effectively treating infectious diseases for over a century, leading to a marked
      reduction in morbidity and mortality. However, with the increasing use of
      antibiotics, we are now faced not only with the increasing threat of antibiotic
      resistance, but also with a rising concern about potential long-term effects of
      antibiotics on human health, including the development of obesity. The obesity
      pandemic continues to increase, a problem that affects both adults and children
      alike. Disruptions to the gut microbiome have been linked to a multitude of
      adverse conditions, including obesity, type 2 diabetes, inflammatory bowel
      diseases, anxiety, autism, allergies, and autoimmune diseases. This review
      focuses on the association between antibiotics and obesity, and the role of the
      gut microbiome. There is strong evidence supporting the role of antibiotics in
      the development of obesity in well-controlled animal models. However, evidence
      for this link in humans is still inconclusive, and we need further well-designed
      clinical trials to clarify this association.

PMID- 29023854
TI  - Still darkness on the edge of Brugada syndrome.

PMID- 29023855
TI  - Hepatitis C virus infection in Jeddah city, Saudi Arabia: Seroprevalence and
      knowledge.
AB  - The infection rate of the hepatitis C virus (HCV) in Saudi Arabia is among the
      lowest in the world. However, it is likely that poor knowledge and awareness of
      HCV infection could minimize the effectiveness of prevention and control programs
      in the kingdom. Thus, the study objective was to estimate the prevalence of HCV
      infection, and to assess current knowledge about it, in the targeted population.
      Data on 5482 Saudi people attending primary healthcare centers in Jeddah City in
      2014/2015 were analyzed in this cross-sectional study. Questions that covered the
      natural history, risk behavior, and prevention, and treatment of HCV were
      collected using a predesigned questionnaire. HCV seroprevalence was assessed
      using an enzyme-linked immunosorbent assay. HCV prevalence of 0.38% (95%
      confidence interval: 0.22-0.54) was found. The level of knowledge of the natural
      history, risk behavior, and prevention and treatment of HCV was poor among the
      participants. The lowest level of knowledge for all participants pertained to its
      prevention and treatment. The prevalence of HCV was low in Saudi Arabia (0.38%).
      However, adequate knowledge of HCV was lacking. Thus, the need to increase
      knowledge and awareness of HCV in the Saudi population is warranted.

PMID- 29023856
TI  - To do or not to do? plasma exchange and timing of steroid administration in
      progressive multifocal leukoencephalopathy.
AB  - OBJECTIVE: To retrospectively analyze the effect of plasma exchange (PLEX; yes =
      PLEX+ , no = PLEX- ) and steroids administration timing (prophylactically [proST]
      or therapeutically [therST]) on the longitudinal clinical course of patients with
      natalizumab-related progressive multifocal leukoencephalopathy (PML) and full
      blown immune reconstitution inflammatory syndrome (PML-IRIS). METHODS: Clinical
      and radiological data of 42 Italian patients with PML were analyzed. Patient's
      data are available until 12 months after PML diagnosis. PLEX and steroids
      treatment as time-dependent covariates were entered in: (1) a Cox model to
      investigate their impact on full-blown PML-IRIS latency; (2) an analysis of
      variance ANOVA to investigate their impact on IRIS duration; and (3) a linear
      mixed model to assess their impact on the longitudinal clinical course (measured
      by means of Expanded Disability Status Scale [EDSS]). RESULTS: Treatment with
      PLEX was not associated to PML-IRIS latency (hazard ratio [HR] = 1.05; p = 0.92),
      but once IRIS emerged, its duration was significantly longer in patients who
      underwent PLEX (101 vs 54 days in PLEX+ and PLEX- patients; p = 0.028). Receiving
      proST versus therST was not associated to IRIS latency (HR = 0.67; p = 0.39) or
      duration (p = 0.95). Patients who underwent proST had a significantly higher EDSS
      increase during PML (0.09 EDSS points per month; p = 0.04) as compared to those
      who had therST. INTERPRETATION: This study highlights that: (1) caution on the
      use of PLEX should be considered as the current data do not support a beneficial
      effect of PLEX and (2) caution on the early use of steroids is suggested because
      their prophylactic use to prevent full-blown PML-IRIS seems to negatively impact
      on the longitudinal disability course. Ann Neurol 2017;82:697-705.

PMID- 29023858
TI  - Interleukin-1 gene cluster Haplotype analysis in the chronic outcome prediction
      of the Hepatitis B virus infection.
AB  - Hepatitis B virus (HBV) infection is well known as an important cause of the
      chronic liver disease. The screening of the genotype of certain cytokines might
      be helpful to predict the clinical outcome of an HBV infection. The present study
      investigates the relationship between the polymorphism and haplotypes of the
      Interleukin-1 (IL-1) gene family, including IL-1-alpha (IL-1A), IL-1-beta (IL
      1B,) and IL-1 receptor antagonist (IL-1RN), with chronic HBV infection. A total
      of 297 chronic HBV and 333 matched on sex and age control individuals were
      genotyped using the standard sequence-specific-polymerase chain reaction primer
      (SSP-PCR) method. Four different haplotype analysis software packages were
      applied for data interpretation. The results showed excess genotype A1/A1 and
      A2/A2 at IL-1RN (40.2%, 39.9%), C/T at IL-1A-889 (55.6%), and C/C at IL-1B-511
      (41.1%) in controls while A1/A1 at IL-1RN (59.3%), T/T at IL-1B-31 (46.5%), C/T
      at IL-1B + 3953 (65%), in chronic HBV infection cases. A total of 148 haplotypes
      were observed overall (96 in the case group and 89 in the control group). The
      haplotype combination of genotype A1/A1 at IL1-RN along with a C/T for all three
      IL-1B polymorphic positions and either C/T or T/T at the IL-1A-899 position may
      increase the probability of the chronic outcome for the HBV infection.

PMID- 29023857
TI  - Preceding haemorrhagic shock as a detrimental risk factor for respiratory
      distress after excessive allogeneic blood transfusion.
AB  - BACKGROUND AND OBJECTIVES: Whether transfusion-associated circulatory overload
      arises as a simple result of over-transfusion or requires another trigger remains
      unclear. Here, we examined whether respiratory distress could be reproduced by
      massive transfusion alone in an animal model. MATERIALS AND METHODS: A total of
      20 anaesthetized swine were equipped with monitors. Allogeneic blood was obtained
      from 10 donor swine. A 4-stage loading protocol with each stage equivalent to 25%
      of the blood volume (BV) in the recipient swine was then used to infuse
      crystalloid (CR), hydroxyethyl starch (HES) or allogeneic blood (TR) (n = 5
      each). The five remaining animals were subjected to a haemorrhagic shock (HS)
      prior to an allogeneic blood transfusion (TRS). RESULTS: The PaO2 /FiO2 (P/F)
      ratio did not decrease to the level of respiratory distress in either the CR
      group or the HES group after loading with a volume corresponding to 100% of the
      recipient BV. However, the TRS and TR groups exhibited significant reductions in
      the P/F ratio after fluid overloading (227 +/- 29 and 267 +/- 133, respectively).
      Blood transfusion after HS expanded the blood volume, but over-transfusion alone
      did not. HS was accompanied by an increase in the white blood cell count.
      CONCLUSION: The lung and the heart can tolerate volume overloads with HES, CR and
      even transfused blood. However, a preceding HS may induce an inflammatory
      response, making the lung vulnerable to subsequent blood overloads. In this
      study, a preceding haemorrhagic shock mediated respiratory distress following
      massive transfusion in a swine model. (247 words).

PMID- 29023859
TI  - Effects of extremely low frequency magnetic field on the development of tolerance
      to the analgesic effect of morphine in rats.
AB  - This study examined the effects of low frequency magnetic field (MF) on tolerance
      to analgesic effect of morphine in rats. Rats were made tolerant to morphine by
      injecting morphine (10 mg/kg, s) once daily for 8 consecutive days. Rats were
      simultaneously exposed to an MF (50 Hz at 1, 50, and 100 MUT for 30 min) before,
      immediately, or 30 min after injection of morphine, and also exposed to a 0.5, 6,
      12, and 30 Hz at 100 MUT for 30 min before injection of morphine. The percentage
      of maximum possible effect of morphine (% MPE) was measured on the 1st, 4th, and
      8th days by hot plate test. We observed that MF radiation (50 Hz at 1 uT and 30
      Hz at 100 uT) immediately before and MF radiation (50 Hz at 100 uT) after
      morphine injection prevented the development of morphine tolerance compared to
      control. Also, we found that exposure to MF (50 Hz at 1, 50, and 100 uT) 30 min
      after injection of morphine failed to maintain the analgesic effect of morphine.
      Our results showed that exposure to low frequency electromagnetic field (30 and
      50 Hz) immediately before or after the injection of morphine may be a potential
      method for treating the development of morphine tolerance in rats.
      Bioelectromagnetics. 38:618-625, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 29023860
TI  - Disentangling Effects of Input Frequency and Morphophonological Complexity on
      Children's Acquisition of Verb Inflection: An Elicited Production Study of
      Japanese.
AB  - This study aims to disentangle the often-confounded effects of input frequency
      and morphophonological complexity in the acquisition of inflection, by focusing
      on simple and complex verb forms in Japanese. Study 1 tested 28 children aged 3;3
      4;3 on stative (complex) and simple past forms, and Study 2 tested 30 children
      aged 3;5-5;3 on completive (complex) and simple past forms, with both studies
      using a production priming paradigm. Mixed effects models for children's
      responses were built to test the prediction that children's verb use is explained
      by the relative bias in input frequency between the two inflectional forms.
      Although Study 1 did not show a significant effect of input bias (apparently due
      to problems with item selection), Study 2, which corrected for this problem,
      yielded the predicted relationship. These findings suggest that input frequency
      effects, at the level of different inflectional forms of the same verb stem, hold
      even after controlling for morphophonological complexity.

PMID- 29023861
TI  - Analgesic, Antiinflammatory, and Antipyretic Effects of S(+)-Ketoprofen In Vivo.
AB  - Many studies indicate that the S-enantiomers of arylpropionic (APA) nonsteroidal
      antiinflammatory drugs (NSAIDs) are the pharmacologically active enantiomers.
      S(+)-ketoprofen (dexketoprofen) stereoselectively inhibits cyclooxygenase (COX)
      in vitro but very little is known about the differential activity of ketoprofen
      enantiomers in vivo. We examined the analgesic, antiinflammatory, and antipyretic
      activities of S(+)-ketoprofen in rats and mice. First, we measured the
      antinociceptive action of S(+)-ketoprofen in abdominal pain models. After
      intravenous administration, 0.5 mg/kg S(+)-ketoprofen inhibited 92.1 +/- 2.2% of
      writhing in mice. Stereoselectivity in the activity was detected; intravenous
      administration of the R(-)-enantiomer resulted in no statistically significant
      activity in a dose range of 0.15-1 mg/kg. Similar results were obtained after
      oral administration in mice. In the rat, S(+)-ketoprofen was a more potent
      analgesic than diclofenac by both intravenous and oral administration. There was
      no significant difference between the analgesic effect of S(+)-ketoprofen
      treatment and the twofold dose of the racemic form in both the mouse and rat
      models. Second, we measured the antiinflammatory activity of S(+)-ketoprofen
      using a carrageenan-induced paw edema model in the rat. Intravenous
      administration of 5 mg/kg of S(+)-ketoprofen almost completely inhibited edema
      formation. After oral administration, S(+)-ketoprofen is both more potent and
      effective than diclofenac. Third, we measured antipyretic activity. S(+)
      ketoprofen showed a marked antipyretic action (ED50 = 1.6 mg/kg) and was the most
      potent of the NSAIDs tested. S(+)-ketoprofen is a potent antiinflammatory,
      analgesic, and antipyretic agent in vivo, consistent with its potent anti-COX
      activity.

PMID- 29023862
TI  - Clinical Comparison of Dexketoprofen Trometamol, Ketoprofen, and Placebo in
      Dental Pain.
AB  - The efficacy and tolerability of single doses of dexketoprofen trometamol12.5 mg,
      25 mg, and 50 mg and ketoprofen 50 mg were compared in this double-blind,
      randomized, placebo-controlled study of 210 patients with moderate to severe pain
      after removal of one mandibular impacted third molar tooth. Pain intensity and
      pain relief were monitored for 6 h after administration of medication using
      visual analogue and verbal rating scales. All four active treatments were
      significantly more effective than placebo (P < 0.001). Dexketoprofen 25 mg and 50
      mg produced an analgesic effect within 30 min of administration and their effect
      persisted for 6 h. Ketoprofen 50 mg produced a level of analgesia similar to
      those of the higher doses of dexketoprofen trometamol, but it had a slower onset.
      The 12.5-mg dose of dexketoprofen trometamol was significantly superior to
      placebo but produced a lower level and shorter duration of analgesia compared to
      the other active treatments. There were no significant differences between 25 and
      50 mg of dexketoprofen trometamol in any measure of analgesic efficacy. No
      serious adverse events were observed and there were no significant differences in
      the incidence of adverse events among treatment groups. These results demonstrate
      that dexketoprofen trometamol 25 mg is at least as effective as the racemic
      ketoprofen 50 mg in the treatment of postsurgical dental pain. The more rapid
      onset of action compared to ketoprofen suggests that dexketoprofen trometamol is
      more appropriate for treatment of acute pain.

PMID- 29023863
TI  - The Effect of Food and an Antacid on the Bioavailability of Dexketoprofen
      Trometamol.
AB  - This randomized three-way, crossover pharmacokinetic study was performed to
      determine whether food or an antacid alters the bioavailability of dexketoprofen
      trometamol. A total of 24 healthy volunteers received three single 25 mg doses of
      dexketoprofen trometamol administered either in fasting condition, after an
      antacid (Maalox(r) ), or after a high-fat breakfast. Each volunteer received the
      three treatments in a randomized order, with a 7-day washout period between
      treatments. Blood samples were taken at regular intervals up to 24 h after dose.
      Plasma dexketoprofen concentrations were determined by HPLC and the main outcome
      measures were area under curve of concentration vs. time (AUC0-infinity ),
      maximal plasma concentration (Cmax .), and time to reach maximal concentration
      (tmax ). Administration of an antacid 10 min before dexketoprofen trometamol had
      no clinically relevant effect on any of the pharmacokinetic parameters. Food did
      not alter the extent of absorption of dexketoprofen trometamol, but tmax was
      significantly increased and Cmax significantly decreased compared with the
      fasting state. In conclusion, we can state that neither antacid nor food has a
      significant effect on the overall bioavailability of dexketoprofen trometamol.

PMID- 29023864
TI  - Comparison of Dexketoprofen Trometamol and Ketoprofen in the Treatment of
      Osteoarthritis of the Knee.
AB  - Dexketoprofen, the active enantiomer of the racemic compound ketoprofen, is a new
      nonsteroidal antiinflammatory drug (NSAID) of the arylpropionate family. The
      efficacy and safety of dexketoprofen trometamol were compared with the equivalent
      enantiomeric dose of ketoprofen in a multicenter, randomized, double-blind 3-week
      trial of adult outpatients with pain due to osteoarthritis of the knee. After a
      washout period of 7-15 days, patients were randomly assigned to receive either
      dexketoprofen trometamol 25 mg tid (N = 89) or ketoprofen 50 mg tid (N = 94). Of
      the 183 patients enrolled, two were lost to follow-up. At the end of treatment (3
      weeks), the main efficacy outcome measures were significantly better in the
      dexketoprofen trometamol group than in the ketoprofen group. In addition, overall
      physician assessment indicated that 75% of the dexketoprofen group had improved
      compared with 50% of the ketoprofen patients. There were fewer adverse events in
      the dexketoprofen treatment group, but the difference did not reach statistical
      significance. These results demonstrate that dexketoprofen trometamol 25 mg tid
      is more effective than ketoprofen 50 mg tid in short-term symptomatic treatment
      of knee osteoarthritis and suggest that the tolerability of dexketoprofen
      trometamol is more favorable than ketoprofen. Therefore, the substitution of
      dexketoprofen for racemic ketoprofen may be advantageous in clinical practice.

PMID- 29023865
TI  - Intestinal Ulcerogenic Effect of S(+)-Ketoprofen in the Rat.
AB  - Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit prostaglandin synthesis in
      the gastrointestinal mucosa, which can lead not only to stomach ulcers but also
      ulcers in the small and large intestines. Ulcers of the small intestine are less
      common than those of the stomach, but intestinal lesions are more life
      threatening. Although the R(-)-enantiomers of the arylpropionic acid (APA) class
      of NSAIDs are assumed to lack the toxic effects of cyclooxygenase inhibition,
      they may contribute to the ulcerogenicity of racemates. We have examined the
      intestinal ulcerogenic effects of single oral doses of S(+)-ketoprofen compared
      with racemic ketoprofen in the small intestine and cecum of rats. The toxicity in
      the small intestine was measured as the weight ratio between portions of
      intestine showing lesions and the total weight of the tissue. Toxicity in the
      cecum was evaluated by measuring the size of the ulcers. S(+)-ketoprofen had no
      significant ulcerogenic effect at 10 or 20 mg/kg. However, racemic ketoprofen was
      clearly ulcerogenic in the small intestine and cecum at the 40 mg dose. R(-)
      ketoprofen at 20 mg/kg does not show any effect in the cecum and only limited
      ulcerogenesis in the small intestine: The latter effect may be the result of
      racemic inversion. Therefore, the ulcerogenic action of racemic ketoprofen can be
      interpreted as a synergism between S(+)- and R(-)-ketoprofen. The mechanism of
      this synergism is not well understood but may be a general feature of APA NSAIDs.

PMID- 29023866
TI  - Antinociceptive Effects of S(+)-Ketoprofen and Other Analgesic Drugs in a Rat
      Model of Pain Induced Uric Acid.
AB  - We investigated the antinociceptive properties of dexketoprofen trometamol (S(+)
      ketoprofen tromethamine salt; SKP), a new analgesic, antiinflammatory drug, using
      the pain-induced functional impairment model in the rat (PIFIR), an animal model
      of arthritic pain. SKP was compared with racemic ketoprofen tromethamine salt
      (rac-KP), R(-)-ketoprofen tromethamine salt (RKP), ketorolac (KET), and morphine
      (MOR). We also assessed the effects of flurbiprofen (rac-FB) and its enantiomers
      (SFB and RFB) in the same model. Groups of six rats received either vehicle or
      analgesic drug and antinociception was evaluated by evaluating the dose-response
      curves over time. SKP was an effective antinociceptive drug in this model and was
      almost equally potent by either oral or intracerebroventricular administration.
      The oral potency of SKP was similar to that of oral KET and greater than that of
      oral MOR. No significant differences were observed between racemic ketoprofen and
      its enantiomers when administered orally. In the rat, significant bioinversion of
      RKP to SKP occurs when RKP is given orally. After oral administration of RKP, SKP
      was detectable in 30 min and surpassed the concentration of RKP after 3 h.
      Nevertheless, when the compounds were given intracerebroventricularly, some
      stereoselectivity in favor of SKP was observed. Stereoselectivity was observed
      with flurbiprofen, an analogue of ketoprofen that does not undergo significant
      metabolic inversion. Whereas SFB was an effective antinociceptive, RFB had no
      antinociceptive effect at the doses tested when given either orally or
      intracerebroventricularly.

PMID- 29023868
TI  - Dexketoprofen Trometamol.

PMID- 29023867
TI  - Bioavailability of S(+)-Ketoprofen After Oral Administration of Different
      Mixtures of Ketoprofen Enantiomers to Dogs.
AB  - Recent reports have disagreed on whether the bioavailability of S(+)-ketoprofen
      is affected by the presence of R(-)-ketoprofen. To examine this directly, we
      designed a randomized crossover study in beagle dogs. [14 C]- S(+)-ketoprofen
      trometamol and R(-)-ketoprofen trometamol were administered in the following
      percentage ratios: A, 99:1; B, 95:5; C, 90:10; D, 70:30; E, 50:50. Treatments
      were administered as a single oral dose of 1 mg/kg trometamol salt. Each of eight
      dogs received all five combinations in random order with a 1-week washout period
      between doses. Blood samples were taken before drug administration and at regular
      intervals for 240 min after dosing. A progressive increase in the plasma
      concentration of [14 C]-S(+)-ketoprofen was observed on going from treatment E
      (lowest dose of S-enantiomer) to treatments containing the highest doses of (14
      C]-S(+)-ketoprofen. When the pharmacokinetic calculations were normalized to the
      dose of (14 C]-S(+)-ketoprofen, we found no statistically significant differences
      among the normalized AUC and Cmax values of the five treatments. Therefore, S(+)
      ketoprofen absorption was linear and was not influenced by the presence of R(-)
      ketoprofen. Furthermore, there were no significant differences in tmax values
      among treatments, indicating that the rate of S(+)-ketoprofen absorption was also
      unaffected by the presence of R(-)-ketoprofen.

PMID- 29023869
TI  - Pharmacokinetics of Dexketoprofen Trometamol in Healthy Volunteers After Single
      and Repeated Oral Doses.
AB  - The pharmacokinetics of dexketoprofen trometamol were evaluated in two studies
      using healthy volunteers. In the first study, the relative bioavailability of a
      single oral capsule of dexketoprofen free acid 25 mg or dexketoprofen trometamol
      25 mg (given as 37 mg of the trometamol salt) was compared to ketoprofen 50 mg in
      18 healthy volunteers. In the second study, the pharmacokinetics and tolerability
      of oral dexketoprofen trometamol in tablet form were evaluated after either a
      single 25 mg dose (24 volunteers) or a repeated dose of 25 mg twice daily for 7
      days (12 volunteers). The absorption of dexketoprofen from dexketoprofen
      trometamol capsules was bioequivalent to that of ketoprofen. On the other hand,
      the extent of absorption of dexketoprofen free acid was significantly lower than
      that for ketoprofen. Dexketoprofen trometamol showed the most rapid absorption
      rate, with highest Cmax and shortest tmax values, whereas dexketoprofen free acid
      had the slowest absorption rate, and ketoprofen had an intermediate absorption
      rate. After repeated-dose administration of dexketoprofen trometamol, the
      pharmacokinetic parameters were similar to those obtained after single doses,
      indicating that no drug accumulation occurred. Dexketoprofen trometamol was well
      tolerated, with no clinically relevant adverse events reported.

PMID- 29023870
TI  - Clinical Comparison of Dexketoprofen Trometamol and Dipyrone in Postoperative
      Dental Pain.
AB  - A total of 125 outpatients with moderate to severe pain after surgical removal of
      one impacted third molar were randomly assigned to receive dexketoprofen
      trometamol 12.5 or 25 mg or dipyrone 575 mg. For first-dose assessments, patients
      rated their pain intensity and its relief at regular intervals. From 60 min post
      dose to the end of the 6-h observation period, both doses of dexketoprofen
      trometamol had higher pain relief scores than dipyrone: Between 3 and 6 h the
      differences were statistically significant. In addition, peak measures (PIDmax
      and PARmax ) were statistically superior after both doses of dexketoprofen
      trometamol compared to dipyrone. The overall efficacy assessed at the end of the
      first-dose phase was rated as good or excellent by 90%, 83.3%, and 70% of
      patients receiving dexketoprofen trometamol 25 mg, dexketoprofen trometamol 12.5
      mg, and dipyrone, respectively. The number of patients who required remedication
      during the 6-h period was significantly lower in both dexketoprofen groups.
      Repeated-dose data were also obtained. No significant differences were found in
      the efficacy after repeated doses, the number of doses taken, or the mean time
      elapsed between doses. The overall efficacy at the end of the repeated-dose phase
      was rated as good or excellent by 84.2%, 66.7%, and 70% of patients receiving
      dexketoprofen trometamol 25 mg, dexketoprofen trometamol 12.5 mg, and dipyrone,
      respectively. The frequency of adverse events was similar for all treatments and
      no serious adverse events were reported during the study.

PMID- 29023871
TI  - Comparison of the Efficacy and Tolerability of Dexketoprofen and Ketoprofen in
      the Treatment of Primary Dysmenorrhea.
AB  - Dexketoprofen, the pure S(+)-enantiomer of ketoprofen, is a promising new
      analgesic, but few clinical trials have yet examined its efficacy and
      tolerability. In this study, patients with a history of primary dysmenorrhea were
      treated with dexketoprofen doses of 12.5 and 25 mg, ketoprofen 50 mg, and placebo
      using a randomized, four-way crossover design. Efficacy analyses showed that
      dexketoprofen 12.5 and 25 mg and racemic ketoprofen 50 mg significantly reduced
      pain intensity compared with placebo from 1 h after dose to 4-6 h after dose.
      Interestingly, dexketoprofen at 12.5 mg was significantly superior to placebo at
      30 min after dose. Mean pain relief scores also demonstrated that both doses of
      dexketoprofen and racemic ketoprofen were significantly superior to placebo at 1
      6 h after the first dose. No indices of analgesic efficacy showed any significant
      differences between the two doses of dexketoprofen or between dexketoprofen and
      ketoprofen. After repeated dose administration, similar results were obtained.
      There were no significant effects of any treatment on activities of daily living,
      menstrual flow, or associated symptoms. Dexketoprofen was effective, well
      tolerated, and had no difference in the incidence of adverse events compared to
      ketoprofen or placebo.

PMID- 29023873
TI  - Juvenile elastoma without germline mutations in LEMD3 gene: A case of Buschke
      Ollendorff syndrome?
AB  - We report the case of a 6-year-old Caucasian girl with clinical and
      histopathologic features of Buschke-Ollendorff syndrome. Histologic examination
      of skin lesions showed thick, curly, elastic fibers in the derma. Bone lesions
      compatible with Buschke-Ollendorff syndrome were found in the girl's mother.
      Mutations in LEMD3 are pathogenic for Buschke-Ollendorff syndrome. Analysis of
      all exons and exon-intron junctions of LEMD3 did not reveal any germline
      mutations.

PMID- 29023872
TI  - Cell death markers in patients with cirrhosis and acute decompensation.
AB  - : The aims of this study were to determine the role of cell death in patients
      with cirrhosis and acute decompensation (AD) and acute on chronic liver failure
      (ACLF) using plasma-based biomarkers. The patients studied were part of the
      CANONIC (CLIF Acute-on-Chronic Liver Failure in Cirrhosis) study (N = 337; AD,
      258; ACLF, 79); additional cohorts included healthy volunteers, stable patients
      with cirrhosis, and a group of 16 AD patients for histological studies. Caspase
      cleaved keratin 18 (cK18) and keratin 18 (K18), which reflect apoptotic and total
      cell death, respectively, and cK18:K18 ratio (apoptotic index) were measured in
      plasma by enzyme-linked immunosorbent assay. The concentrations of cK18 and K18
      increased and the cK18:K18 ratio decreased with increasing severity of AD and
      ACLF (P < 0.001, respectively). Alcohol etiology, no previous decompensation, and
      alcohol abuse were associated with increased cell death markers whereas
      underlying infection was not. Close correlation was observed between the cell
      death markers and, markers of systemic inflammation, hepatic failure, alanine
      aminotransferase, and bilirubin, but not with markers of extrahepatic organ
      injury. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining
      confirmed evidence of greater hepatic cell death in patients with ACLF as opposed
      to AD. Inclusion of cK18 and K18 improved the performance of the CLIF-C AD score
      in prediction of progression from AD to ACLF (P < 0.05). CONCLUSION: Cell death,
      likely hepatic, is an important feature of AD and ACLF and its magnitude
      correlates with clinical severity. Nonapoptotic forms of cell death predominate
      with increasing severity of AD and ACLF. The data suggests that ACLF is a
      heterogeneous entity and shows that the importance of cell death in its
      pathophysiology is dependent on predisposing factors, precipitating illness,
      response to injury, and type of organ failure. (Hepatology 2018;67:989-1002).

PMID- 29023874
TI  - Multidisciplinary studies of wildlife trade in primates: Challenges and
      priorities.
AB  - Wildlife trade is increasingly recognized as an unsustainable threat to primate
      populations and informing its management is a growing focus and application of
      primatological research. However, management policies based on ecological
      research alone cannot address complex socioeconomic or cultural contexts as
      drivers of wildlife trade. Multidisciplinary research is required to understand
      trade complexity and identify sustainable management strategies. Here, we define
      multidisciplinary research as research that combines more than one academic
      discipline, and highlight how the articles in this issue combine methods and
      approaches to fill key gaps and offer a more comprehensive understanding of
      underlying drivers of wildlife trade including consumer demand, enforcement
      patterns, source population status, and accessibility of targeted species. These
      articles also focus on how these drivers interact at different scales, how trade
      patterns relate to ethics, and the potential effectiveness of different policy
      interventions in reducing wildlife trade. We propose priorities for future
      research on primate trade including expanding from multidisciplinary to
      interdisciplinary research questions and approaches co-created by research teams
      that integrate across different disciplines such as cultural anthropology,
      ecology, economics, and public policy. We also discuss challenges that limit the
      integration of information across disciplines to meet these priorities.

PMID- 29023875
TI  - Optimal endpoint for catheter ablation of longstanding persistent atrial
      fibrillation: A randomized clinical trial.
AB  - BACKGROUND: In longstanding persistent atrial fibrillation (LPeAF), the ideal
      endpoint of ablation remains to be determined. This study was to explore the
      value of pursuing AF termination or no with the same strategy during ablation on
      the long-term outcomes in patients with LPeAF. METHODS: Utilized "CCL" strategy
      is a fixed ablation approach consisting of circumferential pulmonary vein antrum
      isolation, ablation of complex fractionated atrial electrogram, and linear
      ablation between two anatomical structures (the mitral isthmus, left atrial
      roof). Note that 400 patients were randomized to group A (technical endpoint) and
      group B (pursuing AF termination). RESULTS: A group with technical endpoint had
      lower rate of acute AF termination (AF->sinus rhythm, 3.5% vs 18.1%; AF->atrial
      tachycardia, 23.7% vs 44.7%; P < 0.01) and shorter duration of ablation (164.9 +/
      20.8 vs 223.4 +/- 24.9, P < 0.01), radiofrequency delivery time (69.8 +/- 18.1
      vs 102.2 +/- 26.3, P < 0.01), and x-ray exposure time (18.2 +/- 8.8 vs 27.9 +/-
      12.4, P < 0.01) than those in B group (pursuing AF termination). During follow
      up, freedom from atrial arrhythmias did not differ between the two groups after a
      single ablation procedure (46.5% vs 54.3%, P=0.12) and the final ablation
      procedure (60.1% vs 65.8%, P  =  0.24). CONCLUSION: In patients of LPeAF,
      pursuing AF termination during ablation was associated with similar long-term
      clinical outcome compared to that with technical endpoint. Ablation to
      termination is not the best strategy during ablation.

PMID- 29023876
TI  - MRI assessment of treatment delivery for interstitial photodynamic therapy of
      high-grade glioma in a preclinical model.
AB  - BACKGROUND: High-grade gliomas are primary brain tumors that have shown
      increasing incidence and unfavorable outcomes. Local control is crucial to the
      management of this pathology. Photodynamic therapy (PDT), based on the light
      induced activation of a photosensitizer (PS), achieves local treatment by
      inducing selective lesions in tumor tissue. OBJECTIVES: Previous studies have
      reported the outcomes of PDT for glioblastoma via immunohistological data. Our
      study aimed to evaluate MRI findings, including diffusion, and perfusion
      sequences, compared with immunohistological data from the same population to
      address the efficiency of light fractionation. MATERIALS AND METHODS: Twenty-six
      "nude" rats grafted with human U87 cells into the right putamen underwent PDT.
      After PS precursor (5-ALA) intake, an optical fiber was introduced into the
      tumor. The rats were randomized into the following groups: those without
      illumination and those that received two or five fractions of light. Treatment
      effects were assessed with early high-field MRI to measure the volume of necrosis
      and edema using diffusion and perfusion sequences; the MRI results were compared
      with immunohistology results, including necrosis and apoptosis markers. RESULTS:
      Elevated diffusion values were observed on MRI in the centers of the tumors of
      the treated animals, especially in the 5-fraction group (P < 0.01). Perfusion was
      decreased around the treatment site, especially in the 5-fraction group (P =
      0.024). The MRI findings were consistent with previously published histological
      data. The median volume of necrosis was significantly different between the sham
      group and treated groups, 0 mm3 versus 2.67 mm3 , P < 0.001. The same trend was
      previously observed in histology data when grading the absence or presence of
      necrosis and when the presence of necrosis was significantly more predominant for
      the treated group than for the untreated group (P < 001). Additionally, cell
      death represented by apoptosis marker data (TUNEL method) was significantly
      higher in the 5-fraction group than in the 2-fraction group (P = 0.01).
      CONCLUSION: Diffusion and perfusion MRI revealed histological lesions.
      Interstitial PDT (iPDT) induced specific lesions in the tumor tissue, which were
      observed with MRI and confirmed by histopathological analysis. Thus, MRI may
      provide a non-invasive and reliable tool to assess treatment outcomes after PDT.
      Lasers Surg. Med. 50:460-468, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29023877
TI  - Letter: older age and male gender increase the risk of hepatocellular carcinoma
      after hepatitis B surface antigen (HBsAg) seroclearance.

PMID- 29023878
TI  - Letter: low rates of HBV serology testing in patients with chronic hepatitis C
      receiving direct acting antivirals.

PMID- 29023879
TI  - Editorial: a novel approach to monitor mucosal healing in coeliac disease-as
      simple as shifting goalposts?

PMID- 29023880
TI  - Letter: low rates of HBV serology testing in patients with chronic hepatitis C
      receiving direct acting antivirals - Authors' reply.

PMID- 29023881
TI  - Review article: the role of the microcirculation in liver cirrhosis.
AB  - BACKGROUND: Intrahepatic microvascular derangements and microcirculatory
      dysfunction are key in the development of liver cirrhosis and its associated
      complications. While much has been documented relating to cirrhosis and the
      dysfunction of the microcirculation in the liver parenchyma, far less is known
      about the state of the extrahepatic microcirculation and the role this may have
      in the pathogenesis of multiple organ failure in end stage liver cirrhosis. AIM:
      To provide an update on the role of the microcirculation in the pathophysiology
      of cirrhosis and its associated complications and briefly discuss some of the
      imaging techniques which may be used to directly investigate the
      microcirculation. METHODS: A Medline literature search was conducted using the
      following search terms: 'cirrhosis', 'microcirculation', 'circulation',
      'systemic', 'inflammation', 'peripheral', 'hepatorenal' and 'hepatopulmonary'.
      RESULTS: Significant heterogeneous microvascular alterations exist in patients
      with cirrhosis. Data suggest that the systemic inflammation, associated with
      advanced cirrhosis, induces microcirculatory dysregulation and contributes to
      haemodynamic derangement. The resultant vasoconstriction and hypoperfusion in the
      systemic extrahepatic microvasculature, is likely to be instrumental in the
      pathophysiology of organ failure in decompensated cirrhosis, however the
      mechanistic action of vasoactive agents used to correct the circulatory
      disturbance of advanced cirrhosis is poorly understood. CONCLUSIONS: Further
      research into the role of the microcirculation in patients with liver cirrhosis,
      will improve physicians understanding of the pathophysiology of cirrhosis, and
      may provide a platform for real time evaluation of an individual's
      microcirculatory response to vasoactive mediators, thus guiding their therapy.

PMID- 29023882
TI  - Editorial: a novel approach to monitor mucosal healing in coeliac disease-as
      simple as shifting goalposts? Authors' reply.

PMID- 29023883
TI  - Editorial: the role of statins in the treatment of alcohol-related cirrhosis -
      Authors' reply.

PMID- 29023884
TI  - Editorial: do thiopurines and biologics decrease the risk of colectomy?

PMID- 29023885
TI  - Letter: immunogenicity of infliximab originator vs. CT-P13 in IBD patients
      authors' reply.

PMID- 29023886
TI  - Editorial: optimising non-invasive screening for advanced liver fibrosis in
      NAFLD.

PMID- 29023887
TI  - Letter: the outcome of ulcerative colitis patients undergoing pouch surgery may
      be determined by pre-surgical factors. Authors' reply.

PMID- 29023888
TI  - Editorial: do thiopurines and biologics decrease the risk of colectomy? Authors'
      reply.

PMID- 29023889
TI  - Letter: immunogenicity of infliximab originator vs. CT-P13 in IBD patients.

PMID- 29023890
TI  - Letter: the outcome of ulcerative colitis patients undergoing pouch surgery may
      be determined by pre-surgical factors.

PMID- 29023891
TI  - Editorial: the role of statins in the treatment of alcohol-related cirrhosis.

PMID- 29023892
TI  - Labelling with positron emitters of pnicogens and chalcogens.
AB  - The increasing importance of the positron emission tomography (PET) in clinical
      diagnosis led to the development of a multitude of radiotracers labelled with
      positron-emitting radionuclides of groups 15 (pnicogens) and 16 (chalcogens) of
      the periodic table of elements. The positron emitters of the endogenous occurring
      elements nitrogen, phosphorus, oxygen, and sulphur are characterized by very
      short half-lives compared with the most commonly used PET radionuclides carbon-11
      or fluorine-18. Therefore, the potential of their synthesis and possible
      applications in PET is challenging and limited. On the other hand, the
      nonstandard positron emitters arsenic-72, arsenic-74, and selenium-73 have half
      lives in the range of hours to days and, thus, are of interest for PET studies of
      processes with long biological half-lives, but novel methods have to be developed
      for their application, especially in the no-carrier-added state. This review
      summarizes recent research concerning the positron emitters of pnicogens and
      chalcogens for radiolabelling applications.

PMID- 29023893
TI  - Analysis of renal blood flow and renal volume in normal fetuses and in fetuses
      with a solitary functioning kidney.
AB  - OBJECTIVE: To evaluate renal blood flow and renal volume for the prediction of
      postnatal renal function in fetuses with solitary functioning kidney (SFK).
      METHODS: Seventy-four SFK fetuses (unilateral renal agenesis [12], multicystic
      dysplastic kidney [36], and severe renal dysplasia [26]) were compared with 58
      healthy fetuses. Peak systolic velocity (PSV), pulsatility index (PI), and
      resistance index (RI) of the renal artery (RA) were measured; 2D and 3D (VOCAL)
      volumes were calculated. Renal length and glomerular filtration rate (GFR) were
      obtained in SFK children (2 years). RESULTS: Compared with the control group, the
      PSV RA was significantly lower in nonfunctioning kidneys and significantly higher
      in SFK. Volume measurements indicated a significantly larger volume of SFK
      compared with healthy kidneys. All but 4 children had GFR above 70 mL/min/1.73 m2
      , and compensatory hypertrophy was present in 69% at 2 years. PSV RA and SFK
      volume correlated with postnatal renal hypertrophy. No correlation between
      prenatal and postnatal SFK volume and GFR at 2 years was demonstrated.
      CONCLUSION: Low PSV RA might have a predictive value for diagnosing a
      nonfunctioning kidney in fetuses with a SFK. We demonstrated a higher PSV RA and
      larger renal volume in the SFK compared with healthy kidneys.

PMID- 29023894
TI  - Perineal groove in female infants: A case series and literature review.
AB  - BACKGROUND: Perineal groove is a rare congenital malformation that is unknown to
      many clinicians and is often misdiagnosed. Although it may be self-resolving
      during childhood, this nonepithelized mucous membrane can pose the risk of local
      irritation and infection, particularly urinary tract infection. METHODS: A
      retrospective study of female infants diagnosed with a perineal groove was
      performed, demographic characteristics and clinical features were analyzed, and a
      photographic review was conducted. RESULTS: Five patients with perineal groove
      were observed in our clinic in 2015-16. The mean age was 14 months. None had
      symptoms, and no treatment was required. During follow-up of 1 year, all remained
      asymptomatic. CONCLUSIONS: Our retrospective review suggests that perineal groove
      may be an underdiagnosed condition. Most cases resolve spontaneously, but
      confusion in diagnosis may lead to misdiagnosis or misinterpretation of sexual
      abuse and unnecessary treatments.

PMID- 29023895
TI  - Extracellular vesicles as novel therapeutics in hepatic failure.

PMID- 29023896
TI  - Predicting changes in hemoglobin S after simple transfusion using complete blood
      counts.
AB  - BACKGROUND: Hemoglobin S percentages are used in the management of patients who
      have sickle cell disease. However, hemoglobin S measurements often are not
      routinely or rapidly performed. Rapid and accurate methods to estimate hemoglobin
      S levels after simple transfusion may improve the care of patients with sickle
      cell disease. STUDY DESIGN AND METHODS: A comprehensive review of the electronic
      medical record identified 24 stable patients with sickle cell disease who
      received simple red blood cell transfusions and had hemoglobin S measurements
      before and after the transfusion that were less than 72 hours apart. Examination
      of these patients identified 62 separate transfusions that met our criteria.
      Three simple equations that utilized complete blood count values and readily
      available information from the medical record were used to predict the post
      transfusion hemoglobin S level after transfusion (Equation 1: predicted post
      transfusion hemoglobin = pre-transfusion hemoglobin S * [pre-transfusion
      hemoglobin/post-transfusion hemoglobin]; Equation 2: predicted post-transfusion
      hemoglobin S = pre-transfusion hemoglobin S * [pre-transfusion hematocrit/post
      transfusion hematocrit]; and Equation 3: predicted post-transfusion hemoglobin S
      = pre-transfusion hemoglobin S * total pre-transfusion hemoglobin/[total pre
      transfusion hemoglobin + (red blood cell volume * 20)]). RESULTS: The predicted
      hemoglobin S values for all three equations showed a highly significant
      correlation with the measured post-hemoglobin S value. The coefficient of
      determination (R2 ) for Equations 1, 2, and 3 was 0.95, 0.92, and 0.97,
      respectively. Predicting the post-transfusion hemoglobin S value using estimates
      of the patient's total hemoglobin and the transfused hemoglobin (Equation 3) was
      the most precise. CONCLUSION: Reductions in hemoglobin S values in patients with
      sickle cell disease who receive simple red blood cell transfusions can be
      reliably predicted using complete blood cell measurements and simple arithmetic
      equations.

PMID- 29023897
TI  - ATF1 and RAS in exosomes are potential clinical diagnostic markers for cervical
      cancer.
AB  - Cervical cancer is one of the most common cancers among women worldwide. It is
      highly lethal yet can be treated when found in early stage. Thus, early detection
      is of significant important for early diagnosis of cervical cancer. Exosomes have
      been used as biomarkers in clinical diagnosis. It is unknown that whether blood
      exosomes associated with cervical cancer can be detected and if these exosomes
      can accurately represent the developmental stage of cervical cancer. Mouse models
      were made out of a relapsed cervical cancer patient's tumour sample for original
      and recurrent cervical cancer, and gene analysis in both tumours and exosomes in
      these mouse models were performed. We found that activating transcription factor
      1 (ATF1) and RAS genes were significantly up-regulated in tumours of both primary
      and recurrent cervical cancer mouse model, and they can also be detected in the
      blood exosomes of the mouse model. Our results indicated that ATF1 and RAS could
      be potential candidate biomarkers for cervical cancer in early diagnosis. ATF1
      and RAS genes were found significantly elevated in tumours of primary and
      recurrent cervical cancer mouse model, and they were also detected in the blood
      exosomes. Therefore, ATF1 and RAS could be used as a diagnostic marker for
      cervical cancer in the future.

PMID- 29023898
TI  - Impact of Ketamine Use on Adjunctive Analgesic and Sedative Medications in
      Critically Ill Trauma Patients.
AB  - BACKGROUND: Ketamine may be used to manage pain and agitation that is refractory
      to what are usually considered traditional agents such as fentanyl, propofol,
      benzodiazepines, and dexmedetomidine; however, literature describing the use of
      ketamine continuous infusions for this purpose in critically ill trauma patients
      is limited. OBJECTIVES: The primary objective of this study was to determine the
      impact of the initiation of a ketamine continuous infusion on sedative and
      analgesic use in critically ill trauma patients. Secondary objectives were to
      identify the patient population in which ketamine was initiated, assess the
      proportion of time patients were at their goal level of sedation, and determine
      the dosing patterns of adjunctive sedative agents. METHODS: This single-center
      retrospective chart review over a 19-month period included critically ill
      mechanically ventilated adult trauma patients in whom a ketamine continuous
      infusion was initiated for management of sedation and agitation. Patients who
      received ketamine for other indications or by the acute pain management service
      were not included in this evaluation. RESULTS: Thirty-six patients were included
      in the study. Patients in whom ketamine was initiated tended to be white men with
      blunt trauma. Overall, the initiation of ketamine was associated with a decrease
      in the amount of opioids and propofol used and an increase in the amount of
      ziprasidone and dexmedetomidine needed to achieve the goal Richmond Agitation
      Sedation Score. When compared with the time period before ketamine initiation,
      the proportion of time that patients achieved goal sedation was not significantly
      different after the addition of ketamine. CONCLUSIONS: Although the use of
      ketamine in critically ill mechanically ventilated adult trauma patients was
      associated with decreased opioid use, it was also associated with increased use
      of dexmedetomidine and ziprasidone to achieve and maintain sedation. Further
      examination of clinical outcomes associated with these differences in drug use in
      a larger population of trauma patients is warranted before routine use of
      ketamine for analgesia and sedation can be recommended.

PMID- 29023899
TI  - Visceral adiposity increases risk for hepatocellular carcinoma in male patients
      with cirrhosis and recurrence after liver transplant.
AB  - : Visceral adipose tissue (VAT) is a metabolically active organ, associated with
      higher risk of malignancies. We evaluated whether VAT is associated with the risk
      of hepatocellular carcinoma (HCC) in patients presenting with cirrhosis as well
      as HCC recurrence after liver transplantation (LT). Patients with cirrhosis (n =
      678; 457 male) who were assessed for LT (289 with HCC) were evaluated for body
      composition analysis. Patients who underwent LT (n = 247, 168 male) were
      subsequently evaluated for body composition, and 96 of these patients (78 male)
      had HCC. VAT, subcutaneous adipose tissues, and total adipose tissues were
      quantified by computed tomography at the level of the third lumbar vertebra and
      reported as indexes (cross-sectional area normalized for height [square
      centimeters per square meter]). At the time of LT assessment, the VAT index
      (VATI) was higher in male patients with HCC compared to non-HCC patients (75 +/-
      3 versus 60 +/- 3 cm2 /m2 , P = 0.001). The VATI, subcutaneous adipose tissue
      index, and total adipose tissue index were higher in male patients with HCC
      compared to non-HCC patients. By multivariate analysis, male patients with VATI
      >=65 cm2 /m2 had a higher risk of HCC (hazard ratio, 1.90; 95% confidence
      interval, 1.31-2.76; P = 0.001). In male patients with HCC who underwent LT, a
      VATI >=65 cm2 /m2 adjusted for Milan criteria was independently associated with
      higher risk of HCC recurrence (hazard ratio, 5.34; 95% confidence interval, 1.19
      23.97; P = 0.03). CONCLUSION: High VATI is an independent risk factor for HCC in
      male patients with cirrhosis and for recurrence of HCC after LT. (Hepatology
      2018;67:914-923).

PMID- 29023900
TI  - Durability and flexibility of chimpanzee grooming patterns during a period of
      dominance instability.
AB  - Growing evidence from studies on primates and other taxa has shown that the
      maintenance of long-term affiliative patterns influences fitness. Thus,
      understanding how individuals regulate social interactions in response to
      environmental and social factors contributes to our understanding of the
      evolutionary basis of sociality. We investigated the durability of affiliation
      patterns in chimpanzees across three 3-month periods of varying social
      uncertainty depending on the degree of stability in the male hierarchy, with a 2
      year gap between each period. Periods were unstable (no clear alpha male),
      recently stable (new alpha male just established) and stable (alpha male in place
      for 2 years). We focused on three features of social exchange shared by human and
      non-human primates: consistency of exchanges across periods, durability of
      preferred partners, and degree of reciprocity in each period. We compared male-to
      male, female-to-female, male-to-female, and female-to-male grooming patterns.
      Overall, more grooming was exchanged in the stable period. Grooming patterns were
      not consistent across the three periods, but were only consistent between the
      recently stable and stable periods for female-to-female and male-to-female dyads.
      As predicted from the opportunistic nature of male relationships, male-to-male
      grooming was least likely to be correlated across all periods and males had
      relatively fewer durable (i.e., preferred partners in all periods) same-sex
      partners than females. Our predictions that grooming reciprocity would be less
      likely during the unstable period and in male-male dyads were only partially
      supported. We found grooming reciprocity in all periods for female-female dyads
      but only in the stable period for male-male and female-male dyads. Although long
      term affiliative patterns are well studied in primates, this is the first study
      to investigate the association between social uncertainty and durability of
      affiliative patterns. Our findings suggest social uncertainty influences social
      exchange and highlight the importance of considering group instability in studies
      of social relationships.

PMID- 29023901
TI  - Additive manufactured push-fit implant fixation with screw-strength pull out.
AB  - Additive manufacturing offers exciting new possibilities for improving long-term
      metallic implant fixation in bone through enabling open porous structures for
      bony ingrowth. The aim of this research was to investigate how the technology
      could also improve initial fixation, a precursor to successful long-term
      fixation. A new barbed fixation mechanism, relying on flexible struts was
      proposed and manufactured as a push-fit peg. The technology was optimized using a
      synthetic bone model and compared with conventional press-fit peg controls tested
      over a range of interference fits. Optimum designs, achieving maximum pull-out
      force, were subsequently tested in a cadaveric femoral condyle model. The barbed
      fixation surface provided more than double the pull-out force for less than a
      third of the insertion force compared to the best performing conventional press
      fit peg (p < 0.001). Indeed, it provided screw-strength pull out from a push-fit
      device (1,124 +/- 146 N). This step change in implant fixation potential offers
      new capabilities for low profile, minimally invasive implant design, while
      providing new options to simplify surgery, allowing for one-piece push-fit
      components with high levels of initial stability. (c) 2017 The Authors. Journal
      of Orthopaedic Research(r) Published by Wiley Periodicals, Inc. on behalf of the
      Orthopaedic Research Society. J Orthop Res 36:1508-1518, 2018.

PMID- 29023904
TI  - Terminating and episode of overt hepatic encephalopathy: L-ornithine-L-aspartate
      may have some role.

PMID- 29023902
TI  - An incidental finding of maternal multiple myeloma by non invasive prenatal
      testing.

PMID- 29023903
TI  - Asian Organization for Crohn's and Colitis and Asian Pacific Association of
      Gastroenterology consensus on tuberculosis infection in patients with
      inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part
      1: Risk assessment.
AB  - Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly
      popular in many Asian countries, the risk of developing active tuberculosis (TB)
      among anti-TNF users may raise serious health problems in this region. Thus, the
      Asian Organization for Crohn's and Colitis and the Asian Pacific Association of
      Gastroenterology have developed a set of consensus statements about risk
      assessment, detection, and prevention of latent TB infection and management of
      active TB infection in patients with inflammatory bowel disease (IBD) receiving
      anti-TNF treatment. Twenty-three consensus statements were initially drafted and
      then discussed by the committee members. The quality of evidence and the strength
      of recommendations were assessed by using the Grading of Recommendations
      Assessment, Development, and Evaluation methodology. Web-based consensus voting
      was performed by 211 IBD specialists from nine Asian countries concerning each
      statement. A consensus statement was accepted if at least 75% of the participants
      agreed. Part 1 of the statements comprised two parts: (i) risk of TB infection
      during anti-TNF therapy and (ii) screening for TB infection prior to commencing
      anti-TNF therapy. These consensus statements will help clinicians optimize
      patient outcomes by reducing the morbidity and mortality related to TB infections
      in patients with IBD receiving anti-TNF treatment.

PMID- 29023906
TI  - Influence of Risk Perception on Attitudes and Norms Regarding Electronic
      Cigarettes.
AB  - The use of electronic cigarettes has grown substantially over the last few years.
      Currently, about 4% of adults use electronic cigarettes, about 16% of high school
      students report use in the past 30 days, as do approximately 11-25% of college
      students. A hallmark of the reduction in tobacco use has been the shift in social
      norms concerning smoking in public. Such norms may also drive views on
      acceptability of public electronic cigarette use. While normative factors have
      been given attention, little substantive application of the literature on risk
      perception has been brought to bear. The overall aim of this study was to place a
      cognitive-affective measure of risk perception within a model that also includes
      social cues for e-cigarettes, addictiveness beliefs, and tobacco use to predict
      perceived social acceptability for public use of e-cigarettes. To do so, a cross
      sectional study using an online survey was conducted among a sample of
      undergraduate students at a Western university (n = 395). A structural equation
      model showed that the acceptability of public e-cigarette use was influenced by
      social cues, beliefs about addiction, and cognitive risk perception, even after
      controlling for nicotine use. What is revealed is that cognitive assessment of e
      cigarette risk and perception of addictiveness had a suppressing effect on
      perceived acceptability of public vaping, while greater exposure to social cues
      exerted a countervailing effect. This is evidence of the role that risk
      perception and social norms may play in the increases in electronic cigarette use
      that have been observed.

PMID- 29023905
TI  - Cholangiopathy in critically ill patients surviving beyond the intensive care
      period: a multicentre survey in liver units.
AB  - BACKGROUND: The outcome of cholangiopathy developing in intensive care unit (ICU)
      is not known in patients surviving their ICU stay. AIM: To perform a survey in
      liver units, in order to clarify the course of cholangiopathy after surviving ICU
      stay. METHODS: The files of the liver units affiliated to the French network for
      vascular liver disease were screened for cases of ICU cholangiopathy developing
      in patients with normal liver function tests on ICU admission, and no prior
      history of liver disease. RESULTS: Between 2005 and 2015, 16 cases were
      retrieved. Extensive burns were the cause for admission to ICU in 11 patients.
      Serum alkaline phosphatase levels increased from day 11 (2-46) to a peak of 15 (4
      32) * ULN on day 81 (12-511). Magnetic resonance cholangiography showed
      irregularities or frank stenosis of the intrahepatic ducts, and proximal
      extrahepatic ducts contrasting with a normal aspect of the distal common bile
      duct. Follow-up duration was 20.6 (4.7-71.8) months. Three patients were lost to
      follow-up; 2 patients died from liver failure and no patient was transplanted.
      One patient had worsening strictures of the intrahepatic bile ducts with
      jaundice. Nine patients had persistent but minor strictures of the intrahepatic
      bile ducts on MR cholangiography, and persistent cholestasis without jaundice.
      One patient had normal liver function tests. CONCLUSIONS: In patients surviving
      their ICU stay, ICU cholangiopathy is not uniformly fatal in the short term or
      clinically symptomatic in the medium term. Preservation of the distal common bile
      duct appears to be a finding differentiating ICU cholangiopathy from other
      diffuse cholangiopathies.

PMID- 29023908
TI  - Setting Priorities in Behavioral Interventions: An Application to Reducing
      Phishing Risk.
AB  - Phishing risk is a growing area of concern for corporations, governments, and
      individuals. Given the evidence that users vary widely in their vulnerability to
      phishing attacks, we demonstrate an approach for assessing the benefits and costs
      of interventions that target the most vulnerable users. Our approach uses Monte
      Carlo simulation to (1) identify which users were most vulnerable, in signal
      detection theory terms; (2) assess the proportion of system-level risk
      attributable to the most vulnerable users; (3) estimate the monetary benefit and
      cost of behavioral interventions targeting different vulnerability levels; and
      (4) evaluate the sensitivity of these results to whether the attacks involve
      random or spear phishing. Using parameter estimates from previous research, we
      find that the most vulnerable users were less cautious and less able to
      distinguish between phishing and legitimate emails (positive response bias and
      low sensitivity, in signal detection theory terms). They also accounted for a
      large share of phishing risk for both random and spear phishing attacks. Under
      these conditions, our analysis estimates much greater net benefit for behavioral
      interventions that target these vulnerable users. Within the range of the model's
      assumptions, there was generally net benefit even for the least vulnerable users.
      However, the differences in the return on investment for interventions with users
      with different degrees of vulnerability indicate the importance of measuring that
      performance, and letting it guide interventions. This study suggests that
      interventions to reduce response bias, rather than to increase sensitivity, have
      greater net benefit.

PMID- 29023907
TI  - Siblings' caring roles in families with a child with epilepsy.
AB  - Despite large amounts of care for chronic conditions being provided within the
      family, information regarding the extent to which siblings contribute to informal
      care practices in families where a child has a chronic condition is limited. This
      article draws on multiple perspective data from 24 families that had a child with
      epilepsy. In doing so, the article illustrates siblings' significant contribution
      to caring for their brother or sister and further develops the alert assistant
      concept. Two additional distinct caring roles that the siblings took on are also
      outlined - the substitute parent and parenting assistant roles. The relationship
      between siblings' socio-demographic characteristics and their caring
      responsibilities is also explored. The paper's findings are that siblings who
      were older, female and those in families with a higher child to parent ratio took
      on more caring responsibilities. Consequently, this article contributes to the
      currently limited literature on siblings who care for a chronically ill brother
      or sister by increasing understandings of different caring roles and experiences
      of chronic illness in families.

PMID- 29023909
TI  - Risks of Allergic Contact Dermatitis Elicited by Nickel, Chromium, and Organic
      Sensitizers: Quantitative Models Based on Clinical Patch Test Data.
AB  - Risks of allergic contact dermatitis (ACD) from consumer products intended for
      extended (nonpiercing) dermal contact are regulated by E.U. Directive EN 1811
      that limits released Ni to a weekly equivalent dermal load of <=0.5 MUg/cm2 .
      Similar approaches for thousands of known organic sensitizers are hampered by
      inability to quantify respective ACD-elicitation risk levels. To help address
      this gap, normalized values of cumulative risk for eliciting a positive (">=+")
      clinical patch test response reported in 12 studies for a total of n = 625 Ni
      sensitized patients were modeled in relation to observed ACD-eliciting Ni loads,
      yielding an approximate lognormal (LN) distribution with a geometric mean and
      standard deviation of GMNi = 15 MUg/cm2 and GSDNi = 8.0, respectively. Such data
      for five sensitizers (including formaldehyde and 2-hydroxyethyl methacrylate)
      were also ~LN distributed, but with a common GSD value equal to GSDNi and with
      heterogeneous sensitizer-specific GM values each defining a respective ACD
      eliciting potency GMNi /GM relative to Ni. Such potencies were also estimated for
      nine (meth)acrylates by applying this general LN ACD-elicitation risk model to
      respective sets of fewer data. ACD-elicitation risk patterns observed for Cr(VI)
      (n = 417) and Cr(III) (n = 78) were fit to mixed-LN models in which ~30% and ~40%
      of the most sensitive responders, respectively, were estimated to exhibit a LN
      response also governed by GSDNi . The observed common LN-response shape parameter
      GSDNi may reflect a common underlying ACD mechanism and suggests a common interim
      approach to quantitative ACD-elicitation risk assessment based on available
      clinical data.

PMID- 29023910
TI  - Is mIndy a mediator of energy metabolism reprogramming in hepatocellular
      carcinoma induced by interleukin-6/signal transducer and activator of
      transcription 3 signaling?

PMID- 29023911
TI  - Genomic diversity and population structure of Mexican and Spanish bovine Lidia
      breed.
AB  - The Lidia bovine breed is distinguished for its low genetic exchangeability given
      its selection on aggressive behavior, its management uniqueness and its
      subdivided structure. In this study, we present a comprehensive genome-wide
      analysis of genetic diversity, population structure and admixture of 468 animals
      from Mexican and Spanish Lidia breed populations and 64 samples belonging to 10
      Spanish native and American-creole breeds using 37 148 single nucleotide
      polymorphisms. We found similar average inbreeding values in the Lidia breed,
      with different distributions within groups; variability of inbreeding values
      among Spanish lineages was significant and no differences were found among the
      Mexican sub-populations. Together, the high FIS of the lineages and the behavior
      of the runs of homozygosity are consequences of the lineage's small effective
      population sizes, contributing to their inbreeding increase. Population admixture
      analysis discarded any influence on the genetic structure of the Lidia
      populations from the Spanish native and American-creole breeds. In addition, both
      Lidia populations depicted different genetic origins, with the exception of some
      Mexican individuals whose origins traced back to recent Spanish importations.

PMID- 29023913
TI  - Erratum.

PMID- 29023912
TI  - Basophils are recruited and localized at the site of tick bites in humans.

PMID- 29023914
TI  - Melanocytic naevi with perineurial differentiation: a distinctive variant of
      neurotised naevi and a diagnostic pitfall with desmoplastic melanoma.
AB  - AIMS: Spindle cell differentiation is not an uncommon finding in common acquired
      naevi, and may represent a form of neurotisation with Schwannian differentiation
      of melanocytes. Perineurial differentiation in this context appears to be very
      rare, and is only poorly documented in the literature. We therefore aimed to
      study this rare form of neurotisation in melanocytic naevi more comprehensively.
      METHODS AND RESULTS: We have identified six melanocytic tumours showing spindle
      cell morphology and perineurial differentiation from routine and referral
      material. Clinical data and follow-up were obtained, and the histological and
      immunohistochemical features were analysed. The tumours affected middle-aged
      adults (median, 48 years; range, 26-74 years), with a wide anatomical
      distribution and benign follow-up (median, 13 months; range, 6-48 months). All
      tumours were nodular and circumscribed but asymmetrical, with extension into the
      deep dermis and superficial subcutis. A characteristic finding was a biphasic
      growth pattern with a lentiginous compound naevus in the superficial aspect and
      abrupt transition to a prominent nodular spindle cell proliferation in the deeper
      reaches. Spindle cells were bland and uniform, and arranged singly and in short
      fascicles in a loose fibromyxoid stroma. In areas, a whorled arrangement of
      slender spindle cells with wavy nuclei was seen. Distinctive intratumoral
      hypocellular nodules and peripheral lymphoid aggregates were additional features.
      By immunohistochemistry, the spindle cells were mainly S100-positive melanocytes.
      In areas, S100-negative/epithelial membrane antigen-positive spindle cells
      showing coexpression of Glut-1 and claudin-1 were closely admixed. CONCLUSION:
      This perineurial differentiation probably represents a rare and unusual form of
      neurotisation. The tumours are benign but may be mistaken for desmoplastic
      melanoma. Awareness of and careful attention to the clinicopathological and
      immunohistochemical features allow reliable separation.

PMID- 29023916
TI  - Varicocele is associated with hypogonadism and impaired erectile function: A
      prospective comparative study.

PMID- 29023918
TI  - Scrutinizing the Genetic Underpinnings of Bone Strength.

PMID- 29023915
TI  - A randomized trial of obeticholic acid monotherapy in patients with primary
      biliary cholangitis.
AB  - : Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as
      monotherapy in an international, randomized, double-blind, placebo-controlled
      phase 2 study in patients with primary biliary cholangitis who were then followed
      for up to 6 years. The goals of the study were to assess the benefit of OCA in
      the absence of ursodeoxycholic acid, which is relevant for patients who are
      intolerant of ursodeoxycholic acid and at higher risk of disease progression.
      Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or
      OCA 50 mg (n = 16) given as monotherapy once daily for 3 months (1 randomized
      patient withdrew prior to dosing). The primary endpoint was the percent change in
      alkaline phosphatase from baseline to the end of the double-blind phase of the
      study. Secondary and exploratory endpoints included change from baseline to month
      3/early termination in markers of cholestasis, hepatocellular injury, and
      farnesoid X receptor activation. Efficacy and safety continue to be monitored
      through an ongoing 6-year open-label extension (N = 28). Alkaline phosphatase was
      reduced in both OCA groups (median% [Q1, Q3], OCA 10 mg -53.9% [-62.5, -29.3],
      OCA 50 mg -37.2% [-54.8, -24.6]) compared to placebo (-0.8% [-6.4, 8.7]; P <
      0.0001) at the end of the study, with similar reductions observed through 6 years
      of open-label extension treatment. OCA improved many secondary and exploratory
      endpoints (including gamma-glutamyl transpeptidase, alanine aminotransferase,
      conjugated bilirubin, and immunoglobulin M). Pruritus was the most common adverse
      event; 15% (OCA 10 mg) and 38% (OCA 50 mg) discontinued due to pruritus.
      CONCLUSION: OCA monotherapy significantly improved alkaline phosphatase and other
      biochemical markers predictive of improved long-term clinical outcomes. Pruritus
      increased dose-dependently with OCA treatment. Biochemical improvements were
      observed through 6 years of open-label extension treatment. (Hepatology
      2018;67:1890-1902).

PMID- 29023919
TI  - Causal narratives in public health: the difference between mechanisms of
      aetiology and mechanisms of prevention in non-communicable diseases.
AB  - Research in the health sciences has been highly successful in revealing the
      aetiologies of many morbidities, particularly those involving the microbiology of
      communicable disease. This success has helped form a narrative to be found in
      numerous public health documents, about interventions to reduce the burden of non
      communicable diseases (e.g., obesity or alcohol related pathologies). These focus
      on tackling the purported pathogenic factors causing the diseases as a means of
      prevention. In this paper, we argue that this approach has been sub-optimal. The
      mechanisms of aetiology and of prevention are sometimes significantly different
      and failure to make this distinction has hindered efforts at preventing non
      communicable diseases linked to diet, exercise and alcohol consumption. We
      propose a sociological approach as an alternative based on social practice
      theory. (A virtual abstract for this paper can be found at:
      https://www.youtube.com/channel/UC_979cmCmR9rLrKuD7z0ycA).

PMID- 29023920
TI  - The rise of the opioid epidemic and hepatitis C-positive organs: A new era in
      liver transplantation.
AB  - The use of hepatitis C virus (HCV)-positive organs in liver transplantation (LT)
      has increased in the era of direct-acting antiviral therapy. A rising demand for
      organs, the increased ability to effectively treat HCV infection in the
      transplant setting, and an unprecedented increase in HCV-positive donors have all
      contributed to this trend. A recent abrupt rise in opioid use in the United
      States has resulted in a surge of injection drug use, transmission of HCV, and
      opioid-related overdose deaths. Geographical areas most affected by the opioid
      epidemic have experienced a rapid increase in recovery and utilization of HCV
      positive donor organs, in which the proportion of deceased donor LTs in the
      United States from donors who are HCV positive has increased nearly 2-fold within
      the last 3 years. The prospect of expanding the organ donor pool with HCV
      positive donors and achieving acceptable posttransplant outcomes has generated
      much interest in the areas of liver, kidney, and thoracic transplantation,
      including the potential for transplanting organs from HCV positive donors into
      HCV-negative recipients. Developing strategies to ensure appropriate selection of
      potential recipients of HCV-positive organs, initiating timely antiviral therapy,
      and defining associated risks will be critical in achieving optimal
      posttransplant outcomes in this setting. (Hepatology 2018;67:1600-1608).

PMID- 29023921
TI  - Ecotoxicology: It's time for a hard re-look.

PMID- 29023917
TI  - Protein arginine methyl transferase 1- and Jumonji C domain-containing protein 6
      dependent arginine methylation regulate hepatocyte nuclear factor 4 alpha
      expression and hepatocyte proliferation in mice.
AB  - : Alcohol is a well-established risk factor for hepatocellular carcinoma (HCC),
      but the mechanisms by which it promotes liver cancer are not well understood.
      Several studies have shown that cellular protein arginine methylation is
      inhibited by alcohol. Arginine methylation is controlled by the reciprocal
      activity of protein arginine methyltransferases, primarily protein arginine
      methyl transferase 1 (PRMT1), and a demethylase Jumonji C domain-containing
      protein 6 (JMJD6). The aim of this study was to explore the role of arginine
      methylation changes in alcohol pathogenesis. We found that PRMT1 activity is
      inhibited in livers of mice fed with alcohol compared to pair-fed mice. Using
      hepatocyte-specific PRMT1 knockout mice, we identified that loss of PRMT1 results
      in enhanced hepatocyte proliferation and a 33% increase in liver size. This
      increased hepatocyte proliferation was associated with reduced expression of
      hepatocyte nuclear factor 4 alpha (Hnf4alpha), an important regulator of liver
      tumorigenesis. We found that PRMT1 regulates Hnf4alpha expression directly
      through arginine methylation at the (Hnf4alpha) promoter. In the absence of
      PRMT1, JMJD6 can demethylate the Hnf4alpha promoter and suppress its expression.
      We were able to restore Hnf4alpha expression and abolish the increase in
      hepatocyte proliferation by knockdown of JMJD6 in PRMT1 knockout mice. Knockdown
      of JMJD6 in alcohol-fed mice similarly increased Hnf4alpha expression. We then
      examined whether loss of arginine methylation might play a role in alcohol
      associated liver cancers. We examined 25 human HCC specimens and found a strong
      correlation (R = 0.8; P < 0.01) between arginine methylation levels and Hnf4alpha
      expression in these specimens, suggesting that the above mechanism is relevant in
      patients. CONCLUSION: Taken together, these data suggest that PRMT1 inhibition,
      such as induced by alcohol, may result in epigenetic changes leading to loss of
      Hnf4alpha. This effect may contribute to alcohol's ability to promote liver
      tumors. (Hepatology 2018;67:1109-1126).

PMID- 29023922
TI  - The efficacy of new antiviral regimens for hepatitis C infection: Evidence from a
      systematic review.

PMID- 29023923
TI  - Treatment abandonment in children with cancer in Sub-Saharan Africa: Systematic
      literature review and meta-analysis.
AB  - AIMS: To establish and quantify the main reasons for treatment abandonment in
      children with cancer in Sub-Saharan Africa through a systematic review of the
      literature. BACKGROUND: Great advances have been made in the treatment of
      childhood cancer, however this requires that families are able to complete
      treatment. Failure to do this is referred to as treatment abandonment, which is
      recognized as a reason for treatment failure. DESIGN: Systematic review and meta
      analysis of data on the reasons for treatment abandonment in Sub-Saharan Africa.
      DATA SOURCES: Ovid MEDLINE 1946 to May Week 1 2017 and Embase 1974 to 2017 Week
      19. Additional hand-searching was undertaken. REVIEW METHODS: Two reviewers
      independently screened papers and extracted the data. The R package meta was used
      to calculate the relative risk of treatment abandonment or the proportion of
      parents stating a reason. RESULTS: The relative risk of treatment abandonment was
      highest for not being in a research cohort; followed by mothers only having
      primary education, being HIV negative, parents not being employed, travel and no
      insurance. When parents who had abandoned treatment were asked, the most common
      reason was finance, followed by insurance, transport, lack of social support,
      their child appearing well, fear and waiting. CONCLUSIONS: More data are needed
      on the extent of treatment abandonment in different countries. Clinicians should
      encourage parents without insurance to enrol onto the relevant insurance
      programme straight after diagnosis, provide housing for patients and families
      close to the treatment centres and to develop treatment at more localized
      centres.

PMID- 29023924
TI  - A decreased peritumoral CD1a+ cell number predicts a worse prognosis in oral
      squamous cell carcinoma.
AB  - AIMS: Dendritic cells (DCs) are known to play a central role in the regulation of
      both innate and adaptive immunological responses, including antitumour immunity.
      The aim of this study was to evaluate the prognostic impact of intratumoral and
      peritumoral DCs in oral squamous cell carcinoma (OSCC) affecting the tongue and
      floor of the mouth. METHODS AND RESULTS: Immunohistochemistry for CD1a and CD83
      was performed in 53 patients with OSCC in the tongue and floor of the mouth. The
      markers were evaluated by automated examination in intratumoral and peritumoral
      compartments, and the results were expressed as density of cells/mm2 .
      Correlations between these data and clinicopathological and survival outcomes
      were investigated. Depletion of peritumoral CD1a+ cells was associated with lymph
      node metastasis (P = 0.05), whereas depletion of peritumoral CD83+ cells was
      correlated with smoking history (P = 0.04), lymph node metastasis (P = 0.015),
      and extracapsular spread of lymph nodes (P = 0.018). Peritumoral CD1a+ was
      correlated with recurrence (P = 0.007) and overall survival (P = 0.03). The
      results of the survival analysis with the Cox proportional hazard model showed
      that depletion of peritumoral CD1a+ cells is an independent factor associated
      with overall survival and disease-free survival. CONCLUSION: Our results suggest
      that depletion of peritumoral CD1a+ cells is a strong independent prognostic
      factor, predicting a higher recurrence rates and worse survival outcomes.

PMID- 29023925
TI  - Radioembolization for hepatocellular carcinoma: The time has come.

PMID- 29023926
TI  - Hyperthyroidism in patients with ischaemic heart disease after iodine load
      induced by coronary angiography: Long-term follow-up and influence of baseline
      thyroid functional status.
AB  - OBJECTIVE: To study the effect of a iodine load on thyroid function of patients
      with ischaemic heart disease (IHD) and the long-term influence of unknown
      subclinical hyperthyroidism. CONTEXT: Subclinical hyperthyroidism is considered
      an independent risk factors for cardiovascular morbidity of patients with IHD.
      They routinely undergo coronary angiography with iodine contrast media (ICM)
      which may induce or even worsen hyperthyroidism. DESIGN: A cross-sectional study
      followed by a longitudinal study on patients with subclinical hyperthyroidism.
      PATIENTS: 810 consecutive IHD outpatients without known thyroid diseases or
      treatment with drugs influencing thyroid activity undergoing elective coronary
      angiography. MEASUREMENTS: We evaluated thyroid function either before and 1
      month after ICM; patients with thyrotoxicosis at baseline or after ICM were then
      followed up for 1 year. RESULTS: 58 patients had hyperthyroidism at baseline (HB,
      7.2%), independently associated to FT4 levels, thyroid nodules and family history
      of thyroid diseases. After ICM, the prevalence of hyperthyroidism was 81 (10%).
      Hyperthyroidism after ICM was positively predicted by baseline fT4 levels,
      thyroid nodules, age over 60, male gender, family history of thyroid diseases.
      Three months after ICM, 34 patients (4.2%) still showed hyperthyroidism (22 from
      HB, 13 treated with methimazole). One year after ICM, hyperthyroidism was still
      present in 20 patients (2.5%, all from HB, 13 treated). CONCLUSIONS: The
      prevalence of spontaneous subclinical hyperthyroidism in IHD is surprisingly
      elevated and is further increased by iodine load, particularly in patients with
      thyroid nodules and familial history of thyroid diseases, persisting in a not
      negligible number of them even after one year.

PMID- 29023927
TI  - Interference of hepatitis B virus dual infection in platelet count recovery in
      chronic hepatitis C patients with curative antiviral therapy.
AB  - BACKGROUND AND AIM: Hepatitis C virus infection is associated with
      thrombocytopenia. Thrombocytopenia recovers after viral eradication. The current
      study explored the rate and factors associated with platelet (PLT) recovery,
      which may represent the degree of liver fibrosis regression. METHODS: A total of
      466 patients who achieved a sustained virological response were enrolled to
      compare the PLT change after a mean follow-up period of 85.5 months (range 12-163
      months). RESULTS: Platelet counts increased significantly after achieving
      sustained virological response (from 166 +/- 55 * 103 to 201 +/- 61 * 103  u/L, P
      < 0.001). The median PLT count increment was 5.03 * 103  u/L per year. Logistic
      regression analysis revealed that factors associated with slow PLT count recovery
      were high pretreatment PLT counts (odds ratio [OR]/ 95% confidence intervals
      [CI]: 0.992/0.989-0.996, P < 0.001) and hepatitis B virus (HBV) co-infection
      (OR/CI: 0.416/0.220-0.785, P = 0.007). High PLT counts were the only factor
      associated with slow PLT recovery in patients with mild liver disease (F0-2)
      (OR/CI: 0.992/0.987-0.996, P < 0.001). On the other hand, HBV co-infection was
      the only factor associated with slow PLT recovery in patients with advanced
      fibrosis (OR/CI: 0.207/0.054-0.789, P = 0.02). Linear regression analysis of
      factors correlated to the delta PLT count change per year in patients with F0-2
      included pretreatment white blood cell (beta: -0.001; CI: -0.002-0.000; P = 0.01)
      and pretreatment PLT counts (beta: -0.037; CI: -0.061 to -0.013; P = 0.003).
      HBsAg seropositivity was the only factor correlated to the delta PLT count change
      per year (beta: -10.193; CI: -16.752-3.635; P = 0.003) among patients with F3-4.
      CONCLUSIONS: Platelet counts recovered after hepatitis C virus eradication. HBV
      dual infection disrupted PLT count recovery, especially in CHC patients with
      advanced liver disease.

PMID- 29023928
TI  - Evaluation of medical and dental visits in New York City: Opportunities to
      identify persons with and at risk for diabetes mellitus in dental settings.
AB  - OBJECTIVE: The identification of persons with or at risk for chronic diseases is
      a new practice paradigm for oral healthcare. Diabetes mellitus (DM) is a chronic
      disease of particular importance to oral health providers. This study sought to
      understand healthcare utilization patterns that would support the introduction of
      this new practice paradigm. METHODS: The primary and oral healthcare utilization
      patterns of New York City (NYC) adults were assessed using data collected from
      the 2013 NYC Community Health Survey. We stratified healthcare utilization
      patterns by type of provider, insurance, DM diagnosis and DM modifiable risk
      factors. RESULTS: Of 6.4 million NYC adults, an estimated 676 000 (10.5%)
      reported a previous diagnosis of DM, and 3.9 million (69.5%) were identified with
      one or more modifiable risk factor for DM. Of these at risk individuals, 2.2
      million (58.9%) received dental services in the past 12 months, and 545 000
      (14.3%) did not see a primary care provider during the same period. Of the
      approximately 1.16 million adults without health insurance, an estimated 338 000
      (26.2%) had a dental visit only. CONCLUSION: Healthcare utilization patterns in
      this urban setting suggest that oral healthcare providers can support the
      identification of patients with and at risk for DM who may otherwise not have the
      opportunity for screening.

PMID- 29023930
TI  - Evaluation and Treatment of Acute and Subacute Hearing Loss: A Review of
      Pharmacotherapy.
AB  - Among various forms of hearing loss, there are acute (within 72 hrs) or subacute
      (weeks to months) presentations that may be reversible with early pharmacological
      intervention. The workup of a patient presenting with hypoacusia includes the
      usual history and physical examination in conjunction with an audiometric
      assessment in order to categorize the hearing loss as conductive, sensorineural,
      or mixed. Sudden sensorineural hearing loss and autoimmune inner ear disease are
      acute and subacute forms of sensorineural hypoacusia most likely to be reversed
      with prompt pharmacological intervention. Systemic or local corticosteroid
      therapy has the most evidence of benefit in patients with sudden sensorineural
      hypoacusia and is the best available first line therapy noted in clinical
      practice guidelines. Alternative immunosuppressant therapies have not been well
      studied, and many have serious toxicities that further complicate the benefit
      risk assessment. There are no randomized comparisons of corticosteroid dosing
      regimens that evaluated clinically important outcomes, so expert opinion must
      serve as the basis for dosing recommendations. Clinicians need to involve
      patients with hypoacusia in the shared decision-making process, since partial or
      complete reversal of hearing loss can have substantial quality-of-life
      implications for affected patients.

PMID- 29023929
TI  - Friendship in War: Camaraderie and Prevention of Posttraumatic Stress Disorder
      Prevention.
AB  - Aspects of social support during combat deployment, such as unit cohesion, have
      been shown to affect later posttraumatic stress disorder (PTSD) development among
      veterans. We utilized a longitudinal database to assess how relationship quality
      with fellow soldiers in World War II (WWII) might be linked with postwar PTSD
      symptoms. Data were available on 101 men who experienced combat exposure in WWII,
      documented through postwar assessment. Upon study entry (1939 to 1942), data were
      collected on the quality of participants' early childhood relationships and their
      emotional adjustment during college. Data on WWII experiences were collected in
      1946. Relationship quality with fellow soldiers in WWII was examined as a
      moderator of the link between combat exposure and postwar PTSD symptoms. Prewar
      emotional adjustment was examined as a mediator between quality of childhood
      relationships and subsequent quality of relationships quality with fellow
      soldiers during war. Better quality relationships with fellow soldiers attenuated
      (i.e., moderated) the link between combat exposure severity and PTSD symptom
      count, explaining a significant percent of the variance, R2 = .19, p < .001.
      There was also a significant indirect mediation effect of childhood relationship
      quality on relationships with soldiers through prewar emotional adjustment, ab =
      0.02, 95% BCa CI [0.01, 0.05]. Results suggest that better peer relationship
      quality during deployment may reduce the likelihood of subsequent PTSD symptom
      development, and that the quality of early relationships may set the stage for
      better relationships during stressful contexts such as war. These findings have
      implications for PTSD risk factor screening prior to deployment, and underscore
      the importance of interpersonal support among soldiers during deployment.

PMID- 29023931
TI  - Evaluation of the right and left ventricles: An integrated approach measuring the
      area, length, and width of the chambers in normal fetuses.
AB  - INTRODUCTION: The purpose of this study was to simultaneously measure with
      speckle tracking software the end-diastolic ventricular area (A), basal
      transverse width (BW), mid-chamber transverse width (MW), and basal-apical length
      (BAL) in normal fetuses and those with pathology. METHODS: The 4-chamber view of
      the fetal heart was obtained in 200 control fetuses between 20 and 40 weeks of
      gestation and in 9 third-trimester fetuses with heart malformations. The mean and
      standard deviation for the A, BW, MW, and BAL were computed from the control
      fetuses and Z scores computed from the 9 fetuses with cardiac malformations.
      RESULTS: The A, BAL, BW, and MW were correlated with 7 somatic and age
      independent variables (R2  = .63-.85). The highest R2 values occurred for the
      head circumference, estimated fetal weight, and ultrasound mean gestational age
      (.82-.85). Z-score values and centiles from the 9 fetuses with cardiac
      malformations suggested that the A, BW, MW, and BAL were below or above the 5th
      and 95th centiles as expected for the corresponding ventricular pathology.
      CONCLUSIONS: This study reports an integrated approach to evaluate the end
      diastolic size of the right and left ventricular chambers and demonstrated
      clinical utility in fetuses with cardiac malformations.

PMID- 29023932
TI  - Xanthogranulomatous cholecystitis shows overlapping histological features with
      IgG4-related cholecystitis.
AB  - AIMS: Xanthogranulomatous cholecystitis (XGC), an unusual histological variant of
      chronic cholecystitis, is characterised by mixed foamy histiocytic and
      lymphoplasmocytic infiltration and fibrosis. Radiologically, the poorly defined
      nodular growth pattern often leads to the misinterpretation of XGC as gallbladder
      cancer. In this study, we aimed to identify the relationship of XGC with IgG4
      related cholecystitis. METHODS AND RESULTS: We re-evaluated 57 surgically
      resected XGCs and 104 conventional chronic cholecystitis cases, according to the
      histological features observed in IgG4-related disease, including
      lymphoplasmocytic infiltration, storiform fibrosis, obliterative phlebitis, and
      IgG4-positive plasma cells. XGCs contained a significantly increased mean number
      of IgG4-positive plasma cells [34.8/high-power field (HPF)] as compared with
      conventional chronic cholecystitis (4.8/HPF; P < 0.001), and 16 XGCs (28%)
      harboured >50 IgG4-positive cells per HPF. Nine XGCs (16%), including one case
      with IgG4-related autoimmune pancreatitis, showed 'the histological features
      suggestive of IgG4-related disease', as described in the consensus statement
      regarding this condition. Extracholecystic inflammatory extension (seven cases, P
      = 0.009) and mass-forming lesions (eight cases, P < 0.001) were more frequently
      seen in XGC cases with histological features suggestive of IgG4-related disease
      than in cases without those microscopic changes. CONCLUSIONS: XGCs with IgG4
      positive cell infiltration are considered to be mimickers, as xanthogranulomatous
      inflammation generally contradicts a diagnosis of IgG4-related disease and is
      weakly associated with other typical organ manifestations of IgG4-related
      disease. However, XGC may be a concurrent condition, particularly in patients
      with IgG4-related disease in other organs.

PMID- 29023933
TI  - MicroRNA 15a/16-1 suppresses aryl hydrocarbon receptor-dependent interleukin-22
      secretion in CD4+ T cells and contributes to immune-mediated organ injury.
AB  - : Interleukin-22 (IL-22), as a link between leukocytic and nonleukocytic cells,
      has gained increasing attention for its pronounced tissue-protective properties.
      MicroRNAs, emerging as crucial immune modulators, have been reported to be
      involved in the production and action of various cytokines. However, the precise
      control of IL-22 by microRNAs and its subsequent actions remained to be
      elucidated. In this study, we found a negative correlation between the expression
      of microRNA 15a/16-1 (miR-15a/16-1) and IL-22 in the model of concanavalin A
      induced, immune-mediated liver injury. Knockout of miR-15a/16-1 ameliorated liver
      injury in an IL-22-dependent manner. Further results revealed that cluster of
      differentiation 4-positive (CD4+ ) T cells were the major source of IL-22 during
      liver injury and that the aryl hydrocarbon receptor was the direct target of miR
      15a/16-1 in CD4+ T cells. In vivo and in vitro data showed that miR-15a/16-1
      knockout CD4+ T cells produced more IL-22, while overexpression of miR-15a/16-1
      down-regulated the IL-22 production by inhibiting the aryl hydrocarbon receptor.
      Moreover, transfer of miR-15a/16-1 knockout CD4+ T cells promoted tissue repair
      compared to wild-type CD4+ T cells by up-regulating IL-22. In addition, as a
      synergistic effect, IL-22 could down-regulate miR-15a/16-1 expression by
      activating phosphorylated signal transducer and activator of transcription 3-c
      myc signaling, and the decrease of miR-15a/16-1 in damaged hepatocytes
      contributed to IL-22-mediated tissue repair by reducing cell apoptosis and
      promoting cell proliferation. As further proof, we demonstrated the role of miR
      15a/16-1 in controlling IL-22 production and IL-22-mediated reconstruction of the
      intestinal epithelial barrier in a dextran sodium sulfate-induced colitis model.
      CONCLUSION: Our results suggest that miR-15a/16-1 acts as a essential regulator
      of IL-22 and that the miR-15a/16-1-aryl hydrocarbon receptor-IL-22 regulatory
      axis plays a central role in tissue repair; modulation of miR-15a/16-1 might hold
      promise in developing new strategies to enhance IL-22-mediated tissue repair.
      (Hepatology 2018;67:1027-1040).

PMID- 29023934
TI  - Spontaneous Emergence of Legibility in Writing Systems: The Case of Orientation
      Anisotropy.
AB  - Cultural forms are constrained by cognitive biases, and writing is thought to
      have evolved to fit basic visual preferences, but little is known about the
      history and mechanisms of that evolution. Cognitive constraints have been
      documented for the topology of script features, but not for their orientation.
      Orientation anisotropy in human vision, as revealed by the oblique effect,
      suggests that cardinal (vertical and horizontal) orientations, being easier to
      process, should be overrepresented in letters. As this study of 116 scripts
      shows, the orientation of strokes inside written characters massively favors
      cardinal directions, and it is organized in such a way as to make letter
      recognition easier: Cardinal and oblique strokes tend not to mix, and mirror
      symmetry is anisotropic, favoring vertical over horizontal symmetry. Phylogenetic
      analyses and recently invented scripts show that cultural evolution over the last
      three millennia cannot be the sole cause of these effects.

PMID- 29023936
TI  - Understanding patterns of invasion: a novel approach to assessment of podoplanin
      expression in the prediction of lymph node metastasis in oral squamous cell
      carcinoma.
AB  - AIMS: Cellular motility is considered to be central to the process of metastasis,
      and podoplanin expression can be explored as a prospective link, owing to its
      ability to modulate the actin cytoskeleton. We aimed to evaluate the tumoral
      expression of D2-40 (monoclonal antibody against podoplanin) in pathologically
      neck-node-negative/positive cases (pN0/N+) to characterise the pattern of
      invasion, potentially explaining the role of various patterns of invasion in
      causing tumour metastasis. METHODS AND RESULTS: Paraffin-embedded tissue blocks
      of 60 oral squamous cell carcinoma cases of known nodal status were selected for
      immunohistochemical staining of tumour (invasive front) by D2-40 along with
      routine staining by haematoxylin and eosin. Various staining patterns were
      assessed and evaluated for D2-40 expression, and correlated with nodal status.
      Tumoral D2-40 expression correspondingly increased with nodal metastasis (P =
      0.261). Furthermore, D2-40 staining was more efficient in detecting individual
      tumour cells, and also characterised the motility factor irrespective of the
      pattern of invasion (P = 0.001). The pattern of D2-40 staining did not show a
      significant association with tumour grade, indicating that motility is an
      overlooked, albeit important, component of the pattern of invasion in routine
      histological grading. CONCLUSIONS: D2-40 expression successfully identifies the
      motility profile of tumour, irrespective of the pattern of invasion. The presence
      of larger motile islands in the tumour cohort supports the concept of 'collective
      cell migration'. Podoplanin also aids evasion of immune responses by inducing
      platelet aggregation over tumour cells, thereby favouring distant metastasis. A
      multivariate model using immunohistochemical staining with D2-40 provides greater
      sensitivity for the prediction of lymph node metastasis.

PMID- 29023937
TI  - Can botulinum toxin cause chronic muscle weakness?

PMID- 29023938
TI  - A Pharmacist-Led Program to Evaluate and Reduce Polypharmacy and Potentially
      Inappropriate Prescribing in Older HIV-Positive Patients.
AB  - OBJECTIVE: The goal of this pharmacist-led study was to utilize two validated
      instruments, Beers Criteria and Screening Tool of Older Persons' Potentially
      Inappropriate Prescriptions (STOPP), to assess potentially inappropriate
      prescribing (PIP) in older patients infected with the human immunodeficiency
      virus (HIV) and evaluate pharmacist interventions. DESIGN: Prospective randomized
      interventional trial. SETTING: Large urban clinic providing interdisciplinary
      primary and HIV care for ~2700 HIV-positive publicly insured patients. DATA
      SOURCE: A computerized electronic record search was conducted for all patients
      who met the two search criteria: 50 years and older, and a primary care
      appointment within the last 12 months. PATIENTS: After identification of 857
      patients meeting the search criteria, 324 patients were randomly selected and
      contacted, resulting in 248 patients assessed. MEASUREMENTS AND MAIN RESULTS:
      Patients had a mean age of 58 years, 71% male, 44% white, and a mean CD4 count of
      536 cells/mm3 . Common comorbidities included hypertension (56%), depression
      (52%), asthma/chronic obstructive pulmonary disease (48%), dyslipidemia (39%),
      coronary artery disease (27%), and diabetes (22%). Patients sampled were
      prescribed a mean of 11.6 +/- 5.7 concomitant medications (excluding
      antiretrovirals) with 35% receiving at least 16 medications. PIP was identified
      in 54% and 63% of patients using the STOPP and Beers Criteria, respectively.
      Twenty-five contraindicated drug interactions were identified in 20 patients.
      After the pharmacist visit, at least 69% of patients had at least one medication
      discontinued with almost 10% having six or more medications discontinued. More
      than 40% of patients had at least one Beers or STOPP criteria that required
      immediate correction by the pharmacist. CONCLUSIONS: Results suggest that
      targeting individuals with 11 or more chronic medications would have the highest
      yield and greatest impact. Pharmacist-led review of medication prescribing using
      Beers and STOPP criteria revealed a large number of PIP, many amenable to
      immediate clinical pharmacist intervention.

PMID- 29023935
TI  - Exosome miR-335 as a novel therapeutic strategy in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a common and deadly cancer. Most cases of HCC
      arise in a cirrhotic/fibrotic liver, indicating that environment may play a
      paramount role in cancer genesis. Previous studies from our group and others have
      shown that, in desmoplastic cancers, there is a rich intercellular communication
      between activated, cancer-associated fibroblasts and cancer cells. Moreover,
      extracellular vesicles (EVs), or exosomes, have been identified as an important
      arm of this intercellular communication platform. Finally, these studies have
      shown that EVs can carry microRNA (miR) species in vivo and deliver them to
      desmoplastic cancers. The precise role played by activated liver
      fibroblasts/stellate cells in HCC development is insufficiently known. Based on
      previous studies, it appears plausible that activated fibroblasts produce signals
      carried by EVs that promote HCC genesis. In the current study, we first
      hypothesized and then demonstrated that stellate cell-derived EVs 1) can be
      loaded with an miR species of choice (miR-335-5p); 2) are taken up by HCC cells
      in vitro and more importantly in vivo; 3) can supply the miR-335-5p cargo to
      recipient HCC cells in vitro as well as in vivo; and 4) inhibit HCC cell
      proliferation and invasion in vitro as well as induce HCC tumor shrinkage in
      vivo. Finally, we identified messenger RNA targets for miR-335 that are down
      regulated after treatment with EV-miR-335-5p. This study informs potential
      therapeutic strategies in HCC, whereby stellate cell-derived EVs are loaded with
      therapeutic nucleic acids and delivered in vivo. (Hepatology 2018;67:940-954).

PMID- 29023939
TI  - Comparing a novel hand held device (Peritron+) to standard urodynamics in
      measuring intravesical pressure.
AB  - AIMS: Peritron+ is a new handheld device, which can be attached to a urethral
      catheter to measure intravesical pressures (Pves). The goal of this study was to
      assess if Pves recorded by standard urodynamics (UDs) are comparable to those
      recorded by the Peritron+. METHODS: Patients with voiding dysfunction and an
      indication for UD underwent measurement of Pves with nonvideo UD and Peritron+.
      Pves were recorded at volumes of 50, 100, and 200 mL for the supine and sitting
      positions. A failure of the Peritron+ was considered to be a discrepancy of Pves
      values >3 cmH2 O between Peritron+ and UD recordings. Two-way ANOVA was used to
      assess for statistical significance. P-values < 0.05 were considered significant.
      RESULTS: Ten female patients, mean age 51 years old, were enrolled in the study.
      The difference in Pves measurements between Peritron+ and UD were <=3 cmH2 O at
      all bladder volumes measured in a supine and sitting positions. There were no
      adverse events and there were no malfunctions of the Peritron+ device during the
      study. CONCLUSIONS: Peritron+ handheld device accurately assessed Pves at
      different intravesical volumes when compared to UD measurements. The Peritron+ is
      a simple and safe device, which can be used in the office by a clinician and at
      home by a patient to monitor Pves and help to select patients who may require
      standard UD re-evaluation. This will be a valuable tool in managing patients with
      neurogenic and nonneurogenic bladders who are at a risk of upper urinary tract
      deterioration.

PMID- 29023940
TI  - Milia: a useful clinical marker of CYLD mutation carrier status.

PMID- 29023941
TI  - Mechanical Ventilation for Duchenne Muscular Dystrophy: Sinner or Saint?

PMID- 29023942
TI  - A review of tensor-based methods and their application to hospital care data.
AB  - In many situations, a researcher is interested in the analysis of the scores of a
      set of observation units on a set of variables. However, in medicine, it is very
      frequent that the information is replicated at different occasions. The occasions
      can be time-varying or refer to different conditions. In such cases, the data can
      be stored in a 3-way array or tensor. The Candecomp/Parafac and Tucker3 methods
      represent the most common methods for analyzing 3-way tensors. In this work, a
      review of these methods is provided, and then this class of methods is applied to
      a 3-way data set concerning hospital care data for a hospital in Rome (Italy)
      during 15 years distinguished in 3 groups of consecutive years (1892-1896, 1940
      1944, 1968-1972). The analysis reveals some peculiar aspects about the use of
      health services and its evolution along the time.

PMID- 29023943
TI  - Experimental Evidence From Newborn Chicks Enriches Our Knowledge on Human Spatial
      Numerical Associations.
AB  - Nunez and Fias raised concerns on whether our results demonstrate a linear number
      space mapping. Patro and Nuerk urge caution on the use of animal models to
      understand the origin (cultural vs. biological) of the orientation of spatial
      numerical association. Here, we discuss why both objections are unfounded.

PMID- 29023944
TI  - Reconsidering the H&E stain as the gold standard in assessing the depth of burn
      wounds.
AB  - While histological examination is considered by most as the gold standard for
      burn depth assessment, it has no practical use in the clinical setting. It has,
      however, been used in the research setting, as a mean for evaluating emerging
      techniques of depth measurement. Due to the limitations of the H&E stain, other
      stains have also been explored, such as lactate dehydrogenase (LDH), as presented
      in this issue, in "Improving the Histologic Characterization of Burn Depth." As
      the determination of burn depth is not a typical subject in dermatopathology, a
      summary of selected techniques and the possible role for the LDH stain in future
      research, is described herein.

PMID- 29023945
TI  - MicroRNA-29a inhibits proliferation and motility of schwannoma cells by targeting
      CDK6.
AB  - MicroRNA-29 (miR-29) family is involved in various types of cancer regulation.
      Although miR-29 family was shown to play an inhibitory role in tumorigenesis, the
      effect of miR-29a expression on schwannoma cells still remains unclear. In this
      study, we aimed to explore the role of miR-29 family in schwannoma. The
      expressions of miR-29a, miR-29b, and miR-29c were detected in the Schwann tissues
      and cell lines using qRT-PCR. The effect of miR-29a, miR-29b, and miR-29c on cell
      viability, migration, invasion, and apoptosis was tested. Then, the regulatory
      relationship between miR-29a and CKD6 was detected using qRT-PCR, Western blot,
      and luciferase assay. Finally, the phosphorylation levels of mainly factors in
      JNK and p38MAPK/ERK pathways were analyzed by Western blot. The expression of miR
      29a, miR-29b, and miR-29c was downregulated in Schwann tissues and cell lines.
      Cell viability, migration, invasion were decreased, while apoptosis was increased
      when miR-29a, miR-29b, and miR-29c overexpression. We further found that miR-29a
      negatively regulated expression of CDK6. Then, knockdown of miR-29a promoted cell
      viability, migration, invasion, and inhibited apoptosis in schwannoma cells by
      upregulating CDK6 expression. In addition, the overexpression of miR-29a
      downregulated CDK6 expression by deactivation of JNK and p38MAPK/ERK pathways.
      Our data suggested that miR-29a could play an important role in inhibiting
      proliferation and motility of cancerous Schwann cells, and may suppress tumor
      growth through upregulation of CDK6.

PMID- 29023946
TI  - A novel recombinant anti-epidermal growth factor receptor peptide vaccine capable
      of active immunization and reduction of tumor volume in a mouse model.
AB  - Over-expression of epidermal growth factor receptor (EGFR) has been reported in a
      number of human malignancies. Strong expression of this receptor has been
      associated with poor survival in many such patients. Active immunizations that
      elicit antibodies of the desired type could be an appealing alternative to
      conventional passive immunization. In this regard, a novel recombinant peptide
      vaccine capable of prophylactic and therapeutic effects was constructed. A novel
      fusion recombinant peptide base vaccine consisting of L2 domain of murine extra
      cellular domain-EGFR and EGFR mimotope (EM-L2) was constructed and its
      prophylactic and therapeutic effects in a Lewis lung carcinoma mouse (C57/BL6)
      model evaluated. Constructed recombinant peptide vaccine is capable of reacting
      with anti-EGFR antibodies. Immunization of mice with EM-L2 peptide resulted in
      antibody production against EM-L2. The constructed recombinant peptide vaccine
      reduced tumor growth and increased the survival rate. Designing effective peptide
      vaccines could be an encouraging strategy in contemporary cancer immunotherapy.
      Investigating the efficacy of such cancer immunotherapy approaches may open
      exciting possibilities concerning hyperimmunization, leading to more promising
      effects on tumor regression and proliferation.

PMID- 29023947
TI  - Genetic characterization of an avian H4N6 influenza virus isolated from the Izumi
      plain, Japan.
AB  - An influenza A virus of H4N6 subtype was isolated from the Izumi plain, Japan, in
      2013. Genetic analyses revealed that two viral genes (M and NS gene segments) of
      this isolate were genetically distinct from those of the H4N6 virus isolated from
      the same place in 2012. Furthermore, three viral genes (PB2, PB1 and M gene
      segments) of this isolate share high similarity with those of the North American
      isolates of 2014. These results suggest a high frequency of genetic reassortment
      of avian influenza viruses in Asian waterfowl and intercontinental movements of
      avian influenza viruses via migratory waterfowl.

PMID- 29023949
TI  - More about molluscum pendulum/acrochordons in tuberous sclerosis complex.

PMID- 29023948
TI  - Linear IgA bullous dermatosis associated with amyotrophic lateral sclerosis.

PMID- 29023950
TI  - Synthesis and evaluation of Tc-99m and fluorescence-labeled elastin-derived
      peptide, VAPG for multimodal tumor imaging in murine tumor model.
AB  - We developed a Tc-99m and fluorescence-labeled peptide, Tc-99m TAMRA-GHEG-ECG
      VAPG to target tumor cells and evaluated the diagnostic performance as a dual
      modality imaging agent for tumor in a murine model. TAMRA-GHEG-ECG-VAPG was
      synthesized by using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA
      GHEG-ECG-VAPG with Tc-99m was done by using ligand exchange via tartrate. Binding
      affinity and in vitro cellular uptake studies were performed. Gamma camera
      imaging, biodistribution, and ex vivo imaging studies were performed in murine
      models with SW620 tumors. Tumor tissue slides were prepared and analyzed with
      immunohistochemistry by using confocal microscopy. After radiolabeling procedures
      with Tc-99m, Tc-99m TAMRA-GHEG-ECG-VAPG complexes were prepared in high yield
      (>96%). The Kd of Tc-99m TAMRA-GHEG-ECG-VAPG determined by saturation binding was
      16.8 +/- 3.6 nM. Confocal microscopy images of SW620 cells incubated with TAMRA
      GHEG-ECG-VAPG showed strong fluorescence in the cytoplasm. Gamma camera imaging
      revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-VAPG in tumors. Tumor uptake
      was effectively blocked by the coinjection of an excess concentration of VAPG.
      Specific uptake of Tc-99m TAMRA-GHEG-ECG-VAPG was confirmed by biodistribution,
      ex vivo imaging, and immunohistochemistry stain studies. In vivo and in vitro
      studies revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-VAPG in tumor cells.
      Tc-99m TAMRA-GHEG-ECG-VAPG has potential as a dual-modality tumor imaging agent.

PMID- 29023951
TI  - Synthesis, 99m Tc-labeling, and preliminary biological evaluation of DTPA
      melphalan conjugates.
AB  - Melphalan (MFL) is a typical nitrogen mustard for the treatment of many types of
      cancer. For the purpose to develop novel 99m Tc-labeled tumor imaging agents with
      SPECT, MFL was directly labeled by 99m Tc using diethylene triamine pentacetate
      acid (DTPA) as bifunctional chelating agent. The novel ligands were successfully
      synthesized by conjugation of DTPA to MFL to get monosubstituted DTPA-MFL and bis
      substituted DTPA-2MFL. Radiolabeling was performed in high yield to get 99m Tc
      DTPA-MFL and 99m Tc-DTPA-2MFL, respectively, which were hydrophilic and stable at
      room temperature. The high initial tumor uptake with retention, good tumor/muscle
      ratios, and satisfactory scintigraphic images suggested the potential of 99m Tc
      DTPA-MFL and 99m Tc-DTPA-2MFL for tumor imaging. However, the slow normal tissue
      clearance would be a great obstacle. Further modification on the linker and/or
      99m Tc-chelate to improve the tumor targeting efficacy and in vivo kinetic
      profiles is currently in progress.

PMID- 29023953
TI  - Comment On: Family Involvement in Managing Violence of Mental Health Patients.

PMID- 29023952
TI  - Pharmacokinetics and electrophysiological effects of sotalol hydrochloride in
      horses.
AB  - BACKGROUND: Arrhythmias in horses may require long-term anti-arrhythmic therapy.
      Unfortunately, oral anti-arrhythmic drugs for use in horses are currently scarce.
      In human patients and small animals, sotalol, a beta-blocker with class III anti
      arrhythmic properties, is often used for long-term treatment. OBJECTIVES: To
      determine the pharmacokinetics of sotalol at multiple oral dosages in unfasted
      horses, as well as the effects on electro- and echocardiographic measurements,
      right atrial and ventricular monophasic action potential (MAP) and effective
      refractory period (ERP). STUDY DESIGN: Placebo controlled, double-blinded
      experiment. MATERIALS AND METHODS: Six healthy, unfasted Warmblood horses were
      given either 0, 2, 3 or 4 mg/kg bodyweight (bwt) sotalol orally (PO) twice daily
      (bid) for 9 days in a randomised cross-over design. Echocardiography and surface
      electrocardiography were performed and plasma concentrations of sotalol and right
      atrial and right ventricular MAPs and ERPs were determined at steady-state
      conditions. Statistical analysis was performed using a repeated measures
      univariate analysis with post hoc Bonferroni corrections. RESULTS: Calculated
      mean steady-state plasma concentrations determined by nonlinear mixed-effect
      modelling were 287 (range 234-339), 409 (359-458) and 543 (439-646) ng/mL for 2,
      3 and 4 mg/kg bwt sotalol PO bid respectively. Sotalol significantly increased
      the QT interval and ERPs, but, despite increasing plasma concentrations, higher
      dosages did not result in a progressive increase in QT interval or ERPs.
      Echocardiographic and other electrocardiographic measurements did not change
      significantly. MAP durations at 90% repolarisation were not significantly
      different during sotalol treatment. Besides transient local sweating, no side
      effects were noted. MAIN LIMITATIONS: Study size and ad libitum feeding of hay.
      CONCLUSIONS: Sotalol at a dose of 2, 3 and 4 mg/kg bwt PO bid increases the QT
      interval and ERP and might be a useful drug for long-term anti-arrhythmic therapy
      in horses.

PMID- 29023954
TI  - History of champions for changes in mental health and substance use parity.

PMID- 29023955
TI  - Are Insurance Companies Overstepping Boundaries and Ethics?

PMID- 29023956
TI  - Reply.

PMID- 29023957
TI  - The ethics of public policy RCTs: The principle of policy equipoise.
AB  - In this article, I ask whether a principle analogous to the principle of clinical
      equipoise should govern the design and conduct of RCTs evaluating the
      effectiveness of policy interventions. I answer this question affirmatively, and
      introduce and defend the principle of policy equipoise. According to this
      principle, all arms of a policy RCT must be, at minimum, in a state of equipoise
      with the best proven policy that is also morally and practically attainable and
      sustainable. For all arms of a policy RCT, policy experts must either (1)
      reasonably disagree about whether the trial arms are more effective than this
      policy, or (2) know that they are.

PMID- 29023959
TI  - Pembrolizumab for metastatic hepatocellular carcinoma following live donor liver
      transplantation: The silver bullet?

PMID- 29023960
TI  - "Meal realities" - An ethnographic exploration of hospital mealtime environment
      and practice.
AB  - AIM: To explore and understand patterns of mealtime culture, environment and
      social practice from the perspective of staff, volunteers and visitors on the
      hospital ward. BACKGROUND: Inadequate food intake is a common and complex problem
      in hospital and can lead to malnutrition. Mealtime interventions have been
      implemented to address this problem with limited success. A better understanding
      of mealtime environment and practice is needed to ascertain which interventions
      are more likely to be effective in addressing inadequate food intake in hospital.
      DESIGN: A qualitative, ethnographic approach was used to promote a comprehensive
      understanding of mealtime environment and practice. METHODS: Sixty-seven hours of
      fieldwork was conducted August-October 2015. More than 150 participants were
      observed and 61 unique participants were interviewed in 75 interviews. Data
      analysis followed an inductive, thematic approach, informed by systems and
      complexity theory. FINDINGS: Themes of "patient centredness" and "system" and
      their disharmonious interrelationship emerged. Staff, volunteers and visitors
      strive for patient centredness at mealtimes. The routine and structured nature of
      the meal and care systems was constantly in tension with providing patients the
      care they needed. CONCLUSION: The findings of this study expose the challenges
      associated with maintaining patient centredness at mealtimes in complex
      healthcare and foodservice systems. This facilitates a better understanding of
      why inadequate food intake is difficult to address in the hospital setting and
      highlights the need to support strategies that approach foodservice processes and
      nutritional care as complex and non-linear.

PMID- 29023958
TI  - Stroke-induced chronic systolic dysfunction driven by sympathetic overactivity.
AB  - OBJECTIVE: Cardiac diseases are established risk factors for ischemic stroke
      incidence and severity. Conversely, there is increasing evidence that brain
      ischemia can cause cardiac dysfunction. The mechanisms underlying this neurogenic
      heart disease are incompletely understood. Although it is established that
      ischemic stroke is associated with cardiac arrhythmias, myocardial damage,
      elevated cardiac enzymes, and plasma catecholamines in the acute phase, nothing
      is known about the delayed consequences of ischemic stroke on cardiovascular
      function. METHODS: To determine the long-term cardiac consequences of a focal
      cerebral ischemia, we subjected young and aged mice to a 30-minute transient
      middle cerebral artery occlusion and analyzed cardiac function by serial
      transthoracic echocardiography and hemodynamic measurements up to week 8 after
      surgery. Finally, animals were treated with metoprolol to evaluate a
      pharmacologic treatment option to prevent the development of heart failure.
      RESULTS: Focal cerebral ischemia induced a long-term cardiac dysfunction with a
      reduction in left ventricular ejection fraction and an increase in left
      ventricular volumes; this development was associated with higher peripheral
      sympathetic activity. Metoprolol treatment prevented the development of chronic
      cardiac dysfunction by decelerating extracellular cardiac remodeling and
      inhibiting sympathetic signaling relevant to chronic autonomic dysfunction.
      INTERPRETATION: Focal cerebral ischemia in mice leads to the development of
      chronic systolic dysfunction driven by increased sympathetic activity. If these
      results can be confirmed in a clinical setting, treating physicians should be
      attentive to clinical signs of heart failure in every patient after ischemic
      stroke. Therapeutically, the successful beta-blockade with metoprolol in mice
      could also have future clinical implications. Ann Neurol 2017;82:729-743.

PMID- 29023962
TI  - Microphthalmia with linear skin defects (MLS) syndrome: familial presentation.

PMID- 29023961
TI  - Clinical significance of small-bowel villous edema in patients with liver
      cirrhosis: A capsule endoscopy study.
AB  - BACKGROUND AND AIM: The relationship between the presence of villous edema (VE)
      in portal hypertensive enteropathy and clinical factors remains unclear. The aim
      of this study was to reveal the clinical factors related to VE in patients with
      liver cirrhosis (LC), and investigate the clinical significance of VE. METHODS:
      Between February 2009 and September 2016, 363 consecutive patients with LC
      underwent capsule endoscopy for diagnosing portal hypertensive enteropathy at
      Hiroshima University Hospital. We evaluated the relationship between the presence
      of VE and patients' clinical characteristics, findings of
      esophagogastroduodenoscopy and computed tomography, and survival time. RESULTS:
      Villous edema was observed in 131 patients (36%), and severe lesions were found
      in 71 (20%). The presence of VE was significantly greater in patients with Child
      Pugh classification B or C, esophageal varices, portal hypertensive gastropathy
      (PHG), ascites, portal vein thrombosis (PVT), and splenomegaly. In multivariate
      analysis, Child-Pugh class B or C, esophageal varices, PVT, and splenomegaly were
      significant predictive factors for the presence of VE. Severe VE was
      significantly greater in patients with Child-Pugh class B or C, serum albumin
      level <= 3.2 mg/dL, PHG, and PVT. In multivariate analysis, PHG, Child-Pugh class
      B or C, PVT, were significant predictive factors for severe VE. CONCLUSIONS:
      Clinical factors related to portal hypertension were significantly correlated
      with VE. In particular PVT was correlated with the appearance and exacerbation of
      VE. Periodic capsule endoscopy in LC patients may lead to early detection of
      portal hypertension and PVT.

PMID- 29023964
TI  - Linguistic and Perceptual Mapping in Spatial Representations: An Attentional
      Account.
AB  - Building on evidence for embodied representations, we investigated whether
      Spanish spatial terms map onto the NEAR/FAR perceptual division of space. Using a
      long horizontal display, we measured congruency effects during the processing of
      spatial terms presented in NEAR or FAR space. Across three experiments, we
      manipulated the task demands in order to investigate the role of endogenous
      attention in linguistic and perceptual space mapping. We predicted congruency
      effects only when spatial properties were relevant for the task (reaching
      estimation task, Experiment 1) but not when attention was allocated to other
      features (lexical decision, Experiment 2; and color, Experiment 3). Results
      showed faster responses for words presented in Near-space in all experiments.
      Consistent with our hypothesis, congruency effects were observed only when a
      reaching estimate was requested. Our results add important evidence for the role
      of top-down processing in congruency effects from embodied representations of
      spatial terms.

PMID- 29023965
TI  - A Framework for Understanding Uncertainty in Seismic Risk Assessment.
AB  - A better understanding of the uncertainty that exists in models used for seismic
      risk assessment is critical to improving risk-based decisions pertaining to
      earthquake safety. Current models estimating the probability of collapse of a
      building do not consider comprehensively the nature and impact of uncertainty.
      This article presents a model framework to enhance seismic risk assessment and
      thus gives decisionmakers a fuller understanding of the nature and limitations of
      the estimates. This can help ensure that risks are not over- or underestimated
      and the value of acquiring accurate data is appreciated fully. The methodology
      presented provides a novel treatment of uncertainties in input variables, their
      propagation through the model, and their effect on the results. The study
      presents ranges of possible annual collapse probabilities for different case
      studies on buildings in different parts of the world, exposed to different levels
      of seismicity, and with different vulnerabilities. A global sensitivity analysis
      was conducted to determine the significance of uncertain variables. Two key
      outcomes are (1) that the uncertainty in ground-motion conversion equations has
      the largest effect on the uncertainty in the calculation of annual collapse
      probability; and (2) the vulnerability of a building appears to have an effect on
      the range of annual collapse probabilities produced, i.e., the level of
      uncertainty in the estimate of annual collapse probability, with less vulnerable
      buildings having a smaller uncertainty.

PMID- 29023963
TI  - Prediction of phenotypic severity in mucopolysaccharidosis type IIIA.
AB  - OBJECTIVE: Mucopolysaccharidosis IIIA or Sanfilippo disease type A is a
      progressive neurodegenerative disorder presenting in early childhood, caused by
      an inherited deficiency of the lysosomal hydrolase sulfamidase. New missense
      mutations, for which genotype-phenotype correlations are currently unknown, are
      frequently reported, hampering early prediction of phenotypic severity and
      efficacy assessment of new disease-modifying treatments. We aimed to design a
      method to determine phenotypic severity early in the disease course. METHODS:
      Fifty-three patients were included for whom skin fibroblasts and data on disease
      course and mutation analysis were available. Patients were phenotypically
      characterized on clinical data as rapidly progressing or slowly progressing.
      Sulfamidase activity was measured in fibroblasts cultured at 37  degrees C and at
      30  degrees C. RESULTS: Sulfamidase activity in fibroblasts from patients
      homozygous or compound heterozygous for a combination of known severe mutations
      remained below the limit of quantification under both culture conditions. In
      contrast, sulfamidase activity in fibroblasts from patients homozygous or
      compound heterozygous for a known mild mutation increased above the limit of
      quantification when cultured at 30  degrees C. With division on the basis of the
      patients' phenotype, fibroblasts from slowly progressing patients could be
      separated from rapidly progressing patients by increase in sulfamidase activity
      when cultured at 30  degrees C (p < 0.001, sensitivity = 96%, specificity = 93%).
      INTERPRETATION: Phenotypic severity strongly correlates with the potential to
      increase sulfamidase activity in fibroblasts cultured at 30  degrees C, allowing
      reliable distinction between patients with rapidly progressing or slowly
      progressing phenotypes. This method may provide an essential tool for assessment
      of treatment effects and for health care and life planning decisions. Ann Neurol
      2017;82:686-696.

PMID- 29023966
TI  - Genotoxicity of airborne PM2.5 assessed by salmonella and comet assays in five
      cities of the Emilia-Romagna (Italy) mutagenicity monitoring network.
AB  - Airborne particulate matter (PM) has long been recognized as a potential health
      hazard and in 2013 was classified as carcinogenic to humans by the International
      Agency for Research on Cancer. In this study we evaluate and compare mutagenic
      and genotoxic potencies of PM2.5 collected in three seasons, from 2012 to 2015,
      in five Italian cities. Mutagenicity was evaluated through the Ames test on TA98
      and TA100 strains and, for the measurement of PM clastogenicity, Comet assay was
      carried out on cultured human lung cells (A549). Organic matter, extracted from
      urban particulate matter, was also characterized for polycyclic aromatic
      hydrocarbons (PAHs) and their derivatives content. Samples collected in the
      colder seasons show the presence of both base pair substitution and frameshift
      mutagens, with enhanced mutagenic response in the absence of enzyme activation.
      The highest DNA damage detected with the Comet assay was induced by winter
      extracts, but different from Salmonella, the relative increase per cubic meter in
      comet tail for November samples was comparable to July ones. Comparing
      mutagenicity and genotoxicity with chemical concentrations we found that data
      from the Salmonella assay correlate with mass concentration and, to a lesser
      extent, with PAHs, but no association was found with their derivatives, whereas
      DNA damage correlate only with PAHs measured at one site. These findings
      demonstrate that to assess the mutagenicity and genotoxicity of complex mixtures
      it's necessary to use bioassays and that the chemical analysis of pollutants does
      not take into account the possible inhibitory or synergic effects of exposure.
      Environ. Mol. Mutagen. 58:719-729, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 29023967
TI  - Copper toxicity and date palm (Phoenix dactylifera) seedling tolerance:
      Monitoring of related biomarkers.
AB  - Date palm (Phoenix dactylifera) seeds were exposed to different copper (Cu)
      solutions to examine plant stress responses. Low Cu concentrations (0.02 and 0.2
      mM) caused an increase of seed germination, whereas higher Cu amounts (2 mM)
      significantly inhibited seed germination, delayed hypocotyl elongation, increased
      seedling mortality, and reduced the germination index by more than 90%. Metal
      related toxicity symptoms appeared after 15 d of 2 mM of Cu exposure. Biochemical
      activities such as amylase activity and redox balance elements were examined to
      study the relationship between external Cu amount and internal plant response.
      The present study showed that amylolytic activity was dose- and time-dependent.
      Likewise, H2 O2 production increased after exposure to Cu, which was correlated
      with thiobarbituric acid reactive substance (TBARS) accumulation. Furthermore at
      low Cu concentrations, superoxide dismutase (SOD) and catalase (CAT) activities
      increased, suggesting that date palm seed stimulated its metal homeostasis
      networks. However, the highest cupric ion amounts increased cell oxidant
      accumulation and reduced enzyme production. Gene expression level measures of P.
      dactylifera phytochelatin synthase (Pdpcs) and P. dactylifera metallothionein
      (Pdmt) encoding genes have been carried out to investigate the implication of
      PdPCS and PdMT proteins in Cu homeostasis and/or its sequestration. Phoenix
      dactylifera metallothionein induction reached a peak after 30 d of exposure to
      0.2 mM of Cu. However, it was down-regulated in plants exposed to higher Cu
      concentrations. In the same conditions, Pdpcs was overexpressed during 1 mo of
      exposure before it decreased thereafter. These observations provide a new insight
      into date palm cell response to Cu, a metal that can be toxic but that is also an
      essential element. Environ Toxicol Chem 2018;37:797-806. (c) 2017 SETAC.

PMID- 29023968
TI  - Pregnant Metaphors and Surrogate Meanings: Bringing the Ethnography of Pregnancy
      and Surrogacy into Conversation in Israel and Beyond.
AB  - This article explores the way that surrogacy and normal pregnancy share cultural
      assumptions about pregnancy. Through a juxtaposition of our ethnographic studies
      of two groups of Jewish-Israeli women-women who have undergone "normal," low-risk
      pregnancies and women who have given birth as gestational surrogates-we argue
      that surrogacy and pregnancy emerge as potent metaphors for one another. Both
      pregnant women and surrogates divided their bodies into two separate realms:
      fetus and maternal pregnant body. Both trivialized the effect of gestational
      influence on fetal health, making the fetus seem detached from gestational
      capacities of the mother. We argue for closer scrutiny of the way local cultural
      priorities and experiences of pregnancy shape surrogacy and for bringing the
      scholarship on pregnancy and on surrogacy into deeper conversation.

PMID- 29023969
TI  - Calculating potential error in sodium MRI with respect to the analysis of small
      objects.
AB  - PURPOSE: To facilitate correct interpretation of sodium MRI measurements,
      calculation of error with respect to rapid signal decay is introduced and
      combined with that of spatially correlated noise to assess volume-of-interest
      (VOI) 23 Na signal measurement inaccuracies, particularly for small objects.
      METHODS: Noise and signal decay-related error calculations were verified using
      twisted projection imaging and a specially designed phantom with different sized
      spheres of constant elevated sodium concentration. As a demonstration, lesion
      signal measurement variation (5 multiple sclerosis participants) was compared
      with that predicted from calculation. RESULTS: Both theory and phantom experiment
      showed that VOI signal measurement in a large 10-mL, 314-voxel sphere was 20%
      less than expected on account of point-spread-function smearing when the VOI was
      drawn to include the full sphere. Volume-of-interest contraction reduced this
      error but increased noise-related error. Errors were even greater for smaller
      spheres (40-60% less than expected for a 0.35-mL, 11-voxel sphere). Image
      intensity VOI measurements varied and increased with multiple sclerosis lesion
      size in a manner similar to that predicted from theory. Correlation suggests
      large underestimation of 23 Na signal in small lesions. CONCLUSIONS: Acquisition
      specific measurement error calculation aids 23 Na MRI data analysis and
      highlights the limitations of current low-resolution methodologies. Magn Reson
      Med 79:2968-2977, 2018. (c) 2017 International Society for Magnetic Resonance in
      Medicine.

PMID- 29023971
TI  - A Fluid Liquid-Crystal Material with Highly Polar Order.
AB  - An anomalously large dielectric permittivity of ~104 is found in the mesophase
      temperature range (MP phase) wherein high fluidity is observed for a liquid
      crystal compound having a 1,3-dioxane unit in the mesogenic core (DIO). In this
      temperature range, no sharp X-ray diffraction peak is observed at both small and
      wide Bragg angles, similar to that for a nematic phase; however, an inhomogeneous
      sandy texture or broken Schlieren one is observed via polarizing optical
      microscopy, unlike that for a conventional nematic phase. DIO exhibits
      polarization switching with a large polarization value, i.e., P = 4.4 uC cm-2 ,
      and a parallelogram-shaped polarization-electric field hysteresis loop in the MP
      phase. The inhomogeneously aligned DIO in the absence of an electric field adopts
      a uniform orientation along an applied electric field when field-induced
      polarization switching occurs. Furthermore, sufficiently larger second-harmonic
      generation is observed for DIO in the MP phase. Second-harmonic-generation
      interferometry clearly shows that the sense of polarization is inverted when the
      +/- sign of the applied electric field in MP is reversed. These results suggest
      that a unidirectional, ferroelectric-like parallel polar arrangement of the
      molecules is generated along the director in the MP phase.

PMID- 29023972
TI  - Covariate adjustment using propensity scores for dependent censoring problems in
      the accelerated failure time model.
AB  - In many medical studies, estimation of the association between treatment and
      outcome of interest is often of primary scientific interest. Standard methods for
      its evaluation in survival analysis typically require the assumption of
      independent censoring. This assumption might be invalid in many medical studies,
      where the presence of dependent censoring leads to difficulties in analyzing
      covariate effects on disease outcomes. This data structure is called
      "semicompeting risks data," for which many authors have proposed an artificial
      censoring technique. However, confounders with large variability may lead to
      excessive artificial censoring, which subsequently results in numerically
      unstable estimation. In this paper, we propose a strategy for weighted estimation
      of the associations in the accelerated failure time model. Weights are based on
      propensity score modeling of the treatment conditional on confounder variables.
      This novel application of propensity scores avoids excess artificial censoring
      caused by the confounders and simplifies computation. Monte Carlo simulation
      studies and application to AIDS and cancer research are used to illustrate the
      methodology.

PMID- 29023970
TI  - Phenotype validation in electronic health records based genetic association
      studies.
AB  - The linkage between electronic health records (EHRs) and genotype data makes it
      plausible to study the genetic susceptibility of a wide range of disease
      phenotypes. Despite that EHR-derived phenotype data are subjected to
      misclassification, it has been shown useful for discovering susceptible genes,
      particularly in the setting of phenome-wide association studies (PheWAS). It is
      essential to characterize discovered associations using gold standard phenotype
      data by chart review. In this work, we propose a genotype stratified case-control
      sampling strategy to select subjects for phenotype validation. We develop a
      closed-form maximum-likelihood estimator for the odds ratio parameters and a
      score statistic for testing genetic association using the combined validated and
      error-prone EHR-derived phenotype data, and assess the extent of power
      improvement provided by this approach. Compared with case-control sampling based
      only on EHR-derived phenotype data, our genotype stratified strategy maintains
      nominal type I error rates, and result in higher power for detecting
      associations. It also corrects the bias in the odds ratio parameter estimates,
      and reduces the corresponding variance especially when the minor allele frequency
      is small.

PMID- 29023973
TI  - High-resolution mass spectrometry of skin mucus for monitoring physiological
      impacts and contaminant biotransformation products in fathead minnows exposed to
      wastewater effluent.
AB  - High-resolution mass spectrometry is advantageous for monitoring physiological
      impacts and contaminant biotransformation products in fish exposed to complex
      wastewater effluent. We evaluated this technique using skin mucus from male and
      female fathead minnows (Pimephales promelas) exposed to control water or treated
      wastewater effluent at 5, 20, and 100% levels for 21 d, using an on-site, flow
      through system providing real-time exposure. Both sex-specific and non-sex
      specific responses were observed in the mucus metabolome, the latter suggesting
      the induction of general compensatory pathways for xenobiotic exposures.
      Altogether, 85 statistically significant treatment-dependent metabolite changes
      were observed out of the 310 total endogenous metabolites that were detected (156
      of the 310 were annotated). Partial least squares-regression models revealed
      strong covariances between the mucus metabolomes and up-regulated hepatic
      messenger ribonucleic acid (mRNA) transcripts reported previously for these same
      fish. These regression models suggest that mucus metabolomic changes reflected,
      in part, processes by which the fish biotransformed xenobiotics in the effluent.
      In keeping with this observation, we detected a phase II transformation product
      of bisphenol A in the skin mucus of male fish. Collectively, these findings
      demonstrate the utility of mucus as a minimally invasive matrix for
      simultaneously assessing exposures and effects of environmentally relevant
      mixtures of contaminants. Environ Toxicol Chem 2018;37:788-796. Published 2017
      Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work
      and, as such, is in the public domain in the United States of America.

PMID- 29023974
TI  - Diabetes-related major lower limb amputation incidence is strongly related to
      diabetic foot service provision and improves with enhancement of services: peer
      review of the South-West of England.
AB  - AIMS: To investigate the relationship between high diabetes-related lower limb
      amputation incidence and foot care services in the South-West region of England.
      METHODS: The introduction of 10 key elements of foot care service provision in
      one area of the South-West resulted in stabilization of foot ulcer incidence and
      sustained reduction in amputation incidence from 2007. Services introduced
      included administrative support, standardized general practice foot screening,
      improved community podiatry staffing, hospital multidisciplinary foot clinics,
      effective care pathways, availability of an orthotist and audit. Peer reviews of
      the region's diabetes foot care services were undertaken to assess delivery of
      these service provisions and compare this with major amputation incidence in
      other regions with data provided by Yorkshire and Humber Public Health
      Observatory Hospital Episode Statistics. Recommendations were made to improve
      service provision. In 2015 changes in service provision and amputation incidence
      were reviewed. RESULTS: Initial reviews in 2013 showed that the 3-year diabetes
      related major amputation incidence correlated inversely with adequate delivery of
      diabetes foot care services (P=0.0024, adjusted R2 =0.51). Repeat reviews in 2015
      found that two or more foot care service improvements were reported by six
      diabetes foot care providers, with improvement in outcomes. The negative
      relationship between major amputation incidence and service provision remained
      strong both in the period 2012-2015 and in the year 2015 only (P <=0.0012,
      adjusted R2 =0.56, and P= 0.0005, R2 =0.62, respectively). CONCLUSIONS: Major
      diabetes-related lower limb amputation incidence is significantly inversely
      correlated with foot care services provision. Introduction of more effective
      service provision resulted in significant reductions in major amputation
      incidence within 2 years. Failure to improve unsatisfactory service provision
      resulted in continued high amputation incidence.

PMID- 29023975
TI  - Motion robust high resolution 3D free-breathing pulmonary MRI using dynamic 3D
      image self-navigator.
AB  - PURPOSE: To achieve motion robust high resolution 3D free-breathing pulmonary MRI
      utilizing a novel dynamic 3D image navigator derived directly from imaging data.
      METHODS: Five-minute free-breathing scans were acquired with a 3D ultrashort echo
      time (UTE) sequence with 1.25 mm isotropic resolution. From this data, dynamic 3D
      self-navigating images were reconstructed under locally low rank (LLR)
      constraints and used for motion compensation with one of two methods: a soft
      gating technique to penalize the respiratory motion induced data inconsistency,
      and a respiratory motion-resolved technique to provide images of all respiratory
      motion states. RESULTS: Respiratory motion estimation derived from the proposed
      dynamic 3D self-navigator of 7.5 mm isotropic reconstruction resolution and a
      temporal resolution of 300 ms was successful for estimating complex respiratory
      motion patterns. This estimation improved image quality compared to respiratory
      belt and DC-based navigators. Respiratory motion compensation with soft-gating
      and respiratory motion-resolved techniques provided good image quality from
      highly undersampled data in volunteers and clinical patients. CONCLUSION: An
      optimized 3D UTE sequence combined with the proposed reconstruction methods can
      provide high-resolution motion robust pulmonary MRI. Feasibility was shown in
      patients who had irregular breathing patterns in which our approach could depict
      clinically relevant pulmonary pathologies. Magn Reson Med 79:2954-2967, 2018. (c)
      2017 International Society for Magnetic Resonance in Medicine.

PMID- 29023976
TI  - Peripheral nerve involvement in multiple sclerosis: Demonstration by magnetic
      resonance neurography.
AB  - OBJECTIVE: To detect and quantify peripheral nerve lesions in multiple sclerosis
      (MS) by magnetic resonance neurography (MRN). METHODS: Thirty-six patients
      diagnosed with MS based on the 2010 McDonald criteria (34 with the relapsing
      remitting form, 2 with clinically isolated syndrome) with and without disease
      modifying treatment were compared to 35 healthy age-/sex-matched volunteers. All
      patients underwent detailed neurological and electrophysiological examinations.
      Three Tesla MRN with large anatomical coverage of both legs and the lumbosacral
      plexus was performed by using 2-dimensional (2D) fat-saturated, T2-weighted (T2w)
      and dual echo turbo spin echo sequences as well as a 3D T2-weighted, fat
      saturated SPACE sequence. Besides qualitative visual nerve assessment, a T2w
      signal quantification was performed by calculation of proton spin density and T2
      relaxation time. Nerve diameter was measured as a morphometric criterion.
      RESULTS: T2w hyperintense nerve lesions were detectable in all MS patients, with
      a mean lesion number at thigh level of 151.5 +/- 5.7 versus 19.1 +/- 2.4 in
      controls (p < 0.0001). Nerve proton spin density was higher in MS
      (tibial/peroneal: 371.8 +/- 7.7/368.9 +/- 8.2) versus controls (tibial/peroneal:
      266.0 +/- 11.0/276.8 +/- 9.7, p < 0.0001). In contrast, T2 relaxation time was
      significantly higher in controls (tibial/peroneal: 82.0 +/- 2.1/78.3 +/- 1.7)
      versus MS (tibial/peroneal: 64.3 +/- 1.0/61.2 +/- 0.9, p < 0.0001). Proximal
      tibial and peroneal nerve caliber was higher in MS (tibial: 52.4 +/- 2.1mm2 ,
      peroneal: 25.4 +/- 1.3mm2 ) versus controls (tibial: 45.2 +/- 1.4mm2 , p <
      0.0015; peroneal: 21.3 +/- 0.7mm2 , p = 0.0049). INTERPRETATION: Peripheral nerve
      lesions could be visualized and quantified in MS in vivo by high-resolution MRN.
      Lesions are defined by an increase of proton spin density and a decrease of T2
      relaxation time, indicating changes in the microstructural organization of the
      extracellular matrix in peripheral nerve tissue in MS. By showing involvement of
      the peripheral nervous system in MS, this proof-of-concept study may offer new
      insights into the pathophysiology and treatment of MS. Ann Neurol 2017;82:676
      685.

PMID- 29023977
TI  - Program expansion of a day hospital dedicated to manage sickle cell pain.

PMID- 29023978
TI  - Weight gain after treatment of Graves' disease in children.
AB  - OBJECTIVE: The frequency of and risk factors for weight gain in children treated
      for Graves' disease have not been described. We evaluated change in BMI-Z score
      and predictors of weight gain in this population. DESIGN: Retrospective review of
      data from January 2000 to July 2011. PATIENTS: Two hundred and twenty two
      children and adolescents with Graves' disease (ages 2-18 years) evaluated
      following radioactive iodine administration (RAI); (n = 101), thyroidectomy (n =
      9) and initiation of medical therapy (n = 112). MEASUREMENTS: Changes in body
      mass index Z score over 12 months (DeltaBMI-Z0-12 ). RESULTS: All treatment
      groups in each gender and race increased BMI-Z (median DeltaBMI-Z0-12 was
      positive). T3 levels following RAI (P = .04) and weight lost at the time of
      administration (P = .02) in the RAI group and free T4 levels in the medical
      therapy group (P = .03) were positively correlated with DeltaBMI-Z0-12 . Race was
      a significant predictor only in the medical therapy group (P = .01). Age
      negatively correlated with DeltaBMI-Z0-12 in both the RAI (P < .001) and medical
      therapy groups (P = .003). Gender, maximum TSH in the 12 months after RAI and
      initial dose of LT4 replacement did not correlate with DeltaBMI-Z0-12 . The
      prevalence of overweight and obesity in our cohort was similar to US children.
      CONCLUSIONS: Weight gain during treatment for Graves' disease is common in
      children, and many children become overweight or obese during treatment. Risk
      factors include greater degree of hyperthyroidism at presentation and time of RAI
      and younger age. Weight lost upon presentation may also predict greater weight
      gain. Control of subsequent hypothyroidism does not appear to affect weight gain.

PMID- 29023979
TI  - Sox8 and Sox10 jointly maintain myelin gene expression in oligodendrocytes.
AB  - In Schwann cells of the vertebrate peripheral nervous system, induction of
      myelination and myelin maintenance both depend on the HMG-domain-containing
      transcription factor Sox10. In oligodendrocytes of the central nervous system,
      Sox10 is also essential for the induction of myelination. Its role in late phases
      of myelination and myelin maintenance has not been studied so far. Here, we show
      that these processes are largely unaffected in mice that lack Sox10 in mature
      oligodendrocytes. As Sox10 is co-expressed with the related Sox8, we also
      analyzed oligodendrocytes and myelination in Sox8-deficient mice. Again, we could
      not detect any major abnormalities. Expression of many myelin genes was only
      modestly reduced in both mouse mutants. Dramatic reductions in expression levels
      and phenotypic disturbances became only apparent once Sox8 and Sox10 were both
      absent. This argues that Sox8 and Sox10 are jointly required for myelin
      maintenance and impact myelin gene expression. One direct target gene of both Sox
      proteins is the late myelin gene Mog. Our results point to at least partial
      functional redundancy between both related Sox proteins in mature
      oligodendrocytes and are the first report of a substantial function of Sox8 in
      the oligodendroglial lineage.

PMID- 29023980
TI  - Agminated segmental plaque-type blue nevus associated with hypertrichosis and
      soft tissue hypertrophy: Report of a case and review of the literature.
AB  - Blue nevi are common skin neoplasms that typically present as asymptomatic
      solitary papules, although they may rarely occur in an agminated configuration.
      We describe a case of agminated blue nevus in a segmental facial distribution
      associated with soft tissue hypertrophy and hypertrichosis in a 16-year-old boy
      and present a review of the literature. Although they are generally considered to
      be benign, concurrent soft tissue changes occurring within an agminated blue
      nevus should be investigated thoroughly to exclude alternate diagnoses.

PMID- 29023981
TI  - 4-bp insertion/deletion (rs3783553) polymorphism within the 3'UTR of IL1A
      contributes to the risk of prostate cancer in a sample of Iranian population.
AB  - Growing evidence demonstrated the presence of an association between IL1A
      rs3783553 polymorphism and the risk of various cancers. We aimed to evaluate
      whether the 4-bp insertion/deletion polymorphism (rs3783553) within the 3'
      untranslated region (3'UTRs) of IL1A was associated to the risk of prostate
      cancer (PCa) in a sample of Iranian population. A case-control study, including
      150 prostate cancer patients and 155 healthy men, was done to examine the
      possible association between IL1A 4-bp ins/del polymorphism and PCa risk in a
      sample of southeast Iranian population. Mismatched polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) was designed for genotyping
      the studied variant. Our findings showed that 4-bp ins/del polymorphism
      significantly increased the risk of PCa in codominant, recessive and allelic
      inheritance model. We also evaluated the association between the IL1A 4-bp
      ins/del polymorphism and clinicopathological characteristics of the patients, and
      found a significant association between 4-bp ins/del variant and stage,
      perineural invasion and surgical margin of tumor samples. Bioinformatics analysis
      revealed that the ins/del variant affected the IL1A mRNA stability leading to a
      structural shift in IL1A mRNA and has-miR-125a-3p hybrid. In conclusion, our
      findings proposed an association between IL1A 4-bp ins/del polymorphism and PCa
      risk. Additional studies with enlarged sample size and diverse ethnicities are
      required to validate our finding.

PMID- 29023982
TI  - MEDI+0: Morphology enabled dipole inversion with automatic uniform cerebrospinal
      fluid zero reference for quantitative susceptibility mapping.
AB  - PURPOSE: To develop a quantitative susceptibility mapping (QSM) method with a
      consistent zero reference using minimal variation in cerebrospinal fluid (CSF)
      susceptibility. THEORY AND METHODS: The ventricular CSF was automatically
      segmented on the R2* map. An L2 -regularization was used to enforce CSF
      susceptibility homogeneity within the segmented region, with the averaged CSF
      susceptibility as the zero reference. This regularization for CSF homogeneity was
      added to the model used in a prior QSM method (morphology enabled dipole
      inversion [MEDI]). Therefore, the proposed method was referred to as MEDI+0 and
      compared with MEDI in a numerical simulation, in multiple sclerosis (MS) lesions,
      and in a reproducibility study in healthy subjects. RESULTS: In both the
      numerical simulations and in vivo experiments, MEDI+0 not only decreased the
      susceptibility variation within the ventricular CSF, but also suppressed the
      artifact near the lateral ventricles. In the simulation, MEDI+0 also provided
      more accurate quantification compared to MEDI in the globus pallidus, substantia
      nigra, corpus callosum, and internal capsule. MEDI+0 measurements of MS lesion
      susceptibility were in good agreement with those obtained by MEDI. Finally, both
      MEDI+0 and MEDI showed good and similar intrasubject reproducibility. CONCLUSION:
      QSM with a minimal variation in ventricular CSF is viable to provide a consistent
      zero reference while improving image quality. Magn Reson Med 79:2795-2803, 2018.
      (c) 2017 International Society for Magnetic Resonance in Medicine.

PMID- 29023984
TI  - Partial to complete abrogation of the subepithelial macrophage barrier against
      the gut microbiota in patients with ulcerative colitis and Crohn's colitis.
AB  - AIMS: The integrity of the band of indigenous macrophages in the subepithelial
      layer of the lamina propria (SLP) is crucial in preventing the commensal gut
      microbiota from attacking the host. The breakdown of the SLP macrophage barrier
      results in microbiota inflow and improper immune responses; this might lead to
      inflammatory bowel disease (IBD). During inflammation, the SLP macrophage barrier
      is reinforced by inflammation-elicited macrophages (IEMs), which are derived from
      blood-circulating monocytes. The aim was to explore the characteristics of the
      SLP macrophage band in a cohort of biopsies without inflammation, in patients
      with ulcerative colitis in remission (UCre), and in patients with right-sided
      Crohn's colitis (RCC). METHODS AND RESULTS: Endoscopic biopsies were taken from
      endoscopically normal descending colon in 247 patients; 80 with IBD (27 UCre and
      53 RCC), and 167 without IBD [90 had colonic diarrhoea, 63 were enrolled in a
      colorectal cancer (CRC) surveillance programme, seven had microscopic colitis in
      remission, and seven had miscellaneous colonic ailments]. Sections showed no
      inflammatory changes; they were immunostained with CD68. Among patients with UCre
      and RCC, the SLP band of CD68+ macrophages was fragmented or minute in 59%
      (47/80) and negative in 9% (7/80). In contrast, only 31% (51/167) of the biopsies
      from control patients had a fragmented/minute SLP band of CD68+ macrophages, and
      none had a negative SLP band of CD68+ macrophages (IBD versus controls, P <
      0.05). CONCLUSIONS: The finding that the SLP macrophage barrier was fragmented to
      totally abrogated in UCre and RCC patients suggests a longlasting defect in the
      SLP CD68+ macrophage barrier in these patients. The lack of ongoing inflammation
      in colonic biopsies should rule out the participation of bone marrow-derived IEMs
      in the abrogation of the SLP macrophage barrier reported here.

PMID- 29023983
TI  - Age, vascular health, and Alzheimer disease biomarkers in an elderly sample.
AB  - OBJECTIVE: To investigate the associations between age, vascular health, and
      Alzheimer disease (AD) imaging biomarkers in an elderly sample. METHODS: We
      identified 430 individuals along the cognitive continuum aged >60 years with
      amyloid positron emission tomography (PET), tau PET, and magnetic resonance
      imaging (MRI) scans from the population-based Mayo Clinic Study of Aging. A
      subset of 329 individuals had fluorodeoxyglucose (FDG) PET. We ascertained
      presently existing cardiovascular and metabolic conditions (CMC) from health care
      records and used the summation of presence/absence of hypertension,
      hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart
      failure, diabetes mellitus, and stroke as a surrogate for vascular health. We
      used global amyloid from Pittsburgh compound B PET, entorhinal cortex tau uptake
      (ERC-tau) from tau-PET, and neurodegeneration in AD signature regions from MRI
      and FDG-PET as surrogates for AD pathophysiology. We dichotomized participants
      into CMC = 0 (CMC- ) versus CMC > 0 (CMC+ ) and tested for age-adjusted group
      differences in AD biomarkers. Using structural equation models (SEMs), we
      assessed the impact of vascular health on AD biomarker cascade (amyloid leads to
      tau leads to neurodegeneration) after considering the direct and indirect age,
      sex, and apolipoprotein E effects. RESULTS: CMC+ participants had significantly
      greater neurodegeneration than CMC- participants but did not differ by amyloid or
      ERC-tau. The SEMs showed that (1) vascular health had a significant direct and
      indirect impact on neurodegeneration but not on amyloid; and (2) vascular health,
      specifically the presence of hyperlipidemia, had a significant direct impact on
      ERC-tau. INTERPRETATION: Vascular health had quantifiably greater impact on
      neurodegeneration in AD regions than on amyloid deposition. Longitudinal studies
      are warranted to clarify the relationship between tau deposition and vascular
      health. Ann Neurol 2017;82:706-718.

PMID- 29023986
TI  - Evaluation of short- and long-term efficacy of chemoradiotherapy for advanced
      cervical cancer using HSP70 protein combined with multimodal MRI.
AB  - This study aims to evaluate the efficacy of chemoradiotherapy for advanced
      cervical cancer using heat shock protein 70 (HSP70) combined with multimodal MRI.
      The protein expressions of HSP70 in biopsy specimens obtained from 101 patients
      with cervical cancer were detected by immunohistochemistry. Plain MRI scan, DWI,
      DCE-MR, and MRS were performed before and after a period of 6 months of
      chemoradiotherapy. All patients were assigned into the complete response (CR) and
      partial response (PR) groups. HSP70 protein expression, tumor diameter, and tumor
      volume were lower in the CR group than in the PR group. The rate of tumor
      shrinkage, relative positive enhancement integral (rPEI), relative maximum slope
      of decrease (rMSD), relative signal enhancement ratio at 60 s (rSER60 ) and
      maximum SER (rSERmax ), mean apparent diffusion coefficient (ADCmean ) and
      minimum ADC value (ADCmin ) values in the CR group were higher than those in the
      PR group. Tumor diameter and volume, rSER15 and rSER30 were reduced after
      chemoradiotherapy, while rMSD, rSERmax , time to peak (TTP), ADCmean and ADCmin
      were higher after the treatment. The receiver operating characteristic (ROC)
      curves indicated that HSP70 expression, tumor diameter, rPEI, ADCmean and Cho
      peak showed the better chemoradiotherapy efficacy. Our data demonstrates that
      HSP70 protein combined with multimodal MRI may accurately evaluate the
      chemoradiotherapy efficacy of patients with advanced cervical cancer. The
      recurrence of cervical cancer significantly decreased in patients with negative
      expression of HSP70 and HSP70 protein detection provides potential therapy for
      the prevention, diagnosis, and prognosis of cervical cancer.

PMID- 29023985
TI  - Interaction between calcitonin gene-related peptide-immunoreactive neurons and
      satellite cells via P2Y12 R in the trigeminal ganglion is involved in neuropathic
      tongue pain in rats.
AB  - The P2Y12 receptor expressed in satellite cells of the trigeminal ganglion is
      thought to contribute to neuropathic pain. The functional interaction between
      neurons and satellite cells via P2Y12 receptors and phosphorylated extracellular
      signal-regulated kinase 1/2 (pERK1/2) underlying neuropathic pain in the tongue
      was evaluated in this study. Expression of P2Y12 receptor was enhanced in pERK1/2
      immunoreactive cells encircling trigeminal ganglion neurons after lingual nerve
      crush. The administration to lingual nerve crush rats of a selective P2Y12
      receptor antagonist, MRS2395, attenuated tongue hypersensitivity to mechanical
      and heat stimulation and suppressed the increase in the relative numbers of
      calcitonin gene-related peptide (CGRP)-immunoreactive neurons and neurons
      encircled by pERK1/2-immunoreactive cells. Administration of the P2Y1,12,13
      receptor agonist, 2-(methylthio)adenosine 5'-diphosphate trisodium salt hydrate
      (2-MeSADP), to naive rats induced neuropathic pain in the tongue, as in lingual
      nerve crush rats. Co-administration of 2-MeSADP + MRS2395 to naive rats did not
      result in hypersensitivity of the tongue. The relative number of CGRP
      immunoreactive neurons increased following this co-administration, but to a
      lesser degree than observed in 2-MeSADP-administrated naive rats, and the
      relative number of neurons encircled by pERK1/2-immunoreactive cells did not
      change. These results suggest that the interaction between activated satellite
      cells and CGRP-immunoreactive neurons via P2Y12 receptors contributes to
      neuropathic pain in the tongue associated with lingual nerve injury.

PMID- 29023987
TI  - Prevalence of delusions in drug-naive Alzheimer disease patients: A meta
      analysis.
AB  - INTRODUCTION: Neuropsychiatric symptoms (NPS) are common at all stages of
      Alzheimer disease (AD). Delusions in AD are associated with negative clinical
      consequences and may signal rapid disease progression. Hence, we sought to
      determine the prevalence of delusions in drug-naive (no cholinesterase inhibitor
      or neuroleptic medications) AD patients. METHODS: In this meta-analysis, a search
      of the EMBASE, MEDLINE, and PsycINFO databases was performed. We selected studies
      reporting delusion prevalence measured by the Neuropsychiatric Inventory (NPI) in
      drug-naive AD patients. An aggregate delusion event rate with 95% confidence
      interval (CI) was calculated. The I2 statistic was used to assess the magnitude
      of between-study heterogeneity. Single variable meta-regressions allowed
      examination of the effect of moderating factors and heterogeneity. Quantitative
      measures were used to appraise for publication bias. RESULTS: We identified 6
      studies with 591 participants allowing calculation of the aggregate delusional
      prevalence rate. Irrespective of dementia severity, the aggregate event rate for
      delusions was 29.1% (95% CI: 20-41%; I2  = 84.59). No publication bias was
      observed. CONCLUSION: This meta-analysis calculates a 29.1% prevalence rate of
      delusions in AD patients. There is a trend towards increasing delusion prevalence
      in concordance with increasing severity of dementia. Given delusions are
      associated with poorer outcomes, the obtained prevalence should motivate
      clinicians to screen carefully for delusions. Current literature limitations
      warrant future studies, with sub-analyses on dementia severity, and other
      neurobiological factors known to influence the presence of delusions.

PMID- 29023988
TI  - Molecular dynamics simulation, binding free energy calculation and unbinding
      pathway analysis on selectivity difference between FKBP51 and FKBP52: Insight
      into the molecular mechanism of isoform selectivity.
AB  - As co-chaperones of the 90-kDa heat shock protein(HSP90), FK506 binding protein
      51 (FKBP51) and FK506 binding protein 52 (FKBP52) modulate the maturation of
      steroid hormone receptor through their specific FK1 domains (FKBP12-like domain
      1). The inhibitors targeting FK1 domains are potential therapies for endocrine
      related physiological disorders. However, the structural conservation of the FK1
      domains between FKBP51 and FKBP52 make it difficult to obtain satisfactory
      selectivity in FK506-based drug design. Fortunately, a series of iFit ligands
      synthesized by Hausch et al exhibited excellent selectivity for FKBP51, providing
      new opportunity for design selective inhibitors. We performed molecular dynamics
      simulation, binding free energy calculation and unbinding pathway analysis to
      reveal selective mechanism for the inhibitor iFit4 binding with FKBP51 and
      FKBP52. The conformational stability evaluation of the "Phe67-in" and "Phe67-out"
      states implies that FKBP51 and FKBP52 have different preferences for "Phe67-in"
      and "Phe67-out" states, which we suggest as the determinant factor for the
      selectivity for FKBP51. The binding free energy calculations demonstrate that
      nonpolar interaction is favorable for the inhibitors binding, while the polar
      interaction and entropy contribution are adverse for the inhibitors binding.
      According to the results from binding free energy decomposition, the
      electrostatic difference of residue 85 causes the most significant thermodynamics
      effects on the binding of iFit4 to FKBP51 and FKBP52. Furthermore, the importance
      of substructure units on iFit4 were further evaluated by unbinding pathway
      analysis and residue-residue contact analysis between iFit4 and the proteins. The
      results will provide new clues for the design of selective inhibitors for FKBP51.

PMID- 29023990
TI  - Selection of composite binary endpoints in clinical trials.
AB  - The choice of a primary endpoint is an important issue when designing a clinical
      trial. It is common to use composite endpoints as a primary endpoint because it
      increases the number of observed events, captures more information and is
      expected to increase the power. However, combining events that have no similar
      clinical importance and have different treatment effects makes the interpretation
      of the results cumbersome and might reduce the power of the corresponding tests.
      Gomez and Lagakos proposed the ARE (asymptotic relative efficiency) method to
      choose between a composite or one of its components as primary endpoint comparing
      the efficacy of a treatment based on the times to each of these endpoints. The
      aim of this paper is to expand the ARE method to binary endpoints. We show that
      the ARE method depends on six parameters including the degree of association
      between components, event proportion, and effect of therapy given by the
      corresponding odds ratio of the single endpoints. A case study is presented to
      illustrate the methodology. We conclude with efficient guidelines for discerning
      which could be the best suited primary endpoint given anticipated parameters.

PMID- 29023989
TI  - Impact of contact lens material and design on the ocular surface.
AB  - BACKGROUND: To evaluate the impact on the ocular surface of a daily disposable
      hydrogel contact lens with high water content compared with two silicone hydrogel
      daily disposable lenses of lower water content. METHODS: The hydrogel lens
      assessed was made from nesofilcon A and the silicone hydrogel lenses were made of
      delefilcon A and stenfilcon A. Contact lens thickness was measured to assess
      material stability during daily wear, and ocular surface parameters such as tear
      film osmolarity, tear meniscus area and central corneal thickness were also
      assessed. Optical quality was analysed for all cases by means of wavefront
      aberrometry. RESULTS: The nesofilcon A was shown to be the thinnest lens (p <
      0.001), while no differences in lens thickness were found between the two
      silicone hydrogel lenses (p = 0.495). No significant differences were found in
      tear film osmolarity, tear meniscus area, central corneal thickness or corneal
      aberrations, either as a function of the lens measured or time of use (p > 0.05).
      CONCLUSION: In spite of having the thinnest lens and the highest water content,
      the hydrogel does not significantly impact on tear film and corneal swelling
      after one day of use in first-time wearers.

PMID- 29023991
TI  - Correlation of head-up tilt table test time interval with future risk of
      recurrent syncope.
AB  - BACKGROUND: Head-up tilt table test (HUTT) is widely used for the investigation
      of syncope and presyncope. Time required for positive response has a probable
      relationship to the sensitivity of neural reflex mechanism underlying syncope.
      METHODS: We evaluated patients with history of syncope. Group A included patients
      with recurrent syncope defined as two or more episodes of syncope and group B
      included those with one episode of syncope. Time required for the test to become
      positive in both the groups was analyzed. Patients with positive HUTT were
      followed for 1 year. RESULTS: Of 80 patients, 68 eligible study patients were
      divided into group A (32.35%) and group B (67.65%). HUTT was positive in 41
      patients (positivity rate  =  60.29%). Positivity rate was 100% in group A and
      41.3% in group B. Median time interval for positive response in groups A and B
      were 12.5 and 30.0 minutes, respectively. An inverse association was found
      between recurrent syncope and time interval for positive response (R  =  - 0.282,
      P  =  0.002). Time interval of less than 19.5 minutes for positive response had
      94.5% sensitivity and 97.89% specificity for recurrent syncope. On follow-up,
      positive association was found between time interval for positive response less
      than 19.5 minutes and future recurrence of syncope (odds ratio  =  22.75, 95%
      confidence interval  =  4.37-118.34, P  =  0.000). CONCLUSION: HUTT time interval
      of less than 19.5 minutes for positive response predicted future recurrence of
      syncope. Hence, it may serve as an important predictor of future recurrence of
      syncope.

PMID- 29023992
TI  - Therapy related-chronic myelomonocytic leukemia (CMML): Molecular, cytogenetic,
      and clinical distinctions from de novo CMML.
AB  - Therapy related myeloid neoplasms (t-MN) including therapy related
      myelodysplastic syndromes (t-MDS) and acute myeloid leukemia (t-AML) are
      associated with aggressive disease biologies and poor outcomes. In this large (n
      = 497) and informative (inclusive of molecular and cytogenetic information)
      chronic myelomonocytic leukemia (CMML) patient cohort, we demonstrate key
      biological insights and an independent prognostic impact for t-CMML. T-CMML was
      diagnosed in 9% of patients and occurred approximately 7 years after exposure to
      prior chemotherapy and/or radiation therapy. In comparison to de novo CMML, t
      CMML patients had higher LDH levels, higher frequency of karyotypic abnormalities
      and had higher risk cytogenetic stratification. There were no differences in the
      distribution of gene mutations and unlike t-MDS/AML, balanced chromosomal
      translocations, abnormalities of chromosome 11q23 (1%) and Tp53 mutations (<2%)
      were uncommon. Molecularly integrated CMML prognostic models were not effective
      in risk stratifying t-CMML patients and responses to hypomethylating agents were
      dismal with no complete responses. Median overall (OS) and leukemia free survival
      (LFS) was shorter for t-CMML in comparison to d-CMML (Median OS 10.9 vs 26 months
      and median LFS 50 vs 127 months) and t-CMML independently and adversely impacted
      OS (P = .0001 HR 2.1 95% CI 1.4-3.0). This prognostic impact was retained in the
      context of the Mayo Molecular Model (P = .001, HR 2.4, 95% CI 1.5-3.7) and the
      GFM prognostic model (P < .0001, HR 2.15, 95% CI 1.5-3.7). In summary, we
      highlight the unique genetics and independent prognostic impact of t-CMML,
      warranting its inclusion as a separate entity in the classification schema for
      both CMML and t-MN.

PMID- 29023993
TI  - Pediatric keloids: A 6-year retrospective review.
AB  - BACKGROUND/OBJECTIVES: Keloids are reportedly rare at the extremes of life. We
      sought to describe the epidemiology of pediatric keloids seen at the plastic
      surgery outpatient department of the University College Hospital, Ibadan.
      METHODS: We retrospectively reviewed all children younger than 19 years who
      presented with nonburn keloids between 2008 and 2014. Data were obtained on age;
      duration, size, and location of the keloid; family history; mode of treatment;
      and outcome. Outcome variables were recurrence and wound complications. Data were
      analyzed using the Pearson chi-square test for discreet variables and the
      independent-sample t test for continuous variables. P < .05 was taken as
      statistically significant. RESULTS: Within the review period, 304 patients
      presented with keloids, of whom 40 (13.1%) were younger than 19 years. There was
      a female preponderance (n = 23, 57.5%). The mean age at onset of the keloid was
      9.3 years (range 3 months-18 years). Thirty (75%) patients had keloids in the
      head and neck region. Keloids were sporadic in 31 (77.5%) patients. Nineteen
      (47.5%) patients had multimodal treatment for keloid. The recurrence rate was
      20%. Recurrence was significantly associated with the size of the lesion (P =
      .003). CONCLUSION: Keloids during childhood are not rare. More attention should
      be paid to the management of keloids in this age group.

PMID- 29023994
TI  - Biosensors: Classifications, medical applications, and future prospective.
AB  - Biosensors are devices that combine a biological material with a suitable
      platform for detection of pathogenic organisms, carcinogenic, mutagenic, and/or
      toxic chemicals or for reporting a biological effect. In recent years, an
      enormous number of different types of biosensors have been constructed and
      developed for several medical applications. The reason for that was primarily due
      to the numerous advantages and applications that can be offered by biosensors.
      This review article has been started with demonstrating the power of biosensor
      technologies versus analytical and conventional techniques. Subsequently, more
      emphasis has been added on the classification and the role of biosensors in
      several medical applications such as detection and monitoring of carcinogenic and
      mutagenic chemicals, reporting of endocrine disrupting compounds, and detection
      of pathogenic organisms. The most common reporter genes used in biosensors
      engineering and construction have also been summarized. Prospective strategies
      and recommendations for the future construction of biosensors have been
      highlighted.

PMID- 29023996
TI  - Effect of sex difference in clinical presentation (stable coronary artery disease
      vs unstable angina pectoris or non-ST-elevation myocardial infarction vs ST
      elevation myocardial infarction) on 2-year outcomes in patients undergoing
      percutaneous coronary intervention.
AB  - OBJECTIVE: To determine whether there is a difference in 2-year prognosis among
      patients across the spectrum of coronary artery disease undergoing percutaneous
      coronary intervention (PCI). METHODS: We analyzed all consecutive patients
      undergoing PCI at a single center from 1/1-12/31/2013. Clinical presentations
      were compared between sexes according to baseline clinical, angiographic, and
      procedural characteristics and 2-year (mean 730 +/- 30-day) outcomes. RESULTS: We
      grouped 10 724 consecutive patients based on sex and clinical presentation. Among
      patients with ST-elevation myocardial infarction (STEMI), rates of all-cause
      death (6.7% vs 1.4%) and cardiac death (3.8% vs 1.1%) were significantly higher
      in women than in men (P < 0.05), but these rates did not differ between men and
      women with stable coronary artery disease (SCAD) and non-ST-elevation acute
      coronary syndrome ((NSTE-ACS). Incidence of major bleeding was greater than in
      men only in those women presenting with ACS. After multivariable adjustment,
      female sex was not an independent predictor of outcomes in STEMI (hazard ratio
      [HR] for all-cause death: 1.33, 95% confidence interval [CI]:0.52-3.38; P = 0.55;
      HR for cardiac death: 0.69, 95%CI: 0.23-2.09, P = 0.51], but was still an
      independent predictor of bleeding in STEMI (HR: 3.53, 95%CI: 1.26-9.91, P =
      0.017). CONCLUSION: Among STEMI patients, women had worse 2-year mortality after
      PCI therapy, but female sex was not an independent predictor of mortality after
      adjustment for baseline characteristics. In STEMI patients, women were at higher
      bleeding risk than men after PCI, even after multivariable adjustment.

PMID- 29023997
TI  - Trans-acting oligodeoxythymidine phosphorothioate triester reagents for transient
      transfection optimized and facilitated by a high-throughput microbioreactor
      system.
AB  - A rapid and cost-effective transient transfection method for mammalian cells is
      essential for screening biopharmaceuticals in early stages of development. A
      library of 25 amphipathic trans-acting oligodeoxythymidine phosphorothioate
      triester (dTtaPS) transfection reagents, carrying positively charged and
      lipophilic groups, has been constructed for this purpose. High-throughput
      screening of the library, using an imaging cytometer and an automated
      microbioreactor system, has led to the identification of dTtaPS10+ as a potent
      transfection reagent. This reagent efficiently delivers a plasmid encoding
      enhanced green fluorescent protein in adherent HeLa cells while exhibiting low
      cytotoxicity. The microbioreactor system has been particularly useful for
      assessing the ability of dTtaPS10+ to deliver a plasmid encoding immunoglobulin
      IgG1 in a fed-batch serum-free suspension CHO cell culture; dTtaPS10+ -mediated
      transfection resulted in the production of IgG1 in yields comparable to or better
      than those obtained with commercial lipid-based transfection reagents under
      similar conditions. The ability of dTtaPS10+ to deliver plasmids is essentially
      unaffected by the presence of a silicone-based antifoaming reagent, which is
      commonly used in bioreactor cell cultures. The transfection efficiency of
      lyophilized dTtaPS10+ -plasmid complexes has been significantly restored upon
      aqueous reconstitution when compared to that achieved while using commercial
      transfection reagent complexes under similar conditions. The results of all
      experiments underscore the potential of dTtaPS10+ for transient transfection of
      plasmids into adherent cells and fed-batch serum-free suspension CHO cells and
      rapid screening of reagents in a microbioreactor system.

PMID- 29023998
TI  - Randomized controlled trial on the effectiveness of a multicomponent intervention
      on migraine: A study protocol.
AB  - AIM: To describe a randomized controlled trial protocol that evaluates the
      effectiveness of a multicomponent intervention in improving the outcomes (quality
      of life, disability, intensity, frequency and duration) of patients with
      migraine. BACKGROUND: Migraine affects various facets of Quality of Life and
      results in moderate to high levels of disability among migraineurs. Migraine pain
      can be intense and unremitting that can interfere with the daily routine and
      reduce the ability to think and function normally. Many people can lower their
      risk of a migraine by simply avoiding stress, getting enough sleep, eating
      regularly and by avoiding triggers. Hence, the present study aims at evaluating
      the effectiveness of a multicomponent intervention in managing migraine
      headaches. The multicomponent intervention includes behavioural lifestyle
      modification program and sessions of pranayama (a form of yogic breathing
      exercise). DESIGN: The study is a prospective, randomized, controlled, single
      blinded trial with parallel arms. METHODS: The study participants are randomized
      to intervention and control arms. The participants randomized to the intervention
      arm would receive the specific multicomponent intervention based on the protocol.
      The participants in the control arm would receive routine care. They are followed
      up for 24 weeks and the outcomes are assessed. DISCUSSION: Various studies report
      that non-pharmacological therapies and integrative therapies play a major role in
      the management of migraine headaches. The findings of the study are expected to
      open up new horizons in health care arena emphasizing the use of non
      pharmacological therapy for less focused areas of primary care health problems
      such as migraine. TRIAL REGISTRATION: The trial is registered with the Clinical
      Trials Registry India (CTRI). The CTRI India is one of the primary registries in
      the WHO registry network (Ctri.nic.in, ). CTRI reference ID: CTRI/2015/10/006282.

PMID- 29023999
TI  - Occupational exposure to diesel engine exhaust and serum cytokine levels.
AB  - The International Agency for Research on Cancer has classified diesel engine
      exhaust (DEE) as a human lung carcinogen. Given that inflammation is suspected to
      be an important underlying mechanism of lung carcinogenesis, we evaluated the
      relationship between DEE exposure and the inflammatory response using data from a
      cross-sectional molecular epidemiology study of 41 diesel engine testing workers
      and 46 unexposed controls. Repeated personal exposure measurements of PM2.5 and
      other DEE constituents were taken for the diesel engine testing workers before
      blood collection. Serum levels of six inflammatory biomarkers including
      interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, macrophage
      inflammatory protein (MIP)-1beta, and monocyte chemotactic protein (MCP)-1 were
      analyzed in all subjects. Compared to unexposed controls, concentrations of MIP
      1beta were significantly reduced by ~37% in DEE exposed workers (P < 0.001) and
      showed a strong decreasing trend with increasing PM2.5 concentrations in all
      subjects (Ptrend  < 0.001) as well as in exposed subjects only (Ptrend  = 0.001).
      Levels of IL-8 and MIP-1beta were significantly lower in workers in the highest
      exposure tertile of PM2.5 (>397 ug/m3 ) compared to unexposed controls. Further,
      significant inverse exposure-response relationships for IL-8 and MCP-1 were also
      found in relation to increasing PM2.5 levels among the DEE exposed workers. Given
      that IL-8, MIP-1beta, and MCP-1 are chemokines that play important roles in
      recruitment of immunocompetent cells for immune defense and tumor cell clearance,
      the observed lower levels of these markers with increasing PM2.5 exposure may
      provide insight into the mechanism by which DEE promotes lung cancer. Environ.
      Mol. Mutagen. 59:144-150, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29024001
TI  - Dynamin-related protein 1-mediated mitochondrial fission contributes to post
      traumatic cardiac dysfunction in rats and the protective effect of melatonin.
AB  - Mechanical trauma (MT) causes myocardial injury and cardiac dysfunction. However,
      the underlying mechanism remains largely unclear. This study investigated the
      role of mitochondrial dynamics in post-traumatic cardiac dysfunction and the
      protective effects of melatonin. Adult male Sprague Dawley rats were subjected to
      5-minute rotations (200 revolutions at a rate of 40 rpm) to induce MT model.
      Melatonin was administrated intraperitoneally 5 minute after MT. Mitochondrial
      morphology, myocardial injury, and cardiac function were determined in vivo.
      There was smaller size of mitochondria and increased number of mitochondria per
      MUm2 in the hearts after MT when the secondary myocardial injury was induced.
      Melatonin treatment at the dose of 30 mg/kg reduced serine 616 phosphorylation of
      Drp1 and inhibited mitochondrial Drp1 translocation and mitochondrial fission in
      the hearts of rats subjected to MT, which contributed to the reduction of
      myocardial injury and the improvement of cardiac function. In vitro, H9c2 cells
      cultured in 20% traumatic plasma (TP) for 12 hour showed enhanced mitochondrial
      fission, mitochondrial membrane potential (?Psim) loss, mitochondrial cytochrome
      c release, and decreased mitochondrial complex I-IV activities. Pretreatment with
      melatonin (100 MUmol/L) efficiently inhibited TP-induced mitochondrial fission,
      ?Psim loss, cytochrome c release, and improved mitochondrial function.
      Melatonin's protective effects were attributed to its role in suppressing plasma
      TNF-alpha overproduction, which was responsible for Drp1-mediated mitochondrial
      fission. Taken together, our results demonstrate for the first time that abnormal
      mitochondrial dynamics is involved in post-traumatic cardiac dysfunction.
      Melatonin has significant pharmacological potential in protecting against MT
      induced cardiac dysfunction by preventing excessive mitochondrial fission.

PMID- 29024000
TI  - Myeloid Notch1 deficiency activates the RhoA/ROCK pathway and aggravates
      hepatocellular damage in mouse ischemic livers.
AB  - : Notch signaling plays an emerging role in the regulation of immune cell
      development and function during inflammatory response. Activation of the ras
      homolog gene family member A/Rho-associated protein kinase (ROCK) pathway
      promotes leukocyte accumulation in tissue injury. However, it remains unknown
      whether Notch signaling regulates ras homolog gene family member A/ROCK-mediated
      immune responses in liver ischemia and reperfusion (IR) injury. This study
      investigated intracellular signaling pathways regulated by Notch receptors in the
      IR-stressed liver and in vitro. In a mouse model of IR-induced liver inflammatory
      injury, we found that mice with myeloid-specific Notch1 knockout showed
      aggravated hepatocellular damage, with increased serum alanine aminotransferase
      levels, hepatocellular apoptosis, macrophage/neutrophil trafficking, and
      proinflammatory mediators compared to Notch1-proficient controls. Unlike in the
      controls, myeloid Notch1 ablation diminished hairy and enhancer of split-1 (Hes1)
      and augmented c-Jun N-terminal kinase (JNK)/stress-activated protein kinase
      associated protein 1 (JSAP1), JNK, ROCK1, and phosphatase and tensin homolog
      (PTEN) activation in ischemic livers. Disruption of JSAP1 in myeloid-specific
      Notch1 knockout livers improved hepatocellular function and reduced JNK, ROCK1,
      PTEN, and toll-like receptor 4 activation. Moreover, ROCK1 knockdown inhibited
      PTEN and promoted Akt, leading to depressed toll-like receptor 4. In parallel in
      vitro studies, transfection of lentivirus-expressing Notch1 intracellular domain
      promoted Hes1 and inhibited JSAP1 in lipopolysaccharide-stimulated bone marrow
      derived macrophages. Hes1 deletion enhanced JSAP1/JNK activation, whereas
      clustered regularly interspaced short palindromic repeats/CRISPR-associated
      protein 9-mediated JSAP1 knockout diminished ROCK1/PTEN and toll-like receptor 4
      signaling. CONCLUSION: Myeloid Notch1 deficiency activates the ras homolog gene
      family member A/ROCK pathway and exacerbates hepatocellular injury by inhibiting
      transcriptional repressor Hes1 and inducing scaffold protein JSAP1 in IR
      triggered liver inflammation; our findings underscore the crucial role of the
      Notch-Hes1 axis as a novel regulator of innate immunity-mediated inflammation and
      imply the therapeutic potential for the management of organ IR injury in
      transplant recipients. (Hepatology 2018;67:1041-1055).

PMID- 29024002
TI  - Boundary-spanning actors in complex adaptive governance systems: The case of
      multisectoral nutrition.
AB  - A growing literature highlights complexity of policy implementation and
      governance in global health and argues that the processes and outcomes of
      policies could be improved by explicitly taking this complexity into account. Yet
      there is a paucity of studies exploring how this can be achieved in everyday
      practice. This study documents the strategies, tactics, and challenges of
      boundary-spanning actors working in 4 Sub-Saharan Africa countries who supported
      the implementation of multisectoral nutrition as part of the African Nutrition
      Security Partnership in Burkina Faso, Mali, Ethiopia, and Uganda. Three action
      researchers were posted to these countries during the final 2 years of the
      project to help the government and its partners implement multisectoral nutrition
      and document the lessons. Prospective data were collected through participant
      observation, end-line semistructured interviews, and document analysis. All 4
      countries made significant progress despite a wide range of challenges at the
      individual, organizational, and system levels. The boundary-spanning actors and
      their collaborators deployed a wide range of strategies but faced significant
      challenges in playing these unconventional roles. The study concludes that, under
      the right conditions, intentional boundary spanning can be a feasible and
      acceptable practice within a multisectoral, complex adaptive system in low- and
      middle-income countries.

PMID- 29024003
TI  - Molecular characterization of the llama FGF5 gene and identification of putative
      loss of function mutations.
AB  - Llama, the most numerous domestic camelid in Argentina, has good fiber-production
      ability. Although a few genes related to other productive traits have been
      characterized, the molecular genetic basis of fiber growth control in camelids is
      still poorly understood. Fibroblast growth factor 5 (FGF5) is a secreted
      signaling protein that controls hair growth in humans and other mammals.
      Mutations in the FGF5 gene have been associated with long-hair phenotypes in
      several species. Here, we sequenced the llama FGF5 gene, which consists of three
      exons encoding 813 bp. cDNA analysis from hair follicles revealed the expression
      of two FGF5 alternative spliced transcripts, in one of which exon 2 is absent.
      DNA variation analysis showed four polymorphisms in the coding region: a
      synonymous SNP (c.210A>G), a single base deletion (c.348delA), a 12-bp insertion
      (c.351_352insCATATAACATAG) and a non-sense mutation (c.499C>T). The deletion was
      always found together with the insertion forming a haplotype and producing a
      putative truncated protein of 123 amino acids. The c.499C>T mutation also leads
      to a premature stop codon at position 168. In both cases, critical functional
      domains of FGF5, including one heparin binding site, are lost. All animals
      analyzed were homozygous for one of the deleterious mutations or compound
      heterozygous for both (i.e. c.348delA, c.351_352insCATATAACATAG/c.499T).
      Sequencing of guanaco samples showed that the FGF5 gene encodes a full-length 270
      amino acid protein. These results suggest that FGF5 is likely functional in short
      haired wild species and non-functional in the domestic fiber-producing species,
      the llama.

PMID- 29024004
TI  - Shortening gestational age at term and organisation of birth care in the Czech
      Republic.
AB  - A trend of the shortening duration of pregnancies carried to term has been
      observed in several countries and represents a growing public health concern.
      This paper describes the trend in the Czech Republic and shows its relation to
      the changing demographic structure of mothers and the organisation of maternity
      care. Data from the birth register are used and supplemented with information
      about the capacity of maternity care (number of beds at maternity clinics, number
      of obstetricians and midwives). Logistic regression is used to estimate the odds
      of 37 to 39 vs 40+ completed weeks of gestation. The results show that the
      average gestational age at term decreased by 2.1 days between 2000 and 2013. The
      odds of 37 to 39 weeks of gestational duration increased, mainly due to the
      reduction in the number of beds at maternity clinics (adjusted odds ratio of
      1.51). The effects of the number of health care staff members were weaker. The
      number of midwives positively influenced gestational duration, while the number
      of obstetricians had a negative effect. Maternal demographic structure cannot
      explain the trend. A likely explanation is the increased use of planned early
      term caesarean sections.

PMID- 29024006
TI  - Ciliary body melanoma manifesting as unilateral ocular hypertension and early
      cataract.

PMID- 29024005
TI  - Functional Limitations Among Responders to the World Trade Center Attacks 14
      Years After the Disaster: Implications of Chronic Posttraumatic Stress Disorder.
AB  - Posttraumatic stress disorder (PTSD) is associated with self-reported
      difficulties navigating the social and physical world and may also be associated
      with risk of functional limitations. The Short Physical Performance Battery
      (SPPB), an objective functional assessment, was administered during monitoring
      exams between January and December 2015 to a consecutive sample of 1,268 rescue
      workers, volunteers, and other responders who had aided in response, recovery,
      and cleanup efforts at the World Trade Center (WTC) in New York after the
      September 11, 2011 attacks. Data were linked with diagnostic and longitudinal
      data from the WTC monitoring study. Multivariable analyses were used to examine
      predictors of functional limitations. Prevalence estimates weighted to the
      general responder population revealed a relatively high prevalence of functional
      limitations, SPPB <= 9; 16.0%, 95% CI [13.7, 18.4]. Current PTSD was associated
      with a twofold increased risk of functional limitations after controlling for
      predisposing factors, trauma severity, behavioral factors, and WTC-related
      medical conditions, adjusted risk ratio (aRR) = 2.11, 95% CI [1.48, 3.01].
      Exposure to ergonomic risk factors at the WTC also increased the risk of
      functional impairments, aRR = 1.34 95% CI [1.05, 1.70]. Longitudinal results
      suggest that individuals with current functional limitations experienced high
      baseline PTSD severity, B = 2.94, SE = 1.33, and increasing PTSD symptom
      severity, B = 0.29, SE = 0.10, since September 11, 2001. This study identified a
      cross-sectional relationship between functional limitations and PTSD and a
      worsening of PTSD symptoms in persons who eventually demonstrated functional
      limitations. Results highlight the potential role of chronic PTSD in functional
      limitations.

PMID- 29024007
TI  - SNP mutations occurring in thyroid hormone receptor influenced individual
      susceptibility to triiodothyronine: Molecular dynamics and site-directed
      mutagenesis approaches.
AB  - The increasing evidences have suggested that expression of single nucleotide
      polymorphisms (SNP) coded thyroid hormone receptors (THR) generally are
      associated with individual susceptibility to chemicals. In the present research,
      multiple molecular dynamics simulations on four SNP mutants (G332R, T337Delta,
      G345R, and G347E) were performed to investigate the structural and dynamical
      altering, which could lead to a binding capability variation to triiodothyronine
      (T3). It proved the structures of two SNP mutants (G345R and T337Delta) occurring
      in the THR proteins had experienced conformational change to a great extend,
      which also led to a significant decreasing in binding ability with T3. In
      addition, two mutates (G345R and G347E) and wild type THR proteins were expressed
      and purified based on site-directed mutagenesis technology to test their binding
      abilities with T3 by fluorescence experiments. The fluorescence quenching
      efficiencies of two mutates displayed that the conjugation with T3 decreased with
      a significant rate in G345R system and a little rate in G347E system compared
      with its wild type. It was consistent with the molecular dynamic research that
      the SNP mutations did change structures of THR protein, and thereby decreased the
      binding behavior of T3 at different extent. The overall molecular-level look at
      the protein structure may provide the structural basis to explain how one amino
      acid change can create a ripple effect on the protein structures and eventually
      affect the binding affinity of the ligands, which maybe the first stage to
      understand how SNP mutation results in individual difference in susceptibility to
      variant chemicals.

PMID- 29024008
TI  - Immunization with alpha-synuclein/Grp94 reshapes peripheral immunity and
      suppresses microgliosis in a chronic Parkinsonism model.
AB  - Neuroinflammation mediated by chronically activated microglia, largely caused by
      abnormal accumulation of misfolded alpha-synuclein (alphaSyn) protein, is known
      to contribute to the pathophysiology of Parkinson's disease (PD). In this work,
      based on the immunomodulatory activities displayed by particular heat-shock
      proteins (HSPs), we tested a novel vaccination strategy that used a combination
      of alphaSyn and Grp94 (HSPC4 or Gp96) chaperone and a murine PD model. We used
      two different procedures, first, the adoptive transfer of splenocytes from
      alphaSyn/Grp94-immunized mice to recipient animals, and second, direct
      immunization with alphaSyn/Grp94, to study the effects in a chronic mouse MPTP
      model of parkinsonism. We found that both approaches promoted a distinct profile
      in the peripheral system-supported by humoral and cellular immunity-consisting of
      a Th1-shifted alphaSyn-specific response accompanied by an immune-regulatory/Th2
      skewed general phenotype. Remarkably, this mixed profile sustained by
      alphaSyn/Grp94 immunization led to strong suppression of microglial activation in
      the substantia nigra and striatum, pointing to a newly described positive effect
      of anti-alphaSyn Th1-responses in the context of PD. This strategy is the first
      to target alphaSyn and report the suppression of PD-associated microgliosis.
      Overall, we show that the alphaSyn/Grp94 combination supports a distinct and long
      lasting immune profile in the peripheral system, which has an impact at the CNS
      level by suppressing chronic microglial activation in an MPTP model of PD.
      Furthermore, our study demonstrates that reshaping peripheral immunity by
      vaccination with appropriate misfolding protein/HSP combinations could be highly
      beneficial as a treatment for neurodegenerative misfolding diseases.

PMID- 29024009
TI  - Is kidney transplantation safe after careful selection of the recipients with a
      history of psychotic disorder?

PMID- 29024011
TI  - Gastrointestinal: Phlebosclerotic colitis: A rare but increasingly recognized
      cause of ischemic colitis with telltale imaging features.

PMID- 29024010
TI  - Imaging behind occluded areas with an iatrogenic perforated balloon: A safe,
      practical, and simple new method of visualizing the distal lumen in total
      occlusion.
AB  - OBJECTIVE: In the present study, we investigated the effectiveness and
      reliability of a new method that reveals whether guidewire advanced distal to the
      lesion is in the lumen in patients with acute (ATO) or chronic coronary total
      occlusion (CTO). METHODS: Forty-one patients with symptomatic ATO and 22 patients
      with CTO who were admitted into our catheterization laboratory between January
      2016 and March 2017 were included. In patients in whom antegrade filling could
      not be demonstrated after passing 0.014" guidewire beyond the total lesion, a
      1.25 * 15 mm balloon was punctured with a needle outside the operative field to
      visualize the total lesion. This perforated balloon was then used to deliver an
      opaque substance through this hole to visualize the distal part. RESULTS: The
      mean age of our 63 patients was 66 +/- 12 years. They had diabetes (57%),
      hypertension (100%), and a history of PCI (85%). The mean procedural time was 27
      +/- 6.8 min, and the mean volume of contrast material used was 93.9 +/- 24 mL.
      This technique was 100% successful in accurately demonstrating the distal lumen
      and preventing complications. CONCLUSION: This new method we developed is much
      simpler and more useful than other methods for visualization of the true lumen
      because we can re-orient the balloon at the time of opaque injection and use 190
      cm guidewire without additional costs. Additionally, one balloon is sufficient
      for the operation.

PMID- 29024013
TI  - Erratum.

PMID- 29024012
TI  - Gastrointestinal: Transurethral endoscopic retrograde pancreatography.

PMID- 29024014
TI  - Gastrointestinal: Cause or effect: A case of microcytic anemia.

PMID- 29024015
TI  - Hepatobiliary and Pancreatic: Fulminant liver failure from diffuse leukemoid
      hepatic infiltration of melanoma.

PMID- 29024017
TI  - Most common dermatology diagnoses to the emergency department in the paediatric
      population.

PMID- 29024016
TI  - Effects of fluoride on morphology, growth, development, and thyroid hormone of
      Chinese toad (Bufo gargarizans) embryos.
AB  - Excessive fluoride in natural water ecosystem has the potential to detrimentally
      affect amphibians, but little is known of such effects or underlying mechanisms
      in Bufo gargarizans embryos. In the present study, the effects of fluoride
      exposure on B. gargarizans embryos were investigated. First, fluoride teratogenic
      experiment showed that the 9 days EC50 of fluoride on B. gargarizans embryos was
      177.62 mg/L. Then, we studied the sublethal effects of fluoride on B. gargarizans
      embryos at control, 0.7, 4.1, 19.6, 41.9, and 62.7 mg/L fluoride concentration.
      Malformation, growth, and development of embryos were monitored, and type 2 and 3
      iodothyronine deiodinase (Dio2 and Dio3), thyroid hormone receptors (TRalpha and
      TRbeta) mRNA levels were measured. Our results showed the morphological
      malformations, such as tail curvature (lordosis), edema, cuticularized ciliated
      cells, and hyperplasia were occurred during fluoride exposure. Growth and
      development were all inhibited at 19.5, 41.9, and 62.7 mg/L fluoride-treated
      groups after 9 days' exposure. According to real-time PCR results, exposure to
      fluoride upregulated Dio3 and TRbeta mRNA expression and downregulated Dio2 and
      TRalpha mRNA level. All above indicated that excessive fluoride could induce
      morphology malformations, inhibit embryonic growth and development, and disrupt
      the normal function of maternal thyroid hormone in B. gargarizans embryos.
      Environ. Mol. Mutagen. 59:123-133, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29024019
TI  - Contributing to the growth of early career investigators.

PMID- 29024018
TI  - The Community Health Center Fund: What's At Risk?

PMID- 29024020
TI  - Hematological indices of injury to lightly oiled birds from the Deepwater Horizon
      oil spill.
AB  - Avian mortality events are common following large-scale oil spills. However, the
      sublethal effects of oil on birds exposed to light external oiling are not
      clearly understood. We found that American oystercatchers (area of potential
      impact n = 42, reference n = 21), black skimmers (area of potential impact n =
      121, reference n = 88), brown pelicans (area of potential impact n = 91,
      reference n = 48), and great egrets (area of potential impact n = 57, reference n
      = 47) captured between 20 June 2010 and 23 February 2011 following the Deepwater
      Horizon oil spill experienced oxidative injury to erythrocytes, had decreased
      volume of circulating erythrocytes, and showed evidence of a regenerative
      hematological response in the form of increased reticulocytes compared with
      reference populations. Erythrocytic inclusions consistent with Heinz bodies were
      present almost exclusively in birds from sites impacted with oil, a finding
      pathognomonic for oxidative injury to erythrocytes. Average packed cell volumes
      were 4 to 19% lower and average reticulocyte counts were 27 to 40% higher in
      birds with visible external oil than birds from reference sites. These findings
      provide evidence that small amounts of external oil exposure are associated with
      hemolytic anemia. Furthermore, we found that some birds captured from the area
      impacted by the spill but with no visible oiling also had erythrocytic inclusion
      bodies, increased reticulocytes, and reduced packed cell volumes when compared
      with birds from reference sites. Thus, birds suffered hematologic injury despite
      no visible oil at the time of capture. Together, these findings suggest that
      adverse effects of oil spills on birds may be more widespread than estimates
      based on avian mortality or severe visible oiling. Environ Toxicol Chem
      2018;37:451-461. (c) 2017 SETAC.

PMID- 29024021
TI  - Too many and too few: The paradoxical case of physicians in the Russian
      Federation.
AB  - There is a paradox characterising the Russian health workforce. By international
      standards, Russia has a very high number of physicians per capita but at the same
      time is confronted by chronic real shortages of qualified physicians. This paper
      explores the reasons for this paradox by examining the structural characteristics
      of health workforce development in the context of the Soviet legacy and the
      comparative performance of other European countries. The paper uses data on
      comparative health workforce dynamics to argue that Russia is a European laggard,
      before then evaluating recent and current policies within that context. The
      health workforce challenges facing all low- and middle-income countries are
      acute, and this paper confirms this IS the case for Russia-Europe's largest
      country. The paper argues that the physician shortage is driven by the model of
      health workforce development inherited from the Soviet period, with its emphasis
      on quantitative rather than structural indicators. We find that, in contrast to
      most European Union countries, Russia's stalled reform process leaves it facing a
      chronic shortage of appropriately trained physicians. We document the costs of
      failed and slow reforms during the last 2 decades, while cautiously welcoming
      some recent policy initiatives.

PMID- 29024022
TI  - Novel beta-catenin/farnesoid X receptor interaction regulates hepatic bile acid
      metabolism during cholestasis.

PMID- 29024023
TI  - Chronic active Epstein-Barr virus infection with cutaneous lymphoproliferation:
      haemophagocytosis in the skin and haemophagocytic syndrome.

PMID- 29024025
TI  - An exploratory, prospective, open-label trial of ingenol mebutate gel 0.05% for
      the treatment of external anogenital warts.
AB  - BACKGROUND: Anogenital warts (AGW) can cause physical discomfort and decreased
      quality of life. Recent case reports suggest that ingenol mebutate gel might be
      an effective treatment of AGW. OBJECTIVE: To explore primarily the safety, and
      secondarily the efficacy of ingenol mebutate gel 0.05% in patients with AGW.
      METHODS: This was an exploratory, open-label, 1-arm trial of ingenol mebutate gel
      0.05% administered up to three times to patients with AGW. Safety was assessed by
      occurrence and severity of local skin reactions (LSRs) and treatment-related
      adverse events (AEs). Efficacy was assessed by complete clearance and reduction
      in AGW count 14 days after last treatment, and recurrence 12 weeks after
      clearance. RESULTS: Of 41 patients enrolled, 40 received treatment and 26
      completed the trial. Patients had a median AGW count of 11.0 and AGW duration of
      3.0 years at baseline. All patients experienced transient LSRs following
      treatment with a maximum composite LSR score of 7.5 (on a scale from 0 to 18). A
      total of 93% of patients reported treatment-related AEs, most frequently pain
      (85%) and procedural complications (35%) due to smearing of the gel. 78% of
      patients took mild analgesics for the pain, typically for 1-2 days following
      treatment. The majority of AEs were of moderate-to-severe intensity. Seventeen of
      39 patients (43.6%) had complete clearance 14 days after last treatment, and AGW
      count was reduced by 90.9%. There was a tendency towards lower clearance rate in
      patients with longer duration of AGW. Eight of 14 patients (57.1%) had AGW
      recurrence 12 weeks after clearance. CONCLUSION: Ingenol mebutate gel was
      associated with a high number of AEs and withdrawals due to painful local and
      adjacent skin reactions. Furthermore, it showed promising efficacy in reducing
      AGW despite a difficult-to-treat population. Optimization of the formulation is
      warranted to improve the safety profile of the treatment.

PMID- 29024024
TI  - Altered Serum Thyrotropin Concentrations in Dogs with Primary Hypoadrenocorticism
      before and during Treatment.
AB  - BACKGROUND: Thyrotropin (TSH) can be increased in humans with primary
      hypoadrenocorticism (HA) before glucocorticoid treatment. Increase in TSH is a
      typical finding of primary hypothyroidism and both diseases can occur
      concurrently (Schmidt's syndrome); therefore, care must be taken in assessing
      thyroid function in untreated human patients with HA. OBJECTIVE: Evaluate whether
      alterations in cTSH can be observed in dogs with HA in absence of primary
      hypothyroidism. ANIMALS: Thirty dogs with newly diagnosed HA, and 30 dogs in
      which HA was suspected but excluded based on a normal ACTH stimulation test
      (controls) were prospectively enrolled. METHODS: cTSH and T4 concentrations were
      determined in all dogs and at selected time points during treatment
      (prednisolone, fludrocortisone, or DOCP) in dogs with HA. RESULTS: cTSH
      concentrations ranged from 0.01 to 2.6 ng/mL (median 0.29) and were increased in
      11/30 dogs with HA; values in controls were all within the reference interval
      (range: 0.01-0.2 ng/dL; median 0.06). There was no difference in T4 between dogs
      with increased cTSH (T4 range 1.0-2.1; median 1.3 MUg/dL) compared to those with
      normal cTSH (T4 range 0.5-3.4, median 1.4 MUg/dL; P=0.69) and controls (T4 range
      0.3-3.8, median 1.8 MUg/dL; P=0.35). After starting treatment, cTSH normalized
      after 2-4 weeks in 9 dogs and after 3 and 4 months in 2 without thyroxine
      supplementation. CONCLUSIONS AND CLINICAL RELEVANCE: Evaluation of thyroid
      function in untreated dogs with HA can lead to misdiagnosis of hypothyroidism;
      treatment with glucocorticoids for up to 4 months can be necessary to normalize
      cTSH.

PMID- 29024027
TI  - Rural Disparities in Alzheimer's Disease-Related Community Pharmacy Care in the
      United States.
AB  - PURPOSE: To examine the relationship between area population density and
      community pharmacy-based Alzheimer's Disease (AD)-related services: pharmacists'
      medication knowledge and counseling, immunizations, and in-stock cognitive
      enhancers in 3 predominantly rural regions of the United States. METHODS: A
      standardized interview was administered by telephone to a 100% sample of
      community pharmacies in 3 areas: Northern California/Southern Oregon (n = 206),
      North and South Dakota (n = 278), and West Virginia (n = 420). Key study outcomes
      included: pharmacists' medication knowledge, availability of immunization
      services, and cognitive enhancers in stock. Respondents were classified by
      population density (persons/mi2 ) by pharmacy location to evaluate the
      relationship between rurality and AD-related pharmacy services. Chi-squared and
      logistic regression analyses were performed using Stata 10.1. FINDINGS:
      Pharmacies in more rural areas (50.1-100.0, 25.1-50.0, and <=25.0 persons/mi2 )
      were about 50% less likely to offer immunizations (95% CI: 0.32-0.91; 0.32-0.76;
      0.28-0.80, respectively) compared to the least rural areas (>100.0 persons/mi2 ).
      Compared to the least rural areas, pharmacists in the most rural areas (<=25.0
      persons/mi2 ) were less likely to name >=2 gastrointestinal adverse effects of
      donepezil (OR = 0.50, 95% CI: 0.31-0.82) or have memantine XR 28 mg (OR = 0.61,
      95% CI: 0.41-0.89) and other surveyed medications (OR = 0.57, 95% CI: 0.39-0.82)
      in stock. CONCLUSIONS: We found disparities in AD-related services in community
      pharmacies located in more rural counties, wherein individuals with AD and their
      caregivers may face barriers to obtaining quality pharmaceutical care. There is a
      need to strengthen pharmacists' knowledge and improve pharmacy services to reduce
      disparities.

PMID- 29024026
TI  - Computational characterization of substrate and product specificities, and
      functionality of S-adenosylmethionine binding pocket in histone lysine
      methyltransferases from Arabidopsis, rice and maize.
AB  - Histone lysine methylation by histone lysine methyltransferases (HKMTs) has been
      implicated in regulation of gene expression. While significant progress has been
      made to understand the roles and mechanisms of animal HKMT functions, only a few
      plant HKMTs are functionally characterized. To unravel histone substrate
      specificity, degree of methylation and catalytic activity, we analyzed
      Arabidopsis Trithorax-like protein (ATX), Su(var)3-9 homologs protein (SUVH),
      Su(var)3-9 related protein (SUVR), ATXR5, ATXR6, and E(Z) HKMTs of Arabidopsis,
      maize and rice through sequence and structure comparison. We show that ATXs may
      exhibit methyltransferase specificity toward histone 3 lysine 4 (H3K4) and might
      catalyse the trimethylation. Our analyses also indicate that most SUVH proteins
      of Arabidopsis may bind histone H3 lysine 9 (H3K9). We also predict that SUVH7,
      SUVH8, SUVR1, SUVR3, ZmSET20 and ZmSET22 catalyse monomethylation or
      dimethylation of H3K9. Except for SDG728, which may trimethylate H3K9, all SUVH
      paralogs in rice may catalyse monomethylation or dimethylation. ZmSET11, ZmSET31,
      SDG713, SDG715, and SDG726 proteins are predicted to be catalytically inactive
      because of an incomplete S-adenosylmethionine (SAM) binding pocket and a post-SET
      domain. E(Z) homologs can trimethylate H3K27 substrate, which is similar to the
      Enhancer of Zeste homolog 2 of humans. Our comparative sequence analyses reveal
      that ATXR5 and ATXR6 lack motifs/domains required for protein-protein interaction
      and polycomb repressive complex 2 complex formation. We propose that subtle
      variations of key residues at substrate or SAM binding pocket, around the
      catalytic pocket, or presence of pre-SET and post-SET domains in HKMTs of the
      aforementioned plant species lead to variations in class-specific HKMT functions
      and further determine their substrate specificity, the degree of methylation and
      catalytic activity.

PMID- 29024029
TI  - Rosacea and subsequent diagnosis for Parkinson's disease: a large, urban, single
      center, US patient population retrospective study.

PMID- 29024028
TI  - Emotion Dysregulation and Social Support in PTSD and Depression: A Study of
      Trauma-Exposed Veterans.
AB  - Emotion dysregulation has been associated with impaired interpersonal functioning
      and increased risk of posttraumatic psychopathology. Given that social support is
      a robust predictor of psychiatric morbidity following trauma exposure, we
      examined whether emotion dysregulation was associated with posttraumatic
      psychopathology through its negative effect on social support. Using self-report
      data from 90 military veterans (89.9% men) enrolled in an outpatient
      psychotherapy program for posttraumatic stress disorder (PTSD), we found that
      social support partially mediated the effect of emotion dysregulation on PTSD (PM
      = .10) and depression symptoms (PM = .14). When source of support was considered,
      friend (PM = .08) and significant other support (PM = .06) were greater mediators
      of the effect of emotion dysregulation on depression symptoms than family support
      (PM = .01). There were no differential mediating effects for support providers on
      PTSD symptoms. Our findings indicate that social support is a statistically
      significant yet clinically limited mechanism through which emotion dysregulation
      is linked with psychiatric symptoms. Implications for these limitations and
      alternative potentially relevant interpersonal mechanisms are discussed.

PMID- 29024031
TI  - First-genetic analysis of atypical phenotype of pseudoxanthoma elasticum with
      ocular manifestations in the absence of characteristic skin lesions.

PMID- 29024030
TI  - Melatonin prevents endothelial cell pyroptosis via regulation of long noncoding
      RNA MEG3/miR-223/NLRP3 axis.
AB  - Atherosclerosis (AS) is an inflammatory disease linked to endothelial
      dysfunction. Melatonin is reported to possess substantial anti-inflammatory
      properties, which has proven to be effective in AS. Emerging literature suggests
      that pyroptosis plays a critical role during AS progression. However, whether
      pyroptosis contributes to endothelial dysfunction and the underlying molecular
      mechanisms remained unexploited. This study was designed to investigate the
      antipyroptotic effects of melatonin in atherosclerotic endothelium and to
      elucidate the potential mechanisms. In this study, high-fat diet (HFD)-treated
      ApoE-/- mice were used as an atherosclerotic animal model. We found intragastric
      administration of melatonin for 12 weeks markedly reduced the atherosclerotic
      plaque in aorta. Meanwhile, melatonin also attenuated the expression of
      pyroptosis-related genes, including NLRP3, ASC, cleaved caspase1, NF
      kappaB/GSDMD, GSDMD N-termini, IL-1beta, and IL-18 in aortic endothelium of
      melatonin-treated animals. Consistent antipyroptotic effects were also observed
      in ox-LDL-treated human aortic endothelial cells (HAECs). We found that lncRNA
      MEG3 enhanced pyroptosis in HAECs. Moreover, MEG3 acted as an endogenous sponge
      by sequence complementarity to suppress the function of miR-223 and to increase
      NLRP3 expression and enhance endothelial cell pyroptosis. Furthermore, knockdown
      of miR-223 blocked the antipyroptotic actions of melatonin in ox-LDL-treated
      HAECs. Together, our results suggest that melatonin prevents endothelial cell
      pyroptosis via MEG3/miR-223/NLRP3 axis in atherosclerosis, and therefore,
      melatonin replacement might be considered a new strategy for protecting
      endothelium against pyroptosis, thereby for the treatment of atherosclerosis
      associated with pyroptosis.

PMID- 29024032
TI  - Que faire? A Bioeconomy and Solar Energy Institute at Italy's Research Council in
      the Context of the Global Transition to the Solar Economy.
AB  - Driven by insight for which new research and education requires new institutional
      organisation, and drawing on two decades of research and educational efforts, we
      devise the profile and activities of a new bioeconomy and solar energy institute
      at Italy's Research Council. We further articulate the institute's activities
      suggesting avenues on how to deploy sound and giving more useful research,
      education and policy advice in these crucial fields for making tomorrow's common
      development sustainable. The outcomes of the study are of general interest,
      because the transition to a solar economy is of intrinsic global nature and the
      challenges involved are similar in many countries.

PMID- 29024034
TI  - Maternal control of embryogenesis by MPK6 and its upstream MKK4/MKK5 in
      Arabidopsis.
AB  - In flowering plants, developing embryos reside in maternal sporophytes. It is
      known that maternal generation influences the development of next-generation
      embryos; however, little is known about the signaling components in the process.
      Previously, we demonstrated that Arabidopsis mitogen-activated protein kinase 6
      (MPK6) and MPK3 play critical roles in plant reproduction. In addition, we
      noticed that a large fraction of seeds from mpk6 single-mutant plants showed a
      wrinkled seed coat or a burst-out embryo phenotype. Here, we report that these
      seed phenotypes can be traced back to defective embryogenesis. The defective
      embryos have shorter suspensors and reduced growth along the longitudinal axis.
      Furthermore, the cotyledons fail to bend over to progress to the bent-cotyledon
      stage. As a result of the uneven circumference along the axis, the seed coat
      wrinkles to develop raisin-like morphology after dehydration. In more severe
      cases, the embryo can be pushed out from the micropylar end, resulting in the
      burst-out embryo seed phenotype. Genetic analyses demonstrated that the defective
      embryogenesis of the mpk6 mutant is a maternal effect. Heterozygous or homozygous
      mpk6 embryos have defects only in mpk6 homozygous maternal plants, but not in
      wild-type or heterozygous maternal plants. The loss of function of MKK4/MKK5 also
      results in the same phenotypes, suggesting that MKK4/MKK5 might act upstream of
      MPK6 in this pathway. The maternal-mediated embryo defects are associated with
      changes in auxin activity maxima and PIN localization. In summary, this research
      demonstrates that the Arabidopsis MKK4/MKK5-MPK6 cascade is an important player
      in the maternal control of embryogenesis.

PMID- 29024033
TI  - Impact of X-irradiation on microglia.
AB  - Irradiation is widely used to treat brain tumors, and also to create bone marrow
      (BM) chimeras. BM chimeras are widely used to dissect functions and origin of
      microglia and blood-derived mononuclear cells under homeostatic or pathological
      conditions. This is facilitated by the fact that microglia survive irradiation
      and are thus regarded radio-resistant. In this study, we tested whether microglia
      are indeed radio-resistant and looked for potential mechanisms that might explain
      this phenomenon. We analyzed the radio-resistance of microglia independently of
      their physiological brain environment compared to other mononuclear cells from
      spleen and brain after X-irradiation with 7 Gy or 30 Gy. Furthermore, we
      investigated long-term effects of X-irradiation on microglia using organotypic
      hippocampal slice cultures (OHSCs). We found a significant higher survival rate
      of isolated microglia 4 hr after X-irradiation with 30 Gy accompanied by a
      decreased proliferation rate. Investigations of apoptosis-related genes revealed
      no regulation of a specific antiapoptotic pathway but ataxia telangiectasia
      mutated (ATM), a DNA-repair-related gene, was significantly upregulated in
      isolated microglia 4 hr after 30 Gy. Irradiation of OHSCs with 7 and 30 Gy
      revealed a highly and significantly decreased cell number, morphological changes
      and an increase in migration velocity of microglia. Furthermore, cell loss,
      increased soma size and process length of microglia was also found in BM chimeras
      irradiated with 9.5 Gy 5 weeks after irradiation. Here, we present new evidence
      implying that microglia are not a homogeneous population of radio-resistant cells
      and report on long-term alterations of microglia that survived irradiation.

PMID- 29024036
TI  - How and why do countries differ in their governance and financing-related
      administrative expenditure in health care? An analysis of OECD countries by
      health care system typology.
AB  - INTRODUCTION: Administration is vital for health care. Its importance may
      increase as health care systems become more complex, but academic attention has
      remained minimal. We investigated trends in administrative expenditure across
      OECD countries, cross-country spending differences, spending differences between
      health care system typologies, and differences in the scale and scope of
      administrative functions across typologies. METHODS: We used OECD data, which
      include health system governance and financing-related administrative activities
      by regulators, governance bodies, and insurers (macrolevel), but exclude
      administrative expenditure by health care providers (mesolevel and microlevel).
      RESULTS: We find that governance and financing-related administrative spending at
      the macrolevel has remained stable over the last decade at slightly over 3% of
      total health spending. Cross-country differences range from 1.3% of health
      spending in Iceland to 8.3% in the United States. Voluntary private health
      insurance bears much higher administrative costs than compulsory schemes in all
      countries. Among compulsory schemes, multiple payers exhibit significantly higher
      administrative spending than single payers. Among single-payer schemes, those
      where entitlements are based on residency have significantly lower administrative
      spending than those with single social health insurance, albeit with a small
      difference. DISCUSSION: These differences can partially be explained because
      multi-payer and voluntary private health insurance schemes require additional
      administrative functions and enjoy less economies of scale. Studies in hospitals
      and primary care indicate similar differences in administrative costs across
      health system typologies at the mesolevel and microlevel of health care delivery,
      which warrants more research on total administrative costs at all the levels of
      health systems.

PMID- 29024035
TI  - The role of human papillomavirus in p16-positive oral cancers.
AB  - BACKGROUND: The aim of this study was to identify the presence and frequency of
      human papillomavirus (HPV) nucleic acid in p16-positive oral squamous cell
      carcinomas (OSCCs), to assess whether the virus was transcriptionally active and
      to assess the utility of p16 overexpression as a surrogate marker for HPV in
      OSCC. METHODS: Forty-six OSCC patients treated between 2007 and 2011 with
      available formalin-fixed paraffin-embedded (FFPE) specimens were included. Twenty
      three patients were positive for p16 by immunohistochemistry (IHC) and these were
      matched with 23 patients with p16-negative tumours. Laser capture microdissection
      of the FFPE OSCC tissues was undertaken to isolate invasive tumour tissue. DNA
      was extracted and tested for high-risk HPV types using a PCR-ELISA method based
      on the L1 SPF10 consensus primers, and a real-time PCR method targeting HPV-16
      and HPV-18 E6 region. Genotyping of HPV-positive cases was performed using a
      reverse line blot hybridization assay (Inno-LiPA). RNAScope(r) (a chromogenic RNA
      in situ hybridization assay) was utilized to detect E6/E7 mRNA of known high-risk
      HPV types for detection of transcriptionally active virus. RESULTS: HPV DNA was
      found in 3 OSCC cases, all of which were p16 IHC-positive. Two cases were
      genotyped as HPV-16 and one as HPV-33. Only one of the HPV-16 cases was confirmed
      to harbour transcriptionally active virus via HPV RNA ISH. CONCLUSION: We have
      shown that the presence of transcriptionally active HPV rarely occurs in OSCC and
      that p16 is not an appropriate surrogate marker for HPV in OSCC cases. We propose
      that non-viral mechanisms are responsible for the majority of IHC p16
      overexpression in OSCC.

PMID- 29024037
TI  - Reply.

PMID- 29024038
TI  - Baseline laboratory parameters predicting clinical outcome in melanoma patients
      treated with ipilimumab: a single-centre analysis.
AB  - BACKGROUND: Overall response rates (ORRs) for ipilimumab in advanced melanoma are
      only about 10%. Hence, it is important to explore biomarkers predicting
      ipilimumab responders. OBJECTIVE: We aimed to explore biomarkers to predict
      therapy outcome in melanoma patients who have undergone standard ipilimumab
      therapy in a real-world setting. METHODS: Databases of cutaneous melanoma
      patients (n = 52) who had received ipilimumab were reviewed and data collected on
      patient characteristics and diverse laboratory parameters. We performed
      univariate and multivariate statistics including logistic regression analysis and
      Cox proportional-hazards regression. RESULTS: Baseline leucocytes, lymphocytes,
      eosinophils, thrombocytes, neutrophil/lymphocyte ratio, thrombocytes/lymphocyte
      ratio, eosinophil/lymphocyte ratio and serum vitamin D levels were not
      significantly associated with ORR, progression-free survival (PFS) and melanoma
      specific survival (MSS). Multivariate analysis confirmed anti-PD-1 pretreatment
      as significant predictor for ORR following ipilimumab therapy. Low-LDH levels and
      more than two ipilimumab cycles turned out to be significant independent
      predictors for prolonged PFS. Low-S100B levels and anti-PD-1 treatment before or
      after ipilimumab were significant independent predictors for improved MSS. All
      aforementioned parameters and faecal calprotectin did not turn out to be
      predictors for ipilimumab-induced autoimmune-related adverse events and
      autoimmune colitis, respectively. CONCLUSIONS: Low serum LDH before ipilimumab
      treatment is an independent predictor for improved PFS. Furthermore, low serum
      S100B is an independent predictor for MSS. The number of ipilimumab cycles (>2)
      is significantly associated with prolonged PFS. Pretreatment calprotectin does
      not predict the occurrence of autoimmune colitis under ipilimumab therapy.

PMID- 29024039
TI  - The Electrical and Optical Properties of Organometal Halide Perovskites Relevant
      to Optoelectronic Performance.
AB  - Organometal halide perovskites are under intense study for use in
      optoelectronics. Methylammonium and formamidinium lead iodide show impressive
      performance as photovoltaic materials; a premise that has spurred investigations
      into light-emitting devices and photodetectors. Herein, the optical and
      electrical material properties of organometal halide perovskites are reviewed. An
      overview is given on how the material composition and morphology are tied to
      these properties, and how these properties ultimately affect device performance.
      Material attributes and techniques used to estimate them are analyzed for
      different perovskite materials, with a particular focus on the bandgap, mobility,
      diffusion length, carrier lifetime, and trap-state density.

PMID- 29024040
TI  - Metal-Halide Perovskite Transistors for Printed Electronics: Challenges and
      Opportunities.
AB  - Following the unprecedented rise in photovoltaic power conversion efficiencies
      during the past five years, metal-halide perovskites (MHPs) have emerged as a new
      and highly promising class of solar-energy materials. Their extraordinary
      electrical and optical properties combined with the abundance of the raw
      materials, the simplicity of synthetic routes, and processing versatility make
      MHPs ideal for cost-efficient, large-volume manufacturing of a plethora of
      optoelectronic devices that span far beyond photovoltaics. Herein looks beyond
      current applications in the field of energy, to the area of large-area
      electronics using MHPs as the semiconductor material. A comprehensive overview of
      the relevant fundamental material properties of MHPs, including crystal
      structure, electronic states, and charge transport, is provided first.
      Thereafter, recent demonstrations of MHP-based thin-film transistors and their
      application in logic circuits, as well as bi-functional devices such as light
      sensing and light-emitting transistors, are discussed. Finally, the challenges
      and opportunities in the area of MHPs-based electronics, with particular emphasis
      on manufacturing, stability, and health and environmental concerns, are
      highlighted.

PMID- 29024041
TI  - Strength training improves double-poling performance after prolonged submaximal
      exercise in cross-country skiers.
AB  - The purpose of this study was to investigate the effects of adding strength
      training with or without vibration to cross-country (XC) skiers' endurance
      training on double-poling (DP) performance, physiological, and kinematic
      adaptations. Twenty-one well-trained male XC-skiers combined endurance- and upper
      body strength training three times per week, either with (n = 11) or without (n =
      10) superimposed vibrations for 8 weeks, whereas eight skiers performed endurance
      training only (CON). Testing included 1RM in upper-body exercises, work economy,
      neural activation, oxygen saturation in muscle, and DP kinematics during a
      prolonged submaximal DP roller ski test which was directly followed by a time to
      exhaustion (TTE) test. TTE was also performed in rested state, and the difference
      between the two TTE tests (TTEdiff ) determined the ability to maintain DP
      performance after prolonged exercise. Vibration induced no additional effect on
      strength or endurance gains. Therefore, the two strength training groups were
      pooled (STR, n = 21). 1RM in STR increased more than in CON (P < .05), and there
      were no differences in changes between STR and CON in any measurements during
      prolonged submaximal DP. STR improved TTE following prolonged DP (20 +/- 16%, P <
      .001) and revealed a moderate effect size compared to CON (ES = 0.80; P = .07).
      Furthermore, STR improved TTEdiff more than CON (P = .049). In conclusion, STR
      superiorly improved 1RM strength, DP performance following prolonged submaximal
      DP and TTEdiff , indicating a specific effect of improved strength on the ability
      to maintain performance after long-lasting exercise.

PMID- 29024042
TI  - Pro-inflammatory M1 macrophage enhances metastatic potential of ovarian cancer
      cells through NF-kappaB activation.
AB  - Obesity is a serious health problem and critically related to poor prognosis in
      cancer, presumably through induction of chronic inflammation. The major culprit
      for cancer progression in obesity is presumed to be macrophages. Accumulation of
      macrophages in adipose tissue due to obesity induced chronic inflammation has
      been observed. However, obesity-induced macrophage accumulation related to
      ovarian cancer progression remains unclear. So, the role of macrophage in cancer
      progression is needed to be further defined for therapeutic intervention. Here we
      determined the effect of macrophage type 1 (M1 macrophage) on ovarian cancer
      cells in relation to the metastasis. Ovarian cancer cell lines (PA-1, SKOV3) and
      monocyte-derived macrophages were used in this study. Treatment with M1
      macrophage conditioned media on ovarian cancer cells increased the metastatic
      potential, such as migration and invasion capabilities. Interestingly, upon
      treatment with M1 macrophage conditioned media, nuclear translocation of NF
      kappaB, p60, and p50, from the cytosol was enhanced together with increased
      transcriptional activity of the NF-kappaB. Pre-treatment with TPCK (NF-kappaB
      inhibitor) and NF-kappaB siRNA on ovarian cancer cells suppressed M1 macrophage
      induced metastatic potential. Furthermore, Treatment of TNF-alpha on ovarian
      cancer cells showed NF-kappaB activation. Co-treatment with TNF-alpha inhibitor,
      etanercept, and M1 macrophage conditioned media on ovarian cancer cell lines
      reversed M1 macrophage conditioned media induced NF-kappaB activation. Taken
      together, TNF-alpha released from M1 macrophage increased metastatic potential in
      ovarian cancer cells through the activation of NF-kappaB signaling pathway. These
      results provide a new insight into the critical role of M1 macrophage in the
      tumor microenvironment in ovarian cancer.

PMID- 29024044
TI  - 4D Biofabrication Using Shape-Morphing Hydrogels.
AB  - Despite the tremendous potential of bioprinting techniques toward the fabrication
      of highly complex biological structures and the flourishing progress in 3D
      bioprinting, the most critical challenge of the current approaches is the
      printing of hollow tubular structures. In this work, an advanced 4D
      biofabrication approach, based on printing of shape-morphing biopolymer
      hydrogels, is developed for the fabrication of hollow self-folding tubes with
      unprecedented control over their diameters and architectures at high resolution.
      The versatility of the approach is demonstrated by employing two different
      biopolymers (alginate and hyaluronic acid) and mouse bone marrow stromal cells.
      Harnessing the printing and postprinting parameters allows attaining average
      internal tube diameters as low as 20 um, which is not yet achievable by other
      existing bioprinting/biofabrication approaches and is comparable to the diameters
      of the smallest blood vessels. The proposed 4D biofabrication process does not
      pose any negative effect on the viability of the printed cells, and the self
      folded hydrogel-based tubes support cell survival for at least 7 d without any
      decrease in cell viability. Consequently, the presented 4D biofabrication
      strategy allows the production of dynamically reconfigurable architectures with
      tunable functionality and responsiveness, governed by the selection of suitable
      materials and cells.

PMID- 29024043
TI  - Proteomic analysis of the venom of the predatory ant Pachycondyla striata
      (Hymenoptera: Formicidae).
AB  - The ants use their venom for predation, defense, and communication. The venom of
      these insects is rich in peptides and proteins, and compared with other animal
      venoms, ant venoms remain poorly explored. The objective of this study was to
      evaluate the protein content of the venom in the Ponerinae ant Pachycondyla
      striata. Venom samples were collected by manual gland reservoir dissection, and
      samples were submitted to two-dimensional gel electrophoresis and separation by
      ion-exchange and reverse-phase high-performance liquid chromatography followed by
      mass spectrometry using tanden matrix-assisted laser desorption/ionization with
      time-of-flight (MALDI-TOF/TOF) mass spectrometry and electrospray ionization
      quadrupole with time-of-flight (ESI-Q/TOF) mass spectrometry for obtaining amino
      acid sequence. Spectra obtained were searched against the NCBInr and SwissProt
      database. Additional analysis was performed using PEAKS Studio 7.0 (Sequencing de
      novo). The venom of P. striata has a complex mixture of proteins from which 43
      were identified. Within the identified proteins are classical venom proteins
      (phospholipase A, hyaluronidase, and aminopeptidase N), allergenic proteins
      (different venom allergens), and bioactive peptides (U10-ctenitoxin Pn1a). Venom
      allergens are among the most expressed proteins, suggesting that P. striata venom
      has high allergenic potential. This study discusses the possible functions of the
      proteins identified in the venom of P. striata.

PMID- 29024045
TI  - Association Between Dietary Fiber Intake and Bone Loss in the Framingham
      Offspring Study.
AB  - Dietary fiber may increase calcium absorption, but its role in bone
      mineralization is unclear. Furthermore, the health effect of dietary fiber may be
      different between sexes. We examined the association between dietary fiber (total
      fiber and fiber from cereal, fruits, vegetables, nuts, and legumes) and bone loss
      at the femoral neck, trochanter, and lumbar spine (L2 to L4 ) in older men and
      women. In the Framingham Offspring Study, at baseline (1996-2001), diet was
      assessed using the Willett food-frequency questionnaire, and bone mineral density
      (BMD) was measured using dual-energy X-ray absorptiometry. Follow-up BMD was
      measured in 2001-2005 and 2005-2008 among 792 men (mean age 58.1 years; BMI 28.6
      kg/m2 ) and 1065 women (mean age 57.3 years; BMI 27.2 kg/m2 ). We used sex
      specific generalized estimating equations in multivariable regressions to
      estimate the difference (beta) of annualized BMD change in percent (%DeltaBMD) at
      each skeletal site per 5 g/d increase in dietary fiber. We further estimated the
      adjusted mean for bone loss (annualized %DeltaBMD) among participants in each
      higher quartile (Q2, Q3, or Q4) compared with those in the lowest quartile (Q1)
      of fiber intake. Higher dietary total fiber (beta = 0.06, p = 0.003) and fruit
      fiber (beta = 0.10, p = 0.008) was protective against bone loss at the femoral
      neck in men but not in women. When examined in quartiles, men in Q2-Q4 of total
      fiber had significantly less bone loss at the femoral neck versus those in Q1
      (all p < 0.04). For women, we did not observe associations with hip bone loss,
      although fiber from vegetables appeared to be protective against spine bone loss
      in women but not men. There were no associations with cereal fiber or nut and
      legume fiber and bone loss in men or women. Our findings suggest that higher
      dietary fiber may modestly reduce bone loss in men at the hip. (c) 2017 American
      Society for Bone and Mineral Research.

PMID- 29024046
TI  - Traumatic brain injury in the prodromal period of Parkinson's disease: A large
      epidemiological study using medicare data.
AB  - OBJECTIVE: Studies suggest a greater risk of Parkinson's disease (PD) after
      traumatic brain injury (TBI), but it is possible that the risk of TBI is greater
      in the prodromal period of PD. We aimed to examine the time-to-TBI in PD patients
      in their prodromal period compared to population-based controls. METHODS: We
      identified 89,790 incident PD cases and 118,095 comparable controls aged > 65
      years in 2009 using Medicare claims data. Using data from the preceding 5 years,
      we compared time-to-TBI in PD patients in their prodromal period to controls. We
      estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for TBI in a Cox
      regression, while adjusting for age, sex, race/ethnicity, modified Charlson
      comorbidity index, smoking, and alcohol use. RESULTS: Risk of TBI was greater in
      PD patients in their prodromal period across all age and sex groups, with HRs
      consistently increasing with proximity to PD diagnosis. HRs ranged from 1.64 (95%
      CI, 1.52, 1.77) 5 years preceding diagnosis to 3.93 (95% CI, 3.74, 4.13) in the
      year before. The interaction between PD, TBI, and time was primarily observed for
      TBI attributed to falls. Motor dysfunction and cognitive impairment, suggested by
      corresponding International Classification of Diseases, Ninth Revision codes,
      partially mediated the PD-TBI association. INTERPRETATION: There is a strong
      association between PD and a recent TBI in the prodromal period of PD. This
      association strengthens as PD diagnosis approaches and may be a result of
      undetected nonmotor and motor symptoms, but confirmation will be required. Ann
      Neurol 2017;82:744-754.

PMID- 29024049
TI  - A cross-sectional study of the perceptions about triggering factors in acne
      patients.

PMID- 29024047
TI  - A Gallium Hydride as an Oxidizing Agent: Direct Synthesis of IrV Complexes via Ga
      H Bond Activation.
AB  - Reactions of the beta-diketiminate-stabilized gallium dihydride (Nacnac)Dipp GaH2
      with chelating IrI bis(phosphine) precursors under an H2 atmosphere are shown to
      provide a simple route to IrV complexes stabilized by strongly sigma-donating
      hydrides and the carbene-like (Nacnac)Dipp Ga donor. Characterization of these
      systems as seven-coordinate IrV tetrahydride species is supported by single
      crystal X-ray and neutron diffraction, and by T1 NMR measurements. By contrast
      related systems featuring more sterically demanding (non-chelating) ancillary
      ligands are better described in terms of a bis(hydride) dihydrogen [L3 Ir(H)2 (H2
      )]+ formulation and a formal IrIII oxidation state.

PMID- 29024048
TI  - The impact of adult-to-adult living donor liver transplantation on transplant
      center outcomes reporting.
AB  - BACKGROUND: The Scientific Registry of Transplant Recipients (SRTR) has released
      a 5-tier performance ranking system based upon results of deceased-donor and
      living-donor liver transplantation. MATERIALS AND METHODS: An analysis of Spring
      2017 SRTR Program Specific Reports for outcomes of adult living-donor and
      deceased-donor liver transplantation. RESULTS: Utilizing the current SRTR
      performance algorithm, living-donor liver transplant results may
      disproportionately affect transplant center performance ranking. CONCLUSION:
      Improvements in SRTR performance ranking including transparency in outcomes
      calculation, a calculating tool for transplant centers, and the potential
      reporting of living-donor outcomes as a separate report are necessary.

PMID- 29024050
TI  - Elastic Surface Model For Beta-Barrels: Geometric, Computational, And Statistical
      Analysis.
AB  - Over the past 2 decades, many different geometric models were created for beta
      barrels, including, but not limited to: cylinders, 1-sheeted hyperboloids,
      twisted hyperboloids, catenoids, and so forth. We are proponents of an elastic
      surface model for beta-barrels, which includes the minimal surface model as a
      particular case, but is a lot more comprehensive. Beta barrel models are obtained
      as numerical solutions of a boundary value problem, using the COMSOL Multiphysics
      Modeling Software. We have compared them against the best fitting statistical
      models, with positive results. The geometry of each individual beta barrel, as a
      rotational elastic surface, is determined by the ratio between the exterior
      diameter and the height. Through our COMSOL computational modeling, we created a
      rather large variety of generalized Willmore surfaces that may represent models
      for beta barrels. The catenoid is just a particular solution among all these
      shapes.

PMID- 29024051
TI  - Lifetime end-stage kidney disease risk estimation in living kidney donor
      candidates remains a challenge.

PMID- 29024052
TI  - Superlyophilic Interfaces and Their Applications.
AB  - Superlyophilic interfaces denote interfaces displaying strong affinity to diverse
      liquids, including superhydrophilic, superoleophilic, and superamphiphilic
      interfaces. When coming in contact with these interfaces, water or oil droplets
      tend to spread completely with contact angles close to 0 degrees , presenting
      versatile applications including self-cleaning, antifogging, controllable liquid
      transport, liquid separation, and so forth. Inspired by nature, scientists have
      developed various kinds of artificial superlyophilic (SLPL) interfaces in the
      past decades. In terms of dimensional characteristics, the artificial SLPL
      interfaces can be divided into four categories: i) 0D particles, whose
      dispersibility or catalytic performance can be notably enhanced by
      superlyophilicity; ii) 1D micro-/nanofibers or nanotubes/channels, which can
      efficiently transfer liquids with SLPL interfaces; iii) 2D flat SLPL interfaces,
      on which different functional molecules can be deposited uniformly, forming
      ultrathin and smooth films; and iv) 3D structures, which can be obtained by
      either constructing 0D, 1D, or 2D SLPL materials separately or directly
      fabricating random SLPL frameworks, and can always be used as functional coatings
      or bulk materials. Here, natural and artificial SLPL interfaces are briefly
      introduced, followed by a short discussion of the limit between lyophilicity and
      lyophobicity, and then a snapshot of methods to generate SLPL interfaces is
      given. Specific focus is placed on recent achievements of constructing SLPL
      interfaces from zero to three dimensions. Following that, broad applications of
      SLPL interfaces in commercial areas will be introduced. Finally, a short summary
      and outlook for future challenges in this field is presented.

PMID- 29024053
TI  - Direct effect of pholyphenol-rich plants, rooibos and ginkgo, on porcine ovarian
      cell functions.
AB  - The polyphenol-rich plants rooibos and ginkgo are widely used in folk medicine
      and in preparation of foods and drinks, but their effect on reproduction has not
      been properly studied yet. The aim of our in vitro experiments was to examine the
      possible direct effect of rooibos and ginkgo on the basic ovarian cell functions
      proliferation, apoptosis and release of hormones progesterone (P4) and leptin
      (L). Porcine ovarian granulosa cells were cultured in the presence of rooibos or
      ginkgo extract (0, 1, 10 and 100 MUg/ml of medium). The accumulation of markers
      of proliferation (PCNA and cyclin B1) and apoptosis (bax) and their mRNAs was
      analysed using immunocytochemistry and by reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR). Release of P4 and L was evaluated by
      radioimmunoassay. It was observed that rooibos or ginkgo addition was able to
      inhibit proliferation (down-regulates PCNA, cyclin B1 and their mRNAs), to
      promote apoptosis (accumulation of bax) and to suppress both L and P4 release by
      ovarian cells. These data suggest a direct inhibitory (anti-proliferative, pro
      apoptotic and hormone-suppressing) effect of polyphenol-containing plants rooibos
      and ginkgo on ovarian functions. The potential anti-reproductive effect of these
      medical plants is to be taken into account by their consumption.

PMID- 29024055
TI  - Metal-Ligand Multiple Bonding in Thorium Phosphorus and Thorium Arsenic
      Complexes.
AB  - The complexes (C5 Me5 )2 Th(EHTipp)2 , (E=P or As; Tipp=2,4,6
      triisopropylphenyl), provide a ligand framework that results in facile access to
      rare Th-E multiple bonds. The reaction of (C5 Me5 )2 Th(EHTipp)2 with KN(SiMe3 )2
      , proceeds cleanly to the desired bridging phosphinidiide or arsinidiide complex,
      [{(C5 Me5 )2 Th(MU2 -ETipp)(MU2 -EHTipp)}K]2 under ambient conditions. In the
      absence of a chelating agent, the potassium cation of one monomeric unit
      interacts with the aryl ring of a second monomer to form a bridged dimer. In the
      presence of 2,2,2-cryptand, the terminal phosphinidene complex, [(C5 Me5 )2
      Th=PTipp(PHTipp)][K(2,2,2-cryptand)] is isolated. Using X-ray crystallographic
      analysis, we have determined these complexes display the shortest Th-P and Th-As
      bond lengths reported.

PMID- 29024054
TI  - Multifunctional Nanohybrid Based on Porous Silicon Nanoparticles, Gold
      Nanoparticles, and Acetalated Dextran for Liver Regeneration and Acute Liver
      Failure Theranostics.
AB  - Herein, a novel nanohybrid based on porous silicon, gold nanoparticles (Au NPs),
      and acetalated dextran (DPSi/DAu@AcDEX) is reported to encapsulate and deliver
      one drug and increase the computer tomography (CT) signal for acute-liver-failure
      (ALF) theranostics. A microfluidic-assisted method is used to co-encapsulate
      different NPs in a single step. By alternating the surface properties of
      different NPs and by modulating the composition of the organic phase, both PSi
      and Au NPs are effectively encapsulated into the polymer matrix simultaneously,
      thus further achieving a multifunctional application. This system can be used to
      identify pathologically changes in the tissues and selectively deliver drugs to
      these sites. The loading of a therapeutic compound (XMU-MP-1) improves the drug
      solubility, precise, in situ drug delivery, and the drug-functioning time. In
      vivo results confirm a superior treatment effect and better compliance of this
      newly developed nanoformulation than free compound. This nanosystem plays a
      crucial role in targeting the lesion area, thus increasing the local drug
      concentration important for ALF reverse-effect. Moreover, the residence of Au NPs
      within the matrix further endows our system for CT-imaging. Altogether, these
      results support that this nanohybrid is a potential theranostic platform for ALF.

PMID- 29024056
TI  - Stereoselective Sulfinyl Aniline-Promoted Pd-Catalyzed C-H Arylation and
      Acetoxylation of Aliphatic Amides.
AB  - Stereoselective functionalization of aliphatic C-H bonds presents a great
      challenge. Following this target, we disclose herein an original strategy towards
      direct arylation of aliphatic chains at beta-methylene position based on a use of
      amide-sulfoxide bicoordinating directing group. Although moderate to high chiral
      induction (up to 9:1 d.r.) is achieved, diastereomerically pure compounds may be
      afforded by simple separation of diastereomeric products by silica gel
      chromatography. Accordingly, this reaction allows preparation of a large scope of
      high-value scaffolds in synthetically useful yields while recyclable character of
      our chiral auxiliary brings an additional benefit. A potential of this
      methodology to build up original molecules by sequential diarylation and
      expedient (two step) synthesis of a biologically active compound are further
      disclosed. Finally a first example of stereoselective direct acetoxylation of
      aliphatic chains is reported.

PMID- 29024058
TI  - Enantiopurity and absolute configuration determination of arene cis-dihydrodiol
      metabolites and derivatives using chiral boronic acids.
AB  - The relative merits of the methods employed to determine enantiomeric excess (ee)
      values and absolute configurations of chiral arene and alkene cis-1,2-diol
      metabolites, including boronate formation, using racemic or enantiopure (+) and (
      )-2-(1-methoxyethyl)phenylboronic acid (MEPBA), are discussed. Further
      applications of: 1) MEPBA derived boronates of chiral mono- and poly-cyclic arene
      cis-dihydrodiol, cyclohex-2-en-1-one cis-diol, heteroarene cis/trans-2,3-diol,
      and catechol metabolites in estimating their ee values, and 2) new chiral
      phenylboronic acids, 2-[1-methoxy-2,2-dimethylpropyl]phenyl boronic acid (MDPBA)
      and 2-[1-methoxy-1-phenylmethyl]phenyl boronic acid (MPPBA) and their advantages
      over MEPBA, as reagents for stereochemical analysis of arene and alkene cis-diol
      metabolites, are presented.

PMID- 29024057
TI  - Increasing candidaemia incidence from 2004 to 2015 with a shift in epidemiology
      in patients preexposed to antifungals.
AB  - Candidaemia is an important health problem in immunocompromised patients with an
      epidemiology varying with region, period and patient population involved. The
      occurrence of candidaemia and the associated species distribution over a 12-year
      period at a large tertiary care centre in Belgium were analysed. The trend in
      incidence in the intensive care units (ICUs) and non-ICUs was investigated as
      well as the influence of antifungal exposure on the species distribution. From
      2004 until 2015, 865 candidaemia episodes occurred in 826 patients at the
      University Hospitals Leuven. Candida albicans (59%) remained the most important
      cause of candidaemia, followed by C. glabrata (22.4%) and C. parapsilosis (8%).
      The mean incidence in the whole hospital was 1.48 per 10 000 patient days (PD).
      The incidence in ICUs increased reaching up to 10.7 per 10 000 PD whereas in the
      non-ICUs, the incidence decreased. Prior exposure to fluconazole and
      echinocandins was associated with candidaemia caused by less susceptible species.
      Candidaemia incidence increased in the whole hospital, driven by ICUs.
      Surveillance of candidaemia epidemiology on a local scale is of high value to
      guide empirical treatment strategies.

PMID- 29024059
TI  - Superaligned Carbon Nanotubes Guide Oriented Cell Growth and Promote
      Electrophysiological Homogeneity for Synthetic Cardiac Tissues.
AB  - Cardiac engineering of patches and tissues is a promising option to restore
      infarcted hearts, by seeding cardiac cells onto scaffolds and nurturing their
      growth in vitro. However, current patches fail to fully imitate the
      hierarchically aligned structure in the natural myocardium, the fast electrotonic
      propagation, and the subsequent synchronized contractions. Here, superaligned
      carbon-nanotube sheets (SA-CNTs) are explored to culture cardiomyocytes,
      mimicking the aligned structure and electrical-impulse transmission behavior of
      the natural myocardium. The SA-CNTs not only induce an elongated and aligned cell
      morphology of cultured cardiomyocytes, but also provide efficient extracellular
      signal-transmission pathways required for regular and synchronous cell
      contractions. Furthermore, the SA-CNTs can reduce the beat-to-beat and cell-to
      cell dispersion in repolarization of cultured cells, which is essential for a
      normal beating rhythm, and potentially reduce the occurrence of arrhythmias.
      Finally, SA-CNT-based flexible one-piece electrodes demonstrate a multipoint
      pacing function. These combined high properties make SA-CNTs promising in
      applications in cardiac resynchronization therapy in patients with heart failure
      and following myocardial infarctions.

PMID- 29024061
TI  - In vitro studies of the antimicrobial effect of non-thermal plasma-activated
      water as a novel mouthwash.
AB  - The aim of this study was to evaluate the antimicrobial effects of non-thermal
      plasma-activated water (PAW) as a novel mouthwash in vitro. Three representative
      oral pathogens - Streptococcus mutans, Actinomyces viscosus and Porphyromonas
      gingivalis - were treated with PAW. The inactivation effect was evaluated using
      the colony-forming unit (CFU) method, and the morphological and structural
      changes of a cell were observed by scanning electron microscopy and transmission
      electron microscopy (TEM). The physicochemical properties of PAW were analysed,
      and its influence on the leakage of intracellular proteins and DNA was evaluated.
      The results showed significant reduction of Streptococcus mutans within 60 s, of
      Actinomyces viscosus within 40 s, and of Porphyromonas gingivalis in less than 40
      s. Scanning electron microscopy and TEM images showed that the normal cell
      morphology changed by varying degrees after treatment with PAW. Intracellular
      proteins (280 nm) and DNA (260 nm) leaked from all three species of bacteria
      after treatment with PAW. Reactive oxygen species (ROS), especially atomic oxygen
      (O), hydroxyl radical (OH), and hydrogen peroxide (H2 O2 ), were generated and
      led to strong oxidative stress and cell damage. These results suggest that PAW
      has potential use as a novel antimicrobial mouthwash.

PMID- 29024062
TI  - Why run the risk? Motivation for offences by patients with substance use and
      antisocial personality disorders which they rated as most risky to their own well
      being.
AB  - BACKGROUND: Understanding motives for offending is important for the development
      and delivery of effective interventions. AIMS: To explore associations between
      variables with motivational implications and the offence committed in the past
      year rated by people with antisocial personality disorder and substance use
      disorder as putting them and their status at most risk. METHODS: Participants
      were 127 outpatients from a sample recruited for a pragmatic randomised
      controlled trial of an intervention for adults attending substance abuse
      treatment clinics in 13 municipalities in Denmark. Motives for offending were
      assessed on one occasion, using the Offending Motivation Questionnaire,
      aggression was assessed using the Buss-Perry Aggression Questionnaire and
      substance-related problems, including mental state difficulties, were assessed
      using the Substance Use Risk Profile. RESULTS: Attributing offending to
      provocation, excitement or financial gain differed substantially by type of
      offence, whereas attribution of offending to compliance did not. Personality
      scale scores were associated with attributing offences to provocation, excitement
      or compliance but not with financial gain. CONCLUSIONS: Motives for offending
      among substance users with antisocial personality disorder must be understood
      both in light of the type of offence and personality traits. Offending behaviour
      prevention strategies that draw on these distinctions, run in parallel to
      treatment for substance use, could improve reduction in recidivism. Copyright (c)
      2017 John Wiley & Sons, Ltd.

PMID- 29024060
TI  - Loss of Dnmt3b in Chondrocytes Leads to Delayed Endochondral Ossification and
      Fracture Repair.
AB  - Despite advanced understanding of signaling mediated by local and systemic
      factors, the role of epigenetic factors in the regulation of bone regeneration
      remains vague. The DNA methyltransferases (Dnmts) Dnmt3a and Dnmt3b have tissue
      specific expression patterns and create unique methylation signatures to regulate
      gene expression. Using a stabilized murine tibia fracture model we find that
      Dnmt3b is induced early in fracture healing, peaks at 10 days post fracture
      (dpf), and declines to nearly undetectable levels by 28 dpf. Dnmt3b expression
      was cell-specific and stage-specific. High levels were observed in chondrogenic
      lineage cells within the fracture callus. To determine the role of Dnmt3b in
      fracture healing, Agc1CreERT2 ;Dnmt3bf/f (Dnmt3bAgc1ER ) mice were generated to
      delete Dnmt3b in chondrogenic cells. Dnmt3bAgc1ER fracture displayed
      chondrogenesis and chondrocyte maturation defect, and a delay in the later events
      of angiogenesis, ossification, and bone remodeling. Biomechanical studies
      demonstrated markedly reduced strength in Dnmt3bAgc1ER fractures and confirmed
      the delay in repair. The angiogenic response was reduced in both vessel number
      and volume at 10 and 14 dpf in Dnmt3bAgc1ER mice. Immunohistochemistry showed
      decreased CD31 expression, consistent with the reduced angiogenesis. Finally, in
      vitro angiogenesis assays with human umbilical vein endothelial cells (HUVECs)
      revealed that loss of Dnmt3b in chondrocytes significantly reduced tube formation
      and endothelial migration. To identify specific angiogenic factors involved in
      the decreased callus vascularization, a protein array was performed using
      conditioned media isolated from control and Dnmt3b loss-of-function chondrocytes.
      Several angiogenic factors, including CXCL12 and osteopontin (OPN) were reduced
      in chondrocytes following loss of Dnmt3b. DNA methylation analysis further
      identified hypomethylation in Cxcl12 promoter region. Importantly, the defects in
      tube formation and cell migration could be rescued by administration of CXCL12
      and/or OPN. Altogether, our findings establish that Dnmt3b positively regulates
      chondrocyte maturation process, and its genetic ablation leads to delayed
      angiogenesis and fracture repair. (c) 2017 American Society for Bone and Mineral
      Research.

PMID- 29024063
TI  - Influence of ration composition on nutritive and digestive variables in captive
      giraffes (Giraffa camelopardalis) indicating the appropriateness of feeding
      practice.
AB  - The nutrition of captive giraffe (Giraffa camelopardalis), a browsing ruminant,
      is challenging because browse availability is limited in zoos and rations need to
      be composed of compensatory feeds. In this study, ration composition for giraffes
      in 12 German zoos was documented and linked to animal variables that indicate
      suitability of nutrition. Rations differed in proportion of ration items and
      chemical composition resulting in various grades of accordance with feeding
      recommendations. An estimated daily metabolisable energy (ME) intake (MEI; mean
      +/- SD) of 0.61 MJ ME/kg0.75 body weight (BW; +/-0.1) was sufficient to cover
      estimated energy requirements. Daily dry matter (DM) intake (DMI) was 61 g
      DM/kg0.75 BW (+/-10) and correlated negatively to dietary ME content (p = .009; r
      = -.596). Apparently, feed intake was regulated by energetic satiety and not by
      physical properties of forage. A negative correlation between produce proportion
      and DMI (p = .002; r = -.676) led to the assumption of a low ruminal pH in
      giraffes fed high proportions of produce. Increasing dietary forage proportions
      led to an increasing duration of feed intake (p = .045; r = .477) and decreasing
      occurrence of oral stereotypies (p = .047; r = -.474). The weighted average
      faecal particle size was larger than reported for free-ranging giraffes, but no
      relation to ration characteristics among the facilities existed. The abrasiveness
      of rations was not excessive, as contents of silicate in faeces were similar to
      values from the wild. Body condition was generally acceptable, but there was no
      evident relation to ration characteristics. The capacity to self-regulate DM and
      ME intakes with lucerne hay may work at higher forage proportions than often
      assumed for captive giraffes. Rations with less energetic density can result in a
      greater DMI, including maximisation of forage intake and reduction of oral
      stereotypies.

PMID- 29024064
TI  - Physiological and health-related response of broiler chickens fed diets
      containing raw, full-fat soya bean meal supplemented with microbial protease.
AB  - A 2 * 3 factorial study (protease: 0 or 1,5000 PROT/kg and raw full-fat soya bean
      meal [RSBM] replacing the commercial SBM at 0, 45 and 75 g/kg of diet) was
      conducted to examine the performance of broilers. Phytase (2000 FYT/kg) was
      uniformly added to each diet, each also replicated six times, with eight birds
      per replicate. Birds were raised in climate-controlled rooms using sawdust as the
      bedding material and offered starter, grower and finisher diets. Feed intake (FI)
      and body weight gain (BWG) were reduced (p < .05) due to increasing levels of
      RSBM, but feed conversion ratio (FCR; 0-35 days) was unaffected. Over the first
      24 days, neither RSBM nor protease supplementation affected (p > .05) mortality,
      footpad dermatitis or intestinal lesions in birds. At day 24, the weight, length,
      width and strength of tibia bone were reduced in chickens that received an
      elevated level of RSBM (75 g/kg of diet), but this was not significant at day 35.
      At day 24 (p < .05) and 35 (p < .01), Ca concentration in the litter was reduced
      when the RSBM level was increased in the diet, but P content was not affected. On
      days 24 (p < .05) and 35 (p < .01), the N content in litter was also increased
      with increase in dietary RSBM. Protease supplementation increased (p < .05) the
      uric acid concentration in the litter (at day 35), but the reverse was the case
      for ammonia concentration. Overall, the results of this study indicate that there
      are no major health-related risks, associated with the replacement of commercial
      SBM with RSBM (<=25%) in broiler diets.

PMID- 29024065
TI  - 2D Organic Materials for Optoelectronic Applications.
AB  - The remarkable merits of 2D materials with atomically thin structures and
      optoelectronic attributes have inspired great interest in integrating 2D
      materials into electronics and optoelectronics. Moreover, as an emerging field in
      the 2D-materials family, assembly of organic nanostructures into 2D forms offers
      the advantages of molecular diversity, intrinsic flexibility, ease of processing,
      light weight, and so on, providing an exciting prospect for optoelectronic
      applications. Herein, the applications of organic 2D materials for optoelectronic
      devices are a main focus. Material examples include 2D, organic, crystalline,
      small molecules, polymers, self-assembly monolayers, and covalent organic
      frameworks. The protocols for 2D-organic-crystal-fabrication and -patterning
      techniques are briefly discussed, then applications in optoelectronic devices are
      introduced in detail. Overall, an introduction to what is known and suggestions
      for the potential of many exciting developments are presented.

PMID- 29024066
TI  - A comparison of exogenous and endogenous CEST MRI methods for evaluating in vivo
      pH.
AB  - PURPOSE: Extracellular pH (pHe) is an important biomarker for cancer cell
      metabolism. Acido-chemical exchange saturation transfer (CEST) MRI uses the
      contrast agent iopamidol to create spatial maps of pHe. Measurements of amide
      proton transfer exchange rates (kex ) from endogenous CEST MRI were compared to
      pHe measurements by exogenous acido-CEST MRI to determine whether endogenous kex
      could be used as a proxy for pHe measurements. METHODS: Spatial maps of pHe and
      kex were obtained using exogenous acidoCEST MRI and an endogenous CEST MRI
      analyzed with the omega plot method, respectively, to evaluate mouse kidney, a
      flank tumor model, and a spontaneous lung tumor model. The pHe and kex results
      were evaluated using pixelwise comparisons. RESULTS: The kex values obtained from
      endogenous CEST measurements did not correlate with the pHe results from
      exogenous CEST measurements. The kex measurements were limited to fewer pixels
      and had a limited dynamic range relative to pHe measurements. CONCLUSION:
      Measurements of kex with endogenous CEST MRI cannot substitute for pHe
      measurements with acidoCEST MRI. Whereas endogenous CEST MRI may still have good
      utility for evaluating some specific pathologies, exogenous acido-CEST MRI is
      more appropriate when evaluating pathologies based on pHe values. Magn Reson Med
      79:2766-2772, 2018. (c) 2017 International Society for Magnetic Resonance in
      Medicine.

PMID- 29024068
TI  - Autosomal recessive epidermolysis bullosa simplex due to KRT14 mutation: two
      large Palestinian families and literature review.

PMID- 29024069
TI  - Functional analysis of ESM1 by siRNA knockdown in primary and metastatic head and
      neck cancer cells.
AB  - BACKGROUND: Genetic factors play a large role in cancer, and thus, there is a
      great desire to understand the effects of different genes in cancer and to also
      develop gene therapy for better treatments. Therefore, the development of
      alternative diagnosis and therapy modalities is of utmost importance. The aim of
      our study was to illuminate the role of ESM1 (endothelial cell-specific molecule
      1, also known as Endocan) in proliferation and migration of head and neck cancer,
      thus helping to pave the way for new treatment modalities and predictive
      biomarkers. METHODS: ESM1 expression was shown with immunofluorescence assay
      using confocal laser scanning microscope in primary and metastatic head and neck
      cancer cells. ESM1 expression was knocked down by RNA interference in head and
      neck cancer cells. Knockdown efficiency was evaluated by quantitative real-time
      RT-PCR and Western blot. Cell proliferation and migration assays were performed
      by xCELLigence real-time cell analysis system. RESULTS: Immunofluorescence assay
      showed nuclear localization and high expression of ESM1 in primary and metastatic
      head and neck cancer cells. ESM1 mRNA and protein levels were significantly
      decreased in ESM1-knockdown cells compared to control. ESM1-knockdown cells
      showed reduced proliferation and migration activity when compared to control
      cells. CONCLUSION: These findings suggest that ESM1 has roles on proliferation
      and migration of head and neck cancer cells.

PMID- 29024067
TI  - Evaluation of multiplex real-time PCR for identifying dermatophytes in clinical
      samples-A multicentre study.
AB  - The gold-standard method for dermatophyte identification involves direct
      microscopy and culture, which have inherent shortcomings. Only few molecular
      methods have been standardised for routine clinical work. This study aimed to
      develop and test a platform for identifying the most common dermatophytes in
      Israel using multiplex real-time polymerase chain reaction (RT-PCR). Specific
      primers were designed for the multiplex system (LightCycler 480) according to
      known cultures and validated by reference isolates. The dermatophyte detection
      rate was compared to smear and culture in 223 clinical samples obtained from a
      tertiary medical centre. Inconsistencies between methods were evaluated by
      sequencing. The RT-PCR was further evaluated in 200 community-based samples
      obtained from a health maintenance organisation and 103 military-personnel-based
      samples analysed at a central laboratory. In hospital-based clinical samples,
      complete concordance between methods was observed in 190 samples (85%; Kappa =
      0.69). In most cases of non-concordance, sequencing was consistent with RT-PCR
      results. RT-PCR correctly identified all smear- and culture-positive cases in
      community and military-personnel samples. The results were available within 4
      hours. The multiplex RT-PCR platform is a rapid and efficient method for
      identifying dermatophyte species in clinical samples and may serve as a first
      step in the diagnostic algorithm of superficial fungal infections.

PMID- 29024070
TI  - The tyranny of numbers, large and small.

PMID- 29024071
TI  - An unjustified benefit: immortal time bias in the analysis of time-dependent
      events.
AB  - Immortal time bias is a problem arising from methodologically wrong analyses of
      time-dependent events in survival analyses. We illustrate the problem by analysis
      of a kidney transplantation study. Following patients from transplantation to
      death, groups defined by the occurrence or nonoccurrence of graft failure during
      follow-up seemingly had equal overall mortality. Such naive analysis assumes that
      patients were assigned to the two groups at time of transplantation, which
      actually are a consequence of occurrence of a time-dependent event later during
      follow-up. We introduce landmark analysis as the method of choice to avoid
      immortal time bias. Landmark analysis splits the follow-up time at a common,
      prespecified time point, the so-called landmark. Groups are then defined by time
      dependent events having occurred before the landmark, and outcome events are only
      considered if occurring after the landmark. Landmark analysis can be easily
      implemented with common statistical software. In our kidney transplantation
      example, landmark analyses with landmarks set at 30 and 60 months clearly
      identified graft failure as a risk factor for overall mortality. We give further
      typical examples from transplantation research and discuss strengths and
      limitations of landmark analysis and other methods to address immortal time bias
      such as Cox regression with time-dependent covariables.

PMID- 29024072
TI  - Structurally Deformed MoS2 for Electrochemically Stable, Thermally Resistant, and
      Highly Efficient Hydrogen Evolution Reaction.
AB  - The emerging molybdenum disulfide (MoS2 ) offers intriguing possibilities for
      realizing a transformative new catalyst for driving the hydrogen evolution
      reaction (HER). However, the trade-off between catalytic activity and long-term
      stability represents a formidable challenge and has not been extensively
      addressed. This study reports that metastable and temperature-sensitive
      chemically exfoliated MoS2 (ce-MoS2 ) can be made into electrochemically stable
      (5000 cycles), and thermally robust (300  degrees C) while maintaining synthetic
      scalability and excellent catalytic activity through physical-transformation into
      3D structurally deformed nanostructures. The dimensional transition enabled by a
      high throughput electrohydrodynamic process provides highly accessible, and
      electrochemically active surface area and facilitates efficient transport across
      various interfaces. Meanwhile, the hierarchically strained morphology is found to
      improve electronic coupling between active sites and current collecting
      substrates without the need for selective engineering the electronically
      heterogeneous interfaces. Specifically, the synergistic combination of high
      strain load stemmed from capillarity-induced-self-crumpling and sulfur (S)
      vacancies intrinsic to chemical exfoliation enables simultaneous modulation of
      active site density and intrinsic HER activity regardless of continuous operation
      or elevated temperature. These results provide new insights into how catalytic
      activity, electrochemical-, and thermal stability can be concurrently enhanced
      through the physical transformation that is reminiscent of nature, in which
      properties of biological materials emerge from evolved dimensional transitions.

PMID- 29024073
TI  - Developmental stage influences chromosome segregation patterns and arrangement in
      the extremely polyploid, giant bacterium Epulopiscium sp. type B.
AB  - Few studies have described chromosomal dynamics in bacterial cells with more than
      two complete chromosome copies or described changes with respect to development
      in polyploid cells. We examined the arrangement of chromosomal loci in the very
      large, highly polyploid, uncultivated intestinal symbiont Epulopiscium sp. type B
      using fluorescent in situ hybridization. We found that in new offspring,
      chromosome replication origins (oriCs) are arranged in a three-dimensional array
      throughout the cytoplasm. As development progresses, most oriCs become
      peripherally located. Siblings within a mother cell have similar numbers of
      oriCs. When chromosome orientation was assessed in situ by labeling two
      chromosomal regions, no specific pattern was detected. The Epulopiscium genome
      codes for many of the conserved positional guide proteins used for chromosome
      segregation in bacteria. Based on this study, we present a model that conserved
      chromosomal maintenance proteins, combined with entropic demixing, provide the
      forces necessary for distributing oriCs. Without the positional regulation
      afforded by radial confinement, chromosomes are more randomly oriented in
      Epulopiscium than in most small rod-shaped cells. Furthermore, we suggest that
      the random orientation of individual chromosomes in large polyploid cells would
      not hamper reproductive success as it would in smaller cells with more limited
      genomic resources.

PMID- 29024074
TI  - Comparison of subjective wellbeing in substance users and the parents or partners
      of substance users.
AB  - INTRODUCTION AND AIMS: There is growing interest in the impact of substance use
      on both the individual consumer's subjective wellbeing (SWB) and the reduced SWB
      of those closely connected to him or her. The study aimed to compare SWB among
      substance users ('consumers') and the parents or partners affected by another's
      substance use, and to evaluate the effect of counselling on changed SWB to 6
      months. DESIGN AND METHODS: The study used longitudinal data from a not-for
      profit treatment service based in Perth, Australia. Subjective wellbeing was
      assessed with the Personal Wellbeing Index (PWI) at baseline and 6 months. Data
      were compared to national norms (mean 75.97) with one sample t tests. Change in
      PWI scores was assessed with generalised linear mixed models, controlling for
      age, gender, group (consumers versus parents or partners), psychological distress
      (Kessler-10) and social connectedness (Lubben). RESULTS: Of 220 participants, 136
      (62%) were consumers and 84 (38%) were parents or partners. At 6 months 123 (56%)
      were re-interviewed. At baseline, both consumers (mean 53.7) and parents or
      partners (mean 66.1) had significantly lower PWI scores than national norms. At 6
      months, only the substance users' PWI scores remained significantly lower (mean
      67.8). Subjective wellbeing significantly increased with time (beta = 5.52; 95%
      confidence interval 3.15, 7.90), with no significant time by group interaction.
      DISCUSSION AND CONCLUSIONS: Both groups showed significant decrements in SWB
      compared with the general population but with improvements over the study period.
      However, the lack of a control group prevents definitive assertions on causality
      for improved SWB.

PMID- 29024075
TI  - Hollow Co3 O4 Nanosphere Embedded in Carbon Arrays for Stable and Flexible Solid
      State Zinc-Air Batteries.
AB  - Highly active and durable air cathodes to catalyze both the oxygen evolution
      reaction (OER) and oxygen reduction reaction (ORR) are urgently required for
      rechargeable metal-air batteries. In this work, an efficient bifunctional oxygen
      catalyst comprising hollow Co3 O4 nanospheres embedded in nitrogen-doped carbon
      nanowall arrays on flexible carbon cloth (NC-Co3 O4 /CC) is reported. The
      hierarchical structure is facilely derived from a metal-organic framework
      precursor. A carbon onion coating constrains the Kirkendall effect to promote the
      conversion of the Co nanoparticles into irregular hollow oxide nanospheres with a
      fine scale nanograin structure, which enables promising catalytic properties
      toward both OER and ORR. The integrated NC-Co3 O4 /CC can be used as an additive
      free air cathode for flexible all-solid-state zinc-air batteries, which present
      high open circuit potential (1.44 V), high capacity (387.2 mAh g-1 , based on the
      total mass of Zn and catalysts), excellent cycling stability and mechanical
      flexibility, significantly outperforming Pt- and Ir-based zinc-air batteries.

PMID- 29024076
TI  - Imbedded Nanocrystals of CsPbBr3 in Cs4 PbBr6 : Kinetics, Enhanced Oscillator
      Strength, and Application in Light-Emitting Diodes.
AB  - Solution-grown films of CsPbBr3 nanocrystals imbedded in Cs4 PbBr6 are
      incorporated as the recombination layer in light-emitting diode (LED) structures.
      The kinetics at high carrier density of pure (extended) CsPbBr3 and the
      nanoinclusion composite are measured and analyzed, indicating second-order
      kinetics in extended and mainly first-order kinetics in the confined CsPbBr3 ,
      respectively. Analysis of absorption strength of this all-perovskite, all
      inorganic imbedded nanocrystal composite relative to pure CsPbBr3 indicates
      enhanced oscillator strength consistent with earlier published attribution of the
      sub-nanosecond exciton radiative lifetime in nanoprecipitates of CsPbBr3 in melt
      grown CsBr host crystals and CsPbBr3 evaporated films.

PMID- 29024077
TI  - Tree-Inspired Design for High-Efficiency Water Extraction.
AB  - The solar steam process, akin to the natural water cycle, is considered to be an
      attractive approach to address water scarcity issues globally. However, water
      extraction from groundwater, for example, has not been demonstrated using these
      existing technologies. Additionally, there are major unaddressed challenges in
      extracting potable water from seawater including salt accumulation and long-term
      evaporation stability, which warrant further investigation. Herein, a high
      performance solar steam device composed entirely of natural wood is reported. The
      pristine, natural wood is cut along the transverse direction and the top surface
      is carbonized to create a unique bilayer structure. This tree-inspired design
      offers distinct advantages for water extraction, including rapid water transport
      and evaporation in the mesoporous wood, high light absorption (~99%) within the
      surface carbonized open wood channels, a low thermal conductivity to avoid
      thermal loss, and cost effectiveness. The device also exhibits long-term
      stability in seawater without salt accumulation as well as high performance for
      underground water extraction. The tree-inspired design offers an inexpensive and
      scalable solar energy harvesting and steam generation technology that can provide
      clean water globally, especially for rural or remote areas where water is not
      only scarce but also limited by water extraction materials and methods.

PMID- 29024078
TI  - Fruit intake reduces the onset of respiratory allergic symptoms in
      schoolchildren.
AB  - BACKGROUND: Previous studies have shown that dietary pattern is associated with
      allergy prevention. METHODS: We conducted a prospective cohort study on all
      primary schools in Omihachiman City, Shiga Prefecture, Japan. Questionnaires
      regarding allergic symptoms and diet were distributed to the parents of all 759 7
      year-old schoolchildren for 4 consecutive years, from 2011 to 2014. Specific
      immunoglobulin E to inhalant allergens was measured at 10 years of age.
      Participants were then categorized as low, medium, or high intake during the
      study period for four food groups (fruits, vegetables, fish, and beans). Logistic
      regression analysis was performed to estimate odds ratios and 95% confidence
      intervals. RESULTS: A total of 520 children (68.5%) whose parents responded to
      the questionnaires all 4 years were included in the analysis. The prevalence of
      asthma, rhinitis, and any allergic symptoms at age 10 was significantly decreased
      with increases in fruit intake. In addition, the onset of any allergic symptoms
      during the study period was significantly decreased with increases in fruit
      intake (33.3%, 28.3%, and 14.3% in children with low, medium, and high fruit
      intake, respectively; P for trend =.01). The sensitization rate to ragweed at age
      10 was significantly decreased with increases in fruit intake (P for trend
      =.046). No significant effect was observed for the other three food groups,
      except for the association between fish intake and new-onset asthma symptoms.
      CONCLUSIONS: These findings suggest that higher intake of fruit can help prevent
      respiratory allergic symptoms in schoolchildren.

PMID- 29024079
TI  - The preadolescent acne microbiome: A prospective, randomized, pilot study
      investigating characterization and effects of acne therapy.
AB  - BACKGROUND/OBJECTIVES: Acne, a common pediatric disease, tends to be more
      comedonal in preadolescents, whereas older individuals are more likely to have
      inflammatory lesions in addition to comedones. Thus the microbiome of
      preadolescents may be different. In this pilot study we aimed to characterize the
      preadolescent acne microbiome, compare the microbiome in preadolescents with and
      without acne, and investigate changes in the microbiome after topical treatment
      with benzoyl peroxide or a retinoid in a small cohort of preadolescents. METHODS:
      Participants were 7-10 years of age with (intervention group) or without (control
      group) acne and were recruited during routine outpatient dermatology visits.
      Baseline questionnaires, physical examination, and pore strip application were
      performed for all participants. Intervention group participants were randomized
      to receive topical therapy with benzoyl peroxide 5% gel or cream or tretinoin
      0.025% cream. Participants with acne were followed up 8-10 weeks later and pore
      strip application was repeated. RESULTS: Preadolescents with acne were colonized
      with a greater diversity of cutaneous bacteria than controls and the most
      commonly identified bacterium was Streptococcus. The number of bacterial species
      and phylogenetic diversity decreased after treatment with benzoyl peroxide and
      tretinoin. CONCLUSION: The predominant bacteria in microbiome studies of adult
      acne is Propionibacterium, whereas in this pediatric population we saw a lot of
      Streptococcus bacteria. After treatment, the microbiomes of intervention group
      participants more closely resembled those of control group participants.

PMID- 29024080
TI  - Randomized comparison of balloon aortic valvuloplasty performed with or without
      rapid cardiac pacing: The pacing versus no pacing (PNP) study.
AB  - OBJECTIVES: To compare the effectiveness and safety of balloon aortic
      valvuloplasty (BAV) performed with or without rapid ventricular pacing (RP).
      BACKGROUND: BAV technique is poorly standardized. METHODS: One hundred
      consecutive patients were randomly assigned 1:1 between BAV performed with or
      without RP. Exclusion criteria were an immediate indication for surgical or
      transcatheter aortic valve replacement, presentation in cardiogenic shock or
      pulmonary edema refractory to medical stabilization. RESULTS: There were 51
      patients in the BAV group performed with RP, 49 in the BAV group without RP
      (noRP). Procedural success (50% hemodynamic gradient reduction) was achieved in
      37.3% and 55.1%, respectively (P = 0.16). Fewer people in the noRP group
      complained of poor tolerance to the procedure (16% vs 41%). The primary efficacy
      endpoint, a 50% reduction in the mean echocardiographic trans-aortic gradient,
      was met in 21/49 patients in the noRP group compared to 20/51 in the RP (42.9% vs
      39.2%; P = 0.84). No significant difference between the groups was observed in
      the primary safety endpoint, a 30-day composite of death, myocardial infarction,
      stroke, acute aortic regurgitation, and BARC bleeding >=3 (8.2% noRP vs 13.7%; P
      = 0.53). The noRP group required fewer bailout temporary pacemakers (P = 0.048)
      and had a lower incidence of moderate/severe renal function worsening (4.1% vs
      17.6%; P = 0.052). CONCLUSIONS: Rapid ventricular pacing did not influence BAV
      efficacy or safety and tolerance was slightly worse.

PMID- 29024081
TI  - The effect of Rosa (L. Rosa canina) on the incidence of urinary tract infection
      in the puerperium: A randomized placebo-controlled trial.
AB  - Urinary tract infection (UTI) is an infection that can occur in any area of the
      urinary tract which is characterized by a positive urine culture (U/C). The risk
      of UTI following cesarean section (CS) increases due to procedures such as
      catheterization. In vitro studies have demonstrated the effect of Rosa canina
      fruit in preventing Escherichia coli growth. This study was conducted to
      determine the effect of R. canina fruit in preventing the incidence of UTI in
      women following CS. This triple-blind randomized clinical trial was conducted in
      2016 on 400 women following CS with negative U/C in Alzahra and Taleghani
      educational hospitals in the city of Tabriz-Iran. Participants were assigned into
      two groups of 200 women using block randomization. Each group received a twice
      daily dose of 500 mg capsules containing R. canina or placebo from the second day
      after CS for 20 days. Women were assessed by U/C on the 7th-10th and 20th days
      following CS. UTI was significantly lower in the intervention group compared with
      the control in the follow-ups conducted on the 7th-10th days (odds ratio = 0.22;
      confidence interval 95% [0.07, 0.67]; p = .006) and 20th day (odds ratio = 0.32;
      confidence interval 95% [0.14, 0.75]; p = .008). But the incidence of cystitis in
      the two groups was not statistically significant (p > .05). R. canina fruit
      capsules were able to reduce the incidence of UTI after CS. Thus, it is likely
      that administration of this medication can promote maternal health following CS.

PMID- 29024082
TI  - Paraneoplastic bullous pemphigoid associated with penile squamous cell carcinoma.

PMID- 29024083
TI  - Stimulated Transitions of Directed Nonequilibrium Self-Assemblies.
AB  - Near-equilibrium stimulus-responsive polymers have been used extensively to
      introduce morphological variations in dependence of adaptable conditions. Far
      less-well studied are triggered transformations at constant conditions. These
      require the involvement of metastable states, which are either able to approach
      the equilibrium state after deviation from metastability or can be frozen on
      returning from nonequilibrium to equilibrium. Such functional nonequilibrium
      macromolecular systems hold great promise for on-demand transformations, which
      result in substantial changes in their material properties, as seen for triggered
      gelations. Herein, a diblock copolymer system consisting of a hydrophilic block
      and a block that is responsive to both pressure and temperature, is introduced.
      This species demonstrates various micellar transformations upon leaving
      equilibrium/nonequilibrium states, which are triggered by a temperature
      deflection or a temporary application of hydrostatic pressure.

PMID- 29024085
TI  - Structure Determination, Conformational Flexibility, Internal Dynamics, and
      Chiral Analysis of Pulegone and Its Complex with Water.
AB  - In the current work we present a detailed analysis of the chiral molecule
      pulegone, which is a constituent of essential oils, using broadband rotational
      spectroscopy. Two conformers are observed under the cold conditions of a
      molecular jet. We report an accurate experimentally determined structure for the
      lowest energy conformer. For both conformers, a characteristic splitting pattern
      is observed in the spectrum, resulting from the internal rotation of the two non
      equivalent methyl groups situated in the isopropylidene side chain. The
      determined energy barriers are 1.961911(46) kJ mol-1 and 6.3617(12) kJ mol-1 for
      one conformer, and 1.96094(74) kJ mol-1 and 6.705(44) kJ mol-1 for the other one.
      Moreover, a cluster of the lowest energy conformer with one water molecule is
      reported. The water molecule locks one of the methyl groups by means of a
      hydrogen bond and some secondary interactions, so that we only observe internal
      rotation splittings from the other methyl group with an internal rotation barrier
      of 2.01013(38) kJ mol-1 . Additionally, the chirality-sensitive microwave three
      wave mixing technique is applied for the differentiation between the enantiomers,
      which can become of further use for the analysis of essential oils.

PMID- 29024084
TI  - Characterization of and lipopolysaccharide binding to the E. coli LptC protein
      dimer.
AB  - Lipopolysaccharide (LPS, endotoxin) is the major component of the outer leaflet
      of the outer membrane of Gram-negative bacteria such as Escherichia coli and
      Salmonella typhimurium. LPS is a large lipid containing several acyl chains as
      its hydrophobic base and numerous sugars as its hydrophilic core and O-antigen
      domains, and is an essential element of the organisms' natural defenses in
      adverse environmental conditions. LptC is one of seven members of the
      lipopolysaccharide transport (Lpt) protein family that functions to transport LPS
      from the inner membrane (IM) to the outer leaflet of the outer membrane of the
      bacterium. LptC is anchored to the IM and associated with the IM LptFGB2 complex.
      It is hypothesized that LPS binds to LptC at the IM, transfers to LptA to cross
      the periplasm, and is inserted by LptDE into the outer leaflet of the outer
      membrane. The studies described here comprehensively characterize and quantitate
      the binding of LPS to LptC. Site-directed spin labeling electron paramagnetic
      resonance spectroscopy was utilized to characterize the LptC dimer in solution
      and monitor spin label mobility changes at 10 sites across the protein upon
      addition of exogenous LPS. The results indicate that soluble LptC forms
      concentration-independent N-terminal dimers in solution, LptA binding does not
      change the conformation of the LptC dimer nor appreciably disrupt the LptC dimer
      in vitro, and LPS binding affects the entire LptC protein, with the center and C
      terminal regions showing a greater affinity for LPS than the N-terminal domain,
      which has similar dissociation constants to LptA.

PMID- 29024086
TI  - Combined endogenous MR biomarkers to predict basal tumor oxygenation and response
      to hyperoxic challenge.
AB  - Hypoxia is a common feature of solid tumors, which translates into increased
      angiogenesis, malignant phenotype cell selection, change in gene expression and
      greater resistance to radiotherapy and chemotherapy. Therefore, there is a need
      for markers of hypoxia to stratify patients, in order to personalize treatment to
      improve therapeutic outcome. However, no modality has yet been validated for the
      screening of hypoxia in routine clinical practice. Magnetic resonance imaging
      (MRI) R1 and R2 * relaxation parameters are sensitive to tissue oxygenation: R1
      is sensitive to dissolved oxygen and R2 * is sensitive to intravascular
      deoxyhemoglobin content. Two rat tumor models with distinct levels of hypoxia, 9L
      glioma and rhabdomyosarcoma, were imaged for R1 and R2 * under air and carbogen
      (95% O2 and 5% CO2 ) breathing conditions. It was observed that the basal tumor
      oxygenation level had an impact on the amplitude of response to carbogen in the
      vascular compartment (R2 *), but not in the tissue compartment (R1 ). In
      addition, the change in tissue oxygenation estimated by DeltaR1 correlated with
      the change in vascular oxygenation estimated by DeltaR2 *, which is consistent
      with an increase in oxygen supply generating an elevated tumor pO2 . At the intra
      tumoral level, we identified four types of voxel to which a hypoxic feature was
      attributed (mild hypoxia, severe hypoxia, normoxia and vascular steal), depending
      on the carbogen-induced change in R1 and R2 * values for each voxel. The results
      showed that 9L-gliomas present more normoxic fractions, whereas rhabdomyosarcomas
      present more hypoxic fractions, which is in accordance with a previous study
      using 18 F-fluoroazomycin arabinoside (18 F-FAZA) and electron paramagnetic
      resonance (EPR) oximetry. The response of the combined endogenous MRI contrasts
      to carbogen challenge could be a useful tool to predict different tumor hypoxic
      fractions.

PMID- 29024087
TI  - Chemical Intercalation of Topological Insulator Grid Nanostructures for High
      Performance Transparent Electrodes.
AB  - 2D layered nanomaterials with strong covalent bonding within layers and weak van
      der Waals' interactions between layers have attracted tremendous interest in
      recent years. Layered Bi2 Se3 is a representative topological insulator material
      in this family, which holds promise for exploration of the fundamental physics
      and practical applications such as transparent electrode. Here, a simultaneous
      enhancement of optical transmittancy and electrical conductivity in Bi2 Se3 grid
      electrodes by copper-atom intercalation is presented. These Cu-intercalated 2D
      Bi2 Se3 electrodes exhibit high uniformity over large area and excellent
      stabilities to environmental perturbations, such as UV light, thermal
      fluctuation, and mechanical distortion. Remarkably, by intercalating a high
      density of copper atoms, the electrical and optical performance of Bi2 Se3 grid
      electrodes is greatly improved from 900 Omega sq-1 , 68% to 300 Omega sq-1 , 82%
      in the visible range; with better performance of 300 Omega sq-1 , 91% achieved in
      the near-infrared region. These unique properties of Cu-intercalated topological
      insulator grid nanostructures may boost their potential applications in high
      performance optoelectronics, especially for infrared optoelectronic devices.

PMID- 29024088
TI  - Parental-genome dosage effects on the transcriptome of F1 hybrid triploid embryos
      of Arabidopsis thaliana.
AB  - Genomic imprinting in the seed endosperm could be due to unequal parental-genome
      contribution effects in triploid endosperm tissue that trigger parent-of-origin
      specific activation and/or silencing of loci prone to genomic imprinting. To
      determine whether genomic imprinting is triggered by unequal parental-genome
      contribution effects, we generated a whole-genome transcriptome dataset of F1
      hybrid triploid embryos (as mimics of F1 hybrid triploid endosperm). For the vast
      majority of genes, the parental contributions to their expression levels in the
      F1 triploid hybrid embryos follow a biallelic and linear expression pattern.
      While allele-specific expression (ASE) bias was detected, such effects were
      predominantly parent-of-origin independent. We demonstrate that genomic
      imprinting is largely absent from F1 triploid embryos, strongly suggesting that
      neither triploidy nor unequal parental-genome contribution are key triggers of
      genomic imprinting in plants. However, extensive parental-genome dosage effects
      on gene expression were observed between the reciprocal F1 hybrid embryos,
      particularly for genes involved in defence response and nutrient reservoir
      activity, potentially leading to the seed size differences between reciprocal
      triploids. We further determined that unequal parental-genome contribution in F1
      triploids can lead to overexpression effects that are parent-of-origin dependent,
      and which are not observed in diploid or tetraploid embryos in which the parental
      genome dosage is balanced. Overall, our study demonstrates that neither triploidy
      nor unequal parental-genome contribution is sufficient to trigger imprinting in
      plant tissues, suggesting that genomic imprinting is an intrinsic and unique
      feature of the triploid seed endosperm.

PMID- 29024089
TI  - Macronutrient intake of dogs, self-selecting diets varying in composition offered
      ad libitum.
AB  - The diet of the domestic dog has changed significantly from that of its wolf
      ancestor, with to date only two studies having examined macronutrient self
      selection in dogs. Whilst the first focused solely on protein intake, determining
      an intake of 30% metabolisable energy (ME), the second investigated dietary
      protein, fat and carbohydrate (PFC), indicating an intake ratio of 30:63:7% by
      energy. This study's aim was to further elucidate macronutrient intake by
      providing greater macronutrient range, energy content, and to investigate over a
      longer duration than previous studies. Fifteen adult dogs were given access to
      three wet diets providing 500% of daily ME, twice daily over 10 days. The diets
      were nutritionally complete and formulated using the same four ingredients in
      different proportions to supply high levels of protein (58% ME), fat (86% ME) or
      carbohydrate (54% ME). Overall fat and carbohydrate consumption significantly
      declined from 6,382 to 917 kcals per day (p < 0.001) and 553 to 214 kcals day-1
      (p < .01) respectively. Protein intake, however, remained constant over the study
      and ranged from 4,786 to 4,156 kcals day-1 . Such results impacted on percentage
      total energy intake, with fat decreasing from 68% to 52% (p < .001) and protein
      increasing from 29% to 44% (p < .01). Our findings suggest that dogs still
      possess a "feast or famine" mentality, wherein energy dense fat is prioritised
      over protein initially. With continued feeding over 10 days, a transition to a
      more balanced energy contribution from both macronutrients is evident. The study
      also shows that given the option, dogs do not select carbohydrate to be a
      significant portion of the diet. The health implications of such dietary
      selection are of interest.

PMID- 29024090
TI  - Reactivity of 3-Oxo-beta-lactams with Respect to Primary Amines-An Experimental
      and Computational Approach.
AB  - The reactivity of 3-oxo-beta-lactams with respect to primary amines was
      investigated in depth. Depending on the specific azetidin-2-one C4 substituent,
      this reaction was shown to selectively produce 3-imino-beta-lactams (through
      dehydration), alpha-aminoamides (through CO elimination), or ethanediamides
      (through an unprecedented C3-C4 ring opening). In addition to the experimental
      results, the mechanisms and factors governing these peculiar transformations were
      also examined and elucidated by means of DFT calculations.

PMID- 29024091
TI  - Protective effect of cinnamic acid in endotoxin-poisoned mice.
AB  - In this work, we aimed to evaluate the protective effect of cinnamic acid (CD) on
      lipopolysaccharide (LPS; Escherichia coli 055:B5)-induced endotoxin-poisoned mice
      and clarify the underlying mechanisms. The mice were administrated CD 5 d before
      15 mg/kg LPS challenge. 12 hr later, thymus was separated for determination of
      thymus indexes. Lung and spleen tissues were collected for histologic examination
      and the wet/dry weight ratio of lung was calculated, and serum was acquired for
      tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-18, and IL-1beta
      measurement. Moreover, the expression of NOD-like receptor (NLR) family, pyrin
      domain-containing 3 (NLRP3) inflammasome was determined in lung. CD increased the
      thymus indexes and decreased lung wet/dry weight ratio. In addition, CD improved
      the lung and spleen histopathological changes induced by LPS and decreased the
      number of neutrophils in lung tissues. CD also inhibited the pro-inflammatory
      cytokines (TNF-alpha, IL-18, and IL-1beta) production in serum. Furthermore, CD
      suppressed the LPS-induced NLRP3, Caspase-1, and IL-1beta mRNA expression in
      lung, as well as the expression of NLRP3 and Caspase-1 (p20) protein. CD may have
      protective effects in endotoxin-poisoned mice via inhibiting the activation of
      NLRP3 inflammasome, and can be considered as a potential therapeutic candidate
      for diseases involved in endotoxin poisoning such as sepsis.

PMID- 29024092
TI  - Pharmaceutical opioid use and harm in Australia: The need for proactive and
      preventative responses.
AB  - There are parallels between the North American experience of escalating
      pharmaceutical opioid utilisation and harm and the trends being observed in
      Australia. In Australia, opioid utilisation has increased dramatically over the
      past two decades. There have been significant shifts away from the predominant
      prescribing of 'weak' and short-acting opioids, to 'strong' and long-acting
      opioids, for an increasing range of chronic pain indications. In concordance with
      escalating use, Australia is experiencing increases in opioid-related hospital
      admissions and overdose, as well as opioid dependence and treatment seeking.
      Despite increasing concern regarding pharmaceutical opioid use and harms in
      Australia, responses have been limited. There have been no recent changes in
      regulatory systems for prescription-only pharmaceutical opioids, opioid
      prescribing guidelines, limits on doctors' prescribing, monitoring of patient or
      doctor access to opioids, or in access to medicines via public subsidy.
      Potentially abuse-deterrent opioid formulations have entered the Australian
      market, with studies suggesting that these formulations are less likely to be
      tampered with by people who inject drugs; but to date, there have been limited
      impacts on opioid utilisation and harm. Additional strategies may include
      enhancing access to effective approaches to pain management and opioid
      dependence, and scaling-up naloxone provision. There is a unique opportunity for
      a proactive and preventative response to pharmaceutical opioids in Australia, to
      avoid experiencing the scale of problems seen elsewhere.

PMID- 29024093
TI  - Remarkably High Stability of Late Actinide Dioxide Cations: Extending Chemistry
      to Pentavalent Berkelium and Californium.
AB  - Actinyl chemistry is extended beyond Cm to BkO2+ and CfO2+ through transfer of an
      O atom from NO2 to BkO+ or CfO+ , establishing a surprisingly high lower limit of
      73 kcal mol-1 for the dissociation energies, D[O-(BkO+ )] and D[O-(CfO+ )].
      CCSD(T) computations are in accord with the observed reactions, and characterize
      the newly observed dioxide ions as linear pentavalent actinyls; these being the
      first Bk and Cf species with oxidation states above IV. Computations of actinide
      dioxide cations AnO2+ for An=Pa to Lr reveal an unexpected minimum for D[O-(CmO+
      )]. For CmO2+ , and AnO2+ beyond EsO2+ , the most stable structure has side-on
      bonded eta2 -(O2 ), as AnIII peroxides for An=Cm and Lr, and as AnII superoxides
      for An=Fm, Md, and No. It is predicted that the most stable structure of EsO2+ is
      linear [O=EsV =O]+ , einsteinyl, and that FmO2+ and MdO2+ , like CmO2+ , also
      have actinyl(V) structures as local energy minima. The results expand actinide
      oxidation state chemistry, the realm of the distinctive actinyl moiety, and the
      non-periodic character towards the end of the periodic table.

PMID- 29024095
TI  - Trivalent Lewis Acidic Cations Govern the Electronic Properties and Stability of
      Heterobimetallic Complexes of Nickel.
AB  - Assembly of heterobimetallic complexes is synthetically challenging due to the
      propensity of ditopic ligands to bind metals unselectively. Here, we employ a
      novel divergent approach for selective preparation of a variety of bimetallic
      complexes within a ditopic macrocyclic ligand platform. In our approach, nickel
      is readily coordinated to a Schiff base cavity, and then a range of redox
      inactive cations (M=Na+ , Ca2+ , Nd3+ , and Y3+ ) are installed in a pendant
      crown-ether-like site. This modular strategy allows access to complexes with the
      highly Lewis acidic trivalent cations Nd3+ and Y3+ , a class of compounds that
      were previously inaccessible. Spectroscopic and electrochemical studies reveal
      wide variations in properties that are governed most strongly by the trivalent
      cations. Exposure to dimethylformamide drives loss of Nd3+ and Y3+ from the
      pendant crown-ether site, suggesting solvent effects must be carefully considered
      in future applications involving use of highly Lewis acidic metals.

PMID- 29024096
TI  - State-of-the-art immunogenicity evaluation in phase 3 confirmatory study
      (EGALITY) with etanercept biosimilar GP2015.

PMID- 29024097
TI  - Synthesis of 1,1'- and 2,2'-Bicarbazole Alkaloids by Iron(III)-Catalyzed
      Oxidative Coupling of 2- and 1-Hydroxycarbazoles.
AB  - We describe the synthesis of 1,1'- and 2,2'-bicarbazoles by oxidative
      homocoupling of 2- and 1-hydroxycarbazoles. The oxidative coupling using
      catalytic amounts of F16 PcFe can be applied to both groups of substrates.
      Although F16 PcFe generally provides the best yields for the synthesis of 1,1'
      bicarbazoles, di-tert-butyl peroxide affords better results for the 2,2'
      bicarbazoles. In our study, we have achieved the first syntheses of the
      biscarbalexines A-C, bisglybomine B, 2,2'-dihydroxy-7,7'-dimethoxy-3,3'-dimethyl
      1,1'-bicarbazole, bispyrayafoline C, and bisisomahanine. The iron-catalyzed
      coupling of koenigine led to an improved synthesis of 8,8''-biskoenigine and
      afforded an unprecedented decacylic product. Oxidative coupling of 1
      hydroxycarbazoles led to bisclausenol, and to the first total syntheses of
      bismurrayafoline B and D.

PMID- 29024099
TI  - Intrathyroidal carotid artery and nonrecurring right recurrent laryngeal nerve: A
      case report.
AB  - BACKGROUND: When performing thyroidectomy, knowledge of normal anatomy and
      variants is vital to avoid injuring nearby structures. Typically, the bilateral
      carotids course posterolateral to the thyroid gland. We describe a rare variant
      of an intrathyroidal carotid artery, not previously described in the literature.
      METHODS: A 23-year-old woman with a strong family history of thyroid cancer
      presented with a left thyroid nodule, and a fine-needle aspiration biopsy
      revealing papillary thyroid carcinoma. She underwent total thyroidectomy.
      RESULTS: Intraoperatively, the carotid was found coursing centrally through the
      right lobe parenchyma, associated with an ipsilateral nonrecurrent recurrent
      laryngeal nerve (NRLN) entering the cricothyroid joint superolaterally.
      CONCLUSION: This is, to our knowledge, the first report of such an anatomic
      variant in the medical literature. Aberrant carotid artery anatomy may
      potentially cause life-threatening surgical complications and should be
      considered preoperatively. Furthermore, recognition of concurrent recurrent
      laryngeal nerve (RLN) anomalies with vascular variations allows identification of
      nonrecurrent nerves.

PMID- 29024098
TI  - Hemin-Graphene Derivatives with Increased Peroxidase Activities Restrain Protein
      Tyrosine Nitration.
AB  - Protein tyrosine nitration is implicated in the occurrence and progression of
      pathological conditions involving free radical reactions. It is well recognized
      that hemin can catalyze protein tyrosine nitration in the presence of nitrite and
      hydrogen peroxide. Generally, the catalytic efficiency is positively correlated
      to its peroxidase activity. In this study, however, it is found that the
      efficiency of hemin in catalyzing protein tyrosine nitration is largely
      suppressed after functionalization with graphene derivatives, even though its
      peroxidase-like activity is more than quadrupled. Further studies show that the
      oxidation of tyrosine is still observed for these composites; dityrosine
      formation, however, is greatly inhibited. Furthermore, these composites also
      exhibit strong effects on the oxidation of nitrite into nitrate. Therefore, we
      propose a mechanism in which hemin-graphene derivatives facilitate the oxidation
      of tyrosine and nitrite to produce tyrosyl radicals and nitrogen dioxide radicals
      in the presence of hydrogen peroxide, but graphene interlayers serve as barriers
      that hinder radical-radical coupling reactions; consequently, protein tyrosine
      nitration is restrained. This property of hemin-graphene derivatives, by which
      they catalyze substrate oxidation but suppress radical-radical coupling
      reactions, shows their great potential in selective oxidation procedures for
      byproduct removal.

PMID- 29024100
TI  - An All-Integrated Anode via Interlinked Chemical Bonding between Double-Shelled
      Yolk-Structured Silicon and Binder for Lithium-Ion Batteries.
AB  - The concept of an all-integrated design with multifunctionalization is widely
      employed in optoelectronic devices, sensors, resonator systems, and microfluidic
      devices, resulting in benefits for many ongoing research projects. Here,
      maintaining structural/electrode stability against large volume change by means
      of an all-integrated design is realized for silicon anodes. An all-integrated
      silicon anode is achieved via multicomponent interlinking among
      carbon@void@silica@silicon (CVSS) nanospheres and cross-linked carboxymethyl
      cellulose and citric acid polymer binder (c-CMC-CA). Due to the additional
      protection from the silica layer, CVSS is superior to the carbon@void@silicon
      (CVS) electrode in terms of long-term cyclability. The as-prepared all-integrated
      CVSS electrode exhibits high mechanical strength, which can be ascribed to the
      high adhesivity and ductility of c-CMC-CA binder and the strong binding energy
      between CVSS and c-CMC-CA, as calculated based on density functional theory
      (DFT). This electrode exhibits a high reversible capacity of 1640 mA h g-1 after
      100 cycles at a current density of 1 A g-1 , high rate performance, and long-term
      cycling stability with 84.6% capacity retention after 1000 cycles at 5 A g-1 .

PMID- 29024101
TI  - Photocatalyzing CO2 to CO for Enhanced Cancer Therapy.
AB  - Continuous exposure to carbon monoxide (CO) can sensitize cancer cells to
      chemotherapy while protect normal cells from apoptosis. The Janus face of CO thus
      provides an ideal strategy for cancer therapy. Here, a photocatalytic
      nanomaterial (HisAgCCN) is introduced to transform endogenous CO2 to CO for
      improving cancer therapy in vivo. The CO production rate of HisAgCCN reaches to
      65 umol h-1 gmat-1 , which can significantly increase the cytotoxicity of
      anticancer drug (doxorubicin, DOX) by 70%. Interestingly, this study finds that
      HisAgCCN can enhance mitochondria biogenesis and aggravate oxidative stress in
      cancer cells, whereas protect normal cells from chemotherapy-induced apoptosis as
      well. Proteomics and metabolomics studies reveal that HisAgCCN can enhance
      mitochondria biogenesis and aggravate oxidative stress in cancer cells
      specifically. In vivo studies indicate that HisAgCCN/DOX combination therapy
      presents a synergetic tumor inhibition, which might provide a new direction for
      clinical cancer therapy.

PMID- 29024102
TI  - Asian Organization for Crohn's and Colitis and Asia Pacific Association of
      Gastroenterology consensus on tuberculosis infection in patients with
      inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part
      2: Management.
AB  - Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly
      popular in many Asian countries, the risk of developing active tuberculosis (TB)
      among anti-TNF users may raise serious health problems in this region. Thus, the
      Asian Organization for Crohn's and Colitis and the Asia Pacific Association of
      Gastroenterology have developed a set of consensus statements about risk
      assessment, detection and prevention of latent TB infection, and management of
      active TB infection in patients with inflammatory bowel disease (IBD) receiving
      anti-TNF treatment. Twenty-three consensus statements were initially drafted and
      then discussed by the committee members. The quality of evidence and the strength
      of recommendations were assessed by using the Grading of Recommendations
      Assessment, Development, and Evaluation methodology. Web-based consensus voting
      was performed by 211 IBD specialists from nine Asian countries concerning each
      statement. A consensus statement was accepted if at least 75% of the participants
      agreed. Part 2 of the statements comprised three parts: (3) management of latent
      TB in preparation for anti-TNF therapy, (4) monitoring during anti-TNF therapy,
      and (5) management of an active TB infection after anti-TNF therapy. These
      consensus statements will help clinicians optimize patient outcomes by reducing
      the morbidity and mortality related to TB infections in patients with IBD
      receiving anti-TNF treatment.

PMID- 29024104
TI  - The healthy donor effect impacts self-reported physical and mental health -
      results from the Danish Blood Donor Study (DBDS).
AB  - AIMS: This study aimed at quantifying the healthy donor effect by comparing self
      perceived mental and physical health between blood donors and non-donors.
      BACKGROUND: In theory, the selection process known as the healthy donor effect
      should result in better self-perceived, health-related quality of life in donors
      than in non-donors. METHODS: The Short Form-12 data from the Danish Twin Registry
      (DTR) was compared with the data from the Danish Blood Donor Study (DBDS). Data
      on age, sex and smoking status were included in the analyses. The multivariable
      linear regression analysis was stratified by sex and age group intervals. Outcome
      variables were the mental component score (MCS) and the physical component score
      (PCS). RESULTS: A total of 28 982 and 36 913 participants from the DTR and the
      DBDS, respectively, were included in this study. Younger donors had higher MCS
      than non-donors, whereas MCS was only marginally high in older donors compared
      with non-donors. In contrast, PCS was almost similar for both young donors and
      non-donors. With the increase in age, non-donors had lower PCS than donors.
      CONCLUSIONS: Two selection patterns were revealed. Among young individuals,
      better self-perceived mental health was associated with a blood donor. With the
      increase in age, better self-perceived physical health was associated with blood
      donation.

PMID- 29024105
TI  - Highly Active and Readily Accessible Proline-Based Dizinc Catalyst for CO2
      /Epoxide Copolymerization.
AB  - In the pursuit of CO2 -based materials, the development of efficient catalysts
      for the alternating copolymerization of CO2 and epoxides to give polycarbonates
      is receiving particular attention. Desirable attributes for such catalysts are
      high copolymerization activity at low CO2 pressure, as well as chemo- and
      stereocontrol over the formed polymer. Here, we report a novel chiral zinc
      catalyst that can be isolated in 97 % yield from commercial sources, and that
      produces polycarbonates selectively from neat cyclohexene oxide under 1 bar of
      CO2 pressure at temperatures above 50  degrees C. At 80  degrees C reaction
      temperature, TONs of 1684 and initial TOFs up to 149 h-1 were measured, producing
      an isotactic-enriched polycarbonate with a probability Pm of 65 % for the
      formation of a meso diad. Insight into the dinuclear nature of the active species
      and the copolymerization progress has been gained from structural and
      spectroscopic studies.

PMID- 29024103
TI  - Functional interleukin-6 receptor-alpha is located in tanycytes at the base of
      the third ventricle.
AB  - Interleukin (IL)-6- /- mice develop mature onset obesity, whereas i.c.v.
      injection of IL-6 decreases obesity in rodents. Moreover, levels of IL-6 in
      cerebrospinal fluid (CSF) were reported to be inversely correlated with obesity
      in humans. Tanycytes lining the base of the third ventricle (3V) in the
      hypothalamus have recently been reported to be of importance for metabolism. In
      the present study, we investigated whether tanycytes could respond to IL-6 in the
      CSF. With immunohistochemistry using a well characterised antibody directed
      against the ligand binding receptor for IL-6, IL-6 receptor alpha (IL-6Ralpha),
      it was found that tanycytes, identified by the two markers, vimentin and dopamine
      and cAMP-regulated phosphoprotein of 32 kDa, contained IL-6Ralpha. There were
      fewer IL-6Ralpha on another type of ventricle-lining cells, ependymal cells, as
      identified by the marker glucose transporter-1. To demonstrate that the
      immunoreactive IL-6Ralpha were responsive to IL-6, we injected IL-6 i.c.v. This
      treatment increased immunoreactive phosphorylated signal transducer and activator
      of transcription-3 (pSTAT3) in tanycytes after 5 minutes and in cells in the
      medial part of the arcuate nucleus after 5 and 15 minutes.
      Intracerebroventricular injection of leptin exerted similar effects. As expected,
      i.p. injection of leptin also induced pSTAT3 staining in the hypothalamus,
      whereas i.p. IL-6 injection had little effect on this parameter.
      Intracerebroventricular or i.p. injection of vehicle only had no effect on pSTAT3
      immunoreactivity. In summary, there are functional IL-6Ralpha on tanycytes at the
      bottom of the 3V, in agreement with the possibility that ventricular
      administration of IL-6 decreases obesity in mice via an effect on this cell type.

PMID- 29024106
TI  - Nutritional evaluation of the legume Macrotyloma axillare using in vitro and in
      vivo bioassays in sheep.
AB  - This study consisted of two experiments with the following objectives: to
      evaluate the effects of tannins from the tropical legume macrotiloma (Macrotyloma
      axillare) on total gas and methane (CH4 ) production, as well as on ruminal
      fermentation parameters by performing an in vitro bioassay, with samples
      incubated with and without polyethylene glycol (PEG) in a semi-automatic system;
      and secondly in a 17 day in vivo experiment, to determine apparent total tract
      digestibility (ATTD) of dietary nutrients and ruminal fermentation parameters of
      12 intact 8- to 9-month-old Santa Ines (averaging 24.95 +/- 1.8 kg body weight)
      ewes fed tropical grass hay supplemented with macrotiloma hay. The ewes were
      divided into two treatment groups depending on their diet: chopped aruana grass
      hay (Panicum maximum cv. Aruana) (control-CON); and aruana grass hay supplemented
      with chopped macrotiloma hay (macrotiloma-MAC). The animals were kept for 5
      consecutive days in metabolic cages for the ATTD assay, and at the end of this
      period, samples of rumen fluid were collected from each ewe to determine
      ammoniacal nitrogen (NH3 -N) and short-chain fatty acid (SCFA) production, and
      protozoa count. For the in vitro assay, a decrease in total gas and CH4
      production was observed for samples incubated without PEG (p < .05). No
      differences were observed for the other parameters evaluated (p > .05). In the in
      vivo experiment, increased intake and ATTD of crude protein were observed for the
      animals fed MAC when compared to CON (p < .05). For rumen fermentation
      parameters, increased NH3 -N, total SCFA and isobutyrate concentrations, as well
      as reduced protozoa count were observed for MAC when compared to CON (p < .05).
      The results observed here indicated the potential of macrotiloma for use as a
      ruminant feed, and antimethanogenic potential of this plant was noted.

PMID- 29024107
TI  - Multispeed genome diploidization and diversification after an ancient
      allopolyploidization.
AB  - Hybridization and genome doubling (allopolyploidy) have led to evolutionary
      novelties as well as to the origin of new clades and species. Despite the
      importance of allopolyploidization, the dynamics of postpolyploid diploidization
      (PPD) at the genome level has been only sparsely studied. The Microlepidieae
      (MICR) is a crucifer tribe of 17 genera and c. 56 species endemic to Australia
      and New Zealand. Our phylogenetic and cytogenomic analyses revealed that MICR
      originated via an intertribal hybridization between ancestors of Crucihimalayeae
      (n = 8; maternal genome) and Smelowskieae (n = 7; paternal genome), both native
      to the Northern Hemisphere. The reconstructed ancestral allopolyploid genome (n =
      15) originated probably in northeastern Asia or western North America during the
      Late Miocene (c. 10.6-7 million years ago) and reached the Australian mainland
      via long-distance dispersal. In Australia, the allotetraploid genome diverged
      into at least three main subclades exhibiting different levels of PPD and
      diversity: 1.25-fold descending dysploidy (DD) of n = 15 -> n = 12
      (autopolyploidy -> 24) in perennial Arabidella (3 species), 1.5-fold DD of n = 15
      -> n = 10 in the perennial Pachycladon (11 spp.) and 2.1-3.75-fold DD of n = 15 
      > n = 7-4 in the largely annual crown-group genera (42 spp. in 15 genera). These
      results are among the first to demonstrate multispeed genome evolution in taxa
      descending from a common allopolyploid ancestor. It is suggested that clade
      specific PPD can operate at different rates and efficacies and can be tentatively
      linked to life histories and the extent of taxonomic diversity.

PMID- 29024108
TI  - Changes in hepatic glucose and lipid metabolism-related parameters in domestic
      pigeon (Columba livia) during incubation and chick rearing.
AB  - This study aimed to evaluate the hepatic glucose and lipid metabolism-related
      parameters of adult male and female White King pigeons (Columba livia) during
      incubation and chick rearing. At day 4 (I4), 10 (I10) and 17 (I17) of incubation
      and day 1 (R1), 7 (R7), 15 (R15) and 25 (R25) of chick rearing, livers were
      sampled from six pigeons for each sex. Glycogen and fat contents, activities of
      glycolytic enzymes (hexokinase, HK; 6-phosphofructokinase, 6-PFK), and genes
      expressions of key enzymes involved in glycolysis (pyruvate kinase, PK;
      glucokinase, GK), gluconeogenesis (phosphoenolpyruvate carboxykinase cytosolic,
      PCK1; fructose-1,6-bisphosphatase, FBP1; glucose-6-phosphatase, G6Pase), fatty
      acid synthesis (fatty acid synthase, FAS; acetyl-CoA carboxylase, ACC) and fatty
      acid beta-oxidation (carnitine palmitoyltransferase 1, CPT1; acyl-CoA 1, ACO)
      were measured. In male and female pigeon livers, glycogen content and HK activity
      dramatically increased after I17 and after R1, respectively; expressions of FBP1
      and G6Pase genes were maximized at R15; activity of 6-PFK and expressions of PK
      and CPT1 genes were highest at R7; fat content and expressions of FAS and ACC
      genes steeply increased from I10 to R1. In females, hepatic expressions of GK and
      PCK1 genes were greatest at R7 and I17, respectively; however, in males, both of
      them were maximized at R15. Hepatic expression of ACO gene was significantly
      enhanced at R1 compared to I17 and R7 in males, whereas it was notably up
      regulated at I17 and R7 in females. Furthermore, expressions of PCK1, GK, FAS and
      ACC genes were in significant relation to fat content in the livers of female
      pigeons, while fat content in male pigeons was highly correlated with expression
      of PCK1, ACC, CPT1 and ACO genes. In conclusion, regulations of glucose and lipid
      metabolic processes were enhanced in parent pigeon livers from terminal phases of
      incubation to mid phase of chick rearing with sexual effects.

PMID- 29024109
TI  - Long-term use of proton pump inhibitors, dose-response relationship and
      associated risk of ischemic stroke and myocardial infarction.
AB  - BACKGROUND: Use of proton pump inhibitors (PPIs) has been associated with
      cardiovascular disease amongst patients not on antiplatelet therapy. The
      associations of PPI use, duration and dose, with risk of first-time ischemic
      stroke and myocardial infarction (MI) are poorly understood. METHODS: All Danish
      individuals with no prior history of MI or stroke, who had an elective upper
      gastrointestinal endoscopy performed between 1997 and 2012, were identified from
      nationwide registries. We used multiple Poisson regression to test associations
      with current PPI use and its dose and used multiple cause-specific Cox regression
      and g-formula methods to analyze long-term use. RESULTS: Amongst 214 998
      individuals, during a median follow-up of 5.8 years, there were 7916 ischemic
      strokes and 5608 MIs. Current PPI exposure was associated with significantly
      higher rates of both ischemic stroke (Hazard ratio (HR) 1.13; 95% confidence
      interval (CI) 1.08-1.19) and MI (HR 1.31, CI 1.23-1.39) after adjusting for age,
      sex, comorbidities and concomitant medication. High-dose PPI was associated with
      increased rates of ischemic stroke (HR 1.31, CI 1.21-1.42) and MI (HR 1.43, CI
      1.30-1.57). Histamine H2 receptor antagonists (H2RAs) use was not significantly
      associated with ischemic stroke (HR 1.02, CI 0.84-1.24) or MI (HR 1.15, CI 0.92
      1.43). Long-term users of PPIs, compared with nonusers, had a 29% (CI 5%-59%)
      greater absolute risk of ischemic stroke and a 36% (CI 7%-73%) greater risk of MI
      within a 6-month period. CONCLUSION: Use of PPIs was associated with increased
      risks of first-time ischemic stroke and MI, particularly amongst long-term users
      and at high doses.

PMID- 29024110
TI  - Therapeutic-Gas-Responsive Hydrogel.
AB  - Nitric oxide (NO) is a crucial signaling molecule with various functions in
      physiological systems. Due to its potent biological effect, the preparation of
      responsive biomaterials upon NO having temporally transient properties is a
      challenging task. This study represents the first therapeutic-gas (i.e., NO)
      responsive hydrogel by incorporating a NO-cleavable crosslinker. The hydrogel is
      rapidly swollen in response to NO, and not to other gases. Furthermore, the NO
      responsive gel is converted to enzyme-responsive gels by cascade reactions from
      an enzyme to NO production for which the NO precursor is a substrate of the
      enzyme. The application of the hydrogel as a NO-responsive drug-delivery system
      is proved here by revealing effective protein drug release by NO infusion, and
      the hydrogel is also shown to be swollen by the NO secreted from the cultured
      cells. The NO-responsive hydrogel may prove useful in many applications, for
      example drug-delivery vehicles, inflammation modulators, and as a tissue
      scaffold.

PMID- 29024111
TI  - Comment on: "Human symptom responses to bioeffluents, short-chain carbonyl/acids
      and long-chain carbonyls in a simulated aircraft cabin environment" by Weisel et
      al., Indoor Air (2017).

PMID- 29024112
TI  - A modeling enterprise for chemistry of indoor environments (CIE).

PMID- 29024113
TI  - Stress-related cortisol responsivity modulates prospective memory.
AB  - It is known that there is inter-individual variation in behavioural and
      physiological stress reactions to the same stressor. The present study aimed to
      examine the impact of cortisol responsivity on performance in a complex real life
      like prospective memory (PM) paradigm by a re-analysis of data published
      previously, with a focus on the taxonomy of cognitive dimensions of PM. Twenty
      one male subjects were stressed with the Socially Evaluated Cold Pressor Test
      (SECPT) before the planning of intentions. Another group of 20 males underwent a
      control procedure. Salivary cortisol was measured to assess the intensity of the
      biological stress response. Additionally, participants rated the subjective
      experience of stress on a 5-point rating scale. Stressed participants were post
      hoc differentiated in high (n = 11) and low cortisol responders (n = 10).
      Cortisol niveau differed significantly between the two groups, whereas subjective
      stress ratings did not. PM performance of low cortisol responders was stable
      across time and the PM performance of controls declined. High cortisol responders
      showed a nominally weaker PM retrieval across the early trails and significantly
      improved only on the last trial. The data demonstrate for the first time that
      participants with a low cortisol responsivity may benefit from stress exposure
      before the planning phase of PM. PM performance of high cortisol responders shows
      a more inconsistent pattern, which may be interpreted in the sense of a recency
      effect in PM retrieval. Alternatively, high cortisol responses may have a
      deteriorating effect on PM retrieval, which disappeared on the last trials of the
      task as a result of the decrease of cortisol levels across time. Importantly, the
      data also demonstrate that the intensity of cortisol responses does not
      necessarily correspond to the intensity of the mental experience of stress.

PMID- 29024114
TI  - Iron deficiency among blood donors: experience from the Danish Blood Donor Study
      and from the Copenhagen ferritin monitoring scheme.
AB  - Blood components collected from blood donors are an invaluable part of modern-day
      medicine. A healthy blood donor population is therefore of paramount importance.
      The results from the Danish Blood Donor Study (DBDS) indicate that gender, number
      of previous donations, time since last donation and menopausal status are the
      strongest predictors of iron deficiency. Only little information on the health
      effects of iron deficiency in blood donors exits. Possibly, after a standard full
      blood donation, a temporarily reduced physical performance for women is observed.
      However, iron deficiency among blood donors is not reflected in a reduced self
      perceived mental and physical health. In general, the high proportion of iron
      deficient donors can be alleviated either by extending the inter-donation
      intervals or by guided iron supplementation. The experience from Copenhagen, the
      Capital Region of Denmark, is that routine ferritin measurements and iron
      supplementation are feasible and effective ways of reducing the proportion of
      donors with low haemoglobin levels.

PMID- 29024115
TI  - Copper Photosensitizers Containing P^N Ligands and Their Influence on
      Photoactivity and Stability.
AB  - Driven by the intention to improve classic heteroleptic copper photosensitizers
      two novel Cu(I) complexes applying a hetero-bidentate P^N ligand were prepared. A
      combined photophysical, electrochemical, and theoretical study gives insights
      into structure-activity relationships and revealed an increased absorptivity.
      Both complexes were tested for the light-driven production of H2 .

PMID- 29024116
TI  - Different mutational function of low- and high-linear energy transfer heavy-ion
      irradiation demonstrated by whole-genome resequencing of Arabidopsis mutants.
AB  - Heavy-ion irradiation is a powerful mutagen that possesses high linear energy
      transfer (LET). Several studies have indicated that the value of LET affects DNA
      lesion formation in several ways, including the efficiency and the density of
      double-stranded break induction along the particle path. We assumed that the
      mutation type can be altered by selecting an appropriate LET value. Here, we
      quantitatively demonstrate differences in the mutation type induced by
      irradiation with two representative ions, Ar ions (LET: 290 keV MUm-1 ) and C
      ions (LET: 30.0 keV MUm-1 ), by whole-genome resequencing of the Arabidopsis
      mutants produced by these irradiations. Ar ions caused chromosomal rearrangements
      or large deletions (>=100 bp) more frequently than C ions, with 10.2 and 2.3 per
      mutant genome under Ar- and C-ion irradiation, respectively. Conversely, C ions
      induced more single-base substitutions and small indels (<100 bp) than Ar ions,
      with 28.1 and 56.9 per mutant genome under Ar- and C-ion irradiation,
      respectively. Moreover, the rearrangements induced by Ar-ion irradiation were
      more complex than those induced by C-ion irradiation, and tended to accompany
      single base substitutions or small indels located close by. In conjunction with
      the detection of causative genes through high-throughput sequencing, selective
      irradiation by beams with different effects will be a powerful tool for forward
      genetics as well as studies on chromosomal rearrangements.

PMID- 29024117
TI  - Molecularly imprinted polymers synthesized via template immobilization on fumed
      silica nanoparticles for the enrichment of phosphopeptides.
AB  - Phosphorylation is a protein post-translational modification (PTM) that plays an
      important role in cell signaling, cell differentiation, and metabolism. The hyper
      phosphorylated forms of certain proteins have been appointed as biomarkers for
      neurodegenerative diseases, and phosphorylation-related mutations are important
      for detecting cancer pathways. Due to the low abundance of phosphorylated
      proteins in biological fluids, sample enrichment is beneficial prior to
      detection. Thus, a need to find new strategies for enriching phosphopeptides has
      emerged. Molecularly imprinted polymers (MIPs) are synthetic polymeric materials
      manufactured to exhibit affinity for a target molecule. In this study, MIPs have
      been synthesized using a new approach based on the use of fumed silica as
      sacrificial support acting as solid porogen with the template (phosphotyrosine)
      immobilized on its surface. Phosphotyrosine MIPs were tested against a mixture of
      peptides and phosphopeptides by performing micro-solid phase extraction using
      MIPs (MUMISPE) packed in a pipette tip. First, the capability of the materials to
      preferentially enrich phosphopeptides was evaluated. In a next step, the
      enrichment of phosphopeptides from a whole-cell lysate of human embryonic kidney
      (HEK) 293T cells was performed. The eluates were analyzed using MALDI-MS in the
      first case and with nano-HPLC-ESI-MS/MS in the second case. The results showed
      that the MIPs provided affinity for phosphopeptides, binding preferentially to
      multi-site phosphorylated peptides. The MIPs could enrich phosphopeptides in over
      10-fold compared with the number of phosphopeptides found in a cell lysate
      without enrichment.

PMID- 29024118
TI  - Rice SUMO protease Overly Tolerant to Salt 1 targets the transcription factor,
      OsbZIP23 to promote drought tolerance in rice.
AB  - Conjugation of SUMO (Small Ubiquitin-like Modifier) protein to cellular targets
      is emerging as a very influential protein modification system. Once covalently
      bound, SUMO conjugation can change the stability or functionality of its cognate
      target proteins. SUMO protease can rapidly reverse SUMO conjugation making this
      modification system highly dynamic. A major factor in the variation of SUMO
      target function is the balance between the conjugated/de-conjugated forms. The
      mechanistic role of these regulatory SUMO proteases in mediating stress responses
      has not been defined in any crops. In this study, we reveal the role of the SUMO
      protease, OsOTS1 in mediating tolerance to drought in rice. OsOTS1 depleted
      transgenic plants accumulate more ABA and exhibit more productive agronomic
      traits during drought while OsOTS1 overexpressing lines are drought sensitive but
      ABA insensitive. Drought and ABA treatment stimulates the degradation of OsOTS1
      protein indicating that SUMO conjugation is an important response to drought
      stress in rice achieved through down-regulation of OTS1/2 activity. We reveal
      that OsOTS1 SUMO protease directly targets the ABA and drought responsive
      transcription factor OsbZIP23 for de-SUMOylation affecting its stability. OsOTS
      RNAi lines show increased abundance of OsbZIP23 and increased drought responsive
      gene expression while OsOTS1 overexpressing lines show reduced levels of OsbZIP23
      leading to suppressed drought responsive gene expression. Our data reveal a
      mechanism in which rice plants govern ABA-dependant drought responsive gene
      expression by controlling the stability of OsbZIP23 by SUMO conjugation through
      manipulating specific SUMO protease levels.

PMID- 29024120
TI  - Remodeling- and Modeling-Based Bone Formation With Teriparatide Versus Denosumab:
      A Longitudinal Analysis From Baseline to 3 Months in the AVA Study.
AB  - There has been renewed interest of late in the role of modeling-based formation
      (MBF) during osteoporosis therapy. Here we describe early effects of an
      established anabolic (teriparatide) versus antiresorptive (denosumab) agent on
      remodeling-based formation (RBF), MBF, and overflow MBF (oMBF) in human
      transiliac bone biopsies. Postmenopausal women with osteoporosis received
      subcutaneous teriparatide (n = 33, 20 MUg/d) or denosumab (n = 36, 60 mg once/6
      months), open-label for 6 months at 7 US and Canadian sites. Subjects received
      double fluorochrome labeling at baseline and before biopsy at 3 months. Sites of
      bone formation were designated as MBF if the underlying cement line was smooth,
      RBF if scalloped, and oMBF if formed over smooth cement lines adjacent to
      scalloped reversal lines. At baseline, mean RBF/bone surface (BS), MBF/BS, and
      oMBF/BS were similar between the teriparatide and denosumab groups in each bone
      envelope assessed (cancellous, endocortical, periosteal). All types of formation
      significantly increased from baseline in the cancellous and endocortical
      envelopes (differences p < 0.001) with teriparatide (range of changes 2.9- to
      21.9-fold), as did MBF in the periosteum (p < 0.001). In contrast, all types of
      formation were decreased or not significantly changed with denosumab, except
      MBF/BS in the cancellous envelope, which increased 2.5-fold (difference p =
      0.048). These data highlight mechanistic differences between these agents: all 3
      types of bone formation increased significantly with teriparatide, whereas
      formation was predominantly decreased or not significantly changed with
      denosumab, except for a slight increase in MBF/BS in the cancellous envelope. (c)
      2017 American Society for Bone and Mineral Research.

PMID- 29024121
TI  - The need to exercise caution in accepting addiction as a reason for performing
      euthanasia.
AB  - The recent practice in Belgium and the Netherlands of accepting addiction as a
      reason for performing euthanasia raises important issues for the field of
      addiction and the practice of euthanasia. In this paper we outline some of these
      issues. We also argue that physicians making decisions about whether to accept
      requests for euthanasia from people with an allegedly untreatable addiction
      should consider two issues carefully. They should ensure that: (1) the person has
      the capacity to give free and informed consent to undergo euthanasia; and (2)
      their request is the outcome of a deliberative process in which all reasonable
      treatment options and harm reduction measures have been offered to and considered
      by the person.

PMID- 29024119
TI  - Automatic segmentation of puborectalis muscle on three-dimensional transperineal
      ultrasound.
AB  - OBJECTIVES: The introduction of three-dimensional (3D) analysis of the
      puborectalis muscle (PRM) for diagnostic purposes into daily practice is hindered
      by the need for appropriate training of observers. Automatic segmentation of the
      PRM on 3D transperineal ultrasound may aid its integration into clinical
      practice. The aims of this study were to present and assess a protocol for manual
      3D segmentation of the PRM on 3D transperineal ultrasound, and to use this for
      training of automatic 3D segmentation method of the PRM. METHODS: The data used
      in this study were derived from 3D transperineal ultrasound sequences of the
      pelvic floor acquired at 12 weeks' gestation from nulliparous women with a
      singleton pregnancy. A manual 3D segmentation protocol was developed for the PRM
      based on a validated two-dimensional segmentation protocol. For automatic
      segmentation, active appearance models of the PRM were developed, trained using
      manual segmentation data from 50 women. The performances of both manual and
      automatic segmentation were analyzed by measuring the overlap and distance
      between the segmentations. Intraclass correlation coefficients (ICCs) and their
      95% CIs were determined for mean echogenicity and volume of the puborectalis
      muscle, in order to assess inter- and intraobserver reliabilities of the manual
      method using data from 20 women, as well as to compare the manual and automatic
      methods. RESULTS: Interobserver reliabilities for mean echogenicity and volume
      were very good for manual segmentation (ICCs 0.987 and 0.910, respectively), as
      were intraobserver reliabilities (ICCs 0.991 and 0.877, respectively). ICCs for
      mean echogenicity and volume were very good and good, respectively, for the
      comparison of manual vs automatic segmentation (0.968 and 0.626, respectively).
      The overlap and distance results for manual segmentation were as expected,
      showing an average mismatch of only 2-3 pixels and reasonable overlap. Based on
      overlap and distance, five mismatches were detected for automatic segmentation,
      resulting in an automatic segmentation success rate of 90%. CONCLUSIONS: This
      study presents a reliable manual segmentation protocol and automatic 3D
      segmentation method for the PRM, which will facilitate future investigation of
      the PRM, allowing for the reliable measurement of potentially clinically valuable
      parameters such as mean echogenicity. (c) 2017 The Authors. Ultrasound in
      Obstetrics & Gynecology Published by John Wiley & Sons Ltd on behalf of the
      International Society of Ultrasound in Obstetrics and Gynecology.

PMID- 29024122
TI  - Guided Molecular Assembly on a Locally Reactive 2D Material.
AB  - Atomically precise engineering of the position of molecular adsorbates on
      surfaces of 2D materials is key to their development in applications ranging from
      catalysis to single-molecule spintronics. Here, stable room-temperature
      templating of individual molecules with localized electronic states on the
      surface of a locally reactive 2D material, silicene grown on ZrB2 , is
      demonstrated. Using a combination of scanning tunneling microscopy and density
      functional theory, it is shown that the binding of iron phthalocyanine (FePc)
      molecules is mediated via the strong chemisorption of the central Fe atom to the
      sp3 -like dangling bond of Si atoms in the linear silicene domain boundaries.
      Since the planar Pc ligand couples to the Fe atom mostly through the in-plane d
      orbitals, localized electronic states resembling those of the free molecule can
      be resolved. Furthermore, rotation of the molecule is restrained because of
      charge rearrangement induced by the bonding. These results highlight how
      nanoscale changes can induce reactivity in 2D materials, which can provide unique
      surface interactions for enabling novel forms of guided molecular assembly.

PMID- 29024123
TI  - Morphological characterization of ckd in cats: Insights of fibrogenesis to be
      recognized.
AB  - Renal fibrosis is characterized by glomerulosclerosis and tubulointerstitial
      fibrosis and its pathogenesis is associated with the activity of mesenchymal
      cells (fibroblasts), being essentially characterized by a process of excessive
      accumulation resulting from the deposition of extracellular matrix components.
      The aim of this study was to characterize the morphological presentation of
      chronic and fibrotic lesions in the glomerular, tubular, interstitial, and
      vascular compartments in feline CKD, as well as the possible participation of
      myofibroblasts in renal fibrotic processes in this species. Cat kidneys were
      collected and processed according to the conventional techniques for light
      microscopy, circular polarization, immunohistochemistry, and electron microscopy.
      Fibrotic alterations were present in all compartments analyzed. The main findings
      in the glomerular compartment were different degrees of glomerular sclerosis,
      synechia formation, Bowman's capsule calcification, in addition to glomerular
      basement membrane thickening and pericapsular fibrosis. The tubulointerstitial
      compartment had intense tubular degeneration and the immunostaining in tubular
      cells for mesenchymal cell markers demonstrated the possibility of mesenchymal
      epithelial transition and consequent involvement of myofibroblasts in the
      development of interstitial tubule damage. Infiltration of inflammatory cells,
      added to vessel thickening and fibrosis, demonstrated the severity and role of
      inflammation in the development and perpetuation of damage. Thus, we may conclude
      that fibrotic lesions play a relevant role in feline CKD and the mechanism of
      perpetuation of these lesions need further elucidation regarding the origin and
      participation of myofibroblasts and consequent mesenchymal epithelial transition
      in this species.

PMID- 29024124
TI  - Examining a Dual-Process Model of Desensitization and Hypersensitization to
      Community Violence in African American Male Adolescents.
AB  - The purpose of the current study was to examine a dual-process model of
      reactivity to community violence exposure in African American male adolescents
      from urban communities. The model focused on desensitization and
      hypersensitization effects as well as desensitization and hypersensitization as
      predictors of aggressive behavior. Participants were 133 African American male
      high school students, mean age = 15.17 years, SD = 0.96. Participants completed
      measures of exposure to community violence, depressive symptoms, hyperarousal
      symptoms, aggressive beliefs, and aggressive behaviors at two time points.
      Community violence exposure predicted changes in aggression, beta = .25, p =
      .004, and physiological arousal, beta = .22, p = .010, over time, but not
      aggressive beliefs. The curvilinear association between community violence
      exposure and changes in depression over time was not significant, beta = .42, p =
      .083, but there was a significant linear association between the exposure to
      community violence (ECV) and changes in levels of depression over time, beta =
      .21, p = .014. Results indicated a significant mediation effect for hyperarousal
      on the association between community violence exposure and aggressive behavior, B
      = 0.20, 95% CI = [0.04, 0.54]. Results showed support for physiological
      hypersensitization, with hypersensitization increasing the risk for aggressive
      behavior.

PMID- 29024125
TI  - New Insights into the Operating Voltage of Aqueous Supercapacitors.
AB  - The main limitation of aqueous supercapacitors (SCs) lies in their narrow
      operating voltages, especially when compared with organic SCs. Fundamental
      understanding of factors relevant to the operating voltage helps providing
      guidance for the assembly of high-voltage aqueous SCs. In this regard, this
      concept analyzes the deciding factors for the operating voltage of aqueous SCs.
      Strategies applied to expand the operating voltage are summarized and discussed
      from the aspects of electrolyte, electrode, and asymmetric structure. Dynamic
      factors associated with water electrolysis and maximally using the available
      potential ranges of electrodes are particularly emphasized. Finally, other
      promising approaches that have not been explored and their challenges are also
      elaborated, hoping to provide more insights for the design of high-voltage
      aqueous SCs.

PMID- 29024126
TI  - Highly Crystalline C8-BTBT Thin-Film Transistors by Lateral Homo-Epitaxial Growth
      on Printed Templates.
AB  - Highly crystalline thin films of organic semiconductors offer great potential for
      fundamental material studies as well as for realizing high-performance, low-cost
      flexible electronics. The fabrication of these films directly on inert substrates
      is typically done by meniscus-guided coating techniques. The resulting layers
      show morphological defects that hinder charge transport and induce large device
      to-device variability. Here, a double-step method for organic semiconductor
      layers combining a solution-processed templating layer and a lateral homo
      epitaxial growth by a thermal evaporation step is reported. The epitaxial
      regrowth repairs most of the morphological defects inherent to meniscus-guided
      coatings. The resulting film is highly crystalline and features a mobility
      increased by a factor of three and a relative spread in device characteristics
      improved by almost half an order of magnitude. This method is easily adaptable to
      other coating techniques and offers a route toward the fabrication of high
      performance, large-area electronics based on highly crystalline thin films of
      organic semiconductors.

PMID- 29024127
TI  - Pacemapping guided by defibrillator electrograms for ventricular tachycardia
      ablation in a patient with ARVD/C.

PMID- 29024128
TI  - Foetal development of skeletal muscle in bovines as a function of maternal
      nutrition, foetal sex and gestational age.
AB  - To determine the effects of maternal nutrition on modifications of foetal
      development of the skeletal muscle and possible increase in the potential of
      skeletal muscle growth in cattle, gestating cows were either fed 190% NRC
      recommendations (overnourished; ON) or 100% NRC recommendation (control; CO).
      Interaction between maternal nutrition (MN) and the foetal sex (FS) was also
      investigated. Foetuses were necropsied at four different time points throughout
      gestation (139, 199, 241 and 268 days of gestation) to assess the mRNA expression
      of myogenic, adipogenic and fibrogenic markers in skeletal muscle. Phenotypic
      indicators of the development of skeletal muscle fibres, intramuscular
      lipogenesis and collagen development were also evaluated. Modifications in mRNA
      expression of skeletal muscle of foetuses were observed in function of MN and FS
      despite the lack of effect of MN and FS on foetal weight at necropsy. Maternal ON
      increased the mRNA expression of the myogenic marker Cadherin-associated protein,
      beta 1 (CTNNB1) and adipogenic markers Peroxissome proliferator-activated
      receptor gamma (PPARG) and Zinc finger protein 423 (ZNF423) at midgestation.
      However, no differences on foetal skeletal muscle development were observed
      between treatments at late gestation indicating that a compensatory development
      may have occurred on CO foetuses making the effect of MN on skeletal muscle
      development not significant at late gestation. Moreover, our data have shown an
      evidence of sexual dimorphism during foetal stage with a greater skeletal muscle
      development in male than in female foetuses. In conclusion, providing a higher
      nutritional level to pregnant cows changes the trajectory of the development of
      skeletal muscle during midgestation, but apparently does not change the potential
      of post-natal growth of muscle mass of the offspring, as no differences in
      skeletal muscle development were observed in late gestation.

PMID- 29024129
TI  - Efficacy of vitamins E and C for reversing the cytotoxic effects of nicotine and
      cotinine.
AB  - Nicotine has adverse cellular and molecular effects on oral mucosa, bone, and
      teeth. Vitamin E (alpha-tocopherol) and vitamin C (ascorbic acid) are biological
      antioxidants with positive effects on wound healing and bone formation. This in
      vitro study sought to assess the cytotoxic effects of different concentrations of
      nicotine and cotinine (a metabolite of nicotine) on MG-63 osteoblast-like cells
      and human gingival fibroblasts (HGFs) in the presence and absence of antioxidant
      vitamins E and C (separately and combined). Cell viability and proliferation were
      assessed using the methyl thiazol tetrazolium (MTT) assay. Cell migration was
      assessed using the scratch test, and expression of apoptosis-related genes was
      quantitatively analyzed using real-time PCR. Dose-dependent negative effects of
      nicotine on the morphology, viability, proliferation, and migration of MG-63 and
      HGF cells were statistically significantly greater than those of cotinine.
      Vitamin E (separately and combined with vitamin C) was statistically
      significantly more effective than vitamin C (at the concentration used in this
      study) at improving cell viability, proliferation, and migration, and at reducing
      apoptosis of cells exposed to nicotine or cotinine. Based on the positive results
      of this study, vitamin C and especially vitamin E (systemically and/or locally)
      may be useful in the repair and regeneration of oral hard and soft tissues in
      smokers.

PMID- 29024130
TI  - Continuity between DSM-5 Section II and Section III personality traits for
      obsessive-compulsive personality disorder.
AB  - OBJECTIVE: Obsessive-compulsive personality disorder (OCPD) is formally
      operationalized in Section II of the DSM-5 by a heterogeneous collection of 8
      categorical criteria. Section III contains an alternative model operationalizing
      personality disorders via dimensional personality traits and associated
      impairment. The extent to which the personality traits used to define OCPD in
      Section III correspond with the Section II operationalization of the disorder is
      contested. The current study aims to contribute to the evidence base necessary to
      solidify the optimal trait profile for this disorder via a more fine-tuned
      examination of OCPD. METHOD: The research questions were examined using a
      clinical sample of 142 Danish adults who completed the Structured Clinical
      Interview for DSM-IV Axis II Disorders and the Personality Inventory for DSM-5 to
      index both the Sections II and III (personality traits) operationalizations of
      OCPD, respectively. RESULTS: Bivariate correlations supported Rigid Perfectionism
      and Perseveration as traits relevant to OCPD; however, hierarchical regression
      analyses indicated that of the 4 traits used in the Section III
      operationalization of OCPD, only Rigid Perfectionism uniquely predicted OCPD (p <
      .05). In addition to Rigid Perfectionism, the conceptually relevant traits of
      Submissiveness, Suspiciousness, and (low) Impulsivity were also found to uniquely
      predict OCPD and its specific symptoms in a regression model. CONCLUSIONS: These
      findings indicate that the traits proposed in Section III are only partially
      aligned with the traditional, Section II conceptualization of OCPD, and may be
      augmented by incorporating Submissiveness, Suspiciousness, and (low) Impulsivity.
      In light of the current findings and existing literature, a modified
      constellation of traits to operationalize OCPD is likely justified.

PMID- 29024132
TI  - Expression of isotocin is male-specifically up-regulated by gonadal androgen in
      the medaka brain.
AB  - Oxytocin, a mammalian neuropeptide primarily synthesised in the supraoptic and
      paraventricular nuclei of the hypothalamus, mediates a variety of physiological
      and behavioural processes, ranging from parturition and lactation to affiliation
      and prosociality. Multiple studies in rodents have shown that the expression of
      the oxytocin gene (Oxt) is stimulated by oestrogen, whereas androgen has no
      apparent effect. However, this finding is not consistent across all studies, and
      no study has examined sex steroid regulation of Oxt or its orthologues in other
      animals. In the present study, we show that, in the teleost fish, medaka (Oryzias
      latipes), the expression of the isotocin gene (it), the teleost orthologue of
      Oxt, in the parvocellular preoptic nuclei (homologous to the mammalian supraoptic
      nucleus) is male-specifically up-regulated by gonadal androgen, whereas it
      expression in the magnocellular/gigantocellular preoptic nuclei (homologous to
      the mammalian paraventricular nucleus) is independent of sex steroids in both
      sexes. None of the it-expressing neurones appear to co-express androgen
      receptors, suggesting that the effect of androgen on it expression is indirect.
      We found that the expression of a kisspeptin gene, kiss2, in the male brain is
      dependent on gonadal androgen, raising the possibility that the androgen
      dependent expression of it may be mediated by kiss2 neurones. Our data also show
      that the isotocin peptide synthesised in response to androgen is axonally
      transported to the posterior pituitary to act peripherally. Given that levels of
      it expression are higher in females than in males, androgen may serve to
      compensate for the female-biased it expression to ensure a role for isotocin that
      is equally important for both sexes. These results are unexpectedly quite
      different from those reported in rodents, indicating that the regulatory role of
      sex steroids in Oxt/it expression has diverged during evolution, possibly with
      accompanying changes in the role of oxytocin/isotocin.

PMID- 29024131
TI  - The effect of dietary supplementation with Aurantiochytrium limacinum on
      lactating dairy cows in terms of animal health, productivity and milk
      composition.
AB  - The aim of this study was to investigate the effect of dietary supplementation
      with the docosahexaenoic acid (DHA)-rich microalgae, Aurantiochytrium limacinum
      (AURA), on a variety of health and productivity parameters in lactating cows.
      Twenty-four cows were blocked by parity and number of days in milk and then
      randomly assigned to a control (CON; n = 12) group with no algal supplementation,
      or a treatment group (AURA; n = 12) provided with 100 g AURA cow-1  day-1 or 16 g
      DHA cow-1  day-1 . A variety of health and productivity measurements were taken,
      and results indicated that supplementation had no negative effects on animal
      health in terms of somatic cell count, haematological and biochemical blood
      parameters, while body condition was marginally improved by algal
      supplementation. No differences were found for the various production parameters
      measured; however, a tendency towards increased milk production was observed for
      the AURA group during the final stage of the study (+4.5 kg cow-1  day-1 , day 78
      84). The fatty acid profile of milk was improved by supplementation, with
      significantly lower saturated fatty acids, significantly higher omega-3 fatty
      acids and an improved omega-3/omega-6 ratio observed when compared to the control
      group. The amount of DHA in the milk of cows provided 105 g AURA head-1  day-1
      was 4.7 mg/100 g milk with a peak transfer efficiency from feed to milk at day 49
      of 8.3%. These results indicate that supplementation with 105 g AURA head-1  day
      1 resulted in the successful enrichment of milk with DHA without negatively
      impacting the health or productivity of the animals.

PMID- 29024133
TI  - Plasma natriuretic peptide levels in fetuses with congenital heart defect and/or
      arrhythmia.
AB  - OBJECTIVE: Diagnosing fetal heart failure remains challenging because it is
      difficult to know how well the fetal myocardium will perform as loading
      conditions change. In adult cardiology, natriuretic peptides (NPs) are
      established markers of heart failure. However, the number of studies
      investigating NP levels in fetuses is quite limited. The aim of this study was to
      evaluate the significance of plasma NP levels in the assessment of heart failure
      in fetuses with a congenital heart defect (CHD) and/or arrhythmia. METHODS: This
      was a prospective observational study conducted at a tertiary pediatric cardiac
      center. A total of 129 singletons with CHD and/or arrhythmia and 127 controls
      were analyzed between 2012 and 2015. Umbilical cord plasma atrial NP, brain NP
      and N-terminal pro-brain NP levels at birth were compared with ultrasonography
      findings indicating fetal heart failure, such as cardiovascular profile (CVP)
      score and morphological characteristics. RESULTS: Fetuses with CHD and/or
      arrhythmia had higher NP levels than did controls (P < 0.01). NP levels of
      fetuses with CHD and/or arrhythmia were correlated inversely with CVP score (P
      for trend < 0.01). No differences in NP levels were found in fetuses with CHD
      and/or arrhythmia and a CVP score of >= 8 in comparison to controls. Multivariate
      analysis showed that a CVP score of <= 5, tachy- or bradyarrhythmia at birth,
      preterm birth and umbilical artery pH < 7.15 were associated independently with
      high NP levels (P < 0.01). Among fetuses with a CVP score of <= 7, abnormal
      venous Doppler sonography findings were significantly more common and more severe
      in fetuses with tachy- or bradyarrhythmia than in those with CHD, and those with
      tachy- or bradyarrhythmia had higher NP levels than did those with CHD (P =
      0.01). Fetuses with right-heart defect and moderate or severe tricuspid valve
      regurgitation had significantly higher NP levels than did fetuses with other
      types of CHD (P < 0.01). CONCLUSIONS: Plasma NP levels in fetuses with CHD and/or
      arrhythmia are correlated with the severity of fetal heart failure. Elevated NP
      levels are attributed mainly to an increase in central venous pressure secondary
      to arrhythmia or atrioventricular valve regurgitation due to CHD, rather than to
      the morphological abnormality itself. Copyright (c) 2017 ISUOG. Published by John
      Wiley & Sons Ltd.

PMID- 29024134
TI  - Telechelic Polybutadienes or Polyisoprenes Precursors for Recyclable Elastomeric
      Networks.
AB  - (Bis)furan-telechelic, low-molar-mass polybutadienes and polyisoprenes are
      synthesized by controlled degradation of high molar mass polymers and chain-end
      modifications yielding difunctional, trifunctional, or tetrafunctional polymers.
      Addition of a bismaleimide to the liquid-modified polymer leads to the formation
      of a thermoreversible elastomeric network based on the Diels-Alder chemistry for
      the trifunctional or tetrafunctional polymers, whereas only chain extension
      occurs for the bifunctional one. Dynamic mechanical analyses or tensile tests are
      performed on the networks and reveal a similar behavior for polyisoprene and
      polybutadiene with nevertheless quite different Young modulus or strain at break.
      The retro Diels-Alder reaction occurs upon heating, allowing the remolding of the
      used elastomer. The remolded network exhibits the same mechanical properties as
      the initial network, showing an efficient material recyclability.

PMID- 29024136
TI  - Streptavidin as a Scaffold for Light-Induced Long-Lived Charge Separation.
AB  - Long-lived photo-driven charge separation is demonstrated by assembling a triad
      on a protein scaffold. For this purpose, a biotinylated triarylamine was added to
      a RuII -streptavidin conjugate bearing a methyl viologen electron acceptor
      covalently linked to the N-terminus of streptavidin. To improve the rate and
      lifetime of the electron transfer, a negative patch consisting of up to three
      additional negatively charged amino acids was engineered through mutagenesis
      close to the biotin-binding pocket of streptavidin. Time-resolved laser
      spectroscopy revealed that the covalent attachment and the negative patch were
      beneficial for charge separation within the streptavidin hosted triad; the charge
      separated state was generated within the duration of the excitation laser pulse,
      and lifetimes up to 3120 ns could be achieved with the optimized supramolecular
      triad.

PMID- 29024135
TI  - Congenital Uterine Malformation by Experts (CUME): better criteria for
      distinguishing between normal/arcuate and septate uterus?
AB  - OBJECTIVES: To assess the level of agreement between experts in distinguishing
      between septate and normal/arcuate uterus using their subjective judgment when
      reviewing the coronal view of the uterus from three-dimensional ultrasound.
      Another aim was to determine the interobserver reliability and diagnostic test
      accuracy of three measurements suggested by recent guidelines, using as reference
      standard the decision made most often by experts (Congenital Uterine Malformation
      by Experts (CUME)). METHODS: Images of the coronal plane of the uterus from 100
      women with suspected fundal internal indentation were anonymized and provided to
      15 experts (five clinicians, five surgeons and five sonologists). They were
      instructed to indicate whether they believed the uterus to be normal/arcuate
      (defined as normal uterine morphology or not clinically relevant degree of
      distortion caused by internal indentation) or septate (clinically relevant degree
      of distortion caused by internal indentation). Two other observers independently
      measured indentation depth, indentation angle and indentation-to-wall-thickness
      (I:WT) ratio. The agreement between experts was assessed using kappa, the
      interobserver reliability was assessed using the concordance correlation
      coefficient (CCC), the diagnostic test accuracy was assessed using the area under
      the receiver-operating characteristics curve (AUC) and the best cut-off value was
      assessed using Youden's index, considering as the reference standard the choice
      made most often by the experts (CUME). RESULTS: There was good agreement between
      all experts (kappa, 0.62). There were 18 septate and 82 normal/arcuate uteri
      according to CUME; European Society of Human Reproduction and Embryology (ESHRE)
      European Society for Gynaecological Endoscopy (ESGE) criteria (I:WT ratio > 50%)
      defined 80 septate and 20 normal/arcuate uteri, while American Society for
      Reproductive Medicine (ASRM) criteria defined five septate (depth > 15 mm and
      angle < 90 degrees ), 82 normal/arcuate (depth < 10 mm and angle > 90 degrees )
      and 13 uteri that could not be classified (referred to as the gray-zone). The
      agreement between ESHRE-ESGE and CUME was 38% (kappa, 0.1); the agreement between
      ASRM criteria and CUME for septate was 87% (kappa, 0.39), and considering both
      septate and gray-zone as septate, the agreement was 98% (kappa, 0.93). Among the
      three measurements, the interobserver reproducibility of indentation depth (CCC,
      0.99; 95% CI, 0.98-0.99) was better than both indentation angle (CCC, 0.96; 95%
      CI, 0.94-0.97) and I:WT ratio (CCC, 0.92; 95% CI, 0.90-0.94). The diagnostic test
      accuracy of these three measurements using CUME as reference standard was very
      good, with AUC between 0.96 and 1.00. The best cut-off values for these
      measurements to define septate uterus were: indentation depth >= 10 mm,
      indentation angle < 140 degrees  and I:WT ratio > 110% . CONCLUSIONS: The
      suggested ESHRE-ESGE cut-off value overestimates the prevalence of septate uterus
      while that of ASRM underestimates this prevalence, leaving in the gray-zone most
      of the uteri that experts considered as septate. We recommend considering
      indentation depth >= 10 mm as septate, since the measurement is simple and
      reliable and this criterion is in agreement with expert opinion. Copyright (c)
      2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 29024137
TI  - Do male athletes with already high initial haemoglobin mass benefit from 'live
      high-train low' altitude training?
AB  - NEW FINDINGS: What is the central question of this study? It has been assumed
      that athletes embarking on an 'live high-train low' (LHTL) camp with already high
      initial haemoglobin mass (Hbmass ) have a limited ability to increase their
      Hbmass further post-intervention. Therefore, the relationship between initial
      Hbmass and post-intervention increase was tested with duplicate Hbmass measures
      and comparable hypoxic doses in male athletes. What is the main finding and its
      importance? There were trivial to moderate inverse relationships between initial
      Hbmass and percentage Hbmass increase in endurance and team-sport athletes after
      the LHTL camp, indicating that even athletes with higher initial Hbmass can
      reasonably expect Hbmass gains post-LHTL. It has been proposed that athletes with
      high initial values of haemoglobin mass (Hbmass ) will have a smaller Hbmass
      increase in response to 'live high-train low' (LHTL) altitude training. To verify
      this assumption, the relationship between initial absolute and relative Hbmass
      values and their respective Hbmass increase following LHTL in male endurance and
      team-sport athletes was investigated. Overall, 58 male athletes (35 well-trained
      endurance athletes and 23 elite male field hockey players) undertook an LHTL
      training camp with similar hypoxic doses (200-230 h). The Hbmass was measured in
      duplicate pre- and post-LHTL by the carbon monoxide rebreathing method. Although
      there was no relationship (r = 0.02, P = 0.91) between initial absolute Hbmass
      (in grams) and the percentage increase in absolute Hbmass , a moderate
      relationship (r = -0.31, P = 0.02) between initial relative Hbmass (in grams per
      kilogram) and the percentage increase in relative Hbmass was detected. Mean
      absolute and relative Hbmass increased to a similar extent (P >= 0.81) in
      endurance (from 916 +/- 88 to 951 +/- 96 g, +3.8%, P < 0.001 and from 13.1 +/-
      1.2 to 13.6 +/- 1.1 g kg-1 , +4.1%, P < 0.001, respectively) and team-sport
      athletes (from 920 +/- 120 to 957 +/- 127 g, +4.0%, P < 0.001 and from 11.9 +/-
      0.9 to 12.3 +/- 0.9 g kg-1 , +4.0%, P < 0.001, respectively) after LHTL. The
      direct comparison study using individual data of male endurance and team-sport
      athletes and strict methodological control (duplicate Hbmass measures and matched
      hypoxic dose) indicated that even athletes with higher initial Hbmass can
      reasonably expect Hbmass gain post-LHTL.

PMID- 29024138
TI  - Safranal Inhibits HeLa Cell Viability by Perturbing the Reassembly Potential of
      Microtubules.
AB  - Saffron, a spice from Crocus sativus, has been known for its health benefits and
      medicinal properties. Safranal is a component of saffron and is known for its
      antioxidant and anticancer properties. In this study, we elucidated a possible
      tubulin-targeted antiproliferative mechanism of action of safranal. In vitro, the
      compound perturbed secondary structure of tubulin without altering net
      microtubule polymer mass. It inhibited HeLa cell viability in a concentration
      dependent manner, with minimal damage to cellular microtubules. However, it
      strongly inhibited recovery of microtubule network after cold-induced
      disassembly, indicating its ability to interfere with the nucleation potential of
      tubulin. Further, as the acetylation pattern of the safranal-treated microtubules
      revealed, unlike many tubulin-targeted agents, the compound did not appear to
      induce persistent stabilization of microtubules. Our data shows an unusual,
      tubulin-targeted antiproliferative mechanism of safranal. Copyright (c) 2017 John
      Wiley & Sons, Ltd.

PMID- 29024139
TI  - Chlorpyrifos interacts with other agricultural stressors to alter stream
      communities in laboratory microcosms.
AB  - Chlorpyrifos is one of the most widely used agricultural insecticides in the
      world, but to date there is limited empirical information about its potential to
      interact with other common agricultural stressors. We conducted a 15-d, community
      level, microcosm experiment evaluating individual and combined effects of
      chlorpyrifos, nutrient enrichment, and sedimentation on stream invertebrate
      communities (abundance, biomass, richness, size structure, composition) and
      ecosystem processes (primary productivity and leaf decomposition). We found that
      sedimentation was the most detrimental stressor, with significant negative
      impacts on most invertebrate community and ecosystem function variables. Even
      though chlorpyrifos did not cause significant invertebrate mortality in the
      microcosms, it still altered ecosystem function by lowering leaf decomposition
      rates, probably through sublethal inhibition of invertebrate shredders.
      Furthermore, we observed a significant reversal interaction between chlorpyrifos
      and sediment for small-sized invertebrates collected in gravel (abundance in
      sediment * insecticide microcosms was 2.4 times lower than predicted by
      additivity), as well as an antagonistic interaction with nutrients on
      invertebrate richness in the same microhabitat (richness in nutrient *
      insecticide microcosms was 1.6 times higher than predicted by additivity). Our
      results suggest that chlorpyrifos has the potential to alter freshwater ecosystem
      function and interact non-additively with other common agricultural stressors.
      These findings are in keeping with a growing body of research highlighting that
      multiple stressor interactions and ecosystem processes should be considered when
      evaluating the impacts of organic toxicants on freshwater ecosystems.

PMID- 29024140
TI  - Do genetic drift and accumulation of deleterious mutations preclude adaptation?
      Empirical investigation using RADseq in a northern lacustrine fish.
AB  - Understanding genomic signatures of divergent selection underlying long-term
      adaptation in populations located in heterogeneous environments is a key goal in
      evolutionary biology. In this study, we investigated neutral, adaptive and
      deleterious genetic variation using 7,192 SNPs in 31 Lake Trout (Salvelinus
      namaycush) populations (n = 673) from Quebec, Canada. Average genetic diversity
      was low, weakly shared among lakes, and positively correlated with lake size,
      indicating a major role for genetic drift subsequent to lake isolation.
      Putatively deleterious mutations were on average at lower frequencies than the
      other SNPs, and their abundance relative to the entire polymorphism in each
      population was positively correlated with inbreeding, suggesting that the
      effectiveness of purifying selection was negatively correlated with inbreeding,
      as predicted from theory. Despite evidence for pronounced genetic drift and
      inbreeding, several outlier loci were associated with temperature and found in or
      close to genes with biologically relevant functions notably related to heat
      stress and immune responses. Outcomes of gene-temperature associations were
      influenced by the inclusion of the most inbred populations, in which allele
      frequencies deviated the most from model predictions. This result illustrates
      challenge in identifying gene-environment associations in cases of high genetic
      drift and restricted gene flow and suggests limited adaptation in populations
      experiencing higher inbreeding. We discuss the relevance of these findings for
      the conservation and management, notably regarding stocking and genetic rescue,
      of Lake Trout populations and other species inhabiting highly fragmented
      habitats.

PMID- 29024141
TI  - Rational Design and Synthesis of Unsaturated Se-Containing Osmacycles with sigma
      Aromaticity.
AB  - Isolation of the simplest 4pi three-membered heterocycles (1H-azirine, oxirene,
      thiirene, and selenirene) remains a big challenge due to their pi-antiaromaticity
      and significant ring strain. Here we demonstrate that the incorporation of a
      transition-metal fragment could stabilize the antiaromatic selenirene and
      pentalene frameworks simultaneously by density functional theory (DFT)
      calculations. Experimental verification leads to the Se-containing
      metallapolycycles, osmapentaloselenirenes, with remarkable thermal stability. The
      osmaselenirene unit in the metallapolycycle is determined to be the first example
      of sigma-aromaticity dominating in an unsaturated Se-containing ring. Our results
      not only highlight a remarkable stabilization by the transition-metal but also
      widen the scope of sigma-aromaticity in unsaturated rings, which is traditionally
      reserved for the domain of pi-aromaticity.

PMID- 29024142
TI  - Did Late Pleistocene climate change result in parallel genetic structure and
      demographic bottlenecks in sympatric Central African crocodiles, Mecistops and
      Osteolaemus?
AB  - The mid-Holocene has had profound demographic impacts on wildlife on the African
      continent, although there is little known about the impacts on species from
      Central Africa. Understanding the impacts of climate change on codistributed
      species can enhance our understanding of ecosystem dynamics and for formulating
      restoration objectives. We took a multigenome comparative approach to examine the
      phylogeographic structure of two poorly known Central African crocodile species
      Mecistops sp. aff. cataphractus and Osteolaemus tetraspis. In addition, we
      conducted coalescent-based demographic reconstructions to test the hypothesis
      that population decline was driven by climate change since the Last Glacial
      Maximum, vs. more recent anthropogenic pressures. Using a hierarchical Bayesian
      model to reconstruct demographic history, we show that both species had dramatic
      declines (>97%) in effective population size in the 'period following the Last
      Glacial Maximum 1,500-18,000 YBP. Identification of genetic structuring showed
      both species have similar regional structure corresponding to major geological
      features (i.e., hydrologic basin) and that small observed differences between
      them are best explained by the differences in their ecology and the likely impact
      that climate change had on their habitat needs. Our results support our
      hypothesis that climatic effects, presumably on forest and wetland habitat, had a
      congruent negative impact on both species.

PMID- 29024143
TI  - Fabrication of a Simple Acrylic Template to Standardize Periapical Radiographs
      for Implants Retaining Mandibular Bar Overdentures.
AB  - A standardized periapical radiograph is still the most suitable technique for
      monitoring peri-implant osseous destruction during long-term treatment. This
      article describes a new method for custom fabrication of an acrylic template with
      standardized reproducible assessment of implants retaining mandibular bar
      overdentures, without removal of the bar and regardless of the implant system
      used.

PMID- 29024146
TI  - Closing in on premature closure bias.

PMID- 29024147
TI  - Working with students with disabilities: simulation-based faculty development.

PMID- 29024149
TI  - Moving into relational empathy to address health disparities.

PMID- 29024150
TI  - Medical education research should extend further into clinical practice.

PMID- 29024151
TI  - Generic skills training through interprofessional peer-assisted learning.

PMID- 29024152
TI  - Teaching about ethics with an interprofessional mock trial.

PMID- 29024153
TI  - Developing measures for assessment of patient-centred communication: a case of
      the tail wagging the dog?

PMID- 29024154
TI  - Time required for a standard sunscreen to become effective following application:
      a UV photography study.

PMID- 29024155
TI  - Nanoparticle Regrowth Enhances Photoacoustic Signals of Semiconducting
      Macromolecular Probe for In Vivo Imaging.
AB  - Smart molecular probes that emit deep-tissue penetrating photoacoustic (PA)
      signals responsive to the target of interest are imperative to understand disease
      pathology and develop innovative therapeutics. This study reports a self-assembly
      approach to develop semiconducting macromolecular activatable probe for in vivo
      imaging of reactive oxygen species (ROS). This probe comprises a near-infrared
      absorbing phthalocyanine core and four poly(ethylene glycol) (PEG) arms linked by
      ROS-responsive self-immolative segments. Such an amphiphilic macromolecular
      structure allows it to undergo an ROS-specific cleavage process to release
      hydrophilic PEG and enhance the hydrophobicity of the nanosystem. Consequently,
      the residual phthalocyanine component self-assembles and regrows into large
      nanoparticles, leading to ROS-enhanced PA signals. The small size of the intact
      macromolecular probe is beneficial to penetrate into the tumor tissue of living
      mice, while the ROS-activated regrowth of nanoparticles prolongs the retention
      along with enhanced PA signals, permitting imaging of ROS during chemotherapy.
      This study thus capitalizes on stimuli-controlled self-assembly of macromolecules
      in conjunction with enhanced heat transfer in large nanoparticles for the
      development of smart molecular probes for PA imaging.

PMID- 29024156
TI  - Relationships between the second to fourth digit ratio (2D:4D) and game-related
      statistics in semi-professional female basketball players.
AB  - OBJECTIVE: Digit ratio (2D:4D) is a negative correlate of sports performance,
      although this relationship may be weak in open-skill sports such as basketball.
      The primary aim was to quantify relationships between 2D:4D and game-related
      statistics in semi-professional female basketball players. The secondary aim was
      to quantify the differences in mean 2D:4Ds between players based on their
      position in the starting lineup. METHODS: Using a cross-sectional design, 64
      female basketball players who competed in the South Australian Premier League
      were measured in-season for height, mass, and 2D:4D, with game-related statistics
      collected end-season. Partial correlations (adjusted for age and body mass index)
      were used to quantify relationships between right and left 2D:4Ds and game
      related statistics. Unpaired t-tests were used to quantify differences in mean
      2D:4Ds between starting and reserve players. RESULTS: 2D:4D was a substantial
      negative correlate of blocks, rebounds, and field-goal percentage; meaning,
      females with lower 2D:4Ds were generally better defensively as they recorded more
      blocks and rebounds, and were more efficient scorers, irrespective of their age
      and body size. Mean 2D:4D differed by position in the starting lineup, as females
      with lower 2D:4Ds were more likely to be in the starting lineup. CONCLUSIONS:
      This study found evidence that 2D:4D was a correlate of performance in an open
      skill sport. Female players with lower digit ratios tended to perform better in
      several aspects of basketball, especially defensively, and were more likely to be
      starters, suggesting they are the best players on the team in their positions.
      These results probably reflect the organizational benefits of prenatal
      testosterone.

PMID- 29024157
TI  - Regulation of nonylphenol-induced reproductive toxicity in mouse spermatogonia
      cells by miR-361-3p.
AB  - Nonylphenol (NP) is an environmental chemical that affects apoptosis and male
      infertility. In our study, we found that a high concentration of NP could down
      regulate the expression of microRNA-361-3p (miR-361-3p) in the murine GC-1
      spermatogonia cell line and in vivo in murine spermatogonia. Additionally, one
      direct target of this miR, the 3' untranslated region of Killin (Klln) mRNA, was
      identified. Klln encodes a transcription factor that directly regulates the
      expression of Tp73 (transcriptionally active p73), whose encoded protein can up
      regulate the expression of Puma (p53 upregulated modulator of apoptosis). Thus,
      our investigation revealed that the expression of Klln, Tp73, and Puma increased
      upon NP-dependent down-regulation of miR-361-3p, which eventually leads to
      apoptosis of spermatogonia.

PMID- 29024158
TI  - Income-rich and wealth-poor? The impact of measures of socio-economic status in
      the analysis of the distribution of long-term care use among older people.
AB  - This article aims to investigate the impact of using 2 measures of socio-economic
      status on the analysis of how informal care and home care use are distributed
      among older people living in the community. Using data from the Survey of Health,
      Ageing and Retirement in Europe for 14 European countries, we estimate
      differences in corrected concentration indices for use of informal care and home
      care, using equivalised household net income and equivalised net worth (as a
      proxy for wealth). We also calculate horizontal inequity indices using both
      measures of socio-economic status and accounting for differences in need. The
      findings show that using wealth as a ranking variable results, as a rule, in a
      less pro-poor inequality of use for both informal and home care. Once differences
      in need are controlled for (horizontal inequity), wealth still results in a less
      pro-poor distribution for informal care, in comparison with income, whereas the
      opposite is observed for home care. Possible explanations for these differences
      and research and policy implications are discussed.

PMID- 29024159
TI  - Chemical Patterning of High-Mobility Semiconducting 2D Bi2 O2 Se Crystals for
      Integrated Optoelectronic Devices.
AB  - Patterning of high-mobility 2D semiconducting materials with unique layered
      structures and superb electronic properties offers great potential for batch
      fabrication and integration of next-generation electronic and optoelectronic
      devices. Here, a facile approach is used to achieve accurate patterning of 2D
      high-mobility semiconducting Bi2 O2 Se crystals using dilute H2 O2 and protonic
      mixture acid as efficient etchants. The 2D Bi2 O2 Se crystal after chemical
      etching maintains a high Hall mobility of over 200 cm2 V-1 s-1 at room
      temperature. Centimeter-scale well-ordered arrays of 2D Bi2 O2 Se with tailorable
      configurations are readily obtained. Furthermore, integrated photodetectors based
      on 2D Bi2 O2 Se arrays are fabricated, exhibiting excellent air stability and
      high photoresponsivity of ~2000 A W-1 at 532 nm. These results are one step
      towards the practical application of ultrathin 2D integrated digital and
      optoelectronic circuits.

PMID- 29024160
TI  - Oxyresveratrol, a Stilbene Compound from Morus alba L. Twig Extract Active
      Against Trichophyton rubrum.
AB  - Morus alba L. (mulberry) twig is known to have an inhibitory effect on pathogens
      in traditional Chinese medicine. In the present study, the dermophytic fungus,
      Trichophyton rubrum, was used to evaluate the inhibitory effect of total M. alba
      twig extract and extracts obtained using solvents with different polarities by
      the method of 96-well MTT colorimetry. The main active substance was isolated and
      identified by tracking its activity. In addition, the inhibitory effects of
      active extracts and a single active substance were investigated in combination
      with miconazole nitrate. Our data indicated that ethyl acetate extracts of
      mulberry twig (TEE) exhibited a desired inhibitory activity on T. rubrum with the
      minimum inhibitory concentration (MIC) of 1.000 mg/mL. With activity tracking,
      the main substance showing antimicrobial activity was oxyresveratrol (OXY), which
      was isolated from TEE. Its MIC for inhibiting the growth of T. rubrum was 0.500
      mg/mL. The combined use of miconazole nitrate and OXY showed a synergistic
      inhibitory effect, as shown by a significant decrease in the MIC of both
      components. Based on the OXY content in TEE, the contribution rate of OXY to the
      inhibitory effect of TEE on T. rubrum was 80.52%, so it was determined to be the
      main antimicrobial substance in M. alba twig. Copyright (c) 2017 John Wiley &
      Sons, Ltd.

PMID- 29024161
TI  - Site-directed fluorescence labeling of intrinsically disordered region of human
      transcription factor YY1: The inhibitory effect of zinc ions.
AB  - Site-specific labeling of proteins with fluorescent dyes allows the study of
      protein structure and function using a wide variety of fluorescent techniques.
      However, specific labeling is not trivial in the case of proteins containing
      multiple cysteine residues. An example of such a protein is transcription factor
      Yin Yang 1, which comprises eight cysteine residues in four C2H2 type zinc
      fingers in the C-terminal region. Kinetic measurements of the labeling process
      allowed us to develop preparative labeling of three cysteine residues differently
      introduced to the N-terminal, disordered fragment of the protein. The protocol
      developed in the present study allows to prepare the protein with high recovery
      yield and high selectivity of the labeling. This was confirmed using proteolytic
      digestion and spectroscopic approach. The labeling process was significantly
      affected by the presence of zinc ions and was dependent on the localization of
      the engineered cysteine residue. This is the first known example of the use of
      cysteine metal protection and labeling (CyMPL) technology for the labeling of
      protein regions with no stable secondary structures.

PMID- 29024162
TI  - Sexuality and individual support plans for people with intellectual disabilities.
AB  - BACKGROUND: Sexual rights and sexuality are important aspects of quality of life,
      also for people with intellectual disabilities (IDs). However, providing support
      in this area to people with ID poses some challenges. In this study, the content
      of individual support plan (ISP) documents was analysed to determine the extent
      to which sexuality and sexual rights are addressed in part of the ISP documents.
      METHOD: Content analysis was carried out on a sample of 187 ISP documents from
      seven different service provider organisations in the Netherlands. First, we
      conducted a lexical search using terms related to sexuality and sexual health.
      The retrieved segments were then analysed. RESULTS: A total of 159 ISP documents
      (85%) of 60 men and 99 women contained some reference to aspects of sexuality.
      However, these references were mostly descriptive and offered little guidance in
      terms of providing support. Moreover, these notations mostly described negative
      or problematic aspects of sexuality. References to sexual education, treatment,
      intervention programs or support strategies were rarely found in the ISP
      documents. CONCLUSIONS: Although sexuality is addressed in most ISP documents,
      there is little information available about the provision of professional support
      in this area that would give people the opportunity to exert sexual rights. As
      sexuality and exerting sexual rights are important for people with ID as well as
      for other people, it is recommended that issues surrounding proactive sex
      education, shared decision-making and the implementation of sexual healthcare
      plans are addressed in the ISP.

PMID- 29024163
TI  - Ultrasonographic measurement of caudal vena cava to aorta ratios for
      determination of volume depletion in normal beagle dogs.
AB  - A noninvasive method for quantifying hydration status would be helpful for
      clinical management and for research applications in dogs. This prospective,
      experimental, pilot study aimed to assess the feasibility of ultrasonographic
      measurement of the caudal vena cava to aorta ratio as a method for quantifying
      volume depletion in dogs. In 12 normal beagle dogs, furosemide was administered
      intravenously at a dose of 1 mg/kg, every 2 h, for 8 h, to induce consecutive
      volume depletion. Every 30 min after administration, ultrasonographic images of
      the caudal vena cava and aorta, and physical and biological parameters related to
      dehydration were acquired. On transverse and longitudinal planes of caudal vena
      cava and aorta images, the height and area of the caudal vena cava and aorta were
      measured to calculate the caudal vena cava/aorta ratios. All images were acquired
      by approaching from the right intercostal space with the dogs in left lateral
      recumbency. A negative correlation was present between the percentage of weight
      loss in dogs and all four investigated caudal vena cava/aorta ratios (transverse
      plane width of the caudal vena cava [TW]/aorta; transverse plane height of caudal
      vena cava [TH]/aorta; longitudinal plane area of the caudal vena cava [TA]/aorta;
      and longitudinal plane maximal height of the caudal vena cava [L]/aorta).
      Significant differences (P < 0.001) were seen between dogs with and without
      clinical signs of dehydration for all caudal vena cava/aorta ratios. Findings
      indicated that ultrasonographic caudal vena cava/aorta ratios are feasible
      methods for quantifying volume depletion and for use as an adjunct to standard
      subjective methods for estimating hydration status in dogs.

PMID- 29024166
TI  - Aza versus Oxophilicity of SmI2 : A Break of a Paradigm.
AB  - Ligands that coordinate to SmI2 through oxygen are prevalent in the literature
      and make up a significant portion of additives employed with the reagent to
      perform reactions of great synthetic importance. In the present work a series of
      spectroscopic, calorimetric and kinetic studies demonstrate that nitrogen-based
      analogues of many common additives have a significantly higher affinity for Sm
      than the oxygen-based counterparts. In addition, electrochemical experiments show
      that nitrogen-based ligands significantly enhance the reducing power of SmI2 .
      Overall, this work demonstrates that the use of nitrogen-based ligands provides a
      useful alternative approach to enhance the reactivity of reductants based on SmII
      .

PMID- 29024165
TI  - Clinical yield of magnetoencephalography distributed source imaging in epilepsy:
      A comparison with equivalent current dipole method.
AB  - OBJECTIVE: Source localization of interictal epileptic discharges (IEDs) is
      clinically useful in the presurgical workup of epilepsy patients. It is usually
      obtained by equivalent current dipole (ECD) which localizes a point source and is
      the only inverse solution approved by clinical guidelines. In contrast, magnetic
      source imaging using distributed methods (dMSI) provides maps of the location and
      the extent of the generators, but its yield has not been clinically validated. We
      systematically compared ECD versus dMSI performed using coherent Maximum Entropy
      on the Mean (cMEM), a method sensitive to the spatial extent of the generators.
      METHODS: 340 source localizations of IEDs derived from 49 focal epilepsy patients
      with foci well-defined through intracranial EEG, MRI lesions, and surgery were
      analyzed. The comparison was based on the assessment of the sublobar concordance
      with the focus and of the distance between the source and the focus. RESULTS:
      dMSI sublobar concordance was significantly higher than ECD (81% vs 69%, P <
      0.001), especially for extratemporal lobe sources (dMSI = 84%; ECD = 67%, P <
      0.001) and for seizure free patients (dMSI = 83%; ECD = 70%, P < 0.001). The
      median distance from the focus was 4.88 mm for ECD and 3.44 mm for dMSI (P <
      0.001). ECD dipoles were often wrongly localized in deep brain regions.
      CONCLUSIONS: dMSI using cMEM exhibited better accuracy. dMSI also offered the
      advantage of recovering more realistic maps of the generator, which could be
      exploited for neuronavigation aimed at targeting invasive EEG and surgical
      resection. Therefore, dMSI may be preferred to ECD in clinical practice. Hum
      Brain Mapp 39:218-231, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29024168
TI  - Electronic-Reconstruction-Enhanced Tunneling Conductance at Terrace Edges of
      Ultrathin Oxide Films.
AB  - Quantum mechanical tunneling of electrons across ultrathin insulating oxide
      barriers has been studied extensively for decades due to its great potential in
      electronic-device applications. In the few-nanometers-thick epitaxial oxide
      films, atomic-scale structural imperfections, such as the ubiquitously existed
      one-unit-cell-high terrace edges, can dramatically affect the tunneling
      probability and device performance. However, the underlying physics has not been
      investigated adequately. Here, taking ultrathin BaTiO3 films as a model system,
      an intrinsic tunneling-conductance enhancement is reported near the terrace
      edges. Scanning-probe-microscopy results demonstrate the existence of highly
      conductive regions (tens of nanometers wide) near the terrace edges. First
      principles calculations suggest that the terrace-edge geometry can trigger an
      electronic reconstruction, which reduces the effective tunneling barrier width
      locally. Furthermore, such tunneling-conductance enhancement can be discovered in
      other transition metal oxides and controlled by surface-termination engineering.
      The controllable electronic reconstruction can facilitate the implementation of
      oxide electronic devices and discovery of exotic low-dimensional quantum phases.

PMID- 29024167
TI  - Imaging spinal cord atrophy in progressive myelopathies: HTLV-I-associated
      neurological disease (HAM/TSP) and multiple sclerosis (MS).
AB  - OBJECTIVE: Previous work measures spinal cord thinning in chronic progressive
      myelopathies, including human T-lymphotropic virus 1 (HTLV-1)-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP) and multiple sclerosis (MS).
      Quantitative measurements of spinal cord atrophy are important in fully
      characterizing these and other spinal cord diseases. We aimed to investigate
      patterns of spinal cord atrophy and correlations with clinical markers. METHODS:
      Spinal cord cross-sectional area was measured in individuals (24 healthy controls
      [HCs], 17 asymptomatic carriers of HTLV-1 (AC), 47 HAM/TSP, 74 relapsing
      remitting MS [RRMS], 17 secondary progressive MS [SPMS], and 40 primary
      progressive MS [PPMS]) from C1 to T10. Clinical disability scores, viral markers,
      and immunological parameters were obtained for patients and correlated with
      representative spinal cord cross-sectional area regions at the C2 to C3, C4 to
      C5, and T4 to T9 levels. In 2 HAM/TSP patients, spinal cord cross-sectional area
      was measured over 3 years. RESULTS: All spinal cord regions are thinner in
      HAM/TSP (56 mm2 [standard deviation, 10], 59 [10], 23 [5]) than in HC (76 [7], 83
      [8], 38 [4]) and AC (71 [7], 78 [9], 36 [7]). SPMS (62 [9], 66 [9], 32 [6]) and
      PPMS (65 [11], 68 [10], 35 [7]) have thinner cervical cords than HC and RRMS (73
      [9], 77 [10], 37 [6]). Clinical disability scores (Expanded Disability Status
      Scale [p = 0.009] and Instituto de Pesquisas de Cananeia [p = 0.03]) and CD8+ T
      cell frequency (p = 0.04) correlate with T4 to T9 spinal cord cross-sectional
      area in HAM/TSP. Higher cerebrospinal fluid HTLV-1 proviral load (p = 0.01) was
      associated with thinner spinal cord cross-sectional area. Both HAM/TSP patients
      followed longitudinally showed thoracic thinning followed by cervical thinning.
      INTERPRETATION: Group average spinal cord cross-sectional area in HAM/TSP and
      progressive MS show spinal cord atrophy. We further hypothesize in HAM/TSP that
      is possible that neuroglial loss from a thoracic inflammatory process results in
      anterograde and retrograde degeneration of axons, leading to the temporal
      progression of thoracic to cervical atrophy described here. Ann Neurol
      2017;82:719-728.

PMID- 29024164
TI  - Understanding the role of steroids in typical and atypical brain development:
      Advantages of using a "brain in a dish" approach.
AB  - Steroids have an important role in growth, development, sexual differentiation
      and reproduction. All four classes of steroids, androgens, oestrogens,
      progestogens and glucocorticoids, have varying effects on the brain. Androgens
      and oestrogens are involved in the sexual differentiation of the brain, and also
      influence cognition. Progestogens such as progesterone and its metabolites have
      been shown to be involved in neuroprotection, although their protective effects
      are timing-dependent. Glucocorticoids are linked with stress and memory
      performance, also in a dose- and time-dependent manner. Importantly, dysfunction
      in steroid function has been implicated in the pathogenesis of disease. Moreover,
      regulating steroid-signalling has been suggested as potential therapeutic avenue
      for the treatment of a number of neurodevelopmental, psychiatric and
      neurodegenerative disorders. Therefore, clarifying the role of steroids in
      typical and atypical brain function is essential for understanding typical brain
      functions, as well as determining their potential use for pharmacological
      intervention in the atypical brain. However, the majority of studies have thus
      far have been conducted using animal models, with limited work using native human
      tissue or cells. Here, we review the effect of steroids in the typical and
      atypical brain, focusing on the cellular, molecular functions of these molecules
      determined from animal models, and the therapeutic potential as highlighted by
      human studies. We further discuss the promise of human-induced pluripotent stem
      cells, including advantages of using three-dimensional neuronal cultures
      (organoids) in high-throughput screens, in accelerating our understanding of the
      role of steroids in the typical brain, and also with respect to their therapeutic
      value in the understanding and treatment of the atypical brain.

PMID- 29024169
TI  - How are multifactorial beliefs about the role of genetics and behavior in cancer
      causation associated with cancer risk cognitions and emotions in the US
      population?
AB  - OBJECTIVE: People who believe that cancer has both genetic and behavioral risk
      factors have more accurate mental models of cancer causation and may be more
      likely to engage in cancer screening behaviors than people who do not hold such
      multifactorial causal beliefs. This research explored possible health cognitions
      and emotions that might produce such differences. METHODS: Using nationally
      representative cross-sectional data from the US Health Information National
      Trends Survey (N = 2719), we examined whether endorsing a multifactorial model of
      cancer causation was associated with perceptions of risk and other cancer-related
      cognitions and affect. Data were analyzed using linear regression with jackknife
      variance estimation and procedures to account for the complex survey design and
      weightings. RESULTS: Bivariate and multivariable analyses indicated that people
      who endorsed multifactorial beliefs about cancer had higher absolute risk
      perceptions, lower pessimism about cancer prevention, and higher worry about harm
      from environmental toxins that could be ingested or that emanate from consumer
      products (Ps < .05). Bivariate analyses indicated that multifactorial beliefs
      were also associated with higher feelings of risk, but multivariable analyses
      suggested that this effect was accounted for by the negative affect associated
      with reporting a family history of cancer. Multifactorial beliefs were not
      associated with believing that everything causes cancer or that there are too
      many cancer recommendations to follow (Ps > .05). CONCLUSION: Holding
      multifactorial causal beliefs about cancer are associated with a constellation of
      risk perceptions, health cognitions, and affect that may motivate cancer
      prevention and detection behavior.

PMID- 29024170
TI  - Steroids, stress and the gut microbiome-brain axis.
AB  - It is becoming well established that the gut microbiome has a profound impact on
      human health and disease. In this review, we explore how steroids can influence
      the gut microbiota and, in turn, how the gut microbiota can influence hormone
      levels. Within the context of the gut microbiome-brain axis, we discuss how
      perturbations in the gut microbiota can alter the stress axis and behaviour. In
      addition, human studies on the possible role of gut microbiota in depression and
      anxiety are examined. Finally, we present some of the challenges and important
      questions that need to be addressed by future research in this exciting new area
      at the intersection of steroids, stress, gut-brain axis and human health.

PMID- 29024171
TI  - Demonstration of a long narrow critical isthmus of ischemic ventricular
      tachycardia by pace mapping.

PMID- 29024172
TI  - Benzyl Mono-P-Fluorophosphonate and Benzyl Penta-P-Fluorophosphate Anions Are
      Physiologically Stable Phosphotyrosine Mimetics and Inhibitors of Protein
      Tyrosine Phosphatases.
AB  - alpha,alpha-Difluoro-benzyl phosphonates are currently the most popular class of
      phosphotyrosine mimetics. Structurally derived from the natural substrate
      phosphotyrosine, they constitute classical bioisosteres and have enabled the
      development of potent inhibitors of protein tyrosine phosphatases (PTP) and
      phosphotyrosine recognition sites such as SH2 domains. Being dianions bearing two
      negative charges, phosphonates, however, do not permeate membranes and thus are
      often inactive in cells and have not been a successful starting point toward
      therapeutics, yet. In this work, benzyl phosphonates were modified by replacing
      phosphorus-bound oxygen atoms with phosphorus-bound fluorine atoms. Surprisingly,
      mono-P-fluorophosphonates were fully stable under physiological conditions, thus
      enabling the investigation of their mode of action toward PTP. Three alternative
      scenarios were tested and mono-P-fluorophosphonates were identified as stable
      reversible PTP1B inhibitors, despite of the loss of one negative charge and the
      replacement of one oxygen atom as an H-bond donor by fluorine. In extending this
      replacement strategy, alpha,alpha-difluorobenzyl penta-P-fluorophosphates were
      synthesized and found to be novel phosphotyrosine mimetics with improved affinity
      to the phosphotyrosine binding site of PTP1B.

PMID- 29024174
TI  - Li2 NH-LiBH4 : a Complex Hydride with Near Ambient Hydrogen Adsorption and Fast
      Lithium Ion Conduction.
AB  - Complex hydrides have played important roles in energy storage area. Here a
      complex hydride made of Li2 NH and LiBH4 was synthesized, which has a structure
      tentatively indexed using an orthorhombic cell with a space group of Pna21 and
      lattice parameters of a=10.121, b=6.997, and c=11.457 A. The Li2 NH-LiBH4 sample
      (in a molar ratio of 1:1) shows excellent hydrogenation kinetics, starting to
      absorb H2 at 310 K, which is more than 100 K lower than that of pristine Li2 NH.
      Furthermore, the Li+ ion conductivity of the Li2 NH-LiBH4 sample is about 1.0*10
      5  S cm-1 at room temperature, and is higher than that of either Li2 NH or LiBH4
      at 373 K. Those unique properties of the Li2 NH-LiBH4 complex render it a
      promising candidate for hydrogen storage and Li ion conduction.

PMID- 29024173
TI  - Root transcriptional dynamics induced by beneficial rhizobacteria and microbial
      immune elicitors reveal signatures of adaptation to mutualists.
AB  - Below ground, microbe-associated molecular patterns (MAMPs) of root-associated
      microbiota can trigger costly defenses at the expense of plant growth. However,
      beneficial rhizobacteria, such as Pseudomonas simiae WCS417, promote plant growth
      and induce systemic resistance without being warded off by local root immune
      responses. To investigate early root responses that facilitate WCS417 to exert
      its plant-beneficial functions, we performed time series RNA-Seq of Arabidopsis
      roots in response to live WCS417 and compared it with MAMPs flg22417 (from
      WCS417), flg22Pa (from pathogenic Pseudomonas aeruginosa) and fungal chitin. The
      MAMP transcriptional responses differed in timing, but displayed a large overlap
      in gene identity. MAMP-upregulated genes are enriched for genes with functions in
      immunity, while downregulated genes are enriched for genes related to growth and
      development. Although 74% of the transcriptional changes inflicted by live WCS417
      overlapped with the flg22417 profile, WCS417 actively suppressed more than half
      of the MAMP-triggered transcriptional responses, possibly to allow the
      establishment of a mutually beneficial interaction with the host root.
      Interestingly, the sector of the flg22417 -repressed transcriptional network that
      is not affected by WCS417 has a strong auxin signature. Using auxin response
      mutant tir1afb2afb3, we demonstrate a dual role for auxin signaling in finely
      balancing growth-promoting and defense-eliciting activities of beneficial
      microbes in plant roots.

PMID- 29024175
TI  - Mapping the sequence of brain events in response to disgusting food.
AB  - Warning signals indicating that a food is potentially dangerous may evoke a
      response that is not limited to the feeling of disgust. We investigated the
      sequence of brain events in response to visual representations of disgusting food
      using a dynamic image analysis. Functional MRI was acquired in 30 healthy
      subjects while they were watching a movie showing disgusting food scenes
      interspersed with the scenes of appetizing food. Imaging analysis included the
      identification of the global brain response and the generation of frame-by-frame
      activation maps at the temporal resolution of 2 s. Robust activations were
      identified in brain structures conventionally associated with the experience of
      disgust, but our analysis also captured a variety of other brain elements showing
      distinct temporal evolutions. The earliest events included transient changes in
      the orbitofrontal cortex and visual areas, followed by a more durable engagement
      of the periaqueductal gray, a pivotal element in the mediation of responses to
      threat. A subsequent core phase was characterized by the activation of
      subcortical and cortical structures directly concerned not only with the
      emotional dimension of disgust (e.g., amygdala-hippocampus, insula), but also
      with the regulation of food intake (e.g., hypothalamus). In a later phase, neural
      excitement extended to broad cortical areas, the thalamus and cerebellum, and
      finally to the default mode network that signaled the progressive termination of
      the evoked response. The response to disgusting food representations is not
      limited to the emotional domain of disgust, and may sequentially involve a
      variety of broadly distributed brain networks. Hum Brain Mapp 39:369-380, 2018.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 29024176
TI  - Family Instability and Exposure to Violence in the Early Life Course.
AB  - Family instability has been linked with a host of outcomes across the early life
      course. This study extends this literature by connecting instability with
      violence in the community by examining the associations among family structure,
      family structure change, and secondary exposure to violence during adolescence
      across diverse segments of the population. Using longitudinal data from the
      Project on Human Development in Chicago Neighborhoods study, we found that living
      with a single parent and experiencing family structure changes were associated
      with secondary exposure to violence. Multiple group models suggest that partner
      change translated into more exposure for boys than girls. Findings also suggest
      that family instability may lead to more secondary exposure to violence for
      African American youth.

PMID- 29024178
TI  - Familial clustering of oropharyngeal squamous cell carcinoma in the Utah
      population.
AB  - BACKGROUND: The main purpose of the current study was to define the familial
      aggregation of oropharyngeal squamous cell carcinoma (SCC) and risk to relatives
      of patients with oropharyngeal SCC. METHODS: We conducted a retrospective study
      utilizing linked population-based genealogy and state cancer registry databases
      between 1966 and 2012. Relative risks for oropharyngeal SCC and other
      malignancies among patients with oropharyngeal SCC and their relatives were
      estimated. RESULTS: Significant excess pairwise relatedness was observed for
      oropharyngeal SCC diagnosed before age 65 years. Significant excess risk for
      oropharyngeal SCC was observed for first-degree relatives of patients. Relatives
      of oropharyngeal SCC patients also demonstrated elevated rates of multiple other
      malignancies, including both lung and cervical cancers. CONCLUSION: Relatives of
      patients with oropharyngeal SCC display elevated risks of oropharyngeal, lung,
      and cervical cancers among others, suggesting a possible shared genetic etiology
      involving tobacco-related and human papillomavirus (HPV)-related malignancies.

PMID- 29024177
TI  - Differential regulation of two FLNA transcripts explains some of the phenotypic
      heterogeneity in the loss-of-function filaminopathies.
AB  - Loss-of-function mutations in the X-linked gene FLNA can lead to abnormal
      neuronal migration, vascular and cardiac defects, and congenital intestinal
      pseudo-obstruction (CIPO), the latter characterized by anomalous intestinal
      smooth muscle layering. Survival in male hemizygotes for such mutations is
      dependent on retention of residual FLNA function but it is unclear why a subgroup
      of males with mutations in the 5' end of the gene can present with CIPO alone.
      Here, we demonstrate evidence for the presence of two FLNA isoforms differing by
      28 residues at the N-terminus initiated at ATG+1 and ATG+82 . A male with CIPO
      (c.18_19del) exclusively expressed FLNA ATG+82 , implicating the longer protein
      isoform (ATG+1 ) in smooth muscle development. In contrast, mutations leading to
      reduction of both isoforms are associated with compound phenotypes affecting the
      brain, heart, and intestine. RNA-seq data revealed three distinct transcription
      start sites, two of which produce a protein isoform utilizing ATG+1 while the
      third utilizes ATG+82 . Transcripts sponsoring translational initiation at ATG+1
      predominate in intestinal smooth muscle, and are more abundant compared with the
      level measured in fibroblasts. Together these observations describe a new
      mechanism of tissue-specific regulation of FLNA that could reflect the differing
      mechanical requirements of these cell types during development.

PMID- 29024179
TI  - CaB2 S4 O16 : A Borosulfate Exhibiting a New Structure Type with Phyllosilicate
      Analogue Topology.
AB  - The reaction of Ca(CO3 ) with H3 BO3 in oleum (20 % SO3 ) yielded colorless
      single-crystals of CaB2 S4 O16 (monoclinic, P21 /c, a=5.5188(2), b=15.1288(6),
      c=13.2660(6) A, beta=92.88(1) degrees , V=1106.22(8) A3 ). X-ray single-crystal
      structure analysis revealed a phyllosilicate-analogue anionic sub-structure,
      forming 2D infinite anionic layers, which exhibit an unprecedented arrangement of
      condensed twelve-membered (zwolfer) and four-membered (vierer) rings of corner
      shared (SO4 ) and (BO4 ) tetrahedra. Charge compensation is achieved by Ca2+
      cations, residing exclusively above the centers of the twelve-membered rings. DFT
      investigations on the solid-state structure corroborate the experimental findings
      and allow for a detailed valuation of charge distribution within the anionic
      network and an assignment of vibrational frequencies.

PMID- 29024180
TI  - Modeling plant composition as community continua in a forest landscape with LiDAR
      and hyperspectral remote sensing.
AB  - In light of the need to operationalize the mapping of forest composition at
      landscape scales, this study uses multi-scale nested vegetation sampling in
      conjunction with LiDAR-hyperspectral remotely sensed data from the G-LiHT
      airborne sensor to map vascular plant compositional turnover in a compositionally
      and structurally complex North Carolina Piedmont forest. Reflecting a shift in
      emphasis from remotely sensing individual crowns to detecting aggregate optical
      structural properties of forest stands, predictive maps reflect the composition
      of entire vascular plant communities, inclusive of those species smaller than the
      resolution of the remotely sensed imagery, intertwined with proximate taxa, or
      otherwise obscured from optical sensors by dense upper canopies. Stand-scale
      vascular plant composition is modeled as community continua: where discrete
      community-unit classes at different compositional resolutions provide
      interpretable context for continuous gradient maps that depict n-dimensional
      compositional complexity as a single, consistent RGB color combination. In total,
      derived remotely sensed predictors explain 71%, 54%, and 48% of the variation in
      the first three components of vascular plant composition, respectively. Among all
      remotely sensed environmental gradients, topography derived from LiDAR ground
      returns, forest structure estimated from LiDAR all returns, and morphological
      biochemical traits determined from hyperspectral imagery each significantly
      correspond to the three primary axes of floristic composition in the study site.
      Results confirm the complementarity of LiDAR and hyperspectral sensors for
      modeling the environmental gradients constraining landscape turnover in vascular
      plant composition and hold promise for predictive mapping applications spanning
      local land management to global ecosystem modeling.

PMID- 29024181
TI  - Does the Risk Outweigh the Benefits? Adolescent Responses to Completing Health
      Surveys.
AB  - The aim of this study is to describe the self-reported experiences of adolescents
      in population-based samples when completing health-related surveys on topics with
      varying potential for evoking distress. Survey data were collected in three
      school-based studies of bullying behaviors (N = 1,771, 12-14 years), alcohol use
      (N = 823, 12, 15, and 17 years), and electronic image sharing (N = 274, 13
      years). Between 5% and 15% of respondents reported being upset at survey
      completion, but at most 1.4% were entirely negative in their evaluation. Age was
      not associated with being upset, but younger adolescents were more likely to see
      benefit in participation. Although concurrent mental health symptoms increased
      the risk of being upset, this was mostly mitigated by perceived benefits from
      participation.

PMID- 29024182
TI  - Large differences in proportions of harmful and benign amino acid substitutions
      between proteins and diseases.

PMID- 29024183
TI  - Seventh International AFMBioMed Conference on AFM in Life Sciences and Medicine,
      April 11 to 15, 2016, Porto, Portugal.

PMID- 29024184
TI  - The use of dipyrone (metamizol) as an analgesic in children: What is the
      evidence? A review.
AB  - Dipyrone has analgesic, spasmolytic, and antipyretic effects and is used to treat
      pain. Due to a possible risk of agranulocytosis with the use of dipyrone, it has
      been banned in a number of countries. The most commonly used data for the use of
      dipyrone are related to adults. Information relating to the use of dipyrone in
      children is scarce. Given the potential added value of dipyrone in the treatment
      of pain, a review of the literature was conducted to obtain more insight into the
      analgesic efficacy of dipyrone in children as well as the safety of dipyrone in
      terms of adverse events. A literature search was done for original articles (in
      English, German, or Spanish language) which met the following criteria: the use
      of dipyrone for pain and children up to the age of 17 years old. All titles and
      abstracts retrieved were reviewed, independently, by two of the authors, for
      their suitability for inclusion. The references of the selected articles were
      also checked for additional relevant papers. The publications were categorized
      into case reports, observational studies, or randomized controlled trials. To
      assess the methodological quality of the studies, the Jadad score was used. In
      the limited available data, the analgesic efficacy of intravenous dipyrone
      appears similar to that of intravenous paracetamol. Evidence is lacking to
      support the claim that dipyrone is equivalent or even superior to Non-Steroid
      Anti-Inflammatory-Drugs in pediatric pain. While the absolute risk of
      agranulocytosis with dipyrone in children, based on available literature, cannot
      be determined, case reports suggest that this risk is not negligible.

PMID- 29024185
TI  - Development of a tailored work-related support intervention for gastrointestinal
      cancer patients.
AB  - Aim is the development of a work-related support intervention, tailored to the
      severity of work-related problems of patients diagnosed with gastrointestinal
      (GI) cancer treated with curative intent. Two methods were used: (1) Work-related
      problems were identified from the literature and submitted to an expert panel
      during a modified Delphi study. Experts allocated work-related problems into
      degrees of severity: mild, severe or complex. In addition, experts indicated
      which health care professional should provide the tailored support: (2) These
      outcomes were combined with existing interventions to design the tailored
      intervention. Semi-structured interviews with experts were conducted to assess
      whether the intervention was comprehensive, and feasible for daily practice. A
      decision diagram measuring severity of work-related problems was developed based
      on the modified Delphi study with 44 experts, encompassing social, disease and
      occupational problems. Based on the degree of severity, support was provided by:
      an oncological nurse (mild), oncological occupational physician (severe) or
      multidisciplinary team (complex). The intervention encompassed three individual
      meetings in the clinical setting and was considered comprehensive and feasible by
      12 experts. The intervention is innovative in combining oncological and
      occupational care in the clinic and being tailored to the needs of GI cancer
      patients with specific work-related problems.

PMID- 29024186
TI  - Fear of cancer recurrence in oral and oropharyngeal cancer patients: An
      investigation of the clinical encounter.
AB  - Fear of cancer recurrence (FCR) is common among individuals treated for cancer.
      Explorations of how this fear is expressed within an oncology setting and
      responded to are currently lacking. The aim was to investigate how head and neck
      cancer survivors in follow-up consultations express FCR, investigate how a
      healthcare professional addresses recurrence fears, and examine how survivors
      experience this interaction. We recorded the follow-up consultations of those
      participants who have reported FCR as a concern on the Patient Concerns
      Inventory. We also conducted a follow-up phone interview with the participants.
      We analysed the transcripts using thematic analysis. Five men and six women were
      recruited, aged 55-87 (mean age = 64). Follow-up consultation analyses revealed
      that the consultant used "normalising FCR," "reassurance," and "offer of referral
      to a counsellor." Interviews revealed themes around how they coped with FCR,
      relevance of personal history on FCR, and the impact of feeling gratitude towards
      the consultant on expression of FCR. Analyses indicate that patients may feel
      reluctant to raise their FCR with their clinician for fear of appearing
      "ungrateful" or of damaging a relationship that is held in high esteem. Findings
      indicate the initiation of FCR with patients can be beneficial for patient
      support.

PMID- 29024187
TI  - Diversity of oxytocin neurons: beyond magno- and parvocellular cell types?
AB  - The hypothalamic neuropeptide oxytocin (OT), which is evolutionarily conserved
      among different species throughout the animal kingdom, is a key modulator of a
      variety of socio-emotional behaviors such as fear, trust and empathy. OT cells in
      the mammalian hypothalamus have been traditionally divided into two distinct
      types - magnocellular (magnOT) and parvocellular (parvOT) or preautonomic
      neurons. This distinction is based on OT cell sizes and shapes, projections,
      electrophysiological activity and functions. Indeed, while neuroendocrine magnOT
      neurons are known to primarily project their axons to the posterior pituitary and
      to a number of forebrain regions, non-neuroendocrine parvOT neurons have been
      seen as the main source of OT innervation of the brainstem and spinal cord to
      control autonomic functions and pain perception. However, very recent findings
      demonstrated distinct genetic profiles in OT neurons, allowing discrimination of
      at least four types of cells expressing OT. Furthermore, unexpected axonal
      projections of parvOT neurons to the forebrain and magnOT neurons to the midbrain
      have been newly reported. In this review, we focus on the detailed analysis of
      methods of distinction between OT cell types, in- and output sites, morphology as
      well as on the direct connectivity between OT neurons and its physiological
      significance. At the end, we propose a hypothesis that the central OT system is
      composed of more than just two OT cell types, which should be further verified by
      the application of available genetic and anatomical techniques. This article is
      protected by copyright. All rights reserved.

PMID- 29024188
TI  - The impact of sleep deprivation on visual perspective taking.
AB  - Total sleep deprivation (TSD) is known to alter cognitive processes. Surprisingly
      little attention has been paid to its impact on social cognition. Here, we
      investigated whether TSD alters levels-1 and -2 visual perspective-taking
      abilities, i.e. the capacity to infer (a) what can be seen and (b) how it is seen
      from another person's visual perspective, respectively. Participants completed
      levels-1 and -2 visual perspective-taking tasks after a night of sleep and after
      a night of TSD. In these tasks, participants had to take their own (self trials)
      or someone else's (other trials) visual perspective in trials where both
      perspectives were either the same (consistent trials) or different (inconsistent
      trials). An instruction preceding each trial indicated the perspective to take
      (i.e. the relevant perspective). Results show that TSD globally deteriorates
      social performance. In the level-1 task, TSD affects the selection of relevant
      over irrelevant perspectives. In the level-2 task, the effect of TSD cannot be
      unequivocally explained. This implies that visual perspective taking should be
      viewed as partially state-dependent, rather than a wholly static trait-like
      characteristic.

PMID- 29024189
TI  - Intron length polymorphism of beta-tubulin genes of Aegilops biuncialis Vis.
AB  - Intron-specific DNA polymorphism is present among plant beta-tubulin gene family
      members and is considered to be one of the molecular markers based on the
      difference of tubulin introns length assayed both separately (TBP: 1st intron) or
      in combination (h-TBP: 1st and 2nd introns). These two approaches are possibly
      useful for wheat breeding programs, since TBP and h-TBP help to differentiate
      between the accessions of Aegilops biuncialis Vis., a wild relative of wheat. PCR
      derived polymorphic fragments were resolved by PAGE electrophoresis. The length
      of amplicons varied significantly (395-3900 bp for TBP and 466-3440 bp for h
      TBP), while the numbers of polymorphic bands were 21 for TBP and 23 for h-TBP,
      respectively. PIC mean value was circa 0.3. Dendrograms constructed on the basis
      of the Nei and Li coefficient with the high bootstrap support reveal a similar
      order of hierarchy for the samples analyzed using both methods. Thus, both
      techniques uncover DNA polymorphism level sufficiently high to distinguish
      different accessions of Ae. biuncialis Vis.

PMID- 29024190
TI  - Naphthyl Thio- and Carba-xylopyranosides for Exploration of the Active Site of
      beta-1,4-Galactosyltransferase 7 (beta4GalT7).
AB  - Xyloside analogues with substitution of the endocyclic oxygen atom by sulfur or
      carbon were investigated as substrates for beta-1,4-galactosyltransferase 7
      (beta4GalT7), a key enzyme in the biosynthesis of glycosaminoglycan chains. The
      analogues with an endocyclic sulfur atom proved to be excellent substrates for
      beta4GalT7, and were galactosylated approximately fifteen times more efficiently
      than the corresponding xyloside. The 5a-carba-beta-xylopyranoside in the d
      configuration proved to be a good substrate for beta4GalT7, whereas the
      enantiomer in the l-configuration showed no activity. Further investigations by X
      ray crystallography, NMR spectroscopy, and molecular modeling provided a
      rationale for the pronounced activity of the sulfur analogues. Favorable pi-pi
      interactions between the 2-naphthyl moiety and a tyrosine side chain of the
      enzyme were observed for the thio analogues, which open up for the design of
      efficient GAG primers and inhibitors.

PMID- 29024191
TI  - Non-specific pleuritis in patients with active malignancy.
AB  - BACKGROUND AND OBJECTIVE: Pleuroscopy is the test of choice for patients with
      suspected malignant pleural effusion and negative cytology. Biopsies negative for
      malignancy are frequently attributed to non-specific pleuritis, which poses a
      dilemma in patients with a known active malignancy, raising concern for a false
      negative result. Our primary objective was to determine the outcomes of patients
      with active malignancy who had a non-malignant diagnosis on pleuroscopy. METHODS:
      Retrospective review of all pleuroscopy cases from January 2005 to January 2015
      at our institution was conducted. Biopsies were categorized by histopathology as
      malignant, eosinophilic or non-specific pleuritis. Malignant histopathology was
      considered a true positive. Eosinophilic or non-specific pleuritis was
      categorized as malignant, if malignancy was later identified during follow-up, or
      chemotherapy induced, possible radiation induced, other paramalignant, other
      benign or idiopathic. RESULTS: Of the 199 pleuroscopy cases reviewed, 172 (86%)
      had a history of active malignancy. On histopathology, 73 (42%) had malignancy, 9
      (5%) had eosinophilic pleuritis and 90 (52%) had non-specific pleuritis. Three
      patients with non-specific pleuritis were diagnosed with malignancy at follow-up.
      Pleuritis in 24 patients was chemotherapy induced, 27 were possibly radiation
      induced, 11 were other paramalignant and 3 were other benign. Idiopathic
      pleuritis was diagnosed in 31 patients. Patients were monitored for a mean of 23
      +/- 11 months. CONCLUSION: The prevalence of malignant pleural disease was lower
      than expected for our patient population. Patients with no malignancy on
      histopathology were most likely to have non-specific pleuritis, a cause for which
      was identified in a majority of patients after clinical review.

PMID- 29024192
TI  - Association of schizotypy with striatocortical functional connectivity and its
      asymmetry in healthy adults.
AB  - Altered striatocortical functional connectivity has been suggested to be a trait
      marker of schizophrenia spectrum disorders, including schizotypal personality. In
      the present study, we examined the association between schizotypal personality
      traits and striatocortical functional connectivity in a sample of healthy adults.
      The German version of the Schizotypal Personality Questionnaire was obtained from
      N = 111 participants recruited from the general public. Resting-state functional
      magnetic resonance imaging scans were acquired at 3T. Six striatal seed regions
      in each hemisphere were defined and striatocortical resting-state functional
      connectivity (rsFC) as well as its lateralization indices was calculated.
      Regression analysis showed that schizotypy scores, especially from the positive
      dimension, were positively correlated with rsFC between ventral striatum and
      frontal cortex and negatively associated with rsFC between dorsal striatum and
      posterior cingulate. No significant associations were found between negative
      dimension schizotypy and striatocortical rsFC. We also found positive
      correlations between schizotypy total scores and lateralization index of right
      dorsal caudate and right rostral putamen. In conclusion, the present study
      extends previous evidence of altered striatocortical rsFC in the schizophrenia
      spectrum. The observed associations resemble in part the alterations observed in
      psychotic patients and their relatives, providing support for dimensionality from
      schizotypal personality to the clinical disorder. Hum Brain Mapp 39:288-299,
      2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29024193
TI  - Interbrain phase synchronization during turn-taking verbal interaction-a
      hyperscanning study using simultaneous EEG/MEG.
AB  - Recently, neurophysiological findings about social interaction have been
      investigated widely, and hardware has been developed that can measure multiple
      subjects' brain activities simultaneously. These hyperscanning studies have
      enabled us to discover new and important evidences of interbrain interactions.
      Yet, very little is known about verbal interaction without any visual input.
      Therefore, we conducted a new hyperscanning study based on verbal, interbrain
      turn-taking interaction using simultaneous EEG/MEG, which measures rapidly
      changing brain activities. To establish turn-taking verbal interactions between a
      pair of subjects, we set up two EEG/MEG systems (19 and 146 channels of EEG and
      MEG, respectively) located ~100 miles apart. Subjects engaged in verbal
      communication via condenser microphones and magnetic-compatible earphones, and a
      network time protocol synchronized the two systems. Ten subjects participated in
      this experiment and performed verbal interaction and noninteraction tasks
      separately. We found significant oscillations in EEG alpha and MEG alpha/gamma
      bands in several brain regions for all subjects. Furthermore, we estimated phase
      synchronization between two brains using the weighted phase lag index and found
      statistically significant synchronization in EEG and MEG data. Our novel paradigm
      and neurophysiological findings may foster a basic understanding of the
      functional mechanisms involved in human social interactions. Hum Brain Mapp
      39:171-188, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29024194
TI  - Disrupted cortico-limbic connectivity during reward processing in remitted
      bipolar I disorder.
AB  - OBJECTIVES: Bipolar disorder (BD) is associated with elevated reward sensitivity
      and persistent positive affect, yet the neural mechanisms underlying these
      patterns are not well understood. In the present study, we examined putative
      disruptions in communication within a well-known cortico-limbic reward circuit
      during reward processing as a potential contributing mechanism to these symptoms.
      METHODS: The present investigation employed a within- and between-subjects design
      utilizing a monetary and social incentive delay task among adults with bipolar
      disorder type I (BD; N = 24) and a healthy non-psychiatric control group (HC; N =
      25) during functional magnetic resonance imaging (fMRI). Participants in the BD
      group were remitted at the time of testing. RESULTS: Functional connectivity
      analyses revealed increased connectivity between the ventral striatum (VS) seed
      region and orbitofrontal cortex (OFC) as well as the amygdala during processing
      of reward receipt in the BD group. After omission of expected rewards, the BD
      group showed decreased functional connectivity between the VS and a medial
      frontopolar cortex (mFPC) region associated with consideration of behavioral
      alternatives. Follow-up analyses within the BD group showed that increased VS-OFC
      connectivity after reward receipt, and decreased VS-mFPC connected after reward
      omission, were associated with higher levels of subthreshold mania symptoms.
      CONCLUSIONS: Results point toward potential mechanisms implicated in elevated
      reward sensitivity in BD. Enhanced VS-OFC connectivity after reward receipt may
      be involved in elevated valuation of rewards whereas blunted VS-mFPC connectivity
      after reward omission may reflect a failure to consider behavioral alternatives
      to reward pursuit.

PMID- 29024196
TI  - Pelvic floor muscle assessment on three- and four-dimensional transperineal
      ultrasound in women with ovarian endometriosis with or without retroperitoneal
      infiltration: a step towards complete functional assessment.
AB  - OBJECTIVES: Previous studies comparing women with deep infiltrating endometriosis
      (DIE) and healthy controls have underlined an association between pelvic floor
      muscle (PFM) hypertonic dysfunction and deep lesions. The aim of this study was
      to compare the morphometry of PFM in women affected by ovarian endometriosis with
      DIE vs those without DIE in order to assess the impact of retroperitoneal
      infiltration by the disease on PFM function. METHODS: This was a prospective
      study conducted between March 2015 and December 2016 on symptomatic women with a
      clinical and sonographic diagnosis of ovarian endometriosis with or without DIE,
      scheduled for laparoscopic surgery. We excluded patients with current or previous
      pregnancy, previous surgery for deep endometriosis, other causes of chronic
      pelvic pain or congenital or acquired abnormalities of pelvic floor anatomy.
      Three- and four-dimensional transperineal ultrasound was performed to evaluate
      PFM morphometry and assess levator hiatal area (LHA) and diameters at rest,
      during PFM contraction and during Valsalva maneuver. All volumes were analyzed
      offline by an investigator blinded to the clinical data. RESULTS: One hundred and
      fourteen patients with ovarian endometriosis were enrolled in the study, 75 with
      DIE and 39 without DIE. The diagnosis of endometriosis was confirmed by
      histological examination in all patients. Compared with women without DIE, women
      with DIE showed a smaller LHA at rest, during contraction and during Valsalva
      maneuver (P = 0.03, P = 0.03 and P = 0.02, respectively) and a smaller reduction
      in LHA during PFM contraction (P = 0.04). CONCLUSIONS: Women with ovarian
      endometriosis who were affected by DIE showed smaller hiatal dimensions than did
      women without DIE. Considering that PFM dysfunction in patients with DIE could
      cause pain symptoms and pelvic organ dysfunction, transperineal ultrasound could
      allow a more complete functional assessment and tailored therapy. Copyright (c)
      2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 29024198
TI  - Mucocele-like lesions diagnosed on breast core biopsy: Low risk of upgrade and
      subsequent carcinoma.
AB  - Mucocele-like lesions of the breast diagnosed on core biopsy are usually excised
      to exclude the possibility of partial sampling of an invasive mucinous carcinoma.
      The goal of this study was to correlate the pathologic and radiologic features of
      mucocele-like lesions to determine if excision is mandatory. Over a 16 year
      period we identified 32 patients with mucocele-like lesions diagnosed on 27 (84%)
      stereotactic and 5 (16%) ultrasound-guided core biopsies. The indications for
      core biopsy were: calcifications in 24 (75%), a mass in 7 (22%), and a mass with
      calcifications in 1 (3%). There were 22 (69%) mucocele-like lesions without
      atypia and 10 (31%) with atypical ductal hyperplasia or detached groups of
      atypical cells. Of the 22 mucocele-like lesions without atypia, 19 (86%) were
      excised: 15/19 (79%) were benign, 3/19 (16%) had atypical ductal hyperplasia and
      1/19 (5%) had ductal carcinoma in situ. None of the patients with mucocele-like
      lesions without atypia were upgraded to invasive carcinoma. The single patient
      who was upgraded to low-grade ductal carcinoma in situ had a history of ductal
      carcinoma in situ in the same breast. Of the 10 patients with mucocele-like
      lesions with atypia, 9 (90%) were excised: 5/9 (56%) were benign, 1/9 (11%) had
      atypical ductal hyperplasia and 3/9 (33%) had invasive carcinoma. Of the patients
      with mucocele-like lesions with atypia who were upgraded to invasive carcinoma,
      one had a BIRADS 5 mass and discordant pathology and one had a history of Hodgkin
      lymphoma and mantle radiation. There were 24 patients with mucocele-like lesions
      with or without atypia who were not upgraded on excision, and none developed
      breast cancer after a median of 51 months (range 7-192). These findings indicate
      that mucocele-like lesions without atypia are unlikely to be upgraded on excision
      and are associated with a low risk for the subsequent development of carcinoma.

PMID- 29024197
TI  - Multifaceted brain networks reconfiguration in disorders of consciousness
      uncovered by co-activation patterns.
AB  - INTRODUCTION: Given that recent research has shown that functional connectivity
      is not a static phenomenon, we aim to investigate the dynamic properties of the
      default mode network's (DMN) connectivity in patients with disorders of
      consciousness. METHODS: Resting-state fMRI volumes of a convenience sample of 17
      patients in unresponsive wakefulness syndrome (UWS) and controls were reduced to
      a spatiotemporal point process by selecting critical time points in the posterior
      cingulate cortex (PCC). Spatial clustering was performed on the extracted PCC
      time frames to obtain 8 different co-activation patterns (CAPs). We investigated
      spatial connectivity patterns positively and negatively correlated with PCC using
      both CAPs and standard stationary method. We calculated CAPs occurrences and the
      total number of frames. RESULTS: Compared to controls, patients showed (i)
      decreased within-network positive correlations and between-network negative
      correlations, (ii) emergence of "pathological" within-network negative
      correlations and between-network positive correlations (better defined with
      CAPs), and (iii) "pathological" increases in within-network positive correlations
      and between-network negative correlations (only detectable using CAPs). Patients
      showed decreased occurrence of DMN-like CAPs (1-2) compared to controls. No
      between-group differences were observed in the total number of frames CONCLUSION:
      CAPs reveal at a more fine-grained level the multifaceted spatial connectivity
      reconfiguration following the DMN disruption in UWS patients, which is more
      complex than previously thought and suggests alternative anatomical substrates
      for consciousness. BOLD fluctuations do not seem to differ between patients and
      controls, suggesting that BOLD response represents an intrinsic feature of the
      signal, and therefore that spatial configuration is more important for
      consciousness than BOLD activation itself. Hum Brain Mapp 39:89-103, 2018. (c)
      2017 Wiley Periodicals, Inc.

PMID- 29024195
TI  - Identification of zinc finger protein of the cerebellum 5 as a survival factor of
      prostate and colorectal cancer cells.
AB  - Identification of specific drug targets is very important for cancer therapy. We
      recently identified zinc finger protein of the cerebellum 5 (ZIC5) as a factor
      that promotes melanoma aggressiveness by platelet-derived growth factor D (PDGFD)
      expression. However, its roles in other cancer types remain largely unknown. Here
      we determined the roles of ZIC5 in prostate cancer (PCa) and colorectal cancer
      (CRC) cells. Results showed that ZIC5 was highly expressed in CRC and
      dedifferentiated PCa tissues, whereas little expression was observed in relevant
      normal tissues. Knockdown of ZIC5 decreased proliferation of several PCa and CRC
      cell lines with induction of cell death. ZIC5 knockdown significantly suppressed
      PDGFD expression transcriptionally, and PDGFD suppression also decreased
      proliferation of PCa and CRC cell lines. In addition, suppression of ZIC5 or
      PDGFD expression decreased levels of phosphorylated focal adhesion kinase (FAK)
      and signal transducer and activator of transcription 3 (STAT3) which are
      associated with PCa and CRC aggressiveness. Furthermore, knockdown of ZIC5 or
      PDGFD enhanced death of PCa and CRC cells induced by the anti-cancer drugs
      docetaxel or oxaliplatin, respectively. These results suggest that ZIC5 and PDGFD
      promote survival of PCa and CRC cells by enhancing FAK and STAT3 activity, and
      that the roles of ZIC5 are consistent across several cancer types.

PMID- 29024200
TI  - Novel automated point collection software facilitates rapid, high-density
      electroanatomical mapping with multiple catheter types.
AB  - INTRODUCTION: Manual, point-by-point electroanatomical mapping requires the
      operator to directly evaluate each point during map construction. Consequently,
      point collection can be a slow process. An automated 3D mapping system was
      developed with the goal of improving key mapping metrics, including map
      completion time and point density. METHODS: Automated 3D mapping software that
      includes morphology and cycle length discrimination functions for surface and
      intracardiac electrograms was developed. In five swine, electroanatomical maps
      (EAMs) of all four cardiac chambers were generated in sinus rhythm. Four
      catheters were used: two different four-pole ablation catheters, a 20-pole
      circular catheter, and a 64-pole basket catheter. Automated and manual 3D mapping
      were compared for 12 different catheter-chamber combinations (paired sets of 10
      maps for most combinations, for a total of 156 maps). RESULTS: Automated 3D
      mapping produced more than twofold increase in the number of points per map, as
      compared with manual 3D mapping (P <=0.007 for all catheter-chamber combinations
      tested). Automated 3D mapping also reduced map completion time by an average of
      29% (P < 0.05 for all comparisons). The amount of manual editing of the maps
      acquired with automated 3D mapping was minimal. CONCLUSION: Automated 3D mapping
      with the open-platform mapping software described in this study is significantly
      faster than manual, point-by-point 3D mapping. This resulted in shorter mapping
      time and higher point density. The morphology discrimination functions
      effectively excluded ectopic beats during mapping in sinus rhythm and allowed for
      rapid mapping of intermittent ventricular ectopic beats.

PMID- 29024199
TI  - Critical care pharmacy workforce: UK deployment and characteristics in 2015.
AB  - OBJECTIVE: Clinical pharmacists reduce medication errors and optimize the use of
      medication in critically ill patients, although actual staffing level and
      deployment of UK pharmacists is unknown. The primary aim was to investigate the
      UK deployment of the clinical pharmacy workforce in critical care and compare
      this with published standards. METHODS: An electronic data entry tool was created
      and distributed for UK critical care pharmacy services to record their critical
      care workforce deployment data. KEY FINDINGS: Data were received for 279 critical
      care units in 171 organizations. Clinical pharmacist input was identified for
      98.6% of critical care units. The median weekday pharmacist input to critical
      care was 0.045 whole time equivalents per Level 3 (ICU) bed with significant
      interregional variation. Weekend services were sparse. Pharmacists spent 24.5% of
      time on the multidisciplinary team ward round, 58.5% of time on independent
      patient review and 17% of time on other critical care professional support
      activities. There is significant variation in staffing levels when services are
      stratified by highest level of competence of critical care pharmacist within an
      organization (P = 0.03), with significant differences in time spent on the multi
      disciplinary ward round (P = 0.010) and on other critical care activities (P =
      0.009), but not on independent patient review. CONCLUSIONS: Investment in
      pharmacy services is required to improve access to clinical pharmacy expertise at
      weekends, on MDT ward rounds and for other critical care activities.

PMID- 29024201
TI  - Enantioseparation of racecadotril using polysaccharide-type chiral stationary
      phases in polar organic mode.
AB  - Enantioseparation of the antidiarrheal drug, racecadotril, was investigated by
      liquid chromatography using polysaccharide-type chiral stationary phases in polar
      organic mode. The enantiodiscrimininating properties of 4 different chiral
      columns (Chiralpak AD, Chiralcel OD, Chiralpak AS, Chiralcel OJ) with 5 different
      solvents (methanol, ethanol, 1-propanol, 2-propanol, and acetonitrile) at 5
      different temperatures (5-40  degrees C) were investigated. Apart from Chiralpak
      AS column the other 3 columns showed significant enantioseparation capabilities.
      Among the tested mobile phases, alcohol type solvents were superior over
      acetonitrile, and significant differences in enantioselective performance of the
      selector were observed depending on the type of alcohol employed. Van't Hoff
      analysis was used for calculation of thermodynamic parameters which revealed that
      enantioseparation is mainly enthalpy controlled; however, enthropic control was
      also observed. Enantiopure standard was used to determine the enantiomer elution
      order, revealing chiral selector-and mobile-phase dependent reversal of
      enantiomer elution order. Using the optimized method (Chiralcel OJ stationary
      phase, thermostated at 10  degrees C, 100% methanol, flow rate: 0.6 mL/min)
      baseline separation of racecadotril enantiomers (resolution = 3.00 +/- 0.02) was
      achieved, with the R-enantiomer eluting first. The method was validated according
      to the ICH guidelines, and its application was tested on capsule and granules
      containing the racemic mixture of the drug.

PMID- 29024202
TI  - Reluctance to fail nursing students in practice-implications for nurse managers.

PMID- 29024203
TI  - Megestrol acetate-caused adrenal insufficiency and delayed puberty in a male
      adolescent with spinal tumour.

PMID- 29024205
TI  - The Intact(r) breast lesion excision system as a therapeutic device for selected
      benign breast lesions.
AB  - The aim of this paper is to evaluate our Unit's initial experience using the
      Intact breast lesion excision system as a therapeutic excision option for benign
      or borderline breast lesions, which otherwise would entail open operative
      excision. The study includes the first 111 patients who underwent therapeutic
      excision with the intact radiofrequency system between December 2012 and May 2016
      performed at the Meirav Center for Breast Health, at the Chaim Sheba Medical
      Center, Ramat Gan Israel. The indications for the procedure included those
      patients who have benign, or atypical high risk lesions following a previous core
      needle biospy (CNB) who would have normally undergone conventional excision
      biopsy. After reviewing each case separately, we found that the use of the BLES
      system as a treatment device permitted the avoidance of operations that would
      have been otherwise indicated, in 98 cases of the total 111 in the cohort
      (88.3%). Thirteen cases eventually had to undergo surgical excision. In eight
      cases pathology was upgraded from the initial CNB to invasive or noninvasive
      carcinoma. Although the INTACT sysytem is most commonly used as an alternative
      biopsy technique for its diagnostic capabilities, this study assessed its
      clinical role as a definitive therapeutic excisional modality in selected cases
      of benign breast disease. It proved valuable in the majority of cases with
      avoidance of surgery where it was traditionally indicated, (98/111, 88.3%) and as
      definitive fibroadenoma management in a further 28 patients.

PMID- 29024206
TI  - The prevalence problem in the era of human papillomavirus screening.

PMID- 29024204
TI  - Establishment of a dog primary prostate cancer organoid using the urine cancer
      stem cells.
AB  - Dog spontaneously develop prostate cancer (PC) like humans. Because most dogs
      with PC have a poor prognosis, they could be used as a translational model for
      advanced PC in humans. Stem cell-derived 3-D organoid culture could recapitulate
      organ structures and physiology. Using patient tissues, a human PC organoid
      culture system was established. Recent study has shown that urine cells also
      possess the characteristic of stem cells. However, urine cell-derived PC
      organoids have never been produced. Therefore, we generated PC organoids using
      the dog urine samples. Urine organoids were successfully generated from each dog
      with PC. Each organoid showed cystic structures and resembled the epithelial
      structures of original tissues. Expression of an epithelial cell marker, E
      cadherin, and a myofibloblast marker, alpha-SMA, was observed in the urine
      organoids. The organoids also expressed a basal cell marker, CK5, and a luminal
      cell marker, CK8. CD49f-sorted basal cell organoids rapidly grew compared with
      CD24-sorted luminal cell organoids. The population of CD44-positive cells was the
      highest in both organoids and the original urine cells. Tumors were successfully
      formed with the injection of the organoids into immunodeficient mice. Treatment
      with a microtubule inhibitor, docetaxel, but not a cyclooxygenase inhibitor,
      piroxicam, and an mTOR inhibitor, rapamycin, decreased the cell viability of
      organoids. Treatment with a Hedgehog signal inhibitor, GANT61, increased the
      radiosensitivity in the organoids. These findings revealed that PC organoids
      using urine might become a useful tool for investigating the mechanisms of the
      pathogenesis and treatment of PC in dogs.

PMID- 29024207
TI  - Maternal vaccination as a Salmonella Typhimurium reduction strategy on pig farms.
AB  - AIMS: The control of Salmonella in pig production is necessary for public and
      animal health, and vaccination was evaluated as a strategy to decrease pig
      prevalence. METHODS AND RESULTS: The study examined the efficacy of a live
      Salmonella Typhimurium vaccine, administered to sows on eight commercial farrow
      to-finish herds experiencing clinical salmonellosis or Salmonella carriage
      associated with S. Typhimurium or its monophasic variants. Results of
      longitudinal Salmonella sampling were compared against eight similarly selected
      and studied control farms. At the last visit (~14 months after the start of
      vaccination), when all finishing stock had been born to vaccinated sows, both
      faecal shedding and environmental prevalence of Salmonella substantially declined
      on the majority of vaccinated farms in comparison to the controls. A higher
      proportion of vaccine farms resolved clinical salmonellosis than controls.
      However, Salmonella counts in positive faeces samples were similar between
      nonvaccinated and vaccinated herds. CONCLUSIONS: The results suggest that
      maternal vaccination is a suitable option for a Salmonella Typhimurium reduction
      strategy in farrow-to-finish pig herds. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Salmonella vaccines have the potential to reduce the prevalence of Salmonella in
      pigs and result in a reduction of human cases attributed to pork.

PMID- 29024209
TI  - Erratum.

PMID- 29024208
TI  - Does site of cord insertion increase risk of adverse outcome, twin-to-twin
      transfusion syndrome and discordant growth in monochorionic twin pregnancy?
AB  - OBJECTIVES: It is not currently well known to what extent the sites of cord
      insertion influence the risk of complicated outcome in monochorionic twin
      pregnancy. The objectives of this study were to examine whether the sites of cord
      insertion, as determined on prenatal ultrasound examination, affect the risks of
      adverse outcome, twin-to-twin transfusion syndrome (TTTS) and discordant growth,
      and whether discordance in insertion sites or velamentous insertion in one or
      both twins best predicts risk. METHODS: This was a retrospective cohort study of
      monochorionic diamniotic twin pregnancies followed from the first trimester. The
      cohort was divided into three groups of increasing discordance in cord insertion
      sites: concordant (normal-normal; marginal-marginal; velamentous-velamentous),
      intermediate (normal-marginal; marginal-velamentous) and discordant (normal
      velamentous). Adverse outcome was defined as fetal or neonatal loss or birth
      prior to 32 weeks. The associations of adverse outcome, TTTS and discordant
      growth were assessed using logistic regression analysis with the following
      predictors: the three groups of insertion sites and velamentous insertion in one
      or both twins. RESULTS: Included in the analysis were 518 pregnancies. On
      univariate analysis, both discordant and velamentous insertions in one twin
      increased the risk of adverse outcome, TTTS and discordant growth. Intermediate
      insertion only increased the risk of discordant growth. Velamentous insertion in
      both twins increased the risk of adverse outcome and TTTS, but not of discordant
      growth. Multivariate logistic regression analysis showed velamentous insertion in
      one or both twins to independently predict adverse outcome and TTTS. For
      discordant growth, both intermediate/discordant and velamentous cord insertion in
      one twin were independent predictors. CONCLUSIONS: Velamentous cord insertion in
      one or both twins increases the risk of adverse outcome and TTTS, irrespective of
      discordance in the insertion sites, whereas the risk of discordant growth is
      determined by both discordance in insertion sites and velamentous cord insertion
      in one twin. Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 29024210
TI  - A case of anaplastic lymphoma kinase-positive renal cell carcinoma coincident
      with Hodgkin lymphoma.
AB  - We report a case of ALK-positive renal cell carcinoma coincident with Hodgkin
      lymphoma. The patient was a 19 year-old-girl without sickle cell trait. The right
      renal tumor was discovered concomitantly with Hodgkin lymphoma (HL). After
      chemotherapy for HL, right nephrectomy was performed. Microscopically, the tumor
      showed a solid and focally pseudo-papillary growth pattern studded with tubular
      structures. Most tumor cells were small bland eosinophilic cells, but rhabdoid
      cells, vacuolated cells, pleomorphic multinucleated giant cells were also
      admixed. The variety of growth patterns and cell features led us to speculate a
      possibility of ALK-positive renal cell carcinoma (ALK + RCC). ALK was
      immunohistochemically positive, and fluorescence in situ hybridization analysis
      detected a split signal of the ALK gene. We examined previously reported partner
      genes (STRN, TPM3, VCL and EML4) by RT-PCR, but fusion gene was not detected. RCC
      showing solid or cribriform growth patterns with vacuolated cells with
      intracytoplamic lumina, rhabdoid cells, and mucus production indicates the
      possibility of ALK + RCC.

PMID- 29024211
TI  - The impact of holiday clubs on household food insecurity-A pilot study.
AB  - This research investigates whether holiday clubs have the potential to reduce
      food insecurity among households in the United Kingdom. We survey parents (n =
      38) of children attending seven different holiday clubs to estimate the
      percentage of children in those programmes who come from food insecure
      households. Results suggest that 42% (16 out of 38 respondents) of children come
      from households defined as "food insecure" and 24% (9 out of 38 respondents) come
      from households that are "food insecure with hunger." When secure and insecure
      households are compared, we discover that food insecure households benefit the
      most from holiday clubs, which suggests that they may play an important role in
      mitigating household food insecurity.

PMID- 29024212
TI  - Prevalence and predictive factors of left atrial tachycardia occurring after
      second-generation cryoballoon ablation of atrial fibrillation.
AB  - INTRODUCTION: Assess the prevalence and predictors of left atrial tachycardia
      (LAT) after cryoballoon ablation of pulmonary veins. METHODS AND RESULTS:
      Patients who underwent catheter ablation of pulmonary veins with a second
      generation cryoballoon for symptomatic paroxysmal (151 of 270, 56%) or persistent
      (119 of 270, 44%) atrial fibrillation were entered in a single-center prospective
      registry. Patients who experienced postcryoballoon LAT (pcryo-LAT) were selected
      on the basis of 12-lead ECG characteristics. Left atrial origin was confirmed
      during conventional EP study and electroanatomical activation mapping, and
      patients were treated by RF catheter ablation. Pcryo-LAT was observed in 15
      (5.6%) of 270 patients and was attributed to a reentrant mechanism in 11 patients
      (73%). The other four cases of pcryo-LAT were due to focal atrial tachycardia
      associated with reconnection of one pulmonary vein. In comparison with patients
      who remained in sinus rhythm, LA area (HR = 1.09; CI 1.01, 1.2; P = 0.02), LVEF
      (HR = 0.94; CI 0.90, 0.97; P < 0.001), and LVEF <50% (HR = 8.5; CI 3.1, 23.6; P <
      0.001) were predictors of pcryo-LAT. After multivariate Cox analysis, only left
      ventricular ejection fraction < 50% remained predictive of pcryo-LAT, (HR = 7.8,
      CI 2.3 26.7, P = 0.002). With a mean survival of 23 months, 73% of patients who
      experienced pcryo-LAT were in sinus rhythm versus 78% of patients without pcryo
      LAT (log rank P = 0.85). CONCLUSION: The prevalence of pcryo-LAT in patients with
      atrial fibrillation is low. Left ventricular ejection fraction < 50% is
      associated with an increased risk of pcryo-LAT. When treated by RF catheter
      ablation, the presence of pcryo-LAT is not a predictive factor of subsequent
      recurrence of atrial fibrillation during follow-up.

PMID- 29024213
TI  - The newborn rat gastric emptying rate is volume and not developmentally
      dependent.
AB  - BACKGROUND: Gastric residuals are a common finding in enterally fed preterm
      neonates and traditionally thought to reflect immaturity-related delayed gastric
      emptying. Adult human data suggest that the meal volume regulate the gastric
      emptying rate, but early in life, this has not been adequately evaluated. The
      goal of this study was to study the rat postnatal changes in gastric emptying
      rate and the strain-induced effect on muscle contraction. We hypothesized that
      the stomach content volume and not developmental factors determines the newborn
      gastric emptying rate, via the Rho-kinase 2 (ROCK-2) pathway. METHODS: Gastric
      volume and emptying rate measurements were obtained by ultrasound at different
      postprandial times and the wall strain-dependent changes in muscle contraction
      were evaluated ex vivo. KEY RESULTS: The newborn rat gastric emptying rate was
      unrelated to postnatal age, maximal 30 min postprandial, and directly
      proportional to content volume. In vitro measurements showed that the agonist
      induced gastric muscle contraction was directly proportional to the stomach wall
      strain. These changes were mediated via upregulation of ROCK-2 activity.
      CONCLUSIONS & INFERENCES: The newborn rat gastric emptying rate is not
      developmentally regulated, but dependent on the content volume via wall strain
      induced ROCK-2 activation. Further clinical studies addressing the content volume
      effect on the rate of gastric emptying are warranted, to enhance feeding
      tolerance in preterm neonates.

PMID- 29024215
TI  - Structural and functional features of lysine acetylation of plant and animal
      tubulins.
AB  - The study of the genome and the proteome of different species and representatives
      of distinct kingdoms, especially detection of proteome via wide-scaled analyses
      has various challenges and pitfalls. Attempts to combine all available
      information together and isolate some common features for determination of the
      pathway and their mechanism of action generally have a highly complicated nature.
      However, microtubule (MT) monomers are highly conserved protein structures, and
      microtubules are structurally conserved from Homo sapiens to Arabidopsis
      thaliana. The interaction of MT elements with microtubule-associated proteins and
      post-translational modifiers is fully dependent on protein interfaces, and almost
      all MT modifications are well described except acetylation. Crystallography and
      interactome data using different approaches were combined to identify conserved
      proteins important in acetylation of microtubules. Application of computational
      methods and comparative analysis of binding modes generated a robust predictive
      model of acetylation of the epsilon-amino group of Lys40 in alpha-tubulins. In
      turn, the model discarded some probable mechanisms of interaction between
      elements of interest. Reconstruction of unresolved protein structures was carried
      out with modeling by homology to the existing crystal structure (PDBID: 1Z2B)
      from B. taurus using Swiss-model server, followed by a molecular dynamics
      simulation. Docking of the human tubulin fragment with Lys40 into the active site
      of alpha-tubulin acetyltransferase, reproduces the binding mode of peptidomimetic
      from X-ray structure (PDBID: 4PK3).

PMID- 29024214
TI  - Regenerative medicine: Stroke survivor and carer views and motivations towards a
      proposed stem cell clinical trial using placebo neurosurgery.
AB  - BACKGROUND: Few studies explore stroke survivor views and motivations towards
      stem cell therapy (SCT). This qualitative study explores the views and
      motivations of both stroke survivors and their partners/carers towards a proposed
      2-arm Phase III Randomised Controlled Trial (RCT) comparing intracerebral
      insertion of stem cells with placebo neurosurgery in stroke survivors with
      disability. OBJECTIVE: To explore views and motivations towards a proposed 2-arm
      stem cell trial and identify factors that may impede and enhance participation.
      DESIGN: This study adopts a naturalistic design to explore the complexity of this
      field, employing a participatory action-research approach comprising a
      specialized Conversation (World) Cafe form of focus group. Data were collected
      via 5 Conversation Cafes with stroke survivors (age 40-75) and partners/carers
      between June and October 2016. Of 66 participants, 53 (31 male, 22 female) were
      stroke survivors and 13 (6 female, 7 male) were partners/carers. Qualitative data
      were analysed using a thematic approach. DISCUSSION AND CONCLUSION: Stroke
      survivor views and motivations reflect anticipation of the personal and future
      benefits of regenerative medicine. Partners/carers sought to balance the value of
      stroke survivor hope with carrying the weight of hope as carer, a conflict burden
      adding to known caregiver burden. All participants expressed the need for during
      and post-trial psychological support. This study provides a rare opportunity to
      explore the prospective views and motivations of stroke survivors and their
      partners/carers towards a proposed Phase III 2-arm RCT. This adds weight to
      qualitative evidence exploring capacity, consent, decision making, perceptions of
      treatment risk and supports required for clinical trial participation.

PMID- 29024216
TI  - Acrochordons on the neck; a remarkable clinical feature of tuberous sclerosis
      showing different patterns.

PMID- 29024217
TI  - Target of rapamycin FATC domain as a general membrane anchor: The FKBP-12 like
      domain of FKBP38 as a case study.
AB  - Increased efforts have been undertaken to better understand the formation of
      signaling complexes at cellular membranes. Since the preparation of proteins
      containing a transmembrane domain or a prenylation motif is generally challenging
      an alternative membrane anchoring unit that is easy to attach, water-soluble and
      binds to different membrane mimetics would find broad application. The 33-residue
      long FATC domain of yeast TOR1 (y1fatc) fulfills these criteria and binds to
      neutral and negatively charged micelles, bicelles, and liposomes. As a case
      study, we fused it to the FKBP506-binding region of the protein FKBP38 (FKBP38
      BD) and used 1 H-15 N NMR spectroscopy to characterize localization of the
      chimeric protein to micelles, bicelles, and liposomes. Based on these and
      published data for y1fatc, its use as a C-terminally attachable membrane anchor
      for other proteins is compatible with a wide range of buffer conditions (pH circa
      6-8.5, NaCl 0 to >150 mM, presence of reducing agents, different salts such as
      MgCl2 and CaCl2 ). The high water-solubility of y1fatc enables its use for
      titration experiments against a membrane-localized interaction partner of the
      fused target protein. Results from studies with peptides corresponding to the C
      terminal 17-11 residues of the 33-residue long domain by 1D 1 H NMR and CD
      spectroscopy indicate that they still can interact with membrane mimetics. Thus,
      they may be used as membrane anchors if the full y1fatc sequence is disturbing or
      if a chemically synthesized y1fatc peptide shall be attached by native chemical
      ligation, for example, unlabeled peptide to 15 N-labeled target protein for NMR
      studies.

PMID- 29024218
TI  - Using probability of drug use as independent variable in a register-based
      pharmacoepidemiological cause-effect study-An application of the reverse waiting
      time distribution.
AB  - BACKGROUND: In register-based pharmacoepidemiological studies, each day of follow
      up is usually categorized either as exposed or unexposed. However, there is an
      underlying continuous probability of exposure, and by insisting on a dichotomy,
      researchers unwillingly force a nondifferential misclassification into their
      analyses. We have recently developed a model whereby probability of exposure can
      be modeled, and we tested this on an empirical case of nonsteroidal anti
      inflammatory drug (NSAID)-induced upper gastrointestinal bleeding (UGIB).
      METHODS: We used a case-controls data set, consisting of 3568 cases of severe
      UGIB and 35 552 matched controls. Exposure to NSAID was based on 3 different
      conventional dichotomous measures. In addition, we tested 3 probabilistic
      exposure measures, a simple univariate backward-recurrence model, a "full"
      multivariable model, and a "reduced" multivariable model. Odds ratios (ORs) and
      95% confidence intervals for the association between NSAID use and UGIB were
      calculated by conditional logistic regression, while adjusting for preselected
      confounders. RESULTS: Compared to the conventional dichotomous exposure measures,
      the probabilistic exposure measures generated adjusted ORs in the upper range
      (4.37-4.75) while at the same time having the most narrow confidence intervals
      (ratio between upper and lower confidence limit, 1.46-1.50). Some ORs generated
      by conventional measures were higher than the probabilistic ORs, but only when
      the assumed period of intake was unrealistically short. CONCLUSION: The pattern
      of high ORs and narrow confidence intervals in probabilistic exposure measures is
      compatible with less nondifferential misclassification of exposure than in a
      dichotomous exposure model. Probabilistic exposure measures appear to be an
      attractive alternative to conventional exposure measures.

PMID- 29024219
TI  - The determinants of service complexity in children with intellectual
      disabilities.
AB  - BACKGROUND: To date, little is known about the predictors of healthcare service
      utilisation in children with intellectual disability (ID). The aim of this study
      was to identify the factors associated with service complexity in children with
      ID in Ontario, Canada. METHODS: The population of this cross-sectional study
      consisted of 330 children with ID ages 4 to 18 years who accessed mental health
      services from November of 2012 to June of 2016 in four agencies. All participants
      completed the interRAI Child and Youth Mental Health and Developmental Disability
      Assessment Instrument, which is a semi-structured clinician-rated assessment that
      covers a range of common issues in children with ID. The outcome of this study
      was a service complexity variable based on (1) mental health service utilisation
      including any services provided to the child and (2) the management involved in
      providing that care. Eight individual items were summed, resulting in a scale
      that ranged from 0 to 8. Scores were then dichotomised into two groups: a score
      of 0-2 identified children with a low service complexity and a score of 3 or
      higher identified children with a high service complexity. RESULTS: After
      adjustment for other covariates, gender was not associated with service
      complexity. Children aged 11-14 years and children with autism spectrum disorder
      used over twofold higher levels of service complexity than children aged equal to
      or less than 10 years or children with other causes of ID. Moreover, victims of
      bullying, high scores on the family functioning scale or learning or
      communication disorder were associated with greater service complexity.
      CONCLUSIONS: The findings of this study indicate that a variety of factors are
      related to service complexity ranged from children's nonclinical (age and
      experiences of bullying) to clinical (e.g. aggression, learning/communication
      problems and autism spectrum disorder) characteristics.

PMID- 29024221
TI  - Dendrites, deep learning, and sequences in the hippocampus.
AB  - The hippocampus places us both in time and space. It does so over remarkably
      large spans: milliseconds to years, and centimeters to kilometers. This works for
      sensory representations, for memory, and for behavioral context. How does it fit
      in such wide ranges of time and space scales, and keep order among the many
      dimensions of stimulus context? A key organizing principle for a wide sweep of
      scales and stimulus dimensions is that of order in time, or sequences. Sequences
      of neuronal activity are ubiquitous in sensory processing, in motor control, in
      planning actions, and in memory. Against this strong evidence for the phenomenon,
      there are currently more models than definite experiments about how the brain
      generates ordered activity. The flip side of sequence generation is
      discrimination. Discrimination of sequences has been extensively studied at the
      behavioral, systems, and modeling level, but again physiological mechanisms are
      fewer. It is against this backdrop that I discuss two recent developments in
      neural sequence computation, that at face value share little beyond the label
      "neural." These are dendritic sequence discrimination, and deep learning. One
      derives from channel physiology and molecular signaling, the other from applied
      neural network theory - apparently extreme ends of the spectrum of neural circuit
      detail. I suggest that each of these topics has deep lessons about the possible
      mechanisms, scales, and capabilities of hippocampal sequence computation.

PMID- 29024220
TI  - Differential expression of key subunits of SWI/SNF chromatin remodeling complexes
      in porcine embryos derived in vitro or in vivo.
AB  - In vitro embryo production is an established method for both humans and animals,
      but is fraught with inferior development and health issues in offspring born
      after in vitro fertilization procedures. Analysis of epigenetic changes caused by
      exposure to in vitro conditions should shed light on potential sources of these
      phenotypes. Using immunocytochemistry, we investigated the localization and
      relative abundance of components associated with the SWI/SNF (Switch/Sucrose non
      fermentable) chromatin-remodeling complex-including BAF155, BAF170, BAF180,
      BAF53A, BAF57, BAF60A, BAF45D, ARID1A, ARID1B, ARID2, SNF5, and BRD7-in oocytes
      and in in vitro-produced and in vivo-derived porcine embryos. Differences in the
      localization of BAF155, BAF170, BAF60A, and ARID1B among these sources indicate
      that improper timing of chromatin remodeling and cellular differentiation might
      occur in early preimplantation embryos produced and cultured in vitro.

PMID- 29024222
TI  - Recent Progress on the Confinement, Assembly, and Relaxation of Inorganic
      Functional Fillers in Polymer Matrix during Processing.
AB  - Functional polymer composites have gained extensive interest due to their wide
      range of applications. Various functionalities are mainly provided by functional
      fillers and their networks in polymer matrix. Therefore, morphology control on
      filler network has important influence on the final functionalities. The
      confinement, assembly, and relaxation of inorganic functional fillers in polymers
      are thought as the basic issues related to such control. Processing as the means
      to achieve the desired shape and properties for materials often involves strong
      temperature and shear field, among other factors-not to mention the complex
      interaction between polymer and filler. These processing fields and interactions
      during processing are reported to have profound influence on the confinement,
      assembly, and relaxation of inorganic fillers in polymer matrix. Therefore,
      various functionalities could be significantly affected by processing. This paper
      is a review of recent developments in this area.

PMID- 29024223
TI  - Hughes and Gleason's Virosaine A-Appreciating the Art in Synthesis.
AB  - The synthesis of the Securinega alkaloid virosaine A by Hughes and Gleason is a
      perfect example of the intersection of art and chemical synthesis. An ingenious
      cascade reaction builds most of the polycyclic architecture, but necessitates a
      challenging C-H functionalization, which is ultimately accomplished by an unusual
      directed lithiation reaction.

PMID- 29024224
TI  - Mass-Production of Mesoporous MnCo2 O4 Spinels with Manganese(IV)- and Cobalt(II)
      Rich Surfaces for Superior Bifunctional Oxygen Electrocatalysis.
AB  - A mesoporous MnCo2 O4 electrode material is made for bifunctional oxygen
      electrocatalysis. The MnCo2 O4 exhibits both Co3 O4 -like activity for oxygen
      evolution reaction (OER) and Mn2 O3 -like performance for oxygen reduction
      reaction (ORR). The potential difference between the ORR and OER of MnCo2 O4 is
      as low as 0.83 V. By XANES and XPS investigation, the notable activity results
      from the preferred MnIV - and CoII -rich surface. The electrode material can be
      obtained on large-scale with the precise chemical control of the components at
      relatively low temperature. The surface state engineering may open a new avenue
      to optimize the electrocatalysis performance of electrode materials. The
      prominent bifunctional activity shows that MnCo2 O4 could be used in metal-air
      batteries and/or other energy devices.

PMID- 29024225
TI  - Snail-mediated cancer stem cell-like phenotype in human CNE2 nasopharyngeal
      carcinoma cell.
AB  - BACKGROUND: Cancer stem cell (CSC)-like phenotype, which has been proven to play
      a critical role in invasion and metastasis of many kinds of cancers, has also
      been reported to be associated with epithelial-mesenchymal transition. Snail, a
      potent repressor of E-cadherin expression, was found to have a function to
      regulate the aforementioned processes. METHODS: In the current study, expression
      of putative CSCs biomarkers and the ratio of CSC-like CNE2 (cancer cell line) in
      total CNE2 were measured, and CSC-like characteristics were analyzed with tumor
      sphere self-renewal and colony-forming assays. Migration and invasion properties
      were determined by using transwell and wound healing assays. Xenograft tumor
      assays in vivo were done to evaluate the function of Snail and radiation in the
      tumor forming ability. RESULTS: In human nasopharyngeal carcinoma (NPC) cells,
      overexpression of Snail mediates a CSC-like phenotype, which enhances the
      initiation, invasion, and migration ability of cancer cells. CONCLUSION: Thus,
      Snail is a potential therapeutic target in NPC.

PMID- 29024226
TI  - Anger and depressive ruminations as predictors of dysregulated behaviours in
      borderline personality disorder.
AB  - BACKGROUND: Anger and depressive ruminations have recently received empirical
      attention as processes related to borderline personality disorder (BPD). The
      Emotional Cascade Model (Selby, Anestis, & Joiner, 2008) suggests that negative
      affect (such as anger and sadness) may trigger rumination, which in turn may
      increase the duration and extent of negative affect, leading to dysregulated
      behaviours aimed at reducing such intense and unpleasant emotions. AIM: The aim
      of this study is to explore the relationships between emotional dysregulation,
      anger and depressive ruminations, and their role in predicting dysregulated
      behaviours (such as aggression and self-harm) in a clinical sample of patients
      with BPD. METHODS: Ninety-one patients with a diagnosis of BPD were recruited
      from three outpatient community mental health centres and asked to complete a
      comprehensive assessment for personality disorder symptoms, emotion
      dysregulation, anger and depressive ruminations, aggression, and self-harm.
      RESULTS: Anger and depressive ruminations were found to be significantly
      associated to, respectively, self-harm and aggression, beyond the variance
      accounted by emotional dysregulation. CONCLUSIONS: Rumination may act as a
      mediator between emotional dysregulation and dysregulated behaviours in BPD.
      Future research should examine whether clinical techniques aimed at reducing
      rumination may be helpful in reducing dysregulated behaviours in patients with
      BPD.

PMID- 29024227
TI  - Impact of atrial fibrillation on rest and exercise haemodynamics in heart failure
      with mid-range and preserved ejection fraction.
AB  - AIMS: Heart failure with preserved (HFpEF) and mid-range ejection fraction
      (HFmrEF) are becoming the most prevalent forms of heart failure. Patients with
      HFpEF/HFmrEF in atrial fibrillation (AF) have poorer survival and quality of
      life, but the mechanism underpinning this is unknown. We sought to investigate
      the influence of AF on the haemodynamic profile of HFpEF/HFmrEF patients at rest
      and during exercise. METHODS AND RESULTS: We invasively measured central
      haemodynamics at rest and during symptom-limited supine bicycle exercise in
      HFpEF/HFmrEF patients, 35 in sinus rhythm and 20 in AF with matched left
      ventricular ejection fraction. At rest, AF patients had significantly increased
      pulmonary capillary wedge pressure, lower cardiac index and reduced left
      ventricular stroke work index, despite similar resting heart rate. Under resting
      conditions, calculated oxygen consumption and systemic arteriovenous oxygen
      gradient were not different between the two groups. During supine cycling at
      similar levels of workload, AF patients exhibited a reduced capacity to increase
      their oxygen consumption and this was accompanied by a persistently impaired
      cardiac index and left ventricular stroke work index. CONCLUSIONS: The adverse
      interaction of AF and HFpEF/HFmrEF may be accounted for by an adverse impact on
      left ventricular systolic function and peripheral oxygen kinetics.

PMID- 29024228
TI  - De novo hepatocellular carcinoma post-multivisceral transplantation in a child.
AB  - De novo hepatocellular carcinoma (HCC) post-transplantation in patients without
      viral hepatitis is extremely rare, with only three reported adult cases in the
      English literature. Here, we present a case of de novo HCC that developed in a 7
      year-old female, who at 8 months of age received a liver, small bowel, spleen,
      and pancreas transplantation 6.5 years ago for gastroschisis and total parenteral
      nutrition (TPN)-related cirrhosis. The post-transplant course was complicated by
      Epstein-Barr virus (EBV) infection, post-transplant lymphoproliferative disease,
      and subsequent development of multifocal EBV-associated post-transplant smooth
      muscle tumors (EBV-PTSMT) in the small bowel 1 year and 10 months after
      transplantation, respectively. This was managed by reducing immunosuppression
      with rituximab and EBV-specific cytotoxic T-cell therapy. She was noted to have a
      new lesion in her transplanted liver graft 6.5 years post-transplantation that
      was diagnosed as HCC. The HCC was resected, and the patient remained clinically
      stable for 7 months. At that time, recurrence of the HCC was discovered on MRI.
      She passed away 6 months after. To the best of our knowledge, this is the first
      reported occurrence of de novo HCC post-transplantation in the pediatric
      population that is unrelated to viral hepatitis in either recipient or donor.

PMID- 29024229
TI  - Bioinspired Dynamic Wetting on Multiple Fibers.
AB  - Natural fibers have versatile strategies for interacting with water media and
      better adapting to the local environment, and these strategies offer inspiration
      for the development of artificial functional fibers with diverse applications.
      Wetting on fibers is a dynamic liquid-moving process on/in fibrous systems with
      various patterns, and the process is normally driven by the structural gradient,
      chemical gradient, elasticity of a single fiber, or the synergistic effect of
      these factors in multiple fibers in an integrated system in which the spatial
      geometry of the fibers is involved. Compared with the directional liquid movement
      on a single fiber, wetting on multiple fibers in both the micro- and macroscales
      is particularly fascinating, with various performances, including directional
      liquid transport, controllable liquid transfer, efficient liquid encapsulation,
      and capillary-induced fibrous coalescence. Based on these properties, fibrous
      materials offer an alternative open system for liquid manipulation that is
      applicable to various functional liquid materials. Here, recent achievements in
      bioinspired dynamic wetting on multiple fibers are highlighted, and perspectives
      on future directions are presented.

PMID- 29024230
TI  - gamma-Aminobutyric acid (GABA) oral rinse reduces capsaicin-induced burning mouth
      pain sensation: An experimental quantitative sensory testing study in healthy
      subjects.
AB  - BACKGROUND: In burning mouth patients, analgesia after oral administration of
      clonazepam may result from modulation of peripheral gamma-aminobutyric acid
      (GABA) receptors. METHODS: The effect of oral administration of test solutions
      (water, 0.5 mol/L or 0.05 mol/L GABA, 1% lidocaine) was investigated for the
      amelioration of pain and sensitivity induced by application of capsaicin (1%, 2
      min) to the tongue of thirty healthy male and female subjects in this four
      session, randomized, placebo-controlled, double-blinded, cross-over study. Intra
      oral quantitative sensory testing was used to assess cold (CDT), warm (WDT) and
      mechanical (MDT) detection thresholds as well as mechanical (MPT) and heat (HPT)
      pain thresholds. Capsaicin-induced pain intensity was continuously rated on a 0
      10 electronic visual analogue scale (VAS). The area under the VAS curve (VASAUC)
      after rinsing was calculated for each solution. RESULTS: Capsaicin application on
      the tongue evoked burning pain with a peak of 4.8/10, and significantly increased
      CDT and MDT while significantly decreasing WDT, HPT, and MPT. The VASAUC was
      significantly smaller after oral rinse with 0.05 mol/L GABA, 0.5 mol/L GABA, and
      1% lidocaine than after oral rinse with water. Rinse with 0.5 mol/L or 0.05 mol/L
      GABA were similarly effective in decreasing VASAUC. Rinsing with either 1%
      lidocaine, 0.5 mol/L or 0.05 mol/L GABA also significantly attenuated the effects
      of capsaicin on WDT and HPT in a treatment independent manner. There were no sex
      related differences in these effects of GABA. CONCLUSIONS: Capsaicin-induced
      burning tongue pain and decreases in WDT and HPT can be ameliorated by rinsing
      the mouth with lidocaine and GABA solutions. SIGNIFICANCE: Rinsing the mouth with
      an oral GABA containing solution ameliorated burning pain and increased heat
      sensitivity produced by application of capsaicin to the tongue. This finding
      suggests that GABA can act as a local analgesic agent in the oral cavity.

PMID- 29024231
TI  - Chimeric thoracoacromial artery perforator flap for one-staged reconstruction of
      complex pharyngoesophageal defects: A single unit experience.
AB  - BACKGROUND: Circumferential hypopharyngeal defects with anterior neck skin loss
      often require double-stacked or chimeric flaps to achieve good surgical outcomes.
      The thoracoacromial artery perforator (TAAP) flap is a simple and reliable method
      for hypopharyngeal defect reconstruction. METHODS: From March 2012 to February
      2015, 19 male patients with an average age of 62 years (range 42-81 years)
      underwent complex pharyngoesophageal defect reconstruction with chimeric TAAP
      flaps. RESULTS: All 19 male patients who underwent reconstruction with TAAP flaps
      achieved optimal functional outcomes. All donor sites were closed primarily. The
      average length of hospital stay was 12.5 days (range 10-19 days). All patients
      returned back to normal nutrition after 8 weeks postoperatively. The average
      follow-up period was 19.3 months (range 14-48 months). CONCLUSION: The chimeric
      TAAP flap is an innovative local alternative solution for reconstruction of
      complex circumferential hypopharyngeal defects when free tissue transfer is
      contraindicated or neck vessels are depleted.

PMID- 29024232
TI  - Social constraints and psychological well-being after prostate cancer: A follow
      up at 12 and 24 months after surgery.
AB  - OBJECTIVE: Studies indicate that social constraints (barriers to emotional
      expression) may be a risk factor for psychological morbidity. We aimed to
      investigate the association between prostate cancer-related social constraints
      and psychological well-being following prostate cancer surgery. METHODS: In a
      group of 3478 partnered patients, participating in the Laparoscopic Prostatectomy
      Robot Open trial, a prospective multicenter comparative study of robot-assisted
      laparoscopic and retropubic radical prostatectomy for prostate cancer, we used
      log-binomial regression analysis to investigate the links between prostate cancer
      related social constraints at 3 months after surgery and psychological well-being
      at 12 and 24 months. RESULTS: A total of 1086 and 1093 men reported low well
      being at 12 and 24 months, respectively. Prostate cancer-related social
      constraints by partner predicted low psychological well-being at 12 months
      (adjusted RR: 1.4; 95% CI, 1.1-1.9) and by others (adjusted RR: 1.9; 95% CI, 1.1
      3.5). Intrusive thoughts mediated the association. CONCLUSIONS: Negative
      responses from the social environment, especially from partner to talking about
      the prostate cancer experience affected patients' psychological well-being 2
      years after radical prostatectomy. Results emphasize the importance of helping
      patients mobilize psychosocial resources within their social network, especially
      among those with a lack of quality psychosocial support.

PMID- 29024234
TI  - Vicariously touching products through observing others' hand actions increases
      purchasing intention, and the effect of visual perspective in this process: An
      fMRI study.
AB  - The growth of online shopping increases consumers' dependence on vicarious
      sensory experiences, such as observing others touching products in commercials.
      However, empirical evidence on whether observing others' sensory experiences
      increases purchasing intention is still scarce. In the present study,
      participants observed others interacting with products in the first- or third
      person perspective in video clips, and their neural responses were measured with
      functional magnetic resonance imaging (fMRI). We investigated (1) whether and how
      vicariously touching certain products affected purchasing intention, and the
      neural correlates of this process; and (2) how visual perspective interacts with
      vicarious tactility. Vicarious tactile experiences were manipulated by hand
      actions touching or not touching the products, while the visual perspective was
      manipulated by showing the hand actions either in first- or third-person
      perspective. During the fMRI scanning, participants watched the video clips and
      rated their purchasing intention for each product. The results showed that,
      observing others touching (vs. not touching) the products increased purchasing
      intention, with vicarious neural responses found in mirror neuron systems (MNS)
      and lateral occipital complex (LOC). Moreover, the stronger neural activities in
      MNS was associated with higher purchasing intention. The effects of visual
      perspectives were found in left superior parietal lobule (SPL), while the
      interaction of tactility and visual perspective was shown in precuneus and
      precuneus-LOC connectivity. The present study provides the first evidence that
      vicariously touching a given product increased purchasing intention and the
      neural activities in bilateral MNS, LOC, left SPL and precuneus are involved in
      this process. Hum Brain Mapp 39:332-343, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29024233
TI  - Use of D-dimer measurement to guide anticoagulant treatment in recurrent
      pregnancy loss associated with antiphospholipid syndrome.
AB  - PROBLEM: To examine whether the level of plasma D-dimer can guide anticoagulant
      treatment in recurrent pregnancy loss (RPL) associated with antiphospholipid
      syndrome (APS). METHODS: A total of 1096 RPL women with APS between 2012 and 2015
      in a single-center hospital were randomly divided into two groups (group A, 75 mg
      of low-dose aspirin [LDA] daily; group B, 75 mg of LDA plus 4100 U of low
      molecular weight heparin [LMWH] subcutaneously daily); 1015 of the total
      successfully completed the trial. Plasma D-dimer level and live birth rates were
      estimated. RESULTS: For APS women with an elevated D-dimer level at baseline,
      higher live birth rates were reached in LDA plus LMWH group compared to LDA alone
      group (92.71% vs 61.68%, P < .0001); however, no significant differences were
      found between the two groups of women with a normal D-dimer level (87.08% vs
      83.76%, P = .48). Women with a normal D-dimer level at all blood draw points had
      the highest live birth rates (92.88%), as compared with those with persistently
      abnormal D-dimer at all blood draw points or increased D-dimer level after
      treatment (P < .001). CONCLUSION: The combination therapy with LDA and LMWH is
      not essential for all APS women, but has proven to be beneficial for women with
      an elevated D-dimer level.

PMID- 29024236
TI  - Mesenchymal Stromal Cell-Derived Extracellular Vesicles Provide Long-Term
      Survival After Total Body Irradiation Without Additional Hematopoietic Stem Cell
      Support.
AB  - The therapeutic effect of mesenchymal stromal cells (MSC) in tissue regeneration
      is based mainly on the secretion of bioactive molecules. Here, we report that the
      radioprotective effect of mouse bone marrow derived mesenchymal stromal cells
      (mMSC) can be attributed to extracellular vesicles (EV) released from mMSC. The
      transplantation of mMSC-derived EV into lethally irradiated mice resulted in long
      term survival but no improvement in short-term reconstitution of the recipients.
      Importantly, the radiation rescue was efficient without additional hematopoietic
      support. In vitro we show a protection by EV of irradiated hematopoietic stem
      cells but not progenitor cells using stroma-cell cultures and colony-forming
      assays. After systemic infusion into lethally irradiated recipients, labeled EV
      traveled freely through the body reaching the bone marrow within 2 hours. We
      further show that long-term repopulating Sca-1 positive and c-kit low-positive
      stem cells were directly targeted by EV leading to long-term survival.
      Collectively, our data suggest EV as an effective first-line treatment to combat
      radiation-induced hematopoietic failure which might also be helpful in
      alleviating myelosuppression due to chemotherapy and toxic drug reaction. We
      suggest the infusion of MSC-derived EV as efficient and immediate treatment
      option after irradiation injuries. Stem Cells 2017;35:2379-2389.

PMID- 29024237
TI  - Sterol content in the artificial diet of Mythimna separata affects the
      metabolomics of Arma chinensis (Fallou) as determined by proton nuclear magnetic
      resonance spectroscopy.
AB  - Insects cannot synthesize sterols and must obtain them from plants. Therefore,
      reducing plant sterol content or changing sterol type might be an effective pest
      control strategy. However, the impacts of these changes on pests' natural
      predators remain unknown. Here, we fed artificial diets with reduced sterol
      content to Mythimna separata (Walker) (Lepidoptera: Noctuidae) and investigated
      the effects on its natural predator, Arma chinensis (Fallou) (Hemiptera:
      Pentatomidae). Reduced sterol content in M. separata (MS1, MS2, and MS5) was
      achieved by feeding them artificial diets prepared from a feed base subjected to
      one, two, or five cycles of sterol extractions, respectively. The content of most
      substances increased in A. chinensis (AC) groups feeding on MS2 and MS5. The
      content of eight substances (alanine, betaine, dimethylamine, fumarate,
      glutamine, glycine, methylamine, and sarcosine) differed significantly between
      the control (AC0) and treated (AC1, AC2, and AC5) groups. Metabolic profiling
      revealed that only AC5 was significantly distinct from AC0; the major substances
      contributing to this difference were maltose, glucose, tyrosine, proline, O
      phosphocholine, glutamine, allantoin, lysine, valine, and glutamate. Furthermore,
      only two metabolic pathways, that is, nicotinate and nicotinamide metabolism and
      ubiquinone and other terpenoid-quinone biosynthesis, differed significantly
      between AC1 and AC5 and the control, albeit with an impact value of zero. Thus,
      the sterol content in the artificial diet fed to M. separata only minimally
      affected the metabolites and metabolic pathways of its predator A. chinensis,
      suggesting that A. chinensis has good metabolic self-regulation with high
      resistance to sterol content changes.

PMID- 29024238
TI  - Size- and Interface-Modulated Metal-Insulator Transition in Solution-Synthesized
      Nanoscale VO2 -TiO2 -VO2 Heterostructures.
AB  - The M1 form of vanadium dioxide, which exhibits a reversible insulator-metal
      transition above room temperature, has been incorporated into nanoscale
      heterostructures through solution-phase epitaxial growth on the tips of rutile
      TiO2 nanorods. Four distinct classes of VO2 -TiO2 -VO2 nanorod heterostructures
      are accessible by modulating the growth conditions. Each type of VO2 -TiO2 -VO2
      nanostructure has a different insulator-metal transition temperature that depends
      on the VO2 domain sizes and the TiO2 -VO2 interfacial strain characteristics.

PMID- 29024235
TI  - Topography and timing of activity in right inferior frontal cortex and anterior
      insula for stopping movement.
AB  - Stopping incipient action activates both the right inferior frontal cortex (rIFC)
      and the anterior insula (rAI). Controversy has arisen as to whether these
      comprise a unitary cortical cluster-the rIFC/rAI-or whether rIFC is the primary
      stopping locus. To address this, we recorded directly from these structures while
      taking advantage of the high spatiotemporal resolution of closely spaced stereo
      electro-encephalographic (SEEG) electrodes. We studied 12 patients performing a
      stop-signal task. On each trial they initiated a motor response (Go) and tried to
      stop to an occasional stop signal. Both the rIFC and rAI exhibited an increase in
      broadband gamma activity (BGA) after the stop signal and within the time of
      stopping (stop signal reaction time, SSRT), regardless of the success of
      stopping. The proportion of electrodes with this response was significantly
      greater in the rIFC than the rAI. Also, the rIFC response preceded that in the
      rAI. Last, while the BGA increase in rIFC occurred mainly prior to SSRT, the rAI
      showed a sustained increase in the beta and low gamma bands after the SSRT. In
      summary, the rIFC was activated soon after the stop signal, prior to and more
      robustly than the rAI, which on the other hand, showed a more prolonged response
      after the onset of stopping. Our results are most compatible with the notion that
      the rIFC is involved in triggering outright stopping in concert with a wider
      network, while the rAI is likely engaged by other processes, such as arousal,
      saliency, or behavioral adjustments. Hum Brain Mapp 39:189-203, 2018. (c) 2017
      Wiley Periodicals, Inc.

PMID- 29024239
TI  - Phosphorylation-Responsive Membrane Transport of Peptides.
AB  - Phosphorylation and dephosphorylation of peptides by kinases and phosphatases is
      essential for signal transduction in biological systems, and many diseases
      involve abnormal activities of these enzymes. Herein, we introduce amphiphilic
      calixarenes as key components for supramolecular, phosphorylation-responsive
      membrane transport systems. Dye-efflux experiments with liposomes demonstrated
      that calixarenes are highly active counterion activators for established cell
      penetrating peptides, with EC50 values in the low nanomolar range. We have now
      found that they can even activate membrane transport of short peptide substrates
      for kinases involved in signal transduction, whereas the respective
      phosphorylated products are much less efficiently transported. This allows
      regulation of membrane transport activity by protein kinase A (PKA) and protein
      kinase C (PKC), as well as monitoring of their activity in a label-free kinase
      assay.

PMID- 29024240
TI  - Total Synthesis of Lycoricidine and Narciclasine by Chemical Dearomatization of
      Bromobenzene.
AB  - The total synthesis of lycoricidine and narciclasine is enabled by an arenophile
      mediated dearomative dihydroxylation of bromobenzene. Subsequent transpositive
      Suzuki coupling and cycloreversion deliver a key biaryl dihydrodiol intermediate,
      which is rapidly converted into lycoricidine through site-selective syn-1,4
      hydroxyamination and deprotection. The total synthesis of narciclasine is
      accomplished by the late-stage, amide-directed C-H hydroxylation of a
      lycoricidine intermediate. Moreover, the general applicability of this strategy
      to access dihydroxylated biphenyls is demonstrated with several examples.

PMID- 29024241
TI  - Sentinel node biopsy in ductal carcinoma in situ of the breast: Never justified?
AB  - Sentinel lymph node biopsy for ductal carcinoma in situ (DCIS) of the breast is
      not standard of care. However, nodal involvement for DCIS patients is reported.
      Aim of our study was to identify preoperative features predictive of nodal
      involvement in DCIS patients. We have retrospectively reviewed 175 patients with
      a preoperative diagnosis of DCIS following a vacuum-assisted breast biopsy, and
      undergoing surgery with sentinel node biopsy. Variables distribution was compared
      between patients upstaged to invasive cancer at final pathology and patients with
      a confirmed DCIS, and between positive vs negative sentinel node patients.
      Univariate and multivariate analyses were performed for risk of a positive node.
      Lymph node biopsy was positive in 13 (7.4%) patients, with 8 (61.5%)
      macrometastases and 5 (38.5%) micrometastases. In these patients, Breast Imaging
      Reporting and Data System (BI-RADS) index >4 (OR 4.69, 95% CI 1.282-17.224, P =
      .02), lesion extension >=20 mm (OR 4.25, 95% CI 1.255-14.447, P = .02),
      multifocal disease (OR 4.12, 95% CI 0.987-17.174, P = .05), comedo type (OR 3.54,
      95% CI 1.044-11.969, P = .04), and upstaging (OR 4.56, 95% CI 1.080-19.249, P =
      .04) were all predictive of nodal involvement, although upstaging could not be
      predicted preoperatively. By multivariate analysis, the only independent factor
      predictive for positive sentinel node was multifocal disease (OR 5.14, 95% CI
      1.015-26.066, P < .05). A preoperative diagnosis of DCIS, also including advanced
      biopsy systems such as vacuum-assisted breast biopsy, may be not always
      sufficient to exclude patients from sentinel node biopsy. DCIS patients with
      associated BI-RADS >4, lesion extension >=20 mm, comedo type, and above all
      multifocal disease should be considered for axillary evaluation.

PMID- 29024242
TI  - Lanthanide-Based T2ex and CEST Complexes Provide Insights into the Design of pH
      Sensitive MRI Agents.
AB  - The CEST and T1 /T2 relaxation properties of a series of Eu3+ and Dy3+ DOTA
      tetraamide complexes with four appended primary amine groups are measured as a
      function of pH. The CEST signals in the Eu3+ complexes show a strong CEST signal
      after the pH was reduced from 8 to 5. The opposite trend was observed for the
      Dy3+ complexes where the r2ex of bulk water protons increased dramatically from
      ca. 1.5 mm-1  s-1 to 13 mm-1  s-1 between pH 5 and 9 while r1 remained unchanged.
      A fit of the CEST data (Eu3+ complexes) to Bloch theory and the T2ex data (Dy3+
      complexes) to Swift-Connick theory provided the proton-exchange rates as a
      function of pH. These data showed that the four amine groups contribute
      significantly to proton-catalyzed exchange of the Ln3+ -bound water protons even
      though their pKa 's are much higher than the observed CEST or T2ex effects. This
      demonstrated the utility of using appended acidic/basic groups to catalyze
      prototropic exchange for imaging tissue pH by MRI.

PMID- 29024243
TI  - Low clinical conversion rate in clinically isolated syndrome patients -
      diagnostic benefit of McDonald 2010 criteria?
AB  - BACKGROUND AND PURPOSE: New diagnostic criteria of multiple sclerosis (MS)
      increase the number of patients being diagnosed with MS whilst a substantial part
      might not convert to clinically definite MS (CDMS). The diagnostic accuracy of
      the McDonald 2005 and 2010 criteria for conversion to CDMS was evaluated in an
      unselected cohort of patients in whom an MS diagnostic work-up was decided.
      METHODS: Clinical, magnetic resonance imaging and cerebrospinal fluid data were
      analysed for all patients who presented with symptoms suspicious for MS at the
      university based MS outpatient clinic between 2006 and 2010 (n = 165). RESULTS:
      Follow-up was available for 131 patients. During the mean follow-up period of 2
      years, 19% of patients developed CDMS whereas 64% of the patients fulfilling
      McDonald 2010 criteria did not convert to CDMS. CONCLUSION: The low clinical
      conversion rate indicates that the new diagnostic criteria may increase the
      incidence of MS cases with a less active disease course.

PMID- 29024244
TI  - Local Chemical Stimulation of Neurons with the Fluidic Force Microscope
      (FluidFM).
AB  - Physiological communication between neurons is dependent on the exchange of
      neurotransmitters at the synapses. Although this chemical signal transmission
      targets specific receptors and allows for subtle adaptation of the action
      potential, in vitro neuroscience typically relies on electrical currents and
      potentials to stimulate neurons. The electric stimulus is unspecific and the
      confinement of the stimuli within the media is technically difficult to control
      and introduces large artifacts in electric recordings of the activity. Here, we
      present a local chemical stimulation platform that resembles in vivo
      physiological conditions and can be used to target specific receptors of
      synapses. Neurotransmitters were dispensed using the force-controlled fluidic
      force microscope (FluidFM) nanopipette, which provides exact positioning and
      precise liquid delivery. We show that controlled release of the excitatory
      neurotransmitter glutamate induces spiking activity in primary rat hippocampal
      neurons, as measured by concurrent electrical and optical recordings using a
      microelectrode array and a calcium-sensitive dye, respectively. Furthermore, we
      characterized the glutamate dose response of neurons by applying stimulation
      pulses of glutamate with concentrations from 0 to 0.5 mm. This new stimulation
      approach, which combines FluidFM for gentle and precise positioning with a
      microelectrode array read-out, makes it possible to modulate the activity of
      individual neurons chemically and simultaneously record their induced activity
      across the entire neuronal network. The presented platform not only offers a more
      physiological alternative compared with electrical stimulation, but also provides
      the possibility to study the effects of the local application of neuromodulators
      and other drugs.

PMID- 29024245
TI  - hace1 Influences zebrafish cardiac development via ROS-dependent mechanisms.
AB  - BACKGROUND: In this study, we reveal a previously undescribed role of the HACE1
      (HECT domain and Ankyrin repeat Containing E3 ubiquitin-protein ligase 1) tumor
      suppressor protein in normal vertebrate heart development using the zebrafish
      (Danio rerio) model. We examined the link between the cardiac phenotypes
      associated with hace1 loss of function to the expression of the Rho small family
      GTPase, rac1, which is a known target of HACE1 and promotes ROS production via
      its interaction with NADPH oxidase holoenzymes. RESULTS: We demonstrate that loss
      of hace1 in zebrafish via morpholino knockdown results in cardiac deformities,
      specifically a looping defect, where the heart is either tubular or "inverted".
      Whole-mount in situ hybridization of cardiac markers shows distinct abnormalities
      in ventricular morphology and atrioventricular valve formation in the hearts of
      these morphants, as well as increased expression of rac1. Importantly, this
      phenotype appears to be directly related to Nox enzyme-dependent ROS production,
      as both genetic inhibition by nox1 and nox2 morpholinos or pharmacologic rescue
      using ROS scavenging agents restores normal cardiac structure. CONCLUSIONS: Our
      study demonstrates that HACE1 is critical in the normal development and proper
      function of the vertebrate heart via a ROS-dependent mechanism. Developmental
      Dynamics 247:289-303, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29024247
TI  - CacyBP/SIP inhibits the migration and invasion behaviors of glioblastoma cells
      through activating Siah1 mediated ubiquitination and degradation of cytoplasmic
      p27.
AB  - Calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP) has been
      reported to be up-regulated and plays an important role in promoting cell
      proliferation in human glioma. However, the effect of CacyBP/SIP on glioma cell
      motility is still unclear. Here, to our surprise, CacyBP/SIP was found to inhibit
      the migration and invasion of glioma cells U251 and U87. Silencing of CacyBP/SIP
      significantly promoted the migration and invasion behaviors of glioma cells. On
      the contrary, overexpression of CacyBP/SIP obviously suppressed them. Further
      investigation indicated that silencing of CacyBP/SIP significantly reduced the
      interaction between Siah1 and cytoplasmic p27, which in turn attenuated the
      ubiquitination and degradation of cytoplasmic p27. In contrast, overexpression of
      CacyBP/SIP promoted the interaction between Siah1 and cytoplasmic p27, which in
      turn increased the ubiquitination and degradation of cytoplasmic p27.
      Importantly, the degradation of p27 could be blocked by Siah1 knockdown. Finally,
      we found that CacyBP/SIP was reversely related to cytoplasmic p27 in human normal
      brain tissues and glioma tissues. Taken together, these results suggest that
      CacyBP/SIP plays an important role in inhibiting glioma cell migration and
      invasion through promoting the degradation of cytoplasmic p27.

PMID- 29024246
TI  - PixelDB: Protein-peptide complexes annotated with structural conservation of the
      peptide binding mode.
AB  - PixelDB, the Peptide Exosite Location Database, compiles 1966 non-redundant, high
      resolution structures of protein-peptide complexes filtered to minimize the
      impact of crystal packing on peptide conformation. The database is organized to
      facilitate study of structurally conserved versus non-conserved elements of
      protein-peptide engagement. PixelDB clusters complexes based on the structural
      similarity of the peptide-binding protein, and by comparing complexes within a
      cluster highlights examples of domains that engage peptides using more than one
      binding mode. PixelDB also identifies conserved peptide core structural motifs
      characteristic of each binding mode. Peptide regions that flank core motifs often
      make non-structurally conserved interactions with the protein surface in regions
      we call exosites. Many examples establish that exosite contacts can be important
      for enhancing protein binding and interaction specificity. PixelDB provides a
      resource for computational and structural biologists to study, model, and predict
      core-motif and exosite-contacting peptide interactions. PixelDB is available to
      the community without restriction in a convenient flat-file format with
      accompanying visualization tools.

PMID- 29024248
TI  - Precise Assembly of Particles for Zigzag or Linear Patterns.
AB  - Precise control of particles assembly has tremendous potential for fabricating
      intricate structures and functional materials. However, it is still a challenge
      to achieve one-dimensional assembly with precisely controlled morphology. An
      effective strategy is reported to precisely assemble particles into well-defined
      patterns by liquid confinement through controlling the viscosity of the assembly
      system. It is found that high viscosity of the system impedes particles
      rearrangement and facilitates the generation of zigzag or twined zigzag assembly
      structures, while low viscosity of the system allows particles to rearrange into
      linear or zipper structures driven by lowering the surface deformation of the
      liquid. As a result, precise control of different assembly patterns can be
      achieved through tuning the viscosity of solvent and size confinement ratios.
      This facile approach shows generality for particles assembly of different sizes
      and materials.

PMID- 29024249
TI  - Bone Strength in Girls and Boys After a Distal Radius Fracture: A 2-Year HR-pQCT
      Double Cohort Study.
AB  - We recently reported impaired bone strength in girls with low- to moderate-energy
      distal radius fractures (Fx) compared with girls with no history of forearm
      fractures (Non-Fx). We aimed to determine whether bone strength deficits observed
      at baseline were still present after 2 years. We assessed bone strength,
      microarchitecture, and bone mineral density (BMD) of the non-fractured (Fx) and
      non-dominant (Non-Fx) distal radius (7% site) at baseline, 12, and 24 months
      using high-resolution pQCT (Scanco Medical, Bruttisellen, Switzerland) in 104
      girls (aged 11.0 +/- 1.7 years; 47 Fx, 57 Non-Fx) and 157 boys (aged 12.7 +/- 1.7
      years; 86 Fx, 71 Non-Fx). Bone outcomes included total area (Tt.Ar) and bone
      mineral density (Tt.BMD), trabecular bone volume ratio (BV/TV), thickness
      (Tb.Th), separation (Tb.Sp), and number (Tb.N), and cortical BMD (Ct.BMD),
      thickness (Ct.Th), and porosity (Ct.Po). We used finite element analysis to
      estimate bone strength (failure load [F.Load]; ultimate stress [U.Stress]; load
      to-strength ratio). We used sex-specific mixed-effects models to compare bone
      outcomes between Fx and Non-Fx over 2 years. In girls, those with fractures had
      18% to 24% lower U.Stress and 5% to 9% lower Tt.BMD than Non-Fx at all time
      points (p < 0.017). In secondary analysis by fracture degree, girls with low
      energy (LE) fractures had 19% to 21% lower F.Load, 25% to 47% lower U.Stress, 11%
      to 14% lower Tt.BMD, and 11% to 15% lower BV/TV than Non-Fx at all time points (p
      < 0.017). In contrast, boys' bone outcomes were similar between Fx and Non-Fx at
      all time points. In secondary analysis by fracture degree, boys with LE fractures
      had 10% lower Tt.BMD and 10% lower Ct.Th compared with Non-Fx at 12 months only.
      Deficits in distal radius bone strength and trabecular bone microarchitecture
      appear to track across 2 years after a forearm fracture in girls but not in boys.
      Longer follow-up is needed to determine whether deficits persist into adulthood
      in women and how they may influence future risk of fragility fracture. (c) 2017
      American Society for Bone and Mineral Research.

PMID- 29024250
TI  - Non-invasive detection of bladder cancer via expression-targeted gene delivery.
AB  - BACKGROUND: Because of the time and expense associated with the procedures and
      possible distress to the patient, cystoscopy or other imaging techniques are
      typically not used for bladder cancer detection before symptoms become present.
      Alternatively, commercial assays for urinary tumor markers exist but are marred
      by low sensitivity and high cost. There is a need for a simple and sensitive
      means of tumor detection, such as via the analysis of urine. METHODS: Plasmids
      encoding the secretable reporter Gaussia Luciferase (G.LUC), under the control of
      cmv, cox2 or opn promoters, were delivered via polyethylenimine into bladder
      tumor cells in culture and into the bladders of mice. Expression profiles of the
      reporter were recorded, the optimal times for reporter detection were determined
      and the relationship of reporter expression with tumor size was calculated.
      RESULTS: In vitro results showed that both the cox2 and opn promoters can drive
      significant expression of G.LUC in bladder carcinoma cells in a targeted fashion.
      In vivo results demonstrated that the cox2 promoter caused expression of G.LUC at
      detectable levels in the urine, with local signal maxima occurring at 48 and 72 h
      post-transfection. G.LUC levels in the urine had a 24-h periodicity, with the
      periodicity partly being the result of an agent secreted by tumor cells that
      served to mask the luciferase signal. CONCLUSIONS: Having shown tumor specificity
      and having been calibrated with respect to circadian expression patterns, the
      detection system shows great promise for future investigation of tumor presence
      both in the urinary bladder and other models of cancer.

PMID- 29024251
TI  - Enzymatic Incorporation of Modified Purine Nucleotides in DNA.
AB  - A series of nucleotide analogues, with a hypoxanthine base moiety (8
      aminohypoxanthine, 1-methyl-8-aminohypoxanthine, and 8-oxohypoxanthine), together
      with 5-methylisocytosine were tested as potential pairing partners of N8 
      glycosylated nucleotides with an 8-azaguanine or 8-aza-9-deazaguanine base moiety
      by using DNA polymerases (incorporation studies). The best results were obtained
      with the 5-methylisocytosine nucleotide followed by the 1-methyl-8
      aminohypoxanthine nucleotide. The experiments demonstrated that small differences
      in the structure (8-azaguanine versus 8-aza-9-deazaguanine) might lead to
      significant differences in recognition efficiency and selectivity, base pairing
      by Hoogsteen recognition at the polymerase level is possible, 8-aza-9
      deazaguanine represents a self-complementary base pair, and a correlation exists
      between in vitro incorporation studies and in vivo recognition by natural bases
      in Escherichia coli, but this recognition is not absolute (exceptions were
      observed).

PMID- 29024252
TI  - Revision gastric bypass after laparoscopic adjustable gastric band: a 10-year
      experience at a public teaching hospital.
AB  - BACKGROUND: In Australia, there is limited access to public revisional bariatric
      procedures. However, the need for such procedures is rising. We investigated the
      safety and efficacy of band-to-bypass procedures in our experience at a public
      teaching hospital over a period of 10 years. METHODS: Using a prospectively
      maintained bariatric surgical database, we analysed 91 consecutive planned band
      to-bypass procedures from 2007 to November 2016. All patients had prior
      laparoscopic adjustable gastric bands removed and formation of Roux-en-Y gastric
      bypass, in one or two stages. Primary outcomes were 30-day complication rate and
      excess weight loss from 12 months. The impact of fellows as primary operators on
      these outcomes was assessed. RESULTS: Eighty-two patients met the inclusion
      criteria. Seventy-one (84.5%) were females. Mean age was 48.8 years (SD: 8.85).
      Immediate post-operative complications included six (7.3%) patients with
      gastrojejunostomy leak, three of whom required conversion to laparotomy, with one
      mortality (1.22%). Fifty-two patients had follow-up of 1 year or more (median:
      2.36, range: 1-9.24). Mean excess weight loss at the end of follow-up was 52.79%
      (SD: 46.46). Twenty-eight (34.14%) cases were performed primarily by a fellow
      under the guidance of an experienced bariatric surgeon, with equivalent results.
      CONCLUSION: Revisional band-to-bypass in the public setting is an effective but
      complex procedure associated with morbidity. Some risk may be ameliorated by
      development of selection criteria to exclude certain high-risk groups. We hope
      discussion amongst other bariatric groups will further refine this approach.

PMID- 29024253
TI  - Prerequisites of Isopeptide Bond Formation in Microcystin Biosynthesis.
AB  - The biosynthesis of the potent cyanobacterial hepatotoxin microcystin involves
      isopeptide bond formation through the carboxylic acid side chains of d-glutamate
      and beta-methyl d-aspartate. Analysis of the in vitro activation profiles of the
      two corresponding adenylation domains, McyE-A and McyB-A2 , either in a didomain
      or a tridomain context with the cognate thiolation domain and the upstream
      condensation domain revealed that substrate activation of both domains strictly
      depended on the presence of the condensation domains. We further identified two
      key amino acids in the binding pockets of both adenylation domains that could
      serve as a bioinformatic signature of isopeptide bond-forming modules
      incorporating d-glutamate or d-aspartate. Our findings further contribute to the
      understanding of the multifaceted role of condensation domains in nonribosomal
      peptide synthetase assembly lines.

PMID- 29024254
TI  - O2 Activation on Ceria Catalysts-The Importance of Substrate Crystallographic
      Orientation.
AB  - An atomic-level understanding of dioxygen activation on metal oxides remains one
      of the major challenges in heterogeneous catalysis. By performing a thorough
      surface-science study of all three low-index single-crystal surfaces of ceria,
      probably the most important redox catalysts, we provide a direct spectroscopic
      characterization of reactive dioxygen species at defect sites on the reduced
      ceria (110) and (100) surfaces. Surprisingly, neither of these superoxo and
      peroxo species was found on ceria (111), the thermodynamically most stable
      surface of this oxide. Applying density functional theory, we could relate these
      apparently inconsistent findings to a sub-surface diffusion of O vacancies on
      (111) substrates, but not on the less-closely packed surfaces. These observations
      resolve a long standing debate concerning the location of O vacancies on ceria
      surfaces and the activation of O2 on ceria powders.

PMID- 29024255
TI  - Deficiency of the melanin biosynthesis genes SCD1 and THR1 affects sclerotial
      development and vegetative growth, but not pathogenicity, in Sclerotinia
      sclerotiorum.
AB  - The fungus Sclerotinia sclerotiorum is a necrotrophic plant pathogen causing
      significant damage on a broad range of crops. This fungus produces sclerotia that
      serve as the long-term survival structures in the life cycle and the primary
      inoculum in the disease cycle. Melanin plays an important role in protecting
      mycelia and sclerotia from ultraviolet radiation and other adverse environmental
      conditions. In this study, two genes, SCD1 encoding a scytalone dehydratase and
      THR1 encoding a trihydroxynaphthalene reductase, were disrupted by target gene
      replacement, and their roles in mycelial growth, sclerotial development and
      fungal pathogenicity were investigated. Phylogenetic analyses indicated that the
      deduced amino acid sequences of SCD1 and THR1 were similar to the orthologues of
      Botrytis cinerea. Expression of SCD1 was at higher levels in sclerotia relative
      to mycelia. THR1 was expressed at similar levels in mycelia and sclerotia at
      early stages, but was up-regulated in sclerotia at the maturation stage.
      Disruption of SCD1 or THR1 did not change the pathogenicity of the fungus, but
      resulted in slower radial growth, less biomass, wider angled hyphal branches,
      impaired sclerotial development and decreased resistance to ultraviolet light.

PMID- 29024257
TI  - Active Cocatalysts for Photocatalytic Hydrogen Evolution Derived from Nickel or
      Cobalt Amine Complexes.
AB  - A cost-effective and robust strategy for the anchoring of molecular hydrogen
      evolution cocatalysts onto semiconductors has recently been reported. The
      composite materials were highly efficient and stable towards photocatalytic H2
      evolution. This study provides guidance for the design and construction of highly
      active heterogeneous photocatalysts.

PMID- 29024256
TI  - Transgenerational plasticity and climate change experiments: Where do we go from
      here?
AB  - Phenotypic plasticity, both within and across generations, is an important
      mechanism that organisms use to cope with rapid climate change. While an
      increasing number of studies show that plasticity across generations
      (transgenerational plasticity or TGP) may occur, we have limited understanding of
      key aspects of TGP, such as the environmental conditions that may promote it, its
      relationship to within-generation plasticity (WGP) and its role in evolutionary
      potential. In this review, we consider how the detection of TGP in climate change
      experiments is affected by the predictability of environmental variation, as well
      as the timing and magnitude of environmental change cues applied. We also discuss
      the need to design experiments that are able to distinguish TGP from selection
      and TGP from WGP in multigenerational experiments. We conclude by suggesting
      future research directions that build on the knowledge to date and admit the
      limitations that exist, which will depend on the way environmental change is
      simulated and the type of experimental design used. Such an approach will open up
      this burgeoning area of research to a wider variety of organisms and allow better
      predictive capacity of the role of TGP in the response of organisms to future
      climate change.

PMID- 29024258
TI  - Non-Enzymatic Oxidation of a Pentagalloylglucose Analogue into Members of the
      Ellagitannin Family.
AB  - The occurrence of more than 1000 structurally diverse ellagitannins has been
      hypothesized to begin with the oxidation of penta-O-galloyl-beta-d-glucose (beta
      PGG) for the coupling of the galloyl groups. However, the non-enzymatic behavior
      of beta-PGG in the oxidation is unknown. Disclosed herein is which galloyl groups
      tended to couple and which axial chirality was predominant in the derived
      hexahydroxydiphenoyl groups when an analogue of beta-PGG was subjected to
      oxidation. The galloyl groups coupled in the following order: at the 4,6-, 1,6-,
      1,2-, 2,3-, and 3,6-positions with respective S-, S-, R-, S-, and R-axial
      chirality. Among them, the most preferred 4,6-coupling reflected the what was
      observed for natural ellagitannins. A new finding was that the second best
      coupling occured at the 1,6-positions. With the detection of a 3,6-coupled
      product, this work demonstrated that even ellagitannin skeletons with an axial
      rich glucose core may be generated non-enzymatically.

PMID- 29024259
TI  - Selective Radical Fluorination of Tertiary Alkyl Halides at Room Temperature.
AB  - Direct fluorination of tertiary alkyl bromides and iodides with Selectfluor is
      described. The halogen-exchange fluorination proceeds efficiently in acetonitrile
      at room temperature under metal-free conditions and exhibits a wide range of
      functional group compatibility. Furthermore, the reactions are highly selective
      in that alkyl chlorides and primary and secondary alkyl bromides remain intact. A
      radical mechanism is proposed for this selective fluorination.

PMID- 29024260
TI  - Atrial fibrillation in heart failure with preserved ejection fraction: time to
      address the chicken and the egg.

PMID- 29024261
TI  - Pathologic significance of a novel oncoprotein in thyroid cancer progression.
AB  - BACKGROUND: The incidence of thyroid cancer is increasing worldwide, and there is
      an emerging need to develop accurate tools for diagnosis. Fine needle aspiration
      biopsy has greatly improved evaluation of thyroid nodules, but challenges with
      indeterminate lesions remain in up to 25% of biopsies. Novel tissue biomarkers
      may assist in improved nodule characterization. Microcalcifications occurring in
      thyroid cancers suggest proteins involved in bone formation may play a role in
      thyroid carcinogenesis. We evaluated the expression of the known osteogenic
      protein, Enigma, in thyroid cancer as a candidate oncoprotein and role in
      carcinogenesis based on association with other known oncoproteins such as bone
      morphogenetic protein-1 (BMP-1). METHODS: The expression of both Enigma and BMP-1
      were evaluated by immunohistochemistry (IHC) in an equal number of benign (n =
      120) and different histological subtypes of malignant (n = 120) human archival
      thyroid nodules with and without calcification. The colocalization of Enigma with
      BMP-1 was evaluated by confocal microscopy using the BZ analyzer. RESULTS: Enigma
      was strongly expressed in thyroid cancer tissue with a higher immunoreactive
      score in advanced thyroid cancer compared to less advanced and benign nodules.
      Enigma was localized either in cytoplasm or nucleus depending on the histological
      subtypes. Higher expression of Enigma was associated with the tumor size and
      lymph node involvement. There was clear and strong colocalization signal of
      Enigma and that of BMP-1. Expression of Enigma occurred without regard to
      calcification in cancer tissue. CONCLUSION: Enigma may serve as an oncoprotein
      marker, identifying benign from malignant thyroid tissue on FNA. Enigma may have
      a role in carcinogenesis of thyroid cancer independent of tissue calcification,
      possibly in relation to interaction with BMP-1.

PMID- 29024262
TI  - Ionic Self-Assembled Derivative of Tetraphenylethylene: Synthesis, Enhanced Solid
      State Emission, Liquid-Crystalline Structure, and Cu2+ Detection Ability.
AB  - A novel tetraphenylethylene complex composed of 4',4'',4''',4''''-(ethene-1,1,2,2
      tetrayl)tetrabiphenyl-4-carboxylic acid (H4 ETTC) and dimethyldioctadecylammonium
      bromide (DOAB) with enhanced solid-state emission is designed and synthesized
      through an ionic self-assembly (ISA) strategy. The aggregation-induced emission
      property, phase behavior, and supramolecular structure of the complex are
      characterized by a combination of experimental measurements. The experimental
      results reveal that the ISA complex can self-assemble into an ordered helical
      supramolecular structure with enhanced luminescent properties, although the ETTC
      cores possess extensive conjugation and high rigidity. Due to the prolonged
      conjugation length, the fluorescence quantum yield of ETTC-DOAB is boosted to 66
      %. Moreover, it is demonstrated that assemblies of the ISA complex are an
      effective sensor for Cu2+ . Owing to the disassembly modulation of ETTC-DOAB
      aggregations, the fluorescence emission of the assemblies can be selectively and
      sensitively quenched by Cu2+ , with a detection limit as low as 12.6 nm. The
      enhanced emission efficiency, in combination with the liquid crystallinity and
      superior sensing performance to Cu2+ , make the ETTC-DOAB complex a potential
      candidate for the fabrication of a luminescent device and chemosensor for Cu2+
      detection.

PMID- 29024263
TI  - Field Distribution of Transcranial Static Magnetic Stimulation in Realistic Human
      Head Model.
AB  - OBJECTIVE: The objective of this work was to characterize the magnetic field (B
      field) that arises in a human brain model from the application of transcranial
      static magnetic field stimulation (tSMS). MATERIALS AND METHODS: The spatial
      distribution of the B-field magnitude and gradient of a cylindrical, 5.08 cm *
      2.54 cm NdFeB magnet were simulated in air and in a human head model using the
      finite element method and calibrated with measurements in air. The B-field was
      simulated for magnet placements over prefrontal, motor, sensory, and visual
      cortex targets. The impact of magnetic susceptibility of head tissues on the B
      field was quantified. RESULTS: Peak B-field magnitude and gradient respectively
      ranged from 179-245 mT and from 13.3-19.0 T/m across the cortical targets. B
      field magnitude, focality, and gradient decreased with magnet-cortex distance.
      The variation in B-field strength and gradient across the anatomical targets
      largely arose from the magnet-cortex distance. Head magnetic susceptibilities had
      negligible impact on the B-field characteristics. The half-maximum focality of
      the tSMS B-field ranged from 7-12 cm3 . SIGNIFICANCE: This is the first
      presentation and characterization of the three-dimensional (3D) spatial
      distribution of the B-field generated in a human brain model by tSMS. These data
      can provide quantitative dosing guidance for tSMS applications across various
      cortical targets and subjects. The finding that the B-field gradient is high near
      the magnet edges should be considered in studies where neural tissue is placed
      close to the magnet. The observation that susceptibility has negligible effects
      confirms assumptions in the literature.

PMID- 29024264
TI  - Deutetrabenazine for tardive dyskinesia: A systematic review of the efficacy and
      safety profile for this newly approved novel medication-What is the number needed
      to treat, number needed to harm and likelihood to be helped or harmed?
AB  - OBJECTIVE: Deutetrabenazine is a deuterated formulation of tetrabenazine. The aim
      of this systematic review is to describe the efficacy, tolerability and safety of
      deutetrabenazine for the treatment of tardive dyskinesia (TD). DATA SOURCES: The
      pivotal registration trials were accessed by querying
      http://www.ncbi.nlm.nih.gov/pubmed/ and http://www.clinicaltrials.gov, for the
      search terms 'deutetrabenazine' OR 'SD-809', and by also querying the EMBASE
      (Elsevier) commercial database for clinical poster abstracts, and by asking the
      manufacturer for copies of posters presented at congresses. Product labelling
      provided additional information. STUDY SELECTION: All available clinical reports
      of studies were identified. DATA EXTRACTION: Descriptions of the principal
      results and calculation of number needed to treat (NNT) and number needed to harm
      (NNH) for relevant dichotomous outcomes were extracted from the available study
      reports and other sources of information. DATA SYNTHESIS: Deutetrabenazine, a
      reversible inhibitor of vesicular monoamine transporter type 2 (VMAT2), received
      approval for the treatment of TD in adults based on a clinical trial development
      programme that included two 12-week parallel group, randomised and placebo
      controlled studies. Deutetrabenazine dose is determined individually for each
      patient based on reduction of TD and tolerability. The recommended starting dose
      of deutetrabenazine for TD is 6 mg BID, administered with food, and can be
      increased at weekly intervals in increments of 6 mg/day to a maximum recommended
      daily dosage of 24 mg BID. The percentage of responders in the fixed-dose Phase
      III acute study, as defined by a rating of "much improved" or "very much
      improved" on the clinical global impression of change, was 46% for
      deutetrabenazine (pooled dose groups 12 and 18 mg BID) vs 26% for placebo,
      yielding a NNT of 5 (95% CI 3-19); the percentage of responders as defined by an
      improvement in Abnormal Involuntary Movement Scale (AIMS) severity score (sum of
      items 1-7) of 50% or more, was 34% for deutetrabenazine (pooled dose groups 12
      and 18 mg BID) vs 12% for placebo, yielding a NNT of 5 (95% CI 3-11). Pooling the
      data across both short-term studies, NNT for AIMS response for the therapeutic
      doses of deutetrabenazine vs placebo was 7 (95% CI 4-18). Discontinuation because
      of an adverse event occurred among 3.6% of patients randomised to
      deutetrabenazine (any dose) vs 3.1% for placebo, yielding a NNH of 189 (not
      significant). The Likelihood to be Helped or Harmed comparing success (AIMS
      response) vs discontinuation because of an adverse event is 27. The most common
      adverse reactions (that occurred in >=4% of deutetrabenazine-treated patients
      with TD and greater than placebo) were nasopharyngitis and insomnia, with NNH
      values of 50 (not significant) and 34 (95% CI 18-725), respectively. CONCLUSIONS:
      Deutetrabenazine is the second FDA-approved agent specifically indicated for the
      treatment of TD. Head-to-head comparisons with other VMAT2 inhibitors among
      patients with TD in the "real world" are needed.

PMID- 29024265
TI  - Effectiveness of a handmade "New Carotid Catheter" in transradial carotid
      angiography: A comparison with conventional multipurpose catheters.
AB  - OBJECTIVE: The incidence and severity of carotid atherosclerosis increases in
      proportion with coronary artery disease and its severity. A special catheter
      specifically used for transradial carotid angiography has not yet been marketed.
      In this study, we investigate the feasibility and safety of our carotid catheter,
      which was made by reshaping currently available catheters. METHODS: Between 2010
      and 2017, a total of 921 patients with indications for carotid angiography were
      identified after angiographic examinations and included in the study. Carotid
      angiography was performed in 403 patients (female, n = 161) using the 3.5 JL
      catheter, while in 518 (female, n = 207) patients, new catheters were employed.
      The new catheter was shaped like a hook in the laboratory with a heat gun.
      Demographic information and angiographic data from the patients in both groups
      were retrospectively analyzed. RESULTS: The baseline characteristics of both
      groups were comparable. When compared with the use of a 3.5 JL catheter, right
      transradial carotid angiographies performed with our new handmade catheter
      resulted in lesser amounts of opaque material used (55 mL vs 66 mL, P < 0.001)
      and shorter total fluoroscopy time, (3.60 +/- 1.85 min vs 3.14 +/- 1.55 min, P <
      0.001). The handmade catheter also resulted in a higher success rate of selective
      visualization (97% vs 40%, P < 0.001). Rates of minor complication were
      comparable between the two catheters (6.5% vs 6.6% P = 234). Neither permanent
      damage nor morbidity or mortality was observed in either arm. DISCUSSION:
      Currently available catheters and methods are inadequate for routine transradial
      carotid angiography. For routine transradial carotid angiography, innovatively
      designed catheters are required. The catheter we developed for transradial
      carotid angiography was more successful than the conventional catheter in
      obtaining satisfactory images. High quality images can be obtained with the newly
      designed catheters. CONCLUSION: Transradial carotid angiography can be performed
      using our newly developed carotid catheter. The carotid arteries of patients with
      widespread coronary artery disease can be visualized, while asymptomatic patients
      carrying a high risk of stroke can be treated, preventing potential stroke
      occurrence. In a larger-scale comparative study, the favorable contributions of
      routine use of the new method and a decreased frequency of stroke may be
      demonstrated.

PMID- 29024266
TI  - Blockable Zn10 L15 Ion Channels through Subcomponent Self-Assembly.
AB  - Metal-organic anion channels based on Zn10 L15 pentagonal prisms have been
      prepared by subcomponent self-assembly. The insertion of these prisms into lipid
      membranes was investigated by ion-current and fluorescence measurements. The
      channels were found to mediate the transport of Cl- anions through planar lipid
      bilayers and into vesicles. Tosylate anions were observed to bind and plug the
      central channels of the prisms in the solid state and in solution. In membranes,
      dodecyl sulfate blocked chloride transport through the central channel. Our Zn10
      L15 prism thus inserts into lipid bilayers to turn on anion transport, which can
      then be turned off through addition of the blocker dodecyl sulfate.

PMID- 29024268
TI  - Perception of Special Needs Dentistry education and practice amongst Australian
      dental auxiliary students.
AB  - INTRODUCTION: The role of dental auxiliaries in collaborative care of patients
      with special needs is compelling. This study was undertaken to investigate the
      perceptions of Special Needs Dentistry (SND) education and practice amongst
      students enrolled in Australian programmes in dental auxiliary, namely dental
      hygiene, dental therapy and oral health therapy (DH/DT/OHT). MATERIALS AND
      METHODS: All Australian institutions offering DH/DT/OHT programmes (n = 14) were
      invited to participate in a self-administered questionnaire survey, conducted
      online, involving students across all academic years. Twelve institutions agreed
      to participate, but only five institutions were included in the final analysis,
      with a student response rate of 31.1%. Answers to open-ended questions were coded
      and grouped for measurement of frequencies. Quantitative data were analysed via
      chi-squared and Fisher's exact tests (significance taken as P < .05). RESULTS:
      The majority of students could not define SND (87.0%) were not aware of the
      existence of this specialty (53.5%) and did not have clinical experience treating
      patients with special needs (68.9%). Nevertheless, they felt comfortable and
      positive about treating these patients independently. Most agreed that they
      should receive clinical and didactic education in SND, with many of them
      expressing interest in pursuing a specialty training in this field. CONCLUSION:
      DH/DT/OHT students' comfort levels, positive attitudes and supportiveness for SND
      suggested positive implications for these practitioners to partake in
      multidisciplinary management of patients with special needs, thus indicating the
      need for standardised training requirements and practice guidelines in this area
      of care.

PMID- 29024267
TI  - Novel T3SS effector EseK in Edwardsiella piscicida is chaperoned by EscH and EscS
      to express virulence.
AB  - Bacterium usually utilises type III secretion systems (T3SS) to deliver effectors
      directly into host cells with the aids of chaperones. Hence, it is very important
      to identify bacterial T3SS effectors and chaperones for better understanding of
      host-pathogen interactions. Edwardsiella piscicida is an invasive enteric
      bacterium, which infects a wide range of hosts from fish to human. Given E.
      piscicida encodes a functional T3SS to promote infection, very few T3SS effectors
      and chaperones have been identified in this bacterium so far. Here, we reported
      that EseK is a new T3SS effector protein translocated by E. piscicida.
      Bioinformatic analysis indicated that escH and escS encode two putative class I
      T3SS chaperones. Further investigation indicated that EscH and EscS can enhance
      the secretion and translocation of EseK. EscH directly binds EseK through
      undetermined binding domains, whereas EscS binds EseK via its N-terminal alpha
      helix. We also found that EseK has an N-terminal chaperone-binding domain, which
      binds EscH and EscS to form a ternary complex. Zebrafish infection experiments
      showed that EseK and its chaperones EscH and EscS are necessary for bacterial
      colonisation in zebrafish. This work identified a new T3SS effector, EseK, and
      its two T3SS chaperones, EscH and EscS, in E. piscicida, which enriches our
      knowledge of bacterial T3SS effector-chaperone interaction and contributes to our
      understanding of bacterial pathogenesis.

PMID- 29024269
TI  - Fluid Resuscitation in Patients With Severe Burns: A Meta-analysis of Randomized
      Controlled Trials.
AB  - OBJECTIVES: Fluid resuscitation is the mainstay treatment to reconstitute
      intravascular volume and maintain end-organ perfusion in patients with severe
      burns. The use of a hyperosmotic or isoosmotic solution in fluid resuscitation to
      manage myocardial depression and increased capillary permeability during burn
      shock has been debated. We conducted a systematic review and meta-analysis to
      compare the efficacies of hyperosmotic and isoosmotic solutions in restoring
      hemodynamic stability after burn injuries. METHODS: PubMed, Embase, Cochrane
      Library, Scopus, and ClinicalTrials.gov registry were searched. Randomized
      control trials evaluating the efficacy and safety of hyperosmotic and isoosmotic
      fluid resuscitation in patients with burn injuries were selected. Eligible trials
      were abstracted and assessed for the risk of bias by two reviewers and results of
      hemodynamic indicators in the included trials were analyzed. RESULTS: Ten trials
      including 502 participants were published between 1983 and 2013. Compared with
      isoosmotic group, the hyperosmotic group exhibited a significant decrease in the
      fluid load (vol/% total body surface area [TBSA]/weight) at 24 hours postinjury,
      with a mean difference of -0.54 (95% confidence interval = -0.92 to -0.17). No
      differences were observed in the urine output, creatinine level, and mortality at
      24 hours postinjury between groups. CONCLUSIONS: Hyperosmotic fluid resuscitation
      appears to be an attractive choice for severe burns in terms of TBSA or burn
      depth. Further investigation is recommended before conclusive recommendation.

PMID- 29024270
TI  - Re: Transverse uterine fundal incision for placenta praevia with accreta,
      involving the entire anterior uterine wall: a case series. Spontaneous uterine
      rupture during the subsequent pregnancy after transverse uterine fundal incision
      for placenta praevia with accreta.

PMID- 29024271
TI  - Impact of the Long-Range Electronic Effect of a Fluorous Ponytail on Metal
      Coordination during Solvent Extraction.
AB  - With the need for a precise description of the long-range electronic effects of a
      perfloroalkyl chain (F-ponytail) grafted onto metal chelators, we studied in
      detail the effect of a spacer inserted between the polar complexing head and the
      F-ponytail, in relation to the metal coordination ability of the resulting
      molecules. The prepared molecules were then applied for the extraction of various
      metals from an aqueous phase into an organic phase, and the optimum spacer length
      could be estimated to be between three and four methylene units, according to the
      extraction conditions. The study also revealed the difficulty of modeling and
      anticipating the tiny energy differences involved in the extraction process and
      the importance in peculiar cases to go beyond only these studied inductive
      effects to understand better the factors that govern the stabilization of a
      metallic cation in a complex fluorous phase.

PMID- 29024272
TI  - Ligand- and Solvent-Controlled Regio- and Chemodivergent Carbonylative Reactions.
AB  - The development of highly selective procedures is one of the core goals in
      organic chemistry. Among the known organic transformations, carbonylation
      reactions present an ideal choice for the preparation of carbonyl-containing
      compounds. In this review, the recent achievements on the control of the
      selectivity for carbonylation reactions have been summarized. The effects of
      ligands, solvents, and bases on the selectivity are been discussed.

PMID- 29024273
TI  - The first brain: Species comparisons and evolutionary implications for the
      enteric and central nervous systems.
AB  - BACKGROUND: The enteric nervous system (ENS) and the central nervous system (CNS)
      of mammals both contain integrative neural circuitry and similarities between
      them have led to the ENS being described as the brain in the gut. PURPOSE: To
      explore relationships between the ENS and CNS across the animal kingdom. We found
      that an ENS occurs in all animals investigated, including hydra, echinoderms and
      hemichordates that do not have a CNS. The general form of the ENS, which consists
      of plexuses of neurons intrinsic to the gut wall and an innervation that controls
      muscle movements, is similar in species as varied and as far apart as hydra, sea
      cucumbers, annelid worms, octopus and humans. Moreover, neurochemical
      similarities across phyla imply a common origin of the ENS. Investigation of
      extant species suggests that the ENS developed in animals that preceded the
      division that led to cnidaria (exemplified by hydra) and bilateria, which
      includes the vertebrates. The CNS is deduced to be a bilaterian development,
      later than the divergence from cnidaria. Consistent with the ENS having developed
      independent of the CNS, reciprocal connections between ENS and CNS occur in
      mammals, and separate neurons of ENS and CNS origin converge on visceral organs
      and prevertebral ganglia. We conclude that an ENS arose before and independently
      of the CNS. Thus the ENS can be regarded as the first brain.

PMID- 29024274
TI  - Second-generation drug-eluting stents versus drug-coated balloons for the
      treatment of coronary in-stent restenosis: A systematic review and meta-analysis.
AB  - PURPOSE: The benefit of drug-eluting stents (DES) versus drug-coated balloons
      (DCB) in coronary artery in-stent restenosis (ISR) for the prevention of target
      lesion revascularization (TLR), stent thrombosis, and mortality remains
      uncertain. Our aim was to synthesize the available evidence from randomized
      clinical trials (RCTs) and observational studies that directly compare second
      generation drug-eluting stents (SG-DES) and DCB for the treatment of coronary
      ISR. METHODS: Medline, Embase, and Cochrane Central were searched for RCTs or
      observational studies, published up to March 15, 2017. A random effects model
      meta-analysis investigating clinical and angiographic outcomes was conducted for
      RCTs and observational studies that compared SG-DES versus DCB for the treatment
      of ISR. RESULTS: Ten studies and 2,173 patients were included in this meta
      analysis. The two treatment strategies were proven equal with regards to TLR,
      myocardial infarction, stent thrombosis, and cardiac mortality in both randomized
      and observational studies. No difference was found among RCTs for all-cause
      mortality, while in observational studies, patients who were treated with SG-DES
      had a lower mortality compared to DCB (OR: 0.47; 95% CI: 0.27-0.83). In the
      pooled analysis also (RCTs and observational studies), SG-DES were associated
      with lower all-cause mortality compared to DCB. Patients treated with SG-DES were
      also superior in terms of minimal lumen diameter (standardized mean difference:
      0.39; 95% CI: 0.12-0.66). CONCLUSIONS: The two treatment strategies are equal for
      the treatment of ISR, while the difference in all-cause mortality might be
      potentially explained by baseline differences in the two groups among real-world
      studies.

PMID- 29024275
TI  - The Structure of Diphenyl Ether-Methanol in the Electronically Excited and Ionic
      Ground States: A Combined IR/UV Spectroscopic and Theoretical Study.
AB  - Diphenyl ether offers competing docking sites for methanol: the ether oxygen acts
      as a common hydrogen-bond acceptor and the pi system of each phenyl ring allows
      for OH-pi interactions driven by electrostatic, induction, and dispersion forces.
      Based on investigations in the electronic ground state (S0 ), we present a
      detailed study of the electronically excited state (S1 ) and the ionic ground
      state (D0 ), in which an impact on the structural preference is expected compared
      with the S0 state. Dispersion forces in the electronically excited state were
      analyzed by comparing the computed binding energies at the coupled-cluster
      singles (CCS) and approximate coupled-cluster-singles-doubles levels of theory
      (CC2 approximation). By applying UV/IR/UV spectroscopy, we found a more strongly
      bound OH-pi structure in the S1 state compared with the S0 state, in agreement
      with spin-component-scaled CC2 calculations. A structural rearrangement into a
      non-hydrogen-bonded structure takes places upon ionization in the D0 state, which
      was revealed by using IR photodissociation spectroscopy and confirmed by theory.

PMID- 29024276
TI  - Large plaque-type blue naevus with cellular nodules: a rare unrecognized
      melanocytic tumour.

PMID- 29024277
TI  - How intraspecific variation in seed-dispersing animals matters for plants.
AB  - Seed dispersal by animals is a complex phenomenon, characterized by multiple
      mechanisms and variable outcomes. Most researchers approach this complexity by
      analysing context-dependency in seed dispersal and investigating extrinsic
      factors that might influence interactions between plants and seed dispersers.
      Intrinsic traits of seed dispersers provide an alternative way of making sense of
      the enormous variation in seed fates. I review causes of intraspecific
      variability in frugivorous and granivorous animals, discuss their effects on seed
      dispersal, and outline likely consequences for plant populations and communities.
      Sources of individual variation in seed-dispersing animals include sexual
      dimorphism, changes associated with growth and ageing, individual specialization,
      and animal personalities. Sexual dimorphism of seed-dispersing animals influences
      seed fate through diverse mechanisms that range from effects caused by sex
      specific differences in body size, to influences of male versus female cognitive
      functions. These differences affect the type of seed treatment (e.g. dispersal
      versus predation), the number of dispersed seeds, distance of seed dispersal, and
      likelihood that seeds are left in favourable sites for seeds or seedlings. The
      best-documented consequences of individual differences associated with growth and
      ageing involve quantity of dispersed seeds and the quality of seed treatment in
      the mouth and gut. Individual specialization on different resources affects the
      number of dispersed plant species, and therefore the connectivity and
      architecture of seed-dispersal networks. Animal personalities might play an
      important role in shaping interactions between plants and dispersers of their
      seeds, yet their potential in this regard remains overlooked. In general,
      intraspecific variation in seed-dispersing animals often influences plants
      through effects of these individual differences on the movement ecology of the
      dispersers. Two conditions are necessary for individual variation to exert a
      strong influence on seed dispersal. First, the individual differences in traits
      should translate into differences in crucial characteristics of seed dispersal.
      Second, individual variation is more likely to be important when the proportions
      of particular types of individuals fluctuate strongly in a population or vary
      across space; when proportions are static, it is less likely that intraspecific
      differences will be responsible for changes in the dynamics and outcomes of plant
      animal interactions. In conclusion, focusing on variation among foraging animals
      rather than on species averages might bring new, mechanistic insights to the
      phenomenon of seed dispersal. While this shift in perspective is unlikely to
      replace the traditional approach (based on the assumption that all important
      variation occurs among species), it provides a complementary alternative to
      decipher the enormous variation observed in animal-mediated seed dispersal.

PMID- 29024278
TI  - Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential
      volume regulation hypothesis.
AB  - The effect of a sodium glucose cotransporter 2 inhibitor (SGLT2i) in reducing
      heart failure hospitalization in the EMPA-REG OUTCOMES trial has raised the
      possibility of using these agents to treat established heart failure. We
      hypothesize that osmotic diuresis induced by SGLT2 inhibition, a distinctly
      different diuretic mechanism than that of other diuretic classes, results in
      greater electrolyte-free water clearance and, ultimately, in greater fluid
      clearance from the interstitial fluid (IF) space than from the circulation,
      potentially resulting in congestion relief with minimal impact on blood volume,
      arterial filling and organ perfusion. We utilize a mathematical model to
      illustrate that electrolyte-free water clearance results in a greater reduction
      in IF volume compared to blood volume, and that this difference may be mediated
      by peripheral sequestration of osmotically inactive sodium. By coupling the model
      with data on plasma and urinary sodium and water in healthy subjects who received
      either the SGLT2i dapagliflozin or loop diuretic bumetanide, we predict that
      dapagliflozin produces a 2-fold greater reduction in IF volume compared to blood
      volume, while the reduction in IF volume with bumetanide is only 78% of the
      reduction in blood volume. Heart failure is characterized by excess fluid
      accumulation, in both the vascular compartment and interstitial space, yet many
      heart failure patients have arterial underfilling because of low cardiac output,
      which may be aggravated by conventional diuretic treatment. Thus, we hypothesize
      that, by reducing IF volume to a greater extent than blood volume, SGLT2
      inhibitors might provide better control of congestion without reducing arterial
      filling and perfusion.

PMID- 29024279
TI  - Computed tomographic-lymphography as a complementary technique for lymph node
      staging in dogs with malignant tumors of various sites.
AB  - Locoregional lymph nodes are routinely examined in order to define the spatial
      extent of neoplastic disease. As draining patterns of certain tumor types can be
      divergent from expected anatomical distribution, it is critical to sample the
      lymph nodes truly representing the draining area. The aim of this bicenter
      prospective pilot study was to describe the technique of computed tomographic
      (CT)-lymphography for primary draining lymph node mapping in tumor staging in
      dogs. Forty-five dogs with macro- or microscopic tumors in specified
      localizations were evaluated. Depending on body weight, 0.8-2 ml contrast agent
      (iohexol) was injected into four quadrants around the tumor, and CT-images were
      obtained at 1, 3, 6, 9, and 12 minutes post-injection. Attenuation of chosen
      regions of interest (Hounsfield units (HU)) and patterns of enhancement were
      assessed for 284 lymph nodes in the precontrast study with median HUs of 31.1
      (Interquartile range (IQR) = 18.4) and for 275 in the intravenous postcontrast
      study with 104.3 HU (IQR = 31.2) (paired Wilcoxon test, P < 0.001). In the CT
      lymphography study, 45 primary draining lymph nodes with a significantly higher
      median HU value of 348.5 (IQR = 591.4) (one-sample t-test, P < 0.001) were
      identified. Primary draining lymph nodes were found to be clearly visible after 1
      3 minutes after local injection, often concurrent with a good visibility of the
      lymphatic vessel system. The herein described technique of peritumorally injected
      CT-contrast agent followed by subsequent CT-lymphography for primary draining
      lymph node mapping works well in a majority of cases in all investigated sites
      and warrants further validation for different tumor entities.

PMID- 29024280
TI  - Laparoscopic pancreaticoduodenectomy in Brisbane, Australia: an initial
      experience.
AB  - BACKGROUND: The role of minimally invasive approach for pancreaticoduodenectomy
      has not yet been well defined in Australia. We present our early experience with
      laparoscopic pancreaticoduodenectomy (LPD) from Brisbane, Australia. METHODS:
      Retrospective review in a prospectively collected database of patients undergoing
      LPD between 2006 and 2016 was performed. Patients who underwent a hybrid LPD
      (HLPD) mobilization approach and resection followed by open reconstruction and
      totally LPD (TLPD) approach were included in this study. Operative
      characteristics, perioperative outcomes, pathological and survival data were
      collected. RESULTS: Twenty-seven patients underwent LPD including 17 HLPD (63%)
      and 10 TLPD (37%) patients. HLPD patients were mostly converted to open for
      planned reconstruction or vascular resection. With increasing experience, more
      TLPDs were performed, including laparoscopic anastomoses. Median operating time
      was 462 min (504 min for TLPD). Median length of hospital stay was 10 days.
      Histology showed 21 invasive malignancies, two neuroendocrine tumours, two
      intraductal papillary mucinous neoplasms and two benign lesions. Median nodal
      harvest was 22. Margin negative resection was achieved in 84% of patients. Twenty
      two percent of patients developed a Grade 3/4 complication, including 19%
      clinically significant pancreatic fistula. There was one perioperative mortality
      (4%) due to pancreatic fistula, post-operative haemorrhage and sepsis.
      CONCLUSIONS: LPD is a technically challenging operation with a steep learning
      curve. The early oncological outcomes appear satisfactory. It remains to be
      determined whether the minimally invasive approach to pancreaticoduodenectomy
      offers benefits to patients.

PMID- 29024281
TI  - Development of a Sensitive Microarray Platform for the Ranking of Galectin
      Inhibitors: Identification of a Selective Galectin-3 Inhibitor.
AB  - Glycan microarrays are useful tools for lectin glycan profiling. The use of a
      glycan microarray based on evanescent-field fluorescence detection was herein
      further extended to the screening of lectin inhibitors in competitive
      experiments. The efficacy of this approach was tested with 2/3'-mono- and 2,3'
      diaromatic type II lactosamine derivatives and galectins as targets and was
      validated by comparison with fluorescence anisotropy proposed as an orthogonal
      protein interaction measurement technique. We showed that subtle differences in
      the architecture of the inhibitor could be sensed that pointed out the preference
      of galectin-3 for 2'-arylamido derivatives over ureas, thioureas, and amines and
      that of galectin-7 for derivatives bearing an alpha substituent at the anomeric
      position of glucosamine. We eventually identified a diaromatic oxazoline as a
      highly specific inhibitor of galectin-3 versus galectin-1 and galectin-7.

PMID- 29024282
TI  - Anion Relay Chemistry: Development of an Effective Diastereoselective [3+2]
      Annulation Tactic Exploiting an Aldol/Brook Rearrangement/Cyclization Cascade.
AB  - An effective [3+2] annulation tactic for the construction of diverse bicyclic
      compounds possessing highly functionalized cyclopentane rings has been developed
      employing soft ketone enolates as the initial nucleophile for anion relay
      chemistry (ARC). The protocol entails a highly diastereoselective aldol/Brook
      rearrangement/cyclization cascade.

PMID- 29024283
TI  - Mechanisms of human cytomegalovirus infection with a focus on epidermal growth
      factor receptor interactions.
AB  - Human cytomegalovirus (HCMV) is a widespread opportunistic herpesvirus that
      causes severe diseases in immunocompromised individuals. It has a high prevalence
      worldwide that is linked with socioeconomic factors. Similar to other
      herpesviruses, HCMV has the ability to establish lifelong persistence and latent
      infection following primary exposure. HCMV infects a broad range of cell types.
      This broad tropism suggests that it may use multiple receptors for host cell
      entry. The identification of receptors used by HCMV is essential for
      understanding viral pathogenesis, because these receptors mediate the early
      events necessary for infection. Many cell surface components have been identified
      as virus receptors, such as epidermal growth factor receptor (EGFR), which is
      characterized by tyrosine kinase activity and plays a crucial role in the control
      of key cellular transduction pathways. EGFR is essential for HCMV binding,
      signaling, and host cell entry. This review focuses on HCMV infection via EGFR on
      different cell types and its implications for the cellular environment, viral
      persistence, and infection.

PMID- 29024284
TI  - How do people with long-term mental health problems negotiate relationships with
      network members at times of crisis?
AB  - BACKGROUND: Social network processes impact on the genesis and management of
      mental health problems. There is currently less understanding of the way people
      negotiate networked relationships in times of crisis compared to how they manage
      at other times. OBJECTIVE: This paper explores the patterns and nature of
      personal network involvement at times of crises and how these may differ from day
      to-day networks of recovery and maintenance. METHOD: Semi-structured interviews
      with 25 participants with a diagnosis of long-term mental health (MH) problems
      drawn from recovery settings in the south of England. Interviews centred on
      personal network mapping of members and resources providing support. The mapping
      interviews explored the work of network members and changes in times of crisis.
      Interviews were recorded, transcribed and analysed using a framework analysis.
      RESULTS: Three key themes were identified: the fluidity of network relationality
      between crisis and recovery; isolation as a means of crises management; leaning
      towards peer support. Personal network input retreated at times of crisis often
      as result of "ejection" from the network by participants who used self-isolation
      as a personal management strategy in an attempt to deal with crises. Peer support
      is considered useful during a crisis, whilst the role of services was viewed with
      some ambiguity. CONCLUSIONS: Social networks membership, and type and depth of
      involvement, is subject to change between times of crisis and everyday support.
      This has implications for managing mental health in terms of engaging with
      network support differently in times of crises versus recovery and everyday
      living.

PMID- 29024285
TI  - Effect of a high-cholesterol diet on lipoprotein metabolism and xanthoma
      formation in rabbits.
AB  - BACKGROUND: Xanthelasma is the most common type of cutaneous xanthoma and often
      occurs on the eyelids. Xanthoma has been reported to be highly correlated with
      abnormal lipoprotein metabolism. AIMS: In this study, we wanted to investigate
      the effects of a high-cholesterol diet on xanthoma formation and lipoprotein
      metabolism in rabbits. METHODS: In animals fed with high-cholesterol diet,
      deteced plasma lipid [ie, total cholesterol (TC), triglycerides (TG), and low
      density lipoprotein cholesterol (L-DLC)] levels and pathology of xanthoma.
      RESULTS: Plasma lipid levels were dramatically elevated within 8 weeks. In
      addition, high dietary cholesterol promoted xanthoma formation on the napex.
      Microscopic examination showed that foam cells laden with cholesterol deposits
      accumulated around the dermal capillaries and cutaneous appendages within the
      skin of the napex. CONCLUSION: These findings indicate a critical role for a high
      cholesterol diet in the dysregulation of lipoprotein metabolism and the
      development of xanthoma in rabbits. The results suggest that abnormal lipid
      metabolism may increase the occurrence of xanthoma.

PMID- 29024286
TI  - Modelling cumulative exposure for inference about drug effects in observational
      studies.
AB  - PURPOSE: To demonstrate a modelling approach that controls for time-invariant
      allocation bias in estimation of associations of outcome with drug exposure.
      METHODS: We show that in a model that includes terms for both ever-exposure
      versus never-exposure and cumulative exposure, the parameter for ever-exposure
      represents the effect of time-invariant allocation bias, and the parameter for
      cumulative exposure represents the effect of the drug after adjustment for this
      unmeasured confounding. This assumes no stepwise effect of the drug on the event
      rate, no reverse causation, and no unmeasured time-varying confounders. We
      demonstrated this by modelling the effect of statins on cardiovascular disease,
      for which the true effect has been well characterised in randomised trials, using
      time-updated Cox regression models in a national cohort of Type 2 diabetes
      patients. RESULTS: The crude hazard ratio associated with ever-use of statins was
      1.13 in a standard cohort analysis comparing exposed with unexposed person-time
      intervals. When ever-never use and cumulative exposure are modelled jointly, the
      effect of statins can be estimated from the cumulative exposure parameter (hazard
      ratio 0.97 per year of exposure, 95% CI 0.97 to 0.98). The ever-exposed term
      (hazard ratio 1.20, 1.16 to 1.23) in this model can be interpreted as estimating
      the allocation bias. CONCLUSIONS: Where stepwise effects on the risk of adverse
      events are unlikely, as for instance for effects on risk of cancer, joint
      modelling of ever-never and cumulative exposure can be used to study the effects
      of multiple drugs and to distinguish causal effects from confounding by
      allocation.

PMID- 29024287
TI  - Inflammation and cardio-renal interactions in heart failure: a potential role for
      interleukin-6.

PMID- 29024288
TI  - High-resolution mapping of the pericentromeric region on wheat chromosome arm 5AS
      harbouring the Fusarium head blight resistance QTL Qfhs.ifa-5A.
AB  - The Qfhs.ifa-5A allele, contributing to enhanced Fusarium head blight resistance
      in wheat, resides in a low-recombinogenic region of chromosome 5A close to the
      centromere. A near-isogenic RIL population segregating for the Qfhs.ifa-5A
      resistance allele was developed and among 3650 lines as few as four recombined
      within the pericentromeric C-5AS1-0.40 bin, yielding only a single recombination
      point. Genetic mapping of the pericentromeric region using a recombination
      dependent approach was thus not successful. To facilitate fine-mapping the
      physically large Qfhs.ifa-5A interval, two gamma-irradiated deletion panels were
      generated: (i) seeds of line NIL3 carrying the Qfhs.ifa-5A resistance allele in
      an otherwise susceptible background were irradiated and plants thereof were
      selfed to obtain deletions in homozygous state and (ii) a radiation hybrid panel
      was produced using irradiated pollen of the wheat line Chinese Spring (CS) for
      pollinating the CS-nullisomic5Atetrasomic5B. In total, 5157 radiation selfing and
      276 radiation hybrid plants were screened for deletions on 5AS and plants
      containing deletions were analysed using 102 5AS-specific markers. Combining
      genotypic information of both panels yielded an 817-fold map improvement (cR/cM)
      for the centromeric bin and was 389-fold increased across the Qfhs.ifa-5A
      interval compared to the genetic map, with an average map resolution of 0.77
      Mb/cR. We successfully proved that the RH mapping technique can effectively
      resolve marker order in low-recombining regions, including pericentromeric
      intervals, and simultaneously allow developing an in vivo panel of sister lines
      differing for induced deletions across the Qfhs.ifa-5A interval that can be used
      for phenotyping.

PMID- 29024289
TI  - Diastereoselective C-H Bond Amination for Disubstituted Pyrrolidines.
AB  - We report herein the improved diastereoselective synthesis of 2,5-disubstituted
      pyrrolidines from aliphatic azides. Experimental and theoretical studies of the C
      H amination reaction mediated by the iron dipyrrinato complex (Ad L)FeCl(OEt2 )
      provided a model for diastereoinduction and allowed for systematic variation of
      the catalyst to enhance selectivity. Among the iron alkoxide and aryloxide
      catalysts evaluated, the iron phenoxide complex exhibited superior performance
      towards the generation of syn 2,5-disubstituted pyrrolidines with high
      diastereoselectivity.

PMID- 29024290
TI  - Novel bisthioether derivatives containing a 1,3,4-oxadiazole moiety: design,
      synthesis, antibacterial and nematocidal activities.
AB  - BACKGROUND: The literature shows that bisthioether and 1,3,4-oxadiazole
      derivatives exhibit a wide variety of biological activities. In this study, a
      series of novel bisthioether derivatives containing a 1,3,4-oxadiazole moiety
      were synthesized and their antibacterial and nematocidal activities investigated.
      RESULTS: Among the title compounds evaluated, compound 4f demonstrated the best
      antibacterial activities against rice bacterial leaf blight, rice bacterial leaf
      streak and citrus canker caused by Xanthomonas oryzae pv. oryzae (Xoo),
      Xanthomonas oryzae pv. oryzicola (Xoc) and Xanthomonas axonopodis pv. citri
      (Xac), with EC50 values of 4.82, 11.15 and 16.57 ug mL-1 , respectively, which
      were even better than those of thiodiazole copper and bismerthiazol. Meanwhile,
      compound 4f had better in vitro nematocidal activity against Caenorhabditis
      elegans at 48 h, with an LC50 value of 2.89 ug mL-1 , which was superior to those
      of ethoprophos and fosthiazate. In addition, greenhouse trials indicated that
      compound 4f was effective in reducing rice bacterial leaf blight relative to
      thiodiazole copper and bismerthiazol. CONCLUSION: A series of novel bisthioether
      derivatives containing a 1,3,4-oxadiazole moiety were synthesized and bioassay
      results showed that compound 4f exhibited the best antibacterial and nematocidal
      activities. (c) 2017 Society of Chemical Industry.

PMID- 29024292
TI  - Hepatic cystic echinococcosis in Australia: an update on diagnosis and
      management.
AB  - BACKGROUND: Echinococcosis is an uncommonly encountered zoonotic disease caused
      by the taeniid Echinococcus. The only endemic species in Australia, Echinococcus
      granulosus, forms cysts in the liver in 70% of cases. The aim of this study was
      to review the literature to provide an evidence-based narrative update on the
      diagnosis and management of hepatic cystic echinococcosis in Australia. METHODS:
      We reviewed the literature, utilizing multiple research databases and citation
      tracking. Original research and review articles examining the diagnosis and
      management of hydatid disease in adults, published prior to 2016 and in the
      English language were included in our review. RESULTS: Ultrasound is the gold
      standard screening test, whilst computed tomography has a role in emergency
      presentations and screening for multi-organ involvement. Magnetic resonance
      imaging is the preferred second-line imaging and better demonstrates biliary
      involvement. Medical therapy or PAIR (percutaneous aspiration, irrigation with
      scolicide and re-aspiration) may be appropriate in selected cases; however,
      surgery remains the definitive treatment for active, large (>5 cm), symptomatic
      or complicated cysts. A variety of surgical techniques have been described,
      including conservative, radical and minimally invasive procedures. There is
      currently no consensus approach; surgical modality should be tailored to patient
      factors, relevant anatomy, local facilities and surgeons' expertise. CONCLUSION:
      Diagnosis and therapy in hepatic hydatid cysts have been significantly advanced
      by imaging, interventional radiology and surgical approaches in recent years.
      Surgery remains the mainstay of treatment for large, active, complicated or
      symptomatic hepatic hydatid cysts.

PMID- 29024291
TI  - Phosphorylation coexists with O-GlcNAcylation in a plant virus protein and
      influences viral infection.
AB  - Phosphorylation and O-GlcNAcylation are two widespread post-translational
      modifications (PTMs), often affecting the same eukaryotic target protein. Plum
      pox virus (PPV) is a member of the genus Potyvirus which infects a wide range of
      plant species. O-GlcNAcylation of the capsid protein (CP) of PPV has been studied
      extensively, and some evidence of CP phosphorylation has also been reported.
      Here, we use proteomics analyses to demonstrate that PPV CP is phosphorylated in
      vivo at the N-terminus and the beginning of the core region. In contrast with the
      'yin-yang' mechanism that applies to some mammalian proteins, PPV CP
      phosphorylation affects residues different from those that are O-GlcNAcylated
      (serines Ser-25, Ser-81, Ser-101 and Ser-118). Our findings show that PPV CP can
      be concurrently phosphorylated and O-GlcNAcylated at nearby residues. However, an
      analysis using a differential proteomics strategy based on iTRAQ (isobaric tags
      for relative and absolute quantitation) showed a significant enhancement of
      phosphorylation at Ser-25 in virions recovered from O-GlcNAcylation-deficient
      plants, suggesting that crosstalk between O-GlcNAcylation and phosphorylation in
      PPV CP takes place. Although the preclusion of phosphorylation at the four
      identified phosphotarget sites only had a limited impact on viral infection, the
      mimicking of phosphorylation prevents PPV infection in Prunus persica and weakens
      infection in Nicotiana benthamiana and other herbaceous hosts, prompting the
      emergence of potentially compensatory second mutations. We postulate that the
      joint action of phosphorylation and O-GlcNAcylation in the N-proximal segment of
      CP allows a fine-tuning of protein stability, providing the amount of CP required
      in each step of viral infection.

PMID- 29024295
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 43/2017.

PMID- 29024293
TI  - 3D Porous Hydrogel/Conducting Polymer Heterogeneous Membranes with Electro-/pH
      Modulated Ionic Rectification.
AB  - Heterogeneous membranes composed of asymmetric structures or compositions have
      enormous potential in sensors, molecular sieves, and energy devices due to their
      unique ion transport properties such as ionic current rectification and ion
      selectivity. So far, heterogeneous membranes with 1D nanopores have been
      extensively studied. However, asymmetric structures with 3D micro-/nanoscale pore
      networks have never been investigated. Here, a simple and versatile approach to
      low-costly fabricate hydrogel/conducting polymer asymmetric heterogeneous
      membranes with electro-/pH-responsive 3D micro-/nanoscale ion channels is
      introduced. Due to the asymmetric heterojunctions between positively charged
      nanoporous polypyrrole (PPy) and negatively charged microscale porous hydrogel
      poly (acrylamide-co-acrylic acid) (P(AAm-co-AA)), the membrane can rectify ion
      transmembrane transport in response to both electro- and pH-stimuli. Numerical
      simulations based on coupled Poisson and Nernst-Plank equations are carried out
      to explain the ionic rectification mechanisms for the membranes. The membranes
      are not dependent on elaborately fabricated 1D ion channel substrates and hence
      can be facilely prepared in a low-cost and large-area way. The hybridization of
      hydrogel and conducting polymer offers a novel strategy for constructing low
      cost, large-area and multifunctional membranes, expanding the tunable ionic
      rectification properties into macroscopic membranes with micro-/nanoscale pores,
      which would stimulate practical applications of the membranes.

PMID- 29024294
TI  - Cognitive, motor, behavioural and academic performances of children born preterm:
      a meta-analysis and systematic review involving 64 061 children.
AB  - BACKGROUND: Preterm birth may leave the brain vulnerable to dysfunction.
      Knowledge of future neurodevelopmental delay in children born with various
      degrees of prematurity is needed to inform practice and policy. OBJECTIVE: To
      quantify the long-term cognitive, motor, behavioural and academic performance of
      children born with different degrees of prematurity compared with term-born
      children. SEARCH STRATEGY: PubMed and Embase were searched from January 1980 to
      December 2016 without language restrictions. SELECTION CRITERIA: Observational
      studies that reported neurodevelopmental outcomes from 2 years of age in children
      born preterm compared with a term-born cohort. DATA COLLECTION AND ANALYSIS: We
      pooled individual estimates of standardised mean differences (SMD) and odds
      ratios (OR) with 95% confidence intervals using a random effects model. MAIN
      RESULTS: We included 74 studies (64 061 children). Preterm children had lower
      cognitive scores for FSIQ (SMD: -0.70; 95% CI: -0.73 to -0.66), PIQ (SMD: -0.67;
      95% CI: -0.73 to -0.60) and VIQ (SMD: -0.53; 95% CI: -0.60 to -0.47). Lower
      scores for preterm children in motor skills, behaviour, reading, mathematics and
      spelling were observed at primary school age, and this persisted to secondary
      school age, except for mathematics. Gestational age at birth accounted for 38-48%
      of the observed IQ variance. ADHD was diagnosed twice as often in preterm
      children (OR: 1.6; 95% CI: 1.3-1.8), with a differential effect observed
      according to the severity of prematurity (I2 = 49.4%, P = 0.03). CONCLUSIONS:
      Prematurity of any degree affects the cognitive performance of children born
      preterm. The poor neurodevelopment persists at various ages of follow up.
      Parents, educators, healthcare professionals and policy makers need to take into
      account the additional academic, emotional and behavioural needs of these
      children. TWEETABLE ABSTRACT: Adverse effect of preterm birth on a child's
      neurodevelopment persists up to adulthood.

PMID- 29024296
TI  - Evolving Accelerated Amidation by SpyTag/SpyCatcher to Analyze Membrane Dynamics.
AB  - SpyTag is a peptide that forms a spontaneous amide bond with its protein partner
      SpyCatcher. This protein superglue is a broadly useful tool for molecular
      assembly, locking together biological building blocks efficiently and
      irreversibly in diverse architectures. We initially developed SpyTag and
      SpyCatcher by rational design, through splitting a domain from a Gram-positive
      bacterial adhesin. In this work, we established a phage-display platform to
      select for specific amidation, leading to an order of magnitude acceleration for
      interaction of the SpyTag002 variant with the SpyCatcher002 variant. We show that
      the 002 pair bonds rapidly under a wide range of conditions and at either protein
      terminus. SpyCatcher002 was fused to an intimin derived from enterohemorrhagic
      Escherichia coli. SpyTag002 reaction enabled specific and covalent decoration of
      intimin for live cell fluorescent imaging of the dynamics of the bacterial outer
      membrane as cells divide.

PMID- 29024298
TI  - Detailed Evidence for an Unparalleled Interaction Mode between Calmodulin and
      Orai Proteins.
AB  - Calmodulin (CaM) binds most of its targets by wrapping around an amphipathic
      alpha-helix. The N-terminus of Orai proteins contains a conserved CaM-binding
      segment but the binding mechanism has been only partially characterized. Here,
      microscale thermophoresis (MST), surface plasmon resonance (SPR), and atomic
      force microscopy (AFM) were employed to study the binding equilibria, the
      kinetics, and the single-molecule interaction forces involved in the binding of
      CaM to the conserved helical segments of Orai1 and Orai3. The results
      consistently indicated stepwise binding of two separate target peptides to the
      two lobes of CaM. An unparalleled high affinity was found when two Orai peptides
      were dimerized or immobilized at high lateral density, thereby mimicking the
      close proximity of the N-termini in native Orai oligomers. The analogous
      experiments with smooth muscle myosin light chain kinase (smMLCK) showed only the
      expected 1:1 binding, confirming the validity of our methods.

PMID- 29024297
TI  - Reducing dose to the lungs through loosing target dose homogeneity requirement
      for radiotherapy of non small cell lung cancer.
AB  - It is important to minimize lung dose during intensity-modulated radiation
      therapy (IMRT) of nonsmall cell lung cancer (NSCLC). In this study, an approach
      was proposed to reduce lung dose by relaxing the constraint of target dose
      homogeneity during treatment planning of IMRT. Ten NSCLC patients with lung tumor
      on the right side were selected. The total dose for planning target volume (PTV)
      was 60 Gy (2 Gy/fraction). For each patient, two IMRT plans with six beams were
      created in Pinnacle treatment planning system. The dose homogeneity of target was
      controlled by constraints on the maximum and uniform doses of target volume. One
      IMRT plan was made with homogeneous target dose (the resulting target dose was
      within 95%-107% of the prescribed dose), while another IMRT plan was made with
      inhomogeneous target dose (the resulting target dose was more than 95% of the
      prescribed dose). During plan optimization, the dose of cord and heart in two
      types of IMRT plans were kept nearly the same. The doses of lungs, PTV and organs
      at risk (OARs) between two types of IMRT plans were compared and analyzed
      quantitatively. For all patients, the lung dose was decreased in the IMRT plans
      with inhomogeneous target dose. On average, the mean dose, V5, V20, and V30 of
      lung were reduced by 1.4 Gy, 4.8%, 3.7%, and 1.7%, respectively, and the dose to
      normal tissue was also reduced. These reductions in DVH values were all
      statistically significant (P < 0.05). There were no significant differences
      between the two IMRT plans on V25, V30, V40, V50 and mean dose for heart. The
      maximum doses of cords in two type IMRT plans were nearly the same. IMRT plans
      with inhomogeneous target dose could protect lungs better and may be considered
      as a choice for treating NSCLC.

PMID- 29024299
TI  - Reproducibility of R-fMRI metrics on the impact of different strategies for
      multiple comparison correction and sample sizes.
AB  - Concerns regarding reproducibility of resting-state functional magnetic resonance
      imaging (R-fMRI) findings have been raised. Little is known about how to
      operationally define R-fMRI reproducibility and to what extent it is affected by
      multiple comparison correction strategies and sample size. We comprehensively
      assessed two aspects of reproducibility, test-retest reliability and
      replicability, on widely used R-fMRI metrics in both between-subject contrasts of
      sex differences and within-subject comparisons of eyes-open and eyes-closed
      (EOEC) conditions. We noted permutation test with Threshold-Free Cluster
      Enhancement (TFCE), a strict multiple comparison correction strategy, reached the
      best balance between family-wise error rate (under 5%) and test-retest
      reliability/replicability (e.g., 0.68 for test-retest reliability and 0.25 for
      replicability of amplitude of low-frequency fluctuations (ALFF) for between
      subject sex differences, 0.49 for replicability of ALFF for within-subject EOEC
      differences). Although R-fMRI indices attained moderate reliabilities, they
      replicated poorly in distinct datasets (replicability < 0.3 for between-subject
      sex differences, < 0.5 for within-subject EOEC differences). By randomly drawing
      different sample sizes from a single site, we found reliability, sensitivity and
      positive predictive value (PPV) rose as sample size increased. Small sample sizes
      (e.g., < 80 [40 per group]) not only minimized power (sensitivity < 2%), but also
      decreased the likelihood that significant results reflect "true" effects (PPV <
      0.26) in sex differences. Our findings have implications for how to select
      multiple comparison correction strategies and highlight the importance of
      sufficiently large sample sizes in R-fMRI studies to enhance reproducibility. Hum
      Brain Mapp 39:300-318, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29024301
TI  - Concise Review: Emerging Principles from the Clinical Application of Chimeric
      Antigen Receptor T Cell Therapies for B Cell Malignancies.
AB  - Gene-engineered T cell therapies are soon to be United States Food and Drug
      Administration (FDA) approved for at least two types of B cell malignancies in
      pediatric and adult patients, in the form of CD19 targeted chimeric antigen
      receptor T (CAR T) cell therapy. This represents a triumph of a true bench to
      bedside clinical translation of a therapy that was conceived of in the early
      1990s. Clinical results have demonstrated efficacious responses in patients with
      the CD19 positive diseases B cell acute lymphoblastic leukemia and diffuse large
      B cell lymphoma. However, significant challenges have emerged, including
      worrisome immune-related toxicities, therapy resistance, and understanding how to
      administer CD19 CAR T cells in clinical practice. Although much remains to be
      learned, pioneering clinical trials have led to foundational insights about the
      clinical translation of this novel therapy. Here, we review the "lessons learned"
      from the pre-clinical and human experience with CAR T cell therapy. Stem Cells
      2018;36:36-44.

PMID- 29024303
TI  - The influence of crown-to-implant ratio on marginal bone levels around splinted
      short dental implants: A radiological and clincial short term analysis.
AB  - BACKGROUND: The amount of marginal bone resorption around dental implants is
      considered to have a significant impact on implant stability as well as implant
      survival rates. PURPOSE: The aim of this prospective study was to investigate the
      influence of prosthetic as well as patient specific factors on marginal bone loss
      around short dental implants. MATERIALS AND METHODS: Seventy-six implants, which
      supported splinted crowns were included for investigation. All implants were from
      the same type and had an intraosseous length of 6.5 mm and a diameter of 4.0 mm.
      Twenty implants were additionally splinted onto longer ones. Measurements of
      marginal bone loss were performed at a mean of 12.38 months after prosthetic
      loading and the mean follow-up for clinical evaluation was 20.52 months. RESULTS:
      Overall two implant failures were recorded, revealing a survival rate of 97.3%.
      Marginal bone resorption around 72 short implants measured 0.71 mm (SD: 0.74 mm)
      and was found to have a strong correlation with calculated Crown-to-Implant ratio
      (r = .71; P < .001). Age, gender, insertion torque, implant surface area,
      location, position, bone quality, and insertion torque did not influence peri
      implant bone loss after one year of loading. CONCLUSION: Within the limitations
      of the study, it is suggested that Crown-to-Implant ratios should not exceed 1.7
      to avoid increased early marginal bone loss.

PMID- 29024304
TI  - Efficacy of alprostadil in preventing contrast-induced nephropathy in patients
      undergoing percutaneous coronary intervention: A multicenter prospective
      randomized controlled trial.
AB  - BACKGROUND: The role of alprostadil on the prevention of contrast-induced
      nephropathy (CIN) still remains controversial. The purpose of this study was to
      examine the effects of short-term alprostadil on the incidence of CIN in patients
      undergoing elective percutaneous coronary intervention (PCI). METHODS: A total of
      480 patients with coronary heart disease undergoing PCI were enrolled in our
      study and randomly assigned to two groups. The control group (n = 240) was given
      only hydration therapy and the alprostadil group (n = 240) received intravenous
      administration of 20 ug/day (diluted with 100 ml normal saline) from 0.5~1 hr
      before to 3 days after operation on the basis of hydration. The primary endpoint
      of the study was the incidence of CIN, which was defined as an increase in SCr
      concentration >= 44.2 umol/l or >=25% above baseline within 48 hr~72 hr after
      exposure of contrast media. RESULTS: The incidence of CIN was significantly lower
      in the alprostadil group than that in the control group (6.25% vs 11.67%, P =
      0.038). Multivariate logistic regression analysis showed that alprostadil was the
      protective factor of CIN (OR = 0.699, 95% CI 0.542-0.902, P = 0.006). The
      benefits against CIN were consistent in prespecified high-risk patients with
      diabetes mellitus (P = 0.003). In addition, we also found that hs-CRP and blood
      homocysteine values after PCI were significantly lower in the alprostadil group
      than those in the control group. CONCLUSION: Prophylactic administration of
      alprostadil may prevent against CIN in coronary heart disease patients undergoing
      elective PCI, particularly in high-risk patients with diabetes mellitus.

PMID- 29024302
TI  - Reduced electroencephalogram responses to standard and target auditory stimuli in
      bipolar disorder and the impact of psychotic features: Analysis of event-related
      potentials, spectral power, and inter-trial coherence.
AB  - BACKGROUND: Bipolar disorder (BD) is associated with reductions in the P3b event
      related potential (ERP) response to target auditory stimuli, which suggests
      deficits in context updating. Previous studies have typically examined these
      responses in the temporal domain, which may not capture alterations in specific
      frequencies of phase-locked or induced electrophysiological activity. Therefore,
      the present study examined early and late ERPs in temporal and frequency domains
      in a bipolar sample with and without current psychotic features. METHODS: The
      electroencephalogram (EEG) was recorded during an auditory oddball task. Seventy
      five BD patients and 98 healthy controls (HCs) discriminated between standard and
      target tones. N1 ERPs to standards and P3b ERPs to targets were analyzed in the
      temporal domain. Event-related spectral perturbation (ERSP) and inter-trial
      coherence (ITC) were analyzed in the frequency domain. RESULTS: The early N1
      response to standard tones was not significantly different between the total HC
      and BD samples irrespective of psychotic features. However, N1 amplitude was
      reduced in BD patients with psychotic features (BDP) compared to HCs and BD
      patients without psychotic features. P3b was reduced in BD patients versus HCs,
      with the BDP sample having the most reduced amplitude. In the time-frequency
      analysis, delta and theta ERSP and ITC were reduced across the time window for
      both standard and target stimuli in BD patients compared to HCs, but did not
      differ in the psychotic features analysis. CONCLUSIONS: The results provide
      neural evidence that BD is associated with disrupted sensory, attentional, and
      cognitive processing of auditory stimuli, which may be worsened with the presence
      of psychotic features.

PMID- 29024305
TI  - Catalytic Enantioselective Synthesis of Mariline A and Related Isoindolinones
      through a Biomimetic Approach.
AB  - The catalytic enantioselective synthesis of isoindolinones was achieved through
      the condensation of 2-acyl-benzaldehydes and anilines. In the presence of 1 mol %
      of a chiral phosphoric acid catalyst, reactions reach completion within 10 min
      and provide products with up to 98 % ee. Anilines with an ortho t-butyl group
      form atropisomeric products, thereby enabling the simultaneous generation of
      axial and point chirality from two achiral substrates. This method was applied to
      the first synthesis of mariline A.

PMID- 29024300
TI  - Accounting for the role of hematocrit in between-subject variations of MRI
      derived baseline cerebral hemodynamic parameters and functional BOLD responses.
AB  - Baseline hematocrit fraction (Hct) is a determinant for baseline cerebral blood
      flow (CBF) and between-subject variation of Hct thus causes variation in task
      based BOLD fMRI signal changes. We first verified in healthy volunteers (n = 12)
      that Hct values can be derived reliably from venous blood T1 values by comparison
      with the conventional lab test. Together with CBF measured using phase-contrast
      MRI, this noninvasive estimation of Hct, instead of using a population-averaged
      Hct value, enabled more individual determination of oxygen delivery (DO2 ),
      oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2 ).
      The inverse correlation of CBF and Hct explained about 80% of between-subject
      variation of CBF in this relatively uniform cohort of subjects, as expected based
      on the regulation of DO2 to maintain constant CMRO2 . Furthermore, we compared
      the relationships of visual task-evoked BOLD response with Hct and CBF. We showed
      that Hct and CBF contributed 22%-33% of variance in BOLD signal and removing the
      positive correlation with Hct and negative correlation with CBF allowed
      normalization of BOLD signal with 16%-22% lower variability. The results of this
      study suggest that adjustment for Hct effects is useful for studies of MRI
      perfusion and BOLD fMRI. Hum Brain Mapp 39:344-353, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29024306
TI  - Overview of glyphosate-resistant weeds worldwide.
AB  - Glyphosate is the most widely used and successful herbicide discovered to date,
      but its utility is now threatened by the occurrence of several glyphosate
      resistant weed species. Glyphosate resistance first appeared in Lolium rigidum in
      an apple orchard in Australia in 1996, ironically the year that the first
      glyphosate-resistant crop (soybean) was introduced in the USA. Thirty-eight weed
      species have now evolved resistance to glyphosate, distributed across 37
      countries and in 34 different crops and six non-crop situations. Although
      glyphosate-resistant weeds have been identified in orchards, vineyards,
      plantations, cereals, fallow and non-crop situations, it is the glyphosate
      resistant weeds in glyphosate-resistant crop systems that dominate the area
      infested and growing economic impact. Glyphosate-resistant weeds present the
      greatest threat to sustained weed control in major agronomic crops because this
      herbicide is used to control weeds with resistance to herbicides with other sites
      of action, and no new herbicide sites of action have been introduced for over 30
      years. Industry has responded by developing herbicide resistance traits in major
      crops that allow existing herbicides to be used in a new way. However, over
      reliance on these traits will result in multiple-resistance in weeds. Weed
      control in major crops is at a precarious point, where we must maintain the
      utility of the herbicides we have until we can transition to new weed management
      technologies. (c) 2017 Society of Chemical Industry.

PMID- 29024307
TI  - A Lewis Base Catalysis Approach for the Photoredox Activation of Boronic Acids
      and Esters.
AB  - We report herein the use of a dual catalytic system comprising a Lewis base
      catalyst such as quinuclidin-3-ol or 4-dimethylaminopyridine and a photoredox
      catalyst to generate carbon radicals from either boronic acids or esters. This
      system enabled a wide range of alkyl boronic esters and aryl or alkyl boronic
      acids to react with electron-deficient olefins via radical addition to
      efficiently form C-C coupled products in a redox-neutral fashion. The Lewis base
      catalyst was shown to form a redox-active complex with either the boronic esters
      or the trimeric form of the boronic acids (boroxines) in solution.

PMID- 29024308
TI  - Does remote monitoring change OSA management and CPAP adherence?
AB  - It is increasingly recognized that the high prevalence of obstructive sleep
      apnoea (OSA), and its associated cardio-metabolic morbidities make OSA a burden
      for society. Continuous positive airway pressure (CPAP), the gold standard
      treatment, needs to be used for more than 4 h/night to be effective, but suffers
      from relatively poor adherence. Furthermore, CPAP is likely to be more effective
      if combined with lifestyle changes. Thus, the remote telemonitoring (TM) of OSA
      patients in terms of CPAP use, signalling of device problems, following disease
      progression, detection of acute events and monitoring of daily physical activity
      is an attractive option. In the present review, we aim to summarize the recent
      scientific data on remote TM of OSA patients, and whether it meets expectations.
      We also look at how patient education and follow-up via telemedicine is used to
      improve adherence and we discuss the influence of the profile of the healthcare
      provider. Then, we consider how TM might be extended to encompass the patient's
      cardio-metabolic health in general. Lastly, we explore how TM and the deluge of
      data it potentially generates could be combined with electronic health records in
      providing personalized care and multi-disease management to OSA patients.

PMID- 29024309
TI  - Bio-prospecting endemic Mascarene Aloes for potential neuroprotectants.
AB  - The Mascarene Aloes are used in the traditional pharmacopoeia against various
      ailments including cutaneous diseases and as antispasmodics. Scientific evidence
      to support these claims is non-existent and mainly based on the scientific repute
      of A. vera. The antioxidant profile of methanolic leaf extracts of A. purpurea
      Lam., A. tormentorii (Marais) L. E. Newton & G. D. Rowley, A. lomatophylloides
      Balf. f., A. macra Haw. and A. vera (L.) Burm. f. was studied using the total
      antioxidant capacity, copper equivalent and superoxide dismutase assays. In vitro
      cytotoxicity was evaluated on CAD (Cath.-a-differentiated) neuronal cells by the
      methyl tetrazolium assay, and the neuroprotective profile was assessed using
      hydrogen peroxide-induced neurotoxicity with the CAD cells. The aloin and vitexin
      content were determined by high-performance liquid chromatography with diode
      array detection. A. purpurea had the highest aloin content (546.6 nmol/g), while
      A. tormentorii had the highest vitexin content (67.3 nmol/g). A. macra
      (concentration <0.1 mg/mL) elicited a 10% cytotoxicity effect on CAD cells while
      other Mascarene Aloes were not cytotoxic. This study validates the antioxidant
      and neuroprotective potential of Mascarene Aloes focusing on their aloin and
      vitexin content that are also present in other reputed medicinal Aloes.

PMID- 29024311
TI  - Collagen-inducing biologization of prosthetic material for hernia repair:
      Polypropylene meshes coated with polyP/collagen.
AB  - Prostethic mesh material such as nonabsorbable polypropylene used in open and
      laparoscopic hernia repair are characterized by controllable mechanical
      properties but may elicit undesirable physiological reactions due to the
      nonphysiological inert polymer material. We succeeded in developing a
      biocompatible coating for these meshes, based on a physiological inorganic
      polymer, polyphosphate (polyP) that is morphogenetically active and used as a
      metabolic energy source, and a collagen matrix. The polyP/collagen hydrogel
      material was prepared by a freeze-extraction method, with amorphous Ca-polyP
      microparticles. Electron microscopy (SEM and REM) studies revealed that the
      polyP/collagen coats are built up of ~50 nm-sized microparticles deposited onto
      the collagen matrix which forms a continuous layer around the polypropylene
      fibers that also spans the mesh pores. This bioresorbable inorganic/organic
      hybrid coat was found to be degraded during three days of incubation in
      medium/serum. The biomechanical properties of the coated meshes are comparable to
      those of the unmodified polypropylene meshes, with a higher toughness in
      longitudinal orientation and a more pronounced extensibility in the transverse
      orientation. The polyP/collagen coating improved cell attachment to the
      polypropylene meshes and strongly increase the growth of fibroblasts (MC3T3-E1
      cells). Furthermore, those mats upregulate the expression of the gene encoding
      the stromal cell-derived factor-1alpha (SDF-1), a mesenchymal stem cells
      attracting chemokine in the fibroblasts. We conclude that coating of inert
      polymer meshes with a biocompatible, collagen-inducing polyP/collagen
      inorganic/organic hybrid layer may improve tissue integration of the meshes and
      the outcome of surgical hernia repair and may redudce the foreign body reaction
      in contaminated field. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part
      B: Appl Biomater, 106B: 2109-2121, 2018.

PMID- 29024310
TI  - Influence of metabolic syndrome and race on the relationship between intensive
      blood pressure control and cardiovascular outcomes in the SPRINT cohort.
AB  - AIMS: To determine whether baseline metabolic syndrome (MetS) modifies the effect
      of intensive blood pressure control on cardiovascular (CV) outcomes, and whether
      the effects varied by race/ethnicity. METHODS: We performed post hoc analyses
      among non-Hispanic black, non-hispanic white and Hispanic participants, with and
      without MetS, in the Systolic Blood Pressure Intervention Trial (SPRINT), who
      were randomized to a systolic blood pressure (SBP) target of <120 mm Hg
      (intensive group, N = 4544) or an SBP target of <140 mm Hg (standard group, N =
      4553). The median follow-up was 3.26 years. The primary outcome was the composite
      of the first occurrence of myocardial infarction, stroke, heart failure, non
      myocardial infarction acute coronary syndrome or CV death. RESULTS: Overall,
      3521/9097 participants (38.7%) met the criteria for MetS at baseline. Baseline
      characteristics were similar in the two SBP target groups within each MetS
      subgroup, except body mass index was slightly higher in the standard arm of the
      MetS subgroup (33.3 +/- 5.6 vs 33.0 +/- 5.3 kg/m2 ; P < .01), but were similar
      across treatment arms in the non-MetS subgroup. The hazard ratio for the primary
      outcome was similarly reduced in participants with or without baseline MetS: 0.75
      (95% confidence interval [CI] 0.57, 0.96) and 0.71 (95% CI 0.57, 0.87),
      respectively (adjusted P value for treatment by subgroup interaction = .98).
      Similarly, there was no evidence of treatment * MetS subgroup interaction for all
      cause mortality (adjusted interaction P value = .98). The findings were also
      similar across race/ethnic subgroups. CONCLUSIONS: In this analysis the CV
      benefit of intensive SBP control did not differ among participants by baseline
      MetS status, regardless of race/ethnicity.

PMID- 29024312
TI  - Feeding forage mixtures of alfalfa hay and maize stover optimizes growth
      performance and carcass characteristics of lambs.
AB  - A feeding experiment was carried out to determine the effects of different
      proportions of alfalfa hay and maize stover on the growth performance and carcass
      characteristics of fattening lambs. Forty-two healthy 3.5-month-old male Small
      tail Han lambs of 23.89 +/- 0.38 kg body mass were assigned to seven groups,
      which were fed mixed diets composed of maize stover and alfalfa hay containing
      0%, 30%, 40%, 50%, 60%, 70% or 100% maize stover on a dry matter (DM) basis. Each
      lamb received 1.5 kg DM of forage mixture three times daily and supplementary
      concentrate (0.5 kg corn per lamb per day) for 60 days. Compared with the control
      forage diet of maize stover only, forage intake rate and forage conversion rate
      on the 40% maize stover/60% alfalfa hay mixture were 30% and 5% higher,
      respectively. Body weight, dressing percentage and net income were 6.7 kg, 8% and
      94.37 Yuan higher per lamb, respectively. Thus, feeding lambs with a forage
      mixture of maize stover and alfalfa hay in a ratio of 40:60 optimized the
      production performance, slaughter performance, and the income derived from lambs.

PMID- 29024313
TI  - Mesonephric remnant with seminal vesicle-like appearance in the cervix.

PMID- 29024314
TI  - Clinicomanometric factors associated with clinically relevant esophagogastric
      junction outflow obstruction from the Sandhill high-resolution manometry system.
AB  - BACKGROUND: Integrated relaxation pressure (IRP) is a key metric for diagnosing
      esophagogastric junction outflow obstruction (EGJOO). However, its normal value
      might be different according to the manufacturer of high-resolution manometry
      (HRM). This study aimed to investigate optimal value of IRP for diagnosing EGJOO
      in Sandhill HRM and to find clinicomanometric variables to segregate clinically
      relevant EGJOO. METHODS: We analyzed 262 consecutive subjects who underwent HRM
      between June 2011 and December 2016 showing elevated median IRP (> 15 mm Hg) but
      did not satisfy criteria for achalasia. Clinically relevant subjects were defined
      as follows: (i) subsequent HRM met achalasia criteria during follow-up (early
      achalasia); (ii) Eckardt score was decreased at least two points without
      exceeding a score of 3 after pneumatic dilatation (variant achalasia); and (iii)
      significant passage disturbance on esophagogram without structural abnormality
      (possible achalasia). KEY RESULTS: Seven subjects were clinically relevant,
      including two subjects with early achalasia, four subjects with variant
      achalasia, and one subject with possible achalasia. All clinically relevant
      subjects had IRP 20 mm Hg or above. Among subjects (n = 122) with IRP 20 mm Hg or
      more, clinically relevant group (n = 7) had significantly higher rate of
      dysphagia (100% vs 24.3%, P < .001) and compartmentalized pressurization (85.7%
      vs 21.7%, P = .001) compared to clinically non-relevant group (n = 115).
      CONCLUSIONS & INFERENCES: Our results suggest that IRP of 20 mm Hg or higher
      could segregate clinically relevant subjects showing EGJOO in Sandhill HRM.
      Additionally, if subjects have both dysphagia and compartmentalized
      pressurization, careful follow-up is essential.

PMID- 29024315
TI  - Copper-Catalyzed Synthesis of gamma-Amino Acids Featuring Quaternary
      Stereocenters.
AB  - The first general asymmetric synthesis of gamma,gamma-disubstituted gamma-amino
      acids by copper-catalyzed ring opening of nonstrained lactones with amines is
      reported. This approach features ample scope, operational simplicity, and wide
      functional-group diversity. The catalytic process allows access to a series of
      highly functionalized enantioenriched gamma-amino acids featuring quaternary
      stereocenters with excellent enantiomeric ratios of up to 98:2 and excellent
      yields of up to 98 %.

PMID- 29024316
TI  - Singlet Oxygen during Cycling of the Aprotic Sodium-O2 Battery.
AB  - Aprotic sodium-O2 batteries require the reversible formation/dissolution of
      sodium superoxide (NaO2 ) on cycling. Poor cycle life has been associated with
      parasitic chemistry caused by the reactivity of electrolyte and electrode with
      NaO2 , a strong nucleophile and base. Its reactivity can, however, not
      consistently explain the side reactions and irreversibility. Herein we show that
      singlet oxygen (1 O2 ) forms at all stages of cycling and that it is a main
      driver for parasitic chemistry. It was detected in- and ex-situ via a 1 O2 trap
      that selectively and rapidly forms a stable adduct with 1 O2 . The 1 O2 formation
      mechanism involves proton-mediated superoxide disproportionation on discharge,
      rest, and charge below ca. 3.3 V, and direct electrochemical 1 O2 evolution above
      ca. 3.3 V. Trace water, which is needed for high capacities also drives parasitic
      chemistry. Controlling the highly reactive singlet oxygen is thus crucial for
      achieving highly reversible cell operation.

PMID- 29024317
TI  - Camera traps and activity signs to estimate wild boar density and derive
      abundance indices.
AB  - BACKGROUND: Populations of wild boar and feral pigs are increasing worldwide, in
      parallel with their significant environmental and economic impact. Reliable
      methods of monitoring trends and estimating abundance are needed to measure the
      effects of interventions on population size. The main aims of this study, carried
      out in five English woodlands were: (i) to compare wild boar abundance indices
      obtained from camera trap surveys and from activity signs; and (ii) to assess the
      precision of density estimates in relation to different densities of camera
      traps. For each woodland, we calculated a passive activity index (PAI) based on
      camera trap surveys, rooting activity and wild boar trails on transects, and
      estimated absolute densities based on camera trap surveys. RESULTS: PAIs obtained
      using different methods showed similar patterns. We found significant between
      year differences in abundance of wild boar using PAIs based on camera trap
      surveys and on trails on transects, but not on signs of rooting on transects. The
      density of wild boar from camera trap surveys varied between 0.7 and 7
      animals/km2 . Increasing the density of camera traps above nine per km2 did not
      increase the precision of the estimate of wild boar density. CONCLUSION: PAIs
      based on number of wild boar trails and on camera trap data appear to be more
      sensitive to changes in population size than PAIs based on signs of rooting. For
      wild boar densities similar to those recorded in this study, nine camera traps
      per km2 are sufficient to estimate the mean density of wild boar. (c) 2017 Crown
      copyright. Pest Management Science (c) 2017 Society of Chemical Industry.

PMID- 29024318
TI  - Antiphospholipid antibody-induced cellular responses depend on epitope
      specificity : implications for treatment of antiphospholipid syndrome.
AB  - : Essentials Antiphospholipid antibodies (aPL) are heterogeneous and induce
      different cellular responses. We analyzed signaling events induced by different
      monoclonal and patient aPL in monocytes. Two major signaling pathways involving
      either NADPH-oxidase or LRP8 were identified. Our data suggest that these two
      pathways mediate the majority of aPL effects on monocytes. SUMMARY: Background
      Antiphospholipid antibodies (aPLs) contribute to the pathogenesis of the
      antiphospholipid syndrome (APS) by induction of an inflammatory and procoagulant
      state in different cell types, and several signaling pathways have been
      described. Objectives To investigate whether signaling depends on the epitope
      specificity of aPLs. Methods Cellular effects of three human monoclonal aPLs with
      distinctly different epitope specificities were analyzed in vitro. Expression of
      tumor necrosis factor-alpha mRNA by mouse and human monocytes was the major
      readout. Analysis included cells from genetically modified mice, and the use of
      specific inhibitors in human monocytes. Data were validated with IgG isolated
      from 20 APS patients. Results Cofactor-independent anticardiolipin aPLs activated
      monocytes by induction of endosomal NADPH oxidase. Activation could be blocked by
      hydroxychloroquine (HCQ). Anti-beta2 -glycoprotein I aPL activated monocytes by
      interacting with LDL receptor-related protein 8 (LRP8). This could be blocked by
      rapamycin. Analysis of 20 APS patients' IgG showed that all IgG fractions
      activated the same two pathways as the monoclonal aPL, depending on their epitope
      patterns as determined by ELISA. Monocyte activation by APS IgG could be blocked
      completely by HCQ and/or rapamycin, suggesting that in most, if not all, APS
      patients there is no other relevant signaling pathway. Conclusions aPLs activate
      two major proinflammatory signal transduction pathways, depending on their
      epitope specificity. HCQ and rapamycin, either alone or in combination,
      completely suppress signaling by APS IgG. These observations may provide a
      rationale for specific treatment of APS patients according to their aPL profile.

PMID- 29024319
TI  - Prognostic significance of Glasgow prognostic score in patients with acute
      exacerbation of idiopathic pulmonary fibrosis.
AB  - BACKGROUND AND OBJECTIVE: The Glasgow prognostic score (GPS) reflects the host
      systemic inflammatory response and is a validated independent prognostic factor
      in lung cancer. We investigated GPS as a potential predictive factor of clinical
      outcomes in idiopathic pulmonary fibrosis (IPF) patients with acute exacerbation
      (AE). METHODS: This was a retrospective study performed between January 2006 and
      March 2016 in Bucheon St. Mary's Hospital, The Catholic University of Korea.
      Overall, 327 admitted IPF patients were registered in the study. Patients with
      definite pneumonia at the time of admission, those with left-sided heart failure,
      pulmonary embolism and an identifiable cause of acute lung injury, and those
      whose albumin or C-reactive protein levels were not measured were excluded.
      RESULTS: A total of 66 patients hospitalized with IPF-AE were finally included.
      Median survival was 20.7 days and 29 (43.9%) patients died during
      hospitalization. The median length of overall survival (OS) was 26.0, 20.0 and
      15.0 days for GPS-0, GPS-1 and GPS-2, respectively. There were significant
      differences in OS between GPS-0 and GPS-2 (P = 0.002). In a multivariate analysis
      performed using a Cox regression model, eosinopenia (P = 0.007), lower partial
      pressure of oxygen/fraction of inspired oxygen ratio (P = 0.014), and higher GPS
      (P = 0.006) were independent predictors of mortality. CONCLUSION: GPS can be
      helpful in predicting mortality in IPF patients with AE.

PMID- 29024320
TI  - Band-Gap Engineering of Graphene Heterostructures by Substitutional Doping with
      B3 N3.
AB  - We investigated the energetics and electronic structure of B3 N3 -doped graphene
      employing density functional theory calculations with the generalized gradient
      approximation. Our calculations reveal that all of the B3 N3 -doped graphene
      structures are semiconducting, irrespective of the periodicity of the B3 N3
      embedded into the graphene network. This is in contrast to graphene nanomeshes,
      which are either semiconductors or metals depending on the mesh arrangement. In
      B3 N3 -doped graphene, the effective masses for both electrons and holes are
      small. The band gap in the B3 N3 -doped graphene networks and the total energy of
      the B3 N3 -doped graphene are inversely proportional to the B3 N3 spacing.
      Furthermore, both properties depend on whether or not the graphene region
      possesses a Clar structure. In particular, the sheets with a Clar structure
      exhibit a wider band gap and a slightly lower total energy than those without a
      Clar structure.

PMID- 29024324
TI  - Clinical implications of gastrointestinal symptoms in systemic amyloidosis.
AB  - BACKGROUND: Gastrointestinal (GI) symptoms in systemic amyloidosis patients are
      poorly characterized. This purpose of this study is to define the epidemiology
      and clinical implications of such symptoms. METHODS: This was a retrospective
      cohort study of 583 amyloid patients seen at a tertiary referral center. Of 96
      symptomatic patients, 82 received endoscopic biopsies, subsequently grouped into
      those with histologic evidence of GI amyloid (biopsy proven) vs without (biopsy
      absent). KEY RESULTS: 16.8% of patients had GI symptoms, and had more abnormal NT
      proBNP, cardiac ejection fraction, serum albumin, and alkaline phosphatase (P <
      .01). Of those who received endoscopy, the sites of highest diagnostic yield were
      stomach, duodenum and colon. The most common symptom was abdominal pain, nausea,
      or vomiting (50.0%). Of the symptomatic patients, only 37 (45%) had biopsy proven
      GI amyloid. Biopsy proven patients more often had cardiac involvement (P < .005),
      and more often received hematologic therapy or transplant (P = .01). Biopsy
      absent patients had more frequent neurologic involvement (P = .17). Biopsy status
      had no significant correlation with other indicators of amyloid burden, GI
      symptoms or management. CONCLUSIONS & INFERENCES: Nearly one in six amyloid
      patients have GI symptoms, and half do not have GI amyloid. The type of symptom
      does not predict endoscopic findings. Most biopsy absent patients are not managed
      as a functional disorder despite no alternative etiology. Gastroenterologists may
      have an increased role to play in the care of systemic amyloidosis beyond
      performing endoscopies, such as evaluating cardiac amyloid patients for
      concurrent GI amyloid.

PMID- 29024323
TI  - Excretion of Avenanthramides, Phenolic Acids and their Major Metabolites
      Following Intake of Oat Bran.
AB  - SCOPE: Wholegrain has been associated with reduced chronic disease mortality,
      with oat intake particularly notable for lowering blood cholesterol and glycemia.
      To better understand the complex nutrient profile of oats, we studied urinary
      excretion of phenolic acids and avenanthramides after ingestion of oat bran in
      humans. METHODS AND RESULTS: After a 2-d (poly)phenol-low diet, seven healthy men
      provided urine 12 h before and 48 h after consuming 60 g oat bran (7.8 MUmol
      avenanthramides, 139.2 MUmol phenolic acids) or a phenolic-low (traces of
      phenolics) control in a crossover design. Analysis by ultra-high performance
      liquid chromatography (UPLC)-MS/MS showed that oat bran intake resulted in an
      elevation in urinary excretion of 30 phenolics relative to the control,
      suggesting that they are oat bran-derived. Mean excretion levels were elevated
      between 0-2 and 4-8 h, following oat bran intake, and amounted to a total of 33.7
      +/- 7.3 MUmol total excretion (mean recovery: 22.9 +/- 5.0%), relative to
      control. The predominant metabolites included: vanillic acid, 4- and 3
      hydroxyhippuric acids, and sulfate-conjugates of benzoic and ferulic acids, which
      accounted collectively for two thirds of total excretion. CONCLUSION: Oat bran
      phenolics follow a relatively rapid urinary excretion, with 30 metabolites
      excreted within 8 h of intake. These levels of excretion suggest that bound
      phenolics are, in part, rapidly released by the microbiota.

PMID- 29024321
TI  - Post-Graphene 2D Chemistry: The Emerging Field of Molybdenum Disulfide and Black
      Phosphorus Functionalization.
AB  - The current state of the chemical functionalization of three types of single
      sheet 2D materials, namely, graphene, molybdenum disulfide (MoS2 ), and black
      phosphorus (BP) is summarized. Such 2D sheet polymers are currently an emerging
      field at the interface of synthetic chemistry, physics, and materials science.
      Both covalent and non-covalent functionalization of sheet architectures allows a
      systematic modification of their properties, that is, an improvement of
      solubility and processability, the prevention of re-aggregation, or band-gap
      tuning. Next to successful functionalization concepts, fundamental challenges are
      also addressed. These include the insolubility and polydispersity of most 2D
      sheet polymers, the development of suitable characterization tools, the
      identification of effective binding strategies, the chemical activation of the
      usually rather unreactive basal planes for covalent addend binding, and the
      regioselectivity of plane addition reactions. Although a number of these
      questions remain elusive in this Review, the first promising concepts to overcome
      such hurdles are presented.

PMID- 29024325
TI  - Dose-Response Effects of p-Synephrine on Fat Oxidation Rate During Exercise of
      Increasing Intensity.
AB  - The aim of this investigation was to determine the effects different doses of p
      synephrine on maximal fat oxidation during exercise. Seventeen healthy subjects
      volunteered to participate in a double-blind and randomised experimental design
      composed of four identical experimental trials. On four trials separated by 72 h,
      participants ingested a placebo or 1, 2 or 3 mg/kg of p-synephrine. After resting
      for 60 min to allow substance absorption, participants performed an exercise test
      of increasing intensity on a cycle ergometer while gas exchange was measured
      continuously. None of the doses of p-synephrine affected energy expenditure or
      heart rates during the test. The highest rate of fat oxidation with the placebo
      (0.35 +/- 0.05 g/min) was reached at 38.0 +/- 1.9% of VO2max . The ingestion of 1
      mg/kg increased maximal fat oxidation to 0.47 +/- 0.11 g/min (p = 0.01) but did
      not change the intensity at which it was obtained (42.0 +/- 9.4% of VO2max ). The
      ingestion of 2 and 3 mg/kg of p-synephrine increased maximal fat oxidation to
      0.55 +/- 0.14 g/min (p < 0.01), although only 3 mg/kg slightly changed the
      intensity at which it was obtained (43.0 +/- 9.5% of VO2max , p < 0.01). In
      conclusion, although all p-synephrine increased the maximal rate of fat oxidation
      during exercise, the highest effects were found with 2 and 3 mg/kg. Copyright (c)
      2017 John Wiley & Sons, Ltd.

PMID- 29024322
TI  - Not in your usual Top 10: protists that infect plants and algae.
AB  - Fungi, nematodes and oomycetes belong to the most prominent eukaryotic plant
      pathogenic organisms. Unicellular organisms from other eukaryotic lineages,
      commonly addressed as protists, also infect plants. This review provides an
      introduction to plant pathogenic protists, including algae infecting oomycetes,
      and their current state of research.

PMID- 29024326
TI  - CODH-IV: A High-Efficiency CO-Scavenging CO Dehydrogenase with Resistance to O2.
AB  - CO dehydrogenases (CODHs) catalyse the reversible conversion between CO and CO2 .
      Genomic analysis indicated that the metabolic functions of CODHs vary. The genome
      of Carboxydothermus hydrogenoformans encodes five CODHs (CODH-I-V), of which CODH
      IV is found in a gene cluster near a peroxide-reducing enzyme. Our kinetic and
      crystallographic experiments reveal that CODH-IV differs from other CODHs in
      several characteristic properties: it has a very high affinity for CO, oxidizes
      CO at diffusion-limited rate over a wide range of temperatures, and is more
      tolerant to oxygen than CODH-II. Thus, our observations support the idea that
      CODH-IV is a CO scavenger in defence against oxidative stress and highlight that
      CODHs are more diverse in terms of reactivity than expected.

PMID- 29024327
TI  - Effect of a See and Treat clinic on skin cancer treatment time.
AB  - BACKGROUND: Many plastic surgery departments in Australasia have experienced
      increasing referrals for management of skin lesions. This has driven a demand for
      new strategies to decrease patient waiting time and administrative costs. The aim
      of this study was to determine if a purpose-built See and Treat skin cancer
      clinic could provide a faster skin cancer treatment pathway with comparable
      clinical outcomes and acceptability to patients. METHODS: This was a prospective
      observational study of patients treated through the See and Treat clinic with a
      retrospective control cohort. The prospective 'See and Treat' cohort included a
      consecutive series of 106 patients, while the retrospective cohort included a
      consecutive series of 200 patients. Patient demographics, time from referral to
      surgery and operative measures were analysed. One hundred patients in the
      prospective cohort completed an anonymous satisfaction survey regarding their
      treatment. RESULTS: The average time from referral to surgery was reduced from
      121 days in the retrospective cohort to 60 days in the See and Treat cohort (P <
      0.001). Rates of complete excision of malignant and premalignant lesions were not
      different between the two groups, being 93% (178/191) and 91% (76/84),
      respectively (P = 0.609). Ninety-five percent (95/100) of patients were satisfied
      with their See and Treat experience overall. CONCLUSION: We show that a
      considerable reduction in the time between referral and surgery can be achieved
      through a See and Treat clinic without compromise of the success of surgical
      treatment. Moreover, such a treatment pathway has been shown to be acceptable,
      and largely preferable, to patients.

PMID- 29024328
TI  - The development of morphological representations in young readers: a cross-modal
      priming study.
AB  - The way children organize words in their memory has intrigued many researchers in
      the past 20 years. Given the large number of morphologically complex words in
      many languages, the influence of morphemes on this organization is being
      increasingly examined. The aim of this study was to understand how morphemic
      information influences English-speaking children's word recognition. Children in
      grades 3 and 5 were asked to complete a lexical decision priming task. Prime
      target pairs varied in semantic similarity, with low (e.g., belly-bell), moderate
      (e.g., lately-late), and high similarity relations (e.g., boldly-bold). There
      were also word pairs similar in form only (e.g., spinach-spin) and in semantics
      only (e.g., garbage-trash). Primes were auditory and targets were presented
      visually. Analyses of children's lexical decision times revealed graded priming
      effects as a function of the convergence of form and meaning. These results
      indicate that developing readers do not necessarily need to lexicalize
      morphological units to facilitate word recognition. Their ability to process the
      morphological structure of words depends on their ability to develop connections
      between form and meaning.

PMID- 29024329
TI  - Direct Readout of Single Nucleobase Variations in an Oligonucleotide.
AB  - Direct, low-cost, label-free, and enzyme-free identification of single nucleobase
      is a great challenge for genomic studies. Here, this study reports that wild-type
      aerolysin can directly identify the difference of four types of single nucleobase
      (adenine, thymine, cytosine, and guanine) in a free DNA oligomer while avoiding
      the operations of additional DNA immobilization, adapter incorporation, and the
      use of the processing enzyme. The nanoconfined space of aerolysin enables DNA
      molecules to be limited in the narrow pore. Moreover, aerolysin exhibits an
      unexpected capability of detecting DNA oligomers at the femtomolar concentration.
      In the future, by virtue of the high sensitivity of aerolysin and its high
      capture ability for DNA oligomers, aerolysin will play an important role in the
      studies of single nucleobase variations and open up new avenues for a broad range
      of nucleic-acid-based sensing and disease diagnosis.

PMID- 29024330
TI  - C-H Functionalisation for Hydrogen Isotope Exchange.
AB  - The various applications of hydrogen isotopes (deuterium, D, and tritium, T) in
      the physical and life sciences demand a range of methods for their installation
      in an array of molecular architectures. In this Review, we describe recent
      advances in synthetic C-H functionalisation for hydrogen isotope exchange.

PMID- 29024331
TI  - Detection of latent infections caused by Colletotrichum sp. in olive fruit.
AB  - AIMS: To set up a practical method to detect latent infections of Colletotrichum
      sp., the causal agent of olive anthracnose, on olives before the onset of disease
      symptoms. METHODS AND RESULTS: Freezing, sodium hydroxide (NaOH), ethanol and
      ethylene treatments were evaluated to detect latent infections on inoculated and
      naturally infected olive fruit by Colletotrichum sp. as non-hazardous
      alternatives to paraquat. Treatments were conducted using fruit of cultivars
      Arbequina and Hojiblanca. The disease incidence and T50 were calculated. Dipping
      in NaOH 0.05% solution and the paraquat method were the most effective treatments
      on both inoculated and naturally infected fruit, although the value of T50 was
      lower for the NaOH method than for the paraquat method in one of the experiments.
      Subsequently, the dipping time in NaOH 0.05% was evaluated. Longer dipping times
      in NaOH 0.05% were better than shorter ones in cultivar Arbequina, with 72 h
      being the most effective in cultivar Hojiblanca. CONCLUSIONS: NaOH solution is a
      practical method to detect latent infections of Colletotrichum sp. on immature
      olive fruit. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is relevant because
      we set up a viable, non-hazardous alternative to paraquat to detect latent
      infections of Colletotrichum sp. using NaOH. The use of NaOH is a simple and eco
      friendly tool that allows the determination of the level of latent infections by
      Colletotrichum in olives. Therefore, our method will be useful in decision-making
      processes for disease management before the appearance of the first visible
      symptoms.

PMID- 29024332
TI  - Effect of resistance training set volume on upper body muscle hypertrophy: are
      more sets really better than less?
AB  - BACKGROUND: Resistance training (RT) for upper body muscle hypertrophy (UBMH)
      typically entails high volumes of sets per muscle group per training session. The
      majority of RT regimens does not discriminate between upper and lower body muscle
      groups, while these groups may respond differently to RT set volumes in terms of
      maximum skeletal muscle mass gain. Recent studies have examined the effect of
      different set volumes on the extent of UBMH to formulate optimal RT regimens and
      to make RT programmes more time-efficient. OBJECTIVE: To analyse the effect of
      the number of RT sets on the extent of UBMH on the basis of recent literature.
      RESULTS AND CONCLUSION: The analysis suggests that, statistically, high set
      volumes (>=3) are not significantly better than low set volumes (<3) in regard to
      UBMH in untrained subjects. For trained subjects, the literature is lacking in
      well-designed studies comparing low and high training volumes, as well as
      analysing upper and lower body muscles separately. Therefore, it is not possible
      to conclude that high volume of sets offers better results than low volume of
      sets for UBMH, and vice versa.

PMID- 29024333
TI  - United we stand, divided we conquer: pilot study of multidisciplinary General
      Medicine Heart Failure Care Program.
AB  - BACKGROUND: Heart failure care and education require a multifaceted approach to
      ensure appropriate transition from inpatient to outpatient care. AIMS: To explore
      the feasibility of a multidisciplinary heart failure care model, General Medicine
      Heart Failure Care Program (GM-HFCP), within a General Medical Unit (GMU).
      METHODS: Prospective non-randomised before-and-after observational quality
      improvement intervention over a 6-month period was conducted. All consecutive
      patients admitted to GMU at Alfred Hospital, Melbourne with a diagnosis of acute
      decompensated heart failure were included. Main outcome measures included changes
      in rates of pharmacologic prescription, non-pharmacologic ward-based management,
      patient education and action plan provision after intervention. RESULTS: In
      total, 108 patients were included (median age 84 (inter-quartile range 80-89)
      years, 47(44%) females). Significant improvements were noted in non-pharmacologic
      management for patient education regarding fluid restriction (12-30%, P = 0.04),
      weight monitoring (10-28%, P = 0.03), heart failure action plan on discharge (4
      28%, P = 0.002) and salt restriction (6-32%, P = 0.002). The rates of
      prescription of heart failure medications remained similar between the pre- and
      post-implementation periods, particularly in patients with reduced ejection
      fraction by 'appropriateness of prescription' criteria. There were no differences
      in inpatient mortality or 30-day readmission rates in both groups. CONCLUSIONS:
      This prospective observational study demonstrated that it is possible to share
      the roles of a heart failure nurse amongst members of the multidisciplinary team,
      with similar rates of delivery of pharmacologic and non-pharmacologic management
      aspects. However, further innovative improvements are needed to address certain
      aspects of heart failure care.

PMID- 29024334
TI  - Intermediate and nonclassical monocytes show heterogeneity in patients with
      different types of acute coronary syndrome.
AB  - This study was performed to gain further insight in the heterogeneity of
      monocytes in the different categories of acute coronary syndrome (ACS),
      especially between patients with unstable angina pectoris, ST-elevation
      myocardial infarction (STEMI), and non-ST-elevation myocardial infarction
      (NSTEMI). For this purpose, blood samples were collected in the acute phase from
      patients presenting with an ACS. These samples were examined with multiparameter
      flow cytometry to identify the different monocyte subsets and to analyze the
      expression of monocyte-associated molecules. Leukocytes, as well as an absolute
      number of monocytes, showed a clear and significant increase in patients with
      STEMI. This increase was seen in all subtypes of monocytes. The classical
      monocytes (CD14++CD16-) of patients with an NSTEMI had a significantly increased
      CD11b expression when compared to the control group, while these cells showed a
      decreased expression pattern in STEMI patients. This increased CD11b-expression
      was also seen in the intermediate monocytes of NSTEMI, while it was almost
      completely downregulated on the intermediate monocytes of STEMI. Finally, CX3CR1,
      which is almost exclusively expressed on intermediate and nonclassical monocytes,
      showed a significant decrease in expression in patients with STEMI. In
      conclusion, intermediate and nonclassical monocytes have a different
      immunophenotypic pattern in patients with STEMI versus NSTEMI. These differences
      reflect the pro-inflammatory state of the monocytes in NSTEMI and can be used as
      target molecules for novel therapeutic strategies to diminish the migration of
      proinflammatory monocytes into the myocardial tissue. (c) 2017 International
      Society for Advancement of Cytometry.

PMID- 29024335
TI  - Fifty shades of SUMO: its role in immunity and at the fulcrum of the growth
      defence balance.
AB  - The sessile nature of plants requires them to cope with an ever-changing
      environment. Effective adaptive responses require sophisticated cellular
      mechanisms at the post-transcriptional and post-translational levels. Post
      translational modification by small ubiquitin-like modifier (SUMO) proteins is
      emerging as a key player in these adaptive responses. SUMO conjugation can
      rapidly change the overall fate of target proteins by altering their stability or
      interaction with partner proteins or DNA. SUMOylation entails an enzyme cascade
      that leads to the activation, conjugation and ligation of SUMO to lysine residues
      of target proteins. In addition to their SUMO processing activities, SUMO
      proteases also possess de-conjugative activity capable of cleaving SUMO from
      target proteins, providing reversibility and buffering to the pathway. These
      proteases play critical roles in the maintenance of the SUMO machinery in
      equilibrium. We hypothesize that SUMO proteases provide the all-important
      substrate specificity within the SUMO system. Furthermore, we provide an overview
      of the role of SUMO in plant innate immunity. SUMOylation also overlaps with
      multiple growth-promoting and defence-related hormone signalling pathways, and
      hence is pivotal for the maintenance of the growth-defence balance. This review
      aims to highlight the intricate molecular mechanisms utilized by SUMO to regulate
      plant defence and to stabilize the growth-defence equilibrium.

PMID- 29024337
TI  - 'Two-floret spikelet' as a novel resource has the potential to increase rice
      yield.

PMID- 29024336
TI  - Interplay of pathogenic forms of human tau with different autophagic pathways.
AB  - Loss of neuronal proteostasis, a common feature of the aging brain, is
      accelerated in neurodegenerative disorders, including different types of
      tauopathies. Aberrant turnover of tau, a microtubule-stabilizing protein,
      contributes to its accumulation and subsequent toxicity in tauopathy patients'
      brains. A direct toxic effect of pathogenic forms of tau on the proteolytic
      systems that normally contribute to their turnover has been proposed. In this
      study, we analyzed the contribution of three different types of autophagy,
      macroautophagy, chaperone-mediated autophagy, and endosomal microautophagy to the
      degradation of tau protein variants and tau mutations associated with this age
      related disease. We have found that the pathogenic P301L mutation inhibits
      degradation of tau by any of the three autophagic pathways, whereas the risk
      associated tau mutation A152T reroutes tau for degradation through a different
      autophagy pathway. We also found defective autophagic degradation of tau when
      using mutations that mimic common posttranslational modifications in tau or known
      to promote its aggregation. Interestingly, although most mutations markedly
      reduced degradation of tau through autophagy, the step of this process
      preferentially affected varies depending on the type of tau mutation. Overall,
      our studies unveil a complex interplay between the multiple modifications of tau
      and selective forms of autophagy that may determine its physiological degradation
      and its faulty clearance in the disease context.

PMID- 29024338
TI  - Regulating DNA Self-assembly by DNA-Surface Interactions.
AB  - DNA self-assembly provides a powerful approach for preparation of nanostructures.
      It is often studied in bulk solution and involves only DNA-DNA interactions. When
      confined to surfaces, DNA-surface interactions become an additional, important
      factor to DNA self-assembly. However, the way in which DNA-surface interactions
      influence DNA self-assembly is not well studied. In this study, we showed that
      weak DNA-DNA interactions could be stabilized by DNA-surface interactions to
      allow large DNA nanostructures to form. In addition, the assembly can be
      conducted isothermally at room temperature in as little as 5 seconds.

PMID- 29024339
TI  - Fracturing a dysfunctional Edwards Perimount bioprosthetic valve to facilitate
      percutaneous valve-in-valve placement of SAPIEN 3 valve with modified delivery
      system.
AB  - Pulmonary valve replacement via surgical implantation of a bioprosthetic valve
      (BPV) is a well-established treatment for patients with dysfunctional RV outflow
      tracts. BPVs are prone to structural deterioration, and will eventually require
      replacement. Recently, percutaneous valve-in-valve (VIV) placement of
      transcatheter valves has established itself as a safe and effective alternative
      to surgical revision. Unfortunately, VIV therapy is inherently limited by the
      inner diameter of the BPV, which restricts the number of eligible patients. Other
      centers have reported on the feasibility of cracking certain BPVs with ultra high
      pressure balloons in bench testing. We now report cracking an Edwards Perimount
      BPV in the pulmonary position to facilitate VIV placement of an Edwards SAPIEN 3.
      The ability to crack the Perimount valve allowed placement of a larger valve than
      previously considered and minimized the final valve gradient. In an effort to
      avoid the morbidity and mortality of surgical pulmonary valve replacement, this
      new strategy will expand the number of patients eligible for percutaneous VIV
      therapy.

PMID- 29024341
TI  - Modulation of Human Subcutaneous Adipose Tissue MicroRNA Profile Associated with
      Changes in Adiposity-Related Parameters.
AB  - SCOPE: To analyze the effect of three calorie-restricted diets with different
      amount and quality of carbohydrates on subcutaneous adipose tissue (SAT) microRNA
      (miRNA) profile. METHODS AND RESULTS: 6-month parallel, randomized trial
      conducted on overweight and obese subjects randomized to: 1) low glycemic index
      diet (LGI), 2) high glycemic index diet (HGI), and 3) low-fat (LF). The genome
      wide SAT miRNA profile was assessed in eight randomly selected participants and
      the most relevant changing miRNAs (n = 13) were validated in 48 subjects. None of
      the miRNAs showed significant changes between the intervention groups. However,
      changes in some of them correlated with changes in biochemical and anthropometric
      variables. Stratifying our population according to tertiles of percentage change
      in body weight (BW), we observed a significant down-regulation of miR-210 in
      those subjects in Tertile 1 as compared to Tertile 3. When our population was
      stratified by tertiles of waist circumference, miR-132, miR-29a, miR-34a, and miR
      378 were found to be significantly down-regulated, in T2 compared to T3.
      Furthermore, when stratified by tertiles of fat mass, we also observed the
      significant down-regulation of miR-132 in T1. CONCLUSION: The macronutrient
      composition of a calorie-restricted diet does not affect the expression of the
      miRNAs analyzed, while changes in adiposity play a primary regulatory role.

PMID- 29024342
TI  - Upconversion Nanocarriers Encapsulated with Photoactivatable Ru Complexes for
      Near-Infrared Light-Regulated Enzyme Activity.
AB  - Enzyme activity is important for metabolism, cell functions, and treating
      diseases. However, remote control of enzyme activity in deep tissue remains a
      challenge. This study demonstrates near-infrared (NIR) light-regulated enzyme
      activity in living cells based on upconverting nanoparticles (UCNPs) and a
      photoactivatable Ru complex. The Ru complex is a caged enzyme inhibitor that can
      be activated by blue light. To prepare a nanocarrier for NIR photoinhibition of
      enzyme activity, a UCNP and the caged enzyme inhibitors are encapsulated in a
      hollow mesoporous silica nanoparticle. In such a nanocarrier, the UCNP can
      harvest NIR light and convert it into blue light, which can activate the caged
      enzyme inhibitors. This photoactivation process is feasible in deep tissue
      because of the tissue penetration ability of NIR light. The nanocarrier is
      compatible to LNCaP, PC3, and SAOS-2 cells, which show high enzyme expression.
      NIR irradiation induces release of the inhibitors and inhibition of enzyme
      activity in living cells. NIR light provides high spatiotemporal resolution to
      regulate enzyme activity in deep tissue.

PMID- 29024340
TI  - Multiple marker abundance profiling: combining selected reaction monitoring and
      data-dependent acquisition for rapid estimation of organelle abundance in
      subcellular samples.
AB  - Measuring changes in protein or organelle abundance in the cell is an essential,
      but challenging aspect of cell biology. Frequently-used methods for determining
      organelle abundance typically rely on detection of a very few marker proteins, so
      are unsatisfactory. In silico estimates of protein abundances from publicly
      available protein spectra can provide useful standard abundance values but
      contain only data from tissue proteomes, and are not coupled to organelle
      localization data. A new protein abundance score, the normalized protein
      abundance scale (NPAS), expands on the number of scored proteins and the scoring
      accuracy of lower-abundance proteins in Arabidopsis. NPAS was combined with
      subcellular protein localization data, facilitating quantitative estimations of
      organelle abundance during routine experimental procedures. A suite of targeted
      proteomics markers for subcellular compartment markers was developed, enabling
      independent verification of in silico estimates for relative organelle abundance.
      Estimation of relative organelle abundance was found to be reproducible and
      consistent over a range of tissues and growth conditions. In silico abundance
      estimations and localization data have been combined into an online tool,
      multiple marker abundance profiling, available in the SUBA4 toolbox
      (http://suba.live).

PMID- 29024344
TI  - Authors' reply re: The impact of a novel transendometrial approach for caesarean
      myomectomy on obstetric outcomes of subsequent pregnancy: a longitudinal panel
      study.

PMID- 29024343
TI  - Dimensionality and internal structure of the Colombian version of the INICO-FEAPS
      quality of life scale.
AB  - BACKGROUND AND OBJECTIVE: Measuring quality of life (QoL) in people with
      intellectual disabilities (IDs) can help organisations and practitioners to
      implement evidence-based practices and develop person-centred planning and
      individualised supports. There is no reliable and valid instrument for assessing
      QoL in people with ID in Colombia. We investigated the internal structure of the
      Colombian version of the INICO-FEAPS scale and tested whether the scale
      identified the eight interrelated domains of the QoL conceptual framework
      originally described by. METHOD: Data were collected from 602 adults with
      moderate levels of ID and respective proxies, who completed the self-report and
      the report by other scales, respectively. Five measurement models were tested
      through confirmatory factor analysis. RESULTS: The eight correlated dimension
      model showed the best fit to the data. Reliability and convergent validity of the
      indicators were satisfactory in both versions of the scale (self-report and proxy
      report). CONCLUSIONS: This study contributes to research on QoL measurement by
      providing the first empirical evidence regarding the dimensionality, internal
      structure and psychometric properties of the Colombian version of the INICO-FEAPS
      scale. Moreover, the study presents the first adaptation of a specific QoL scale
      for people with ID in Colombia, which may in the future be useful for
      implementing evidence-based practices and developing person-centred support
      plans.

PMID- 29024345
TI  - Effect of Water Addition during Preparation on the Early-Time Photodynamics of
      CH3 NH3 PbI3 Perovskite Layers.
AB  - The effect of water addition during preparation of a CH3 NH3 PbI3 layer on the
      photodynamics is studied by femtosecond transient absorption. Both the regular
      perovskite and the aqueous analogue show charge thermalisation on a timescale of
      about 500 fs. This process is, however, less pronounced in the latter layer. The
      spectral feature associated with hot charges does not fully decay on this
      timescale, but also shows a long-lived (sub-ns) component. As water molecules may
      interfere with the hydrogen bonding between the CH3 NH3+ cations and the
      inorganic cage, this effect is possibly caused by immobilisation of cation
      motion, suggesting a key role of CH3 NH3+ dipole reorientation in charge
      thermalisation. This effect shows the possibility of controlling hot charge
      carrier cooling to overcome the Shockley-Queisser limit.

PMID- 29024346
TI  - Dementia assessment services: What are the perceptions of older people?
AB  - OBJECTIVE: To determine how older people with dementia and their family
      caregivers experience dementia assessment services and preferences for future
      configuration of diagnostic services. METHODS: Qualitative, semistructured in
      depth interviews were conducted with nine individuals with dementia. In seven
      instances, the caregiver also took part in the interview, and on two occasions,
      the interview was with the person with dementia only. RESULTS: An important
      contact during assessment of dementia was the general practitioner, in particular
      working in a way or timeframe which provides clarity and comfort to the person
      with dementia and their family members. A problematic factor in clear diagnosis
      was when probable dementia was suspected during hospitalisation for another
      complaint. Participants expressed a wide range of views in terms of preferred
      settings for diagnostic services. CONCLUSION: These findings highlight some key
      considerations, which should be included in future research leading to decisions
      about the design of dementia client services.

PMID- 29024347
TI  - Longterm outcome of rendezvous technique for hepaticojejunal anastomotic
      obstruction after pediatric living donor liver transplantation.

PMID- 29024348
TI  - Obesity as a risk factor for Alzheimer's disease: weighing the evidence.
AB  - Alzheimer's disease (AD) is the sixth leading cause of death in the USA today;
      therefore, it is imperative that public health initiatives and clinical
      strategies are developed to prevent and effectively treat AD. Despite the
      enormous impact that AD has on individuals, families, society, and the health
      care system, there are no biomarkers to clearly identify those at risk for AD,
      public health prevention strategies in place, or treatments to address the
      underlying pathology or stop the progression of AD. There is ample scientific as
      well as empirical evidence that obesity and its metabolic and vascular
      comorbidities are related to AD and likely in the causative pathway. Obesity
      prevention and treatment could prove to be an efficacious and safe approach to
      preventing AD, a serious and daunting epidemic disease. In this review, we
      present the current pathophysiological and clinical evidence linking obesity and
      obesity-related comorbidities (eg, insulin resistance, hyperglycaemia, and type 2
      diabetes) with AD. Additionally, we discuss which population to target and when
      to consider treatment for AD. Finally, we summarize the current evidence
      regarding the efficacy of anti-obesity and anti-diabetic pharmacotherapeutic
      agents for the treatment of AD.

PMID- 29024349
TI  - Visible-Light-Driven Iron-Promoted Thiocarboxylation of Styrenes and Acrylates
      with CO2.
AB  - The first thiocarboxylation of styrenes and acrylates with CO2 was realized by
      using visible light as a driving force and catalytic iron salts as promoters. A
      variety of important beta-thioacids were obtained in high yields. This
      multicomponent reaction proceeds in an atom- and redox-economical manner with
      broad substrate scope under mild reaction conditions. Notably, high regio-, chemo
      , and diasteroselectivity are observed. Mechanistic studies indicate that a
      radical pathway can account for the unusual regioselectivity.

PMID- 29024350
TI  - Epidemiology, pathophysiology and clinical outcomes for heart failure patients
      with a mid-range ejection fraction.
AB  - AIMS: Heart failure (HF) patients with a mid-range ejection fraction (HFmrEF) are
      not well characterized. Accordingly, we examined the epidemiology,
      pathophysiology and clinical outcomes of HF patients with a left ventricular
      ejection fraction (LVEF) of 40-50%. METHODS AND RESULTS: We identified 168
      patients with an LVEF between 40-50% at enrollment into a HF registry, and
      determined whether LVEF was improved, worsened, or the same compared to a prior
      LVEF. Three subgroups of HFmrEF patients were identified: HFmrEF improved (prior
      LVEF <40%); HFmrEF deteriorated (prior LVEF >50%); HFmrEF unchanged (prior LVEF
      40-50%). The majority of patients (73%) were HFmrEF improved, 17% were HFmrEF
      deteriorated, and 10% were HFmrEF unchanged. The demographics of the HFmrEF
      cohort were heterogeneous, with more coronary artery disease in the HFmrEF
      improved group and more hypertension and diastolic dysfunction in the HFmrEF
      deteriorated group. HFmrEF improved patients had significantly (P<0.001) better
      clinical outcomes relative to matched patients with HF and reduced ejection
      fraction, and significantly (P<0.01) improved clinical outcomes relative to
      HFmrEF deteriorated patients, whereas clinical outcomes of the HFmrEF
      deteriorated subgroup of patients were not significantly different from matched
      HF patients with preserved ejection fraction. CONCLUSIONS: Patients with a mid
      range LVEF are heterogeneous. Obtaining historical information with regard to
      prior LVEF allows one to identify a distinct pathophysiological substrate and
      clinical course for HFmrEF patients. Viewed together, these results suggest that
      in the modern era of HF therapeutics, the use of LVEF to categorize the
      pathophysiology of HF may be misleading, and argue for establishing a new
      taxonomy for classifying HF patients.

PMID- 29024351
TI  - What Are Women Told When Requesting Family Planning Services at Clinics
      Associated with Catholic Hospitals? A Mystery Caller Study.
AB  - CONTEXT: Catholic Church directives restrict family planning service provision at
      Catholic health care institutions. It is unclear whether obstetrics and
      gynecology clinics that are owned by or have business affiliations with Catholic
      hospitals offer family planning appointments. METHODS: Mystery callers phoned 144
      clinics nationwide that were found on Catholic hospital websites between December
      2014 and February 2016, and requested appointments for birth control generally,
      copper IUD services specifically, tubal ligation and abortion. Chi-square and
      Fisher's exact tests assessed potential correlates of appointment availability,
      and multivariable logistic regressions were computed if bivariate testing
      suggested multiple correlates. RESULTS: Although 95% of clinics would schedule
      birth control appointments, smaller proportions would schedule appointments for
      copper IUDs (68%) or tubal ligation (58%); only 2% would schedule an abortion.
      Smaller proportions of Catholic-owned than of Catholic-affiliated clinics would
      schedule appointments for birth control (84% vs. 100%), copper IUDs (4% vs. 97%)
      and tubal ligation (29% vs. 72%); for birth control and copper IUD services, no
      other clinic characteristics were related to appointment availability.
      Multivariable analysis confirmed that tubal ligation appointments were less
      likely to be offered at Catholic-owned than at Catholic-affiliated clinics (odds
      ratio. 0.1); location and association with one of the top 10 Catholic health care
      systems also were significant. CONCLUSIONS: Adherence to church directives is
      inconsistent at Catholic-associated clinics. Women visiting such clinics who want
      highly effective methods may need to rely on less effective methods or delay
      method uptake while seeking services elsewhere.

PMID- 29024352
TI  - Characterization of the Conjugation Pattern in Large Polysaccharide-Protein
      Conjugates by NMR Spectroscopy.
AB  - Carbohydrate-based vaccines are among the safest and most effective vaccines and
      represent potent tools for prevention of life-threatening bacterial infectious
      diseases, like meningitis and pneumonia. The chemical conjugation of a weak
      antigen to protein as a source of T-cell epitopes generates a glycoconjugate
      vaccine that results more immunogenic. Several methods have been used so far to
      characterize the resulting polysaccharide-protein conjugates. However, a reduced
      number of methodologies has been proposed for measuring the degree of saccharide
      conjugation at the possible protein sites. Here we show that detailed information
      on large proteins conjugated with large polysaccharides can be achieved by a
      combination of solution and solid-state NMR spectroscopy. As a test case, a large
      protein assembly, l-asparaginase II, has been conjugated with Neisseria
      meningitidis serogroup C capsular polysaccharide and the pattern and degree of
      conjugation were determined.

PMID- 29024353
TI  - Exercise and physical activity for patients with end-stage liver disease:
      Improving functional status and sarcopenia while on the transplant waiting list.
AB  - Sarcopenia and physical deconditioning are frequent complications in patients
      with cirrhosis and end-stage liver disease (ESLD). They are the end result of
      impaired dietary intake, chronic inflammation, altered macronutrient and
      micronutrient metabolism, and low physical activity. Frailty is the end result of
      prolonged sarcopenia and physical deconditioning. It severely affects a patient's
      functional status and presents in approximately 1 in 5 patients on the liver
      transplantation waiting list. Sarcopenia, poor physical fitness/cardiopulmonary
      endurance (CPE), and frailty are all associated with increased mortality in ESLD.
      Clinical trials addressing the usefulness of exercise in patients with cirrhosis
      have shown that it improves the metabolic syndrome, sarcopenia, CPE, health
      related quality of life, and hepatic venous pressure gradient. Although evidence
      on the benefits of exercise on clinical outcomes derived from large clinical
      trials is still missing, based on existing literature from multiple medical
      subspecialties, we believe that an exercise program coupled to a tailored
      nutritional intervention benefits both cardiopulmonary and musculoskeletal
      functions, ultimately translating into improved functional status, sense of well
      being, and possibly less complications from portal hypertension. In conclusion,
      although supervised exercise training is the prevailing approach to manage ESLD
      patients, such intervention is not sustainable or feasible for most patients.
      Innovative home-based physical activity interventions may be able to effectively
      reach a larger number of patients. Liver Transplantation 24 122-139 2018 AASLD.

PMID- 29024354
TI  - Cyclodextrin-Based Formulations: A Non-Invasive Platform for Targeted Drug
      Delivery.
AB  - Cyclodextrins (CDs) are recognized as promising pharmaceutical excipients due to
      their unique ability to form water-soluble inclusion complexes with various
      poorly soluble compounds. The numerous investigations on CDs and their use in
      nanomedicine have received considerable attention in the last three decades,
      leading to the rapid development of new CD-containing formulations that
      significantly facilitate targeted drug delivery and controlled drug release, with
      consequent improvements in drug bioavailability. This MiniReview highlights the
      efficacy and recent uses of CDs for non-invasive drug delivery. Using ophthalmic
      and nasal drug delivery as examples, an overview of chemical properties,
      mechanisms of CDs on drug solubilization, stabilization and permeation, along
      with their toxicological profiles relevant to nasal and ocular administration,
      are provided and discussed. The recent development and application of CD-based
      nanocarrier systems for targeted drug delivery are summarized.

PMID- 29024355
TI  - Genetic testing of individuals with pre-senile cataract identifies patients with
      myotonic dystrophy type 2.

PMID- 29024357
TI  - Transcranial direct current stimulation in stroke rehabilitation: ready to move
      to randomized clinical trials and clinical practice? The issue of safety
      guidelines.

PMID- 29024358
TI  - Comment on 'Acute flaccid myelitis in childhood: a retrospective cohort study'.

PMID- 29024359
TI  - Paravalvular leak closure under intracardiac echocardiographic guidance.
AB  - OBJECTIVES: The objective of this study was to determine the safety and efficacy
      of intracardiac echocardiography (ICE) to guide percutaneous paravalvular leak
      (PVL) closure. BACKGROUND: PVL following surgical valve replacement occurs in 2%
      15% of patients. Percutaneous treatment is an accepted management strategy in
      patients deemed to be too high risk for redo surgery. This is most commonly
      performed with transesophageal (TOE) guidance requiring general anesthesia that
      both potentially further increase the risk of intervention. ICE can be used to
      guide intervention, facilitating procedures to be performed under local
      anesthesia without esophageal intubation potentially making procedures shorter
      and safer and further enabling the treatment of patients that may have been
      turned down for intervention. METHODS: All patients that underwent ICE-guided
      percutaneous transcatheter PVL closure between 2006 and 2016 at the John
      Radcliffe Hospital, Oxford, United Kingdom were retrospectively analyzed.
      RESULTS: Twenty-one procedures were performed in 18 patients during the study
      period. Fourteen patients (77.8%) underwent successful ICE guided PVL closure.
      There were no ICE-related complications. Eleven patients (78.6%) reported
      symptomatic improvement of at least one New York Heart Association (NYHA) Class
      and the remaining 3 patients had no change. No patient demonstrated objective
      evidence of persistent hemolysis following successful closure. There was one
      death within 30 days of the procedure and 1 year survival was 71.4%. CONCLUSIONS:
      Percutaneous paravalvular leak closure guided by ICE without the requirement of
      general anesthesia is feasible, safe, and associated with acceptable procedural
      success rates.

PMID- 29024360
TI  - Synthesis of carbon-based quantum dots from starch extracts: Optical
      investigations.
AB  - Carbon-based quantum dots (C-QDs) were synthesized through microwave-assisted
      carbonization of an aqueous starch suspension mediated by sulphuric and
      phosphoric acids. The as-prepared C-QDs showed blue, green and yellow
      luminescence without the addition of any surface-passivating agent. The C-QDs
      were further analyzed by UV-vis spectroscopy to measure the optical response of
      the organic compound. The energy gaps revealed narrow sizing of C-QDs in the
      semiconductor range. The optical refractive index and dielectric constant were
      investigated. The C-QDs size distribution was characterized. The results
      suggested an easy route to the large scale production of C-QDs materials.

PMID- 29024361
TI  - Emotional processing in obesity: a systematic review and exploratory meta
      analysis.
AB  - The role of emotional functioning in the development and maintenance of obesity
      has been investigated, but the literature is poorly integrated. A systematic
      review and meta-analysis was performed to explore emotional processing
      impairments in obesity. PubMed, Web of Knowledge and PsycINFO databases were
      searched in March 2016, yielding 31 studies comparing emotional processing
      competencies in individuals with obesity, with or without binge eating disorder
      (BED), and control groups. Meta-analyses demonstrated that individuals with
      obesity had higher scores of alexithymia (d = 0.53), difficulty in identifying
      feelings (d = 0.34) and externally oriented thinking style (d = 0.31), when
      compared with control groups. On other competencies, patients with obesity,
      especially those with comorbid BED, reported lower levels of emotional awareness
      and difficulty in using emotion regulation strategies, namely, reduced cognitive
      reappraisal and acceptance, and greater suppression of expression. No evidence of
      impaired ability to recognize emotions in others or verbally express emotions was
      found. A general emotion-processing deficit in obesity was not supported.
      Instead, an emotional avoidance style may occur modulating later responses of
      emotion regulation. Additional research is needed to extend the comprehension of
      these conclusions and the role of BED in emotional functioning in obesity.

PMID- 29024362
TI  - The Impact of Entrepreneurial Leadership on Nurses' Innovation Behavior.
AB  - PURPOSE: The purpose of this study was to examine the influence of
      entrepreneurial leadership on nurses' innovation work behavior and its
      dimensions. DESIGN AND METHODS: This cross-sectional study employed the 10-item
      Innovation Work Behavior Questionnaire and the 8-item Entrepreneurial Leadership
      Questionnaire to explore the impact of entrepreneurial leadership on the
      innovation work behavior of 273 nurses from public and private hospitals in Iran.
      FINDINGS: Entrepreneurial leadership had a significant positive impact on nurses'
      innovation work behavior and most strongly improved idea exploration, followed by
      idea generation, idea implementation, and idea championing. CONCLUSIONS:
      Entrepreneurial leadership was effective in enhancing nurses' innovation work
      behavior. More attention needs to be focused on developing entrepreneurial
      leadership competencies and on developing nurse leaders. CLINICAL RELEVANCE:
      Healthcare policies and strategies are needed to facilitate the implementation of
      entrepreneurial leadership by providing healthcare leaders with the appropriate
      environment.

PMID- 29024363
TI  - Prevalence, predictors and correlates of insomnia in US army soldiers.
AB  - The objective of this study was to investigate the rates, predictors and
      correlates of insomnia in a national sample of US Army soldiers. Data were
      gathered from the cross-sectional survey responses of the All-Army Study, of the
      Army Study to Assess Risk and Resilience in Service members. Participants were a
      representative sample of 21 499 US Army soldiers who responded to the All-Army
      Study self-administered questionnaire between 2011 and 2013. Insomnia was defined
      by selected DSM-5 criteria using the Brief Insomnia Questionnaire. The results
      highlight significant functional difficulties associated with insomnia among US
      soldiers, as well as insights into predictors of insomnia specific to this
      population. Insomnia was present in 22.76% of the sample. Predictors of insomnia
      status in logistic regression included greater number of current mental health
      disorders, less perceived open lines of communication with leadership, less unit
      member support and less education. Insomnia had global, negative associations
      with health, social functioning, support, morale, work performance and Army
      career intentions. The results provide the strongest evidence to-date that
      insomnia is common in a military population, and is associated with a wide array
      of negative factors in the domains of health, military readiness and intentions
      to remain in military careers.

PMID- 29024364
TI  - Healthcare utilization after liver transplantation is highly variable among both
      centers and recipients.
AB  - The relationship between healthcare utilization before and after liver
      transplantation (LT), and its association with center characteristics, is
      incompletely understood. This was a retrospective cohort study of 34 402 adult
      LTs between 2002 and 2013 using Vizient inpatient claims data linked to the
      United Network for Organ Sharing (UNOS) database. Multivariable mixed-effects
      linear regression models evaluated the association between hospitalization 90
      days pre-LT and the number of days alive and out of the hospital (DAOH) 1 year
      post-LT. Of those patients alive at LT discharge, 24.7% spent >=30 days
      hospitalized during the first year. Hospitalization in the 90 days pre-LT was
      inversely associated with DAOH (beta = -3.4 DAOH/week hospitalized pre-LT; P =
      .002). Centers with >30% of their liver transplant recipients hospitalized >=30
      days in the first LT year were typically smaller volume and/or transplanting
      higher risk recipients (Model for End-Stage Liver Disease [MELD] score >=35,
      inpatient or ventilated pre-LT). In conclusion, pre-LT hospitalization predicts 1
      year post-LT hospitalization independent of MELD score at the patient-level,
      whereas center-specific post-LT healthcare utilization is associated with certain
      center behaviors and selection practices.

PMID- 29024366
TI  - Tethyan changes shaped aquatic diversification.
AB  - The Tethys Ocean existed between the continents of Gondwana and Laurasia from the
      Triassic to the Pliocene. Analyses of multiple biogeographic and phylogenetic
      histories reveal that the subsequent breakup of the Tethys greatly influenced the
      distributions of many species. The ancestral Tethyan realm broke into five
      biogeographic provinces, including the present-day East Pacific, West Atlantic,
      East Atlantic, Mediterranean Sea, and Indo-West Pacific. Palaeogeographic maps
      illustrate the Mesozoic Atlantic opening, the Cenozoic closure of the Tethys, the
      Messinian Salinity Crisis, the mid-Miocene closure of the Central American
      Seaway, and Quaternary geological changes. Further, we consider Cenozoic sea
      level changes and the formation of freshwater habitats. These reconstructions
      allow assessment of patterns of aquatic diversification for marine and freshwater
      animals, and comparison of vicariance and dispersal processes. Estimated
      divergence times indicate that fragmentation of the Tethys was responsible for
      the vicariant speciation of aquatic animals because these dates are consistent
      with associated tectonic events. The opening of the Atlantic Ocean during the
      Cretaceous is responsible for the earliest isolation between the West and East
      Atlantic. The mid-Miocene closure of the Tethys, which blocked global equatorial
      currents, appears to have isolated the Atlantic/Mediterranean Sea and Indo-West
      Pacific. Finally, formation of the Isthmus of Panama isolated East Pacific and
      West Atlantic marine organisms. Dispersals related to the Messinian Salinity
      Crisis and Quaternary sea-level changes influenced population structuring.
      Tethyan changes affected marine habitats, created new freshwater habitats, inland
      caves and ancient lakes along the Alps and Himalayas, and influenced anchialine
      caves at the edge of the ancient sea. The extensive new habitats provided
      opportunities for colonisation and rapid diversification. Future work should
      focus on testing the biological impact of the series of Tethyan changes.

PMID- 29024365
TI  - Non-target site SDHI resistance is present as standing genetic variation in field
      populations of Zymoseptoria tritici.
AB  - BACKGROUND: A new generation of more active succinate dehydrogenase (Sdh)
      inhibitors (SDHIs) is currently widely used to control Septoria leaf blotch in
      northwest Europe. Detailed studies were conducted on Zymoseptoria tritici field
      isolates with reduced sensitivity to fluopyram and isofetamid; SDHIs which have
      only just or not been introduced for cereal disease control, respectively.
      RESULTS: Strong cross-resistance between fluopyram and isofetamid, but not with
      other SDHIs, was confirmed through sensitivity tests using laboratory mutants and
      field isolates with and without Sdh mutations. The sensitivity profiles of most
      field isolates resistant to fluopyram and isofetamid were very similar to a lab
      mutant carrying SdhC-A84V, but no alterations were found in SdhB, C and D.
      Inhibition of mitochondrial Sdh enzyme activity and control efficacy in planta
      for those isolates was severely impaired by fluopyram and isofetamid, but not by
      bixafen. Isolates with similar phenotypes were not only detected in northwest
      Europe but also in New Zealand before the widely use of SDHIs. CONCLUSION: This
      is the first report of SDHI-specific non-target site resistance in Z. tritici.
      Monitoring studies show that this resistance mechanism is present and can be
      selected from standing genetic variation in field populations. (c) 2017 The
      Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of
      Society of Chemical Industry.

PMID- 29024367
TI  - Commissioning guidance for weight assessment and management in adults and
      children with severe complex obesity.
AB  - The challenge of managing the epidemic of patients with severe and complex
      obesity disease in secondary care is largely unmet. In England, the National
      Institute of Health and Care Excellence and the National Health Service England
      have published guidance on the provision of specialist (non-surgical) weight
      management services. We have undertaken a systematic review of 'what evidence
      exists for what should happen in/commissioning of: primary or secondary care
      weight assessment and management clinics in patients needing specialist care for
      severe and complex obesity?' using an accredited methodology to produce a model
      for organization of multidisciplinary team clinics that could be developed in
      every healthcare system, as an update to a previous review. Additions to the
      previous guidance were multidisciplinary team pathways for children/adolescent
      patients and their transition to adult care, anaesthetic assessment and
      recommendations for ongoing shared care with general practitioners, as a chronic
      disease management pathway.

PMID- 29024369
TI  - Facile Supramolecular Processing of Carbon Nanotubes and Polymers for
      Electromechanical Sensors.
AB  - We herein report a facile, cost-competitive, and scalable method for producing
      viscoelastic conductors via one-pot melt-blending using polymers and
      supramolecular gels composed of carbon nanotubes (CNTs), diphenylamine (DP), and
      benzophenone (BP). When mixed, a non-volatile eutectic liquid (EL) produced by
      simply blending DP with BP (1:1 molar ratio) enabled not only the gelation of
      CNTs (EL-CNTs) but also the dissolution of a number of commodity polymers. To
      make use of these advantages, viscoelastic conductors were produced via one-pot
      melt-blending the EL and CNTs with a model thermoplastic elastomer, poly(styrene
      b-butadiene-b-styrene) (SBS, styrene 30 wt %). The resulting composites displayed
      an excellent electromechanical sensory along with re-mendable properties. This
      simple method using cost-competitive EL components is expected to provide an
      alternative to the use of expensive ionic liquids as well as to facilitate the
      fabrication of novel composites for various purposes.

PMID- 29024368
TI  - Measuring the effectiveness of management interventions at regional scales by
      integrating ecological monitoring and modelling.
AB  - BACKGROUND: Because of site-specific effects and outcomes, it is often difficult
      to know whether a management strategy for the control of pests has worked or not.
      Population dynamics of pests are typically spatially and temporally variable.
      Moreover, interventions at the scale of individual fields or farms are
      essentially unreplicated experiments; a decrease in a target population following
      management cannot safely be interpreted as success because, for example, it might
      simply be a poor year for that species. Here, we argue that if large-scale data
      are available, population models can be used to measure outcomes against the
      prevailing mean and variance. We apply this approach to the problem of rotational
      management of the weed Alopecurus myosuroides. RESULTS: We derived density
      structured population models for a set of fields that were not subject to
      rotational management (continuous winter wheat) and another group that were
      (rotated into spring barley to control A. myosuroides). We used these models to
      construct means and variances of the outcomes of management for given starting
      conditions, and to conduct transient growth analysis. We show that, overall, this
      management strategy is successful in reducing densities of weeds, albeit with
      considerable variance. However, we also show that one variant (rotation to spring
      barley along with variable sowing) shows little evidence for additional control.
      CONCLUSION: Our results suggest that rotational strategies can be effective in
      the control of this weed, but also that strategies require careful evaluation
      against a background of spatiotemporal variation. (c) 2017 The Authors. Pest
      Management Science published by John Wiley & Sons Ltd on behalf of Society of
      Chemical Industry.

PMID- 29024370
TI  - Classification of Heat-Related Illness Symptoms Among Florida Farmworkers.
AB  - BACKGROUND: Farmworkers working in hot and humid environments have an increased
      risk for heat-related illness (HRI) if their thermoregulatory capabilities are
      overwhelmed. The manifestation of heat-related symptoms can escalate into life
      threatening events. Increasing ambient air temperatures resulting from climate
      change will only exacerbate HRI in vulnerable populations. We characterize HRI
      symptoms experienced by farmworkers in three Florida communities. METHODS: A
      total of 198 farmworkers enrolled in 2015-2016 were asked to recall if they
      experienced seven HRI symptoms during the previous work week. Multivariable
      logistic regression was used to estimate odds ratios (ORs) and 95% confidence
      intervals (CIs) for the association between selected sociodemographic
      characteristics and reporting three or more symptoms. Latent class analysis was
      used to identify classes of symptoms representing the HRI severity range. We
      examined sociodemographic characteristics of the farmworkers across the latent
      classes. RESULTS: The mean age (+/-SD) of farmworkers was 38.0 (+/-8) years; the
      majority were female (60%) and Hispanic (86%). Most frequently reported symptoms
      were heavy sweating (66%), headache (58%), dizziness (32%), and muscle cramps
      (30%). Females had three times the odds of experiencing three or more symptoms
      (OR = 2.86, 95% CI 1.18-6.89). Symptoms fell into three latent classes, which
      included mild (heavy sweating; class probability = 54%), moderate (heavy
      sweating, headache, nausea, and dizziness; class probability = 24%), and severe
      (heavy sweating, headache, nausea, dizziness, muscle cramps; class probability =
      22%). CONCLUSIONS: Farmworkers reported a high burden of HRI symptoms that appear
      to cluster in physiologic patterns. Unrecognized accumulation of symptoms can
      escalate into life-threatening situations if untreated. Our research can inform
      interventions to promote early recognition of HRI, on-site care, and appropriate
      occupational health policy. Administrative or engineering workplace controls may
      also reduce the manifestation of HRI. CLINICAL RELEVANCE: This study advances the
      current knowledge of HRI symptoms in farmworkers and moves beyond reporting
      individual symptoms by utilizing latent class analysis to identify how symptoms
      tend to co-occur together in this population. It acknowledges multiple symptoms
      occurring as a result of occupational heat exposure and highlights the importance
      of symptom recognition.

PMID- 29024372
TI  - Feedback Kinetics in Mechanochemistry: The Importance of Cohesive States.
AB  - Although mechanochemical synthesis is becoming more widely applied and even
      commercialised, greater basic understanding is needed if the field is to progress
      on less of a trial-and-error basis. We report that a mechanochemical reaction in
      a ball mill exhibits unusual sigmoidal feedback kinetics that differ dramatically
      from the simple first-order kinetics for the same reaction in solution. An
      induction period is followed by a rapid increase in reaction rate before the rate
      decreases again as the reaction goes to completion. The origin of these unusual
      kinetics is found to be a feedback cycle involving both chemical and mechanical
      factors. During the reaction the physical form of the reaction mixture changes
      from a powder to a cohesive rubber-like state, and this results in the observed
      reaction rate increase. The study reveals that non-obvious and dynamic
      rheological changes in the reaction mixture must be appreciated to understand how
      mechanochemical reactions progress.

PMID- 29024371
TI  - Understanding parent-teacher agreement of the Strengths and Difficulties
      Questionnaire (SDQ): Comparison across seven European countries.
AB  - Assessments of child psychopathology are often derived from parental and teacher
      reports, yet there is substantial disagreement. This study utilized data from 7
      European countries to examine parent-teacher agreement and possible explanatory
      factors for parent-teacher disagreement such as child and family characteristics,
      parenting dimensions, and maternal distress were explored. Parent-teacher
      agreement of the Strengths and Difficulties Questionnaire were assessed using a
      cross-sectional survey of 4,894 school aged children 6-11 from the School
      Children Mental Health Europe Project. Parent-teacher agreement was low to
      moderate (Pearson correlation ranging from .24 (Prosocial) to .48 (Hyperactivity)
      for the 5 subscales across 7 countries); kappa coefficient ranged from .01
      (Turkey) to .44 (Italy) for internalizing problems and .19(Romania) to .44(Italy)
      for externalizing problems. Child's gender and age, mother's employment status,
      single parent home, number of children in household, and selected parenting
      dimension were found to be explanatory of informant disagreement. This study not
      only serves to advance our understanding of parent-teacher agreement of the
      Strengths and Difficulties Questionnaire in 7 European countries but provides a
      novel approach to examining the factors that contribute to informant
      disagreement.

PMID- 29024373
TI  - Pulmonary vascular disease due to left heart disease: how to achieve a more
      accurate approach beyond the haemodynamic phenotype: reply.

PMID- 29024375
TI  - Artificial urine and FBS supplemented media in cytocompatibility assays for PLGA
      PEG-based intravesical devices using the urothelium cell line UROtsa.
AB  - European and German directives for approval of new medical devices require tests
      for cytotoxicity in relevant media, since urine can influence cytotoxicity of
      biodegradable devices. The aim of this study was to determine the long-term
      cytotoxicity of PLGA-b-mPEG (PLGA-PEG) polymer carriers and artificial urine (AU)
      to human UROtsa cells. Benign urothelial UROtsa cells were incubated in fetal
      bovine serum-containing RPMI 1640 medium supplemented with a range of
      concentrations of AU for 24 h and 7 days. Cell viability was determined by the
      XTT assay and by live/dead staining. The cytotoxicity of medium containing
      degradation products from PLGA-PEG carriers was also tested on the UROtsa cells
      in AU-containing and control medium. PLGA-PEG carriers exhibited no cytotoxicity
      to UROtsa cells after 24 h of incubation. However, after 7 days, cytotoxicity was
      observed, but this was largely attributable to the effects of 30% AU on the
      cells. Compared to phosphate buffer saline (PBS) and normalized to RPMI 1640
      medium, significant cytotoxicity was observed by 24 h in medium containing 50% AU
      and by 7 days in medium containing 30% AU. Live/Dead staining confirmed
      proliferation results and no pH-changes could be observed. Here we demonstrate
      for the first time the impact of AU on standard cytotoxicity tests related to
      biomaterials for urinary-tract applications. Our study showed cytotoxic effects
      of high concentrations of 50% AU by 24 h and by physiological concentrations of
      AU (i.e., 30%) by 7 days. We have also demonstrated that PLGA-PEG has no
      cytotoxic effects in the appropriate AU-containing test environment. (c) 2017
      Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2140
      2147, 2018.

PMID- 29024376
TI  - Evaluation of collagen foam, poly(l-lactic acid) nanofiber mesh, and
      decellularized matrices for corneal regeneration.
AB  - Corneal tissue engineering efforts to obtain corneal tissue matrices through
      various types of materials for the replacement of damaged tissues. In this study,
      three different corneal constructs were prepared and evaluated in terms of
      morphological, optical, and biological characteristics. Type-I collagen was used
      to obtain collagen foam scaffolds through dehydrothermal crosslinking, while
      poly(l-lactic acid) (PLLA) was used to produce both random and aligned oriented
      electrospun corneal constructs. Bovine corneas were decellularized as third
      matrix. Software analyses showed that average pore size of collagen scaffolds was
      88.207 +/- 29.7 um, while the average fiber diameter of aligned and random PLLA
      scaffolds were 0.69 +/- 0.03 and 0.65 +/- 0.03 MUm, respectively. Degradation
      profiles revealed that collagen foam exhibits high degradation (20% mass loss)
      while electrospun PLLA scaffolds hold low degradation (9% mass loss) rates at day
      28. Transmittance values of the obtained scaffolds were calculated as 92, 80, and
      70% for collagen, PLLA, and decellularized cornea constructs, respectively. The
      evaluation of stromal keratocyte behavior on the constructs revealed that the
      cells exhibited their own morphology mostly on the aligned PLLA constructs, while
      they were mostly active on random PLLA electrospun corneal scaffolds. (c) 2017
      Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2157
      2168, 2018.

PMID- 29024377
TI  - Forcing Ladderenes into Plastic Semiconductors with Mechanochemistry.
AB  - May the force be with you: Xia, Burns, Martinez, and co-workers harnessed the
      ring strain of ladderenes to enable both their polymerization and mechanochemical
      unzipping to yield semiconducting polyacetylene-based block copolymers. These
      materials have promise as functional polymers for applications such as detection
      of physical stress.

PMID- 29024374
TI  - Human papillomavirus and posttransplantation cutaneous squamous cell carcinoma: A
      multicenter, prospective cohort study.
AB  - Organ transplant recipients (OTRs) have a 100-fold increased risk of cutaneous
      squamous cell carcinoma (cSCC). We prospectively evaluated the association
      between beta genus human papillomaviruses (betaPV) and keratinocyte carcinoma in
      OTRs. Two OTR cohorts without cSCC were assembled: cohort 1 was transplanted in
      2003-2006 (n = 274) and cohort 2 was transplanted in 1986-2002 (n = 352).
      Participants were followed until death or cessation of follow-up in 2016. betaPV
      infection was assessed in eyebrow hair by using polymerase chain reaction-based
      methods. betaPV IgG seroresponses were determined with multiplex serology. A
      competing risk model with delayed entry was used to estimate cumulative incidence
      of histologically proven cSCC and the effect of betaPV by using a multivariable
      Cox regression model. Results are reported as adjusted hazard ratios (HRs). OTRs
      with 5 or more different betaPV types in eyebrow hair had 1.7 times the risk of
      cSCC vs OTRs with 0 to 4 different types (HR 1.7, 95% confidence interval 1.1
      2.6). A similar risk was seen with high betaPV loads (HR 1.8, 95% confidence
      interval 1.2-2.8). No significant associations were seen between serum antibodies
      and cSCC or between betaPV and basal cell carcinoma. The diversity and load of
      betaPV types in eyebrow hair are associated with cSCC risk in OTRs, providing
      evidence that betaPV is associated with cSCC carcinogenesis and may present a
      target for future preventive strategies.

PMID- 29024378
TI  - The CYCLOCALYX study: Ovulatory cycle affects circulating compartments of the
      endothelial glycocalyx in blood.
AB  - PROBLEM: The endothelial glycocalyx (EGX) plays an important role in vascular
      integrity. Recently, increased levels of EGX components were detected in the
      circulating blood of healthy pregnant women and were related to the increased
      tendency to edema formation during gestation. However, the EGX has not yet been
      systematically studied in non-pregnant women during ovulatory cycles. METHOD OF
      STUDY: Serum levels of EGX components syndecan-1, heparan sulfate, and hyaluronan
      in healthy women (n = 16) at 3 phases of the ovulatory cycle (early follicular
      phase, at ovulation, and mid-luteal phase) were compared with a control group of
      healthy men (n = 10). Using immunofluorescence microscopy in cultured human
      umbilical vein endothelial cells, the effects of progesterone and estrogen on the
      EGX were measured. RESULTS: Syndecan-1 increased from 11.1 +/- 2.4 ng/mL at
      ovulation to 12.6 +/- 2.3 ng/mL in mid-luteal phase (P = .031) and of heparan
      sulfate from 663 +/- 35 ng/mL to 782 +/- 55 ng/mL (P = .011). In contrast to
      estrogen, there was a detrimental effect of progesterone on the EGX in HUVECs.
      CONCLUSION: The relationship between the natural menstrual cycle and the EGX as
      an indicator of vascular permeability may provide a new explanation for
      premenstrual edema in healthy women. This may be an attendant phenomenon of a
      regular physiological process, the hormonal downregulation of the vascular
      barrier during pregnancy.

PMID- 29024379
TI  - Can a renal nurse assess fluid status using ultrasound on the inferior vena cava?
      A cross-sectional interrater study.
AB  - INTRODUCTION: Ultrasound of the inferior vena cava (IVC-US) has been used to
      estimate intravascular volume status and fluid removal during a hemodialysis
      session. Usually, renal nurses rely on other, imprecise methods to determine
      ultrafiltration. To date, no study has examined whether renal nurses can reliably
      perform ultrasound for volume assessment and for potential prevention of
      intradialytic hypotension. This pilot study aimed to determine if a renal nurse
      could master the skill of performing and correctly interpreting Point of Care
      Ultrasound on patients receiving hemodialysis. METHODS: After receiving
      theoretical training and performing 100 training scans, a renal nurse performed
      60 ultrasound scans on 10 patients. These were categorized by the nurse into
      hypovolemic, euvolemic, or hypervolemic through measurement of the maximal
      diameter and degree of collapse of the IVC. Scans were subsequently assessed for
      adequacy and quality by two sonologists, who were blinded to each other's and the
      nurse's results. FINDINGS: The interrater reliability of 60 scans was good, with
      intraclass correlation 0.79 (95% confidence interval (CI) =0.63-0.87) and with a
      good interrater agreement for the following estimation of intravascular volume
      (Cohen's weighted Kappa kappaw  = 0.62), when comparing the nurse to an expert
      sonographer. DISCUSSION: A renal nurse can reliably perform ultrasound of the IVC
      in hemodialysis patients, obtaining high quality scans for volume assessment of
      hemodialysis patients. This novel approach could be more routinely applied by
      other renal nurses to obtain objective measures of patient volume status in the
      dialysis setting.

PMID- 29024381
TI  - An integrated community-based outpatient therapeutic feeding programme for severe
      acute malnutrition in rural Southern Ethiopia: Recovery, fatality, and
      nutritional status after discharge.
AB  - A scaled up and integrated outpatient therapeutic feeding programme (OTP) brings
      the treatment of severely malnourished children closer to the community. This
      study assessed recovery from severe acute malnutrition (SAM), fatality, and acute
      malnutrition up to 14 weeks after admission to a programme integrated in the
      primary health care system. In this cohort study, 1,048 children admitted to 94
      OTPs in Southern Ethiopia were followed for 14 weeks. Independent anthropometric
      measurements and information on treatment outcome were collected at four home
      visits. Only 32.7% (248/759) of children with SAM on admission fulfilled the
      programme recovery criteria at the time of discharge (i.e., gained 15% in weight,
      or oedema, if present at admission, was resolved at discharge). Of all children
      admitted to the programme for whom nutritional assessment was done 14 weeks
      later, 34.6% (321/928) were severely malnourished, and 37.5% (348/928) were
      moderately malnourished; thus, 72.1% were acutely malnourished. Of the children,
      27/982 (2.7%) had died by 14 weeks, of whom all but one had SAM on admission.
      Children with severe oedema on admission had the highest fatality rate (12.0%,
      9/75). The median length of admission to the programme was 6.6 weeks
      (interquartile range: 5.3, 8.4 weeks). Despite children participating for the
      recommended duration of the programme, many children with SAM were discharged
      still acutely malnourished and without reaching programme criteria for recovery.
      For better outcome of OTP, constraints in service provision by the health system
      as well as challenges of service utilization by the beneficiaries should be
      identified and addressed.

PMID- 29024382
TI  - Comparison of outcomes with surgical cut-down versus percutaneous transfemoral
      transcatheter aortic valve replacement: TAVR transfemoral access comparisons
      between surgical cut-down and percutaneous approach.
AB  - OBJECTIVES: The objective is to compare the short-term (30 days) and late (12
      months) vascular adverse events in patients undergoing transfemoral (TF)
      transcatheter aortic valve replacement (TAVR) by surgical cut-down (SC) vs.
      percutaneous (PC) approaches. BACKGROUND: Programs continue to utilize both
      approaches in TF-TAVR. There are limited data comparing outcomes by SC vs. PC
      approaches and long-term effects of endovascular intervention facilitated
      hemostasis on late vascular adverse events. METHODS: A total of 146 men and women
      aged 79.7 +/- 10.0 years with severe aortic stenosis deemed extreme or high risk
      for surgery underwent TAVR via TF access. 61 had SC and 85 had PC approaches.
      Valve Academic Research Consortium (VARC-2) outcomes were assessed at an average
      of 12.1 months after TAVR. RESULTS: Hospital length of stay (LOS) post-TAVR was
      shorter for the PC group compared to the SC group (5.1 +/- 3.9 vs. 8.2 +/- 6.6
      days; P < 0.001). More patients were discharged directly to home in the PC than
      the SC group (85.9% vs. 68.9%, P < 0.05). At 30 days, there were 13/61 (21.3%)
      and 16/85 (18.8%; P < 0.05) of any vascular events, and 2/61 (3.3%) and 2/85
      (2.4%; P = 0.73) major vascular events in the SC and PC groups, respectively.
      There was no difference in all-cause mortality between the SC (14/61; 23%) and PC
      groups [17/85 (20%); P = 0.34]. There was no difference in any [4/33 (12%) vs.
      3/43 (7%); P = 0.84] or major vascular adverse events [1/33 (3%) vs. 1/43 (2%); P
      = 0.79] in subjects that underwent adjunctive endovascular intervention compared
      to those who did not, respectively. There were no statistically significant
      univariate or multivariate predictors of any vascular event at 12 months when
      comparing SC to PC groups. CONCLUSION: For TF TAVR, the PC approach, when
      compared to the SC approach, is associated with a shorter hospital LOS and higher
      rate of direct discharge to home with similar risk of vascular complications,
      late vascular adverse events, and all-cause mortality at 12 months.

PMID- 29024383
TI  - Down-regulation of LncRNA CCAT1 enhances radiosensitivity via regulating miR-148b
      in breast cancer.
AB  - LncRNA colon-cancer-associated transcript-1 (CCAT1) was proved to be a potential
      prognostic biomarker for breast cancer progression. However, the role of CCAT1 in
      regulating radiosensitivity of breast cancer and its underlying mechanism have
      not been investigated. The present study showed that CCAT1 was up-regulated and
      miR-148b was down-regulated in radioresistant breast cancer tissues compared with
      radiosensitive breast cancer tissues. Radiation treatment triggered a significant
      increase in CCAT1 and an obvious decrease in miR-148b. CCAT1 down-regulation
      reduced colony formation rates and caspase3 activity in breast cancer cells under
      irradiation. Moreover, CCAT1 could negatively regulate miR-148b expression.
      Furthermore, overexpression of miR-148b suppressed colony survival fraction and
      caspase3 expression under irradiation in breast cancer cells, which was
      exacerbated by CCAT1 knockdown. Taken together, this study demonstrated that
      CCAT1 down-regulation improved radiosensitivity of breast cancer cells via
      negatively regulating miR-148b expression, providing a crucial clue for lncRNA
      miRNA interaction in the mechanism of radiosensitivity of breast cancer.

PMID- 29024380
TI  - Cell-to-cell communication: microRNAs as hormones.
AB  - Mammalian cells can release different types of extracellular vesicles (EVs),
      including exosomes, microvesicles, and apoptotic bodies. Accumulating evidence
      suggests that EVs play a role in cell-to-cell communication within the tumor
      microenvironment. EVs' components, such as proteins, noncoding RNAs [microRNAs
      (miRNAs), and long noncoding RNAs (lncRNAs)], messenger RNAs (mRNAs), DNA, and
      lipids, can mediate paracrine signaling in the tumor microenvironment. Recently,
      miRNAs encapsulated in secreted EVs have been identified in the extracellular
      space. Mature miRNAs that participate in intercellular communication are released
      from most cells, often within EVs, and disseminate through the extracellular
      fluid to reach remote target cells, including tumor cells, whose phenotypes they
      can influence by regulating mRNA and protein expression either as tumor
      suppressors or as oncogenes, depending on their targets. In this review, we
      discuss the roles of miRNAs in intercellular communication, the biological
      function of extracellular miRNAs, and their potential applications for diagnosis
      and therapeutics. We will give examples of miRNAs that behave as hormones.

PMID- 29024384
TI  - A Hydrogen-Bonded Hexagonal Buckybowl Framework.
AB  - A hydrogen-bonded two-dimensionally networked buckybowl architecture is
      presented. Two types of hexagonal network (HexNet) structures (CPSM-1 and CPSM-2)
      have been achieved based on a sumanene derivative (CPSM) possessing 4,4'
      dicarboxy-o-terphenyl groups in the periphery. CPSM-1 has a waved HexNet
      structure with an alternate alignment of upward and downward bowls. CPSM-2 has a
      bilayered HexNet structure composed of hamburger-shaped dimers of the bowls. This
      demonstrates that non-planar pi-systems can be networked two-dimensionally by an
      appropriate supramolecular synthon to achieve structurally well-defined unique
      bumpy pi-sheets. Furthermore, we revealed that CPSM-2 undergoes anisotropic
      shrinking along the c axis by 11 % under high pressure conditions (970 MPa). The
      shrinkage is brought about by offset sliding between bumpy pi-surfaces of the
      bilayered HexNet sheets.

PMID- 29024385
TI  - Integrin beta-3 is required for the attachment, retention and therapeutic
      benefits of human cardiospheres in myocardial infarction.
AB  - Cardiovascular diseases remain the leading causes of death worldwide. Stem cell
      therapy offers a promising option to regenerate injured myocardium. Among the
      various types of stem cells, cardiosphere cells represent a mixture of intrinsic
      heart stem cells and supporting cells. The safety and efficacy of cardiosphere
      cells have been demonstrated in recent clinical trials. Cell-matrix interaction
      plays an important role in mediating the engraftment of injected stem cells.
      Here, we studied the role of integrin beta-3 in cardiosphere-mediated cell
      therapy in a mouse model of myocardial infarction. Our results indicated that
      inhibiting integrin beta-3 reduced attachment, retention and therapeutic benefits
      of human cardiospheres in mice with acute myocardial infarction. This suggests
      integrin beta-3 plays an important role in cardiosphere-mediated heart
      regeneration.

PMID- 29024386
TI  - Design of 3D Graphene-Oxide Spheres and Their Derived Hierarchical Porous
      Structures for High Performance Supercapacitors.
AB  - Graphene-oxide (GO) based porous structures are highly desirable for
      supercapacitors, as the charge storage and transfer can be enhanced by
      advancement in the synthesis. An effective route is presented of, first,
      synthesis of three-dimensional (3D) assembly of GO sheets in a spherical
      architecture (GOS) by flash-freezing of GO dispersion, and then development of
      hierarchical porous graphene (HPG) networks by facile thermal-shock reduction of
      GOS. This leads to a superior gravimetric specific capacitance of ~306 F g-1 at
      1.0 A g-1 , with a capacitance retention of 93% after 10 000 cycles. The values
      represent a significant capacitance enhancement by 30-50% compared with the GO
      powder equivalent, and are among the highest reported for GO-based structures
      from different chemical reduction routes. Furthermore, a solid-state flexible
      supercapacitor is fabricated by constructing the HPG with polymer gel
      electrolyte, exhibiting an excellent areal specific capacitance of ~220 mF cm-2
      at 1.0 mA cm-2 with exceptional cyclic stability. The work reveals a facile but
      efficient synthesis approach of GO-based materials to enhance the capacitive
      energy storage.

PMID- 29024387
TI  - Ethnic and population differences in the genetic predisposition to human obesity.
AB  - Obesity rates have escalated to the point of a global pandemic with varying
      prevalence across ethnic groups. These differences are partially explained by
      lifestyle factors in addition to genetic predisposition to obesity. This review
      provides a comprehensive examination of the ethnic differences in the genetic
      architecture of obesity. Using examples from evolution, heritability, admixture,
      monogenic and polygenic studies of obesity, we provide explanations for ethnic
      differences in the prevalence of obesity. The debate over definitions of race and
      ethnicity, the advantages and limitations of multi-ethnic studies and future
      directions of research are also discussed. Multi-ethnic studies have great
      potential to provide a better understanding of ethnic differences in the
      prevalence of obesity that may result in more targeted and personalized obesity
      treatments.

PMID- 29024388
TI  - Potential biomarkers in patients with systemic sclerosis.
AB  - AIM: Reduced capillary density is considered the hallmark of systemic sclerosis
      (SSc) leads to tissue hypoxia, a condition that usually induces angiogenesis. The
      objective of our study is to investigate mediators regulating angiogenesis in SSc
      and to correlate their levels with serological and clinical parameters. METHODS:
      vascular endothelial growth factor, fibroblast growth factor-2, endostatin,
      thrombospondin-1 and soluble vascular cell and intracellular adhesion molecules
      (sICAM-1 and sVCAM-1) were measured in sera of SSc and normal subjects by enzyme
      linked immunosorbent assay. RESULTS: Among the pro- and anti-angiogenic
      mediators, endostatin was significantly higher in SSc than in the control
      subjects. Out of the proteases involved in endostatin production, elastase but
      not cathepsin-L, was significantly increased in SSc patients. The soluble
      adhesion molecules sICAM-1 and sVCAM-1 were significantly increased and they
      occur in parallel. sICAM-1, but not sVCAM-1 positively correlates with the
      inflammatory markers C-reactive protein (CRP) and erythrocyte sedimentation rate
      (ESR). CONCLUSIONS: Endostatin, elastase and the soluble adhesion molecules
      (sICAM-1 and sVCAM-1) are potentially involved in the pathogenesis of SSc.
      Moreover, the significant correlation observed between sICAM-1 and CRP and ESR
      indicates that sICAM-1 might be a useful biomarker of the inflammatory state of
      the disease.

PMID- 29024390
TI  - Pollination in the Chilean Mediterranean-type ecosystem: a review of current
      advances and pending tasks.
AB  - We conducted a systematic review of the scientific literature published on plant
      pollinator interactions, from both the plant and pollinator perspective, in the
      Chilean Mediterranean-type ecosystem (MTE hereafter). Our search identified 69
      published papers on 235 native plant species from 62 families. Less than 7.9% of
      the flowering species inhabiting the Chilean Mediterranean have been studied, and
      most studies were restricted to only one locality and one reproductive season.
      The geographic location of the studies differed from a random pattern, showing
      two well-defined areas where most studies were conducted. Likewise, most studies
      in the Andes Range were performed above 2000 m a.s.l. The number of species of
      flower visitor per plant species was low (4.25 +/- 0.22), which probably results
      from the historical and biogeographic isolation of Chile. This literature survey
      shows that studies relating floral traits with pollinator attraction and plant
      reproduction are the most frequent topics of research, reaching 37.6% of studies,
      followed by studies that examine pollination in relation to human impact (16.1%),
      micro- and macroevolution (14.0%), relationships between pollination and other
      ecological interactions (10.8%), community and network assessments (11.8%), and
      effects of abiotic variables on pollination interactions (9.7%). Our review
      highlights a lack of research on the effects of pollination for anthropogenic
      land use especially as agricultural practice is one of the most salient features
      of the Chilean MTE. Future directions to increase our understanding of the role
      of plant-pollinator relationships for biodiversity maintenance should include: to
      extend the taxonomic and geographic scope of research, to increase the number of
      spatial and temporal replicates, to increase the number of studies on pollination
      networks as they provide estimates of community complexity and putative
      stability, to develop studies that estimate the importance of pollination for
      plant demographic parameters and conservation, and to conduct studies that
      estimate the ecological service provided by Chilean native pollinators for crop
      yield and sustainable agriculture.

PMID- 29024389
TI  - In vivo properties of the disaggregase function of J-proteins and Hsc70 in
      Caenorhabditis elegans stress and aging.
AB  - Protein aggregation is enhanced upon exposure to various stress conditions and
      aging, which suggests that the quality control machinery regulating protein
      homeostasis could exhibit varied capacities in different stages of organismal
      lifespan. Recently, an efficient metazoan disaggregase activity was identified in
      vitro, which requires the Hsp70 chaperone and Hsp110 nucleotide exchange factor,
      together with single or cooperating J-protein co-chaperones of classes A and B.
      Here, we describe how the orthologous Hsp70s and J-protein of Caenorhabditis
      elegans work together to resolve protein aggregates both in vivo and in vitro to
      benefit organismal health. Using an RNAi knockdown approach, we show that class A
      and B J-proteins cooperate to form an interactive flexible network that
      relocalizes to protein aggregates upon heat shock and preferentially recruits
      constitutive Hsc70 to disaggregate heat-induced protein aggregates and polyQ
      aggregates that form in an age-dependent manner. Cooperation between class A and
      B J-proteins is also required for organismal health and promotes thermotolerance,
      maintenance of fecundity, and extended viability after heat stress. This
      disaggregase function of J-proteins and Hsc70 therefore constitutes a powerful
      regulatory network that is key to Hsc70-based protein quality control mechanisms
      in metazoa with a central role in the clearance of aggregates, stress recovery,
      and organismal fitness in aging.

PMID- 29024392
TI  - Is the kidney donor profile index (KDPI) universal or UNOS-specific?

PMID- 29024393
TI  - Directed Assembly of Gold Nanorods by Terminal-Base Pairing of Surface-Grafted
      DNA.
AB  - Directed assemblies of anisotropic metal nanoparticles exhibit attractive
      physical and chemical properties. However, an effective methodology to prepare
      differently directed assemblies from the same anisotropic nanoparticles is not
      yet available. Gold nanorods (AuNRs) region-selectively modified with different
      DNA strands can form side-by-side (SBS) and end-to-end (ETE) assemblies in a non
      crosslinking manner. When the complementary DNA is hybridized to the surface
      bound DNA, stacking interaction between the blunt ends takes place in the
      designated regions. Such AuNRs assemble into highly ordered structures, assisted
      by capillary forces emerging on the substrate surface. Moreover, insertion of a
      mercury(II)-mediated thymine-thymine base pair into the periphery of the DNA
      layer allows selective formation of the SBS or ETE assemblies from the strictly
      identical AuNRs with or without mercury(II).

PMID- 29024391
TI  - Orthogonal Expression of an Artificial Metalloenzyme for Abiotic Catalysis.
AB  - A cytochrome P450 was engineered to selectively incorporate Ir(Me)
      deuteroporphyrin IX (Ir(Me)-DPIX), in lieu of heme, in bacterial cells. Cofactor
      selectivity was altered by introducing mutations within the heme-binding pocket
      to discriminate the deuteroporphyrin macrocycle, in combination with mutations to
      the P450 axial cysteine to accommodate a pendant methyl group on the Ir(Me)
      center. This artificial metalloenzyme was investigated for activity in non-native
      metallocarbenoid-mediated olefin cyclopropanation reactions and showed enhanced
      activity for aliphatic and electron-deficient olefins when compared to the native
      heme enzyme. This work provides a general strategy to augment the chemical
      functionality of heme enzymes in cells with application towards abiotic
      catalysis.

PMID- 29024394
TI  - Encapsulating Co2 P@C Core-Shell Nanoparticles in a Porous Carbon Sandwich as
      Dual-Doped Electrocatalyst for Hydrogen Evolution.
AB  - A highly efficient and pH-universal hydrogen evolution reaction (HER)
      electrocatalyst with a sandwich-architecture constructed using zero-dimensional N
      and P-dual-doped core-shell Co2 P@C nanoparticles embedded into a 3 D porous
      carbon sandwich (Co2 P@N,P-C/CG) was synthesized through a facile two-step
      hydrothermal carbonization and pyrolysis method. The interfacial electron
      transfer rate and the number of active sites increased owing to the synergistic
      effect between the N,P-dual-doped Co2 P@C core-shell and sandwich-nanostructured
      substrates. The presence of a high surface area and large pore sizes improved the
      mass-transfer dynamics. This nanohybrid showed remarkable electrocatalytic
      activity toward the HER in a wide pH range with good stability. The computational
      study and experiments revealed that the carbon atoms close to the N and P dopants
      on the shell of Co2 P@N,P-C were effective active sites for HER catalysis and
      that both Co2 P and the N,P dopants gave rise to an optimized binding free energy
      of H on the active sites.

PMID- 29024395
TI  - Deep eutectic solvent based magnetic nanofluid in the development of stir bar
      sorptive dispersive microextraction: An efficient hyphenated sample preparation
      for ultra-trace nitroaromatic explosives extraction in wastewater.
AB  - A deep eutectic solvent based magnetic nanofluid was coupled with stir bar
      sorptive dispersive microextraction as a hyphenated sample preparation technique.
      The neodymium core magnetic stir bar was coated physically with nanofluid of
      magnetic carbon nanotube nanocomposites and deep eutectic solvents. The prepared
      nanofluid has magnetic and strong sorbing properties and is compatible with gas
      chromatography. In this nanofluid, the deep eutectic solvent acts simultaneously
      as both carrier and stabilizer for magnetic nanotubes. The predominant
      experimental variables affecting the extraction efficiency of nitroaromatic
      compounds were evaluated. Under the optimized conditions, the limit of detection
      and enrichment factor were in the range of 0.2-4.9 ng/L and 852-1480,
      respectively. The relative standard deviations were between 5.6 and 10.2% (n =
      6). Method validation was performed by both spiking-recovery method and
      comparison of results with other methods. Finally, the proposed method was
      successfully applied for the extraction and pre-concentration of nitroaromatic
      explosives in water samples, followed by determination by gas chromatography with
      micro-electron capture detection.

PMID- 29024396
TI  - Health Impact of Climate Change in Older People: An Integrative Review and
      Implications for Nursing.
AB  - PURPOSE: Older people account for the highest proportion of mortality from
      extreme weather events associated with climate change. This article aims to
      describe the health impacts of climate change on older people. TYPE OF STUDY: An
      integrative review was conducted with 30 studies retrieved from PubMed, EBSCO,
      and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) on
      climate stressors, determinants of resilient capacity, risk factors, and health
      outcomes. FINDINGS: Heat, temperature variability, and air pollution increase
      mortality risk in older people, especially from cardiovascular and respiratory
      diseases. Floods are linked with increasing incidence of post-traumatic stress
      disorder, depression, and anxiety. Facing these adversities, older people exhibit
      both vulnerability and resilience. CONCLUSIONS: Research gaps exist in
      understanding the full spectrum of the resilience experience of older people, and
      appreciating areas wherein nursing can play a pivotal role. CLINICAL RELEVANCE:
      Recognizing the vulnerabilities of older people in the context of climate change
      is important. Identifying opportunities to promote resilience is an important
      focus for nurses to develop tailored and targeted nursing interventions.

PMID- 29024397
TI  - Li4 Ti5 O12 Anode: Structural Design from Material to Electrode and the
      Construction of Energy Storage Devices.
AB  - Spinel Li4 Ti5 O12 , known as a zero-strain material, is capable to be a
      competent anode material for promising applications in state-of-art
      electrochemical energy storage devices (EESDs). Compared with commercial
      graphite, spinel Li4 Ti5 O12 offers a high operating potential of ~1.55 V vs
      Li/Li+ , negligible volume expansion during Li+ intercalation process and
      excellent thermal stability, leading to high safety and favorable cyclability.
      Despite the merits of Li4 Ti5 O12 been presented, there still remains the issue
      of Li4 Ti5 O12 suffering from poor electronic conductivity, manifesting
      disadvantageous rate performance. Typically, a material modification process of
      Li4 Ti5 O12 will be proposed to overcome such an issue. However, the previous
      reports have made few investigations and achievements to analyze the subsequent
      processes after a material modification process. In this review, we attempt to
      put considerable interest in complete device design and assembly process with its
      material structure design (or modification process), electrode structure design
      and device construction design. Moreover, we have systematically concluded a
      series of representative design schemes, which can be divided into three major
      categories involving: (1) nanostructures design, conductive material coating
      process and doping process on material level; (2) self-supporting or flexible
      electrode structure design on electrode level; (3) rational assembling of lithium
      ion full cell or lithium ion capacitor on device level. We believe that these
      rational designs can give an advanced performance for Li4 Ti5 O12 -based energy
      storage device and deliver a deep inspiration.

PMID- 29024398
TI  - High-Throughput Feasible Screening Tool for Determining Enzyme Stabilities
      against Organic Solvents Directly from Crude Extracts.
AB  - Biotransformations in organic chemistry frequently suffer from limitations caused
      by low water-solubility of substrates and product inhibition. Both, usually are
      addressed by the addition of organic cosolvents, which often accompanies at the
      expense of enzyme stability. A common method for measuring enzyme stability is to
      determine the melting temperature (Tm ) of the enzyme. However, current methods
      are limited to the application of purified enzymes. Herein, for the first time,
      an easy and fast (<1 h) high-throughput feasible method to determine enzyme
      stabilities directly from crude extracts is reported. In pure buffer, the Tm
      value measured in the crude extract was identical to that obtained for the
      purified enzyme. Through the addition of different organic compounds, the Tm
      values in the crude extract differed by up to 2.4  degrees C from that of the
      purified enzymes due to the presence of the host-cell proteins. Thus, the
      measurement of enzyme stabilities in crude extracts appears to represent
      conditions in whole-cell catalysts even better. The applied nano differential
      scanning fluorimetry technology is further proven to be suitable for whole-cell
      catalysts with two overexpressed enzymes; thus representing a tool for the rapid
      screening of natural and mutant enzyme libraries in terms of process stability
      for challenging biotransformations.

PMID- 29024399
TI  - High magnesium prevents matrix vesicle-mediated mineralization in human bone
      marrow-derived mesenchymal stem cells via mitochondrial pathway and autophagy.
AB  - Magnesium, as a physiological calcium antagonist, plays a vital role in the bone
      metabolism and the balance between magnesium and calcium is crucial in bone
      physiology. We recently demonstrated that matrix mineralization in human bone
      marrow-derived mesenchymal stem cells (hBMSCs) can be suppressed by high Mg2+ .
      However, a complete understanding of the mechanisms involved still remains to be
      elucidated. As mitochondrial calcium phosphate granules depletion manifests
      concurrently with the appearance of matrix vesicles (MVs) and autophagy are
      associated with matrix mineralization, we studied the effect of high
      extracellular Mg2+ on these pathways. Our results first demonstrated that high
      Mg2+ has a significant inhibitory effect on the generalization of extracellular
      mineral aggregates and the expression of collagen 1 along which the mineral
      crystals grow. Transmission electron microscope results showed that less amount
      of MVs were observed inside hBMSCs treated with high Mg2+ and high Mg2+ inhibited
      the release of MVs. In addition, high Mg2+ significantly suppressed mitochondrial
      Ca2+ accumulation. Autophagy is promoted as a response to osteogenesis of hBMSCs.
      High Mg2+ inhibited the level of autophagy upon osteogenesis and autophagy
      inhibitor 3-MA significantly suppressed mineralization. Exogenous ATP can reverse
      the inhibitory effect of high Mg2+ by increasing the level of autophagy. Taken
      together, our results indicate that high Mg2+ may modulate MVs-mediated
      mineralization via suppressing mitochondrial Ca2+ intensity and regulates
      autophagy of hBMSCs upon osteogenesis, resulting in decreased extracellular
      mineralized matrix deposition. Our results contribute to the understanding of the
      role of magnesium homeostasis in osteoporosis and the design of magnesium alloys.

PMID- 29024400
TI  - Biocatalytic Routes to Enantiomerically Enriched Dibenz[c,e]azepines.
AB  - Biocatalytic retrosynthetic analysis of dibenz[c,e]azepines has highlighted the
      use of imine reductase (IRED) and omega-transaminase (omega-TA) biocatalysts to
      establish the key stereocentres of these molecules. Several enantiocomplementary
      IREDs were identified for the synthesis of (R)- and (S)-5-methyl-6,7-dihydro-5H
      dibenz[c,e]azepine with excellent enantioselectivity, by reduction of the parent
      imines. Crystallographic evidence suggests that IREDs may be able to bind one
      conformer of the imine substrate such that, upon reduction, the major product
      conformer is generated directly. omega-TA biocatalysts were also successfully
      employed for the production of enantiopure 1-(2-bromophenyl)ethan-1-amine, thus
      enabling an orthogonal route for the installation of chirality into
      dibenz[c,e]azepine framework.

PMID- 29024401
TI  - Constituents of the Argentine Liverwort Plagiochila diversifolia and Their
      Insecticidal Activities.
AB  - Three new compounds, a bicyclogermacrene (1) and two 2,3-secoaromadendrane esters
      (2 and 3), together with (13S)-13-hydroxylabda-8,14-diene (4), fusicogigantone B
      (5), 3alpha,14-diacetoxy-2-hydoxybicyclogermacrene (6), fusicogigantone A (7),
      neofuranoplagiochilal (8), plagiochiline B (9), furanoplagiochilal (10), trans
      nerolidol, spathulenol, alpha-tocopherol, and (+)-globulol were isolated from an
      Argentine collection of Plagiochila diversifolia. Their structures were
      elucidated by extensive mono and bidimensional NMR studies. Compounds 4, 5, and
      6, incorporated to the larval diet at 100 MUg per g of diet, reduced the larval
      growth of Spodoptera frugiperda (Lepidoptera: Noctuidae) by 70 +/- 25, 57 +/- 23,
      and 33 +/- 16%, respectively. Compounds 4 and 5 produced 70% and 60% larval
      mortality at early instars. The latter also showed antifeedant properties in the
      Choice Test, with a feeding ratio of 0.54 +/- 0.16.

PMID- 29024402
TI  - Blueberry Metabolites Attenuate Lipotoxicity-Induced Endothelial Dysfunction.
AB  - SCOPE: Lipotoxicity-induced endothelial dysfunction is an important vascular
      complication associated with diabetes. Clinical studies support the vascular
      benefits of blueberry anthocyanins, but the underlying mechanism is unclear. The
      hypothesis that metabolites of blueberry anthocyanins attenuate lipotoxicity
      induced endothelial dysfunction was tested. METHODS AND RESULTS: Human aortic
      endothelial cells (HAECs) were treated for 6 h with either: (i) the parent
      anthocyanins (malvidin-3-glucoside and cyanidin-3-glucoside); or (ii) the
      blueberry metabolites (hydroxyhippuric acid, hippuric acid, benzoic acid-4
      sulfate, isovanillic acid-3-sulfate, and vanillic acid-4-sulfate), at
      concentrations known to circulate in humans following blueberry consumption. For
      the last 5 h HAECs were treated with palmitate or vehicle. HAECs treated with
      palmitate displayed elevated reactive oxygen species generation, increased mRNA
      expression of NOX4, chemokines, adhesion molecules, and IkappaBalpha, exaggerated
      monocyte binding, and suppressed nitric oxide production. Of note, the damaging
      effects of palmitate were ameliorated in HAECs treated with blueberry metabolites
      but not parent anthocyanins. Further, important translational relevance of these
      results was provided by our observation that palmitate-induced endothelial
      dysfunction was lessened in arterial segments that incubated concurrently with
      blueberry metabolites. CONCLUSION: The presented findings indicate that the
      vascular benefits of blueberry anthocyanins are mediated by their metabolites.
      Blueberries might complement existing therapies to lessen vascular complications.

PMID- 29024403
TI  - Polymicrobial Bacteremia Involving Comamonas testosteroni in a Patient on
      Dialysis With Acute Appendicitis.

PMID- 29024404
TI  - Removal of Sacral Nerve Stimulation Devices for Magnetic Resonance Imaging: What
      Happens Next?
AB  - INTRODUCTION: Sacral neuromodulation (SNM) devices (Medtronic, Minneapolis, MN,
      USA) are not approved to undergo magnetic resonance imaging (MRI) of sites other
      than the head. When MRIs are required, devices are often removed prior to
      imaging. We reviewed the prevalence of device removal for MRI at a large academic
      institution and the subsequent clinical course of these patients. METHODS: A
      retrospective review of all SNM explants from 2009-2015 was performed. Cases
      explanted for MRI were analyzed to collect demographics, clinical
      characteristics, and postremoval management. Descriptive statistics were
      calculated. RESULTS: Ninety patients underwent SNM device removal, with 21 (23%)
      occurring for MRI. At explant, 20 patients (95%) were female and median age was
      66 years. Suboptimal symptom control from SNM was noted in seven (33%) of these
      patients preoperatively. Of those explanted, six (29%) required MRI for
      neurologic and 10 (48%) for orthopedic concerns. The remaining MRI indications
      included abdominal masses (10%), genitourinary disease (5%), surveillance for
      prior malignancy (5%), and cardiac disease (5%). Only 16 (76%) patients explanted
      ultimately underwent MRI. MRI results impacted clinical management in 9/16 (56%)
      of the imaged patients. Only two (10%) of explanted patients underwent device
      replacement. CONCLUSIONS: In patients receiving SNM therapy, device removal for
      MRI is most commonly due to orthopedic and neurologic pathologies. About half of
      the MRIs performed impacted non-GU clinical management. It is of paramount
      importance to confirm the necessity of MRI before removing a functional SNM
      device. Since SNM replacement was rare in this cohort, research is needed on the
      safety of various MRI types with SNM devices in vivo.

PMID- 29024405
TI  - Current status of liver transplantation for cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is the second most common liver cancer, and it is
      associated with a poor prognosis. CCA can be divided into intrahepatic, hilar,
      and distal. Despite the subtype, the median survival is 12-24 months without
      treatment. Liver transplantation (LT) is recognized worldwide as a curative
      option for hepatocellular carcinoma. On the other hand, the initial results for
      LT for CCA were very poor mainly due to a lack of adequate patient selection. In
      the last 2 decades, improvements have been made in the management of unresectable
      hilar CCA, and the results of LT after neoadjuvant chemoradiation have been shown
      to be promising. This has prompted a consideration of hilar CCA as an indication
      for LT in some centers. Furthermore, some recent research has shown promising
      results after LT for patients with early stages of intrahepatic CCA. A better
      understanding of the best tools to prognosticate the outcomes of LT for CCA is
      still needed. Here, we aimed to review the role of LT for the treatment of
      patients with perihilar and intrahepatic CCA. Also, we will discuss the most
      recent advances in the field and the future direction of the management of this
      disease in an era of transplantation oncology. Liver Transplantation 24 294-303
      2018 AASLD.

PMID- 29024406
TI  - Sodium Iodide (NaI)-Catalyzed Cross-Coupling for C-S Bond Formation via Oxidative
      Dehydrogenation: Cheap, Direct Access to Unsymmetrical Aryl Sulfides.
AB  - A simple and practical NaI-catalyzed direct C-H sulfenylation of arenes has been
      developed under air. In this reaction, aryl sulfides were obtained in moderate to
      excellent yields with high regioselectivity from readily available aromatic
      compounds and aryl/alkyl thiols, even on gram scale. To demonstrate the
      practicability of this reaction, two bioactive compound skeletons were
      synthesized in good yields. This method can also be used to late-stage
      modification of curcumin.

PMID- 29024407
TI  - Ghrelin deletion protects against age-associated hepatic steatosis by
      downregulating the C/EBPalpha-p300/DGAT1 pathway.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease
      worldwide. NAFLD usually begins as low-grade hepatic steatosis which further
      progresses in an age-dependent manner to nonalcoholic steatohepatitis (NASH),
      fibrosis, cirrhosis, and hepatocellular carcinoma in some patients. Ghrelin is a
      hormone known to promote adiposity in rodents and humans, but its potential role
      in hepatic steatosis is unknown. We hypothesized that genetic ghrelin deletion
      will protect against the development of age-related hepatic steatosis. To examine
      this hypothesis, we utilized ghrelin knockout (KO) mice. Although no different in
      young animals (3 months old), we found that at 20 months of age, ghrelin KO mice
      have significantly reduced hepatic steatosis compared to aged-matched wild-type
      (WT) mice. Examination of molecular pathways by which deletion of ghrelin reduces
      steatosis showed that the increase in expression of diacylglycerol O
      acyltransferase-1 (DGAT1), one of the key enzymes of triglyceride (TG) synthesis,
      seen with age in WT mice, is not present in KO mice. This was due to the lack of
      activation of CCAAT/enhancer binding protein-alpha (C/EBPalpha) protein and
      subsequent reduction of C/EBPalpha-p300 complexes. These complexes were abundant
      in livers of old WT mice and were bound to and activated the DGAT1 promoter.
      However, the C/EBPalpha-p300 complexes were not detected on the DGAT1 promoter in
      livers of old KO mice resulting in lower levels of the enzyme. In conclusion,
      these studies demonstrate the mechanism by which ghrelin deletion prevents age
      associated hepatic steatosis and suggest that targeting this pathway may offer
      therapeutic benefit for NAFLD.

PMID- 29024408
TI  - Effects of glucagon-like peptide-1 receptor agonists on cardiovascular risk
      factors: A narrative review of head-to-head comparisons.
AB  - Cardiovascular (CV) disease is the leading cause of death and morbidity in
      patients with type 2 diabetes. Five CV risk factors (blood pressure, resting
      heart rate, body weight, cholesterol levels and blood glucose) are monitored
      routinely as safety and efficacy endpoints in randomized clinical trials for
      diabetes therapies. To determine if different glucagon-like peptide-1 receptor
      agonists (GLP-1RAs) had varying effects on these CV risk factors, we reviewed 16
      head-to-head trials directly comparing GLP-1RAs that included at least one of the
      five factors. Few trials reported statistical differences between GLP-1RAs in
      terms of systolic blood pressure (SBP), body weight and total cholesterol.
      Liraglutide increased heart rate vs its comparators in three separate trials. All
      GLP-1RAs reduced glycated haemoglobin (HbA1c), but exenatide twice daily and
      lixisenatide had statistically smaller effects compared with other GLP-1RAs.
      These descriptive data indicate that individual GLP-1RAs affect CV risk factors
      differently, potentially because of their individual pharmacokinetics and/or
      size. Short-acting GLP-1RAs appeared to result in smaller changes in SBP and
      total cholesterol compared with continuous-acting treatments, while large GLP
      1RAs had a reduced effect on body weight compared with small GLP-1RAs. For
      glycaemic control, short-acting GLP-1RAs had a greater impact on postprandial
      glucose levels vs continuous-acting GLP-1RAs, but for fasting plasma glucose
      levels and HbA1c, continuous-acting treatments had the greater effect. No
      differentiating trends were obvious in heart rate data. These diverse actions of
      GLP-1RAs on CV risk factors should aid individualized patient treatment.

PMID- 29024410
TI  - Eight weeks of omeprazole 20 mg significantly reduces both laryngopharyngeal
      reflux and comorbid chronic rhinosinusitis signs and symptoms: Randomised, double
      blind, placebo-controlled trial.
AB  - OBJECTIVES: Gastroesophageal reflux recommended treatment (dose and duration)
      with proton-pump inhibitor (PPI) compared to placebo significantly reduces the
      signs and symptoms of laryngopharyngeal reflux (LPR) and comorbid chronic
      rhinosinusitis (CRS). DESIGN: Double-blind randomised placebo-controlled trial.
      SETTING: Eight weeks of treatment with omeprazole 20 mg once daily (OD).
      PARTICIPANTS: Sixty patients (28 women, aged 19-87 years) with diagnosed LPR and
      comorbid CRS. MAIN OUTCOME MEASURES: Significant reduction in signs and symptoms
      (reflux symptom index (RSI) score as subjective, and reflux finding score (RFS)
      as objective measure) of LPR after 8 weeks of treatment with omeprazole 20 mg OD
      when compared to placebo. Secondary objectives were significant reduction in
      signs and symptoms of comorbid CRS after 8 weeks of treatment with omeprazole 20
      mg OD when compared to placebo and the association of the severity of signs and
      symptoms of LPR with the ones of CRS. RESULTS: RSI and RFS decreased
      significantly more in the active treatment group after 8 weeks compared to
      placebo (P < .001 for both). CRS and endoscopy scoring decreased both
      significantly more in the active group after 8 weeks compared to placebo (P <
      .001 for both). CRS scoring significantly correlated with RSI (R = 0.312, P =
      .015) but not with RFS (R = 0.199, P = .127). CONCLUSIONS: The results of our
      trial suggest that omeprazole 20 mg OD for 8 weeks was effective in reducing
      signs and symptoms of both LPR and CRS, although in most patients still present
      at the end of the trial.

PMID- 29024409
TI  - The natural agent rhein induces beta-catenin degradation and tumour growth
      arrest.
AB  - The natural agent rhein is an ananthraquinone derivative of rhubarb, which has
      anticancer effects. To determine the mechanisms underlying the anticancer effects
      of rhein, we detected the effect of rhein on several oncoproteins. Here, we show
      that rhein induces beta-catenin degradation in both hepatoma cell HepG2 and
      cervical cancer cell Hela. Treatment of HepG2 and Hela cells with rhein shortens
      the half-life of beta-catenin. The proteasome inhibitor MG132 blunts the
      downregulation of beta-catenin by rhein. The induction of beta-catenin
      degradation by rhein is dependent on GSK3 but independent of Akt. Treatment of
      HepG2 and Hela cells with GSK3 inhibitor or GSK3beta knockdown abrogates the
      effect of rhein on beta-catenin. GSK3beta knockdown compromises the inhibition of
      HepG2 and Hela cell growth by rhein. Furthermore, rhein dose not downregulate
      beta-catenin mutant that is deficient of phosphorylation at multiple residues
      including Ser33, Ser37, Thr41 and Ser45. Moreover, rhein induces cell cycle
      arrest at S phase in both HepG2 and Hela cells. Intraperitoneal administration of
      rhein suppresses tumour cells proliferation and tumour growth in HepG2 xenografts
      model. Finally, the levels of beta-catenin are reduced in rhein-treated tumours.
      These data demonstrate that rhein can induce beta-catenin degradation and inhibit
      tumour growth.

PMID- 29024411
TI  - Double Catalytic Kinetic Resolution (DoCKR) of Acyclic anti-1,3-Diols: The
      Additive Horeau Amplification.
AB  - The concept of a synergistic double catalytic kinetic resolution (DoCKR) as
      described in this article was successfully applied to racemic acyclic anti-1,3
      diols, a common motif in natural products. This process takes advantage of an
      additive Horeau amplification involving two successive enantioselective
      organocatalytic acylation reactions, and leads to diesters and recovered diols
      with high enantiopurities. It was first developed with C2 -symmetrical diols and
      then further extended to non-C2 -symmetrical anti diols to prepare useful chiral
      building blocks. The protocol is highly practical as it only requires 1 mol % of
      a commercially available organocatalyst and leads to easily separable products.
      This procedure was applied to the shortest reported total synthesis of (+)
      cryptocaryalactone, a natural product with anti-germinative activity.

PMID- 29024412
TI  - Risk of posttransplant hepatocellular carcinoma recurrence is greater in
      recipients with higher platelet counts in living donor liver transplantation.
AB  - Platelets interact with tumor cells and promote metastasis. The importance of
      platelets in posttransplant hepatocellular carcinoma (HCC) recurrence is unclear.
      Thus, we aimed to evaluate the association between preoperative platelet count
      (PLT) and HCC recurrence after living donor liver transplantation. Of 359
      recipients of livers from living donors for HCC, 209 of 240 patients who had
      preoperative PLT <=75 * 109 /L were matched with 97 of 119 patients who had
      preoperative PLT >75 * 109 /L using propensity score matching, with an unfixed
      matching ratio based on factors such as tumor biology. The cutoff value of 75 *
      109 /L was set based on optimum stratification analysis. Survival analysis was
      performed with death as a competing risk event. The primary outcome was overall
      HCC recurrence. The median follow-up time was 59 months. Before matching,
      recurrence probability at 1, 2, and 5 years after transplantation was 4.7%, 9.2%,
      and 11.3% for the low platelet group and 14.5%, 23.0%, and 30.5% for the high
      platelet group. Recurrence risk was significantly greater in the high platelet
      group in both univariate (hazard ratio [HR] = 3.09; 95% confidence interval [CI],
      1.86-5.14; P < 0.001) and multivariate analyses (HR = 2.10; 95% CI, 1.23-3.60; P
      =  0.007). In the matched analysis, recurrence risk was also greater in the high
      platelet group in both univariate (HR = 2.33; 95% CI, 1.36-4.01; P =  0.002) and
      multivariate analyses (HR = 1.90; 95% CI, 1.02-3.54; P =  0.04). Preoperative PLT
      had no interaction with the Milan criteria, alpha-fetoprotein level, Edmonson
      grade, microvascular invasion, or intrahepatic metastasis. Incorporation of
      preoperative PLT into the Milan criteria significantly improved predictive power.
      Inflammation-based scores including neutrophil-to-lymphocyte ratio, platelet-to
      lymphocyte ratio, and the inflammation-based index did not show superiority to
      preoperative PLT in predicting HCC recurrence. In conclusion, preoperative PLT
      appears to be an important host factor affecting HCC recurrence after living
      donor liver transplantation. Liver Transplantation 24 44-55 2018 AASLD.

PMID- 29024413
TI  - Deep tissue loads in the seated buttocks on an off-loading wheelchair cushion
      versus air-cell-based and foam cushions: finite element studies.
AB  - For wheelchair users, a common injury is a sitting-acquired pressure ulcer (PU)
      which typically onsets near the interface between the ischial tuberosity (IT) and
      the overlying soft tissues. The risk of developing PUs can be reduced
      considerably if an adequate cushion is placed on the wheelchair in order to
      protect tissues from PUs by minimising interface mechanical loads between the
      body and cushion and also, exposure to internal soft tissue loads. In this work,
      we studied the biomechanical performances of an off-loading (OL) cushion with
      limited adjustability, in comparison to a standard foam cushion and a fully
      adjustable air-cell-based (ACB) cushion. These different cushion design
      approaches were methodologically and quantitatively analysed and compared here
      using a finite element (FE) modelling framework. We determined the internal
      mechanical deformations, strains and stresses in soft tissues of the seated
      buttocks during symmetric sitting, in a specific anatomy of a person with a
      spinal cord injury that was acquired during sitting in an open, magnetic
      resonance imaging configuration. Our results have shown that strains and stresses
      in muscle, fat and skin tissues are orders of magnitude lower for the ACB cushion
      with respect to the standard foam and OL cushions. The OL cushion design has
      taken the approach of protecting at-risk sites of the buttocks by transferring
      local internal tissue loads away from the ITs and towards the greater
      trochanters, at the price of increasing exposure to internal tissue loads at
      sites other than the ITs. The ACB cushion design, however, has taken a different
      approach, that is, immersion and envelopment of the entire buttocks structure,
      which is useful for minimising the exposure to internal tissue loads throughout
      the whole buttocks. Quantifying performances of wheelchair cushions using FE
      modelling provides insights into deep tissue loads, which is essential for
      informed decision-making in developing sitting solutions for individuals at risk,
      as well as for patient groups.

PMID- 29024414
TI  - Nucleosomes Exhibit Non-uniform Unwrapping Along Native Chromatin Fibers with
      Increasing Salt Concentration as Revealed by Direct Imaging in a Microfluidic
      Channel.
AB  - Identifying the distribution of the higher-order structure of chromatin - a
      complex of DNA and proteins - along genomic DNA can clarify the mechanisms
      underlying cell development and differentiation, including gene regulation.
      However, genome-wide analysis of this distribution at the single-cell level
      remains an outstanding challenge. Here, the authors report a new method for
      investigating changes in and the distribution of higher-order structures along
      native chromatin fibers - ranging over 100 um in length - relative to changes in
      salt concentration. To this end, the authors developed a microfluidic platform
      that enabled us to isolate chromatin fibers from single cells and tether them to
      microstructures in a microfluidic channel without fragmentation. The fibers were
      then exposed to varying concentrations of salt solution under microscopic
      observation. As a result, the fibers are non-uniformly elongated by up to 2-3
      times along the fiber axis as salt concentration was increased from 0 to 3 M,
      suggesting that chromosome structural stability is non-uniformly distributed
      along chromatin fibers in their native form. Thus, our system enables direct
      microscopic analysis of individual chromatin fibers from single cells, which can
      provide insights into epigenetic mechanisms of cell development, cell
      differentiation, and carcinogenesis.

PMID- 29024415
TI  - EroS Enzyme from Aliivibrio fischeri Plays Cupid to Choanoflagellates.
AB  - Cupid's bow: A collaborative effort by the King and Clardy laboratories has
      serendipitously identified a bacterial chondroitinase that triggers the
      choanoflagellate S. rosetta to swarm and sexually reproduce. This unprecedented
      interaction between a bacterium and a choanoflagellate could give insights into a
      key evolutionary leap-sexual reproduction.

PMID- 29024416
TI  - Review article: A systematic review of emergency department incident
      classification frameworks.
AB  - As in any part of the hospital system, safety incidents can occur in the ED.
      These incidents arguably have a distinct character, as the ED involves
      unscheduled flows of urgent patients who require disparate services. To aid
      understanding of safety issues and support risk management of the ED, a
      comparison of published ED specific incident classification frameworks was
      performed. A review of emergency medicine, health management and general medical
      publications, using Ovid SP to interrogate Medline (1976-2016) was undertaken to
      identify any type of taxonomy or classification-like framework for ED related
      incidents. These frameworks were then analysed and compared. The review
      identified 17 publications containing an incident classification framework.
      Comparison of factors and themes making up the classification constituent
      elements revealed some commonality, but no overall consistency, nor evolution
      towards an ideal framework. Inconsistency arises from differences in the
      evidential basis and design methodology of classifications, with design itself
      being an inherently subjective process. It was not possible to identify an
      'ideal' incident classification framework for ED risk management, and there is
      significant variation in the selection of categories used by frameworks. The
      variation in classification could risk an unbalanced emphasis in findings through
      application of a particular framework. Design of an ED specific, ideal incident
      classification framework should be informed by a much wider range of theories of
      how organisations and systems work, in addition to clinical and human factors.

PMID- 29024417
TI  - Human CD8+ EMRA T cells display a senescence-associated secretory phenotype
      regulated by p38 MAPK.
AB  - Cellular senescence is accompanied by a senescence-associated secretory phenotype
      (SASP). We show here that primary human senescent CD8+ T cells also display a
      SASP comprising chemokines, cytokines and extracellular matrix remodelling
      proteases that are unique to this subset and contribute to age-associated
      inflammation. We found the CD8+ CD45RA+ CD27- EMRA subset to be the most
      heterogeneous, with a population aligning with the naive T cells and another with
      a closer association to the effector memory subset. However, despite the
      differing processes that give rise to these senescent CD8+ T cells once
      generated, they both adopt a unique secretory profile with no commonality to any
      other subset, aligning more closely with senescence than quiescence. Furthermore,
      we also show that the SASP observed in senescent CD8+ T cells is governed by p38
      MAPK signalling.

PMID- 29024418
TI  - Repair of a critical-size segmental rabbit femur defect using bioglass-beta-TCP
      monoblock, a vascularized periosteal flap and BMP-2.
AB  - Various synthetic bone substitutes are not suitable for reconstructing critical
      size bone defects. This study tested whether a bioglass-beta-tricalcium phosphate
      (beta-TCP) monoblock is effective for repairing critical-size segmental bone
      defects if combined with a vascularized periosteal flap and bone morphogenetic
      protein (BMP)-2. A femoral osteotomy with a gap size of 20 mm was created and
      stabilized using a plate in 40 rabbits.The defect was left untreated (group A) or
      repaired using a monoblock (group B), a monoblock with a vascularized periosteal
      flap (group C), or a monoblock with a vascularized periosteal flap and BMP-2
      (group D). Bone regeneration, vascularization and monoblock degradation were
      analyzed after four and eight weeks using x-ray, hematoxylin-eosin, CD34
      immunohistochemical and Masson's trichrome staining observation and histometric
      evaluation. The radiographic grading score showed a time-dependent increase from
      weeks 4 to 8. At 8-week postoperative, the total new regenerated bone in groups C
      and D was 20.0 +/- 0.3 and 55.5 +/- 8.0 mm2 , respectively, which was
      significantly greater than in group B. Conversely, group D showed less residual
      monoblock than did group C. An increase in microvessel density was also observed
      in groups C and D compared with group B at 4 and 8 weeks postoperative,
      respectively. This study suggests that bioglass-beta-TCP monoblock alone exhibits
      poor potential to repair a 20-mm femoral defect. However, supplementation with a
      vascularized periosteal flap and BMP-2 led to effective vascularization and
      reliable bone regeneration throughout the monoblock, with concordant material
      degradation in a timely manner. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater
      Res Part B: Appl Biomater, 106B: 2148-2156, 2018.

PMID- 29024419
TI  - A multicentre randomised controlled trial evaluating the efficacy of dehydrated
      human amnion/chorion membrane (EpiFix(r) ) allograft for the treatment of venous
      leg ulcers.
AB  - A randomised, controlled, multicentre clinical trial was conducted to evaluate
      the efficacy of dehydrated human amnion/chorion membrane (EpiFix) allograft as an
      adjunct to multilayer compression therapy for the treatment of non-healing full
      thickness venous leg ulcers. We randomly assigned 109 subjects to receive EpiFix
      and multilayer compression (n = 52) or dressings and multilayer compression
      therapy alone (n = 57). Patients were recruited from 15 centres around the USA
      and were followed up for 16 weeks. The primary end point of the study was defined
      as time to complete ulcer healing. Participants receiving weekly application of
      EpiFix and compression were significantly more likely to experience complete
      wound healing than those receiving standard wound care and compression (60%
      versus 35% at 12 weeks, P = 0.0128, and 71% versus 44% at 16 weeks, P = 0.0065).
      A Kaplan-Meier analysis was performed to compare the time-to-healing performance
      with or without EpiFix, showing a significantly improved time to healing using
      the allograft (log-rank P = 0.0110). Cox regression analysis showed that subjects
      treated with EpiFix had a significantly higher probability of complete healing
      within 12 weeks (HR: 2.26, 95% confidence interval 1.25-4.10, P = 0.01) versus
      without EpiFix. These results confirm the advantage of EpiFix allograft as an
      adjunct to multilayer compression therapy for the treatment of non-healing, full
      thickness venous leg ulcers.

PMID- 29024420
TI  - Skin flap vaginal augmentation helps prevent and cure post obstetric fistula
      repair urine leakage: a critical anatomical analysis.
AB  - : Our aim was to describe a new surgical method for prophylaxis/cure of post
      obstetric fistula repair leakage based on restoring vaginal elasticity with
      Singapore skin flap. The rationale for this operation was based on the integral
      theory: scarring removes elasticity required for independent function of
      oppositely acting urethral closure forces so they become 'tethered, forcibly
      opening the urethra when give the signal to close'. Skin graft restores
      elasticity and closure. Used prophylactically with Goh type 4 fistula (n = 45),
      46% were dry against an expected 19%. In patients with successful fistula
      closure, still with severe leakage (n = 24), 71% were dry against an expected
      26%. TWEETABLE ABSTRACT: Singapore skin flap restores elasticity and prevents and
      treats incontinence in patients with successful obstetric fistula repair.

PMID- 29024421
TI  - Generalized estimating equation model to compare drug effects on synovitis of the
      dominant wrist in severe rheumatoid arthritis between tocilizumab versus
      adalimumab versus abatacept using high-resolution ultrasound.
AB  - PURPOSE: The use of biological agents has revolutionized the treatment of
      rheumatoid arthritis (RA). However, details of serial synovial changes in imaging
      evaluation are unclear. Using power Doppler (PD) ultrasound, this study aimed to
      evaluate the comparative efficacy of biologicals for patients with refractory RA,
      with the hope that these findings could aid in clinical decision making. METHODS:
      Patients with RA who received abatacept, adalimumab or tocilizumab therapy were
      enrolled. All underwent gray scale synovial hypertrophy and PD assessments of the
      dominant wrist (dorsal aspect) at baseline and at 1, 3 and 6 months after
      therapy. A generalized estimating equation model was used to compare efficacy
      among the three drugs. RESULTS: Of the 103 patients enrolled, 32 received
      adalimumab, 38 abatacept and 33 tocilizumab. There were no significant
      differences in age or sex among the three groups. All had a treatment response
      according to gray scale (P = 0.000) and PD (P = 0.001) synovitis scores. The
      tocilizumab group had a significantly lower synovial hypertrophy score at 6
      months (P = 0.006), and the adalimumab group also had a lower score although
      without statistical significance (P = 0.043). The adalimumab group had a lower PD
      score than the other two groups (P < 0.05). CONCLUSION: In a 6-month head-to-head
      comparison of patients with RA, tocilizumab and adalimumab had a greater effect
      on reducing synovial hypertrophy, while adalimumab had a greater effect in
      controlling inflammation in PD.

PMID- 29024422
TI  - Vascularization in Ornamented Osteoderms: Physiological Implications in
      Ectothermy and Amphibious Lifestyle in the Crocodylomorphs?
AB  - Vascularization in the core of crocodylian osteoderms, and in their superficial
      pits has been hypothesized to be a key feature involved in physiological
      thermoregulation and/or acidosis buffering during anoxia (apnea). However, up to
      now, there have been no quantitative data showing that the inner, or superficial,
      blood supply of the osteoderms is greater than that occurring in neighboring
      dermal tissues. We provide such data: our results clearly indicate that the
      vascular networks in both the osteoderms and the pits forming their superficial
      ornamentation are denser than in the overlying dermis. These results support
      previous physiological assumptions and indicate that vascularization in
      pseudosuchian (crocodylians and close relatives) ornamented osteoderms could be
      part of a broad eco-physiological adaptation towards ectothermy and aquatic
      ambush predation acquired by the crocodylomorphs during their post-Triassic
      evolution. Moreover, regressions demonstrate that the number of enclosed vessels
      is correlated with the sectional area of the cavities housing them (superficial
      pits and inner cavities). These regressions can be used to infer the degree of
      vascularization on dry and fossilized osteoderms and thus document the evolution
      of the putative function of the osteoderms in the Pseudosuchia. Anat Rec, 2017.
      (c) 2017 Wiley Periodicals, Inc. Anat Rec, 301:175-183, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29024423
TI  - Reply.

PMID- 29024424
TI  - Developing asymmetry in a screening mammogram: A cautionary tale of a missed
      cancer.
AB  - The developing asymmetry has a 12-15% risk of malignancy but poses challenges of
      detection and interpretation due to the lack of typical features of cancer and
      the frequent absence of an ultrasound correlate. Failure to biopsy these lesions
      may lead to delayed diagnosis of breast cancer.

PMID- 29024425
TI  - Multicentre evaluation of magnetic resonance imaging supported transperineal
      prostate biopsy in biopsy-naive men with suspicion of prostate cancer.
AB  - OBJECTIVES: To analyse the detection rates of primary magnetic resonance imaging
      (MRI)-fusion transperineal prostate biopsy using combined targeted and systematic
      core distribution in three tertiary referral centres. PATIENTS AND METHODS: In
      this multicentre, prospective outcome study, 807 consecutive biopsy-naive
      patients underwent MRI-guided transperineal prostate biopsy, as the first
      diagnostic intervention, between 10/2012 and 05/2016. MRI was reported following
      the Prostate Imaging-Reporting and Data System (PI-RADS) criteria. In all, 236
      patients had 18-24 systematic transperineal biopsies only, and 571 patients
      underwent additional targeted biopsies either by MRI-fusion or cognitive
      targeting if PI-RADS >=3 lesions were present. Detection rates for any and
      Gleason score 7-10 cancer in targeted and overall biopsy were calculated and
      predictive values were calculated for different PI-RADS and PSA density (PSAD)
      groups. RESULTS: Cancer was detected in 68% of the patients (546/807) and Gleason
      score 7-10 cancer in 49% (392/807). The negative predictive value of 236 PI-RADS
      1-2 MRI in combination with PSAD of <0.1 ng/mL/mL for Gleason score 7-10 was 0.91
      (95% confidence interval +/- 0.07, 8% of study population). In 418 patients with
      PI-RADS 4-5 lesions using targeted plus systematic biopsies, the cancer detection
      rate of Gleason score 7-10 was significantly higher at 71% vs 59% and 61% with
      either approach alone (P < 0.001). For 153 PI-RADS 3 lesions, the detection rate
      was 31% with no significant difference to systematic biopsies with 27% (P >
      0.05). Limitations include variability of multiparametric MRI (mpMRI) reading and
      Gleason grading. CONCLUSION: MRI-based transperineal biopsy performed at high
      volume tertiary care centres with a significant experience of prostate mpMRI and
      image-guided targeted biopsies yielded high detection rates of Gleason score 7-10
      cancer. Prostate biopsies may not be needed for men with low PSAD and an
      unsuspicious MRI. In patients with high probability lesions, combined targeted
      and systematic biopsies are recommended.

PMID- 29024426
TI  - C-reactive protein gene polymorphisms (rs1205) in Asian Indian patients with
      Takayasu arteritis: Associations and phenotype correlations.
AB  - BACKGROUND/PURPOSE: Normal C-reactive protein (CRP) in active Takayasu arteritis
      (TA) is a dilemma. We attempted to validate our pilot study finding of rs1205 in
      CRP gene being protective against TA. METHODS: Genomic DNA of 104 patients and
      185 sex-matched healthy controls were genotyped for rs1205 by Taqman assay.
      Clinical details, demography, angiographic and activity scores (Indian Takayasu
      arteritis score 2010) were recorded prospectively at baseline and during follow
      up visits for 12 months. Minor allele frequency (MAF) and genotype distribution
      between patients and controls as well as patient subgroups were compared using
      chi2 test with Bonferroni correction (pc ) and logistic regression was performed
      to determine independent associations. RESULTS: The majority of patients (n = 84)
      and controls (n = 166) were females. MAF of T allele of rs1205 was less frequent
      in patients (27%) as compared to controls (37.6%), P = 0.013, pc = 0.026 with an
      odds ratio of 0.632 irrespective of gender. Frequency of CC genotype was higher
      in cases (53.8%) than controls (37.3%), P = 0.006, pc = 0.018. A dominant model
      of genotype-phenotype association revealed CC to be associated with more frequent
      coronary arterial and ascending aorta involvement than the other genotypes
      clubbed together (P = 0.01 and P = 0.014, respectively). Blunted CRP response
      seems to be less frequent in patients with CC genotype (P = 0.064). CONCLUSION: T
      allele of rs1205 in CRP gene was less frequent in TA. CC genotype was associated
      with involvement of coronary arteries and ascending aorta. CC genotype was less
      commonly associated with blunted CRP response (CT + TT > CC).

PMID- 29024427
TI  - Combined liver-kidney perfusion enhances protective effects of normothermic
      perfusion on liver grafts from donation after cardiac death.
AB  - It has been shown that combined liver-kidney normothermic machine perfusion (NMP)
      is able to better maintain the circuit's biochemical milieu. Nevertheless,
      whether the combined perfusion is superior to liver perfusion alone in protecting
      livers from donation after circulatory death (DCD) is unclear. We aimed to test
      the hypothesis and explored the mechanisms. Livers from 15 DCD pig donors were
      subjected to either static cold storage (group A), liver-alone NMP (group B), or
      combined liver-kidney NMP (group C). Livers were preserved for 6 hours and
      reperfused ex vivo for 2 hours to simulate transplantation or were transplanted
      in situ. During perfusion, group C showed an improved acid-base and biochemical
      environment in the circuit over group B. After reperfusion, the architecture of
      the liver grafts was best preserved in group C, followed by group B, then group
      A, as shown by the histology and terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick-end labeling staining of both hepatocytes and
      biliary epithelium. Ki-67 staining showed substantial hepatocyte proliferation
      and biliary epithelial regeneration after perfusion in group B and group C. Group
      C produced more bile in the reperfusion phase than those in group A and group B,
      with more physiological bile composition and less severe biliary epithelium
      injury. Von Willebrand factor-positive endothelial cells and E-selectin
      expression decreased in both group B and group C. Combined liver-kidney NMP not
      only produced more adenosine triphosphate, protected the nitric oxide signaling
      pathway, but also diminished oxidative stress (high mobility group box-1 protein
      and 8-hydroxy-2-deoxy guanosine levels) and inflammatory cytokine (IL6 and IL8)
      release when compared with liver-alone NMP and CS. In addition, the 7-day
      survival rate of liver transplant recipients was higher in group C than that in
      groups A and B. In conclusion, combined liver-kidney NMP can better protect DCD
      livers from warm ischemia and reperfusion injury probably by maintaining the
      stability of the internal environment and by abolishing oxidative stress injury.
      Liver Transplantation 24 67-79 2018 AASLD.

PMID- 29024428
TI  - Heat Shock Protein 60 in Obesity: Effect of Bariatric Surgery and its Relation to
      Inflammation and Cardiovascular Risk.
AB  - OBJECTIVE: Heat shock protein 60 (Hsp60) is an adipokine, and its serum
      concentrations are higher in patients with obesity compared to lean patients.
      This study aimed to analyze the effect of bariatric surgery on circulating
      concentrations of Hsp60 in morbid obesity and their correlation with inflammation
      and metabolic and cardiovascular risk. METHODS: Fifty-three females with morbid
      obesity undergoing bariatric surgery were enrolled. Serum parameters and
      anthropometric measures were obtained at baseline and 3 to 12 months post
      surgery. RESULTS: During the 12-month observation period, Hsp60 decreased
      significantly from 31.6 +/- 4.7 ng/mL at baseline to 22.3 +/- 3.0 ng/mL (3
      months), 26.5 +/- 5.5 (6 months), and 21.1 +/- 3.3 ng/mL (12 months).
      Preoperatively, Hsp60 concentrations correlated positively with total
      cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B (ApoB) and
      negatively with adiponectin. At the end of the observation period, serum Hsp60
      positively correlated with triglycerides, ApoB, HbA1c , and C-reactive protein
      (CRP). Patients in the highest quartile of serum Hsp60 were characterized by
      significantly elevated CRP and interleukin 6 independently of BMI, glycemia, and
      insulinemia. At baseline and 12 months after surgery, Hsp60 positively correlated
      with the ApoB/ApoA1 ratio and the cholesterol/high-density lipoprotein
      cholesterol ratio. CONCLUSIONS: Hsp60 concentrations are elevated in morbid
      obesity and decreased after surgery-induced weight loss. Their correlation with
      inflammatory markers and cardiovascular risk might link obesity and
      cardiovascular disease.

PMID- 29024429
TI  - Genetic barcoding of dark-spored myxomycetes (Amoebozoa)-Identification,
      evaluation and application of a sequence similarity threshold for species
      differentiation in NGS studies.
AB  - Unicellular, eukaryotic organisms (protists) play a key role in soil food webs as
      major predators of microorganisms. However, due to the polyphyletic nature of
      protists, no single universal barcode can be established for this group, and the
      structure of many protistean communities remains unresolved. Plasmodial slime
      moulds (Myxogastria or Myxomycetes) stand out among protists by their formation
      of fruit bodies, which allow for a morphological species concept. By Sanger
      sequencing of a large collection of morphospecies, this study presents the
      largest database to date of dark-spored myxomycetes and evaluate a partial 18S
      SSU gene marker for species annotation. We identify and discuss the use of an
      intraspecific sequence similarity threshold of 99.1% for species differentiation
      (OTU picking) in environmental PCR studies (ePCR) and estimate a hidden diversity
      of putative species, exceeding those of described morphospecies by 99%. When
      applying the identified threshold to an ePCR data set (including sequences from
      both NGS and cloning), we find 64 OTUs of which 21.9% had a direct match (>99.1%
      similarity) to the database and the remaining had on average 90.2 +/- 0.8%
      similarity to their best match, thus thought to represent undiscovered diversity
      of dark-spored myxomycetes.

PMID- 29024430
TI  - Impact of sequence processing and taxonomic classification approaches on
      eukaryotic community structure from environmental samples with emphasis on
      diatoms.
AB  - Next-generation sequencing is a common method for analysing microbial community
      diversity and composition. Configuring an appropriate sequence processing
      strategy within the variety of tools and methods is a nontrivial task and can
      considerably influence the resulting community characteristics. We analysed the
      V4 region of 18S rRNA gene sequences of marine samples by 454-pyrosequencing.
      Along this process, we generated several data sets with QIIME, mothur, and a
      custom-made pipeline based on DNAStar and the phylogenetic tree-based
      PhyloAssigner. For all processing strategies, default parameter settings and
      punctual variations were used. Our results revealed strong differences in total
      number of operational taxonomic units (OTUs), indicating that sequence
      preprocessing and clustering had a major impact on protist diversity estimates.
      However, diversity estimates of the abundant biosphere (abundance of >=1%) were
      reproducible for all conducted processing pipeline versions. A qualitative
      comparison of diatom genera emphasized strong differences between the pipelines
      in which phylogenetic placement of sequences came closest to light microscopy
      based diatom identification. We conclude that diversity studies using different
      sequence processing strategies are comparable if the focus is on higher taxonomic
      levels, and if abundance thresholds are used to filter out OTUs of the rare
      biosphere.

PMID- 29024431
TI  - The Cytoarchitecture of the Telencephalon of Betta Splendens Regan 1910
      (Perciformes: Anabantoidei) with a Stereological Approach to the Supracommissural
      and Postcommissural Nuclei.
AB  - Teleostean fish brains are useful models to study cellular and functional
      specializations along the phylogenesis. The Betta splendens Regan 1910 (Siamese
      fighting fish; Perciformes:Anabantoidei) is known for its aggressive display,
      courtship behavior, nest building, and offspring care. Here, we present novel and
      detailed data about the cytoarchitecture of the olfactory bulb and the
      telencephalic hemispheres of this fish. The hematoxylin-eosin and Nissl
      techniques served to identify brain nuclei (n = 19 males and n = 21 females) and
      for the stereological evaluation of the numerical density of cells and the
      proportion of neurons and glial cells in the ventral telencephalon
      supracommissural (Vs) and postcommissural (Vp) nuclei of adult males and females.
      These nuclei are putative homologs of the sexually dimorphic medial amygdala in
      mammals. The olfactory bulb of Betta splendens consists of 5 concentrically
      arranged layers plus ganglion cells of the terminal nerves. The dorsal
      telencephalon consists of 16 different cell groups. The ventral telencephalon has
      8 nuclei, plus the lateral septal organ and the nuclei of the preoptic area
      forming an anatomical continuum. The rostrocaudal extent of the Vs and Vp is not
      different between sexes. In both nuclei, the proportion of neurons to glial cells
      is approximately 2:1 and the density of neurons and glial cells is not different
      between sexes. These morphological findings can subserve future research on the
      brain function of the Betta splendens and the search for neural sex differences
      in other central areas of this same species, in other teleost species, or yet in
      other related vertebrate group. Anat Rec, 00:000-000, 2017. (c) 2017 Wiley
      Periodicals, Inc. Anat Rec, 301:88-110, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29024432
TI  - Littoral cell angioma of spleen.

PMID- 29024433
TI  - Cation-Induced Stabilization and Denaturation of DNA Origami Nanostructures in
      Urea and Guanidinium Chloride.
AB  - The stability of DNA origami nanostructures under various environmental
      conditions constitutes an important issue in numerous applications, including
      drug delivery, molecular sensing, and single-molecule biophysics. Here, the
      effect of Na+ and Mg2+ concentrations on DNA origami stability is investigated in
      the presence of urea and guanidinium chloride (GdmCl), two strong denaturants
      commonly employed in protein folding studies. While increasing concentrations of
      both cations stabilize the DNA origami nanostructures against urea denaturation,
      they are found to promote DNA origami denaturation by GdmCl. These inverse
      behaviors are rationalized by a salting-out of Gdm+ to the hydrophobic DNA base
      stack. The effect of cation-induced DNA origami denaturation by GdmCl deserves
      consideration in the design of single-molecule studies and may potentially be
      exploited in future applications such as selective denaturation for purification
      purposes.

PMID- 29024434
TI  - WHO guide on the economic evaluation of influenza vaccination.
AB  - Influenza is responsible for substantial morbidity and mortality across the
      globe, with a large share of the total disease burden occurring in low- and
      middle-income countries (LMICs). There have been relatively few economic
      evaluations assessing the value of seasonal influenza vaccination in LMICs. The
      purpose of this guide is to outline the key theoretical concepts and best
      practice in methodologies and to provide guidance on the economic evaluation of
      influenza vaccination in LMICs. It outlines many of the influenza vaccine
      specific challenges and should help to provide a framework for future evaluations
      in the area to build upon.

PMID- 29024436
TI  - Retracted: Effects of Whey Peptides on Cardiovascular Disease Risk Factors.
AB  - Previous studies have shown that peptides derived from milk proteins can improve
      blood pressure. Therefore, the authors tested the blood pressure-lowering effects
      of a hydrolyzed whey protein supplement rich in bioactive peptides. In a 6-week
      controlled study, 30 prehypertensive or stage 1 hypertensive subjects (blood
      pressure >=120/80 mm Hg and <=155/95 mm Hg) were randomized to receive 20 g/d of
      either a hydrolyzed whey protein (active treatment) or an unmodified whey protein
      (control treatment). Blood pressure, blood lipids, safety measures, side effects,
      and diet were evaluated throughout the trial. After completion of treatment, a 4
      week follow-up was conducted. There was a mean reduction of 8.0+3.2 mm Hg in
      systolic blood pressure (P<.05) and of 5.5+/-2.1 mm Hg in diastolic blood
      pressure (P<.05) in the treatment group compared with the control group. Low
      density lipoprotein cholesterol and high-sensitivity C-reactive protein were
      significantly improved by treatment. Whey-derived peptides might be a viable
      treatment option for prehypertensive and/or stage 1 hypertensive populations.

PMID- 29024435
TI  - Efect of longitudinally oriented collagen conduit combined with nerve growth
      factor on nerve regeneration after dog sciatic nerve injury.
AB  - The research on artificial nerve conduits has become a focus of study in
      peripheral nerve reconstruction so as a possible replacement for the treatment of
      autologous nerve grafts in clinics. In this study, we used longitudinally
      oriented collagen conduit (LOCC) combined with nerve growth factor (NGF) to
      reconstruct long distance of sciatic nerve defects (35 mm) in adult dog model.
      The long term follow-up evaluation demonstrated that the LOCC/NGF conduit allowed
      functional and morphological nerve regeneration at the transection site of the
      injured sciatic nerve. Furthermore, the functional study confirmed that when NGF
      was loaded onto LOCC it promoted a better recovery of regenerated axons than LOCC
      alone. The gastrocnemius muscle mass in the LOCC/NGF group was significantly
      greater than in the LOCC alone group. The results indicated that when LOCC
      conduit combined with NGF it would provide a preferential environment for sciatic
      nerve regeneration. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B:
      Appl Biomater, 106B: 2131-2139, 2018.

PMID- 29024438
TI  - American Society of Hypertension, Inc In Memorium: Dr Louis Tobian.

PMID- 29024437
TI  - Prehypertension-What Is It and Should It Be Treated?
AB  - In May 2006, a panel of experts was assembled during the meeting of the American
      Society of Hypertension, Inc to discuss the diagnosis and treatment of
      prehypertension. Is it a real entity? Does it pose a risk? Should it be treated
      entirely with lifestyle interventions or should some patients be placed on
      pharmacologic therapy? The panel was chaired by Dr Marvin Moser, Clinical
      Professor of Medicine at the Yale University School of Medicine, New Haven, CT,
      and Editor in Chief of The Journal of Clinical Hypertension. Panelists included
      Dr Thomas Giles, Professor of Medicine at Louisiana State University, New
      Orleans, LA; Dr Joseph Izzo, Jr, Professor of Medicine at SUNY Buffalo School of
      Medicine, Buffalo, NY; and Dr Henry Black, Roberts Professor of Preventive
      Medicine at the Rush University School of Medicine in Chicago, Chicago, IL.

PMID- 29024439
TI  - Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor.

PMID- 29024440
TI  - Endothelial Vascular Function in Hypertensive Patients After Renin-Angiotensin
      System Blockad.
AB  - It is unclear whether single and combined pharmacologic inhibition of the renin
      angiotensin-aldosterone system have similar effects on endothelial function and
      blood pressure (BP). The authors evaluated 63 hypertensive patients divided into
      4 groups (hydrochlorothiazide 25 mg/d; irbesartan [IRBE] 150 mg/d; quinapril
      [QUIN] 20 mg/d; or IRBE 150 mg/d + QUIN 20 mg/d) and 25 healthy normotensive
      subjects (normal) followed for 12 weeks. Endothelium-dependent dysfunction
      measured as flow-mediated dilation at Weeks 0 and 12 were: normal, 11.5%+/-2.4%
      vs 13.5%+/-2.0%; hydrochlorothiazide, 7.3%+/-2.0% vs 12.8%+/-3.1%; QUIN, 7.2%+/
      2.8% vs 13.2%+/-2.1%; IRBE, 7.1%+/-2.8% vs 13.0%+/-2.9%; and IRBE + QUIN, 7.5%+/
      1.9% vs 12.8%+/-3.0%. Nitroglycerin-mediated responses were: normal, 26.0%+/-1.9%
      vs 24.0%+/-2.5%; hydrochlorothiazide, 17.0%+/-2.2% vs 18.3%+/-2.6%; QUIN, 17.8%+/
      3.2% vs 23.4%+/-3.0%; IRBE, 16.8%+/-3.6% vs 24.7%+/-2.0%; and IRBE + QUIN,
      17.3%+/-3.0% vs 25.1%+/-2.5%. Antihypertensive therapy restored BP to normal and
      improved the endothelium-dependent and -independent dysfunction after renin
      angiotensin-aldosterone system blockade. In a further finding, the combined
      effect of angiotensin-converting enzyme inhibition and angiotensin II type 1
      receptor blockade was not superior to the action of either of these treatments
      separately.

PMID- 29024441
TI  - Therapy: Counseling for Mental Health and Illness.

PMID- 29024442
TI  - Con: Treating hepatitis C virus With direct-acting antivirals: Fear not the
      perceived threat of hepatocellular carcinoma.

PMID- 29024443
TI  - Bioglass enhanced wound healing ability of urine-derived stem cells through
      promoting paracrine effects between stem cells and recipient cells.
AB  - In cell therapy, tissue regeneration ability of stem cells relies on the
      paracrine effects between stem cells and recipient cells. Our recent studies
      demonstrated that, in tissue engineering, bioactive silicates could stimulate
      paracrine effects between stem cells and recipient cells, which enhanced tissue
      generation. Therefore, we proposed that, in cell therapy, it may be an effective
      method to improve tissue regeneration ability of stem cells through activating
      the paracrine effects between stem cells and recipient cells with bioactive
      silicates. As urine-derived stem cells (USCs) have been injected for wound
      healing and bioglass (BG) have shown bioactivity for various types of stem cells,
      in this study, we activated USCs with effective BG ionic products. Then the
      conditioned medium of BG-activated USCs were used to culture endothelial cells
      and fibroblasts as well as co-cultures of endothelial cells and fibroblasts.
      Results showed that growth factor expression in BG-activated USCs was
      upregulated. In addition, paracrine effects between USCs and recipient cells in
      wound healing were stimulated, which resulted in enhanced capillary-like network
      formation of endothelial cells and matrix protein production as well as
      myofibroblast differentiation of fibroblasts. Finally, the BG-activated USCs were
      applied on full-thickness excisional wounds. Results confirmed that BG-activated
      USCs had better wound healing ability through improving angiogenesis and collagen
      deposition in wound sites as compared with USCs without any treatment. Taken
      together, BG can be used to promote wound healing ability of USCs by enhancing
      paracrine effects between USCs and recipient cells.

PMID- 29024444
TI  - Role of esophagogastroduodenoscopy in detecting distal duodenal lesions: A single
      center pilot study in Southern China.
AB  - OBJECTIVE: Esophagogastroduodenoscopy (EGD) is a standard instrument for
      detecting upper gastrointestinal lesions. However, the distal duodenum is often
      missed. This study aimed to clarify the diagnostic role of EGD in the distal
      duodenum. METHODS: This retrospective study enrolled patients with distal
      duodenal lesions who underwent EGD between January 2004 and July 2016 at our
      center. The rate of missed diagnosis using EGD examination was calculated.
      Logistic regression analysis was performed to identify the factors associated
      with the missed diagnoses. RESULTS: Sixty-three patients were included in the
      study. The overall diagnostic rate of distal duodenal lesions on EGD was 58.7%.
      After excluding the patients in whom the EGD did not reach the distal duodenum,
      this rate rose to 82.2%. In univariate analysis, intravenous sedation (26.8% vs
      68.2%, odds ratio [OR] 0.171, P = 0.002), signs of lesions adjacent to the
      stomach (19.4% vs 62.5%, OR 0.099, P = 0.001), prior enteroscopy experience
      (15.0% vs 87.0%, OR 0.026, P < 0.001), and endoscopists with experiences of over
      10 years (13.8% vs 64.7%, OR 0.087, P = 0.000) were associated with a decreased
      risk of missed diagnosis. In multivariate analysis, signs of lesions adjacent to
      the stomach (OR 0.167, P = 0.039) and prior enteroscopy experience (OR 0.035, P <
      0.001) were significant independent protective factors. CONCLUSION: EGD may be
      important in diagnosing distal duodenal lesions. Patients with gastric retention,
      blood in the stomach or erosion in the proximal duodenum may benefit from the
      deep insertion of EGD.

PMID- 29024445
TI  - A rapid bio-optical sensor for diagnosing Q fever in clinical specimens.
AB  - Recent zoonotic outbreaks, such as Zika, Middle East respiratory syndrome and
      Ebola, have highlighted the need for rapid and accurate diagnostic assays that
      can be used to aid pathogen control. Q fever is a zoonotic disease caused by the
      transmission of Coxiella burnetii that can cause serious illness in humans
      through aerosols and is considered a potential bioterrorism agent. However, the
      existing assays are not suitable for the detection of this pathogen due to its
      low levels in real samples. We here describe a rapid bio-optical sensor for the
      accurate detection of Q fever and validate its clinical utility. By combining a
      bio-optical sensor, that transduces the presence of the target DNA based on
      binding-induced changes in the refractive index on the waveguide surface in a
      label-free and real-time manner, with isothermal DNA amplification, this new
      diagnostic tool offers a rapid (<20 min), 1-step DNA amplification/detection
      method. We confirmed the clinical sensitivity (>90%) of the bio-optical sensor by
      detecting C. burnetii in 11 formalin-fixed, paraffin-embedded liver biopsy
      samples from acute Q fever hepatitis patients and in 16 blood plasma samples from
      patients in which Q fever is the cause of fever of unknown origin.

PMID- 29024446
TI  - Baroreflex sensitivity: An algebraic dilemma.

PMID- 29024447
TI  - The influences of a novel anti-adhesion device, thermally cross-linked gelatin
      film on peritoneal dissemination of tumor cells: The in vitro and in vivo
      experiments using murine carcinomatous peritonitis models.
AB  - To create anti-adhesive materials to be more effective and safer, we developed a
      thermally cross-linked gelatin film that showed superior anti-adhesive effects
      with excellent peritoneal regeneration. However, it may act as a convenient
      scaffold for tumor cell growth, thereby accelerating peritoneal dissemination
      when used in surgery for abdominal tumors. In this study, we tried to clarify
      this issue using mouse carcinomatous peritonitis models. First, we examined the
      in vitro tumor cell growth of mouse B16 melanoma or Colon26 cells on the gelatin
      film or the conventional hyarulonate/carboxymethylcellulose film. Tumor cell
      growth on each film was significantly lower than that of the control (no film).
      Next, we conducted the following in vivo experiments: After the parietal
      peritoneum was partially removed and covered with each film or without any film,
      mice were inoculated intraperitoneally with B16 melanoma or Colon26/Nluc cells
      expressing NanoLuc luciferase gene. At 7 days after the operation, we measured
      the weight of B16 melanoma tumors or the NanoLuc activity of Colon26/Nluc cells
      using in vivo imaging at the injured sites. There were no significant differences
      in the weight of the tumors and the NanoLuc activity among the three groups. We
      also observed the survival time of mice receiving the same operation and
      treatments. There was no significant difference in the survival time among the
      three groups. These results suggest that the gelatin film will likely not
      accelerate peritoneal dissemination as a convenient scaffold for tumor cell
      growth when used in surgery for abdominal tumors. (c) 2017 Wiley Periodicals,
      Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2122-2130, 2018.

PMID- 29024449
TI  - Re: Clinical follow up of women after hypertensive disease in pregnancy and
      Moderately elevated blood pressure during pregnancy and odds of hypertension
      later in life: the POUCHmoms longitudinal study Potential mechanisms for pregnant
      and, nonpregnant hypertension.

PMID- 29024448
TI  - Isolated sphenoid sinus opacifications: a systematic review and meta-analysis.
AB  - BACKGROUND: Isolated sphenoid sinus opacifications (ISSOs) represent a relatively
      uncommon disease with the potential for serious complications. To better
      understand this disease, we performed a systematic review to further characterize
      the underlying pathologies, associated symptoms, and treatment outcomes of
      patients with ISSOs. METHODS: A systematic review of ISSO case series was
      performed utilizing the Medline, Embase, Web of Science, and Cochrane databases
      in accordance with guidelines established by PRISMA (Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses). Data of interest included disease
      pathology, associated symptoms, and treatment outcomes. RESULTS: Of the initial
      1051 hits from the 4 databases, 17 articles, with a combined 1133 ISSO patients,
      were ultimately included in the review. On a weighted analysis, the underlying
      pathologies were classified as chronic rhinosinusitis without nasal polyps
      (CRSsNP) (28.3%), mucoceles (20.3%), fungal sinusitis (12.5%), malignant
      neoplasms (7.7%), intracranial lesions (7.0%), benign neoplasms (5.7%), chronic
      rhinosinusitis with nasal polyps (CRSwNP) (3.4%), and other lesions (4.7%).
      Cranial neuropathies were present in 16.3% (95% confidence interval [CI], 10.1
      22.5%) of ISSO patients. A favorable surgical complication rate of 1.5% (95% CI, 
      0.1% to 3.2%) was found in patients undergoing surgery for an ISSO. CONCLUSION:
      ISSOs are caused by diverse pathologies. Given the considerable rates of
      neoplastic disease and cranial neuropathies, patients affected by an ISSO should
      be monitored closely and treated aggressively. Prompt surgical intervention, with
      either diagnostic or therapeutic intent, is often indicated.

PMID- 29024450
TI  - Optical clearing for multiscale biological tissues.
AB  - Three-dimensional reconstruction of tissue structures is essential for biomedical
      research. The development of light microscopes and various fluorescent labeling
      techniques provides powerful tools for this motivation. However, optical imaging
      depth suffers from strong light scattering due to inherent heterogeneity of
      biological tissues. Tissue optical clearing technology provides a distinct
      solution and permits us to image large volumes with high resolution. Until now,
      various clearing methods have been developed. In this study, from the perspective
      of the end users, we review in vitro tissue optical clearing techniques based on
      the sample features in terms of size and age, enumerate the methods suitable for
      immunostaining and lipophilic dyes and summarize the combinations with various
      imaging techniques. We hope this review will be helpful for researchers to choose
      the most suitable clearing method from a variety of protocols to meet their
      specific needs.

PMID- 29024451
TI  - Activation of Group II Metabotropic Glutamate Receptors Increases Proliferation
      but does not Influence Neuronal Differentiation of a Human Neural Stem Cell Line.
AB  - The multiple functions of glutamate include regulation of neural development and
      stem cells. While the importance of the ionotropic glutamate receptors is well
      established, less is known about the role of metabotropic glutamate receptors
      (mGluRs). In this study, we examined the effects of pharmacological activation
      and inhibition of mGluR2/3 on proliferation, differentiation and viability of a
      human neural stem cell line. Immunofluorescence staining revealed the presence of
      mGluR2/3 receptors on both proliferating and differentiating stem cells,
      including cells differentiated into beta-tubulin III-positive immature neurons
      and glial fibrillary acidic protein-positive astrocytes. Stimulation of mGluR2/3
      receptors during cell propagation using the agonist (2S,2'R,3'R)-2-(2',3'
      dicarboxycyclopropyl) glycine (DCG-IV) increased total cell numbers significantly
      (60% compared to untreated controls). This effect could be inhibited by the
      specific antagonist (2S)-2-Amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9
      yl) propanoic acid (LY341495). The antagonist alone had no effect. No significant
      decrease in cell death was found following mGluR2/3 stimulation, suggesting that
      the observed elevation in cell number was not related to cell viability.
      Subsequent differentiation of the cells resulted in a slight decrease in beta
      tubulin III-positive neurons (5.2-3.2% of total cells) for DCG-IV pre-treated
      cultures. Treatment with DCG-IV and LY342495 during cell differentiation alone
      had no such effect. Western blot analysis revealed that the active, dimeric form
      of mGluR2/3 was mainly present on the proliferating cells, which may explain our
      findings. This study emphasizes the importance of glutamate and mGluRs on
      regulation of human neural stem cells and suggests a significant role of mGluR2/3
      during cell proliferation.

PMID- 29024452
TI  - Two-year clinical outcomes of patients treated with overlapping absorb scaffolds:
      An analysis of the ABSORB EXTEND single-arm study.
AB  - BACKGROUND: Preclinical data showed that overlapping (OVP) scaffolds might result
      in delayed healing and strut coverage compared to nonOVP scaffold segments.
      Furthermore, OVP in patients could result in increased periprocedure myocardial
      infarction (MI) rate secondary to side branch occlusion; however, little is known
      whether this may have an impact on long-term clinical outcomes. METHODS: ABSORB
      EXTEND is a prospective, single-arm, open-label clinical study in which 812
      patients were enrolled at 56 sites. In this study, we compared the immediate and
      2-year clinical outcomes of patients with OVP scaffolds (n = 115) to those of
      patients with nonOVP scaffolds (n = 697). The primary objective was the
      comparison of major adverse cardiac event (MACE) (cardiac death, MI and ischemic
      driven target lesion revascularization [TLR]) and scaffold thrombosis (ST) rates
      up to 2 years. RESULTS: Baseline clinical and angiographic characteristics were
      comparable between cohorts except for longer lesions in the OVP patients as
      expected (16.7 +/- 7.3 vs. 11.6 +/- 4.4 mm, P < 0.0001), higher lesion complexity
      (B2) and numerically smaller vessel size. In-hospital, there was a marked
      increase in MACE in the OVP cohort (7.0 vs. 0.9%, P = 0.002), exclusively driven
      by a higher rate of periprocedure MI (7.0 vs. 0.9%, P = 0.002). Long-term MACE
      did not significantly differ between groups (10.4% in the OVP cohort vs. 6.6% in
      the no-OVP group, P = 0.1) with comparable rates of cardiac death (0.9 vs. 1.2%,
      P = 1.0) and ischemia-driven TLR (1.7 vs. 2.5%, P = 1.0). Cumulative incidence of
      MI was higher in the OVP cohort (7.8 vs. 3.0%, P = 0.02). Of note, the rate of MI
      between hospital discharge and 2-year follow-up was lower in the OVP cohort (0.8
      vs. 2.1%, P = 0.04). Cumulative incidence of definite/probable ST was relatively
      low and comparable between groups (1.8 vs. 1.5%, P = 0.7). CONCLUSIONS: In this
      low-to-moderate complex population treated with the ABSORB scaffold the OVP group
      showed a higher incidence of periprocedure MI with no immediate or long-term
      increase in cardiac death, TLR or ST.

PMID- 29024453
TI  - The histopathologic reliability of tissue taken from cadavers within the gross
      anatomy laboratory.
AB  - The purpose of this study was to examine the histopathologic reliability of
      embalmed cadaveric tissue taken from the gross anatomy laboratory. Tissue samples
      from hearts, livers, lungs, and kidneys were collected after the medical
      students' dissection course was completed. All of the cadavers were embalmed in a
      formalin-based fixative solution. The tissue was processed, embedded in paraffin,
      sectioned at six micrometers, and stained with H&E. The microscope slides were
      evaluated by a board certified pathologist to determine whether the cellular
      components of the tissues were preserved at a high enough quality to allow for
      histopathologic diagnosis. There was a statistically significant relationship
      between ratings and organ groups. Across all organs, there was a smaller
      proportion of "poor" ratings. The lung group had the highest percentage of "poor"
      ratings (23.1%). The heart group had the least "poor" ratings (0.0%). The largest
      percentage of "satisfactory" ratings were in the lung group (52.8%), and the
      heart group contained the highest percentage of "good" ratings (58.5%) The lung
      group had the lowest percentage of "good" ratings (24.2%). These results indicate
      that heart tissue is more reliable than lung, kidney, or liver tissue when
      utilizing tissue from the gross anatomy laboratory for research and/or
      educational purposes. This information advises educators and researchers about
      the quality and histopathologic reliability of tissue samples obtained from the
      gross anatomy laboratory. Anat Sci Educ 11: 207-214. (c) 2017 American
      Association of Anatomists.

PMID- 29024455
TI  - The Science of Salt: A regularly updated systematic review of the implementation
      of salt reduction interventions (September 2016-February 2017).
AB  - This periodic review aims to identify, summarize, and appraise studies relating
      to the implementation of salt reduction strategies that were published between
      September 2016 and February 2017. A total of 41 studies were included as relevant
      to the design, assessment, and implementation of salt reduction strategies, and a
      detailed appraisal was conducted on the seven studies that evaluated the impact
      of salt reduction strategies. Of these, three were national studies or included
      large populations and four were conducted in communities with small participant
      sample sizes. Each study used a different strategy for reducing salt intake
      varying from category-specific sodium targets for packaged food to use of a low
      sodium salt substitute to behavior change interventions. Four studies found
      statistically significant decreases in dietary salt intake and one study showed
      statistically significant decreases in mean sodium density of packaged food
      products. Four of the seven studies used either spot or 24-hour urine samples to
      measure dietary salt intake and five were conducted in East or Southeast Asia-two
      of which were in low- and middle-income countries. Study quality varied among the
      seven studies and all except one had one or more risks related to bias.

PMID- 29024456
TI  - Disseminated histoplasmosis in an immuno-competent young male: Role of bone
      marrow examination in rapid diagnosis.
AB  - Fungal infections are usually seen in elderly or immuno-compromised individuals
      particularly with human immunodeficiency virus infection. In immuno-competent
      individuals, they seldom present with overt clinical symptoms. In such cases
      diagnosis is made by combination of tests along with direct microscopic
      visualization of the organism. We present a case of immuno-competent individual
      who presented with unexplained fever and found to have Histoplasma capsulatum
      infection on bone marrow examination.

PMID- 29024454
TI  - Disclosure of Personalized Rheumatoid Arthritis Risk Using Genetics, Biomarkers,
      and Lifestyle Factors to Motivate Health Behavior Improvements: A Randomized
      Controlled Trial.
AB  - OBJECTIVE: To determine the effect of disclosure of rheumatoid arthritis (RA)
      risk personalized with genetics, biomarkers, and lifestyle factors on health
      behavior intentions. METHODS: We performed a randomized controlled trial among
      first-degree relatives without RA. Subjects assigned to the Personalized Risk
      Estimator for Rheumatoid Arthritis (PRE-RA) group received the web-based PRE-RA
      tool for RA risk factor education and disclosure of personalized RA risk
      estimates, including genotype/autoantibody results and behaviors (n = 158).
      Subjects assigned to the comparison arm received standard RA education (n = 80).
      The primary outcome was readiness for change based on the trans-theoretical
      model, using validated contemplation ladder scales. Increased motivation to
      improve RA risk-related behaviors (smoking, diet, exercise, or dental hygiene)
      was defined as an increase in any ladder score compared to baseline, assessed
      immediately, 6 weeks, and 6 months post-intervention. Subjects reported behavior
      change at each visit. We performed intent-to-treat analyses using generalized
      estimating equations for the binary outcome. RESULTS: Subjects randomized to PRE
      RA were more likely to increase ladder scores over post-intervention assessments
      (relative risk 1.23, 95% confidence interval [95% CI] 1.01, 1.51) than those
      randomized to nonpersonalized education. At 6 months, 63.9% of PRE-RA subjects
      and 50.0% of comparison subjects increased motivation to improve behaviors (age
      adjusted difference 15.8%; 95% CI 2.8%, 28.8%). Compared to nonpersonalized
      education, more PRE-RA subjects increased fish intake (45.0% versus 22.1%; P =
      0.005), brushed more frequently (40.7% versus 22.9%; P = 0.01), flossed more
      frequently (55.7% versus 34.8%; P = 0.004), and quit smoking (62.5% versus 0.0%
      among 11 smokers; P = 0.18). CONCLUSION: Disclosure of RA risk personalized with
      genotype/biomarker results and behaviors increased motivation to improve RA risk
      related behaviors. Personalized medicine approaches may motivate health behavior
      improvements for those at risk for RA and provide rationale for larger studies
      evaluating effects of behavior changes on clinical outcomes, such as RA-related
      autoantibody production or RA development.

PMID- 29024457
TI  - Design of Poly-l-Glutamate-Based Complexes for pDNA Delivery.

PMID- 29024458
TI  - From Polymers to Functional Biomaterials.

PMID- 29024459
TI  - Phosphate-Responsive Biomimetic Nanofluidic Diodes Regulated by Polyamine
      Phosphate Interactions: Insights into Their Functional Behavior from Theory and
      Experiment.
AB  - There is currently high interest in developing nanofluidic devices whose
      iontronic output is defined by biological interactions. The fabrication of a
      phosphate responsive nanofluidic diode by using the biological relevant amine
      phosphate interactions is shown. The fabrication procedure includes the
      modification of a track-etched asymmetric (conical) nanochannel with
      polyallylamine (PAH) by electrostatic self-assembly. PAH is the arcaetypical
      model of polyamine and it is further used to address the nanochannels with
      phosphate responsivity. In order to explore the influence that phosphate in
      solution has in the conductance of the modified nanochannels, current-voltage
      measurements using different concentrations of phosphates are performed.
      Furthermore, to have a complete physicochemical understanding of the system,
      experimental data is analyzed using a continuous model based on Poison-Nernst
      Planck equations and compared with results obtained from stochastic Monte Carlo
      simulations.

PMID- 29024460
TI  - Reducing Readmissions: Nurse-Driven Interventions in the Transition of Care From
      the Hospital.
AB  - BACKGROUND: Transitions of care (TOC) from hospitals is a continuing focus for
      quality improvement to reduce readmissions. Sufficient resources to offer
      interventions remain an issue for hospitals, leading to efforts to target high
      risk patients and identify effective interventions. OBJECTIVES: Describe and
      measure effects, hospital-wide and among high-risk patients, of a multifaceted
      TOC program on 30-day readmissions in a 441-bed acute care community hospital.
      METHODS: Pre-post TOC intervention examining 30-day readmission rates during
      planning, implementation, and intervention years compared to baseline. Patient
      characteristics and services received by patients targeted for TOC individualized
      interventions during hospitalization and after discharge were retrieved from
      medical records and compared over 4 years during which the intervention was
      planned and implemented. RESULTS: Summary hospital-wide readmission rates reduced
      from 11.8% during planning (2011), 12.0% during implementation (2012), to 11.4%
      during intervention (2013) compared to 13.7% at prestudy baseline (2010; p <
      .001). TOC program patients were mostly identified by clinician referral (66.7%)
      rather than computer-generated risk at admission (32.3%), and nearly one-third
      (30.6%) were readmitted within 30 days of release. LINKING EVIDENCE TO ACTION:
      Reductions in readmissions were achieved using a multifaceted approach with
      efforts at admission, predischarge, and postdischarge in a community hospital.
      Having clinical staff involved in TOC program is important in both patient
      identification and interventions to reduce readmissions.

PMID- 29024462
TI  - Attitudes to personality disorder of staff working in high-security and medium
      security hospitals.
AB  - The discourse surrounding personality disorder is largely negative, and the
      diagnosis is considered to be associated with a degree of stigma. This study
      aimed to investigate staff attitudes towards personality disorder in high
      security and medium-security forensic-psychiatric hospitals in the UK. The
      Attitude to Personality Disorder Questionnaire was completed by 132 participants
      who were all current employees with clinical roles. Staff attitudes to
      personality disorder in the current study were significantly less positive than
      in comparable studies in similar settings. Having completed staff training
      surrounding personality disorder and being from a non-nursing professional
      background were the best predictors of positive attitudes to personality
      disorder. The findings of this study offer support to the pursuit of improving
      access to training in personality disorder for those working with this clinical
      presentation. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 29024461
TI  - Reproducible diagnosis of chronic lymphocytic leukemia by flow cytometry: An
      European Research Initiative on CLL (ERIC) & European Society for Clinical Cell
      Analysis (ESCCA) Harmonisation project.
AB  - The diagnostic criteria for CLL rely on morphology and immunophenotype. Current
      approaches have limitations affecting reproducibility and there is no consensus
      on the role of new markers. The aim of this project was to identify reproducible
      criteria and consensus on markers recommended for the diagnosis of CLL.
      ERIC/ESCCA members classified 14 of 35 potential markers as "required" or
      "recommended" for CLL diagnosis, consensus being defined as >75% and >50%
      agreement, respectively. An approach to validate "required" markers using normal
      peripheral blood was developed. Responses were received from 150 participants
      with a diagnostic workload >20 CLL cases per week in 23/150 (15%), 5-20 in 82/150
      (55%), and <5 cases per week in 45/150 (30%). The consensus for "required"
      diagnostic markers included: CD19, CD5, CD20, CD23, Kappa, and Lambda.
      "Recommended" markers potentially useful for differential diagnosis were: CD43,
      CD79b, CD81, CD200, CD10, and ROR1. Reproducible criteria for component reagents
      were assessed retrospectively in 14,643 cases from 13 different centers and
      showed >97% concordance with current approaches. A pilot study to validate
      staining quality was completed in 11 centers. Markers considered as "required"
      for the diagnosis of CLL by the participants in this study (CD19, CD5, CD20,
      CD23, Kappa, and Lambda) are consistent with current diagnostic criteria and
      practice. Importantly, a reproducible approach to validate and apply these
      markers in individual laboratories has been identified. Finally, a consensus
      "recommended" panel of markers to refine diagnosis in borderline cases (CD43,
      CD79b, CD81, CD200, CD10, and ROR1) has been defined and will be prospectively
      evaluated. (c) 2017 International Clinical Cytometry Society.

PMID- 29024463
TI  - IChem: A Versatile Toolkit for Detecting, Comparing, and Predicting Protein
      Ligand Interactions.
AB  - Structure-based ligand design requires an exact description of the topology of
      molecular entities under scrutiny. IChem is a software package that reflects the
      many contributions of our research group in this area over the last decade. It
      facilitates and automates many tasks (e.g., ligand/cofactor atom typing,
      identification of key water molecules) usually left to the modeler's choice. It
      therefore permits the detection of molecular interactions between two molecules
      in a very precise and flexible manner. Moreover, IChem enables the conversion of
      intricate three-dimensional (3D) molecular objects into simple representations
      (fingerprints, graphs) that facilitate knowledge acquisition at very high
      throughput. The toolkit is an ideal companion for setting up and performing many
      structure-based design computations.

PMID- 29024464
TI  - Influence of lipophilicity in O-acyl and O-alkyl derivatives of juglone and
      lawsone: a structure-activity relationship study in the search for natural
      herbicide models.
AB  - BACKGROUND: Naphthoquinones are known for their broad range of biological
      activities. Given the increasing demands of consumers in relation to food quality
      and growing concerns about the impact of synthetic herbicides, it is necessary to
      search for new agrochemicals. Natural products and allelopathy provide new
      alternatives for the development of pesticides with lower toxicity and greater
      environmental compatibility. RESULTS: A structure-activity relationship to
      evaluate the effect of bioavailability was performed. A total of 44 O-acyl and O
      alkyl derivatives of juglone and lawsone with different linear chain lengths were
      prepared. These compounds were tested on etiolated wheat coleoptiles, standard
      target species (STS) and four weeds, Echinochloa crus-galli L., Lolium rigidum
      Gaud., Lolium perenne L. and Avena fatua L. The results showed a strong influence
      of lipophilicity and, in most cases, the data fitted a logP-dependent quadratic
      mathematical model. CONCLUSION: The effects produced were mostly stunting and
      necrosis caused by growth inhibition. The potential structure and activity
      behaviour is described. (c) 2017 Society of Chemical Industry.

PMID- 29024465
TI  - Active Sites Intercalated Ultrathin Carbon Sheath on Nanowire Arrays as
      Integrated Core-Shell Architecture: Highly Efficient and Durable Electrocatalysts
      for Overall Water Splitting.
AB  - The development of active bifunctional electrocatalysts with low cost and earth
      abundance toward oxygen evolution reaction (OER) and hydrogen evolution reaction
      (HER) remains a great challenge for overall water splitting. Herein, metallic Ni4
      Mo nanoalloys are firstly implanted on the surface of NiMoOx nanowires array
      (NiMo/NiMoOx ) as metal/metal oxides hybrid. Inspired by the superiority of
      carbon conductivity, an ultrathin nitrogen-doped carbon sheath intercalated
      NiMo/NiMoOx (NC/NiMo/NiMoOx ) nanowires as integrated core-shell architecture are
      constructed. The integrated NC/NiMo/NiMoOx array exhibits an overpotential of 29
      mV at 10 mA cm-2 and a low Tafel slope of 46 mV dec-1 for HER due to the abundant
      active sites, fast electron transport, low charge-transfer resistance, unique
      architectural structure and synergistic effect of carbon sheath, nanoalloys, and
      oxides. Moreover, as OER catalysts, the NC/NiMo/NiMoOx hybrids require an
      overpotential of 284 mV at 10 mA cm-2 . More importantly, the NC/NiMo/NiMoOx
      array as a highly active and stable electrocatalyst approaches ~10 mA cm-2 at a
      voltage of 1.57 V, opening an avenue to the rational design and fabrication of
      the promising electrode materials with architecture structures toward the
      electrochemical energy storage and conversion.

PMID- 29024469
TI  - Noninvasive follicular thyroid neoplasm with papillary-like nuclear features in
      the pediatric age group.
AB  - BACKGROUND: The most common malignant thyroid neoplasm in children is papillary
      thyroid carcinoma (PTC). In 2015, the Endocrine Pathology Society introduced the
      terminology "noninvasive follicular thyroid neoplasm with papillary-like nuclear
      features" (NIFTP) to replace the noninvasive follicular variant of PTC. The
      objective of the current study was to evaluate previously diagnosed PTC in the
      pediatric population, reappraise it for NIFTP, and discuss the impact of NIFTP on
      the risk of malignancy (ROM) for each The Bethesda System for Reporting Thyroid
      Cytopathology category in the pediatric population. METHODS: The electronic
      databases of both study institutions were searched for all thyroidectomy
      specimens in patients aged <19 years from June 1, 2001 through June 1, 2016. The
      patient's age, sex, diagnosis, previous fine-needle aspiration cytology
      diagnosis, and follow-up were tabulated. Slides for available cases were reviewed
      and cases qualifying as NIFTP were separated. RESULTS: The cohort included 101
      resected nodules; cytological diagnoses were available for 95 cases. These cases
      included diagnoses of nondiagnostic (5 cases; 5.2%), benign (21 cases; 22.1%),
      atypia/follicular lesion of undetermined significance (9 cases; 9.5%), follicular
      neoplasm/suspicious for follicular neoplasm (FN/SFN) (25 cases; 26.3%),
      suspicious for malignancy (7 cases; 7.4%), and malignant (28 cases; 29.5%). On
      the histological follow-up, 50 cases (49.5%) were benign, 49 cases (48.5%) were
      malignant, and 2 cases (1.9%) were NIFTP. These NIFTP cases originally were
      diagnosed as FNs on fine-needle aspiration cytology. The average ROM for FNs with
      and without NIFTPs was 28% and 25%, respectively CONCLUSIONS: According to our
      rate of 1.9% for NIFTPs on reappraisal for resected nodules, this entity is
      likely to be less frequent in the pediatric population due to the higher
      prevalence of PTCs and/or more aggressive variants. NIFTPs do not appear to
      affect the ROM for The Bethesda System for Reporting Thyroid Cytopathology
      categories in the pediatric population. However, large-scale studies are
      necessary to determine whether NIFTPs could affect the pediatric population.
      Cancer Cytopathol 2018;126:27-35. (c) 2017 American Cancer Society.

PMID- 29024470
TI  - Predictive Validity of Radiographic Trabecular Bone Texture in Knee
      Osteoarthritis: The Osteoarthritis Research Society International/Foundation for
      the National Institutes of Health Osteoarthritis Biomarkers Consortium.
AB  - OBJECTIVE: To evaluate radiographic subchondral trabecular bone texture (TBT) as
      a predictor of clinically relevant osteoarthritis (OA) progression (combination
      of symptom and structural worsening). METHODS: The Foundation for the National
      Institutes of Health (FNIH) OA Biomarkers Consortium undertook a study of
      progressive knee OA cases (n = 194 knees with both radiographic and pain
      progression over 24-48 months) and comparators (n = 406 OA knees not meeting the
      case definition). TBT parameters were extracted from a medial subchondral tibial
      region of interest by fractal signature analysis of radiographs using validated
      semiautomated software. Baseline TBT and time-integrated values over 12 and 24
      months were evaluated for association with case status and separately with
      radiographic and pain progression status, adjusted for age, sex, body mass index,
      race, baseline Kellgren/Lawrence grade, baseline joint space width, Western
      Ontario and McMaster Universities Osteoarthritis Index pain score, and pain
      medication use. C statistics were generated from receiver operating
      characteristic curves. RESULTS: Relative to comparators, cases were characterized
      by thinner vertical and thicker horizontal trabeculae. The summed composite of 3
      TBT parameters at baseline and over 12 and 24 months best predicted case status
      (odds ratios 1.24-1.43). The C statistic for predicting case status using the TBT
      composite score (0.633-0.649) was improved modestly but statistically
      significantly over the use of covariates alone (0.608). One TBT parameter,
      reflecting thickened horizontal trabeculae in cases, at baseline and over 12 and
      24 months, predicted risk of any progression (radiographic and/or pain
      progression). CONCLUSION: Although associations are modest, TBT could be an
      attractive means of enriching OA trials for progressors since it can be generated
      from screening knee radiographs already standard in knee OA clinical trials.

PMID- 29024473
TI  - Building Sustainable Careers in Nursing Science: Scientific Innovations and
      Transdisciplinary Collaborations.

PMID- 29024471
TI  - PD-L1 expression in non-small cell lung carcinoma: Comparison among cytology,
      small biopsy, and surgical resection specimens.
AB  - BACKGROUND: One immunotherapeutic agent for patients with advanced non-small cell
      lung carcinoma, pembrolizumab, has a companion immunohistochemistry (IHC)-based
      assay that predicts response by quantifying programmed death-ligand 1 (PD-L1)
      expression. The current study assessed the feasibility of quantifying PD-L1
      expression using cytologic non-small cell lung carcinoma specimens and compared
      the results with those from small biopsy and surgical resection specimens.
      METHODS: PD-L1 expression was quantified using the IHC-based 22C3 pharmDx assay,
      with "positivity" defined as staining in >=50% viable tumor cells; >= 100 tumor
      cells were required for test adequacy. For cytology specimens, IHC was performed
      on cell block sections. RESULTS: A total of 214 specimens were collected from 188
      patients, 206 of which (96%) were found to be adequately cellular, including 36
      of 40 cytology (90%) and 69 of 72 small biopsy (96%) specimens. There was no
      significant difference noted with regard to the feasibility of PD-L1 IHC on small
      biopsy specimens compared with surgical resection specimens (P = .99), or between
      the percentage of PD-L1-positive cytology and histology (including surgical
      resection and histologic small biopsy) specimens (P = .083). PD-L1 expression was
      found to be concordant among samples from 21 of 23 patients from whom > 1
      specimen was collected (91%). There also was no significant difference observed
      with regard to rates of PD-L1 positivity when comparing age, sex, diagnosis, and
      specimen site. CONCLUSIONS: Quantification of PD-L1 expression is feasible on
      cytology specimens, and the results are comparable to those obtained from
      surgical resection and small biopsy specimens, including in matched specimens and
      using a single predictive IHC marker. Future studies will be necessary to
      determine the comparative value of other antibodies and their ability to predict
      response to immunotherapy. Cancer Cytopathol 2017;125:896-907. (c) 2017 American
      Cancer Society.

PMID- 29024472
TI  - Hearing crosstalk: the molecular conversation orchestrating inner ear
      dorsoventral patterning.
AB  - The inner ear is a structurally and functionally complex organ that functions in
      balance and hearing. It originates during neurulation as a localized thickened
      region of rostral ectoderm termed the otic placode, which lies adjacent to the
      developing caudal hindbrain. Shortly after the otic placode forms, it invaginates
      to delineate the otic cup, which quickly pinches off of the surface ectoderm to
      form a hollow spherical vesicle called the otocyst; the latter gives rise
      dorsally to inner ear vestibular components and ventrally to its auditory
      component. Morphogenesis of the otocyst is regulated by secreted proteins, such
      as WNTs, BMPs, and SHH, which determine its dorsoventral polarity to define
      vestibular and cochlear structures and sensory and nonsensory cell fates. In this
      review, we focus on the crosstalk that occurs among three families of secreted
      molecules to progressively polarize and pattern the developing otocyst. WIREs Dev
      Biol 2018, 7:e302. doi: 10.1002/wdev.302 This article is categorized under:
      Establishment of Spatial and Temporal Patterns > Gradients Signaling Pathways >
      Cell Fate Signaling Vertebrate Organogenesis > From a Tubular Primordium: Non
      Branched.

PMID- 29024474
TI  - Heart failure following blood cancer therapy in pediatric and adult populations.
AB  - AIM: The link between chemotherapy treatment and cardiotoxicity is well
      established, particularly for adults with blood cancers. However, it is less
      clear for children. This analysis aimed to compare the trajectory and mortality
      of children and adults who received chemotherapy for blood cancers and were
      subsequently hospitalized for heart failure. METHODS: Linked data from the
      Queensland Cancer Registry, Death Registry and Hospital Administration records
      for initial chemotherapy and later heart failure were reviewed (1996-2009). Of
      all identified blood cancer patients (N = 23 434), 8339 received chemotherapy,
      including 817 children (aged <=18 years at time of cancer diagnosis) and 7522
      adults. Time-varying Cox proportional hazards regression models were used to
      compare the characteristics and survival between the two groups. RESULTS: Of
      those who were subsequently hospitalized for heart failure, 70% of children and
      46% of adults had the index admission within 12 months of their cancer diagnosis.
      Of these, 53% of the pediatric heart failure population and 71% of the adult
      heart failure population died within the study period. Following adjustment for
      age, sex and chemotherapy admissions, children with heart failure had an
      increased mortality risk compared to their non-heart failure counterparts, a
      difference which was much greater than that between the adult groups. CONCLUSION:
      The impact of heart failure on children previously treated for blood cancer is
      more severe than for adults, with earlier morbidity and greater mortality.
      Improved strategies are needed for the prevention and management of
      cardiotoxicity in this population.

PMID- 29024476
TI  - Prevalence and outcomes of cystic lesions of the transplant pancreas: The
      University of Wisconsin Experience.
AB  - Literature on the behavior of cystic lesions in pancreas transplants is scarce,
      and hence a better understanding is warranted. Data on recipients and their
      respective donors that underwent simultaneous kidney and pancreas, pancreas
      transplant alone, and pancreas after kidney between 1994 and 2015 were reviewed
      (n = 1185). Cystic lesions of the transplant pancreas developed in 22 patients
      (1.8%): 12 pseudocysts, 2 cysts/remnants, 4 intraductal papillary mucinous
      neoplasms (IPMN), 2 adenocarcinomas, 1 low-grade intraepithelial pancreatic
      neoplasia, and 1 case of polycystic kidney disease. The median size was 3.6 cm
      (1.6-5.5 cm), and occurred at a median time of 65.5 months (2-183 months)
      posttransplant. The median age of the graft at time of diagnosis was 42 years
      (25.7-54.5), with 17 of 22 grafts (77%) functioning at time of diagnosis.
      Triggers for investigation were elevations in pancreatic enzymes, re-admissions
      for abdominal pain, and incidentalomas. High-resolution imaging and diagnostic
      biopsy/aspiration with ancillary tests were the main diagnostic tests. Most
      pseudocysts were managed by percutaneous drainage, and although no firm inference
      can be made from such a small series, we have observed that the behavior and
      management of IPMN and adenocarcinoma in the pancreas graft appears congruent to
      that of the native pancreas.

PMID- 29024477
TI  - T-Nb2 O5 /C Nanofibers Prepared through Electrospinning with Prolonged Cycle
      Durability for High-Rate Sodium-Ion Batteries Induced by Pseudocapacitance.
AB  - Homogeneous ultrasmall T-Nb2 O5 nanocrystallites encapsulated in 1D carbon
      nanofibers (T-Nb2 O5 /CNFs) are prepared through electrospinning followed by
      subsequent pyrolysis treatment. In a Na half-cell configuration, the obtained T
      Nb2 O5 /CNFs with the merits of unique microstructures and inherent
      pseudocapacitance, deliver a stable capacity of 150 mAh g-1 at 1 A g-1 over 5000
      cycles. Even at an ultrahigh charge-discharge rate of 8 A g-1 , a high reversible
      capacity of 97 mAh g-1 is still achieved. By means of kinetic analysis, it is
      demonstrated that the larger ratio of surface Faradaic reactions of Nb2 O5 at
      high rates is the major factor to achieve excellent rate performance. The
      prolonged cycle durability and excellent rate performance endows T-Nb2 O5 /CNFs
      with potentials as anode materials for sodium-ion batteries.

PMID- 29024475
TI  - Bioengineered lungs generated from human iPSCs-derived epithelial cells on native
      extracellular matrix.
AB  - The development of an alternative source for donor lungs would change the
      paradigm of lung transplantation. Recent studies have demonstrated the potential
      feasibility of using decellularized lungs as scaffolds for lung tissue
      regeneration and subsequent implantation. However, finding a reliable cell source
      and the ability to scale up for recellularization of the lung scaffold still
      remain significant challenges. To explore the possibility of regeneration of
      human lung tissue from stem cells in vitro, populations of lung progenitor cells
      were generated from human iPSCs. To explore the feasibility of producing
      engineered lungs from stem cells, we repopulated decellularized human lung and
      rat lungs with iPSC-derived epithelial progenitor cells. The iPSCs-derived
      epithelial progenitor cells lined the decellularized human lung and expressed
      most of the epithelial markers when were cultured in a lung bioreactor system. In
      decellularized rat lungs, these human-derived cells attach and proliferate in a
      manner similar to what was observed in the decellularized human lung. Our results
      suggest that repopulation of lung matrix with iPSC-derived lung epithelial cells
      may be a viable strategy for human lung regeneration and represents an important
      early step toward translation of this technology.

PMID- 29024478
TI  - High Relaxivity Gadolinium-Polydopamine Nanoparticles.
AB  - This study reports the preparation of a series of gadolinium-polydopamine
      nanoparticles (GdPD-NPs) with tunable metal loadings. GdPD-NPs are analyzed by
      nuclear magnetic relaxation dispersion and with a 7-tesla (T) magnetic resonance
      imaging (MRI) scanner. A relaxivity of 75 and 10.3 mM-1 s-1 at 1.4 and 7 T is
      observed, respectively. Furthermore, superconducting quantum interference device
      magnetometry is used to study intraparticle magnetic interactions and determine
      the GdPD-NPs consist of isolated metal ions even at maximum metal loadings. From
      these data, it is concluded that the observed high relaxivities arise from a high
      hydration state of the Gd(III) at the particle surface, fast rate of water
      exchange, and negligible antiferromagnetic coupling between Gd(III) centers
      throughout the particles. This study highlights design parameters and a robust
      synthetic approach that aid in the development of this scaffold for T1 -weighted,
      high relaxivity MRI contrast agents.

PMID- 29024479
TI  - Partite hallux sesamoid bones: Relationship with sesamoid bones at other
      metatarsophalangeal joints.
AB  - Partite hallux sesamoids are clinically meaningful but their association with
      other sesamoids is not clear. The objective was to relate the prevalence of the
      partite hallux sesamoid bones to sesamoid bones at other metatarsophalangeal
      (MTP) joints. We conducted a retrospective review of plain radiographs of 7946
      adult feet between November 2005 and September 2012 to identify partite hallux
      sesamoids and sesamoids at other MTP joints. Coexistence patterns of the
      partition and extra sesamoids were studied. Presence or absence of sesamoids at
      other MTP joints as well as sex and laterality were compared between the feet
      with and without partite hallux sesamoids using Pearson Chi-square test.
      Association between age and partition was evaluated using Spearman's correlation
      coefficient. Overall partite prevalence rate is 6.82%, and coexistence with extra
      MTP sesamoids was 0.42%. One pattern was partition in hallux sesamoid only, and 4
      patterns were coexistence with extra sesamoids. The prevalence rates of partite
      hallux sesamoids were 7.17% (508/7081) and 3.93% (34/865) in feet without and
      with extra sesamoids, respectively. The relative risk of 1.889 (95% CI, 1.325
      2.693) of partite hallux sesamoids was noted in feet without than with extra
      sesamoids (Chi2 = 12.759, P < 0.001). A negative correlation between age and
      distribution of partition was identified (r = -0.061, P < 0.001). Partition of
      hallux sesamoid bones is a developmental variation, it can coexist with sesamoids
      at other MTP joints following a certain pattern; and its prevalence rate is
      almost twice higher in feet without than with extra MTP sesamoids. Anat Rec,
      2017. (c) 2017 Wiley Periodicals, Inc. Anat Rec, 301:34-38, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29024480
TI  - Osmotic gradient ektacytometry: A valuable screening test for hereditary
      spherocytosis and other red blood cell membrane disorders.
AB  - INTRODUCTION: New generation osmotic gradient ektacytometry has become a powerful
      procedure for measuring red blood cell deformability and therefore for the
      diagnosis of red blood cell membrane disorders. In this study, we aim to provide
      further support to the usefulness of osmotic gradient ektacytometry for the
      differential diagnosis of hereditary spherocytosis by measuring the optimal
      cutoff values of the parameters provided by this technique. METHODS: A total of
      65 cases of hereditary spherocytosis, 7 hereditary elliptocytosis, 3 hereditary
      xerocytosis, and 171 normal controls were analyzed with osmotic gradient
      ektacytometry in addition to the routine red blood cell laboratory techniques.
      The most robust osmoscan parameters for hereditary spherocytosis diagnosis were
      determined using receiver operating characteristic curve analysis. RESULTS: The
      best diagnostic criteria for hereditary spherocytosis were the combination of
      decreased minimal elongation index up to 3% and increased minimal osmolality
      point up to 5.2% when compared to the mean of controls. Using this established
      criterion, osmotic gradient ektacytometry reported a sensitivity of 93.85% and a
      specificity of 98.38% for the diagnosis of hereditary spherocytosis. CONCLUSION:
      Osmotic gradient ektacytometry is an effective diagnostic test for hereditary
      spherocytosis and enables its differential diagnosis with other red blood cell
      membrane diseases based on specific pathology profiles.

PMID- 29024483
TI  - Neuromodulation: The "Not-so-Hidden" Cure for the Opioid Crisis.

PMID- 29024481
TI  - Late leakage after anterior resection: a defunctioning stoma alters the clinical
      course of anastomotic leakage.
AB  - AIM: Anastomotic leakage (AL) is common after anterior resection (AR). Long term
      clinical outcomes of AL including late presenting leakage (LL) are not well
      studied. This study was undertaken to assess clinical features of LL with respect
      to incidence, association with predisposing factors and need for re-intervention.
      METHODS: The Swedish Colorectal Cancer Registry (SCRCR) was explored for AL cases
      after AR for rectal cancer in patients operated in the south of Sweden from 1
      January 2001 to 31 December 2011. Demographic data, surgical technical details,
      number of postoperative days (POD) until diagnosis of AL, presenting symptoms,
      methods of diagnosis and treatment were retrieved from medical records. LL was
      defined according to different cut-offs as leakages occurring after hospital
      discharge (LLAHD), after 30 POD (LL >= POD 30) and after 90 POD (LL >= POD 90).
      RESULTS: In total, 1442 patients were operated on with AR of whom 144 cases of AL
      (10%) were identified. Median time from operation to follow-up was 87 months
      (range 21-162). LLAHD, LL >= POD 30 and LL >= POD 90 were present in 51%, 24% and
      9% respectively. All categories of LL were associated with a defunctioning stoma.
      Relaparotomy was significantly less often employed in LLAHD, but not in other
      categories of LL. CONCLUSION: LL constitutes a substantial portion of all AL
      after AR for rectal cancer. The large proportion of LLAHD calls for awareness in
      the outpatient setting.

PMID- 29024484
TI  - Through the Looking Glass: Specialty Influence on SCS Outcomes.

PMID- 29024485
TI  - Placenta-Derived Adherent Stromal Cells Improve Diabetes Mellitus-Associated Left
      Ventricular Diastolic Performance.
AB  - Left ventricular (LV) diastolic dysfunction is among others attributed to
      cardiomyocyte stiffness. Mesenchymal stromal cells (MSC) have cardiac-protective
      properties. We explored whether intravenous (i.v.) application of PLacenta
      eXpanded (PLX) MSC-like cells (PLX) improves LV diastolic relaxation in
      streptozotocin (STZ)-induced diabetic mice and investigated underlying
      mechanisms. Diabetes mellitus was induced by STZ application (50 mg/kg body
      weight) during five subsequent days. One week after the first STZ injection, PLX
      or saline were i.v. applied. Two weeks later, mice were hemodynamically
      characterized and sacrificed. At this early stage of diabetic cardiomyopathy with
      low-grade inflammation and no cardiac fibrosis, PLX reduced LV vascular cell
      adhesion molecule-1, transforming growth factor-beta1, and interferon-gamma mRNA
      expression, induced the percentage of circulating regulatory T cells, and
      decreased the splenic pro-fibrotic potential in STZ mice. STZ + PLX mice
      exhibited higher LV vascular endothelial growth factor mRNA expression and
      arteriole density versus STZ mice. In vitro, hyperglycemic PLX conditioned medium
      restored the hyperglycemia-impaired tube formation and adhesion capacity of human
      umbelical vein endothelial cells (HUVEC) via increasing nitric oxide (NO)
      bioavailability. PLX further induced the diabetes-downregulated activity of the
      NO downstream protein kinase G, as well as of protein kinase A, in STZ mice,
      which was associated with a raise in phosphorylation of the titin isoforms N2BA
      and N2B. Concomitantly, the passive force was lower in single isolated
      cardiomyocytes from STZ + PLX versus from STZ mice, which led to an improvement
      of LV diastolic relaxation. We conclude that i.v. PLX injection improves diabetes
      mellitus-associated diastolic performance via decreasing cardiomyocyte stiffness.
      Stem Cells Translational Medicine 2017;6:2135-2145.

PMID- 29024486
TI  - Development of locus specific sub-clone separation by fluorescence in situ
      hybridization in suspension in chronic lymphocytic leukemia.
AB  - Intra-tumor genetic heterogeneity is a hallmark of cancer. The ability to monitor
      and analyze these sub-clonal cell populations can be considered key to successful
      treatment, particularly in the modern era of targeted therapies. Although
      advances in sequencing technologies have significantly improved our ability to
      analyze the mutational landscape of tumors, this utility is reduced when
      considering small, but clinically significant sub-clones, that is, those
      representing <10% of the tumor burden. We have developed a high-throughput method
      that utilizes a 17-probe labeled bacterial artificial chromosome contig to
      quantify sub-clonal populations of cells based on deletion of a single locus.
      Chronic lymphocytic leukemia (CLL) cells harboring deletion of the short arm of
      chromosome 17 (del17p), an important prognostic marker for CLL were used to
      demonstrate the technique. Sub-clones of del17p cells were quantified and
      isolated from heterogeneous CLL populations using fluorescence in situ
      hybridization in suspension (FISH-IS) and the locus specific probe set. Using the
      combination of FISH-IS with the locus-specific probe set enables automated
      analysis of tens of thousands of cells, accurately quantifying and isolating
      cells carrying a del17p. Based on the fluorescence intensity of 17p probes, 17p
      (TP53) deleted cells were identified and sorted using flow cytometric techniques,
      and enrichment was demonstrated using single nucleotide polymorphism analysis.
      The ability to separate sub-clones of cells based on genetic heterogeneity,
      independent of the clone size, highlights the potential application of this
      method not only in the diagnostic and prognostic setting, but also as an unbiased
      approach to enable further detailed genetic analysis of the sub-clone with deep
      sequencing approaches. (c) 2017 International Society for Advancement of
      Cytometry.

PMID- 29024488
TI  - Maternal Use of Weight Loss Products and the Risk of Neural Tube Defects in
      Offspring: A Systematic Literature Review.
AB  - BACKGROUND: Several studies have assessed potential associations between use of
      weight loss products in the periconceptional period and neural tube defects
      (NTDs). However, the individual studies are inconclusive and there has not been a
      systematic review of this literature. METHODS: We conducted a systematic search,
      using Ovid MEDLINE and PubMed, to identify studies that evaluated the association
      between products used for weight loss and the risk of NTDs. Because many studies
      of birth defects only evaluate a composite birth defect outcome, we evaluated
      studies that defined the outcome as "any major birth defect" or as NTDs. We
      abstracted data on study design, exposure definition, outcome definition,
      covariates and effect size estimates from each article that met our inclusion
      criteria. For studies that evaluated a composite birth defect outcome, we also
      abstracted the number of NTD cases included in the composite outcome. We used a
      modified version of the Newcastle-Ottawa Scale to assess the quality of each
      article. RESULTS: We screened 865 citations and identified nine articles that met
      our inclusion criteria. The majority of studies reported positive associations
      between maternal use of weight loss products and birth defects (overall and
      NTDs). However, there were few significant associations and there was
      considerable heterogeneity in the specific exposures assessed across the nine
      studies. CONCLUSION: Our systematic review of weight loss products and NTDs
      indicates that the literature on this topic is sparse. Because several studies
      reported modest, positive associations between risk and use of weight loss
      products, additional studies are warranted. Birth Defects Research 110:48-55,
      2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29024487
TI  - Controlling the Release of Small, Bioactive Proteins via Dual Mechanisms with
      Therapeutic Potential.
AB  - Injectable delivery systems that respond to biologically relevant stimuli present
      an attractive strategy for tailorable drug release. Here, the design and
      synthesis of unique polymers are reported for the creation of hydrogels that are
      formed in situ and degrade in response to clinically relevant endogenous and
      exogenous stimuli, specifically reducing microenvironments and externally applied
      light. Hydrogels are formed with polyethylene glycol and heparin-based polymers
      using a Michael-type addition reaction. The resulting hydrogels are investigated
      for the local controlled release of low molecular weight proteins (e.g., growth
      factors and cytokines), which are of interest for regulating various cellular
      functions and fates in vivo yet remain difficult to deliver. Incorporation of
      reduction-sensitive linkages and light-degradable linkages affords significant
      changes in the release profiles of fibroblast growth factor-2 (FGF-2) in the
      presence of the reducing agent glutathione or light, respectively. The
      bioactivity of the released FGF-2 is comparable to pristine FGF-2, indicating the
      ability of these hydrogels to retain the bioactivity of cargo molecules during
      encapsulation and release. Further, in vivo studies demonstrate degradation
      mediated release of FGF-2. Overall, our studies demonstrate the potential of
      these unique stimuli-responsive chemistries for controlling the local release of
      low molecular weight proteins in response to clinically relevant stimuli.

PMID- 29024489
TI  - A novel combination regimen with intense focused ultrasound and pressure- and
      dose-controlled transcutaneous pneumatic injection of hypertonic glucose solution
      for lifting and tightening of the aging face.
AB  - BACKGROUND: Intense focused ultrasound (IFUS) has demonstrated moderate efficacy
      for facial laxity of the aging face. Pressure- and dose-controlled transcutaneous
      pneumatic injections of hypertonic glucose solution (TPIG) are a minimally
      invasive way to deliver solution into the skin for therapeutic purposes.
      Recently, its application around temporal areas is known to exert early-onset
      lifting effects with facial contour rejuvenation. AIMS: We sought to evaluate the
      safety and efficacy of this novel combination regimen with IFUS and TPIG for
      lifting and tightening of aging face. PATIENTS AND METHODS: Twenty-two Korean
      subjects with mild-to-moderate facial skin laxity were evaluated after receiving
      a sequential single session of IFUS and TPIG treatments. Dermatologists'
      objective assessments for general appearance, and mid- and low faces based on
      photographic images were performed at 1- and 12-week post-treatment follow-ups.
      Patients' subjective assessments were also conducted. Skin biopsies were taken at
      baseline and the last visit. RESULTS: Among 22 subjects, twenty (91%)
      demonstrated improvement after 12-week follow-up. We also observed similarly
      improved state just after 1 week of treatments (82%: 18/22). Specifically,
      improvement of the mid-face was evident from the first week, while the progress
      of the low face improvement was observed at the twelve week. Subjective
      assessments paralleled these findings. No seriously adverse effect was observed
      during procedures. Histologic evaluation showed greater dermal collagen fibers
      throughout the dermis after treatments. CONCLUSION: Combination treatment with
      IFUS and TPIG has beneficial effects for skin lifting and tightening with early
      onset time.

PMID- 29024490
TI  - Categorization of Abuse Potential-Related Adverse Events.
AB  - All drugs with central nervous system activity must undergo an assessment of
      their abuse potential, and these data must be included in a New Drug Application.
      Part of this assessment is an analysis of treatment-emergent adverse events that
      occur during clinical development. Using an iterative consensus strategy, we
      evaluated and grouped an available list of 213 flag terms for abuse potential
      from the Food and Drug Administration, into categories and assessed the relevance
      of the terms to primary abuse behavior. Consequences of abuse (28%) were most
      common, followed by diagnoses (19%), altered thoughts (18%), cognitive effects
      (10%), stimulation/anxiety (9%), central nervous system depression (9%), and mood
      elevation (1%). The vast majority of abuse potential-related terms reflects
      treatment-emergent adverse events, not behaviorally motivating features to abuse
      a drug. Almost 30% of terms are related to altered perception or altered
      cognition. These are serious consequences in the context of abusable psychoactive
      drugs. Only 20% of terms were rated as definitely or probably reflecting
      intrinsic behavioral reinforcing potential, and 30% were assessed as having weak
      predictive utility. Sponsors need to have an explicit strategy for collecting,
      interpreting, and analyzing abuse-related adverse event information completely
      and accurately.

PMID- 29024491
TI  - Surgical morbidity and mortality in patients after microvascular reconstruction
      for head and neck cancer.
AB  - OBJECTIVES: The aim was to evaluate the importance of clinical factors in the
      prediction of postoperative complications in patients with microvascular
      reconstruction for head and neck squamous cell cancer (HNSCC). DESIGN: A
      retrospective review of case notes was performed. SETTING: Patients treated at a
      single institute. PARTICIPANTS: This study included 259 patients with HNSCC
      treated with radical surgery and microvascular reconstruction between 1993 and
      2014. MAIN OUTCOME MEASURES: We allocated the patients to three groups using a
      preoperative comorbidity score based on risk factors: group A (>=3 risk factors,
      n = 16), group B (2 risk factors, n = 49) and group C (0 or 1 risk factor, n =
      194). RESULTS: Surgical mortality in this cohort was 1.9% (5 of 259 patients).
      The preoperative comorbidity score was associated with surgical mortality (P <
      .001). Pharyngocutaneous fistula (P = .001) and flap compromise (P = .023) were
      more frequent as preoperative comorbidity score increased. Preoperative
      comorbidity score (P < .001), advanced age (P = .007), advanced pathologic T
      stage (P = .028), advanced pathologic N stage (P = .005), preoperative (chemo)
      radiotherapy (P < .001), history of cardiovascular disease (P = .015) and
      pulmonary disease (P = .007), and diabetes (P < .001) had significant adverse
      effects on 5 year disease-specific survival (DSS) in a univariate analysis. The 5
      DSS rates of groups A, B and C were 30%, 37% and 70%, respectively. Multivariate
      analysis showed that preoperative comorbidity score was significantly correlated
      with 5 year DSS (hazard ratio [HR], 3.56; 95% confidence interval [CI], 1.81
      6.99; P < .001 for group A and HR, 1.91; 95% CI, 1.15-3.18; P = .013 for group B
      compared with group C). CONCLUSION: Patients with a high preoperative comorbidity
      score have an increased risk of surgical mortality and morbidity after
      microvascular reconstruction for HNSCC.

PMID- 29024492
TI  - Experimental infection of clade 1.1.2 (H5N1), clade 2.3.2.1c (H5N1) and clade
      2.3.4.4 (H5N6) highly pathogenic avian influenza viruses in dogs.
AB  - Since the emergence of highly pathogenic avian influenza (HPAI) H5N1 in Asia, the
      haemagglutinin (HA) gene of this virus lineage has continued to evolve in avian
      populations, and H5N1 lineage viruses now circulate concurrently worldwide. Dogs
      may act as an intermediate host, increasing the potential for zoonotic
      transmission of influenza viruses. Virus transmission and pathologic changes in
      HPAI clade 1.1.2 (H5N1)-, 2.3.2.1c (H5N1)- and 2.3.4.4 (H5N6)-infected dogs were
      investigated. Mild respiratory signs and antibody response were shown in dogs
      intranasally infected with the viruses. Lung histopathology showed lesions that
      were associated with moderate interstitial pneumonia in the infected dogs. In
      this study, HPAI H5N6 virus replication in dogs was demonstrated for the first
      time. Dogs have been suspected as a "mixing vessel" for reassortments between
      avian and human influenza viruses to occur. The replication of these three
      subtypes of the H5 lineage of HPAI viruses in dogs suggests that dogs could serve
      as intermediate hosts for avian-human influenza virus reassortment if they are
      also co-infected with human influenza viruses.

PMID- 29024494
TI  - Extensive hyperpigmentation of the face in a Filipina.

PMID- 29024493
TI  - Pharmacokinetics and Pharmacodynamics of Meloxicam in East Asian Populations: The
      Role of Ethnicity on Drug Response.
AB  - We aimed to reanalyze the differences in the pharmacokinetics (PKs) of meloxicam
      in East Asian populations based on a population approach using previously
      published data and to investigate the factors found in population PK analysis
      that affect the pharmacodynamics (PDs) of meloxicam. Population PK analysis was
      performed in 119 healthy male subjects (30 Japanese, 30 Chinese, 29 Korean, and
      30 white) under strictly controlled trial conditions with regulated meals and a
      single lot of the drug. We found that CYP2C9 genotype and lean body mass were
      statistically significant predictors of clearance and volume of distribution,
      respectively. A statistical significant difference in the PK parameters between
      ethnic groups could not be identified. Simulations using PK/PD models showed that
      CYP2C9 genotype is the factor that affects the PDs of meloxicam. The genetic
      polymorphisms highlighted in this study would be beneficial for conducting
      clinical trials in East Asians with similar genetic backgrounds.

PMID- 29024495
TI  - Differences in the neovascular potential of thymus versus subcutaneous adipose
      derived stem cells from patients with myocardial ischaemia.
AB  - Adipose tissue-derived multipotent mesenchymal cells (ASCs) participate in the
      information of blood vessels under hypoxic conditions. It is probable that the
      susceptibility of ASCs to the influence of age and ageing-associated pathologies
      compromises their therapeutic effectiveness depending on the adipose tissue
      depot. Our aim was to examine the neovascular potential under hypoxic conditions
      of ASCs-derived from thymic (thymASCs) and subcutaneous (subASCs) adipose tissue
      from 39 subjects with and without type 2 diabetes mellitus (T2DM) and of
      different ages who were undergoing coronary bypass surgery. We confirmed a
      significant decrease in the percentage of CD34+ CD31- CD45- subASCs in the cell
      yield of subASCs and in the survival of cultured endothelial cells in the medium
      conditioned by the hypox-subASCs with increasing patient age, which was not
      observed in thymASCs. Whereas the length of the tubules generated by hypox
      subASCs tended to correlate negatively with patient age, tubule formation
      capacity of the hypoxic thymASCs increased significantly. Compared with subASCs,
      thymASCs from subjects over age 65 and without T2DM showed higher cell yield,
      tubule formation capacity, vascular endothelial growth factor secretion levels,
      and ability to promote endothelial cell survival in their conditioned medium.
      Deterioration in subASCs neovascular potential relative to thymASCs derived from
      these subjects was accompanied by higher expression levels of NOX4 mRNA and
      fibrotic proteins. Our results indicate that thymASCs from patients over age 65
      and without T2DM have a higher angiogenic potential than those from the other
      patient groups, suggesting they may be a good candidate for angiogenic therapy in
      subjects undergoing coronary bypass surgery.

PMID- 29024496
TI  - Higher Levels of Cystatin C in HIV/AIDS Patients with Metabolic Syndrome.
AB  - Data about Cystatin-C levels in HIV-infected patients with metabolic syndrome
      (MetS) are still limited. Therefore, the aim of this study was to evaluate the
      possible correlations of serum levels of Cystatin-C in HIV/AIDS patients treated
      with combined antiretroviral therapy (cART) with or without MetS. This cross
      sectional study included 89 HIV/AIDS Caucasian patients receiving cART at the
      HIV/AIDS Centre Belgrade, Serbia, divided into two groups according to the
      presence of MetS. Cystatin-C and other biochemical parameters were measured using
      Cytokine-Array-I, Metabolic-Array-I and Metabolic-Array-II, at the Department of
      Clinical Biochemistry, Royal Free Hospital and University College London, UK. A
      linear regression model was performed to evaluate which clinical and laboratory
      variables had an independent effect on Cystatin-C levels in HIV/AIDS patients.
      There were 33 (37%) patients with MetS and 56 (63%) without MetS. Patients with
      and without MetS were homogenous for age, duration of cART, number of cART
      combinations and CD4+ T cell count. Statistically increased Cystatin-C levels
      were observed in HIV/AIDS patients with MetS (p = 0.017), when compared to
      patients without MetS. Data showed a positive correlation of Cystatin-C and C
      reactive protein (r = 0.349, p = 0.001). Using linear regression modelling,
      significant correlations were obtained between Cystatin-C and MetS in univariate
      analysis (p < 0.001). Cystatin-C levels were significantly higher in HIV/AIDS
      patients with MetS versus without MetS. Early assessment of MetS using Cystatin-C
      as a marker may ultimately help increase the lifespan of HIV/AIDS patients, as
      these patients appear to be at high risk of cardiovascular diseases.

PMID- 29024497
TI  - A mission-oriented approach to cancer in Europe: a joint mission/vision 2030.
AB  - By combining innovative prevention and treatment strategies in a sustainable
      state-of-the-art virtual European cancer centre/infrastructure, it will be
      possible by 2030 to achieve a long-term survival of 3 out of 4 cancer patients in
      countries with well-developed healthcare systems. Furthermore, the proposed
      concerted actions will pave the way to handling the economic and social
      inequalities in countries with less developed systems. These efforts will also
      ensure that in the long-run, science-driven and social innovations reach patients
      across the healthcare systems in Europe.

PMID- 29024498
TI  - Feasibility and efficiency of concurrent chemoradiotherapy with capecitabine and
      cisplatin versus radiotherapy alone for elderly patients with locally advanced
      esophageal squamous cell carcinoma: Experience of two centers.
AB  - BACKGROUND: The purpose of this retrospective study was to evaluate the
      feasibility and efficacy of definitive concurrent chemoradiotherapy (CCRT) with
      capecitabine and cisplatin for elderly patients with locally advanced esophageal
      squamous cell carcinoma. METHODS: A total of 90 patients were included from two
      different centers. Forty-nine patients were treated with CCRT consisting of
      capecitabine (850 mg/m2 , oral, twice a day for 1-14 days) and cisplatin (20
      mg/m2 ) weekly during radiotherapy (RT). The remaining 41 patients were treated
      with RT alone. The overall response, overall survival, progression-free survival,
      and toxicity rates were recorded. RESULTS: Compared to the RT group (51.2%; P =
      0.029), the overall response rate in the CCRT group (73.5%) was obviously higher.
      A complete response was achieved in 34.7% and 14.6% of patients in the CCRT and
      RT groups, respectively (P = 0.030). Median progression-free and median overall
      survival rates were significantly higher in the CCRT group (24.7 and 30.6 months;
      P < 0.05) compared to the RT group (16.6 and 18.7 months). Acute toxic effects
      were more severe in the CCRT group, but no significant difference in grade 3 or 4
      acute toxicities was observed between the groups. CONCLUSION: Both CCRT with
      capecitabine and cisplatin and RT alone are feasible to treat elderly patients
      and yield a good performance status with locally advanced esophageal squamous
      cell carcinoma. CCRT improved the tumor response without increasing the side
      effects compared to RT alone. CCRT is recommended for patients over 65 with good
      performance status.

PMID- 29024499
TI  - Male partner involvement on initiation and sustainment of exclusive breastfeeding
      among HIV-infected post-partum women: Study protocol for a randomized controlled
      trial.
AB  - Exclusive Breastfeeding (EBF) among human immunodeficiency virus (HIV)-infected
      mothers is known to be associated with a sustained and significant reduction in
      HIV transmission and has the potential to reduce infant and under-five mortality.
      Research shows that EBF is not common in many HIV-endemic, resource-limited
      settings despite recommendations by the World Health Organization. Although
      evidence abounds that male partner involvement increases HIV testing and uptake
      and retention of prevention of mother-to-child transmission interventions, few
      studies have evaluated the impact of male partners' involvement and decision
      making on initiation, maintenance, and sustainment of EBF. We propose a
      comparative effectiveness trial of Men's Club as intervention group compared to
      the control group on initiation and sustainment of EBF. Men's Club will provide
      male partners of HIV-infected pregnant women one 5-hr interactive educational
      intervention to increase knowledge on EBF and explore barriers and facilitators
      of EBF and support. Additionally, participating male partners in the Men's Club
      as intervention group will receive weekly text message reminders during the first
      6-week post-natal period to improve initiation and sustainment of EBF.
      Participants in the Men's Club as control group will receive only educational
      pamphlets. Primary outcomes are the differences in the rates of initiation and
      sustainment of EBF at 6 months between the two groups. Secondary outcomes are
      differences in male partner knowledge of infant feeding options and the intent to
      support EBF in the two groups. Understanding the role and impact of male partners
      on the EBF decision-making process will inform the development of effective and
      sustainable evidence-based interventions to support the initiation and
      sustainment of EBF.

PMID- 29024500
TI  - Tumor suppressive roles of eugenol in human lung cancer cells.
AB  - BACKGROUND: Eugenol, a natural compound available in Syzigium aromaticum
      (cloves), is exploited for various medicinal applications. Eugenol induces
      apoptosis and functions as an anti-cancer drug in several types of tumors. We
      investigated the tumor suppressive role and potential mechanisms of eugenol in
      human lung cancer cells. METHODS: Human embryonic lung fibroblast MRC-5 and lung
      cancer adenocarcinoma A549 cells were incubated with or without various
      concentrations of eugenol for 24 hours. Cell counting kit 8 and crystal violet
      staining assays were performed to detect cell viability. The cell migration and
      invasion abilities were also determined by wound healing and transwell assays.
      Finally, Western blotting assay was performed to examine the changes in lung
      cancer cell viability and invasion of downstream targets after treatment with
      eugenol. RESULTS: Eugenol could inhibit cell viability in lung cancer cells.
      Furthermore, eugenol obviously impaired cell migration and invasion. Finally, the
      expression levels of phosphate-Akt and MMP-2 in lung cancer cells were reduced
      after treatment with eugenol. CONCLUSION: Our results demonstrated the tumor
      suppressive roles of eugenol on lung cancer cell proliferation, migration, and
      invasion partially through the PI3K/Akt pathway and MMP activity in vitro. These
      results suggest eugenol as a potential chemotherapeutic agent against human lung
      cancer.

PMID- 29024502
TI  - Rhodium(III)-Catalyzed Directed C-H Amidation of N-Nitrosoanilines and Subsequent
      Formation of 1,2-Disubstituted Benzimidazoles.
AB  - An efficient rhodium-catalyzed direct C-H amidation of N-nitrosoanilines with
      1,4,2-dioxazol-5-ones as amidating agents has been developed. This method
      featured mild reaction conditions, a wide substrate scope and satisfactory
      yields. Besides, the amidated products could be readily converted to
      pharmaceutically valuable 1,2-disubstituted benzimidazoles via an HCl-mediated
      deprotection/cyclization process in one pot.

PMID- 29024501
TI  - Hemodialysis Decreases the Concentration of Accumulated Plant Phenols in the
      Plasma of Patients on Maintenance Dialysis: Influence of Residual Renal Function.
AB  - Plant phenols may accumulate in end-stage kidney disease. The effect of
      hemodialysis on their plasma concentration remains poorly determined. Contingent
      on concentration, health-promoting or noxious effects occur; therefore, we
      assessed plasma concentration in hemodialyzed patients. In total, 21 maintenance
      hemodialyzed patients with diuresis < 500 mL per day (with oliguria), nine
      hemodialyzed patients with diuresis >= 500 mL per day (without oliguria) and 31
      healthy volunteers were included. Nine phenolic acids were identified with high
      performance liquid chromatography and total polyphenol concentration was
      determined with the Folin-Ciocalteu method in pre- or post-hemodialysis plasma
      and pre- or intra-hemodialysis dialysate. The concentration of total polyphenols
      was 27% higher in pre-hemodialysis plasma than in that of controls (0.95 +/- 0.18
      mmol/L [P < 0.0001]). The concentration of total polyphenols was higher in
      patients with oliguria (1.01 +/- 0.17) than in those without (0.84 +/- 0.13
      mmol/L), despite the former having more intense hemodialysis (Kt/V 1.29 +/- 0.31
      and 0.77 +/- 0.25, respectively). Pre-hemodialysis phenolic acid concentration in
      patients undergoing dialysis exceeded reference values by 3 to 34 times (3
      hydroxyphenylacetic acid and vanillic acid, respectively), from 0.69
      (dihydrocaffeic acid) to 169.3 MUmol/L (hippuric acid). The concentration of six
      phenolic acids (3-hydroxyhippuric, caffeic, dihydrocaffeic, hippuric,
      homovanillic, and vanillic acid) was 1.1 (homovanillic) to 11.3 (3
      hydroxyhippuric) times higher in patients with oliguria than in those without. 4
      hydroxyhippuric acid occurred more in the plasma of patients with oliguria than
      in those without oliguria. A single hemodialysis session decreased total
      polyphenol concentration by 16% and phenolic acids from 30% (caffeic) to 58%
      (vanillic and 3-hydroxyphenylacetic acid) and these compounds appeared in the
      dialysate. The percentage decrease (Delta%) of creatinine concentration
      correlated with the Delta% of total polyphenols and five phenolic acids (3
      hydroxyphenylacetic, dihydrocaffeic, hippuric, homovanillic, and vanillic acid).
      Urea Delta% and Kt/V correlated only with the Delta% of homovanilic acid. The
      results demonstrate that phenols accumulate variably in hemodialyzed patients and
      are differently eliminated during hemodialysis. Residual renal function ensures a
      lower concentration of plasma phenols.

PMID- 29024503
TI  - Discovery of HLA-C*14:87, a novel HLA-C*14 variant, in a Taiwanese individual.
AB  - One nucleotide substitution at residue 526 of the HLA-C*14:15 results in a novel
      allele, HLA-C*14:87.

PMID- 29024504
TI  - High validity of cardiomyopathy diagnoses in western Sweden (1989-2009).
AB  - AIM: Hospital discharges with a diagnosis of cardiomyopathy have more than
      doubled in Sweden since 1987. We validated the cardiomyopathy diagnoses over this
      time period to investigate that the increase was real and not a result of
      improved recognition of the diagnosis and better diagnostic methods. METHODS AND
      RESULTS: Every fifth year from 1989 to 2009, records for all patients with a
      cardiomyopathy diagnosis were identified by searching the local registers in
      three hospitals in Vastra Gotaland, Sweden. The diagnoses were validated
      according to criteria defined by the European Society of Cardiology from 2008.
      The population comprised 611 cases with cardiomyopathy diagnoses [mean age 58.9
      (SD 15.5) years, 68.2% male], divided into three major groups: dilated,
      hypertrophic, and other cardiomyopathies. Hypertrophic cardiomyopathy and
      hypertrophic obstructive cardiomyopathy were analysed as a group.
      Cardiomyopathies for which there were few cases, such as restrictive,
      arrhythmogenic right ventricular, left ventricular non-compaction, takotsubo, and
      peripartum cardiomyopathies, were analysed together and defined as 'other
      cardiomyopathies'. Relevant co-morbidities were registered. The use of
      echocardiography was 99.7%, of which 94.6% was complete echocardiography reports.
      The accuracy rates of the diagnoses dilated cardiomyopathy, hypertrophic
      cardiomyopathy, and other cardiomyopathies were 85.5%, 87.5%, and 100%,
      respectively, with no differences between the three hospitals or years studied;
      nor did the prevalence of co-morbidities differ. CONCLUSIONS: The accuracy rate
      of the cardiomyopathy diagnoses from in-hospital records from >600 patients in
      western Sweden during a 20 year period was 86.6%, with no significant trend over
      time, strengthening epidemiological findings that this is likely due to an actual
      increase in cardiomyopathy diagnoses rather than changes in coding practices. The
      use of echocardiography was high, and there was no significant difference in co
      morbidities during the study period. The accuracy rate of the cardiomyopathy
      diagnoses during the 20 year period was high. The use of diagnostic tools did not
      increase under the study period, and once cardiomyopathy diagnoses were
      suspected, echocardiography was performed in almost all cases. In this study, the
      occurrence of cardiomyopathy was increasing over time without significant
      increase of co-morbidity, supporting that an actual increase of cardiomyopathy
      has occurred.

PMID- 29024505
TI  - Photoelectrochemical Complexes of Fucoxanthin-Chlorophyll Protein for Bio
      Photovoltaic Conversion with a High Open-Circuit Photovoltage.
AB  - Open-circuit photovoltage (Voc ) is among the critical parameters for achieving
      an efficient light-to-charge conversion in existing solar photovoltaic devices.
      Natural photosynthesis exploits light-harvesting chlorophyll (Chl) protein
      complexes to transfer sunlight energy efficiently. We describe the exploitation
      of photosynthetic fucoxanthin-chlorophyll protein (FCP) complexes for realizing
      photoelectrochemical cells with a high Voc . An antenna-dependent photocurrent
      response and a Voc up to 0.72 V are observed and demonstrated in the bio
      photovoltaic devices fabricated with photosynthetic FCP complexes and TiO2
      nanostructures. Such high Voc is determined by fucoxanthin in FCP complexes, and
      is rarely found in photoelectrochemical cells with other natural light-harvesting
      antenna. We think that the FCP-based bio-photovoltaic conversion will provide an
      opportunity to fabricate environmental benign photoelectrochemical cells with
      high Voc , and also help improve the understanding of the essential physics
      behind the light-to-charge conversion in photosynthetic complexes.

PMID- 29024506
TI  - A Near-Infrared Responsive Drug Sequential Release System for Better Eradicating
      Amyloid Aggregates.
AB  - Polyphenol compounds, such as curcumin, rutin, rifampicin, can inhibit Abeta
      aggregation and decrease reactive oxygen species (ROS), and have received much
      attention in recent years for Alzheimer's disease (AD) treatment. However, the
      excess metal ions in amyloid plaque can chelate to polyphenol compounds. It
      significantly declines the efficacy of polyphenol compounds when used in the
      clinic. In this report, a near-infrared (NIR)-caged upconversion responsive
      system UCNP@SiO2 @Cur/CQ is designed and synthesized to control drug sequential
      release by regulating NIR laser. When the system is irradiated at low intensity
      of the NIR laser, the caged metal chelator, clioquinol (CQ), is first released
      for removing free metal ions, which affects the efficacy of curcumin.
      Subsequently, the strongly caged curcumin is released with increasing the
      intensity of NIR light. In this way, the treatment efficacy of curcumin is
      improved. This NIR-caged drug release system can not only remove Cu2+ but also
      clean superfluous ROS. Therefore, developing controllable sequential drug
      releasing may provide clinical benefits of combination treatment of AD. To the
      best of our knowledge, this work reports for the first time that a sequentially
      controlled system can overcome the interference of metal ions on polyphenol
      compounds for AD treatment.

PMID- 29024507
TI  - Dietary patterns and semen quality: a systematic review and meta-analysis of
      observational studies.
AB  - A number of studies have examined the association between dietary patterns and
      semen quality, but the findings have been inconclusive. Herein, we conducted a
      systematic review and meta-analysis of observational studies to assess the
      association between dietary patterns and semen quality. PubMed, Cochrane library,
      Science direct, Scopus, Google Scholar, and ISI web of science databases were
      searched up to August 2016 for observational studies assessing the association
      between common dietary patterns and sperm quality markers. Data were pooled by
      the generic inverse variance method with random effects and expressed as mean
      differences with 95% confidence intervals (CIs). Heterogeneity was assessed
      (Cochrane Q-statistic) and quantified (I2 -statistic). The Newcastle-Ottawa Scale
      assessed study quality. Six eligible studies, involving 8207 participants, were
      included in our systematic review and meta-analysis. The pooled mean difference
      of sperm concentration for the healthy dietary pattern versus unhealthy dietary
      pattern intake was mean difference: 0.66; 95% CI, 0.305-1.016; p < 0.001. In
      comparison with those who had the highest adherence to healthy dietary pattern,
      individuals in the lowest adherence had significantly lower level of sperm
      concentration. However, no significant association was seen between eating
      patterns and other semen quality. Healthy dietary pattern seems to be associated
      with elevated sperm concentration level. Further longitudinal studies are needed
      to clarify this relationship.

PMID- 29024508
TI  - Importance of an Orchestrate Participation of each Individual Residue Present at
      a Catalytic Site.
AB  - GTP hydrolysis is indispensable to keep a living cell healthy. Nature has evolved
      so many enzymes to enhance the slow GTP hydrolysis. Rab GTPases are evolved to
      regulate vesicle trafficking. GTPase activating proteins (GAPs) accelerates their
      intrinsic slow GTP hydrolysis in order to maintain the sustainability between
      cellular events. Any malfunction/interference in this hydrolysis disrupts normal
      cellular events and causes severe diseases. In this study, GTP hydrolysis
      mechanism of Rab33B catalyzed by TBC-domain GAP protein Gyp1p has been decoded
      using extensive ab initio QM/MM metadynamics simulations. An organized coupled
      movement of individual residues present at the catalytic site is found to be the
      key factor for this reaction. An unorganized coupled movement leads the
      hydrolysis through very high energy pathways. This also reveals that the chemical
      transformations occurring at a catalytic site are residue specific.

PMID- 29024509
TI  - Adding a new separation dimension to MS and LC-MS: What is the utility of ion
      mobility spectrometry?
AB  - Ion mobility spectrometry is an analytical technique known for more than 100
      years, which entails separating ions in the gas phase based on their size, shape,
      and charge. While ion mobility spectrometry alone can be useful for some
      applications (mostly security analysis for detecting certain classes of narcotics
      and explosives), it becomes even more powerful in combination with mass
      spectrometry and high-performance liquid chromatography. Indeed, the limited
      resolving power of ion mobility spectrometry alone can be tackled when combining
      this analytical strategy with mass spectrometry or liquid chromatography with
      mass spectrometry. Over the last few years, the hyphenation of ion mobility
      spectrometry to mass spectrometry or liquid chromatography with mass spectrometry
      has attracted more and more interest, with significant progresses in both
      technical advances and pioneering applications. This review describes the
      theoretical background, available technologies, and future capabilities of these
      techniques. It also highlights a wide range of applications, from small molecules
      (natural products, metabolites, glycans, lipids) to large biomolecules (proteins,
      protein complexes, biopharmaceuticals, oligonucleotides).

PMID- 29024510
TI  - Discovery of a Potentially New Subfamily of ELFV Dehydrogenases Effective for l
      Arginine Deamination by Enzyme Mining.
AB  - Discovery of enzymes with new functions is very important for de novo pathway
      design in synthetic biology. Amino acid dehydrogenases catalyze the oxidative
      deamination of an amino acid to its keto acid, which are widely used for the
      production of various valuable chemicals. To discover amino acid dehydrogenases
      with new functions, the authors reevaluate the sequence variability and substrate
      diversity of ELFV dehydrogenases superfamily in this study. With insights gained
      from structural and sequential studies, the authors develop an in silico strategy
      and discover a new category of proteins which are originally annotated as
      glutamate dehydrogenase but show altered conservation pattern of specificity
      determined motifs and completely different substrate spectrum. These proteins
      cannot catalyze the deamination of glutamate and other canonical amino acids
      except the positively charged amino acid l-arginine, representing a potentially
      new subfamily of ELFV dehydrogenases. The strategy utilized in this study can
      also be applied for discovering other useful enzymes.

PMID- 29024511
TI  - The Relationship Between Linear Osteological and Radiographic Measurements of the
      Human Calcaneus and Talus.
AB  - Plain radiographs of the foot are a common form of examination in individuals
      when medical evaluation is indicated. Their availability makes them useful for
      studying human variation where large sample sizes are crucial. Calcaneal and
      talar morphology are critical in the understanding of human foot form and
      function, but few studies have examined the accuracy of linear measurements of
      these bones taken from radiographs. If linear measurements are to be used in
      quantitative analysis, their accuracy must first be demonstrated. For this study,
      54 human feet from amputated limbs were imaged in standard radiographic views and
      skeletonized. Selected linear measurements were made on each skeletonized talus
      and calcaneus. Corresponding landmarks were identified on the radiographic images
      and the distances between these points determined. Using the measurements taken
      from the physical bone, the accuracy of the radiographic measurements was
      evaluated employing paired Student's t-tests and correlation analysis. Most
      measurements were not significantly different (P >= 0.05). Overall, the sagittal
      plane measurements were correlated (r2 > 0.61-0.88, all P < 0.001) with the
      radiographic measurements; transverse plane measurements less so (r2 = 0.20-0.63,
      P < 0.001). These results demonstrate that measurements from radiographic images
      provide useful information concerning both the calcaneus and talus, indicating
      that radiographs of living individuals can be evaluated quantitatively and
      compared to osteology collections of modern humans. This information can be
      applied to the understanding of functional anatomy of the modern human foot,
      interpreting the hominin fossil pedal record, and establishing identification in
      forensic analysis. Anat Rec, 2017. (c) 2017 Wiley Periodicals, Inc. Anat Rec,
      301:21-33, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29024512
TI  - The clinical performance of computer-assisted liquid-based cytology, primary
      hrHPV screening, and cotesting at a Turkish Tertiary Care Hospital.
AB  - BACKGROUND: We aimed to compare the performance of computer-assisted liquid-based
      cytology, primary high-risk human papillomavirus (hrHPV) screening, and cytology
      hrHPV cotesting with regards to the detection rate of cervical cancer precursor
      lesions. METHODS: A total of 22,653 computer-assisted liquid-based cytology
      specimens interpreted between 2013 and 2015 were included in the study. We
      compared the false-negative rates and sensitivities for computer-assisted liquid
      based cytology, primary hrHPV screening and cytology-hrHPV cotesting among women
      with normal and abnormal cytologies. Among 1,748 women who had undergone
      cotesting, 249 underwent follow-up biopsies. RESULTS: For detecting biopsy
      confirmed high-grade lesions, the sensitivities of using hrHPV, Pap tests, and
      cytology-hrHPV cotesting were 90.67%, 88%, and 98.67%, respectively, while the
      false-negative rates for hrHPV and Pap tests were 9.3% and 12%, respectively. The
      false negative rate for cotesting was only 1.3%. CONCLUSION: Based on the
      significantly high sensitivity and lower false-negative rates achieved, we
      conclude that the combination of cytologic screening with hrHPV testing is the
      best preferred strategy for detection of cervical precursor lesions in our
      country's conditions.

PMID- 29024513
TI  - Fine needle aspiration of meningioma: Cytologic features on ThinPrep.

PMID- 29024514
TI  - Therapeutic potential of hAECs for early Achilles tendon defect repair through
      regeneration.
AB  - Cell-based therapy holds great promise for tendon disorders, a widespread
      debilitating musculoskeletal condition. Even if the cell line remains to be
      defined, preliminary evidences have proven that amniotic-derived cells possess in
      vitro and in vivo a great tenogenic potential. This study investigated the
      efficacy of transplanted human amniotic epithelial cells (hAECs) by testing their
      early regenerative properties and mechanisms involved on a validated ovine
      Achilles tendon partial defect performed on 29 animals. The injured tendons
      treated with hAECs recovered rapidly, in 28 days, structural and biomechanical
      properties undertaking a programmed tissue regeneration, differently from the
      spontaneous healing tissues. hAECs remained viable within the host tendons
      establishing with the endogenous progenitor cells an active dialogue. Through the
      secretion of modulatory factors, hAECs inhibited the inflammatory cells
      infiltration, activated the M2 macrophage subpopulation early recruitment, and
      accelerated blood vessel as well as extracellular matrix remodelling. In
      parallel, some in situ differentiated hAECs displayed a tenocytelike phenotype.
      Both paracrine and direct hAECs stimulatory effects were confirmed analysing
      their genome profile before and after transplantation. The 49 human up-regulated
      transcripts recorded in transplanted hAECs belonged to tendon lineage
      differentiation (epithelial-mesenchymal transition, connective specific matrix
      components, and skeleton or muscle system development-related transcripts), as
      well as the in situ activation of paracrine signalling involved in inflammatory
      and immunomodulatory response. Altogether, these evidences support the hypothesis
      that hAECs are a practicable and efficient strategy for the acute treatment of
      tendinopathy, reinforcing the idea of a concrete use of amniotic epithelial cells
      towards the clinical practice.

PMID- 29024515
TI  - Health Behavior Change in Older Adults: Testing the Health Action Process
      Approach at the Inter- and Intraindividual Level.
AB  - BACKGROUND: Health behavior change theories usually claim to be universally and
      individually applicable. Most research has tested behavior change theories at the
      interindividual level and within young-to-middle-aged populations. However,
      associations at the interindividual level can differ substantially from
      associations at the intraindividual level. This study examines the applicability
      of the Health Action Process Approach (HAPA) at the inter- and the
      intraindividual level among older adults. METHODS: Two intensive longitudinal
      studies examined the HAPA model covering two different health behaviors and two
      different time spans: Study 1 (physical activity, N = 52 * 6 monthly
      observations) and Study 2 (medication adherence, N = 64 * 30 daily observations).
      The HAPA constructs (risk awareness, outcome expectancy, self-efficacy,
      intention, action planning, action control), and self-reported behaviors were
      assessed. RESULTS: Overall, at the interindividual level, results of both studies
      largely confirmed the associations specified by the HAPA. At the intraindividual
      level, results were less in line with the HAPA. Only action control emerged as
      consistent predictor of behavior. CONCLUSIONS: This study emphasises the
      importance of examining health behavior change theories at both, the inter- and
      the intraindividual level.

PMID- 29024516
TI  - Pro: Direct-acting antivirals are associated with occurrence and recurrence of
      hepatocellular carcinoma.

PMID- 29024517
TI  - Germ Cell Migration, Proliferation and Differentiation during Gonadal
      Morphogenesis in All-Female Japanese Flounder (Paralichthys Olivaceus).
AB  - In this study, all genetic female (XX) broods of Japanese flounder were produced
      artificially by mating the females with sex-reversed males. The proliferation and
      migration of primordial germ cells (PGCs), formation of ovary and oogenesis were
      described in detail. After hatching, around 20 individual PGCs migrated from the
      lateral to the dorsal of trunk region. At 15 days posthatching (dph), a part of
      PGCs were covered by a single layer somatic cells and formed the genital ridge.
      By 22 dph, the elongated gonadal primordia appeared under the ventral kidney,
      where the PGCs were totally enclosed by somatic cells. During the process of
      migration, PGCs were presumed to be mitotically inactive. From 63 to 73 dph,
      somatic cells rearrangement resulted in the formation of a narrow crevice, which
      became deeper and formed ovarian lumen. However, at 52 dph, dramatic mitotic
      proliferation of germ cell occurred and germline nest formed before the
      appearance of ovarian lumen. The onset of intensive germ cell proliferation and
      appearance of cell nests could be accepted as a criterion of initial ovarian
      differentiation. Then germ cells and somatic epithelial cells were gradually
      delimited by basement membrane and formed the germinal epithelium. In this
      period, results from in situ hybridization revealed that the early forkhead box
      L2 (pofoxl2) was expressed in somatic cells and oocytes in primary growth, which
      indicated the prefollicle cells formed. Then oogonia or oocytes, follicle cells,
      basement membrane, and theca cells composed a follicle complex. Finally, oocytes
      underwent meiosis and developed into to mature eggs. Anat Rec, 301:727-741, 2018.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 29024518
TI  - CD5+ B lymphoproliferative disorder with subsequent development of plasma cell
      leukaemia: Diagnostic and aetiologic reasoning.
AB  - BACKGROUND: Plasma cell myeloma (PCM) has been sporadically reported to occur
      simultaneously or subsequently to mature B lymphoproliferative disorders (LPDs),
      predominantly chronic lymphocytic leukaemia (CLL). METHODS: We describe the
      clinical and laboratory findings of a 69-year-old male patient who developed
      plasma cell leukaemia (PCL) 8 years after an initial diagnosis of a low stage
      CD5+ B LPD and 3 years after treatment for LPD. RESULTS: The transition from a
      clinically indolent B LPD to an aggressive PCM was documented by bone marrow (BM)
      biopsy, while flow cytometric (FC) immunophenotyping conferred additional
      information by disclosing the co-existence of both disorders in BM and the
      presence of abnormal monotypic PCs in peripheral blood above PCL levels.
      Phenotypic findings suggested a discrete clonal origin of the two disorders.
      CONCLUSIONS: This report of PCL development in a patient with residual CD5+ B
      LPD, emphasizes the need for comprehensive diagnostic evaluation of such cases
      and scrutiny of their aetiological relationship, including FC immunophenotyping
      due to its high analytical sensitivity and multiparametric capacity compared to
      morphology or immunohistochemistry alone. (c) 2017 International Clinical
      Cytometry Society.

PMID- 29024519
TI  - Optimization of the use of a pharmaceutical grade xeno-free medium for in vitro
      expansion of human mesenchymal stem/stromal cells.
AB  - Human bone marrow-derived mesenchymal stem/stromal cells (hMSCs) are considered
      promising therapeutic agents in the field of cell therapy and regenerative
      medicine, mainly due to their relative facility to be isolated, multi
      differentiation potential, and immunomodulatory role. However, their application
      in clinics requires a crucial step of in vitro expansion. Most of the protocols
      for hMSCs in vitro culture use foetal bovine serum as medium supplement that,
      being from animal origin, presents several safety concerns and may initiate
      xenogeneic immune responses after cells transplantation. This work reports the
      optimization of a pharmaceutical-grade xeno-free strategy for hMSCs in vitro
      expansion based on the supplementation of basal medium with a pharmaceutical
      grade human plasma-derived supplement for cell culture (SCC) and 2 human growth
      factors (bFGF and TGFbeta1), plus a coating of human plasma fibronectin (Fn).
      After 4 weeks in culture, this strategy improves hMSCs expansion yield about 4.3
      fold in comparison with foetal bovine serum supplementation and 4.5-fold compared
      with a commercially available xeno-free medium. hMSCs expanded in SCC-based
      formulation maintained their phenotype and differentiation capacity into
      osteogenic, adipogenic, and chondrogenic lineages, without alterations in cell
      karyotype. Overall, the SCC-based medium appears to be an excellent alternative
      for the xeno-free expansion of hMSCs as therapeutic agents for clinical
      applications.

PMID- 29024520
TI  - Allergen immunotherapy: exploring areas for further inquiry.
AB  - BACKGROUND: Allergy-related illness impacts millions of individuals worldwide.
      Our objectives were to characterize current trends of clinical trials research
      relating to allergen immunotherapy and to describe the landscape of allergen
      immunotherapy in National Institutes of Health (NIH)-supported research inquiry.
      METHODS: On ClinicalTrials.gov, the following terms were searched: allergen
      immunotherapy OR allergy immunotherapy. Variables, including completion status,
      dates, design, study population, funder, location, and allergen were recorded.
      The NIH Research Portfolio Online Reporting Tools (RePORTER) system was also used
      to gather relevant variables. RESULTS: A total of 372 clinical trials met
      inclusion criteria. The proportion of industry-funded clinical trials has
      declined over 15 years. There has been a slow decline in pollen allergy
      immunotherapy research, with an increase in both food and animal allergy
      immunotherapy research. Otolaryngologists comprised only 6.4% of clinical trials
      principal investigators (PIs). There was a total adjusted NIH funding of
      $74,986,125 for the 118 total funding years. CONCLUSION: Despite an immense
      interest in allergen immunotherapy, this analysis demonstrates that
      otolaryngologists represented a small proportion of PIs leading associated
      clinical trials and basic science inquiry. The proportion of trials with industry
      sponsorship has declined considerably in recent decades. These trends could help
      direct future resource allocation for allergen immunotherapy.

PMID- 29024521
TI  - Role of Peroxisome Proliferator-Activated Receptor (PPARgamma) in Metabolic
      Disorders in SGA with Catch-Up Growth.
AB  - OBJECTIVE: Abnormal fat metabolism is a major disorder in adults who were small
      for gestational age (SGA). Peroxisome prolferator-activated receptor (PPARgamma)
      participates in adipocyte differentiation and the regulation of lipid metabolism.
      This study explored the role of PPARgamma in the regulation of fat catch-up
      growth (CUG) and the lipid metabolism of SGA individuals. METHODS: The CUG-SGA
      rats were treated with pioglitazone. The weight of the visceral adipose tissue,
      serum lipid levels, and PPARgamma expression in the visceral adipose tissue were
      detected at 4, 8, and 12 weeks of age. RESULTS: The PPARgamma expression in the
      visceral adipose tissue in the CUG-SGA group was lower than that in the
      appropriate for gestational age (AGA) group at 4, 8, and 12 weeks (P < 0.05). The
      serum triglycerides in the CUG-SGA group were elevated compared with that in the
      AGA group at 4 and 12 weeks (P = 0.005; P = 0.037); however, they were
      significantly decreased after 8 weeks of pioglitazone intervention (P = 0.001).
      CONCLUSIONS: PPARgamma expression in the visceral adipose tissue was lower in SGA
      rats and may be related to the regulation of adipocyte differentiation. The early
      increased PPARgamma expression by pioglitazone might reduce serum triglycerides
      and decrease the CUG of the visceral adipose tissue in SGA.

PMID- 29024523
TI  - The Royal Australian and New Zealand College of Radiologists (RANZCR), 68th
      Annual Scientific Meeting, 19-22 October 2017, Perth, Australia.

PMID- 29024522
TI  - In vitro safety evaluation of human nasal epithelial cell monolayers exposed to
      carrageenan sinus wash.
AB  - BACKGROUND: Carrageenans have shown to reduce the viral load in nasal secretions
      and lower the incidence of secondary infections in children with common cold.
      Despite the widespread use of carrageenans in topical applications, the effect of
      carrageenans on the sinonasal epithelial barrier has not been elucidated. We
      investigate the effect of different carrageenans on the sinonasal epithelial
      barrier and inflammatory response in vitro. METHODS: Iota and Kappa carrageenan
      delivered in saline irrigation solutions applied to air-liquid interface (ALI)
      cultures of primary human nasal epithelial cells from chronic rhinosinusitis
      patients and controls. Epithelial barrier structure was assessed by measuring the
      transepithelial electrical resistance (TEER) and immunolocalization of F actin.
      Ciliary beat frequency (CBF), toxicity, and inflammatory response was studied.
      RESULTS: Kappa or Iota carrageenan in the different solutions was not toxic, did
      not have detrimental effects on epithelial barrier structure and CBF. Rather,
      application of Kappa carrageenan significantly increased TEER and suppressed
      interleukin 6 (IL-6) secretion in ALI cultures from CRS patients. CONCLUSION:
      Kappa or Iota carrageenan solution was safe and did not negatively affect
      epithelial barrier function. Kappa carrageenan increased TEER and decreased IL-6
      production in CRS patients, indicating positive effects on epithelial barrier
      function in vitro.

PMID- 29024525
TI  - A novel HLA-B allele, HLA-B*35:348, was identified by sequencing-based typing.
AB  - HLA-B*35:348 has 1 nucleotide substitution, c.817G > C (GTG->CTG at codon 248)
      compared with B*35:01:01:01.

PMID- 29024526
TI  - Construction of Discrete Pentanuclear Platinum(II) Stacks with Extended Metal
      Metal Interactions by Using Phosphorescent Platinum(II) Tweezers.
AB  - Discrete pentanuclear PtII stacks were prepared by the host-guest adduct
      formation between multinuclear tweezer-type PtII complexes. The formation of the
      PtII stacks in solution was accompanied by color changes and the turning on of
      near-infrared emission resulting from Pt???Pt and pi-pi interactions. The X-ray
      crystal structure revealed the formation of a discrete 1:1 adduct, in which a
      linear stack of five PtII centers with extended Pt???Pt interactions was
      observed. Additional binding affinity and stability have been achieved through a
      multinuclear host-guest system. The binding behaviors can be fine-tuned by
      varying the spacer between the two PtII moieties in the guests. This work
      provides important insights for the construction of discrete higher-order
      supramolecular metal-ligand aggregates using a tweezer-directed approach.

PMID- 29024527
TI  - Sequence-Mandated, Distinct Assembly of Giant Molecules.
AB  - Although controlling the primary structure of synthetic polymers is itself a
      great challenge, the potential of sequence control for tailoring hierarchical
      structures remains to be exploited, especially in the creation of new and
      unconventional phases. A series of model amphiphilic chain-like giant molecules
      was designed and synthesized by interconnecting both hydrophobic and hydrophilic
      molecular nanoparticles in precisely defined sequence and composition to
      investigate their sequence-dependent phase structures. Not only compositional
      variation changed the self-assembled supramolecular phases, but also specific
      sequences induce unconventional phase formation, including Frank-Kasper phases.
      The formation mechanism was attributed to the conformational change driven by the
      collective hydrogen bonding and the sequence-mandated topology of the molecules.
      These results show that sequence control in synthetic polymers can have a
      dramatic impact on polymer properties and self-assembly.

PMID- 29024528
TI  - Photobiomodulation alters matrix protein activity in stressed fibroblast cells in
      vitro.
AB  - A balance is maintained between matrix synthesis and degradation, and a prolonged
      increase in matrix metalloproteinases (MMPs) affects healing. Photobiomodulation
      (PBM) speeds up healing and alters wound environment. The study aimed to
      determine changes in protein and gene expression of collagen type 1 (Col-I), MMP
      3 and -9 and TIMP-1 in fibroblasts irradiated at 660 or 830 nm. Commercially
      purchased human skin fibroblast cells were modeled into five groups namely,
      normal, normal wounded, diabetic wounded, hypoxic wounded and diabetic hypoxic
      wounded. Control cells were sham irradiated. Laser irradiation was conducted at
      660 or 830 nm (108/or 94 mW, 9.1 cm2 , 420/or 483 s) with 5 J/cm2 . Forty-eight
      hours post-irradiation, protein expression of TIMP-1, MMP-3, -9 and Col-I was
      determined by flow cytometry and immunofluorescence, and gene expression by real
      time RT-PCR. There was an increase in TIMP-1 and Col-I, and a decrease in MMP-3
      and -9, as well as an alteration in mRNA expression of MMP3, MMP9, TIMP1 and
      COL1A1 in irradiated cells. Due to the responsiveness of the diabetic hypoxic
      wounded model, the findings propose this model as appropriate for wound healing
      studies and suggest that PBM promotes the remodeling phase of wound healing by
      decreasing matrix degradation and upregulating synthesis.

PMID- 29024529
TI  - Catalytic, Conductive Bipolar Membrane Interfaces through Layer-by-Layer
      Deposition for the Design of Membrane-Integrated Artificial Photosynthesis
      Systems.
AB  - In the presence of an electric field, bipolar membranes (BPMs) are capable of
      initiating water disassociation (WD) within the interfacial region, which can
      make water splitting for renewable energy in the presence of a pH gradient
      possible. In addition to WD catalytic efficiency, there is also the need for
      electronic conductivity in this region for membrane-integrated artificial
      photosynthesis (AP) systems. Graphene oxide (GO) was shown to catalyze WD and to
      be controllably reduced, which resulted in electronic conductivity. Layer-by
      layer (LbL) film deposition was employed to improve GO film uniformity in the
      interfacial region to enhance WD catalysis and, through the addition of a
      conducting polymer in the process, add electronic conductivity in a hybrid film.
      Three different deposition methods were tested to optimize conducting polymer
      synthesis with the oxidant in a metastable solution and to yield the best film
      properties. It was found that an approach that included substrate dipping in a
      solution containing the expected final monomer/oxidant ratio provided the most
      predictable film growth and smoothest films (by UV/Vis spectroscopy and atomic
      force microscopy/scanning electron microscopy, respectively), whereas dipping in
      excess oxidant or co-spraying the oxidant and monomer produced heterogeneous
      films. Optimized films were found to be electronically conductive and produced a
      membrane ohmic drop that was acceptable for AP applications. Films were
      integrated into the interfacial region of BPMs and revealed superior WD
      efficiency (>=1.4 V at 10 mA cm-2 ) for thinner films (<10 bilayers~100 nm) than
      for either the pure GO catalyst or conducting polymer individually, which
      indicated that there was a synergistic effect between these materials in the
      structure configured by the LbL method.

PMID- 29024531
TI  - Identification of a novel allele, HLA-A*02:189, in a Chinese Han individual.
AB  - HLA-A*02:189 differs from HLA-A*02:01:01:01 by a single substitution in exon 3
      (846 G > T).

PMID- 29024530
TI  - FNA smears of pancreatic ductal adenocarcinoma are superior to formalin-fixed
      paraffin-embedded tissue as a source of DNA: Comparison of targeted KRAS
      amplification and genotyping in matched preresection and postresection samples.
AB  - BACKGROUND: The current study was conducted to compare DNA yield, including
      normalization to nuclear area, DNA amplification functionality, and detection of
      KRAS mutations between matched fine-needle aspiration (FNA) specimens and
      pancreatic resections diagnostic of pancreatic ductal adenocarcinoma. METHODS: A
      retrospective sample of 30 matched single FNA smears and macrodissected formalin
      fixed, paraffin-embedded (FFPE) curls (2 5-MUm curls) were compared by measuring
      the following: nuclear area (via digital image analysis), DNA yield (via NanoDrop
      spectrophotometry and Quantus fluorometry), and polymerase chain reaction
      threshold cycles for KRAS amplifications. Variants in KRAS codons 12/13 and 61
      were detected by fluorescent melt curve analyses, followed by Sanger DNA
      sequencing. RESULTS: Despite a similar nuclear area, FNA smears yielded greater
      DNA per nuclear area via 2 DNA quantification methods. KRAS codon 12 mutations
      were detected in 23 of 30 FNA specimens (77%) compared with 17 of 30 matched FFPE
      specimens (57%), for a concordance rate of 74%. No KRAS codon 13 or 61 mutations
      were detected. CONCLUSIONS: FNA specimens are a more optimal source of DNA, and
      represent an important resource in the preresection and postresection molecular
      analysis of pancreatic ductal adenocarcinoma. Cancer Cytopathol 2017;125:838-47.
      (c) 2017 American Cancer Society.

PMID- 29024532
TI  - Group IVA Element (Si, Ge, Sn)-Based Alloying/Dealloying Anodes as Negative
      Electrodes for Full-Cell Lithium-Ion Batteries.
AB  - To satisfy the increasing energy demands of portable electronics, electric
      vehicles, and miniaturized energy storage devices, improvements to lithium-ion
      batteries (LIBs) are required to provide higher energy/power densities and longer
      cycle lives. Group IVA element (Si, Ge, Sn)-based alloying/dealloying anodes are
      promising candidates for use as electrodes in next-generation LIBs owing to their
      extremely high gravimetric and volumetric capacities, low working voltages, and
      natural abundances. However, due to the violent volume changes that occur during
      lithium-ion insertion/extraction and the formation of an unstable solid
      electrolyte interface, the use of Group IVA element-based anodes in commercial
      LIBs is still a great challenge. Evaluating the electrochemical performance of an
      anode in a full-cell configuration is a key step in investigating the possible
      application of the active material in LIBs. In this regard, the recent progress
      and important approaches to overcoming and alleviating the drawbacks of Group IVA
      element-based anode materials are reviewed, such as the severe volume variations
      during cycling and the relatively brittle electrode/electrolyte interface in full
      cell LIBs. Finally, perspectives and future challenges in achieving the practical
      application of Group IVA element-based anodes in high-energy and high-power
      density LIB systems are proposed.

PMID- 29024533
TI  - Global longitudinal strain corrected by RR interval is a superior predictor of
      all-cause mortality in patients with systolic heart failure and atrial
      fibrillation.
AB  - AIMS: Quantification of systolic function in patients with atrial fibrillation
      (AF) is challenging. A novel approach, based on RR interval correction, to
      counteract the varying heart cycle lengths in AF has recently been proposed.
      Whether this method is superior in patients with systolic heart failure (HFrEF)
      with AF remains unknown. This study investigates the prognostic value of RR
      interval-corrected peak global longitudinal strain {GLSc = GLS/[RR^(1/2)]} in
      relation to all-cause mortality in HFrEF patients displaying AF during
      echocardiographic examination. METHODS AND RESULTS: Echocardiograms from 151
      patients with HFrEF and AF during examination were analysed offline. Peak global
      longitudinal strain (GLS) was averaged from 18 myocardial segments obtained from
      three apical views. GLS was indexed with the square root of the RR interval {GLSc
      = GLS/[RR^(1/2)]}. Endpoint was all-cause mortality. During a median follow-up of
      2.7 years, 40 patients (26.5%) died. Neither uncorrected GLS (P = 0.056) nor left
      ventricular ejection fraction (P = 0.053) was significantly associated with all
      cause mortality. After RR^(1/2) indexation, GLSc became a significant predictor
      of all-cause mortality (hazard ratio 1.16, 95% confidence interval 1.02-1.22, P =
      0.014, per %/s^(1/2) decrease). GLSc remained an independent predictor of
      mortality after multivariable adjustment (age, sex, mean heart rate, mean
      arterial blood pressure, left atrial volume index, and E/e') (hazard ratio 1.17,
      95% confidence interval 1.05-1.31, P = 0.005 per %/s^(1/2) decrease).
      CONCLUSIONS: Decreasing {GLSc = GLS/[RR^(1/2)]}, but not uncorrected GLS nor left
      ventricular ejection fraction, was significantly associated with increased risk
      of all-cause mortality in HFrEF patients with AF and remained an independent
      predictor after multivariable adjustment.

PMID- 29024534
TI  - Rationalizing Promiscuity Cliffs.
AB  - Compound promiscuity can be viewed in different ways. We distinguish "bad"
      promiscuity resulting from chemical liabilities, nonspecific binding, or assay
      artifacts, from "good" promiscuity representing true multitarget activities.
      Investigating multitarget activities of small molecules is scientifically
      stimulating and therapeutically relevant. To better understand the molecular
      basis of multitarget activities, structure-promiscuity relationships (SPRs) are
      explored. For this purpose, "promiscuity cliffs" (PCs) have been introduced,
      which can be rationalized as an extension of the activity cliff (AC) concept. A
      PC is defined as a pair of structural analogues that are active against different
      numbers of targets (given a difference threshold). As discussed herein PCs
      frequently capture surprising SPRs and encode many experimentally testable
      hypotheses.

PMID- 29024535
TI  - Cyto-histological correlation of Xp11.2 translocation/TFE3 gene fusion associated
      renal cell carcinoma: Report of a case with review of literature.
AB  - The MiT family translocation renal cell carcinomas (RCCs) are relatively rare in
      comparison to the conventional RCC. The cytologic features overlap with
      conventional clear cell RCC and papillary RCCs, thereby making the diagnosis
      extremely challenging. Here, we describe a case of TFE3 translocation associated
      RCC in a 58-year-old patient, with emphasis on cytomorphologic features and clues
      toward this diagnostic entity. Correlating the cytohistologic findings and review
      of touch imprints revealed that presence of hyaline nodules resembling leisegang
      rings and psammoma bodies in cytologic smears from kidney tumors serve as an
      important clue in raising a suspicion for the diagnosis of MiT family
      translocation RCCs.

PMID- 29024536
TI  - Etanercept-Induced Lymphocytic Infiltration of Jessner-Kanof.

PMID- 29024538
TI  - Retinal pulse wave velocity measurement using spectral-domain optical coherence
      tomography.
AB  - The human eyes provide a natural window for noninvasive measurement of the pulse
      wave velocity (PWV) of small arteries. By measuring the retinal PWV, the
      stiffness of small arteries can be assessed, which may better detect early
      vascular diseases. Therefore, retinal PWV measurement has attracted increasing
      attention. In this study, a jump-scanning method was proposed for noninvasive
      measurement of retinal PWV using spectral-domain optical coherence tomography (SD
      OCT). The jump-scanning method uses the phase-resolved Doppler OCT to obtain the
      pulse shapes. To realize PWV measurement, the jump-scanning method extracts the
      transit time of the pulse wave from an original OCT scanning site to another
      through a transient jump. The measured retinal arterial PWV of a young human
      subject with normal blood pressure was in the order of 20 to 30 mm/s, which was
      consistent with previous studies. As a comparison, PWV of 50 mm/s was measured
      for a young human subject with prehypertension, which was in accordance with the
      finding of strong association between retinal PWV and blood pressure. In summary,
      it is believed the proposed jump-scanning method could benefit the research and
      diagnosis of vascular diseases through the window of human eyes.

PMID- 29024539
TI  - Unprecedented Sensitivity in a Probe for Monitoring Cathepsin B:
      Chemiluminescence Microscopy Cell-Imaging of a Natively Expressed Enzyme.
AB  - Until recently, chemiluminescence cell images could only be obtained using
      luciferase-activated probes. Moreover, chemiluminescence microscopy cell-imaging
      has not been demonstrated for natively expressed enzymes like cathepsin B.
      Herein, we describe the design, synthesis, and evaluation of the first
      chemiluminescence probe for the detection and imaging of cathepsin B. The probe
      activation mechanism relies on the release of a dioxetane intermediate, which
      undergoes chemiexcitation to emit green light with high efficiency under
      physiological conditions. Using the probe, we obtained clear images of cancerous
      leukemia and colon cells. This is the first demonstration of chemiluminescence
      cell images obtained by a probe for a natively expressed endogenous enzyme. We
      anticipate that the concept presented in this study will be broadly used to
      develop analogous probes for other important proteases relevant to biomolecular
      processes.

PMID- 29024537
TI  - Association between weight gain during adjuvant chemotherapy for early-stage
      breast cancer and survival outcomes.
AB  - Obese and overweight women have an increased risk of breast cancer and worse
      outcomes at the time of diagnosis. Women tend to gain weight after breast cancer
      diagnosis and during chemotherapy for early-stage disease, which may in turn
      increase risk for worse outcomes. We examined if weight gained during adjuvant
      chemotherapy was associated with worse survival outcomes. We queried our database
      for data on patients who received adjuvant third-generation chemotherapy for
      early-stage breast cancer. Univariate and multivariate analyses by Cox regression
      were performed for survival outcomes across three categories according to BMI
      variation from start to end of chemotherapy: >0.5 kg/m2 loss or gain and stable
      BMI (+/-0.5 kg/m2 ). We included 1998 patients in this study. Women over 50 years
      old and postmenopausal were more likely to lose weight during adjuvant
      chemotherapy, whereas women under 30 years old gained more weight (P < 0.001). At
      1 year postchemotherapy, patients tended to return to their original weight (rho
      = -0.3, P < 0.001). On multivariate analysis, BMI increase of >0.5 kg/m2 compared
      to maintaining BMI was marginally associated with increased locoregional
      recurrence risk (HR: 2.53; 95% CI, 1.18-5.45; P = 0.017), adjusting for grade,
      stage, and radiation delivery. Weight variation during adjuvant chemotherapy for
      early-stage breast cancer may occur as both weight gain and weight loss in a
      balanced manner. Furthermore, this variation seems to be transient in nature and
      does not appear to significantly influence recurrence rates and overall survival.

PMID- 29024541
TI  - Development and Assessment of Fully Automated and Globally Transitive Geometric
      Morphometric Methods, With Application to a Biological Comparative Dataset With
      High Interspecific Variation.
AB  - Automated geometric morphometric methods are promising tools for shape analysis
      in comparative biology, improving researchers' abilities to quantify variation
      extensively (by permitting more specimens to be analyzed) and intensively (by
      characterizing shapes with greater fidelity). Although use of these methods has
      increased, published automated methods have some notable limitations: pairwise
      correspondences are frequently inaccurate and pairwise mappings are not globally
      consistent (i.e., they lack transitivity across the full sample). Here, we
      reassess the accuracy of published automated methods-cPDist (Boyer et al. Proc
      Nat Acad Sci 108 () 18221-18226) and auto3Dgm (Boyer et al.: Anat Rec 298 () 249
      276)-and evaluate several modifications to these methods. We show that a
      substantial percentage of alignments and pairwise maps between specimens of
      dissimilar geometries were inaccurate in the study of Boyer et al. (Proc Nat Acad
      Sci 108 () 18221-18226), despite a taxonomically partitioned variance structure
      of continuous Procrustes distances. We show these inaccuracies are remedied using
      a globally informed methodology within a collection of shapes, rather than
      relying on pairwise comparisons (c.f. Boyer et al.: Anat Rec 298 () 249-276).
      Unfortunately, while global information generally enhances maps between
      dissimilar objects, it can degrade the quality of correspondences between similar
      objects due to the accumulation of numerical error. We explore a number of
      approaches to mitigate this degradation, quantify their performance, and compare
      the generated pairwise maps (and the shape space characterized by these maps) to
      a "ground truth" obtained from landmarks manually collected by geometric
      morphometricians. Novel methods both improve the quality of the pairwise
      correspondences relative to cPDist and achieve a taxonomic distinctiveness
      comparable to auto3Dgm. Anat Rec, 301:636-658, 2018. (c) 2017 Wiley Periodicals,
      Inc.

PMID- 29024540
TI  - Infections, resistance patterns and antibiotic use in patients at a regional
      cancer centre.
AB  - BACKGROUND: Infections and antibiotic resistance patterns in patients attending
      regional Australian cancer centres are poorly described. AIMS: To document
      patient characteristics, infection types, patterns of antibiotic resistance and
      outcomes in all patients with cancer requiring inpatient management for suspected
      infection at a regional Australian cancer centre. METHODS: We studied patients
      >=18 years of age who were admitted under the oncology unit at Albury Wodonga
      Health during a 12-month period and who had a microbiological test performed for
      suspected infection during their admission. Data were extracted retrospectively
      from electronic records and analysed through descriptive statistics. RESULTS: We
      identified 275 episodes of suspected infection occurring in 208 patients (M/F:
      61%/39%). Median age was 68 years, solid tumour 76%, haematological malignancy
      24%. A positive culture was obtained in 28% of cases: Gram-positive 48.5% and
      Gram-negative 51.5%. Drug resistant Pseudomonas aeruginosa was seen in 38% (5/13)
      of pseudomonas isolates, three times the rate seen in general hospital
      admissions. Extended spectrum beta lactamase was seen in 22% of Gram-negative
      isolates. Empiric IV antibiotic choice was guideline concordant in 61% of
      neutropenic fever (NF) (NF) presentations. Only 17% of NF presentations received
      antibiotics within the recommended hour of emergency department triage. The
      inpatient mortality rate was 3%. Fifty-seven percent of NF presentations
      satisfied Multinational Association of Supportive Care in Cancer risk index
      criteria for outpatient management. CONCLUSIONS: This is the first study of this
      type in patients with cancer at an Australian regional cancer centre. The study
      highlighted key areas for improvement in antibiotic prescription and control of
      antibiotic resistance at our institution.

PMID- 29024542
TI  - The Relative Bioavailability, Food Effect, and Drug Interaction With Omeprazole
      of Momelotinib Tablet Formulation in Healthy Subjects.
AB  - Momelotinib is a potent and selective small-molecule inhibitor of JAK1/2 that is
      under investigation for the treatment of myeloproliferative neoplasms. In a phase
      1/2 study in myelofibrosis patients, once-daily dosing of a 300-mg momelotinib
      capsule was selected for further development based on a favorable benefit:risk
      profile. A tablet formulation was recently developed for further clinical
      evaluation. In this study, the relative bioavailability of the tablet formulation
      versus the initial capsule formulation and the effect of food and omeprazole on
      the pharmacokinetics of a single-dose momelotinib tablet were evaluated in
      healthy subjects. The momelotinib tablet, 200 mg, provided plasma exposure
      equivalent to the 300-mg capsule. Plasma exposure of momelotinib increased less
      than dose-proportionally from 100 to 800 mg. Food intake modestly increased Cmax
      (38% and 28% increase for low- and high-fat meals, respectively) and AUCinf (16%
      and 28% increase for low- and high-fat meals, respectively) for the momelotinib
      tablet. Omeprazole reduced the exposure of the momelotinib tablet by 36% for Cmax
      and 33% for AUCinf . Neither the food effect nor the omeprazole effect on
      momelotinib exposure was considered clinically meaningful because of the safety
      and efficacy profile of momelotinib.

PMID- 29024543
TI  - Squash cytology findings of subependymomas: A report of three cases and
      differential diagnosis.
AB  - Subependymomas are slowly growing glial tumors, corresponding to WHO grade I. Few
      descriptions of the cytologic features of this neoplasm are available. This study
      describes the cytologic features of three subependymomas, as well as their
      differential diagnosis based on cytology. Three men, aged 52, 56, and 63 years,
      presented with headache. Magnetic resonance imaging revealed a nodular
      intraventricular mass in all three patients. Intraoperative squash cytology
      specimens from the three intraventricular tumors showed nodular clusters with
      microcystic changes. Nuclei were round to oval in shape, but showed no evidence
      of severe nuclear atypia or mitoses. Histological examination showed features of
      subependymoma. Squash cytology findings, including nodular clusters, mild
      cellular atypia, microcystic changes, and mucoid material, are useful in the
      rapid intraoperative diagnosis of subependymoma.

PMID- 29024544
TI  - Squamous cell carcinoma in serous effusions: Avoiding pitfalls in this rare
      encounter.
AB  - BACKGROUND: With advent of personalized medicine, precise classification of
      malignant tumors becomes essential. Squamous cell carcinoma (SCC) is rarely found
      in serous effusions and has morphologic and immunohistochemical (IHC) overlap
      with other neoplasms. METHODS: 17-year review identified 49 fluids from 26
      patients where SCC was recognized. RESULTS: SCC was more frequent in pleural
      fluid (84%) and rare in other effusions. Lung SCC was common (65%), followed by
      head and neck (16%), with other origins less represented. 19 samples were
      diagnosed positive for SCC, 12 were reported as non-small cell carcinoma and 13
      were atypical/suspicious. Two were false negative (on hypocellular smears) and
      one was false positive (smear with small orangeophilic squamous-like cells). Two
      fluids were diagnosed as adenocarcinoma on smears and SCC on cellblocks after
      IHC. A chi-square test showed the correct diagnosis more often on cellblocks than
      smears (P-value = .0005) and all false positive, negative or misclassifications
      were done on cytology smears. Ber EP4 and MOC 31 immunostains were positive in
      most cases when performed, and the most specific immunostains for SCC were p63
      and p40. Negative mucin stains were helpful. Cytology smears are imperfect tools
      in evaluation of body fluids and SCC can be misclassified as adenocarcinoma on
      smears alone. Orangeophilic cytoplasm can lead to false positive results. The
      most useful stains for identification were p40, p63, and mucicarmine. CONCLUSION:
      The combination of clinical history with cellblock preparation and appropriate
      IHCs is the best method to ensure a correct diagnosis.

PMID- 29024545
TI  - Role of substrate biomechanics in controlling (stem) cell fate: Implications in
      regenerative medicine.
AB  - Tissue-specific stem cells reside in a specialized environment known as niche.
      The niche plays a central role in the regulation of cell behaviour and, through
      the concerted action of soluble molecules, supportive somatic cells, and
      extracellular matrix components, directs stem cells to proliferate,
      differentiate, or remain quiescent. Great efforts have been done to decompose and
      separately analyse the contribution of these cues in the in vivo environment.
      Specifically, the mechanical properties of the extracellular matrix influence
      many aspects of cell behaviour, including self-renewal and differentiation.
      Deciphering the role of biomechanics could thereby provide important insights to
      control the stem cells responses in a more effective way with the aim to promote
      their therapeutic potential. In this review, we provide a wide overview of the
      effect that the microenvironment stiffness exerts on the control of cell
      behaviour with a particular focus on the induction of stem cells differentiation.
      We also describe the process of mechanotransduction and the molecular effectors
      involved. Finally, we critically discuss the potential involvement of tissue
      biomechanics in the design of novel tissue engineering strategies.

PMID- 29024546
TI  - Editorial: Bone Reading to Predict the Future.

PMID- 29024547
TI  - Equine Endometrial Explants Undergo Significant Degenerative Changes in Culture.
AB  - This study evaluated equine endometrial explants following 12, 24, and 48 hr in
      culture. Measurement of an indicator of cell death in explant supernatant, light
      microscopy, and gene expression of biomarkers of endometrial function and
      cellular stress were used to compare the effect of six different media on explant
      viability and morphology. Viability of explants was assessed indirectly through
      measuring LDH activity in the culture supernatant. Regardless of culture medium
      composition, a significant increase in LDH activity was observed within 12 hr of
      culture, indicating occurrence of cell damage. Morphological analysis through
      light microscopy revealed degenerative changes occurring within 12 hr and, after
      48 hr, there is nearly complete loss of luminal and superficial glandular
      epithelium and diffuse detachment of deep glandular epithelium. Transcript
      abundance of prostaglandin-endoperoxide synthase 2 (PTGS2), estrogen receptor 1
      (ESR1), and vascular endothelial growth factor (VEGF) was assessed as biomarkers
      of endometrial function. A marked increase in PTGS2 and VEGF expression occurred;
      ESR1 displayed more or less steady expression levels. Above-described changes
      were seen irrespective of cell culture medium used. The marked increase in
      expression in PTGS2 expression presents a limitation to using endometrial
      explants in the current culture system to study aspects of endometrial function
      such as the inflammatory response to insemination. Anat Rec, 2017. (c) 2017 Wiley
      Periodicals, Inc. Anat Rec, 301:148-153, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29024548
TI  - Electrochemical Behavior of Pyridinium and N-Methyl Pyridinium Cations in Aqueous
      Electrolytes for CO2 Reduction.
AB  - The electrochemical reduction of aqueous pyridinium and N-methyl pyridinium ions
      is investigated in the absence and presence of CO2 and electrolysis reaction
      products on glassy carbon, Au, and Pt electrodes are studied. Unlike pyridinium,
      N-methyl pyridinium is not electroactive at the Pt electrode. The electrochemical
      reduction of the two pyridine derivatives was found to be irreversible on glassy
      carbon. These results confirmed the essential role of the N-H bond of the
      pyridinium cation. In contrast, the electrochemical response of N-methyl
      pyridinium ion at the glassy carbon electrode suggests that a specific
      interaction occurs between the glassy carbon surface and the aromatic ring of the
      pyridinium derivative. For all electrodes, an enhancement of current was observed
      in the presence of CO2 . However, NMR spectroscopy of the solutions following
      electrolysis showed no formation of methanol or other possible byproducts of the
      reduction of CO2 in the presence of either pyridinium derivative ion.

PMID- 29024549
TI  - Weight gain during incarceration: systematic review and meta-analysis.
AB  - BACKGROUND: Existing evidence suggests that the prevalence of overweight and
      obesity among prisoners in different settings is high. Evaluating weight change
      during incarceration would allow for the investigation of whether the prison
      environment indeed contributes to unfavourable weight changes. OBJECTIVES: This
      study aimed to do a systematic review and a meta-analysis of existing evidence
      regarding weight change during incarceration. METHODS AND RESULTS: We conducted a
      systematic literature search by using five different online databases and
      included grey literature. A total of 16 studies, all conducted in developed
      countries, were identified. Weight change was computed in 11 of these studies and
      was self-reported in five studies. Only two studies included youth. In all but 1
      of the 11 studies using actual assessment of weight change, there was an increase
      in body weight or body mass index on average or weight gain occurred among a
      significant proportion of participants. A meta-analysis of eight of these studies
      showed an average weight gain of 0.43 (95% CI 0.14, 0.72) lb/week. In all studies
      including perceived weight change, a high proportion (43% to 73%) of participants
      reported weight gain during incarceration. CONCLUSION: Health promotion
      activities within prisons should incorporate initiatives aimed at combating
      unhealthy weight developments.

PMID- 29024550
TI  - Biology of obesity and weight regain: Implications for clinical practice.
AB  - BACKGROUND AND PURPOSE: Weight loss is recommended as first-line therapy for many
      chronic illnesses, including obesity. Most patients who do successfully lose
      weight are unable to maintain their reduced weight. Recent research findings are
      reviewed and synthesized to explain the biology of obesity, adaptation to weight
      loss, and weight regain. FINDINGS: Weight regain is a common consequence of
      successful weight loss. Current obesity management strategies fail to take into
      consideration the underlying genetic and environmental causes of obesity.
      Available treatment modalities create a negative energy balance that stimulates
      integrated, persistent neurologic, endocrine, muscle, and adipose tissue
      adaptation to restore body weight and fat mass, independent of lifestyle changes.
      IMPLICATIONS FOR PRACTICE: Understanding the pathophysiology of obesity and
      weight loss alters nurse practitioners' responsibilities in caring for patients
      with obesity. They are responsible for expanding assessment and intervention
      strategies and offering people with obesity realistic expectations for weight
      loss and regain. They are obligated to explain weight regain when it occurs to
      minimize patient frustration. Nurse practitioners have the opportunity to adopt
      new approaches to patient advocacy, especially in the areas of public policy to
      improve diagnostic tools and adjunctive therapy for people with obesity.

PMID- 29024551
TI  - Weighing in on obesity management.

PMID- 29024552
TI  - Current pharmacotherapies for obesity: A practical perspective.
AB  - BACKGROUND AND PURPOSE: To review the currently available pharmacotherapies for
      obesity management with a particular focus on the United States. METHODS:
      Narrative review based on literature searches and the latest prescribing
      information (up to July 2017). CONCLUSIONS: Obesity pharmacotherapies may assist
      those individuals who have obesity, or overweight with comorbidities, who have
      failed to maintain weight loss with lifestyle modifications alone (caloric
      restriction and increased physical activity). Currently approved options in the
      United States include phentermine for short-term use and five obesity
      pharmacotherapies that can be used long-term (orlistat, lorcaserin, phentermine
      topiramate, naltrexone-bupropion, and liraglutide 3.0 mg). If the use of an
      obesity pharmacotherapy is indicated, treatment should be selected to provide the
      most appropriate option for each individual and their circumstances. Variables
      such as contraindications, individual comorbidities, patient choice, patient
      readiness to incorporate additional behavioral changes (e.g., alcohol
      prohibition), and cost should guide choices. IMPLICATIONS FOR PRACTICE: Each of
      the obesity pharmacotherapies has advantages and disadvantages that can help
      guide treatment choice. Those receiving treatment may also have individual
      preferences based on factors such as administration route, frequency of dosing,
      and/or safety profile. In addition, some options may be particularly appropriate
      for patients with common obesity-related complications such as depression or
      diabetes.

PMID- 29024554
TI  - Unmet needs in obesity management: From guidelines to clinic.
AB  - Despite the rather slow acceptance of obesity as a disease state, several obesity
      staging systems and weight-management guidelines have been developed and are in
      use, along with an ever-growing number of treatment options. Many primary care
      clinicians, including nurse practitioners (NPs), are at the forefront of clinical
      efforts to assist individuals with obesity, but face challenges due to lack of
      alignment and consensus among the various staging systems and guidelines. This is
      further complicated by shortfalls in clinical training related to obesity
      management and increasing complexities in reimbursement for obesity-related
      services. Unmet needs in the management of obesity thus stretch from guidelines
      to clinic. This article examines the principal barriers to effective management
      of individuals with obesity and considers how concerns might be overcome, with
      particular emphasis on the role of the NP.

PMID- 29024555
TI  - Concise Review: Tissue Engineering of Urinary Bladder; We Still Have a Long Way
      to Go?
AB  - Regenerative medicine is a new branch of medicine based on tissue engineering
      technology. This rapidly developing field of science offers revolutionary
      treatment strategy aimed at urinary bladder regeneration. Despite many promising
      announcements of experimental urinary bladder reconstruction, there has been a
      lack in commercialization of therapies based on current investigations. This is
      due to numerous obstacles that are slowly being identified and precisely
      overcome. The goal of this review is to present the current status of research on
      urinary bladder regeneration and highlight further challenges that need to be
      gradually addressed. We put an emphasis on expectations of urologists that are
      awaiting tissue engineering based solutions in clinical practice. This review
      also presents a detailed characteristic of obstacles on the road to successful
      urinary bladder regeneration from urological clinician perspective. A defined
      interdisciplinary approach might help to accelerate planning transitional
      research tissue engineering focused on urinary tracts. Stem Cells Translational
      Medicine 2017;6:2033-2043.

PMID- 29024553
TI  - Obesity: Risk factors, complications, and strategies for sustainable long-term
      weight management.
AB  - BACKGROUND AND PURPOSE: The aims of this article are to review the effects of
      obesity on health and well-being and the evidence indicating they can be
      ameliorated by weight loss, and consider weight-management strategies that may
      help patients achieve and maintain weight loss. METHODS: Narrative review based
      on literature searches of PubMed up to May 2016 with no date limits imposed.
      Search included terms such as "obesity," "overweight," "weight loss,"
      "comorbidity," "diabetes," cardiovascular," "cancer," "depression," "management,"
      and "intervention." CONCLUSIONS: Over one third of U.S. adults have obesity.
      Obesity is associated with a range of comorbidities, including diabetes,
      cardiovascular disease, obstructive sleep apnea, and cancer; however, modest
      weight loss in the 5%-10% range, and above, can significantly improve health
      related outcomes. Many individuals struggle to maintain weight loss, although
      strategies such as realistic goal-setting and increased consultation frequency
      can greatly improve the success of weight-management programs. Nurse
      practitioners have key roles in establishing weight-loss targets, providing
      motivation and support, and implementing weight-loss programs. IMPLICATIONS FOR
      PRACTICE: With their in-depth understanding of the research in the field of
      obesity and weight management, nurse practitioners are well placed to effect
      meaningful changes in weight-management strategies deployed in clinical practice.

PMID- 29024556
TI  - Synthesis of Metal Nanoparticles in Metal-Phenolic Networks: Catalytic and
      Antimicrobial Applications of Coated Textiles.
AB  - The synthesis of metal nanoparticle (NP)-coated textiles (nanotextiles) is
      achieved by a dipping process in water without toxic chemicals or complicated
      synthetic procedures. By taking advantage of the unique nature of tannic acid,
      metal-phenolic network-coated textiles serve as reducing and stabilizing sites
      for the generation of metal nanoparticles of controllable size. The textiles can
      be decorated with various metal nanoparticles, including palladium, silver, or
      gold, and exhibit properties derived from the presence of the metal
      nanoparticles, for example, catalytic activity in water (>96% over five cycles
      using palladium nanoparticles) and antibacterial activity against Gram-negative
      bacteria (inhibition of Escherichia coli using silver nanoparticles) that
      outperforms a commercial bandage. The reported strategy offers opportunities for
      the development of hybrid nanomaterials that may have application in fields
      outside of catalysis and antimicrobials, such as sensing and smart clothing.

PMID- 29024557
TI  - Body composition measurement in young children using quantitative magnetic
      resonance: a comparison with air displacement plethysmography.
AB  - BACKGROUND: Quantitative magnetic resonance (QMR) has been increasingly used to
      measure human body composition, but its use and validation in children is
      limited. OBJECTIVE: We compared body composition measurement by QMR and air
      displacement plethysmography (ADP) in preschool children from Singapore's multi
      ethnic Asian population (n = 152; mean +/- SD age: 5.0 +/- 0.1 years). METHODS:
      Agreements between QMR-based and ADP-based fat mass and fat mass index (FMI) were
      assessed using intraclass correlation coefficient (ICC), reduced major axis
      regression and Bland-Altman plot analyses. Analyses were stratified for the
      child's sex. RESULTS: Substantial agreement was observed between QMR-based and
      ADP-based fat mass (ICC: 0.85) and FMI (ICC: 0.82). Reduced major axis regression
      analysis suggested that QMR measurements were generally lower than ADP
      measurements. Bland-Altman analysis similarly revealed that QMR-based fat mass
      were (mean difference [95% limits of agreement]) -0.5 (-2.1 to +1.1) kg lower
      than ADP-based fat mass and QMR-based FMI were -0.4 (-1.8 to +0.9) kg/m2 lower
      than ADP-based FMI. Stratification by offspring sex revealed better agreement of
      QMR and ADP measurements in girls than in boys. CONCLUSIONS: QMR-based fat mass
      and FMI showed substantial agreement with, but was generally lower than, ADP
      based measures in young Asian children.

PMID- 29024559
TI  - Comparative efficacy of five long-term weight loss drugs: quantitative
      information for medication guidelines.
AB  - Quantitative information is scarce in current obesity medication guidelines, and
      they do not clearly reflect the differences in the efficacy characteristics among
      various drugs. This study quantitatively assessed the efficacy characteristics of
      five FDA-approved long-term weight loss drugs. Potentially eligible studies were
      obtained from public databases. Using the differences in the weight change from
      baseline between the drug group and the corresponding placebo group as the major
      indicator of efficacy, a time-effect model was established, and crucial
      pharmacodynamic parameters, such as the maximal efficacy, drug onset time and
      rate of body weight regain after the maximal efficacy point, were used to reflect
      the differences in efficacy among the five drugs. Finally, 50 reports (involving
      43,443 participants) were included. After deducting the placebo effects, the
      maximal efficacies (95% CI) of orlistat (120 mg), lorcaserin, naltrexone
      bupropion, phentermine-topiramate (PT, 7.5/46 mg) and liraglutide were -2.94 (
      5.82, -1.27), -3.06 (-4.39, -1.71), -6.15 (-9.78, -3.25), -7.45 (-9.76, -3.88)
      and -5.50 (-10.62, -2.97) kg at weeks 60, 54, 67, 59 and 65 respectively, and
      their rates of body weight regain were 0.51, 0.48, 0.91, 1.27and 0.43 kg per year
      respectively. The 1-year dropout rates of orlistat, lorcaserin, naltrexone
      bupropion, PT and liraglutide were 29.0, 40.9, 49.1, 34.9 and 24.3% respectively.
      In addition, a significant dose-effect correlation was observed for orlistat and
      PT. This study provides valid quantitative information for medication guidelines.

PMID- 29024558
TI  - Overweight, obesity and adiposity in survivors of childhood brain tumours: a
      systematic review and meta-analysis.
AB  - Survivors of childhood brain tumours (SCBT) have increased cardiometabolic risks,
      but the determinants of these risks are unclear. This systematic review aims to
      compare the prevalence of overweight and obesity as well as adiposity measures
      between SCBT and non-cancer controls. The PubMed, EMBASE, MEDLINE, CINAHL and the
      Cochrane Library databases were searched. The primary outcomes were the
      prevalence of overweight and obesity based on body mass index. The secondary
      outcomes were adiposity measures including percent fat mass, waist-to-hip and
      waist-to-height ratios. Forty-one studies were included in the meta-analysis. The
      prevalence of overweight and obesity combined was similar between overall SCBT,
      SCBT excluding craniopharyngioma and non-cancer controls (42.6%, 95% CI 30.1-55.1
      vs. 31.7%, 95% CI 20.4-43.0 vs. 40.4%, 95% CI 34.0-46.8). We also found that SCBT
      have higher percent fat mass (mean difference 4.1%, 95% CI 2.0-6.1), waist-to-hip
      ratio (mean difference 0.07, 95% CI 0.02-0.13) and waist-to-height ratio (mean
      difference 0.06, 95% CI 0.01-0.10) than non-cancer controls. We conclude that
      SCBT have similar overweight and obesity distribution but higher adiposity than
      non-cancer controls. More studies were needed to explore the determinants of
      adiposity and its contribution to cardiometabolic outcomes in SCBT.

PMID- 29024560
TI  - Enhanced Stem Cell Differentiation and Immunopurification of Genome Engineered
      Human Retinal Ganglion Cells.
AB  - Human pluripotent stem cells have the potential to promote biological studies and
      accelerate drug discovery efforts by making possible direct experimentation on a
      variety of human cell types of interest. However, stem cell cultures are
      generally heterogeneous and efficient differentiation and purification protocols
      are often lacking. Here, we describe the generation of clustered regularly
      interspaced short palindromic repeats(CRISPR)-Cas9 engineered reporter knock-in
      embryonic stem cell lines in which tdTomato and a unique cell-surface protein,
      THY1.2, are expressed under the control of the retinal ganglion cell (RGC)
      enriched gene BRN3B. Using these reporter cell lines, we greatly improved
      adherent stem cell differentiation to the RGC lineage by optimizing a novel
      combination of small molecules and established an anti-THY1.2-based protocol that
      allows for large-scale RGC immunopurification. RNA-sequencing confirmed the
      similarity of the stem cell-derived RGCs to their endogenous human counterparts.
      Additionally, we developed an in vitro axonal injury model suitable for studying
      signaling pathways and mechanisms of human RGC cell death and for high-throughput
      screening for neuroprotective compounds. Using this system in combination with
      RNAi-based knockdown, we show that knockdown of dual leucine kinase (DLK)
      promotes survival of human RGCs, expanding to the human system prior reports that
      DLK inhibition is neuroprotective for murine RGCs. These improvements will
      facilitate the development and use of large-scale experimental paradigms that
      require numbers of pure RGCs that were not previously obtainable. Stem Cells
      Translational Medicine 2017;6:1972-1986.

PMID- 29024561
TI  - Determination of hydroxy metabolites of cocaine in hair samples for proof of
      consumption.
AB  - Although hair is widely used to identify drug use, there is a risk of false
      positives due to environmental contamination. This especially applies to cocaine
      (COC). Several strategies such as detection of norcocaine (NCOC) or cocaethylene,
      metabolite concentration ratios or intricate washing procedures have been
      proposed to differentiate actual use from contamination. The aim of the present
      study was to identify hydroxy metabolites of COC in hair specimens, thus enabling
      unambiguous prove of ingestion. A suspect screening of 41 COC-positive samples
      for these compounds was performed by liquid chromatography-quadrupole time of
      flight-mass spectrometry (LC-QTOF-MS). Once identified, mass transitions for o-,
      p- and m-isomers of hydroxy COC as well as p- and m-isomers of hydroxy
      benzoylecgonine (BE) and hydroxy NCOC were introduced into a routine procedure
      for testing drugs of abuse in hair by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) which was applied to 576 hair samples. Hydroxy
      metabolites were present in 92.2% of COC-positive hair samples; their detection
      rate exceeded that of cocaethylene and NCOC. Moreover, p-OH-BE, m-OH-BE as well
      as p-OH-NCOC and m-OH-NCOC have been identified for the first time in COC
      positive hair specimens. Hydroxy cocainics could be detected in samples having a
      negative conclusion on drug use applying hitherto established criteria. We
      suggest a more conclusive interpretation outcome including detection of hydroxy
      metabolites into the evaluation of COC-positive hair samples.

PMID- 29024562
TI  - Health maintenance practices and healthcare experiences among international
      university students.
AB  - BACKGROUND AND PURPOSE: While over a million international students attend U.S.
      universities, there is little information to guide providers on their care.
      Differences in language and health beliefs can lead to misunderstandings and poor
      outcomes. The purpose of this study was to describe the health practices and
      healthcare experiences of international students before and after they move to
      the United States to carve out specific quality improvement activities at a
      student health center. METHODS: International students volunteered to attend
      focus groups. Data were analyzed using text coding software (Dedoose) to identify
      salient themes that reflected participants' experiences. CONCLUSIONS:
      Participants (N = 19) identified four areas of health maintenance: exercise,
      nutrition, yearly checkups, and self-care for minor ailments. While participants
      described health care in their home countries as accessible and affordable, they
      described health care in the United States as less accessible, more expensive,
      and laden with communication mishaps. IMPLICATIONS FOR PRACTICE: A broader
      educational message to international students, that is, how to maintain healthy
      habits in the United States and how to access/navigate U.S. health care, coupled
      with staff training on effective health communication and the use of interpreter
      services would enhance the health and healthcare experience of this vital
      population.

PMID- 29024563
TI  - Ligand Substituents Govern the Efficiency and Mechanistic Path of Hydrogen
      Production with [Cp*Rh] Catalysts.
AB  - We demonstrate that [Cp*Rh] complexes bearing substituted 2,2'-bipyridyl ligands
      are effective hydrogen evolution catalysts (Cp*=eta5 
      pentamethylcyclopentadienyl). Disubstitution (at the 4 and 4' positions) of the
      bipyridyl ligand (namely -tBu, -H, and -CF3 ) modulates the catalytic
      overpotential, in part due to involvement of the reduced ligand character in
      formally rhodium(I) intermediates. These reduced species are synthesized and
      isolated here; protonation results in formation of complexes bearing the unusual
      eta4 -pentamethylcyclopentadiene ligand, and the properties of these protonated
      intermediates further govern the catalytic performance. Electrochemical studies
      suggest that multiple mechanistic pathways are accessible, and that the operative
      pathway depends on the applied potential and solution conditions. Taken together,
      these results suggest synergy in metal-ligand cooperation that modulates the
      mechanisms of fuel-forming catalysis with organometallic compounds bearing
      multiple non-innocent ligands.

PMID- 29024564
TI  - Videourodynamic factors predictive of successful onabotulinumtoxinA urethral
      sphincter injection for neurogenic or non-neurogenic detrusor underactivity.
AB  - OBJECTIVE: The aim of the present study was to analyze treatment outcomes and
      identify videourodynamic factors predictive of successful urethral
      onabotulinumtoxinA treatment of neurogenic and non-neurogenic detrusor
      underactivity (DU). METHODS: Patients with DU refractory to medical treatment
      were treated with injections totaling 100 U onabotulinumtoxinA into the urethral
      sphincter. Treatment outcomes were assessed 1 month after treatment using the
      Global Response Assessment. The videourodynamic parameters evaluated included
      bladder neck status during voiding, bladder sensation, detrusor pressure, maximum
      flow rate, and post-void residual volume. Treatment outcome was analyzed by
      patient and baseline videourodynamic characteristics. RESULTS: In all, 60
      patients (27 with non-neurogenic and 33 with neurogenic DU) were included in the
      study and received urethral sphincter injections of 100 U onabotulinumtoxinA in
      total. Good outcomes were reported in 36 (60%) patients (20 [74.1%] with non
      neurogenic and 16 [48.5%] with neurogenic DU). Treatment outcome was
      significantly better in patients with non-neurogenic than neurogenic DU (P =
      .039). However, good treatment outcome was not related to age, gender, or any
      videourodynamic variables, except for an open bladder neck during voiding vs non
      opening bladder neck (94.3% vs. 12.0%; P < .0001). The duration of the
      therapeutic effect was similar between patients with non-neurogenic and
      neurogenic DU (mean [+/- SD] 7.37 +/- 3.69 vs. 7.69 +/- 3.18 months,
      respectively; P = .788). In all, 12 patients reported de novo urinary
      incontinence after urethral onabotulinumtoxinA injection, 4 of whom developed
      stress urinary incontinence and 8 who had exacerbated urgency urinary
      incontinence. CONCLUSION: Urethral sphincter injection of onabotulinumtoxinA is
      effective in 60% of patients with DU. Careful videourodynamic interpretation of
      bladder neck opening enables urologists to select appropriate candidates for
      onabotulinumtoxinA treatment.

PMID- 29024565
TI  - How to measure blood pressure in primary care offices to assure accuracy while
      maintaining efficiency.

PMID- 29024566
TI  - Carbon Textile Decorated with Pseudocapacitive VC/Vx Oy for High-Performance
      Flexible Supercapacitors.
AB  - It is demonstrated that, via V2 O5 coating by low temperature atomic layer
      deposition and subsequent pyrolysis, ubiquitous cotton textile can readily turn
      into high-surface-area carbon textile fully decorated with pseudocapacitive Vx Oy
      /VC widely usable as electrodes of high-performance supercapacitor. It is found
      that carbothermic reduction of V2 O5 (C + V2 O5 -> C' + VC + CO/CO2 (g)) leads to
      chemical/mechanical activation of carbon textile, thereby producing high-surface
      area conductive carbon textile. In addition, sequential phase transformation and
      carbide formation (V2 O5 -> Vx Oy -> VC) occurred by carbothermic reduction
      trigger decoration of the carbon textile with redox-active Vx Oy /VC. Thanks to
      the synergistic effect of electrical double layer and pseudocapacitance, the
      supercapacitors made of the hybrid carbon textile exhibit far better energy
      density (over 30-fold increase) with excellent cycling stability than the carbon
      textile simply undergone pyrolysis. The method can open up a promising and facile
      way to synthesize hybrid electrode materials for electrochemical energy storages
      possessing advantages of both electrical double layer and pseudocapacitive
      material.

PMID- 29024568
TI  - Word maturity indices with latent semantic analysis: why, when, and where is
      Procrustes rotation applied?
AB  - The aim of this paper is to describe and explain one useful computational
      methodology to model the semantic development of word representation: Word
      maturity. In particular, the methodology is based on the longitudinal word
      monitoring created by Kirylev and Landauer using latent semantic analysis for the
      representation of lexical units. The paper is divided into two parts. First, the
      steps required to model the development of the meaning of words are explained in
      detail. We describe the technical and theoretical aspects of each step. Second,
      we provide a simple example of application of this methodology with some simple
      tools that can be used by applied researchers. This paper can serve as a user
      friendly guide for researchers interested in modeling changes in the semantic
      representations of words. Some current aspects of the technique and future
      directions are also discussed. WIREs Cogn Sci 2018, 9:e1457. doi:
      10.1002/wcs.1457 This article is categorized under: Computer Science > Natural
      Language Processing Linguistics > Language Acquisition Psychology > Development
      and Aging.

PMID- 29024567
TI  - Loading-Induced Reduction in Sclerostin as a Mechanism of Subchondral Bone Plate
      Sclerosis in Mouse Knee Joints During Late-Stage Osteoarthritis.
AB  - OBJECTIVE: To establish an unbiased, 3-dimensional (3-D) approach that quantifies
      subchondral bone plate (SBP) changes in mouse joints, and to investigate the
      mechanism that mediates SBP sclerosis at a late stage of osteoarthritis (OA).
      METHODS: A new micro-computed tomography (micro-CT) protocol was developed to
      characterize the entire thickness of the SBP in the distal femur of a normal
      mouse knee. Four mouse models of severe joint OA were generated: cartilage
      specific Egfr-knockout (Egfr-CKO) mice at 2 months after surgical destabilization
      of the medial meniscus (DMM), Egfr-CKO mice with aging-related spontaneous OA,
      wild-type (WT) mice at 10 months after DMM, and WT mice at 14 weeks after DMM
      plus hemisectomy of the meniscus (DMMH) surgery. As an additional model, mice
      with knockout of the sclerostin gene (Sost-KO) were subjected to DMMH surgery.
      Knee joints were examined by micro-CT, histology, and immunohistochemical
      analyses. RESULTS: Examination of the mouse distal femur by 3-D micro-CT revealed
      a positive correlation between SBP thickness and the loading status in normal
      knees. In all 4 mouse models of late-stage OA, SBP sclerosis was restricted to
      the areas under severely eroded articular cartilage. This was accompanied by
      elevated bone formation at the bone marrow side of the SBP and a drastic
      reduction in the levels of sclerostin in osteocytes within the SBP. Unlike in WT
      mice, no further increase in the thickness of the SBP was observed in response to
      DMMH in Sost-KO mice. CONCLUSION: Since focal stress on the SBP underlying sites
      of cartilage damage increases during late stages of OA, these findings establish
      mechanical loading-induced attenuation of sclerostin expression and elevation of
      bone formation along the SBP surface as the major mechanisms characterizing
      subchondral bone phenotypes associated with severe late-stage OA in mice.

PMID- 29024569
TI  - Proline-Rich Chaperones Are Compared Computationally and Experimentally for Their
      Abilities to Facilitate Recombinant Butyrylcholinesterase Tetramerization in CHO
      Cells.
AB  - Human butyrylcholinesterase (BChE), predominantly tetramers with a residence time
      of days, offers the potential to scavenge organophosphorus pesticides and
      chemical warfare agents. Efficient assembly of human BChE into tetramers requires
      an association with proline-rich peptide chaperones. In this study, the
      incorporation of different proline-rich peptide chaperones into BChE is
      investigated computationally and experimentally. First, the authors applied
      molecular dynamic (MD) simulations to interpret the interactions between proline
      rich chaperones with human BChE tetramer domains. The P24 chaperone which
      contains 24 prolines, promoted the association of BChE tetramer with a 74%
      simulated helicity of BChE subunits, whereas the control without chaperone and
      BChE with an 8-proline chaperone (P8) complex exhibited 55.8 and 60.6% predicted
      helicity, respectively. The interaction of proline-rich chaperones with BChE
      subunits (B-P) provides a conduit to facilitate the interactions between BChE
      subunits (B-B) of the complex, which is mainly attributed to hydrophobic
      interactions and hydrogen-bond binding. Experimental assessment of these two
      proline-rich chaperones plus a 14-proline chaperone (P14) was performed and
      confirmed that P24 has superior capability to facilitate recombinant BChE (rBChE)
      tetramerization with >60% rBChE tetramer in P24-transfected rBChE cells, whereas
      P14- and P8-transfected rBChE cells had 44 and 33% rBChE tetramer, respectively.
      The rBChE control had 14% tetramer. Finally, we developed a stable rBChE tetramer
      expression system in CHO cells by enriching P24 expression in rBChE expressing
      cells. Overall, our simulations provided a design concept for identifying proline
      rich peptides that promote the rBChE tetramerization in CHO cells.

PMID- 29024571
TI  - Diffuse idiopathic skeletal hyperostosis (DISH): Increased prevalence in Pacific
      Islanders.
AB  - INTRODUCTION: Diffuse idiopathic skeletal hyperostosis (DISH) is a
      musculoskeletal disorder in which ligaments and entheses slowly become ossified,
      leading to decreased mobility and pain. The prevalence is variably reported as
      between 3% and 25% of the population over 50. In Australasia, the prevalence and
      severity of DISH has long been thought by radiologists to be high in certain
      populations, particularly among Pacific Islanders. The purpose of this study is
      to investigate the prevalence and severity of DISH in a Pacific Islander
      community. METHODS: Chest radiographs in 459 individuals were retrospectively
      reviewed to assess for the presence of features consistent with DISH, as per the
      Resnick Criteria. Each radiograph was also assessed for the number of vertebral
      bodies involved. The clinical records of these patients were accessed to obtain
      the patient's ethnicity. RESULTS: The prevalence of DISH in our group overall was
      138/459 (30%) with a prevalence of 42/96 (44%) in the Pacific Islanders. The
      difference compared to the Europeans in the group is highly significant (P <
      0.0001). CONCLUSIONS: This study verifies the high prevalence of DISH in Pacific
      Islanders.

PMID- 29024572
TI  - Radiological manifestations of immune-related adverse effects observed in
      patients with melanoma undergoing immunotherapy.
AB  - Immunotherapy drugs work by stimulating the patient's own immune system to
      recognize and destroy cancer cells. This subclass of drugs is increasingly
      administered to patients with advanced melanoma. They are also commonly
      incorporated into other cancer therapies such as non-small cell lung cancer,
      renal cancer, head and neck cancers and Hodgkin lymphoma. The most commonly
      administered immunotherapeutic agents in the treatment of melanoma include
      programmed cell death protein 1 (PD-1) inhibitors, cytotoxic T-lymphocyte antigen
      4 (CTLA-4) inhibitors and a subclass of cytokines. During treatment with these
      antibodies, a unique set of adverse effects may occur which are often called
      immune-related adverse events (irAEs). It is vital for radiologists to be aware
      of and document these side effects during routine staging or body imaging during
      therapy. Some of these include pneumonitis, colitis, hypophysitis,
      lymphadenopathy or sarcoid-like syndrome and myositis. IrAEs such as sarcoid-like
      lymphadenopathy can mimic progression of disease. Serious side effects are seen
      in less than 10% of patients, and typically emerge between 6 and 12 weeks after
      commencing treatment. The clinical manifestations of these side effects typically
      vary from mild to severe and so do the radiological findings. Patients with mild
      side effects are often treated successfully with systemic corticosteroids, while
      severe cases require cessation of immunotherapy. We provide a pictorial article
      on the common irAEs and the associated radiological manifestations.

PMID- 29024570
TI  - Deuterium-reinforced polyunsaturated fatty acids improve cognition in a mouse
      model of sporadic Alzheimer's disease.
AB  - Oxidative damage resulting from increased lipid peroxidation (LPO) is considered
      an important factor in the development of late onset/age-related Alzheimer's
      disease (AD). Deuterium-reinforced polyunsaturated fatty acids (D-PUFAs) are more
      resistant to the reactive oxygen species-initiated chain reaction of LPO than
      regular hydrogenated (H-) PUFAs. We investigated the effect of D-PUFA treatment
      on LPO and cognitive performance in aldehyde dehydrogenase 2 (Aldh2) null mice,
      an established model of oxidative stress-related cognitive impairment that
      exhibits AD-like pathologies. Mice were fed a Western-type diet containing either
      D- or H-PUFAs for 18 weeks. D-PUFA treatment markedly decreased cortex and
      hippocampus F2 -isoprostanes by approximately 55% and prostaglandin F2alpha by 20
      25% as compared to H-PUFA treatment. D-PUFAs consistently improved performance in
      cognitive/memory tests, essentially resetting performance of the D-PUFA-fed Aldh2
      /- mice to that of wild-type mice fed a typical laboratory diet. D-PUFAs
      therefore represent a promising new strategy to broadly reduce rates of LPO, and
      combat cognitive decline in AD.

PMID- 29024574
TI  - Effects of plasma jet, dielectric barrier discharge, photodynamic therapy and
      sodium hypochlorite on infected curved root canals.
AB  - The aim of this investigation was to evaluate the effects of 2 different cold
      atmospheric plasma (CAP) sources, photodynamic therapy and sodium hypochlorite
      (NaOCl), on infected root canals. Therefore, 50 standardized curved human root
      canals were infected with Enterococcus faecalis and assigned to 5 groups-negative
      control (NC), plasma jet (CAP I), dielectric barrier discharge (CAP II),
      photodynamic therapy (PDT) and NaOCl + passive ultrasonic irrigation-for 30 s.
      Colony forming units (CFUs) were determined. NaOCl was significantly more
      effective at reducing CFUs than all test groups (P < .0001 [Mann-Whitney U test])
      in both parts of the root canal. CFUs in PDT were significantly lower than those
      in CAP II (P = .015), and those in CAP I were lower than those in CAP II (P =
      .05). Among all other groups and in the apical parts, no significant differences
      were found (P > .05).

PMID- 29024573
TI  - Targeting MTA1/HIF-1alpha signaling by pterostilbene in combination with histone
      deacetylase inhibitor attenuates prostate cancer progression.
AB  - The metastasis-associated protein 1(MTA1)/histone deacetylase (HDAC) unit is a
      cancer progression-related epigenetic regulator, which is overexpressed in
      hormone-refractory and metastatic prostate cancer (PCa). In our previous studies,
      we found a significantly increased MTA1 expression in a prostate-specific Pten
      null mouse model. We also demonstrated that stilbenes, namely resveratrol and
      pterostilbene (Pter), affect MTA1/HDAC signaling, including deacetylation of
      tumor suppressors p53 and PTEN. In this study, we examined whether inhibition of
      MTA1/HDAC using combination of Pter and a clinically approved HDAC inhibitor,
      SAHA (suberoylanilide hydroxamic acid, vorinostat), which also downregulates
      MTA1, could block prostate tumor progression in vivo. We generated and utilized a
      luciferase reporter in a prostate-specific Pten-null mouse model (Pb-Cre+ ;
      Ptenf/f ; Rosa26Luc/+ ) to evaluate the anticancer efficacy of Pter/SAHA
      combinatorial approach. Our data showed that Pter sensitized tumor cells to SAHA
      treatment resulting in inhibiting tumor growth and additional decline of tumor
      progression. These effects were dependent on the reduction of MTA1-associated
      proangiogenic factors HIF-1alpha, VEGF, and IL-1beta leading to decreased
      angiogenesis. In addition, treatment of PCa cell lines in vitro with combined
      Pter and low dose SAHA resulted in more potent inhibition of MTA1/HIF-1alpha than
      by high dose SAHA alone. Our study provides preclinical evidence that Pter/SAHA
      combination treatment inhibits MTA1/HIF-1alpha tumor-promoting signaling in PCa.
      The beneficial outcome of combinatorial strategy using a natural agent and an
      approved drug for higher efficacy and less toxicity supports further development
      of MTA1-targeted therapies in PCa.

PMID- 29024576
TI  - Insight into plant cell wall chemistry and structure by combination of
      multiphoton microscopy with Raman imaging.
AB  - Spontaneous Raman scattering microspectroscopy, second harmonic generation (SHG)
      and 2-photon excited fluorescence (2PF) were used in combination to characterize
      the morphology together with the chemical composition of the cell wall in native
      plant tissues. As the data obtained with unstained sections of Sorghum bicolor
      root and leaf tissues illustrate, nonresonant as well as pre-resonant Raman
      microscopy in combination with hyperspectral analysis reveals details about the
      distribution and composition of the major cell wall constituents. Multivariate
      analysis of the Raman data allows separation of different tissue regions,
      specifically the endodermis, xylem and lumen. The orientation of cellulose
      microfibrils is obtained from polarization-resolved SHG signals. Furthermore, 2
      photon autofluorescence images can be used to image lignification. The combined
      compositional, morphological and orientational information in the proposed
      coupling of SHG, Raman imaging and 2PF presents an extension of existing
      vibrational microspectroscopic imaging and multiphoton microscopic approaches not
      only for plant tissues.

PMID- 29024577
TI  - Interpersonal barriers to recovery from borderline personality disorder: A
      qualitative analysis of patient perspectives.
AB  - Social-environmental factors have been found to be an integral part in the
      recovery process for individuals with psychiatric disabilities. There are few
      studies that have obtained patient perspectives of how their social and treatment
      environments help facilitate or impede the recovery process. The following study
      examined the self-reported interpersonal barriers to recovery among a sample of
      individuals (N = 31) with borderline personality disorder who were receiving
      dialectical behaviour therapy. The goal of study was to identify self-reported
      problematic behaviour that interferes with recovery goals and identify types of
      family, friend and/or provider behaviours that increased the likelihood of
      patients engaging in these problematic behaviours. A content analysis yielded
      three themes of problematic behaviour, and how these behaviours were reinforced
      by others, including (1) avoidance behaviours, (2) encouragement of negative
      coping and (3) communication of low behavioural expectations. Implications for
      the impact of these patterns of reinforcement within behavioural health settings
      are discussed. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 29024575
TI  - Review: Genetics and the Classification of Arthritis in Adults and Children.
AB  - Current classification of primary inflammatory arthritis begins from the
      assumption that adults and children are different. No form of juvenile idiopathic
      arthritis bears the same name as an adult arthritis, a nomenclature gap with
      implications for both clinical care and research. Recent genetic data have raised
      questions regarding this adult/pediatric divide, revealing instead broad patterns
      that span the age spectrum. Combining these genetic patterns with demographic and
      clinical data, we propose that inflammatory arthritis can be segregated into 4
      main clusters, largely irrespective of pediatric or adult onset: seropositive,
      seronegative (likely including a distinct group that usually begins in early
      childhood), spondyloarthritis, and systemic. Each of these broad clusters is
      internally heterogeneous, highlighting the need for further study to resolve
      etiologically discrete entities. Eliminating divisions based on arbitrary age
      cutoffs will enhance opportunities for collaboration between adult and pediatric
      rheumatologists, thereby helping to promote the understanding and treatment of
      arthritis.

PMID- 29024579
TI  - Impact of the Norepinephrine Prodrug Droxidopa on the QTc Interval in Healthy
      Individuals.
AB  - A double-blind, 4-period crossover study (NCT01327066) was conducted to assess
      the effect of the novel norepinephrine prodrug droxidopa on the QT interval in in
      healthy subjects. Subjects were randomized to receive a single dose of droxidopa
      600 mg (maximal dose) and 2000 mg (supratherapeutic dose) compared with the
      positive control, moxifloxacin 400 mg, and placebo, each separated by a 3-day
      washout period. Patients were monitored by continuous Holter monitoring, and
      electrocardiograms (ECGs) were extracted 0.5-23 hours after dosing. Blood samples
      for pharmacokinetic analysis were collected before dosing and after ECG data
      collection. The primary end point was the time-matched placebo-adjusted change
      from baseline in the individually corrected QT (QTcI). The time-averaged QTcI
      mean placebo-corrected changes from baseline for droxidopa 600 and 2000 mg were
      0.1 milliseconds (90%CI, -0.9 to 1.0 milliseconds) and 0.3 milliseconds (90%CI, 
      0.6 to 1.3 milliseconds), respectively, and 9 milliseconds (90%CI, 8.4-10.3
      milliseconds) for moxifloxacin. This study found no effect of either dose of
      droxidopa on cardiac repolarization using QTcI. Analysis of the
      pharmacokinetic/pharmacodynamic relationship and cardiac repolarization showed no
      association with droxidopa exposure. There were no clinically relevant effects of
      droxidopa on heart rate, atrioventricular conduction, or cardiac depolarization
      identified. No morphologic ECG changes were observed.

PMID- 29024578
TI  - Morpho-Functional Features of the Gonads of Danio rerio: the Role of Brain
      Derived Neurotrophic Factor.
AB  - Zebrafish, a suitable and widely used teleost fish model in basic biomedical
      research, displays morphophysiological features of adult gonads that share some
      commonalities with those of mammalian species. In mammals, gametogenesis is
      regulated, among several factors, by brain-derived neurotrophic factor (BDNF).
      This neurotrophin has a well-established role in the developing and adult nervous
      system, as well as gonads development and functions in vertebrate species. We
      hypothesize that BDNF has a role also in the gonadal functions of zebrafish. At
      this purpose, we investigated BDNF and its receptors p75 and TrkB in the ovary
      and testis of adult zebrafish, kept under laboratory conditions. Our results
      display (1) the expression of BDNF mRNA and pro-BDNF protein outside of the
      nervous system, specifically in the ovary and testis; (2) the presence of pro
      BDNF in primary oocytes and follicular layer, and p75 in follicular cells; (3)
      the localization of pro-BDNF in type B spermatogonia, and Sertoli cells in
      testis. Altogether, these data lead us to consider that BDNF is involved in the
      gonadal function of adult zebrafish, and mainly in the adult ovary. Anat Rec,
      2017. (c) 2017 Wiley Periodicals, Inc. Anat Rec, 301:140-147, 2018. (c) 2017
      Wiley Periodicals, Inc.

PMID- 29024580
TI  - Fos Promotes Early Stage Teno-Lineage Differentiation of Tendon Stem/Progenitor
      Cells in Tendon.
AB  - Stem cells have been widely used in tendon tissue engineering. The lack of
      refined and controlled differentiation strategy hampers the tendon repair and
      regeneration. This study aimed to find new effective differentiation factors for
      stepwise tenogenic differentiation. By microarray screening, the transcript
      factor Fos was found to be expressed in significantly higher amounts in postnatal
      Achilles tendon tissue derived from 1 day as compared with 7-days-old rats. It
      was further confirmed that expression of Fos decreased with time in postnatal rat
      Achilles tendon, which was accompanied with the decreased expression of multiply
      tendon markers. The expression of Fos also declined during regular in vitro cell
      culture, which corresponded to the loss of tendon phenotype. In a cell-sheet and
      a three-dimensional cell culture model, the expression of Fos was upregulated as
      compared with in regular cell culture, together with the recovery of tendon
      phenotype. In addition, significant higher expression of tendon markers was found
      in Fos-overexpressed tendon stem/progenitor cells (TSPCs), and Fos knock-down
      gave opposite results. In situ rat tendon repair experiments found more normal
      tendon-like tissue formed and higher tendon markers expression at 4 weeks
      postimplantation of Fos-overexpressed TSPCs derived nonscaffold engineering
      tendon (cell-sheet), as compared with the control group. This study identifies
      Fos as a new marker and functional driver in the early stage teno-lineage
      differentiation of tendon, which paves the way for effective stepwise tendon
      differentiation and future tendon regeneration. Stem Cells Translational Medicine
      2017;6:2009-2019.

PMID- 29024581
TI  - Radially Phase Segregated PtCu@PtCuNi Dendrite@Frame Nanocatalyst for the Oxygen
      Reduction Reaction.
AB  - Pt-based alloy nanoframes have shown great potential as electrocatalysts toward
      the oxygen reduction reaction (ORR) in fuel cells. However, the intrinsically
      infirm nanoframes could be severely deformed during extended electro-cyclings,
      which eventually leads to the loss of the initial catalytic activity. Therefore,
      the structurally robust nanoframe is a worthy synthetic target. Furthermore,
      ternary alloy phase electrocatalysts offer more opportunities in optimizing the
      stability and activity than binary alloy ones. Herein, we report a robust PtCuNi
      ternary nanoframe, structurally fortified with an inner-lying PtCu dendrite,
      which shows a highly active and stable catalytic performance toward ORR.
      Remarkably, the PtCu@PtCuNi catalyst exhibited 11 and 16 times higher mass and
      specific activities than those of commercial Pt/C.

PMID- 29024582
TI  - Photocontrol of the Hv1 Proton Channel.
AB  - The voltage-gated proton channel Hv1 is expressed in various human cell types,
      including macrophages, epithelial cells, and sperm. Hv1 opening leads to proton
      efflux that alkalizes the cytosol. Here, we describe light-activated Hv1
      inhibitors (photoswitches) that allow controlling its activity with high
      spatiotemporal precision. The photoswitches comprise a light-sensitive azobenzene
      moiety and 2-guanidinobenzimidazole (2GBI), a known Hv1 inhibitor. In the dark,
      photoGBI inhibits heterologously expressed Hv1 channels. Blue light, which
      isomerizes the azobenzene group from trans to cis conformation, releases
      inhibition. We demonstrate photocontrol of native proton currents in human
      macrophages and sperm using photoGBI, underlining their use as valuable
      optochemical tools to study the function of Hv1 channels.

PMID- 29024583
TI  - Endowing Hydrochromism to Fluorans via Bioinspired Alteration of Molecular
      Structures and Microenvironments and Expanding Their Potential for Rewritable
      Paper.
AB  - Interest and effort toward new materials for rewritable paper have increased
      dramatically because of the exciting advantages for sustainable development and
      better nature life cycle. Inspired by how nature works within living systems,
      herein, we have used fluorans, as a concept verification, to endow original
      acidochromic, basochromic or photochromic molecules with broader properties, such
      as switchable with solvent, water, heat, electricity, stress, other force, etc.,
      via simplified methods (i.e., via variation of submolecular structure or
      microenvironments). The hydrochromic visual change and reversible behavior of
      selected molecules have been explored, and the primary mechanism at the atomic or
      subatomic level has been hypothesized. In addition, several newly demonstrated
      hydrochromic fluorans have been utilized for water-jet rewritable paper (WJRP),
      which exhibit great photostability, high hydrochromic contrast, and fast
      responsive rate and which can be reused at least 30 times without significant
      variation. The water-jet prints have good resolution and various colors and can
      keep legibility after a few months or years. This improved performance is a major
      step toward practical applications of WJRP.

PMID- 29024584
TI  - Computational Prediction of Rate Constants for Reactions Involved in Al
      Clustering.
AB  - Aluminum (Al) clustering processes via three types of association reactions are
      herein studied using classical molecular dynamics trajectory calculations. The
      simulations were carried out under realistic experimental conditions. The
      dependence of rate constants on temperature and cluster size was obtained. The
      association reactions have a very small activation barrier, and the activation
      energy increases with increasing temperature. Our prediction of reaction rate
      constants can be of interest for the study of Al nanoparticle growth using
      kinetic models.

PMID- 29024585
TI  - N,S,P Co-Doped Carbon Nanodot Fabricated from Waste Microorganism and Its
      Application for Label-Free Recognition of Manganese(VII) and l-Ascorbic Acid and
      AND Logic Gate Operation.
AB  - A novel fluorescent probe based on N,S,P codoped carbon nanodots (N,S,P-CNDSac)
      is very simple and quickly fabricated by a one-step hydrothermal pyrolysis of
      Saccharomyces cerevisiae and utilized for label-free and "on-off-on" sequential
      detection of manganese(VII) and l-ascorbic acid (l-AA). The fluorescence of N,S,P
      CNDSac can be effectively quenched by Mn(VII) based on an inner filter effect
      (IFE) and recovered upon the addition of l-AA due to the easy conversion of
      Mn(VII) to reduced states (i.e., Mn(IV), Mn(II), and Mn(0)) by l-AA. This probe
      exhibited favorable selectivity and sensitivity toward Mn(VII) and l-AA with
      detection limits of 50 nmol/L and 1.2 MUmol/L, respectively. Simultaneously, an
      "AND" logic gate based on the as-fabricated N,S,P-CNDSac has been constructed.
      Also, the as-proposed fluorescent probe was extended to detect Mn(VII) and l-AA
      in biosystems. Furthermore, the as-constructed fluorescent probe system was
      successfully applied to the analyses of Mn(VII) in tap water, Fenhe River water,
      and medicinal herb samples with satisfactory results. The proposed method is
      simple and easily accessible, demonstrating the great potential of N,S,P-CNDSac
      in biosensing, disease diagnosis, cellular labeling, and environmental
      monitoring.

PMID- 29024586
TI  - How Many Conformations Need To Be Sampled To Obtain Converged QM/MM Energies? The
      Curse of Exponential Averaging.
AB  - Combined quantum mechanical and molecular mechanical (QM/MM) calculations is a
      popular approach to study enzymatic reactions. They are often based on a set of
      minimized structures obtained on snapshots from a molecular dynamics simulation
      to include some dynamics of the enzyme. It has been much discussed how the
      individual energies should be combined to obtain a final estimate of the energy,
      but the current consensus seems to be to use an exponential average. Then, the
      question is how many snapshots are needed to reach a reliable estimate of the
      energy. In this paper, I show that the question can be easily be answered if it
      is assumed that the energies follow a Gaussian distribution. Then, the outcome
      can be simulated based on a single parameter, sigma, the standard deviation of
      the QM/MM energies from the various snapshots, and the number of required
      snapshots can be estimated once the desired accuracy and confidence of the result
      has been specified. Results for various parameters are presented, and it is shown
      that many more snapshots are required than is normally assumed. The number can be
      reduced by employing a cumulant approximation to second order. It is shown that
      most convergence criteria work poorly, owing to the very bad conditioning of the
      exponential average when sigma is large (more than ~7 kJ/mol), because the
      energies that contribute most to the exponential average have a very low
      probability. On the other hand, sigma serves as an excellent convergence
      criterion.

PMID- 29024587
TI  - Discovery of a Distinct Chemical and Mechanistic Class of Allosteric HIV-1
      Integrase Inhibitors with Antiretroviral Activity.
AB  - Allosteric integrase inhibitors (ALLINIs) bind to the lens epithelial-derived
      growth factor (LEDGF) pocket on HIV-1 integrase (IN) and possess potent antiviral
      effects. Rather than blocking proviral integration, ALLINIs trigger IN
      conformational changes that have catastrophic effects on viral maturation,
      rendering the virions assembled in the presence of ALLINIs noninfectious. A high
      throughput screen for compounds that disrupt the IN.LEDGF interaction was
      executed, and extensive triage led to the identification of a t-butylsulfonamide
      series, as exemplified by 1. The chemical, biochemical, and virological
      characterization of this series revealed that 1 and its analogs produce an ALLINI
      like phenotype through engagement of IN sites distinct from the LEDGF pocket. Key
      to demonstrating target engagement and differentiating this new series from the
      existing ALLINIs was the development of a fluorescence polarization probe of IN
      (FLIPPIN) based on the t-butylsulfonamide series. These findings further solidify
      the late antiviral mechanism of ALLINIs and point toward opportunities to develop
      structurally and mechanistically novel antiretroviral agents with unique
      resistance patterns.

PMID- 29024588
TI  - Uptake, Accumulation, and in Planta Distribution of Coexisting Cerium Oxide
      Nanoparticles and Cadmium in Glycine max (L.) Merr. .
AB  - Agricultural soils are likely to be polluted by both conventional and emerging
      contaminants at the same time. Understanding the interactions of coexisting
      engineered nanoparticles (ENPs) and trace elements (a common source of abiotic
      stress) is critical to gaining insights into the accumulation of these two groups
      of chemicals by plants. The objectives of this study were to determine the uptake
      and accumulation of coexisting ENPs and trace elements by soybeans and to gain
      insights into the physiological mechanisms resulting in different plant
      accumulation of these materials. The combinations of three cadmium levels (0
      [control] and 0.25 and 1 milligrams per kilogram of dry soil) and two CeO2 NPs
      concentrations (0 [control] and 500 milligrams per kilogram of dry soil) were
      investigated. Measurements of the plant biomass and physiological parameters
      indicated that CeO2 NPs led to higher variable fluorescence to maximum
      fluorescence ratio, suggesting that CeO2 NPs enhanced the plant light energy use
      efficiency by photosystem II. In addition, the presence of CeO2 NPs did not
      affect Cd accumulation in soybean, but Cd significantly increased the
      accumulation of Ce in plant tissues, especially in roots and older leaves. The
      altered Ce in planta distribution was partially associated with the formation of
      root apoplastic barriers in the co-presence of Cd and CeO2 NPs.

PMID- 29024589
TI  - Knocking Out OsPT4 Gene Decreases Arsenate Uptake by Rice Plants and Inorganic
      Arsenic Accumulation in Rice Grains.
AB  - Arsenic (As) accumulation in rice grains poses health risk to humans. Plants
      including rice take up arsenate (AsV) by phosphate transporters. In this study,
      rice phosphate transporter OsPT4 (OsPht1;4) was investigated based on two
      independent T-DNA insertion mutants of OsPT4 (M1 and M2), which displayed
      stronger AsV resistance than wild types WT1 and WT2. When cultivated in medium
      (+P or -P) with AsV, ospt4 mutants accumulated 16-32% lower As in plants,
      suggesting that OsPT4 mediates AsV uptake. Analysis of the xylem sap showed that
      AsV concentrations in ospt4 mutants was 20-40% lower than WT controls under -P
      condition, indicating OsPT4 may also mediate AsV translocation. Moreover,
      kinetics analysis showed that ospt4 mutants had lower AsV uptake rates than the
      WT controls, further proving that OsPT4 functions as an AsV transporter in rice.
      When grown in flooded soils with As, AsV concentrations in rice grains of ospt4
      mutants decreased by 50-55%. More importantly, knocking out OsPT4 in M1 and M2
      reduced inorganic As accumulation in rice grains by 20-44%, significant for
      controlling As exposure risk from rice. Taken together, our findings revealed a
      critical role of OsPT4 in AsV uptake and translocation in rice. Knocking out
      OsPT4 effectively decreased inorganic As accumulation in rice grains, shedding
      light on engineering low-As rice to enhance food safety.

PMID- 29024592
TI  - Hard Single-Molecule Magnet Behavior by a Linear Trinuclear Lanthanide
      [1]Metallocenophane Complex.
AB  - A synthetic protocol was developed that involves the transmetalation of a mono
      dysprosium-[1]ferrocenophane complex with DyX3 (X = Cl- or I-) to afford
      [Dy3Fc6Li2(THF)2]-, featuring a rare linear arrangement of magnetically
      anisotropic Dy3+ ions. The close spatial inter-lanthanide proximity, in
      combination with MU2-bridging sp2-hybridized CCp groups, enforces significant
      magnetic coupling and results in hard single-molecule magnet (SMM) behavior, with
      an effective barrier to magnetization reversal of up to 268 cm-1. Our results
      highlight the versatility of lanthanide metallocenophane architectures toward the
      development of novel multinuclear SMM frameworks.

PMID- 29024590
TI  - Efficient Synthesis of 1,9-Substituted Benzo[h][1,6]naphthyridin-2(1H)-ones and
      Evaluation of their Plasmodium falciparum Gametocytocidal Activities.
AB  - A novel three-component, two-step, one-pot nucleophilic aromatic substitution
      (SNAr)-intramolecular cyclization-Suzuki coupling reaction was developed for the
      synthesis of benzo[h][1,6]naphthyridin-2(1H)-ones (Torins). On the basis of the
      new efficiently convergent synthetic route, a library of Torin analogs was
      synthesized. The antimalarial activities of these compounds were evaluated
      against asexual parasites using a growth inhibition assay and gametocytes using a
      viability assay.

PMID- 29024593
TI  - Strongly Correlated Rafts in Both Leaves of an Asymmetric Bilayer.
AB  - I consider a model of a bilayer characterized by two order parameters, one in
      each leaf. That of the inner leaf represents the difference in mole fractions of
      lipids with large spontaneous curvature, phosphatidylethanolamine (PE), and those
      with small spontaneous curvatures, phosphatidylcholine (PC) and
      phosphatidylserine (PS). Similarly, the order parameter in the outer leaf
      represents the difference in mole fractions of lipids with small spontaneous
      curvature, PC, and large curvature, sphingomyelin (SM). Each order parameter is
      coupled to the variations in the height of the membrane that is assumed to be of
      constant thickness. The couplings are of different strength. I show that, with
      reasonable parameters, a microemulsion is formed in each leaf, and that the two
      microemulsions are strongly coupled. Their characteristic size of domains is
      found to be on the order of 75 nm. In this picture, rafts consist of regions of
      SM in the outer leaf and PC and PS in the inner leaf, floating in a sea of PC in
      the outer leaf and PE in the inner leaf. I argue that microemulsions have been
      observed, but not identified as such, in model systems.

PMID- 29024591
TI  - Small-Molecule Inhibitors of the CD40-CD40L Costimulatory Protein-Protein
      Interaction.
AB  - Costimulatory interactions are required for T cell activation and development of
      an effective immune response; hence, they are valuable therapeutic targets for
      immunomodulation. However, they, as all other protein-protein interactions, are
      difficult to target by small molecules. Here, we report the identification of
      novel small-molecule inhibitors of the CD40-CD40L interaction designed starting
      from the chemical space of organic dyes. For the most promising compounds such as
      DRI-C21045, activity (IC50) in the low micromolar range has been confirmed in
      cell assays including inhibition of CD40L-induced activation in NF-kappaB sensor
      cells, THP-1 myeloid cells, and primary human B cells as well as in murine
      allogeneic skin transplant and alloantigen-induced T cell expansion in draining
      lymph node experiments. Specificity versus other TNF-superfamily interactions
      (TNF-R1-TNF-alpha) and lack of cytotoxicity have also been confirmed at these
      concentrations. These novel compounds provide proof-of-principle evidence for the
      possibility of small-molecule inhibition of costimulatory protein-protein
      interactions, establish the structural requirements needed for efficient CD40
      CD40L inhibition, and serve to guide the search for such immune therapeutics.

PMID- 29024594
TI  - Stability of Schottky and Ohmic Au Nanocatalysts to ZnO Nanowires.
AB  - Manufacturable nanodevices must now be the predominant goal of nanotechnological
      research to ensure the enhanced properties of nanomaterials can be fully
      exploited and fulfill the promise that fundamental science has exposed. Here, we
      test the electrical stability of Au nanocatalyst-ZnO nanowire contacts to
      determine the limits of the electrical transport properties and the metal
      semiconductor interfaces. While the transport properties of as-grown Au
      nanocatalyst contacts to ZnO nanowires have been well-defined, the stability of
      the interfaces over lengthy time periods and the electrical limits of the ohmic
      or Schottky function have not been studied. In this work, we use a recently
      developed iterative analytical process that directly correlates multiprobe
      transport measurements with subsequent aberration-corrected scanning transmission
      electron microscopy to study the electrical, structural, and chemical properties
      when the nanowires are pushed to their electrical limits and show structural
      changes occur at the metal-nanowire interface or at the nanowire midshaft. The
      ohmic contacts exhibit enhanced quantum-mechanical edge-tunneling transport
      behavior because of additional native semiconductor material at the contact edge
      due to a strong metal-support interaction. The low-resistance nature of the ohmic
      contacts leads to catastrophic breakdown at the middle of the nanowire span where
      the maximum heating effect occurs. Schottky-type Au-nanowire contacts are
      observed when the nanowires are in the as-grown pristine state and display
      entirely different breakdown characteristics. The higher-resistance rectifying I
      V behavior degrades as the current is increased which leads to a permanent
      weakening of the rectifying effect and atomic-scale structural changes at the
      edge of the Au interface where the tunneling current is concentrated.
      Furthermore, to study modified nanowires such as might be used in devices the
      nanoscale tunneling path at the interface edge of the ohmic nanowire contacts is
      removed with a simple etch treatment and the nanowires show similar I-V
      characteristics during breakdown as the Schottky pristine contacts. Breakdown is
      shown to occur either at the nanowire midshaft or at the Au contact depending on
      the initial conductivity of the Au contact interface. These results demonstrate
      the Au-nanowire structures are capable of withstanding long periods of electrical
      stress and are stable at high current densities ensuring they are ideal
      components for nanowire-device designs while providing the flexibility of
      choosing the electrical transport properties which other Au-nanowire systems
      cannot presently deliver.

PMID- 29024595
TI  - Organelle-Specific Triggered Release of Immunostimulatory Oligonucleotides from
      Intrinsically Coordinated DNA-Metal-Organic Frameworks with Soluble Exoskeleton.
AB  - DNA has proven of high utility to modulate the surface functionality of metal
      organic frameworks (MOFs) for various biomedical applications. Nevertheless,
      current methods for preparing DNA-MOF nanoparticles rely on either inefficient
      covalent conjugation or specific modification of oligonucleotides. In this work,
      we report that unmodified oligonucleotides can be loaded on MOFs with high
      density (~2500 strands/particle) via intrinsic, multivalent coordination between
      DNA backbone phosphate and unsaturated zirconium sites on MOFs. More
      significantly, surface-bound DNA can be efficiently released in either bulk
      solution or specific organelles in live cells when free phosphate ions are
      present. As a proof-of-concept for using this novel type of DNA-MOFs in
      immunotherapy, we prepared a construct of immunostimulatory DNA-MOFs (isMOFs) by
      intrinsically coordinating cytosine-phosphate-guanosine (CpG) oligonucleotides on
      biocompatible zirconium MOF nanoparticles, which was further armed by a
      protection shell of calcium phosphate (CaP) exoskeleton. We demonstrated that
      isMOFs exhibited high cellular uptake, organelle specificity, and spatiotemporal
      control of Toll-like receptors (TLR)-triggered immune responses. When isMOF
      reached endolysosomes via microtubule-mediated trafficking, the CaP exoskeleton
      dissolved in the acidic environment and in situ generated free phosphate ions. As
      a result, CpG was released from isMOFs and stimulated potent immunostimulation in
      living macrophage cells. Compared with naked CpG-MOF, isMOFs exhibited 83-fold up
      regulation in stimulated secretion of cytokines. We thus expect this isMOF design
      with soluble CaP exoskeleton and an embedded sequential "protect-release" program
      provides a highly generic approach for intracellular delivery of therapeutic
      nucleic acids.

PMID- 29024596
TI  - Wavelength Dependence of Light-Induced Cycloadditions.
AB  - The wavelength-dependent conversion of two rapid photoinduced ligation reactions,
      i.e., the light activation of o-methylbenzaldehydes, leading to the formation of
      reactive o-quinodimethanes (photoenols), and the photolysis of 2,5
      diphenyltetrazoles, affording highly reactive nitrile imines, is probed via a
      monochromatic wavelength scan at constant photon count. The transient species are
      trapped by cycloaddition with N-ethylmaleimide, and the reactions are traced by
      high resolution mass spectrometry and nuclear magnetic resonance spectroscopy.
      The resulting action plots are assessed in the context of Beer-Lambert's law and
      provide combined with time-dependent density functional theory and multireference
      calculations an in-depth understanding of the underpinning mechanistic processes,
      including conical intersections. The pi -> pi* transition of the carbonyl group
      of the o-methylbenzaldehyde correlates with a highly efficient conversion to the
      cycloadduct, showing no significant wavelength dependence, while conversion
      following the n -> pi* transition proceeds markedly less efficient at longer
      wavelengths. The influence of absorbance and reactivity has critical consequences
      for an effective reaction design: At high concentrations of o-methylbenzaldehydes
      (c = 8 mmol L-1), photoligations with N-ethylmaleimide (possible for lambda <=
      390 nm) are ideally performed at 330 nm, whereas at high light penetration
      regimes at lower concentrations (c = 0.3 mmol L-1), 315 nm irradiation leads to
      the highest conversion. Activation and trapping of 2,5-diphenyltetrazoles
      (possible for lambda <= 322 nm) proceeds best at a wavelength shorter than 295
      nm, irrespective of concentration.

PMID- 29024597
TI  - Significant Chondrocyte Viability Is Present in Acetabular Chondral Flaps
      Associated With Femoroacetabular Impingement.
AB  - BACKGROUND: Patients presenting with cam deformity of the femoral head and neck
      sustain repeated trauma to the articular cartilage of the superior acetabulum,
      with chondral delamination injuries found during hip arthroscopy. Two previous
      studies reveal conflicting chondrocyte viability data in these traumatic
      cartilage injuries. The full-thickness nature of flaps may suggest that
      chondrocytes residing in the cartilage flap matrix in the joint environment would
      remain viable despite shear trauma. Hypothesis/Purpose: The purpose of this study
      is to determine the in vivo tissue viability of acetabular chondral flaps in
      patients with femoroacetabular impingement (FAI) when samples are analyzed
      immediately after biopsy. We hypothesize that the majority of the tissue in
      acetabular chondral flaps is viable in the joint microenvironment. STUDY DESIGN:
      Descriptive laboratory study. METHODS: Partially detached cartilage flaps from 10
      patients undergoing arthroscopic hip surgery for FAI were biopsied in a minimally
      traumatic manner before chondroplasty and microfracture. Samples were placed in
      cold Hank's Balanced Salt Solution without phenol red solution and immediately
      transported on ice to our laboratory. The edge of the samples was trimmed and
      further cut into 3 separate, 1-mm-thick sections. Sections were stained using a
      live/dead staining kit. Images were obtained with confocal microscopy, and the
      percentage of live cells was quantified. RESULTS: Patients averaged 36 +/- 11
      years (range, 18-48 years), and 2 patients were female. The mean body mass index
      was 28.9 +/- 5.6 kg/m2. The total proportion of live cells from all sections
      analyzed was 85.8%. The proportion of live cells per patient was 87% +/- 10%.
      CONCLUSION: We determined that acetabular chondral flaps are approximately 87%
      live cells when analyzed immediately after biopsy, with 6 of 10 patients having
      greater than 90% live cells. These data point to the importance of laboratory
      techniques in making viability judgments in biologic systems. CLINICAL RELEVANCE:
      Full-thickness cartilage loss is a difficult problem for all active people but
      particularly in the young population in whom joint preservation is key. We
      describe the viability of chondrocytes present in full-thickness acetabular-based
      chondral flaps encountered during hip arthroscopy. Identification of greater than
      85% chondrocyte viability supports a foundation for evaluation and creation of
      novel clinical innovations for repair and replacement techniques using the flap
      as donor tissue, as alternatives to chondroplasty and microfracture.

PMID- 29024599
TI  - The effects of combined probiotic ingestion and circuit training on muscular
      strength and power and cytokine responses in young males.
AB  - To our knowledge, the efficacy of combined probiotic supplementation with circuit
      training has not been evaluated. Thus, we investigated the effects of probiotic
      supplementation combined with circuit training on isokinetic muscular strength
      and power and cytokine responses in young males. Forty-eight healthy sedentary
      young males were recruited and randomised into 4 separate groups: sedentary
      placebo control, probiotics (P), circuit training with placebo (CT), and circuit
      training with probiotics (CTP). Participants in the CT and CTP groups performed
      circuit training 3 times/week with 2 circuits of exercises from weeks 1-8
      followed by 3 circuits of exercises from weeks 9-12. Participants in the P and
      CTP groups consumed multi-strain probiotics containing 3 * 1010 colony-forming
      units of Lactobacillus acidophilus, L. lactis, L. casei, Bifidobacterium longum,
      B. bifidum and B. infantis twice daily for 12 weeks. Measurements of body height
      and weight, blood pressure, resting heart rate, blood samples, and isokinetic
      muscular strength and power were carried out at pre- and post-tests. Isokinetic
      knee strength and power in CT and CTP groups were significantly higher (P < 0.05)
      at post-test. In addition, interleukin (IL)-10 concentration was significantly
      increased (P < 0.0001) at post-test in P and CT but a trend toward significant
      increase in CTP (P = 0.09). Nevertheless, there was no significant difference in
      IL-6. This study suggests that 12 weeks of circuit training alone and the
      combination of circuit training and probiotic consumption improved muscular
      performance while circuit training alone and probiotics alone increased IL-10
      concentration.

PMID- 29024598
TI  - Effects of long-term exposures to low iron and branched-chain amino acid
      containing diets on aging skeletal muscle of Fisher 344 * Brown Norway rats.
AB  - Aging skeletal muscle displays an altered iron status that may promote oxidative
      stress and sarcopenia. A diet containing low iron (LI) could reduce muscle iron
      status and attenuate age-related muscle atrophy. Supplemental branched-chain
      amino acids (BCAA) may also alleviate sarcopenia by promoting muscle protein
      synthesis and iron status improvement. This study examined individual and
      combined effects of LI and BCAA diets on anabolic signaling and iron status in
      skeletal muscle of aging rats. Twenty-nine-month-old male Fisher 344 * Brown
      Norway rats consumed the following control-base diets: control + regular iron (35
      mg iron/kg) (CR; n = 11); control + LI (~6 mg iron/kg) (CL; n = 11); 2*BCAA +
      regular iron (BR; n = 10); and 2*BCAA + LI (BL; n = 12) for 12 weeks. Although LI
      and/or 2*BCAA did not affect plantaris muscle mass, 2*BCAA groups showed lower
      muscle iron content than did CR and CL groups (P < 0.05). p70 ribosomal protein
      S6 kinase phosphorylation was greater in 2*BCAA and LI animals compared with CR
      animals (P < 0.05). Interactions between IRON and BCAA were observed for proteins
      indicative of mitochondrial biogenesis (peroxisome proliferator-activated
      receptor gamma coactivator 1 alpha) and oxidative capacity (cytochrome c oxidase
      subunit 2 and citrate synthase) (P < 0.05) wherein the combined diet (BL) negated
      potential benefits of individual diets. Antioxidant capacity, superoxide
      dismutase activity, and oxidative injury (3-nitrotyrosine, protein carbonyls, and
      4-hydroxynonenal) were similar between groups. In conclusion, 12 weeks of LI and
      2*BCAA diets showed significant impacts on increasing anabolic signaling as well
      as ameliorating iron status; however, these interventions did not affect muscle
      mass.

PMID- 29024600
TI  - Liver X receptor alpha is targeted by microRNA-1 to inhibit cardiomyocyte
      apoptosis through a ROS-mediated mitochondrial pathway.
AB  - Diabetic cardiomyopathy (DCM) is defined as ventricular dysfunction occurring
      independently of a recognized cause such as hypertension or coronary artery
      disease. Liver X receptor alpha (LXRalpha), a subtype of ligand-activated
      transcription factors LXRs, has been considered as a potential pharmacological
      target in the pathogenesis of cardiovascular and metabolic diseases. However, the
      potential mechanism of how LXRalpha is regulated in cardiomyocytes is still
      unclear. This study investigated the effect of activating LXRalpha with GW3965 on
      cardiomyocyte apoptosis and its upstream regulator in glucose-induced H9C2 cells.
      Our data indicated that GW3965 up-regulated the expression of LXRalpha, inhibited
      cardiomyocyte apoptosis, and altered the apoptosis-related proteins in glucose
      induced H9C2 cells. In addition, GW3965 restored the mitochondrial membrane
      potential level and decreased the ROS production induced by glucose. Moreover,
      LXRalpha was confirmed as a direct target of microRNA-1 (miR-1) that was involved
      in cardiomyocyte apoptosis of DCM, and overexpression of miR-1 abrogated the
      inhibiting effect of GW3965 on glucose-induced apoptosis in H9C2 cells. This
      study highlights an important role of LXRalpha in the development of DCM and
      brings new insights into the complex mechanisms involved in the pathogenesis of
      DCM.

PMID- 29024601
TI  - A Biomechanical Analysis of the Association Between Forearm Mechanics and the
      Elbow Varus Moment in Collegiate Baseball Pitchers.
AB  - BACKGROUND: The incidence of upper extremity injury in baseball pitchers has
      increased over the past decade. This has resulted in a large body of research
      mainly focused on the kinematic and kinetic patterns of the elbow and shoulder to
      elucidate the cause of these injuries, with little attention on studying the
      associations of forearm rotation and upper arm joint moments. HYPOTHESIS: There
      will be significant differences in forearm kinematics and kinetics when comparing
      the fastball pitch with the curveball pitch. There will be a positive association
      between forearm kinetics, specifically supination and pronation moments, and the
      elbow varus moment. STUDY DESIGN: Descriptive laboratory study. METHODS: A total
      of 78 pitchers were recruited for this study, and they underwent a pitching
      analysis using motion analysis techniques. A random-intercept, mixed-effects
      regression model was used to determine differences in forearm kinematics and
      kinetics when pitching a fastball compared with a curveball, as well as to
      determine if associations existed between forearm supination and pronation
      moments and the elbow varus moment. RESULTS: There were a number of significant
      differences in forearm position when pitching a fastball compared with a
      curveball, with the curveball producing a more supinated forearm position.
      Significant associations were found between increasing forearm supination moments
      and an increase in elbow varus moment for both the fastball and the curveball ( P
      = .002 and P < .001, respectively). For every 1-N.m increase in the supination
      moment, there was a 1-N.m and 1.1-N.m increase in the elbow varus moment for the
      fastball and curveball, respectively. CONCLUSION: The results demonstrated that
      the forearm position was not associated with the elbow varus moment. However, the
      supination moment was associated with the elbow varus moment. CLINICAL RELEVANCE:
      On the basis of these findings, pitching coaches and trainers can understand the
      implications of proper lower arm pitching mechanics in the later portion of the
      pitch cycle as a potential risk of injury and, therefore, can develop coaching
      strategies to reduce incorrect positioning, especially when players are pitching
      the curveball.

PMID- 29024602
TI  - Knockdown of CEMIP suppresses proliferation and induces apoptosis in colorectal
      cancer cells: downregulation of GRP78 and attenuation of unfolded protein
      response.
AB  - It has been suggested that cell migration inducing hyaluronan binding protein
      (CEMIP) contributes to the carcinogenesis of colorectal cancer (CRC). Cancer
      cells can adapt to endoplasmic reticulum (ER) stress by initiating an unfolded
      protein response (UPR). This study aimed to investigate whether CEMIP affects the
      UPR of CRC cells, with a focus on 78 kDa glucose-regulated protein (GRP78, a
      major ER chaperone). We found that knockdown of CEMIP inhibited cell
      proliferation and induced a G1 arrest in SW480 CRC cells. The levels of cyclin D1
      and cyclin E1 and phospho-retinoblastoma, which are known to promote the cell
      cycle progression from G0 or G1 into S phase, were decreased in CEMIP-silenced
      cells. CEMIP shRNA induced apoptosis and inhibited GRP78 expression in SW480 and
      Colo205 cells. The basal UPR of cancer cells was attenuated by CEMIP shRNA, as
      evidenced by the decreased expression of UPR sensors, protein kinase R-like
      endoplasmic reticulum kinase (PERK), inositol requiring enzyme 1 (IRE1), and
      activating transcription factor 6 (ATF6). Furthermore, CEMIP silencing sensitized
      CRC cells to thapsigargin-induced apoptosis. Our study demonstrates that the in
      vitro anti-proliferative and pro-apoptotic effects in CRC cells that were induced
      by silencing CEMIP may be associated with GRP78 repression and UPR attenuation.

PMID- 29024603
TI  - Exercise tolerance during muscle contractions below and above the critical torque
      in different muscle groups.
AB  - The objective of this study was to test the hypotheses that end-test torque (ET)
      (expressed as % maximal voluntary contraction; MVC) is higher for plantar flexors
      (PF) than knee extensors (KE) muscles, whereas impulse above ET (IET) is higher
      for KE than PF. Thus, we expected that exercise tolerance would be longer for KE
      than PF only during the exercise performed above ET. After the determination of
      MVC, 40 men performed two 5-min all-out tests to determine ET and IET. Eleven
      participants performed a further 4 intermittent isometric tests, to exhaustion,
      at ET + 5% and ET - 5%, and 1 test for KE at the exercise intensity (%MVC)
      corresponding to ET + 5% of PF. The IET (7243.2 +/- 1942.9 vs. 3357.4 +/- 1132.3
      N.m.s) and ET (84.4 +/- 24.8 vs. 73.9 +/- 19.5 N.m) were significantly lower in
      PF compared with KE. The exercise tolerance was significantly longer for PF
      (300.7 +/- 156.7 s) than KE (156.7 +/- 104.3 s) at similar %MVC (~60%), and
      significantly shorter for PF (300.7 +/- 156.7 s) than KE (697.0 +/- 243.7 s) at
      ET + 5% condition. However, no significant difference was observed for ET - 5%
      condition (KE = 1030.2 +/- 495.4 s vs. PF = 1028.3 +/- 514.4 s). Thus, the limit
      of tolerance during submaximal isometric contractions is influenced by absolute
      MVC only during exercise performed above ET, which seems to be explained by
      differences on both ET (expressed as %MVC) and IET values.

PMID- 29024605
TI  - Hip and Ankle Kinematics in Noncontact Anterior Cruciate Ligament Injury
      Situations: Video Analysis Using Model-Based Image Matching.
AB  - BACKGROUND: Detailed kinematic descriptions of real anterior cruciate ligament
      (ACL) injury situations are limited to the knee only. PURPOSE: To describe hip
      and ankle kinematics as well as foot position relative to the center of mass
      (COM) in ACL injury situations through use of a model-based image-matching (MBIM)
      technique. The distance between the projection of the COM on the ground and the
      base of support (BOS) (COM_BOS) normalized to the femur length was also
      evaluated. STUDY DESIGN: Descriptive laboratory study. METHODS: Ten ACL injury
      video sequences from women's handball and basketball were analyzed. Hip and ankle
      joint kinematic values were obtained by use of MBIM. RESULTS: The mean hip
      flexion angle was 51 degrees  (95% CI, 41 degrees  to 63 degrees ) at initial
      contact and remained constant over the next 40 milliseconds. The hip was
      internally rotated 29 degrees  (95% CI, 18 degrees  to 39 degrees ) at initial
      contact and remained unchanged for the next 40 milliseconds. All of the injured
      patients landed with a heel strike with a mean dorsiflexion angle of 2 degrees 
      (95% CI, -9 degrees  to 14 degrees ), before reaching a flatfooted position 20
      milliseconds later. The foot position was anterior and lateral to the COM in all
      cases. However, none of the results showed larger COM_BOS than 1.2, which has
      been suggested as a criterion for ACL injury risk. CONCLUSIONS: Hip kinematic
      values were consistent among the 10 ACL injury situations analyzed; the hip joint
      remained unchanged in a flexed and internally rotated position in the phase
      leading up to injury, suggesting that limited energy absorption took place at the
      hip. In all cases, the foot contacted the ground with the heel strike. However,
      relatively small COM_BOS distances were found, indicating that the anterior and
      lateral foot placement in ACL injury situations was not different from what can
      be expected in noninjury game situations.

PMID- 29024606
TI  - Role of the TSLP-DC-OX40L pathway in asthma pathogenesis and airway inflammation
      in mice.
AB  - This study aimed to explore the effect of the TSLP-DC-OX40L pathway in asthma
      pathogenesis and airway inflammation in mice. For this, 65 male BALF/c mice were
      distributed among the control, asthma, immunoglobulin G (IgG) + asthma (IgG, 500
      MUg/500 MUL, intratracheal injection of 50 MUL each time), LY294002 (OX40L
      inhibitor) + asthma (intratracheal injection of 2 mg/kg LY294002), and anti-TSLP
      + asthma (intratracheal injection of 500 MUg/500 MUL TSLP antibody, 50 MUL each
      time) groups. ELISA was applied to measure the serum levels of immunoglobulin E
      (IgE), ovalbumin (OVA)-sIgE, interleukin-4 (IL-4), IL-5, IL-13, and interferon
      gamma (IFN-gamma); flow cytometry was employed to detect Treg cells and dendritic
      cell (DC) and lymphopoiesis. RT-qPCR and Western blot assays were used to measure
      the levels of TSLP, OX40L, T-bet, GATA-3, NF-kappaB, p38, and ERK. Treatment with
      LY294002 and anti-TSLP resulted in increases in the numbers of total cells,
      eosinophils, neutrophils, and lymphocytes in the bronchoalveolar lavage fluid;
      total serum levels of IgE, OVA-sIgE, IL-4, IL-5, and IL-13; levels of DC cells;
      lymphopoiesis; and levels of TSLP, OX40L, GATA-3, NF-kappaB, p38, and ERK,
      whereas there were decreases in the levels of IFN-gamma and CD4+CD25+Treg cells;
      CD4+Foxp3+Treg cells; and T-bet. The TSLP-DC-OX40L pathway may contribute to
      asthma pathogenesis and airway inflammation by modulating the levels of
      CD4+CD25+Treg cells and inflammatory cytokines.

PMID- 29024604
TI  - The avian embryo as a model for fetal alcohol spectrum disorder.
AB  - Prenatal alcohol exposure (PAE) remains a leading preventable cause of structural
      birth defects and permanent neurodevelopmental disability. The chicken (Gallus
      gallus domesticus) is a powerful embryological research model, and was possibly
      the first in which the teratogenicity of alcohol was demonstrated.
      Pharmacologically relevant exposure to alcohol in the range of 20-70 mmol/L (20
      80 mg/egg) disrupt the growth of chicken embryos, morphogenesis, and behavior,
      and the resulting phenotypes strongly parallel those of mammalian models. The
      avian embryo's direct accessibility has enabled novel insights into the
      teratogenic mechanisms of alcohol. These include the contribution of IGF1
      signaling to growth suppression, the altered flow dynamics that reshape
      valvuloseptal morphogenesis and mediate its cardiac teratogenicity, and the
      suppression of Wnt and Shh signals thereby disrupting the migration, expansion,
      and survival of the neural crest, and underlie its characteristic craniofacial
      deficits. The genetic diversity within commercial avian strains has enabled the
      identification of unique loci, such as ribosome biogenesis, that modify
      vulnerability to alcohol. This venerable research model is equally relevant for
      the future, as the application of technological advances including CRISPR,
      optogenetics, and biophotonics to the embryo's ready accessibility creates a
      unique model in which investigators can manipulate and monitor the embryo in real
      time to investigate the effect of alcohol on cell fate.

PMID- 29024607
TI  - Development of an Automatic Puncturing and Sampling System for a Self-Monitoring
      Blood Glucose Device.
AB  - BACKGROUND: Performing self-monitoring of blood glucose (SMBG) is a clinical
      challenge for elderly people with low dexterity. An all-in-one-type SMBG device
      that can simply and easily puncture and monitor would be useful for them. We
      developed an automatic skin-puncturing and blood-sampling (APS) system for
      introducing of an all-in-one-type SMBG device. The aims of this study were to
      determine if the developed APS system, which has automatic puncturing, squeezing,
      and application functions, could provide sufficient blood sample volumes for SMBG
      and to determine the factors associated with failure in the use of the system by
      adult volunteers. METHODS: We investigated the success rate of obtaining a 0.8
      MUL sample volume using the APS system and determined the factors associated with
      failure in 140 adult volunteers. The participant characteristics, induration of
      puncturing sites, and states of finger grip conditions were evaluated as factors
      of a puncturing failure. The participant characteristics, skin hydration, states
      of finger grip, skin elasticity of the finger pad, and blood flow were evaluated
      as factors of a squeezing failure. RESULTS: The success rate was 61.9%.
      Puncturing failure was 21.6%, and squeezing failure was 16.5%. Automatic
      puncturing factors associated with failure were male sex, larger finger diameter,
      and thicker finger pad. The only squeezing failure factor was lower peripheral
      skin temperature. CONCLUSIONS: Improvement of the finger station groove shape to
      prevent ischemia and the squeezing angle would be useful developments of the all
      in-one-type SMBG device for elderly people with decreased dexterity.

PMID- 29024608
TI  - Erastin-Like Anti-Warburg Agents Prevent Mitochondrial Depolarization Induced by
      Free Tubulin and Decrease Lactate Formation in Cancer Cells.
AB  - In Warburg metabolism, suppression of mitochondrial metabolism contributes to a
      low cytosolic ATP/ADP ratio favoring enhanced aerobic glycolysis. Flux of
      metabolites across the mitochondrial outer membrane occurs through voltage
      dependent anion channels (VDAC). In cancer cells, free dimeric tubulin induces
      VDAC closure and dynamically regulates mitochondrial membrane potential
      (DeltaPsi). Erastin, a small molecule that binds to VDAC, antagonizes the
      inhibitory effect of tubulin on VDAC and hyperpolarizes mitochondria in intact
      cells. Here, our aim was to identify novel compounds from the ChemBridge DIVERSet
      library that block the inhibitory effect of tubulin on DeltaPsi using cell-based
      screening. HCC4006 cells were treated with nocodazole (NCZ) to increase free
      tubulin and decrease DeltaPsi in the presence or absence of library compounds.
      Tetramethylrhodamine methylester (TMRM) fluorescence was assessed by high-content
      imaging to determine changes in DeltaPsi. Compounds were considered positive if
      DeltaPsi increased in the presence of NCZ. Using confocal microscopy, we
      identified and validated six lead molecules that antagonized the depolarizing
      effect of NCZ. Lead compounds and erastin did not promote microtubule
      stabilization, so changes in DeltaPsi were independent of tubulin dynamics. The
      most potent lead compound also decreased lactate formation. These novel small
      molecules represent a potential new class of anti-Warburg drugs.

PMID- 29024609
TI  - The Goldwater Rule: Perspectives From, and Implications for, Psychological
      Science.
AB  - When, if ever, should psychological scientists be permitted to offer professional
      opinions concerning the mental health of public figures they have never directly
      examined? This contentious question, which attracted widespread public attention
      during the 1964 U.S. presidential election involving Barry Goldwater, received
      renewed scrutiny during and after the 2016 U.S. presidential campaign, when many
      mental health professionals raised pointed questions concerning the psychiatric
      status of Donald Trump. Although the Goldwater Rule prohibits psychiatrists from
      offering diagnostic opinions on individuals they have never examined, no
      comparable rule exists for psychologists. We contend that, owing largely to the
      Goldwater Rule's origins in psychiatry, a substantial body of psychological
      research on assessment and clinical judgment, including work on the questionable
      validity of unstructured interviews, the psychology of cognitive biases, and the
      validity of informant reports and of L (lifetime) data, has been overlooked in
      discussions of its merits. We conclude that although the Goldwater Rule may have
      been defensible several decades ago, it is outdated and premised on dubious
      scientific assumptions. We further contend that there are select cases in which
      psychological scientists with suitable expertise may harbor a "duty to inform,"
      allowing them to offer informed opinions concerning public figures' mental health
      with appropriate caveats.

PMID- 29024610
TI  - TOUGH: The Measure of Merit in Psychological Science.
AB  - Scientific careers depend largely on the evaluation of one's merit. Yet
      scientists agree that the measurement of merit is quite a complex endeavor. Some
      indicators exist, such as Hirsch's well-known h index, but none can fully capture
      the complexity of the notion of merit. We propose that the h factor should be
      complemented with additional useful measurements: the t, o, u, and g indexes.

PMID- 29024611
TI  - End-of-Life Care Conversations in Resident Care Conferences in Nursing Home
      Settings.

PMID- 29024612
TI  - Asynchronous Telepsychiatry: A Component of Stepped Integrated Care.
AB  - OBJECTIVE: Integrated behavioral healthcare models typically involve a range of
      consultation options for mental healthcare. Asynchronous telepsychiatry (ATP)
      consults may be an additional potential choice, so we are conducting a 5-year
      clinical trial comparing ATP with synchronous telepsychiatry (STP) consultations.
      METHODS: Patients referred by primary care providers are randomly assigned to one
      of the two treatment groups, ATP or STP. Clinical outcome, satisfaction, and
      economic data are being collected from patients for 2 years at 6-month intervals.
      RESULTS: Baseline characteristics for the first 158 patients and case examples of
      ATP are presented. CONCLUSION: Implementing ATP in existing integrated behavioral
      healthcare models could make mental healthcare more efficient.

PMID- 29024613
TI  - Remote Monitoring of Automated Peritoneal Dialysis Patients: Assessing Clinical
      and Economic Value.
AB  - BACKGROUND: For chronic kidney disease patients who progress to end-stage renal
      disease, survival is dependent on renal replacement therapy in the form of kidney
      transplantation or chronic dialysis. Peritoneal dialysis (PD), which can be
      performed at home, is both more convenient and less costly than hemodialysis that
      requires three 4-h visits per week to the dialysis facility and complicated
      equipment. Remote therapy management (RTM), technologies that collect medical
      information and transmit it to healthcare providers for patient management, has
      the potential to improve the outcomes of patients receiving automated peritoneal
      dialysis (APD) at home. OBJECTIVE: Estimate through a simulation study the
      potential impact of RTM on APD patients use of healthcare resources and costs in
      the United States, Germany, and Italy. METHODS: Twelve APD patient profiles were
      developed to reflect potential clinical scenarios of APD therapy. Two versions of
      each profile were created to simulate healthcare resource use, one assuming use
      of RTM and one with no RTM. Eleven APD teams (one nephrologist, one nurse)
      estimated resources that would be used. RESULTS: Results from U.S., German, and
      Italian clinicians found that RTM could avoid use of 59, 49, and 16 resources
      over the 12 profiles, respectively. Estimated reduced utilization across the
      three countries ranged from one to two hospitalizations, one to four home visits,
      two to five emergency room visits, and four to eight unplanned clinic visits.
      Total savings across all scenarios were $23,364 in the United States, $11,477 in
      Germany, and $7,088 in Italy. CONCLUSION: In a simulated environment, early
      intervention enabled by RTM reduced healthcare resource utilization and
      associated costs.

PMID- 29024614
TI  - Staphylococcus aureus Infections in German Patients with Type 2 Diabetes Mellitus
      after Orthopedic Surgery: Incidence, Risk Factors, and Clinical and Health
      Economic Outcomes.
AB  - BACKGROUND: This study assessed Staphylococcus aureus infection risk in patients
      with type 2 diabetes mellitus (T2DM) undergoing an orthopedic knee, hip, or spine
      surgery. PATIENTS AND METHODS: All patients with a diagnosis of T2DM in the
      period from 2010 to 2012 were identified from a German claims database. First
      inpatient knee, hip, or spine surgery was used as index date. Cumulative
      incidence of S. aureus infections was calculated for several time intervals. Risk
      factors were identified based on a multi-variable Cox regression analysis. A case
      control analysis was conducted to assess mortality, healthcare resource
      utilization, and healthcare costs of S. aureus. RESULTS: In total, 9,401 patients
      with T2DM underwent a knee, hip, or spine surgery. Mean age was 72.58 years,
      63.32% were female, and 1.08% experienced an S. aureus infection in the 365-day
      follow-up period. The difference in all-cause direct treatment costs per patient
      year between infected and non-infected patients was 24,437.50$. Mortality rates
      were 25.52% (S. aureus group) versus 5.22% (non-S. aureus group), based on a 365
      day follow-up. CONCLUSIONS: Staphylococcus aureus is associated with a
      substantial healthcare burden and high mortality. Effective infection control
      measures should be considered to reduce post-surgical S. aureus infection risk in
      patients with T2DM.

PMID- 29024615
TI  - Molecular confirmation of Hepatozoon canis in Mauritius.
AB  - In this study, Hepatozoon species was molecularly identified and characterized
      for the first time on the Indian Ocean island of Mauritius. Partial sequences of
      the 18S rRNA gene of the Hepatozoon isolates were analysed from three naturally
      infected dogs. The sequences of H. canis were similar to the 18S rRNA partial
      sequences (JX112783, AB365071 99%) from dog blood samples from West Indies and
      Nigeria. Our sequences were deposited in the GenBank database.

PMID- 29024616
TI  - Investigation of infectious reproductive pathogens of large ruminants: Are
      neosporosis, brucellosis, leptospirosis and BVDV of relevance in Lao PDR?
AB  - N. caninum, bovine viral diarrhoea virus, Brucella abortus and Leptospira
      interrogans serovar Hardjo are globally significant reproductive pathogens that
      cause abortion and reproductive loss in large ruminants. Prevalence information
      is lacking in Lao People's Democratic Republic (Laos) despite the poor
      reproductive performance of cattle and buffalo. Serological examination of frozen
      cattle (n=90) and buffalo (n=61) sera by commercially available enzyme-linked
      immunosorbent assays provided the first reported screening of some of these
      pathogens in Laos. Seroprevalence differed amongst these large ruminant species,
      with N. caninum, BVDV and L. interrogans serovar Hardjo antibodies found in 68.9%
      (95% CI+/-11.6), 4.9% (95% CI+/-5.4) and 3.3% (95% CI+/-4.5) of buffalo sera,
      respectively, and in 7.8% (95% CI+/-5.5), 10.0% (95% CI+/-6.2) and 22.2% (95%
      CI+/-8.6) of cattle sera, respectively. Buffalo sera had a significantly higher
      seroprevalence of N. caninum compared to cattle (p<0.001) and cattle sera had a
      significantly higher seroprevalence of L. interrogans serovar Hardjo compared to
      buffalo (p=0.003). Variability was also observed across provinces for N. caninum
      in buffalo (p=0.007) and for L. interrogans serovar Hardjo in cattle (p=0.071),
      suggesting provincial risk factors conducive to pathogen transmission. BVDV and
      N. caninum seropositivity were negatively associated in buffalo (p=0.018) and
      cattle (p=0.003). In buffalo, L. interrogans serovar Hardjo and BVDV
      seropositivity were associated (p=0.035, p=0.039). The identification of
      antibodies against three major abortifacient pathogens in Laos prompts further
      research to determine if infection is associated with low reproductive efficiency
      and the risk factors for infection. This is needed for the development of
      evidence based prevention strategies for improved large ruminant reproductive
      management among smallholders in Laos.

PMID- 29024617
TI  - STM2360 encodes a d-ornithine/d-lysine decarboxylase in Salmonella enterica
      serovar typhimurium.
AB  - STM2360 is a gene located in a small operon of undetermined function in
      Salmonella enterica serovar Typhimurium LT2. The amino acid sequence of STM2360
      shows significant similarity (~30% identity) to diaminopimelate decarboxylase
      (DapDC), a Fold III pyridoxal-5'-phosphate (PLP) dependent enzyme involved in l
      lysine biosynthesis. We have found that the protein coded by STM2360 has a
      previously undocumented catalytic activity, d-ornithine/d-lysine decarboxylase
      (DOKDC). The reaction products, cadaverine and putrescine, respectively, were
      identified by NMR and mass spectrometry. The substrate specificity of DOKDC is d
      Lysine > d-Ornithine. This is the first pyridoxal-5'-phosphate dependent
      decarboxylase identified to act on d-amino acids. STM2358, located in the same
      operon, has ornithine racemase activity. This suggests that the physiological
      substrate of the decarboxylase and the operon is ornithine. Homologs of STM2360
      with high sequence identity (>80%) are found in other common enterobacteria,
      including species of Klebsiella, Citrobacter, Vibrio and Hafnia, as well as
      Clostridium in the Firmicutes, and Pseudomonas.

PMID- 29024618
TI  - Association of serum asymmetric dimethylarginine, homocysteine, and l-arginine
      concentrations during early pregnancy with hypertensive disorders of pregnancy.
AB  - BACKGROUND: Our previous study suggested that a lower l-arginine level (<70MUM)
      at early gestation is associated with pregnancy-induced hypertension. The
      maternal asymmetric dimethylarginine (ADMA) and homocysteine (Hcy) concentrations
      also have been reported to be increased in hypertensive disorders of pregnancy
      (HDP). These molecules have a key role in metabolism of nitric oxide. The aim of
      this study is to determine the most useful predictor of HDP at early gestation.
      METHODS: The concentrations of ADMA and Hcy at each of three periods in normal
      pregnancy were determined, and the values compared between the normal pregnancy
      and HDP groups. Moreover, the possible risk factors for the development of HDP
      also were evaluated using a multivariate logistic regression model and propensity
      score (PS). RESULTS: The maternal ADMA concentration was significantly elevated
      with advance of gestational age, while Hcy concentration was decreased from early
      to mid-gestation and increased from mid- to late-gestation in normal pregnancy.
      The maternal Hcy concentration at early gestation was significantly higher in the
      HDP group compared to that in the normal group. A higher maternal Hcy level
      (>7.2MUM) in early pregnancy was independently associated with the development of
      HDP (PS-adjusted odds ratio=4.47, 95% confidence interval=1.51-12.82), as well as
      pre-pregnancy overweight [body mass index (BMI)>25kg/m2], primipara status, and a
      lower maternal l-arginine level (<70MUM). CONCLUSIONS: The risk factors, such as
      overweight (BMI>25kg/m2) before pregnancy, primipara status, higher Hcy
      (>7.2MUM), and lower l-arginine (<70MUM) concentration in early pregnancy, for
      development of HDP were detected.

PMID- 29024619
TI  - Korean pediatric reference intervals for FT4, TSH, and TPO Ab and the prevalence
      of thyroid dysfunction: A population-based study.
AB  - BACKGROUND: The appropriate age-related reference intervals for thyroid
      stimulating hormone (TSH) and free thyroxine (FT4) are important in interpreting
      the results of thyroid function tests in children and adolescents. However, these
      reference intervals are scanty. This study aimed to establish the reference
      intervals for FT4, TSH, and thyroid peroxidase antibody (TPO Ab), and identify
      the epidemiological prevalence of thyroid dysfunction in a Korean pediatric
      population. METHODS: The data from a sample of 2042 children and adolescents aged
      10-18years who underwent a nationwide Korean representative sampling and cross
      sectional survey with blood collection for a thyroid function test using an
      electrochemiluminescence immunoassay were evaluated. RESULTS: Based on the
      National Academy of Clinical Biochemistry (NACB) criteria, the median and range
      (2.5th - 97.5th percentile) for FT4 and TSH in total were 16.47pmol/L (12.61
      21.49pmol/L) and 2.48mIU/L (0.63-7.03mIU/L), respectively. Positive TPO Ab (3.1%)
      by NACB was >19.16kIU/L (boys) and >29.30kIU/L (girls) for adolescents aged 10
      18years. FT4 and TSH were associated with increasing and decreasing age,
      respectively. Boys' FT4 and girls' TPO Ab levels were greater than for the other
      sex, respectively. Using the new reference interval, overt hypothyroidism,
      subclinical hypothyroidism, subclinical hyperthyroidism, and overt
      hyperthyroidism were found in 0.5%, 2.1%, 1.3%, and 1.2%, respectively, of Korean
      children and adolescents. CONCLUSIONS: This study provides evidence-based age-
      and sex-specific reference intervals for thyroid hormones and autoantibodies, and
      identifies the current prevalence of thyroid dysfunction in a Korean pediatric
      group.

PMID- 29024620
TI  - Zinc oxide nanoparticles inhibit dimethylnitrosamine induced liver injury in rat.
AB  - Dimethylnitrosamine (DMN) is a potent hepatotoxic, carcinogenic and mutagenic
      compound. It induces massive liver cell necrosis and death in experimental
      animals. Several drugs have been tested in the past for their protective behavior
      against DMN toxicity. However, it is for the first time that therapeutic
      intervention of ZnONPs (zinc oxide nanoparticles) has been studied against its
      toxicity. Present results show that a post treatment of ZnONPs (50 mg/kg) to DMN
      (2 MUl/100 g body weight) treated rats reduces lipid peroxidation, oxidative
      stress and fibrosis in the liver. It diminishes serum ALT (alanine
      transaminases), AST (aspartate transaminases) and LDH (lactate dehydrogenase)
      showing improvement in liver function. Reduced values of proinflammatory
      cytokines viz. TNF-alpha and IL-12 also support its protective effects.
      Histopathological observations also indicate improvement in liver cell
      morphology. It is postulated that ZnONPs offer protection through selective
      toxicity to proliferating tissue including adenomatous islands formed in the
      liver. Zinc metallothionein (Zn-MT) induced by ZnONPs may also contribute in the
      amelioration of DMN induced toxic effects. Diminution of oxidative stress by
      ZnONPs remains to be the key mechanism involved in its protective effects.
      However, toxicity of ZnONPs in the liver needs to be monitored simultaneously.

PMID- 29024621
TI  - Is Atypical Swallowing Associated With Relapse in Orthognathic Patients? A
      Retrospective Study of 256 Patients.
AB  - PURPOSE: To determine the association of atypical swallowing (AS) with relapse in
      patients undergoing combined orthodontic and orthognathic treatment. MATERIALS
      AND METHODS: In this retrospective cohort study, the clinical data of all
      patients who underwent combined surgical and orthodontic treatment from 1998
      through 2015 at the University Hospital of Geneva (Geneva, Switzerland) were
      reviewed. The primary outcome variables were 1) AS and 2) post-treatment relapse.
      Other variables included, age, gender, dentofacial deformity (facial asymmetry,
      mandibular deficiency, mandibular excess, maxillary retrusion, open bite),
      surgical procedure performed (bilateral sagittal split osteotomy [BSSO] with or
      without Le Fort I osteotomy), and dental interocclusal relations according to
      Angle. RESULTS: Of the 256 patients investigated, 23 (9%) showed relapse at 1
      year after treatment. Multivariate analysis showed that AS status (before
      treatment, odds ratio [OR] = 9.44, P = .005; after treatment, OR = 56.17, P <
      .001; before and after treatment, OR = 20.49, P < .001) was significantly
      associated with relapse. The presence of a pretreatment open bite also was
      associated with an increased risk of relapse (OR = 0.04, P < .001) regardless of
      AS status. CONCLUSION: The present study showed that in orthognathic patients 1)
      AS was associated with relapse regardless of dentofacial deformity or surgical
      procedure performed and 2) AS can appear after treatment in patients who were
      initially free of it.

PMID- 29024622
TI  - Smoking-Cessation Efforts by US Adult Smokers with Medical Comorbidities.
AB  - BACKGROUND: Continued cigarette smoking by individuals with chronic medical
      diseases can adversely affect their symptoms, disease progression, and mortality.
      We assessed the association between medical comorbidities and smoking-cessation
      efforts among US adult smokers. METHODS: We analyzed cross-sectional data from
      12,494 past-year cigarette smokers aged >=18 years from Wave 1 (2013-2014) of the
      nationally representative Population Assessment of Tobacco and Health study. We
      assessed the association between self-reported medical comorbidities and past
      year quit attempts, use of evidence-based smoking-cessation treatment or
      electronic cigarettes, and successful smoking cessation using logistic
      regression, adjusting for sociodemographics, insurance status, geographic region,
      and having a past-year doctor visit. RESULTS: In the study sample, 39% were aged
      18 to 34 years, 45% were female, 70% were non-Hispanic white, and 48% reported
      >=1 comorbidity. Smokers with any comorbidity, compared with those without
      comorbidities, had higher odds of trying to quit (adjusted odds ratio, 1.19; 95%
      confidence interval, 1.08-1.30), but no higher likelihood of quitting success.
      Having more medical comorbidities was associated with increased odds of trying to
      quit. Smokers with a comorbidity used evidence-based treatment more often than
      smokers without comorbidities (43% vs 26%); use of e-cigarettes to quit was
      similar between smokers with and without comorbidities (27% vs 28%). CONCLUSIONS:
      Adult smokers with chronic medical diseases try to quit and use evidence-based
      tobacco-cessation treatment more often than smokers without comorbidities, but
      they are no more likely to quit, suggesting that their quit attempts are less
      likely to succeed. Smokers with medical comorbidities may require more intensive,
      prolonged, and repeated treatment to stop smoking.

PMID- 29024623
TI  - Acute Colitis in a Patient with Streptococcus pyogenes Bacteremia.

PMID- 29024624
TI  - Prognostic Impact of Mild Hypokalemia in Terms of Death and Stroke in the General
      Population-A Prospective Population Study.
AB  - BACKGROUND: Potassium supplementation reduces the risk of cardiovascular
      mortality and stroke in population studies; however, the prognostic impact of
      mild hypokalemia in the general population has not been thoroughly investigated.
      We aimed to investigate associations between mild hypokalemia and endpoints in
      the general population. METHODS: Participants (aged 48-76 years) from the general
      population study "Copenhagen City Heart Study" (n = 5916) were studied.
      Participants were divided into groups according to baseline values of plasma
      potassium (potassium): hypokalemia (<3.7 mmol/L, n = 758), normokalemia (3.7-4.5
      mmol/L, n = 4973), and high potassium (>4.5 mmol/L, n = 185). Hypokalemia was
      further divided as potassium <3.4 mmol/L and 3.4-3.6 mmol/L. The primary
      endpoints were all-cause mortality and nonfatal validated ischemic stroke. The
      secondary endpoint was acute myocardial infarction (AMI). We adjusted for
      conventional risk factors, diuretics, and atrial fibrillation at baseline.
      RESULTS: Mean potassium in the hypokalemic group was 3.5 mmol/L (range, 2.6-3.6
      mmol/L) and was associated (P < 0.05) with increased systolic blood pressure,
      higher CHA2DS2-VASc score, and increased use of diuretics as compared with
      normokalemia. Baseline atrial fibrillation was equally frequent across groups.
      Median follow-up-time was 11.9 years (Q1-Q3: 11.4-12.5 years). Hypokalemia was
      borderline associated with increased stroke risk in a multivariable Cox model
      (including adjustment for competing risk) as compared with normokalemia (hazard
      ratio [HR] 1.40; 95% confidence interval [CI], 1.00-1.98). The subgroup with
      potassium <3.4 mmol/L had higher stroke risk (HR 2.10; 95% CI, 1.19-3.73) and
      mortality risk (HR 1.32; 95% CI, 1.01-1.74) as compared with normokalemia.
      Hypokalemia was not associated with AMI, and no increased risk of mortality was
      seen with concomitant AMI and hypokalemia. No associations were seen with high
      potassium. CONCLUSION: In a general population mild hypokalemia is associated
      with increased stroke risk and, to a lesser degree, increased mortality risk.

PMID- 29024625
TI  - Effect of Health Plan Financial Incentive Offering on Employees with Prediabetes.
AB  - BACKGROUND: Prediabetes may be improved or reversed with lifestyle interventions.
      A worksite wellness program offering financial incentives for participation may
      be effective in improving the health of employees with prediabetes. We studied
      the effect of employee health plan financial incentives on health outcomes for
      employees with prediabetes. METHODS: We conducted a retrospective cohort study
      using electronic medical record data from January 2008 to December 2012. Our
      study participants were employees with prediabetes and propensity-matched non
      employees with prediabetes and commercial health insurance, all receiving care
      within one health system. Exposures included fixed annual financial incentives
      for program participation and later a premium discount divided between program
      participation and achievement of goals. We used longitudinal linear mixed models
      to assess yearly changes in glycosylated hemoglobin (HbA1c), weight, and low
      density lipoprotein cholesterol in employees versus non-employees. We also
      compared outcomes of employees by ever- versus never- program participant status.
      RESULTS: Our study population included 1005 employees and 1005 matched non
      employees. The yearly reduction in HbA1c for employees versus matched non
      employees did not differ in 2008-2010 but was greater in 2010-2012, when
      incentives were tied to program participation as well as achievement of goals (
      0.10% vs -0.08 %, respectively; P for difference in change [DIC] = .01 from 2010
      to 2012). Analyses from both periods showed that employees lost more weight per
      year than matched non-employees (-1.85 vs -0.21 lb [1 lb=0.45 kg] from 2008 to
      2010; P for DIC < .001 and -2.35 vs -0.65 lb from 2010 to 2012; P for DIC <
      .001). Employees who participated in disease management lost more weight than
      those who did not (-2.14 vs 0.79 lb yearly before 2010 and -2.82 vs -0.91 after
      January 1, 2010, P for DIC < .01 and < .001, respectively). CONCLUSION: A
      worksite wellness program offering health plan financial incentives for
      participation and outcomes was associated with improvements in weight and HbA1c.

PMID- 29024626
TI  - Patient with Gluten Encephalopathy Presenting with Neuropsychiatric Symptoms.

PMID- 29024627
TI  - Myostatin inhibits eEF2K-eEF2 by regulating AMPK to suppress protein synthesis.
AB  - Growth of skeletal muscle is dependent on the protein synthesis, and the rate of
      protein synthesis is mainly regulated in the stage of translation initiation and
      elongation. Myostatin, a member of the transforming growth factor-beta (TGF-beta)
      superfamily, is a negative regulator of protein synthesis. C2C12 myotubes was
      incubated with 0, 0.01, 0.1, 1, 2, 3 MUg/mL myostatin recombinant protein, and
      then we detected the rates of protein synthesis by the method of SUnSET. We found
      that high concentrations of myostatin (2 and 3 MUg/mL) inhibited protein
      synthesis by blocking mTOR and eEF2K-eEF2 pathway, while low concentration of
      myostatin (0.01, 0.1 and 1 MUg/mL) regulated eEF2K-eEF2 pathway activity to block
      protein synthesis without affected mTOR pathway, and myostatin inhibited eEF2K
      eEF2 pathway through regulating AMPK pathway to suppress protein synthesis. It
      provided a new mechanism for myostatin regulating protein synthesis and treating
      muscle atrophy.

PMID- 29024628
TI  - Biologico-clinical significance of DNMT3A variants expression in acute myeloid
      leukemia.
AB  - DNA methyltransferase 3A (DNMT3A) catalyzes de novo DNA methylation and plays
      important roles in the pathogenesis of acute myeloid leukemia. However, the
      expression status of DNMT3A variants in acute myeloid leukemia remains obscure.
      This study aimed to assess the expression levels of alternative splicing of
      DNMT3A variants and explore their roles in acute myeloid leukemia (AML). DNMT3A
      variants gene expression were assessed, measuring their effects on cell
      proliferation. In addition, the expression of DNMT3A variants were evaluated in
      acute myeloid leukemia patients. Four DNMT3A variants were identified, with
      DNMT3A1 and DNMT3A2V found to be dominant in acute myeloid leukemia cell lines.
      Moreover, DNMT3A2V overexpression delayed cell proliferation; while, DNMT3A2V
      R882H mutation promoted cell proliferation. Further, DNMT3A1 and DNMT3A2V were
      detected in newly diagnosed acute myeloid leukemia (AML) patients and controls
      with non-malignant hematological disease, with DNMT3A2V significantly up
      regulated in AML patients. The main transcript switched from DNMT3A1 to DNMT3A2V
      in some patients, especially the low risk group based on the NCCN 2016
      guidelines. These findings suggest that DNMT3A1 and DNMT3A2V are the main
      variants in acute myeloid leukemia with different clinical association, and might
      play important roles in the pathophysiology of acute myeloid leukemia.

PMID- 29024629
TI  - The role of WT1 isoforms in vasculogenic mimicry and metastatic potential of
      human triple negative breast cancer cells.
AB  - Triple negative breast cancer (TNBC) is highly aggressive and has a few
      therapeutic treatments, so new targeted therapy and biomarkers are required to
      provide alternative choices for treating TNBC patients. Recent studies showed
      that vasculogenic mimicry (VM), the formation of blood channels by aggressive
      cancer cells that mimic endothelial cells, is a factor contributing to poor
      prognosis in TNBC. Wilms' tumor 1 (WT1) gene has been found to be highly
      expressed in TNBC, and has 4 major distinct isoforms; isoform A (-17AA/-KTS; -/
      ), isoform B (+17AA/-KTS; +/-), isoform C (-17AA/+KTS; -/+) and isoform D
      (+17AA/+KTS; +/+). The involvement of each WT1 isoform in TNBC progression
      remains largely unclear. In this study, WT1 isoform-overexpressing cell sublines
      were established from a TNBC cell line, MDA-MB-231, by stable transfection, and
      the aggressive behavior of the cell sublines were evaluated. Only the WT1 isoform
      B- and isoform C-overexpressing cell sublines showed the significant increase in
      VM forming capability compared to the parental cell line and other isoform cell
      sublines. qRT-PCR was used to explore the change in expression level of two VM
      related genes, EphA2 and VE-cadherin. All WT1 isoform cell sublines showed up
      regulation of EphA2 but the levels detected in the isoform B- and isoform C-cell
      sublines were higher than those observed in other cell sublines. In contrast,
      significant up-regulation of VE-cadherin was found only in isoform A- and isoform
      D-cell sublines. Isoform B- and isoform C-cell sublines showed higher rates of
      cell migration compared to those of other cell sublines, as determined by both
      wound healing and Transwell assays. Gelatin zymography revealed increased MMP-9
      enzyme production in isoform D-cell subline compared to the parental cell line,
      but this change was not observed in other cell sublines. Western blot analysis
      showed significantly increased expression of beta-catenin in isoform B- and
      isoform C-cell sublines, compared to parental cell line and other isoform cell
      sublines. In conclusion, our findings demonstrate that WT1 isoforms play
      different roles in modulating the VM-forming capacity and metastatic potential of
      TNBC cells.

PMID- 29024630
TI  - Improved chemoradiation treatment using trifluridine in human colorectal cancer
      cells in vitro.
AB  - We aimed to assess the combined effect of trifluridine (FTD) and ionizing
      radiation (IR) on colorectal cancer cells in vitro. Colorectal cancer cells, HT
      29, HCT-15, and HCT 116, showing low, medium, and high sensitivity to IR,
      respectively, were treated with the combinations of FTD and IR, and evaluated by
      the clonogenic survival assay. The radiation dose modification factors (DMFs)
      were calculated as the ratio of radiation doses producing equivalent surviving
      fractions following the FTD/IR treatment, or IR alone. DMFs of 4 MUM FTD followed
      by 8 Gy of IR were 2.7, 1.5, and 1.2 for HT-29, HCT-15, and HCT 116,
      respectively, whereas those of 8 Gy of IR followed by FTD were 1.6, 1.4, and 1.0
      for these cells, respectively. Intracellular DNA double-strand break levels after
      IR and FTD were significantly higher than those observed following the IR
      treatment alone, regardless of whether the IR was applied before or after FTD.
      RAD51 expression levels were shown to be increased in FTD and IR treated cells.
      Apoptotic proteins, such as cleaved PARP and cleaved caspase-3, were detected in
      cells treated with the combination of FTD and IR, while their expression was not
      significantly induced after IR or FTD treatment alone. These findings suggest
      that FTD enhances the efficacy of IR and provide a rationale for designing novel
      combination chemoradiotherapy regimens containing FTD for patients with rectal
      cancer that are insensitive to the radiation treatment.

PMID- 29024631
TI  - Luteoloside induces G0/G1 arrest and pro-death autophagy through the ROS-mediated
      AKT/mTOR/p70S6K signalling pathway in human non-small cell lung cancer cell
      lines.
AB  - Autophagy has attracted a great deal of interest in tumour therapy research in
      recent years. However, the anticancer effect of luteoloside, a naturally
      occurring flavonoid isolated from the medicinal plant Gentiana macrophylla, on
      autophagy remains poorly understood in human lung cells. In the present study, we
      have investigated the anticancer effects of luteoloside on non-small cell lung
      cancer (NSCLC) cells and demonstrated that luteoloside effectively inhibited
      cancer cell proliferation, inducing G0/G1 phase arrest associated with reduced
      expression of CyclinE, CyclinD1 and CDK4; we further found that treatment with
      luteoloside did not strongly result in apoptotic cell death in NSCLC (A549 and
      H292) cells. Interestingly, luteoloside induced autophagy in lung cancer cells,
      which was correlated with the formation of autophagic vacuoles, breakdown of p62,
      and the overexpression of Beclin-1 and LC3-II, but not in a human bronchial
      epithelial cell line (BEAS-2B). Notably, pretreatment of cancer cells with 3-MA,
      an autophagy inhibitor, protected against autophagy and promoted cell viability
      but not apoptosis. To further clarify whether luteoloside-induced autophagy
      depended on the PI3K/AKT/mTOR/p70S6K signalling pathway, a major autophagy
      suppressive cascade, cells were treated with a combination of AKT inhibitor
      (LY294002) and mTOR inhibitor (Rap). These results demonstrated that luteoloside
      induced autophagy in lung cancer cell lines by inhibiting the pathway at p-Akt
      (Ser473), p-mTOR and p-p70S6K (Thr389). Moreover, we observed that luteoloside
      induced cell autophagy was correlated with production of reactive oxygen species
      (ROS). NAC-mediated protection against ROS clearly implicated ROS in the
      activation of autophagy and cell death. In addition, the results showed that ROS
      served as an upstream effector of the PI3K/AKT/mTOR/p70S6K pathway. Taken
      together, the present study provides new insights into the molecular mechanisms
      underlying luteoloside-mediated cell death in NSCLC cells and supports
      luteoloside as a potential anti-cancer agent for targeting NSCLC through the
      induction of autophagy, inhibition of proliferation and PI3K/AKT/mTOR/p70S6K
      signalling.

PMID- 29024632
TI  - Quantitative proteome analysis of bovine mammary gland reveals protein dynamic
      changes involved in peak and late lactation stages.
AB  - Mammary gland is an important organ for milk synthesis and secretion. It
      undergoes dramatic physiological changes to adapt the shift from peak to late
      lactation stage. Protein plays a final very vital role in many life functions,
      and the protein changes during different lactation stages potentially reflect the
      biology of lactation and the functions of mammary gland in cows. In current
      study, we adopted tandem mass tags label-based quantitative analysis technique
      and to investigate proteome changes occurring in bovine mammary gland from peak
      to late lactation stages. A total of 3753 proteins from mammary tissues taken at
      two lactation points from four individual cows by biopsy were quantified, out of
      which 179 proteins were expressed differentially between two stages. We observed
      five new DEPs (AACS, DHCR7, GSTM3, SFRP1 and SFRP4) and nine functional well
      studies known proteins (PLIN2, LPIN1, PLIN3, GSN, CD74, MMP2, SOD1, SOD3 and
      GPX3) related to milk performance and mammary morphology. Bioinformatics analyses
      of the DEPs showed a majority of the up-regulated proteins during late lactation
      stage were related to apoptosis and immune process, while the downregulated
      proteins were mainly involved in localization, lipid metabolic and transport
      process. This suggests that the mammary gland can adapt to different molecular
      functions according to the biological need of the animal. From the integrated
      analysis of the differentially expressed proteins with known quantitative trait
      loci and genome-wide association study data, we identified 95 proteins may
      potentially affect milking performance. We expect findings in this study could be
      a valuable resource for future studies investigating the bovine proteome and
      functional studies.

PMID- 29024633
TI  - The Healthy and Diseased Microenvironments Regulate Oligodendrocyte Properties:
      Implications for Regenerative Medicine.
AB  - White matter disorders are characterized by deficient myelin or myelin loss, lead
      to a range of neurologic dysfunctions, and can result in early death.
      Oligodendrocytes, which are responsible for white matter formation, are the first
      targets for treatment. However, many studies indicate that failure of white
      matter repair goes beyond the intrinsic incapacity of oligodendrocytes to
      (re)generate myelin and that failed interactions with neighboring cells or
      factors in the diseased microenvironment can underlie white matter defects.
      Moreover, most of the white matter disorders show specific white matter pathology
      caused by different disease mechanisms. Herein, we review the factors within the
      cellular and the extracellular microenvironment regulating oligodendrocyte
      properties and discuss stem cell tools to identify microenvironmental factors of
      importance to the development of improved regenerative medicine for patients with
      white matter disorders.

PMID- 29024635
TI  - Keeping Time in a Relay Race for Fat.
AB  - Gut microbes impact host metabolism via a multitude of mechanisms, including
      through host circadian rhythm regulation. How microbes influence host circadian
      networks remains unclear. Recently, Wang et al. (2017) showed that crosstalk
      between specific microbial components and innate immune cells tunes epithelial
      circadian oscillations via Nfil3, modulating lipid uptake and metabolism.

PMID- 29024636
TI  - IFN-Lambda: The Key to Norovirus's Secret Hideaway.
AB  - The cellular tropism of noroviruses in immune-competent hosts remains enigmatic.
      In recent studies in Cell Host & Microbe and Immunity, Lee et al. (2017) and
      Tomov et al. (2017) determine that norovirus innate immune evasion enables
      infection of intestinal epithelial cells, escape from adaptive immunity, virus
      persistence, and shedding.

PMID- 29024637
TI  - Pla2g1b Places Worms in Peril.
AB  - The determinants of helminth resistance are not well understood. In this issue of
      Cell Host & Microbe, Entwistle et al. (2017) provide intriguing evidence that a
      phospholipase A2 (Pla2gb1) produced by epithelial cells can impair larval
      development in helminths, providing a novel mechanism contributing to intestinal
      nematode resistance.

PMID- 29024634
TI  - Space Invaders: Brain Tumor Exploitation of the Stem Cell Niche.
AB  - Increasing evidence indicates that the adult neurogenic niche of the ventricular
      subventricular zone (V-SVZ), beyond serving as a potential site of origin,
      affects the outcome of malignant brain cancers. Glioma contact with this niche
      predicts worse prognosis, suggesting a supportive role for the V-SVZ environment
      in tumor initiation or progression. In this review, we describe unique components
      of the V-SVZ that may permit or promote tumor growth within the region. Cell-cell
      interactions, soluble factors, and extracellular matrix composition are
      discussed, and the role of the niche in future therapies is explored. The purpose
      of this review is to highlight niche intrinsic factors that may promote or
      support malignant cell growth and maintenance, and point out how we might
      leverage these features to improve patient outcome.

PMID- 29024638
TI  - Shigella Stays on the Move.
AB  - Guanylate-binding proteins (GBPs) confer protection against intracellular
      pathogens. In this issue of Cell Host & Microbe, Wandel et al. (2017) report that
      cytosolic Shigella becomes trapped within a GBP coat that prevents bacterial cell
      to-cell spread. However, this defense mechanism is counteracted by the bacterial
      E3 ubiquitin ligase IpaH9.8.

PMID- 29024639
TI  - Helicobacter pylori Makes a Molecular Incision to Gain Epithelial Entry.
AB  - Helicobacter pylori type IV secretion system injects the oncoprotein CagA into
      epithelial cells to drive carcinogenesis. In this issue of Cell Host & Microbe,
      Tegtmeyer et al. (2017) show that a secreted bacterial protease disrupts apical
      junctional complexes, paving the way for H. pylori to access the basolateral
      compartment and trigger pathogenesis.

PMID- 29024640
TI  - Sociovirology: Conflict, Cooperation, and Communication among Viruses.
AB  - Viruses are involved in various interactions both within and between infected
      cells. Social evolution theory offers a conceptual framework for how virus-virus
      interactions, ranging from conflict to cooperation, have evolved. A critical
      examination of these interactions could expand our understanding of viruses and
      be exploited for epidemiological and medical interventions.

PMID- 29024641
TI  - Diverse Viruses Require the Calcium Transporter SPCA1 for Maturation and Spread.
AB  - Respiratory and arthropod-borne viral infections are a global threat due to the
      lack of effective antivirals and vaccines. A potential strategy is to target host
      proteins required for viruses but non-essential for the host. To identify such
      proteins, we performed a genome-wide knockout screen in human haploid cells and
      identified the calcium pump SPCA1. SPCA1 is required by viruses from the
      Paramyxoviridae, Flaviviridae, and Togaviridae families, including measles,
      dengue, West Nile, Zika, and chikungunya viruses. Calcium transport activity is
      required for SPCA1 to promote virus spread. SPCA1 regulates proteases within the
      trans-Golgi network that require calcium for their activity and are critical for
      virus glycoprotein maturation. Consistent with these findings, viral
      glycoproteins fail to mature in SPCA1-deficient cells preventing viral spread,
      which is evident even in cells with partial loss of SPCA1. Thus, SPCA1 is an
      attractive antiviral host target for a broad spectrum of established and emerging
      viral infections.

PMID- 29024644
TI  - M. tuberculosis-Induced Necrosis of Infected Neutrophils Promotes Bacterial
      Growth Following Phagocytosis by Macrophages.
AB  - Neutrophils represent the main infected cell population in the lungs of active
      tuberculosis patients. Efficient removal of infected and dying neutrophils is
      required to protect the surrounding tissue from bioactive neutrophil molecules
      and subsequent pathological sequelae. While the removal of apoptotic M.
      tuberculosis (Mtb)-infected cells, or efferocytosis, is considered beneficial for
      host defense, little is known about Mtb-infected necrotic neutrophils. We found
      that Mtb induces necrosis of human neutrophils in an ESX-1-dependent manner, and
      neutrophil-produced reactive oxygen species (ROS) drive this necrosis. Neutrophil
      necrosis was required for Mtb growth after uptake of infected neutrophils by
      human macrophages. Pharmacological inhibition of ROS production could prevent
      necrosis and restore the capability of macrophages to control Mtb growth, thereby
      identifying a potential host-directed therapy target. Taken together, necrosis
      represents the starting point for a vicious cycle including the uptake of
      infected necrotic cells by other phagocytes, Mtb growth therein, and sustained
      infection.

PMID- 29024642
TI  - Epithelial-Cell-Derived Phospholipase A2 Group 1B Is an Endogenous Anthelmintic.
AB  - Immunity to intestinal helminth infections has been well studied, but the
      mechanism of helminth killing prior to expulsion remains unclear. Here we
      identify epithelial-cell-derived phospholipase A2 group 1B (PLA2g1B) as a host
      derived endogenous anthelmintic. PLA2g1B is elevated in resistant mice and is
      responsible for killing tissue-embedded larvae. Despite comparable activities of
      other essential type-2-dependent immune mechanisms, Pla2g1b-/- mice failed to
      expel the intestinal helminths Heligmosomoides polygyrus or Nippostrongylus
      brasiliensis. Expression of Pla2g1b by epithelial cells was dependent upon
      intestinal microbiota, adaptive immunity, and common-gamma chain-dependent
      signaling. Notably, Pla2g1b was downregulated in susceptible mice and inhibited
      by IL-4R-signaling in vitro, uncoupling parasite killing from expulsion
      mechanisms. Resistance was restored in Pla2g1b-/- mice by treating infective H.
      polygyrus L3 larvae with PLA2g1B, which reduced larval phospholipid abundance.
      These findings uncover epithelial-cell-derived Pla2g1b as an essential mediator
      of helminth killing, highlighting a previously overlooked mechanism of anti
      helminth immunity.

PMID- 29024645
TI  - Helicobacter pylori Employs a Unique Basolateral Type IV Secretion Mechanism for
      CagA Delivery.
AB  - The Helicobacter pylori (Hp) type IV secretion system (T4SS) forms needle-like
      pili, whose binding to the integrin-beta1 receptor results in injection of the
      CagA oncoprotein. However, the apical surface of epithelial cells is exposed to
      Hp, whereas integrins are basolateral receptors. Hence, the mechanism of CagA
      delivery into polarized gastric epithelial cells remains enigmatic. Here, we
      demonstrate that T4SS pilus formation during infection of polarized cells occurs
      predominantly at basolateral membranes, and not at apical sites. Hp accomplishes
      this by secreting another bacterial protein, the serine protease HtrA, which
      opens cell-to-cell junctions through cleaving epithelial junctional proteins
      including occludin, claudin-8, and E-cadherin. Using a genetic system expressing
      a peptide inhibitor, we demonstrate that HtrA activity is necessary for
      paracellular transmigration of Hp across polarized cell monolayers to reach
      basolateral membranes and inject CagA. The contribution of this unique signaling
      cascade to Hp pathogenesis is discussed.

PMID- 29024643
TI  - GBPs Inhibit Motility of Shigella flexneri but Are Targeted for Degradation by
      the Bacterial Ubiquitin Ligase IpaH9.8.
AB  - Interferon exposure boosts cell-autonomous immunity for more efficient pathogen
      control. But how interferon-enhanced immunity protects the cytosol against
      bacteria and how professionally cytosol-dwelling bacteria avoid clearance are
      insufficiently understood. Here we demonstrate that the interferon-induced GTPase
      family of guanylate-binding proteins (GBPs) coats Shigella flexneri in a
      hierarchical manner reliant on GBP1. GBPs inhibit actin-dependent motility and
      cell-to-cell spread of bacteria but are antagonized by IpaH9.8, a bacterial
      ubiquitin ligase secreted into the host cytosol. IpaH9.8 ubiquitylates GBP1,
      GBP2, and GBP4 to cause the proteasome-dependent destruction of existing GBP
      coats. This ubiquitin coating of Shigella favors the pathogen as it liberates
      bacteria from GBP encapsulation to resume actin-mediated motility and cell-to
      cell spread. We conclude that an important function of GBP recruitment to S.
      flexneri is to prevent the spread of infection to neighboring cells while IpaH9.8
      helps bacterial propagation by counteracting GBP-dependent cell-autonomous
      immunity.

PMID- 29024647
TI  - Exciting Times Ahead.

PMID- 29024648
TI  - Mapping Brain Activity onto Molecularly Defined Cells.
AB  - The brain processes information and generates behavior by employing a wide array
      of different cell types. In this issue of Neuron, Wu et al. (2017) report a novel
      method that enables the efficient identification of molecularly defined cells
      that participate in a specific brain function.

PMID- 29024649
TI  - Obsessing about Uncertainty?
AB  - A striking observation in obsessive-compulsive disorder is that patients know
      that their obsessions and compulsions are excessive, but their symptoms
      nevertheless persist. Drawing on computational models from basic neuroscience,
      Vaghi and colleagues (2017) suggest a quantitative account of this clinical
      finding.

PMID- 29024650
TI  - A Corticostriatal Balancing Act Supports Skill Learning.
AB  - In this issue of Neuron, Kupferschmidt et al. (2017) reveal the shifting dynamics
      of functionally defined corticostriatal pathways during skill learning in mice
      using fiber photometry. They show different time courses in plasticity of
      associative and sensorimotor circuits across learning that involve changes at
      both the synaptic and cortical level.

PMID- 29024651
TI  - Implicit and Explicit Learning Mechanisms Meet in Monkey Prefrontal Cortex.
AB  - In this issue, Loonis et al. (2017) provide the first description of unique
      synchrony patterns differentiating implicit and explicit forms of learning in
      monkey prefrontal networks. Their results have broad implications for how
      prefrontal networks integrate the two learning mechanisms to control behavior.

PMID- 29024646
TI  - The Epstein-Barr Virus Regulome in Lymphoblastoid Cells.
AB  - Epstein-Barr virus (EBV) transforms B cells to continuously proliferating
      lymphoblastoid cell lines (LCLs), which represent an experimental model for EBV
      associated cancers. EBV nuclear antigens (EBNAs) and LMP1 are EBV transcriptional
      regulators that are essential for LCL establishment, proliferation, and survival.
      Starting with the 3D genome organization map of LCL, we constructed a
      comprehensive EBV regulome encompassing 1,992 viral/cellular genes and enhancers.
      Approximately 30% of genes essential for LCL growth were linked to EBV enhancers.
      Deleting EBNA2 sites significantly reduced their target gene expression.
      Additional EBV super-enhancer (ESE) targets included MCL1, IRF4, and EBF. MYC ESE
      looping to the transcriptional stat site of MYC was dependent on EBNAs. Deleting
      MYC ESEs greatly reduced MYC expression and LCL growth. EBNA3A/3C altered
      CDKN2A/B spatial organization to suppress senescence. EZH2 inhibition decreased
      the looping at the CDKN2A/B loci and reduced LCL growth. This study provides a
      comprehensive view of the spatial organization of chromatin during EBV-driven
      cellular transformation.

PMID- 29024652
TI  - Nuclear Pore Protein Meets Transcription Factor in Neural Fate.
AB  - How nuclear architecture contributes to transcriptional regulation in neural
      progenitor cells (NeuPCs) is poorly understood. A study by Toda et al. (2017) now
      shows that the nuclear pore protein Nup153 associates with the Sox2 transcription
      factor in the regulation of NeuPC maintenance and neural fate.

PMID- 29024653
TI  - Hazards to Early Development: The Biological Embedding of Early Life Adversity.
AB  - The number of children under 18 years of age has increased worldwide over the
      past decade. This growth spurt is due, in part, to remarkable progress in child
      survival. Alas, surviving early hazards, like prematurity or infectious disease,
      does not guarantee that children's development will not be compromised by other
      hazards as they grow older. Throughout the world, children continue to be
      confronted with a large number of biological and psychosocial challenges that
      greatly limit their developmental potential. The focus of this article is how
      such adverse experiences impact the developing brain.

PMID- 29024656
TI  - Diagnosing the Neural Circuitry of Reading.
AB  - We summarize the current state of knowledge of the brain's reading circuits, and
      then we describe opportunities to use quantitative and reproducible methods for
      diagnosing these circuits. Neural circuit diagnostics-by which we mean
      identifying the locations and responses in an individual that differ
      significantly from measurements in good readers-can help parents and educators
      select the best remediation strategy. A sustained effort to develop and share
      diagnostic methods can support the societal goal of improving literacy.

PMID- 29024657
TI  - Detecting Activated Cell Populations Using Single-Cell RNA-Seq.
AB  - Single-cell RNA sequencing offers a promising opportunity for probing cell types
      mediating specific behavioral functions and the underlying molecular programs.
      However, this has been hampered by a long-standing issue in transcriptional
      profiling of dissociated cells, specifically the transcriptional perturbations
      that are artificially induced during conventional whole-cell dissociation
      procedures. Here, we develop Act-seq, which minimizes artificially induced
      transcriptional perturbations and allows for faithful detection of both baseline
      transcriptional profiles and acute transcriptional changes elicited by
      behavior/experience-driven activity. Using Act-seq, we provide the first detailed
      molecular taxonomy of distinct cell types in the amygdala. We further show that
      Act-seq robustly detects seizure-induced acute gene expression changes in
      multiple cell types, revealing cell-type-specific activation profiles.
      Furthermore, we find that acute stress preferentially activates neuronal
      subpopulations that express the neuropeptide gene Cck. Act-seq opens the way for
      linking physiological stimuli with acute transcriptional dynamics in specific
      cell types in diverse complex tissues.

PMID- 29024655
TI  - Lost in Transportation: Nucleocytoplasmic Transport Defects in ALS and Other
      Neurodegenerative Diseases.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative
      disease characterized by degeneration of upper and lower motor neurons in the
      brain and spinal cord. The hallmark pathological feature in most cases of ALS is
      nuclear depletion and cytoplasmic accumulation of the protein TDP-43 in
      degenerating neurons. Consistent with this pattern of intracellular protein
      redistribution, impaired nucleocytoplasmic trafficking has emerged as a mechanism
      contributing to ALS pathology. Dysfunction in nucleocytoplasmic transport is also
      an emerging theme in physiological aging and other related neurodegenerative
      diseases, such as Huntington's and Alzheimer's diseases. Here we review transport
      through the nuclear pore complex, pointing out vulnerabilities that may underlie
      ALS and potentially contribute to this and other age-related neurodegenerative
      diseases.

PMID- 29024654
TI  - Striatal Local Circuitry: A New Framework for Lateral Inhibition.
AB  - This Perspective will examine the organization of intrastriatal circuitry, review
      recent findings in this area, and discuss how the pattern of connectivity between
      striatal neurons might give rise to the behaviorally observed synergism between
      the direct/indirect pathway neurons. The emphasis of this Perspective is on the
      underappreciated role of lateral inhibition between striatal projection cells in
      controlling neuronal firing and shaping the output of this circuit. We review
      some classic studies in combination with more recent anatomical and functional
      findings to lay out a framework for an updated model of the intrastriatal lateral
      inhibition, where we explore its contribution to the formation of functional
      units of processing and the integration and filtering of inputs to generate motor
      patterns and learned behaviors.

PMID- 29024658
TI  - Functional Convergence at the Retinogeniculate Synapse.
AB  - Precise connectivity between retinal ganglion cells (RGCs) and thalamocortical
      (TC) relay neurons is thought to be essential for the transmission of visual
      information. Consistent with this view, electrophysiological measurements have
      previously estimated that 1-3 RGCs converge onto a mouse geniculate TC neuron.
      Recent advances in connectomics and rabies tracing have yielded much higher
      estimates of retinogeniculate convergence, although not all identified contacts
      may be functional. Here we use optogenetics and a computational simulation to
      determine the number of functionally relevant retinogeniculate inputs onto TC
      neurons in mice. We find an average of ten RGCs converging onto a mature TC
      neuron, in contrast to >30 inputs before developmental refinement. However, only
      30% of retinogeniculate inputs exceed the threshold for dominating postsynaptic
      activity. These results signify a greater role for the thalamus in visual
      processing and provide a functional perspective of anatomical connectivity data.

PMID- 29024659
TI  - Posterior Cingulate Neurons Dynamically Signal Decisions to Disengage during
      Foraging.
AB  - Foraging for resources is a fundamental behavior balancing systematic search and
      strategic disengagement. The foraging behavior of primates is especially complex
      and requires long-term memory, value comparison, strategic planning, and decision
      making. Here we provide evidence from two different foraging tasks that neurons
      in primate posterior cingulate cortex (PCC) signal decision salience during
      foraging to motivate disengagement from the current strategy. In our foraging
      tasks, salience refers to the difference between decision thresholds and the net
      harvested reward. Salience signals were stronger in poor foraging contexts than
      rich ones, suggesting low harvest rates recruit mechanisms in PCC that regulate
      strategic disengagement and exploration during foraging.

PMID- 29024660
TI  - Amyloid Beta Peptides Block New Synapse Assembly by Nogo Receptor-Mediated
      Inhibition of T-Type Calcium Channels.
AB  - Compelling evidence links amyloid beta (Abeta) peptide accumulation in the brains
      of Alzheimer's disease (AD) patients with the emergence of learning and memory
      deficits, yet a clear understanding of the events that drive this synaptic
      pathology are lacking. We present evidence that neurons exposed to Abeta are
      unable to form new synapses, resulting in learning deficits in vivo. We
      demonstrate the Nogo receptor family (NgR1-3) acts as Abeta receptors mediating
      an inhibition of synapse assembly, plasticity, and learning. Live imaging studies
      reveal Abeta activates NgRs on the dendritic shaft of neurons, triggering an
      inhibition of calcium signaling. We define T-type calcium channels as a target of
      Abeta-NgR signaling, mediating Abeta's inhibitory effects on calcium, synapse
      assembly, plasticity, and learning. These studies highlight deficits in new
      synapse assembly as a potential initiator of cognitive pathology in AD, and
      pinpoint calcium dysregulation mediated by NgRs and T-type channels as key
      components. VIDEO ABSTRACT.

PMID- 29024661
TI  - Paclitaxel Reduces Axonal Bclw to Initiate IP3R1-Dependent Axon Degeneration.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect
      of many cancer treatments. The hallmark of CIPN is degeneration of long axons
      required for transmission of sensory information; axonal degeneration causes
      impaired tactile sensation and persistent pain. Currently the molecular
      mechanisms of CIPN are not understood, and there are no available treatments.
      Here we show that the chemotherapeutic agent paclitaxel triggers CIPN by altering
      IP3 receptor phosphorylation and intracellular calcium flux, and activating
      calcium-dependent calpain proteases. Concomitantly paclitaxel impairs axonal
      trafficking of RNA-granules and reduces synthesis of Bclw (bcl2l2), a Bcl2 family
      member that binds IP3R1 and restrains axon degeneration. Surprisingly, Bclw or a
      stapled peptide corresponding to the Bclw BH4 domain interact with axonal IP3R1
      and prevent paclitaxel-induced degeneration, while Bcl2 and BclxL cannot do so.
      Together these data identify a Bclw-IP3R1-dependent cascade that causes axon
      degeneration and suggest that Bclw-mimetics could provide effective therapy to
      prevent CIPN.

PMID- 29024663
TI  - Role of the Astroglial Glutamate Exchanger xCT in Ventral Hippocampus in
      Resilience to Stress.
AB  - We demonstrate that stress differentially regulates glutamate homeostasis in the
      dorsal and ventral hippocampus and identify a role for the astroglial xCT in
      ventral dentate gyrus (vDG) in stress and antidepressant responses. We provide an
      RNA-seq roadmap for the stress-sensitive vDG. The transcription factor REST binds
      to xCT promoter in co-occupancy with the epigenetic marker H3K27ac to regulate
      expression of xCT, which is also reduced in a genetic mouse model of inherent
      susceptibility to depressive-like behavior. Pharmacologically, modulating histone
      acetylation with acetyl-L-carnitine (LAC) or acetyl-N-cysteine (NAC) rapidly
      increases xCT and activates a network with mGlu2 receptors to prime an enhanced
      glutamate homeostasis that promotes both pro-resilient and antidepressant-like
      responses. Pharmacological xCT blockage counteracts NAC prophylactic effects.
      GFAP+-Cre-dependent overexpression of xCT in vDG mimics pharmacological actions
      in promoting resilience. This work establishes a mechanism by which vDG
      protection leads to stress resilience and antidepressant responses via epigenetic
      programming of an xCT-mGlu2 network.

PMID- 29024662
TI  - Loss of CLOCK Results in Dysfunction of Brain Circuits Underlying Focal Epilepsy.
AB  - Because molecular mechanisms underlying refractory focal epilepsy are poorly
      defined, we performed transcriptome analysis on human epileptogenic tissue.
      Compared with controls, expression of Circadian Locomotor Output Cycles Kaput
      (CLOCK) is decreased in epileptogenic tissue. To define the function of CLOCK, we
      generated and tested the Emx-Cre; Clockflox/flox and PV-Cre; Clockflox/flox mouse
      lines with targeted deletions of the Clock gene in excitatory and parvalbumin
      (PV)-expressing inhibitory neurons, respectively. The Emx-Cre; Clockflox/flox
      mouse line alone has decreased seizure thresholds, but no laminar or dendritic
      defects in the cortex. However, excitatory neurons from the Emx-Cre;
      Clockflox/flox mouse have spontaneous epileptiform discharges. Both neurons from
      Emx-Cre; Clockflox/flox mouse and human epileptogenic tissue exhibit decreased
      spontaneous inhibitory postsynaptic currents. Finally, video-EEG of Emx-Cre;
      Clockflox/flox mice reveals epileptiform discharges during sleep and also
      seizures arising from sleep. Altogether, these data show that disruption of CLOCK
      alters cortical circuits and may lead to generation of focal epilepsy.

PMID- 29024664
TI  - The Anterior Insular Cortex->Central Amygdala Glutamatergic Pathway Is Critical
      to Relapse after Contingency Management.
AB  - Despite decades of research on neurobiological mechanisms of psychostimulant
      addiction, the only effective treatment for many addicts is contingency
      management, a behavioral treatment that uses alternative non-drug reward to
      maintain abstinence. However, when contingency management is discontinued, most
      addicts relapse to drug use. The brain mechanisms underlying relapse after
      cessation of contingency management are largely unknown, and, until recently, an
      animal model of this human condition did not exist. Here we used a novel rat
      model, in which the availability of a mutually exclusive palatable food maintains
      prolonged voluntary abstinence from intravenous methamphetamine self
      administration, to demonstrate that the activation of monosynaptic glutamatergic
      projections from anterior insular cortex to central amygdala is critical to
      relapse after the cessation of contingency management. We identified the anterior
      insular cortex-to-central amygdala projection as a new addiction- and motivation
      related projection and a potential target for relapse prevention.

PMID- 29024665
TI  - Astrocyte-Secreted Glypican 4 Regulates Release of Neuronal Pentraxin 1 from
      Axons to Induce Functional Synapse Formation.
AB  - The generation of precise synaptic connections between developing neurons is
      critical to the formation of functional neural circuits. Astrocyte-secreted
      glypican 4 induces formation of active excitatory synapses by recruiting AMPA
      glutamate receptors to the postsynaptic cell surface. We now identify the
      molecular mechanism of how glypican 4 exerts its effect. Glypican 4 induces
      release of the AMPA receptor clustering factor neuronal pentraxin 1 from
      presynaptic terminals by signaling through presynaptic protein tyrosine
      phosphatase receptor delta. Pentraxin then accumulates AMPA receptors on the
      postsynaptic terminal forming functional synapses. Our findings reveal a
      signaling pathway that regulates synaptic activity during central nervous system
      development and demonstrates a role for astrocytes as organizers of active
      synaptic connections by coordinating both pre and post synaptic neurons. As
      mutations in glypicans are associated with neurological disorders, such as autism
      and schizophrenia, this signaling cascade offers new avenues to modulate synaptic
      function in disease.

PMID- 29024666
TI  - Dynamics of Gut-Brain Communication Underlying Hunger.
AB  - Communication between the gut and brain is critical for homeostasis, but how this
      communication is represented in the dynamics of feeding circuits is unknown. Here
      we describe nutritional regulation of key neurons that control hunger in vivo. We
      show that intragastric nutrient infusion rapidly and durably inhibits hunger
      promoting AgRP neurons in awake, behaving mice. This inhibition is proportional
      to the number of calories infused but surprisingly independent of macronutrient
      identity or nutritional state. We show that three gastrointestinal signals
      serotonin, CCK, and PYY-are necessary or sufficient for these effects. In
      contrast, the hormone leptin has no acute effect on dynamics of these circuits or
      their sensory regulation but instead induces a slow modulation that develops over
      hours and is required for inhibition of feeding. These findings reveal how layers
      of visceral signals operating on distinct timescales converge on hypothalamic
      feeding circuits to generate a central representation of energy balance.

PMID- 29024667
TI  - Parallel, but Dissociable, Processing in Discrete Corticostriatal Inputs Encodes
      Skill Learning.
AB  - Changes in cortical and striatal function underlie the transition from novel
      actions to refined motor skills. How discrete, anatomically defined
      corticostriatal projections function in vivo to encode skill learning remains
      unclear. Using novel fiber photometry approaches to assess real-time activity of
      associative inputs from medial prefrontal cortex to dorsomedial striatum and
      sensorimotor inputs from motor cortex to dorsolateral striatum, we show that
      associative and sensorimotor inputs co-engage early in action learning and
      disengage in a dissociable manner as actions are refined. Disengagement of
      associative, but not sensorimotor, inputs predicts individual differences in
      subsequent skill learning. Divergent somatic and presynaptic engagement in both
      projections during early action learning suggests potential learning-related in
      vivo modulation of presynaptic corticostriatal function. These findings reveal
      parallel processing within associative and sensorimotor circuits that challenges
      and refines existing views of corticostriatal function and expose neuronal
      projection- and compartment-specific activity dynamics that encode and predict
      action learning.

PMID- 29024668
TI  - Increased Prevalence of Calcium Transients across the Dendritic Arbor during
      Place Field Formation.
AB  - Hippocampal place cell ensembles form a cognitive map of space during exposure to
      novel environments. However, surprisingly little evidence exists to support the
      idea that synaptic plasticity in place cells is involved in forming new place
      fields. Here we used high-resolution functional imaging to determine the
      signaling patterns in CA1 soma, dendrites, and axons associated with place field
      formation when mice are exposed to novel virtual environments. We found that
      putative local dendritic spikes often occur prior to somatic place field firing.
      Subsequently, the first occurrence of somatic place field firing was associated
      with widespread regenerative dendritic events, which decreased in prevalence with
      increased novel environment experience. This transient increase in regenerative
      events was likely facilitated by a reduction in dendritic inhibition. Since
      regenerative dendritic events can provide the depolarization necessary for
      Hebbian potentiation, these results suggest that activity-dependent synaptic
      plasticity underlies the formation of many CA1 place fields.

PMID- 29024671
TI  - Baeyer-Villiger reaction of steroid sapogenins by CF3COOH-H2O2. A short cut to
      pregnan-3beta,16beta,20-triol 3-monoacetates.
AB  - Treatment of steroid sapogenins with H2O2 in CF3COOH for 15min followed by reflux
      in CH3OH/H2O afforded good yields of pregnan-3beta,16beta,20-triol 3
      monoacetates. When the hydrolysis step was carried out with KOH in refluxing
      methanol excellent yields pregnantriols were obtained. The resulting compounds
      were characterized by their melting points and NMR spectral data. An X-ray
      diffraction analysis of compound 3a confirmed the proposed structure and provided
      detailed information about the bond lengths, bond angles and conformation.

PMID- 29024669
TI  - Pyramidal Cell-Interneuron Circuit Architecture and Dynamics in Hippocampal
      Networks.
AB  - Excitatory control of inhibitory neurons is poorly understood due to the
      difficulty of studying synaptic connectivity in vivo. We inferred such
      connectivity through analysis of spike timing and validated this inference using
      juxtacellular and optogenetic control of presynaptic spikes in behaving mice. We
      observed that neighboring CA1 neurons had stronger connections and that
      superficial pyramidal cells projected more to deep interneurons. Connection
      probability and strength were skewed, with a minority of highly connected hubs.
      Divergent presynaptic connections led to synchrony between interneurons.
      Synchrony of convergent presynaptic inputs boosted postsynaptic drive.
      Presynaptic firing frequency was read out by postsynaptic neurons through short
      term depression and facilitation, with individual pyramidal cells and
      interneurons displaying a diversity of spike transmission filters. Additionally,
      spike transmission was strongly modulated by prior spike timing of the
      postsynaptic cell. These results bridge anatomical structure with physiological
      function.

PMID- 29024673
TI  - Not the usual suspect.
AB  - An 82-year-old woman presented with right-sided proptosis, chemosis, and a
      supraorbital bruit. A dural carotid-cavernous fistula was suspected, but catheter
      angiography revealed an intraorbital inferior ophthalmic vein arteriovenous
      fistula supplied by the right ophthalmic artery and infraorbital branch of the
      internal maxillary artery. A primary orbital arteriovenous fistula can mimic the
      clinical and radiographic features of the more common carotid-cavernous fistula.

PMID- 29024674
TI  - Optic nerve head problem.
AB  - A 68-year-old woman with a recent history of blurring in the left eye had
      undergone mastectomy for breast cancer 20 years ago. A series of bone metastases
      started 5 years after her diagnosis. Examination of the optic nerve head of the
      left eye revealed an isolated peripapillary mass. Indocyanine green angiography
      displayed vessels within the mass, and fluorescein angiography demonstrated
      hyperfluorescence of the mass from vascular leakage plus lobular spots of blocked
      fluorescence. B-scan ultrasound revealed a hyperechoic-elevated nodular mass on
      the optic disc. Spectral-domain optical coherence tomography displayed a mass of
      spherules. Magnetic resonance imaging of the brain demonstrated metastatic
      tumors. She was diagnosed with an optic disk metastasis from her breast
      carcinoma.

PMID- 29024670
TI  - A Meta-Analysis Suggests Different Neural Correlates for Implicit and Explicit
      Learning.
AB  - A meta-analysis of non-human primates performing three different tasks (Object
      Match, Category-Match, and Category-Saccade associations) revealed signatures of
      explicit and implicit learning. Performance improved equally following correct
      and error trials in the Match (explicit) tasks, but it improved more after
      correct trials in the Saccade (implicit) task, a signature of explicit versus
      implicit learning. Likewise, error-related negativity, a marker for error
      processing, was greater in the Match (explicit) tasks. All tasks showed an
      increase in alpha/beta (10-30 Hz) synchrony after correct choices. However, only
      the implicit task showed an increase in theta (3-7 Hz) synchrony after correct
      choices that decreased with learning. In contrast, in the explicit tasks,
      alpha/beta synchrony increased with learning and decreased thereafter. Our
      results suggest that explicit versus implicit learning engages different neural
      mechanisms that rely on different patterns of oscillatory synchrony.

PMID- 29024672
TI  - Conventional and real time RT-PCR assays for the detection and differentiation of
      variant rabbit hemorrhagic disease virus (RHDVb) and its recombinants.
AB  - Since its emergence, variant RHDV (RHDVb/RHDV2) has spread throughout the Iberian
      Peninsula aided by the apparent lack of cross protection provided by classic
      (genogroup 1; G1) strain derived vaccines. In addition to RHDVb, full-length
      genome sequencing of RHDV strains has recently revealed the circulation of
      recombinant viruses on the Iberian Peninsula. These recombinant viruses contain
      the RHDVb structural protein encoding sequences and the non-structural coding
      regions of either pathogenic RHDV-G1 strains or non-pathogenic (np) rabbit
      caliciviruses. The aim of the work was twofold: firstly to validate a diagnostic
      real time RT-PCR developed in 2012 for the detection of RHDVb strains and
      secondly, to design a conventional RT-PCR for the differentiation of RHDVb
      strains from RHDVb recombinants by subsequent sequencing of the amplicon.

PMID- 29024675
TI  - Tempo(ral) was the heart of the matter.
AB  - A 71-year-old woman was admitted with fever, headache, and weight loss associated
      with elevated inflammatory markers. She developed acute bilateral ophthalmoplegia
      and asymmetrical ptosis, rapidly followed by anterior ischemic optic neuropathy.
      Although the first temporal artery biopsy was negative, contralateral temporal
      artery biopsy revealed features consistent with giant cell arteritis. Even while
      under steroid therapy, she died a few days later from myocardial infarction.
      Acute bilateral complete ophthalmoplegia is a rare presentation of a limited
      number of possible diseases. Among these, giant cell arteritis should be
      suspected in the appropriate clinical scenario.

PMID- 29024676
TI  - Perinatal fluoxetine prevents the effect of pre-gestational maternal stress on 5
      HT in the PFC, but maternal stress has enduring effects on mPFC synaptic
      structure in offspring.
AB  - Maternal affective disorders are frequently treated with selective serotonin
      reuptake inhibitor medications (SSRIs); with up to 10% of women being prescribed
      these medications during pregnancy. Infant development depends on the early
      serotonergic environment, which is altered by perinatal SSRIs, raising concern
      about how these medications affect neural outcomes. While clinical and
      preclinical research suggests an impact of SSRIs on the developing brain, more
      research is needed to determine the effects on neuroplasticity, the serotonergic
      system, and the hypothalamic-pituitary-adrenal axis in neural regions mediating
      behavior. The current work investigated the effects of the SSRI, fluoxetine, on
      the serotonergic system in the prefrontal cortex (PFC) during pre-adolescence,
      and changes to synaptic markers and glucocorticoid receptor density in the
      cingulate cortex (medial PFC) of pre-adolescent and adult Sprague-Dawley male and
      female rats. To model aspects of Perinatal Depression and maternal anxiety, pre
      gestational maternal stress was used resulting in male and female offspring from
      4 groups: 1) control, 2) perinatal fluoxetine exposed, 3) pre-gestational
      maternal stress exposed, and 4) pre-gestational maternal stress + fluoxetine.
      Perinatal fluoxetine prevented the effects of maternal stress on 5-HT levels and
      5-HT turnover ratio in the PFC of pre-adolescent offspring, particularly in
      females. However, pre-gestational stress reduced synaptophysin and PSD-95
      densities in the cingulate cortex, effects that were more pronounced in males.
      Interestingly, perinatal fluoxetine exposure reduced GR density in adult males in
      this same brain area. Together, results show differential effects of perinatal
      SSRIs and pre-gestational maternal stress on neurodevelopment in the PFC of males
      and females.

PMID- 29024677
TI  - Eating behavior traits associated with demographic variables and implications for
      obesity outcomes in early childhood.
AB  - Despite ongoing investigation of children's eating behaviors to better understand
      the etiology of childhood obesity, few studies have aimed to determine
      differences in eating behavior based on psycho-social variables reflective of
      'stressful' life circumstance. Cross-sectional data collected from parents of 977
      Australian children (2.0-5.0 years) in an online survey was used to determine
      associations between parent-reported Children's Eating Behavior Questionnaire
      [CEBQ] sub-scales, child BMI z-scores and psycho-social variables. When examined
      individually, all CEBQ sub-scales, except Slowness in Eating, were associated
      with BMI z-score (Food Responsiveness B = 0.226, p = 0.003, Enjoyment of Food B =
      0.169, p = 0.035, Food Fussiness B = -0.139, p = 0.024, Satiety Responsiveness B
      = -0.318, p = 0.001). On examining CEBQ sub-scales along with psycho-social
      demographic variables, only Food Responsiveness and Satiety Responsiveness were
      retained, along with being a boy, child age, and parent BMI. Food Responsiveness
      was positively associated with parental stress and child age and negatively with
      parent BMI, while Enjoyment of Food was positively associated with child sleep
      duration, single parent status, and negatively with breastfeeding less than 6
      months and parental depression. Satiety Responsiveness was positively associated
      with parent BMI and child age, and negatively with child sleep duration, while
      Food Fussiness was positively associated with child age and breastfeeding less
      than 6 months, and negatively with sleep duration, parental depression and single
      parent status. Attention to eating behaviors and associated psycho-social
      variables may provide opportunity for targeted obesity prevention initiatives.

PMID- 29024678
TI  - Suppression of nucleocytoplasmic p27Kip1 export attenuates CDK4-mediated neuronal
      death induced by status epilepticus.
AB  - Aberrant cell cycle re-entry promotes neuronal death in various neurological
      diseases. Thus, cyclin-dependent kinases (CDKs) seem to be one of potential
      therapeutic targets to prevent neuronal loss. In the present study, we
      investigated the involvements of CDK4, CDK5 and p27Kip1 (an endogenous CDK
      inhibitor) in status epilepticus (SE)-induced neuronal death. Following SE, CDK4
      expression was increased in CA1 neurons, while CDK5 was decreased. Most of TUNEL
      positive neurons showed CDK4 expression, but less CDK5 expression. Flavopiridol
      (a CDK4 inhibitor) attenuated TUNEL signal and CDK4 expression in CA1 neurons
      following SE. CDK5 inhibitors did not affect these phenomena. Both flavopiridol
      and leptomycin B (an inhibitor of chromosome region maintenance 1) mitigated SE
      induced neuronal death by inhibiting nucleocytoplasmic p27Kip1 translocation.
      These findings suggest that SE may lead to nucleocytoplasmic p27Kip1 export that
      initiates CDK4, not CDK5, induction, which an abortive and fatal cell cycle re
      entry progress in CA1 neurons.

PMID- 29024680
TI  - Uridine attenuates morphine-induced conditioned place preference and regulates
      glutamate/GABA levels in mPFC of mice.
AB  - Several lines of evidence suggest that uridine, as a neuromodulator, plays an
      important role in drug addiction. We previously found that uridine circumvents
      morphine-induced behavioral sensitization by decreasing the extracellular
      dopamine levels in the dorsal striatum. In the present study, the effects of
      uridine on morphine-induced conditioned place preference (CPP) and the possible
      roles of glutamate and GABA in the stress-induced reinstatement of CPP were
      investigated. First, the effects of uridine (1, 10 and 100mg/kg, i.p.) on the
      four defined phases - acquisition, expression, extinction and reinstatement (drug
      priming and restraint stress) - of morphine-induced CPP were studied. The results
      showed that pretreatment with uridine significantly blocked the acquisition and
      expression phases of CPP. Additionally, uridine also facilitated CPP extinction
      and inhibited stress-induced CPP reinstatement, although it failed to affect drug
      induced CPP reinstatement. Since glutamatergic and GABAergic systems are both
      involved in CPP reinstatement, the extracellular levels of glutamate and GABA in
      the mPFC during the stress-induced CPP reinstatement were determined using in
      vivo microdialysis. The results showed that uridine attenuated the stress-induced
      glutamate increase in the mPFC without influencing the basal glutamate levels,
      and increased the levels of extracellular GABA in the mPFC both under normal
      physiological conditions and after the stress stimulus. Thus, our results
      indicate that uridine depresses the stress-induced reinstatement of CPP,
      simultaneously regulating glutamatergic and GABAergic neurotransmission in the
      mPFC. The present work provides further understanding of the role of uridine in
      morphine-induced neurobehavioral changes.

PMID- 29024681
TI  - Potentiation of morphine-induced antinociception and locomotion by citalopram is
      accompanied by anxiolytic-like effects.
AB  - Morphine and related opioids are the mainstay of analgesic treatment, especially
      in patients suffering chronic pain. Besides their antinociceptive effects they
      may also exhibit anxiolytic-like properties that could contribute to pain relief.
      The pharmacological manipulation of the serotonergic system may not only modulate
      pain transmission and processing but also other behavioral effects of opioids.
      The present study aimed to analyze the effect of the concurrent treatment with
      citalopram, a selective serotonin reuptake inhibitor, on the antinociceptive,
      locomotor and anxiety-related effects induced by acute and subchronic
      administration of morphine in mice. Citalopram (15mg/kg) enhanced the acute
      antinociceptive effects of morphine when concurrently administered as evidenced
      by a two-fold increase in the ED50 for the antinociceptive effect of morphine in
      the hot-plate test. Chronic studies also revealed that concurrent citalopram
      treatment (15mg/kg) delayed the development of tolerance to the thermal
      antinociceptive effects of morphine. Additionally, morphine-induced
      hyperlocomotion was potentiated by citalopram as assessed in the open-field test
      and in the spontaneous activity recording in the home cage, a behavioral outcome
      to which tolerance or desensitization was not developed. Interestingly, chronic
      administration of both drugs promoted an anxiolytic effect as evidenced by the
      increased central activity in the open field test. Future investigations on this
      pharmacological interaction, such as the possible translational research in
      clinics, might have consequences in future strategies for the therapeutic
      management of pain.

PMID- 29024679
TI  - Short-range connections in the developmental connectome during typical and
      atypical brain maturation.
AB  - The human brain is remarkably complex with connectivity constituting its basic
      organizing principle. Although long-range connectivity has been focused on in
      most research, short-range connectivity is characterized by unique and
      spatiotemporally heterogeneous dynamics from infancy to adulthood. Alterations in
      the maturational dynamics of short-range connectivity has been associated with
      neuropsychiatric disorders, such as autism and schizophrenia. Recent advances in
      neuroimaging techniques, especially diffusion magnetic resonance imaging (dMRI),
      resting-state functional MRI (rs-fMRI), electroencephalography (EEG) and
      magnetoencephalography (MEG), have made quantification of short-range
      connectivity possible in pediatric populations. This review summarizes findings
      on the development of short-range functional and structural connections at the
      macroscale. These findings suggest an inverted U-shaped pattern of maturation
      from primary to higher-order brain regions, and possible "hyper-" and "hypo-"
      short-range connections in autism and schizophrenia, respectively. The precisely
      balanced short- and long-range connections contribute to the integration and
      segregation of the connectome during development. The mechanistic relationship
      among short-range connectivity maturation, the developmental connectome and
      emerging brain functions needs further investigation, including the refinement of
      methodological approaches.

PMID- 29024683
TI  - The thermoduric effects of site-directed mutagenesis of proline and lysine on
      dextransucrase from Leuconostoc mesenteroides 0326.
AB  - Dextransucrase (DSR, EC2.4.5.1) from Leuconostoc mesenteroides 0326 which
      catalyzes sucrose to produce dextran, are popularly used in food and medicine
      industries. However, its poor kinetic stability especially at higher temperatures
      is a limiting factor for developing industrial applications. The aim of this
      study is to improve the enzyme activity and thermal stability of dextransucrase
      by single, double and triple mutations of proline and lysine. In this work, Pro
      473, Pro-678, and Pro-856 were selected as engineering targets and individually
      replaced with serine. Lys-378, Lys-725, and Lys-955 were replaced with threonine,
      respectively. Mutant P473S/P856S (MW: 170kDa) was selected as the highest
      enzymatic activity mutant from fourteen mutants. Specifically, the mutant
      P473S/P856S showed a significant increase in thermal inactivation with a 7.4-fold
      increase in half-life at 35 degrees C and a 2-fold increase in catalytic
      efficiency compared with the wild-type. The results of structural simulation are
      demonstrated that the new intramolecular hydrogen bonds in mutated enzymes
      increased structural stability, thereby increasing the thermal stability. The
      thermal stable mutants have an enormous application potential in food and
      pharmaceutical industry.

PMID- 29024682
TI  - History of concussion impacts electrophysiological correlates of working memory.
AB  - Sports-related concussions occur in approximately 21% of college athletes with
      implications for long-term cognitive impairments in working memory. Working
      memory involves the capacity to maintain short-term information and integrate
      with higher-order cognitive processing for planning and behavior execution,
      critical skills for optimal cognitive and athletic performance. This study
      quantified working memory impairments in 36 American football college athletes
      (18-23years old) using event-related potentials (ERPs). Despite performing
      similarly in a standard 2-back working memory task, athletes with history of
      concussion exhibited larger P1 and P3 amplitudes compared to Controls. Concussion
      History group latencies were slower for the P1 and faster for the N2. Source
      estimation analyses indicated that previously concussed athletes engaged
      different brain regions compared to athletes with no concussion history. These
      findings suggest that ERPs may be a sensitive and objective measure to detect
      long-term cognitive consequences of concussion.

PMID- 29024684
TI  - Duplex/quadruplex oligonucleotides: Role of the duplex domain in the
      stabilization of a new generation of highly effective anti-thrombin aptamers.
AB  - Recently, mixed duplex/quadruplex oligonucleotides have attracted great interest
      for use as biomedical aptamers. In the case of anti-thrombin aptamers, the
      addition of duplex-forming sequences to a G-quadruplex module identical or very
      similar to the best-known G-quadruplex of the Thrombin Binding Aptamer (HD1)
      results in new or improved biological properties, such as higher activity or
      different recognition properties with respect to HD1. Remarkably, this bimodular
      fold was hypothesized, based on its sequence, for the only anti-thrombin aptamer
      in advanced clinical trial, NU172. Whereas cation modulation of G-quadruplex
      conformation and stability is well characterized, only few data from similar
      analysis on duplex/quadruplex oligonucleotides exist. Here we have performed a
      characterization of structure and stability of four different duplex/quadruplex
      anti-thrombin aptamers, including NU172, in the presence of different cations and
      in physiological-mimicking conditions in comparison to HD1, by means of
      spectroscopic techniques (UV and circular dichroism) and differential scanning
      calorimetry. Our data show a strong reciprocal influence of each domain on the
      stability of the other and in particular suggest a stabilizing effect of the
      duplex region in the presence of solutions mimicking the physiological
      conditions, strengthening the idea that bimodular aptamers present better
      therapeutic potentialities than those containing a single G-quadruplex domain.

PMID- 29024685
TI  - Cardiac pathologic findings in 3 unusual cases of sudden cardiac death related to
      anorexiant drugs.
AB  - Amphetamine congeners can be prescribed as anorexiant drugs despite their
      potential adverse effects, including cardiac toxicity. However, the morphologic
      features of cardiac damage related to protracted use of these compounds are
      unknown. We provide a detailed description of cardiac autopsy findings in 3 cases
      of sudden death associated with protracted use of high doses of phendimetrazine
      and/or phenylpropanolamine or bupropion prescribed as anorexiants, in association
      with other compounds. The main cardiac findings were similar in all 3 cases: (1)
      mild-moderate hypertrophy of the left ventricle and/or the septum; (2) myocardial
      nonischemic scarring (midmural and/or subepicardial) appearing as discrete foci
      or with a bandlike morphology; (3) mild-moderate intramural small vessel disease
      in the absence of significant epicardial coronary artery stenosis; and (4)
      acute/recent inflammatory lesions consistent with toxic myocarditis. In summary,
      the detailed pathology examination of the heart in these 3 cases revealed
      myocardial lesions identical to those reported in catecholamine myocardial damage
      in all their various stages of evolution. In the presence of a clinical history
      of long-term intake of anorexiants of this category, it is most important at
      autopsy to recognize and correctly interpret the acute and chronic myocardial
      lesions of the type herein described because they represent an anatomical
      substrate for arrhythmic death.

PMID- 29024686
TI  - Increased age-adjusted hazard of death associated with a common single nucleotide
      polymorphism of the human RAD52 gene in a cardiovascular cohort.
AB  - Aging may be characterized as the progressive increase of the risk of death
      caused by a decrease of almost all bodily functions. While a great number of
      model organism studies have established the role of DNA double strand breaks
      (DSBs) as one of the main causes of aging, few studies have examined whether
      common polymorphisms in human DSB repair genes influence aging and mortality.
      More importantly, to the best of our knowledge, no longitudinal study has thus
      far examined the link between polymorphisms in DSB repair and the risk of death.
      This longitudinal study thus analyses whether four common polymorphisms
      (rs2155209, rs7963551, rs17105278, rs2735383) in four selected DSB repair genes
      (MRE11A, RAD52, RAD51B, NBS1) influence the hazard of age-adjusted death in a
      cohort of patients with typical symptoms of ischemic heart disease. The results
      have shown that rs7963551 G/T heterozygotes exhibit a significantly increased
      hazard of death when compared with the combined GG and TT homozygotes (HR=1.42,
      95% CI: 1.06-1.91, p=0.018). This study indicates that the SNP affecting
      efficiency of DSB repair may influence aging in humans.

PMID- 29024688
TI  - Vitiligo Skin: Exploring the Dermal Compartment.
AB  - There is an increasing interest in the apparently normal skin in vitiligo.
      Altered expression of the adhesion molecule E-cadherin and persistent deregulated
      intracellular redox status that promotes the acquisition of a stress-induced
      senescent phenotype in melanocytes of normally pigmented skin from patients with
      vitiligo have been described. Growing evidence has shown that such cellular and
      functional alterations are not necessarily restricted to melanocytes but may be
      extended to other cutaneous cell populations in both lesional and nonlesional
      areas. However, whether dermal fibroblasts exhibit related alterations that may
      contribute to the defects associated with melanocytes in vitiligo is not known.
      Here we reveal within the dermal compartment cells a myofibroblast phenotype and
      a predisposition to premature senescence, indicating the existence of altered
      cross-talk between dermal and epidermal components that may affect melanocyte
      functionality even in the apparently normal skin of patients with vitiligo.

PMID- 29024687
TI  - A novel mycovirus associated to Alternaria alternata comprises a distinct lineage
      in Partitiviridae.
AB  - In the present work, we report a novel mycovirus that infects Alternaria
      alternata. The mycovirus has isometric particles of approximately 30nm and the
      genome consists of two molecules of dsRNA, dsRNA1 with 1833bp, encoding a
      putative RNA-dependent RNA polymerase (RdRp) and dsRNA2, with 1680bp in length,
      encoding the putative capsid protein (CP). RdRp analysis revealed low amino acid
      identity with RdRps with species in the genus Gammapartitivirus, and the
      alignment of the RdRp revealed all the six conserved motifs present in members of
      Partitiviridae. The putative coat protein (CP) analysis revealed similarity with
      the putative CP of Botryosphaeria dothidea partitivirus 1 (BdPV1), a divergent
      partitivirus. We propose that Alternaria alternata partitivirus 1 (AtPV1) is a
      novel species and comprises a distinct lineage related to genus Gammapartitivirus
      in the family Partitiviridae, apparently on the threshold of radiation of a new
      genus, together with BdPV1. Vertical transmission tests showed that AtPV1 was
      transmitted to 100% conidial progeny and standard curing was unable to eliminate
      it from the host, characterizing it as a persistent virus. The absence of a virus
      free isogenic lineage prevented us from accessing the details of the interaction
      between AtPV1 and A. alternata. Therefore, it remains unclear whether the
      morphological plasticity observed or the inability of the A. alternata isolate
      AVi1 to cause disease in plants is associated with AtPV1 infection.

PMID- 29024689
TI  - Xeroderma Pigmentosum Diagnosis Using a Flow Cytometry-Based Nucleotide Excision
      Repair Assay.

PMID- 29024690
TI  - Sodium channel current loss of function in induced pluripotent stem cell-derived
      cardiomyocytes from a Brugada syndrome patient.
AB  - Brugada syndrome predisposes to sudden death due to disruption of normal cardiac
      ion channel function, yet our understanding of the underlying cellular mechanisms
      is incomplete. Commonly used heterologous expression models lack many
      characteristics of native cardiomyocytes and, in particular, the individual
      genetic background of a patient. Patient-specific induced pluripotent stem (iPS)
      cell-derived cardiomyocytes (iPS-CM) may uncover cellular phenotypical
      characteristics not observed in heterologous models. Our objective was to
      determine the properties of the sodium current in iPS-CM with a mutation in SCN5A
      associated with Brugada syndrome. Dermal fibroblasts from a Brugada syndrome
      patient with a mutation in SCN5A (c.1100G>A, leading to Nav1.5_p.R367H) were
      reprogrammed to iPS cells. Clones were characterized and differentiated to form
      beating clusters and sheets. Patient and control iPS-CM were structurally
      indistinguishable. Sodium current properties of patient and control iPS-CM were
      compared. These results were contrasted with those obtained in tsA201 cells
      heterologously expressing sodium channels with the same mutation. Patient-derived
      iPS-CM showed a 33.1-45.5% reduction in INa density, a shift in both activation
      and inactivation voltage-dependence curves, and faster recovery from
      inactivation. Co-expression of wild-type and mutant channels in tsA201 cells did
      not compromise channel trafficking to the membrane, but resulted in a reduction
      of 49.8% in sodium current density without affecting any other parameters.
      Cardiomyocytes derived from iPS cells from a Brugada syndrome patient with a
      mutation in SCN5A recapitulate the loss of function of sodium channel current
      associated with this syndrome; including pro-arrhythmic changes in channel
      function not detected using conventional heterologous expression systems.

PMID- 29024691
TI  - Mechanisms involved in the increased sensitivity of the rabbit basilar artery to
      atrial natriuretic peptide in diabetes.
AB  - Atrial natriuretic peptide (ANP) is a vasodilator with significant regional
      differences and controversial effects in the cerebral circulation, a vascular bed
      particularly prone to diabetes-induced complications. The present study has
      investigated how alloxan-induced diabetes modifies the mechanisms involved in the
      response of the rabbit basilar artery to ANP. ANP (10-12-10-7M) relaxed
      precontracted basilar arteries, with higher potency in diabetic than in control
      rabbits. In arteries from both groups of animals, endothelium removal reduced ANP
      induced relaxations. Inhibition of NO-synthesis attenuated ANP-induced relaxation
      but this attenuation was lower in diabetic than in control rabbits. In control
      rabbits, indomethacin displaced to the left the concentration-response curve to
      ANP, without significantly modifying the Emax value. In diabetic rabbits,
      indomethacin significantly enhanced arterial relaxations to ANP. In KCl
      depolarised arteries, relaxation to ANP was almost abolished both in control and
      in diabetic rabbits. Iberiotoxin inhibited relaxations to ANP in both groups of
      rabbits. Glibenclamide and 4-aminopyridine inhibited the ANP-induced relaxations
      more in diabetic than in control rabbits. Basilar arteries from diabetic rabbits
      showed decreased natriuretic peptide receptor C expression and no changes in
      natriuretic peptide receptor A, large conductance calcium-activated K+ channels
      (BKCa), ATP-sensitive K+ channels (KATP) and voltage-sensitive K+ channels (KV)
      expression. These results suggest that diabetes enhances the sensitivity of the
      rabbit basilar artery to ANP by mechanisms that at least include reduced
      expression of natriuretic peptide receptor C, and enhanced activity of KATP and
      KV channels. Furthermore, diabetes reduces endothelial NO and prostacyclin which
      mediate arterial relaxation to ANP.

PMID- 29024693
TI  - Multilocus sequence analysis of Echinococcus granulosus strains isolated from
      humans and animals in Iran.
AB  - Echinococcus granulosus is now considered a complex consisting of at least four
      species and ten genotypes. Different molecular targets have been described for
      molecular characterization of E. granulosus; however, in almost all studies only
      one or two of the targets have been used, and only limited data is available on
      the utilization of multiple loci. Therefore, we investigated the genetic
      diversity among 64 strains isolated from 138 cyst specimens of human and animal
      isolates, using a set of nuclear and mitochondrial genes; i.e., cytochrome c
      oxidase subunit 1 (cox1), NADH dehydrogenase subunit 1 (nad1), ATPase subunit 6
      (atp6), 12S rRNA (12S), and Actin II (act II). In comparison to the use of
      molecular reference targets (nad1 + cox1), using singular target (act II or 12S
      or atp6) yielded lower discriminatory power. Act II and 12S genes could
      accurately discriminate the G6 genotype, but they were not able to differentiate
      between G1 and G3 genotypes. As the G1 and G3 genotypes belong to the E.
      granulosus sensu stricto, low intra-species variation was observed for act II and
      12S. The atp6 gene could identify the G3 genotype but could not differentiate G6
      and G1 genotypes. Using concatenated sequence of five genes (cox1 + nad1 + atp6 +
      12S + act II), genotypes were identified accurately, and markedly higher
      resolution was obtained in comparison with the use of reference markers (nad1 +
      cox1) only. Application of multilocus sequence analysis (MLSA) to large-scale
      studies could provide valuable epidemiological data to make efficient control and
      management measures for cystic echinococcosis.

PMID- 29024692
TI  - The role of hepatocyte growth factor in corneal wound healing.
AB  - Hepatocyte growth factor (HGF) is a glycoprotein produced by mesenchymal cells
      and operates as a key molecule for tissue generation and renewal. During corneal
      injury, HGF is primarily secreted by stromal fibroblasts and promotes epithelial
      wound healing in a paracrine manner. While this mesenchymal-epithelial
      interaction is well characterized in various organs and the cornea, the role of
      HGF in corneal stromal and endothelial wound healing is understudied. In
      addition, HGF has been shown to play an anti-fibrotic role by inhibiting
      myofibroblast generation and subsequent production of a disorganized
      extracellular matrix and tissue fibrosis. Therefore, HGF represents a potential
      therapeutic tool in numerous organs in which myofibroblasts are responsible for
      tissue scarring. Corneal fibrosis can be a devastating sequela of injury and can
      result in corneal opacification and retrocorneal membrane formation leading to
      severe vision loss. In this article, we concisely review the available literature
      regarding the role of HGF in corneal wound healing. We highlight the influence of
      HGF on cellular behaviors in each corneal layer. Additionally, we suggest the
      possibility that HGF may represent a therapeutic tool for interrupting
      dysregulated corneal repair processes to improve patient outcomes.

PMID- 29024694
TI  - Cathepsin D non-proteolytically induces proliferation and migration in human
      omental microvascular endothelial cells via activation of the ERK1/2 and PI3K/AKT
      pathways.
AB  - Epithelial ovarian cancer (EOC) frequently metastasises to the omentum, a process
      that requires pro-angiogenic activation of human omental microvascular
      endothelial cells (HOMECs) by tumour-secreted factors. We have previously shown
      that ovarian cancer cells secrete a range of factors that induce pro-angiogenic
      responses e.g. migration, in HOMECs including the lysosomal protease cathepsin D
      (CathD). However, the cellular mechanism by which CathD induces these cellular
      responses is not understood. The aim of this study was to further examine the pro
      angiogenic effects of CathD in HOMECs i.e. proliferation and migration, to
      investigate whether these effects are dependent on CathD catalytic activity and
      to delineate the intracellular signalling kinases activated by CathD. We report,
      for the first time, that CathD significantly increases HOMEC proliferation and
      migration via a non-proteolytic mechanism resulting in activation of ERK1/2 and
      AKT. These data suggest that EOC cancer secreted CathD acts as an extracellular
      ligand and may play an important pro-angiogenic, and thus pro-metastatic, role by
      activating the omental microvasculature during EOC metastasis to the omentum.

PMID- 29024696
TI  - Wandering thoughts about consciousness, the brain, and the commentary system of
      Larry Weiskrantz.
AB  - Larry Weiskrantz has always pursued a keen interest in consciousness in humans
      and other animals by performing clever experiments and proposing clever ideas. In
      this rather idiosyncratic essay I selectively review some old and new evidence on
      real and apparent losses of consciousness in humans, new means that allow the
      human brain to expose its conscious awareness directly, and experiments on
      animals that may bridge their consciousness with that of humans.

PMID- 29024697
TI  - Reply to: "Direct antiviral agents and risk of HCC: Waiting for Godot".

PMID- 29024698
TI  - Pediatric CLIF-SOFA score is the best predictor of 28-day mortality in children
      with decompensated chronic liver disease.
AB  - BACKGROUND & AIMS: Early identification of children with decompensated chronic
      liver disease (DCLD) at risk of short-term mortality helps improve outcome. We
      aimed to evaluate the predictors of outcome and role of Child-Pugh, pediatric end
      stage liver disease (PELD) and pediatric chronic liver failure sequential organ
      failure assessment (pCLIF-SOFA) score for prognosticating 28-day mortality in
      children with DCLD. METHODS: DCLD children were prospectively evaluated with a
      clinico-laboratory proforma and followed for 28 days to determine outcome. Child
      Pugh, PELD and pCLIF-SOFA were calculated at admission. Univariate and
      multivariate analysis was performed to identify the best predictors of outcome.
      RESULTS: A total of 110 children (74 boys, 96 [4-204] months) were enrolled and
      37 (33.6%) died at 28 days. Significant risk factors for mortality were a higher
      international normalized ratio (hazard ratio [HR] 1.17; 95% CI 1.04-1.31; p
      <0.001) and bilirubin (HR 1.04; 95% CI 1.01-1.08; p <0.001), lower albumin (HR
      0.46; 95% CI 0.27-0.77; p = 0.03) and sodium (HR 0.93; 95% CI 0.89-0.98; p =
      0.01), absence of treatable etiology (HR 2.00; 95% CI 1.40-2.87; p = 0.001) and
      presence of organ failure (HR 3.22; 95% CI 1.98-10.58; p <0.001). Organ failure
      and serum sodium were independent predictors of poor outcome on multivariate
      analysis. pCLIF-SOFA (16 [9-22] vs. 9 [5-15]), Child-Pugh (11 [9-15] vs. 10 [8
      14]) and PELD (22.2 [7.5-45.3] vs. 15.3 [4.5-23.9]) scores were significantly
      higher in non-survivors. The area under the curve was 0.977 for pCLIF-SOFA, 0.815
      for Child-Pugh score, and 0.741 for PELD score. A pCLIF-SOFA score of >=11
      identified 28-day mortality with a sensitivity and specificity of 94.9% and
      91.5%, respectively. CONCLUSION: Thirty-four percent of children with DCLD have a
      poor short-term outcome. Organ failure and low serum sodium are independent
      predictors of outcome. pCLIF-SOFA performs better than Child-Pugh and PELD in
      prognostication of 28-day mortality. Our study supports the use of scores based
      on organ failure in prognosticating children with DCLD. LAY SUMMARY: The ability
      to predict the course of a disease is an important part of the assessment,
      enabling timely interventions that improve outcomes. We evaluated the outcome
      (death vs. survival) and compared three different scoring systems for their
      ability to predict mortality within 28 days in children with decompensated
      chronic liver disease (DCLD). One-third of children with DCLD died within 28 days
      and the pediatric chronic liver failure sequential organ failure assessment
      score, which considers the main organ systems of the body (lungs, liver, brain,
      kidney, blood and cardiac) fared better for identification of children with a
      poor outcome than the Child-Pugh and pediatric end-stage liver disease score
      which comprise of only liver-related parameters. Our study supports the use of
      scores based on organ failure in prognosticating children with DCLD.

PMID- 29024699
TI  - Direct antiviral agents and risk of HCC: Waiting for Godot.

PMID- 29024695
TI  - COPs and POPs Patrol Inflammasome Activation.
AB  - Sensing and responding to pathogens and tissue damage is a core mechanism of
      innate immune host defense, and inflammasomes represent a central cytosolic
      pattern recognition receptor pathway leading to the generation of the pro
      inflammatory cytokines interleukin-1beta and interleukin-18 and pyroptotic cell
      death that causes the subsequent release of danger signals to propagate and
      perpetuate inflammatory responses. While inflammasome activation is essential for
      host defense, deregulated inflammasome responses and excessive release of
      inflammatory cytokines and danger signals are linked to an increasing spectrum of
      inflammatory diseases. In this review, we will discuss recent developments in
      elucidating the role of PYRIN domain-only proteins (POPs) and the related CARD
      only proteins (COPs) in regulating inflammasome responses and their impact on
      inflammatory disease.

PMID- 29024700
TI  - High YBX1 expression indicates poor prognosis and promotes cell migration and
      invasion in nasopharyngeal carcinoma.
AB  - Y-box binding protein-1 (YBX1) is a multifunctional protein and often acts as an
      indicator of poor prognosis in cancers. Increasing evidence has shown that the
      levels of YBX1 protein were closely associated with multidrug resistance,
      relapse, metastasis and poor prognosis in cancers. However, its role in
      nasopharyngeal carcinoma (NPC) metastasis remains unknown. In our study, we
      discovered that the expression of YBX1 was increased in nasopharyngeal carcinoma
      tissues. YBX1 protein levels positively correlated with T stage and metastasis of
      NPC patients. Moreover, expression of YBX1 was negatively correlated with
      membrane E-cadherin levels and positively correlated with Vimentin expression. In
      vitro, the expression of YBX1 was closely related to the invasive and migratory
      ability of nasopharyngeal carcinoma cells. Knockdown of YBX1 inhibited migration
      and invasion in 5-8F cells, and over-expression of YBX1 promoted CNE1 cells
      migration and invasion. Transforming growth factor-beta1 (TGF-beta1) treatment
      led to epithelial-to-mesenchymal transition (EMT) in CNE1 cells accompanied by
      elevated YBX1 expression. On the contrary, knockdown of YBX1 partially inhibited
      the TGF-beta1-induced CNE1 cell migration, together with changes of EMT
      associated markers. Our study revealed that TGF-beta1/YBX1 signaling might be one
      of novel mechanisms mediating EMT in NPC, providing a new target for the
      treatment of nasopharyngeal carcinoma.

PMID- 29024701
TI  - Dehydroascorbic Acid and pGPMA Dual Modified pH-Sensitive Polymeric Micelles for
      Target Treatment of Liver Cancer.
AB  - In clinical therapy, the poor prognosis of hepatocellular carcinoma (HCC) is
      mainly attributed to the failure of chemotherapeutical agents to accumulate in
      tumor as well as lack of potency of tumor penetration. In this work, we developed
      actively tumor-targeting micelles with pH-sensitive linker as a novel nanocarrier
      for HCC therapy. These micelles comprised biodegradable poly(ethylene glycol)
      poly(aspartate) polymers, in which paclitaxel can be covalently conjugated to
      pAsp via an acid-labile acetal bond to form pH-responsive structures. In vitro
      drug release studies showed that these structures were stable in physiological
      condition, whereas collapsed once internalized into cells due to the mildly
      acidic environment in endo/lysosomes, resulting in facilitated intracellular
      paclitaxel release. In addition, dehydroascorbic acid and guanidinopropyl
      methacrylamide polymers were decorated on the surface of micelles to achieve
      specific tumor accumulation and tumor penetration. Cellular uptake and in vivo
      imaging studies proved that these micelles had remarkable targeting property
      toward hepatocarcinoma cells and tumor. Enhanced anti-HCC efficacy of the
      micelles was also confirmed both in vitro and in vivo. Therefore, this micellar
      system may be a potential platform of chemotherapeutics delivery for HCC therapy.

PMID- 29024702
TI  - Polycystic ovarian syndrome (PCOS): Long-term metabolic consequences.
AB  - Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women
      during their reproductive ages, associated with a plethora of cardiometabolic
      consequences, with obesity, insulin resistance and hyperandrogenemia playing a
      major role in the degree of such manifestations. These consequences include
      increased risk of glucose intolerance and diabetes mellitus (both type 2 and
      gestational), atherogenic dyslipidemia, systemic inflammation, non-alcoholic
      fatty liver disease, hypertension and coagulation disorders. Whether this cluster
      of metabolic abnormalities is also translated in increased cardiovascular disease
      (CVD) morbidity and mortality in later life, remains to be established. Data so
      far based on markers of subclinical atherosclerosis as well as retrospective and
      prospective cohort studies indicate a possible increased CVD risk, mainly for
      coronary heart disease. Future studies are needed to further elucidate this
      issue.

PMID- 29024703
TI  - Massive esophageal hemorrhage.

PMID- 29024704
TI  - EUS-guided pancreatic pseudoaneurysm therapy: better to be lucky than good.

PMID- 29024705
TI  - Management of a circumferential duodenal polyp.

PMID- 29024706
TI  - Identification of circular RNAs in human aortic valves.
AB  - With the wide application of RNA-Seq technology, thousands of circular RNAs
      (circRNAs) have been identified in different type of tissues and cells in many
      organisms, but little is known on the human aortic valve expressed circRNAs. In
      this study, we identified all circRNAs in two calcified human aortic valves, and
      characterized the features of all circRNAs. A total of 5476 circRNAs were
      identified in human aortic valves, including 1412 (25.79%) aortic valve specific
      circRNAs. Next, we showed that most aortic valve specific circRNAs were derived
      from the exonic regions of their host genes, and majority of the host genes
      contained less than three circRNAs. To predict the potential function of aortic
      valve specific circRNAs, we performed the GO (Gene Ontology) and KEGG (Kyoto
      Encyclopedia of Genes and Genomes) enrichment analysis for the host genes, and
      identified both microRNA (miRNA) and RNA binding protein (RBP) binding sites
      inside aortic valve specific circRNAs. Results showed that these host genes were
      involved in some aortic valve related function pathways, such as ECM-receptor
      interaction pathway, ErbB signaling pathway, and vascular smooth muscle
      contraction pathway. We also found that most aortic valve specific circRNAs
      harbored abundant miRNA response elements (MREs), and some aortic valve specific
      circRNAs could bind to RBP of interest. Functional analysis suggested that these
      aortic valve specific circRNAs could act as post-transcriptional regulators.

PMID- 29024707
TI  - Gene expression profiling of brain metastatic cell from triple negative breast
      cancer: Understanding the molecular events.
AB  - Brain metastatic triple negative breast cancer (BM-TNBC) is afflicted with
      unfavorable prognosis. However, the molecular events underlying BM-TNBC remain
      largely unknown. In the present study, we conducted gene expression microarray
      analysis using the triple negative breast cancer cell line MDA-MB-231 and its
      brain metastatic derivative (MDA-MB-231Brm). Results of microarray analysis
      showed that a total of 4296 genes were differentially expressed, of which 2433
      genes were up-regulated and 1863 genes were down-regulated. Gene Ontology (GO),
      KEGG pathway and protein-protein interaction (PPI) analyses indicated
      differentially expressed genes functionally categorized as genes of signal
      transduction, multicellular organismal development, ion transport, nervous system
      development, plasma membrane, extracellular region, calcium ion binding, GTP
      binding neuroactive ligand-receptor interaction. The validity of the microarray
      results was verified by quantitative real-time PCR analysis of twelve
      representative genes. The present findings revealed molecular basis and events
      associated with brain metastasis in TNBC, which will potentially contribute to
      the understanding of underlying mechanism and develop therapeutic targets.

PMID- 29024708
TI  - Nationwide Quality of Hospice Care: Findings From the Centers for Medicare &
      Medicaid Services Hospice Quality Reporting Program.
AB  - CONTEXT: With increasing use of the Medicare hospice benefit, policymakers
      recognize the need for quality measurement to assure that terminally ill patients
      receive high-quality care and have the information they need when selecting a
      hospice. Toward these goals, Centers for Medicare & Medicaid Services has been
      collecting standardized patient-level quality data via the Hospice Item Set (HIS)
      since July 1, 2014. OBJECTIVE: This article presents a first look at the national
      hospice HIS quality data. METHODS: We calculated seven quality measures using the
      HIS data. These measures are endorsed by the National Quality Forum and focus on
      important care processes hospice providers are required to perform at admission,
      including discussion of patient preferences regarding life-sustaining treatments,
      care for spiritual and existential concerns, and symptom management (pain, opioid
      induced constipation, and dyspnea). RESULTS: Our sample included 1,218,786
      hospice patients discharged from 3922 hospices from October 1, 2014 to September
      30, 2015. More than 90% of patients received screenings and assessments captured
      by six of the seven quality measures. The only exception was pain assessment, for
      which the national mean score was 78.2%. A small number of hospices (156, 4.0%)
      had perfect scores for all seven quality measures. CONCLUSIONS: Most hospices
      conduct critical assessments and discuss treatment preferences with patients at
      admission, although few hospices have perfect scores.

PMID- 29024709
TI  - Caffeine administration alters the behaviour and development of Galleria
      mellonella larvae.
AB  - The effect of feeding caffeine on the behaviour and neural proteome of Galleria
      mellonella larvae was assessed. Caffeine was administered to larvae by force
      feeding and the metabolites theobromine and theophylline were subsequently
      detected by RP-HPLC analysis. Administration of caffeine to larvae resulted in
      reduced movement and a reduction in the formation of pupae. The production of the
      muscle relaxant theophylline may contribute to the reduction in larval movement.
      Analysis of the changes in proteome of the brain and surrounding tissues of
      caffeine fed larvae revealed an increase in the abundance of immune related
      proteins such as immune-related Hdd1 (6.28 fold increase) and hemolin (1.68 fold
      increase), ATPase associated proteins such as H+ transporting ATP synthase O
      subunit isoform 1 (1.87 fold increase) and H+ transporting ATP synthase delta
      subunit (1.53 fold increase) and proteins indicative of brain trauma such as
      troponin T transcript variant B, partial (1.55 fold increase). Proteins involved
      in development and protein degradation such as SUMO-activating enzyme subunit 1
      (3.08 fold decrease) and chitin deacetylase, partial (3.67 fold decrease) were
      decreased in abundance. The results presented here indicate that caffeine is
      metabolised in a similar way in G. mellonella larvae to that in mammals and
      results in a variety of behavioural and developmental alterations. Utilisation of
      insects for studying the effects of caffeine and other neuroactive compounds may
      offer new insights into their mode of action and reduce the need to use mammals
      for this type of analysis.

PMID- 29024710
TI  - Determination of complex subclonal structures of hematological malignancies by
      multiplexed genotyping of blood progenitor colonies.
AB  - Current next-generation sequencing (NGS) technologies allow unprecedented
      insights into the mutational profiles of tumors. Recent studies in
      myeloproliferative neoplasms have further demonstrated that, not only the
      mutational profile, but also the order in which these mutations are acquired is
      relevant for our understanding of the disease. Our ability to assign mutation
      order from NGS data alone is, however, limited. Here, we present a strategy of
      highly multiplexed genotyping of burst forming unit-erythroid colonies based on
      NGS results to assess subclonal tumor structure. This allowed for the generation
      of complex clonal hierarchies and determination of order of mutation acquisition
      far more accurately than was possible from NGS data alone.

PMID- 29024711
TI  - Fluoride potentiates tubulointerstitial nephropathy caused by unilateral ureteral
      obstruction.
AB  - The contamination of ground water by fluoride has been reported worldwide. Most
      fluoride (approximately 70%) is filtered by the kidneys; humans or experimental
      animals with renal damage therefore may be more affected by fluoride exposure
      than those with normal kidney function. Tubulointerstitial fibrosis, which
      involves macrophage-promoted extracellular matrix production and myofibroblast
      migration, can be induced in rats by unilateral ureteral obstruction (UUO). We
      examined the effects of fluoride exposure on tubulointerstitial fibrosis in the
      obstructed kidney of UUO rats. The left ureters of 6-week-old male rats were
      ligated using silk sutures. Fluoride was then administered for 2 weeks at doses
      of 0, 75, and 150ppm in the drinking water. Real-time polymerase chain reaction
      was performed to analyze transforming growth factor beta 1 (TGF-beta1)
      transcription; histological and immunohistochemical staining were used to
      identify positive areas within the renal cortex and staining-positive cells by
      image analysis. Significant increases were observed in the obstructed kidneys of
      UUO rats exposed to 150ppm fluoride (compared to 0ppm) for areas or number of
      cells that stained with Masson trichrome or with antibodies against collagen type
      I, alpha-smooth muscle actin (alpha-SMA, a myofibroblast marker), ED1, ED2, and
      ED3 (macrophage markers), and TGF-beta1. Taken together, these observations
      suggested that fluoride exacerbates tuburointerstitial nephropathy resulting from
      UUO, and that this effect occurs via activation of the M2 macrophage-TGF-beta1
      fibroblast/myofibroblast-collagen synthesis pathway.

PMID- 29024712
TI  - Brief activation of GABAergic interneurons initiates the transition to ictal
      events through post-inhibitory rebound excitation.
AB  - Activation of gamma-aminobutyric acid (GABAA) receptors have been associated with
      the onset of epileptiform events. To investigate if a causal relationship exists
      between GABAA receptor activation and ictal event onset, we activated inhibitory
      GABAergic networks in the superficial layer (2/3) of the somatosensory cortex
      during hyperexcitable conditions using optogenetic techniques in mice expressing
      channelrhodopsin-2 in all GABAergic interneurons. We found that a brief 30ms
      light pulse reliably triggered either an interictal-like event (IIE) or ictal
      like ("ictal") event in the in vitro cortical 4-Aminopyridine (4-AP) slice model.
      The link between light pulse and epileptiform event onset was lost following
      blockade of GABAA receptors with bicuculline methiodide. Additionally, recording
      the chronological sequence of events following a light pulse in a variety of
      configurations (whole-cell, gramicidin-perforated patch, and multi-electrode
      array) demonstrated an initial hyperpolarization followed by post-inhibitory
      rebound spiking and a subsequent slow depolarization at the transition to
      epileptiform activity. Furthermore, the light-triggered ictal events were
      independent of the duration or intensity of the initiating light pulse,
      suggesting an underlying regenerative mechanism. Moreover, we demonstrated that
      brief GABAA receptor activation can initiate ictal events in the in vivo 4-AP
      mouse model, in another common in vitro model of epileptiform activity, and in
      neocortical tissue resected from epilepsy patients. Our findings reveal that the
      synchronous activation of GABAergic interneurons is a robust trigger for ictal
      event onset in hyperexcitable cortical networks.

PMID- 29024713
TI  - A lack of GluN2A-containing NMDA receptors confers a vulnerability to redox
      dysregulation: Consequences on parvalbumin interneurons, and their perineuronal
      nets.
AB  - The GluN2A subunit of NMDA receptors (NMDARs) plays a critical role during
      postnatal brain development as its expression increases while Glun2B expression
      decreases. Mutations and polymorphisms in GRIN2A gene, coding for GluN2A, are
      linked to developmental brain disorders such as mental retardation, epilepsy,
      schizophrenia. Published data suggest that GluN2A is involved in maturation and
      phenotypic maintenance of parvalbumin interneurons (PVIs), and these interneurons
      suffer from a deficient glutamatergic neurotransmission via GluN2A-containing
      NMDARs in schizophrenia. In the present study, we find that although PVIs and
      their associated perineuronal nets (PNNs) appear normal in anterior cingulate
      cortex of late adolescent/young adult GRIN2A KO mice, a lack of GluN2A delays PNN
      maturation. GRIN2A KO mice display a susceptibility to redox dysregulation as sub
      threshold oxidative stress and subtle alterations in antioxidant systems are
      observed in their prefrontal cortex. Consequently, an oxidative insult applied
      during early postnatal development increases oxidative stress, decreases the
      number of parvalbumin-immunoreactive cells, and weakens the PNNs in KO but not WT
      mice. These effects are long-lasting, but preventable by the antioxidant, N
      acetylcysteine. The persisting oxidative stress, deficit in PVIs and PNNs, and
      reduced local high-frequency neuronal synchrony in anterior cingulate of late
      adolescent/young adult KO mice, which have been challenged by an early-life
      oxidative insult, is accompanied with microglia activation. Altogether, these
      indicate that a lack of GluN2A-containing NMDARs alters the fine control of redox
      status, leading to a delayed maturation of PNNs, and conferring vulnerability for
      long-term oxidative stress, microglial activation, and PVI network dysfunction.

PMID- 29024714
TI  - Antibacterial effect and bond strength of a modified dental adhesive containing
      the peptide nisin.
AB  - This study attempted to incorporate the antibacterial peptide nisin into an etch
      and-rinse dental adhesive to evaluate the antibacterial activity of the modified
      adhesive against Streptococcus mutans and the bond strength. Single Bond 2 was
      used as a negative control, and nisin was incorporated at 1%, 3%, and 5% (w/v).
      The antibacterial activity against S. mutans was evaluated using the film contact
      test, the agar diffusion test, XTT assays and confocal laser scanning microscopy
      (CLSM). The microtensile bond strength (MUTBS) of the modified dental adhesive
      was also evaluated. The cured nisin-incorporated dental adhesive exhibited a
      significant inhibitory effect on the growth of S. mutans (P<0.05), and the
      inhibitory effect was strengthened as the nisin concentration increased (P<0.05).
      However, no significant differences in the agar diffusion test were found for the
      cured nisin-incorporated adhesives compared with the control group. Based on XTT
      results and CLSM images, the cured nisin-incorporated adhesive interfered with
      the adherence of S. mutans and the integrity of its biofilms (P<0.05). Compared
      with the control group, the 1% nisin group did not exhibit a significant
      difference in MUTBS (P>0.05), whereas the 3% and 5% nisin groups displayed
      decreased bond strength (P<0.05).

PMID- 29024715
TI  - Proposal of a flow scheme for the chemical-form-based quantitative analysis of
      chlorine compounds in pulp for sanitary products and verification of safety.
AB  - To determine the amounts and chemical forms of chlorine compounds in elemental
      chlorine-free (ECF) bleached pulp for sanitary products, a chemical-form-based
      quantitative analysis flow scheme was created. The scheme involves quantitative
      determination of compounds eluted in elution tests assuming dermal exposure. The
      results indicated that most of the chlorine compounds in pulp used for sanitary
      products were insoluble organically bound chlorine and water-soluble chlorides
      consisting of chloride ions. The total amount of chlorine obtained by analysis of
      the total chlorine in the pulp products was close to the sum of the amounts of
      water-soluble chlorides, residual chlorine, chloroacetic acids, and insoluble
      organically bound chlorine. Therefore, the balance of chlorine measured by the
      flow scheme was acceptable. Little residual chlorine was detected in the pulp
      products, suggesting that the chlorine dioxide used for bleaching was almost
      completely converted into inactive inorganic chlorides and organic chlorine
      compounds and that these substances do not affect the health risk posed by pulp
      products. A risk assessment of the detected chloroacetic acid and dichloroacetic
      acid revealed that there is no concern about the health risk posed by use of
      these products.

PMID- 29024716
TI  - Accelerated humoral renal allograft rejection due to HLA-C14 mediated
      allosensitization to HLA-Bw6.
AB  - OBJECTIVES: To investigate immunological mechanisms underlying accelerated
      antibody-mediated rejection (AMR) of a living-related renal allograft in a
      patient with no detectable antibodies to donor human leukocyte antigens (HLA) in
      pre-transplant sera. METHODS: Pre- and post-transplant HLA antibody specificities
      were determined by single-antigen bead assay, and crossmatching was performed by
      flow cytometry- and complement-dependent cytotoxicity-based methods. Intermediate
      and high-resolution HLA typing were performed by molecular methods. RESULTS: Pre
      transplant patient serum reacted weakly against Bw6-positive beads; cytotoxicity
      and flow crossmatches were negative. The patient was mismatched for the donor
      antigens B62 and C10 (Bw6-positive). Following transplantation, strong antibody
      responses against B62, C10, and all Bw6-positive beads were detected. This
      reactivity was initially masked by complement interference, but became apparent
      at 1:20 dilution. High-resolution typing suggested that the anti-C16 antibody
      reactivity detected was an allele-specific response to donor C*16:01 (Bw6
      positive) but not recipient C*16:02 (Bw6-negative). Alloimmunization likely
      occurred during pregnancy, during which HLA-C14 (Bw6-positive) was the only
      mismatched paternal HLA Class I allele. CONCLUSIONS: Sensitization to HLA-Bw6 via
      exposure to paternal HLA-C14 during pregnancy likely predisposed this patient to
      AMR. The case demonstrates the immunogenicity of HLA-C14-associated Bw6 epitopes
      in vivo and the clinical significance of low-level antibodies to HLA-Bw6.

PMID- 29024717
TI  - Supplementation of American ginseng berry extract mitigated cisplatin-evoked
      nephrotoxicity by suppressing ROS-mediated activation of MAPK and NF-kappaB
      signaling pathways.
AB  - Nephrotoxicity induced by cisplatin in 30% of all cisplatin treated patients
      seriously limits its clinical implication as a widely used anticancer agent, and
      may even cause patients to alter or give up cisplatin therapy. The purpose of
      this study is to test a protective effect of American ginseng berry extract
      (AGBE) on cisplatin-induced nephrotoxicity in mice. In this study, the
      histopathological changes and elevated levels of serum creatinine (CRE) and urea
      nitrogen (BUN) caused by cisplatin were significantly diminished by AGBE
      treatment. Oxidative stress caused by cisplatin, evidenced by increases in kidney
      tissues malondialdehyde (MDA) content, cytochrome P450 E1 (CYP2E1), renal 4
      hydroxynonenal (4-HNE) levels and decreases of glutathione (GSH) and superoxide
      dismutase (SOD) contents, was significantly ameliorated by AGBE pretreatment. The
      expression levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta
      (IL-1beta), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS)
      were inhibited by AGBE treatment, suggesting a suppression of inflammatory
      response. Additionally, AGBE clearly inhibited cisplatin-induced activations of
      nuclear factor-kappa B (NF-kappaB) and mitogen activated protein kinase (MAPK)
      signal pathways. Supplementation of cisplatin-intoxicated mice with AGBE also
      significantly reduced apoptotic protein levels of Bax, cleaved caspase-3,
      cytochrome c and increased anti-apoptotic protein Bcl-2. These findings highlight
      nephroprotective effect of AGBE against cisplatin-evoked nephrotoxicity through
      ROS-mediated MAPK and NF-kappaB signaling pathways.

PMID- 29024718
TI  - A Randomized Controlled Trial of Continuous Subpleural Bupivacaine After
      Thoracoscopic Surgery.
AB  - We sought to evaluate the merit of routine placement of a subpleural tunneled
      pain catheter delivering local anesthetic as measured by narcotic medication
      usage and subjective pain score analysis. Eighty-six patients were randomized
      into the subpleural catheter or intraoperative incision site injection groups in
      a 1:1 fashion, and underwent thoracoscopic surgery using 2 incisions. All
      patients had standardized anesthetic delivery and postoperative pain control.
      Patients' use of pain medication and pain scores was tracked for 7 days
      postoperatively. There was no significant difference in the 2 groups' usage of
      narcotics (P = 0.23), acetaminophen (P = 0.23), or nonsteroidal antiinflammatory
      drugs (P = 0.57) over time from linear mixed model analysis. The subpleural
      catheter group had significantly higher nonsteroidal antiinflammatory drug self
      reported usage on postoperative day 4 (P = 0.04), postoperative day 5 (P = 0.05),
      postoperative day 6 (P = 0.01), and postoperative day 7 (P <0.01). There were no
      significant differences in average daily pain scores (all P >= 0.06). Length of
      hospital stay and results from 30-day postoperative surveys were not
      significantly different between the subpleural catheter and the intraoperative
      incision site injection groups. Our results did not show any objective
      differences between the subpleural catheter and the intraoperative incision site
      injection groups to justify routine use of tunneled subpleural catheters. The
      main limitation of this study is missing self-reported data. The differences
      noted in daily nonsteroidal antiinflammatory drug use in the pain catheter arm
      may actually suggest slightly worse pain control in those patients, although the
      clinical significance seems to be minimal.

PMID- 29024719
TI  - Calcification or Not. This Is the Question. A 1-Year Study of Bovine Pericardial
      Vascular Patches (CardioCel) in Minipigs.
AB  - A main problem with bioprosthesis used for surgical correction of congenital
      cardiac malformation is its tendency to shrink and to calcify. Recently, a new
      material, that is, decellularized bovine pericardium (CardioCel), was introduced
      in clinics. It was proposed that this new patch material should not calcify and
      should be particularly suitable for the correction of vascular defects in inborn
      cardiac diseases. The aim of our chronic minipig study was to evaluate the
      performance of CardioCel patches implanted in aortic and pulmonary artery
      position, respectively. Ten minipigs aged 3 months were operated on. A CardioCel
      patch was implanted in the aorta ascendens and arteria pulmonalis, respectively.
      Seven minipigs completed the 12 months' follow-up. Angiography of both vessels,
      measurement of pressure gradients, and histologic evaluation of the implanted
      patches were carried out. Angiography of both great vessels revealed a good
      clinical outcome without stenosis. However, histologic examination of the patches
      showed calcification and neo-formation of hyaline cartilage in both vessel types.
      Staining of collagen and elastic fibers as well as alpha-smooth muscle actin
      demonstrated that the patches did not remodel into an anatomic vascular structure
      during the 1 year of implantation. In our chronic piglet model, CardioCel
      patches, when implanted in the ascending aorta and the pulmonary artery, led to
      calcification and neo-formation of hyaline cartilage in both vessel types 1 year
      after implantation. The present study indicates that the ideal patch biomaterial
      for repair of inborn cardiac diseases is still a goal not achieved yet.

PMID- 29024721
TI  - Systems approaches for identifying disease genes and drug targets.

PMID- 29024720
TI  - Disruptions to the cerebellar GABAergic system in juvenile guinea pigs following
      preterm birth.
AB  - BACKGROUND: Children that are born preterm are at an increased risk of developing
      cognitive problems and behavioural disorders, such as attention deficit
      hyperactivity disorder (ADHD). There is increasing interest in the role of the
      cerebellum in these processes and the potential involvement of GABAergic pathways
      in neurodevelopmental disorders. We propose that preterm birth, and the
      associated loss of the trophic intrauterine environment, alters the development
      of the cerebellum, contributing to ongoing neurobehavioral disorders. METHODS:
      Guinea pigs were delivered preterm (GA62) or spontaneously at term (GA69), and
      tissues collected at corrected postnatal day (PND) 28. Neurodevelopmental and
      GABAergic markers myelin basic protein (MBP), neuronal nuclei (NeuN), calbindin
      (Purkinje cells), and GAD67 (GABA synthesis enzyme) were analysed in cerebellar
      lobules IX and X by immunohistochemistry. Protein expression of GAD67 and GAT1
      (GABA transporter enzyme) were quantified by western blot, whilst neurosteroid
      sensitive GABAA receptor subunits were measured by RT-PCR. RESULTS: MBP
      immunostaining was increased in lobule IX of preterm males, and reduced in lobule
      X of preterm females when compared to their term counterparts. GAD67 staining was
      decreased in lobule IX and X of the preterm males, but only in lobule X of the
      preterm females compared to term cohorts for each sex. Internal granule cell
      layer width of lobule X was decreased in preterm cohorts of both sexes compared
      to terms. There were no differences between gestational age groups for NeuN
      staining, GAD67 and GAT1 protein expression as measured by western blotting, or
      GABAA receptor subunits as measured by RT-PCR between preterm and term for either
      sex. CONCLUSIONS: The present findings suggest that components of the cerebellar
      GABAergic system of the ex-preterm cerebellum are disrupted. The higher
      expression of myelin in the preterm males may be due to a deficit in axonal
      pruning, whereas females have a deficit in myelination at 28 corrected days of
      age. Together these ongoing alterations may contribute to the neurodevelopmental
      and behavioural disorders observed in those born preterm.

PMID- 29024722
TI  - Cellular immune activation in Sardinian middle-aged, older adults and
      centenarians.
AB  - In addition to viral infections, malignant disorders, autoimmune diseases, and
      allograft rejection episodes, neopterin increases in older people where it is
      found to be predictive of overall mortality. Thus, the serum concentrations of
      this biomarker of systemic immune and inflammation activation, were measured in a
      small cohort of Sardinian middle-aged, older adults and centenarians. There was a
      significant positive correlation between neopterin concentrations and age with
      the subjects in the 95-year-old group with the highest values. Notably, the group
      of centenarians had neopterin values comparable to those of 80- and 90-year-old
      groups, and significantly lower than that of 95-year-old group. This suggests a
      decreased monocyte/macrophage-mediated immune activation and an apparently
      preserved immune status in centenarians.

PMID- 29024723
TI  - Homocysteine concentrations in the cognitive progression of Alzheimer's disease.
AB  - OBJECTIVES: Hyperhomocysteinemia in Alzheimer's disease (AD) is widely reported
      and appears to worsen as the disease progresses. While active dietary
      intervention with vitamins B12 and folate decreases homocysteine blood levels,
      with promising clinical outcomes in Mild Cognitive Impairment (MCI), this so far
      has not been replicated in established AD populations. The aim of the study is to
      explore the relationship between hyperhomocystenemia and relevant vitamins as the
      disease progresses. METHODS: In this longitudinal cohort study, 38 participants
      with mild to moderate AD were followed for an average period of 13months. Plasma
      folate, vitamin B12 and homocysteine concentrations were measured at baseline and
      at follow-up. Dietary intake of B vitamins was also measured. Spearman's
      correlations were conducted by homocysteine and B vitamin status. RESULTS: As
      expected, cognitive status significantly declined over the follow-up period and
      this was paralleled by a significant increase in homocysteine concentrations
      (p=0.006). However, during this follow-up period there was no significant decline
      in neither dietary intake, nor the corresponding blood concentrations of vitamin
      B12/folate, with both remaining within normal values. Changes in blood
      concentrations of B vitamins were not associated with changes in homocysteine
      levels (p>0.05). CONCLUSION: In this study, the increase in homocysteine observed
      in AD patients as the disease progresses cannot be solely explained by dietary
      and blood levels of folate and vitamin B12. Other dietary and non-dietary factors
      may contribute to hyperhomocysteinemia and its toxic effect in AD, which needs to
      be explored to optimise timely intervention strategies.

PMID- 29024724
TI  - PAXgene fixation enables comprehensive metabolomic and proteomic analyses of
      tissue specimens by MALDI MSI.
AB  - An alcohol-based non-crosslinking tissue fixative, PAXgene Tissue System, has
      been proposed as alternative fixation method to formalin, providing superior and
      morphological preservation. To date, metabolites have not been assessed in
      PAXgene-fixed tissues. The study focuses on a comparison between PAXgene and
      standard formalin fixation for metabolomic analysis by MALDI mass spectrometry
      imaging. Therefore, fifty-six samples from seven mice organs were fixed with
      PAXgene (PFPE) or formalin (FFPE), embedded in paraffin, and processed to a
      tissue microarray. PAXgene was able to spatially preserve metabolites in organs
      achieving an overlap of common metabolites ranging from 34 to 78% with FFPE.
      Highly similar signal intensities and visualization of molecules demonstrated
      negligible differences for metabolite imaging on PFPE compared to FFPE tissues.
      In addition, we performed proteomic analysis of intact proteins and peptides
      derived from enzymatic digestion. An overlap of 33 to 58% was found between FFPE
      and PFPE tissue samples in peptide analysis with a higher number of PFPE-specific
      peaks. Analysis of intact proteins achieved an overlap in the range of 0 to 28%
      owing to the poor detectability of cross-linked proteins in formalin-fixed
      tissues. Furthermore, metabolite and peptide profiles obtained from PFPE tissues
      were able to correctly classify organs independent of the fixation method,
      whereas a distinction of organs by protein profiles was only achieved by PAXgene
      fixation. Finally, we applied MALDI MSI to human biopsies by sequentially
      analyzing metabolites and peptides within the same tissue section. Concerning
      prospective studies, PAXgene can be used as an alternative fixative for multi
      omic tissue analysis.

PMID- 29024725
TI  - Glucagon, a key factor in the pathophysiology of type 2 diabetes.
AB  - Excessive circulating glucagon levels have been reported in all forms of
      diabetes, clinical or experimental. The hyperglucagonemia of diabetes results
      from an excessive secretion of the hormone secondary from a deficit in insulin
      secretion and/or a dysfunction of various cells within the islets of Langerhans
      (somatostatin) leading to the notion of "paracrinopathy". Hyperglucagonemia
      contributes to the fasting and postprandial hyperglycemia in diabetic patients
      through an increased hepatic glucose production (mainly gluconeogenesis). The aim
      of the present review is to summarize the clinical and experimental arguments
      suggesting that glucagon is essential for the development of glucose
      dysregulation in diabetes.

PMID- 29024726
TI  - The antiepileptic drug levetiracetam promotes neuroblast differentiation and
      expression of superoxide dismutase in the mouse hippocampal dentate gyrus via
      PI3K/Akt signalling.
AB  - Levetiracetam (LEV), a second-generation antiepileptic drug, is commonly
      prescribed to treat certain types of seizures. Few studies have investigated the
      effects of LEV on hippocampal neurogenesis and its related mechanisms. In the
      present study, we investigated the effects of LEV on cell proliferation and
      neuronal differentiation in the mouse hippocampal dentate gyrus (DG). We here
      demonstrate a dose-dependent increase in Ki-67-immunoreactive cells in the
      subgranular zone of the DG in LEV-treated mice, and doublecortin-immunoreactive
      cells were also significantly increased in the hippocampal DG of mice treated
      with LEV. The above results indicate that LEV could improve cell proliferation
      and neuroblast differentiation in the hippocampus. In addition, we also found
      that LEV treatment improved superoxide dismutase (SOD)2, catalase and Gpx-1
      levels and increased phosphatidylinositol 3-kinase (PI3K) and phosphorylated Akt
      protein levels in the hippocampus. Further investigation of the molecular
      mechanisms underlying these effects revealed that PC12 cell was blocked by a
      pharmacological inhibitor of PI3K (LY294002), and that LEV treatment rapidly
      activated PI3K/Akt and SOD2, catalase and Gpx-1. In brief, our results indicate
      that LEV enhanced cell proliferation and neuroblast differentiation by increasing
      the expression of antioxidants and PI3K and the level of phosphorylated Akt in
      the mouse hippocampus.

PMID- 29024727
TI  - Interspecific comparison of mushroom body synaptic complexes of dimorphic workers
      in the ant genus Pheidole.
AB  - Social insects may have morphologically and behaviorally specialized workers that
      vary in requirements for sensory information processing, making them excellent
      systems to examine the relationship between brain structure and behavior. The
      density and size of synaptic complexes (microglomeruli, MG) in the mushroom
      bodies (MB) have served as proxies for processing ability and synaptic
      plasticity, and have been shown to vary among insect species that differ in
      behavioral complexity. To understand the relationship between behavioral
      specialization and synaptic structure, we examined age-related changes in MG
      density and size between minor worker and soldier subcastes in two species of
      Pheidole ants, P. dentata and P. morrisi, that differ in behavior. We
      hypothesized that task-diverse minor workers would have more densely packed MG
      than soldiers, and that species-specific differences in soldier repertories would
      be reflected in MG structure. We also examined MG variation in young and mature
      minor workers and soldiers, predicting that as workers age and develop
      behaviorally, MG would decrease in density in both subcastes due to synaptic
      pruning. Results support the hypothesis that MG density in the lip (olfactory)
      and collar (visual) regions of the MBs decrease with age in association with
      increases in bouton size in the lip. However, minors had significantly lower
      densities of MG in the lip than soldiers, suggesting MG may not show structural
      variation according to subcaste-related differences in cognitive demands in
      either species.

PMID- 29024728
TI  - Tablet coating by injection molding technology - Optimization of coating
      formulation attributes and coating process parameters.
AB  - We developed and evaluated a solvent-free injection molding (IM) coating
      technology that could be suitable for continuous manufacturing via incorporation
      with IM tableting. Coating formulations (coating polymers and plasticizers) were
      prepared using hot-melt extrusion and screened via stress-strain analysis
      employing a universal testing machine. Selected coating formulations were studied
      for their melt flow characteristics. Tablets were coated using a vertical
      injection molding unit. Process parameters like softening temperature, injection
      pressure, and cooling temperature played a very important role in IM coating
      processing. IM coating employing polyethylene oxide (PEO) based formulations
      required sufficient room humidity (>30% RH) to avoid immediate cracks, whereas
      other formulations were insensitive to the room humidity. Tested formulations
      based on Eudrajit E PO and Kollicoat IR had unsuitable mechanical properties.
      Three coating formulations based on hydroxypropyl pea starch, PEO 1,000,000 and
      Opadry had favorable mechanical (<700MPa Young's modulus, >35% elongation,
      >95*104J/m3 toughness) and melt flow (>0.4g/min) characteristics, that rendered
      acceptable IM coats. These three formulations increased the dissolution time by
      10, 15 and 35min, respectively (75% drug release), compared to the uncoated
      tablets (15min). Coated tablets stored in several environmental conditions
      remained stable to cracking for the evaluated 8-week time period.

PMID- 29024729
TI  - Integrating genome-wide association study and expression quantitative trait locus
      study identifies multiple genes and gene sets associated with schizophrenia.
AB  - Schizophrenia is a serious mental disease with high heritability. To better
      understand the genetic basis of schizophrenia, we conducted a large scale
      integrative analysis of genome-wide association study (GWAS) and expression
      quantitative trait loci (eQTLs) data. GWAS summary data was derived from a
      published GWAS of schizophrenia, containing 9394 schizophrenia patients and
      12,462 healthy controls. The eQTLs dataset was obtained from an eQTLs meta
      analysis of 5311 subjects, containing 923,021 cis-eQTLs for 14,329 genes and 4732
      trans-eQTLs for 2612 genes. Genome-wide single gene expression association
      analysis was conducted by SMR software. The SMR analysis results were further
      subjected to gene set enrichment analysis (GSEA) to identify schizophrenia
      associated gene sets. SMR detected 49 genes significantly associated with
      schizophrenia. The top five significant genes were CRELD2 (p value=1.65*10-11),
      DIP2B (p value=3.94*10-11), ZDHHC18 (p value=1.52*10-10) and ZDHHC5 (p
      value=7.45*10-10), C11ORF75 (p value=3.70*10-9). GSEA identified 80 gene sets
      with p values <0.01. The top five significant gene sets were COWLING_MYCN_TARGETS
      (p value <0.001) and CHR16P11 (p value <0.001), ACTACCT_MIR196A_MIR196B (p
      value=0.002), CELLULAR_COMPONENT_DISASSEMBLY (p value=0.002) and
      GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN (p value=0.002). Our results provide
      useful information for revealing the genetic basis of schizophrenia.

PMID- 29024731
TI  - The "Y" technique: An attempt to standardize nail dressing.

PMID- 29024730
TI  - Effects of therapeutic hypothermia on the gut microbiota and metabolome of
      infants suffering hypoxic-ischemic encephalopathy at birth.
AB  - Neonatal hypoxic ischemic encephalopathy (HIE) in the perinatal period can lead
      to significant neurological deficits in later life. Total body cooling (TBC) is a
      neuroprotective strategy used in the treatment of HIE and has been shown to
      reduce seizures and improve neurodevelopmental outcomes in treated infants.
      Little is known, however, about the effects of HIE/TBC on the developing gut
      microbiota composition and subsequent metabolic profile. Ten term infants with
      HIE who received TBC at 33.5 degrees C for 72h were recruited. A control group
      consisted of nine healthy full term infants. Faecal samples were collected from
      both groups at 2 years of age and stored at -20 degrees C. 16S rRNA amplicon
      Illumina sequencing was carried out to determine gut microbiota composition and
      1H NMR analysis was performed to determine the metabolic profile of faecal water.
      The gut microbiota composition of the HIE/TBC infants were found to have
      significantly lower proportions of Bacteroides compared to the non-cooled healthy
      control group. Alpha diversity measures detected significantly lower diversity in
      microbial richness in the HIE/TBC infant group compared to the control infants
      (Shannon index, <0.05). High inter-individual variation was found in gut
      microbiota composition and metabolic profile of both groups. Initial principal
      coordinate analysis and hierarchal clustering of compounds on MetaboAnalyst 3.0
      indicated no clear separation in the metabolic profile of these two infant
      groups. These results suggest that there is no significant impact on the gut
      microbial development of HIE/TBC infants compared to healthy infants at 2years of
      life. To our knowledge this is the first study to report the gut microbiota
      composition and metabolic profile of infants who have experienced HIE/TBC at
      birth.

PMID- 29024732
TI  - Trends in US dermatology residency and fellowship programs and positions, 2006 to
      2016.

PMID- 29024733
TI  - The tenting technique: A novel filler technique in the danger zones.

PMID- 29024735
TI  - Quantitative Analysis of Technological Innovation in Urology.
AB  - OBJECTIVE: To assess major areas of technological innovation in urology in the
      last 20 years using patent and publication data. METHODS: Patent and MEDLINE
      databases were searched between 1980 and 2012 electronically using the terms
      urology OR urological OR urologist AND "surgeon" OR "surgical" OR "surgery". The
      patent codes obtained were grouped in technology clusters, further analyzed with
      individual searches, and growth curves were plotted. Growth rates and patterns
      were analyzed, and patents were correlated with publications as a measure of
      scientific support and of clinical adoption. RESULTS: The initial search revealed
      417 patents and 20,314 publications. The top 5 technology clusters in descending
      order were surgical instruments including urinary catheters, minimally invasive
      surgery (MIS), lasers, robotic surgery, and image guidance. MIS and robotic
      surgery were the most emergent clusters in the last 5 years. Publication and
      patent growth rates were closely correlated (Pearson coefficient 0.78, P <.01),
      but publication growth rate remained constantly higher than patent growth,
      suggesting validated scientific support for urologic innovation and adoption into
      clinical practice. CONCLUSION: Patent metrics identify emergent technological
      innovations and such trends are valuable to understand progress in the field of
      urology. New surgical technologies like robotic surgery and MIS showed
      exponential growth in the last decade with good scientific vigilance.

PMID- 29024734
TI  - Clinical and dermoscopic characterization of pediatric and adolescent melanomas:
      Multicenter study of 52 cases.
AB  - BACKGROUND: Knowledge regarding the morphologic spectrum of pediatric melanoma
      (PM) is sparse, and this may in part contribute to delay in detection and thicker
      tumors. OBJECTIVE: To analyze the clinicodermoscopic characteristics of PM.
      METHODS: Retrospective study of 52 melanomas diagnosed in patients before the age
      of 20 years. RESULTS: On the basis of its clinical, dermoscopic, and
      histopathologic characteristics, PM can be classified as spitzoid or nonspitzoid.
      The nonspitzoid melanomas (n = 37 [72.3%]) presented in patients with a mean age
      of 16.3 years (range, 8-20) and were associated with a high-risk phenotype and a
      pre-existing nevus (62.2%). The spitzoid melanomas (n = 15 [27.7%]) were
      diagnosed in patients at a mean age of 12.5 years (range, 2-19) and were mostly
      de novo lesions (73.3%) located on the limbs (73.3%). Whereas less than 25% of
      PMs fulfilled the modified clinical ABCD criteria (amelanotic, bleeding bump,
      color uniformity, de novo at any diameter), 40% of spitzoid melanomas did.
      Dermoscopic melanoma criteria were found in all cases. Nonspitzoid melanomas
      tended to be multicomponent (58.3%) or have nevus-like (25%) dermoscopic
      patterns. Spitzoid melanomas revealed atypical vascular patterns with shiny white
      lines (46.2%) or an atypical pigmented spitzoid pattern (30.8%). There was good
      correlation between spitzoid subtype histopathologically and dermoscopically
      (kappa = 0.66). LIMITATIONS: A retrospective study without re-review of
      pathologic findings. CONCLUSION: Dermoscopy in addition to conventional and
      modified clinical ABCD criteria helps in detecting PM. Dermoscopy assists in
      differentiating spitzoid from nonspitzoid melanomas.

PMID- 29024736
TI  - A Survey Regarding Preference in the Management of Bilateral Stone Disease and a
      Comparison of Clavien Complication Rates in Bilateral vs Unilateral Percutaneous
      Nephrolithotomy.
AB  - OBJECTIVE: To discuss complications of simultaneous bilateral percutaneous
      nephrolithotomy (SB-PCNL) when compared with unilateral percutaneous
      nephrolithotomy and survey surgeon preference in bilateral stone disease
      management. PATIENTS AND METHODS: A database of all participating percutaneous
      nephrolithotomy (PCNL) patients who underwent treatment at Indiana University
      Health Methodist Hospital within a 10-year period from 2006 to 2015 by a single
      surgeon (JL) was utilized. Perioperative data, as well as complications, defined
      according to the Clavien grading system, were recorded. A survey of members of
      the Endourological Society was performed regarding surgical management in the
      setting of bilateral stone disease. RESULTS: A total of 563 patients were
      identified over the study period with 129 undergoing SB-PCNL. Overall, SB-PCNL
      patients had a longer procedure (176.9 vs 115.6 minutes, P <.0001), were more
      likely to undergo a secondary procedure (73% vs 44, P <.001), and had a longer
      hospital stay (3.2 vs 2.3 days, P <.001). Notably, there were no differences in
      the number or the severity of complications between the 2 groups. A total of 153
      endourologists completed the survey. Of these endourologists, 58 (38%) performed
      bilateral PCNL under anesthesia. The top reasons for electing not to perform
      bilateral PCNLs included the duration of bilateral procedures (53%), bilateral
      renal injury (48%), and rare performance of bilateral surgery (35%). CONCLUSION:
      Although the procedure length was longer in the SB-PCNL group, there were similar
      rates of complications and severity between unilateral PCNL and SB-PCNL. A
      majority of endourologists surveyed do not perform bilateral PCNL but would
      perform bilateral ureteroscopy with the duration of the procedure and concern for
      bilateral renal injury representing the most common reasons.

PMID- 29024737
TI  - Pseudomyxoma Peritonei Arising From Urachal Mucinous Adenocarcinoma.
AB  - Pseudomyxoma peritonei is a rare clinical condition that can arise from various
      primary tumors with different biological behaviors. An intraperitoneal spread of
      mucus is the characteristic of the disease. Here, we provide images from a rare
      entity, a pseudomyxoma peritonei arising from urachal mucinous adenocarcinoma. If
      clinical suspicion is high, the preoperative imaging could be almost
      pathognomonic of the disease.

PMID- 29024738
TI  - New Hybrid Mini-laparoendoscopic Single-site Partial Nephrectomy With Early
      Unclamped Technique for Renal Tumors With Intermediate PADUA Score (IDEAL Phase
      2a).
AB  - OBJECTIVE: To evaluate a new hybrid technique, which we defined as mini
      laparoendoscopic single-site partial nephrectomy (MILESS-PN), for renal masses
      presenting an intermediate PADUA score. MATERIALS AND METHODS: Forty consecutive
      cases of MILESS-PN performed between April 2013 and November 2015 were included
      in this study. Mini-laparoendoscopic single-site surgery consisted of the
      simultaneous use of two 3-mm pararectal trocars and an umbilical SILS trocar; the
      sequence of steps of MILESS-PN was comparable with standard laparoscopic partial
      nephrectomy. Demographic data and the main perioperative and oncological outcome
      parameters were gathered and analyzed. RESULTS: The median operative time was
      134.6 (interquartile range [IQR] 110-180) minutes with a median warm ischemia
      time of 12.1 (IQR 9.5-15.5) minutes. Postoperatively, 4 early complications were
      recorded and the median hospital stay was 4.2 (IQR 3.5-6.0) days. The median
      renal tumor size was 3.6 (IQR 2.4-5.3) cm with a median PADUA score of 8.3 (IQR 8
      9). The definitive pathologic results revealed a renal cell carcinoma in 32 cases
      (80%), an angiomyolipoma in 3 cases (7.5%), and an oncocytoma in 5 cases (12.5%).
      All tumors were removed with negative surgical margins, and at the median follow
      up of 34.5 (IQR 24-48) months, all patients were alive without evidence of tumor
      recurrence or port-site metastasis. A statistically significant decrease in the
      estimated glomerular filtration rate (eGFR) was observed postoperatively
      (postoperative vs preoperative median eGFR: 87.6 [IQR 70.4-101.8] and 104.7 [IQR
      82.7-123.3], P <.0001) and at 6 months (6 months vs preoperative eGFR 93.6 [IQR
      79.1-110.2] and 104.7 [IQR 82.7-123.3], P <.0001). CONCLUSION: MILESS-PN for
      renal tumors with an intermediate PADUA score in well-selected patients is not
      associated with increased risks for the patients, presenting excellent
      oncological and functional results at the midterm follow-up. Mini
      laparoendoscopic single-site surgery could represent a valid alternative to
      laparoendoscopic single-site surgery or minilaparoscopy because of its higher
      surgical reproducibility.

PMID- 29024739
TI  - Direct antiviral agents (DAAs) - A new age in the treatment of hepatitis C virus
      infection.
AB  - Hepatitis C virus (HCV) is a global health problem, because infection frequently
      leads to chronic hepatitis C eventually progressing to liver cirrhosis and liver
      cancer. Improved insights into the HCV replication cycle and the role of HCV non
      structural proteins have recently enabled to identify drugs directly acting on
      specific HCV target structures. Agents from three drug classes have been
      developed and approved by the health authorities. Combinations of two or more
      drugs from different classes achieve high (>90%) HCV clearance rates and are well
      tolerated. This interferon-free DAA (direct antiviral agent) therapy has
      revolutionized antiviral therapy in hepatitis C so that successful hepatitis C
      treatment can be offered to virtually all patients irrespective of their co
      morbidity. This review provides an overview over currently approved regimens and
      outlines their use in clinical practice. In addition potential short-comings of
      the current therapeutic options such as drug-drug interactions and selection of
      viral resistance are addressed. DAA combination therapy has the potential to
      obtain global control over hepatitis C. However, easy access to DAAs,
      availability of reliable HCV diagnostics, and affordable costs remain still
      important goals, which must be reached to globally eliminate hepatitis C.

PMID- 29024740
TI  - Antimicrobial peptides, nanotechnology, and natural metabolites as novel
      approaches for cancer treatment.
AB  - Despite the advances in tumor identification and treatment, cancer remains the
      primary driver of death around the world. Also, regular treatments for the
      disease are incapable of targeting particular cancer types at different stages
      since they are not specifically focused on harmful cells since they influence
      both solid and tumor cells, causing side effects and undesirable symptoms.
      Therefore, novel strategies should be developed to treat this disease. Several
      efforts have been made in this direction to find more effective alternatives to
      cancer treatment, such as the use of antimicrobial peptides (AMPs) with
      antitumoral activity, nanocarriers and natural compounds from a variety of
      sources. AMPs are more specific to their targets because of electrostatic
      interaction between AMPs and the cancer cells' plasma membrane. Nanocarriers may
      be used for the delivery of non-soluble drugs, which are poorly stable or require
      a controlled release. In addition, natural compounds have been a rich source of
      anti-cancer agents for decades. In this review, these three approaches will be
      discussed, showing recent advances and advantages of using these strategies to
      treat cancer as well as the combination of these approaches increasing anticancer
      activity.

PMID- 29024741
TI  - In vivo potency revisited - Keep the target in sight.
AB  - Potency is a central parameter in pharmacological and biochemical sciences, as
      well as in drug discovery and development endeavors. It is however typically
      defined in terms only of ligand to target binding affinity also in in vivo
      experimentation, thus in a manner analogous to in in vitro studies. As in vivo
      potency is in fact a conglomerate of events involving ligand, target, and target
      ligand complex processes, overlooking some of the fundamental differences between
      in vivo and in vitro may result in serious mispredictions of in vivo efficacious
      dose and exposure. The analysis presented in this paper compares potency measures
      derived from three model situations. Model A represents the closed in vitro
      system, defining target binding of a ligand when total target and ligand
      concentrations remain static and constant. Model B describes an open in vivo
      system with ligand input and clearance (Cl(L)), adding in parallel to the
      turnover (ksyn, kdeg) of the target. Model C further adds to the open in vivo
      system in Model B also the elimination of the target-ligand complex (ke(RL)) via
      a first-order process. We formulate corresponding equations of the equilibrium
      (steady-state) relationships between target and ligand, and complex and ligand
      for each of the three model systems and graphically illustrate the resulting
      simulations. These equilibrium relationships demonstrate the relative impact of
      target and target-ligand complex turnover, and are easier to interpret than the
      more commonly used ligand-, target- and complex concentration-time courses. A new
      potency expression, labeled L50, is then derived. L50 is the ligand concentration
      at half-maximal target and complex concentrations and is an amalgamation of
      target turnover, target-ligand binding and complex elimination parameters
      estimated from concentration-time data. L50 is then compared to the dissociation
      constant Kd (target-ligand binding affinity), the conventional Black & Leff
      potency estimate EC50, and the derived Michaelis-Menten parameter Km (target
      ligand binding and complex removal) across a set of literature data. It is
      evident from a comparison between parameters derived from in vitro vs. in vivo
      experiments that L50 can be either numerically greater or smaller than the Kd (or
      Km) parameter, primarily depending on the ratio of kdeg-to-ke(RL). Contrasting
      the limit values of target R and target-ligand complex RL for ligand
      concentrations approaching infinity demonstrates that the outcome of the three
      models differs to a great extent. Based on the analysis we propose that a better
      understanding of in vivo pharmacological potency requires simultaneous assessment
      of the impact of its underlying determinants in the open system setting. We
      propose that L50 will be a useful parameter guiding predictions of the effective
      concentration range, for translational purposes, and assessment of in vivo target
      occupancy/suppression by ligand, since it also encompasses target turnover - in
      turn also subject to influence by pathophysiology and drug treatment. Different
      compounds may have similar binding affinity for a target in vitro (same Kd), but
      vastly different potencies in vivo. L50 points to what parameters need to be
      taken into account, and particularly that closed-system (in vitro) parameters
      should not be first choice when ranking compounds in vivo (open system).

PMID- 29024742
TI  - CYP-mediated drug metabolism in the brain impacts drug response.
AB  - The functional role of cytochrome P450 (CYP) enzymes in the brain is an exciting
      and evolving field of research. CYPs are present and active in the brain, with
      heterogeneous patterns of expression, activity, and sensitivity to modulation
      across cell types, regions, and species. Despite total brain CYP expression being
      a fraction of hepatic CYP expression, the expanding literature of in vitro and in
      vivo experiments has provided evidence that brain CYPs can impact acute and
      chronic drug response, susceptibility to damage by neurotoxins, and are
      associated with altered personality, behaviour, and risk of neurological disease.
      They may also play a role in endogenous neurotransmitter and neurosteroid
      homeostasis. This review goes through the characterization of brain CYPs across
      species, the patterns of susceptibility of brain CYPs to exogenous induction, and
      recent preclinical evidence of the potential role of brain CYPs in vivo (e.g.
      CYP2D), along with the development of experiment paradigms that allow modulation
      of brain CYP activity without affecting CYP activity in the liver. Understanding
      brain CYP function, and changes therein, may provide unique strategies for the
      development of CNS-acting therapeutics metabolized locally in the brain, as well
      as therapeutics to target brain CYPs directly.

PMID- 29024743
TI  - Stenting as a bridge to resection versus emergency surgery for left-sided
      colorectal cancer with malignant obstruction: A systematic review and meta
      analysis.
AB  - PURPOSE: This study aims to discuss the safety and feasibility of a combined
      treatment consisting of stent insertion and elective surgery for left-sided
      colorectal cancer with malignant obstruction. METHODS: Randomized clinical trials
      (RCTs) that discussed the safety and feasibility of stenting as a bridge to
      surgery in malignant colorectal cancer were identified in a search of medical
      databases, including PubMed, Embase, Cochrane Library, and SCIENCE. Each paper's
      quality was assessed using the Jadad scale. A meta-analysis was conducted using
      RevMan 5.3, and statistical heterogeneity between RCTs was defined as I2>50%.
      RESULTS: Nine RCTs included 594 patients were selected and analyzed. Of the
      included patients, 281 underwent stent insertion followed by elective surgery (SG
      group), and 313 underwent emergency surgery (EG group). The meta-analysis
      revealed that the patients in the SG group had a higher one-stage anastomosis
      rate. Patients in the SG had lower mortality rates and minor complications. There
      was no significant difference in anastomotic leakage between the two groups. The
      funnel plot showed that there was no publication bias in these outcomes.
      CONCLUSION: Stenting as a bridge to surgery was safe and feasible in left-sided
      colorectal cancer with malignant obstruction. Compared with the patients in the
      EG group, the SG patients had an improved primary anastomosis rate and
      experienced no increase in the risk of other complications.

PMID- 29024744
TI  - A 2.833-kb Insertion in BnFLC.A2 and Its Homeologous Exchange with BnFLC.C2
      during Breeding Selection Generated Early-Flowering Rapeseed.

PMID- 29024745
TI  - Correlation between extension-block K-wire insertion angle and postoperative
      extension loss in mallet finger fracture.
AB  - INTRODUCTION: Extension-block pinning represents a simple and reliable surgical
      technique. Although this procedure is commonly performed successfully, some
      patients develop postoperative extension loss. To date, the relationship between
      extension-block Kirschner wire (K-wire) insertion angle and postoperative
      extension loss in mallet finger fracture remains unclear. HYPOTHESIS: We aimed to
      clarify this relationship and further evaluate how various operative and non
      operative factors affect postoperative extension loss after extension-block
      pinning for mallet finger fracture. MATERIALS AND METHOD: A retrospective study
      was conducted to investigate a relationship between extension block K-wire
      insertion angle and postoperative extension loss. The inclusion criteria were:
      (1) a dorsal intra-articular fracture fragment involving 30% of the base of the
      distal phalanx with or without volar subluxation of the distal phalanx; and (2)
      <3 weeks delay from the injury without treatment. Extension-block K-wire
      insertion angle and fixation angle of the distal interphalangeal (DIP) joint were
      assessed using lateral radiograph at immediate postoperative time. Postoperative
      extension loss was assessed by using lateral radiograph at latest follow-up.
      Extension-block K-wire insertion angle was defined as the acute angle between
      extension block K-wire and longitudinal axis of middle phalangeal head. DIP joint
      fixation angle was defined as the acute angle between the distal phalanx and
      middle phalanx longitudinal axes. RESULTS: Seventy-five patients were included.
      The correlation analysis revealed that extension-block K-wire insertion angle had
      a negative correlation with postoperative extension loss, whereas fracture size
      and time to operation had a positive correlation (correlation coefficient for
      extension block K-wire angle: -0.66, facture size: +0.67, time to operation:
      +0.60). When stratifying patients in terms of negative and positive fixation
      angle of the DIP joint, the independent t-test showed that mean postoperative
      extension loss is -3.67 degrees  and +4.54 degrees  (DIP joint fixation angles of
      <0 degrees  and >=0 degrees , respectively, P=0.024). When stratifying patients
      in terms of extension-block K-wire insertion angle (30 degrees , 30 degrees -40
      degrees , >40 degrees ), ANOVA showed significantly less postoperative extension
      loss for higher insertion angles (>40 degrees ) than for medium insertion angles
      (30 degrees -40 degrees ). Mean postoperative extension loss difference between
      higher insertion angle (>40 degrees ) and medium insertion angle (30 degrees -40
      degrees ) was 11 degrees  (P=0.002). DISCUSSION: Using an insertion angle of the
      extension-block K-wire of 40 degrees -45 degrees  and a slightly hyperextended
      position of the DIP joint may help reducing postoperative extension loss. LEVEL
      OF EVIDENCE: Therapeutic level III.

PMID- 29024746
TI  - Dynamics of DNA unwinding by helicases with frequent backward steps.
AB  - XPD (Xeroderma pigmentosum complementation group D) is a prototypical 5' - 3'
      translocating DNA helicase that exhibits frequent backward steps during DNA
      unwinding. Here, we propose a model of DNA unwinding by XPD. With the model we
      explain why XPD exhibits frequent backsteps while other helicases show rare
      backsteps. We explain quantitatively the single-molecule data on probability of 
      1-bp step and mean dwell time of one step versus ATP concentration for XPD at
      fixed large external force applied to the ends of the DNA hairpin to unzip the
      hairpin. We study DNA unwinding velocity, probability of -1-bp step and mean
      dwell time of one step for XPD versus external force at various ATP
      concentrations. We compare DNA unwinding dynamics of the 5' - 3' helicase XPD
      with that of 3' - 5' helicase RecQ. Our results show that the DNA unwinding
      velocity of XPD is sensitively dependent on the external force, which is contrast
      to RecQ that shows insensitive dependence of DNA unwinding velocity on the
      external force, explaining the experimental data showing that RecQ is an
      "optimally active" helicase while XPD is a "partially active" helicase. The DNA
      unwinding dynamics of different helicases under the external force is also
      studied.

PMID- 29024747
TI  - Diletter circular codes over finite alphabets.
AB  - The graph approach of circular codes recently developed (Fimmel et al., 2016)
      allows here a detailed study of diletter circular codes over finite alphabets. A
      new class of circular codes is identified, strong comma-free codes. New theorems
      are proved with the diletter circular codes of maximal length in relation to (i)
      a characterisation of their graphs as acyclic tournaments; (ii) their explicit
      description; and (iii) the non-existence of other maximal diletter circular
      codes. The maximal lengths of paths in the graphs of the comma-free and strong
      comma-free codes are determined. Furthermore, for the first time, diletter
      circular codes are enumerated over finite alphabets. Biological consequences of
      dinucleotide circular codes are analysed with respect to their embedding in the
      trinucleotide circular code X identified in genes and to the periodicity modulo 2
      observed in introns. An evolutionary hypothesis of circular codes is also
      proposed according to their combinatorial properties.

PMID- 29024748
TI  - Effect of circulating tumor cell aggregate configuration on hemodynamic transport
      and wall contact.
AB  - Selectin-mediated adhesion of circulating tumor cells (CTCs) to the endothelium
      is a critical step in cancer metastasis, a major factor contributing to the
      mortality of cancer. The formation of tethers between tumor cells and endothelial
      selectins initiates cell rolling, which can lead to firm adhesion, extravasation
      and the formation of secondary metastases. Tumor cells travel through the
      bloodstream as single cells, or as aggregates known as circulating tumor
      microemboli (CTM). CTM have increased survivability and metastatic potential
      relative to CTCs, and the presence of CTM is associated with worse patient
      prognosis. The motion of cells and cellular aggregates in flow is a function of
      their size and shape, and these differences influence the frequency and strength
      of their contact with the endothelium. In this study, a computational model
      consisting of the hydrodynamic component of the Multiparticle Adhesive Dynamics
      simulation analyzed the effects of model aggregate conformation and orientation
      on adhesive binding potential. Model aggregates of the Colo205 colorectal cancer
      cell line were created, consisting of two, three, and four cells in simple
      geometrical conformations. Contact time, contact area, and time integral of
      contact area were measured as a function of fluid shear rate, initial centroid
      height, and initial orientation for model aggregates that experienced
      hydrodynamic collisions with the plane wall. It was found that larger CTM
      conformations with intermediate nonsphericities had the highest adhesion
      potential. The results of this study shed light on the correlation between
      environmental conditions and extravasation efficiency, which could inform the
      development of new anti-metastatic drugs.

PMID- 29024749
TI  - A computational approach to extinction events in chemical reaction networks with
      discrete state spaces.
AB  - Recent work of Johnston et al. has produced sufficient conditions on the
      structure of a chemical reaction network which guarantee that the corresponding
      discrete state space system exhibits an extinction event. The conditions consist
      of a series of systems of equalities and inequalities on the edges of a modified
      reaction network called a domination-expanded reaction network. In this paper, we
      present a computational implementation of these conditions written in Python and
      apply the program on examples drawn from the biochemical literature. We also run
      the program on 458 models from the European Bioinformatics Institute's BioModels
      Database and report our results.

PMID- 29024750
TI  - Mandibular lymphoma.
AB  - INTRODUCTION: B-cell lymphoblastic lymphoma (B-LBL) rarely occurs in the oral
      cavity (3.5% of all intra-oral malignant tumors). Few cases of B-LBL mandibular
      bone involvement have been reported. OBSERVATION: We report the case of a 30-year
      old female patient presenting with a single swelling of the left mandibular
      region, having grown for several weeks. Maxillo-facial CT and MRI showed
      inflammation of soft tissues and muscles without initial signs of osteitis, thus
      noncontributive to the diagnosis. A biopsy allowed diagnosing an intra-oral bone
      lymphoblastic lymphoma. The patient was referred to the hematooncology unit for
      treatment. DISCUSSION: Jaw localization of non Hodgkin's lymphoma is rare.
      Clinical symptomatology and radiological signs are poorly contributive. The
      diagnosis relies on a histopathological analysis.

PMID- 29024751
TI  - Phylogenomics reveals habitat-associated body shape divergence in Oryzias woworae
      species group (Teleostei: Adrianichthyidae).
AB  - The Oryzias woworae species group, composed of O. asinua, O. wolasi, and O.
      woworae, is widely distributed in southeastern Sulawesi, an island in the Indo
      Australian Archipelago. Deep-elongated body shape divergence is evident among
      these three species to the extent that it is used as a species-diagnostic
      character. These fishes inhabit a variety of habitats, ranging from upper streams
      to ponds, suggesting that the body shape divergence among the three species may
      reflect adaptation to local environments. First, our geometric morphometrics
      among eight local populations of this species group revealed that the three
      species cannot be separated by body shape and that riverine populations had more
      elongated bodies and longer caudal parts than lacustrine populations. Second,
      their phylogenetic relationships did not support the presence of three species;
      phylogenies using mitochondrial DNA and genomic data obtained from RNA-Seq
      revealed that the eight populations could not be sorted into three different
      clades representing three described species. Third, phylogenetic corrections of
      body shape variations and ancestral state reconstruction of body shapes
      demonstrated that body shape divergence between riverine and lacustrine
      populations persisted even if the phylogenies were considered and that body shape
      evolved rapidly irrespective of phylogeny. Sexual dimorphism in body shape was
      also evident, but the degree of dimorphism did not significantly differ between
      riverine and lacustrine populations after phylogenetic corrections, suggesting
      that sexual selection may not substantially contribute to geographical variations
      in body shape. Overall, these results indicate that the deep-elongated body shape
      divergence of the O. woworae species group evolved locally in response to habitat
      environments, such as water currents, and that a thorough taxonomic reexamination
      of the O. woworae species group may be necessary.

PMID- 29024752
TI  - Overtraining modifies spatial memory susceptibility to corticosterone
      administration.
AB  - Even though the effects of overtraining and glucocorticoids on different phases
      of spatial memory are known, the interaction between these factors on the
      retrieval and extinction of spatial memory has not yet been described. Adult male
      Wistar rats received eight training trials per day in the Barnes maze for either
      one or two days. Twenty-four hours after the last training trial they were
      randomly assigned for receiving an intraperitoneal vehicle or corticosterone
      injection (0.125 or 0.5 mg/kg) and ten minutes later they were given a memory
      test, followed by seven extinction trials. Extinction retention was evaluated
      twenty-four hours after extinction. The second training session did not provoke
      significant changes regarding escape latency nor weighted errors, thereby showing
      that overtraining had been obtained. The overtrained animals performed better
      than the trained ones during the retrieval test. Corticosterone administration
      did not affect the overtrained animals' performance; by contrast, only the lower
      dose impaired trained animals' retrieval. Overtrained subjects acquired
      extinction more rapidly than those which received just one session, but
      corticosterone did not significantly modify extinction. However, whilst the
      spatial task remained extinguished in trained animals during the extinction
      retrieval test, spontaneous recovery occurred in overtrained animals. Such
      training intensity effects on extinction retrieval were reverted by
      corticosterone. Overall, these results suggested that overtraining modified the
      susceptibility of spatial memory's trace to the effects of corticosterone on
      retrieval and extinction.

PMID- 29024753
TI  - Spread of multidrug-resistant high-risk Klebsiella pneumoniae clones in a
      tertiary hospital from southern Brazil.
AB  - Klebsiella pneumoniae is among the most important pathogens found in hospitals.
      The emergence of multiple antibiotic resistant K. pneumoniae associated with its
      virulence factors is a worldwide concern and its early identification is crucial,
      especially for controlling the spread of emerging clones. This article reports a
      high prevalence of multiresistant K. pneumoniae in a university hospital in
      southern Brazil, harboring several virulence and beta-lactamase encoding genes,
      including pandrug-resistant high-risk international clones belonging to the
      clonal group 258 (ST11, ST15, ST101, ST258, ST340 and ST874).

PMID- 29024754
TI  - Comparison of genetic characteristics of canine papillomaviruses in Turkey.
AB  - Papillomavirus (PV) infections often cause benign and malignant skin neoplasia in
      dogs. To date, twenty types of canine papillomaviruses (CPVs) have been described
      worldwide. A detailed molecular characterization of CPVs in Turkey is lacking. In
      the present study, oral and mucosal lesions from 13 dogs with suspected CPV
      infection from the Mediterranean and central Anatolian regions of Turkey were
      analyzed. The partial gene sequences of the L1, E6, and E7 regions were compared
      with those of CPV types in the GenBank database. The results showed that CPV-1
      infection was the dominant type of canine papillomatosis in Turkey. In addition,
      there was no statistically significant association between the frequency of the
      disease and the age or gender of the dog (p>0.05). However, all the dogs were
      pedigree breeds, suggesting that the disease may be more prevalent among pure
      bred dogs than mixed breeds.

PMID- 29024755
TI  - Performance of Pediatric Rehabilitation Medicine Candidates on the Subspecialty
      Board Certification Examination from 2003 to 2015.
AB  - BACKGROUND: Pediatric rehabilitation medicine (PRM) physicians enter the field
      via several pathways. It is unknown whether different training pathways impact
      performance on the American Board of Physical Medicine and Rehabilitation (ABPMR)
      PRM Examination and Maintenance of Certification (MOC) Examination. OBJECTIVES:
      To describe the examination performance of candidates on the ABPMR PRM
      Examination according to their type of training (physiatrists with a clinical PRM
      focus, accredited or unaccredited fellowship training, separate pediatric and
      physical medicine and rehabilitation residencies, or combined pediatrics/physical
      medicine and rehabilitation residencies) and to compare candidates' performance
      on the PRM Examination with their initial ABPMR certification and MOC
      Examinations. DESIGN: A retrospective cohort study. SETTING: American Board of
      Physical Medicine and Rehabilitation office. PARTICIPANTS: A total of 250
      candidates taking the PRM subspecialty certification examination from 2003 to
      2015. METHODS: Scaled scores on the PRM Examination were compared to the
      examinees' initial certification scores as well as their admissibility criteria.
      Pass rates and scaled scores also were compared for those taking their initial
      PRM certification versus MOC. MAIN OUTCOME MEASUREMENTS: Board pass rates and
      mean scaled scores for initial PRM Examination and MOC. RESULTS: The 250
      physiatrists who took the subspecialty PRM Examination had an overall first-time
      pass rate of 89%. There was no significant difference between first-time PRM pass
      rates or mean scaled scores for individuals who completed an Accreditation
      Council for Graduate Medical Education-accredited fellowship versus those who did
      not. First time PRM pass rates were greatest among those who were also certified
      by the American Board of Pediatrics (100%). Performance on Parts I and II of the
      initial ABPMR Certification Examination significantly predicted PRM Examination
      scores. There was no difference in mean scaled scores for initial PRM
      certification versus taking the PRM Examination for MOC. CONCLUSIONS: Several
      pathways to admissibility to the PRM Examination afforded similar opportunity for
      diplomates to gain the knowledge necessary to pass the PRM Examination. Once
      certified, physicians taking the PRM Examination for MOC have a high success rate
      of passing again in years 7-10 of their certification cycle. LEVEL OF EVIDENCE:
      III.

PMID- 29024756
TI  - Treatment Strategies and Prognostic Factors of Limited-Stage Primary Small Cell
      Carcinoma of the Esophagus.
AB  - INTRODUCTION: Primary small cell carcinoma of the esophagus (PSCCE) is
      characterized by high malignancy, early metastasis, and poor prognosis. This
      retrospective study aimed to review the clinical characteristics of patients with
      limited-stage PSCCE and determine the relevant prognostic factors and optimal
      treatment strategies. METHODS: We retrospectively evaluated 152 consecutive
      patients with limited-stage PSCCE between January 2007 and December 2015.
      Prognostic factors were analyzed using univariate analysis and a Cox regression
      model. Subgroup analysis was applied to evaluate the effect of treatment strategy
      on survival. RESULTS: Univariate and multivariate analyses showed that treatment
      modality (p = 0.034) and N stage (p = 0.002) were independent prognostic factors.
      Patients with stage I or IIA PSCCE who underwent an operation alone exhibited
      better survival than those who did not undergo an operation (median survival time
      29 versus 17.4 months [p = 0.031]), and postoperative adjuvant therapy did not
      increase overall survival or disease-free survival (p > 0.05). The overall
      survival rate of patients with stage III PSCCE who underwent neoadjuvant
      chemotherapy (nCT) was significantly better than that of patients who underwent
      an operation alone or did not undergo an operation (p = 0.021 and p = 0.026,
      respectively); additionally, nCT could increase disease-free survival (p =
      0.031). CONCLUSIONS: Treatment modalities and N stage are independent prognostic
      factors. Radical esophagectomy should be considered as the primary treatment for
      stage I or IIA PSCCE, and nCT followed by esophagectomy could be an effective
      treatment option for stage III PSCCE. Multicenter randomized studies are required
      to confirm the role of nCT in the management of limited-stage PSCCE.

PMID- 29024757
TI  - A meta-analysis on the correlation between admission hyperglycemia and myocardial
      infarct size on CMRI.
AB  - AIMS: The aim was to compare the size of the myocardial infarct detected on
      cardiovascular magnetic resonance imaging (CMR) between patients with and without
      admission hyperglycemia after acute myocardial infarction (AMI). METHODS: Studies
      were identified by searching on MEDLINE, EMBASE, and CINAHL databases. A
      systematic review was conducted by two independent reviewers. Microvascular
      obstruction (MVO) and late gadolinium enhancement (LGE) were pooled from
      available studies to calculate the standardized mean difference (SMD) in post-MI
      infarct size between patients with and without hyperglycemia at admission.
      RESULTS: The systematic review yielded 5 studies with MCR data for patients with
      and without admission hyperglycemia. The total number of patients included in
      this study was 911. A statistically significant difference was detected in MVO
      between patients with and without admission hyperglycemia (SMD = 0.79, 95% CI:
      0.11, 1.47, P < 0.00001). The difference in LGE between patients with and without
      admission hyperglycemia was also significant (SMD = 0.57, 95% CI: -0.04, 1.18, P
      < 0.00001). CONCLUSION: The main finding of our analyses is that the size of
      myocardial infarct detected on CMR is positively correlated to admission
      hyperglycemia in patients with AMI. The clinical importance of this study lies in
      the accurate assessment of prognostic value of admission glucose, which would
      help clinicians in risk stratification and treatment decision-making.

PMID- 29024759
TI  - Specificity of plant membrane trafficking - ARFs, regulators and coat proteins.
AB  - Approximately one-third of all eukaryotic proteins are delivered to their
      destination by trafficking within the endomembrane system. Such cargo proteins
      are incorporated into forming membrane vesicles on donor compartments and
      delivered to acceptor compartments by vesicle fusion. How cargo proteins are
      sorted into forming vesicles is still largely unknown. Here we review the roles
      of small GTPases of the ARF/SAR1 family, their regulators designated ARF guanine
      nucleotide exchange factors (ARF-GEFs) and ARF GTPase-activating proteins (ARF
      GAPs) as well as coat protein complexes during membrane vesicle formation.
      Although conserved across eukaryotes, these four functional groups of proteins
      display plant-specific modifications in composition, structure and function.

PMID- 29024758
TI  - PCR-ribotype distribution of Clostridium difficile in Irish pigs.
AB  - Clostridium difficile is an important enteric pathogen in humans causing
      infections in the healthcare environment and the community. Carriage of C.
      difficile and C. difficile-related enterocolitis has been reported in piglets
      worldwide. The aim of this study was to investigate the rates of C. difficile
      isolation from pigs in Ireland. Faecal samples from piglet litters and sows were
      collected from six farms in 2015. The sows were non-diarrhoeal at the time of
      sampling. The diarrhoeal status of the piglets was unknown. C. difficile was
      isolated from 34/44 (77%) of piglet litter samples and from 33/156 (21%) of sow
      samples. The isolation rate in sows varied from 3 to 39% and in piglet litters
      from 72 to 86% depending on farm location. Toxin A and toxin B were present in
      99% (66/67) of isolates; and binary toxin in 85% (57/67). Only PCR-ribotypes 078
      (88%) and 193 (12%) were identified in piglets. Seven PCR-ribotypes were detected
      in sow C. difficile isolates: PCR-ribotypes 078 (67%), 050 (12%), 014/020 (6%),
      015 (6%), 029 (3%), 035 (3%) and 193 (3%). This study shows that toxigenic C.
      difficile strains such as PCR-ribotype 078 can be commonly isolated from pigs at
      different geographical locations in Ireland. Since PCR-ribotype 078 is frequently
      found in humans in Ireland, this highlights the potential for interspecies
      transmission.

PMID- 29024760
TI  - RNA processing in the male germline: Mechanisms and implications for fertility.
AB  - Mammalian spermatogenesis is a tightly coordinated process that gives rise to
      mature spermatozoa capable of fertilising an ovum during sexual reproduction. A
      population of stem and progenitor cells known as undifferentiated spermatogonia
      enables continual spermatogenesis throughout life. A complex transcriptional
      network that balances self-renewal of spermatogonia with their timely
      differentiation in order to maintain constant fertility regulates this process.
      Importantly, post-transcriptional regulation of gene expression plays a critical
      role in spermatogenesis, necessitated by the profound genetic and morphological
      changes that occur during meiosis and sperm maturation. Pre-mRNA splicing, mRNA
      export, maintenance of transcript stability and translation are key RNA
      processing steps that are regulated in the male germline to maintain coordinated
      gene expression. In this review, we examine these processes in the context of
      mammalian spermatogenesis and provide an overview of key mediators at each step.

PMID- 29024761
TI  - Pattern of Closure of Skull Base Synchondroses in Crouzon Syndrome.
AB  - BACKGROUND: The age of closure of skull base synchondroses has never been
      analyzed in a homogenous population of children with Crouzon syndrome. METHODS: A
      retrospective case-control study was performed on 30 Crouzon children (17 male,
      13 female) aged 1 month to 12.48 years with Fibroblast Growth Factor Receptor
      type 2 mutation. Eleven synchondroses were analyzed on millimetric computed
      tomodensitometric slices before surgery. Syndromic patients were compared with a
      series of 235 healthy children previously published. RESULTS: Synchondrosis
      closure follows a global pattern that occurs earlier in Crouzon syndrome than in
      controls (P <= 0.002). Synchondrosis fusion starts at 10 months of age with
      posterior intraoccipital synchondroses and lambdoid sutures, followed by
      occipitomastoid synchondroses between 1.85 (right) and 2.27 years (left) and
      anterior intraoccipital synchondroses at approximately 2.80 years. Time to
      complete fusion varies considerably according to the synchondroses. Spheno
      occipital and petro-occipital synchondroses fuse last, at approximately 3 years
      old. CONCLUSIONS: In children with Crouzon syndrome, synchondrosis closure occurs
      prematurely, with a time course specific to each synchondrosis.

PMID- 29024762
TI  - A paired comparison study on refractive changes after strabismus surgery.
AB  - PURPOSE: To quantify refractive changes following horizontal lateral rectus
      recession and medial rectus resection surgery and to investigate the causes of
      these changes. METHODS: The medical records of patients who underwent unilateral
      horizontal lateral rectus recession and medial rectus resection for exotropia by
      a single surgeon over a period of 14 years were reviewed retrospectively. Using
      vector analysis, refractive changes in operated eyes (cases) were compared to
      changes in the sound eyes (controls). The main outcome measures were differences
      in mean change of refractive parameters and the proportion of clinically
      significant changes. RESULTS: A total of 31 subjects (median age, 13.6 years;
      interquartile range, 8.8-19.8 years) were included. A significantly higher
      magnitude of refractive changes was observed in the operated eyes (P = 0.001). In
      addition, the proportion of cases with clinically significant change in sphere or
      cylinder was significantly higher in the operated eyes compared to the sound eyes
      (48% vs 10% [OR = 2.31, P = 0.002] and 32% vs 10% [OR = 5.0, P = 0.039], resp.).
      CONCLUSIONS: Horizontal strabismus surgery is associated with refractive changes
      that might be of clinical significance. Pediatric ophthalmologists should
      consider re-refraction 1 month postoperatively.

PMID- 29024764
TI  - "It's Pretty Hard to Tell Your Mom and Dad That You're on a Method": Exploring
      How an App Could Promote Adolescents' Communication with Partners and Parent(s)
      to Increase Self-Efficacy in Long-Acting Reversible Contraception Use.
AB  - STUDY OBJECTIVE: Youth-friendly information and support are integral components
      to promote adolescents' successful use of long-acting reversible contraception
      (LARC), and smartphone apps offer a promising medium. To inform content
      development for an app guided by the Health Belief Model, we conducted interviews
      with adolescent LARC users to assess self-efficacy and experiences with LARC,
      their communication with partners and parent(s) about LARC, and how apps could
      support this communication. DESIGN, SETTING, AND PARTICIPANTS: We conducted
      semistructured, in-depth interviews with 30 female adolescent LARC users enrolled
      in urban school-based health centers. INTERVENTIONS AND MAIN OUTCOME MEASURES:
      Descriptive analyses were used to assess demographic characteristics, experience
      and comfort communicating with current and future partners and parent(s) about
      LARC, self-efficacy around LARC, and how app elements could support LARC use.
      RESULTS: Participants (mean age, 16 years; range, 14-19 years) were predominately
      Hispanic (77%; n = 23) and black (20%; n = 6). Almost all (97%; n = 29) had told
      their current partner about their LARC, but of these, only 15 (50%) would feel
      comfortable talking with a new sexual partner. Most participants (73%; n = 22)
      had not told their parent(s) about getting a LARC, but many reported they were
      likely to share app information with their parent(s). Of the few participants who
      did tell their parent(s), 38% (n = 3) reported that it was difficult to do so.
      Adolescents described ways in which app use could help initiate conversations
      with new partners and parent(s). CONCLUSION: These findings suggest the potential
      of a theory-based smartphone app to meet adolescent LARC users' information and
      support needs. The app should include information on strategies for communicating
      with future partners and parent(s).

PMID- 29024763
TI  - Slow reading in children with anisometropic amblyopia is associated with fixation
      instability and increased saccades.
AB  - BACKGROUND: Previous studies show slow reading in strabismic amblyopia. We
      recently identified amblyopia, not strabismus, as the key factor in slow reading
      in children. No studies have focused on reading in amblyopic children without
      strabismus. We examined reading in anisometropic children and evaluated whether
      slow reading was associated with ocular motor dysfunction in children with
      amblyopia. METHODS: Anisometropic children (7-12 years) with or without amblyopia
      were compared to age-similar normal controls. Children silently read a grade
      appropriate paragraph during binocular viewing. Reading rate (words/min), number
      of forward and regressive saccades (per 100 words) and fixation duration were
      recorded with the ReadAlyzer. Binocular fixation instability was also evaluated
      (EyeLink 1000). RESULTS: Amblyopic anisometropic children read more slowly (n =
      25; mean with standard deviation, 149 +/- 42 words/min) than nonamblyopic
      anisometropic children (n = 15; 196 +/- 80 words/min; P = 0.024) and controls (n
      = 25; 191 +/- 65 words/min; P = 0.020). Nonamblyopic anisometropic children read
      at a comparable rate to controls (P = 0.81). Slow reading in amblyopic
      anisometropic children was correlated with increased forward saccades (r = -0.84,
      P < 0.001), increased regressive saccades (r = -0.85, P < 0.001), and fellow eye
      instability during binocular viewing (r = -0.52, P = 0.019). CONCLUSIONS: Slow
      reading in school-age children with anisometropic amblyopia is related to
      increased frequency of saccades and fixation instability of the fellow eye.
      Further research should consider the effects of slower reading on academic
      performance.

PMID- 29024765
TI  - Identification of 2'-deoxy-2'-fluorocytidine as a potent inhibitor of Crimean
      Congo hemorrhagic fever virus replication using a recombinant fluorescent
      reporter virus.
AB  - Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne orthonairovirus,
      causes a severe hemorrhagic disease in humans (Crimean-Congo hemorrhagic fever,
      CCHF). Currently, no vaccines are approved to prevent CCHF; treatment is limited
      to supportive care and the use of ribavirin, the therapeutic benefits of which
      remain unclear. CCHF is part of WHO's priority list of infectious diseases
      warranting further research and development. To aid in the identification of new
      antiviral compounds, we generated a recombinant CCHFV expressing a reporter
      protein, allowing us to quantify virus inhibition by measuring the reduction in
      fluorescence in infected cells treated with candidate compounds. The screening
      assay was readily adaptable to high-throughput screening (HTS) of compounds using
      Huh7 cells, with a signal-to-noise ratio of 50:1, and Z'-factors > 0.6 in both 96
      and 384-well formats. A screen of candidate nucleoside analog compounds
      identified 2'-deoxy-2'-fluorocytidine (EC50 = 61 +/- 18 nM) as having 200 * the
      potency of ribavirin (EC50 = 12.5 +/- 2.6 MUM), as well as 17 * the potency of T
      705 (favipiravir), another compound with reported anti-CCHFV activity (EC50 =
      1.03 +/- 0.16 MUM). Furthermore, we also determined that 2'-deoxy-2'
      fluorocytidine acts synergistically with T-705 to inhibit CCHFV replication
      without causing cytotoxicity. The incorporation of this reporter virus into the
      high-throughput screening assay described here will allow more rapid
      identification of effective therapeutic options to combat this emerging human
      pathogen.

PMID- 29024767
TI  - Modulation of proteolytic polyprotein processing by coxsackievirus mutants
      resistant to inhibitors targeting phosphatidylinositol-4-kinase IIIbeta or
      oxysterol binding protein.
AB  - Enteroviruses (e.g. poliovirus, coxsackievirus, and rhinovirus) require several
      host factors for genome replication. Among these host factors are
      phosphatidylinositol-4-kinase IIIbeta (PI4KB) and oxysterol binding protein
      (OSBP). Enterovirus mutants resistant to inhibitors of PI4KB and OSBP were
      previously isolated, which demonstrated a role of single substitutions in the non
      structural 3A protein in conferring resistance. Besides the 3A substitutions
      (i.e., 3A-I54F and 3A-H57Y) in coxsackievirus B3 (CVB3), substitution N2D in 2C
      was identified in each of the PI4KB-inhibitor resistant CVB3 pools, but its
      possible benefit has not been investigated yet. In this study, we set out to
      investigate the possible role of 2C-N2D in the resistance to PI4KB and OSBP
      inhibition. We show that 2C-N2D by itself did not confer any resistance to
      inhibitors of PI4KB and OSBP. However, the double mutant (i.e., 2C-N2D/3A-H57Y)
      showed better replication than the 3A-H57Y single mutant in the presence of
      inhibitors. Growing evidence suggests that alterations in lipid homeostasis
      affect the proteolytic processing of the poliovirus polyprotein. Therefore, we
      studied the effect of PI4KB or OSBP inhibition on proteolytic processing of the
      CVB3 polyprotein during infection as well as in a replication-independent system.
      We show that both PI4KB and OSBP inhibitors specifically affected the cleavage at
      the 3A-3B junction, and that mutation 3A-H57Y recovered impaired proteolytic
      processing at this junction. Although 2C-N2D enhanced replication of the 3A-H57Y
      single mutant, we did not detect additional effects of this substitution on
      polyprotein processing, which leaves the mechanism of how 2C-N2D contributes to
      the resistance to be revealed.

PMID- 29024766
TI  - Protective effect of an alpha 7 nicotinic acetylcholine receptor agonist against
      enterovirus 71 infection in neuronal cells.
AB  - Enterovirus 71, as one of the dominant pathogens associated with severe hand,
      foot, and mouth disease, has been well reported to trigger severe neurological
      symptoms among young children over the last decade, particularly among children
      in the Asia-Pacific region. To date, no effective antiviral agent has been
      developed for the treatment of severe enterovirus 71 infection. PNU-282987, a
      selective alpha 7 nicotinic acetylcholine receptor (alpha7nAChR) agonist, has
      been reported to have a neuroprotective effect by participating in inflammatory
      regulation in previous studies. Therefore, in the present study, we aimed to
      assess the cell-protective effect of PNU-282987 against enterovirus 71 infection
      in neuronal cells, and to discuss potential mechanisms underlying this cell
      protective effect in order to elucidate the potential impact of such agonists in
      the treatment of neurotropic viral infection. We observed that treatment with PNU
      282987 improved cell viability and inhibited viral replication in enterovirus 71
      infected SH-SY5Y cells. Further investigation revealed that inhibition of
      enterovirus 71 production by PNU-282987 is likely associated with events of RNA
      replication, and that increased levels of INF mRNA and its downstream antiviral
      proteins stimulated by the JAK-STAT2 pathway may contribute to the antiviral
      effect of PNU-282987. Moreover, our findings suggest that both the antiviral and
      anti-inflammatory effects of PNU-282987 may contribute to the neural protective
      effect of the drug in enterovirus 71-infected cells. Taken together, the results
      suggest that selective alpha7nAChR agonists may represent viable candidates for
      future therapeutic treatment of severe enterovirus 71 infection, and for other
      cases of neurotropic viral infection.

PMID- 29024768
TI  - WITHDRAWN: Brucellosis as Unusual Cause for RUQ Pain with Elevated Liver
      Chemistry in the United States.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
      business/policies/article-withdrawal.

PMID- 29024769
TI  - Identification of a single p19 gene and three p40 paralogues in grass carp
      (Ctenopharyngodon idellus): Their potential for the formation of interleukin 23
      and inducible expression in vitro and in vivo.
AB  - Interleukin (IL-) 23, a member of IL-12 family, is a composite cytokine with the
      subunits of p19 and p40. Although IL-12 and IL-23 share the p40 subunit, they
      play vastly different roles in immune regulation. In teleost, much emphasis has
      been placed on the identification of IL-12, but evidence for the existence of IL
      23 is still lacking. In the present study, a p19 gene and three p40 paralogues
      were isolated and identified from grass carp, suggesting multiple assembly of IL
      23 molecules in fish species. To address this issue, the existence of different
      p19/p40 heterodimers were examined by Co-Immunoprecipitation (Co-IP) assay,
      showing that only co-expression of p19 and each p40 subunit could produce the
      soluble proteins corresponding to three IL-23 isoforms. Additionally, bacterial
      infection could up-regulate the mRNA expression of p19, p40a and p40b but not
      p40c in head kidney, indicating distinct expression patterns of three p40
      paralogues. Moreover, in vitro experiments demonstrated that both B-cell
      stimulator, LPS and T-cell mitogen, PHA markedly increased the mRNA levels of p19
      and three p40 paralogues in grass carp periphery blood lymphocytes (PBLs). The
      simultaneous up-regulation of mRNA expression of p19 and p40 paralogues in
      response to immune stimuli supports the idea that p19 may form heterodimeric
      molecules with three p40 subunits in grass carp under immune activation. These
      findings for the first time highlight the potential of p19 and p40 for
      dimerization in fish, particularly the existence of three IL-23 isoforms as
      soluble heterodimeric cytokines in grass carp, thereby providing the basis for
      further investigating the function of IL-23 in fish immunity.

PMID- 29024770
TI  - Biochemical, biological and molecular characterization of an L-Amino acid oxidase
      (LAAO) purified from Bothrops pictus Peruvian snake venom.
AB  - An L-amino acid oxidase from Peruvian Bothrops pictus (Bpic-LAAO) snake venom was
      purified using a combination of size-exclusion and ion-exchange chromatography.
      Bpic-LAAO is a homodimeric glycosylated flavoprotein with molecular mass of ~65
      kDa under reducing conditions and ~132 kDa in its native form as analyzed by SDS
      PAGE and gel filtration chromatography, respectively. N-terminal amino acid
      sequencing showed highly conserved residues in a glutamine-rich motif related to
      binding substrate. The enzyme exhibited optimal activity towards L-Leu at pH 8.5,
      and like other reported SV-LAAOs, it is stable until 55  degrees C. Kinetic
      studies showed that the cations Ca2+, Mg2+ and Mn2+ did not alter Bpic-LAAO
      activity; however, Zn2+ is an inhibitor. Some reagents such as beta
      mercaptoethanol, glutathione and iodoacetate had inhibitory effect on Bpic-LAAO
      activity, but PMSF, EDTA and glutamic acid did not affect its activity. Regarding
      the biological activities of Bpic-LAAO, this enzyme induced edema in mice (MED =
      7.8 MUg), and inhibited human platelet aggregation induced by ADP in a dose
      dependent manner and showed antibacterial activity on Gram (+) and Gram (-)
      bacteria. Bpic-LAAO cDNA of 1494 bp codified a mature protein with 487 amino acid
      residues comprising a signal peptide of 11 amino acids. Finally, the phylogenetic
      tree obtained with other sequences of LAAOs, evidenced its similarity to other
      homologous enzymes, showing two well-established monophyletic groups in Viperidae
      and Elapidae families. Bpic-LAAO is evolutively close related to LAAOs from B.
      jararacussu, B. moojeni and B. atrox, and together with the LAAO from B.
      pauloensis, form a well-defined cluster of the Bothrops genus.

PMID- 29024771
TI  - Development of dot-ELISA for the detection of venoms of major Indian venomous
      snakes.
AB  - India remained an epicenter for the snakebite-related mortality and morbidities
      due to widespread agricultural activities across the country and a considerable
      number of snakebites offended by Indian cobra (Naja naja), common krait (Bungarus
      caeruleus), Russell's viper (Daboia russelii), and saw-scaled viper (Echis
      carinatus). Presently, there is no selective test available for the detection of
      snake envenomation in India before the administration of snake antivenin.
      Therefore, the present study aimed to develop rapid, sensitive assay for the
      management of snakebite, which can detect venom, responsible snake species and
      serve as a tool for the reasonable administration of snake antivenin, which have
      scarcity across the world. The selective envenomation detection assay needs venom
      specific antibodies (VSAbs) for that monovalent antisera was prepared by
      hyperimmunization of rabbits with specific venom. However, obtained antibodies
      exhibit maximum activity towards homologous venom as well as quantifiable degree
      of cross-reactivity with heterologous venoms. Use of these antibodies for
      development of selective envenomation detection assay may create ambiguity in
      results, therefore needs to isolate VSAbs from monovalent antisera. The cross
      reacting antibodies were specifically removed by immunoaffinity chromatography to
      obtain VSAbs. For the development of venom detection ELISA test (VDET), two
      different species of antibodies were used that offers enhanced sensitivity along
      with selective identification of the venoms of the responsible snakes. In
      conclusion, the developed VDET is rapid, specific, yet sensitive to detect venoms
      of offending snake species, and its venom concentration down to 1.0 ng/ml.
      However, the device observed with lowest venom concentration detection ability in
      the range <1.0 ng/ml from experimentally envenomated samples. The implementation
      of VDET will help in avoiding unnecessary usage and adverse reactions of snake
      antivenin. The test has all the merits to become a choice of method in
      envenomation diagnosis from medically important snakes of India.

PMID- 29024772
TI  - Microcystin-LR leads to oxidative damage and alterations in antioxidant defense
      system in liver and gills of Brycon amazonicus (SPIX & AGASSIZ, 1829).
AB  - Microcystin's (MCs) are toxins produced by several groups of cyanobacteria, in
      water bodies throughout the world, in a process which is being intensified by
      human action. Among the variants of MCs, MC-LR stands out for its distribution
      and toxicity. MCs are potent inhibitors of protein phosphatases 1 and 2 A, which
      causes disruption of the cytoskeleton and consequent cell death. They can also
      alter the antioxidant system and induce oxidative stress in various organs of
      many species. There is, however, a lack of information about the effects of MCs
      on the antioxidant system and oxidative damage in Brazilian fishes. This study
      evaluated the effect of microcystin-LR on the antioxidant system in liver and
      gills of the Brazilian fish Brycon amazonicus, after 48 h of i.p injection of 100
      MUg MC-LR.kg-1 body mass. The liver exhibited increases in the activity of GST
      (74%) and GPx (217%), and a 47% decrease in SOD activity, with no changes in CAT
      values. In the gills of fish exposed to MC-LR, CAT and GPx activities did not
      show significant changes, while SOD and GST activity decreased by 66% and 37%,
      respectively. The GSH content did not change significantly in the liver, however,
      a decrease of 43% was observed in the gills. Oxidative damage measured by protein
      oxidation (PC) and lipoperoxidation (LPO) showed significant effects in both
      tissues. In hepatic tissue, there was no change in PC levels but LPO increased by
      116%. Conversely, in the gills LPO levels did not change but PC increased by
      317%. In conclusion, these data show that MC-LR induces oxidative damage in both
      tissues but in different ways, with being liver most sensitive to LPO and gills
      to PC. This also suggests that the gills are most sensitive to oxidative stress
      than liver, due to the inhibition of its antioxidant responses following MC-LR
      exposure.

PMID- 29024773
TI  - An improved technique for the assessment of venom-induced haemorrhage in a murine
      model.
AB  - Haemorrhage is a common clinical manifestation in envenomings caused by bites
      from snakes of the family Viperidae. Therefore, knowing the haemorrhagic
      potential of venoms and the capacity of antivenoms to neutralise this effect are
      of paramount relevance in toxinology. The most widely used method for quantifying
      haemorrhage involves the intradermal injection of venom (or a mixture of
      venom/antivenom) in mice, and the assessment of the resulting haemorrhagic area
      in the inner side of the skin. Although this method allows a straightforward
      assessment of the haemorrhagic activity of a venom, it does not account for
      haemorrhagic lesions having a similar area but differing in the depth and
      intensity of haemorrhage. We have developed an approach that allows the
      assessment of both area and intensity of a venom-induced haemorrhagic lesion
      using computational tools and propose a unit to represent the combination of
      these two factors as a measure of haemorrhage intensity, namely haemorrhagic unit
      (HaU). A strong correlation was observed between haemoglobin extracted from a
      haemorrhagic lesion and the associated HaUs. The method was used to determine the
      haemorrhagic activity of the venoms of Bothrops asper, Echis ocellatus and
      Crotalus basiliscus and the haemorrhage neutralising capabilities of the three
      associated antivenoms. Overall, the ease of use, as well as the time involved in
      this new method, makes its implementation very feasible in the determination of
      haemorrhagic activity of venoms and its neutralisation by antivenoms in the
      murine model.

PMID- 29024775
TI  - Deciphering the complete deletion of the mgrB locus in an unusual colistin
      resistant Klebsiella pneumoniae isolate colonising the gut of a traveller
      returning from India.

PMID- 29024774
TI  - Evaluation of antibacterial potential of mangrove sediment-derived actinomycetes.
AB  - Actinomycetes are well-known as the source of bioactive metabolites. In this
      work, 16 out of 118 (13.6%) isolates of mangrove sediment-derived actinomycetes
      showed potential antibacterial activity against at least one bacterial strain.
      Five extracts from isolates AMA11, AMA12 and AMA21 exhibited a broad spectrum
      antibacterial activity against Staphylococcus aureus ATCC25923, Staphylococcus
      epidermidis ATCC35984, methicillin-resistant S. aureus (MRSA) SK1, Acinetobacter
      baumannii NPRC004 and Escherichia coli ATCC25922. Ethyl acetate extract from the
      cells of AMA11 (AMA11CE) showed high activity against S. aureus and MRSA with the
      lowest minimum inhibitory concentration (MIC) of 0.5 MUg ml-1. At concentration
      of four times its MIC, AMA11CE destroyed MRSA cells as analysed by the scanning
      electron microscopy. In addition, AMA11CE, ethyl acetate extract from the culture
      broth of AMA12 (AMA12BE), AMA12CE and AMA21CE reduced violacein production in
      Chromobacterium violaceum. Furthermore, at concentrations lower than 10 MUg ml-1,
      all five extracts inhibited biofilm formation by S. epidermidis ATCC35984. The
      chemical analysis of the most active fraction from AMA11CE by GC-MS revealed the
      presence of 3-nitro-1,2-benzenedicarboxylic acid, hexadecanoic acid, quinoxaline
      2-carboxamide and pentadecanoic acid. The 16S rDNA sequencing analysis revealed
      that these three potential isolates belonged to the genus Streptomyces. The
      results revealed that the actinomycetes from mangrove environment would be a good
      source of bioactive metabolites against pathogenic bacteria.

PMID- 29024777
TI  - Validation redefined.

PMID- 29024776
TI  - Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including
      recommendations to assess TILs in residual disease after neoadjuvant therapy and
      in carcinoma in situ: A report of the International Immuno-Oncology Biomarker
      Working Group on Breast Cancer.
AB  - Morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast
      cancer is gaining momentum as evidence strengthens the clinical relevance of this
      immunological biomarker. TILs in the post-neoadjuvant residual disease setting
      are acquiring increasing importance as a stratifying marker in clinical trials,
      considering the raising interest on immunotherapeutic strategies after
      neoadjuvant chemotherapy. TILs in ductal carcinoma in situ, with or without
      invasive carcinoma, represent an emerging area of clinical breast cancer
      research. The aim of this report is to update pathologists, clinicians and
      researchers on TIL assessment in both the post-neoadjuvant residual disease and
      the ductal carcinoma in situ settings. The International Immuno-Oncology Working
      Group proposes a method for assessing TILs in these settings, based on the
      previously published International Guidelines on TIL Assessment in Breast Cancer.
      In this regard, these recommendations represent a consensus guidance for
      pathologists, aimed to achieve the highest possible consistency among future
      studies.

PMID- 29024778
TI  - Direct comparison between in vivo and in vitro microsized particle phagocytosis
      assays in Drosophila melanogaster.
AB  - The effects of micro and nanoparticles on the innate immune system have been
      widely investigated and a general lack of agreement between in vivo and in vitro
      assays has been observed. In order to determine the origin of these
      discrepancies, there is a need for comparing the results of in vivo and in vitro
      phagocytosis assays obtained using the same particles and same immune cells.
      Here, we establish an in vivo polystyrene microsized particle phagocytosis assay
      in Drosophila melanogaster and compare it with an in vitro assay consisting of
      exposing the same immune cells in culture to the same particles. The distribution
      of number of phagocytized beads per cell was shifted to lower numbers of beads
      per cell in the case of the in vitro assay compared to the in vivo assay, which
      we suggest is partly due to a reduced amount of membrane available in cultured
      cells.

PMID- 29024779
TI  - Kinetic characterization of bile salt transport by human NTCP (SLC10A1).
AB  - The transport of bile acids facilitated by NTCP is an important factor in
      establishing bile flow. In this study, we examine the kinetics associated with
      human NTCP-dependent transport of two quantitatively important bile acids
      comprising the human bile acid pool, chenodeoxycholic acid and glycine
      chenodeoxycholate, and secondary bile salt, 3-sulfo-glycolithocholate of
      potential toxicological significance. The study employed human NTCP
      overexpressing Chinese Hamster Ovary cells and results compared with
      taurocholate, a prototypical bile salt commonly used in transporter studies. GCDC
      and 3S-GLC but not CDCA were transported by NTCP. The efficient uptake of GCDC,
      TCA and 3S-GLC by NTCP enabled the determination of kinetics. GCDC displayed a
      lower KM (0.569+/-0.318MUM) than TCA (6.44+/-3.83MUM) and 3S-GLC (3.78+/
      1.17MUM). The apparent CLint value for GCDC was 20-fold greater (153+/-53MUl/mg
      protein/min) than the apparent CLint for TCA (6.92+/-4.72MUl/mg protein/min) and
      apparent CLint for 3S-GLC (8.05+/-1.33MUl/mg protein/min). These kinetic results
      provide important complementary data on the substrate selectivity and specificity
      of NTCP to transport bile acids. NTCP transports GCDC with greater efficiency
      than TCA and has the same efficacy for 3S-GLC and TCA.

PMID- 29024780
TI  - Toxicogenomics of the flame retardant tris (2-butoxyethyl) phosphate in HepG2
      cells using RNA-seq.
AB  - Tris (2-butoxyethyl) phosphate (TBOEP) is a compound produced at high volume that
      is used as both a flame retardant and a plasticizer. It is persistent and
      bioaccumulative, yet little is known of its toxicological modes of action. Such
      insight may aid risk assessment in a weight-of-evidence approach supplementing
      current testing strategies. We used an RNA sequencing approach as an unbiased and
      sensitive tool to explore potential negative health effects of sub-cytotoxic
      concentrations of TBOEP on the transcriptome of the human liver hepatocellular
      carcinoma cell line, HepG2, with the lowest concentration used potentially
      holding relevance to human physiological levels. Over-representation and gene set
      enrichment analysis corresponded well and revealed that TBOEP treatments resulted
      in an upregulation of genes involved in protein and energy metabolism, along with
      DNA replication. Such increases in cell and macromolecule metabolism could
      explain the increase in mitochondrial activity at lower TBOEP concentrations. In
      addition, TBOEP affected a wide variety of biological processes, the most notable
      one being the general stress response, wound healing. Finally, TBOEP showed
      effects on steroid hormone biosynthesis and activation, regulation, and
      potentiation of immune responses, in agreement with other studies. As such, this
      study is the first study investigating genome-wide changes in gene transcription
      in response to TBOEP in human cells.

PMID- 29024781
TI  - The role of androgen receptors in atherosclerosis.
AB  - Male disadvantage in cardiovascular health is well recognised. However, the
      influence of androgens on atherosclerosis, one of the major causes of many life
      threatening cardiovascular events, is not well understood. With the dramatic
      increase in clinical prescription of testosterone in the past decade, concerns
      about the cardiovascular side-effects of androgen supplementation or androgen
      deprivation therapy are increasing. Potential atheroprotective effects of
      testosterone could be secondary to (aromatase-mediated) conversion into
      oestradiol or, alternatively, to direct activation of androgen receptors (AR).
      Recent development of animal models with cell-specific AR knockout has indicated
      a complex role for androgen action in atherosclerosis. Most studies suggest
      androgens are atheroprotective but the precise role of AR remains unclear.
      Increased use of AR knockout models should clarify the role of AR in
      atherogenesis and, thus, lead to exploitation of this pathway as a therapeutic
      target.

PMID- 29024782
TI  - Dysregulation of Delta4-3-oxosteroid 5beta-reductase in diabetic patients:
      Implications and mechanisms.
AB  - Aldo-keto reductase family 1 member D1 (AKR1D1) is a Delta4-3-oxosteroid 5beta
      reductase required for bile acid synthesis and steroid hormone metabolism. Both
      bile acids and steroid hormones, especially glucocorticoids, play important roles
      in regulating body metabolism and energy expenditure. Currently, our
      understanding on AKR1D1 regulation and its roles in metabolic diseases is
      limited. We found that AKR1D1 expression was markedly repressed in diabetic
      patients. Consistent with repressed AKR1D1 expression, hepatic bile acids were
      significantly reduced in diabetic patients. Mechanistic studies showed that
      activation of peroxisome proliferator-activated receptor-alpha (PPARalpha)
      transcriptionally down-regulated AKR1D1 expression in vitro in HepG2 cells and in
      vivo in mice. Consistently, PPARalpha signaling was enhanced in diabetic
      patients. In summary, dysregulation of AKR1D1 disrupted bile acid and steroid
      hormone homeostasis, which may contribute to the pathogenesis of diabetes.
      Restoring bile acid and steroid hormone homeostasis by modulating AKR1D1
      expression may represent a new approach to develop therapies for diabetes.

PMID- 29024783
TI  - Oxygen uptake kinetics following six weeks of interval and continuous endurance
      exercise training - An explorative pilot study.
AB  - PURPOSE: The aim of the study was to compare the responses of pulmonary (VO2pulm)
      and muscle (VO2musc) oxygen uptake kinetics before (PRE) and after (POST) six
      weeks of endurance exercise training. METHODS: Nine untrained individuals
      performed pseudo-random binary sequences work rate changes between 30W and 80W at
      PRE and POST training intervention. Heart rate (HR) and VO2pulm were measured
      beat-to-beat and breath-by-breath, respectively. VO2musc was estimated applying
      the approach of Hoffmann et al. (Eur J Appl Physiol 113: 1745-1754, 2013).
      RESULTS: Maximal oxygen uptake showed significant increases from PRE (3.2+/
      0.3Lmin-1) to POST (3.7+/-0.2Lmin-1; p<0.05). For HR, VO2pulm and VO2musc
      kinetics no significant changes from PRE to POST training intervention were
      observed (p>0.05). CONCLUSIONS: Discrepancies in the adaptations of the involved
      exercise induced physiological systems seem to be responsible for the observed
      significant alterations in maximal VO2 after six weeks of the training
      intervention in contrast to no changes in the kinetics responses.

PMID- 29024784
TI  - Causal Role of Noradrenaline in the Timing of Internally Generated Saccades in
      Monkeys.
AB  - We recently found that when monkeys performed an oculomotor version of the time
      production task, the trial-by-trial latency of self-timed saccades was negatively
      correlated with pupil diameter just before the delay period (Suzuki et al.,
      2016). Since pupil diameter has been shown to correlate with neuronal activity in
      the locus coeruleus, the level of noradrenaline (NA) in the brain might regulate
      the subjective passage of time. To examine this, we orally administered a
      selective noradrenaline reuptake inhibitor (reboxetine, 0.4-0.8 mg) when animals
      made a self-initiated memory-guided saccade >1 s following the appearance of a
      brief visual cue. We found that reboxetine delayed self-timed saccades, while the
      latency of visually triggered saccades remained unchanged. Because the changes in
      proportions and latencies of early impulsive saccades were comparable between
      conditions with and without drug administration, alteration of self-timing might
      not result from reduced impulsivity. We also assessed other behavioral parameters
      (saccade accuracy, velocity, and latency variance), but failed to find any drug
      effect except for the accuracy of visually triggered saccades in the high-dose
      condition, indicating that reboxetine specifically altered self-timing under our
      experimental conditions. Our results suggest that NA-related internal states may
      causally regulate temporal information processing in the brain.

PMID- 29024785
TI  - Slow Intrathecal Injection of rAAVrh10 Enhances its Transduction of Spinal Cord
      and Therapeutic Efficacy in a Mutant SOD1 Model of ALS.
AB  - Mutant SOD1 causes amyotrophic lateral sclerosis (ALS) by a dominant gain of
      toxicity. Previous studies have demonstrated therapeutic potential of mutant SOD1
      RNAi delivered by intrathecal (IT) injection of recombinant adeno-associated
      virus (rAAV). However, optimization of delivery is needed to overcome the high
      degree of variation in the transduction efficiency and therapeutic efficacy.
      Here, on the basis of our previously defined, efficient IT injection method, we
      investigated the influence of injection speed on transduction efficiency in the
      central nervous system (CNS). We demonstrate that slow IT injection results in
      higher transduction of spinal cord and dorsal root ganglia (DRG) while fast IT
      injection leads to higher transduction of brain and peripheral organs. To test
      how these effects influence the outcome of RNAi therapy, we used slow and fast IT
      injection to deliver rAAVrh10-GFP-amiR-SOD1, a rAAV vector that expresses GFP and
      an artificial miRNA targeting SOD1, in SOD1-G93A mice. Both slow and fast IT
      injection produced therapeutic efficacy but the slow injection trended slightly
      toward a better outcome than the fast injection. These results demonstrate that
      IT injection speed influences the predominance of gene delivery at different CNS
      sites and should be taken into consideration in future therapeutic trials
      involving IT injection.

PMID- 29024787
TI  - Ketogenic Metabolism Inhibits Histone Deacetylase (HDAC) and Reduces Oxidative
      Stress After Spinal Cord Injury in Rats.
AB  - The aim of this study is to investigate the effect of ketogenic metabolism,
      induced by different diet interventions, on histone acetylation and its potential
      antioxidant capacity to injured spinal cord tissue in rats. 72 male Sprague
      Dawley rats were randomly divided into 4 groups, fed with ketogenic diet (KD),
      every other day fasting (EODF), every other day ketogenic diet (EODKD) and
      standard diet (SD) respectively for 2 weeks. beta-Hydroxybutyrate (betaOHB)
      concentration was measured both in serum and cerebrospinal fluid (CSF). C5 spinal
      cord tissue was harvested before, at 3 h and 24 h after injury for analysis of
      HDAC activity, histone acetylation and oxidative makers. All three dietary
      interventions resulted in a significant increase of betaOHB level in both serum
      and CSF, and inhibited HDAC activity by 31-43% in spinal cord. Moreover, the
      expressions of acetylated histone AcH3K9 and AcH3K14 were significantly
      increased. Anti-oxidative stress genes Foxo3a and Mt2 and related proteins, such
      as mitochondrial superoxide dismutase (SOD), FOXO3a, catalase were increased in
      dietary intervention groups. After SCI, high ketogenic metabolism demonstrated
      significant reduction of the expression of lipid peroxidation factors
      malondialdehyde (MDA), and this might contribute to the reported neuroprotection
      of the spinal cord from oxidative damage possibly mediated by increasing SOD. The
      result of this study suggested that by inhibiting HDAC activity and modifying
      related gene transcription, ketogenic metabolism, induced by KD, EODF or EODKD,
      might reduce oxidative damage in the spinal cord tissue after acute injury.

PMID- 29024786
TI  - Neurobiological Correlates of Pain Avoidance-Like Behavior in Morphine-Dependent
      and Non-Dependent Rats.
AB  - Repeated use of opioids can lead to the development of analgesic tolerance and
      dependence. Additionally, chronic opioid exposure can cause a paradoxical
      emergence of heightened pain sensitivity to noxious stimuli, termed hyperalgesia,
      which may drive continued or escalated use of opioids to manage worsening pain
      symptoms. Opioid-induced hyperalgesia has traditionally been measured in rodents
      via reflex-based assays, including the von Frey method. To better model the
      cognitive/motivational dimension of pain in a state of opioid dependence and
      withdrawal, we employed a recently developed non-reflex-based method for
      measuring pain avoidance-like behavior in animals (mechanical conflict avoidance
      test). Adult male Wistar rats were administered an escalating dose regimen of
      morphine (opioid-dependent group) or repeated saline (control group). Morphine
      dependent rats exhibited significantly greater avoidance of noxious stimuli
      during withdrawal. We next investigated individual relationships between pain
      avoidance-like behavior and alterations in protein phosphorylation in central
      motivation-related brain areas. We discovered that pain avoidance-like behavior
      was significantly correlated with alterations in phosphorylation status of
      protein kinases (ERK, CaMKII), transcription factors (CREB), presynaptic markers
      of neurotransmitter release (Synapsin), and the rate-limiting enzyme for dopamine
      synthesis (TH) across specific brain regions. Our findings suggest that
      alterations in phosphorylation events in specific brain centers may support
      cognitive/motivational responses to avoid pain.

PMID- 29024788
TI  - Thermostability of the coating, antigen and immunostimulator in an adjuvanted
      oral capsule vaccine formulation.
AB  - Oral vaccines present an attractive alternative to injectable vaccines for
      enteric diseases due to ease of delivery and the induction of intestinal immunity
      at the site of infection. However, susceptibility to gastrointestinal
      proteolysis, limited transepithelial uptake and a lack of clinically acceptable
      adjuvants present significant challenges. A further challenge to mass vaccination
      in developing countries is the very expensive requirement to maintain the cold
      chain. We recently described the effectiveness of a Single Multiple Pill(r)
      (SmPill(r)) adjuvanted capsule approach to enhance the effectiveness of a
      candidate enterotoxigenic Escherichia coli (ETEC) oral vaccine. Here it was
      demonstrated that this delivery system maintains the antigenicity of ETEC
      colonisation factor antigen I (CFA/I) and the immunostimulatory activity of the
      orally active alpha-Galactosylceramide (alpha-GalCer) adjuvant after storage of
      SmPill(r) minispheres under room temperature and extreme storage conditions for
      several months. In addition, the internal structure of the cores of SmPill(r)
      minispheres and antigen release features at intestinal pH were found to be
      preserved under all these conditions. However, changes in the surface morphology
      of SmPill(r) minispheres leading to the antigen release at gastric pH were
      observed after a few weeks of storage under extreme conditions. Those
      modifications were prevented by the introduction of an Opadry(r) White film
      coating layer between the core of SmPill(r) minispheres and the enteric coating.
      Under these conditions, protection against antigen release at gastric pH was
      maintained even under high temperature and humidity conditions. These results
      support the potential of the SmPill(r) minisphere approach to maintain the
      stability of an adjuvanted whole cell killed oral vaccine formulation.

PMID- 29024789
TI  - In vitro pharmacological characterization of the bispyridinium non-oxime compound
      MB327 and its 2- and 3-regioisomers.
AB  - The primary toxic mechanism of organophosphorus compounds, i.e. nerve agents or
      pesticides, is based on the irreversible inhibition of acetylcholinesterase. In
      consequence of the impaired hydrolysis, the neurotransmitter acetylcholine
      accumulates in cholinergic synapses and disturbs functional activity of nicotinic
      and muscarinic acetylcholine receptors by overstimulation and subsequent
      desensitization. The resulting cholinergic syndrome will become acute life
      threatening, if not treated adequately. The current standard treatment,
      consisting of administration of a competitive mAChR antagonist (e.g. atropine)
      and an oxime (e.g. obidoxime, pralidoxime), is not sufficient in the case of
      soman or tabun intoxications. Consequently, alternative therapeutic options are
      necessary. An innovative approach comprises the use of compounds selectively
      targeting nAChRs, especially positive allosteric modulators, which increase the
      population of the conducting receptor state. MB327 (1,1'-(propane-1,3-diyl)bis(4
      tert-butylpyridinium) di(iodide)) is able to restore soman-blocked muscle-force
      in preparations of various species including human and was recently identified as
      "resensitizer". In contrast to the well-studied MB327, the pharmacological
      efficacy of the 2- and 3-tert-butylpyridinium propane regioisomers is unknown. As
      a first step, MB327 and its 3-regioisomer (PTM0001) and 2-regioisomer (PTM0002)
      were pharmacologically characterized using [3H]epibatidine binding assays,
      functional studies by solid supported membranes based electrophysiology, and in
      vitro muscle-force investigations of soman-poisoned rat hemidiaphragm
      preparations by indirect field stimulation technique. The results obtained from
      targets of different complexity (receptor, muscle tissue) showed that the
      pharmacological profiles of the 2- and 3-regioisomers were relatively similar to
      those of MB327. Furthermore, high concentrations showed inhibitory effects, which
      might critically influence the application as an antidote. Thus, more effective
      drugs have to be developed. Nevertheless, the combination of the methods
      presented is an effective tool for clarifying structure-activity relationships.

PMID- 29024790
TI  - DNA methylation and potential multigenerational epigenetic effects linked to
      uranium chronic low-dose exposure in gonads of males and females rats.
AB  - INTRODUCTION: An increased health problem in industrialised countries is the
      contemporary concern of public and scientific community as well. This has been
      attributed in part to accumulated environmental pollutants especially radioactive
      substances and the use of nuclear power plants worldwide. However, the outcome of
      chronic exposure to low doses of a radionuclide such as uranium remains unknown.
      Recently, a paradigm shift in the perception of risk of radiotoxicology has
      emerged through investigating the possibility of transmission of biological
      effects over generations, in particular by epigenetic pathways. These processes
      are known for their crucial roles associated with the development of several
      diseases. OBJECTIVE: The current work investigates the epigenetic effect of
      chronic exposure to low doses of uranium and its inheritance across generations.
      Materials and Methods To test this proposition, a rodent multigenerational model,
      males and females, were exposed to a non-toxic concentration of uranium (40mgL-1
      drinking water) for nine months. The uranium effects on were evaluated over three
      generations (F0, F1 and F2) by analysing the DNA methylation profile and DNMT
      genes expression in ovaries and testes tissues. RESULTS: Here we report a
      significant hypermethylation of testes DNA (p <0.005) whereas ovaries showed
      hypomethylated DNA (p <0.005). Interestingly, this DNA methylation profile was
      significantly maintained across generations F0, F1 and F2. Furthermore, qPCR
      results of both tissues imply a significant change in the expression of DNA
      methyltransferase genes (DNMT 1 and DNMT3a/b) as well. CONCLUSION: Altogether,
      our work demonstrates for the first time a sex-dependance and inheritance of
      epigenetic marks, DNA methylation, as a biological response to the exposure to
      low doses of uranium. However, it is not clear which type of reproductive cell
      type is more responsive in this context.

PMID- 29024791
TI  - Imaging microstructure in the living human brain: A viewpoint.
AB  - This special issue summarizes an impressive body of work concerned with in vivo
      imaging of brain microstructure. Collectively, papers included here demonstrate
      the power of multi-modal magnetic resonance imaging (MRI) for mapping various
      structural properties of brain tissue. In this introduction, I provide a user's
      perspective vis-a-vis motivations for these efforts, review briefly the cellular
      composition of grey and white matter in the human brain, and provide a few
      examples of how we can bridge the gap between ex vivo and in vivo datasets to
      facilitate interpretation of studies measuring brain macro- and microstructure.

PMID- 29024792
TI  - Effective connectivity inferred from fMRI transition dynamics during movie
      viewing points to a balanced reconfiguration of cortical interactions.
AB  - Our behavior entails a flexible and context-sensitive interplay between brain
      areas to integrate information according to goal-directed requirements. However,
      the neural mechanisms governing the entrainment of functionally specialized brain
      areas remain poorly understood. In particular, the question arises whether
      observed changes in the regional activity for different cognitive conditions are
      explained by modifications of the inputs to the brain or its connectivity? We
      observe that transitions of fMRI activity between areas convey information about
      the tasks performed by 19 subjects, watching a movie versus a black screen
      (rest). We use a model-based framework that explains this spatiotemporal
      functional connectivity pattern by the local variability for 66 cortical regions
      and the network effective connectivity between them. We find that, among the
      estimated model parameters, movie viewing affects to a larger extent the local
      activity, which we interpret as extrinsic changes related to the increased
      stimulus load. However, detailed changes in the effective connectivity preserve a
      balance in the propagating activity and select specific pathways such that high
      level brain regions integrate visual and auditory information, in particular
      boosting the communication between the two brain hemispheres. These findings
      speak to a dynamic coordination underlying the functional integration in the
      brain.

PMID- 29024794
TI  - Brain computer interface with the P300 speller: Usability for disabled people
      with amyotrophic lateral sclerosis.
AB  - OBJECTIVES: Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative
      disease, restricts patients' communication capacity a few years after onset. A
      proof-of-concept of brain-computer interface (BCI) has shown promise in ALS and
      "locked-in" patients, mostly in pre-clinical studies or with only a few patients,
      but performance was estimated not high enough to support adoption by people with
      physical limitation of speech. Here, we evaluated a visual BCI device in a
      clinical study to determine whether disabled people with multiple deficiencies
      related to ALS would be able to use BCI to communicate in a daily environment.
      METHODS: After clinical evaluation of physical, cognitive and language
      capacities, 20 patients with ALS were included. The P300 speller BCI system
      consisted of electroencephalography acquisition connected to real-time processing
      software and separate keyboard-display control software. It was equipped with
      original features such as optimal stopping of flashes and word prediction. The
      study consisted of two 3-block sessions (copy spelling, free spelling and free
      use) with the system in several modes of operation to evaluate its usability in
      terms of effectiveness, efficiency and satisfaction. RESULTS: The system was
      effective in that all participants successfully achieved all spelling tasks and
      was efficient in that 65% of participants selected more than 95% of the correct
      symbols. The mean number of correct symbols selected per minute ranged from 3.6
      (without word prediction) to 5.04 (with word prediction). Participants expressed
      satisfaction: the mean score was 8.7 on a 10-point visual analog scale assessing
      comfort, ease of use and utility. Patients quickly learned how to operate the
      system, which did not require much learning effort. CONCLUSION: With its word
      prediction and optimal stopping of flashes, which improves information transfer
      rate, the BCI system may be competitive with alternative communication systems
      such as eye-trackers. Remaining requirements to improve the device for suitable
      ergonomic use are in progress.

PMID- 29024795
TI  - Are valved holding chambers (VHCs) interchangeable? An in vitro evaluation of VHC
      equivalence.
AB  - INTRODUCTION: The European Medicines Agency (EMA) requires that a specific valved
      holding chamber (VHC) is designated for use with a given pressurised metered dose
      inhaler (pMDI). No other regulatory authorities impose similar requirements,
      implying that VHCs are interchangeable. This in vitro study, employing EMA
      assessment criteria, assessed the equivalence of four anti-static VHCs (aVHCs)
      versus the non-conducting VHC most widely referenced in pMDI monographs, the
      AeroChamber PlusTM (AC+) VHC. MATERIAL & METHODS: The "reference" AC + VHC was
      prepared by soaking in detergent solution. The four test aVHCs (AeroChamber
      PlusTM Flow-VuTM [AC + FV]; Compact Space Chamber Plus [CSC+]; InspiraChamber
      [IC]; OptiChamber DiamondTM [OCD]) were tested "out-of-packet". Twenty devices of
      each type were evaluated. A salbutamol pMDI was actuated into each VHC with a 2-s
      delay between actuation and Andersen Cascade Impactor (ACI) sampling. Drug
      deposition in four ACI particle size groups was assessed: Group 1, >5.8-10 MUm;
      Group 2, >3.3-5.8 MUm; Group 3, >1.1-3.3 MUm; Group 4, <=1.1 MUm. Equivalence
      versus the reference VHC was demonstrated where the 90% confidence interval for
      the test/reference mass ratio was within 85-118%. RESULTS: The mass retained
      within the VHC was similar for the AC + VHC and AC + FV aVHC, but was
      approximately twice as great for the other aVHCs. Salbutamol deposition in all
      ACI groups with the AC + FV aVHC was equivalent to the reference AC + VHC. By
      contrast, deposition in ACI groups 1 to 3 with the CSC+, IC and OCD aVHCs was
      inequivalent to (approximately half that of) the reference VHC. Inter-device
      variability for each VHC type was greatest for the IC and least for the AC + VHC
      and AC + FV aVHC. CONCLUSIONS: The performance of VHCs that superficially
      resemble one another may differ markedly. Thus, as implied by EMA guidelines,
      VHCs should not automatically be considered to be interchangeable.

PMID- 29024793
TI  - Sensorimotor impairment of speech auditory feedback processing in aphasia.
AB  - We investigated the brain network involved in speech sensorimotor processing by
      studying patients with post-stroke aphasia using an altered auditory feedback
      (AAF) paradigm. We combined lesion-symptom-mapping analysis and behavioral
      testing to examine the pervasiveness of speech sensorimotor deficits and their
      relationship with cortical damage. Sixteen participants with aphasia and sixteen
      neurologically intact individuals completed a speech task under AAF. The task
      involved producing speech vowel sounds under the real-time pitch-shifted auditory
      feedback alteration. This task provided an objective measure for each
      individual's ability to compensate for mismatch (error) in speech auditory
      feedback. Results indicated that compensatory speech responses to AAF were
      significantly diminished in participants with aphasia compared with control. We
      observed that within the aphasic group, subjects with lower scores on the speech
      repetition task exhibited greater degree of diminished responses. Lesion-symptom
      mapping analysis revealed that the onset phase (50-150 ms) of diminished AAF
      responses were predicted by damage to auditory cortical regions within the
      superior and middle temporal gyrus, whereas the rising phase (150-250 ms) and the
      peak (250-350 ms) of diminished AAF responses were predicted with damage to the
      inferior frontal gyrus and supramarginal gyrus areas, respectively. These
      findings suggest that damage to the auditory, motor, and auditory-motor
      integration networks are associated with impaired sensorimotor function for
      speech error processing. We suggest that a sensorimotor integration network, as
      revealed by brain regions related to temporal specific components of AAF
      responses, is related to speech processing and specific aspects of speech
      impairment, notably repetition deficits, in individuals with aphasia.

PMID- 29024796
TI  - Comparative analysis of clinics, pathologies and immune responses in BALB/c and
      C57BL/6 mice infected with Streptobacillus moniliformis.
AB  - Streptobacillus (S.) moniliformis is a rat-associated zoonotic pathogen that
      occasionally causes disease in other species. We investigated the working
      hypothesis that intranasal infection might lead to different immune responses in
      C57BL/6 and BALB/c mice associated with distinct pathologies. This study
      confirmed with 75% mortality the known high susceptibility of C57BL/6 mice to
      Streptobacillus moniliformis infection in comparison to BALB/c mice which did not
      develop signs of disease. Main pathologies in C57BL/6 mice were purulent to
      necrotizing lymphadenitis and pneumonia. Significant seroconversion was recorded
      in surviving mice of both strains. Differentiation of IgG-subclasses revealed
      mean ratios of IgG2b to IgG1 below 0.5 in sera of all mice prior to infection and
      of BALB/c mice post infection. In contrast, C57BL/6 mice had a mean IgG2b/IgG1
      ratio of 2.5 post infection indicating a Th1 immune response in C57BL/6 versus a
      Th2 response in BALB/c mice. Evaluation of different sentinel systems revealed
      that cultural and serological investigations of these animals might not be
      sufficient to detect infection. In summary, an intranasal S. moniliformis
      infection model in C57BL/6 mice leading to purulent to necrotizing inflammations
      in the lung, the lymph nodes and other organs associated with a Th1 immune
      response is described.

PMID- 29024798
TI  - Hysteroscopic Management of Asherman's Syndrome.
AB  - In developed countries Asherman's syndrome is almost always the result of a prior
      intrauterine operative trauma. This is often asymptomatic but may result in hypo-
      or amenorrhea and can contribute to infertility and pregnancy complications. We
      review their etiology, clinical implications, and systems proposed to classify
      their extent. The numerous methods reported for performing lysis of intrauterine
      adhesions are summarized along with clinical results. Current strategies to
      prevent recurrence of intrauterine adhesions have not been conclusively shown to
      be clinically effective, but the potential for endometrial regeneration using
      stem cells is an exciting modality under investigation.

PMID- 29024799
TI  - Treatment for Uterine Isthmocele, A Pouchlike Defect at the Site of a Cesarean
      Section Scar.
AB  - An isthmocele appears as a fluid pouchlike defect in the anterior uterine wall at
      the site of a prior cesarean section and ranges in prevalence from 19% to 84%, a
      direct relation to the increase in cesarean sections performed worldwide. Many
      definitions have been suggested for the dehiscence resulting from cesarean
      sections, and we propose standardization with a single term for all cases
      isthmocele. Patients are not always symptomatic, but symptoms typically include
      intermittent abnormal bleeding, pain, and infertility. Pregnancy complications
      that result from an isthmocele include ectopic pregnancy, low implantation, and
      uterine rupture. Magnetic resonance imaging and transvaginal ultrasound are the
      gold standard imaging techniques for diagnosis. Surgical treatment of an
      isthmocele is still a controversial issue but should be offered to symptomatic
      women or the asymptomatic patient who desires future pregnancy. When surgery is
      the treatment choice, laparoscopy guided by hysteroscopy, hysteroscopy alone, or
      vaginal repair are the best options depending on the isthmocele's characteristics
      and surgeon expertise.

PMID- 29024797
TI  - NLRX1 modulates differentially NLRP3 inflammasome activation and NF-kappaB
      signaling during Fusobacterium nucleatum infection.
AB  - NOD-like receptors (NLRs) play a large role in regulation of host innate
      immunity, yet their role in periodontitis remains to be defined. NLRX1, a member
      of the NLR family that localizes to mitochondria, enhances mitochondrial ROS
      (mROS) generation. mROS can activate the NLRP3 inflammasome, yet the role of
      NLRX1 in NLRP3 inflammasome activation has not been examined. In this study, we
      revealed the mechanism by which NLRX1 positively regulates ATP-induced NLRP3
      inflammasome activation through mROS in gingival epithelial cells (GECs). We
      found that depletion of NLRX1 by shRNA attenuated ATP-induced mROS generation and
      redistribution of the NLRP3 inflammasome adaptor protein, ASC. Furthermore,
      depletion of NLRX1 inhibited Fusobacterium nucleatum infection-activated caspase
      1, suggesting that it also inhibits the NLRP3 inflammasome. Conversely, NLRX1
      also acted as a negative regulator of NF-kappaB signaling and IL-8 expression.
      Thus, NLRX1 stimulates detection of the pathogen F. nucleatum via the
      inflammasome, while dampening cytokine production. We expect that commensals
      should not activate the inflammasome, and NLRX1 should decrease their ability to
      stimulate expression of pro-inflammatory cytokines such as IL-8. Therefore, NLRX1
      may act as a potential switch with regards to anti-microbial responses in healthy
      or diseased states in the oral cavity.

PMID- 29024800
TI  - Transvaginal Resection of an Infected Sacrocolpopexy Mesh by Single-Port Trocar.
AB  - STUDY OBJECTIVE: Laparoscopy using a single port improves morbidity while keeping
      the same level of requirement. This technique has been evaluated in gynecology
      for salpingectomy, ovarian surgery, and hysterectomy. Here, the authors
      illustrate a new use of a single port using the transvaginal approach. DESIGN:
      Case report (Canadian Task Force classification III). SETTING: Tertiary referral
      center in Strasbourg, France. PATIENT: Woman age 59 years. INTERVENTION: Single
      port platform used in the transvaginal approach for resection of sacrocolpopexy
      mesh. The local institutional review board approved the video. MEASUREMENTS AND
      MAIN RESULTS: A 59-year-old woman suffering from insulin-dependent diabetes and a
      tobacco user had 2 laparoscopic sacrocolpopexies for recurrent rectocele, the
      first in 2007 and the second in 2012. The sequences were marked by mesh erosion
      and granuloma in the vagina, requiring its surgical excision in 2016. The patient
      was then symptomatic, with an increasingly foul-smelling vaginal discharge with
      recurrent mesh erosion. Magnetic resonance imaging showed an abscess formation
      along the length of the mesh to the promontory. The patient then underwent
      surgery, realized under probabilistic antibiotic therapy, consisting of complete
      excision of the sacrocolpopexy mesh by the transvaginal approach. After putting
      the single-port trocar (GelPoint; Applied Medical, Rancho Santa Margarita, CA)
      into the vagina and obtaining distension with the insufflator (AirSeal; Conmed,
      Utica, NY), classic laparoscopic instruments were introduced by the single-port
      trocar. The mesh was entirely resected in the retroperitoneal space. Mesh was
      again used because the exposed space is almost always surrounded by loose
      granulation tissue that facilitates dissection and also prevents injury to
      adjacent structures such as bladder, rectum, and peritoneum. Moreover, the
      opening of adjacent structures will manifest gas leaks and, consequently, loss of
      the pneumovagina. At the end of procedure, the vagina is not closed to permit
      optimal drainage with a multitubular drain in the dissection space. The surgery
      lasted 60 minutes. The mesh excision was completed with relative ease, and there
      was no blood loss. Bacteriologic examination revealed the presence of
      Streptococcus anginosus, Klebsiella pneumoniae, and Bacteroides fragili. The
      operating suites were simple with great cicatrization after 6 weeks. The
      principal difficulties of this surgery were obtaining a good seal by the creation
      of cutaneous sutures. Finally, there are less conflicts between the instruments
      inside the single-port trocar used in transvaginally because of a more limited
      dissection space. Indeed, the rate of mesh erosion reached 2.4% and, in case of
      infection, justifies this excision. CONCLUSION: The transvaginal use of a single
      port trocar represents a good alternative, allowing easy resection of the
      sacrocolpopexy mesh while remaining in the retroperitoneal space.

PMID- 29024802
TI  - Synovial and systemic pharmacokinetics (PK) of triamcinolone acetonide (TA)
      following intra-articular (IA) injection of an extended-release microsphere-based
      formulation (FX006) or standard crystalline suspension in patients with knee
      osteoarthritis (OA).
AB  - OBJECTIVE: Intra-articular (IA) corticosteroids relieve osteoarthritis (OA) pain,
      but rapid absorption into systemic circulation may limit efficacy and produce
      untoward effects. We compared the pharmacokinetics (PK) of IA triamcinolone
      acetonide (TA) delivered as an extended-release, microsphere-based formulation
      (FX006) vs a crystalline suspension (TAcs) in knee OA patients. METHOD: This
      Phase 2 open-label study sequentially enrolled 81 patients who received a single
      IA injection of FX006 (5 mL, 32 mg delivered dose, N = 63) or TAcs (1 mL, 40 mg,
      N = 18). Synovial fluid (SF) aspiration was attempted in each patient at baseline
      and one post-IA-injection visit (FX006: Week 1, Week 6, Week 12, Week 16 or Week
      20; TAcs: Week 6). Blood was collected at baseline and multiple post-injection
      times. TA concentrations (validated LC-MS/MS, geometric means (GMs)), PK (non
      compartmental analysis models), and adverse events (AEs) were assessed. RESULTS:
      SF TA concentrations following FX006 were quantifiable through Week 12 (pg/mL:
      231,328.9 at Week 1; 3590.0 at Week 6; 290.6 at Week 12); post-TAcs, only two of
      eight patients had quantifiable SF TA at Week 6 (7.7 pg/mL). Following FX006,
      plasma TA gradually increased to peak (836.4 pg/mL) over 24 h and slowly declined
      to <110 pg/mL over Weeks 12-20; following TAcs, plasma TA peaked at 4 h (9628.8
      pg/mL), decreased to 4991.1 pg/mL at 24 h, and was 149.4 pg/mL at Week 6, the
      last post-treatment time point assessed. AEs were similar between groups.
      CONCLUSION: In knee OA patients, microsphere-based TA delivery via a single IA
      injection prolonged SF joint residency, diminished peak plasma levels, and thus
      reduced systemic TA exposure relative to TAcs.

PMID- 29024801
TI  - Population-based prevalence of multiple radiographically-defined hip
      morphologies: the Johnston County Osteoarthritis Project.
AB  - OBJECTIVE: To provide the first prevalence estimates of different radiographic
      hip morphologies relevant to dysplasia and femoroacetabular impingement in a well
      characterized USA population-based cohort. METHODS: Cross-sectional data were
      from the baseline examination (1991-1997) of a large population-based prospective
      longitudinal cohort study (The Johnston County Osteoarthritis Project). HipMorf
      software (Oxford, UK) was used to assess hip morphology on anteroposterior (AP)
      pelvis radiographs. Weighted, sex-stratified prevalence estimates and 95%
      confidence intervals for four key hip morphologies (AP alpha angle, triangular
      index sign, lateral center edge angle (LCEA), and protrusio acetabula) were
      derived and further stratified by age, race and body mass index (BMI). RESULTS: A
      total of 5192 hips from 2596 individuals were included (31% African American, 43%
      male, mean age 63 years, mean BMI 29 kg/m2). Cam morphology was seen in more than
      25% of men and 10% of women. Mild dysplasia was present in about 1/3 of men and
      women, while pincer morphology was identified in 7% of men and 10% of women.
      Femoral side (cam) morphologies were more common and more frequently bilateral
      among men, while pincer morphologies were more common in women; mixed
      morphologies were infrequent. African-Americans were more likely to have
      protrusio acetabula than whites. CONCLUSION: We report the first population-based
      prevalence estimates of radiographic hip morphologies relevant to
      femoroacetabular impingement (FAI) and dysplasia in the USA. These morphologies
      are very common, with 1/4 men and 1/10 women having cam morphology, 1/3 of all
      adults having mild dysplasia, and 1/15 men and 1/10 women having pincer
      morphology in at least one hip.

PMID- 29024803
TI  - Graft-Derived Reconstitution of Mucosal-Associated Invariant T Cells after
      Allogeneic Hematopoietic Cell Transplantation.
AB  - Mucosal-associated invariant T (MAIT) cells express a semi-invariant Valpha7.2+ T
      cell receptor (TCR) that recognizes ligands from distinct bacterial and fungal
      species. In neonates, MAIT cells proliferate coincident with gastrointestinal
      (GI) bacterial colonization. In contrast, under noninflammatory conditions adult
      MAIT cells remain quiescent because of acquired regulation of TCR signaling.
      Effects of inflammation and the altered GI microbiota after allogeneic
      hematopoietic cell transplantation (HCT) on MAIT cell reconstitution have not
      been described. We conducted an observational study of MAIT cell reconstitution
      in myeloablative (n = 41) and nonmyeloablative (n = 66) allogeneic HCT recipients
      and found that despite a rapid and early increase to a plateau at day 30 after
      HCT, MAIT cell numbers failed to normalize for at least 1 year. Cord blood
      transplant recipients and those who received post-HCT cyclophosphamide for graft
      versus host disease (GVHD) prophylaxis had profoundly impaired MAIT cell
      reconstitution. Sharing of TCRbeta gene sequences between MAIT cells isolated
      from HCT grafts and blood of recipients after HCT showed early MAIT cell
      reconstitution was due at least in part to proliferation of MAIT cells
      transferred in the HCT graft. Inflammatory cytokines were required for TCR
      dependent MAIT cell proliferation, suggesting that bacterial Valpha7.2+ TCR
      ligands might promote MAIT cell reconstitution after HCT. Robust MAIT cell
      reconstitution was associated with an increased GI abundance of Blautia spp. MAIT
      cells suppressed proliferation of conventional T cells consistent with a possible
      regulatory role. Our data identify modifiable factors impacting MAIT cell
      reconstitution that could influence the risk of GVHD after HCT.

PMID- 29024804
TI  - Impact of HLA Disparity in Haploidentical Bone Marrow Transplantation Followed by
      High-Dose Cyclophosphamide.
AB  - We studied the impact of HLA mismatching on the outcome of 318 consecutive
      patients who received an unmanipulated haploidentical bone marrow transplant,
      followed by post-transplant cyclophosphamide (PTCy). The number of HLA-mismatched
      antigens was tested for its impact on overall survival (OS) and nonrelapse
      mortality (NRM), whereas HLA mismatches in the graft-versus-host (GVH) direction
      were tested for prediction of graft-versus-host disease (GVHD and relapse.
      Finally, we studied whether graft rejection correlated with the number of HLA
      mismatched antigens in host-versus-graft (HVG) direction. Two hundred thirty-one
      donor-recipient pairs (72%) had 4/8 mismatches at the -A, -B, -C, -DRB1 HLA loci.
      HLA mismatches did not predict the 2-year OS (hazard ratio, .83; P = .58) and NRM
      (subhazard ratio, 1.08; P = .93). The cumulative incidence of acute GVHD (P =
      .13), 1-year chronic GVHD (P = .84), and relapse rate (P = .26) did not correlate
      with univectorial GVH mismatches. Similarly, no correlation was observed between
      the amount of HLA mismatch in the HVG direction and graft rejection. In
      multivariate analysis advanced disease at transplant was the strongest predictor
      of survival, NRM, relapse, and graft rejection. In conclusion, the degree of HLA
      mismatching should not be used as a criterion to select family haploidentical
      donors when using bone marrow as stem cell source and PTCy for GVHD prophylaxis.

PMID- 29024805
TI  - Demonstrating significant benefit of orphan medicines: analysis of 15 years of
      experience in Europe.
AB  - In the European Union demonstration of 'significant benefit' is mandatory if
      satisfactory methods exist for a disease targeted by a new orphan medicinal
      product. Significant benefit is required at the time of orphan designation, when
      it can be supported by preclinical studies, and at the time of marketing
      authorization, when clinical data are needed. For the first time, our work has
      identified, defined and organized the scientific grounds on which significant
      benefit is granted in the European Union, based on a review of the orphan
      medicinal products authorized in the years 2000-2015, and on the working
      experience of the Committee of Orphan Medicinal Products. The resulting
      conceptual framework is a tool for medicine developers to reflect on potential
      areas of advantage of their candidate products, and for a broad range of
      stakeholders to stimulate the discussion on the added value of orphan medicines
      across the whole development lifecycle.

PMID- 29024806
TI  - Dimerization and oxidation of tryptophan in UV-A photolysis sensitized by
      kynurenic acid.
AB  - Photoinduced generation of radicals in the eye lens may play an important role in
      the modification of proteins leading to their coloration, aggregation, and
      insolubilization. The radicals can be formed via the reactions of photoexcited
      endogenous chromophores of the human lens with lens proteins, in particular with
      tryptophan residues. In the present work we studied the reactions induced by UV-A
      (315-400nm) light between kynurenic acid (KNA), an effective photosensitizer
      present in the human lens, and N-acetyl-L-tryptophan (NTrpH) under aerobic and
      anaerobic conditions. Our results show that the reaction mechanism strongly
      depends on the presence of oxygen in solution. Under aerobic conditions, the
      generation of singlet oxygen is the major channel of the effective NTrpH
      oxidation. In argon-bubbled solutions, the quenching of triplet KNA by NTrpH
      results in the formation of KNA*- and NTrp* radicals. Under laser pulse
      irradiation, when the radical concentration is high, the main pathway of the
      radical decay is the back electron transfer with the restoration of initial
      reagents. Other reactions include (i) the radical combination yielding NTrp
      dimers and (ii) the oxygen atom transfer from KNA*- to NTrp* with the formation
      of oxidized NTrp species and deoxygenated KNA products. In continuous-wave
      photolysis, even trace amounts of molecular oxygen are sufficient to oxidize the
      majority of KNA*- radicals with the rate constant of (2.0 +/- 0.2) * 109M-1s-1,
      leading to the restoration of KNA and the formation of superoxide radical O2*-.
      The latter reacts with NTrp* via either the radical combination to form oxidized
      NTrp (minor pathway), or the electron transfer to restore NTrpH in the ground
      state (major pathway). As the result, the quantum yields of the starting compound
      decomposition under continuous-wave anaerobic photolysis are rather low: 1.6% for
      NTrpH and 0.02% for KNA. The photolysis of KNA with alpha-crystallin yields the
      same deoxygenated KNA products as the photolysis of KNA with NTrpH, indicating
      the similarity of the photolysis mechanisms. Thus, inside the eye lens KNA can
      sensitize both protein photooxidation and protein covalent cross-linking with the
      minor self-degradation. This may play an important role in the lens protein
      modifications during the normal aging and cataract development.

PMID- 29024807
TI  - Reactive oxygen species enhance mitochondrial function, insulin sensitivity and
      glucose uptake in skeletal muscle of senescence accelerated prone mice SAMP8.
AB  - Whereas reactive oxygen species (ROS) can have opposite impacts on insulin
      signaling, they have mainly been associated with mitochondrial dysfunction in
      skeletal muscle. We analyzed the relationship between these three features in
      skeletal muscle of senescence accelerated mice (SAM) prone (P8), which are
      characterized by enhanced oxidative stress compared to SAM resistant (R1).
      Oxidative stress, ROS production, antioxidant system, mitochondrial content and
      functioning, as well as in vitro and in vivo insulin signaling were investigated
      in gastrocnemius and quadriceps muscles. In SAMP8 compared to SAMR1, muscle
      content in carbonylated proteins was two-fold (p < 0.01) and ROS production by
      xanthine oxidase 70% (p < 0.05) higher. Furthermore, insulin-induced Akt
      phosphorylation measured in vivo and ex vivo as well as muscle glucose uptake
      measured ex vivo were significantly higher (p < 0.05). Mitochondrial respiration
      evidenced uncoupling and higher respiration rates with substrates of complexes II
      and IV, in agreement with higher maximal activity of complexes II and IV (+ 18%
      and 62%, respectively, p < 0.05). By contrast, maximal activity of complex I was
      22% lower (p < 0.05). All strain differences were corrected after 6 months of N
      acetylcysteine (NAC) treatment, thus supporting the involvement of high ROS
      production in these differences. In conclusion in muscle of SAMP8 compared to
      SAMR1, high ROS production is associated to higher insulin sensitivity and
      glucose uptake but to lower mitochondrial complex I activity. These conflicting
      adaptations, with regards to the resulting imbalance between NADH production and
      use, were associated with intrinsic adjustments in the mitochondrial respiration
      chain (mitochondrial uncoupling, enhanced complexes II and IV activity). We
      propose that these bioenergetics adaptations may help at preserving muscle
      metabolic flexibility of SAMP8.

PMID- 29024808
TI  - Critical care nurses' experiences of withdrawal of treatment: A systematic review
      of qualitative evidence.
AB  - BACKGROUND: Death and dying is a reality of the clinical context of the intensive
      care unit. Death often follows a decision to withdraw life-sustaining treatments.
      Critical care nurses, are the primary care providers to patients and families at
      the end-of-life in the intensive care unit. OBJECTIVE: To synthesize qualitative
      evidence on the experiences of critical care nurses who have cared for patients
      and families throughout the process of withdrawal of life-sustaining treatment.
      METHODS: This was a systematic review and qualitative evidence synthesis modeled
      on the Joanna Briggs Methodology. Pre-defined keywords were searched for in
      Medline, CINAHL, PsycInfo, and Web of Science to locate studies published in the
      English, French, and Greek languages in any year. Two reviewers independently
      screened articles for congruence with eligibility criteria, engaged in data
      extraction, and assessed quality of the included studies. Meta-aggregation was
      performed to synthesize the findings. A protocol was developed by two members of
      the review team prior to initiation of the study. RESULTS: Thirteen studies were
      included in the review, 12 qualitative and one mixed-methods. Four key themes
      were identified from the original research: Navigating Complexity and Conflict;
      Focusing on the Patient; Working with Families; and Dealing with Emotions Related
      to Treatment Withdrawal. Critical care nurses provide care to patients and
      families during the process of withdrawal of life-sustaining treatment which is
      described as complex and challenging. Despite the inherent challenges, nurses
      strive towards doing their utmost for patients and families.

PMID- 29024809
TI  - Towards a more complex perspective on workplace violence: More to come?
      Commentary on Zhang et al., 2017 "Workplace violence against nurses: A cross
      sectional study".

PMID- 29024810
TI  - MAGEA6 promotes human glioma cell survival via targeting AMPKalpha1.
AB  - Melanoma antigen A6 (MAGEA6)/TRIM28 complex is a cancer-specific ubiquitin
      ligase, which degradates tumor suppressor protein AMP-activated protein kinase
      (AMPK). We show that MAGEA6 is uniquely expressed in human glioma tissues and
      cells, which is correlated with AMPKalpha1 downregulation. It is yet absent in
      normal brain tissues and human astrocytes/neuronal cells. MAGEA6 knockdown by
      targeted-shRNA in glioma cells restored AMPKalpha1 expression, causing mTORC1 in
      activation and cell death/apoptosis. Reversely, AMPKalpha1 knockdown or mutation
      ameliorated glioma cell death by MAGEA6 shRNA. In vivo, Glioma xenograft tumor
      growth in mice was largely inhibited following expressing MAGEA6 shRNA.
      AMPKalpha1 upregulation and mTORC1 inhibition were observed in MAGEA6 shRNA
      bearing xenograft tissues. Collectively, MAGEA6 promotes glioma cell survival
      possibly via targeting AMPKalpha1.

PMID- 29024811
TI  - CNOT2 promotes proliferation and angiogenesis via VEGF signaling in MDA-MB-231
      breast cancer cells.
AB  - Here the underlying role of CNOT2, a subunit of CCR4-NOT complex, was elucidated
      in cancer progression. CNOT2 was overexpressed in HIT-T15, ASPC-1, BXPC-3, PC-3,
      LNCaP, MCF-7 and MDA-MB-231 cell lines, which was confirmed by Tissue array in
      various human tumor tissues. Also, CNOT2 depletion suppressed proliferation and
      colony formation of MDA-MB-231 cells. Of note, microarray revealed decreased
      expression of CNOT2, VEGF-A, HIF2 alpha (<0.5 fold) and increased expression of
      UMOD1, LOC727847, MMP4, hCG and other genes (>2.0 fold) in CNOT2 depleted MDA-MB
      231 cells compared to untreated control. Consistently, downregulation of VEGF,
      CNOT2 and HIF2 alpha was verified in CNOT2 depleted MDA-MB-231 cells by RT-qPCR.
      Additionally, CNOT2 depletion inhibited VEGF induced tube formation in HUVECs and
      reduced neovascularization in CAM assay. Furthermore, the growth of CNOT2
      depleted MDA-MB-231 cells was significantly reduced in Balb/c nude mice along
      with decreased expression of VEGF and PCNA by immunohistochemistry compared to
      untreated control group. Overall, our findings provide evidences that CNOT2
      promotes proliferation and angiogenesis via VEGF signaling in MDA-MB-231 breast
      cancer cells as a potent molecular target for breast cancer treatment.

PMID- 29024812
TI  - Inhibition of pyruvate carboxylase by 1alpha,25-dihydroxyvitamin D promotes
      oxidative stress in early breast cancer progression.
AB  - Maintaining reductive-oxidative (redox) balance is an essential feature in breast
      cancer cell survival, with cellular metabolism playing an integral role in
      maintaining redox balance through its supply of reduced NADPH. In the present
      studies, the effect of 1,25-dihydroxyvitamin D (1,25(OH)2D) on redox balance was
      investigated in early stages of breast cancer. Treatment with 1,25(OH)2D promoted
      oxidative stress in MCF10A-ras and MCF10A-ErbB2 breast epithelial cells, as
      measured by the decreased ratios of NADPH/NADP+ and reduced to oxidized
      glutathione (GSH/GSSG). The mRNA and protein expression of the enzyme pyruvate
      carboxylase (PC) was downregulated with 1,25(OH)2D treatment, suggesting a
      potential mechanism. Genetic depletion of PC in MCF10A-ras cells resulted in a
      decreased ratio of NADPH/NADP+ and GSH/GSSG, with 1,25(OH)2D treatment having no
      further effect. Mutation analysis confirmed the presence and functionality of a
      vitamin D response element in the PC gene promoter region. Collectively, these
      results provide evidence that 1,25(OH)2D promotes oxidative stress in early
      breast cancer progression through transcriptional downregulation of PC.

PMID- 29024813
TI  - A prodrug of green tea polyphenol (-)-epigallocatechin-3-gallate (Pro-EGCG)
      serves as a novel angiogenesis inhibitor in endometrial cancer.
AB  - Anti-angiogenesis effect of a prodrug of green tea polyphenol (-)
      epigallocatechin-3-gallate (Pro-EGCG) in malignant tumors is not well studied.
      Here, we investigated how the treatment with Pro-EGCG inhibited tumor
      angiogenesis in endometrial cancer. Tumor xenografts of human endometrial cancer
      were established and subjected to microarray analysis after Pro-EGCG treatment.
      First, we showed Pro-EGCG inhibited tumor angiogenesis in xenograft models
      through down-regulation of vascular endothelial growth factor A (VEGFA) and
      hypoxia inducible factor 1 alpha (HIF1alpha) in tumor cells and chemokine (C-X-C
      motif) ligand 12 (CXCL12) in host stroma by immunohistochemical staining. Next,
      we investigated how HIF1alpha/VEGFA was down-regulated and how the reduction of
      CXCL12 inhibited tumor angiogenesis. We found that VEGFA secretion from
      endometrial cancer cells was decreased by Pro-EGCG treatment through inhibiting
      PI3K/AKT/mTOR/HIF1alpha pathway. Furthermore, the down-regulation of CXCL12 in
      stromal cells by Pro-EGCG treatment restricted migration and differentiation of
      macrophages thereby inhibited infiltration of VEGFA-expressing tumor-associated
      macrophages (TAMs). Taken together, we demonstrated that treatment with Pro-EGCG
      not only decreases cancer cell-secreted VEGFA but also inhibits TAM-secreted
      VEGFA in endometrial cancer. These findings demonstrate that Pro-EGCG is a novel
      angiogenesis inhibitor for endometrial cancer.

PMID- 29024814
TI  - Anti-tumor effects of NVP-BKM120 alone or in combination with MEK162 in biliary
      tract cancer.
AB  - There are currently no clinically validated therapeutic targets for biliary tract
      cancer (BTC). Despite promising results in other cancers, compounds targeting the
      phosphatidylinositol 3-kinase (PI3K)/AKT pathway, alone or in combination with
      Ras/Raf/MEK pathway inhibitors, have not been evaluated in BTC. Here, we examined
      the effects of a pan-PI3K inhibitor (BKM120) with or without a MEK inhibitor
      (MEK162), on eight human BTC cell lines carrying mutations in K-Ras and/or the
      PI3K catalytic subunit, PI3KCA. BKM120 inhibited the colony-forming ability and
      migration of BTC cells carrying wild-type (WT) PI3KCA and either mutant (MT) or
      WT K-Ras, but not of cells carrying mutations in both genes. In K-Ras-WT cells,
      BKM120 decreased the phosphorylation of Akt, its downstream effector kinase
      p70S6K, and the translational repressor 4E-BP1. Interestingly, BKM120 did not
      induce cell cycle arrest or suppress PI3K signaling via restoration of p-4E-BP1
      in cells with PIK3CA and K-Ras double mutations. Notably, the resistance of dual
      K-Ras/PI3KCA-mutant cells to BKM120 was overcome by treatment with a combination
      of BKM120 and MEK162. Our findings thus support the clinical development of
      BKM120 monotherapy or BKM120/MEK162 combination therapy for the treatment of BTC.

PMID- 29024815
TI  - Identification of a novel autophagic inhibitor cepharanthine to enhance the anti
      cancer property of dacomitinib in non-small cell lung cancer.
AB  - Inhibition of autophagy is a promising strategy for non-small cell lung cancer
      (NSCLC) treatment, which is in the clinical trials. However, only chloroquine is
      used in clinic as an autophagic inhibitor and the inhibitory effect of
      chloroquine on autophagy is finite. Therefore, the development of an alternative
      autophagic inhibitor for NSCLC therapy becomes necessary. In the present study,
      cepharanthine (CEP), an alkaloid extracted from Stephania cepharantha Hayata, was
      identified as a novel autophagic inhibitor in NSCLC cells. The potential
      mechanism of the CEP-inhibited autophagy was by blockage of autophagosome
      lysosome fusion and inhibition of lysosomal cathepsin B and cathepsin D
      maturation. Furthermore, we found for the first time that dacomitinib (DAC), a
      second-generation epidermal growth factor receptor inhibitor that in the phase
      III clinical trials for NSCLC treatment, induced a protective autophagy to
      decrease its anti-cancer effect. Combined treatment with CEP increased the anti
      proliferative and apoptotic effects of DAC in vitro and enhanced the anti-cancer
      effect of DAC in NCI-H1975 xenograft mice. Collectively, CEP might be further
      developed as an autophagic inhibitor, and combined treatment of CEP and DAC could
      offer an effective strategy for NSCLC treatment.

PMID- 29024816
TI  - Radiation, radionuclides and bacteria: An in-perspective review.
AB  - There has been a significant surge in consumption of radionuclides for various
      academic and commercial purposes. Correspondingly, there has been a considerable
      amount of generation of radioactive waste. Bacteria and archaea, being earliest
      inhabitants on earth serve as model microorganisms on earth. These microbes have
      consistently proven their mettle by surviving extreme environments, even extreme
      ionizing radiations. Their ability to accept and undergo stable genetic mutations
      have led to development of recombinant mutants that are been exploited for
      remediation of various pollutants such as; heavy metals, hydrocarbons and even
      radioactive waste (radwaste). Thus, microbes have repeatedly presented themselves
      to be prime candidates suitable for remediation of radwaste. It is interesting to
      study the behind-the-scenes interactions these microbes possess when observed in
      presence of radionuclides. The emphasis is on the indigenous bacteria isolated
      from radionuclide containing environments as well as the five fundamental
      interaction mechanisms that have been studied extensively, namely;
      bioaccumulation, biotransformation, biosorption, biosolubilisation and
      bioprecipitation. Application of microbes exhibiting such mechanisms in
      remediation of radioactive waste depends largely on the individual capability of
      the species. Challenges pertaining to its potential bioremediation activity is
      also been briefly discussed. This review provides an insight into the various
      mechanisms bacteria uses to tolerate, survive and carry out processes that could
      potentially lead the eco-friendly approach for removal of radionuclides.

PMID- 29024817
TI  - Oceanic dispersion of Fukushima-derived Cs-137 simulated by multiple oceanic
      general circulation models.
AB  - To understand the concentration and amount of Fukushima-derived Cs-137 in the
      ocean, this study simulated the oceanic dispersion of Cs-137 by atmospheric and
      oceanic dispersion simulations. The oceanic dispersion simulations were carried
      out with an oceanic dispersion model and multiple oceanic general circulation
      models. The Cs-137 concentrations were sensitive to ocean currents in the
      coastal, offshore, and open oceans. The mean Cs-137 concentrations of the
      multiple models relatively well agreed with the observed concentrations in the
      coastal and offshore oceans during the first few months after the Fukushima
      disaster, and in the open ocean during the first year after the disaster. The Cs
      137 amounts were quantified in the coastal, offshore, and open oceans during the
      first year after the disaster. It was suggested that Cs-137 actively dispersed
      from the coastal and offshore oceans to the open ocean, and from the surface
      layer to the deeper layers in the North Pacific.

PMID- 29024818
TI  - Differential cortical contribution of syntax and semantics: An fMRI study on two
      word phrasal processing.
AB  - Linguistic expressions consist of sequences of words combined together to form
      phrases and sentences. The neurocognitive process handling word combination is
      drawing increasing attention among the neuroscientific community, given that the
      underlying syntactic and semantic mechanisms of such basic combinations-although
      essential to the generation of more complex structures-still need to be
      consistently determined. The current experiment was conducted to disentangle the
      neural networks supporting syntactic and semantic processing at the level of two
      word combinations. We manipulated the combinatorial load by using words of
      different grammatical classes within the phrase, such that determiner-noun
      combinations (this ship) were used to boost neural activity in syntax-related
      areas, while adjective-noun combinations (blue ship) were conversely used to
      measure neural response in semantic-related combinations. By means of functional
      magnetic resonance imaging (fMRI), we found that syntax-related processing mainly
      activates the most ventral part of the inferior frontal gyrus (IFG), along the
      frontal operculum (FOP) and anterior insula (aINS). Fine-grained analysis in BA44
      confirmed that the most inferior-ventral portion is highly sensitive to syntactic
      computations driven by function words. Semantic-related processing on the
      contrary, rather engages the anterior dorsal part of the left IFG and the left
      angular gyrus (AG) that is two regions which appear to perform different
      functions within the semantic network. Our findings suggest that syntactic and
      semantic contribution to phrasal formation can be already differentiated at a
      very basic level, with each of these two processes comprising non-overlapping
      areas on the cerebral cortex. Specifically, they confirm the role of the ventral
      IFG for the construction of syntactically legal linguistic constructions, and the
      prominence of the more anterior IFG and the AG for conceptual semantics.

PMID- 29024819
TI  - A modular metabolic engineering approach for the production of 1,2-propanediol
      from glycerol by Saccharomyces cerevisiae.
AB  - Compared to sugars, a major advantage of using glycerol as a feedstock for
      industrial bioprocesses is the fact that this molecule is more reduced than
      sugars. A compound whose biotechnological production might greatly profit from
      the substrate's higher reducing power is 1,2-propanediol (1,2-PDO). Here we
      present a novel metabolic engineering approach to produce 1,2-PDO from glycerol
      in S. cerevisiae. Apart from implementing the heterologous methylglyoxal (MG)
      pathway for 1,2-PDO formation from dihydroxyacetone phosphate (DHAP) and
      expressing a heterologous glycerol facilitator, the employed genetic
      modifications included the replacement of the native FAD-dependent glycerol
      catabolic pathway by the 'DHA pathway' for delivery of cytosolic NADH and the
      reduction of triosephosphate isomerase (TPI) activity for increased precursor
      (DHAP) supply. The choice of the medium had a crucial impact on both the strength
      of the metabolic switch towards fermentation in general (as indicated by the
      production of ethanol and 1,2-PDO) and on the ratio at which these two
      fermentation products were formed. For example, virtually no 1,2-PDO but only
      ethanol was formed in synthetic glycerol medium with urea as the nitrogen source.
      When nutrient-limited complex YG medium was used, significant amounts of 1,2-PDO
      were formed and it became obvious that the concerted supply of NADH and DHAP are
      essential for boosting 1,2-PDO production. Additionally, optimizing the flux into
      the MG pathway improved 1,2-PDO formation at the expense of ethanol. Cultivation
      of the best-performing strain in YG medium and a controlled bioreactor set-up
      resulted in a maximum titer of > 4gL-1 1,2-PDO which, to the best of our
      knowledge, has been the highest titer of 1,2-PDO obtained in yeast so far.
      Surprisingly, significant 1,2-PDO production was also obtained in synthetic
      glycerol medium after changing the nitrogen source towards ammonium sulfate and
      adding a buffer.

PMID- 29024820
TI  - Coating of silicone with mannoside-PAMAM dendrimers to enhance formation of non
      pathogenic Escherichia coli biofilms against colonization of uropathogens.
AB  - : Bacterial interference using non-pathogenic Escherichia coli 83972 is a novel
      strategy for preventing catheter-associated urinary tract infection (CAUTI).
      Crucial to the success of this strategy is to establish a high coverage and
      stable biofilm of the non-pathogenic bacteria on the catheter surface. However,
      this non-pathogenic strain is sluggish to form biofilms on silicone as the most
      widely used material for urinary catheters. We have addressed this issue by
      modifying the silicone catheter surfaces with mannosides that promote the biofilm
      formation, but the stability of the non-pathogenic biofilms challenged by
      uropathogens over long-term remains a concern. Herein, we report our study on the
      stability of the non-pathogenic biofilms grown on propynylphenyl mannoside
      modified silicone. The result shows that 94% non-pathogenic bacteria were
      retained on the modified silicone under >0.5 Pa shear stress. After being
      challenged by three multidrug-resistant uropathogenic isolates in artificial
      urine for 11 days, large amounts (>4 * 106 CFU cm-2) of the non-pathogenic
      bacteria remained on the surfaces. These non-pathogenic biofilms reduced the
      colonization of the uropathogens by >3.2-log. STATEMENT OF SIGNIFICANCE: In
      bacterial interference, the non-pathogenic Escherichia coli strains are sluggish
      to form biofilms on the catheter surfaces, due to rapid removal by urine flow. We
      have demonstrated a solution to this bottleneck by pre-functionalization of
      mannosides on the silicone surfaces to promote E. coli biofilm formation. A pre
      conjugated high affinity propynylphenyl mannoside ligand tethered to the
      nanometric amino-terminated poly(amido amine) (PAMAM) dendrimer is used for
      binding to a major E. coli adhesin FimH. It greatly improves the efficiency for
      the catheter modification, the non-pathogenic biofilm coverage, as well as the
      (long-term) stability for prevention of uropathogen infections.

PMID- 29024821
TI  - Improving the efficiency of psychological treatment using outcome feedback
      technology.
AB  - AIMS: This study evaluated the impact of applying computerized outcome feedback
      (OF) technology in a stepped care psychological service offering low and high
      intensity therapies for depression and anxiety. METHODS: A group of therapists
      were trained to use OF based on routine outcome monitoring using depression (PHQ
      9) and anxiety (GAD-7) measures. Therapists regularly reviewed expected treatment
      response graphs with patients and discussed cases that were "not on track" in
      clinical supervision. Clinical outcomes data were collected for all patients
      treated by this group (N = 594), six months before (controls = 349) and six
      months after the OF training (OF cases = 245). Symptom reductions in PHQ-9 and
      GAD-7 were compared between controls and OF cases using longitudinal multilevel
      modelling. Treatment duration and costs were compared using MANOVA. Qualitative
      interviews with therapists (N = 15) and patients (N = 6) were interpreted using
      thematic analysis. RESULTS: OF technology was generally acceptable and feasible
      to integrate in routine practice. No significant between-group differences were
      found in post-treatment PHQ-9 or GAD-7 measures. However, OF cases had
      significantly lower average duration and cost of treatment compared to controls.
      CONCLUSIONS: After adopting OF into their practice, this group of therapists
      attained similar clinical outcomes but within a shorter space of time and at a
      reduced average cost per treatment episode. We conclude that OF can improve the
      efficiency of stepped care.

PMID- 29024822
TI  - Pubertally Initiated High-Fat Diet Promotes Mammary Tumorigenesis in Obesity
      Prone FVB Mice Similarly to Obesity-Resistant BALB/c Mice.
AB  - Premenopausal breast cancer is associated with increased animal fat consumption
      among normal-weight but not overweight women. Our previous findings in obesity
      resistant BALB/c mice showed that a diet high in saturated animal fat (HFD)
      promotes mammary tumorigenesis in both DMBA carcinogenesis and Trp53-null
      transplant models. Having made these observations in BALB/c mice, which have very
      modest HFD weight gain, we determined the effects of HFD in FVB mice, which gain
      significant weight on HFD. Three-week-old FVB mice fed a low-fat diet or HFD were
      subjected to 7,12-dimethylbenz[a]anthracene-induced carcinogenesis. Like BALB/c
      mice, HFD promoted mammary tumorigenesis. Development of tumors largely occurred
      prior to mice becoming obese, indicating the role of animal-derived HFD rather
      than resulting obesity in tumor promotion. Also similar to BALB/c mice, early
      occurring adenosquamous mammary tumors were abundant among HFD-fed FVB mice.
      Tumors from HFD mice also had increased intra-tumor M2 macrophages. Prior to
      tumor development, HFD accelerated normal mammary gland development and increased
      mammary M2 macrophages, similarly to BALB/c mice. The promotional effects of
      puberty-initiated HFD on carcinogen-induced mammary cancer are thus largely
      weight gain-independent. Like BALB/c mice, HFD promoted adenosquamous tumors,
      suggesting a role for early age HFD in promoting this subtype of triple negative
      mammary cancer. M2 macrophage recruitment was common to both mouse strains. We
      speculate that a similar effect of HFD on immune function may contribute to
      epidemiological findings of increased breast cancer risk in young, premenopausal,
      normal-weight women who consume a diet high in saturated animal fat.

PMID- 29024823
TI  - Genetic Variations of GWAS-Identified Genes and Neuroblastoma Susceptibility: a
      Replication Study in Southern Chinese Children.
AB  - Neuroblastoma is one of the most commonly diagnosed solid cancers for children,
      and genetic factors may play a critical role in neuroblastoma development.
      Previous genome-wide association studies (GWASs) have identified nine genes
      associated with neuroblastoma susceptibility in Caucasians. To determine whether
      genetic variations in these genes are also associated with neuroblastoma
      susceptibility in Southern Chinese children, we genotyped 25 polymorphisms within
      these genes by the TaqMan method in 256 cases and 531 controls. Odds ratios (ORs)
      and 95% confidence intervals (CIs) were used to evaluate the strength of the
      associations. We performed a meta-analysis to further evaluate the associations.
      Furthermore, we calculated the area under the receiver-operating characteristic
      curves (AUC) to assess which gene/genes may better predict neuroblastoma risk. We
      confirmed that CASC15 rs6939340 A>G, rs4712653 T>C, rs9295536 C>A, LIN28B
      rs221634 A>T, and LMO1 rs110419 A>G were associated with significantly altered
      neuroblastoma susceptibility. We also confirmed that rs6939340 A>G (G versus A:
      OR=1.30, 95% CI=1.13-1.50) and rs110419 G>A (A versus G: OR=1.37, 95% CI=1.19
      1.58) were associated with increased neuroblastoma risk for all subjects. We also
      found that the combination of polymorphisms in CASC15, LIN28B, and LMO1 may be
      used to predict neuroblastoma risk (AUC=0.63, 95% CI=0.59-0.67). Overall, we
      verified five GWAS-identified polymorphisms that were associated with
      neuroblastoma susceptibility alteration for Southern Chinese population; however,
      these results need further validation in studies with larger sample sizes.

PMID- 29024824
TI  - Body mass index and fitness in high-functioning children and adolescents with
      cerebral palsy: What happened over a decade?
AB  - BACKGROUND: In recent decades, improving fitness has become an important goal in
      rehabilitation medicine in children and adolescents with cerebral palsy (CP).
      AIMS: To compare body mass index (BMI), performance-related fitness, and
      cardiorespiratory fitness of children with CP measured in 2014 with a comparable
      sample from 2004. METHODS AND PROCEDURES: In total, 25 high-functioning children
      with CP (i.e., GMFCS I-II) measured in 2004 (13 boys; mean age 13.2 (2.6) years)
      were matched to 25 children measured in 2014. Outcomes included body mass and
      BMI, muscle power sprint test (MPST), 10*5m sprint test, and a shuttle run test
      (SRT). Data of 15 participants from 2004 (10 boys; mean age 12.6 (2.5) years)
      were matched and analysed for VO2peak. OUTCOMES AND RESULTS: Body mass and BMI
      were higher (both: p<0.05) in the 2014 cohort compared to the 2004 cohort.
      Further, performance-related fitness was better for the 2014 cohort on the MPST
      (p=0.004), the 10*5m sprint test (p=0.001), and the SRT (p<0.001). However, there
      were no differences for VO2peak. CONCLUSIONS AND IMPLICATIONS: In high
      funcitoning children with CP, there are positive ecological time trends in
      performance-related fitness, but not in VO2peak between 2004 and 2014. The
      substantial higher body mass and BMI is alarming and requires further
      investigation.

PMID- 29024826
TI  - Letter regarding the article "Extending the phenotype of recurrent rearrangements
      of 16p11.2: Deletions in mentally retarded patients without autism and in normal
      individuals ()" and the diagnosis of coexisting Mowat-Wilson syndrome in a
      patient with 16p11.2 deletion.

PMID- 29024825
TI  - A grounded visualization approach to explore sociospatial and temporal
      complexities of older adults' mobility.
AB  - In the past decade, there has been an increasing interest in older adults'
      mobility. Most often, mobility is measured quantitatively as physical movement
      (e.g. physical activity) or travel behavior (e.g. trips, modes, and distances).
      There is a need to integrate both quantitative and qualitative data over time to
      visualize both context and content in a spatial and temporal dimension and
      discover patterns and explanations for their underlying processes. We aim to
      address this gap by demonstrating how a grounded visualization approach can be
      used to explore sociospatial and temporal complexities of older adults' mobility.
      We present two cases of active community (urban) dwelling older adults with low
      incomes (age > 65) who live in Metro Vancouver, Canada, over a period of 4 years.
      Geographical Position Systems (GPS) (QStarz Datalogger BT-Q1000x) data is used to
      capture the destinations participants travel to and the routes they take to get
      there. Survey data provides socio-demographic characteristics and neighborhood
      environments. Interview data capture perceptions, attitudes, and motivations of
      destinations and route choices over time. Integration of the methods identified
      the following themes: spatial perceptions of neighborhood, consistency in travel
      patterns, changes in physical health, familiarity with place and access over
      time. Our grounded visualization approach demonstrates how georeferenced
      qualitative data can be combined with quantitative spatial data to provide a
      deeper understanding of the complexity of older adults' mobility experiences over
      time. Findings illustrate that time is a necessary component of older adults'
      engagement with place; familiarity influences spatial perceptions of local and
      distant 'neighbourhoods'; and older adults prioritize destinations that allow
      them to engage in multiple activities. By integrating methods we are able to gain
      a better understanding of challenges faced by older adults at multiple systems
      levels, and uncover resources and assets available to remediate them.

PMID- 29024827
TI  - Left ventricular non-compaction with Ebstein anomaly attributed to a TPM1
      mutation.
AB  - Left ventricular non-compaction (cardiomyopathy) (LVN(C)) is a rare hereditary
      cardiac condition, resulting from abnormal embryonic myocardial development.
      While it mostly occurs as an isolated condition, association with other
      cardiovascular manifestations such as Ebstein anomaly (EA) has been reported.
      This congenital heart defect is characterized by downward displacement of the
      tricuspid valve and leads to diminished ventricular size and function. In an
      autosomal dominant LVN(C) family consisting of five affected individuals, of
      which two also presented with EA and three with mitral valve insufficiency, we
      pursued the genetic disease cause using whole exome sequencing (WES). WES
      revealed a missense variant (p.Leu113Val) in TPM1 segregating with the LVN(C)
      phenotype. TPM1 encodes alpha-tropomyosin, which is involved in myocardial
      contraction, as well as in stabilization of non-muscle cytoskeletal actin
      filaments. So far, LVN(C)-EA has predominantly been linked to pathogenic variants
      in MYH7. However, one sporadic LVN(C)-EA case with a de novo TPM1 variant has
      recently been described. We here report the first LVN(C)-EA family segregating a
      pathogenic TPM1 variant, further establishing the association between EA
      predisposition and TPM1-related LVN(C). Consequently, we recommend genetic
      testing for both MYH7 and TPM1 in patients or families in which LVN(C)/non
      compaction and EA coincide.

PMID- 29024828
TI  - A classical Ehlers-Danlos syndrome family with incomplete presentation diagnosed
      by molecular testing.
AB  - The 2017 EDS revised nosology indicates that minimal criteria suggestive for
      classical Ehlers-Danlos syndrome (cEDS) are skin hyperextensibility plus atrophic
      scarring together with either generalized joint hypermobility (gJHM) and/or at
      least three minor criteria that include cutaneous features and gJHM
      complications. Confirmatory molecular testing is obligatory to reach a final
      diagnosis. Although the large majority of the patients presents with these
      clinical features, some do not and might remain undiagnosed or misdiagnosed. Here
      we describe a family with 2 affected members, a 23-year-old proposita and her 51
      year-old mother, who presented subtle cutaneous signs, including a variable
      degree of skin hyperextensibility without extensive widened atrophic scars that
      apparently better fitted with the overlapping hypermobile EDS. The proposita also
      presented gastrointestinal symptoms secondary to aberrant mast cells mediators
      release, making the clinical picture even more puzzling. Both patients were
      diagnosed by molecular testing that revealed a COL5A1 splice mutation. This
      report highlights the relevance of molecular analysis in patients presenting
      rather mild signs of EDS, especially in familial cases, and the importance of
      clinical expertise to make such a diagnosis.

PMID- 29024829
TI  - Distal renal tubular acidosis in a Libyan patient: Evidence for digenic
      inheritance.
AB  - AIM OF THE STUDY: Recent advances in understanding the underlying molecular
      mechanism for distal renal tubular acidosis (dRTA), led to an increased attention
      towards the primary and the familial forms of the disease. Mutations in ATP6V1B1
      and ATP6V0A4 are usually responsible for the recessive form of the disease.
      Mutations in gene AE1 encoding the Cl-/HCO3- exchanger, usually present as
      dominant dRTA, but a recessive pattern has been recently described. Our objective
      is to identify the mutational spectrum responsible of dRTA in a consanguineous
      Libyan family. MATERIALS AND METHODS: Both ATP6V0A4 and ATP6V1B1 genes were
      preferentially screened in our patient. Additional whole exome sequencing (WES)
      in the same patient, offered a wider view on potential chromosomal rearrangements
      as well as the mutational spectrum of other genes involved in this disease.
      RESULTS: The patient is a heterozygote for two different mutations, one in each
      of the genes ATP6V0A4 and ATP6V1B1, while no deleterious variation was detected
      in the remaining genes responsible for the recessive form of dRTA. Homozygosity
      mapping and WES confirmed our findings and supported the hypothesis of a digenic
      inheritance model existing as an explanation for dRTA. CONCLUSIONS: To our
      knowledge, this is the first report describing a Libyan patient with dRTA who
      suffered from early-onset sensorineural hearing loss, with a digenic mode of
      inheritance, supported by the identification of two novel mutations. This study
      increases the understanding of how dRTA is genetically transmitted, while offers
      a good outline towards the molecular diagnostics and genetic counseling for dRTA
      in Lybians.

PMID- 29024830
TI  - New ocular finding in Baraitser-Winter syndrome (BWS).
AB  - Baraitser-Winter syndrome was first described as a syndrome of iris coloboma,
      ptosis, hypertelorism, and mental retardation (Baraitser and Winter 1988;
      Baraitser, 2016). The phenotypic spectrum has since broadened to include other
      facial dysmorphic features, deafness, microcephaly, lissencephaly, and CNS
      findings (Baraitser and Winter 1988; Ganesh et al., 2005; Henedy et al., 2010;
      Verloes et al., 2015). The syndrome is due to pathogenic variants on either ACTB
      or ACTG1 genes (Di Donato et al., 2014; Riviere et al., 2012). There is still
      discussion which gene variant produces a more severe phenotype (Di Donato et al.,
      2016; Di Donato et al., 2014; Verloes et al., 2015). We report a 3-year-old girl
      with short stature, mild global developmental delay, minor brain anomalies and
      few dysmorphic features including unusual stroma of the irises and unreported
      corectopia. Exome sequencing reported a de novo likely pathogenic variant on the
      ACTB gene. The present report adds a new ocular finding to the phenotypic
      spectrum.

PMID- 29024831
TI  - Multiple SLC26A2 mutations occurring in a three-generational family.
AB  - Multiple epiphyseal dysplasias (MED) are a group of heterogeneous skeletal
      dysplasias, which share a common phenotype: short stature, skeletal deformities,
      joint pain and early onset osteoarthritis. Mutations in COMP account for
      approximately half of autosomal dominant MED cases whilst SLC26A2 mutations
      account for ~25% of the recessive cases in the Caucasian population. We present
      here an interesting family, which was thought to initially have an autosomal
      dominant skeletal dysplasia. Using a targeted sequencing skeletal dysplasia
      panel, the proband was found to be a compound heterozygote for two mutations in
      SLC26A2, one novel mutation, p.Ser522Phe and the other, the common mutation,
      p.Arg279Trp. In addition to the classical characteristics of MED, she presented
      with an atypical feature, bilateral synostoses between the 2nd and 3rd
      metatarsals. The parents were confirmed to be heterozygous for the two mutations
      but interestingly, the maternal grandfather, who had MED, was found to be
      homozygous for the common SLC26A2 mutation.

PMID- 29024832
TI  - Somatic second hit mutation of RASA1 in vascular endothelial cells in capillary
      malformation-arteriovenous malformation.
AB  - Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal
      dominant vascular disorder that is associated with inherited inactivating
      mutations of the RASA1 gene in the majority of cases. Characteristically,
      patients exhibit one or more focal cutaneous CM that may occur alone or together
      with AVM, arteriovenous fistulas or lymphatic vessel abnormalities. The focal
      nature and varying presentation of lesions has led to the hypothesis that somatic
      "second hit" inactivating mutations of RASA1 are necessary for disease
      development. In this study, we examined CM from four different CM-AVM patients
      for the presence of somatically acquired RASA1 mutations. All four patients were
      shown to possess inactivating heterozygous germline RASA1 mutations. In one of
      the patients, a somatic inactivating RASA1 mutation (c.1534C > T, p.Arg512*) was
      additionally identified in CM lesion tissue. The somatic RASA1 mutation was
      detected within endothelial cells specifically and was in trans with the germline
      RASA1 mutation. Together with the germline RASA1 mutation (c.2125C > T,
      p.Arg709*) in the same patient, the endothelial cell somatic RASA1 mutation
      likely contributed to lesion development. These studies provide the first clear
      evidence of the second hit model of CM-AVM pathogenesis.

PMID- 29024833
TI  - Health of VLBW infants in Germany at five years of age: What do parents describe?
AB  - BACKGROUND: There are only few data on medical problems and utilization of health
      services of former very low birth weight (VLBW) children at preschool age. STUDY
      DESIGN: At five years of age parents of a cohort of VLBW children (N=862)
      received questionnaires, a medical interview and examination. The results were
      compared to the KIGGS cohort (Deutscher-Kinder-und Jugendgesundheitssurvey,
      N=777). RESULTS: Parents of the VLBW and KIGGS cohort reported a very good or
      good health in 95% in their children. When compared to the KIGGS cohort, families
      in the VLBW cohort had a lower social economic status. The VLBW cohort suffered
      more frequently from disabilities (9.6% vs. 1.4%), from chronic bronchitis (45%
      vs. 17%) and from recurrent pain (headaches (20% vs. 7%), ear (16% vs. 6%),
      throat (23% vs. 8%), tooth (10% vs. 3%)). The VLBW cohort received more
      specialized care (ophthalmologist, ENT, orthopaedics, paediatric neurologist).
      CONCLUSION: Families of VLBW children report a good health status in their
      children, but they utilized more specialized care. Higher rates of pain are
      reported in the VLBW cohort. Chronic bronchitis and various upper respiratory
      infections cause an increased morbidity in former VLBW children. Follow up
      programs are needed to develop optimal treatment and prevention strategies for
      these problems.

PMID- 29024834
TI  - Intermittent bilateral anterior sub-costal quadratus lumborum block for effective
      analgesia in lower abdominal surgery.

PMID- 29024835
TI  - Managed access technology to combat contraband cell phones in prison: Findings
      from a process evaluation.
AB  - Cell phones in correctional facilities have emerged as one of the most pervasive
      forms of modern contraband. This issue has been identified as a top priority for
      many correctional administrators in the United States. Managed access, a
      technology that utilizes cellular signals to capture transmissions from
      contraband phones, has received notable attention as a promising tool to combat
      this problem. However, this technology has received little evaluative attention.
      The present study offers a foundational process evaluation and draws upon output
      measures and stakeholder interviews to identify salient operational challenges
      and subsequent lessons learned about implementing and maintaining a managed
      access system. Findings suggest that while managed access captures large volumes
      of contraband cellular transmissions, the technology requires significant
      implementation planning, personnel support, and complex partnerships with
      commercial cellular carriers. Lessons learned provide guidance for practitioners
      to navigate these challenges and for scholars to improve future evaluations of
      managed access.

PMID- 29024836
TI  - Performance of a simple robust empiric timing protocol for CT pulmonary
      angiography.
AB  - OBJECTIVE: We instituted a new, simple CT pulmonary angiography (CTPA) contrast
      material timing protocol using a standard empiric delay to replace our previous
      timing bolus method. This study tests the hypothesis that the empiric protocol
      more consistently produces diagnostic quality images of both the pulmonary
      arteries and the aorta with lower radiation exposure. MATERIALS AND METHODS: We
      performed a retrospective review of consecutive CTPAs for 2months both before and
      after the protocol change. Pulmonary artery and aortic enhancement, patient
      characteristics, radiation exposure and results of CTPA were analyzed. RESULTS:
      There were 182 patients in the timing bolus group and 164 in the empiric timing
      group. Both groups had a female majority (59%) and a similar mean age (58 and
      57years, respectively). Enhancement was significantly higher both for the
      pulmonary artery (median 400HU versus 359HU, P<0.001) and aorta (median 381HU
      versus 218HU, P<0.01) in the empiric timing group versus the timing bolus group,
      respectively. Radiation exposure was lower (5.3mSv versus 6.0mSv, P=0.05) in the
      empiric timing group, despite a higher body-mass-index (31 versus 29kg/m2,
      P<0.01). Pulmonary embolism positivity rate was non-significantly higher in the
      timing bolus vs the empiric timing group (19% and 13%, P=0.1). CONCLUSION: A
      simple empiric timing protocol for CTPA has robust performance compared to a
      timing bolus protocol. Empiric timing preserves the required high diagnostic
      quality for evaluation of the pulmonary arteries with the added benefits of
      aortic enhancement and lower radiation exposure.

PMID- 29024837
TI  - Translating the role of osteogenic-angiogenic coupling in bone formation: Highly
      efficient chitosan-pDNA activated scaffolds can accelerate bone regeneration in
      critical-sized bone defects.
AB  - The clinical translation of bioactive scaffolds for the treatment of large
      segmental bone defects has remained a challenge due to safety and efficacy
      concerns as well as prohibitive costs. The design of an implantable,
      biocompatible and resorbable device, which can fill the defect space, allow for
      cell infiltration, differentiation and neovascularisation, while also
      recapitulating the natural repair process and inducing cells to lay down new bone
      tissue, would alleviate the problems with existing treatments. We have developed
      a gene-activated scaffold platform using a bone-mimicking collagen hydroxyapatite
      scaffold loaded with chitosan nanoparticles carrying genes encoding osteogenic
      (BMP-2) and angiogenic (VEGF) proteins. With a single treatment, protein
      expression by mesenchymal stem cells (MSCs) seeded onto the scaffold is sustained
      for up to 28 days and is functional in inducing MSC osteogenesis. The in vivo
      safety and efficacy of this gene-activated scaffold platform was demonstrated
      resulting in the successful transfection of host cells, abrogating the
      requirement for multiple procedures to isolate cells or ex vivo cell culture.
      Furthermore, the level of bone formation at the exceptionally early time-point of
      28 days was comparable to that achieved following recombinant BMP-2 protein
      delivery after 8 weeks in vivo, without the adverse side effects and at a
      fraction of the cost. This naturally derived cell-free gene-activated scaffold
      thus represents a new 'off-the-shelf' product capable of accelerating bone repair
      in critical-sized bone defects.

PMID- 29024838
TI  - Organ-on-chip models of cancer metastasis for future personalized medicine: From
      chip to the patient.
AB  - Most cancer patients do not die from the primary tumor but from its metastasis.
      Current in vitro and in vivo cancer models are incapable of satisfactorily
      predicting the outcome of various clinical treatments on patients. This is seen
      as a serious limitation and efforts are underway to develop a new generation of
      highly predictive cancer models with advanced capabilities. In this regard, organ
      on-chip models of cancer metastasis emerge as powerful predictors of disease
      progression. They offer physiological-like conditions where the (hypothesized)
      mechanistic determinants of the disease can be assessed with ease. Combined with
      high-throughput characteristics, the employment of organ-on-chip technology would
      allow pharmaceutical companies and clinicians to test new therapeutic compounds
      and therapies. This will permit the screening of a large battery of new drugs in
      a fast and economic manner, to accelerate the diagnosis of the disease in the
      near future, and to test personalized treatments using cells from patients. In
      this review, we describe the latest advances in the field of organ-on-chip models
      of cancer metastasis and their integration with advanced imaging, screening and
      biosensing technologies for future precision medicine applications. We focus on
      their clinical applicability and market opportunities to drive us forward to the
      next generation of tumor models for improved cancer patient theranostics.

PMID- 29024839
TI  - Hepatic artery aneurysm causing gastrointestinal haemorrhage - Case report and
      literature review.
AB  - INTRODUCTION: True hepatic artery aneurysms (HAAs) are rare, and when complicated
      by gastrointestinal haemorrhage, it becomes an even rarer disease entity. The
      mortality is high and imaging may fail to provide the diagnosis. We present a
      case of a true hepatic artery aneurysm complicated by a fistula to the duodenum
      which was first recognised during surgery. PRESENTATION OF CASE: A 77-year-old
      man presented with upper gastrointestinal haemorrhage. Upper endoscopy revealed
      an ulceration in the duodenal bulb, which was refractory to endoscopic treatment.
      Computed tomography and angiography did not reveal the source of haemorrhage and
      as such, the diagnosis was delayed, until laparotomy was performed. Resection of
      the HAA and graft placement resulted in complete haemostasis. DISCUSSION: True
      hepatic aneurysms communicating with the gastrointestinal tract have only been
      presented in case reports and short case series. Arteriosclerosis is a relatively
      common risk factor, but the underlying pathology is unknown. Meanwhile,
      gastrointestinal haemorrhage is a symptom of other, more common diseases in the
      gastrointestinal tract, and these factors, complicate the diagnostic workup.
      CONCLUSION: In the case of treatment refractory duodenal haemorrhage, a visceral
      aneurysm should be considered. Even though angiography is performed, a HAA may
      remain undetected due to bleeding cessation. Improved computed tomography
      modalities could aid in the detection of gastrointestinal haemorrhage from HAAs,
      and ensure timely treatment by endovascular methods or surgery if the diagnosis
      is kept in mind in the initial evaluation.

PMID- 29024840
TI  - A case report of endometriosis presenting as an acute small bowel obstruction.
AB  - INTRODUCTION: Endometriosis is a common and benign condition that causes
      significant morbidity to women of childbearing age. It uncommonly affects the
      gastrointestinal tract and rarely manifests as an acute small bowel obstruction.
      PRESENTATION OF CASE: A 46-year old female presented to the emergency department
      with signs and symptoms consistent with an acute small bowel obstruction. She had
      a paucity of background surgical history, having only had a laparoscopic
      cholecystectomy. Her CT demonstrated small bowel obstruction with a transition
      point in the distal ileum. Given the site of obstruction was remote from previous
      surgery, a high index of suspicion was maintained and early laparoscopy performed
      the same day. Operative findings were consistent with an endometrial stricture of
      the distal ileum and a formal resection was performed. DISCUSSION: Endometriosis
      that affects the gastrointestinal tract often presents with non-specific
      symptoms. This is a rare case of an acute small bowel obstruction as the index
      symptom of endometriosis in a peri-menopausal patient. This is the first case in
      the literature to describe same day laparoscopy and small bowel resection of such
      a case and a prolonged preoperative period and misdiagnoses previously described
      were avoided due to clinical suspicion. CONCLUSION: Endometriosis as a
      differential should be considered with a high index of suspicion in pre
      menopausal women, particularly in patients with negligible previous surgical
      history. There should be a low threshold for early laparoscopy and resection of
      affected bowel in these patients.

PMID- 29024841
TI  - Complicated acute appendicitis presenting as an abscess in the abdominal wall in
      an elderly patient: A case report.
AB  - INTRODUCTION: Appendicitis is a common cause of acute abdomen; however, the
      classic clinical signs are not often present, and it has unusual presentations.
      Thus, its diagnosis can be challenging. PRESENTATION OF CASE: We describe the
      case of an elderly man who presented with right abdominal wall abscess with
      spontaneous drainage in the emergency department. Since we suspected a subjacent
      abdominal pathology, we performed surgery, and intraoperatively, we observed that
      the Appendix tip had invaded the abdominal wall. DISCUSSION: This patient had a
      challenging diagnostic process and surgical visualization of the appendicular tip
      invading the abdominal wall was an important characteristic in proving the cause
      of the abdominal wall abscess. CONCLUSION: The onset of an abdominal wall abscess
      without a known cause needs to be thoroughly investigated, with consideration of
      a subjacent abdominal cause and appendicitis necessitatis.

PMID- 29024842
TI  - Peritoneal carcinomatosis-like implants of extramedullary hematopoiesis. An
      insolite occurrence during splenectomy for myelofibrosis.
AB  - INTRODUCTION: Primary myelofibrosis (MF) is a myeloproliferative neoplasm that
      results in debilitating constitutional symptoms, splenomegaly, and cytopenias. In
      patients with symptomatic splenomegaly, splenectomy remains a viable treatment
      option for MF patients with medically refractory symptomatic splenomegaly that
      precludes the use of ruxolitinib. CASE PRESENTATION: We present the clinical case
      of a patient who was admitted to our Department to perform a splenectomy in MF as
      a therapeutic step prior to an allogeneic stem cell transplantation (ASCT). A
      laparotomic splenectomy and excision of whitish wide-spread peritoneal and
      omental nodulations was performed. There were no operative complications and the
      surgery was completed with minimal blood loss. The histopathological exam
      revealed an extramedullary hematopoiesis in both spleen and peritoneal nodules.
      CONCLUSION: In primary myelofibrosis it must always be kept in mind the possible
      presence of peritoneal implants of extramedullary hematopoiesis and ascites of
      reactive genesis. We report a rare case of peritoneal carcinomatosis-like
      implants of extramedullary hematopoiesis found at splenectomy for MF.

PMID- 29024843
TI  - Multisensory integration and ADHD-like traits: Evidence for an abnormal temporal
      integration window in ADHD.
AB  - Abnormalities in multimodal processing have been found in many developmental
      disorders such as autism and dyslexia. However, surprisingly little empirical
      work has been conducted to test the integrity of multisensory integration in
      Attention Deficit Hyperactivity Disorder (ADHD). The main aim of the present
      study was to examine links between symptoms of ADHD (as measured using a self
      report scale in a healthy adult population) and the temporal aspects of
      multisensory processing. More specifically, a Simultaneity Judgement (SJ) and a
      Temporal Order Judgement (TOJ) task were used in participants with low and high
      levels of ADHD-like traits to measure the temporal integration window and Just
      Noticeable Difference (JND) (respectively) between the timing of an auditory beep
      and a visual pattern presented over a broad range of stimulus onset asynchronies.
      The Point of Subjective Similarity (PSS) was also measured in both cases. In the
      SJ task, participants with high levels of ADHD-like traits considered
      significantly fewer stimuli to be simultaneous than participants with high levels
      of ADHD-like traits, and the former were found to have significantly smaller
      temporal windows of integration (although no difference was found in the PSS in
      the SJ or TOJ tasks, or the JND in the latter). This is the first study to
      identify an abnormal temporal integration window in individuals with ADHD-like
      traits. Perceived temporal misalignment of two or more modalities can lead to
      distractibility (e.g., when the stimulus components from different modalities
      occur separated by too large of a temporal gap). Hence, an abnormality in the
      perception of simultaneity could lead to the increased distractibility seen in
      ADHD.

PMID- 29024845
TI  - Intracerebral stimulation of left and right ventral temporal cortex during object
      naming.
AB  - While object naming is traditionally considered asa left hemisphere function,
      neuroimaging studies have reported activations related to naming in the ventral
      temporal cortex (VTC) bilaterally. Our aim was to use intracerebral electrical
      stimulation to specifically compare left and right VTC in naming. In twenty-three
      epileptic patients tested for visual object naming during stimulation, the
      proportion of naming impairments was significantly higher in the left than in the
      right VTC (31.3% vs 13.6%). The highest proportions of positive naming sites were
      found in the left fusiform gyrus and occipito-temporal sulcus (47.5% and 31.8%).
      For 17 positive left naming sites, an additional semantic picture matching was
      carried out, always successfully performed. Our results showed the enhanced role
      of the left compared to the right VTC in naming and suggest that it may be
      involved in lexical retrieval rather than in semantic processing.

PMID- 29024844
TI  - Structural characterisation of the capsular polysaccharide expressed by
      Burkholderia thailandensis strain E555:: wbiI (pKnock-KmR) and assessment of the
      significance of the 2-O-acetyl group in immune protection.
AB  - Burkholderia pseudomallei and its close relative B. mallei are human pathogens
      that are classified as Tier 1 bio-threat agents. Both organisms have previously
      been shown to constitutively produce a capsular polysaccharide (CPS) that is both
      a virulence determinant and protective antigen. Extraction and purification of
      CPS for use as a potential vaccine candidate requires containment level 3
      laboratories which is expensive and time-consuming. B. thailandensis strain E555
      is closely related to B. pseudomallei and B. mallei, but is non-pathogenic to
      humans and based on immunological cross-reactivity has previously been shown to
      express a B. pseudomallei-like CPS. In this study, capsular polysaccharide
      isolated from an O-antigen deficient strain of B. thailandensis E555 was
      identified by 1H and 13C NMR spectroscopy as -3-)-2-O-acetyl-6-deoxy-beta-d-manno
      heptopyranose-(-1, and identical to that produced by B. pseudomallei. This was
      further substantiated by anti-CPS monoclonal antibody binding. In connection with
      the production of CPS fragments for use in glycoconjugate vaccines, we set out to
      assess the importance or otherwise of the CPS 2-OAc groups in immune protection.
      To this end conjugates of the native and de-O-acetylated CPS with the Hc fragment
      of tetanus toxin (TetHc) were used as vaccines in a mouse model of melioidosis.
      The level of protection provided by deacetylated CPS was significantly lower than
      that from native, acetylated CPS. In addition, sera from mice vaccinated with the
      deacetylated CPS conjugate did not recognise native CPS. This suggests that CPS
      extracted from B. thailandensis can be used as antigen and that the acetyl group
      is essential for protection.

PMID- 29024846
TI  - Attentional control and executive functioning in school-aged children: Linking
      self-regulation and parenting strategies.
AB  - Good parenting strategies can shape children's neurocognitive development, yet
      little is known about the nature of this relation in school-aged children and
      whether this association shifts with age. We aimed to investigate the relation
      between parenting strategies observed during a home visit and children's
      performance-based attentional control and executive functioning (N=98, aged 4
      8years). Linear and curvilinear regression analyses showed that children of
      parents who were more supportive, were less intrusive, and asked more open-ended
      questions displayed better inhibitory control. In addition, children of parents
      who asked relatively more open-ended than closed-ended questions showed better
      performance on inhibition, working memory, and cognitive flexibility tasks.
      Curvilinear relations indicated the presence of an optimal amount of closed-ended
      and elaborative questions by parents-that is, not too few and not too many-which
      is linked to increased performance on attentional and inhibitory control in
      children. Higher parental intrusiveness and more frequent elaborative questioning
      were associated with decreased inhibitory control in younger children, whereas no
      such negative associations were present in older children. These results suggest
      that susceptibility to certain parenting strategies may shift with age. Our
      findings underscore the importance of adaptive parenting strategies to both the
      age and needs of school-aged children, which may positively affect their self
      regulation skills.

PMID- 29024847
TI  - How children remember the Strange Situation: The role of attachment.
AB  - This study tested predictions from Bowlby's attachment theory about children's
      memory and suggestibility. Young children (3-5years old, N=88; 76% Caucasians)
      and their parents took part in the Strange Situation Procedure, a moderately
      distressing event and "gold standard" for assessing children's attachment
      quality. The children were then interviewed about what occurred during the event.
      Children's age and attachment security scores positively predicted correct
      information in free recall and accuracy in answering specific questions. For
      children with higher (vs. lower) attachment security scores, greater distress
      observed during the Strange Situation Procedure predicted increased resistance to
      misleading suggestions. In addition, for children who displayed relatively low
      distress during the Strange Situation Procedure, significant age differences in
      memory and suggestibility emerged as expected. However, for children who
      displayed greater distress during the Strange Situation Procedure, younger and
      older children's memory performances were equivalent. Findings suggest that
      attachment theory provides an important framework for understanding facets of
      memory development with respect to attachment-related information and that
      distress may alter assumed age patterns in memory development.

PMID- 29024848
TI  - Incorporation of surface plasmon resonance with novel valinomycin doped chitosan
      graphene oxide thin film for sensing potassium ion.
AB  - In this study, the combination of novel valinomycin doped chitosan-graphene oxide
      (C-GO-V) thin film and surface plasmon resonance (SPR) system for potassium ion
      (K+) detection has been developed. The novel C-GO-V thin film was deposited on
      the gold surface using spin coating technique. The system was used to monitor SPR
      signal for K+ in solution with and without C-GO-V thin film. The K+ can be
      detected by measuring the SPR signal when C-GO-V thin film is exposed to K+ in
      solution. The sensor produces a linear response for K+ ion up to 100ppm with
      sensitivity and detection limit of 0.00948 degrees ppm-1 and 0.001ppm,
      respectively. These results indicate that the C-GO-V film is high potential as a
      sensor element for K+ that has been proved by the SPR measurement.

PMID- 29024849
TI  - Hydrogen sulfide alleviates the cold stress through MPK4 in Arabidopsis thaliana.
AB  - Hydrogen sulfide (H2S) is a gaseous signaling molecule that mediates
      physiological processes in animals and plants. In this study, we investigated the
      relationship of H2S and mitogen activated protein kinase (MAPK) under cold stress
      in Arabidopsis. H2S up-regulated MAPK expression levels and was involved in the
      cold stress-related upregulation of MAPK genes expression. We then chose MPK4
      whose expression level was influenced the most by H2S as a target and found that
      H2S's ability to alleviate cold stress required MPK4. Both H2S and MPK4 regulated
      the expression levels of the cold response genes inducer of CBF expression 1
      (ICE1), C-repeat-binding factors (CBF3), cold responsive 15A (COR15A) and cold
      responsive 15B (COR15B). H2S inhibited the opening of stomata under cold stress,
      which required the participation of MPK4. In conclusion, MPK4 is a downstream
      component of H2S-related cold-stress resistance, and H2S and MPK4 both regulated
      the cold response genes and stomatal movement to response the cold stress.

PMID- 29024850
TI  - Combined effects of fungal inoculants and the cytokinin-like growth regulator
      thidiazuron on growth, phytohormone contents and endophytic root fungi in
      Miscanthus * giganteus.
AB  - Aim of this study was to investigate main effects and interactions between
      symbiotic fungi and the cytokinin-like growth regulator thidiazuron (TDZ) in
      Miscanthus * giganteus. The arbuscular mycorrhiza fungus Rhizophagus intraradices
      (AMF) and the endophyte Piriformospora indica (PI) were chosen as model
      symbionts. The fungal inoculants and TDZ had no significant effect on plant
      growth but modulated phytohormone levels in the leaves. TDZ induced accumulation
      of salicylic acid in controls, but not in plants inoculated with fungi. Leaf
      concentrations of abscisic acid (ABA) derivatives, auxin (indole-3-acetic acid)
      precursors and catabolites and numerous cytokinins were increased by R.
      intraradices but lowered by P. indica. TDZ raised concentrations of ABA
      compounds, the non-indole auxin phenylacetic acid, jasmonate and some cytokinins,
      but decreased cis-zeatin and N6-(Delta2-isopentenyl)adenine levels. Inoculation
      with AMF reduced abundance of endogenous clampless endophytes. TDZ application
      strongly reduced formation of arbuscular mycorrhiza and increased occurrence of
      clamped mycelia (i.e. basidiomycetous endophytes). Our study provides a thorough
      outline of the phytohormone homeostasis under the combined influence of
      beneficial inoculants and a growth regulator, highlighting the necessity to study
      their interaction in the whole plant-microbial context.

PMID- 29024851
TI  - Infectivity of Sf-rhabdovirus variants in insect and mammalian cell lines.
AB  - Sf-rhabdovirus was only recently identified as an adventitious agent of
      Spodoptera frugiperda (Sf) cell lines used as hosts for baculovirus vectors. As
      such, we still know little about its genetic variation, infectivity, and the
      potential impact of variation on the Sf-rhabdovirus-host interaction. Here, we
      characterized Sf-rhabdoviruses from two widely used Sf cell lines to confirm and
      extend information on Sf-rhabdovirus variation. We then used our novel Sf
      rhabdovirus-negative (Sf-RVN) Sf cell line to assess the infectivity of variants
      with and without a 320bp X/L deletion and found both established productive
      persistent infections in Sf-RVN cells. We also assessed their infectivity using
      heterologous insect and mammalian cell lines and found neither established
      productive persistent infections in these cells. These results are the first to
      directly demonstrate Sf-rhabdoviruses are infectious for Sf cells, irrespective
      of the X/L deletion. They also confirm and extend previous results indicating Sf
      rhabdoviruses have a narrow host range.

PMID- 29024852
TI  - The cation-selective exhaustive injection and sweeping capillary electrophoresis
      method for the analysis of chlorpheniramine enantiomers in rat plasma.
AB  - Chlorpheniramine is a potent antihistaminic administered as a racemic mixture,
      while its clinical activity is mainly associated with the S-enantiomer. In this
      study, a sensitive and rapid on-line preconcentration capillary electrophoresis
      (CE) method, cation-selective exhaustive injection (CSEI) and sweeping method was
      established and validated for the analysis of two chlorpheniramine enantiomers.
      Parameters influencing separation and enhancement efficiency were investigated,
      including cyclodextrin (CD) types and concentration, background electrolyte pH,
      type and content of organic modifier, injection time of water plug, injection
      time and voltage of sample. A zone of 30mM Tris buffer at pH 3.5 without chiral
      selector was injected into the capillary followed by a 3s water plug, allowing
      for the analytes to be electrokinetically injected at a voltage of 10kV for 80s.
      A 30mM Tris buffer at pH 3.5 consisting of 20mM sulfated-beta-cyclodextrin (S
      beta-CD) and 5% methanol was found to be highly efficient for the separation of
      the two enantiomers. The present method manifested that high sensitivity
      (0.025MUg/mL for the thethe lower limit of quantification), satisfactory accuracy
      (89.2%-95.0%) and precision (relative standard deviation within 8.4%) were
      achieved as well as favourable stability. The extraction recoveries of two
      enantiomers were both above 72.5%. Finally, the developed method was successfully
      applied to pharmacokinetic study of the two enantiomers in rat plasma after oral
      administration of racemic chlorpheniramine.

PMID- 29024854
TI  - The effect of associative strength on semantic priming in schizophrenia.
AB  - The present research was designed to investigate the pattern of semantic priming
      in schizophrenia as a function of strength of association (or semantic distance
      between concepts in the semantic network). Thirty schizophrenia patients, without
      formal thought disorder, and twenty-nine healthy controls participated in a
      lexical decision task in which prime-target associative strength (strong, weak
      and not related) and stimulus-onset asynchrony (SOA: 250ms and 750ms) were
      manipulated. Patients and controls showed the same associative strength effect on
      RTs. In the short SOA condition priming effects were obtained for both strong and
      weak prime-target associative conditions. However in the long SOA priming was
      only significant for strongly associated pairs. This pattern of priming effects
      was similar in both groups, with higher priming on the short SOA and strong
      association conditions. Altogether results suggest that automatic semantic
      spreading activation is unimpaired in schizophrenia patients without formal
      thought disorder. These results are in line with the general evidence of impaired
      implicit priming observed only in patients with formal thought disorder. At the
      same time patients use context as controls to facilitate word processing.
      Finally, these findings evidence that, prime-target associative strength could
      moderate results in studies of semantic memory deficits in schizophrenia.

PMID- 29024853
TI  - Overexpression of constitutively active MAP3K7 in ameloblasts causes enamel
      defects of mouse teeth.
AB  - OBJECTIVE: Compelling evidence suggests that mitogen-activated protein kinases
      (Mapks) play an important role in amelogenesis. However, the role of transforming
      growth factor (TGF)-beta-activating kinase 1 (Tak1, Map3k7), which is a known
      upstream kinase of Mapks, during amelogenesis remains to be determined. The aim
      of this study was to investigate the possible involvement of Map3k7 in
      amelogenesis. DESIGN: We generated transgenic mice that produced constitutively
      active human MAP3K7 (caMAP3K7) under the control of amelogenin (Amelx) gene
      promoter. Radiography and micro-computed tomography (MUCT) analysis was used to
      detect the radio-opacity and density of the teeth. The enamel microstructure was
      observed with a scanning electron microscope. Histological analysis was used to
      observe the adhesion between ameloblasts and residual organic matrix of the
      enamel. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to
      analyze the expression of enamel matrix protein. RESULTS: The enamel of
      mandibular molars in caMAP3K7-overexpressing mice displayed pigmentation and a
      highly irregular structure compared with the wild type littermates. Teeth of
      transgenic animals underwent rapid attrition due to the brittleness of the enamel
      layer. The microstructure of enamel, normally a highly ordered arrangement of
      hydroxyapatite crystals, was completely disorganized. The gross histological
      appearances of ameloblasts and supporting cellular structures, as well as the
      expression of the enamel protein amelotin (Amtn) were altered by the
      overexpression of caMAP3K7. CONCLUSIONS: Our data demonstrated that protein
      expression, processing and secretion occurred abnormally in transgenic mice
      overexpressing caMAP3K7. The overexpression of caMAP3K7 had a profound effect on
      enamel structure by disrupting the orderly growth of enamel prisms.

PMID- 29024855
TI  - The relationship between schizotypal facets and conspiracist beliefs via
      cognitive processes.
AB  - This study sought to replicate previous work showing relationships between
      components of schizotypy and conspiracist beliefs, and extend it by examining the
      mediating role of cognitive processes. An international online sample of 411
      women and men (mean age = 35.41 years) completed measures of the schizotypal
      facets of Odd Beliefs or Magical Thinking and Ideas of Reference, conspiracist
      beliefs, and cognitive processes related to need for cognition, analytic
      thinking, and cognitive insight. Path analysis confirmed the associations between
      both schizotypal facets and conspiracist beliefs in the present sample.
      Confirmatory evidence was found for the association between analytic thinking and
      conspiracist beliefs, and results also suggested an association between cognitive
      insight and conspiracist beliefs. Cognitive insight also mediated the link
      between Odd Beliefs or Magical Thinking and Ideas of Reference with conspiracist
      beliefs. However, analytic thinking provided a mediating link to conspiracy
      ideation for Odd Beliefs or Magical Thinking and not Ideas of Reference. Finally,
      there was an association between Odd Beliefs or Magical Thinking and need for
      cognition, but this path did not extend to conspiracist beliefs. These results
      suggest possible mediating roles for analytic thinking and self-certainty between
      schizotypy and conspiracist beliefs.

PMID- 29024856
TI  - Social cognition and African American men: The roles of perceived discrimination
      and experimenter race on task performance.
AB  - The Social Cognition Psychometric Evaluation (SCOPE) study consists of a battery
      of eight tasks selected to measure social-cognitive deficits in individuals with
      schizophrenia. The battery is currently in a multisite validation process. While
      the SCOPE study collects basic demographic data, more nuanced race-related
      factors might artificially inflate cross-cultural differences in social
      cognition. As an initial step, we investigated whether race, independent of
      mental illness status, affects performance on the SCOPE battery. Thus, we
      examined the effects of perceived discrimination and experimenter race on the
      performance of 51 non-clinical African American men on the SCOPE battery. Results
      revealed that these factors impacted social cognitive task performance.
      Specifically, participants performed better on a skills-based task factor in the
      presence of Black experimenters, and frequency of perceived racism predicted
      increased perception of hostility in negative interpersonal situations with
      accidental causes. Thus, race-related factors are important to identify and
      explore in the measurement of social cognition in African Americans.

PMID- 29024857
TI  - Controlled trial evaluation of exposure duration to negative air ions for the
      treatment of seasonal affective disorder.
AB  - This study evaluated the effectiveness of 30 or 60min of daily exposure to high
      density or to zero-density (placebo condition) negative air ions over 18 days on
      the symptoms of seasonal affective disorder (SAD) in 40 participants under
      controlled laboratory conditions. Exposure to high-density negative air ions was
      superior to zero-density negative air ions in alleviating depression and the
      atypical symptoms of SAD. Also, more subjects in the high-density negative air
      ions groups met two different clinical response criteria than did those in the
      zero-density groups. Within the high density treatment group, both the short and
      long daily exposure reduced SAD symptoms. Exposure to negative air ions produced
      no negative side effects, and no ozone was produced by the ion generators. In
      both the high-density negative air ions and zero-density negative air ions
      groups, a significant placebo effect was found for most clinical measures.
      Finally, for the high-density negative air ion groups, subjects with a
      morningness chronotype responded better to treatment with high-density negative
      air ions than did those with an eveningness chronotype.

PMID- 29024858
TI  - Motion modes of two self-propelled camphor boats on the surface of a surfactant
      containing solution.
AB  - HYPOTHESIS: The existence of a surface tension difference and a surface flow
      around self-propelled objects, such as camphor boats, has been confirmed by many
      studies. However, the interactions in the collective motion of several camphor
      boats have not been explicitly discussed. Here, a model system of two camphor
      boats was investigated for the first time from the viewpoint of surface tension
      and surface flow. EXPERIMENTS: The behavior of one fixed boat and one movable
      boat on a sodium dodecylsulfate aqueous solution in an oval track has been
      studied as a model system of two-body interactions. The surface tension around
      the movable boat was measured using the non-invasive, double-beam quasi-elastic
      laser scattering method. The Marangoni surface flow was quantitatively estimated
      using a mock boat in order to evaluate the net repulsive interaction between the
      two boats. FINDINGS: We succeeded in controlling the motion of the two camphor
      boats by varying the boat characteristics and the surfactant concentration. The
      balance/unbalance between the surface tension distribution and the surface flow
      around the boats was found to drive two different behavior modes: stationary and
      oscillatory. These results allow us to gain further insight into the dynamics of
      the interactions in the collective behavior of autonomous inanimate objects.

PMID- 29024859
TI  - Effect of calcination temperature of a copper ferrite synthesized by a sol-gel
      method on its structural characteristics and performance as Fenton catalyst to
      remove gallic acid from water.
AB  - A copper ferrite synthesized by a sol-gel combustion method was calcined at
      different temperatures up to 800 degrees C, determining changes in its structural
      characteristics and magnetic measurements and studying its catalytic performance
      in gallic acid removal by Fenton reaction. The main objective was to study the
      effect of the calcination temperature of copper ferrite on its crystalline phase
      formation and transformation, activity and metal ion leaching. The cubic-to
      tetragonal transformation of the spinel occurred via its reaction with the CuO
      phase, displacing Fe3+ ions in B (octahedral) sites out of the spinel structure
      by the following reaction: 2Fe3+B+3CuO->Fe2O3+3Cu2+B. The catalysts showed
      superparamagnetic or substantial superparamagnetic behaviour. At higher
      calcination temperatures, catalyst activity was lower, and Cu ion leaching was
      markedly decreased. There was no Fe ion leaching with any catalyst. The as
      prepared catalyst showed better catalytic performance than a commercial copper
      ferrite. Leached Cu ions acted as homogeneous catalysts, and their contribution
      to the overall removal mechanism was examined. Cu2O present in the as-prepared
      catalysts made only a small contribution to their activity. Finally, the
      reutilization of various catalysts was studied by performing different catalytic
      cycles.

PMID- 29024860
TI  - Facile synthesis N-doped hollow carbon spheres from spherical solid silica.
AB  - Nitrogen-doped core/shell carbon nanospheres (NHCS are prepared and their
      capability as an anode material in lithium-ion batteries is investigated. The
      synthesis methodology is based on a fast template route. The resulting molecular
      nanostructures are characterized by X-ray diffraction, transmission electron
      microscopy, thermal analysis, and nitrogen adsorption/desorption measurement as
      well as by cyclic voltammetry and galvanostatic cycling. The core/shell structure
      provides a rapid lithium transport pathway and boasts a highly reversible
      capacity. For undoped HCS the BET specific surface area is 623m2/g which
      increases up to 1000m2/g upon N-doping. While there is no significant effect of N
      doping on the electrochemical performance at small scan rates, the doped NHCS
      shows better specific capacities than the pristine HCS at elevated rates. For
      instance, the discharge capacities in the 40th cycle, obtained at 1000mA/g,
      amount to 170mAh/g and 138mAh/g for NHCS and HCS, respectively.

PMID- 29024861
TI  - Tunable photoluminescence of MoS2 quantum dots passivated by different functional
      groups.
AB  - Recently, transitional metal dichalcogenides quantum dots have attracted much
      interest as a potential candidate for the application of fluorescent materials.
      However, little work has been done on tuning their band gap by varying functional
      groups. Here, we report a band-gap tunability of 1eV in the MoS2 quantum dots
      (QDs) modified by different functional groups. In our results, it has also been
      confirmed that a tunable band gap in the MoS2 QDs can be achieved by
      monotonically varying the concentration of a functional group. A mechanism has
      also been proposed to explain the enhanced photoluminescence behaviors in the
      functionalized MoS2 QDs. Our work provides a general guideline to develop other
      semiconducting QDs to be future impressive fluorescent materials.

PMID- 29024862
TI  - 4-phenylbutyrate and valproate treatment attenuates the progression of
      atherosclerosis and stabilizes existing plaques.
AB  - BACKGROUND AND AIMS: Recent evidence suggests that endoplasmic reticulum (ER)
      stress signaling through glycogen synthase kinase (GSK)-3alpha/beta is involved
      in the activation of pro-atherosclerotic processes. In this study, we examined
      the effects of small molecules that interfere with ER stress-GSK3alpha/beta
      signaling on the progression and regression of atherosclerosis in a mouse model.
      METHODS: To examine atherosclerotic progression, low-density lipoprotein receptor
      deficient (Ldlr-/-) mice were placed on a high-fat diet (HFD) and treated with
      the chemical chaperone, 4-phenylbutyrate (4PBA, 3.8  g/L drinking water), or the
      GSK3alpha/beta inhibitor, valproate (VPA, 625 mg VPA/kg diet), for 10 weeks. To
      examine potential effects on atherosclerotic regression, 4 week old Ldlr-/- mice
      were placed on a HFD for 16 weeks. Subsets of mice were harvested at this time or
      switched to a chow (low fat) diet, or a chow diet with 4PBA or VPA treatment for
      4 weeks. RESULTS: In the progression model, the 4PBA- and VPA-treated mice had
      significantly reduced lesion and necrotic core size. Treatments had no effect on
      metabolic parameters, including plasma and hepatic lipid levels, or plaque
      composition. In the regression model, mice with 4PBA or VPA treatment showed no
      alterations in lesion size, but the lesions had significantly smaller necrotic
      cores, increased vascular smooth muscle cell content, and increased collagen
      content. These features are consistent with more stable plaques. CONCLUSIONS: The
      pharmacological attenuation of ER stress or inhibition of GSK3alpha/beta impedes
      the development of atherosclerosis in Ldlr-/- mice and appears to promote the
      stabilization of existing lesions.

PMID- 29024863
TI  - Environmental tobacco smoke and peripheral arterial disease: A review.
AB  - BACKGROUND AND AIMS: Despite worldwide reductions in active smoking, non-smokers
      continue to be exposed to environmental tobacco smoke, especially at home or
      workplace. There is a well-recognised association between active smoking and
      peripheral arterial disease, however, a relationship to environmental tobacco
      smoke exposure is less substantiated. The aims of this paper are to review the
      literature regarding the association between environmental tobacco smoke and
      peripheral arterial disease and identify the public health implications of the
      findings. METHODS: Selected electronic databases (Medline, EMBASE, CINAHL,
      PsychINFO and Scopus) were searched for studies published up to August 2017. Key
      words and inclusion/exclusion criteria applied. A manual search of reference
      lists of studies selected for review was also performed. RESULTS: Of the initial
      150 studies identified, 12 met inclusion criteria for review. Three studies
      showed a positive association between environmental tobacco smoke exposure and
      definitive diagnosis of peripheral arterial disease, 6 studies demonstrated a
      positive association with features of vascular injury, and 3 studies found no
      significant positive or negative association. CONCLUSIONS: An association between
      exposure to environmental tobacco smoke and development of peripheral arterial
      disease or clinically significant arterial injury in non-smokers is supported by
      moderate quality evidence in the literature. Larger, longitudinal observational
      studies addressing current limitations, including sources of bias, inconsistency
      and imprecision, are needed to provide more robust and consistent evidence.
      Regardless, evidence of potential detrimental impacts supports ongoing
      restrictions on freedom to smoke in public areas, including the workplace, and
      has implications for those exposed in the home environment.

PMID- 29024864
TI  - Association between serum uric acid level and renal arteriolar hyalinization in
      individuals without chronic kidney disease.
AB  - BACKGROUND AND AIMS: Recent studies have reported an association between serum
      uric acid (SUA) and renal arteriolar changes in patients with chronic kidney
      disease (CKD). However, the association in individuals without CKD remains
      unclear. In this study, we investigated the relationship between SUA and renal
      arteriolar lesions in individuals without CKD from our living kidney donor
      cohort. METHODS: Between January 2006 and May 2016, 393 living kidney donors
      underwent "time-zero" biopsy at Kyushu University Hospital. Patients were divided
      into sex-specific quartiles of SUA before donation: Q1, Q2, Q3, and Q4 (male:
      <5.2,5.2-5.8,5.9-6.4, and >=6.5 mg/dL, female: <3.8,3.8-4.3,4.4-5.0, and >=5.1
      mg/dL). Renal arteriolar hyalinization and wall thickening were assessed using a
      semiquantitative grading system. Predictive performance was compared between
      models with and without SUA by calculating the net reclassification improvement
      (NRI). RESULTS: In total, 158 (40.2%) patients had arteriolar hyalinization, and
      148 (37.6%) had wall thickening. High SUA was significantly associated with
      arteriolar hyalinization in multivariable logistic analysis (odds ratio [OR] per
      1-mg/dL increase in SUA, 1.24; 95% confidence interval [CI], 1.00-1.53; p =
      0.048. OR for Q4 vs. Q2, 2.22; 95% CI, 1.17-4.21; p = 0.01). We found no
      association between SUA and wall thickening. When SUA was incorporated into a
      predictive model with conventional atherosclerotic factors, the NRI was 0.21 (p =
      0.04). CONCLUSIONS: High SUA was an independent risk factor for arteriolar
      hyalinization in individuals without CKD. SUA provided additional predictive
      value beyond conventional atherosclerotic factors in predicting arteriolar
      hyalinization.

PMID- 29024867
TI  - Management of generalized seizures after face allotransplantation: The first
      clinical report.

PMID- 29024865
TI  - Impaired kidney function is associated with intraplaque hemorrhage in patients
      undergoing carotid endarterectomy.
AB  - BACKGROUND AND AIMS: Previously, we showed that patients undergoing carotid
      endarterectomy have an increased risk for major atherosclerotic events in the
      presence of moderate or poor kidney function. Acceleration of vascular
      inflammatory responses is considered to be causally involved in progression of
      atherogenesis and poor outcome in chronic kidney disease patients. The
      association between kidney function and plaque composition has not been
      thoroughly investigated yet. The aim of this study was to investigate the
      association between kidney function and atherosclerotic plaque composition in
      patients undergoing carotid endarterectomy. METHODS: Atherosclerotic plaques,
      harvested from 1796 patients who underwent carotid endarterectomy, were
      immunohistochemically stained for macrophages, smooth muscle cells,
      calcifications, collagen, microvessels, lipid core size and intraplaque
      hemorrhage. Cytokines were measured in plaque and plasma and associated with
      kidney function. Quantitative proteomics were performed on 40 carotid plaques and
      associated with kidney function. RESULTS: Decreased kidney function was
      associated with increased odds ratio of intraplaque hemorrhage, OR 1.15 (95% CI;
      1.02-1.29 (p = 0.024)) and increased odds ratio of fibrous-atheromatous plaques
      (plaques with lipid core presenting more than 10% of total plaque surface) OR
      1.21 (95% CI; 1.07-1.38 (p = 0.003)) per decrease of 20 points in eGFR.
      Proteomics revealed that decreased kidney function was associated with
      upregulation of the classical pathway of the complement system and the intrinsic
      pathway of the coagulation system. CONCLUSIONS: Decreased kidney function was
      associated with plaque hemorrhage but not with inflammatory plaque
      characteristics. Our data suggests that other pathways than the inflammation
      pathway are involved in plaque vulnerability and poor outcome in patients with
      decreased kidney function.

PMID- 29024866
TI  - Diclofenac but not celecoxib improves endothelial function in rheumatoid
      arthritis: A study in adjuvant-induced arthritis.
AB  - BACKGROUND AND AIMS: We aimed at investigating the effect of celecoxib (COX-2
      selective inhibitor) and diclofenac (non-selective COX inhibitor) on endothelial
      function, and at identifying the underlying mechanisms in adjuvant-induced
      arthritis (AIA). METHODS: At the first signs of AIA, diclofenac (5 mg/kg twice a
      day, i.p), celecoxib (3 mg/kg/day, i.p) or saline (Vehicle) was administered for
      3 weeks. Endothelial function was studied in aortic rings relaxed with
      acetylcholine (Ach) with or without inhibitors of NOS, arginase, EDHF and
      superoxide anions (O2- degrees ) production. Aortic expression of eNOS, Ser1177
      phospho-eNOS, COX-2, arginase-2, p22phox and p47phox was evaluated by Western
      blotting analysis. Arthritis scores, blood pressure, glycaemia and serum ADMA
      levels were measured. RESULTS: Diclofenac and celecoxib significantly reduced
      arthritis score to the same extent (p<0.05). As compared to vehicle-treated AIA,
      celecoxib did not change whereas diclofenac improved endothelial function
      (p<0.05) through increased EDHF production, decreased arginase activity and
      expression, decreased superoxide anions production and expression of p22phox and
      p47phox. Diclofenac but not celecoxib significantly enhanced blood pressure and
      serum ADMA levels. Glycaemia was unchanged by both treatments. CONCLUSIONS: Our
      study reveals that the effect of NSAIDs on endothelial function cannot be
      extrapolated from their impact on arthritis severity and suggest that changes in
      blood pressure and plasma ADMA levels may not be useful to predict CV risk of
      NSAIDs in RA.

PMID- 29024868
TI  - Introduction of non-invasive prenatal testing as a first-tier aneuploidy
      screening test: A survey among Dutch midwives about their role as counsellors.
AB  - In 2014, non-invasive prenatal testing (NIPT) for trisomies 21, 18 and 13 was
      added to the Dutch prenatal screening program as part of the TRIDENT study. Most
      (85%) pregnant Dutch women are counselled for prenatal aneuploidy screening by
      primary care midwives. This will remain when NIPT is implemented as a first-tier
      screening test. We therefore investigated midwife counsellors': 1) Knowledge
      about NIPT; 2) Attitudes towards NIPT as first-tier screening test; and 3)
      Experiences with informing clients about NIPT. Between April-June 2015, an online
      questionnaire to assess knowledge about NIPT, attitudes towards NIPT, and
      experiences with NIPT was completed by 436 Dutch primary care midwives. We found
      that 59% midwives answered >=7 of 8 knowledge questions correctly. Continuing
      professional education attendance and more positive attitudes towards prenatal
      screening for Down syndrome were positively associated with the total knowledge
      score (beta = 0.261; p = 0.007 and beta = 0.204; p = 0.015, respectively). The
      majority (67%) were in favor of replacing First trimester Combined Test with
      NIPT, although 41% preferred to maintain a nuchal translucency measurement
      alongside NIPT. We conclude that midwives demonstrated solid knowledge about NIPT
      that may still be improved in some areas. Dutch midwives overwhelmingly support
      the integration of NIPT as a first-tier screening test.

PMID- 29024869
TI  - Mapping midwifery and obstetric units in England.
AB  - OBJECTIVE: to describe the configuration of midwifery units, both alongside&free
      standing, and obstetric units in England. DESIGN: national survey amongst Heads
      of Midwifery in English Maternity Services SETTING: National Health Service (NHS)
      in England PARTICIPANTS: English Maternity Services Measurements descriptive
      statistics of Alongside Midwifery Units and Free-standing Midwifery Units and
      Obstetric Units and their annual births/year in English Maternity Services
      FINDINGS: alongside midwifery units have nearly doubled since 2010 (n = 53-97);
      free-standing midwifery units have increased slightly (n = 58-61). There has been
      a significant reduction in maternity services without either an alongside or free
      standing midwifery unit (75-32). The percentage of all births in midwifery units
      has trebled, now representing 14% of all births in England. This masks
      significant differences in percentage of all births in midwifery units between
      different maternity services with a spread of 4% to 31%. KEY CONCLUSIONS: In some
      areas of England, women have no access to a local midwifery unit, despite the
      National Institute for Health&Clinical Excellence (NICE) recommending them as an
      important place of birth option for low risk women. The numbers of midwifery
      units have increased significantly in England since 2010 but this growth is
      almost exclusively in alongside midwifery units. The percentage of women giving
      birth in midwifery units varies significantly between maternity services
      suggesting that many midwifery units are underutilised. IMPLICATIONS FOR
      PRACTICE: Both the availability and utilisation of midwifery units in England
      could be improved.

PMID- 29024870
TI  - Comparable effectiveness and immunomodulatory actions of oxaliplatin and
      cisplatin in electrochemotherapy of murine melanoma.
AB  - Interest in platinum-based chemotherapeutics such as oxaliplatin (OXA) and
      cisplatin (CDDP) has been reinvigorated by their newly described impacts on tumor
      specific immune responses. In addition to CDDP, OXA is frequently used to treat
      cancers. Based on the characteristics of OXA, which are similar to those of CDDP,
      and the presumably more pronounced immunomodulatory effect of OXA, OXA is a
      candidate for electrochemotherapy (ECT). We compared the effectiveness of
      intratumoral ECT with OXA to that of ECT with CDDP in murine B16F10 melanoma to
      determine the equieffective dose. Special attention was given to the elicitation
      of immunogenic cell death and local immune response. Based on the in vitro and in
      vivo results pertaining to effectiveness and drug uptake in cells and tumors, ECT
      with OXA is as effective as ECT with CDDP when the OXA dose is increased 1.6
      fold. Exposure of melanoma cells to ECT induces immunogenic cell death when
      either OXA or CDDP is used, which correlates with a comparable increase in
      lymphocyte infiltration into tumors after ECT with either OXA or CDDP. Based on
      these results, OXA is a valid platinum-based drug for use with ECT, and the
      effectiveness of ECT with OXA is comparable to that of the well-established ECT
      with CDDP. Furthermore, both drugs display equal and specific immune responses
      following ECT.

PMID- 29024872
TI  - A (salicylaldiminato)Pt(II) complex with dimethylpropylene linkage: Synthesis,
      structural characterization and antineoplastic activity.
AB  - A novel (salicylaldiminato)Pt(II) complex with two different molecular
      structures, one solventless ((salicylaldiminato)Pt(II)) 1 and another one
      solvated ((salicylaldiminato)Pt(II). C2H5OH), 1.C2H5OH, has been obtained by the
      reaction of a salen ligand with [PtCl2(DMSO)2] in ethanol at room temperature.
      The asymmetric unit of solventless 1 contains 9 such complex molecules whereas
      1.C2H5OH contains 2 complex molecules and one ethanol molecule. To get insights
      into the structure and bonding, DFT and TDFT calculation have been carried out.
      The electronic transition band at 408.0nm (calc. 424.3nm) is assigned to HOMO
      >LUMO (96%) excitation. The calculated NMR chemical shifts are interrelated with
      the experimental results, and a very slight effect of solvent was noticed on NMR
      chemical shifts. A MTT assay and the real-time cell monitoring xCELLigence system
      revealed that the 1 has significant potential to suppress cell viability and cell
      proliferation in human HT-29 and SW620 colorectal cancer cell lines.

PMID- 29024871
TI  - Brain energetics during the sleep-wake cycle.
AB  - Brain activity during wakefulness is associated with high metabolic rates that
      are believed to support information processing and memory encoding. In spite of
      loss of consciousness, sleep still carries a substantial energy cost.
      Experimental evidence supports a cerebral metabolic shift taking place during
      sleep that suppresses aerobic glycolysis, a hallmark of environment-oriented
      waking behavior and synaptic plasticity. Recent studies reveal that glial
      astrocytes respond to the reduction of wake-promoting neuromodulators by
      regulating volume, composition and glymphatic drainage of interstitial fluid.
      These events are accompanied by changes in neuronal discharge patterns, astrocyte
      neuron interactions, synaptic transactions and underlying metabolic features.
      Internally-generated neuronal activity and network homeostasis are proposed to
      account for the high sleep-related energy demand.

PMID- 29024873
TI  - Photodynamic therapy for Schistosoma mansoni: Promising outcomes.
AB  - The purpose of this study was to assess, for the very first time, the effects of
      photodynamic therapy (PDT) on Schistosoma mansoni in vitro by measuring reactive
      oxygen species (ROS) generation throughout the treatment, as well as the behavior
      of the parasites (mating, motility and contraction/shortening), and damage to
      their tegument and excretory systems. The parasites were divided into 4 groups:
      control, photosensitizer, laser and PDT. Light irradiation was delivered with an
      InGaAlP low-level laser device operating at 660nm, with 40mW and 100J/cm2. For
      PDT, different toluidine blue dye (TBO) concentrations and times of exposure were
      utilized. Interestingly, TBO-mediated PDT was able to kill S. mansoni (P<0.001)
      due to the significant amount of ROS released that inflicted damages in the
      tegument and excretory system, as well as contraction and cessation of motility.
      In addition, males of S. mansoni were shown to be more sensitive to PDT if
      compared to their corresponding females when the optimal TBO concentration of
      31.2MUL was considered (P=0.0126). PDT presents two major advantages: not
      inducing microbial resistance and also lacking adverse effects. Therefore, PDT
      may become a promising therapeutic alternative for schistosomiasis in the near
      future, especially for cases of allergy and resistance to praziquantel.

PMID- 29024874
TI  - Electrical impedance myography changes after incomplete cervical spinal cord
      injury: An examination of hand muscles.
AB  - OBJECTIVE: This study was to apply the newly developed electrical impedance
      myography (EIM) technique to examine hand muscles in patients with an incomplete
      cervical spinal cord injury (SCI). METHODS: EIM was performed on the thenar,
      hypothenar, and first dorsal interosseous (FDI) muscles of SCI (n=16) and age
      matched healthy control (n=18) subjects. By sending low intensity and high
      frequency current through the skin and measuring the consequent voltage, EIM
      estimates the major impedance parameters, which include resistance (R), reactance
      (X) and phase angle (theta). RESULTS: The SCI group had lower reactance and phase
      angle (p<0.0001) as compared to the control group in all three muscles, and lower
      resistance in the thenar muscle (p<0.05). The SCI group also demonstrated a
      smaller anisotropy in resistance (p<0.0001) and larger anisotropy in phase angle
      (p<0.05) compared to those from healthy controls. CONCLUSION: The reduced
      reactance and phase angle of paralyzed muscles could be due tochanges of membrane
      integrity and fat infiltration, whereas the change in the anisotropy may reflect
      the rearrangement of muscle fiber geometry. SIGNIFICANCE: The EIM provides a
      quick and convenient tool for examination of muscle alterations after SCI.

PMID- 29024876
TI  - Design of a dielectric resonator receive array at 7 Tesla using detunable ceramic
      resonators.
AB  - Ceramic-based dielectric resonators can be used for high frequency magnetic
      resonance imaging and microscopy. When used as elements in a transmit array, the
      intrinsically low inter-element coupling allows flexibility in designing
      different geometric arrangements for different regions-of-interest. However,
      without being able to detune such resonators, they cannot be used as elements in
      a receive-only array. Here, we propose and implement a method, based on mode
      disruption, for detuning ceramic-based dielectric resonators to enable them to be
      used as receive-only elements.

PMID- 29024875
TI  - Social networking online to recover from opioid use disorder: A study of
      community interactions.
AB  - BACKGROUND: Social media has increasingly become a venue for health discourse and
      support, particularly for vulnerable individuals. This study examines user
      generated content of an online Reddit community targeting individuals recovering
      from opiate addiction. METHODS: 100 Reddit posts and their comments were
      collected from the online community on August 19, 2016. Posts were qualitatively
      coded for opioid use disorder (OUD) criteria as outlined by the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-5), as well as other common themes.
      Comments were coded for expression of distinct therapeutic factors (i.e.,
      instillation of hope, universality, imparting information, and altruism). All
      posts and comments were coded for addiction phase of the author (i.e., using,
      withdrawing, recovering). RESULTS: 73 unique usernames authored the 100 posts.
      Among the 73 usernames, 33% (24/73) described enough symptoms in their posts to
      meet DSM-V criteria for OUD (16/73 or 22% mild severity, 7/73 or 10% moderate
      severity, and 1/73 or 1% high severity. Among the 100 posts, advice was requested
      in 43% (43/100) of the posts and support was sought in 24% (24/100) of the posts.
      There were 511 comments made on the 100 posts, nearly all of which contained at
      least one distinct therapeutic factor (486/511, 95%) with altruism being the most
      common (341/511, 67%). CONCLUSIONS: This research provides validity to the
      supportive content generated on an online recovery-oriented community, while also
      revealing discussions of self-reported struggles with OUD among group members.
      Future research should explore the feasibility of incorporating social media
      based peer support into traditional addiction treatments.

PMID- 29024877
TI  - Zernike phase contrast in high-energy x-ray transmission microscopy based on
      refractive optics.
AB  - The current work represents the first implementation of Zernike phase contrast
      for compound refractive lens based x-ray microscopy, and also the first
      successful Zernike phase contrast experiment at photon energies above 12 keV.
      Phase contrast was achieved by fitting a compound refractive lens with a circular
      phase plate. The resolution is demonstrated to be sub-micron, and can be improved
      using already existing technology. The possibility of combining the technique
      with polychromatic radiation is considered, and a preliminary test experiment was
      performed with positive results.

PMID- 29024878
TI  - Impact of outlier status on critical care patient outcomes: Does boarding medical
      intensive care unit patients make a difference?
AB  - PURPOSE: To evaluate the impact of outlier status, or the practice of boarding
      ICU patients in distant critical care units, on clinical and utilization
      outcomes. MATERIALS AND METHODS: Retrospective observational study of all
      consecutive admissions to the MICU service between April 1, 2014-January 3, 2016,
      at an urban university hospital. RESULTS: Of 1931 patients, 117 were outliers
      (6.1%) for the entire duration of their ICU stay. In adjusted analyses, there was
      no association between outlier status and hospital (OR 1.21, 95% CI 0.72-2.05,
      p=0.47) or ICU mortality (OR 1.20, 95% CI 0.64-2.25, p=0.57). Outliers had
      shorter hospital and ICU lengths of stay (LOS) in addition to fewer ventilator
      days. Crossover patients who had variable outlier exposure also had no increase
      in hospital (OR 1.61; 95% CI 0.80-3.23; p=0.18) or ICU mortality (OR 1.05; 95% CI
      0.43-2.54; p=0.92) after risk-adjustment. CONCLUSIONS: Boarding of MICU patients
      in distant units during times of bed nonavailability does not negatively
      influence patient mortality or LOS. Increased hospital and ventilator utilization
      observed among non-outliers in the home unit may be attributable, at least in
      part, to differences in patient characteristics. Prospective investigation into
      the practice of ICU boarding will provide further confirmation of its safety.

PMID- 29024879
TI  - Single intervention for a reduction in portable chest radiography (pCXR) in
      cardiovascular and surgical/trauma ICUs and associated outcomes.
AB  - PURPOSE: Studies suggest that "on-demand" radiography is equivalent to daily
      routine with regard to adverse events. In these studies, provider behavior is
      controlled. Pragmatic implementation has not been studied. MATERIALS AND METHODS:
      This was a quasi-experimental, pre-post intervention study. Medical directors of
      two intervention ICUs requested pCXRs be ordered on an on-demand basis at one
      time point, without controlling or monitoring behavior or providing follow-up.
      RESULTS: A total of 11,994 patient days over 18months were included. Combined
      characteristics: Age: 56.7, 66% male, 96% survival, APACHE II 14 (IQR: 11-19),
      mechanical ventilation (MV) (occurrences)/patient admission: mean 0.7 (SD: 0.6;
      range: 0-5), duration (hours) of MV: 21.7 (IQR: 9.8-81.4) and ICU LOS (days): 2.8
      (IQR: 1.8-5.6). Average pCXR rate/patient/day before was 0.93 (95% CI: 0.89
      0.96), and 0.73 (95% CI: 0.69-0.77) after. Controlling for severity, daily pCXR
      rate decreased by 21.7% (p<0.001), then increased by about 3%/month (p=0.044).
      There was no change in APACHE II, mortality, and occurrences or duration of MV,
      unplanned re-intubations, ICU LOS. CONCLUSIONS: In critically ill adults, pCXR
      reduction can be achieved in cardiothoracic and trauma/surgical patients with a
      pragmatic intervention, without adversely affecting patient care, outside a
      controlled study.

PMID- 29024880
TI  - Experience with and amount of postpartum maternity care: Comparing women who
      rated the care they received from the maternity care assistant as 'good' or 'less
      than good care'.
AB  - OBJECTIVE: The postpartum period is an important time in the lives of new
      mothers, their children and their families. The aim of postpartum care is 'to
      detect health problems of mother and/or baby at an early stage, to encourage
      breastfeeding and to give families a good start' (Wiegers, 2006). The Netherlands
      maternity care system aims to enable every new family to receive postpartum care
      in their home by a maternity care assistant (MCA). In order to better understand
      this approach, in this study we focus on women who experienced the postpartum
      care by the MCA as 'less than good' care. Our research questions are; among
      postpartum women in the Netherlands, what is the uptake of MCA care and what
      factors are significantly associated with women's rating of care provided by the
      MCA. Design and setting This study uses data from the 'DELIVER study', a dynamic
      cohort study, which was set up to investigate the organization, accessibility and
      quality of primary midwifery care in the Netherlands. Participants In the DELIVER
      population 95.6% of the women indicated that they had received postpartum
      maternity care by an MCA in their home. We included the responses of 3170 women.
      MEASUREMENTS AND FINDINGS: To assess the factors that were significantly
      associated with reporting 'less than good (postpartum) care' by the MCA, a full
      cases backward logistic regression model was built using the multilevel approach
      in Generalized Linear Mixed Models. FINDINGS: The mean rating of the postpartum
      care by the MCA was 8.8 (on a scale from 1-10), and 444 women (14%) rated the
      postpartum maternity care by the MCA as 'less than good care'. In the full cases
      multivariable analysis model, odds of reporting 'less than good care' by the MCA
      were significantly higher for women who were younger (women 25-35 years had an OR
      1.32, CI 0.96-1.81 and women 35 years), multiparous (OR 1.27, CI 1.01-1.60) and
      had a higher level of education (women with a middle level had an OR 1.84,CI 1.22
      2.79, and women with a high level of education had an OR 2.11, CI 1.40-3.18
      compared to women with a low level of education). Odds of reporting 'less than
      good care' were higher for women who, received the minimum amount of hours (OR
      1.86, CI 1.45-2.38), in their opinion received not enough or too many hours
      maternity care assistance (OR 1.47, CI 1.01-2.15 and OR 5.15, CI 3.25-8.15,
      respectively), received care from two or more different MCAs (2 MCAs OR 1.61 CI
      1.24-2.08, >=3 MCAs OR 3.01, CI 1.98-4.56 compared to 1 MCA) and rated the care
      of the midwife as less than good care (OR 4.03, CI 3.10-5.25) . The odds of
      reporting 'less than good care' were lower for women whose reason for choosing
      maternity care assistance was to get information and advice (OR 0.52, CI 0.41
      0.65). KEY CONCLUSIONS: We conclude that (the postpartum) MCA care is well
      utilised, and highly rated by most women. IMPLICATIONS FOR PRACTICE: The approach
      to care in the Netherlands addresses the needs as outlined by NICE and WHO.
      Although no data exists around the impact of use on maternal infant outcomes,
      this approach might be useful in other jurisdictions. MCA care might be improved
      if the hours of MCA care were tailored, and care by multiple MCAs minimised.

PMID- 29024881
TI  - A pilot randomised controlled trial exploring the effects of antenatal
      reflexology on labour outcomes.
AB  - OBJECTIVE: to investigate the effects of antenatal reflexology on labour
      outcomes. DESIGN: secondary analysis of a pilot three-armed randomised controlled
      trial conducted between July 2012 and September 2013. SETTING: a large UK inner
      city hospital maternity department. PARTICIPANTS: ninety primiparous women with a
      singleton pregnancy experiencing low back and / or pelvic girdle pain.
      INTERVENTIONS: six weekly 30-minute reflexology treatments compared to sham
      (footbath) treatments or usual antenatal care only. MEASUREMENTS: labour outcome
      data including labour onset, duration of the second stage of labour, epidural and
      Entonox usage, and mode of delivery. Participant feedback was collected prior to
      each treatment. FINDINGS: labour outcomes were collected for 61 women (95.3%) who
      completed the study. The second stage of labour duration data, available for 42
      women (62.5%) who had vaginal births, showed a mean reduction of 44minutes in the
      reflexology group (73.56minutes; SD= 53.78) compared to the usual care
      (117.92minutes; SD=56.15) (p<0.05) and footbath groups (117.4minutes; SD=68.54)
      (p=0.08). No adverse effects were reported. KEY CONCLUSIONS: in this trial
      antenatal reflexology reduced labour duration for primiparous women who had
      experienced low back and/ or pelvic girdle pain during their pregnancy, compared
      with usual care and footbaths. IMPLICATIONS FOR PRACTICE: reflexology is suitable
      for use during pregnancy, is safe and enjoyable and may reduce labour duration.
      Midwives may wish to recommend reflexology to promote normal childbirth and
      facilitate women centred care. TRIAL REGISTRATION: this trial was listed with the
      International Standard Randomised Controlled Trial Number Register
      (ISRCTN26607527).

PMID- 29024882
TI  - Quantitative mapping of elements in basil leaves (Ocimum basilicum) based on
      cesium concentration and growth period using laser ablation ICP-MS.
AB  - Quantitative elemental mapping of metallic pollutants in sweet basil was studied
      by laser ablation (LA)-ICP-MS. For this, the sweet basil was cultivated in
      Hoagland nutrient solution spiked with 100 and 1000 ng mL-1 of Cs for 10-60 days.
      Then, the Cs distribution in collected leaves was determined by LA-ICP-MS using
      lab-synthesized standard pellets based on NIST 1573a tomato leaves. For
      comparison, S, Ca, and K were also simultaneously determined in this measurement
      with a13C+ signal from the leaves as an internal standard. The obtained
      calibration curves showed linear coefficient of determination (R2) of 0.991 for K
      and 0.999 for Cs. The concentration of Cs measured in the basil leaves increased
      with growth period and pollutant concentration, and accumulation followed the
      order of leaf margin, petiole, midrib, and veins. Although no visible symptom was
      detected, significant suppression of the growth rate was observed due to the
      presence of high-concentration Cs. The experimental model demonstrated herein
      showed potential for studying the influence of radioactive pollutants on plants
      and other organisms in the food chain.

PMID- 29024883
TI  - Emerging organic pollutants in the vadose zone of a soil aquifer treatment
      system: Pore water extraction using positive displacement.
AB  - Trace organic compounds in effluents, water streams and aquifers are amply
      reported. However, the mobile pool of Emerging Organic Contaminants (EOCs) in the
      deep parts of the vadose zone is hard to estimate, due to difficulties in
      extraction of sufficient quantity of pore water. Here, we present a new
      methodology for depth profiling of EOCs in pore water by Positive Displacement
      Extraction (PDE): Pore water extraction from unsaturated soil samples is carried
      out by withdrawal of soil cores by direct-push drilling and infiltrating the core
      by organics free water. We show that EOC concentrations in the water eluted in
      the plateau region of the inverse breakthrough curve is equal to their pore water
      concentrations. The method was previously validated for DOC extraction, and here
      the scope of the methodology is extended to pore water extraction for organic
      pollutants analysis. Method characteristics and validation were carried out with
      atrazine, simazine, carbamazepine, venlafaxine, O-desmethylvenlafaxine and
      caffeine in the concentration range of several ng to several MUg/liter.
      Validation was carried out by laboratory experiments on three different soils
      (sandy, sandy-clayey and clayey). Field studies in the vadose zone of a SAT
      system provided 27 m deep EOC profiles with less than 1.5 m spatial resolution.
      During the percolation treatment, carbamazepine remained persistent, while the
      other studied EOCs were attenuated to the extent of 50-99%.The highest
      degradation rate of all studied EOCs was in the aerobic zone. EOC levels based on
      PDE and extraction by centrifugation were compared, showing a positive bias for
      centrifugation.

PMID- 29024884
TI  - Adsorption-desorption and hysteresis phenomenon of tebuconazole in Colombian
      agricultural soils: Experimental assays and mathematical approaches.
AB  - The adsorption-desorption, hysteresis phenomenon, and leachability of
      tebuconazole were studied for Inceptisol and Histosol soils at the surface (0-10
      cm) and in the subsurface (40-50 cm) of an agricultural region from Colombia by
      the batch-equilibrium method and mathematical approaches. The experimental Kfa
      and Kd (L kg-1) values (7.9-289.2) decreased with depth for the two Inceptisols
      and increased with depth for the Histosol due to the organic carbon content, aryl
      and carbonyl carbon types. Single-point and desorption isotherms depended on
      adsorption reversibility and suggested that tebuconazole showed hysteresis; which
      can be adequately evaluated with the single-point desorption isotherm and the
      linear model using the hysteresis index HI. The most suitable mathematical
      approach to estimate the adsorption isotherms of tebuconazole at the surface and
      in the subsurface was that considering the combination of the n-octanol-water
      partition coefficient, pesticide solubility, and the mass-balance concept.
      Tebuconazole had similar moderate mobility potential as compared with the values
      of other studies conducted in temperate amended and unamended soils, but the risk
      of the fungicide to pollute groundwater sources increased when the pesticide
      reached subsurface soil layers, particularly in the Inceptisols.

PMID- 29024885
TI  - Degradation of Reactive Black 5 by electrochemical oxidation.
AB  - Degradation of commercial grade Reactive Black 5 (RB5) azo dye by chemical and
      electrochemical treatment was examined using a dimensionally stable anode and
      stainless steel cathodes as electrode materials, with NaCl as supporting
      electrolyte. The electrochemical treatment was compared to the chemical treatment
      with hypochlorite generated by electrolysis. The compounds present in the
      commercial grade RB5 azo dye and the products of its electrochemical degradation
      were separated using ion-pairing high performance liquid chromatography on
      reversed phase. The separated species were detected by diode array detector and
      electrospray ionization mass spectrometry. A suitable ion-pairing reversed phase
      HPLC-MS method with electrospray ionization for the separation and identification
      of the components was developed. The accurate mass of the parent and fragment
      ions were used in the determination of the empirical formulas of the components
      using the first-order mass spectra. Structural formulas of degradation products
      were proposed using these information and principles of organic chemistry and
      electrochemistry.

PMID- 29024886
TI  - A case study to identify priority cytostatic contaminants in hospital effluents.
AB  - This study analyses the presence of 17 cytostatic agents from seven different
      groups, based on their different mechanisms of action, in the effluent from a
      medium-sized hospital located in eastern Spain. Analysis of the compounds found
      in the effluents studied involved solidphase extraction (SPE) coupled on-line to
      a high performance liquid chromatograph tandem mass spectrometer (HPLC-MS/MS).
      The environmental risk of the compounds studied was then assessed by calculating
      the hazard quotient (HQ), combining the measured environmental concentrations
      (MECs) with dose-response data based on the predicted no effect concentrations
      (PNECs). In addition, the environmental hazard associated was evaluated in
      accordance with their intrinsic characteristics by calculating the PBT
      (Persistence Bioaccumulation Toxicity) index. The results of this study showed
      the presence of seven of the 17 compounds analysed in a range of between 25 and
      4761 ng/L. The highest concentrations corresponded to ifosfamide (58-4761 ng/L),
      methotrexate (394-4756 ng/L) and cyclophosphamide (46-3000 ng/L). Assessment of
      the environmental hazard showed that the three hormonal agents (tamoxifen and its
      metabolites endoxifen and hydroxytamoxifen) exhibited a maximum PBT value of 9
      due to their inherent harm to the environment resulting from their
      characteristics of persistence, bioaccumulation and toxicity. A combined
      evaluation of the risk and environmental hazard showed that three of the 17
      compounds studied, namely, ifosfamide, imatinib and irinotecan, all of which
      exhibited HQ values higher than 10 and PBT indices of 6, indicative of a
      particularly high potential to harm the environment, deserve special attention.

PMID- 29024887
TI  - Simultaneous removal of NO and SO2 using vacuum ultraviolet light
      (VUV)/heat/peroxymonosulfate (PMS).
AB  - Simultaneous removal process of SO2 and NO from flue gas using vacuum ultraviolet
      light (VUV)/heat/peroxymonosulfate (PMS) in a VUV spraying reactor was proposed.
      The key influencing factors, active species, reaction products and mechanism of
      SO2 and NO simultaneous removal were investigated. The results show that vacuum
      ultraviolet light (185 nm) achieves the highest NO removal efficiency and yield
      of and under the same test conditions. NO removal is enhanced at higher PMS
      concentration, light intensity and oxygen concentration, and is inhibited at
      higher NO concentration, SO2 concentration and solution pH. Solution temperature
      has a double impact on NO removal. CO2 concentration has no obvious effect on NO
      removal. and produced from VUV-activation of PMS play a leading role in NO
      removal. O3 and .O produced from VUV-activation of O2 also play an important role
      in NO removal. SO2 achieves complete removal under all experimental conditions
      due to its very high solubility in water and good reactivity. The highest
      simultaneous removal efficiency of SO2 and NO reaches 100% and 91.3%,
      respectively.

PMID- 29024888
TI  - Synthetic plant glycans.
AB  - For more than a century the primary carbon source for the production of fuels,
      chemicals and many materials has been fossil resources. Recently, plant
      polysaccharides from non-food biomass have emerged as a promising renewable
      alternative that may displace a significant fraction of petroleum-derived
      products. As a food source, plant polysaccharides can provide beneficial effects
      on the human immune system in the form of dietary fiber. Despite the strong
      impact of plant glycans on society and human health, their chemical synthesis
      remains largely unexplored compared to the synthesis of mammalian and bacterial
      glycans. Synthetic glycans such as described in this review provide an important
      toolbox for studying the role of carbohydrates in plant biology and their
      interaction with human health.

PMID- 29024889
TI  - Unitary and dual models of phenomenal consciousness.
AB  - There is almost unanimous consensus among the theorists of consciousness that the
      phenomenal character of a mental state cannot exist without consciousness. We
      argue for a reappraisal of this consensus. We distinguish two models of
      phenomenal consciousness: unitary and dual. Unitary model takes the production of
      a phenomenal quality and it's becoming conscious to be one and the same thing.
      The dual model, which we advocate in this paper, distinguishes the process in
      which the phenomenal quality is formed from the process that makes this quality
      conscious. We put forward a conceptual, methodological, neuropsychological and
      neural argument for the dual model. These arguments are independent but provide
      mutual support to each other. Together, they strongly support the dual model of
      phenomenal consciousness and the concomitant idea of unconscious mental
      qualities. The dual view is thus, we submit, a hypothesis worthy of further
      probing and development.

PMID- 29024890
TI  - A systematic review of economic evaluation in pancreatic ductal adenocarcinoma.
AB  - OBJECTIVES: The economic evaluation (EE) of healthcare interventions has become a
      necessity. However, high quality needs to be ensured in order to achieve
      validated results and help making informed decisions. Thus, the objective of the
      present study was to systematically identify and review published pancreatic
      ductal adenocarcinoma-related EEs and to assess their quality. METHODS:
      Systematic literature research was conducted in PubMed and Cochrane to identify
      published EEs between 2000 and 2015. The quality of each selected EE was assessed
      by two independent reviewers, using the Drummond's checklist. RESULTS: Our
      systematic review was based on 32 EEs and showed a wide variety of methodological
      approaches, including different perspectives, time horizon, and cost
      effectiveness analyses. Nearly two-thirds of EEs are full EEs (n = 21), and about
      one-third of EEs had a Drummond score >=7, synonymous with 'high quality'. Close
      to 50% of full EEs had a Drummond score >=7, whereas all of partial EEs had a
      Drummond score <7 (n = 11). CONCLUSIONS: Over the past 15 years, a lot of
      interest has been evinced over the EE of pancreatic ductal adenocarcinoma (PDAC)
      and its direct impact on therapeutic advances in PDAC. To provide a framework for
      health care decision-making, to facilitate transferability and to lend
      credibility to health EEs, their quality must be improved. For the last 4 years,
      a tendency towards a quality improvement of these studies has been observed,
      probably coupled with a context of rational decision-making in health care, a
      better and wider spread of recommendations and thus, medical practitioners' full
      endorsement.

PMID- 29024891
TI  - Mentalizing and interpersonal problems in borderline personality disorder: The
      mediating role of identity diffusion.
AB  - Individuals with borderline personality disorder (BPD) are characterized by
      problems in interpersonal functioning and their long-term social integration
      often remains problematic. Extant theories have linked identity diffusion to many
      of the interpersonal problems characteristic of BPD patients. Recent theoretical
      accounts have suggested that identity diffusion results from problems with
      mentalizing or reflective functioning, that is, the capacity to understand
      oneself and others in terms of intentional mental states. In this study we tested
      these assumptions, i.e., whether identity diffusion plays a mediating role in the
      relationship between mentalizing difficulties and interpersonal problems, in a
      sample of 167 BPD patients. Highly significant correlations were found between
      mentalizing impairments, identity diffusion and interpersonal problems. Mediation
      analyses showed that identity diffusion fully mediated the relationship between
      mentalizing difficulties and interpersonal problems. This study provides
      preliminary evidence that impairments in mentalizing are related to identity
      diffusion, which in turn is related to interpersonal problems in BPD. Further
      longitudinal research is needed to further substantiate these conclusions.

PMID- 29024892
TI  - Life review therapy enhances mental time travel in patients with schizophrenia.
AB  - Mental Time Travel (MTT) is the ability of individuals to project themselves to
      the past or to the future. Studies have shown that schizophrenia (SZ) patients
      are impaired in MTT. The present study aimed to examine whether MTT in patients
      with SZ can be improved through Life Review Therapy. Fifty patients with SZ were
      randomly assigned to the training (SZ-training) or control (SZ-control) group.
      Whereas the SZ-training group received four-week Life Review Therapy in addition
      to conventional treatment, the SZ-control group only received conventional
      treatment. MTT, emotional status, life satisfaction and cognitive functions were
      assessed before and after the training. We also recruited 25 matched healthy
      controls to complete all the assessments at baseline. After training, the SZ
      training group showed higher specificity and more field perspective than the SZ
      control group. No significant difference was found between the SZ-training group
      post-training assessment and the healthy controls. The SZ-training group also
      showed significant improvements in emotional expression, semantic memory and
      verbal fluency, but the SZ-control group did not show such improvements. These
      results indicated that Life Review Therapy is effective in improving MTT of SZ
      patients.

PMID- 29024893
TI  - Plasma ratio of clozapine to N-desmethylclozapine can predict cognitive
      performance in treatment-resistant psychotic patients.
AB  - Cognitive symptoms play a central role in schizophrenia and are strongly
      associated with social functioning. Treatment with clozapine presents
      controversial results regarding its effects on cognition. The opposite effects of
      clozapine and n-desmethylclozapine (NDMC) on cholinergic system have been
      suggested to underlie these inconclusive findings. The aim of this study is to
      determine whether clozapine/NDMC ratio can predict cognitive performance in
      patients with treatment-resistant psychosis. Nineteen clinically stable patients
      with schizophrenia or schizoaffective disorder treated with clozapine monotherapy
      completed demographic and clinical interviews. For the purpose of the study,
      patients were assessed with a neuropsychological battery and on the same day a
      blood sampling was obtained from each patient to measure plasma levels of
      clozapine and NDMC. Our results showed that clozapine/NDMC ratio, but not
      clozapine or NDMC plasma levels separately, was a predictive factor of cognitive
      performance, specifically of executive functioning. Our results showed that lower
      clozapine/NDMC ratios are associated with better executive functioning in
      clinically stable patients. These findings could be interpreted by the different
      pharmacodynamic properties on cholinergic, dopaminergic and serotonergic systems
      of NDMC compared to clozapine.

PMID- 29024894
TI  - High strength yttria-reinforced HA scaffolds fabricated via honeycomb ceramic
      extrusion.
AB  - The present study investigated the effects of hydroxyapatite (HA) reinforced with
      yttria on porous scaffolds fabricated via honeycomb ceramic extrusion. Yttria was
      selected as it has been demonstrated to toughen other ceramics. Moreover, yttria
      has been surmised to suppress dehydroxylation in HA, a characteristic that
      prefigures decomposition thereof during sintering into mechanically weaker
      phases. However, the compressive strength of yttria-reinforced hydroxyapatite (Y
      HA) porous scaffolds has hitherto not been reported. Y-HA was synthesised by
      calcining a commercially available HA with 10wt% yttria at 1000 degrees C. Y-HA
      was then fabricated into porous scaffolds using an in-house honeycomb extruder,
      and subsequently sintered at 1200 and 1250 degrees C. The results were compared
      to the uncalcined as-received commercial powder (AR-HA) and calcined pure HA
      powder at 1000 degrees C (C-HA). It was discovered that calcination alone caused
      marked improvements to the stoichiometry, thermal stability, porosity and
      compressive strength of scaffolds. The improvements were ascribed to the calcined
      powders with less susceptibility to both agglomeration and enhanced
      densification. Still, differences were observed between C-HA and Y-HA at 1250
      degrees C. The compressive strength increased from 105.9 to 127.3MPa, a larger
      microporosity was descried and the HA matrix in Y-HA was more stoichiometric. The
      latter was confirmed by XRD and EDS analyses. Therefore, it was concluded that
      the reinforcing of hydroxyapatite with yttria improved the compressive strength
      and suppressed dehydroxylation of porous HA scaffolds. In addition, the
      compressive strength achieved demonstrated great potential for load-bearing
      application.

PMID- 29024895
TI  - Over length quantification of the multiaxial mechanical properties of the
      ascending, descending and abdominal aorta using Digital Image Correlation.
AB  - In this paper, we hypothesize that the biaxial mechanical properties of the aorta
      may be dependent on arterial location. To demonstrate any possible position
      related difference, our study analyzed and compared the biaxial mechanical
      properties of the ascending thoracic aorta, descending thoracic aorta and
      infrarenal abdominal aorta stemming from the same porcine subjects, and reported
      values of constitutive parameters for well-known strain energy functions, showing
      how these mechanical properties are affected by location along the aorta. When
      comparing ascending thoracic aorta, descending thoracic aorta and infrarenal
      abdominal aorta, abdominal tissues were found to be stiffer and highly
      anisotropic. We found that the aorta changed from a more isotropic to a more
      anisotropic tissue and became progressively less compliant and stiffer with the
      distance to the heart. We observed substantial differences in the anisotropy
      parameter between aortic samples where abdominal samples were more anisotropic
      and nonlinear than the thoracic samples. The phenomenological model was not able
      to capture the passive biaxial properties of each specific porcine aorta over a
      wide range of biaxial deformations, showing the best prediction root mean square
      error epsilon=0.2621 for ascending thoracic samples and, especially, the worst
      for the infrarenal abdominal samples epsilon=0.3780. The micro-structured model
      with Bingham orientation density function was able to better predict biaxial
      deformations (epsilon=0.1372 for ascending thoracic aorta samples). The root mean
      square error of the micro-structural model and the micro-structured model with
      von Mises orientation density function were similar for all positions.

PMID- 29024897
TI  - A framework for engaging stakeholders on the management of alien species.
AB  - Alien species can have major ecological and socioeconomic impacts in their novel
      ranges and so effective management actions are needed. However, management can be
      contentious and create conflicts, especially when stakeholders who benefit from
      alien species are different from those who incur costs. Such conflicts of
      interests mean that management strategies can often not be implemented. There is,
      therefore, increasing interest in engaging stakeholders affected by alien species
      or by their management. Through a facilitated workshop and consultation process
      including academics and managers working on a variety of organisms and in
      different areas (urban and rural) and ecosystems (terrestrial and aquatic), we
      developed a framework for engaging stakeholders in the management of alien
      species. The proposed framework for stakeholder engagement consists of 12 steps:
      (1) identify stakeholders; (2) select key stakeholders for engagement; (3)
      explore key stakeholders' perceptions and develop initial aims for management;
      (4) engage key stakeholders in the development of a draft management strategy;
      (5) re-explore key stakeholders' perceptions and revise the aims of the strategy;
      (6) co-design general aims, management objectives and time frames with key
      stakeholders; (7) co-design a management strategy; (8) facilitate stakeholders'
      ownership of the strategy and adapt as required; and (9) implement the strategy
      and monitor management actions to evaluate the need for additional or future
      actions. In case additional management is needed after these actions take place,
      some extra steps should be taken: (10) identify any new stakeholders, benefits,
      and costs; (11) monitor engagement; and (12) revise management strategy. Overall,
      we believe that our framework provides an effective approach to minimize the
      impact of conflicts created by alien species management.

PMID- 29024896
TI  - Identification of a soluble guanylate cyclase in RBCs: preserved activity in
      patients with coronary artery disease.
AB  - Endothelial dysfunction is associated with decreased NO bioavailability and
      impaired activation of the NO receptor soluble guanylate cyclase (sGC) in the
      vasculature and in platelets. Red blood cells (RBCs) are known to produce NO
      under hypoxic and normoxic conditions; however evidence of expression and/or
      activity of sGC and downstream signaling pathway including phopshodiesterase
      (PDE)-5 and protein kinase G (PKG) in RBCs is still controversial. In the present
      study, we aimed to investigate whether RBCs carry a functional sGC signaling
      pathway and to address whether this pathway is compromised in coronary artery
      disease (CAD). Using two independent chromatographic procedures, we here
      demonstrate that human and murine RBCs carry a catalytically active alpha1beta1
      sGC (isoform 1), which converts 32P-GTP into 32P-cGMP, as well as PDE5 and PKG.
      Specific sGC stimulation by NO+BAY 41-2272 increases intracellular cGMP-levels up
      to 1000-fold with concomitant activation of the canonical PKG/VASP-signaling
      pathway. This response to NO is blunted in alpha1-sGC knockout (KO) RBCs, but
      fully preserved in alpha2-sGC KO. In patients with stable CAD and endothelial
      dysfunction red cell eNOS expression is decreased as compared to aged-matched
      controls; by contrast, red cell sGC expression/activity and responsiveness to NO
      are fully preserved, although sGC oxidation is increased in both groups.
      Collectively, our data demonstrate that an intact sGC/PDE5/PKG-dependent
      signaling pathway exists in RBCs, which remains fully responsive to NO and sGC
      stimulators/activators in patients with endothelial dysfunction. Targeting this
      pathway may be helpful in diseases with NO deficiency in the microcirculation
      like sickle cell anemia, pulmonary hypertension, and heart failure.

PMID- 29024898
TI  - Maternal and embryonic exposure to the water soluble fraction of crude oil or
      lead induces behavioral abnormalities in zebrafish (Danio rerio), and the
      mechanisms involved.
AB  - The water-soluble fraction (WSF) of crude oil plays an important role in the
      toxicity of crude oil in aquatic environments. Heavy metals, such as lead (Pb)
      are also important environmental contaminants, which can reach aquatic systems
      via the effluents of industrial, urban and mining sources. In the present study,
      we investigated whether maternal and embryonic exposure to the WSF (5, 50 MUg/L)
      or Pb (10, 100 MUg/L) could induce behavioral abnormalities in zebrafish. Our
      results showed that maternal and embryonic exposure to the WSF (5, 50 MUg/L) and
      Pb (10, 100 MUg/L) induced swimming activity alterations in larval and juvenile
      zebrafish. In 15 days post-fertilization (dpf) larval zebrafish, the distance
      moved was significantly increased in the groups treated with the WSF (5, 50
      MUg/L), but the angular velocity and turn angle were decreased after treatment
      with the WSF (5, 50 MUg/L) or Pb (10, 100 MUg/L). In 30 dpf juvenile zebrafish,
      the distance moved was markedly decreased in both groups treated with the WSF (5,
      50 MUg/L) and the Pb (10 MUg/L) group, but the percentage of zebrafish moving up
      and the inter-fish distance of two juvenile fish were increased after treatment
      with the WSF (5, 50 MUg/L) or Pb (10, 100 MUg/L). Maternal and embryonic exposure
      to the WSF (5, 50 MUg/L) or Pb (10, 100 MUg/L) likely impaired the brain neurons
      growth and induced behavioral abnormalities in the larval and juvenile zebrafish.
      Furthermore, the expressions of some key genes, which were associated with
      calcium channels, behavioral development or the metabolism of environmental
      contaminants, were changed.

PMID- 29024899
TI  - Mangiferin ameliorates fatty liver via modulation of autophagy and inflammation
      in high-fat-diet induced mice.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease
      globally. The progression of NAFLD is complex and associated with inflammation,
      oxidative stress, autophagy, endoplasmic reticulum stress, and insulin
      resistance. Mangiferin, a natural C-glucosyl xanthone, has been reported to show
      multiple biological activities. The aim of this study was to investigate the
      therapeutic effect of mangiferin on NAFLD and the underlying molecular mechanism.
      We established a mouse model of NAFLD using a high-fat diet (HFD), and injected
      the mice with different doses of mangiferin (15, 30, and 60mg/kg,
      intraperitoneal) for 12 weeks. Liver tissue was assessed to evaluate changes in
      inflammatory responses, autophagy, and glycolipid metabolism. We found that
      mangiferin decreased body weight, as well as the levels of triglycerides and
      total cholesterol in plasma and the liver. It also increased glucose tolerance in
      HFD-fed mice. In addition, mangiferin decreased inflammatory responses by
      inhibiting the activities of nuclear factor kappa B and c-Jun N-terminal kinase,
      regulated autophagy via the AMP-activated protein kinase/mechanistic target of
      rapamycin signaling pathway, and improved glycolipid metabolism via modulation of
      the insulin receptor substrate/phosphoinositide 3-kinase/protein kinase B
      signaling pathway. This study demonstrated that mangiferin significantly
      ameliorates NAFLD development in HFD-fed mice by inhibiting inflammatory
      responses, activating autophagy, and improving glycolipid metabolism.

PMID- 29024900
TI  - The associations between problematic Facebook use, psychological distress and
      well-being among adolescents and young adults: A systematic review and meta
      analysis.
AB  - BACKGROUND: A growing body of research has analyzed the potential risks of
      problematic Facebook use for mental health and well-being. The current meta
      analysis is the first to examine the associations between problematic Facebook
      use, psychological distress (i.e., depression, anxiety, etc.) and well-being
      (life satisfaction, positive mental health) among adolescents and young adults.
      METHOD: A comprehensive search strategy identified relevant studies in PsychInfo,
      Pubmed, Scopus, ResearchGate, and Google Scholar. RESULTS: The final sample
      included 23 independent samples with a total of 13,929 participants (60.7%
      females; Mage= 21.93, range: 16.5-32.4). Results of random effects meta-analysis
      confirmed a positive correlation between problematic Facebook use and
      psychological distress (r = .34, 95% CI [.28, .39]). Moderation analysis revealed
      that effect sizes were larger in older samples. Moreover, a negative correlation
      between problematic Facebook use and well-being was observed (r = -.22, 95% CI [
      .28, -.15]). LIMITATIONS: All available studies used a cross-sectional design
      thus hampering the possibility to establish the direction of the association
      between problematic Facebook use and psychological distress and well-being.
      CONCLUSIONS: Results are discussed within the extant literature on problematic
      Facebook use and future research directions are proposed. This research may also
      inform clinical and prevention interventions on problematic Facebook use.

PMID- 29024901
TI  - Impact of initial medication non-adherence to SSRIs on medical visits and sick
      leaves.
AB  - BACKGROUND: Initial medication non-adherence (IMNA) to antidepressants, which are
      commonly used to treat depression in primary care (PC), is around 6-12%. Although
      it is well known that post-initial non-adherence to antidepressants increases the
      cost of depression, the impact of IMNA on cost is unknown. The aim of this study
      is to assess the impact of IMNA to Selective Serotonin Reuptake Inhibitors (SSRI)
      on medical visits and sick leave in patients with depression treated in PC in
      Catalonia (Spain). METHODS: This was a four-year retrospective register-based
      study (2011-2014). All PC patients of working age who received a new SSRI
      prescription and had a diagnosis of depression were included (N = 79,642).
      Treatment initiation, number of visits and days on sick leave were gathered from
      the database. We assessed the impact of IMNA on costs with ordered logistic
      regressions. RESULTS: The 3-year incidence of IMNA was 15%. Initially non
      adherent patients made a lesser number of GP visits (OR = 0.82; 95% CI = 0.79
      0.84) but had more days on sick leave (OR = 1.25; 95% CI = 1.20-1.31). There were
      no differences in the number of specialist visits (OR = 1.04; 95% CI = 0.99
      1.08). LIMITATIONS: Differences between adherent and non-adherent patients could
      be explained by non-observed variables. GP recognition and documentation of
      depression might be inaccurate. Costs of unpaid work and use of hospital services
      were not considered. CONCLUSIONS: Although IMNA decreases the use of medical PC
      services, it increases the number of days on sick leave. This could also indicate
      worse health status. These consequences are currently overlooked when considering
      post-initial medication non-adherence.

PMID- 29024902
TI  - Psychological and behavioral characteristics of suicide attempts and non-suicidal
      self-injury in Chinese adolescents.
AB  - BACKGROUND: Suicide attempts (SA) and non-suicidal self-injury (NSSI) are
      prevalent in adolescents and important risk factors of suicide death. Both SA and
      NSSI are associated with multiple psychosocial, behavioral, biological and
      genetic factors. This study examined similarities and differences in
      psychological vulnerability and internalizing and externalizing problems between
      adolescents with SA and NSSI. METHODS: Participants consisted of 11,831 students
      and had a mean age of 14.97 (SD = 1.46) years. Students completed a structured
      questionnaire to report their demographic information, psychological
      characteristics, internalizing and externalizing problems, SA and NSSI. Based on
      the history of NSSI and SA in the last year, the sample was divided into four
      groups: non-self-harm (NSH), NSSI only, SA only, and NSSI+SA. Multivariate
      analyses of covariance and post-hoc pairwise comparisons were performed for
      multiple comparisons. RESULTS: Compared with NSH group, adolescents with either
      NSSI or SA scored significantly higher on trait anger, impulsiveness,
      hopelessness, internalizing and externalizing problems. NSSI+SA group and SA only
      group scored significantly higher than NSSI only group but both did not score
      significantly different on most psychological and behavioral variables.
      LIMITATIONS: Limitations include reliance on self-reported measures and cross
      sectional survey. CONCLUSIONS: Psychological and behavioral profiles between
      adolescents with SA and NSSI are similar but are more severe in suicide
      attempters. The findings highlight the necessity of assessing psychological and
      behavioral problems for prevention and early intervention of adolescent self
      harm.

PMID- 29024903
TI  - Bacteria, mould and yeast spore inactivation studies by scanning electron
      microscope observations.
AB  - Spores are the most resistant form of microbial cells, thus difficult to
      inactivate. The pathogenic or food spoilage effects of certain spore-forming
      microorganisms have been the primary basis of sterilization and pasteurization
      processes. Thermal sterilization is the most common method to inactivate spores
      present on medical equipment and foods. High pressure processing (HPP) is an
      emerging and commercial non-thermal food pasteurization technique. Although
      previous studies demonstrated the effectiveness of thermal and non-thermal spore
      inactivation, the in-depth mechanisms of spore inactivation are as yet unclear.
      Live and dead forms of two food spoilage bacteria, a mould and a yeast were
      examined using scanning electron microscopy before and after the inactivation
      treatment. Alicyclobacillus acidoterrestris and Geobacillus stearothermophilus
      bacteria are indicators of acidic foods pasteurization and sterilization
      processes, respectively. Neosartorya fischeri is a phyto-pathogenic mould
      attacking fruits. Saccharomyces cerevisiae is a yeast with various applications
      for winemaking, brewing, baking and the production of biofuel from crops (e.g.
      sugar cane). Spores of the four microbial species were thermally inactivated.
      Spores of S. cerevisiae were observed in the ascus and free form after thermal
      and HPP treatments. Different forms of damage and cell destruction were observed
      for each microbial spore. Thermal treatment inactivated bacterial spores of A.
      acidoterrestris and G. stearothermophilus by attacking the inner core of the
      spore. The heat first altered the membrane permeability allowing the release of
      intracellular components. Subsequently, hydration of spores, physicochemical
      modifications of proteins, flattening and formation of indentations occurred,
      with subsequent spore death. Regarding N. fischeri, thermal inactivation caused
      cell destruction and leakage of intracellular components. Both thermal and HPP
      treatments of S. cerevisiae free spores attacked the inner membrane, altering its
      permeability, and allowing in final stages the transfer of intracellular
      components to the outside. The spore destruction caused by thermal treatment was
      more severe than HPP, as HPP had less effect on the spore core. All injured
      spores have undergone irreversible volume and shape changes. While some of the
      leakage of spore contents is visible around the deformed but fully shaped spore,
      other spores exhibited large indentations and were completely deformed,
      apparently without any contents inside. This current study contributed to the
      understanding of spore inactivation by thermal and non-thermal processes.

PMID- 29024904
TI  - Salmonella survival during thermal dehydration of fresh garlic and storage of
      dehydrated garlic products.
AB  - Salmonella survival was characterized and modeled during thermal dehydration of
      fresh garlic and storage of dehydrated garlic products. In our experiments that
      simulated commercial dehydration processing at 80+/-5 degrees C, moderate level
      of Salmonella contamination (4-5logCFU/g) on fresh garlic was reduced below the
      enumeration limit (1.7logCFU/g) after 4.5h of dehydration and not detectable by
      culture enrichment after 7h. With high level of contamination (7-8logCFU/g), the
      Salmonella population persisted at 3.6logCFU/g after 8h of processing. By
      increasing the dehydration temperature to 90+/-5 degrees C, the moderate and high
      levels of initial Salmonella load on fresh garlic dropped below the enumeration
      limit after 1.5 and 3.75h of processing and became undetectable by culture
      enrichment after 2.5 and 6h, respectively. During the storage of dried garlic
      products, Salmonella was not able to grow under all tested combinations of
      temperature (25 and 35 degrees C) and water activity (0.56-0.98) levels,
      suggesting active inhibition. Storage temperature played a primary role in
      determining Salmonella survival on dehydrated garlic flakes. Under a typical
      storage condition at 25 degrees C and ambient relative humidity, Salmonella could
      persist over months with the population gradually declining (4.3 log reduction
      over 88days). Granular size of dehydrated garlic had an impact on Salmonella
      survival, with better survival of the pathogen observed in bigger granules. At
      the early stage of dehydrated garlic storage (until 7days), rising water activity
      appeared to initially promote but then inhibited Salmonella survival, resulting
      in a water activity threshold at 0.73 where Salmonella displayed strongest
      persistence. However, this phenomenon was less apparent during extended storage
      (after 14days).

PMID- 29024905
TI  - Hantavirus maintenance and transmission in reservoir host populations.
AB  - Hantaviruses are primarily hosted by mammalian species of the orders Rodentia,
      Eulipotyphla and Chiroptera. Spillover to humans is common, and understanding
      hantavirus maintenance and transmission in reservoir host populations is
      important for efforts to curtail human disease. Recent field research challenges
      traditional phases of virus shedding kinetics derived from laboratory rodent
      infection experiments. Organ infection sites in non-rodent hosts suggest similar
      transmission routes to rodents, but require direct assessment. Further advances
      have also been made in understanding virus persistence (and fadeouts) in
      fluctuating host populations, as well as occupational, recreational and
      environmental risk factors associated with spillover to humans. However, despite
      relevance for both intra-species and inter-species transmission, our
      understanding of the longevity of hantaviruses in natural environments remains
      limited.

PMID- 29024906
TI  - Walkability, complete streets, and gender: Who benefits most?
AB  - Does street walkability and a new complete street renovation relate to street use
      and gender composition? We audited two mixed-walkability complete streets
      ("complete less-urban" and "complete-urban"), one low-walkable street, and one
      high-walkable street at pre-renovation and twice post-renovation. Complete street
      users increased, especially for the complete-less urban street. Typically, the
      high-walkable street attracted the most and the low-walkable street attracted the
      fewest total people, males, and females; complete streets were in between. On
      blocks with people, females were only 29% of users; females were much less common
      on low- walkable streets. Street improvements might enhance gender equity.

PMID- 29024907
TI  - Relationship between the neighbourhood built environment and early child
      development.
AB  - The relationship between features of the neighbourhood built environment and
      early child development was investigated using area-level data from the
      Australian Early Development Census. Overall 9.0% of children were
      developmentally vulnerable on the Physical Health and Well-being domain, 8.1% on
      the Social Competence domain and 8.1% on the Emotional Maturity domain. After
      adjustment for socio-demographic factors, Local Communities with the highest
      quintile of home yard space had significantly lower odds of developmental
      vulnerability on the Emotional Maturity domain. Residing in a Local Community
      with fewer main roads was associated with a decrease in the proportion of
      children developmentally vulnerable on the Social Competence domain. Overall,
      sociodemographic factors were more important than aspects of the neighbourhood
      physical environment for explaining variation between Local Communities in the
      developmental vulnerability of children.

PMID- 29024908
TI  - Tackling the mortality from long-term exposure to outdoor air pollution in
      megacities: Lessons from the Greater Cairo case study.
AB  - OBJECTIVE: The poor outdoor air quality in megacities of the developing world and
      its impact on health is a matter of concern for both the local populations and
      the decision-makers. The objective of this work is to quantify the mortality
      attributable to long-term exposure to PM2.5, NO2, and O3 in Greater Cairo
      (Egypt). METHODS: We analyze the temporal and spatial variability of the three
      pollutants concentrations measured at 18 stations of the area. Then, we apply the
      method recommended by the WHO to estimate the excess mortality. In this
      assessment, three different shapes (log-linear, linear, and log-log) of the
      concentration-response functions (CRF) are used. RESULTS: With PM2.5
      concentrations varying from 50 to more than 100ug/m3 in the different sectors of
      the megacity, the spatial variability of this pollutant is found to be one
      important cause of uncertainty on the excess mortality associated with it. Also
      important is the choice of the CRF. With the average (75ug/m3) PM2.5
      concentration and the most favorable log-log shape of the CRF, 11% (CI, 9-14%) of
      the non-accidental mortality in the population older than 30 years can still be
      attributed to PM2.5, which corresponds to 12520 (CI, 10240-15930) yearly
      premature deaths. Should the Egyptian legal 70ug/m3 PM10 limit (corresponding to
      approximately 37.5ug/m3 for PM2.5) be met, this number would be reduced to 7970,
      meaning that 4550 premature deaths could be avoided each year. Except around some
      industrial or traffic hot spots, NO2 concentration is found to be below the
      40ug/m3 air quality guideline of the WHO. However, the average concentration
      (34ug/m3) of this gas exceeds the stricter 10ug/m3 recommendation of the HRAPIE
      project and it is thus estimated that from 7850 to 10470 yearly deaths can be
      attributed to NO2. Finally, with the ozone concentration measured at one station
      only, it is found that, depending on the choice of the CRF, between 2.4% and 8.8%
      of the mortality due to respiratory diseases can be attributed to this gas.
      CONCLUSION: In Greater Cairo, PM2.5 and NO2 constitute major health risks. The
      best estimate is that in the population older than 30 years, 11% and 8% of the
      non-accidental mortality can be attributed to these two pollutants, respectively.

PMID- 29024909
TI  - Impact of phosphate limitation on PHA production in a feast-famine process.
AB  - Double-limitation systems have shown to induce polyhydroxyalkanoates (PHA)
      production in chemostat studies limited in e.g. carbon and phosphate. In this
      work the impact of double substrate limitation on the enrichment of a PHA
      producing community was studied in a sequencing batch process. Enrichments at
      different C/P concentration ratios in the influent were established and the
      effect on the PHA production capacity and the enrichment community structure was
      investigated. Experimental results demonstrated that when a double substrate
      limitation is imposed at a C/P ratio in the influent in a range of 150 (C
      mol/mol), the P-content of the biomass and the specific substrate uptake rates
      decreased. Nonetheless, the PHA storage capacity remained high (with a maximum of
      84 wt%). At a C/P ratio of 300, competition in the microbial community is based
      on phosphate uptake, and the PHA production capacity is lost. Biomass specific
      substrate uptake rates are a linear function of the cellular P-content, offering
      advantages for scaling-up the PHA production process due to lower oxygen
      requirements.

PMID- 29024910
TI  - Leishmanicidal and cytotoxic activity of hederagenin-bistriazolyl derivatives.
AB  - Aiming to obtain new potent leishmanicidal and cytotoxic compounds from natural
      sources, the triterpene hederagenin was converted into several new 1,2,3
      triazolyl derivatives tethered at C-23 and C-28. For this work hederagenin was
      isolated from fruits of Sapindus saponaria and reacted with propargyl bromide to
      afford as a major product bis-propargylic derivative 1 in 74%. Submitting this
      compound to Huisgen 1,3-dipolar cycloaddition reactions with several azides
      afforded the derivatives 2-19 with yields in the range of 40-87%. All compounds
      have been screened for in vitro cytotoxic activity in a panel of five human
      cancer cell lines by a SRB assay. The bioassays showed that compound 19 was the
      most cytotoxic against all human cancer cell lines with EC50 = 7.4-12.1 MUM.
      Moreover, leishmanicidal activity was evaluated through the in vitro effect in
      the growth of Leishmania infantum, and derivatives 1, 2, 5 and 17 were highly
      effective preventing proliferation of intracellular amastigote forms of L.
      infantum (IC50 = 28.8, 25.9, 5.6 and 7.4 MUM, respectively). All these compounds
      showed a higher selectivity index and low toxicity against two strains of kidney
      BGM and liver HepG2 cells. Compound 5 has higher selectivity (1780 times) in
      comparison with the commercial antimony drug and is around 8 times more selective
      than the most active compound previously reported hederagenin derivative. Such
      high activity associated with low toxicities make the new bis-traiazolyl
      derivatives promising candidates for the treatment of leishmaniasis. In addition,
      hederagenin and some derivatives (2, 5 and 17) showed interaction in the binding
      site of the enzyme CYP51Li.

PMID- 29024911
TI  - Simultaneous quantitative analysis of uremic toxins by LC-MS/MS with a reversed
      phase/cation-exchange/anion-exchange tri-modal mixed-mode column.
AB  - Column choice is crucial to the development of liquid chromatography/tandem mass
      spectrometry (LC-MS/MS) methods because analyte selectivity is dependent on the
      nature of the stationary phase. Recently, mixed-mode chromatography, which
      employs a combination of two or more stationary phases and solvent systems, has
      emerged as an alternative to multiple, complementary, single-column systems. This
      report describes the development and validation of a novel analytical method
      based on LC-MS/MS employing a reversed-phase/cation-exchange/anion-exchange tri
      modal column (Scherzo SS-C18; Imtakt) for the simultaneous quantification of
      various uremic toxins (UTx), including creatinine, 1-methyladenosine,
      trimethylamine-N-oxide, indoxyl sulfate, p-cresyl sulfate, phenyl sulfate and 4
      ethylphenyl sulfate. Stable isotope-labeled compounds were prepared as internal
      standards (ISs) for each analyte. Mobile phase optimization and appropriate
      gradient conditions resulted in satisfactory retention and peak resolution that
      could not have been attained with a single stationary phase LC system. The
      essential validation parameters, including intra- and inter-assay precision and
      accuracy, were adequate. The validated method was applied to measure serum levels
      of the aforementioned compounds in 19 patients with chronic kidney disease. This
      is the first report detailing the simultaneous quantification of these analytes
      using stable isotopes as ISs. Our results suggest that Scherzo SS-C18 columns
      will be considered breakthrough tools in the development of analytical methods
      for compounds that are difficult to quantify simultaneously in traditional LC
      systems.

PMID- 29024912
TI  - How important is aspirin adherence when evaluating effectiveness of low-dose
      aspirin?
AB  - Low-dose aspirin (LDA) is advocated for women at high-risk of pre-eclampsia,
      providing a modest, 10%, reduction in risk. Cardiology meta-analyses demonstrate
      18% reduction in serious vascular events with LDA. Non-responsiveness to aspirin
      (sometimes termed aspirin resistance) and variable clinical effectiveness are
      often attributed to suboptimal adherence. The aim of this review was to identify
      the scope of adherence assessments in RCTs evaluating aspirin effectiveness in
      cardiology and obstetrics and discuss the quality of information provided by
      current methods. We searched MEDLINE, EMBASE and the Cochrane Library, limited to
      humans and English language, for RCTs evaluating aspirin in cardiology; 14/03/13
      13/03/16 and pregnancy 1957-13/03/16. Search terms; 'aspirin', 'acetylsalicylic
      acid' appearing adjacent to 'myocardial infarction' or 'pregnancy', 'pregnant',
      'obstetric' were used. 38% (25/68) of obstetric and 32% (20/62) of cardiology
      RCTs assessed aspirin adherence and 24% (6/25) and 29% (6/21) of obstetric and
      cardiology RCTs, respectively, defined acceptable adherence. Semi-quantitative
      methods (pill counts, medication weighing) prevailed in obstetric RCTs (93%),
      qualitative methods (interviews, questionnaires) were more frequent in obstetrics
      (67%). Two obstetric RCTs quantified serum thromboxane B2 and salicylic acid, but
      no quantitative methods were used in cardiology Aspirin has proven efficacy, but
      suboptimal adherence is widespread and difficult to accurately quantify. Little
      is currently known about aspirin adherence in pregnancy. RCTs evaluating aspirin
      effectiveness show over-reliance on qualitative adherence assessments vulnerable
      to inherent inaccuracies. Reliable adherence data is important to assess and
      optimise the clinical effectiveness of LDA. We propose that adherence should be
      formally assessed in future trials and that development of quantitative
      assessments may prove valuable for trial protocols.

PMID- 29024913
TI  - Retrospective study on de novo postoperative urinary incontinence after pelvic
      organ prolapse surgery.
AB  - OBJECTIVE: Reported incidences of de novo urinary incontinence (UI) following
      pelvic organ prolapse (POP) surgery in preoperatively continent women vary
      between 2% and 43%. The aim of this study was to investigate the incidence and
      the types of de novo UI and differences between operations in different
      compartments. STUDY DESIGN: Retrospective study of 678 women with POP surgery
      using native tissue repair during a 3-year period. Patients completed three
      modified prolapse questions from the International Consultation on Incontinence
      Vaginal Symptoms (ICIQ-VS) and the International Consultation on Incontinence
      Questionnaire- Urinary Incontinence Short Form (ICIQ-UI SF) before undergoing
      surgery and 3 months postoperatively. Patients who were totally dry and scored 0
      on ICIQ-UI SF before surgery were included in the study (N=299). The patients
      developing new onset UI on ICIQ-UI SF postoperatively were interviewed by
      telephone after median 30 months. RESULTS: A total of 33 patients (11%) developed
      subjective de novo UI at 3 months follow-up. The majority of patients (N=16)
      reported stress UI. The risk of developing de novo UI increased with parity
      (p=0.03). We found no difference between operations in different compartments. At
      long-term follow-up 12 patients became continent without incontinence surgery or
      medical treatment leaving only 21 patients (7%) incontinent. CONCLUSION: The risk
      of developing de novo UI after prolapse surgery with native tissue repair is low
      and improves over time. Parity is significantly associated with the risk of
      developing de novo UI. There is no difference in the incidence of de novo
      incontinence between operations in different compartments.

PMID- 29024914
TI  - 'Exploring' the regulation of Streptomyces growth and development.
AB  - The Streptomyces life cycle encompasses three well-established developmental
      stages: vegetative hyphae, aerial hyphae and spores. Many regulators governing
      the transitions between these life cycle stages have been identified, and recent
      work is shedding light on their specific functions. A new discovery has shown
      Streptomyces can deviate from this classic life cycle through a process termed
      'exploration', where cells rapidly traverse solid surfaces. Exploration does not
      require any of the traditional developmental regulators, and therefore provides
      an exciting new context in which to uncover novel developmental pathways. Here,
      we summarize our understanding of how Streptomyces exploration is controlled, and
      we speculate on how insight into classical regulation and stress response systems
      can inform future research into the regulation of exploratory growth.

PMID- 29024915
TI  - Information density converges in dialogue: Towards an information-theoretic
      model.
AB  - The principle of entropy rate constancy (ERC) states that language users
      distribute information such that words tend to be equally predictable given
      previous contexts. We examine the applicability of this principle to spoken
      dialogue, as previous findings primarily rest on written text. The study takes
      into account the joint-activity nature of dialogue and the topic shift mechanisms
      that are different from monologue. It examines how the information contributions
      from the two dialogue partners interactively evolve as the discourse develops.
      The increase of local sentence-level information density (predicted by ERC) is
      shown to apply to dialogue overall. However, when the different roles of
      interlocutors in introducing new topics are identified, their contribution in
      information content displays a new converging pattern. We draw explanations to
      this pattern from multiple perspectives: Casting dialogue as an information
      exchange system would mean that the pattern is the result of two interlocutors
      maintaining their own context rather than sharing one. Second, we present some
      empirical evidence that a model of Interactive Alignment may include information
      density to explain the effect. Third, we argue that building common ground is a
      process analogous to information convergence. Thus, we put forward an information
      theoretic view of dialogue, under which some existing theories of human dialogue
      may eventually be unified.

PMID- 29024916
TI  - Can monolinguals be like bilinguals? Evidence from dialect switching.
AB  - Bilinguals rely on cognitive control mechanisms like selective activation and
      inhibition of lexical entries to prevent intrusions from the non-target language.
      We present cross-linguistic evidence that these mechanisms also operate in
      bidialectals. Thirty-two native German speakers who sometimes use the Ocher Platt
      dialect, and thirty-two native English speakers who sometimes use the Dundonian
      Scots dialect completed a dialect-switching task. Naming latencies were higher
      for switch than for non-switch trials, and lower for cognate compared to non
      cognate nouns. Switch costs were symmetrical, regardless of whether participants
      actively used the dialect or not. In contrast, sixteen monodialectal English
      speakers, who performed the dialect-switching task after being trained on the
      Dundonian words, showed asymmetrical switch costs with longer latencies when
      switching back into Standard English. These results are reminiscent of findings
      for balanced vs. unbalanced bilinguals, and suggest that monolingual dialect
      speakers can recruit control mechanisms in similar ways as bilinguals.

PMID- 29024917
TI  - Thermo-responsive mesoporous silica/lipid bilayer hybrid nanoparticles for
      doxorubicin on-demand delivery and reduced premature release.
AB  - Hybrid nanocarriers based on mesoporous silica nanoparticles (MSNs) and supported
      lipid bilayer (SLB) have been studied as drug delivery system. It still remains
      challenges to develop these nanocarriers (SLB-MSNs) with on-demand drug release
      profile for chemotherapy. Here, we reported the biocompatible SLB-MSNs with high
      drug loading, which could release doxorubicin (DOX) in response to hyperthermia
      and reduce premature release. After synthesis of MSNs via a sol-gel procedure,
      the thermo-responsive SLB was deposited on the MSNs by sonication to completely
      seal the mesopores. The obtained SLB-MSNs consisted of 50 nm-sized MSN cores and
      6.3 nm-thick SLB shells. Due to the big surface and pore volume of MSNs, the high
      drug loading content (7.30+/-0.02%) and encapsulation efficiency (91.16+/-0.28%)
      were achieved. The SLB blocking the mesopores reduced 50% of premature release
      and achieved on-demand release in a thermo-responsive manner. Moreover, SLB-MSNs
      showed good hemocompatibility at any tested concentration (25-700MUg/mL), while
      bare MSNs caused 100% of hemolysis at concentration larger than 325MUg/mL. In
      addition, in vitro U251 cell uptake experiment demonstrated that compared with
      uncapped MSNs, SLB-MSNs could prevent untargeted cellular uptake of DOX owing to
      reduced premature release and steric hindrance of PEG, which would be beneficial
      to minimize toxicity for healthy tissues. These results indicated that SLB-MSNs
      with thermo-responsive release capacity possessed great potential in future
      synergistic thermo-chemotherapy.

PMID- 29024918
TI  - Design of parenteral MNP-loaded PLGA nanoparticles by a low-energy emulsification
      approach as theragnostic platforms for intravenous or intratumoral
      administration.
AB  - Encapsulation of magnetic nanoparticles (MNP) into PLGA nanoparticles has been
      achieved by nano-emulsion templating using for the first time both, a low-energy
      emulsification method as well as biocompatible components accepted for
      pharmaceuticals intended for human use. The incorporation of MNP by nano-emulsion
      templating method proposed in this work has been investigated in two different
      systems applying mild process conditions and is shown to be simple and versatile,
      providing stable MNP-loaded PLGA nanoparticles with tunable size and MNP
      concentration. MNP-loaded PLGA nanoparticles showed sizes below 200nm by DLS and
      50nm by TEM, and mean MNP loading per PLGA nanoparticle of 1 to 4, depending on
      the nanoparticle dispersion composition. Physical-chemical features suggest that
      the MNP-loaded PLGA nanoparticles obtained are good candidates for intravenous or
      intratumoral administration.

PMID- 29024919
TI  - Graphene oxide@gold nanorods for chemo-photothermal treatment and controlled
      release of doxorubicin in mice Tumor.
AB  - Graphene oxide (GO) is a close derivative of graphene has unlocked many pivotal
      steps in drug delivery due to their inherent biocompatibility, excellent drug
      loading capacity, and shows antibacterial, antifungal properties etc. We used a
      novel plant material called Gum arabic (GA) to increase the solubility of GO as
      well as to chemically reduce it in the solution. GA functionalized GO (fGO)
      exhibited increased absorption in near infra-red region (NIR) which was exploited
      in photothermal therapy for cancer. In order to understand the shape and size
      effect of GO which may affect their rheological properties, we have conjugated
      them with gold nanorods (GNRs) using in situ synthesis of GO@GNRs via seed
      mediated method. To the above conjugate, Doxorubicin (DOX) was attached at
      ambient temperature (28+/-2 degrees C). The release kinetics of DOX with the
      effect of NIR exposure was also carefully studied via in vitro photothermal
      killing of A549 cell lines. The enhancement in NIR induced drug release and
      photothermal property was observed which indicates that the fGO@GNRs-DOX method
      is an ideal choice for chemotherapy and photothermal therapy simultaneously.

PMID- 29024920
TI  - Chitosan/hydroxyapatite (HA)/hydroxypropylmethyl cellulose (HPMC) spongy
      scaffolds-synthesis and evaluation as potential alveolar bone substitutes.
AB  - Alveolar bone loss is associated with infections and its augmentation is a pre
      requisite for the success of dental implants. In present study, we aim to develop
      and evaluate novel freeze dried doxycycline loaded chitosan (CS)/hydroxyapatite
      (HA) spongy scaffolds where hydroxypropylmethyl cellulose (HPMC) was added as a
      crosslinker. Scaffolds displayed compressive strength of 14MPa/cm3 and 0.34 as
      elastic response. The interconnected pore diameter was 41-273MUm, favorably
      provided the template supporting cells and transport. An overall 10% degradation
      was seen after 14day's studies at pH 7.4 in PBS. Doxycycline hyclate, a
      frequently used drug to counter oral infections, demonstrated an initial burst
      release (6-8h), followed by a sustain release profile for the remaining 64h.
      CS/HA/HPMC scaffolds were nontoxic and promoted pre-osteoblast cell viability as
      seen with live/dead calcein staining after 24h where scaffolds with 10% and 25%
      HPMC by weight of scaffold had more viable cells. Scaffolds with 10%, 20% and 25%
      HPMC by weight of scaffold showed efficient cellular adhesion as seen in scanning
      electron microscopy images (day 8) indicating that pre-osteoblast cells were able
      to adhere well on the surface and into the porous structure via cytoplasmic
      extensions. Hoechst 33258 nuclear staining at day 2 and 8 indicated cell
      proliferation which was further supported byMTT assay at day 2, 4 and 8. Although
      all scaffolds supported pre-osteoblast cell viability, alkaline phosphatase (ALP)
      staining demonstrated that upon induction, differentiation was pronounced in case
      of scaffolds with 10% HMPC scaffolds. Conclusively, these materials having all
      the required mechanical and biological properties are potential candidates for
      alveolar bone regeneration.

PMID- 29024921
TI  - Highly sensitive and selective sensor for sunset yellow based on molecularly
      imprinted polydopamine-coated multi-walled carbon nanotubes.
AB  - Polydopamine (PDA) can be formed by monomeric self-polymerization in water. This
      convenient behavior was exploited to prepare a molecularly imprinted polymer
      (MIP) layer on the surface of multi-walled carbon nanotubes (MWCNTs) with sunset
      yellow (SY) as a template molecule. The prepared nanocomposites were
      characterized, and their electrochemical behavior towards SY was investigated.
      Under the optimized conditions, a glassy carbon electrode modified with the
      imprinted nanocomposite showed a highly selective and ultrasensitive
      electrochemical response to SY compared with the performance of control
      electrodes and previously reported electrochemical sensors for SY. The improved
      behavior of the developed sensor can be attributed to its superficial highly
      matched imprinted cavities on the excellent electrocatalytic matrix of MWCNTs and
      the electronic barrier of the non-imprinted PDA to outside molecules. The
      fabricated sensor expressed a linear relationship to SY concentrations from 2.2nM
      to 4.64MUM with a detection limit of 1.4nM (S/N = 3). The sensor also exhibited
      excellent selectivity for SY over its structural analogs, good stability, and
      adequate reproducibility. The prepared sensor was successfully used to detect SY
      in real spiked samples. This methodology has potential application value and may
      be readily adapted to design other PDA-based MIP sensors.

PMID- 29024922
TI  - Isolation and whole genome analysis of endospore-forming bacteria from heroin.
AB  - Infections caused by endospore-forming bacteria have been associated with severe
      illness and death among persons who inject drugs. Analysis of the bacteria
      residing in heroin has thus been biased towards species that affect human health.
      Similarly, exploration of the bacterial diversity of seized street market heroin
      correlated with the skin microflora of recreational heroin users insofar as
      different Staphylococus spp. or typical environmental endospore formers including
      Bacillus cereus and other Bacilli outside the B. cereus sensu lato group as well
      as diverse Clostridia were identified. In this work 82 samples of non-street
      market ("wholesale") heroin originating from the German Federal Criminal Police
      Office's heroin analysis program seized during the period between 2009 and 2014
      were analyzed for contaminating bacteria. Without contact with the end user and
      with only little contaminations introduced by final processing, adulteration and
      cutting this heroin likely harbors original microbiota from the drug's original
      source or trafficking route. We found this drug to be only sparsely populated
      with retrievable heterotrophic, aerobic bacteria. In total, 68 isolates were
      retrieved from 49 out of 82 samples analyzed (60% culture positive). All isolates
      were endospore-forming, Gram-positive Bacilli. Completely absent were non
      endospore-formers or Gram-negatives. The three most predominant species were
      Bacillus clausii, Bacillus (para)licheniformis, and Terribacillus saccharophilus.
      Whole genome sequencing of these 68 isolates was performed using Illumina
      technology. Sequence data sets were assembled and annotated using an automated
      bioinformatics pipeline. Average nucleotide identity (ANI) values were calculated
      for all draft genomes and all close to identical genomes (ANI>99.5%) were
      compared to the forensic data of the seized drug, showing positive correlations
      that strongly warrant further research on this subject.

PMID- 29024924
TI  - Assessing heteroplasmic variant drift in the mtDNA control region of human hairs
      using an MPS approach.
AB  - Resolution of mitochondrial (mt) DNA heteroplasmy is possible when applying a
      massively parallel sequencing (MPS) approach. However, interpretation criteria
      for matching heteroplasmic sequences will need to be established that address a
      number of important topics, including the drift of variants in sample types such
      as human hair shafts. Prior to MPS analysis, we compared three different DNA
      extraction methods for hair using a custom mtDNA quantitative PCR (mtqPCR) assay,
      and found that a method involving bead capture significantly outperformed methods
      currently in place in forensic laboratories. The findings were similar for both
      fine (head) and coarse (pubic) hairs. Using the favored DNA extraction approach,
      hair shaft extracts were subjected to MPS analysis to assess heteroplasmic drift
      and the potential impact of the observations on interpretation of mtDNA MPS data.
      Hairs from different regions of the head were evaluated in individuals with
      varying percentages of heteroplasmy (low-level, high-level, and no detectable
      heteroplasmy), as measured in buccal and blood cells. The range of variant ratios
      was broad and was not significantly different between individuals in the low and
      high-level groups. While the range was also broad for the group of individuals
      with no heteroplasmy, the vast majority of hairs from these donors still
      exhibited a lack of heteroplasmy. A model was developed to predict the amount of
      heteroplasmy expected in hair samples when knowledge of the percentage of
      heteroplasmy in buccal cells is available. While significant, the model was best
      applied when levels of heteroplasmy in buccal cells was high. No correlation was
      observed between rates of heteroplasmy in blood cells and the predicted amount of
      heteroplasmy in hairs. Of particular interest, unexpected sites of mixed mtDNA
      sequence that could be interpreted as heteroplasmy were observed for 13% of the
      75 hairs tested. These sites can be explained as heteroplasmy not observed in
      buccal or blood cells, or sites of DNA damage, with inherent heteroplasmy a
      likely cause, possibly due to de novo mutation events. Overall, when applying an
      MPS approach to hair analysis, heteroplasmic variant ratios may be quite
      different than those observed in blood cells, may be correlated to rates in
      buccal cells, and may include unexpected mixed sites. The results of this study
      directly impact MPS analysis of minor sequence variants from hair samples, and
      are particularly relevant to clinical and forensic investigations.

PMID- 29024926
TI  - Metsovo Lung: A Story of Episteme, Techne, and Phronesis.

PMID- 29024923
TI  - A GHEP-ISFG collaborative study on the genetic variation of 38 autosomal indels
      for human identification in different continental populations.
AB  - A collaborative effort was carried out by the Spanish and Portuguese Speaking
      Working Group of the International Society for Forensic Genetics (GHEP-ISFG) to
      promote knowledge exchange between associate laboratories interested in the
      implementation of indel-based methodologies and build allele frequency databases
      of 38 indels for forensic applications. These databases include populations from
      different countries that are relevant for identification and kinship
      investigations undertaken by the participating laboratories. Before compiling
      population data, participants were asked to type the 38 indels in blind samples
      from annual GHEP-ISFG proficiency tests, using an amplification protocol
      previously described. Only laboratories that reported correct results contributed
      with population data to this study. A total of 5839 samples were genotyped from
      45 different populations from Africa, America, East Asia, Europe and Middle East.
      Population differentiation analysis showed significant differences between most
      populations studied from Africa and America, as well as between two Asian
      populations from China and East Timor. Low FST values were detected among most
      European populations. Overall diversities and parameters of forensic efficiency
      were high in populations from all continents.

PMID- 29024925
TI  - Defining functioning levels in patients with schizophrenia: A combination of a
      novel clustering method and brain SPECT analysis.
AB  - This study aims to define functioning levels of patients with schizophrenia by
      using a method of interpretable clustering based on a specific functioning scale,
      the Functional Remission Of General Schizophrenia (FROGS) scale, and to test
      their validity regarding clinical and neuroimaging characterization. In this
      observational study, patients with schizophrenia have been classified using a
      hierarchical top-down method called clustering using unsupervised binary trees
      (CUBT). Socio-demographic, clinical, and neuroimaging SPECT perfusion data were
      compared between the different clusters to ensure their clinical relevance. A
      total of 242 patients were analyzed. A four-group functioning level structure has
      been identified: 54 are classified as "minimal", 81 as "low", 64 as "moderate",
      and 43 as "high". The clustering shows satisfactory statistical properties,
      including reproducibility and discriminancy. The 4 clusters consistently
      differentiate patients. "High" functioning level patients reported significantly
      the lowest scores on the PANSS and the CDSS, and the highest scores on the GAF,
      the MARS and S-QoL 18. Functioning levels were significantly associated with
      cerebral perfusion of two relevant areas: the left inferior parietal cortex and
      the anterior cingulate. Our study provides relevant functioning levels in
      schizophrenia, and may enhance the use of functioning scale.

PMID- 29024927
TI  - Identifying a Potential Summary Measure for Overall Caries Level in Children
      Examined with the International Caries Detection and Assessment System.
AB  - OBJECTIVE: To identify a potential summative summary measure that reflects a
      patient's overall caries level in children examined with the International Caries
      Detection and Assessment System (ICDAS). SUBJECTS AND METHODS: Participants were
      1- to 15-year-old children from Kuwait, Brazil, and Spain. Children's teeth were
      examined using the ICDAS. Multiple measures of central tendency and dentition
      specific indices were considered as potential summative measures. The
      relationship between the summative measures and number of caries lesions was
      evaluated considering degrees of caries severity using Spearman's correlation
      analysis. The results were generated using the Kuwaiti sample and were cross
      validated using the Brazilian and Spanish samples. RESULTS: A total of 2,808
      children participated in the present study. Total ICDAS score and mean ICDAS
      score showed a strong correlation with the number of caries lesions at different
      caries severity levels in primary, mixed, and permanent dentitions. The total
      ICDAS score of 51 buccal (B), 61B, 54 occlusal (O), 55O, 64O, 65O, 74O, 75O, 84O,
      and 85O surfaces in primary dentition and the total ICDAS score of 14O, 16
      lingual (L), 16O, 24O, 26L, 26O, 36B, 36O, 37O, 46O, 46B, and 47O surfaces in
      permanent dentition or mixed dentition (if present) showed strong correlations
      with the number of caries lesions at different caries severity levels.
      CONCLUSIONS: Total ICDAS and mean ICDAS scores were the best summary measures of
      overall caries level at different dental stages. Total ICDAS scores of
      selectively examined 10 surfaces in primary dentition and 12 surfaces in
      permanent dentition can give an excellent summary measure for a patient's overall
      caries level with high diagnostic accuracy.

PMID- 29024928
TI  - Zinc Inhibits Collagenolysis by Cathepsin K and Matrix Metalloproteinases in
      Demineralized Dentin Matrix.
AB  - The enzymatic degradation of dentin organic matrix occurs via both the action of
      matrix metalloproteinases (MMPs) and cysteine cathepsins (CCs). Zinc can prevent
      collagen hydrolysis by MMPs. However, its effect on the activity of dentin-bound
      CCs is not known. The aim of this study was to investigate the effect of zinc on
      matrix-bound cathepsin K and MMP activity in dentin. Completely demineralized
      dentin beams were divided into test groups (n = 9) and incubated at 37 degrees C
      in an incubation media (1 mL) containing ZnCl2 of 0.02 (physiological level,
      control), 0.2, 0.5, 1, 5, 10, 20, 30, or 40 mM. The dry mass changes of the beams
      were determined, and incubation media were analyzed for cathepsin K- and MMP
      specific collagen degradation end products - CTX (C-terminal cross-linked
      telopeptide of type I collagen) and ICTP (cross-linked carboxy-terminal
      telopeptide of type I collagen) - at 1, 3, and 7 days of incubation. The mass
      loss of the beams decreased when the zinc level in the incubation media was >=5
      mM (p < 0.05). The release of liberated collagen degradation telopeptides
      decreased in accordance with the decrease in the mass loss rates of the beams.
      Cathepsin K-induced dentin collagen degradation can be strongly inhibited by
      zinc. Zinc levels of >=5 mM can be considered as a reliable threshold for the
      stabilization of dentin matrices.

PMID- 29024929
TI  - Inhibition of MicroRNA-21-5p Promotes the Radiation Sensitivity of Non-Small Cell
      Lung Cancer Through HMSH2.
AB  - BACKGROUND: This study aimed to explore the effects of microRNA-21-5p (miR-21-5p)
      on the radiation sensitivity of non-small cell lung cancer (NSCLC) and the
      involvement of human MutS homolog 2 (hMSH2) One hundred fourteen NSCLC patients
      at stage II or III who received surgery and postoperative radiotherapy were
      enrolled in this study. METHODS: The patients were assigned into radiation
      sensitive and -insensitive groups. NSCLC A549 cells were transfected to generate
      control, Negative control (NC), miR-21-5p inhibitor, miR-21-5p mimic, small
      interfering hMSH2 (sihMSH2), miR-21-5p inhibitor + sihMSH2 and hMSH2
      overexpression groups. Immunohistochemistry was performed to detect the hMSH2
      expression in transfected and irradiated cells. Quantitative real-time polymerase
      chain reaction (qRT-PCR) and western blotting were performed to evaluate A549 miR
      21-5p and hMSH2 expression in transfected and irradiated cells. A colony
      formation assay was adopted for cell survival analysis. The relationship between
      miR-21-5p and hMSH2 was verified by a luciferase reporter assay. Cell viability
      was measured by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide) assay, and apoptosis was assessed by flow cytometry. NSCLC nude mouse
      models were established, and tumor volumes and tumor weights were recorded.
      RESULTS: The radiation-sensitive group of patients exhibited lower miR-21-5p but
      higher hMSH2 expression than the insensitive group. For irradiated A549 cells,
      lower cell survival, higher apoptosis, increased miR-21-5p expression and
      decreased hMSH2 expression were observed at 6 and 8 Gy than at 0, 2 and 4 Gy;
      compared to 6 Gy, cell survival and hMSH2 expression were decreased and apoptosis
      and miR-21-5p expression were increased at 8 Gy. Additionally, miR-21-5p was
      found to target hMSH2. Compared with the control group, the cell survival rate
      was lower and the apoptosis rate higher in the miR-21-5p inhibitor group, whereas
      the opposite was observed for the miR-21-5p mimic and sihMSH2 groups. For the
      mouse model, decreased tumor volume and tumor weight and higher hMSH2 expression
      were found in the miR-21-5p inhibitor, radiation, hMSH2 overexpression, miR-21-5p
      inhibitor + radiation and hMSH2 overexpression + radiation groups compared with
      the control group. In addition, tumor volume and tumor weight were decreased and
      hMSH2 expression increased in the miR-21-5p inhibitor + radiation and hMSH2
      overexpression + radiation groups compared with the radiation alone group.
      CONCLUSION: These findings indicate that inhibition of miR-21 can promote the
      radiation sensitivity of NSCLC by targeting hMSH2.

PMID- 29024932
TI  - IUNS. 21st International Congress of Nutrition. Buenos Aires, Argentina, October
      15-20, 2017: Abstracts.

PMID- 29024930
TI  - Effect of Concurrent Src Kinase Inhibition with Short-Duration Hypothermia on
      Ca2+/Calmodulin Kinase IV Activity and Neuropathology after Hypoxia-Ischemia in
      the Newborn Swine Brain.
AB  - BACKGROUND: Hypoxia-ischemia (HI) results in increased activation of
      Ca2+/calmodulin kinase IV (CaM kinase IV) mediated by Src kinase. Therapeutic
      hypothermia ameliorates neuronal injury in the newborn. HYPOTHESIS: Inhibition of
      Src kinase concurrently with hypothermia further attenuates the hypoxia-induced
      increased activation of CaM kinase IV compared with hypothermia alone.
      DESIGN/METHODS: Ventilated piglets were exposed to HI, received saline or a
      selective Src kinase inhibitor (PP2), and were cooled to 33 degrees C.
      Neuropathology, adenosine triphosphate (ATP) and phosphocreatine (PCr)
      concentrations, and CaM kinase IV activity were determined. RESULTS: The
      neuropathology mean score (mean +/- SD) was 0.4 +/- 0.43 in normoxia-normothermia
      (p < 0.05 vs. hypoxia-normothermia), 3.5 +/- 0.89 in hypoxia-normothermia (p <
      0.05 vs. normoxia-normothermia), 0.7 +/- 0.73 in hypoxia-hypothermia (p < 0.05
      vs. normoxia-normothermia), and 0.5 +/- 0.70 in normoxia-hypothermia (p < 0.05
      vs. hypoxia-normothermia). The CaM kinase IV activity in cerebral tissue (pmol
      Pi/mg protein/min; mean +/- SD) was 2,002 +/- 729 in normoxia-normothermia, 1,704
      +/- 18 in normoxia-hypothermia, 6,017 +/- 2,510 in hypoxia-normothermia, 4,104 +/
      542 in hypoxia-hypothermia (p < 0.05 vs. normoxia-hypothermia), and 2,165 +/-
      415 in hypoxia-hypothermia with PP2 (p < 0.05 vs. hypoxia-hypothermia). The
      hypoxic groups with and without hypothermia or Src kinase inhibitor were
      comparable in the levels of ATP and PCr, indicating that they were similar in
      their degree of energy failure prior to treatments. Hypothermia or Src kinase
      inhibitor (PP2) did not restore the ATP and PCr levels. CONCLUSIONS: Hypothermia
      and Src kinase inhibition attenuated apoptotic cell death and improved
      neuropathology after hypoxia. The combination of short-duration hypothermia with
      Src kinase inhibition following hypoxia further attenuates the increased
      activation of CaM kinase IV compared to hypothermia alone in the newborn swine
      brain.

PMID- 29024931
TI  - Brain Metastases from Biliary Tract Cancer: A Monocentric Retrospective Analysis
      of 450 Patients.
AB  - OBJECTIVE: Brain metastases (BMs) from biliary tract cancer (BTC) are extremely
      rare. The aim of our study was to report the incidence of BMs in patients with
      BTC. METHODS: We retrospectively analyzed a series of 450 patients with BTC.
      Presence of brain lesions was investigated only when symptoms were evident.
      Cumulative incidence, median overall survival (OS) from detection of BMs, median
      OS from cancer diagnosis, and median time from cancer diagnosis to detection of
      BMs were evaluated. RESULTS: In our series, 6 patients developed BMs with an
      incidence of about 1.4%. Median OS from detection of BMs and from cancer
      diagnosis was, respectively, 3.7 (0.9-17.8) and 23 (9.9-57.6) months. Median time
      between cancer diagnosis and detection of BMs was 13.6 (7.3-52.8) months.
      Moreover, we observed a significant association between BMs and bone metastases
      (particularly vertebral lesions). DISCUSSION: Despite the retrospective design,
      this is the first study evaluating the incidence of BMs among patients with BTC
      in Western countries. BMs from BTC remain atypical, although their incidence is
      probably a little higher than previously assumed. Patients with BMs had poor
      prognosis. Unpredictably, bone involvement occurred in 5 out of 6 patients.

PMID- 29024933
TI  - Erratum.

PMID- 29024934
TI  - The Relationship between Vitamin D and Type 2 Diabetes Is Intriguing: Glimpses
      from the Spect-China Study.
AB  - OBJECTIVE: Vitamin D is a multifunctional vitamin for our body. Type 2 diabetes
      mellitus (T2DM) is a common metabolic disease. Whether T2DM affects the serum
      25(OH)D level has not been reported. The objective of this study was to reveal
      the extent to which vitamin D is present in the population in East China and to
      explore the relationship between serum 25(OH)D and T2DM. METHODS: The cohort was
      selected based on a large investigation named Survey on Prevalence in East China
      including 12,702 participants aged 21-92 years old. All the participants
      completed the questionnaire and went through a physical examination. Fasting
      blood samples were collected to test serum 25(OH)D and other metabolism-related
      indicators. AVONA was used to test the significance of differences among groups.
      Multinomial logistic regression was used to assess the association of T2DM with
      serum 25(OH)D level. RESULTS: The overall percentage of vitamin D deficiency was
      80.55% (male 74.1%, female 85.0%). Men with lower serum 25(OH)D level had high
      value in homeostasis model assessment of insulin resistance and HbA1c. The serum
      25(OH)D level of those who were diagnosed with T2DM was higher than that in non
      diabetics. The serum 25(OH)D level of pre-diabetes was the highest. T2DM patients
      trended to have higher serum 25(OH)D levels. CONCLUSION: Vitamin D deficiency is
      common among the people in East-China. T2DM patients had higher levels of serum
      25(OH)D. The relationship between vitamin D and T2DM is intriguing. It seemed
      that vitamin D was either irrelevant directly to T2DM or resisted in T2DM
      patients.

PMID- 29024935
TI  - Venous Thromboembolism and the Risk of Death and Graft Loss in Kidney Transplant
      Recipients.
AB  - BACKGROUND: The implications of venous thromboembolism (VTE) for morbidity and
      mortality in kidney transplant recipients are not well described. METHODS: We
      conducted a retrospective study using linked healthcare databases in Ontario,
      Canada to determine the risk and complications of VTE in kidney transplant
      recipients from 2003 to 2013. We compared the incidence rate of VTE in recipients
      (n = 4,343) and a matched (1:4) sample of the general population (n = 17,372).
      For recipients with evidence of a VTE posttransplant, we compared adverse
      clinical outcomes (death, graft loss) to matched (1:2) recipients without
      evidence of a VTE posttransplant. RESULTS: During a median follow-up of 5.2
      years, 388 (8.9%) recipients developed a VTE compared to 254 (1.5%) in the
      matched general population (16.3 vs. 2.4 events per 1,000 person-years; hazard
      ratio [HR] 7.1, 95% CI 6.0-8.4; p < 0.0001). Recipients who experienced a
      posttransplant VTE had a higher risk of death (28.5 vs. 11.2%; HR 4.1, 95% CI 2.9
      5.8; p < 0.0001) and death-censored graft loss (13.1 vs. 7.5%; HR 2.3, 95% CI 1.4
      3.6; p = 0.0006) compared to matched recipients who did not experience a
      posttransplant VTE. CONCLUSIONS: Kidney transplant recipients have a sevenfold
      higher risk of VTE compared to the general population with VTE conferring an
      increased risk of death and graft loss.

PMID- 29024936
TI  - Glucose insult elicits hyperactivation of cancer stem cells through miR-424-cdc42
      prdm14 signalling axis.
AB  - BACKGROUND: Meta-analysis shows that women with diabetes have a 20% increased
      risk of breast cancer and also an increased risk for distant metastasis and
      mortality. The molecular mechanisms for distant metastasis and mortality in
      breast cancer patients with diabetes are not very well understood. METHODS: We
      compared the effect of physiological (5 mM) and diabetic (10 mM) levels of
      glucose on malignant breast epithelial cell invasion and stemness capabilities.
      We performed microRNA array to determine the dysregulated microRNAs in
      hyperglycaemic conditions and performed functional and molecular analysis of the
      gene targets. RESULTS: Hyperglycaemia leads to hyperactivation of cancer stem
      cell pool and enhances invasive ability of breast cancer cells. MiR-424 seems to
      be a key regulator of cancer cell stemness and invasion. Knockdown of miR-424 in
      cancer cells under euglycaemic conditions leads to enhanced invasion and stem
      cell activity, whereas ectopic expression of miR-424 in cancer cells under
      hyperglycaemic conditions results in suppressed invasion and stem cell activity.
      Cdc42, a target of miR-424, influences cancer stem cell activity by positively
      regulating prdm14 through activation of pak1 (p-21-activated kinase 1) and stat5.
      CONCLUSIONS: Our findings establish miR-424->?cdc42->?prdm14 axis as a key
      molecular signalling cascade that might influence breast cancer progression in
      diabetic patients through hyperactivation of cancer stem cells.

PMID- 29024937
TI  - Protein biomarkers predictive for response to anti-EGFR treatment in RAS wild
      type metastatic colorectal carcinoma.
AB  - BACKGROUND: Metastatic colorectal cancer (mCRC) patients with mutant KRAS or NRAS
      are ineligible for anti-epidermal growth factor receptor (anti-EGFR) therapy, as
      RAS mutations activate downstream pathways independently of EGFR and induce
      primary resistance. However, even among RAS wild-type (WT) patients, only a
      fraction responds to anti-EGFR therapy, suggesting that other mechanisms of
      resistance exist. We hypothesise that different (epi)genetic alterations can lead
      to primary anti-EGFR resistance and that the crucial end point is the activation
      of protein signalling pathways. METHODS: We analysed the expression and
      activation of proteins involved in cell signalling, using reverse phase protein
      arrays, on a multicentre French cohort of RAS WT mCRC treated with anti-EGFR
      treatment. RESULTS: We identify activated EGFR and HER3 as protein biomarkers
      predictive for better overall survival. Active EGFR signalling and downstream
      PI3K, but not MAPK, pathway activation are associated with response to anti-EGFR
      treatment. Left-sided mCRC displays active ErbB2/3 and Wnt pathways and a better
      response to anti-EGFR therapy compared to right-sided mCRC. CONCLUSIONS: We
      identify active EGFR and PI3K signalling as a key factor for response to anti
      EGFR treatment in mCRC and highlight the importance of developing these
      biomarkers in clinical practice for the selection of RAS WT mCRC patients that
      would benefit from anti-EGFR treatment.

PMID- 29024939
TI  - Ailanthone inhibits non-small cell lung cancer cell growth through repressing DNA
      replication via downregulating RPA1.
AB  - BACKGROUND: The identification of bioactive compounds from Chinese medicine plays
      a crucial role in the development of novel reagents against non-small lung cancer
      (NSCLC). METHODS: High throughput screening assay and analyses of cell growth,
      cell cycle, apoptosis, cDNA microarray, BrdU incorporation and gene expression
      were performed. RESULTS: Ailanthone (Aila) suppressed NSCLC cell growth and
      colony formation in vitro and inhibited NSCLC tumour growth in subcutaneously
      xenografted and orthotopic lung tumour models, leading to prolonged survival of
      tumour-bearing mice. Moreover, Aila induced cell cycle arrest in a dose
      independent manner but did not induce apoptosis in all NSCLC cells. Furthermore,
      1222 genes were differentially expressed upon Aila administration, which were
      involved in 21 signal pathways, such as DNA replication. In addition, Aila dose
      dependently decreased BrdU incorporation and downregulated the expression of
      replication protein A1 (RPA1). CONCLUSIONS: Aila inhibited the growth of NSCLC
      cells through the repression of DNA replication via downregulating RPA1, rather
      than through cell cycle arrest and apoptosis. Our findings suggested that Aila
      could be used as a promising therapeutic candidate for NSCLC patients.

PMID- 29024938
TI  - Expression and role of TYRO3 and AXL as potential therapeutical targets in
      leiomyosarcoma.
AB  - BACKGROUND: Leiomyosarcoma (LMS) are 15% of adult sarcomas and remain seldom
      curable in metastatic phase. The TAM receptors and their ligands are
      overexpressed or activated in multiple malignancies, including LMS. METHODS: The
      TAM receptor and ligand expression was evaluated in LMS cell lines and 358
      sarcoma samples by either gene expression or immunohistochemistry. TYRO3 and AXL
      were knocked down. Crizotinib and foretinib were investigated in vitro. RESULTS:
      High expression of TYRO3 and AXL was detected in LMS cell lines. TYRO3 or AXL
      gene knockdown reduced cell proliferation/colony formation. Crizotinib and
      foretinib decreased TYRO3 and AXL phosphorylation, apoptosis, G2/arrest and
      reduced colony formation. Immunohistochemistry performed in 107 sarcomas showed
      higher expression of TYRO3 and GAS6 in LMS vs other sarcomas and nuclear TYRO3
      only in LMS. Microarray gene expression performed in 251 sarcomas revealed
      significantly higher expression of TYRO3 and GAS6 in LMS than other sarcomas.
      Leiomyosarcoma patients with high expression of GAS6 or PROS1 present a
      significantly worse PFS. CONCLUSIONS: Leiomyosarcoma patients, especially those
      whom develop metastasis, express higher levels of TYRO3 and GAS6. Crizotinib and
      foretinib showed effective antitumour activity in LMS through TYRO3 and AXL
      deactivation indicating that clinical trials using TYRO3 and AXL inhibitors are
      warranted in advanced LMS.

PMID- 29024940
TI  - ANO9/TMEM16J promotes tumourigenesis via EGFR and is a novel therapeutic target
      for pancreatic cancer.
AB  - BACKGROUND: Anoctamin (ANO)/transmembrane member 16 (TMEM16) proteins mediate
      diverse physiological and pathophysiological functions including cancer cell
      proliferation. The present study aimed to identify the role of ANOs in pancreatic
      cancer. METHODS: In an initial screen of ANOs, ANO9/TMEM16J was overexpressed in
      pancreatic cancer cells, and its role in the pathogenesis of pancreatic cancer
      was evaluated using an integrated in vitro and in vivo approach. To determine
      clinical relevance of the experimental findings, the prognostic value of ANO9 was
      evaluated in patients with pancreatic cancer. RESULTS: The ANO9 mRNA and protein
      levels were increased in pancreatic cancer-derived cells. Exogenous expression of
      ANO9 in PANC-1 cells significantly increased cell proliferation in cell cultures
      and in mice. In contrast, knockdown of ANO9 in AsPC-1, BxPC-3, and Capan-2 cells
      strongly inhibited cell proliferation. Mechanistic analysis suggested that
      physical association of ANO9 with epidermal growth factor receptor (EGFR)
      underlies ANO9-induced cell proliferation. Knockdown of ANO9 augmented the
      effects of the EGFR inhibitor and the cytotoxic agent on pancreatic cancer cell
      proliferation. In addition, high ANO9 expression is a poor prognostic factor in
      patients with pancreatic cancer. CONCLUSIONS: The ANO9/TMEM16J appears to be a
      clinically useful prognostic marker for pancreatic cancer and a potential
      therapeutic target.

PMID- 29024941
TI  - In-depth proteomic analysis of tissue interstitial fluid for hepatocellular
      carcinoma serum biomarker discovery.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver.
      New serum biomarkers for HCC screening are needed, especially for alpha
      fetoprotein (AFP) negative patients. As a proximal fluid between body fluids and
      intracellular fluid, tissue interstitial fluid (TIF) is a suitable source for
      serum biomarker discovery. METHODS: Sixteen paired TIF samples from HCC tumour
      and adjacent non-tumour tissues were analysed by isobaric tags for relative and
      absolute quantitation (iTRAQ) method. Two proteins were selected for ELISA
      validation in serum samples. RESULTS: Totally, 3629 proteins were identified and
      3357 proteins were quantified in TIF samples. Among them, 232 proteins were
      significantly upregulated in HCC-TIF and 257 proteins down-regulated. Two
      overexpressed extracellular matrix proteins, SPARC and thrombospondin-2 (THBS2)
      were selected for further validation. ELISA result showed that the serum levels
      of SPARC and THBS2 in HCC patients were both significantly higher than those in
      healthy controls. The combination of serum SPARC and THBS2 could distinguish HCC
      (AUC=0.97, sensitivity=86%, specificity=100%) or AFP-negative HCC (AUC=0.95,
      sensitivity=91%, specificity=93%) from healthy controls. And the combination of
      serum SPARC and THBS2 could also distinguish HCC patients from benign liver
      disease patients (AUC=0.93, sensitivity=80%, specificity=94%). In addition, serum
      THBS2 was found to be a novel independent indicator for poor prognosis of HCC.
      CONCLUSIONS: Novel HCC candidate serum markers were found through in-depth
      proteomic analysis of TIF, which demonstrated the successful utility of TIF in
      cancer serum biomarker discovery.

PMID- 29024948
TI  - HDSS Profile: The South East Asia Community Observatory Health and Demographic
      Surveillance System (SEACO HDSS).

PMID- 29024942
TI  - Loss of Myosin Vb in colorectal cancer is a strong prognostic factor for disease
      recurrence.
AB  - BACKGROUND: Selecting the most beneficial treatment regimens for colorectal
      cancer (CRC) patients remains challenging due to a lack of prognostic markers.
      Members of the Myosin family, proteins recognised to have a major role in
      trafficking and polarisation of cells, have recently been reported to be closely
      associated with several types of cancer and might thus serve as potential
      prognostic markers in the context of CRC. METHODS: We used a previously
      established meta-analysis of publicly available gene expression data to analyse
      the expression of different members of the Myosin V family, namely MYO5A, 5B, and
      5C, in CRC. Using laser-microdissected material as well as tissue microarrays
      from paired human CRC samples, we validated both RNA and protein expression of
      Myosin Vb (MYO5B) and its known adapter proteins (RAB8A and RAB25) in an
      independent patient cohort. Finally, we assessed the prognostic value of both
      MYO5B and its adapter-coupled combinatorial gene expression signatures. RESULTS:
      The meta-analysis as well as an independent patient cohort study revealed a
      methylation-independent loss of MYO5B expression in CRC that matched disease
      progression. Although MYO5B mutations were identified in a small number of
      patients, these cannot be solely responsible for the common downregulation
      observed in CRC patients. Significantly, CRC patients with low MYO5B expression
      displayed shorter overall, disease-, and metastasis-free survival, a trend that
      was further reinforced when RAB8A expression was also taken into account.
      CONCLUSIONS: Our data identify MYO5B as a powerful prognostic biomarker in CRC,
      especially in early stages (stages I and II), which might help stratifying
      patients with stage II for adjuvant chemotherapy.

PMID- 29024947
TI  - Human trophoblast-derived hydrogen sulfide stimulates placental artery
      endothelial cell angiogenesis.
AB  - Endogenous hydrogen sulfide (H2S), mainly synthesized by cystathionine beta
      synthase (CBS) and cystathionine gamma-lyase (CTH), has been implicated in
      regulating placental angiogenesis; however, the underlying mechanisms are
      unknown. This study was to test a hypothesis that trophoblasts synthesize H2S to
      promote placental angiogenesis. Human choriocarcinoma-derived BeWo cells
      expressed both CBS and CTH proteins, while the first trimester villous
      trophoblast-originated HTR-8/SVneo cells expressed CTH protein only. The H2S
      producing ability of BeWo cells was significantly inhibited by either inhibitors
      of CBS (carboxymethyl hydroxylamine hemihydrochloride, CHH) or CTH (beta-cyano-L
      alanine, BCA) and that in HTR-8/SVneo cells was inhibited by CHH only. H2S donors
      stimulated cell proliferation, migration, and tube formation in ovine placental
      artery endothelial cells (oFPAECs) as effectively as vascular endothelial growth
      factor. Co-culture with BeWo and HTR-8/SVneo cells stimulated oFPAEC migration,
      which was inhibited by CHH or BCA in BeWo but CHH only in HTR-8/SVneo cells.
      Primary human villous trophoblasts (HVT) were more potent than trophoblast cell
      lines in stimulating oFPAEC migration that was inhibited by CHH and CHH/BCA
      combination in accordance with its H2S synthesizing activity linked to CBS and
      CTH expression patterns. H2S donors activated endothelial nitric oxide synthase
      (NOS3), v-AKT murine thymoma viral oncogene homolog 1 (AKT1), and extracellular
      signal-activated kinase 1/2 (mitogen-activated protein kinase 3/1, MAPK3/1) in
      oFPAECs. H2S donor-induced NOS3 activation was blocked by AKT1 but not MAPK3/1
      inhibition. In keeping with our previous studies showing a crucial role of AKT1,
      MAPK3/1, and NOS3/NO in placental angiogenesis, these data show that trophoblast
      derived endogenous H2S stimulates placental angiogenesis, involving activation of
      AKT1, NOS3/NO, and MAPK3/1.

PMID- 29024949
TI  - Nutritional optimization during neoadjuvant therapy prior to surgical resection
      of esophageal cancer-a narrative review.
AB  - This narrative review aims to evaluate the evidence for the different nutritional
      approaches employed during neoadjuvant therapy in patients with locoregional
      esophageal cancer. Patients with esophageal cancer are often malnourished and
      difficult to optimize nutritionally. While evidence suggests that neoadjuvant
      therapy can offer a survival advantage, associated toxicity can exacerbate poor
      nutritional status. There is currently no accepted standard of care regarding
      optimal nutritional approach. A systematic literature search was undertaken.
      Studies describing the utilization of an additional nutritional intervention in
      patients with esophageal cancer receiving neoadjuvant therapy prior to
      esophagectomy were included. Primary outcome measure was 30-day postoperative
      mortality after esophagectomy. Secondary outcome measures were loss of weight
      during neoadjuvant therapy, completion rate of intended neoadjuvant therapy,
      complications from nutritional intervention, 30-day postoperative morbidity after
      esophagectomy and quality of life during neoadjuvant treatment. Given the
      heterogeneity of retrieved articles results was presented as a narrative review.
      Twenty-five studies were included of which 16 evaluated esophageal stenting, four
      feeding jejunostomy, three gastrostomy, one nasogastric feeding, and one
      comparative study of esophageal stenting to feeding jejunostomy. 30-day
      postoperative mortality was only reported in two of the 26 included studies
      limiting comparison between nutritional strategies. All studies of esophageal
      stents reported improvements in dysphagia with reported weight change ranging
      from -5.4 to +6 kg and one study reported 30-day postoperative mortality after
      esophagectomy (10%). In patients undergoing esophageal stenting for their
      neoadjuvant treatment overall migration rate was 29.9%. Studies of
      laparoscopically inserted jejunostomy were all retrospective reviews that
      demonstrated an increase in weight ranging from 0.4 to 11.8 kg and similarly no
      study reported 30-day postoperative mortality. Only one comparative study was
      included that compared esophageal stents to jejunostomy. This study reported no
      significant difference between the two groups in respect to complication rates
      (stents 22% vs. jejunostomy 4%, P = 0.11) or increase in weight (stents 4.4 kg
      vs. jejunostomy 4.2 kg, P = 0.59). Quality of life was also poorly reported. This
      review demonstrates the uncertainty on the optimal nutritional approach for
      patients with resectable esophageal cancer undergoing neoadjuvant treatment prior
      to esophagectomy. A prospective, multicenter, observational cohort study is
      needed to determine current practice and inform a prospective clinical trial.

PMID- 29024950
TI  - Serious danger signals: Response to: The effect of neonatal vitamin A
      supplementation on morbidity and mortality at 12 months: a randomized trial.

PMID- 29024952
TI  - A novel reporter mouse to monitor in vivo retrotransposition in the germline.

PMID- 29024951
TI  - Bans of WHO Class I Pesticides in Bangladesh-suicide prevention without hampering
      agricultural output.
AB  - Background: Pesticide self-poisoning is a major problem in Bangladesh. Over the
      past 20-years, the Bangladesh government has introduced pesticide legislation and
      banned highly hazardous pesticides (HHPs) from agricultural use. We aimed to
      assess the impacts of pesticide bans on suicide and on agricultural production.
      Methods: We obtained data on unnatural deaths from the Statistics Division of
      Bangladesh Police, and used negative binomial regression to quantify changes in
      pesticide suicides and unnatural deaths following removal of WHO Class I toxicity
      HHPs from agriculture in 2000. We assessed contemporaneous trends in other risk
      factors, pesticide usage and agricultural production in Bangladesh from 1996 to
      2014. Results: Mortality in hospital from pesticide poisoning fell after the 2000
      ban: 15.1% vs 9.5%, relative reduction 37.1% [95% confidence interval (CI) 35.4
      to 38.8%]. The pesticide poisoning suicide rate fell from 6.3/100 000 in 1996 to
      2.2/100 000 in 2014, a 65.1% (52.0 to 76.7%) decline. There was a modest
      simultaneous increase in hanging suicides [20.0% (8.4 to 36.9%) increase] but the
      overall incidence of unnatural deaths fell from 14.0/100 000 to 10.5/100 000
      [25.0% (18.1 to 33.0%) decline]. There were 35 071 (95% CI 25 959 to 45 666)
      fewer pesticide suicides in 2001 to 2014 compared with the number predicted based
      on trends between 1996 to 2000. This reduction in rate of pesticide suicides
      occurred despite increased pesticide use and no change in admissions for
      pesticide poisoning, with no apparent influence on agricultural output.
      Conclusions: Strengthening pesticide regulation and banning WHO Class I toxicity
      HHPs in Bangladesh were associated with major reductions in deaths and hospital
      mortality, without any apparent effect on agricultural output. Our data indicate
      that removing HHPs from agriculture can rapidly reduce suicides without imposing
      substantial agricultural costs.

PMID- 29024953
TI  - RE: Anal cancer: different epidemiological and clinical definitions.

PMID- 29024954
TI  - Physical activity: A primary health quality determinant among community-dwelling
      geriatric women in Taiwan.
AB  - Objective: To investigate the associations between frailty, physical activity and
      depression in community-dwelling geriatric women. Design: A cross-sectional
      research design. Setting: Community geriatric women in Illan County, Taiwan.
      Study participants: Of note 216 participants, 65 years and older with full
      mobility, independent and able to communicate in Mandarin or Taiwanese Hokkien.
      Main Outcome Measures: An average weekly physical activity score International
      Physical Activity Questionnaire-Short Form (IPAQ-SF) and Taiwan Geriatric
      Depression Scale. Classification and regression tree (CART) analysis was used to
      perform decision analysis. Results: The average IPAQ-SF score for the 216
      participants was 9109.52. When an IPAQ-SF score of 4452 or below was obtained by
      participants, 38% of them encountered depression-like syndromes, regardless of
      their frailty status. Diabetes, high risk of metabolic syndrome and lower
      education were the risk factors found to cause depression among participants with
      low physical activity levels. Conclusions: As women have a longer life expectancy
      and experience twice the rates of depression of men particularly after menopause,
      healthcare providers should emphasize exercise and lifestyle changes in order to
      improve the quality of health in geriatric women.

PMID- 29024956
TI  - Lessons learned from piloting mHealth informatics practice curriculum into a
      medical elective.
AB  - Introduction: This case study reports the development and delivery of an mHealth
      elective piloted for first-year undergraduate medical students at Monash
      University (Australia) and the lessons learned by designers. Results: The
      students were not as adept at using mHealth devices as the literature had
      predicted. Expert speakers using mHealth for practice perceptibly engaged
      students. Force-field analysis was a useful basis for devising end-user
      evaluative research tools for practice. Combining small- and large-group
      discussions with eLearning discussions promoted student engagement with new
      concepts and associated jargon. Assessment by mHealth informatics champions
      supported the students' independent learning. Lessons learned: Promotion of
      mHealth curriculum must be transparent and clear. Our elective delivery was
      hampered by a lack of suitable mobile device ownership and limited availability
      of useful, free apps. Technological jargon required clarification. Educators
      require particular mHealth informatics and educational expertise to support
      mHealth pedagogies. This learning helps to prepare medical curriculum designers
      for addressing evolving mHealth practice horizons.

PMID- 29024957
TI  - Cohort Profile: The Hong Kong Osteoporosis Study and the follow-up study.

PMID- 29024955
TI  - Offspring risk of obesity in childhood, adolescence and adulthood in relation to
      gestational diabetes mellitus: a sex-specific association.
AB  - Background: Animal data suggest sexually dimorphic programming of obesity in
      response to altered intrauterine environment, but the longitudinal impact of
      gestational diabetes mellitus (GDM) on sex-specific risk of offspring obesity in
      humans is unclear. Methods: We conducted a prospective analysis of 15 009 US
      individuals (7946 female and 7063 male) from the Growing-Up Today Study, who were
      followed from 1996 (ages 9-14 years) through 2010. Height and weight from
      validated questionnaires were used to derive body mass index (BMI) at different
      ages. Obesity during childhood (< 18 years) and adulthood (>= 18 years) were
      defined using the International Obesity Task Force and the World Health
      Organization criteria. GDM exposure was identified through self-reported
      questionnaires from mothers. Relative risks were estimated using multivariable
      log-binomial regression models with generalized estimating equations accounting
      for clustering within the same family. Results: Male offspring born from
      pregnancies complicated by GDM had higher BMI compared with non-GDM offspring and
      had increased risk of obesity; the adjusted relative risk [RR, 95% confidence
      interval (CI)] was 1.47 (1.11-1.95) for all age groups, 1.59 (1.05-2.41) for late
      childhood, 1.48 (1.06-2.06) for adolescence and 1.39 (1.00-1.94) for early
      adulthood. No significant association between obesity and maternal GDM was
      observed among female participants (RR = 0.97, 95% CI: 0.71-1.33). Conclusions:
      The association of GDM with offspring obesity from late childhood through early
      adulthood may differ by sex; a significant association was observed among male
      but not female offspring.

PMID- 29024958
TI  - A computable pathology report for precision medicine: extending an observables
      ontology unifying SNOMED CT and LOINC.
AB  - Background: The College of American Pathologists (CAP) introduced the first
      cancer synoptic reporting protocols in 1998. However, the objective of a fully
      computable and machine-readable cancer synoptic report remains elusive due to
      insufficient definitional content in Systematized Nomenclature of Medicine -
      Clinical Terms (SNOMED CT) and Logical Observation Identifiers Names and Codes
      (LOINC). To address this terminology gap, investigators at the University of
      Nebraska Medical Center (UNMC) are developing, authoring, and testing a SNOMED CT
      observable ontology to represent the data elements identified by the synoptic
      worksheets of CAP. Methods: Investigators along with collaborators from the US
      National Library of Medicine, CAP, the International Health Terminology Standards
      Development Organization, and the UK Health and Social Care Information Centre
      analyzed and assessed required data elements for colorectal cancer and invasive
      breast cancer synoptic reporting. SNOMED CT concept expressions were developed at
      UNMC in the Nebraska Lexicon(c) SNOMED CT namespace. LOINC codes for each SNOMED
      CT expression were issued by the Regenstrief Institute. SNOMED CT concepts
      represented observation answer value sets. Results: UNMC investigators created a
      total of 194 SNOMED CT observable entity concept definitions to represent
      required data elements for CAP colorectal and breast cancer synoptic worksheets,
      including biomarkers. Concepts were bound to colorectal and invasive breast
      cancer reports in the UNMC pathology system and successfully used to populate a
      UNMC biobank. Discussion: The absence of a robust observables ontology represents
      a barrier to data capture and reuse in clinical areas founded upon observational
      information. Terminology developed in this project establishes the model to
      characterize pathology data for information exchange, public health, and research
      analytics.

PMID- 29024959
TI  - Limb Laterality Recognition Score: A Reliable Clinical Measure Related to Phantom
      Limb Pain.
AB  - Objective: To explore the usefulness of the limb laterality recognition score as
      a clinical measure of phantom limb pain, regarding test-retest reliability and
      association of limb laterality recognition scores with phantom limb pain
      measures. Design: Retrospective cohort. Setting: Community support group.
      Subjects: Eleven adults who averaged 4.8 years since lower limb amputation due to
      vascular pathologies (N = 9), trauma (N = 1), and cancer (N = 1). Methods:
      Subjects self-reported amputated limb pain using the sensation subsection of the
      Prosthetic Evaluation Questionnaire and back and sound limb pain. Using numbered
      iPads that corresponded to the self-reports, subjects played the Recognise Foot
      game to assess limb laterality recognition ability. Subjects identified the
      laterality of 20 foot images, within two seconds each. The software collected
      accuracy and speed scores in basic, vanilla, and context conditions for two
      rounds in random order. Basic showed feet against black backgrounds, vanilla
      showed feet with various monochromatic backgrounds, and context showed feet in
      clothed or environmental contexts. So that greater accuracy in less time meant a
      better score, accuracy scores were divided by completion speed. Intraclass
      correlation coefficient (ICC)3,1 assessed test-retest reliability. Correlations
      between accuracy/speed and phantom limb pain measures were assessed with
      Spearman's rho (categorical) and Pearson coefficients (continuous). Results:
      Accuracy/speed test-retest reliability was strong (ICC = 0.72) and inversely
      associated with phantom limb pain frequency (context rho = 0.72). Conclusions:
      Limb laterality recognition accuracy/speed in the context condition had good test
      retest reliability and correlated strongly with phantom limb pain frequency.
      Accuracy/speed limb laterality recognition ability relates to phantom limb pain
      and may be a valid clinical or research measure.

PMID- 29024960
TI  - How to identify potentially preventable readmissions by classifying them using a
      national administrative database.
AB  - Importance: Hospital readmissions are being used increasingly as an indicator of
      quality of care. However, it remains difficult to identify potentially
      preventable readmissions. Objectives: To evaluate the identification of
      potentially preventable hospital readmissions by using a classification of
      readmissions based on administrative data. Design and setting: We classified a
      random sample of 455 readmissions to a Dutch university hospital in 2014 using
      administrative data. We compared these results to a classification based on
      reviewing the medical records of these readmissions to evaluate the accuracy of
      classification by administrative data. Main outcome measures: Frequencies of
      categories of readmissions based on reviewing records versus those based on
      administrative data. Cohen's kappa for the agreement between both methods. The
      sensitivity and specificity of the identification of potentially preventable
      readmissions with classification by administrative data. Results: Reviewing the
      medical records of acute readmissions resulted in 28.5% of the records being
      classified as potentially preventable. With administrative data this was 44.1%.
      There was slight agreement between both methods: k 0.08 (95% CI: 0.02-0.15, P <
      0.05). The sensitivity of the classification of potentially preventable
      readmissions by administrative data was 63.1% and the specificity was 63.5%.
      Conclusions: This explorative study demonstrated differences between categorizing
      readmissions based on reviewing records compared to using administrative data.
      Therefore, this tool can only be used in practice with great caution. It is not
      suitable for penalizing hospitals based on their number of potentially
      preventable readmissions. However, hospitals might use this classification as a
      screening tool to identify potentially preventable readmissions more efficiently.

PMID- 29024961
TI  - Epidural Fat and Its Association with Pain, Physical Function, and Disability
      Among Older Adults with Low Back Pain and Controls.
AB  - Objective: To examine epidural fat and its relationship to pain, physical
      function, and disability among older adults with chronic low back pain, chronic
      low back pain plus leg pain, and controls. Design: Cross-sectional, comparative
      study. Setting: Standardized examinations were conducted in a research
      laboratory, and magnetic resonance images were obtained. Subjects: A total of 93
      adults age 60 to 85 years (24 with chronic back pain, 25 with chronic back pain
      plus leg pain, and 44 controls). Methods: Reliability for assessment of epidural
      fat diameter, averaged across spinal levels, was established (intraclass
      correlation coefficient = 0.95). Linear regression was used to explore how
      epidural fat diameter related to self-reported (Short Form-36 Health Survey:
      physical component summary score) and performance-based (stair climb performance)
      measures of physical function among adults with chronic back pain with and
      without leg pain, as compared with controls, while controlling for age, sex, and
      body mass index. Associations between epidural fat and pain intensity and low
      back pain-related disability were also explored (P <= 0.050). Results: Epidural
      fat helped explain self-reported function (P < 0.001); adults with axial low back
      pain (LBP) may have a relationship between epidural fat and self-report function
      that is different from controls (P = 0.015). Relationships between epidural fat
      and stair performance were significantly different from controls for those with
      LBP (P = 0.000) but not for those with LBP plus leg pain (P = 0.366).
      Relationships between epidural fat and pain intensity and/or disability were not
      found. Conclusions: Increased epidural fat may help explain better function among
      older adults with chronic axial back pain, but not among those who also report
      leg pain.

PMID- 29024962
TI  - Age-Related Changes in Headache Days across the Cognitive Spectrum.
AB  - Introduction: Prior studies demonstrating age-related declines in headache
      prevalence have not accounted for the potentially confounding effects of
      cognitive impairment. Our primary goal was to assess the relationship between
      aging and self-reported monthly headache days across the cognitive spectrum.
      Methods: A detailed headache questionnaire was included prospectively as part of
      an annual mailing to participants in the Sanders-Brown Center on Aging
      longitudinal cohort. Results: The overall survey response rate was 58.6%,
      yielding a cohort of 332 cognitively normal, 71 mild cognitive impairment (median
      Mini-Mental Status Examination [MMSE] score = 27, interquartile range [IQR] = 25
      28), and 51 demented (median MMSE score = 24, IQR = 19-26) individuals. Current
      headaches were reported by 22.8%, 25%, and 27.1%, respectively, across normal,
      mild cognitive impairment, and dementia subgroups. A negative correlation was
      observed between age and average headache days in cognitively normal (rho = 
      0.163, 95% confidence interval [CI] = -0.246 to -0.022, P = 0.004), mild
      cognitive impairment (rho = -0.255, 95% CI = -0.274 to 0.229, P = 0.0475), and
      dementia groups (rho = -0.295, 95% CI = -0.457 to 0.159, P = 0.068). Ordinary
      least-squares regression with backward selection identified age alone, but not
      gender or MMSE, as predicting headache days in the overall cohort. Conclusions:
      Aging is associated with a decline in headache days in the absence of any
      confounding cognitive pathology and is weakly predictive of headache days across
      the cognitive spectrum. Whether this represents a reporting bias due to dementia
      or has neurobiological significance warrants further investigation.

PMID- 29024963
TI  - Blue sclera secondary to severe iron deficiency anemia.

PMID- 29024965
TI  - Use of POCUS Ultrasound in sepsis, bedside diagnosis of necrotizing fasciitis.

PMID- 29024964
TI  - A single unit transfusion policy reduces red cell transfusions in general medical
      in-patients.
AB  - Background: The NICE guidelines for blood transfusion and the patient blood
      management recommendations state that a single unit of red cells should be the
      standard dose for patients with stable anaemia who are not bleeding. Studies have
      shown that changing clinical transfusion practice can be difficult and that many
      clinicians' order two units of blood as standard for patients needing a
      transfusion. Aim: A collaborative project between NHS Blood and Transplant and
      Kings College Hospital started in September 2014 to evaluate the impact of a
      single unit policy on blood usage. Design Methods: Training and education was
      undertaken for clinical staff on eight general medical wards and all staff
      working in the blood transfusion laboratory. We collected transfusion data for 12
      months, (6 months before and after implementation). Results: There was a decrease
      of 50% red cell unit usage between the two periods, equating to a unit cost
      saving of L28 670. The number of single unit transfusions, increased from 30 to
      53% whilst the number of two units decreased from 65 to 43% (P < 0.001).
      Discussion/Conclusion: This project has shown that transfusion practice can be
      changed and savings in blood usage can be achieved through the successful
      implementation of the single unit transfusions policy. Key to the implementation
      was engagement from key medical staff within the medical department in which the
      policy was implemented and support from the hospital transfusion team. Continued
      attention and training shall be needed to support these, and implement other,
      patient blood management recommendations.

PMID- 29024967
TI  - Atypical macrophages in disseminated Mycobacterium intracellulare infection.

PMID- 29024966
TI  - Premature coronary artery disease and early stage chronic kidney disease.
AB  - A 30 year old asymptomatic male with stage 3 chronic kidney disease (CKD)
      secondary to Focal Segmental Glomerulosclerosis was found to have features of CKD
      associated cardiomyopathy including left ventricular hypertrophy (LVH) and focal
      sub-endocardial scarring on cardiac magnetic resonance imaging. There was also a
      significantly raised CT coronary calcium score and evidence of non-flow limiting
      coronary artery disease (CAD) on a CT coronary angiogram. Early stage CKD is a
      major risk factor for cardiovascular risk causing myocardial hypertrophy and
      fibrosis and coronary artery atheroma. Cardiovascular risk begins to increase
      from an eGFR of around 75ml/min/1.73m2. The pathophysiology of cardiovascular
      disease in CKD is under investigation but to date, treatment options are limited.
      Blood pressure control and statins have the strongest supportive evidence.

PMID- 29024968
TI  - Iron suppresses ovarian granulosa cell proliferation and arrests cell cycle
      through regulating p38 mitogen-activated protein kinase/p53/p21 pathway.
AB  - Iron is an essential nutrient that may exert toxic effects when it accumulates in
      tissues. Little is known regarding its effects on gonadal function. Both Fe2+ and
      Fe3+ could be released from iron deposition. We employed mouse nonluteinized
      granulosa cell for in vitro studies and human ovarian tissues for Prussian blue
      and immunohistochemical staining to identify the iron deposition and effect in
      vivo. After treatment with FeSO4-7H2O or FeCl3 in granulosa cell cultured with
      follicle-stimulating hormone (FSH) for 48 h, we found that Fe2+ significantly
      suppressed FSH-induced granulosa cell proliferation and arrested the cell cycle
      at the G2/M phase by cell proliferation assay and flow cytometry. Fe2+
      significantly increased intracellular reactive oxygen species (ROS) and ferritin
      levels of mouse granulosa cells. The increases in p21 and p53 messenger RNA and
      protein expression facilitated by Fe2+ treatment in mouse granulosa cells were
      significantly suppressed by separate treatments with p53 small interfering RNA
      and p38 mitogen-activated protein kinase (MAPK) inhibitors. An ROS inhibitor
      downregulated Fe2+-induced increases in p38MAPK expression in mouse granulosa
      cells. Quantitative analysis of immunohistochemical staining revealed that human
      ovarian tissue sections with positive Prussian blue staining had lower levels of
      proliferating cell nuclear antigen expression, but higher levels of p21, p53, and
      CDC25C expression than those with negative Prussian blue staining. Conclusively,
      Fe2+ could directly arrest the cell cycle and inhibit granulosa cell
      proliferation by regulating the ROS-mediated p38MAPK/p53/p21 pathway. Therefore,
      iron can directly affect female gonadal function.

PMID- 29024970
TI  - Microfluidics-based digital quantitative PCR for single-cell small RNA
      quantification.
AB  - Quantitative analyses of small RNAs at the single-cell level have been
      challenging because of limited sensitivity and specificity of conventional real
      time quantitative PCR methods. A digital quantitative PCR (dqPCR) method for
      miRNA quantification has been developed, but it requires the use of proprietary
      stem-loop primers and only applies to miRNA quantification. Here, we report a
      microfluidics-based dqPCR (mdqPCR) method, which takes advantage of the Fluidigm
      BioMark HD system for both template partition and the subsequent high-throughput
      dqPCR. Our mdqPCR method demonstrated excellent sensitivity and reproducibility
      suitable for quantitative analyses of not only miRNAs but also all other small
      RNA species at the single-cell level. Using this method, we discovered that each
      sperm has a unique miRNA profile.

PMID- 29024969
TI  - Preconception urinary phthalate concentrations and sperm DNA methylation profiles
      among men undergoing IVF treatment: a cross-sectional study.
AB  - STUDY QUESTION: Are preconception phthalate and phthalate replacements associated
      with sperm differentially methylated regions (DMRs) among men undergoing IVF?
      SUMMARY ANSWER: Ten phthalate metabolites were associated with 131 sperm DMRs
      that were enriched in genes related to growth and development, cell movement and
      cytoskeleton structure. WHAT IS KNOWN ALREADY: Several phthalate compounds and
      their metabolites are known endocrine disrupting compounds and are pervasive
      environmental contaminants. Rodent studies report that prenatal phthalate
      exposures induce sperm DMRs, but the influence of preconception phthalate
      exposure on sperm DNA methylation in humans is unknown. STUDY DESIGN, SIZE,
      DURATION: An exploratory cross-sectional study with 48 male participants from the
      Sperm Environmental Epigenetics and Development Study (SEEDS).
      PARTICIPANTS/MATERIALS, SETTING, METHODS: The first 48 couples provided a spot
      urine sample on the same day as semen sample procurement. Sperm DNA methylation
      was assessed with the HumanMethylation 450 K array. Seventeen urinary phthalate
      and 1,2-Cyclohexane dicarboxylic acid diisononyl ester (DINCH) metabolite
      concentrations were measured from spot urine samples. The A-clust algorithm was
      employed to identify co-regulated regions. DMRs associated with urinary
      metabolite concentrations were identified via linear models, corrected for false
      discovery rate (FDR). MAIN RESULTS AND ROLE OF CHANCE: Adjusting for age, BMI,
      and current smoking, 131 DMRs were associated with at least one urinary
      metabolite. Most sperm DMRs were associated with anti-androgenic metabolites,
      including mono(2-ethylhexyl) phthalate (MEHP, n = 83), mono(2-ethyl-5-oxohexyl)
      phthalate (MEOHP, n = 16), mono-n-butyl phthalate (MBP, n = 22) and cyclohexane
      1,2-dicarboxylic acid-monocarboxy isooctyl (MCOCH, n = 7). The DMRs were enriched
      in lincRNAs as well as in regions near coding regions. Functional analyses of
      DMRs revealed enrichment of genes related to growth and development as well as
      cellular function and maintenance. Finally, 13% of sperm DMRs were inversely
      associated with high quality blastocyst-stage embryos after IVF. LIMITATIONS,
      REASONS FOR CAUTION: Our modest sample size only included 48 males and additional
      larger studies are necessary to confirm our observed results. Non-differential
      misclassification of exposure is also a concern given the single spot urine
      collection. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge, this is the
      first study to report that preconception urinary phthalate metabolite
      concentrations are associated with sperm DNA methylation in humans. These results
      suggest that paternal adult environmental conditions may influence epigenetic
      reprogramming during spermatogenesis, and in turn, influence early-life
      development. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by
      grant K22-ES023085 from the National Institute of Environmental Health Sciences.
      The authors declare no competing interests.

PMID- 29024971
TI  - Early predictors of Guillain-Barre syndrome in the life course of women.
AB  - Background: We sought to determine if immune disorders early in life were
      associated with the later risk of Guillain-Barre syndrome, a neurological
      disorder thought to be infection-related. Methods: We conducted a longitudinal
      cohort study with 16 108 819 person-years of follow-up for a population of 1 108
      541 parous women in Quebec, Canada (1989-2014). The outcome was Guillain-Barre
      syndrome. We identified women with potential risk factors for future Guillain
      Barre syndrome, including immune-mediated and rheumatological diseases, cancer,
      transfusion, surgical procedures and pregnancy-specific disorders. We estimated
      hazard ratios (HR) and 95% confidence intervals (CI) for the association of risk
      factors with later onset of Guillain-Barre syndrome, adjusted for personal
      characteristics of women. Results: The overall incidence of Guillain-Barre
      syndrome was 1.42 per 100 000 person-years. Incidence was higher for women with
      immune-mediated (8.79 per 100 000 person-years) and rheumatological disorders
      (9.84 per 100 000 person-years), transfusion (4.41 per 100 000 person-years), and
      preeclampsia (2.62 per 100 000 person-years). Immune-mediated disorders were
      associated with six times the risk of Guillain-Barre syndrome (HR 6.57, 95% CI
      3.58 to 12.04), rheumatological disorders with seven times the risk (HR 7.23, 95%
      CI 3.21 to 16.28), transfusion three times the risk (HR 3.58, 95% CI 1.83 to
      6.98) and preeclampsia two times the risk (HR 2.01, 95% CI 1.29 to 3.12). Women
      with other potential risk factors did not have an increased risk of Guillain
      Barre syndrome. Conclusions: Immune-related conditions that occur early in life
      are associated with an increased risk of Guillain-Barre syndrome. The
      pathophysiology of Guillain-Barre syndrome may extend beyond infectious triggers.

PMID- 29024972
TI  - Effect of metabolic status on conceptus-maternal interactions on day 19 in dairy
      cattle: II. Effects on the endometrial transcriptome.
AB  - The aim of this study was to test the hypothesis that the metabolic stresses
      associated with lactation alter the ability of the endometrium to respond
      appropriately to the conceptus by examining endometrial gene expression on day 19
      of pregnancy. Immediately after calving, primiparous Holstein cows with similar
      production and fertility estimated breeding values were randomly divided into two
      groups and either dried off (i.e. never milked) immediately or milked twice
      daily. Approximately 65-75 days postpartum, grade 1 blastocysts recovered from
      superovulated Holstein heifer donors (n = 5) were transferred (1 per recipient)
      into lactating (n = 11) and nonlactating (n = 11) recipients. Control nulliparous
      Holstein heifers (n = 6) were artificially inseminated. RNA-sequencing was
      performed on intercaruncular endometrial samples recovered at slaughter from
      confirmed pregnant animals on day 19 (n = 5 lactating and nonlactating cows; n =
      4 heifers). Differentially expressed genes (DEGs) were identified between both
      postpartum groups compared to heifers and between lactating and nonlactating
      cows. Functional annotation of DEGs between cows and heifers revealed over
      representation of categories, including endosome, cytoplasmic vesicle,
      endocytosis, regulation of exocytosis, and cytokine receptor activity. Functional
      categories including transcription factor binding sites, cell motility, and cell
      migration were enriched for DEGs between endometria from lactating and
      nonlactating cows. In conclusion, while the evidence for a major effect of
      lactation on the endometrial transcriptome is relatively weak, these data suggest
      that the metabolic status of the animal (heifer vs cow) modulates the response of
      the endometrium to the developing conceptus.

PMID- 29024973
TI  - Re-employment, job quality, health and allostatic load biomarkers: prospective
      evidence from the UK Household Longitudinal Study.
AB  - Background: There is little evidence on whether becoming re-employed in poor
      quality work is better for health and well-being than remaining unemployed. We
      examined associations of job transition with health and chronic stress-related
      biomarkers among a population-representative cohort of unemployed British adults.
      Methods: A prospective cohort of 1116 eligible participants aged 35 to 75 years,
      who were unemployed at wave 1 (2009/10) of the UK Household Longitudinal Study,
      were followed up at waves 2 (2010/11) and 3 (2011/12) for allostatic load
      biomarkers and self-reported health. Negative binomial and multiple regression
      models estimated the association between job adversity and these outcomes.
      Results: Compared with adults who remained unemployed, formerly unemployed adults
      who transitioned into poor quality jobs had higher levels of overall allostatic
      load (0.51, 0.32-0.71), log HbA1c (0.06, <0.001-0.12), log triglycerides (0.39,
      0.22-0.56), log C-reactive protein (0.45, 0.16-0.75), log fibrinogen (0.09, 0.01
      0.17) and total cholesterol to high-density lipoprotein (HDL) ratio (1.38, 0.88
      1.88). Moreover, physically healthier respondents at wave 1 were more likely to
      transition into good quality and poor quality jobs after 1 year than those who
      remained unemployed. Conclusions: Formerly unemployed adults who transitioned
      into poor quality work had greater adverse levels of biomarkers compared with
      their peers who remained unemployed. The selection of healthier unemployed adults
      into these poor quality or stressful jobs was unlikely to explain their elevated
      levels of chronic stress-related biomarkers. Job quality cannot be disregarded
      from the employment success of the unemployed, and may have important
      implications for their health and well-being.

PMID- 29024976
TI  - A conceptual framework for evaluating data suitability for observational studies.
AB  - Objective: To contribute a conceptual framework for evaluating data suitability
      to satisfy the research needs of observational studies. Materials and Methods:
      Suitability considerations were derived from a systematic literature review on
      researchers' common data needs in observational studies and a scoping review on
      frequent clinical database design considerations, and were harmonized to
      construct a suitability conceptual framework using a bottom-up approach. The
      relationships among the suitability categories are explored from the perspective
      of 4 facets of data: intrinsic, contextual, representational, and accessible. A
      web-based national survey of domain experts was conducted to validate the
      framework. Results: Data suitability for observational studies hinges on the
      following key categories: Explicitness of Policy and Data Governance, Relevance,
      Availability of Descriptive Metadata and Provenance Documentation, Usability, and
      Quality. We describe 16 measures and 33 sub-measures. The survey uncovered the
      relevance of all categories, with a 5-point Likert importance score of 3.9 +/-
      1.0 for Explicitness of Policy and Data Governance, 4.1 +/- 1.0 for Relevance,
      3.9 +/- 0.9 for Availability of Descriptive Metadata and Provenance
      Documentation, 4.2 +/- 1.0 for Usability, and 4.0 +/- 0.9 for Quality.
      Conclusions: The suitability framework evaluates a clinical data source's fitness
      for research use. Its construction reflects both researchers' points of view and
      data custodians' design features. The feedback from domain experts rated
      Usability, Relevance, and Quality categories as the most important
      considerations.

PMID- 29024975
TI  - Comparing methods to address bias in observational data: statin use and
      cardiovascular events in a US cohort.
AB  - Background: The theoretical conditions under which causal estimates can be
      derived from observational data are challenging to achieve in the real world.
      Applied examples can help elucidate the practical limitations of methods to
      estimate randomized-controlled trial effects from observational data. Methods: We
      used six methods with varying design and analytic features to compare the 5-year
      risk of incident myocardial infarction among statin users and non-users, and used
      non-cardiovascular mortality as a negative control outcome. Design features
      included restriction to a statin-eligible population and new users only; analytic
      features included multivariable adjustment and propensity score matching.
      Results: We used data from 5294 participants in the Cardiovascular Health Study
      from 1989 to 2004. For non-cardiovascular mortality, most methods produced
      protective estimates with confidence intervals that crossed the null. The hazard
      ratio (HR) was 0.92, 95% confidence interval: 0.58, 1.46 using propensity score
      matching among eligible new users. For myocardial infarction, all estimates were
      strongly protective; the propensity score-matched analysis among eligible new
      users resulted in a HR of 0.55 (0.29, 1.05)-a much stronger association than
      observed in randomized controlled trials. Conclusions: In designs that compare
      active treatment with non-treated participants to evaluate effectiveness, methods
      to address bias in observational data may be limited in real-world settings by
      residual bias.

PMID- 29024977
TI  - Safer paediatric surgical teams: A 5-year evaluation of crew resource management
      implementation and outcomes.
AB  - Objective: Evaluate longitudinal changes in technical and non-technical skills
      (teamwork, situation monitoring, communication and leadership), safety culture,
      and clinical outcomes before and after implementation of a crew resource
      management (CRM) safety program. Design: A multi-level prospective single case
      study in accordance with the SQUIRE-guidelines for reporting quality improvement
      efforts. Setting: Large university paediatric surgical service. Participant(s):
      All 153 managers and staff. Interventions: Training of staff in CRM, systematic
      risk assessments, and the redesign of work practices captured and reinforced
      through the development, implementation and refinement of SOPs. Main Outcome
      Measure(s): Data were collected related to: 1) Relevance of CRM training
      (survey), 2) Safety culture (survey), 3) Team behaviours in clinical practice
      (non-participatory observations with MedPACT protocol) and 4) Effects on
      perioperative care for laparoscopic appendectomies-a representative and
      frequently performed surgical procedure (electronic medical records and
      administrative data for length of stay, unplanned readmissions and returns to the
      Operating Room). Results: Non-technical skills, the use of safety tools, as well
      as adherence to guidelines for appendectomies all improved significantly over
      time. Significant safety culture improvements were found in teamwork across and
      within units, supervisors' expectations and actions, non-punitive response to
      adverse events, and perceptions of overall patient safety. Unplanned readmissions
      following appendectomy declined significantly. Conclusions: Implementation of a
      comprehensive CRM program including associated safety tools created sustained
      adherence to new work practices and improved non-technical and technical skills,
      surgical outcomes and safety culture.

PMID- 29024974
TI  - Functional Recovery in Major Depressive Disorder: Providing Early Optimal
      Treatment for the Individual Patient.
AB  - Major depressive disorder is an often chronic and recurring illness. Left
      untreated, major depressive disorder may result in progressive alterations in
      brain morphometry and circuit function. Recent findings, however, suggest that
      pharmacotherapy may halt and possibly reverse those effects. These findings,
      together with evidence that a delay in treatment is associated with poorer
      clinical outcomes, underscore the urgency of rapidly treating depression to full
      recovery. Early optimized treatment, using measurement-based care and customizing
      treatment to the individual patient, may afford the best possible outcomes for
      each patient. The aim of this article is to present recommendations for using a
      patient-centered approach to rapidly provide optimal pharmacological treatment to
      patients with major depressive disorder. Offering major depressive disorder
      treatment determined by individual patient characteristics (e.g., predominant
      symptoms, medical history, comorbidities), patient preferences and expectations,
      and, critically, their own definition of wellness provides the best opportunity
      for full functional recovery.

PMID- 29024979
TI  - Are Opioids Really Safe in Patients with Congestive Heart Failure?

PMID- 29024978
TI  - Incidence rate estimation, periodic testing and the limitations of the mid-point
      imputation approach.
AB  - Background: It is common to use the mid-point between the latest-negative and
      earliest-positive test dates as the date of the infection event. However, the
      accuracy of the mid-point method has yet to be systematically quantified for
      incidence studies once participants start to miss their scheduled test dates.
      Methods: We used a simulation-based approach to generate an infectious disease
      epidemic for an incidence cohort with a high (80-100%), moderate (60-79.9%), low
      (40-59.9%) and poor (30-39.9%) testing rate. Next, we imputed a mid-point and
      random-point value between the participant's latest-negative and earliest
      positive test dates. We then compared the incidence rate derived from these
      imputed values with the true incidence rate generated from the simulation model.
      Results: The mid-point incidence rate estimates erroneously declined towards the
      end of the observation period once the testing rate dropped below 80%. This
      decline was in error of approximately 9%, 27% and 41% for a moderate, low and
      poor testing rate, respectively. The random-point method did not introduce any
      systematic bias in the incidence rate estimate, even for testing rates as low as
      30%. Conclusions: The mid-point assumption of the infection date is unjustified
      and should not be used to calculate the incidence rate once participants start to
      miss the scheduled test dates. Under these conditions, we show an artefactual
      decline in the incidence rate towards the end of the observation period.
      Alternatively, the single random-point method is straightforward to implement and
      produces estimates very close to the true incidence rate.

PMID- 29024980
TI  - Comorbid Pain Syndromes in HIV-Associated Peripheral Neuropathy.
AB  - Objective: Peripheral neuropathy (PN) is a common complication of HIV. There is
      increasing awareness that some forms of PN, particularly small-fiber
      neuropathies, can be associated with chronic widespread pain syndromes. Given the
      high prevalence of both PN and chronic pain in HIV, we sought to determine
      whether patients with a diagnosis of HIV-PN were more likely to experience other
      chronic pain syndromes. Methods: Data were obtained from the Clinical Data
      Warehouse maintained by our institution. All HIV-infected patients receiving
      standard of care antiretroviral therapy in our institution's primary care HIV
      clinic (N = 638) were included. Diagnoses of HIV-PN and other chronic pain
      disorders were established based on clinician-assigned ICD-9/10 codes. Results:
      Sixty-eight patients (11%) had a diagnosis of HIV-PN. Patients with HIV-PN were
      more than twice as likely to have other chronic pain disorders (66% vs 32%, chi2
      = 30.3, P < 0.001). Patients with HIV-PN were also older and more likely to have
      substance use and psychiatric disorders; however, the association of HIV-PN with
      other chronic pain disorders persisted after adjusting for relevant confounders
      (chi2(5) = 81.38, P < 0.001). Conclusions: Patients with HIV-PN commonly
      experience other chronic pain disorders. Clinicians managing HIV-PN should seek a
      broad understanding of patients' pain experience as this may alter management
      strategies. Researchers studying HIV-PN should consider how the presence of other
      pain disorders might affect outcomes.

PMID- 29024981
TI  - Diabetes in pregnancy: worse medical outcomes in type 1 diabetes but worse
      psychological outcomes in gestational diabetes.
AB  - Background: Women with diabetes experience an increased risk of adverse pregnancy
      outcomes. Aim: We aim to describe and quantify the psychological impact of the
      diagnosis of diabetes in pregnant women with type 1 diabetes and gestational
      diabetes mellitus (GDM) compared to each other and to their counterparts without
      diabetes. Design: This is a survey-based study with prospective collection of
      pregnancy outcome data. Methods: A total of 218 pregnant women (50% with
      diabetes) were administered questionnaires relating to psychological health.
      Maternal and neonatal characteristics and pregnancy outcomes were collected.
      Associations between key psychometric and health outcome variables were examined.
      Results: At least 25% of women in all three pregnancy groups had scores
      indicating affective distress in at least one domain. Compared to those with type
      1 diabetes, women with GDM evidenced a greater number of uplifts in pregnancy (U
      = 94, P = 0.041), but also higher levels of overall anxiety (U = 92, P = 0.03)
      and stress (U = 82, P < 0.01). Women with GDM also had significantly elevated
      overall depression scores, compared with the control group (U = 34, P = 0.02).
      Both groups of women with diabetes had clinically elevated levels of diabetes
      related distress. There were no associations between maternal psychological
      variables and pregnancy outcomes. Conclusions: This work highlights a potential
      role for targeted psychological interventions to address and relieve symptoms of
      anxiety and depression among pregnant women with diabetes.

PMID- 29024983
TI  - 24/7 Consultant working in the NHS: 12 years experience in intensive care.

PMID- 29024982
TI  - Re-examining the link between prenatal maternal anxiety and child emotional
      difficulties, using a sibling design.
AB  - Background: Prenatal exposure to maternal anxiety has been associated with child
      emotional difficulties in a number of epidemiological studies. One key concern,
      however, is that this link is vulnerable to confounding by pleiotropic genes or
      environmental family factors. Methods: Data on 82 383 mothers and children from
      the population-based Mother and Child Cohort Study and data on 21 980 siblings
      were used in this study. Mothers filled out questionnaires for each unique
      pregnancy, for infant difficulties at 6 months and for emotional difficulties at
      36 months. The link between prenatal maternal anxiety and child difficulties were
      examined using logistic regression analyses and multiple linear regression
      analyses for the full study sample and the sibling sample. Results: In the
      conventional full-cohort analyses, prenatal exposure to maternal anxiety was
      associated with child difficulties at both 6 months [odds ratio (OR) = 2.1 (1.94
      2.27)] and 36 months [OR = 2.72 (2.47-2.99)]. The findings were essentially the
      same whether we examined difficulties at 6 months or at 36 months. However, these
      associations were no longer present once we controlled for potential social and
      genetic confounders in the sibling comparison analyses, either at 6 months [OR =
      1.32 (0.91-1.90)] or at 36 months [OR = 1.28 (0.63-2.60)]. Findings from multiple
      regression analyses with continuous measures were essentially the same.
      Conclusions: Our finding lends little support for there being an independent
      prenatal effect on child emotional difficulties; rather, our findings suggest
      that the link between prenatal maternal anxiety and child difficulties could be
      confounded by pleiotropic genes or environmental family factors.

PMID- 29024984
TI  - Prevention of and dealing with poor performance: an interview study about how
      professional associations aim to support healthcare professionals.
AB  - Objective: To explore how professional associations of nine healthcare
      professions aim to support professionals to prevent and deal with poor
      performance. Design: Qualitative interview study. Setting: The Netherlands.
      Participants: Representatives of professional associations for dentists, general
      practitioners, medical specialists, midwives, nurses, pharmacists,
      physiotherapists, psychologists and psychotherapists. Interventions: During nine
      face-to-face semi-structured interviews we asked how associations aim to support
      professionals in prevention of and dealing with poor performance. Following the
      first interview, we monitored new initiatives in support over a 2.5-year period,
      after which we conducted a second interview. Interviews were analysed using
      thematic analysis. Main outcome measures: Available policy and support regarding
      poor performance. Results: Three themes emerged from our data (i.e. elaborating
      on professional performance, performance insight and dealing with poor
      performance) for which we identified a total of 10 categories of support. Support
      concerned professional codes, guidelines and codes of conduct, quality registers,
      individual performance assessment, peer consultation, practice evaluation,
      helpdesk and expert counselling, a protocol for dealing with poor performance, a
      place for support and to report poor performance, and internal disciplinary
      procedures. Conclusions: This study provides an overview of support given to nine
      healthcare professions by their associations regarding poor performance, and
      identifies gaps that associations could follow up on, such as clarifying what to
      do when confronted with a poorly performing colleague, supporting professionals
      that poorly perform, and developing methods for individual performance assessment
      to gain performance insight. A next step would be to evaluate the use and effect
      of different types of support.

PMID- 29024985
TI  - Transient global amnesia: clinical and imaging features.

PMID- 29024987
TI  - Development and Validation of an Eight-Item Brief Form of the SOAPP-R (SOAPP-8).
AB  - Objective: Although the Screener and Opioid Assessment for Patients with Pain
      Revised (SOAPP-R) has become a widely used screener for aberrant opioid-related
      behavior in adults, the length of the instrument may limit its utility. The
      purpose of the current study was to develop a short form of the SOAPP-R by
      retaining as few items as possible while maximizing predictive accuracy. Methods:
      Participants (N = 555), recruited from pain clinics, completed the 24-item SOAPP
      R and participated in a five-month follow-up visit to evaluate aberrant drug
      related behaviors. Opioid aberrant-related behavior was determined through self
      report, physician report, and urine toxicology screen. The optimal subset of
      SOAPP-R items to predict aberrant opioid-related behavior was identified
      empirically by employing the LASSO selection method and the leave-one-out cross
      validation (LOOCV) method offered in the GLMSELECT procedure in SAS 9.4 in
      conjunction with content expertise. Results: Eight items were identified before
      the selection method stopped. The receiver operating characteristic curve
      generated from the predicted probabilities from the model produced an area under
      the curve (AUC) value greater than the AUC value produced by the 24-item SOAPP-R
      total score and yielded a sensitivity of 0.74 and a specificity of 0.66.
      Conclusions: These results provide strong preliminary support for the SOAPP-8 as
      a brief screening tool of aberrant opioid-related behavior in chronic pain
      patients.

PMID- 29024986
TI  - Stromal fibroblasts from perimenopausal endometrium exhibit a different
      transcriptome than those from the premenopausal endometrium.
AB  - Human endometrium undergoes extensive regeneration on a cyclic basis in
      premenopausal women and likely occurs through the contribution of stem/progenitor
      cells. Menopause results in the permanent cessation of menstrual cycles and is
      preceded by perimenopause, a period of several years in which endocrine and
      biological changes occur and is a period of risk for endometrial proliferative
      disorders. The objectives of this study were to identify endometrial mesenchymal
      stem cells (eMSC) and endometrial stromal fibroblasts (eSF) in endometrium of
      perimenopausal women and perform expression profile analysis of perimenopausal
      eMSC and eSF to gain insight into the biology of stem/progenitor and lineage cell
      populations during the transition to menopause. Endometrial tissue was collected
      from perimenopausal and premenopausal women (n = 9 each). Microarray analysis was
      performed on fluorescence-activated cell sorting-isolated eSF and eMSC, and data
      were validated by quantitative real-time PCR. Principal component analysis showed
      that cells clustered into three distinct groups in 3-dimensional space:
      perimenopausal eMSC and premenopausal eMSC clustered together, while
      perimenopausal eSF and premenopausal eSF formed two discrete clusters separate
      from eMSC. Hierarchical clustering revealed a branching pattern consistent with
      principle clustering analysis results, indicating that eMSC from premenopausal
      and perimenopausal women exhibit similar transcriptomic signatures. Pathway
      analysis revealed dysregulation of cytoskeleton, proliferation, and survival
      pathways in perimenopausal vs. premenopausal eSF. These data demonstrate that
      cell populations have altered gene expression in perimenopausal vs. premenopausal
      endometrium, and that perimenopausal eSF had altered pathway activation when
      compared to premenopausal eSF. This study provides insight into aging endometrium
      with relevance to function in reproductively older women.

PMID- 29024989
TI  - Suggested Reporting Guidelines to Improve Health-Related Social Work Research.

PMID- 29024988
TI  - Low-dose metronomic delivery of cyclophosphamide is less detrimental to granulosa
      cell viability, ovarian function, and fertility than maximum tolerated dose
      delivery in the mouse.
AB  - Chemotherapy can cause early menopause or infertility in women and have a
      profound negative impact on the quality of life of young female cancer survivors.
      Various factors are known to influence the risk of chemotherapy-induced ovarian
      failure, including the drug dose and treatment duration; however, the scheduling
      of dose administration has not yet been evaluated as an independent risk factor.
      We hypothesized that low-dose metronomic (LDM) chemotherapy scheduling would be
      less detrimental to ovarian function than the traditional maximum tolerated dose
      (MTD) strategy. In vitro, MTD cyclophosphamide exposure resulted in decreased
      proliferation and increased granulosa cell apoptosis, while cells treated with
      LDM cyclophosphamide were not different from untreated controls. Treatments of
      MTD cyclophosphamide induced high levels of follicle atresia and enhanced
      follicle recruitment in mice. In contrast, LDM delivery of an equivalent dose of
      cyclophosphamide reduced growing follicle numbers, but was not associated with
      higher levels of follicle atresia or recruitment. MTD cyclophosphamide induced
      significant vascular disruption and DNA damage in vivo, while LDM chemotherapy
      with equal cumulative amounts of cyclophosphamide was not different from
      controls. MTD chemotherapy also had a negative effect on mouse-fertility
      outcomes. Our findings suggest that LDM scheduling could potentially minimize the
      long-term effects of cyclophosphamide on female fertility by preventing follicle
      depletion from enhanced activation.

PMID- 29024990
TI  - Myocarditis and purpura fulminans in meningococcaemia.

PMID- 29024991
TI  - Association between pre-pregnancy overweight and obesity and children's
      neurocognitive development: a systematic review and meta-analysis of
      observational studies.

PMID- 29024992
TI  - Formation and function of sperm tail structures in association with sperm
      motility defects.
AB  - Male infertility is an increasing problem partly due to inherited genetic
      variations. Mutations in genes involved in formation of the sperm tail cause
      motility defects and thus male infertility. Therefore, it is crucial to
      understand the protein networks required for sperm differentiation. Sperm
      motility is produced through activation of the sperm flagellum, which core
      structure, the axoneme, resembles motile cilia. In addition to this, cytoskeletal
      axonemal structure sperm tail motility requires various accessory structures.
      These structures are important for the integrity of the long tail, sperm
      capacitation, and generation of energy during sperm passage to fertilize the
      oocyte. This review discusses the current knowledge of mechanisms required for
      formation of the sperm tail structures and their effect on fertility. The recent
      research based on animal models and genetic variants in relation to sperm tail
      formation and function provides insights into the events leading to fertile sperm
      production. Here we compile a view of proteins involved in sperm tail development
      and summarize the current knowledge of factors contributing to reduced sperm
      motility, asthenozoospermia, underline the mechanisms which require further
      research, and discuss related clinical aspects on human male infertility.

PMID- 29024993
TI  - Ultrasonographic findings as diagnostic and follow-up tool in cranial giant cell
      arteritis.

PMID- 29024994
TI  - Pancreatic cancer incidence rises also in Italy.

PMID- 29024995
TI  - The equity impact of community women's groups to reduce neonatal mortality: a
      meta-analysis of four cluster randomized trials.
AB  - Background: Socioeconomic inequalities in neonatal mortality are substantial in
      many developing countries. Little is known about how to address this problem.
      Trials in Asia and Africa have shown strong impacts on neonatal mortality of a
      participatory learning and action intervention with women's groups. Whether this
      intervention also reduces mortality inequalities remains unknown. We describe the
      equity impact of this women's groups intervention on the neonatal mortality rate
      (NMR) across socioeconomic strata. Methods: We conducted a meta-analysis of all
      four participatory women's group interventions that were shown to be highly
      effective in cluster randomized trials in India, Nepal, Bangladesh and Malawi. We
      estimated intervention effects on NMR and health behaviours for lower and higher
      socioeconomic strata using random effects logistic regression analysis.
      Differences in effect between strata were tested. Results: Analysis of 69120 live
      births and 2505 neonatal deaths shows that the intervention strongly reduced the
      NMR in lower (50-63% reduction depending on the measure of socioeconomic position
      used) and higher (35-44%) socioeconomic strata. The intervention did not show
      evidence of 'elite-capture': among the most marginalized populations, the NMR in
      intervention areas was 63% lower [95% confidence interval (CI) 48-74%] than in
      control areas, compared with 35% (95% CI: 15-50%) lower among the less
      marginalized in the last trial year ( P -value for difference between most/less
      marginalized: 0.009). The intervention strongly improved home care practices,
      with no systematic socioeconomic differences in effect. Conclusions:
      Participatory women's groups with high population coverage benefit the survival
      chances of newborns from all socioeconomic strata, and perhaps especially those
      born into the most deprived households.

PMID- 29024996
TI  - Encephalitis after influenza and vaccination: a nationwide population-based
      registry study from Norway.
AB  - Background: Influenza is known to be associated with various neurological
      complications, including encephalitis. We conducted a registry-based study to
      assess the risk of encephalitis after influenza and A(H1N1)pdm09 vaccine.
      Methods: Data from Norwegian national health registries during 2008-14 were
      linked using the unique personal identifiers given to all Norwegian residents (N
      = 5 210 519). Cox proportional-hazard models with time-varying variables were
      fitted to estimate hazard ratios (HRs) of encephalitis after influenza and
      A(H1N1)pdm09 vaccine, using the risk windows 0-7, 0-14, 0-30, 0-60, 0-90 and 0
      180 days. Results: In Norway, 684 172 individuals received an influenza diagnosis
      and 2793 patients were hospitalized with encephalitis during 2008-14. The risk of
      encephalitis increased after influenza: HR, 7-day risk window: 47.8 (95%
      confidence interval (CI): 35.8-63.8), and the HR decreased for longer risk
      windows; HR, 180-day risk window: 3.8 (95% CI: 3.1-4.7). HR of encephalitis after
      influenza during the 2009 main pandemic wave using a 7-day risk window was 30.0
      (95% CI: 10.8-83.2). We found no differences in the risk of encephalitis after
      the seasonal influenza compared with influenza during the 2009 main pandemic
      wave; HR, 7-day risk window: 1.3 (95% CI: 0.4-4.3). A(H1N1)pdm09 vaccine was not
      associated with the risk of encephalitis: HR, 14-day risk window: 0.6 (95% CI:
      0.2-2.1). Conclusions: There was an increased risk of encephalitis following
      influenza but not after A(H1N1)pdm09 vaccine. The risk of encephalitis was
      highest in the first few weeks after influenza.

PMID- 29024997
TI  - Evaluation of the effects of the French pay-for-performance program-IFAQ pilot
      study.
AB  - Objective: Most studies showed no or little effect of pay-for-performance (P4P)
      programs on different outcomes. In France, the P4P program IFAQ was generalized
      to all acute care hospitals in 2016. A pilot study was launched in 2012 to
      design, implement and assess this program. This article aims to assess the
      immediate impact of the 2012-14 pilot study. Design and setting: From nine
      process quality indicators (QIs), an aggregated score was constructed as the
      weighted average, taking into account both achievement and improvement. Among 426
      eligible volunteer hospitals, 222 were selected to participate. Eligibility
      depended on documentation of QIs and results of hospital accreditation. Hospitals
      with scores above the median received a financial reward based on their ranking
      and budget. Several characteristics known to have an influence on P4P results
      (patient age, socioeconomic status, hospital activity, casemix and location) were
      used to adjust the models. Intervention: To assess the effect of the program,
      comparison between the 185 eligible selected hospitals and the 192 eligible not
      selected volunteers were done using the difference-in-differences method.
      Results: Whereas all hospitals improved from 2012 to 2014, the difference-in
      differences effect was positive but not significant both in the crude (2.89, P =
      0.29) and adjusted models (4.07, P = 0.12). Conclusion: These results could be
      explained by several reasons: low level of financial incentives, unattainable
      goals, too short study period. However, the lack of impact for the first year
      should not undermine the implementation of other P4P programs. Indeed, the pilot
      study helped to improve the final model used for generalization.

PMID- 29024998
TI  - Response to: 'Serious danger signals', response to: 'The effect of neonatal
      vitamin A supplementation on morbidity and mortality at 12 months: a randomized
      trial'.

PMID- 29024999
TI  - The Great Recession and inequalities in access to health care: a study of
      unemployment and unmet medical need in Europe in the economic crisis.
AB  - Background: Unmet medical need (UMN) had been declining steadily across Europe
      until the 2008 Recession, a period characterized by rising unemployment. We
      examined whether becoming unemployed increased the risk of UMN during the Great
      Recession and whether the extent of out-of-pocket payments (OOP) for health care
      and income replacement for the unemployed (IRU) moderated this relationship.
      Methods: We used the European Survey on Income and Living Conditions (EU-SILC) to
      construct a pseudo-panel (n = 135 529) across 25 countries to estimate the
      relationship between unemployment and UMN. We estimated linear probability
      models, using a baseline of employed people with no UMN, to test whether this
      relationship is mediated by financial hardship and moderated by levels of OOP and
      IRU. Results: Job loss increased the risk of UMN [beta = 0.027, 95% confidence
      interval (CI) 0.022-0.033] and financial hardship exacerbated this effect. Fewer
      people experiencing job loss lost access to health care in countries where OOPs
      were low or in countries where IRU is high. The results are robust to different
      model specifications. Conclusions: Unemployment does not necessarily compromise
      access to health care. Rather, access is jeopardized by diminishing financial
      resources that accompany job loss. Lower OOPs or higher IRU protect against loss
      of access, but they cannot guarantee it. Policy solutions should secure financial
      protection for the unemployed so that resources do not have to be diverted from
      health.

PMID- 29025000
TI  - The Relationship of Auriculotemporal Neuralgia and Epicrania Fugax.

PMID- 29025001
TI  - Using patient-reported outcome measurement to improve patient care.
AB  - Patients at the center of care is often the stated focus of clinicians and
      healthcare services. The quality and safety movement has shown that effective
      organization of care is needed, in addition to professional skills. This movement
      has provided professionals and others with methods to improve both organization
      and practice for patients. These methods include measurement to give those
      carrying out improvement feedback about the effects of their changes. New types
      of measures that enable patients to report treatment outcomes can now be use in
      quality improvement and quality reporting to bring a renewed focus on making care
      more patient-centered. Although used for some time in research, these measures
      are relatively new tools for quality improvement and not all research measures
      are suitable for everyday feedback or improvement projects. The purpose of the
      paper is to provide an introduction to the use and value of patient-reported
      outcome measures in quality improvement and to give practical guidance and
      resources for using PROMs for quality improvement. It draws on the authors'
      experiences using patient reported outcomes measures for quality research and
      improvement and their workshop at the 2016 Tokyo ISQUA conference, as well as on
      reviews and guidance documents about the use of PROMs. It does not provide a
      comprehensive and systematic review of research, but an overview and introduction
      to PROMs for quality improvement.

PMID- 29025002
TI  - Assessing the quality of administrative data for research: a framework from the
      Manitoba Centre for Health Policy.
AB  - The growth of administrative data repositories worldwide has spurred the
      development and application of data quality frameworks to ensure that research
      analyses based on these data can be used to draw meaningful conclusions. However,
      the research literature on administrative data quality is sparse, and there is
      little consensus regarding which dimensions of data quality should be measured.
      Here we present the core dimensions of the data quality framework developed at
      the Manitoba Centre for Health Policy, a world leader in the use of
      administrative data for research purposes, and provide examples and context for
      the application of these dimensions to conducting data quality evaluations. In
      sharing this framework, our ultimate aim is to promote best practices in rigorous
      data quality assessment among users of administrative data for research.

PMID- 29025003
TI  - Internal carotid artery dissection and Villeret's syndrome.

PMID- 29025006
TI  - Increased risk of subdural hematoma in patients with liver cirrhosis.
AB  - Background: Subdural hematoma (SDH) is associated with a high mortality rate. The
      risk of SDH in cirrhotic patients has not been well studied. Aim: The aim of the
      study was to examine the risk of SDH in cirrhotic patients. Design: A
      retrospective study from a universal insurance claims database of Taiwan.
      Methods: A cohort of 9455 liver cirrhotic patients from 2000 to 2011 and an age
      and sex-matched control cohort of 35992 subjects without cirrhosis were
      identified. The severity of liver cirrhosis was classified into uncomplicated and
      complicated according to presence of complications or not. The incidence and
      hazard ratio of SDH were measured by the end of 2011. Results: The mean follow-up
      years were 4.34+/-3.45 years in the cirrhosis cohort and 6.36+/-3.28 years in the
      non-cirrhosis cohort. The incidence of SDH was 2.73-fold higher in the cirrhosis
      cohort than in the control cohort (29.3 vs. 10.9 per 10000 person-years), with an
      adjusted hazard ratio of 2.73 (95% CI = 2.19-3.42), 2.42 (95% CI = 1.89-3.08),
      and 5.07 (95% CI = 3.38-7.60) in the all liver cirrhosis, the uncomplicated liver
      cirrhosis, and the complicated liver cirrhosis patients compared to the control
      cohort. The adjusted hazard ratios were 2.65 (95% CI 2.06-3.41) for traumatic SDH
      and 3.09 (95% CI 1.91- 5.02) for non-traumatic SDH in liver cirrhosis patients,
      compared to the controls. Conclusions: This study demonstrates that patients with
      cirrhosis are at higher risk of both traumatic and non-traumatic SDH than
      individuals without cirrhosis. The risk increases further in patients with
      complicated liver cirrhosis.

PMID- 29025005
TI  - Correlation of Pain Reduction with fMRI BOLD Response in Osteoarthritis Patients
      Treated with Paracetamol: Randomized, Double-Blind, Crossover Clinical Efficacy
      Study.
AB  - Objective: To assess the relationship between the analgesic efficacy of extended
      release paracetamol (ER-APAP) and brain blood oxygen level-dependent (BOLD)
      signal activation in response to painful stimulation measured by functional
      magnetic resonance imaging (fMRI) in patients with osteoarthritis of the knee.
      Methods: This placebo-controlled, double-blind, crossover, randomized trial (N =
      25) comprised three treatment periods in which patients received four doses of an
      eight-hour ER-APAP caplet (2 x 665 mg), four doses of matched placebo, and no
      treatment. Pain intensity of the knee was measured before and after painful
      stimulation at the knee with osteoarthritis and before and after fMRI. Results:
      ER-APAP significantly reduced prestimulation osteoarthritis knee joint pain
      compared with baseline (P < 0.003) and placebo (P < 0.004). ER-APAP and placebo
      significantly reduced knee joint pain after stimulation (P = 0.014 and P = 0.032,
      respectively); however, pain reduction with ER-APAP was 35% greater than placebo.
      ER-APAP was associated with significant reductions in BOLD signal activation
      after stimulation compared with control in the sensory cortex (P = 0.002) and
      supramarginal gyrus (P = 0.003). Reduction in BOLD signal activation after
      stimulation for placebo was significantly greater than control in the subgenual
      prefrontal cortex (P < 0.001), frontal cortex (P < 0.001), insula (P < 0.003),
      and sensory cortex (P < 0.001). Conclusions: ER-APAP had a significantly greater
      effect than placebo and no treatment in reducing knee pain, which was associated
      with reduced BOLD signal activations in pain pathways, including the sensory
      cortex and supramarginal gyrus. BOLD observations after placebo treatment may
      shed light on the role of the brain regions potentially involved in placebo
      response in clinical trials investigating pain therapies.

PMID- 29025007
TI  - Erratum.

PMID- 29025008
TI  - Cardiopulmonary interactions with beta-blockers and inhaled therapy in COPD.
AB  - Background: Beta-blockers remain underused in patients with chronic obstructive
      pulmonary disease (COPD) and cardiovascular disease. Aim: We compared how
      different inhaled therapies affect tolerability of bisoprolol and carvedilol in
      moderate to severe COPD. Design: A randomized, open label, cross-over study.
      Methods: We compared the cardiopulmonary interactions of bisoprolol 5 mg qd or
      carvedilol 12.5 mg bid for 6 weeks in conjunction with: (i) triple: inhaled
      corticosteroid/long acting beta-agonist/long acting muscarinic antagonist (ICS +
      LABA + LAMA), (ii) dual: ICS + LABA and (iii) ICS alone. Results: Eighteen
      patients completed, all ex-smokers, mean age 65 years, forced expiratory volume
      in 1 s (FEV1) 52% predicted. Bisoprolol and carvedilol produced comparable
      significant reduction in resting and exercise heart rate. FEV1, forced vital
      capacity and lung compliance (AX) were significantly lower with carvedilol vs.
      bisoprolol while taking concomitant ICS/LABA ( P < 0.05) but not ICS/LABA/LAMA.
      Conclusions: In summary, bisoprolol was better tolerated than carvedilol on
      pulmonary function at doses which produced equivalent cardiac beta-1 blockade.
      Worsening of pulmonary function with carvedilol was mitigated by concomitant
      inhaled LAMA (tiotropium) with LABA (formoterol), but not LABA alone. Registered
      at clinicaltrials.gov: NCT01656005.

PMID- 29025004
TI  - Dietary patterns and risk of pancreatic cancer: a systematic review.
AB  - Context: Pancreatic cancer has the highest case fatality rate of all major
      cancers. Objective: A systematic review using PRISMA guidelines was conducted to
      summarize the associations between dietary patterns and risk of pancreatic
      cancer. Data Sources: PubMed and Web of Science databases were searched for case
      control and cohort studies published up to June 15, 2016. Study Selection:
      Eligible studies included a dietary pattern as exposure and pancreatic cancer
      incidence or mortality as outcome and reported odds ratios, hazard ratios, or
      relative risks, along with corresponding 95%CIs. Data Extraction: Important
      characteristics of each study, along with the dietary assessment instrument, the
      component foods or nutrients included in each dietary pattern or the scoring
      algorithm of a priori dietary patterns, were presented. For each dietary pattern
      identified, the estimate of association and the 95%CI comparing the highest
      versus the lowest category from the model with the most covariate adjustment were
      reported. Results: A total of 16 studies were identified. Among the 8 studies
      that examined data-driven dietary patterns, significant positive associations
      were found between pancreatic cancer risk and the Animal Products, Starch Rich,
      and Western dietary patterns, with effect estimates ranging from 1.69 to 2.40.
      Significant inverse relationships were found between risk of pancreatic cancer
      and dietary patterns designated as Fruits and Vegetables, Vitamins and Fiber, and
      Prudent, with effect estimates ranging from 0.51 to 0.55. Eight studies of a
      priori dietary patterns consistently suggested that improved dietary quality was
      associated with reduced risk of pancreatic cancer. Conclusions: Better diet
      quality is associated with reduced risk of pancreatic cancer. The associations
      between dietary patterns and pancreatic cancer were stronger in case-control
      studies than in cohort studies and were stronger among men than among women.

PMID- 29025009
TI  - Crohn's disease: Bamboo joint-like appearance.

PMID- 29025010
TI  - Sperm function, protein phosphorylation, and metabolism differ in mice lacking
      successive sperm-specific glycolytic enzymes.
AB  - Glyceraldehyde 3-phosphate dehydrogenase-S (GAPDHS) and phosphoglycerate kinase 2
      (PGK2), two isozymes restricted to the male germline, catalyze successive steps
      in the glycolytic pathway in mammalian sperm. Although gene targeting of each
      isozyme demonstrated that glycolysis is required for normal sperm motility and
      male fertility, the phenotype of mice lacking GAPDHS is more severe than that of
      mice lacking PGK2. This study examined sperm function, signaling pathways, and
      metabolism to investigate factors that contribute to the phenotypic differences
      between these knockout models. Sperm from the two knockouts exhibited comparable
      deficits in zona binding, in vitro fertilization with or without zona drilling,
      and capacitation-dependent tyrosine phosphorylation. In contrast, signaling and
      metabolic differences were apparent prior to capacitation. Phosphorylation of
      sperm protein phosphatase 1, which has been associated with the acquisition of
      motile capacity during epididymal maturation, was deficient only in GAPDHS-null
      sperm. Carnitine, choline, phosphocholine, and taurine were elevated in sperm
      from both knockouts immediately after collection from the epididymis. However,
      only carnitine levels in PGK2-null sperm were significantly different from wild
      type sperm, while all four metabolites were significantly higher in GAPDHS-null
      sperm. We confirmed that glycolysis is required for robust hyperactivation, but
      found that the motility of PGK2-null sperm improved to levels comparable to wild
      type sperm with pyruvate as the sole metabolic substrate. This nonglycolysable
      substrate did not improve progressive motility in GAPDHS-null sperm. These
      results identify multiple signaling and metabolic defects that are likely
      contributors to male infertility and the absence of progressive sperm motility
      seen in mice lacking GAPDHS.

PMID- 29025011
TI  - Significance of epidermal growth factor receptor signaling for acquisition of
      meiotic and developmental competence in mammalian oocytes.
AB  - The surge in luteinizing hormone (LH) in preovulatory ovarian follicles triggers
      the resumption of oocyte meiosis accompanied by expansion of surrounding cumulus
      cells and ovulation of cumulus-oocyte complexes (COCs) into the oviduct. Over the
      last 15 years, substantial progress has been made in elucidating the key pathways
      by which the LH signal spreads within the preovulatory follicle and in
      identifying the molecules responsible for maintaining oocyte arrest and meiosis
      resumption. It is now clear that the adenylcyclase-mediated rise in intracellular
      cyclic adenosine monophosphate leads to activation of the epidermal growth factor
      receptor (EGFR) network in granulosa and cumulus cells. This signaling network
      can control the transcription of key genes required for cell metabolism, cumulus
      expansion, and oocyte meiosis resumption. In addition, EGFR signaling is involved
      in the regulation of gap junctional communication within follicular somatic
      cells, and in this way it can control the diffusion of meiosis-arresting
      molecules as well as energy substrates into the oocyte. Thus, the proper
      functioning of the follicular EGFR network is a vital precondition for the
      production of matured and developmentally competent oocytes. However, most
      current in vitro maturation systems are based on a culture of COCs isolated from
      growing follicles, in which function of the EGFR network may be insufficient for
      promoting oocyte meiotic and developmental competence. This review focuses on
      research identifying the importance of the EGFR signaling in somatic follicular
      cells for oocyte meiotic and developmental competence, and on special approaches
      to the culture of COCs isolated from growing follicles to promote oocyte quality.

PMID- 29025012
TI  - Enhancing Ear and Hearing Health Access for Children With Technology and
      Connectivity.
AB  - Purpose: Technology and connectivity advances are demonstrating increasing
      potential to improve access of service delivery to persons with hearing loss.
      This article demonstrates use cases from community-based hearing screening and
      automated diagnosis of ear disease. Method: This brief report reviews recent
      evidence for school- and home-based hearing testing in underserved communities
      using smartphone technologies paired with calibrated headphones. Another area of
      potential impact facilitated by technology and connectivity is the use of feature
      extraction algorithms to facilitate automated diagnosis of most common ear
      conditions from video-otoscopic images. Results: Smartphone hearing screening
      using calibrated headphones demonstrated equivalent sensitivity and specificity
      for school-based hearing screening. Automating test sequences with a forced
      choice response paradigm allowed persons with minimal training to offer screening
      in underserved communities. The automated image analysis and diagnosis system for
      ear disease demonstrated an overall accuracy of 80.6%, which is up to par and
      exceeds accuracy rates previously reported for general practitioners and
      pediatricians. Conclusion: The emergence of these tools that capitalize on
      technology and connectivity advances enables affordable and accessible models of
      service delivery for community-based ear and hearing care.

PMID- 29025013
TI  - Commentary: Unusual pancreatic cancer incidence and mortality patterns.

PMID- 29025014
TI  - Reactive oxygen species and protein modifications in spermatozoa.
AB  - Cellular response to reactive oxygen species (ROS) includes both reversible redox
      signaling and irreversible nonenzymatic reactions which depend on the nature and
      concentration of the ROS involved. Changes in thiol/disulfide pairs affect
      protein conformation, enzymatic activity, ligand binding, and protein-protein
      interactions. During spermatogenesis and epididymal maturation, there are ROS
      dependent modifications of the sperm chromatin and flagellar proteins.The
      spermatozoon is regulated by redox mechanisms to acquire fertilizing ability. For
      this purpose, controlled amounts of ROS are necessary to assure sperm activation
      (motility and capacitation). Modifications of the thiol groups redox status of
      sperm proteins are needed for spermatozoon to achieve fertilizing ability.
      However, when ROS are produced at high concentrations, the established oxidative
      stress promotes pathological changes affecting sperm function and leading to
      infertility. Sperm proteins are sensitive to high levels of ROS and suffer
      modifications that impact on motility, capacitation, and the ability of the
      spermatozoon to recognize and bind to the zona pellucida and damage of sperm DNA.
      Thiol oxidation, tyrosine nitration, and S-glutathionylation are highlighted in
      this review as significant redox-dependent protein modifications associated with
      impairment of sperm function and alteration of paternal genome leading to
      infertility. Peroxiredoxins, the primary antioxidant protection in spermatozoa,
      are affected by most of the protein modifications described in this review. They
      play a significant role in both physiological and pathological processes in
      mammalian spermatozoa.

PMID- 29025015
TI  - Lifetime Abuse and Quality of Life among Older People.
AB  - Few studies have evaluated the impact of lifetime abuse on quality of life (QoL)
      among older adults. By using a multinational study authors aimed to assess the
      subjective perception of QoL among people who have reported abuse during the
      course of their lifetime. The respondents (N = 4,467; 2,559 women) were between
      the ages of 60 and 84 years and living in seven European countries (Germany,
      Greece, Italy, Lithuania, Portugal, Spain, and Sweden). Lifetime abuse was
      assessed by using a structured questionnaire that allowed to assess lifetime
      experiences of abuse. QoL was assessed with the World Health Organization Quality
      of Life-Old module. After adjustment for potential confounders, authors found
      that to have had any abusive experience decreased the score of sensory abilities.
      Psychological abuse was associated with lower autonomy and past, present, and
      future activities. Physical abuse with injuries significantly decreased social
      participation. Intimacy was also negatively associated with psychological abuse,
      physical abuse with injury, and sexual abuse. The results of this study provide
      evidence that older people exposed to abuse during their lifetime have a
      significant reduction in QoL, with several QoL domains being negatively affected.

PMID- 29025016
TI  - Cohort Profile: NICHD Fetal Growth Studies-Singletons and Twins.

PMID- 29025017
TI  - Cohort Profile: The Lymphoma Specialized Program of Research Excellence (SPORE)
      Molecular Epidemiology Resource (MER) Cohort Study.

PMID- 29025018
TI  - The association between waterpipe smoking and gastroesophageal reflux disease.
AB  - Background: Unlike cigarettes, there is little information about the association
      between other tobacco products and the risk of gastroesophageal reflux disease
      (GERD) and esophageal adenocarcinoma. Methods: We used the baseline data from the
      Pars Cohort Study conducted in southern Iran. In 2012, 9264 local residents
      between 40 and 75 years old were enrolled, with detailed information about
      lifestyle, including duration and frequency of tobacco use. GERD was defined
      based on questions assessing heartburn and regurgitation in the past 12 months,
      frequency and severity. Associations were calculated by logistic regression
      models adjusted for age, sex, education, cigarettes and body mass index. Results:
      In the study, 25.4% of the participants had severe GERD (interfering with
      participants' routines), 25.1% had frequent GERD (at least once a week) and 11.2%
      had both severe and frequent GERD, all more common among women (p < 0.001); 45.6%
      of women and 28.3% of men smoked waterpipes. Among people not using medications
      against reflux symptoms, there was an association between waterpipe smoking and
      severe [odds ratio (OR) = 1.18; 95% confidence interval (CI):1.04-1.35], frequent
      (OR = 1.16; 95% CI: 1.02-1.32) and severe and frequent reflux (OR = 1.30; 95% CI:
      1.08-1.56). The associations increased with the duration of use, intensity and
      cumulative waterpipe-years, reaching an OR of 1.44 (95% CI: 1.12-1.86) for severe
      and frequent reflux in those who had smoked more than 48 waterpipe-years. There
      was effect modification by sex, and all the associations were only seen among
      women. Conclusion: The increasing trend in the association between cumulative
      waterpipe use and reflux disease among women is particularly important given the
      growing waterpipe tobacco epidemic in many populations.

PMID- 29025019
TI  - Differing molecular response of young and advanced maternal age human oocytes to
      IVM.
AB  - STUDY QUESTION: What effect does maternal age have on the human oocyte's
      molecular response to in vitro oocyte maturation? SUMMARY ANSWER: Although
      polyadenylated transcript abundance is similar between young and advanced
      maternal age (AMA) germinal vesicle (GV) oocytes, metaphase II (MII) oocytes
      exhibit a divergent transcriptome resulting from a differential response to in
      vitro oocyte maturation. WHAT IS KNOWN ALREADY: Microarray studies considering
      maternal age or maturation stage have shown that either of these factors will
      affect oocyte polyadenylated transcript abundance in human oocytes. However,
      studies considering both human oocyte age and multiple stages simultaneously are
      limited to a single study that examined transcript levels for two genes by qPCR.
      Thus, polyadenylated RNA sequencing (RNA-Seq) could provide novel insight into
      age-associated aberrations in gene expression in GV and MII oocytes. STUDY
      DESIGN, SIZE, DURATION: The effect of maternal age (longitudinal analysis) on
      polyadenylated transcript abundance at different stages was analyzed by examining
      single GV and single in vitro matured MII oocytes derived from five young (YNG; <
      30 years; average age 26.8; range 20-29) and five advanced maternal age (AMA;
      >=40 years; average age 41.6 years; range 40-43 years) patients. Thus, a total of
      10 YNG (5 GV and 5 MII) and 10 AMA (5 GV and 5 MII) oocytes were individually
      processed for RNA-Seq analysis. PARTICIPANTS/MATERIALS, SETTINGS, METHODS:
      Patients undergoing infertility treatment at the Colorado Center for Reproductive
      Medicine (Lone Tree, CO, USA) underwent ovarian stimulation with FSH and received
      hCG for final follicular maturation prior to ultrasound guided oocyte retrieval.
      Unused GV oocytes obtained at retrieval were donated for transcriptome analysis.
      Single oocytes were stored (at -80 degrees C in PicoPure RNA Extraction Buffer;
      Thermo Fisher Scientific, USA) immediately upon verification of immaturity or
      after undergoing in vitro oocyte maturation (24 h incubation), representing GV
      and MII samples, respectively. After isolating RNA and generating single oocyte
      RNA-Seq libraries (SMARTer Ultra Low Input RNA HV kit; Clontech, USA), Illumina
      sequencing (100 bp paired-end reads on HiSeq 2500) and bioinformatics analysis
      (CLC Genomics Workbench, DESeq2, weighted gene correlation network analysis
      (WGCNA), Ingenuity Pathway Analysis) were performed. MAIN RESULTS AND THE ROLE OF
      CHANCE: A total of 12 770 genes were determined to be expressed in human oocytes
      (reads per kilobase per million mapped reads (RPKM) > 0.4 in at least three of
      five replicates for a minimum of one sample type). Differential gene expression
      analysis between YNG and AMA oocytes (within stage) identified 1 and 255 genes
      that significantly differed (adjusted P < 0.1 and log2 fold change >1) in
      polyadenylated transcript abundance for GV and MII oocytes, respectively. These
      genes included CDK1, NLRP5 and PRDX1, which have been reported to affect oocyte
      developmental potential. Despite the similarity in transcript abundance between
      GV oocytes irrespective of age, divergent expression patterns emerged during
      oocyte maturation. These age-specific differentially expressed genes were
      enriched (FDR < 0.05) for functions and pathways associated with mitochondria,
      cell cycle and cytoskeleton. Gene modules generated by WGCNA (based on gene
      expression) and patient traits related to oocyte quality (e.g. age and blastocyst
      development) were correlated (P < 0.05) and enriched (FDR < 0.05) for functions
      and pathways associated with oocyte maturation. LARGE SCALE DATA: Raw data from
      this study can be accessed through GSE95477. LIMITATIONS, REASONS FOR CAUTION:
      The human oocytes used in the current study were obtained from patients with
      varying causes of infertility (e.g. decreased oocyte quality and oocyte quality
      independent factors), possibly affecting oocyte gene expression. Oocytes in this
      study were retrieved at the GV stage following hCG administration and the MII
      oocytes were derived by IVM of patient oocytes. Although the approach has the
      benefit of identifying intrinsic differences between samples, it may not be
      completely representative of in vivo matured oocytes. WIDER IMPLICATIONS OF THE
      FINDINGS: Transcriptome profiles of YNG and AMA oocytes, particularly at the MII
      stage, suggest that aberrant transcript abundance may contribute to the age
      associated decline in fertility. STUDY FUNDING/COMPETING INTEREST(S): J.M.R. was
      supported by an Austin Eugene Lyons Fellowship awarded by the University of
      California, Davis. The Eunice Kennedy Shriver National Institute of Child Health
      and Human Development of the National Institutes of Health (awarded to P.J.R.;
      R01HD070044) and the Fertility Laboratories of Colorado partly supported the
      research presented in this manuscript.

PMID- 29025020
TI  - Doctors' views of patient expectations of medical care in Zhejiang Province,
      China.
AB  - Objective: Physicians' prescribing patterns may be influenced by how they
      perceive their patients' expectations of medical care. This study explored
      doctors' perceptions of patient expectations of medical care. Design: Qualitative
      interviews and a cross-sectional survey (September 2014-September 2015). Setting:
      Primary- and tertiary-care facilities in Zhejiang province, China. Participants:
      Primary care practitioners (PCPs) and hospital specialists. Main outcomes:
      Perceived patients' expectations. Results: Seven focus groups and 21 individuals
      were interviewed. Questionnaires were completed by 460 PCPs and 651 specialists
      (response rate: 78%). About 36.8% of doctors reported generating profit for the
      facility at which they practiced as a foremost consideration. Participants
      perceived patients as holding high expectations of clinical performance and use
      of medical products. Respondents perceived that their patients expected either
      drug prescriptions (48.2%) or intravenous (IV) therapy (45.2%). Perceived patient
      expectations of an arrangement of tests and consultation fee refunds if no
      prescriptions were made were reported by 29.7 and 22.7%, respectively. Doctors
      reported feeling undervalued and disrespected when patients requested
      consultation fee refunds. Compared to those who did not report a need for profit
      making, doctors who did were significantly more likely to perceive that their
      patients expected medication-based treatments (AOR = 1.62, P < 0.001), IV therapy
      (AOR = 1.32, P = 0.037), the arrangement of tests (AOR = 2.06, P < 0.001), and
      consultation fee refunds when no prescriptions were made (AOR = 1.92, P < 0.001).
      Conclusions: Most doctors believed that patients had high expectations. Workplace
      profit-orientation demonstrated a strong association with doctors' perceptions.

PMID- 29025021
TI  - Misconceptions on the use of MR-Egger regression and the evaluation of the InSIDE
      assumption.

PMID- 29025022
TI  - Actin brings chromosomes up to speed during oocyte maturation.

PMID- 29025023
TI  - "Why Do I Feel This Pain?" B-Mode and Power Doppler Ultrasound Found the Answer:
      A Neurovascular Conflict.

PMID- 29025024
TI  - Implementing prescription drug monitoring and other clinical decision support for
      opioid risk mitigation in a military health care setting: a qualitative
      feasibility study.
AB  - Objective: Chronic noncancer pain is a highly prevalent condition among service
      members returning from deployment overseas. The US Army has a higher rate of
      opioid misuse than the civilian population. Although most states and many health
      care systems have implemented prescription drug monitoring programs (PDMPs) or
      other clinician decision support (CDS) to aid providers in delivering guideline
      recommended opioid therapy, similar tools are lacking in military health
      settings. Materials and Methods: We conducted a pre-implementation feasibility
      and needs assessment guided by the Promoting Action Research in Health Services
      framework. Twenty-six semistructured interviews were conducted with providers
      from a large military health system (MHS) to assess baseline knowledge and
      practices in opioid risk mitigation and providers' preferences and needs for a
      military-based PDMP or other CDS. Results: Military health care providers
      reported complex decision-making around opioid prescribing and monitoring, varied
      knowledge and use of existing clinical informatics, and concerns about the
      feasibility of implementing a military-based PDMP in their context. However,
      providers indicated a need for training and CDS to support opioid risk mitigation
      for their patients. Discussion: This article describes providers' knowledge and
      behaviors around opioid risk mitigation in the MHS, and views on the potential
      usefulness of a military-based PDMP or other CDS. This pre-implementation study
      provides a model for using qualitative methods to assess feasibility and inform
      planning and development of CDS in complex health care settings. Conclusion:
      Military providers were skeptical regarding the feasibility of MHS-based PDMP
      implementation, but provided important recommendations for CDS to support safe
      and appropriate opioid prescribing in military health care.

PMID- 29025025
TI  - The importance of historical residential address information in longitudinal
      studies using administrative health data.
AB  - Background: When information on changes in address or migration of people to or
      from a study jurisdiction is unavailable in longitudinal studies, issues relating
      to loss-to-follow-up and misclassification bias may result. This study
      investigated how estimations of associations between general practitioner (GP)
      contact and hospital use were affected by incomplete address and migration data.
      Methods: This was a retrospective population-based cohort study of Western
      Australians from 1990 to 2004. Linked administrative data including mortality
      records, hospital admissions, primary care and Electoral Roll records were used.
      Regularity of GP contact, based on the variance of the number of days between GP
      visits, was calculated for each person-year. Outcomes were the number and costs
      (A$2014) of diabetes-related hospital admissions in the following year. Models
      were estimated separately for cohorts where (i) postcode was ascertained at study
      commencement and held constant, and (ii) postcode and residency within Western
      Australia were updated with each change of address recorded on the Electoral Roll
      over the study period. Results: Updating address data reduced total person-years
      by 11% and changed the distribution of covariates. Estimations of associations
      between patterns of GP contact and number of hospitalizations changed; the
      incidence rate ratios measuring the relationship with the most regular GP contact
      (baseline of those with <2 GP visits) changed from 0.81 [95% confidence interval
      (CI) 0.66-1.00] to 0.42 (95% CI 0.33-0.53) after updating postcode information.
      Impacts on cost models were smaller, though still statistically significant.
      Conclusions: Longitudinal studies using administrative data may report biased
      results if they ignore address changes and migration. Researchers should attempt
      to link to these data wherever possible, or choose study designs which these
      issues are less likely to affect. Custodians should be aware that such data can
      be vital to high quality research.

PMID- 29025026
TI  - Response to 'Vitamin B12 deficiency may coexist with endocrine causes of
      hyperpigmentation'.

PMID- 29025027
TI  - Maternal melatonin or agomelatine therapy prevents programmed hypertension in
      male offspring of mother exposed to continuous light.
AB  - Hypertension can originate from early-life insults, whereas maternal melatonin
      therapy can be protective in a variety of models of programmed hypertension. We
      hypothesize that melatonin or melatonin receptor agonist agomelatine can prevent
      programmed hypertension in adult offspring induced by maternal exposure to
      continuous light. Female Sprague-Dawley pregnant rats randomly divided into four
      groups: controls, rats exposed to continuous light, exposed to continuous light
      plus treated with agomelatine (50 mg/day i.p.), and exposed to continuous light
      plus treated with 0.01% melatonin in drinking water throughout pregnancy and
      lactation period. Male offspring (n = 10/group) from three litters were examined
      at 12 weeks of age. Maternal continuous light exposure-induced hypertension in
      male offspring, which was prevented by melatonin or agomelatine therapy.
      Continuous light exposure did not affect melatonin pathway in adult offspring
      kidney. Genes that belong to the renin-angiotensin system (RAS), sodium
      transporters, AMP-activated protein kinase pathway, and circadian rhythm were
      potentially involved in the maternal exposure to continuous light-induced
      programmed hypertension. Maternal agomelatine therapy decreased Ace expression
      but increased Agtr2 and Mas1. Maternal melatonin therapy prevented the increases
      of Slc9a3, Slc12a3, and Atp1a1 expression induced by maternal continuous light
      exposure. In conclusion, maternal melatonin or agomelatine therapy prevents
      programmed hypertension induced by maternal exposure to continuous light.
      Agomelatine and melatonin reprogram the RAS and sodium transporters
      differentially, to prevent negative programming of continuous light. Our data
      highlight candidate genes and pathways in renal programming as targets for
      therapeutic approaches to prevent programmed hypertension caused by early-life
      disturbance of the circadian rhythm.

PMID- 29025029
TI  - CT coronary imaging-a fast evolving world.
AB  - Computed tomography (CT) has become an important modality in the evaluation of
      coronary artery disease (CAD). The tremendous technological advances in CT in the
      last two decades has made it possible to obtain high quality images of coronary
      arteries with high spatial and temporal resolutions. Multiple trials have
      confirmed the accuracy of CT compared to invasive catheter angiography. CT is
      also able to evaluate beyond the lumen in characterizing and quantifying
      atherosclerotic plaques, including evaluation of high risk features. Although CTA
      has low specificity in identification of lesion-specific ischemia, functional
      techniques are now possible such as CT myocardial perfusion and CT-fractional
      flow reserve (FFR) which evaluate the hemodynamic significance of stenosis and
      help with revascularization strategies. Multi-energy CT provides additional
      information beyond what is possible with a conventional CT and is useful in
      variety of clinical applications, including myocardial perfusion imaging, lesion
      characterization and low contrast studies. Large trials have confirmed the
      ability of CT to predict major adverse cardiovascular events and recent trials
      have even demonstrated improved clinical outcomes by using CT for the evaluation
      of CAD. CT is also useful in structural heart disease and 3 D printing is now
      increasingly used for surgical/interventional planning. Machine learning is
      evolving rapidly and is likely to impact diagnosis and management.

PMID- 29025030
TI  - Third-Degree Skin Burn from Conventional Radiofrequency Ablation of the
      Inferiomedial Genicular Nerve.

PMID- 29025031
TI  - Anal cancer: different epidemiological and clinical definitions.

PMID- 29025034
TI  - An environmental scan of shared access to patient portals.
AB  - We sought to understand the comprehensiveness of consumer-oriented information
      describing the availability of shared access to adult patient portals from
      publicly reported information on institutional websites of 20 large and
      geographically diverse health systems. All 20 health systems reported that they
      offer patients the ability to share access to their patient portal account with a
      family member or friend; however, the comprehensiveness of information regarding
      registration procedures, features, and terminology varied widely. Half of the
      systems (n = 10) reported having shared access available on their patient portal
      registration webpage. Few systems (n = 2) reported affording patients the ability
      to differentiate specific role-based privileges. No systems reported uptake of
      shared access among adult patients, which was variably described as "proxy,"
      "caregiver," "parental," or "delegate" access. Findings suggest that engaging
      families through health information technology will require greater efforts to
      promote awareness and differentiate privileges that respect patients' choice and
      control in information-sharing preferences.

PMID- 29025035
TI  - Regression of the male reproductive tract in the female embryo is regulated by
      the orphan nuclear receptor COUP-TFII.

PMID- 29025033
TI  - Heavier smoking increases coffee consumption: findings from a Mendelian
      randomization analysis.
AB  - Background: There is evidence for a positive relationship between cigarette and
      coffee consumption in smokers. Cigarette smoke increases metabolism of caffeine,
      so this may represent a causal effect of smoking on caffeine intake. Methods: We
      performed Mendelian randomization analyses in the UK Biobank (N = 114 029), the
      Norwegian HUNT study (N = 56 664) and the Copenhagen General Population Study
      (CGPS) (N = 78 650). We used the rs16969968 genetic variant as a proxy for
      smoking heaviness in all studies and rs4410790 and rs2472297 as proxies for
      coffee consumption in UK Biobank and CGPS. Analyses were conducted using linear
      regression and meta-analysed across studies. Results: Each additional cigarette
      per day consumed by current smokers was associated with higher coffee consumption
      (0.10 cups per day, 95% CI: 0.03, 0.17). There was weak evidence for an increase
      in tea consumption per additional cigarette smoked per day (0.04 cups per day,
      95% CI: -0.002, 0.07). There was strong evidence that each additional copy of the
      minor allele of rs16969968 (which increases daily cigarette consumption) in
      current smokers was associated with higher coffee consumption (0.16 cups per day,
      95% CI: 0.11, 0.20), but only weak evidence for an association with tea
      consumption (0.04 cups per day, 95% CI: -0.01, 0.09). There was no clear evidence
      that rs16969968 was associated with coffee or tea consumption in never or former
      smokers or that the coffee-related variants were associated with cigarette
      consumption. Conclusions: Higher cigarette consumption causally increases coffee
      intake. This is consistent with faster metabolism of caffeine by smokers, but
      could also reflect a behavioural effect of smoking on coffee drinking.

PMID- 29025036
TI  - Pseudomembranous colitis.

PMID- 29025037
TI  - Association between workarounds and medication administration errors in bar-code
      assisted medication administration in hospitals.
AB  - Objective: To study the association of workarounds with medication administration
      errors using barcode-assisted medication administration (BCMA), and to determine
      the frequency and types of workarounds and medication administration errors.
      Materials and Methods: A prospective observational study in Dutch hospitals using
      BCMA to administer medication. Direct observation was used to collect data.
      Primary outcome measure was the proportion of medication administrations with one
      or more medication administration errors. Secondary outcome was the frequency and
      types of workarounds and medication administration errors. Univariate and
      multivariate multilevel logistic regression analysis were used to assess the
      association between workarounds and medication administration errors. Descriptive
      statistics were used for the secondary outcomes. Results: We included 5793
      medication administrations for 1230 inpatients. Workarounds were associated with
      medication administration errors (adjusted odds ratio 3.06 [95% CI: 2.49-3.78]).
      Most commonly, procedural workarounds were observed, such as not scanning at all
      (36%), not scanning patients because they did not wear a wristband (28%),
      incorrect medication scanning, multiple medication scanning, and ignoring alert
      signals (11%). Common types of medication administration errors were omissions
      (78%), administration of non-ordered drugs (8.0%), and wrong doses given (6.0%).
      Discussion: Workarounds are associated with medication administration errors in
      hospitals using BCMA. These data suggest that BCMA needs more post-implementation
      evaluation if it is to achieve the intended benefits for medication safety.
      Conclusion: In hospitals using barcode-assisted medication administration,
      workarounds occurred in 66% of medication administrations and were associated
      with large numbers of medication administration errors.

PMID- 29025032
TI  - Physical activity, mediating factors and risk of colon cancer: insights into
      adiposity and circulating biomarkers from the EPIC cohort.
AB  - Background: There is convincing evidence that high physical activity lowers the
      risk of colon cancer; however, the underlying biological mechanisms remain
      largely unknown. We aimed to determine the extent to which body fatness and
      biomarkers of various biologically plausible pathways account for the association
      between physical activity and colon cancer. Methods: We conducted a nested case
      control study in a cohort of 519 978 men and women aged 25 to 70 years followed
      from 1992 to 2003. A total of 713 incident colon cancer cases were matched, using
      risk-set sampling, to 713 controls on age, sex, study centre, fasting status and
      hormonal therapy use. The amount of total physical activity during the past year
      was expressed in metabolic equivalent of task [MET]-h/week. Anthropometric
      measurements and blood samples were collected at study baseline. Results: High
      physical activity was associated with a lower risk of colon cancer: relative risk
      >=91 MET-h/week vs <91 MET-h/week = 0.75 [95% confidence interval (CI): 0.57 to
      0.96]. In mediation analyses, this association was accounted for by waist
      circumference: proportion explained effect (PEE) = 17%; CI: 4% to 52%; and the
      biomarkers soluble leptin receptor (sOB-R): PEE = 15%; 95% CI: 1% to 50% and 5
      hydroxyvitamin D (25[OH]D): PEE = 30%; 95% CI: 12% to 88%. In combination, these
      factors explained 45% (95% CI: 20% to 125%) of the association. Beyond waist
      circumference, sOB-R and 25[OH]D additionally explained 10% (95% CI: 1%; 56%) and
      23% (95% CI: 6%; 111%) of the association, respectively. Conclusions: Promoting
      physical activity, particularly outdoors, and maintaining metabolic health and
      adequate vitamin D levels could represent a promising strategy for colon cancer
      prevention.

PMID- 29025028
TI  - Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium.

PMID- 29025040
TI  - A note on the use of Egger regression in Mendelian randomization studies.

PMID- 29025041
TI  - Trigger Points, Pressure Pain Hyperalgesia, and Mechanosensitivity of Neural
      Tissue in Women with Chronic Pelvic Pain.
AB  - Objectives: This study aims to evaluate the presence of myofascial trigger points
      (TrPs), widespread pressure pain sensitivity, and mechanosensitivity of neural
      tissue in women with chronic pelvic pain. Design: Case-control study. Setting:
      Faculty of Health Sciences. Subjects: Forty women with chronic pelvic pain
      between age 18 and 60 years and 40 matched healthy controls were included in the
      study. Methods: TrPs were bilaterally explored in gluteus maximus, gluteus
      medius, gluteus minimus, quadratus lumborum, and adductor magnus muscles. The
      referred pain reproduced lumbopelvic symptoms. Pressure pain thresholds (PPTs)
      were also bilaterally assessed over the Pfannenstiel incision point on the
      abdominal, C5-C6 zygapophyseal joint, second metacarpal, and tibialis anterior
      muscle. Mechanosensitivity of neural tissue was assessed with the neurodynamics
      tests of slump and the straight-leg raising. Results: Significant between-group
      differences were found in TrP presence in patients with chronic pelvic pain (P <
      0.001) compared with those included in the control group. Widespread pressure
      pain hyperalgesia was also found, with PPTs significantly reduced in the points
      assessed. Neurodynamics show a significantly decreased value in women with CPP.
      Conclusions: Patients with chronic pelvic pain presented a high percentage of
      TrPs that reproduce their symptoms. Patients also showed a widespread pressure
      pain hyperalgesia and more mechanosensitive neural tissue due to a decrease on
      the range of motion related to neurodynamics.

PMID- 29025039
TI  - Rehabilitative post-acute care for stroke patients delivered by per-diem payment
      system in different hospitalization paths: A Taiwan pilot study.
AB  - Objective: To explore how post-acute care (PAC) for stroke patients delivered by
      per-diem payment system in varying hospitalization paths affects medical care
      utilization and functional status. Design, setting and patients: A longitudinal
      prospective cohort study of 181 acute stroke patients in a southern Taiwan
      hospital and patients were separated into two groups: patients transferred from
      regional hospitals (group 1) and patients referred from medical centers (group
      2). Intervention: The intervention was a hospital based, function oriented, 3- to
      12-weeks rehabilitative PAC intervention for patients with cerebrovascular
      diseases. Measurements: Barthal Index, Functional Oral Intake Scale, Instrumental
      Activities of Daily Living Scale, EuroQoL Quality of Life Scale, and Berg Balance
      Scale. Results: The average duration between day of stroke onset and day of
      admission to PAC ward was significantly (P < 0.001) shorter in group 1 (9.88
      days) compared to group 2 (17.11 days). The average duration of PAC was also
      significantly (P < 0.01) shorter in group 1 (25.51 days) compared to group 2
      (34.11 days). Finally, the average cost of PAC under per-diem payment was
      significantly lower (P < 0.01) in group 1 (US$2637) compared to group 2
      (US$3450). Functional status significantly (P < 0.05) improved in patients who
      had received rehabilitative PAC. However, functional status did not significantly
      differ between the two groups. Conclusions: The most effective way to reduce the
      costs of PAC for stroke patients is to minimize the duration of their hospital
      stay before transfer to rehabilitative PAC. Because it substantially reduces
      medical costs, rehabilitative PAC should be considered standard care for stroke
      patients.

PMID- 29025038
TI  - Selective progesterone receptor modulators for fertility preservation in women
      with symptomatic uterine fibroids.
AB  - Uterine fibroids (UFs, AKA leiomyoma) are the most important benign neoplastic
      threat to women's health, with costs up to hundreds of billions of health care
      dollars worldwide. Uterine fibroids caused morbidities exert a tremendous health
      toll, impacting the quality of life of women of all ethnicities, especially women
      of color. Clinical presentations include heavy vaginal bleeding, pelvic pain,
      bulk symptoms, subfertility, and obstetric complications. Current management
      strategies heavily lean toward surgical procedures; nonetheless, the choice of
      treatment is generally subject to patient's age and her desire to preserve future
      fertility. Women with UF who desire to maintain future fertility potential face a
      dilemma because of the limited treatment choices that are currently available to
      help them achieve that goal. Recently, ulipristal acetate the first of the
      promising family of oral selective progesterone receptor modulators has been
      approved for UF treatment in Europe, Canada, and several other countries and is
      under review for possible approval in the USA. In this review article, we discuss
      recent advances in the management options against UF with a bend toward oral
      effective long-term treatment alternatives who are particularly suited for those
      seeking to preserve their future fertility potential. We also explore the
      transformative concept of primary and secondary UF prevention using these new
      anti-UF agents. We envision a remarkable shift in the management of UF in future
      years from surgical/invasive treatment to orally administrated options; clearly,
      this potential shift will require additional intense clinical research.

PMID- 29025043
TI  - Cohort Profile: The HIV Atlanta Veterans Affairs Cohort Study (HAVACS).

PMID- 29025042
TI  - Stage-specific follicular extracellular vesicle uptake and regulation of bovine
      granulosa cell proliferation.
AB  - Follicular fluid within ovarian antral follicles contains numerous factors, which
      influence the development of a healthy oocyte including nucleic acids, steroids,
      proteins, and extracellular vesicles (EVs). Current evidence indicates that
      follicular EVs promote changes in cellular gene expression and support cumulus
      oocyte complex expansion in vitro. In this study, we found EVs from different
      sized follicles differentially stimulate granulosa cell proliferation and this
      could be explained by both the differential contents associated, on or within the
      vesicles and by the preferential uptake of EVs dependent on follicle size from
      which they were isolated. Antibody array and inhibitor studies indicated that the
      Src, PI3K/Akt, and MAPK signaling pathways mediate the stimulatory effects of EVs
      on granulosa cell proliferation. This study demonstrates for the first time that
      EVs isolated from follicular fluid are capable of stimulating granulosa cell
      proliferation and that this stimulatory response is associated with the size of
      antral follicle from which the EVs originated. The study further also provides
      the first evidence that vesicles released by small antral follicles are
      preferentially taken up when compared to those isolated from large follicles,
      suggesting that vesicular surface proteins change during follicular maturation.

PMID- 29025044
TI  - International Consensus on Diagnostic Criteria and Clinical Considerations of
      Myofascial Trigger Points: A Delphi Study.
AB  - Objective: There is no consensus on the essential diagnostic criteria for
      diagnosing a trigger point (TrP). In fact, a variety of diagnostic criteria are
      currently being used. Our aim was to conduct a Delphi panel to achieve an
      international consensus on the cluster of criteria needed for the TrP diagnosis
      to reach a consensus on the definition of active and latent TrPs and to clarify
      different clinical considerations about TrPs. Methods: Following international
      guidelines, an international three-round Delphi survey was conducted. Questions
      were created based on a systematic literature search of the diagnostic criteria
      for TrPs. Results: Sixty experts from 12 countries completed all rounds of the
      survey. A cluster of three diagnostic criteria was proposed as essential for the
      TrP diagnosis: a taut band, a hypersensitive spot, and referred pain. Eighty
      percent of the experts agreed that the referred pain elicited by a TrP can
      include different sensory sensations and not just pain, that is, pain spreading
      to a distant area, deep pain, dull ache, tingling, or burning pain. Eighty-four
      percent of the international experts consistently answered that the main clinical
      differences between active and latent TrPs are the reproduction of any of the
      symptoms experienced by a patient and the recognition of pain. No specific
      location of the pain referral area and TrP location should be expected.
      Conclusions: This Delphi panel has produced an expert-based standardized
      definition of a TrP with a discussion of the clinical components, including the
      definition of referred pain and the difference between active and latent TrPs,
      thereby providing a foundation for future research in MPS.

PMID- 29025045
TI  - Clinical features and outcomes in secondary adult hemophagocytic
      lymphohistiocytosis.
AB  - Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome
      characterized by an infrequent but immune-mediated life-threatening disease, with
      confusing clinical manifestations, rapidly deteriorating health, high morbidity
      and mortality and challenging diagnosis. Aim: The purpose of this study was to
      improve the recognition and understanding of HLH. Design: Retrospective
      observational cross-sectional study. Methods: Data were collected for all cases
      of adult patients diagnosed with HLH in a large cohort managed at a single
      medical center from January 2011 to December 2015. Results: The median age was 52
      years (range 18-90 years) and 123 (60.0%) were male. Over 95% patients manifested
      fever, hyperferritinemia and elevated lactate dehydrogenase. Underlying triggers
      of HLH were as follows: 119 (58.0%) malignancies, 83 (40.5%) infections, 14
      (6.8%) unknown triggers and 14 (6.8%) autoimmune disorders. The median overall
      survival was 55 days. And elderly patients (age >=60 years) had a markedly worse
      survival compared with young patients (age <60 years) (median overall survival 24
      days vs. 159 days, respectively; P <0.001). In a multivariable analysis, platelet
      <40 * 109/l (HR = 2.534; 95% CI 1.152-5.573; P = 0.021), PT prolonged >3 s (HR =
      1.909; 95% CI 1.127-3.234; P = 0.016) and malignancy (HR = 1.614; 95% CI 1.008
      2.582; P = 0.046) were correlated with poor survival. Conclusion: HLH adult
      patients had very complex clinical manifestations as well as underlying diseases.
      Patients with PLT <40 *109/l, PT prolonged >3 s and malignancy had inferior
      survival. It is of great importance to improve our understanding of this
      syndrome.

PMID- 29025046
TI  - Decreased insulin secretion in pregnant rats fed a low protein diet.
AB  - Low protein (LP) diet during pregnancy leads to reduced plasma insulin levels in
      rodents, but the underlying mechanisms remain unclear. Glucose is the primary
      insulin secretagogue, and enhanced glucose-stimulated insulin secretion (GSIS) in
      beta cells contributes to compensation for insulin resistance and maintenance of
      glucose homeostasis during pregnancy. In this study, we hypothesized that plasma
      insulin levels in pregnant rats fed LP diet are reduced due to disrupted GSIS of
      pancreatic islets. We first confirmed reduced plasma insulin levels, then
      investigated in vivo insulin secretion by glucose tolerance test and ex vivo GSIS
      of pancreatic islets in the presence of glucose at different doses, and KCl,
      glibenclamide, and L-arginine. Main findings include (1) plasma insulin levels
      were unaltered on day 10, but significantly reduced on days 14-22 of pregnancy in
      rats fed LP diet compared to those of control (CT) rats; (2) insulin sensitivity
      was unchanged, but glucose intolerance was more severe in pregnant rats fed LP
      diet; (3) GSIS in pancreatic islets was lower in LP rats compared to CT rats in
      the presence of glucose, KCl, and glibenclamide, and the response to L-arginine
      was abolished in LP rats; and (4) the total insulin content in pancreatic islets
      and expression of Ins2 were reduced in LP rats, but expression of Gcg was
      unaltered. These studies demonstrate that decreased GSIS in beta cells of LP rats
      contributes to reduced plasma insulin levels, which may lead to placental and
      fetal growth restriction and programs hypertension and other metabolic diseases
      in offspring.

PMID- 29025047
TI  - The representativeness of eligible patients in type 2 diabetes trials: a case
      study using GIST 2.0.
AB  - Objective: The population representativeness of a clinical study is influenced by
      how real-world patients qualify for the study. We analyze the representativeness
      of eligible patients for multiple type 2 diabetes trials and the relationship
      between representativeness and other trial characteristics. Methods: Sixty-nine
      study traits available in the electronic health record data for 2034 patients
      with type 2 diabetes were used to profile the target patients for type 2 diabetes
      trials. A set of 1691 type 2 diabetes trials was identified from
      ClinicalTrials.gov, and their population representativeness was calculated using
      the published Generalizability Index of Study Traits 2.0 metric. The
      relationships between population representativeness and number of traits and
      between trial duration and trial metadata were statistically analyzed. A focused
      analysis with only phase 2 and 3 interventional trials was also conducted.
      Results: A total of 869 of 1691 trials (51.4%) and 412 of 776 phase 2 and 3
      interventional trials (53.1%) had a population representativeness of <5%. The
      overall representativeness was significantly correlated with the
      representativeness of the Hba1c criterion. The greater the number of criteria or
      the shorter the trial, the less the representativeness. Among the trial metadata,
      phase, recruitment status, and start year were found to have a statistically
      significant effect on population representativeness. For phase 2 and 3
      interventional trials, only start year was significantly associated with
      representativeness. Conclusions: Our study quantified the representativeness of
      multiple type 2 diabetes trials. The common low representativeness of type 2
      diabetes trials could be attributed to specific study design requirements of
      trials or safety concerns. Rather than criticizing the low representativeness, we
      contribute a method for increasing the transparency of the representativeness of
      clinical trials.

PMID- 29025048
TI  - Meta-analysis of occupational exposures in the rubber manufacturing industry and
      risk of cancer.
AB  - Background: Occupational exposures in the rubber manufacturing industry showed an
      increased risk of cancer and have been classified as a group 1 carcinogen,
      largely from studies on workers employed before 1950s. Cancer sites considered as
      causally associated are bladder, lung and stomach, and leukaemia. Recent studies
      did not report an increased risk of cancer. Methods: A meta-analysis was
      conducted on observational studies published until April 2016 on occupational
      exposures in the rubber manufacturing industry and risk of cancer. Case-control
      and cohort studies were included. Random effect models were used. Heterogeneity
      and publication bias were evaluated. Stratified analyses were conducted on study
      characteristics. Results: The literature search identified 46 cohorts and 59 case
      control studies. An increased risk was found for bladder cancer [standardised
      incidence ratio (SRR) = 1.36; 95% confidence interval (CI) 1.18, 1.57], leukaemia
      (SRR = 1.29; 95% CI 1.11, 1.52), lymphatic and haematopoietic system (SRR = 1.16;
      95% CI 1.02, 1.31) and larynx cancer (SRR = 1.46; 95% CI 1.10, 1.94). For lung
      cancer, a borderline statistically significant increased risk was identified (SRR
      = 1.08; 95% CI 0.99, 1.17). No association was found for stomach cancer (SRR =
      1.06; 95% CI 0.95, 1.17). In stratified analyses, risks of cancer were not
      increased for workers employed after 1960 for bladder cancer (SRR = 1.06; 95% CI
      0.66, 1.71), lung cancer (SRR = 0.94; 95% CI 0.68, 1.29) or leukaemia (SRR =
      0.92; 95% CI 0.62, 1.36). Conclusions: Risk of bladder cancer, lung cancer,
      leukaemia and larynx cancer were increased among workers in rubber industry.
      Evidence of elevated risks was no longer seen for bladder cancer, lung cancer or
      leukemia among workers first employed after 1960.

PMID- 29025050
TI  - An outbreak of community-acquired pseudomonas aeruginosa pneumonia in a setting
      of high water stress.

PMID- 29025049
TI  - Senior services in US hospitals and readmission risk in the Medicare population.
AB  - Background: There is a little understanding of the association between hospital
      organizational characteristics and hospital readmissions. We previously developed
      a Senior Care Services Scale (SCSS) that describes hospital availability of
      services relevant to the care of older adults. Objective: Determine whether
      hospitals' SCSS scores were associated with risk of readmission among Medicare
      beneficiaries. Design: Retrospective cohort analysis. Setting and Participants:
      Medicare beneficiaries >=65 years of age (n = 3 553 367), admitted to 5568 US
      acute-care hospitals in 2006, discharged alive. Medicare data were linked to the
      American Hospital Association database of hospital characteristics. Measurements:
      All-cause non-elective hospital readmission, or death without readmission, within
      30 days of hospital discharge. Results: We examined the association between high
      and low scores of each of two hospital SCSS service groups: inpatient specialty
      care (IP) and post-acute (PA) community care. There was no association between
      high IP scores and readmission (RR 1.00, 95% CI 0.98-1.02). Older adults admitted
      to hospitals with high PA scores had lower risk of experiencing hospital
      readmission when compared to older adults admitted to hospitals with low PA
      scores (RR 0.97, 95% CI 0.95-0.98). High PA scores were associated with increased
      mortality (RR 1.09, 95% CI 1.06-1.13). In sensitivity analyses exploring
      relationships at 90 days, both the IP and PA subcomponents were associated with
      older adults' reduced risk of hospital readmission (IP: RR 0.97, 95% CI 0.95
      0.99; PA: RR 0.97, 95% CI 0.95-0.99). Conclusion: Senior services at the hospital
      level represents a modifiable risk factor with important impact. Employing
      organization-level characteristics in readmission risk prediction tools should be
      expanded.

PMID- 29025051
TI  - Integrating Behavioral Health Risk Assessment into Centralized Intake for
      Maternal and Child Health Services.
AB  - Effectively promoting women's health during and around the time of pregnancy
      requires early, nonstigmatizing identification and assessment of behavioral
      health risks (such as depression, substance use, smoking, and interpersonal
      violence) combined with timely linkage to community support and specialized
      interventions. This article describes an integrated approach to behavioral health
      risk screening woven into a point of first contact with the health care delivery
      system: centralized intake for maternal and child health home visiting programs.
      Behavioral Health Integrated Centralized Intake is a social work-informed,
      community-designed approach to screening, brief intervention, and service linkage
      targeting communities at high risk for fetal and infant mortality. Women enrolled
      in this study were receptive to holistic risk screening as well as guided
      referral for both home visiting support and specialized mental health
      interventions. Results from this multi-community study form the foundation for
      strengths-based, social work-informed enhancements to community health promotion
      programs.

PMID- 29025052
TI  - Ultrasound double contour sign and gout.

PMID- 29025053
TI  - Commentary: Does early cannabis initiation reduce educational attainment? New
      contributions and unanswered questions.

PMID- 29025054
TI  - Presence of polycystic ovary syndrome is associated with longer anogenital
      distance in adult Mediterranean women.
AB  - STUDY QUESTION: Is polycystic ovary syndrome (PCOS) associated with anogenital
      distance (AGD), a biomarker of fetal androgen exposure, in adult Mediterranean
      women? SUMMARY ANSWER: Longer AGD is associated with PCOS in adult Mediterranean
      women. WHAT IS KNOWN ALREADY: AGD is a biomarker of prenatal androgen milieu.
      Human observational studies have reported that associations between AGD and
      reproductive parameters in both sexes. Exposure of the female fetus to
      intrauterine androgens may be a risk factor for PCOS in adulthood. STUDY DESIGN,
      SIZE, DURATION: This was a case-control study of 126 women with PCOS and 159
      controls between September 2014 and May 2016. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: Cases were attending the gynecology unit of the 'Virgen de la Arrixaca'
      University Clinical Hospital (Murcia, Spain), and were diagnosed following the
      Rotterdam criteria. Phenotypic subtypes of PCOS were also assessed. Both
      prevalent and incident (newly diagnosed) cases were included. Controls were women
      without PCOS attending the gynecological outpatient clinic for routine
      gynecological exams. All women completed health questionnaires, and underwent
      physical and gynecological examinations, including transvaginal ultrasound and
      blood draw. We obtained measures from the anterior clitoral surface to the upper
      verge of the anus (AGDAC), and from the posterior fourchette to the upper verge
      of the anus (AGDAF). Gynecologists performing the AGD measures were blind to the
      status of the patients. We used unconditional multiple logistic regression to
      evaluate the association between AGD measurements and PCOS while accounting for
      relevant covariates and confounders, such as BMI, age and episiotomy. MAIN
      RESULTS AND THE ROLE OF CHANCE: Cases showed significantly longer AGDAF and AGDAC
      compared to controls in bivariate analyses (P-values < 0.05). In the final
      adjusted models, AGDAC, but not AGDAF, was associated with the presence of PCOS
      (P-values = 0.002-0.008). Women with AGDAC in the upper compared to the lowest
      tertile were 2.9-times (95% CI 1.4-5.9; P-trend = 0.008) more likely to have
      PCOS. AGDAC measures were also significantly associated with all of the different
      phenotypic subtypes of PCOS (ORs = 3.1-5.1; P-values < 0.05). LIMITATIONS REASONS
      FOR CAUTION: We took into account known and suspected covariates and confounders,
      but the possibility of chance findings or residual confounding should be noted.
      As with all observational studies, causal inference is limited, and study
      selection and information bias should not be ruled out. WIDER IMPLICATIONS OF THE
      FINDINGS: Our results support the hypothesis that PCOS has an intrauterine
      origin, and that the hormonal environment in which the fetus develops may be
      highly relevant. STUDY FUNDING/COMPETING INTEREST: This work was supported by the
      Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (ISCIII)
      (AES, Accion Estrategica en Salud), grant No. PI13/01237, and The Seneca
      Foundation, Murcia Regional Agency of Science and Technology, grant No.
      19443/PI/14. There are no competing interests. TRIAL REGISTRATION NUMBER: Not
      applicable.

PMID- 29025056
TI  - ADF: Abuse-Deterrent Formulation or Another Disillusioned Formulation?

PMID- 29025055
TI  - Frozen embryo transfer: a review on the optimal endometrial preparation and
      timing.
AB  - STUDY QUESTION: What is the optimal endometrial preparation protocol for a frozen
      embryo transfer (FET)? SUMMARY ANSWER: Although the optimal endometrial
      preparation protocol for FET needs further research and is yet to be determined,
      we propose a standardized timing strategy based on the current available evidence
      which could assist in the harmonization and comparability of clinic practice and
      future trials. WHAT IS KNOWN ALREADY: Amid a continuous increase in the number of
      FET cycles, determining the optimal endometrial preparation protocol has become
      paramount to maximize ART success. In current daily practice, different FET
      preparation methods and timing strategies are used. STUDY DESIGN, SIZE, DURATION:
      This is a review of the current literature on FET preparation methods, with
      special attention to the timing of the embryo transfer. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Literature on the topic was retrieved in PubMed and references
      from relevant articles were investigated until June 2017. MAIN RESULTS AND THE
      ROLE OF CHANCE: The number of high quality randomized controlled trials (RCTs) is
      scarce and, hence, the evidence for the best protocol for FET is poor. Future
      research should compare both the pregnancy and neonatal outcomes between HRT and
      true natural cycle (NC) FET. In terms of embryo transfer timing, we propose to
      start progesterone intake on the theoretical day of oocyte retrieval in HRT and
      to perform blastocyst transfer at hCG + 7 or LH + 6 in modified or true NC,
      respectively. LIMITATIONS REASONS FOR CAUTION: As only a few high quality RCTs on
      the optimal preparation for FET are available in the existing literature, no
      definitive conclusion for benefit of one protocol over the other can be drawn so
      far. WIDER IMPLICATIONS OF THE FINDINGS: Caution when using HRT for FET is
      warranted since the rate of early pregnancy loss is alarmingly high in some
      reports. STUDY FUNDING/COMPETING INTEREST(S): S.M. is funded by the Research Fund
      of Flanders (FWO). H.T. and C.B. report grants from Merck, Goodlife, Besins and
      Abbott during the conduct of the study. TRIAL REGISTRATION NUMBER: Not
      applicable.

PMID- 29025057
TI  - NQO2 inhibition relieves reactive oxygen species effects on mouse oocyte meiotic
      maturation and embryo development.
AB  - NRH: quinone oxidoreductase 2 (NQO2) is a cytosolic and ubiquitously expressed
      flavoprotein that catalyzes the two-electron reduction of quinone to
      hydroquinones. Herein, we assessed the protein expression, subcellular
      localization, and possible functions of NQO2 in mouse oocyte meiotic maturation
      and embryo development. Western blot analysis detected high and stable protein
      expression of NQO2 in mouse oocytes during meiotic progression.
      Immunofluorescence illustrated NQO2 distribution on nuclear membrane,
      chromosomes, and meiotic spindles. Microtubule poisons treatment (nocodazole and
      taxol) showed that filamentous assembly of NQO2 and its co-localization with
      microtubules require microtubule integrity and normal dynamics. Increased levels
      of NQO2, reactive oxygen species (ROS), malondialdehyde (MDA), and autophagy
      protein Beclin1 expression were detected in oocytes cultured with ROS stimulator
      vitamin K3 (VK3), combined with decreased antioxidant glutathione (GSH). These
      oocytes were arrested at metaphase I with abnormal spindle structure and
      chromosome configuration. However, this impact was counteracted by melatonin or
      NQO2 inhibitor S29434, and the spindle configuration and first polar body
      extrusion were restored. Similarly, morpholino oligo-induced NQO2 knockdown
      suppressed ROS, MDA, and Beclin1, instead increased GSH in oocytes under VK3.
      Supplementary S29434 or melatonin limited changes in NQO2, ROS, MDA, Beclin1, and
      GSH during in vitro aging of ovulated oocytes, thereby maintaining spindle
      structure, as well as ordered chromosome separation and embryo development
      potential after parthenogenetic activation with SrCl2. Taken together, NQO2 is
      involved in ROS generation and subsequent cytotoxicity in oocytes, and its
      inhibition can restore oocyte maturation and embryo development, suggesting NQO2
      as a pharmacological target for infertility cure.

PMID- 29025059
TI  - Mindfulness for Chronic Low Back Pain: A Qualitative Analysis.
AB  - Objective: Mindfulness is a nonpharmacologic mind-body therapy that has been
      shown to be effective in older adults with chronic low back pain (cLBP). There
      are few first-person accounts in the literature that describe the older adult
      experience and perspective while learning mindfulness and meditation to treat
      pain. The objective of this study was to investigate dominant themes present in
      the experiences of older adults applying mindfulness and meditation to cope with
      cLBP. Design: Qualitative analysis of four focus groups. Subject: Twenty-five
      adults age 65 years or older who had completed an eight-week mindfulness program.
      Methods: The focus groups met for a comprehensive discussion session about their
      experience with mindfulness and meditation. The audio for each session was
      recorded, and the discussions were transcribed. Codebook development, qualitative
      coding, and thematic analysis were performed. The coders each coded all four
      transcripts, following which they met to adjudicate all coding differences until
      they were in complete agreement on coding. Results: Several key themes were
      brought up by older adults utilizing mindfulness as a means of coping with pain,
      which included overcoming fear of pain ("Before [learning mindfulness], I used to
      dread pain"), pain awareness ("You're focusing more on being aware than the pain;
      now that's what helps me"), and pain significance ("It becomes insignificant").
      Conclusions: The themes identify several ways mindfulness impacts older adults
      with cLBP, including decreased negative emotions related to chronic pain such as
      fear of pain, a different perspective or change in awareness about pain, and
      reducing the significance of pain.

PMID- 29025061
TI  - Nodular gastritis.

PMID- 29025058
TI  - Cohort Profile: Genetics of Diabetes Audit and Research in Tayside Scotland
      (GoDARTS).

PMID- 29025062
TI  - Deletion of Spata2 by CRISPR/Cas9n causes increased inhibin alpha expression and
      attenuated fertility in male mice.
AB  - As somatic cells in the testis seminiferous tubule, Sertoli cells provide the
      medium for spermatogenesis. One of the important functions of Sertoli cells is
      synthesizing and secreting cell factors to affect the production of sperm;
      however, much of those molecular regulation mechanisms remain unknown. Here, we
      confirm the localization of protein SPATA2 (spermatogenesis-associated protein
      2), which had previously been shown to be highly expressed in Sertoli cells of
      the adult mouse testis. To further conduct a functional study, we generated
      SPATA2 global knockout mice via use of the CRISPR/Cas9n gene editing technology.
      The 120-day-old knockout mice testes showed almost a 40% decrease in size and
      weight and variations in the histomorphology of the seminiferous epithelium, with
      a 40% decrease in sperm count. Further examination revealed that the
      proliferation of germ cells in the seminiferous tubules was attenuated by 28%. In
      addition, we found that SPATA2 deletion led to an approximately 70% increase in
      the inhibin alpha-subunit mRNA and protein level in the testes compared to that
      of wild-type mice. Our data revealed the impact of SPATA2 on male fertility and
      suggested that SPATA2 ensures the normal secretory function of Sertoli cells.

PMID- 29025063
TI  - Intelligence and all-cause mortality in the 6-Day Sample of the Scottish Mental
      Survey 1947 and their siblings: testing the contribution of family background.
AB  - Background: Higher early-life intelligence is associated with a reduced risk of
      mortality in adulthood, though this association is apparently hardly attenuated
      when accounting for early-life socio-economic status (SES). However, the use of
      proxy measures of SES means that residual confounding may underestimate this
      attenuation. In the present study, the potential confounding effect of early-life
      SES was instead accounted for by examining the intelligence-mortality association
      within families. Methods: The association between early-life intelligence and
      mortality in adulthood was assessed in 727 members of the 6-Day Sample of the
      Scottish Mental Survey 1947 and, for the first time, 1580 of their younger
      siblings. These individuals were born between 1936 and 1958, and were followed up
      into later life, with deaths recorded up to 2015. Cox regression was used to
      estimate the relative risk of mortality associated with higher IQ scores after
      adjusting for shared family factors. Results: A standard-deviation advantage in
      IQ score was associated with a significantly reduced mortality risk [hazard ratio
      = 0.76, p < 0.001, 95% confidence interval (CI) (0.68-0.84)]. This reduction in
      hazard was only slightly attenuated by adjusting for sex and shared family
      factors [hazard ratio = 0.79, p = 0.002, 95% CI (0.68-0.92)]. Conclusions:
      Although somewhat conservative, adjusting for all variance shared by a family
      avoids any potential residual confounding of the intelligence-mortality
      association arising from the use of proxy measures of early-life SES. The present
      study demonstrates that the longevity associated with higher early-life
      intelligence cannot be explained by early-life SES or within-family factors.

PMID- 29025060
TI  - Adrenomedullin improves fertility and promotes pinopodes and cell junctions in
      the peri-implantation endometrium.
AB  - Implantation is a complex event demanding contributions from both embryo and
      endometrium. Despite advances in assisted reproduction, endometrial receptivity
      defects persist as a barrier to successful implantation in women with
      infertility. We previously demonstrated that maternal haploinsufficiency for the
      endocrine peptide adrenomedullin (AM) in mice confers a subfertility phenotype
      characterized by defective uterine receptivity and sparse epithelial pinopode
      coverage. The strong link between AM and implantation suggested the compelling
      hypothesis that administration of AM prior to implantation may improve fertility,
      protect against pregnancy complications, and ultimately lead to better maternal
      and fetal outcomes. Here, we demonstrate that intrauterine delivery of AM prior
      to blastocyst transfer improves the embryo implantation rate and spacing within
      the uterus. We then use genetic decrease-of-function and pharmacologic gain-of
      function mouse models to identify potential mechanisms by which AM confers
      enhanced implantation success. In epithelium, we find that AM accelerates the
      kinetics of pinopode formation and water transport and that, in stroma, AM
      promotes connexin 43 expression, gap junction communication, and barrier
      integrity of the primary decidual zone. Ultimately, our findings advance our
      understanding of the contributions of AM to uterine receptivity and suggest
      potential broad use for AM as therapy to encourage healthy embryo implantation,
      for example, in combination with in vitro fertilization.

PMID- 29025065
TI  - 'Sleeping under the starry sky'-cysticercal encephalitis.

PMID- 29025064
TI  - Impact of adding hand-washing and water disinfection promotion to oral cholera
      vaccination on diarrhoea-associated hospitalization in Dhaka, Bangladesh:
      evidence from a cluster randomized control trial.
AB  - Background: Information on the impact of hygiene interventions on severe outcomes
      is limited. As a pre-specified secondary outcome of a cluster-randomized
      controlled trial among >400 000 low-income residents in Dhaka, Bangladesh, we
      examined the impact of cholera vaccination plus a behaviour change intervention
      on diarrhoea-associated hospitalization. Methods: Ninety neighbourhood clusters
      were randomly allocated into three areas: cholera-vaccine-only; vaccine-plus
      behaviour-change (promotion of hand-washing with soap plus drinking water
      chlorination); and control. Study follow-up continued for 2 years after
      intervention began. We calculated cluster-adjusted diarrhoea-associated
      hospitalization rates using data we collected from nearby hospitals, and 6
      monthly census data of all trial households. Results: A total of 429 995 people
      contributed 500 700 person-years of data (average follow-up 1.13 years). Vaccine
      coverage was 58% at the start of analysis but continued to drop due to population
      migration. In the vaccine-plus-behaviour-change area, water plus soap was present
      at 45% of hand-washing stations; 4% of households had detectable chlorine in
      stored drinking water. Hospitalization rates were similar across the study areas
      [events/1000 person-years, 95% confidence interval (CI), cholera-vaccine-only:
      9.4 (95% CI: 8.3-10.6); vaccine-plus-behaviour-change: 9.6 (95% CI: 8.3-11.1);
      control: 9.7 (95% CI: 8.3-11.6)]. Cholera cases accounted for 7% of total number
      of diarrhoea-associated hospitalizations. Conclusions: Neither cholera
      vaccination alone nor cholera vaccination combined with behaviour-change
      intervention efforts measurably reduced diarrhoea-associated hospitalization in
      this highly mobile population, during a time when cholera accounted for a small
      fraction of diarrhoea episodes. Affordable community-level interventions that
      prevent infection from multiple pathogens by reliably separating faeces from the
      environment, food and water, with minimal behavioural demands on impoverished
      communities, remain an important area for research.

PMID- 29025066
TI  - Supply and demand: application of Lean Six Sigma methods to improve drug round
      efficiency and release nursing time.
AB  - Objective: To improve efficiency, reduce interruptions and reduce the time taken
      to complete oral drug rounds. Design: Lean Six Sigma methods were applied to
      improve drug round efficiency using a pre- and post-intervention design. Setting:
      A 20-bed orthopaedic ward in a large teaching hospital in Ireland. Participants:
      Pharmacy, nursing and quality improvement staff. Intervention(s): A multifaceted
      intervention was designed which included changes in processes related to drug
      trolley organization and drug supply planning. A communications campaign aimed at
      reducing interruptions during nurse-led during rounds was also developed and
      implemented. Main outcome measure(s): Average number of interruptions, average
      drug round time and variation in time taken to complete drug round. Results: At
      baseline, the oral drug round took an average of 125 min. Following application
      of Lean Six Sigma methods, the average drug round time decreased by 51 min. The
      average number of interruptions per drug round reduced from an average of 12 at
      baseline to 11 following intervention, with a 75% reduction in drug supply
      interruptions. Conclusions: Lean Six Sigma methodology was successfully employed
      to reduce interruptions and to reduce time taken to complete the oral drug round.

PMID- 29025067
TI  - Commentary: Pancreatic cancer: is the worst to come?

PMID- 29025068
TI  - Dry ice (solid carbon dioxide) exposure with disastrous consequences.

PMID- 29025070
TI  - Interdisciplinary Family Conferences to Improve Patient Experience in the
      Neonatal Intensive Care Unit.
AB  - Parents play a significant role in the development of their neonate. They can
      affect the length of stay in a neonatal intensive care unit (NICU) and are seen
      as an integral part of the team. Parents are often put in positions where
      difficult decision making is required of them in the care of their critically ill
      child. Studies suggest that one way to improve the family's experience and to
      encourage their involvement is by establishing a formal and focused family
      conference. Therefore, the NICU social workers and the interdisciplinary team
      collaborated to formulate strategies to improve communication that would enhance
      current practice. As a new initiative, the team decided that holding an
      interdisciplinary family conference (IFC) within the first two weeks of a baby's
      NICU admission is critical for parental involvement of infants less than 32 weeks
      gestation and those with congenital birth anomalies. The team determined that the
      primary outcome measure would be family satisfaction scores from hospital
      surveys. Since the implementation of IFCs, satisfaction scores showed steady
      improvement. This quality improvement project demonstrated that IFCs are an
      integral part of the family-centered care approach in the NICU. IFCs foster
      partnerships with families to ensure their involvement in all aspects of patient
      care and improve their experience in the NICU.

PMID- 29025071
TI  - The expression characteristics of FAM71D and its association with sperm motility.
AB  - STUDY QUESTION: What are the features of FAM71D (Family with sequence similarity
      71, member D) expression and is there an association between FAM71D expression
      and sperm motility? SUMMARY ANSWER: FAM71D, a novel protein exclusively expressed
      in the testis, is located in sperm flagella and is functionally involved in sperm
      motility. WHAT IS KNOWN ALREADY: Some testis-specific proteins have been reported
      as potential diagnostic biomarkers to evaluate the spermatogenesis process and
      sperm quality. We have identified a novel testis-specific protein, FAM71D,
      through microarray data analysis, yet little is known about its expression and
      function. STUDY DESIGN, SIZE, DURATION: FAM71D mRNA and protein expression was
      quantified during mouse testis development. Its localization in germ cells was
      detected by dual-labeled immunostaining in testis sections and sperm smears. The
      clinical significance was assessed by comparing FAM71D expression in spermatozoa
      from normozoospermic controls and asthenozoospermic patients.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Testes were dissected from C57BL/6 J
      male mice at postnatal ages of 1, 2, 3, 4, 6, 8 weeks and 6 months, and sperm was
      collected from cauda epididymides of adult mice by the swim-up method. Human
      spermatozoa were isolated from 100 human semen samples by density gradient
      Percoll centrifugation. RT-qPCR and western blot were performed to semi-quantify
      the expression of FAM71D in mouse testis, and in the ejaculated spermatozoa of
      normozoospermic controls and asthenozoospermic patients. Immunofluorescence
      staining was used to detect the localization of FAM71D. Co-immunoprecipitation
      assay was performed to evaluate the interaction between FAM71D and calmodulin. An
      antibody blocking assay was employed to assess the role of FAM71D in sperm
      motility. MAIN RESULTS AND THE ROLE OF CHANCE: Our results showed that FAM71D was
      exclusively expressed in the testis in an age-dependent manner. FAM71D expression
      exhibited dynamic change in the cytoplasm of spermatids during spermiogenesis and
      was finally retained in sperm flagella. FAM71D could interact with calmodulin.
      Use of anti-FAM71D antibody on sperm significantly decreased sperm motility.
      Expression level of FAM71D was markedly reduced in the ejaculated spermataozoa of
      asthenozoospermic patients (P < 0.05), and this was correlated with sperm
      progressive motility (r = 0.7435, P < 0.0001). LARGE SCALE DATA: N/A.
      LIMITATIONS, REASONS FOR CAUTION: The sample size was limited and it is necessary
      to verify the correlation of FAM71D expression with sperm motility in larger
      cohorts. Furthermore, our results were descriptive and follow-up studies would be
      needed to elucidate the detailed role of FAM71D in sperm motility. WIDER
      IMPLICATIONS OF THE FINDINGS: This is the first systematic study to document the
      expression of endogenous FAM71D and a function for FAM71D in sperm motility. It
      provides new insights into our understanding of sperm motility regulation and
      causes of male infertility. STUDY FUNDING/COMPETING INTERESTS: This study was
      funded by the National Natural Science Foundation of China, Guangdong Natural
      Science Foundation and the Shenzhen Project of Science and Technology. The
      authors have no competing interests.

PMID- 29025069
TI  - WNK lysine deficient protein kinase 1 regulates human endometrial stromal cell
      decidualization, proliferation, and migration in part through mitogen-activated
      protein kinase 7.
AB  - The differentiation of endometrial stromal cells into decidual cells, termed
      decidualization, is an integral step in the establishment of pregnancy. The
      mitogen-activated protein kinase homolog, WNK lysine deficient protein kinase 1
      (WNK1), is activated downstream of epidermal growth factor receptor during
      decidualization. Primary human endometrial stromal cells (HESCs) were subjected
      to small interfering RNA knockdown of WNK1 followed by in vitro decidualization.
      This abrogated expression of the decidual marker genes, insulin like growth
      factor binding protein 1 (IGFBP1) and prolactin (PRL), and prevented adoption of
      decidual cell morphology. Analysis of the WNK1-dependent transcriptome by RNA-Seq
      demonstrated that WNK1 regulates the expression of 1858 genes during
      decidualization. Gene ontology and upstream regulator pathway analysis showed
      that WNK1 regulates cell migration, differentiation, and proliferation. WNK1 was
      required for many of the gene expression changes that drive decidualization,
      including the induction of the inflammatory cytokines, C-C motif chemokine ligand
      8 (CCL8), interleukin 1 beta (IL1B), and interleukin 15 (IL15), and the
      repression of transforming growth factor-beta (TGF-beta) pathway genes, including
      early growth response 2 (EGR2), SMAD family member 3 (SMAD3), integrin subunit
      alpha 2 (ITGA2), integrin subunit alpha 4 (ITGA4), and integrin subunit beta 3
      (ITGB3). In addition to abrogating decidualization, WNK1 knockdown decreased the
      migration and proliferation of HESCs. Furthermore, mitogen-activated protein
      kinase 7 (MAPK7), a known downstream target of WNK1, was activated during
      decidualization in a WNK1-dependent manner. Small interfering RNA knockdown of
      MAPK7 demonstrated that MAPK7 regulates a subset of WNK1-regulated genes and
      controls the migration and proliferation of HESCs. These results indicate that
      WNK1 and MAPK7 promote migration and proliferation during decidualization and
      regulate the expression of inflammatory cytokines and TGF-beta pathway genes in
      HESCs.

PMID- 29025073
TI  - Cohort Profile: The FinnBrain Birth Cohort Study (FinnBrain).

PMID- 29025072
TI  - Declining exposures to lead and cadmium contribute to explaining the reduction of
      cardiovascular mortality in the US population, 1988-2004.
AB  - Background: Lead and cadmium exposures have markedly declined in the USA
      following the implementation of large-scale public health policies and could have
      contributed to the unexplained decline in cardiovascular mortality in US adults.
      We evaluated the potential contribution of lead and cadmium exposure reductions
      to explain decreasing cardiovascular mortality trends occurring in the USA from
      1988-94 to 1999-2004. Methods: Prospective study in 15 421 adults >=40 years old
      who had participated in the National Health and Nutrition Examination Survey 1988
      94 or 1999-2004. We estimated the amount of change in cardiovascular mortality
      over time that can be independently attributed to the intermediate pathway of
      changes in blood lead and urine cadmium concentrations. Results: There was a
      42.0% decrease in blood lead and a 31.0% decrease in urine cadmium
      concentrations. The cardiovascular mortality rate ratio [95% confidence intervals
      (CIs)] associated with a doubling of metal levels was 1.19 (1.07, 1.31) for blood
      lead and 1.20 (1.09, 1.32) for urine cadmium. The absolute reduction in
      cardiovascular deaths comparing 1999-2004 to 1988-94 was 230.7 deaths/100 000
      person-years, in models adjusted for traditional cardiovascular risk factors.
      Among these avoided deaths, 52.0 (95% CI 8.4, 96.7) and 19.4 (4.3, 36.4)
      deaths/100 000 person-years were attributable to changes in lead and cadmium,
      respectively. Conclusions: Environmental declines in lead and cadmium exposures
      were associated with reductions in cardiovascular mortality in US adults. Given
      the fact that lead and cadmium remain associated with cardiovascular disease at
      relatively low levels of exposure, prevention strategies that further minimize
      exposure to lead and cadmium may be needed.

PMID- 29025074
TI  - The impact of centralization of services on treatment delay in ovarian cancer: A
      study on process quality.
AB  - Objective: Emphasis on improving healthcare quality has led to centralization of
      services for patients suspected of ovarian cancer. As centralization of services
      may induce treatment delays, we aimed to assess compliance with health system
      interval guidelines in patients suspected of ovarian cancer. Design: Evaluation
      of health system intervals, comparison between direct and indirect referrals and
      between 2013 and 2014. Setting: A managed clinical network (MCN) comprising 11
      hospitals in the Netherlands. Participants: Patients that were treated for
      ovarian cancer within the University Medical Center Groningen in 2013 and 2014.
      Intervention: Introduction of an MCN to centralize services for patients
      suspected of ovarian cancer. Main Outcome Measure: Compliance with national
      guidelines regarding health system intervals. Results: Between 2013 and 2014 a
      clinically relevant improvement in compliance with guidelines was demonstrated.
      Within this period, median treatment intervals decreased from 34 to 29 days, and
      the percentage of patients in which treatment interval guidelines were met
      increased from 63.5 to 72.2%. New regulations and increased awareness of health
      system intervals inspired changes in local practice leading to improved
      compliance with guidelines. Compliance was highest in patients that were directly
      referred to our academic hospital. Conclusion: Evaluation of health system
      intervals in patients suspected of ovarian cancer was feasible and may be
      applicable to other MCNs. Though compliance with guidelines improved within the
      study period, there is potential for improvement. To facilitate real-time
      evaluation of compliance with national guidelines establishing uniformity of
      electronic patient files in the MCN is deemed essential.

PMID- 29025075
TI  - Possible Association between Serum Matrix Metalloproteinase-9 (MMP-9) Levels and
      Relapse in Depressed Patients following Electroconvulsive Therapy (ECT).
AB  - Background: Matrix metalloproteinases are involved in neuroinflammatory
      processes, which could underlie depression. Serum levels of MMP-9 and MMP-2 in
      depressed patients are significantly altered following electroconvulsive therapy,
      but an association between altered matrix metalloproteinases after successful ECT
      and possible relapse has yet to be investigated. Methods: Serum was obtained
      twice, before and immediately after a course of electroconvulsive therapy, from
      38 depressed patients. Serum was also collected, once, from two groups of age-
      and gender-matched healthy controls, 40 volunteers in each group. Possible
      associations between levels of matrix metalloproteinases and relapse during a 1
      year follow-up period were analyzed. Results: Excluding patients who did not
      respond to electroconvulsive therapy and patients lost to follow-up, data from 28
      patients were evaluated. Eighteen of the patients (64.3%) relapsed within 1 year.
      In the group that did not relapse, serum levels of MMP-9 were significantly
      decreased after a course of electroconvulsive therapy, but not in the group that
      relapsed. No association between MMP-2 and relapse was observed. Conclusion: The
      degree of change in serum MMP-9 change could be associated with relapse following
      electroconvulsive therapy in depressed patients.

PMID- 29025077
TI  - Impact of Fasting on Complete Blood Count Assayed in Capillary Blood Samples.
AB  - Background: To determine the effect of food intake on complete blood count (CBC)
      results. Method: We analyzed the CBC in whole capillary blood specimens collected
      from 33 adult volunteers into microtubes between 8:00 AM and 11:00 AM. Blood
      specimens were drawn from patients who had been fasting 12 hours and then 1 and 2
      hours after consumption of a light meal containing carbohydrates, protein, and
      lipids. All measurements were performed using the hematologic analyzer Sysmex XN
      1000. Results: The red blood cell count, hemoglobin concentration, hematocrit
      level, and platelet count decreased 2 hours after meal consumption (P = .007, P =
      .008, P = .003, and P = .03, respectively). The lymphocyte number decreased after
      the first and second hour following meal consumption (P = .004 and P = .001); the
      number of neutrophils had increased 1 and 2 hours after food intake (P = .003 and
      P = .006, respectively). Conclusions: Food consumption impacts CBC results. To
      ensure the consistency, quality, and repeatability of CBC analysis, blood should
      be drawn from fasting patients.

PMID- 29025076
TI  - Impact of smoking, alcohol consumption, and NSAID use on risk for and phenotypes
      of eosinophilic esophagitis.
AB  - There are few data exploring modifiable risk factors for eosinophilic esophagitis
      (EoE). We aimed to determine if smoking, alcohol consumption, and nonsteroidal
      anti-inflammatory drug (NSAID) use were risk factors for EoE, and to assess their
      impact on EoE phenotypes and treatment outcomes. We performed a case-control
      study analyzing data collected from a prospective cohort of adults undergoing
      upper endoscopy for symptoms of esophageal dysfunction. Incident EoE cases were
      diagnosed via consensus guidelines. Exposure data were collected via standardized
      patient questionnaire. Follow-up assessments for cases were made after treatment,
      with histologic response defined as <15 eosinophils per high-power field
      (eos/hpf). Exposures were compared between EoE cases and controls, among EoE
      cases with and without fibrostenosis, and among EoE responders and nonresponders.
      A total of 115 cases and 225 controls were analyzed. Cases were less likely to
      have ever smoked cigarettes (23% vs. 47%, P < 0.001) or currently use NSAIDs (17%
      vs. 40%, P < 0.001) compared to controls. These relations persisted after
      multivariate analysis. Although alcohol use was more common among cases (75% vs.
      51%, P < 0.001), the effect was abrogated after multivariate analysis. Smoking,
      alcohol, and NSAID use were not associated with the fibrostenotic phenotype.
      There was a trend toward improved histologic response among EoE patients
      concomitantly using NSAIDs (87% vs. 63%, P = 0.08; aOR 6.97 (95% CI: 0.81-60.3).
      In conclusion, NSAID and smoking were inversely associated with EoE compared to
      endoscopy-based controls. Alcohol use was more prevalent in the EoE cases,
      although not an independent risk factor. Concomitant NSAID use may improve
      treatment response and is worthy of future study.

PMID- 29025078
TI  - A cloud on the horizon-a survey into the use of electronic vaping devices for
      recreational drug and new psychoactive substance (NPS) administration.
AB  - Background: There is limited published scientific data on vaping recreational
      drugs other than cannabis. A recent review suggested that 15% of people vaping
      cannabis have also vaped a synthetic cannabinoid receptor agonist (SCRA) and
      identified over 300 Internet reports of e-liquid manufacture of recreational
      drugs and/or new psychoactive substances (NPS). Aim: To determine the prevalence
      of use of electronic vaping devices for recreational drug and NPS delivery in the
      UK. Design: A voluntary online survey using a convenience sample of UK adult
      participants (aged 16 years old and over) identified by a market research
      company. Methods: Data was collected regarding demographics, smoking history,
      electronic vaping device history and recreational drug/NPS use and route of
      administration. Results: There were 2501 respondents. The mean (+/-SD) age was
      46.2 +/- 16.8 years old. The commonest lifetime recreational drug used was
      Cannabis (818, 32.7%). The majority of respondents had smoked (1545, 61.8%) with
      731 (29.2%) being current smokers. The most commonly used SCRA product was 'Spice
      Gold' (173, 6.9%) and SCRA compound was ADB-CHMICA (48, 1.9%). 861 (34.4%) had
      used an electronic vaping device; 340 (13.6%) having used them for recreational
      drug administration; 236 (9.4%) reporting current use. The commonest lifetime
      recreational drug to be vaped was cannabis (155, 65.7%), with electronic
      cigarettes (230, 48.2%) being the commonest reported route of SCRA compound
      administration. Conclusion: 9.4% of respondents currently use electronic vaping
      devices for recreational drug administration with 6.2% reporting lifetime
      cannabis vaping use. Further larger scale studies are required to help inform the
      appropriate treatment and primary prevention strategies.

PMID- 29025079
TI  - Transcriptome profiling of individual rhesus macaque oocytes and preimplantation
      embryos.
AB  - Early mammalian embryonic transcriptomes are dynamic throughout the process of
      preimplantation development. Cataloging of primate transcriptomics during early
      development has been accomplished in humans, but global characterization of
      transcripts is lacking in the rhesus macaque: a key model for human reproductive
      processes. We report here the systematic classification of individual macaque
      transcriptomes using RNA-Seq technology from the germinal vesicle stage oocyte
      through the blastocyst stage embryo. Major differences in gene expression were
      found between sequential stages, with the 4- to 8-cell stages showing the highest
      level of differential gene expression. Analysis of putative transcription factor
      binding sites also revealed a striking increase in key regulatory factors in 8
      cell embryos, indicating a strong likelihood of embryonic genome activation
      occurring at this stage. Furthermore, clustering analyses of gene co-expression
      throughout this period resulted in distinct groups of transcripts significantly
      associated to the different embryo stages assayed. The sequence data provided
      here along with characterizations of major regulatory transcript groups present a
      comprehensive atlas of polyadenylated transcripts that serves as a useful
      resource for comparative studies of preimplantation development in humans and
      other species.

PMID- 29025081
TI  - The long-term effects of early oral feeding following minimal invasive
      esophagectomy.
AB  - A nil-by-mouth regime with enteral nutrition via an artificial route is
      frequently applied following esophagectomy. However, early initiation of oral
      feeding could potentially improve recovery and has shown to be beneficial in many
      types of abdominal surgery. Although short-term nutritional safety of oral intake
      after an esophagectomy has been documented, long-term effects of this feeding
      regimen are unknown. In this cohort study, data from patients undergoing minimal
      invasive Ivor-Lewis esophagectomy between 04-2012 and 09-2015 in three centers in
      Netherlands were collected. Patients in the oral feeding group were retrieved
      from a previous prospective study and compared with a cohort of patients with
      early enteral jejunostomy feeding but delayed oral intake. Body mass index (BMI)
      measurements, complications, and nutritional re-interventions (re- or start of
      artificial feeding, start of total parenteral nutrition) were gathered over the
      course of one year after surgery. One year after surgery the median BMI was 22.8
      kg/m2 and weight loss was 7.0 kg (9.5%) in 114 patients. Patients in the early
      oral feeding group lost more weight during the first postoperative month (P =
      0.004). However, in the months thereafter this difference was not observed
      anymore. In the early oral feeding group, 28 patients (56%) required a
      nutritional re-intervention, compared to 46 patients (72%) in the delayed oral
      feeding group (P = 0.078). During admission, more re-interventions were performed
      in the delayed oral feeding group (17 vs. 46 patients P < 0.001). Esophagectomy
      reduces BMI in the first year after surgery regardless of the feeding regimen.
      Direct start of oral intake following esophagectomy has no impact on early
      nutritional re-interventions and long-term weight loss.

PMID- 29025082
TI  - Intestinal absorption of vitamin D: a systematic review.
AB  - Context: Vitamin D is frequently prescribed as a supplement, yet its absorption
      remains poorly understood. Objective: This systematic review was performed to
      evaluate data on mechanisms involved in the intestinal absorption of vitamin D.
      Data Sources: PubMed, Embase, and Cochrane Library databases were searched. Study
      Selection: The following studies were included: experimental laboratory studies
      of vitamin D absorption through the enterocyte brush-border membrane; absorption
      tests that used radiolabeled vitamin D; and clinical trials in adults that
      investigated a single dose of cholecalciferol or ergocalciferol and reported at
      least 2 measurements of serum cholecalciferol, ergocalciferol, or 25
      hydroxyvitamin D. Data Extraction: From 2069 articles identified, 46 met the
      inclusion criteria. Results: Different methods were employed to evaluate vitamin
      D absorption. Recent research suggests that vitamin D absorption is not an
      exclusive simple diffusion process. Vitamin D was better absorbed when it was
      consumed with fat-containing meals, but absorption also occurred without fat or
      oily vehicles. Factors that modified cholesterol absorption also altered vitamin
      D absorption. Conclusion: Vitamin D is probably absorbed through passive
      diffusion and a mechanism involving membrane carriers, especially cholesterol
      transporters, although data remain scarce. Some data suggest that fat, when
      consumed concomitantly with vitamin D, improves vitamin D absorption.

PMID- 29025080
TI  - Exposure to perchlorate, nitrate and thiocyanate, and prevalence of diabetes
      mellitus.
AB  - Background: It is known that perchlorate, nitrate and thiocyanate have the
      property of inhibiting sodium iodide symporter. Animal studies have suggested
      that these compounds, especially perchlorate, might also interfere with insulin
      secretion. However, the association between their exposure and diabetes risk is
      largely unknown in humans. Methods: Among 11 443 participants (mean age 42.3
      years) from the National Health and Nutritional Examination Survey 2001-14,
      urinary perchlorate, nitrate and thiocyanate were measured by using ion
      chromatography coupled with electrospray tandem mass spectrometry. Diabetes was
      defined as self-reported doctor diagnosis, use of oral hypoglycaemic medication
      or insulin, fasting plasma glucose >= 126 mg/dl or glycated haemoglobin A1c
      (HbA1c) >= 6.5%. Results: The median (interquartile range) levels of urinary
      perchlorate, nitrate and thiocyanate were 3.32 (1.84, 5.70) MUg/l, 46.4 (27.9,
      72.0) mg/l and 1.23 (0.59, 2.78) mg/l, respectively. Higher levels of urinary
      perchlorate were associated with elevated levels of fasting glucose, HbA1c,
      insulin and homeostatic model assessment of insulin resistance (all Ptrend <
      0.001). After multivariate adjustment including urinary creatinine, smoking
      status and body mass index (BMI), higher urinary perchlorate, but not nitrate or
      thiocyanate, was associated with an increased prevalence of diabetes mellitus.
      Comparing extreme quintiles, the odds ratio (95% confidence interval) of diabetes
      was 1.53 (1.21, 1.93; Ptrend < 0.001) for perchlorate, 1.01 (0.77, 1.32; Ptrend =
      0.44) for nitrate and 0.98 (0.73, 1.31; Ptrend = 0.64) for thiocyanate. When
      urinary perchlorate, nitrate and thiocyanate were further mutually adjusted, the
      results did not materially change. Similar results were observed when analyses
      were stratified by smoking status, as well as by age, gender, kidney function and
      BMI. Conclusions: Higher urinary perchlorate levels are associated with an
      increased prevalence of diabetes mellitus, independent of traditional risk
      factors. Future prospective studies are needed to confirm these findings.

PMID- 29025083
TI  - The duration of protection of school-aged BCG vaccination in England: a
      population-based case-control study.
AB  - Background: Evidence of protection from childhood Bacillus Calmette-Guerin (BCG)
      against tuberculosis (TB) in adulthood, when most transmission occurs, is
      important for TB control and resource allocation. Methods: We conducted a
      population-based case-control study of protection by BCG given to children aged
      12-13 years against tuberculosis occurring 10-29 years later. We recruited UK
      born White subjects with tuberculosis and randomly sampled White community
      controls. Hazard ratios and 95% confidence intervals (CIs) were estimated using
      case-cohort Cox regression, adjusting for potential confounding factors,
      including socio-economic status, smoking, drug use, prison and homelessness.
      Vaccine effectiveness (VE = 1 - hazard ratio) was assessed at successive
      intervals more than 10 years following vaccination. Results: We obtained 677
      cases and 1170 controls after a 65% response rate in both groups. Confounding by
      deprivation, education and lifestyle factors was slight 10-20 years after
      vaccination, and more evident after 20 years. VE 10-15 years after vaccination
      was 51% (95% CI 21, 69%) and 57% (CI 33, 72%) at 15-20 years. Subsequently, BCG
      protection appeared to wane; 20-25 years VE = 25% (CI -14%, 51%) and 25-29 years
      VE = 1% (CI -84%, 47%). Based on multiple imputation of missing data (in 17%
      subjects), VE estimated in the same intervals after vaccination were similar [56%
      (CI 33, 72%), 57% (CI 36, 71%), 25% (-10, 48%), 21% (-39, 55%)]. Conclusions:
      School-aged BCG vaccination offered moderate protection against tuberculosis for
      at least 20 years, which is longer than previously thought. This has implications
      for assessing the cost-effectiveness of BCG vaccination and when evaluating new
      TB vaccines.

PMID- 29025084
TI  - Association between adult height, myocardial infarction, heart failure, stroke
      and death: a Korean nationwide population-based study.
AB  - Background: The association between adult height and cardiovascular (CV) events
      and mortality has been suggested, albeit inconsistently. We sought to discover
      the comprehensive relationship between height, CV-related morbidity and all-cause
      death according to age. Methods: We investigated the association between adult
      height and myocardial infarction (MI), heart failure (HF), stroke incidence and
      mortality in 16 528 128 Korean patients who underwent regular health check-ups
      (2005-08). Height was stratified by decile according to age (20-39 years, 40-59
      years and >=60 years) and gender. Results: During a 9-year follow-up period, 590
      346 participants died and 232 093 were admitted to hospital for MI, 201 411 for
      HF and 267 566 for stroke. An inverse relationship between height and MI, HF,
      stroke and all-cause death was observed in the overall cohort analysis. The
      association was unchanged after adjusting for CV risk and behavioural and
      adulthood socioeconomic factors. Both male and female sex showed an inverse
      relationship with height in adulthood, CV events and mortality. Adult height
      showed an inverse association in all CV events and mortality, especially in the
      older groups (>=40 years). In a subgroup analysis of body mass index, there was
      an inverse relationship between height, CV events and mortality in each group.
      Conclusions: Shorter height in adulthood was strongly related to an increased
      risk of MI, HF, stroke and all-cause death. A suitable environment and
      appropriate nutrition early in life could influence adult height and eventually
      reduce the risk of CV events and mortality.

PMID- 29025085
TI  - Effects of Buprenorphine on Responses to Emotional Stimuli in Individuals with a
      Range of Mood Symptomatology.
AB  - Background: The opioid drug buprenorphine has been shown to modify responses to
      emotional stimuli and may have antidepressant properties. In preclinical studies,
      it shows antidepressant-like and anxiolytic-like effects, and a handful of
      clinical studies suggest it may reduce symptoms of depression in patients. We
      have shown that low doses of buprenorphine reduce responses to negative emotional
      stimuli in healthy adults. Here we extended these findings to individuals with
      symptoms of depression and anxiety. Methods: We examined the effects of
      buprenorphine on attention to emotional facial expressions and ratings of and
      psychophysiological responses to emotional images in adults with a range of mood
      symptomatology. Volunteers (n=38) were recruited with low, mild, moderate, and
      severe scores on the Depression-Anxiety-Stress Scale. They attended 2 laboratory
      sessions during which they received either placebo or 0.2 mg sublingual
      buprenorphine in randomized order under double-blind conditions. During peak drug
      effect, participants completed a visual attention task assessing responses to
      emotional faces and a picture-rating task assessing responses to emotional images
      with and without social content. Results: Buprenorphine reduced attention to
      fearful facial expressions as it did in our previous study, and the emotion
      specific effect was especially pronounced in individuals with high Depression
      Anxiety-Stress Scale scores. The drug also increased ratings of positivity of
      images with social content, but this effect was less strong in individuals with
      higher Depression-Anxiety-Stress Scale scores. Conclusions: These results suggest
      low doses of buprenorphine may reduce some dimensions of responses to negative
      emotional stimuli in individuals high on depression or anxiety, while leaving
      other dimensions unaffected.

PMID- 29025086
TI  - A critical appraisal of guidelines for electronic communication between patients
      and clinicians: the need to modernize current recommendations.
AB  - Background: Patient-provider electronic communication has proliferated in recent
      years, yet there is a dearth of published research either leading to, or
      including, recommendations that improve clinical care and prevent unintended
      negative consequences. We critically appraise published guidelines and suggest an
      agenda for future work in this area. Objective: To understand how existing
      guidelines align with current practice, evidence, and technology. Methods: We
      performed a narrative review of provider-targeted guidelines for electronic
      communication between patients and providers, searching Ovid MEDLINE, Embase, and
      PubMed databases using relevant terms. We limited the search to articles
      published in English, and manually searched the citations of relevant articles.
      For each article, we identified and evaluated the suggested practices. Results:
      Across 11 identified guidelines, the primary focus was on technical and
      administrative concerns, rather than on relational communication. Some of the
      security practices recommended by the guidelines are no longer needed because of
      shifts in technology. It is unclear the extent to which the recommendations that
      are still relevant are being followed. Moreover, there is no guideline-cited
      evidence of the effectiveness of the practices that have been proposed.
      Conclusion: Our analysis revealed major weaknesses in current guidelines for
      electronic communication between patients and providers: the guidelines appear to
      be based on minimal evidence and offer little guidance on how best to use
      electronic tools to communicate effectively. Further work is needed to
      systematically evaluate and identify effective practices, create a framework to
      evaluate quality of communication, and assess the relationship between electronic
      communication and quality of care.

PMID- 29025087
TI  - Field Measurements of Inadvertent Ingestion Exposure to Metals.
AB  - The determinants of inadvertent occupational ingestion exposure are poorly
      understood, largely due to a lack of available exposure measurement data. In this
      study, perioral exposure wipes were used as a surrogate for inadvertent ingestion
      exposure to measure exposure to eight metals (chromium, nickel, aluminium,
      cobalt, lead, arsenic, manganese, and tin) among 38 workers at 5 work sites in
      the UK. This work was done alongside a previously reported observational study of
      hand/object-to-mouth contact frequency. Systematic wipes of the perioral area,
      and of both hands were taken with proprietary cellulose wipes pre-moistened with
      deionized water. Measurements were taken at the beginning, middle and end of the
      shift. Mixed-effect models of exposure measurements were built with area of skin
      sampled, time during shift, and job group entered as fixed effects and worker
      identification as a random effect. Linear regression modelling was used to study
      the effect of hand/object-to-mouth contact frequency on perioral exposure,
      adjusting for the measured exposure on the hand and observed respirator use. Hand
      and perioral exposure measurements were correlated with one another (r = 0.79)
      but mass per unit area exposure was significantly higher on the perioral area
      than on the hands for seven of the metals (at P < 0.05). There were no
      significant differences between measurements taken at the middle or the end of
      the shift for five of the metals suggesting that dermal loading may remain
      relatively constant for much of the workday. This applies to both hand and
      perioral measurements. In linear regression modelling there was no relationship
      between hand/object-to-mouth contact frequency and perioral exposure, but hand
      exposure was significantly positively related to perioral exposure and workers
      who used respirators had significantly higher perioral exposure than those who
      did not. The results suggest the levels of exposure on the hand and respirator
      use are important determinants of potential inadvertent ingestion exposure. The
      results did not demonstrate a relationship between perioral exposure and hand-to
      mouth contact frequency. Perioral wipe sampling may be a useful surrogate measure
      for exposure by the inadvertent ingestion route, but further research is required
      to confirm the link between perioral levels and actual exposure, measured using
      biological monitoring.

PMID- 29025089
TI  - Oral Ketamine for Acute Pain Management After Amputation Surgery.
AB  - Objective: Intravenous ketamine has been shown to provide postoperative analgesia
      in many clinical trials, in particular to reduce opioid consumption. The primary
      objective of this pilot study is to determine if multiple dosing over a three-day
      perioperative period with oral ketamine is a safe treatment method for acute pain
      after amputation surgery. Methods: Three consented subjects (age 57-60 years)
      undergoing elective amputation of the lower extremity were included in the study
      (Institutional Review Board and Food and Drug Administration Investigational New
      Drug approved). An analgesic dose of oral ketamine (1.0 mg/kg) was administered
      one hour before surgery. Eight hours after the preoperative dose, a second dose
      was given. On the first postoperative day, subjects received oral ketamine (1.0
      mg/kg) three times per day; and on the second postoperative day, this dose was
      reduced to 0.5 mg/kg three times per day. The primary outcome measure was the
      incidence of adverse events. Results: No serious and unexpected adverse events
      occurred; therefore, no subject required a dose reduction. The numerical rating
      score for postoperative pain of the body part adjacent to the amputation site
      ranged from 0.5-4.0. Morphine milligram equivalent opioid doses were in the range
      of 0-17.5 mg on the first postop day and 1.0-4.0 mg on the second postop day.
      Conclusions: Our pilot study suggests that oral ketamine is safe to use at 1
      mg/kg three times per day, as well as convenient for hospital floor and potential
      home use. Future studies will determine if the perioperative oral ketamine also
      reduces the incidence of chronic stump or phantom limb pain.

PMID- 29025088
TI  - Cohort Profile: The Siyakhula Cohort, rural South Africa.

PMID- 29025090
TI  - Effect of number of open charts on intercepted wrong-patient medication orders in
      an emergency department.
AB  - To reduce the risk of wrong-patient errors, safety experts recommend allowing
      only one patient chart to be open at a time. Due to the lack of empirical
      evidence, the number of allowable open charts is often based on anecdotal
      evidence or institutional preference, and hence varies across institutions. Using
      an interrupted time series analysis of intercepted wrong-patient medication
      orders in an emergency department during 2010-2016 (83.6 intercepted wrong
      patient events per 100 000 orders), we found no significant decrease in the
      number of intercepted wrong-patient medication orders during the transition from
      a maximum of 4 open charts to a maximum of 2 (b = -0.19, P = .33) and no
      significant increase during the transition from a maximum of 2 open charts to a
      maximum of 4 (b = 0.08, P = .67). These results have implications regarding
      decisions about allowable open charts in the emergency department in relation to
      the impact on workflow and efficiency.

PMID- 29025091
TI  - Commentary: A pancreatic cancer incidence and mortality gap?

PMID- 29025092
TI  - Heat stress induces autophagy in pig ovaries during follicular development.
AB  - Hyperthermia or heat stress (HS) occurs when heat dissipation mechanisms are
      overwhelmed by external and internal heat production. Hyperthermia negatively
      affects reproduction and potentially compromises oocyte integrity and reduces
      developmental competence of ensuing embryos. Autophagy is the process by which
      cells recycle energy through the reutilization of cellular components and is
      activated by a variety of stressors. Study objectives were to characterize
      autophagy-related proteins in the ovary following cyclical HS during the
      follicular phase. Twelve gilts were synchronized and subjected to cyclical HS (n
      = 6) or thermal neutral (n = 6) conditions for 5 days during the follicular
      phase. Ovarian protein abundance of Beclin 1 and microtubule associated protein
      light chain 3 beta II were each elevated as a result of HS (P = 0.001 and 0.003,
      respectively). The abundance of the autophagy related (ATG)12-ATG5 complex was
      decreased as a result of HS (P = 0.002). Regulation of autophagy and apoptosis
      occurs in tight coordination, and B-cell lymphoma (BCL)2 and BCL2L1 are involved
      in regulating both processes. BCL2L1 protein abundance, as detected via
      immunofluorescence, was increased in both the oocyte (~1.6-fold; P < 0.01) and
      granulosa cells of primary follicles (~1.4-fold P < 0.05) of HS ovaries. These
      results suggest that ovarian autophagy induction occurs in response to HS during
      the follicular phase, and that HS increases anti-apoptotic signaling in oocytes
      and early follicles. These data contribute to the biological understanding of how
      HS acts as an environmental stress to affect follicular development and
      negatively impact reproduction.

PMID- 29025093
TI  - Discharge communication practices and healthcare provider and patient
      preferences, satisfaction and comprehension: A systematic review.
AB  - Purpose: To systematically review the available evidence about hospital discharge
      communication practices and identify which practices were preferred by patients
      and healthcare providers, improved patient and provider satisfaction, and
      increased patients' understanding of their medical condition. Data sources: OVID
      Medline, Web of Science, ProQuest, PubMed and CINAHL plus. Study selection:
      Databases were searched for peer-reviewed, English-language papers, published to
      August 2016, of empirical research using quantitative or qualitative methods.
      Reference lists in the papers meeting inclusion criteria were searched to
      identify further papers. Data extraction: Of the 3489 articles identified, 30 met
      inclusion criteria and were reviewed. Results of data synthesis: Much research to
      date has focused on the use of printed material and person-based discharge
      communication methods including verbal instructions (either in person or via
      telephone calls). Several studies have examined the use of information technology
      (IT) such as computer-generated and video-based discharge communication
      practices. Utilizing technology to deliver discharge information is preferred by
      healthcare providers and patients, and improves patients' understanding of their
      medical condition and discharge instructions. Conclusion: Well-designed IT
      solutions may improve communication, coordination and retention of information,
      and lead to improved outcomes for patients, their families, caregivers and
      primary healthcare providers as well as expediting the task for hospital staff.

PMID- 29025095
TI  - The Mediterranean diet and risk of colorectal cancer in the UK Women's Cohort
      Study.
AB  - Background: Evidence from epidemiological studies investigating associations
      between adherence to the Mediterranean diet and colorectal cancer is
      inconsistent. The aim of this study is to assess in the UK Women's Cohort Study
      whether adherence to the Mediterranean dietary pattern is associated with reduced
      incidence of cancers of the colon and rectum. Method: A total of 35 372 women
      were followed for a median of 17.4 years. A 10-component score indicating
      adherence to the Mediterranean diet was generated for each cohort participant,
      using a 217-item food frequency questionnaire. The Mediterranean diet score
      ranged from 0 for minimal adherence to 10 for maximal adherence. Cox proportional
      hazards regression was used to provide adjusted hazard ratios (HRs) and 95%
      confidence intervals (CIs) for colon and rectal cancer risk. Results: A total of
      465 incident colorectal cancer cases were documented. In the multivariable
      adjusted model, the test for trend was positive (HR = 0.88, 95% CI: 0.78 to 0.99;
      Ptrend = 0.03) for a 2-point increment in the Mediterranean diet score. For
      rectal cancer, a 2-point increment in the Mediterranean diet score resulted in an
      HR (95% CI) of 0.69 (0.56 to 0.86), whereas a 62% linear reduced risk (HR 0.38;
      95% CI: 0.20 to 0.74; Ptrend < 0.001) was observed for women within the highest
      vs the lowest category of the MD score. Estimates for an association with colon
      cancer were weak (Ptrend = 0.41). Conclusions: Findings suggest that women
      adhering to a Mediterranean dietary pattern may have a lower risk of colorectal
      cancer, especially rectal cancer.

PMID- 29025096
TI  - Efficacy of Vibrating Gloves for Chronic Hand Pain due to Osteoarthritis.
AB  - Objective: This study investigated the efficacy of vibration technology for women
      with hand pain due to osteoarthritis (OA) to see if mild compression and small
      vibrating motors were beneficial with periodic use. Methods: Sixty-nine (N = 69)
      women with OA hand pain were randomized into two groups, one that used vibrating
      gloves once a day for 20 minutes (Experimental, N = 34) and one that was
      monitored for three months without gloves (Control, N = 35). All subjects
      completed baseline questionnaires, were administered mechanical quantitative
      sensory testing (QST), and uploaded a smartphone pain app for daily assessment.
      Patients were included if they had chronic pain for more than three months,
      reported a 4 or higher on a 0-10 pain intensity scale, and could speak and
      understand English. Results: In general, compared with the control subjects,
      those in the experimental condition demonstrated reduced pain intensity (P <
      0.05) after using the vibrating gloves. No differences were found between groups
      on activity interference, mood, or sleep. No differences were also noted based on
      age, pain duration, hand dominance, weight, body mass index, or hours sleeping.
      Those with greater sensitivity on QST demonstrated more disability, emotional
      distress, and pain catastrophizing (P < 0.05) but no differences in pain relief
      from or satisfaction with the vibrating gloves. Discussion: Overall, the results
      demonstrated that the vibrating gloves were moderately helpful in reducing hand
      pain in women with OA (53.5%), and most expressed willingness to use the gloves
      (71.4%) and use the pain app (55.8%) in the future. Additional studies to
      determine the mechanism of action of the gloves in managing pain would be
      recommended.

PMID- 29025094
TI  - The descriptive epidemiology of the diurnal profile of bouts and breaks in
      sedentary time in older English adults.
AB  - Background: High sedentary time is associated with adverse metabolic health
      outcomes and mortality in older adults. It has been suggested that breaking up
      sedentary time may be beneficial for metabolic health; however, population
      prevalence data are lacking on the patterns of sedentary behaviour which would
      identify opportunities for intervention. Methods: We used data of adults aged >=
      60 years (n = 3705) from the population-based EPIC-Norfolk cohort, to
      characterize the patterns of total sedentary time, breaks in sedentary time and
      sedentary bouts across the day and assess their associations with participant
      characteristics, using multi-level regression. Sedentary time was measured
      objectively by a hip-mounted accelerometer (ActigraphTM GT1M) worn for 7 days
      during waking time. Results: More than 50% of every waking hour was spent
      sedentary, increasing to a peak of 83% in the evening. On average fewer breaks
      were accrued in the evenings compared with earlier in the day. Marginally more
      sedentary time was accrued on weekend days compared with weekdays (difference 7.4
      min, 95% confidence interval 5.0-9.7). Large proportions of this sedentary time
      appear to be accrued in short bouts (bouts of < 10 min for 32% of the time).
      Older age, being male, being retired, not being in paid employment and having a
      higher body mass index were associated with greater sedentary time and fewer
      breaks. Conclusion: Sedentary time is common throughout the day but peaks in the
      evenings with fewer breaks and longer bouts. We identified a number of
      characteristics associated with sedentary time and additionally inversely
      associated with sedentary breaks, which should inform the development and
      targeting of strategies to reduce sedentary time among older adults.

PMID- 29025097
TI  - Measuring the impact of differences in risk factor distributions on cross
      population differences in disease occurrence: a causal approach.
AB  - Background: In cross-population comparisons of disease occurrence (prevalence,
      incidence), a common public health question is the extent to which variations in
      the distribution of risk factors for the disease explain observed differences.
      Limited work has been done on formalizing this problem, which is conceptually
      tantamount to quantifying the degree of confounding for the 'population effect'
      induced by different factors. A common approach is to compare 'unadjusted' and
      'adjusted' regression-based estimates of that parameter, but the interpretation
      of the resulting 'contribution' measures may be hindered by other confounding
      sources and non-collapsibility issues. Interactions also raise interpretational
      challenges. Methods: We formalized this problem using directed acyclic graphs and
      the potential outcomes framework, on the basis of which we defined a series of
      estimands that address specific questions and are identifiable under certain
      causal assumptions. We subsequently determined possible estimators. A study of
      regional differences in egg allergy prevalence in 1-year-olds was used for
      illustration. Results: The main estimands defined were: the change in the
      prevalence or incidence difference induced by compositional variations in
      measured risk factors, all at once and individually, relative to a reference
      population; and the proportion of the crude difference that remains unexplained
      by measured factors. Standardization (g-computation), inverse probability
      weighted (IPW) and doubly robust IPW estimators of these estimands were
      considered. Conclusions: This work provides a causal theoretical basis for
      studying disease occurrence differences between populations. The proposed
      measures can be used to answer the questions that arise in this context under a
      set of clearly stated assumptions.

PMID- 29025098
TI  - Corrigendum to: Meaningful use of health information technology and declines in
      in-hospital adverse drug events.

PMID- 29025100
TI  - An Examination of Pain's Relationship to Sleep Fragmentation and Disordered
      Breathing Across Common Sleep Disorders.
AB  - Objective: Short sleep duration and insomnia have been linked to higher pain and
      an increased risk of developing chronic pain, but relatively little research has
      examined the contribution of sleep disordered breathing (SDB) to pain. This study
      examined the unique contributions of SDB and insomnia to chronic pain. Subjects:
      Adult patients referred to an academic sleep center for overnight polysomnography
      were invited to participate. Methods: Participants (N = 105) completed
      questionnaires about their sleep and pain, including the Insomnia Severity Index,
      Medical College of Virginia Pain Questionnaire, and two weeks of sleep/pain
      diaries. Results: Most participants (80.00%) reported chronic pain, and the
      likelihood of having chronic pain did not differ by sleep disorder. However,
      there was a significant difference in pain intensity; individuals with comorbid
      obstructive sleep apnea (OSA)/insomnia reported an average pain intensity that
      was 20 points (out of 100) higher than individuals with insomnia or no diagnosis
      and 28 points higher than those with OSA, controlling for participant sex (Ps <
      0.05). In a hierarchical regression, pain was unrelated to measures of sleep
      fragmentation (apnea-hypopnea index, spontaneous arousals, periodic leg movement
      arousals) and nocturnal hypoxemia (SaO2 nadir, time at or below 88% SaO2).
      Conclusions: Polysomnography measures of SDB severity and sleep fragmentation
      were unrelated to pain intensity. However, comorbid OSA/insomnia was associated
      with significantly higher pain (compared with either disorder in isolation), a
      finding that has implications for the treatment of chronic pain and possibly for
      understanding the mechanisms of chronic pain.

PMID- 29025099
TI  - Dutch surgeons' views on the volume-outcome mechanism in surgery: A qualitative
      interview study.
AB  - Objective: To contribute to a better understanding of volume-outcome
      relationships in surgery by exploring Dutch surgeons' views on the underlying
      mechanism. Design: A qualitative study based on face-to-face semi structured
      interviews and an inductive content analysis approach. Setting: Interviews were
      conducted in eight hospitals in the Netherlands (2 university, 4 teaching and 2
      general). Participants: Twenty surgeons (gastrointestinal, vascular and trauma).
      Main outcome measure(s): Dutch surgeons' views on volume-outcome relationships in
      surgery and the underlying mechanism. Results: The majority of surgeons believed
      volume is related to outcomes after surgery. Interviewees highlighted the
      importance of both focus and skills when describing the underlying mechanism.
      Focus was visible on three levels: hospital, surgeon and team. Focus on a
      hospital level referred to investing in specific infrastructure and dedicated
      personnel. Surgeons described both the benefits and downsides of surgeons'
      increased focus to a certain surgical subspeciality. And their experiences on the
      importance of working with fixed, procedure-specific teams. The positive
      influence of caseload on technical and nontechnical skills was acknowledged, as
      well as the benefits of combining skills by operating together. Although a basic
      skill set should be maintained, this does not necessarily require high volume.
      Conclusions: Focus and skills are important explanatory factors in volume-outcome
      relationships according to Dutch surgeons. This suggests that both high- and low
      volume providers should enable specialized, fixed teams for complex surgeries and
      focus on maintenance of both their technical and nontechnical skills. By
      uncovering the underlying mechanism, imperfect quality indicators such as volume
      can be supplemented or replaced.

PMID- 29025101
TI  - New Chapter for Biology of Reproduction.

PMID- 29025103
TI  - Commentary: Intrauterine exposure to artificially sweetened beverages and
      offspring adiposity: is this the tip of the iceberg?

PMID- 29025104
TI  - Implementation of a Brief Abuse and Basic Needs Tool: Impact on Utilization of
      Social Services in Ambulatory Medical Clinics.
AB  - Domestic violence (DV) screening has become increasingly common in recent years;
      however, many organizations still do not practice universal screening, and there
      is considerable debate concerning the best screening tool for detecting DV. The
      current research suggests that a brief tool would be ideal and that existing
      brief tools are comparable to more extensive instruments. Per Joint Commission
      standards, the ambulatory clinics at West Virginia University Hospitals
      instituted the use of the Functional Health Screening (FHS), a three-item tool
      that screens for unexplained weight changes, DV, and basic needs deficits. This
      tool is administered at the beginning of every outpatient clinic visit. This
      study includes a retrospective chart review to investigate the detection rate of
      this tool for DV and basic needs deficits, the increased utilization of social
      services, and nursing attitudes concerning FHS.

PMID- 29025102
TI  - Effects of noncavity-distorting fibroids on endometrial gene expression and
      function.
AB  - Uterine fibroids are a common finding in infertility patients. Impaired
      implantation and decidualization have been proposed to contribute to compromised
      fertility. Data are limited on the endometrial transcriptome from subjects with
      uterine fibroids, as well as endometrial receptivity and decidualization
      potential of endometrial stromal fibroblasts (eSF) from women with fibroids. Our
      objective was to investigate the endometrial transcriptome of women with
      noncavity-distorting intramural fibroids and compare them to control subjects
      with no uterine pathology throughout the menstrual cycle. We also evaluated
      endometrial receptivity gene expression and basic endometrial functions such as
      decidualization, proliferation, and apoptosis in women with fibroid uterus.
      Results showed that large numbers of transcripts were significantly dysregulated
      throughout the menstrual cycle in fibroid subjects compared to controls. However,
      there were essentially no differences in the expression of receptivity markers at
      the tissue level, as well as decidualization markers in tissue and eSF in
      subjects with fibroids compared to controls. However, eSF from women with a
      fibroid uterus exhibited decreased proliferation potential and increased
      apoptosis upon decidualization. These data indicate preserved implantation and
      decidualization potential despite observed gene expression changes in endometrium
      from women with noncavity-distorting fibroids compared to controls. How this
      phenomenon and altered proliferation/apoptosis may contribute to impairment of
      endometrial function in subfertile patients warrants further investigation.

PMID- 29025105
TI  - Pemphigus vulgaris.

PMID- 29025106
TI  - Intense Focused Ultrasound Preferentially Stimulates Transected Nerves Within
      Residual Limbs: Pilot Study.
AB  - Objective: Identifying pain generators in tissue deep in the skin can require
      uncomfortable, complicated, and invasive tests. We describe pilot studies testing
      the hypothesis that ultrasound image-guided, intense focused ultrasound (ig-iFU)
      can noninvasively and differentially stimulate the end of transected nerves in
      the residual limbs of amputee patients. Design: We applied iFU to the transected
      nerve ending as individual pulses with a length of 0.1 seconds using a carrier
      frequency of 2.0 MHz. After targeting, we gradually increased the iFU intensity
      to reach consistent patient-reported stimulation of the transected nerve ending.
      We also stimulated the proximal nerve, tissue near the nerve ending, and the
      intact contralateral nerve. We described the resulting sensations and correlated
      the results of the study participant's pre-iFU study responses to phantom and
      residual limb pain questionnaires. Results: iFU spatial and temporal average
      intensity values between 16 W/cm2 and 433 W/cm2 that were applied to the
      transected nerve ending and proximal nerve elicited sensations, including phantom
      limb sensations, while the same intensity applied to control tissue centimeters
      away from the nerve ending, or to the intact nerve on the contralateral limb, did
      not. Two out of 11 study participants reported only mild and transient pain
      created by iFU stimulation. Successful iFU intensity values correlated with
      neither phantom nor residual limb pain scores. Conclusions: Transected nerves had
      greater sensitivity to iFU stimulation than ipsilateral and contralateral control
      tissue, including intact nerve. These results support the view that ig-iFU may
      one day help physicians identify deep, tender tissue in patients who report
      experiencing pain.

PMID- 29025109
TI  - Commentary: On R. A. Fisher's paper 'The causes of human variability', 1918.

PMID- 29025107
TI  - Vanishing twin syndrome among ART singletons and pregnancy outcomes.
AB  - STUDY QUESTION: Among babies born by ART, do singleton survivors of a vanishing
      twin have lower birth weight than other singletons? SUMMARY ANSWER: Vanishing
      twin syndrome (VTS) was associated with lower birth weight among ART singletons;
      a sibship analysis indicated that the association was not confounded by maternal
      characteristics that remain stable between deliveries. WHAT IS KNOWN ALREADY:
      Previous studies indicate that ART singletons with VTS have increased risk of
      adverse pregnancy outcomes, compared with other ART singletons. The potential
      contribution of unmeasured maternal background characteristics has been unclear.
      STUDY DESIGN, SIZE AND DURATION: This was a Norwegian population-based registry
      study, including 17 368 mothers with 20 410 ART singleton deliveries between
      January 1984 and December 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: The
      study population included 17 291 ART singletons without VTS, 638 ART singletons
      with VTS and 2418 ART singletons with uncertain vanishing twin status. We
      estimated differences in birth weight and gestational age comparing ART
      singletons with VTS first to all ART singletons without VTS, and subsequently to
      their ART siblings without VTS, using random- and fixed-effects linear
      regression, respectively. The corresponding comparisons for the associations with
      preterm birth and small for gestational age (SGA) were conducted using random-and
      fixed-effects logistic regression. The sibling analysis of preterm birth included
      587 discordant siblings, while the sibling analysis of SGA included 674
      discordant siblings. MAIN RESULTS AND THE ROLE OF CHANCE: ART singletons with VTS
      had lower birth weight when compared to all ART singletons without VTS, with an
      adjusted mean difference (95% CI) of -116 g (-165, -67). When we compared ART
      singletons with VTS to their ART singletons sibling without VTS, the adjusted
      mean difference was -112 g (-209, -15). ART singletons with VTS also had
      increased risk of being born SGA, with an adjusted odds ratio (OR) (95% CI) of
      1.48 (1.07, 2.03) compared to all ART singletons without VTS, and 2.79 (1.12,
      6.91) in the sibship analyses. ART singletons with VTS were also more likely to
      be born preterm, although this difference did not reach statistical significance.
      LIMITATIONS REASONS FOR CAUTION: We did not have information on maternal socio
      economic status, but this factor is accounted for in the sibship analyses. We
      also had no information on whether fresh or frozen embryos were replaced. WIDER
      IMPLICATIONS OF THE FINDINGS: The reduction in birth weight and increased risk of
      SGA in ART singletons with VTS may suggest the presence of harmful intrauterine
      factors with long-term health impact. While vanishing twins are not routinely
      observed in naturally conceived pregnancies, loss of a twin is potentially a risk
      factor for the surviving foetus in any pregnancy. This could be further explored
      in large samples of naturally conceived pregnancies with the necessary
      information. STUDY FUNDING/COMPETING INTEREST(S): The authors of this study are
      supported in part by the UK Medical Research Council, US National Institute of
      Environmental Health Sciences and the Norwegian Research Council. The authors
      have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

PMID- 29025110
TI  - Effect of Continuous Local Anesthetic in Post-Cardiac Surgery Patients: A
      Systematic Review.
AB  - Objective: The purpose of this review was to determine the effect of CLA infusion
      post cardiac surgery on pain, time to ambulation, severe adverse events, patient
      satisfaction, time to extubation, length of stay in the intensive care unit and
      in the hospital, total narcotic consumption, and pulmonary function. Design:
      Systematic review with meta-analysis (PROSPERO CRD42014010188). Methods: We
      searched the following electronic databases: the Cochrane Central Register of
      Controlled Trials (CENTRAL); MEDLINE; EMBASE; CINAHL; Allied and Complementary
      Medicine (AMED); and PsycINFO; as well as hand-searching cardiothoracic surgery
      and anesthetic journals and meeting abstracts. Results: Ten eligible trials with
      a total of 546 participants were identified. Meta-analyses showed that CLA
      infusion significantly reduced the total mean visual analog pain score at 72
      hours (mean difference [MD] = -14.31 mm, 95% confidence interval [CI] = -25.59 to
      -3.03); time to ambulation (MD = -2.81 hours, 95% CI = -5.23 to -0.4); morphine
      requirement (MD = -10.19 mg, 95% CI = -11.80 to -8.58) but did not reduce time to
      ambulate to chair (MD = -1.65 hours, 95% CI = -4.04 to 0.74); time to extubation
      (MD = -0.18 hours, 95% CI = -1.24 to 0.89); length of ICU stay (MD = 0.9 hours,
      95% CI = -2.96 to 4.75); and hospital length of stay (MD = -0.59 days, 95% CI = 
      1.24 to 0.07). There were insufficient data to perform a meta-analysis on severe
      adverse events, patient satisfaction, or pulmonary function. Conclusions: CLA
      infusion after cardiac surgery reduces pain score at 72 hours, shortens time to
      ambulation, and reduces morphine consumption at 48 hours.

PMID- 29025111
TI  - Protective effects of household-based TB interventions are robust to
      neighbourhood-level variation in exposure risk in Lima, Peru: a model-based
      analysis.
AB  - Background: Untargeted active screening and treatment programmes for tuberculosis
      (TB) have not been shown to be more effective than passive screening and
      isoniazid preventive therapy (IPT) for reducing TB incidence. In this manuscript,
      we compare the efficacy of targeting screening and IPT on high-risk household
      contacts of diagnosed TB cases, with less-targeted active screening approaches in
      Lima, Peru. Methods: We conducted a population-based prospective cohort study
      within households of TB cases in Lima. We identified all adults diagnosed with
      incident pulmonary TB from 2009 through 2012 at 106 participating public health
      centres (HC) within our catchment area of ~3.3 million inhabitants. We estimated
      combined effects of community and household exposure on the risk of latent TB
      infection (LTBI) and incident TB disease. We used simulation modelling to assess
      the efficacy of TB screening programmes for reducing the risk of incident TB in
      these contacts. Results: Individuals with household exposure to TB are more
      likely to present with LTBI and TB disease than those without this exposure,
      despite wide variation in community exposure. Simulations suggest that more cases
      are prevented by 1000 administrations of IPT to tuberculin skin test (TST)
      positive household contacts of identified TB cases (30, 95% CI = 16,47) than from
      blanket screening and treatment in the community (7, 95% CI = 2,17). Conclusions:
      Household exposure remains a major driver of incident TB risk among household
      contacts of identified TB cases. Targeting interventions on these individuals is
      likely to prevent more cases of TB than blanket screening of individuals in the
      community.

PMID- 29025108
TI  - HDL-cholesterol levels and risk of age-related macular degeneration: a
      multiethnic genetic study using Mendelian randomization.
AB  - Background: Dyslipidemia, particularly high-density lipoprotein cholesterol (HDL
      C), has recently been implicated in the pathogenesis of age-related macular
      degeneration (AMD), the leading cause of vision loss. However, epidemiological
      studies have yielded conflicting results. Methods: We investigated the causal
      role of plasma lipid levels in AMD in multiethnic populations comprising 16 144
      advanced AMD cases and 17 832 controls of European descent, together with 2219
      cases and 5275 controls of Asian descent, using Mendelian randomization in three
      models. Model 1 is a conventional meta-analysis which does not account for
      pleiotropy of instrumental variable (IV) effects. Model 2 is a univariate,
      inverse variance weighted regression analysis that accounts for potential
      unbalanced pleiotropy using MR-Egger method. Finally, Model 3 is a multivariate
      regression analysis that addresses pleiotropy by MR-Egger method and by adjusting
      for effects on other lipid traits. Results: A 1 standard deviation (SD) higher
      HDL-cholesterol level was associated with an odds ratio (OR) for AMD of 1.17 (95%
      confidence interval: 1.07-1.29) in Europeans (P = 6.88 * 10-4) and of 1.58 (1.24
      2.00) in Asians (P = 2.92 * 10-4) in Model 3. The corresponding OR estimates were
      1.30 (1.09-1.55) in Europeans (P = 3.18 * 10-3) and 1.42 (1.11-1.80) in Asians (P
      = 4.42 * 10-3) in Model 1, and 1.21 (1.11-1.31) in Europeans (P = 3.12 * 10-5)
      and 1.51 (1.20-1.91) in Asians (P = 7.61 * 10-4) in Model 2. Conversely, neither
      LDL-C (Europeans: OR = 0.96, P = 0.272; Asians: OR = 1.02, P = 0.874; Model 3)
      nor triglyceride levels (Europeans: OR = 0.91, P = 0.102; Asians: OR = 1.06, P =
      0.613) were associated with AMD. We also assessed the association between lipid
      levels and polypoidal choroidal vasculopathy (PCV) in Asians, a subtype of AMD,
      and found a similar trend for association of PCV with HDL-C levels. Conclusions:
      Our study shows that high levels of plasma HDL-C are causally associated with an
      increased risk for advanced AMD in European and Asian populations, implying that
      strategies reducing HDL-C levels may be useful to prevent and treat AMD.

PMID- 29025112
TI  - Sodium Phosphate Enemas do not Worsen Renal Function amongst Hospitalized
      Patients with Mild to Moderate Renal Failure. A Matched, Case-control study.
AB  - Background: Sodium Phosphate enemas (SPEs) are widely used amongst hospitalized
      patients despite their potential to worsen renal failure. The extent to which
      this side effect is clinically relevant is questionable. Methods: We conducted a
      matched case-control, retrospective study in a cohort of hospitalized patients.
      Patients treated and untreated with SPEs were matched for age, gender, baseline
      creatinine, usage of certain medications and several background diagnoses. Three
      groups of matched patients (whole study cohort, patients with baseline creatinine
      > 1.5 mg/dL and those with baseline creatinine > 2 mg/dL) were compared with
      regards to their creatinine and blood electrolyte concentrations during 3
      consecutive hospitalization days after SPE application. Results: 412 patients
      were included in this study of which 206 were treated by single SPEs. Exact
      matching was done for the whole study cohort, for 108 patients with baseline
      creatinine > 1.5 mg/dL and for 58 patients with baseline creatinine > 2 mg/dL.
      During 3 consecutive days after SPEs, the maximal blood concentrations of
      creatinine, phosphor and potassium did not differ significantly between treated
      patients and matched controls, in all 3 patients' groups. Conclusion: Application
      of sodium phosphate enemas do not seem to worsen mild to moderate renal failure,
      nor are associated with hyperphosphatemia or hyperkalemia in patients
      hospitalized in internal medicine departments.

PMID- 29025113
TI  - Innovative Technology Using Virtual Reality in the Treatment of Pain: Does It
      Reduce Pain via Distraction, or Is There More to It?
AB  - Objective: Virtual reality (VR) is an exciting new technology with almost endless
      possible uses in medicine. One area it has shown promise is pain management. This
      selective review focused on studies that gave evidence to the distraction or
      nondistraction mechanisms by which VR leads to the treatment of pain. Methods:
      The review looked at articles from 2000 to July 29, 2016, focusing on studies
      concerning mechanisms by which virtual reality can augment pain relief. The data
      was collected through a search of MEDLINE and Web of Science using the key words
      of "virtual reality" and "pain" or "distraction." Results: Six studies were
      identified: four small randomized controlled studies and two prospective/pilot
      studies. The search results provided evidence that distraction is a technique by
      which VR can have benefits in the treatment of pain. Both adult and pediatric
      populations were included in these studies. In addition to acute pain, several
      studies looked at chronic pain states such as headaches or fibromyalgia. These
      studies also combined VR with other treatment modalities such as biofeedback
      mechanisms and cognitive behavioral therapy. Conclusions: These results
      demonstrate that in addition to distraction, there are novel mechanisms for VR
      treatment in pain, such as producing neurophysiologic changes related to
      conditioning and exposure therapies. If these new mechanisms can lead to new
      treatment options for patients with chronic pain, VR may have the ability to help
      reduce opioid use and misuse among chronic pain patients. More studies are needed
      to reproduce results from prospective/pilot studies in large randomized control
      studies.

PMID- 29025114
TI  - Comprehensive process model of clinical information interaction in primary care:
      results of a "best-fit" framework synthesis.
AB  - Objective: To describe a new, comprehensive process model of clinical information
      interaction in primary care (Clinical Information Interaction Model, or CIIM)
      based on a systematic synthesis of published research. Materials and Methods: We
      used the "best fit" framework synthesis approach. Searches were performed in
      PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature
      (CINAHL), PsycINFO, Library and Information Science Abstracts, Library,
      Information Science and Technology Abstracts, and Engineering Village. Two
      authors reviewed articles according to inclusion and exclusion criteria. Data
      abstraction and content analysis of 443 published papers were used to create a
      model in which every element was supported by empirical research. Results: The
      CIIM documents how primary care clinicians interact with information as they make
      point-of-care clinical decisions. The model highlights 3 major process
      components: (1) context, (2) activity (usual and contingent), and (3) influence.
      Usual activities include information processing, source-user interaction,
      information evaluation, selection of information, information use, clinical
      reasoning, and clinical decisions. Clinician characteristics, patient behaviors,
      and other professionals influence the process. Discussion: The CIIM depicts the
      complete process of information interaction, enabling a grasp of relationships
      previously difficult to discern. The CIIM suggests potentially helpful
      functionality for clinical decision support systems (CDSSs) to support primary
      care, including a greater focus on information processing and use. The CIIM also
      documents the role of influence in clinical information interaction; influencers
      may affect the success of CDSS implementations. Conclusion: The CIIM offers a new
      framework for achieving CDSS workflow integration and new directions for CDSS
      design that can support the work of diverse primary care clinicians.

PMID- 29025115
TI  - Granulomatosis with polyangiitis as the differential diagnosis.

PMID- 29025116
TI  - Applications of network analysis to routinely collected health care data: a
      systematic review.
AB  - Objective: To survey network analyses of datasets collected in the course of
      routine operations in health care settings and identify driving questions,
      methods, needs, and potential for future research. Materials and Methods: A
      search strategy was designed to find studies that applied network analysis to
      routinely collected health care datasets and was adapted to 3 bibliographic
      databases. The results were grouped according to a thematic analysis of their
      settings, objectives, data, and methods. Each group received a methodological
      synthesis. Results: The search found 189 distinct studies reported before August
      2016. We manually partitioned the sample into 4 groups, which investigated
      institutional exchange, physician collaboration, clinical co-occurrence, and
      workplace interaction networks. Several robust and ongoing research programs were
      discerned within (and sometimes across) the groups. Little interaction was
      observed between these programs, despite conceptual and methodological
      similarities. Discussion: We use the literature sample to inform a discussion of
      good practice at this methodological interface, including the concordance of
      motivations, study design, data, and tools and the validation and standardization
      of techniques. We then highlight instances of positive feedback between
      methodological development and knowledge domains and assess the overall cohesion
      of the sample.

PMID- 29025117
TI  - Preliminary Investigation of Workplace-Provided Compressed Mindfulness-Based
      Stress Reduction with Pediatric Medical Social Workers.
AB  - Mindfulness practices, including mindfulness meditation, show promise for
      decreasing stress among health care providers. This exploratory study
      investigates the feasibility of a two-day compressed mindfulness-based stress
      reduction (cMBSR) course provided in the hospital workplace with pediatric health
      care social workers. The standard course of Jon Kabat-Zinn's MBSR requires a
      participant commitment to eight weeks of instruction consisting of one 2.5-hour
      per-week class, a single day retreat, and 45 minutes of practice for six of seven
      days each week. Commitments to family, work, caregiving, education, and so on, as
      well as limitations such as distance, may prevent health care providers from
      participating in a standard MBSR course. Using t tests, researchers measured the
      effect of cMBSR on (a) positive and negative experiences in pediatric social
      work, (b) perceived stress, (c) mindfulness, and (d) caring self-efficacy (as a
      component of patient- and family-centered care). Results included significant
      differences between the pre- and post-intervention outcome variables on the
      Professional Quality of Life Secondary Traumatic Stress subscale, the Mindful
      Attention and Awareness Scale, and the Caring Efficacy Scale. Findings found
      adequate evidence for the feasibility of cMBSR design and for a need of a more
      rigorous study of the effects of the cMBSR intervention.

PMID- 29025118
TI  - Cohort Profile: The Australian Longitudinal Study on Women's Health (ALSWH) 1989
      95 cohort.

PMID- 29025119
TI  - Response to Unit conversions between LOINC codes.

PMID- 29025120
TI  - Cohort Profile: The Atlantic Partnership for Tomorrow's Health (Atlantic PATH)
      Study.

PMID- 29025121
TI  - Acute ocular ischemic syndrome.

PMID- 29025123
TI  - Comparative epidemiology of Clostridium difficile infection: England and the USA.
AB  - Objective: To examine whether there is an epidemiological difference between
      Clostridium difficile infection (CDI) inpatient populations in England and the
      United States. Design: A cross-sectional study. Setting: National administrative
      inpatient discharge data from England (Hospital Episode Statistics) and the USA
      (National Inpatient Sample) in 2012. Participants: De-identifiable non-obstetric
      inpatient discharges from the national datasets were used to estimate national
      CDI incidence in the United States and England using ICD9-CM(008.45) and
      ICD10(A04.7) respectively. Main outcome measures: The rate of CDI was calculated
      per 100 000 population using national population estimates. Rate per 100 000
      inpatient discharges was also calculated separated by primary and secondary
      diagnosis of CDI. Age, sex and Elixhauser comorbidities profiles were examined.
      Results: The USA had a higher rate of CDI compared to England: 115.1/100 000 vs.
      19.3/100 000 population (P < 0.001). CDI age profiles differed between the
      countries (P < 0.001): in England, patients >=75 years constitute a larger
      proportion of CDI cases, whilst those aged 25-70 constitute more cases in the US
      (P < 0.001). Overall adjusted odds of CDI in females compared to males was
      elevated in both England (odds ratios (OR) 1.26 95% CI [1.21,1.31] P < 0.001) and
      the USA (OR 1.20 95% CI [1.18,1.22] P < 0.001). The proportion of CDI patients
      with comorbidities was greater in the USA compared to England apart from
      dementia, which was greater in England (9.63% vs. 1.25%, P < 0.0001).
      Conclusions: The 2012 inpatient CDI rate within the USA was much higher than in
      England. Age and comorbidity profiles also differed between CDI patients in both
      countries. The reasons for this are likely multi-factorial but may reflect
      national infection control policy.

PMID- 29025124
TI  - Increasing incidence of chronic subdural haematoma in the elderly.

PMID- 29025122
TI  - Software Application Profile: Opal and Mica: open-source software solutions for
      epidemiological data management, harmonization and dissemination.
AB  - Motivation: Improving the dissemination of information on existing
      epidemiological studies and facilitating the interoperability of study databases
      are essential to maximizing the use of resources and accelerating improvements in
      health. To address this, Maelstrom Research proposes Opal and Mica, two inter
      operable open-source software packages providing out-of-the-box solutions for
      epidemiological data management, harmonization and dissemination. Implementation:
      Opal and Mica are two standalone but inter-operable web applications written in
      Java, JavaScript and PHP. They provide web services and modern user interfaces to
      access them. General features: Opal allows users to import, manage, annotate and
      harmonize study data. Mica is used to build searchable web portals disseminating
      study and variable metadata. When used conjointly, Mica users can securely query
      and retrieve summary statistics on geographically dispersed Opal servers in real
      time. Integration with the DataSHIELD approach allows conducting more complex
      federated analyses involving statistical models. Availability: Opal and Mica are
      open-source and freely available at [www.obiba.org] under a General Public
      License (GPL) version 3, and the metadata models and taxonomies that accompany
      them are available under a Creative Commons licence.

PMID- 29025125
TI  - How well do general practitioners manage laboratory test results for patients
      with diabetes mellitus and cardiovascular disease?: A systematic review.
AB  - Purpose: To evaluate how well general practitioners (GPs) manage and respond to
      laboratory results for patients with diabetes mellitus (DM) and cardiovascular
      disease (CVD). Data sources: MEDLINE, CINAHL, Embase, EBM reviews, ProQuest and
      Scopus. Study selection: Peer-reviewed journal articles published between 2000
      and 2015 that assessed GPs' management of laboratory results for patients with DM
      or CVD. Data extraction: Study design and demographics, laboratory tests and key
      findings relating to GP management of laboratory results were extracted from
      studies. Results of data synthesis: Thirteen articles were included, comprising
      seven studies which utilized surveys, four observational studies, one cohort
      study and one randomized controlled trial. Findings indicate that GPs often
      overestimate the risk of complications associated with DM and CVD based on
      laboratory results and have unrealistically high expectations regarding the
      precision of laboratory tests. Considerable variation existed in the use of
      repeat testing for diagnostic confirmation and in GPs' identification of the
      difference between two consecutive results required to indicate a change in
      patient condition. GPs also often failed to initiate appropriate treatment for
      patients with DM and CVD based on laboratory results. Feedback to GPs about their
      test ordering patterns and educational messages on laboratory results improved
      clinical outcomes. Conclusion: Evidence about how well GPs manage results and its
      impact on patient outcomes remains weak and inconclusive. This review identified
      a number of areas where interventions could support GPs to improve the
      interpretation and management of laboratory test results, including feedback to
      GPs and educational messages on test result reports.

PMID- 29025126
TI  - Patients' emotions: reacting is not enough.

PMID- 29025128
TI  - Opioid Therapy for Chronic Pain: Overview of the 2017 US Department of Veterans
      Affairs and US Department of Defense Clinical Practice Guideline.
AB  - Description: The US Department of Veterans Affairs (VA) and US Department of
      Defense (DoD) revised the 2010 clinical practice guideline (CPG) for the
      management of opioid therapy for chronic pain, considering the specific needs of
      the VA and DoD and new evidence regarding prescribing opioid medication for non
      end-of-life-related chronic pain. This paper summarizes the major recommendations
      and compares them with the US Centers for Disease Control and Prevention (CDC)
      guideline for prescribing opioids. Patient Population: This Opioid Therapy CPG
      was developed for VA-DoD service members, veterans, and their families. Methods:
      The VA/DoD Evidence-Based Practice Work Group convened a VA/DoD guideline renewal
      development effort and conformed to the guidelines established by the VA/DoD
      Joint Executive Council (JEC) and VA/DoD Health Executive Council (HEC). The
      panel developed questions, searched and evaluated the literature, developed
      recommendations using GRADE methodology, and developed algorithms. Passage of the
      CARA Act by Congress compelled consideration and comparison with the CDC opioid
      therapy guideline mid-development. Results: There were 18 recommendations made.
      This article focuses on guideline development and key recommendations with CDC
      comparisons taken from four major areas, including: initiation and continuation
      of opioids;type, dose, follow-up, and taper of opioids;risk mitigation;acute
      pain. Conclusions: Guideline development and recommendations are presented. There
      was substantial overlap with the CDC opioid guideline. Additionally, there were
      items particularly relevant to the VA-DoD, including risk mitigation, suicide
      prevention, and preventing opioid use disorder in young patients. Our guideline
      highlights avoiding opioid therapy longer than 90 days as a critical juncture.

PMID- 29025127
TI  - Are participants concerned about privacy and security when using short message
      service to report product adherence in a rectal microbicide trial?
AB  - Objective: During a Phase 2 rectal microbicide trial, men who have sex with men
      and transgender women (n = 187) in 4 countries (Peru, South Africa, Thailand,
      United States) reported product use daily via short message service (SMS). To
      prevent disclosure of study participation, the SMS system program included
      privacy and security features. We evaluated participants' perceptions of privacy
      while using the system and acceptability of privacy/security features. Materials
      and Methods: To protect privacy, the SMS system: (1) confirmed participant
      availability before sending the study questions, (2) required a password, and (3)
      did not reveal product name or study participation. To ensure security, the
      system reminded participants to lock phone/delete messages. A computer-assisted
      self-interview (CASI), administered at the final visit, measured burden of
      privacy and security features and SMS privacy concerns. A subsample of 33
      participants underwent an in-depth interview (IDI). Results: Based on CASI, 85%
      had no privacy concerns; only 5% were very concerned. Most were not bothered by
      the need for a password (73%) or instructions to delete messages (82%). Based on
      IDI, reasons for low privacy concerns included sending SMS in private or feeling
      that texting would not draw attention. A few IDI participants found the password
      unnecessary and more than half did not delete messages. Discussion: Most
      participants were not concerned that the SMS system would compromise their
      confidentiality. SMS privacy and security features were effective and not
      burdensome. Conclusion: Short ID-related passwords, ambiguous language, and
      reminders to implement privacy and security-enhancing behaviors are recommended
      for SMS systems.

PMID- 29025129
TI  - Perspective: Filling the Educational Void.

PMID- 29025130
TI  - Domain-specific physical activity and sedentary behaviour in relation to colon
      and rectal cancer risk: a systematic review and meta-analysis.
AB  - Background: Physical activity is associated with reduced risk of colorectal
      cancer, but most epidemiological studies have focused on occupational and
      recreational physical activity. The evidence for other domains of activity, and
      for sedentary behaviour, is limited. Methods: Medline, Embase and Web of Science
      were searched from inception to December 2015 for studies examining domain
      specific physical activity or sedentary behaviour and the risk of colon and/or
      rectal cancer. We extracted maximally adjusted relative risks (RRs) except when
      RRs not adjusted for body mass index, were also presented. We used random-effects
      meta-analysis to compute pooled RRs comparing the highest versus the lowest level
      of exposure. We used meta-regression to assess sources of heterogeneity in
      estimates. Results: We identified 17 cohort and 21 case-control studies, of which
      17 had occupational data, 23 had recreational data, three each had data on
      transport and household physical activity domains, and 6 studies had data on
      occupational sedentary behaviour. The pooled relative risks (RRs) for colon
      cancer were 0.74 (95% confidence interval (CI): 0.67, 0.82) for occupational
      activity, 0.80 (95% CI: 0.71, 0.89) for recreational activity, 0.66 (95% CI:
      0.45, 0.98) for transport-related physical activity, 0.85 (95% CI: 0.71, 1.02)
      for household physical activity, and 1.44 (95% CI: 1.28, 1.62) for occupational
      sedentary behaviour. For rectal cancer, the pooled RRs were 0.88 (95% CI: 0.79,
      0.98) for occupational activity, 0.87 (95% CI: 0.75, 1.01) for recreational
      activity, 0.88 (95% CI: 0.70, 1.12) for transport-related physical activity, 1.01
      (95% CI: 0.80, 1.27) for household physical activity, and 1.02 (95% CI: 0.82,
      1.28) for occupational sedentary behaviour. Conclusions: In addition to
      increasing occupational and recreational physical activity, promoting physical
      activity during transport and reducing sedentary behaviour in the workplace may
      also be useful colorectal cancer prevention strategies.

PMID- 29025131
TI  - A guide to evaluating linkage quality for the analysis of linked data.
AB  - Linked datasets are an important resource for epidemiological and clinical
      studies, but linkage error can lead to biased results. For data security reasons,
      linkage of personal identifiers is often performed by a third party, making it
      difficult for researchers to assess the quality of the linked dataset in the
      context of specific research questions. This is compounded by a lack of guidance
      on how to determine the potential impact of linkage error. We describe how
      linkage quality can be evaluated and provide widely applicable guidance for both
      data providers and researchers. Using an illustrative example of a linked dataset
      of maternal and baby hospital records, we demonstrate three approaches for
      evaluating linkage quality: applying the linkage algorithm to a subset of gold
      standard data to quantify linkage error; comparing characteristics of linked and
      unlinked data to identify potential sources of bias; and evaluating the
      sensitivity of results to changes in the linkage procedure. These approaches can
      inform our understanding of the potential impact of linkage error and provide an
      opportunity to select the most appropriate linkage procedure for a specific
      analysis. Evaluating linkage quality in this way will improve the quality and
      transparency of epidemiological and clinical research using linked data.

PMID- 29025133
TI  - Offspring risk of obesity in childhood, adolescence and adulthood in relation to
      gestational diabetes mellitus: a sex-specific association.

PMID- 29025132
TI  - Most Relevant Neuropathic Pain Treatment and Chronic Low Back Pain Management
      Guidelines: A Change Pain Latin America Advisory Panel Consensus.
AB  - Objective: Chronic pain conditions profoundly affect the daily living of a
      significant number of people and are a major economic and social burden,
      particularly in developing countries. The Change Pain Latin America (CPLA)
      advisory panel aimed to identify the most appropriate guidelines for the
      treatment of neuropathic pain (NP) and chronic low back pain (CLBP) for use
      across Latin America. Methods: Published systematic reviews or practice
      guidelines were identified by a systematic search of PubMed, the Guidelines
      Clearinghouse, and Google. Articles were screened by an independent reviewer, and
      potential candidate guidelines were selected for more in-depth review. A
      shortlist of suitable guidelines was selected and critically evaluated by the
      CPLA advisory panel. Results: Searches identified 674 and 604 guideline articles
      for NP and CLBP, respectively. Of these, 14 guidelines were shortlisted for
      consensus consideration, with the following final selections made:
      "Recommendations for the pharmacological management of neuropathic pain from the
      Neuropathic Pain Special Interest Group in 2015-pharmacotherapy for neuropathic
      pain in adults: A systematic review and meta-analysis.""Diagnosis and treatment
      of low back pain: A joint clinical practice guideline from the American College
      of Physicians and the American Pain Society" (2007). Conclusions: The selected
      guidelines were endorsed by all members of the CPLA advisory board as the best
      fit for use across Latin America. In addition, regional considerations were
      discussed and recorded. We have included this expert local insight and advice to
      enhance the implementation of each guideline across all Latin American countries.

PMID- 29025135
TI  - Current Perspective on the Use of Opioids in Perioperative Medicine: An Evidence
      Based Literature Review, National Survey of 70,000 Physicians, and
      Multidisciplinary Clinical Appraisal.
AB  - Objective: Opioids represent an important analgesic option for physicians
      managing acute pain in surgical patients. Opioid management is not without its
      drawbacks, however, and current trends suggest that opioids might be overused in
      the United States. An expert panel was convened to conduct a clinical appraisal
      regarding the use of opioids in the perioperative setting. Methods: The clinical
      appraisal consisted of the review, presentation, and assessment of current
      published evidence as it relates to the statement "Opioids are not overused in
      the United States, even though opioid adjunct therapy achieves greater pain
      control with less risk." The authors' evaluation of this statement was also
      compared with the results of a national survey of surgeons and anesthesiologists
      in the United States. Results: We report the presented literature and proceedings
      of the panel discussion. The national survey revealed a wide range of opinions
      regarding opioid overuse in the United States. Current published evidence
      provides support for the efficacy of opioid therapy in surgical patients;
      however, it is not sufficient to conclude unequivocally that opioids are-or are
      not-overused in the management of acute surgical pain in the United States.
      Conclusions: Opioids remain a key component of multimodal perioperative
      analgesia, and strategic opioid use based on clinical considerations and patient
      specific needs represents an opportunity to support improved postoperative
      outcomes and satisfaction. Future studies should focus on identifying optimal
      procedure-specific and patient-centered approaches to multimodal perioperative
      analgesia.

PMID- 29025136
TI  - Predictors of Responsivity to Interdisciplinary Pain Management.
AB  - Objective: This study investigated for whom interdisciplinary pain management
      (IPM) is most effective. Identification of predictors of treatment responsivity
      would facilitate development of patient-treatment matching algorithms to optimize
      outcomes. Design: Repeated measures prospective study of consecutive admissions
      to a two-week IPM program. Setting: Brisbane Pain Rehabilitation Service in
      Brisbane, Australia. Subjects: A total of 163 adults referred for chronic pain
      management. Methods: Self-report questionnaires and measures of physical
      performance were obtained at program entry and completion. Group-level analyses
      were performed using standard parametric statistics. Individual-level change was
      assessed using recommended criteria. Multivariate analysis of variance and
      logistic regression were used to examine outcomes and predictors of response.
      Results: Significant improvements were observed across psychological, social, and
      physical outcome domains. Up to 50% of participants had clinically meaningful
      improvements, while less than 10% deteriorated. Higher baseline depression,
      anxiety, stress, and pain catastrophizing scores predicted better group-level
      outcomes (Ps < 0.05). Participants with higher baseline depression scores were
      most likely to show significant individual-level improvement on at least one
      outcome (Ps < 0.05). Participants with nociceptive pain were more than four times
      more likely than those with neuropathic pain to show clinically meaningful
      improvement on multiple outcomes, while those participants who were older were
      more likely to be multidomain responders. Conclusions: Physical, psychological,
      and social outcomes all improved in a significant proportion of participants
      following the IPM. High baseline depression was a clinically reliable predictor
      of individual-level improvement. Individuals with nociceptive pain and those who
      were older, respectively, showed the largest response across multiple outcomes
      and domains.

PMID- 29025134
TI  - Cannabis Dampens the Effects of Music in Brain Regions Sensitive to Reward and
      Emotion.
AB  - Background: Despite the current shift towards permissive cannabis policies, few
      studies have investigated the pleasurable effects users seek. Here, we
      investigate the effects of cannabis on listening to music, a rewarding activity
      that frequently occurs in the context of recreational cannabis use. We
      additionally tested how these effects are influenced by cannabidiol, which may
      offset cannabis-related harms. Methods: Across 3 sessions, 16 cannabis users
      inhaled cannabis with cannabidiol, cannabis without cannabidiol, and placebo. We
      compared their response to music relative to control excerpts of scrambled sound
      during functional Magnetic Resonance Imaging within regions identified in a meta
      analysis of music-evoked reward and emotion. All results were False Discovery
      Rate corrected (P<.05). Results: Compared with placebo, cannabis without
      cannabidiol dampened response to music in bilateral auditory cortex (right:
      P=.005, left: P=.008), right hippocampus/parahippocampal gyrus (P=.025), right
      amygdala (P=.025), and right ventral striatum (P=.033). Across all sessions, the
      effects of music in this ventral striatal region correlated with pleasure ratings
      (P=.002) and increased functional connectivity with auditory cortex (right: P<
      .001, left: P< .001), supporting its involvement in music reward. Functional
      connectivity between right ventral striatum and auditory cortex was increased by
      cannabidiol (right: P=.003, left: P=.030), and cannabis with cannabidiol did not
      differ from placebo on any functional Magnetic Resonance Imaging measures. Both
      types of cannabis increased ratings of wanting to listen to music (P<.002) and
      enhanced sound perception (P<.001). Conclusions: Cannabis dampens the effects of
      music in brain regions sensitive to reward and emotion. These effects were offset
      by a key cannabis constituent, cannabidol.

PMID- 29025137
TI  - Hypoparathyroidism, Deafness & Renal Dysplasia (HDR) Syndrome & GATA3.

PMID- 29025138
TI  - Relative Bioavailability, Intranasal Abuse Potential, and Safety of
      Benzhydrocodone/Acetaminophen Compared with Hydrocodone Bitartrate/Acetaminophen
      in Recreational Drug Abusers.
AB  - Objectives: Benzhydrocodone is a hydrocodone prodrug that has been combined with
      acetaminophen (APAP) in a novel immediate-release analgesic. This study evaluated
      the relative bioavailability, intranasal abuse potential, and safety of
      benzhydrocodone/APAP compared with commercially available hydrocodone bitartrate
      (HB)/APAP. Design: Single-center, randomized, double-blind, double-dummy, two
      part study comprising a Dose Selection (Part A) phase and a Main Study (Part B)
      phase. Setting: Clinical research site. Subjects: Healthy adult, nondependent,
      recreational opioid users with a history of intranasal abuse. Methods: Subjects
      (N = 42) in Part B received five in-clinic treatments consisting of intranasal
      and oral benzhydrocodone/APAP (13.34/650 mg), intranasal and oral
      hydrocodone/APAP (15/650 mg), and placebo, with four or more days of washout
      between treatments. Pharmacodynamic assessments included subjective effects of
      Drug Liking, Overall Drug Liking, and Take Drug Again (assessed on visual analog
      scale [VAS]), as well as nasal irritation. Pharmacokinetics and safety were also
      assessed. Results: Hydrocodone Cmax was 11% lower for intranasal
      benzhydrocodone/APAP vs intranasal HB/APAP (P = 0.0027). Early cumulative
      hydrocodone exposures for intranasal benzhydrocodone/APAP through 0.5, 1, and 2
      hours were reduced by approximately 50%, 29%, and 15%, respectively (P <=
      0.0024). Correspondingly, Drug Liking VAS values up to two hours postdose were
      significantly lower for intranasal benzhydrocodone/APAP vs intranasal HB/APAP (P
      <= 0.0079), although peak Drug Liking VAS (Emax) scores were not different (P =
      0.2814). Adverse nasal effects were more frequent for intranasal
      benzhydrocodone/APAP vs intranasal HB/APAP. Conclusions: Reduced hydrocodone
      exposure and drug liking at early time intervals, coupled with adverse nasal
      effects, can be expected to provide a level of deterrence to the intranasal route
      of abuse for benzhydrocodone/APAP.

PMID- 29025139
TI  - Steeple sign and acute laryngotracheobronchitis.

PMID- 29025140
TI  - Policies and strategies to facilitate secondary use of research data in the
      health sciences.

PMID- 29025141
TI  - How is it best to deliver care in acute medical units? A systematic review.
AB  - The majority of medical patients presenting to hospital in the UK are cared for
      in acute medical units (AMUs). Such units are also increasingly present
      internationally. Care delivery varies across units: this review aims to examine
      the evidence for how best to deliver AMU care.Six electronic databases and grey
      literature were searched. Inclusion criteria comprised interventions applied to
      undifferentiated patients in AMU settings. All studies were quality assessed. A
      narrative approach was undertaken.Nine studies, all conducted in the UK or
      Ireland, evaluated 1.3 million episodes, 3617 patients and 49 staff. There was
      single study evidence for beneficial effects of: enhanced pharmacy care, a
      dedicated occupational therapy service, an all-inclusive consultant work pattern,
      a rapid-access medical clinic and formalized handovers. Two studies found
      increased consultant presence was associated with reduced mortality; one of these
      studies found an association with a reduction in 28-day readmissions; and the
      other found an association with an increased proportion of patients discharged on
      the day they were admitted. Three studies provide evidence of the beneficial
      effects of multiple interventions developed from local service reviews.Overall,
      the quality of the evidence was limited. This review has identified operationally
      relevant evidence that increased consultant presence is associated with improved
      outcomes of care; has highlighted the potential to improve outcomes locally
      through service reviews; and has demonstrated an important knowledge gap of how
      best to deliver AMU care. These findings have importance given the challenges
      acute services currently face.

PMID- 29025142
TI  - Community acquired acute kidney injury: findings from a large population cohort.
AB  - Background: The extent of patient contact with medical services prior to
      development of community acquired-acute kidney injury (CA-AKI)is unknown. Aim: We
      examined the relationship between incident CA-AKI alerts, previous contact with
      hospital or primary care and clinical outcomes. Design: A prospective national
      cohort study of all electronic AKIalerts representing adult CA-AKI. Methods: Data
      were collected for all cases of adult (>=18 years of age) CA-AKI in Wales between
      1 November 2013 and 31 January 2017. Results: There were a total of 50 560
      incident CA-AKI alerts. In 46.8% there was a measurement of renal function in the
      30 days prior to the AKI alert. In this group, in 63.8% this was in a hospital
      setting, of which 37.6% were as an inpatient and 37.5% in Accident and Emergency.
      Progression of AKI to a higher AKI stage (13.1 vs. 9.8%, P < 0.001) (or for AKI 3
      an increase of > 50% from the creatinine value generating the alert), the
      proportion of patients admitted to Intensive Care (5.5 vs. 4.9%, P = 0.001) and
      90-day mortality (27.2 vs. 18.5%, P < 0.001) was significantly higher for
      patients with a recent test. 90-day mortality was highest for patients with a
      recent test taken in an inpatient setting prior to CA-AKI (30.9%). Conclusion:
      Almost half of all patients presenting with CA-AKI are already known to medical
      services, the majority of which have had recent measurement of renal function in
      a hospital setting, suggesting that AKI for at least some of these may
      potentially be predictable and/or avoidable.

PMID- 29025143
TI  - Cost-effectiveness of the pharmacist-assisted warfarin monitoring program at a
      Medical Center in Taiwan.
AB  - Objective: To investigate the cost-effectiveness of the first patient self-paying
      pharmacist-assisted warfarin monitoring (PAWM) program in Taiwan. Design: A
      Markov model with a 1-month cycle length and a 20-year time horizon was employed
      in this study. The model is composed of the following eight states: three no
      event states (i.e. 'subtherapeutic,' 'within therapeutic' and 'supratherapeutic'
      states), two serious adverse events (AEs) (i.e. bleeding and thromboembolism),
      two sequelae states and death. The likelihood of events, costs and utilities were
      derived from local databases and literature, if applicable. This study was
      conducted with a payer's perspective and all costs were discounted with a rate of
      3%. Setting: A pharmacist-led clinic. Participants: A hypothetical cohort of 10
      000 participants. Intervention(s): PAWM versus usual care. Main outcome
      measure(s): Average quality-adjusted life-years (QALYs) gained and cost
      increments per patient, and incremental cost-effectiveness ratios (ICERs).
      Results: The PAWM program resulted in an average of 0.13 QALYs gained and a cost
      increment of NT$53 850 (US$1683) per patient. As the ICER (NT$410 749 [US$12
      836]) was less than the gross domestic product per capita (NT$631 142 [US$19
      723]), the PAWM was considered to be very cost-effective. The sensitivity
      analyses suggested that our result was robust and that the PAWM program had an
      86% probability of being very cost-effective. Conclusions: Even if the costs
      saved from avoiding AEs were thought to be minimal due to the low-medical
      expenditures in Taiwan, the PAWM program was demonstrated to be economical.
      According to our findings, the policymakers should consider reimbursing such a
      service.

PMID- 29025144
TI  - Synthea: An approach, method, and software mechanism for generating synthetic
      patients and the synthetic electronic health care record.
AB  - Objective: Our objective is to create a source of synthetic electronic health
      records that is readily available; suited to industrial, innovation, research,
      and educational uses; and free of legal, privacy, security, and intellectual
      property restrictions. Materials and Methods: We developed Synthea, an open
      source software package that simulates the lifespans of synthetic patients,
      modeling the 10 most frequent reasons for primary care encounters and the 10
      chronic conditions with the highest morbidity in the United States. Results:
      Synthea adheres to a previously developed conceptual framework, scales via open
      source deployment on the Internet, and may be extended with additional disease
      and treatment modules developed by its user community. One million synthetic
      patient records are now freely available online, encoded in standard formats (eg,
      Health Level-7 [HL7] Fast Healthcare Interoperability Resources [FHIR] and
      Consolidated-Clinical Document Architecture), and accessible through an HL7 FHIR
      application program interface. Discussion: Health care lags other industries in
      information technology, data exchange, and interoperability. The lack of freely
      distributable health records has long hindered innovation in health care.
      Approaches and tools are available to inexpensively generate synthetic health
      records at scale without accidental disclosure risk, lowering current barriers to
      entry for promising early-stage developments. By engaging a growing community of
      users, the synthetic data generated will become increasingly comprehensive,
      detailed, and realistic over time. Conclusion: Synthetic patients can be
      simulated with models of disease progression and corresponding standards of care
      to produce risk-free realistic synthetic health care records at scale.

PMID- 29025145
TI  - Online physician ratings fail to predict actual performance on measures of
      quality, value, and peer review.
AB  - Objective: Patients use online consumer ratings to identify high-performing
      physicians, but it is unclear if ratings are valid measures of clinical
      performance. We sought to determine whether online ratings of specialist
      physicians from 5 platforms predict quality of care, value of care, and peer
      assessed physician performance. Materials and Methods: We conducted an
      observational study of 78 physicians representing 8 medical and surgical
      specialties. We assessed the association of consumer ratings with specialty
      specific performance scores (metrics including adherence to Choosing Wisely
      measures, 30-day readmissions, length of stay, and adjusted cost of care),
      primary care physician peer-review scores, and administrator peer-review scores.
      Results: Across ratings platforms, multivariable models showed no significant
      association between mean consumer ratings and specialty-specific performance
      scores (beta-coefficient range, -0.04, 0.04), primary care physician scores (beta
      coefficient range, -0.01, 0.3), and administrator scores (beta-coefficient range,
      -0.2, 0.1). There was no association between ratings and score subdomains
      addressing quality or value-based care. Among physicians in the lowest quartile
      of specialty-specific performance scores, only 5%-32% had consumer ratings in the
      lowest quartile across platforms. Ratings were consistent across platforms; a
      physician's score on one platform significantly predicted his/her score on
      another in 5 of 10 comparisons. Discussion: Online ratings of specialist
      physicians do not predict objective measures of quality of care or peer
      assessment of clinical performance. Scores are consistent across platforms,
      suggesting that they jointly measure a latent construct that is unrelated to
      performance. Conclusion: Online consumer ratings should not be used in isolation
      to select physicians, given their poor association with clinical performance.

PMID- 29025146
TI  - An imported case of leprosy in a trainee from Indonesia to Japan.

PMID- 29025147
TI  - Differential diagnosis between sarcoidosis and granulomatosis with polyangiitis
      in a patient with leptomeningeal, cavernous sinus and pituitary lesions.

PMID- 29025148
TI  - Type 2 split cord malformation: the 'Martian' sign.

PMID- 29025149
TI  - Segment convolutional neural networks (Seg-CNNs) for classifying relations in
      clinical notes.
AB  - We propose Segment Convolutional Neural Networks (Seg-CNNs) for classifying
      relations from clinical notes. Seg-CNNs use only word-embedding features without
      manual feature engineering. Unlike typical CNN models, relations between 2
      concepts are identified by simultaneously learning separate representations for
      text segments in a sentence: preceding, concept1, middle, concept2, and
      succeeding. We evaluate Seg-CNN on the i2b2/VA relation classification challenge
      dataset. We show that Seg-CNN achieves a state-of-the-art micro-average F-measure
      of 0.742 for overall evaluation, 0.686 for classifying medical problem-treatment
      relations, 0.820 for medical problem-test relations, and 0.702 for medical
      problem-medical problem relations. We demonstrate the benefits of learning
      segment-level representations. We show that medical domain word embeddings help
      improve relation classification. Seg-CNNs can be trained quickly for the i2b2/VA
      dataset on a graphics processing unit (GPU) platform. These results support the
      use of CNNs computed over segments of text for classifying medical relations, as
      they show state-of-the-art performance while requiring no manual feature
      engineering.

PMID- 29025151
TI  - African Americans and Heart Disease.

PMID- 29025150
TI  - Collection and determinants of patient reported outcome measures in haemodialysis
      patients in Scotland.
AB  - Background/Introduction: Patient reported outcome measures (PROMs) can evaluate
      the quality of health in patients with established renal failure. There is
      limited experience of their use within national renal registries. Aim: To
      describe the Scottish Renal Registry's (SRR) experience of collecting PROMS in
      the haemodialysis population and correlate PROMS to demographic and clinical
      parameters. Design: Retrospective observational cross-sectional study. Methods:
      Haemodialysis patients in Scotland were invited to complete the KDQOLTM-36
      questionnaire on the day of the annual SRR census in 2015 and 2016.
      Questionnaires were linked to census demographic and clinical variables. Results:
      In 2016, 738 questionnaires were linked to census data (39% of prevalent
      haemodialysis population). Response rates differed with age (>= 65 years 42%, <
      65 years 36%) [chi2P = 0.006]; duration of renal replacement therapy (<1 year
      46%, >=1 < 5 years 38%, >= 5 years 33%) [chi2P = 0.002] and social class
      (Scottish Index of Multiple Deprivation (SIMD) Class 1 32%, Class 2 41%, Class 3
      40%, Class 4 48%, Class 5 40%) [chi2P < 0.001]. There were significant
      differences in PROMs with age, SIMD quintile and primary renal diagnosis.
      Achieving a urea reduction ratio of >65% and dialysing through arteriovenous
      access were associated with significantly higher PROMs. PROMs were not affected
      by haemoglobin or phosphate concentration. Discussion/Conclusions: Routine
      collection of PROMs is feasible and can identify potentially under-recognized and
      treatable determinants to quality of life. The association between attaining
      recommended standards of care and improved PROMs is striking. Individual and
      population-wide strategies are required to improve PROMs.

PMID- 29025152
TI  - Cervical Myelopathy Secondary to Metallic Irritation of the Dura Mater Following
      Insertion of a Spinal Cord Stimulator in a Patient with Ossification of Posterior
      Longitudinal Ligament.

PMID- 29025153
TI  - Atypical Tietze's Syndrome Misdiagnosed as Atypical Chest Pain: Letter to the
      Editor.

PMID- 29025154
TI  - Hematological alterations in protein malnutrition.
AB  - Protein malnutrition is one of the most serious nutritional problems worldwide,
      affecting 794 million people and costing up to $3.5 trillion annually in the
      global economy. Protein malnutrition primarily affects children, the elderly, and
      hospitalized patients. Different degrees of protein deficiency lead to a broad
      spectrum of signs and symptoms of protein malnutrition, especially in organs in
      which the hematopoietic system is characterized by a high rate of protein
      turnover and, consequently, a high rate of protein renewal and cellular
      proliferation. Here, the current scientific information about protein
      malnutrition and its effects on the hematopoietic process is reviewed. The
      production of hematopoietic cells is described, with special attention given to
      the hematopoietic microenvironment and the development of stem cells. Advances in
      the study of hematopoiesis in protein malnutrition are also summarized. Studies
      of protein malnutrition in vitro, in animal models, and in humans demonstrate
      several alterations that impair hematopoiesis, such as structural changes in the
      extracellular matrix, the hematopoietic stem cell niche, the spleen, the thymus,
      and bone marrow stromal cells; changes in mesenchymal and hematopoietic stem
      cells; increased autophagy; G0/G1 cell-cycle arrest of progenitor hematopoietic
      cells; and functional alterations in leukocytes. Structural and cellular changes
      of the hematopoietic microenvironment in protein malnutrition contribute to bone
      marrow atrophy and nonestablishment of hematopoietic stem cells, resulting in
      impaired homeostasis and an impaired immune response.

PMID- 29025155
TI  - CT appearance of gold thread facelift.

PMID- 29025156
TI  - Risk factors associated with mortality from vascular thromboembolic events in
      patients diagnosed with non-small cell lung cancer: A population-based analysis.
AB  - Background: Lung cancer patients are at increased risk for vascular events
      possibly due to cancer induced hypercoagulation. Aim: The purpose of this study
      was to evaluate risk factors associated with the mortality from vascular
      thromboembolic events in patients diagnosed with non-small cell lung cancer
      (NSCLC). Design: Retrospective population-based analysis. Methods: We used
      Surveillance, Epidemiology, and End Results Program for 2004 - 2013 and evaluated
      199,337 patients with NSCLC. Univariate and multivariate subdistribution hazard
      regression models were used to identify potential risk factors for mortality from
      vascular thromboembolic events. Stratification analysis against clinical stage
      was performed to determine if the severity of the disease influenced the
      identified associations. Results: Multivariate Cox regression analysis
      demonstrated that increased risk of mortality due to vascular thromboembolic
      events was associated with age, black race, non-adenocarcinoma histology,
      surgical treatment alone (all, p < 0.001) and north central region of SEER
      registry (p = 0.003). Female gender (p < 0.001), Asian or Pacific Islander race
      (p = 0.001), multiple co-existing primary cancers and late cancer stages (both, p
      < 0.001) were associated with significantly lower risk of mortality due to
      vascular thromboembolic events. The significant predictors of mortality from the
      vascular thromboembolic event were dependent on the stages of the disease.
      Conclusions: Risk factors associated with mortality from the vascular
      thromboembolic events in NSCLC patients identified in this study can promote
      awareness and may help to identify groups of patients that can benefit from
      antithrombotic prophylaxis measures.

PMID- 29025157
TI  - Chronic Pain After Traumatic Brain Injury: Pathophysiology and Pain Mechanisms.
AB  - Background: Traumatic brain injury refers to a broad range of neurological,
      cognitive, and emotional factors that result from the application of an external
      force to the head. Individuals recovering from traumatic brain injury will
      frequently experience acute and chronic pain. Objective: The objective of this
      paper is to discuss the pathophysiological changes resulting from traumatic brain
      injury and how these may be involved in the development and persistence of pain
      after injury. Methods: We based our review on articles retrieved from the MEDLINE
      database of references and abstracts on life sciences and biomedical topics (1966
      to present) using the search engine PubMed (United States National Library of
      Medicine). The published literature focused on traumatic brain injury and pain.
      Conclusions: This review presents evidence that pain is common after traumatic
      brain injury. However, while there are many potential mechanisms explaining this
      problem such as neuroinflammation, excitotoxicity, and axonal degeneration, we
      have no clear understanding of which of them contribute in individual patients.
      The authors highlight the priorities for research that will expand our knowledge
      and that may lead to the rational design of therapies that both reduce pain and
      provide optimal overall outcomes after traumatic brain injury.

PMID- 29025158
TI  - Cluster randomized trials with a small number of clusters: which analyses should
      be used?
AB  - Background: Cluster randomized trials (CRTs) are increasingly used to assess the
      effectiveness of health interventions. Three main analysis approaches are:
      cluster-level analyses, mixed-models and generalized estimating equations (GEEs).
      Mixed models and GEEs can lead to inflated type I error rates with a small number
      of clusters, and numerous small-sample corrections have been proposed to
      circumvent this problem. However, the impact of these methods on power is still
      unclear. Methods: We performed a simulation study to assess the performance of 12
      analysis approaches for CRTs with a continuous outcome and 40 or fewer clusters.
      These included weighted and unweighted cluster-level analyses, mixed-effects
      models with different degree-of-freedom corrections, and GEEs with and without a
      small-sample correction. We assessed these approaches across different values of
      the intraclass correlation coefficient (ICC), numbers of clusters and variability
      in cluster sizes. Results: Unweighted and variance-weighted cluster-level
      analysis, mixed models with degree-of-freedom corrections, and GEE with a small
      sample correction all maintained the type I error rate at or below 5% across most
      scenarios, whereas uncorrected approaches lead to inflated type I error rates.
      However, these analyses had low power (below 50% in some scenarios) when fewer
      than 20 clusters were randomized, with none reaching the expected 80% power.
      Conclusions: Small-sample corrections or variance-weighted cluster-level analyses
      are recommended for the analysis of continuous outcomes in CRTs with a small
      number of clusters. The use of these corrections should be incorporated into the
      sample size calculation to prevent studies from being underpowered.

PMID- 29025159
TI  - IgG4-related disease and ANCA positivity: an overlap syndrome?

PMID- 29025160
TI  - A corollary to the prudent approach to anticoagulation.

PMID- 29025161
TI  - Generalized finger clubbing reveals the cause of secondary gout.

PMID- 29025162
TI  - Complications of obesity.
AB  - Global obesity rates have increased exponentially in recent decades. People are
      becoming obese younger, morbid obesity is increasing and the full health
      implications are only beginning to be seen. This article discusses the latest
      epidemiological data on obesity in adults and children, and systemically reviews
      the complications associated with the condition.

PMID- 29025164
TI  - Shiitake dermatitis.

PMID- 29025163
TI  - Alcohol consumption in 0.5 million people from 10 diverse regions of China:
      prevalence, patterns and socio-demographic and health-related correlates.

PMID- 29025165
TI  - Impact of an emergency department electronic sepsis surveillance system on
      patient mortality and length of stay.
AB  - Objective: The purpose of this study was to determine whether an electronic
      health record-based sepsis alert system could improve quality of care and
      clinical outcomes for patients with sepsis. Materials and Methods: We performed a
      patient-level interrupted time series study of emergency department patients with
      severe sepsis or septic shock between January 2013 and April 2015. The
      intervention, introduced in February 2014, was a system of interruptive sepsis
      alerts triggered by abnormal vital signs or laboratory results. Primary outcomes
      were length of stay (LOS) and in-hospital mortality; other outcomes included time
      to first lactate and blood cultures prior to antibiotics. We also assessed
      sensitivity, positive predictive value (PPV), and clinician response to the
      alerts. Results: Mean LOS for patients with sepsis decreased from 10.1 to 8.6
      days (P < .001) following alert introduction. In adjusted time series analysis,
      the intervention was associated with a decreased LOS of 16% (95% CI, 5%-25%; P =
      .007, with significance of alpha = 0.006) and no change thereafter (0%; 95% CI, 
      2%, 2%). The sepsis alert system had no effect on mortality or other clinical or
      process measures. The intervention had a sensitivity of 80.4% and a PPV of 14.6%.
      Discussion: Alerting based on simple laboratory and vital sign criteria was
      insufficient to improve sepsis outcomes. Alert fatigue due to the low PPV is
      likely the primary contributor to these results. Conclusion: A more sophisticated
      algorithm for sepsis identification is needed to improve outcomes.

PMID- 29025166
TI  - Is Alzheimer's Disease Associated with Previous Opioid Use?
AB  - Objective: We investigated whether opioid use, duration of use, and cumulative
      dose are associated with an increased risk of Alzheimer's disease (AD). Methods:
      A Finnish nationwide nested case-control study, MEDALZ, included 70,718
      individuals with AD and up to four age-, sex-, and region of residence-matched
      comparison individuals. The cohort included all Finnish persons with a clinically
      verified AD diagnosis during 2005 to 2011; the mean age was 80 years (SD = 7
      years), and 65% were women. Register-based data on opioid purchases (excluding
      codeine) were modeled into drug use periods using the PRE2DUP method. Cumulative
      opioid doses were transformed to total standardized doses (TSDs). We utilized a
      three-year time window between exposure (opioid use) and outcome (AD) to avoid
      reverse causality. Analyses were adjusted for comorbid conditions and drug use.
      Results: Opioid use was not associated with an increased risk of AD (adjusted
      odds ratio [OR] = 1.00, 95% confidence interval [CI] = 0.98-1.03). Neither longer
      duration of use (cumulative use for >365 days: adjusted OR = 1.02, 95% CI = 0.96
      1.08) nor high cumulative doses (>90 TSDs: adjusted OR = 1.02, 95% CI = 0.98
      1.07) of opioids was associated with risk of AD. Conclusions: Although opioid use
      was not associated with an increased risk of AD, further studies should be
      performed to assess the safety of long-term opioid use in terms of other
      cognitive effects.

PMID- 29025167
TI  - Vitamin B 12 deficiency may coexist with endocrine causes of hyperpigmentation.

PMID- 29025168
TI  - [A Model Explaining Infantile Esotropia: Dissociated Strabismus as a Result of
      Sensory Interhemispheric Dissociation and Crossed Dominance in the Brainstem].
AB  - Over 150 million years, modern reptiles, birds and mammals evolved. Predatory
      birds and mammals have eyes on the front of their heads. In these animals,
      binocular correspondence, voluntary eye movements, eye-hand coordination, partial
      decussation at the optic chiasm and cortical interhemispheric pathways could
      develop at the cost of a smaller visual field. The subsequent enlargement of the
      cerebral neocortex and the hemispheric pathways are of central importance in
      binocular vision, sensory fusion and infantile strabismus. To investigate visual
      interhemispheric fibers, tractography was used in subjects with infantile
      esotropia (IE), callosal agenesis and control subjects with normal binocularity.
      In human callosal agenesis, normal binocularity could be explained by a different
      interhemispheric connection. In subjects with infantile esotropia, the analyses
      starting from the primary visual area on one side appeared different from the
      analysis from the other side. The distribution areas are asymmetrical between
      sides. Binocularity and alignment not only rely on correspondence between crossed
      and uncrossed hemi-representations but, in addition the corpus callosum, the most
      important interhemispheric pathway in placental mammals, seems important in the
      development of human binocularity. When correspondence is possible between the
      hemi-representations of the crossed and the uncrossed pathway on both sides of
      the cortex, the uncrossed pathway finds its way via the corpus callosum toward
      the contralateral hemi-representation of the same eye. A vertical midline must
      come out of this process. Meanwhile, however, the other uncrossed pathway strives
      to find the vertical midline of the other eye. Likely, the corpus callosum is
      important during the tuning of the pathways involved in sensory fusion. The
      anterior commissure might be an alternative in callosal agenesis. A failure in
      the offset will result in strabismus and crossed dominance after V1.
      Consequently, the normal binocular development of the brainstem (i.e., the
      superior colliculus), will not take place and latent nystagmus, as well as
      dissociated divergence, may ensue.

PMID- 29025169
TI  - [Acute Bilateral Abducens Nerve Palsy in a 7-Year-Old Boy - Atypical Miller
      Fisher Syndrome].

PMID- 29025170
TI  - [The Motor Development of Children with Infantile Esotropia].
AB  - Background Until now, many studies have investigated the link between motor
      development and visual-spatial abilities in infancy and childhood. Most of these
      studies found evidence that there is such a link in typically developing children
      or children with locomotor delay. Only a few studies have tested the consequences
      of this link in children with abnormal visual development because of infantile
      esotropia. Moreover, little is known about the effects of late surgery on motor
      development. Patients and Methods We assessed the motor abilities of 3- to 7-year
      old children with severe deficits in stereopsis due to infantile esotropia (angle
      >= 12 degrees ) and typically developing children prior to and 12 to 16 months
      after surgery. We used the Movement Assessment Battery for Children (Movement ABC
      2). Results Prior to and one year after surgery, the strabismic children showed
      significantly lower global motor scores than normal children. Moreover, in the
      strabismic children, we found significant differences relative to the healthy
      children in the subscales assessing manual dexterity and balance prior to and
      significant differences in the subscales assessing manual dexterity and ball
      skills after surgery. Overall, the strabismic group did not demonstrate
      improvements in motor development after surgery. However, the children with a
      positive Bagolini striated glass test following surgery performed better in the
      subscale assessing balance than children with a negative Bagolini striated glass
      test. Conclusions Motor skills were poorer in children with infantile esotropia,
      both prior to and following surgery. Moreover, the children with improved
      binocular vision after surgery demonstrated better balance skills. Possible
      explanations and practical implications are discussed.

PMID- 29025171
TI  - [The Impact of Macular Development on Full-field and Multifocal ERG in Extremely
      Preterm-born Children with and without Acute Retinopathy of Prematurity].
AB  - Introduction Retinal development is a complex process that can continue into
      early childhood and beyond. Prematurity can affect the maturation of the central
      retina, characterised by a flatter foveal pit and overlying inner retinal layers
      (IRL), leading to a disturbed ratio of outer retinal layers to IRL ("macular
      developmental arrest": MDA) and functional impairment (Bowl et al. 2016 18). The
      purpose of this study was to correlate functional results by electrophysiology
      with the morphological appearance of the fovea in children with spontaneously
      regressed and without ROP and term-born age-matched controls. Methods We
      investigated n = 60 preterm-born children with spontaneously regressed (srROP, n
      = 15) and without ROP (noROP, n = 50) as part of an extensive prospective cohort
      study and compared them to n = 10 term-born age-matched controls (Term). Full
      field electroretinogram (ffERG) and multifocal ERG (mfERG) based on ISCEV
      standards were performed in every child for functional evaluation. Foveal
      morphology was evaluated with optical coherence tomography (SD-OCT, Spectralis,
      Heidelberg Engineering, Germany). Results Analysis of the scotopic ffERG showed
      significantly modified b-wave amplitudes in srROP and noROP, especially when MDA
      was found on SD-OCT. The mfERG exhibited a modified P1-component of the central
      hexagon and the second concentric ring in children with MDA. No other parameters
      were significantly changed. Conclusions Electrophysiological changes can be found
      in extremely preterm-born children, especially with OCT-confirmed foveal
      maturation impairment (MDA), namely in children with spontaneously regressed ROP
      as well as in children without ROP. The reduced b-wave in the scotopic ffERG and
      the reduced P1-component in the mfERG indicate involvement of bipolar cells in
      extremely prematurely born children with MDA. In particular, the correlation of
      MDA with ffERG could be a sign of more global retinal maturation disturbance
      accompanying MDA, and this is seen even without acute ROP.

PMID- 29025172
TI  - [Anti-Myelin Oligodendrocyte Glycoprotein Antibodies in Paediatric Patients with
      Optic Neuritis].
AB  - Background Myelin oligodendrocyte glycoprotein (MOG) is located on the surface of
      oligodendrocytes and myelin in the central nervous system. MOG-IgG is associated
      with acute disseminated encephalomyelitis (ADEM), relapsing and bilateral optic
      neuritis (NNO), and transverse myelitis (TM) in both paediatric and adult
      patients. The combination of NNO and TM or other inflammatory brain lesions is a
      typical feature of neuromyelitis optica spectrum disorders (NMO-SD) which are
      associated with specific pathogenic autoantibodies against the water channel
      aquaporin-4 (AQP4-IgG). However, children with NMO-SD are often seronegative for
      AQP4-IgG but seropositive for MOG-IgG. Therefore, the course and therapy of MOG
      IgG positive NNO in children were of special interest. Patients The course of
      disease of two male patients with acute NNO is presented (bilateral NNO, age of
      onset 8 years each, AQP4-IgG negative, MOG-IgG positive). Several relapses of NNO
      occurred in patient 1 with persisting MOG-IgG in spite of immunsuppressive
      therapy. He suffered from increasing optic atrophy, considerable visual loss and
      transient brainstem affection. Patient 2 showed a monophasic course of disease
      with a rapid decline in MOG-IgG titre and only minor asymmetric optic atrophy.
      Conclusions MOG-IgG in children is associated with recurrent NNO and cerebral
      lesions characteristic of ADEM or NMO-SD. High titres of MOG-IgG are observed
      during the acute phase of clinical symptoms. Relapses of NNO lead to increasing
      loss of retinal nerve fibre layer. Diagnostic investigation includes the
      determination of AQP4-IgG and MOG-IgG as well as magnetic resonance imaging (MRI)
      of brain and spinal cord. The therapeutic consequence of this is consistent
      immunsuppressive treatment, starting with intravenous steroids and followed by
      second-line therapy with steroid sparing immunosuppressants, including
      mycophenolate or azathioprine, followed in refractory cases by rituximab. The
      therapeutic effect should be controlled by laboratory tests of MOG-IgG titre.

PMID- 29025173
TI  - [Impact of Near Addition on the Optical Quality of Diffractive Multifocal
      Intraocular Lenses - a Laboratory Study Using an Optical Bench].
AB  - Purpose To analyse the optical quality of diffractive multifocal intraocular
      lenses (IOLs) with different near additions in a laboratory study. Methods We
      analysed the AcrySof(r) IQ ReSTOR(r) + 2.5 D SV25T0 (Alcon Laboratories inc.,
      Fort Worth, USA), the AcrySof(r) IQ ReSTOR(r) + 3.0 D SN6AD1 (Alcon, USA) and the
      TECNIS(r) ZMA00 and ZMB00 (Abbott Medical Optics, USA) with a power of 21D for
      the distance, using the OptiSpheric(r) IOL PRO optical bench (TRIOPTICS, Wedel,
      Germany). The lenses have a similar optical design but different near additions:
      The ReSTOR + 2.5 D has a near addition of + 2.5 D, the ReSTOR + 3.0 D has a near
      addition of + 3.0 D and both TECNIS IOLs have a near addition of + 4.0 D. We
      evaluated the modulation transfer function area (MTFA) and the Strehl ratio.
      Additionally the optical qualities of the IOL were compared using USAF (United
      States Air Force)-Target pictures. Results The MTFA at the far focus (ReSTOR +
      2.5 D/ReSTOR + 3.0 D/TECNIS) was 47.85/42.06/33.57. The MTFA was 11.05/9.54/8.60
      for intermediate distances. MTFA at the near focus was 20.11/29.50/33.39. The
      Strehl ratio was 0.48/0.42/0.29 at the far focus, 0.11/0.10/0.09 at the
      intermediate focus and 0.20/0.30/0.34 at the near focus. The USAF Target pictures
      correlated with these measurements. Conclusion At the near focus, the TECNIS
      ZMA00 and ZMB00 performed the best, while the ReSTOR + 2.5 D performed the worst.
      At the intermediate distance, all IOLs achieved similar results. At the far
      focus, the ReSTOR + 2.5 D performed the best. Surgeons can choose the right IOL
      for the patients' individual needs, because a broad range of near additions in
      diffractive multifocal IOLs is available these days.

PMID- 29025174
TI  - [Change in Therapy of Neovascular Age-Related Macular Degeneration, Diabetic
      Maculopathy and Macular Edema after Retinal Vein Occlusion].
AB  - Background Therapy of neovascular age-related macular degeneration, diabetic
      maculopathy and macular edema after retinal vein occlusion has changed
      fundamentally since the introduction of anti-VEGF therapy more than 10 years ago.
      With the technological progress in ocular coherence tomography (OCT) functional
      criteria have been replaced by more morphological criteria. Contract law and
      administrative problems have been improved but not solved totally.
      Patients/Materials and Methods In a retrospective study, 207 eyes of 157 patients
      who presented between January 2007 and October 2013 with neovascular age-related
      macular degeneration, diabetic maculopathy or macular edema after retinal vein
      occlusion were analyzed. Baseline visual acuity (VA) was 0.25 (median). Results
      After initial anti-VEGF upload, there was a significant increase in VA from 0.25
      to 0.32 (p < 0.001). Patients with bad VA profited most (p = 0.004). Patients
      with more intravitreal injections had a larger increase in VA (p = 0.002). In the
      mainly VA-controlled group of the first years, VA decreased to 0.05 after one
      year and 3.49 intravitreal injections in the mean. In the OCT-controlled group of
      the later years, the initial increase in VA could be held after one year and 5.03
      intravitreal anti-VEGF applications in the mean. There was a significant
      difference in the course of VA between the two groups (p = 0.001). Mean interval
      between indication and start of therapy was 25.34 days in the early years, and
      5.40 days in the later years. Conclusion Mainly VA-based criteria in the anti
      VEGF therapy of the early years seem to be inferior to morphological criteria of
      the later years. Contract law and administrative problems have delayed the time
      between indication and start of therapy and, thereby, contributed to undersupply
      and worsening functional results.

PMID- 29025175
TI  - [Multifocal Electroretinography in Patients with Poppers Maculopathy].
AB  - Background Maculopathy is a potential side effect of amyl nitrite or "poppers"
      abuse. It is characterized by a sudden, painless decrease in visual acuity. While
      the funduscopic changes are subtle, optical coherence tomography shows
      alterations of the outer retinal layers in the fovea. However, the extent of
      retinal dysfunction remains poorly understood. Materials/Methods We compared the
      multifocal electroretinogram of 6 patients with poppers maculopathy to that of a
      control group consisting of 6 healthy subjects. Response densities and implicit
      times of N1 and P1 were analyzed. Results Response densities and implicit times
      of both N1 and P1 were lower in the patients with poppers maculopathy than in the
      control group, particularly in ring 1 and rings 4 and 5. The only statistically
      significant finding, however, was a reduced N1 response density of one hexagon in
      the patient group. No significant differences were found considering the sum
      response or the averaged rings 1 to 5. Conclusion Compared to a healthy control
      group, the multifocal electroretinogram of patients with poppers maculopathy
      shows no relevant impairment. This contrasts the marked effect of the disease on
      visual acuity. In clinical practice, poppers maculopathy cannot be diagnosed by
      multifocal electroretinography.

PMID- 29025176
TI  - [Real-life Evidence on Treatment Outcomes of Neovascular Age-related Macular
      Degeneration in Germany].
AB  - Treatment of neovascular age-related macular degeneration (AMD) with anti
      vascular endothelial growth factor agents has been improved since its
      introduction in Germany. Several observational studies have demonstrated an
      increased frequency of injections in parallel with improved visual outcomes
      during the first year of treatment over the last 7 years. These results are
      reflected in several case series. However, studies with a longer follow-up
      reported that visual function regressed to baseline vision following an initial
      improvement, e.g. during the first three years of treatment. A delay in treatment
      initiation has been reported mainly for rural areas and management models
      involving more than one ophthalmologist or institution. Encouragingly, recent
      data confirm a positive trend towards reducing treatment delay, increasing
      injection frequency and improving treatment outcomes. Still, further improvements
      are needed to attain optimal treatment outcomes achievable under routine clinical
      conditions in Germany.

PMID- 29025177
TI  - [The recommendations of the S2k guideline for the diagnosis, therapy and
      metaphylaxis of urolithiasis provide a safe course of action for
      ureterorenoscopic stone treatment - results of the BUSTER study].
AB  - BACKGROUND:  Given the high incidence, prevalence and rate of recurrence,
      urolithiasis stone treatment at a high stone-free rate should have a low
      complication rate. The German S2k guideline (GS2k-GL) for the diagnostic testing,
      therapy and metaphylaxis of urolithiasis provides recommendations for the first
      and second choice for stone treatment, depending on stone location and size.
      Ureterorenoscopy (URS) is the treatment of first choice for most stones. URS is
      only the second option for renal stones > 20 mm and proximal ureteric stones <=
      10 mm. The objective was to examine the impact of using URS as the stone
      treatment of first or second choice on the endpoints stone-free rate and severity
      of complications. PATIENTS/METHODS:  The multicentric prospective observational
      study "Evaluation of ureteroroscopic stone treatment - results with regard to
      complications, quality of life and the stone-free rate" (BUSTER) standardised
      recorded perioperative data from 307 patients who had undergone ureterorenoscopic
      stone treatment from January to April 2015 at 14 German urological clinics.
      Treatment decisions were not affected by the study protocol. RESULTS:  In the
      univariate analysis, the stone-free rate for ureteric stones was significantly
      higher when URS was the treatment of first choice (OR 2.21, 95 % CI 1.11 - 4.40,
      p = 0.027). After adjustment for age, BMI, ASA score, preoperative ureteral
      stenting, stone location and size, presence of multiple stones, experience of the
      surgeon, acute or elective URS and operating time, the application of URS as
      treatment of first choice had no significant effect on the stone-free rate (OR
      2.048, 95 % CI 0.890 - 4.710, p = 0.092). After adjustment for stone location and
      size as well as ureteral stenting following URS, the application of URS as
      treatment of first choice had no significant influence on the severity of
      complications (OR 1.019, 95 % CI 0.347 to 2.993; p = 0.973). CONCLUSION:  On the
      basis of our data, URS proved to be a safe and effective stone treatment
      procedure regardless of the degree of guideline conformity. Although the stone
      free rate was higher with URS as treatment of first choice, the results of URS as
      treatment of second choice were not significantly worse. The recommendations of
      the GS2k-GL offer a safe guide for ureterorenoscopic stone treatment. The
      tendency for higher stone-free rates in URS as a treatment of first choice should
      be examined in further studies.

PMID- 29025178
TI  - [Reconstructive urethral surgery].
AB  - Urethral strictures are independent of a patient's age and can happen in every
      life period. They are often iatrogenic, resulting from a transurethral surgical
      procedure or traumatic catheterisation. Endoscopic slotting is the surgery of
      choice; although this method is frequently associated with recurrence. Retrograde
      urethrography or cystourethrography continue to play a central role in diagnostic
      evaluation and treatment. There is no standardised procedure regarding the
      surgical technique, perioperative management, and postoperative follow-up.
      Evidence-based recommendations or guidelines do not exist. For a successful
      surgical treatment of the urethra it is important to have an excellent knowledge
      of the urethral and urogenital anatomy. The permanent removal of urethral
      strictures can only be achieved by open reconstructive surgery. Direct end-to-end
      urethroplasty is used, in general, for short bulbar urethral strictures, while
      urethroplasty with oral mucosa is used for longer bulbar and penile strictures.
      Urethral reconstruction using a patient-specific autologous cell transplant with
      MukoCell(r) is an alternative to the conventional transplantation with native
      oral mucosa. Urethral reconstruction should be performed in specialised centres
      with appropriate expertise.

PMID- 29025179
TI  - Hip Imaging.

PMID- 29025180
TI  - Intra-articular Lesions: Imaging and Surgical Correlation.

PMID- 29025182
TI  - Update on Femoroacetabular Impingement: What Is New, and How Should We Assess It?

PMID- 29025181
TI  - Hip Imaging: Normal Variants and Asymptomatic Findings.

PMID- 29025183
TI  - Postoperative Imaging after Impingement Surgery.

PMID- 29025184
TI  - Greater Trochanteric Pain Syndrome: Abductors, External Rotators.

PMID- 29025185
TI  - Current Concepts in Extra-articular Impingement of the Hip: Clinical Diagnosis,
      Imaging, and Treatment.

PMID- 29025186
TI  - Update on Pediatric Hip Imaging.

PMID- 29025187
TI  - Ultrasound of the Hip Joint, Soft Tissues, and Nerves.

PMID- 29025188
TI  - Inflammatory Conditions of the Hip.

PMID- 29025189
TI  - Leaps in Technology: Advanced MR Imaging after Total Hip Arthroplasty.

PMID- 29025190
TI  - Advanced MR Imaging after Total Hip Arthroplasty: The Clinical Impact.

PMID- 29025191
TI  - ESSR Consensus Document for Detection, Characterization, and Referral Pathway for
      Tumors and Tumorlike Lesions of Bone.

PMID- 29025192
TI  - Erratum: Advanced MRI Techniques for Muscle Imaging.

PMID- 29025193
TI  - Erratum: Emergency and Trauma of the Elbow.

PMID- 29025195
TI  - Chromosomal and subchromosomal anomalies associated to small for gestational age
      fetuses with no additional structural anomalies.
AB  - OBJECTIVES: To assess the chromosomal and subchromosomal anomalies in small for
      gestational age (SGA) fetuses with no additional structural anomalies and their
      clinical outcomes. METHODS: This study retrospectively reviewed the 128 SGA
      fetuses with no additional anomalies and underwent genetic testing with
      karyotyping and chromosomal microarray analysis (CMA). Stratified analysis was
      performed according to the existence of maternal risk factors for SGA (yes or
      no), gestational age at onset (before or after 32 weeks), presence of
      oligohydraminos (yes or no), and umbilical artery Doppler flow (normal or
      abnormal). RESULTS: Chromosomal anomalies were identified in 6 (4.7%) SGA fetuses
      and pathogenic subchromosomal anomalies in 4 (3.1%) by microarray analysis.
      Chromosomal and subchromosomal anomalies were more frequently observed in cases
      with oligohydraminos (P = .017) and with early-onset SGA (P = .042). No
      differences were observed in relation to the existence of maternal risk factors
      and abnormal umbilical artery Doppler flow. Overall survival rate was 75.0% with
      different rates in the early and the late onset group (P < .001). CONCLUSIONS:
      There is a 3.3% incremental yield of subchromosomal anomalies in CMA above
      karyotyping in SGA fetuses. Chromosomal microarray analysis is recommended in SGA
      fetuses with no additional structural anomalies, especially coexisting with
      oligohydraminos and being early onset.

PMID- 29025194
TI  - Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract
      infections.
AB  - BACKGROUND: Acute respiratory infections (ARIs) comprise of a large and
      heterogeneous group of infections including bacterial, viral, and other
      aetiologies. In recent years, procalcitonin (PCT), a blood marker for bacterial
      infections, has emerged as a promising tool to improve decisions about antibiotic
      therapy (PCT-guided antibiotic therapy). Several randomised controlled trials
      (RCTs) have demonstrated the feasibility of using procalcitonin for starting and
      stopping antibiotics in different patient populations with ARIs and different
      settings ranging from primary care settings to emergency departments, hospital
      wards, and intensive care units. However, the effect of using procalcitonin on
      clinical outcomes is unclear. This is an update of a Cochrane review and
      individual participant data meta-analysis first published in 2012 designed to
      look at the safety of PCT-guided antibiotic stewardship. OBJECTIVES: The aim of
      this systematic review based on individual participant data was to assess the
      safety and efficacy of using procalcitonin for starting or stopping antibiotics
      over a large range of patients with varying severity of ARIs and from different
      clinical settings. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory
      Infections Group's Specialised Register, MEDLINE, and Embase, in February 2017,
      to identify suitable trials. We also searched ClinicalTrials.gov to identify
      ongoing trials in April 2017. SELECTION CRITERIA: We included RCTs of adult
      participants with ARIs who received an antibiotic treatment either based on a
      procalcitonin algorithm (PCT-guided antibiotic stewardship algorithm) or usual
      care. We excluded trials if they focused exclusively on children or used
      procalcitonin for a purpose other than to guide initiation and duration of
      antibiotic treatment. DATA COLLECTION AND ANALYSIS: Two teams of review authors
      independently evaluated the methodology and extracted data from primary studies.
      The primary endpoints were all-cause mortality and treatment failure at 30 days,
      for which definitions were harmonised among trials. Secondary endpoints were
      antibiotic use, antibiotic-related side effects, and length of hospital stay. We
      calculated odds ratios (ORs) and 95% confidence intervals (CIs) using
      multivariable hierarchical logistic regression adjusted for age, gender, and
      clinical diagnosis using a fixed-effect model. The different trials were added as
      random-effects into the model. We conducted sensitivity analyses stratified by
      clinical setting and type of ARI. We also performed an aggregate data meta
      analysis. MAIN RESULTS: From 32 eligible RCTs including 18 new trials for this
      2017 update, we obtained individual participant data from 26 trials including
      6708 participants, which we included in the main individual participant data meta
      analysis. We did not obtain individual participant data for four trials, and two
      trials did not include people with confirmed ARIs. According to GRADE, the
      quality of the evidence was high for the outcomes mortality and antibiotic
      exposure, and quality was moderate for the outcomes treatment failure and
      antibiotic-related side effects.Primary endpoints: there were 286 deaths in 3336
      procalcitonin-guided participants (8.6%) compared to 336 in 3372 controls
      (10.0%), resulting in a significantly lower mortality associated with
      procalcitonin-guided therapy (adjusted OR 0.83, 95% CI 0.70 to 0.99, P = 0.037).
      We could not estimate mortality in primary care trials because only one death was
      reported in a control group participant. Treatment failure was not significantly
      lower in procalcitonin-guided participants (23.0% versus 24.9% in the control
      group, adjusted OR 0.90, 95% CI 0.80 to 1.01, P = 0.068). Results were similar
      among subgroups by clinical setting and type of respiratory infection, with no
      evidence for effect modification (P for interaction > 0.05). Secondary endpoints:
      procalcitonin guidance was associated with a 2.4-day reduction in antibiotic
      exposure (5.7 versus 8.1 days, 95% CI -2.71 to -2.15, P < 0.001) and lower risk
      of antibiotic-related side effects (16.3% versus 22.1%, adjusted OR 0.68, 95% CI
      0.57 to 0.82, P < 0.001). Length of hospital stay and intensive care unit stay
      were similar in both groups. A sensitivity aggregate-data analysis based on all
      32 eligible trials showed similar results. AUTHORS' CONCLUSIONS: This updated
      meta-analysis of individual participant data from 12 countries shows that the use
      of procalcitonin to guide initiation and duration of antibiotic treatment results
      in lower risks of mortality, lower antibiotic consumption, and lower risk for
      antibiotic-related side effects. Results were similar for different clinical
      settings and types of ARIs, thus supporting the use of procalcitonin in the
      context of antibiotic stewardship in people with ARIs. Future high-quality
      research is needed to confirm the results in immunosuppressed patients and
      patients with non-respiratory infections.

PMID- 29025196
TI  - Prenatal molecular diagnosis in RASA1-related disease.
AB  - RASA1-related disease is a rare autosomal dominant disease characterized by
      capillary malformations, arteriovenous malformations (AVMs), and/or arteriovenous
      fistulas (AFVs). Penetrance is nearly complete and vascular malformations may
      cause serious complications such as organ injury due to oxygenation disorder,
      brain abscess, hemorrhage, and stroke. Early diagnosis is useful in order to
      discuss optimal management, including AVMs/AVFs embolization or surgical
      procedures, and try to prevent some of the complications. In this context,
      molecular testing of RASA1 gene mutation in relatives may help to better manage
      the family. All arteriovenous malformations are however not accessible to such
      procedures. In addition, these therapeutic procedures may result in potential
      side effects and complications. A couple was referred to our genetics unit and
      asked us for prenatal genetic testing about a RASA1 mutation. Here, we discuss
      about arguments that led our team to accept prenatal testing. To the best of our
      knowledge, no molecular prenatal diagnosis was reported until now in RASA1
      related diseases. This first report of prenatal diagnosis in RASA1-related
      diseases may also offer perspectives for a more general discussion in the field
      of inherited arteriovenous malformations.

PMID- 29025197
TI  - Adenosine versus intravenous calcium channel antagonists for supraventricular
      tachycardia.
AB  - BACKGROUND: People with supraventricular tachycardia (SVT) frequently are
      symptomatic and present to the emergency department for treatment. Although vagal
      manoeuvres may terminate SVT, they often fail, and subsequently adenosine or
      calcium channel antagonists (CCAs) are administered. Both are known to be
      effective, but both have a significant side effect profile. This is an update of
      a Cochrane review previously published in 2006. OBJECTIVES: To review all
      randomised controlled trials (RCTs) that compare effects of adenosine versus CCAs
      in terminating SVT. SEARCH METHODS: We identified studies by searching CENTRAL,
      MEDLINE, Embase, and two trial registers in July 2017. We checked bibliographies
      of identified studies and applied no language restrictions. SELECTION CRITERIA:
      We planned to include all RCTs that compare adenosine versus a CCA for patients
      of any age presenting with SVT. DATA COLLECTION AND ANALYSIS: We used standard
      methodological procedures as expected by Cochrane. Two review authors
      independently checked results of searches to identify relevant studies and
      resolved differences by discussion with a third review author. At least two
      review authors independently assessed each included study and extracted study
      data. We entered extracted data into Review Manager 5. Primary outcomes were rate
      of reversion to sinus rhythm and major adverse effects of adenosine and CCAs.
      Secondary outcomes were rate of recurrence, time to reversion, and minor adverse
      outcomes. We measured outcomes by calculating odds ratios (ORs) and assessed the
      quality of primary outcomes using the GRADE approach through the GRADEproGDT
      website. MAIN RESULTS: We identified two new studies for inclusion in the review
      update; the review now includes seven trials with 622 participants who presented
      to an emergency department with SVT. All included studies were RCTs, but only
      three described the randomisation process, and none had blinded participants,
      personnel, or outcome assessors to the intervention given. Moderate-quality
      evidence shows no differences in the number of people reverting to sinus rhythm
      who were treated with adenosine or CCA (89.7% vs 92.9%; OR 1.51, 95% confidence
      interval (CI) 0.85 to 2.68; participants = 622; studies = 7; I2 = 36%). Low
      quality evidence suggests no appreciable differences in major adverse event rates
      between CCAs and adenosine. Researchers reported only one case of hypotension in
      the CCA group and none in the adenosine group (0.66% vs 0%; OR 3.09, 95% CI 0.12
      to 76.71; participants = 306; studies = 3; I2 = 0%). Included trials did not
      report length of stay in hospital nor patient satisfaction. AUTHORS' CONCLUSIONS:
      Moderate-quality evidence shows no differences in effects of adenosine and
      calcium channel antagonists for treatment of SVT on reverting to sinus rhythm,
      and low-quality evidence suggests no appreciable differences in the incidence of
      hypotension. A study comparing patient experiences and prospectively studied
      adverse events would provide evidence on which treatment is preferable for
      management of SVT.

PMID- 29025198
TI  - Foam dressings for treating pressure ulcers.
AB  - BACKGROUND: Pressure ulcers, also known as pressure injuries and bed sores, are
      localised areas of injury to the skin or underlying tissues, or both. Dressings
      made from a variety of materials, including foam, are used to treat pressure
      ulcers. An evidence-based overview of dressings for pressure ulcers is needed to
      enable informed decision-making on dressing use. This review is part of a suite
      of Cochrane Reviews investigating the use of dressings in the treatment of
      pressure ulcers. Each review will focus on a particular dressing type.
      OBJECTIVES: To assess the clinical and cost effectiveness of foam wound dressings
      for healing pressure ulcers in people with an existing pressure ulcer in any care
      setting. SEARCH METHODS: In February 2017 we searched: the Cochrane Wounds
      Specialised Register; the Cochrane Central Register of Controlled Trials
      (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations);
      Ovid Embase; EBSCO CINAHL Plus and the NHS Economic Evaluation Database (NHS
      EED). We also searched clinical trials registries for ongoing and unpublished
      studies, and scanned reference lists of relevant included studies as well as
      reviews, meta-analyses and health technology reports to identify additional
      studies. There were no restrictions with respect to language, date of publication
      or study setting. SELECTION CRITERIA: Published or unpublished randomised
      controlled trials (RCTs) and cluster-RCTs, that compared the clinical and cost
      effectiveness of foam wound dressings for healing pressure ulcers (Category/Stage
      II or above). DATA COLLECTION AND ANALYSIS: Two review authors independently
      performed study selection, risk of bias and data extraction. A third reviewer
      resolved discrepancies between the review authors. MAIN RESULTS: We included nine
      trials with a total of 483 participants, all of whom were adults (59 years or
      older) with an existing pressure ulcer Category/Stage II or above. All trials had
      two arms, which compared foam dressings with other dressings for treating
      pressure ulcers.The certainty of evidence ranged from low to very low due to
      various combinations of selection, performance, attrition, detection and
      reporting bias, and imprecision due to small sample sizes and wide confidence
      intervals. We had very little confidence in the estimate of effect of included
      studies. Where a foam dressing was compared with another foam dressing, we
      established that the true effect was likely to be substantially less than the
      study's estimated effect.We present data for four comparisons.One trial compared
      a silicone foam dressing with another (hydropolymer) foam dressing (38
      participants), with an eight-week (short-term) follow-up. It was uncertain
      whether alternate types of foam dressing affected the incidence of healed
      pressure ulcers (RR 0.89, 95% CI 0.45 to 1.75) or adverse events (RR 0.37, 95% CI
      0.04 to 3.25), as the certainty of evidence was very low, downgraded for serious
      limitations in study design and very serious imprecision.Four trials with a
      median sample size of 20 participants (230 participants), compared foam dressings
      with hydrocolloid dressings for eight weeks or less (short-term). It was
      uncertain whether foam dressings affected the probability of healing in
      comparison to hydrocolloid dressings over a short follow-up period in three
      trials (RR 0.85, 95% CI 0.54 to 1.34), very low-certainty evidence, downgraded
      for very serious study limitations and serious imprecision. It was uncertain if
      there was a difference in risk of adverse events between groups (RR 0.88, 95% CI
      0.37 to 2.11), very low-certainty evidence, downgraded for serious study
      limitations and very serious imprecision. Reduction in ulcer size, patient
      satisfaction/acceptability, pain and cost effectiveness data were also reported
      but we assessed the evidence as being of very low certainty.One trial (34
      participants), compared foam and hydrogel dressings over an eight-week (short
      term) follow-up. It was uncertain if the foam dressing affected the probability
      of healing (RR 1.00, 95% CI 0.78 to 1.28), time to complete healing (MD 5.67 days
      95% CI -4.03 to 15.37), adverse events (RR 0.33, 95% CI 0.01 to 7.65) or
      reduction in ulcer size (MD 0.30 cm2 per day, 95% CI -0.15 to 0.75), as the
      certainty of the evidence was very low, downgraded for serious study limitations
      and very serious imprecision.The remaining three trials (181 participants)
      compared foam with basic wound contact dressings. Follow-up times ranged from
      short-term (8 weeks or less) to medium-term (8 to 24 weeks). It was uncertain
      whether foam dressings affected the probability of healing compared with basic
      wound contact dressings, in the short term (RR 1.33, 95% CI 0.62 to 2.88) or
      medium term (RR 1.17, 95% CI 0.79 to 1.72), or affected time to complete healing
      in the medium term (MD -35.80 days, 95% CI -56.77 to -14.83), or adverse events
      in the medium term (RR 0.58, 95% CI 0.33 to 1.05). This was due to the very low
      certainty evidence, downgraded for serious to very serious study limitations and
      imprecision. Reduction in ulcer size, patient satisfaction/acceptability, pain
      and cost effectiveness data were also reported but again, we assessed the
      evidence as being of very low certainty.None of the included trials reported
      quality of life or pressure ulcer recurrence. AUTHORS' CONCLUSIONS: It is
      uncertain whether foam dressings are more clinically effective, more acceptable
      to users, or more cost effective compared to alternative dressings in treating
      pressure ulcers. It was difficult to make accurate comparisons between foam
      dressings and other dressings due to the lack of data on reduction of wound size,
      complete wound healing, treatment costs, or insufficient time-frames. Quality of
      life and patient (or carer) acceptability/satisfaction associated with foam
      dressings were not systematically measured in any of the included studies. We
      assessed the certainty of the evidence in the included trials as low to very low.
      Clinicians need to carefully consider the lack of robust evidence in relation to
      the clinical and cost-effectiveness of foam dressings for treating pressure
      ulcers when making treatment decisions, particularly when considering the wound
      management properties that may be offered by each dressing type and the care
      context.

PMID- 29025199
TI  - Effects of growth hormone on glucose metabolism and insulin resistance in human.
AB  - Growth hormone (GH) is important for promotion of somatic growth and the
      regulation of substrate metabolism. Metabolic action of GH occurs in multiple
      tissues including the liver, muscle, fat and pancreas either directly or
      indirectly through insulin-like growth factor 1. The diabetogenic action of GH
      has been well-described in previous in vivo studies. In this paper, we review the
      metabolic effects of GH on peripheral tissues focusing on glucose metabolism and
      insulin resistance, and discuss results from human studies on the long-term
      effects of GH administration on insulin resistance and hyperglycemia.

PMID- 29025200
TI  - Novel genetic cause of idiopathic short stature.
AB  - Traditionally, the growth hormone - insulin-like growth factor I (GH - IGF-I)
      axis is the most important signaling pathway in linear growth, and defects in
      this axis present as growth hormone deficiencies or IGF-I deficiencies. However,
      subtle changes in serum levels of GH or IGF-I, caused by gene mutations involved
      in the GH - IGF-I axis, can present as idiopathic short stature (ISS). This paper
      briefly discusses GHR and IGFALS. In addition, recent studies have shown that
      many factors, including paracrine signals, extracellular matrix, and
      intracellular mechanisms of chondrocytes, regulate the growth plate independent
      of the GH - IGF-I system. Rapid development of diagnostic technologies has
      enabled discovery of many genetic causes of ISS. This paper discusses 5 genes,
      SHOX, NPR2, NPPC, FGFR3, and ACAN, that may lead to better understanding of ISS.

PMID- 29025201
TI  - The triglyceride-to-high density lipoprotein cholesterol ratio in overweight
      Korean children and adolescents.
AB  - PURPOSE: The triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C)
      ratio has recently been reported as a biomarker of cardiometabolic risk in obese
      children and adolescents. The purpose of this study is to describe the TG/HDL-C
      ratio and related factors in overweight and normal weight Korean children and to
      evaluate whether the high TG/HDL-C ratio is associated with insulin resistance in
      overweight children and adolescents. METHODS: Data from 255 overweight (aged
      8.7+/-2.0 years) and 514 normal weight (aged 8.9+/-1.8 years) children and
      adolescents were evaluated. Glucose, insulin, total cholesterol (TC), HDL-C and
      TG levels were measured after overnight fasting, and the TG/HDL-C ratio, non-HDL
      C and the homeostasis model assessment of insulin resistance (HOMA-IR) were
      calculated. RESULTS: The TG/HDL-C ratio was higher in overweight group compared
      to normal weight group (P<0.001). Among overweight children and adolescents,
      alanine aminotransferase (P=0.018), non-HDL-C (P<0.001), and HOMA-IR (P=0.004)
      were different between the TG/HDL-C ratio tertile groups. The prevalence of
      elevated HOMA-IR was increased with increasing TG/HDL-C ratio tertiles (P for
      trend=0.003). On regression analysis adjusted for age and sex, the BMI
      (beta=0.402, P=0.001) and TG/HDL-C ratio (beta=0.251, P=0.014) were independently
      associated with HOMA-IR (adjusted R2=0.324). The TG/HDL-C ratio of 2.0 or more
      showed higher sensitivity (55.6%) and specificity (72.9%), when compared to TC
      (>=200 mg/dL), non-HDL-C (>=145 mg/dL), and LDL-C (>=130 mg/dL) for identifying
      overweight children with elevated HOMA-IR. CONCLUSIONS: The TG/HDL-C ratio is
      independently associated with insulin resistance in overweight children and
      adolescents, and it can be useful in identifying those at higher cardiometabolic
      risk.

PMID- 29025202
TI  - Clinical manifestations of Rathke's cleft cysts and their natural progression
      during 2 years in children and adolescents.
AB  - PURPOSE: Rathke's cleft cyst (RCC) is an asymptomatic benign lesion. With
      increased interest in pediatric endocrinology, the prevalence of RCCs in children
      is also increasing. However, the clinical relevance and proper management of RCC
      is not well defined in children. Therefore, we investigated the clinical
      manifestations and radiologic features of RCC in children and adolescents, as
      well as the natural progression of RCC. METHODS: We retrospectively reviewed the
      medical records of 91 children and adolescents with RCC diagnosed with magnetic
      resonance imaging (MRI) in Severance Children's Hospital from January 2006 to
      December 2015. The clinical, hormonal, and imaging findings were analyzed in
      patient groups classified according to age. The size of each cyst was assessed in
      sixty patients who underwent follow-up MRI during the 2 years. RESULTS: Female
      patients were predominant (64 vs. 27). The common clinical features at
      presentation were endocrine dysfunction (59.3%), headache (23.0%), and dizziness
      (4.4%). Symptoms related to endocrine disorders were more frequent in younger
      patients. In 7 patients managed surgically, the cysts were significantly larger
      and more frequently located in the suprasellar region. Of 60 nonsurgical patients
      with a follow-up MRI performed within 2 years after the diagnosis, the RCC size
      increased in about 26.7% (n=16). CONCLUSIONS: Although 94.4% of the patients with
      RCC had clinical symptoms, surgery was performed in only about 7.5% of patients.
      RCC is associated with pituitary insufficiency, thus, baseline and follow-up
      endocrine function tests are required. Additionally, regular MRI follow-up is
      required in long-term period to monitor change in size.

PMID- 29025203
TI  - Impact of targeted education on managing warning and error signals by children
      and adolescents with type 1 diabetes using the Accu-Chek Combo Insulin Pump
      System.
AB  - PURPOSE: Insulin pumps are widely used in diabetes. They are equipped with safety
      alarms to alert users. Pump manuals contain alarm codes and how to troubleshoot
      them. However, these manuals are lengthy and difficult to use, particularly in
      emergencies. We aim to assess the impact of targeted education on warnings and
      errors in improving competency to troubleshoot the alarms. METHODS: Twenty-one
      patients, with a median age of 13, were recruited over a 5-month period. Each
      patient had 2 study visits. The frequencies and types of alarms were recorded,
      and patients were given a summary sheet that outlined common alarms encountered
      and troubleshooting tips. In visit 2, the frequencies and types of alarms were
      compared to those of visit 1. The patients were asked to fill a questionnaire and
      to rate the education session given in visit 1, their level of competency in
      decrypting alarm codes, and their promptness in responding to alarms. RESULTS:
      Low cartridge (W1), low battery (W2), and bolus cancelled (W8) were the commonest
      warnings. The most noted errors were occlusion (E4), power interruption (E8),
      empty battery (E2), set not primed (E11), and cartridge empty (E1). The numbers
      of warning and error signals markedly decreased after targeted education
      (P<0.05). The ability in decrypting warning signals significantly improved
      (P=0.02), and the frequency of response to pump alarms significantly increased
      (P=0.001). CONCLUSIONS: Certain warnings and errors are more common than others
      in insulin pumps. Targeted education is useful in improving competency and
      response of patients in managing pump alarms.

PMID- 29025204
TI  - Insulin resistance and bone age advancement in girls with central precocious
      puberty.
AB  - PURPOSE: Precocious puberty has significantly increased recently. While obesity
      is associated with puberty timing, the relationship between obesity and central
      precocious puberty (CPP) remains controversial. The purpose of this study was to
      determine whether insulin resistance is associated with bone age (BA) advancement
      in girls with CPP. METHODS: We retrospectively analyzed the records of 804 girls
      referred for puberty evaluation. Anthropometric measurements, BA, sex hormone,
      sex hormone binding globulin (SHBG), and insulin levels, lipid profiles, and
      gonadotropin releasing hormone stimulation tests were assessed. Insulin
      resistance parameters were calculated using the homeostasis model assessment
      insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index
      (QUICKI) models. RESULTS: BA, BA advancement, free estradiol index, insulin, and
      HOMA-IR increased significantly in girls with high body mass index (BMI) compared
      with that of girls with low BMI in cases of CPP. HOMA-IR was positively
      correlated with BA advancement and BMI but negatively correlated with SHBG.
      QUICKI was negatively correlated with BA advancement and BMI and positively
      correlated with SHBG. When HOMA-IR increased by 1, the odds for BA advancement
      increased 120% after adjusting for age and BMI (P=0.033). CONCLUSIONS: Insulin
      resistance could be associated with BA advancement in girls with CPP.

PMID- 29025205
TI  - Diurnal variation of gonadotropin levels in girls with early stages of puberty.
AB  - PURPOSE: Pubertal gonadotropin secretion shows circadian pattern and the
      luteinizing hormone (LH) levels tend to rise in later stages of puberty in girls.
      We studied the usefulness of basal LH in the evaluation of central precocious
      puberty with emphasis on the influence of sampling time. METHODS: Medical records
      of 334 girls that underwent gonadotropin-releasing hormone stimulation test
      (GnRHST) were reviewed. Auxological and laboratory data were compared between
      those with early morning (EM, before 10 AM) and late morning/afternoon (LM/A,
      after 10 AM) basal samples. RESULTS: Among those in sexual maturity rating (SMR)
      2, EM samples showed higher basal LH (P=0.004) compare to LM/A samples, whereas
      those in SMR 3 showed no difference in LH levels between EM and LM/A samples.
      Among girls with pubertal response, EM group showed higher basal LH (P=0.031) and
      follicular stimulating hormone (P=0.008) than LM/A group. The EM basal LH was
      more closely related with the peak stimulated LH than the LM/A basal LH did
      (rs=0.871 vs. rs=0.524). The optimal basal LH cutoffs to predict a pubertal
      response to GnRHST were 0.11 IU/L with a sensitivity of 66.7% and a specificity
      of 78.7% in EM group, and 0.07 IU/L with a sensitivity of 60.0% and a specificity
      of 78.9% in LM/A group, respectively. CONCLUSIONS: In girls with early stages of
      puberty, EM basal LH is a more sensitive screening tool than the LM/A basal LH.
      Diurnal variation should be considered in evaluating children with precocious
      puberty.

PMID- 29025206
TI  - Nonalcoholic fatty liver disease in long-term survivors of childhood-onset
      craniopharyngioma.
AB  - PURPOSE: Hypothalamic obesity in childhood-onset (CO-) craniopharyngioma patients
      may predispose to nonalcoholic fatty liver disease (NAFLD). This study reviewed
      the characteristics of NAFLD associated with CO-craniopharyngioma. METHODS: This
      study retrospectively reviewed 75 patients who underwent surgery for
      craniopharyngioma while younger than 15 years of age between 2000 and 2016.
      RESULTS: Elevated aspartate aminotransferase (AST) or alanine aminotransferase
      (ALT) above 40 IU/L was observed in 51 of the 75 (68%) CO-craniopharyngioma
      patients. Imaging studies were performed in 32 patients with elevated liver
      enzymes. The estimated prevalence of NAFLD in CO-craniopharyngioma was 47%. NAFLD
      was detected in 22 patients (male 59%, 4.3+/-4.0 years after first surgery). The
      mean age at the time of the initial operation was 9.1+/-2.9 years. Six patients
      (27.3%) were diagnosed within 1 year. Among the 19 patients with initial height
      and weight data, the body mass index (BMI) z-score (BMI_Z) at the time of
      diagnosis with NAFLD was 1.37+/-1.01 (range, -0.75 to 3.18), with 4 patients
      (18.2%) being overweight and 9 (40.9%) being obese. BMI_Z increased above BMI_Z
      at the time of the operation in 13 patients (68.4%). The increment in BMI_Z was
      1.13 (range, 0.10-2.84). Seventeen patients did not receive growth hormone. An
      insulin-like growth factor-I level <3rd percentile was observed in 19 patients.
      CONCLUSIONS: NAFLD is common in survivors of CO-craniopharyngioma and may develop
      earlier. If the ALT or AST is above 40 IU/L, a diagnostic work-up should be
      started.

PMID- 29025207
TI  - A rare case of multiple pituitary adenomas in an adolescent Cushing disease
      presenting as a vertebral compression fracture.
AB  - Cushing disease in children and adolescents, especially with multiple pituitary
      adenomas (MPAs), is very rare. We report 17-year-old boy with MPAs. He presented
      with a vertebral compression fracture, weight gain, short stature, headache, and
      hypertension. On magnetic resonance imaging (MRI), only a left pituitary
      microadenoma was found. After surgery, transient clinical improvement was
      observed but headache and hypertension were observed again after 3 months later.
      Follow-up MRI showed a newly developed right pituitary microadenoma 6 months
      after the surgery. The need for careful clinical and radiographic follow-up
      should be emphasized in the search for potential MPAs in patients with persistent
      Cushing disease.

PMID- 29025208
TI  - An atypical case of Noonan syndrome with KRAS mutation diagnosed by targeted
      exome sequencing.
AB  - Noonan syndrome (NS) is a genetic disorder caused by autosomal dominant
      inheritance and is characterized by a distinctive facial appearance, short
      stature, chest deformity, and congenital heart disease. In individuals with NS,
      germline mutations have been identified in several genes involved in the
      RAS/mitogen-activated protein kinase signal transduction pathway. Because of its
      clinical and genetic heterogeneity, the conventional diagnostic protocol with
      Sanger sequencing requires a multistep approach. Therefore, molecular genetic
      diagnosis using targeted exome sequencing (TES) is considered a less expensive
      and faster method, particularly for patients who do not fulfill the clinical
      diagnostic criteria of NS. In this case, the patient showed short stature,
      dysmorphic facial features suggestive of NS, feeding intolerance, cryptorchidism,
      and intellectual disability in early childhood. At the age of 16, the patient
      still showed extreme short stature with delayed puberty and characteristic facial
      features suggestive of NS. Although the patient had no cardiac problems or chest
      wall deformities, which are commonly present in NS and are major concerns for
      patients and clinicians, the patient showed several other characteristic clinical
      features of NS. Considering the possibility of a genetic disorder, including NS,
      a molecular genetic study with TES was performed. With TES analysis, we detected
      a pathogenic variant of c.458A > T in KRAS in this patient with atypical NS
      phenotype and provided appropriate clinical management and genetic counseling.
      The application of TES enables accurate molecular diagnosis of patients with
      nonspecific or atypical features in genetic diseases with several responsible
      genes, such as NS.

PMID- 29025209
TI  - Delayed diagnosis of pituitary stalk interruption syndrome with severe recurrent
      hyponatremia caused by adrenal insufficiency.
AB  - Pituitary stalk interruption syndrome (PSIS) involves the occurrence of a thin or
      absent pituitary stalk, hypoplasia of the adenohypophysis, and ectopic
      neurohypophysis. Diagnosis is confirmed using magnetic resonance imaging.
      Patients with PSIS have a variable degree of pituitary hormone deficiency and a
      wide spectrum of clinical manifestations. The clinical course of the disease in
      our patient is similar to that of a syndrome of inappropriate antidiuretic
      hormone secretion. This is thought to be caused by failure in the suppression of
      vasopressin secretion due to hypocortisolism. To the best of our knowledge, there
      is no case report of a patient with PSIS presenting with hyponatremia as the
      first symptom in Korean children. Herein, we report a patient with PSIS
      presenting severe recurrent hyponatremia as the first symptom, during adolescence
      and explain the pathophysiology of hyponatremia with secondary adrenal
      insufficiency.

PMID- 29025210
TI  - Up-to-date Doppler techniques for breast tumor vascularity: superb microvascular
      imaging and contrast-enhanced ultrasound.
AB  - Ultrasonographic Doppler techniques have improved greatly over the years,
      allowing more sophisticated evaluation of breast tumor vascularity. Superb
      microvascular imaging (SMI) and contrast-enhanced ultrasound (CEUS) with second
      generation contrast agents are two representative up-to-date techniques. SMI is a
      sensitive Doppler technique that adopts an intelligent filter system to separate
      low-flow signals from artifacts. With the development of second-generation
      contrast agents, CEUS has also emerged as a useful Doppler technique for
      evaluating tumor microcirculation. Both techniques can improve the diagnostic
      performance of gray-scale ultrasonography by providing vascular information
      useful not only for the morphologic assessment of microvessels, but also for the
      quantitative analysis of perfusion. In this review, we explain the imaging
      principles and previous research underlying these two vascular techniques, and
      describe our clinical experiences.

PMID- 29025211
TI  - Historical Overview of Stem Cell Biology and Fat Grafting.
AB  - The last two decades have seen significant advances within the field of adipose
      stromal cell transfers, with novel clinical applications being published every
      few months. This article gives a brief historical overview of the development of
      stem cell biology and fat grafting.

PMID- 29025212
TI  - Use of Freshly Isolated Human Adipose Stromal Cells for Clinical Applications.
AB  - The clinical use of adipose-derived cells is being explored very actively around
      the world for various human diseases. Adipose tissue is an abundant tissue source
      that can be easily harvested using liposuction. Human lipoaspirates contain a
      significant amount of mesenchymal stromal cells, as well as other progenitors and
      terminally differentiated cell types. This review covers the isolation of adipose
      stromal vascular fraction (SVF), the quality control and safety analysis of
      freshly isolated cell suspensions. The comparison between freshly isolated
      stromal cells and culture expanded cells from adipose tissue samples is also
      highlighted. This article provides a brief but comprehensive review about SVF
      isolation in the clinical setting, cell characterization, and biological potency
      of freshly obtained adipose stromal cells.

PMID- 29025213
TI  - The Future of Fat Grafting.
AB  - Fat grafting has emerged as an important tool in the armamentarium of plastic
      surgeons. Its applications in aesthetic and reconstructive surgery continue to
      expand. However, its limitations (such as inconsistent survival) remain
      problematic. Recent research efforts have focused on tacking these issues with
      the use of platelet rich plasma, hypoxic preconditioning, hyperbaric oxygen, and
      the tissue engineering of scaffolds. In the future, as these laboratory
      discoveries are translated to clinical application, the beneficial uses of fat
      grafting will continue to increase.

PMID- 29025214
TI  - Effect, Feasibility, and Clinical Relevance of Cell Enrichment in Large Volume
      Fat Grafting: A Systematic Review.
AB  - : Large volume fat grafting is limited by unpredictable volume loss; therefore,
      methods of improving graft retention have been developed. Fat graft enrichment
      with either stromal vascular fraction (SVF) cells or adipose tissue-derived
      stem/stromal cells (ASCs) has been investigated in several animal and human
      studies, and significantly improved graft retention has been reported.
      Improvement of graft retention and the feasibility of these techniques are
      equally important in evaluating the clinical relevance of cell enrichment. We
      conducted a systematic search of PubMed to identify studies on fat graft
      enrichment that used either SVF cells or ASCs, and only studies reporting volume
      assessment were included. A total of 38 articles (15 human and 23 animal) were
      included to investigate the effects of cell enrichment on graft retention as well
      as the feasibility and clinical relevance of cell-enriched fat grafting.
      Improvements in graft retention, the SVF to fat (SVF:fat) ratio, and the ASC
      concentration used for enrichment were emphasized. We proposed an increased
      retention rate greater than 1.5-fold relative to nonenriched grafts and a maximum
      SVF:fat ratio of 1:1 as the thresholds for clinical relevance and feasibility,
      respectively. Nine studies fulfilled these criteria, whereof 6 used ASCs for
      enrichment. We found no convincing evidence of a clinically relevant effect of
      SVF enrichment in humans. ASC enrichment has shown promising results in enhancing
      graft retention, but additional clinical trials are needed to substantiate this
      claim and also determine the optimal concentration of SVF cells/ASCs for
      enrichment. LEVEL OF EVIDENCE: 4.

PMID- 29025215
TI  - Regenerative Cells for the Management of Osteoarthritis and Joint Disorders: A
      Concise Literature Review.
AB  - As the global population ages, the prevalence of osteoarthritis (OA) and joint
      disorders represent a major cause of disability and a significant public health
      burden. As current approaches for the management of OA focus on slowing the
      progression of disease, without repairing the underlying damage, novel treatments
      are necessary to improve outcomes. Over the past decade, autologous cell-based
      therapies using regenerative cells from fat or bone marrow have become a major
      focus of research into new approaches for the treatment of osteoarthritis and
      joint disorders. This review is intended to summarize findings in existing
      literature and identify gaps in knowledge that should be addressed in order to
      advance the field. We acknowledge that some findings may appear inconsistent, but
      show that apparent inconsistency in the literature may be attributable to
      variation in source of cells, stage of disease, method of delivery, follow-up
      time, evaluation method, and a number of other idiosyncrasies of individual
      studies. Still, a number of themes emerge from the data and some broader
      conclusions may be drawn that can be used to guide future studies. Ultimately, we
      conclude that there is overwhelming evidence demonstrating the safety of the
      autologous cell-based therapies. Furthermore, the data support the claim that
      regenerative cells are capable of reversing progression of OA. Regenerative
      cells, and especially those from adipose tissue, represent a promising new
      approach for the treatment of OA. Future work should include appropriate
      controls, and focus on answering questions related to dose required, appropriate
      delivery vehicle, and the impact of multiple treatments. Additionally, future
      studies should look at short and long-term effects of the treatments, and use
      functional as well as radiologic methods to evaluate efficacy.

PMID- 29025216
TI  - Assisted Salvage of Ischemic Fasciocutaneous Flap Using Adipose-Derived
      Mesenchymal Stem Cells: In-Situ Revascularization.
AB  - : Adipose-derived mesenchymal stem cells (ASCs) have been shown to produce
      vascular endothelial growth factor (VEGF) and can increase perfusion in patients
      with critical limb ischemia. We will show that this concept can be applied to
      augment blood flow in zones of flap ischemia. We presented a case study of a 26
      year-old man with a complex hand injury covered by a reverse radial perforator
      fasciocutaneous flap, which developed ischemic necrosis and was treated by
      debridement, transplantation of ASCs to enhance vascular support, and saline
      dressings. ASCs are found in the stromal vascular fraction (SVF), a heterogeneous
      collection of cells, including pericytes and endothelial cells, that is prepared
      from lipoaspirate using collagenase digestion followed by centrifugation. These
      were injected into the flap, the palmar tissues both subjacent and peripheral to
      the flap, and the skin-grafted donor site. The case was documented with
      photography, measurements at hand therapy, and follow-up angiography MRI. At 72
      hours, new vessels appeared diffusely; at 1 week, the remaining tissues of flap
      were bleeding. The wound, 11 cm * 4 cm, contracted spontaneously and was healed
      at 21 days. The skin graft over the donor site demonstrated unusual suppleness
      and elasticity. 3D CT angiography disclosed a new layer of vascularity in the
      superficial tissues of the palm when compared with the normal side. The patient
      regained full composite flexion, pinch, opposition, and wrist extension.
      Application of ASCs into the supporting tissues surrounding the ischemic flap,
      and into the flap itself, constituted a form of in-situ revascularization (ISR)
      that was subjectively and objectively effective for this patient. LEVEL OF
      EVIDENCE: 5.

PMID- 29025217
TI  - Use of Lipotransfer in Scleroderma.
AB  - Lipotransfer for soft tissue filling is a well-established plastic and aesthetic
      surgical technique. Elective fat grafting is considered a safe and well-tolerated
      procedure. Coleman and others have reported that fat grafting may have tissue
      regenerative properties and not only serve as a soft tissue filler. There have
      been reports from our group and others that it may improve fibrosis secondary to
      many different pathological aetiologies including scleroderma, burn injury,
      lichen sclerosis, graft vs host disease, and radiation. The mechanism of action
      remains unclear but has been postulated that is adipose derived stem cells
      (ADSCs) related. Lipoaspirate has been characterised and shown to contain several
      cell populations including fibroblasts, endothelial cells, and ADSCs. The ADSCs
      have shown to secrete angiogenic, immunodulatory, and antiapoptotic factors as
      well as proliferate and differentiate into different cell types similarly to
      other stem cell sources. We have shown that ADSCs are functionally different in
      scleroderma patients but despite this lipotransfer produces a significant
      reversal in the effects of fibrosis in these patients. The advantage of
      lipoaspirate containing a valuable source of regenerative properties, ease of
      access, isolation, and processing may serve a significant future role in the
      treatment of fibrotic conditions.

PMID- 29025218
TI  - Regenerative Cells For Facial Surgery: Biofilling and Biocontouring.
AB  - Zuk et al in 2001 identified stem and regenerative cells within the stromal
      vascular fraction of fat. In preclinical studies, these cells appeared to
      stimulate angiogenesis and reduce inflammation, and soon thereafter, clinical use
      of stromal vascular fraction (SVF) evolved as researchers such as Rigotti,
      Coleman, Mojallal, our group, and others demonstrated that fat can be used for
      both therapeutic and aesthetic indications. The regenerative effects of fat and
      its contents on facial aesthetics have been shown at the histologic and cellular
      level. Regeneration of elastin and collagen fibers as well as improvement in
      capillary density and reduction of inflammation have been reported. We review our
      current approach to the use of regenerative cells and different types of fat
      grafts in facial surgery. The fat graft is classified, both from a regenerative
      point of view as well as a tissue product that can be modified into different
      tissue characteristics, depending on the area and condition treated. Clinical use
      of SVF enriched fat, millifat, microfat, and nanofat grafts as well as composite
      fat grafts are reviewed. Based on clinical experience and evidence to date, it
      appears that the regenerative effects seen with the use of SVF in aesthetic
      surgery are modest, but there appear to be definite histologic findings of
      regeneration. These improvements may not be clinically apparent to a patient when
      cell enriched fat grafts are compared to fat grafts alone. However, the subtle
      changes seen in histology may be cumulative over time. Three types of fat grafts
      are defined: millifat (parcel size 2.4<), microfat (1.2<), and nanofat (400-600
      MUm). Each are characterized by their injectability ratings and emulsification
      parcel size as well as amount of sSVF cells. Newer concepts of periosteal fat
      grafting, buccal fat pad grafting, pyriform aperture fat grafting, intraorbital
      fat grafting, and nanofat grafting are discussed. Composite fat grafts are
      presented as a new concept as is biofilling and biocontouring. The use of
      regenerative cells in facial surgery is evolving rapidly. Our understanding of
      the anatomic changes that occur with aging has become more precise and our
      ability to target histologic changes seen with aging has become more effective.
      Deep fat compartment grafting, superficial fat grafting, nanofat, and SVF are
      becoming important components of contemporary facial rejuvenation. The use of
      regenerative approaches in facial rejuvenation is a logical step in changing the
      paradigm from surgical treatment of aging to a more proactive prevention and
      maintenance approach that keeps up with changes in the tissues as they age.

PMID- 29025219
TI  - Commentary on: New High Dose Pulsed Hyaluronidase Protocol for Hyaluronic Acid
      Filler Vascular Adverse Events.

PMID- 29025220
TI  - Commentary on: Implementation of an Integrated Biodimensional Method of Breast
      Augmentation with Anatomic, Highly Cohesive Silicone Gel Implants: Short-Term
      Results With the First 620 Consecutive Cases.

PMID- 29025221
TI  - Commentary on: Incidence and Preoperative Risk Factors For Major Complications in
      Aesthetic Rhinoplasty: Analysis of 4978 Patients.

PMID- 29025222
TI  - Commentary on: Report on Mortality from Gluteal Fat Grafting: Recommendations
      from the ASERF Task Force.

PMID- 29025223
TI  - Unusual Presentation of Tinea Corporis Associated With the Use of a Microneedling
      Device.

PMID- 29025224
TI  - Acceptable Risk: Who Decides?

PMID- 29025225
TI  - Lymphatic and Sensory Function of the Upper Limb After Brachioplasty in Post
      Bariatric Massive Weight Loss Patients.
AB  - Background: Varied deformities of the upper arm are common after massive weight
      loss. Brachioplasty techniques have been successively modified to improve
      aesthetic outcomes and avoid complications, especially lymphedema and sensory
      damage. Objectives: The authors evaluated lymphatic drainage and sensory function
      of the upper limbs after brachioplasty performed with a double-ellipse marking
      technique, a medial incision, superficial undermining, and posterior arm
      liposuction. Methods: This prospective study included 12 women who underwent
      brachioplasty after bariatric surgery and massive weight loss. Lymphatic drainage
      was evaluated by forearm volumetry and indocyanine green lymphography of the
      entire limb. Cutaneous sensitivity thresholds were determined with Semmes
      Weinstein monofilaments. Results: Patients received postoperative follow up for
      12 months. Complications included a small dehiscence for 1 patient and
      hypertrophic scarring for 2 patients. Cutaneous sensitivity and forearm volumetry
      were unchanged after brachioplasty for all patients. Results of indocyanine green
      lymphography indicated that all patients had normal linear lymphatic patterns pre
      and postoperatively. Conclusions: Results of the study support the belief that
      this type of brachioplasty does not disrupt sensory or lymphatic function of the
      limb. Level of Evidence: 4.

PMID- 29025226
TI  - A Histopathologic Diagnosis of Vascular Occlusion After Injection of Hyaluronic
      Acid Filler: Findings of Intravascular Foreign Body and Skin Necrosis.
AB  - : Before injecting hyaluronic acid (HA) filler into high-risk zones of the face,
      considerable caution must be exercised, including careful selection of the most
      appropriate filler, volume, and injection technique. Rare but severe adverse
      events have occurred during and after injection of HA filler in or around the
      periorbital region, such as skin necrosis and blindness. In the present case,
      involving a 57-year-old woman, approximately 0.1 mL of HA was injected into each
      side of the glabella to minimize wrinkles. The filler was injected into the
      dermis, utilizing the linear threading method. Proper care and caution were
      exercised before and during the procedure. Two days later, purple discoloration
      and erythema were observed in the left glabellar zone and forehead. A biopsy
      specimen was obtained and, based on histopathologic examination, frontal skin
      necrosis secondary to vascular occlusion was diagnosed. The likely cause and
      mechanism of the embolism will be discussed. To the author's knowledge,
      histopathologic findings of an intravascular remnant after injection of HA appear
      to be rare. LEVEL OF EVIDENCE: 5.

PMID- 29025227
TI  - The Efficacy of Vibration Anesthesia on Reducing Pain Levels During Lip
      Augmentation: Worth the Buzz?
AB  - Background: Lip augmentation procedures have increased drastically in the last
      years as patients seek to enhance the shape and size of their lips with dermal
      fillers. One of the main concerns faced with these procedures is the pain
      inflicted through injections. On the other hand, many different techniques have
      been introduced for the reduction of pain while performing office-based minimal
      invasive procedures. Objectives: This study aims to determine the analgesic
      effect of vibration anesthesia during lip augmentation procedures and to evaluate
      its overall effect on the comfort of patients. Methods: A split-lip study was
      designed in a randomized fashion for 25 lip augmentation patients who received
      hyaluronic acid fillers with or without with a concurrent vibration stimulus on
      either half of their lips. Patients were asked to score the pain that they felt
      during lip injections on a scale from 0 to 10 (0 being no pain and 10 being the
      worst pain ever felt) for either lip half. The pain scores were then analyzed for
      significance. Results: The overall pain score on the vibration-assisted side was
      3.82 +/- 1.73 while the pain score for the side with no vibration was 5.6 +/-
      1.76 (P < 0.001). Twenty-three patients (92%) felt less pain with the addition of
      vibration while, interestingly, 2 patients (8%) stated that they felt an increase
      in pain levels on the vibration-treated side. Conclusions: Vibration devices can
      be a safe and effective tool for lowering pain levels in patients undergoing lip
      augmentation with hyaluronic acid fillers. Level of Evidence: 2.

PMID- 29025228
TI  - Commentary on: Patient-Reported Outcomes of Aesthetics and Satisfaction in
      Immediate Breast Reconstruction After Nipple-Sparing Mastectomy With Implants and
      Fat Grafting.

PMID- 29025229
TI  - Mechanical Supplementation With the Stromal Vascular Fraction Yields Improved
      Volume Retention in Facial Lipotransfer: A 1-Year Comparative Study.
AB  - Background: Unpredictable volume maintenance in the long term is a major
      limitation of autologous fat grafting. Objectives: The authors compared results
      of autologous lipotransfer to the face with or without enrichment of fat with the
      stromal vascular fraction (SVF). Methods: Thirty patients with asymmetric
      depletion of facial volume were included in a prospective study. Patients were
      randomly assigned to undergo a single session of autologous fat transfer with
      washed adipose tissue (control group) or with washed adipose tissue combined with
      the pellet of centrifuged lipoaspirate, which contained the SVF (enriched group).
      Patients were evaluated clinically and from photographs. A subset of 5 patients
      in each group underwent computed tomography (CT) preoperatively and 12-months
      postoperatively for quantitative assessment of graft retention. Washed and
      fractionated lipoaspirates were evaluated histochemically and with flow cytometry
      to determine relative abundances of viable cells. Results: No major complications
      occurred. CT findings 12 months postoperatively indicated that patients who
      received SVF-enriched fat had significantly better volume retention (9.6% volume
      loss vs 24% in the control group; P = 0.013). Independent surgeons more
      frequently rated long-term aesthetic outcomes as "excellent" for patients in the
      enriched group (82.5% vs 47.6% for control group). Laboratory results indicated
      that each pellet contained approximately 16,000 intact adipose-derived stem
      cells. Conclusions: Lipotransfer with SVF-enriched adipose tissue is safe and
      associated with improved volume retention, compared with transplantation of
      unenriched fat. The SVF can be dissociated from lipoaspirate by centrifugation to
      yield a large quantity of viable regenerative cells, without enzymatic digestion.
      Level of Evidence: 2.

PMID- 29025230
TI  - Commentary on: Mechanical Supplementation With the Stromal Vascular Fraction
      Yields Improved Volume Retention in Facial Lipotransfer: A 1-Year Comparative
      Study.

PMID- 29025231
TI  - Commentary on: The Efficacy of Vibration Anesthesia on Reducing Pain Levels
      During Lip Augmentation: Worth the Buzz?

PMID- 29025233
TI  - Corrigendum.

PMID- 29025232
TI  - Commentary on: Autologous Adipose-Derived Tissue Matrix Parts I and II.

PMID- 29025234
TI  - Clitoral Surgery After Female Genital Mutilation/Cutting.

PMID- 29025235
TI  - Comments on "Female Genital Mutilation Reconstruction: A Preliminary Report".

PMID- 29025236
TI  - Response to Letters Regarding "Female Genital Mutilation Reconstruction: A
      Preliminary Report".

PMID- 29025237
TI  - The Role of Injectables in Aesthetic Surgery: Financial Implications.
AB  - Background: The plastic surgeon competes with both core and noncore physicians
      and surgeons for traditional cosmetic procedures. In 2007, the American Society
      for Aesthetic Plastic Surgery (ASAPS) and the American Society of Plastic
      Surgeons (ASPS) joined efforts to form a Cosmetic Medicine Task Force to further
      analyze this trend. Objectives: Our objective is to document and quantify the
      patient capture and total collections generated in a single surgeon's practice
      exclusive from Botulinum Toxin A and filler injections over a 10-year period. We
      subsequently identified the effect and importance that fillers and Botulinum
      Toxin A have on an active cosmetic practice. Methods: A retrospective chart
      review of all male and female patients who received Botulinum Toxin A or soft
      tissue filler injections (noninvasive aesthetic treatment) in a single surgeons
      practice from January 2004 to December 2013 was undertaken. Only those patients
      new to the practice and who were exclusively seeking out Botulinum Toxin A or
      fillers were included in the study. Chart review then identified which of these
      selected patients ultimately underwent invasive aesthetic surgery during this 10
      year period. Noninvasive and invasive aesthetic surgery total collections were
      calculated using billing records. Results: From January 2004 to December 2013,
      375 patients entered the senior surgeon's practice specifically requesting and
      receiving noninvasive aesthetic treatments. Of these 375 patients, 59 patients
      (15.7%) subsequently underwent an aesthetic surgery procedure at an average of 19
      months following initial noninvasive aesthetic treatment. Of these 375 patients,
      369 were female and 6 were male. The most common initial invasive aesthetic
      procedure performed after injectable treatment included 22 facelifts (18.5%), 21
      upper eyelid blepharoplasties (17.6%), and 15 endoscopic brow lifts (12.6%).
      Total collections from noninvasive aesthetic sessions and invasive surgery
      combined represented US$762,470 over this 10-year span. This represented
      US$524,771 and US$396,166 in total collections for injectables and surgery
      respectively. Conclusions: Noninvasive aesthetic surgery is a critical part of a
      plastic surgery practice. A measurable and significant number of patients who
      sought out a single plastic surgeon exclusively for noninvasive treatment
      ultimately underwent traditional invasive cosmetic surgical procedures.

PMID- 29025238
TI  - Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL): Why the
      Search for an Infectious Etiology May Be Irrelevant.

PMID- 29025239
TI  - Response to "Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL):
      Why the Search for an Infectious Etiology May Be Irrelevant".

PMID- 29025240
TI  - The Vast Majority of Aesthetic Surgery Patients are at Low Risk for Venous
      Thromboembolism and Do Not Require Chemical Prophylaxis.

PMID- 29025241
TI  - Commentary on: Safety of Cosmetic Surgery in Adolescent Patients.

PMID- 29025242
TI  - The diagnosis and management of congenital and adult-onset hyperinsulinism
      (nesidioblastosis) - literature review.
AB  - Congenital and adult-onset hyperinsulinism (CHI) must be taken under
      consideration in the differential diagnosis of hypoglycaemia symptoms with
      endogenous hyperinsulinism, especially in cases in which there was failure to
      find an insulinoma. Histological examination is necessary for a definitive
      diagnosis. CHI is a disorder with three histopathological variants: focal CHI,
      diffuse CHI, and atypical CHI. These variants are clinically indistinguishable.
      According to published statistics, 0.5 to 5% of nesidioblastosis cases occur in
      adults. Clinical manifestation ranges from mildly symptomatic up to life
      threatening hypoglycaemia. Early diagnosis and treatment are important in young
      and very young patients because early treatment accounts for favourable mental
      outcomes.

PMID- 29025243
TI  - Colon cancer with micropapillary carcinoma component: a clinopathologic study of
      9 cases.
AB  - Recently, colon cancer with micropapillary pattern (MPP) has been identified. MPP
      is defined as tight tufts surrounded by cleft-like space and lacking true
      fibrovascular cores and showing reverse polarity. In this article, we studied
      nine cases of colon cancer with MPP. MPP usually accounted for a minor component
      in total tumour volume, which ranged from 3 to 40% with a mean percentage of
      19.2%. Associated histological subtype showed moderately differentiated tubular
      adenocarcinoma in all cases. The reverse polarity of villin (9/9, diffuse) in MPP
      component was superior to that of CA125 (5/9, focal) or CD10 (5/9, diffuse 2/9,
      focal 3/9). In clinicopathological indicators such as sex, tumour location,
      tumour depth, lymphovascular invasion, lymph node metastasis, or pathological
      stage and clinical behaviour, there was statistically no difference between the
      MPP group and the non-MPP group of the colon. In conclusion, colon cancer with
      MPP is characterised by frequent association with moderately differentiated
      tubular adenocarcinoma as a minor component. Villin immunohistochemistry is
      useful in the detection of reverse polarity of MPP of colon cancer.

PMID- 29025244
TI  - A comparative study of expression of Fc receptors in relation to the autoantibody
      mediated immune response and neutrophil elastase expression in autoimmune
      blistering dermatoses.
AB  - Here we investigated the cutaneous CD32A and CD89 expression in relation to the
      neutrophil elastase (NE) expression and serum level of anti-desmoglein 1 and 3
      (DSG1/DSG3) IgG in pemphigus, anti-BP180/BP230 IgG in bullous pemphigoid (BP),
      anti-gliadin nonapeptides (npG), tissue (tTG), and epidermal transglutaminases
      (eTG) IgA in dermatitis herpetiformis (DH). The examined material consisted of
      skin/mucosal tissues and sera. In total, 87 patients were studied.
      Immunohistochemistry on paraffin-embedded sections with quantitative digital
      morphometry was used to measure the intensity of CD32A/CD89/NE expressions.
      Levels of anti-DSG1/DSG3 IgG, anti-BP180/BP230 IgG, and anti-npG/tTG/eTG IgA were
      evaluated with ELISAs. CD32A was abundantly expressed in cutaneous lesions in
      pemphigus and BP. We found no statistically significant correlation between the
      CD32A/CD89 and NE expression intensities in pemphigus, BP, and DH. There was a
      significant correlation between CD89 expression and anti-npG IgA in DH. Our
      results revealed a lack of correlation between CD32A expressions and anti
      DSG1/DSG3 IgG levels in pemphigus, anti-BP180/BP230 IgG in BP as well as CD89
      expression and anti-tTG/eTG IgA in DH. CD89 seems to be linked with gluten
      intolerance in DH rather than with proteolytic destruction of dermal-epidermal
      junction. CD32A appears to play an important role in mediating skin injury in
      pemphigus and BP, but probably independently from specific autoantibodies.

PMID- 29025245
TI  - Hepatic chemerin mRNA in morbidly obese patients with nonalcoholic fatty liver
      disease.
AB  - The aim of this study was to investigate hepatic chemerin mRNA, serum chemerin
      concentration, and immunohistochemical staining for chemerin and and chemokine
      receptor-like 1 (CMKLR1) in hepatic tissue in 56 morbidly obese women with
      nonalcoholic fatty liver disease (NAFLD) and to search for a relationship with
      metabolic and histopathological features. Chemerin mRNA was assessed by
      quantitative real-time PCR, chemerin, and CMKLR1 immunohistochemical expression
      with specific antibodies, while serum chemerin concentration was assessed with
      commercially available enzyme-linked immunosorbent assays. Serum chemerin
      concentration reached 874.1 +/-234.6 ng/ml. There was no difference in serum
      chemerin levels between patients with BMI < 40 kg/m2 and >= 40 kg/m2. Serum
      chemerin concentration tended to be higher in patients with hepatocyte
      ballooning, greater extent of steatosis, and definite nonalcoholic
      steatohepatitis (NASH). Liver chemerin mRNA was observed in all included patients
      and was markedly, but insignificantly, higher in those with BMI >= 40 kg/m2,
      hepatocyte ballooning, greater extent of steatosis, and definite NASH. Hepatic
      chemerin mRNA might be a predictor of hepatic steatosis, hepatocyte ballooning,
      and NAFLD activity score (NAS) but seemed not to be a primary driver regulating
      liver necroinflammatory activity and fibrosis. The lack of association between
      serum chemerin and hepatic chemerin mRNA may suggest that adipose tissue but not
      the liver is the main source of chemerin in morbidly obese women.

PMID- 29025246
TI  - Vaspin mRNA levels in the liver of morbidly obese women with nonalcoholic fatty
      liver disease.
AB  - The aim of this study was to evaluate hepatic vaspin mRNA in morbidly obese women
      with nonalcoholic fatty liver disease (NAFLD) and to look for its relationships
      with metabolic and histopathological features. The study included 56 severely
      obese women who underwent intraoperative wedge liver biopsy during bariatric
      surgery. Hepatic vaspin mRNA was assessed by quantitative real-time PCR. Vaspin
      mRNA found in all included patients was markedly higher in patients with body
      mass index (BMI) >= 40 kg/m2 (4.59 +/-3.09 vs. 0.44 +/-0.33; p = 0.05). An
      evident but statistically insignificant difference in vaspin mRNA levels was
      observed between patients with and without hepatocyte ballooning (4.77 +/-4.23
      vs. 0.45 +/-0.29, respectively), with and without steatosis (4.80 +/-4.20 vs.
      0.41 +/-0.29, respectively), without and with fibrosis (0.25 +/-0.80 vs. 6.23 +/
      7.2, respectively), and those without and with lobular inflammation (0.27 +/-1.0
      vs. 5.55 +/-10.1, respectively). There was marked difference in vaspin mRNA
      between patients with simple steatosis/borderline nonalcoholic steatohepatitis
      (NASH) compared to those with definite NASH (0.24 +/-0.96 vs. 10.5 +/-10.4).
      Adiposity is an undoubted confounding factor influencing vaspin levels. Hepatic
      vaspin mRNA seems to be markedly elevated in morbidly obese patients with more
      advanced NAFLD and when hallmarks of NASH were observed. Pointing to non-linear
      mRNA levels within the NAFLD spectrum and an evident increase in patients with
      fibrosis and definite NASH, the detrimental action of vaspin cannot be excluded.

PMID- 29025247
TI  - Molecular and histological characteristics of early triploid and partial molar
      pregnancies.
AB  - Molar pregnancy has the highest incidence of all gestational trophoblastic
      diseases. This is a heterogeneous group of diseases, composed of precancerous
      lesions and gestational trophoblastic tumours. The hydatidiform mole is
      characterised by varying degrees of proliferation of syncytiotrophoblastic and
      cytotrophoblastic cells and stromal oedema. Based on established morphological
      and cytogenetic criteria, molar pregnancy is divided into partial and complete.
      The risk of persistent trophoblastic disease is higher in complete moles compared
      with partial moles. The aim of this study was to assess the importance of
      additional molecular methods as a conjunction to the standard histopathological
      analysis to accurately determine the type and origin of triploidy and to detect
      partial molar pregnancy. This study examined a total of 24 cases of triploidy.
      Apart from the detailed histomorphological analysis, a molecular analysis of the
      placental tissue and maternal DNA was also performed. Digynic triploidy was found
      in 15 cases, whereas diandric triploidy was found in nine of the cases. The
      results showed that due to the histomorphological overlap between partial molar
      pregnancy and hydropic abortions, concomitant histopathological analysis of the
      placental tissue and molecular analysis of the placental and maternal DNA can
      lead to correct diagnosis.

PMID- 29025248
TI  - Ultrastructural liver changes in the experimental thyrotoxicosis.
AB  - Aim of the study is to evaluate ultrastructural changes of rat liver in
      experimental thyrotoxicosis. For the study, 36 male rats have been utilized,
      weighing approximately 150-190 g, which were divided into three groups: the
      first, control group (12 animals) was composed of healthy rats that received
      intragastric sodium chloride 0.9% solution, the second group (12 animals) -
      animals with experimental thyrotoxicosis, which received intragastric solution of
      L-thyroxine at the rate of 200 MUg/kg for 2 weeks, and the third group (12
      animals) - rats with experimental thyrotoxicosis, which received intragastric
      solution of L-thyroxine at the rate of 200 MUg/kg for 4 weeks. For electron
      microscopic studies small pieces of liver tissue were taken at the end of the 2nd
      and 4th weeks of the experiment. The material was studied and documented in
      electron micrographs by using a TEM-125K electron microscope. In experiment in
      white male rats the electron-microscopic state of the liver in thyrotoxicosis has
      been studied. It has been established that thyrotoxicosis is accompanied by the
      significant changes of the hepatocytes ultrastructure, blood and bile
      capillaries. Experimental thyrotoxicosis causes significant damage of the liver
      plasma membranes and intracellular structural components of hepatocytes and
      endothelial cells. In experimental thyrotoxicosis, on the background of
      microcirculatory disorders, significant damage of plasmatic and intracellular
      organoid membranes of hepatocytes in the liver develops, which has an adverse
      effect on the functionality of the organ. The found ultrastructural changes are
      aggravated depending on the duration of thyrotoxicosis.

PMID- 29025249
TI  - The utility of glomerular C4d immunostaining in renal biopsies in patients with
      immunoglobulin A nephropathy. A clinicopathological study.
AB  - The course of IgA nephropathy (IgAN) is highly variable and ranges from a totally
      benign condition to end-stage renal disease in approximately one third of cases.
      The identification of new prognostic markers could provide insights into the
      pathogenesis of IgAN and unveil new therapeutic avenues. Glomerular deposition of
      C4d is a marker of activation of the lectin pathway of complement. It is thought
      that activation of the lectin pathway in IgAN is associated with more severe
      renal damage, and more severe histological findings. In view of the above, the
      aim of the present study was to compare the clinical presentation, laboratory
      data, and histological lesions in the renal biopsy in IgAN patients with positive
      and negative staining for mesangial C4d depositions. Our study revealed that
      hypertension, severe proteinuria, a high level of serum creatinine, low eGFR at
      the time of presentation, as well as tubular atrophy/interstitial fibrosis > 50%,
      and endocapillary proliferation were significantly more frequent in the C4d (+)
      group than in the C4d (-) group. Based on our research, we can assume that
      mesangial immunoexpression of C4d seems to be a useful prognostic factor in IgAN.

PMID- 29025250
TI  - Ceramic-polylactide composite material used in a model of healing of osseous
      defects in rabbits.
AB  - The growing demand for various kinds of bone regeneration material has in turn
      increased the desire to find materials with optimal physical, chemical, and
      biological properties. The objective of the present study was to identify the
      proportions of ceramic and polylactide components in a bone substitute material
      prepared in collaboration with the Crystal Chemistry of Drugs Team of the Faculty
      of Chemistry at the Jagiellonian University, which would be optimal for bone
      regeneration processes. Another goal was to provide a histological analysis of
      the influence of a ceramic-polylactide composite on the healing of osseous
      defects in rabbits. The study was performed on laboratory animals (18 New Zealand
      White rabbits). The following study groups were formed: - group A (study group, 9
      animals) - in this group we performed a histological analysis of healing with a
      ceramic-polylactide composite based on an 80/20 mix of hydroxyapatite and
      polylactide; - group B (study group, 9 animals) - in this group we performed a
      histological analysis of healing with a ceramic-polylactide composite with a
      reduced amount of hydroxyapatite compared to the previous group, i.e. in a ratio
      of 61/39; - group K (control, 18 animals) - the control group comprised self
      healing, standardised osseous defects prepared in the calvarial bone of the
      rabbits on the contralateral side. In the assessment of histological samples, we
      were also able to eliminate individual influences that might have led to
      differentiation in wound healing. The material used in the histological analysis
      took the form of rabbit bone tissue samples, containing both defects, with
      margins of around 0.5 cm, taken 1, 3, and 6 months after the experiment. The
      osseous defects from groups A and B filled with ceramic-polylactide material
      healed with less inflammatory infiltration than was the case with control group
      K. They were also characterised by faster regression, and no resorption or
      osteonecrosis, which allowed for better regeneration of the bone tissue. A
      statistical analysis of the study results revealed the increased resorptive
      activity of the composite in group B, which may have been due to its higher
      polylactide content. Simultaneously, we observed that healing of osseous defects
      filled with ceramic-polylactide composites in 80/20 and 61/39 ratios was
      comparable.

PMID- 29025251
TI  - Glial choristoma of the tongue. Clinicopathological analysis of a case and
      pathogenetic insights.
AB  - Glial choristoma of the tongue is a rare developmental anomaly usually occurring
      in the first two years of life. Although diverse theories have been suggested to
      explain its development, they do not seem to take into account the normal tongue
      development. We report here on a glial choristoma of the tongue in a two-month
      old male with the aim to describe the clinicopathological features of this lesion
      and to discuss the pathogenetic role of the cells that normally migrate from the
      cranial neural crests to generate the ectomesenchymal derivatives of the tongue
      and express neuroglial differentiation as normal developmental pathway.

PMID- 29025252
TI  - Solitary breast metastasis from oestrogen receptor-positive pulmonary
      adenocarcinoma: report of a case with a potential pitfall.
AB  - Solitary breast metastases are rare and mimic primary breast carcinoma. A 60-year
      old female with a history of pulmonary adenocarcinoma presented with a solitary
      left breast lump suspicious for malignancy on breast imaging. Core-needle biopsy
      disclosed an adenocarcinoma strongly and diffusely positive for oestrogen
      receptors. Further immunohistochemistry was consistent with the breast tumour
      being a solitary metastasis of her pulmonary cancer. Clinicians and pathologists
      should be aware of the fact that pulmonary adenocarcinomas may sometimes display
      strong rather than only focal positivity for oestrogen receptors by
      immunohistochemistry and may mimic breast cancer of no special type.

PMID- 29025253
TI  - Pathology of mitochondria in MELAS syndrome: an ultrastructural study.
AB  - Ultrastructural changes in skeletal muscle biopsy in a 24-year-old female patient
      with clinically suspected mitochondrial encephalomyopathy lactic acidosis and
      stroke-like episodes (MELAS) syndrome are presented. We observed proliferation
      and/or pleomorphism of mitochondria in skeletal muscle and smooth muscle cells of
      arterioles, as well as in pericytes of capillaries. Paracrystalline inclusions
      were found only in damaged mitochondria of skeletal muscle. Genetic testing
      revealed a point mutation in A3243G tRNALeu(UUR) typical for MELAS syndrome. We
      conclude that differentiated pathological changes of mitochondria in the studied
      types of cells may be associated with the different energy requirements of these
      cells.

PMID- 29025254
TI  - Chromoblastomycosis of the leg.
AB  - CASE REPORT: We herein report a case of chromoblastomycosis presenting as a
      verrucous lesion over the leg. A 56-year-old male patient was a known case of
      carcinoma larynx and was treated for the same. At presentation to our hospital,
      the patient, in addition to the recurrent local disease, was suspected to have
      second primary in the form of verrucous carcinoma of the leg. Histopathological
      examination of the skin biopsy revealed the presence of characteristic pigmented
      sclerotic bodies with pseudoepitheliomatous hyperplasia of the overlying
      epithelium. The case was reported as chromoblastomycosis and the patient
      responded well to anti-fungal chemotherapy in the form of itraconazole.

PMID- 29025256
TI  - Heterometal-Coordinated Monomeric Concanavalin A at pH 7.5 from Canavalia
      ensiformis.
AB  - The structure of concanavalin A (ConA) has been studied intensively owing to its
      specific interactions with carbohydrates and its heterometal (Ca2+ and Mn2+)
      coordination. Most structures from X-ray crystallography have shown ConA as a
      dimer or tetramer, because the complex formation requires specific
      crystallization conditions. Here, we reported the monomeric structure of ConA
      with a resolution of 1.6 A, which revealed that metal coordination could trigger
      sugar-binding ability. The calcium coordination residue, Asn14, changed the
      orientation of carbohydrate-binding residues and biophysical details, including
      structural information, providing valuable clues for the development and
      application of detection kits using ConA.

PMID- 29025257
TI  - Utility of the National Lung Screening Trial Criteria for Estimation of Lung
      Cancer in the Korean Population.
AB  - Purpose: Screening forlung cancerin high-risk patients using theNational Lung
      Screening Trial (NLST) criteria resulted in a decreased lung cancer-related
      mortality rate. However, whether these criteria are applicable to the Korean has
      not been investigated thus far. Therefore, we estimated the utility of the NLST
      criteria as a screening tool for lung cancer in the Korean population. Materials
      and Methods: The total number of newly diagnosed lung cancer cases in 2013 was
      obtained from the Korea National Statistical Office. The proportion of newly
      diagnosed lung cancer cases that met the NLST criteria was calculated via a
      retrospective cohort of a tertiary referral hospital. We estimated the nationwide
      proportion of patients who met the NLST criteria using the 5th Korea National
      Health and Nutrition Examination Survey conducted during 2010-2012 (KNHANES V).
      Results: Using KNHANES V data, we found that approximately 6.92% of the general
      population of Korea would meet the NLST criteria. In the tertiary referral
      hospital, 29.6% of the 2,689 newly diagnosed lung cancer patients met the NLST
      criteria. In 2013, the total number of newly diagnosed lung cancer cases in Korea
      was 23,177. The estimated nationwide proportions of lung cancer patients who met
      and did not meet the NLST criteria were 0.37% and 0.06%, respectively, yielding a
      ratio of 5.78. Conclusion: The NLST criteria demonstrated sound clinical utility
      for lung cancer screening of high-risk patients in Korea.

PMID- 29025258
TI  - MicroRNA-373 Inhibits Cell Proliferation and Invasion via Targeting BRF2 in Human
      Non-small Cell Lung Cancer A549 Cell Line.
AB  - Purpose: The purpose of this study was to investigate the biological role and
      mechanism of miR-373 targeting of TFIIB-related factor 2 (BRF2) in the regulation
      of non-small cell lung cancer (NSCLC) cells. Materials and Methods: miRNA
      microarray chip analysis of four paired NSCLC and adjacent non-tumor tissues was
      performed. Quantitative real-time polymerase chain reaction (qRT-PCR) andwestern
      blotting were used to detect the expression levels of miR-373 and BRF2 in NSCLC
      tissues and cell lines. The dual-luciferase reporter method was performed to
      determine if BRF2 is a target of miR-373. MTT, wound-healing, Transwell, and flow
      cytometric assays were conducted to examine the proliferation, migration,
      invasion, and cell cycle progression of NSCLC A549 cells, respectively; western
      blotting was used to detect the expression of epithelial-mesenchymal transition
      (EMT)-related proteins. Results: The miRNA microarray chip analysis demonstrated
      that miR-373 was down-regulated in NSCLC tissues, and this result was confirmed
      by qRT-PCR. Additionally, miR-373 was confirmed to target BRF2. Moreover, miR-373
      expression was inversely correlated with BRF2 expression in NSCLC tissues and
      cell lines; both miR-373 down-regulation and BRF2 up-regulation were strongly
      associated with the clinicopathological features and prognosis of NSCLC patients.
      In vitro, overexpression of miR-373 markedly inhibited cell proliferation,
      migration, and invasion; up-regulated the expression of E-cadherin; and down
      regulated the expression of N-cadherin and Snail in A549 cell. Knockdown BRF2 by
      siRNA resulted in effects similar to those caused by overexpression of miR-373.
      Conclusion: MiR-373 is decreased in NSCLC, and overexpression of miR-373 can
      suppress cell EMT, and inhibit the proliferation, migration, and invasion of
      NSCLC A549 cells by targeting BRF2.

PMID- 29025259
TI  - Using the capture-recapture method to estimate the human immunodeficiency virus
      positive population.
AB  - OBJECTIVES: The capture-recapture method was applied to estimate the number of
      human immunodeficiency virus (HIV)-positive individuals not registered with any
      data sources. METHODS: This cross-sectional study was conducted in Lorestan
      Province, in the west of Iran, in 2016. Three incomplete sources of HIV-positive
      individuals, with partially overlapping data, were used, including: (a)
      transfusion center, (b) volunteer counseling and testing centers (VCTCs), and (c)
      prison. The 3-source capture-recapture method, using a log-linear model, was
      applied for data analysis. The Akaike information criterion and the Bayesian
      information criterion were used for model selection. RESULTS: Of the 2,456 HIV
      positive patients registered in these 3 data sources, 1,175 (47.8%) were
      identified in transfusion center, 867 (35.3%) in VCTCs, and 414 (16.8%) in
      prison. After the exclusion of duplicate entries, 2,281 HIV-positive patients
      remained. Based on the capture-recapture method, 14,868 (95% confidence interval,
      9,923 to 23,427) HIV-positive individuals were not identified in any of the
      registries. Therefore, the real number of HIV-positive individuals was estimated
      to be 17,149, and the overall completeness of the 3 registries was estimated to
      be around 13.3%. CONCLUSIONS: Based on capture-recapture estimates, a huge number
      of HIV-positive individuals are not registered with any of the provincial data
      sources. This is an urgent message for policymakers who plan and provide health
      care services for HIV-positive patients. Although the capture-recapture method is
      a useful statistical approach for estimating unknown populations, due to the
      assumptions and limitations of the method, the population size may be
      overestimated as it seems possible in our results.

PMID- 29025260
TI  - Microbial Photoelectrotrophic Denitrification as a Sustainable and Efficient Way
      for Reducing Nitrate to Nitrogen.
AB  - Biological removal of nitrate, a highly concerning contaminant, is limited when
      the aqueous environment lacks bioavailable electron donors. In this study, we
      demonstrated, for the first time, that bacteria can directly use the electrons
      originated from the photoelectrochemical process to carry out the
      denitrification. In such photoelectrotrophic denitrification (PEDeN) systems
      (denitrification biocathode coupling with TiO2 photoanode), nitrogen removal was
      verified solely relying on the illumination dosing without consuming additional
      chemical reductant or electric power. Under the UV illumination (30 mW.cm-2,
      wavelength at 380 +/- 20 nm), nitrate reduction in PEDeN apparently followed the
      first-order kinetics with a constant of 0.13 +/- 0.023 h-1. Nitrate was found to
      be almost completely converted to nitrogen gas at the end of batch test. Compared
      to the electrotrophic denitrification systems driven by organics (OEDeN,
      biocathode/acetate consuming bioanode) or electricity (EEDeN, biocathode/abiotic
      anode), the denitrification rate in PEDeN equaled that in OEDeN with a COD/N
      ratio of 9.0 or that in EEDeN with an applied voltage at 2.0 V. This study
      provides a sustainable technical approach for eliminating nitrate from water.
      PEDeN as a novel microbial metabolism may shed further light onto the role of
      sunlight played in the nitrogen cycling in certain semiconductive and conductive
      minerals-enriched aqueous environment.

PMID- 29025262
TI  - Discovery of a Turn-On Fluorescent Probe for Myeloid Cell Leukemia-1 Protein.
AB  - The environment-sensitive probe 2 with turn-on switch for Mcl-1 protein was
      developed herein. After careful evaluation, this small molecule fluorescent probe
      revealed a selective binding affinity with Mcl-1 protein with a Ki value of 2.6
      MUM and can be well applied to imaging Mcl-1 protein or detecting the cellular
      distribution of Mcl-1 protein inhibitors. Compared with other imaging approaches,
      such as the immunofluorescence and fluorescent protein-based techniques, this
      fluorescent method is rapid, convenient, and affordable, especially since a
      washing procedure is no longer needed. This environment-sensitive "off-on" design
      strategy may present a case in point for developing small-molecule fluorescent
      probe of Bcl-2 family proteins.

PMID- 29025261
TI  - Amperometric Gas Sensors as a Low Cost Emerging Technology Platform for Air
      Quality Monitoring Applications: A Review.
AB  - This review examines the use of amperometric electrochemical gas sensors for
      monitoring inorganic gases that affect urban air quality. First, we consider
      amperometric gas sensor technology including its development toward specifically
      designed air quality sensors. We then review recent academic and research
      organizations' studies where this technology has been trialed for air quality
      monitoring applications: early studies showed the potential of electrochemical
      gas sensors when colocated with reference Air Quality Monitoring (AQM) stations.
      Spatially dense networks with fast temporal resolution provide information not
      available from sparse AQMs with longer recording intervals. We review how this
      technology is being offered as commercial urban air quality networks and consider
      the remaining challenges. Sensors must be sensitive, selective, and stable; air
      quality monitors/nodes must be electronically and mechanically well designed.
      Data correction is required and models with differing levels of sophistication
      are being designed. Data analysis and validation is possibly the biggest
      remaining hurdle needed to deliver reliable concentration readings. Finally, this
      review also considers the roles of companies, urban infrastructure requirements,
      and public research in the development of this technology.

PMID- 29025263
TI  - Synthesis of Organophosphorus Compounds through Copper-Catalyzed Annulation
      Involving C-O and C-P Bond Formations.
AB  - A novel copper(II) trifluoromethanesulfonate-catalyzed, high-efficiency, and atom
      economical synthesis of valuable organophosphorus compounds via cascade
      annulation of propargylic alcohols with diphenylphosphine oxide is described.
      This protocol, which has a good functional-group compatibility and insensitivity
      to an ambient atmosphere, provides a simple and direct pathway to the products,
      organophosphorus compounds, in good yields under mild conditions. The method
      could be efficiently scaled up to gram scale, thus highlighting a potential
      application of this methodology.

PMID- 29025264
TI  - B-N-B Bond Embedded Phenalenyl and Its Anions.
AB  - Despite the great potential of heteroatom-containing polycyclic aromatic
      hydrocarbons in organic optoelectronics, there are very limited reports on
      heteroaromatics containing a B-N-B bond in the pi-scaffold. Herein, stable 1,9
      dibora-9a-azaphenalenyl (DBAP) derivatives, named BNB-embedded phenalenyls, are
      presented. The DBAP skeleton contains a three-center two-pi-electron B-N-B moiety
      with 12 pi-electrons and can be regarded as the isoelectronic structure of the
      phenalenyl cation. Chemical reduction of the phenyl derivative of DBAP by
      potassium generated the dianion containing 14 delocalized pi-electrons, which can
      be regarded as the isoelectronic structure of the phenalenyl anion. The dianion
      is sandwiched and stabilized by two bulky [K([18]crown-6)]+ counterions according
      to its X-ray structure. However, its monoanion (an isoelectronic structure of the
      henalenyl radical) generated by mixing equal moles of neutral compound and
      dianion gave an unusual B-N-B-embedded benzo[cd]fluoranthene dianion, which again
      was confirmed by X-ray crystallographic analysis. The new dianion containing 20
      pi-electrons is highly aromatic and is further stabilized by [K([18]crown-6)]+
      counterions. An aromaticity driven rearrangement mechanism was proposed for this
      unusual transformation. Based on X-ray structures and theoretical calculations,
      the B-N-B moiety in the neutral and anionic DBAP participates in the pi-electron
      delocalization along the whole DBAP skeleton like their phenalenyl
      cation/radical/anion counterparts, but with more localized character. Therefore,
      our studies report the first synthesis and characterization of a B-N-B-embedded
      phenalenyl and its anionic species, which show unique electronic structure and
      unusual reactivity different from that of their all-carbon phenalenyl analogues.

PMID- 29025265
TI  - Extending Our Reach for Greater Impact.

PMID- 29025266
TI  - The ABCs of Immunotherapy for Adult Patients With B-Cell Acute Lymphoblastic
      Leukemia.
AB  - OBJECTIVE: To review the pharmacology, efficacy, and safety of Food and Drug
      Administration approved and promising immunotherapy agents used in the treatment
      of acute lymphoblastic leukemia (ALL). DATA SOURCES: A literature search was
      performed of PubMed and MEDLINE databases (1950 to July 2017) and of abstracts
      from the American Society of Hematology and the American Society of Clinical
      Oncology. Searches were performed utilizing the following key terms: rituximab,
      blinatumomab, inotuzumab, ofatumumab, obinutuzumab, Blincyto, Rituxan, Gazyva,
      Arzerra, CAR T-cell, and chimeric antigen receptor (CAR). STUDY SELECTION/DATA
      EXTRACTION: Studies of pharmacology, clinical efficacy, and safety of rituximab,
      ofatumumab, obinutuzumab, inotuzumab, blinatumomab, and CAR T-cells in the
      treatment of adult patients with ALL were identified. DATA SYNTHESIS:
      Conventional chemotherapy has been the mainstay in the treatment of ALL,
      producing cure rates of approximately 90% in pediatrics, but it remains
      suboptimal in adult patients. As such, more effective consolidative modalities
      and novel therapies for relapsed/refractory disease are needed for adult patients
      with ALL. In recent years, anti-CD20 antibodies, blinatumomab, inotuzumab, and
      CD19-targeted CAR T-cells have drastically changed the treatment landscape of B
      cell ALL. CONCLUSION: Outcomes of patients with relapsed disease are improving
      thanks to new therapies such as blinatumomab, inotuzumab, and CAR T-cells.
      Although the efficacy of these therapies is impressive, they are not without
      toxicity, both physical and financial. The optimal sequencing of these therapies
      still remains a question.

PMID- 29025267
TI  - Direct Oral Anticoagulants in Cardioversion: A Review of Current Evidence.
AB  - OBJECTIVE: Direct oral anticoagulants (DOACs) are recommended for the prevention
      of stroke or systemic embolism in nonvalvular atrial fibrillation. Dabigatran,
      rivaroxaban, apixaban, and edoxaban represent possible alternatives to warfarin
      in the setting of cardioversion. A literature review was conducted to evaluate
      the safety and efficacy of DOAC use pericardioversion. DATA SOURCES: A PubMed and
      MEDLINE search through August 2017 was conducted using the following search terms
      alone or in various combinations: dabigatran, rivaroxaban, apixaban, edoxaban,
      betrixaban, DOAC, NOAC, TSOAC, cardioversion. STUDY SELECTION AND DATA
      EXTRACTION: All English-language, human studies comparing the safety and efficacy
      of DOACs with that of other anticoagulants in the setting of cardioversion were
      eligible for inclusion. References from published articles were reviewed for
      additional relevant citations for study inclusion. Four retrospective and 2
      prospective trials comparing DOACs with warfarin were identified. DATA SYNTHESIS:
      The majority of studies included patients undergoing electric cardioversion.
      Based on current evidence, the DOACs perform similarly to warfarin in the
      prevention of stroke and systemic embolism, and bleeding rates are comparable.
      CONCLUSIONS: DOACs may be an attractive alternative to warfarin because of fast
      onset of action, potentially reducing delay to cardioversion. More robust studies
      are needed in patients with renal dysfunction and patients undergoing
      pharmacological cardioversion.

PMID- 29025268
TI  - Understanding persuasive attributes of sports betting advertisements: A conjoint
      analysis of selected elements.
AB  - Background and aims Despite recent growth in sports betting advertising, minimal
      research has examined the influence of different advertising message attributes
      on betting attitudes and behaviors. This study aimed to identify which attributes
      of sports betting advertisements most engage attention, interest, desire and
      likelihood of betting among non-problem, low-risk, moderate-risk, and problem
      gamblers. Methods A novel approach utilizing an experimental design incorporating
      conjoint analysis examined the effects of: three message formats (commentary, on
      screen display, and studio crossover); four appeals (neutral, jovial, ease of
      placing the bet, and sense of urgency); three types of presenters (match
      presenter, sports betting operator, and attractive non-expert female presenter);
      and four bet types (traditional, exotic key event, risk-free, and micro-bet). A
      professional film company using paid actors produced 20 mock television
      advertisements simulating typical gambling messages based on the conjoint
      approach. These were embedded into an online survey of 611 Australian adults.
      Results The most attention-grabbing attributes were type of presenter and type of
      bet. The attractive non-expert female presenter gained more attention from all
      gambler groups than other presenters. The type of bet was most persuasive in
      converting attention into likely betting among all gambler groups, with the risk
      free bet being much more persuasive than other bet types. Problem gamblers were
      distinct by their greater attraction to in-play micro-bets. Discussion and
      conclusion Given the potential for incentivized bets offering financial
      inducements and for in-play micro-bets to undermine harm minimization and
      consumer protection, regulators and wagering operators should reconsider whether
      these bet types are consistent with their responsible gambling objectives.

PMID- 29025269
TI  - Toward a qualitative understanding of binge-watching behaviors: A focus group
      approach.
AB  - Background and aims Binge-watching (i.e., seeing multiple episodes of the same TV
      series in a row) now constitutes a widespread phenomenon. However, little is
      known about the psychological factors underlying this behavior, as reflected by
      the paucity of available studies, most merely focusing on its potential
      harmfulness by applying the classic criteria used for other addictive disorders
      without exploring the uniqueness of binge-watching. This study thus aimed to take
      the opposite approach as a first step toward a genuine understanding of binge
      watching behaviors through a qualitative analysis of the phenomenological
      characteristics of TV series watching. Methods A focus group of regular TV series
      viewers (N = 7) was established to explore a wide range of aspects related to TV
      series watching (e.g., motives, viewing practices, and related behaviors).
      Results A content analysis identified binge-watching features across three
      dimensions: TV series watching motivations, TV series watching engagement, and
      structural characteristics of TV shows. Most participants acknowledged that TV
      series watching can become addictive, but they all agreed having trouble
      recognizing themselves as truly being an "addict." Although obvious connections
      could be established with substance addiction criteria and symptoms, such
      parallelism appeared to be insufficient, as several distinctive facets emerged
      (e.g., positive view, transient overinvolvement, context dependency, and low
      everyday life impact). Discussion and conclusion The research should go beyond
      the classic biomedical and psychological models of addictive behaviors to account
      for binge-watching in order to explore its specificities and generate the first
      steps toward an adequate theoretical rationale for these emerging problematic
      behaviors.

PMID- 29025271
TI  - Psychotropic drugs and CYP2D6 in late-life psychiatric and neurological
      disorders. What do we know?
AB  - INTRODUCTION: Late-life psychiatric and neurological disorders (LLPND) are
      interesting models to understand the potential role of pharmacogenetics in drug
      management, since several pharmacological approaches for treating LLPND have
      proven to be ineffective or deleterious, thus resulting in therapeutic failures
      (TF) and adverse drug reactions (ADR). Common variants in the genes encoding the
      cytochrome P450 (CYP) enzyme system, the 'engine room' of drug metabolism,
      together with well-known age-related increased polypharmacy also contributed to
      the prevalence of TF and ADR observed in these patients, also rising number and
      time of hospital readmissions and rate of institutionalizations. Areas covered:
      The genetics of CYP and how it may be used for the management of the outcomes of
      the most frequent drugs (antidepressants, antipsychotics, anticholinesterase
      inhibitors, and anxiolytics) used in LLPND. Expert opinion: Tailored CYP-based
      pharmacological treatments of LLPND will reduce TFs and ADRs, improving patient's
      life, reducing number and dosage of administered drugs, and the number and
      duration of hospital readmissions, saving costs for clinical management of LLPND.
      Pharmacokinetic interactions are less predictable than pharmacodynamic ones and
      several requests are made to regulatory organisms for the pharmacological
      management of frail older patients affected by LLPND.

PMID- 29025272
TI  - Gankyrin: a novel promising therapeutic target for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is known as fifth common malignancies and third
      common cause of cancer-related death worldwide. The identification of various
      mechanisms which are involved in hepatocarcinogenesis contributes in finding a
      variety of cellular and molecular targets for HCC diagnosis, prevention and
      therapy. Among various identified targets in HCC pathogenesis, Gankyrin is a
      crucial oncoprotein that is up-regulated in HCC and plays a pivotal role in the
      initiation and progression of the HCC. Oncogenic role of Gankyrin has been found
      to stem from inhibition of two ubiquitous tumour suppressor proteins,
      retinoblastoma protein (pRb) and P53, and also modulation of several vital
      cellular signalling pathways including Wnt/beta-Catenin, NF-kappaB, STAT3/Akt, IL
      1beta/IRAK-1 and RhoA/ROCK. As a result, Gankyrin can be considered as a
      potential candidate for diagnosis and treatment of HCC. In this review, we
      summarized the physiological function and the significant role of Gankyrin as an
      important therapeutic target in HCC.

PMID- 29025270
TI  - Design of a randomized clinical trial of a colorectal cancer screening decision
      aid to promote appropriate screening in community-dwelling older adults.
AB  - BACKGROUND: Appropriate colorectal cancer screening in older adults should be
      aligned with the likelihood of net benefit. In general, patient decision aids
      improve knowledge and values clarity, but in older adults, they may also help
      patients identify their individual likelihood of benefit and foster
      individualized decision-making. We report on the design of a randomized clinical
      trial to understand the effects of a patient decision aid on appropriate
      colorectal cancer screening. This report includes a description of the baseline
      characteristics of participants. METHODS: English-speaking primary care patients
      aged 70-84 years who were not currently up to date with screening were recruited
      into a randomized clinical trial comparing a tailored colorectal cancer screening
      decision aid with an attention control. The intervention group received a
      decision aid that included a values clarification exercise and individualized
      decision-making worksheet, while the control group received an educational
      pamphlet on safe driving behaviors. The primary outcome was appropriate screening
      at 6 months based on chart review. We used a composite measure to define
      appropriate screening as screening for participants in good health, a discussion
      about screening for patients in intermediate health, and no screening for
      patients in poor health. Health state was objectively determined using patients'
      Charlson Comorbidity Index score and age. RESULTS: A total of 14 practices in
      central North Carolina participated as part of a practice-based research network.
      In total, 424 patients were recruited to participate and completed a baseline
      visit. Overall, 79% of participants were White and 58% female, with a mean age of
      76.8 years. Patient characteristics between groups were similar by age, gender,
      race, education, insurance coverage, or work status. Overall, 70% had some
      college education or more, 57% were married, and virtually all had Medicare
      insurance (90%). The three primary medical conditions among the cohort were a
      history of diabetes, pneumonia, and cancer (28%, 26%, and 21%, respectively).
      CONCLUSION: We designed a randomized clinical trial to test a novel use of a
      patient decision aid to promote appropriate colorectal cancer screening and have
      recruited a diverse study population that seems similar between the intervention
      and control groups. The study should be able to determine the ability of a
      patient decision aid to increase individualized and appropriate colorectal cancer
      screening.

PMID- 29025274
TI  - Overall survival in patients with glioblastoma before and after bevacizumab
      approval.
AB  - OBJECTIVE: Glioblastoma (GBM) is an aggressive disease with limited therapeutic
      options. While bevacizumab was approved in 2009 for the treatment of patients
      with progressive GBM, its impact on overall survival (OS) remains unclear. Using
      US population-based cancer registry data (SEER), this study compared OS of
      patients diagnosed with GBM before and after bevacizumab approval. METHODS: Adult
      patients from SEER with a GBM diagnosis were divided into two cohorts: patients
      diagnosed in 2006-2008 (pre-bevacizumab cohort, n = 6,120) and patients diagnosed
      in 2010-2012 (post-bevacizumab cohort, n = 6,753). Patients were included
      irrespective of the treatments received. OS post-diagnosis was compared between
      the study cohorts utilizing Kaplan-Meier analyses and multivariate Cox
      proportional hazards regression. RESULTS: Among 12,873 patients with GBM, the
      median age was 62 years, 41% were women, 31% underwent gross total resection, and
      75% received radiation therapy. Survival was stable within the 2006-2008 period
      (median survival = 9 months for each year), but increased after year 2009 (median
      survival = 10 and 11 months for years 2010/2011 and 2012, respectively). The
      adjusted hazard of death was significantly lower in the post-bevacizumab approval
      cohort (hazard ratio = 0.91, p < .01). CONCLUSIONS: The results of this large
      population-based study suggested an improvement in OS among patients with a GBM
      diagnosis in 2010-2012 compared to 2006-2008. While the cause of this improvement
      cannot be proven in a retrospective analysis, the timing of the survival increase
      coincides with the approval of bevacizumab for the treatment of patients with
      progressive GBM, indicating a possible benefit of bevacizumab in this population.

PMID- 29025273
TI  - Higher frequencies of circulating ICOS+, IL-21+ T follicular helper cells and
      plasma cells in patients with new-onset membranous nephropathy.
AB  - BACKGROUND: T follicular helper (TFH) cells and B cells are known to regulate
      humoral immune responses. This study is aimed at examining the putative
      contribution of different subsets of circulating of TFH cells and B cells to
      membranous nephropathy (MN). METHODS: A total of 45 MN patients and 19 healthy
      controls (HCs) were examined for the number of TFH cells and B cells by flow
      cytometry. The level of 24-h urinary protein and eGFR were calculated, and the
      level of serum cytokines was examined. The potential association among these
      measures was analyzed. RESULTS: Compared to the HCs, MN patients had
      significantly higher numbers of circulating CD4+CXCR5+, CD4+CXCR5+ICOS+,
      CD4+CXCR5+CD154+, CD4+CXCR5+IL-21+, and CD4+CXCR5+CD28+ TFH cells, as well as
      IgD+CD27-CD19+ and CD138+CD19+ B cells. However, the number of IgD+CD27+CD19+ B
      cells was significantly lower in MN patients than in the HC. The levels of serum
      IL-21, IL-2, IL-4, IL-10, IL-17A, and IFN-gamma were significantly higher in MN
      patients than in the HC. Furthermore, the numbers of CD4+CXCR5+, CD4+CXCR5+ICOS+,
      CD4+CXCR5+CD154+, CD4+CXCR5+IL-21+, CD4+CXCR5+CD28+ TFH cells, CD138+CD19+ B
      cells, and the level of sera IL-21 were negatively correlated with the values of
      eGFR, but positively correlated with the levels of 24-h urinary proteins.
      Following treatment, the numbers of CD4+CXCR5+, CD4+CXCR5+ICOS+,
      CD4+CXCR5+CD154+, CD4+CXCR5+IL-21+, CD4+CXCR5+CD28+ TFH cells, CD138+CD19+ B
      cells, and the levels of IL-21 were significantly reduced. In contrast, IL-4 and
      IL-10 levels were noticeably increased after treatment. CONCLUSIONS: Data suggest
      that activated TFH and plasma cells may contribute to the pathogenesis of MN.

PMID- 29025276
TI  - Once-Daily Versus Twice-Daily Enoxaparin for the Treatment of Acute Venous
      Thromboembolism in Cancer Patients.
AB  - BACKGROUND: No randomized controlled trials have investigated enoxaparin once
      versus twice daily for venous thromboembolism (VTE) treatment in cancer patients.
      OBJECTIVE: To compare the safety and efficacy of enoxaparin 1 mg/kg twice daily
      versus enoxaparin 1.5 mg/kg/day for the treatment of acute VTE in cancer
      patients. METHODS: This was a single-center, retrospective, observational cohort
      study. Adults with active cancer and an acute VTE were included. The primary
      outcome evaluated was the incidence of clinically relevant (major and nonmajor)
      bleeding (CRB) within 30 days of enoxaparin initiation. Secondary outcomes
      included the incidence of CRB, thrombosis, and death at 30, 90, and 180 days. The
      study protocol was approved by the institutional review board. RESULTS: A total
      of 123 patients met inclusion criteria; 85 patients (69%) were treated with once
      daily and 38 patients (31%) with twice-daily enoxaparin. CRB was numerically
      higher at 30 days in the twice-daily enoxaparin group compared with the once
      daily group (5.3% vs 2.4%, P = 0.587). There was a nonsignificant higher
      incidence of CRB in the once-daily enoxaparin group compared with the twice-daily
      group at 90 days (8.3% vs 8%, P = 1.0) and 180 days (12.5% vs 7.1%, P = 1.0). The
      composite outcome of CRB, thrombosis, and death was higher at all time points
      with enoxaparin once daily. CONCLUSIONS: Lack of statistical power in this study
      precludes definitive conclusions. Clinicians may consider twice-daily enoxaparin
      because of potentially fewer adverse events but may be limited by patient
      preference and/or financial constraints.

PMID- 29025275
TI  - Complementary and Alternative Medicine Use in Minority and Medically Underserved
      Oncology Patients: Assessment and Implications.
AB  - INTRODUCTION: Complementary and alternative medicine (CAM) use in minority and
      medically underserved oncology patients is not well documented. We assessed
      knowledge and utilization of CAM in a sample of these patients receiving
      treatment at an urban community hospital. METHODS: Patients with cancer were
      interviewed using an electronic application that depicted specific CAM therapies.
      Patients were questioned on their knowledge and utilization of therapies,
      deterrents to use, and interest in using these therapies if they were made
      available. RESULTS: Patients (n = 165) reported a high awareness and use of CAM
      therapies. CAM use was highest for prayer (85%), relaxation (54%), special diet
      (29%), meditation (19%), and massage (18%). Patients' interest in using CAM was
      high for nearly all therapies. Lack of adequate knowledge and cost of use were
      reported as deterrents to use. Female patients reported higher use of
      aromatherapy relative to males (37.1% vs 19.4%, P = .02); those with higher
      education reported greater use of relaxation (60.8% vs 28.6%, P = .02); non
      Hispanics reported higher use of relaxation relative to Hispanics (63.5% vs
      44.2%, P = .03), and African American patients reported higher use of relaxation
      relative to White patients (69.2% vs 50%, P = .03). CONCLUSIONS: CAM use in
      minority and medically underserved cancer patients is common, but not
      professionally guided; thus, concerns remain regarding its safe use. Our data
      underscore the importance of patient-physician dialogue regarding CAM use in this
      patient population, and interest in access to the medically guided integration of
      evidence-based CAM therapies.

PMID- 29025278
TI  - Angiogenic Growth Factors for Coronary Artery Disease: Current Status and
      Prospects.
AB  - Although there have been advances in coronary artery bypass grafting and
      percutaneous coronary intervention, some patients who have ischemic coronary
      artery disease (CAD) are ineligible for revascularization due to suboptimal
      anatomy. Cardiac angiogenesis is not only a physiological response to ischemia or
      hypoxia but also a potential target of therapeutic strategies. Preclinical
      studies have shown a great enthusiasm on therapeutic angiogenesis for ischemic
      CAD. However, the latest trials provided the limited evidence on its efficacy.
      This article aims to discuss the physiological process of angiogenesis, the
      characteristic of angiogenic growth factors, delivery system, and clinical and
      preclinical studies, which can provide a novel insight into the therapeutic
      angiogenesis for CAD.

PMID- 29025277
TI  - Clinical Analysis of Recurrence Patterns in Patients With Nasopharyngeal
      Carcinoma Treated With Intensity-Modulated Radiotherapy.
AB  - OBJECTIVE: To evaluate the characteristics and risk factors for locoregional
      recurrence in patients with nasopharyngeal carcinoma (NPC) treated with intensity
      modulated radiotherapy (IMRT). METHODS: The clinical diagnosis and treatment data
      of 195 patients with NPC treated with IMRT from March 2005 to May 2010 (including
      9, 24, 70, and 92 cases of stage I, II, III, and IV disease, respectively,
      according to the 7th edition American Joint Committee on Cancer staging criteria)
      were retrospectively analyzed. The Kaplan-Meier method was used for survival
      analysis, and logistic regression was used to conduct univariate and multivariate
      analyses. RESULTS: The 5-year recurrence rate was 10.8%, and the 5-year local and
      regional recurrence rates were 8.7% and 3.4%, respectively. Multivariate analysis
      showed that the short axis of the cervical lymph nodes (>=3 cm) was an
      influencing factor for regional lymph node recurrence after IMRT. CONCLUSION: In
      field and high-dose region failures were the main patterns associated with local
      regional recurrence, and nasopharyngeal recurrence was most commonly detected.
      Newly diagnosed patients with large cervical lymph nodes (short diameter >=3 cm)
      should be carefully followed up considering regional lymph node recurrence.

PMID- 29025279
TI  - Fixation Techniques in Lower Extremity Syndesmotic Injuries.

PMID- 29025281
TI  - Understanding Treatment Adherence With the Health Belief Model in Children With
      Cystic Fibrosis.
AB  - OBJECTIVE: Children's health beliefs are significantly related to their
      adherence; however, pediatric literature has rarely tested health-related
      theories as a whole. The goal of the present study was to evaluate the use of the
      health belief model (HBM) in understanding children's adherence, both globally
      and to individual treatment components. METHOD: Thirty-three patient-parent dyads
      completed questionnaires regarding health beliefs and adherence to medical
      regimens. RESULTS: Multiple linear regressions found a significant relationship
      among the HBM variables and reports of global adherence for children and parents.
      For children, the HBM variables were significantly related to adherence to
      aerosol medications, aerosol antibiotics, metered dose inhalers, and vitamins.
      For parents, the HBM variables were significantly related to children's adherence
      to airway clearance, oral antibiotics, and vitamins. Paired sample t tests found
      children and parents had significantly discrepant heath beliefs. CONCLUSION:
      These findings provide further support for the HBM in evaluating pediatric
      adherence, with evidence that barriers and cues to action may be targets for
      early intervention. Future research using this model to identify a comprehensive
      way to assess, understand, and elicit change in the adherence to medical regimens
      for youth with chronic illness would be beneficial.

PMID- 29025280
TI  - Effects of prenatal PPAR-gamma agonist rosiglitazone exposure on rat hippocampus
      development in a time-dependent manner: A stereological and histopathological
      study.
AB  - Rosiglitazone is in the thiazolidinedione class of drugs used in the treatment of
      type 2 diabetes mellitus. It works as an insulin sensitizer by binding to the
      peroxisome proliferator-activated receptor gamma. We investigated the effects of
      prenatally administered rosiglitazone on pyramidal cell numbers and morphologies
      in the hippocampus at postnatal period using histochemical and stereological
      techniques, congenital morphological properties and the number of offspring in
      rats. Eighteen female rats were grouped into control (C), low-dose rosiglitazone
      (LDR) and high-dose rosiglitazone (HDR). LDR pregnant rats received 2 mg/kg/day
      of rosiglitazone via oral gavage during the first 16 days of the pregnancy. HDR
      rats received 5 mg/kg/day. The infants were grouped into newborn (NB), 4 week (4
      W) and 12 week (12 W). A side from histopathologic and congenital assessments,
      stereological analyses were performed using the optical fractionator method.
      Congenital anomaly was not detected in any of the rosiglitazone treatment groups,
      and their number of offspring was similar to that of the C group. Stereological
      counts revealed a significant reduction in the number of hippocampal pyramidal
      cells in the C and LDR groups but not in the HDR group until birth to 12th week.
      When NB groups were compared, the number of pyramidal cells in the HDRNB group
      was less than those in the LDRNB and CNB groups. HDR affected apoptosis or the
      proliferation and maturation of progenitor cells to the pyramidal neuron during
      neurodevelopment in the hippocampus, whereas LDR did not adversely affect
      neuronal development and did not cause congenital anomalies.

PMID- 29025282
TI  - Clinical Outcomes Following an Open Gastrocnemius Recession Combined With an
      Endoscopic Plantar Fasciotomy.
AB  - : At present, there is a paucity of literature describing the clinical outcomes
      following a combined gastrocnemius recession and endoscopic plantar fasciotomy.
      The purpose of the present report is to describe our preliminary findings
      following a combined gastrocnemius recession and endoscopic plantar fasciotomy
      for the treatment of plantar fasciitis and gastrocnemius equinus recalcitrant to
      conservative therapy. Twenty-five consecutive ankles in 23 patients (age 51.2 +/-
      12.5 years, 4 men) met the inclusion and exclusion criteria. The average follow
      up was 3.7 months. Compared across time, there were statistically significant
      improvements in pain, t(24) = 7.878, P < .001; dorsiflexion, t(24) = -6.125, P <
      .001; and eversion, t(23) = -3.610, P = .001. Plantar flexion and inversion
      remained similar across time ( P = .722 and P = .268, respectively). No
      statistically significant correlations were found between age and any of the
      postoperative outcome variables ( P >= .056) or body mass index and any of the
      postoperative outcome variables ( P >= .140). The authors believe that an
      isolated plantar fasciotomy alleviates symptoms in the majority of patients. When
      gastrocnemius equinus is also present, however, the authors advocate performing
      an open gastrocnemius recession as well. If the gastrocnemius pathology is not
      addressed, symptoms are likely to persist. The findings of the present report
      confirm the effectiveness of a combined gastrocnemius recession and endoscopic
      plantar fasciotomy to improve pain and range of motion. LEVELS OF EVIDENCE: Case
      series, Level IV: Retrospective.

PMID- 29025283
TI  - Translation, reliability, and clinical utility of the Melbourne Assessment 2.
AB  - OBJECTIVE: The aims were to (i) provide a German translation of the Melbourne
      Assessment 2 (MA2), a quantitative test to measure unilateral upper limb function
      in children with neurological disabilities and (ii) to evaluate its reliability
      and aspects of clinical utility. METHODS: After its translation into German and
      approval of the back translation by the original authors, the MA2 was performed
      and videotaped twice with 30 children with neuromotor disorders. For each
      participant, two raters scored the video of the first test for inter-rater
      reliability. To determine test-retest reliability, one rater additionally scored
      the video of the second test while the other rater repeated the scoring of the
      first video to evaluate intra-rater reliability. Time needed for rater training,
      test administration, and scoring was recorded. RESULTS: The four subscale scores
      showed excellent intra-, inter-rater, and test-retest reliability with intraclass
      correlation coefficients of 0.90-1.00 (95%-confidence intervals 0.78-1.00). Score
      items revealed substantial to almost perfect intra-rater reliability (weighted
      kappa kw = 0.66-1.00) for the more affected side. Score item inter-rater and test
      retest reliability of the same extremity were, with one exception, moderate to
      almost perfect (kw = 0.42-0.97; kw = 0.40-0.89). Furthermore, the MA2 was
      feasible and acceptable for patients and clinicians. CONCLUSIONS: The MA2 showed
      excellent subscale and moderate to almost perfect score item reliability.
      Implications for Rehabilitation There is a lack of high-quality studies about
      psychometric properties of upper limb measurement tools in the neuropediatric
      population. The Melbourne Assessment 2 is a promising tool for reliable
      measurement of unilateral upper limb movement quality in the neuropediatric
      population. The Melbourne Assessment 2 is acceptable and practicable to
      therapists and patients for routine use in clinical care.

PMID- 29025284
TI  - Relationship of Aortic Wall Distensibility to Mitral and Aortic Valve
      Calcification: The Multi-Ethnic Study of Atherosclerosis.
AB  - Data are limited on whether valvular calcification is associated with aortic wall
      stiffness. We tested whether aortic valve calcification (AVC) and/or mitral valve
      calcification (MVC) is inversely associated with aortic distensibility (AD).
      Cross-sectional study conducted in a subset of the Multi-Ethnic Study of
      Atherosclerosis (MESA) included 3676 MESA participants aged 44 to 84 years with
      AD measured with magnetic resonance imaging and with AVC and MVC measured with
      noncontrast cardiac computed tomography scans. Both AVC and MVC were divided into
      3 categories: zero, < median values (low), and >= median values (high) for
      patients with nonzero values. Overall, 88% (n = 3256) and 92% (n = 3365) of
      participants had zero AVC and MVC, while 6% (n = 211) and 4% (n = 156) had low,
      and 6% (n = 209) and 4% (n = 155) had high values of AVC and MVC, respectively.
      The AVC was independently associated with AD after adjusting for age, gender, and
      ethnicity ( P = .035). No association was noted between AVC groups and AD after
      adjustment for all covariates or MVC groups and AD in any model.

PMID- 29025285
TI  - Safety and efficacy of canagliflozin in elderly patients with type 2 diabetes
      mellitus: a 1-year post-marketing surveillance in Japan.
AB  - OBJECTIVE: To evaluate the safety and efficacy of canagliflozin in elderly
      patients with type 2 diabetes mellitus (T2DM) in clinical settings. METHODS: The
      authors conducted a 1-year post-marketing surveillance (PMS) of canagliflozin in
      almost all the elderly patients (>=65 years old) with T2DM who began taking
      canagliflozin during the first 3 months after its launch in Japan. The main
      outcomes included the incidences of adverse drug reactions (ADRs), serious ADRs,
      and the changes of laboratory tests as well as efficacy variables. RESULTS: An
      ADR was reported in 9.09% (125 of 1375 patients) in the safety analysis set. The
      main ADRs were dehydration, constipation, thirst, pollakiuria, dizziness,
      cystitis, eczema, pruritus, and rash. The incidence of serious ADRs was 1.02% (14
      patients), which included urinary tract infection, dehydration, hypoglycemia, and
      cerebral infarction (two patients each). ADRs of special interest that had been
      reported in clinical trials of SGLT2 inhibitors, such as hypoglycemia, volume
      depletion-related events, genital/urinary tract infection, polyuria/pollakiuria,
      and ketone body increased were also observed in this PMS. The safety profiles
      were similar to the results of a previous clinical study of canagliflozin, and
      new safety concerns were not identified in this survey. The mean change in HbA1c
      was -0.77% after 12 months of treatment in the efficacy analysis set. CONCLUSION:
      In this PMS, the safety and efficacy profiles of canagliflozin in elderly
      patients with T2DM were obtained in the clinical settings in Japan and the drug
      was well tolerated and effective in improving glycemic control.

PMID- 29025286
TI  - [Thalidomide therapy in relapsed diffuse large B-cell lymphoma in elderly
      patients. Three cases].
AB  - Diffuse large B-cell lymphoma (DLBCL), a high-grade lymphoproliferative disease,
      is the most common lymphoma in adults, representing 31% of non-Hodgkin lymphomas
      (NHL). In elderly patients treatment is problematic because of the high toxicity
      of standard chemotherapy protocols, especially in relapsed cases, where high-dose
      chemotherapy and haematopoietic stem cell transplantation would be the best
      choice. More and more data is becoming available on alternative treatment of
      refractory/relapsed NHL, including studies on the positive effect of thalidomide
      and second generation IMiDs in DLBCL, which are already part of the standard
      treatment protocol in myeloma multiplex and myelodysplasia. The broadening use of
      IMiDs is due to their anti-angiogenetic, immunmodulatory and anti-inflammatory
      properties. In addition, a component of the E3-ubiquitin ligase complex, named
      cereblon, has been described in 2010 as the molecular effector of the thalidomide
      signal transduction pathway. We initiated thalidomide treatment in three elderly
      patients with relapsed DLBCL. In two cases, patients had CNS involvement, in the
      third case the patient had primary mediastinal disease. Patients received 100 mg
      thalidomide in combination with corticosteroids. Two patients showed an excellent
      response reaching complete remission on imaging; these patients are progression
      free 12 and 20 months after the beginning of treatment. One patient with CNS
      involvement progressed and deceased despite therapy. According to the literature,
      IMiDs have significant activity in relapsed DLBCL. Our case-report presents
      promising results in an elderly patient population with aggressive relapsed NHL
      that usually has very poor outcome, as high-toxicity treatment cannot be given to
      these patients. Consequently, because of its efficiency, low-cost and low
      toxicity, it is recommended to consider thalidomide therapy in elderly patients
      with high-grade DLBCL. Orv Hetil. 2017; 158(41): 1642-1648.

PMID- 29025287
TI  - [Incidence and treatment of extranodal natural killer/T-cell lymphoma nasal type.
      Hungarian experiences].
AB  - INTRODUCTION: Extranodal natural killer/T (NK/T) cell lymphoma, nasal type
      (ENKTL) represents a rare subtype of T-cell lymphomas with aggressive clinical
      behavior according to WHO 2016 classification. AIM: ENKTL has distinctive
      geographic distribution with higher incidence in Asia and Latin America (10% of
      all non-Hodgkin lymphoma cases), than in Europe and North America (<1%). ENKTL
      tipically origins from nasopharynx and upper aerodigestive tract. Anthracycline
      based chemotherapy regimens are largely ineffective in the treatment of ENKTL.
      METHOD: Our aims were to evaluate the incidence and treatment strategies of ENKTL
      patients in Hungarian Haematological Centres between 2003 and 2015. Altogether 20
      patients with ENKTL were treated in the 4 haematological hospitals (male:female
      ratio 12:8, with median 49.5 years of age). RESULTS: Ten patients had localized
      (stage I-II) disease at the time of the diagnosis. Seventeen patients were
      treated with chemotherapy (11/CHOP, CHOP-like, 2/HyperCVAD, 1/ProMACECytaBom,
      1/SMILE, 2/others), which was completed with involved-field radiation therapy
      (IFRT) (40-46 Gy) in 6 cases were used. After first-line therapy 9 patients
      achieved complete remission (CR), 3 patients had partial remission (PR), 3
      patients had progressive disease (PD), and 2 patients had stable disease (SD).
      Median follow-up was 32 (3-113) months. Five patients received second-line
      therapy for progressive or recurrent disease [2/DHAP, 1/VIM, 1/HyperCVAD,
      1/ProMACECytaBom]. None of the patients achieved CR after second-line therapy.
      Two patients have undergone autologous hematopoietic stem cell transplantation
      (HSCT) after the first CR. CONCLUSION: ENKTL treatment is more effective with
      nonanthracycline-containing regimens. L-asparaginase containing chemotherapy and
      concurrent or sequential chemo-radiotherapy improves survival and CR rates. Orv
      Hetil. 2017; 158(41): 1635-1641.

PMID- 29025288
TI  - [State of the art molecular diagnostics and therapy of chronic lymphocytic
      leukaemia in the era of new targeted therapies].
AB  - Chronic lymphoid leukaemia (CLL) has a heterogeneous clinical course depending on
      many clinical and molecular prognostic markers, which play an important role in
      the selection of the best treatment option. So far, TP53 disruption is the key
      prognostic and predictive factor assisting treatment decisions, especially in the
      era of novel therapies. Asymptomatic patients in early stages of the disease will
      still benefit from watchful waiting. In the frontline setting, chemoimmunotherapy
      is still the standard care in the majority of standard risk CLL patients. New
      classes of drugs like kinase inhibitors and BCL-2 inhibitors (ibrutinib,
      idelalisib and venetoclax) are the treatment of choice in CLL patients with
      relapsed/refractory disease, with the exception of high risk disease, where the
      optimal treatment is frontline ibrutinib monotherapy. In the near future,
      integrating next generation sequencing into the routine diagnostics would help
      the development of individual CLL patient management and to choose an optimal
      treatment strategy. Orv Hetil. 2017; 158(41): 1620-1629.

PMID- 29025290
TI  - [Editor's commentary].

PMID- 29025289
TI  - [The role of autologous hemopoietic stem cell transplantation in T-cell lymphoma.
      Hungarian data].
AB  - T-cell lymphoma is a poor prognostic hematological malignancy. The generally used
      - not sufficiently effective - induction chemotherapy should be improved with
      consolidative autologous hemopoetic stem cell transplantation. The authors
      describe the role, place and effectiveness of transplantation in this disorder.
      One hundred thirty three autologous stem cell transplantations were performed in
      the last 22 years in Hungary. Detailed results are available from the last 6
      years. In this period 43 transplantations were carried out in 4 Hungarian
      centers. Carmustine-etoposide-cytosine arabinoside-melphalan (BEAM) conditioning
      regimen was used in 95%. The transplantation was done mainly in complete
      remission (84%), 1 year after transplantation 65% of patients were still in
      complete remission. Eleven patients died, 82% of them have progressive disease.
      Brentuximab vedotin has already proved the effectiveness, several other
      chemoterapeutics, monoclonal antibodies, kinase inhibitors are under
      investigation. In certain cases allogeneic stem cell transplantation has real
      indication among therapeutic options. Orv Hetil. 2017; 158(41): 1615-1619.

PMID- 29025291
TI  - [Waldenstrom's macroglobulinemia and its individualized therapy options].
AB  - Waldenstrom's macroglobulinaemia is a form of lymphoplasmocytic lymphoma that
      preferentially localizes to the bone marrow and causes a special syndrome
      characterized by monoclonal IgM hypersecretion. Recent results point to the fact
      that this disease has at least three different pathobiological forms with
      different clinical presentation. While mutations of MYD88 occur in 95-97% of the
      cases, there are CXCR4 mutations in 30-40%, ARID1A mutations in 17% and CD79B
      mutations in approximately 10% of afflicted individuals. CXCR pathway signaling
      is able to transcriptionally silence tumor suppressors induced by MYD88
      activation. Patients with mutated MYD88 and CXCR4 present with higher tumor
      burden, slower developing and less deep response upon therapy with more frequent
      resistance. In this review, based on the most recent data, a treatment selection
      advice is provided for the therapy of symptomatic patients. Orv Hetil. 2017;
      158(41): 1604-1614.

PMID- 29025292
TI  - [Brentuximab vedotin treatment in patients with relapsed or refractory Hodgkin
      lymphoma. A Hungarian retrospective study].
AB  - INTRODUCTION: The treatment of relapsed or refractory Hodgkin lymphoma is still a
      major therapeutic challenge. The use of brentuximab vedotin, an anti-CD30
      antibody-drug conjugate, represents a promising approach for these patients,
      however clinical outcomes have not yet been evaluated in Hungary. AIM: Our aim
      was to assess the efficacy, safety and outcome of brentuximab vedotin treatment
      in Hungarian Hodgkin lymphoma patients. METHOD: In this retrospective case note
      review we enrolled patients at 6 clinical sites countrywide who were diagnosed
      with Hodgkin lymphoma and received brentuximab vedotin between 1 January 2013 and
      31 December 2016. RESULTS: A total of 86 patients were treated with brentuximab
      vedotin during the examined period. Before therapy initiation 66% of our patients
      had advanced-stage disease. Overall response rate to brentuximab vedotin,
      administered before autologous hematopoietic stem cell transplantation (n = 54)
      was 66.6%, complete remission rate was 42.6%. Thirty patients received
      brentuximab vedotin after AHSCT, 46.67% responded to treatment, 30% achieved
      complete remission. Thirty-six patients received the drug as a single-agent
      therapy, 50 patients were given brentuximab vedotin in combination, 39 of them
      with bendamustin. Toxicity was observed only in 13.95% of our patients, most
      common symptom was skin rash. Based on our analysis the estimated 5-year overall
      survival rate was 78.7%, the estimated progression free survival rate was 23.59
      months (95% CI: 19.50-27.68). CONCLUSION: Brentuximab vedotin carries a
      substantial improvement in the treatment of relapsed or refractory Hodgkin
      lymphoma. Our results underline prior observations published in the literature.
      The use of brentuximab vedotin in combination can be beneficial, however further
      investigation is needed on the subject. Orv Hetil. 2017; 158(41): 1630-1634.

PMID- 29025293
TI  - Berberine Induces Apoptotic Cell Death via Activation of Caspase-3 and -8 in HL
      60 Human Leukemia Cells: Nuclear Localization and Structure-Activity
      Relationships.
AB  - Berberine (BBR), an isoquinoline alkaloid, is a well-known bioactive compound
      contained in medicinal plants used in traditional and folk medicines. In this
      study, we investigated the subcellular localization and the apoptotic mechanisms
      of BBR were elucidated. First, we confirmed the incorporation of BBR into the
      cell visually. BBR showed antiproliferative activity and promptly localized to
      the nucleus from 5[Formula: see text]min to 15[Formula: see text]min after BBR
      treatment in HL-60 human promyelocytic leukemia cells. Next, we examined the
      antiproliferative activity of BBR (1) and its biosynthetically related compounds
      (2-7) in HL-60 cells. BBR exerted strongest antiproliferative activity among 1-7
      and the results of structures and activity relation suggested that a
      methylenedioxyl group in ring A, an [Formula: see text]-alkyl group at C-9
      position, and the frame of isoquinoline may be necessary for antiproliferative
      activity. Moreover, BBR showed the most potent antiproliferative activity in HL
      60 cells among human cancer and normal cell lines tested. Next, we examined the
      effect of BBR on molecular events known as apoptosis induction. In HL-60 cells,
      BBR induced chromatin condensation and DNA fragmentation, and triggered the
      activation of PARP, caspase-3 and caspase-8 without the activation of caspase-9.
      BBR-induced DNA fragmentation was abolished by pretreatment with inhibitors
      against caspase-3 and caspase-8, but not against caspase-9. ERK and p38 were
      promptly phosphorylated after 15 min of BBR treatment, and this was correlated
      with time of localization to the nucleus of BBR. These results demonstrated that
      BBR translocated into nucleus immediately after treatments and induced apoptotic
      cell death by activation of caspase-3 and caspase-8.

PMID- 29025294
TI  - The role of the ipsilesional side in the rehabilitation of post-stroke subjects.
AB  - Most stroke lesions occur in the middle cerebral artery territory, presenting a
      high probability of damage of pathways with predominant ipsilesional disposition,
      mainly related to postural control. Despite the high probability of bilateral
      postural control dysfunction based on neuroanatomical fundaments, both research
      and clinical rehabilitation involving stroke subjects have been focused on
      contralesional side (also named affected side) impairments, while ipsilesional
      side (also named non-affected side) impairments have been attributed to an
      adaptive strategy. This paper aims to present a critical understanding about the
      state-of-the-art that sustains the hypothesis that stroke subjects with middle
      cerebral artery territory lesion at the subcortical level show an atypical
      behaviour in the ipsilateral side associated with the lesion itself and the
      possible implications.

PMID- 29025295
TI  - Ultrasonography-guided percutaneous microwave ablation for large hepatic
      cavernous haemangiomas.
AB  - PURPOSE: To evaluate the efficacy and safety of ultrasound-guided percutaneous
      microwave ablation (MWA) for large hepatic cavernous haemangiomas (HCHs) with
      ablation of the feeding artery and aspiration of blood from haemangioma
      simultaneously. MATERIALS AND METHODS: From January 2011 to December 2016, 40
      patients (29 females, 11male; average age 43.25 +/- 7.65 years) with 42 giant
      hepatic haemangiomas (mean diameter 7.02 +/- 1.55 cm, range 4.1-10.8 cm) were
      treated with image-guided percutaneous MWA with ablation of the feeding artery
      and aspiration of blood from haemangioma simultaneously. After MWA, therapeutic
      efficacy was assessed by contrast-enhanced imaging during follow-up. Median
      follow-up time was 24 months (range 6-60 months). RESULTS: Technical
      effectiveness rate was 100% with a mean ablation time of 1175 +/- 516 (range 480
      2340) seconds. The mean number of antenna insertions was 3.82 +/- 1.23 for each
      lesion. Clinical effectiveness rate was 95% (38/40). There was a significant
      decrease of the tumour volume within three days after ablation compared with
      before ablation (p < 0.001). The mean tumour volume shrinkage rate was 59.67 +/-
      16.73% (range 28.20-89.72%) within three days after ablation. Minor complications
      mainly included fever, transient elevation of transaminase, pleura effusion, and
      haemoglobinuria. One patient developed a major complication with acute kidney
      injury (AKI) shortly after MWA, whose renal function gradually recovered after
      haemodialysis. No other severe complications occurred in perioperative and follow
      up periods. CONCLUSIONS: Ultrasound-guided percutaneous MWA for large HCHs with
      ablation of the feeding artery and aspiration of blood from haemangioma
      simultaneously is safe and effective.

PMID- 29025296
TI  - Comment on: Twelve tips for teaching brief motivational interviewing to medical
      students.

PMID- 29025297
TI  - Liver Transplantation in Patients With Cardiac Disease.
AB  - Liver transplantation (LT) is a unique surgical procedure that has major
      hemodynamic and cardiovascular implications. Recently, there has been significant
      interest focused on cardiovascular issues that affect LT patients in all phases
      of the perioperative period. The preoperative cardiac evaluation is a major step
      in the selection of LT candidates. LT candidates are aging in concordance with
      the general population; cardiovascular disease and their risk factors are highly
      associated with older age. Underlying cardiovascular disease has the potential to
      affect outcomes in LT patients and has a major impact on candidate selection. The
      prolonged hemodynamic and metabolic instability during LT may contribute to
      adverse outcomes, especially in patients with underlying cardiovascular disease.
      Cardiovascular events are not unusual during LT; transplant anesthesiologists
      must be prepared for these events. Advanced cardiovascular monitoring techniques
      and treatment modalities are now routinely used during LT. Postoperative
      cardiovascular complications are common in both the early and late posttransplant
      periods. The impact of cardiac complications on posttransplant mortality is well
      recognized. Emerging knowledge regarding cardiovascular disease in LT patients
      and its impact on posttransplant outcomes will have an important role in guiding
      the future perioperative management of LT patients.

PMID- 29025298
TI  - Twelve tips for using applied improvisation in medical education.
AB  - Future physicians will practice medicine in a more complex environment than ever,
      where skills of interpersonal communication, collaboration and adaptability to
      change are critical. Applied improvisation (or AI) is an instructional strategy
      which adapts the concepts of improvisational theater to teach these types of
      complex skills in other contexts. Unique to AI is its very active teaching
      approach, adapting theater games to help learners meet curricular objectives. In
      medical education, AI is particularly helpful when attempting to build students'
      comfort with and skills in complex, interpersonal behaviors such as effective
      listening, person-centeredness, teamwork and communication. This article draws on
      current evidence and the authors' experiences to present best practices for
      incorporating AI into teaching medicine. These practical tips help faculty new to
      AI get started by establishing goals, choosing appropriate games, understanding
      effective debriefing, considering evaluation strategies and managing resistance
      within the context of medical education.

PMID- 29025299
TI  - Simple Decision-Analytic Functions of the AUC for Ruling Out a Risk Prediction
      Model and an Added Predictor.
AB  - BACKGROUND: When using risk prediction models, an important consideration is
      weighing performance against the cost (monetary and harms) of ascertaining
      predictors. METHODS: The minimum test tradeoff (MTT) for ruling out a model is
      the minimum number of all-predictor ascertainments per correct prediction to
      yield a positive overall expected utility. The MTT for ruling out an added
      predictor is the minimum number of added-predictor ascertainments per correct
      prediction to yield a positive overall expected utility. RESULTS: An
      approximation to the MTT for ruling out a model is 1/[P (H(AUCmodel)], where
      H(AUC) = AUC - {1/2 (1-AUC)}1/2, AUC is the area under the receiver operating
      characteristic (ROC) curve, and P is the probability of the predicted event in
      the target population. An approximation to the MTT for ruling out an added
      predictor is 1 /[P {(H(AUCModel:2) - H(AUCModel:1 )], where Model 2 includes an
      added predictor relative to Model 1. LIMITATION: The latter approximation
      requires the Tangent Condition that the true positive rate at the point on the
      ROC curve with a slope of 1 is larger for Model 2 than Model 1. CONCLUSION: These
      approximations are suitable for back-of-the-envelope calculations. For example,
      in a study predicting the risk of invasive breast cancer, Model 2 adds to the
      predictors in Model 1 a set of 7 single nucleotide polymorphisms (SNPs). Based on
      the AUCs and the Tangent Condition, an MTT of 7200 was computed, which indicates
      that 7200 sets of SNPs are needed for every correct prediction of breast cancer
      to yield a positive overall expected utility. If ascertaining the SNPs costs
      $500, this MTT suggests that SNP ascertainment is not likely worthwhile for this
      risk prediction.

PMID- 29025301
TI  - Identifying and removing overlaps from adjacent components is important in
      investigations of C1 modulation by attention.
AB  - During recent years, perceptual/attentional load paradigms have been frequently
      used to investigate whether the initial visual cortical processing can be
      modified by spatial attention. For example, Rauss and colleagues reported
      significant modulations of the earliest component (i.e. the C1) of the visual
      evoked potential (VEP) as a function of attentional load. It may be questioned,
      however, whether these load effects represent modulations of the C1 or overlaps
      from other components. Here we summarize some methods to identify and remove the
      overlaps, which is important to clarify the question of whether the initial
      visual cortical processing could be modulated by attention.

PMID- 29025300
TI  - Levels and patterns of internal migration in Europe: A cohort perspective.
AB  - Europe displays important variations in the level of internal migration, with a
      clear spatial gradient of high mobility in northern and western Europe but lower
      mobility in the south and east. However, cross-national variation in levels of
      internal migration remains poorly understood, because it is analysed almost
      exclusively using cross-sectional data and period measures. This paper seeks to
      advance understanding of cross-national variation in migration levels in 14
      European countries by drawing on a recently proposed suite of migration cohort
      measures, coupled with internationally comparable retrospective residential
      histories. It shows that differences in migration levels are mainly attributable
      to variation in the extent of repeat movement, which is underpinned by the
      differences in mean ages at first and last move that together delineate the
      average length of migration careers. Cohort analysis provides a robust foundation
      for exploring the demographic mechanisms underpinning variation in migration
      levels across countries and over time.

PMID- 29025302
TI  - Medical student healthcare consulting groups: A novel way to train the next
      generation of physician-executives.
AB  - Meeting the challenges of the evolving healthcare environment requires leadership
      of physicians well-trained in clinical medicine and healthcare management.
      However, many physicians lack training in business and leadership. While some
      residency programs have management tracks, training at the medical school level
      is currently lacking. We developed the Hopkins Health Management Advisory Group,
      an extracurricular program at Johns Hopkins University School of Medicine that
      exposes medical students to healthcare management and fosters development of
      leadership skills. Teams of students work directly with health system executives
      on 3-6 month-long projects using management consulting principles to address
      problems spanning health system domains, including strategy, operations, and
      quality improvement. Since the program's inception, 23 students have completed
      seven projects, with 13 additional students currently working on three more
      projects. Sponsors leading six out of seven completed projects have implemented
      recommendations. Qualitative survey respondents have found the program
      beneficial, with students frequently describing how the program has helped to
      develop professional skills and foster knowledge about healthcare management.
      These early assessments show positive impact for both students and the
      institution, and suggest that such programs can train students in management
      early and concurrently in their medication education by immersing them in team
      based health system projects.

PMID- 29025303
TI  - Serum surfactant protein D as a marker for bronchopulmonary dysplasia.
AB  - BACKGROUND: Lung epithelial cells express surfactant protein D (SP-D), a calcium
      dependent lectin that plays an important role in antibody-independent pulmonary
      host defense. Previous studies have shown that it is found in the peripheral
      circulation in patients with pulmonary disease, likely because of translocation
      into the blood when lung epithelial barriers are disrupted by inflammation or
      acute injury. In adults, serum SP-D levels are biomarkers for the progression and
      severity of chronic lung disease. In neonates, elevated SP-D levels in cord blood
      and on day 1 have been associated with prenatal risk factors and with an
      increased risk of respiratory distress syndrome and infections. It is not known
      whether serum SP-D during the first week of life is a marker for bronchopulmonary
      dysplasia (BPD), a form of chronic lung disease of prematurity that is associated
      with lung parenchymal maldevelopment and injury. OBJECTIVE: The goal of this
      study is to determine whether serum SP-D on days 3 and 7 of life are associated
      with the development of BPD in preterm infants. DESIGN/METHODS: Serum samples
      were obtained on postnatal days 3 and 7 from 106 preterm infants (500-2000 g
      birth weight, 23-32-week gestation). SP-D was quantified by Western blot. BPD was
      determined at 36 weeks PMA using NICHD criteria. RESULTS: The mean birth weight
      was 1145 +/- 347 g and gestational age 29.2 +/- 7.4 weeks. BPD was diagnosed in 7
      and "BPD or death" in 16 infants. Days 3 and 7 values tracked significantly (r =
      0.648), and did not correlate with birth weight or gestational age. Contrary to
      expectations, serum SP-D was not associated with BPD. Significant gender
      differences were noted, with SP-D dropping from day 3 to day 7 in males, while
      increasing in females (p < .05). CONCLUSION: Elevated serum SP-D does not appear
      to be a useful marker for BPD. Decreasing serum SP-D levels in males, as compared
      to females, during the first week of life are likely related to gender
      differences in lung maturation, consistent with the higher incidence of BPD in
      males.

PMID- 29025319
TI  - The effects of Salvia przewalskii total phenolic acid extract on immune complex
      glomerulonephritis.
AB  - CONTEXT: Salvia przewalskii Maxim. (Lamiaceae) is a Chinese herbal medicine that
      has long been used for the treatment of cardiovascular disease. OBJECTIVE: The
      study investigated the therapeutic efficacy of S. przewalskii total phenolic acid
      extract (SPE) on immune complex glomerulonephritis (ICG) in rats. MATERIALS AND
      METHODS: Sixty-two Wistar rats were randomized into six groups. ICG was induced
      in all groups except normal control group. SPE was administered intragastrically
      at 24 h intervals for 40 consecutive days. Urine protein (UP), total serum
      protein (TSP), serum albumin (SA), serum cholesterol (SC) and serum urea nitrogen
      (SUN) were measured one day before, on day 20 and 40 after SPE administration. On
      day 40 after SPE administration, the kidneys were removed and prepared into
      pathologic sections. In addition, kidney wet mass was measured for calculating
      the kidney wet mass coefficient (KWMC). RESULTS: UP excretion was reduced
      significantly on day 20 after SPE administration in all three SPE groups as
      compared with that in medium group, and this effect was observable continuously
      until 40 days after SPE administration. Compared with medium group, TSP and SA
      were increased in all three SPE groups after 40 days treatment, while SC and SUN
      were decreased. KWMC was decreased significantly in 100 mg/kg SPE group after 40
      days treatment compared with that in medium group. Histopathologic analyses
      showed that renal inflammatory infiltration and kidney intumesce were alleviated
      in all three SPE groups. CONCLUSIONS: SPE may be a potential therapeutic drug for
      glomerulonephritis.

PMID- 29025320
TI  - Efficacy of itraconazole oral solution using an alternating-week pulse therapy
      regimen for treatment of cats with experimental Microsporum canis infection.
AB  - Objectives The objective of this study was to evaluate itraconazole 10 mg/ml oral
      solution for the treatment of Microsporum canis infection using an alternating
      week pulse therapy regimen in a controlled laboratory setting. Methods Eighty
      cats with experimentally induced infections were randomly assigned to treatment
      (itraconazole vs control [sterile water]), administered 5 mg/kg PO q24h for 1
      week on alternate weeks for 5 weeks, followed by a 4 week follow-up period.
      Topical therapeutic treatment was not administered. Cats were individually housed
      in stainless steel cages that were cleaned and disinfected daily. Study measures
      included weekly fungal cultures, clinical lesion scores, Wood's lamp examination
      and periodic laboratory monitoring. Mycological cure was defined as two
      consecutive negative cultures. Results Itraconazole-treated cats had
      significantly greater ( P = 0.0003) mycological cure compared with untreated
      controls (24/40 [60%] vs 1/40 [2.5%], respectively) and all of these reached
      clinical cure and had negative final Wood's lamp examinations. Furthermore, 36/40
      (90%) treated cats had at least one negative fungal culture by the end of the
      study vs only 3/40 (7.5%) control cats. For both treatment groups, prevalence of
      clinical cure peaked at the end of the study (week 9), with 39/40 (97.5%)
      itraconazole-treated cats and 6/40 (15%) control cats achieving clinical cure.
      Wood's lamp negative examination rates were significantly greater ( P <0.0001)
      for itraconazole-treated cats compared with controls (39/40 cats [97.5%] vs 6/40
      [15%], respectively) and followed the same pattern of improvement as primary
      clinical lesions. Conclusions and relevance In this controlled study, orally
      administered itraconazole using a 5 mg/kg pulse-dose treatment regimen reduced
      the time to mycological cure and increased both mycological and clinical cure
      rates compared with untreated controls.

PMID- 29025322
TI  - Auditory and cognitive development in a partially deaf child with bilateral
      electro-acoustic stimulation: a case study.
AB  - OBJECTIVE: To study the long-term evolution of speech and intelligence in a child
      with partial deafness and normal hearing in the low frequencies after
      sequentially receiving cochlear implants in both ears. DESIGN: Retrospective
      chart review. STUDY SAMPLE: Male child aged 6 years was followed over a time
      period of four years. RESULTS: The paediatric patient had normal hearing up to 1
      kHz and profound hearing loss at all higher frequencies symmetrical in both ears.
      Deprivation of high-frequency sounds resulted in retarded development of speech,
      language and cognitive skills. The choice for rehabilitation was cochlear
      implantation with the aim of preserving a considerable amount of low-frequency
      hearing. With natural hearing at low frequencies and electrical stimulation at
      high frequencies, the child was able to compensate most of his developmental
      deficits. Moreover, spatial hearing was almost normal. CONCLUSIONS: Electro
      natural stimulation without amplification of the low frequencies (electro-natural
      hearing) provides access to the whole audible frequency range for children, who
      suffer from partial deafness in the high frequencies and are normal hearing at
      low frequencies. Such provision allows for regular speech development and favours
      the development of spatial hearing. The case report also demonstrates a strong
      impact on intellectual performance.

PMID- 29025321
TI  - Rutin ameliorates oxidative stress and preserves hepatic and renal functions
      following exposure to cadmium and ethanol.
AB  - CONTEXT: Rutin (RUT) is an antioxidant flavonoid with well-known metal chelating
      potentials. OBJECTIVE: This study was designed to evaluate the protective effects
      of RUT against cadmium (Cd) + ethanol (EtOH)-induced hepatic and renal toxicity
      in rats. MATERIALS AND METHODS: Wistar rats were treated with Cd (50 mg/kg) alone
      or in combination with EtOH (5 mg/kg) and RUT (25, 50 and 100 mg/kg) for 15 days.
      After treatment, the liver, kidney and serum were removed for biochemical assays
      by spectrophotometric methods. RESULTS: Serum, hepatic and renal malondialdehyde
      (MDA) levels were highest in the Cd + EtOH group and lowest in Cd + EtOH animals
      co-treated with the highest dose of RUT (2.98 +/- 0.34, 10.08 +/- 2.32, 4.99 +/-
      1.21 vs. 1.69 +/- 0.33, 6.13 +/- 0.28, 3.66 +/- 1.12 MUmol MDA/mg protein,
      respectively). The serum level of Cd was increased in the Cd + EtOH treated
      animals compared to Cd + EtOH animals co-treated with 100 mg/kg RUT (2.54 +/-
      0.08 vs. 1.28 +/- 0.04 ppm). Furthermore, RUT at the highest dose protected
      against Cd + EtOH-induced elevation of bilirubin and uric acid levels as well as
      activities of lactate dehydrogenase and gamma-glutamyl transferase (62.86 +/-
      2.74 vs. 122.52 +/- 6.35 umol/L; 1.77 +/- 0.35 vs. 3.23 +/- 0.55 mmol/L; 9.56 +/-
      1.22 vs. 16.21 +/- 1.64 U/L; 288.92 +/- 40.12 vs. 159.8 +/- 18.01 U/L). The histo
      pathological changes in the liver and kidney were also reduced in the Cd + EtOH
      animals co-treated with RUT in a dose-dependent manner. DISCUSSION AND
      CONCLUSION: RUT protected against the combined effects of Cd + EtOH on hepatic
      and renal functions and improved the antioxidant defence system in the blood.

PMID- 29025323
TI  - Cardiovascular Autonomic Responses in the VCD Rat Model of Menopause: Effects of
      Short- and Long-Term Ovarian Failure.
AB  - After menopause, hypertension elevates the risk of cardiac diseases, one of the
      major causes of women's morbidity. The gradual depletion of ovarian follicles in
      rats, induced by 4-vinylcyclohexene diepoxide (VCD), is a model for studying the
      physiology of menopause. 4-Vinylcyclohexene diepoxide treatment leads to early
      ovarian failure (OF) and a hormonal profile comparable to menopause in humans. We
      have hypothesized that OF can compromise the balance between sympathetic and
      parasympathetic tones of the cardiovascular system, shifting toward dominance of
      the former. We aimed to study the autonomic modulation of heart and blood vessels
      and the cardiovascular reflexes in rats presenting short-term (80 days) or long
      term (180 days) OF induced by VCD. Twenty-eight-day-old Wistar rats were
      submitted to VCD treatment (160 mg/kg, intraperitoneally) or vehicle (control)
      for 15 consecutive days and experiments were conducted at 80 or 180 days after
      the onset of treatment. Long-term OF led to an increase in the sympathetic
      activity to blood vessels and an impairment in the baroreflex control of the
      heart, evoked by physiological changes in arterial pressure. Despite that, long
      term OF did not cause hypertension during the 180 days of exposure. Short-term OF
      did not cause any deleterious effect on the cardiovascular parameters analyzed.
      These data indicate that long-term OF does not disrupt the maintenance of
      arterial pressure homeostasis in rats but worsens the autonomic cardiovascular
      control. In turn, this can lead to cardiovascular complications, especially when
      associated with the aging process seen during human menopause.

PMID- 29025324
TI  - The effects of head-cooling on brain function during passive hyperthermia: an
      fMRI study.
AB  - PURPOSE: To investigate the effect of head-cooling on resting-state spontaneous
      brain activity during passive hyperthermia. METHODS: An environmental heat
      exposure was simulated on 16 healthy men under a normal control condition (NC) at
      25  degrees C and two hot conditions at 50  degrees C with hyperthermia with head
      cooling condition (HHC) and without hyperthermia condition (HOT) keeping the head
      cool, respectively. Resting-state functional MRI (fMRI) data were acquired under
      each condition and the values of amplitude low frequency fluctuations (ALFF) and
      z functional connectivity (zFC) were computed to examine regional activity and
      functional integration, respectively. Pearson's correlation analysis between the
      ALFF value and subjective sensations scores were performed. RESULTS: Brain
      regions with significant ALFF differences among the three conditions were found
      primarily in the right medial prefrontal cortex/anterior cingulate cortex
      (MPFC/ACC), bilateral posterior cingulate cortex/precuneus (PCC/PCu), and right
      fusiform gyrus. Compared to the NC or HOT condition, the HHC condition exhibited
      significantly increased ALFF in the bilateral PCC/PCu and decreased ALFF in the
      right fusiform gyrus. However, ALFF of the right MPFC/ACC showed no significant
      difference between the NC and HHC conditions. Positive FC between the right
      MPFC/ACC and bilateral PCC/PCu was significantly increased in HHC condition with
      respect to HOT condition. Negative FC between the right fusiform gyrus and the
      right MPFC/ACC, bilateral PCC/PCu was observed with a decreasing trend from the
      HHC condition to the HOT condition. Moreover, head-cooling also improved thermal
      comfort during passive hyperthermia. CONCLUSIONS: Head-cooling could
      substantially reduce the negative effect of hyperthermia on human brain activity
      as well as thermal sensation.

PMID- 29025326
TI  - Onco-proteogenomics: Multi-omics level data integration for accurate phenotype
      prediction.
AB  - The overall goal of translational oncology is to identify molecular alterations
      indicative of cancer or of responsiveness to specific therapeutic regimens. While
      next-generation sequencing has played a pioneering role in this quest, the latest
      advances in proteomic technologies promise to provide a holistic approach to the
      further elucidation of tumor biology. Genetic information may be written in DNA
      and flow from DNA to RNA to protein, according to the central dogma of molecular
      biology, but the observed phenotype is dictated predominantly by the DNA protein
      coding region-derived proteotype. Proteomics holds the potential to bridge the
      gap between genotype and phenotype, because the powerful analytical tool of mass
      spectrometry has reached a point of maturity to serve this purpose effectively.
      This integration of "omics" data has given birth to the novel field of onco
      proteogenomics, which has much to offer to precision medicine and personalized
      patient management. Here, we review briefly how each "omics" technology has
      individually contributed to cancer research, discuss technological and
      computational advances that have contributed to the realization of onco
      proteogenomics, and summarize current and future translational applications.

PMID- 29025325
TI  - Versatility of targeted antibiotic-loaded gold nanoconstructs for the treatment
      of biofilm-associated bacterial infections.
AB  - BACKGROUND: We previously demonstrated that a photoactivatable therapeutic
      approach employing antibiotic-loaded, antibody-conjugated, polydopamine (PDA)
      coated gold nanocages (AuNCs) could be used for the synergistic killing of
      bacterial cells within a biofilm. The approach was validated with a focus on
      Staphylococcus aureus using an antibody specific for staphylococcal protein A
      (Spa) and an antibiotic (daptomycin) active against Gram-positive cocci including
      methicillin-resistant S. aureus (MRSA). However, an important aspect of this
      approach is its potential therapeutic versatility. METHODS: In this report, we
      evaluated this versatility by examining the efficacy of AuNC formulations
      generated with alternative antibodies and antibiotics targeting S. aureus and
      alternative combinations targeting the Gram-negative pathogen Pseudomonas
      aeruginosa. RESULTS: The results confirmed that daptomycin-loaded AuNCs
      conjugated to antibodies targeting two different S. aureus lipoproteins
      (SACOL0486 and SACOL0688) also effectively kill MRSA in the context of a biofilm.
      However, our results also demonstrate that antibiotic choice is critical.
      Specifically, ceftaroline and vancomycin-loaded AuNCs conjugated to anti-Spa
      antibodies were found to exhibit reduced efficacy relative to daptomycin-loaded
      AuNCs conjugated to the same antibody. In contrast, gentamicin-loaded AuNCs
      conjugated to an antibody targeting a conserved outer membrane protein were
      highly effective against P. aeruginosa biofilms. CONCLUSIONS: These results
      confirm the therapeutic versatility of our approach. However, to the extent that
      its synergistic efficacy is dependent on the ability to achieve both a lethal
      photothermal effect and the thermally controlled release of a sufficient amount
      of antibiotic, they also demonstrate the importance of carefully designing
      appropriate antibody and antibiotic combinations to achieve the desired
      therapeutic synergy.

PMID- 29025327
TI  - Post-herpetic neuralgia - a review of current management and future directions.
AB  - INTRODUCTION: Post-herpetic neuralgia (PHN) is common and treatment is often
      suboptimal with less than half of patients achieving adequate 50% pain relief. As
      an area of unmet clinical need and as an archetype of neuropathic pain, it
      deserves the attention of clinicians and researchers. Areas covered: This review
      summarises the epidemiology, pathophysiology, risk factors and clinical features
      of varicella infection. It describes the current and possible future management
      strategies for preventing varicella infection and reactivation and for treating
      PHN. Expert opinion: A highly successful Varicella Zoster (VZV) vaccine has not
      been universally adopted due to fears that it may increase Herpes Zoster (HZ)
      incidence - and thus PHN - in older, unvaccinated generations. This is a
      controversial theory but advances in the efficacy of vaccines against HZ may
      allay these fears and encourage more widespread adoption of the VZV vaccine.
      Treatment of PHN, as for any neuropathic pain, must be multidisciplinary and
      multimodal. Advances in sensory phenotyping technology and genomics may allow
      more individualised treatment. Traditional research methodologies are ill-suited
      to assess the kind of complex interventions that are necessary to achieve better
      clinical outcomes in this challenging field.

PMID- 29025328
TI  - Safety Assessment of Cross-Linked Alkyl Acrylates as Used in Cosmetics.
AB  - The Cosmetic Ingredient Review (CIR) Expert Panel assessed the safety of cross
      linked alkyl acrylates as used in cosmetics. The 23 cross-linked alkyl acrylates
      included in this safety assessment are reported to function as absorbents, film
      formers, emulsion stabilizers, viscosity increasing agents, suspending agents,
      binders, and/or skin-conditioning agents. The Panel reviewed available animal and
      clinical data, as well as information from previous CIR reports on monomer
      components. Because data were not available for the individual ingredients, and
      because residual monomer may be present, the Panel extrapolated from previous
      reports to support safety. The Panel concluded that cross-linked alkyl acrylates
      are safe in the present practices of use and concentration, provided that they
      are not polymerized in benzene. For those ingredients polymerized in benzene, the
      data available were insufficient to make a determination of safety. A risk
      assessment for the amount of benzene present would be needed.

PMID- 29025329
TI  - m-Phenylenediamine and m-Phenylenediamine Sulfate.

PMID- 29025330
TI  - 40th Anniversary Overview and Rereview Summaries From 2011 to 2015.

PMID- 29025331
TI  - Polyvinyl Alcohol.

PMID- 29025332
TI  - Quaternium-15.

PMID- 29025333
TI  - Iodopropynyl Butylcarbamate.

PMID- 29025334
TI  - Polyvinyl Acetate.

PMID- 29025335
TI  - HC Red No. 1.

PMID- 29025337
TI  - PVP (Polyvinylpyrrolidone).

PMID- 29025336
TI  - Methyldibromo Glutaronitrile.

PMID- 29025338
TI  - HC Orange No. 1.

PMID- 29025339
TI  - Bisabolol.

PMID- 29025340
TI  - HC Yellow No. 4.

PMID- 29025342
TI  - Dibutyl, Dimethyl, and Diethyl Phthalate and Butyl Benzyl Phthalate.

PMID- 29025341
TI  - 2-Amno-6-Chloro-4-Nitrophenol.

PMID- 29025343
TI  - Retinol and Retinyl Palmitate.

PMID- 29025344
TI  - Glutaral.

PMID- 29025345
TI  - The Cosmetic Ingredient Review Program-Expert Safety Assessments of Cosmetic
      Ingredients in an Open Forum.
AB  - The Cosmetic Ingredient Review (CIR) is a nonprofit program to assess the safety
      of ingredients in personal care products in an open, unbiased, and expert manner.
      Cosmetic Ingredient Review was established in 1976 by the Personal Care Products
      Council (PCPC), with the support of the US Food and Drug Administration (USFDA)
      and the Consumer Federation of America (CFA). Cosmetic Ingredient Review remains
      the only scientific program in the world committed to the systematic, independent
      review of cosmetic ingredient safety in a public forum. Cosmetic Ingredient
      Review operates in accordance with procedures modeled after the USFDA process for
      reviewing over-the-counter drugs. Nine voting panel members are distinguished,
      such as medical professionals, scientists, and professors. Three nonvoting
      liaisons are designated by the USFDA, CFA, and PCPC to represent government,
      consumer, and industry, respectively. The annual rate of completing safety
      assessments accelerated from about 100 to more than 400 ingredients by
      implementing grouping and read-across strategies and other approaches. As of
      March 2017, CIR had reviewed 4,740 individual cosmetic ingredients, including
      4,611 determined to be safe as used or safe with qualifications, 12 determined to
      be unsafe, and 117 ingredients for which the information is insufficient to
      determine safety. Examples of especially challenging safety assessments and
      issues are presented here, including botanicals. Cosmetic Ingredient Review
      continues to strengthen its program with the ongoing cooperation of the USFDA,
      CFA, the cosmetics industry, and everyone else interested in contributing to the
      process.

PMID- 29025346
TI  - Alpha Hydroxy Acids.

PMID- 29025347
TI  - 4-Chlororesorcinol.

PMID- 29025348
TI  - Safety Assessment of Diethanolamine and Its Salts as Used in Cosmetics.
AB  - The Cosmetic Ingredient Review (CIR) Expert Panel assessed the safety of
      diethanolamine and its salts as used in cosmetics. Diethanolamine functions as a
      pH adjuster; the 16 salts included in this rereview reportedly function as
      surfactants, emulsifying agents, viscosity increasing agents, hair or skin
      conditioning agents, foam boosters, or antistatic agents. The Panel reviewed
      available animal and clinical data, as well as information from previous CIR
      reports. Since data were not available for each individual ingredient, and since
      the salts dissociate freely in water, the Panel extrapolated from previous
      reports to support safety. The Panel concluded that diethanolamine and its salts
      are safe for use when formulated to be nonirritating. These ingredients should
      not be used in cosmetic products in which N-nitroso compounds can be formed.

PMID- 29025349
TI  - Isostearamidopropyl Morpholine Lactate.

PMID- 29025350
TI  - The patient with a complex chronic respiratory disease: a specialist of his own
      life?
AB  - INTRODUCTION: The independent and central role of the patient with a complex
      chronic respiratory disease in targeted, personalized disease management
      strategies is becoming increasingly important. Patients are the ones living with
      the disease and are finally responsible for their lives underlining their role as
      essential members of the interdisciplinary treatment team. Areas covered: The
      present paper narratively reviews existing research and discusses the special, as
      well as specialized, role of the patient with a complex chronic respiratory
      disease in the healthcare system and highlights fundamental elements of the
      (future) relationship between patient and healthcare professionals. Expert
      commentary: Since the chronic respiratory disease at hand is part of the
      patient's entire life, we need holistic, personalized approaches optimizing
      patients' quality of life by not only treating the disease but considering the
      patients' whole environment and where healthcare professionals and patients are
      co-creating value care.

PMID- 29025351
TI  - Utilization of robotic-arm assisted total knee arthroplasty for soft tissue
      protection.
AB  - Despite the well-established success of total knee arthroplasty (TKA), iatrogenic
      ligamentous and soft tissue injuries are infrequent, but potential complications
      that can have devastating impact on clinical outcomes. These injuries are often
      related to technical errors and excessive soft tissue manipulation, particularly
      during bony resections. Recently, robotic-arm assisted TKA was introduced and
      demonstrated promising results with potential technical advantages over manual
      surgery in implant positioning and mechanical accuracy. Furthermore, soft tissue
      protection is an additional potential advantage offered by these systems that can
      reduce inadvertent human technical errors encountered during standard manual
      resections. Therefore, due to the relative paucity of literature, we attempted to
      answer the following questions: 1) does robotic-arm assisted TKA offer a
      technical advantage that allows enhanced soft tissue protection? 2) What is the
      available evidence about soft tissue protection? Recently introduced models of
      robotic-arm assisted TKA systems with advanced technology showed promising
      clinical outcomes and soft tissue protection in the short- and mid-term follow-up
      with results comparable or superior to manual TKA. In this review, we attempted
      to explore this dimension of robotics in TKA and investigate the soft tissue
      related complications currently reported in the literature.

PMID- 29025353
TI  - Mass spectrometry based proteomics analyses in kallikrein-related peptidase
      research: implications for cancer research and therapy.
AB  - INTRODUCTION: Kallikrein-related peptidases (KLKs) are a family of serine
      peptidases that are deregulated in numerous pathological conditions, with a
      multitude of KLK-mediated functional roles implicated in the progression of
      cancer. Advances in multidimensional mass spectrometry (MS)-based proteomics have
      facilitated the quantitative measurement of deregulated KLK expression in cancer,
      identifying certain KLKs, as well as their substrates, as potential cancer
      biomarkers. Areas covered: In this review, we discuss how these approaches have
      been utilized for KLK biomarker discovery and unbiased substrate determination in
      complex protein pools that mimic the in vivo extracellular microenvironment.
      Expert commentary: Although a limited number of studies have been performed, the
      quantity of information generated has greatly improved our understanding of the
      functional roles of KLKs in cancer progression. In addition, these data suggest
      additional means through which deregulated KLK expression may be targeted in
      cancer treatment, highlighting the potential therapeutic value of these state-of
      the-art MS-based studies.

PMID- 29025352
TI  - Risk of colorectal polyps and of malignancies in asymptomatic carriers of
      mutations in the main DNA mismatch repair genes.
AB  - OBJECTIVE: Mutation carriers (Mut+) in DNA mismatch repair genes are predisposed
      to cancer of various organs and to adenomatous polyps; however, they may remain
      asymptomatic and cancer or polyp-free for several years. We purposed to analyse
      the clinical follow-up of individuals carrying constitutional mutations in the
      MLH1, MSH2 or MSH6 genes who were unaffected by benign polyps or malignant
      tumours at diagnosis. MATERIAL AND METHODS: Mut + subjects (n.81) were members of
      Lynch syndromes in whom mutations were detected between 1993 and 2015; all were
      asymptomatic at diagnosis. They were informed of the cancer risk and surveillance
      was suggested. As controls, 113 nongene carriers (Mut-) in the same Lynch
      families were identified. RESULTS: About one-fourth of the mutation carriers
      developed polyps, mostly adenomas; polyps were less (12%, p < .05) in Mut -
      subjects, and hyperplastic lesions were the prevalent histology. More polyps were
      detected in MLH1 vs. MSH2 mutation carriers. In Mut+, 21 malignant tumours
      developed in 14 carriers vs. 4 tumours in 3 patients among Mut- (p < .001).
      Tumours were mostly of the Lynch spectrum; however, three glioblastomas were
      developed, together with neoplasms of various organs (duodenum, thyroid, skin,
      lung and cervix). Mean age of tumour occurrence was 43.0 years in Mut + vs. 53.0
      among Mut-. CONCLUSIONS: Cancer developed more often in Mut+, with no consistent
      difference between MLH1 and MSH2 carriers. More polyps (mostly adenomas) were
      detected in MLH1 carriers. The majority (13 of 21) of malignant tumours occurred
      in organs for which there is no recommended surveillance, and were lethal in
      three patients.

PMID- 29025354
TI  - Cell-bound complement activation products as lupus biomarkers: diagnosis,
      monitoring and stratification.
AB  - INTRODUCTION: Cell-bound complement activation products (CB-CAPs) were first
      reported in 2004, since which time multiple laboratories have demonstrated their
      value as biomarkers for diagnosis, monitoring, and stratification of patients
      with systemic lupus erythematosus. Areas covered: This review summarizes the
      highlights of these 14 years of CB-CAPs discovery and validation, concluding with
      a view toward their future potential for precision medicine. Expert commentary:
      The practice of medicine is both art and science and each physician can be
      considered both artist and scientist with a variable blend of the two skill sets.
      There is arguably no disease that presents a greater challenge, nor a greater
      opportunity, for implementation of precision medicine, as does lupus. The
      physician who is presented with diagnosis and/or management of a patient
      suspected of having lupus will need to augment artistic skills with scientific
      guidance, and that science will be delivered in the form of biomarkers.
      Ultimately, we will likely have a 'lupus liquid biopsy' that will be 100%
      sensitive and 100% specific for a diagnosis of lupus. This will undoubtedly be a
      panel of biomarkers rather than an individual laboratory test. Such a liquid
      biopsy could transform lupus diagnosis to an entirely scientific process.

PMID- 29025355
TI  - A Content Analysis of Testosterone Websites: Sex, Muscle, and Male Age-Related
      Thematic Differences.
AB  - Male testosterone supplementation is a large and growing industry. How is
      testosterone marketed to male consumers online? The present exploratory study
      entailed a content coding analysis of the home pages of 49 websites focused on
      testosterone supplementation for men in the United States. Four hypotheses
      concerning anticipated age-related differences in content coding were also
      tested: more frequent longevity content toward older men, and more frequent
      social dominance/physical formidability, muscle, and sex content toward younger
      men. Codes were created based on inductive observations and drawing upon the
      medical, life history, and human behavioral endocrinology literatures.
      Approximately half ( n = 24) of websites were oriented toward younger men
      (estimated audience of men 40 years of age or younger) and half ( n = 25) toward
      older men (estimated audience over 40 years of age). Results indicated that the
      most frequent content codes concerned online sales (e.g., product and purchasing
      information). Apart from sales information, the most frequent codes concerned, in
      order, muscle, sex/sexual functioning, low T, energy, fat, strength, aging, and
      well-being, with all four hypotheses also supported. These findings are
      interpreted in the light of medical, evolutionary life history, and human
      behavioral endocrinology approaches.

PMID- 29025357
TI  - Fatherhood in Australian Aboriginal and Torres Strait Islander communities: An
      Examination of Barriers and Opportunities to Strengthen the Male Parenting Role.
AB  - Traditional Australian Aboriginal and Torres Strait Islander societies value
      men's role as parents; however, the importance of promoting fatherhood as a key
      social determinant of men's well-being has not been fully appreciated in Western
      medicine. To strengthen the Aboriginal and Torres Strait Islander male parenting
      role, it is vital to examine current barriers and opportunities. The first author
      (a male Aboriginal health project officer) conducted yarning sessions in three
      remote Australian communities, two being Aboriginal, the other having a high
      Aboriginal population. An expert sample of 25 Aboriginal and 6 non-Aboriginal
      stakeholders, including maternal and child health workers and men's group
      facilitators, considered barriers and opportunities to improve men's parenting
      knowledge and role, with an aim to inform services and practices intended to
      support men's parenting. A specific aim was to shape an existing men's group
      program known as Strong Fathers, Strong Families. A thematic analysis of data
      from the project identified barriers and opportunities to support men's role as
      parents. Challenges included the transition from traditional to contemporary
      parenting practices and low level of cultural and male gender sensitivity in
      maternal and child health services. Services need to better understand and focus
      on men's psychological empowerment and to address shame and lack of confidence
      around parenting. Poor literacy and numeracy are viewed as contributing to
      disempowerment. Communities need to champion Aboriginal and Torres Strait
      Islander male father role models. Biases and barriers should be addressed to
      improve service delivery and better enable men to become empowered and confident
      fathers.

PMID- 29025358
TI  - Men's Perceptions of Women's Participation in Development Initiatives in Rural
      Bangladesh.
AB  - Without taking masculine issues into account, women's participation in
      development initiatives does not always guarantee their empowerment, health, and
      welfare in a male-dominated society. This study aimed to explore men's
      perceptions of women's participation in development (WPD) in rural Bangladesh. In
      adopting a qualitative approach, the study examined 48 purposively selected
      married and unmarried men aged 20-76 years in three northwest villages. Data
      collection was accomplished through four focus group discussions (FGDs) with 43
      men clustered into four groups and through individual interviews with five other
      men. A qualitative content analysis of the data revealed an overall theme of
      "feeling challenged by fears and hopes," indicating variations in men's views on
      women's participation in development initiatives as represented by three main
      categories: (a) fearing the loss of male authority, (b) recognizing women's roles
      in enhancing family welfare, and (c) valuing women's independence. In the context
      of dominant patriarchal traditions in Bangladesh, these findings provide new
      insight into dynamics and variations of men's views, suggesting a need to better
      engage men during different stages of women-focused development initiatives.

PMID- 29025356
TI  - Associations Between Sleep Deprivation and Salivary Testosterone Levels in Male
      University Students: A Prospective Cohort Study.
AB  - Sleep deprivation is a common health problem that is growing rapidly worldwide
      and it is associated with short- and long-term impacts on health. The aim of this
      study was to detect potential predictors of salivary testosterone (sT)
      association with sleep deprivation in Arab male university students. In this
      prospective cohort study, 77 university male students in the age range of 18 to
      26 years were divided into two groups, sleep-deprived (SD) participants and non
      sleep-deprived (NSD) participants. Sleep deprivation was defined as sleeping less
      than 5 hr per night. Blood samples and sT were collected from fasting
      participants to measure serum levels of glucose, lipid profile, leptin,
      serotonin, sT, and body mass index (BMI) values. The multiple linear correlation
      model of high-density lipoprotein cholesterol (HDL-C), BMI, and serotonin was
      positively correlated with sT ( r = .977, p < .05) in the SD group. No
      correlations were identified with sT in the NSD group. In the SD study group, the
      multiple linear regression model of HDL-C, BMI, and serotonin was significantly
      influenced by sT ( R2 = .955, p < .05). These predictors together explained
      approximately 96% of the variance in sT levels in the SD study group. No
      predictive variables for sT were reported in the NSD group. Results indirectly
      confirmed the presence of a positive association between sT and sleep deprivation
      in young men. This association is mediated by three factors, HDL-C, BMI, and
      serum serotonin, which are collectively considered as part of a significant
      physiological adaptation to sleep deprivation in young men.

PMID- 29025359
TI  - BRCA1 or CDK12 loss sensitizes cells to CHK1 inhibitors.
AB  - A broad spectrum of tumors develop resistance to classic chemotherapy,
      necessitating the discovery of new therapies. One successful strategy exploits
      the synthetic lethality between poly(ADP-ribose) polymerase 1/2 proteins and DNA
      damage response genes, including BRCA1, a factor involved in homologous
      recombination-mediated DNA repair, and CDK12, a transcriptional kinase known to
      regulate the expression of DDR genes. CHK1 inhibitors have been shown to enhance
      the anti-cancer effect of DNA-damaging compounds. Since loss of BRCA1 increases
      replication stress and leads to DNA damage, we tested a hypothesis that CDK12- or
      BRCA1-depleted cells rely extensively on S-phase-related CHK1 functions for
      survival. The silencing of BRCA1 or CDK12 sensitized tumor cells to CHK1
      inhibitors in vitro and in vivo. BRCA1 downregulation combined with CHK1
      inhibition induced excessive amounts of DNA damage, resulting in an inability to
      complete the S-phase. Therefore, we suggest CHK1 inhibition as a strategy for
      targeting BRCA1- or CDK12-deficient tumors.

PMID- 29025360
TI  - Best practice of identification and proteomic analysis of extracellular vesicles
      in human health and disease.
AB  - INTRODUCTION: Extracellular vesicles are emerging sources of biomarkers for
      modern preventive and precision medicine. Extracellular vesicles in body fluids
      offer a unique opportunity for integrative biomarker approaches due to their
      complex biocargo that includes proteins, lipids, nucleic acids and metabolites.
      Mass spectrometry-based proteomics data suggest that a significant portion of
      human proteins are sorted into extracellular vesicles and amenable for biomarker
      discovery schemes. Areas covered: this review focuses on key aspects of
      isolation, quality control and subsequent analysis of blood plasma- and
      conditioned medium-derived extracellular vesicle proteins, and summarizes the
      current state-of-the-art in the field. Furthermore, it provides introduction and
      guidelines for mass spectrometry-based proteomic analysis of extracellular
      vesicles. Expert commentary: Comparison of newly developed isolation and
      purification techniques with classical ultracentrifugation-based approaches are
      highly recommended. It is also essential to use multiple analytical approaches to
      characterize the isolated extracellular vesicles prior to characterization of
      their biocargo. Rigor in data reproducibility, critical data analysis, awareness
      of potential pitfalls, standardization and benchmarking are required for
      extracellular vesicle research to fulfil the current expectation that these
      subcellular structures can become a valid source of next generation biomarkers.

PMID- 29025361
TI  - Membrane-bound pyrophosphatase of human gut microbe Clostridium methylpentosum
      confers improved salt tolerance in Escherichia coli, Saccharomyces cerevisiae and
      tobacco.
AB  - Membrane-bound pyrophosphatases (PPases) are involved in the adaption of
      organisms to stress conditions, which was substantiated by numerous plant
      transgenic studies with H+-PPase yet devoid of any correlated evidences for other
      two subfamilies, Na+-PPase and Na+,H+-PPase. Herein, we demonstrate the gene
      cloning and functional evaluation of the membrane-bound PPase (CmPP) of the human
      gut microbe Clostridium methylpentosum. The CmPP gene encodes a single
      polypeptide of 699 amino acids that was predicted as a multi-spanning membrane
      and K+-dependent Na+,H+-PPase. Heterologous expression of CmPP could
      significantly enhance the salt tolerance of both Escherichia coli and
      Saccharomyces cerevisiae, and this effect in yeast could be fortified by N
      terminal addition of a vacuole-targeting signal peptide from the H+-PPase of
      Trypanosoma cruzi. Furthermore, introduction of CmPP could remarkably improve the
      salt tolerance of tobacco, implying its potential use in constructing salt
      resistant transgenic crops. Consequently, the possible mechanisms of CmPP to
      underlie salt tolerance are discussed.

PMID- 29025362
TI  - The partition and transport behavior of cytotoxic ionic liquids (ILs) through the
      DPPC bilayer: Insights from molecular dynamics simulation.
AB  - A molecular dynamics (MD) simulation with atomistic details was performed to
      examine the partitioning and transport behavior of moderately cytotoxic ionic
      liquids (ILs), namely choline bis(2-ethylhexyl) phosphate (CBEH), choline
      bis(2,4,4-trimethylpentyl) phosphinate (CTMP) and choline O,O-diethyl
      dithiophosphate (CDEP) in a fully hydrated dipalmitoylphosphatidylcholine (DPPC)
      bilayer in the fluid phase at 323 K. The structure of ILs was so selected to
      understand if the role of dipole and dispersion forces in the ILs distribution in
      the membrane can be possible. Several analyses including mass density,
      electrostatic potential, order parameter, diffusion coefficients and hydrogen
      bond formation, was carried out to determine the precise location of the anionic
      species inside the membrane. Moreover, the potential of the mean force (PMF)
      method was used to calculate free energy profile for transferring anionic species
      from the DPPC membrane into the bulk water. While less cytotoxic DEP is located
      within the bulk water, more cytotoxic TMP and BEH ILs were found to remain in the
      membrane and the energy barrier for crossing through the bilayer center of BEH
      was higher. Various ILs have no significant effect on P-N vector. The thickness
      of lipid bilayer decreased in all systems comprising ILs, while area per lipid
      increased.

PMID- 29025363
TI  - Identification of core objectives for teaching sustainable healthcare education.
AB  - BACKGROUND: Physicians will be called upon to care for patients who bear the
      burden of disease from the impact of climate change and ecologically
      irresponsible practices which harm ecosystems and contribute to climate change.
      However, physicians must recognize the connection between the climate,
      ecosystems, sustainability, and health and their responsibility and capacity in
      changing the status quo. Sustainable healthcare education (SHE), defined as
      education about the impact of climate change and ecosystem alterations on health
      and the impact of the healthcare industry on the aforementioned, is vital to
      prevention of adverse health outcomes due to the changing climate and
      environment. OBJECTIVE: To systematically determine which and when a set of SHE
      objectives should be included in the medical education continuum. DESIGN: Fifty
      two SHE experts participated in a two-part modified-Delphi study. A survey was
      developed based on 21 SHE objectives. Respondents rated the importance of each
      objective and when each objective should be taught. Descriptive statistics and an
      item-level content validity index (CVI) were used to analyze data. RESULTS:
      Fifteen of the objectives achieved a content validity index of 78% or greater.
      The remaining objectives had content validity indices between 58% and 77%. The
      preclinical years of medical school were rated as the optimal time for
      introducing 13 and the clinical years for introducing six of the objectives.
      Respondents noted the definition of environmental sustainability should be
      learned prior to medical school and identifying ways to improve the environmental
      sustainability of health systems in post-graduate training. CONCLUSIONS: This
      study proposes SHE objectives for the continuum of medical education. These
      objectives ensure the identity of the physician includes the requisite awareness
      and competence to care for patients who experience the impact of climate and
      environment on health and advocate for sustainability of the health systems in
      which they work. ABBREVIATIONS: CVI: Content validity index; SHE: Sustainable
      healthcare education.

PMID- 29025364
TI  - Pharmacokinetic/pharmacodynamic parameters for treatment optimization of
      infection due to antibiotic resistant bacteria: a summary for practical purposes
      in children and adults.
AB  - In the last years, there has been a tremendous increase in the incidence of
      bacterial infections due to resistant strains, especially multi-drug resistant
      Gram-negative bacilli. In Europe, a north to south and a west to east gradient
      was noticed, with more than one third of the K. pneumonia isolates being
      resistant to carbapenems in few countries. New antibiotics are lacking and, as a
      consequence, pharmacokinetic/pharmacodynamic parameters, normalized to pathogen
      minimal inhibitory concentration, are used with increased frequency to treat
      infections due to difficult-to-treat pathogens. These parameters are available at
      least for the adult population, but sparse in many different publications. This
      review wants to provide a comprehensive and 'easy to read' text for everyday
      practice, briefly summarizing the presently available knowledge on
      pharmacokinetic/pharmacodynamic parameters (normalized for minimal inhibitory
      concentration values) of different class drugs, that can be applied for an
      effective antibacterial treatment infections due to antibiotic-resistant
      pathogens.

PMID- 29025366
TI  - Erratum.

PMID- 29025365
TI  - Patient reported outcomes of hand function three years after stroke.
AB  - OBJECTIVE: To comprehensively describe hand function and associated factors among
      stroke survivors by means of the Michigan Hand Outcomes Questionnaire (MHQ; 6
      domains; score 0-100, worst-best). METHODS: In this cross-sectional study, stroke
      patients were invited to complete a set of questionnaires on hand function, socio
      demographic characteristics, mental functioning, daily activities, quality of
      life, and caregiver strain. Stroke characteristics were collected retrospectively
      from medical records. Multiple linear regression analysis adjusted for age, sex,
      and duration of follow-up was used to identify factors associated with MHQ score.
      RESULTS: 207 out of 576 eligible patients responded (36%); mean age 63.8 years
      (SD14.2), 125 males (60.4%). Mean time since stroke was 36.3 months (SD9.9). In
      85% of the patients, the MHQ Total score was less than 100 points (median 79.9,
      IQR 63.0-95.8). The median scores of the domains were: overall hand function
      75.0, daily activities 90.5, work 85.0, pain 100, appearance 93.8, and
      satisfaction with hand function 83.3. A lower MHQ Total score was significantly
      associated with a lower Barthel Index at hospital discharge, a lower level of
      education, a supratentorial stroke and with unfavorable outcomes regarding
      physical and mental functioning, quality of life, and caregiver strain.
      CONCLUSION: Patients can perceive limitations on several domains with respect to
      hand function 2-5 years after stroke. Problems related to the appearance of the
      hand and satisfaction with hand function can be relevant and should be considered
      accordingly. Persistent hand problems after stroke are related to a more severe,
      supratentorial stroke in lower educated patients.

PMID- 29025367
TI  - Narrow QRS tachycardia with AV response from 2:1 to 1:1. What is the mechanism?

PMID- 29025368
TI  - Thinking inside the frame: A framing analysis of the humanities in Danish print
      news media.
AB  - The humanities, the natural and social sciences all represent advanced and
      systematic knowledge production-and they all receive public funding for doing so.
      However, although the field of public understanding of science has been well
      established for decades, similar research attention has not been directed at the
      humanities. The purpose of this study is to argue the case for further research
      of public understanding of the humanities and to take a first step in that
      direction by presenting a study of the framing of the humanities in Danish print
      news media. Different framings of the humanities are analyzed. Despite the
      differences in the issue-specific frames, the generic framing of the humanities
      shared by most articles is as follows: 75% explicitly frame the humanities as
      deficit, while the remaining 25% are more neutral. Consequently, if newspapers
      constitute the only source of information concerning the humanities, newsreaders
      may not be much wiser in understanding what the humanities might be-but they will
      know that whatever the humanities is, it is broken and useless.

PMID- 29025369
TI  - Credibility, expertise and the challenges of science communication 2.0.

PMID- 29025370
TI  - Historical moments in public understanding of science: 1977, The Visible
      Scientists identifies a new scientist for the mass media age.

PMID- 29025371
TI  - Decentralized wastewater treatment using passively aerated biological filter.
AB  - This study aimed to evaluate the efficiency of a novel pilot-scale passively
      aerated biological filter (PABF) as a low energy consumption system for the
      treatment of municipal wastewater. It consists of four similar compartments, each
      containing 40% of a non-woven polyester fabric as a bio-bed. The PABF was fed
      with primary treated wastewater under a hydraulic retention time (HRT) of 3.5 hr
      and a hydraulic loading rate of 5.5 m2/m3/d. The effect of media depth, HRT,
      dissolved oxygen (DO) and surface area of the media on the removal efficiency of
      pollutants was investigated. Results indicated that increasing media depth along
      the axis of the reactor and consequently increasing the HRT and DO resulted in
      great removal of different pollutants. A significant increase in the DO levels in
      the final effluent up to 6.7 mg/l resulted in good nitrification processes.
      Statistical analysis using SPSS showed that the reactor performance has
      significant removal efficiency (p < .05) for all pollutants. Overall results
      indicated that PABF is a viable ecological engineering approach that can be
      optimized and applied to improve water quality with minimal consumption of energy
      and low sludge production compared with conventional activated sludge and
      trickling filter systems.

PMID- 29025372
TI  - Drugs in cardiac arrest: the rise and fall of antiarrhythmics.
AB  - Since the publication of 2000 guidelines for resuscitation, amiodarone is
      considered the antiarrhythmic drug of choice for refractory ventricular
      fibrillation/pulseless ventricular tachycardia. However, to date there is no
      proven benefit in terms of neurologically intact survival to hospital discharge.
      A comprehensive search of the recent literature on amiodarone, nifekalant and
      lidocaine in cardiac arrest was performed. Amiodarone and nifekalant are superior
      to lidocaine with regards to the return of spontaneous circulation and survival
      to hospital admission. Nifekalant shows a trend towards quicker termination of
      ventricular fibrillation compared to amiodarone. There is great uncertainty about
      the efficacy of antiarrhythmics in cardiac arrest. Failure to show improvements
      regarding meaningful survival questions their current use and suggests the need
      for re-evaluating their place in cardiopulmonary resuscitation.

PMID- 29025373
TI  - The prognostic value of high sensitive cardiac troponin I in patients receiving
      cardiac resynchronisation therapy.
AB  - BACKGROUND: Cardiac troponin I (cTnI) is a valuable prognostic biomarker in
      patients with chronic heart failure (CHF). However, the prognostic importance of
      cTnI in patients who received cardiac resynchronisation therapy (CRT) remains
      unknown. The aim of this prospective study was to determine the prognostic value
      of high-sensitive cTnI (hs-cTnI) in CHF patients receiving CRT. METHODS: We
      performed measurements of baseline hs-cTnI levels in CRT patients with ischaemic
      as well as nonischaemic aetiology of CHF, and we investigated their possible
      association with response to CRT and survival of patients. RESULTS: Ninety
      consecutive CRT patients (mean age 64 +/- 9 years, 71 men) were included.
      According to the best cut-off value of hs-cTnI level to predict CRT response and
      all cause mortality, patients were divided into group 1 (hs-cTnI level >=6.5
      ng/l, n = 46) and group 2 (hs-cTnI level <6.5 ng/l, n = 44). During the follow-up
      period (1155 +/- 406 days), 47% of patients were CRT responders (30% in group 1
      and 64% in group 2, p = .002) and 31% of patients died from any cause (48% in
      group 1 and 14% in group 2, p = .001). Regression analysis showed that hs-cTnI
      level <6.5 ng/l was an independent predictor of CRT response (OR 3.49, p = .019)
      and that hs-cTnI level >=6.5 ng/l was an independent predictor of all cause
      mortality (HR 3.01, p = .021). CONCLUSION: The hs-cTnI can be an useful biomarker
      with prognostic value in patients receiving CRT.

PMID- 29025375
TI  - Dopamine-induced SULT1A3/4 promotes EMT and cancer stemness in hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma has the second highest incidence rate among malignant
      cancers in China. Hepatocellular carcinoma development is complex because of the
      metabolism disequilibrium involving SULT1A3/4, a predominant sulfotransferase
      that metabolizes sulfonic xenobiotics and endogenous catecholamines. However, the
      correlation between SULT1A3/4 and hepatocellular carcinoma progression is
      unclear. By utilizing immunofluorescence and immunohistochemical analysis, we
      found that in nine hepatocellular carcinoma clinical specimens, SULT1A3/4 was
      abundantly expressed in tumor tissues compared to that in the adjacent tissues.
      Moreover, liver cancer cells (HepG2, MHCC97-L, and MHCC97-H) had higher basal
      expression of SULT1A3/4 than immortalized liver cells (L02 and Chang liver).
      Ultra-high-pressure liquid chromatography-tandem mass spectrometry assay results
      further revealed that the concentration of dopamine (a substrate of SULT1A3/4)
      was negatively correlated with SULT1A3/4 protein expression. As a transcriptional
      regulator of SULT1A3/4 in turn, dopamine was used to induce SULT1A3/4 in vitro.
      Interestingly, dopamine significantly induced SULT1A3/4 expression in liver
      cancer HepG2 cells, while decreased that in L02 cells. More importantly, the
      expression levels of epithelial-mesenchymal transition biomarkers (N-cadherin and
      vimentin) and cell stemness biomarkers (nanog, sox2, and oct3/4) considerably
      increased in HepG2 with dopamine-induced SULT1A3/4, whereas in L02, epithelial
      mesenchymal transition and cancer stem cell-associated proteins were contrarily
      decreased. Furthermore, invasion and migration assays further revealed that
      dopamine-induced SULT1A3/4 dramatically stimulated the metastatic capacity of
      HepG2 cells. Our results implied that SULT1A3/4 exhibited bidirectional effect on
      tumor and normal hepatocytes and may thus provide a novel strategy for
      hepatocellular carcinoma clinical targeting. In addition, SULT1A3/4 re-expression
      could serve as a biomarker for hepatocellular carcinoma prognosis.

PMID- 29025374
TI  - The prognostic significance of cancer-associated fibroblasts in pancreatic ductal
      adenocarcinoma.
AB  - Cancer-associated fibroblasts are abundant in the desmoplastic stroma of
      pancreatic ductal adenocarcinomas and are considered to play important roles in
      tumor progression. In this study, we investigated the expression status of
      secreted protein acidic and rich in cysteine, periostin, fibroblast-activated
      protein, and the newly developed proCOL11A1 antibody in the stroma of surgically
      resected pancreatic ductal adenocarcinomas and their prognostic implications.
      Tissue microarrays were constructed from 155 surgically resected pancreatic
      ductal adenocarcinomas and paired non-neoplastic pancreata and from another
      independent set of 48 normal/benign pancreata, and immunohistochemical stains
      were performed for proCOL11A1, fibroblast-activated protein, secreted protein
      acidic and rich in cysteine, and periostin. The immunohistochemical stain results
      were correlated with clinicopathological features and survival data. proCOL11A1,
      fibroblast-activated protein, secreted protein acidic and rich in cysteine, and
      periostin expression was significantly increased in the intratumoral stroma of
      pancreatic ductal adenocarcinomas compared to paired non-neoplastic pancreata
      (proCOL11A1: 145/155 (93.5%) vs 26/154 (16.9%); fibroblast-activated protein:
      139/143 (97.2%) vs 82/132 (62.1%); secreted protein acidic and rich in cysteine:
      113/150 (75.3%) vs 49/132 (37.1%); periostin: 135/151 (89.4%) vs 45/135 (33.3%);
      p < 0.001, all). While the four markers were expressed at lower levels in
      normal/benign pancreata, there were no significant differences in the expression
      frequencies among normal pancreas, acute pancreatitis, and chronic pancreatitis.
      Interestingly, on survival analysis, low intratumoral fibroblast-activated
      protein+ cancer-associated fibroblast counts (<100/high-power field) were
      associated with a significantly reduced overall survival compared to those with
      high fibroblast-activated protein+ cancer-associated fibroblast counts (p =
      0.010; hazard ratio 5.2 (95% confidence interval 1.3-21.3)). Similar patterns
      were seen for proCOL11A and secreted protein acidic and rich in cysteine and
      overall and disease-free survival, although not statistically significant. In
      conclusion, we demonstrate that the presence of cancer-associated fibroblasts in
      the tumor stroma may not always be associated with a poor prognosis as suggested
      in many studies; on the contrary, it may even be associated with prolonged
      survival, supporting the recent experimental findings that tumor stroma may have
      a protective role rather than enhance aggressive behavior.

PMID- 29025376
TI  - Roles of microRNA let-7b in papillary thyroid carcinoma by regulating HMGA2.
AB  - The incidence of thyroid cancer has increased significantly in the last decade,
      and the most frequent type of this cancer is papillary thyroid carcinoma.
      MicroRNAs have been demonstrated to be abnormally expressed in tumors and
      associated with the development of the tumors. Our aim was to analyze the role
      and molecular mechanisms of tumor suppressor let-7b in the papillary thyroid
      carcinoma. Expression of let-7b and high-mobility group A2 in papillary thyroid
      carcinoma tissues and cell lines was assessed using quantitative reverse
      transcription polymerase chain reaction and western blot analysis. To explore the
      role of let-7b or high-mobility group A2 in the BCPAP and TPC-1 cells, 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell methods were
      used. Let-7b expression was significantly downregulated while expression of high
      mobility group A2 was upregulated dramatically in papillary thyroid carcinoma
      tissues and cells compared with that in normal thyroid tissues and cells. In
      addition, overexpression of let-7b or knockdown of high-mobility group A2
      inhibited cell migration and invasion compared with that of control. Besides,
      high-mobility group A2 was negatively regulated by let-7b in BCPAP cells.
      Moreover, high-mobility group A2 reintroduction reversed the anti-proliferation,
      anti-migration, and anti-invasion roles of let-7b. Let-7b might function as a
      tumor suppressor in papillary thyroid carcinoma by suppressing the expression of
      high-mobility group A2, and therefore might provide a promising therapeutic
      target for patients with papillary thyroid carcinoma.

PMID- 29025377
TI  - 18F-FDG PET/CT in breast cancer: Evidence-based recommendations in initial
      staging.
AB  - Current guidelines do not systematically recommend 18F-FDG PET/CT for breast
      cancer staging; and the recommendations and level of evidence supporting its use
      in different groups of patients vary among guidelines. This review summarizes the
      evidence about the role of 18F-FDG PET/CT in breast cancer staging and the
      therapeutic and prognostic impact accumulated in the last decade. Other related
      aspects, such as the association of metabolic information with biology and
      prognosis are considered and evidence-based recommendations for the use of 18F
      FDG PET/CT in breast cancer staging are offered. We systematically searched
      MEDLINE for articles reporting studies with at least 30 patients related to
      clinical questions following the Problem/Population, Intervention, Comparison,
      and Outcome framework. We critically reviewed the selected articles and
      elaborated evidence tables structuring the summarized information into
      methodology, results, and limitations. The level of evidence and the grades of
      recommendation for the use of 18F-FDG PET/CT in different contexts are
      summarized. Level III evidence supports the use of 18F-FDG PET/CT for initial
      staging in patients with recently diagnosed breast cancer; the diagnostic and
      therapeutic impact of the 18F-FDG PET/CT findings is sufficient for a weak
      recommendation in this population. In patients with locally advanced breast
      cancer, level II evidence supports the use of 18F-FDG PET/CT for initial staging;
      the diagnostic and therapeutic impact of the 18F-FDG PET/CT findings is
      sufficient for a strong recommendation in this population. In patients with
      recently diagnosed breast cancer, the metabolic information from baseline 18F-FDG
      PET/CT is associated with tumor biology and has prognostic implications,
      supported by level II evidence. In conclusion, 18F-FDG PET/CT is not recommended
      for staging all patients with early breast cancer, although evidence of improved
      regional and systemic staging supports its use in locally advanced breast cancer.
      Baseline tumor glycolytic activity is associated with tumor biology and
      prognosis.

PMID- 29025378
TI  - Transfusion-Related Acute Lung Injury (TRALI) and Transfusion-Associated
      Circulatory Overload (TACO) in Liver Transplantation: A Case Report and Focused
      Review.
AB  - Liver transplantation (LT) is a complex procedure in a patient with multi-organ
      system dysfunction and coagulation defects. The surgical procedure involves
      dissection, major vessel manipulation, and pathophysiologic effects of graft
      storage and reperfusion. As a result, LT frequently involves significant
      hemorrhage. Subsequent massive transfusion carries high risk of transfusion
      associated complications. Transfusion-related acute lung injury (TRALI) and
      transfusion-associated circulatory overload (TACO) are the leading causes of
      transfusion associated mortality. In this case report and focused review, we
      present data that suggest that patients undergoing liver transplantation may be
      at higher risk for TRALI and TACO than the general population. Anesthesiologists
      can play a role in decreasing these risks by increasing recognition and reporting
      of TRALI and TACO, using point of care testing with thromboelastography to guide
      and decrease transfusion, and considering alternatives to traditional blood
      products like solvent/detergent plasma.

PMID- 29025379
TI  - Survival and Migration of Adipose-Derived Stem Cells Transplanted in the Injured
      Retina.
AB  - OBJECTIVES: Transplantation of stem cells is one of the approaches to treat
      retinal diseases. Our objective was to determine whether adipose-derived stem
      cell transplant can survive and migrate in the injured retina using a sodium
      iodate model for the pigmented retinal epithelium injury. MATERIALS AND METHODS:
      The adipose-derived stem cells were isolated from male albino Sprague-Dawley rats
      and labeled with DiI so as to track the transplants in the subretinal space.
      Retinal pigmented epithelium damage was induced by retro-orbital sinus sodium
      iodate injection (40 mg/kg) into albino Sprague-Dawley rats. Four weeks after
      transplantation, the eyeballs were fixed in 4% paraformaldehyde and cut with
      cryostat. The eyeballs were serially sectioned along the vertical meridian.
      Cryosections were from the full length of the retina and passing through the
      optic nerve head. The survival and migration of transplanted cells were assessed.
      RESULTS: Sodium iodate selectively destroyed the retinal pigmented epithelium
      layer. The transplanted cells incorporated into the retinal pigmented epithelium
      layer, perhaps differentiating into a retinal pigmented epithelium phenotype. The
      transplanted cells were located in the subretinal space; after 4 weeks, some were
      observed in the retinal pigmented epithelium layer. CONCLUSIONS: We found that
      adipose-derived stem cells survived for 4 weeks after transplantation and
      migrated into the retinal pigmented epithelium layer.

PMID- 29025380
TI  - Early Tracheostomy Reduces Time of Mechanical Ventilation in Respiratory High
      Risk Patients After Liver Transplant.
AB  - OBJECTIVES: Weaning from mechanical ventilation after liver transplant can be
      demanding. In selected cases, tracheostomy is helpful. The optimal timing for
      tracheostomy in ventilator-dependent liver transplant recipients is not well
      known. MATERIALS AND METHODS: We retrospectively analyzed data of 447 patients
      who had undergone liver transplant in our hospital. Thirty-nine patients who had
      high risk of prolonged mechanical ventilation according to the Respiratory Risk
      Score were identified from 95 patients who received tracheostomy after liver
      transplant. RESULTS: When compared with tracheostomy performed > 3 days after
      transplant, early tracheostomy (<= 3 days) had a higher likelihood of a brief
      duration of mechanical ventilation (62.5% vs 9.7%; P = .001). Accordingly, time
      spent in an intensive care unit was shorter with early tracheostomy. CONCLUSIONS:
      This study provides a retrospective analysis of a small study cohort; therefore,
      validation of our findings requires a prospective randomized multicenter study on
      early tracheostomy in respiratory high-risk liver transplant recipients.

PMID- 29025381
TI  - Adenovirus Infection as a Cause of Fever of Unknown Origin and Allograft
      Dysfunction in a Kidney Transplant Recipient.
AB  - With the recent introduction of more potent modern immunosuppressive regimens in
      solid-organ transplant, new types of viral infections such as adenovirus are
      emerging as a potential cause for graft dysfunction and loss. We report a case of
      41-year-old male patient with end-stage renal disease from recurrent kidney
      stones who underwent kidney transplant from a deceased 12-year-old female donor.
      He developed adenoviral infection with acute cystitis, microscopic hematuria, and
      necrotizing interstitial nephritis associated with graft dysfunction within the
      first month of the postoperative period. Diagnosis was made by graft biopsy that
      showed more than 60% necrosis with tubulointerstitial hemorrhage, thrombotic
      microangiopathy, and histologic features suggestive of viral infection with
      negative Cytomegalovirus and polyomavirus stains in the graft and elevated
      adenovirus PCR in the blood. Simultaneously, the patient had very low absolute
      total lymphocyte count of 70 cells/MUL during which he received supratherapeutic
      tacrolimus at whole blood trough levels and mycophenolate mofetil. This prompted
      the tapering of immunosuppression and the discontinuation of all antimicrobial
      drugs. Within a 2-week period, the immune reconstitution was sufficient for the
      clearance of the infection and the subsequent gradual recovery of graft function.

PMID- 29025382
TI  - Biliary Complications in Recipients of Living-Donor Liver Transplant: A Single
      Center Review of 120 Patients.
AB  - OBJECTIVES: Biliary complications are common after living-donor liver transplant.
      This retrospective study reviewed our experience with biliary complications in
      recipients of living-donor liver transplant. MATERIALS AND METHODS: Over our 9
      year study period, 120 patients underwent living-donor liver transplant. Patients
      were divided into 2 groups, with group A having biliary complications and group B
      without biliary complications. Both groups were compared, and different treatment
      modalities for biliary complications were evaluated. RESULTS: Group A included 45
      patients (37.5%), whereas group B included 75 patients (62.5%). Biliary
      complications included bile leak in 17 patients (14.2%), biliary stricture in 11
      patients (9.2%), combined biliary stricture with bile leak in 15 patients
      (12.5%), and sphincter of Oddi dysfunction and cholangitis in 1 patient each
      (0.8%). Cold ischemia time was significantly longer in group A (P = .002).
      External biliary drainage was less frequently used in group A (P = .031).
      Technical success rates of endoscopic biliary drainage and percutaneous
      transhepatic biliary drainage were 68.3% and 41.7%. Survival rate following
      relaparotomy for biliary complications was 62.5%. CONCLUSIONS: Graft ischemia is
      an important risk factor for biliary complications. Bile leaks can predispose to
      anastomotic strictures. The use of external biliary drainage seems to reduce the
      incidence of biliary complications. Endoscopic and percutaneous trans-hepatic
      approaches can successfully treat more than two-thirds of biliary complications.
      Relaparotomy can improve survival outcomes and is usually reserved for patients
      with intractable biliary complications.

PMID- 29025384
TI  - Renal Transplant Failure Due to Infiltrating Kaposi Sarcoma.
AB  - Kaposi sarcoma is one of the most common malignancies seen during the
      posttransplant period, and it usually manifests in its cutaneous form. Renal
      transplant involvement is rare, whereas renal transplant parenchymal involvement
      causing transplant dysfunction is exceptionally rare. We report a case of
      visceral Kaposi sarcoma that led to renal transplant failure due to neoplastic
      infiltration of the renal allograft.

PMID- 29025383
TI  - Repair of Bile Duct Injury With Autologous Vein Graft and Stent.
AB  - OBJECTIVES: We investigated the effects of autologous vein transplant on bile
      duct injury repair, through observation of the hepatic and biliary system tissue
      morphology changes and animal survival after bile duct injury repair. MATERIALS
      AND METHODS: Rabbits were equally divided into groups. Group A had
      cholecystectomy and common bile duct resection (length of 0.5 cm), transplant of
      an autologous vein (length of 0.5 cm), and stent implant. Group B had
      cholecystectomy and common bile duct resection (length of 1.0 cm), transplant of
      an autologous vein (length of 1.0 cm), and stent implant. The third group (group
      C) had cholecystectomy only. RESULTS: Two rabbits died in group A and group B;
      all experimental animals from group C survived. Regarding liver biochemical
      indexes at preoperative week 1, at postoperative month 1, and at postoperative
      month 3, we found no significant differences (paired t test, P > .05). Liver
      biochemical indexes between groups were also not significantly different (P >
      .05). At month 3, postoperative liver pathology of experimental animals showed no
      significant changes and no cholestasis; biliary epithelial cells were seen in the
      transplant vascular. CONCLUSIONS: We conclude that autologous vein graft can
      effectively repair bile duct injury for a short coloboma.

PMID- 29025385
TI  - The Impact of Preoperative Variables on Intraoperative Blood Loss and Transfusion
      Requirements During Orthotopic Liver Transplant.
AB  - OBJECTIVES: Liver transplant traditionally and potentially is associated with the
      risk of massive blood loss and transfusion, which can adversely affect transplant
      outcomes. Many variables influence the amount of bleeding, and these can be
      categorized as patient related, surgery related, and graft related. We aimed to
      assess the effects of these variables on the amount of bleeding and transfusion
      during liver transplant; predicting the risk of massive blood loss can help
      transplant teams to select and manage patients more effectively. MATERIALS AND
      METHODS: We retrospectively studied 754 patients who underwent liver transplant
      from 2013 to 2016 and analyzed more than 20 variables that could influence the
      volume of blood loss and packed cell transfusion. RESULTS: We found that at least
      4 variables are strongly and independently correlated with blood loss volume:
      age, Model for End-Stage Liver Disease score, warm ischemia time, and total
      bilirubin. Furthermore, intraoperative blood loss had a weak but clinically
      important correlation with the underlying disease (ie, the cause of liver
      cirrhosis). Some variables, including international normalized ratio, platelet
      count, albumin, serum urea nitrogen, creatinine level, sodium level, and the
      amount of ascites, could be considered as 'dependent' and weak predictors of
      massive blood loss. Sex of patient, cold ischemia time, surgery technique, and
      history of previous abdominal surgery were not correlated with the amount of
      bleeding. CONCLUSIONS: With the use of the variables identified, we can properly
      select patients and surgical teams and promptly use modalities for decreasing and
      managing blood loss.

PMID- 29025386
TI  - Preoperative Cardiac Risk Assessment in Renal Transplant Recipients: A Single
      Center Experience.
AB  - OBJECTIVES: Cardiovascular disease is the major cause of morbidity and mortality
      in patients on renal replacement therapy and in kidney transplant recipients.
      There are no specific recommendations for preoperative cardiac risk assessment
      before renal transplant. The aim of our study was to analyze preoperative cardiac
      test frequencies, test results, patient characteristics, and relations between
      cardiac stress test results and severe coronary artery disease. MATERIALS AND
      METHODS: We retrospectively examined patients who underwent renal transplant
      between December 2011 and December 2016 in our hospital (Ankara, Turkey). Our
      study group included 216 patients. All patients had preoperative
      echocardiography. We recorded results of exercise stress tests, myocardial
      perfusion scintigraphy, and coronary angiography. For all patients, preoperative
      complete blood cell count, creatinine, high-density lipoprotein, triglycerides,
      low-density lipoprotein, and red cell distribution width values were obtained and
      recorded. RESULTS: We classified patient groups according to presence or absence
      of severe coronary artery disease. Fourteen of 66 patients had severe coronary
      artery disease. In univariate analyses, age, having a history of familial
      coronary artery disease, diabetes mellitus, presence of coronary artery disease,
      and triglyceride levels were risk factors for severe coronary artery disease. In
      multivariate analysis, diabetes mellitus, presence of coronary artery disease,
      and having a history of familial coronary artery disease were statistically
      significant. CONCLUSIONS: Renal transplant recipients are a special patient
      population, and there must be specific suggestions for this population. If
      patients present with more than 1 risk factor, a stress test should be performed
      to evaluate cardiovascular risk. In some patients, especially those whose risk
      factors include prior cardiovascular disease or diabetes mellitus, stress tests
      should be skipped and patients should directly undergo coronary angiography to
      look for severe coronary artery disease.

PMID- 29025387
TI  - In Vitro Study on Influences of UGT1A8 Gene Polymorphisms on Mycophenolate
      Mofetil Metabolism.
AB  - OBJECTIVES: Mycophenolate mofetil is a first-line drug after organ transplant,
      but there are differences in metabolism of mycophenolate mofetil among
      individuals. The UDP glucuronosyltransferase enzyme is the key metabolic enzyme
      for mycophenolate mofetil, and UGT1A8 gene polymorphisms may affect the
      elimination of mycophenolate mofetil in patients. Here, we conducted an in vitro
      study to explore the relation between UGT1A8 gene polymorphisms and mycophenolate
      mofetil metabolism. MATERIALS AND METHODS: Five mutant loci overexpression
      vectors (UGT1A8 128C>T, 157C>A, 431C>T, 518C>G, and 830G>A) were constructed by
      genetic recombination and site-directed mutagenesis. We used Lipo2000
      (Invitrogen, Carlsbad, CA, USA) to transfect the vectors into HEK293 cells.
      Mycophenolic acid, the active ingredient of mycophenolate mofetil, was added to
      different groups of cells. We then used the liquid chromatography tandem-mass
      spectrometry technique to detect production of the metabolite 7-O-mycophenolic
      acid glucuronide and to evaluate activity of the UDP glucuronosyltransferase
      enzyme in cells with different overexpression vectors. RESULTS: Mutations of
      UGT1A8 157C>A and 518C>G vectors can lead to increased activity of UDP
      glucuronosyltransferase enzymes and increased production of the 7-O-mycophenolic
      acid glucuronide metabolite, which showed 116% (P < .001) and 107% (P = .0191)
      production changes of 157C>A and 518C>G mutations, respectively, relative to wild
      type UGT1A8. However, mutations of UGT1A8 431C>T and 830G>A loci resulted in
      decreased activity of UDP glucuronosyltransferase enzymes and decreased
      production of the metabolite, respectively showing 62.9% (P < .001) and 9.05% (P
      < .001) activity relative to wild-type UGT1A8. UGT1A8 128C>T had little effect on
      enzyme activity, with 96.8% activity relative to wild-type UGT1A8 (P = .0569).
      CONCLUSIONS: Our results showed that UGT1A8 gene polymorphisms can affect the
      activity of UDP glucuronosyltransferase enzyme, which may influence the
      elimination of mycophenolate mofetil in different patients.

PMID- 29025388
TI  - Editorial: Corticotropin Releasing Factor (CRF) and its Receptors: From Structure
      to Function in Health and Disease (Part I).

PMID- 29025390
TI  - Partitioning of functional gene expression data using principal points.
AB  - BACKGROUND: DNA microarrays offer motivation and hope for the simultaneous study
      of variations in multiple genes. Gene expression is a temporal process that
      allows variations in expression levels with a characterized gene function over a
      period of time. Temporal gene expression curves can be treated as functional data
      since they are considered as independent realizations of a stochastic process.
      This process requires appropriate models to identify patterns of gene functions.
      The partitioning of the functional data can find homogeneous subgroups of
      entities for the massive genes within the inherent biological networks. Therefor
      it can be a useful technique for the analysis of time-course gene expression
      data. We propose a new self-consistent partitioning method of functional
      coefficients for individual expression profiles based on the orthonormal basis
      system. RESULTS: A principal points based functional partitioning method is
      proposed for time-course gene expression data. The method explores the
      relationship between genes using Legendre coefficients as principal points to
      extract the features of gene functions. Our proposed method provides high
      connectivity in connectedness after clustering for simulated data and finds a
      significant subsets of genes with the increased connectivity. Our approach has
      comparative advantages that fewer coefficients are used from the functional data
      and self-consistency of principal points for partitioning. As real data
      applications, we are able to find partitioned genes through the gene expressions
      found in budding yeast data and Escherichia coli data. CONCLUSIONS: The proposed
      method benefitted from the use of principal points, dimension reduction, and
      choice of orthogonal basis system as well as provides appropriately connected
      genes in the resulting subsets. We illustrate our method by applying with each
      set of cell-cycle-regulated time-course yeast genes and E. coli genes. The
      proposed method is able to identify highly connected genes and to explore the
      complex dynamics of biological systems in functional genomics.

PMID- 29025389
TI  - Chromatin states responsible for the regulation of differentially expressed genes
      under 60Co~gamma ray radiation in rice.
AB  - BACKGROUND: The role of histone modifications in the DNA damage response has been
      extensively studied in non-plant systems, including mammals and yeast. However,
      there is a lack of detailed evidence showing how chromatin dynamics, either an
      individual mark or combined chromatin states, participate in regulating
      differentially expressed genes in the plant DNA damage response. RESULTS: In this
      study, we used RNA-seq and ChIP-seq to show that differentially expressed genes
      (DEGs), in response to ionizing radiation (IR), might be involved in different
      pathways responsible for the DNA damage response. Moreover, chromatin structures
      associated with promoters, exons and intergenic regions are significantly
      affected by IR. Most importantly, either an individual mark or a certain
      chromatin state was found to be highly correlated with the expression of up
      regulated genes. In contrast, only the chromatin states, as opposed to any
      individual marks tested, are related to the expression of the down-regulated
      genes. CONCLUSIONS: Our findings demonstrate that IR-related DEGs are modulated
      by distinct epigenetic mechanisms. Either chromatin states or distinct histone
      dynamics may act sequentially or in combination in regulating up-regulated genes,
      but the complex chromatin structure is mainly responsible for the expression of
      down-regulated genes. Thus, this study provides new insights into how up- and
      down-regulated genes are epigenetically regulated at the chromatin levels,
      thereby helping us to understand distinct epigenetic mechanisms that function in
      the plant DNA damage response.

PMID- 29025391
TI  - Identification of putative markers linked to grain plumpness in rice (Oryza
      sativa L.) via association mapping.
AB  - BACKGROUND: Poor grain plumpness (GP) is one of the main constraints to reaching
      the yield potential of hybrid rice. RESULTS: In this study, the GP of 177 rice
      varieties was investigated in three locations across 2 years. By combining the
      genotype data of 261 simple sequence repeat (SSR) markers, association mapping
      was conducted to identify the marker-GP association loci. Among 31 marker-GP
      association loci detected in two or more environments and determined using
      general linear model (GLM) analyses, seven association loci were also detected
      using mixed linear model (MLM) analyses. The seven common loci detected by the
      two analytical methods were located on chromosomes 2, 3 (2), 7, 8 and 12 (2) and
      explained 7.24~22.28% of the variance. Of these 7 association loci, five markers
      linked to GP were newly detected: RM5340 on Chr2, RM5480 and RM148 on Chr3,
      RM1235 on Chr8, and RM5479 on Chr12. CONCLUSIONS: Five marker-GP association loci
      were newly detected using both the GLM and MLM analytical methods. Elite allele
      RM505-170 bp had the highest average phenotypic effect on increasing the GP, and
      the typical carrier variety was 'Maozitou'. Based on the distribution of the
      elite alleles among the carrier varieties, the top 10 parental combinations for
      improving the GP in rice via cross-breeding were predicted.

PMID- 29025392
TI  - Co-founding ant queens prevent disease by performing prophylactic undertaking
      behaviour.
AB  - BACKGROUND: Social insects form densely crowded societies in environments with
      high pathogen loads, but have evolved collective defences that mitigate the
      impact of disease. However, colony-founding queens lack this protection and
      suffer high rates of mortality. The impact of pathogens may be exacerbated in
      species where queens found colonies together, as healthy individuals may contract
      pathogens from infectious co-founders. Therefore, we tested whether ant queens
      avoid founding colonies with pathogen-exposed conspecifics and how they might
      limit disease transmission from infectious individuals. RESULTS: Using Lasius
      niger queens and a naturally infecting fungal pathogen Metarhizium brunneum, we
      observed that queens were equally likely to found colonies with another pathogen
      exposed or sham-treated queen. However, when one queen died, the surviving
      individual performed biting, burial and removal of the corpse. These undertaking
      behaviours were performed prophylactically, i.e. targeted equally towards non
      infected and infected corpses, as well as carried out before infected corpses
      became infectious. Biting and burial reduced the risk of the queens contracting
      and dying from disease from an infectious corpse of a dead co-foundress.
      CONCLUSIONS: We show that co-founding ant queens express undertaking behaviours
      that, in mature colonies, are performed exclusively by workers. Such infection
      avoidance behaviours act before the queens can contract the disease and will
      therefore improve the overall chance of colony founding success in ant queens.

PMID- 29025393
TI  - Molecular basis of African yam domestication: analyses of selection point to root
      development, starch biosynthesis, and photosynthesis related genes.
AB  - BACKGROUND: After cereals, root and tuber crops are the main source of starch in
      the human diet. Starch biosynthesis was certainly a significant target for
      selection during the domestication of these crops. But domestication of these
      root and tubers crops is also associated with gigantism of storage organs and
      changes of habitat. RESULTS: We studied here, the molecular basis of
      domestication in African yam, Dioscorea rotundata. The genomic diversity in the
      cultivated species is roughly 30% less important than its wild relatives. Two
      percent of all the genes studied showed evidences of selection. Two genes
      associated with the earliest stages of starch biosynthesis and storage, the
      sucrose synthase 4 and the sucrose-phosphate synthase 1 showed evidence of
      selection. An adventitious root development gene, a SCARECROW-LIKE gene was also
      selected during yam domestication. Significant selection for genes associated
      with photosynthesis and phototropism were associated with wild to cultivated
      change of habitat. If the wild species grow as vines in the shade of their tree
      tutors, cultivated yam grows in full light in open fields. CONCLUSIONS: Major
      rewiring of aerial development and adaptation for efficient photosynthesis in
      full light characterized yam domestication.

PMID- 29025394
TI  - Prediction of Human Phenotype Ontology terms by means of hierarchical ensemble
      methods.
AB  - BACKGROUND: The prediction of human gene-abnormal phenotype associations is a
      fundamental step toward the discovery of novel genes associated with human
      disorders, especially when no genes are known to be associated with a specific
      disease. In this context the Human Phenotype Ontology (HPO) provides a standard
      categorization of the abnormalities associated with human diseases. While the
      problem of the prediction of gene-disease associations has been widely
      investigated, the related problem of gene-phenotypic feature (i.e., HPO term)
      associations has been largely overlooked, even if for most human genes no HPO
      term associations are known and despite the increasing application of the HPO to
      relevant medical problems. Moreover most of the methods proposed in literature
      are not able to capture the hierarchical relationships between HPO terms, thus
      resulting in inconsistent and relatively inaccurate predictions. RESULTS: We
      present two hierarchical ensemble methods that we formally prove to provide
      biologically consistent predictions according to the hierarchical structure of
      the HPO. The modular structure of the proposed methods, that consists in a "flat"
      learning first step and a hierarchical combination of the predictions in the
      second step, allows the predictions of virtually any flat learning method to be
      enhanced. The experimental results show that hierarchical ensemble methods are
      able to predict novel associations between genes and abnormal phenotypes with
      results that are competitive with state-of-the-art algorithms and with a
      significant reduction of the computational complexity. CONCLUSIONS: Hierarchical
      ensembles are efficient computational methods that guarantee biologically
      meaningful predictions that obey the true path rule, and can be used as a tool to
      improve and make consistent the HPO terms predictions starting from virtually any
      flat learning method. The implementation of the proposed methods is available as
      an R package from the CRAN repository.

PMID- 29025396
TI  - A description of the gross pathology of drowning and other causes of mortality in
      seabirds.
AB  - BACKGROUND: Mortality of seabirds due to anthropogenic causes, especially
      entrapment in fishing gear, is a matter of increasing international concern. This
      study aimed at characterising the gross pathology of seabirds that drowned in
      fishing nets and comparing it with that in other common causes of mortality.
      RESULTS: Post-mortem examinations were performed on 103 common guillemots, 32
      razorbills, 37 shags and 5 great northern divers found stranded in Cornwall
      during 1981-2016. Pathology in birds that died in confirmed incidents of drowning
      in fishing nets (n = 95) was compared with that in cases of suspected drowning (n
      = 6), oil (n = 53) and polyisobutylene (PIB) (n = 3) pollution, adverse weather
      (n = 6) and stranding of unknown cause (14). The majority of drowned birds were
      in good nutritional state, freshly dead and approximately 50% had freshly
      ingested fish in their proximal gut. Principle lesions were: gross distention of
      the heart and major veins with dark blood, intensely congested, swollen and
      oedematous lungs which released white frothy fluid when excised, watery fluid in
      the air sacs that ranged from clear to deep red depending on state of carcase
      preservation. PIB-affected birds were in good nutritional state; their pathology
      was largely consistent with that in confirmed drowning cases; it is likely that
      drowning was the ultimate cause of death. Birds affected by oil, adverse weather
      or that stranded due to unknown cause were all in poor or emaciated condition,
      the mean body mass of the guillemots and razorbills being, respectively, 53 and
      57% of those that drowned. They had little or no food in their alimentary tracts
      and many showed evidence of enteric inflammation, haemorrhage and ulceration.
      None had fluid in their air sacs and none showed significant cardio-respiratory
      system lesions. CONCLUSIONS: Drowned birds consistently showed a distinctive set
      of gross pathological lesions. When combined with contemporaneous observations,
      the pathology may be sufficient to permit a diagnosis of drowning, especially
      where a batch of freshly dead birds are examined. The observations in this study
      are likely to be of value when investigating stranding incidents, particularly
      where it is suspected that legislation aimed at protecting seabirds is not being
      complied with.

PMID- 29025395
TI  - Proposed risk factors for infection with multidrug-resistant pathogens in
      hemodialysis patients hospitalized with pneumonia.
AB  - BACKGROUND: In patients with hemodialysis-associated pneumonia (HDAP),
      information on both microbiologic features and antimicrobial strategies is
      limited. The aim of this study is to investigate predictive factors of infection
      with multidrug-resistant (MDR) pathogens in HDAP patients. METHODS: This was a
      multicenter, retrospective, and observational study. Enrolled patients were
      classified into MDR or non-MDR pathogens groups according to culture results. We
      examined risk factors of infection with MDR pathogens and created a decision
      support tool using these risk factors. RESULTS: MDR pathogens were identified in
      24 (22.8%) out of a total of 105 HDAP patients. The most common MDR pathogens
      were methicillin-resistant Staphylococcus aureus (10 patients, 9.5%) and the
      isolation rate of Pseudomonas aeruginosa was 6.6%. Logistic regression showed two
      variables were associated with the isolation of MDR pathogens: recent
      hospitalization (adjusted odds ratio [OR]: 2.951, 95% confidence interval [CI]:
      1.022-8.518) and PSI (Pneumonia Severity Index) score (adjusted OR: 1.023, 95%
      CI: 1.005-1.041). The optimal cut-off value for PSI score using a receiver
      operating characteristic curve analysis was 147. According to the presence of 0,
      1, or 2 of the identified risk factors, the prevalence of MDR pathogens was 7.6,
      28.2 and 64.2%, respectively (p < 0.001 for trend). The area under the curve of
      the prediction tool was 0.764 (95% CI: 0.652-0.875). CONCLUSIONS: We demonstrated
      that recent hospitalization and PSI > 147 are risk factors of infection with MDR
      pathogens in HDAP patients. This simple proposed tool would facilitate more
      accurate identification of MDR pathogens in these patients.

PMID- 29025397
TI  - A qualitative study of patient education needs for hip and knee replacement.
AB  - BACKGROUND: Quality health information is key to patient engagement, self
      management and an enhanced healthcare experience. There is strong evidence to
      support involving patients and their families in the development and evaluation
      of health-related educational material. These factors were the impetus for our
      high volume joint replacement centre to undertake a qualitative study to elicit
      patient experiences to inform the development of effective strategies and
      education along the care continuum for hip and knee replacement. METHODS:
      Purposively selected patients from postoperative follow-up clinics were recruited
      to participate in a focus group or telephone interview. We developed a semi
      structured interview guide that addressed four specific aspects of the patient's
      experience with educational material: pre-surgery, hospital stay, recovery period
      and future recommendations. The focus groups and interviews continued to the
      point of saturation and were audio-recorded and transcribed verbatim. Interview
      transcripts were coded and then inductively organized into larger categories
      using thematic analysis. RESULTS: Six focus groups and seven telephone interviews
      were conducted, totalling 32 participants. One of the key themes that emerged was
      a need for more education concerning pain management post-operatively;
      specifically, patients wanted more information on expected levels of pain, pain
      medication usage, management of side effects and guidelines for weaning off the
      medication. There was surprising variability in patients' descriptions of their
      pre-surgery, surgery and recovery experiences. These corresponded to an equally
      diverse range of preferences for educational content, delivery and timing. Many
      patients reported using the web while others preferred traditional formats for
      information delivery. There was some interest in receiving education using mobile
      technology. CONCLUSIONS: Our findings validate the importance of multi-modal
      patient education tailored to individual preferences and experiences, which may
      differ according to such characteristics as gender and age. The gap in pain
      management information is a critical finding for healthcare providers working
      with patients undergoing joint replacement. Developing pain management education
      in different formats that addresses frequently asked questions will enhance
      patient engagement and, their overall experience and recovery.

PMID- 29025398
TI  - Should community health workers offer support healthcare services to survivors of
      sexual violence? a systematic review.
AB  - BACKGROUND: Sexual violence is widespread, yet relatively few survivors receive
      healthcare or complete treatment. In low and middle-income countries, community
      health workers (CHWs) have the potential to provide support services to large
      numbers of survivors. The aim of this review was to document the role of CHWs in
      sexual violence services. We aimed to: 1) describe existing models of CHWs
      services including characteristics of CHWs, services delivered and populations
      served; 2) explore acceptability of CHWs' services to survivors and feasibility
      of delivering such services; and 3) document the benefits and challenges of CHW
      provided sexual violence services. METHODS: Quantitative and qualitative studies
      reporting on CHWs and other community-level paraprofessional volunteer services
      for sexual violence were eligible for inclusion. CHWs and sexual violence were
      defined according to WHO criteria. The review was conducted according to the
      Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.
      Quality of included studies was assessed using two quality assessment tools for
      quantitative, and, the methodology checklist by the National Institute for Health
      and Clinical Excellence for qualitative studies. Data were extracted and analysed
      separately for quantitative and qualitative studies and results integrated using
      a framework approach. RESULTS: Seven studies conducted in six countries
      (Democratic Republic of Congo, Rwanda, Burma, United States of America, Scotland,
      Israel) met the inclusion criteria. Different models of care had diverse CHWs
      roles including awareness creation, identifying, educating and building
      relationships with survivors, psychosocial support and follow up. Although
      sociocultural factors may influence CHWs' performance and willingness of
      survivors to use their services, studies often did not report on CHWs
      characteristics. Few studies assessed acceptability of CHWs' to survivors or
      feasibility of delivery of services. However, participants mentioned a range of
      benefits including decreased incidence of violence, CHWs being trusted,
      approachable, non-judgmental and compassionate. Challenges identified were high
      workload, confidentiality issues and community norms influencing performance.
      CONCLUSIONS: There is a dearth of research on CHWs services for sexual violence.
      Findings suggest that involving CHWs may be beneficial, but potential challenges
      and harms related to CHW-provided services exist. No different models of CHW
      provided care have been robustly evaluated for effects on patient outcomes.
      Further research to establish survivors' views on these services, and, their
      effectiveness is desperately needed.

PMID- 29025400
TI  - Increased amputation risk with canagliflozin treatment: behind the large
      cardiovascular benefit?
AB  - A growing body of evidence suggests that sodium-glucose cotransporter 2 (SGLT2)
      inhibitors appear to be a powerful option to improve the cardiovascular (CV)
      prognosis in high CV-risk patients with type 2 diabetes. Despite a significant
      reduction in major adverse CV events with SGLT2 inhibitor treatment, however, an
      unexpected increased risk of amputation was observed in the CANVAS program and
      the subsequent pharmacovigilance analysis. Although the underlying mechanisms are
      currently unknown, because amputation has a large negative impact on patient
      clinical course, clinicians want to know the exact reason for the increased
      amputation in the canagliflozin treatment. We herein discuss a need to elucidate
      the actual reasons with more appropriate statistical consideration, taking into
      account individual clinical course potentially involved in the diabetes-related
      amputation. Decreases in the hardendpoints by canagliflozin might result in an
      alternate increase in the other diabetes-related complications, including
      amputation. In addition, if amputation occurred after stopping canagliflozin, the
      incidence might be caused by worsened glycemic control and a decrease in
      hematocrit, accompanied by a subsequent worsening of diabetic foot disease. More
      detailed approach considering individual clinical course potentially involved in
      the amputation, would help to further unravel the cause for suspected risk of
      amputation with canagliflozin.

PMID- 29025399
TI  - Plasmodium falciparum EPCR-binding PfEMP1 expression increases with malaria
      disease severity and is elevated in retinopathy negative cerebral malaria.
AB  - BACKGROUND: Expression of group A and the A-like subset of group B Plasmodium
      falciparum erythrocyte membrane protein 1 (PfEMP1) is associated with severe
      malaria (SM). The diversity of var sequences combined with the challenges of
      distinct classification of patient pathologies has made studying the role of
      distinct PfEMP1 variants on malaria disease severity challenging. The application
      of retinopathy in the recent years has provided a further method to clinically
      evaluate children with cerebral malaria (CM). The question of whether children
      with clinical CM but no retinopathy represent a completely different disease
      process or a subgroup within the spectrum of CM remains an important question in
      malaria. In the current study, we use newly designed primer sets with the best
      coverage to date in a large cohort of children with SM to determine the role of
      var genes in malaria disease severity and especially CM as discriminated by
      retinopathy. METHODS: We performed qRT-PCR targeting the different subsets of
      these var genes on samples from Ugandan children with CM (n = 98, of whom 50 had
      malarial retinopathy [RP] and 47 did not [RN]), severe malarial anemia (SMA, n =
      47), and asymptomatic parasitemia (AP, n = 14). The primers used in this study
      were designed based on var sequences from 226 Illumina whole genome sequenced P.
      falciparum field isolates. RESULTS: Increasing severity of illness was associated
      with increasing levels of endothelial protein C receptor (EPCR)-binding PfEMP1.
      EPCR-binding PfEMP1 transcript levels were highest in children with combined CM
      and SMA and then decreased by level of disease severity: RP CM > RN CM > SMA >
      AP. CONCLUSIONS: The study findings indicate that PfEMP1 binding to EPCR is
      important in the pathogenesis of SM, including RN CM, and suggest that increased
      expression of EPCR-binding PfEMP1 is associated with progressively more severe
      disease. Agents that block EPCR-binding of PfEMP1 could provide novel
      interventions to prevent or decrease disease severity in malaria.

PMID- 29025401
TI  - Headache symptoms from migraine patients with and without aura through structure
      validated self-reports.
AB  - BACKGROUND: Headache symptoms self-reported by migraine patients are largely
      congruent with the clinician-used diagnostic criteria, but not always so.
      Patients' self-reports of headache symptoms might offer additional clues to
      characterize migraine with (MA) and without (MO) aura more precisely. METHODS:
      Firstly, we invited 324 participants with a life-long headache attack to answer
      an item-matrix measuring symptoms of primary headaches, then we performed both
      exploratory and confirmatory factor analyses to their answers and refined a
      headache symptom questionnaire. Secondly, we applied this questionnaire to 28 MA
      and 52 MO patients. RESULTS: In participants with a life-long headache, we
      refined a 27-item, structure-validated headache symptom questionnaire, with four
      factors (scales) namely the Somatic /Aura Symptoms, Gastrointestinal and
      Autonomic Symptoms, Tightness and Location Features, and Prodromal/Aggravating
      Symptoms. Further, we found that MA patients reported higher than did MO patients
      on the Somatic/Aura Symptoms and Tightness and Location Features scales.
      CONCLUSIONS: Compared to MO, MA was conferred with more prominent tightness and
      location features besides its higher somatic or aura symptoms. Patients' self
      reports of headache symptoms might offer more clues to distinguish two types of
      migraine besides their clinician-defined criteria.

PMID- 29025402
TI  - Rates of, and risk factors for, septic arthritis in patients with invasive
      pneumococcal disease: prospective cohort study.
AB  - BACKGROUND: There are many case reports of septic arthritis complicating invasive
      pneumococcal disease (IPD); however, no study has compared patients with IPD with
      septic arthritis to those who didn't develop septic arthritis Thus, we aimed to
      determine the rates of, and risk factors for, septic arthritis in patients with
      invasive pneumococcal disease (IPD). METHODS: Socio-demographic, clinical, and
      serological data were captured on all patients with IPD in Northern Alberta,
      Canada from 2000 to 2014. Septic arthritis was identified by attending
      physicians. Descriptive statistics and multivariate analyses were used to compare
      characteristics of those with septic arthritis and IPD to those who did not.
      RESULTS: Septic arthritis developed in 51 of 3251 (1.6%) of patients with IPD.
      Inability to walk independently, male sex, and underlying joint disease were risk
      factors for developing septic arthritis in patients with IPD. Capsular serotypes
      22 and 12F were more common in patients with septic arthritis than those without.
      CONCLUSIONS: In patients with IPD, septic arthritis is uncommon. Certain risk
      factors such as walking with or without assistance and underlying joint disease
      make biological sense as damaged joints are more likely to be infected in the
      presence of bacteremia. TRIAL REGISTRATION: Not applicable.

PMID- 29025403
TI  - Tuberculosis among older adults in Zambia: burden and characteristics among a
      neglected group.
AB  - BACKGROUND: The 2010 Global Burden of Disease estimates show that 57% of all TB
      deaths globally occurred among adults older than 50 years of age. Few studies
      document the TB burden among older adults in Southern Africa. We focused on
      adults older than 55 years to assess the relative TB burden and associated
      demographic factors. METHODS: A cross sectional nationally representative TB
      prevalence survey conducted of Zambian residents aged 15 years and above from 66
      clusters across all the 10 provinces of Zambia. Evaluation included testing for
      TB as well as an in-depth questionnaire. We compared survey data for those aged
      55 and older to those aged 15-54 years. Survey results were also compared with
      2013 routinely collected programmatic notification data to generate future
      hypotheses regarding active and passive case finding. RESULTS: Among older adults
      with TB, 30/ 54 (55.6%) were male, 3/27 (11.1%) were HIV infected and 35/54
      (64.8%) lived in rural areas. TB prevalence was higher in those aged >=55 (0.7%)
      than in the 15-54 age group (0.5%). Males had higher rates of TB across both age
      groups with 0.7% (15-54) and 1.0% (>=55) compared with females 0.4% (15-54) and
      0.6% (>=55). In rural areas, the prevalence of TB was significantly higher among
      older than younger adults (0.7% vs 0.3%), while the HIV infection rate was among
      TB patients was lower (11.1% vs 30.8%). The prevalence survey detected TB in
      54/7484 (0.7%) of older adults compared to 3619/723,000 (0.5%) reported in 2013
      programmatic data. CONCLUSION: High TB rates among older adults in TB endemic
      areas justify consideration of active TB case finding and prevention strategies.

PMID- 29025404
TI  - Working people with type 1 diabetes in the Finnish population.
AB  - BACKGROUND: The incidence of type 1 diabetes is increasing worldwide. Since so
      little is known about work life of individuals with type 1 diabetes, we examined
      incidence and prevalence trends of type 1 diabetes among working-aged Finns. We
      also investigated the employment rate and how workers with type 1 diabetes
      perceive their health and work ability, and their intended retirement age.
      METHODS: We analyzed changes in the incidence, prevalence, and employment rate
      using nationwide multi-register-based FinDM data, and estimated a Self-Rated
      Health, Work Ability Score, and inquired about retirement intentions of 767
      working individuals with type 1 diabetes in a cross-sectional survey. All
      estimates were compared to the corresponding data of the Finnish general
      population. RESULTS: The average annual age-standardized incidence rate of type 1
      diabetes among men aged 18-39 was 29 per 100,000/year; the incidence rate has
      increased by 33% from 1992 to 2007. Among women, the incidence remained at 16 per
      100,000/year. Among working-aged (18-64) people, the age-standardized prevalence
      of type 1 diabetes increased by 39% among women and 33% among men. Two out of
      every three working aged individuals with type 1 diabetes were in the labor
      force; this is about 10% lower than in the Finnish population. The average age
      standardized employment rate among those individuals with type 1 diabetes
      belonging to the labor force was 82%, compared to 84% in the general population.
      Working individuals with type 1 diabetes rated their health and work ability as
      being slightly lower than the general working population, but nonetheless, there
      were no significant differences in retirement intentions. CONCLUSIONS: Between
      1992 and 2007, the number of working-aged people and workers with type 1 diabetes
      increased by 35%. Most workers with type 1 diabetes manage as well at work as the
      general population. Special attention should be paid to workers with type 1
      diabetes when they are diagnosed and/or report moderate or poor work ability.

PMID- 29025405
TI  - The anti-inflammatory function of HDL is impaired in type 2 diabetes: role of
      hyperglycemia, paraoxonase-1 and low grade inflammation.
AB  - BACKGROUND: Functional properties of high density lipoproteins (HDL) are
      increasingly recognized to play a physiological role in atheroprotection. Type 2
      diabetes mellitus (T2DM) is characterized by low HDL cholesterol, but the effect
      of chronic hyperglycemia on the anti-inflammatory capacity of HDL, a metric of
      HDL function, is unclear. Therefore, the aim of the present study was to
      establish the impact of T2DM on the HDL anti-inflammatory capacity, taking
      paraoxonase-1 (PON-1) activity and low grade inflammation into account. METHODS:
      The HDL anti-inflammatory capacity, determined as the ability to suppress tumor
      necrosis factor-alpha (TNF-alpha) induced vascular cell adhesion molecule-1 (VCAM
      1) mRNA expression in endothelial cells in vitro (higher values indicate lower
      anti-inflammatory capacity), PON-1 (arylesterase) activity, hs-C-reactive protein
      (hs-CRP), serum amyloid A (SAA) and TNF-alpha were compared in 40 subjects with
      T2DM (no insulin or statin treatment) and 36 non-diabetic subjects. RESULTS: T2DM
      was associated with impaired HDL anti-inflammatory capacity (3.18 vs 1.05 fold
      increase in VCAM-1 mRNA expression; P < 0.001), coinciding with decreased HDL
      cholesterol (P = 0.001), apolipoprotein A-I (P = 0.038) and PON-1 activity (P =
      0.023), as well as increased hs-CRP (P = 0.043) and TNF-alpha (P = 0.005). In all
      subjects combined, age- and sex-adjusted multivariable linear regression analysis
      demonstrated that impaired HDL anti-inflammatory capacity was associated with
      hyperglycemia (beta = 0.499, P < 0.001), lower PON-1 activity (beta = - 0.192, P
      = 0.030) and higher hs-CRP (beta = 0.220, P = 0.016). CONCLUSIONS: The HDL anti
      inflammatory capacity is substantially impaired in T2DM, at least partly
      attributable to the degree of hyperglycemia, decreased PON-1 activity and
      enhanced low grade chronic inflammation. Decreased anti-inflammatory protection
      capacity of HDL conceivably contributes to the increased atherosclerosis risk
      associated with T2DM.

PMID- 29025407
TI  - Severe anemia due to pharyngeal leech infestation; a case report from Ethiopia.
AB  - BACKGROUND: Leeches are rare blood-sucking endoparasites. Swimming in streams and
      ponds as well as drinking contaminated water are the major ways to acquire
      leeches. CASE PRESENTATION: A 6 year old boy who came with a history of
      hematemesis, frequent spitting of blood stained saliva, fatigue and anorexia to a
      rural hospital in Ethiopia. This was a rare case of severe anemia caused by a
      single leech infestation of laryngopharynx that required blood transfusion.
      CONCLUSION: Leech infestation should be considered as a source of unexplained
      hematemesis, spitting of blood and severe anemia in rural areas.

PMID- 29025406
TI  - Impact of empagliflozin on subclinical left ventricular dysfunctions and on the
      mechanisms involved in myocardial disease progression in type 2 diabetes:
      rationale and design of the EMPA-HEART trial.
AB  - BACKGROUND: Asymptomatic left ventricular (LV) dysfunction is highly prevalent in
      type 2 diabetes patients. Unlike the other hypoglycemic drugs, SGLT2 inhibitors
      have shown potential benefits for reducing cardiovascular death and risk factors,
      aside from lowering plasma glucose levels. With this study we aim at determining
      whether the treatment with empagliflozin is associated with an improvement in LV
      functions in diabetic patients with asymptomatic LV dysfunction against
      Sitagliptin, which is presumably neutral on myocardial function. To determine
      changes in LV systolic and diastolic functions we will use speckle-tracking
      echocardiography, a novel sensitive, non-invasive, bedside method allowing the
      calculation of LV global longitudinal strain (GLS), an index of myocardial
      deformability, as well as 3D echocardiography, which allows a better evaluation
      of LV volumes and mass. METHODS: The EMPA-HEART trial will be a phase III, open
      label, active-controlled, parallel groups, single centre, exploratory study
      conducted in Pisa, Italy. A cohort of 75 diabetic patients with normal LV
      systolic (2D-Echo EF > 50%) and renal (eGFR sec MDRD > 60 ml/min/1.73 mq)
      functions and no evidence of valvular and/or ischemic heart disease will be
      randomized to either Empagliflozin 10 mg/die or Sitagliptin 100 mg/die. The
      primary outcome is to detect a change in GLS from baseline to 1 and 6 months
      after treatment initiation. The secondary outcomes include changes from baseline
      to 6 months in 3-D Echocardiography EF, left atrial volume and E/E', VO2max as
      measured at cardiopulmonary test, cardiac autonomic function tests (R-R interval
      during Valsalva manoeuvre, deep-breathing, lying-to-standing), and the
      determination of a set of plasma biomarkers aimed at studying volume,
      inflammation, oxidative stress, matrix remodelling, myocyte strain and injury.
      DISCUSSION: SGLT2 inhibitors might affect myocardial functions through mechanisms
      acting both directly and indirectly on the myocardium. The set of instrumental
      and biohumoral tests of our study might actually detect the presence and entity
      of empagliflozin beneficial effects on the myocardium and shed light on the
      mechanisms involved. Further, this study might eventually provide information to
      design a clinical strategy, based on echocardiography and/or biomarkers, to
      select the patients who might benefit more from this intervention. Trial
      registration EUDRACT Code 2016-0022250-10.

PMID- 29025408
TI  - Synteny analysis of genes and distribution of loci controlling oil content and
      fatty acid profile based on QTL alignment map in Brassica napus.
AB  - BACKGROUND: Deciphering the genetic architecture of a species is a good way to
      understand its evolutionary history, but also to tailor its profile for breeding
      elite cultivars with desirable traits. Aligning QTLs from diverse population in
      one map and utilizing it for comparison, but also as a basis for multiple
      analyses assure a stronger evidence to understand the genetic system related to a
      given phenotype. RESULTS: In this study, 439 genes involved in fatty acid (FA)
      and triacylglycerol (TAG) biosyntheses were identified in Brassica napus. B.
      napus genome showed mixed gene loss and insertion compared to B. rapa and B.
      oleracea, and C genome had more inserted genes. Identified QTLs for oil (OC-QTLs)
      and fatty acids (FA-QTLs) from nine reported populations were projected on the
      physical map of the reference genome "Darmor-bzh" to generate a map. Thus, 335 FA
      QTLs and OC-QTLs could be highlighted and 82 QTLs were overlapping. Chromosome C3
      contained 22 overlapping QTLs with all trait studied except for C18:3. In total,
      218 candidate genes which were potentially involved in FA and TAG were identified
      in 162 QTLs confidence intervals and some of them might affect many traits. Also,
      76 among these candidate genes were found inside 57 overlapping QTLs, and
      candidate genes for oil content were in majority (61/76 genes). Then, sixteen
      genes were found in overlapping QTLs involving three populations, and the
      remaining 60 genes were found in overlapping QTLs of two populations. Interaction
      network and pathway analysis of these candidate genes indicated ten genes that
      might have strong influence over the other genes that control fatty acids and oil
      formation. CONCLUSION: The present results provided new information for genetic
      basis of FA and TAG formation in B. napus. A map including QTLs from numerous
      populations was built, which could serve as reference to study the genome profile
      of B. napus, and new potential genes emerged which might affect seed oil. New
      useful tracks were showed for the selection of population or/and selection of
      interesting genes for breeding improvement purpose.

PMID- 29025409
TI  - Genes for asparagine metabolism in Lotus japonicus: differential expression and
      interconnection with photorespiration.
AB  - BACKGROUND: Asparagine is a very important nitrogen transport and storage
      compound in plants due to its high nitrogen/carbon ratio and stability.
      Asparagine intracellular concentration depends on a balance between asparagine
      biosynthesis and degradation. The main enzymes involved in asparagine metabolism
      are asparagine synthetase (ASN), asparaginase (NSE) and serine-glyoxylate
      aminotransferase (SGAT). The study of the genes encoding for these enzymes in the
      model legume Lotus japonicus is of particular interest since it has been proposed
      that asparagine is the principal molecule used to transport reduced nitrogen
      within the plant in most temperate legumes. RESULTS: A differential expression of
      genes encoding for several enzymes involved in asparagine metabolism was detected
      in L. japonicus. ASN is encoded by three genes, LjASN1 was the most highly
      expressed in mature leaves while LjASN2 expression was negligible and LjASN3
      showed a low expression in this organ, suggesting that LjASN1 is the main gene
      responsible for asparagine synthesis in mature leaves. In young leaves, LjASN3
      was the only ASN gene expressed although at low levels, while all the three genes
      encoding for NSE were highly expressed, especially LjNSE1. In nodules, LjASN2 and
      LjNSE2 were the most highly expressed genes, suggesting an important role for
      these genes in this organ. Several lines of evidence support the connection
      between asparagine metabolic genes and photorespiration in L. japonicus: a) a
      mutant plant deficient in LjNSE1 showed a dramatic decrease in the expression of
      the two genes encoding for SGAT; b) expression of the genes involved in
      asparagine metabolism is altered in a photorespiratory mutant lacking plastidic
      glutamine synthetase; c) a clustering analysis indicated a similar pattern of
      expression among several genes involved in photorespiratory and asparagine
      metabolism, indicating a clear link between LjASN1 and LjSGAT genes and
      photorespiration. CONCLUSIONS: The results obtained in this paper indicate the
      existence of a differential expression of asparagine metabolic genes in L.
      japonicus and point out the crucial relevance of particular genes in different
      organs. Moreover, the data presented establish clear links between asparagine and
      photorespiratory metabolic genes in this plant.

PMID- 29025410
TI  - Association between traditional cardiovascular risk factors and mortality in the
      oldest old: untangling the role of frailty.
AB  - BACKGROUND: To date, there is no consensus regarding cardiovascular risk
      management in the very old. Studies have shown that the relationship between
      traditional cardiovascular risk factors and mortality is null or even inverted
      within this age group. This relationship could be modified by the presence of
      frailty. This study was performed to examine the effect of frailty on the
      association between cardiovascular risk factors and mortality in the oldest old.
      METHODS: The BELFRAIL study is a prospective, observational, population-based
      cohort study of 567 subjects aged 80 years and older. Data on cardiovascular risk
      factors were recorded. Frailty was assessed using three different models: the
      Groningen Frailty Indicator, Fried and Puts models. Participants were considered
      robust if they were 'not frail' according to all three models, and frail if they
      met the frailty criteria for one of the three models. The follow-up data on
      mortality and cause of death were registered. RESULTS: No cardiovascular risk
      factor was associated with mortality in subjects with and without cardiovascular
      disease. The presence of frailty was a strong risk factor for mortality [HR: 2.5,
      95%CI: (1.9-3.2) for all-cause mortality; HR: 2.2, 95%CI: (1.4-3.4) for
      cardiovascular mortality]. In robust patients, a history of cardiovascular
      disease increased the risk for mortality [HR: 1.7, 95%CI: (1.1-2.5) for all-cause
      mortality; HR: 2.2, 95%CI: (1.2-3.9) for cardiovascular mortality]. In frail
      patients, there was no association between any of the traditional risk factors
      and mortality. CONCLUSIONS: Traditional cardiovascular risk factors were not
      associated with mortality in very old subjects. Frailty was shown to be a strong
      risk factor for mortality in this age group. However, frailty could not be used
      to identify additional subjects who might benefit more from cardiovascular risk
      management.

PMID- 29025411
TI  - Maize RNA PolIV affects the expression of genes with nearby TE insertions and has
      a genome-wide repressive impact on transcription.
AB  - BACKGROUND: RNA-directed DNA methylation (RdDM) is a plant-specific epigenetic
      process that relies on the RNA polymerase IV (Pol IV) for the production of 24
      nucleotide small interfering RNAs (siRNA) that guide the cytosine methylation and
      silencing of genes and transposons. Zea mays RPD1/RMR6 gene encodes the largest
      subunit of Pol IV and is required for normal plant development, paramutation,
      transcriptional repression of certain transposable elements (TEs) and
      transcriptional regulation of specific alleles. RESULTS: In this study we applied
      a total RNA-Seq approach to compare the B73 and rpd1/rmr6 leaf transcriptomes.
      Although previous studies indicated that loss of siRNAs production in RdDM
      mutants provokes a strong loss of CHH DNA methylation but not massive gene or TEs
      transcriptional activation in both Arabidopsis and maize, our total RNA-Seq
      analysis of rpd1/rmr6 transcriptome reveals that loss of Pol IV activity causes a
      global increase in the transcribed fraction of the maize genome. Our results
      point to the genes with nearby TE insertions as being the most strongly affected
      by Pol IV-mediated gene silencing. TEs modulation of nearby gene expression is
      linked to alternative methylation profiles on gene flanking regions, and these
      profiles are strictly dependent on specific characteristics of the TE member
      inserted. Although Pol IV is essential for the biogenesis of siRNAs, the genes
      with associated siRNA loci are less affected by the pol IV mutation. CONCLUSIONS:
      This deep and integrated analysis of gene expression, TEs distribution, smallRNA
      targeting and DNA methylation levels, reveals that loss of Pol IV activity
      globally affects genome regulation, pointing at TEs as modulator of nearby gene
      expression and indicating the existence of multiple level epigenetic silencing
      mechanisms. Our results also suggest a predominant role of the Pol IV-mediated
      RdDM pathway in genome dominance regulation, and subgenome stability and
      evolution in maize.

PMID- 29025413
TI  - Carbohydrate-active enzymes in Trichoderma harzianum: a bioinformatic analysis
      bioprospecting for key enzymes for the biofuels industry.
AB  - BACKGROUND: Trichoderma harzianum is used in biotechnology applications due to
      its ability to produce powerful enzymes for the conversion of lignocellulosic
      substrates into soluble sugars. Active enzymes involved in carbohydrate
      metabolism are defined as carbohydrate-active enzymes (CAZymes), and the most
      abundant family in the CAZy database is the glycoside hydrolases. The enzymes of
      this family play a fundamental role in the decomposition of plant biomass.
      RESULTS: In this study, the CAZymes of T. harzianum were identified and
      classified using bioinformatic approaches after which the expression profiles of
      all annotated CAZymes were assessed via RNA-Seq, and a phylogenetic analysis was
      performed. A total of 430 CAZymes (3.7% of the total proteins for this organism)
      were annotated in T. harzianum, including 259 glycoside hydrolases (GHs), 101
      glycosyl transferases (GTs), 6 polysaccharide lyases (PLs), 22 carbohydrate
      esterases (CEs), 42 auxiliary activities (AAs) and 46 carbohydrate-binding
      modules (CBMs). Among the identified T. harzianum CAZymes, 47% were predicted to
      harbor a signal peptide sequence and were therefore classified as secreted
      proteins. The GH families were the CAZyme class with the greatest number of
      expressed genes, including GH18 (23 genes), GH3 (17 genes), GH16 (16 genes), GH2
      (13 genes) and GH5 (12 genes). A phylogenetic analysis of the proteins in the
      AA9/GH61, CE5 and GH55 families showed high functional variation among the
      proteins. CONCLUSIONS: Identifying the main proteins used by T. harzianum for
      biomass degradation can ensure new advances in the biofuel production field.
      Herein, we annotated and characterized the expression levels of all of the
      CAZymes from T. harzianum, which may contribute to future studies focusing on the
      functional and structural characterization of the identified proteins.

PMID- 29025414
TI  - HIV infected men who have sex with men in Israel: knowledge, attitudes and sexual
      behavior.
AB  - BACKGROUND: HIV-infected (HIVI) men who have sex with men (MSM) may transmit HIV
      to their sero-discordant sex partner/s. This study assesses the knowledge,
      attitudes and sex-practices of Israeli HIVI-MSM. METHODS: This cross-sectional
      study compared HIVI-MSM to self-reported HIV-uninfected (HIVU) MSM by using
      anonymous questionnaires that were distributed in AIDS-treatment centers and gay
      related internet-sites in 2015. Unprotected anal intercourse (UAI) in the last 6
      months was the outcome variable. RESULTS: Of 300 HIVI-MSM and 1299 HIVU-MSM, UAI
      with sero-discordant/unknown-status partner/s was performed by 12.1% and 17.9%,
      respectively, p=0.02. UAI with sero-discordant/unknown-status among HIVI-MSM and
      HIVU-MSM was associated with the type of partnership: 37.7% vs. 52.4% for steady
      partner/s, 19.0% vs. 39.9% for sex-buddies and 23.5% vs. 24.0% for casual
      partner/s (p<0.001, p=0.01, p=0.6), respectively. On these occasions, HIVI-MSM
      were more likely to be receptive during UAI: 92.3%, 87.5% and 83.3% for steady
      partner/s, sex buddies and casual partner/s, respectively. In cases HIVI-MSM
      performed UAI, 31.3% expected their partner/s to share responsibility for condom
      use vs. 9.7% of HIVU-MSM. HIVI-MSM were involved in risky sexual-behaviors, such
      as substances-use, earlier sexual debut and sex for money. HIVI-MSM were more
      likely to disclose their HIV-status with their partner before sex and
      demonstrated better knowledge about HIV-transmission than HIVU-MSM. CONCLUSION:
      HIVI-MSM performed UAI with sero-discordant/unknown-status partner/s less
      frequently than HIVU-MSM. Their condom-use practices were associated with the
      type of partner, and were lower for casual vs. steady partners or sex-buddies.
      HIVI-MSM tended to use sero-adaptive strategies to reduce the potential risk of
      HIV-transmission to their sero-discordant/unknown-status partner/s.

PMID- 29025412
TI  - Dynamic transcriptome and DNA methylome analyses on longissimus dorsi to identify
      genes underlying intramuscular fat content in pigs.
AB  - BACKGROUND: The intramuscular fat content (IMF) refers to the amount of fat
      within muscles, including the sum of phospholipids mainly found in cell
      membranes, triglycerides and cholesterol, and is determined both by hyperplasia
      and hypertrophy of adipocyte during the development of pigs. The IMF content is
      an important economic trait that is genetically controlled by multiple genes. The
      Laiwu pig is an indigenous fatty pig breed distributed in North China,
      characterized by excessively higher level of IMF content (9%~12%), therefore, is
      suitable for the identification of genes controlling IMF variations. To identify
      genes underlying IMF deposition, we performed genome-wide transcriptome and
      methylome analyses on longissimus dorsi (LD) muscle in Laiwu pigs across four
      developmental stages. RESULTS: A total of 22,524 expressed genes were detected
      and 1158 differentially expressed genes (DEGs) were hierarchically clustered in
      the LD muscle over four developmental stages from 60 d to 400 d. These genes were
      significantly clustered into four temporal expression profiles, and genes
      participating in fat cell differentiation and lipid biosynthesis processes were
      identified. From 120 d to 240 d, the period with the maximum IMF deposition rate,
      the lipid biosynthesis related genes (FOSL1, FAM213B and G0S2), transcription
      factors (TFs) (EGR1, KLF5, SREBF2, TP53 and TWIST1) and enriched pathways
      (steroid biosynthesis and fatty acid biosynthesis) were revealed; and fat
      biosynthesis relevant genes showing differences in DNA methylation in gene body
      or intergenic region were detected, such as FASN, PVALB, ID2, SH3PXD2B and EGR1.
      CONCLUSIONS: This study provides a comprehensive landscape of transcriptome of
      the LD muscle in Laiwu pigs ranging from 60 to 400 days old, and methylome of the
      LD muscle in 120 d and 240 d Laiwu pigs. A set of candidate genes and TFs
      involved in fat biosynthesis process were identified, which were probably
      responsible for IMF deposition. The results from this study would provide a
      reference for the identification of genes controlling IMF variation, and for
      exploring molecular mechanisms underlying IMF deposition in pigs.

PMID- 29025415
TI  - Genetic evidence of multiple invasions and a small number of founders of Asian
      Palmyra palm (Borassus flabellifer) in Thailand.
AB  - BACKGROUND: Borassus flabellifer or Asian Palmyra palm is an important crop for
      local economies in the South and Southeast Asia for its fruit and palm sugar
      production. Archeological and historical evidence indicated the presence of this
      species in Southeast Asia dating back at least 1500 years. B. flabellifer is
      believed to be originated in Africa, spread to South Asia and introduced into
      Southeast Asia through commercial routes and dissemination of cultures, however,
      the nature of its invasion and settlement in Thailand is unclear. RESULTS: Here,
      we analyzed genetic data of 230 B. flabellifer accessions across Thailand using
      17 EST-SSR and 12 gSSR polymorphic markers. Clustering analysis revealed that the
      population consisted of two genetic clusters (STRUCTURE K = 2). Cluster I is
      found mainly in southern Thailand, while Cluster II is found mainly in the
      northeastern. Those found in the central are of an extensive mix between the two.
      These two clusters are in moderate differentiation (F ST = 0.066 and N M = 3.532)
      and have low genetic diversity (HO = 0.371 and 0.416; AR = 2.99 and 3.19, for the
      cluster I and II respectively). The minimum numbers of founders for each genetic
      group varies from 3 to 4 individuals, based on simulation using different allele
      frequency assumptions. These numbers coincide with that B. flabellifer is
      dioecious, and a number of seeds had to be simultaneously introduced for
      obtaining both male and female founders. CONCLUSIONS: From these data and
      geographical and historical evidence, we hypothesize that there were at least two
      different invasive events of B. flabellifer in Thailand. B. flabellifer was
      likely brought through the Straits of Malacca to be propagated in the southern
      Thailand as one of the invasive events before spreading to the central Thailand.
      The second event likely occurred in Khmer Empire, currently Cambodia, before
      spreading to the northeastern Thailand.

PMID- 29025416
TI  - Impact of renal function on the underlying pathophysiology of coronary plaque
      composition in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Both the progression of diabetic kidney disease and increased
      glycemic variability play important roles in the pathogenesis of coronary plaque
      formation via inflammatory pathways in patients with type 2 diabetes mellitus
      (T2DM). Therefore we evaluated the role of renal function in the contributory
      effects of blood glucose fluctuations and blood levels of inflammatory cytokine
      concentrations on the tissue characteristics of coronary plaques in patients with
      T2DM. METHODS: We prospectively enrolled 71 T2DM patients (mean age: 68 +/- 9,
      male 79%) with 153 coronary artery lesions. Patients were divided into 2 groups
      according to their estimated glomerular filtration rate (eGFR) levels: Group 1
      (>= 60 mL/min/1.73 m2, n = 40) and Group 2 (< 60 mL/min/1.73 m2, n = 31). All
      patients underwent continuous glucose monitoring (CGM) for 120 h and the mean
      amplitude of glycemic excursions (MAGE) was calculated. Serum tumor necrosis
      factor (TNF)-alpha was also measured. In addition, gray-scale coronary
      intravascular ultrasound (IVUS) and iMap-IVUS were performed in the coronary
      lesions with < 50% luminal reduction. RESULTS: In Group 1, MAGE correlated with
      percent lipidic volume (%LV) (r = 0.477, p = 0.002). In this group, stepwise
      multivariate linear regression analyses showed that only MAGE was independently
      associated with %LV (beta = 0.477, p = 0.002). In contrast, in Group 2, only
      serum TNF-alpha correlated with percent fibrotic volume (%FV) (r = - 0.471, p =
      0.007), %LV (r = 0.496, p = 0.005) and percent necrotic volume (%NV) (r = 0.426,
      p = 0.017). In this group, stepwise multivariate linear regression analyses
      showed that only serum TNF-alpha was independently associated with each tissue
      characteristic (%FV beta = - 0.471 and p = 0.007, %LV beta = 0.496 and p = 0.005,
      %NV: beta = 0.426 and p = 0.017). CONCLUSIONS: In T2DM patients, the tissue
      characteristics of coronary plaques were associated with MAGE in patients with
      eGFR >= 60 mL/min/1.73 m2 and with serum TNF-alpha in those with eGFR < 60
      mL/min/1.73 m2.

PMID- 29025417
TI  - Human rights and mental health in post-apartheid South Africa: lessons from
      health care professionals working with suicidal inmates in the prison system.
AB  - BACKGROUND: During the era of apartheid in South Africa, a number of mental
      health professionals were vocal about the need for socio-economic and political
      reform. They described the deleterious psychological and social impact of the
      oppressive and discriminatory Nationalist state policies. However, they remained
      optimistic that democracy would usher in positive changes. In this article, we
      consider how mental health professionals working in post-apartheid South Africa
      experience their work. METHODS: Our aim was to describe the experience of mental
      health professionals working in prisons who provide care to suicidal prisoners.
      Data were collected from in-depth semi-structured interviews and were analyzed
      using thematic content analysis. RESULTS: Findings draw attention to the
      challenges mental health professionals in post-apartheid South Africa face when
      attempting to provide psychological care in settings where resources are scarce
      and where the environment is anti-therapeutic. Findings highlight the significant
      gap between current policies, which protect prisoners' human rights, and every
      day practices within prisons. CONCLUSIONS: The findings imply that there is still
      an urgent need for activism in South Africa, particularly in the context of
      providing mental health care services in settings which are anti-therapeutic and
      inadequately resourced, such as prisons.

PMID- 29025418
TI  - Food purchase patterns: empirical identification and analysis of their
      association with diet quality, socio-economic factors, and attitudes.
AB  - BACKGROUND: Empirically derived food purchase patterns provide information about
      which combinations of foods were purchased from households. The objective of this
      study was to identify what kinds of patterns exist, which level of diet quality
      they represent and which factors are associated with the patterns. METHODS: The
      study made use of representative German consumption data in which approximately
      12 million food purchases from 13,125 households are recorded. In accordance with
      healthy diet criteria the food purchases were assigned to 18 food groups of the
      German Food Pyramid. Based on these groups a factor analysis with a principal
      component technique was applied to identify food patterns. For these patterns
      nutrient and energy densities were examined. Using regression analysis,
      associations between pattern scores and socio-economic as well as attitude
      variables, reflecting personal statements about healthy eating, were analyzed.
      RESULTS: In total, three food purchase patterns could be identified: a natural, a
      processed and a traditional one. The first one was characterized by a higher
      purchasing of natural foods, the second by an increased purchasing of processed
      foods and the third by a meat-oriented diet. In each pattern there were specific
      diet quality criteria that could be improved whereas others were in line with
      actual dietary guidelines. In addition to socio-demographic factors, attitudes
      were significantly associated with the purchase patterns. CONCLUSIONS: The
      findings of this study are interesting from a public health perspective, as it
      can be assumed that measures focusing on specific aspects of diet quality are
      more promising than general ones. However, it is a major challenge to identify
      the population groups with their specific needs of improvement. As the patterns
      were associated with both socio-economic and attitude variables these grouping
      criteria could be used to define target groups.

PMID- 29025419
TI  - Strong associations between national prevalence of various STIs suggests sexual
      network connectivity is a common underpinning risk factor.
AB  - BACKGROUND: If national peak Human Immunodeficiency Virus (HIV) prevalence is
      positively associated with the prevalence of other sexually transmitted
      infections (STIs) from before or early on in the HIV epidemics this would suggest
      common underlying drivers. METHODS: Pearson's correlations were calculated
      between the prevalence of seven STIs at a country-level: chlamydia, gonorrhoea,
      trichomoniasis, syphilis, bacterial vaginosis, herpes simplex virus-2 (HSV-2) and
      HIV. RESULTS: The prevalence of all the STIs was highest in the sub-Saharan
      African region excluding chlamydia. The prevalence of all seven STIs were
      positively correlated excluding chlamydia. The correlations were strongest for
      HIV-HSV-2 (r = 0.85, P < 0.0001) and HSV-2-trichomoniasis (r = 0.82, P < 0.0001).
      CONCLUSION: Our results of a generally positive association between the
      prevalences of a range of STIs suggests that higher prevalences were driven by
      common underlying determinants. We review different types of evidence which
      suggest that differential sexual connectivity is a plausible common determinant.

PMID- 29025421
TI  - Correction to: Optimization and validation of sample preparation for metagenomic
      sequencing of viruses in clinical samples.

PMID- 29025420
TI  - Genetic variation and population structure of maize inbred lines adapted to the
      mid-altitude sub-humid maize agro-ecology of Ethiopia using single nucleotide
      polymorphic (SNP) markers.
AB  - BACKGROUND: Molecular characterization is important for efficient utilization of
      germplasm and development of improved varieties. In the present study, we
      investigated the genetic purity, relatedness and population structure of 265
      maize inbred lines from the Ethiopian Institute of Agricultural Research (EIAR),
      the International Maize and Wheat Improvement Centre (CIMMYT) and the
      International Institute of Tropical Agriculture (IITA) using 220,878 single
      nucleotide polymorphic (SNP) markers obtained using genotyping by sequencing
      (GBS). RESULTS: Only 22% of the inbred lines were considered pure with <5%
      heterogeneity, while the remaining 78% of the inbred lines had a heterogeneity
      ranging from 5.1 to 31.5%. Pairwise genetic distances among the 265 inbred lines
      varied from 0.011 to 0.345, with 89% of the pairs falling between 0.301 and
      0.345. Only <1% of the pairs had a genetic distance lower than 0.200, which
      included 14 pairs of sister lines that were nearly identical. Relative kinship
      analysis showed that the kinship coefficients for 59% of the pairs of lines was
      close to zero, which agrees with the genetic distance estimates. Principal
      coordinate analysis, discriminant analysis of principal components (DAPC) and the
      model-based population structure analysis consistently suggested the presence of
      three groups, which generally agreed with pedigree information (genetic
      background). Although not distinct enough, the SNP markers showed some level of
      separation between the two CIMMYT heterotic groups A and B established based on
      pedigree and combining ability information. CONCLUSIONS: The high level of
      heterogeneity detected in most of the inbred lines suggested the requirement for
      purification or further inbreeding except those deliberately maintained at early
      inbreeding level. The genetic distance and relative kinship analysis clearly
      indicated the uniqueness of most of the inbred lines in the maize germplasm
      available for breeders in the mid-altitude maize breeding program of Ethiopia.
      Results from the present study facilitate the maize breeding work in Ethiopia and
      germplasm exchange among breeding programs in Africa. We suggest the
      incorporation of high density molecular marker information in future heterotic
      group assignments.

PMID- 29025422
TI  - Readout-segmented multi-shot diffusion-weighted MRI of the knee joint in patients
      with juvenile idiopathic arthritis.
AB  - BACKGROUND: Diffusion-weighted MRI has been proposed as a new technique for
      imaging synovitis without intravenous contrast application. We investigated
      diagnostic utility of multi-shot readout-segmented diffusion-weighted MRI (multi
      shot DWI) for synovial imaging of the knee joint in patients with juvenile
      idiopathic arthritis (JIA). METHODS: Thirty-two consecutive patients with
      confirmed or suspected JIA (21 girls, median age 13 years) underwent routine 1.5
      T MRI with contrast-enhanced T1w imaging (contrast-enhanced MRI) and with multi
      shot DWI (RESOLVE, b-values 0-50 and 800 s/mm2). Contrast-enhanced MRI,
      representing the diagnostic standard, and diffusion-weighted images at b = 800
      s/mm2 were separately rated by three independent blinded readers at different
      levels of expertise for the presence and the degree of synovitis on a modified 5
      item Likert scale along with the level of subjective diagnostic confidence.
      RESULTS: Fourteen (44%) patients had active synovitis and joint effusion, nine
      (28%) patients showed mild synovial enhancement not qualifying for arthritis and
      another nine (28%) patients had no synovial signal alterations on contrast
      enhanced imaging. Ratings by the 1st reader on contrast-enhanced MRI and on DWI
      showed substantial agreement (kappa = 0.74). Inter-observer-agreement was high
      for diagnosing, or ruling out, active arthritis of the knee joint on contrast
      enhanced MRI and on DWI, showing full agreement between 1st and 2nd reader and
      disagreement in one case (3%) between 1st and 3rd reader. In contrast, ratings in
      cases of absent vs. little synovial inflammation were markedly inconsistent on
      DWI. Diagnostic confidence was lower on DWI, compared to contrast-enhanced
      imaging. CONCLUSION: Multi-shot DWI of the knee joint is feasible in routine
      imaging and reliably diagnoses, or rules out, active arthritis of the knee joint
      in paediatric patients without the need of gadolinium-based i.v. contrast
      injection. Possibly due to "T2w shine-through" artifacts, DWI does not reliably
      differentiate non-inflamed joints from knee joints with mild synovial irritation.

PMID- 29025424
TI  - Understanding immune phenotypes in human gastric disease tissues by multiplexed
      immunohistochemistry.
AB  - BACKGROUND: Understanding immune phenotypes and human gastric disease in situ
      requires an approach that leverages multiplexed immunohistochemistry (mIHC) with
      multispectral imaging to facilitate precise image analyses. METHODS: We developed
      a novel 4-color mIHC assay based on tyramide signal amplification that allowed us
      to reliably interrogate immunologic checkpoints, including programmed death
      ligand 1 (PD-L1), cytotoxic T cells (CD8+T) and regulatory T cells (Foxp3), in
      formalin-fixed, paraffin-embedded tissues of various human gastric diseases. By
      observing cell phenotypes within the disease tissue microenvironment, we were
      able to determine specific co-localized staining combinations and various
      measures of cell density. RESULTS: We found that PD-L1 was expressed in gastric
      ulcer and in tumor cells (TCs), as well as in tumor-infiltrating immune cells
      (TIICs), but not in normal gastric mucosa or other gastric intraepithelial
      neoplastic tissues. Furthermore, we found no significant reduction in CD8+T
      cells, whereas the ratio of CD8+T:Foxp3 cells and CD8+T:PD-L1 cells was
      suppressed in tumor tissues and elevated in adjacent normal tissues. An
      unsupervised hierarchical analysis also identified correlations between CD8+T and
      Foxp3+ tumor-infiltrating lymphocyte (TIL) densities and average PD-L1 levels.
      Three main groups were identified based on the results of CD8+T:PD-L1 ratios in
      gastric tumor tissues. Furthermore, integrating CD8+T:Foxp3 ratios, which
      increased the complexity for immune phenotype status, revealed 6-7 clusters that
      enabled the separation of gastric cancer patients at the same clinical stage into
      different risk-group subsets. CONCLUSIONS: Characterizing immune phenotypes in
      human gastric disease tissues via multiplexed immunohistochemistry may help guide
      PD-L1 clinical therapy. Observing unique disease tissue microenvironments can
      improve our understanding of immune phenotypes and cell interactions within these
      microenvironments, providing the ability to predict safe responses to
      immunotherapies.

PMID- 29025423
TI  - Downregulation of NMI promotes tumor growth and predicts poor prognosis in human
      lung adenocarcinomas.
AB  - BACKGROUND: N-myc (and STAT) interactor (NMI) plays vital roles in tumor growth,
      progression, and metastasis. In this study, we identified NMI as a potential
      tumor suppressor in lung cancer and explored its molecular mechanism involved in
      lung cancer progression. METHODS: Human lung cancer cell lines and a mouse
      xenograft model was used to study the effect of NMI on tumor growth. The
      expression of NMI, COX-2 and relevant signaling proteins were examined by Western
      blot. Tissue microarray immunohistochemical analysis was performed to assess the
      correlation between NMI and COX-2 expression in lung cancer patients. RESULTS:
      NMI was highly expressed in normal lung cells and tissues, but lowly expressed in
      lung cancer cells and tissues. Overexpression of NMI induced apoptosis,
      suppressed lung cancer cell growth and migration, which were mediated by up
      regulation of the cleaved caspase-3/9 and down-regulation of phosphorylated
      PI3K/AKT, MMP2/MMP9, beta-cadherin, and COX-2/PGE2. In contrast, knockdown of NMI
      promoted lung cancer cell colony formation and migration, which were correlated
      with the increased expression of phosphorylated PI3K/AKT, MMP2/MMP9, beta
      cadherin and COX-2/PGE2. Further study showed that NMI suppressed COX-2
      expression through inhibition of the p50/p65 NF-kappaB acetylation mediated by
      p300. The xenograft lung cancer mouse models also confirmed the NMI-mediated
      suppression of tumor growth by inhibiting COX-2 signaling. Moreover, tissue
      microarray immunohistochemical analysis of lung adenocarcinomas also demonstrated
      a negative correlation between NMI and COX-2 expression. Kaplan-Meier analysis
      indicated that the patients with high level of NMI had a significantly better
      prognosis. CONCLUSIONS: Our study showed that NMI suppressed tumor growth by
      inhibiting PI3K/AKT, MMP2/MMP9, COX-2/PGE2 signaling pathways and p300-mediated
      NF-kappaB acetylation, and predicted a favorable prognosis in human lung
      adenocarcinomas, suggesting that NMI was a potential tumor suppressor in lung
      cancer.

PMID- 29025425
TI  - Prognostic utility of differential tissue characterization of cardiac neoplasm
      and thrombus via late gadolinium enhancement cardiovascular magnetic resonance
      among patients with advanced systemic cancer.
AB  - BACKGROUND: Late gadolinium enhancement (LGE-) cardiovascular magnetic resonance
      (CMR) is well-validated for cardiac mass (CMASS) tissue characterization to
      differentiate neoplasm (CNEO) from thrombus (CTHR): Prognostic implications of
      CMASS subtypes among systemic cancer patients are unknown. METHODS: CMASS +
      patients and controls (CMASS -) matched for cancer diagnosis and stage underwent
      a standardized CMR protocol, including LGE-CMR (IR-GRE) for tissue
      characterization and balanced steady state free precession cine-CMR (SSFP) for
      cardiac structure/function. CMASS subtypes (CNEO, CTHR) were respectively defined
      by presence or absence of enhancement on LGE-CMR; lesions were quantified for
      tissue properties (contrast-to-noise ratio (CNR); signal-to-noise ratio (SNR) and
      size. Clinical follow-up was performed to evaluate prognosis in relation to CMASS
      etiology. RESULTS: The study population comprised 126 patients with systemic
      neoplasms referred for CMR, of whom 50% (n = 63) had CMASS + (CNEO = 32%, CTHR =
      18%). Cancer etiology differed between CNEO (sarcoma = 20%, lung = 18%) and CTHR
      (lymphoma = 30%, GI = 26%); cardiac function (left ventricular ejection fraction:
      63 +/- 9 vs. 62 +/- 10%; p = 0.51? right ventricular ejection fraction: 53 +/- 9
      vs. 54 +/- 8%; p = 0.47) and geometric indices were similar (all p = NS). LGE-CMR
      tissue properties assessed by CNR (13.1 +/- 13.0 vs. 1.6 +/- 1.0; p < 0.001) and
      SNR (29.7 +/- 20.4 vs. 15.0 +/- 11.4, p = 0.003) were higher for CNEO, consistent
      with visually-assigned diagnostic categories. CTHR were more likely to localize
      to the right atrium (78% vs. 25%, p < 0.001); nearly all (17/18) were associated
      with central catheters. Lesion size (17.3 +/- 23.8 vs. 2.0 +/- 1.5 cm2; p <
      0.001) was greater with CNEO vs. CTHR, as was systemic disease burden (cancer
      involved organs: 3.6 +/- 2.0 vs. 2.3 +/- 2.1; p = 0.02). Mortality during a
      median follow-up of 2.5 years was markedly higher among patients with CNEO
      compared to those with CTHR (HR = 3.13 [CI 1.54-6.39], p = 0.002); prognosis was
      similar when patients were stratified by lesion size assessed via area (HR = 0.99
      per cm2 [CI 0.98-1.01], p = 0.40) or maximal diameter (HR = 0.98 per cm [CI 0.91
      1.06], p = 0.61). CTHR conferred similar mortality risk compared to cancer
      matched controls without cardiac involvement (p = 0.64) whereas mortality
      associated with CNEO was slightly higher albeit non-significant (p = 0.12).
      CONCLUSIONS: Among a broad cancer cohort with cardiac masses, CNEO defined by LGE
      CMR tissue characterization conferred markedly poorer prognosis than CTHR,
      whereas anatomic assessment via cine-CMR did not stratify mortality risk. Both
      CNEO and CTHR are associated with similar prognosis compared to CMASS - controls
      matched for cancer type and disease extent.

PMID- 29025427
TI  - Adaptive hybrid robotic system for rehabilitation of reaching movement after a
      brain injury: a usability study.
AB  - BACKGROUND: Brain injury survivors often present upper-limb motor impairment
      affecting the execution of functional activities such as reaching. A currently
      active research line seeking to maximize upper-limb motor recovery after a brain
      injury, deals with the combined use of functional electrical stimulation (FES)
      and mechanical supporting devices, in what has been previously termed hybrid
      robotic systems. This study evaluates from the technical and clinical
      perspectives the usability of an integrated hybrid robotic system for the
      rehabilitation of upper-limb reaching movements after a brain lesion affecting
      the motor function. METHODS: The presented system is comprised of four main
      components. The hybrid assistance is given by a passive exoskeleton to support
      the arm weight against gravity and a functional electrical stimulation device to
      assist the execution of the reaching task. The feedback error learning (FEL)
      controller was implemented to adjust the intensity of the electrical stimuli
      delivered on target muscles according to the performance of the users. This
      control strategy is based on a proportional-integral-derivative feedback
      controller and an artificial neural network as the feedforward controller. Two
      experiments were carried out in this evaluation. First, the technical viability
      and the performance of the implemented FEL controller was evaluated in healthy
      subjects (N = 12). Second, a small cohort of patients with a brain injury (N = 4)
      participated in two experimental session to evaluate the system performance.
      Also, the overall satisfaction and emotional response of the users after they
      used the system was assessed. RESULTS: In the experiment with healthy subjects, a
      significant reduction of the tracking error was found during the execution of
      reaching movements. In the experiment with patients, a decreasing trend of the
      error trajectory was found together with an increasing trend in the task
      performance as the movement was repeated. Brain injury patients expressed a great
      acceptance in using the system as a rehabilitation tool. CONCLUSIONS: The study
      demonstrates the technical feasibility of using the hybrid robotic system for
      reaching rehabilitation. Patients' reports on the received intervention reveal a
      great satisfaction and acceptance of the hybrid robotic system. TRIAL
      REGISTRATION: Retrospective trial registration in ISRCTN Register with study ID
      ISRCTN12843006 .

PMID- 29025428
TI  - Compound heterozygosity for two GHR missense mutations in a patient affected by
      Laron Syndrome: a case report.
AB  - BACKGROUND: Mutations localized in the Growth Hormone Receptor (GHR) gene are
      often associated with the pathogenesis of Laron Syndrome, an autosomal recessive
      hereditary disorder characterized by severe growth retardation. Biochemically,
      patients present normal to high circulating GH levels, in presence of very low or
      undetectable IGF-I levels, which do not rise after rhGH treatment. CASE
      PRESENTATION: We describe the case of a 3.8 years old girl with symmetrical short
      stature (-3.76 SDS), low IGF-1 and IGFBP-3, in presence of normal GH levels.
      Parents were not relatives and there was no family history of short stature.
      During the second day of birth, she developed severe hypoglycaemia that required
      glucose infusion. She presented frontal bossing and depressed nasal bridge. IGF-1
      generation test showed no response, suggesting a GH resistance evidence. In the
      hypothesis of Laron Syndrome, we decided to perform a molecular analysis of
      Growth Hormone Receptor (GHR) gene. This analysis demonstrated that the patient
      was compound heterozygote for two missense mutations. CONCLUSIONS: GHR gene
      mutations are a well demonstrated cause of GH insensitivity. In heterozygous
      patients, probably the normal stature may be achieved by a compensatory mechanism
      of GH secretion or signalling. On the contrary, in homozygous or compound
      heterozygous patients these compensatory mechanisms are inadequate, and short
      stature may be the consequence.

PMID- 29025429
TI  - Updated clinical guidelines experience major reporting limitations.
AB  - BACKGROUND: The Checklist for the Reporting of Updated Guidelines (CheckUp) was
      recently developed. However, so far, no systematic assessment of the reporting of
      updated clinical guidelines (CGs) exists. We aimed to examine (1) the
      completeness of reporting the updating process in CGs and (2) the inter-observer
      reliability of CheckUp. METHODS: We conducted a systematic assessment of the
      reporting of the updating process in a sample of updated CGs using CheckUp. We
      performed a systematic search to identify updated CGs published in 2015,
      developed by a professional society, reporting a systematic review of the
      evidence, and containing at least one recommendation. Three reviewers
      independently assessed the CGs with CheckUp (16 items). We calculated the median
      score per item, per domain, and overall, converting scores to a 10-point scale.
      Multiple linear regression analyses were used to identify differences according
      to country, type of organisation, scope, and health topic of updated CGs. We
      calculated the intraclass coefficient (ICC) and 95% confidence interval (95% CI)
      for domains and overall score. RESULTS: We included in total 60 updated CGs. The
      median domain score on a 10-point scale for presentation was 5.8 (range 1.7 to
      10), for editorial independence 8.3 (range 3.3 to 10), and for methodology 5.7
      (range 0 to 10). The median overall score on a 10-point scale was 6.3 (range 3.1
      to 10). Presentation and justification items at recommendation level
      (respectively reported by 27 and 38% of the CGs) and the methods used for the
      external review and implementing changes in practice were particularly poorly
      reported (both reported by 38% of the CGs). CGs developed by a European or
      international institution obtained a statistically significant higher overall
      score compared to North American or Asian institutions (p = 0.014). Finally, the
      agreement among the reviewers on the overall score was excellent (ICC 0.88, 95%
      CI 0.75 to 0.95). CONCLUSIONS: The reporting of updated CGs varies considerably
      with significant room for improvement. We recommend using CheckUp to assess the
      updating process in updated CGs and as a blueprint to inform methods and
      reporting strategies in updating.

PMID- 29025430
TI  - Genetic architecture of lipid traits in the Hispanic community health study/study
      of Latinos.
AB  - BACKGROUND: Despite ethnic disparities in lipid profiles, there are few genome
      wide association studies investigating genetic variation of lipids in non
      European ancestry populations. In this study, we present findings from genetic
      association analyses for total cholesterol, low density lipoprotein cholesterol
      (LDL), high density lipoprotein cholesterol (HDL), and triglycerides in a large
      Hispanic/Latino cohort in the U.S., the Hispanic Community Health Study / Study
      of Latinos (HCHS/SOL). METHODS: We estimated a heritability of approximately 20%
      for each lipid trait, similar to previous estimates in Europeans. To search for
      novel lipid loci, we performed conditional association analysis in which the
      statistical model was adjusted for previously reported SNPs associated with any
      of the four lipid traits. SNPs that remained genome-wide significant (P < 5 * 10
      8) after conditioning on known loci were evaluated for replication. RESULTS: We
      identified eight potentially novel lipid signals with minor allele frequencies
      <1%, none of which replicated. We tested previously reported SNP-trait
      associations for generalization to Hispanics/Latinos via a statistical framework.
      The generalization analysis revealed that approximately 50% of previously
      established lipid variants generalize to HCHS/SOL based on directional FDR r
      value < 0.05. Some failures to generalize were due to lack of power. CONCLUSIONS:
      These results demonstrate that many loci associated with lipid levels are shared
      across populations.

PMID- 29025432
TI  - Psychometric properties of the Diabetes Self-Management Questionnaire (DSMQ) in
      Urdu.
AB  - BACKGROUND: Numerous study tools on diabetes self-care have been introduced;
      however, most existing tools do not show expectable and meaningful correlations
      with patients' glycaemic control. The Diabetes Self-Management Questionnaire
      (DSMQ) was designed to appraise self-care activities which can predict glycaemic
      control outcomes. However, this tool has not been validated in Pakistan.
      Therefore, the aim of this study was to translate and examine the psychometric
      properties of the Urdu version of DSMQ among type 2 diabetes patients. METHOD:
      Standard forward-backward translation was used to translate the DSMQ into Urdu
      language. A convenience sample of 130 patients with type 2 diabetes was collected
      to assess the Urdu version's psychometric properties. Reliability was assessed by
      Cronbach's coefficient alpha and validity was assessed using confirmatory factor
      analysis and criterion-related correlations. RESULTS: High internal consistency
      was found for all DSMQ scales (Sum scale: alpha = 0.96, Glucose Management: 0.91;
      Dietary Control: 0.88; Physical Activity: 0.89; Health-Care Use: 0.73). The DSMQ
      subscales showed significant correlations with HbA1c (Glucose Management: -0.75;
      Dietary Control: -0.76; Physical Activity: -0.71; Health-Care Use: -0.64; Sum
      Scale: -0.78; all p < 0.001). However, when associations with HbA1c were assessed
      in one multiple linear regression model, only Glucose Management and Dietary
      Control were significantly associated with lower HbA1c values (Beta = -0.42, p =
      0.004 and Beta = -0.30, p = 0.028, respectively), while Physical Activity and
      Health-Care Use were not (p > 0.05). Adequate fit to the data was achieved for
      single factor model after successively modelling all significant correlations
      between the items' error terms, with Chi2 = 106.6, df = 84, p = 0.049; TLI =
      0.98, CFI = 0.99 and RMSEA = 0.05 (90% CI 0.01-0.07). Whereas a comparatively
      lower fit indices to data were observed in case of four factor model. CONCLUSION:
      The findings support the Urdu version of the DSMQ as a reliable and valid
      instrument for assessing self-care activities associated with glycaemic control
      in type 2 diabetes patients.

PMID- 29025431
TI  - Specific IgE and skin prick tests to diagnose allergy to fresh and baked cow's
      milk according to age: a systematic review.
AB  - BACKGROUND: The diagnosis of IgE-mediated cow's milk allergy is often based on
      anamnesis, and on specific IgE (sIgE) levels and/or Skin Prick Tests (SPT), which
      have both a good sensitivity but a low specificity, often causing positive
      results in non-allergic subjects. Thus, oral food challenge is still the gold
      standard test for diagnosis, though being expensive, time-consuming and possibly
      at risk for severe allergic reactions. AIM: The aim of the present study was to
      perform a systematic review of the studies that have so far analyzed the positive
      predictive values for sIgE and SPT in the diagnosis of allergy to fresh and baked
      cow's milk according to age, and to identify possible cut-offs that may be useful
      in clinical practice. METHODS: A comprehensive search on Medline via PubMed and
      Scopus was performed August 2017. Studies were included if they investigated
      possible sIgE and/or SPT cut-off values for cow's milk allergy diagnosis in
      pediatric patients. The quality of the studies was evaluated according to QUADAS
      2 criteria. RESULTS: The search produced 471 results on Scopus, and 2233 on
      PubMed. Thirty-one papers were included in the review and grouped according to
      patients' age, allergen type and cooking degree of the milk used for the oral
      food challenge. In children < 2 years, CMA diagnosis seems to be highly likely
      when sIgE to CM extract are >= 5 KUA/L or when SPT with commercial extract are
      above 6 mm or Prick by Prick (PbP) with fresh cow's milk are above 8 mm. Any cut
      offs are proposed for single cow's milk proteins and for baked milk allergy in
      children younger than 2 years. In Children >= 2 years of age it is hard to define
      practical cut-offs for allergy to fresh and baked cow's milk. Cut-offs identified
      are heterogeneous. CONCLUSIONS: None of the cut-offs proposed in the literature
      can be used to definitely confirm cow's milk allergy diagnosis, either to fresh
      pasteurized or to baked milk. However, in children < 2 years, cut-offs for
      specific IgE or SPT seem to be more homogeneous and may be proposed.

PMID- 29025433
TI  - The role of the glycosyl moiety of myricetin derivatives in anti-HIV-1 activity
      in vitro.
AB  - BACKGROUND: Plant extracts are sources of valuable compounds with biological
      activity, especially for the anti-proliferative activity against pathogens or
      tumor cells. Myricetin is a flavonoid found in several plants that has been
      described as an inhibitor of Human immunodeficiency virus type 1 (HIV-1) through
      its action against the HIV reverse transcriptase, but myricetin derivatives have
      not been fully studied. The aim of this study was to evaluate the anti-HIV-1
      activity of glycosylated metabolites obtained from Marcetia taxifolia and derived
      from myricetin: myricetin rhamnoside and myricetin 3-(6-rhamnosylgalactoside).
      METHODS: Compounds were obtained from organic extracts by maceration of aerial
      parts of M. taxifolia. All biological assays were performed in the MT4 cell line.
      Antiviral activity was measured as inhibition of p24 and reverse transcriptase
      with a fluorescent assay. RESULTS: Both flavonoids have antiviral activity in
      vitro, with an EC50 of 120 uM for myricetin 3-rhamnoside (MR) and 45 uM for
      myricetin 3-(6-rhamnosylgalactoside) (MRG), both significantly lower than the
      EC50 of myricetin (230 uM). Although both compounds inhibited the reverse
      transcriptase activity, with an IC50 of 10.6 uM for MR and 13.8 uM for MRG,
      myricetin was the most potent, with an IC50 of 7.6 uM, and an inhibition greater
      than 80%. Molecular docking approach showed correlation between the free energy
      of binding with the assays of enzyme inhibition. CONCLUSIONS: The results suggest
      that glycosylated moiety might enhance the anti-HIV-1 activity of myricetin,
      probably by favoring the internalization of the flavonoid into the cell. The
      inhibition of the HIV-1 reverse transcriptase is likely responsible for the
      antiviral activity.

PMID- 29025434
TI  - Minimum dietary diversity and associated factors among children aged 6-23 months
      in Addis Ababa, Ethiopia.
AB  - BACKGROUND: Dietary diversity has long been recognized as a key element of high
      quality diets. Minimum Dietary Diversity (MDD) is the consumption of four or more
      food groups from the seven food groups. Globally, only few children are receiving
      nutritionally adequate and diversified foods. More than two-thirds of
      malnutrition related child deaths are associated with inappropriate feeding
      practice during the first two years of life. In Ethiopia, only 7 % of children
      age 6-23 months had received the minimum acceptable diet. Therefore, the main aim
      of this study was to determine the level of minimum dietary diversity practice
      and identify the associated factors among children aged 6-23 months in Addis
      Ababa, Ethiopia. METHODS: A health facility based cross sectional study was
      undertaken in the three sub-cities of Addis Ababa from 26th February to 28th
      April, 2016. A multi-stage sampling technique was used to sample the 352 study
      participants or mothers who had children aged 6-23 months. Data were collected by
      using a structured and pretested questionnaire, cleaned and entered into Epi info
      7 and analyzed using SPSS 24 software. Logistic regression was fitted and odds
      ratio with 95% confidence interval (CI) with p-value less than 0.05 was used to
      identify factors associated with minimum dietary diversity. RESULT: In this
      study, the overall children with minimum dietary diversity score were found to be
      59.9%. Mother's educational attainment and a higher household monthly income were
      positively associated with the minimum dietary diversity practice. Similarly,
      mothers' knowledge on dietary diversity and child feeding was positively
      associated with minimum dietary diversity child feeding practice, with an
      adjusted odds ratio of 1.98 (95% CI: 1.11-3.53). CONCLUSION: In this study, the
      consumption of minimum dietary diversity was found to be high. In spite of this,
      more efforts need to be done to achieve the recommended minimum dietary diversity
      intake for all children aged between 6 and 23 months.

PMID- 29025437
TI  - Pieter van Musschenbroek on laws of nature.
AB  - In this article, we discuss the development of the concept of a 'law' (of nature)
      in the work of the Dutch natural philosopher and experimenter Petrus van
      Musschenbroek (1692-1761). Since Van Musschenbroek is commonly described as one
      of the first 'Newtonians' on the Continent in the secondary literature, we focus
      more specifically on its relation to Newton's views on this issue. Although he
      was certainly indebted to Newton for his thinking on laws (of nature), Van
      Musschenbroek's views can be seen to diverge from Newton's on crucial points. We
      show, moreover, how his thinking on laws of nature was shaped by both
      international and local factors. We start with a brief discussion of Newton's
      concept of 'laws of nature' in order to set the stage for Van Musschenbroek's. We
      then document the development of Van Musschenbroek's views on laws of nature in
      chronological order. We demonstrate how his thinking on laws of nature was tied
      to institutional, theological and scientific factors. We conclude by pointing to
      the broader significance of this case study for our understanding of the
      development of the concept 'law of nature' during the eighteenth century.

PMID- 29025436
TI  - Self-monitoring by Environmental Services May Not Accurately Measure Thoroughness
      of Hospital Room Cleaning.

PMID- 29025438
TI  - Pre-gestational excessive weight and duration of breast-feeding.
AB  - OBJECTIVE: To investigate whether pre-gestational obesity interferes with the
      duration of breast-feeding. DESIGN: A cross-sectional study was carried out with
      a population-based probabilistic sample. The dependent variables were exclusive
      breast-feeding (EBF) and breast-feeding (BF), as defined by the WHO. The
      classification of pre-gestational nutritional status was based on the pre
      gestational BMI category. SUBJECTS: A sample of 418 mother-infant pairs from the
      state of Alagoas, Brazil. RESULTS: The median duration of EBF was 1.9 months
      (60d), while that of BF was 8.2 months (250d). According to multiple linear
      regression analysis, the factors that negatively and independently affected the
      duration of EBF were pre-gestational BMI>=30.0 kg/m2 (-51.9d, 95 % CI -80.4, 
      23.4), maternal schooling<=9 years (-30.8d, 95 % CI -54.7, -6.9), no prior
      lactation experience (-29.0d, 95 % CI -45.6, -11.5) and infant pacifier use (
      41.4d; 95 % CI 54.5, -28.2). For BF, a higher weaning rate was observed during
      the first days after birth among children of pre-gestational obese mothers.
      CONCLUSIONS: The results suggest that higher pre-gestational BMI is associated
      with shorter duration of EBF and BF. Prenatal care provides a privileged
      opportunity to promote nutritional education, better nutritional status of
      pregnant woman, and greater success with EBF up to 6 months of age and with
      longer BF.

PMID- 29025435
TI  - Withania somnifera as a potential candidate to ameliorate high fat diet-induced
      anxiety and neuroinflammation.
AB  - BACKGROUND: The epidemic of obesity has reached alarming levels in both
      developing and developed nations. Excessive calorie intake and sedentary
      lifestyle due to technological advancements are the main causal factors for
      overweight and obesity among the human population. Obesity has been associated
      with a number of co-morbidities such as hypertension, type 2 diabetes mellitus,
      cardiovascular diseases, and neurodegeneration and dementia. The progression of
      neurological disorders in obese subjects has been mainly attributed to
      neuroinflammation. Withania somnifera has been used in numerous Ayurvedic
      formulations owing to its wide array of health-promoting properties. The current
      study was designed to test the hypothesis whether dry leaf powder of W. somnifera
      has anxiolytic and anti-neuroinflammatory potential in diet-induced obesity.
      METHODS: Young adult female rats were divided into four groups: low fat diet
      group (LFD) fed with regular chow feed, high fat diet group (HFD) fed with diet
      containing 30% fat by weight, low fat diet plus extract group (LFDE) fed with
      regular chow feed supplemented with dry leaf powder of W. somnifera 1 mg/g of
      body weight (ASH), and high fat diet plus extract group (HFDE) fed with diet
      containing 30% fat by weight and supplemented with ASH. All the animals were kept
      on respective feeding regimen for 12 weeks; following which, the animals were
      tested for their anxiety-like behavior using elevated plus maze test. The animals
      were sacrificed and used to study various inflammatory markers such as GFAP,
      Iba1, PPARgamma, iNOS, MCP-1, TNFalpha, IL-1beta, IL-6, and various markers of NF
      kappaB pathway by Western blotting and quantitative real-time PCR. Serum levels
      of leptin, insulin and pro-inflammatory cytokines were also assayed. RESULTS: ASH
      treated rats showed less anxiety levels as compared to HFD animals. At molecular
      level, ASH ameliorated the HFD-induced reactive gliosis and microgliosis and
      suppressed the expression of inflammatory markers such as PPARgamma, iNOS, MCP-1,
      TNFalpha, IL-1beta, and IL-6. Further, ASH ameliorated leptin and insulin
      resistance and prevented HFD-induced apoptosis. CONCLUSIONS: Dry leaf powder of
      W. somnifera may prove to be a potential therapeutic agent to attenuate
      neuroinflammation associated with obesity and may prevent its co-morbidities.

PMID- 29025439
TI  - End-of-life care and organ donation in South Africa - it's time for national
      policy to lead the way.

PMID- 29025440
TI  - Standardised training is the key to accuracy in triage.

PMID- 29025441
TI  - Need for advocacy for maternal immunisation.

PMID- 29025426
TI  - The complete European guidelines on phenylketonuria: diagnosis and treatment.
AB  - Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine
      metabolism caused by deficiency in the enzyme phenylalanine hydroxylase that
      converts phenylalanine into tyrosine. If left untreated, PKU results in increased
      phenylalanine concentrations in blood and brain, which cause severe intellectual
      disability, epilepsy and behavioural problems. PKU management differs widely
      across Europe and therefore these guidelines have been developed aiming to
      optimize and standardize PKU care. Professionals from 10 different European
      countries developed the guidelines according to the AGREE (Appraisal of
      Guidelines for Research and Evaluation) method. Literature search, critical
      appraisal and evidence grading were conducted according to the SIGN (Scottish
      Intercollegiate Guidelines Network) method. The Delphi-method was used when there
      was no or little evidence available. External consultants reviewed the
      guidelines. Using these methods 70 statements were formulated based on the
      highest quality evidence available. The level of evidence of most recommendations
      is C or D. Although study designs and patient numbers are sub-optimal, many
      statements are convincing, important and relevant. In addition, knowledge gaps
      are identified which require further research in order to direct better care for
      the future.

PMID- 29025442
TI  - The evolution of research participant protections in South Africa.
AB  - South Africa (SA) has played a leading role in health research internationally.
      Ethical guidelines for the protection of research participants have been
      published by the Medical Research Council (MRC) as early as 1979. Ironically, the
      guidelines gave substantial prominence to the oppressive laws of the time. In its
      4th edition of the guidelines, the MRC placed emphasis on SA needs, and
      incorporated the principles of the Bill of Rights of the SA Constitution 1996
      into its guidelines. The most significant milestone in the history of participant
      protections in SA was the inclusion of research and experimentation in the Bill
      of Rights of the Constitution and the statutory legislation of protections in the
      National Health Act No. 61 of 2003.

PMID- 29025443
TI  - Perceptions of nurses' roles in end-of-life care and organ donation - imposition
      or obligation?
AB  - South Africa has a rich organ-transplant history, and studies suggest that the SA
      public supports organ donation. In spite of this, persistently low donor numbers
      are a significant challenge. This may be due to a lack of contextually
      appropriate awareness and education, or to barriers to referring patients and
      families in clinical settings. It may also be due to ad hoc regulations that are
      not uniformly endorsed or implemented. In this article we present the findings of
      a study in Johannesburg that explored the attitudes and roles of nurses in end-of
      life care and organ donation. A total of 273 nurses participated. Most were
      female and <50 years old. The majority expressed positive attitudes towards both
      end-of-life care and organ donation, but there was ambiguity as to whether
      referring patients and families for these services was within nursing scope of
      practice. The vast majority of participants noted that they would refer patients
      themselves if there was a mandatory, nationally endorsed referral policy. These
      findings have implications for clinical practice and policy, and suggest that the
      formulation and implementation of robust national guidelines should be a
      priority. Because nurses would follow such guidelines, this might lead to an
      increase in donor rates and circumvent some uncertainty regarding referral.

PMID- 29025444
TI  - First report of clinical presentation of a bite by a running spider, Philodromus
      sp. (Araneae: Philodromidae), with recommendations for spider bite management.
AB  - This article describes the clinical progression of symptoms over a period of 5
      days of a bite inflicted by a Philodromus sp. spider. Commonly known as 'running
      spiders', these are not considered to be harmful to humans. This report, however,
      is the first description of an actual bite by a member of this group of spiders
      showing cytotoxic envenomation. Management of the bites should be as recommended
      for other cytotoxic spider bites.

PMID- 29025445
TI  - Blistering rash in a young male child.
AB  - A 3-year-old child was brought to the casualty department at Leratong Hospital,
      Johannesburg, South Africa, with severe bullous eruptions on the distal portions
      of both the upper and lower limbs. He had visited three different general
      practitioners prior to presentation and had been given several drugs and
      ointments, including three different classes of antibiotics. During his
      admission, the diagnosis of linear IgA bullous dermatitis was made. Dapsone and
      prednisone were given and he recovered well.

PMID- 29025446
TI  - Inefficient procurement processes undermine access to medicines in the Western
      Cape Province of South Africa.
AB  - BACKGROUND: South Africa (SA) has experienced several stock-outs of life-saving
      medicines for the treatment of major chronic infectious and non-communicable
      diseases in the public sector. OBJECTIVE: To identify the causes of stock-outs
      and to illustrate how they undermine access to medicines (ATM) in the Western
      Cape Province, SA. METHODS: This qualitative study was conducted with a sample of
      over 70 key informants (frontline health workers, sub-structure and provincial
      health service managers). We employed the critical incident technique to identify
      significant occurrences in our context, the consequences of which impacted on
      access to medicines during a defined period. Stock-outs were identified as one
      such incident, and we explored when, where and why they occurred, in order to
      inform policy and practice. RESULTS: Medicines procurement is a centralised
      function in SA. Health service managers unanimously agreed that stock-outs
      resulted from the following inefficiencies at the central level: (i) delays in
      awarding of pharmaceutical tenders; (ii) absence of contracts for certain
      medicines appearing on provincial code lists; and (iii) suppliers' inability to
      satisfy contractual agreements. The recurrence of stock-outs had implications at
      multiple levels: (i) health facility operations; (ii) the Chronic Dispensing Unit
      (CDU), which prepacks medicines for over 300 000 public sector patients; and
      (iii) community-based medicines distribution systems, which deliver the CDU's
      prepacked medicines to non-health facilities nearer to patient homes. For
      instance, stock-outs resulted in omission of certain medicines from CDU parcels
      that were delivered to health facilities. This increased workload and caused
      frustration for frontline health workers who were expected to dispense omitted
      medicines manually. According to frontline health workers, this translated into
      longer waiting times for patients and associated dissatisfaction. In some
      instances, patients were asked to return for undispensed medication at a later
      date, which could potentially affect adherence to treatment and therapeutic
      outcomes. Stock-outs therefore undermined the intended benefits of ATM
      strategies. CONCLUSION: Addressing the procurement challenges, most notably
      timeous tender awards and supplier performance management, is critical for
      successful implementation of ATM strategies.

PMID- 29025447
TI  - Enough is not enough: Medical students' knowledge of early warning signs of
      childhood cancer.
AB  - BACKGROUND: The reported incidence of childhood cancer in upper-middle-income
      South Africa (SA) is much lower than in high-income countries, partly due to
      under-diagnosis and under-reporting. Documented survival rates are disturbingly
      low, prompting an analysis of potential factors that may be responsible.
      OBJECTIVES: To determine final-year medical students' level of knowledge of early
      warning signs of childhood cancer and whether a correlation existed between test
      scores and participants' age, gender and previous exposure to a person with
      cancer. METHODS: A two-part questionnaire based on the Saint Siluan mnemonic,
      testing both recall and recognition of early warning signs of childhood cancer,
      was administered. The Mann-Whitney-Wilcoxon test was used to assess differences
      in continuous and count variables between demographic data, experience and
      responses, and Fisher's exact test and Spearman's rank correlation coefficient
      were used to determine correlations between demographic data, previous contact
      with persons with cancer and test scores. A novel equality ratio was calculated
      to compare the recall and recognition sections and allowed analysis of recall v.
      recognition. RESULTS: The 84 participants recalled a median of six signs each
      (interquartile range 4 - 7) and correctly recognised a median of 70% in the
      recognition section, considered a pass mark. There was no correlation between
      participants' age, gender, previous contact with a person with cancer and
      recognition scores. Students with previous exposure to a person with cancer had
      higher scores in the recall section, but this did not achieve statistical
      significance. Students were able to recognise more signs of haematological
      malignancies than central nervous system (CNS) malignancies. CONCLUSION: The
      study demonstrated a marked inconsistency between recall and recognition of signs
      of childhood cancer, with signs of CNS malignancies being least recognised.
      However, the majority of students could recognise enough early warning signs to
      meet the university pass standard. Although this study demonstrated acceptable
      recognition of early warning signs of childhood cancer at one university, we
      suggest that long-term recall in medical practitioners is poor, as reflected in
      the low age-standardised ratios of childhood cancer in SA. We recommend increased
      ongoing exposure to paediatric oncology in medical school and improved awareness
      programmes to increase early referrals.

PMID- 29025448
TI  - National South African HIV prevalence estimates robust despite substantial test
      non-participation.
AB  - BACKGROUND: South African (SA) national HIV seroprevalence estimates are of
      crucial policy relevance in the country, and for the worldwide HIV response.
      However, the most recent nationally representative HIV test survey in 2012 had
      22% test non-participation, leaving the potential for substantial bias in current
      seroprevalence estimates, even after controlling for selection on observed
      factors. OBJECTIVE: To re-estimate national HIV prevalence in SA, controlling for
      bias due to selection on both observed and unobserved factors in the 2012 SA
      National HIV Prevalence, Incidence and Behaviour Survey. METHODS: We jointly
      estimated regression models for consent to test and HIV status in a Heckman-type
      bivariate probit framework. As selection variable, we used assigned interviewer
      identity, a variable known to predict consent but highly unlikely to be
      associated with interviewees' HIV status. From these models, we estimated the HIV
      status of interviewed participants who did not test. RESULTS: Of 26 710
      interviewed participants who were invited to test for HIV, 21.3% of females and
      24.3% of males declined. Interviewer identity was strongly correlated with
      consent to test for HIV; declining a test was weakly associated with HIV
      serostatus. Our HIV prevalence estimates were not significantly different from
      those using standard methods to control for bias due to selection on observed
      factors: 15.1% (95% confidence interval (CI) 12.1 - 18.6) v. 14.5% (95% CI 12.8 -
      16.3) for 15 - 49-year-old males; 23.3% (95% CI 21.7 - 25.8) v. 23.2% (95% CI
      21.3 - 25.1) for 15 - 49-year-old females. CONCLUSION: The most recent SA HIV
      prevalence estimates are robust under the strongest available test for selection
      bias due to missing data. Our findings support the reliability of inferences
      drawn from such data.

PMID- 29025449
TI  - Incidence of chemotherapy-induced neutropenia in HIV-infected and uninfected
      patients with breast cancer receiving neoadjuvant chemotherapy.
AB  - BACKGROUND: Chemotherapy-induced neutropenia (CIN) can result in poor tolerance
      of chemotherapy, leading to dose reductions, delays in therapy schedules,
      morbidity and mortality. Actively identifying predisposing risk factors before
      treatment is of paramount importance. We hypothesised that chemotherapy is
      associated with a greater increase in CIN and its complications in HIV-infected
      patients than in those who are not infected. OBJECTIVE: To establish the
      incidence of CIN in HIV-infected and uninfected patients undergoing chemotherapy.
      METHODS: A retrospective chart review and analysis was conducted in the oncology
      departments at Inkosi Albert Luthuli Central Hospital and Addington Hospital,
      Durban, South Africa. The study population consisted of 65 previously untreated
      women of all ages with stage II - IV breast cancer and known HIV status treated
      with neoadjuvant chemotherapy from January 2012 to December 2015. RESULTS: HIV
      infected patients formed 32.3% of the group, and 95.2% of them were on
      antiretroviral therapy. The mean age (standard deviation (SD)) of the cohort was
      48.5 (13.2) years (40.6 (9.6) years for the HIV-infected group v. 52.0 (13.1)
      years for the uninfected group; p<0.001). Ninety-five neutropenia episodes were
      observed (rate 0.85 per 1 year of follow-up time). Following multivariate
      adjustment, patients with HIV infection were almost two times more likely to
      develop CIN (hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.06 - 2.92;
      p=0.029. A high baseline absolute neutrophil count (ANC) (HR 0.80, 95% CI 0.68 -
      0.95; p=0.005) remained significantly associated with protection against CIN.
      CONCLUSIONS: HIV-infected patients were younger than those who were not infected,
      and presented at a more locally advanced stage of disease. HIV infection was an
      independent predictor for CIN. HIV-infected patients had an almost two-fold
      increased risk of developing CIN and developed neutropenia at a much faster rate.
      A high baseline white cell count and ANC were protective against CIN.

PMID- 29025450
TI  - An increase in rates of obstetric haemorrhage in a setting of high HIV
      seroprevalence.
AB  - BACKGROUND: Obstetric haemorrhage (OH) is the leading cause of maternal mortality
      worldwide, although, indirectly, HIV is also a leading cause of maternal
      mortality in some settings with a high HIV seroprevalence. OBJECTIVE: To
      determine the possible association between increasing rates of OH and HIV or its
      treatment. METHODS: We conducted a retrospective chart review of women with OH at
      King Edward VIII Hospital, Durban, South Africa, over a 3-year period (2009 -
      2011), during which the drug regimen for the prevention of mother-to-child
      transmission was evolving from single-dose nevirapine to antenatal zidovudine
      combined with intrapartum nevirapine (also referred to as dual therapy), and
      finally to a combination or highly active antiretroviral therapy (cART or HAART).
      Cases of OH (including abruptio placentae, placenta praevia, unspecified
      antepartum haemorrhage (APH), and postpartum haemorrhage (PPH)) were identified
      from maternity delivery records, and the relevant data extracted. RESULTS: We
      analysed the records of 448 women diagnosed with OH. Even though the incidence of
      OH was low, the study found an increasing number of cases during the 3-year
      period. PPH - not APH - was associated with HIV seropositivity (odds ratio 1.84,
      95% confi-dence interval 1.14 - 2.95). cART was not associated with an increased
      risk of haemorrhage. CONCLUSION: HIV was associated with a high risk of PPH, and
      its possible association with HIV treatment needs further research.

PMID- 29025451
TI  - Mid-upper arm circumference: A surrogate for body mass index in pregnant women.
AB  - BACKGROUND: Nutrition in pregnancy has implications for both mother and fetus,
      hence the importance of an accurate assessment at the booking visit during
      antenatal care. The body mass index (BMI, kg/m2) is currently the gold standard
      for measuring body fatness. However, pregnancy-associated weight gain and oedema,
      as well as late booking in our population setting, cause concern about the
      reliability of using the BMI to assess body fat or nutritional status in
      pregnancy. The mid-upper arm circumference (MUAC) has been used for many decades
      to assess malnutrition in children aged <5 years. Several studies have also shown
      a strong correlation between MUAC and BMI in both pregnant and non-pregnant adult
      populations. OBJECTIVE: To assess the correlation between the MUAC and BMI in
      pregnant women booking for antenatal care in the Metro West area of Cape Town,
      South Africa. METHODS: We conducted a cross-sectional study of women booking at
      four midwife obstetric units. Anthropometric measurements (height, weight and
      MUAC) were carried out on pregnant women at their first antenatal booking visit.
      RESULTS: The results showed a strong correlation between MUAC and BMI in pregnant
      women up to 30 weeks' gestation. The correlation was calculated at 0.92 for the
      entire group. The MUAC cut-offs for obesity (BMI >30) and malnutrition (BMI
      <18.5) were calculated as 30.57 cm and 22.8 cm, respectively. CONCLUSION: MUAC
      correlates strongly with BMI in pregnancy up to a gestation of 30 weeks in women
      attending Metro West maternity services. In low-resource settings, the simpler
      MUAC measurement could reliably be substituted for BMI to assess nutritional
      status.

PMID- 29025452
TI  - Management of failed spinal anaesthesia for caesarean section.
AB  - BACKGROUND: Failed spinal anaesthesia for caesarean section (CS) may be partial
      or complete and the subsequent discomfort is the most commonly cited cause of
      litigation in obstetric anaesthesia. OBJECTIVES: To determine if there is a
      standardised approach to: (i) testing the level of block of spinal anaesthesia;
      and (ii) the management of failed spinal anaesthesia for CS. METHODS: A
      structured questionnaire to ascertain the current practice of testing the level
      of block and management of three different scenarios of failed spinal anaesthesia
      was distributed to 51 government hospitals in KwaZulu-Natal, South Africa (SA).
      All obstetric anaes-thetic service providers, ranging from interns to specialist
      anaesthetists, were invited to complete the questionnaire. RESULTS: A total of
      375 responses were received from 42 of the 51 hospitals surveyed. Specialist
      anaesthetists managed failure of spinal anaesthesia significantly differently
      than other anaesthetic service providers. Specialists were more likely to convert
      to a general anaesthetic (GA), while others were more likely to repeat spinal
      anaesthesia or administer intravenous ketamine, midazolam and opioids. Only 212
      respondents (56%) tested the level of block and there was no difference between
      the groups with regard to the method of assessment of height (p=0.15). Non
      specialists, however, accepted a significantly lower level of block, using
      pinprick, than specialists (p=0.027), which could lead to a higher failure rate.
      More than one-third of non-specialists did not consider themselves competent to
      perform a GA and >90% of respondents agreed that a 'failed' spinal algorithm
      would be useful. CONCLUSION: There is a need for standardised assessment of the
      adequacy of spinal anaesthesia for CS in SA, as well as a failed spinal
      algorithm.

PMID- 29025453
TI  - Interprofessional communication in organ transplantation in Gauteng Province,
      South Africa.
AB  - BACKGROUND: Communication is essential to the transplant process, but it is
      challenging in South Africa (SA) because of the complexity of the country and the
      health system, the nature of transplantation as a technical procedure with
      inherent psychological considerations, and the large number of professionals
      involved. Transplant communication has not been explored in SA, and this study
      was the first to use health communication methods to generate empirical evidence
      relating to it. OBJECTIVE: To explore communication in transplant settings in
      Gauteng Province, SA. METHODS: Qualitative methods were used to collect data
      across six hospitals and transplant centres in Gauteng. State and private
      institutions were equally represented. Health professionals and transplant co
      ordinators participated. Thematic analysis of data was undertaken. RESULTS:
      Facilitators of interprofessional transplant communication included appreciation
      of its importance to good practice and cohesive individual transplant teams.
      Barriers to interprofessional communication were observed when individual teams
      had to come together in a multi-team, interdisciplinary environment, when
      interchange became aggressive, and when information was not passed on to other
      health professionals timeously. These barriers had implications for continuity of
      care and ethics, which could lead to moral distress. CONCLUSION: Transplantation
      in Gauteng is characterised by aspects of good teamwork, and the importance of
      effective communication is acknowledged. Transplantation also faces some
      challenges in terms of interprofessional communication. Recommendations for
      mitigating some of the gaps include integrating a health communication specialist
      into the transplant process, 'knotworking', the use of apology, and an advance
      warning text-message system for transplant professionals.

PMID- 29025454
TI  - An audit of traumatic brain injury (TBI) in a busy developing-world trauma
      service exposes a significant deficit in resources available to manage severe
      TBI.
AB  - BACKGROUND: Traumatic brain injury (TBI) affects large numbers of patients, both
      adults and children, and significant resources are needed to manage it.
      OBJECTIVE: To determine the burden of TBI and the adequacy of available resources
      to manage in the Pietermaritzburg Metropolitan Trauma Service (PMTS). METHODS:
      All patients with a TBI were identified from the hybrid electronic medical
      registry at Grey's and Edendale hospitals in Pietermaritzburg (PMB), KwaZulu
      Natal, South Africa. Patients were classified according to severity of head
      injury and age. We defined mild TBI as Glasgow coma scale (GCS) 13 - 15, moderate
      as GCS 9 - 12, and severe as GCS <=8, in accordance with international standards.
      We divided the cohort according to ages 0 - 5 years, 6 - 10 years, >10 - 17 years
      and adults (>17 years). RESULTS: From January 2012 to December 2014, 3 301
      patients were treated for TBI in PMB. The mean age was 27.4 (standard deviation
      14.4) years. There were 2 632 males and 564 females. There were 2 540 mild, 326
      moderate, and 329 severe TBI admissions during the period under review. A total
      of 139 (4.2%) patients died. A total of 242 (7.3%) patients were admitted to the
      intensive care unit (ICU), of whom 137 (57.0%) had a GCS of <=9. Only 27.0% of
      patients with a GCS of <=9 were admitted to the ICU. CONCLUSION: There is a
      significant burden of TBI managed by the PMTS. Critical care resources available
      to manage patients with TBI are inadequate.

PMID- 29025455
TI  - The burden of gunshot injuries on orthopaedic healthcare resources in South
      Africa.
AB  - BACKGROUND: Injuries inflicted by gunshot wounds (GSWs) are an immense burden on
      the South African (SA) healthcare system. In 2005, Allard and Burch estimated SA
      state hospitals treated approximately 127 000 firearm victims annually and
      concluded that the cost of treating an abdominal GSW was approximately USD1 467
      per patient. While the annual number of GSW injuries has decreased over the past
      decade, an estimated 54 870 firearm-related injuries occurred in SA in 2012. No
      study has estimated the burden of these GSWs from an orthopaedic perspective.
      OBJECTIVE: To estimate the burden and average cost of treating GSW victims
      requiring orthopaedic interventions in an SA tertiary level hospital. METHODS:
      This retrospective study surveyed more than 1 500 orthopaedic admissions over a
      12-month period (2012) at Groote Schuur Hospital, Cape Town, SA. Chart review
      subsequently yielded data that allowed analysis of cost, theatre time, number and
      type of implants, duration of admission, diagnostic imaging studies performed,
      blood products used, laboratory studies ordered and medications administered.
      RESULTS: A total of 111 patients with an average age of 28 years (range 13 - 74)
      were identified. Each patient was hit by an average of 1.69 bullets (range 1 -
      7). These patients sustained a total of 147 fractures, the majority in the lower
      extremities. Ninety-five patients received surgical treatment for a total of 135
      procedures, with a cumulative surgical theatre time of >306 hours. Theatre costs,
      excluding implants, were in excess of USD94 490. Eighty of the patients received
      a total of 99 implants during surgery, which raised theatre costs an additional
      USD53 381 cumulatively, or USD667 per patient. Patients remained hospitalised for
      an average of 9.75 days, and total ward costs exceeded USD130 400. Individual
      patient costs averaged about USD2 940 (ZAR24 945) per patient. CONCLUSION: This
      study assessed the burden of orthopaedic firearm injuries in SA. It was estimated
      that on average, treating an orthopaedic GSW patient cost USD2 940, used just
      over 3 hours of theatre time per operation, and necessitated a hospital bed for
      an average period of 9.75 days. Improved understanding of the high incidence of
      orthopaedic GSWs treated in an SA tertiary care trauma centre and the costs
      incurred will help the state healthcare system better prioritise orthopaedic
      trauma funding and training opportunities, while also supporting cost-saving
      measures, including redirection of financial resources to primary prevention
      initiatives.

PMID- 29025456
TI  - A finger or not? Prostate examinations by non-urologists at a South African
      academic institution.
AB  - BACKGROUND: According to the South African (SA) National Cancer Registry 2009,
      prostate cancer is the most commonly diagnosed solid-organ cancer in SA men: the
      incidence increases at ~3% every year, with 1/26 men developing prostate cancer
      in their lifetime and five men dying every day. Screening for prostate cancer by
      performing a digital rectal examination (DRE) adds to the sensitivity and
      specificity of serum prostate-specific antigen (PSA) testing and is an important
      component of the assessment for the early detection of prostate cancer.
      OBJECTIVES: To ascertain whether doctors who are not in the field of urology
      perform DREs and PSA testing to screen for prostate cancer, where indicated, and
      to determine the reason, if any, why doctors do not perform prostate
      examinations. METHODS: Doctors (including specialists and primary care
      practitioners) who consulted adult male patients in the emergency departments and
      polyclinics of three academic hospitals were included in the sample and asked to
      complete an anonymous questionnaire. Doctors with specialist urological training
      were excluded from the sample. The questionnaire included the following aspects:
      gender, year of graduation and university, current position, knowledge of PSA
      screening and DRE, whether these were being performed, and reasons for non
      performance. RESULTS: The response rate was 303/350 participants. Fifty-nine
      percent of the respondents were female. The median duration of experience was 5
      years. The mean (standard deviation) knowledge score with regard to screening was
      56.1% (20). The PSA test alone was most frequently done (35%), followed by asking
      the patient about urinary tract symptoms (28%). In contrast, DRE of the prostate,
      alone or combined with a PSA test, was performed less frequently (13.2% and
      10.6%, respectively). Some of the most common reasons for not performing a DRE
      included: 'It's more convenient to do a PSA test'; 'Urologists will examine the
      prostate anyway'; 'No privacy in the emergency department/admission ward';
      'Prostate exam is not relevant to my practice'; 'There is not enough time'; and
      'The practitioner forgets'. Doctors with >7 years of working experience are the
      least likely to do a DRE. CONCLUSION: Performance rates of DRE and PSA testing by
      doctors who are not urologists are very low, which may have significant clinical
      implications. It is recommended that SA prostate cancer screening guidelines are
      necessary to change practice with regard to this condition.

PMID- 29025458
TI  - Editorial.

PMID- 29025457
TI  - Characteristics and correlates of alcohol consumption among adult chronic care
      patients in North West Province, South Africa.
AB  - BACKGROUND: Alcohol consumption patterns in South Africa (SA) tend to be
      characterised by risky patterns of drinking. Taken together with the large burden
      of disease associated with HIV and tuberculosis (TB), heavy alcohol consumption
      patterns with these chronic conditions has the potential to compromise the
      efficacy of treatment efforts among such patients. OBJECTIVE: To explore the
      characteristics, correlates and diagnoses of alcohol use disorders among chronic
      care patients in SA. METHOD: A cross-sectional survey was conducted in three
      public health clinic facilities in the North West Province of SA. A total of 1
      322 patients were recruited from non-emergency waiting areas. RESULTS:
      Proportions of patients with abstinence, hazardous, harmful and dependent
      consumption were determined using logistic regression. Of the patients screened,
      nearly half (45%) drank alcohol and, of these, 10% were classified as hazardous
      drinkers, 1.7% as harmful drinkers, and 1.6% as dependent drinkers (overall 3%
      alcohol use disorder). Abstinence proportions were 60% and 38% among women and
      men, respectively. Alcohol Use Disorders Identification Test scores for men were
      63% higher than for women. The lowest patient abstinence proportion (47%) and
      highest dependent drinking (10%) was for TB. The highest abstinence proportion
      was for diabetes (65%), and the highest hazardous and harmful drinking was among
      TB (14%) and HIV (7%) patients. CONCLUSIONS: The high levels of risky drinking
      among chronic care patients, particularly among patients receiving treatment for
      HIV and TB, are concerning. Instituting appropriate screening measures and
      referral to treatment would be an important first step in mitigating the effects
      of risky alcohol use among chronic care patients.

PMID- 29025460
TI  - Allergies in Asia-Pacific survey.

PMID- 29025459
TI  - Nasal allergies in the Middle Eastern population: Results from the "Allergies in
      Middle East Survey".
AB  - BACKGROUND: Chronic respiratory diseases such as asthma and allergic rhinitis
      (AR) are a major public health problem in developing countries including those in
      the Middle East. However, to date, there is a paucity of information related to
      physician-diagnosed AR in this region. The Allergies in Middle East Survey was
      undertaken to help clarify and broaden the understanding of physician-diagnosed
      AR across Egypt, Iran, Lebanon, Saudi Arabia, and the United Arab Emirates. The
      survey explores the frequency of physician-diagnosed AR, prevalence and types of
      associated symptoms, the impact on quality of life (QOL), current treatment
      practices, and therapy expectations. METHODS: In total, 7411 households in five
      countries (Egypt, Lebanon, Saudi Arabia, Iran and the United Arab Emirates) were
      screened to identify individuals that were >=4 years old with a physician
      diagnosis of AR and either symptoms and/or treatment in the past 12 months. A
      total of 501 respondents from the five countries completed the survey.
      Standardized questionnaires were used to make comparisons across the regions;
      however, the data collection procedures were tailored for each country. The
      sample was probability based to ensure valid statistical inference to the
      population. RESULTS: Ten percent of the Middle East population surveyed had a
      physician diagnosis of AR, with 65% of respondents stating that their allergies
      were intermittent in nature. An otolaryngologist or allergist diagnosed the
      majority of the individuals surveyed. Runny nose, nasal and throat itching,
      postnasal drip, and nasal congestion or stuffed up nose were the most common and
      bothersome symptoms of AR. The majority of survey participants (58% of the
      overall survey population) with AR reported that the condition had an impact on
      their daily private and professional life. Seventy-two percent of adults reported
      that their AR symptoms limited their work/school activities and 35% reported that
      their AR interfered with and caused them to miss work or school within the past
      12 months. One factor, in addition to the outward AR symptoms, that could have
      contributed to these function impairments may have been sleep disturbances.
      Although a secondary symptom to AR, sleep disturbances (difficulty getting to
      sleep, waking up during the night or lack of a good night's sleep) were shown in
      this survey to be extremely troubling in ~15% of AR sufferers. In the past year
      >90% of patients reported taking a medication of any type for their AR, with
      nearly a 4:1 ratio of patients taking a prescription medication versus an over
      the-counter (OTC) medication in the past 4 weeks. Over 75% of survey respondents
      reported taking an intranasal corticosteroid (INCS) in the last 4 weeks and the
      satisfaction rate of INCS medications was similar to that reported for OTC
      medications. The most common reasons cited for dissatisfaction with INCS
      medications were inadequate effectiveness, bothersome side effects (e.g.,
      unpleasant taste and retrograde drainage into the pharynx), decreased
      effectiveness with chronic use, and failure to provide 24-hour relief.
      CONCLUSION: These data show that AR is common in the Middle East region as
      elsewhere in the world. Many patients with AR in Middle East region suffer from
      their symptoms (e.g., runny nose, nasal itching, nasal congestion, postnasal
      drip, and other symptoms) on all or most days during the times of the year that
      their allergies are worst. These symptoms have been shown to reduce QOL and
      performance at work/school to a significant degree. Additionally, the survey data
      underscore a considerable treatment gap with current therapies for AR and that
      many AR patients still have not found adequate effectiveness with currently
      available medications. Thus, through identification of disease impact on the
      Middle East population and highlighting treatment gaps, clinicians in the Middle
      East may better understand and treat AR, leading to improvements in overall
      patient satisfaction and QOL.

PMID- 29025461
TI  - Nasal allergies in the Asian-Pacific population: Results from the Allergies in
      Asia-Pacific Survey.
AB  - BACKGROUND: The Allergies in Asia-Pacific Survey describes the symptoms, impact,
      and treatment of allergic rhinitis (AR) across Australia, China, Hong Kong,
      Malaysia, Singapore, Taiwan, Vietnam, and the Philippines. The Allergies in Asia
      Pacific Survey was undertaken to further clarify the prevalence of physician
      diagnosed nasal allergies (NAs), impact on quality-of-life (QOL), existing
      treatment paradigms and gaps, and NA medications currently used in treatment.
      METHODS: Thirty-three thousand three hundred seventy-eight households were
      screened for individuals, >=4 years old, with a physician diagnosis of AR or NA
      and either symptoms or treatment in the past 12 months. Standardized
      questionnaires were used to make comparisons across regions. A total of 1043
      adults and 192 children were included in the survey. RESULTS: Nine percent of
      participants were diagnosed with AR with two of three responding that their NAs
      were seasonal in nature. Nasal congestion was the most common and bothersome
      symptom of AR. Most participants reported that AR impacted their QOL with nearly
      one-half citing impairments in school/work performance/productivity. Sleep
      disturbances, secondary to AR, were also shown to be appreciable. Two-thirds of
      patients took medication for their AR. Less than one-quarter of survey
      respondents reported taking an intranasal corticosteroid and the satisfaction
      rate was similar to that of over-the-counter medications. The most common reasons
      cited for dissatisfaction were related to inadequate efficacy and bothersome side
      effects. CONCLUSION: AR appears to be extremely common across Asia-Pacific
      nations. Many individuals with AR suffer from symptoms that reduce QOL and
      treatment gaps exist with current therapies. Through identification of disease
      impact and highlighting treatment gaps, clinicians may better understand and
      treat AR, leading to improvements in overall patient satisfaction and QOL.

PMID- 29025462
TI  - Mechanism of action of allergen immunotherapy.
AB  - BACKGROUND: Allergen immunotherapy (AIT) leads to the production of antiallergen
      immunoglobulin (IgG) or "blocking antibody" in the serum and an increase in
      antiallergen IgG and IgA in nasal secretions. There is also a decrease in the
      usual rise in antiallergen IgE that occurs after the pollen season. METHODS: In
      this paper, mechanisms of action of allergen immunotherapy is reviewed. RESULTS:
      Regulatory T (Treg) cells and their cytokines, primarily interleukin (IL) 10 and
      transforming growth factor beta, suppress T-helper type 2 immune responses and
      control allergic diseases in many ways. AIT induces a shift in the proportion of
      IL-4-secreting T-helper type 2 cells in favor of IL-10-secreting inducible Treg
      cells specific for the same allergenic epitope that increases in number and
      function. Different types of inducible Treg control several facets of allergic
      inflammation. There are two main types of immunotherapy: subcutaneous
      immunotherapy and sublingual immunotherapy. Subcutaneous immunotherapy is
      efficacious and is indicated for the reduction of seasonal symptoms. Sublingual
      immunotherapy involves the regular self-administration and retention of allergen
      extract under the tongue for 1-2 minutes before the extract is swallowed. The
      allergens cross the mucosa in 15-30 minutes and are then captured by tolerogenic
      dendritic cells and processed as small peptides. Next, via the lymphatic system,
      a systemic immune response is created to produce an early decrease in mast cell
      and basophil degranulation. CONCLUSION: AIT is indicated for the treatment of
      moderate-to-severe intermittent or persistent symptoms of allergic rhinitis. AIT
      can be administered to those >5 years of age and has been shown to be safe in
      children as young as 3 years of age. In this article, AIT and other types of
      immunotherapies were discussed as well as the indications for immunotherapy.

PMID- 29025463
TI  - Clinical efficacy of immunotherapy in allergic rhinitis.
AB  - BACKGROUND: Aeroallergen immunotherapy (AIT) should be considered for patients
      who exhibit symptoms of allergic rhinitis (AR), rhinoconjunctivitis, and/or
      asthma after natural exposure to allergens and who also demonstrate specific
      immunoglobulin E antibodies against relevant allergens. METHODS: In this paper,
      clinical efficacy of immunotherapy in allergic rhinitis is reviewed. RESULT:
      Subcutaneous allergen immunotherapy (SCIT) is effective for seasonal and
      perennial AR. Sustained effectiveness requires several years of treatment. SCIT
      may prevent the development of allergic asthma in children with AR. Sublingual
      allergen immunotherapy (SLIT) is currently considered an alternative treatment to
      the subcutaneous route. The use of SLIT has been included in international
      guidelines for the treatment of AR with or without conjunctivitis. CONCLUSION:
      Patients treated with SCIT are at risk of both local and systemic adverse
      reactions; however, in most cases, symptoms are readily reversible if they are
      recognized early and treated promptly. The safety profile of SLIT is good;
      therefore, SLIT can be self-administered by patients in their homes. In this
      article, we reviewed the efficacy and safety of allergen immunotherapy.

PMID- 29025464
TI  - Alternative products to treat allergic rhinitis and alternative routes for
      allergy immunotherapy.
AB  - BACKGROUND: Some alternative products instead of immunotherapy are used in
      patients with allergic rhinitis (AR). METHODS: In this paper, alternative
      products to treat allergic rhinitis and alternative routes for allergy
      immunotherapy are reviewed. RESULTS: Alternative products and methods used
      instead of immunotherapy are tea therapy, acupuncture, Nigella sativa, cinnamon
      bark, Spanish needle, acerola, capsaicin (Capsicum annum), allergen-absorbing
      ointment, and cellulose powder. N. sativa has been used in AR treatment due to
      its anti-inflammatory effects. N. sativa oil also inhibits the cyclooxygenase and
      5-lipoxygenase pathways of arachidonic acid metabolism. The beneficial effects of
      N. sativa seed supplementation on the symptoms of AR may be due to its
      antihistaminic properties. To improve the efficacy of immunotherapy, some
      measures are taken regarding known immunotherapy applications and alternative
      routes of intralymphatic immunotherapy and epicutaneous immunotherapy are used.
      CONCLUSION: There are alternative routes and products to improve the efficacy of
      immunotherapy.

PMID- 29025465
TI  - The creation and verification of cranial models using three-dimensional rapid
      prototyping technology in field of transnasal sphenoid endoscopy.
AB  - BACKGROUND: Surgical navigation systems have been used increasingly in guiding
      complex ear, nose, and throat surgery. Although these are helpful, they are only
      beneficial intraoperatively; thus, the novice surgeon will not have the
      preoperative training or exposure that can be vital in complex procedures. In
      addition, there is a lack of reliable models to give surgeons hands-on training
      in performing such procedures. METHODS: A technique using an industrial rapid
      prototyping process by three-dimensional (3D) printing was developed, from which
      accurate spatial models of the nasal cavity, paranasal sinuses (sphenoid sinus in
      particular), and intrasellar/pituitary pathology were produced, according to the
      parameters of an individual patient. Image-guided surgical (IGS) techniques on
      two different platforms were used during endoscopic transsphenoidal surgery to
      test and validate the anatomical accuracy of the sinus models by comparing the
      models with radiological images of the patient on IGS. RESULTS: It was possible
      to register, validate, and navigate accurately on these models using commonly
      available navigation stations, matching accurately the anatomy of the model to
      the IGS images. CONCLUSION: These 3D models can be reliably used for
      teaching/training and preoperative planning purposes.

PMID- 29025466
TI  - Long-term Results of Bilateral Endoscopic Vidian Neurectomy in the Management of
      Moderate to Severe Persistent Allergic Rhinitis.

PMID- 29025467
TI  - Nasal eosinophilia and serum soluble intercellular adhesion molecule 1 in
      patients with allergic rhinitis treated with montelukast alone or in combination
      with desloratadine or levocetirizine.
AB  - BACKGROUND: Because intercellular adhesion molecule (ICAM) 1 and recruitment of
      eosinophils are crucial in supporting allergic inflammation, their down
      regulation may bring additional benefits in patients' recovery. We have assessed
      nasal eosinophilia and serum soluble ICAM-1 (sICAM-1) concentrations in relation
      to nasal symptoms in patients with persistent allergic rhinitis (AR) treated for
      6 weeks with either desloratadine, levocetirizine, montelukast alone, or in
      combination. METHODS: In this single-center, randomized, double-blind, placebo
      controlled, crossover, two-arm study, 40 patients with persistent AR were
      randomized to receive either montelukast and/or levocetirizine or placebo (n =
      20) or to receive treatment with montelukast and/or desloratadine or placebo (n =
      20). Nasal eosinophilia and concentration of sICAM-1 in peripheral blood were
      assessed before and on the last day of each treatment period. RESULTS: All active
      treatments in both arms of the study resulted in the decrease of sICAM-1 and
      nasal eosinophilia, which correlated with the severity of nasal symptoms. In the
      montelukast/levocetirizine arm, montelukast decreased nasal eosinophilia more
      significantly than levocetirizine, whereas in reduction of sICAM-1 all active
      treatment options were equally effective. However, in the
      desloratadine/montelukast arm, the resulting improvement of combination therapy
      of sICAM-1 and the influx of eosinophils was not statistically significant.
      CONCLUSION: The improvement of nasal symptoms in patients with AR treated with
      antihistamines, with or without montelukast, may additionally result from the
      reduction of sICAM-1 and nasal eosinophilia. Because the combination therapy may
      bring inconclusive benefits in this area there is a strong need of further
      studies to find mechanisms that favor combination therapy.

PMID- 29025468
TI  - Comparison of Clinical Data, CT, and Bone Histopathology in Unilateral Chronic
      Maxillary Sinusitis.

PMID- 29025469
TI  - Abstracts presented at the North American Rhinology & Allergy Conference, January
      31-February 3, 2013, Puerto Rico.

PMID- 29025470
TI  - Uncontrolled asthma: A real-life experience.

PMID- 29025471
TI  - Enhancing sublingual immunotherapy by systemic or local factors: A role for
      vitamin D and lingual tonsil?

PMID- 29025472
TI  - Computed nasal resistance compared with patient-reported symptoms in surgically
      treated nasal airway passages: A preliminary report.
AB  - BACKGROUND: Nasal airway obstruction (NAO) is a common health condition impacting
      mood, energy, recreation, sleep, and overall quality of life. Nasal surgery often
      addresses NAO but the results are sometimes unsatisfactory. Evaluating surgical
      treatment efficacy could be improved if objective tests were available that
      correlated with patient-reported measures of symptoms. The goal of this study was
      to develop methods for comparing nasal resistance computed by computational fluid
      dynamics (CFD) models with patient-reported symptoms of NAO using early data from
      a 4-year prospective study. METHODS: Computed tomography (CT) scans and patient
      reported scores from the Nasal Obstruction Symptom Evaluation (NOSE) scale and a
      visual analog scale (VAS) measuring unilateral airflow sensation were obtained
      pre- and postoperatively in two NAO patients showing no significant mucosal
      asymmetry who were successfully treated with functional nasal surgery, including
      septoplasty. Pre- and postsurgery CFD models were created from the CT scans.
      Numerical simulation of steady-state inspiratory airflow was used to calculate
      bilateral and unilateral CFD-derived nasal resistance (CFD-NR). RESULTS: In both
      subjects, NOSE and VAS scores improved after surgery, bilateral CFD-NR decreased,
      and unilateral CFD-NR decreased on the affected side. In addition, NOSE and VAS
      scores tracked with unilateral CFD-NR on the affected side. CONCLUSION: These
      preliminary results suggest a possible correlation between unilateral NR and
      patient-reported symptoms and imply that analysis of unilateral obstruction
      should focus on the affected side. A formal investigation of unilateral CFD-NR
      and patient-reported symptoms in a series of NAO patients is needed to determine
      if these variables are correlated.

PMID- 29025473
TI  - Dietary polyphenols affect MUC5AC expression and ciliary movement in respiratory
      cells and nasal mucosa.

PMID- 29025474
TI  - Reply.

PMID- 29025475
TI  - Pseudomeningoceles of the sphenoid sinus masquerading as sinus pathology.

PMID- 29025476
TI  - Intracranial mucocele formation in the context of longstanding chronic
      rhinosinusitis: A clinicopathologic series and literature review.
AB  - Chronic rhinosinusitis (CRS) can lead to serious long-term adverse sequelae,
      particularly if left untreated. The aim of this study was to describe a series of
      intracranial mucoceles (ICMs) that arose in the context of longstanding CRS
      combined with a review of the pertinent literature. A retrospective chart review
      was performed on all patients who developed ICMs in association with CRS between
      2003 and 2012. The clinical presentation, radiographic features, surgical
      approach, intraoperative findings, and patient outcome were examined in the
      context of a literature review. Sixty-five cases of mucoceles were identified in
      patients with a history of CRS, of which seven (10.8%) were intracranial. Five
      patients were men and two were women with a mean age of 42.1 years. Headache,
      facial pressure, retro-orbital pain, and visual disturbances were the most common
      presenting symptoms. Five of the seven had previously undergone sinonasal
      surgery. Imaging studies showed ICMs involving the anterior cranial fossa, two of
      which were bilateral. Latency between onset of CRS and ICM detection ranged from
      3 to 19 years (mean, 9.4 years). All patients underwent endoscopic transnasal
      drainage with three also requiring a concurrent, open neurosurgical procedure to
      access the intracranial component. There were no postoperative complications, and
      no recurrences were observed after a mean follow-up of 2.7 years. ICMs presenting
      as delayed complications of CRS are uncommon and constitute a surgical challenge.
      Open, external skull base approaches used in conjunction with transnasal
      endoscopic drainage procedures may be necessary to achieve successful management
      of this rare condition.

PMID- 29025477
TI  - TB stigma: clearing the fog.

PMID- 29025478
TI  - Ending TB-related stigma and discrimination.

PMID- 29025479
TI  - Measuring TB-related stigma.

PMID- 29025480
TI  - Correlates of observing and willingness to report stigma towards HIV clients by
      (TB) health workers in Africa.
AB  - SETTING: Health care facilities in Kenya, Tanzania and Namibia. OBJECTIVE: To
      study the factors associated with the observation of and willingness to report
      stigmatising behaviour towards persons living with the human immunodeficiency
      virus (HIV) among health care workers (HCWs). DESIGN: Mixed-effect logistic
      regression analyses of 9516 HCW interviews, including those of 4062 (43%) TB
      workers carried out as part of the Service Provision Assessments (SPAs) between
      2006 and 2010. RESULT: Discrimination (i.e., enacted stigma) was observed by
      respectively 1042 (60%), 384 (40%) and 907 (69%) TB workers in Kenya, Namibia and
      Tanzania, similar to the trend observed among all HCWs. Observations of
      discrimination were clustered at facility level in Kenya, and mapping of facility
      level discrimination suggested geographic clustering. HCWs were more likely to
      observe discrimination in facilities without regular supportive supervision
      (adjusted OR [aOR] 2.33, 95%CI 1.09-4.96). No HCW characteristics were found to
      predict intention to report. Training in patients' rights and in confidentiality
      predisposed HCWs to recognise discrimination (aOR 2.51, 95%CI 1.19-5.28) and the
      willingness to report it (aOR 2.23, 95%CI 1.11-4.47). Exposure to training in TB
      infection control (IC) was associated with greater willingness to report
      discrimination (aOR 2.13, 95%CI 1.03-4.39). CONCLUSION: Supervision and exposure
      to training in patient's rights and confidentiality improved HCWs' understanding
      and advocacy of dignified and respectful TB-HIV care. All HCWs are equally likely
      to be allies, agents of change and amplifiers of an anti-stigma message, and
      broad engagement is required. Innovative approaches to reduce discrimination
      while ensuring proper IC-should be explored.

PMID- 29025481
TI  - Measuring HIV- and TB-related stigma among health care workers in South Africa: a
      validation and reliability study.
AB  - SETTING: Recent evidence indicates that human immunodeficiency virus (HIV) and
      tuberculosis (TB) related stigma act as a key barrier to the utilisation of
      associated occupational health services by South African health care workers
      (HCWs). It also highlights a dearth of appropriate tools to measure HIV and TB
      stigma among HCWs. OBJECTIVE: To test four scales measuring different aspects of
      stigma: respondent's external stigma (RES) and others' external stigma (OES)
      towards TB as well as HIV across different professional categories of HCWs.
      DESIGN: The current study employs data from a study on HIV and TB stigma among
      HCWs, a cluster randomised controlled trial for the collection of data among 882
      HCWs in the Free State Province of South Africa. Confirmatory factor analyses and
      structural equation modelling were used to assess the validity and reliability of
      the scales. RESULTS: All four scales displayed adequate internal construct
      validity. Subsequent analysis demonstrated that all four scales were metric
      invariant, and that the OES scales were even scalar-invariant across patient and
      support staff groups. The scales displayed good reliability and external
      construct validity. CONCLUSION: Our results support the use of the scales
      developed to measure TB and HIV stigma among HCWs. Further research is, however,
      needed to fine tune the instruments and test them across different resource
      limited countries.

PMID- 29025482
TI  - TB and HIV stigma compounded by threatened masculinity: implications for TB
      health-care seeking in Malawi.
AB  - SETTING: Urban Blantyre, Malawi. OBJECTIVE: To understand why men with
      tuberculosis (TB) in the community remain undiagnosed. DESIGN: A multi-method
      qualitative study applying a modified grounded theory approach. Data were
      gathered from March 2011 to March 2012 from 134 men and women taking part in 1)
      focus group discussions with community members (n = 6) and health care workers (n
      = 2), and 2) in-depth interviews with TB patients (n = 20, females n = 14) and
      chronic coughers (n = 20, women n = 8). Data were analysed inductively to
      identify, refine and consolidate, and verify emerging concepts and themes.
      RESULTS: Two emerging themes highlighting compound stigma in this high human
      immunodeficiency virus (HIV) prevalence, low-income setting are presented. First,
      cough or any illness that portended a 'serious' condition were accompanied by
      portrayals of cough, TB and HIV as being interchangeable. Chronic coughers and TB
      patients described their illness in ways that foregrounded bodily decimation and
      rupture of social life and masculine identity. Second, 'resistance strategies'
      entailed resisting classification as (seriously) ill by evading or ambivalently
      approaching health care, or acknowledging the 'ill' status then actively pursuing
      health-appropriate behaviours, including changing lifestyle or adopting non
      normative gender roles. CONCLUSIONS: Managing patients requires 1) going beyond
      syndromic management based on vital signs and clinical indicators to recognising
      and intervening on health care-seeking related tensions to retain individuals in
      care, and 2) understanding and addressing TB stigma as it manifests and affects
      men and women differently in specific settings.

PMID- 29025484
TI  - 'It makes the patient's spirit weaker': tuberculosis stigma and gender
      interaction in Dar es Salaam, Tanzania.
AB  - SETTING: Dar es Salaam, Tanzania. OBJECTIVES: To describe tuberculosis (TB)
      related stigma and to understand how it interacts with gender to affect access to
      care. DESIGN: Eight focus group discussions were held among 48 TB patients and
      their household members, and a thematic content analysis was carried out.
      RESULTS: The main components of stigma were fear, self-isolation, ostracization,
      loss of status in the community, and discrimination by providers. Participants
      described the cultural context in which stigma operated as characterized by a
      general lack of health knowledge, cultural beliefs about TB, and engendered
      beliefs about disease in general. Both genders described some similar effects of
      stigma, including relationship difficulties and specifically challenges forming
      new relationships, but many effects of stigma were distinct by gender: women
      described challenges including assumptions about promiscuity and infidelity, as
      well as rejection by partners, while men described survival challenges. Stigma
      acted as a barrier to care through a cyclical pattern of stigma and fear, leading
      to health-seeking delays, with resulting continued transmission and poor health
      outcomes that further reinforced stigma. CONCLUSION: TB-related stigma is
      prevalent in this setting and operates differently for men and women.
      Interventions designed to increase case detection must address stigma and its
      interaction with gender.

PMID- 29025483
TI  - Depressive symptoms and hazardous/harmful alcohol use are prevalent and correlate
      with stigma among TB-HIV patients in Lesotho.
AB  - SETTING: Limited data exist on the prevalence and correlates, including stigma,
      of mental health conditions, including depressive symptoms and alcohol use, among
      patients co-infected with tuberculosis (TB) and the human immunodeficiency virus
      (HIV) in sub-Saharan Africa, despite their negative impact on health outcomes.
      OBJECTIVE: To assess the prevalence and correlates of depressive symptoms and
      hazardous/harmful alcohol use among TB-HIV patients in the Start TB patients on
      ART and Retain on Treatment (START) study. DESIGN: START, a mixed-methods cluster
      randomized trial, evaluated a combination intervention package vs. standard of
      care (SOC) to improve treatment outcomes in TB-HIV co-infected patients in
      Lesotho. Moderate/severe depressive symptoms and hazardous/harmful alcohol use
      were measured using baseline questionnaire data collected from April 2013 to
      March 2015. Demographic, psychosocial, and TB- and HIV-related knowledge and
      attitudes, including stigma, were assessed for association with both conditions
      using generalized linear mixed models. RESULTS: Among 371 participants, 29.8%
      reported moderate/severe depressive symptoms, and 24.7% reported
      hazardous/harmful alcohol use; 7% reported both. Depressive symptoms were
      significantly associated with less education, more difficulty understanding
      written medical information, non-disclosure of TB, greater TB stigma, and the SOC
      study arm. Hazardous/harmful alcohol use was significantly associated with male
      sex, as well as greater TB and external HIV stigma. CONCLUSION: Prevalence of
      depressive symptoms and hazardous/harmful alcohol use were high, suggesting a
      need for routine screening for, and treatment of, mental health disorders in TB
      HIV patients.

PMID- 29025485
TI  - Secondary analysis of tuberculosis stigma data from a cluster randomised trial in
      Zambia and South Africa (ZAMSTAR).
AB  - SETTING: Zambian and South African TB and HIV Reduction (ZAMSTAR) cluster
      randomised trial (CRT) communities, 2006-2009. OBJECTIVES: To develop TB stigma
      items, and evaluate changes in them in response to a household intervention aimed
      at reducing TB transmission and prevalence but not tailored to reduce stigma.
      DESIGN: TB stigma was measured at baseline and 18 months later among 1826
      recently diagnosed TB patients and 1235 adult members of their households across
      24 communities; 12 of 24 communities were randomised to receive the household
      intervention. We estimated the impact of the household intervention on TB stigma
      using standard CRT analytical methods. RESULTS: Among household members,
      prevalence of blame and belief in transmission myths fell in both study arms over
      time: adjusted prevalence ratios (aPRs) comparing the household intervention with
      the non-household intervention arm were respectively 0.61 (95%CI 0.26-1.44) and
      0.77 (95%CI 0.48-1.25) at 18-month follow-up. Among TB patients, at baseline a
      low percentage experienced social exclusion and poor treatment by health staff
      and a relatively high percentage reported 'being made fun of', with little change
      over time. Disclosure of TB status increased over time in both study arms.
      Internalised stigma was less prevalent in the household arm at both baseline and
      follow-up, with an aPR of 0.85 (95%CI 0.41-1.76). Variability in stigma levels
      between countries and across communities was large. CONCLUSION: Robust TB stigma
      items were developed. TB stigma was not significantly reduced by the household
      intervention, although confidence intervals for estimated intervention effects
      were wide. We suggest that stigma-specific interventions are required to
      effectively address TB stigma.

PMID- 29025486
TI  - Using 15 DHS surveys to study epidemiological correlates of TB courtesy stigma
      and health-seeking behaviour.
AB  - SETTING: Tuberculosis (TB) stigma is thought to delay or prevent the decision to
      seek health care, but the strength of this association and the prevalence of
      anticipated TB stigma in the general population in most countries is unknown.
      OBJECTIVE: To examine epidemiological, cultural and sociodemographic factors
      associated with TB courtesy stigma in 15 surveys across 13 countries, and its
      link to health seeking for cough in children under five. DESIGN: A multilevel
      survey weighted logistic regression model was used to analyse how individual
      characteristics and social contexts affect the occurrence of TB courtesy stigma.
      The same modelling approach was used to analyse associations between TB courtesy
      stigma and individual-level predictors of health-seeking behaviour of mothers for
      children with cough. RESULTS: TB courtesy stigma varies greatly among countries.
      TB courtesy stigma was negatively correlated with knowledge of TB's curability
      (adjusted OR [aOR] 0.82; 95%CI 0.78-0.86) and human immunodeficiency virus (HIV)
      accepting attitudes (proxy for HIV stigma) (aOR 0.15, 95%CI 0.15-0.16). Mothers'
      health-seeking behaviour for children under five with cough was found to be
      positively correlated with HIV accepting attitudes (OR 1.16, 95%CI 1.08-1.25),
      but was marginally affected by TB courtesy stigma (OR 0.99, 95%CI 0.98-1.00).
      CONCLUSION: Improving the general awareness of the effectiveness of anti
      tuberculosis treatment will help to diminish TB courtesy stigma, and should be
      prioritised over expanding knowledge of mode of transmission. Efforts to reduce
      HIV and TB stigma may increase care seeking for childhood TB symptoms.

PMID- 29025487
TI  - Incorporating social justice and stigma in cost-effectiveness analysis: drug
      resistant tuberculosis treatment.
AB  - Novel therapies for multidrug-resistant tuberculosis (MDR-TB) are likely to be
      expensive. The cost of novel drugs (e.g., bedaquiline, delamanid) may be so
      prohibitively high that a traditional cost-effectiveness analysis (CEA) would
      rate regimens containing these drugs as not cost-effective. Traditional CEA may
      not appropriately account for considerations of social justice, and may put the
      most disadvantaged populations at greater risk. Using the example of novel drug
      regimens for MDR-TB, we propose a novel methodology, 'justice-enhanced CEA', and
      demonstrate how such an approach can simultaneously assess social justice impacts
      alongside traditional cost-effectiveness ratios. Justice-enhanced CEA, as we
      envision it, is performed in three steps: 1) systematic data collection about
      patients' lived experiences, 2) use of empirical findings to inform social
      justice assessments, and 3) incorporation of data-informed social justice
      assessments into a decision analytic framework that includes traditional CEA.
      These components are organized around a core framework of social justice
      developed by Bailey et al. to compare impacts on disadvantage not otherwise
      captured by CEA. Formal social justice assessments can produce three composite
      levels: 'expected not to worsen...', 'may worsen...', and 'expected to worsen
      clustering of disadvantage'. Levels of social justice impact would be assessed
      for each major type of outcome under each policy scenario compared. Social
      justice assessments are then overlaid side-by-side with cost-effectiveness
      assessments corresponding to each branch pathway on the decision tree. In
      conclusion, we present a 'justice-enhanced' framework that enables the
      incorporation of social justice concerns into traditional CEA for the evaluation
      of new regimens for MDR-TB.

PMID- 29025488
TI  - Stigma as a barrier to the use of occupational health units for tuberculosis
      services in South Africa.
AB  - SETTING: Tuberculosis (TB) is the leading cause of death in South Africa, and
      health care workers (HCWs) are disproportionally affected. The resulting
      absenteeism strains the already overburdened health system. Although hospital
      occupational health care units (OHUs) are cost-effective and of crucial
      importance in tackling the TB epidemic, the fear of being stigmatised by other
      colleagues might lead HCWs to avoid using OHUs. OBJECTIVE: To investigate whether
      the perception of TB stigma among colleagues has a negative effect on the
      willingness to use OHUs for TB services. DESIGN: In the Free State Province,
      South Africa, a representative sample of 804 HCWs from six hospitals were
      surveyed on workplace stigma as a predictor for the use of OHUs for TB services.
      Applying structural equation modelling, we also controlled for exogenous
      variables. RESULTS: There was a significant negative relationship between the
      perception of stigmatising attitudes and behaviours among co-workers and the use
      of OHUs for TB screening (beta -0.21, P = 0.000), treatment (beta -0.16, P =
      0.001) and isoniazid preventive therapy (beta -0.17, P = 0.000). CONCLUSION: The
      negative effect of TB stigma on OHU use among HCWs can impact upon their health
      and increase hospital costs. This needs to be addressed by interventions
      combating TB stigma among HCWs in the workplace.

PMID- 29025489
TI  - Evidence-based interventions to reduce tuberculosis stigma: a systematic review.
AB  - SETTING: While substantial progress is being made in tuberculosis (TB) control,
      the success of public health efforts is hampered by pervasive stigma. OBJECTIVE:
      To perform a systematic literature review to assess the effectiveness of
      interventions aimed at reducing TB stigma in patients, health care workers, care
      givers and the general community. DESIGN: Studies were eligible for inclusion if
      they evaluated interventions aimed at reducing TB stigma and were published
      between 1950 and 2015. We searched eight databases (PubMed, Cochrane Library,
      Ovid, Embase, PsycInfo, Sociological Abstracts, Cumulative Index to Nursing and
      Allied Health Literature, World Health Organization Latin American and Caribbean
      Health Sciences Literature), and complemented the searches by using the snowball
      strategy and by reviewing relevant grey literature. RESULTS: Only seven studies
      were identified as providing quantitative (n = 4) or qualitative (n = 3) evidence
      of effectiveness in reducing TB stigma. Quality assessment of the studies was
      poor. Knowledge-shaping and attitude-changing interventions aimed at the public,
      patients and their families were effective in reducing anticipated stigma. Home
      visits and support groups were effective in reducing both anticipated and
      internalised stigma. CONCLUSION: There is a dearth of reliable information on the
      effectiveness of TB stigma-reduction interventions. Knowledge-shaping, attitude
      changing and patient-support interventions can be effective in reducing TB
      stigma, but more rigorous evaluations are needed.

PMID- 29025491
TI  - Review of postoperative care for Samter's triad patients undergoing endoscopic
      sinus surgery: A double-blinded, randomized controlled trial.

PMID- 29025492
TI  - Esthesioneuroblastoma: The Princess Margaret Hospital experience.

PMID- 29025493
TI  - Addendum.

PMID- 29025490
TI  - Defining the research agenda to measure and reduce tuberculosis stigmas.
AB  - Crucial to finding and treating the 4 million tuberculosis (TB) patients
      currently missed by national TB programmes, TB stigma is receiving well-deserved
      and long-delayed attention at the global level. However, the ability to measure
      and evaluate the success of TB stigma-reduction efforts is limited by the need
      for additional tools. At a 2016 TB stigma-measurement meeting held in The Hague,
      The Netherlands, stigma experts discussed and proposed a research agenda around
      four themes: 1) drivers: what are the main drivers and domains of TB stigma(s)?;
      2) consequences: how consequential are TB stigmas and how are negative impacts
      most felt?; 3) burden: what is the global prevalence and distribution of TB
      stigma(s) and what explains any variation? 4): intervention: what can be done to
      reduce the extent and impact of TB stigma(s)? Each theme was further subdivided
      into research topics to be addressed to move the agenda forward. These include
      greater clarity on what causes TB stigmas to emerge and thrive, the difficulty of
      measuring the complexity of stigma, and the improbability of a universal stigma
      'cure'. Nevertheless, these challenges should not hinder investments in the
      measurement and reduction of TB stigma. We believe it is time to focus on how,
      and not whether, the global community should measure and reduce TB stigma.

PMID- 29025494
TI  - Erratum: Sonography versus plain x rays in diagnosis of nasal fractures.

PMID- 29025495
TI  - Effectiveness of Social Media-based Interventions on Weight-related Behaviors and
      Body Weight Status: Review and Meta-analysis.
AB  - OBJECTIVES: We reviewed scientific literature regarding the effectiveness of
      social media-based interventions about weight-related behaviors and body weight
      status. METHODS: A keyword search were performed in May 2017 in the Clinical
      Trials.gov, Cochrane Library, PsycINFO, PubMed, and Web of Science databases. We
      conducted a meta-analysis to estimate the pooled effect size of social media
      based interventions on weight-related outcome measures. RESULTS: We identified 22
      interventions from the keyword and reference search, including 12 randomized
      controlled trials, 6 pre-post studies and 3 cohort studies conducted in 9
      countries during 2010-2016. The majority (N = 17) used Facebook, followed by
      Twitter (N = 4) and Instagram (N = 1). Intervention durations averaged 17.8 weeks
      with a mean sample size of 69. The meta-analysis showed that social media-based
      interventions were associated with a statistically significant, but clinically
      modest reduction of body weight by 1.01 kg, body mass index by 0.92 kg/m2, and
      waist circumstance by 2.65 cm, and an increase of daily number of steps taken by
      1530. In the meta-regression there was no doseresponse effect with respect to
      intervention duration. CONCLUSIONS: The boom of social media provides an
      unprecedented opportunity to implement health promotion programs. Future
      interventions should make efforts to improve intervention scalability and
      effectiveness.

PMID- 29025496
TI  - The Perceived Impact of I am Moving, I am Learning on Physical Activity and
      Family Involvement: A Preliminary Investigation.
AB  - OBJECTIVES: The purpose of this study was to determine the perceived impact of I
      am Moving, I am Learning (IMIL) on physical activity (PA) levels, along with
      family and community involvement in a Head Start program in Illinois. METHODS:
      Employing qualitative methods, data were collected via a parent/caregiver survey
      and program staff focus groups in Rock Island, Illinois. RESULTS: IMIL was
      perceived to have made an impact in several areas including knowledge, health
      related behaviors, and supportive school and home environments. A positive impact
      also was reported regarding 6 types of family involvement (parenting,
      communicating, decision making, volunteering, community collaboration, and
      learning at home). CONCLUSIONS: Participants in the study reported that IMIL
      contributed to increased levels of PA and family/community involvement. The
      participants perceived that the use of IMIL helped parents/caregivers and their
      children become healthier, by improving the whole family's activity levels.
      Faculty and staff also reported that there were few barriers related to the
      implementation and sustainability of IMIL use in childcare settings.

PMID- 29025497
TI  - The Prevalence of Violent Behavior among Lebanese University Students:
      Association with Behavioral and Mental Health Factors.
AB  - OBJECTIVES: We estimated the prevalence of 2 key violent behaviors (weapons
      carrying and physical fighting), determined the health risk correlates of violent
      behavior, such as current tobacco smoking, alcohol binge drinking, and having
      multiple sexual partners, and investigated the potential mental health factors
      related to violent behavior among Lebanese university students. METHODS: Using a
      cross-sectional design, data were collected from 450 Lebanese university students
      based on proportionate cluster sampling. Various health and behavioral risk
      factors were considered for the analyses. RESULTS: The overall prevalence of
      weapon carrying and physical fighting was reported at 12.7% and 19.1%,
      respectively. Males reported more violent behavior than females; weapon carrying
      (20.7% vs 5.2%, p < .001), and physical fighting (31.8% vs 7.3%, p < .001).
      Students who engaged in violent behaviors were more likely to have risky health
      behaviors than those who were not involved in violent behaviors. Religiosity had
      a significant protective effect against engaging in physical fighting after
      adjusting for socio-demographic factors. CONCLUSIONS: This study bridges the gap
      in the literature about violent behavior among emerging adults in Lebanon. There
      is a need to monitor weapon carrying by university students especially in a
      volatile setting like Lebanon.

PMID- 29025498
TI  - Survey Development to Assess College Students' Perceptions of the Campus
      Environment.
AB  - OBJECTIVE: We developed and tested a College Environmental Perceptions Survey
      (CEPS) to assess college students' perceptions of the healthfulness of their
      campus. METHODS: CEPS was developed in 3 stages: questionnaire development,
      validity testing, and reliability testing. Questionnaire development was based on
      an extensive literature review and input from an expert panel to establish
      content validity. Face validity was established with the target population using
      cognitive interviews with 100 college students. Concurrent-criterion validity was
      established with in-depth interviews (N = 30) of college students compared to
      surveys completed by the same 30 students. Surveys completed by college students
      from 8 universities (N = 1147) were used to test internal structure (factor
      analysis) and internal consistency (Cronbach's alpha). RESULTS: After development
      and testing, 15 items remained from the original 48 items. A 5-factor solution
      emerged: physical activity (4 items, alpha = .635), water (3 items, alpha =
      .773), vending (2 items, alpha = .680), healthy food (2 items, alpha = .631), and
      policy (2 items, alpha = .573). The mean total score for all universities was
      62.71 (+/-11.16) on a 100-point scale. CONCLUSION: CEPS appears to be a valid and
      reliable tool for assessing college students' perceptions of their health-related
      campus environment.

PMID- 29025499
TI  - Food Melt in Consumer Food Environments in Low-income Urban Neighborhoods.
AB  - OBJECTIVES: We systematically evaluated changes in availability, price, and
      quality of perishable food items from the beginning to the end of the month in
      lowincome, urban neighborhoods. METHODS: The sample included grocery stores or
      supermarkets in Cleveland, Ohio, within neighborhoods with >30% of population
      receiving food assistance. We collected data for 2 sequential months during the
      first and fourth weeks of each month. Two coders evaluated stores, collecting
      measures of availability, price, and quality for 50 items. We examined difference
      in number and proportion of items available at the beginning of the month (BOM)
      to items remaining available at the end of the month (EOM), as well as quality
      and price of those items. RESULTS: Across 48 stores, availability at EOM was
      lower than BOM; as store size increased, reduction in availability (ie, food
      melt) was significantly (p < .01) less pronounced. Overall, items became less
      expensive at the EOM whereas quality remained consistent; we noted no
      statistically significant differences by store type for price or quality.
      CONCLUSIONS: Food melt differentially affects individuals in neighborhoods
      without grocery stores. Findings reveal composition of food environments is
      dynamic rather than static, influencing food-purchasing choices among lowincome
      consumers.

PMID- 29025500
TI  - The Influence of Self-efficacy in Medical Drama Television Programming on
      Behaviors and Emotions that Promote Cervical Cancer Prevention.
AB  - OBJECTIVES: We explored the influences of medical drama viewing on health
      behaviors and emotions, and examined the role of self-efficacy in medical drama
      programming. METHODS: A single-factor, 2-condition experimental design that
      manipulated self-efficacy levels was adopted. A total of 131 female undergraduate
      students who were likely involved with the issues of HPV vaccination and cervical
      cancer participated in this experiment. RESULTS: In line with social cognitive
      theory, the results indicated that participants in the high self-efficacy
      condition showed greater behavioral intention to receive a Pap smear (F (1, 126)
      = 4.38, p < .05, partial eta2 = .03) and the HPV vaccine (F (1, 35) = 4.82, p <
      .05, partial eta2 = .12) and higher levels of hope (F (1, 126) = 12.22, p < .01,
      partial eta2 = .09) than participants in the low self-efficacy condition. In
      addition, hope mediated the relationship between self-efficacy condition and
      behavioral intention to receive a Pap smear (B = .16, SE = .08, 95% CI = [.04,
      .38]). CONCLUSIONS: Findings suggest that inclusion of self-efficacy information
      in entertainment programming may lead to beneficial health outcomes. Medical
      drama programming may act as an effective outlet to affect health behaviors and
      emotions of the larger public, ultimately enhancing public health.

PMID- 29025501
TI  - Promoting the Well-being of Urban Youth through Drama-based Peer Education.
AB  - OBJECTIVES: The aim of this study was to examine youths' perceptions of a drama
      based peer education approach to promote adolescent well-being. METHODS: High
      school students facilitated workshops on one of 7 topics (eg, dating violence)
      for 4733 urban elementary, middle, and high school students. Audience members'
      perceptions of workshop content and implementation were examined. RESULTS:
      Analyses suggest that the peer-led workshops addressed important problems for
      youth in the community, were an effective way to deliver information about the
      topics to children and teens, and helped audience members to learn more about the
      topics and how to make responsible decisions. The study also found that some
      program outcomes differed by sex and age. CONCLUSIONS: Findings suggest that
      school-based peer education that integrates drama arts is a promising approach
      for promoting wellness and reducing exposure to violence among urban youth. In
      addition, findings suggest that we can facilitate positive outcomes to the extent
      that we match program content to the developmental needs of children and
      adolescents. The implications of these findings are discussed in terms of
      advancing research on drama-based peer education interventions for urban youth.

PMID- 29025502
TI  - Who Enrolls in a Quit Smoking Program with Yoga Therapy?
AB  - OBJECTIVES: Yoga may improve stress, affect, and weight control, all of which are
      commonly cited barriers to quitting smoking. However, the importance of these
      concerns may vary by sex, race, ethnicity, and age. We examined smoking-relevant
      characteristics of individuals enrolling in an 8-week randomized controlled trial
      testing yoga as a complementary treatment to standard smoking cessation. METHODS:
      Of 958 callers, 227 were eligible and enrolled. RESULTS: The sample was 55%
      female, 86% non-Hispanic white, with a mean age of 46 years (SD = 12). Males
      smoked more cigarettes/ day than females and had lower motivation to quit
      smoking. Females were more likely to smoke for weight control, social and mood
      related reasons, and had higher expectations for the efficacy of yoga. Age was
      negatively associated with the presence of other smokers in the household, and
      smoking in response to negative moods, and was positively associated with smoking
      rate, and confidence in quitting. CONCLUSIONS: This study demonstrated that both
      males and females were interested in a program offering yoga as a complementary
      therapy for smoking cessation. However, there were both sex and age-related
      differences with respect to smoking-related variables that may suggest a need to
      adapt the intervention for sub-populations.

PMID- 29025503
TI  - E-cigarette Use and Cigarette Smoking Cessation among Texas College Students.
AB  - OBJECTIVES: We examined the relationships between e-cigarette use and subsequent
      cigarette smoking behaviors at 6- and 12-month follow-ups among young adults.
      METHODS: Participants were 18-29 year-old current and former cigarette smokers (N
      = 627) at 24 Texas colleges, participating in a 3-wave study. Multi-level,
      multivariable logistic regression models, accounting for school clustering,
      examined the impact of self-reported use of e-cigarettes on cigarette smoking
      status at 6- and 12-month follow-ups. Two mutually-exclusive groups of e
      cigarette users were examined: those that used for cigarette smoking cessation
      and those that used for reasons other than cessation. Baseline covariates
      included socio-demographics, past quit attempts, nicotine dependence, cigarettes
      per day, and other tobacco use. RESULTS: Use of e-cigarettes for cigarette
      smoking cessation was associated with increased odds of cigarette smoking
      cessation at 6- and 12-month follow-ups, while using e-cigarettes for other
      reasons was not, when adjusting for covariates. CONCLUSIONS: Use of e-cigarettes
      for cigarette smoking cessation may reduce cigarette smoking rates in young adult
      college students. Additional research is needed examining e-cigarettes as a
      complement to evidence-based cessation resources that are associated with
      cigarette smoking cessation among young adults.

PMID- 29025504
TI  - Distress Tolerance Links Sleep Problems with Stress and Health in Homeless.
AB  - OBJECTIVE: We examined associations between sleep problems, distress intolerance,
      and perceived stress and health in a convenience sample of homeless adults.
      METHODS: Participants (N = 513, 36% women, Mage = 44.5 +/-11.9) self-reported
      sleep adequacy, sleep duration, unintentional sleep during the daytime, distress
      tolerance, urban stress, and days of poor mental health and days of poor physical
      health over the last month. The indirect effects of sleep problems on stress and
      health through distress tolerance were examined using a non-parametric, bias
      corrected bootstrapping procedure. RESULTS: Sleep problems were prevalent (eg,
      13.0 +/-11.4 days of inadequate sleep and 4.7 +/-7.9 days of unintentionally
      falling asleep during the preceding month). Distress intolerance partially
      accounted for the associations of inadequate sleep and unintentionally falling
      asleep, but not sleep duration, with urban stress and more days of poor mental
      and physical health. CONCLUSIONS: Many homeless individuals endure sleep
      problems. Given the connections between sleep and morbidity and mortality,
      results further support the need for more attention directed toward facilitating
      improvements in sleep quality to improve the quality of life of homeless adults,
      potentially including attention to improving distress tolerance skills.

PMID- 29025505
TI  - Household Food Security Discordance Among Latino Adolescents and Parents.
AB  - OBJECTIVES: We determined the degree of parent-adolescent concordance in reported
      household food security, and delineated variation in concordance as a function of
      selected household and parent-adolescent relationship characteristics. METHODS:
      Cross-tabulations and Cohen's Kappa determined concordance. Multinomial logistic
      regressions delineated variation in concordance as a function of selected
      household and parent-adolescent relationship characteristics for Latino parent
      and adolescent dyads (N = 70). RESULTS: Nearly half the households had concordant
      reports of household food security, but 34% were "discordant" such that parents
      reported food insecurity but adolescents did not, and 17% were "discordant"
      wherein adolescents reported food insecurity but parents did not. Elevated parent
      adolescent conflict was associated with greater odds of discordance wherein
      adolescent reported food insecurity but parent did not. Households with female
      adolescents and income >= $30,000/year were associated with lower odds of
      discordance wherein parent reported food insecurity but adolescent did not.
      CONCLUSIONS: Discordant reports of Latino household food security suggest the
      burden of unequal access to sufficient foods may be underestimated. Discordant
      reports may follow from cultural values that may encourage adolescents to keep
      hunger from their parents.

PMID- 29025506
TI  - Maintenance of Lifestyle Changes at 12-month Follow-up in a Nutrition and
      Physical Activity Trial for Cancer Survivors.
AB  - OBJECTIVES: In this paper, we report maintenance of behavior change in a
      nutrition and physical activity intervention for cancer survivors at 12-months
      follow-up. METHODS: The ENRICH (Exercise and Nutrition Routine Improving Cancer
      Health) program was an 8-week face-to-face program for cancer survivors and
      caregivers, focused on healthy eating, healthy weight, resistance training, and a
      walking program. Randomized controlled trial participants completed a survey and
      7-days of pedometry at baseline, 8-weeks, and 20-weeks. Intervention participants
      completed 12-month measures. Maintenance was assessed by examining change between
      20-weeks and 12-months for cancer survivors. RESULTS: Sixty cancer survivors in
      the intervention group completed baseline data collection, and 29 (48%) completed
      12-month assessments. Initial improvements in step counts, weight, and body mass
      index were maintained from 20-weeks to 12-months. Vegetable consumption declined
      significantly (difference -30g/day; p = .04). Moderate-to-vigorous physical
      activity increased significantly (difference 55 minutes/week; p = .05).
      CONCLUSIONS: Physical activity and weight improvements were maintained over 12
      months indicating the potential for a multiple health behavior intervention to
      help cancer survivors sustain improvements to lifestyle behaviors. Additional
      support is warranted to assist cancer survivors to make and maintain dietary
      changes.

PMID- 29025507
TI  - Development and Validation of the Outcome Expectations for Yoga Scale.
AB  - OBJECTIVE: Our objective was to develop an instrument that can measure outcome
      expectations of yoga and to evaluate the instrument for internal consistency and
      initial construct validity. METHODS: A 20-item scale was developed to assess
      physical, mental, and spiritual health benefits related to yoga practice among
      adults. The scale was tested in a baseline survey with adults participating in a
      clinical trial. Principal component analysis was used to investigate the internal
      structure of the measure. Outcome expectations for yoga were examined for
      demographic differences. RESULTS: The sample (N = 185) was 54% women, 89% white
      and had a mean age of 46 years. The final 20-item scale had high item loadings
      that ranged from .57 to .88 with a Cronbach's alpha value of .96. Significant
      differences were found in outcome expectation score by sex. CONCLUSION: This
      newly developed scale can be used to assess outcome expectations for yoga and
      tailor interventions to promote adherence to yoga practice.

PMID- 29025510
TI  - Editorial.

PMID- 29025508
TI  - Discrepancy in Motivation for Weight Loss and Exercise in Rural Patients.
AB  - OBJECTIVES: We explored the extent to which discrepancy between motivation for
      weight loss and exercise is related to obesity among rural patients with chronic
      disease, and identified the psychosocial correlates of this discrepancy. METHODS:
      497 patients with diabetes and/or hypertension were recruited from a network of
      Federally Qualified Health Centers in the rural South and completed a battery of
      assessments. RESULTS: Most persons in the sample (83.1%) were overweight and
      65.0% were obese. For motivation for change, 70.8% reported being in the Action
      stage or higher for weight loss, whereas only 24.9% reported being in the Action
      stage or higher for motivation for exercise. When controlling for age, education
      level, income, sex, and race/ethnicity, individuals who were motivated for weight
      loss but not exercise were twice as likely to be obese (p = .005). Race and sex
      were significantly associated with this discrepancy, with African-American
      patients 1.7 times as likely (p = .05) and women 2.3 times as likely to be
      discrepant (p = .001). CONCLUSIONS: Findings underscore the importance of
      focusing not simply on weight loss among rural patients with chronic disease, but
      rather to incorporate specific activities designed to build simultaneous
      motivation for engaging in exercise.

PMID- 29025511
TI  - Development and Validation of the Perception of Self-Monitoring of Blood Glucose
      Scale in Insulin-Treated Patients With Diabetes.
AB  - BACKGROUND AND PURPOSE: The Perception of Self-Monitoring of Blood Glucose (P
      SMBG) scale was developed and validated to assess perceptions of self-monitoring
      of blood glucose (SMBG) in insulin-treated patients with diabetes. METHOD: An
      initial 68-item version of the P-SMBG has been evaluated by a panel of
      professionals and patients. A sample of 375 patients tested the revised scale.
      RESULTS: Factor analysis suggested a 19-item scale and a 2-factor structure,
      separating negatively and positively worded items. Cronbach's alpha was .84 and
      .72, and the intraclass correlation coefficient was .66 and .57, respectively for
      both factors. Item-total correlations were in the range of .23-.66.
      Convergent/divergent validity was confirmed for the negatively worded items.
      CONCLUSIONS: The final P-SMBG scale (21 items) can be used to assess positive and
      negative perceptions of SMBG in insulin-treated patients with diabetes.

PMID- 29025509
TI  - Clinic Appointment Attendance in Adults with Serious Mental Illness and Diabetes.
AB  - OBJECTIVES: We assessed characteristics that may predict outpatient appointment
      attendance in outpatient medical clinics among patients comorbid for serious
      mental illness (SMI) and type 2 diabetes (DM). METHODS: Baseline covariate data
      from 200 individuals with SMI-DM enrolled in a randomized controlled trial (RCT)
      were used to examine characteristics associated with electronic health record
      identified clinic appointment attendance using a generalized estimating equations
      approach. The analyses evaluated the relationship between clinic attendance and
      potentially modifiable factors including disease knowledge, self-efficacy, social
      support, physical health, and mental health, as well as demographic information.
      RESULTS: Demographic and mental health characteristics were most associated with
      clinic attendance in adults with SMI-DM. Physical health was not associated with
      clinic attendance. CONCLUSIONS: Information on clinical and demographic
      characteristics and factors potentially modifiable by psychological interventions
      may be useful in improving adherence to treatment among SMI-DM patients. It is
      our hope that clinicians and researchers will use these results to help tailor
      adherence-facilitating interventions among people at particular risk for poor
      engagement in care.

PMID- 29025512
TI  - Impact of mitomycin C on the mRNA expression signatures of immunological
      biomarkers in eosinophilic nasal polyposis.
AB  - BACKGROUND: The topical application of mitomycin C has been evaluated as a
      complementary therapy for eosinophilic nasal polyposis (ENP). However, the
      mechanism underlying the additional benefits of mitomycin C for the control of
      eosinophilic inflammation and prevention of posttherapeutic relapse remains to be
      elucidated. In this work, the aim was to characterize the gene expression profile
      by quantitative real-time polymerase chain reaction (qPCR) of proinflammatory and
      regulatory biomarkers that are typically associated with ENP and to assess the
      impact of the topical application of mitomycin C on the nasal mucosal tissue
      immunologic milieu after ENP surgery. METHODS: We have selected 20 patients with
      ENP that were recommended to undergo surgical intervention. Normal mucosal tissue
      was obtained from healthy nasal mucosa from six patients with absence of
      eosinophilic infiltration. To test the effect of mitomycin C, one side of the
      maxillary sinus mucosa was selected for topical application of this drug and the
      other received no further treatment and acted as the control. The genes
      interleukin-4 (IL-4), IL-5, IL-10, IL-13, chemokine (C-C motif) ligand 5 (CCL5),
      CCL24, colony-stimulating factor 2 (CSF2), transforming growth factor beta 1
      (TGFB1), tumor necrosis factor alpha (TNF-alpha), and beta actin (ACTB) were
      selected for gene expression analysis by qPCR. RESULTS: The data showed higher
      expression of proinflammatory biomarkers and lower levels of regulatory TGFB1
      transcripts in ENP mucosal tissue. Surgery with topical application of mitomycin
      C induced a prominent transcriptional down-regulation of the immunologic
      biomarkers, CCL24, TNF-alpha, CSF2, and IL-5, in ENP mucosal tissue.
      Additionally, this treatment restored the levels of chemokines and cytokines to
      those observed in the nasal mucosal tissue of control subjects, except for TGFB1,
      which remained below the reference pattern. Moreover, CSF2 was identified as a
      putative biomarker with significant predictive value for complementary
      prophylactic purposes after surgery in ENP patients. CONCLUSION: After the
      characterization of the expression signatures of immunologic biomarkers in ENP,
      we observed that the topical use of mitomycin C is important for the
      reestablishment of the immunologic microenvironment of a normal expression
      profile of biomarkers involved in ENP mucosal tissue.

PMID- 29025513
TI  - A case-control study of the risk factors associated with sinonasal inverted
      papilloma.
AB  - BACKGROUND: The etiology of sinonasal inverted papilloma (IP) is unknown. This
      study was designed to evaluate the possible risk factors associated with IP
      Methods: This is a case-control epidemiology study in a tertiary referral center.
      Fifty patients with IP and 150 matched controls were interviewed using a
      questionnaire on suspected risk factors. Univariate analysis of the risk factors
      and calculation of the matched odds ratios, the corresponding 95% CIs, and p
      values was performed. Significant risk factors were further studied using
      conditional logistic regression analysis. RESULTS: Outdoor and industrial
      occupations were associated with IP. Tobacco smoking, drinking alcohol, history
      of allergic rhinitis, sinusitis, nasal polyp, non-sinonasal papilloma and non
      sinonasal malignancy were not significant factors. CONCLUSION: Outdoor and
      industrial occupations were associated with IP and may be potential risk factors.
      Future studies are warranted to further evaluate the individual type of
      occupation and chemical involved.

PMID- 29025515
TI  - Regional variations in chronic rhinosinusitis.

PMID- 29025514
TI  - Septal deviation and nasal resistance: An investigation using virtual surgery and
      computational fluid dynamics.
AB  - BACKGROUND: Septal deviation is an extremely common anatomic variation in healthy
      adults. However, there are no standard criteria to determine when a deviated
      septum is clinically relevant. Presently, selection of patients for septoplasty
      is based on mostly clinical examination, which is prone to observer bias and may
      lead to unsuccessful treatment. The objective of this article is twofold. First,
      we investigate whether the location of a septal deviation within the nasal
      passages affects nasal resistance. Second, we test whether computer simulations
      are consistent with rhinomanometry studies in predicting that anterior septal
      deviations increase nasal resistance more than posterior deviations. METHODS: A
      three-dimensional computational model of a healthy nose was created from computed
      tomography scans. Geometry-deforming software was used to produce models with
      septal deviations. Computational fluid dynamics techniques were used to simulate
      nasal airflow and compute nasal resistance. RESULTS: Our results revealed that
      the posterior nasal cavity can accommodate significant septal deviations without
      a substantial increase in airway resistance. In contrast, a deviation in the
      nasal valve region more than doubled nasal resistance. These findings are in good
      agreement with the rhinomanometry literature and with the observation that
      patients with anterior septal deviations benefit the most from septoplasty.
      CONCLUSION: In the model, anterior septal deviations increased nasal resistance
      more than posterior deviations. This suggests, in agreement with the literature,
      that other causes of nasal obstruction (dysfunction of the nasal valve, allergy,
      etc.) should be carefully considered in patients with posterior septal deviations
      because such deviations may not affect nasal resistance. This study illustrates
      how computational modeling and virtual manipulation of the nasal geometry are
      useful to investigate nasal physiology.

PMID- 29025516
TI  - Letter to the Editor.

PMID- 29025518
TI  - Editorial.

PMID- 29025517
TI  - Satisfaction with maxillary sinus surgery might be influenced by risk factors.
AB  - Chronic rhinosinusitis (CRS) is an inflammation of the nose and paranasal sinuses
      lasting for >=12 weeks. Endoscopic sinus surgery (ESS) is considered during
      difficult to treat CRS. The minimally invasive technique focuses on the
      transition areas rather than on the ostia. The aim of this study was to evaluate
      symptoms, the number of acute sinusitis episodes, and satisfaction after ESS with
      either preservation or enlargement of the maxillary sinus ostium. Thirty patients
      with moderate nonpolypous CRS were enrolled. Uncinectomy only and additional
      middle meatal antrostomy were randomized for each side of each patient and
      performed single blindly. The symptoms questionnaires were filled at four time
      intervals. Significant symptom reduction was achieved independently of operation
      technique. The number of acute sinusitis episodes indicating the exacerbation
      rate decreased significantly at 9 and, on average, 68 months postoperatively.
      However, the exacerbation rate began to increase after 9 months postoperatively.
      Three revisions were performed on the side with uncinectomy only and one on the
      side with additional antrostomy. Most patients reported good satisfaction with
      both procedures. There was a trend for patients with asthma and/or job exposure
      to report insignificantly more frequently no satisfaction with surgery,
      especially with the uncinectomy-only procedure. Both procedures seem to be
      efficient in providing symptom relief and satisfaction. More studies are needed
      to evaluate if patients with risk factors benefit more from an ostium-enlarging
      procedure.

PMID- 29025519
TI  - Use of the Rasch Model for Initial Testing of Fit Statistics and Rating Scale
      Diagnosis for a General Anesthesia Satisfaction Questionnaire.
AB  - BACKGROUND AND PURPOSE: The level of patient satisfaction is a result of a
      complex set of interactions between the patient and the health care provider. It
      is important to quantify satisfaction with care because it involves the patient
      in the care experience and decreases the potential gap between expected and
      actual care delivered. METHODS: We tested a preliminary 23-item instrument to
      measure patient satisfaction with general anesthesia care. The rating scale Rasch
      model was chosen as the framework. RESULTS: There were 10 items found to have
      sufficient evidence of stable fit statistics. Items included 2 questions related
      to information provided, 2 questions related to concern and kindness of the
      provider, and 1 question each for interpersonal skills of the provider, attention
      by the provider, feeling safe, well-being, privacy, and overall anesthesia
      satisfaction. CONCLUSION: Such actions as providing enough time to understand the
      anesthesia plan, answering questions related to the anesthetic, showing kindness
      and concern for the patient, displaying good interpersonal skills, providing
      adequate attention to the patient, providing a safe environment that maintains
      privacy and provides a sense of well-being are important actions that are well
      within the control of individual anesthesia providers and may lead to improved
      care from the perception of the patient.

PMID- 29025521
TI  - Restricting indications for sinonasal computed tomography in children with cystic
      fibrosis.

PMID- 29025520
TI  - Validation of the Brazilian Version of the Newcastle Satisfaction With Nursing
      Scales: A Partial Least Squares Path Modeling Approach.
AB  - BACKGROUND AND PURPOSE: Assessing patient satisfaction requires reliable and
      valid instruments. This study evaluated the reliability and validity of the
      Brazilian version of the Newcastle Satisfaction with Nursing Scales (B-NSNS).
      METHODS: This cross-sectional study enrolled 351 adult inpatients. Partial least
      squares path modeling (PLS-PM) approach was used to evaluate the reliability and
      validity of this instrument. RESULTS: After the adjustments of model, both
      constructs exhibited adequate convergent and discriminant validity, showing that
      experiences with nursing care have a significant effect on patient satisfaction
      (r = .70) and account for 49.1% of the variance in patient satisfaction with the
      nursing care (R2 = 0.49). CONCLUSIONS: The B-NSNS result in a valid and reliable
      measure for use in managing nursing care.

PMID- 29025522
TI  - Measuring Maternal Health Literacy in Adolescents Attending Antenatal Care in
      Uganda: Exploring the Dimensionality of the Health Literacy Concept Studying a
      Composite Scale.
AB  - BACKGROUND AND PURPOSE: The purpose of this article is to test the requirement of
      "local independence" in the newly developed "Maternal Health Literacy" (MaHeLi)
      composite scale measuring health literacy in pregnant adolescents attending
      antenatal care. METHODS: The 20-item scale was administered to 384 adolescents
      aged 15-19 years attending antenatal care in Uganda during the period July
      December 2013. Rasch analysis was conducted using RUMM2030. RESULTS: Differential
      item functioning was observed for 3 items. One item had disordered response
      categories. One subscale brought substantial multidimensionality into the MaHeLi
      scale. CONCLUSIONS: Results support the use of a 12-item version of the MaHeLi
      scale. The article shows how Rasch analyses help us to identify violations of
      local independence in scales.

PMID- 29025523
TI  - Construct Validity of the Brazilian Version of the Self-Efficacy for Appropriate
      Medication Adherence Scale.
AB  - BACKGROUND AND PURPOSE: This study aimed to evaluate the reliability and the
      construct validity of the Brazilian version of the Self-Efficacy for Appropriate
      Medication Adherence Scale (SEAMS). METHODS: One hundred forty-seven patients
      with coronary artery disease participated in the study. Reliability was estimated
      by composite reliability (CR). Convergent validity was estimated by the factor
      loading and average variance extracted (AVE). The discriminant validity was
      assessed by cross-factor loadings, comparing the square roots of AVEs by
      correlation coefficients between latent constructs and disattenuated correlation.
      RESULTS: The values of CR of .88 and .99 for Factors 1 and 2, respectively,
      indicate internal consistency reliability. Values of AVE = 0.52 for Factor 1 and
      0.69 for Factor 2 to the convergent validity of the model. Cross-factor loadings
      were found >=.50 for all items of the scale in areas that were allocated in the
      original instrument, square roots of AVEs higher than the correlations between
      the constructs and desatenuada correlation (r = .83), suggesting discriminant
      validity fashion model. CONCLUSION: Confirmatory factor analysis partially
      yielded the construct validity of the Brazilian version of the SEAMS.

PMID- 29025524
TI  - [Neonatal Morbidity and Gestational Diabetes: Coincidence or Consequence of the
      2011 Protocol].
AB  - INTRODUCTION: Gestational diabetes is one of the diseases associated with
      pregnancy with higher rate of complications. Despite being a transitory
      condition, short and long term complications related to gestational diabetes have
      been described. There is scientific evidence to say that good metabolic control
      decreases perinatal complications. In 2011, new criteria was proposed for its
      diagnosis, which made possible its diagnosis during the 1st trimester of
      pregnancy. The aim of this study is to compare neonatal morbidity in two groups
      of women with gestational diabetes diagnosis before and after the latest
      Portuguese guidelines for diabetes and pregnancy were published (February 2011).
      MATERIAL AND METHODS: We included all newborns born in Maternidade Bissaya
      Barreto whose mother, followed at our maternity between 2008 and 2013, had
      unifetal pregnancy complicated by diabetes. We used a perinatal database and
      analysed the impact of the new guidelines in perinatal morbidity over two periods
      of three years. RESULTS: There were 774 women who met the inclusion criteria. We
      found that gestational diabetes was diagnosed earlier, insulin therapy was more
      frequent. Neonatal morbidity was increased, and there were more cases of neonatal
      hypoglycemia and congenital anomalies, and newborns became smaller for
      gestational age. DISCUSSION: The increase in neonatal morbidity was associated
      with early diagnosis and rigorous metabolic control. CONCLUSION: To analyse
      national data will be fundamental to understand this unexpected increase in
      morbidity.

PMID- 29025525
TI  - [Translation and Validation of the FOUR Scale for Children and its Use as Outcome
      Predictor: A Pilot Study].
AB  - INTRODUCTION: The Full Outline of UnResponsiveness - FOUR scale has been
      previously validated to assess impaired consciousness in the adult population.
      The aim of this study is the translation into Portuguese and validation of the
      FOUR scale in the pediatric population. The study also compares the FOUR scale
      and Glasgow coma scale score ratings and the clinical outcome of patients
      hospitalized in Pediatric Intensive Care Units. MATERIAL AND METHODS: This study
      prospectively rated patients admitted to the Pediatric Intensive Care Units with
      impaired consciousness during one year. Both scales were applied daily to
      patients by three types of examiners: intensivists, residents and nurses, from
      the moment of admission until clinical discharge. Neurological sequelae was
      evaluated using the King's Outcome Scale for Childhood Head Injury - KOSCHI.
      RESULTS: Twenty seven patients between one and 17 years of age were included.
      Both scales are reliable and inter-rater reliability was greater for the FOUR
      score. Glasgow coma scale showed a minimum score in eight evaluations, whereas
      the FOUR scale obtained the minimum score in only two of these evaluations. In
      both scales there was a strong association between the admission score and the
      patient's outcome (area under curve FOUR = 0.939, versus Glasgow coma scale =
      0.925). DISCUSSION: The FOUR scale provides more neurological information than
      Glasgow coma scale in patients with impaired consciousness and has prognostic
      interest. CONCLUSION: The FOUR scale can be applied in patients admitted with
      impaired consciousness in Pediatric Intensive Care Units. We think that a
      multicenter study would be very beneficial for confirming and generalizing these
      results.

PMID- 29025526
TI  - Hospital-Acquired Urinary Tract Infections: Results of a Cohort Study Performed
      in an Internal Medicine Department.
AB  - INTRODUCTION: Urinary tract infections are the most frequent healthcare
      associated infections, being related to both high costs and morbidity. Our
      intention was to carry out an epidemiological characterization of hospital
      acquired urinary tract infections that occurred in an internal medicine
      department of a Portuguese hospital. MATERIAL AND METHODS: Retrospective cohort
      study (historic cohort). Data were analysed from a systematic random sample of
      388 patients, representative of the 3492 admissions occurred in 2014 in that
      department. RESULTS: One in four patients underwent the placement of a bladder
      catheter [24.7% (n = 96); 95% CI: 20% - 29%], 36.5% (95% CI: 33% - 48%) of which
      in the absence of clinical criteria for that procedure. The global cumulative
      incidence rate for nosocomial urinary tract infections was 4.6% (95% CI: 2.5% -
      6.7%). Most hospital acquired urinary tract infections (61.1%) were related to
      bladder catheter use. We quantified 3.06 infections / 1000 patient-days and 14.5
      infections / 1000 catheter-days. Catheter associated urinary tract infection
      occurred at an early stage of hospitalization. The vast majority of patients
      (66.7%) that developed a catheter associated urinary tract infection were
      subjected to bladder catheter placement at emergency department. Seventy one per
      cent of catheter associated urinary tract infection occurred in patients that
      were subjected to bladder catheter placement without criteria. DISCUSSION: These
      results point to an excessive and inadequate use of urinary catheters,
      highlighting the need for judicious use taking into account the formal clinical
      indications. The incidence of catheter associated urinary tract infection is
      similar to what we found in other studies. Nevertheless we found a very high
      incidence density per catheter-days that may foresee a problem probably related
      to the absence of early withdrawal of the device, and to both bladder catheter
      placement and maintenance practices. A significant part of catheter associated
      urinary tract infection occurred in patients that had the bladder catheter placed
      in the emergency department, before the admission to the internal medicine ward,
      which highlights the need to assess the urinary catheterization practices in
      those departments. CONCLUSION: The high rate of catheter associated urinary tract
      infection that occurred in the absence of bladder placement indication reinforces
      the need to implement prevention strategies that contemplate the reduction of its
      use. Emergency departments should be part of quality improvement projects in this
      area. Causes for the early onset of catheter associated urinary tract infection
      in this cohort should be investigated.

PMID- 29025527
TI  - [Being a Mother After 35 Years: Will it be Different?]
AB  - INTRODUCTION: Advanced maternal age is defined as maternity after 35 years old
      and is associated with more complications during pregnancy and neonatal period as
      well as decreased fertility. This study aims to examine the relationship between
      advanced maternal age and their maternal and fetal consequences, as well as
      maternal perception of the risk of pregnancy after 35 years old. MATERIAL AND
      METHODS: Observational, retrospective and comparative study, between two groups:
      advanced maternal age group (aged >= 35 years) and non-advanced maternal age
      group (age < 35 years), conducted between March and June 2015. Chi-square test
      and Fisher's exact test were used and considered significant if p < 0.05.
      RESULTS: Of the 736 women admitted to the hospital (32.2% with advanced maternal
      age), 306 were included in the study (153 in each group). In the non-advanced
      maternal age group there was a greater number of primiparous women (p < 0.01). In
      the advanced maternal age group, more previous miscarriages were observed (p <
      0.001), as well as a higher use of assisted reproductive techniques (p < 0.01),
      preformed of amniocentesis (p < 0.001) and dystocia, including caesarean sections
      (p < 0.001). No association was found regarding the presence of maternal
      complications in pregnancy, birth defects, need for neonatal resuscitation or
      prematurity. As for the perception of risk in pregnancy, the non-advanced
      maternal age group considered it to be superior (p < 0.05). DISCUSSION: Most
      women of advanced maternal age have term deliveries without complications.
      Neonatal outcomes seem not to have been influenced by the advanced maternal age.
      CONCLUSION: The consequences of an advanced maternal age pregnancy in this sample
      did not have the same clinical expression as described in the literature. In the
      future, advanced maternal age will possibly be considered after age 40.

PMID- 29025529
TI  - [Volume or Value? The Role of the Radiologist in Managing Radiological Exams].
AB  - INTRODUCTION: The purpose of this study was to understand the reasons and
      quantify the number of ultrasounds and computed tomographies that are potentially
      wasted in the hospital emergency in our institution, and the importance that the
      radiologist can have in the management and screening of these exams. MATERIAL AND
      METHODS: It was decided that urgent tests that were pending for more than seven
      days would be the object of analysis as to why they were not performed,
      consulting the electronic medical records. Six causes were used to cancel the
      requests: 'Changing the patient's status', 'Patient's withdrawal, refusal or
      abandonment', 'Patient's death'; 'No criteria or contraindicated', 'Lack of human
      resources' and 'Mistaken request'. RESULTS: In the year 2015 we obtained 1211
      canceled exams, since they were pending more than a week ago. The first four
      causes totaled 602 exams (sum of 283, 94, 41 and 184). The last two, 609 (sum of
      29 and 580). DISCUSSION: It was verified that the 602 exams corresponding to the
      sum of the first four causes reflected a potential waste in clinical tests since
      they were not determinant in the approach of the Emergency episode nor on the
      final destiny of the patient. Under the tip of the iceberg may exist further
      examinations and patients who have not escaped inadequate or unjustified
      examinations. CONCLUSION: The radiologist can better manage the required
      radiological examinations, effectively screening within a multidisciplinary team
      environment, promoting the development and supporting the respect of guidelines,
      and potentially reducing requests through opinions or second opinions.

PMID- 29025528
TI  - [Evaluation of the Function and Quality of Life after Total Hip Arthroplasty by
      Different Approaches].
AB  - INTRODUCTION: To assess the function and quality of life in patients undergoing
      total hip arthroplasty distinguishing two surgical approaches (posterior /
      anterolateral) used by the Orthopedics department of Centro Hospitalar de Leiria.
      MATERIAL AND METHODS: Retrospective study of 94 patients subject to unilateral
      hip replacement surgery, using the 'Hip Osteoarthritis Outcome Score' (HOOS LK
      2.0) questionnaire, the Trendelenburg test and evaluation of muscle strength of
      the hip abductor muscles with dynamometer. Patients were evaluated at six months,
      12 months, 18 months and 24 months after surgery. RESULTS: The study revealed
      that 97.9% patients completed the rehabilitation program. The postoperative
      evolution (six to 24 months) does not appear to have any differences in results
      when comparing both approaches. At six months the patient operated by the
      anterolateral approach showed worse results when compared with the posterior
      approach, in particular in Hip Osteoarthritis Outcome Score pain, in Hip
      Osteoarthritis Outcome Score symptoms and Hip Osteoarthritis Outcome Score
      activities of daily living. After 24 months, no differences between the two
      surgical approaches were found. Of the 94 patients evaluated, the Trendelenburg
      test was positive in 31% of patients of which 81.9% corresponds to patients
      operated by the anterolateral approach. Muscle strength of the abductors of the
      operated hip was clearly lower in the anterolateral approach at six months, 12
      months, and 24 months. DISCUSSION: This study showed that, in the first six
      months after total hip arthroplasty, the patients operated by the posterior
      approach were, according to the HOOS questionnaire, less symptomatic, and
      presented with better quality of life and less impact on activities of daily
      living and in sport and leisure when compared with the patients operated by the
      anterolateral approach. However, these differences were matched over the 24
      months. Moreover, the results of muscle strength of the abductor muscles of the
      hip were clearly superior in patients operated by the posterior approach at six
      months, at 12 months and at 24 months compared to the patients operated by the
      anterolateral approach. CONCLUSION: After 24 months post total hip arthroplasty
      there are no differences between the two approaches with regard to function or
      quality of life. However, the patients operated by the anterolateral approach had
      greater muscle strength deficits and higher percentage of positive Trendelenburg
      test.

PMID- 29025530
TI  - Intensive Follow-Up After Curative Surgery for Colorectal Cancer.
AB  - INTRODUCTION: The purpose of postoperative surveillance programs after curative
      treatment for colorectal cancer is to detect asymptomatic recurrences with the
      premise that an important rate will be eligible for curative resection, improving
      overall survival. We have implemented a surveillance program for patients with
      colorectal cancer, stages II-III, with periodic clinical, carcinoembryonic
      antigen and cancer antigen-19-9 assessment, computed tomography and colonoscopy.
      The aim of this study was to assess the rate of curative treatment of recurrence,
      colorectal cancer mortality and clinical characteristics associated with non
      resectable recurrence. MATERIAL AND METHODS: Open cohort study, single center.
      All patients on the intensive surveillance program between March 2008 and January
      2015 were included. STATISTICS: chi-square, Wilcoxon rank sum test, logistic
      regression, Kaplan-Meier log-rank test (SPSS20(r)). RESULTS: We had a total 404
      patients evaluated; 59.6% male; mean age of 65 +/- 10 years; 50.7% rectal tumor;
      56.2% stage III. The average time of follow-up was 37 months and the recurrence
      rate was 12.9% (n = 52), mostly detected in the first three years (88.4%). The
      pattern of recurrence was associated with the site of the primary tumor (p <
      0.001). Twenty-one patients underwent curative resection. Factors associated with
      non-resectable recurrence were aged >= 70 years (p = 0.022), disease location in
      the colon (p = 0.033) and cancer antigen-19-9-9 elevation (p = 0.024). The
      overall rate of cancer-specific mortality was 2.2% (n = 9). DISCUSSION: The
      association between colon cancer and non-resectable recurrence is explained by
      the higher rate of disseminated disease in these patients. Cancer antigen-19-9
      added no benefit to the surveillance program. CONCLUSION: This intensive real
      world postoperative surveillance program allowed performing curative surgery to
      40.3% of patients with recurrence.

PMID- 29025531
TI  - [Endocrinology in Portugal - Census 2016. Board of the Portuguese College of
      Endocrinology and Nutrition of the Portuguese Medical Association].
AB  - INTRODUCTION: On September 2016, the Board of the College of Endocrinology and
      Nutrition of the Portuguese Medical Association carried out a national survey,
      about all Endocrinology, Diabetes and Metabolism Departments of the public
      hospitals included in the Portuguese National Health Service and a simplified
      version of this survey was sent to all endocrinologists working in Portugal and
      registered with the Portuguese Medical Association. MATERIAL AND METHODS: Data
      related to organizational and human resources were collected, reporting the
      situation by the end of year 2015. The census registered 107 individuals and 27
      Departments. RESULTS: The ratio of endocrinologists-population was 1.4, much
      lower than in the other European countries (varies between 2 to 4), resulting in
      alarming shortages of services in some areas of Portugal and in worse quality
      indicators. DISCUSSION: These data suggest that actions should be taken to
      increase the number of endocrinologists and departments in the country.
      CONCLUSION: In recent years, the number of residents has significantly increased,
      which will make it possible to correct this situation.

PMID- 29025532
TI  - Conflict of Interest Disclosure in a Top-Tier Portuguese Medical Journal.
AB  - INTRODUCTION: Scientific medical publications are considered to be a source of
      unbiased and independent information. Authors are required to disclose
      relationships with the pharmaceutical industry for transparency purposes. The aim
      of this work was to assess conflict of interest disclosure in a Portuguese top
      tier medical journal by comparing authors' self-reported conflicts of interest
      with payments listed in the official database of Portuguese Ministry of Health.
      MATERIAL AND METHODS: All articles published in the Portuguese Journal of
      Cardiology from December 2015 to May 2016 were reviewed. Articles based on
      clinical images, with authors affiliated to foreign institutions, editorials,
      letters to the editor, or submitted before January 1st 2015 were excluded.
      Authors were categorized on concordance between self-reported disclosures and
      payments listed in the database. Authors who authored multiple articles were
      counted as new authors, since each paper offered a new opportunity for financial
      disclosure. RESULTS: Of the 155 authors surveyed, 82 (53%) were in perfect
      concordance with the sunshine database, while 73 authors (47%) had one or more
      undisclosed payments. Undisclosed payments totaled over ? 210 000. Four (17%)
      articles mentioned a conflict of interest, 24 articles (96%) had at least one
      author with undisclosed payments. DISCUSSION: None of the payments listed in the
      database was acknowledged in self-reported conflicts of interest. This might
      indicate that authors do not consider their financial relationships with the
      industry to be relevant. CONCLUSION: The lack of concordance between self
      reported conflicts of interest and payments found in the database raises concerns
      about incomplete disclosure.

PMID- 29025533
TI  - Negative betahCG and Molar Pregnancy: The Hook Effect.
AB  - Molar pregnancy, included in gestational trophoblastic disease, is a benign
      pathology with ability to metastasize, usually occurring with excessively high
      betahCG levels. Clinical scenario is usually a woman in extremes of reproductive
      age presenting with amenorrhoea, pain and vaginal blood loss; signs derived from
      high betahCG levels may be present (hyperthyroidism, hyperemesis). Diagnosis is
      based on a positive pregnancy test - usually a qualitative urinary test. The
      limitation of this test results from its inability to become positive in presence
      of markedly high levels of betahCG, saturating the antigens used - known as the
      'hook effect'. With the widespread use of gynaecological ultrasound cases of
      molar pregnancy have been diagnosed in timely fashion. We describe a case
      referred as a degenerating fibroid, with a negative urinary pregnancy test.
      Transvaginal ultrasound was highly suggestive of molar pregnancy, which was
      confirmed with a quantitative betahCG test, allowing for timely treatment. The
      importance of a high index of suspicion for this pathology is tremendous to avoid
      the devastating consequences of a delayed diagnosis.

PMID- 29025534
TI  - [Endovascular Treatment of a Gastroduodenal Artery Pseudoaneurysm Rupture after a
      Car Accident].
AB  - The authors present a case of a 39-year-old man with alcoholic chronic
      pancreatitis that was admitted in the emergency department after a car accident,
      complaining of abdominal pain and looking pale. The patient was hemodinamically
      unstable, requiring blood transfusions. He underwent computed tomography
      angiogram of the abdomen and pelvis, showing a pseudoaneurysm of the
      gastroduodenal artery and a hemoperitoneum. He was referred to our interventional
      radiology unit and submitted to endovascular treatment, consisting of 'backdoor'
      and 'frontdoor' embolization of the gastroduodenal artery and pseudoaneurysm neck
      with coils, with total exclusion in control angiography. With this case
      description we intend to highlight the rarity of the pseudoaneurysm rupture of
      the gastroduodenal artery and to emphasize the importance of an interventional
      radiology response that had a fundamental role in the endovascular treatment, in
      an emergency context.

PMID- 29025535
TI  - Umbilical Cord Hemangioma with Pseudocyst: An Exceptional Finding.

PMID- 29025536
TI  - Foreign Bodies in Pediatrics: A Case to Say "Hello Kitty".

PMID- 29025538
TI  - Letter to the Editor: Maternally Inherited Diabetes and Deafness is Not Only
      Biorgan but Multiorgan.

PMID- 29025537
TI  - Letter to the Editor: Medication-Overuse Headache is Common in Portuguese
      Migraineurs.

PMID- 29025540
TI  - Anatomy and Physiology of the Pericardium.
AB  - The pericardium consists of a visceral mesothelial monolayer (epicardium) that
      reflects over the great vessels and joins an outer, relatively inelastic fibrous
      parietal layer of organized collagen and elastin fibers, between which is a
      potential space that normally contains up to 50 mL of plasma filtrate. Although
      not essential for life, the pericardium serves important albeit subtle functions
      in the euvolemic healthy individual that become increasingly important in
      hypervolemic states and conditions in which the heart enlarges acutely. The
      pericardial functions can be divided into the mechanical, reflex, membranous,
      metabolic, ligamentous.

PMID- 29025539
TI  - Pericardial Effusion and Compressive Disorders of the Heart: Influence of New
      Technology on Unraveling its Pathophysiology and Hemodynamics.
AB  - Constrictive pericarditis and cardiac tamponade cause severe diastolic
      dysfunction, but do not depress systolic function until the agonal state has been
      reached. Multimodality cardiovascular imaging has brought the nuances of
      pericardial disease to the domain of the practicing cardiologist. This
      introduction is a revised article originally written by the late Dr Shabetai for
      a pericardial diseases textbook which was not published. He was the editor of
      previous Pericardial Diseases issue for Cardiology Clinics in the 1980s, it is
      most appropriate to begin our issue with his insights. The remaining articles
      describe advances in diagnosis and management, focusing on clinically important
      aspects of pericardial diseases.

PMID- 29025541
TI  - Imaging of the Pericardium: A Multimodality Cardiovascular Imaging Update.
AB  - Pericardial diseases represent diverse conditions, ranging from painful
      inflammatory states, such as acute pericarditis, to life-threatening tamponade
      and chronic heart failure due to constrictive pericarditis. Multimodality
      cardiovascular imaging plays important roles in diagnosis and management of
      pericardial conditions. This review provides a clinical update on multimodality
      cardiovascular imaging of the pericardium, incorporating echocardiography,
      multidetector computed tomography, and cardiac magnetic resonance imaging,
      focusing on guiding clinicians about when each cardiac imaging modality should be
      used in each relevant pericardial condition.

PMID- 29025542
TI  - Acute and Recurrent Pericarditis.
AB  - Acute and recurrent pericarditis is the most common pericardial syndrome
      encountered in clinical practice either as an isolated process or as part of a
      systemic disease. The diagnosis is based on clinical evaluation,
      electrocardiogram, and echocardiography. The empiric therapy is based on
      nonsteroidal anti-inflammatory drugs plus colchicine as first choice, resorting
      to corticosteroids for specific indications (eg, systemic inflammatory disease on
      corticosteroids, pregnancy, renal failure, concomitant oral anticoagulants), for
      contraindications or failure of the first-line therapy. The most common
      complication is recurrence, occurring in up to 30% of cases after a first episode
      of pericarditis.

PMID- 29025543
TI  - Pericardial Effusion.
AB  - The normal pericardial sac contains up to 50 mL of fluid, which consists of a
      plasma ultrafiltrate. Anything greater constitutes a pathologic effusion. The
      curvilinear pressure-volume relationship of the pericardial sac dictates
      hemodynamic consequences of a pericardial effusion and is responsible for rapidly
      accumulating fluid that causes cardiac tamponade. A variety of diseases and
      complications cause pericardial effusion. The most common are idiopathic
      pericarditis, cancer, connective tissue disorders, and hemorrhage. Management of
      pericardial effusion is dictated by whether tamponade is present or threatened.
      If it is, urgent/emergent pericardiocentesis is indicated. If not, a systematic
      approach to diagnosis and management should be undertaken.

PMID- 29025544
TI  - Cardiac Tamponade.
AB  - Cardiac tamponade is caused by an abnormal increase in fluid accumulation in the
      pericardial sac, which, by raising intracardiac pressures, impedes normal cardiac
      filling and reduces cardiac output, sometimes dramatically so. This article
      outlines the pathophysiology, clinical features, and treatment of this important
      clinical condition highlighting the important role played by echocardiography in
      diagnosis and management.

PMID- 29025545
TI  - Constrictive Pericarditis.
AB  - Constrictive pericarditis is a potentially treatable cause of diastolic heart
      failure that arises because a diseased, inelastic pericardium restricts
      ventricular diastolic expansion. Affected patients present with heart failure
      with predominant right-sided symptoms and signs. The key to diagnosis is
      identification of the unique hemodynamic properties associated with constriction:
      dissociation of intrathoracic and intracardiac pressures and enhanced ventricular
      interaction. Comprehensive echocardiography with Doppler imaging is useful, but
      invasive hemodynamic assessment and cross-sectional imaging may be required for
      confirmation. Cardiac MRI provides an opportunity to evaluate for pericardial
      inflammation. Most cases of chronic constriction are progressive and life
      limiting, and require surgical pericardiectomy.

PMID- 29025546
TI  - Effusive-Constrictive Pericarditis.
AB  - Effusive-constrictive pericarditis (ECP) corresponds to the coexistence of a
      hemodynamically significant pericardial effusion and decreased pericardial
      compliance. The hallmark of ECP is the persistence of elevated right atrial
      pressure postpericardiocentesis. The prevalence of ECP seems higher in
      tuberculous pericarditis and lower in idiopathic cases. The diagnosis of ECP is
      traditionally based on invasive hemodynamics but the presence of
      echocardiographic features of constrictive pericarditis post-pericardiocentesisis
      can also identify ECP. Data on the prognosis and optimal treatment of ECP are
      still limited. Anti-inflammatory agents should be the first line of treatment.
      Pericardiectomy should be reserved for refractory cases.

PMID- 29025547
TI  - Contemporary Techniques of Pericardiectomy for Pericardial Disease.
AB  - Pericardiectomy is a potentially curative treatment for constrictive
      pericarditis. We use a median sternotomy and believe that adequate resection
      involves removal of the diaphragmatic pericardium and the anterior pericardium.
      Late outcomes depend on severity of right-sided heart failure preoperatively, the
      etiology of constrictive pericarditis, and adequate pericardial resection. Late
      results are excellent in patients with idiopathic disease or those with
      pericarditis secondary to prior cardiac operations. However, survival is reduced
      in those with radiation-induced constrictive pericarditis, primarily owing to
      additional secondary effects of radiation on cardiac valves, epicardial coronary
      arteries, and ventricular myocardium where fibrosis may cause associated
      restrictive cardiomyopathy.

PMID- 29025548
TI  - Percutaneous Therapy in Pericardial Diseases.
AB  - Interventional procedures for pericardial diseases include pericardiocentesis,
      drainage of pericardial effusion, intrapericardial therapy, and percutaneous
      balloon pericardiotomy or percutaneous pericardiostomy. Echocardiographic and
      fluoroscopic guidance have greatly increased safety and feasibility. Several
      devices for pericardiocentesis have been tested (PerDucer, PeriAttacher, visual
      puncture systems, Grasper, Scissors, and Reverse slitter), mainly to facilitate
      access to the pericardium in the absence of effusion for epicardial ablations or
      left atrial appendage ligation. In selected patients with pericardial effusions
      that cannot be managed medically or with prolonged drainage, various medications
      can be applied intrapericardially to prevent further recurrences or induce
      sclerosis of the pericardial space.

PMID- 29025549
TI  - Neoplastic Pericardial Disease.
AB  - Pericardial tumors are rare lesions that include a range of neoplastic conditions
      that may arise within the pericardium or metastasize to involve it secondarily.
      Understanding the spectrum of lesions that are included in the differential
      diagnosis of a pericardial mass-lesion is critical to making timely, accurate
      diagnoses and getting the appropriate therapy should one be necessary. This
      review summarizes the radiologic and pathologic findings of the most commonly
      encountered of these entities.

PMID- 29025550
TI  - Congenital Abnormalities of the Pericardium.
AB  - Congenital abnormalities of the pericardium are a rare group of disorders that
      include congenital absence of the pericardium, pericardial cysts, and
      diverticula. These congenital defects result from alterations in the embryologic
      formation and structure of the pericardium. Although many cases are incidentally
      found, they can present as symptomatic, life-threatening disease. Owing to their
      rarity, many cases are inappropriately diagnosed. Alterations in the embryologic
      formation and structure may result in the formation of these congenital
      abnormalities. We review the presentation, diagnosis, and management of
      congenital absence of the pericardium, pericardial cysts, and diverticula. A
      summary of multimodality imaging features is provided.

PMID- 29025551
TI  - Tuberculous and Infectious Pericarditis.
AB  - Viral pericarditis is the most common cause of acute pericarditis and it is
      typically responsive to aspirin or nonsteroidal anti-inflammatory drugs.
      Tuberculous pericarditis is common in immunocompromised patients or in
      immunocompetent patients in endemic areas. The diagnosis of tuberculous
      pericarditis usually requires a multidisciplinary approach, and presumptive
      treatment should be started for people with suspected infections living in
      endemic areas. Antituberculous treatment along with corticosteroid therapy can
      reduce complications from constrictive pericarditis. Purulent pericarditis is
      fatal if untreated. Bacterial and fungal cultures from pericardial fluid and
      blood are essential to determine the best treatment.

PMID- 29025555
TI  - Prognosis in Myocarditis: Better Late Than (N)ever!

PMID- 29025553
TI  - Prognostic Value of Cardiac Magnetic Resonance Tissue Characterization in Risk
      Stratifying Patients With Suspected Myocarditis.
AB  - BACKGROUND: Diagnosing myocarditis is challenged by nonspecific clinical signs
      and symptoms and low accuracy of endomyocardial biopsy. Cardiac magnetic
      resonance imaging (CMR) provides both cardiac anatomy and tissue characterization
      in this setting, but the prognostic value of this method as a primary assessment
      tool in patients with suspected myocarditis remains limited. OBJECTIVES: This
      study sought to determine cardiac event-free survival of a consecutive cohort
      with suspected myocarditis with regard to CMR findings. METHODS: Six hundred
      seventy patients with suspected myocarditis underwent CMR including late
      gadolinium enhancement (LGE) parameters between 2002 and 2015 and were included
      and followed. We performed multivariable model for major adverse cardiovascular
      events (MACE) and determined the continuous net reclassification improvement by
      LGE markers. RESULTS: At a median follow-up of 4.7 years (interquartile range
      [IQR]: 2.3 to 7.3 years), 98 patients experienced a MACE. Two hundred ninety-four
      (44%) patients showed LGE presence, which was associated with a more than
      doubling risk of MACE (hazard ratio [HR]: 2.22; 95% confidence interval [CI]:
      1.47 to 3.35; p < 0.001). Annualized MACE rates were 4.8% and 2.1% corresponding
      to LGE presence and absence, respectively (p < 0.001). In the multivariable
      model, LGE presence maintained significant association with MACE (HR: 1.72; 95%
      CI: 1.08 to 2.76; p = 0.023). The computed continuous net reclassification
      improvement was 0.39 (95% CI: 0.10 to 0.67) when LGE presence was added to the
      multivariable model for MACE. Regarding location and pattern, septal and midwall
      LGE showed strongest associations with MACE (HR: 2.55; 95% CI: 1.77 to 3.83 and
      HR: 2.39; 95% CI: 1.54 to 3.69, respectively; both p < 0.001). A patchy
      distribution portended to a near 3-fold increased hazard to MACE (HR: 2.93; 95%
      CI: 1.79 to 4.80; p < 0.001). LGE extent (per 10% increase) corresponded to a 79%
      increase in risk of MACE (HR: 1.79; 95% CI: 1.25 to 2.57; p = 0.002). A normal
      CMR study corresponded to low annual MACE and death rates of 0.8% and 0.3%,
      respectively. CONCLUSIONS: CMR tissue characterization provides effective risk
      stratification in patients with suspected myocarditis.

PMID- 29025554
TI  - Cardiac MR With Late Gadolinium Enhancement in Acute Myocarditis With Preserved
      Systolic Function: ITAMY Study.
AB  - BACKGROUND: The prognostic role of cardiac magnetic resonance (CMR) and late
      gadolinium enhancement (LGE) has not been clarified in acute myocarditis (AM)
      with preserved left ventricular (LV) ejection fraction (EF). OBJECTIVES: This
      study sought to evaluate the role of CMR and LGE in the prognosis of AM with
      preserved LVEF. METHODS: This study analyzed data from ITAMY (ITalian multicenter
      study on Acute MYocarditis) and evaluated CMR results from 386 patients (299
      male; mean age 35 +/- 15 years) with AM and preserved LVEF. Clinical follow-up
      was performed for a median of 1,572 days. A clinical combined endpoint of cardiac
      death, appropriate implantable cardioverter-defibrillator firing, resuscitated
      cardiac arrest, and hospitalization for heart failure was used. RESULTS: Among
      the 374 patients with suitable images, LGE involved the subepicardial layer
      inferior and lateral wall in 154 patients (41%; IL group), the midwall layer of
      the anteroseptal wall in 135 patients (36%; AS [anteroseptal] group), and other
      segments in 59 patients (16%; other-LGE group), and it was absent in 26 patients
      (no-LGE group). The AS group had a greater extent of LGE and a higher LV end
      diastolic volume index than other groups, but levels of inflammatory markers were
      lower than in the other groups. Kaplan-Meier curve analysis indicated that the AS
      group had a worse prognosis than the other groups (p < 0.0001). Finally, in
      multivariable analysis, AS LGE was the best independent CMR predictor of the
      combined endpoint (odds ratio: 2.73; 95% confidence interval: 1.2 to 5.9; p =
      0.01). CONCLUSIONS: In patients with AM and preserved LVEF, LGE in the midwall
      layer of the AS myocardial segment is associated with a worse prognosis than
      other patterns of presentation.

PMID- 29025557
TI  - Brugada Syndrome: Lessons in Risk Tolerance, Communication, and Education?

PMID- 29025556
TI  - Patients With Brugada Syndrome and Implanted Cardioverter-Defibrillators: Long
      Term Follow-Up.
AB  - BACKGROUND: Implantable cardioverter-defibrillator (ICD) indications for primary
      prevention in Brugada syndrome (BrS) are still debated. OBJECTIVES: The authors
      investigated the long-term outcome after ICD implantation in a large cohort of
      BrS patients. METHODS: Of a total of 370 patients with BrS in follow-up (age 43
      +/- 14 years; 74% male), 104 patients (28.1%) were treated with ICDs. The authors
      analyzed the long-term incidence of shocks and complications. RESULTS: An ICD was
      implanted for secondary prevention in 10 patients (9.6%) and for primary
      prevention in 94 patients (90.4%). After a follow-up of 9.3 +/- 5.1 years, 21
      patients (20.2%) experienced a total of 81 appropriate shocks (incidence rate 2.2
      per 100 person-years). The rate of appropriate shocks was higher in secondary
      prevention patients (p < 0.01). However, 4 of the 45 asymptomatic patients (8.9%)
      experienced appropriate ICD therapy, all with a spontaneous type 1
      electrocardiogram and inducible ventricular arrhythmias. In the multivariable
      analysis, type 1 electrocardiogram with syncope (hazard ratio: 4.96; 95%
      confidence interval: 1.87 to 13.14; p < 0.01) and secondary prevention indication
      (hazard ratio: 6.85; 95% confidence interval: 2.29 to 20.50; p < 0.01) were
      significant predictors of appropriate therapy. Nine patients (8.7%) experienced
      37 inappropriate shocks (incidence rate 0.9 per 100 person-years). Twenty-one
      patients (20.2%) had other ICD-related complications (incidence rate 1.4 per 100
      person-years). Three patients (2.9%) died (1 electrical storm and 2
      noncardiovascular deaths). CONCLUSIONS: ICD therapy is an effective therapy in
      high-risk patients with BrS. However, it is also associated with a significant
      risk of device-related complications. Special care during ICD implantation,
      adequate device programming, and regular follow-up may allow reducing the number
      of adverse events.

PMID- 29025559
TI  - The Role of Glycated Proteins on Cardiovascular Diabetic Complications: New
      Findings.

PMID- 29025558
TI  - Glycated Apolipoprotein A-IV Induces Atherogenesis in Patients With CAD in Type 2
      Diabetes.
AB  - BACKGROUND: Nonenzymatic glycation of apolipoproteins plays a role in the
      pathogenesis of the vascular complications of diabetes. OBJECTIVES: This study
      investigated whether apolipoprotein (apo) A-IV was glycated in patients with type
      2 diabetes mellitus (T2DM) and whether apoA-IV glycation was related to coronary
      artery disease (CAD). The study also determined the biological effects of
      glycated apoA-IV. METHODS: The authors consecutively enrolled 204 patients with
      T2DM without CAD (Group I), 515 patients with T2DM with CAD (Group II), and 176
      healthy subjects (control group) in this study. ApoA-IV was precipitated from
      ultracentrifugally isolated high-density lipoprotein, and its glycation level was
      determined based on Western blotting densitometry (relative intensity of apoA-IV
      glycation). ApoA-IV NE-(carboxylmethyl) lysine (CML) modification sites were
      identified by mass spectrometry in 37 control subjects, 63 patients in Group I,
      and 138 patients in Group II. Saline or glycated apoA-IV (g-apoA-IV) generated by
      glyoxal culture was injected into apoE-/- mice to evaluate atherogenesis, and was
      also used for the cell experiments. RESULTS: The relative intensity and the
      abundance of apoA-IV glycation were associated with the presence and severity of
      CAD in patients with T2DM (all p < 0.05). The experiments showed that g-apoA-IV
      induced proinflammatory reactions in vitro and promoted atherogenesis in apoE-/-
      mice through the nuclear receptor NR4A3. G-apoA-IV with mutations (K-A) at high
      frequency glycation sites exhibited more weakened proinflammatory and atherogenic
      effects than did g-apoA-IV both in vitro and in vivo. CONCLUSIONS: ApoA-IV
      glycation is associated with CAD severity in patients with T2DM, and g-apoA-IV
      induces atherogenesis through NR4A3 in apoE-/- mice.

PMID- 29025560
TI  - Obesity and Atrial Fibrillation Prevalence, Pathogenesis, and Prognosis: Effects
      of Weight Loss and Exercise.
AB  - Both obesity and atrial fibrillation (AF) are increasing in epidemic proportions,
      and both increase the prevalence of cardiovascular disease events. Obesity has
      adverse effects on cardiovascular hemodynamics and cardiac structure and
      function, and increases the prevalence of AF, partly related to electroanatomic
      remodeling in obese patients. However, numerous studies, including in AF, have
      demonstrated an obesity paradox, where overweight and obese patients with these
      disorders have a better prognosis than do leaner patients with the same degree of
      severity of cardiovascular disease/AF. In this paper, the authors discuss special
      issues regarding AF in obesity, as well as the evidence that despite the presence
      of an obesity paradox, there are benefits of weight loss, physical
      activity/exercise training, and increases in cardiorespiratory fitness on the
      prognosis of obese patients with AF.

PMID- 29025561
TI  - Arterial Thrombus Stability: Does It Matter and Can We Detect It?
AB  - The spontaneous lysis of a coronary thrombus is a natural protective mechanism
      against lasting occlusion and downstream infarction. Thrombus stability is thus a
      direct determinant of clinical outcome. Compared with the extensive study of the
      crucial role of platelets, coagulation, and flow in arterial thrombosis, little
      attention has been paid to factors affecting thrombus stability, despite evidence
      linking impaired spontaneous fibrinolytic activity with acute coronary events. We
      summarize experimental evidence for the importance of thrombus stability and
      highlight the need for physiologically relevant tests to assess spontaneous
      disintegration/fibrinolysis of platelet-rich thrombi under arterial flow
      conditions, review techniques to assess thrombus stability in vitro, and describe
      novel imaging techniques to characterize thrombosis in vivo. Such techniques may
      allow tailoring of pharmacotherapy to potentiate thrombus instability, through
      fragmentation of platelet thrombi and/or enhanced endogenous fibrinolysis, to
      reduce infarct size.

PMID- 29025562
TI  - Low-Dose Ticagrelor Versus Clopidogrel in Patients With Prior Myocardial
      Infarction.

PMID- 29025563
TI  - Prediction of Mid-Term Outcomes in Adult Obstructive Hypertrophic Cardiomyopathy
      After Surgical Ventricular Septum Myectomy.

PMID- 29025564
TI  - Pre-Implant Outcome Predictors in Patients With Refractory Cardiogenic Shock
      Supported With VA-ECMO.

PMID- 29025565
TI  - The Benefit of Cardiac Resynchronization Therapy Is Not Hindered by the Number of
      Comorbidities.

PMID- 29025566
TI  - Reply: The Benefit of Cardiac Resynchronization Therapy Is Not Hindered by the
      Number of Comorbidities.

PMID- 29025567
TI  - Cardioprotective Properties of ANGPTL3 Deficiency.

PMID- 29025568
TI  - Reply: Loss-of-Function Mutations to Estimate Pharmacological ANGPTL3 Inhibition.

PMID- 29025570
TI  - Correction.

PMID- 29025569
TI  - Concerns on the Genetic or Therapeutic Antagonism of ANGPTL3.

PMID- 29025571
TI  - Correction.

PMID- 29025572
TI  - The Nitric Oxide Pathway-A Potential Target for Precision Medicine in Pulmonary
      Arterial Hypertension.

PMID- 29025573
TI  - The Nitric Oxide Pathway in Pulmonary Vascular Disease.
AB  - Nitric oxide is an endogenous pulmonary vasodilator that is synthesized from L
      arginine in pulmonary vascular endothelial cells by nitric oxide synthase and
      diffuses to adjacent vascular smooth muscle cells where it activates soluble
      guanylyl cyclase. This enzyme converts GTP to cGMP which activates cGMP dependent
      protein kinase leading to a series of events that decrease intracellular calcium
      and reduce vascular muscle tone. Nitric oxide is an important mediator of
      pulmonary vascular tone and vascular remodeling. A number of studies suggest that
      the bioavailability of nitric oxide is reduced in patients with pulmonary
      vascular disease and that augmentation of the nitric oxide/cGMP pathway may be an
      effective strategy for treatment. Several medications that target nitric
      oxide/cGMP signaling are now available for the treatment of pulmonary
      hypertension. This review explores the history of nitiric oxide research,
      describes the major NO synthetic and signaling pathways and discusses a variety
      of abnormalities in NO production and metabolism that may contribute to the
      pathophysiology of pulmonary vascular disease. A summary of the clinical use of
      presently available medications that target nitric oxide/cGMP signaling in the
      treatment of pulmonary hypertension is also presented.

PMID- 29025574
TI  - Genetics of NO Deficiency.
AB  - The nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway plays a key
      role in regulating cardiovascular homeostasis, and genetic variants allocated to
      NO-cGMP pathway genes, leading to NO-cGMP deficiency, may influence the
      prevalence or course of cardiovascular disease. NO-cGMP deficiency can be caused
      by nitric oxide synthase substrate deficiency, substrate competition, defects, or
      uncoupling; endogenous inhibitors of nitric oxide synthase; decreased cGMP
      production; or increased cGMP degradation. This review presents evidence
      supporting the role of NO-cGMP deficiency in cardiovascular disease, including
      findings from genetic association studies for particular polymorphisms,
      haplotypes, and racial disparities. NO-cGMP pathway components including
      arginases, guanosine-5'-triphosphate cyclohydrolase 1, nitric oxide synthase,
      dimethylarginine dimethylaminohydrolases, soluble guanylyl cyclase, protein
      kinase G, phosphodiesterase 5, and natriuretic peptides will be discussed.

PMID- 29025575
TI  - Biomarkers in Pulmonary Vascular Disease: Gauging Response to Therapy.
AB  - Biomarkers are increasingly being investigated in the treatment of pulmonary
      vascular disease. In particular, the signaling pathways targeted by therapies for
      pulmonary arterial hypertension provide biomarkers that potentially can be used
      to guide therapy and to assess clinical response as an alternative to invasive
      procedures such as right-sided cardiac catheterization. Moreover, the growing use
      of combination therapy for both the initial and subsequent treatment of pulmonary
      arterial hypertension highlights the need for biomarkers in this treatment
      approach. Currently approved therapies for pulmonary arterial hypertension target
      3 major signaling pathways: the nitric oxide-soluble guanylate cyclase-cyclic
      guanosine monophosphate pathway, the endothelin pathway, and the prostacyclin
      pathway. Although the main biomarker used in practice and evaluated in clinical
      trials is N-terminal pro-brain natriuretic peptide, other putative biomarkers
      include the endogenous nitric oxide (NO) synthase inhibitor asymmetric
      dimethylarginine, NO metabolites including S-nitrosothiols and nitrite, exhaled
      NO, endothelins, cyclic guanosine monophosphate, cyclic adenosine monophosphate,
      and atrial natriuretic peptide. This review describes accessible biomarkers,
      related to the actual molecules targeted by current therapies, for measuring and
      predicting response to the individual pulmonary arterial hypertension treatment
      classes as well as combination therapy.

PMID- 29025577
TI  - Right Ventricle Dysfunction in Cardiomyopathy: To Measure Is to Know.

PMID- 29025576
TI  - The Prevalence, Correlates, and Impact on Cardiac Mortality of Right Ventricular
      Dysfunction in Nonischemic Cardiomyopathy.
AB  - OBJECTIVES: This study sought to determine the prevalence, correlates, and impact
      on cardiac mortality of right ventricular (RV) dysfunction in nonischemic
      cardiomyopathy. BACKGROUND: Current heart failure guidelines place little
      emphasis on RV assessment due to limited available data on determinants of RV
      function, mechanisms leading to its failure, and relation to outcomes. METHODS:
      We prospectively studied 423 patients with cardiac magnetic resonance (CMR). The
      pre-specified study endpoint was cardiac mortality. In 100 patients, right heart
      catheterization was performed as clinically indicated. RESULTS: During a median
      follow-up time of 6.2 years (interquartile range: 2.9 to 7.6 years), 101 patients
      (24%) died of cardiac causes. CMR right ventricular ejection fraction (RVEF) was
      a strong independent predictor of cardiac mortality after adjustment for age,
      heart failure-functional class, blood pressure, heart rate, serum sodium, serum
      creatinine, myocardial scar, and left ventricular ejection fraction (LVEF).
      Patients with the lowest quintile of RVEF had a nearly 5-fold higher cardiac
      mortality risk than did patients with the highest quintile (hazard ratio: 4.68;
      95% confidence interval [CI]: 2.43 to 9.02; p < 0.0001). RVEF was positively
      correlated with LVEF (r = 0.60; p < 0.0001), and inversely correlated with right
      atrial pressure (r = -0.32; p = 0.001), pulmonary artery pressure (r = -0.34; p =
      0.0005), transpulmonary gradient (r = -0.28; p = 0.006) but not with pulmonary
      wedge pressure (r = -0.15; p = 0.13). In multivariable logistic regression
      analysis of CMR, clinical, and hemodynamic data the strongest predictors of right
      ventricular dysfunction were LVEF (odds ratio [OR]: 0.85; 95% CI: 0.78 to 0.92; p
      < 0.0001), transpulmonary gradient (OR: 1.20; 95% CI: 1.09 to 1.32; p = 0.0003),
      and systolic blood pressure (OR: 0.97; 95% CI: 0.94 to 0.99; p = 0.02).
      CONCLUSIONS: CMR assessment of RVEF provides important prognostic information
      independent of established risk factors and LVEF in heart failure patients with
      nonischemic cardiomyopathy. Right ventricular dysfunction is strongly associated
      with both indices of intrinsic myocardial contractility and increased afterload
      from pulmonary vascular dysfunction.

PMID- 29025578
TI  - Full Circle on Pulmonary Flow Dynamics in Pulmonary Arterial Hypertension.

PMID- 29025579
TI  - Abnormal Motion Patterns of the Interventricular Septum.

PMID- 29025580
TI  - The Right Ventricle: Unforgettable With Imaging.

PMID- 29025581
TI  - Clonal chromosomal aberrations in Philadelphia negative cells such as monosomy 7
      and trisomy 8 may persist for years with no impact on the long term outcome in
      patients with chronic myeloid leukemia.
AB  - The appearance of clonal chromosomal aberrations in Philadelphia negative cells
      (CCA/Ph-) during the treatment of chronic myeloid leukemia (CML) was recently
      confirmed. Importance of these findings has not been clearly defined. We present
      data on the time of appearance, persistence, size of the CCA/Ph- clone in terms
      of drugs used and hematological, cytogenetic and molecular response rates. The
      focus was on the peripheral blood cytopenias and myelodysplastic changes in the
      bone marrow microscopic evaluation. In 5 out of 155 (3,2%) CML patients, the
      persistent presence (up to nine years) of CCA/Ph- was found (monosomy 7 and
      trisomy 8 in unrelated clones in two patients treated with tyrosine kinase
      inhibitors; trisomy 8 in two patients on imatinib; trisomy 21 in one patient on
      interferon alfa treatment). Aberrations were present in median 24% Ph- cells in 3
      15 subsequent analyses at different cytogenetic and molecular response time
      points. No evident myelodysplastic changes nor transformation to MDS/AML occurred
      in patients with CCA/Ph-. All the patients achieved major molecular response
      (MMR). It seems that CCA/Ph- presence does not affect the long term outcome in
      patients with chronic myeloid leukemia. Further complex monitoring of the CML
      patients with CCA/Ph- is still needed.

PMID- 29025582
TI  - A novel TRIP11-FLT3 fusion in a patient with a myeloid/lymphoid neoplasm with
      eosinophilia.
AB  - FLT3 fusions are associated with myeloid and lymphoid neoplasms with
      eosinophilia. We describe a patient presenting with clinicopathologic features of
      both chronic eosinophilic leukemia, not otherwise specified (CEL, NOS) and
      systemic mastocytosis (SM). The bone marrow demonstrated a myeloproliferative
      neoplasm with eosinophilia and aggregates of atypical mast cells. Cytogenetic
      analysis revealed a t(13;14)(q12;q32), which was subsequently molecularly
      characterized as a novel TRIP11-FLT3 rearrangement. A KIT D816V mutation was also
      identified. The patient rapidly transformed to T-lymphoblastic leukemia/lymphoma
      and expired shortly after diagnosis. This is the fifth FLT3 fusion gene described
      in the literature; the presence of both myeloid and lymphoid neoplasms implicates
      involvement of an early hematopoietic progenitor by rearranged FLT3. We suggest
      that leukemias and lymphomas with FLT3 fusion genes exhibit similar
      clinicopathologic features to, and should be included in, the WHO category of
      "Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA,
      PDGFRB, or FGFR1, or with PCM1-JAK2."

PMID- 29025583
TI  - A rare case of pediatric lipoma with t(9;12)(p22;q14) and evidence of HMGA2-NFIB
      gene fusion.
AB  - Lipoma is a benign tumor, typically of adulthood, with characteristic cytogenetic
      findings, including rearrangement of 12q13-15; these rearrangements often lead to
      the fusion of the HMGA2 gene at this locus to the transcriptional regulatory
      domain of its fusion partner, resulting in neomorphic activity that presumably
      facilitates the neoplastic process. Herein, we report a rare case of pediatric
      lipoma with t(9;12)(p22;q14) and evidence of HMGA2-NFIB gene fusion in a 9 year
      old boy. This case provides further evidence of the link between NFIB
      rearrangement and early-onset, deep-seated lipomatous tumors.

PMID- 29025584
TI  - Regulatory mechanisms of long noncoding RNAs on gene expression in cancers.
AB  - Long non-coding RNAs (lncRNAs) are a heterogeneous class of RNAs that are non
      protein coding transcripts longer than 200 nucleotides. In this review, we
      introduce the mechanisms by which lncRNAs regulate gene expression in four parts,
      epigenetic regulation (genetic imprinting and chromatin remodeling),
      transcriptional regulation (molecular decoy), post-transcriptional regulation
      (splicing and mRNA decay), and translational regulation. H19, Xist, and others
      are involved in genomic imprinting. HOTAIR and ANRIL function in chromatin
      remodeling. GAS5 is degraded through an RNA decay pathway. NEAT1 and MALAT1
      function not only in the regulation of transcription but also in splicing.

PMID- 29025586
TI  - Prognostic classification of MDS is improved by the inclusion of FISH panel
      testing with conventional cytogenetics.
AB  - Cytogenetics is a critical independent prognostic factor in myelodysplastic
      syndromes (MDS). Conventional cytogenetics (CC) and Fluorescence in situ
      hybridization (FISH) Panel Testing are extensively used for the prognostic
      stratification of MDS, although the FISH test is not yet a bona fide component of
      the International Prognostic Scoring System (IPSS). The present study compares
      the utility of CC and FISH to detect chromosomal anomalies and in prognostic
      categorization. GTG-Banding and FISH Panel Testing specifically for -5/-5q, -7/
      7q, +8 and -20q was performed on whole blood or bone marrow samples from 136
      patients with MDS. Chromosomal anomalies were found in 40 cases by CC, including
      three novel translocations. FISH identified at least one anomaly in 54/136
      (39.7%) cases. More than one anomaly was found in 18/54 (33.3%) cases, therefore,
      overall FISH identified 75 anomalies of which 32 (42.6%) were undetected by CC.
      FISH provided additional information in cases with CC failure and in cases with a
      normal karyotype. Further, in ten cases with an abnormal karyotype, FISH could
      identify additional anomalies, increasing the number of abnormalities per
      patient. Although CC is the gold standard in the cytogenetic profiling of MDS,
      FISH has proven to be an asset in identifying additional abnormalities. The
      number of anomalies per patient can predict the prognosis in MDS and hence, FISH
      contributed towards prognostic re-categorization. The FISH Panel testing should
      be used as an adjunct to CC, irrespective of the adequacy of the number of
      metaphases in CC, as it improves the prognostic classification of MDS.

PMID- 29025585
TI  - Genetic Gastric Cancer Susceptibility in the International Clinical Cancer
      Genomics Community Research Network.
AB  - Few susceptibility genes for gastric cancer have been identified. We sought to
      identify germline susceptibility genes from participants with gastric cancer from
      an international hereditary cancer research network. Adults with gastric cancer
      of any histology, and with a germline DNA sample (n = 51), were retrospectively
      selected. For those without previously identified germline mutations (n = 43),
      sequencing was performed for 706 candidate genes. Twenty pathogenic or likely
      pathogenic variants were identified among 18 participants. Eight of the 18
      participants had previous positive clinical testing, including six with CDH1
      pathogenic or likely pathogenic variants, and two with pathogenic MSH2 and TP53
      variants. Of the remaining 10, six were in BRCA1 DNA damage response pathway
      genes (ATM, ATR, BRCA2, BRIP1, FANCC, TP53), other variants were identified in
      CTNNA1, FLCN, SBDS, and GNAS. Participants identified with pathogenic or likely
      pathogenic variants were younger at gastric cancer diagnosis than those without,
      39.1 versus 48.0 years, and over 50% had a close family member with gastric
      cancer (p-values < 0.0001). In conclusion, many participants were identified with
      mutations in clinically-actionable genes. Age of onset and family history of
      gastric cancer were mutation status predictors. Our findings support multigene
      panels in identifying gastric cancer predisposition.

PMID- 29025587
TI  - Addition of chromosomal microarray and next generation sequencing to FISH and
      classical cytogenetics enhances genomic profiling of myeloid malignancies.
AB  - Comprehensive genetic profiling is increasingly important for the clinical workup
      of hematologic tumors, as specific alterations are now linked to diagnostic
      characterization, prognostic stratification and therapy selection. To
      characterize relevant genetic and genomic alterations in myeloid malignancies
      maximally, we utilized a comprehensive strategy spanning fluorescence in situ
      hybridization (FISH), classical karyotyping, Chromosomal Microarray (CMA) for
      detection of copy number variants (CNVs) and Next generation Sequencing (NGS)
      analysis. In our cohort of 569 patients spanning the myeloid spectrum, NGS and
      CMA testing frequently identified mutations and copy number changes in the
      majority of genes with important clinical associations, such as TP53, TET2,
      RUNX1, SRSF2, APC and ATM. Most importantly, NGS and CMA uncovered medically
      actionable aberrations in 75.6% of cases normal by FISH/cytogenetics testing. NGS
      identified mutations in 65.5% of samples normal by CMA, cytogenetics and FISH,
      whereas CNVs were detected in 10.1% cases that were normal by all other
      methodologies. Finally, FISH or cytogenetics, or both, were abnormal in 14.1% of
      cases where NGS or CMA failed to detect any changes. Multiple mutations and CNVs
      were found to coexist, with potential implications for patient stratification.
      Thus, high throughput genomic tumor profiling through targeted DNA sequencing and
      CNV analysis complements conventional methods and leads to more frequent
      detection of actionable alterations.

PMID- 29025588
TI  - Trisomy 12 assessment by conventional fluorescence in-situ hybridization (FISH),
      FISH in suspension (FISH-IS) and laser scanning cytometry (LSC) in chronic
      lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) has an extremely heterogeneous clinical
      course, and prognostication is based on common genetic abnormalities which are
      detected by standard cytogenetic methods. However, current methods are restricted
      by the low number of cells able to be analyzed, resulting in the potential to
      miss clinically relevant sub-clonal populations of cells. A novel high throughput
      methodology called fluorescence in situ hybridization in suspension (FISH-IS)
      incorporates a flow cytometry-based imaging approach with automated analysis of
      thousands of cells. Here we have demonstrated that the FISH-IS technique is
      applicable to aneuploidy detection in CLL samples for a range of chromosomes
      using appropriate centromere probes. This method is able to accurately
      differentiate between monosomy, disomy and trisomy with a sensitivity of 1% in
      CLL. An analysis comparing conventional FISH, FISH-IS and laser scanning
      cytometry (LSC) is presented.

PMID- 29025589
TI  - Potential circulating miRNA signature for early detection of NSCLC.
AB  - Circulating microRNAs (c-miRNAs) are promising biomarkers for screening, early
      detection and prognosis of cancer. The purpose of this investigation was to
      identify a panel of c-miRNAs in plasma that could contribute to early detection
      of non-small cell lung cancer (NSCLC). We profiled the expression of 44 unique
      plasma miRNAs in training set of 34 NSCLC patients and 20 matched healthy
      individuals by miRCURY LNATM Universal RT microRNA PCR Panel and calculated
      dysregulation fold changes using the 2-DeltaDeltaCt equation. Selected plasma
      miRNAs were then validated by SYBR green q-RT PCR using an independent validation
      set of plasma samples from NSCLC patients (n: 72) and NC (n: 50). In the
      validation set, the receiver operating characteristic (ROC) curves were generated
      for four miRNAs. In the training set, 17 miRNAs were significantly up-regulated
      and nine were down-regulated in the plasma from NSCLC patients versus matched
      normal controls. Four miRNAs (miR-21, miR-328, miR-375 and miR-141) were selected
      for validating their diagnostic value in the testing set. ROC plot analysis
      showed that a high specificity (98%) and sensitivity (82.7%) in miR-141 in
      comparing early NSCLC patient and controls. So among these four plasma miRNAs
      only miR-141 could be promising biomarkers for early detection of NSCLC. In
      addition to, we found a significant positive correlation between stage and miR-21
      expression level (95% CI: 0.687-0.863; p-value < 0.0001). Considering the
      accessibility and stability of circulating miRNAs, plasma miR-141 is a useful
      biomarker early detection of NSCLC as a supplement in future screening studies.

PMID- 29025590
TI  - Identification of pathogenic retrotransposon insertions in cancer predisposition
      genes.
AB  - Cancer risks have been previously reported for some retrotransposon element (RE)
      insertions; however, detection of these insertions is technically challenging and
      very few oncogenic RE insertions have been reported. Here we evaluate RE
      insertions identified during hereditary cancer genetic testing using a
      comprehensive testing strategy. Individuals who had single-syndrome or pan-cancer
      hereditary cancer genetic testing from February 2004 to March 2017 were included.
      RE insertions were identified using Sanger sequencing, Next Generation
      Sequencing, or multiplex quantitative PCR, and further characterized using
      targeted PCR and sequencing analysis. Personal cancer history, ancestry, and
      haplotype were evaluated. A total of 37 unique RE insertions were identified in
      10 genes, affecting 211 individuals. BRCA2 accounted for 45.9% (17/37) of all
      unique RE insertions. Several RE insertions were detected with high frequency in
      populations of conserved ancestry wherein up to 100% of carriers shared a high
      degree of haplotype conservation, suggesting founder effects. Our comprehensive
      testing strategy resulted in a substantial increase in the number of reported
      oncogenic RE insertions, several of which may have possible founder effects.
      Collectively, these data show that the detection of RE insertions is an important
      component of hereditary cancer genetic testing and may be more prevalent than
      previously reported.

PMID- 29025591
TI  - Identification of a novel CSF3R-SPTAN1 fusion gene in an atypical chronic myeloid
      leukemia patient with t(1;9)(p34;q34) by RNA-Seq.
AB  - Membrane-proximal and truncated mutations of colony-stimulating factor 3 receptor
      (CSF3R) are frequently found in chronic neutrophilic leukemia (CNL) and atypical
      chronic myeloid leukemia (aCML). However, rearrangement involving CSF3R in
      hematological neoplasms has not been reported. Here, we report a case of a 21
      year-old female diagnosed as aCML with t(1;9)(p34;q34) who presented a CSF3R
      rearrangement. First, RNA sequencing identified a novel fusion transcript
      involving exon 17 of CSF3R and exon 50 of non-erythrocytic-1-spectrin-alpha
      (SPTAN1). Subsequent reverse transcription-polymerase chain reaction (RT-PCR) and
      bidirectional Sanger sequencing confirmed the in-frame fusion. The breakpoint was
      located at the C-terminus of CSF3R, suggesting a pattern of truncation mutation
      of CSF3R. Unexpectedly, the patient failed to achieve a complete hematological
      response following the SRC kinase inhibitor dasatinib therapy, which has been
      reported to effectively inhibit truncated forms of CSF3R. The patient accepted
      allogeneic hematopoietic stem cell transplantation (HSCT) and currently remains
      in a good state. In conclusion, this report is the first to identify a fusion
      involving CSF3R and SPTAN1 in aCML with t(1;9)(p34;q34).

PMID- 29025593
TI  - Prognostic significance of recurrent additional chromosomal abnormalities in
      adult patients with Philadelphia chromosome-positive acute lymphoblastic
      leukemia.
AB  - In Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL),
      additional chromosomal abnormalities (ACAs) are frequently observed. We
      investigated the cytogenetic characteristics and prognostic significance of ACAs
      in Ph-positive ALL. We reviewed the clinical data and bone marrow cytogenetic
      findings of 122 adult Ph-positive ALL patients. The ACAs were examined for
      partial or whole chromosomal gains or losses, and structural aberrations. The
      overall survival (OS) and disease-free survival (DFS) of patients who received
      hematopoietic cell transplantation were compared between the isolated Ph group
      and ACA group. ACAs were present in 73.0% of all patients. The recurrent ACAs
      were extra Ph (24.7%), 9/9p loss (20.2%), and 7/7p loss (19.1%). Complex
      karyotype was found in 28.1% of patients in the ACA group. Younger patients (19
      30 years) in the ACA group showed the highest frequency of extra Ph (54%)
      compared to other age groups. The OS in the ACA group was significantly shorter
      than in the isolated Ph group. The presence of an extra Ph chromosome or 9/9p
      loss was significantly associated with shorter OS and DFS, whereas 7/7p loss and
      complex karyotype were not associated with poorer prognosis. We suggest that
      subclassification of ACAs could be applied to prognostic investigation of Ph
      positive ALL.

PMID- 29025592
TI  - Significantly mutated genes and regulatory pathways in SCLC-a meta-analysis.
AB  - Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers
      and demands effective targeted therapeutic strategies. In this meta-analysis
      study, we aim to identify significantly mutated genes and regulatory pathways to
      help us better understand the progression of SCLC and to identify potential
      biomarkers. Besides ranking genes based on their mutation frequencies, we sought
      to identify statistically significant mutations in SCLC with the MutSigCV
      software. Our analysis identified several genes with relatively low mutation
      frequency, including PTEN, as highly significant (p < 0.001), suggesting these
      genes may play an important role in the progression of SCLC. Our results also
      indicated mutations in genes involved in the axon guidance pathways likely play
      an important role in SCLC progression. In addition, we observed that the mutation
      rate was significantly higher in samples with RB1 gene mutated when compared to
      samples with wild type RB1, suggesting that RB1 status has significant impact on
      the mutation profile and disease progression in SCLC.

PMID- 29025594
TI  - Gene expression profiling, pathway analysis and subtype classification reveal
      molecular heterogeneity in hepatocellular carcinoma and suggest subtype specific
      therapeutic targets.
AB  - A very low 5-year survival rate among hepatocellular carcinoma (HCC) patients is
      mainly due to lack of early stage diagnosis, distant metastasis and high risk of
      postoperative recurrence. Hence ascertaining novel biomarkers for early diagnosis
      and patient specific therapeutics is crucial and urgent. Here, we have performed
      a comprehensive analysis of the expression data of 423 HCC patients (373 tumors
      and 50 controls) downloaded from The Cancer Genome Atlas (TCGA) followed by
      pathway enrichment by gene ontology annotations, subtype classification and
      overall survival analysis. The differential gene expression analysis using non
      parametric Wilcoxon test revealed a total of 479 up-regulated and 91 down
      regulated genes in HCC compared to controls. The list of top differentially
      expressed genes mainly consists of tumor/cancer associated genes, such as AFP,
      THBS4, LCN2, GPC3, NUF2, etc. The genes over-expressed in HCC were mainly
      associated with cell cycle pathways. In total, 59 kinases associated genes were
      found over-expressed in HCC, including TTK, MELK, BUB1, NEK2, BUB1B, AURKB, PLK1,
      CDK1, PKMYT1, PBK, etc. Overall four distinct HCC subtypes were predicted using
      consensus clustering method. Each subtype was unique in terms of gene expression,
      pathway enrichment and median survival. Conclusively, this study has exposed a
      number of interesting genes which can be exploited in future as potential markers
      of HCC, diagnostic as well as prognostic and subtype classification may guide for
      improved and specific therapy.

PMID- 29025595
TI  - First cloned human immortalized adipose derived mesenchymal stem-cell line with
      chimeric SS18-SSX1 gene (SS-iASC).
AB  - The SS18-SSX chimeric gene is unique to synovial sarcoma. Multiple model systems
      including mouse cell lines expressing SS18-SSX, and genetically engineered mouse
      models of synovial sarcoma have been developed to elucidate the role of the
      chimeric gene in synovial sarcomagenesis. Although several cell lines stably
      expressing human SS18-SSX exist, there is an ongoing need for cell culture models
      enabling researchers to investigate the molecular mechanism of SS18-SSX action in
      a relevant cellular context. Here we report the establishment of a novel SS18
      SSX1-expressing cell line created from immortalized human adipose tissue-derived
      mesenchymal stem cells via lentiviral transduction of the chimeric gene. Our cell
      line, termed SS-iASC, has been characterized by karyotyping and cell line
      identification, and stable expression of SS18-SSX1 has been verified using real
      time PCR (RT-PCR), nested PCR, immunofluorescence, and immunoblotting. Focal
      cytokeratin positivity characteristic of synovial sarcoma but no beta-Catenin,
      Bcl-2 or cyclin D1 expression was observed in SS-iASC. The novel cell line
      expressing SS18-SSX1 on a human adipose-derived stromal cell background is
      expected to be helpful in addressing the question whether the chimeric gene alone
      is sufficient to trigger the formation of synovial sarcoma.

PMID- 29025596
TI  - RANK and EGFR in invasive breast carcinoma.
AB  - Breast cancer is the most common malignancy, affecting one in eight women in
      North America and Europe. The human epidermal growth factor receptor (EGFR)
      protein comprises a major determinant of normal development but also cancer. RANK
      receptor (Receptor Activator of Nuclear factor-kappaB) is a tumor necrosis
      superfamily member and a binding partner for RANKL, which was recently implicated
      in breast cancer initiation, progression and metastasis. Here we provide
      preliminary evidence of a possible interplay between RANK and EGFR signaling in
      breast cancer. TCGA (cancergenome.nih.gov) publicly available data for EGFR and
      TNFRSF11A (RANK) genes from breast cancer patients and breast cancer cell lines
      were retrieved and analyzed. RANK mRNA showed a statistically significant
      positive correlation (p <0.001) with the mRNA and protein expression of EGFR, but
      not with ERBB2/3/4. Further analyses of survival data of a group of breast cancer
      patients (n = 248) from TCGA, revealed an EGFRhi/RANKhi subpopulation that showed
      a statistically significant (p = 0.001) reduced overall survival when compared to
      EGFRlow/RANKlow group of patients. Finally, EGFR and RANK combinatorial in vitro
      analyses revealed a significant upregulation of AKT and ERK signaling after EGF
      stimulation in cell lines and also an increase of breast cancer cell
      invasiveness.

PMID- 29025597
TI  - Upregulation of vascular endothelial growth factor (VEGF), its role in
      progression and prognosis of non-small cell lung carcinoma.
AB  - Elevated VEGF mRNA (-DeltaCT) was significantly associated with adenocarcinoma
      histology (vs squamous) and advanced NSCLC clinical stages in a univariable
      analysis; however, this association did not remain significant in the
      multivariable analysis. Of interest, a Kaplan-Meier analysis showed that NSCLC
      patients with higher VEGF mRNA (-DeltaCT >=10) had a significantly poorer overall
      survival and shorter postoperative relapse time in adenocarcinoma and in stage
      III/IV than those with VEGF mRNA of -DeltaCT <10 (P < 0.001). The multivariable
      analysis confirmed that patients with higher VEGF mRNA levels, as well as with
      adenocarcinoma and advanced stages, were independent predictors of a poorer
      survival. However, only the histology of adenocarcinoma remained a significant
      prognostic factor of a shorter postoperative relapse in the multivariable model.
      Quantity of VEGF mRNA can be used as a prognosis factor to predict shorter
      overall survival in patients with NSCLC.

PMID- 29025598
TI  - Acute myeloid leukemia with t(14;21) involving RUNX1 and SYNE2: A novel favorable
      risk translocation?
AB  - In acute myeloid leukemia (AML), a translocation between chromosomes 8q22 and
      21q22 leads to the RUNX1-RUNXT1 fusion gene which, in the absence of a
      concomitant KIT mutation, generally portends a more favorable prognosis.
      Translocations at 21q22, other than those involving 8q22, are uncommon, and the
      specific prognostic and therapeutic implications are accordingly limited by the
      small number of reported cases. In this report, we describe the case of a 67-year
      old gentleman who presented with AML harboring t(14;21)(q23;q22). Subsequent
      molecular analysis revealed mutations in RUNX1, ASXL1, and SF3B1, with
      translocation breakpoints identified within SYNE2 on chromosome 14 and RUNX1 on
      chromosome 21. The functional consequence of the DNA fusion between SYNE2 and
      RUNX1 is unclear. Nonetheless, despite several adverse risk factors associated
      with this patient's AML, he achieved a long-lasting remission with standard
      chemotherapy alone, potentially suggestive of a novel favorable-risk
      translocation in AML involving 21q22.

PMID- 29025599
TI  - Constitutional mosaicism of a de novo TP53 mutation in a patient with bilateral
      choroid plexus carcinoma.
AB  - Choroid plexus tumors (CPT) constitute 2%-5% of all pediatric brain tumors and
      include high grade choroid plexus carcinoma (CPC). About 40% of CPC patients
      harbor germline TP53 mutations, associated with diminished survival rates.
      However, the number of TP53 carriers might be underestimated due to suboptimal
      ability of Sanger sequencing to identify mosaicism. We describe an 18-month-old
      boy with ultra-rare, bilateral disseminated CPC and negative family history of
      cancer. Next generation sequencing (NGS) revealed constitutional mosaicism of de
      novo TP53 mutation, which was barely detectable by Sanger sequencing. This is the
      first description of a de novo TP53 mutation mosaicism in a patient with CPC. Up
      to now four cases of de novo TP53 mutations in CPC patients have been described
      but none of them were mosaic. Since TP53 mutation mosaicism may have an impact on
      management of patients and predisposition to other cancers, a reliable method of
      identification is important. Our results highlight the utility of high-throughput
      technologies in detection of potentially important genetic markers.

PMID- 29025600
TI  - A novel somatic JAK2 kinase-domain mutation in pediatric acute lymphoblastic
      leukemia with rapid on-treatment development of LOH.
AB  - We report a novel somatic mutation in the kinase domain of JAK2 (R938Q) in a high
      risk pediatric case of B-cell acute lymphoblastic leukemia (ALL). The patient
      developed on-therapy relapse at 12 months, and interestingly, the JAK2 locus
      acquired loss of heterozygosity during treatment resulting in 100% mutation load.
      Furthermore, we show that primary ALL mononuclear cells harboring the JAK2 R938Q
      mutation display reduced sensitivity to the JAK1/2 ATP-competitive inhibitor
      ruxolitinib in vitro, compared to ALL cells that carry a more common JAK2
      pseudokinase domain mutation. Our findings are in line with previous reports that
      demonstrate that mutations within the kinase domain of JAK2 are associated with
      resistance to type I JAK inhibitors. Importantly, given the recent inclusion of
      ruxolitinib in trial protocols for children with JAK pathway alterations, we
      predict that inter-patient genetic variability may result in suboptimal responses
      to JAK inhibitor therapy in a subset of cases. The need for alternate targeted
      and/or combination therapies for patients who display inherent or developed
      resistance to JAK inhibitor therapy will be warranted, and we propose that kinase
      mutants less sensitive to type I JAK inhibitors may present a currently
      unexplored platform for investigation of improved therapies.

PMID- 29025601
TI  - A neoplasm with FIP1L1-PDGFRA fusion presenting as pediatric T-cell lymphoblastic
      leukemia/lymphoma without eosinophilia.
AB  - The 2016 World Health Organization (2016 WHO) classification of hematopoietic
      malignancies classifies neoplasms with a fusion between the FIP1L1 and PDGFRA
      genes in 4q12 into a group called "myeloid and lymphoid neoplasms with
      eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 or with PCM1-JAK2".
      Neoplasms characterized by this fusion are pluripotent stem cell disorders that
      can show both myeloid and lymphoid differentiation. They typically occur in adult
      patients and most are characterized by eosinophilia. We describe identification
      of a FIP1L1-PDGFRA fusion in a 13-year-old boy who presented with T-lymphoblastic
      leukemia/lymphoma without eosinophilia. Detection of FIP1L1-PDGFRA driven
      neoplasms at diagnosis is usually critical for proper treatment, since almost all
      reported cases responded to tyrosine kinase inhibitors. However, our patient's
      leukemia was refractory to standard chemotherapy, and did not show a meaningful
      response to tyrosine kinase inhibitor therapy. Testing for a FIP1L1-PDGFRA
      rearrangement is at present limited to patients with idiopathic
      hypereosinophilia, and we hypothesize that this abnormality may be under
      diagnosed in children with acute leukemias.

PMID- 29025602
TI  - Complex tibial plateau fractures: a retrospective study and proposal of treatment
      algorithm.
AB  - INTRODUCTION: Complex tibial plateau fractures are characterized by compression
      and sinking of one or both the articular surfaces. In this study, we evaluated
      clinical and radiological outcomes in patients with 41.C1,41.C2,41.C3 fractures
      according to AO classification. We also provide a specific therapeutic algorithm
      for each type of fracture. MATERIAL AND METHODS: The study was conducted in 43
      patients who underwent surgical treatment for complex tibial plateau fractures
      and were followed for a minimum of 12 months. Outcome measures included: range of
      motion (ROM) recovery, Short Form 36 Health Survey (SF36), Knee injury and
      Osteoarthritis Outcome Score (KOOS), tibial plateau angle (TPA), and posterior
      angle (PA). RESULTS: Analyses were performed in 38 patients after excluding 5
      cases because of missing imaging evaluations at follow-up. All patients showed
      good quality of life in all areas considered by SF36 and KOOS as well as
      satisfactory recovery of ROM. Average TPA and PA values were 87.9 degrees  and
      0.6 degrees , respectively. DISCUSSION: In complex tibial plateau fractures,
      surgical treatment is instrumental to obtain full restoration of the joint
      surface and fast functional recovery. Results are highly related to the type of
      treatment adopted for different kinds of fracture. In our case series, the best
      results were obtained when 41.C1 fractures were treated with a single plate. In
      41.C2 fractures, clinical and imaging outcomes were independent of the number of
      plates used. In contrast, in 41.C3 fractures, optimal results were achieved with
      double plates. CONCLUSIONS: Based on our findings, as also supported by the
      literature, 41.C1 fractures should be treated with single plate, which reduces
      the surgical time, soft tissue damage and infection risk. On the other hand,
      41.C3 fractures have best outcomes in stability, consolidation and recovery time
      when treated with double plate.

PMID- 29025603
TI  - Triangular block bridge method for surgical treatment of complex proximal humeral
      fractures: theoretical concept, surgical technique and clinical results.
AB  - INTRODUCTION: Criteria for classification, indication and choice of a surgical
      device to treat proximal humeral fractures are still controversial. We report an
      original technique based on a mechanical concept with a structural principle of a
      triangle as a rigid body applied to the humeral head fractures in association
      with other devices. This retrospective study aims to describe in detail the
      surgical technique and results at long time follow up. METHODS AND MATERIAL: We
      analysed two series of 101 patients with proximal humeral fractures (mean age,
      52.9 y; range 19-78 y) treated between 2001 and 2012 reporting the clinical and
      radiological results. In the first series of 23 cases (mean age 51.4 y, range 35
      74 y) we used as support a bone piece taken from allograft or autologous
      tricortical iliac crest and shaped as a triangular pyramid during the operation;
      while in the second series of 78 cases (mean age 53.6 years, range 29-78 years,
      SD 13.5 years) a triangular titanium cage was used in 69 patients while in 9
      allograft or bone substitute was used as augmentation. An analytical
      retrospective study was done to understand the mechanical function of medial
      augmentation composed by a solid body in association with different types of
      synthesis to stabilize properly a proximal humeral fracture. RESULTS: We obtained
      excellent and good results in 83,2% of patients, fair in 12,8% and bad in 4% in
      terms of active anterior elevation, external and internal rotation, pain and
      strength according to Constant and DASH score. CONCLUSION: A medial solid body,
      especially in titanium material and shaped as trapezoidal/pyramidal form used to
      fill the secondary bone loss in complex instable proximal humeral fracture,
      allows an anatomic reduction and stable fixation in association with simple and
      more complex tools and it provides a better biomechanical environment for union
      and maintenance of alignment.

PMID- 29025604
TI  - Double plating for bicolumnar distal humerus fractures in the elderly.
AB  - Distal humerus fractures are uncommon injuries requiring specific clinical and
      radiographic analysis in order to plan the optimal therapeutic strategy. In
      particular, bicolumnar distal humerus fractures (Type A2, A3 and C) are complex
      fractures. In the last years, double plating fixation became the standard
      treatment: this procedure helped surgeons to obtain a stable and anatomical
      fixation and an early mobilization, which is the main outcome for obtaining
      valuable functional results. In this retrospective study, we evaluated the use of
      open bicolumnar 90-90 plating for fixation of acute fragility fractures of the
      distal humerus in elderly patients, using the olecranon osteotomy as surgical
      approach.

PMID- 29025605
TI  - Comparison between Carbon-Peek volar locking plates and titanium volar locking
      plates in the treatment of distal radius fractures.
AB  - INTRODUCTION: Unstable intra articular fractures of distal radius are frequently
      being managed with open reduction and internal fixation. Volar locking plate
      based on polyetheretherketon (PEEK) polymer has developed lately as an
      alternative to conventional metallic devices. The advantage of this kind of
      plates include the lack of metal allergies, radiolucency, low artefacts on MRI or
      imaging scans and the high resistance associated to loading forces. The aim of
      this study was to evaluate the clinical and radiological results using a new
      Carbon-PEEK volar locking plate compared with titanium volar locking plates for
      the treatment of distal radius fractures. METHODS AND MATERIAL: Thirty patients
      were included in this study. They all underwent traumatic intra-articular distal
      radius fractures and were surgically treated with volar locking plates. The
      patients were randomly divided in two groups: In Group A (15 patients) the
      fracture was stabilized with a CarboFix volar locking plate whereas in group B
      (15 patients) with an Acu-Lock Volar Distal Radius Plate. Range of motion (ROM),
      grip strength, Disabilities of the Arm, Shoulder and Hand (DASH) score and X-rays
      were evaluated. The mean follow up was 12 months. RESULTS: Analysis of Wrist ROM
      revealed that there was no statistical significant difference (p > 0.05) in
      regards to extension, flexion, ulnar deviation, radial deviation, supination and
      pronation comparing to the unaffected arm and between Group A and Group B. The
      mean score on the DASH was 15.3 in Group A and 13.2 in Group B (p > 0.05).
      Patients were able to return to their normal activities of daily living at an
      average of 4 weeks post-op in both Groups. Overall, the mean VAS score was 3.6
      There were no statistically significant differences (p > 0.05) on X-Rays
      examination between two Groups in regards to alignment and fracture healing.
      CONCLUSIONS: Volar locking plates represent the most common procedure for the
      treatment of displaced distal radius fractures. In our series Carbon-peek volar
      locking plates seems to be analogue to titanium volar locking plates in terms of
      radiographic parameters and functional outcome.

PMID- 29025606
TI  - Does routine carpal tunnel release during fixation of distal radius fractures
      improve outcomes?
AB  - OBJECTIVE: This case-control study was designed to test the hypothesis whether
      carpal tunnel release (CTR) during fixation of distal radius 23-C2 AO fractures
      improves outcomes. METHODS: Thirty-five consecutive patients who sustained distal
      radius fractures of the dominant hand participated in this study. Patients were
      allocated into two groups: (a) The ORIF + CTR (16 patients (11 males and 5
      females)); (b) the ORIF and NOT CTR 19 patients (12 males and 7 females). Patient
      assessment included visual analogic scale of pain (VAS), the subjective Mayo
      Wrist Score (MWS), electromyograms (EMG) at 3 month and 6 months from the day of
      injury and complications. All patients had the same physiotherapy treatment
      algorithm following surgery. Patient follow up took place at 1 month, 3, 6, and
      12 months. RESULTS: A the T12 month follow up point the VAS average was 0.8
      (range 0-3) in ORIF + CTR group compared to 1.2 (range 0-3) in the ORIF and NOT
      CTR. The MWS average was 98.7 (range 95-100) in ORIF + CTR group versus 97.6
      (range 95-100) in ORIF no CTR group. There was no statistical significance (p >
      0.5) between the two groups during the follow up period. Patients in the sixth
      month of ORIF + CTR had no suffering of the median nerve, while 31.58% of
      patients in ORIF and no CTR found to have carpal tunnel syndrome. CONCLUSIONS:
      Routine release of the transverse carpal ligament at the time of fracture
      fixation may reduce the incidence of postoperative median nerve dysfunction.

PMID- 29025607
TI  - PEEK radiolucent plate for distal radius fractures: multicentre clinical results
      at 12 months follow up.
AB  - INTRODUCTION: Open reduction and internal fixation (ORIF) with plate and screws
      represents the recommended treatment for unstable intra-articular distal radius
      fractures. Although significant progresses in surgical technique have been made,
      anatomical reconstruction of radio-carpal articular surface still represent a
      difficult task, especially in multifragmentary fractures. Available PEEK
      reinforced-carbon fiber composite radiolucent devices allow both an easier and
      more careful assessment of intra-operative reduction of the articular surface of
      distal radius and prompt correction of any residual step deformity. MATERIALS AND
      METHODS: We retrospectively reviewed clinical and radiological multicentre
      results of 71 consecutive AO B and C fracture pattern of distal radius treated
      using the same PEEK reinforced-carbon fiber composite radiolucent plate. RESULTS:
      Three patients lost at final follow up and 4 cases with incomplete radiological
      documentations were excluded from the study. 64 patients (38 females, 26 males)
      were available and formed the basis of this report. Fracture types included 9
      patients with 23-B, 13 patients 23-B2,15 patients with 23-B3,10 patients with 23
      C1, 7 patients with 23-C2 and 10 patients with 23-C3. Mean Modified Mayo wrist
      Score was on average 38.11 (SD 10.1; range 24-75, 95%CI 34.7-41.4), 67.22 (SD
      9.6, range 50-90, 95%CI 64-70.4), 90.54 (SD 6.3, range 75-100, 95%CI 88.4-92.6)
      at one, two and twelve months of follow-up, respectively. A statistically
      significant difference was found between mean scores at different follow-up
      periods (p = 0.001). We noted 1 case of distal screw fixation aseptic loosening
      at 5 months post surgical intervention. CONCLUSIONS: PEEK reinforced-carbon fiber
      composite radiolucent plate represents a useful device for treatment of complex
      distal radius fractures in the adult population. It possesses unique
      biomechanical properties and allows for an easier anatomical reduction during
      surgical intervention.

PMID- 29025608
TI  - Proximal femoral fractures in elderly people: time to surgery. The experience of
      Milan's "ASST Pini/CTO".
AB  - Proximal femoral fractures in elderly patients represent a rapidly increasing
      socio-economic problem. The functional recovery and the mortality rate are
      influenced by a substantial quantity of variables, including the waiting time for
      surgical treatment ("time to surgery"). This study aims at investigating the
      average waiting time, and ascertaining the causes and effects, together with
      other non-modifiable variables, on the outcome for patients admitted to Milan's
      Istituto Ortopedico Gaetano Pini (Gaetano Pini Orthopaedic Institute) with a
      proximal femoral fracture. Data have been collected from 234 patients, between
      May and November 2015. Parameters recorded and analysed included fracture type,
      presence of comorbidities (Charlson Index (CCI)), the ASA (American Society of
      Anesthesiology) score, day of the week presenting to hospital, the type of
      treatment received, the functional recovery, and the patient's condition on
      discharge. In 46.4% of cases, the duration of preoperative stay prior to surgery
      was found to be in line with what is recommended in the literature (<48 h). In
      20% of cases, the time to surgery was found to exceed 96 hours. The data
      collected that pertain to the distribution of the sample and the comorbidities
      were shown to be in line with the literature. A statistical significant
      difference was found between day of the week that the patient was admitted to
      hospital and the waiting time for surgery.

PMID- 29025609
TI  - Blood loss in trochanteric fractures: multivariate analysis comparing dynamic hip
      screw and Gamma nail.
AB  - INTRODUCTION: Anaemia in patients with trochanteric fracture is associated with
      increased morbidity and mortality and it is an independent risk factor for
      functional mobility of patients. Several authors have reported the blood loss
      following operative treatment comparing different fixation systems but few
      authors have evaluated many associated variables that could influence the
      perioperative blood loss. PURPOSE: To evaluate the blood loss in patients that
      had their trochanteric fracture stabilized with dynamic hip screw (DHS) or Gamma
      nail. Multivariate analysis of different variables that can influence blood loss
      was carried out (type of fracture, antiaggregant or anticoagulant therapy, time
      to surgery). The hypothesis was that there is no difference in terms of blood
      loss in patients with trochanteric fracture treated with DHS or Gamma nail
      considering all these variables. MATERIALS & METHODS: Perioperative blood loss
      was evaluated in 417 consecutive patients treated for trochanteric fracture with
      DHS or Gamma nail between January 2010 and March 2013. The perioperative blood
      loss was calculated using the Lisander formula modified by Foss-Kehlet based on
      pre- and post-operative haemoglobin values and transfusion rates. Univariate and
      multivariate analysis were performed integrating the following variables: type of
      fracture (A1 vs A2), antiaggregant/anticoagulant therapy vs no therapy, time to
      surgery (<24 vs >24 hours from trauma), type of implant (DHS vs Gamma nail).
      RESULTS: A significant blood loss (p <0.05) was observed between A1 and A2
      fracture types (1247ml vs 1796.7ml), antiaggregant/anticoagulant therapy and no
      therapy (1592.7ml vs 1470.2ml), time-to-surgery <24 and >24 hours from trauma
      (1584.4ml vs 1323.9ml), DHS and Gamma nail (894.7ml vs 1720.6ml). At multivariate
      analysis, in the A1 fracture groups the DHS showed a significant lower blood loss
      compared to Gamma nail (p < 0.05). CONCLUSIONS: According to the perioperative
      blood loss, DHS should be used in A1 fractures while Gamma nail can be taking in
      account for the unstable A2 fractures.

PMID- 29025610
TI  - Is endoprosthesis safer than internal fixation for metastatic disease of the
      proximal femur? A systematic review.
AB  - INTRODUCTION: Metastases to the proximal femur are usually managed surgically by
      tumor resection and reconstruction with an endoprosthesis, or by fixation with
      osteosynthesis. Still controversy remains regarding the most appropriate surgical
      treatment. We posed the following questions: (1) Is the frequency of surgical
      revision greater in patients treated with internal fixation than endoprosthetic
      reconstruction, and (2) Do complications that do not require surgery occur more
      frequently in patients treated with internal fixation rather than in those with
      endoprosthetic reconstruction? MATERIALS AND METHODS: A systematic review was
      performed of those studies reporting on surgical revision and complication rates
      comparing the two surgical methods. Ten studies including 1107 patients met the
      inclusion criteria, three with high methodological quality, three intermediate,
      and four with lowquality, according to the STROBE guidelines. RESULTS: At
      present, prosthetic dislocation is the most common complication observed in
      patients managed by prosthesis replacement of the proximal femur, while loosening
      was the main cause of reoperation in the fixation group. Time to reintervention
      ranged from 3 to 11.6 months for the prosthetic replacement and from 7.8 to 22.3
      months for the fixation group. Non surgical complications, (mainly dislocations
      and infections) were more commonly observed in patients operated on by prosthetic
      replacement. CONCLUSIONS: Implant related complications and surgery-related
      morbidity should be taken into account in the decision-making process for the
      surgical management of these patients. These data can improve the surgeon-patient
      communication and guide further studies on patients' survival and complications
      with respect to surgery.

PMID- 29025611
TI  - Carbon-fiber reinforced intramedullary nailing in musculoskeletal tumor surgery:
      a national multicentric experience of the Italian Orthopaedic Society (SIOT) Bone
      Metastasis Study Group.
AB  - INTRODUCTION: Carbon fiber reinforced (CFR) implants have been proposed for the
      treatment of fractures or impending fractures of the long bones in the oncology
      patient. Aim of this study is to present the largest cohort of oncology patients
      operated by CFR nailing by the Italian Orthopaedic Society (SIOT) Bone Metastasis
      Study Group. METHODS: 53 adult oncology patients were operated on with a CFR-PEEK
      nail. All the data from adjuvants therapies were collected. Bone callus
      formation, response to radiotherapy, relapse or progression of the osteolysis
      were recorded. Hardware survival and failure, breakage and need for implant
      revision were also analysed. RESULTS: Anatomical implantation of nails include
      humerus (n = 35), femur (n =11) and tibia (n = 7). The most frequent tumors
      affecting the bone were myeloma (n = 13), breast (n = 11), lung (n = 8), and
      renal cell cancer (n = 7). Acrylic cement reinforcement was used in 2 patients.
      One patient was subjected to electrochemotherapy after nail insertion.
      Intraoperative and early postoperative complications occurred in 13.2% and 7.54%
      of patients respectively. Eight patients had local progression and one developed
      a stress fracture proximally to the distal static screw. Radiographic union
      occurred in 14 patients; one screw loosening was recorded. DISCUSSION: There is
      currently a lack of solid evidence on the clinical use of CFR nails in oncologic
      patients. This is the first and largest study of CFR nailing, with the longest
      available follow up. CONCLUSIONS: Implant related complications and surgery
      related morbidity should be taken into account in the decision-making process for
      the surgical management of these patients. These data can improve the surgeon
      patient communication and guide further studies on patients' survival and
      complications with respect to surgery.

PMID- 29025612
TI  - Clavicle aseptic nonunion: is there a place for cortical allogenic strut graft?
AB  - We investigated functional and radiological outcome in 57 cases of midshaft
      clavicle nonunion treated with open reduction and internal fixation with plate
      and screws over a 13 year-period. Intercalary bone graft was used in 42 patients;
      opposite autologous strut graft was used in 31 cases to provide mechanical
      support to the host bone. Patients were analysed using chart and radiological
      review and assessed with DASH questionnaire obtained at the latest follow-up. 37
      patients were male while 20 were females, with a mean age of 35 years (63-17).
      All cases were of nonunion, 35 atrophic and 22 hypertrophic. The dominant side
      was injured in 32 cases and the non dominant in 25 cases. Primarily, 43 cases
      were treated conservatively with a figure of eight bandage. Time between fracture
      and our operative treatment was on average 44 months (13-72 months). Only those
      patients who were symptomatic were included in this study. We used straight
      reconstruction LCP and low profile precontoured plates. By reviewing patients
      charts all the cases but one of nonunion progressed to osseous healing at a mean
      time of 14 weeks (range 12-16). The patient with non-union refused further
      surgery. 49 patients were available for a final follow up. DASH score was 16.7 at
      an average of 42 months. Open surgery and internal fixation, using plate and
      screws in a compression construct is the treatment of choice for symptomatic
      clavicular non-unions. Intercalary autologous or allograft bone graft should be
      used especially in patient with significant bone loss; autologous cortical strut
      graft provides optimum mechanical stability, thus assuring optimal screw purchase
      and allowing immediate limb movement.

PMID- 29025613
TI  - The treatment of long bones nonunions of upper limb with microsurgical cortico
      periosteal free flap.
AB  - BACKGROUND AND PURPOSE: Medial condyle corticoperiosteal flap is an emerging
      option for the treatment of upper limb non-infected nonunions. The hypothesis of
      our study is that corticoperiosteal flap could be an effective and safe procedure
      for the treatment of upper limb non-infected nonunions, evaluating radiographic
      and clinical outcome. METHODS: We enrolled 14 patients who underwent vascularized
      medial femoral condyle corticoperiosteal free flaps from January 2011 to December
      2014. All patients were clinically evaluated (VAS, DASH) before surgery and at 6
      and 12 months post surgery. The radiographic evaluation was performed every 30
      days until the complete healing and at 12-month follow-up. We also recorded the
      range of motion pre and post surgery at the donor site. RESULTS: All nonunion
      sites healed primarily at an average time period of 5.2 months +/-1. Preoperative
      DASH score was 70 +/- 15.6; at 6 month follow-up was 21.51 +/- 10.63; at 12 month
      follow-up 18.0 +/- 9.9. Preoperative VAS was 7.05 +/- 2; at 6-month follow-up was
      2.1 +/- 2; at 12-month follow-up was 1.8 +/- 1.16. Statistical analysis showed a
      significant difference (p <0.001) about the preoperative and the postoperative
      VAS and DASH evaluation both at 6 and 12-month follow-up, but we did not record
      any statistical difference between the 6-month and 12-month follow-up. At the
      donor site, the mean VAS score was 2 +/- 2.1 at seven days post operatively. All
      patients restore the full ROM at 7 days post surgery. CONCLUSIONS: Vascularized
      medial condyle corticoperiosteal free flap represents an effective and safe
      procedure for the treatment of upper limb nonunions.

PMID- 29025614
TI  - Outcome of distal tibia physeal fractures: a review of cases as related to risk
      factors.
AB  - INTRODUCTION: The physeal fractures represent the 20-30% of all fractures of the
      child. The distal tibial physis is the third most frequently injured. The most
      important complication is the premature physeal closure (PPC). Aim of this study
      is to evaluate risk factors that can influence the outcome like fracture pattern,
      fracture displacement, mechanism of injury and treatment method. MATERIAL AND
      METHODS: The records of 46 patients treated for distal tibia physeal fractures
      between 2003 and 2013 were reviewed. Initial injury radiographs were categorized
      according to Salter-Harris and Dias-Tachdjian classifications and the initial and
      post-treatment fracture displacementwas measured. Any complex fractures had
      preoperative CT for additional assessment. Three different types of treatment
      were compared: closed reduction and casting versus closed reduction and
      percutaneous pinning versus ORIF. RESULTS: Therewas significantly less residual
      displacement in patients who had ORIF versus those who had closed reduction and
      percutaneous Kirschner wires or plaster only. In fractures with an intact fibula,
      we found significantly less initial and residual displacement. The Dias-Tachdjian
      classification is significantly correlated with the displacement. Patients
      studied with CT show a less degree of post reduction displacement. At the final
      follow-up we found only one PPC as complication. CONCLUSION: The physeal
      fractures are very common in children and the main goal is to avoid any
      complications. It is clear that the development of complications after distal
      tibial fractures is due to multiple contributing factors like skeletal maturity,
      severity of injury, fracture type, degree of comminution and displacement aswell
      as adequacy of reduction. A premature physeal closure is the most common
      complication. The fibula fracture can play an important role in initial
      displacement. The presence of an intact fibula and a good anatomical reduction
      have a significant positive influence on fracture outcome.

PMID- 29025615
TI  - Treatment of an atrophic clavicle non-union with the chamber induction technique:
      a case report.
AB  - The gold standard technique for treating non-union of the clavicle is based on
      corticocancellous bone graft harvested from the iliac crest and fixation with a
      plate. In cases of large clavicular defects, this surgical procedure becomes
      ineffective and only a complex bone reconstruction can be considered. In the
      herein study we report on a clavicular non-union which was associated with a 4cm
      bone defect that was managed successfully with optimum fixation and the Chamber
      Induction Technique (C.I.T)-formation of the masquelet membrane- and subsequent
      biological augmentation with a composite bone graft.

PMID- 29025616
TI  - The peroneus brevis flap in the treatment of bone infections of the lower limb.
AB  - The Peroneus Brevis Flap is a described option for the soft tissue coverage and
      for small bone gap reconstruction in the lower third of the lower leg, where few
      other local flaps are available and reliable. We analysed retrospectively a case
      series of 11 consecutive patients whose age ranged from 31 to 87 years (mean 56),
      who underwent a reconstruction with a PB flap in the treatment of post-traumatic
      bone infections from October 2010 to February 2012. In our series, only one
      patient at a 3 year minimum follow-up showed recurrence of the bone infection and
      required further surgical treatment. Main complications were partial flap
      necrosis or overlying skin graft necrosis, but without the need of secondary
      surgery. In our experience, the PB flap is a reliable option for soft tissue
      coverage in the treatment of distal leg and ankle osteomyelitis.

PMID- 29025617
TI  - Disaster prevention should be equal.

PMID- 29025618
TI  - Preventing tuberculosis in people with HIV-no more excuses.

PMID- 29025619
TI  - Antenatal multiple micronutrient supplementation: benefits beyond iron-folic acid
      alone.

PMID- 29025620
TI  - Effect of male circumcision on risk of sexually transmitted infections and
      cervical cancer in women.

PMID- 29025621
TI  - Mitigating the financial effects of tuberculosis requires more than expansion of
      services.

PMID- 29025622
TI  - Lessons for the Sustainable Development Goals from Ethiopia's success: the case
      of under-5 mortality.

PMID- 29025623
TI  - A new public health order for Africa's health security.

PMID- 29025624
TI  - Tackling antimicrobial resistance in neonatal sepsis.

PMID- 29025625
TI  - Reframing non-communicable diseases.

PMID- 29025626
TI  - Reframing non-communicable diseases.

PMID- 29025627
TI  - Reframing non-communicable diseases - Authors' reply.

PMID- 29025628
TI  - Beyond divisive dichotomies in disease classification.

PMID- 29025629
TI  - Access, Watch, and Reserve antibiotics in India: challenges for WHO stewardship.

PMID- 29025630
TI  - Correction to Lancet Glob Health 2016; 5: e992-1003.

PMID- 29025632
TI  - Modifiers of the effect of maternal multiple micronutrient supplementation on
      stillbirth, birth outcomes, and infant mortality: a meta-analysis of individual
      patient data from 17 randomised trials in low-income and middle-income countries.
AB  - BACKGROUND: Micronutrient deficiencies are common among women in low-income and
      middle-income countries. Data from randomised trials suggest that maternal
      multiple micronutrient supplementation decreases the risk of low birthweight and
      potentially improves other infant health outcomes. However, heterogeneity across
      studies suggests influence from effect modifiers. We aimed to identify individual
      level modifiers of the effect of multiple micronutrient supplements on
      stillbirth, birth outcomes, and infant mortality in low-income and middle-income
      countries. METHODS: This two-stage meta-analysis of individual patient included
      data from 17 randomised controlled trials done in 14 low-income and middle-income
      countries, which compared multiple micronutrient supplements containing iron
      folic acid versus iron-folic acid alone in 112 953 pregnant women. We generated
      study-specific estimates and pooled subgroup estimates using fixed-effects models
      and assessed heterogeneity between subgroups with the chi2 test for
      heterogeneity. We did sensitivity analyses using random-effects models,
      stratifying by iron-folic acid dose, and exploring individual study effect.
      FINDINGS: Multiple micronutrient supplements containing iron-folic acid provided
      significantly greater reductions in neonatal mortality for female neonates
      compared with male neonates than did iron-folic acid supplementation alone (RR
      0.85, 95% CI 0.75-0.96 vs 1.06, 0.95-1.17; p value for interaction 0.007).
      Multiple micronutrient supplements resulted in greater reductions in low
      birthweight (RR 0.81, 95% CI 0.74-0.89; p value for interaction 0.049), small-for
      gestational-age births (0.92, 0.87-0.97; p=0.03), and 6-month mortality (0.71,
      0.60-0.86; p=0.04) in anaemic pregnant women (haemoglobin <110g/L) as compared
      with non-anaemic pregnant women. Multiple micronutrient supplements also had a
      greater effect on preterm births among underweight pregnant women (BMI <18.5
      kg/m2; RR 0.84, 95% CI 0.78-0.91; p=0.01). Initiation of multiple micronutrient
      supplements before 20 weeks gestation provided greater reductions in preterm
      birth (RR 0.89, 95% CI 0.85-0.93; p=0.03). Generally, the survival and birth
      outcome effects of multiple micronutrient supplementation were greater with high
      adherence (>=95%) to supplementation. Multiple micronutrient supplements did not
      significantly increase the risk of stillbirth or neonatal, 6-month, or infant
      mortality, neither overall or in any of the 26 examined subgroups.
      INTERPRETATION: Antenatal multiple micronutrient supplements improved survival
      for female neonates and provided greater birth-outcome benefits for infants born
      to undernourished and anaemic pregnant women. Early initiation in pregnancy and
      high adherence to multiple micronutrient supplements also provided greater
      overall benefits. Studies should now aim to elucidate the mechanisms accounting
      for differences in the effect of antenatal multiple micronutrient supplements on
      infant health by maternal nutrition status and sex. FUNDING: None.

PMID- 29025633
TI  - Association between male circumcision and women's biomedical health outcomes: a
      systematic review.
AB  - BACKGROUND: Male circumcision reduces men's risk of acquiring HIV and some
      sexually transmitted infections from heterosexual exposure, and is essential for
      HIV prevention in sub-Saharan Africa. Studies have also investigated associations
      between male circumcision and risk of acquisition of HIV and sexually transmitted
      infections in women. We aimed to review all evidence on associations between male
      circumcision and women's health outcomes to benefit women's health programmes.
      METHODS: In this systematic review we searched for peer-reviewed and grey
      literature publications reporting associations between male circumcision and
      women's health outcomes up to April 11, 2016. All biomedical (not psychological
      or social) outcomes in all study types were included. Searches were not
      restricted by year of publication, or to sub-Saharan Africa. Publications without
      primary data and not in English were excluded. We extracted data and assessed
      evidence on each outcome as high, medium, or low consistency on the basis of
      agreement between publications; outcomes found in fewer than three publications
      were indeterminate consistency. FINDINGS: 60 publications were included in our
      assessment. High-consistency evidence was found for five outcomes, with male
      circumcision protecting against cervical cancer, cervical dysplasia, herpes
      simplex virus type 2, chlamydia, and syphilis. Medium-consistency evidence was
      found for male circumcision protecting against human papillomavirus and low-risk
      human papillomavirus. Although the evidence shows a protective association with
      HIV, it was categorised as low consistency, because one trial showed an increased
      risk to female partners of HIV-infected men resuming sex early after male
      circumcision. Seven outcomes including HIV had low-consistency evidence and six
      were indeterminate. INTERPRETATION: Scale-up of male circumcision in sub-Saharan
      Africa has public health implications for several outcomes in women. Evidence
      that female partners are at decreased risk of several diseases is highly
      consistent. Synergies between male circumcision and women's health programmes
      should be explored. FUNDING: US Centers for Disease Control and Prevention and
      Jhpiego.

PMID- 29025634
TI  - Catastrophic costs potentially averted by tuberculosis control in India and South
      Africa: a modelling study.
AB  - BACKGROUND: The economic burden on households affected by tuberculosis through
      costs to patients can be catastrophic. WHO's End TB Strategy recognises and aims
      to eliminate these potentially devastating economic effects. We assessed whether
      aggressive expansion of tuberculosis services might reduce catastrophic costs.
      METHODS: We estimated the reduction in tuberculosis-related catastrophic costs
      with an aggressive expansion of tuberculosis services in India and South Africa
      from 2016 to 2035, in line with the End TB Strategy. Using modelled incidence and
      mortality for tuberculosis and patient-incurred cost estimates, we investigated
      three intervention scenarios: improved treatment of drug-sensitive tuberculosis;
      improved treatment of multidrug-resistant tuberculosis; and expansion of access
      to tuberculosis care through intensified case finding (South Africa only). We
      defined tuberculosis-related catastrophic costs as the sum of direct medical,
      direct non-medical, and indirect costs to patients exceeding 20% of total annual
      household income. Intervention effects were quantified as changes in the number
      of households incurring catastrophic costs and were assessed by quintiles of
      household income. FINDINGS: In India and South Africa, improvements in treatment
      for drug-sensitive and multidrug-resistant tuberculosis could reduce the number
      of households incurring tuberculosis-related catastrophic costs by 6-19%. The
      benefits would be greatest for the poorest households. In South Africa, expanded
      access to care could decrease household tuberculosis-related catastrophic costs
      by 5-20%, but gains would be seen largely after 5-10 years. INTERPRETATION:
      Aggressive expansion of tuberculosis services in India and South Africa could
      lessen, although not eliminate, the catastrophic financial burden on affected
      households. FUNDING: Bill & Melinda Gates Foundation.

PMID- 29025635
TI  - How Ethiopia achieved Millennium Development Goal 4 through multisectoral
      interventions: a Countdown to 2015 case study.
AB  - BACKGROUND: 3 years before the 2015 deadline, Ethiopia achieved Millennium
      Development Goal 4. The under-5 mortality decreased 69%, from 205 deaths per 1000
      livebirths in 1990 to 64 deaths per 1000 livebirths in 2013. To understand the
      underlying factors that contributed to the success in achieving MDG4, Ethiopia
      was selected as a Countdown to 2015 case study. METHODS: We used a set of
      complementary methods to analyse progress in child health in Ethiopia between
      1990 and 2014. We used Demographic Health Surveys to analyse trends in coverage
      and equity of key reproductive, maternal health, and child health indicators.
      Standardised tools developed by the Countdown Health Systems and Policies working
      group were used to understand the timing and content of health and non-health
      policies. We assessed longitudinal trends in health-system investment through a
      financial analysis of National Health Accounts, and we used the Lives Saved Tool
      (LiST) to assess the contribution of interventions towards reducing under-5
      mortality. FINDINGS: The annual rate of reduction in under-5 mortality increased
      from 3.3% in 1990-2005 to 7.8% in 2005-13. The prevalence of stunting decreased
      from 60% in 2000 to 40% in 2014. Overall levels of coverage of reproductive,
      maternal health, and child health indicators remained low, with disparities
      between the lowest and highest wealth quintiles despite improvement in coverage
      for essential health interventions. Coverage of child immunisation increased the
      most (21% of children in 2000 vs 80% of children in 2014), followed by coverage
      of satisfied demand for family planning by women of reproductive age (19% vs
      63%). Provision of antenatal care increased from 10% of women in 2000 to 32% of
      women in 2014, but only 15% of women delivered with a skilled birth attendant by
      2014. A large upturn occurred after 2005, bolstered by a rapid increase in health
      funding that facilitated the accelerated expansion of health infrastructure and
      workforce through an innovative community-based delivery system. The LiST model
      could explain almost 50% of the observed reduction in child mortality between
      2000 and 2011; and changes in nutritional status were responsible for about 50%
      of the 469 000 lives saved between 2000 and 2011. These developments occurred
      within a multisectoral policy platform, integrating child survival and stunting
      goals within macro-level policies and programmes for reducing poverty and
      improving agricultural productivity, food security, water supply, and sanitation.
      INTERPRETATION: The reduction of under-5 mortality in Ethiopia was the result of
      combined activities in health, nutrition, and non-health sectors. However,
      Ethiopia still has high neonatal and maternal morbidity and mortality from
      preventable causes and an unfinished agenda in reducing inequalities, improving
      coverage of effective interventions, and strengthening multisectoral partnerships
      for further progress. FUNDING: Bill & Melinda Gates Foundation and Government of
      Canada.

PMID- 29025636
TI  - Folic acid grafted and tertiary amino based pH-responsive pentablock polymeric
      micelles for targeting anticancer drug delivery.
AB  - Increasing target to tumor sites and reducing accumulation at normal tissue sites
      of anticancer drugs are essential to improve the cancer chemotherapy efficiency.
      In this study, we have developed a novel pentablock polymeric poly(ethylene
      glycol)-b-(poly(2-(diethylamino) ethyl methacrylate)-b-poly (hydroxyethyl
      methacrylate)-g-folic acid)2 [PEG-b-(PDEAEMA-b-PHEMA-g-FA)2] micelles as
      anticancer drug nanocarrier. The carriers could target tumor cells rapidly, and
      response to the tumor sites pH to control drug release. The critical micelle
      concentration (CMC) of the intermediates copolymers was 4.37-7.08mg/L, which
      indicated that the self-assembled micelles had comparatively good internal
      circulation stability. The drug loaded micelles were prepared using dialysis
      method, resulting in an average particle size of below 120nm, and the drug
      loading content and entrapment efficiency were 21% and 48% respectively. The pH
      responsiveness and in vitro drug release of the micelles were studied, and the
      results showed a higher doxorubicin (DOX) cumulative amount at pH5.0 (~90%)
      compared to pH7.4 (~20%) owing to the protonation of the tertiary amino groups.
      In vitro cytotoxicity and endocytosis experiments showed that the tumor
      suppressing effect of drug-loaded micelles was close to those of free DOX. The
      loaded DOX could be delivered into the cancer cells in a short time, and about
      80% of the tumor cells were killed after 48h incubation. The results indicate
      that the pentablock polymeric micelles have the potential to be applied for
      targeting anticancer drug delivery and control release.

PMID- 29025637
TI  - Electrospun biphasic tubular scaffold with enhanced mechanical properties for
      vascular tissue engineering.
AB  - Polymer scaffolds produced through an electrospinning process are frequently
      explored as tissue substitutes for regenerative medicine. Despite offering
      desirable surface area to volume ratios and tailorable pore sizes, their poor
      structural mechanical properties limit their applicability in load-bearing
      regions. In this study, we present a simple strategy to improve the mechanical
      properties of a vascular graft scaffold. We achieved the formation of biphasic
      tubular scaffolds by electrospinning polyurethane (PU) onto an airbrushed tube
      made of polycaprolactone (PCL). After preparation, the scaffold was subsequently
      thermally-crosslinked (60 degrees C) to strengthen the bonding between the two
      materials. The tensile strength and tensile elastic (Young's) modulus of the
      biphasic scaffolds were significantly enhanced from 4.5+/-1.72 and 45+/-15MPa (PU
      only) up to 67.5+/-2.4 and 1039+/-81.8MPa (PCL/PU; p<0.05). Additionally, suture
      retention force, burst pressure, and compliance were all improved. The
      cytotoxicity of the fabricated samples was investigated using an MTT assay after
      7days of cell culture and found to be negligible (~100% viability). In
      conclusion, we have demonstrated the preparation and characterization of a stable
      and mechanically robust vascular graft scaffold using a novel combination of well
      established fabrication techniques. This study could also be extended to the
      fabrication of other biphasic scaffolds to better enhance the mechanical
      properties of the electrospun fibers mat without deteriorating its architecture
      structure.

PMID- 29025631
TI  - Effect of isoniazid preventive therapy on risk of death in west African, HIV
      infected adults with high CD4 cell counts: long-term follow-up of the Temprano
      ANRS 12136 trial.
AB  - BACKGROUND: Temprano ANRS 12136 was a factorial 2 * 2 trial that assessed the
      benefits of early antiretroviral therapy (ART; ie, in patients who had not
      reached the CD4 cell count threshold used to recommend starting ART, as per the
      WHO guidelines that were the standard during the study period) and 6-month
      isoniazid preventive therapy (IPT) in HIV-infected adults in Cote d'Ivoire. Early
      ART and IPT were shown to independently reduce the risk of severe morbidity at 30
      months. Here, we present the efficacy of IPT in reducing mortality from the long
      term follow-up of Temprano. METHODS: For Temprano, participants were randomly
      assigned to four groups (deferred ART, deferred ART plus IPT, early ART, or early
      ART plus IPT). Participants who completed the trial follow-up were invited to
      participate in a post-trial phase. The primary post-trial phase endpoint was
      death, as analysed by the intention-to-treat principle. We used Cox proportional
      models to compare all-cause mortality between the IPT and no IPT strategies from
      inclusion in Temprano to the end of the follow-up period. FINDINGS: Between March
      18, 2008, and Jan 5, 2015, 2056 patients (mean baseline CD4 count 477 cells per
      MUL) were followed up for 9404 patient-years (Temprano 4757; post-trial phase
      4647). The median follow-up time was 4.9 years (IQR 3.3-5.8). 86 deaths were
      recorded (Temprano 47 deaths; post-trial phase 39 deaths), of which 34 were in
      patients randomly assigned IPT (6-year probability 4.1%, 95% CI 2.9-5.7) and 52
      were in those randomly assigned no IPT (6.9%, 5.1-9.2). The hazard ratio of death
      in patients who had IPT compared with those who did not have IPT was 0.63 (95%
      CI, 0.41 to 0.97) after adjusting for the ART strategy (early vs deferred), and
      0.61 (0.39-0.94) after adjustment for the ART strategy, baseline CD4 cell count,
      and other key characteristics. There was no evidence for statistical interaction
      between IPT and ART (pinteraction=0.77) or between IPT and time
      (pinteraction=0.94) on mortality. INTERPRETATION: In Cote d'Ivoire, where the
      incidence of tuberculosis was last reported as 159 per 100 000 people, 6 months
      of IPT has a durable protective effect in reducing mortality in HIV-infected
      people, even in people with high CD4 cell counts and who have started ART.
      FUNDING: National Research Agency on AIDS and Viral Hepatitis (ANRS).

PMID- 29025638
TI  - Identification of anti-cancer potential of doxazocin: Loading into chitosan based
      biodegradable hydrogels for on-site delivery to treat cervical cancer.
AB  - In this study, an effective, biocompatible and biodegradable co-polymer
      comprising of chitosan (CS) and polyvinyl alcohol (PVA) hydrogels, chemically
      crosslinked and impregnated with doxazocin, is reported. The chemical structural
      properties of the hydrogels were evaluated by Fourier Transform Infrared
      spectroscopy (FTIR) and physical properties were analysed by scanning electron
      microscopy (SEM). The swelling behaviour is an important parameter for drug
      release mechanism and was investigated to find out the solution absorption
      capacity of the synthesized hydrogels. MTT assay revealed that doxazocin loaded
      hydrogels significantly hindered the cell viability. Flow cytometry analysis was
      performed to analyse the effect of 8CLH and 4CLH on regulation of cell cycle.
      Moreover, in vivo anti-cancer potential of synthesized hydrogels was assessed by
      CAM Assay. Results displayed that 8CLH with 1mg/ml of doxazocin had prominently
      decreased the angiogenesis and significantly increased the number of cells in G1
      phase of cell cycle. These results declared that 8CLH will be a good addition
      among hydrogels used for treatment of cancer by onsite delivery of drug.

PMID- 29025639
TI  - Effects of copper nanoparticles in porous TiO2 coatings on bacterial resistance
      and cytocompatibility of osteoblasts and endothelial cells.
AB  - Copper (Cu) has garnered increasing interest due to its excellent antimicrobial
      activity and important roles in human metabolism. Although the biological effects
      of Cu have been studied, the effects of Cu nanoparticles (NPs) on cell behavior
      are not well understood. In this study, porous TiO2 coatings doped with different
      amounts of Cu NPs (designated as 0 Cu, 0.3 Cu, and 3.0 Cu) are deposited on
      titanium by micro-arc oxidation (MAO). The Cu NPs coated samples exhibit
      excellent antibacterial activity against Staphylococcus aureus (S. aureus). In
      vitro cytocompatibility evaluation discloses that 0 Cu and 0.3 Cu have no
      toxicity to osteoblasts but 3.0 Cu shows cytotoxicity. 0.3 Cu promotes
      proliferation and adhesion of osteoblasts and enhances extracellular matrix
      mineralization (ECM), but has little effects on the alkaline phosphatase activity
      (ALP) and collagen secretion. Surprisingly, the Cu NPs coated samples show a
      different behavior with endothelial cells. Both 0.3 Cu and 3.0 Cu show no
      cytotoxicity on endothelial cells and promote cell proliferation. Production of
      nitric oxide (NO) and secretion of vascular endothelial growth factor (VEGF) by
      the endothelial cells are observed from the Cu NPs doped TiO2 coatings.

PMID- 29025640
TI  - Fabrication and preliminary study of a biomimetic tri-layer tubular graft based
      on fibers and fiber yarns for vascular tissue engineering.
AB  - Designing a biomimetic and functional tissue-engineered vascular graft has been
      urgently needed for repairing and regenerating defected vascular tissues.
      Utilizing a multi-layered vascular scaffold is commonly considered an effective
      way, because multi-layered scaffolds can easily simulate the structure and
      function of natural blood vessels. Herein, we developed a novel tri-layer tubular
      graft consisted of Poly(L-lactide-co-caprolactone)/collagen (PLCL/COL) fibers and
      Poly(lactide-co-glycolide)/silk fibroin (PLGA/SF) yarns via a three-step
      electrospinning method. The tri-layer vascular graft consisted of PLCL/COL
      aligned fibers in inner layer, PLGA/SF yarns in middle layer, and PLCL/COL random
      fibers in outer layer. Each layer possessed tensile mechanical strength and
      elongation, and the entire tubular structure provided tensile and compressive
      supports. Furthermore, the human umbilical vein endothelial cells (HUVECs) and
      smooth muscle cells (SMCs) proliferated well on the materials. Fluorescence
      staining images demonstrated that the axially aligned PLCL/COL fibers prearranged
      endothelium morphology in lumen and the circumferential oriented PLGA/SF yarns
      regulated SMCs organization along the single yarns. The outside PLCL/COL random
      fibers performed as the fixed layer to hold the entire tubular structure. The in
      vivo results showed that the tri-layer vascular graft supported cell
      infiltration, scaffold biodegradation and abundant collagen production after
      subcutaneous implantation for 10weeks, revealing the optimal biocompatibility and
      tissue regenerative capability of the tri-layer graft. Therefore, the specially
      designed tri-layer vascular graft will be beneficial to vascular reconstruction.

PMID- 29025641
TI  - Polyurethane foam/nano hydroxyapatite composite as a suitable scaffold for bone
      tissue regeneration.
AB  - In bone tissue regeneration, the use of biomineralized scaffolds to create the 3D
      porous structure needed for well-fitting with defect size and appropriate cell
      interactions, is a promising alternative to autologous and heterologous bone
      grafts. Biomineralized polyurethane (PU) foams are here investigated as scaffold
      for bone tissue regeneration. Biomineralization of the foams was carried out by
      activation of PU surface by a two steps procedure performed for different times
      (1 to 4 weeks). Scaffolds were investigated for morphological, chemico-physical
      and mechanical properties, as well as for in vitro interaction with rat Bone
      Marrow Mesenchymal Stem Cells (BMSCs). Untreated and biomineralized PU samples
      showed a homogenous morphology and regular pore size (average O=407MUm). Phase
      and structure of formed calcium phosphates (CaPs) layer onto the PU foam were
      analyzed by Fourier Transform Infrared spectroscopy and X-ray diffraction,
      proving the formation of bone-like nano hydroxyapatite. Biomineralization caused
      a significant increase of mechanical properties of treated foams compared to
      untreated ones. Biomineralization also affected the PU scaffold cytocompatibility
      providing a more appropriate surface for cell attachment and proliferation.
      Considering the obtained results, the proposed scaffold can be considered
      suitable for bone tissue regeneration.

PMID- 29025642
TI  - Engineered chimeric peptides with antimicrobial and titanium-binding functions to
      inhibit biofilm formation on Ti implants.
AB  - Titanium (Ti) implants have been commonly used in oral medicine. However, despite
      their widespread clinical application, these implants are susceptible to failure
      induced by microbial infection due to bacterial biofilm formation. Immobilization
      of chimeric peptides with antibacterial properties on the Ti surface may be a
      promising antimicrobial approach to inhibit biofilm formation. Here, chimeric
      peptides were designed by connecting three sequences (hBD-3-1/2/3) derived from
      human beta-defensin-3 (hBD-3) with Ti-binding peptide-l (TBP-l: RKLPDAGPMHTW) via
      a triple glycine (G) linker to modify Ti surfaces. Using X-ray photoelectron
      spectroscopy (XPS), the properties of individual domains of the chimeric peptides
      were evaluated for their binding activity toward the Ti surface. The
      antimicrobial and anti-biofilm efficacy of the peptides against initial settlers,
      Streptococcus oralis (S. oralis), Streptococcus gordonii (S. gordonii) and
      Streptococcus sanguinis (S. sanguinis), was evaluated with confocal laser
      scanning microscopy (CLSM) and scanning electron microscopy (SEM). Transmission
      electron microscopy (TEM) and real-time quantitative PCR (qRT-PCR) were used to
      study cell membrane changes and the underlying antimicrobial mechanism. Compared
      with the other two peptides, TBP-1-GGG-hBD3-3 presented stronger antibacterial
      activity and remained stable in saliva and serum. Therefore, it was chosen as the
      best candidate to modify Ti surfaces in this study. This peptide inhibited the
      growth of initial streptococci and biofilm formation on Ti surfaces with no
      cytotoxicity to MC3T3-E1 cells. Disruption of the integrity of bacterial
      membranes and decreased expression of adhesion protein genes from S. gordonii
      revealed aspects of the antibacterial mechanism of TBP-1-GGG-hBD3-3. We conclude
      that engineered chimeric peptides with antimicrobial activity provide a potential
      solution for inhibiting biofilm formation on Ti surfaces to reduce or prevent the
      occurrence of peri-implant diseases.

PMID- 29025643
TI  - Comb-shaped, temperature-tunable and water-soluble porphyrin-based
      thermoresponsive copolymer for enhanced photodynamic therapy.
AB  - A novel comb-shaped porphyrin end-functionalized poly(N-isopropylacrylamide)-b
      poly[oligo (ethylene glycol methyl ether methacrylate)] (Por-PNIPAM-b-POEGMA) was
      synthesized via reversible addition-fragmentation chain transfer (RAFT)
      polymerization. Due to the incorporation of hydrophilic POEGMA contents, the
      copolymer shows the lower critical solution temperatures (LCST) of 37-41.8
      degrees C higher than PNIPAM. Moreover, this copolymer showed efficient singlet
      oxygen under light irradiation at 650nm, and the productivity of singlet oxygen
      was 0.59, which could be used for photodynamic therapy. In addition, the in vitro
      study indicated that this copolymer showed no significant dark cytotoxicity,
      while showed apparent photo-toxicity toward HeLa cancer cells under red light
      irradiation at 650nm. MTT results indicated that this copolymer with appropriate
      LCST could be accumulated on locally tumor tissues and killing of cancer cells
      (Hela), which may be a promising photosensitizer in photodynamic therapy for
      cancer treatment.

PMID- 29025644
TI  - Polylactic acid-based porous scaffolds doped with calcium silicate and dicalcium
      phosphate dihydrate designed for biomedical application.
AB  - Polylactic acid (PLA), dicalcium phosphate dihydrate (DCPD) and/or hydraulic
      calcium silicate (CaSi) have been used to prepare highly-porous scaffolds by
      thermally induced phase separation technique (TIPS). Three experimental mineral
      doped formulations were prepared (PLA-10CaSi, PLA-5CaSi-5DCPD, PLA-10CaSi
      10DCPD). Pure PLA scaffolds constituted the control group. Scaffolds were tested
      for their chemical-physical and biological properties, namely calcium release,
      alkalinizing activity, surface microchemistry and micromorphology by ESEM,
      apatite-forming ability by EDX, micro-Raman and IR spectroscopy, thermal
      properties by differential scanning calorimetry, mechanical properties by quasi
      static parallel-plates compression testing, porosity by a standard water
      absorption method and direct-contact cytotoxicity. All mineral-doped scaffolds
      released biologically relevant ions (biointeractive). A B-type carbonated apatite
      layer (thickness decreasing along the series PLA-10CaSi-10DCPD>PLA-10CaSi>PLA
      5CaSi-5DCPD>PLA) was detected on the surface of all the 28d-aged scaffolds.
      Surface pores of fresh scaffolds ranged from 10 to 20MUm in pure PLA to 10-100MUm
      in PLA-10CaSi. An increase in porosity was detected in 28d-aged pure PLA
      scaffolds (approx. 30% of material loss with decrease of the PLA chain length);
      differently, in mineral-doped scaffolds, the PLA degradation was balanced by
      deposition/nucleation of apatite. All scaffolds showed absence of toxicity, in
      particular PLA-10CaSi-10DCPD. The designed scaffolds are biointeractive (release
      biologically relevant ions), nucleate apatite, possess high surface and internal
      open porosity and can be colonized by cells, appearing interesting materials for
      bone regeneration.

PMID- 29025645
TI  - Enhancing the anti-gastric cancer activity of curcumin with biocompatible and pH
      sensitive PMMA-AA/ZnO nanoparticles.
AB  - Curcumin loaded ZnO nanoparticles were successfully synthesised and encapsulated
      with co-polymer PMMA-AA (Cur/PMMA-AA/ZnO NPs). The ZnO nanoparticles have been
      converted as good cargo materials to carry the well-known hydrophobic drug
      curcumin by surface functionalization. Physical characteristics of these novel
      nanomaterials have been studied with transmission electron microscopy (TEM) and
      powder X-ray diffraction (XRD) in conjunction with spectral techniques. A narrow
      particle size distribution with an average value of 42nm was found via TEM. Most
      importantly, the pH-responsive release of curcumin from the nano-vehicle ensures
      safer, more controlled delivery of the drug at physiological pH. The drug
      entrapment efficiency and loading was evaluated and the in vitro efficacy as
      anticancer drug delivery vehicle was analyzed. The potential toxicity of Cur/PMMA
      AA/ZnO NPs was studied by using AGS gastric cancer cell lines via MTT assay.
      These results revealed that the proposed nanomaterials induce a remarkable cell
      death in in-vitro models. The multifunctional properties of Cur/PMMA-AA/ZnO NPs
      may open up new avenues in cancer therapy through overcoming the limitations of
      conventional cancer therapy.

PMID- 29025646
TI  - Nanographene oxide as a switch for CW/pulsed NIR laser triggered drug release
      from liposomes.
AB  - The application of pulsed and continuous wave (CW) lasers in nanomedicine has
      increased significantly over the last decade. Near infrared (NIR) lasers can be
      used for the precise control of drug release at the target site in a non-invasive
      manner. In this study, we have prepared nanographene oxide (nGO, size ~40nm)
      integrated liposomes (size ~900nm). The nGOs were not simply adsorbed onto the
      liposome surface but was embedded inside the liposomes as characterized by cryo
      TEM, selected area electron diffraction (SAED), and fluorescence quenching
      studies. The embedded nGOs could act as a molecular switch for NIR light
      controlled drug release from the liposomes. Calcein was encapsulated into the
      liposome as a model drug to evaluate the efficiency of light controlled release.
      An on-demand pulsatile drug release was achieved by irradiation of CW/pulsed NIR
      lasers into the nGO-liposome suspension. Triggering with a pulsed laser resulted
      in larger release of calcein with a minimal temperature increase (~2 degrees C)
      of the liposome solution, compared to lower release rate and a significant
      temperature increase (~8 degrees C) by a CW laser with the same light energy,
      suggesting two separate mechanisms and different potential applications depending
      on the laser type.

PMID- 29025647
TI  - Glucose functionalized carbon quantum dot containing organic radical for
      optical/MR dual-modality bioimaging.
AB  - The organic paramagnetic compounds nitroxides have great potential as magnetic
      resonance imaging (MRI) contrast agents. Herein, we report the synthesis and
      characterization of glucose modified carbon quantum dot containing 2,2,6,6
      tetramethyl-piperidinooxy (TEMPO) for targeted bimodal MR/optical imaging of
      tumor cells. CQD-TEMPO-Glu shows the greatest potentials for bioimaging
      applications in view of low cytotoxicity, good biocompatibility, green
      fluorescence emission and high T1 relaxivities. The in vitro MR and optical
      imaging results confirm enhanced cellular internalization of CQD-TEMPO-Glu in
      cancer cells through GLUT mediated endocytosis. These results confirm that CQD
      TEMPO-Glu is expected to be widely exploited as dual-modal contrast for cancer
      imaging.

PMID- 29025648
TI  - Visible light-assisted efficient degradation of dye pollutants with biomass
      supported TiO2 hybrids.
AB  - The objective of this work was to develop a novel organic-inorganic hybrid
      nanomaterial from agricultural biomass waste for environmental applications. The
      sugarcane bagasse (SB) supported TiO2 hybrids were firstly synthesized via a sol
      gel method. A series of characterizations were carried out to reveal the
      structures and components of obtained hybrids. Due to organic-inorganic hybrid
      (OIH) effect and element doping, the SB-TiO2 hybrid can expand its optical
      absorbance ranging from ultraviolet to visible light. The optimal hybrid catalyst
      prepared with SB doping amount of 2g in 100mL titanic gel and calcined at 200
      degrees C was able to degradate 95.0% methyl orange (MO) in 5h under visible
      light. This study will pave a new and facile pathway for novel visible light
      driven photocatalysts based on TiO2 modified by agricultural biomass waste.

PMID- 29025649
TI  - Room temperature preparation of fluorescent starch nanoparticles from starch
      dopamine conjugates and their biological applications.
AB  - Fluorescent organic nanoparticles (FONs) have been regarded as the promising
      candidates for biomedical applications owing to their well adjustment of chemical
      structure and optical properties and good biological properties. However, the
      preparation of FONs from the natural derived polymers has been rarely reported
      thus far. In current work, we reported a novel strategy for preparation of FONs
      based on the self-polymerization of starch-dopamine conjugates and
      polyethyleneimine in rather mild experimental conditions, including air
      atmosphere, aqueous solution, absent catalysts and at room temperature. The
      morphology, chemical structure and optical properties of the resultant starch
      based FONs were investigated by different characterization techniques. Biological
      evaluation results demonstrated that these starch-based FONs possess good
      biocompatibility and fluorescent imaging performance. More importantly, the novel
      strategy might also be extended for the preparation of many other carbohydrate
      polymers based FONs with different structure and functions. Therefore, this work
      opens a new avenue for the preparation and biomedical applications of luminescent
      carbohydrate polymers.

PMID- 29025650
TI  - Ephemeral biogels to control anti-biofilm agent delivery: From conception to the
      construction of an active dressing.
AB  - Chronic wound colonization by bacterial biofilms is common and can cause various
      complications. An anti-biofilm strategy was developed around the co-entrapment of
      a commercially available antiseptic, PHMB (polyhexamethylene biguanide 4mgmL-1),
      with EDTA (Ethylen diamine tetra acetic acid, 20mM) in a gelatin gel. The two
      active compounds act synergistically against bacterial biofilms, but their
      efficiency is strongly reduced (16-fold) when entrapped inside the 5% gelatin
      gel, and they weaken the mechanical properties (50-fold) of the gel. Increasing
      the gelatin concentration to 7% allows for good mechanical properties but large
      diffusional constraints. An active ephemeral gel, a chemical gel with controlled
      hydrolysis, was conceived and developed. When the ephemeral gel was solubilized
      after 48h, PHMB delivery increased, leading to good anti-biofilm activity. The
      various gels were examined over 24 and 48h of contact with P. aeruginosa and S.
      aureus biofilms, two types of bacterial biofilms frequently encountered in
      chronic wounds. The ephemeral gel eradicated the dense biofilms (>6.107CFU.cm-2)
      produced by either single or mixed strains; a similar efficiency was measured for
      biofilms from strains of both laboratory and clinical origin. The formulation was
      then adapted to develop a dressing prototype that is active against biofilms and
      fulfils the requirements of an efficient wound care system.

PMID- 29025651
TI  - Hierarchically porous structure, mechanical strength and cell biological
      behaviors of calcium phosphate composite scaffolds prepared by combination of
      extrusion and porogen burnout technique and enhanced by gelatin.
AB  - In this study, hierarchically porous calcium phosphate scaffolds (HTCP) with
      unidirectional pores, transversely interconnected pores, and micropores were
      fabricated by the combination of extrusion and porogen burnout technique. Gelatin
      was incorporated into the HTCP scaffolds by vacuum-impregnation of gelatin
      solution and subsequent freeze-drying. The phase composition, microstructure,
      physical and cytobiological properties were analyzed. The results showed that the
      HTCP scaffolds were composed of beta-tricalcium phosphate with minor
      hydroxyapatite. The HTCP scaffolds had unidirectional pores (~400MUm),
      transversely interconnected pores (~130MUm) and micropores (~1MUm). The
      incorporation of gelatin significantly increased the compressive strength,
      toughness, and cell seeding of the HTCP scaffolds. The composite scaffolds showed
      excellent cytocompatibility. The hierarchically porous calcium phosphate
      composite scaffolds may have potential application prospects in bone tissue
      engineering.

PMID- 29025652
TI  - High-activity chitosan/nano hydroxyapatite/zoledronic acid scaffolds for
      simultaneous tumor inhibition, bone repair and infection eradication.
AB  - Implanted biomaterials combined tumor inhibition and bone repair property are
      urgently needed to address the huge bone destruction and the high local
      recurrence following primary surgery in bone tumor therapy. In this work, a high
      activity chitosan/nano hydroxyapatite (CS/nHA) scaffold containing zoledronic
      acid (CS/nHA/Zol) was prepared with a facile method. The prepared CS/nHA/Zol
      scaffolds exhibited excellent tumor inhibition property towards giant cell tumor
      of bone (GCT) in vitro through inducing cells apoptosis by up-regulating pro
      apoptosis genes expression and reducing the osteoclastic activity of tumor cells
      by down-regulating osteoclastic genes. Meanwhile, the prepared scaffolds
      possessed well biocompatibility and osteoinductivity as compared to pure CS/nHA
      scaffolds. Furthermore, the prepared scaffolds also presented outstanding
      antibacterial activity against clinical pathogenic S. aureus and E. coli. These
      overall findings successfully demonstrated the prepared CS/nHA/Zol scaffolds had
      a multifunction of tumor therapy, bone repair, and antibacterium, which provides
      a new approach possessed promising advantages in bone tumor therapy.

PMID- 29025653
TI  - Stepwise pH/reduction-responsive polymeric conjugates for enhanced drug delivery
      to tumor.
AB  - In this research, a charge-conversional polymer, poly-l-lysine-lipoic acid (PLL
      LA), was prepared by dimethylmaleic anhydride (DA) modification and applied as a
      carrier with enhanced cell internalization and intracellular pH- and reduction
      triggered doxorubicin (Dox) release. The surface charge of dimethylmaleic
      anhydride-poly-l-lysine-lipoic acid micelles (DA-PLL-LA) was negative at
      physiological pH and reversed to positive at the extracellular and intracellular
      pH of cancer cells. At tumor extracellular pH of 6.8, the conjugates underwent a
      rapid charge-reversible process with almost 80% DA cleavage within 2h, and then
      endocytosed into the endo/lysosomes more rapidly than at physiological pH of 7.4.
      The Dox/DA-PLL-LA micelles (Dox-micelles) demonstrated a sustained drug release
      in vitro under physiological condition, and rapid Dox release was triggered by
      both extracellular pH and high-concentration reducing glutathione. The Dox
      micelles also exhibited enhanced internalization at extracellular pH, rapid
      intracellular drug release, and improved cytotoxicity against A549 cells in
      vitro. Excellent tumor-penetrating efficacy was also found in A549 tumor
      spheroids and solid tumor slices. Moreover, the DA-PLL-LA micelles exhibited
      excellent tumor-targeting ability in tumor tissues and excellent antitumor
      efficacy and low systemic toxicity in breast tumor-bearing mice. Therefore, the
      DA-PLL-LA micelles demonstrated great potential for targeted and efficient drug
      delivery in cancer treatments.

PMID- 29025655
TI  - alpha-Cyclodextrin concentration-controlled thermo-sensitive supramolecular
      hydrogels.
AB  - Supramolecular hydrogels (SHGs) built from inclusion complex of macrocyclic
      compound alpha-cyclodextrin (alpha-CD) and poly(ethylene glycol) (PEG) have
      attracted much interest due to their excellent biocompatibility and great
      potential for biomedical applications. In this work, the hydrogen bond of nucleic
      acid was introduced into the above-mentioned SHG by syntheses of nucleobase
      guanine/cytosine (G/C)-terminated PEG (G-PEG-G/C-PEG-C). The base-pairing
      interaction between G and C as an additional network junction effectively
      enhanced storage moduli (G's) of the hydrogels. Moreover, the prepared hydrogels
      exhibited excellent cytocompatibility and property for controlled drug release,
      outlining the potential of thermo-sensitive construct for biomedical
      applications, such as local chemotherapy of cancers.

PMID- 29025654
TI  - 3D printing hydrogel with graphene oxide is functional in cartilage protection by
      influencing the signal pathway of Rank/Rankl/OPG.
AB  - 3Dprinting is defined as the use of printing technology to deposit living cells,
      and biomaterials on a given /a substrate. Graphene oxide nanoparticles (GO-np)
      have been used as a delivery vehicle for small molecule drugs in order to
      investigate the state of GO-np within 3D tissue constructs in terms of a
      composite 3D printing scaffold, which in turn is relevant to the protection of
      cartilage. We transplanted rats with hydrogel/GO-np and hydrogel, which in turn
      showed that hydrogel/GO-np protected the tissue of cartilage by the signal
      pathway of Rank/Rankl/OPG. Those findings indicated that GO-np may be potentially
      used to control the release of carrier materials and influence the signal pathway
      of Rank/Rankl/OPG.

PMID- 29025657
TI  - Novel fluoridated silk fibroin/ TiO2 nanocomposite scaffolds for bone tissue
      engineering.
AB  - It is known that Fluoride ions strongly affect bone mineralization and formation.
      In the present study, the engineered bone tissue scaffolds are fabricated using
      silk fibroin (SF) and flouridated TiO2 nanoparticles. TiO2 nanoparticles are
      modified by fluoride ions, and different levels (0, 5, 10, 15 and 20wt%) of the
      fluoridated TiO2 nanoparticles (TiO2-F) were subsequently added to the SF matrix
      through phase separation method to prepare silk fibroin/flouridated TiO2
      nanocomposite scaffolds (SF/TiO2-F). Phase structure, functional groups,
      morphology and mechanical properties of the obtained scaffolds were evaluated by
      X-ray diffraction method (XRD), Fourier transform infrared spectroscopy (FTIR),
      scanning electron microscopy (SEM) and compressive testing, respectively. In
      vitro degradation studies of scaffolds were performed by incubating the samples
      in phosphate buffered saline (PBS) at 37 degrees C and pH7.4 for 30days.
      Additionally, the bioactivity of scaffolds was estimated in a simulated body
      fluid (SBF) buffered at 37 degrees C and pH7.4 for 28days. Moreover, MTT assay
      was used to confirm the biocompatibility of the scaffolds using human like SaOS-2
      osteoblast cell line for 1, 3 and 5days. The obtained results indicated that the
      mechanical properties of scaffolds have been improved by increasing the TiO2-F
      amount up to 15wt%. However, a detrimental effect was observed by a further
      increase in the TiO2-F content. The bioactivity of SF/TiO2-F nanocomposite
      scaffolds was promoted by flouridation of TiO2. Furthermore, cell cytotoxicity
      results demonstrated that the SF/TiO2-F nanocomposite scaffolds are nontoxic to
      osteoblasts. The cell fixation results after 3days of incubation revealed that
      the cell attachment and spreading on SF/TiO2-F nanocomposite scaffolds are
      improved with respect to SF/TiO2 nanocomposite scaffolds control sample.

PMID- 29025656
TI  - Dual-delivery of VEGF and NGF by emulsion electrospun nanofibrous scaffold for
      peripheral nerve regeneration.
AB  - Controlled delivery of multiple therapeutic agents can be considered an effective
      approach in nerve injury due to its multifunction. In this study, recombinant
      human vascular endothelial growth factor (VEGF) and recombinant human nerve
      growth factor (NGF) were loaded on the surface and in the core of emulsion
      electrospun poly (l-lactic acid) (PLLA) nanofibrous scaffold, respectively. The
      in vitro studies showed that VEGF and NGF had a sequential release pattern in
      which most of the VEFG was released in the first few days but the NGF could be
      continuously released for >1month. The dual-delivery scaffold could enhance the
      neural differentiation of induced pluripotent stem cells-derived neural crest
      stem cells (iPSCs-NCSCs) in vitro. Furthermore, this scaffold was applied to a
      critical sized defect in rat sciatic nerve model. Footprint analysis,
      electrophysiological tests, and histological analysis revealed that a significant
      improvement of neovascularization as well as nerve healing after 3months post
      operation could be achieved by dual-delivery of VEGF and NGF. Taken together, the
      present study indicated that VEGF and NGF in emulsion electrospun nanofibrous
      scaffold had a synergistic effect on regeneration of vascularized nerve tissue.

PMID- 29025658
TI  - A novel local drug delivery system: Superhydrophobic titanium oxide nanotube
      arrays serve as the drug reservoir and ultrasonication functions as the drug
      release trigger.
AB  - A local drug delivery system consisting of superhydrophobic titanium oxide
      nanotube (S-TNTs) arrays and ultrasonic-controlled release trigger was developed
      in this work. Hydrophilic TNTs arrays are converted into superhydrophobic after
      being treated by 1H,1H,2H,2H- perfluorooctyl-triethoxysilane (POTS). S-TNTs
      arrays serving as a drug-carrying vehicle require no extra sealing treatment due
      to the excellent isolation effect from the trapped air layer on the surface.
      Different amounts of drugs could be loaded into S-TNTs arrays by control of the
      structure of arrays (including length and diameter of tubes) and the original
      amount of drug in the drug-loading solution. The relation between surface
      morphology of TNTs arrays and superhydrophobicity (isolation effect) was
      thoroughly investigated. To achieve a stimulus-responsive drug delivery system,
      ultrasonication was employed as an efficient drug release trigger. Trapped air
      layer could be selectively removed by ultrasonication, and therefore the loaded
      drug could be released in a multiple and controlled manner. Any drugs that can
      dissolve in nonpolar solutions are expected to be suitable for this local drug
      delivery system.

PMID- 29025659
TI  - Multi-responsive hydrogels with UCST- and LCST-induced shrinking and controlled
      release behaviors of rhodamine B.
AB  - By using a disulfide-functionalized crosslinker, a pH- and thermo-responsive 2
      (dimethylamino) ethyl methacrylate (DMAEMA) monomer and a zwitterionic
      sulfobetaine methacrylate (SBMA) monomer were conjugated to fabricate a multi
      responsive P(DMAEMA-SS-SBMA) copolymeric hydrogel. Apparent UCST and LCST volume
      transitions were observed in the P(DMAEMA-SS-SBMA) hydrogels with equivalent
      weight fractions of monomers. Different pore size and response sensitivity of
      shrunken structures below UCST and above LCST were visualized by SEM images. The
      hydrogel exhibited a highly swollen state with a swelling ratio of 17.8 and a
      pore size of 106MUm at 45 degrees C, they deswelled unequally at 5 degrees C with
      a compact surface with pore size of 30MUm and a loose bulk with pore size of
      83MUm, while they deswelled uniformly at 65 degrees C with dense shrunken
      structure with small pore size of 12MUm. The dual-thermoresponsive hydrogel was
      promising in controlled drug release. The initial drug release was predominantly
      controlled by diffusion, and the long-term release was influenced by the swelling
      ratio. Below UCST, the relatively hydrophilic shrunken structure and slow
      diffusion had a synergistic effect on the sustained release. Above LCST, the fast
      diffusion and the rapid "off" effect of hydrophobic skin layer resulted in a
      burst release. Additionally, pH-tunable swelling and redox-sensitive degradation
      were also observed.

PMID- 29025660
TI  - Electrospun carboxyl multi-walled carbon nanotubes grafted polyhydroxybutyrate
      composite nanofibers membrane scaffolds: Preparation, characterization and
      cytocompatibility.
AB  - Electrospun polyhydroxybutyrate (PHB)/carboxyl multi-walled carbon nanotubes
      grafted polyhydroxybutyrate (CMWCNT-g-PHB) composite nanofibers scaffolds were
      fabricated by electrospinning technology. The grafted product CMWCNT-g-PHB was
      prepared by condensation reactions between the carboxyl groups of CMWCNT and
      hydroxyl groups of PHB molecules and characterized by FTIR, XRD, XPS, TG and TEM
      measurements. The surface morphology, hydrophilicity and tensile mechanical
      properties of the electrospun PHB/CMWCNT-g-PHB composite nanofibers membrane
      scaffolds were investigated. The values of tensile strength, breaking elongation
      rate, initial modulus and fracture energy of the composite nanofibers scaffolds
      can reach to 4.64MPa, 255.59%, 88MPa and 109.73kJ/m2, respectively. The
      biodegradability and cytocompatibility of the electrospun composite nanofibers
      scaffolds were preliminarily evaluated. The as-prepared electrospun PHB/CMWCNT-g
      PHB composite nanofibers scaffolds with the characteristics of large specific
      area, high porosity, good biodegradability and cytocompatibility as well as
      sufficient mechanical properties should be more promising in the field of tissue
      engineering scaffolds and biological medicine.

PMID- 29025661
TI  - Low systemic toxicity nanocarriers fabricated from heparin-mPEG and PAMAM
      dendrimers for controlled drug release.
AB  - In this report, poly(amide amine) (PAMAM) dendrimer and Heparin-grafted
      monomethoxy polyethylene glycol (HEP-mPEG) were synthesized and characterized. In
      aqueous solution, the generation 4 PAMAM dendrimers (G4.0-PAMAM) existed as
      nanoparticles with particle size of 5.63nm. However, after electrostatic
      complexation with HEP-mPEG to form a core@shell structure G4.0-PAMAM@HEP-mPEG,
      the size of nanoparticles was significantly increased (73.82nm). The G4.0
      PAMAM@HEP-mPEG nanoparticles showed their ability to effectively encapsulate
      doxorubicin (DOX) for prolonged and controlled release. The cytocompatibility of
      G4.0-PAMAM@HEP-mPEG nanocarriers was significantly increased compared with its
      parentally G4.0-PAMAM dendrimer in both mouse fibroblast NIH3T3 and the human
      tumor HeLa cell lines. DOX was effectively encapsulated into G4.0-PAMAM@HEP-mPEG
      nanoparticles to form DOX-loaded nanocarriers (DOX/G4.0-PAMAM@HEP-mPEG) with high
      loading efficiency (73.2%). The release of DOX from DOX/G4.0-PAMAM@HEP-mPEG
      nanocarriers was controlled and prolonged up to 96h compared with less than 24h
      from their parentally G4.0-PAMAM nanocarriers. Importantly, the released DOX
      retained its bioactivity by inhibiting the proliferation of monolayer-cultured
      cancer HeLa cells with the same degree of fresh DOX. This prepared G4.0-PAMAM@HEP
      mPEG nanocarrier can be a potential candidate for drug delivery systems with high
      loading capacity and low systemic toxicity in cancer therapy.

PMID- 29025662
TI  - Synthesis and characterization of a novel double cross-linked hydrogel based on
      Diels-Alder click reaction and coordination bonding.
AB  - Hydrogels, promising biological materials, need to have both strong mechanical
      properties and also inherent self-healing properties. In this work a double cross
      linked network (DN) hydrogel was designed and prepared by combining a Diels-Alder
      click reaction and coordination effects. This DN hydrogel had good thermodynamic
      properties, anti-EDTA performance and self-healing properties. In addition, the
      mechanical properties, swelling properties and surface morphology of DN hydrogels
      can be controlled by adjusting the ratio of Fe3+-catechol. The adjustment of pH
      value can change the color, crosslinking mode and mechanical properties of the DN
      hydrogel. This smart hydrogel created from DA click chemistry and coordination
      effects has significance for guiding the design of new hydrogels with good
      mechanical properties, self-healing properties and controlled cross-link density.

PMID- 29025663
TI  - Self-assembly of bacitracin-gold nanoparticles and their toxicity analysis.
AB  - As the widely use of gold nanoparticles (AuNPs) in drug delivery, the precise
      control on the size and morphology of the AuNPs is urgently required. In this
      scenario, traditional synthesis methods cannot meet current requirement because
      of their inherent defects. We have depicted here a novel method for fabricating
      monodispersed large size gold nanoparticles, based on the self-assembly of
      bacitracin. The AuNPs could be facilely, low-cost, and green synthesized with
      repeatability and controllability in this method. The Bac gold nanoparticles (Bac
      AuNPs), composed by bacitracin core and gold shell, exhibited a spherical
      morphology in TEM and a face-centered cubic crystal structure in X-Ray
      diffraction and selected area electron diffraction. The mean diameter of the Bac
      AuNPs was 89nm. The nanoparticles were mono-dispersed and the zeta potential of
      the nanoparticles was 4.1+/-0.64mV. Notably, in cell viability assay, the Bac
      AuNPs showed less toxicity to HepG2 cells and HEK293 cells compared to small size
      AuNPs. Collectively, the size, rheological characteristic and the
      biocompatibility supported the use of the gold nanoparticles as intracellular
      delivery vehicles for drug delivery, especially for tumor therapy. And this study
      could provide a maneuverable, controllable and green strategy for the synthesis
      of AuNPs, which would be applied in disease diagnosis and therapy with biosafety.

PMID- 29025664
TI  - Preparation and characterization of gellan gum/glucosamine/clioquinol film as
      oral cancer treatment patch.
AB  - To administer cancer drugs with improved convenience to patients and to enhance
      the bioavailability of cancer drugs for oral cancer therapy, this study prepared
      gellan gum/glucosamine/clioquinol (GG/GS/CQ) film as the oral cancer treatment
      patch. GG/GS/CQ film fabricated through the EDC-mediated coupling reactions
      (GG/GS/CQ/EDC film). The film of the physicochemical properties and drug release
      kinetics were studied. The effectiveness of GG/GS/CQ/EDC film as oral cancer
      treatment patch were evaluated with the animal model. The results confirmed that
      CQ can be incorporated via EDC-mediated covalent conjugation to gellan
      gum/glucosamine. Mechanical testing revealed that the maximum tensile strength
      and elongation percentage at break were 1.91kgf/mm2 and 5.01% for GG/GS/CQ/EDC
      film. After a drug release experiment lasting 45days, 86.8% of CQ was released
      from GG/GS/CQ/EDC film. The Huguchi model fit the GG/GS/CQ/EDC drug release data
      with high correlation coefficients (R2=0.9994, respectively). The effect of the
      CQ dose on oral cancer cells (OC-2) was tested, and the IC50 of CQ alone and CQ
      with 10MUM CuCl2 were 9.59 and 2.22MUM, respectively. The animal testing
      indicated that GG/GS/CQ/EDC film was decreased epidermal growth factor receptor
      (EGFR) expression and suppress tumor progression. These findings provide insights
      into a possible use for GG/GS/CQ/EDC film for oral ca in clinical practice. The
      GG/GS/CQ/EDC film is suitable as the dressing for use in the treatment of early
      stage cancer or as wound care after surgery in late-stage of oral cancer
      treatment.

PMID- 29025665
TI  - Cell attachment evaluation of the immobilized bioactive peptide on a nanographene
      oxide composite.
AB  - The immobilization of bioactive peptides as key molecules in numerous biological
      and physiological functions holds promise for designing advanced biomaterials.
      Graphene and its derivatives, having unique physicochemical properties, have
      brought considerable attention in the life sciences. In this regard, the chemical
      manipulation of the graphene surface with bioactive peptides opens a new horizon
      to design bioactive materials for a variety of future nanobiotechnologies. In
      this study, the first straightforward strategy for the covalent immobilization of
      the cell-adhesion peptide onto the graphene surface based on the Ugi four
      component assembly process (Ugi 4-CAP) will be presented. The modified adhesion
      motif peptide, as an amine component in the presence of formaldehyde,
      cyclohexylisocyanide and carboxylated-graphene (G-COOH), was adopted in a four
      component reaction to fabricate a peptide-graphene (Peptide-G) biomaterial in
      water as a green solvent at an ambient temperature. The amino functional groups
      corresponded to the modified adhesion motif peptide and were immobilized onto the
      graphene sheets, which were quantified by the Kaiser test. The sheets were
      characterized by further analyses with FT-IR, AFM, UV-vis, Raman and
      thermogravimetric analyses. The Peptide-G biomaterial showed excellent
      biocompatibility. In addition, the Peptide-G treated surface, due to the presence
      of RGD on the surface of the graphene, significantly accelerated the
      proliferation of human mesenchymal stem cells (hMSCs) at a better rate regarding
      the tissue plate.

PMID- 29025666
TI  - Comprehensive assessment of electrospun scaffolds hemocompatibility.
AB  - Biodegradable polyesters, namely polycaprolactone (PCL) and copolymer of
      polylactide and polycaprolactone (PLCL) were electrospun into various fibrous
      structures and their hemocompatibility was evaluated in vitro. Firstly, hemolytic
      effect was evaluated upon incubation with diluted whole blood. The results showed
      that the degree of hemolysis depended on chemical composition and fibrous
      morphology. Electrospun polycaprolactone induced slight degree of hemolysis
      depending on its molecular weight and fibrous morphology; copolymer PLCL did not
      cause detectable hemolysis. The influence of coagulation pathways was examined by
      measurement of coagulation times. It was showed that intrinsic coagulation
      pathway assessed by activated partial thromboplastin time (APTT) was moderately
      accelerated after incubation with PCL and prolonged after incubation with
      copolymer PLCL. Extrinsic activation of coagulation tested by prothrombin time
      (PT) was slightly accelerated after incubation with all tested electrospun
      samples. Thrombogenicity assessment of fibrous samples revealed high thrombogenic
      properties of fibrous materials that was comparable to high degree of collagen
      thrombogenicity. The level of platelet activation was dependent on chemical
      composition and surface morphology of tested materials.

PMID- 29025667
TI  - Adhesion forces of biofilms developed in vitro from clinical strains of skin
      wounds.
AB  - A biofilm is a very complex consortium formed by a mix of different
      microorganisms, which have become an important health problem, because its
      formation is a resistance mechanism used by bacteria against antibiotics or the
      immune system. In this work, we show differences between some physicochemical
      properties of biofilms in mono- and multi-species, formed by bacteria from
      clinical samples of infected chronic wounds. Of the most prevalent bacteria in
      wounds, two mono- and one multi-species biofilms were developed in vitro by Drip
      Flow Reactor: one biofilm was developed by S. aureus, other by P. aeruginosa, and
      a third one by the mix of both strains. With these biofilms, we determined
      microbial growth by plate counting, and their physicochemical characterization by
      Atomic Force Microscopy, Raman Micro-Spectroscopy and Scanning Electron
      Microscopy. We found that the viability of S. aureus was less than P. aeruginosa
      in multi-species biofilm. However, the adhesion force of S. aureus is much higher
      than that of P. aeruginosa, but it decreased while that of P. aeruginosa
      increased in the multi-species biofilm. In addition, we found free pyrimidines
      functional groups in the P. aeruginosa biofilm and its mix with S. aureus.
      Surprisingly, each bacterium alone formed single layer biofilms, while the mix
      bacteria formed a multilayer biofilm at the same observation time. Our results
      show the necessity to evaluate biofilms from clinically isolated strains and have
      a better understanding of the adhesion forces of bacteria in biofilm
      multispecies, which could be of prime importance in developing more effective
      treatments against biofilm formation.

PMID- 29025668
TI  - Sustained raloxifene release from hyaluronan-alendronate-functionalized titanium
      nanotube arrays capable of enhancing osseointegration in osteoporotic rabbits.
AB  - To enhance the localized bone remodeling at titanium-based implants under
      osteoporotic conditions, TiO2 nanotube arrays (TNT) were used as nanoreserviors
      for raloxifene (Ral) and then covered with the hybrid multilayered coating of
      chitosan and alendronate grafted hyaluronic acid (HA-Aln) via a spin-assisted
      layer-by-layer technique. The fabrication of this system (TNT/Ral/LBL-Aln) was
      characterized by field emission scanning electron microscopy (SEM), atomic force
      microscope (AFM) and X-ray photoelectron spectroscopy (XPS), respectively. The
      release test showed that the composited multilayers onto Ral-loaded TiO2 nanotube
      substrate (TNT/Ral) could prevent the burst release of Ral from TiO2 nanotube
      arrays and maintain stable Ral concentration at the implant site even after 192h.
      The TNT/Ral/LBL-Aln system demonstrated higher alkaline phosphatase (ALP)
      activity, mineralization capability in osteoblasts as well as lower tartrate
      resistant acid phosphatase (TRAP) activity in osteoclasts compared to both bare
      TiO2 nanotube and TNT/Ral substrate, respectively. Moreover, the in vivo tests of
      micro-CT, histological staining and push-out testing showed that TNT/Ral/LBL-Aln
      implant could efficiently enhance the formation of new bone around the implant
      and promote bone binding in osteoporotic rabbits. The study indicated the
      potential application of TNT/Ral/LBL-Aln system for bone remodeling under
      osteoporotic condition.

PMID- 29025669
TI  - Preparation and evaluation of squid ink polysaccharide-chitosan as a wound
      healing sponge.
AB  - A new type of wound healing agent was developed using two marine biomaterials
      (squid ink polysaccharide and chitosan) as carriers and calcium chloride as an
      initiator for coagulation. Based on central composite design-response surface
      methodology, comprehensive evaluation of appearance quality for composite sponges
      and water absorbency were used as evaluation indices to identify the optimized
      preparation conditions and further evaluate the performance of the squid ink
      polysaccharide-chitosan sponge (SIP-CS). The optimized formulation of SIP-CS was
      as follows: chitosan concentration, 2.29%; squid ink polysaccharide
      concentration, 0.55%; and calcium chloride concentration, 2.82%, at a volume
      ratio of 15:5:2. SIP-CS was conducive to sticking on the wound, characterized by
      the spongy property, strong absorptivity, and tackiness. Rabbit ear arterial,
      hepatic, and femoral artery hemorrhage experiments indicated that, compared with
      chitosan dressings and absorbable gelatin, the hemostatic times were shorter and
      the bleeding volume was smaller. Furthermore, SIP-CS absorbed a large amount of
      hemocytes, leading to rapid hemostasis. The healing areas and wound pathological
      sections in scalded New Zealand rabbits indicated that SIP-CS promoted wound
      healing more rapidly than chitosan and better than commercially available burn
      cream. Thus, SIP-CS is a good wound healing agent for rapid hemostasis, promoting
      burn/scalded skin healing, and protecting from wound infection.

PMID- 29025670
TI  - Bone regeneration: Biomaterials as local delivery systems with improved
      osteoinductive properties.
AB  - Bone is a mineralized conjunctive tissue, with a unique trauma healing
      capability. However, the replacement or regeneration of lost bone is not always
      successful and becomes more difficult the wider the bone defect. A significant
      growth in the demand for orthopedic and maxillofacial surgical procedures as a
      result of population aging and increase in chronic diseases as diabetes is a fact
      and successful approaches for bone regeneration are still needed. Until today,
      autogenous bone graft continues to be the best solution even with important
      limitations, as quantity and the requirement of a donator area. Alternatively,
      local delivery systems combining an osteoconductive biomaterial with
      osteoinductive compounds as hormones, growth factors or drugs is a popular
      approach aiming to replace the need for autogenous bone grafts. Nevertheless, in
      spite of the intense research in the area, presently there is no system that can
      mimic all the biological functions of the autogenous bone grafts. In this
      context, the present work provides an overview of the most recent advances in the
      field of synthetic bone grafts. The opportunities and limitations are detailed
      along with the remaining gaps in the research that are still preventing the
      successful translation of more products into the market able to be a valuable
      option in comparison to the autogenous bone grafts.

PMID- 29025671
TI  - In situ and ex situ modifications of bacterial cellulose for applications in
      tissue engineering.
AB  - Bacterial cellulose (BC) is secreted by a few strains of bacteria and consists of
      a cellulose nanofiber network with unique characteristics. Because of its
      excellent mechanical properties, outstanding biocompatibilities, and abilities to
      form porous structures, BC has been studied for a variety of applications in
      different fields, including the use as a biomaterial for scaffolds in tissue
      engineering. To extend its applications in tissue engineering, native BC is
      normally modified to enhance its properties. Generally, BC modifications can be
      made by either in situ modification during cell culture or ex situ modification
      of existing BC microfibers. In this review we will first provide a brief
      introduction of BC and its attributes; this will set the stage for in-depth and
      up-to-date discussions on modified BC. Finally, the review will focus on in situ
      and ex situ modifications of BC and its applications in tissue engineering,
      particularly in bone regeneration and wound dressing.

PMID- 29025672
TI  - Corrigendum to "Effect of low-intensity pulsed ultrasound on the biological
      behavior of osteoblasts on porous titanium alloy scaffolds: An in vitro and in
      vivo study" [Mater. Sci. Eng. C 80 (2017) 7-17].

PMID- 29025673
TI  - Effects of cetyltrimethylammonium bromide on the morphology of green synthesized
      Fe3O4 nanoparticles used to remove phosphate.
AB  - In this paper, iron oxide nanoparticles (IONPs) are successfully synthesized
      using Eucalyptus leaf extract in the presence of cetyltrimethylammonium bromide
      (CTAB) to enhance the dispersion and reduce aggregation of IONPs. CTAB was used
      as a stabilizing and capping agent in biosynthesis of IONP was observed. The
      particle size decreased from 183.9+/-30.1nm to 89.8+/-17.1nm as the concentration
      of CTAB increased from 0 to 0.4mM CTAB, indicating that CTAB reduce the
      aggregation of IONPs and enhance the reactivity. In addition, the removal
      efficiency of phosphate declined from 95.13% to 89.58% when the CTAB
      concentration increased from 0.4 to 10mM, indicating that a CTAB impacted on
      micelles and lipophilic biomolecules in Eucalyptus leaf extract, and hence
      affected the formation of IONPs. Furthermore, SEM image showed that the smaller
      spherical with some irregularly shaped CTAB-IONPs having a diameter of 80-90nm in
      the presence of 0.4mM CTAB were observed. The date from EDS, FTIR and TGA
      suggested that the CTAB capped on the surface of CTAB-IONPs, while XRD showed
      that zero-valent iron and iron oxide were formed. Finally, the formation
      mechanism of IONPs was proposed.

PMID- 29025674
TI  - Green synthesis of ZnO and Cu-doped ZnO nanoparticles from leaf extracts of
      Abutilon indicum, Clerodendrum infortunatum, Clerodendrum inerme and
      investigation of their biological and photocatalytic activities.
AB  - In the present study, green synthesis and determination of the antioxidant,
      antibacterial, antifungal, anticancer and photocatalytic properties of the
      resultant Cu-doped zinc oxide nanoparticles (NAPs) were carried out. A
      superficial method (solution combustion method) was employed for the synthesis of
      un-doped ZnO NAPs from aqueous extract of Abutilon indicum, and synthesis of Cu
      doped ZnO NAPs from aqueous extracts of Clerodendrum infortunatum (M1 NAPs) and
      Clerodendrum inerme (M2 NAPs). The synthesized un-doped ZnO, M1 and M2 NAPs were
      characterized by different spectroscopic techniques like Ultraviolet-visible (UV
      Vis), Fourier Transform-Infrared (FT-IR), X-ray diffraction (XRD), energy
      dispersive X-ray spectroscopy (EDX) and scanning electron microscopy (SEM). The
      antibacterial and antifungal activities of M1 and M2 NAPs were determined by agar
      diffusion method, while their antioxidant properties were assessed through DPPH
      radical scavenging and ferric thiocyanate (FTC) and assays. Under sunlight
      irradiation, photocatalytic disintegration potential of M1 and M2 NAPs were
      determined by the degradation of Acid Black 234 dye. Results from FT-IR, XRD, EDX
      and SEM confirmed successful synthesis, crystalline nature, and spheroid-to-rod
      like shapes of un-doped ZnO, M1 and M2 NAPs, with grain sizes of 16.72nm, 17.49nm
      and 20.73nm; and band gap energies of 3.37eV, 3.36eV and 3.31eV, respectively.
      The NAPs were good catalysts for effective degradation of Acid Black 234. They
      also exhibited remarkable antioxidant and anticancer activities. Significant
      antibacterial activity was shown by M2 NAPs against E. coli, S. aureus,
      Klebsiella and B. subtilis, with zones of inhibition (ZOIs) of 13+/-0.09, 14+/
      0.01, 18+/-0.07 and 20+/-0.10, respectively. Significant antifungal potential was
      also produced by M2 NAPs at 5mg with ZOIs of 17+/-0.07 and 24+/-0.08 against A.
      niger and T. harzianum, respectively. These results indicate that aqueous
      extracts of A. indicum, C. infortunatum and C. inerme are effective reducing
      agents for green synthesis of un-doped ZnO, and Cu-doped ZnO NAPs with
      significant antimicrobial, antioxidant, and antifungal potential. Thus they are
      good candidates for future therapeutic applications.

PMID- 29025675
TI  - Acetal-linked PEGylated paclitaxel prodrugs forming free-paclitaxel-loaded pH
      responsive micelles with high drug loading capacity and improved drug delivery.
AB  - Endosomal pH-responsive micellar nanoparticles were prepared by self-assembly of
      an amphiphilic poly(ethylene glycol)-acetal-paclitaxel (PEG-acetal-PTX) prodrug,
      and free PTX could be encapsulated in the hydrophobic core of the nanoparticles.
      These nanoparticles exhibited excellent storage stability for over 6months under
      normal conditions, but disassembled quickly in response to faintly acidic
      environment. Incorporating physical encapsulation and chemical conjugation, the
      PTX concentration in the nanoparticles solution could reach as high as
      3665MUg/mL, accompanying with a high drug loading capacity of 60.3%.
      Additionally, benefitting from the difference in drug release mechanism and rate
      between encapsulated PTX and conjugated PTX, a programmed drug release behavior
      was observed, which may result in higher intracellular drug concentration and
      longer action time. CCK-8 assays showed that the nanoparticles demonstrated
      superior antitumor activity than free PTX against both HeLa and MDA-MB-231 cells.
      These prodrug-based nanomedicines have a great potential in developing
      translational PTX formulations for cancer therapy.

PMID- 29025676
TI  - A simple and efficient feeder-free culture system to up-scale iPSCs on polymeric
      material surface for use in 3D bioprinting.
AB  - The 3D bioprinting and cell/tissue printing techniques open new possibilities for
      future applications. To facilitate the 3D bioprinting process, a large amount of
      living cells are required. Induced pluripotent stem cells (iPSCs) represent a
      promising cell source for bioprinting. However, the maintenance and expansion of
      undifferentiated iPSCs are expensive and time consuming. Therefore, in this study
      a culture method to obtain a sufficient amount of healthy and undifferentiated
      iPSCs in a short-term period was established. The iPSCs could be passaged for
      twice on tissue culture polystyrene (TCPS) dish with the conditional medium and
      could adapt to the feeder-free environment. Feeder-free dishes were further
      prepared from chitosan, chitosan-hyaluronan, silk fibroin, and polyurethane (PU1
      and PU2) two-dimensional substrates. The iPSCs cultured on the chitosan
      substrates showed a higher proliferation rate without losing the stemness
      feature. Among the different materials, PU2 could be prepared as a
      thermoresponsive hydrogel, which was a potential ink for 3D bioprinting. The
      iPSCs cultured on PU2 substrates well survived when further embedded in PU2
      hydrogel. Moreover, PU2 hydrogel printed with iPSCs remained structural
      integrity. The use of PU2 hydrogel to embed iPSCs reduced the injury to iPSCs by
      shear stress. These results indicate that iPSCs could be expanded on chitosan or
      PU2 membranes without the feeder layer and then printed in PU2 hydrogel. The
      combination of these steps could offer a new possibility for future applications
      of iPSC-based 3D bioprinting in tissue engineering.

PMID- 29025677
TI  - Degradation of glutamate-based organogels for biodegradable implants: In vitro
      study and in vivo observation.
AB  - Degradation properties play a vital role in long-term in situ drug delivery
      systems. In vitro degradation behaviours of organogels were investigated via two
      approaches in this study: a weight loss method and a drug release method. Through
      the two methods, parameters that affect the degradation of organogels (such as
      gelator type, gelator concentration and oil type) were systematically tested
      under a lipase solution to better mimic in vivo circumstances. The gelator
      structure had the greatest influence on degradation behaviour. By regulating the
      parameters that influence degradation, the drug release method can properly
      predict in vivo degradation. Our investigation of organogel degradation provides
      a theoretical basis for in vivo organogel use as a biodegradable in situ implant
      for drug delivery.

PMID- 29025678
TI  - Effect of crystalline phase changes in titania (TiO2) nanotube coatings on
      platelet adhesion and activation.
AB  - OBJECTIVE: To explore the relationship between various crystalline phases of
      titania (TiO2) nanotube (TNT) coatings and platelet adhesion and activation.
      METHODS: TNT coatings were fabricated on pure titanium foils by anodization and
      then randomly divided into four groups. Three groups were annealed at 350 degrees
      C, 450 degrees C and 550 degrees C in order to obtain different crystalline
      phases. The remaining group was not annealed and served as the control group. X
      ray diffraction (XRD) was used to define the crystalline phases of different
      groups. Surface morphology, elemental composition, surface roughness, and contact
      angles were measured by scanning electron microscopy (SEM), energy dispersive
      spectroscopy (EDS), laser scanning confocal microscopy (LSCM) and contact angle
      analysis, respectively. Platelets were cultured on the TNT coatings for 30min and
      60min to assess the number, viability, distribution, and morphology of the
      adhered platelets. CD62P fluorescence expression and the amount of released
      platelet-derived growth factor (PDGF) were detected to evaluate platelet
      activation. RESULTS: The un-annealed TNT coatings were amorphous and part of TNT
      converted to anatase after the 350 degrees C annealing treatment. The quantity of
      anatase increased upon annealing at 450 degrees C and transformed to rutile at
      550 degrees C. Nanotubes of all four groups maintained a well-ordered structure,
      but the wall thickness of the nanotubes increased from (11.874+/-1.660) nm for
      the un-annealed TNTs to (26.126+/-2.130) nm for the 550 degrees C annealed TNTs.
      The surface roughness of the 550 degrees C annealed TNT coatings was the lowest
      and the water contact angle was the largest at (28.117+/-1.182)  degrees . The
      number and viability of adhered platelets after 30min and 60min were the highest
      on TNT coatings annealed at 450 degrees C. LSCM and SEM images revealed that the
      platelets that adhered on the 450 degrees C annealed TNT coatings aggregated,
      transformed, and spread most obviously. CD62P fluorescence expression results
      showed that the platelets on the 350 degrees C and 450 degrees C annealed TNT
      coating groups expressed the strongest fluorescence, followed by platelets on the
      550 degrees C annealed group and the un-annealed group. The quantity of released
      PDGF was highest for the 450 degrees C annealed group at (4719+/-86) pg/mL, and
      lowest for the un-annealed group at (4241+/-74) pg/mL. CONCLUSION: Crystalline
      TNT coatings encourage improved platelet adhesion and activation over amprphous
      analogues. The TNT coatings annealed at 450 degrees C resulted in the most
      improved platelet behavior. The TNT crystalline phase was the predominant
      influencing factor in platelet adhesion and activation.

PMID- 29025679
TI  - Relation of Residual Mitral Regurgitation Despite Elevated Mitral Gradients to
      Risk of Heart Failure Hospitalization After MitraClip Repair.
AB  - Achieving minimal residual mitral regurgitation (MR) after percutaneous MitraClip
      repair is limited by iatrogenic mitral stenosis. It is unknown whether allowing
      moderately elevated postprocedural mean mitral gradients (MMGs) to achieve <
      moderate residual MR is preferable to moderate residual regurgitation. Patients
      with less-than-moderate residual MR but a MMG of >=5 mm Hg (Group 1) were
      compared with patients with moderate residual MR (Group 2). The primary end point
      was heart failure hospitalization. Secondary end points included mortality,
      subsequent mitral valve surgery, and MR at 1 year. Seventy-eight patients were
      included in the study. Group 1 included 48 patients (median MMG 6, interquartile
      range 5-6 mm Hg). Group 2 included 30 patients (median MMG 3.5, interquartile
      range 2-5 mm Hg). Age, baseline MR severity, and type of MR were not different
      between groups. Freedom from heart failure hospitalization at 1 year was 91.2 +/-
      4.2% in Group 1 versus 70.8 +/- 8.7% in Group 2 (p = 0.021). Achieved differences
      in MR reduction between groups persisted at 1 year (p = 0.007). Survival was not
      different (p = 0.402), and subsequent mitral valve surgery occurred in 4 of 48
      (8%) and in 4 of 30 patients (13%) in Group 1 and Group 2, respectively (p =
      0.476). By multivariate Cox regression analysis, less-than-moderate residual MR,
      despite moderately elevated mitral gradients, was associated with a hazard ratio
      of 0.21 (95% confidence interval 0.04 to 0.96) for subsequent heart failure
      hospitalization (p = 0.044). In conclusion, patients with less-than-moderate
      residual MR despite a MMG of >=5 had a 79% reduction in hazard for subsequent
      heart failure hospitalization compared with patients with moderate residual MR.

PMID- 29025680
TI  - Disorganization of the Retinal Inner Layers as a Predictor of Visual Acuity in
      Eyes With Macular Edema Secondary to Vein Occlusion.

PMID- 29025681
TI  - Physician Assistants and Nurse Practitioners in Ophthalmology-Has the Time Come?

PMID- 29025682
TI  - Corrigendum to "High-temperature EBPR process: The performance, analysis of PAOs
      and GAOs and the fine-scale population study of Candidatus "Accumulibacter
      phosphatis"" [Water Res. 64 (2014) 102-112].

PMID- 29025683
TI  - Corrigendum to "The implications of drought and water conservation on the reuse
      of municipal wastewater: Recognizing impacts and identifying mitigation
      possibilities" [Water Res. 124 (2017), 472-481].

PMID- 29025684
TI  - Ninety-Day Readmission and Long-Term Mortality in Medicare Patients (>=65 Years)
      Treated With Ticagrelor Versus Prasugrel After Percutaneous Coronary Intervention
      (from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium).
AB  - Ticagrelor and prasugrel were found to be superior to clopidogrel for the
      treatment of acute coronary syndrome (ACS) after percutaneous coronary
      intervention (PCI); however, the comparative effectiveness of these 2 drugs
      remains unknown. We compared postdischarge outcomes among older patients treated
      with ticagrelor versus prasugrel after PCI for ACS. We linked clinical data from
      PCIs performed in older patients (age >=65) for ACS at 47 Michigan hospitals to
      Medicare fee-for-service claims from January 1, 2013, to December 31, 2014, to
      ascertain rates of 90-day readmission and long-term mortality. We used propensity
      score matching to adjust for the nonrandom use of ticagrelor and prasugrel at
      discharge. Logistic regression and Cox proportional hazards models were used to
      compare rates of 90-day readmission and long-term mortality, respectively.
      Patients discharged on ticagrelor (n = 1,243) were more frequently older, female,
      had a history of cerebrovascular disease, and presented with ST- or non-ST
      elevation myocardial infarction compared with prasugrel (n = 1,014). After
      matching (n = 756 per group), there were no significant differences in the rates
      of 90-day readmission (16.7% ticagrelor vs 14.6% prasugrel; adjusted odds ratio
      1.15, 95% confidence interval 0.86 to 1.55, p = 0.35) or 1-year mortality (5.4%
      ticagrelor vs 3.7% prasugrel; hazard ratio 1.3, 95% confidence interval 0.8 to
      2.2, p = 0.31). In conclusion, we found no significant differences in the rates
      of 90-day readmission or long-term mortality between older patients treated with
      ticagrelor and patients treated with prasugrel after PCI for ACS. In the absence
      of randomized data to the contrary, these 2 treatments appear similarly
      effective.

PMID- 29025686
TI  - [Usefulness of spectral tissue Doppler (E/e' ratio) in the management of patients
      with atrial fibrillation].
AB  - Atrial fibrillation is the most common cardiac rhythm disorder encountered in
      daily clinical practice. It carries high morbidity and mortality rates, mainly
      related to sudden death, heart failure and stroke. Validation of noninvasive
      markers in the diagnosis of heart failure with preserved ejection fraction and
      risk stratification is therefore attractive in this clinical setting. The
      spectral tissue Doppler-derived E/e' ratio is a simple and user-friendly index
      which has been validated in the assessment of left ventricular diastolic
      pressures, regardless of rhythm. A septal E/e' >11 is associated with invasive
      left ventricular diastolic pressures >15mmHg in patients with atrial
      fibrillation. Several studies have reported the clinical relevance of abnormal
      values of E/e' at rest and during exercise in the diagnosis and risk
      stratification of heart failure with preserved ejection fraction in patients with
      atrial fibrillation. There is now convincing evidence that increased E/e' is
      associated with adverse outcome in patients with atrial fibrillation and predicts
      the recurrence of arrhythmia after cardioversion or catheter ablation. In
      conclusion, we recommend the measurement of E/e' in each patient with atrial
      fibrillation referred for clinically indicated transthoracic Doppler
      echocardiography.

PMID- 29025685
TI  - Generalization of learned pain modulation depends on explicit learning.
AB  - The experience of pain is strongly influenced by contextual and socio-affective
      factors, including learning from previous experiences. Pain is typically
      perceived as more intense when preceded by a conditioned cue (CSHIGH) that has
      previously been associated with higher pain intensities, compared to cues
      associated with lower intensities (CSLOW). In three studies (total N=134), we
      tested whether this learned pain modulation generalizes to perceptually similar
      cues (Studies 1 and 2) and conceptually similar cues (Study 3). The results
      showed that participants report higher pain when heat stimulation was preceded by
      novel stimuli that were either perceptually (Studies 1 and 2) or conceptually
      (Study 3) similar to the previously conditioned CSHIGH. In all three studies, the
      strength of this generalization effect was strongly correlated with individual
      differences in explicitly learned expectations. Together, these findings suggest
      an important role of conscious expectations and higher-order conceptual inference
      during generalization of learned pain modulation. We discuss implications for the
      understanding of placebo and nocebo effects as well as for chronic pain and
      anxiety.

PMID- 29025688
TI  - Altered Medial Frontal Feedback Learning Signals in Anorexia Nervosa.
AB  - BACKGROUND: In their relentless pursuit of thinness, individuals with anorexia
      nervosa (AN) engage in maladaptive behaviors (restrictive food choices and
      overexercising) that may originate in altered decision making and learning.
      METHODS: In this functional magnetic resonance imaging study, we employed
      computational modeling to elucidate the neural correlates of feedback learning
      and value-based decision making in 36 female patients with AN and 36 age-matched
      healthy volunteers (12-24 years). Participants performed a decision task that
      required adaptation to changing reward contingencies. Data were analyzed within a
      hierarchical Gaussian filter model that captures interindividual variability in
      learning under uncertainty. RESULTS: Behaviorally, patients displayed an
      increased learning rate specifically after punishments. At the neural level,
      hemodynamic correlates for the learning rate, expected value, and prediction
      error did not differ between the groups. However, activity in the posterior
      medial frontal cortex was elevated in AN following punishment. CONCLUSIONS: Our
      findings suggest that the neural underpinning of feedback learning is selectively
      altered for punishment in AN.

PMID- 29025687
TI  - Serine Racemase and D-serine in the Amygdala Are Dynamically Involved in Fear
      Learning.
AB  - BACKGROUND: The amygdala is a central component of the neural circuitry that
      underlies fear learning. N-methyl-D-aspartate receptor-dependent plasticity in
      the amygdala is required for pavlovian fear conditioning and extinction. N-methyl
      D-aspartate receptor activation requires the binding of a coagonist, D-serine,
      which is synthesized from L-serine by the neuronal enzyme serine racemase (SR).
      However, little is known about SR and D-serine function in the amygdala. METHODS:
      We used immunohistochemical methods to characterize the cellular localization of
      SR and D-serine in the mouse and human amygdala. Using biochemical and molecular
      techniques, we determined whether trace fear conditioning and extinction engages
      the SR/D-serine system in the brain. D-serine was administered systemically to
      mice to evaluate its effect on fear extinction. Finally, we investigated whether
      the functional single nucleotide polymorphism rs4523957, which is an expression
      quantitative trait locus of the human serine racemase (SRR) gene, was associated
      with fear-related phenotypes in a highly traumatized human cohort. RESULTS: We
      demonstrate that approximately half of the neurons in the amygdala express SR,
      including both excitatory and inhibitory neurons. We find that the acquisition
      and extinction of fear memory engages the SR/D-serine system in the mouse
      amygdala and that D-serine administration facilitates fear extinction. We also
      demonstrate that the SRR single nucleotide polymorphism, rs4523957, is associated
      with posttraumatic stress disorder in humans, consistent with the facilitatory
      effect of D-serine on fear extinction. CONCLUSIONS: These new findings have
      important implications for understanding D-serine-mediated N-methyl-D-aspartate
      receptor plasticity in the amygdala and how this system could contribute to
      disorders with maladaptive fear circuitry.

PMID- 29025689
TI  - SOHO State of the Art Update and Next Questions: Biology and Treatment of
      Myelodysplastic Syndromes.
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms
      characterized by clonal hematopoiesis leading to bone marrow dysplasia and
      cytopenias. Recently, significant advancements have been made in understanding
      the pathogenic mechanisms of this disease. In particular, how a wide array of
      somatic mutations can induce a common clinical phenotype has been investigated.
      Specifically, activation of innate immune signaling (i.e. myeloid derived
      suppressor cells) and the NLRP3 inflammasome in hematopoietic stem/progenitor
      cells play a central role in the biology of MDS, leading to pyroptotic cell death
      and clonal expansion. Additionally, deciphering the molecular drivers of MDS
      using next-generation sequencing has rapidly expanded our understanding of MDS
      with profound implications for prognosis, treatment decisions, and future
      clinical investigations. Together, unraveling of the role of innate
      immunity/pyroptosis in the clinical phenotype of MDS patients and comprehensive
      molecular characterization has identified novel therapeutic strategies that offer
      significant promise.

PMID- 29025690
TI  - Discussion of: "Addressing the quality and cost of cholecystectomy at a safety
      net hospital".

PMID- 29025692
TI  - Prevalence of Actinic Keratosis in Different Regions of Spain: The EPIQA Study.

PMID- 29025691
TI  - Morphea and Extragenital Lichen Sclerosus et Atrophicus After Influenza
      Vaccination.

PMID- 29025694
TI  - Desire to Be Underweight: Exploratory Study on a Weight Loss App Community and
      User Perceptions of the Impact on Disordered Eating Behaviors.
AB  - BACKGROUND: Mobile health (mHealth) apps for weight loss (weight loss apps) can
      be useful diet and exercise tools for individuals in need of losing weight. Most
      studies view weight loss app users as these types of individuals, but not all
      users have the same needs. In fact, users with disordered eating behaviors who
      desire to be underweight are also utilizing weight loss apps; however, few
      studies give a sense of the prevalence of these users in weight loss app
      communities and their perceptions of weight loss apps in relation to disordered
      eating behaviors. OBJECTIVE: The aim of this study was to provide an analysis of
      users' body mass indices (BMIs) in a weight loss app community and examples of
      how users with underweight BMI goals perceive the impact of the app on disordered
      eating behaviors. METHODS: We focused on two aspects of a weight loss app
      (DropPounds): profile data and forum posts, and we moved from a broader picture
      of the community to a narrower focus on users' perceptions. We analyzed profile
      data to better understand the goal BMIs of all users, highlighting the prevalence
      of users with underweight BMI goals. Then we explored how users with a desire to
      be underweight discussed the weight loss app's impact on disordered eating
      behaviors. RESULTS: We found three main results: (1) no user (regardless of start
      BMI) starts with a weight gain goal, and most users want to lose weight; (2)
      6.78% (1261/18,601) of the community want to be underweight, and most identify as
      female; (3) users with underweight BMI goals tend to view the app as positive,
      especially for reducing bingeing; however, some acknowledge its role in
      exacerbating disordered eating behaviors. CONCLUSIONS: These findings are
      important for our understanding of the different types of users who utilize
      weight loss apps, the perceptions of weight loss apps related to disordered
      eating, and how weight loss apps may impact users with a desire to be
      underweight. Whereas these users had underweight goals, they often view the app
      as helpful in reducing disordered eating behaviors, which led to additional
      questions. Therefore, future research is needed.

PMID- 29025693
TI  - Characterizing Active Ingredients of eHealth Interventions Targeting Persons With
      Poorly Controlled Type 2 Diabetes Mellitus Using the Behavior Change Techniques
      Taxonomy: Scoping Review.
AB  - BACKGROUND: The behavior change technique taxonomy v1 (BCTTv1; Michie and
      colleagues, 2013) is a comprehensive tool to characterize active ingredients of
      interventions and includes 93 labels that are hierarchically clustered into 16
      hierarchical clusters. OBJECTIVE: The aim of this study was to identify the
      active ingredients in electronic health (eHealth) interventions targeting
      patients with poorly controlled type 2 diabetes mellitus (T2DM) and relevant
      outcomes. METHODS: We conducted a scoping review using the BCTTv1. Randomized
      controlled trials (RCTs), studies with or pre-post-test designs, and quasi
      experimental studies examining efficacy and effectiveness of eHealth
      interventions for disease management or the promotion of relevant health
      behaviors were identified by searching PubMed, Web of Science, and PsycINFO.
      Reviewers independently screened titles and abstracts for eligibility using
      predetermined eligibility criteria. Data were extracted following a data
      extraction sheet. The BCTTv1 was used to characterize active ingredients of the
      interventions reported in the included studies. RESULTS: Of the 1404 unique
      records screened, 32 studies fulfilled the inclusion criteria and reported
      results on the efficacy and or or effectiveness of interventions. Of the included
      32 studies, 18 (56%) were Web-based interventions delivered via personal digital
      assistant (PDA), tablet, computer, and/or mobile phones; 7 (22%) were telehealth
      interventions delivered via landline; 6 (19%) made use of text messaging (short
      service message, SMS); and 1 employed videoconferencing (3%). Of the 16
      hierarchical clusters of the BCTTv1, 11 were identified in interventions included
      in this review. Of the 93 individual behavior change techniques (BCTs), 31 were
      identified as active ingredients of the interventions. The most common BCTs
      identified were instruction on how to perform behavior, adding objects to the
      environment, information about health consequences, self-monitoring of the
      outcomes and/or and prefers to be explicit to avoid ambiguity. Response: Checked
      and avoided of a certain behavior Author: Please note that the journal
      discourages the use of parenthesis to denote either and/or and prefers to be
      explicit to avoid ambiguity. Response: Checked and avoided "and/or" and prefers
      to be explicit to avoid ambiguity. Response: Checked and avoided, and feedback on
      outcomes of behavior. CONCLUSIONS: Our results suggest that the majority of BCTs
      employed in interventions targeting persons with T2DM revolve around the
      promotion of self-regulatory behavior to manage the disease or to assist patients
      in performing health behaviors necessary to prevent further complications of the
      disease. Detailed reporting of the BCTs included in interventions targeting this
      population may facilitate the replication and further investigation of such
      interventions.

PMID- 29025695
TI  - Exploring the Potential of a Wearable Camera to Examine the Early Obesogenic Home
      Environment: Comparison of SenseCam Images to the Home Environment Interview.
AB  - BACKGROUND: The obesogenic home environment is usually examined via self-report,
      and objective measures are required. OBJECTIVE: This study explored whether the
      wearable camera SenseCam can be used to examine the early obesogenic home
      environment and whether it is useful for validation of self-report measures.
      METHODS: A total of 15 primary caregivers of young children (mean age of child 4
      years) completed the Home Environment Interview (HEI). Around 12 days after the
      HEI, participants wore the SenseCam at home for 4 days. A semistructured
      interview assessed participants' experience of wearing the SenseCam. Intraclass
      correlation coefficients (ICCs), percent agreement, and kappa statistics were
      used as validity estimates for 54 home environment features. RESULTS: Wearing the
      SenseCam was generally acceptable to those who participated. The SenseCam
      captured all 54 HEI features but with varying detail; 36 features (67%) had
      satisfactory validity (ICC or kappa >=0.40; percent agreement >=80 where kappa
      could not be calculated). Validity was good or excellent (ICC or kappa >=0.60)
      for fresh fruit and vegetable availability, fresh vegetable variety, display of
      food and drink (except sweet snacks), family meals, child eating lunch or dinner
      while watching TV, garden and play equipment, the number of TVs and DVD players,
      and media equipment in the child's bedroom. Validity was poor (ICC or kappa
      <0.40) for tinned and frozen vegetable availability and variety, and sweet snack
      availability. CONCLUSIONS: The SenseCam has the potential to objectively examine
      and validate multiple aspects of the obesogenic home environment. Further
      research should aim to replicate the findings in a larger, representative sample.

PMID- 29025696
TI  - Usability Test of Exercise Games Designed for Rehabilitation of Elderly Patients
      After Hip Replacement Surgery: Pilot Study.
AB  - BACKGROUND: Patients who receive rehabilitation after hip replacement surgery are
      shown to have increased muscle strength and better functional performance.
      However, traditional physiotherapy is often tedious and leads to poor adherence.
      Exercise games, provide ways for increasing the engagement of elderly patients
      and increase the uptake of rehabilitation exercises. OBJECTIVE: The objective of
      this study was to evaluate Fietsgame (Dutch for cycling game), which translates
      existing rehabilitation exercises into fun exercise games. The system connects
      exercise games with a patient's personal record and a therapist interface by an
      Internet of Things server. Thus, both the patient and physiotherapist can monitor
      the patient's medical status. METHODS: This paper describes a pilot study that
      evaluates the usability of the Fietsgame. The study was conducted in a
      rehabilitation center with 9 participants, including 2 physiotherapists and 7
      patients. The patients were asked to play 6 exercise games, each lasting about 5
      min, under the guidance of a physiotherapist. The mean age of the patients was
      74.57 years (standard deviation [SD] 8.28); all the patients were in the recovery
      process after hip surgery. Surveys were developed to quantitatively measure the
      usability factors, including presence, enjoyment, pain, exertion, and technology
      acceptance. Comments on advantages and suggested improvements of our game system
      provided by the physiotherapists and patients were summarized and their
      implications were discussed. RESULTS: The results showed that after successfully
      playing the games, 75% to 100% of the patients experienced high levels of
      enjoyment in all the games except the squats game. Patients reported the highest
      level of exertion in squats when compared with other exercise games. Lunges
      resulted in the highest dropout rate (43%) due to interference with the Kinect v2
      from support chairs. All the patients (100%) found the game system useful and
      easy to use, felt that it would be a useful tool in their further rehabilitation,
      and expressed that they would like to use the game in the future. The therapists
      indicated that the exercise games highly meet the criteria of motor
      rehabilitation, and they intend to continue using the game as part of their
      rehabilitation treatment of patients. Comments from the patients and
      physiotherapists suggest that real-time corrective feedback when patients perform
      the exercises wrongly and a more personalized user interface with options for
      increasing or decreasing cognitive load are needed. CONCLUSIONS: The results
      suggest that Fietsgame can be used as an alternative tool to traditional motor
      rehabilitation for patients with hip surgery. Lunges and squats are found to be
      more beneficial for patients who have relatively better balance skills. A follow
      up randomized controlled study will be conducted to test the effectiveness of the
      Fietsgame to investigate how motivating it is over a longer period of time.

PMID- 29025697
TI  - Predicting Consumer Effort in Finding and Paying for Health Care: Expert
      Interviews and Claims Data Analysis.
AB  - BACKGROUND: For consumers to accept and use a health care information system, it
      must be easy to use, and the consumer must perceive it as being free from effort.
      Finding health care providers and paying for care are tasks that must be done to
      access treatment. These tasks require effort on the part of the consumer and can
      be frustrating when the goal of the consumer is primarily to receive treatments
      for better health. OBJECTIVE: The aim of this study was to determine the factors
      that result in consumer effort when finding accessible health care. Having an
      understanding of these factors will help define requirements when designing
      health information systems. METHODS: A panel of 12 subject matter experts was
      consulted and the data from 60 million medical claims were used to determine the
      factors contributing to effort. RESULTS: Approximately 60 million claims were
      processed by the health care insurance organization in a 12-month duration with
      the population defined. Over 292 million diagnoses from claims were used to
      validate the panel input. The results of the study showed that the number of
      people in the consumer's household, number of visits to providers outside the
      consumer's insurance network, number of adjusted and denied medical claims, and
      number of consumer inquiries are a proxy for the level of effort in finding and
      paying for care. The effort level, so measured and weighted per expert panel
      recommendations, differed by diagnosis. CONCLUSIONS: This study provides an
      understanding of how consumers must put forth effort when engaging with a health
      care system to access care. For higher satisfaction and acceptance results,
      health care payers ideally will design and develop systems that facilitate an
      understanding of how to avoid denied claims, educate on the payment of claims to
      avoid adjustments, and quickly find providers of affordable care.

PMID- 29025700
TI  - Synergistic divergence: case series and literature review.
AB  - BACKGROUND: To present the data of a series of patients with synergistic
      divergence, to propose a different modality of surgical correction and to perform
      a literature review of such a rare entity. METHODS: A retrospective study was
      performed on all patients who presented with unilateral or bilateral synergistic
      divergence to the Ophthalmology Department, Cairo University, during the period
      from January 2007 to July 2016. The demographic data, the results of sensorimotor
      examination, the surgical procedures performed and the ophthalmological as well
      as the systemic findings of all patients were collected and tabulated. PubMed was
      searched for patients with features of synergistic divergence. RESULTS: Thirteen
      patients with features of synergistic divergence were identified. The mean age of
      the patients was 8.9+/-10.1 years (range 1-40 years). Only one case was
      orthotropic in the primary position. Lateral rectus orbital wall fixation
      combined with 8-10 mm medial rectus resection was done in 10 patients. The mean
      follow-up was 6.6+/-7.7 months. Exotropia was significantly reduced in all
      patients. All patients had complete disappearance of synergistic divergence after
      surgery. A total of 78 patients with features of synergistic divergence were
      identified from PubMed. Surgery was done for 37 patients. Synergistic divergence
      disappeared in patients who had lateral rectus extirpation or orbital wall
      fixation. CONCLUSION: Synergistic divergence is a challenging rare condition. We
      propose that lateral rectus orbital wall fixation combined with medial rectus
      resection both improves the alignment in primary position and eliminates the
      synergistic divergence in such patients.

PMID- 29025699
TI  - Adoption, Acceptability, and Effectiveness of a Mobile Health App for
      Personalized Prostate Cancer Survivorship Care: Protocol for a Realist Case Study
      of the Ned App.
AB  - BACKGROUND: By 2030, prostate cancer will be the most commonly diagnosed cancer
      in North America. To mitigate this impending challenge, comprehensive support
      mechanisms for disease- and treatment-specific changes in health and well-being
      must be proactively designed and thoughtfully implemented for streamlined
      survivorship care. mHealth apps have been lauded as a promising complement to
      current outpatient treatment and monitoring strategies, but have not yet been
      widely used to support prostate cancer survivorship needs. A realist evaluation
      is needed to examine the impact of such apps on the prostate cancer survivorship
      experience. OBJECTIVE: We seek to gain an understanding of how an mHealth app for
      prostate cancer survivorship care called Ned (No Evident Disease) is adopted and
      accepted by patients, caregivers, and clinicians. We also aim to determine the
      effect of Ned on health-related quality of life, satisfaction with cancer care,
      unmet needs, self-efficacy, and prostate cancer-related levels of anxiety.
      METHODS: The Ned case study is a 12-month mixed-methods embedded single-case
      study with a nested within-group pre-post comparison of health outcomes. We will
      give 400 patients, 200 caregivers, and 10 clinicians access to Ned. Participants
      will be asked to complete study assessments at baseline, 2 months, 6 months, and
      12 months. We will conduct 30 semistructured qualitative interviews with patients
      (n=20) and their caregivers (n=10) poststudy to gain insight into their
      experience with the app. RESULTS: We recruited our first survivor in October 2017
      and anticipate completing this study by May 2019. CONCLUSIONS: This will, to our
      knowledge, be the first realist case study to evaluate an app for prostate cancer
      survivorship care. Prostate cancer survivors are set to increase in number and
      longevity, heightening the need for integrated survivorship solutions to provide
      them with optimal and durable outcomes. The knowledge gained from this study will
      comprehensively inform how and why Ned works, for whom, and in what
      circumstances. Understanding the impact of digital health interventions such as
      Ned on how survivors care for themselves is critical to realizing patient
      centered care.

PMID- 29025698
TI  - College Freshmen Students' Perspectives on Weight Gain Prevention in the Digital
      Age: Web-Based Survey.
AB  - BACKGROUND: College freshmen are highly vulnerable to experiencing weight gain,
      and this phenomenon is associated with an increased risk of chronic diseases and
      mortality in older adulthood. Technology offers an attractive and scalable way to
      deliver behavioral weight gain prevention interventions for this population.
      Weight gain prevention programs that harness the appeal and widespread reach of
      Web-based technologies (electronic health or eHealth) are increasingly being
      evaluated in college students. Yet, few of these interventions are informed by
      college students' perspectives on weight gain prevention and related lifestyle
      behaviors. OBJECTIVE: The objective of this study was to assess college freshmen
      students' concern about weight gain and associated topics, as well as their
      interest in and delivery medium preferences for eHealth programs focused on these
      topics. METHODS: Web-based surveys that addressed college freshmen students'
      (convenience sample of N=50) perspectives on weight gain prevention were
      administered at the beginning and end of the fall 2015 semester as part of a
      longitudinal investigation of health-related issues and experiences in first
      semester college freshmen. Data on weight gain prevention-related concerns and
      corresponding interest in eHealth programs targeting topics of potential concern,
      as well as preferred program delivery medium and current technology use were
      gathered and analyzed using descriptive statistics. RESULTS: A considerable
      proportion of the freshmen sample expressed concern about weight gain (74%,
      37/50) and both traditional (healthy diet: 86%, 43/50; physical activity: 64%,
      32/50) and less frequently addressed (stress: 82%, 41/50; sleep: 74%, 37/50;
      anxiety and depression: 60%, 30/50) associated topics within the context of
      behavioral weight gain prevention. The proportion of students who reported
      interest in eHealth promotion programs targeting these topics was also generally
      high (ranging from 52% [26/50] for stress management to 70% [35/50] for eating a
      healthy diet and staying physically active). Email was the most frequently used
      electronic platform, with 96% (48/50) of students reporting current use of it.
      Email was also the most frequently cited preferred eHealth delivery platform,
      with 86% (43/50) of students selecting it. Facebook was preferred by the second
      greatest proportion of students (40%, 20/50). CONCLUSIONS: Most college freshmen
      have concerns about an array of weight gain prevention topics and are generally
      open to the possibility of receiving eHealth interventions designed to address
      their concerns, preferably via email compared with popular social media
      platforms. These preliminary findings offer a foundation to build upon when it
      comes to future descriptive investigations focused on behavioral weight gain
      prevention among college freshmen in the digital age.

PMID- 29025702
TI  - Oral health of children in England: a call to action!

PMID- 29025701
TI  - Distribution of H3K27me3, H3K9me3, and H3K4me3 along autophagy-related genes
      highly expressed in starved zebrafish myotubes.
AB  - The zebrafish (Danio rerio) remains the teleost fish of choice for biological
      investigations due to the vast array of molecular tools and resources available.
      To better understand the epigenetic regulation of autophagy, we utilized a
      primary myotube culture system generated from isolated myogenic precursor cells
      (MPCs) from zebrafish grown under starvation conditions using a media devoid of
      serum and amino acids. Here, we report starvation-induced regulation of several
      autophagy-related genes (atg) expression and profile the distribution of
      H3K27me3, H3K9me3, and H3K4me3 marks along lc3b, atg4b and p62/sqstm1 loci. These
      data support epigenetic regulation of autophagy in response to starvation that
      suggests a level of regulation that can be sustained for chronic conditions via
      chromatin modification.

PMID- 29025703
TI  - Give GPs more time with patients, urges RCGP chair.

PMID- 29025704
TI  - Improving quality of life relies on valid outcome measures as well as drugs.

PMID- 29025705
TI  - Differentiation, Evaluation, and Application of Human Induced Pluripotent Stem
      Cell-Derived Endothelial Cells.
AB  - The emergence of induced pluripotent stem cell (iPSC) technology paves the way to
      generate large numbers of patient-specific endothelial cells (ECs) that can be
      potentially delivered for regenerative medicine in patients with cardiovascular
      disease. In the last decade, numerous protocols that differentiate EC from iPSC
      have been developed by many groups. In this review, we will discuss several
      common strategies that have been optimized for human iPSC-EC differentiation and
      subsequent studies that have evaluated the potential of human iPSC-EC as a cell
      therapy or as a tool in disease modeling. In addition, we will emphasize the
      importance of using in vivo vessel-forming ability and in vitro clonogenic colony
      forming potential as a gold standard with which to evaluate the quality of human
      iPSC-EC derived from various protocols.

PMID- 29025706
TI  - NO Augments Endothelial Reactivity by Reducing Myoendothelial Calcium Signal
      Spreading: A Novel Role for Cx37 (Connexin 37) and the Protein Tyrosine
      Phosphatase SHP-2.
AB  - OBJECTIVE: Because of its strategic position between endothelial and smooth
      muscle cells in microvessels, Cx37 (Connexin 37) plays an important role in
      myoendothelial gap junctional intercellular communication. We have shown before
      that NO inhibits gap junctional intercellular communication through gap junctions
      containing Cx37. However, the underlying mechanism is not yet identified.
      APPROACH AND RESULTS: Using channel-forming Cx37 mutants exhibiting partial
      deletions or amino acid exchanges in their C-terminal loops, we now show that the
      phosphorylation state of a tyrosine residue at position 332 (Y332) in the C
      terminus of Cx37 controls the gap junction-dependent spread of calcium signals.
      Mass spectra revealed that NO protects Cx37 from dephosphorylation at Y332 by
      inhibition of the protein tyrosine phosphatase SHP-2. Functionally, the
      inhibition of gap junctional intercellular communication by NO decreased the
      spread of the calcium signal (induced by mechanical stimulation of individual
      endothelial cells) from endothelial to smooth muscle cells in intact vessels,
      while, at the same time, augmenting the calcium signal spreading within the
      endothelium. Consequently, preincubation of small resistance arteries with
      exogenous NO enhanced the endothelium-dependent dilator response to acetylcholine
      in spite of a pharmacological blockade of NO-dependent cGMP formation by the
      soluable guanylyl cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1
      one). CONCLUSIONS: Our results identify a novel mechanism by which NO can
      increase the efficacy of calcium, rising vasoactive agonists in the microvascular
      endothelium.

PMID- 29025707
TI  - Proatherogenic Flow Increases Endothelial Stiffness via Enhanced CD36-Mediated
      Uptake of Oxidized Low-Density Lipoproteins.
AB  - OBJECTIVE: Disturbed flow (DF) is well-known to induce endothelial dysfunction
      and synergistically with plasma dyslipidemia facilitate plaque formation. Little
      is known, however, about the synergistic impact of DF and dyslipidemia on
      endothelial biomechanics. Our goal was to determine the impact of DF on
      endothelial stiffness and evaluate the role of dyslipidemia/oxLDL (oxidized low
      density lipoprotein) in this process. APPROACH AND RESULTS: Endothelial elastic
      modulus of intact mouse aortas ex vivo and of human aortic endothelial cells
      exposed to laminar flow or DF was measured using atomic force microscopy.
      Endothelial monolayer of the aortic arch is found to be significantly stiffer
      than the descending aorta (4.2+1.1 versus 2.5+0.2 kPa for aortic arch versus
      descending aorta) in mice maintained on low-fat diet. This effect is
      significantly exacerbated by short-term high-fat diet (8.7+2.5 versus 4.5+1.2 kPa
      for aortic arch versus descending aorta). Exposure of human aortic endothelial
      cells to DF in vitro resulted in 50% increase in oxLDL uptake and significant
      endothelial stiffening in the presence but not in the absence of oxLDL. DF also
      increased the expression of oxLDL receptor CD36 (cluster of differentiation 36),
      whereas downregulation of CD36 abrogated DF-induced endothelial oxLDL uptake and
      stiffening. Furthermore, genetic deficiency of CD36 abrogated endothelial
      stiffening in the aortic arch in vivo in mice fed either low-fat diet or high-fat
      diet. We also show that the loss of endothelial stiffening in CD36 knockout
      aortas is not mediated by the loss of CD36 in circulating cells. CONCLUSIONS: DF
      facilitates endothelial CD36-dependent uptake of oxidized lipids resulting in
      local increase of endothelial stiffness in proatherogenic areas of the aorta.

PMID- 29025709
TI  - Reduction of In-Stent Restenosis by Cholesteryl Ester Transfer Protein
      Inhibition.
AB  - OBJECTIVE: Angioplasty and stent implantation, the most common treatment for
      atherosclerotic lesions, have a significant failure rate because of restenosis.
      This study asks whether increasing plasma high-density lipoprotein (HDL) levels
      by inhibiting cholesteryl ester transfer protein activity with the anacetrapib
      analog, des-fluoro-anacetrapib, prevents stent-induced neointimal hyperplasia.
      APPROACH AND RESULTS: New Zealand White rabbits received normal chow or chow
      supplemented with 0.14% (wt/wt) des-fluoro-anacetrapib for 6 weeks. Iliac artery
      endothelial denudation and bare metal steel stent deployment were performed after
      2 weeks of des-fluoro-anacetrapib treatment. The animals were euthanized 4 weeks
      poststent deployment. Relative to control, dietary supplementation with des
      fluoro-anacetrapib reduced plasma cholesteryl ester transfer protein activity and
      increased plasma apolipoprotein A-I and HDL cholesterol levels by 53+/-6.3% and
      120+/-19%, respectively. Non-HDL cholesterol levels were unaffected. Des-fluoro
      anacetrapib treatment reduced the intimal area of the stented arteries by 43+/
      5.6% (P<0.001), the media area was unchanged, and the arterial lumen area
      increased by 12+/-2.4% (P<0.05). Des-fluoro-anacetrapib treatment inhibited
      vascular smooth muscle cell proliferation by 41+/-4.5% (P<0.001). Incubation of
      isolated HDLs from des-fluoro-anacetrapib-treated animals with human aortic
      smooth muscle cells at apolipoprotein A-I concentrations comparable to their
      plasma levels inhibited cell proliferation and migration. These effects were
      dependent on scavenger receptor-B1, the adaptor protein PDZ domain-containing
      protein 1, and phosphatidylinositol-3-kinase/Akt activation. HDLs from des-fluoro
      anacetrapib-treated animals also inhibited proinflammatory cytokine-induced human
      aortic smooth muscle cell proliferation and stent-induced vascular inflammation.
      CONCLUSIONS: Inhibiting cholesteryl ester transfer protein activity in New
      Zealand White rabbits with iliac artery balloon injury and stent deployment
      increases HDL levels, inhibits vascular smooth muscle cell proliferation, and
      reduces neointimal hyperplasia in an scavenger receptor-B1, PDZ domain-containing
      protein 1- and phosphatidylinositol-3-kinase/Akt-dependent manner.

PMID- 29025708
TI  - Intermuscular Adipose Tissue and Subclinical Coronary Artery Calcification in
      Midlife: The CARDIA Study (Coronary Artery Risk Development in Young Adults).
AB  - OBJECTIVE: Excess deposition of fat within and around vital organs and nonadipose
      tissues is hypothesized to contribute to cardiovascular disease (CVD) risk. We
      evaluated the association of abdominal intermuscular adipose tissue (IMAT) volume
      with coronary artery calcification in the CARDIA study (Coronary Artery Risk
      Development in Young Adults) participants. APPROACH AND RESULTS: We measured IMAT
      in the abdominal muscles, visceral adipose tissue and pericardial adipose tissue,
      and coronary artery calcification using computed tomography in 3051 CARDIA
      participants (56% women) at the CARDIA year 25 examination (2010-2011). Mean IMAT
      volume and mean IMAT/total muscle volume (IMAT normalized for muscle size) were
      calculated in a 10-mm block of slices centered at L3-L4. Multivariable analyses
      included potential confounders and traditional cardiovascular disease risk
      factors. Compared with the lowest quartile, the upper quartile of abdominal IMAT
      volume was associated with higher coronary artery calcification prevalence (odds
      ratio [95% confidence interval], 1.6 [1.2-2.1]) after adjusting for
      cardiovascular disease risk factors. Results were similar for highest versus
      lowest quartile of IMAT normalized to total muscle volume (odds ratio [95%
      confidence interval], 1.5 [1.1-2.0]). Significant associations of higher IMAT and
      normalized IMAT with coronary artery calcification prevalence persisted when body
      mass index, visceral adipose tissue, or pericardial adipose tissue were added to
      the models. CONCLUSIONS: In a large, community-based, cross-sectional study, we
      found that higher abdominal skeletal muscle adipose tissue volume was associated
      with subclinical atherosclerosis independent of traditional cardiovascular
      disease risk factors and other adipose depots.

PMID- 29025710
TI  - Opposing Actions of AKT (Protein Kinase B) Isoforms in Vascular Smooth Muscle
      Injury and Therapeutic Response.
AB  - OBJECTIVE: Drug-eluting stent delivery of mTORC1 (mechanistic target of rapamycin
      complex 1) inhibitors is highly effective in preventing intimal hyperplasia after
      coronary revascularization, but adverse effects limit their use for systemic
      vascular disease. Understanding the mechanism of action may lead to new treatment
      strategies. We have shown that rapamycin promotes vascular smooth muscle cell
      differentiation in an AKT2-dependent manner in vitro. Here, we investigate the
      roles of AKT (protein kinase B) isoforms in intimal hyperplasia. APPROACH AND
      RESULTS: We found that germ-line-specific or smooth muscle-specific deletion of
      Akt2 resulted in more severe intimal hyperplasia compared with control mice after
      arterial denudation injury. Conversely, smooth muscle-specific Akt1 knockout
      prevented intimal hyperplasia, whereas germ-line Akt1 deletion caused severe
      thrombosis. Notably, rapamycin prevented intimal hyperplasia in wild-type mice
      but had no therapeutic benefit in Akt2 knockouts. We identified opposing roles
      for AKT1 and AKT2 isoforms in smooth muscle cell proliferation, migration,
      differentiation, and rapamycin response in vitro. Mechanistically, rapamycin
      induced MYOCD (myocardin) mRNA expression. This was mediated by AKT2
      phosphorylation and nuclear exclusion of FOXO4 (forkhead box O4), inhibiting its
      binding to the MYOCD promoter. CONCLUSIONS: Our data reveal opposing roles for
      AKT isoforms in smooth muscle cell remodeling. AKT2 is required for rapamycin's
      therapeutic inhibition of intimal hyperplasia, likely mediated in part through
      AKT2-specific regulation of MYOCD via FOXO4. Because AKT2 signaling is impaired
      in diabetes mellitus, this work has important implications for rapamycin therapy,
      particularly in diabetic patients.

PMID- 29025711
TI  - Toll-like receptor 2 and 4 have opposing roles in the pathogenesis of cigarette
      smoke-induced chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is the third leading cause of
      morbidity and death and imposes major socioeconomic burdens globally. It is a
      progressive and disabling condition that severely impairs breathing and lung
      function. There is a lack of effective treatments for COPD, which is a direct
      consequence of the poor understanding of the underlying mechanisms involved in
      driving the pathogenesis of the disease. Toll-like receptor (TLR)2 and TLR4 are
      implicated in chronic respiratory diseases, including COPD, asthma and pulmonary
      fibrosis. However, their roles in the pathogenesis of COPD are controversial and
      conflicting evidence exists. In the current study, we investigated the role of
      TLR2 and TLR4 using a model of cigarette smoke (CS)-induced experimental COPD
      that recapitulates the hallmark features of human disease. TLR2, TLR4, and
      associated coreceptor mRNA expression was increased in the airways in both
      experimental and human COPD. Compared with wild-type (WT) mice, CS-induced
      pulmonary inflammation was unaltered in TLR2-deficient ( Tlr2-/-) and TLR4
      deficient ( Tlr4-/-) mice. CS-induced airway fibrosis, characterized by increased
      collagen deposition around small airways, was not altered in Tlr2-/- mice but was
      attenuated in Tlr4-/- mice compared with CS-exposed WT controls. However, Tlr2-/-
      mice had increased CS-induced emphysema-like alveolar enlargement, apoptosis, and
      impaired lung function, while these features were reduced in Tlr4-/- mice
      compared with CS-exposed WT controls. Taken together, these data highlight the
      complex roles of TLRs in the pathogenesis of COPD and suggest that activation of
      TLR2 and/or inhibition of TLR4 may be novel therapeutic strategies for the
      treatment of COPD.

PMID- 29025714
TI  - Racial/ethnic disparities: need more work!

PMID- 29025713
TI  - Neutrophil elastase increases airway ceramide levels via upregulation of serine
      palmitoyltransferase.
AB  - Altered sphingolipid metabolism is associated with increased inflammation;
      however, the impact of inflammatory mediators, including neutrophil elastase
      (NE), on airway sphingolipid homeostasis remains unknown. Using a well
      characterized mouse model of NE oropharyngeal aspiration, we investigated a
      potential link between NE-induced airway inflammation and increased synthesis of
      various classes of sphingolipids, including ceramide species. Sphingolipids in
      bronchoalveolar lavage fluids (BAL) were identified and quantified using reverse
      phase high-performance liquid chromatography/electrospray ionization tandem mass
      spectrometry analysis. BAL total and differential cell counts, CXCL1/keratinocyte
      chemoattractant (KC) protein levels, and high-mobility group box 1 (HMGB1)
      protein levels were determined. NE exposure increased BAL long-chain ceramides,
      total cell and neutrophil counts, and upregulated KC and HMGB1. The mRNA and
      protein levels of serine palmitoyltransferase (SPT) long-chain subunits 1 and 2,
      the multimeric enzyme responsible for the first, rate-limiting step of de novo
      ceramide generation, were determined by qRT-PCR and Western analyses,
      respectively. NE increased lung SPT long-chain subunit 2 (SPTLC2) protein levels
      but not SPTLC1 and had no effect on mRNA for either subunit. To assess whether de
      novo ceramide synthesis was required for NE-induced inflammation, myriocin, a SPT
      inhibitor, or a vehicle control was administered intraperitoneally 2 h before NE
      administration. Myriocin decreased BAL d18:1/22:0 and d18:1/24:1 ceramide, KC,
      and HMGB1 induced by NE exposure. These results support a feed-forward cycle of
      NE-generated ceramide and ceramide-driven cytokine signaling that may be a
      potential target for intervention in lung disease typified by chronic
      neutrophilic inflammation.

PMID- 29025715
TI  - RUNX1 in T-ALL: tumor suppressive or oncogenic?

PMID- 29025716
TI  - Twins actin' differently.

PMID- 29025717
TI  - Impacting inhibitor development in hemophilia A.

PMID- 29025718
TI  - Vorinostat is victorious in GVHD prevention.

PMID- 29025719
TI  - AML with myelodysplasia-related changes masquerades as acute panmyelosis with
      myelofibrosis.

PMID- 29025712
TI  - Ion channels of the lung and their role in disease pathogenesis.
AB  - Maintenance of normal epithelial ion and water transport in the lungs includes
      providing a thin layer of surface liquid that coats the conducting airways. This
      airway surface liquid is critical for normal lung function in a number of ways
      but, perhaps most importantly, is required for normal mucociliary clearance and
      bacterial removal. Preservation of the appropriate level of hydration, pH, and
      viscosity for the airway surface liquid requires the proper regulation and
      function of a battery of different types of ion channels and transporters. Here
      we discuss how alterations in ion channel/transporter function often lead to lung
      pathologies.

PMID- 29025720
TI  - Health Care Economics: A Study Guide for Neuroradiology Fellows, Part 1.
AB  - Few resources are available in the medical literature for a comprehensive review
      of current health care economics as it relates to radiologists, specifically
      framed by topics defined by the Accreditation Council for Graduate Medical
      Education in the evaluation of neuroradiology fellows. Therefore, we present a
      comprehensive review article as a study guide for fellows to learn from and gain
      competence in the Accreditation Council for Graduate Medical Education
      neuroradiology milestones on health care economics.

PMID- 29025721
TI  - Predictive Models in Differentiating Vertebral Lesions Using Multiparametric MRI.
AB  - BACKGROUND AND PURPOSE: Conventional MR imaging has high sensitivity but limited
      specificity in differentiating various vertebral lesions. We aimed to assess the
      ability of multiparametric MR imaging in differentiating spinal vertebral lesions
      and to develop statistical models for predicting the probability of malignant
      vertebral lesions. MATERIALS AND METHODS: One hundred twenty-six consecutive
      patients underwent multiparametric MRI (conventional MR imaging, diffusion
      weighted MR imaging, and in-phase/opposed-phase imaging) for vertebral lesions.
      Vertebral lesions were divided into 3 subgroups: infectious, noninfectious
      benign, and malignant. The cutoffs for apparent diffusion coefficient (expressed
      as 10-3 mm2/s) and signal intensity ratio values were calculated, and 3
      predictive models were established for differentiating these subgroups. RESULTS:
      Of the lesions of the 126 patients, 62 were infectious, 22 were noninfectious
      benign, and 42 were malignant. The mean ADC was 1.23 +/- 0.16 for infectious,
      1.41 +/- 0.31 for noninfectious benign, and 1.01 +/- 0.22 mm2/s for malignant
      lesions. The mean signal intensity ratio was 0.80 +/- 0.13 for infectious, 0.75
      +/- 0.19 for noninfectious benign, and 0.98 +/- 0.11 for the malignant group. The
      combination of ADC and signal intensity ratio showed strong discriminatory
      ability to differentiate lesion type. We found an area under the curve of 0.92
      for the predictive model in differentiating infectious from malignant lesions and
      an area under the curve of 0.91 for the predictive model in differentiating
      noninfectious benign from malignant lesions. On the basis of the mean ADC and
      signal intensity ratio, we established automated statistical models that would be
      helpful in differentiating vertebral lesions. CONCLUSIONS: Our study shows that
      multiparametric MRI differentiates various vertebral lesions, and we established
      prediction models for the same.

PMID- 29025722
TI  - Blunt Cerebrovascular Injuries: Advances in Screening, Imaging, and Management
      Trends.
AB  - Blunt cerebrovascular injury is a relatively uncommon but sometimes life
      threatening injury, particularly in patients presenting with ischemic symptoms in
      that vascular territory. The decision to pursue vascular imaging (generally CT
      angiography) is based on clinical and imaging findings. Several grading scales or
      screening criteria have been developed to guide the decision to pursue vascular
      imaging, as well as to recommend different treatment options for various
      injuries. The data supporting many of these guidelines and options are limited
      however. The purpose of this article is to review and compare these scales and
      criteria and the data supporting clinical efficacy and to make recommendations
      for future research in this area.

PMID- 29025723
TI  - Setting the Stage for 2018: How the Changes in the American Joint Committee on
      Cancer/Union for International Cancer Control Cancer Staging Manual Eighth
      Edition Impact Radiologists.
AB  - The updated eighth edition of the Cancer Staging Manual of the American Joint
      Committee on Cancer will be implemented in January 2018. There are multiple
      changes to the head and neck section of the manual, which will be relevant to
      radiologists participating in multidisciplinary head and neck tumor boards and
      reading pretreatment head and neck cancer scans. Human papillomavirus
      related/p16(+) oropharyngeal squamous cell carcinoma will now be staged
      separately; this change reflects the markedly better prognosis of these tumors
      compared with non-human papillomavirus/p16(-) oropharyngeal squamous cell
      carcinoma. Nodal staging has dramatically changed so that there are different
      tables for human papillomavirus/p16(+) oropharyngeal squamous cell carcinoma,
      Epstein-Barr virus-related nasopharyngeal carcinoma, and all other head and neck
      squamous cell carcinomas. Extranodal extension of tumor is a new clinical feature
      for this third staging group. In the oral cavity, the pathologically determined
      depth of tumor invasion is a new staging criterion, while extrinsic tongue muscle
      invasion is no longer part of staging. This review serves to educate radiologists
      on the eighth edition changes and their rationale.

PMID- 29025725
TI  - CT Texture Analysis: Defining and Integrating New Biomarkers for Advanced
      Oncologic Imaging in Precision Medicine: A Comment on "CT Texture Analysis
      Potentially Predicts Local Failure in Head and Neck Squamous Cell Carcinoma
      Treated with Chemoradiotherapy".

PMID- 29025724
TI  - Correlation between Clinical Outcomes and Baseline CT and CT Angiographic
      Findings in the SWIFT PRIME Trial.
AB  - BACKGROUND AND PURPOSE: Patient selection for endovascular therapy remains a
      great challenge in clinic practice. We sought to determine the effect of baseline
      CT and angiography on outcomes in the Solitaire With the Intention for
      Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT
      PRIME) trial and to identify patients who would benefit from endovascular stroke
      therapy. MATERIALS AND METHODS: The primary end point was a 90-day modified
      Rankin Scale score of 0-2. Subgroup and classification and regression tree
      analysis was performed on baseline ASPECTS, site of occlusion, clot length,
      collateral status, and onset-to-treatment time. RESULTS: Smaller baseline infarct
      (n = 145) (ASPECTS 8-10) was associated with better outcomes in patients treated
      with thrombectomy versus IV tPA alone (66% versus 41%; rate ratio, 1.62) compared
      with patients with larger baseline infarcts (n = 44) (ASPECTS 6-7) (42% versus
      21%; rate ratio, 1.98). The benefit of thrombectomy over IV tPA alone did not
      differ significantly by ASPECTS. Stratification by occlusion location also showed
      benefit with thrombectomy across all groups. Improved outcomes after thrombectomy
      occurred in patients with clot lengths of >=8 mm (71% versus 43%; rate ratio,
      1.67). Outcomes stratified by collateral status had a benefit with thrombectomy
      across all groups: none-fair collaterals (33% versus 0%), good collaterals (58%
      versus 44%), and excellent collaterals (82% versus 28%). Using a 3-level
      classification and regression tree analysis, we observed optimal outcomes in
      patients with favorable baseline ASPECTS, complete/near-complete recanalization
      (TICI 2b/3), and early treatment (mean mRS, 1.35 versus 3.73), while univariate
      and multivariate logistic regression showed significantly better results in
      patients with higher ASPECTS. CONCLUSIONS: While benefit was seen with
      endovascular therapy across multiple subgroups, the greatest response was
      observed in patients with a small baseline core infarct, excellent collaterals,
      and early treatment.

PMID- 29025726
TI  - Gestational Age at Birth and Brain White Matter Development in Term-Born Infants
      and Children.
AB  - BACKGROUND AND PURPOSE: Studies on infants and children born preterm have shown
      that adequate gestational length is critical for brain white matter development.
      Less is known regarding how variations in gestational age at birth in term
      infants and children affect white matter development, which was evaluated in this
      study. MATERIALS AND METHODS: Using DTI tract-based spatial statistics methods,
      we evaluated white matter microstructures in 2 groups of term-born (>=37 weeks of
      gestation) healthy subjects: 2-week-old infants (n = 44) and 8-year-old children
      (n = 63). DTI parameters including fractional anisotropy, mean diffusivity, axial
      diffusivity, and radial diffusivity were calculated by voxelwise and ROI methods
      and were correlated with gestational age at birth, with potential confounding
      factors such as postnatal age and sex controlled. RESULTS: Fractional anisotropy
      values, which are markers for white matter microstructural integrity, positively
      correlated (P < .05, corrected) with gestational age at birth in most major white
      matter tracts/regions for the term infants. Mean diffusivity values, which are
      measures of water diffusivities in the brain, and axial and radial diffusivity
      values, which are markers for axonal growth and myelination, respectively,
      negatively correlated (P < .05, corrected) with gestational age at birth in all
      major white matter tracts/regions excluding the body and splenium of the corpus
      callosum for the term infants. No significant correlations with gestational age
      were observed for any tracts/regions for the term-born 8-year-old children.
      CONCLUSIONS: Our results indicate that longer gestation during the normal term
      period is associated with significantly greater infant white matter development
      (as reflected by higher fractional anisotropy and lower mean diffusivity, axial
      diffusivity, and radial diffusivity values); however, similar associations were
      not observable in later childhood.

PMID- 29025727
TI  - CT Texture Analysis Potentially Predicts Local Failure in Head and Neck Squamous
      Cell Carcinoma Treated with Chemoradiotherapy.
AB  - BACKGROUND AND PURPOSE: The accurate prediction of prognosis and failure is
      crucial for optimizing treatment strategies for patients with cancer. The purpose
      of this study was to assess the performance of pretreatment CT texture analysis
      for the prediction of treatment failure in primary head and neck squamous cell
      carcinoma treated with chemoradiotherapy. MATERIALS AND METHODS: This
      retrospective study included 62 patients diagnosed with primary head and neck
      squamous cell carcinoma who underwent contrast-enhanced CT examinations for
      staging, followed by chemoradiotherapy. CT texture features of the whole primary
      tumor were measured using an in-house developed Matlab-based texture analysis
      program. Histogram, gray-level co-occurrence matrix, gray-level run-length, gray
      level gradient matrix, and Laws features were used for texture feature
      extraction. Receiver operating characteristic analysis was used to identify the
      optimal threshold of any significant texture parameter. We used multivariate Cox
      proportional hazards models to examine the association between the CT texture
      parameter and local failure, adjusting for age, sex, smoking, primary tumor
      stage, primary tumor volume, and human papillomavirus status. RESULTS: Twenty-two
      patients (35.5%) developed local failure, and the remaining 40 (64.5%) showed
      local control. Multivariate analysis revealed that 3 histogram features
      (geometric mean [hazard ratio = 4.68, P = .026], harmonic mean [hazard ratio =
      8.61, P = .004], and fourth moment [hazard ratio = 4.56, P = .048]) and 4 gray
      level run-length features (short-run emphasis [hazard ratio = 3.75, P = .044],
      gray-level nonuniformity [hazard ratio = 5.72, P = .004], run-length
      nonuniformity [hazard ratio = 4.15, P = .043], and short-run low gray-level
      emphasis [hazard ratio = 5.94, P = .035]) were significant predictors of outcome
      after adjusting for clinical variables. CONCLUSIONS: Independent primary tumor CT
      texture analysis parameters are associated with local failure in patients with
      head and neck squamous cell carcinoma treated with chemoradiotherapy.

PMID- 29025728
TI  - Necessary Catheter Diameters for Mechanical Thrombectomy with ADAPT.
AB  - BACKGROUND AND PURPOSE: Large-bore catheters allow mechanical thrombectomy in
      ischemic stroke by engaging and retrieving clots without additional devices
      (direct aspiration first-pass technique [ADAPT]). The purpose of this study was
      to establish a model for minimal catheter diameters needed for ADAPT. MATERIALS
      AND METHODS: We established a theoretic model for the calculation of minimal
      catheter diameters needed for ADAPT. We then verified its validity in 28 ADAPT
      maneuvers in a porcine in vivo model. To account for different mechanical
      thrombectomy techniques, we factored in ADAPT with/without a hypothetic 0.021
      inch microcatheter or 0.014-inch microwire inside the lumen of the aspiration
      catheter and aspiration with a 60-mL syringe versus an aspiration pump. RESULTS:
      According to our calculations, catheters with an inner diameter of >0.040 inch
      and >0.064 inch, respectively, are needed to be effective in the middle cerebral
      artery (2.5-mm diameter) or in the internal carotid artery (4 mm) in an average
      patient. There was a significant correlation between predicted and actual
      thrombectomy results (P = .010). Our theoretic model had a positive and negative
      predictive value of 78% and 79%, respectively. Sensitivity and specificity were
      88% and 64%, respectively. CONCLUSIONS: Our theoretic model allows estimating the
      minimal catheter diameters needed for successful mechanical thrombectomy with
      ADAPT, as demonstrated by the good agreement with our animal experiments. Our
      model will be helpful to interventionalists in avoiding selecting catheters that
      are likely too small to be effective.

PMID- 29025729
TI  - Live cell imaging of cytosolic NADH/NAD+ ratio in hepatocytes and liver slices.
AB  - Fatty liver disease (FLD), the most common chronic liver disease in the United
      States, may be caused by alcohol or the metabolic syndrome. Alcohol is oxidized
      in the cytosol of hepatocytes by alcohol dehydrogenase (ADH), which generates
      NADH and increases cytosolic NADH/NAD+ ratio. The increased ratio may be
      important for development of FLD, but our ability to examine this question is
      hindered by methodological limitations. To address this, we used the genetically
      encoded fluorescent sensor Peredox to obtain dynamic, real-time measurements of
      cytosolic NADH/NAD+ ratio in living hepatocytes. Peredox was expressed in
      dissociated rat hepatocytes and HepG2 cells by transfection, and in mouse liver
      slices by tail-vein injection of adeno-associated virus (AAV)-encoded sensor.
      Under control conditions, hepatocytes and liver slices exhibit a relatively low
      (oxidized) cytosolic NADH/NAD+ ratio as reported by Peredox. The ratio responds
      rapidly and reversibly to substrates of lactate dehydrogenase (LDH) and sorbitol
      dehydrogenase (SDH). Ethanol causes a robust dose-dependent increase in cytosolic
      NADH/NAD+ ratio, and this increase is mitigated by the presence of NAD+
      generating substrates of LDH or SDH. In contrast to hepatocytes and slices, HepG2
      cells exhibit a relatively high (reduced) ratio and show minimal responses to
      substrates of ADH and SDH. In slices, we show that comparable results are
      obtained with epifluorescence imaging and two-photon fluorescence lifetime
      imaging (2p-FLIM). Live cell imaging with Peredox is a promising new approach to
      investigate cytosolic NADH/NAD+ ratio in hepatocytes. Imaging in liver slices is
      particularly attractive because it allows preservation of liver microanatomy and
      metabolic zonation of hepatocytes. NEW & NOTEWORTHY We describe and validate a
      new approach for measuring free cytosolic NADH/NAD+ ratio in hepatocytes and
      liver slices: live cell imaging with the fluorescent biosensor Peredox. This
      approach yields dynamic, real-time measurements of the ratio in living,
      functioning liver cells, overcoming many limitations of previous methods for
      measuring this important redox parameter. The feasibility of using Peredox in
      liver slices is particularly attractive because slices allow preservation of
      hepatic microanatomy and metabolic zonation of hepatocytes.

PMID- 29025730
TI  - Apelin-13 inhibits gastric motility through vagal cholinergic pathway in rats.
AB  - The expression of apelin and its receptors (APJ) in central autonomic networks
      suggests that apelin may regulate gastrointestinal motor functions. In rodents,
      central administration of apelin-13 has been shown to inhibit gastric emptying;
      however, the mechanisms involved remain to be determined. Using male adult
      Sprague-Dawley rats, the aims of the present study were 1) to determine the
      expression of APJ receptor in the dorsal vagal complex (DVC), 2) to assess the
      effects of central application of apelin-13 into the DVC on gastric tone and
      motility, and 3) to investigate the neuronal pathways responsible for apelin
      induced alterations. APJ receptor immunoreactivity was detected in gastric
      projecting and choline acetyltransferase-positive neurons of the DVC.
      Microinjection of apelin-13 into the DVC significantly decreased gastric tone and
      motility in both corpus and antrum. The apelin-induced reduction in gastric tone
      and motility was prevented by surgical vagotomy or fourth ventricular application
      of the APJ receptor antagonist, [Ala13]apelin-13 (F13A). Systemic administration
      of the muscarinic receptor antagonist atropine, but not the nitric oxide synthase
      inhibitor nitro-l-arginine methyl ester (l-NAME), abolished the apelin-induced
      inhibitory responses. The present results indicate a central modulatory role of
      apelin in the vagal neurocircuitry that controls gastric motor functions via
      withdrawal of the tonically active cholinergic pathway. NEW & NOTEWORTHY This is
      the first study investigating the effects induced by brain stem application of
      apelin-13 while monitoring gastric tone and motility in rats. We have found that
      gastric-projecting neurons of the dorsal vagal complex express apelin receptors
      (APJ), which mediate the inhibitory actions of apelin-13. The inhibitory effects
      of apelin were abolished by systemic preadministration of atropine, but not nitro
      l-arginine methyl ester (l-NAME). Apelin seems to modulate gastric motility via
      withdrawal of the tonically active vagal cholinergic pathway.

PMID- 29025732
TI  - Rack1 maintains intestinal homeostasis by protecting the integrity of the
      epithelial barrier.
AB  - Previously, we generated mouse models of Rack1 deficiency to identify key
      functions for Rack1 in regulating growth of intestinal epithelia: suppressing
      crypt cell proliferation and regeneration, promoting differentiation and
      apoptosis, and repressing development of neoplasia. However, other than low body
      weight, we did not detect an overt phenotype in mice constitutively deleted of
      Rack1 in intestinal epithelia ( vil-Cre: Rack1fl/fl mice), presumably because
      Rack1 was deleted in <10% of the total surface area of the epithelia. To assess
      the effect of Rack1 loss throughout the entire intestinal epithelia, we generated
      another mouse model of Rack1 deficiency, vil-Cre-ERT2: Rack1fl/fl. Within 5-10
      days of the initial tamoxifen treatment, the mice lost over 20% of their body
      weight, developed severe diarrhea that for some was bloody, became critically
      ill, and died, if not euthanized. Necropsies revealed mildly distended, fluid-,
      gas-, and sometimes blood-filled loops of small and large bowel, inguinal
      lymphadenopathy, and thrombocytosis. Rack1 was deleted in nearly 100% of the
      epithelia in both the small intestine and colon when assessed by
      immunofluorescent or immunoblot analyses. Rack1 expression in other tissues and
      organs was not different than in control mice, indicating tissue specificity of
      the recombination. Histopathology revealed a patchy, erosive, hemorrhagic,
      inflammatory enterocolitis with denuded, sloughed off surface epithelium, and
      crypt hyperplasia. These results suggest a protective function for Rack1 in
      maintaining the integrity of intestinal epithelia and for survival. NEW &
      NOTEWORTHY Our findings reveal a novel function for Rack1 in maintaining
      intestinal homeostasis by protecting the epithelial barrier. Rack1 loss results
      in a patchy, erosive, hemorrhagic, inflammatory enterocolitis, which resembles
      that of inflammatory bowel diseases (IBD) in humans. Understanding mechanisms
      that protect barrier function in normal intestine and how loss of that protection
      contributes to the pathogenesis of IBD could lead to improved therapies for these
      and other erosive diseases of the gastrointestinal tract.

PMID- 29025731
TI  - Macrophage depletion using clodronate liposomes decreases tumorigenesis and
      alters gut microbiota in the AOM/DSS mouse model of colon cancer.
AB  - We examined the role of macrophages in inflammation associated with colorectal
      cancer (CRC). Given the emerging evidence on immune-microbiota interactions in
      CRC, we also sought to examine the interaction between macrophages and gut
      microbiota. To induce CRC, male C57BL/6 mice ( n = 32) received a single
      injection of azoxymethane (AOM), followed by three cycles of dextran sodium
      sulfate (DSS)-supplemented water in weeks 1, 4, and 7. Prior to the final DSS
      cycle ( week 7) and twice weekly until euthanasia, mice ( n = 16/group) received
      either 200 MUl ip of clodronate-filled liposomes (CLD) or phosphate-buffered
      saline (PBS) encapsulated liposomes to deplete macrophages. Colon tissue was
      analyzed for polyp burden, macrophage markers, transcription factors, and
      inflammatory mediators. Stool samples were collected, and DNA was isolated and
      subsequently sequenced for 16S rRNA. Clodronate liposomes decreased tumor number
      by ~36% and specifically large (>=1 mm) tumors by ~36% ( P < 0.05). This was
      consistent with a decrease in gene expression of EMR1 in the colon tissue and
      polyp tissue as well as expression of select markers associated with M1 (IL-6)
      and M2 macrophages (IL-13, IL-10, TGFbeta, CCL17) in the colon tissue ( P <
      0.05). Similarly, there was a decrease in STAT3 and p38 MAPK and ERK signaling in
      colon tissue. Clodronate liposomes increased the relative abundance of the
      Firmicutes phylum ( P < 0.05) and specifically Lactobacillaceae and
      Clostridiaceae families, which have been associated with reduced CRC risk.
      Overall, these data support the development of therapeutic strategies to target
      macrophages in CRC and provide support for further evaluation of immune
      microbiota interactions in CRC. NEW & NOTEWORTHY We found that macrophage
      depletion during late-stage tumorigenesis is effective at reducing tumor growth.
      This was associated with a decrease in macrophage markers and chemokines in the
      colon tissue and a decrease in transcription factors that are linked to
      colorectal cancer. The macrophage-depleted group was found to have an increased
      abundance of Firmicutes, a phylum with documented anti-tumorigenic effects.
      Overall, these data support the development of therapeutic strategies to target
      macrophages in colorectal cancer.

PMID- 29025733
TI  - Hydrogen sulfide: an agent of stability at the microbiome-mucosa interface.
AB  - A diverse range of effects of the intestinal microbiota on mucosal defense and
      injury has become increasingly clear over the past decade. Hydrogen sulfide (H2S)
      has emerged as an important mediator of many physiological functions, including
      gastrointestinal mucosal defense and repair. Hydrogen sulfide is produced by
      gastrointestinal tract tissues and by bacteria residing within the gut and can
      influence the function of a wide range of cells. The microbiota also appears to
      be an important target of hydrogen sulfide. H2S donors can modify the gut
      microbiota, and the gastrointestinal epithelium is a major site of oxidation of
      microbial-derived H2S. When administered together with nonsteroidal anti
      inflammatory drugs, H2S can prevent some of the dysbiosis those drugs induce,
      possibly contributing to the observed prevention of gastrointestinal damage.
      Exogenous H2S can also markedly reduce the severity of experimental colitis and
      plays important roles in modulating epithelial cell-mucus-bacterial interactions
      in the intestine, contributing to its ability to promote resolution of
      inflammation and repair of tissue injury. In this paper we review recent studies
      examining the roles of H2S in mucosal defense, the possibility that H2S can
      damage the gastrointestinal epithelium, and effects of H2S on the gut microbiota
      and on mucus and biofilm interactions in the context of intestinal inflammation.

PMID- 29025735
TI  - Which pain medications are effective for sciatica (radicular leg pain)?

PMID- 29025736
TI  - Five minutes with . . . Mel Calvert.

PMID- 29025734
TI  - Dietary copper-fructose interactions alter gut microbial activity in male rats.
AB  - Dietary copper-fructose interactions contribute to the development of
      nonalcoholic fatty liver disease (NAFLD). Gut microbiota play critical roles in
      the pathogenesis of NAFLD. The aim of this study was to determine the effect of
      different dietary doses of copper and their interactions with high fructose on
      gut microbiome. Male weanling Sprague-Dawley rats were fed diets with adequate
      copper (6 ppm CuA), marginal copper (1.5 ppm CuM) (low copper), or supplemented
      copper (20 ppm CuS) (high copper) for 4 wk. Deionized water or deionized water
      containing 30% fructose (wt/vol) was given ad libitum. Copper status, liver
      enzymes, gut barrier function, and gut microbiome were evaluated. Both low- and
      high-copper diets led to liver injury in high-fructose-fed rats, and this was
      associated with gut barrier dysfunction, as shown by the markedly decreased tight
      junction proteins and increased gut permeability. 16S rDNA sequencing analysis
      revealed distinct alterations of the gut microbiome associated with dietary low-
      and high-copper/high-fructose feeding. The common features of the alterations of
      the gut microbiome were the increased abundance of Firmicutes and the depletion
      of Akkermansia. However, they differed mainly within the phylum Firmicutes. Our
      data demonstrated that a complex interplay among host, microbes, and dietary
      copper-fructose interaction regulates gut microbial metabolic activity, which may
      contribute to the development of liver injury and hepatic steatosis. The distinct
      alterations of gut microbial activity, which were associated with the different
      dietary doses of copper and fructose, imply that separate mechanism(s) may be
      involved. NEW & NOTEWORTHY First, dietary low- and high-copper/high-fructose
      induced liver injury are associated with distinct alterations of gut microbiome.
      Second, dietary copper level plays a critical role in maintaining the gut barrier
      integrity, likely by acting on the intestinal tight junction proteins and the
      protective commensal bacteria Akkermansia. Third, the alterations of gut
      microbiome induced by dietary low and high copper with or without fructose differ
      mainly within the phylum Firmicutes.

PMID- 29025737
TI  - Use of hospital-related health care among Health Links enrollees in the Central
      Ontario health region: a propensity-matched difference-in-differences study.
AB  - BACKGROUND: Health Links are a new model of providing care coordination for high
      cost, high-needs patients in Ontario. We evaluated use of hospital-related health
      care services among Health Links patients in the Central Local Health Integration
      Network (LHIN) of Ontario in the year before versus after program enrolment and
      compared rates of use with those among similar patients with complex needs not
      enrolled in the program (comparator group). METHODS: We identified all patients
      who received a Health Links coordinated care plan before Jan. 1, 2015, using
      linked registry and health administrative data. We used propensity scores to
      match (1:1) enrollees (registry) with comparator patients (administrative data).
      Using a difference-in-differences approach with generalized estimating equations,
      we evaluated 5 measures of Health Link performance: rates of hospital admission,
      emergency department visits, days in acute care, 30-day readmissions and 7-day
      postdischarge primary care follow-up. RESULTS: Of the 344 enrollees in the
      registry, we matched 313 [91.0%] to comparator patients. All measured
      sociodemographic, comorbidity and health care use characteristics were balanced
      between the 2 groups (all standardized differences < 0.10). For enrollees, the
      rate of days in acute care per person-year increased by 35% (incidence rate ratio
      1.35 [confidence interval 1.11-1.65]) after versus before the index date, but
      differences were nonsignificant for all other measures. Difference-in-differences
      analyses revealed greater reductions in hospital admissions, emergency department
      visits and acute care days after the index date in the comparator group than
      among enrollees. INTERPRETATION: Initial implementation of the Health Link
      program in the Central LHIN did not reduce selected indicators of Health Link
      performance among enrollees. As the Health Link program evolves and
      standardization is implemented, future research may reveal effects from the
      initiative in other outcomes or with longer follow-up.

PMID- 29025739
TI  - Government promises "ambitious" science deal with EU.

PMID- 29025738
TI  - Local, local, local: the regeneration project that puts the community in charge
      of its health.

PMID- 29025741
TI  - NHS aims to expand emergency department workforce to combat pressures.

PMID- 29025740
TI  - FCR achieves long-term durable remissions in patients with IGHV-mutated CLL.
AB  - In chronic lymphocytic leukemia (CLL) patients with mutated IGHV, 3 recent
      studies have demonstrated prolonged progression-free survival (PFS) after
      treatment with fludarabine-cyclophosphamide-rituximab (FCR) chemoimmunotherapy.
      We performed a systematic review to assess the benefit of FCR for patients with
      CLL and identified 5 randomized trials that met our inclusion criteria. FCR
      improved complete remission, PFS and overall survival vs the comparator; median
      PFS was not reached in the subgroup of CLL patients with mutated IGHV.

PMID- 29025742
TI  - GPs indemnity to be provided through state backed scheme, says Hunt.

PMID- 29025743
TI  - Acute constipation and vomiting with the "coffee bean" sign.

PMID- 29025744
TI  - Four study design principles for genetic investigations using next generation
      sequencing.

PMID- 29025745
TI  - Association of Persistent, Incident, and Remittent Proteinuria With Stroke Risk
      in Patients With Diabetes Mellitus or Prediabetes Mellitus.
AB  - BACKGROUND: Proteinuria often changes dynamically, showing either regression or
      progression. The impact of changes in proteinuria on future stroke risk remains
      largely unknown. We hypothesized that changes in proteinuria would be associated
      with stroke risk in patients with diabetes mellitus and prediabetes mellitus.
      METHODS AND RESULTS: The study population included 17 380 participants with
      diabetes mellitus or prediabetes mellitus enrolled in a prospective Chinese
      cohort. From the baseline and 2-year dipstick screening results, participants
      were classified as having no proteinuria or remittent, incident, or persistent
      proteinuria. Reduction in proteinuria was calculated as the baseline minus 2-year
      proteinuria. Stroke outcomes were assessed in subsequent follow-ups. Data were
      analyzed using Cox proportional-hazards models. During a median follow-up of 6.9
      years, we identified 751 patients with stroke. Stroke risk was increased for
      participants with persistent (hazard ratio [HR], 1.64; 95% confidence interval
      [CI], 1.18-2.30), incident (HR, 1.52; 95% CI, 1.22-1.89), and remittent (HR,
      1.42; 95% CI, 1.01-2.02) proteinuria compared with those with no proteinuria.
      Persistent proteinuria was associated with a higher risk of stroke for
      participants with prediabetes mellitus (HR, 2.58; 95% CI, 1.58-4.22) compared
      with those with diabetes mellitus (HR, 1.35; 95% CI, 0.86-2.12 [P for
      interaction=0.0083]). Proteinuria reduction contributed to a decrease in stroke
      incidence (HR, 0.88; 95% CI, 0.81-0.95). The results were confirmed by
      sensitivity analyses. CONCLUSIONS: Persistent, incident, and remittent
      proteinuria are independent indicators of stroke risk in both diabetic and
      prediabetic populations.

PMID- 29025746
TI  - Clinical Prediction Model for Time in Therapeutic Range While on Warfarin in
      Newly Diagnosed Atrial Fibrillation.
AB  - BACKGROUND: Though warfarin has historically been the primary oral anticoagulant
      for stroke prevention in newly diagnosed atrial fibrillation (AF), several new
      direct oral anticoagulants may be preferred when anticoagulation control with
      warfarin is expected to be poor. This study developed a prediction model for time
      in therapeutic range (TTR) among newly diagnosed AF patients on newly initiated
      warfarin as a tool to assist decision making between warfarin and direct oral
      anticoagulants. METHODS AND RESULTS: This electronic medical record-based,
      retrospective study included newly diagnosed, nonvalvular AF patients with no
      recent warfarin exposure receiving primary care services through a large
      healthcare system in rural Pennsylvania. TTR was estimated as the percentage of
      time international normalized ratio measurements were between 2.0 and 3.0 during
      the first year following warfarin initiation. Candidate predictors of TTR were
      chosen from data elements collected during usual clinical care. A TTR prediction
      model was developed and temporally validated and its predictive performance was
      compared with the SAMe-TT2R2 score (sex, age, medical history, treatment,
      tobacco, race) using R2 and c-statistics. A total of 7877 newly diagnosed AF
      patients met study inclusion criteria. Median (interquartile range) TTR within
      the first year of starting warfarin was 51% (32, 67). Of 85 candidate predictors
      evaluated, 15 were included in the final validated model with an R2 of 15.4%. The
      proposed model showed better predictive performance than the SAMe-TT2R2 score
      (R2=3.0%). CONCLUSIONS: The proposed prediction model may assist decision making
      on the proper mode of oral anticoagulant among newly diagnosed AF patients.
      However, predicting TTR on warfarin remains challenging.

PMID- 29025747
TI  - Uncoupling Protein 2 Inhibits Myointimal Hyperplasia in Preclinical Animal Models
      of Vascular Injury.
AB  - BACKGROUND: Intracoronary stent restenosis, characterized by excessive smooth
      muscle cell (SMC) proliferation and myointimal hyperplasia, remains a clinical
      challenge. Mitochondrial membrane potential has been linked to the proliferative
      rate of SMCs. This study aimed to screen a critical gene regulating mitochondrial
      potential and to confirm its effects on myointimal formation in preclinical
      animal models. METHODS AND RESULTS: We performed transcriptome screening for
      genes differentially expressed in ligated versus unligated mouse carotid
      arteries. We observed that uncoupling protein 2 gene (Ucp2) mRNA, encoding UCP2,
      was transiently upregulated during the first 3 days after ligation and then
      significantly downregulated from day 7 through day 21, during which time
      neointima formed remarkably. The UCP2 protein level also declined after day 7 of
      ligation. In ligated carotid arteries, Ucp2-/- mice, compared with wild-type
      littermates, exhibited accelerated myointimal formation, which was associated
      with increased superoxide production and can be attenuated by treatment with
      antioxidant 4-hydroxy-2,2,6,6-tetramethyl-piperidinoxyl (TEMPOL). Knockdown of
      UCP2 enhanced human aortic SMC migration and proliferation that can also be
      attenuated by TEMPOL, whereas UCP2 overexpression inhibited SMC migration and
      proliferation, along with decreased activity of nuclear factor-kappaB. Moreover,
      nuclear factor-kappaB inhibitor attenuated UCP2 knockdown-enhanced SMC
      proliferation. Adenovirus-mediated overexpression of UCP2 inhibited myointimal
      formation in balloon-injured carotid arteries of rats and rabbits and in-stent
      stenosis of porcine coronary arteries. Moreover, UCP2 overexpression also
      suppressed neointimal hyperplasia in cultured human saphenous vein ex vivo.
      CONCLUSIONS: UCP2 inhibits myointimal hyperplasia after vascular injury, probably
      through suppressing nuclear factor-kappaB-dependent SMC proliferation and
      migration, rendering UCP2 a potential therapeutic target against restenosis.

PMID- 29025751
TI  - Meet the First Authors.

PMID- 29025748
TI  - Compromised Cerebrovascular Regulation and Cerebral Oxygenation in Pulmonary
      Arterial Hypertension.
AB  - BACKGROUND: Functional cerebrovascular regulatory mechanisms are important for
      maintaining constant cerebral blood flow and oxygen supply in heathy individuals
      and are altered in heart failure. We aim to examine whether pulmonary arterial
      hypertension (PAH) is associated with abnormal cerebrovascular regulation and
      lower cerebral oxygenation and their physiological and clinical consequences.
      METHODS AND RESULTS: Resting mean flow velocity in the middle cerebral artery
      mean flow velocity in the middle cerebral artery (MCAvmean); transcranial
      Doppler), cerebral pressure-flow relationship (assessed at rest and during squat
      stand maneuvers; analyzed using transfer function analysis), cerebrovascular
      reactivity to CO2, and central chemoreflex were assessed in 11 patients with PAH
      and 11 matched healthy controls. Both groups also completed an incremental ramp
      exercise protocol until exhaustion, during which MCAvmean, mean arterial
      pressure, cardiac output (photoplethysmography), end-tidal partial pressure of
      CO2, and cerebral oxygenation (near-infrared spectroscopy) were measured.
      Patients were characterized by a significant decrease in resting MCAvmean
      (P<0.01) and higher transfer function gain at rest and during squat-stand
      maneuvers (both P<0.05). Cerebrovascular reactivity to CO2 was reduced (P=0.03),
      whereas central chemoreceptor sensitivity was increased in PAH (P<0.01), the
      latter correlating with increased resting ventilation (R2=0.47; P<0.05) and the
      exercise ventilation/CO2 production slope (VE/VCO2 slope; R2=0.62; P<0.05) during
      exercise for patients. Exercise-induced increases in MCAvmean were limited in PAH
      (P<0.05). Reduced MCAvmean contributed to impaired cerebral oxygen delivery and
      oxygenation (both P<0.05), the latter correlating with exercise capacity in
      patients with PAH (R2=0.52; P=0.01). CONCLUSIONS: These findings provide
      comprehensive evidence for physiologically and clinically relevant impairments in
      cerebral hemodynamic regulation and oxygenation in PAH.

PMID- 29025749
TI  - Late Onset Postcapillary Pulmonary Hypertension in Patients With Transposition of
      the Great Arteries and Mustard or Senning Baffles.
AB  - BACKGROUND: There is a paucity of data regarding late-onset pulmonary
      hypertension (PH) in patients with transposition of the great arteries and atrial
      switch surgery. METHODS AND RESULTS: A retrospective cohort study was conducted
      on 140 adults with transposition of the great arteries and atrial switch surgery,
      age 37.3+/-7.8, 37.1% female, in order to assess the prevalence and
      characteristics of late-onset PH and explore associated factors. Patients were
      followed for a median of 32.3 years after atrial switch surgery and 10.0 years
      after their first referral visit. PH was detected in 18 of 33 (54.5%) patients
      who had invasive hemodynamic studies. Average age at diagnosis of PH was 33.9+/
      8.1 years. PH was postcapillary in all, with a mean pulmonary artery pressure of
      36+/-12 mm Hg and mean pulmonary capillary wedge pressure of 28+/-8 mm Hg. PH was
      diagnosed in 13 of 17 (76.5%) patients who had cardiac catheterization for heart
      failure or decreased exercise tolerance. In multivariable analyses, systemic
      hypertension (odds ratio 9.4, 95% confidence interval 2.2-39.4, P=0.002) and
      heart failure or New York Heart Association class III or IV symptoms (odds ratio
      49.8, 95% confidence interval 8.6-289.0, P<0.001) were independently associated
      with PH. Patients with PH were more likely to develop cardiovascular
      comorbidities including atrial (P=0.001) and ventricular (P=0.008) arrhythmias,
      require hospitalizations for heart failure (P<0.001), and undergo tricuspid valve
      surgery (P<0.001). Mortality was significantly higher in patients with PH (hazard
      ratio 9.4, 95% confidence interval 2.1-43.0], P<0.001). CONCLUSIONS: Late-onset
      postcapillary PH is highly prevalent in adults with transposition of the great
      arteries and atrial switch surgery and is associated with an adverse prognosis.

PMID- 29025750
TI  - Fludrocortisone Is Associated With a Higher Risk of All-Cause Hospitalizations
      Compared With Midodrine in Patients With Orthostatic Hypotension.
AB  - BACKGROUND: Orthostatic hypotension causes ~80 000 hospitalizations per year in
      the United States. Treatments for orthostatic hypotension include
      fludrocortisone, a mineralocorticoid analog that promotes sodium reabsorption;
      and midodrine, an alpha-1 adrenergic agonist that is a direct vasoconstrictor.
      Although both medications are used to treat orthostatic hypotension, few studies
      have compared their relative safety. METHODS AND RESULTS: We compared incidence
      rates of hospitalizations for all causes, and for congestive heart failure
      between users of fludrocortisone and users of midodrine in a retrospective cohort
      study of Tennessee Medicaid adult enrollees (1995-2009). Adjusted incidence rate
      ratios were calculated using negative binomial regression models. Subgroup
      analyses based on history of congestive heart failure were conducted. We studied
      1324 patients initiating fludrocortisone and 797 patients initiating midodrine.
      Compared with fludrocortisone users, midodrine users had higher prevalence of
      cardiovascular conditions. Incidence rates of all-cause hospitalizations for
      fludrocortisone and midodrine users were 1489 and 1330 per 1000 person-years,
      respectively (adjusted incidence-rate ratio 1.20, 95% confidence interval, 1.02
      1.40). The respective rates of heart failure-related hospitalization were 76 and
      84 per 1000 person-years (adjusted incidence-rate ratio: 1.33, 95% confidence
      interval, 0.79-2.56). Among patients with a history of congestive heart failure,
      the rates of all-cause hospitalization for fludrocortisone and midodrine were
      2448 and 1820 per 1000 person-years (adjusted incidence-rate ratio: 1.42, 95%
      confidence interval, 1.07-1.90), and the respective rates of heart failure
      exacerbation-related hospitalizations were 297 and 263 per 1000 person-years
      (adjusted incidence-rate ratio: 1.48, 95% confidence interval, 0.69-3.16).
      CONCLUSIONS: Compared with users of midodrine, users of fludrocortisone had
      higher rates of all-cause hospitalizations, especially among patients with
      congestive heart failure.

PMID- 29025752
TI  - Liver Kinase B1 Links Macrophage Metabolism Sensing and Atherosclerosis.

PMID- 29025753
TI  - Novel Pathways for Regulation of Sinoatrial Node Plasticity and Heart Rate.

PMID- 29025755
TI  - Cardiovascular Risk Prediction: Widening the Net.

PMID- 29025754
TI  - Unfriendly Fire From Neutrophils Promiscuously Potentiates Cardiovascular
      Inflammation.

PMID- 29025756
TI  - Elena Matsa: Lighting Fires for Heart Disease.

PMID- 29025757
TI  - Current State of Basic and Translational Cardiovascular Research in Spain.

PMID- 29025758
TI  - General Overview of the 14th International Symposium on Stem Cell Therapy and
      Cardiovascular Innovations: Working Progress of a Global Initiative in 2017.

PMID- 29025759
TI  - Paracrine-Mediated Systemic Anti-Inflammatory Activity of Intravenously
      Administered Mesenchymal Stem Cells: A Transformative Strategy for Cardiac Stem
      Cell Therapeutics.

PMID- 29025762
TI  - Modifying Mendel Redux: Unbiased Approaches Can Find Modifiers.

PMID- 29025760
TI  - Prediction for Intravenous Immunoglobulin Resistance by Using Weighted Genetic
      Risk Score Identified From Genome-Wide Association Study in Kawasaki Disease.
AB  - BACKGROUND: Intravenous immunoglobulin (IVIG) is the treatment of choice in
      Kawasaki disease (KD). IVIG is used to prevent cardiovascular complications
      related to KD. However, a proportion of KD patients have persistent fever after
      IVIG treatment and are defined as IVIG resistant. METHODS AND RESULTS: To develop
      a risk scoring system based on genetic markers to predict IVIG responsiveness in
      KD patients, a total of 150 KD patients (126 IVIG responders and 24 IVIG
      nonresponders) were recruited for this study. A genome-wide association analysis
      was performed to compare the 2 groups and identified risk alleles for IVIG
      resistance. A weighted genetic risk score was calculated by the natural log of
      the odds ratio multiplied by the number of risk alleles. Eleven single-nucleotide
      polymorphisms were identified by genome-wide association study. The KD patients
      were categorized into 3 groups based on their calculated weighted genetic risk
      score. Results indicated a significant association between weighted genetic risk
      score (groups 3 and 4 versus group 1) and the response to IVIG (Fisher's exact P
      value 4.518*10-03 and 8.224*10-10, respectively). CONCLUSIONS: This is the first
      weighted genetic risk score study based on a genome-wide association study in KD.
      The predictive model integrated the additive effects of all 11 single-nucleotide
      polymorphisms to provide a prediction of the responsiveness to IVIG.

PMID- 29025763
TI  - One Size Does Not Fit All: Genetic Prediction of Kawasaki Disease Treatment
      Response in Diverse Populations.

PMID- 29025764
TI  - Higher Risk of Vascular Dementia in Myocardial Infarction Survivors.
AB  - BACKGROUND: Increased risk of dementia after myocardial infarction (MI) may be
      mediated by shared risk factors (eg, atherosclerosis) and post-MI stroke. We
      examined risk of dementia in 1-year survivors of MI. METHODS: Using Danish
      medical registries, we conducted a nationwide population-based cohort study of
      all patients with first-time MI and a sex-, birth year-, and calendar year
      matched general population comparison cohort without MI (1980-2012). Cox
      regression analysis was used to compute 1- to 35-year adjusted hazard ratios
      (aHRs) for dementia, controlled for matching factors and adjusted for
      comorbidities and socioeconomic status. RESULTS: We identified 314 911 patients
      with MI and 1 573 193 matched comparison cohort members randomly sampled from the
      general population (median age, 70 years; 63% male). After 35 years of follow-up,
      the cumulative incidence of all-cause dementia in the MI cohort was 9% (2.8% for
      Alzheimer disease, 1.6% for vascular dementia, and 4.5% for other dementias).
      Compared with the general population cohort, MI was not associated with all-cause
      dementia (aHR, 1.01; 95% confidence interval [CI], 0.98-1.03). Risk of Alzheimer
      disease (aHR, 0.92; 95% CI, 0.88-0.95) and other dementias (aHR, 0.98; 95% CI,
      0.95-1.01) also approximated unity. However, MI was associated with higher risk
      of vascular dementia (aHR, 1.35; 95% CI, 1.28-1.43), which was substantially
      strengthened for patients experiencing stroke after MI (aHR, 4.48; 95% CI, 3.29
      6.12). CONCLUSIONS: MI was associated with higher risk of vascular dementia
      throughout follow-up, and this association was stronger in patients with stroke.
      The risk of Alzheimer disease and other dementias was not higher in patients with
      MI.

PMID- 29025765
TI  - Long-Term Potassium Monitoring and Dynamics in Heart Failure and Risk of
      Mortality.
AB  - BACKGROUND: The prognostic value of long-term potassium monitoring and dynamics
      in heart failure has not been characterized completely. We sought to determine
      the association between serum potassium values collected at follow-up with all
      cause mortality in a prospective and consecutive cohort of patients discharged
      from a previous acute heart failure admission. METHODS: Serum potassium was
      measured at every physician-patient encounter, including hospital admissions and
      ambulatory settings. The multivariable-adjusted association of serum potassium
      with mortality was assessed by using comprehensive state-of-the-art regression
      methods that can accommodate time-dependent exposure modeling. RESULTS: The study
      sample included 2164 patients with a total of 16 116 potassium observations. Mean
      potassium at discharge was 4.3+/-0.48 mEq/L. Hypokalemia (<3.5 mEq/L),
      normokalemia (3.5-5.0 mEq/L), and hyperkalemia (>5 mEq/L) were observed at the
      index admission in 77 (3.6%), 1965 (90.8%), and 122 (5.6%) patients,
      respectively. At a median follow-up of 2.8 years (range, 0.03-12.8 years), 1090
      patients died (50.4%). On a continuous scale, the multivariable-adjusted
      association of potassium values and mortality revealed a nonlinear association (U
      shaped) with higher risk at both ends of its distribution (omnibus P=0.001).
      Likewise, the adjusted hazard ratios for hypokalemia and hyperkalemia,
      normokalemia as reference, were 2.35 (95% confidence interval, 1.40-3.93;
      P=0.001) and 1.55 (95% confidence interval, 1.11-2.16; P=0.011), respectively
      (omnibus P=0.0003). Furthermore, dynamic changes in potassium were independently
      associated with substantial differences in mortality risk. Potassium
      normalization was independently associated with lower mortality risk (P=0.001).
      CONCLUSIONS: Either modeled continuously or categorically, serum potassium levels
      during long-term monitoring were independently associated with mortality in
      patients with heart failure. Likewise, persistence of abnormal potassium levels
      was linked to a higher risk of death in comparison with patients who maintained
      or returned to normal values.

PMID- 29025761
TI  - Genome-Wide Association Study to Find Modifiers for Tetralogy of Fallot in the
      22q11.2 Deletion Syndrome Identifies Variants in the GPR98 Locus on 5q14.3.
AB  - BACKGROUND: The 22q11.2 deletion syndrome (22q11.2DS; DiGeorge
      syndrome/velocardiofacial syndrome) occurs in 1 of 4000 live births, and 60% to
      70% of affected individuals have congenital heart disease, ranging from mild to
      severe. In our cohort of 1472 subjects with 22q11.2DS, a total of 62% (n=906)
      have congenital heart disease and 36% (n=326) of these have tetralogy of Fallot
      (TOF), comprising the largest subset of severe congenital heart disease in the
      cohort. METHODS AND RESULTS: To identify common genetic variants associated with
      TOF in individuals with 22q11.2DS, we performed a genome-wide association study
      using Affymetrix 6.0 array and imputed genotype data. In our cohort, TOF was
      significantly associated with a genotyped single-nucleotide polymorphism
      (rs12519770, P=2.98*10-8) in an intron of the adhesion GPR98 (G-protein-coupled
      receptor V1) gene on chromosome 5q14.3. There was also suggestive evidence of
      association between TOF and several additional single-nucleotide polymorphisms in
      this region. Some genome-wide significant loci in introns or noncoding regions
      could affect regulation of genes nearby or at a distance. On the basis of this
      possibility, we examined existing Hi-C chromatin conformation data to identify
      genes that might be under shared transcriptional regulation within the region on
      5q14.3. There are 6 genes in a topologically associated domain of chromatin with
      GPR98, including MEF2C (Myocyte-specific enhancer factor 2C). MEF2C is the only
      gene that is known to affect heart development in mammals and might be of
      interest with respect to 22q11.2DS. CONCLUSIONS: In conclusion, common variants
      may contribute to TOF in 22q11.2DS and may function in cardiac outflow tract
      development.

PMID- 29025769
TI  - Low Adrenomedullin and Endothelin-1 Predict Cardioinhibitory Response During
      Vasovagal Reflex in Adults Over 40 Years of Age.

PMID- 29025766
TI  - CAR T Therapy Targeting ICAM-1 Eliminates Advanced Human Thyroid Tumors.
AB  - Purpose: Poorly differentiated thyroid cancer and anaplastic thyroid cancer (ATC)
      are rare yet lethal malignancies with limited treatment options. Many malignant
      tumors, including papillary thyroid cancer (PTC) and ATC, are associated with
      increased expression of ICAM-1, providing a rationale for utilizing ICAM-1
      targeting agents for the treatment of aggressive cancer. We developed a third
      generation chimeric antigen receptor (CAR) targeting ICAM-1 to leverage adoptive
      T-cell therapy as a new treatment modality.Experimental Design: ICAM-1 CAR T
      cells were applied to multiple malignant and nonmalignant target cells to
      investigate specific target cell death and "off-tumor" toxicity in vitroIn vivo
      therapeutic efficacy of ICAM-1 CAR T cells was examined in ATC mouse models
      established from a cell line and patient-derived tumors that rapidly develop
      systemic metastases.Results: ICAM-1 CAR T cells demonstrated robust and specific
      killing of PTC and ATC cell lines in vitro Interestingly, although certain ATC
      cell lines showed heterogeneous levels of ICAM-1 expression, addition of
      cytotoxic CAR T cells induced increased ICAM-1 expression such that all cell
      lines became targetable. In mice with systemic ATC, a single administration of
      ICAM-1 CAR T cells mediated profound tumor killing that resulted in long-term
      remission and significantly improved survival. Patient-derived ATC cells
      overexpressed ICAM-1 and were largely eliminated by autologous ICAM-1 CAR T cells
      in vitro and in animal models.Conclusions: Our findings are the first
      demonstration of CAR T therapy against both a metastatic, thyroid cancer cell
      line and advanced ATC patient-derived tumors that exhibit dramatic therapeutic
      efficacy and survival benefit in animal studies. Clin Cancer Res; 23(24); 7569
      83. (c)2017 AACR.

PMID- 29025770
TI  - Cl-/HCO3- Exchanger slc26a6: A pH Regulator Shapes the Cardiac Action Potential.

PMID- 29025767
TI  - Monocytes and Granulocytes Reduce CD38 Expression Levels on Myeloma Cells in
      Patients Treated with Daratumumab.
AB  - Purpose: Daratumumab treatment results in a marked reduction of CD38 expression
      on multiple myeloma cells. The aim of this study was to investigate the clinical
      implications and the underlying mechanisms of daratumumab-mediated CD38
      reduction.Experimental Design: We evaluated the effect of daratumumab alone or in
      combination with lenalidomide-dexamethasone, on CD38 levels of multiple myeloma
      cells and nontumor immune cells in the GEN501 study (daratumumab monotherapy) and
      the GEN503 study (daratumumab combined with lenalidomide-dexamethasone). In vitro
      assays were also performed.Results: In both trials, daratumumab reduced CD38
      expression on multiple myeloma cells within hours after starting the first
      infusion, regardless of depth and duration of the response. In addition, CD38
      expression on nontumor immune cells, including natural killer cells, T cells, B
      cells, and monocytes, was also reduced irrespective of alterations in their
      absolute numbers during therapy. In-depth analyses revealed that CD38 levels of
      multiple myeloma cells were only reduced in the presence of complement or
      effector cells, suggesting that the rapid elimination of CD38high multiple
      myeloma cells can contribute to CD38 reduction. In addition, we discovered that
      daratumumab-CD38 complexes and accompanying cell membrane were actively
      transferred from multiple myeloma cells to monocytes and granulocytes. This
      process of trogocytosis was also associated with reduced surface levels of some
      other membrane proteins, including CD49d, CD56, and CD138.Conclusions:
      Daratumumab rapidly reduced CD38 expression levels, at least in part, through
      trogocytosis. Importantly, all these effects also occurred in patients with deep
      and durable responses, thus excluding CD38 reduction alone as a mechanism of
      daratumumab resistance.The trials were registered at www.clinicaltrials.gov as
      NCT00574288 (GEN501) and NCT1615029 (GEN503). Clin Cancer Res; 23(24); 7498-511.
      (c)2017 AACR.

PMID- 29025768
TI  - Action Potential Shortening and Impairment of Cardiac Function by Ablation of
      Slc26a6.
AB  - BACKGROUND: Intracellular pH (pHi) is critical to cardiac excitation and
      contraction; uncompensated changes in pHi impair cardiac function and trigger
      arrhythmia. Several ion transporters participate in cardiac pHi regulation. Our
      previous studies identified several isoforms of a solute carrier Slc26a6 to be
      highly expressed in cardiomyocytes. We show that Slc26a6 mediates electrogenic Cl
      /HCO3- exchange activities in cardiomyocytes, suggesting the potential role of
      Slc26a6 in regulation of not only pHi, but also cardiac excitability. METHODS AND
      RESULTS: To test the mechanistic role of Slc26a6 in the heart, we took advantage
      of Slc26a6 knockout (Slc26a6-/- ) mice using both in vivo and in vitro analyses.
      Consistent with our prediction of its electrogenic activities, ablation of
      Slc26a6 results in action potential shortening. There are reduced Ca2+ transient
      and sarcoplasmic reticulum Ca2+ load, together with decreased sarcomere
      shortening in Slc26a6-/- cardiomyocytes. These abnormalities translate into
      reduced fractional shortening and cardiac contractility at the in vivo level.
      Additionally, pHi is elevated in Slc26a6-/- cardiomyocytes with slower recovery
      kinetics from intracellular alkalization, consistent with the Cl-/HCO3- exchange
      activities of Slc26a6. Moreover, Slc26a6-/- mice show evidence of sinus
      bradycardia and fragmented QRS complex, supporting the critical role of Slc26a6
      in cardiac conduction system. CONCLUSIONS: Our study provides mechanistic
      insights into Slc26a6, a unique cardiac electrogenic Cl-/HCO3- transporter in
      ventricular myocytes, linking the critical roles of Slc26a6 in regulation of pHi,
      excitability, and contractility. pHi is a critical regulator of other membrane
      and contractile proteins. Future studies are needed to investigate possible
      changes in these proteins in Slc26a6-/- mice.

PMID- 29025771
TI  - Endothelial Activation and Blood-Brain Barrier Disruption in Neurotoxicity after
      Adoptive Immunotherapy with CD19 CAR-T Cells.
AB  - Lymphodepletion chemotherapy followed by infusion of CD19-targeted chimeric
      antigen receptor-modified T (CAR-T) cells can be complicated by neurologic
      adverse events (AE) in patients with refractory B-cell malignancies. In 133
      adults treated with CD19 CAR-T cells, we found that acute lymphoblastic leukemia,
      high CD19+ cells in bone marrow, high CAR-T cell dose, cytokine release syndrome,
      and preexisting neurologic comorbidities were associated with increased risk of
      neurologic AEs. Patients with severe neurotoxicity demonstrated evidence of
      endothelial activation, including disseminated intravascular coagulation,
      capillary leak, and increased blood-brain barrier (BBB) permeability. The
      permeable BBB failed to protect the cerebrospinal fluid from high concentrations
      of systemic cytokines, including IFNgamma, which induced brain vascular pericyte
      stress and their secretion of endothelium-activating cytokines. Endothelial
      activation and multifocal vascular disruption were found in the brain of a
      patient with fatal neurotoxicity. Biomarkers of endothelial activation were
      higher before treatment in patients who subsequently developed grade >=4
      neurotoxicity.Significance: We provide a detailed clinical, radiologic, and
      pathologic characterization of neurotoxicity after CD19 CAR-T cells, and identify
      risk factors for neurotoxicity. We show endothelial dysfunction and increased BBB
      permeability in neurotoxicity and find that patients with evidence of endothelial
      activation before lymphodepletion may be at increased risk of neurotoxicity.
      Cancer Discov; 7(12); 1404-19. (c)2017 AACR.See related commentary by Mackall and
      Miklos, p. 1371This article is highlighted in the In This Issue feature, p. 1355.

PMID- 29025773
TI  - Erdheim-Chester disease: atypical presentation of a rare disease.
AB  - We report the clinical case of an adult patient referred to our hospital because
      of trismus due to a tumour in the right infratemporal and pterygomaxillary fossa.
      He referred hyporexia, weight loss and right trigeminal neuralgia. On physical
      examination, he had trismus and diplopia. On neuroimaging, the tumour invaded the
      central nervous system affecting the right temporal lobe and orbit, and the
      sellar region. Tumour biopsy revealed foamy histiocytes and isolated giant
      multinuclear cells immunoreactive to CD68 and negative to CD1a and S100. A
      diagnosis of Erdheim-Chester disease was made. Non-evidence of large bone
      involvement was found in neither plain radiographs nor Technetium 99 m bone
      scintigraphy. BRAFV600E mutation analysis was negative. Because of raised
      intracranial pressure, a debulking surgery of the intracranial histiocytic
      process was performed. The patient improved his symptoms and remains clinically
      stable after 12 months of treatment with pegylated interferon-alpha-2a 180
      ug/weekly.

PMID- 29025774
TI  - Posterior fossa progressive multifocal leukoencephalopathy: first presentation of
      an unknown autoimmune disease.
AB  - We present a case of a 57-year-old man who presented with progressive cerebellar
      dysarthria and cerebellar ataxia. Additional investigations confirmed the
      diagnosis of progressive multifocal leukoencephalopathy (PML) in the posterior
      fossa. This is a demyelinating disease of the central nervous system, caused by
      an opportunistic infection with John Cunningham virus. PML has previously been
      considered a lethal condition, but because of careful monitoring of patients with
      HIV and of patients using immunosuppressive drugs it is discovered in earlier
      stages and prognosis can be improved. Our patient had no known immune
      compromising state, but further work-up revealed that the PML was most likely the
      first presentation of a previous untreated autoimmune disorder: sarcoidosis.

PMID- 29025775
TI  - A unique case of nephrogenic systemic fibrosis from gadolinium exposure in a
      patient with normal eGFR.
AB  - A 57-year-old woman presented with swelling and thickening of the skin of the
      lower extremities. Three months prior to presentation, patient had MRI with
      gadolinium as part of an evaluation for suspected pancreatic malignancy.
      Creatinine levels at the time of gadolinium exposure were 0.9-1.2 mg/dL, with a
      corresponding estimated glomerular filtration rate of 64 mL/min/1.73m2 by
      modification of diet in renal disease equation. Twenty-four-hour urine creatinine
      clearance was performed as an outpatient following development of symptoms. This
      revealed a creatinine clearance of 23 mL/min, suggestive of advanced chronic
      kidney disease despite an estimated glomerular filtration rate of 64
      mL/min/1.73m2 Skin biopsy was positive for sclerosing dermopathy. These findings,
      in addition to the temporal association with gadolinium exposure, led to the
      diagnosis of nephrogenic systemic fibrosis.

PMID- 29025772
TI  - Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of
      Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer.
AB  - Mechanisms of acquired resistance to immune checkpoint inhibitors (ICI) are
      poorly understood. We leveraged a collection of 14 ICI-resistant lung cancer
      samples to investigate whether alterations in genes encoding HLA Class I antigen
      processing and presentation machinery (APM) components or interferon signaling
      play a role in acquired resistance to PD-1 or PD-L1 antagonistic antibodies.
      Recurrent mutations or copy-number changes were not detected in our cohort. In
      one case, we found acquired homozygous loss of B2M that caused lack of cell
      surface HLA Class I expression in the tumor and a matched patient-derived
      xenograft (PDX). Downregulation of B2M was also found in two additional PDXs
      established from ICI-resistant tumors. CRISPR-mediated knockout of B2m in an
      immunocompetent lung cancer mouse model conferred resistance to PD-1 blockade in
      vivo, proving its role in resistance to ICIs. These results indicate that HLA
      Class I APM disruption can mediate escape from ICIs in lung cancer.Significance:
      As programmed death 1 axis inhibitors are becoming more established in standard
      treatment algorithms for diverse malignancies, acquired resistance to these
      therapies is increasingly being encountered. Here, we found that defective
      antigen processing and presentation can serve as a mechanism of such resistance
      in lung cancer. Cancer Discov; 7(12); 1420-35. (c)2017 AACR.This article is
      highlighted in the In This Issue feature, p. 1355.

PMID- 29025776
TI  - Unusual case of prosthetic joint infection caused by Francisella Tularensis.
AB  - Tularaemia is a zoonotic infection caused by Francisella
      tularensis.Ulceroglandular, glandular, oculoglandular, pharyngeal, typhoidal and
      pneumonic types are the different types of the disease. Infection of prosthetic
      joints occurs at an exceedingly uncommon rate. We report a case of prosthetic
      joint infection involving the hip with F. tularensis, which to the best of our
      knowledge after a thorough literature review is the second of its kind.

PMID- 29025777
TI  - Oesophageal ischaemia: an uncommon cause of chest pain.
AB  - A 79-year-old woman with a history of ischaemic heart disease and atrial
      fibrillation presented to hospital with severe chest pain. Blood tests showed an
      elevated D-dimer and a rise in troponin I. ECG showed right bundle branch block
      pattern and T wave inversion in leads V1 to V3, although these changes were
      present in old ECGs. A chest X-ray was done which was normal. Due to the nature
      and severity of her pain a CT aortic angiogram was done. This did not show any
      evidence of aortic dissection or a pulmonary embolism. The patient then had
      several episodes of haematemesis. An urgent oesophagogastroduodenoscopy was done
      which showed a circumferential, well demarcated area of blackened oesophageal
      mucosa. The patient was diagnosed with ischaemic damage to her oesophagus.

PMID- 29025778
TI  - Allergic bronchopulmonary mycosis presenting as a new lung mass.

PMID- 29025779
TI  - Scorpion bite-induced ischaemic stroke.
AB  - We report a 54-year-old woman with scorpion bite. After 3 hours of admission, the
      patient developed sudden onset tachycardia with hypotension. Cardiac evaluation
      showed raised creatine kinase MB isoenzyme was elevated; ECG and two-dimensional
      echocardiography findings were suggestive of myocarditis. Subsequently, she
      developed transient ventricular tachycardia before developing abrupt onset, right
      hemiplegia, global aphasia and progressive worsening of sensorium 12 hours after
      the bite. MRI of brain revealed massive left middle cerebral artery (MCA)
      territory infarct. The magnetic resonance angiography showed non-visualisation of
      left internal carotid artery (ICA) and MCA. Coagulation parameters were normal.
      Sudden complete occlusion of left ICA was probably secondary to cardioembolic
      phenomenon leading to massive infarct. Despite aggressive medical and supportive
      measures, she clinically worsened rapidly to Glasgow Coma Scale of 3/15 over next
      6 hours and succumbed to her illness the next day.

PMID- 29025780
TI  - Cryptococcus neoformans osteomyelitis and intramuscular abscess in a liver
      transplant patient.
AB  - Cryptococcus neoformans is an important pathogen that can cause severe illness
      and mortality in immunocompromised patients. We highlight here the case of a 53
      year-old man presenting to hospital 4 years postliver transplant with fever,
      acute renal failure and a medial thigh lesion. Initially treated as bacterial
      sepsis, the patient failed to improve on broad-spectrum antibiotics. Further
      investigations revealed disseminated cryptococcemia complicated by patellar
      osteomyelitis and an intramuscular abscess. Unfortunately, although the patient
      initially showed signs of clinical improvement after starting standard antifungal
      agents, he deteriorated and died secondary to acute renal failure. Osteomyelitis
      is a rare manifestation of cryptococcal infection for which there is often a
      significant delay to diagnosis and treatment. This is the fourth reported case of
      cryptococcal osteomyelitis in a liver transplant patient and underlines the
      importance of considering fungal infections in the differential diagnosis of
      osseous lesions in solid organ transplant and other immunocompromised patients.

PMID- 29025781
TI  - Subclinical meningoventriculitis as a cause of obstructive hydrocephalus.
AB  - Communicating hydrocephalus may complicate infantile bacterial meningitis,
      typically presenting with systemic features of infection. We report a rare case
      of 'subclinical meningoventriculitis' causing obstructive hydrocephalus and its
      challenging management. A healthy 10-week-old immunocompetent male patient
      presented with failure to thrive and vomiting, secondary to presumed gastro
      oesophageal reflux. The child was neurologically alert, afebrile with normal
      inflammatory markers. Progressive macrocephaly prompted an MRI confirming
      triventricular hydrocephalus secondary to aqueductal stenosis. An endoscopic
      third ventriculostomy was performed however abandoned intraoperatively due to the
      unexpected finding of intraventricular purulent cerebrospinal fluid. A 6-week
      course of intravenous ceftriaxone was commenced for Escherichia coli
      meningoventriculitis. However, the child was readmitted 18 days postoperatively
      with acute hydrocephalus requiring a ventricular washout and staged
      ventriculoperitoneal shunt insertion at 4 weeks. Serial head circumference
      measurements are paramount in the assessment of a paediatric patient. In an
      immunocompetent child, a subclinical fibropurulent meningoventriculitis can
      result in several management challenges.

PMID- 29025782
TI  - Olfactory bulb agenesis with normal sexual hormones.
AB  - An 18-year-old Caucasian man presented with a lack of sense of surrounding smell.
      The problem was first noticed when a family member discussed the smell of the
      food, which he had no idea what it was. The patient had normal development and
      sexual function, no history of trauma, surgery, chemical exposure or infection.
      Physical examination revealed no significant abnormalities. Smell threshold test
      using phenyl-ethyl-alcohol revealed bilateral anosmia. MRI showed bilateral
      aplastic olfactory bulbs and tracts associated with absent cortical growth of the
      olfactory sulci and asymmetrical gyrus rectus. Circulating hormones including
      cortisol, growth hormone, insulin-like growth factor 1, adrenocorticotropic
      hormone, thyroid hormones, follicle-stimulating hormone, luteinizing hormone,
      prolactin and testosterone were within normal ranges. Doppler ultrasound showed
      normal testis with bilateral supratesticular varicoceles. Given the loss of
      warning smell sensation, counselling for daily living precautions especially
      those related to gas, fire and rotten food was given.

PMID- 29025783
TI  - Syncope from radiation-induced baroreceptor failure.
AB  - Orthostatic hypotension has a vast differential that has been previously
      described throughout the literature. However, baroreceptor failure as a sequela
      of head and neck radiation is not often recognised as an important cause of
      dramatic haemodynamic variability. As a result, individuals suffering from
      baroreceptor failure likely have been undertreated. Herein, we report a case of a
      patient with a history of radiation to the neck for squamous cell carcinoma of
      the tongue and resultant baroreceptor failure resulting in syncope.

PMID- 29025784
TI  - Hydatid cyst of the thigh: a challenging diagnosis.

PMID- 29025785
TI  - Live 'Baby dance' among the red blood cells.

PMID- 29025786
TI  - Disparity between Nephrologists' Opinions and Contemporary Practices for
      Community Follow-Up after AKI Hospitalization.
AB  - BACKGROUND AND OBJECTIVES: Recent guidelines suggest that patients should be
      evaluated after AKI for resolution versus progression of CKD. There is
      uncertainty as to the role of nephrologists in this process. The objective of
      this study was to compare the follow-up recommendations from nephrologists with
      contemporary processes of care for varying scenarios of patients hospitalized
      with AKI. DESIGN, SETTING PARTICIPANTS, & MEASUREMENTS: We surveyed Canadian
      nephrologists using a series of clinical vignettes of patients hospitalized with
      severe AKI and asked them to rank their likelihood of recommending follow-up for
      each patient after hospital discharge. We compared these responses with
      administrative health data on rates of community follow-up with nephrologists for
      patients hospitalized with AKI in Alberta, Canada between 2005 and 2014. RESULTS:
      One hundred forty-five nephrologists participated in the survey (46% of the
      physician membership of the Canadian Society of Nephrology). Nephrologists
      surveyed indicated that they would definitely or probably re-evaluate patients in
      87% of the scenarios provided, with a higher likelihood of follow-up for patients
      with a history of preexisting CKD (89%), heart failure (92%), receipt of acute
      dialysis (91%), and less complete recovery of kidney function (98%). In contrast,
      only 24% of patients with similar characteristics were seen by a nephrologist in
      Alberta within 1 year after a hospitalization with AKI, with a trend toward lower
      rates of follow-up over more recent years of the study. Follow-up with a
      nephrologist was significantly less common among patients over the age of 80
      years old (20%) and more common among patients with preexisting CKD (43%) or a
      nephrology consultation before or during AKI hospitalization (78% and 41%,
      respectively). CONCLUSIONS: There is a substantial disparity between the opinions
      of nephrologists and actual processes of care for nephrology evaluation of
      patients after hospitalization with severe AKI.

PMID- 29025787
TI  - A Markov Analysis of Screening for Late-Onset Cytomegalovirus Disease in
      Cytomegalovirus High-Risk Kidney Transplant Recipients.
AB  - BACKGROUND AND OBJECTIVES: Management strategies are unclear for late-onset
      cytomegalovirus infection occurring beyond 6 months of antiviral prophylaxis in
      cytomegalovirus high-risk (cytomegalovirus IgG positive to cytomegalovirus IgG
      negative) kidney transplant recipients. Hybrid strategies (prophylaxis followed
      by screening) have been investigated but with inconclusive results. There are
      clinical and potential cost benefits of preventing cytomegalovirus-related
      hospitalizations and associated increased risks of patient and graft failure. We
      used decision analysis to evaluate the utility of postprophylaxis screening for
      late-onset cytomegalovirus infection. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: We used the Markov decision analysis model incorporating costs and
      utilities for various cytomegalovirus clinical states (asymptomatic
      cytomegalovirus, mild cytomegalovirus infection, and cytomegalovirus infection
      necessitating hospitalization) to estimate cost-effectiveness of postprophylaxis
      cytomegalovirus screening strategies. Five strategies were compared: no screening
      and screening at 1-, 2-, 3-, or 4-week intervals. Progression to severe
      cytomegalovirus infection was modeled on cytomegalovirus replication kinetics.
      Incremental cost-effectiveness ratios were calculated as a ratio of cost
      difference between two strategies to difference in quality-adjusted life-years
      starting with the low-cost strategy. One-way and probabilistic sensitivity
      analyses were performed to test model's robustness. RESULTS: There was an
      incremental gain in quality-adjusted life-years with increasing screening
      frequency. Incremental cost-effectiveness ratios were $783 per quality-adjusted
      life-year (every 4 weeks over no screening), $1861 per quality-adjusted life-year
      (every 3 weeks over every 4 weeks), $10,947 per quality-adjusted life-year (every
      2 weeks over every 3 weeks), and $197,086 per quality-adjusted life-year (weekly
      over every 2 weeks). Findings were sensitive to screening cost, cost of
      hospitalization, postprophylaxis cytomegalovirus incidence, and graft loss after
      cytomegalovirus infection. No screening was favored when willingness to pay
      threshold was <$14,000 per quality-adjusted life-year, whereas screening weekly
      was favored when willingness to pay threshold was >$185,000 per quality-adjusted
      life-year. Screening every 2 weeks was the dominant strategy between willingness
      to pay range of $14,000-$185,000 per quality-adjusted life-year. CONCLUSIONS: In
      cytomegalovirus high-risk kidney transplant recipients, compared with no
      screening, screening for postprophylactic cytomegalovirus viremia is associated
      with gains in quality-adjusted life-years and seems to be cost effective. A
      strategy of screening every 2 weeks was the most cost-effective strategy across a
      wide range of willingness to pay thresholds.

PMID- 29025791
TI  - What if alcohol were harmful, even in moderation?

PMID- 29025788
TI  - Brief Mindfulness Meditation for Depression and Anxiety Symptoms in Patients
      Undergoing Hemodialysis: A Pilot Feasibility Study.
AB  - BACKGROUND AND OBJECTIVES: Up to 50% of patients undergoing hemodialysis suffer
      from symptoms of depression and/or anxiety. Access to traditional
      pharmacotherapies and psychotherapies for depression or anxiety in this patient
      population has been inadequate. The objective of this study was to investigate
      the feasibility and effectiveness of brief mindfulness meditation intervention
      for patients on hemodialysis with depression and anxiety symptoms. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: This study was a randomized, controlled,
      assessor-blinded trial conducted in an urban hemodialysis unit. Forty-one
      patients were randomly assigned to intervention (n=21) and treatment-as-usual
      (n=20) groups. The intervention group received an 8-week individual chairside
      meditation intervention lasting 10-15 minutes, three times a week during
      hemodialysis. Feasibility outcomes were primarily assessed: enrollment rates,
      intervention completion rates, and intervention tolerability. Symptoms of
      depression and anxiety were measured using the Patient Health Questionnaire (PHQ
      9) and the General Anxiety Disorder-7 (GAD-7). RESULTS: Of those deemed eligible
      for the study, 67% enrolled (41 of 61). Of the participants randomized to the
      intervention group, 71% completed the study, with meditation being well tolerated
      (median rating of 8 of 10 in a Likert scale; interquartile range=10-5 of 10).
      Barriers to intervention delivery included frequent hemodialysis shift changes,
      interruptions by staff or alarms, space constraints, fluctuating participant
      medical status, and participant fatigue. Meditation was associated with
      subjective benefits but no statistically significant effect on depression scores
      (change in PHQ-9, -3.0+/-3.9 in the intervention group versus -2.0+/-4.7 in
      controls; P=0.45) or anxiety scores (change in GAD-7, -0.9+/-4.6 versus -0.8+/
      4.8; P=0.91). CONCLUSIONS: On the basis of the results of this study, mindfulness
      meditation appears to be feasible and well tolerated in patients on hemodialysis
      with anxiety and depression symptoms. The study did not reveal significant
      effects of the interventions on depression and anxiety scores. PODCAST: This
      article contains a podcast at https://www.asn
      online.org/media/podcast/CJASN/2017_10_12_CJASNPodcast_17_12_.mp3.

PMID- 29025792
TI  - ?

PMID- 29025789
TI  - FGF23 and Left Ventricular Hypertrophy in Children with CKD.
AB  - BACKGROUND AND OBJECTIVES: High plasma concentration of fibroblast growth factor
      23 (FGF23) is a risk factor for left ventricular hypertrophy (LVH) in adults with
      CKD, and induces myocardial hypertrophy in experimental CKD. We hypothesized that
      high FGF23 levels associate with a higher prevalence of LVH in children with CKD.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed echocardiograms and
      measured plasma C-terminal FGF23 concentrations in 587 children with mild-to
      moderate CKD enrolled in the Chronic Kidney Disease in Children (CKiD) study. We
      used linear and logistic regression to analyze the association of plasma FGF23
      with left ventricular mass index (LVMI) and LVH (LVMI >=95th percentile),
      adjusted for demographics, body mass index, eGFR, and CKD-specific factors. We
      also examined the relationship between FGF23 and LVH by eGFR level. RESULTS:
      Median age was 12 years (interquartile range, 8-15) and eGFR was 50 ml/min per
      1.73 m2 (interquartile range, 38-64). Overall prevalence of LVH was 11%. After
      adjustment for demographics and body mass index, the odds of having LVH was
      higher by 2.53 (95% confidence interval, 1.28 to 4.97; P<0.01) in participants
      with FGF23 concentrations >=170 RU/ml compared with those with FGF23<100 RU/ml,
      but this association was attenuated after full adjustment. Among participants
      with eGFR>=45 ml/min per 1.73 m2, the prevalence of LVH was 5.4%, 11.2%, and
      15.3% for those with FGF23 <100 RU/ml, 100-169 RU/ml, and >=170 RU/ml,
      respectively (Ptrend=0.01). When eGFR was >=45 ml/min per 1.73 m2, higher FGF23
      concentrations were independently associated with LVH (fully adjusted odds ratio,
      3.08 in the highest versus lowest FGF23 category; 95% confidence interval, 1.02
      to 9.24; P<0.05; fully adjusted odds ratio, 2.02 per doubling of FGF23; 95%
      confidence interval, 1.29 to 3.17; P<0.01). By contrast, in participants with
      eGFR<45 ml/min per 1.73 m2, FGF23 did not associate with LVH. CONCLUSIONS: Plasma
      FGF23 concentration >=170 RU/ml is an independent predictor of LVH in children
      with eGFR>=45 ml/min per 1.73 m2.

PMID- 29025793
TI  - Time for change: Benefits of a plant-based diet.

PMID- 29025794
TI  - ?

PMID- 29025795
TI  - Should peanut be allowed in schools? Yes.

PMID- 29025796
TI  - Should peanut be allowed in schools? No.

PMID- 29025797
TI  - Estimating prognosis is a poor use of physicians' time.

PMID- 29025798
TI  - Strategy to diminish nonresponse.

PMID- 29025799
TI  - Correction.

PMID- 29025801
TI  - Zinc supplementation for pediatric pneumonia.
AB  - Question Among young children suffering from pneumonia, zinc deficiency has been
      documented in many countries. Is supplementation with zinc effective in the
      treatment and prevention of childhood pneumonia? Answer Several studies reported
      that zinc supplementation for more than 3 months was effective for preventing
      pneumonia in children younger than 5 years of age; however, the evidence is not
      sufficient to confirm its prophylactic properties if it is given for shorter
      periods of time. Adjunctive zinc supplementation for treatment of pneumonia has
      failed to show a benefit.

PMID- 29025802
TI  - Benign pneumatosis intestinalis: Dilemma for primary care clinicians.

PMID- 29025800
TI  - Approach to recurrent fever in childhood.
AB  - OBJECTIVE: To provide an approach to recurrent fever in childhood, explain when
      infections, malignancies, and immunodeficiencies can be excluded, and describe
      the features of periodic fever and other autoinflammatory syndromes. SOURCES OF
      INFORMATION: PubMed was searched for relevant articles regarding the
      pathogenesis, clinical findings, diagnosis, prognosis, and treatment of periodic
      fever and autoinflammatory syndromes. MAIN MESSAGE: Fever is a common sign of
      illness in children and is most frequently due to infection. However, when acute
      and chronic infections have been excluded and when the fever pattern becomes
      recurrent or periodic, the expanding spectrum of autoinflammatory diseases,
      including periodic fever syndromes, should be considered. Familial Mediterranean
      fever is the most common inherited monogenic autoinflammatory syndrome, and early
      recognition and treatment can prevent its life-threatening complication, systemic
      amyloidosis. Periodic fever, aphthous stomatitis, pharyngitis, and adenitis
      syndrome is the most common periodic fever syndrome in childhood; however, its
      underlying genetic basis remains unknown. CONCLUSION: Periodic fever syndromes
      and other autoinflammatory diseases are increasingly recognized in children and
      adults, especially as causes of recurrent fevers. Individually they are rare, but
      a thorough history and physical examination can lead to their early recognition,
      diagnosis, and appropriate treatment.

PMID- 29025803
TI  - Human orf: Atypical rash in an urban medical practice.

PMID- 29025804
TI  - Complete blood count for screening?

PMID- 29025805
TI  - ?

PMID- 29025806
TI  - Radiation and medical procedures: How do we do no harm?

PMID- 29025807
TI  - Examination outcomes and work locations of international medical graduate family
      medicine residents in Canada.
AB  - OBJECTIVE: To describe the postgraduate medical education (PGME) examination
      outcomes and work locations of international medical graduates (IMGs); and to
      identify differences between Canadians studying abroad (CSAs) and non-CSAs.
      DESIGN: Cohort study using data from the National IMG Database and Scott's
      Medical Database. SETTING: Canada. PARTICIPANTS: All IMGs who had first entered a
      family medicine residency program between 2005 and 2009, with the exclusion of US
      graduates, visa trainees, and fellowship trainees. MAIN OUTCOME MEASURES: We
      examined 4 outcomes: passing the Medical Council of Canada Qualifying Examination
      Part 2 (MCCQE2), obtaining Certification in Family Medicine (CCFP), working in
      Canada within 2 years of completing PGME training, and working in Canada in 2015.
      RESULTS: Of the 876 residents in the study, 96.1% passed the MCCQE2, 78.1%
      obtained a specialty designation, 37.7% worked in Canada within 2 years after
      their PGME, and 91.2% worked in Canada in 2015. Older graduates were more likely
      (odds ratio [OR] = 3.45; 95% CI 1.52 to 7.69) than recent graduates were to pass
      the MCCQE2, and residents who participated in a skills assessment program before
      their PGME training were more likely (OR = 9.60; 95% CI 1.29 to 71.63) than those
      who had not were to pass the MCCQE2. Women were more likely (OR = 1.67; 95% CI
      1.20 to 2.33) to obtain a specialty designation than men were. Recent graduates
      were more likely (OR = 1.36; 95% CI 1.03 to 1.79) than older graduates were to
      work in Canada following training. Residents who were eligible for a full licence
      were more likely (OR = 3.72; 95% CI 2.30 to 5.99) to work in Canada in 2015 than
      those who were not eligible for a full licence were. CONCLUSION: While most IMGs
      who entered the family medicine PGME program passed the MCCQE2, 1 in 5 did not
      obtain Certification. Most IMG residents remain in Canada. Canadians studying
      abroad and non-CSA IMGs share similar examination success rates and retention
      rates.

PMID- 29025808
TI  - Learning the truth first-hand about reconciliation: Community-based research and
      First Nations health in rural Manitoba.

PMID- 29025810
TI  - Leading from where you teach: Educational leader role within the Fundamental
      Teaching Activities Framework.

PMID- 29025812
TI  - ?

PMID- 29025811
TI  - Lifeblood of a discipline.

PMID- 29025813
TI  - ?

PMID- 29025814
TI  - Value and limits of experience.

PMID- 29025815
TI  - ?

PMID- 29025816
TI  - ?

PMID- 29025817
TI  - ?

PMID- 29025818
TI  - Mental health and addictions capacity building for community health centres in
      Ontario.
AB  - PROBLEM ADDRESSED: In recent years, there has been increased recognition in
      Canada of the need to strengthen mental health services in primary health care
      (PHC). Collaborative models, including partnerships between PHC and specialized
      mental health care providers, have emerged as effective ways for improving access
      to mental health care and strengthening clinical capacity. Primary health care
      physicians and other health professionals are well positioned to facilitate the
      early detection of mental disorders and provide appropriate treatment and follow
      up care, helping to tackle stigma toward mental health problems in the process.
      OBJECTIVE OF PROGRAM: This 4-year mental health and addiction capacity-building
      initiative for PHC addressed competency needs at the individual,
      interprofessional, and organizational levels. PROGRAM DESCRIPTION: The program
      included 5 key components: a needs assessment; interprofessional education;
      mentoring; development of organizational mental health and addiction action plans
      for each participating community health centre; and creation of an advanced
      resource manual to support holistic and culturally competent collaborative mental
      health care. A comprehensive evaluation framework using a mixed-methods approach
      was applied from the initiation of the program. A total of 184 health workers in
      10 community health centres in Ontario participated in the program, including
      physicians, nurses, social workers, and administrative staff. CONCLUSION:
      Evaluation findings demonstrated high satisfaction with the training, improved
      competencies, and individual behavioural and organizational changes. By building
      capacity to integrate holistic and culturally appropriate care, this competency
      based program is a promising model with strong potential to be adapted and scaled
      up for PHC organizations nationally and internationally.

PMID- 29025819
TI  - Time in therapeutic range: Warfarin anticoagulation for atrial fibrillation in a
      community-based practice.
AB  - OBJECTIVE: To evaluate the effectiveness of an outpatient, nurse-administered
      warfarin anticoagulation protocol for the treatment of atrial fibrillation, and
      to identify clinical or biographical data that predict poor international
      normalized ratio control. DESIGN: Retrospective cohort study. SETTING: St Paul
      Family Health Network in Brantford, Ont. PARTICIPANTS: A total of 150 patients
      with nonvalvular atrial fibrillation. MAIN OUTCOME MEASURES: Time in therapeutic
      range (TTR) for each patient and for the clinic overall. The groups of patients
      above and below a target TTR of 60% were compared by stepwise binomial logistic
      regression. RESULTS: A time-weighted average TTR for the clinic was determined to
      be 58.76%, based on 183 452 patient-days taking warfarin. The regression analysis
      did not find a statistically significant association between TTR and any
      predictors. A trend indicating a 5-fold increase in the odds of inadequate
      anticoagulation was observed in current smokers (odds ratio of 4.71; 95% CI 0.97
      to 22.93). CONCLUSION: Compared with data from prospective randomized trials and
      meta-analysis, the anticoagulation protocol employed at the St Paul Family Health
      Network produced an average TTR near the lower end of the target threshold.
      Current smokers might be at greater risk of being below this target.

PMID- 29025821
TI  - ?

PMID- 29025822
TI  - ?

PMID- 29025820
TI  - Well-being of family medicine graduates.
AB  - OBJECTIVE: To determine family medicine graduates' professional and personal well
      being, general health status, stress levels, coping strategies, and the degree to
      which they felt supported or isolated in professional life; and to compare
      findings by sex, practice location, and location of medical school (Canadian
      medical graduates [CMGs] vs international medical graduates [IMGs]). DESIGN:
      Retrospective, cross-sectional survey. SETTING: University of Alberta in Edmonton
      and the University of Calgary in Alberta. PARTICIPANTS: A total of 651 graduates
      who completed one of the family medicine residency programs during 2006 to 2011.
      MAIN OUTCOME MEASURES: Using a 5-point Likert scale, graduates rated their
      general health status, their personal and professional well-being, their level of
      stress, and the degree to which they felt supported or isolated in professional
      life. Respondents also identified important life events, their caregiving roles,
      and stress-coping strategies. RESULTS: Of 651 graduates, 307 (47.2%) responded to
      the survey. Personal and professional well-being and general health status were
      rated as very good or excellent by 72.0%, 76.6%, and 74.7% of graduates,
      respectively. Overall, 39.3% reported high or extremely high levels of stress,
      with CMGs exhibiting significantly higher stress levels than IMGs (P = .02).
      Stress scores were inversely related to personal and professional well-being and
      health status. In terms of coping strategies, a significantly greater proportion
      of female than male graduates reported talking to colleagues (76.5% vs 64.3%; P =
      .026) and seeking professional counseling (18.7% vs 6.1%; P = .002). Also, a
      significantly greater proportion of IMGs than CMGs (52.9% vs 32.5%; P = .003), as
      well as those in rural (35.8%) or urban (49.3%) practices than those in
      metropolitan locations (30.1%) (P = .03), turned to spiritual or religious
      practices for stress management. Of all respondents, 54.8% felt highly or
      extremely supported and 18.4% felt isolated in their professional lives.
      CONCLUSION: While family medicine graduates are primarily healthy and have a
      strong sense of personal and professional well-being, many experience high levels
      of stress. Coping strategies generally include social contact with family,
      friends, or colleagues and differ by sex, whether respondents are CMGs or IMGs,
      and practice location. Professional isolation appears to be prevalent in both
      rural and urban practice locations. Physician well-being programs should include
      a multifaceted approach to accommodate a range of physician preferences.

PMID- 29025823
TI  - STANDING Collaboration: a study protocol for developing clinical standards.
AB  - INTRODUCTION: Despite widespread availability of clinical practice guidelines
      (CPGs), considerable gaps continue between the care that is recommended
      ('appropriate care') and the care provided. Problems with current CPGs are
      commonly cited as barriers to providing 'appropriate care'.Our study aims to
      develop and test an alternative method to keep CPGs accessible and up to date.
      This method aims to mitigate existing problems by using a single process to
      develop clinical standards (embodied in clinical indicators) collaboratively with
      researchers, healthcare professionals, patients and consumers. A transparent and
      inclusive online curated (purpose-designed, custom-built, wiki-type) system will
      use an ongoing and iterative documentation process to facilitate synthesis of up
      to-date information and make available its provenance. All participants are
      required to declare conflicts of interest. This protocol describes three phases:
      engagement of relevant stakeholders; design of a process to develop clinical
      standards (embodied in indicators) for 'appropriate care' for common medical
      conditions; and evaluation of our processes, products and feasibility. METHODS
      AND ANALYSIS: A modified e-Delphi process will be used to gain consensus on
      'appropriate care' for a range of common medical conditions. Clinical standards
      and indicators will be developed through searches of national and international
      guidelines, and formulated with explicit criteria for inclusion, exclusion, time
      frame and setting. Healthcare professionals and consumers will review the
      indicators via the wiki-based modified e-Delphi process. Reviewers will declare
      conflicts of interest which will be recorded and managed according to an
      established protocol. The provenance of all indicators and suggestions included
      or excluded will be logged from indicator inception to finalisation. A mixed
      methods formative evaluation of our research methodology will be undertaken.
      ETHICS AND DISSEMINATION: Human Research Ethics Committee approval has been
      received from the University of South Australia. We will submit the results of
      the study to relevant journals and offer national and international
      presentations.

PMID- 29025826
TI  - Patient characteristics of the Accident and Emergency Department of Kenyatta
      National Hospital, Nairobi, Kenya: a cross-sectional, prospective analysis.
AB  - BACKGROUND: Resource-limited settings are increasingly experiencing a 'triple
      burden' of disease, composed of trauma, non-communicable diseases (NCDs) and
      known communicable disease patterns. However, the epidemiology of acute and
      emergency care is not well characterised and this limits efforts to further
      develop emergency care capacity. OBJECTIVE: To define the burden of disease by
      describing the patient population presenting to the Accident and Emergency
      Department (A&E) at Kenyatta National Hospital (KNH) in Kenya. METHODS: We
      completed a prospective descriptive assessment of patients in KNH's A&E obtained
      via systematic sampling over 3 months. Research assistants collected data
      directly from patients and their charts. Chief complaint and diagnosis codes were
      grouped for analysis. Patient demographic characteristics were described using
      the mean and SD for age and n and percentages for categorical variables.
      International Classification of Disease 10 codes were categorised by 2013 Global
      Burden of Disease Study methods. RESULTS: Data were collected prospectively on
      402 patients with an average age of 36 years (SD 19), and of whom, 50% were
      female. Patients were most likely to arrive by taxi or bus (39%), walking (28%)
      or ambulance (17%). Thirty-five per cent of patients were diagnosed with NCDs,
      24% with injuries and 16% with communicable diseases, maternal and neonatal
      conditions. Overall, head injury was the single most common final diagnosis and
      occurred in 32 (8%) patients. The most common patient-reported mechanism for head
      injury was road traffic accident (39%). CONCLUSION: This study estimates the
      characteristics of the A&E population at a tertiary centre in Kenya and
      highlights the triple burden of disease. Our findings emphasise the need for
      further development of emergency care resources and training to better address
      patient needs in resource-limited settings, such as KNH.

PMID- 29025827
TI  - Influence of social deprivation on provision of bariatric surgery: 10-year
      comparative ecological study between two UK specialist centres.
AB  - OBJECTIVE: To investigate the effect of residential location and socioeconomic
      deprivation on the provision of bariatric surgery. DESIGN: Retrospective cross
      sectional ecological study. SETTING: Patients resident local to one of two
      specialist bariatric units, in different regions of the UK, who received obesity
      surgery between 2003 and 2013. METHODS: Demographic data were collected from
      prospectively collected databases. Index of Multiple Deprivation (IMD 2010) was
      used as a measure of socioeconomic status. Obesity prevalences were obtained from
      Public Health England (2006). Patients were split into three IMD tertiles (high,
      median, low) and also tertiles of time. A generalised linear model was generated
      for each time period to investigate the effect of socioeconomic deprivation on
      the relationship between bariatric case count and prevalence of obesity. We used
      these to estimate surgical intervention provided in each population in each
      period at differing levels of deprivation. RESULTS: Data were included from 1163
      bariatric cases (centre 1-414, centre 2-749). Incidence rate ratios (IRRs) were
      calculated to measure the associations between predictor and response variables.
      Associations were highly non-linear and changed over the 10-year study period. In
      general, the relationship between surgical case volume and obesity prevalence has
      weakened over time, with high volumes becoming less associated with prevalence of
      obesity. DISCUSSION: As bariatric services have matured, the associations between
      demand and supply factors have changed. Socioeconomic deprivation is not
      apparently a barrier to service provision more recently, but the positive
      relationships between obesity and surgical volume we would expect to find are
      absent. This suggests that interventions are not being taken up in the areas of
      need. We recommend a more detailed national analysis of the relationship between
      supply side and demand side factors in the provision of bariatric surgery.

PMID- 29025825
TI  - Comparison of the cerebroprotective effect of inhalation anaesthesia and total
      intravenous anaesthesia in patients undergoing cardiac surgery with
      cardiopulmonary bypass: a systematic review and meta-analysis.
AB  - OBJECTIVE: Neurological dysfunction remains a devastating postoperative
      complication in patients undergoing cardiac surgery with cardiopulmonary bypass
      (CPB), and previous studies have shown that inhalation anaesthesia and total
      intravenous anaesthesia (TIVA) may produce different degrees of cerebral
      protection in these patients. Therefore, we conducted a systematic literature
      review and meta-analysis to compare the neuroprotective effects of inhalation
      anaesthesia and TIVA. DESIGN: Searching in PubMed, EMBASE, Science
      Direct/Elsevier, China National Knowledge Infrastructure and Cochrane Library up
      to August 2016, we selected related randomised controlled trials for this meta
      analysis. RESULTS: A total of 1485 studies were identified. After eliminating
      duplicate articles and screening titles and abstracts, 445 studies were
      potentially eligible. After applying exclusion criteria (full texts reported as
      abstracts, review article, no control case, lack of outcome data and so on), 13
      studies were selected for review. Our results demonstrated that the primary
      outcome related to S100B level in the inhalation anaesthesia group was
      significantly lower than in the TIVA group after CPB and 24 hours postoperatively
      (weighted mean difference (WMD); 95% CI (CI): -0.41(-0.81 to -0.01), -0.32 (-0.59
      to -0.05), respectively). Among secondary outcome variables, mini-mental state
      examination scores of the inhalation anaesthesia group were significantly higher
      than those of the TIVA group 24 hours after operation (WMD (95% CI): 1.87 (0.82
      to 2.92)), but no significant difference was found in arteriovenous oxygen
      content difference, cerebral oxygen extraction ratio and jugular bulb venous
      oxygen saturation, which were assessed at cooling and rewarming during CPB.
      CONCLUSION: This study demonstrates that anaesthesia with volatile agents appears
      to provide better cerebral protection than TIVA for patients undergoing cardiac
      surgery with CPB, suggesting that inhalation anaesthesia may be more suitable for
      patients undergoing cardiac surgery.

PMID- 29025824
TI  - Development of an evidence-based complex intervention for community
      rehabilitation of patients with hip fracture using realist review, survey and
      focus groups.
AB  - OBJECTIVES: To develop an evidence and theory-based complex intervention for
      improving outcomes in elderly patients following hip fracture. DESIGN: Complex
      intervention development (Medical Research Council (MRC) framework phase I) using
      realist literature review, surveys and focus groups of patients and
      rehabilitation teams. SETTING: North Wales. PARTICIPANTS: Surveys of therapy
      managers (n=13), community and hospital-based physiotherapists (n=129) and
      occupational therapists (n=68) throughout the UK. Focus groups with patients
      (n=13), their carers (n=4) and members of the multidisciplinary rehabilitation
      teams in North Wales (n=13). RESULTS: The realist review provided understanding
      of how rehabilitation interventions work in the real-world context and three
      programme theories were developed: improving patient engagement by tailoring the
      intervention to individual needs; reducing fear of falling and improving self
      efficacy to exercise and perform activities of daily living; and coordination of
      rehabilitation delivery. The survey provided context about usual rehabilitation
      practice; focus groups provided data on the experience, acceptability and
      feasibility of rehabilitation interventions. An intervention to enhance usual
      rehabilitation was developed to target these theory areas comprising: a physical
      component consisting of six additional therapy sessions; and a psychological
      component consisting of a workbook to enhance self-efficacy and a patient-held
      goal-setting diary for self-monitoring. CONCLUSIONS: A realist approach may have
      advantages in the development of evidence-based interventions and can be used in
      conjunction with other established methods to contribute to the development of
      potentially more effective interventions. A rehabilitation intervention was
      developed which can be tested in a future randomised controlled trial (MRC
      framework phases II and III). TRIAL REGISTRATION NUMBER: ISRCTN22464643, Pre
      results.

PMID- 29025828
TI  - Diurnal cortisol and mental well-being in middle and older age: evidence from
      four cohort studies.
AB  - OBJECTIVES: We conducted an individual participant meta-analysis to test the
      hypothesis that cortisol patterns indicative of dysregulated hypothalamic
      pituitary-adrenal axis functioning would be prospectively associated with poorer
      well-being at follow-up. SETTING: Four large UK-based cohort studies.
      PARTICIPANTS: Those providing valid salivary or serum cortisol samples (n=7515
      for morning cortisol; n=1612 for cortisol awakening response) at baseline (age 44
      82) and well-being data on the Warwick Edinburgh Mental Wellbeing Scale at follow
      up (0-8 years) were included. RESULTS: Well-being was not associated with morning
      cortisol, diurnal slope or awakening response though a borderline association
      with evening cortisol was found. Adjusting for sex and follow-up time, each 1 SD
      increase in evening cortisol was associated with a -0.47 (95% CI -1.00 to 0.05)
      point lower well-being. This was attenuated by adjustment for body mass index,
      smoking and socioeconomic position. Between-study heterogeneity was low.
      CONCLUSIONS: This study does not support the hypothesis that diurnal cortisol is
      prospectively associated with well-being up to 8 years later. However,
      replication in prospective studies with cortisol samples over multiple days is
      required.

PMID- 29025829
TI  - Is an opportunistic primary care-based intervention for non-responders to bowel
      screening feasible and acceptable? A mixed-methods feasibility study in Scotland.
AB  - OBJECTIVES: We aimed to test whether a brief, opportunistic intervention in
      general practice was a feasible and acceptable way to engage with bowel screening
      non-responders. DESIGN: This was a feasibility study testing an intervention
      which comprised a brief conversation during routine consultation, provision of a
      patient leaflet and instructions to request a replacement faecal occult blood
      test kit. A mixed-methods approach to evaluation was adopted. Data were collected
      from proformas completed after each intervention, from the Bowel Screening Centre
      database and from questionnaires. Semi-structured interviews were carried out. We
      used descriptive statistics, content and framework analysis to determine
      intervention feasibility and acceptability. PARTICIPANTS: Bowel screening non
      responders (as defined by the Scottish Bowel Screening Centre) and primary care
      professionals working in five general practices in Lothian, Scotland. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Several predefined feasibility parameters were
      assessed, including numbers of patients engaging in conversation, requesting a
      replacement kit and returning it, and willingness of primary care professionals
      to deliver the intervention. RESULTS: The intervention was offered to 258
      patients in five general practices: 220 (87.0%) engaged with the intervention, 60
      (23.3%) requested a new kit, 22 (8.5%) kits were completed and returned.
      Interviews and questionnaires suggest that the intervention was feasible,
      acceptable and consistent with an existing health prevention agenda. Reported
      challenges referred to work-related pressures, time constraints and practice
      priorities. CONCLUSIONS: This intervention was acceptable and resulted in a
      modest increase in non-responders participating in bowel screening, although
      outlined challenges may affect sustained implementation. The strategy is also
      aligned with the increasing role of primary care in promoting bowel screening.

PMID- 29025830
TI  - Randomised controlled pilot trial of an exercise plus behaviour change
      intervention in people with multiple sclerosis: the Step it Up study.
AB  - OBJECTIVE: To investigate feasibility of multiple sclerosis (MS) exercise
      guidelines for inactive people with MS (PwMS) and to examine preliminary efficacy
      for walking. To investigate effect of augmenting that intervention with education
      based on social cognitive theory (SCT). DESIGN: Pilot multicentre, double-blind,
      randomised, parallel, controlled trial. SETTING: Community-delivered programme.
      PARTICIPANTS: Sixty-five physically inactive PwMS walked independently, scored 0
      3 on the Patient Determined Disease Steps Scale, had no MS relapse or change in
      MS medication in 12 weeks. INTERVENTIONS: 10-week exercise plus SCT education
      (SCT) compared with exercise plus attention control education (CON). OUTCOME
      MEASURES: Six-Minute Walk Test (6MWT), Timed Up and Go (TUG) test and Multiple
      Sclerosis Walking Scale-12 (MSWS-12). RESULTS: 174 expressed interest, 92 were
      eligible and 65 enrolled (SCT, n=32; CON, n=33). The intervention was feasible
      and delivered as intended. 68% of SCT group and 50% of control group met the
      exercise guidelines after intervention. Using linear mixed effects models,
      intention-to-treat basis, there was insufficient evidence for difference between
      the groups over the trial (6MWT, p=0.30; TUG, p=0.4; MSWS-12, p=0.8). Using
      secondary analysis of a cohort with data for>=3 assessments (SCT, n=21; CON,
      n=20), there was significant treatment effect favouring the intervention group
      (p=0.04) with mean effect for 6MWT 39.0 m (95% CI 2.26 to 75.73) at 12 weeks and
      40.0 m (95% CI 2.3 to 77.8) at 36 weeks. Both groups improved significantly in
      6MWT following 10-week intervention (SCT, mean ?=83.02, SD=60.1, p<=0.01; CON,
      mean ?=56.92, SD=73.5, p<=0.01), TUG (SCT, ?=-0.70, SD=1.25, p<=0.01; CON, ?=
      0.54, SD=0.95, p<=0.01) and MSWS-12 (SCT, ?=-8.03, SD=16.18, p=0.02; CON, ?=
      0.86, SD=18.74, p=0.81). CONCLUSIONS: A 10-week exercise programme based on the
      MS exercise guidelines for improving walking in previously inactive PwMS was
      feasible. There is marginal evidence of a treatment effect in favour of the
      exercise plus SCT intervention at 12 and 36 weeks. TRIAL REGISTRATION NUMBER:
      NCT02301442; Results.

PMID- 29025831
TI  - Spending on social and public health services and its association with homicide
      in the USA: an ecological study.
AB  - OBJECTIVE: To examine whether state-level spending on social and public health
      services is associated with lower rates of homicide in the USA. DESIGN:
      Ecological study. SETTING: USA. PARTICIPANTS: All states in the USA and the
      District of Columbia for which data were available (n=42). PRIMARY OUTCOME
      MEASURE: Homicide rates for each state were abstracted from the US Department of
      Justice Federal Bureau of Investigation's Uniform Crime Reporting. RESULTS: After
      adjusting for potential confounding variables, we found that every $10 000
      increase in spending per person living in poverty was associated with 0.87 fewer
      homicides per 100 000 population or approximately a 16% decrease in the average
      homicide rate (estimate=-0.87, SE=0.15, p<0.001). Furthermore, there was no
      significant effect in the quartile of states with the highest percentages of
      individuals living in poverty but significant effects in the quartiles of states
      with lower percentages of individuals living in poverty. CONCLUSIONS: Based on
      our findings, spending on social and public health services is associated with
      significantly lower homicide rates at the state level. Although we cannot infer
      causality from this research, such spending may provide promising avenues for
      homicide reduction in the USA, particularly among states with lower levels of
      poverty.

PMID- 29025832
TI  - Feasibility and acceptability of training community health workers in ear and
      hearing care in Malawi: a cluster randomised controlled trial.
AB  - OBJECTIVE: To assess the feasibility and acceptability of training community
      health workers (CHWs) in ear and hearing care, and their ability to identify
      patients with ear and hearing disorders. DESIGN: Cluster randomised controlled
      trial (RCT). SETTING: Health centres in Thyolo district, Malawi. PARTICIPANTS:
      Ten health centres participated, 5 intervention (29 CHWs) and 5 control (28
      CHWs). INTERVENTION: Intervention CHWs received 3 days of training in primary ear
      and hearing care, while among control CHWs, training was delayed for 6 months.
      Both groups were given a pretest that assessed knowledge about ear and hearing
      care, only the intervention group was given the posttest on the third day of
      training. The intervention group was given 1 month to identify patients with ear
      and hearing disorders in their communities, and these people were screened for
      hearing disorders by ear, nose and throat clinical specialists. OUTCOME MEASURES:
      Primary outcome measure was improvement in knowledge of ear and hearing care
      among CHWs after the training. Secondary outcome measures were number of patients
      with ear or hearing disorders identified by CHWs and number recorded at health
      centres during routine activities, and the perceived feasibility and
      acceptability of the intervention. RESULTS: The average overall correct answers
      increased from 55% to 68% (95% CI 65 to 71) in the intervention group (p<0.001).
      A total of 1739 patients with potential ear and hearing disorders were identified
      by CHWs and 860 patients attended the screening camps, of whom 400 had hearing
      loss (73 patients determined through bilateral fail on otoacoustic emissions, 327
      patients through audiometry). Where cause could be determined, the most common
      cause of ear and hearing disorders was chronic suppurative otitis media followed
      by impacted wax. The intervention was perceived as feasible and acceptable to
      implement. CONCLUSIONS: Training was effective in improving the knowledge of CHW
      in ear and hearing care in Malawi and allowing them to identify patients with ear
      and hearing disorders. This intervention could be scaled up to other CHWs in low
      income and middle-income countries. TRIAL REGISTRATION NUMBER: Pan African
      Clinical Trial Registry (201705002285194); Results.

PMID- 29025833
TI  - Prevalence and incidence of hypertension in the global HIV-infected population: a
      systematic review and meta-analysis protocol.
AB  - INTRODUCTION: Hypertension, representing one of the most frequent cardiovascular
      risk factors, is thought to increase in individuals living with HIV as well as in
      general population, but summarised global data on the topic are scarce. We
      conduct this systematic review and meta-analysis to assess the
      prevalence/incidence of hypertension in the global HIV-infected population.
      METHODS AND ANALYSIS: This review will include observational studies conducted
      among HIV-infected people, which reported prevalence/incidence of hypertension or
      enough data for its appraisal. We will consider published and unpublished studies
      from 1 January 2007 to 31 May 2017. Relevant records will be searched using
      PubMed/Medline, Global Index Medicus, Web of Science and EMBASE. Reference lists
      of eligible papers and relevant review articles will be screened. Two
      investigators will independently screen, select studies and extract data, with
      discrepancies resolved by consensus or by arbitration of a third investigator.
      Methodological quality of the included studies will be assessed using the scale
      developed by Hoy and colleagues. Funnel plots and Egger's test will be used to
      determine publication bias. The study-specific estimates will be pooled through a
      random-effects meta-analysis model to obtain an overall summary estimate. To keep
      the effect of studies with extremely small or extremely large estimates on the
      overall estimate to a minimum, the variance of the study-specific
      prevalence/incidence will be stabilised with the Freeman-Tukey single arcsine
      transformation. The heterogeneity will be evaluated by the chi2 test on
      Cochrane's Q statistic. Results will be presented by geographic region, income
      and antiretroviral therapy status. ETHICS AND DISSEMINATION: This study is based
      on published data; therefore, ethical approval is not a requirement. The final
      report of this study in the form of a scientific paper will be published in peer
      reviewed journals. TRIAL REGISTRATION NUMBER: CRD42016051684.

PMID- 29025834
TI  - Study protocol for a randomised controlled trial: harmonising optimal strategy
      for treatment of coronary artery stenosis - coronary intervention with next
      generation drug-eluting stent platforms and abbreviated dual antiplatelet therapy
      (HOST-IDEA) trial.
AB  - INTRODUCTION: We have recently seen the introduction of newer generation drug
      eluting stents with ultrathin struts that use advanced polymer technologies.
      However, the efficacy and safety of these newest stents have not yet been fully
      explored. In addition, there are still controversies over the optimal duration of
      dual antiplatelet therapy (DAPT) after stent implantation, particularly for
      ultrathin stents with the newest polymer technologies. METHODS AND ANALYSIS: The
      HOST-IDEA trial is a randomised, open-label, multicentre, non-inferiority trial
      and the first study to directly compare two of these ultrathin sirolimus-eluting
      stents: Orsiro stent with biodegradable polymer, and polymer-free Coroflex ISAR
      (CX-ISAR) stent. This study has a scheme of 2*2 factorial design according to the
      stent type and DAPT duration (3 vs 12 months). A total of 2152 patients will be
      randomised and stratified to demonstrate the non-inferiority of CX-ISAR to
      Orsiro, or of the abbreviated DAPT duration to the conventional 12 months (both
      in 1:1 ratio). For the comparison of stent type, the primary endpoint is target
      lesion failure (TLF), which is a composite of cardiac death, target vessel
      related myocardial infarction and clinically driven target lesion
      revascularisation. For the comparison of DAPT duration, the net adverse clinical
      event is the coprimary endpoint, which is defined as a composite of TLF,
      definite/probable stent thrombosis and major bleeding. ETHIC APPROVAL AND
      DISSEMINATION: All the institutions involved in this study are required to have
      ethical approval prior to patient enrolment. This multicentre study will recruit
      patients through competitive registration, but institutions that have not yet
      obtained ethical approvals have made it impossible to enrol patients in a
      centralised web database. The final results will be presented at relevant
      international conferences and will be materialised in the form of papers. TRIAL
      REGISTRATION NUMBER: NCT02601157; Pre-results.

PMID- 29025835
TI  - The CLIMB (Complex Lipids In Mothers and Babies) study: protocol for a
      multicentre, three-group, parallel randomised controlled trial to investigate the
      effect of supplementation of complex lipids in pregnancy, on maternal ganglioside
      status and subsequent cognitive outcomes in the offspring.
AB  - INTRODUCTION: Complex lipids are important constituents of the central nervous
      system. Studies have shown that supplementation with complex milk lipids (CML) in
      pregnancy may increase the level of fetal gangliosides (GA), with the potential
      to improve cognitive outcomes. METHODS AND ANALYSIS: We aim to recruit
      approximately 1500 pregnant women in the first trimester (11-14 weeks) and
      randomise them into one of the three treatment groups: standard maternal milk
      formulation, CML-enhanced maternal milk formulation or no maternal milk
      intervention with standard pregnancy advice (ie, the standard care). Maternal
      lifestyle and demographic data will be collected throughout the pregnancy, as
      well as biological samples (eg, blood, hair, urine, buccal smear, cord blood,
      cord and placenta samples). Data from standard obstetric care recorded in
      hospital maternity notes (eg, ultrasound reports, results of oral glucose
      tolerance test and pregnancy outcome data) will also be extracted. Postnatal
      follow-up will be at 6 weeks and 12 months of age, at which point infant
      cognitive development will be assessed (Bayley Scales of Infant Development I).
      ETHICS AND DISSEMINATION: This project was approved by the Ethics Committee of
      Chongqing Medical University. Dissemination of findings will take the form of
      publications in peer-reviewed journals and presentations at national and
      international conferences. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-16007700; Pre
      results.

PMID- 29025836
TI  - Assessment of potential predictors of calretinin and mesothelin to improve the
      diagnostic performance to detect malignant mesothelioma: results from a
      population-based cohort study.
AB  - OBJECTIVES: Mesothelin and calretinin are blood-based markers for malignant
      mesothelioma. The objective of this study was to analyse the markers in plasma
      samples from cancer-free men and to identify factors influencing their
      concentrations to minimise false-positive test results when using these markers
      for the early detection of malignant mesothelioma. SETTING: The present analyses
      used data and archived blood samples of the population-based Heinz Nixdorf Recall
      Study among elderly people collected from 2011 to 2014. PARTICIPANTS: A total of
      569 men (median age 70 years) without a malignant disease at the time of blood
      sampling were selected for these analyses. PRIMARY AND SECONDARY OUTCOME:
      Mesothelin and calretinin concentration in plasma samples. RESULTS: We observed
      24 mesothelin concentrations >=1.5 nM (specificity 95.8%, 95% CI 93.8% to 97.2%)
      and 34 calretinin concentrations >=1.0 ng/mL (specificity 94.0%, 95% CI 91.7% to
      95.7%). Only five men had both markers above these cut-offs. Renal dysfunction
      and hypertension were major predictors of elevated mesothelin in addition to age.
      Regarding calretinin, the effect of renal dysfunction was slightly weaker and
      hypertension was not associated with increased concentrations. However, a
      diagnosis of cancer after blood collection and bronchial asthma were associated
      with positive calretinin results. CONCLUSIONS: The combined determination of
      mesothelin and calretinin results in only few false-positive marker tests. Both
      markers are mainly influenced by renal dysfunction. The determination of cystatin
      C concentrations may be informative when interpreting the test results.

PMID- 29025837
TI  - Effects of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta
      cell function in children with newly diagnosed type 1 diabetes: protocol of a
      randomised controlled trial.
AB  - INTRODUCTION: Recent evidence has demonstrated that, among other factors,
      dysbiosis (imbalances in the composition and function of the gut microbiota) may
      be relevant in the development of type 1 diabetes (T1D). Thus, gut microbiota may
      be a target for improving outcomes in subjects with T1D. The aim of the study is
      to examine the effects of Lactobacillus rhamnosus GG and Bifidobacterium lactis
      Bb12 on beta-cell function in children with newly diagnosed T1D. METHODS AND
      ANALYSIS: A total of 96 children aged 8 to 17 years with newly diagnosed T1D,
      confirmed by clinical history and the presence of at least one positive
      autoantibody, will be enrolled in a double-blind, randomised, placebo-controlled
      trial in which they will receive L. rhamnosus GG and B. lactis Bb12 at a dose of
      109 colony-forming units or an identically appearing placebo, orally, once daily,
      for 6 months. The follow-up will be for 12 months. The primary outcome measures
      will be the area under the curve of the C-peptide level during 2-hour responses
      to a mixed meal. ETHICS AND DISSEMINATION: The Bioethics Committee approved the
      study protocol. The findings of this trial will be submitted to a peer-reviewed
      paediatric journal. Abstracts will be submitted to relevant national and
      international conferences. TRIAL REGISTRATION NUMBER: NCT03032354; Pre-results.

PMID- 29025838
TI  - Association between childhood allergic diseases, educational attainment and
      occupational status in later life: systematic review protocol.
AB  - INTRODUCTION: Childhood allergic diseases may prevent affected children from
      achieving their academic potential. Potential mechanisms include absence from
      school due to illness and medical appointments. Experience of symptoms in classes
      or leisure time, and stigma associated with visible signs and symptoms, including
      skin disease, requirements for medication during school time or the need for
      specific diets, may also contribute to reduced educational attainment. Studies
      have investigated the association between specific allergic diseases and
      educational attainment. The aim of this study is to systematically review the
      literature on allergic diseases, educational attainment and occupational status,
      and if possible, calculate meta-analytic summary estimates for the associations.
      METHODS: Systematic electronic searches in Medline, EMBASE, Cochrane, Cumulative
      Index to Nursing & Allied Health Literature (CINAHL), PsycINFO and education
      Resources Information Center (ERIC); hand search in reference lists of included
      papers and conference reports; search for unpublished studies in clinical trial
      registers and the New York Academy of Medicine Grey Literature Report; data
      extraction; and study quality assessment (Newcastle-Ottawa Scale) will be
      performed. ANALYSIS: Data will be summarised descriptively, and meta-analysis
      including meta-regression to explore sources of heterogeneities will be performed
      if possible. ETHICS AND DISSEMINATION: Dissemination in a peer-reviewed, open
      access, international scientific journal is planned. PROSPERO REGISTRATION
      NUMBER: CRD42017058036.

PMID- 29025839
TI  - Family attitudes, actions, decisions and experiences following implementation of
      deemed consent and the Human Transplantation (Wales) Act 2013: mixed-method study
      protocol.
AB  - INTRODUCTION: The Human Transplantation (Wales) Act 2013 (the Act) introduced a
      'soft opt-out' system of organ donation on 1 December 2015. Citizens are
      encouraged to make their organ donation decision known during their lifetime. In
      order to work, the Act and media campaign need to create a context, whereby organ
      donation becomes the norm, and create a mechanism for people to behave as
      intended (formally register their decision; consider appointing a representative;
      convey their donation decision to their families and friends or do nothing-deemed
      consent). In addition, family members/appointed representatives need to be able
      to put their own views aside to support the decision of their loved one. The aim
      of this study is to evaluate initial implementation, outcomes and impact on
      families and appointed representatives who were approached about organ donation
      during the first 18 months. METHODS AND ANALYSIS: Prospective mixed-method
      coproductive study undertaken with National Health Service Blood and Transplant
      (NHSBT), and multiple patient/public representatives. The study is designed to
      collect information on all cases who meet specified criteria (>=18 years,
      deceased person voluntarily resident in Wales and died in Wales or England) whose
      family were approached between 1 December 2015 and 31 June 2017). Data for
      analysis include: NHSBT routinely collected anonymised audit data on all cases;
      Specialist Nurse in Organ Donation (SNOD) completed anonymised form for all cases
      documenting their perception of the families' understanding of the Act, media
      campaign and outcome of the donation approach; questionnaires and depth
      interviews with any family member or appointed representative (minimum 50 cases).
      Additional focus groups and interviews with SNODs. Anonymised donation outcomes
      and registration activity reports for Wales provide additional context. ETHICS
      AND DISSEMINATION: Approved by NHSBT Research, Innovation and Technology Advisory
      Group on 23 October 2015; Wales Research Ethics Committee 5 (IRAS190066; Rec
      Reference 15/WA/0414) on 25 November 2015 and NHSBT R&D Committee (NHSBT ID: AP
      15-02) on 24 November 2015. REGISTRATION: The protocol is registered on the
      Health and Care Research Wales Clinical Research Portfolio. Study ID number
      34396, www.ukctg.nihr.ac.uk.

PMID- 29025840
TI  - A county-level cross-sectional analysis of positive deviance to assess multiple
      population health outcomes in Indiana.
AB  - OBJECTIVE: To test a positive deviance method to identify counties that are
      performing better than statistical expectations on a set of population health
      indicators. DESIGN: Quantitative, cross-sectional county-level secondary analysis
      of risk variables and outcomes in Indiana. Data are analysed using multiple
      linear regression to identify counties performing better or worse than expected
      given traditional risk indicators, with a focus on 'positive deviants' or
      counties performing better than expected. PARTICIPANTS: Counties in Indiana
      (n=92) constitute the unit of analysis. MAIN OUTCOME MEASURES: Per cent adult
      obesity, per cent fair/poor health, low birth weight per cent, per cent with
      diabetes, years of potential life lost, colorectal cancer incidence rate and
      circulatory disease mortality rate. RESULTS: County performance that outperforms
      expectations is for the most part outcome specific. But there are a few counties
      that performed particularly well across most measures. CONCLUSIONS: The positive
      deviance approach provides a means for state and local public health departments
      to identify places that show better health outcomes despite demographic, social,
      economic or behavioural disadvantage. These places may serve as case studies or
      models for subsequent investigations to uncover best practices in the face of
      adversity and generalise effective approaches to other areas.

PMID- 29025841
TI  - Neighbourhood characteristics and mental disorders in three Chinese cities:
      multilevel models from the World Mental Health Surveys.
AB  - OBJECTIVES: The rapid growth of urban areas in China in the past few decades has
      introduced profound changes in family structure and income distribution that
      could plausibly affect mental health. Although multilevel studies of the
      influence of area-level socioeconomic factors on mental health have become more
      common in other parts of the world, a study of this sort has not been carried out
      in Chinese cities. Our objectives were to examine the associations of two key
      neighbourhood-level variables-median income and percentage of married individuals
      living in the neighbourhood-with mental disorders net of individual-level income
      and marital status in three Chinese cities. SETTING: Household interviews in
      Beijing, Shanghai and Shenzhen, PRC, as part of the cross-sectional World Mental
      Health Surveys. PARTICIPANTS: 4072 men and women aged 18-88 years. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Lifetime and past-year internalising and
      externalising mental disorders. RESULTS: Each one-point increase in neighbourhood
      level percentage of married residents was associated with a 1% lower odds of
      lifetime (p=0.024) and 2% lower odds of past-year (p=0.008) individual-level
      externalising disorder, net of individual-level marital status. When split into
      tertiles, individuals living in neighbourhoods in the top tertile of percentage
      of married residents had 54% lower odds of a past-year externalising disorder
      (OR=0.46, 95% CI: 0.24 to 0.87) compared with those in the bottom tertile.
      Neighbourhood-level marital status was not statistically associated with either
      lifetime or past-year internalising disorders. Neighbourhood-level income was not
      statistically associated with odds of either internalising or externalising
      disorders. CONCLUSIONS: The proportion of married residents in respondents'
      neighbourhoods was significantly inversely associated with having externalising
      mental disorders in this sample of Chinese cities. Possible mechanisms for this
      finding are discussed and related to social causation, social selection and
      social control theories. Future work should examine these relationships
      longitudinally.

PMID- 29025842
TI  - Discrepancies between ClinicalTrials.gov recruitment status and actual trial
      status: a cross-sectional analysis.
AB  - OBJECTIVES: To determine the accuracy of the recruitment status listed on
      ClinicalTrials.gov as compared with the actual trial status. DESIGN: Cross
      sectional analysis. SETTING: Random sample of interventional phase 2-4 clinical
      trials registered between 2010 and 2012 on ClinicalTrials.gov. PRIMARY OUTCOME
      MEASURE: For each trial which was listed within ClinicalTrials.gov as ongoing,
      two investigators performed a comprehensive literature search for evidence that
      the trial had actually been completed. For each trial listed as completed or
      terminated early by ClinicalTrials.gov, we compared the date that the trial was
      actually concluded with the date the registry was updated to reflect the study's
      conclusion status. RESULTS: Among the 405 included trials, 92 had a registry
      status indicating that study activity was either ongoing or the recruitment
      status was unknown. Of these, published results were available for 34 (37%).
      Among the 313 concluded trials, the median delay between study completion and a
      registry update reflecting that the study had ended was 141 days (IQR 48-419),
      with delays of over 1 year present for 29%. In total, 125 trials (31%) either had
      a listed recruitment status which was incorrect or had a delay of more than 1
      year between the time the study was concluded and the time the registry
      recruitment status was updated. CONCLUSIONS: At present, registry recruitment
      status information in ClinicalTrials.gov is often outdated or wrong. This
      inaccuracy has implications for the ability of researchers to identify completed
      trials and accurately characterise all available medical knowledge on a given
      subject.

PMID- 29025843
TI  - Preparing the prescription: a review of the aim and measurement of social
      referral programmes.
AB  - OBJECTIVE: Our aim is to review, and qualitatively evaluate, the aims and
      measures of social referral programmes. Our first objective is to identify the
      aims of social referral initiatives. Our second objective is to identify the
      measures used to evaluate whether the aims of social referral were met. DESIGN:
      Literature review. BACKGROUND: Social referral programmes, also called social
      prescribing and emergency case referral, link primary and secondary healthcare
      with community services, often under the guise of decreasing health system costs.
      METHOD: Following the PRISMA guidelines, we undertook a literature review to
      address that aim. We searched in five academic online databases and in one online
      non-academic search engine, including both academic and grey literature, for
      articles referring to 'social prescribing' or 'community referral'. RESULTS: We
      identified 41 relevant articles and reports. After extracting the aims, measures
      and type of study, we found that most social referral programmes aimed to address
      a wide variety of system and individual health problems. This included cost
      savings, resource reallocation and improved mental, physical and social well
      being. Across the 41 studies and reports, there were 154 different kinds of
      measures or methods of evaluation identified. Of these, the most commonly used
      individual measure was the Warwick-Edinburgh Mental Well-being Scale, used in
      nine studies and reports. CONCLUSIONS: These inconsistencies in aims and measures
      used pose serious problems when social prescribing and other referral programmes
      are often advertised as a solution to health services-budgeting constraints, as
      well as a range of chronic mental and physical health conditions. We recommend
      researchers and local community organisers alike to critically evaluate for whom,
      where and why their social referral programmes 'work'.

PMID- 29025844
TI  - Investigating Canadian parents' HPV vaccine knowledge, attitudes and behaviour: a
      study protocol for a longitudinal national online survey.
AB  - INTRODUCTION: Human papillomavirus (HPV), a sexually transmitted infection, can
      cause anogenital warts and a number of cancers. To prevent morbidity and
      mortality, three vaccines have been licensed and are recommended by Canada's
      National Advisory Committee on Immunisation (for girls since 2007 and boys since
      2012). Nevertheless, HPV vaccine coverage in Canada remains suboptimal in many
      regions. This study will be the first to concurrently examine the correlates of
      HPV vaccine decision-making in parents of school-aged girls and boys and evaluate
      changes in parental knowledge, attitudes and behaviours over time. METHODS AND
      ANALYSIS: Using a national, online survey utilising theoretically driven
      constructs and validated measures, this study will identify HPV vaccine coverage
      rates and correlates of vaccine decision-making in Canada at two time points
      (August-September 2016 and June-July 2017). 4606 participants will be recruited
      to participate in an online survey through a market research and polling firm
      using email invitations. Data cleaning methods will identify inattentive or
      unmotivated participants. ETHICS AND DISSEMINATION: The study received research
      ethics board approval from the Research Review Office, Integrated Health and
      Social Services University Network for West-Central Montreal (CODIM-FLP-16-219).
      The study will adopt a multimodal approach to disseminate the study's findings to
      researchers, clinicians, cancer and immunisation organisations and the public in
      Canada and internationally.

PMID- 29025845
TI  - A multicentre randomised controlled trial assessing whether MRI-targeted biopsy
      is non-inferior to standard transrectal ultrasound guided biopsy for the
      diagnosis of clinically significant prostate cancer in men without prior biopsy:
      a study protocol.
AB  - INTRODUCTION: The classical pathway for the diagnosis of prostate cancer is
      transrectal ultrasound-guided (TRUS) biopsy of the prostate initiated on the
      basis of a raised prostate-specific antigen (PSA). An alternative pathway is to
      perform multi-parametricMRI (MPMRI) to localise cancer and to use this
      information to influence the decision for, and conduct of, a subsequent biopsy,
      known as an MPMRI-targeted biopsy. An MPMRI pathway has been shown to detect a
      similar or greater amount of clinically significant cancer as TRUS biopsy but has
      several advantages, including the potential to biopsy fewer men with fewer cores.
      METHODS: This is a pragmatic, international, multicentre, parallel group
      randomised study in which men are allocated in a 1:1 ratio to an MPMRI or TRUS
      biopsy pathway. This study will assess whether an MPMRI-targeted biopsy approach
      is non-inferior to a standard TRUS biopsy approach in the diagnosis of clinically
      significant cancer.Men in the MRI arm will undergo targeted biopsy of suspicious
      areas only and no biopsy will be carried out if the MRI is non-suspicious. Men in
      the TRUS biopsy will undergo a standard 10-12-core TRUS biopsy. The main
      inclusion criteria are a serum PSA <=20 ng/mL, a digital rectal examination
      finding of T2 or less and no prior prostate biopsy.The primary outcome is the
      proportion of men with clinically significant cancer detected. A sample size of
      at least 470 patients is required. Key secondary outcomes include the proportion
      of clinically insignificant cancer detected. ETHICS AND DISSEMINATION: Ethical
      approval was obtained from the National Research Ethics Committee East Midlands,
      Leicester (15/EM/0188). Results of this study will be disseminated through
      national and international papers. The participants and relevant patient support
      groups will be informed about the results of the study. REGISTRATION DETAILS:
      NCT02380027; Pre-results.

PMID- 29025846
TI  - Cohort profile for the MASTERMIND study: using the Clinical Practice Research
      Datalink (CPRD) to investigate stratification of response to treatment in
      patients with type 2 diabetes.
AB  - PURPOSE: This is a retrospective cohort study using observational data from
      anonymised primary care records. We identify and extract all patients with type 2
      diabetes and associated clinical data from the Clinical Practice Research
      Datalink (CPRD) to inform models of disease progression and stratification of
      treatment. PARTICIPANTS: Data were extracted from CPRD on 8 August 2016. The
      initial data set contained all patients (n=313 485) in the database who had
      received a type 2 diabetes medication. Criteria were applied to identify and
      exclude those with type 1 diabetes, polycystic ovarian syndrome or other forms of
      diabetes (n=40 204), and for data quality control (n=12). We identified 251 338
      patients for inclusion in future analyses of diabetes progression and treatment
      response. FINDINGS TO DATE: For 6-month response to treatment, measured by change
      in glycated haemoglobin (HbA1c), we have 91 765 patients with 119 785 treatment
      response episodes. The greatest impact on reduction of HbA1c occurs with first
      line and second-line treatments, metformin and sulfonylurea. Patients moving to
      third-line treatments tend to have greater weights and higher body mass index. We
      have investigated the impact of non-adherence to commonly used glucose-lowering
      medications on HbA1c. For baseline-adjusted HbA1c change over 1 year, non
      adherent patients had lower HbA1c reductions than adherent patients, with mean
      and 95% CI of -4.4 (-4.7 to -4.0) mmol/mol (-0.40 (-0.43 to -0.37) %). FUTURE
      PLANS: Findings from studies using these data will help inform future treatment
      plans and guidelines. Additional data are added with updates from CPRD. This will
      increase the numbers of patients on newer medications and add more data on those
      already receiving treatment. There are several ongoing studies investigating
      different hypotheses regarding differential response to treatment and progression
      of diabetes. For side effects, links to Hospital Episode Statistics data, where
      severe events such as hypoglycaemia will be recorded, will also be explored.

PMID- 29025847
TI  - Exploring the role of the nurse manager in supporting point-of-care nurses'
      adoption of electronic health records: protocol for a qualitative research study.
AB  - INTRODUCTION: An increasing number of electronic health record (EHR) systems have
      been implemented in clinical practice environments where nurses work. Findings
      from previous studies have found that a number of intended benefits of the
      technology have not yet been realised to date, partially due to poor system
      adoption among health professionals such as nurses. Previous studies have
      suggested that nurse managers can support the effective adoption and use of the
      technology by nurses. However, no known studies have identified what role nurse
      managers have in supporting technology adoption, nor the specific strategies that
      managers can employ to support their staff. Therefore, the purpose of this
      research is to better understand the role of the nurse manager in point-of-care
      nurses' use of EHRs, and to identify strategies that may be effective in
      supporting clinical adoption. METHODS AND ANALYSIS: This study will use a
      qualitative descriptive design. Interviews with both nurse managers and point-of
      care nursing staff will be conducted in a Canadian mental health and addiction
      healthcare organisation where an EHR has been implemented. A semistructured
      interview guide will be used, and interviews will be audio recorded. Transcripts
      will be analysed using a directed content analysis technique. Strategies to
      ensure the trustworthiness of the data analysis procedure and findings will be
      employed. ETHICS AND DISSEMINATION: Ethical approval for this study has been
      obtained. Dissemination strategies may include a paper submission to a peer
      reviewed journal, a conference submission and meetings to share findings with the
      study site leadership team. Findings from this research will be used to inform a
      future study which aims to assess levels of competencies and perform a
      psychometric analysis of the Nursing Informatics Competency Assessment for the
      Nurse Leader instrument in a Canadian context.

PMID- 29025848
TI  - Ectopic pregnancy: exploration of its global research architecture using density
      equalising mapping and socioeconomic benchmarks.
AB  - OBJECTIVE: About 2% of all pregnancies are complicated by the implantation of the
      zygote outside the uterine cavity and termed ectopic pregnancy. Whereas a
      multitude of guidelines exists and related research is constantly growing, no
      thorough assessment of the global research architecture has been performed yet.
      Hence, we aim to assess the associated scientific activities in relation to
      geographical and chronological developments, existing research networks and
      socioeconomic parameters. DESIGN: Retrospective, descriptive study. SETTING: On
      the basis of the NewQIS platform, scientometric methods were combined with novel
      visualising techniques such as density-equalising mapping to assess the
      scientific output on ectopic pregnancy. Using the Web of Science, we identified
      all related entries from 1900 to 2012. RESULTS: 8040 publications were analysed.
      The USA and the UK were dominating the field in regard to overall research
      activity (2612 and 723 publications), overall citation numbers and country
      specific H-Indices (US: 80, UK: 42). Comparison to economic power of the most
      productive countries demonstrated that Israel invested more resources in ectopic
      pregnancy-related research than other nations (853.41 ectopic pregnancy-specific
      publications per 1000 billlion US$ gross domestic product (GDP)), followed by the
      UK (269.97). Relation to the GDP per capita index revealed 49.3 ectopic pregnancy
      specific publications per US$1000 GDP per capita for the USA in contrast to 17.31
      for the UK. Semiqualitative indices such as country-specific citation rates
      ranked Switzerland first (24.7 citations per ectopic pregnancy-specific
      publication), followed by the Scandinavian countries Finland and Sweden. Low
      income countries did not exhibit significant research activities. CONCLUSIONS:
      This is the first in-depth analysis of global ectopic pregnancy research since
      1900. It offers unique insights into the global scientific landscape. Besides the
      USA and the UK, Scandinavian countries and Switzerland can also be regarded as
      leading nations with regard to their relative socioeconomic input.

PMID- 29025852
TI  - Correction: Attitudes and perceptions of GPs and community pharmacists towards
      their role in the prevention of bisphosphonate-related osteonecrosis of the jaw:
      a qualitative study in the North East of England.

PMID- 29025849
TI  - The association between adverse childhood experiences and traumatic brain
      injury/concussion in adulthood: A scoping review protocol.
AB  - INTRODUCTION: Exposure to adverse childhood experiences (ACEs) is a significant
      risk factor for physical and mental illnesses later in life. Concussion or
      traumatic brain injury is a challenging condition where preinjury factors may
      interact to affect recovery. The association between ACEs and traumatic brain
      injury/concussion is not well mapped in any previous reviews of the literature.
      Using a scoping review methodology, the research question that will be addressed
      is: what is known from the existing literature about the association between ACEs
      and traumatic brain injury/concussion in adults? METHODS AND ANALYSIS: The
      methodological frameworks outlined by Arksey and O'Malley and Levac et al will be
      used. All original studies in English published since 2007 investigating ACEs and
      traumatic brain injury/concussion outcomes will be included with no limitations
      on study type. Literature search strategies will be developed using medical
      subject headings and text words related to ACEs and traumatic brain
      injury/concussions. Multiple electronic databases will be searched. Two
      independent reviewers will screen titles and abstracts for full-text review and
      full texts for final inclusion. Two independent reviewers will extract data on
      study characteristics for ACE exposure and traumatic brain injury/concussion
      outcomes. Extracted data will be summarised quantitatively using numerical counts
      and qualitatively using thematic analysis. DISSEMINATION: This review will
      identify knowledge gaps on the associations between ACEs and traumatic brain
      injury/concussion and promote further research. Knowledge translation will occur
      throughout the review process with dissemination of project findings to
      stakeholders at the local, national and international levels.

PMID- 29025853
TI  - Concomitant administration of methotrexate does not improve efficacy of intra
      articular joint injections in patients with oligoarticular juvenile idiopathic
      arthritis.

PMID- 29025851
TI  - Investigating Bordetella pertussis colonisation and immunity: protocol for an
      inpatient controlled human infection model.
AB  - INTRODUCTION: We summarise an ethically approved protocol for the development of
      an experimental human challenge colonisation model. Globally Bordetella pertussis
      is one of the leading causes of vaccine-preventable death. Many countries have
      replaced whole cell vaccines with acellular vaccines over the last 20 years
      during which pertussis appears to be resurgent in a number of countries in the
      developed world that boast high immunisation coverage. The acellular vaccine
      provides relatively short-lived immunity and, in contrast to whole cell vaccines,
      may be less effective against colonisation and subsequent transmission. To
      improve vaccine strategies, a greater understanding of human B. pertussis
      colonisation is required. This article summarises a protocol and does not contain
      any results. METHODS AND ANALYSIS: A controlled human colonisation model will be
      developed over two phases. In phase A, a low dose of the inoculum will be given
      intranasally to healthy participants. This dose will be escalated or de-escalated
      until colonisation is achieved in approximately 70% (95% CI 47% to 93%) of the
      exposed volunteers without causing disease. The colonisation period, shedding and
      exploratory immunology will be assessed during a 17-day inpatient stay and follow
      up over 1 year. The dose of inoculum that achieves 70% colonisation will then be
      confirmed in phase B, comparing healthy participants exposed to B. pertussis with
      a control group receiving a sham inoculum. ETHICS AND DISSEMINATION: This study
      has been approved by the ethical committee reference: 17/SC/0006, 24 February
      2017. Findings will be published in peer-reviewed open access journals as soon as
      possible.

PMID- 29025850
TI  - Protocol for a pilot, randomised, double-blinded, placebo-controlled trial of
      prophylactic use of tranexamic acid for preventing postpartum haemorrhage (TAPPH
      1).
AB  - INTRODUCTION: Postpartum haemorrhage (PPH) is the leading cause of maternal
      morbidity and mortality worldwide. Despite the availability of multiple
      uterotonic agents, the incidence of PPH continues to rise. Tranexamic acid (TXA)
      has been shown to be a safe, effective and inexpensive therapeutic option for the
      treatment of PPH, however, its use prophylactically in mitigating the risk of PPH
      is unknown. This pragmatic randomised prospective trial assesses the feasibility
      and safety of administering TXA at the time of delivery for the prevention of
      PPH. METHODS AND ANALYSIS: A pilot pragmatic randomised double-blinded placebo
      controlled trial will be performed. 58 singleton parturients at term >32 weeks,
      undergoing either spontaneous vaginal delivery, or caesarean section will be
      randomised to receive 1 g of TXA or placebo (0.9% saline) intravenously. The
      primary outcome assessed will be the feasibility of administrating TXA, along
      with collecting data regarding safety of drug administration. The groups will
      also be analysed on efficacy of mitigating the onset of PPH and clinically
      relevant variables. Demographic, feasibility, safety and clinical endpoints will
      be summarised and the appropriate measures of central tendency and dispersion
      will be presented. ETHICS AND DISSEMINATION: This protocol was approved by the
      Sunnybrook Health Sciences Centre Research Ethics Board (number: 418-2016). The
      results will be disseminated in a peer-reviewed journal and at scientific
      meetings. TRIAL REGISTRATION NUMBER: NCT03069859; Pre-results.

PMID- 29025854
TI  - How to use... Hip examination and ultrasound in newborns.
AB  - Developmental dysplasia of the hip (DDH) ranges from a clinically detectable
      dislocation of the hip to radiologically diagnosed hip abnormalities. It is
      caused by both antenatal and postnatal factors. The Neonatal and Infant Physical
      Examination Screening Programme recommends that newborns should undergo a hip
      ultrasound (USS) when risk factor or clinical features suggestive of DDH are
      present. The aim of hip ultrasonography is to detect DDH early and prevent late
      complications through early treatment. Here, we discuss how to use hip
      examination and USS in newborns.

PMID- 29025855
TI  - Management of children and young people with an acute decrease in conscious level
      (RCPCH guideline update 2015).

PMID- 29025856
TI  - Paediatric intensive care nurses report higher empathy but also higher burnout
      than other health professionals.

PMID- 29025857
TI  - Endocrine side effects of cancer immunotherapy.
AB  - Immune checkpoint inhibitors have recently become a cornerstone for the treatment
      of different advanced cancers. These drugs, represented mainly by monoclonal
      antibodies anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell
      death protein-1 (PD-1) and anti-PD-1 ligand molecules (PD-L1 and L2), have the
      ability to reactivate the immune system against tumor cells, but can also trigger
      a myriad of autoimmune side effects, termed immune-related adverse events
      (irAEs). In particular, there are a number of endocrine-related irAEs. Current
      data from clinical trials show increased incidence of hypophysitis with CTLA4
      inhibition and thyroid dysfunction with PD-(L)1 blockade. In addition, a few
      cases of type 1 diabetes mellitus and primary adrenal insufficiency have been
      reported. We discuss the incidence, clinical manifestations, diagnosis and
      management of immune-related endocrinopathies in this highly complex context of
      oncological patients in need of immunotherapies.

PMID- 29025859
TI  - Erratum. Direct Substrate Delivery Into Mitochondrial Fission-Deficient
      Pancreatic Islets Rescues Insulin Secretion. Diabetes 2017;66:1247-1257.

PMID- 29025858
TI  - Histone Modifications Regulate the Developmental Expression of Human Hepatic UDP
      Glucuronosyltransferase 1A1.
AB  - Human UDP-glucuronosyltransferase 1A1 (UGT1A1) is a unique enzyme involved in
      bilirubin conjugation. We previously characterized the hepatic expression of
      transcription factors affecting UGT1A1 expression during development.
      Accordingly, in this study, we characterized the ontogenetic expression of
      hepatic UGT1A1 from the perspective of epigenetic regulation. We observed
      significant histone-3-lysine-4 dimethylation (H3K4me2) enrichment in the adult
      liver and histone-3-lysine-27 trimethylation (H3K27me3) enrichment in the fetal
      liver, indicating that dynamic alterations of histone methylation were associated
      with ontogenetic UGT1A1 expression. We further showed that the transcription
      factor hepatocyte nuclear factor 1alpha (HNF1A) affects histone modifications
      around the UGT1A1 locus. In particular, we demonstrated that by recruiting HNF1A
      the cofactors mixed-lineage leukemia 1, the transcriptional coactivator p300, and
      nuclear receptor coactivator 6 aggregate at the UGT1A1 promoter, thereby
      regulating histone modifications and subsequent UGT1A1 expression. In this study,
      we proposed new ideas for the developmental regulation of metabolic enzymes via
      histone modifications, and our findings will potentially contribute to the
      development of age-specific therapies.

PMID- 29025860
TI  - Negative Regulation of TRPA1 by AMPK in Primary Sensory Neurons as a Potential
      Mechanism of Painful Diabetic Neuropathy.
AB  - AMPK is a widely expressed intracellular energy sensor that monitors and
      modulates energy expenditure. Transient receptor potential ankyrin 1 (TRPA1)
      channel is a widely recognized chemical and thermal sensor that plays vital roles
      in pain transduction. In this study, we discovered a functional link between AMPK
      and TRPA1 in dorsal root ganglion (DRG) neurons, in which AMPK activation rapidly
      resulted in downregulation of membrane-associated TRPA1 and its channel activity
      within minutes. Treatment with two AMPK activators, metformin or AICAR, inhibited
      TRPA1 activity in DRG neurons by decreasing the amount of membrane-associated
      TRPA1. Metformin induced a dose-dependent inhibition of TRPA1-mediated calcium
      influx. Conversely, in diabetic db/db mice, AMPK activity was impaired in DRG
      neurons, and this was associated with a concomitant increase in membrane
      associated TRPA1 and mechanical allodynia. Notably, these molecular and
      behavioral changes were normalized following treatment with AMPK activators.
      Moreover, high-glucose exposure decreased activated AMPK levels and increased
      agonist-evoked TRPA1 currents in cultured DRG neurons, and these effects were
      prevented by treatment with AMPK activators. Our results identify AMPK as a
      previously unknown regulator of TRPA1 channels. AMPK modulation of TRPA1 could
      thus serve as an underlying mechanism and potential therapeutic molecular target
      in painful diabetic neuropathy.

PMID- 29025861
TI  - Multiple indicators of ill health are evident in people with psychosis.

PMID- 29025863
TI  - Are rising admission thresholds good medicine?

PMID- 29025862
TI  - Developing digital interventions for people living with serious mental illness:
      perspectives from three mHealth studies.
AB  - The rapidly expanding field of mobile health (mHealth) seeks to harness
      increasingly affordable and ubiquitous mobile digital technologies including
      smartphones, tablets, apps and wearable devices to enhance clinical care.
      Accumulating evidence suggests that mHealth interventions are increasingly being
      adopted and valued by people living with serious mental illnesses such as
      schizophrenia and bipolar disorder, as a means of better understanding and
      managing their condition. We draw on experiences from three geographically and
      methodologically distinct mHealth studies to provide a pragmatic overview of the
      key challenges and considerations relating to the process of developing digital
      interventions for this population.

PMID- 29025865
TI  - Publisher's Note: Rho differentially regulates the Hippo pathway by modulating
      the interaction between Amot and Nf2 in the blastocyst. Development doi:
      10.1242/dev.157917.

PMID- 29025864
TI  - Pre-emptive ice cube cryotherapy for reducing pain from local anaesthetic
      injections for simple lacerations: a randomised controlled trial.
AB  - OBJECTIVE: Subcutaneous local anaesthetic injection can be painful to patients in
      the ED. We evaluated the effect of cryotherapy by application of an ice cube to
      the injection site prior to injection in patients with simple lacerations.
      METHODS: We conducted a prospective, randomised, controlled trial in consented
      patients with simple lacerations needing primary repair at a single emergency
      centre from April to July 2016. We randomly assigned patients undergoing repair
      for simple lacerations to either the cryotherapy group or the control group
      (standard care; no cryotherapy or other pretreatment of the injection site). In
      cryotherapy group subjects, we applied an ice cube (size: 1.5*1.5*1.5 cm) placed
      inside a sterile glove on the wound at the anticipated subcutaneous lidocaine
      injection site for 2 min prior to injection. The primary outcome was a subjective
      numeric rating (0-10 scale) of the perceived pain from the subcutaneous local
      anaesthetic injections. Secondary outcomes were (a) perceived pain on a numeric
      scale for cryotherapy itself, that is, pain from contact of the ice cube/glove
      with the skin and (b) the rate of complications after primary laceration repair.
      RESULTS: Fifty patients were enrolled, consented and randomised, with 25 in the
      cryotherapy group and 25 in the control group. The numeric rating scale for
      subcutaneous anaesthetic injections was median, IQR, 95% CI 2.0 (1 to 3.5), 1.81
      to 3.47, respectively, in the cryotherapy group and 5.0 (3 to 7), 3.91 to 6.05 in
      the control group (Mann-Whitney U=147.50, p=0.001). No wound complications
      occurred in either group. The numeric rating scale for cryotherapy itself was
      median, IQR, 95% CI: 2.0 (1 to 3.5), 1.90 to 3.70. CONCLUSION: Pre-emptive
      topical injection site cryotherapy lasting 2 min before subcutaneous local
      anaesthetic injections can significantly reduce perceived pain from subcutaneous
      local anaesthetic injections in patients presenting for simple laceration repair.
      TRIAL REGISTRATION NUMBER: KCT0001990.

PMID- 29025866
TI  - Declining levels of functionally specialized synaptic proteins in plasma neuronal
      exosomes with progression of Alzheimer's disease.
AB  - Interactions of the presynaptic proteins, neuronal pentraxin 2 (NPTX2) and
      neurexin 2alpha (NRXN2alpha), with their respective postsynaptic functional
      partners, GluA4-containing glutamate (AMPA4) receptor and neuroligin 1 (NLGN1),
      enhance excitatory synaptic activity in some areas of the hippocampus and
      cerebral cortex. As early damage of such excitatory circuits in the brain tissues
      of participants with Alzheimer's disease (AD) correlates with cognitive losses,
      plasma neuron-derived exosome (NDE) levels of these 2 pairs of specialized
      synaptic proteins were quantified to assess their biomarker characteristics. The
      NDE contents of all 4 proteins were decreased significantly in AD dementia ( n =
      46), and diminished levels of AMPA4 and NLGN1 correlated with the extent of
      cognitive loss. In a preclinical period, 6-11 yr before the onset of dementia,
      the NDE levels of all but NPTX2 were significantly lower than those of matched
      controls, and levels of all proteins declined significantly with the development
      of dementia. Reductions in NDE levels of these specialized excitatory synaptic
      proteins may therefore be indicative of the extent of cognitive loss and may
      reflect progression of the severity of AD.-Goetzl, E. J., Abner, E. L., Jicha, G.
      A., Kapogiannis, D., Schwartz, J. B. Declining levels of functionally specialized
      synaptic proteins in plasma neuronal exosomes with progression of Alzheimer's
      disease.

PMID- 29025867
TI  - Threading the biophysics of mammalian Slo1 channels onto structures of an
      invertebrate Slo1 channel.
AB  - For those interested in the machinery of ion channel gating, the Ca2+ and voltage
      activated BK K+ channel provides a compelling topic for investigation, by virtue
      of its dual allosteric regulation by both voltage and intracellular Ca2+ and
      because its large-single channel conductance facilitates detailed kinetic
      analysis. Over the years, biophysical analyses have illuminated details of the
      allosteric regulation of BK channels and revealed insights into the mechanism of
      BK gating, e.g., inner cavity size and accessibility and voltage sensor-pore
      coupling. Now the publication of two structures of an Aplysia californica BK
      channel-one liganded and one metal free-promises to reinvigorate functional
      studies and interpretation of biophysical results. The new structures confirm
      some of the previous functional inferences but also suggest new perspectives
      regarding cooperativity between Ca2+-binding sites and the relationship between
      voltage- and Ca2+-dependent gating. Here we consider the extent to which the two
      structures explain previous functional data on pore-domain properties, voltage
      sensor motions, and divalent cation binding and activation of the channel.

PMID- 29025868
TI  - In situ visualization of glucocerebrosidase in human skin tissue: zymography
      versus activity-based probe labeling.
AB  - Epidermal beta-glucocerebrosidase (GBA1), an acid beta-glucosidase normally
      located in lysosomes, converts (glucosyl)ceramides into ceramides, which is
      crucial to generate an optimal barrier function of the outermost skin layer, the
      stratum corneum (SC). Here we report on two developed in situ methods to localize
      active GBA in human epidermis: i) an optimized zymography method that is less
      labor intensive and visualizes enzymatic activity with higher resolution than
      currently reported methods using either substrate 4-methylumbelliferyl-beta-D
      glucopyranoside or resorufin-beta-D-glucopyranoside; and ii) a novel technique to
      visualize active GBA1 molecules by their specific labeling with a fluorescent
      activity-based probe (ABP), MDW941. The latter method pro-ved to be more robust
      and sensitive, provided higher resolution microscopic images, and was less prone
      to sample preparation effects. Moreover, in contrast to the zymography substrates
      that react with various beta-glucosidases, MDW941 specifically labeled GBA1. We
      demonstrate that active GBA1 in the epidermis is primarily located in the
      extracellular lipid matrix at the interface of the viable epidermis and the lower
      layers of the SC. With ABP-labeling, we observed reduced GBA1 activity in 3D
      cultured skin models when supplemented with the reversible inhibitor,
      isofagomine, irrespective of GBA expression. This inhibition affected the SC
      ceramide composition: MS analysis revealed an inhibitor-dependent increase in the
      glucosylceramide:ceramide ratio.

PMID- 29025869
TI  - Regulation of TG accumulation and lipid droplet morphology by the novel TLDP1 in
      Aurantiochytrium limacinum F26-b.
AB  - Thraustochytrids are marine single-cell protists that produce large amounts of
      PUFAs, such as DHA. They accumulate PUFAs in lipid droplets (LDs), mainly as
      constituent(s) of triacylglycerol (TG). We identified a novel protein in the LD
      fraction of Aurantiochytrium limacinum F26-b using 2D-difference gel
      electrophoresis. The protein clustered with orthologs of thraustochytrids;
      however, the cluster was evolutionally different from known PAT family proteins
      or plant LD protein; thus, we named it thraustochytrid-specific LD protein 1
      (TLDP1). TLDP1 surrounded LDs when expressed as a GFP-tagged form. Disruption of
      the tldp1 gene decreased the content of TG and number of LDs per cell; however,
      irregular and unusually large LDs were generated in tldp1-deficient mutants.
      Although the level of TG synthesis was unchanged by the disruption of tldp1, the
      level of TG degradation was higher in tldp1-deficient mutants than in the WT.
      These phenotypic abnormalities in tldp1-deficient mutants were restored by the
      expression of tldp1 These results indicate that TLDP1 is a thraustochytrid
      specific LD protein and regulates the TG accumulation and LD morphology in A.
      limacinum F26-b.

PMID- 29025870
TI  - Genetic landscape of interactive effects of HLA-DRB1 alleles on susceptibility to
      ACPA(+) rheumatoid arthritis and ACPA levels in Japanese population.
AB  - BACKGROUND: HLA-DRB1 is the strongest susceptibility gene to rheumatoid arthritis
      (RA). HLA-DRB1 alleles showed significant non-additive and interactive effects on
      susceptibility to RA in the European population, but these effects on RA
      susceptibility should vary between populations due to the difference in allelic
      distribution. Furthermore, non-additive or interactive effects on the phenotypes
      of RA are not fully known. We evaluated the non-additive and interactive effects
      of HLA-DRB1 alleles on RA susceptibility and anticitrullinated protein/peptide
      antibody (ACPA) levels in Japanese patients. METHODS: A total of 5581 ACPA(+) RA
      and 19 170 controls were genotyped or imputed for HLA-DRB1 alleles. Logistic
      regression analysis was performed for both allelic non-additive effects and
      interactive effects of allelic combinations. The significant levels were set by
      Bonferroni's correction. A total of 4371 ACPA(+) RA were analysed for ACPA
      levels. RESULTS: We obtained evidence of non-additive and interactive effects of
      HLA-DRB1 on ACPA(+) RA susceptibility (p=2.5*10-5 and 1.5*10-17, respectively).
      Multiple HLA-DRB1 alleles including HLA-DRB1*04:05, the most common
      susceptibility allele in the Japanese, showed significant non-additive effects
      (p<=0.0043). We identified multiple allelic combinations with significant
      interactive effects including a common combination with the European population
      as well as novel combinations. Additional variance of ACPA(+) RA susceptibility
      could be explained substantially by heterozygote dominance or interactive
      effects. We did not find evidence of non-additive and interactive effects on
      levels of ACPA. CONCLUSION: HLA allelic non-additive and interactive effects on
      ACPA(+) RA susceptibility were observed in the Japanese population. The allelic
      non-additive and interactive effects depend on allelic distribution in
      populations.

PMID- 29025871
TI  - Audiograms of three subterranean rodent species (genus Fukomys) determined by
      auditory brainstem responses reveal extremely poor high-frequency hearing.
AB  - Life underground has shaped the auditory sense of subterranean mammals, shifting
      their hearing range to low frequencies. Mole-rats of the genus Fukomys have,
      however, been suggested to hear at frequencies up to 18.5 kHz, unusually high for
      a subterranean rodent. We present audiograms of three mole-rat species, Fukomys
      anselli, Fukomys micklemi and the giant mole-rat Fukomys mechowii, based on
      evoked auditory brainstem potentials. All species showed low sensitivity and
      restricted hearing ranges at 60 dB SPL extending from 125 Hz to 4 kHz (5 octaves)
      with most-sensitive hearing between 0.8 kHz and 1.4 kHz. The high-frequency cut
      offs are the lowest found in mammals to date. In contrast to predictions from
      middle ear morphology, F. mechowii did not show higher sensitivity than F.
      anselli in the low-frequency range. These data suggest that the hearing range of
      Fukomys mole-rats is highly restricted to low frequencies and similar to that of
      other subterranean mammals.

PMID- 29025872
TI  - Sirtuins regulate proteomic responses near thermal tolerance limits in the blue
      mussels Mytilus galloprovincialis and Mytilus trossulus.
AB  - The blue mussels Mytilus galloprovincialis and M. trossulus are competing species
      with biogeographical ranges set in part by environmental exposure to heat and
      hyposalinity. The underlying cellular mechanisms influencing interspecific
      differences in stress tolerance are unknown, but are believed to be under
      regulation by sirtuins, nicotinamide adenine dinucleotide (NAD+)-dependent
      deacylases that play a critical role in the cellular stress response. A
      comparison of the proteomic responses of M. galloprovincialis and M. trossulus to
      an acute heat shock in the presence and absence of the sirtuin inhibitor suramin
      (SIRT1, 2 and 5) showed that sirtuins affected molecular chaperones, oxidative
      stress proteins, metabolic enzymes, cytoskeletal and signaling proteins more in
      the heat-sensitive M. trossulus than in the heat-tolerant M. galloprovincialis
      Interactions between sirtuin inhibition and changes in the abundance of proteins
      of beta-oxidation and oxidative stress in M. trossulus suggest a greater role of
      sirtuins in shifting metabolism to reduce the production of reactive oxygen
      species near thermal limits. Furthermore, RNA-binding proteins initiating and
      inhibiting translation were affected by suramin in M. galloprovincialis and M.
      trossulus, respectively. Western blot analysis showed that the levels of
      mitochondrial sirtuin 5 (SIRT5) were generally three times higher and increased
      with acute heat stress in response to sirtuin inhibition in M. trossulus but not
      in M. galloprovincialis, suggesting a possible feedback response in the former
      species and a greater reliance on SIRT5 for its stress response. Our findings
      suggest that SIRT5 plays an important role in setting interspecific differences
      in stress tolerance in Mytilus by affecting the stress proteome.

PMID- 29025874
TI  - Effect of Pokemon GO on incidence of fatal traffic injuries: a population-based
      quasi-experimental study using the national traffic collisions database in Japan.
AB  - Pokemon GO (Niantic Labs, released on 22 July 2016 in Japan) is an augmented
      reality game that gained huge popularity worldwide. Despite concern about Pokemon
      GO-related traffic collisions, the effect of playing Pokemon GO on the incidence
      of traffic injuries remains unknown. We performed a population-based quasi
      experimental study using national data from the Institute for Traffic Accident
      Research and Data Analysis, Japan. The outcome was incidence of traffic injuries.
      Of 127 082 000 people in Japan, 886 fatal traffic injuries were observed between
      1 June and 31 August in 2016. Regression discontinuity analysis showed a non
      significant change in incidence of fatal traffic injuries after the Pokemon GO
      release (0.017 deaths per million, 95%CI -0.036 to 0.071). This finding was
      similar to that obtained from a difference-in-differences analysis. Effect of
      Pokemon GO on fatal traffic injuries may be negligible.

PMID- 29025873
TI  - Ectopic expression of Pax4 in pancreatic delta cells results in beta-like cell
      neogenesis.
AB  - The recent demonstration that pancreatic alpha cells can be continuously
      regenerated and converted into beta-like cells upon ectopic expression of Pax4
      opened new avenues of research in the endocrine cell differentiation and diabetes
      fields. To determine whether such plasticity was also shared by delta cells, we
      generated and characterized transgenic animals that express Pax4 specifically in
      somatostatin-expressing cells. We demonstrate that the ectopic expression of Pax4
      in delta cells is sufficient to induce their conversion into functional beta-like
      cells. Importantly, this conversion induces compensatory mechanisms involving the
      reactivation of endocrine developmental processes that result in dramatic beta
      like cell hyperplasia. Importantly, these beta-like cells are functional and can
      partly reverse the consequences of chemically induced diabetes.

PMID- 29025875
TI  - A small-molecule compound inhibits a collagen-specific molecular chaperone and
      could represent a potential remedy for fibrosis.
AB  - Fibrosis can disrupt tissue structure and integrity and impair organ function.
      Fibrosis is characterized by abnormal collagen accumulation in the extracellular
      matrix. Pharmacological inhibition of collagen secretion therefore represents a
      promising strategy for the management of fibrotic disorders, such as liver and
      lung fibrosis. Hsp47 is an endoplasmic reticulum (ER)-resident collagen-specific
      molecular chaperone essential for correct folding of procollagen in the ER.
      Genetic deletion of Hsp47 or inhibition of its interaction with procollagen
      interferes with procollagen triple helix production, which vastly reduces
      procollagen secretion from fibroblasts. Thus, Hsp47 could be a potential and
      promising target for the management of fibrosis. In this study, we screened small
      molecule compounds that inhibit the interaction of Hsp47 with collagen from
      chemical libraries using surface plasmon resonance (BIAcore), and we found a
      molecule AK778 and its cleavage product Col003 competitively inhibited the
      interaction and caused the inhibition of collagen secretion by destabilizing the
      collagen triple helix. Structural information obtained with NMR analysis revealed
      that Col003 competitively binds to the collagen-binding site on Hsp47. We propose
      that these structural insights could provide a basis for designing more effective
      therapeutic drugs for managing fibrosis.

PMID- 29025877
TI  - Low Incidence of End-Stage Renal Disease in Childhood-Onset Type 1 Diabetes
      Followed for Up to 42 Years.
AB  - OBJECTIVE: End-stage renal disease (ESRD) is one of the most severe complications
      in type 1 diabetes. We aimed to estimate the cumulative incidence of ESRD in
      individuals with childhood-onset type 1 diabetes followed for up to 42 years.
      RESEARCH DESIGN AND METHODS: Data were based on the nationwide, population-based
      Norwegian Childhood Diabetes Registry and included case patients with new-onset
      type 1 diabetes (age <15 years) who had received a diagnosis during the periods
      1973-1982 and 1989-2012. Follow-up took place until the development of ESRD,
      death, emigration, or 30 November 2015. We estimated the cumulative incidence of
      ESRD by linking to the Norwegian Renal Registry. RESULTS: Among the 7,871
      patients, representing 147,714 person-years of follow-up, ESRD developed in 103
      individuals (1.3%). The mean time from the diagnosis of diabetes to the
      development of ESRD was 25.9 years (range 12.7-39.1). The cumulative incidence of
      ESRD was 0.7% (95% CI 0.4-1.0) at 20 years' diabetes duration, 2.9% (2.3-3.7) at
      30 years' duration, and 5.3% (4.3-6.5) at 40 years' duration. The risk of the
      development of ESRD was lower in women than in men (hazard ratio [HR] 0.61; 95%
      CI 0.41-0.91) and higher in individuals in whom diabetes had been diagnosed at 10
      14 years of age compared with those in whom it was diagnosed before 10 years of
      age (HR 1.29; 1.06-1.56). We did not identify any significant difference in the
      risk of the development of ESRD between those in whom diabetes was diagnosed in
      1973-1982 and in 1989-2012 (HR 0.80; 0.45-1.45). CONCLUSIONS: We report a very
      low incidence of ESRD among patients with childhood-onset diabetes in Norway. The
      risk was lower in women compared with men and in individuals in whom diabetes was
      diagnosed at a younger age.

PMID- 29025876
TI  - Mevalonate 5-diphosphate mediates ATP binding to the mevalonate diphosphate
      decarboxylase from the bacterial pathogen Enterococcus faecalis.
AB  - The mevalonate pathway produces isopentenyl diphosphate (IPP), a building block
      for polyisoprenoid synthesis, and is a crucial pathway for growth of the human
      bacterial pathogen Enterococcus faecalis The final enzyme in this pathway,
      mevalonate diphosphate decarboxylase (MDD), acts on mevalonate diphosphate
      (MVAPP) to produce IPP while consuming ATP. This essential enzyme has been
      suggested as a therapeutic target for the treatment of drug-resistant bacterial
      infections. Here, we report functional and structural studies on the mevalonate
      diphosphate decarboxylase from E. faecalis (MDDEF). The MDDEF crystal structure
      in complex with ATP (MDDEF-ATP) revealed that the phosphate-binding loop (amino
      acids 97-105) is not involved in ATP binding and that the phosphate tail of ATP
      in this structure is in an outward-facing position pointing away from the active
      site. This suggested that binding of MDDEF to MVAPP is necessary to guide ATP
      into a catalytically favorable position. Enzymology experiments show that the
      MDDEF performs a sequential ordered bi-substrate reaction with MVAPP as the first
      substrate, consistent with the isothermal titration calorimetry (ITC)
      experiments. On the basis of ITC results, we propose that this initial
      prerequisite binding of MVAPP enhances ATP binding. In summary, our findings
      reveal a substrate-induced substrate-binding event that occurs during the MDDEF
      catalyzed reaction. The disengagement of the phosphate-binding loop concomitant
      with the alternative ATP-binding configuration may provide the structural basis
      for antimicrobial design against these pathogenic enterococci.

PMID- 29025878
TI  - Elevated Postoperative Endogenous GLP-1 Levels Mediate Effects of Roux-en-Y
      Gastric Bypass on Neural Responsivity to Food Cues.
AB  - OBJECTIVE: It has been suggested that weight reduction and improvements in
      satiety after Roux-en-Y gastric bypass (RYGB) are partly mediated via
      postoperative neuroendocrine changes. Glucagon-like peptide-1 (GLP-1) is a gut
      hormone secreted after food ingestion and is associated with appetite and weight
      reduction, mediated via effects on the central nervous system (CNS). Secretion of
      GLP-1 is greatly enhanced after RYGB. We hypothesized that postoperative elevated
      GLP-1 levels contribute to the improved satiety regulation after RYGB via effects
      on the CNS. RESEARCH DESIGN AND METHODS: Effects of the GLP-1 receptor antagonist
      exendin 9-39 (Ex9-39) and placebo were assessed in 10 women before and after
      RYGB. We used functional MRI to investigate CNS activation in response to visual
      food cues (pictures) and gustatory food cues (consumption of chocolate milk),
      comparing results with Ex9-39 versus placebo before and after RYGB. RESULTS:
      After RYGB, CNS activation was reduced in the rolandic operculum and caudate
      nucleus in response to viewing food pictures (P = 0.03) and in the insula in
      response to consumption of palatable food (P = 0.003). GLP-1 levels were
      significantly elevated postoperatively (P < 0.001). After RYGB, GLP-1 receptor
      blockade resulted in a larger increase in activation in the caudate nucleus in
      response to food pictures (P = 0.02) and in the insula in response to palatable
      food consumption (P = 0.002). CONCLUSIONS: We conclude that the effects of RYGB
      on CNS activation in response to visual and gustatory food cues may be mediated
      by central effects of GLP-1. Our findings provide further insights into the
      mechanisms underlying the weight-lowering effects of RYGB.

PMID- 29025880
TI  - Pharmacological treatment optimisation for stable COPD: an endless story?
      Proposals from the Societe de Pneumologie de Langue Francaise.

PMID- 29025879
TI  - TCF7L2 Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1
      Diabetes.
AB  - OBJECTIVE: The phenotypic diversity of type 1 diabetes suggests heterogeneous
      etiopathogenesis. We investigated the relationship of type 2 diabetes-associated
      transcription factor 7 like 2 (TCF7L2) single nucleotide polymorphisms (SNPs)
      with immunologic and metabolic characteristics at type 1 diabetes diagnosis.
      RESEARCH DESIGN AND METHODS: We studied TrialNet participants with newly
      diagnosed autoimmune type 1 diabetes with available TCF7L2 rs4506565 and
      rs7901695 SNP data (n = 810; median age 13.6 years; range 3.3-58.6). We modeled
      the influence of carrying a TCF7L2 variant (i.e., having 1 or 2 minor alleles) on
      the number of islet autoantibodies and oral glucose tolerance test (OGTT)
      stimulated C-peptide and glucose measures at diabetes diagnosis. All analyses
      were adjusted for known confounders. RESULTS: The rs4506565 variant was a
      significant independent factor of expressing a single autoantibody, instead of
      multiple autoantibodies, at diagnosis (odds ratio [OR] 1.66 [95% CI 1.07, 2.57],
      P = 0.024). Interaction analysis demonstrated that this association was only
      significant in participants >=12 years old (n = 504; OR 2.12 [1.29, 3.47], P =
      0.003) but not younger ones (n = 306, P = 0.73). The rs4506565 variant was
      independently associated with higher C-peptide area under the curve (AUC) (P =
      0.008) and lower mean glucose AUC (P = 0.0127). The results were similar for the
      rs7901695 SNP. CONCLUSIONS: In this cohort of individuals with new-onset type 1
      diabetes, type 2 diabetes-linked TCF7L2 variants were associated with single
      autoantibody (among those >=12 years old), higher C-peptide AUC, and lower
      glucose AUC levels during an OGTT. Thus, carriers of the TCF7L2 variant had a
      milder immunologic and metabolic phenotype at type 1 diabetes diagnosis, which
      could be partly driven by type 2 diabetes-like pathogenic mechanisms.

PMID- 29025881
TI  - High-dose isoniazid in the shorter-course multidrug-resistant tuberculosis
      regimen in the Republic of Moldova.

PMID- 29025882
TI  - Mucolytics for COPD: negotiating a slippery slope towards proof of efficacy.

PMID- 29025883
TI  - A katG 315 mutation alone should not lead to exclusion of isoniazid in treatment
      of multidrug-resistant tuberculosis.

PMID- 29025885
TI  - "Long-term outcomes of bronchial thermoplasty in subjects with severe asthma: a
      comparison of 3-year follow-up results from two prospective multicentre studies."
      Geoffrey Chupp, Michel Laviolette, Lauren Cohn, Charlene McEvoy, Sandeep Bansal,
      Adrian Shifren, Sumita Khatri, G. Mark Grubb, Edmund McMullen, Racho Strauven and
      Joel N. Kline. Eur Respir J 2017; 50: 1700017.

PMID- 29025884
TI  - Lack of evidence of isoniazid efficacy for the treatment of MDR/XDR-TB in the
      presence of the katG 315T mutation.

PMID- 29025886
TI  - Th17 cytokines: novel potential therapeutic targets for COPD pathogenesis and
      exacerbations.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of
      the airways caused mainly by cigarette smoke exposure. COPD progression is marked
      by exacerbations of the disease, often associated with infections. Recent data
      show the involvement in COPD pathophysiology of interleukin (IL)-17 and IL-22,
      two cytokines that are important in the control of lung inflammation and
      infection. During the initiation and progression of the disease, increased IL-17
      secretion causes neutrophil recruitment, leading to chronic inflammation, airways
      obstruction and emphysema. In the established phase of COPD, a defective IL-22
      response facilitates pathogen-associated infections and disease exacerbations.
      Altered production of these cytokines involves a complex network of immune cells
      and dysfunction of antigen-presenting cells. In this review, we describe current
      knowledge on the involvement of IL-17 and IL-22 in COPD pathophysiology at steady
      state and during exacerbations, and discuss implications for COPD management and
      future therapeutic approaches.

PMID- 29025887
TI  - BRAF and NRAS mutations in circulating Langerhans-like CD1a+ cells in a patient
      with pulmonary Langerhans' cell histiocytosis.

PMID- 29025890
TI  - Passive smoking in relation to lung cancer incidence and histologic types in
      Norwegian adults: the HUNT study.

PMID- 29025889
TI  - Characterisation of asthma subgroups associated with circulating YKL-40 levels.
AB  - The chitinase-like protein YKL-40 mediates airway inflammation and serum levels
      are associated with asthma severity. However, asthma phenotypes associated with
      YKL-40 levels have not been precisely defined.We conducted an unsupervised
      cluster analysis of asthma patients treated at the Yale Center for Asthma and
      Airways Disease (n=156) to identify subgroups according to YKL-40 level. The
      resulting YKL-40 clusters were cross-validated in cohorts from the Severe Asthma
      Research Programme (n=167) and the New York University/Bellevue Asthma Repository
      (n=341). A sputum transcriptome analysis revealed molecular pathways associated
      with YKL-40 subgroups.Four YKL-40 clusters (C1-C4) were identified. C3 and C4 had
      high serum YKL-40 levels compared with C1 and C2. C3 was associated with earlier
      onset and longer duration of disease, severe airflow obstruction, and near-fatal
      asthma exacerbations. C4 had the highest serum YKL-40 levels, adult onset and
      less airflow obstruction, but frequent exacerbations. An airway transcriptome
      analysis in C3 and C4 showed activation of non-type 2 inflammatory
      pathways.Elevated serum YKL-40 levels were associated with two distinct clinical
      asthma phenotypes: one with irreversible airway obstruction and another with
      severe exacerbations. The YKL-40 clusters are potentially useful for
      identification of individuals with severe or exacerbation-prone asthma.

PMID- 29025888
TI  - Effect of erdosteine on the rate and duration of COPD exacerbations: the RESTORE
      study.
AB  - Oxidative stress contributes to chronic obstructive pulmonary disease (COPD)
      exacerbations and antioxidants can decrease exacerbation rates, although we lack
      data about the effect of such drugs on exacerbation duration.The RESTORE
      (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD)
      study was a prospective randomised, double-blind, placebo-controlled study,
      enrolling patients aged 40-80 years with Global Initiative for Chronic
      Obstructive Lung Disease stage II/III. Patients received erdosteine 300 mg twice
      daily or placebo added to usual COPD therapy for 12 months. The primary outcome
      was the number of acute exacerbations during the study.In the pre-specified
      intention-to-treat population of 445 patients (74% male; mean age 64.8 years,
      forced expiratory volume in 1 s 51.8% predicted) erdosteine reduced the
      exacerbation rate by 19.4% (0.91 versus 1.13 exacerbations.patient-1.year-1 for
      erdosteine and placebo, respectively; p=0.01), due to an effect on mild events;
      the reduction in the rate of mild exacerbations was 57.1% (0.23 versus 0.54
      exacerbations.patient-1.year-1 for erdosteine and placebo, respectively;
      p=0.002). No significant difference was observed in the rate of moderate and
      severe exacerbations (0.68 versus 0.59 exacerbations.patient-1.year-1 for
      erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the
      comparison group. Erdosteine decreased the exacerbation duration irrespective of
      event severity by 24.6% (9.55 versus 12.63 days for erdosteine and placebo,
      respectively; p=0.023). Erdosteine significantly improved subject and physician
      subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the
      use of reliever medication (p<0.001), but did not affect the St George's
      Respiratory Questionnaire score or the time to first exacerbation.In patients
      with COPD, erdosteine can reduce both the rate and duration of exacerbations. The
      percentage of patients with adverse events was similar in both the placebo and
      erdosteine treatment groups.

PMID- 29025892
TI  - Evaluation of tuberculosis screening of immigrants in the Netherlands.

PMID- 29025891
TI  - Impact and associations of eosinophilic inflammation in COPD: analysis of the
      AERIS cohort.
AB  - Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD)
      predicts response to treatment, especially corticosteroids. We studied the nature
      of eosinophilic inflammation in COPD prospectively to examine the stability of
      this phenotype and its dynamics across exacerbations, and its associations with
      clinical phenotype, exacerbations and infection.127 patients aged 40-85 years
      with moderate to very severe COPD underwent repeated blood and sputum sampling at
      stable visits and within 72 h of exacerbation for 1 year.Blood eosinophils >=2%
      was prevalent at baseline, and predicted both predominantly raised stable-state
      eosinophils across the year (area under the curve 0.841, 95% CI 0.755-0.928) and
      increased risk of eosinophilic inflammation at exacerbation (OR 9.16; p<0.001).
      Eosinophils >=2% at exacerbation and eosinophil predominance at stable visits
      were associated with a lower risk of bacterial presence at exacerbation (OR 0.49;
      p=0.049 and OR 0.25; p=0.065, respectively). Bacterial infection at exacerbation
      was highly seasonal (winter versus summer OR 4.74; p=0.011) in predominantly
      eosinophilic patients.Eosinophilic inflammation is a common and stable phenotype
      in COPD. Blood eosinophil counts in the stable state can predict the nature of
      inflammation at future exacerbations, which when combined with an understanding
      of seasonal variation provides the basis for the development of new treatment
      paradigms for this important condition.

PMID- 29025893
TI  - Disease-specific biases in alternative splicing and tissue-specific dysregulation
      revealed by multitissue profiling of lymphocyte gene expression in type 1
      diabetes.
AB  - Genome-wide association studies (GWAS) have identified multiple, shared allelic
      associations with many autoimmune diseases. However, the pathogenic contributions
      of variants residing in risk loci remain unresolved. The location of the majority
      of shared disease-associated variants in noncoding regions suggests they
      contribute to risk of autoimmunity through effects on gene expression in the
      immune system. In the current study, we test this hypothesis by applying RNA
      sequencing to CD4+, CD8+, and CD19+ lymphocyte populations isolated from 81
      subjects with type 1 diabetes (T1D). We characterize and compare the expression
      patterns across these cell types for three gene sets: all genes, the set of genes
      implicated in autoimmune disease risk by GWAS, and the subset of these genes
      specifically implicated in T1D. We performed RNA sequencing and aligned the reads
      to both the human reference genome and a catalog of all possible splicing events
      developed from the genome, thereby providing a comprehensive evaluation of the
      roles of gene expression and alternative splicing (AS) in autoimmunity.
      Autoimmune candidate genes displayed greater expression specificity in the three
      lymphocyte populations relative to other genes, with significantly increased
      levels of splicing events, particularly those predicted to have substantial
      effects on protein isoform structure and function (e.g., intron retention, exon
      skipping). The majority of single-nucleotide polymorphisms within T1D-associated
      loci were also associated with one or more cis-expression quantitative trait loci
      (cis-eQTLs) and/or splicing eQTLs. Our findings highlight a substantial, and
      previously underrecognized, role for AS in the pathogenesis of autoimmune
      disorders and particularly for T1D.

PMID- 29025895
TI  - Accounting for GC-content bias reduces systematic errors and batch effects in
      ChIP-seq data.
AB  - The main application of ChIP-seq technology is the detection of genomic regions
      that bind to a protein of interest. A large part of functional genomics' public
      catalogs is based on ChIP-seq data. These catalogs rely on peak calling
      algorithms that infer protein-binding sites by detecting genomic regions
      associated with more mapped reads (coverage) than expected by chance, as a result
      of the experimental protocol's lack of perfect specificity. We find that GC
      content bias accounts for substantial variability in the observed coverage for
      ChIP-seq experiments and that this variability leads to false-positive peak
      calls. More concerning is that the GC effect varies across experiments, with the
      effect strong enough to result in a substantial number of peaks called
      differently when different laboratories perform experiments on the same cell
      line. However, accounting for GC content bias in ChIP-seq is challenging because
      the binding sites of interest tend to be more common in high GC-content regions,
      which confounds real biological signals with unwanted variability. To account for
      this challenge, we introduce a statistical approach that accounts for GC effects
      on both nonspecific noise and signal induced by the binding site. The method can
      be used to account for this bias in binding quantification as well to improve
      existing peak calling algorithms. We use this approach to show a reduction in
      false-positive peaks as well as improved consistency across laboratories.

PMID- 29025894
TI  - Nascent RNA sequencing reveals a dynamic global transcriptional response at genes
      and enhancers to the natural medicinal compound celastrol.
AB  - Most studies of responses to transcriptional stimuli measure changes in cellular
      mRNA concentrations. By sequencing nascent RNA instead, it is possible to detect
      changes in transcription in minutes rather than hours and thereby distinguish
      primary from secondary responses to regulatory signals. Here, we describe the use
      of PRO-seq to characterize the immediate transcriptional response in human cells
      to celastrol, a compound derived from traditional Chinese medicine that has
      potent anti-inflammatory, tumor-inhibitory, and obesity-controlling effects.
      Celastrol is known to elicit a cellular stress response resembling the response
      to heat shock, but the transcriptional basis of this response remains unclear.
      Our analysis of PRO-seq data for K562 cells reveals dramatic transcriptional
      effects soon after celastrol treatment at a broad collection of both coding and
      noncoding transcription units. This transcriptional response occurred in two
      major waves, one within 10 min, and a second 40-60 min after treatment.
      Transcriptional activity was generally repressed by celastrol, but one distinct
      group of genes, enriched for roles in the heat shock response, displayed strong
      activation. Using a regression approach, we identified key transcription factors
      that appear to drive these transcriptional responses, including members of the
      E2F and RFX families. We also found sequence-based evidence that particular
      transcription factors drive the activation of enhancers. We observed increased
      polymerase pausing at both genes and enhancers, suggesting that pause release may
      be widely inhibited during the celastrol response. Our study demonstrates that a
      careful analysis of PRO-seq time-course data can disentangle key aspects of a
      complex transcriptional response, and it provides new insights into the activity
      of a powerful pharmacological agent.

PMID- 29025896
TI  - High-throughput single-molecule telomere characterization.
AB  - We have developed a novel method that enables global subtelomere and haplotype
      resolved analysis of telomere lengths at the single-molecule level. An in vitro
      CRISPR/Cas9 RNA-directed nickase system directs the specific labeling of human
      (TTAGGG)n DNA tracts in genomes that have also been barcoded using a separate
      nickase enzyme that recognizes a 7-bp motif genome-wide. High-throughput imaging
      and analysis of large DNA single molecules from genomes labeled in this fashion
      using a nanochannel array system permits mapping through subtelomere repeat
      element (SRE) regions to unique chromosomal DNA while simultaneously measuring
      the (TTAGGG)n tract length at the end of each large telomere-terminal DNA
      segment. The methodology also permits subtelomere and haplotype-resolved analyses
      of SRE organization and variation, providing a window into the population
      dynamics and potential functions of these complex and structurally variant
      telomere-adjacent DNA regions. At its current stage of development, the assay can
      be used to identify and characterize telomere length distributions of 30-35
      discrete telomeres simultaneously and accurately. The assay's utility is
      demonstrated using early versus late passage and senescent human diploid
      fibroblasts, documenting the anticipated telomere attrition on a global telomere
      by-telomere basis as well as identifying subtelomere-specific biases for
      critically short telomeres. Similarly, we present the first global single
      telomere-resolved analyses of two cancer cell lines.

PMID- 29025898
TI  - Aging is associated with increased propensity for central apnea during NREM
      sleep.
AB  - The reason for increased sleep-disordered breathing with predominance of central
      apneas in the elderly is unknown. We hypothesized that the propensity to central
      apneas is increased in older adults, manifested by a reduced carbon-dioxide (CO2)
      reserve in older compared with young adults during non-rapid eye movement sleep.
      Ten elderly and 15 young healthy adults underwent multiple brief trials of nasal
      noninvasive positive pressure ventilation during stable NREM sleep. Cessation of
      mechanical ventilation (MV) resulted in hypocapnic central apnea or hypopnea. The
      CO2 reserve was defined as the difference in end-tidal CO2 ([Formula: see text])
      between eupnea and the apneic threshold, where the apneic threshold was [Formula:
      see text] that demarcated the central apnea closest to the eupneic [Formula: see
      text]. For each MV trial, the hypocapnic ventilatory response (controller gain)
      was measured as the change in minute ventilation (Ve) during the MV trial for a
      corresponding change in [Formula: see text]. The eupneic [Formula: see text] was
      significantly lower in elderly vs. young adults. Compared with young adults, the
      elderly had a significantly reduced CO2 reserve (-2.6 +/- 0.4 vs. -4.1 +/- 0.4
      mmHg, P = 0.01) and a higher controller gain (2.3 +/- 0.2 vs. 1.4 +/- 0.2 l.min
      1.mmHg-1, P = 0.007), indicating increased chemoresponsiveness in the elderly.
      Thus elderly adults are more prone to hypocapnic central apneas owing to
      increased hypocapnic chemoresponsiveness during NREM sleep. NEW & NOTEWORTHY The
      study describes an original finding where healthy older adults compared with
      healthy young adults demonstrated increased breathing instability during non
      rapid eye movement sleep, as suggested by a smaller carbon dioxide reserve and a
      higher controller gain. The findings may explain the increased propensity for
      central apneas in elderly adults during sleep and potentially guide the
      development of pathophysiology-defined personalized therapies for sleep apnea in
      the elderly.

PMID- 29025899
TI  - A novel single-beat approach to assess right ventricular systolic function.
AB  - Clinical assessment of right ventricular (RV) contractility in diseases such as
      pulmonary arterial hypertension (PAH) has been hindered by the lack of a robust
      methodology. Here, a novel, clinically viable, single-beat method was developed
      to assess end-systolic elastance (Ees), a measure of right ventricular (RV)
      contractility. We hypothesized that this novel approach reduces uncertainty and
      interobserver variability in the estimation of the maximum isovolumic pressure
      (Piso), the key step in single-beat methods. The new method was designed to
      include a larger portion of the RV pressure data and minimize subjective
      adjustments by the operator. Data were obtained from right heart catheterization
      of PAH patients in a multicenter prospective study ( data set 1) and a single
      center retrospective study ( data set 2). To obtain Piso, three independent
      observers used an established single-beat method (based on the first derivative
      of the pressure waveform) and the novel method (based on the second derivative).
      Interobserver variability analysis included paired t-test, one-way ANOVA,
      interclass correlation (ICC) analysis, and a modified Bland-Altman analysis. The
      Piso values obtained from the two methods were linearly correlated for both data
      set 1 ( R2 = 0.74) and data set 2 ( R2 = 0.91). Compared with the established
      method, the novel method resulted in smaller interobserver variability ( P <
      0.001), nonsignificant differences between observers, and a narrower confidence
      interval. By reducing uncertainty and interobserved variability, this novel
      approach may pave the way for more effective clinical management of PAH. NEW &
      NOTEWORTHY A novel methodology to assess right ventricular contractility from
      clinical data is demonstrated. This approach significantly reduces interobserver
      variability in the analysis of ventricular pressure data, as demonstrated in a
      relatively large population of subjects with pulmonary hypertension. This study
      may enable more accurate clinical monitoring of systolic function in subjects
      with pulmonary hypertension.

PMID- 29025900
TI  - Multiple coupled resonances in the human vascular tree: refining the Westerhof
      model of the arterial system.
AB  - The human arterial vascular tree can be described by multicompartment models
      using electrical components. First introduced in the 1960s by Noordergraaf and
      Westerhof, these hardware-based approaches required several simplifications. We
      were able to remove the restrictions using modern software simulation tools and
      improve overall model quality considerably. Whereas the original Westerhof model
      consisted of 121 Windkessel elements, the refined model has 711 elements and
      gives realistic pulse waveforms of the aorta and brachial and radial arteries
      with realistic blood pressures. Moreover, novel insights concerning the formation
      of the physiological aortic-to-radial transfer function were gained. Its being
      potentially due to the coupling of many small resonant elements gives new impetus
      to the discussion of arterial pressure wave reflection. The individualized
      transfer function derived from our improved model incorporates distinct patient
      characteristics and can potentially be used for estimation of central blood
      pressure values. NEW & NOTEWORTHY We were able to find an individualized transfer
      function giving realistic pulse waveforms and blood pressures using a
      multicompartment model of the arterial system. Based on the hardware-built
      Westerhof approach, several simplifications initially introduced in the 1960s
      could be reversed using software simulation. Overall model quality was improved
      considerably, and multiple coupled resonances were identified as potential
      explanation for the formation of the aortic-to-radial transfer function, giving
      new impetus to the discussion of arterial pressure wave reflection.

PMID- 29025897
TI  - A Drosophila model of insulin resistance associated with the human TRIB3 Q/R
      polymorphism.
AB  - Members of the Tribbles family of proteins are conserved pseudokinases with
      diverse roles in cell growth and proliferation. Both Drosophila Tribbles (Trbl)
      and vertebrate Trib3 proteins bind to the kinase Akt (Akt1) to block its
      phosphorylation activation and reduce downstream insulin-stimulated anabolism. A
      single nucleotide polymorphism (SNP) variant in human TRIB3, which results in a
      glutamine (Q) to arginine (R) missense mutation in a conserved motif at position
      84, confers stronger Akt binding, resulting in reduced Akt phosphorylation, and
      is associated with a predisposition to Type 2 diabetes, cardiovascular disease,
      diabetic nephropathy, chronic kidney disease and leukemogenesis. Here, we used a
      Drosophila model to understand the importance of the conserved R residue in
      several Trbl functions. In the fly fat body, misexpression of a site-directed Q
      mutation at position R141 resulted in weakened binding to Drosophila Akt (dAkt),
      leading to increased levels of phospho-dAkt, increased cell and tissue size, and
      increases in the levels of stored glycogen and triglycerides. Consistent with the
      functional conservation of this arginine in modulating Akt activity, mouse Trib3
      R84 misexpressed in the fly fat body blocked dAkt phosphorylation with a strength
      similar to wild-type Trbl. Limited mutational analysis shows that the R141 site
      dictates the strength of Akt binding but does not affect other Trbl-dependent
      developmental processes, suggesting a specificity that could serve as a drug
      target for metabolic diseases.

PMID- 29025902
TI  - Relative contributions of systemic hemodynamic variables to cerebral
      autoregulation during orthostatic stress.
AB  - Postural changes impair the ability of the cerebrovasculature to buffer against
      dynamic pressure fluctuations, but the mechanisms underlying this impairment have
      not been elucidated. We hypothesized that autoregulatory impairment may reflect
      the impact of static central volume shifts on hemodynamic factors other than
      arterial pressure (AP). In 14 young volunteers, we assessed the relation of
      fluctuations in cerebral blood flow (CBF) to those in AP, cardiac output, and
      CO2, during oscillatory lower body pressure (LBP) (+/-20 mmHg at 0.01 and 0.06
      Hz) at three static levels (-20, 0, and +20 mmHg). Static and dynamic changes in
      AP, cardiac output, and CO2 explained over 70% of the variation in CBF
      fluctuations. However, their contributions were different across frequencies and
      levels: dynamic AP changes explained a substantial proportion of the variation in
      faster CBF fluctuations (partial R2 = 0.75, standardized beta = 0.83, P < 0.01),
      whereas those in CO2 explained the largest portion of the variation in slow
      fluctuations (partial R2 = 0.43, beta = 0.51, P < 0.01). There was, however, a
      major contribution of slow dynamic AP changes during negative (beta = 0.43) but
      not neutral (beta = 0.05) or positive (beta = -0.07) LBP. This highlights the
      differences in contributions of systemic variables to dynamic and static
      autoregulation and has important implications for understanding orthostatic
      intolerance. NEW & NOTEWORTHY While fluctuations in blood pressure drive faster
      fluctuations in cerebral blood flow, overall level of CO2 and the magnitude of
      its fluctuations, along with cardiac output, determine the magnitude of slow
      ones. The effect of slow blood pressure fluctuations on cerebrovascular responses
      becomes apparent only during pronounced central volume shifts (such as when
      standing). This underlines distinct but interacting contributions of static and
      dynamic changes in systemic hemodynamic variables to the cerebrovascular
      regulation.

PMID- 29025903
TI  - Translation in Progress: Hypoxia 2017.

PMID- 29025901
TI  - Effects of age and exercise training on coronary microvascular smooth muscle
      phenotype and function.
AB  - Coronary microvascular function and blood flow responses during acute exercise
      are impaired in the aged heart but can be restored by exercise training. Coronary
      microvascular resistance is directly dependent on vascular smooth muscle function
      in coronary resistance arterioles; therefore, we hypothesized that age impairs
      contractile function and alters the phenotype of vascular smooth muscle in
      coronary arterioles. We further hypothesized that exercise training restores
      contractile function and reverses age-induced phenotypic alterations of
      arteriolar smooth muscle. Young and old Fischer 344 rats underwent 10 wk of
      treadmill exercise training or remained sedentary. At the end of training or cage
      confinement, contractile responses, vascular smooth muscle proliferation, and
      expression of contractile proteins were assessed in isolated coronary arterioles.
      Both receptor- and non-receptor-mediated contractile function were impaired in
      coronary arterioles from aged rats. Vascular smooth muscle shifted from a
      differentiated, contractile phenotype to a secretory phenotype with associated
      proliferation of smooth muscle in the arteriolar wall. Expression of smooth
      muscle myosin heavy chain 1 (SM1) was decreased in arterioles from aged rats,
      whereas expression of phospho-histone H3 and of the synthetic protein ribosomal
      protein S6 (rpS6) were increased. Exercise training improved contractile
      responses, reduced smooth muscle proliferation and expression of rpS6, and
      increased expression of SM1 in arterioles from old rats. Thus age-induced
      contractile dysfunction of coronary arterioles and emergence of a secretory
      smooth muscle phenotype may contribute to impaired coronary blood flow responses,
      but arteriolar contractile responsiveness and a younger smooth muscle phenotype
      can be restored with late-life exercise training. NEW & NOTEWORTHY Aging impairs
      contractile function of coronary arterioles and induces a shift of the vascular
      smooth muscle toward a proliferative, noncontractile phenotype. Late-life
      exercise training reverses contractile dysfunction of coronary arterioles and
      restores a young phenotype to the vascular smooth muscle.

PMID- 29025904
TI  - Imaging in metabolic research: challenges and opportunities.

PMID- 29025905
TI  - Clinical severity in adult warm autoimmune hemolytic anemia and its relationship
      to antibody specificity.

PMID- 29025906
TI  - Comparative profiling of HLA-DR and HLA-DQ associated factor VIII peptides
      presented by monocyte-derived dendritic cells.
AB  - The development of anti-factor VIII antibodies is a major complication of the
      treatment of patients with hemophilia A. Generation of high affinity anti-factor
      VIII antibodies is dependent on help provided by CD4+ T cells that recognize
      factor VIII-derived peptides presented on class II major histocompatibility
      complex on the surface of antigen-presenting cells. In order to identify the
      immune-dominant epitopes that can be presented to CD4+ T cells, we previously
      developed a mass spectrometry-based method to identify factor VIII-derived
      peptides that are presented on human leukocyte antigen (HLA)-DR. In the present
      work, we compared the repertoire of FVIII-derived peptide presented on HLA-DR and
      HLA-DQ. Monocyte-derived dendritic cells from nine HLA-typed healthy donors were
      pulsed with recombinant factor VIII. HLA-DR and HLA-DQ molecules were purified
      using monoclonal antibodies. Our data show that HLA-DQ and HLA-DR present a
      similar repertoire of factor VIII-derived peptides. However, the number of
      peptides associated with HLA-DQ was lower than that with HLA-DR. We also
      identified a peptide, within the acidic a3 domains of factor VIII, which is
      presented with higher frequency on HLA-DQ. Interestingly, this peptide was found
      to have a higher predicted affinity for HLA-DQ than for HLA-DR. Taken together,
      our data suggest that HLA-DQ participates in the presentation of factor VIII
      peptides, thereby contributing to the development of inhibitory antibodies in a
      proportion of patients with severe hemophilia A.

PMID- 29025908
TI  - A germ-line deletion of APOBEC3B does not contribute to subtype-specific
      childhood acute lymphoblastic leukemia etiology.

PMID- 29025909
TI  - Histone deacetylase inhibitors downregulate CCR4 expression and decrease
      mogamulizumab efficacy in CCR4-positive mature T-cell lymphomas.
AB  - Histone deacetylase inhibitors are promising agents for various T-cell lymphomas,
      including cutaneous T-cell lymphoma, peripheral T-cell lymphoma, and adult T-cell
      lymphoma/leukemia. CCR4 is an important therapeutic target molecule because
      mogamulizumab, an anti-CCR4 antibody, has shown promising efficacy against
      various T-cell lymphomas. In this study, we examined the in vitro synergistic
      effects of mogamulizumab and histone deacetylase inhibitors against various T
      cell lymphomas. First, we examined the expression of CCR4 mRNA and surface CCR4
      in various T-cell lymphoma cell lines and found that it was downregulated upon
      treatment with vorinostat, a pan-histone deacetylase inhibitor. Next, we used
      isoform-specific histone deacetylase inhibitors and short-interfering RNA to
      determine the histone deacetylase isoform involved in the regulation of CCR4, and
      demonstrated that romidepsin, a class I selective histone deacetylase inhibitor,
      reduced CCR4 most efficiently. Moreover, among class I histone deacetylases,
      histone deacetylase 2 knockdown led to a reduction of CCR4 in lymphoma cells,
      suggesting that CCR4 expression is mainly regulated by histone deacetylase 2.
      When we examined the CCR4 expression in skin samples from primary cutaneous T
      cell lymphoma, obtained from the same patients before and after vorinostat
      treatment, we found that CCR4 expression was greatly reduced after treatment.
      Finally, when we conducted an antibody-dependent cell-mediated cytotoxicity assay
      with mogamulizumab by using various lymphoma cells, we found that the efficacy of
      mogamulizumab was significantly reduced by pretreatment with vorinostat.
      Altogether, our results suggest that the primary use of histone deacetylase
      inhibitors before treatment with mogamulizumab might not be suitable to obtain
      synergistic effects. Moreover, these results have potential implications for
      optimal therapeutic sequences in various CCR4-positive T-cell lymphomas.

PMID- 29025907
TI  - Depletion of SIRT6 enzymatic activity increases acute myeloid leukemia cells'
      vulnerability to DNA-damaging agents.
AB  - Genomic instability plays a pathological role in various malignancies, including
      acute myeloid leukemia (AML), and thus represents a potential therapeutic target.
      Recent studies demonstrate that SIRT6, a NAD+-dependent nuclear deacetylase,
      functions as genome-guardian by preserving DNA integrity in different tumor
      cells. Here, we demonstrate that also CD34+ blasts from AML patients show ongoing
      DNA damage and SIRT6 overexpression. Indeed, we identified a poor-prognostic
      subset of patients, with widespread instability, which relies on SIRT6 to
      compensate for DNA-replication stress. As a result, SIRT6 depletion compromises
      the ability of leukemia cells to repair DNA double-strand breaks that, in turn,
      increases their sensitivity to daunorubicin and Ara-C, both in vitro and in vivo
      In contrast, low SIRT6 levels observed in normal CD34+ hematopoietic progenitors
      explain their weaker sensitivity to genotoxic stress. Intriguingly, we have
      identified DNA-PKcs and CtIP deacetylation as crucial for SIRT6-mediated DNA
      repair. Together, our data suggest that inactivation of SIRT6 in leukemia cells
      leads to disruption of DNA-repair mechanisms, genomic instability and aggressive
      AML. This synthetic lethal approach, enhancing DNA damage while concomitantly
      blocking repair responses, provides the rationale for the clinical evaluation of
      SIRT6 modulators in the treatment of leukemia.

PMID- 29025911
TI  - Treat or palliate: outcomes of very elderly myeloma patients.

PMID- 29025910
TI  - Protein arginine methyltransferase 6 controls erythroid gene expression and
      differentiation of human CD34+ progenitor cells.
AB  - Hematopoietic differentiation is driven by transcription factors, which
      orchestrate a finely tuned transcriptional network. At bipotential branching
      points lineage decisions are made, where key transcription factors initiate cell
      type-specific gene expression programs. These programs are stabilized by the
      epigenetic activity of recruited chromatin-modifying cofactors. An example is the
      association of the transcription factor RUNX1 with protein arginine
      methyltransferase 6 (PRMT6) at the megakaryocytic/erythroid bifurcation. However,
      little is known about the specific influence of PRMT6 on this important branching
      point. Here, we show that PRMT6 inhibits erythroid gene expression during
      megakaryopoiesis of primary human CD34+ progenitor cells. PRMT6 is recruited to
      erythroid genes, such as glycophorin A Consequently, a repressive histone
      modification pattern with high H3R2me2a and low H3K4me3 is established.
      Importantly, inhibition of PRMT6 by shRNA or small molecule inhibitors leads to
      upregulation of erythroid genes and promotes erythropoiesis. Our data reveal that
      PRMT6 plays a role in the control of erythroid/megakaryocytic differentiation and
      open up the possibility that manipulation of PRMT6 activity could facilitate
      enhanced erythropoiesis for therapeutic use.

PMID- 29025912
TI  - Variable outcome and methylation status according to CEBPA mutant type in double
      mutated acute myeloid leukemia patients and the possible implications for
      treatment.
AB  - Although CEBPA double-mutated (CEBPADM) acute myeloid leukemia is considered to
      be a favorable-risk disease, relapse remains a major cause of treatment failure.
      Most CEBPADM patients have a classic biallelic mutant combination with an N
      terminal mutation leading to production of p30 protein plus a C-terminal loss-of
      function in-frame indel mutation (CEBPAClassic-DM), but approximately one-third
      of cases have one or more non-classic mutations, with diverse combinations
      reported, and there is little information on the consequences of such mutants. We
      evaluated outcome in a cohort of 104 CEBPADM patients, 79 CEBPAClassic-DM and 25
      with non-classic mutants, and found that the latter may have poorer survival (5
      year overall survival 64% vs. 46%; P=0.05), particularly post relapse (41% vs.
      0%; P=0.02). However, for this analysis, all non-classic cases were grouped
      together, irrespective of mutant combination. As CEBPADM cases have been reported
      to be hypermethylated, we used methylation profiling to assess whether this could
      segregate the different mutants. We developed a CEBPAClassic-DM methylation
      signature from a preliminary cohort of 10 CEBPADM (including 8 CEBPAClassic-DM)
      and 30 CEBPA wild-type (CEBPAWT) samples, and independently validated the
      signature in 17 CEBPAClassic-DM cases. Assessment of the signature in 16 CEBPADM
      cases with different non-classic mutant combinations showed that only 31% had a
      methylation profile equivalent to CEBPAClassic-DM whereas for 69% the profile was
      either intermediate between CEBPAClassic-DM and CEBPAWT or equivalent to CEBPAWT
      These results suggest that CEBPADM cases with non-classic mutants may be
      functionally different from those with CEBPAClassic-DM mutants, and should not
      automatically be included in the same prognostic group. (AML12 is registered
      under ISRCTN17833622 and AML15 under ISRCTN17161961).

PMID- 29025914
TI  - Dendritic Cytoskeletal Architecture Is Modulated by Combinatorial Transcriptional
      Regulation in Drosophila melanogaster.
AB  - Transcription factors (TFs) have emerged as essential cell autonomous mediators
      of subtype specific dendritogenesis; however, the downstream effectors of these
      TFs remain largely unknown, as are the cellular events that TFs control to direct
      morphological change. As dendritic morphology is largely dictated by the
      organization of the actin and microtubule (MT) cytoskeletons, elucidating TF
      mediated cytoskeletal regulatory programs is key to understanding molecular
      control of diverse dendritic morphologies. Previous studies in Drosophila
      melanogaster have demonstrated that the conserved TFs Cut and Knot exert
      combinatorial control over aspects of dendritic cytoskeleton development,
      promoting actin and MT-based arbor morphology, respectively. To investigate
      transcriptional targets of Cut and/or Knot regulation, we conducted systematic
      neurogenomic studies, coupled with in vivo genetic screens utilizing multi-fluor
      cytoskeletal and membrane marker reporters. These analyses identified a host of
      putative Cut and/or Knot effector molecules, and a subset of these putative TF
      targets converge on modulating dendritic cytoskeletal architecture, which are
      grouped into three major phenotypic categories, based upon neuromorphometric
      analyses: complexity enhancer, complexity shifter, and complexity suppressor.
      Complexity enhancer genes normally function to promote higher order dendritic
      growth and branching with variable effects on MT stabilization and F-actin
      organization, whereas complexity shifter and complexity suppressor genes normally
      function in regulating proximal-distal branching distribution or in restricting
      higher order branching complexity, respectively, with spatially restricted
      impacts on the dendritic cytoskeleton. Collectively, we implicate novel genes and
      cellular programs by which TFs distinctly and combinatorially govern
      dendritogenesis via cytoskeletal modulation.

PMID- 29025915
TI  - RL-SKAT: An Exact and Efficient Score Test for Heritability and Set Tests.
AB  - Testing for the existence of variance components in linear mixed models is a
      fundamental task in many applicative fields. In statistical genetics, the score
      test has recently become instrumental in the task of testing an association
      between a set of genetic markers and a phenotype. With few markers, this amounts
      to set-based variance component tests, which attempt to increase power in
      association studies by aggregating weak individual effects. When the entire
      genome is considered, it allows testing for the heritability of a phenotype,
      defined as the proportion of phenotypic variance explained by genetics. In the
      popular score-based Sequence Kernel Association Test (SKAT) method, the assumed
      distribution of the score test statistic is uncalibrated in small samples, with a
      correction being computationally expensive. This may cause severe inflation or
      deflation of P-values, even when the null hypothesis is true. Here, we
      characterize the conditions under which this discrepancy holds, and show it may
      occur also in large real datasets, such as a dataset from the Wellcome Trust Case
      Control Consortium 2 (n = 13,950) study, and, in particular, when the individuals
      in the sample are unrelated. In these cases, the SKAT approximation tends to be
      highly overconservative and therefore underpowered. To address this limitation,
      we suggest an efficient method to calculate exact P-values for the score test in
      the case of a single variance component and a continuous response vector, which
      can speed up the analysis by orders of magnitude. Our results enable fast and
      accurate application of the score test in heritability and in set-based
      association tests. Our method is available in http://github.com/cozygene/RL-SKAT.

PMID- 29025913
TI  - Analyses of the FranceCoag cohort support differences in immunogenicity among one
      plasma-derived and two recombinant factor VIII brands in boys with severe
      hemophilia A.
AB  - Around one third of boys with severe hemophilia A develop inhibitors
      (neutralizing antibodies) against their therapeutic factor VIII product. This
      adverse effect may result in more life-threatening bleeding, disability, impaired
      quality of life, and costly care. We compared the incidence of inhibitors in boys
      treated with the three factor VIII products most used in France: one plasma
      derived (Factane) and two recombinant products (Advate and Kogenate Bayer). A
      previously untreated cohort of patients was created in 1994 to investigate risk
      factors for inhibitor development. We selected boys with severe hemophilia A
      (factor VIII <1 IU/dL) first treated with one of the three factor VIII products
      studied. Details of product infusions, inhibitor assays and main fixed and time
      varying inhibitor risk factors were recorded for the first 75 exposure days.
      Three outcomes (all inhibitors, high-titer inhibitors and subsequently treated
      inhibitors) were analyzed by univariate and multivariate Cox models. We studied
      395 boys first treated between 2001 and 2016 (131, 137, and 127 with Factane,
      Advate, and Kogenate Bayer, respectively). Clinically significant inhibitors were
      diagnosed in 121 patients (70 high-titer). The incidence of high-titer inhibitors
      was significantly associated with the factor VIII product received (P=0.005): the
      cumulative incidence at 75 exposure days was 12.7% (95% CI: 7.7-20.6) with
      Factane, 20.4% (95% CI: 14.0-29.1) with Advate, and 31.6% (95% CI: 23.5-41.7)
      with Kogenate Bayer. The low inhibitor incidence observed with Factane is
      concordant with recent findings from the SIPPET randomized trial. These
      consistent results from observational and experimental studies should lead to
      improved care for previously untreated patients and cost savings for healthcare
      systems worldwide.

PMID- 29025918
TI  - Contemporary endovascular and open aneurysm treatment in the era of flow
      diversion.
AB  - Clinical outcomes have improved considerably over the last decade for patients
      with ruptured and unruptured aneurysms. Modern endovascular techniques, such as
      flow diversion, are associated with high aneurysm occlusion rates and have become
      a popular treatment modality for many types of aneurysms. However, the safety and
      effectiveness of flow diversion has not yet been established in trials comparing
      it with traditional aneurysm treatments. Moreover, there are some types of
      aneurysms that may not be appropriate for endovascular coiling, such as wide
      necked aneurysms located at branch points of major vessels, large saccular
      aneurysms with multiple efferent arteries, dolichoectatic aneurysms, large
      aneurysms with mass effect, when there are technical complications with
      endovascular treatment, when patients cannot tolerate or have contraindications
      to antiplatelet therapy or in the setting of a subarachnoid haemorrhage. For
      these cases, open cerebrovascular surgery remains important. This review provides
      a discussion on the current trends and evidence for both flow diversion and open
      cerebrovascular surgery for complex aneurysms that may not be suitable for
      coiling. We emphasise a continued important role for surgical treatment in
      certain situations.

PMID- 29025916
TI  - A Predictive Model for Time-to-Flowering in the Common Bean Based on QTL and
      Environmental Variables.
AB  - The common bean is a tropical facultative short-day legume that is now grown in
      tropical and temperate zones. This observation underscores how domestication and
      modern breeding can change the adaptive phenology of a species. A key adaptive
      trait is the optimal timing of the transition from the vegetative to the
      reproductive stage. This trait is responsive to genetically controlled signal
      transduction pathways and local climatic cues. A comprehensive characterization
      of this trait can be started by assessing the quantitative contribution of the
      genetic and environmental factors, and their interactions. This study aimed to
      locate significant QTL (G) and environmental (E) factors controlling time-to
      flower in the common bean, and to identify and measure G * E interactions.
      Phenotypic data were collected from a biparental [Andean * Mesoamerican]
      recombinant inbred population (F11:14, 188 genotypes) grown at five
      environmentally distinct sites. QTL analysis using a dense linkage map revealed
      12 QTL, five of which showed significant interactions with the environment.
      Dissection of G * E interactions using a linear mixed-effect model revealed that
      temperature, solar radiation, and photoperiod play major roles in controlling
      common bean flowering time directly, and indirectly by modifying the effect of
      certain QTL. The model predicts flowering time across five sites with an adjusted
      r-square of 0.89 and root-mean square error of 2.52 d. The model provides the
      means to disentangle the environmental dependencies of complex traits, and
      presents an opportunity to identify in silico QTL allele combinations that could
      yield desired phenotypes under different climatic conditions.

PMID- 29025917
TI  - SID-1 Domains Important for dsRNA Import in Caenorhabditis elegans.
AB  - In the nematode Caenorhabditis elegans, RNA interference (RNAi) triggered by
      double-stranded RNA (dsRNA) spreads systemically to cause gene silencing
      throughout the organism and its progeny. We confirm that Caenorhabditis nematode
      SID-1 orthologs have dsRNA transport activity and demonstrate that the SID-1
      paralog CHUP-1 does not transport dsRNA. Sequence comparison of these similar
      proteins, in conjunction with analysis of loss-of-function missense alleles,
      identifies several conserved 2-7 amino acid microdomains within the extracellular
      domain (ECD) that are important for dsRNA transport. Among these missense
      alleles, we identify and characterize a sid-1 allele, qt95, which causes tissue
      specific silencing defects most easily explained as a systemic RNAi export
      defect. However, we conclude from genetic and biochemical analyses that sid
      1(qt95) disrupts only import, and speculate that the apparent export defect is
      caused by the cumulative effect of sequentially impaired dsRNA import steps.
      Thus, consistent with previous studies, we fail to detect a requirement for sid-1
      in dsRNA export, but demonstrate for the first time that SID-1 functions in the
      intestine to support environmental RNAi (eRNAi).

PMID- 29025919
TI  - Adult-onset biotinidase deficiency: two individuals with severe, but reversible
      optic neuropathy.

PMID- 29025920
TI  - Heartbeat: Glycaemic control and excess risk of major coronary events in type 1
      diabetes.

PMID- 29025921
TI  - Phosphodiesterase-5 inhibitors as novel cardioprotective agents: have we reached
      threshold for large-scale clinical trials?

PMID- 29025922
TI  - The results of a pharmacoeconomic study: incremental cost-effectiveness ratio
      versus net monetary benefit.

PMID- 29025925
TI  - Strength of Temporal White Matter Pathways Predicts Semantic Learning.
AB  - Learning the associations between words and meanings is a fundamental human
      ability. Although the language network is cortically well defined, the role of
      the white matter pathways supporting novel word-to-meaning mappings remains
      unclear. Here, by using contextual and cross-situational word learning, we tested
      whether learning the meaning of a new word is related to the integrity of the
      language-related white matter pathways in 40 adults (18 women). The arcuate,
      uncinate, inferior-fronto-occipital and inferior-longitudinal fasciculi were
      virtually dissected using manual and automatic deterministic fiber tracking.
      Critically, the automatic method allowed assessing the white matter
      microstructure along the tract. Results demonstrate that the microstructural
      properties of the left inferior-longitudinal fasciculus predict contextual
      learning, whereas the left uncinate was associated with cross-situational
      learning. In addition, we identified regions of special importance within these
      pathways: the posterior middle temporal gyrus, thought to serve as a lexical
      interface and specifically related to contextual learning; the anterior temporal
      lobe, known to be an amodal hub for semantic processing and related to cross
      situational learning; and the white matter near the hippocampus, a structure
      fundamental for the initial stages of new-word learning and, remarkably, related
      to both types of word learning. No significant associations were found for the
      inferior-fronto-occipital fasciculus or the arcuate. While previous results
      suggest that learning new phonological word forms is mediated by the arcuate
      fasciculus, these findings show that the temporal pathways are the crucial neural
      substrate supporting one of the most striking human abilities: our capacity to
      identify correct associations between words and meanings under referential
      indeterminacy.SIGNIFICANCE STATEMENT The language-processing network is
      cortically (i.e., gray matter) well defined. However, the role of the white
      matter pathways that support novel word learning within this network remains
      unclear. In this work, we dissected language-related (arcuate, uncinate, inferior
      fronto-occipital, and inferior-longitudinal) fasciculi using manual and automatic
      tracking. We found the left inferior-longitudinal fasciculus to be predictive of
      word-learning success in two word-to-meaning tasks: contextual and cross
      situational learning paradigms. The left uncinate was predictive of cross
      situational word learning. No significant correlations were found for the arcuate
      or the inferior-fronto-occipital fasciculus. While previous results showed that
      learning new phonological word forms is supported by the arcuate fasciculus,
      these findings demonstrate that learning new word-to-meaning associations is
      mainly dependent on temporal white matter pathways.

PMID- 29025923
TI  - Plasticity of Signaling by Spinal Estrogen Receptor alpha, kappa-Opioid Receptor,
      and Metabotropic Glutamate Receptors over the Rat Reproductive Cycle Regulates
      Spinal Endomorphin 2 Antinociception: Relevance of Endogenous-Biased Agonism.
AB  - We previously showed that intrathecal application of endomorphin 2 [EM2; the
      highly specific endogenous MU-opioid receptor (MOR) ligand] induces
      antinociception that varies with stage of the rat estrous cycle: minimal during
      diestrus and prominent during proestrus. Earlier studies, however, did not
      identify proestrus-activated signaling strategies that enable spinal EM2
      antinociception. We now report that in female rats, increased spinal dynorphin
      release and kappa-opioid receptor (KOR) signaling, as well as the emergence of
      glutamate-activated metabotropic glutamate receptor 1 (mGluR1) signaling, are
      critical to the transition from an EM2 nonresponsive state (during diestrus) to
      an analgesically responsive state (during proestrus). Differential signaling by
      mGluR1, depending on its activation by membrane estrogen receptor alpha
      (mERalpha; during diestrus) versus glutamate (during proestrus), concomitant with
      the ebb and flow of spinal dynorphin/KOR signaling, functions as a switch,
      preventing or promoting, respectively, spinal EM2 antinociception. Importantly,
      EM2 and glutamate-containing varicosities appose spinal neurons that express MOR
      along with mGluRs and mERalpha, suggesting that signaling mechanisms regulating
      analgesic effectiveness of intrathecally applied EM2 also pertain to endogenous
      EM2. Regulation of spinal EM2 antinociception by both the nature of the
      endogenous mGluR1 activator (i.e., endogenous biased agonism at mGluR1) and
      changes in spinal dynorphin/KOR signaling represent a novel mechanism for
      modulating analgesic responsiveness to endogenous EM2 (and perhaps other
      opioids). This points the way for developing noncanonical pharmacological
      approaches to pain management by harnessing endogenous opioids for pain
      relief.SIGNIFICANCE STATEMENT The current prescription opioid abuse epidemic
      underscores the urgency to develop alternative pharmacotherapies for managing
      pain. We find that the magnitude of spinal endomorphin 2 (EM2) antinociception
      not only varies with stage of reproductive cycle, but is also differentially
      regulated during diestrus and proestrus. This finding highlights the need for sex
      specific and cycle-specific approaches to pain management. Additionally, our
      finding that spinal EM2 antinociception in female rats is regulated by both the
      ebb and flow of spinal dynorphin/kappa-opioid receptor signaling over the estrous
      cycle, as well as the nature of the endogenous mGluR1 activator, could encourage
      noncanonical pharmacological approaches to pain management, such as harnessing
      endogenous opioids for pain relief.

PMID- 29025924
TI  - Dmrt5, a Novel Neurogenic Factor, Reciprocally Regulates Lhx2 to Control the
      Neuron-Glia Cell-Fate Switch in the Developing Hippocampus.
AB  - Regulation of the neuron-glia cell-fate switch is a critical step in the
      development of the CNS. Previously, we demonstrated that Lhx2 is a necessary and
      sufficient regulator of this process in the mouse hippocampal primordium, such
      that Lhx2 overexpression promotes neurogenesis and suppresses gliogenesis,
      whereas loss of Lhx2 has the opposite effect. We tested a series of transcription
      factors for their ability to mimic Lhx2 overexpression and suppress baseline
      gliogenesis, and also to compensate for loss of Lhx2 and suppress the resulting
      enhanced level of gliogenesis in the hippocampus. Here, we demonstrate a novel
      function of Dmrt5/Dmrta2 as a neurogenic factor in the developing hippocampus. We
      show that Dmrt5, as well as known neurogenic factors Neurog2 and Pax6, can each
      not only mimic Lhx2 overexpression, but also can compensate for loss of Lhx2 to
      different extents. We further uncover a reciprocal regulatory relationship
      between Dmrt5 and Lhx2, such that each can compensate for loss of the other.
      Dmrt5 and Lhx2 also have opposing regulatory control on Pax6 and Neurog2,
      indicating a complex bidirectionally regulated network that controls the neuron
      glia cell-fate switch.SIGNIFICANCE STATEMENT We identify Dmrt5 as a novel
      regulator of the neuron-glia cell-fate switch in the developing hippocampus. We
      demonstrate Dmrt5 to be neurogenic, and reciprocally regulated by Lhx2: loss of
      either factor promotes gliogenesis; overexpression of either factor suppresses
      gliogenesis and promotes neurogenesis; each can substitute for loss of the other.
      Furthermore, each factor has opposing effects on established neurogenic genes
      Neurog2 and Pax6 Dmrt5 is known to suppress their expression, and we show that
      Lhx2 is required to maintain it. Our study reveals a complex regulatory network
      with bidirectional control of a fundamental feature of CNS development, the
      control of the production of neurons versus astroglia in the developing
      hippocampus.Finally, we confirm that Lhx2 binds a highly conserved putative
      enhancer of Dmrt5, suggesting an evolutionarily conserved regulatory relationship
      between these factors. Our findings uncover a complex network that involves Lhx2,
      Dmrt5, Neurog2, and Pax6, and that ensures the appropriate amount and timing of
      neurogenesis and gliogenesis in the developing hippocampus.

PMID- 29025927
TI  - Genome Sequence of Fowl Aviadenovirus A Strain JM1/1, Which Caused Gizzard
      Erosions in Japan.
AB  - This study reports the complete genome sequence of fowl aviadenovirus A strain
      JM1/1, which caused gizzard erosions in broilers occurring in Japan. The JM1/1
      genome is 43,809 bp in length and most closely related to the strain chicken
      embryo lethal orphan (CELO); moreover, multiple site insertions and deletions
      were found.

PMID- 29025926
TI  - Enhancing Spinal Plasticity Amplifies the Benefits of Rehabilitative Training and
      Improves Recovery from Stroke.
AB  - The limited recovery that occurs following stroke happens almost entirely in the
      first weeks postinjury. Moreover, the efficacy of rehabilitative training is
      limited beyond this narrow time frame. Sprouting of spared corticospinal tract
      axons in the contralesional spinal cord makes a significant contribution to
      sensorimotor recovery, but this structural plasticity is also limited to the
      first few weeks after stroke. Here, we tested the hypothesis that inducing
      plasticity in the spinal cord during chronic stroke could improve recovery from
      persistent sensorimotor impairment. We potentiated spinal plasticity during
      chronic stroke, weeks after the initial ischemic injury, in male Sprague-Dawley
      rats via intraspinal injections of chondroitinase ABC. Our data show that
      chondroitinase injections into the contralesional gray matter of the cervical
      spinal cord administered 28 d after stroke induced significant sprouting of
      corticospinal axons originating in the peri-infarct cortex. Chondroitinase ABC
      injection during chronic stroke without additional training resulted in moderate
      improvements of sensorimotor deficits. Importantly, this therapy dramatically
      potentiated the efficacy of rehabilitative training delivered during chronic
      stroke in a skilled forelimb reaching task. These novel data suggest that spinal
      therapy during chronic stroke can amplify the benefits of delayed rehabilitative
      training with the potential to reduce permanent disability in stroke
      survivors.SIGNIFICANCE STATEMENT The brain and spinal cord undergo adaptive
      rewiring ("plasticity") following stroke. This plasticity allows for partial
      functional recovery from stroke induced sensorimotor impairments. However, the
      plasticity that underlies recovery occurs predominantly in the first weeks
      following stroke, and most stroke survivors are left with permanent disability
      even after rehabilitation. Using animal models, our data show that removal of
      plasticity-inhibiting signals in the spinal cord (via intraspinal injections of
      the enzyme chondroitinase ABC) augments rewiring of circuits connecting the brain
      to the spinal cord, even weeks after stroke. Moreover, this plasticity can be
      harnessed by rehabilitative training to significantly promote sensorimotor
      recovery. Thus, intraspinal therapy may augment rehabilitative training and
      improve recovery even in individuals living with chronic disability due to
      stroke.

PMID- 29025928
TI  - Draft Genome Sequence of Lactobacillus plantarum Strain A6, a Strong Acid
      Producer Isolated from a Vietnamese Fermented Sausage (Nem Chua).
AB  - Lactobacillus plantarum strain A6, a strong acid producer, was isolated from a
      Vietnamese fermented sausage (nem chua). Here, we report the genome sequence of
      this strain (3,368,579 bp).

PMID- 29025929
TI  - Whole-Genome Sequence of Bifidobacterium longum Strain Indica, Isolated from the
      Gut of a Healthy Indian Adult.
AB  - Bifidobacterium longum, a Gram-positive rod-shaped anaerobic bacterium, inhabits
      the human gastrointestinal tract and contributes significantly to oligosaccharide
      production, amino acid metabolism, and protection against intestinal
      inflammation. Here, we report the whole-genome sequence of B. longum, which was
      isolated from the gastrointestinal tract of a healthy Indian adult.

PMID- 29025930
TI  - Draft Genome Sequence of a Picorna-Like Virus Associated with Gill Tissue in
      Clinically Normal Brook Trout, Salvelinus fontinalis.
AB  - Here, we report a draft genome sequence of a picorna-like virus associated with
      brook trout, Salvelinus fontinalis, gill tissue. The draft genome comprises 8,681
      nucleotides, excluding the poly(A) tract, and contains two open reading frames.
      It is most similar to picorna-like viruses that infect invertebrates.

PMID- 29025931
TI  - Complete Genome Sequence of a Porcine Epidemic Diarrhea Virus Isolated in
      Belgorod, Russia, in 2008.
AB  - We identified porcine epidemic diarrhea virus (PEDV) in stool samples from sick
      piglets in the Belgorod region of Russia. The complete coding genome sequence of
      28,295 nucleotides (nt) of PEDV was generated. Compared to a prototype PEDV
      strain (DR13), an extreme number of mismatches in the S gene were revealed.

PMID- 29025932
TI  - Chloroplast Genome Sequences of Seven Strains of the Bloom-Forming Raphidophyte
      Heterosigma akashiwo.
AB  - We report here the complete chloroplast genome sequences of seven strains of the
      bloom-forming raphidophyte Heterosigma akashiwo These ~160-kb sequences contain
      124 protein-, 6 rRNA-, and 34 tRNA-coding sequences. Notable sequence variations
      were observed among these seven sequenced and two previously characterized
      strains.

PMID- 29025933
TI  - Complete Genome Sequences of Four Brucella Strains Isolated from China.
AB  - Brucella spp. are facultative intracellular pathogens that cause a contagious
      zoonotic disease. Twelve different species are currently identified. This study
      presents the complete genome sequences of four Brucella strains. These complete
      genomes were annotated and the contents compared to those of other strains
      isolated from China.

PMID- 29025934
TI  - Draft Genome Sequence of Salmonella enterica Serovar Senftenberg 070885 and Its
      Linalool-Adapted Mutant.
AB  - Here we report the genome sequences of both Salmonella Senftenberg 070885, a
      clinical isolate from the 2007 outbreak linked to basil, and its mutant linalool
      adapted S Senftenberg (LASS). These draft genomes of S Senftenberg may enable the
      identification of bacterial genes responsible for resistance to basil oil.

PMID- 29025935
TI  - Two Complete Sequences for Genomes of Human Respiratory Syncytial Virus Genotype
      ON1 Field Strains from Beijing, China.
AB  - Here, we report the complete sequences for genomes of two human respiratory
      syncytial virus field strains. It was determined by sequence alignment and
      phylogenetics that they belong to genotype ON1, characterized by a 72-nucleotide
      duplication in the C termini of the attachment protein G genes.

PMID- 29025936
TI  - Complete Genome Sequence of Super Biofilm-Elaborating Staphylococcus aureus
      Isolated in Japan.
AB  - Staphylococcus aureus JP080, previously named TF2758, is a clinical isolate from
      an atheroma and a super biofilm-elaborating strain whose biofilm elaboration is
      dependent solely on polysaccharide poly-N-acetylglucosamine/polysaccharide
      intercellular adhesin (PNAG/PIA). Here, we report the complete genome sequence of
      strain JP080, which consists of one chromosome and one circular plasmid.

PMID- 29025938
TI  - Draft Genome Sequence of Bacillus velezensis GF610, a Producer of Potent Anti
      Listeria Agents.
AB  - Bacillus velezensis GF610 was isolated from soil in Illinois, USA, and found to
      produce amyloliquecidin GF610, a potent two-component antimicrobial peptide. We
      report here the GF610 strain draft genome sequence, which contains 4.29 Mb and an
      overall GC content of 45.91%.

PMID- 29025937
TI  - Draft Genome Sequence of Romboutsia maritimum sp. nov. Strain CCRI-22766T,
      Isolated from Coastal Estuarine Mud.
AB  - The Romboutsia maritimum sp. nov. CCRI-22766T strain was isolated from coastal
      estuarine mud in New Zealand. The genome assembly comprised 2,854,352 bp, with
      27.1% G+C content. This is the first documentation that reports the genome
      sequence of R. maritimum.

PMID- 29025939
TI  - Draft Genome Sequences of Two Novel Sub-Antarctic Williamsia Species.
AB  - Illumina MiSeq shotgun sequencing technology was used to sequence the genomes of
      two novel sub-Antarctic Williamsia species, designated strains 1135 and 1138. The
      estimated genome sizes for strains 1135 and 1138 are 5.99 Mb and 6.08 Mb,
      respectively. This genome sequence information will aid in understanding the
      lipid metabolic pathways of cold-tolerant Williamsia species.

PMID- 29025940
TI  - Detection and Whole-Genome Analysis of a Zoonotic G8P[14] Rotavirus Strain
      Isolated from a Child with Diarrhea.
AB  - The group A rotavirus strain SI-2987/09 was detected in a child with severe
      diarrhea. The whole-genome analysis revealed the G8-P[14]-I2-R2-C2-M2-A3-N2-T6-E2
      H3 genome constellation, which reflects the zoonotic transmission of the strain
      most probably from the ungulate group. This was also confirmed by the high
      nucleotide identity to those animal rotavirus strains.

PMID- 29025941
TI  - Draft Genome Sequence of a Rare Pigmented Mycobacterium avium subsp.
      paratuberculosis Type C Strain.
AB  - Mycobacterium avium subsp. paratuberculosis is the causative agent of
      paratuberculosis. We report here the draft genome sequence of a rare pigmented M.
      avium subsp. paratuberculosis type C strain, comprising 58 contigs and having a
      genome size of 4,851,414 bp. The genome will assist in the execution of
      pigmentation and virulence studies on this mycobacterium.

PMID- 29025942
TI  - Complete Genome Sequence of Porphyrobacter sp. Strain CACIAM 03H1, a
      Proteobacterium Obtained from a Nonaxenic Culture of Microcystis aeruginosa.
AB  - Here, we present a complete genome sequence and annotation of Porphyrobacter sp.
      strain CACIAM 03H1, which was obtained from a nonaxenic culture of Microcystis
      aeruginosa, a cyanobacterium isolated from an Amazonian freshwater environment.

PMID- 29025943
TI  - Draft Genome Sequence of Bacillus aryabhattai Strain PHB10, a Poly(3
      Hydroxybutyrate)-Accumulating Bacterium Isolated from Domestic Sewerage.
AB  - Bacillus aryabhattai PHB10 is a poly(3-hydroxybutyrate) (PHB)-accumulating
      bacterium isolated from domestic sewerage. Here, we report the 4.19-Mb draft
      genome sequence, with 4,050 protein-coding genes and a G+C content of 37.5%. This
      sequence will be helpful in the study of the high-level PHB accumulation
      mechanism of the strain.

PMID- 29025944
TI  - Draft Genome Sequences of Nine Livestock-Associated Methicillin-Resistant
      Staphylococcus aureus Sequence Type 5 Isolates from Humans with Long-Term Swine
      Contact.
AB  - Humans have been found to harbor livestock-associated methicillin-resistant
      Staphylococcus aureus (LA-MRSA) isolates. LA-MRSA isolates are considered adapted
      to colonizing livestock and less pathogenic in humans than their hospital- and
      community-acquired counterparts. Here, we present nine LA-MRSA sequence type 5
      isolates from veterinarians with long-term swine contact.

PMID- 29025945
TI  - Draft Genome Sequences of Nine Livestock-Associated Methicillin-Resistant
      Staphylococcus aureus Sequence Type 5 Isolates Obtained from Humans after Short
      Term Swine Contact.
AB  - Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA)
      sequence type 5 (ST5) has raised concerns surrounding the potential for these
      isolates to colonize or cause disease in humans with swine contact. Here, we
      report draft genome sequences for nine LA-MRSA ST5 isolates obtained from humans
      after short term swine contact.

PMID- 29025946
TI  - Complete Genome Sequence of Peste des Petits Ruminants Virus from Georgia, 2016.
AB  - We report here the complete genome sequence of a peste des petits ruminants virus
      (PPRV) from the first outbreak of the disease in Georgia in January 2016. Genome
      sequencing was performed using Illumina next-generation sequencing technology in
      conjunction with Sanger sequencing. This PPRV/Georgia/Tbilisi/2016 genome
      sequence clustered within lineage IV PPRV viruses.

PMID- 29025948
TI  - Genome Sequences of Coxsackievirus B5 Isolates from Two Children with Meningitis
      in Australia.
AB  - Two coxsackievirus B5 (CVB5) strains were isolated from two children with aseptic
      meningitis in Australia. Their genomes were sequenced and found to be divergent
      from the previously reported CVB5 genome sequences, with both having 84% and 97%
      identities to the closest strains at the nucleotide and amino acid levels,
      respectively.

PMID- 29025947
TI  - Draft Genome Sequence of Brevibacillus laterosporus OSY-I1, a Strain That
      Produces Brevibacillin, Which Combats Drug-Resistant Gram-Positive Bacteria.
AB  - Brevibacillus laterosporus OSY-I1 is a Gram-positive spore-forming bacterium
      isolated from soil. The bacterium produces brevibacillin, an antimicrobial
      lipopeptide effective against several drug-resistant Gram-positive bacteria.
      Here, we present the draft genome sequence of the strain OSY-I1 and the gene
      cluster responsible for the biosynthesis of brevibacillin.

PMID- 29025949
TI  - Genome Sequence of Saccharomyces cerevisiae Strain Kagoshima No. 2, Used for
      Brewing the Japanese Distilled Spirit Shochu.
AB  - Here, we report a draft genome sequence of Saccharomyces cerevisiae strain
      Kagoshima no. 2, which is used for brewing shochu, a traditional distilled spirit
      in Japan. The genome data will facilitate an understanding of the evolutional
      traits and genetic background related to the characteristic features of strain
      Kagoshima no. 2.

PMID- 29025951
TI  - Erratum for Orr et al., "Draft Genome Sequences of Two Unclassified
      Chitinophagaceae Bacteria, IBVUCB1 and IBVUCB2, Isolated from Environmental
      Samples".

PMID- 29025950
TI  - High-Quality Draft Genome Sequence of Burkholderia contaminans CH-1, a Gram
      Negative Bacterium That Metabolizes 2-Azahypoxanthine, a Plant Growth-Regulating
      Compound.
AB  - Burkholderia contaminans strain CH-1 converts 2-azahypoxnathine to 2-aza-8
      oxohypoxanthine, plant growth-regulating compounds, by oxidation. We report here
      the high-quality draft genome sequence of B. contaminans CH-1. The genome
      contains 8,065 protein-coding sequences, including several genes possibly
      involved in metabolizing 2-azahypoxanthine.

PMID- 29025952
TI  - Permanent Draft Genome Sequences for Mesorhizobium sp. Strains LCM 4576, LCM
      4577, and ORS3428, Salt-Tolerant, Nitrogen-Fixing Bacteria Isolated from
      Senegalese Soils.
AB  - The genus Mesorhizobium contains many species that are able to form nitrogen
      fixing nodules on plants of the legume family. Here, we report the draft genome
      sequences for three Mesorhizobium strains. The genome sizes of strains LCM 4576,
      LCM 4577, and ORS3428 were 7.24, 7.02, and 6.55 Mbp, respectively.

PMID- 29025953
TI  - Complete Genome Sequence of Lactobacillus plantarum Oregon-R-modENCODE Strain
      BDGP2 Isolated from Drosophila melanogaster Gut.
AB  - Lactobacillus plantarum Oregon-R-modENCODE strain BDGP2 was isolated from the gut
      of Drosophila melanogaster for functional host microbial interaction studies. The
      complete genome comprised a single circular genome of 3,407,160 bp, with a G+C
      content of 44%, and four plasmids.

PMID- 29025954
TI  - Three Draft Genome Sequences of Vibrio coralliilyticus Strains Isolated from
      Bivalve Hatcheries.
AB  - Reported here are the genome sequences of three Vibrio coralliilyticus isolates
      RE87, AIC-7, and 080116A. Each strain was isolated in association with oyster
      larvae in commercial aquaculture systems. These draft genomes will be useful for
      further studies in understanding the genomic features contributing to V.
      coralliilyticus pathogenicity.

PMID- 29025955
TI  - Genome Sequence of Pseudomonas putida Strain ASAD, an Acetylsalicylic Acid
      Degrading Bacterium.
AB  - Pseudomonas putida strain ASAD was isolated from compost because of its ability
      to utilize aspirin (acetylsalicylic acid) as a carbon and energy source. We
      report the draft genome sequence of strain ASAD, with an estimated length of 6.9
      Mb. Study of this isolate will provide insight into the aspirin biodegradation
      pathway.

PMID- 29025956
TI  - Erratum for Orr et al., "Draft Genome Sequences of Two Unclassified Bacteria,
      Sphingomonas sp. Strains IBVSS1 and IBVSS2, Isolated from Environmental Samples".

PMID- 29025957
TI  - Admissions to Acute Care Within 30 and 90 Days of Discharge Home From a Pediatric
      Post-acute Care Hospital.
AB  - OBJECTIVES: Of all hospitalized children, those with medical complexity have the
      highest likelihood of hospital readmission. Post-acute hospital care could
      potentially help stabilize the health of these children. We examined the
      frequency of acute care hospital admissions after discharge home from a post
      acute care hospital (PACH). METHODS: A retrospective cohort analysis of 448
      children with medical complexity discharged from a PACH from January 1, 2010, to
      December 31, 2015, with the main outcomes of acute care hospital readmissions 0
      to 30 and 31 to 90 days after discharge home from a PACH. Demographic and
      clinical characteristics were compared between children with and without acute
      care readmission and between the 2 readmission groups. RESULTS: Ninety-nine
      children (22%) had a readmission to the acute care hospital. Of these
      readmissions, 61 (62%) occurred between 0 and 30 days and 38 (38%) between 31 and
      90 days after PACH discharge. A higher percentage of children readmitted had high
      medical severity (>3 systems involved or ventilator dependent) compared with
      children not readmitted (68% vs 31%, P = .04). No differences were found between
      children who were readmitted and those who were not by sex, race, payer, length
      of stay, or age at PACH discharge. Additionally, no differences were found
      between children readmitted within 30 days and children readmitted 31 to 90 days
      after PACH discharge. CONCLUSIONS: The majority of children discharged home from
      a PACH do not require an acute care hospitalization within the first 3 months.
      Children with greater medical severity are readmitted more often than others.

PMID- 29025959
TI  - Challenges to improving occupational health in China.

PMID- 29025958
TI  - miR-34a Regulates Expression of the Stathmin-1 Oncoprotein and Prostate Cancer
      Progression.
AB  - In aggressive prostate cancers, the oncoprotein STMN1 (also known as stathmin 1
      and oncoprotein 18) is often overexpressed. STMN1 is involved in various cellular
      processes, including cell proliferation, motility, and tumor metastasis. Here, it
      was found that the expression of STMN1 RNA and protein is elevated in metastatic
      prostate cancers. Knockdown of STMN1 resulted in reduced proliferation and
      invasion of cells and tumor growth and metastasis in vivo Furthermore, miR-34a
      downregulated STMN1 by directly binding to its 3'-UTR. Overexpression of miR-34a
      in prostate cancer cells reduced proliferation and colony formation, suggesting
      that it is a tumor suppressor. The transcriptional corepressor C-terminal binding
      protein 1 (CtBP1) negatively regulated expression of miR-34a. Furthermore, gene
      expression profiling of STMN1-modulated prostate cancer cells revealed molecular
      alterations, including elevated expression of growth differentiation factor 15
      (GDF15), which is involved in cancer progression and potentially in STMN1
      mediated oncogenesis. Thus, in prostate cancer, CtBP1-regulated miR-34a modulates
      STMN1 expression and is involved in cancer progression through the CtBP1?miR
      34a?STMN1?GDF15 axis.Implications: The CtBP1?miR-34a?STMN1?GDF15 axis is a
      potential therapeutic target for treatment of aggressive prostate cancer. Mol
      Cancer Res; 16(7); 1125-37. (c)2017 AACR.

PMID- 29025962
TI  - Therapeutic hypothermia in acute traumatic spinal cord injury.
AB  - Therapeutic hypothermia is already widely acknowledged as an effective
      neuroprotective intervention, especially within the acute care setting in
      relation to conditions such as cardiac arrest and neonatal encephalopathy. Its
      multifactorial mechanisms of action, including lowering metabolic rate and
      reducing acute inflammatory cellular processes, ultimately provide protection for
      central nervous tissue from continuing injury following ischaemic or traumatic
      insult. Its clinical application within acute traumatic spinal cord injury would
      therefore seem very plausible, it having the potential to combat the
      pathophysiological secondary injury processes that can develop in the proceeding
      hours to days following the initial injury. As such it could offer invaluable
      assistance to lessen subsequent sensory, motor and autonomic dysfunction for an
      individual affected by this devastating condition. Yet research surrounding this
      intervention's applicability in this field is somewhat lacking, the majority
      being experimental. Despite a recent resurgence of interest, which in turn has
      produced encouraging results, there is a real possibility that this potentially
      transformational intervention for treating traumatic spinal cord injury could
      remain an experimental therapy and never reach clinical implementation.

PMID- 29025960
TI  - De Novo Assembly of a New Solanum pennellii Accession Using Nanopore Sequencing.
AB  - Updates in nanopore technology have made it possible to obtain gigabases of
      sequence data. Prior to this, nanopore sequencing technology was mainly used to
      analyze microbial samples. Here, we describe the generation of a comprehensive
      nanopore sequencing data set with a median read length of 11,979 bp for a self
      compatible accession of the wild tomato species Solanum pennellii We describe the
      assembly of its genome to a contig N50 of 2.5 MB. The assembly pipeline comprised
      initial read correction with Canu and assembly with SMARTdenovo. The resulting
      raw nanopore-based de novo genome is structurally highly similar to that of the
      reference S. pennellii LA716 accession but has a high error rate and was rich in
      homopolymer deletions. After polishing the assembly with Illumina reads, we
      obtained an error rate of <0.02% when assessed versus the same Illumina data. We
      obtained a gene completeness of 96.53%, slightly surpassing that of the reference
      S. pennellii Taken together, our data indicate that such long read sequencing
      data can be used to affordably sequence and assemble gigabase-sized plant
      genomes.

PMID- 29025961
TI  - Phosphate replacement in the critically ill: potential implications for military
      patients.
AB  - BACKGROUND: Severe hypophosphataemia in the intensive care unit (ICU) setting has
      been widely associated with adverse clinical outcomes across multiple organ
      systems, as well as increased mortality. However, the clinical significance of
      mild or moderate hypophosphataemia remains uncertain. This can lead to
      heterogeneous phosphate replacement protocols across different institutions. The
      aim of this study was to assess the significance of mild and moderate
      hypophosphataemia on clinical outcomes across several organ systems. METHOD: All
      patients over a 3-week period in our ICU were retrospectively analysed with
      admission serum phosphate compared with subsequent clinical outcomes after
      admission. Low serum phosphate (0.3-1.0 mmol/L), according to local protocol, was
      compared with normal serum phosphate (>1.0 mmol/L). RESULTS: Of the 72 patients
      admitted to intensive therapy unit during this period, 14/72 (19%) had phosphate
      levels deemed low (<1.0 mmol/L) and received phosphate supplementation. No
      significant difference was found between groups in terms of cardiac arrhythmias
      (p=0.55), capillary blood glucose (p=0.08) and serum lactate (p=0.32). Low
      phosphate (0.3-1.0 mmol/L) was not associated with increased likelihood of
      requiring ventilation. Platelet count was significantly lower in the low
      phosphate group (p=0.008). CONCLUSION: In our study, mild and moderate
      hypophosphataemia was not associated with adverse clinical outcome across most
      organ systems analysed. Given the current evidence and results of this study, we
      would suggest that there is a trend towards over-replacement of phosphate,
      representing a potential clinical safety issue as well as clear financial
      implications.

PMID- 29025963
TI  - Sacral dural arteriovenous fistulas: a diagnostic and therapeutic challenge -
      single-centre experience of 13 cases and review of the literature.
AB  - BACKGROUND: Sacral dural arteriovenous fistulas (DAVFs) are rare vascular
      abnormalities of the spine characterised by slowly progressive symptoms that can
      mimic different myelopathy disorders. OBJECT: To report our single Institution
      experience with sacral DAVFs. METHODS: We retrospectively reviewed the clinical
      records of patients admitted from 1 January 2006 to 31 December 2016 with a
      diagnosis of sacral DAVFs, treated by endovascular embolisation or surgical
      clipping. Clinical presentation, imaging characteristics, treatment results and
      follow-up were analysed. RESULTS: We identify 13 patients with sacral DAVFs
      supplied by lateral sacral arteries. Clinical presentation was characterised by
      different degrees of motor weakness and sphincter disturbances. In all patients,
      spinal MRI showed spinal cord hyperintensities with enhancement and prominent
      perimedullary vessels. Selective internal iliac angiography was mandatory to
      identify the exact location of the fistula. A complete embolisation was achieved
      in eight patients performing a single endovascular embolisation and in three
      patients performing a single surgical disconnection: two patients required
      combined procedures. Follow-up imaging showed a complete resolution of the spinal
      cord hyperintensities in 81% of patients and a reduction of the intramedullary
      enhancement in 91%. Gait improvement was observed in 73% of patients, while
      remaining stable in 27%. Sphincter disturbances improved in 36% of patients and
      remained stable in 64%. CONCLUSION: Awareness of sacral location of DAVFs is
      critical because standard spinal angiography will not identify sacral supplies,
      unless internal iliac arteries are properly examined. In our experience, the
      endovascular treatment show results comparable to surgery when the fistula point
      is correctly disconnected.

PMID- 29025964
TI  - False-Positive Newborn Screening for Cystic Fibrosis and Health Care Use.
AB  - OBJECTIVES: Evidence is mixed regarding the impact of false-positive (FP) newborn
      bloodspot screening (NBS) results on health care use. Using cystic fibrosis (CF)
      as an example, we determined the association of FP NBS results with health care
      use in infants and their mothers in Ontario, Canada. METHODS: We conducted a
      population-based cohort study of all infants with FP CF results (N = 1564) and
      screen-negative matched controls (N = 6256) born between April 2008 and November
      2012 using linked health administrative data. Outcomes included maternal and
      infant physician and emergency visits and inpatient hospitalizations from the
      infant's third to 15th month of age. Negative binomial regression tested
      associations of NBS status with outcomes, adjusting for infant and maternal
      characteristics. RESULTS: A greater proportion of infants with FP results had >2
      outpatient visits (16.2% vs 13.2%) and >2 hospital admissions (1.5% vs 0.7%)
      compared with controls; CF-related admissions and emergency department visits
      were not different from controls. Differences persisted after adjustment, with
      higher rates of outpatient visits (relative risk 1.39; 95% confidence interval
      1.20-1.60) and hospital admissions (relative risk 1.67; 95% confidence interval
      1.21-2.31) for FP infants. Stratified models indicated the effect of FP status
      was greater among those whose primary care provider was a pediatrician. No
      differences in health care use among mothers were detected. CONCLUSIONS: Higher
      use of outpatient services among FP infants may relate to a lengthy confirmatory
      testing process or follow-up carrier testing. However, increased rates of
      hospitalization might signal heightened perceptions of vulnerability among
      healthy infants.

PMID- 29025966
TI  - Notch Signaling: Linking Embryonic Lung Development and Asthmatic Airway
      Remodeling.
AB  - Lung development is mediated by assorted signaling proteins and orchestrated by
      complex mesenchymal-epithelial interactions. Notch signaling is an evolutionarily
      conserved cell-cell communication mechanism that exhibits a pivotal role in lung
      development. Notably, both aberrant expression and loss of regulation of Notch
      signaling are critically linked to the pathogenesis of various lung diseases, in
      particular, pulmonary fibrosis, lung cancer, pulmonary arterial hypertension, and
      asthmatic airway remodeling; implying that precise regulation of intensity and
      duration of Notch signaling is imperative for appropriate lung development.
      Moreover, evidence suggests that Notch signaling links embryonic lung development
      and asthmatic airway remodeling. Herein, we summarized all-recent advances
      associated with the mechanistic role of Notch signaling in lung development,
      consequences of aberrant expression or deletion of Notch signaling in linking
      early-impaired lung development and asthmatic airway remodeling, and all recently
      investigated potential therapeutic strategies to treat asthmatic airway
      remodeling.

PMID- 29025965
TI  - Inherited IL-12Rbeta1 Deficiency in a Child With BCG Adenitis and Oral
      Candidiasis: A Case Report.
AB  - Tuberculosis is a major worldwide problem, and protection from it is achieved
      mainly by live attenuated bacille Calmette-Guerin vaccine, which is capable of
      causing disease in immunocompromised host. Oral thrush is abnormal in healthy
      children, which suggests an underlying immunodeficiency. Mendelian susceptibility
      to mycobacterial disease is a rare primary immunodeficiency characterized by a
      selective predisposition to weakly virulent Mycobacteria and Salmonella and also
      predisposition to chronic mucocutaneous candidiasis. Interleukin 12 receptor
      beta1 (IL-12Rbeta1) deficiency is the most common disease of Mendelian
      susceptibility to mycobacterial disease, and to date only 50 IL-12Rbeta1
      deficient patients with clinical signs of chronic mucocutaneous candidiasis have
      been reported. We report a 2.5-year-old daughter of consanguineous parents with
      both regional bacille Calmette-Guerin lymphadenitis and recurrent oral
      candidiasis carrying biallelic R175W mutation in the IL12RB1 gene, resulting in
      complete loss of expression of IL-12Rbeta1. To our knowledge, this is the first
      report of bacille Calmette-Guerin lymphadenitis with concurrent oral candidiasis
      displaying such a mutation. New mutations and wide clinical diversities are the
      indisputable fact of populations with a high rate of consanguineous marriages.

PMID- 29025967
TI  - Diminazene Is a Slow Pore Blocker of Acid-Sensing Ion Channel 1a (ASIC1a).
AB  - Acid-sensing ion channels (ASICs) are neuronal receptors for extracellular
      protons. They contribute to the excitatory postsynaptic current and to the
      detection of painful acidosis. Moreover, they are activated during peripheral
      inflammation and acidosis associated with various neuronal disorders, such as
      stroke and neuroinflammation, rendering them interesting drug targets. Diminazene
      aceturate is a small-molecule inhibitor of ASICs with a reported apparent
      affinity in the low micromolar range, making it an interesting lead compound. It
      was reported that diminazene accelerates desensitization of ASICs, which was,
      however, not explained mechanistically. Furthermore, a binding site in a groove
      of the extracellular domain was proposed but not experimentally verified. In this
      study, we revisited the mechanism of inhibition by diminazene and its binding
      site on ASIC1a, the ASIC subunit with the greatest importance in the central
      nervous system. We show that diminazene slowly blocks ASIC1a, leading to the
      apparent acceleration of desensitization and underestimating its potency; we show
      that diminazene indeed has a submicromolar potency at ASIC1a (IC50 0.3 MUM).
      Moreover, we show that the inhibition is voltage-dependent and competes with that
      by amiloride, a pore blocker of ASICs. Finally, we identify by molecular docking
      a binding site in the ion pore that we confirm by site-directed mutagenesis. In
      summary, our results show that diminazene blocks ASIC1a by a slow open-channel
      block and suggest that diminazene is an interesting lead compound for high
      affinity blockers of ASICs.

PMID- 29025968
TI  - Activation of AMPK/mTORC1-Mediated Autophagy by Metformin Reverses Clk1
      Deficiency-Sensitized Dopaminergic Neuronal Death.
AB  - The autophagy-lysosome pathway (ALP) plays a critical role in the pathology of
      Parkinson's disease (PD). Clk1 (coq7) is a mitochondrial hydroxylase that is
      essential for coenzyme Q (ubiquinone) biosynthesis. We have reported previously
      that Clk1 regulates microglia activation via modulating microglia metabolic
      reprogramming, which contributes to dopaminergic neuronal survival. This study
      explores the direct effect of Clk1 on dopaminergic neuronal survival. We
      demonstrate that Clk1 deficiency inhibited dopaminergic neuronal autophagy in
      cultured MN9D dopaminergic neurons and in the substantia nigra pars compacta of
      Clk+/- mutant mice and consequently sensitized dopaminergic neuron damage and
      behavioral defects. These mechanistic studies indicate that Clk1 regulates the
      AMP-activated protein kinase (AMPK)/rapamycin complex 1 pathway, which in turn
      impairs the ALP and TFEB nuclear translocation. As a result, Clk1 deficiency
      promotes dopaminergic neuronal damage in vivo and in vitro, which ultimately
      contributes to sensitizing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      induced dopaminergic neuronal death and behavioral impairments in Clk1-deficient
      mice. Moreover, we found that activation of autophagy by the AMPK activator
      metformin increases dopaminergic neuronal survival in vitro and in the MPTP
      induced PD model in Clk1 mutant mice. These results reveal that Clk1 plays a
      direct role in dopaminergic neuronal survival via regulating ALPs that may
      contribute to the pathologic development of PD. Modulation of Clk1 activity may
      represent a potential therapeutic target for PD.

PMID- 29025971
TI  - Role of connexin 43 in different forms of intercellular communication - gap
      junctions, extracellular vesicles and tunnelling nanotubes.
AB  - Communication is important to ensure the correct and efficient flow of
      information, which is required to sustain active social networks. A fine-tuned
      communication between cells is vital to maintain the homeostasis and function of
      multicellular or unicellular organisms in a community environment. Although there
      are different levels of complexity, intercellular communication, in prokaryotes
      to mammalians, can occur through secreted molecules (either soluble or
      encapsulated in vesicles), tubular structures connecting close cells or
      intercellular channels that link the cytoplasm of adjacent cells. In mammals,
      these different types of communication serve different purposes, may involve
      distinct factors and are mediated by extracellular vesicles, tunnelling nanotubes
      or gap junctions. Recent studies have shown that connexin 43 (Cx43, also known as
      GJA1), a transmembrane protein initially described as a gap junction protein,
      participates in all these forms of communication; this emphasizes the concept of
      adopting strategies to maximize the potential of available resources by
      reutilizing the same factor in different scenarios. In this Review, we provide an
      overview of the most recent advances regarding the role of Cx43 in intercellular
      communication mediated by extracellular vesicles, tunnelling nanotubes and gap
      junctions.

PMID- 29025972
TI  - 30 years on from the molecular cloning of interferon-tau.

PMID- 29025969
TI  - A versatile optical tool for studying synaptic GABAA receptor trafficking.
AB  - Live-cell imaging methods can provide critical real-time receptor trafficking
      measurements. Here, we describe an optical tool to study synaptic gamma
      aminobutyric acid (GABA) type A receptor (GABAAR) dynamics through adaptable
      fluorescent-tracking capabilities. A fluorogen-activating peptide (FAP) was
      genetically inserted into a GABAAR gamma2 subunit tagged with pH-sensitive green
      fluorescent protein (gamma2pHFAP). The FAP selectively binds and activates
      Malachite Green (MG) dyes that are otherwise non-fluorescent in solution.
      gamma2pHFAP GABAARs are expressed at the cell surface in transfected cortical
      neurons, form synaptic clusters and do not perturb neuronal development.
      Electrophysiological studies show gamma2pHFAP GABAARs respond to GABA and exhibit
      positive modulation upon stimulation with the benzodiazepine diazepam. Imaging
      studies using gamma2pHFAP-transfected neurons and MG dyes show time-dependent
      receptor accumulation into intracellular vesicles, revealing constitutive
      endosomal and lysosomal trafficking. Simultaneous analysis of synaptic, surface
      and lysosomal receptors using the gamma2pHFAP-MG dye approach reveals enhanced
      GABAAR turnover following a bicucculine-induced seizure paradigm, a finding not
      detected by standard surface receptor measurements. To our knowledge, this is the
      first application of the FAP-MG dye system in neurons, demonstrating the
      versatility to study nearly all phases of GABAAR trafficking.

PMID- 29025970
TI  - The Arf GEF GBF1 and Arf4 synergize with the sensory receptor cargo, rhodopsin,
      to regulate ciliary membrane trafficking.
AB  - The small GTPase Arf4 and the Arf GTPase-activating protein (GAP) ASAP1
      cooperatively sequester sensory receptor cargo into transport carriers targeted
      to primary cilia, but the input that drives Arf4 activation in this process
      remains unknown. Here, we show, by using frog retinas and recombinant human
      proteins, that during the carrier biogenesis from the photoreceptor Golgi/trans
      Golgi network (TGN) a functional complex is formed between Arf4, the Arf guanine
      nucleotide exchange factor (GEF) GBF1 and the light-sensing receptor, rhodopsin.
      Rhodopsin and Arf4 bind the regulatory N-terminal dimerization and cyclophillin
      binding (DCB)-homology upstream of Sec7 (HUS) domain of GBF1. The complex is
      sensitive to Golgicide A (GCA), a selective inhibitor of GBF1 that accordingly
      blocks rhodopsin delivery to the cilia, without disrupting the photoreceptor
      Golgi. The emergence of newly synthesized rhodopsin in the endomembrane system is
      essential for GBF1-Arf4 complex formation in vivo Notably, GBF1 interacts with
      the Arf GAP ASAP1 in a GCA-resistant manner. Our findings indicate that
      converging signals on GBF1 from the influx of cargo into the Golgi/TGN and the
      feedback from Arf4, combined with input from ASAP1, control Arf4 activation
      during sensory membrane trafficking to primary cilia.

PMID- 29025974
TI  - Lipid-based DNA/siRNA transfection agents disrupt neuronal bioenergetics and
      mitophagy.
AB  - A multitude of natural and artificial compounds have been recognized to modulate
      autophagy, providing direct or, through associated pathways, indirect entry
      points to activation and inhibition. While these pharmacological tools are
      extremely useful in the study of autophagy, their abundance also suggests the
      potential presence of unidentified autophagic modulators that may interfere with
      experimental designs if applied unknowingly. Here, we report unanticipated
      effects on autophagy and bioenergetics in neuronal progenitor cells (NPCs)
      incubated with the widely used lipid-based transfection reagent lipofectamine
      (LF), which induced mitochondria depolarization followed by disruption of
      electron transport. When NPCs were exposed to LF for 5 h followed by 24, 48, and
      72 h in LF-free media, an immediate increase in mitochondrial ROS production and
      nitrotyrosine formation was observed. These events were accompanied by disrupted
      mitophagy (accumulation of dysfunctional and damaged mitochondria, and of LC3II
      and p62), in an mTOR- and AMPK-independent manner, and despite the increased
      mitochondrial PINK1 (PTEN-inducible kinase 1) localization. Evidence supported a
      role for a p53-mediated abrogation of parkin translocation and/or abrogation of
      membrane fusion between autophagosome and lysosomes. While most of the outcomes
      were LF-specific, only two were shared by OptiMEM exposure (with no serum and
      reduced glucose levels) albeit at lower extents. Taken together, our findings
      show that the use of transfection reagents requires critical evaluation with
      respect to consequences for overall cellular health, particularly in experiments
      designed to address autophagy-inducing effects and/or energy stress.

PMID- 29025973
TI  - Dynamic multi-site phosphorylation by Fyn and Abl drives the interaction between
      CRKL and the novel scaffolding receptors DCBLD1 and DCBLD2.
AB  - Discoidin, CUB, and LCCL domain containing 2 (DCBLD2) is a neuropilin-like
      transmembrane scaffolding receptor with known and anticipated roles in vascular
      remodeling and neuronal positioning. DCBLD2 is also up-regulated in several
      cancers and can drive glioblastomas downstream of activated epidermal growth
      factor receptor. While a few studies have shown either a positive or negative
      role for DCBLD2 in regulating growth factor receptor signaling, little is known
      about the conserved signaling features of DCBLD family members that drive their
      molecular activities. We previously identified DCBLD2 tyrosine phosphorylation
      sites in intracellular YxxP motifs that are required for the phosphorylation
      dependent binding of the signaling adaptors CRK and CRKL (CT10 regulator of
      kinase and CRK-like). These intracellular YxxP motifs are highly conserved across
      vertebrates and between DCBLD family members. Here, we demonstrate that, as for
      DCBLD2, DCBLD1 YxxP motifs are required for CRKL-SH2 (Src homology 2) binding. We
      report that Src family kinases (SFKs) and Abl differentially promote the
      interaction between the CRKL-SH2 domain and DCBLD1 and DCBLD2, and while SFKs and
      Abl each promote DCBLD1 and DCBLD2 binding to the CRKL-SH2 domain, the effect of
      Abl is more pronounced for DCBLD1. Using high-performance liquid chromatography
      coupled with tandem mass spectrometry, we quantified phosphorylation at several
      YxxP sites in DCBLD1 and DCBLD2, mapping site-specific preferences for SFKs and
      Abl. Together, these data provide a platform to decipher the signaling mechanisms
      by which these novel receptors drive their biological activities.

PMID- 29025975
TI  - Recognition of hyperacetylated N-terminus of H2AZ by TbBDF2 from Trypanosoma
      brucei.
AB  - Histone modification plays an important role in various biological processes,
      including gene expression regulation. Bromodomain, as one of histone readers,
      recognizes specifically the epsilon-N-lysine acetylation (KAc) of histone.
      Although the bromodomains and histone acetylation sites of Trypanosoma brucei (T.
      brucei), a lethal parasite responsible for sleeping sickness in human and nagana
      in cattle, have been identified, how acetylated histones are recognized by
      bromodomains is still unknown. Here, the bromodomain factor 2 (TbBDF2) from T.
      brucei was identified to be located in the nucleolus and bind to the
      hyperacetylated N-terminus of H2AZ which dimerizes with H2BV. The bromodomain of
      TbBDF2 (TbBDF2-BD) displays a conserved fold that comprises a left-handed bundle
      of four alpha-helices (alphaZ, alphaA, alphaB, alphaC), linked by loop regions of
      variable length (ZA and BC loops), which form the KAc-binding pocket. NMR
      chemical shift perturbation further revealed that TbBDF2-BD binds to the
      hyperacetylated N-terminus of H2AZ through its KAc-binding pocket. By structure
      based virtual screening combining with the ITC experiment, a small molecule
      compound, GSK2801, was shown to have high affinity to TbBDF2-BD. GSK2801 and the
      hyperacetylated N-terminus of H2AZ have similar binding sites on TbBDF2-BD. In
      addition, GSK2801 competitively inhibits the hyperacetylated N-terminus of H2AZ
      binding to TbBDF2-BD. After treatment of GSK2801, cell growth was inhibited and
      localization of TbBDF2 was disrupted. Our results report a novel bromodomain
      histone recognition by TbBDF2-BD and imply that TbBDF2 may serve as a potential
      chemotherapeutic target for the treatment of trypanosomiasis.

PMID- 29025977
TI  - An Approach to Discovering Novel Muscarinic M1 Receptor Positive Allosteric
      Modulators with Potent Cognitive Improvement and Minimized Gastrointestinal
      Dysfunction.
AB  - Activation of muscarinic M1 receptor (M1R) is a promising approach for improving
      cognitive impairment in Alzheimer's disease. However, an M1R-selective positive
      allosteric modulator (PAM), benzyl quinolone carboxylic acid (BQCA), at 30 mg/kg,
      induced diarrhea in wild-type mice, but not in M1R knockout mice. Moreover, BQCA
      (0.1-1000 nM) augmented electric field stimulation (EFS)-induced ileum
      contraction in an in vitro Magnus assay. Thus, we decided to establish a drug
      screening strategy to discover novel M1 PAMs producing potent cognitive
      improvement with minimized gastrointestinal (GI) dysfunction. We assessed PAM
      parameters of various M1 PAMs with >=100-fold selectivity over other muscarinic
      receptor subtypes by using in vitro binding and functional analysis. Evaluation
      of these M1 PAMs in the Magnus assay revealed a significant correlation between
      percentage of ileum contractions at 1 MUM and their alpha-value, a PAM parameter
      associated with the binding cooperativity between acetylcholine and M1 PAM. M1
      PAMs with lower alpha-value showed lower impact on EFS-induced ileum contraction.
      Next, we characterized in vivo profiles of two M1 PAMs: compound A (log alpha =
      1.18) and compound B (log alpha = 3.30). Compound A, at 30 mg/kg, significantly
      improved scopolamine-induced cognitive deficits without prominent signs of
      diarrhea at up to 1000 mg/kg in mice. In contrast, compound B, at 10 mg/kg,
      showed both significant improvement of scopolamine-induced cognitive deficits and
      severe diarrhea. Thus, fine adjustment of the alpha-values could be a key to
      discovering M1 PAMs yielding potent cognitive improvement with a lower risk of GI
      effects.

PMID- 29025976
TI  - OleA Glu117 is key to condensation of two fatty-acyl coenzyme A substrates in
      long-chain olefin biosynthesis.
AB  - In the interest of decreasing dependence on fossil fuels, microbial hydrocarbon
      biosynthesis pathways are being studied for renewable, tailored production of
      specialty chemicals and biofuels. One candidate is long-chain olefin
      biosynthesis, a widespread bacterial pathway that produces waxy hydrocarbons.
      Found in three- and four-gene clusters, oleABCD encodes the enzymes necessary to
      produce cis-olefins that differ by alkyl chain length, degree of unsaturation,
      and alkyl chain branching. The first enzyme in the pathway, OleA, catalyzes the
      Claisen condensation of two fatty acyl-coenzyme A (CoA) molecules to form a beta
      keto acid. In this report, the mechanistic role of Xanthomonas campestris OleA
      Glu117 is investigated through mutant enzymes. Crystal structures were determined
      for each mutant as well as their complex with the inhibitor cerulenin.
      Complemented by substrate modeling, these structures suggest that Glu117 aids in
      substrate positioning for productive carbon-carbon bond formation. Analysis of
      acyl-CoA substrate hydrolysis shows diminished activity in all mutants. When the
      active site lacks an acidic residue in the 117 position, OleA cannot form
      condensed product, demonstrating that Glu117 has a critical role upstream of the
      essential condensation reaction. Profiling of pH dependence shows that the
      apparent pKa for Glu117 is affected by mutagenesis. Taken together, we propose
      that Glu117 is the general base needed to prime condensation via deprotonation of
      the second, non-covalently bound substrate during turnover. This is the first
      example of a member of the thiolase superfamily of condensing enzymes to contain
      an active site base originating from the second monomer of the dimer.

PMID- 29025980
TI  - Appropriate Use Criteria for 18F-FDG PET/CT in Restaging and Treatment Response
      Assessment of Malignant Disease.

PMID- 29025978
TI  - The Anti-Vascular Endothelial Growth Factor Receptor-1 Monoclonal Antibody D16F7
      Inhibits Glioma Growth and Angiogenesis In Vivo.
AB  - The vascular endothelial growth factor (VEGF) receptor-1 (VEGFR-1) is a tyrosine
      kinase receptor that does not play a relevant role in physiologic angiogenesis in
      adults, whereas it is important in tumor angiogenesis. In high-grade glioma VEGFR
      1 expression by tumor endothelium and neoplastic cells contributes to the
      aggressive phenotype. We recently generated an anti-VEGFR-1 monoclonal antibody
      (D16F7 mAb) characterized by a novel mechanism of action, since it hampers
      receptor activation without interfering with ligand binding. The mAb is able to
      inhibit chemotaxis and extracellular matrix invasion of glioma cells in vitro
      stimulated by VEGF-A and by the VEGFR-1-selective ligand placental growth factor
      (PlGF). In this study, we have investigated the influence of D16F7 on glioma
      growth and angiogenesis in vivo using C6 glioma cells transfected with the human
      VEGFR-1. D16F7 was able to inhibit receptor activation and migration and
      extracellular matrix invasion of C6 cells overexpressing the receptor in response
      to PlGF and VEGF-A. In nude mice, treatment with 10 and 20 mg/kg D16F7 as a
      single agent was well tolerated and significantly inhibited glioma growth (P <
      0.001). Strikingly, in an intracranial orthotopic model, mice dosed with 20 mg/kg
      D16F7 demonstrated a 65% increase in median survival time compared with vehicle
      treated controls (P < 0.001) with a high percentage of long-term survivors (46%).
      These effects were associated with glioma cell apoptosis and decreased tumor
      associated vessel formation. Overall, these results highlight the therapeutic
      potential of D16F7 in glioma treatment, deserving further investigation after a
      humanization process as single agent or in combination therapies.

PMID- 29025979
TI  - Melatonin Receptor Agonist Piromelatine Ameliorates Impaired Glucose Metabolism
      in Chronically Stressed Rats Fed a High-Fat Diet.
AB  - Modern lifestyle factors (high-caloric food rich in fat) and daily chronic stress
      are important risk factors for metabolic disturbances. Increased hypothalamic
      pituitary-adrenal (HPA) axis activity and the subsequent excess production of
      glucocorticoids (GCs) in response to chronic stress (CS) leads to increases in
      metabolic complications, such as type 2 diabetes and insulin resistance (IR).
      Melatonin (MLT), which protects several regulatory components of the HPA axis
      from GC-induced deterioration, might improve glucose homeostasis. Piromelatine is
      a melatonin receptor-1/melatonin receptor-2 (MT1/MT2) agonist with high affinity
      for MLT receptors and a longer duration of action than MLT. The objective of the
      present study was to explore the potential effects of piromelatine on glucose and
      lipid metabolism and insulin sensitivity in rats with IR induced by a high-fat
      diet combined with CS (CF). The results showed that piromelatine prevented the
      suppression of body weight gain and energy intake induced by CF and normalized CF
      induced hyperglycemia and homeostasis model assessment-IR index, which suggests
      that piromelatine prevented whole-body IR. Piromelatine also prevented CF-induced
      dysregulation of genes involved in glucose and lipid metabolism, including
      proinflammatory cytokines, in adipose tissue. In addition, piromelatine also
      attenuated CF-induced excess free corticosterone release, increased
      glucocorticoid receptor expression, and decreased 11beta-hydroxysteroid
      dehydrogenase-1 expression, suggesting that piromelatine might ameliorate
      impaired glucose metabolism and prevent IR by normalizing HPA-axis functions. In
      conclusion, piromelatine might be a novel therapeutic agent for glucose
      intolerance and IR.

PMID- 29025981
TI  - How Should the FDA Review Diagnostic Radiopharmaceuticals?
AB  - The purpose of this article is to reconsider the manner in which the U.S. Food
      and Drug Administration (FDA) reviews diagnostic radiopharmaceuticals. Mass
      characteristics of several common nonradioactive drugs and several diagnostic
      radiopharmaceuticals are considered. A history of the regulation of
      radiopharmaceuticals is presented. The Society of Nuclear Medicine and Molecular
      Imaging and the American College of Nuclear Medicine should choose the membership
      of a radiopharmaceutical advisory committee, and the FDA should contract with
      them to do so. Members of the radiopharmaceutical advisory committee should
      decide on the data to be presented by the manufacturer or the compounder and
      review those data, and the FDA should honor their decision. In this way,
      requirements would be radiopharmaceutical-specific, and much information of
      questionable usefulness would be foregone.

PMID- 29025982
TI  - Appropriate Use Criteria for Somatostatin Receptor PET Imaging in Neuroendocrine
      Tumors.

PMID- 29025983
TI  - Predictive Value of 18F-FDG PET in Patients with Advanced Medullary Thyroid
      Carcinoma Treated with Vandetanib.
AB  - Therapeutic options in advanced medullary thyroid carcinoma (MTC) have markedly
      improved since the introduction of tyrosine kinase inhibitors (TKIs). We aimed to
      assess the role of metabolic imaging using 18F-FDG PET/CT shortly before and 3 mo
      after initiation of TKI treatment. Methods: Eighteen patients with advanced and
      progressive MTC scheduled for vandetanib treatment underwent baseline 18F-FDG
      PET/CT before and 3 mo after TKI treatment initiation. During follow-up, CT scans
      were obtained every 3 mo and analyzed according to RECIST. The predictive value
      for estimating progression-free survival (PFS) and overall survival (OS) was
      examined by investigating the 18F-FDG SUVmean/max of the metabolically most
      active lesion, as well as by analyzing clinical parameters (tumor marker doubling
      times [calcitonin, carcinoembryonic antigen], prior therapies, rearranged-during
      transfection mutational status, and disease type). Results: Within a median
      follow-up of 5.2 y, 9 patients experienced disease progression after a median
      interval of 2.1 y, whereas the remainder had ongoing disease control (5 with a
      partial response and 4 with stable disease). Eight of the 9 patients with
      progressive disease died from MTC after a median of 3.5 y after TKI initiation. A
      pretherapeutic SUVmean of more than 4.0 predicted a significantly shorter PFS
      (1.9 y vs. 5.2 y, P = 0.04). Furthermore, sustained high 18F-FDG uptake at 3 mo
      with a SUVmean of more than 2.8 tended to portend an unfavorable prognosis, with
      a PFS of 1.9 y (vs. 3.5 y, P = 0.3). Prolonged carcinoembryonic antigen doubling
      times were significantly correlated with longer PFS (r = 0.7) and OS (r = 0.76, P
      < 0.01). None of the other clinical parameters had prognostic significance.
      Conclusion: Pretherapeutic 18F-FDG PET/CT provides prognostic information in
      patients with advanced MTC scheduled for treatment with the TKI vandetanib. A low
      tumor metabolism with an SUVmean of less than 4.0 before treatment predicts a
      longer PFS.

PMID- 29025984
TI  - Synthesis and Biologic Evaluation of a Novel 18F-Labeled Adnectin as a PET
      Radioligand for Imaging PD-L1 Expression.
AB  - The programmed death protein (PD-1) and its ligand (PD-L1) play critical roles in
      a checkpoint pathway cancer cells exploit to evade the immune system. A same-day
      PET imaging agent for measuring PD-L1 status in primary and metastatic lesions
      could be important for optimizing drug therapy. Herein, we have evaluated the
      tumor targeting of an anti-PD-L1 adnectin after 18F-fluorine labeling. Methods:
      An anti-PD-L1 adnectin was labeled with 18F in 2 steps. This synthesis featured
      fluorination of a novel prosthetic group, followed by a copper-free click
      conjugation to a modified adnectin to generate 18F-BMS-986192. 18F-BMS-986192 was
      evaluated in tumors using in vitro autoradiography and PET with mice bearing
      bilateral PD-L1-negative (PD-L1(-)) and PD-L1-positive (PD-L1(+)) subcutaneous
      tumors. 18F-BMS-986192 was evaluated for distribution, binding, and radiation
      dosimetry in a healthy cynomolgus monkey. Results:18F-BMS-986192 bound to human
      and cynomolgus PD-L1 with a dissociation constant of less than 35 pM, as measured
      by surface plasmon resonance. This adnectin was labeled with 18F to yield a PET
      radioligand for assessing PD-L1 expression in vivo. 18F-BMS-986192 bound to tumor
      tissues as a function of PD-L1 expression determined by immunohistochemistry.
      Radioligand binding was blocked in a dose-dependent manner. In vivo PET imaging
      clearly visualized PD-L1 expression in mice implanted with PD-L1(+), L2987
      xenograft tumors. Two hours after dosing, a 3.5-fold-higher uptake (2.41 +/- 0.29
      vs. 0.82 +/- 0.11 percentage injected dose per gram, P < 0.0001) was observed in
      L2987 than in control HT-29 (PD-L1(-)) tumors. Coadministration of 3 mg/kg
      ADX_5322_A02 anti-PD-L1 adnectin reduced tumor uptake at 2 h after injection by
      approximately 70%, whereas HT-29 uptake remained unchanged, demonstrating PD-L1
      specific binding. Biodistribution in a nonhuman primate showed binding in the PD
      L1-rich spleen, with rapid blood clearance through the kidneys and bladder.
      Binding in the PD-L1(+) spleen was reduced by coadministration of BMS-986192.
      Dosimetry estimates indicate that the kidney is the dose-limiting organ, with an
      estimated human absorbed dose of 2.20E-01 mSv/MBq. Conclusion:18F-BMS-986192
      demonstrated the feasibility of noninvasively imaging the PD-L1 status of tumors
      by small-animal PET studies. Clinical studies with 18F-BMS-986192 are under way
      to measure PD-L1 expression in human tumors.

PMID- 29025986
TI  - 18F-FDG-Avid Thyroid Incidentalomas: The Importance of Contextual Interpretation.
AB  - 18F-FDG-avid thyroid incidentaloma (TI) is seen in approximately 2.5% of patients
      imaged for staging or response assessment of malignancy and represents thyroid
      cancer in approximately 35% of cases. Consequently, the 2015 American Thyroid
      Association guidelines strongly recommend investigation of all 18F-FDG-avid
      nodules 1 cm or larger with ultrasound and fine-needle aspiration cytology (FNA).
      This study aimed to assess the overall and thyroid cancer-specific survival in a
      large cohort of patients with 18F-FDG-avid TI with long-term follow-up to assess
      the validity of this approach. Methods: Retrospective review of 45,680 PET/CT
      scans performed at a comprehensive cancer center from January 2007 to January
      2015 identified 2,588 18F-FDG PET/CT reports referring to the thyroid. After
      exclusion of nonavid thyroid nodules, diffuse 18F-FDG uptake, known thyroid
      cancer, abnormalities adjacent to the thyroid, and repeat studies, 500 patients
      (1.1%) with TI were identified, of whom 362 had confirmed death or more than 12
      mo of clinical follow-up. Variables including age, sex, primary malignancy,
      overall survival, thyroid cancer-specific survival, FNA, and histopathology were
      collected until January 2016. Multivariate logistic regression and survival
      analysis were performed. Results: The 362 analyzed patients (65% female) had a
      median age of 65 y (range, 19-96 y) and follow-up of 24 mo (range, 1-103 mo).
      Lymphoid, lung, and colorectal malignancy were the most common staging
      indications. Median overall survival was 20 mo (interquartile range, 9.5-39 mo).
      Most of the 180 observed deaths were due to the primary malignancy under
      investigation (92.2%) or to causes not related to cancer (7.2%); one patient
      (0.6%) died from incidentally detected medullary thyroid cancer. 18F-FDG avidity
      in the index malignancy, an advanced stage for that malignancy, and a clinician
      decision not to investigate 18F-FDG-avid TI were all predictors of mortality,
      with hazard ratios of 8.5, 3.0, and 3.3, respectively, and 95% confidence
      intervals of 4.6-15.8, 2.3-3.9, and 2.0-5.0, respectively (P < 0.001). Of 131
      patients suitable for cytologic or histopathologic evaluation, 47 (36%) had
      incidental thyroid cancer (24 papillary, 11 malignant FNA, 5 oncocytic/Hurthle
      cell, 2 medullary, 1 follicular, and 4 metastases from underlying malignancy).
      Conclusion: Overall survival with 18F-FDG-avid TI was poor because of the
      prognosis associated with underlying malignancy, which must be considered before
      investigation of 18F-FDG-avid TI and certainly before aggressive treatment.
      Active surveillance should be considered in this group of patients.

PMID- 29025985
TI  - Safety, Biodistribution, and Radiation Dosimetry of 68Ga-OPS202 in Patients with
      Gastroenteropancreatic Neuroendocrine Tumors: A Prospective Phase I Imaging
      Study.
AB  - Preclinical and preliminary clinical evidence indicates that radiolabeled
      somatostatin (sst) receptor antagonists perform better than agonists in detecting
      neuroendocrine tumors (NETs). We performed a prospective phase I/II study to
      evaluate the sst receptor antagonist 68Ga-OPS202 (68Ga-NODAGA-JR11; NODAGA =
      1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid and JR11 = Cpa-c(dCys
      Aph(Hor)-dAph(Cbm)-Lys-Thr-Cys)-dTyr-NH2)) for PET imaging. Here, we report the
      results of phase I of the study. Methods: Patients received 2 single 150-MBq
      intravenous injections of 68Ga-OPS202 3-4 wk apart (15 MUg of peptide at visit 1
      and 50 MUg at visit 2). At visit 1, a dynamic PET/CT scan over the kidney was
      obtained during the first 30 min after injection, and static whole-body scans
      were obtained at 0.5, 1, 2, and 4 h after injection; at visit 2, a static whole
      body scan was obtained at 1 h. Blood samples and urine were collected at regular
      intervals to determine 68Ga-OPS202 pharmacokinetics. Safety, biodistribution,
      radiation dosimetry, and the most appropriate imaging time point for 68Ga-OPS202
      were assessed. Results: Twelve patients with well-differentiated
      gastroenteropancreatic (GEP) NETs took part in the study. 68Ga-OPS202 cleared
      rapidly from the blood, with a mean residence time of 2.4 +/- 1.1 min/L. The
      organs with the highest mean dose coefficients were the urinary bladder wall,
      kidneys, and spleen. The calculated effective dose was 2.4E-02 +/- 0.2E-02
      mSv/MBq, corresponding to 3.6 mSv, for a reference activity of 150 MBq. Based on
      total numbers of detected malignant lesions, the optimal time window for the scan
      was between 1 and 2 h. For malignant liver lesions, the time point at which most
      patients had the highest mean tumor contrast was 1 h. 68Ga-OPS202 was well
      tolerated; adverse events were grade 1 or 2, and there were no signals of concern
      from laboratory blood or urinalysis tests. Conclusion:68Ga-OPS202 showed
      favorable biodistribution and imaging properties, with optimal tumor contrast
      between 1 and 2 h after injection. Dosimetry analysis revealed that the dose
      delivered by 68Ga-OPS202 to organs is similar to that delivered by other 68Ga
      labeled sst analogs. Further evaluation of 68Ga-OPS202 for PET/CT imaging of NETs
      is therefore warranted.

PMID- 29025988
TI  - Advanced Methods for Radiolabeling Multimodality Nanomedicines for SPECT/MRI and
      PET/MRI.
AB  - The advent of hybrid cameras that combine MRI with either SPECT or PET has
      stimulated growing interest in developing multimodality imaging probes. Countless
      options are available for fusing magnetically active species with positron- or
      gamma-ray-emitting radionuclides. The initial problem is one of choice: which
      chemical systems are a suitable basis for developing hybrid imaging agents? Any
      attempt to answer this question must also address how the physical, chemical, and
      biologic properties of a unified imaging agent can be tailored to ensure that
      optimum specificity and contrast are achieved simultaneously for both imaging
      modalities. Nanoparticles have emerged as attractive platforms for building
      multimodality radiotracers for SPECT/MRI and PET/MRI. A wide variety of
      nanoparticle constructs have been utilized as radiotracers, but irrespective of
      the particle class, radiolabeling remains a key step. Classic methods for
      radiolabeling nanoparticles involve functionalization of the particle surface,
      core, or coating. These modifications typically rely on using traditional metal
      ion chelate or prosthetic group chemistries. Though seemingly innocuous,
      appending nanoparticles with these radiolabeling handles can have dramatic
      effects on important properties such as particle size, charge, and solubility. In
      turn, alterations in the chemical and physical properties of the nanoparticle
      often have a negative impact on their pharmacologic profile. A central challenge
      in radiolabeling nanoparticles is to identify alternative chemical methods that
      facilitate the introduction of a radioactive nuclide without detrimental effects
      on the pharmacokinetic and toxicologic properties of the construct. Efforts to
      solve this challenge have generated a range of innovative chelate-free
      radiolabeling methods that exploit intrinsic chemical features of nanoparticles.
      Here, the chemistry of 9 mechanistically distinct methods for radiolabeling
      nanoparticles is presented. This discourse illustrates the evolution of
      nanoparticle radiochemistry from classic approaches to modern chelate-free or
      intrinsic methods.

PMID- 29025987
TI  - Preclinical Development of CD38-Targeted [89Zr]Zr-DFO-Daratumumab for Imaging
      Multiple Myeloma.
AB  - Multiple myeloma (MM) is a plasma B-cell hematologic cancer that causes
      significant skeletal morbidity. Despite improvements in survival, heterogeneity
      in response remains a major challenge in MM. Cluster of differentiation 38 (CD38)
      is a type II transmembrane glycoprotein overexpressed in myeloma cells and is
      implicated in MM cell signaling. Daratumumab is a U.S. Food and Drug
      Administration-approved high-affinity monoclonal antibody targeting CD38 that is
      clinically benefiting refractory MM patients. Here, we evaluated [89Zr]Zr
      desferrioxamine (DFO)-daratumumab PET/CT imaging in MM tumor models. Methods:
      Daratumumab was conjugated to DFO-p-benzyl-isothiocyanate (DFO-Bz-NCS) for
      radiolabeling with 89Zr. Chelator conjugation was confirmed by electrospray
      ionization-mass spectrometry, and radiolabeling was monitored by instant thin
      layer chromatography. Daratumumab was conjugated to Cyanine5 (Cy5) dye for cell
      microscopy. In vitro and in vivo evaluation of [89Zr]Zr-DFO-daratumumab was
      performed using CD38+ human myeloma MM1.S-luciferase (MM1.S) cells. Cellular
      studies determined the affinity, immunoreactivity, and specificity of [89Zr]Zr
      DFO-daratumumab. A 5TGM1-luciferase (5TGM1)/KaLwRij MM mouse model served as
      control for imaging background noise. [89Zr]Zr-DFO-daratumumab PET/CT small
      animal imaging was performed in severe combined immunodeficient mice bearing
      solid and disseminated MM tumors. Tissue biodistribution (7 d after tracer
      administration, 1.11 MBq/animal, n = 4-6/group) was performed in wild-type and
      MM1.S tumor-bearing mice. Results: A specific activity of 55.5 MBq/nmol (0.37
      MBq/MUg) was reproducibly obtained with [89Zr]Zr-daratumumab-DFO. Flow cytometry
      confirmed CD38 expression (>99%) on the surface of MM1.S cells. Confocal
      microscopy with daratumumab-Cy5 demonstrated specific cell binding. Dissociation
      constant, 3.3 nM (+/-0.58), and receptor density, 10.1 fmol/mg (+/-0.64), was
      obtained with a saturation binding assay. [89Zr]Zr-DFO-daratumumab/PET
      demonstrated specificity and sensitivity for detecting CD38+ myeloma tumors of
      variable sizes (8.5-128 mm3) with standardized uptake values ranging from 2.1 to
      9.3. Discrete medullar lesions, confirmed by bioluminescence images, were
      efficiently imaged with [89Zr]Zr-DFO-daratumumab/PET. Biodistribution at 7 d
      after administration of [89Zr]Zr-DFO-daratumumab showed prominent tumor uptake
      (27.7 +/- 7.6 percentage injected dose per gram). In vivo blocking was achieved
      with a 200-fold excess of unlabeled daratumumab. Conclusion: [89Zr]Zr-DFO- and
      Cy5-daratumumab demonstrated superb binding to CD38+ human MM cells and
      significantly low binding to CD38low cells. Daratumumab bioconjugates are being
      evaluated for image-guided delivery of therapeutic radionuclides.

PMID- 29025989
TI  - Low-Level Endogenous PSMA Expression in Nonprostatic Tumor Xenografts Is
      Sufficient for In Vivo Tumor Targeting and Imaging.
AB  - Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer
      and within the neovasculature of other solid tumors. The nonprostatic expression
      of PSMA has been reported exclusively within the neovasculature endothelial cells
      of nonprostatic cancers; however, there are few reports on PSMA expression in
      epithelial cells. Herein, we describe PSMA expression in nonprostatic epithelial
      cells and characterize the potential of PSMA-binding agents to noninvasively
      detect that expression. Methods: PSMA expression data were extracted from
      publicly available genomic databases. Genomic data were experimentally validated
      for PSMA expression-by quantitative reverse transcription polymerase chain
      reaction, flow cytometry, and Western blotting-in several nonprostatic cell lines
      and xenografts of melanoma and small cell lung cancer (SCLC) origin. The
      feasibility of PSMA detection in those tumor models was further established using
      PSMA-based nuclear and optical imaging agents and by biodistribution, blocking,
      and ex vivo molecular characterization studies. Results: We discovered that a
      small percentage of nonprostatic cancer cell lines and tumors express PSMA.
      Importantly, PSMA expression was sufficiently high to image established melanoma
      and SCLC xenografts using PSMA-based nuclear and optical imaging agents.
      Conclusion: These results indicate that PSMA expression in nonprostatic tumors
      may not be limited to the endothelium but may also include solid tumor tissue of
      nonprostatic cancers including melanoma and SCLC. Our observations indicate
      broader applicability of PSMA-targeted imaging and therapeutics.

PMID- 29025990
TI  - 177Lu-3BP-227 for Neurotensin Receptor 1-Targeted Therapy of Metastatic
      Pancreatic Adenocarcinoma: First Clinical Results.
AB  - Neurotensin receptor 1 (NTR1) is overexpressed in ductal pancreatic
      adenocarcinoma, which is still one of the deadliest cancers, with a very poor
      prognosis. Eligible patients were offered salvage radiopharmaceutical therapy
      with the novel NTR1 antagonist 177Lu-3BP-227. Methods: Six patients with
      confirmed ductal pancreatic adenocarcinoma who had exhausted all other treatment
      options received 177Lu-3BP-227 for evaluation of NTR1 expression in vivo. Three
      patients received treatment activities of 5.1-7.5 GBq. Results: Administration of
      177Lu-3BP-227 was well tolerated by all patients. The kidneys were identified as
      the dose-limiting organ. The most severe adverse event was reversible grade 2
      anemia. One patient achieved a partial response and experienced significant
      improvement of symptoms and quality of life. This patient survived 13 mo from
      diagnosis and 11 mo from the start of 177Lu-3BP-227 therapy. Conclusion: This
      initial report provides clinical evidence of the feasibility of treatment of
      ductal pancreatic adenocarcinoma using 177Lu-3BP-227.

PMID- 29025992
TI  - Nonreciprocal lasing in topological cavities of arbitrary geometries.
AB  - Resonant cavities are essential building blocks governing many wave-based
      phenomena, but their geometry and reciprocity fundamentally limit the integration
      of optical devices. We report, at telecommunication wavelengths, geometry
      independent and integrated nonreciprocal topological cavities that couple
      stimulated emission from one-way photonic edge states to a selected waveguide
      output with an isolation ratio in excess of 10 decibels. Nonreciprocity
      originates from unidirectional edge states at the boundary between photonic
      structures with distinct topological invariants. Our experimental demonstration
      of lasing from topological cavities provides the opportunity to develop complex
      topological circuitry of arbitrary geometries for the integrated and robust
      generation and transport of photons in classical and quantum regimes.

PMID- 29025991
TI  - Crystal structure of a TAPBPR-MHC I complex reveals the mechanism of peptide
      editing in antigen presentation.
AB  - Central to CD8+ T cell-mediated immunity is the recognition of peptide-major
      histocompatibility complex class I (p-MHC I) proteins displayed by antigen
      presenting cells. Chaperone-mediated loading of high-affinity peptides onto MHC I
      is a key step in the MHC I antigen presentation pathway. However, the structure
      of MHC I with a chaperone that facilitates peptide loading has not been
      determined. We report the crystal structure of MHC I in complex with the peptide
      editor TAPBPR (TAP-binding protein-related), a tapasin homolog. TAPBPR remodels
      the peptide-binding groove of MHC I, resulting in the release of low-affinity
      peptide. Changes include groove relaxation, modifications of key binding pockets,
      and domain adjustments. This structure captures a peptide-receptive state of MHC
      I and provides insights into the mechanism of peptide editing by TAPBPR and, by
      analogy, tapasin.

PMID- 29025993
TI  - A cryofuge for cold-collision experiments with slow polar molecules.
AB  - Ultracold molecules represent a fascinating research frontier in physics and
      chemistry, but it has proven challenging to prepare dense samples at low
      velocities. Here, we present a solution to this goal by means of a
      nonconventional approach dubbed cryofuge. It uses centrifugal force to bring
      cryogenically cooled molecules to kinetic energies below 1 K * kB in the
      laboratory frame, where kB is the Boltzmann constant, with corresponding fluxes
      exceeding 1010 per second at velocities below 20 meters per second. By attaining
      densities higher than 109 per cubic centimeter and interaction times longer than
      25 milliseconds in samples of fluoromethane as well as deuterated ammonia, we
      observed cold dipolar collisions between molecules and determined their collision
      cross sections.

PMID- 29025996
TI  - Structure of the TAPBPR-MHC I complex defines the mechanism of peptide loading
      and editing.
AB  - Adaptive immunity is shaped by a selection of peptides presented on major
      histocompatibility complex class I (MHC I) molecules. The chaperones Tapasin
      (Tsn) and TAP-binding protein-related (TAPBPR) facilitate MHC I peptide loading
      and high-affinity epitope selection. Despite the pivotal role of Tsn and TAPBPR
      in controlling the hierarchical immune response, their catalytic mechanism
      remains unknown. Here, we present the x-ray structure of the TAPBPR-MHC I
      complex, which delineates the central step of catalysis. TAPBPR functions as
      peptide selector by remodeling the MHC I alpha2-1-helix region, stabilizing the
      empty binding groove, and inserting a loop into the groove that interferes with
      peptide binding. The complex explains how mutations in MHC I-specific chaperones
      cause defects in antigen processing and suggests a unifying mechanism of peptide
      proofreading.

PMID- 29025997
TI  - Distinguishing a Majorana zero mode using spin-resolved measurements.
AB  - One-dimensional topological superconductors host Majorana zero modes (MZMs), the
      nonlocal property of which could be exploited for quantum computing applications.
      We use spin-polarized scanning tunneling microscopy to show that MZMs realized in
      self-assembled Fe chains on the surface of Pb have a spin polarization that
      exceeds that stemming from the magnetism of these chains. This feature, captured
      by our model calculations, is a direct consequence of the nonlocality of the
      Hilbert space of MZMs emerging from a topological band structure. Our study
      establishes spin-polarization measurements as a diagnostic tool to distinguish
      topological MZMs from trivial in-gap states of a superconductor.

PMID- 29025995
TI  - Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer
      biomass.
AB  - Ammonia is a ubiquitous by-product of cellular metabolism; however, the
      biological consequences of ammonia production are not fully understood,
      especially in cancer. We found that ammonia is not merely a toxic waste product
      but is recycled into central amino acid metabolism to maximize nitrogen
      utilization. In our experiments, human breast cancer cells primarily assimilated
      ammonia through reductive amination catalyzed by glutamate dehydrogenase (GDH);
      secondary reactions enabled other amino acids, such as proline and aspartate, to
      directly acquire this nitrogen. Metabolic recycling of ammonia accelerated
      proliferation of breast cancer. In mice, ammonia accumulated in the tumor
      microenvironment and was used directly to generate amino acids through GDH
      activity. These data show that ammonia is not only a secreted waste product but
      also a fundamental nitrogen source that can support tumor biomass.

PMID- 29025998
TI  - You "Like" Us!

PMID- 29026000
TI  - Package size matters: tobacco packaging, retail merchandising and its influence
      on trial and impulse sales.

PMID- 29025999
TI  - Marijuana as a 'concept' flavour for cigar products: availability and price near
      California schools.
AB  - OBJECTIVES: To assess the retail availability of cigar products that refer to
      marijuana and the largest package size of cigarillos available for <=$1. METHODS:
      Trained data collectors conducted marketing surveillance in a random sample of
      licensed tobacco retailers that sold little cigars/cigarillos (LCCs) (n=530) near
      a statewide sample of middle and high schools (n=132) in California. Multilevel
      models examined the presence of marijuana co-marketing and cigarillo pack size as
      a function of school/neighbourhood characteristics and adjusted for store type.
      RESULTS: Of stores that sold LCCs, approximately 62% contained at least one form
      of marijuana co-marketing: 53.2% sold cigar wraps marketed as blunt wraps, 27.2%
      sold cigarillos marketed as blunts and 26.0% sold at least one LCC with a
      marijuana-related 'concept' flavour. Controlling for store type, marijuana co
      marketing was more prevalent in school neighbourhoods with a higher proportion of
      young residents (ages 5-17 years) and with lower median household income. Nearly
      all stores that sold LCCs (87.9%) offered the products for <=$1. However,
      significantly larger packs at similarly low prices were available near schools in
      lower-income neighbourhoods and with a lower percentage of Hispanic students.
      CONCLUSIONS: Understanding how the tobacco industry manipulates cigar products
      and marketing to capitalise on the appeal of marijuana to youth and other
      priority populations is important to inform regulation, particularly for
      flavoured tobacco products. In addition, the retail availability of five and six
      packs of LCCs for <=$1 near California schools underscores policy recommendations
      to establish minimum prices for multipacks.

PMID- 29026001
TI  - Understanding a role for hypoxia in lesion formation and location in the deep and
      periventricular white matter in small vessel disease and multiple sclerosis.
AB  - The deep and periventricular white matter is preferentially affected in several
      neurological disorders, including cerebral small vessel disease (SVD) and
      multiple sclerosis (MS), suggesting that common pathogenic mechanisms may be
      involved in this injury. Here we consider the potential pathogenic role of tissue
      hypoxia in lesion development, arising partly from the vascular anatomy of the
      affected white matter. Specifically, these regions are supplied by a sparse
      vasculature fed by long, narrow end arteries/arterioles that are vulnerable to
      oxygen desaturation if perfusion is reduced (as in SVD, MS and diabetes) or if
      the surrounding tissue is hypoxic (as in MS, at least). The oxygen crisis is
      exacerbated by a local preponderance of veins, as these can become highly
      desaturated 'sinks' for oxygen that deplete it from surrounding tissues.
      Additional haemodynamic deficiencies, including sluggish flow and impaired
      vasomotor reactivity and vessel compliance, further exacerbate oxygen
      insufficiency. The cells most vulnerable to hypoxic damage, including
      oligodendrocytes, die first, resulting in demyelination. Indeed, in preclinical
      models, demyelination is prevented if adequate oxygenation is maintained by
      raising inspired oxygen concentrations. In agreement with this interpretation,
      there is a predilection of lesions for the anterior and occipital horns of the
      lateral ventricles, namely regions located at arterial watersheds, or border
      zones, known to be especially susceptible to hypoperfusion and hypoxia. Finally,
      mitochondrial dysfunction due to genetic causes, as occurs in leucodystrophies or
      due to free radical damage, as occurs in MS, will compound any energy
      insufficiency resulting from hypoxia. Viewing lesion formation from the
      standpoint of tissue oxygenation not only reveals that lesion distribution is
      partly predictable, but may also inform new therapeutic strategies.

PMID- 29025994
TI  - Loci associated with skin pigmentation identified in African populations.
AB  - Despite the wide range of skin pigmentation in humans, little is known about its
      genetic basis in global populations. Examining ethnically diverse African
      genomes, we identify variants in or near SLC24A5, MFSD12, DDB1, TMEM138, OCA2,
      and HERC2 that are significantly associated with skin pigmentation. Genetic
      evidence indicates that the light pigmentation variant at SLC24A5 was introduced
      into East Africa by gene flow from non-Africans. At all other loci, variants
      associated with dark pigmentation in Africans are identical by descent in South
      Asian and Australo-Melanesian populations. Functional analyses indicate that
      MFSD12 encodes a lysosomal protein that affects melanogenesis in zebrafish and
      mice, and that mutations in melanocyte-specific regulatory regions near
      DDB1/TMEM138 correlate with expression of ultraviolet response genes under
      selection in Eurasians.

PMID- 29026002
TI  - Risk of bias reporting in the recent animal focal cerebral ischaemia literature.
AB  - BACKGROUND: Findings from in vivo research may be less reliable where studies do
      not report measures to reduce risks of bias. The experimental stroke community
      has been at the forefront of implementing changes to improve reporting, but it is
      not known whether these efforts are associated with continuous improvements. Our
      aims here were firstly to validate an automated tool to assess risks of bias in
      published works, and secondly to assess the reporting of measures taken to reduce
      the risk of bias within recent literature for two experimental models of stroke.
      METHODS: We developed and used text analytic approaches to automatically
      ascertain reporting of measures to reduce risk of bias from full-text articles
      describing animal experiments inducing middle cerebral artery occlusion (MCAO) or
      modelling lacunar stroke. RESULTS: Compared with previous assessments, there were
      improvements in the reporting of measures taken to reduce risks of bias in the
      MCAO literature but not in the lacunar stroke literature. Accuracy of automated
      annotation of risk of bias in the MCAO literature was 86% (randomization), 94%
      (blinding) and 100% (sample size calculation); and in the lacunar stroke
      literature accuracy was 67% (randomization), 91% (blinding) and 96% (sample size
      calculation). DISCUSSION: There remains substantial opportunity for improvement
      in the reporting of animal research modelling stroke, particularly in the lacunar
      stroke literature. Further, automated tools perform sufficiently well to identify
      whether studies report blinded assessment of outcome, but improvements are
      required in the tools to ascertain whether randomization and a sample size
      calculation were reported.

PMID- 29026003
TI  - Neutralization of either IL-17A or IL-17F is sufficient to inhibit house dust
      mite induced allergic asthma in mice.
AB  - T helper (Th)17 immune response participates in allergic lung inflammation and
      asthma is reduced in the absence of interleukin (IL)-17 in mice. Since IL-17A and
      IL-17F are induced and bind the shared receptor IL-17RA, we asked whether both IL
      17A and IL-17F contribute to house dust mite (HDM) induced asthma. We report that
      allergic lung inflammation is attenuated in absence of either IL-17A or IL-17F
      with reduced airway hyperreactivity, eosinophilic inflammation, goblet cell
      hyperplasia, cytokine and chemokine production as found in absence of IL-17RA.
      Furthermore, specific antibody neutralization of either IL-17A or IL-17F given
      during the sensitization phase attenuated allergic lung inflammation and airway
      hyperreactivity. In vitro activation by HDM of primary dendritic cells revealed a
      comparable induction of CXCL1 and IL-6 expression and the response to IL-17A and
      IL-17F relied on IL-17RA signaling via the adaptor protein act1 in fibroblasts.
      Therefore, HDM-induced allergic respiratory response depends on IL-17RA via act1
      signaling and inactivation of either IL-17A or IL-17F is sufficient to attenuate
      allergic asthma in mice.

PMID- 29026004
TI  - Oxidative stress regulates cellular bioenergetics in esophageal squamous cell
      carcinoma cell.
AB  - The aim of the present study was to explore the effects of oxidative stress
      induced by CoCl2 and H2O2 on the regulation of bioenergetics of esophageal
      squamous cell carcinoma (ESCC) cell line TE-1 and analyze its underlying
      mechanism. Western blot results showed that CoCl2 and H2O2 treatment of TE-1
      cells led to significant reduction in mitochondrial respiratory chain complex
      subunits expression and increasing intracellular reactive oxygen species (ROS)
      production. We further found that TE-1 cells treated with CoCl2, a hypoxia
      mimicking reagent, dramatically reduced the oxygen consumption rate (OCR) and
      increased the extracellular acidification rate (ECAR). However, H2O2 treatment
      decreased both the mitochondrial respiration and aerobic glycolysis
      significantly. Moreover, we found that H2O2 induces apoptosis in TE-1 cells
      through the activation of PARP, Caspase 3, and Caspase 9. Therefore, our findings
      indicate that CoCl2 and H2O2 could cause mitochondrial dysfunction by up
      regulation of ROS and regulating the cellular bioenergy metabolism, thus
      affecting the survival of tumor cells.

PMID- 29026005
TI  - Low expression of miR-30a-5p induced the proliferation and invasion of oral
      cancer via promoting the expression of FAP.
AB  - The study aimed at investigating the effects of miR-30a-5p on the biological
      functions of oral cancer cells and figuring out the potential mechanism. We first
      verified the low expression of miR-30a-5p and high expression of FAP (Homo
      sapiens fibroblast activation protein alpha) in oral cancerous tissues and their
      negative correlation. Then, the target relationship between miR-30a-5p and FAP
      was validated by dual luciferase reporter assay and biotin-coupled miRNA pulldown
      assay. After transfection in Tca-8113 cells and SCC-15 cells, MTT, colony
      formation, Transwell, and wound healing assays were performed to investigate how
      miR-30a-5p and FAP adjusted propagation, invasiveness, and migration,
      respectively. Mounting evidence supported that miR-30a-5p directly targetted FAP
      and suppressed its expression in oral cavity cancer cells (OSCCs). By suppressing
      FAP expression, miR-30a-5p significantly inhibited cell propagation, migration,
      and invasion. Therefore, miR-30a-5p might be a new therapeutic target for oral
      cancer treatment.

PMID- 29026007
TI  - Milk fat components with potential anticancer activity-a review.
AB  - During many years, the milk fat has been unfairly undervalued due to its
      association with higher levels of cardiovascular diseases, dyslipidaemia or
      obesity, among others. However, currently, this relationship is being re
      evaluated because some of the dairy lipid components have been attributed
      potential health benefits. Due to this, and based on the increasing incidence of
      cancer in our society, this review work aims to discuss the state of the art
      concerning scientific evidence of milk lipid components and reported anticancer
      properties. Results from the in vitro and in vivo experiments suggest that
      specific fatty acids (FA) (as butyric acid and conjugated linoleic acid (CLA),
      among others), phospholipids and sphingolipids from milk globule membrane are
      potential anticarcinogenic agents. However, their mechanism of action remains
      still unclear due to limited and inconsistent findings in human studies.

PMID- 29026009
TI  - Inactivated Lactobacillus promotes protection against myocardial ischemia
      reperfusion injury through NF-kappaB pathway.
AB  - Although restoration of blood flow to an ischemic organ is essential to prevent
      irreversible cellular injury, reperfusion may augment tissue injury in excess of
      that produced by ischemia alone. So this experiment was designed to study the
      protective effects and mechanism of inactivated Lactobacillus (Lac) on myocardial
      ischemia-reperfusion (I-R) injury (MIRI). MIRI rat models were established by
      ligation of left anterior descending coronary artery for ~30 min and then,
      reperfusion for 120 min and divided into control group, model group, and Lac
      (106, 107, and 108 cfu/kg) groups. At the end of the test, the creatine kinase
      (CK) activity, lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD)
      activity and malondialdehyde (MDA) content were assayed by corresponding kits.
      The heart was obtained from rats and the myocardial infarction area was
      determined by TTC staining and myocardial endothelial cell apoptosis rate was
      determined by Tunel kit. Besides, A20, IkappaB, nuclear factor (NF)-kappaB, and
      nitric oxide (NO) synthase (NOS) were also assayed by Western blot. When compared
      with model group, Lac obviously reduces MIRI in the rat by reducing myocardial
      infarction area and the apoptosis rate of endothelial cells; reduce the serum CK,
      LDH, and MDA content; increase the serum SOD activity; and suppress NF-kappaB
      signaling and NOS expression in the myocardial tissues. Lac pretreatment can
      inhibit lipid peroxidation and effectively improve MIRI caused by oxygen free
      radical through inhibiting NF-kappaB signaling.

PMID- 29026010
TI  - Cover stories: Making the Orbiting Carbon Observatory-2 cover.

PMID- 29026008
TI  - Abdominal obesity and colorectal cancer risk: systematic review and meta-analysis
      of prospective studies.
AB  - The association between abdominal obesity (as measured by waist circumference
      (WC) and waist-to-hip ratio (WHR)) and colorectal cancer (CRC) has not been fully
      quantified, and the magnitude of CRC risk associated with abdominal obesity is
      still unclear. A meta-analysis of prospective studies was performed to elucidate
      the CRC risk associated with abdominal obesity. Pubmed and Embase were searched
      for studies assessing the association between abdominal obesity and CRC risk.
      Relative risks (RRs) with 95% confidence intervals (95% CIs) were pooled using
      random-effects model of meta-analysis. Nineteen prospective cohort studies from
      eighteen publications were included in this meta-analysis. A total of 12,837 CRC
      cases were identified among 1,343,560 participants. Greater WC and WHR were
      significantly associated with increased risk of total colorectal cancer (WC: RR
      1.42, 95% CI 1.30, 1.55; WHR: RR 1.39, 95% CI 1.25, 1.53), colon cancer (WC: RR
      1.53, 95% CI 1.36, 1.72; WHR: 1.39, 95% CI 1.18, 1.63), and rectal cancer (WC: RR
      1.20, 95% CI 1.03, 1.39; WHR: RR 1.22, 95% CI 1.05, 1.42). Subgroup analyses
      further identified the robustness of the association above. No obvious risk of
      publication bias was observed. In summary, abdominal obesity may play an
      important role in the development of CRC.

PMID- 29026006
TI  - Potential contribution of alveolar epithelial type I cells to pulmonary fibrosis.
AB  - Pulmonary fibrosis (PF) is characterized by inflammation and fibrosis of the
      interstitium and destruction of alveolar histoarchitecture ultimately leading to
      a fatal impairment of lung function. Different concepts describe either a
      dominant role of inflammatory pathways or a disturbed remodeling of resident
      cells of the lung parenchyma during fibrogenesis. Further, a combination of both
      the mechanisms has been postulated. The present review emphasizes the particular
      involvement of alveolar epithelial type I cells in all these processes, their
      contribution to innate immune/inflammatory functions and maintenance of proper
      alveolar barrier functions. Amongst the different inflammatory and repair events
      the purinergic receptor P2X7, an ATP-gated cationic channel that regulates not
      only apoptosis, necrosis, autophagy, and NLPR3 inflammosome activation, but also
      the turnover of diverse tight junction (TJ) and water channel proteins, seems to
      be essential for the stability of alveolar barrier integrity and for the
      interaction with protective factors during lung injury.

PMID- 29026011
TI  - Contrasting carbon cycle responses of the tropical continents to the 2015-2016 El
      Nino.
AB  - The 2015-2016 El Nino led to historically high temperatures and low precipitation
      over the tropics, while the growth rate of atmospheric carbon dioxide (CO2) was
      the largest on record. Here we quantify the response of tropical net biosphere
      exchange, gross primary production, biomass burning, and respiration to these
      climate anomalies by assimilating column CO2, solar-induced chlorophyll
      fluorescence, and carbon monoxide observations from multiple satellites. Relative
      to the 2011 La Nina, the pantropical biosphere released 2.5 +/- 0.34 gigatons
      more carbon into the atmosphere in 2015, consisting of approximately even
      contributions from three tropical continents but dominated by diverse carbon
      exchange processes. The heterogeneity of the carbon-exchange processes indicated
      here challenges previous studies that suggested that a single dominant process
      determines carbon cycle interannual variability.

PMID- 29026012
TI  - The Orbiting Carbon Observatory-2 early science investigations of regional carbon
      dioxide fluxes.
AB  - NASA's Orbiting Carbon Observatory-2 (OCO-2) mission was motivated by the need to
      diagnose how the increasing concentration of atmospheric carbon dioxide (CO2) is
      altering the productivity of the biosphere and the uptake of CO2 by the oceans.
      Launched on 2 July 2014, OCO-2 provides retrievals of the column-averaged CO2 dry
      air mole fraction ([Formula: see text]) as well as the fluorescence from
      chlorophyll in terrestrial plants. The seasonal pattern of uptake by the
      terrestrial biosphere is recorded in fluorescence and the drawdown of [Formula:
      see text] during summer. Launched just before one of the most intense El Ninos of
      the past century, OCO-2 measurements of [Formula: see text] and fluorescence
      record the impact of the large change in ocean temperature and rainfall on uptake
      and release of CO2 by the oceans and biosphere.

PMID- 29026013
TI  - OCO-2 advances photosynthesis observation from space via solar-induced
      chlorophyll fluorescence.
AB  - Quantifying gross primary production (GPP) remains a major challenge in global
      carbon cycle research. Spaceborne monitoring of solar-induced chlorophyll
      fluorescence (SIF), an integrative photosynthetic signal of molecular origin, can
      assist in terrestrial GPP monitoring. However, the extent to which SIF tracks
      spatiotemporal variations in GPP remains unresolved. Orbiting Carbon Observatory
      2 (OCO-2)'s SIF data acquisition and fine spatial resolution permit direct
      validation against ground and airborne observations. Empirical orthogonal
      function analysis shows consistent spatiotemporal correspondence between OCO-2
      SIF and GPP globally. A linear SIF-GPP relationship is also obtained at eddy-flux
      sites covering diverse biomes, setting the stage for future investigations of the
      robustness of such a relationship across more biomes. Our findings support the
      central importance of high-quality satellite SIF for studying terrestrial carbon
      cycle dynamics.

PMID- 29026014
TI  - Influence of El Nino on atmospheric CO2 over the tropical Pacific Ocean: Findings
      from NASA's OCO-2 mission.
AB  - Spaceborne observations of carbon dioxide (CO2) from the Orbiting Carbon
      Observatory-2 are used to characterize the response of tropical atmospheric CO2
      concentrations to the strong El Nino event of 2015-2016. Although correlations
      between the growth rate of atmospheric CO2 concentrations and the El Nino
      Southern Oscillation are well known, the magnitude of the correlation and the
      timing of the responses of oceanic and terrestrial carbon cycle remain poorly
      constrained in space and time. We used space-based CO2 observations to confirm
      that the tropical Pacific Ocean does play an early and important role in
      modulating the changes in atmospheric CO2 concentrations during El Nino events-a
      phenomenon inferred but not previously observed because of insufficient high
      density, broad-scale CO2 observations over the tropics.

PMID- 29026015
TI  - Spaceborne detection of localized carbon dioxide sources.
AB  - Spaceborne measurements by NASA's Orbiting Carbon Observatory-2 (OCO-2) at the
      kilometer scale reveal distinct structures of atmospheric carbon dioxide (CO2)
      caused by known anthropogenic and natural point sources. OCO-2 transects across
      the Los Angeles megacity (USA) show that anthropogenic CO2 enhancements peak over
      the urban core and decrease through suburban areas to rural background values
      more than ~100 kilometers away, varying seasonally from ~4.4 to 6.1 parts per
      million. A transect passing directly downwind of the persistent isolated natural
      CO2 plume from Yasur volcano (Vanuatu) shows a narrow filament of enhanced CO2
      values (~3.4 parts per million), consistent with a CO2 point source emitting 41.6
      kilotons per day. These examples highlight the potential of the OCO-2 sensor,
      with its unprecedented resolution and sensitivity, to detect localized natural
      and anthropogenic CO2 sources.

PMID- 29026016
TI  - Comment on "Selective anaerobic oxidation of methane enables direct synthesis of
      methanol".
AB  - Sushkevich et al (Reports, 5 May 2017, p. 523) report on the use of water to
      oxidize methane to methanol. This seems problematic because the reaction of CH4
      and water to generate methanol and H2 is highly unfavorable at any temperature
      (DeltaG of reaction ~ +28 kcal/mol at 200 degrees C, equilibrium constant K ~ 10
      13). Consequently, even if the reaction is separated into two steps, it seems
      inconceivable to carry out such a net reaction in a practical manner.

PMID- 29026017
TI  - Response to Comment on "Selective anaerobic oxidation of methane enables direct
      synthesis of methanol".
AB  - Periana argues that the stepwise reaction of methane with water is
      thermodynamically unfavorable and therefore impractical. We reply by presenting
      an in-depth thermodynamic analysis of each step in the process and show that the
      surface concentrations of the reactants and products as well as the stabilizing
      effect of additional water molecules, as discussed in the original paper, fully
      support the feasibility of the proposed reaction.

PMID- 29026018
TI  - Rebuilding Caribbean science.

PMID- 29026020
TI  - Drug-resistant malaria advances in Mekong.

PMID- 29026021
TI  - Cold, clear view of molecules nets chemistry prize.

PMID- 29026022
TI  - How Africans evolved a palette of skin tones.

PMID- 29026023
TI  - Evolution accelerated when life set foot on land.

PMID- 29026025
TI  - Most distant Milky Way outpost mapped.

PMID- 29026024
TI  - 'Science wars' veteran has a new mission.

PMID- 29026027
TI  - A cold case.

PMID- 29026026
TI  - Publishers take academic networking site to court.

PMID- 29026028
TI  - Addressing supply issues for natural products in the clinic.

PMID- 29026029
TI  - A direct look at halogen bonds.

PMID- 29026030
TI  - Helping robots blend into the background.

PMID- 29026031
TI  - Quantum emitters in two dimensions.

PMID- 29026032
TI  - Life, death, and antibodies.

PMID- 29026033
TI  - Atlas...t, patterns from every cell.

PMID- 29026034
TI  - Sir Patrick Bateson (1938-2017).

PMID- 29026035
TI  - Reproductive health in culture wars crossfire.

PMID- 29026036
TI  - Brazil's development turns river into sea.

PMID- 29026037
TI  - Brazil's scientists and churches share goals.

PMID- 29026038
TI  - Sand in demand: Trapped behind dams.

PMID- 29026039
TI  - Measuring Earth's carbon cycle.

PMID- 29026040
TI  - Stretchable surfaces with programmable 3D texture morphing for synthetic
      camouflaging skins.
AB  - Technologies that use stretchable materials are increasingly important, yet we
      are unable to control how they stretch with much more sophistication than
      inflating balloons. Nature, however, demonstrates remarkable control of
      stretchable surfaces; for example, cephalopods can project hierarchical
      structures from their skin in milliseconds for a wide range of textural
      camouflage. Inspired by cephalopod muscular morphology, we developed synthetic
      tissue groupings that allowed programmable transformation of two-dimensional (2D)
      stretchable surfaces into target 3D shapes. The synthetic tissue groupings
      consisted of elastomeric membranes embedded with inextensible textile mesh that
      inflated to within 10% of their target shapes by using a simple fabrication
      method and modeling approach. These stretchable surfaces transform from flat
      sheets to 3D textures that imitate natural stone and plant shapes and camouflage
      into their background environments.

PMID- 29026041
TI  - Anti-Markovnikov alkene oxidation by metal-oxo-mediated enzyme catalysis.
AB  - Catalytic anti-Markovnikov oxidation of alkene feedstocks could simplify
      synthetic routes to many important molecules and solve a long-standing challenge
      in chemistry. Here we report the engineering of a cytochrome P450 enzyme by
      directed evolution to catalyze metal-oxo-mediated anti-Markovnikov oxidation of
      styrenes with high efficiency. The enzyme uses dioxygen as the terminal oxidant
      and achieves selectivity for anti-Markovnikov oxidation over the kinetically
      favored alkene epoxidation by trapping high-energy intermediates and catalyzing
      an oxo transfer, including an enantioselective 1,2-hydride migration. The anti
      Markovnikov oxygenase can be combined with other catalysts in synthetic metabolic
      pathways to access a variety of challenging anti-Markovnikov functionalization
      reactions.

PMID- 29026043
TI  - Mapping spiral structure on the far side of the Milky Way.
AB  - Little is known about the portion of the Milky Way lying beyond the Galactic
      center at distances of more than 9 kiloparsec from the Sun. These regions are
      opaque at optical wavelengths because of absorption by interstellar dust, and
      distances are very large and hard to measure. We report a direct trigonometric
      parallax distance of [Formula: see text] kiloparsec obtained with the Very Long
      Baseline Array to a water maser source in a region of active star formation.
      These measurements allow us to shed light on Galactic spiral structure by
      locating the Scutum-Centaurus spiral arm as it passes through the far side of the
      Milky Way and to validate a kinematic method for determining distances in this
      region on the basis of transverse motions.

PMID- 29026042
TI  - Scalable synthesis of bryostatin 1 and analogs, adjuvant leads against latent
      HIV.
AB  - Bryostatin 1 is an exceedingly scarce marine-derived natural product that is in
      clinical development directed at HIV/AIDS eradication, cancer immunotherapy, and
      the treatment of Alzheimer's disease. Despite this unique portfolio of
      indications, its availability has been limited and variable, thus impeding
      research and clinical studies. Here, we report a total synthesis of bryostatin 1
      that proceeds in 29 total steps (19 in the longest linear sequence, >80% average
      yield per step), collectively produces grams of material, and can be scaled to
      meet clinical needs (~20 grams per year). This practical solution to the
      bryostatin supply problem also opens broad, facile, and efficient access to
      derivatives and potentially superior analogs.

PMID- 29026045
TI  - I am a United Academic Worker.

PMID- 29026046
TI  - Doctor for Society: paying tribute to role models of humanitarianism and
      professionalism.

PMID- 29026044
TI  - Innovative scattering analysis shows that hydrophobic disordered proteins are
      expanded in water.
AB  - A substantial fraction of the proteome is intrinsically disordered, and even well
      folded proteins adopt non-native geometries during synthesis, folding, transport,
      and turnover. Characterization of intrinsically disordered proteins (IDPs) is
      challenging, in part because of a lack of accurate physical models and the
      difficulty of interpreting experimental results. We have developed a general
      method to extract the dimensions and solvent quality (self-interactions) of IDPs
      from a single small-angle x-ray scattering measurement. We applied this procedure
      to a variety of IDPs and found that even IDPs with low net charge and high
      hydrophobicity remain highly expanded in water, contrary to the general
      expectation that protein-like sequences collapse in water. Our results suggest
      that the unfolded state of most foldable sequences is expanded; we conjecture
      that this property was selected by evolution to minimize misfolding and
      aggregation.

PMID- 29026047
TI  - Response to the Food and Drug Administration warning on the use of anaesthetics
      in young children.

PMID- 29026048
TI  - Spinal cord stimulation for chronic non-cancer pain: a review of current evidence
      and practice.
AB  - Spinal cord stimulation provides analgesia through electrical stimulation of the
      dorsal column of the spinal cord via electrode leads placed into the epidural
      space. In traditional tonic stimulation, a painful sensation is replaced with
      paraesthesia. Spinal cord stimulation is effective in reducing neuropathic pain,
      enhancing function, and improving quality of life in different chronic pain
      conditions. Currently, there is most evidence to support its use for failed back
      surgery syndrome when multidisciplinary conventional management is unsuccessful.
      Temporary trial leads are inserted in carefully selected patients to test their
      responsiveness prior to permanent implantation. Newer neuromodulation modalities
      are now available. These include burst stimulation, high-frequency stimulation,
      and dorsal root ganglion stimulation. Results are encouraging to date, and they
      may provide superior analgesia and cover for deficiencies of traditional tonic
      stimulation. Although complications are not uncommon, they are rarely life
      threatening or permanently disabling. Nonetheless, device removal is occasionally
      needed.

PMID- 29026049
TI  - Diabetes in older people: position statement of The Hong Kong Geriatrics Society
      and the Hong Kong Society of Endocrinology, Metabolism and Reproduction.
AB  - Following a survey on the clinical practice of geriatricians in the management of
      older people with diabetes and a study of hypoglycaemia in diabetic patients, a
      round-table discussion with geriatricians and endocrinologists was held in
      January 2015. Consensus was reached for six domains specifically related to older
      diabetic people: (1) the considerations when setting an individualised diabetic
      management; (2) inclusion of geriatric syndrome screening in assessment; (3)
      glycaemic and blood pressure targets; (4) pharmacotherapy; (5) restrictive
      diabetic diet; and (6) management goals for nursing home residents.

PMID- 29026050
TI  - Immunoglobulin G4-related sclerosing disease involving the mandible.

PMID- 29026051
TI  - Immunoglobulin G4-related disease masquerading as tonsil carcinoma.

PMID- 29026052
TI  - Can Hong Kong take advantage of recent advances in allergy prevention?

PMID- 29026053
TI  - Obituary: Professor Sir David Todd.

PMID- 29026054
TI  - Functional status and early surgery in elderly patients with hip fracture.

PMID- 29026055
TI  - Childhood lead poisoning: an overview.
AB  - Childhood lead poisoning is a major public health concern in many countries. In
      2015, the Hong Kong SAR Government and its citizens faced a major public health
      crisis due to the presence of lead in the drinking water of a number of public
      housing estates. Fortunately, no child was diagnosed with lead poisoning that
      required treatment with chelation. Lead is a ubiquitous, naturally occurring
      material that exists in air, dust, soil, and water. It is also widely present in
      industrial products including petrol, paints, ceramics, food cans, candies,
      cosmetics, traditional remedies, batteries, solder, stained glass, crystal
      vessels, ammunition, ceramic glazes, jewellry, and toys. It can also be found in
      human milk. There is no safe blood lead level and it may be impossible to
      completely eliminate lead from any city. Hence routine measurement of blood lead
      levels is not considered useful. Acute poisoning, especially with encephalopathy,
      deserves immediate medical treatment in hospital. Chelation therapy is
      recommended if blood lead level is 45 MUg/dL or higher. For blood levels between
      20 and 45 MUg/dL, treatment is indicated if the child is symptomatic. For blood
      levels below 20 MUg/dL in otherwise asymptomatic children, the principle of
      treatment is to provide long-term neurodevelopmental follow-up and counselling.
      In all cases, immediate removal of the source of lead exposure is vital. Even low
      levels of lead exposure can significantly impair learning, educational
      attainment, and neurodevelopment.

PMID- 29026056
TI  - Patient opinion of lower urinary tract symptoms and their treatment: a cross
      sectional survey in Hong Kong public urology clinics.
AB  - INTRODUCTION: Lower urinary tract symptoms collectively represent a common
      condition among ageing men. There are, however, limited data on the frequency of
      individual symptoms in patients who seek specialist care. We conducted a
      multinational survey in South-East Asia to evaluate patients' self-reported
      prevalence, bother, treatment, and treatment satisfaction of four lower urinary
      tract symptoms namely, urgency, nocturia, slow stream, and post-micturition
      dribble. This report presents the analysis of the Hong Kong subpopulation.
      METHODS: This cross-sectional survey involved adult men aged over 18 years who
      attended a urology out-patient clinic because of lower urinary tract symptoms. A
      structured questionnaire, translated and validated in the local languages, was
      self-administered by patients. RESULTS: Of 1436 respondents surveyed in the
      region, 225 were from Hong Kong of whom most were aged 56 to 75 years, retired,
      and had no history of any previous prostate surgery. Overall, the self-reported
      prevalence of nocturia of at least one void per night was 93% (95% confidence
      interval, 90%-97%), slow stream 76% (71%-82%), post-micturition dribble 70% (64%
      76%), and urgency 50% (43%-56%). Symptoms for which most respondents reported
      "some" or "a lot" of bother included: nocturia, defined as at least two voids per
      night (77%), and urgency and post-micturition dribble (73%). Only 39% to 54% of
      patients had previously received treatment but were not entirely satisfied with
      it. An understanding of their condition remained suboptimal. CONCLUSIONS: In Hong
      Kong, nocturia emerged as the most prevalent and one of the most bothersome
      symptoms among men who sought urologist care for lower urinary tract symptoms.
      Compared with the non-Hong Kong population, Hong Kong respondents tended to be
      highly symptomatic and bothered. They were, however, less likely to have received
      treatment and were generally less satisfied with previous treatment.

PMID- 29026057
TI  - Pathological outcome for Chinese patients with low-risk prostate cancer eligible
      for active surveillance and undergoing radical prostatectomy: comparison of six
      different active surveillance protocols.
AB  - INTRODUCTION: Active surveillance is one of the therapeutic options for the
      management of patients with low-risk prostate cancer. This study compared the
      performance of six different active surveillance protocols for prostate cancer in
      the Chinese population. METHODS: Patients who underwent radical prostatectomy for
      prostate cancer from January 1998 to December 2012 at a university teaching
      hospital in Hong Kong were reviewed. Six active surveillance protocols were
      applied to the cohort. Statistical analyses were performed to compare the
      probabilities of missing unfavourable pathological outcome. The sensitivity and
      specificity of each protocol in identifying low-risk disease were compared.
      RESULTS: During the study period, 287 patients were included in the cohort.
      Depending on different active surveillance protocols used, extracapsular
      extension, seminal vesicle invasion, pathological T3 disease, and upgrading of
      Gleason score were present on final pathology in 3.3%-17.1%, 0%-3.3%, 3.3%-19.1%,
      and 20.6%-34.5% of the patients, respectively. The University of Toronto protocol
      had a higher rate of extracapsular extension at 17.1% and pathological T3 disease
      at 19.1% on final pathology than the more stringent protocols from John Hopkins
      (3.3% extracapsular extension, P=0.05 and 3.3% pathological T3 disease, P=0.03)
      and Prostate Cancer Research International: Active Surveillance (PRIAS; 8.0%
      pathological T3 disease, P=0.04). The Royal Marsden protocol had a higher rate of
      upgrading of Gleason score at 34.5% compared with the more stringent protocol of
      PRIAS at 20.6% (P=0.04). The specificities in identifying localised disease and
      low-risk histology among different active surveillance protocols were 59%-98% and
      58%-94%, respectively. The John Hopkins active surveillance protocol had the
      highest specificity in both selecting localised disease (98%) and low-risk
      histology (94%). CONCLUSIONS: Active surveillance protocols based on prostate
      specific antigen and Gleason score alone or including Gleason score of 3+4 may
      miss high-risk disease and should be used cautiously. The John Hopkins and PRIAS
      protocols are highly specific in identifying localised disease and low-risk
      histology.

PMID- 29026058
TI  - Clinical utility of late-night and post-overnight dexamethasone suppression
      salivary cortisone for the investigation of Cushing's syndrome.
AB  - INTRODUCTION: There is a pressing need to identify diagnostic testing for
      Cushing's syndrome that can be achieved with ease and at low cost. This study
      aimed to explore the usefulness of late-night and post-overnight 1-mg
      dexamethasone suppression salivary cortisone, as measured by liquid
      chromatography-tandem mass spectrometry, for investigation of hypercortisolism.
      METHODS: Salivary cortisone data of subjects were investigated according to a pre
      specified protocol. Subjects were classified as having 'hypercortisolism' or
      'eucortisolism' on the basis of histological or biochemical criteria. Receiver
      operating characteristic curves were drawn to identify the cut-off values and
      study their performance characteristics. We measured 24-hour urinary free
      cortisol; late-night salivary cortisol and cortisone; and post-overnight 1-mg
      dexamethasone suppression serum cortisol, and salivary cortisol and cortisone.
      Saliva and urine samples were assayed by liquid chromatography-tandem mass
      spectrometry. RESULTS: In this study, 21 subjects were classified as having
      hypercortisolism and 78 as having eucortisolism. A late-night salivary cortisone
      cut-off of 13.50 nmol/L had a sensitivity of 94.7% and a specificity of 87.2%.
      After taking 1-mg dexamethasone the night before, a salivary cortisol cut-off of
      0.85 nmol/L had a sensitivity of 76.2% and a specificity of 96.2%; a salivary
      cortisone cut-off of 7.45 nmol/L had a sensitivity of 85.7% and a specificity of
      94.9%, while a salivary cortisone cut-off of 3.25 nmol/L had a sensitivity of
      95.2% and a specificity of 79.5%. Many salivary cortisol samples were below the
      detection limit of liquid chromatography-tandem mass spectrometry. In comparison
      with salivary cortisol, salivary cortisone had a better correlation with total
      serum cortisol and better diagnostic performance following dexamethasone
      suppression. CONCLUSIONS: Both late-night and post-overnight dexamethasone
      suppression salivary cortisone levels are of diagnostic value in the
      investigation of hypercortisolism.

PMID- 29026061
TI  - Humidifier disinfectant-associated specific diseases should be called together as
      "humidifier disinfectant syndrome".
AB  - Humidifier disinfectant (HD) damage was terrible chemical damage caused by
      household goods that happened in only South Korea, but still very little is known
      in HD damage. Up to now, previous research tried to focus on interstitial
      fibrosis on terminal bronchioles and alveoli because it is a specific finding,
      compared with other diseases. To figure out whole effects from HDs, much
      epidemiologic and toxicologic research is underway. HDs were shown to give rise
      to typical toxicologic effects on various target organs, such as skin,
      conjunctiva, naval mucosa, bronchial mucosa, alveoli and so on, which shared
      common toxicological responses. On a specific target, specific toxicologic
      effects existed. Diverse diseases along exposure pathways can occur at the same
      time with a common toxicologic mechanism and cause of HDs, which can be called as
      HD syndrome. To gain stronger scientific evidence about it, further
      epidemiological and toxicological studies should be applied.

PMID- 29026062
TI  - Causal inference in environmental epidemiology.
AB  - Inferring causality is necessary to achieve the goal of epidemiology, which is to
      elucidate the cause of disease. Causal inference is conducted in three steps:
      evaluation of validity of the study, inference of general causality, and
      inference of individual causality. To evaluate validity of the study, we propose
      a checklist that focuses on biases and generalizability. For general causal
      inference, we recommend utilizing Hill's 9 viewpoints. Lastly, individual
      causality can be inferred based on the general causality and evidence of
      exposure. Additional considerations may be needed for social or legal purposes;
      however, these additional considerations should be based on the scientific truth
      elucidated by the causal inference described in the present article.

PMID- 29026060
TI  - Unmet needs in health training among nurses in rural Chinese township health
      centers: a cross-sectional hospital-based study.
AB  - PURPOSE: Maintaining a sufficient and competent rural nursing workforce is an
      important goal of the Chinese health delivery system. However, few studies have
      investigated the health training status or conducted a needs assessment of rural
      Chinese nurses during this time of great transformations in health policy. This
      study was conducted to explore the current health training status of nurses
      working in rural Chinese township health centers (THCs) and to ascertain their
      perceived needs. METHODS: A cross-sectional survey using a self-administered
      structured questionnaire was conducted among 240 THC nurses in Guangxi Zhuang
      Autonomous Region, China from March 2014 to August 2014. The survey questionnaire
      was adapted from the Second Chinese Survey of Demographic Data and Training
      Demand for Health Professionals in THCs developed by the Ministry of Education.
      RESULTS: The nurses in THCs were young, with a low educational level. Their
      perceived needs for health training included further clinical studies at city
      level hospitals to improve their skills and theoretical studies at medical
      universities in emergency medicine and general practice. Overall, 71.9% of the
      nurses with a secondary technical school background expected to pursue junior
      college studies, and 68.5% of the nurses with a junior college education expected
      to pursue a bachelor's degree. A decentralized program with theoretical studies
      at medical universities and practical studies at county hospitals was regarded as
      feasible by 66.9% of the respondents. CONCLUSION: Health-training programs for
      nurses in Chinese THCs must be improved in terms of coverage, delivery mode, and
      content. A decentralized degree-linked training program in which medical
      universities and city hospitals collaborate would be an appropriate mode of
      delivery.

PMID- 29026063
TI  - Morphological transformation induced by silver nanoparticles in a Balb/c 3T3 A31
      1-1 mouse cell model to evaluate in vitro carcinogenic potential.
AB  - Carcinogenesis is a complex process involved in genotoxic and non-genotoxic
      pathways. The carcinogenic potential of silver nanoparticles (AgNPs) has been
      predicted by examining their genotoxic effects using several in vitro and in vivo
      models. However, there is no little information regarding the non-genotoxic
      effects of AgNPs related to carcinogenesis. The in vitro cell transformation
      assay (CTA) provides specific and sensitive evidence for predicting the
      tumorigenic potential of a chemical, which cannot be obtained by genotoxicity
      testing. Therefore, we carried out CTA in Balb/c 3T3 A31-1-1 cells to evaluate
      the carcinogenic potential of AgNPs. Colony-forming efficiency and crystal violet
      assays were carried out to determine the cytotoxicity of AgNPs. A cytokinesis
      block micronucleus (CBMN) assay and CTA were performed using Balb/c 3T3 A31-1-1
      cells to predict the in vitro carcinogenic potential of AgNPs. In the CBMN assay,
      AgNPs (10.6 MUg/mL) induced a significant increase in micronucleus formation
      indicating a genotoxic effect. Thus, AgNPs could be an initiator of
      carcinogenesis. In the CTA, used to assess the carcinogenic potential of AgNPs,
      cells exposed to AgNPs for 72 hours showed significantly induced morphological
      neoplastic transformation at all tested doses (0.17, 0.66, 2.65, 5.30, and 10.60
      MUg/mL), and the transformation frequency was significantly increased in a dose
      dependent manner. These results indicate that short-term exposure (72 hours) to
      AgNPs had in vitro carcinogenetic potency in Balb/c 3T3 A31-1-1 cells.

PMID- 29026064
TI  - The Effect of Recipient Body Mass Index and Its Extremes on Survival and Graft
      Vascular and Biliary Complications After Liver Transplantation: A Single Center
      Retrospective Study.
AB  - BACKGROUND This is the largest UK-based study on the effect of recipient body
      mass index (BMI) and its extremes (BMI <18.5 and BMI >=35 kg/m2) on liver
      transplant (LT) outcomes. Its purpose was to analyze the BMI effect on post-LT
      mortality, graft loss, primary non-function (PNF), and graft vascular and biliary
      complications. MATERIAL AND METHODS Data were retrieved from a single-center LT
      database of 2,115 consecutive patients receiving first LT during period February
      2004 to September 2015. Survivals were compared across the BMI groups; the
      effects of recipient BMI on survival, PNF, and graft vascular and biliary
      complications were analyzed via regression. RESULTS Autoimmune disease and
      nonalcoholic steatohepatitis were prevalent among underweight and morbidly obese
      adults, respectively. Graft survival was similar across BMI classes at 30 days
      and in 1, 2, 5, and 10 years (p=0.75) and on obese versus non-obese (p=0.33). BMI
      <35 kg/m2 versus BMI >=35 kg/m2 mean graft survival was similar (p=0.84). BMI
      <18.5 kg/m2 recipients tended to have inferior mean graft and patient survivals;
      however, the difference was non-significant (p=0.09 and p=0.1 respectively). BMI
      <18.5 kg/m2 recipients were at higher risk of hepatic artery thrombosis (HR,
      1.73, 95% CI 1.73-3, p<0.05). Adult underweight status was an independent HAT
      risk factor (HR 3, 95% CI 1-8.6, p=0.046). BMI class did not affect ischemic
      cholangiopathy risk (p=0.84). However, the overall biliary complication risk
      increased by 3% for every 1 kg/m2 BMI rise. CONCLUSIONS Post-LT survival is
      independent of recipient BMI. Underweight status is linked to higher HAT risk.
      Biliary complication risk increases with rising recipient BMI. After appropriate
      recipient selection, recipient BMI extremes are not a contraindication for LT.

PMID- 29026065
TI  - Urethral Diverticulum Presenting as a Large Vaginal Mass Complicating Pregnancy
      and Delivery.
AB  - BACKGROUND A case report of urethral diverticulum complicating pregnancy is
      presented. The diagnosis and management are challenging because of the rare
      nature of this condition, the varied presentations and differential diagnoses,
      and the possibility of misdiagnosis. CASE REPORT A 25-year-old primigravida with
      scheduled induction of labor at 39 weeks gestation due to gestational diabetes
      mellitus presented for a routine antenatal appointment at 38 weeks and four days.
      On digital cervical examination, she was found to have a large semi-solid
      anterior vaginal mass, shown by trans-vaginal ultrasound to have a nearly solid
      appearance of a 5*7 cm mass with septation. Maternal Fetal Medicine and
      Gynecologic Oncology consultations were obtained primary cesarean section with
      vaginal biopsy in the Operating Room were recommended. Following an uncomplicated
      cesarean delivery and with the patient still under spinal anesthesia, the
      anterior vaginal mass was examined and found to contain 200 ml of purulent
      material. Because a diagnosis of urethral diverticulum was made, a biopsy was not
      performed. The patient was placed on antibiotic prophylaxis for the remainder of
      her hospital course. Follow-up CT scan confirmed a large urethral diverticulum,
      and she was referred to the Fetal Pelvic Medicine and Reconstructive Surgery
      (FPMRS) and Urogynecology units for treatment. CONCLUSIONS Early identification
      of urethral diverticulum during the pregnancy may allow for treatment and a trial
      of labor with vaginal delivery. MRI is the recommended imaging modality in
      identifying urethral diverticulum.

PMID- 29026066
TI  - Aberrant Promoter Methylation of Protocadherin8 (PCDH8) in Serum is a Potential
      Prognostic Marker for Low Gleason Score Prostate Cancer.
AB  - BACKGROUND PCDH8 is a newly-discovered suppressor gene that is frequently
      inactivated by aberrant methylation in several human cancers, including prostate
      cancer. The identification of PCDH8 methylation can be used as a potential
      predictive biomarker. Prostate cancer patients with high Gleason score are
      considered as being at high risk for tumor recurrence and progression, and
      adjuvant therapy is often routinely performed in clinical practice. In the
      present study, we did not measure the methylation of PCDH8 in these patients. The
      main purpose of the present study was to evaluate the clinical significance of
      PCDH8 methylation in serum of prostate cancer patients with low Gleason score.
      MATERIAL AND METHODS PCDH8 methylation in serum samples of 117 patients and 47
      controls was checked by methylation-specific PCR (MSP). Then, we correlated PCDH8
      methylation status with the clinicopathological parameters of prostate cancer
      patients with low Gleason score and patient outcomes. RESULTS We found that PCDH8
      was more frequently methylated in serum samples of patients with prostate cancer
      than in controls. PCDH8 methylation was correlated with advanced clinical stage
      (P=0.021), higher level of preoperative PSA (P=0.008), and positive lymph node
      metastasis (P=0.010). Moreover, patients with PCDH8 methylation had worse
      biochemical recurrence (BCR)-free survival (P<0.001) than patients without.
      Independent prognostic factors for worse BCR-free survival of prostate cancer
      patients with low Gleason score were: PCDH8 methylation in serum (Exp (B)=3.147,
      95% CI: 1.152-7.961, P=0.007), clinical stage (Exp (B)=2.53, 95% CI: 1.032-4.763,
      P=0.025) and lymph node status (Exp (B)=1.476, 95% CI: 1.107-4.572, P=0.042).
      CONCLUSIONS Our study indicated that PCDH8 methylation in serum occurred
      frequently in prostate cancer patients and was correlated with risk factors for
      poor outcome. The methylation of PCDH8 in serum is a potential predictive marker
      for prostate cancer patients with low Gleason score after surgery.

PMID- 29026067
TI  - Designing solid-liquid interphases for sodium batteries.
AB  - Secondary batteries based on earth-abundant sodium metal anodes are desirable for
      both stationary and portable electrical energy storage. Room-temperature sodium
      metal batteries are impractical today because morphological instability during
      recharge drives rough, dendritic electrodeposition. Chemical instability of
      liquid electrolytes also leads to premature cell failure as a result of parasitic
      reactions with the anode. Here we use joint density-functional theoretical
      analysis to show that the surface diffusion barrier for sodium ion transport is a
      sensitive function of the chemistry of solid-electrolyte interphase. In
      particular, we find that a sodium bromide interphase presents an exceptionally
      low energy barrier to ion transport, comparable to that of metallic magnesium. We
      evaluate this prediction by means of electrochemical measurements and direct
      visualization studies. These experiments reveal an approximately three-fold
      reduction in activation energy for ion transport at a sodium bromide interphase.
      Direct visualization of sodium electrodeposition confirms large improvements in
      stability of sodium deposition at sodium bromide-rich interphases.The chemistry
      at the interface between electrolyte and electrode plays a critical role in
      determining battery performance. Here, the authors show that a NaBr enriched
      solid-electrolyte interphase can lower the surface diffusion barrier for sodium
      ions, enabling stable electrodeposition.

PMID- 29026068
TI  - Hollow MnO2 as a tumor-microenvironment-responsive biodegradable nano-platform
      for combination therapy favoring antitumor immune responses.
AB  - Herein, an intelligent biodegradable hollow manganese dioxide (H-MnO2) nano
      platform is developed for not only tumor microenvironment (TME)-specific imaging
      and on-demand drug release, but also modulation of hypoxic TME to enhance cancer
      therapy, resulting in comprehensive effects favoring anti-tumor immune responses.
      With hollow structures, H-MnO2 nanoshells post modification with polyethylene
      glycol (PEG) could be co-loaded with a photodynamic agent chlorine e6 (Ce6), and
      a chemotherapy drug doxorubicin (DOX). The obtained H-MnO2-PEG/C&D would be
      dissociated under reduced pH within TME to release loaded therapeutic molecules,
      and in the meantime induce decomposition of tumor endogenous H2O2 to relieve
      tumor hypoxia. As a result, a remarkable in vivo synergistic therapeutic effect
      is achieved through the combined chemo-photodynamic therapy, which simultaneously
      triggers a series of anti-tumor immune responses. Its further combination with
      checkpoint-blockade therapy would lead to inhibition of tumors at distant sites,
      promising for tumor metastasis treatment.MnO2 nanostructures are promising TME
      responsive theranostic agents in cancer. Here, the authors develop a nano
      platform based on hollow H-MnO2 nanoshells able to modulate the tissue
      microenvironment, release a drug and inhibit tumor growth alone or in combination
      with check-point blockade therapy.

PMID- 29026070
TI  - Single-molecule study of oxidative enzymatic deconstruction of cellulose.
AB  - LPMO (lytic polysaccharide monooxygenase) represents a unique paradigm of
      cellulosic biomass degradation by an oxidative mechanism. Understanding the role
      of LPMO in deconstructing crystalline cellulose is fundamental to the enzyme's
      biological function and will help to specify the use of LPMO in biorefinery
      applications. Here we show with real-time atomic force microscopy that C1 and C4
      oxidizing types of LPMO from Neurospora crassa (NcLPMO9F, NcLPMO9C) bind to
      nanocrystalline cellulose with high preference for the very same substrate
      surfaces that are also used by a processive cellulase (Trichoderma reesei CBH I)
      to move along during hydrolytic cellulose degradation. The bound LPMOs, however,
      are immobile during their adsorbed residence time ( ~ 1.0 min for NcLPMO9F) on
      cellulose. Treatment with LPMO resulted in fibrillation of crystalline cellulose
      and strongly ( >= 2-fold) enhanced the cellulase adsorption. It also increased
      enzyme turnover on the cellulose surface, thus boosting the hydrolytic
      conversion.Understanding the role of enzymes in biomass depolymerization is
      essential for the development of more efficient biorefineries. Here, the authors
      show by atomic force microscopy the real-time mechanism of cellulose
      deconstruction by lytic polysaccharide monooxygenases.

PMID- 29026069
TI  - ID3 regulates the MDC1-mediated DNA damage response in order to maintain genome
      stability.
AB  - MDC1 plays a critical role in the DNA damage response (DDR) by interacting
      directly with several factors including gamma-H2AX. However, the mechanism by
      which MDC1 is recruited to damaged sites remains elusive. Here, we show that MDC1
      interacts with a helix-loop-helix (HLH)-containing protein called inhibitor of
      DNA-binding 3 (ID3). In response to double-strand breaks (DSBs) in the genome,
      ATM phosphorylates ID3 at serine 65 within the HLH motif, and this modification
      allows a direct interaction with MDC1. Moreover, depletion of ID3 results in
      impaired formation of ionizing radiation (IR)-induced MDC1 foci, suppression of
      gamma-H2AX-bound MDC1, impaired DSB repair, cellular hypersensitivity to IR, and
      genomic instability. Disruption of the MDC1-ID3 interaction prevents accumulation
      of MDC1 at sites of DSBs and suppresses DSB repair. Thus, our study uncovers an
      ID3-dependent mechanism of recruitment of MDC1 to DNA damage sites and suggests
      that the ID3-MDC1 interaction is crucial for DDR.MDC1 is a key component of the
      DNA damage response and interacts with several factors such as gamma-H2AX. Here
      the authors show that MDC1 interacts with ID3, facilitating MDC1 recruitment to
      sites of damage and repair of breaks.

PMID- 29026073
TI  - Causes of model dry and warm bias over central U.S. and impact on climate
      projections.
AB  - Climate models show a conspicuous summer warm and dry bias over the central
      United States. Using results from 19 climate models in the Coupled Model
      Intercomparison Project Phase 5 (CMIP5), we report a persistent dependence of
      warm bias on dry bias with the precipitation deficit leading the warm bias over
      this region. The precipitation deficit is associated with the widespread failure
      of models in capturing strong rainfall events in summer over the central U.S. A
      robust linear relationship between the projected warming and the present-day warm
      bias enables us to empirically correct future temperature projections. By the end
      of the 21st century under the RCP8.5 scenario, the corrections substantially
      narrow the intermodel spread of the projections and reduce the projected
      temperature by 2.5 K, resulting mainly from the removal of the warm bias. Instead
      of a sharp decrease, after this correction the projected precipitation is nearly
      neutral for all scenarios.Climate models repeatedly show a warm and dry bias over
      the central United States, but the origin of this bias remains unclear. Here the
      authors associate this bias to precipitation deficits in models and after
      applying a correction, projected precipitation in this region shows no
      significant changes.

PMID- 29026072
TI  - Dynamic regulation of canonical TGFbeta signalling by endothelial transcription
      factor ERG protects from liver fibrogenesis.
AB  - The role of the endothelium in protecting from chronic liver disease and TGFbeta
      mediated fibrosis remains unclear. Here we describe how the endothelial
      transcription factor ETS-related gene (ERG) promotes liver homoeostasis by
      controlling canonical TGFbeta-SMAD signalling, driving the SMAD1 pathway while
      repressing SMAD3 activity. Molecular analysis shows that ERG binds to SMAD3,
      restricting its access to DNA. Ablation of ERG expression results in endothelial
      to-mesenchymal transition (EndMT) and spontaneous liver fibrogenesis in EC
      specific constitutive hemi-deficient (Erg cEC-Het ) and inducible homozygous
      deficient mice (Erg iEC-KO ), in a SMAD3-dependent manner. Acute administration
      of the TNF-alpha inhibitor etanercept inhibits carbon tetrachloride (CCL4)
      induced fibrogenesis in an ERG-dependent manner in mice. Decreased ERG expression
      also correlates with EndMT in tissues from patients with end-stage liver
      fibrosis. These studies identify a pathogenic mechanism where loss of ERG causes
      endothelial-dependent liver fibrogenesis via regulation of SMAD2/3. Moreover, ERG
      represents a promising candidate biomarker for assessing EndMT in liver
      disease.The transcription factor ERG is key to endothelial lineage specification
      and vascular homeostasis. Here the authors show that ERG balances TGFbeta
      signalling through the SMAD1 and SMAD3 pathways, protecting the endothelium from
      endothelial-to-mesenchymal transition and consequent liver fibrosis in mice via a
      SMAD3-dependent mechanism.

PMID- 29026071
TI  - Arginine methylation catalyzed by PRMT1 is required for B cell activation and
      differentiation.
AB  - Arginine methylation catalyzed by protein arginine methyltransferases (PRMT) is a
      common post-translational modification in mammalian cells, regulating many
      important functions including cell signalling, proliferation and differentiation.
      Here we show the role of PRMT1 in B-cell activation and differentiation. PRMT1
      expression and activity in human and mouse peripheral B cells increases in
      response to in vitro or in vivo activation. Deletion of the Prmt1 gene in mature
      B cells establishes that although the frequency and phenotype of peripheral B
      cell subsets seem unaffected, immune responses to T-cell-dependent and 
      independent antigens are substantially reduced. In vitro activation of Prmt1
      deficient B cells with a variety of mitogens results in diminished proliferation,
      differentiation and survival, effects that are correlated with altered signal
      transduction from the B cell receptor. Thus PRMT1 activity in B cells is required
      for correct execution of multiple processes that in turn are necessary for
      humoral immunity.PRMT1 is an arginine methyltransferase involved in a variety of
      cell functions. Here the authors delete PRMT1 specifically in mature B cells to
      show the importance of arginine methylation for B cell proliferation,
      differentiation and survival, and thereby for humoral immunity.

PMID- 29026074
TI  - Structural insights into the competitive inhibition of the ATP-gated P2X receptor
      channel.
AB  - P2X receptors are non-selective cation channels gated by extracellular ATP, and
      the P2X7 receptor subtype plays a crucial role in the immune and nervous systems.
      Altered expression and dysfunctions of P2X7 receptors caused by genetic
      deletions, mutations, and polymorphic variations have been linked to various
      diseases, such as rheumatoid arthritis and hypertension. Despite the availability
      of crystal structures of P2X receptors, the mechanism of competitive antagonist
      action for P2X receptors remains controversial. Here, we determine the crystal
      structure of the chicken P2X7 receptor in complex with the competitive P2X
      antagonist, TNP-ATP. The structure reveals an expanded, incompletely activated
      conformation of the channel, and identified the unique recognition manner of TNP
      ATP, which is distinct from that observed in the previously determined human P2X3
      receptor structure. A structure-based computational analysis furnishes
      mechanistic insights into the TNP-ATP-dependent inhibition. Our work provides
      structural insights into the functional mechanism of the P2X competitive
      antagonist.P2X receptors are nonselective cation channels that are gated by
      extracellular ATP. Here the authors present the crystal structure of chicken P2X7
      with its bound competitive antagonist TNP-ATP and give mechanistic insights into
      TNP-ATP dependent inhibition through further computational analysis and
      electrophysiology measurements.

PMID- 29026075
TI  - Evidence of a chimpanzee-sized ancestor of humans but a gibbon-sized ancestor of
      apes.
AB  - Body mass directly affects how an animal relates to its environment and has a
      wide range of biological implications. However, little is known about the mass of
      the last common ancestor (LCA) of humans and chimpanzees, hominids (great apes
      and humans), or hominoids (all apes and humans), which is needed to evaluate
      numerous paleobiological hypotheses at and prior to the root of our lineage. Here
      we use phylogenetic comparative methods and data from primates including humans,
      fossil hominins, and a wide sample of fossil primates including Miocene apes from
      Africa, Europe, and Asia to test alternative hypotheses of body mass evolution.
      Our results suggest, contrary to previous suggestions, that the LCA of all
      hominoids lived in an environment that favored a gibbon-like size, but a series
      of selective regime shifts, possibly due to resource availability, led to a
      decrease and then increase in body mass in early hominins from a chimpanzee-sized
      LCA.The pattern of body size evolution in hominids can provide insight into
      historical human ecology. Here, Grabowski and Jungers use comparative
      phylogenetic analysis to reconstruct the likely size of the ancestor of humans
      and chimpanzees and the evolutionary history of selection on body size in
      primates.

PMID- 29026076
TI  - Sample composition alters associations between age and brain structure.
AB  - Despite calls to incorporate population science into neuroimaging research, most
      studies recruit small, non-representative samples. Here, we examine whether
      sample composition influences age-related variation in global measurements of
      gray matter volume, thickness, and surface area. We apply sample weights to
      structural brain imaging data from a community-based sample of children aged 3-18
      (N = 1162) to create a "weighted sample" that approximates the distribution of
      socioeconomic status, race/ethnicity, and sex in the U.S. Census. We compare
      associations between age and brain structure in this weighted sample to estimates
      from the original sample with no sample weights applied (i.e., unweighted).
      Compared to the unweighted sample, we observe earlier maturation of cortical and
      sub-cortical structures, and patterns of brain maturation that better reflect
      known developmental trajectories in the weighted sample. Our empirical
      demonstration of bias introduced by non-representative sampling in this
      neuroimaging cohort suggests that sample composition may influence understanding
      of fundamental neural processes.The influence of sample composition on human
      neuroimaging results is unknown. Here, the authors weight a large, community
      based sample to better reflect the US population and describe how applying these
      sample weights changes conclusions about age-related variation in brain
      structure.

PMID- 29026077
TI  - Coulomb spin liquid in anion-disordered pyrochlore Tb2Hf2O7.
AB  - The charge ordered structure of ions and vacancies characterizing rare-earth
      pyrochlore oxides serves as a model for the study of geometrically frustrated
      magnetism. The organization of magnetic ions into networks of corner-sharing
      tetrahedra gives rise to highly correlated magnetic phases with strong
      fluctuations, including spin liquids and spin ices. It is an open question how
      these ground states governed by local rules are affected by disorder. Here we
      demonstrate in the pyrochlore Tb2Hf2O7, that the vicinity of the disordering
      transition towards a defective fluorite structure translates into a tunable
      density of anion Frenkel disorder while cations remain ordered. Quenched random
      crystal fields and disordered exchange interactions can therefore be introduced
      into otherwise perfect pyrochlore lattices of magnetic ions. We show that
      disorder can play a crucial role in preventing long-range magnetic order at low
      temperatures, and instead induces a strongly fluctuating Coulomb spin liquid with
      defect-induced frozen magnetic degrees of freedom.Experimental studies of
      frustrated spin systems such as pyrochlore magnetic oxides test our understanding
      of quantum many-body physics. Here the authors show experimentally that Tb2Hf2O7
      may be a model material for investigating how structural disorder can stabilize a
      quantum spin liquid phase.

PMID- 29026078
TI  - Deciphering TAL effectors for 5-methylcytosine and 5-hydroxymethylcytosine
      recognition.
AB  - DNA recognition by transcription activator-like effector (TALE) proteins is
      mediated by tandem repeats that specify nucleotides through repeat-variable
      diresidues. These repeat-variable diresidues form direct and sequence-specific
      contacts to DNA bases; hence, TALE-DNA interaction is sensitive to DNA chemical
      modifications. Here we conduct a thorough investigation, covering all theoretical
      repeat-variable diresidue combinations, for their recognition capabilities for 5
      methylcytosine and 5-hydroxymethylcytosine, two important epigenetic markers in
      higher eukaryotes. We identify both specific and degenerate repeat-variable
      diresidues for 5-methylcytosine and 5-hydroxymethylcytosine. Utilizing these
      novel repeat-variable diresidues, we achieve methylation-dependent gene
      activation and genome editing in vivo; we also report base-resolution detection
      of 5hmC in an in vitro assay. Our work deciphers repeat-variable diresidues for 5
      methylcytosine and 5-hydroxymethylcytosine, and provides tools for TALE-dependent
      epigenome recognition.Transcription activator-like effector proteins recognise
      specific DNA sequences via tandem repeats. Here the authors demonstrate TALEs can
      recognise the methylated bases 5mC and 5hmC, enabling them to detect epigenetic
      modifications.

PMID- 29026079
TI  - A long-range cis-regulatory element for class I odorant receptor genes.
AB  - Individual olfactory sensory neurons express a single odorant receptor gene from
      either class I genes residing in a single cluster on a single chromosome or class
      II genes spread over multiple clusters on multiple chromosomes. Here, we identify
      an enhancer element for mouse class I genes, the J element, that is conserved
      through mammalian species from the platypus to humans. The J element regulates
      most class I genes expression by exerting an effect over ~ 3 megabases within the
      whole cluster. Deletion of the trans J element increases the expression
      frequencies of class I genes from the intact J allele, indicating that the
      allelic exclusion of class I genes depends on the activity of the J element. Our
      data reveal a long-range cis-regulatory element that governs the singular class I
      gene expression and has been phylogenetically preserved to retain a single
      cluster organization of class I genes in mammals."Each olfactory sensory neuron
      expresses a single odorant receptor gene from either class I or class II genes.
      Here, the authors identify an enhancer for mouse class I genes, that is highly
      conserved, and regulates most class I genes expression by acting over ~ 3
      megabases within the whole cluster."

PMID- 29026080
TI  - All-optical regenerator of multi-channel signals.
AB  - One of the main reasons why nonlinear-optical signal processing (regeneration,
      logic, etc.) has not yet become a practical alternative to electronic processing
      is that the all-optical elements with nonlinear input-output relationship have
      remained inherently single-channel devices (just like their electronic
      counterparts) and, hence, cannot fully utilise the parallel processing potential
      of optical fibres and amplifiers. The nonlinear input-output transfer function
      requires strong optical nonlinearity, e.g. self-phase modulation, which, for
      fundamental reasons, is always accompanied by cross-phase modulation and four
      wave mixing. In processing multiple wavelength-division-multiplexing channels,
      large cross-phase modulation and four-wave mixing crosstalks among the channels
      destroy signal quality. Here we describe a solution to this problem: an optical
      signal processor employing a group-delay-managed nonlinear medium where strong
      self-phase modulation is achieved without such nonlinear crosstalk. We
      demonstrate, for the first time to our knowledge, simultaneous all-optical
      regeneration of up to 16 wavelength-division-multiplexing channels by one device.
      This multi-channel concept can be extended to other nonlinear-optical processing
      schemes.Nonlinear optical processing devices are not yet fully practical as they
      are single channel. Here the authors demonstrate all-optical regeneration of up
      to 16 channels by one device, employing a group-delay-managed nonlinear medium
      where strong self-phase modulation is achieved without nonlinear inter-channel
      crosstalk.

PMID- 29026081
TI  - Extracellular matrix stiffness and cell contractility control RNA localization to
      promote cell migration.
AB  - Numerous RNAs are enriched within cellular protrusions, but the underlying
      mechanisms are largely unknown. We had shown that the APC (adenomatous polyposis
      coli) protein controls localization of some RNAs at protrusions. Here, using
      protrusion-isolation schemes and RNA-Seq, we find that RNAs localized in
      protrusions of migrating fibroblasts can be distinguished in two groups, which
      are differentially enriched in distinct types of protrusions, and are
      additionally differentially dependent on APC. APC-dependent RNAs become enriched
      in high-contractility protrusions and, accordingly, their localization is
      promoted by increasing stiffness of the extracellular matrix. Dissecting the
      underlying mechanism, we show that actomyosin contractility activates a RhoA
      mDia1 signaling pathway that leads to formation of a detyrosinated-microtubule
      network, which in turn is required for localization of APC-dependent RNAs.
      Importantly, a competition-based approach to specifically mislocalize APC
      dependent RNAs suggests that localization of the APC-dependent RNA subgroup is
      functionally important for cell migration.Adenomatous polyposis coli (APC)
      regulates the localization of some mRNAs at cellular protrusions but the
      underlying mechanisms and functional roles are not known. Here the authors show
      that APC-dependent RNAs are enriched in contractile protrusions, via
      detyrosinated microtubules, and enhance cell migration.

PMID- 29026083
TI  - Chemical signal activation of an organocatalyst enables control over soft
      material formation.
AB  - Cells can react to their environment by changing the activity of enzymes in
      response to specific chemical signals. Artificial catalysts capable of being
      activated by chemical signals are rare, but of interest for creating autonomously
      responsive materials. We present an organocatalyst that is activated by a
      chemical signal, enabling temporal control over reaction rates and the formation
      of materials. Using self-immolative chemistry, we design a deactivated aniline
      organocatalyst that is activated by the chemical signal hydrogen peroxide and
      catalyses hydrazone formation. Upon activation of the catalyst, the rate of
      hydrazone formation increases 10-fold almost instantly. The responsive
      organocatalyst enables temporal control over the formation of gels featuring
      hydrazone bonds. The generic design should enable the use of a large range of
      triggers and organocatalysts, and appears a promising method for the introduction
      of signal response in materials, constituting a first step towards achieving
      communication between artificial chemical systems.Enzymes regulated by chemical
      signals are common in biology, but few such artificial catalysts exist. Here, the
      authors design an aniline catalyst that, when activated by a chemical trigger,
      catalyses formation of hydrazone-based gels, demonstrating signal response in a
      soft material.

PMID- 29026082
TI  - Targeted delivery of celastrol to mesangial cells is effective against
      mesangioproliferative glomerulonephritis.
AB  - Mesangial cells-mediated glomerulonephritis is a frequent cause of end-stage
      renal disease. Here, we show that celastrol is effective in treating both
      reversible and irreversible mesangioproliferative glomerulonephritis in rat
      models, but find that its off-target distributions cause severe systemic
      toxicity. We thus target celastrol to mesangial cells using albumin
      nanoparticles. Celastrol-albumin nanoparticles crosses fenestrated endothelium
      and accumulates in mesangial cells, alleviating proteinuria, inflammation,
      glomerular hypercellularity, and excessive extracellular matrix deposition in rat
      anti-Thy1.1 nephritis models. Celastrol-albumin nanoparticles presents lower drug
      accumulation than free celastrol in off-target organs and tissues, thereby
      minimizing celastrol-related systemic toxicity. Celastrol-albumin nanoparticles
      thus represents a promising treatment option for mesangioproliferative
      glomerulonephritis and similar glomerular diseases.Mesangial cell-mediated
      glomerulonephritis is a frequent cause of kidney disease. Here the authors show
      that celastrol loaded in albumin nanoparticles efficiently targets mesangial
      cells, and is effective in rat models.

PMID- 29026084
TI  - Binary temporal upconversion codes of Mn2+-activated nanoparticles for multilevel
      anti-counterfeiting.
AB  - Optical characteristics of luminescent materials, such as emission profile and
      lifetime, play an important role in their applications in optical data storage,
      document security, diagnostics, and therapeutics. Lanthanide-doped upconversion
      nanoparticles are particularly suitable for such applications due to their
      inherent optical properties, including large anti-Stokes shift, distinguishable
      spectroscopic fingerprint, and long luminescence lifetime. However, conventional
      upconversion nanoparticles have a limited capacity for information storage or
      complexity to prevent counterfeiting. Here, we demonstrate that integration of
      long-lived Mn2+ upconversion emission and relatively short-lived lanthanide
      upconversion emission in a particulate platform allows the generation of binary
      temporal codes for efficient data encoding. Precise control of the particle's
      structure allows the excitation feasible both under 980 and 808 nm irradiation.
      We find that the as-prepared Mn2+-doped nanoparticles are especially useful for
      multilevel anti-counterfeiting with high-throughput rate of authentication and
      without the need for complex time-gated decoding instrumentation.Luminescent
      materials that are capable of binary temporal coding are desirable for multilevel
      anti-counterfeiting. Here, the authors engineer nanoparticles that produce binary
      color codes on different timescales by combining the long-lived luminescence of
      Mn2+ with the relatively short-lived emission of lanthanides.

PMID- 29026085
TI  - EZH2 enables germinal centre formation through epigenetic silencing of CDKN1A and
      an Rb-E2F1 feedback loop.
AB  - The EZH2 histone methyltransferase is required for B cells to form germinal
      centers (GC). Here we show that EZH2 mediates GC formation through repression of
      cyclin-dependent kinase inhibitor CDKN1A (p21Cip1). Deletion of Cdkn1a rescues
      the GC reaction in Ezh2 -/- mice. Using a 3D B cell follicular organoid system
      that mimics the GC reaction, we show that depletion of EZH2 suppresses G1 to S
      phase transition of GC B cells in a Cdkn1a-dependent manner. GC B cells of Cdkn1a
      -/- Ezh2 -/- mice have high levels of phospho-Rb, indicating that loss of Cdkn1a
      enables progression of cell cycle. Moreover, the transcription factor E2F1
      induces EZH2 during the GC reaction. E2f1 -/- mice manifest impaired GC
      responses, which is rescued by restoring EZH2 expression, thus defining a
      positive feedback loop in which EZH2 controls GC B cell proliferation by
      suppressing CDKN1A, enabling cell cycle progression with a concomitant
      phosphorylation of Rb and release of E2F1.The histone methyltransferase EZH2
      silences genes by generating H3K27me3 marks. Here the authors use a 3D GC
      organoid and show EZH2 mediates germinal centre (GC) formation through epigenetic
      silencing of CDKN1A and release of cell cycle checkpoints.

PMID- 29026086
TI  - Picosecond orientational dynamics of water in living cells.
AB  - Cells are extremely crowded, and a central question in biology is how this
      affects the intracellular water. Here, we use ultrafast vibrational spectroscopy
      and dielectric-relaxation spectroscopy to observe the random orientational motion
      of water molecules inside living cells of three prototypical organisms:
      Escherichia coli, Saccharomyces cerevisiae (yeast), and spores of Bacillus
      subtilis. In all three organisms, most of the intracellular water exhibits the
      same random orientational motion as neat water (characteristic time constants ~9
      and ~2 ps for the first-order and second-order orientational correlation
      functions), whereas a smaller fraction exhibits slower orientational dynamics.
      The fraction of slow intracellular water varies between organisms, ranging from
      ~20% in E. coli to ~45% in B. subtilis spores. Comparison with the water dynamics
      observed in solutions mimicking the chemical composition of (parts of) the
      cytosol shows that the slow water is bound mostly to proteins, and to a lesser
      extent to other biomolecules and ions.The cytoplasm's crowdedness leads one to
      expect that cell water is different from bulk water. By measuring the rotational
      motion of water molecules in living cells, Tros et al. find that apart from a
      small fraction of water solvating biomolecules, cell water has the same dynamics
      as bulk water.

PMID- 29026087
TI  - Ultra-strong nonlinear optical processes and trigonal warping in MoS2 layers.
AB  - Nonlinear optical processes, such as harmonic generation, are of great interest
      for various applications, e.g., microscopy, therapy, and frequency conversion.
      However, high-order harmonic conversion is typically much less efficient than low
      order, due to the weak intrinsic response of the higher-order nonlinear
      processes. Here we report ultra-strong optical nonlinearities in monolayer MoS2
      (1L-MoS2): the third harmonic is 30 times stronger than the second, and the
      fourth is comparable to the second. The third harmonic generation efficiency for
      1L-MoS2 is approximately three times higher than that for graphene, which was
      reported to have a large chi (3). We explain this by calculating the nonlinear
      response functions of 1L-MoS2 with a continuum-model Hamiltonian and quantum
      mechanical diagrammatic perturbation theory, highlighting the role of trigonal
      warping. A similar effect is expected in all other transition-metal
      dichalcogenides. Our results pave the way for efficient harmonic generation based
      on layered materials for applications such as microscopy and imaging.Harmonic
      generation is a nonlinear optical process occurring in a variety of materials;
      the higher orders generation is generally less efficient than lower orders. Here,
      the authors report that the third-harmonic is thirty times stronger than the
      second-harmonic in monolayer MoS2.

PMID- 29026090
TI  - Erratum: Observation of ultrahigh mobility surface states in a topological
      crystalline insulator by infrared spectroscopy.
AB  - A correction to this article has been published and is linked from the HTML
      version of this article.

PMID- 29026088
TI  - Characteristic rotational behaviors of rod-shaped cargo revealed by automated
      five-dimensional single particle tracking.
AB  - We report an automated single particle tracking technique for tracking the x, y,
      z coordinates, azimuthal and elevation angles of anisotropic plasmonic gold
      nanorod probes in live cells. These five spatial coordinates are collectively
      referred to as 5D. This method overcomes a long-standing challenge in
      distinguishing rotational motions from translational motions in the z-axis in
      differential interference contrast microscopy to result in full disclosure of
      nanoscale motions with high accuracy. Transferrin-coated endocytic gold nanorod
      cargoes initially undergo active rotational diffusion and display characteristic
      rotational motions on the membrane. Then as the cargoes being enclosed in
      clathrin-coated pits, they slow down the active rotation and experience a quiet
      period before they restore active rotational diffusion after fission and
      eventually being transported away from the original entry spots. Finally, the 3D
      trajectories and the accompanying rotational motions of the cargoes are resolved
      accurately to render the intracellular transport process in live
      cells.Distinguishing rotational motions from translational motions in the z-axis
      has been a long-standing challenge. Here the authors develop a five-dimensional
      single particle tracking method to detect rotational behaviors of nanocargos
      during clathrin-mediated endocytosis and intracellular transport.

PMID- 29026092
TI  - Response of microbial biomass and CO2-C loss to wetting patterns are temperature
      dependent in a semi-arid soil.
AB  - One of the greatest contemporary challenges in terrestrial ecology is to
      determine the impact of climate change on the world's ecosystems. Here we
      investigated how wetting patterns (frequency and intensity) and nutrient
      additions altered microbial biomass and CO2-C loss from a semi-arid soil. South
      western Australia is predicted to experience declining annual rainfall but
      increased frequency of summer rainfall events when soil is fallow. Agricultural
      soils (0-10 cm at 10  degrees C or 25  degrees C) received the same total amount
      of water (15 mL over 30 days) applied at different frequency; with either nil or
      added nitrogen and phosphorus. Smaller more frequent wetting applications
      resulted in less CO2-C loss (P < 0.001); with cumulative CO2-C loss 35% lower
      than a single wetting event. This coincided with increased microbial biomass C at
      25  degrees C but a decline at 10  degrees C. Increasing nutrient availability
      decreased CO2-C loss only under a single larger wetting event. While bacterial
      and fungal abundance remained unchanged, archaeal abundance and laccase-like
      copper monooxidase gene abundance increased with more frequent wetting at 25 
      degrees C. Our findings suggest smaller more frequent summer rainfall may
      decrease CO2 emissions compared to infrequent larger events; and enhance
      microbial C use efficiency where sufficient background soil organic matter and
      nutrients are available.

PMID- 29026091
TI  - Observation of Contrary Thermo-responsive Trend for Single Crystal and Powder
      Samples in Mechano-, Thermo- and Solvato-responsive Luminescent Cubane [Ag4I4L4]
      Cluster.
AB  - A new silver(I) iodide cluster [Ag4I4(TMP)4] (TMP = tris(3-methylphenyl)
      phosphine) 1 shows triply stimuli-responsive luminescent chromism, namely,
      mechano-, thermo- and solvent-responsive chromism, which is isostructural to our
      previously reported [Cu4I4(TMP)4] 2 but shows quite different luminescence in
      response to the external stimuli. Especially, during the mechanical grinding, the
      relative intensities of HE and LE of 1 varied with a concomitant hypsochromic
      shift, and when the temperature was decreased from 300 to 5 K, unprecedented
      contrary thermo-responsive trend for single crystal and powered samples
      (blueshift of single crystals and redshift of powdered samples) was observed.
      These distinct characters of 1 should be due to the different molecular packing
      modes, metallic interactions and the unique character of Ag(I) ion.

PMID- 29026093
TI  - Crystal structure of the flexible tandem repeat domain of bacterial cellulose
      synthesis subunit C.
AB  - Bacterial cellulose (BC) is synthesized and exported through the cell membrane
      via a large protein complex (terminal complex) that consists of three or four
      subunits. BcsC is a little-studied subunit considered to export BC to the
      extracellular matrix. It is predicted to have two domains: a tetratrico peptide
      repeat (TPR) domain and a beta-barrelled outer membrane domain. Here we report
      the crystal structure of the N-terminal part of BcsC-TPR domain (Asp24-Arg272)
      derived from Enterobacter CJF-002. Unlike most TPR-containing proteins which have
      continuous TPR motifs, this structure has an extra alpha-helix between two
      clusters of TPR motifs. Five independent molecules in the crystal had three
      different conformations that varied at the hinge of the inserted alpha-helix.
      Such structural feature indicates that the inserted alpha-helix confers
      flexibility to the chain and changes the direction of the TPR super-helix, which
      was also suggested by structural analysis of BcsC-TPR (Asp24-Leu664) in solution
      by size exclusion chromatography-small-angle X-ray scattering. The flexibility at
      the alpha-helical hinge may play important role for exporting glucan chains.

PMID- 29026094
TI  - Electropermeabilization of Inner and Outer Cell Membranes with Microsecond Pulsed
      Electric Fields: Quantitative Study with Calcium Ions.
AB  - Microsecond pulsed electric fields (MUsPEF) permeabilize the plasma membrane (PM)
      and are widely used in research, medicine and biotechnology. For internal
      membranes permeabilization, nanosecond pulsed electric fields (nsPEF) are applied
      but this technology is complex to use. Here we report that the endoplasmic
      reticulum (ER) membrane can also be electropermeabilized by one 100 us pulse
      without affecting the cell viability. Indeed, using Ca2+ as a permeabilization
      marker, we observed cytosolic Ca2+ peaks in two different cell types after one
      100 us pulse in a medium without Ca2+. Thapsigargin abolished these Ca2+ peaks
      demonstrating that the calcium is released from the ER. Moreover, IP3R and RyR
      inhibitors did not modify these peaks showing that they are due to the
      electropermeabilization of the ER membrane and not to ER Ca2+ channels
      activation. Finally, the comparison of the two cell types suggests that the PM
      and the ER permeabilization thresholds are affected by the sizes of the cell and
      the ER. In conclusion, this study demonstrates that usPEF, which are easier to
      control than nsPEF, can permeabilize internal membranes. Besides, MUsPEF
      interaction with either the PM or ER, can be an efficient tool to modulate the
      cytosolic calcium concentration and study Ca2+ roles in cell physiology.

PMID- 29026095
TI  - Alterations of regional homogeneity and functional connectivity in pituitary
      adenoma patients with visual impairment.
AB  - Evidences have showed that the deprivation of vision can considerably alter the
      resting-state activity both within and beyond the visual cortices. However, the
      functional changes of the brain cortices related to partially vision-deprivation
      are still largely unknown. Using resting-state functional MR imaging, we
      quantitatively evaluated the regional homogeneity(ReHo) and functional
      connectivity(FC) changes between 25 pituitary adenoma patients with visual
      impairment and 25 healthy controls(HCs). Compared with HCs, PAs exhibited
      significant increased ReHo in the left superior occipital gyrus, bilateral middle
      occipital gyrus and reduced ReHo in the left inferior frontal gyrus and right
      middle temporal gyrus. PAs also showed decreased FC between vision-related area
      and higher-order cognitive brain areas. Furthermore, we identified that in the
      PAs group the FC between the left V1 and left V3 increased while the FC between
      left V2v and left V5 significantly decreased, the FC between left V4 area and the
      V3, V2d area increased. In our study, we identified that the ReHo and FC were
      altered between the vision-related cortices and other higher-order cognitive
      cortices along with disorganized functional connectivity within the visual system
      in PAs with visual impairment. These findings may provide important insights to
      understand the plasticity of visual network.

PMID- 29026096
TI  - Plane of nutrition affects the phylogenetic diversity and relative abundance of
      transcriptionally active methanogens in the bovine rumen.
AB  - Methane generated during enteric fermentation in ruminant livestock species is a
      major contributor to global anthropogenic greenhouse gas emissions. A period of
      moderate feed restriction followed by ad libitum access to feed is widely applied
      in cattle management to exploit the animal's compensatory growth potential and
      reduce feed costs. In the present study, we utilised microbial RNA from rumen
      digesta samples to assess the phylogenetic diversity of transcriptionally active
      methanogens from feed-restricted and non-restricted animals. To determine the
      contribution of different rumen methanogens to methanogenesis during dietary
      restriction of cattle, we conducted high-throughput mcrA cDNA amplicon sequencing
      on an Illumina MiSeq and analysed both the abundance and phylogenetic origin of
      different mcrA cDNA sequences. When compared to their unrestricted
      contemporaries, in feed-restricted animals, the methanogenic activity, based on
      mcrA transcript abundance, of Methanobrevibacter gottschalkii clade increased
      while the methanogenic activity of the Methanobrevibacter ruminantium clade and
      members of the Methanomassiliicoccaceae family decreased. This study shows that
      the quantity of feed consumed can evoke large effects on the composition of
      methanogenically active species in the rumen of cattle. These data potentially
      have major implications for targeted CH4 mitigation approaches such as anti
      methanogen vaccines and/or tailored dietary management.

PMID- 29026089
TI  - A large scale hearing loss screen reveals an extensive unexplored genetic
      landscape for auditory dysfunction.
AB  - The developmental and physiological complexity of the auditory system is likely
      reflected in the underlying set of genes involved in auditory function. In
      humans, over 150 non-syndromic loci have been identified, and there are more than
      400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic
      hearing loss genes have been identified in mouse and human, but we remain
      ignorant of the full extent of the genetic landscape involved in auditory
      dysfunction. As part of the International Mouse Phenotyping Consortium, we
      undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In
      total, we identify 67 candidate hearing loss genes. We detect known hearing loss
      genes, but the vast majority, 52, of the candidate genes were novel. Our analysis
      reveals a large and unexplored genetic landscape involved with auditory
      function.The full extent of the genetic basis for hearing impairment is unknown.
      Here, as part of the International Mouse Phenotyping Consortium, the authors
      perform a hearing loss screen in 3006 mouse knockout strains and identify 52 new
      candidate genes for genetic hearing loss.

PMID- 29026098
TI  - HLA and Histo-Blood Group Antigen Expression in Human Pluripotent Stem Cells and
      their Derivatives.
AB  - One prerequisite for a successful clinical outcome of human pluripotent stem cell
      (hPSC) based therapies is immune compatibility between grafted cells/tissue and
      recipient. This study explores immune determinants of human embryonic stem cell
      lines (hESC) and induced human pluripotent stem cell (hiPSC) lines and hepatocyte
      and cardiomyocyte-like cells derived from these cells. HLA class I was expressed
      on all pluripotent hPSC lines which upon differentiation into hepatocyte-like
      cells was considerably reduced in contrast to cardiomyocyte-like cells which
      retained class I antigens. No HLA class II antigens were found in the pluripotent
      or differentiated cells. Histo-blood group carbohydrate antigens SSEA-3/SSEA
      4/SSEA-5, Globo H, A, Lex/Ley and sialyl-lactotetra were expressed on all hPSC
      lines. Blood group AB(O)H antigen expression was in accordance with ABO genotype.
      Interestingly, only a subpopulation of A1O1 cells expressed A. During
      differentiation of hPSC, some histo-blood group antigens showed congruent
      alteration patterns while expression of other antigens differed between the cell
      lines. No systematic difference in the hPSC cell surface tissue antigen
      expression was detected. In conclusion, hPSC and their derivatives express cell
      surface antigens that may cause an immune rejection. Furthermore, tissue antigen
      expression must be established for each individual stem cell line prior to
      clinical application.

PMID- 29026099
TI  - Subcortical Facilitation of Behavioral Responses to Threat.
AB  - Behavioral responses to threat are critical to survival. Several cortical and
      subcortical brain regions respond selectively to threat. However, the relation of
      these neural responses and their underlying representations to behavior is
      unclear. We examined the contribution of lower-order subcortical representations
      to behavioral responses to threat in adult humans. In Experiments 1 and 2,
      participants viewed pairs of images presented to the same eye or to different
      eyes. We observed a monocular advantage, which indicates subcortical
      facilitation, for ancestral threats (snakes, spiders), but not for modern
      threats, positive images, or neutral images. In Experiment 3, we presented pairs
      of snakes or neutral images into the temporal or nasal hemifield. For snakes
      only, we observed a temporal hemifield advantage, which indicates facilitation by
      the retino-tectal subcortical pathway. These results advance the current
      understanding of processing of threat by adult humans by revealing the
      characteristics of behaviors driven by a lower-order neural mechanism that is
      specialized for the processing of ancestral threats. The results also contribute
      to ongoing debates concerning the biological generality of neural mechanisms for
      processing of complex, emotionally-relevant stimuli by providing evidence for
      conservation of lower-order neural mechanisms for processing of ancestral threats
      across both ontogeny and phylogeny.

PMID- 29026097
TI  - Chemosensing of honeybee parasite, Varroa destructor: Transcriptomic analysis.
AB  - Chemosensing is a primary sense in nature, however little is known about its
      mechanism in Chelicerata. As a model organism we used the mite Varroa destructor,
      a key parasite of honeybees. Here we describe a transcriptomic analysis of two
      physiological stages for the Varroa foreleg, the site of primary olfactory organ.
      The transcriptomic analysis revealed transcripts of chemosensory related genes
      belonging to several groups. These include Niemann-Pick disease protein, type C2
      (NPC2), gustatory receptors (GRs), ionotropic receptors (IRs), sensory neuron
      membrane proteins (SNMPs) and odorant binding proteins (OBP). However, no insect
      odorant receptors (ORs) and odorant co-receptors (ORcos) were found. In addition,
      we identified a homolog of the most ancient IR co-receptor, IR25a, in Varroa as
      well as in other members of Acari. High expression of this transcript in the
      mite's forelegs, while not detectable in the other pairs of legs, suggests a
      function for this IR25a-like in Varroa chemosensing.

PMID- 29026100
TI  - A new semi-supervised learning model combined with Cox and SP-AFT models in
      cancer survival analysis.
AB  - Gene selection is an attractive and important task in cancer survival analysis.
      Most existing supervised learning methods can only use the labeled biological
      data, while the censored data (weakly labeled data) far more than the labeled
      data are ignored in model building. Trying to utilize such information in the
      censored data, a semi-supervised learning framework (Cox-AFT model) combined with
      Cox proportional hazard (Cox) and accelerated failure time (AFT) model was used
      in cancer research, which has better performance than the single Cox or AFT
      model. This method, however, is easily affected by noise. To alleviate this
      problem, in this paper we combine the Cox-AFT model with self-paced learning
      (SPL) method to more effectively employ the information in the censored data in a
      self-learning way. SPL is a kind of reliable and stable learning mechanism, which
      is recently proposed for simulating the human learning process to help the AFT
      model automatically identify and include samples of high confidence into
      training, minimizing interference from high noise. Utilizing the SPL method
      produces two direct advantages: (1) The utilization of censored data is further
      promoted; (2) the noise delivered to the model is greatly decreased. The
      experimental results demonstrate the effectiveness of the proposed model compared
      to the traditional Cox-AFT model.

PMID- 29026102
TI  - Fast identification of the conduction-type of nanomaterials by field emission
      technique.
AB  - There are more or less dopants or defects existing in nanomaterials, so they
      usually have different conduct-types even for the same substrate. Therefore, fast
      identification of the conduction-type of nanomaterials is very essential for
      their practical application in functional nanodevices. Here we use the field
      emission (FE) technique to research nanomaterials and establish a generalized
      Schottky-Nordheim (SN) model, in which an important parameter lambda (the image
      potential factor) is first introduced to describe the effective image potential.
      By regarding lambda as the criterion, their energy-band structure can be
      identified: (a) lambda = 1: metal; (b) 0.5 < lambda < 1: n-type semiconductor;
      (c) 0 < lambda < 0.5: p-type semiconductor. Moreover, this method can be utilized
      to qualitatively evaluate the doping-degree for a given semiconductor. We test
      numerically and experimentally a group of nanomaterial emitters and all results
      agree with our theoretical results very well, which suggests that our method
      based on FE measurements should be an ideal and powerful tool to fast ascertain
      the conduction-type of nanomaterials.

PMID- 29026101
TI  - Heterozygous RFX6 protein truncating variants are associated with MODY with
      reduced penetrance.
AB  - Finding new causes of monogenic diabetes helps understand glycaemic regulation in
      humans. To find novel genetic causes of maturity-onset diabetes of the young
      (MODY), we sequenced MODY cases with unknown aetiology and compared variant
      frequencies to large public databases. From 36 European patients, we identify two
      probands with novel RFX6 heterozygous nonsense variants. RFX6 protein truncating
      variants are enriched in the MODY discovery cohort compared to the European
      control population within ExAC (odds ratio = 131, P = 1 * 10-4). We find similar
      results in non-Finnish European (n = 348, odds ratio = 43, P = 5 * 10-5) and
      Finnish (n = 80, odds ratio = 22, P = 1 * 10-6) replication cohorts. RFX6
      heterozygotes have reduced penetrance of diabetes compared to common HNF1A and
      HNF4A-MODY mutations (27, 70 and 55% at 25 years of age, respectively). The
      hyperglycaemia results from beta-cell dysfunction and is associated with lower
      fasting and stimulated gastric inhibitory polypeptide (GIP) levels. Our study
      demonstrates that heterozygous RFX6 protein truncating variants are associated
      with MODY with reduced penetrance.Maturity-onset diabetes of the young (MODY) is
      the most common subtype of familial diabetes. Here, Patel et al. use targeted DNA
      sequencing of MODY patients and large-scale publically available data to show
      that RFX6 heterozygous protein truncating variants cause reduced penetrance MODY.

PMID- 29026103
TI  - Erratum: Joining smallholder farmers' traditional knowledge with metric traits to
      select better varieties of Ethiopian wheat.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29026104
TI  - CETSA quantitatively verifies in vivo target engagement of novel RIPK1 inhibitors
      in various biospecimens.
AB  - The proof of target engagement (TE) is a key element for evaluating potential
      investment in drug development. The cellular thermal shift assay (CETSA) is
      expected to facilitate direct measurement of intracellular TE at all stages of
      drug development. However, there have been no reports of applying this technology
      to comprehensive animal and clinical studies. This report demonstrates that CETSA
      can not only quantitatively evaluate the drug-TE in mouse peripheral blood, but
      also confirm TE in animal tissues exemplified by using the receptor interacting
      protein 1 kinase (RIPK1) lead compound we have developed. Our established semi
      automated system allows evaluation of the structure-activity relationship using
      native RIPK1 in culture cell lines, and also enables estimation of drug occupancy
      ratio in mouse peripheral blood mononuclear cells. Moreover, optimized tissue
      homogenisation enables monitoring of the in vivo drug-TE in spleen and brain. Our
      results indicate that CETSA methodology will provide an efficient tool for
      preclinical and clinical drug development.

PMID- 29026105
TI  - MCPH1, mutated in primary microcephaly, is required for efficient chromosome
      alignment during mitosis.
AB  - MCPH1 gene, mutated in primary microcephaly, regulates cell progression into
      mitosis. While this role has been extensively investigated in the context of DNA
      damage, its function during unperturbed cell cycles has been given less
      attention. Here we have analyzed the dynamics of chromosome condensation and cell
      cycle progression in MCPH1 deficient cells under undamaging conditions. Our study
      demonstrates that chromosome condensation is uncoupled from cell cycle
      progression when MCPH1 function is lacking, resulting in cells that prematurely
      condense their chromosomes during mid G2-phase and delay decondensation at the
      completion of mitosis. However, mitosis onset occurs on schedule in MCPH1
      deficient cells. We also revealed active Cdk1 to be mandatory for the premature
      onset of chromosome condensation during G2 and the maintenance of the condensed
      state thereafter. Interestingly, a novel cellular phenotype was observed while
      monitoring cell cycle progression in cells lacking MCPH1 function. Specifically,
      completion of chromosome alignment at the metaphase plate was significantly
      delayed. This deficiency reveals that MCPH1 is required for efficient chromosome
      biorientation during mitosis.

PMID- 29026106
TI  - Crumpling-based soft metamaterials: the effects of sheet pore size and porosity.
AB  - Crumpled-based materials are relatively easy to fabricate and show robust
      mechanical properties for practical applications, including meta-biomaterials
      design aimed for improved tissue regeneration. For such requests, however, the
      structure needs to be porous. We introduce a crumpled holey thin sheet as a
      robust bio-metamaterial and measure the mechanical response of a crumpled holey
      thin Mylar sheet as a function of the hole size and hole area fraction. We also
      study the formation of patterns of crease lines and ridges. The area fraction
      largely dominated the crumpling mechanism. We also show, the crumpling exponents
      slightly increases with increasing the hole area fraction and the total perimeter
      of the holes. Finally, hole edges were found to limit and guide the propagation
      of crease lines and ridges.

PMID- 29026107
TI  - Achilles tendon compositional and structural properties are altered after
      unloading by botox.
AB  - Tendon function and homeostasis rely on external loading. This study investigates
      the biological mechanisms behind tendon biomechanical function and how the
      mechanical performance is affected by reduced daily loading. The Achilles tendons
      of 16 weeks old female Sprague Dawley rats (n = 40) were unloaded for 5 weeks by
      inducing muscle paralysis with botulinum toxin injections in the right
      gastrocnemius and soleus muscles. The contralateral side was used as control.
      After harvest, the tendons underwent biomechanical testing to assess
      viscoelasticity (n = 30 rats) and small angle X-ray scattering to determine the
      structural properties of the collagen fibrils (n = 10 rats). Fourier transform
      infrared spectroscopy and histological staining (n = 10 rats) were performed to
      investigate the collagen and proteoglycan content. The results show that the
      stiffness increased in unloaded tendons, together with an increased collagen
      content. Creep and axial alignment of the collagen fibers were reduced. Stress
      relaxation increased whereas hysteresis was reduced in response to unloading with
      botox treatment. Our findings indicate that altered matrix deposition relies on
      mechanical loading to reorganize the newly formed tissue, without which the
      viscoelastic behavior is impaired. The results demonstrate that reduced daily
      loading deprives tendons of their viscoelastic properties, which could increase
      the risk of injury.

PMID- 29026108
TI  - RIFS: a randomly restarted incremental feature selection algorithm.
AB  - The advent of big data era has imposed both running time and learning efficiency
      challenges for the machine learning researchers. Biomedical OMIC research is one
      of these big data areas and has changed the biomedical research drastically. But
      the high cost of data production and difficulty in participant recruitment
      introduce the paradigm of "large p small n" into the biomedical research. Feature
      selection is usually employed to reduce the high number of biomedical features,
      so that a stable data-independent classification or regression model may be
      achieved. This study randomly changes the first element of the widely-used
      incremental feature selection (IFS) strategy and selects the best feature subset
      that may be ranked low by the statistical association evaluation algorithms, e.g.
      t-test. The hypothesis is that two low-ranked features may be orchestrated to
      achieve a good classification performance. The proposed Randomly re-started
      Incremental Feature Selection (RIFS) algorithm demonstrates both higher
      classification accuracy and smaller feature number than the existing algorithms.
      RIFS also outperforms the existing methylomic diagnosis model for the prostate
      malignancy with a larger accuracy and a lower number of transcriptomic features.

PMID- 29026109
TI  - Heterogeneous integration for on-chip quantum photonic circuits with single
      quantum dot devices.
AB  - Single-quantum emitters are an important resource for photonic quantum
      technologies, constituting building blocks for single-photon sources, stationary
      qubits, and deterministic quantum gates. Robust implementation of such functions
      is achieved through systems that provide both strong light-matter interactions
      and a low-loss interface between emitters and optical fields. Existing platforms
      providing such functionality at the single-node level present steep scalability
      challenges. Here, we develop a heterogeneous photonic integration platform that
      provides such capabilities in a scalable on-chip implementation, allowing direct
      integration of GaAs waveguides and cavities containing self-assembled InAs/GaAs
      quantum dots-a mature class of solid-state quantum emitter-with low-loss Si3N4
      waveguides. We demonstrate a highly efficient optical interface between Si3N4
      waveguides and single-quantum dots in GaAs geometries, with performance
      approaching that of devices optimized for each material individually. This
      includes quantum dot radiative rate enhancement in microcavities, and a path for
      reaching the non-perturbative strong-coupling regime.Effective use of single
      emitters in quantum photonics requires coherent emission, strong light-matter
      coupling, low losses and scalable fabrication. Here, Davanco et al. stride toward
      this goal by hybrid on-chip integration of Si3N4 waveguides and GaAs nanophotonic
      geometries with InAs quantum dots.

PMID- 29026110
TI  - A novel true random number generator based on a stochastic diffusive memristor.
AB  - The intrinsic variability of switching behavior in memristors has been a major
      obstacle to their adoption as the next generation of universal memory. On the
      other hand, this natural stochasticity can be valuable for hardware security
      applications. Here we propose and demonstrate a novel true random number
      generator utilizing the stochastic delay time of threshold switching in a Ag:SiO2
      diffusive memristor, which exhibits evident advantages in scalability, circuit
      complexity, and power consumption. The random bits generated by the diffusive
      memristor true random number generator pass all 15 NIST randomness tests without
      any post-processing, a first for memristive-switching true random number
      generators. Based on nanoparticle dynamic simulation and analytical estimates, we
      attribute the stochasticity in delay time to the probabilistic process by which
      Ag particles detach from a Ag reservoir. This work paves the way for memristors
      in hardware security applications for the era of the Internet of
      Things.Memristors can switch between high and low electrical-resistance states,
      but the switching behaviour can be unpredictable. Here, the authors harness this
      unpredictability to develop a memristor-based true random number generator that
      uses the stochastic delay time of threshold switching.

PMID- 29026111
TI  - Distraction and Expressive Suppression Strategies in Regulation of High- and Low
      Intensity Negative Emotions.
AB  - The current study compared the effectiveness of distraction, an antecedent
      focused strategy that involves diverting an individual's attention away from
      affective terms, and expressive suppression, a response-focused strategy that
      involves inhibiting conscious emotion-expressive behavior during an emotionally
      aroused state, in the regulation of high- and low-intensity unpleasant stimuli,
      using event-related potentials (ERPs). Sixteen participants completed an emotion
      regulation experiment in which they passively viewed high- or low-intensity
      unpleasant images (view), solved a mathematical equation presented on high- or
      low-intensity negative images (distraction), or suppressed their emotional
      expression in response to high- or low-intensity unpleasant images (suppression).
      Their negative experiences after implementation of these strategies were rated by
      participants on a 1-9 scale. We mainly found that compared with expressive
      suppression, distraction yielded greater attenuation of the early phase of centro
      parietal LPP when the participants responded to high-intensity stimuli. In the
      low-intensity condition, distraction, but not expressive suppression, effectively
      decreased the early phase of LPP. The findings suggest that expressive
      suppression works as early as distraction in the high-intensity condition; more
      importantly, distraction is superior to expressive suppression in regulating
      negative emotion, which is influenced by emotional intensity.

PMID- 29026112
TI  - Engineering species-like barriers to sexual reproduction.
AB  - Controlling the exchange of genetic information between sexually reproducing
      populations has applications in agriculture, eradication of disease vectors,
      control of invasive species, and the safe study of emerging biotechnology
      applications. Here we introduce an approach to engineer a genetic barrier to
      sexual reproduction between otherwise compatible populations. Programmable
      transcription factors drive lethal gene expression in hybrid offspring following
      undesired mating events. As a proof of concept, we target the ACT1 promoter of
      the model organism Saccharomyces cerevisiae using a dCas9-based transcriptional
      activator. Lethal overexpression of actin results from mating this engineered
      strain with a strain containing the wild-type ACT1 promoter.Genetic isolation of
      a genetically modified organism represents a useful strategy for biocontainment.
      Here the authors use dCas9-VP64-driven gene expression to construct a 'species
      like' barrier to reproduction between two otherwise compatible populations.

PMID- 29026113
TI  - Highly efficient cellular cloning using Ferro-core Micropallet Arrays.
AB  - Advancing knowledge of biological mechanisms has come to depend upon genetic
      manipulation of cells and organisms, relying upon cellular cloning methods that
      remain unchanged for decades, are labor and time intensive, often taking many
      months to come to fruition. Thus, there is a pressing need for more efficient
      processes. We have adapted a newly developed micropallet array platform, termed
      the "ferro-core micropallet array", to dramatically improve and accelerate the
      process of isolating clonal populations of adherent cells from heterogeneous
      mixtures retaining the flexibility of employing a wide range of cytometric
      parameters for identifying colonies and cells of interest. Using transfected
      (retroviral oncogene or fluorescent reporter construct) rat 208 F cells, we
      demonstrated the capacity to isolate and expand pure populations of genetically
      manipulated cells via laser release and magnetic recovery of single micropallets
      carrying adherent microcolonies derived from single cells. This platform can be
      broadly applied to biological research, across the spectrum of molecular biology
      to cellular biology, involving fields such as cancer, developmental, and stem
      cell biology. The ferro-core micropallet array platform provides significant
      advantages over alternative sorting and cloning methods by eliminating the
      necessity for repetitive purification steps and increasing throughput by
      dramatically shortening the time to obtain clonally expanded cell colonies.

PMID- 29026115
TI  - Visual sensory stimulation interferes with people's ability to echolocate object
      size.
AB  - Echolocation is the ability to use sound-echoes to infer spatial information
      about the environment. People can echolocate for example by making mouth clicks.
      Previous research suggests that echolocation in blind people activates brain
      areas that process light in sighted people. Research has also shown that
      echolocation in blind people may replace vision for calibration of external
      space. In the current study we investigated if echolocation may also draw on
      'visual' resources in the sighted brain. To this end, we paired a sensory
      interference paradigm with an echolocation task. We found that exposure to an
      uninformative visual stimulus (i.e. white light) while simultaneously
      echolocating significantly reduced participants' ability to accurately judge
      object size. In contrast, a tactile stimulus (i.e. vibration on the skin) did not
      lead to a significant change in performance (neither in sighted, nor blind echo
      expert participants). Furthermore, we found that the same visual stimulus did not
      affect performance in auditory control tasks that required detection of changes
      in sound intensity, sound frequency or sound location. The results suggest that
      processing of visual and echo-acoustic information draw on common neural
      resources.

PMID- 29026114
TI  - The driver landscape of sporadic chordoma.
AB  - Chordoma is a malignant, often incurable bone tumour showing notochordal
      differentiation. Here, we defined the somatic driver landscape of 104 cases of
      sporadic chordoma. We reveal somatic duplications of the notochordal
      transcription factor brachyury (T) in up to 27% of cases. These variants
      recapitulate the rearrangement architecture of the pathogenic germline
      duplications of T that underlie familial chordoma. In addition, we find
      potentially clinically actionable PI3K signalling mutations in 16% of cases.
      Intriguingly, one of the most frequently altered genes, mutated exclusively by
      inactivating mutation, was LYST (10%), which may represent a novel cancer gene in
      chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the
      authors investigate driver mutations of sporadic chordoma in 104 cases, revealing
      duplications in notochordal transcription factor brachyury (T), PI3K signalling
      mutations, and mutations in LYST, a potential novel cancer gene in chordoma.

PMID- 29026116
TI  - The Value of lncRNA NEAT1 as a Prognostic Factor for Survival of Cancer Outcome:
      A Meta-Analysis.
AB  - The present meta-analysis aimed to analyze available data to identify the
      prognostic role of NEAT1 in multiple carcinomas. A systematic search was
      performed by using several computerized databases from inception to June 7, 2017.
      The quantity of the publications was assessed according to MOOSE checklist.
      Pooled HRs with 95% CI was calculated to summarize the effect. A total of 12
      studies with 3,262 cancer patients were pooled in the analysis to evaluate the
      prognostic value of NEAT1 in multiple tumors. High expression levels of NEAT1
      were demonstrated to be associated with poor OS (HR = 1.71, 95%CI: 1.37-2.14, P <
      0.001) and tumor progression (III/IV vs. I/II: HR 1.76, 95%CI: 1.40-2.21, P <
      0.00001). Subgroup analysis showed that NEAT1 detection method (qRT-PCR) and
      sample size (more or less than 100) did not alter the predictive value of NEAT1
      on OS in various cancers. According to the meta-regression results, the large
      heterogeneity of meta-analysis may be attributed to the differences of NEAT1
      detection method. Furthermore, elevated NEAT1 expression significantly predicted
      lymph node metastasis (HR: 2.10, 95%CI: 1.32-3.33, P = 0.002) and distant
      metastasis (HR: 2.80, 95%CI: 1.60-4.91, P = 0.0003) respectively. The results
      indicate that NEAT1 expression level is a prognostic biomarker for OS and
      metastasis in general tumors.

PMID- 29026117
TI  - Involvement of the accumbal osteopontin-interacting transmembrane protein 168 in
      methamphetamine-induced place preference and hyperlocomotion in mice.
AB  - Chronic exposure to methamphetamine causes adaptive changes in brain, which
      underlie dependence symptoms. We have found that the transmembrane protein 168
      (TMEM168) is overexpressed in the nucleus accumbens of mice upon repeated
      methamphetamine administration. Here, we firstly demonstrate the inhibitory
      effect of TMEM168 on methamphetamine-induced behavioral changes in mice, and
      attempt to elucidate the mechanism of this inhibition. We overexpressed TMEM168
      in the nucleus accumbens of mice by using an adeno-associated virus vector (NAc
      TMEM mice). Methamphetamine-induced hyperlocomotion and conditioned place
      preference were attenuated in NAc-TMEM mice. Additionally, methamphetamine
      induced extracellular dopamine elevation was suppressed in the nucleus accumbens
      of NAc-TMEM mice. Next, we identified extracellular matrix protein osteopontin as
      an interacting partner of TMEM168, by conducting immunoprecipitation in cultured
      COS-7 cells. TMEM168 overexpression in COS-7 cells induced the enhancement of
      extracellular and intracellular osteopontin. Similarly, osteopontin enhancement
      was also observed in the nucleus accumbens of NAc-TMEM mice, in in vivo studies.
      Furthermore, the infusion of osteopontin proteins into the nucleus accumbens of
      mice was found to inhibit methamphetamine-induced hyperlocomotion and conditioned
      place preference. Our studies suggest that the TMEM168-regulated osteopontin
      system is a novel target pathway for the therapy of methamphetamine dependence,
      via regulating the dopaminergic function in the nucleus accumbens.

PMID- 29026118
TI  - Coherent coupling between Vanadyl Phthalocyanine spin ensemble and microwave
      photons: towards integration of molecular spin qubits into quantum circuits.
AB  - Electron spins are ideal two-level systems that may couple with microwave photons
      so that, under specific conditions, coherent spin-photon states can be realized.
      This represents a fundamental step for the transfer and the manipulation of
      quantum information. Along with spin impurities in solids, molecular spins in
      concentrated phases have recently shown coherent dynamics under microwave
      stimuli. Here we show that it is possible to obtain high cooperativity regime
      between a molecular Vanadyl Phthalocyanine (VOPc) spin ensemble and a high
      quality factor superconducting YBa2Cu3O7 (YBCO) coplanar resonator at 0.5 K. This
      demonstrates that molecular spin centers can be successfully integrated in hybrid
      quantum devices.

PMID- 29026119
TI  - Evaluating the importance of metamorphism in the foundering of continental crust.
AB  - The metamorphic conditions and mechanisms required to induce foundering in deep
      arc crust are assessed using an example of representative lower crust in SW New
      Zealand. Composite plutons of Cretaceous monzodiorite and gabbro were emplaced at
      ~1.2 and 1.8 GPa are parts of the Western Fiordland Orthogneiss (WFO); examples
      of the plutons are tectonically juxtaposed along a structure that excised ~25 km
      of crust. The 1.8 GPa Breaksea Orthogneiss includes suitably dense minor
      components (e.g. eclogite) capable of foundering at peak conditions. As the
      eclogite facies boundary has a positive dP/dT, cooling from supra-solidus
      conditions (T > 950 oC) at high-P should be accompanied by omphacite and garnet
      growth. However, a high monzodioritic proportion and inefficient metamorphism in
      the Breaksea Orthogneiss resulted in its positive buoyancy and preservation.
      Metamorphic inefficiency and compositional relationships in the 1.2 GPa Malaspina
      Pluton meant it was never likely to have developed densities sufficiently high to
      founder. These relationships suggest that the deep arc crust must have primarily
      involved significant igneous accumulation of garnet-clinopyroxene (in proportions
      >75%). Crustal dismemberment with or without the development of extensional shear
      zones is proposed to have induced foundering of excised cumulate material at P >
      1.2 GPa.

PMID- 29026120
TI  - Co-inoculum of Beauveria brongniartii and B. bassiana shows in vitro different
      metabolic behaviour in comparison to single inoculums.
AB  - The use of entomopathogenic fungi for biocontrol of plant pests is recently
      receiving an increased interest due to the need of reducing the impact of
      agricultural practices on the environment. Biocontrol efficacy could be improved
      by co-inoculation of different microorganisms. However, interactions between the
      fungal species can trigger or depress the biocontrol activity. Co-inoculation of
      two entomopathogenic fungi (Beauveria bassiana and B. brongniartii) was performed
      in vitro to evaluate the effects of their joint behaviour on a range of different
      carbon sources in comparison to single inoculation. The two species showed a very
      different metabolic profile by Phenotype MicroArrayTM. B. bassiana showed a
      broader metabolism than B. brongniartii on a range of substrates. B. brongniartii
      showed a greater specificity in substrate utilization. Several carbon sources (L
      Asparagine, L-Aspartic Acid, L- Glutamic Acid, m- Erythritol, D-Melezitose, D
      Sorbitol) triggered the fungal metabolism in the co-inoculum. SSR markers and
      Real Time qPCR analysis showed that different substrates promoted either the
      growth of one or the other species, suggesting a form of interaction between the
      two fungi, related to their different ecological niches. The methodological
      approach that combines Phenotype MicroArrayTM and SSR genotyping appeared useful
      to assess the performance and potential competition of co-inoculated
      entomopathogenic fungi.

PMID- 29026121
TI  - White noise enhances new-word learning in healthy adults.
AB  - Research suggests that listening to white noise may improve some aspects of
      cognitive performance in individuals with lower attention. This study
      investigated the impact of white noise on new word learning in healthy young
      adults, and whether this effect was mediated by executive attention skills.
      Eighty participants completed a single training session to learn the names of
      twenty novel objects. The session comprised 5 learning phases, each followed by a
      recall test. A final recognition test was also administered. Half the
      participants listened to white noise during the learning phases, and half
      completed the learning in silence. The noise group demonstrated superior recall
      accuracy over time, which was not impacted by participant attentional capacity.
      Recognition accuracy was near ceiling for both groups. These findings suggest
      that white noise has the capacity to enhance lexical acquisition.

PMID- 29026122
TI  - Nanoparticulate vacuolar ATPase blocker exhibits potent host-targeted antiviral
      activity against feline coronavirus.
AB  - Feline infectious peritonitis (FIP), caused by a mutated feline coronavirus, is
      one of the most serious and fatal viral diseases in cats. The disease remains
      incurable, and there is no effective vaccine available. In light of the
      pathogenic mechanism of feline coronavirus that relies on endosomal acidification
      for cytoplasmic entry, a novel vacuolar ATPase blocker, diphyllin, and its
      nanoformulation are herein investigated for their antiviral activity against the
      type II feline infectious peritonitis virus (FIPV). Experimental results show
      that diphyllin dose-dependently inhibits endosomal acidification in fcwf-4 cells,
      alters the cellular susceptibility to FIPV, and inhibits the downstream virus
      replication. In addition, diphyllin delivered by polymeric nanoparticles
      consisting of poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA)
      further demonstrates an improved safety profile and enhanced inhibitory activity
      against FIPV. In an in vitro model of antibody-dependent enhancement of FIPV
      infection, diphyllin nanoparticles showed a prominent antiviral effect against
      the feline coronavirus. In addition, the diphyllin nanoparticles were well
      tolerated in mice following high-dose intravenous administration. This study
      highlights the therapeutic potential of diphyllin and its nanoformulation for the
      treatment of FIP.

PMID- 29026124
TI  - A Unified Framework for Modeling Continuum and Rarefied Gas Flows.
AB  - The momentum and heat transport in rarefied gas flows is known to deviate from
      the classical laws of Navier and Fourier in Navier-Stokes-Fourier (NSF)
      equations. A more sophisticated Nonlinear Coupled Constitutive Model (NCCM) has
      been derived from the Boltzmann equation to describe gaseous and thermal
      transport both in continuum and rarefied gas flows. We first develop a unified
      numerical framework for modeling continuum and rarefied flows based on the NCCM
      model both in two and three dimensions. Special treatment is given to the complex
      highly nonlinear transport equations for non-conserved variables that arise from
      the high degree of thermal nonequilibrium. For verification and validation, we
      apply the present scheme to a stiff problem of hypersonic gas flows around a 2D
      cylinder, a 3D sphere, and the Apollo configuration both in continuum and
      rarefied situations. The results show that the present unified framework yields
      solutions that are in better agreement with the benchmark and experimental data
      than are the NSF results in all studied cases of rarefied problems. Good
      agreement is observed between the present study and the NSF results for continuum
      cases. The results show that this study provides a unified framework for modeling
      continuum and rarefied gas flows.

PMID- 29026123
TI  - Music induced happy mood suppresses the neural responses to other's pain:
      Evidences from an ERP study.
AB  - In the current study, we explored the time course of processing other's pain
      under induced happy or sad moods. Event-related potentials (ERPs) were recorded
      when participants observing pictures showing others in painful or non-painful
      situations. Mood induction procedures were applied to the participants before the
      picture observation task. Happy and sad moods were induced by listening to about
      10 minutes of music excerpts selected from the Chinese Affective Music System
      (CAMS). The ERP results revealed that the induced mood can influence the early
      automatic components N1, P2, and N2 but not the later top-down controlled
      components P3 and LPP. The difference of amplitudes elicited by painful and non
      painful stimuli was significantly different only in a sad mood but not in a happy
      mood, which indicates that comparing to a sad mood, the participants' ability to
      discriminate the painful stimuli from the non-painful stimuli was weakened in a
      happy mood. However, this reduction of sensitivity to other's pain in a happy
      mood does not necessarily reduce the tendency of prosocial behaviors. These
      findings offer psychophysiological evidences that people's moods can influence
      their empathic response towards other's pain.

PMID- 29026126
TI  - Bielectron vortices in two-dimensional Dirac semimetals.
AB  - Searching for new states of matter and unusual quasi-particles in emerging
      materials and especially low-dimensional systems is one of the major trends in
      contemporary condensed matter physics. Dirac materials, which host quasi
      particles which are described by ultrarelativistic Dirac-like equations, are of a
      significant current interest from both a fundamental and applied physics
      perspective. Here we show that a pair of two-dimensional massless Dirac-Weyl
      fermions can form a bound state independently of the sign of the inter-particle
      interaction potential, as long as this potential decays at large distances faster
      than Kepler's inverse distance law. This leads to the emergence of a new type of
      energetically favorable quasiparticle: bielectron vortices, which are double
      charged and reside at zero-energy. Their bosonic nature allows for condensation
      and may give rise to Majorana physics without invoking a superconductor. These
      novel quasi-particles arguably explain a range of poorly understood experiments
      in gated graphene structures at low doping.Two-dimensional Dirac semimetals are
      known to host fermionic excitations which can mimic physics usually found in
      ultrarelativistic quantum mechanics. Here, the authors unveil the existence of
      another type of quasiparticle, bielectron vortices, which are bosonic and may
      give rise to new types of condensates.

PMID- 29026125
TI  - Cell density-dependent differential proliferation of neural stem cells on
      omnidirectional nanopore-arrayed surface.
AB  - Recently, the importance of surface nanotopography in the determination of stem
      cell fate and behavior has been revealed. In the current study, we generated
      polystyrene cell-culture dishes with an omnidirectional nanopore arrayed surface
      (ONAS) (diameter: 200 nm, depth: 500 nm, center-to-center distance: 500 nm) and
      investigated the effects of nanotopography on rat neural stem cells (NSCs). NSCs
      cultured on ONAS proliferated better than those on the flat surface when cell
      density was low and showed less spontaneous differentiation during proliferation
      in the presence of mitogens. Interestingly, NSCs cultured on ONAS at clonal
      density demonstrated a propensity to generate neurospheres, whereas those on the
      flat surface migrated out, proliferated as individuals, and spread out to attach
      to the surface. However, the differential patterns of proliferation were cell
      density-dependent since the distinct phenomena were lost when cell density was
      increased. ONAS modulated cytoskeletal reorganization and inhibited formation of
      focal adhesion, which is generally observed in NSCs grown on flat surfaces. ONAS
      appeared to reinforce NSC-NSC interaction, restricted individual cell migration
      and prohibited NSC attachment to the nanopore surface. These data demonstrate
      that ONAS maintains NSCs as undifferentiated while retaining multipotency and is
      a better topography for culturing low density NSCs.

PMID- 29026127
TI  - Controlled delivery and minimally invasive imaging of stem cells in the lung.
AB  - Intratracheal delivery of stem cells into injured or diseased lungs can provide a
      variety of therapeutic and immunomodulatory effects for the treatment of acute
      lung injury and chronic lung disease. While the efficacy of this approach depends
      on delivering the proper cell dosage into the target region of the airway,
      tracking and analysis of the cells have been challenging, largely due to the
      limited understanding of cell transport and lack of suitable cell monitoring
      techniques. We report on the transport and deposition of intratracheally
      delivered stem cells as well as strategies to modulate the number of cells (e.g.,
      dose), topographic distribution, and region-specific delivery in small (rodent)
      and large (porcine and human) lungs. We also developed minimally invasive imaging
      techniques for real-time monitoring of intratracheally delivered cells. We
      propose that this approach can facilitate the implementation of patient-specific
      cells and lead to enhanced clinical outcomes in the treatment of lung disease
      with cell-based therapies.

PMID- 29026128
TI  - Risk of malignancy in thyroid nodules: predictive value of puncture feeling of
      grittiness in the process of fine-needle aspiration.
AB  - Fine-needle aspiration cytology (FNAC) is widely used for diagnosing thyroid
      nodules. However, there has been no specific investigation about the puncture
      feeling of grittiness. The aim of the present study was to see if the puncture
      feeling of grittiness during fine-needle aspiration procedure, combined with
      standard FNAC, could improve the accuracy in diagnosing thyroid cancer. A total
      of one thousand five hundred and thirty-one thyroid FNAC specimens acquired
      between January 2013 and January 2017 were retrospectively retrieved. All cases
      underwent surgical intervention. The FNAC diagnoses and puncture feeling of
      grittiness were evaluated and compared with the results of final
      histopathological diagnoses. The sensitivity, specificity, positive predictive
      value (PPV) and negative predictive value (NPV) of diagnosis for thyroid nodules
      by FNAC alone, puncture feeling of grittiness alone, and the combination of FNAC
      plus grittiness were calculated respectively. The findings of our study suggest
      that puncture feeling of grittiness is a useful adjunct. Adding puncture feeling
      of grittiness to FNAC can significantly enhance the ability to differentiate
      malignant thyroid nodules from benign thyroid nodules. More importantly, we found
      that puncture feeling of grittiness is surprising trust-worthy in being near
      perfectly reproducible per individual radiologist, and among different operators.

PMID- 29026129
TI  - Hepatitis virus infection and age-related cataract.
AB  - This study was performed to investigate the relationships of hepatitis B (HBV)
      and hepatitis C virus (HCV) infection to age-related cataract, and to assess
      whether liver damage mediates the hepatitis-cataract association. This study
      analyzed data in the Korea National Health and Nutrition Examination Survey 2010
      2012 on 10,037 participants aged >=40 years. We performed mediation analysis to
      address the contribution of serum markers of liver damage, high aspartate (AST,
      >49.9 IU/L) and alanine aminotransferase (ALT, >56.1 IU/L), to the relationships
      of HBV and HCV infection to cataract. Odds ratios (ORs) for nuclear and any
      cataract with HBV infection were 1.09 [95% confidence interval (95CI) = 1.02
      1.16] and 1.07 (95CI = 1.00-1.14), respectively, compared to HBV uninfection; ORs
      with HCV infection were 1.35 (95CI = 1.18-1.55) and 1.40 (95CI = 1.12-1.76),
      respectively. High AST completely mediated the HBV infection-any cataract
      association. The significant relationships of HCV infection with nuclear and any
      cataract were formed only by their direct effects, not by mediation effects of
      high AST or ALT. HBV and HCV infection was significantly associated with nuclear
      and any cataract. High AST significantly mediates the effects of HBV infections
      on any cataract outcome, but the associations of HCV infection with nuclear and
      any cataract were not mediated by high AST or ALT.

PMID- 29026130
TI  - Effects of predator lipids on dinoflagellate defence mechanisms - increased
      bioluminescence capacity.
AB  - Short flashes of blue light (bioluminescence) from dinoflagellates can reduce
      copepod grazing of light-emitting cells. Other protective strategies against
      grazing are toxicity, reduced cell chain length and altered swimming patterns in
      different phytoplankton. Both toxicity and bioluminescence capacity in
      dinoflagellates decrease in copepod-free cultures, but toxin production can be
      restored in response to chemical alarm signals from copepods, copepodamides. Here
      we show that strains of the dinoflagellates Lingulodinium polyedra and
      Alexandrium tamarense, kept in culture for 14 and 9 years respectively, are
      capable of increasing their total bioluminescence capacity in response to
      copepodamides. The luminescence response to mechanical stimulation with air
      bubbles also increases significantly in L. polyedra after exposure to
      copepodamides. Effects on size, swimming speed and rate of change of direction in
      L. polyedra and A. tamarense were not detected, suggesting that post-encounter
      mechanisms such as bioluminescence and toxin production may constitute the
      dominating line of defence in these taxa. To our knowledge, this study provides
      the first evidence of changes in bioluminescence physiology as a response to
      chemical cues from natural enemies and emphasizes the importance of
      bioluminescence as an anti-grazing strategy.

PMID- 29026131
TI  - Mechanical stress induces elastic fibre disruption and cartilage matrix increase
      in ligamentum flavum.
AB  - Lumbar spinal stenosis (LSS) is one of the most frequent causes of low back pain
      and gait disturbance in the elderly. Ligamentum flavum (LF) hypertrophy is the
      main pathomechanism of LSS, but the reason for its occurrence is not clearly
      elucidated. In this study, we established a novel animal model of intervertebral
      mechanical stress concentration and investigated the biological property of the
      LF. The LF with mechanical stress concentration showed degeneration with elastic
      fibres disruption and cartilage matrix increase, which are similar to the
      findings in hypertrophied LF from patients with LSS. By contrast, decreased
      Col2a1 expression was found in the LF at fixed levels, in which mechanical stress
      was strongly reduced. These findings indicate that mechanical stress plays a
      crucial role in LF hypertrophy through cartilage matrix increase. The findings
      also suggest that fusion surgery, which eliminates intervertebral instability,
      may change the property of the LF and lead to the relief of patients' symptoms.

PMID- 29026133
TI  - Morphology and mechanics of fungal mycelium.
AB  - We study a unique biomaterial developed from fungal mycelium, the vegetative part
      and the root structure of fungi. Mycelium has a filamentous network structure
      with mechanics largely controlled by filament elasticity and branching, and
      network density. We report the morphological and mechanical characterization of
      mycelium through an integrated experimental and computational approach. The
      monotonic mechanical behavior of the mycelium is non-linear both in tension and
      compression. The material exhibits considerable strain hardening before rupture
      under tension, it mimics the open cell foam behavior under compression and
      exhibits hysteresis and the Mullins effect when subjected to cyclic loading.
      Based on our morphological characterization and experimental observations, we
      develop and validate a multiscale fiber network-based model for the mycelium
      which reproduces the tensile and compressive behavior of the material.

PMID- 29026132
TI  - Evidence of Early-Stage Selection on EPAS1 and GPR126 Genes in Andean High
      Altitude Populations.
AB  - The aim of this study is to identify genetic variants that harbour signatures of
      recent positive selection and may facilitate physiological adaptations to
      hypobaric hypoxia. To achieve this, we conducted whole genome sequencing and lung
      function tests in 19 Argentinean highlanders (>3500 m) comparing them to 16
      Native American lowlanders. We developed a new statistical procedure using a
      combination of population branch statistics (PBS) and number of segregating sites
      by length (nSL) to detect beneficial alleles that arose since the settlement of
      the Andes and are currently present in 15-50% of the population. We identified
      two missense variants as significant targets of selection. One of these variants,
      located within the GPR126 gene, has been previously associated with the forced
      expiratory volume/forced vital capacity ratio. The other novel missense variant
      mapped to the EPAS1 gene encoding the hypoxia inducible factor 2alpha. EPAS1 is
      known to be the major selection candidate gene in Tibetans. The derived allele of
      GPR126 is associated with lung function in our sample of highlanders (p < 0.05).
      These variants may contribute to the physiological adaptations to hypobaric
      hypoxia, possibly by altering lung function. The new statistical approach might
      be a useful tool to detect selected variants in population studies.

PMID- 29026134
TI  - MCT1 and MCT4 Expression and Lactate Flux Activity Increase During White and
      Brown Adipogenesis and Impact Adipocyte Metabolism.
AB  - Adipose tissue takes up glucose and releases lactate, thereby contributing
      significantly to systemic glucose and lactate homeostasis. This implies the
      necessity of upregulation of net acid and lactate flux capacity during adipocyte
      differentiation and function. However, the regulation of lactate- and acid/base
      transporters in adipocytes is poorly understood. Here, we tested the hypothesis
      that adipocyte thermogenesis, browning and differentiation are associated with an
      upregulation of plasma membrane lactate and acid/base transport capacity that in
      turn is important for adipocyte metabolism. The mRNA and protein levels of the
      lactate-H+ transporter MCT1 and the Na+,HCO3- cotransporter NBCe1 were
      upregulated in mouse interscapular brown and inguinal white adipose tissue upon
      cold induction of thermogenesis and browning. MCT1, MCT4, and NBCe1 were
      furthermore strongly upregulated at the mRNA and protein level upon
      differentiation of cultured pre-adipocytes. Adipocyte differentiation was
      accompanied by increased plasma membrane lactate flux capacity, which was reduced
      by MCT inhibition and by MCT1 knockdown. Finally, in differentiated brown
      adipocytes, glycolysis (assessed as ECAR), and after noradrenergic stimulation
      also oxidative metabolism (OCR), was decreased by MCT inhibition. We suggest that
      upregulation of MCT1- and MCT4-mediated lactate flux capacity and NBCe1-mediated
      HCO3-/pH homeostasis are important for the physiological function of mature
      adipocytes.

PMID- 29026135
TI  - Interventions for treating displaced intracapsular femoral neck fractures in the
      elderly: a Bayesian network meta-analysis of randomized controlled trials.
AB  - Displaced intracapsular femoral neck (AO type 31 B2/3) fractures have various
      treatments, including internal fixation (IF), unipolar uncemented
      hemiarthroplasty (HA), bipolar uncemented HA, unipolar cemented HA, bipolar
      cemented HA, uncemented total hip replacement (THR), and cemented THR. Systematic
      literature retrieval was performed from the databases to compare them in a
      network meta-analysis. Forty studies (85 arms) containing 6141 patients were
      included. Overall, our network meta-analysis rank the orders of 7 procedures in
      reoperation, mortality, dislocation and infection, which indicates that IF may
      provide the highest reoperation incidence, unipolar cemented HA may provide the
      lowest reoperation incidence; uncemented THR contributes the highest dislocation
      incidence; and bipolar uncemented HA provides the lowest infection incidence. No
      differences in mortality were observed among the treatments. This conclusion is
      indirect; higher-quality direct comparisons are required.

PMID- 29026136
TI  - Effective purifying selection in ancient asexual oribatid mites.
AB  - Sex is beneficial in the long term because it can prevent mutational meltdown
      through increased effectiveness of selection. This idea is supported by empirical
      evidence of deleterious mutation accumulation in species with a recent transition
      to asexuality. Here, we study the effectiveness of purifying selection in
      oribatid mites which have lost sex millions of years ago and diversified into
      different families and species while reproducing asexually. We compare the
      accumulation of deleterious nonsynonymous and synonymous mutations between three
      asexual and three sexual lineages using transcriptome data. Contrasting studies
      of young asexual lineages, we find evidence for strong purifying selection that
      is more effective in asexual as compared to sexual oribatid mite lineages. Our
      results suggest that large populations likely sustain effective purifying
      selection and facilitate the escape of mutational meltdown in the absence of sex.
      Thus, sex per se is not a prerequisite for the long-term persistence of animal
      lineages.Asexual reproduction is thought to be an evolutionary dead end in
      eukaryotes because deleterious mutations will not be purged effectively. Here,
      Brandt and colleagues show that anciently asexual oribatid mites in fact have
      reduced accumulation of deleterious mutations compared to their sexual relatives.

PMID- 29026138
TI  - Reproduction of an azooxanthellate coral is unaffected by ocean acidification.
AB  - Anthropogenic carbon dioxide (CO2) emissions and consequent ocean acidification
      (OA) are projected to have extensive consequences on marine calcifying organisms,
      including corals. While the effects of OA on coral calcification are well
      documented, the response of reproduction is still poorly understood since no
      information are reported for temperate corals. Here we investigate for the first
      time the influence of OA on sexual reproduction of the temperate azooxanthellate
      solitary scleractinian Leptopsammia pruvoti transplanted along a natural pCO2
      gradient at a Mediterranean CO2 vent. After 3 months, future projection of pH
      levels did not influence the germ cell production, gametogenesis and
      embryogenesis in this azooxanthellate coral. These findings suggest that
      reproductive potential may be quite tolerant to decreasing pH, with implications
      for ecosystem function and services in a changing ocean.

PMID- 29026137
TI  - Opiate use inhibits TLR9 signaling pathway in vivo: possible role in pathogenesis
      of HIV-1 infection.
AB  - The molecular mechanism of opiate use promoting HIV-1 infection is not fully
      understood. TLR9 is expressed in many immune cells, including monocytes,
      macrophages, which can recognize viruses and viral products and consequently
      induce the production of antiviral factors and initiate immune responses.
      Previous studies have shown that chronic viral infections can overcome and impair
      TLR9 pathway. We aimed to explore whether opiate use enhances HIV infection
      through inhibition of TLR9 pathway via a population-based study. A total of 200
      subjects were enrolled and divided into four groups as follows: Opiate+ HIV+
      (50), Opiate- HIV+ (50), Opiate+ HIV- (50), and healthy control (Opiate- HIV-,
      50). All HIV-infected subjects did not receive antiretroviral therapy while they
      were enrolled in the study. The results showed that opiate use was associated
      with higher viral load and lower CD4+ T cell count. Opiate use alone led to lower
      expression of TLR9, IRF7, and IFN-alpha at the protein level in PBMCs. Combined
      with HIV-1 infection, opiate use resulted in lower expression of MyD88, ISG56,
      and MxA. In addition, morphine treatment promoted HIV-1 replication in
      macrophages via inhibition of TLR9 pathway. Our data reveal that opiate use plays
      a cofactor role in pathogenesis of HIV-1 infection through inhibition of TLR9
      pathway.

PMID- 29026140
TI  - Embroidered Copper Microwire Current Collector for Improved Cycling Performance
      of Silicon Anodes in Lithium-Ion Batteries.
AB  - Si holds great promise as an alloying anode material for Li-ion batteries with
      improved energy density because of its high theoretical specific capacity and
      favorable operation voltage range. However, the large volume expansion of Si
      during electrochemical reaction with Li and the associated adverse effects
      strongly limit its prospect for application. Here, we report on the use of three
      dimensional instead of flat current collectors for high-capacity Si anodes in an
      attempt to mitigate the loss of electrical contact of active electrode regions as
      a result of structural disintegration with cycling. The current collectors were
      produced by technical embroidery and consist of interconnected Cu wires of
      diameter <150 um. In comparison to Si/Li cells using a conventional Cu foil
      current collector, the embroidered microwire network-based cells show much
      enhanced capacity and reversibility due to a higher degree of tolerance to
      cycling.

PMID- 29026139
TI  - Partial volume correction for PET quantification and its impact on brain network
      in Alzheimer's disease.
AB  - Amyloid positron emission tomography (PET) imaging is a valuable tool for
      research and diagnosis in Alzheimer's disease (AD). Partial volume effects caused
      by the limited spatial resolution of PET scanners degrades the quantitative
      accuracy of PET image. In this study, we have applied a method to evaluate the
      impact of a joint-entropy based partial volume correction (PVC) technique on
      brain networks learned from a clinical dataset of AV-45 PET image and compare
      network properties of both uncorrected and corrected image-based brain networks.
      We also analyzed the region-wise SUVRs of both uncorrected and corrected images.
      We further performed classification tests on different groups using the same set
      of algorithms with same parameter settings. PVC has sometimes been avoided due to
      increased noise sensitivity in image registration and segmentation, however, our
      results indicate that appropriate PVC may enhance the brain network structure
      analysis for AD progression and improve classification performance.

PMID- 29026141
TI  - Combined skin and muscle vaccination differentially impact the quality of
      effector T cell functions: the CUTHIVAC-001 randomized trial.
AB  - Targeting of different tissues via transcutaneous (TC), intradermal (ID) and
      intramuscular (IM) injection has the potential to tailor the immune response to
      DNA vaccination. In this Phase I randomised controlled clinical trial in HIV-1
      negative volunteers we investigate whether the site and mode of DNA vaccination
      influences the quality of the cellular immune responses. We adopted a strategy of
      concurrent immunization combining IM injection with either ID or TC
      administration. As a third arm we assessed the response to IM injection
      administered with electroporation (EP). The DNA plasmid encoded a MultiHIV B
      clade fusion protein designed to induce cellular immunity. The vaccine and
      regimens were well tolerated. We observed differential shaping of vaccine induced
      virus-specific CD4 + and CD8 + cell-mediated immune responses. DNA given by IM +
      EP promoted strong IFN-gamma responses and potent viral inhibition. ID + IM
      without EP resulted in a similar pattern of response but of lower magnitude. By
      contrast TC + IM (without EP) shifted responses towards a more Th-17 dominated
      phenotype, associated with mucosal and epidermal protection. Whilst preliminary,
      these results offer new perspectives for differential shaping of desired cellular
      immunity required to fight the wide range of complex and diverse infectious
      diseases and cancers.

PMID- 29026142
TI  - Stochastic resonance at criticality in a network model of the human cortex.
AB  - Stochastic resonance is a phenomenon in which noise enhances the response of a
      system to an input signal. The brain is an example of a system that has to detect
      and transmit signals in a noisy environment, suggesting that it is a good
      candidate to take advantage of stochastic resonance. In this work, we aim to
      identify the optimal levels of noise that promote signal transmission through a
      simple network model of the human brain. Specifically, using a dynamic model
      implemented on an anatomical brain network (connectome), we investigate the
      similarity between an input signal and a signal that has traveled across the
      network while the system is subject to different noise levels. We find that non
      zero levels of noise enhance the similarity between the input signal and the
      signal that has traveled through the system. The optimal noise level is not
      unique; rather, there is a set of parameter values at which the information is
      transmitted with greater precision, this set corresponds to the parameter values
      that place the system in a critical regime. The multiplicity of critical points
      in our model allows it to adapt to different noise situations and remain at
      criticality.

PMID- 29026143
TI  - Translesion synthesis DNA polymerase eta exhibits a specific RNA extension
      activity and a transcription-associated function.
AB  - Polymerase eta (Poleta) is a low fidelity translesion synthesis DNA polymerase
      that rescues damage-stalled replication by inserting deoxy-ribonucleotides
      opposite DNA damage sites resulting in error-free or mutagenic damage bypass. In
      this study we identify a new specific RNA extension activity of Poleta of
      Saccharomyces cerevisiae. We show that Poleta is able to extend RNA primers in
      the presence of ribonucleotides (rNTPs), and that these reactions are an order of
      magnitude more efficient than the misinsertion of rNTPs into DNA. Moreover,
      during RNA extension Poleta performs error-free bypass of the 8-oxoguanine and
      thymine dimer DNA lesions, though with a 103 and 102-fold lower efficiency,
      respectively, than it synthesizes opposite undamaged nucleotides. Furthermore, in
      vivo experiments demonstrate that the transcription of several genes is affected
      by the lack of Poleta, and that Poleta is enriched over actively transcribed
      regions. Moreover, inactivation of its polymerase activity causes similar
      transcription inhibition as the absence of Poleta. In summary, these results
      suggest that the new RNA synthetic activity of Poleta can have in vivo relevance.

PMID- 29026144
TI  - Increased NK cell immunity in a transgenic mouse model of NKp46 overexpression.
AB  - Natural Killer (NK) cells employ activating receptors like the Natural
      Cytotoxicity Receptors (NCRs: NKp30, NKp44 and NKp46), of which only NKp46 has a
      mouse orthologue (Ncr1), to eliminate abnormal cells. NKp46/Ncr1 is considered a
      selective marker for NK cells, although it is also found on a subset of ILCs,
      where it appears to be without function. The influenza virus hemagglutinin (HA)
      was the first ligand identified for Ncr1/NKp46 followed by other viral, bacterial
      and even fungal ligands. NKp46/Ncr1 also recognizes unknown self and tumor
      ligands. Here we describe the generation of a transgenic mouse where the Ncr1
      gene is expressed in the Rosa locus, preceded by a floxed stop sequence allowing
      Ncr1/NKp46 expression in various tissues upon crossing with Cre transgenic mouse
      lines. Surprisingly, while several crossings were attempted, Ncr1 overexpression
      was successful only where cre recombinase expression was dependent on the Ncr1
      promoter. Ncr1 overexpression in NK cells increased NK cell immunity in two
      hallmark Ncr1 related pathologies, influenza virus infection and B16 melanoma.
      These data suggest that increasing NK cell cytotoxicity by enforced NKp46/Ncr1
      expression serves as a potential therapeutic opportunity for the treatment of
      various pathologies, and in immunotherapy.

PMID- 29026145
TI  - Cibinetide dampens innate immune cell functions thus ameliorating the course of
      experimental colitis.
AB  - Two distinct forms of the erythropoietin receptor (EPOR) mediate the cellular
      responses to erythropoietin (EPO) in different tissues. EPOR homodimers signal to
      promote the maturation of erythroid progenitor cells. In other cell types,
      including immune cells, EPOR and the beta-common receptor (CD131) form heteromers
      (the innate repair receptor; IRR), and exert tissue protective effects. We used
      dextran sulphate sodium (DSS) to induce colitis in C57BL/6 N mice. Once colitis
      was established, mice were treated with solvent, EPO or the selective IRR agonist
      cibinetide. We found that both cibinetide and EPO ameliorated the clinical course
      of experimental colitis in mice, resulting in improved weight gain and survival.
      Correspondingly, DSS-exposed mice treated with cibinetide or EPO displayed
      preserved tissue integrity due to reduced infiltration of myeloid cells and
      diminished production of pro-inflammatory disease mediators including cytokines,
      chemokines and nitric oxide synthase-2. Experiments using LPS-activated primary
      macrophages revealed that the anti-inflammatory effects of cibinetide were
      dependent on CD131 and JAK2 functionality and were mediated via inhibition of NF
      kappaB subunit p65 activity. Cibinetide activation of the IRR exerts potent anti
      inflammatory effects, especially within the myeloid population, reduces disease
      activity and mortality in mice. Cibinetide thus holds promise as novel disease
      modifying therapeutic of inflammatory bowel disease.

PMID- 29026146
TI  - Multiple Approaches Detect the Presence of Fungi in Human Breastmilk Samples from
      Healthy Mothers.
AB  - Human breastmilk contains a variety of bacteria that are transmitted to the
      infant and have been suggested to contribute to gut microbiota development and
      immune maturation. However, the characterization of fungal organisms in milk from
      healthy mothers is currently unknown although their presence has been reported in
      the infant gut and also in milk from other mammals. Breastmilk samples from
      healthy lactating mothers (n = 65) within 1 month after birth were analyzed.
      Fungal presence was assessed by different techniques, including microscopy,
      growth and identification of cultured isolates, fungal load estimation by qPCR,
      and fungal composition using 28S rRNA gene high-throughput sequencing. In
      addition, milk macronutrients and human somatic cells were quantified by
      spectrophotometry and cytometry. qPCR data showed that 89% of samples had
      detectable levels of fungal DNA, at an estimated median load of 3,5 * 105
      cells/ml, potentially including both viable and non-viable fungi. Using different
      culture media, 33 strains were isolated and identified, confirming the presence
      of viable fungal species. Pyrosequencing results showed that the most common
      genera were Malassezia (44%), followed by Candida (19%) and Saccharomyces (12%).
      Yeast cells were observed by fluorescence microscopy. Future work should study
      the origin of these fungi and their potential contribution to infant health.

PMID- 29026147
TI  - Vascular Endothelial Growth Factor in Cartilage Development and Osteoarthritis.
AB  - Genome wide studies indicate that vascular endothelial growth factor A (VEGF) is
      associated with osteoarthritis (OA), and increased VEGF expression correlates
      with increased disease severity. VEGF is also a chondrocyte survival factor
      during development and essential for bone formation, skeletal growth and
      postnatal homeostasis. This raises questions of how the important embryonic and
      postnatal functions of VEGF can be reconciled with an apparently destructive role
      in OA. Addressing these questions, we find that VEGF acts as a survival factor in
      growth plate chondrocytes during development but only up until a few weeks after
      birth in mice. It is also required for postnatal differentiation of articular
      chondrocytes and the timely ossification of bones in joint regions. In surgically
      induced knee OA in mice, a model of post-traumatic OA in humans, increased
      expression of VEGF is associated with catabolic processes in chondrocytes and
      synovial cells. Conditional knock-down of Vegf attenuates induced OA. Intra
      articular anti-VEGF antibodies suppress OA progression, reduce levels of
      phosphorylated VEGFR2 in articular chondrocytes and synovial cells and reduce
      levels of phosphorylated VEGFR1 in dorsal root ganglia. Finally, oral
      administration of the VEGFR2 kinase inhibitor Vandetanib attenuates OA
      progression.

PMID- 29026149
TI  - The folding, stability and function of lactose permease differ in their
      dependence on bilayer lipid composition.
AB  - Lipids play key roles in Biology. Mechanical properties of the lipid bilayer
      influence their neighbouring membrane proteins, however it is unknown whether
      different membrane protein properties have the same dependence on membrane
      mechanics, or whether mechanics are tuned to specific protein processes of the
      protein. We study the influence of lipid lateral pressure and electrostatic
      effects on the in vitro reconstitution, folding, stability and function of a
      representative of the ubiquitous major facilitator transporter superfamily,
      lactose permease. Increasing the outward chain lateral pressure in the bilayer,
      through addition of lamellar phosphatidylethanolamine lipids, lowers lactose
      permease folding and reconstitution yields but stabilises the folded state. The
      presence of phosphatidylethanolamine is however required for correct folding and
      function. An increase in headgroup negative charge through the addition of
      phosphatidylglycerol lipids favours protein reconstitution but is detrimental to
      topology and function. Overall the in vitro folding, reconstitution, topology,
      stability and function of lactose permease are found to have different
      dependences on bilayer composition. A regime of lipid composition is found where
      all properties are favoured, even if suboptimal. This lays ground rules for
      rational control of membrane proteins in nanotechnology and synthetic biology by
      manipulating global bilayer properties to tune membrane protein behaviour.

PMID- 29026148
TI  - Exclusive and Combined Use of Statins and Aspirin and the Risk of Pancreatic
      Cancer: a Case-Control Study.
AB  - Data on the association between aspirin and statin use and Pancreatic Ductal
      AdenoCarcinoma (PDAC) risk are conflicting. These drugs are often co-prescribed,
      but no studies evaluated the potential combined or confounding effect of the two
      at the same time. We aimed to investigate the association between aspirin and
      statin exclusive and combined use and PDAC occurrence. Data on environmental
      factors, family and medical history were screened in a case-control study. PDAC
      cases were matched to controls for age and gender. Power calculation performed
      ahead. Odds ratios (OR) and 95% confidence intervals(CI) were obtained from
      multivariable logistic regression analysis. In 408 PDAC patients and 816 matched
      controls, overall statin (OR 0.61; 95%CI,0.43-0.88), but not aspirin use was
      associated to reduced PDAC risk. Compared to non-users, exclusive statin (OR
      0.51; 95%CI,0.32-0.80) and exclusive aspirin users (OR 0.64; 95%CI,0.40-1.01) had
      reduced PDAC risk. Concomitant statin and aspirin use did not further reduce the
      risk compared with statin use alone and no interaction was evident. Statin
      protective association was dose-dependent, and consistent in most subgroups,
      being stronger in smokers, elderly, obese and non-diabetic patients. The present
      study suggests that statin use is associated to reduced PDAC risk, supporting a
      chemopreventive action of statins on PDAC.

PMID- 29026150
TI  - Essential role of the Na+-Ca2+ exchanger (NCX) in glutamate-enhanced cell
      survival in cardiac cells exposed to hypoxia/reoxygenation.
AB  - Myocardial ischemia culminates in ATP production impairment, ionic derangement
      and cell death. The provision of metabolic substrates during reperfusion
      significantly increases heart tolerance to ischemia by improving mitochondrial
      performance. Under normoxia, glutamate contributes to myocardial energy balance
      as substrate for anaplerotic reactions, and we demonstrated that the Na+/Ca2+
      exchanger1 (NCX1) provides functional support for both glutamate uptake and use
      for ATP synthesis. Here we investigated the role of NCX1 in the potential of
      glutamate to improve energy metabolism and survival of cardiac cells subjected to
      hypoxia/reoxygenation (H/R). Specifically, in H9c2-NCX1 myoblasts, ATP levels,
      mitochondrial activities and cell survival were significantly compromised after
      H/R challenge. Glutamate supplementation at the onset of the reoxygenation phase
      significantly promoted viability, improved mitochondrial functions and normalized
      the H/R-induced increase of NCX1 reverse-mode activity. The benefits of glutamate
      were strikingly lost in H9c2-WT (lacking NCX1 expression), or in H9c2-NCX1 and
      rat cardiomyocytes treated with either NCX or Excitatory Amino Acid Transporters
      (EAATs) blockers, suggesting that a functional interplay between these
      transporters is critically required for glutamate-induced protection.
      Collectively, these results revealed for the first time the key role of NCX1 for
      the beneficial effects of glutamate against H/R-induced cell injury.

PMID- 29026151
TI  - Synthesis and Absorption Properties of Hollow-spherical Dy2Cu2O5 via a
      Coordination Compound Method with [DyCu(3,4-pdc)2(OAc)(H2O)2]*10.5H2O Precursor.
AB  - Dy2Cu2O5 nanoparticles with perovskite structures were synthesized via a simple
      solution method (SSM) and a coordination compound method (CCM) using [DyCu(3,4
      pdc)2(OAc)(H2O)2]*10.5H2O (pdc = 3,4-pyridinedicarboxylic acid) as precursor. The
      as-prepared samples were structurally characterized by X-ray diffraction (XRD),
      scanning electron microscopy (SEM), high-resolution transmission electron
      microscopy (HRTEM), x-ray photoelectron spectroscopy (XPS) and standard Brunauer
      Emmett-Teller (BET) methods. Compared to the aggregated hexahedral particles
      prepared by SSM, the Dy2Cu2O5 of CCM showed hollow spherical morphology composed
      of nanoparticles with average diameters of 100-150 nm and a larger special
      surface area up to 36.5 m2/g. The maximum adsorption capacity (Q m ) of CCM for
      malachite green (MG) determined by the adsorption isotherms with different
      adsorbent dosages of 0.03-0.07 g, reached 5.54 g/g at room temperature. The
      thermodynamic parameters of adsorption process were estimated by the fittings of
      the isotherms at 298, 318, and 338 K, and the kinetic parameters were obtained
      from the time-dependent adsorption isotherms. The results revealed that the
      adsorption process followed a pseudo-second-order reaction. Finally, the
      adsorption mechanism was studied using a competitive ion (CI) experiments, and
      the highly efficient selective adsorption was achieved due to strong O-Cu and O
      Dy coordination bonds between Dy2Cu2O5 and MG.

PMID- 29026152
TI  - Genetic and Epigenetic Profiling Reveals EZH2-mediated Down Regulation of OCT-4
      Involves NR2F2 during Cardiac Differentiation of Human Embryonic Stem Cells.
AB  - Human embryonic (hES) stem cells are widely used as an in vitro model to
      understand global genetic and epigenetic changes that occur during early
      embryonic development. In-house derived hES cells (KIND1) were subjected to
      directed differentiation into cardiovascular progenitors (D12) and beating
      cardiomyocytes (D20). Transcriptome profiling of undifferentiated (D0) and
      differentiated (D12 and 20) cells was undertaken by microarray analysis. ChIP and
      sequential ChIP were employed to study role of transcription factor NR2F2 during
      hES cells differentiation. Microarray profiling showed that an alteration of
      about 1400 and 1900 transcripts occurred on D12 and D20 respectively compared to
      D0 whereas only 19 genes were altered between D12 and D20. This was found
      associated with corresponding expression pattern of chromatin remodelers, histone
      modifiers, miRNAs and lncRNAs marking the formation of progenitors and
      cardiomyocytes on D12 and D20 respectively. ChIP sequencing and sequential ChIP
      revealed the binding of NR2F2 with polycomb group member EZH2 and pluripotent
      factor OCT4 indicating its crucial involvement in cardiac differentiation. The
      study provides a detailed insight into genetic and epigenetic changes associated
      with hES cells differentiation into cardiac cells and a role for NR2F2 is
      deciphered for the first time to down-regulate OCT-4 via EZH2 during cardiac
      differentiation.

PMID- 29026153
TI  - Climate change-induced increases in precipitation are reducing the potential for
      solar ultraviolet radiation to inactivate pathogens in surface waters.
AB  - Climate change is accelerating the release of dissolved organic matter (DOM) to
      inland and coastal waters through increases in precipitation, thawing of
      permafrost, and changes in vegetation. Our modeling approach suggests that the
      selective absorption of ultraviolet radiation (UV) by DOM decreases the valuable
      ecosystem service wherein sunlight inactivates waterborne pathogens. Here we
      highlight the sensitivity of waterborne pathogens of humans and wildlife to solar
      UV, and use the DNA action spectrum to model how differences in water
      transparency and incident sunlight alter the ability of UV to inactivate
      waterborne pathogens. A case study demonstrates how heavy precipitation events
      can reduce the solar inactivation potential in Lake Michigan, which provides
      drinking water to over 10 million people. These data suggest that widespread
      increases in DOM and consequent browning of surface waters reduce the potential
      for solar UV inactivation of pathogens, and increase exposure to infectious
      diseases in humans and wildlife.

PMID- 29026154
TI  - Associations of interactions between NLRP3 SNPs and HLA mismatch with acute and
      extensive chronic graft-versus-host diseases.
AB  - HLA matching is a well-known genetic requirement for successful bone marrow
      transplantation (BMT). However, the importance of non-HLA single-nucleotide
      polymorphisms (SNPs) remains poorly understood. The NLR family pyrin domain
      containing 3 (NLRP3) inflammasome, a key regulator of innate immunity, is
      associated with multiple diseases. We retrospectively genotyped SNPs of NLRP1-3
      and caspase recruitment domain family member 8 (CARD8), which are implicated in
      the interleukin 1beta (IL-1beta) signaling, in 999 unrelated BMT donor-recipient
      pairs. We identified an association of the interaction between the recipient
      NLRP3 SNP CC genotype and total HLA mismatches with grade 2-4 acute graft-versus
      host disease (AGVHD), and an association of the interaction between the donor
      NLRP3 SNP T allele and HLA-C mismatch with extensive chronic GVHD (ECGVHD), in
      both adjusted and unadjusted regressions (P < 0.005). Importantly, the ECGVHD
      risk associated with HLA-C mismatch was not elevated when the donor NLRP3
      genotype was CC. We also identified an association of the interaction between
      recipient NLRP3 SNP and donor cytomegalovirus seropositivity with overall
      survival in adjusted regressions (P < 0.005). These results suggest the
      importance of certain SNP-covariate interactions in unrelated BMT. The three
      identified interactions may be useful for donor selection or outcome prediction.

PMID- 29026155
TI  - Trk-fused gene (TFG) regulates pancreatic beta cell mass and insulin secretory
      activity.
AB  - The Trk-fused gene (TFG) is reportedly involved in the process of COPII-mediated
      vesicle transport and missense mutations in TFG cause several neurodegenerative
      diseases including hereditary motor and sensory neuropathy with proximal dominant
      involvement (HMSN-P). The high coincidence ratio between HMSN-P and diabetes
      mellitus suggests TFG to have an important role(s) in glucose homeostasis. To
      examine this possibility, beta-cell specific TFG knockout mice (betaTFG KO) were
      generated. Interestingly, betaTFG KO displayed marked glucose intolerance with
      reduced insulin secretion. Immunohistochemical analysis revealed smaller beta
      cell masses in betaTFG KO than in controls, likely attributable to diminished
      beta-cell proliferation. Consistently, beta-cell expansion in response to a high
      fat, high-sucrose (HFHS) diet was significantly impaired in betaTFG KO.
      Furthermore, glucose-induced insulin secretion was also markedly impaired in
      islets isolated from betaTFG KO. Electron microscopic observation revealed
      endoplasmic reticulum (ER) dilatation, suggestive of ER stress, and smaller
      insulin crystal diameters in beta-cells of betaTFG KO. Microarray gene expression
      analysis indicated downregulation of NF-E2 related factor 2 (Nrf2) and its
      downstream genes in TFG depleted islets. Collectively, TFG in pancreatic beta
      cells plays a vital role in maintaining both the mass and function of beta-cells,
      and its dysfunction increases the tendency to develop glucose intolerance.

PMID- 29026156
TI  - Metabolic Responses of Eisenia Fetida to Individual Pb and Cd Contamination in
      Two Types of Soils.
AB  - To characterize the potential toxicity of low Pb- and Cd-contaminated arable
      soils, earthworms were exposed to Pb contaminated ferrosol, cambosol or Cd
      contaminated ferrosol for two weeks. Polar metabolites of earthworms were
      detected by nuclear magnetic resonance. Data were then analyzed with principal
      component analysis followed by orthogonal signal correction-partial least squares
      discriminant analysis and univariate analysis to determine possible mechanisms
      for the changes in metabolites. The survival rates, metal concentrations and
      bioaccumulation factor (BAF) of the earthworms were also measured and calculated
      as auxiliary data. The results showed that the metabolite profiles were highly
      similar in Pb-contaminated ferrosol and cambosol (R2 = 0.76, p < 0.0001), which
      can be attributed to similar response mechanisms. However, there was a more
      intense response in ferrosol likely due to higher Pb concentrations in
      earthworms. Metabolic pathways and BAFs exhibited apparent distinctions between
      Pb- and Cd-contaminated ferrosol, likely because they bind to different bio
      ligands. The affected metabolic pathways were involved in alanine-aspartate
      glutamate, purine, glutathione, valine-leucine-isoleucine biosynthesis and
      degradation and nicotinate and nicotinamide metabolism. Regarding the
      bioavailability in earthworms, Pb availability was higher for ferrosol than for
      cambosol. We confirmed that the potential toxicity of low Pb/Cd-contaminated
      soils can be characterized using earthworm metabolomics.

PMID- 29026157
TI  - Bortezomib promotes KHSV and EBV lytic cycle by activating JNK and autophagy.
AB  - KSHV and EBV are gammaherpesviruses strictly linked to human cancers. Even if the
      majority of cancer cells harbor a latent infection, the few cells that undergo
      viral replication may contribute to the pathogenesis and maintenance of the virus
      associated malignancies. Cytotoxic drugs used for the therapies of cancers
      harboring virus-infection often have, as side effect, the activation of viral
      lytic cycle. Therefore it is important to investigate whether they affect viral
      reactivation and understand the underlying mechanisms involved. In this study, we
      found that proteasome inhibitor bortezomib, a cytotoxic drug that efficiently
      target gammaherpesvirus-associated B cell lymphomas, triggered KSHV or EBV viral
      lytic cycle by activating JNK, in the course of ER stress, and inducing
      autophagy. These results suggest that the manipulation of these pathways could
      limit viral spread and improve the outcome of bortezomib treatment in patients
      affected by gammaherpesvirus-associated lymphomas.

PMID- 29026158
TI  - Ginsenoside Rb1 prevents homocysteine-induced EPC dysfunction via VEGF/p38MAPK
      and SDF-1/CXCR4 activation.
AB  - Hyperhomocystinemia (HHcy) is known as an independent risk factor for
      cardiovascular disease. Our previous study showed that ginsenoside Rb1, the major
      active constituent of ginseng, prevents homocysteine (Hcy)-induced endothelial
      damage. However, the role of ginsenoside Rb1 in Hcy-induced dysfunction in
      endothelial progenitor cells (EPCs) remains unknown. In the study, we found that
      ginsenoside Rb1 reversed the Hcy-induced impairment of adhesive and migratory
      ability in EPCs which were significantly abolished by CXCR4 antagonist AMD3100
      and VEGFR2 inhibitor SU5416. Ginsenoside Rb1 significantly reversed Hcy-induced
      SDF-1 reduction in the supernatant and in the serum. Ginsenoside Rb1 reversed
      downregulation of SDF-1 and VEGFR2 protein expression, inhibition of p38MAPK
      phosphorylation induced by Hcy. Re-endothelialization in balloon-injured carotid
      arteries significantly increased with EPCs transplant, and was even better with
      Rb1 treatment. This effect was significantly abolished by AMD3100. AMD3100 also
      decreased the number of CM-DiI labeled EPCs in injured arteries. Here we show for
      the first time that Rb1 prevents Hcy-induced EPC dysfunction via VEGF/p38MAPK and
      SDF-1/CXCR4 activation. These findings demonstrate a novel mechanism of the
      action of Rb1 that may have value in prevention of HHcy associated cardiovascular
      disease.

PMID- 29026159
TI  - Spectrum of spontaneous photon emission as a promising biophysical indicator for
      breast cancer research.
AB  - In this study, we investigated the spectral characteristics of Spontaneous Photon
      Emission (SPE) from the body surface of a human breast cancer-bearing nude mice
      model during the overall growth process of breast cancers. By comparing and
      analyzing the data, we found that there was a striking difference between tumor
      mice and healthy controls in the spectral distribution of SPE from the body
      surface of lesion site, even when the morphological changes at the lesion site
      were not obvious. The spectral distribution of SPE from the healthy site of the
      tumor mice also differed from that of the healthy controls as the breast cancer
      developed to a certain stage. In addition, the difference in spectrum was related
      with different growth states of tumors. Interestingly, there was a positive
      correlation between the spectral ratio (610-630/395-455 nm) and the logarithm of
      the tumor volume for both the lesion site (R2 = 0.947; p < 0.001) and the normal
      site (R2 = 0.892; p < 0.001) of the tumor mice. The results suggested that the
      spectrum of SPE was sensitive to changes in the tumor status.

PMID- 29026160
TI  - Small-angle neutron scattering modeling of spin disorder in nanoparticles.
AB  - Magnetic small-angle neutron scattering (SANS) is a powerful technique for
      investigating magnetic nanoparticle assemblies in nonmagnetic matrices. For such
      microstructures, the standard theory of magnetic SANS assumes uniformly
      magnetized nanoparticles (macrospin model). However, there exist many
      experimental and theoretical studies which suggest that this assumption is
      violated: deviations from ellipsoidal particle shape, crystalline defects, or the
      interplay between various magnetic interactions (exchange, magnetic anisotropy,
      magnetostatics, external field) may lead to nonuniform spin structures.
      Therefore, a theoretical framework of magnetic SANS of nanoparticles needs to be
      developed. Here, we report numerical micromagnetic simulations of the static spin
      structure and related unpolarized magnetic SANS of a single cobalt nanorod. While
      in the saturated state the magnetic SANS cross section is (as expected)
      determined by the particle form factor, significant deviations appear for
      nonsaturated states; specifically, at remanence, domain-wall and vortex states
      emerge which result in a magnetic SANS signal that is composed of all three
      magnetization Fourier components, giving rise to a complex angular anisotropy on
      a two-dimensional detector. The strength of the micromagnetic simulation
      methodology is the possibility to decompose the cross section into the individual
      Fourier components, which allows one to draw important conclusions regarding the
      fundamentals of magnetic SANS.

PMID- 29026161
TI  - In vivo noninvasive microscopy of human leucocytes.
AB  - Leucocytes play a key role in our immune system, protecting the body against
      infections using a wide range of biological mechanisms. Effective imaging and
      identification of leucocytes within the blood stream in patients is challenging,
      however, because of their low volume fraction in the blood, the high tissue
      scattering and the rapid blood flow. Spectrally encoded flow cytometry (SEFC) has
      recently been demonstrated effective for label-free high-resolution in vivo
      imaging of blood cells using an optical probe that does not require mechanical
      scanning. Here, we use SEFC to noninvasively image leucocytes at different
      imaging depths within small vessels in human volunteers, and identify visual
      differences in cell brightness and nuclei shapes, that would help distinguish
      between the two most abundant leucocyte types. The observed differences match the
      in vitro characteristics of isolated granulocytes and mononuclear cells. The
      results prove the potential of the system for conducting differential leucocyte
      count and as an effective research tool for studying the function and
      distribution of leucocytes in humans.

PMID- 29026162
TI  - Improving membrane protein expression and function using genomic edits.
AB  - Expression of membrane proteins often leads to growth inhibition and perturbs
      central metabolism and this burden varies with the protein being overexpressed.
      There are also known strain backgrounds that allow greater expression of membrane
      proteins but that differ in efficacy across proteins. We hypothesized that for
      any membrane protein, it may be possible to identify a modified strain background
      where its expression can be accommodated with less burden. To directly test this
      hypothesis, we used a bar-coded transposon insertion library in tandem with cell
      sorting to assess genome-wide impact of gene deletions on membrane protein
      expression. The expression of five membrane proteins (CyoB, CydB, MdlB, YidC, and
      LepI) and one soluble protein (GST), each fused to GFP, was examined. We
      identified Escherichia coli mutants that demonstrated increased membrane protein
      expression relative to that in wild type. For two of the proteins (CyoB and
      CydB), we conducted functional assays to confirm that the increase in protein
      expression also led to phenotypic improvement in function. This study represents
      a systematic approach to broadly identify genetic loci that can be used to
      improve membrane protein expression, and our method can be used to improve
      expression of any protein that poses a cellular burden.

PMID- 29026164
TI  - Production and evaluation of parathyroid hormone receptor1 ligands with intrinsic
      or assembled peroxidase domains.
AB  - Parathyroid hormone (PTH) can be C-terminally extended without significant
      affinity loss for the PTH1 receptor (PTHR1). We developed fusion protein ligands
      with enzymatic activity to probe PTHR1s at the cell surface. Two fusion proteins
      were generated by linking PTH to the N-terminus of either horseradish peroxidase
      (PTH-HRP) or the genetically modified soybean peroxidase APEX2 (PTH-APEX2).
      Alternatively, myc-tagged PTH (PTH-myc) was combined with antibodies, some of
      which HRP-conjugated, in the extracellular fluid. The three PTH-fusion proteins
      were produced as conditioned mediums (CM) by transfected producer HEK 293a cells.
      Binding of receptor-bound enzymatic ligands was revealed using widely available
      substrate/co-substrate systems. The stimulation of recipient HEK 293a expressing
      PTHR1s with the PTH-myc/antibodies combination or with PTH-APEX2 supported the
      histochemical or luminescent detection of recombinant PTHR1s (TrueBlueTM or
      luminol-based reagent). The PTH-HRP construction was the most sensitive and
      supported all tested peroxidase co-substrates (TrueBlueTM, tetramethylbenzidine
      (TMB), luminol, biotin-phenol with streptavidin-Qdots); the 3 latter schemes
      identified endogenous PTHR1 in the osteoblastic HOS cell line. The specificity of
      the fusion protein binding to PTHR1 was determined by its competition with an
      excess of PTH1-34. Bifunctional ligands possessing enzymatic activity detect
      intact receptors with various possible applications, including the screening of
      drugs that compete for receptor binding.

PMID- 29026165
TI  - Appropriate surgical modalities for stages T2a and T2b in the eighth TNM
      classification of lung cancer.
AB  - Patients with tumors of 3 to 5 cm were divided into stages T2a (3 to 4 cm) and
      T2b (4 to 5 cm) based on the 8th tumor-node-metastasis staging system for lung
      cancer. The objective of our study was to explore appropriate surgical modalities
      for the new stages, T2a and T2b. We selected 6,996 node-negative non-small-cell
      lung cancer patients with tumor sizes of 3 to 5 cm, diagnosed between 2009 and
      2013, from the Surveillance, Epidemiology, and End Results (SEER) program. The
      Pearson [Formula: see text]. statistic test and Kaplan-Meier curve were used to
      analyze patient data. The prognosis of patients with stage T2a was significantly
      better than that of patients with stage T2b, both in overall survival (p = 0.018)
      and lung cancer specific survival (p = 0.001). For patients with stage T2a,
      lobectomy had a significantly better outcome. For patients with stage T2b,
      surgical modalities including pneumonectomy, segmental resection and lobectomy,
      had similar outcomes in terms of survival. Consequently, lobectomy was the most
      appropriate surgical treatment modality for new stage T2a patients, whereas, for
      new T2b patients, treatment outcome did not vary significantly with the choice of
      surgical modality.

PMID- 29026163
TI  - Revealing the Saline Adaptation Strategies of the Halophilic Bacterium Halomonas
      beimenensis through High-throughput Omics and Transposon Mutagenesis Approaches.
AB  - Studies on the halotolerance of bacteria are attractive to the fermentation
      industry. However, a lack of sufficient genomic information has precluded an
      investigation of the halotolerance of Halomonas beimenensis. Here, we describe
      the molecular mechanisms of saline adaptation in H. beimenensis based on high
      throughput omics and Tn5 transposon mutagenesis. The H. beimenensis genome is
      4.05 Mbp and contains 3,807 genes, which were sequenced using short and long
      reads obtained via deep sequencing. Sixteen Tn5 mutants with a loss of
      halotolerance were identified. Orthologs of the mutated genes, such as nqrA,
      trkA, atpC, nadA, and gdhB, have significant biological functions in sodium
      efflux, potassium uptake, hydrogen ion transport for energy conversion, and
      compatible solute synthesis, which are known to control halotolerance. Other
      genes, such as spoT, prkA, mtnN, rsbV, lon, smpB, rfbC, rfbP, tatB, acrR1, and
      lacA, function in cellular signaling, quorum sensing, transcription/translation,
      and cell motility also shown critical functions for promoting a halotolerance. In
      addition, KCl application increased halotolerance and potassium-dependent cell
      motility in a high-salinity environment. Our results demonstrated that a
      combination of omics and mutagenesis could be used to facilitate the mechanistic
      exploitation of saline adaptation in H. beimenensis, which can be applied for
      biotechnological purposes.

PMID- 29026166
TI  - Virus and host-specific differences in oral human herpesvirus shedding kinetics
      among Ugandan women and children.
AB  - Human herpesviruses (HHV) establish lifelong latent infection and are transmitted
      primarily via shedding at mucosal surfaces. Each HHV causes a unique spectrum of
      disease depending on the infected individual's age and immunity. We collected
      weekly oral swabs from young children and mothers in 32 Ugandan households for a
      median of one year. We characterized kinetics of oral shedding during primary and
      chronic infection for each virus. Cytomegalovirus (CMV), Epstein-Barr virus
      (EBV), and HHV-6 were shed at high rates following primary infection. The rate of
      oral herpes simplex virus (HSV) shedding was lower overall, and children and
      mothers with chronic HSV infection had lower shedding rates than children with
      primary infection. CMV shedding rate and viral load were higher in children with
      primary infection compared to children with chronic infection, and even lower in
      mothers with chronic infection. HHV-6 shedding rate and viral load were similar
      between children with primary or chronic infection, but lower in mothers. EBV
      shedding rate and quantity decreased less dramatically in mothers versus
      children, with HIV-positive mothers shedding at a higher rate than HIV-negative
      mothers. Each HHV has a distinct pattern of oral shedding which depends partially
      on the age and immune status of the host.

PMID- 29026167
TI  - The proteasome inhibitor bortezomib attenuates renal fibrosis in mice via the
      suppression of TGF-beta1.
AB  - Kidney fibrosis and fibrogenesis significantly exacerbate chronic kidney disease
      (CKD) progression and are essential therapeutic targets. Bortezomib (BZM) is a
      proteasome inhibitor used for the treatment of multiple myeloma (MM). Several
      studies have demonstrated that BZM attenuates renal impairment in patients with
      MM, although this effect is generally considered to be the result of MM
      remission. Recently, several studies on BZM reported anti-fibrotic effects on
      liver and skin in experimental animal models. However, its effect on renal
      fibrosis has yet to be examined. Here, we investigated the anti-fibrotic effects
      of BZM in an experimental mouse model of fibrosis that uses aristolochic acid I
      (AA). Ten weeks of AA administration with BZM treatment twice a week
      significantly attenuated AA-induced renal dysfunction and albuminuria, reduced
      the expression of renal fibrosis-related proteins and kidney injury markers, such
      as alphaSMA, Kim1, and Ngal, and prevented renal fibrosis at the level of
      histopathology. Furthermore, pathological activation of TGFbeta1-Smad3 signaling
      and apoptosis, essential pathophysiological causes of AA-induced nephropathy
      (AAN), were ameliorated by BZM, suggesting this mechanism may be involved in
      improving fibrosis in AAN. In conclusion, BZM directly inhibits renal fibrosis in
      CKD via suppression of TGFbeta1-Smad3 signaling and is promising in terms of drug
      repositioning.

PMID- 29026169
TI  - Potential impacts of climate change on habitat suitability for the Queensland
      fruit fly.
AB  - Anthropogenic climate change is a major factor driving shifts in the
      distributions of pests and invasive species. The Queensland fruit fly, Bactrocera
      tryoni Froggatt (Qfly), is the most economically damaging insect pest of
      Australia's horticultural industry, and its management is a key priority for
      plant protection and biosecurity. Identifying the extent to which climate change
      may alter the distribution of suitable habitat for Qfly is important for the
      development and continuation of effective monitoring programs, phytosanitary
      measures, and management strategies. We used Maxent, a species distribution
      model, to map suitable habitat for Qfly under current climate, and six climate
      scenarios for 2030, 2050 and 2070. Our results highlight that south-western
      Australia, northern regions of the Northern Territory, eastern Queensland, and
      much of south-eastern Australia are currently suitable for Qfly. This includes
      southern Victoria and eastern Tasmania, which are currently free of breeding
      populations. There is substantial agreement across future climate scenarios that
      most areas currently suitable will remain so until at least 2070. Our projections
      provide an initial estimate of the potential exposure of Australia's
      horticultural industry to Qfly as climate changes, highlighting the need for long
      term vigilance across southern Australia to prevent further range expansion of
      this species.

PMID- 29026168
TI  - Gene losses and partial deletion of small single-copy regions of the chloroplast
      genomes of two hemiparasitic Taxillus species.
AB  - Numerous variations are known to occur in the chloroplast genomes of parasitic
      plants. We determined the complete chloroplast genome sequences of two
      hemiparasitic species, Taxillus chinensis and T. sutchuenensis, using Illumina
      and PacBio sequencing technologies. These species are the first members of the
      family Loranthaceae to be sequenced. The complete chloroplast genomes of T.
      chinensis and T. sutchuenensis comprise circular 121,363 and 122,562 bp-long
      molecules with quadripartite structures, respectively. Compared with the
      chloroplast genomes of Nicotiana tabacum and Osyris alba, all ndh genes as well
      as three ribosomal protein genes, seven tRNA genes, four ycf genes, and the infA
      gene of these two species have been lost. The results of the maximum likelihood
      and neighbor-joining phylogenetic trees strongly support the theory that
      Loranthaceae and Viscaceae are monophyletic clades. This research reveals the
      effect of a parasitic lifestyle on the chloroplast structure and genome content
      of T. chinensis and T. sutchuenensis, and enhances our understanding of the
      discrepancies in terms of assembly results between Illumina and PacBio.

PMID- 29026170
TI  - Randomized clinical trial: Effective gluten degradation by Aspergillus niger
      derived enzyme in a complex meal setting.
AB  - The Aspergillus niger-derived prolyl endoprotease (AN-PEP) has previously been
      shown to degrade gluten in healthy subjects when added to an intragastrically
      infused meal. The current study investigated the efficacy of AN-PEP in a
      physiological meal setting. In this randomized placebo-controlled crossover
      study, 18 gluten-sensitive subjects consumed a porridge containing 0.5 g gluten
      together with two tablets either containing a high or low dose of AN-PEP, or
      placebo. Gastric and duodenal content was sampled over 180 minutes, and areas
      under the curve of gluten concentrations were calculated. The primary outcome,
      i.e. success rate of high dose AN-PEP defined as at least 50% gluten degradation
      compared to placebo in the duodenum, was achieved in 10 of 13 comparisons. In the
      stomach, gluten levels were reduced from 176.9 (median, interquartile range 73.5
      357.8) to 22.0 (10.6-50.8, p = 0.001) in the high dose and to 25.4 MUg * min/ml
      (16.4-43.7, p = 0.001) in the low dose. In the duodenum, gluten levels were
      reduced from 14.1 (8.3-124.7) in the placebo to 6.3 (3.5-19.8, p = 0.019) in the
      high dose and to 7.4 MUg * min/ml in the low dose (3.8-12.0, p = 0.015). Thus
      even in a physiological meal setting, AN-PEP significantly degraded most gluten
      in the stomach before it entered the duodenum.

PMID- 29026171
TI  - Characterization and genomic study of "phiKMV-Like" phage PAXYB1 infecting
      Pseudomonas aeruginosa.
AB  - Bacteriophage PAXYB1 was recently isolated from wastewater samples. This phage
      was chosen based on its lytic properties against clinical isolates of Pseudomonas
      aeruginosa (P. aeruginosa). In the present study, characterized PAXYB1, clarified
      its morphological and lytic properties, and analyzed its complete genome
      sequence. Based on the morphology of PAXYB1, it is a Podoviridae. The linear GC
      rich (62.29%) double-stranded DNA genome of PAXYB1 is 43,337 bp including direct
      terminal repeats (DTRs) of 468 bp. It contains 60 open reading frames (ORFs) that
      are all encoded within the same strand. We also showed that PAXYB1 is a virulent
      phage and a new member of the phiKMV-like phages genus. Twenty-eight out of sixty
      predicted gene products (gps) showed significant homology to proteins of known
      function, which were confirmed by analyzing the structural proteome. Altogether,
      our work identified a novel lytic bacteriophage that lyses P. aeruginosa PAO1 and
      efficiently infects and kills several clinical isolates of P. aeruginosa. This
      phage has potential for development as a biological disinfectant to control P.
      aeruginosa infections.

PMID- 29026172
TI  - Mitochondrial glycerol 3-phosphate facilitates bumblebee pre-flight
      thermogenesis.
AB  - Bumblebees (Bombus terrestris) fly at low ambient temperatures where other
      insects cannot, and to do so they must pre-warm their flight muscles. While some
      have proposed mechanisms, none fully explain how pre-flight thermogenesis occurs.
      Here, we present a novel hypothesis based on the less studied mitochondrial
      glycerol 3-phosphate dehydrogenase pathway (mGPDH). Using calorimetry, and high
      resolution respirometry coupled with fluorimetry, we report substrate oxidation
      by mGPDH in permeabilised flight muscles operates, in vitro, at a high flux, even
      in the absence of ADP. This may be facilitated by an endogenous, mGPDH-mediated
      uncoupling of mitochondria. This uncoupling increases ETS activity, which results
      in increased heat release. Furthermore, passive regulation of this mechanism is
      achieved via dampened temperature sensitivity of mGPDH relative to other
      respiratory pathways, and subsequent consumption of its substrate, glycerol 3
      phosphate (G3P), at low temperatures. Mitochondrial GPDH may therefore facilitate
      pre-flight thermogenesis through poor mitochondrial coupling. We calculate this
      can occur at a sufficient rate to warm flight muscles until shivering commences,
      and until flight muscle function is adequate for bumblebees to fly in the cold.

PMID- 29026174
TI  - The chemical states and atomic structure evolution of ultralow-energy high-dose
      Boron implanted Si(110) via laser annealing.
AB  - Further scale down the dimension of silicon-based integrated circuit is a crucial
      trend in semiconductor fabrication. One of the most critical issues in the nano
      device fabrication is to confirm the atomic structure evolution of the ultrathin
      shallow junction. In this report, UV Raman spectroscopy, X-ray photoelectron
      spectroscopy (XPS), X-ray absorption near edge structure (XANES) and reflective
      second harmonic generation (RSHG) are utilized to monitor the pulse laser induced
      atomic structure evolution of ultralow-energy high-dose Boron implanted Si(110)
      at room and cold substrate temperature. A peak feature around 480 cm-1 resolved
      in UV Raman spectra indicates the formation of Si-B bond after the laser
      irradiation. The red shift of binding energy of Si element (~99 eV) in XPS and
      the evolution of absorption peak (~196.2 eV) in XANES reveal that the changes in
      the chemical states of ultra shallow junction strongly correlate to the
      activation process of Boron implantation, which is confirmed by RSHG measurement.
      The substrate temperature effect in the recrystallization of Boron implanted
      region is also realized by cross-section high-resolution TEM (HRTEM). The
      phenomena of Si-B bond formation and ultra-shallow junction recrystallization can
      be traced and applied to improve the reliability of Si ultra shallow junction in
      the future.

PMID- 29026173
TI  - Three-Dimensional SERS Substrates Formed with Plasmonic Core-Satellite
      Nanostructures.
AB  - We demonstrate three-dimensional surface-enhanced Raman spectroscopy (SERS)
      substrates formed by accumulating plasmonic nanostructures that are synthesized
      using a DNA-assisted assembly method. We densely immobilize Au nanoparticles
      (AuNPs) on polymer beads to form core-satellite nanostructures for detecting
      molecules by SERS. The experimental parameters affecting the AuNP immobilization,
      including salt concentration and the number ratio of the AuNPs to the polymer
      beads, are tested to achieve a high density of the immobilized AuNPs. To create
      electromagnetic hot spots for sensitive SERS sensing, we add a Ag shell to the
      AuNPs to reduce the interparticle distance further, and we carefully adjust the
      thickness of the shell to optimize the SERS effects. In addition, to obtain
      sensitive and reproducible SERS results, instead of using the core-satellite
      nanostructures dispersed in solution directly, we prepare SERS substrates
      consisting of closely packed nanostructures by drying nanostructure-containing
      droplets on hydrophobic surfaces. The densely distributed small and well
      controlled nanogaps on the accumulated nanostructures function as three
      dimensional SERS hot spots. Our results show that the SERS spectra obtained using
      the substrates are much stronger and more reproducible than that obtained using
      the nanostructures dispersed in solution. Sensitive detection of melamine and
      sodium thiocyanate (NaSCN) are achieved using the SERS substrates.

PMID- 29026175
TI  - Efficient reduction of nitric oxide using zirconium phosphide powders synthesized
      by elemental combination method.
AB  - Zirconium phosphide (ZrP) powders were synthesized by elemental combination
      method via the direct reaction of zirconium powders with red phosphorus, and
      characterized by XRD, SEM, XPS, XRF, SAED and TEM measurements. The obtained ZrP
      powders were found to exhibit apparent activity in the ready eliminateion of
      nitric oxide (NO) via facile redox reactions, and the elimination dynamics was
      evaluated within the context of various important experimental parameters, such
      as reaction temperature and gas concentration. At a fixed amount of ZrP powders,
      an increasing amount of NO would be eliminated with increasing reaction
      temperature, and complete conversion of NO to N2 could be reached in the range of
      700 to 800  degrees C. The addition of NH3 also facilitated NO elimination at a
      fixed reaction temperature. Furthermore, of the products of the elimination
      process, zirconia (ZrO2) powder is a kind of biocompatible material, red
      phosphorus can be used to produce safety matches, organophosphorous pesticide and
      phosphor bronze, and the produced N2 might be collected and used as a protective
      gas or be converted into liquid nitrogen for other purposes.

PMID- 29026177
TI  - Divergent drivers of the spatial and temporal variations of cropland carbon
      transfer in Liaoning province, China.
AB  - Spatial and temporal variations are important points of focus in ecological
      research. Analysing their differences improves our understanding on the
      variations of ecological phenomena. Using data from the Liaoning Statistical
      Yearbook, we investigated the spatial and temporal variations of cropland carbon
      transfer (CCT), an important ecological phenomenon in quantifying the regional
      carbon budget, in particular, the influencing factors and difference. The results
      showed that, from 1992 to 2014, the average CCT in Liaoning province was 18.56
      TgC yr-1 and decreased from northwest to southeast. CCT spatial variation was
      primarily affected by the ratio of planting area to regional area (RPR) via its
      effect on the magnitude of carbon transfer (MCT), which depended mainly on
      fertilizer usage per area (FUA). From 1992 to 2014, CCT exhibited a significantly
      increasing trend with a rate of 0.48 TgC yr-1. The inter-annual variation of CCT
      was dominated by carbon transfer per planting area (CTP) through its effect on
      MCT, which significantly correlated with FUA but showed no significant
      correlation with climatic factors. Therefore, the factors affecting the spatial
      variation of CCT differed from those that affected its inter-annual variation,
      indicating that the spatial and temporal variations of ecological phenomena were
      affected by divergent factors.

PMID- 29026178
TI  - Erratum: One-month spaceflight compromises the bone microstructure, tissue-level
      mechanical properties, osteocyte survival and lacunae volume in mature mice
      skeletons.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29026176
TI  - Primary Astrocytic Tumours and Paired Recurrences have Similar Biological
      Features in IDH1, TP53 and TERTp Mutation and MGMT, ATRX Loss.
AB  - Astrocytic tumours are the most common type of primary malignant brain tumour.
      Most astrocytic tumours will recur at some point after surgery. Currently, the
      combination of radiotherapy and chemotherapy does not prevent the recurrence of
      astrocytic tumours. In this study, we investigated the consistency in isocitrate
      dehydrogenase 1 (IDH1), tumour protein p53 (TP53) and telomerase reverse
      transcriptase promoter (TERTp) mutations during astrocytic tumour recurrence. We
      also evaluated the protein loss of O-6-methylguanine-DNA methyltransferase (MGMT)
      and alpha-thalassemia/mental retardation, X-linked (ATRX) during disease
      recurrence. We then determined the prognostic significance of these findings in
      terms of progression-free survival (PFS) using Kaplan-Meier analysis and Cox
      regression models. Our results showed that in most cases, IDH1, TP53 and TERTp
      mutation status and MGMT and ATRX protein expression levels were stable during
      recurrence, which may indicate that these alterations occurred early in
      astrocytic tumour development. Furthermore, in IDH1 wild type group, the patients
      who were negative for MGMT and had a low Ki67 index showed a longer PFS.
      Therefore, we suggest that IDH1 mutation combined with MGMT expression level and
      Ki67 index might be an effective biomarker panel for evaluating the PFS of
      patients with astrocytic tumours.

PMID- 29026179
TI  - Effects of Prenatal Phthalate Exposure on Thyroid Hormone Concentrations
      Beginning at The Embryonic Stage.
AB  - Limited studies have consistently shown an association of phthalates exposure
      with thyroid hormones (THs) in pregnant women. However, it remains unknown on
      which specific phthalates can affect THs and whether any effects could differ by
      gestational age. In the present study, we investigated associations between serum
      concentrations of phthalate monoesters [monoethyl phthalate (MEP), mono-(n + iso)
      butyl phthalate (MBP) and mono(2-ethylhexyl) phthalate (MEHP)] and THs [thyroid
      stimulating hormone (TSH), total thyroxine (TT4) and free thyroxine (FT4)] in
      Chinese pregnant women. 1,397 women were recruited from the China-Anhui Birth
      Cohort. Maternal serum samples were collected and used to measure phthalate
      metabolites and THs. Covariate-adjusted linear regression analyses showed that
      natural log (Ln)-transferred concentrations of MBP and LnMEHP were negatively
      associated with TT4 (beta = -0.277 and -0.461, respectively; p < 0.001).
      Stratification analyses by gestational weeks showed significant associations of
      LnMBP and LnMEHP with TT4 in gestational weeks 5 to 8, 9 to 12, and 13 to 20. Our
      findings suggest an association of serum phthalates with lower TT4. The influence
      of MBP and MEHP on TT4 concentrations throughout the early pregnancy may begin
      from the embryonic stage (gestational weeks 5 to 8).

PMID- 29026180
TI  - Ultraintense UV emission from ZnO-sheathed ZnS nanorods.
AB  - Short-wavelength luminescence is essential for high-performance optoelectronic
      device applications. There have been efforts to obtain intense ultraviolet (UV)
      emission by encapsulating ZnO one-dimensional (1D) nanostructures with materials
      such as ZnS. However, the encapsulation of ZnS 1D nanostructures with ZnO has not
      been reported. In this paper, we report ultraintense UV emission from ZnS
      nanorods coated with ZnO, i.e., ZnS-core/ZnO-shell nanorods. UV emission from the
      ZnS-core/ZnO-shell nanorods was much more intense than that obtained from the
      extensively studied ZnO-core/ZnS-shell nanorods. The highest intensity of the
      near-band-edge emission from the ZnS-core/ZnO-shell nanorods was obtained with a
      ZnO shell layer thickness of 35 nm, which is ~16 times higher than that of
      pristine ZnS nanorods. Moreover, the deep level (DL) emission was suppressed
      completely. The substantial enhancement of the UV emission from the ZnS nanorods
      and the complete suppression of the DL emission by ZnO sheathing can be
      rationalized by combining the following four effects: the reinforcement of the UV
      emission by the overlap of the UV emissions from the ZnS core and ZnO shell,
      enhancement of the emission from the ZnO shell by the carrier transfer from the
      ZnS core to the ZnO shell, suppression of the capture of carriers by the surface
      states on the ZnS surface, and suppression of the visible emission and
      nonradiative recombination in ZnS.

PMID- 29026182
TI  - Effects of disorder induced by heavy-ion irradiation on (Ba1-x K x )Fe2As2 single
      crystals, within the three-band Eliashberg s+/- wave model.
AB  - One of the open issues concerning iron-based superconductors is whether the s+/-
      wave model is able to account for the overall effects of impurity scattering,
      including the low rate of decrease of the critical temperature with the impurity
      concentration. Here we investigate Ba1-x K x Fe2As2 crystals where disorder is
      introduced by Au-ion irradiation. Critical temperature, T c , and London
      penetration depth, lambda L , were measured by a microwave resonator technique,
      for different values of the irradiation fluence. We compared experimental data
      with calculations made on the basis of the three-band Eliashberg equations,
      suitably accounting for the impurity scattering. We show that this approach is
      able to explain in a consistent way the effects of disorder both on T c and on
      lambda L (T), within the s+/- wave model. In particular, a change of curvature in
      the low-temperature lambda L (T) curves for the most irradiated crystals is
      fairly well reproduced.

PMID- 29026181
TI  - Social support and mental health in late adolescence are correlated for genetic,
      as well as environmental, reasons.
AB  - Late adolescence is a crucial, but underexplored, developmental stage with
      respect to the aetiology of social support. These individuals are experiencing
      many major life changes and social support can help them adjust to the associated
      environmental stressors of this time. Using 1,215 18-year-old twin pairs from the
      Twins Early Development Study, we collected measures of two indices of support:
      support quality and support quantity, as well as wellbeing and depression. Both
      support indices were moderately heritable (55% and 49%, respectively), an
      interesting finding given the many environmental changes that late adolescents
      are encountering that could be environmentally altering their social network
      structures. Finding a genetic influence on support suggests the presence of gene
      environment correlation whereby individuals create and perceive their supportive
      environment based upon their genetic predispositions. Shared genetic influences
      mediated the moderate phenotypic correlation (mean r = 0.46) between support and
      mental health. Genetic correlations were higher between support quality and
      mental health (mean rA = 0.75), than between support quantity and mental health
      (mean rA = 0.54), reflecting the phenotypic pattern. This suggests that
      interventions should focus more on making late adolescents aware of the support
      quality around them than encouraging them to increase their social network size.

PMID- 29026183
TI  - Developmental Emergence of Sparse Coding: A Dynamic Systems Approach.
AB  - During neocortical development, network activity undergoes a dramatic transition
      from largely synchronized, so-called cluster activity, to a relatively sparse
      pattern around the time of eye-opening in rodents. Biophysical mechanisms
      underlying this sparsification phenomenon remain poorly understood. Here, we
      present a dynamic systems modeling study of a developing neural network that
      provides the first mechanistic insights into sparsification. We find that the
      rest state of immature networks is strongly affected by the dynamics of a
      transient, unstable state hidden in their firing activities, allowing these
      networks to either be silent or generate large cluster activity. We address how,
      and which, specific developmental changes in neuronal and synaptic parameters
      drive sparsification. We also reveal how these changes refine the information
      processing capabilities of an in vivo developing network, mainly by showing a
      developmental reduction in the instability of network's firing activity, an
      effective availability of inhibition-stabilized states, and an emergence of
      spontaneous attractors and state transition mechanisms. Furthermore, we
      demonstrate the key role of GABAergic transmission and depressing glutamatergic
      synapses in governing the spatiotemporal evolution of cluster activity. These
      results, by providing a strong link between experimental observations and model
      behavior, suggest how adult sparse coding networks may emerge developmentally.

PMID- 29026184
TI  - Research attitudes and perceived barriers to conducting research among
      ophthalmology trainees.

PMID- 29026185
TI  - Simple fixation and removal of dacryocystorhinostomy tube.

PMID- 29026186
TI  - About bariatric surgery and diabetic retinopathy; the debate continues.

PMID- 29026188
TI  - Practitioner evaluation of an online oral health and risk assessment tool for
      young patients.
AB  - Aim To test the validity and acceptability of an online oral health assessment
      and biofeedback tool for young patients (under 17) for use in general dental
      practice.Methods A convenience sample of thirteen practitioners were recruited to
      test the functionality of a novel version of the Denplan PreViser Patient
      Assessment tool (DEPPA) developed for young patients (YDEPPA). Dentists who had
      completed eight or more assessments during a one month window were sent a link to
      an online feedback survey, comprising eight statements about YDEPPA, with scoring
      options of 0-10, where a score of 10 indicated complete agreement with the
      relevant questions. Verbatim comments were encouraged. The clinical data
      submitted were held in a central database in an encrypted format so that only the
      user practice could identify individual patients.Results Twelve practitioners
      completed eight or more assessments and were included in the survey. A total of
      175 patient assessments were received. Ten practitioners completed the on-line
      survey. The statement 'YDEPPA produces a valid measurement of each patient's oral
      health' received an average feedback score of 8.8. The statement 'The full YDEPPA
      report is a valuable communication aid' received a score of 9.6. Feedback was
      generally very positive with all scores >8.2. Constructive critical feedback was
      received for the caries risk aspect of the YDEPPA protocol, with suggestions made
      for improving objectivity of data inputs. Eighty-one percent of the verbatim
      comments received were positive.Conclusions Once the caries risk issues raised by
      pilot dentists have been addressed, YDEPPA appears suitable as a pragmatic
      analytical and biofeedback tool for use in general dental practice to assess the
      oral health of young patients, and to facilitate education and engagement of
      young patients and their parents/carers in positive health behaviours.

PMID- 29026187
TI  - Comment on: 'One-year real-world outcomes in patients receiving fixed-dosing
      aflibercept for neovascular age-related macular degeneration'.

PMID- 29026189
TI  - Sustainability and Transformation Partnerships: What are they and how do they
      affect dentistry?
AB  - Sustainability and Transformation Partnerships or 'STPs' have been formed from
      NHS and social care providers, commissioners, and local councils in 44 areas
      covering the whole of England to improve the care they provide. Proposals, known
      as 'Sustainability and Transformation Plans' have been developed that address the
      needs of the whole population of each area, rather than the needs of each
      individual organisation. STPs are fundamental to how care will be delivered and
      commissioned in the future and have recently been portrayed in the media as the
      vehicle for cuts to NHS services. Here we explore how accurate this is, how STPs
      vary in different areas, and the opportunities they present for dentistry to
      become more integrated with other NHS services.

PMID- 29026190
TI  - Growth hormone secretagogues hexarelin and JMV2894 protect skeletal muscle from
      mitochondrial damages in a rat model of cisplatin-induced cachexia.
AB  - Chemotherapy can cause cachexia, which consists of weight loss associated with
      muscle atrophy. The exact mechanisms underlying this skeletal muscle toxicity are
      largely unknown and co-therapies to attenuate chemotherapy-induced side effects
      are lacking. By using a rat model of cisplatin-induced cachexia, we here
      characterized the mitochondrial homeostasis in tibialis anterior cachectic muscle
      and evaluated the potential beneficial effects of the growth hormone
      secretagogues (GHS) hexarelin and JMV2894 in this setting. We found that
      cisplatin treatment caused a decrease in mitochondrial biogenesis (PGC-1alpha,
      NRF-1, TFAM, mtDNA, ND1), mitochondrial mass (Porin and Citrate synthase
      activity) and fusion index (MFN2, Drp1), together with changes in the expression
      of autophagy-related genes (AKT/FoxO pathway, Atg1, Beclin1, LC3AII, p62) and
      enhanced ROS production (PRX III, MnSOD). Importantly, JMV2894 and hexarelin are
      capable to antagonize this chemotherapy-induced mitochondrial dysfunction. Thus,
      our findings reveal a key-role played by mitochondria in the mechanism
      responsible for GHS beneficial effects in skeletal muscle, strongly indicating
      that targeting mitochondrial dysfunction might be a promising area of research in
      developing therapeutic strategies to prevent or limit muscle wasting in cachexia.

PMID- 29026191
TI  - Mechanisms involved in the triggering of neutrophil extracellular traps (NETs) by
      Candida glabrata during planktonic and biofilm growth.
AB  - Candida spp. adhere to medical devices, such as catheters, forming drug-tolerant
      biofilms that resist killing by the immune system. Little is known about how C.
      glabrata, an emerging pathogen, resists attack by phagocytes. Here we show that
      upon encounter with planktonic (non-biofilm) C. glabrata, human neutrophils
      initially phagocytose the yeast and subsequently release neutrophil extracellular
      traps (NETs), complexes of DNA, histones, and proteins capable of inhibiting
      fungal growth and dissemination. When exposed to C. glabrata biofilms,
      neutrophils also release NETs, but significantly fewer than in response to
      planktonic cells. Impaired killing of biofilm parallels the decrease in NET
      production. Compared to biofilm, neutrophils generate higher levels of reactive
      oxygen species (ROS) when presented with planktonic organisms, and pharmacologic
      inhibition of NADPH-oxidase partially impairs NET production. In contrast,
      inhibition of phagocytosis nearly completely blocks NET release to both biofilm
      and planktonic organisms. Imaging of the host response to C. glabrata in a rat
      vascular model of infection supports a role for NET release in vivo. Taken
      together, these findings show that C. glabrata triggers NET release. The
      diminished NET response to C. glabrata biofilms likely contributes to the
      resilience of these structured communities to host defenses.

PMID- 29026192
TI  - Enhancing the sialylation of recombinant EPO produced in CHO cells via the
      inhibition of glycosphingolipid biosynthesis.
AB  - Sialylation regulates the in vivo half-life of recombinant therapeutic
      glycoproteins, affecting their therapeutic efficacy. Levels of the precursor
      molecule cytidine monophospho-N-acetylneuraminic acid (CMP-Neu5Ac) are considered
      a limiting factor in the sialylation of glycoproteins. Here, we show that by
      reducing the amount of intracellular CMP-Neu5Ac consumed for glycosphingolipid
      (GSL) biosynthesis, we can increase the sialylation of recombinant human
      erythropoietin (rhEPO) produced in CHO cells. Initially, we found that treating
      CHO cells with a potent inhibitor of GSL biosynthesis increases the sialylation
      of the rhEPO they produce. Then, we established a stable CHO cell line that
      produces rhEPO in the context of repression of the key GSL biosynthetic enzyme
      UDP-glucose ceramide glucosyltransferase (UGCG). These UGCG-depleted cells show
      reduced levels of gangliosides and significantly elevated levels of rhEPO
      sialylation. Upon further analysis of the resulting N-glycosylation pattern, we
      discovered that the enhanced rhEPO sialylation could be attributed to a decrease
      in neutral and mono-sialylated N-glycans and an increase in di-sialylated N
      glycans. Our results suggest that the therapeutic efficacy of rhEPO produced in
      CHO cells can be improved by shunting intracellular CMP-Neu5Ac away from GSL
      biosynthesis and toward glycoprotein sialylation.

PMID- 29026193
TI  - Biomarker-indicated extent of oxidation of plant-derived organic carbon (OC) in
      relation to geomorphology in an arsenic contaminated Holocene aquifer, Cambodia.
AB  - The poisoning of rural populations in South and Southeast Asia due to high
      groundwater arsenic concentrations is one of the world's largest ongoing natural
      disasters. It is important to consider environmental processes related to the
      release of geogenic arsenic, including geomorphological and organic geochemical
      processes. Arsenic is released from sediments when iron-oxide minerals, onto
      which arsenic is adsorbed or incorporated, react with organic carbon (OC) and the
      OC is oxidised. In this study we build a new geomorphological framework for
      Kandal Province, a highly studied arsenic affected region of Cambodia, and tie
      this into wider regional environmental change throughout the Holocene. Analyses
      shows that the concentration of OC in the sediments is strongly inversely
      correlated to grainsize. Furthermore, the type of OC is also related to grain
      size with the clay containing mostly (immature) plant derived OC and sand
      containing mostly thermally mature derived OC. Finally, analyses indicate that
      within the plant derived OC relative oxidation is strongly grouped by
      stratigraphy with the older bound OC more oxidised than younger OC.

PMID- 29026194
TI  - The equivalent internal orientation and position noise for contour integration.
AB  - Contour integration is the joining-up of local responses to parts of a contour
      into a continuous percept. In typical studies observers detect contours formed of
      discrete wavelets, presented against a background of random wavelets. This
      measures performance for detecting contours in the limiting external noise that
      background provides. Our novel task measures contour integration without
      requiring any background noise. This allowed us to perform noise-masking
      experiments using orientation and position noise. From these we measure the
      equivalent internal noise for contour integration. We found an orientation noise
      of 6 degrees  and position noise of 3 arcmin. Orientation noise was 2.6x higher
      in contour integration compared to an orientation discrimination control task.
      Comparing against a position discrimination task found position noise in contours
      to be 2.4x lower. This suggests contour integration involves intermediate
      processing that enhances the quality of element position representation at the
      expense of element orientation. Efficiency relative to the ideal observer was
      lower for the contour tasks (36% in orientation noise, 21% in position noise)
      compared to the controls (54% and 57%).

PMID- 29026196
TI  - Work and information from thermal states after subtraction of energy quanta.
AB  - Quantum oscillators prepared out of thermal equilibrium can be used to produce
      work and transmit information. By intensive cooling of a single oscillator, its
      thermal energy deterministically dissipates to a colder environment, and the
      oscillator substantially reduces its entropy. This out-of-equilibrium state
      allows us to obtain work and to carry information. Here, we propose and
      experimentally demonstrate an advanced approach, conditionally preparing more
      efficient out-of-equilibrium states only by a weak dissipation, an inefficient
      quantum measurement of the dissipated thermal energy, and subsequent triggering
      of that states. Although it conditionally subtracts the energy quanta from the
      oscillator, average energy grows, and second-order correlation function
      approaches unity as by coherent external driving. On the other hand, the Fano
      factor remains constant and the entropy of the subtracted state increases, which
      raise doubts about a possible application of this approach. To resolve it, we
      predict and experimentally verify that both available work and transmitted
      information can be conditionally higher in this case than by arbitrary cooling or
      adequate thermal heating up to the same average energy. It qualifies the
      conditional procedure as a useful source for experiments in quantum information
      and thermodynamics.

PMID- 29026195
TI  - Characterization of Fluorescein Arsenical Hairpin (FlAsH) as a Probe for Single
      Molecule Fluorescence Spectroscopy.
AB  - In recent years, new labelling strategies have been developed that involve the
      genetic insertion of small amino-acid sequences for specific attachment of small
      organic fluorophores. Here, we focus on the tetracysteine FCM motif
      (FLNCCPGCCMEP), which binds to fluorescein arsenical hairpin (FlAsH), and the
      ybbR motif (TVLDSLEFIASKLA) which binds fluorophores conjugated to Coenzyme A
      (CoA) via a phosphoryl transfer reaction. We designed a peptide containing both
      motifs for orthogonal labelling with FlAsH and Alexa647 (AF647). Molecular
      dynamics simulations showed that both motifs remain solvent-accessible for
      labelling reactions. Fluorescence spectra, correlation spectroscopy and
      anisotropy decay were used to characterize labelling and to obtain photophysical
      parameters of free and peptide-bound FlAsH. The data demonstrates that FlAsH is a
      viable probe for single-molecule studies. Single-molecule imaging confirmed dual
      labeling of the peptide with FlAsH and AF647. Multiparameter single-molecule
      Forster Resonance Energy Transfer (smFRET) measurements were performed on freely
      diffusing peptides in solution. The smFRET histogram showed different peaks
      corresponding to different backbone and dye orientations, in agreement with the
      molecular dynamics simulations. The tandem of fluorophores and the labelling
      strategy described here are a promising alternative to bulky fusion fluorescent
      proteins for smFRET and single-molecule tracking studies of membrane proteins.

PMID- 29026197
TI  - Differences in Tribological Behaviors upon Switching Fixed and Moving Materials
      of Tribo-pairs including Metal and Polymer.
AB  - The coefficient of friction (COF) between two materials is usually believed to be
      an intrinsic property of the materials themselves. In this study, metals of
      stainless steel (304) and brass (H62), and polymers of polypropylene (PP) and
      polytetrafluoroethylene (PTFE) were tested on a standard ball-on-three-plates
      test machine. Significantly different tribological behaviors were observed when
      fixed and moving materials of tribo-pairs (metal/polymer) were switched. As an
      example, under the same applied load and rotating speed, the COF (0.49) between a
      rotating PP ball and three fixed H62 plates was approximately 2.3 times higher
      than that between switched materials of tribo-pairs. Meanwhile, the COF between
      H62 and PTFE was relatively stable. The unexpected tribological behaviors were
      ascribed to the thermal and mechanical properties of tribo-pairs. Theoretical
      analysis revealed that the differences in the maximum local temperature between
      switching the fixed and moving materials of tribo-pairs were consistent with the
      differences in the tested COF. This result indicated the precise prediction of
      the COF of two materials is complexcity, and that thermal and mechanical
      properties should be properly considered in designing tribo-pairs, because these
      properties may significantly affect tribological performance.

PMID- 29026198
TI  - Ctbp2-mediated beta-catenin regulation is required for exit from pluripotency.
AB  - The canonical Wnt pathway is critical for embryonic stem cell (ESC) pluripotency
      and aberrant control of beta-catenin leads to failure of exit from pluripotency
      and lineage commitments. Hence, maintaining the appropriate level of beta-catenin
      is important for the decision to commit to the appropriate lineage. However, how
      beta-catenin links to core transcription factors in ESCs remains elusive. C
      terminal-binding protein (CtBP) in Drosophila is essential for Wnt-mediated
      target gene expression. In addition, Ctbp acts as an antagonist of beta
      catenin/TCF activation in mammals. Recently, Ctbp2, a core Oct4-binding protein
      in ESCs, has been reported to play a key role in ESC pluripotency. However, the
      significance of the connection between Ctbp2 and beta-catenin with regard to ESC
      pluripotency remains elusive. Here, we demonstrate that C-terminal-binding
      protein 2 (Ctbp2) associates with major components of the beta-catenin
      destruction complex and limits the accessibility of beta-catenin to core
      transcription factors in undifferentiated ESCs. Ctbp2 knockdown leads to
      stabilization of beta-catenin, which then interacts with core pluripotency
      maintaining factors that are occupied by Ctbp2, leading to incomplete exit from
      pluripotency. These findings suggest a suppressive function for Ctbp2 in reducing
      the protein level of beta-catenin, along with priming its position on core
      pluripotency genes to hinder beta-catenin deposition, which is central to
      commitment to the appropriate lineage.

PMID- 29026199
TI  - Probiotic supplementation in preterm infants does not affect the risk of
      retinopathy of prematurity: a meta-analysis of randomized controlled trials.
AB  - Retinopathy of prematurity (ROP) is a vascular disorder of the developing retina
      in preterm infants and is a leading cause of childhood blindness. Perinatal
      infection plays a pathogenic role in ROP. Probiotic supplementation reduces the
      risk of late onset sepsis (LOS) in preterm infants but it remains to be
      determined whether this reduction translates into a reduction of other
      complications. We conducted a systematic review and meta-analysis to evaluate the
      possible role of probiotics in altering the risk of ROP. Eleven randomized
      controlled trials (4250 infants; probiotics: 2121) were included in the meta
      analysis that showed a significantly decreased rate of LOS with a risk ratio (RR)
      of 0.807 and a 95% confidence interval (CI) of 0.705 to 0.924 (P = 0.010; fixed
      effects model) but could not demonstrate a significant effect of probiotics on
      any stage ROP (RR 1.053, 95% CI 0.903 to 1.228, P = 0.508, 4 studies), or severe
      ROP (RR 0.841, 95% CI 0.666 to 1.063, P = 0.148, 9 studies). Meta-regression did
      not show any significant association between the RR for LOS and the RR for severe
      ROP. In conclusion, our results suggest that infection prevention by probiotics
      does not affect the risk of developing ROP in preterm infants.

PMID- 29026200
TI  - Simultaneous quantification of nine aconitum alkaloids in Aconiti Lateralis Radix
      Praeparata and related products using UHPLC-QQQ-MS/MS.
AB  - Aconiti Lateralis Radix Praeparata (Fuzi) is obtained from processed daughter
      roots of Aconitum carmichaeli, a toxic plant with a high medical value well known
      in Chinese medicine. In addition to the known toxic alkaloids (aconitine,
      mesaconitine, and hypaconitine) and bioactive alkaloids (benzoylaconine,
      benzoylmesaconine, and benzoylhypaconine), three rarely found alkaloids have been
      previously reported in Fuzi, i.e., yunaconitine, 8-deacetyl-yunaconitine, and
      crassicauline A, and they were reported in recent years to cause potential risk
      to patients who took Fuzi or related products. To better control the quality of
      this herb and its related products and ensure safe use, developing a method to
      simultaneously determine these 9 alkaloids is important. In this research,
      sensitive and accurate ultra-high-performance liquid chromatography coupled with
      triple quadrupole mass spectrometry method was established and used to examine 51
      Fuzi and 27 Fuzi-containing products. Unexpectedly, 8-deacetyl-yunaconitine was
      detected in 17 Fuzi samples (33.3%) and 3 Fuzi-containing products (11.1%);
      yunaconitine in 10 Fuzi samples (19.6%) and 10 Fuzi-containing products (37.0%);
      and crassicauline A in 3 Fuzi samples (5.8%). Industry and clinics should be
      aware of the unusually high detection rate of these three toxic alkaloids in the
      Fuzi herb and its related products and take the necessary precautions to protect
      patients from any potential risk.

PMID- 29026202
TI  - Loss of ABHD5 promotes the aggressiveness of prostate cancer cells.
AB  - The accumulation of neutral lipids in intracellular lipid droplets has been
      associated with the formation and progression of many cancers, including prostate
      cancer (PCa). Alpha-beta Hydrolase Domain Containing 5 (ABHD5) is a key regulator
      of intracellular neutral lipids that has been recently identified as a tumor
      suppressor in colorectal cancer, yet its potential role in PCa has not been
      investigated. Through mining publicly accessible PCa gene expression datasets, we
      found that ABHD5 gene expression is markedly decreased in metastatic castration
      resistant PCa (mCRPC) samples. We further demonstrated that RNAi-mediated ABHD5
      silencing promotes, whereas ectopic ABHD5 overexpression inhibits, the invasion
      and proliferation of PCa cells. Mechanistically, we found that ABHD5 knockdown
      induces epithelial to mesenchymal transition, increasing aerobic glycolysis by
      upregulating the glycolytic enzymes hexokinase 2 and phosphofrucokinase, while
      decreasing mitochondrial respiration by downregulating respiratory chain
      complexes I and III. Interestingly, knockdown of ATGL, the best-known molecular
      target of ABHD5, impeded the proliferation and invasion, suggesting an ATGL
      independent role of ABHD5 in modulating PCa aggressiveness. Collectively, these
      results provide evidence that ABHD5 acts as a metabolic tumor suppressor in PCa
      that prevents EMT and the Warburg effect, and indicates that ABHD5 is a potential
      therapeutic target against mCRPC, the deadly aggressive PCa.

PMID- 29026203
TI  - Immunotherapy: When viruses attack.

PMID- 29026201
TI  - Dual contribution of TRPV4 antagonism in the regulatory effect of vasoinhibins on
      blood-retinal barrier permeability: diabetic milieu makes a difference.
AB  - Breakdown of the blood-retinal barrier (BRB), as occurs in diabetic retinopathy
      and other chronic retinal diseases, results in vasogenic edema and neural tissue
      damage, causing vision loss. Vasoinhibins are N-terminal fragments of prolactin
      that prevent BRB breakdown during diabetes. They modulate the expression of some
      transient receptor potential (TRP) family members, yet their role in regulating
      the TRP vanilloid subtype 4 (TRPV4) remains unknown. TRPV4 is a calcium-permeable
      channel involved in barrier permeability, which blockade has been shown to
      prevent and resolve pulmonary edema. We found TRPV4 expression in the endothelium
      and retinal pigment epithelium (RPE) components of the BRB, and that TRPV4
      selective antagonists (RN-1734 and GSK2193874) resolve BRB breakdown in diabetic
      rats. Using human RPE (ARPE-19) cell monolayers and endothelial cell systems, we
      further observed that (i) GSK2193874 does not seem to contribute to the
      regulation of BRB and RPE permeability by vasoinhibins under diabetic or
      hyperglycemic-mimicking conditions, but that (ii) vasoinhibins can block TRPV4 to
      maintain BRB and endothelial permeability. Our results provide important insights
      into the pathogenesis of diabetic retinopathy that will further guide us toward
      rationally-guided new therapies: synergistic combination of selective TRPV4
      blockers and vasoinhibins can be proposed to mitigate diabetes-evoked BRB
      breakdown.

PMID- 29026205
TI  - Non-small cell lung cancer: Where there's smoke...

PMID- 29026206
TI  - Genome-wide association studies of cancer: current insights and future
      perspectives.
AB  - Genome-wide association studies (GWAS) provide an agnostic approach for
      investigating the genetic basis of complex diseases. In oncology, GWAS of nearly
      all common malignancies have been performed, and over 450 genetic variants
      associated with increased risks have been identified. As well as revealing novel
      pathways important in carcinogenesis, these studies have shown that common
      genetic variation contributes substantially to the heritable risk of many common
      cancers. The clinical application of GWAS is starting to provide opportunities
      for drug discovery and repositioning as well as for cancer prevention. However,
      deciphering the functional and biological basis of associations is challenging
      and is in part a barrier to fully unlocking the potential of GWAS.

PMID- 29026207
TI  - Citrus peel essential oil nanoformulations to control the tomato borer, Tuta
      absoluta: chemical properties and biological activity.
AB  - The repeated use of conventional synthetic pesticides in crop protection leads to
      resistance development by pests along with a negative impact on the environment,
      particularly non-target arthropods. Plant-derived active compounds, such as
      essential oils (EOs), play a key role in sustainably controlling pests. The
      lethal and sublethal activity of citrus peel EOs as emulsions and included in
      polyethylene glycol (PEG) nanoparticles (EO-NPs) was determined against the
      invasive tomato pest Tuta absoluta. Their effects on the plants were also
      assessed. The results showed an overall good insecticidal activity of the
      compounds tested, with a higher mortality through contact on eggs and larvae by
      EO emulsions and through ingestion on larvae by EO-NPs. The nanoformulation also
      significantly reduced the visible toxic effects on the plants. The data collected
      suggest that these natural compounds, especially when nanoformulated, could be
      successfully used in integrated pest management programs for T. absoluta.

PMID- 29026208
TI  - Targetable fusions of the FRK tyrosine kinase in ALK-negative anaplastic large
      cell lymphoma.

PMID- 29026204
TI  - Engineering and physical sciences in oncology: challenges and opportunities.
AB  - The principles of engineering and physics have been applied to oncology for
      nearly 50 years. Engineers and physical scientists have made contributions to all
      aspects of cancer biology, from quantitative understanding of tumour growth and
      progression to improved detection and treatment of cancer. Many early efforts
      focused on experimental and computational modelling of drug distribution, cell
      cycle kinetics and tumour growth dynamics. In the past decade, we have witnessed
      exponential growth at the interface of engineering, physics and oncology that has
      been fuelled by advances in fields including materials science, microfabrication,
      nanomedicine, microfluidics, imaging, and catalysed by new programmes at the
      National Institutes of Health (NIH), including the National Institute of
      Biomedical Imaging and Bioengineering (NIBIB), Physical Sciences in Oncology, and
      the National Cancer Institute (NCI) Alliance for Nanotechnology. Here, we review
      the advances made at the interface of engineering and physical sciences and
      oncology in four important areas: the physical microenvironment of the tumour and
      technological advances in drug delivery; cellular and molecular imaging; and
      microfluidics and microfabrication. We discussthe research advances,
      opportunities and challenges for integrating engineering and physical sciences
      with oncology to develop new methods to study, detect and treat cancer, and we
      also describe the future outlook for these emerging areas.

PMID- 29026210
TI  - Bispecific antibody pipeline moves beyond oncology.
AB  - This corrects the article DOI: 10.1038/nrd.2017.187.

PMID- 29026209
TI  - WD40 repeat domain proteins: a novel target class?
AB  - Antagonism of protein-protein interactions (PPIs) with small molecules is
      becoming more feasible as a therapeutic approach. Successful PPI inhibitors tend
      to target proteins containing deep peptide-binding grooves or pockets rather than
      the more common large, flat protein interaction surfaces. Here, we review one of
      the most abundant PPI domains in the human proteome, the WD40 repeat (WDR)
      domain, which has a central peptide-binding pocket and is a member of the beta
      propeller domain-containing protein family. Recently, two WDR domain-containing
      proteins, WDR5 and EED, as well as other beta-propeller domains have been
      successfully targeted by potent, specific, cell-active, drug-like chemical
      probes. Could WDR domains be a novel target class for drug discovery? Although
      the research is at an early stage and therefore not clinically validated,
      cautious optimism is justified, as WDR domain-containing proteins are involved in
      multiple disease-associated pathways. The druggability and structural diversity
      of WDR domain binding pockets suggest that understanding how to target this
      prevalent domain class will open up areas of disease biology that have so far
      resisted drug discovery efforts.

PMID- 29026212
TI  - Infrared light field imaging system free of fixed-pattern noise.
AB  - Digital photonic sensors have greatly evolved to maximize sensitivity and
      spatial, spectral, and temporal imaging resolution. For low-energy photons, new
      designs have generated new types of noise that degrade the formed-image signal-to
      noise ratio to values lower than 1. Fixed-pattern noise (FPN), which is produced
      by the non-uniform focal-plane-array optoelectronics response, is an ill-posed
      problem in infrared and hyperspectral imaging science. Here, we experimentally
      show that the FPN behaves as an object at a depth of infinity when a light field
      is captured by an imaging system. The proposed method is based on the capture of
      the light field of a scene and digital refocusing to any nearby objects in the
      scene. Unlike standard techniques for FPN reduction, our method does not require
      knowledge of the physical parameters of the optoelectronic transducer, the motion
      scene, or the presence of off-line blackbody sources. The ability of the proposed
      method to reduce FPN is measured by evaluating the structural similarity (SSIM)
      index employing a blackbody-based FPN reduction technique as a reference. This
      new interpretation of the FPN opens avenues to create new cameras for low-energy
      photons with the ability to perform denoising by digital refocusing.

PMID- 29026211
TI  - Legacy data sharing to improve drug safety assessment: the eTOX project.
AB  - The sharing of legacy preclinical safety data among pharmaceutical companies and
      its integration with other information sources offers unprecedented opportunities
      to improve the early assessment of drug safety. Here, we discuss the experience
      of the eTOX project, which was established through the Innovative Medicines
      Initiative to explore this possibility.

PMID- 29026213
TI  - Genomic divergence within non-photosynthetic cyanobacterial endosymbionts in
      rhopalodiacean diatoms.
AB  - Organelle acquisitions via endosymbioses with prokaryotes were milestones in the
      evolution of eukaryotes. Still, quite a few uncertainties have remained for the
      evolution in the early stage of organellogenesis. In this respect, rhopalodiacean
      diatoms and their obligate cyanobacterial endosymbionts, called spheroid bodies,
      are emerging as new models for the study of organellogenesis. The genome for the
      spheroid body of Epithemia turgida, a rhopalodiacean diatom, has unveiled its
      unique metabolic nature lacking the photosynthetic ability. Nevertheless, the
      genome sequence of a spheroid body from a single lineage may not be sufficient to
      depict the evolution of these cyanobacterium-derived intracellular structures as
      a whole. Here, we report on the complete genome for the spheroid body of
      Rhopalodia gibberula, a lineage distinct from E. turgida, of which genome has
      been fully determined. Overall, features in genome structure and metabolic
      capacity, including a lack of photosynthetic ability, were highly conserved
      between the two spheroid bodies. However, our comparative genomic analyses
      revealed that the genome of the R. gibberula spheroid body exhibits a lower non
      synonymous substitution rate and a slower progression of pseudogenisation than
      those of E. turgida, suggesting that a certain degree of diversity exists amongst
      the genomes of obligate endosymbionts in unicellular eukaryotes.

PMID- 29026215
TI  - Journals should no longer accept 'obesity paradox' articles.

PMID- 29026214
TI  - Treatment with the TGF-b superfamily cytokine MIC-1/GDF15 reduces the adiposity
      and corrects the metabolic dysfunction of mice with diet-induced obesity.
AB  - OBJECTIVES: To test the potential efficacy of recombinant macrophage inhibitory
      cytokine-1 (MIC-1/GDF15) as an obesity therapeutic. METHODS: Male C57BL/6 J mice,
      either fed on normal chow or high-fat diet for 16 weeks to induce diet-induced
      obesity, were infused with either recombinant MIC-1/GDF15 or vehicle for 34 days
      by osmotic minipump. During the experimental period metabolic parameters were
      measured. Blood and tissue were collected for analysis of inflammatory markers.
      RESULTS: MIC-1/GDF15 decreased food intake and body weight of high-fat-fed and
      chow-fed mice compared with their vehicle-treated control mice. MIC-1/GDF15
      reduced body weight, accompanied by greater reduction in fat mass in high-fat-fed
      mice compared to its effect on chow-fed mice. Further, whilst MIC-1/GDF15-treated
      chow-fed mice lost lean as well as fat mass, MIC-1/GDF15-treated high-fat-fed
      mice lost fat mass alone. This reduction in body weight and adiposity was due
      largely to reduced food intake, but MIC-1/GDF15-treated high-fat-fed mice also
      displayed increased energy expenditure that may be due to increased
      thermogenesis. MIC-1/GDF15-treated high-fat-fed mice also had higher circulating
      level of adiponectin and lower tissue expression, and circulating levels of
      leptin and inflammatory mediators associated with insulin resistance. Peripheral
      insulin and glucose intolerance were improved in both MIC-1/GDF15-treated high
      fat-fed and chow-fed mice compared to that of their vehicle-treated control mice.
      CONCLUSIONS: MIC-1/GDF15 is highly effective in reducing adiposity and correcting
      the metabolic dysfunction of mice with high-fat fed. These studies suggest that
      MIC-1/GDF15 may be a candidate anti-obesity therapeutic.

PMID- 29026217
TI  - CTRP4: a new member of the adipocytokine family.

PMID- 29026216
TI  - Associations of maternal and cord blood adipokines with offspring adiposity in
      Project Viva: is there an interaction with child age?
AB  - OBJECTIVES: Higher leptin and lower adiponectin correlate with adult and
      childhood adiposity, but it is unclear how exposure to these adipokines during
      gestation relates to offspring growth. We aimed to investigate the relationships
      of maternal and cord adipokines with offspring adiposity across childhood to
      early adolescence, as well as interactions with child age. METHODS: In mother
      child pairs in the Project Viva cohort, we measured adipokines in mothers at
      second trimester (n=1106) and in cord blood at birth (n=657). We measured
      offspring adiposity indices at early childhood (mean 3.3+/-s.d. 0.3 years), mid
      childhood (7.9+/-0.8 years) and early adolescence (13.2+/-0.9 years). We analyzed
      associations of maternal and cord adipokines with offspring longitudinal
      adiposity using a linear mixed model adjusting for pre-pregnancy body mass index
      (BMI), gestational weight gain (GWG), and other confounders. RESULTS: Mothers
      with higher BMI and GWG had higher leptin. Offspring born to mothers with the
      highest vs lowest quartile of leptin had lower BMI z-score (-0.49 units, 95%
      confidence interval (CI):-0.72,-0.26), waist circumference (-2.6 cm, 95% CI: 
      3.7,-1.5) and sum of subscapular and triceps skinfolds (-2.8 mm, 95% CI: -4.1,
      1.4) in early life. An interaction term between maternal leptin and child age was
      positive, suggesting that the associations between maternal leptin and child
      adiposity were not constant over time. Offspring born to mothers with lowest vs
      highest quartile of maternal adiponectin had lower early life adiposity (BMI z
      score -0.27 units, 95% CI: -0.48,-0.05). Results were similar for cord leptin but
      not cord adiponectin. CONCLUSIONS: Our findings showed higher maternal and cord
      leptin, and lower maternal adiponectin are associated with lower offspring
      adiposity from childhood to early adolescence, independent of maternal BMI and
      GWG. However, the strength of these associations was not constant over time.

PMID- 29026218
TI  - IgD class switch recombination is not controlled through the immunoglobulin heavy
      chain 3' regulatory region super-enhancer.

PMID- 29026219
TI  - Regulation of B-1a cells: another novel function of the basic helix-loop-helix
      transcriptional regulator BHLHE41.

PMID- 29026220
TI  - Perspectives: 'Patients with 40-60/day habits are now few and far between'.

PMID- 29026221
TI  - Articaine: friend or foe?
AB  - Articaine and neurotoxicity - a review.

PMID- 29026225
TI  - Unsupported conclusions.

PMID- 29026224
TI  - Oral surgery II: Part 2. The maxillary sinus (antrum) and oral surgery.
AB  - The maxillary sinus is the largest of the four paranasal sinuses and, being
      anatomically adjacent to the dentate region of the maxilla, is commonly a source
      of problems - not simply in terms of conditions affecting the sinus but also in
      establishing an accurate diagnosis. As anyone who has suffered both sinusitis and
      a dental abscess in the posterior maxilla will tell you, the symptoms are almost
      indistinguishable. For this reason, a sound understanding of the maxillary sinus
      is an essential requisite for all dentists.

PMID- 29026229
TI  - Erratum: Quick release mechanism.
AB  - This corrects the article DOI: 10.1038/sj.bdj.2017.691.

PMID- 29026228
TI  - Focal infection revisited - the swinging of the pendulum.
AB  - A historical review, focusing not only on disease, but also on the relationship
      between the medical and dental professions.

PMID- 29026230
TI  - Dental radiography: Short roots.

PMID- 29026231
TI  - Oral surgery: The drug holiday.

PMID- 29026232
TI  - Changing the dental landscape.

PMID- 29026233
TI  - Trends in dental caries in children and adolescents according to poverty status
      in the United States from 1999 through 2004 and 2011 through 2014.
AB  - Study shows an improving trend in child dental health in the USA and indicates
      that targeted interventions may be successful.

PMID- 29026234
TI  - Compliance with the guide for commissioning oral surgery: an audit and
      discussion.
AB  - Introduction The Guide for commissioning oral surgery and oral medicine published
      by NHS England (2015) prescribes the level of complexity of oral surgery and oral
      medicine investigations and procedures to be carried out within NHS services.
      These are categorised as Level 1, Level 2, Level 3A and Level 3B. An audit was
      designed to ascertain the level of oral surgery procedures performed by
      clinicians of varying experience and qualification working in a large oral
      surgery department within a major teaching hospital.Materials and methods Two
      audit cycles were conducted on retrospective case notes and radiographic review
      of 100 patient records undergoing dental extractions within the Department of
      Oral Surgery at King's College Dental Hospital. The set gold standard was: '100%
      of Level 1 procedures should be performed by dental undergraduates or discharged
      back to the referring general dental practitioner'. Data were collected and
      analysed on a Microsoft Excel spreadsheet. The results of the first audit cycle
      were presented to all clinicians within the department in a formal meeting,
      recommendations were made and an action plan implemented prior to undertaking a
      second cycle.Results The first cycle revealed that 25% of Level 1 procedures met
      the set gold standard, with Level 2 practitioners performing the majority of
      Level 1 and Level 2 procedures. The second cycle showed a marked improvement,
      with 66% of Level 1 procedures meeting the set gold standard.Conclusion Our audit
      demonstrates that whilst we were able to achieve an improvement with the set gold
      standard, several barriers still remain to ensure that patients are treated by
      the appropriate level of clinician in a secondary care setting. We have used this
      audit as a foundation upon which to discuss the challenges faced in
      implementation of the commissioning framework within both primary and secondary
      dental care and strategies to overcome these challenges, which are likely to be
      encountered in any NHS care setting in which oral surgery procedures are
      performed.

PMID- 29026235
TI  - Health policy: Hospital cutbacks.

PMID- 29026237
TI  - Parental perception of oral health-related quality of life of Syrian refugee
      children.
AB  - A questionnaire- and interview-based study concerning access to dental care is
      limited in refugee camps.

PMID- 29026240
TI  - Alternative sugars: Honey.

PMID- 29026244
TI  - Oral health: Treating refugees.

PMID- 29026248
TI  - Spotting the signs.
AB  - The impact of bulimia nervosa on oral health: A review of the literature.

PMID- 29026250
TI  - Thousands of new oral health educators.
AB  - Oral health promotion in the community pharmacy: an evaluation of a pilot oral
      health promotion intervention.

PMID- 29026253
TI  - Paula Moynihan: 'We really need to look at a holistic, systemic approach'.

PMID- 29026255
TI  - Robert W McCarley-Pre-eminent Researcher, Mentor, and Friend.

PMID- 29026256
TI  - Jaak Panksepp: Pioneer of Affective Neuroscience.

PMID- 29026257
TI  - Fronto-Striatal Glutamate in Autism Spectrum Disorder and Obsessive Compulsive
      Disorder.
AB  - This corrects the article DOI: 10.1038/npp.2016.260.

PMID- 29026258
TI  - Comparison of High-Pressure Behavior of Physicochemical Properties of the Di- and
      Triacylglycerols Established by Ultrasonic Methods.
AB  - Two samples of triacylglycerols i.e., olive oil and triolein, and one sample of
      diacylglycerol were investigated. In the course of compression, the density of
      the samples was determined by measurements of the change of piston position in a
      pressure chamber and volume correction due to chamber expansion under pressure.
      The speed of sound was evaluated from the time of flight of an ultrasonic impulse
      between emitting and receiving transducers placed in the high pressure chamber.
      The adiabatic compressibility, the intermolecular free length, the molar volume,
      the van der Waals' constant b and the surface tension were evaluated from the
      density, the speed of sound and the average molecular mass. All tested liquids
      undergo a high-pressure phase transition. Discontinuities in the measured
      isotherms of the physicochemical parameters of the investigated oils indicate the
      presence of high-pressure phase transitions. Moreover the time dependent change
      of pressure at constant volume during the phase transition was measured. The
      fundamental difference in the molecular structure of these acylglycerols
      influences their behavior significantly under high pressure.

PMID- 29026259
TI  - Identification of a TBHQ-Interfering Peak in Crude Canola Oil Using AOCS Official
      Method Ce 6-86 and its Chromatographic Resolution.
AB  - AOCS Official Method Ce 6-86 "Antioxidants, Liquid Chromatographic Method" was
      originally developed to confirm the correct antioxidant was added at the
      specified concentration to refined oils. Today, this method is increasingly
      utilized to validate that antioxidants are absent from oil products. False
      positive results can have a significant impact on the ability to sell products in
      specific markets and can impart additional business expenditures for conclusive
      secondary analyses. In the current work, quantification of tert-butylhydroquinone
      (TBHQ) in crude canola/rapeseed oil using liquid chromatography (LC) with
      ultraviolet (UV) detection was compromised by an interfering peak. Analyses using
      liquid chromatography-mass spectrometry (GC-MS) and high-resolution accurate mass
      LC-MS identified the interferent as 2,6-dimethoxy-4-vinylphenol (canolol), an
      endogenous compound present in crude canola/rapeseed oil. Resolution of canolol
      and TBHQ using LC-UV can be achieved via minor modification of the
      chromatographic conditions.

PMID- 29026260
TI  - Leisure Noise and Hearing.

PMID- 29026262
TI  - Personal Listening Devices in Australia: Patterns of Use and Levels of Risk.
AB  - Personal listening devices (PLDs) have the potential to increase the risk of
      noise-induced hearing loss (NIHL) for users. The present study aimed to
      investigate the nature and extent of the risk posed, by describing the user
      profile of a PLD population, identifying listening habits of that population, and
      examining whether PLD risk status is associated with hearing damage. A sample of
      4,185 Australian PLD users completed an online survey about listening behaviors
      and hearing health. Listeners were characterized as low, high, or very high-risk
      based on daily noise dose estimates calculated from self-reported listening
      volume and durations. Listening patterns and hearing difficulties were examined
      in relation to risk status. Results indicated differences in listening volumes
      and durations with respect to age, with higher listening volumes reported for
      environments with greater background noise. Fifteen percent of participants'
      usage was classified as posing a potential risk to hearing, with a significantly
      greater proportion of younger people in higher-risk categories. Forty-one percent
      of participants reported feeling they have a hearing loss, with ~20% reporting
      difficulties with speech in noise. For 18- to 35-year-olds, higher-risk status
      was associated with a greater proportion of self-reported hearing difficulties,
      including perceived poorer speech perception. These results have implications for
      hearing health promotion activities and suggest that messages should focus on
      either volume levels or durations depending on the particular activity in which
      the PLD is used. In addition, the results underline the importance of placing PLD
      exposure in the context of individuals' wider noise exposure. Although PLD use
      alone is not placing the majority of users at risk, it may be increasing the
      likelihood that individuals' cumulative noise exposure will exceed safe levels.

PMID- 29026261
TI  - Prevention of Noise-Induced Hearing Loss from Recreational Firearms.
AB  - In the United States and other parts of the world, recreational firearm shooting
      is a popular sport that puts the hearing of the shooter at risk. Peak sound
      pressure levels (SPLs) from firearms range from ~140 to 175 dB. The majority of
      recreational firearms (excluding small-caliber 0.17 and 0.22 rifles and air
      rifles) generate between 150 and 165 dB peak SPLs. High-intensity impulse sounds
      will permanently damage delicate cochlear structures, and thus individuals who
      shoot firearms are at a higher risk of bilateral, high-frequency, noise-induced
      hearing loss (NIHL) than peer groups who do not shoot. In this article, we
      describe several factors that influence the risk of NIHL including the use of a
      muzzle brake, the number of shots fired, the distance between shooters, the
      shooting environment, the choice of ammunition, the use of a suppressor, and
      hearing protection fit and use. Prevention strategies that address these factors
      and recommendations for specialized hearing protectors designed for shooting
      sports are offered. Partnerships are needed between the hearing health community,
      shooting sport groups, and wildlife conservation organizations to develop and
      disseminate accurate information and promote organizational resources that
      support hearing loss prevention efforts.

PMID- 29026263
TI  - Effects of Recreational Noise on Threshold and Suprathreshold Measures of
      Auditory Function.
AB  - Noise exposure that causes a temporary threshold shift but no permanent threshold
      shift can cause degeneration of synaptic ribbons and afferent nerve fibers, with
      a corresponding reduction in wave I amplitude of the auditory brainstem response
      (ABR) in animals. This form of underlying damage, hypothesized to also occur in
      humans, has been termed synaptopathy , and it has been hypothesized that there
      will be a hidden hearing loss consisting of functional deficits at suprathreshold
      stimulus levels. This study assessed whether recreational noise exposure history
      was associated with smaller ABR wave I amplitude and poorer performance on
      suprathreshold auditory test measures. Noise exposure histories were collected
      from 26 men and 34 women with hearing thresholds <= 25 dB hearing loss (HL; 250
      Hz to 8 kHz), and a variety of functional suprathreshold hearing tests were
      performed. Wave I amplitudes of click-evoked ABR were obtained at 70, 80, 90, and
      99 dB (nHL) and tone-burst evoked ABR were obtained at 90 dB nHL. Speech
      recognition performance was measured in quiet and in competing noise, using the
      Words in Noise test, and the NU-6 word list in broadband noise (BBN). In
      addition, temporal summation to tonal stimuli was assessed in quiet and in
      competing BBN. To control for the effects of subclinical conventional hearing
      loss, distortion product otoacoustic emission amplitude, an indirect measure of
      outer hair cell integrity, was measured. There was no statistically significant
      relationship between noise exposure history scores and ABR wave I amplitude in
      either men or women for any of the ABR conditions. ABR wave I amplitude and noise
      exposure history were not reliably correlated with suprathreshold functional
      hearing tests. Taken together, this study found no evidence of noise-induced
      decreases in ABR wave I amplitude or signal processing in noise in a cohort of
      subjects with a history of recreational noise exposure.

PMID- 29026264
TI  - More to Lose? Noise-Risk Perceptions of Young Adults with Hearing Impairment.
AB  - This study investigated the attitudes and behaviors of young adults with hearing
      impairment (HI), in relation to leisure noise. It was hypothesized that young
      people with HI would have more negative perceptions of noise exposure than their
      peers with nonimpaired (normal) hearing (NH) and would engage more frequently in
      self-protective behaviors. Questionnaires were administered as part of a larger
      study of young Australians with: (1) preadult onset HI and (2) NH. Data from
      adults (age range 18 to 24 years; n  = 79 with HI, n  = 131 with NH) were
      selected for the current analysis. Attitudes data for HI and NH groups were
      compared using chi-square tests, and the reported use of hearing aids and
      personal hearing protectors (PHPs) in leisure environments was quantified. Most
      participants with HI and NH regarded leisure noise as a health hazard but rated
      their own noise-injury risk as lower than that of their peer group. The use of
      PHPs was low overall, and many participants with HI reported using hearing aids
      (switched on) during noisy leisure activities. An equal and substantial
      proportion of participants with HI and NH reported dislike and avoidance of loud
      activities. Systematic noise management in leisure environments would address
      noise-injury risk and also enhance social participation.

PMID- 29026265
TI  - Attitudes, Risk Behavior, and Noise Exposure among Young Adults with Hearing
      Problems: Identifying a Typology.
AB  - This study explored attitudes toward leisure noise, use of hearing protection,
      and perceived susceptibility to leisure-noise damage in young adults with hearing
      problems. Twelve participants aged between 18 and 35 years took part in a
      semistructured interview. Data were analyzed using framework analysis. The
      results showed that a positive attitude to noise, a passion for loud music, a
      lack of knowledge of the consequences of noise damage, and perceived low risk of
      hearing problems were associated with people not using earplugs. The aesthetics,
      comfort, perceived effects on music quality and attitude of others were all
      barriers to earplug use. Of those who had used earplugs, previous hearing-related
      symptoms and concern about future hearing damage were the main motivators for
      use. Four types of people were identified to describe the variation in attitudes
      and behaviors: those who had no change in behavior or concern about damage; those
      who were concerned and used earplugs; those who were concerned and avoided loud
      venues; and those who were concerned about communication difficulties only.
      Considering the wide variability, it may be more effective to shift attention
      from trying to change individual attitudes and behaviors to considering systemic
      changes to protect hearing, through ensuring the music industry and relevant
      authorities take greater responsibility.

PMID- 29026266
TI  - Understanding Why People Enjoy Loud Sound.
AB  - Sounds at levels that can injure the ear are regarded as enjoyable by many
      people. In many societies, a common form of this behavior is listening to loud
      music, either via personal audio systems or at music venues. Drawing on theory
      from the literature around loud sound and emotional responses to music, and
      combining it with concepts of physiological sound adaptation and classical
      conditioning, we developed a model of the process that may underlie people's
      enjoyment of loud sound, particularly loud music in nightclubs. The Conditioning,
      Adaptation, and Acculturation to Loud Music (CAALM) model proposes that the
      benefits associated with loud sound, alongside other desirable aspects of
      nightclubs, provide the unconditioned stimuli. Over time regular clubbers become
      conditioned to enjoy loud sound in itself. Exposure to loud sound also causes
      adaptation within the auditory system, so there is both a desire for, and
      tolerance of, loud sound during leisure time. This sets up an expectation of loud
      music as a cultural norm, and staff of leisure venues, who are themselves part of
      that culture, set music levels to meet customer expectations; and a cycle is
      perpetuated. This theory may be a useful consideration for health promotion and
      hearing conservation interventions.

PMID- 29026267
TI  - Control of reaction-diffusion equations on time-evolving manifolds.
AB  - Among the main actors of organism development there are morphogens, which are
      signaling molecules diffusing in the developing organism and acting on cells to
      produce local responses. Growth is thus determined by the distribution of such
      signal. Meanwhile, the diffusion of the signal is itself affected by the changes
      in shape and size of the organism. In other words, there is a complete coupling
      between the diffusion of the signal and the change of the shapes. In this paper,
      we introduce a mathematical model to investigate such coupling. The shape is
      given by a manifold, that varies in time as the result of a deformation given by
      a transport equation. The signal is represented by a density, diffusing on the
      manifold via a diffusion equation. We show the non-commutativity of the transport
      and diffusion evolution by introducing a new concept of Lie bracket between the
      diffusion and the transport operator. We also provide numerical simulations
      showing this phenomenon.

PMID- 29026268
TI  - Characteristic clinical features of adipsic hypernatremia patients with
      subfornical organ-targeting antibody.
AB  - Adipsic hypernatremia is a rare disease presenting as persistent hypernatremia
      with disturbance of thirst regulation and hypothalamic dysfunction. As a result
      of congenital disease, tumors, or inflammation, most cases are accompanied by
      structural abnormalities in the hypothalamic-pituitary area. While cases with no
      hypothalamic-pituitary structural lesion have been reported, their etiology has
      not been elucidated. Recently, we reported three patients with adipsic
      hypernatremia whose serum-derived immunoglobulin (Ig) specifically reacted with
      mouse subfornical organ (SFO) tissue. As one of the circumventricular organs
      (CVOs) that form a sensory interface between the blood and brain, the SFO is a
      critical site for generating physiological responses to dehydration and
      hypernatremia. Intravenous injection of the patient's Ig fraction induced
      hypernatremia in mice, along with inflammation and apoptosis in the SFO. These
      results support a new autoimmunity-related mechanism for inducing adipsic
      hypernatremia without demonstrable hypothalamic-pituitary structural lesions. In
      this review, we aim to highlight the characteristic clinical features of these
      patients, in addition to etiological mechanisms related to SFO function. These
      findings may be useful for diagnosing adipsic hypernatremia caused by an
      autoimmune response to the SFO, and support development of new strategies for
      prevention and treatment.

PMID- 29026270
TI  - Longitudinal study on the effectiveness of vitamin D supplements in exclusively
      breast-fed infants.
AB  - Vitamin D deficiency is a common health problem in infancy. Breast-fed infants
      are at a higher risk of rickets than formula-fed infants. We observed
      fluctuations in vitamin D levels in infancy (phase I, 2009-2010) and considered
      the benefits of vitamin D supplementation specifically in exclusively breast-fed
      infants in Japan (phase II, 2015). Infants born at our hospital were enrolled in
      this study. In phase I, we measured 25-hydroxyvitamin D [25(OH)D] levels at 1- to
      6-mo intervals from birth. In phase II, we measured 25(OH)D levels before and
      after supplementation. Vitamin D deficiency was defined as 25(OH)D levels of < 20
      ng/mL. All 38 infants in phase I were deficient at birth, and none of the
      exclusively breast-fed infants achieved 25(OH)D sufficiency by 5 mo of age.
      Formula-fed infants achieved 25(OH)D sufficiency earlier. The majority of the 71
      infants in phase II were deficient at birth. We recommended an oral vitamin D
      supplement at a daily dose of 4.0 ug for the 15 exclusively breast-fed infants,
      starting at 1 mo of age; 14 (93.3%) of them achieved 25(OH)D sufficiency by 5
      months of age. Exclusively breast-fed infants are at a high risk of vitamin D
      deficiency; adequate supplementation is an effective preventative strategy.

PMID- 29026269
TI  - Clinical characteristics of septo-optic dysplasia accompanied by congenital
      central hypothyroidism in Japan.
AB  - Septo-optic dysplasia (SOD) is a congenital anomaly in which agenesis of the
      septum pellucidum and optic nerve hypoplasia are accompanied by hypopituitarism.
      Typically, the symptoms develop in 3 organs, the brain, eyes, and pituitary, and
      approximately one third of the patients present with all of the three cardinal
      features. The diagnostic criteria for SOD were established in Japan in 2015. The
      purpose of this study is to review clinical features regarding SOD patients with
      hypopituitarism in Japan. In this study, 21 patients with SOD were identified by
      a questionnaire survey for congenital central hypothyroidism. All 3 symptoms of
      SOD, agenesis of the septum pellucidum, optic nerve hypoplasia, and endocrine
      abnormalities, were noted in 8 of the 21 patients. Various combinations of
      pituitary hormone deficiencies were observed in patients with SOD, although SOD
      is a rare, heterogeneous, and phenotypically variable disorder, some patients
      develop hypoglycemia and convulsions after birth, and early intervention with
      hormone replacement is necessary in severe cases. In addition, 14 cases were
      complicated by both developmental delay and epilepsy, and 16 cases involved eye
      abnormalities. Therefore, in addition to an early endocrinological diagnosis and
      hormone replacement, consultation with both pediatric neurologists and pediatric
      ophthalmologists is necessary.

PMID- 29026271
TI  - Acanthosis nigricans in a Japanese boy with hypochondroplasia due to a K650T
      mutation in FGFR3.
AB  - Acanthosis nigricans (AN) is observed in some cases of skeletal dysplasia.
      However, AN has occasionally been reported in patients with hypochondroplasia
      (HCH), and a clinical diagnosis is sometimes difficult when its physical and
      radiological features are mild. Mutations in the gene encoding the fibroblast
      growth factor receptor 3 (FGFR3) have been identified as the cause of some types
      of skeletal dysplasia, which is diagnostically useful. Here, we report the case
      of a 3-yr-old Japanese boy who presented with AN. His height, weight, head
      circumference, and arm span were 91.7 cm (-1.95 SD), 16.3 kg, 54.0 cm (+2.6 SD),
      and 88.0 cm, respectively. In addition to the AN, he also exhibited a mild height
      deficit and macrocephaly, which prompted a search for FGFR3 mutations, although
      no skeletal disproportion, exaggerated lumbar lordosis, or facial dysmorphism was
      observed, and only slight radiological abnormalities were noted. A definitive
      diagnosis of HCH was made based on FGFR3 gene analysis, which detected a
      heterozygous K650T mutation. Insulin insensitivity was not found to have
      contributed to the development of AN. In individuals with AN, careful assessments
      for symptoms of HCH are important, regardless of the presence or absence of a
      short stature, and FGFR3 gene analysis is recommended in such cases.

PMID- 29026273
TI  - Detection of early stage medullary thyroid carcinoma by measuring serum
      calcitonin using an electro chemiluminescence immuno-assay: A case report of a
      young Japanese woman with a high-risk RET mutation.
AB  - Medullary thyroid carcinoma (MTC) in multiple endocrine neoplasia type 2 (MEN2)
      is an autosomal dominant disorder caused by the mutation of the RET proto
      oncogene, that shows nearly complete penetration. The American Thyroid
      Association guidelines recommend prophylactic thyroidectomy for patients with
      high-risk RET mutations. However, in Japan, ethical and medical issues may
      preclude prophylactic treatment in young patients. Hence, an early diagnosis of
      MTC is necessary to ensure a favorable outcome. Here, we report the case of a
      young Japanese girl with a high-risk RET mutation, diagnosed with very early
      stage MTC using serum calcitonin (Ctn) values measured using an electro
      chemiluminescence immuno-assay (ECLIA). The Japanese girl with a family history
      of MEN2 had been followed at our hospital since she was 5-mo-old. RET analysis
      revealed that she displayed a Cys634Gly mutation. The patient underwent annual
      neck ultrasonography and calcium infusion testing. When she was 8-yr-old, the Ctn
      level, measured using ECLIA, dramatically increased with calcium stimulation,
      from a baseline of 11.3 pg/mL to 333 pg/mL. She subsequently underwent total
      thyroidectomy and was diagnosed with stage I MTC. Detecting early stage MTC by
      monitoring serum Ctn measured by ECLIA, may represent a useful strategy for
      patients with high-risk RET mutations.

PMID- 29026272
TI  - Incidence of diabetes mellitus and neoplasia in Japanese short-statured children
      treated with growth hormone in the Genetics and Neuroendocrinology of Short
      Stature International Study (GeNeSIS).
AB  - The primary goal of the Genetics and Neuroendocrinology of Short Stature
      International Study (GeNeSIS) was to assess the safety and effectiveness of
      Humatrope(r), a GH preparation, in the treatment of pediatric patients with short
      stature. We report our findings in the GH-treated Japanese pediatric population
      focusing on the incidence of type 2 diabetes (T2D) and occurrence of neoplasms. A
      total of 2,345 Japanese patients were assessed for safety. During a mean
      observation period of 3.2 yr, T2D occurred in 3 patients (0.13%) and slowly
      progressive insulin-dependent diabetes mellitus (SPIDDM) related to underlying
      mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
      (MELAS) in 1 patient (0.04%). Neoplasms were reported in 13 patients (0.56%),
      including 1 patient with brain tumor (germinoma) and 5 with craniopharyngiomas (4
      recurrences); the remainder were benign, typically dermatological, neoplasms. The
      incidence of diabetes mellitus determined in the study did not differ from
      previous reports in GH-treated pediatric patients, and there was no apparent
      increase in the risk of new neoplastic lesions or malignant tumors.

PMID- 29026274
TI  - A case of an infant with congenital combined pituitary hormone deficiency and
      normalized liver histology of infantile cholestasis after hormone replacement
      therapy.
AB  - Congenital combined pituitary hormone deficiency (CPHD) may present with
      cholestasis in the neonate or during early infancy. However, its precise
      mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and
      hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily
      improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct
      bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no
      signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation
      of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging
      (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic
      posterior lobe, and the patient was diagnosed with congenital CPHD based on
      decreased secretion of cortisol and GH by the pituitary anterior lobe load test.
      D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We
      subsequently began replacement with levothyroxine (L-T4) and GH, and liver
      histology showed normal interlobular bile ducts at 8 mo old. This is the first
      case report of proven histological improvement after hormone replacement therapy.
      This suggested that pituitary-mediated hormones, especially cortisol, might be
      involved in the development of the bile ducts.

PMID- 29026275
TI  - A case of 45,X/47,XXX mosaic Turner syndrome with limb length discrepancy.
AB  - Patients with Turner syndrome (TS) frequently show short stature and skeletal
      deformities, such as kyphosis and scoliosis. However, to the best of our
      knowledge, limb length discrepancy (LLD) has not yet been reported in patients
      with TS. The case of a 12-yr-old girl with 45,X/47,XXX mosaic TS showing LLD is
      herein presented. She was on GH therapy for short stature and was noted to have
      scoliosis in the standing position at a regular examination; however, the
      scoliosis became less evident in the supine position, which is indicative of LLD.
      The length of the left leg was 5.0 cm shorter than that of the right leg when
      measured. She was referred to orthopedics and underwent right distal femoral and
      right proximal tibial staple epiphysiodesis to shorten the abnormally long limb
      at 10 yr 6 mo of age. One year after the operation, the LLD decreased from 5.0 to
      1.5 cm. During this period, GH was continued. LLD is a rare complication in TS,
      but when patients with TS show scoliosis in the standing position, re-evaluation
      for scoliosis in the supine position should be performed and the lengths of both
      legs should be measured.

PMID- 29026276
TI  - Five cases of childhood-onset Graves' disease treated with either surgery or
      radio-iodine therapy.
AB  - There are three major therapeutic options for the treatment of Graves' disease
      (GD): antithyroid drugs (ATDs), thyroidectomy, and radio-iodine (RAI) therapy.
      ATDs are the initial treatment option for children. However, some pediatric GD
      patients who are initially treated with ATDs require other type of treatments
      later on. We reviewed the medical records of childhood-onset GD cases
      retrospectively to report the clinical course of patients who received either
      surgery or RAI therapy subsequent to treatment with ATDs. Childhood-onset GD was
      successfully managed in five girls with non-ATD treatments at the age of 7-14 yr
      following an unfavorable outcome of initial ATD treatment. Four cases had surgery
      and one case was managed with RAI therapy. The reasons for switching to non-ATD
      treatment included poor compliance, failure to maintain remission, serious
      adverse events resulting from ATDs, and religious background. In conclusion,
      surgery and RAI therapy could be good alternative treatment options for children
      with GD.

PMID- 29026277
TI  - Novel splice site mutation in GATA3 in a patient with HDR syndrome.

PMID- 29026278
TI  - A Japanese boy with fructose-1,6-bisphosphatase deficiency who had a novel FBP1
      mutation (p.Phe90Val).

PMID- 29026279
TI  - Inertial proximal alternating minimization for nonconvex and nonsmooth problems.
AB  - In this paper, we study the minimization problem of the type [Formula: see text],
      where f and g are both nonconvex nonsmooth functions, and R is a smooth function
      we can choose. We present a proximal alternating minimization algorithm with
      inertial effect. We obtain the convergence by constructing a key function H that
      guarantees a sufficient decrease property of the iterates. In fact, we prove that
      if H satisfies the Kurdyka-Lojasiewicz inequality, then every bounded sequence
      generated by the algorithm converges strongly to a critical point of L.

PMID- 29026280
TI  - M-test in linear models with negatively superadditive dependent errors.
AB  - This paper is concerned with the testing hypotheses of regression parameters in
      linear models in which errors are negatively superadditive dependent (NSD). A
      robust M-test base on M-criterion is proposed. The asymptotic distribution of the
      test statistic is obtained and the consistent estimates of the redundancy
      parameters involved in the asymptotic distribution are established. Finally, some
      Monte Carlo simulations are given to substantiate the stability of the parameter
      estimates and the power of the test, for various choices of M-methods,
      explanatory variables and different sample sizes.

PMID- 29026281
TI  - Quadratic convergence of monotone iterates for semilinear elliptic obstacle
      problems.
AB  - In this paper, we consider the numerical solution for the discretization of
      semilinear elliptic complementarity problems. A monotone algorithm is established
      based on the upper and lower solutions of the problem. It is proved that
      iterates, generated by the algorithm, are a pair of upper and lower solution
      iterates and converge monotonically from above and below, respectively, to the
      solution of the problem. Moreover, we investigate the convergence rate for the
      monotone algorithm and prove quadratic convergence of the algorithm. The monotone
      and quadratic convergence results are also extended to the discrete problems of
      the two-sided obstacle problems with a semilinear elliptic operator. We also
      present some simple numerical experiments.

PMID- 29026282
TI  - Hybrid Single-Port Cholecystectomy Vs Four-Port Cholecystectomy in Children.
AB  - BACKGROUND AND OBJECTIVES: Evidence is increasing that single-port or single
      incision laparoscopic cholecystectomy is a safe and feasible alternative for
      cholecystectomy in children. In this study, we sought to compare the single-port
      hybrid technique, which we originally reported in 2012, with the conventional 4
      port approach, in regards of complications, outcome, operative time and cost.
      METHODS: A retrospective, single-center comparison of hybrid single-port versus
      conventional 4-port laparoscopic cholecystectomy was performed in 98 consecutive
      pediatric patients between January 2010 and October 2014. Patient
      characteristics, intra- and postoperative outcomes, operative costs, and total
      hospitalization costs were compared between the 2 approaches using univariate and
      multivariate analyses. RESULTS: The single-port technique was utilized in 56
      (57%) pediatric patients who underwent laparoscopic cholecystectomy. The
      operative time for single-port procedures was shorter than that of the
      conventional technique (median, 85 minutes vs 114 minutes; P = .003). Patients
      with single-port procedures were less likely to have a cholangiogram compared to
      patients who underwent 4-port cholecystectomy. (9% vs 40%; P < .001). No
      statistically significant differences between the 2 cohorts were observed for
      intra- or postoperative outcomes. Although the 2 groups shared nearly the same
      median duration of hospitalization (22 hours vs 21 hours; P = .70), the single
      port group demonstrated a lower total cost of hospitalization (median cost, $7438
      vs $8783; P = .030) and lower operative cost (median, $3918 vs $4647; P < .001).
      CONCLUSION: Hybrid single-port laparoscopic cholecystectomy in children with
      uncomplicated gallbladder disease is feasible and equally safe, with similar
      intra- and postoperative outcomes compared with the conventional 4-port approach.
      It can contribute to global cost reduction because of lower operative and total
      hospitalization costs.

PMID- 29026283
TI  - Outcomes study between femtosecond laser-assisted cataract surgery and
      conventional phacoemulsification surgery using an active fluidics system.
AB  - PURPOSE: The purpose of this study was to compare intraoperative parameters
      between femtosecond laser-assisted cataract surgery (FLACS) and conventional
      phacoemulsification using Centurion(r) Vision System with Active Fluidics.
      SETTING: This study was performed at Brasilia Ophthalmologic Hospital, Brasilia,
      Federal District, Brazil. PATIENTS AND METHODS: This was a prospective randomized
      comparative study. Patients with the diagnosis of cataract and surgical
      extraction programmed were divided into two groups: conventional
      phacoemulsification and FLACS. Intraoperative data were collected and submitted
      for statistical analysis. RESULTS: A total of 400 eyes were enrolled, 200 in each
      group. There were no surgical complications. Groups were statistically equivalent
      in age and nucleus density. Cumulative dissipated energy and torsional time were
      significantly reduced in the FLACS group. Conventional surgery had less fluid
      usage, total case time and aspiration (ASP) time. CONCLUSION: FLACS with Active
      Fluidics System can reduce the ultrasound energy use during cataract surgery, in
      spite of increasing case time, fluid usage and ASP time.

PMID- 29026284
TI  - Anti-vascular endothelial growth factor therapy for the treatment of myopic
      choroidal neovascularization.
AB  - Myopic choroidal neovascularization (CNV) is a sight-threatening condition which
      occurs in eyes with myopia, particularly in those with pathologic myopia. It is
      the most common cause of CNV among patients younger than 50 years. Hemorrhage and
      exudation from the CNV lesion may eventually result in scarring or chorioretinal
      atrophy. While myopic CNV was previously treated with focal laser
      photocoagulation or photodynamic therapy (PDT), the current treatment of choice
      is anti-vascular endothelial growth factor (VEGF) agents. Many studies have
      demonstrated the efficacy of intravitreal anti-VEGF agents in the treatment of
      myopic CNV. The RADIANCE study reported that intravitreal ranibizumab was
      superior to PDT in eyes with myopic CNV (at 3 months, both groups receiving
      intravitreal ranibizumab gained 10.5 and 10.6 letters vs 2.2 letters among
      patients receiving PDT). In addition, the study demonstrated similar visual
      outcomes in eyes treated on the basis of visual acuity stabilization or disease
      activity criteria. Other clinical studies have provided evidence for the efficacy
      of ranibizumab and aflibercept in the treatment of myopic CNV. This review
      addresses the epidemiology, pathophysiology, and imaging characteristics of
      myopic CNV, and discusses the evidence for the efficacy of anti-VEGF agents as
      compared to laser photocoagulation and PDT.

PMID- 29026285
TI  - Efficacy of 0.05% epinastine and 0.1% olopatadine for allergic conjunctivitis as
      seasonal and preseasonal treatment.
AB  - PURPOSE: To evaluate the efficacy and safety of 0.05% epinastine and 0.1%
      olopatadine eye drop preparations as seasonal and preseasonal treatments in
      patients with seasonal allergic conjunctivitis (SAC). SUBJECTS AND METHODS: This
      was a prospective, randomized, case-control study involving two institutions. The
      subjects were patients diagnosed with SAC at two institutions between February
      and March in 2014. To examine the clinical effects of seasonal treatment, 0.05%
      epinastine and 0.1% olopatadine were administered, and their effects were
      investigated every 2 weeks (Stage 1). To evaluate the clinical effects of
      preseasonal therapy, in January 2015, the same eye drop preparations as adopted
      in Stage 1 were administered to patients who had participated in Stage 1 and
      provided consent to participate in this study, and their effects were
      investigated every month (Stage 2). RESULTS: In Stage 1, the 0.05% epinastine
      group consisted of 43 patients, and the 0.1% olopatadine group consisted of 42
      patients. There were significant improvements in the total symptom and objective
      finding scores at each time point after administration in comparison with those
      before its baseline, but there were no significant differences between the two
      groups. In Stage 2, the 0.05% epinastine group consisted of 15 patients, and the
      0.1% olopatadine group consisted of 14 patients. The rate of change in the total
      symptom score in comparison with that at the baseline of preseasonal treatment
      was significantly higher in the 0.1% olopatadine group 1 month after the start of
      treatment, suggesting symptom deterioration (P=0.025). There was no significant
      difference in the rate of change in the total objective finding score between the
      two groups. CONCLUSION: Seasonal treatment with 0.05% epinastine or 0.1%
      olopatadine was equally effective for patients with allergic conjunctivitis.
      However, for preseasonal therapy, 0.05% epinastine was more effective than 0.1%
      olopatadine.

PMID- 29026286
TI  - Intraoperative optical coherence tomography and ab interno trabecular meshwork
      surgery with the Trabectome.
AB  - IMPORTANCE: This study is the first description of the use of the intraoperative
      optical coherence tomography (iOCT) for trabecular meshwork surgery with the
      Trabectome in a regular clinical setting. BACKGROUND: The aim of this study is to
      evaluate intraoperatively the immediate success of ab interno trabeculotomy with
      the Trabectome defined as a removal of the trabecular meshwork. DESIGN: This is a
      retrospective clinical study performed in the University Eye Hospital, Medical
      School Hannover. PARTICIPANTS: A total of nine consecutive Caucasian patients
      suffering from primary open angle glaucoma, pigment dispersion glaucoma, or
      pseudoexfoliation glaucoma took part in the study. METHODS: All patients
      underwent ab interno trabeculotomy surgery with the Trabectome using a
      commercially available iOCT to visualize the anterior chamber angle (ACA) before
      and after the procedure. The visualization was done using a modified Swan-Jacobs
      lens (all nine patients) or without lens (view from above, five patients). MAIN
      OUTCOME MEASURES: The main outcome of this study is the success of visualization
      of the ACA on iOCT, especially the postprocedural visualization of the wound gap
      after removal of the trabecular meshwork. RESULTS: Using the view from above, the
      ACA could be visualized before and after the procedure in only two of the five
      cases. Using the modified Swan-Jacobs lens, the ACA could be visualized before
      the procedure and the trabecular meshwork opening after the procedure in all nine
      patients. CONCLUSION: The iOCT can be used to objectify the immediate success of
      the surgical procedure, ie, the removal of the trabecular meshwork, of ab interno
      trabeculotomy with the Trabectome. The procedure itself cannot be captured
      sufficiently via iOCT.

PMID- 29026287
TI  - Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions
      administered once or twice daily in rabbits, and clinical dosing implications.
AB  - PURPOSE: Fixed-combination medications can benefit patients requiring multiple
      agents to lower their intraocular pressure (IOP), but combining agents with
      complementary mechanisms of action is challenging if their dosing frequency
      differs. This study compares in vivo pharmacokinetic and ocular tolerability of
      bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of
      twice-daily dosing in glaucoma patients are also reviewed. METHODS: New Zealand
      White rabbits were administered bimatoprost 0.01% monotherapy or fixed
      combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes
      for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography
      tandem mass spectrometry. The pharmacokinetic parameters calculated included
      maximum observed concentration, time to maximum concentration, and area under the
      concentration-time curve. RESULTS: Due to extensive metabolism, bimatoprost
      concentration was below the quantitation limit by 1 hour post-dose in all
      samples. Bimatoprost acid exposure, however, could be measured up to 6-8 hours
      post-dose and was similar in the aqueous humor and iris-ciliary body
      (pharmacological site of action) of animals treated once or twice daily with
      either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%.
      Increasing dosage frequency in rabbits did not raise the incidence of drug
      related conjunctival hyperemia (most common adverse event associated with
      bimatoprost use in humans), suggesting comparable ocular tolerability of the once
      and twice-daily regimens for each formulation. CONCLUSION: Bimatoprost 0.01%
      administered once or twice daily as monotherapy and in fixed-combination with
      brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost
      acid, especially in the iris-ciliary body. Key findings from previous clinical
      studies suggest that by varying the concentration of benzalkonium chloride (a
      preservative with corneal penetration-enhancing properties), formulations of
      bimatoprost 0.01% can be administered once or twice daily. These findings support
      development of bimatoprost 0.01%-based fixed-dose combination therapies
      administered twice daily for patients who require multiple adjunctive medications
      to control their IOP.

PMID- 29026288
TI  - Assessment of quality of life, satisfaction with anticoagulation therapy, and
      adherence to treatment in patients receiving long-course vitamin K antagonists or
      direct oral anticoagulants for venous thromboembolism.
AB  - INTRODUCTION: Direct oral anticoagulants (DOACs) have shown non-inferiority and
      ease of use compared to vitamin K antagonists (VKA) in the treatment of venous
      thromboembolism (VTE). No study so far has been directed toward real-life
      experience of outpatients receiving anticoagulants for VTE in France. METHODS:
      This is an observational descriptive real-life epidemiological study, using three
      validated questionnaires (Morisky Medication Adherence Scale-8, EQ-5D, and part 2
      of the Perception of Anticoagulant Treatment Questionnaire), to assess adherence,
      quality of life, and satisfaction in 100 VTE outpatients receiving
      anticoagulation therapy by VKA (primary or switched from DOAC to VKA) or by DOAC
      (primary or switched from VKA to DOAC). RESULTS: Patients were very much
      satisfied with their treatment in both DOAC and VKA groups. Despite advantages of
      DOACs, therapeutic adherence was only moderate. The best adherence scores were
      observed in the primary VKA switched to DOAC for at least 3 months (S-DOAC)
      subgroup. Quality of life was better in the DOAC group mainly because of the
      absence of the requirement for blood testing. Most of the complaints concerned
      the pain/discomfort dimension in the VKA group and anxiety/depression dimension
      in the DOAC group. CONCLUSION: Patients were satisfied with their anticoagulant
      treatment, especially when they were involved in choosing the anticoagulant, and
      the treatment suited them. Quality of life of patients in the DOAC group was
      better than in the VKA group, but adherence remains to be improved. This study
      highlights the importance of the physician-patient relationship, pretreatment
      initiation, and follow-up of any anticoagulation therapy throughout.

PMID- 29026289
TI  - Can we predict postoperative complications in elderly Chinese patients with hip
      fractures using the surgical risk calculator?
AB  - PURPOSE: Hip fractures are associated with poor prognosis in elderly patients
      partly due to the high rate of postoperative complications. This study was aimed
      to investigate whether the surgical risk calculator is suitable for predicting
      postoperative complications in elderly Chinese patients with hip fractures.
      METHODS: The incidence of postoperative complications among 410 elderly patients
      with hip fractures was predicted by the surgical risk calculator and then
      compared with the actual value. The risk calculator model was evaluated using the
      following three metrics: Hosmer-Lemeshow test for the goodness-of-fit of the
      model, receiver operating characteristic curve (ROC) (also referred as C
      statistic) for the predictive specificity and sensitivity, and the Brier's score
      test for predictive accuracy. RESULTS: Preoperative risk factors including
      gender, age, preoperative functional status, American Society of
      Anesthesiologists grade, hypertension, dyspnea, dialysis, previous cardio
      vascular history, and cerebrovascular disease were positively correlated with the
      incidence of postoperative complications in elderly patients with hip fractures.
      The predicted complication incidence rate was well matched with the actual
      complication rate by Hosmer-Lemeshow test. The model had high sensitivity and
      specificity for predicting the mortality rate of these patients with a C
      statistic index of 0.931 (95% CI [0.883, 0.980]). The surgical calculator model
      had an accuracy of 90% for predicting the reoperation rate (Brier's score <0.01).
      CONCLUSIONS: The surgical risk calculator could be useful for predicting
      mortality and reoperation in elderly patients with hip fracture. Patients and
      surgeons may use this simple calculator to better manage the preoperative risks.

PMID- 29026290
TI  - Mindfulness training for psychological stress in family caregivers of persons
      with dementia: a systematic review and meta-analysis of randomized controlled
      trials.
AB  - Caring for a relative with dementia is extremely challenging; conventional
      interventions may not be highly effective or easily available on some occasions.
      This study aimed to explore the efficacy of mindfulness training in improving
      stress-related outcomes in family caregivers of people with dementia using a meta
      analytic review. We searched randomized controlled trials (RCT) through April
      2017 from five electronic databases, and assessed the risk of bias using the
      Cochrane Collaboration tool. Seven RCTs were included in our review. Mindfulness
      interventions showed significant effects of improvement in depression
      (standardized mean difference: -0.58, [95% CI: -0.79 to -0.37]), perceived stress
      (-0.33, [-0.57 to -0.10]), and mental health-related quality of life (0.38 [0.14
      to 0.63]) at 8 weeks post-treatment. Pooled evidence did not show a significant
      advantage of mindfulness training compared with control conditions in the
      alleviation of caregiver burden or anxiety. Future large-scale and rigorously
      designed trials are needed to confirm our findings. Clinicians may consider the
      mindfulness program as a promising alternative to conventional interventions.

PMID- 29026291
TI  - Psychometric properties of the Farsi version of Attitudes to Aging Questionnaire
      in Iranian older adults.
AB  - BACKGROUND: Attitudes to the aging process are affected by the individual's
      sociocultural background. The measurement of this important concept among older
      people in various societies requires the use of tools that are able to
      demonstrate both reliability and validity. OBJECTIVE: The objectives of this
      study were to translate and validate the Attitudes to Aging Questionnaire (AAQ)
      and investigate its psychometric features among Iranian older people. METHODS: In
      this methodological study, the Farsi version of the AAQ was validated among 400
      Iranian older adults who were members of citizen clubs in an urban area of Iran.
      Content, face and construct (exploratory factor analysis) validities of the AAQ
      were assessed. In addition, its reliability was assessed in terms of internal
      consistency and stability. For discriminant validity, the discriminant power of
      the AAQ in terms of gender and education levels was evaluated. Criterion validity
      showed a significant correlation between the most subscales of the AAQ and the
      Short Form 36 (SF-36) and World Health Organization Quality of Life (WHOQOL)
      questionnaires. Descriptive and inferential statistics were used for data
      analysis. RESULTS: The exploratory factor analysis confirmed the construct
      validity of the AAQ. The result of the test-retest reliability with a 2-week
      interval was satisfactory and reported as r=0.90 (p<0.001). The Cronbach's alpha
      coefficient was reported as 0.75 for the whole instrument and 0.85-0.93 for its
      dimensions. There were associations between the AAQ subscales, SF-36 quality of
      life (r=0.56, p<0.001) and WHOQOL-BREF (r=0.78, p<0.001), indicating an
      appropriate convergent validity. The ability to discriminate between male and
      female participants and those with lower and higher education levels was
      demonstrated, thus lending support to claims for adequate known-group validity.
      CONCLUSION: The Farsi version of the AAQ showed favorable validity and
      reliability. Therefore, it can be used for assessing attitudes toward aging among
      older adults.

PMID- 29026292
TI  - The effects of holistic health group interventions on improving the cognitive
      ability of persons with mild cognitive impairment: a randomized controlled trial.
AB  - PURPOSE: Persons with mild cognitive impairment (PwMCI) are at a higher risk of
      developing dementia than those without cognitive impairment. This research study
      aims to evaluate the effectiveness of a holistic health group intervention, which
      is based on the holistic brain health approach as well as an Eastern approach to
      health care, on improving the cognitive ability of Chinese PwMCI. RESEARCH
      METHODS: In a randomized controlled trial (RCT), 38 Chinese PwMCI were randomly
      assigned to either a 10-session holistic health intervention group or the control
      group. The holistic health treatment group attempted to promote the acceptance of
      their illness, enhance memory and coping skills, develop a positive lifestyle,
      maintain positive emotions, and facilitate emotional support among participants.
      The 10-session holistic health group intervention was structured, with each
      session conducted once per week and ~90 minutes in length. Control group patients
      and their family caregivers received standardized basic educational materials
      that provided basic information on cognitive decline for them to read at home.
      The Montreal Cognitive Assessment (MoCA) test was used to assess the cognitive
      ability of PwMCI in the pre- and posttreatment periods by a research assistant
      who was blind to the group assignment of the participants. RESULTS: The paired
      samples t-test indicated that the treatment group (n=18) showed significant
      improvement in the MoCA score, whereas the control group (n=20) did not.
      Moreover, 2*2 (group * time) repeated-measures analysis of covariance (ANCOVA)
      demonstrated that the holistic health group treatment was significantly more
      effective than the control intervention in improving the MoCA score, with a
      moderate effect size, and improving the delayed recall (ie, short-term memory),
      with a strong effect size, after controlling for age, sex, education, and marital
      status. CONCLUSION: This present RCT provides evidence to support the feasibility
      and effectiveness of the holistic health group intervention in improving the
      cognitive and short-term memory abilities of PwMCI.

PMID- 29026294
TI  - Comparison of the peripheral blood eosinophil count using near-patient testing
      and standard automated laboratory measurement in healthy, asthmatic and COPD
      subjects.
AB  - Near-patient testing (NPT) allows clinical decisions to be made in a rapid and
      convenient manner and is often cost effective. In COPD the peripheral blood
      eosinophil count has been demonstrated to have utility in providing prognostic
      information and predicting response to treatment during an acute exacerbation.
      For this potential to be achieved having a reliable NPT of blood eosinophil count
      would be extremely useful. Therefore, we investigated the use of the HemoCue(r)
      WBC Diff System and evaluated its sensitivity and specificity in healthy,
      asthmatic and COPD subjects. This method requires a simple skin prick of blood
      and was compared to standard venepuncture laboratory analysis. The HemoCue(r) WBC
      Diff System measured the peripheral blood eosinophil count in healthy, asthma and
      COPD subjects with very close correlation to the eosinophil count as measured by
      standard venepuncture. The correlations were unaffected by disease status. This
      method for the measurement of the peripheral blood eosinophil count has the
      potential to provide rapid near-patient results and thus influence the speed of
      management decisions in the treatment of airway diseases.

PMID- 29026293
TI  - Assessing capacity to consent for research in cognitively impaired older
      patients.
AB  - BACKGROUND: The number of clinical trials including older patients, and
      particularly patients with cognitive impairment, is increasing. While statutory
      provisions exist to make sure that the capacity to consent is assessed
      systematically for each patient, many gray areas remain with regard to how this
      assessment is made or should be made in the routine practice of clinical
      research. OBJECTIVES: The aim of this review was to draw up an inventory of
      assessment tools evaluating older patients' capacity to consent specifically
      applicable to clinical research, which could be used in routine practice.
      METHODS: Two authors independently searched PubMed, Cochrane, and Google Scholar
      data-bases between November 2015 and January 2016. The search was actualized in
      April 2017. We used keywords (MeSH terms and text words) referring to informed
      consent, capacity to consent, consent for research, research ethics, cognitive
      impairment, vulnerable older patients, and assessment tools. Existing reviews
      were also considered. RESULTS: Among the numerous existing tools for assessing
      capacity to consent, 14 seemed potentially suited for clinical research and six
      were evaluated in older patients. The MacArthur Competence Assessment Tool for
      Clinical Research (MacCAT-CR) was the most frequently cited. CONCLUSION: The
      MacCAT-CR is currently the most used and the best validated questionnaire.
      However, it appears difficult to use and time-consuming. A more recent tool, the
      University of California Brief Assessment of Capacity to Consent (UBACC), seems
      interesting for routine practice because of its simplicity, relevance, and
      applicability in older patients.

PMID- 29026295
TI  - Systemic effects of chronic obstructive pulmonary disease in young-old adults'
      life-space mobility.
AB  - PURPOSE: The objective was to assess whether dyspnea, peripheral muscle strength
      and the level of physical activity are correlated with life-space mobility of
      older adults with COPD. PATIENTS AND METHODS: Sixty patients over 60 years of age
      (40 in the COPD group and 20 in the control group) were included. All patients
      were evaluated for lung function (spirometry), life-space mobility (University of
      Alabama at Birmingham Study of Aging Life-Space Assessment), dyspnea severity
      (Modified Dyspnea Index), peripheral muscle strength (handgrip dynamometer),
      level of physical activity and number of daily steps (accelerometry). Groups were
      compared using unpaired t-test. Pearson's correlation was used to test the
      association between variables. RESULTS: Life-space mobility (60.41+/-16.93 vs
      71.07+/-16.28 points), dyspnea (8 [7-9] vs 11 [10-11] points), peripheral muscle
      strength (75.16+/-14.89 vs 75.50+/-15.13 mmHg), number of daily steps (4,865.4+/
      2,193.3 vs 6,146.8+/-2,376.4 steps), and time spent in moderate to vigorous
      activity (197.27+/-146.47 vs 280.05+/-168.95 minutes) were lower among COPD group
      compared to control group (p<0.05). The difference was associated with the lower
      mobility of COPD group in the neighborhood. CONCLUSION: Life-space mobility is
      decreased in young-old adults with COPD, especially at the neighborhood level.
      This impairment is associated to higher dyspnea, peripheral muscle weakness and
      the reduced level of physical activity.

PMID- 29026296
TI  - Trends in health care resource utilization and pharmacological management of COPD
      in Taiwan from 2004 to 2010.
AB  - RATIONALE: COPD has attracted widespread attention worldwide. The prevalence of
      COPD in Taiwan has been reported, but little is known about trends in health care
      resource utilization and pharmacologic management in COPD treatment. OBJECTIVE:
      The objective of this article was to study trends in health care resource
      utilization, pharmacologic management, and medical costs of COPD treatment in
      Taiwan. MATERIALS AND METHODS: Reimbursement claims in the Taiwan National Health
      Insurance System from 2004 to 2010 were collected. The disease burden of COPD,
      including health care resource utilization and medical costs, was evaluated.
      RESULTS: The pharmacy cost of COPD increased from 2004 to 2010 due to the
      increased utilization of long-acting muscarinic antagonist (LAMA) and fixed-dose
      combination of long-acting beta2-agonist and inhaled corticosteroid (LABA/ICS),
      whereas the cost of all other COPD-related medications decreased. The average
      outpatient department (OPD) cost per patient increased 29.3% from 1,070 USD in
      2004 to 1,383 USD in 2010. The highest average total medical cost per patient was
      3,434 USD in 2005, and it decreased 12.4% to 3,008 USD in 2010. There was no
      significant difference in the average number of OPD visits and emergency
      department visits per patient. The highest average number of hospital admissions
      was 0.81 in 2005, and it decreased to 0.65 in 2010. The average number of
      intensive care unit (ICU) admissions decreased from 0.52 in 2005 to 0.31 in 2010.
      CONCLUSION: From 2004 to 2010, the average total medical cost per patient of COPD
      was slightly decreased because of the decreased average number of hospital
      admissions and ICU admissions. The costs of both LAMA and LABA/ICS increased,
      while the cost for all other COPD-related medications decreased. These findings
      suggest that the increased utilization of LAMA and LABA/ICS may have contributed
      to the decreased average number of hospital admissions and ICU admissions in COPD
      patients from 2004 to 2010.

PMID- 29026297
TI  - In vitro study on anti-inflammatory effects of epigallocatechin-3-gallate-loaded
      nano- and microscale particles.
AB  - PURPOSE: This study aimed to develop an anti-inflammation system consisting of
      epigallo-catechin-3-gallate (EGCG) encapsulated in poly(lactide-co-glycolic acid)
      (PLGA) particles to promote wound healing. METHODS: Nano- and microscale PLGA
      particles were fabricated using a water/oil/water emulsion solvent evaporation
      method. The optimal particle size was determined based on drug delivery
      efficiency and biocompatibility. The particles were loaded with EGCG. The anti
      inflammatory effects of the particles were evaluated in an in vitro cell-based
      inflammation model. RESULTS: Nano- and microscale PLGA particles were produced.
      The microscale particles showed better biocompatibility than the nanoscale
      particles. In addition, the microscale particles released ~60% of the loaded
      drug, while the nanoscale particles released ~50%, within 48 hours. Thus,
      microscale particles were selected as the carriers. The optimal EGCG working
      concentration was determined based on the effects on cell viability and
      inflammation. A high EGCG dose (100 MUM) resulted in poor cell viability;
      therefore, a lower dose (<=50 MUM) was used. Moreover, 50 MUM EGCG had a greater
      anti-inflammatory effect than 10 MUM concentration on lipopolysaccharide-induced
      inflammation. Therefore, 50 MUM EGCG was selected as the working dose. EGCG
      loaded microparticles inhibited inflammation in human dermal fibroblasts.
      Interestingly, the inhibitory effects persisted after replacement of the drug
      loaded particle suspension solution with fresh medium. CONCLUSION: The EGCG
      loaded microscale particles are biocompatible and exert a sustained anti
      inflammatory effect.

PMID- 29026298
TI  - Therapeutic effects of lornoxicam-loaded nanomicellar formula in experimental
      models of rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease treated
      by nonsteroidal anti-inflammatory drugs (NSAIDs) including lornoxicam (LX).
      Nanocarriers have been used to increase the efficacy and reduce the side effects
      of various drugs. The objective of the present study was to compare the
      therapeutic efficacy of systemic administration of lornoxicam-loaded nanomicellar
      formula (LX-NM) with that of free LX. MATERIALS AND METHODS: The LX-loaded mixed
      polymeric nanomicellar formula was prepared by direct equilibrium technique. Two
      rat models were used in the study: carrageenan-induced acute edema and Freund's
      complete adjuvant (FCA)-induced chronic arthritis. RESULTS: The inhibitory effect
      of LX-NM on carrageenan-induced edema was higher than free LX for the same dose
      (1.3 mg/kg, i.p.). LX-NM (0.325 mg/kg, i.p.) produced effects comparable to that
      of diclofenac, which served as a standard. In the FCA model, daily treatment with
      LX-NM (0.325 mg/kg, i.p.) starting on day 14 significantly reduced the percentage
      of edema and increased weight growth. However, the same dose of LX failed to
      confer any significant change. Additionally, LX-NM significantly attenuated the
      rise of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, prostaglandin
      E2, nuclear factor-kappabeta, malondialdehyde and nitric oxide serum levels. In
      contrast, LX failed to show any significant reduction in elevated serum
      biomarkers except for TNF-alpha. CONCLUSION: LX-NM is an alternative delivery
      system that is simply prepared at low costs. It showed a superior therapeutic
      efficacy against RA compared to free LX. Thus, LX-NM can be considered as a
      promising candidate for treatment of RA and similar inflammatory disorders.

PMID- 29026299
TI  - Glycogen-gold nanohybrid escalates the potency of silymarin.
AB  - In this study, a glycogen-gold nanohybrid was fabricated to enhance the potency
      of a promising hepatoprotective agent silymarin (Sly) by improving its solubility
      and gut permeation. By utilizing a facile green chemistry approach, biogenic gold
      nanoparticles were synthesized from Annona reticulata leaf phytoconstituents in
      combination with Sly (SGNPs). Further, the SGNPs were aggregated in glycogen
      biopolymer to yield the therapeutic nanohybrids (GSGNPs). Transmission electron
      microscopy, UV-Vis spectroscopy, X-ray diffraction, and Fourier transform
      infrared spectroscopy analysis confirmed the successful formation and conjugation
      of both SGNPs and GSGNPs. The fabricated nanohybrids showed significant
      protection against CCl4-induced hepatic injury in Wistar rats and maintained
      natural antioxidant (superoxide dismutase and catalase) levels. Animals treated
      with GSGNPs (10 mg/kg) and SGNPs (20 mg/kg) retained usual hepatic functions with
      routine levels of hepatobiliary enzymes (aspartate transferase, alanine
      transaminase, alkaline phosphatase, and lactate dehydrogenase) and inflammatory
      markers (interleukin-1beta and tumor necrosis factor-alpha) with minimal lipid
      peroxidation, whereas those treated with 100 mg/kg of Sly showed the similar
      effect. These results were also supported by histopathology of the livers where
      pronounced hepatoprotection with normal hepatic physiology and negligible
      inflammatory infiltrate were observed. Significant higher plasma Cmax supported
      the enhanced bioavailability of Sly upon GSGNPs treatment compared to SGNPs and
      free Sly. Graphite furnace atomic absorption spectrophotometry analysis also
      substantiated the efficient delivery of GSGNPs over SGNPs. The fabricated
      therapeutic nanohybrids were also found to be biocompatible toward human
      erythrocytes and L929 mouse fibroblast cells. Overall, due to increased
      solubility, bioavailability and profuse gut absorption; GSGNPs demonstrated
      tenfold enhanced potency compared to free Sly.

PMID- 29026300
TI  - Noncovalent interaction-assisted drug delivery system with highly efficient
      uptake and release of paclitaxel for anticancer therapy.
AB  - An effective drug delivery system requires efficient drug uptake and release
      inside cancer cells. Here, we report a novel drug delivery system, in which
      paclitaxel (PTX) interacts with a novel cell penetrating peptide (CPP) through
      noncovalent interaction designed based on molecular simulations. This CPP/PTX
      complex confers high efficiency in delivering PTX into cancer cells not by
      endocytosis but by an energy-independent pathway. Once inside cells, the
      noncovalent interaction between PTX and the CPP may allow fast release of PTX
      within cells due to the direct translocation of CPP/PTX. This drug delivery
      system exhibits strong capacity for inhibition of tumor growth and offers a new
      avenue for the development of advanced drug delivery systems for anticancer
      therapy.

PMID- 29026301
TI  - Rational design of novel, fluorescent, tagged glutamic acid dendrimers with
      different terminal groups and in silico analysis of their properties.
AB  - Dendrimers are hyperbranched polymers with a multifunctional architecture that
      can be tailored for the use in various biomedical applications. Peptide
      dendrimers are particularly relevant for drug delivery applications due to their
      versatility and safety profile. The overall lack of knowledge of their three
      dimensional structure, conformational behavior and structure-activity
      relationship has slowed down their development. Fluorophores are often conjugated
      to dendrimers to study their interaction with biomolecules and provide
      information about their mechanism of action at the molecular level. However,
      these probes can change dendrimer surface properties and have a direct impact on
      their interactions with biomolecules and with lipid membranes. In this study, we
      have used computer-aided molecular design and molecular dynamics simulations to
      identify optimal topology of a poly(l-glutamic acid) (PG) backbone dendrimer that
      allows incorporation of fluorophores in the core with minimal availability for
      undesired interactions. Extensive all-atom molecular dynamic simulations with the
      CHARMM force field were carried out for different generations of PG dendrimers
      with the core modified with a fluorophore (nitrobenzoxadiazole and Oregon Green
      488) and various surface groups (glutamic acid, lysine and tryptophan). Analysis
      of structural and topological features of all designed dendrimers provided
      information about their size, shape, internal distribution and dynamic behavior.
      We have found that four generations of a PG dendrimer are needed to ensure
      minimal exposure of a core-conjugated fluorophore to external environment and
      absence of undesired interactions regardless of the surface terminal groups. Our
      findings suggest that NBD-PG-G4 can provide a suitable scaffold to be used for
      biophysical studies of surface-modified dendrimers to provide a deeper
      understanding of their intermolecular interactions, mechanisms of action and
      trafficking in a biological system.

PMID- 29026302
TI  - Ultrasmall AGuIX theranostic nanoparticles for vascular-targeted interstitial
      photodynamic therapy of glioblastoma.
AB  - Despite combined treatments, glioblastoma outcome remains poor with frequent
      local recurrences, indicating that a more efficient and local therapy is needed.
      In this way, vascular-targeted photodynamic therapy (VTP) could help tumor
      eradication by destroying its neovessels. In this study, we designed a
      polysiloxane-based nanoparticle (NP) combining a magnetic resonance imaging (MRI)
      contrast agent, a photosensitizer (PS) and a new ligand peptide motif (KDKPPR)
      targeting neuropilin-1 (NRP-1), a receptor overexpressed by angiogenic
      endothelial cells of the tumor vasculature. This structure achieves the detection
      of the tumor tissue and its proliferating part by MRI analysis, followed by its
      treatment by VTP. The photophysical properties of the PS and the peptide affinity
      for NRP-1 recombinant protein were preserved after the functionalization of NPs.
      Cellular uptake of NPs by human umbilical vein endothelial cells (HUVEC) was
      increased twice compared to NPs without the KDKPPR peptide moiety or conjugated
      with a scramble peptide. NPs induced no cytotoxicity without light exposure but
      conferred a photocytotoxic effect to cells after photodynamic therapy (PDT). The
      in vivo selectivity, evaluated using a skinfold chamber model in mice, confirms
      that the functionalized NPs with KDKPPR peptide moiety were localized in the
      tumor vessel wall.

PMID- 29026303
TI  - Delivery of antagomiR204-conjugated gold nanoparticles from PLGA sheets and its
      implication in promoting osseointegration of titanium implant in type 2 diabetes
      mellitus.
AB  - Impaired osseointegration of the implant remains the big hurdle for dental
      implant therapy in diabetic patients. In this study, the authors first identified
      that miR204 was strikingly highly expressed in the bone mesenchymal stem cells
      (BMSCs) of diabetic rats. Forced expression of miR204 repressed the osteogenic
      potential of BMSCs, while inhibition of miR204 significantly increased the
      osteogenic capacity. Moreover, the miR204 inhibitor was conjugated with gold
      nanoparticles (AuNP-antagomiR204) and dispersed them in the poly(lactic-co
      glycolic acid) (PLGA) solution. The AuNP-antagomiR204 containing PLGA solution
      was applied for coating the surface of titanium implant. Electron microscope
      revealed that an ultrathin sheet was formed on the surface of the implant, and
      the AuNPs were evenly dispersed in the coated PLGA sheet. Cellular experiments
      revealed that these encapsulated AuNP-antagomiR204 were able to be released from
      the PLGA sheet and uptaken by adherent BMSCs. In vivo animal study further
      confirmed that the AuNP-antagomiR204 released from PLGA sheet promoted
      osseointegration, as revealed by microcomputerized tomography (microCT)
      reconstruction and histological assay. Taken together, this study established
      that miR204 misexpression accounted for the deficient osseointegation in diabetes
      mellitus, while PLGA sheets aided the release of AuNP-antagomiR204, which would
      be a promising strategy for titanium implant surface functionalization toward
      better osseointegration.

PMID- 29026304
TI  - Prevention of doxorubicin-induced cardiomyopathy using targeted MaFGF mediated by
      nanoparticles combined with ultrasound-targeted MB destruction.
AB  - The present study seeks to observe the preventive effects of doxorubicin-induced
      cardiomyopathy (DOX-CM) in rats using targeted non-mitogenic acidic fibroblast
      growth factor (MaFGF) mediated by nanoparticles (NP) combined with ultrasound
      targeted MB destruction (UTMD). DOX-CM rats were induced by intraperitoneally
      injected doxorubicin. Six weeks after intervention, the indices from the
      transthoracic echocardiography and velocity vector imaging showed that the left
      ventricular function in the MaFGF-loaded NP (MaFGF-NP) + UTMD group was
      significantly improved compared with the DOX-CM group. The increased
      malondialdehyde and decreased superoxide dismutase were observed in the DOX-CM
      group, while a significant increase in superoxide dismutase and a decrease in
      malondialdehyde were detected in the groups treated with MaFGF-NP + UTMD. From
      the Masson staining, the MaFGF-NP + UTMD group showed a significant difference
      from the DOX-CM group. The cardiac collagen volume fraction and the ratio of the
      perivascular collagen area to the luminal area number of terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labelling positive cells in the MaFGF-NP + UTMD group decreased to 8.9%, 0.55
      fold, compared with the DOX-CM group (26.5%, 1.7-fold). From terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labelling staining, the results showed the strongest inhibition of apoptosis
      progress in MaFGF-NP + UTMD group. The immunohistochemical staining of the TGF
      beta1 in MaFGF-NP + UTMD group reached 3.6%, which was much lower than that of
      the DOX-CM group (12.6%). These results confirmed that the abnormalities,
      including left ventricular dysfunction, myocardial fibrosis, cardiomyocytes
      apoptosis and oxidative stress, could be suppressed by twice weekly MaFGF
      treatments for 6 consecutive weeks (free MaFGF or MaFGF-NP+/UTMD), with the
      strongest improvements observed in the MaFGF-NP + UTMD group. Western blot
      analyses of the heart tissue further revealed the highest pAkt levels, highest
      anti-apoptosis protein (Bcl-2) levels and strongest reduction in proapoptosis
      protein (Bax) levels in the MaFGF-NP + UTMD group. This study confirmed the
      preventive effects of DOX-CM in the rats with MaFGF-NP and UTMD by retarding
      myocardial fibrosis, inhibiting oxidative stress, and decreasing cardiomyocyte
      apoptosis.

PMID- 29026305
TI  - Protective effects on myocardial infarction model: delivery of schisandrin B
      using matrix metalloproteinase-sensitive peptide-modified, PEGylated lipid
      nanoparticles.
AB  - PURPOSE: Schisandrin B (Sch B) is clinically applied for the treatment of
      hepatitis and ischemic disease. However, its clinical efficacy is limited due to
      the poor solubility and low bioavailability. This study aimed to develop matrix
      metalloproteinase (MMP)-sensitive peptide-modified, polyethylene glycol (PEG)
      modified (PEGylated) solid lipid nanoparticles (SLNs) for loading Sch B (MMP-Sch
      B SLNs), and to evaluate the therapeutic effect in the myocardial infarction
      model. METHODS: PEG lipid and MMP-targeting peptide conjugate were synthesized.
      MMP-Sch B SLNs were prepared by solvent displacement technique. The
      physicochemical properties and pharmacokinetics of SLNs were investigated. In
      vivo effects on infarct size was evaluated in rats. RESULTS: The successful
      synthesis of lipid-peptide conjugate was confirmed. MMP-Sch B SLNs had a particle
      size of 130 nm, a zeta potential of 18.3 mV, and a sustained-release behavior.
      Higher heart drug concentration and longer blood circulation times were achieved
      by Sch B loaded SLNs than the drug solution according to the pharmacokinetic and
      biodistribution results. The best therapeutic efficacy was exhibited by MMP-Sch B
      SLNs by reducing the infarction size to the greatest extent. CONCLUSION: The
      modified SLNs may be a good choice for delivery of Sch B for the treatment of
      myocardial infarction.

PMID- 29026306
TI  - Enhanced antifungal activity of voriconazole-loaded nanostructured lipid carriers
      against Candida albicans with a dimorphic switching model.
AB  - Candida commonly adheres to implanted medical devices and forms biofilms. Due to
      the minimal activity of current antifungals against biofilms, new drugs or drug
      delivery systems to treat these persistent infections are urgently needed. In the
      present investigation, voriconazole-loaded nanostructured lipid carriers (Vrc
      NLCs) were formulated for enhanced drug-delivery efficiency to C. albicans to
      increase the antifungal activity of Vrc and to improve the treatment of
      infectious Candida diseases. Vrc-NLCs were prepared by a hot-melt, high-pressure
      homogenization method, and size distribution, zeta-potential, morphology, drug
      encapsulation efficiency, drug loading, and physical stability were
      characterized. The antifungal activity of Vrc-NLCs in vitro was tested during
      planktonic and biofilm growth in C. albicans. The mean particle size of the Vrc
      NLCs was 45.62+/-0.53 nm, and they exhibited spheroid-like morphology, smooth
      surfaces, and zeta-potential of -0.69+/-0.03 mV. Encapsulation efficiency and
      drug loading of Vrc-NLCs were 75.37%+/-2.65% and 3.77%+/-0.13%, respectively.
      Physical stability results revealed that despite the low measured zeta-potential,
      the dispersion of the Vrc-NLCs was stable during their 3-week storage at 4
      degrees C. The minimum inhibitory concentration of Vrc-NLCs was identical to that
      of Vrc. However, the inhibition rate of Vrc-NLCs at lower concentrations was
      significantly higher than that of Vrc during planktonic growth in C. albicans in
      yeast-extract peptone dextrose medium. Surprisingly, Vrc-NLCs treatment reduced
      cell density in biofilm growth in C. albicans and induced more switches form
      hyphal cells to yeast cells compared with Vrc treatment. In conclusion, Vrc-NLCs
      maintain antifungal activity of Vrc and increase antifungal drug-delivery
      efficiency to C. albicans. Therefore, Vrc-NLCs will greatly contribute to the
      treatment of infectious diseases caused by C. albicans.

PMID- 29026307
TI  - Porous Se@SiO2 nanospheres treated paraquat-induced acute lung injury by
      resisting oxidative stress.
AB  - Acute paraquat (PQ) poisoning is one of the most common forms of pesticide
      poisoning. Oxidative stress and inflammation are thought to be important
      mechanisms in PQ-induced acute lung injury (ALI). Selenium (Se) can scavenge
      intracellular free radicals directly or indirectly. In this study, we
      investigated whether porous Se@SiO2 nanospheres could alleviate oxidative stress
      and inflammation in PQ-induced ALI. Male Sprague Dawley rats and RLE-6TN cells
      were used in this study. Rats were categorized into 3 groups: control (n=6), PQ
      (n=18), and PQ + Se@SiO2 (n=18). The PQ and PQ + Se@SiO2 groups were randomly and
      evenly divided into 3 sub-groups according to different time points (24, 48 and
      72 h) after PQ treatment. Porous Se@SiO2 nanospheres 1 mg/kg (in the PQ + Se@SiO2
      group) were administered via intraperitoneal injection every 24 h. Expression
      levels of reduced glutathione, malondialdehyde, superoxide dismutase, reactive
      oxygen species (ROS), nuclear factor-kappaB (NF-kappaB), phosphorylated NF-kappaB
      (p-NF-kappaB), tumor necrosis factor-alpha and interleukin-1beta were detected,
      and a histological analysis of rat lung tissues was performed. The results showed
      that the levels of ROS, malondialdehyde, NF-kappaB, p-NF-kappaB, tumor necrosis
      factor-alpha and interleukin-1beta were markedly increased after PQ treatment.
      Glutathione and superoxide dismutase levels were reduced. However, treatment with
      porous Se@SiO2 nanospheres markedly alleviated PQ-induced oxidative stress and
      inflammation. Additionally, the results from histological examinations and wet-to
      dry weight ratios of rat lung tissues showed that lung damage was reduced after
      porous Se@SiO2 nanosphere treatment. These data indicate that porous Se@SiO2
      nanospheres may reduce NF-kappaB, p-NF-kappaB and inflammatory cytokine levels by
      inhibiting ROS in PQ-induced ALI. This study demonstrates that porous Se@SiO2
      nanospheres may be a therapeutic method for use in the future for PQ poisoning.

PMID- 29026309
TI  - Predicting treatment outcomes of major depressive disorder by early improvement
      in painful physical symptoms: a pooled analysis of double-blind, placebo
      controlled trials of duloxetine.
AB  - OBJECTIVE: We determined if early improvement in painful physical symptoms (PPS)
      can be a predictor of remission in the treatment of major depressive disorder
      (MDD). METHODS: We included randomized, double-blind, parallel-group clinical
      trials of duloxetine (40-60 mg/day) versus placebo for the acute treatment of MDD
      with associated PPS. Only those studies using the Montgomery-Asberg Depression
      Rating Scale (MADRS) and the Brief Pain Inventory - Short Form (BPI-SF) were
      included. Three studies met all criteria and included male or female outpatients
      aged >=18 years who met the diagnostic criteria for MDD, had a MADRS total score
      >=20, and had at least moderate pain (BPI-SF average pain score >=3). Positive
      predictive values (PPVs) and negative predictive values (NPVs) of early
      improvement in PPS for remission were analyzed. PPVs were the proportion of
      patients with remission (MADRS total score <=10) at week 8 out of patients who
      experienced early improvement in BPI-SF average pain score (>=30% decrease from
      baseline at week 1, 2, or 4). NPVs were the proportion of patients without
      remission (MADRS total score >10) at week 8 out of patients who did not
      experience early improvement in PPS. RESULTS: Data from 1,320 patients were
      analyzed (duloxetine N=641 and placebo N=679). The overall remission (MADRS total
      score <=10 at week 8) rate for the duloxetine group was significantly higher than
      the placebo group (38.5% vs 21.8%; P<0.0001). For both treatment groups, PPVs of
      early improvement in BPI-SF (30% improvement from baseline) were higher than the
      overall remission rate for all weeks examined (weeks 1, 2, and 4); in general,
      NPVs of early improvement in BPI-SF for nonremission were higher than the overall
      nonremission rate. CONCLUSION: Early improvement in PPS can be a useful clinical
      indicator of subsequent treatment outcome for MDD patients with associated PPS.

PMID- 29026308
TI  - Role of poly(epsilon-caprolactone) lipid-core nanocapsules on melanoma-neutrophil
      crosstalk.
AB  - Metastatic melanoma is an aggressive cancer with increasing incidence and limited
      therapies in advanced stages. Systemic neutrophilia or abundant neutrophils in
      the tumor contribute toward its worst prognosis, and the interplay of cancer and
      the immune system has been shown in tumor development and metastasis. We recently
      showed the in vivo efficacy of poly(epsilon-caprolactone) lipid-core nanocapsule
      (LNC) or LNC loaded with acetyleugenol (AcE-LNC) to treat B16F10-induced melanoma
      in mice. In this study, we investigated whether LNC or AcE-LNC toxicity could
      involve modifications on crosstalk of melanoma cells and neutrophils. Therefore,
      melanoma cells (B16F10) were pretreated with vehicle, LNC, AcE or AcE-LNC for 24
      h, washed and, further, cocultured for 18 h with peritoneal neutrophils obtained
      from C57Bl/6 mice. Melanoma cells were able to internalize the LNC or AcE-LNC
      after 2 h of incubation. LNC or AcE-LNC pretreatments did not cause melanoma
      cells death, but led melanoma cells to be more susceptible to death in serum
      deprivation or hypoxia or in the presence of neutrophils. Interestingly, the
      production of reactive oxygen species (ROS), which causes cell death, was
      increased by neutrophils in the presence of LNC- and AcE-LNC-pretreated melanoma
      cells. LNC or AcE-LNC treatments reduced the concentration of transforming growth
      factor-beta (TGF-beta) in the supernatant of melanoma cells, a known factor
      secreted by cancer cells to induce pro-tumoral actions of neutrophils in the
      tumor microenvironment. In addition, we found reduced levels of pro-tumoral
      chemical mediators VEGF, arginase-1, interleukin-10 (IL-10) and matrix
      metalloproteinase-9 (MMP-9) in the supernatant of LNC or AcE-LNC-pretreated
      melanoma cells and cocultured with neutrophils. Overall, our data show that the
      uptake of LNC or AcE-LNC by melanoma cells affects intracellular mechanisms
      leading to more susceptibility to death and also signals higher neutrophil
      antitumoral activity.

PMID- 29026310
TI  - Laser interstitial thermal therapy for the treatment of epilepsy: evidence to
      date.
AB  - Medically intractable epilepsy is associated with increased morbidity and
      mortality. For those with focal epilepsy and correlated electrophysiological or
      radiographic features, open surgical resection can achieve high rates of seizure
      control, but can be associated with neurologic deficits and cognitive effects.
      Recent innovations have allowed for more minimally invasive methods of surgical
      seizure control such as magnetic resonance-guided laser interstitial therapy
      (MRgLITT). MRgLITT achieves the goal of ablating seizure foci while preserving
      neuropsycho-logical function and offering real-time feedback and monitoring of
      tissue ablation. This review summarizes the utilization of MRgLITT for mesial
      temporal lobe epilepsy and other seizure disorders. Overall, the efficacy of
      MRgLITT is comparable to that of open surgery and offers a less invasive approach
      in patients with significantly less morbidity.

PMID- 29026311
TI  - Artesunate prevents rats from the clozapine-induced hepatic steatosis and
      elevation in plasma triglycerides.
AB  - Clozapine is an atypical antipsychotic with therapeutic efficacy in treatment
      resistant schizophrenia patients and low incidence of extrapyramidal side
      effects. However, the use of clozapine has been limited by its adverse effects on
      metabolism. Artesunate is a semisynthetic derivative of artemisinin and was shown
      to decrease the plasma cholesterol and triglyceride in rabbits and rats in recent
      studies. The aim of this study was to examine possible effects of artesunate on
      the clozapine-induced metabolic alterations in rats given saline, clozapine,
      artesunate, or clozapine plus artesunate for 6 weeks. The clozapine group showed
      significantly high plasma levels of triglyceride, hepatic steatosis, and fibrosis
      along with high levels of C-reactive protein, alanine aminotransferase, and
      aspartate aminotransferase compared to the saline group. But the treatment had no
      effect on weight gain and caused no hyperglycemia, hyperinsulinemia, and
      behavioral changes in the rats. More significantly, these clozapine-induced
      changes were not seen in rats coadministered with clozapine plus artesunate.
      These results added evidence supporting psychiatrists to try add-on treatment of
      artesunate in schizophrenia patients to ameliorate clozapine-induced adverse
      metabolic effects.

PMID- 29026312
TI  - Robot-assisted versus conventional laparoscopic operation in anus-preserving
      rectal cancer: a meta-analysis.
AB  - OBJECTIVE: The aim of this meta-analysis is to provide recommendations for
      clinical practice and prevention of postoperative complications, such as
      circumferential resection margin (CRM) involvement, and compare the amount of
      intraoperative bleeding, safety, operative time, recovery, outcomes, and clinical
      significance of robot-assisted and conventional laparoscopic procedures in anus
      preserving rectal cancer. METHODS: A literature search (PubMed) was performed to
      identify biomedical research papers and abstracts of studies comparing robot
      assisted and conventional laparoscopic procedures. We attempted to obtain the
      full-text link for papers published between 2000 and 2016, and hand-searched
      references for relevant literature. RevMan 5.3 software was used for the meta
      analysis. RESULTS: Nine papers (949 patients) were eligible for inclusion; there
      were 473 patients (49.8%) in the robotic group and 476 patients (50.2%) in the
      laparoscopic group. According to the data provided in the literature, seven
      indicators were used to complete the evaluation. The results of the meta-analysis
      suggested that robot-assisted procedure was associated with lower intraoperative
      blood loss (mean difference [MD] -41.15; 95% confidence interval [CI] -77.51, 
      4.79; P=0.03), lower open conversion rate (risk difference [RD] -0.05; 95% CI 
      0.09, -0.01; P=0.02), lower hospital stay (MD -1.07; 95% CI -1.80, -0.33;
      P=0.005), lower overall complication rate (odds ratio 0.58; 95% CI 0.41, 0.83;
      P=0.003), and longer operative time (MD 33.73; 95% CI 8.48, 58.99; P=0.009)
      compared with conventional laparoscopy. There were no differences in the rate of
      CRM involvement (RD -0.02; 95% CI -0.05, 0.01; P=0.23) and days to return of
      bowel function (MD -0.03; 95% CI -0.40, 0.34; P=0.89). CONCLUSION: The Da Vinci
      robot was superior to laparoscopy with respect to blood loss, open conversion,
      hospital stay, and postoperative complications during anus-preserving rectal
      cancer procedures; however, conventional laparoscopy had an advantage regarding
      operative time. The remaining indicators (CRMs and recovery from intestinal
      peristalsis) did not differ.

PMID- 29026313
TI  - Pneumonitis and pneumonitis-related death in cancer patients treated with
      programmed cell death-1 inhibitors: a systematic review and meta-analysis.
AB  - PURPOSE: We conducted a meta-analysis of published clinical trials to determine
      the relationship between the risks of pneumonitis and pneumonitis-related death
      and programmed cell death-1 (PD-1) inhibitor treatment in patients with cancer.
      MATERIALS AND METHODS: We examined clinical trials from the Medline and Google
      Scholar databases. Data from original studies and review articles were also cross
      referenced and evaluated. Randomized Phase II and Phase III trials of
      pembrolizumab and nivolumab treatment in patients with cancer were eligible for
      the analysis. Information about the participants, all-grade and high-grade
      pneumonitis, and pneumonitis-related death was extracted from each study and
      analyzed. RESULTS: After the exclusion of ineligible studies, 12 clinical trials
      were included in the analysis. The odds ratio (OR) for all-grade pneumonitis
      after PD-1 inhibitor treatment was 4.59 (95% confidence interval [CI]: 2.51-8.37;
      P<0.00001), and the OR for high-grade pneumonitis after PD-1 inhibitor treatment
      was 3.83 (95% CI: 1.54-9.48; P=0.004). The OR for pneumonitis-related death after
      PD-1 inhibitor treatment was 2.47 (95% CI: 0.41-14.81; P=0.32). Moreover, the OR
      for all-grade pneumonitis after nivolumab/ipilimumab combination therapy versus
      nivolumab monotherapy was 3.54 (95% CI: 1.52-8.23; P=0.003), and that for high
      grade pneumonitis after nivolumab/ipilimumab combination therapy versus nivolumab
      monotherapy was 2.35 (95% CI: 0.45-12.13; P=0.31). Treated cancer appeared to
      have no effect on the risk of pneumonitis. CONCLUSION: Our data showed that PD-1
      inhibitors were associated with increased risks of all-grade and high-grade
      pneumonitis compared with chemotherapy or placebo controls in patients with
      cancer. However, we noted no significant difference between patients treated with
      a PD-1 inhibitor and patients treated with control regimens with respect to the
      risk of pneumonitis-related death.

PMID- 29026314
TI  - Facial palsy: what can the multidisciplinary team do?
AB  - The functional and psychosocial impact of facial paralysis on the patient is
      significant. In response, a broad spectrum of treatment options exist and are
      provided by a multitude of health care practitioners. The cause and duration of
      the facial weakness can vary widely and the optimal care pathway varies. To
      optimize patient outcome, those involved in the care of patients with facial
      palsy should collaborate within comprehensive multidisciplinary teams (MDTs). At
      an international level, those involved in the care of patients with facial
      paralysis should aim to create standardized guidelines on which outcome domains
      matter most to patients to aid the identification of high quality care. This
      review summarizes the causes and treatment options for facial paralysis and
      discusses the subsequent importance of multidisciplinary care in the management
      of patients with this condition. Further discussion is given to the extended role
      of the MDT in determining what constitutes quality in facial palsy care to aid
      the creation of accepted care pathways and delineate best practice.

PMID- 29026315
TI  - A model to facilitate collaborative social support for pregnant students in
      secondary schools.
AB  - Pregnancy among secondary school students remains a public health problem and is
      associated with school dropout as well as poor maternal and child health
      outcomes. Schools in South Africa no longer expel pregnant students as was the
      case before 2000. Instead, the government encourages them to remain in class to
      complete their education, but pregnant students often face stigma, and some drop
      out of school as a result. To remain in class and access antenatal care, pregnant
      students require social support from teachers, parents and professional nurses.
      Unfortunately, teachers, parents and professional nurses support pregnant
      students on an ad hoc basis, and this calls for a model to facilitate
      collaborative social support. The purpose of this paper is to present and
      describe a model to facilitate collaborative social support for pregnant students
      attending secondary schools in South Africa, using the model description steps of
      Chinn and Kramer. The model is designed as a tool to enable pregnant students to
      remain in school, attend antenatal care and in the end, deliver healthy babies.
      The professional nurse, as a member and leader of the school health team which
      visits secondary schools to provide a package of school health services, is the
      agent or facilitator of the model.

PMID- 29026316
TI  - Clinical effects of autologous cytokine-induced killer cell-based immunotherapy
      in the treatment of endometrial cancer: a case report and literature review.
AB  - Endometrial cancer is the most prevalent gynecological malignancy in the USA, and
      its treatment involves surgery, chemotherapy, and radiotherapy. Cytokine-induced
      killer (CIK) cell-based treatments have shown antitumor activity against several
      solid tumors. However, to the best of our knowledge, there are no reports yet of
      CIK immunotherapy in the treatment of endometrial cancer, and consequently,
      little is known about its efficacy and safety. Here, we report a case of an
      endometrial cancer patient receiving a combination treatment with CIK cells
      immunotherapy and chemotherapy. Assessment for clinical features was carried out
      after every two cycles of CIK immunotherapy and chemotherapy. No severe toxicity
      was observed after infusion of CIK cells. After 4 cycles of treatment, the
      patient achieved complete response and showed elevated Karnofsky Performance
      Status scores with an overall survival time of 13.6 months. The combination
      therapy improved the quality of life and prolonged patient survival time, which
      suggested that CIK cell therapy might be a potentially beneficial option for
      endometrial cancer.

PMID- 29026317
TI  - High expression of Sam68 in sacral chordomas is associated with worse clinical
      outcomes.
AB  - Src-associated in mitosis of 68 kDa (Sam68), also known as KHDRBS1 (KH domain
      containing, RNA-binding, signal transduction-associated 1), is a member of the
      signal transduction and activation of RNA family. Previous studies have
      demonstrated that the aberrant expression of Sam68 is associated with the
      progression and prognosis of a variety of cancers, but little is known about its
      expression and role in chordomas, which are rare and aggressive bone neoplasms.
      In this study, we analyzed 40 tumor tissues and 20 distant normal tissues
      obtained from 40 patients with sacral chordoma using immunohistochemistry, and
      observed the expression of Sam68 was significantly upregulated in sacral
      chordomas compared with normal tissues (P=0.001). A positive correlation between
      the expression of Sam68 and the cell proliferation index Ki-67 was determined
      using Spearman's rank correlation test (gamma =0.599, P<0.001). In addition, high
      expression of Sam68 was significantly associated with surrounding muscle invasion
      (P<0.001). Moreover, Kaplan-Meier curves showed that patients with overexpressed
      Sam68 had shorter local recurrence-free survival time (P<0.001). Lastly,
      multivariate analysis indicated that Sam68 is an independent prognostic factor
      for the local recurrence-free survival of sacral chordomas (hazard ratio =5.929,
      95% CI: 1.092-32.188, P=0.039). Our findings suggest the use of Sam68 as a
      predictor for the recurrence of sacral chordomas.

PMID- 29026318
TI  - RNAi-mediated knockdown of CAIX enhances the radiosensitivity of nasopharyngeal
      carcinoma cell line, CNE-2.
AB  - Although radiotherapy remains the most powerful as well as the primary treatment
      modality for nasopharyngeal carcinoma (NPC), approximately 20% of NPC patients
      still have local recurrence. Carbonic anhydrase IX (CAIX)-related signaling
      pathways that mediate radioresistance have been found in various kinds of cancer.
      However, the role of CAIX in NPC radioresistance is still unknown. In this study,
      we investigated the effect of CAIX silencing on sensitization to ionizing
      radiation in NPC by using Lipofectamine 2000, which delivers small interfering
      ribonucleic acid (siRNA) that targets CAIX. Results showed that Lipofectamine
      2000 effectively delivered siRNA into the CNE-2 cells, which resulted in the
      decrease of CAIX expression and cell viability, decrease in cell proliferation
      and colony formation, and increase in the number of CNE-2 cells stuck in the G2/M
      phase of the cell cycle upon induction of ionizing radiation. Increased
      sensitivity of radiotherapy in CNE-2 cells under hypoxic conditions was
      correlated with the suppression of CAIX. Cells treated with irradiation in
      addition to CAIX-siRNA1 demonstrated reduced radiobiological parameters (survival
      fraction at 2 Gy [SF2]) compared with those treated with irradiation only, with a
      sensitization-enhancing ratio of 1.47. These findings suggest that CAIX can be a
      promising therapeutic target for the treatment of radioresistant human NPC.

PMID- 29026319
TI  - Current advances of long non-coding RNA highly upregulated in liver cancer in
      human tumors.
AB  - Long non-coding RNAs (lncRNAs) are a group of non-coding RNAs (ncRNAs) >200
      nucleotides in length that govern diverse biological processes. Recent evidence
      suggests that lncRNAs are involved in cancer cell proliferation, apoptosis,
      invasion, migration, and metastasis. Dysregulation of lncRNAs has been observed
      in various tumors, and lncRNAs act as oncogenes or tumor suppressors in these
      malignancies. It has been revealed that lncRNA highly upregulated in liver cancer
      (HULC) is tightly correlated with a number of cancers such as hepatocellular
      carcinoma, gastric cancer, colorectal cancer, osteosarcoma, and diffuse large B
      cell lymphoma. Depletion of HULC suppressed cancer cell proliferation, migration,
      and invasion and induced apoptosis. Additionally, HULC may function as a
      diagnostic biomarker and prognostic indicator for some tumors. In this review, we
      summarize the current knowledge of the role of HULC in cancer progression and the
      clinical management of human cancers.

PMID- 29026320
TI  - Quercetin inhibits epithelial-mesenchymal transition, decreases invasiveness and
      metastasis, and reverses IL-6 induced epithelial-mesenchymal transition,
      expression of MMP by inhibiting STAT3 signaling in pancreatic cancer cells.
AB  - Quercetin, a flavone, is multifaceted, having anti-oxidative, anti-inflammatory,
      and anticancer properties. In the present study, we explored the effects of
      quercetin on the epithelial-mesenchymal transition (EMT) and invasion of
      pancreatic cancer cells and the underlying mechanisms. We noted that quercetin
      exerted pronounced inhibitory effects in PANC-1 and PATU-8988 cells. Moreover,
      quercetin inhibited EMT and decreased the secretion of matrix metalloproteinase
      (MMP). Meanwhile, we determined the activity of STAT3 after quercetin treatment.
      STAT3 phosphorylation decreased following treatment with quercetin. We also used
      activating agent of STAT3, IL-6, to induce an increase in cell malignancy and to
      observe the effects of treatment with quercetin. As expected, the EMT and MMP
      secretion increased with activation of the STAT3 signaling pathway, and quercetin
      reversed IL-6-induced EMT, invasion, and migration. Therefore, our results
      demonstrate that quercetin triggers inhibition of EMT, invasion, and metastasis
      by blocking the STAT3 signaling pathway, and thus, quercetin merits further
      investigation.

PMID- 29026321
TI  - Characteristics and mutation analysis of Ph-positive leukemia patients with T315I
      mutation receiving tyrosine kinase inhibitors.
AB  - BACKGROUND: TKIs are the first-line treatment for patients with Ph-positive (Ph+)
      leukemia. However, drug resistance is frequently observed, mainly due to
      mutations within the breakpoint cluster region-Abelson leukemia virus (BCR-ABL)
      kinase domain. The T315I substitution confers complete resistance to TKIs. The
      aim of this study was to analyze the clinical characteristics of 17 patients with
      T315I mutation after TKI treatment and provide a basis for prognosis. PATIENTS
      AND METHODS: The clinical data of 17 TKI-resistant Ph+ leukemia patients who were
      found to have a ABL kinase domain mutation from September 2008 to January 2017
      were collected. Karyotypes and BCR-ABL fusion gene were analyzed by R-banding and
      fluorescence in situ hybridization, respectively. Total RNA was extracted by
      TRIzol reagent, and the ABL kinase domain mutation was detected by direct
      sequencing. RESULTS: A total of 17 patients reached effective remission including
      major molecular response and complete cytogenetic response. However, all the
      patients subsequently developed a T315I mutation after treatment with TKIs. The
      rate of the BCR-ABL fusion gene in most of the patients who developed the T315I
      mutation was significantly higher than that before the mutation. At initial
      diagnosis, patients average platelet count was 149.7*109/L, whereas the average
      platelet count was only 53.88*109/L after the T315I mutation (P<0.01). The
      results also showed that the survival time of patients with a high proportion of
      blast cells or a high number of white blood cells was obviously shortened.
      CONCLUSION: Patients platelet count decreased when detected with the T315I
      mutation compared with the initial diagnosis. Combined use of different TKIs and
      complex chromosomal karyotypes may promote the development of the T315I mutation.
      When the ratio of blast cells was >50% and the number of white blood cells was
      >20*109/L, poor survival prognosis was observed.

PMID- 29026322
TI  - Molecular classification of esophagogastric junction carcinoma correlated with
      prognosis.
AB  - A novel molecular classification of gastric cancer by the Asian Cancer Research
      Group (ACRG) is a potential advance in diagnosis and treatment, and it helps to
      determine prognosis. The use of immunohistochemistry (IHC) rather than gene
      expression analysis to determine tumor subtypes was evaluated with the aim of
      determining the feasibility of using the ACRG molecular classification. A total
      of 69 esophagogastric junction (EGJ) carcinomas were classified as microsatellite
      instable (MSI, 17.40%, 12 of 69), microsatellite stable with markers of
      epithelial-to-mesenchymal transition (MSS/EMT, 18.84%, 13 of 69), microsatellite
      stable with active tumor protein 53 (MSS/TP53+, 27.53%, 19 of 69), and
      microsatellite stable with inactive TP53 (MSS/TP53-, 36.23%, 25 of 69). The
      molecular classification did not significantly correlate with anyone of the
      clinicopathological characteristics of the EGJ carcinoma patients, including age,
      gender, depth of tumor invasion, the presence of lymph node metastasis,
      histologic grade, and p-TNM stage of the American Joint Committee on Cancer
      (P>0.05). Kaplan-Meier survival analysis and log rank tests showed that molecular
      classification, histologic grade, p-TNM stage, and postoperative adjuvant
      chemotherapy were significantly associated with overall survival (OS; P<0.05).
      MSI tumors had the best overall prognosis followed by MSS/TP53- and MSS/TP53+.
      MSS/EMT tumors had the worst overall prognosis. Multivariate analysis revealed
      that histologic grade (hazard ratio [HR] =2.216, 95% CI =1.202-4.086), p-TNM
      stage (HR =2.216, 95% CI =1.202-4.086), and molecular subtype (HR =2.216, 95% CI
      =1.202-4.086) were independently associated with OS. The preliminary results
      suggested that the ACRG molecular classification may be a valuable independent
      prognostic marker for EGJ carcinoma patients and could be performed by IHC
      analysis.

PMID- 29026324
TI  - Update of the budget impact analysis of the simplification to atazanavir +
      ritonavir + lamivudine dual therapy of HIV-positive patients receiving atazanavir
      based triple therapies in Italy starting from data of the Atlas-M trial.

PMID- 29026323
TI  - Diagnostic accuracy of Xpert MTB/RIF assay for musculoskeletal tuberculosis: a
      meta-analysis.
AB  - OBJECTIVES: Xpert MTB/RIF assay, a rapid and automated real-time nucleic acid
      amplification test, has been reported for the diagnosis of musculoskeletal
      tuberculosis (TB) in current years. This meta-analysis aims to determine the
      diagnostic accuracy of Xpert for the detection of musculoskeletal TB and
      rifampicin (RIF) resistance. METHODS: We searched PubMed, Embase, China National
      Knowledge Infrastructure, and Wanfang for original articles published up to 1st
      June 2017 to identify studies in which the Xpert assay was applied to diagnose
      musculoskeletal TB. Pooled estimates were calculated using a random-effects model
      or a fixed-effects model according to heterogeneity. Summary receiver operating
      characteristic curves and the area under the curve (AUC) were used to summarize
      overall diagnostic performance. Deeks' test was performed to evaluate potential
      publication bias. RESULTS: Twelve studies were identified with a pooled
      sensitivity and specificity of respectively 0.81 (95% confidence interval [CI]
      0.78-0.83) and 0.83 (95% CI 0.80-0.86) of Xpert for the diagnosis of
      musculoskeletal TB. Xpert was highly sensitive (0.89, 95% CI 0.79-0.95) and
      highly specific (0.96, 95% CI 0.92-0.98) in detecting RIF resistance. AUC (over
      0.9) suggested a relatively high level of overall diagnostic accuracy of Xpert
      for detecting musculoskeletal TB and RIF resistance. Prevalence and reference
      standard were indicated to be sources of heterogeneity between studies. No
      publication bias was found. CONCLUSION: This study provides available evidence of
      the rapid and effective role of Xpert in diagnosing musculoskeletal TB and
      detecting RIF resistance.

PMID- 29026325
TI  - Laparoscopic esophageal myotomy versus pneumatic dilation in the treatment of
      idiopathic achalasia: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Achalasia is a primary esophageal motility disorder of unknown
      etiology associated with abnormalities in peristalsis and lower esophageal
      sphincter relaxation. The disease is incurable; however, definitive treatment
      procedures like pneumatic dilation (PD)/balloon dilation and laparoscopic
      esophageal myotomy (LEM) are performed to relieve dysphagia and related symptoms.
      Currently, there is paucity of data comparing the outcomes of these procedures.
      The aim of this meta-analysis is to compare the short- and long-term success
      rates of PD and LEM. METHODS: A thorough systematic search of PubMed, Scopus,
      clinicaltrials.gov, and Cochrane library was conducted for randomized controlled
      trials (RCTs) comparing the outcomes of PD versus LEM in the treatment of
      achalasia. The Mantel-Haenszel method and random effect model were used to
      analyze the data. RCTs with outcome data at 3-month, 1-year, and 5-year intervals
      were analyzed. RESULTS: A total of 437,378 and 254 patients at 3-month, 1-year,
      and 5-year intervals were analyzed for outcome data. At 3 months and 1 year, PD
      was not as effective as LEM (odds ratio [OR]: 0.50; confidence interval [CI] 0.31
      0.82; P = 0.009 and OR: 0.47; CI 0.22-0.99; P = 0.21) but at 5 years, one
      procedure was non-inferior to the other (OR: 0.62; 0.33-1.19; P = 0.34).
      CONCLUSION: PD was as effective as LEM in relieving symptoms of achalasia in the
      long-term.

PMID- 29026326
TI  - Tacrolimus versus anti-tumor necrosis factor agents for steroid-refractory active
      ulcerative colitis based on the severity of endoscopic findings: a single-center,
      open-label cohort study.
AB  - BACKGROUND AND AIMS: At Saitama Medical Center, for remission induction in active
      ulcerative colitis (UC) patients with endoscopic evidence of severe disease, we
      tend to preferentially use tacrolimus (TAC) over anti-tumor necrosis factor (TNF)
      alpha agents. We conducted this study to evaluate the validity of our therapeutic
      strategies. PATIENTS AND METHODS: This retrospective study was conducted in 52
      steroid-refractory active UC patients with a Clinical Activity Index (CAI) score
      of >=7 who were receiving remission induction therapy with TAC or anti-TNF-alpha
      agents. The patients were divided into a TAC treatment group (TAC group, n = 29)
      and an anti-TNF-alpha agent treatment group (anti-TNF group, n = 23). The CAI,
      Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and incidence of events
      (relapse, hospitalization and surgery) were retrospectively analyzed. RESULTS: At
      treatment initiation, the CAI score was 12.6 in the TAC group and 11.5 in the
      anti-TNF group (P = 0.09), while the corresponding values of the UCEIS were 6.5
      and 5.1, respectively (P = 0.0035). The clinical remission rate at 12 weeks was
      55% (65% when only the subgroup that received rapid induction therapy was
      included in the analysis) in the TAC group and 57% in the anti-TNF group, with no
      significant difference. The cumulative event-free rates at 1, 6 and 12 months
      were 65.5%, 39.4%, and 39.4%, respectively, in the TAC group and 95.7%, 77.2% and
      71.7%, respectively, in the anti-TNF group (P = 0.0037). CONCLUSION: Rapid
      induction therapy with TAC tended to be selected for active UC patients with
      endoscopic evidence of severe disease, and the present study supported the
      validity of this therapeutic approach. However, transition to the remission
      maintenance phase was more favorable in the anti-TNF group.

PMID- 29026327
TI  - Characterization and prevalence of spondyloarthritis and peripheral arthritis
      among patients with inflammatory bowel disease.
AB  - BACKGROUND: Joint complaints such as spondyloarthritis and peripheral arthritis
      are the most common extraintestinal manifestations in patients with inflammatory
      bowel disease (IBD); however, the evaluation of these symptoms are poorly
      described. OBJECTIVES: To examine the clinical characteristics and prevalence of
      ankylosing spondylitis (AS) and other joint complaints among patients with IBD.
      METHODS: In a local cohort of patients diagnosed with IBD between 1996 and 2009,
      we performed a retrospective study at the Veterans Affairs Hospital. Patients
      with IBD were identified by International Classification of Diseases, Ninth
      Revision codes and confirmed by chart review. The occurrence of AS, peripheral
      arthritis, and other peripheral and axial joint symptoms were identified.
      RESULTS: We identified 626 patients with IBD between ages 18 and 90 (90% males),
      of whom 57% had ulcerative colitis (UC), 74% were Caucasians, and the mean age at
      diagnosis was 54 (+/-16) years. Among the study population, 108 patients (17%)
      had at least one type of joint pain. Among these 17% with joint pain, 12% had AS,
      43% had peripheral arthritis, 32% had chronic back pain without AS, and 13% had
      other types of joint pain. The overall prevalence of peripheral arthritis among
      patients with IBD was three times higher than that of AS (7% vs 2.1%,
      respectively, OR 3.5; 95% confidence interval [CI] 1.9-6.5; p=0.001). There was
      no difference in the prevalence of AS or peripheral arthritis between patients
      with Crohn's disease and UC. The initial diagnosis of AS occurred after the
      initial diagnosis of IBD in 80% of patients within a mean (SD) period of 5.6 (+/
      6) years. CONCLUSION: Spondyloarthritis among patients with IBD is usually
      diagnosed after the initial diagnosis of IBD. No difference in the prevalence of
      AS or peripheral arthritis was observed by IBD type, age, or race. Recognition
      and understanding of these results will have important implications for the
      management of IBD patients with spondyloarthritis.

PMID- 29026328
TI  - Phosphorylation of STAT proteins by recombinant human IL-6 in immortalized human
      chondrocyte cell lines, T/C28a2 and C28/I2.
AB  - Two immortalized human juvenile chondrocyte cell lines, T/C28a2 and C28/I2, were
      employed to determine the extent to which recombinant human (rh) IL-6, a known
      cytokine activator of the Janus kinase/signal transducers and activators of
      transcription (JAK/STAT) pathway in many cell types, caused STAT proteins to be
      phosphorylated. The results showed that STAT3 was constitutively phosphorylated
      in the absence of rhIL-6 in T/C28a2 chondrocytes. However, C28/I2 chondrocytes
      treated with rhIL-6 caused STAT1, STAT3, and STAT5 to be phosphorylated without
      altering total unphosphorylated STAT proteins. STAT3 phosphorylation in response
      to rhIL-6 in T/C28a and C28/I2 chondrocytes was efficiently blocked by the JAK3
      selective inhibitor WHI-P131 (Janex-1) and by soluble IL-6 receptor-alpha (sIL
      6R). However, the combination of rhIL-6 and ruxolitinib, a JAK1/JAK2-selective
      inhibitor, was a less effective inhibitor of STAT protein activation. These
      findings showed that rhIL-6 activated STAT proteins in the C28/I2 chondrocyte
      cell line. STAT protein phosphorylation could be blocked by a JAK3-selective
      inhibitor or by the combination of rhIL-6 and sIL-6R.

PMID- 29026329
TI  - Pharmacogenomic testing: aiding in the management of psychotropic therapy for
      adolescents with autism spectrum disorders.
AB  - Adolescents with autism have higher rates of anxiety than the general adolescent
      population. They often struggle to express psychological symptoms verbally where
      their symptoms may manifest as withdrawal and agitation. Adolescent patients with
      autism have higher rates of polypharmacy and high-risk psychiatric medication use
      (eg, atypical antipsychotics) than other patients with psychiatric illness.
      Primary care pediatricians are at the front lines of psychiatric management for
      patients with autism. Yet, they have inadequate access to pediatric psychiatry
      for complex medication management. Pharmacogenomic testing can provide
      personalized drug metabolism profiles for a majority of psychotropic medications.
      Primary care based pharmacogenomic testing for adolescents with autism on one or
      more psychiatric medications may help individualize and optimize complex
      medication regimens, while promoting drug safety.

PMID- 29026330
TI  - Parecoxib relieves pain and has an opioid-sparing effect following major
      gastrointestinal surgery.
AB  - PURPOSE: Parecoxib provides analgesia following a variety of surgeries, including
      minor gastrointestinal procedures. To our knowledge, there is no data on
      parecoxib following major gastrointestinal surgery. This study assessed the
      efficacy and opioid-sparing effects of parecoxib following major gastrointestinal
      surgeries. PATIENTS AND METHODS: Patients in this analysis were a subset from a
      large, randomized, double-blind, placebo-controlled trial of parecoxib following
      noncardiac surgeries and consisted of those undergoing a variety of major
      gastrointestinal surgeries via laparotomy. Pain, pain interference with function,
      supplemental opioid utilization, opioid-related symptoms, and Patient/Physician
      Global Evaluation of Study Medication were compared between placebo and parecoxib
      groups in the 2-3 days following surgery. RESULTS: Significantly (p<0.001) lower
      pain scores were observed in the parecoxib group (n=111), relative to placebo
      (n=126), on Day 2 (-33%) and Day 3 (-35%). Pain interference with function scores
      was also significantly (p<0.001) lower among patients receiving parecoxib
      compared with placebo on Day 2 (-29%) and Day 3 (-36%). At 24, 48, and 72 hours,
      the cumulative amount of supplemental morphine consumed was 45%, 41%, and 40%
      less in patients receiving parecoxib compared with placebo (all p<0.001). The
      risk of experiencing >=1 opioid-related symptoms was also significantly lower
      with parecoxib than with placebo on Day 2 (relative risk=0.75; p<0.001).
      Specifically, the risks of fatigue and drowsiness were significantly (both
      p<0.05) lower in patients receiving parecoxib compared to those receiving
      placebo. Patient and Physician Global Evaluation of Study Medication scores were
      significantly better in the parecoxib group than in the placebo group (p<0.001).
      CONCLUSION: This study is the first to demonstrate that multiple-dose parecoxib,
      initiated upon recovery from anesthesia, provides analgesia and opioid-sparing
      effects following a variety of major gastrointestinal surgeries employing
      laparotomy.

PMID- 29026332
TI  - Ultrasound-guided methotrexate injection for De Quervain disease of the wrist:
      what lies beyond the horizon?
AB  - De Quervain disease (DQVD) is one of the most common causes of lateral wrist pain
      and can lead to significant disability. The current case involves a right-handed,
      middle-aged, female patient with severe lateral wrist pain due to DQVD. Her pain
      was not responsive to oral non-steroidal anti-inflammatory drugs, rehabilitation,
      and repeated corticosteroid injections. Because she refused surgical
      intervention, we performed ultrasound-guided methotrexate injections (four
      times). After the injections, dramatic pain relief, functional improvement, and
      reduction of the thickness of the retinaculum and tendons in the first dorsal
      extensor compartment of the wrist were noted. This case report highlights the
      potential usefulness of ultrasound-guided methotrexate injection for recalcitrant
      DQVD of the wrist.

PMID- 29026333
TI  - Analgesic efficacy and safety of epidural oxycodone in patients undergoing total
      hip arthroplasty: a pilot study.
AB  - BACKGROUND AND OBJECTIVES: Oxycodone is poorly studied as an adjuvant to central
      blockades. The aim of this pilot study was to assess the efficacy and safety of
      oxycodone hydrochloride in epidural blockade among patients undergoing total hip
      arthroplasty (THA). PATIENTS AND METHODS: In 11 patients (American Society of
      Anesthesiologists physical status classification system II/III, age range: 59-82
      years), THA was conducted with an epidural blockade using 15 mL 0.25% bupivacaine
      (37.5 mg) with 5 mg oxycodone hydrochloride and sedation with propofol infusion
      at a dose of 3-5 mg/kg/h. After the surgery, patients received ketoprofen at a
      dose of 100 mg twice daily. In the first 24 hours postoperative period, pain was
      assessed by numerical rating scale at rest and on movement; adverse effects (AEs)
      were recorded; and plasma concentrations of oxycodone, noroxycodone, and
      bupivacaine were measured. RESULTS: The administration of epidural oxycodone at a
      dose of 5 mg in patients undergoing THA provided analgesia for a mean time of
      10.3+/-4.89 h. In one patient, mild pruritus was observed. Oxycodone did not
      evoke other AEs. Plasma concentrations of oxycodone while preserving analgesia
      were >2.9 ng/mL. Noroxycodone concentrations in plasma did not guarantee
      analgesic effect. CONCLUSION: The administration of epidural oxycodone at a dose
      of 5 mg prolongs the analgesia period to ~10 hours in patients after THA.
      Oxycodone may evoke pruritus. A 5 mg dose of oxycodone hydrochloride used in an
      epidural blockade seems to be a safe drug in patients after THA.

PMID- 29026334
TI  - An investigation into the effect of depth of anesthesia on postoperative pain in
      laparoscopic cholecystectomy surgery: a double-blind clinical trial.
AB  - BACKGROUNDS AND OBJECTIVE: Some studies have shown that deeper anesthesia is more
      effective on postoperative analgesia and reduces the need for sedative drugs.
      This study sought to investigate the effect of depth of anesthesia on
      postoperative pain in laparoscopic cholecystectomy. MATERIALS AND METHODS: In
      this double-blind clinical trial, 60 patients undergoing laparoscopic
      cholecystectomy were randomly divided into two groups: low bispectral index (L
      BIS=35-44) and high bispectral index (H-BIS=45-55). Anesthesia protocol was the
      same for both groups (propofol and remifentanil). The pain intensity (at rest and
      during cough) was evaluated based on the visual analog scale scores in recovery
      and at 8, 16 and 24 hours after surgery. RESULTS: The mean pain score was
      significantly lower in patients in the L-BIS group at all examined times at rest
      and during cough than that in the H-BIS group. The number of patients in need of
      additional sedative drug in the H-BIS group in recovery was significantly more
      than that in the L-BIS group (27 vs 18 patients, P=0.007). The incidence of
      nausea in the recovery room 8 hours after the surgery was significantly less in
      the L-BIS group than that in the H-BIS group, while at 16 and 24 hours, no case
      of nausea was reported in the two groups. CONCLUSION: Given the results of this
      study, it seems that general anesthesia with propofol and remifentanil with L-BIS
      causes less need for additional analgesic drug and less nausea and vomiting
      compared to anesthesia with H-BIS.

PMID- 29026331
TI  - Poorly controlled postoperative pain: prevalence, consequences, and prevention.
AB  - This review provides an overview of the clinical issue of poorly controlled
      postoperative pain and therapeutic approaches that may help to address this
      common unresolved health-care challenge. Postoperative pain is not adequately
      managed in greater than 80% of patients in the US, although rates vary depending
      on such factors as type of surgery performed, analgesic/anesthetic intervention
      used, and time elapsed after surgery. Poorly controlled acute postoperative pain
      is associated with increased morbidity, functional and quality-of-life
      impairment, delayed recovery time, prolonged duration of opioid use, and higher
      health-care costs. In addition, the presence and intensity of acute pain during
      or after surgery is predictive of the development of chronic pain. More effective
      analgesic/anesthetic measures in the perioperative period are needed to prevent
      the progression to persistent pain. Although clinical findings are inconsistent,
      some studies of local anesthetics and nonopioid analgesics have suggested
      potential benefits as preventive interventions. Conventional opioids remain the
      standard of care for the management of acute postoperative pain; however, the
      risk of opioid-related adverse events can limit optimal dosing for analgesia,
      leading to poorly controlled acute postoperative pain. Several new opioids have
      been developed that modulate MU-receptor activity by selectively engaging
      intracellular pathways associated with analgesia and not those associated with
      adverse events, creating a wider therapeutic window than unselective conventional
      opioids. In clinical studies, oliceridine (TRV130), a novel MU-receptor G-protein
      pathway-selective modulator, produced rapid postoperative analgesia with reduced
      prevalence of adverse events versus morphine.

PMID- 29026335
TI  - Challenging the standard of care in advanced melanoma: focus on pembrolizumab.
AB  - The last several years have seen a dramatic rise in the number of effective
      therapies that have been shown to improve survival outcomes for patients with
      advanced melanoma. Among these treatments are the immune checkpoint inhibitors, a
      new class of immunotherapy, that have demonstrated the ability to improve both
      response rates and survival outcomes. Pembrolizumab, an immune checkpoint
      inhibitor that blocks the negative regulatory PD-1 receptor on T-cell
      lymphocytes, has shown improved efficacy compared to standard therapies with an
      acceptable tolerability profile. Additionally, this agent is being evaluated in
      adjuvant and combination trial strategies that have great potential to further
      advance outcomes. This review focuses on the advances that pembrolizumab has made
      in melanoma and what studies are upcoming that could change the future of
      melanoma treatment yet again.

PMID- 29026336
TI  - Factors associated with continuing emergence of beta-thalassemia major despite
      prenatal testing: a cross-sectional survey.
AB  - PURPOSE: Health care initiatives focusing on prenatal testing and premarital
      genetic screening aiming to reduce the incidence of beta-thalassemia have emerged
      during the last decade. In Palestine, 4% of the population are known thalassemia
      carriers with new cases continuing to appear despite the availability of prenatal
      testing. This study aims to identify factors that influence the decision to
      retain or abort fetuses affected by beta-thalassemia in Palestine. METHODS:
      Convenience sampling was used to select 32 women (72 fetuses) who were at risk of
      having a baby with beta-thalassemia. A questionnaire on prenatal testing, test
      results, pregnancy outcomes, and factors influencing the decision to terminate
      the pregnancy were used for this cross-sectional study. The data were analyzed
      using SPSS version 17. RESULTS: Among the fetuses screened, 36 (50%) were
      thalassemia carriers and 20 (28%) had beta-thalassemia; 17 (85%) affected fetuses
      were aborted. Religious beliefs were the most cited reason for opposing abortion
      while prior experience with beta-thalassemia patients and awareness programs
      promoted abortions. Mothers who opted to retain an affected fetus had modest
      educational attainment. Higher educational level was significantly associated
      with the decision to abort an affected fetus (p<0.05). CONCLUSION: A religious
      consensus is needed on the abortion of fetuses affected by beta-thalassemia.
      Improving female education and increasing awareness on thalassemia could help
      reduce the incidence of beta-thalassemia in Palestine and around the world.

PMID- 29026337
TI  - Rate and factors affecting non-exclusive breastfeeding among Thai women under the
      breastfeeding promotion program.
AB  - OBJECTIVE: The objective of this study was to assess the rate of non-exclusive
      breastfeeding and associated factors among Thai women under the Breastfeeding
      Promotion Program. METHODS: This was a prospective descriptive study that
      involved term postpartum women who attended the Breastfeeding Clinic at
      Srinagarind Hospital in Thailand, from April to December 2016. Abstracted data
      included baseline characteristics, obstetric history, breastfeeding history,
      problems in breastfeeding at day 3 and 2 weeks, and feeding status at 12 weeks
      postpartum. Univariate and multivariate logistic regression methods were used to
      determine significant factors predicting non-exclusive breastfeeding. RESULTS: Of
      the 500 postpartum women enrolled in this study, follow-up data at 12 weeks
      postpartum were available for 368 women (73.6%). The rate of non-exclusive
      breastfeeding assessed at 12 weeks postpartum was 26.4% (95% CI 21.9%-31.2%).
      Nipple problems and pain during the first 3 days postpartum and milk storage
      problems at 2 weeks postpartum were the major reasons for non-exclusive
      breastfeeding (69.4% and 59.1%, respectively). The significant independent
      factors that predicted these included patients not having confidence in their
      ability to breastfeed exclusively or not having any intention to do so (OR 7.22;
      95% CI 3.26-14.24), no rooming-in (OR 2.31; 95% CI 1.04-5.12), and low milk
      quantity at 2 weeks postpartum (OR 3.75; 95% CI 1.70-8.29). CONCLUSION: The rate
      of non-exclusive breastfeeding in this study was ~26%, and significant associated
      factors included having lack of confidence/intention, no rooming-in, and low milk
      quantity reported at 2 weeks postpartum.

PMID- 29026338
TI  - Utilization of healthcare services in postpartum women in the Philippines who
      delivered at home and the effects on their health: a cross-sectional analytical
      study.
AB  - BACKGROUND: A low ratio of utilization of healthcare services in postpartum women
      may contribute to maternal deaths during the postpartum period. The maternal
      mortality ratio is high in the Philippines. The aim of this study was to examine
      the current utilization of healthcare services and the effects on the health of
      women in the Philippines who delivered at home. METHODS: This was a cross
      sectional analytical study, based on a self-administrated questionnaire,
      conducted from March 2015 to February 2016 in Muntinlupa, Philippines. Sixty
      three postpartum women who delivered at home or at a facility were enrolled for
      this study. A questionnaire containing questions regarding characteristics,
      utilization of healthcare services, and abnormal symptoms during postpartum
      period was administered. To analyze the questionnaire data, the sample was
      divided into delivery at home and delivery at a facility. Chi-square test,
      Fisher's exact test, and Mann-Whitney U test were used. RESULTS: There were
      significant differences in the type of birth attendant, area of residence,
      monthly income, and maternal and child health book usage between women who
      delivered at home and those who delivered at a facility (P<0.01). There was
      significant difference in the utilization of antenatal checkup (P<0.01) during
      pregnancy, whilst there was no significant difference in utilization of
      healthcare services during the postpartum period. Women who delivered at home
      were more likely to experience feeling of irritated eyes and headaches, and
      continuous abdominal pain (P<0.05). CONCLUSION: Financial and environmental
      barriers might hinder the utilization of healthcare services by women who deliver
      at home in the Philippines. Low utilization of healthcare services in women who
      deliver at home might result in more frequent abnormal symptoms during
      postpartum.

PMID- 29026339
TI  - Possibility of using superoxide dismutase and glutathione peroxidase as
      endometriosis biomarkers.
AB  - OBJECTIVE: To study the possibility of using superoxide dismutase (SOD) and
      glutathione peroxidase (GPx) as combined preoperative biomarkers for
      endometriosis. PARTICIPANTS AND METHODS: Female patients aged between 18 and 45
      years old who came to the Gynecology outpatient clinic, Thammasat University
      Hospital, during September 2013-2016 with the complaint of gynecologic symptoms
      suspected of endometriosis, and who were positively diagnosed with endometriosis,
      were included in this study. All patients underwent conservative laparoscopic
      ovarian cystectomy with histopathological report. The control group consisted of
      healthy females of reproductive age who came to the outpatient clinic. The plasma
      SOD and GPx were measured from blood samples with commercial kits. A receiver
      operating characteristic curve was generated for plasma activity of SOD, GPx, and
      combined tests. The cutoff values were selected at the most appropriate
      sensitivity and specificity. RESULT: All 36 cases were included in this study.
      Mean ages of patients in the patient and control groups were 33.1 and 28.6 years
      old, respectively. SOD and GPx activities of disease and control group were 6.15
      and 8.11, 463.9 and 472.34 nmole/min/mL unit, respectively. The sensitivity and 1
      specificity of the combined test were calculated at 0.78, with sensitivity,
      specificity, accuracy, positive predictive value, and negative predictive value
      being 68.75, 80.77, 76.50, 69.23, and 80.33, respectively. CONCLUSION: A
      combination testing of SOD and GPx can possibly be used as preoperative biomarker
      for endometriosis.

PMID- 29026340
TI  - Economic impact of the use of rifaximin 550 mg twice daily for the treatment of
      overt hepatic encephalopathy in Italy.
AB  - PURPOSE: Hepatic encephalopathy (HE) is associated with a reduced survival, an
      increased risk of hospitalization for recurrences, and a reduced health-related
      quality of life. The purpose of the present economic analysis was to evaluate the
      impact on the Italian National Health Service (INHS) expenditure of the treatment
      with rifaximin 550 mg twice daily (Tixteller(r)/Tixtar(r)) for the reduction of
      the recurrences of overt HE, with respect to the current treatment approach.
      PATIENTS AND METHODS: Costs associated with patients treated with rifaximin 550
      mg twice daily were estimated considering the reduction in hospitalizations for
      HE recurrences revealed by registrative clinical trial (-50%) applied to the
      hospitalization rate (42.5%) emerging from an Italian observational real-world
      study; costs associated with patients not treated with rifaximin were estimated
      based on the hospitalization rate, resulting from the same Italian observational
      study. Sensitivity analyses considering possible different discount levels to
      INHS structures for rifaximin were performed. The INHS perspective for a period
      of 3 years was considered. RESULTS: The treatment with rifaximin 550 mg twice
      daily, although increasing drug costs, is associated with a reduction in
      hospitalizations for HE recurrences that leads to an overall reduction of total
      costs charged to INHS, which could be estimated, based on the forecasted uptake
      of the treatment, at about ?130,000 in the first year, reaching ~?260,000 in the
      third year. Considering a possible discount for rifaximin 550 mg to INHS
      structure of 20%, the total saving at the third year accounts for ~?3,000,000.
      Moreover, a relevant reduction in the number of hospitalizations and bed days is
      associated with rifaximin treatment. CONCLUSION: The treatment with rifaximin 550
      mg twice daily, even if associated with an increase in drug expenditure, results
      in a reduction in total health care costs charged to INHS due to a reduction in
      hospitalizations for HE recurrences.

PMID- 29026341
TI  - Benefits of different postoperative treatments in patients undergoing knee
      arthroscopic debridement.
AB  - PURPOSE: To assess the effectiveness of viscosupplementation or platelet-rich
      plasma (PRP), compared to standard care, for pain relief after knee arthroscopic
      debridement in patients with meniscal pathology and osteoarthritis (OA), under
      normal clinical practice conditions. PATIENTS AND METHODS: We conducted a
      prospective, randomized, evaluator-blind, pilot study. After arthroscopy,
      patients were randomized to receive 1) five injections of HA1
      (Suprahyal(r)/Adant(r)); 2) four injections of HA2 (Orthovisc(r)); 3) three
      injections of HA3 (Synvisc(r)); 4) a single injection of PRP (GPSTM II); or 5)
      standard care (control). Patients were followed up for 18 months. Clinical
      outcomes were evaluated using the Western Ontario and McMaster Universities
      Arthritis Index (WOMAC) at 3, 6, 12, and 18 months. Minimally Clinical Important
      Improvement (MCII), as relative improvement >=20 for pain and function, was also
      calculated. RESULTS: Fifty patients were included. At early follow-up (3 months),
      total WOMAC scores improved in all groups compared to baseline with reductions of
      44.79% (HA1), 24.02% (HA2), 40.38% (HA3), 39.77% (PRP), and 27.64% (control)
      (p=0.002 HA1 compared to HA2). At 18 months, the higher improvement in total
      WOMAC was in HA1 with a 65.20% reduction, followed by PRP (55.01%), HA3 (49.57%),
      and HA2 (29.82%), whereas the control group had a 14.55% increase over baseline
      (p=0.001 control compared to HA1 and HA3). The percentage of patients achieving
      the MCII for both pain and function at 18 months was 100% (HA1), 80% (HA3), 60%
      (HA2), and 60% (PRP), whereas, in the control group, all patients returned to pre
      arthroscopy levels. There were no adverse events attributable to surgery or to
      intraarticular administration. CONCLUSION: Viscosupplementation following
      arthroscopy is more effective than PRP in adequately selected patients with
      meniscal lesions occurring concomitantly with OA. Further controlled studies with
      a larger sample size and/or alternative regimens would be of interest for the
      scientific community.

PMID- 29026342
TI  - Flow visualization over a thick blunt trailing-edge airfoil with base cavity at
      low Reynolds numbers using PIV technique.
AB  - ABSTRACT: In this study, the effect of cutting the end of a thick airfoil and
      adding a cavity on its flow pattern is studied experimentally using PIV
      technique. First, by cutting 30% chord length of the Riso airfoil, a thick blunt
      trialing-edge airfoil is generated. The velocity field around the original
      airfoil and the new airfoil is measured by PIV technique and compared with each
      other. Then, adding two parallel plates to the end of the new airfoil forms the
      desired cavity. Continuous measurement of unsteady flow velocity over the Riso
      airfoil with thick blunt trailing edge and base cavity is the most important
      innovation of this research. The results show that cutting off the end of the
      airfoil decreases the wake region behind the airfoil, when separation occurs.
      Moreover, adding a cavity to the end of the thickened airfoil causes an increase
      in momentum and a further decrease in the wake behind the trailing edge that
      leads to a drag reduction in comparison with the thickened airfoil without
      cavity. Furthermore, using cavity decreases the Strouhal number and vortex
      shedding frequency. GRAPHICAL ABSTRACT: 

PMID- 29026343
TI  - Photothermal stability of biologically and chemically synthesized gold
      nanoprisms.
AB  - We report here the influence of the irradiation with femtosecond laser pulses on
      the gold nanoprisms synthesized using biological and chemical methods. For the
      bio-mediated growth, we used plant extract as a source of reducing, structure
      directing, and stabilizing agents, while for the chemical method, we applied
      three-step protocol, involving chemicals commonly used in the synthesis of
      nanostructures. Exposition of the nanostructures to the laser beam causes
      morphological changes, which affect their extinction spectra. These modifications
      were followed using absorption spectroscopy and transmission electron microscopy.
      The observed effects depend on the applied laser power and excitation wavelength.
      Under resonance conditions, rounding of the tips of triangular nanoparticles and
      transformation towards more stable, spherical form were noticed. These changes
      were faster under higher laser power. Such shape modifications were weaker under
      off-resonance conditions. Moreover, chemically synthesized gold nanoprisms were
      less susceptible to the morphological changes than those obtained using plant
      extract; however, their colloidal stability was disrupted by long-time
      irradiation. Graphical abstract?.

PMID- 29026344
TI  - Convex congruences.
AB  - For an algebra [Formula: see text] belonging to a quasivariety [Formula: see
      text], the quotient [Formula: see text] need not belong to [Formula: see text]
      for every [Formula: see text]. The natural question arises for which [Formula:
      see text]. We consider algebras [Formula: see text] of type (2, 0) where a
      partial order relation is determined by the operations [Formula: see text] and 1.
      Within these, we characterize congruences on [Formula: see text] for which
      [Formula: see text] belongs to the same quasivariety as [Formula: see text]. In
      several particular cases, these congruences are determined by the property that
      every class is a convex subset of A.

PMID- 29026347
TI  - From the Editor's Desk: Well-Being in the Workplace.

PMID- 29026345
TI  - Tolerated drugs in subjects with severe cutaneous adverse reactions (SCARs)
      induced by anticonvulsants and review of the literature.
AB  - BACKGROUND: Anticonvulsant hypersensitivity syndrome represents a rare but
      potentially fatal kind of adverse drug reaction. This clinical picture often
      hampers the flexibility with which alternative anticonvulsants or even other
      classes of drugs are prescribed in these patients, negatively affecting the
      efficacy of treatment and the course of the disease. The aim of this study was to
      analyse a group of six patients with severe cutaneous drug reactions induced by
      anticonvulsants and to report which alternative antiepileptic drugs and which
      drugs of other classes were tolerated. CASE PRESENTATION: A total of six patients
      (2 males and 4 females, age 11-73 years) are described in this study. In all the
      patients the onset of the severe cutaneous drug reactions was 2-4 weeks after
      initiating the anticonvulsant therapy: 2 out of 6 patients presented with a drug
      reaction with eosinophilia and systemic symptoms under therapy with phenytoin; 2
      out of 6 presented with Stevens-Johnson syndrome under therapy with lamotrigine;
      and 2 out of 6 presented with a toxic epidermal necrolysis, one of them under
      therapy with valproic acid, and the other one under therapy with lamotrigine.
      Alternative anticonvulsants tolerated after the reaction were: clonazepam,
      levetiracetam, diazepam, delorazepam and lormetazepam. CONCLUSIONS: In our cases
      we observed that non aromatic anticonvulsants and benzodiazepines were well
      tolerated as alternative treatments in six patients with reactions to aromatic
      anticonvulsivants and that the risk of hypersensitivity reactions to other drug
      classes was not increased as compared to general population.

PMID- 29026348
TI  - Letter to the Editor: Positron Emission Tomography-Positive Pleural-Based Nodule
      Following Talc Pleurodesis.

PMID- 29026346
TI  - Treatment with direct oral anticoagulants in patients with upper extremity deep
      vein thrombosis.
AB  - BACKGROUND: Upper extremity deep vein thrombosis (UEDVT) constitutes around 10%
      of all DVT, and can cause both pulmonary embolism (PE) and postthrombotic
      syndrome (PTS) in the arm. The incidence of secondary UEDVT is increasing due to
      widespread use of central venous catheters in patients with cancer and other
      chronic diseases. The safety and efficacy of using new direct acting oral anti
      coagulants (DOAC) in the treatment of UEDVT has not been systematically
      evaluated. Our aims were to evaulate efficacy, safety, and risk of recurrence of
      venous thromboembolism (VTE) during DOAC treatment in UEDVT patients. METHODS:
      Data from the Swedish national anticoagulation registry (AuriculA) was
      retrospectively evaluated for all 55 patients (27 men aged 23-86 years, and 28
      women aged 18-75 years) treated with DOAC because of UEDVT between 2012 and 2015
      in the southernmost hospital region of Sweden with 1.3 million inhabitants in
      2016. Patients were followed for 6 months. RESULTS: During 6 months after
      institution of DOAC treatment there was one recurrence (2%) of DVT during
      treatment and two (4%) recurrences after cessation of treatment. No patient died,
      whereas one (2%) suffered a clinically relevant nonmajor bleeding. CONCLUSION:
      DOAC can be used in the treatment of UEDVT patients with acceptable efficacy and
      safety.

PMID- 29026349
TI  - Letter to the Editor: A Delayed Diagnosis of Iatrogenic Guidewire Retention After
      Central Line Placement.

PMID- 29026350
TI  - Letter to the Editor: Mobile Technology Can Improve Adherence and Lessen
      Tacrolimus Variability in Patients Receiving Kidney Transplants.

PMID- 29026351
TI  - Clinical Images: Four-Dimensional Computed Tomography-Future of Preoperative
      Parathyroid Adenoma Imaging.

PMID- 29026352
TI  - Bioethics in Practice: Dr Alton Ochsner's Ethics.

PMID- 29026353
TI  - Association of Body Mass Index and Postoperative Acute Kidney Injury in Patients
      Undergoing Laparoscopic Surgery.
AB  - BACKGROUND: Whether the deleterious effects of carbon dioxide pneumoperitoneum on
      the kidneys are exacerbated in the obese population remains unknown. We
      hypothesized that increased body mass index (BMI) is associated with an increased
      incidence of postoperative acute kidney injury (AKI) in patients undergoing
      noncardiac laparoscopic surgery. METHODS: Following institutional review board
      approval, we analyzed data on 8,543 adult patients with American Society of
      Anesthesiologists physical status scores of I-IV who had inpatient noncardiac
      laparoscopic surgery from 2005-2014. Because the exposure (current BMI) is a
      chronic condition, we a priori assumed that diabetes mellitus, hypertension,
      coronary artery disease, and chronic obstructive pulmonary disease might mediate
      the effect of obesity on outcome. Our primary analysis was a proportional odds
      logistic regression model with current BMI as a predictor and AKI as an ordinal
      outcome. RESULTS: After controlling for potential confounding variables, the odds
      of developing a more serious level of AKI was 7% (95% CI 0%, 15%) greater with a
      5-unit increase in BMI (P=0.05). When the analysis was adjusted for the a priori
      mediators in an attempt to estimate the pure effect of BMI on AKI, the result was
      no longer significant (Wald test P=0.35), with the residual effect of BMI of 3%
      (95% CI -4%, 11%). CONCLUSION: We found a marginal association between BMI and an
      increased risk of developing AKI in adult patients after having noncardiac
      laparoscopic surgery. The BMI effect became insignificant when potential mediator
      variables were considered. The association of BMI and AKI after noncardiac
      laparoscopic surgery is likely mediated through components of the metabolic
      syndrome.

PMID- 29026354
TI  - Novel Regional Techniques for Total Knee Arthroplasty Promote Reduced Hospital
      Length of Stay: An Analysis of 106 Patients.
AB  - BACKGROUND: Novel regional techniques, including the adductor canal block (ACB)
      and the local anesthetic infiltration between the popliteal artery and capsule of
      the knee (IPACK) block, provide an alternative approach for controlling pain
      following total knee arthroplasty (TKA). This study compared 3 regional
      techniques (femoral nerve catheter [FNC] block alone, FNC block with IPACK, and
      ACB with IPACK) on pain scores, opioid consumption, performance during physical
      therapy, and hospital length of stay in patients undergoing TKA. METHODS: All
      patients had a continuous perineural infusion, either FNC block or ACB. Patients
      in the IPACK block groups also received a single injection 30-mL IPACK block of
      0.25% ropivacaine. Pain scores and opioid consumption were recorded at
      postanesthesia care unit discharge and again at 8-hour intervals for 48 hours.
      Physical therapy performance was measured on postoperative days (POD) 1 and 2,
      and hospital length of stay was recorded. RESULTS: We found no significant
      differences in the 3 groups with regard to baseline patient demographics.
      Although we observed no differences in pain scores between the 3 groups, opioid
      consumption was significantly reduced in the FNC with IPACK group. Physical
      therapy performance was significantly better on POD 1 in the ACB with IPACK group
      compared to the other 2 groups. Hospital length of stay was significantly shorter
      in the ACB with IPACK group. CONCLUSION: This study demonstrated that an IPACK
      block reduced opioid consumption by providing effective supplemental analgesia
      following TKA compared to the FNC-only technique. ACB with IPACK provided
      equivalent analgesia and improved physical therapy performance, allowing earlier
      hospital discharge.

PMID- 29026355
TI  - Colistin and Polymyxin B Minimal Inhibitory Concentrations Determined by Etest
      Found Unreliable for Gram-Negative Bacilli.
AB  - BACKGROUND: A reliable method of polymyxin B and E (colistin) susceptibility
      testing remains elusive. These drugs diffuse poorly into agar, creating
      potentially inaccurate Etest and disk diffusion results, and testing by these
      methods is not recommended. Broth microdilution is the reference testing method,
      although it can be sometimes difficult to interpret. Currently, when a colistin
      susceptibility test is ordered for a patient in the Ochsner Health System, our
      diagnostic microbiology laboratory performs the Etest. As an in-house quality
      assessment project, we compared colistin and polymyxin B minimal inhibitory
      concentrations (MICs) determined by Etest with MICs determined by broth
      microdilution to evaluate whether colistin MICs are accurately being reported by
      Etest. METHODS: A total of 143 nonduplicate clinical isolates from Ochsner
      patients during 2015-2016 were tested: Acinetobacter baumannii (n=60),
      Pseudomonas aeruginosa (n=44), and Enterobacteriaceae (n=39) (13 Escherichia
      coli, 15 Klebsiella spp, and 11 Enterobacter spp). Colistin and polymyxin B MICs
      were determined by Etest and broth microdilution. RESULTS: Using broth
      microdilution, 16/143 (11%) isolates were nonsusceptible to colistin, and 12/143
      (8%) were nonsusceptible to polymyxin B. With Etest, 4/143 (3%) isolates were
      nonsusceptible to colistin, and 7/143 (5%) were nonsusceptible to polymyxin B.
      Essential agreement of colistin and polymyxin B MICs between broth microdilution
      and Etest was 84/143 (59%) and 87/143 (61%), respectively. Categorical agreement
      for colistin and polymyxin B was 127/143 (89%) and 126/143 (88%), respectively.
      CONCLUSION: We found a high rate of discrepancy between colistin and polymyxin B
      Etest and broth microdilution MICs. Very major errors (colistin/polymyxin B
      susceptible by Etest, colistin/polymyxin B-resistant by broth microdilution) were
      detected in 10% of isolates tested with colistin and 8% of polymyxin B-tested
      isolates. The data from this study confirm that broth microdilution should be
      performed for susceptibility testing of polymyxins.

PMID- 29026356
TI  - Comparison of In-Hospital Maternal Mortality Between Hospital Systems in
      Queensland, Australia and Louisiana, United States.
AB  - BACKGROUND: It is well documented that the American maternal mortality ratio has
      increased during the years 2000-2015. The Australian maternal mortality ratio, in
      contrast, has decreased during the same time period, a trend common among most
      Western countries. METHODS: This study was a retrospective cohort study of cases
      of in-hospital maternal deaths in the Ochsner Health System (Louisiana, United
      States) and the Queensland Health System (Australia) from 1995 to 2013. The aim
      was to determine if American and Australian women have a similar rate of
      preventable maternal death and if the deaths were attributable to the same
      factors. A multidisciplinary team assessed medical records to determine
      preventability. RESULTS: Sixteen eligible medical records were identified in the
      Ochsner Health System and 15 in the Queensland Health System. In the American
      cohort, deaths in the private insurance group (n=5) were least likely to be
      preventable (P=0.003). Australian maternal deaths were less likely to occur among
      women with late or no prenatal care than American maternal deaths; the risk
      difference was 44.5% for all deaths (95% confidence interval [CI]=9.7%, 79.4%;
      P=0.03) and 50.0% for potentially preventable deaths (95% CI=9.3%, 90.6%;
      P=0.04). CONCLUSION: Women from Louisiana, United States and Queensland,
      Australia have similar rates of preventable maternal death. No statistically
      significant factors explained trends in Australian maternal death; American
      maternal mortality was significantly associated with point of entry into prenatal
      care, likely influenced by insurance status. Furthermore, the majority of deaths
      in this group were complicated by hospital systems-based factors.

PMID- 29026357
TI  - Use of Digital Pupillometry to Measure Sedative Response to Propofol.
AB  - BACKGROUND: Digital pupillometry (DP) accurately and precisely measures pupillary
      responses. Little is known about using DP to measure the sedative effect of
      isolated propofol administration. METHODS: We conducted a cross-sectional study
      of 19 adults undergoing moderate sedation with propofol during which we measured
      pupillary changes using DP. RESULTS: Maximum and minimum pupillary diameters
      decreased significantly with propofol (mean change from baseline to procedural
      termination -1.24 mm, standard error [SE] 0.25 and -0.79 mm, SE 0.13,
      respectively; P<=0.001 for both). Mean constriction velocity decreased by 0.84
      mm/s between baseline and procedural termination (P=0.001). Pupillary latency
      increased significantly between baseline and induction (mean change 0.016
      seconds, SE 0.007; P=0.04) but was not significantly different at other time
      points. CONCLUSION: We speculate that DP may be a useful tool to monitor propofol
      sedation.

PMID- 29026359
TI  - Innovation and Education Through Simulation at Ochsner.

PMID- 29026358
TI  - Medicine in Society Health Project: Five Students' Journey to a Resource-Limited
      Clinic in the Haitian Countryside.
AB  - BACKGROUND: Five medical students traveled with 4 doctors and a medical
      photographer to Mayaya, La Victoire, Haiti, as part of a Medicine in Society
      rotation to provide medical care to the indigenous population. METHODS:
      Preparation for the trip involved special study in identifying microbes and using
      blood analysis equipment; work in a clinic for underserved people in the New
      Orleans, LA, area; background reading; Haitian dialect classes; and development
      of ideas for streamlining clinic operations. RESULTS: During the week in country,
      the healthcare team saw 472 patients and made more than 1,100 diagnoses. A
      shortage in almost all needed medications was one of the biggest challenges.
      CONCLUSION: Each aspect of the pretrip training was useful but did not prepare
      the students for the conditions in the poorest country in the Western Hemisphere.
      Overall, the clinic functioned smoothly, and each student had an important role
      to play each day. Medicine in Society-Haiti gave the medical students a
      completely new perspective on medicine as they experienced firsthand the ethical
      dilemma of resource scarcity.

PMID- 29026360
TI  - Effects of Tobacco on Health and Disease: Three Decades of the Alton Ochsner
      Award.

PMID- 29026362
TI  - Inflammatory Myofibroblastic Tumor of the Breast Mimicking Malignancy in an
      Elderly Male.
AB  - BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare, distinctive
      lesion composed of a proliferation of myofibroblastic spindle cells accompanied
      by an inflammatory infiltrate. It was first described in the lung, but its
      occurrence at various extrapulmonary sites has also been reported. The literature
      mentions only a handful of cases of IMT in the breast and only 1 case in the male
      breast. We report the second case of IMT in the male breast. CASE REPORT: A 60
      year-old male presented with a large, lobulated lump in the left breast that had
      progressively increased in size during the past year. The lump measured 15 * 10
      cm. Ultrasonography revealed a solid mass lesion with regular borders in the
      subcutaneous plane of the left anterior chest wall. Fine-needle aspiration
      cytology showed a cellular mesenchymal tumor. Macroscopically, the nodule was
      firm, circumscribed, and yellow. On microscopic examination, the tumor was
      composed of bland spindle cells arranged in sheets and short fascicles along with
      a rich inflammatory infiltrate comprising predominantly plasma cells, admixed
      with lymphocytes, neutrophils, and eosinophils. On immunohistochemistry, the
      tumor cells were positive for vimentin, focally positive for smooth muscle
      antigen, and negative for anaplastic lymphoma kinase, CD34, S100, beta-catenin,
      and cytokeratin. Thus, a final diagnosis of IMT was rendered. CONCLUSION: IMT is
      a rare entity with intermediate clinical behavior. Knowledge of this entity and
      its recurrence and metastatic potential is of paramount significance to guide
      appropriate treatment and follow-up.

PMID- 29026361
TI  - Improving Patient Safety Communication in Residency Programs by Incorporating
      Patient Safety Discussions Into Rounds.
AB  - BACKGROUND: Engaging residents in patient safety and quality improvement
      initiatives is sometimes difficult. The primary goal of the current study was to
      develop a standardized learning experience designed to facilitate patient safety
      discussions during rounds. METHODS: Residents who were on inpatient rotations
      during a 2-month period in 2014 were exposed to patient safety discussions on
      rounds. Residents who were not on inpatient rotations served as a control group.
      Faculty received weekly text reminders with 3 questions designed to engage
      residents in patient safety discussions. Before and after the intervention,
      residents were asked to complete a modified Agency for Healthcare Research and
      Quality Hospital Survey on Patient Safety Culture. Faculty members were asked to
      complete a brief survey designed by the study investigators. RESULTS: Of the 160
      residents who participated in the study, 49 responded to both the preintervention
      and postintervention surveys (31%). Residents who participated in patient safety
      discussions during rounds reported higher frequencies of safety events reported
      compared to the control group (P<0.05). Both groups of residents reported better
      communication (P<0.01) and an increased number of safety events reported (P<0.01)
      at the end of the intervention. Twenty-two faculty were surveyed, and 19
      responded (86%). Most faculty felt incorporating patient safety discussions on
      rounds was constructive and that the residents were responsive. Few faculty
      members felt the patient safety discussions were burdensome. CONCLUSION: Using
      weekly text reminders with 3 prompts to incorporate patient safety discussions
      into rounds was well received by faculty and residents and had an impact on
      communication and error reporting.

PMID- 29026363
TI  - Highly Accelerated Onset of Hydroxychloroquine Macular Retinopathy.
AB  - BACKGROUND: Hydroxychloroquine (HCQ, Plaquenil) is often prescribed in lieu of
      other sulfate antimalarials to treat rheumatologic diseases because of its
      pharmacologic efficacy and few reported side effects. However, a known potential
      side effect of HCQ is retinal toxicity. CASE REPORT: A 61-year-old black female
      presented for screening of ophthalmic disease 2 months after initiation of HCQ
      for the treatment of polyarthralgia with a positive rheumatoid factor. At the
      time of the examination, she had taken a cumulative total of 19.8 g of HCQ and
      was found to have bilateral bull's-eye retinopathy. The patient had no known risk
      factors for HCQ toxicity. HCQ was discontinued, and the patient was prescribed
      ibuprofen for her polyarthralgia symptoms. The ophthalmic effects of HCQ toxicity
      were permanent. CONCLUSION: Known major risk factors for HCQ retinal toxicity
      include drug loads >300 mg/day (5 mg/kg/day), use for >5 years, a cumulative dose
      >1,000 g, underlying retinal disease or retinopathy, tamoxifen use, and renal
      disease. Despite not having any of these risk factors and having a reduced drug
      load during the treatment period, our patient developed the signs and symptoms of
      HCQ toxicity. This case suggests underlying mechanisms for HCQ toxicity other
      than those previously reported and a need for additional screening tests to
      prevent HCQ toxicity.

PMID- 29026364
TI  - Recurrent Pneumothoraces in a Patient With Pulmonary Benign Metastasizing
      Leiomyoma.
AB  - BACKGROUND: Pulmonary benign metastasizing leiomyoma (BML) is a rare disease with
      a malignant characteristic of spread from the uterus. Most cases are
      asymptomatic, and only 1% are associated with pneumothorax. CASE REPORT: We
      present the case of a 42-year-old female with recurrent pneumothoraces leading to
      an incidental finding of diffuse bilateral pulmonary nodules. The diagnosis of
      BML was based on the patient's history of uterine leiomyomata and confirmed by a
      biopsy showing benign smooth muscle staining for desmin and vimentin. CONCLUSION:
      BML should be considered in women with a history of leiomyomata who develop
      pneumothoraces resulting from peripheral pulmonary nodules. A standardized
      treatment regimen has yet to be established, and therapy plans require a
      multidisciplinary approach, involving gynecology, cardiothoracic surgery, and
      pulmonology.

PMID- 29026365
TI  - Incidental Finding of Bronchopulmonary Sequestration in a 64-Year-Old Female.
AB  - BACKGROUND: Bronchopulmonary sequestration is a congenital abnormality of the
      primitive foregut. In adults, the typical age at presentation is 20-25 years.
      CASE REPORT: A 64-year-old female was referred for evaluation of an 8 * 6-cm
      right lower lobe cystic lesion. Her medical history was significant for recurrent
      right lower lobe pneumonia requiring multiple hospitalizations. Her physical
      examination was significant for crackles at the right lung base. Computed
      tomography (CT) of the chest with contrast showed cystic changes with thickened
      septation of the medial segment of the right lower lobe lacking distinct visceral
      pleura and with arterial supply from the anomalous branch of the thoracic aorta
      arising near the celiac trunk. Pulmonary angiography confirmed the diagnosis of
      intralobar pulmonary sequestration. The patient underwent celiac endovascular
      coil embolization of the anomalous artery to lessen the risk of hemorrhage prior
      to video-assisted thoracoscopic surgery (VATS) resection of the right lower lobe.
      She recovered well and was discharged home 1 week after VATS lobectomy. Follow-up
      CT of the chest 2 months later showed normal postsurgical changes related to
      right lower lobe lobectomy. The patient remained asymptomatic and resumed her
      daily activities. CONCLUSION: Pulmonary sequestration can present with recurrent
      pneumonia in late adulthood. Physicians must review any previous imaging studies
      of the chest to identify the structural abnormality and be cognizant of
      differential diagnoses such as infected cystic bronchiectasis, bronchogenic cyst,
      congenital diaphragmatic hernia, or cystic adenomatoid malformation that can
      occur in conjunction with bronchopulmonary sequestration. Pulmonary angiogram is
      the gold standard to confirm the diagnosis of bronchopulmonary sequestration.
      Surgical resection is the standard of care.

PMID- 29026366
TI  - Trigeminal Trophic Syndrome Associated With the Use of Synthetic Marijuana.
AB  - BACKGROUND: Trigeminal trophic syndrome (TTS) is an uncommon disorder of the
      trigeminal nerve tract and trigeminal brainstem nucleus. The syndrome is
      characterized by a triad of unilateral crescentic ulcers with anesthesia and
      paresthesias of the involved trigeminal dermatomes. CASE REPORT: A 24-year-old
      right-handed black female presented to our emergency department with a 4-week
      history of rapidly progressive painless desquamation/denudation of skin over her
      right face and scalp. Four weeks prior, she had been admitted to another
      institution for seizures and was diagnosed with seizures provoked by synthetic
      marijuana use. She was afebrile during her initial presentation at our
      institution. Dermatologic examination revealed denudation of the epidermis and
      partial dermis over the right frontal, parietal, and temporal scalp with
      associated alopecia. CONCLUSION: To our knowledge, the association of disorders
      of the trigeminal nerve pathway, including TTS, with the use of synthetic
      marijuana has not been previously reported. The long-term neurologic effects of
      synthetic marijuana are difficult to predict, and the pathologic underpinnings of
      TTS are largely unknown. Further studies dedicated to exploring the underlying
      molecular and cellular mechanisms may translate into effective therapies and
      approaches to halt and reverse the process and prevent tissue destruction and
      cosmetic disfigurement.

PMID- 29026367
TI  - Mitochondrial Encephalomyopathy With Lactic Acidosis and Stroke-Like Episodes
      MELAS Syndrome.
AB  - BACKGROUND: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like
      episodes (MELAS) syndrome is a rare inherited disorder that results in waxing and
      waning nervous system and muscle dysfunction. MELAS syndrome may overlap with
      other neurologic disorders but shows distinctive imaging features. CASE REPORT:
      We present the case of a 28-year-old female with atypical stroke-like symptoms, a
      strong family history of stroke-like symptoms, and a relapsing-remitting course
      for several years. We discuss the imaging features distinctive to the case, the
      mechanism of the disease, typical presentation, imaging diagnosis, and disease
      management. CONCLUSION: This case is a classic example of the relapse-remitting
      MELAS syndrome progression with episodic clinical flares and fluctuating patterns
      of stroke-like lesions on imaging. MELAS is an important diagnostic consideration
      when neuroimaging reveals a pattern of disappearing and relapsing cortical brain
      lesions that may occur in different areas of the brain and are not necessarily
      limited to discrete vascular territories. Future studies should investigate
      disease mechanisms at the cellular level and the value of advanced magnetic
      resonance imaging techniques for a targeted approach to therapy.

PMID- 29026369
TI  - Corrigendum: Ethnopharmacological Approaches for Therapy of Jaundice: Part II.
      Highly Used Plant Species from Acanthaceae, Euphorbiaceae, Asteraceae,
      Combretaceae, and Fabaceae Families.
AB  - [This corrects the article on p. 519 in vol. 8, PMID: 28848436.].

PMID- 29026368
TI  - Serum protein pattern associated with organ damage and lupus nephritis in
      systemic lupus erythematosus revealed by PEA immunoassay.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is a remarkably heterogeneous
      autoimmune disease. Despite tremendous efforts, our knowledge of serum protein
      patterns in severe SLE phenotypes is still limited. We investigated the serum
      protein pattern of SLE, with special emphasis on irreversible organ damage and
      active lupus nephritis (LN) as assessed by renal Systemic Lupus Erythematosus
      Disease Activity Index. METHODS: We used proximity extension immunoassay (PEA,
      Proseek Multiplex, Olink) to assess the serum levels of ninety-two inflammation
      related proteins in Czech patients with SLE (n = 75) and age-matched healthy
      control subjects (n = 23). Subgroup analysis was carried out on the basis of
      organ damage (with/without, 42/33) and biopsy-proven LN (with/without, 27/48;
      active LN, n = 13; inactive LN, n = 14). RESULTS: Of thirty deregulated proteins
      between SLE and the healthy controls (Pcorr  < 0.05), the top upregulated
      proteins in SLE were sirtuin 2, interleukin 18 (IL18), and caspase 8 (Pcorr  <
      0.0006). Of these, sirtuin 2 and caspase 8 had not yet been reported with SLE.
      Elevated levels of IL8, CCL2/MCP1, CCL11, and MMP10 (Pcorr  < 0.05) were detected
      in patients with organ damage for which the serum levels of CCL11 and MMP10 were
      particularly informative in organ damage prediction. Comparing patients based on
      LN, elevated levels of CSF1, sIL15RA, sCD40, sCX3CL1, caspase 8, sIL18R1, bNGF,
      and GDNF (Pcorr  < 0.05) were detected in active LN. Except GDNF, all LN
      associated markers showed usefulness in prediction of active renal disease.
      CONCLUSIONS: This highly sensitive PEA analysis identified the serum pattern of
      SLE, organ damage, and active LN, with many novel candidate proteins detected.
      Their exact role and suitability as biomarkers in SLE deserve further
      investigation.

PMID- 29026370
TI  - Preliminary molecular characterization of a proinflammatory and nociceptive
      molecule from the Echinometra lucunter spines extracts.
AB  - BACKGROUND: Sea urchins are animals commonly found on the Brazilian shoreline,
      being Echinometra lucunter the most abundant species. Accidents caused by E.
      lucunter have been reported as one of the most frequent in Brazil, and are
      characterized by intense pain and inflammation, consequence of spine puncture in
      the skin. In order to characterize such toxic effects, we isolated one molecule
      that caused inflammatory and nociceptive effects. METHODS: E. lucunter specimens
      were collected without gender distinction. Spines were removed and molecules were
      extracted, fractionated by RP-HPLC and assayed for inflammatory and nociceptive
      activity, in a biological-driven fractionation way, until the obtainment of one
      active molecule and its subsequent analysis by mass spectrometry (MS and MS/MS).
      For inflammation, intravital microscopy was performed on the mouse cremaster
      muscle, in order to evaluate rolled, adherent and migrating leukocytes. Paw edema
      was also evaluated. For the nociceptive activity, the paw pressure test was
      performed in rats. RESULTS: One molecule could be isolated and related to the
      inflammatory and nociceptive activity. Regarding inflammation, increase in
      adherent and migrating cells was observed in the cremaster muscle after the
      administration of the molecule. Corroborating the inflammatory response, paw
      edema was also observed, although only in 20% of controls and 20 min after
      injection. Additionally, this molecule was able to decrease significantly the
      pain threshold, characterizing hyperalgesia. This molecule was analyzed by mass
      spectrometry, and according to the exact molecular mass, isotopic distribution
      and fragmentation profile, it was possible to propose the molecular formula
      C29H48N3O10. CONCLUSIONS: One isolated molecule from the spine extract of E.
      lucunter is able to elicit inflammation and hypernociception in animal models,
      which is in agreement with the effects observed in sea urchin accidents.

PMID- 29026371
TI  - Proportion and factors associated with low fifth minute Apgar score among
      singleton newborn babies in Gondar University referral hospital; North West
      Ethiopia.
AB  - BACK GROUND: New born babies with low Apgar scores are at an increased risk of
      perinatal morbidity and mortality. OBJECTIVE: To assess proportion and factors
      associated with low 5th minute Apgar Apgar score among singleton newborn babies
      in Gondar University referral hospital; North West Ethiopia. METHODS: A cross
      sectional study was conducted on singleton 261 live births from March - May,
      2013. Data was collected from mother/newborn index using a structured and pre
      tested questionnaire. It was then cleaned, coded and entered using EPI INFO
      version 3.4.3, then analyzed with IBM SPSS statistics versions 20.0. Logistic
      regression was used to identify significant variables with low 5th minute Apgar
      score. RESULT: The proportion of low 5th minute Apgar score in this study was
      13.8%. Factors that were significantly associated with low 5th minute Apgar score
      were: non-vertex fetal presentation, prolonged labor, presence of meconium
      stained liquor, induced/augmented labor and low birth weight. CONCLUSION: Mainly
      obstetric factors contribute to low Apgar score. Improving labor management
      through implementing regular use of partograph, 1:1 midwife-client ratio and
      advanced electronic fetal monitoring technology is recommended.

PMID- 29026372
TI  - Delivery practices, hygiene, birth attendance and neonatal infections in
      Karamoja, Uganda: a community-based study.
AB  - BACKGROUND: Drawing attention to home birth conditions and subsequent neonatal
      infections is a key starting point to reducing neonatal morbidity which are a
      main cause of mortality in sub-Saharan Africa. OBJECTIVES: To determine the
      proportion of respiratory, ophthalmic, and diarrhoeal infections in neonates; the
      proportion of mothers of neonates, following clean delivery practices; and to
      explore existing community practices during delivery and the neonatal period.
      METHODS: A descriptive, cross-sectional, exploratory study, including 10
      questionnaires and five Key-Informant interviews, in rural Karamoja, Uganda.
      RESULTS: Post-delivery razor blade and string use was 90%, but clean delivery
      surface use only 30%, while 90% obtained bathing water for neonates from
      boreholes. No mothers washed hands after latrine-related activities compared with
      83% for food-related activities. None delivered in health centres or with skilled
      birth attendants. Respiratory infections occurred in eight neonates, compared to
      two ophthalmic infections, and no diarrhoea. CONCLUSION: Use of clean delivery
      surfaces needs to be improved as well as washing after latrine-related
      activities. Diarrhoea was far less common than expected. Since rural Mother
      Infant pairs spend the majority of their post-delivery time around the homestead,
      hygiene impacts neonatal infections to a large degree, possibly even more so than
      delivery practices.

PMID- 29026373
TI  - How weight during pregnancy influences the association between pre-pregnancy body
      mass index and types of delivery and birth: a comparison of urban and rural
      areas.
AB  - BACKGROUND: Women in study areas suffered from the problems of caesarean delivery
      (CD), low birth weight (LBW), and macrosomia. OBJECTIVE: To investigate how
      gestational weight gain (GWG) influences the effect of the pre-pregnancy body
      mass index (BMI) on the risks of CD, LBW, and macrosomia in urban and rural areas
      in a city of Iran. METHODS: We used 767 and 612 eligible subjects from the public
      health care centers in urban and rural areas respectively. RESULTS: The risk of
      CD increased from 74% to 2.62-fold in urban and from 62% to 2.15-fold in rural
      areas, and the risk of macrosomia increased from 58% to 2.35-fold in urban and
      from 47% to 96% in rural areas, among obese women compared to normal weight women
      who gained above median GWG. The risk of LBW increased from 38% to 92% in urban
      and from 49% to 97% in rural areas among lean women compared to normal weight
      women who gained below median GWG. CONCLUSION: These findings strongly support
      the need to reform adequate pre-pregnancy weight and GWG against the risks of CD
      and macrosomia among overweight and obese women, and against the risk of LBW
      among lean women in both areas.

PMID- 29026375
TI  - Sexual risk behavior among HIV-positive persons in Jamaica.
AB  - BACKGROUND: HIV/AIDS remains a global public health challenge, especially in sub
      Saharan Africa and the Caribbean. Sexual risk behaviors among HIV-positive
      persons place their partners at risk for HIV transmission and other sexually
      transmitted infections. Stopping transmission acts among HIV-positive people is
      crucial in reversing HIV incidence. OBJECTIVE: This study aimed to assess the
      prevalence and predictors of sexual risk behaviors among HIV-positive individuals
      in clinical care in Northwestern Jamaica. METHODS: A cross-sectional survey of
      118 (33 males and 85 females) HIV-positive individuals was used to assess
      demographic and health characteristics, HIV/AIDS knowledge, attitudes, and
      beliefs and sexual risk behaviors. RESULTS: About 12% of the study population
      stated that they had unprotected anal or vaginal sex without disclosing their HIV
      status. Participants who agreed that condoms reduce the risk of HIV transmission
      were 13.1 times more likely to use condoms during their last sexual
      encounters(95% CI: 2.1-79.0) than those who disagreed. About 75% of participants
      reported using a condom every time they had sexual intercourse in the past year,
      while 25% used condoms irregularly. Participants who had unprotected anal or
      vaginal sex without disclosing their status were less likely to have used condoms
      during the last sexual encounter (OR=0.1; 95% CI: 0.02-0.5). CONCLUSION: The
      prevalence of unsafe sex remains high among sexually active people living with
      HIV/AIDS in Jamaica. Study participants who engaged in unprotected sex without
      disclosing their HIV-positive status potentially place their partners at risk for
      HIV transmission and other sexually transmitted infections. The study findings
      highlight the need to promote safe sexual behaviors and a positive social
      environment for people living with HIV/AIDS in Jamaica.

PMID- 29026376
TI  - Diversities in timing of sexual debut among Nigerian youths aged 15-24 years:
      parametric and non-parametric survival analysis approach.
AB  - OBJECTIVE: This study examined gender, generational, cultural and social
      diversities in timing of sexual debut among Nigerian youths and determined
      factors influencing the timings. METHODS: We extracted data of respondents aged
      15-24 years from 2012 Nigeria nationally representative data. The outcome of
      interest was time at sexual debut while predictors included residence, marital
      status, zones, education, religion, age at first marriage. Data was censored, cox
      proportional hazard and generalized gamma models were used to model age at sexual
      debut with p=0.05. RESULTS: The median survival time of sexual debut was 19
      years, female youths were twice as likely to begin sexual activities than their
      male counterparts, HR=1.99, 1.87-2.11 while uneducated youths were more than
      twice likely to have earlier sexual debut than those with higher education,
      HR=2.19, 1.95-2.25. Likelihood of having had sexual debut was about 30% higher
      among those aged 20-24 years than those aged 15-19 years, HR=1.27, 1.19-1.36.
      CONCLUSION: Females from poor households mostly in rural areas with no education
      and who married early in life were more likely to have earlier sexual debut. Both
      teenagers and young adults are on different trajectories of sexual debut but both
      urgently need sexual and reproductive health education to delay sexual debut.

PMID- 29026374
TI  - Geophagy as risk behaviour for gastrointestinal nematode infections among
      pregnant women attending antenatal clinics in a humid tropical zone of Nigeria.
AB  - BACKGROUND: Geophagy is wide spread among pregnant women in Ebonyi State,
      Nigeria. OBJECTIVE: The aim of this study was to assess intestinal nematode
      infections among geophagous pregnant women in Southern Ebonyi State, Nigeria.
      METHODS: Pregnant women were aged 17-45 years at gestational ages of >= 14 to 24
      weeks on hospital enrolment were sampled. Data on geophagy was collected using
      structured questionnaire. Gastrointestinal nematode status of the participants
      was determined by stool analyses. Soil types ingested were examined for
      intestinal nematode ova / larvae. RESULTS: The prevalence of geophagy (46.4%) was
      associated with socio-demographic characteristics. Ascaris lumbricoides and
      hookworm were associated with geophagy while Trichuris trichiura and
      Strongyloides stercoralis had no association. Prevalence of A. lumbricoides, T.
      trichiura and S. stercoralis differed significantly (p<0.05) between geophagous
      and non-geophagous women. The soil types consumed had eggs / larvae of A.
      lumbricoides and T. trichiura. Geophagy is a risk behaviour directly associated
      with A. lumbricoides, hookworm, T. trichiura, and to a lesser extent S.
      stercoralis infection among pregnant women. CONCLUSION: Sensitization and mass
      education of pregnant women on the dangers of geophagy is needed. Furthermore,
      deworming of pregnant women should be integrated into the healthcare delivery
      system of the State.

PMID- 29026377
TI  - Developmental screening: predictors of follow-up adherence in primary health
      care.
AB  - BACKGROUND: The importance of early identification for infants and young children
      with developmental delays is well established. Poor follow-up on referrals,
      however, undermines the effectiveness of early intervention programmes.
      OBJECTIVES: To identify factors, including text message reminders, that influence
      follow-up adherence for early intervention after developmental screening in
      primary health care. A secondary objective surveyed reasons for follow-up
      default. METHODS: The PEDS tools were used to screen 247 high-risk children. A
      risk assessment questionnaire was completed with caregivers whose children were
      referred for speech-language and/or occupational therapy (n=106, 43%). A quasi
      experimental correlational study was employed to identify risk factors for
      defaulting on appointments. A thematic analysis of telephonic interviews was also
      employed to determine reasons for follow-up defaults. RESULTS: Follow-up
      adherence was 17%. Participants who were never married, divorced or widowed were
      2.88 times more likely to attend a follow-up appointment than those who were
      married or living together (95%, CI 0.97-8.63). Text message reminders did not
      improve follow-up. More than half (58%) of participants who defaulted on
      appontments could be reached for telephonic interviews. Interviews showed that
      87% of participants were unconcerned about their child's development. Other
      reasons for defaulting were employment, logistical issues, other responsibilities
      and forgetfulness. CONCLUSION: Follow-up adherence for early intervention
      services following a positive primary health care screen was poor. Increased
      awareness and education regarding the importance of development for educational
      success is needed.

PMID- 29026378
TI  - Contextual determinants of adolescent mortality in South Africa.
AB  - OBJECTIVES: South Africa has a large adolescent population (approximately 20% of
      the total population). The survival and development of these individuals are a
      priority among parents and the government. In an effort to better understand the
      factors contributing to adolescent mortality in South Africa, this study examined
      the effect of household and community factors on adolescent death. METHODS: The
      study used data from Census 2001. Multilevel modelling was used to study the
      impact of community and household factors on adolescent mortality. A multivariate
      binary logistic 2-level model was developed. Odds ratios were produced and,
      statistically significant values (p<0.05) were discussed. There were 41,261
      reported adolescent deaths from census data. RESULTS: This study found that
      having a few household assets, six or more people living in a residence, and high
      racial diversity is associated with increased odds of adolescent mortality in
      South Africa in 2001. CONCLUSIONS: Socio-economic status of the household and
      racial diversity within communities is likely to increase adolescent mortality in
      South Africa. However, there is need to examine the role of other community
      characteristics, such as number of schools, health facilities and employment
      opportunities in order to create a holistic profile of the contextual
      determinants of adolescent mortality in the country.

PMID- 29026379
TI  - Distribution of symptoms of post-stroke depression in relation to some
      characteristics of the vulnerable patients in socio-cultural context.
AB  - OBJECTIVE: To determine the distribution of symptoms of post-stroke depression
      (PSD) in relation to some predisposing factors in an African population.
      RELEVANCE: Environment is a key determinant of behavior, and varied socio
      cultural contexts must have implications for modifiable characteristics (age,
      duration of the stroke, marital status, type of employment, gender, the location
      of cerebral lesion and complications) of individuals vulnerable to PSD, which may
      be targeted to enhance recovery. METHOD: This was a cross-sectional observational
      study of 50 (22 females and 28 males) stroke survivors (mean age=54.76+/-8.79
      years), at the physiotherapy department, the University of Nigeria teaching
      hospital, Enugu, selected using convenience sampling technique. Data were
      collected using Becks Depression Inventory and analyzed using Z-score, Chi-square
      test and univariate logistic regression, at p<0.05. RESULTS: PSD was more
      prevalent in females (45.45%); young(100%); middle-age(60%) adults(27-36/47-56
      years respectively); living with spouse (45%); left cerebral lesions (40.74%);
      complications(45%); cold case >3 years(47.05%); self-employed and unemployed
      (66.67%), respectively. Age was significantly associated with depression (chi2
      =4.92,df=1,p=0.03), and was related to the risk of PSD (3.7[1.1-12.0], p=0.03,
      phi +0.31, phi2=0.1). CONCLUSION: Age could be a risk factor for PSD, which was
      more prevalent in the elderly than young/middle-age adults, female gender, left
      cerebral lesion, complications, cold case; those living with a spouse, self
      employed and unemployed.

PMID- 29026380
TI  - Utilization of physiotherapy in the continuum of stroke care at a tertiary
      hospital in Ibadan, Nigeria.
AB  - OBJECTIVES: To investigate the pattern of referral for and utilisation of
      physiotherapy in the continuum of stroke care at a tertiary hospital in Ibadan,
      Nigeria. METHODS: Referral notes and medical records of patients admitted in the
      University College Hospital, Ibadan with a clinical diagnosis of stroke between
      January, 2009 and December, 2013 were retrospectively reviewed. Information on
      age, sex, type of stroke, length of hospital stay, referral for physiotherapy and
      utilisation of physiotherapy were retrieved. Data were summarised using
      descriptive statistics and analysed using Chi-square test. RESULTS: A total of
      783 patients with stroke were admitted in the hospital during the period under
      study. The in-patient mortality rate was 37.2%. The mean Length of Hospital Stay
      (LoHS) was 16.17+/-12.34 days. Referral rate for physiotherapy was high (75.8%)
      and the mean time from admission to referral for physiotherapy was three days.
      Majority of patients referred utilised physiotherapy (63.4%) and mean number of
      physiotherapy sessions received during in-patient care was 8.69+/-6.45. There was
      a significant association between LoHS and utilisation of in-patientphysiotherapy
      (p=0.02). CONCLUSION: The referral rate of stroke patients for physiotherapy was
      relatively high. Utilisation of in-patient physiotherapy reduced length of
      hospital stay among patients with stroke. Utilisation of out-patient
      physiotherapy was low. Strategies to enhance out-patient utilisation should be
      explored.

PMID- 29026381
TI  - A cross-sectional analysis of the association between age and gender and
      prescribed minimum benefit chronic disease list conditions among South Africans
      with concomitant hypertension, diabetes and dyslipidaemia.
AB  - BACKGROUND: Prescribed Minimum Benefit Chronic Disease List (PMB CDL) conditions
      are a regulated list of conditions most common to South Africa. OBJECTIVES: To
      investigate the prevalence and association between PMB CDL conditions and age and
      gender among patients with concomitant hypertension, diabetes and dyslipidaemia.
      METHODS: The study population consisted of patients (n = 17 866) with a
      prescription containing at least one co-prescribed antilipemics, antihypertensive
      and antidiabetic (identified using the MIMS Desk Reference). ICD-10 codes on
      claims for PMB CDL conditions were counted. RESULTS: 39.5% of patients had a PMB
      CDL condition. Women had higher odds for hypothyroidism (OR 6.30, 95% CI; 5.52,
      7.19, p < 0.001) and lower odds for coronary artery disease (CAD) (OR 0.63, 95%
      CI; 0.55, 0.72, p < 0.001) than men. In combination with hypothyroidism the odds
      for CAD were reversed and strongly increased; 3.54 (95% CI; 2.38, 5.25, p <
      0.001). The odds for females having cardiac failure (CF) was insignificant and
      low (OR 0.87, 95% CI; 0.75, 1.01, p = 0.063); however combined with
      hypothyroidism, the odds increased to 5.35 (95% CI; 3.52, 8.13, p < 0.001).
      CONCLUSION: Hypothyroidism was an important discriminating factor for co
      morbidity in women with concomitant hypertension, diabetes and dyslipidaemia, in
      particular with cardiovascular disease.

PMID- 29026382
TI  - Role of plasma adiponectin /C-reactive protein ratio in obesity and type 2
      diabetes among African Americans.
AB  - BACKGROUND: Obesity is a modifiable risk factor for hypertension and T2D.
      Objective(s): We examined relations between fasting plasma adiponectin (ADIP), C
      reactive protein (CRP) concentrations and markers of T2D in African Americans
      (AA). METHODS: Fasting plasma ADIP, CRP, Insulin (IN), HOMA-IR, lipid profiles,
      body fat percent (%BF), waist circumference (WC), body mass index (BMI) and blood
      pressure measures were determined in AA women (W: n=77) and men (M: n=34).
      Participants were classified into: 1) Normal fasting glucose (FG) and Normal %BF;
      2) Normal FG and High %BF; and 3) High FG. RESULTS: Compared to men, women had
      significantly higher mean ADIP (W: 31.4+/-2.9 vs. M: 18.0+/-4.4 ng/L), CRP (W:
      3.2+/-0.3 vs. M: 2.0+/-0.5 mg/L), %BF (W: 41.2+/-0.9 vs. M: 27.2+/-1.3), and BMI
      (W: 32.3+/-0.7 vs. M: 29.2+/-1.1 kg/m2). Women with normal FG and %BF had
      significantly higher ADIP (64.0+/-6.0) and lower CRP (1.3+/-0.6) concentrations
      than normal FG/ high %BF (ADIP: 37.0+/-5.0 and CRP: 3.1 +/-0.5) and high FG
      (ADIP: 15.1+/-4.1 and CRP: 4.0 +/- 0.5) groups. Women with high ADIP to CRP ratio
      had favorable metabolic and anthropometric profiles. CONCLUSION: Low ADIP and
      high CRP are associated with excessive %BF and FG in AA women. ADIP/CRP, may be
      useful for detecting metabolic dysregulation.

PMID- 29026383
TI  - Association between ALDH2 Glu504Lys polymorphism and colorectal cancer risk: a
      meta-analysis.
AB  - BACKGROUND: The findings from studies on the relationship between aldehyde
      dehydrogenases(ALDH) gene Glu504Lys polymorphism and colorectal cancer(CRC) were
      inconsistent. OBJECTIVES: The aim of this meta-analysis was to assess ALDH gene
      Glu504Lys polymorphism and CRC risk. METHODS: All of the relevant studies were
      identified from PubMed and Embase database. Statistical analyses were conducted
      with STATA 12.0 software. Odds ratio (OR) with 95% confidence interval (CI)
      values were applied to evaluate the strength of the association. Nine studies
      with 2779 cases and 4533 controls were included. RESULTS: No significant
      variation in CRC risk was detected in any of the genetic models overall. To
      explore the sources of heterogeneity,we performed further sub-group analyses by
      ethnicity and quality assessment of these studies. In the sub-group analysis by
      race, significant associations between ALDH gene Glu504Lys polymorphism and CRC
      risk were found in China(Glu/Lys vs Glu/Glu: OR = 0.70, 95%CI = 0.57-0.85; the
      dominant model: OR =0.69, 95%CI =0.48-0.98) and Japan(Lys/Lys vs Glu/Glu:OR
      =0.72, 95%CI =0.55-0.95). CONCLUSION: This meta-analysis suggests that the ALDH2
      Glu504Lys polymorphism may be associated with susceptibility to CRC. Furthermore,
      large and well-designed studies are needed to confirm these conclusions.

PMID- 29026384
TI  - Clinical and cranial computed tomography scan findings in adults following road
      traffic accidents in Kampala, Uganda.
AB  - BACKGROUND: Globally, road traffic accidents are a major cause of death and
      disability. The developing countries bear a disproportionately large share of the
      RTAs which account for about 85% of the deaths. Most of these RTAs result in head
      injury, which globally, most scholars and medical practitioners consider a
      significant economic, social and medical problem. In Mulago National referral
      hospital, RTA is the leading cause of surgical admission. OBJECTIVE: To describe
      the cranial computed tomography (CT) scan findings in adults following RTA in
      Mulago hospital. METHODS: Using CT, detailed analysis of 178 adult patients with
      head injury following RTA was performed. Data was analyzed using SPSS version 16
      and presented in tables and graphs. Data recorded included socio-demographic
      characteristics, clinical and CT variables. RESULTS: Seventy seven percent of the
      respondents were between 18-39 years. 52.6% of patients had open head injury.
      Headache was the most common clinical variable followed by dizziness and aphasia.
      The most common CT characteristic was extra cerebral haemorrhage followed by
      brain oedema and raised Intra-cranial pressure (ICP). Intra-cerebral haemorrhage
      was commonest in the frontal lobe followed by parietal lobe. CONCLUSION: Public
      health interventions like advocacy and education of the population on safe and
      responsible road usage should be emphasized to reduce on RTAs.

PMID- 29026385
TI  - A randomized controlled trial to assess the effect of a ketamine infusion on
      tourniquet hypertension during general anaesthesia in patients undergoing upper
      and lower limb surgery.
AB  - BACKGROUND: Tourniquet hypertension arising from tourniquet inflation remains a
      primary concern to the anaesthetist. One drug commonly used to manage tourniquet
      hypertension is ketamine. No studies have examined the effect of ketamine on
      tourniquet hypertension for a period of more than one hour or an infusion of the
      same. OBJECTIVE: To compare the effect of an intravenous infusion of ketamine
      versus placebo on tourniquet induced hypertension in patients undergoing upper
      and lower limb surgery under general anaesthesia. METHODS: Forty six adult
      patients scheduled for upper and lower limb surgery under general anaesthesia
      were randomized into two equal groups. The ketamine group received an intravenous
      bolus of 0.1mg/kg of ketamine followed by an infusion of 2ug/kg/min. The saline
      group received an intravenous bolus of physiological saline followed by an
      infusion of saline. All the patients were reviewed post-operatively. Data of the
      baseline characteristics, haemodynamic changes, post-tourniquet pain and side
      effects were collected. If post-tourniquet pain was present post-operatively, a
      visual analogue scale (VAS) was used to assess its severity. RESULTS: 46 patients
      successfully completed the trial. There were no significant differences between
      the groups for baseline patient demographics. The incidence of tourniquet
      hypertension was higher in the saline group (26.1%) compared with ketamine group
      (4.6%) with a 95% confidence interval. The difference was shown to be
      statistically significant ('P'<0.05). There was an increase in systolic blood
      pressure after 60 minutes of tourniquet inflation in the saline group but the
      difference was not statistically significant('P'>0.866). There were no
      significant differences between the groups as regards diastolic blood pressure
      and heart rate. VAS scores did not differ between the two groups. Statistically,
      there was no difference found between the two groups. Side effects were minimal
      in the ketamine group whilst in the saline group, nausea and vomiting were
      predominant but were also not statistically significant. CONCLUSION: Based on the
      results of this study, there was a difference in the proportion of tourniquet
      hypertension between the ketamine and saline groups for patients undergoing upper
      and lower limb orthopaedic surgery under general anaesthesia.

PMID- 29026386
TI  - Effect of posture on swallowing.
AB  - BACKGROUND: Swallowing is a systematic process. Any structural, physiological or
      neurological disturbance in this process may cause dysphagia. Although there are
      studies that report head/neck movements during mastication, there are fewer
      studies that show the effect of different head/neck postures on difficulty while
      swallowing. OBJECTIVES: To observe the effect of different body postures on the
      self-perceived difficulty while swallowing in normal healthy subjects. METHODS:
      Participants were asked to swallow 25 ml of water in one go while sitting
      upright, sitting with head/neck flexed, head/neck extended and lying supine.
      Following this, they had to rate their self-perceived difficulty while swallowing
      on a scale of 0-10, 0 being most easy and 10 being most difficult. RESULTS: 186
      subjects with mean age 32.7 SD 9.04 participated in this study. It was found to
      be least difficult to swallow when subjects were asked to swallow in upright
      sitting position. Statistically significant differences were found between
      sitting upright, sitting with head/neck flexed, head/neck extended and lying
      supine. CONCLUSION: Postural modification may help in rehabilitation of patients
      with dysphagia by affecting bolus flow to improve speed and safety of swallowing
      by closure of airways to prevent aspiration.

PMID- 29026387
TI  - The effect of a preanaesthesia clinic consultation on adult patient anxiety at a
      tertiary hospital in Kenya: a cohort study.
AB  - BACKGROUND: Preoperative anxiety is a common perioperative complication seen in
      approximately 11-80% of adults undergoing surgery. One of the goals of the
      preanaesthesia clinic is to allay anxiety. A preanaesthesia clinic evaluation has
      been shown to reduce anxiety however current studies on anxiety and the
      preanaesthesia clinic have not quantified this reduction. OBJECTIVE: To determine
      the reduction in anxiety in patients evaluated in the clinic versus those
      evaluated in the ward. METHODS: Fifty one adult patients with 28 patients in
      anaesthesia clinic (AC) group and 23 in the ward (W) group were sequentially
      recruited from both the surgical, gynaecology and antenatal outpatient clinics
      and the wards. The patient's State Trait Anxiety Index (STAI) was taken once the
      patient was booked for theatre. The patients then had a preanaesthesia evaluation
      either in the preanaesthesia outpatient clinic (PAC) or in the wards. Another
      STAI score was taken in the preoperative area in theatre on the day of surgery.
      The difference in the change of STAI scores in both groups was then analysed.
      RESULTS: Fifty one adult patients were recruited with 28 in the AC group and 23
      in the W group. The majority of patients were female (n=38). Statistically
      significant difference was seen in the reduction of the anxiety scores between
      the clinic group 2.143 (C.I=1.384-2.902) and ward group 0.74(C.I=0.17-1.31) with
      a p value=0.0051.There was also significant difference in reduction in anxiety
      scores within ward group in the patients with no prior anaesthetic experience
      having a greater reduction than those with prior anaesthetic experience. There
      were no other significant differences between the two groups. CONCLUSION:
      Patients evaluated in the anaesthesia clinic had a greater reduction in their
      anxiety but it was not as much as hypothesised which may be due to the multi
      factorial nature of preoperative anxiety. A larger multicenter study is
      recommended to increase generalizability to the population.

PMID- 29026388
TI  - Cytotoxicity testing of aqueous extract of bitter leaf (Vernonia amygdalina Del)
      and sniper 1000EC (2,3 dichlorovinyl dimethyl phosphate) using the Alium cepa
      test.
AB  - BACKGROUND: The unrefined nature of the herbal preparations from Vernonia
      amygdalina (VA) and toxicity potentials of Sniper may both have severe
      consequences on the biochemical and genetic systems. OBJECTIVES: To assess the
      microscopic and macroscopic effects of these substances. METHODS: VA leafs and
      Sniper were prepared and dissolved in distilled water to give different
      concentrations. Series of baseline tests were carried out to establish
      concentration range for root growth. Series of twelve onion bulbs of three per
      series was prepared, with a series of three onion bulbs serving as control.
      Chromosomal aberrations were statistically analysed using chi- squared test. Root
      bundle mean length was obtained after 96 hours and EC50 values at 95% confidence
      interval was determined from a plot of root length against sample concentrations
      using Microsoft Excel software. RESULTS: Total cytotoxic effect was induced by 2%
      sniper and 70% VA. EC50 for VA and sniper were 33.07 and 0.346 respectively. The
      two substances induced chromosomal aberrations and the effect was concentration
      dependent. CONCLUSION: There are risks of these widely used substances for
      therapeutic and environmental purposes.

PMID- 29026389
TI  - Oxidative stress and histopathological changes induced by methylthiophanate, a
      systemic fungicide, in blood, liver and kidney of adult rats.
AB  - BACKGROUND: Methyl-thiophanate (MT), a fungicide largely used in agriculture
      throughout the world including Tunisia, protects many vegetables, fruits and
      field crops against a wide spectrum of fungal diseases. Oxidative stress has been
      proposed as a possible mechanism involved in MT toxicity on non-target organism.
      METHODS: In the present study, the effect of MT injected intraperitoneally to
      adult rats at 300 or 500 mg/kg of body weight was studied on blood, liver and
      kidney. RESULTS: Our results showed 3 days after MT injection, a significant
      decrease in hemoglobin and hematocrit values. A disruption in total white blood
      cells and platelets also occurred. Accordingly, an increased in malondialdehyde,
      H2O2 and advanced oxidation protein levels in liver and kidney were noted with
      the two doses. A significant change in plasma biomarkers and organ enzymatic and
      non-enzymatic activities were observed after MT treatment. The modifications in
      biochemical parameters were substantiated by histopathological data. CONCLUSION:
      These data confirmed the pro-oxidant effects of this fungicide. Accordingly, care
      must be taken to avoid mammalian and human exposure to MT.

PMID- 29026390
TI  - Renal histoarchitectural changes in nevirapine therapy: possible role of
      kolaviron and vitamin C in an experimental animal model.
AB  - BACKGROUND: There is paucity of literature regarding the nephrotoxicity of
      antiretroviral drugs and its interaction with plant-based adjuvants. This study
      investigates the attenuating effect of kolaviron in nevirapine-therapy on the
      histological structure of the kidneys of adult male Sprague-Dawley rats.
      OBJECTIVE: To determine the attenuating influence of anti-oxidant status of
      kolaviron on the kidneys of experimental animals following nevirapine
      administration. METHODS: Forty eight pathogen-free adult male Sprague-Dawley rats
      were used for this study. The animals were divided into 8 groups (A-H) with 6
      animals in each group. Group A was given normal saline as the control; group B
      was given nevirapine; group C was given kolaviron; group D was given vitamin C;
      group E was given nevirapine and kolaviron; group F was given nevirapine and
      vitamin C; Group G was given nevirapine and kolaviron (kolaviron withdrawn after
      day 28) and group H was given corn oil. The experiment lasted 56 days after which
      the animals were sacrificed, blood samples were collected through cardiac
      puncture for serum analysis and the kidneys were harvested and prepared for H& E
      histological examination. RESULTS: Nevirapine caused histoarchitectural damage in
      the glomerular apparatus with resultant increase in kidney/body weight ratio
      (p<0.001). Adjuvant treatment with kolaviron attenuated these nephrotoxic
      effects. Serum anti-oxidant enzyme (SOD and CAT) activities were significantly
      reduced in kolaviron and vitamin C treated animals, whereas in the nevirapine
      group these parameters were significantly elevated (P<0.05). However, co
      administration of nevirapine and vitamin C did not improve the histoarchitecture
      of the kidney. CONCLUSION: Adjuvant treatment with kolaviron (an anti-oxidant)
      for 56 days appears to attenuate the nephrotoxicity of nevirapine in this model.

PMID- 29026391
TI  - Prevalence of khat chewing and its effect on academic performance in Sidama zone,
      Southern Ethiopia.
AB  - BACKGROUND: Khat use is a well-established public health problem in Yemen,
      Arabian Peninsula, and Ethiopia. Along with its large scale production, the
      magnitude of khat use is increasing among students. OBJECTIVE: This study was
      intended to assess the prevalence, determinants, and effect of khat use on
      academic performance of high school students in Sidama Ethiopia. METHODOLOGY: A
      cross-sectional study was conducted from April to June 2015. We used a stratified
      sampling technique to draw a total of 1,577 students. The data was collected
      using self-administered questionnaires and analyzed using SPSS version 20.
      Descriptive statistics and logistic regression models were used to determine the
      prevalence, effects, and predictors of khat use. RESULT: The life time and
      current prevalence of khat use were 14.6% and 13%, respectively. Smoking
      cigarette (AOR=5.1, 95% C.I: 2.3-14.3), drinking alcohol (AOR=3.0, 95% C.I: 1.4
      6.3), having a family growing khat (AOR=2.0, 95% C.I: 1.1-2.5), having friend
      chewing khat (AOR=3. 95% C.I: 2.0-4.6), were some of factors that increased the
      odds of students' khat use. Student's khat use increased the odds of student's
      poor academic performance (AOR=2.1, 95% C.I: 1.1-3.9). CONCLUSION: The prevalence
      of khat use in high khat producing districts of Sidama and its contribution to
      poor academic performance demand prompt intervention.

PMID- 29026392
TI  - Evaluation of the mobile phone electromagnetic radiation on serum iron parameters
      in rats.
AB  - BACKGROUND: Electromagnetic fields (EMF) created by mobile phones during
      communication have harmful effects on different organs. OBJECTIVES: It was aimed
      to investigate the effects of an EMF created by a mobile phone on serum iron
      level, ferritin, unsaturated iron binding capacity and total iron binding
      capacity within a rat experiment model. METHODS: A total of 32 male Wistar albino
      rats were randomly divided into the control, sham, mobile phone speech (2h/day)
      and stand by (12 h/day) groups. The speech and stand by groups were subjected to
      the EMF for a total of 10 weeks. RESULTS: No statistically significant difference
      was observed between the serum iron and ferritin values of the rats in the speech
      and stand by groups than the control and sham groups (p>0.05). The unsaturated
      iron binding capacity and total iron capacity values of the rats in the speech
      and stand by groups were significantly lower in comparison to the control group
      (p<0.01). CONCLUSION: It was found that exposure to EMF created by mobile phones
      affected unsaturated iron binding capacity and total iron binding capacity
      negatively.

PMID- 29026393
TI  - In vitro investigation of clofazimine analogues for antiplasmodial, cytotoxic and
      pro-oxidative activities.
AB  - BACKGROUND: Tetramethyl-piperidine-substituted, B4119 and B4158 have been shown
      to exhibit antiplasmodial activity. OBJECTIVES: The in vitro antiplasmodial,
      cytotoxic and oxidative activities of clofazimine and its analogues, all TMP
      (tetramethylpiperidyl)-substituted phenazines except B669, were evaluated in this
      study. METHODS: The antiplasmodial activity of the compounds against RB-1 and
      pfUP10 laboratory strains of Plasmodium falciparum was investigated by flow
      cytometry. The cytotoxic activity against HeLa cells and oxidative activity were
      studied employing colorimetric and cytochrome C reduction assays respectively.
      RESULTS: The riminophenazine agents exhibited antiplasmodial action of varying
      degrees: B669, B4100 and B4103 showed the best activity while B4121 and B4169
      exhibited significant activity at 2ug/ml. Clofazimine had no antiplasmodial
      activity. The compounds B4100, B4103, B4121 and B4169 exhibited significant
      cytotoxic activity against HeLa cells at concentrations of 0.5ug/ml and above
      while B669 was active at 2ug/ml. Clofazimine and B669 tested at a concentration
      of 0.5ug/ml caused enhancement (p <= 0.05) of neutrophil superoxide production
      when compared to the FMLP control while all the other TMP-derivatives had no
      effect (p >= 0.05). CONCLUSION: Tetramethylpiperidyl-subsituted phenazines may
      potentially be useful antimalarial/antitumor agents with no pro-oxidative
      properties. In vivo studies on the agents relative to these properties are
      recommended.

PMID- 29026394
TI  - Quorum sensing inhibitory activity of sub-inhibitory concentrations of beta
      lactams.
AB  - INTRODUCTION: The virulence factors of Pseudomonas aeruginosa are under the
      control of quorum sensing (QS) signals. Hence, interference with QS prevents its
      pathogenesis. OBJECTIVE: The aim of the present research is to assess the
      influence of some beta-lactam antibiotics on cell communication and the release
      of different virulence factors. METHODS: The minimal inhibitory concentrations of
      ceftazidime, cefepime and imipenem were evaluated by microbroth dilution method.
      The effect of sub-inhibitory concentration of the tested antibiotics on QS
      signals was investigated using reporter strain assay. In addition, different
      virulence factors (elastase, protease, pyocyanin and hemolysin) were estimated in
      the presence of their sub-inhibitory concentrations. RESULTS: Low concentrations
      of ceftazidime, cefepime and imipenem caused significant elimination of the QS
      signals 3OH-C12-HSL and C4-HSL up to 1/20 MIC. Furthermore, low concentrations of
      the tested antimicrobials suppressed virulence factors elastase and hemolysin.
      Moreover, 1/20 of their MICs reduced elastase, protease, pyocyanin and hemolysin.
      CONCLUSION: Utilization of beta-lactam antibiotics at low concentrations could be
      an effective approach for prevention and treatment of P. aeruginosa infection.

PMID- 29026395
TI  - Tuberculosis among HIV-infected population: incidence and risk factors in rural
      Tanzania.
AB  - BACKGROUND: The incidence of tuberculosis among HIV-infected populations with
      high CD4 count in high burden countries has not been well studied. OBJECTIVE: To
      assess the TB incidence in HIV-infected adults and its associated risk factors.
      METHOD: A cohort study with retrospective review of medical records and
      prospective follow-up of HIV-infected adult participants attending CTC who were
      18-55 years old, had CD4 count more than 250 cells/mm3 in the period of 2008-2010
      and were not on ART at enrolment. Cox proportional hazard regression was used to
      explore the predictors of incident TB. RESULTS: Overall 777 (24%) of 3,279 CTC
      enrolled HIV-infected adults fulfilled the inclusion criteria of the study. The
      incidence of TB in the study population ranged from 0.8/100 per person years (PY)
      at risk (95% CI 0.5-1.3) in the main analysis to 1.7/100 PY at risk (95% CI 1.0
      2.6) in sensitivity analyses. Only prior history of TB disease was found to have
      a significant association with an increased risk of TB, hazard ratio 5.7 (95% CI
      2.0-16.4, p value 0.001). CONCLUSION: Tuberculosis incidence among HIV-infected
      adults with medium/high CD4 count in Bagamoyo is lower than in other high TB
      burden countries. Previously TB treated patients have a much higher risk of
      getting TB again than those who never had TB before.

PMID- 29026396
TI  - Willingness by people living with HIV/AIDS to utilize HIV services provided by
      Village Health team workers in Kalungu district, central Uganda.
AB  - BACKGROUND: Less than one quarter of people in need have access to HIV services
      in Uganda. This study assessed willingness of people living with HIV/AIDS
      (PLWHAs) to utilize HIV services provided by Village Health Teams (VHTs) in
      Kalungu district, central Uganda. METHODS: A cross-sectional study conducted in
      two health facilities providing anti-retroviral therapy enrolled 312 PLWHAs. Pre
      tested semi-structured questionnaires were administered to participants at
      household level. A forward fitting logistic regression model computed the
      predictors of willingness of PLWHAs to utilize services provided by VHTs.
      RESULTS: Overall, 49% were willing to utilize HIV services provided by VHTs
      increasing to 75.6% if the VHT member was HIV positive. PLWHAs who resided in
      urban areas were more likely to utilize HIV services provided by VHTs (AOR 0.24,
      95%CI 0.06-0.87). Barriers to utilizing HIV services provided by VHTs were:
      income level > 40 USD (AOR 6.43 95%CI 1.19-34.68), being a business person (AOR
      8.71 95%CI 1.23-61.72), peasant (AOR 7.95 95%CI 1.37-46.19), lack of
      encouragement from: peers (AOR 6.33 95%CI 1.43-28.09), spouses (AOR 4.93 95%CI
      1.23-19.82) and community leader (AOR 9.67 95%CI 3.35-27.92). CONCLUSION: Social
      support could improve willingness by PLWHAs to utilize HIV services provided by
      VHTs for increased access to HIV services by PLWHA.

PMID- 29026397
TI  - Role of contact tracing in containing the 2014 Ebola outbreak: a review.
AB  - BACKGROUND: The 2014 outbreak of Ebola virus disease which emerged in the month
      of March in the year 2014 in Guinea has been declared as a public health
      emergency of international concern. OBJECTIVES: The objectives of the review
      article are to assess the role of contact tracing in the Ebola outbreak and to
      identify the challenges faced by the health workers while performing contact
      tracing. METHODS: An extensive search of all materials related to the Ebola
      outbreak and contact tracing was carried out in PubMed, Medline, World Health
      Organization website and Google Scholar search engines. Keywords used in the
      search included Ebola virus disease, West-Africa, contact tracing, World Health
      Organization. Overall 60 articles were selected and included in the discussion.
      RESULTS: Contact tracing is an important strategy in epidemiology and refers to
      the identification and diagnosis of those individuals who have come in contact
      with an infected person. It ultimately aims to reduce the time span required to
      detect and treat a case of an infectious disease and hence significantly minimize
      the risk of transmission to the subsequent susceptible individuals. In-fact,
      contact tracing continues to remain an important measure, as it aids the
      epidemiologist in containing the infection. CONCLUSION: The strategy of contact
      tracing has a great potential to significantly reduce the incidence of cases of
      Ebola virus disease. However, its success is eventually determined by the level
      of trust between the community and the public health system and the quality of
      the diagnostic & treatment services.

PMID- 29026398
TI  - Where there is no doctor: can volunteer community health workers in rural Uganda
      provide integrated community case management?
AB  - INTRODUCTION: Integrated community case management (iCCM) involves assessment and
      treatment of common childhood illnesses by community health workers (CHWs).
      Evaluation of a new Ugandan iCCM program is needed. OBJECTIVES: The objectives of
      this study were to assess if iCCM by lay volunteer CHWs is feasible and if iCCM
      would increase proportions of children treated for fever, pneumonia, and
      diarrhoea in rural Uganda. METHODS: This pre/post study used a quasi-experimental
      design and non-intervention comparison community. CHWs were selected, trained,
      and equipped to assess and treat children under five years with signs of the
      three illnesses. Evaluation included CHW-patient encounter record review plus
      analysis of pre/post household surveys. RESULTS: 196 iCCM-trained CHWs reported
      6,276 sick child assessments (45% fever, 46% pneumonia, 9% diarrhoea). 93% of
      cases were managed according to algorithm recommendations. Absolute proportions
      of children receiving treatment significantly increased post-intervention:
      antimalarial for fever (+24% intervention versus +4% control) and oral
      rehydration salts/zinc for diarrhoea (+14% intervention versus +1% control).
      CONCLUSION: In our limited-resource, rural Ugandan setting, iCCM involving lay
      CHWs was feasible and significantly increased the proportion of young children
      treated for malaria and diarrhoea.

PMID- 29026399
TI  - Healthcare spending and health outcomes: evidence from selected East African
      countries.
AB  - BACKGROUND: Over the last decade, total healthcare expenditures, comprised of
      both public and private healthcare expenditures, have increased in most East
      African countries. At the same time, health outcomes such as infant mortality
      rates, life expectancy at birth and other health outcome indicators have
      improved. OBJECTIVES: This paper examines the association between healthcare
      expenditures and health outcomes for eight East African countries: Burundi,
      Eritrea, Ethiopia, Kenya, Rwanda, Sudan, Tanzania, and Uganda. In this study,
      health outcomes are defined as an improvement in adult life expectancy and a
      reduction in the number of neonatal, infant, and under-five deaths. METHODS: We
      implemented a panel data regression technique, analyzing both cross-sectional and
      time series information. This combined method has been used in healthcare studies
      by several authors. Data obtained from world development indicators for the years
      2000-2014 was used for the panel study. RESULTS: First, we documented that there
      is a strong, positive association between total healthcare expenditures and total
      life expectancy. While we identified a positive relationship between healthcare
      expenditures and female and male life expectancy, we found that healthcare had a
      stronger effect on improving life expectancy in females than in males. Moreover,
      we found a negative relationship between healthcare expenditures and the number
      of neonatal, infant, and under-five deaths. CONCLUSION: The results of this study
      have important policy and management implications for the eight East African
      countries. From a policy perspective, it is necessary to understand if a greater
      allocation of resources to the healthcare sector is worthwhile and to determine
      whether to encourage private healthcare investment. From the management
      perspective, investing in more private institutions, such as hospitals and
      clinics, is essential for health outcomes in the average country. The results of
      this study can be used by the World Health Organization as well as other non
      governmental organizations that provide financial assistance to East African
      countries.

PMID- 29026400
TI  - Hydroxyurea therapy in adult Nigerian sickle cell disease: a monocentric survey
      on pattern of use, clinical effects and patient's compliance.
AB  - BACKGROUND: The clinical prospects of hydroxyurea therapy in the management of
      sickle cell disease (SCD) require evaluation in the Nigerian setting to develop
      indigenous guidelines. This survey examines the pattern of hydroxyurea therapy,
      its clinico-haematologic benefits and safety profile in Nigerian SCD subjects.
      METHODS: A cross sectional pilot survey was carried out among 60 adult SCD
      subjects over 3 months. Data on clinical phenotypes, relevant haematological
      parameters and details of hydroxyurea therapy were obtained using a structured
      questionnaire through an interview process and case file review. RESULTS: The
      median age was 30 years. Thirty-four (56.7%) of the subjects are aware of
      hydroxyurea therapy in SCD. Twenty-four (40%) SCD patients had previously used
      hydroxyurea. Only 4 subjects were fully compliant. Reasons for non-compliance
      included poor knowledge and lack of funds. In particular, hydroxyurea reduced
      leucocyte count and increased mean red cell volume (MCV) in compliant subjects.
      CONCLUSION: Hydroxyurea use is low among Nigerian SCD subjects despite its proven
      efficacy/clinical prospects in the developed nations. Large scale multicenter
      studies and clinical trials are needed to form a basis for developing standard
      local treatment protocol for its use.

PMID- 29026401
TI  - The sensitivity of Na+, K+ ATPase as an indicator of blood diseases.
AB  - BACKGROUND: Blood-related hereditary diseases are widespread in Eastern and
      SouthWestern regions of Saudi Arabia until recently. In this study, we used Na+,
      K+ATPase as an enzymatic indicator for the diagnosis of the diseases. MATERIALS
      AND METHODS: Individuals with different blood diseases (iron deficiency (n=13),
      anemia (n=14), thalassemia (n=16) and sickle cell anemia (n=12) were studied for
      Na+, K+-ATPase activity in the plasma membrane of red blood cell and compared
      with those of the healthy ones (n=20) of the same age and gender living in
      Jeddah, Saudi Arabia. RESULTS: There was a significant elevation in the specific
      activity of Na+, K+ATPase in individuals with anemia compared with those of
      control (0.0094 + 0.001 nmol / mg protein/min versus 0.0061 +/- 0.001). On the
      other hand, there was a significant reduction in enzyme activity in thalassemia
      (0.0028 +/- 0.002 nmol / mg protein/min) and sickle cell anemia cases (0.0042 +/
      0.001 nmol / mg protein/min) compared to the control group. The cut off value for
      Na+, K+ATPase activity is 0.005 umol Pi/min-showing 94% sensitivity and 93%
      specificity for the differentiation of blood abnormality. CONCLUSION: It can be
      recommended that the activity of Na+, K+-ATPase can be used for the diagnosis of
      individuals with blood diseases/disorders.

PMID- 29026402
TI  - Sonographic assessment of petroleum-induced hepatotoxicity in Nigerians: does
      biochemical assessment underestimate liver damage?
AB  - BACKGROUND: Exposure to petroleum products has been shown to have significant
      adverse effects on the liver which can manifest either as morphological or
      physiological changes. OBJECTIVES: The aim of the study was to assess the effects
      of chronic exposure to some petroleum products on the liver of exposed workers
      using sonography and to determine whether biochemical assessments underestimated
      hepatotoxicity. METHODS: Abdominal ultrasound was performed on 415 exposed
      workers in order to evaluate liver echogenicity and size. Also, biochemical
      assessment of the liver was done to evaluate its function. RESULTS: Statistically
      significant increase in the liver parenchymal echogenicity and the liver size was
      seen in the exposed workers compared with control (p <= 0.05). These increased as
      the exposure duration increased. It was also noted that out of 16.87% (N=70)
      exposed workers with abnormal liver echopattern, only 2.65% (N=11) had alanine
      aminotransferase above the reference range. CONCLUSION: The study revealed
      evidence of ultrasound detectable hepatotoxicity among the exposed subjects.
      Sonography appeared to detect petroleum products-induced hepatic toxicity more
      than biochemical assays suggesting that biochemical assessment may have
      underestimated toxicity.

PMID- 29026403
TI  - Practicalities of health survey fieldwork research in a resource limited setting:
      challenges and lessons learnt from Uganda.
AB  - BACKGROUND: Countless research has been undertaken in sub-Saharan African
      countries to provide evidence for health policy interventions. However, despite
      the bulk of health research, very few studies have documented the experiences and
      practicalities of conducting health survey fieldwork in such settings. METHODS:
      Results were obtained through synthesis of notes on fieldwork experiences
      documented during a household survey as part of a doctoral research project.
      Challenges faced and adaptive strategies developed to overcome or reduce the
      impact on the survey are highlighted. RESULTS: Key challenges included
      infrastructure and electrical power outages; sampling and access to clients;
      ethics approval and political stability; and safety and wellbeing of researchers.
      Adaptive strategies were developed to overcome the different challenges faced.
      CONCLUSION: The experiences highlighted and strategies developed to overcome
      fieldwork challenges give practical advice for future data collection research in
      similar sub-Saharan African settings.

PMID- 29026404
TI  - Investigation of the relationship between structural empowerment and
      organizational commitment of nurses in Zanjan hospitals.
AB  - BACKGROUND: The demanding nature of nursing work environments signals
      longstanding and growing concerns about nurses' health and job satisfaction and
      the provision of quality care. Specifically in health care settings, nurse
      leaders play an essential role in creating supportive work environments to avert
      these negative trends and increase nurse job satisfaction. OBJECTIVE: The purpose
      of this study was to examine the relationship between structural empowerment and
      organizational commitment of nurses. METHODS: 491 nurses working in Zanjan
      hospitals participated in this descriptive-correlational study in 2010. Tools for
      data collection were Meyer and Allen's organizational commitment questionnaire
      and "Conditions for Work Effectiveness Questionnaire-II" (CWEQ-II). Data was
      analyzed by SPSS16. The statistical tests such as variance analysis, t-test,
      pearson correlation coefficient and linear regression were used for data
      analysis. RESULTS: According to the findings, the perception of nurses working in
      hospitals on "Structural Empowerment" was moderate (15.98+/-3.29). Nurses
      believed "opportunity" as the most important element in structural empowerment
      with the score of 3.18 +/-0.79. Nurses working in non-academic hospitals and in
      non-teaching hospitals had higher organizational commitment than others. There
      was a significant relationship between structural empowerment and organizational
      commitment. CONCLUSION: Generally, structural empowerment (relatively strong)
      correlates with nurses' organizational commitment. We concluded that a high
      structural empowerment increases the organizational commitment of nurses.

PMID- 29026405
TI  - Lateral retroperitoneoscopic adrenalectomy for complicated adrenal tumor larger
      than 5 centimeters.
AB  - BACKGROUND: The role of lateral retroperitoneoscopic adrenalectomy (LRA) for
      complicated tumor with large diameter remains controversial, this study aimed to
      evaluate the effectiveness of this procedure on the management of tumor larger
      than 5cm in diameter. METHODS: A retrospective comparison was conducted of 67
      patients with large complicated adrenal tumor (>5cm). 41 patients received LRA,
      and 26 received open adrenalectomy (OA) in our hospital between January 2011 and
      June 2015. Basic characteristics regarding mean age, gender, body mass index
      (BMI), tumor size, tumor side, previous abdominal surgery, resection method,
      pathology were preferentially analyzed. Operative indicators regarding operation
      time, estimated blood loss (EBL), conversion to ICU, complications, post
      operative hospitalization, duration of drain, time to first oral intake and
      ambulation were compared between groups. RESULTS: There were no significant
      differences between the two groups in the basic characteristics. The mean
      operation time for LRA was shorter than OA (98.7+/-32.3 min vs 152.7+/-72.3 min,
      P = 0.001). EBL was 31.9+/-20.0 ml for LRA and 590.0+/-1181.1 ml for OA (P =
      0.03). There was no complication in LRA group and one patient in OA group had
      complications, but this difference was not significant (P = NS). The post
      operative hospitalization in LRA was 7.4+/-2.8 days, and shorter than 9.8+/-2.7
      days in OA group (P = 0.00). The time to first oral intake and ambulation for LRA
      was shorter than OA (first oral intake, 1.9+/-0.8 days vs 3.1+/-1.3 days, P =
      0.00; time to ambulation, 2.6+/-1.4 days vs 4.2+/-1.6 days, P = 0.00). While the
      difference between groups were not significant in terms of ICU conversion (3/41
      vs 4/26, P = NS) and duration of drain (3.9+/-2.2 days vs 4.7+/-1.9 days, P =
      NS). CONCLUSION: Our study shows that LRA can be performed safely and effectively
      for complicated adrenal tumors larger than 5 cm in diameter, but it remains
      technically demanding.

PMID- 29026407
TI  - Congenital hypothyroidism: insights into pathogenesis and treatment.
AB  - Congenital hypothyroidism occurs in approximately 1 in 2000 newborns and can have
      devastating neurodevelopmental consequences if not detected and treated promptly.
      While newborn screening has virtually eradicated intellectual disability due to
      severe congenital hypothyroidism in the developed world, more stringent screening
      strategies have resulted in increased detection of mild congenital
      hypothyroidism. Recent studies provide conflicting evidence about the potential
      neurodevelopmental risks posed by mild congenital hypothyroidism, highlighting
      the need for additional research to further define what risks these patients face
      and whether they are likely to benefit from treatment. Moreover, while the
      apparent incidence of congenital hypothyroidism has increased in recent decades,
      the underlying cause remains obscure in most cases. However, ongoing research
      into genetic causes of congenital hypothyroidism continues to shed new light on
      the development and physiology of the hypothalamic-pituitary-thyroid axis. The
      identification of IGSF1 as a cause of central congenital hypothyroidism has
      uncovered potential new regulatory pathways in both pituitary thyrotropes and
      gonadotropes, while mounting evidence suggests that a significant proportion of
      primary congenital hypothyroidism may be caused by combinations of rare genetic
      variants in multiple genes involved in thyroid development and function. Much
      remains to be learned about the origins of this common disorder and about the
      optimal management of less severely-affected infants.

PMID- 29026408
TI  - Camel Milk Has Beneficial Effects on Diabetes Mellitus: A Systematic Review.
AB  - CONTEXT: Controlling diabetes, a worldwide metabolic disease, by effective
      alternative treatments is currently a topic of great interest. Camel milk is
      believed to be a suitable hypoglycemic agent in experimental animals and patients
      with diabetes. The current systematic review aimed at evaluating the effect of
      camel milk on diabetes. EVIDENCE ACQUISITION: A comprehensive search was dine in
      PubMed and Scopus for all clinical trials and animal studies documented up to
      2015, which focused on the effect of camel milk on diabetes markers. Studies
      which assessed the effects of camel milk, with no dose limit, on glucose
      parameters and lipid profiles in animals or humans with diabetes, were included.
      The quality of the included clinical trials was evaluated by the Delphi score
      checklist. RESULTS: The initial search yielded 73 articles. After screening
      abstracts and full texts, 22 articles were included consisting of 11 animal
      studies and 11 clinical trials, 8 of which focused on type 1 diabetes and the
      other three on type 2diabetes. All animal studies except for 1 showed significant
      reductions in at least 1 of the diabetes parameters such as blood glucose,
      insulin resistance, glycated hemoglobin, and lipid profile. In most of the
      clinical trials, the recommended dose of camel milk was 500 mL/day, which led to
      improvement of diabetes markers even after 3 months in patients with diabetes.
      CONCLUSIONS: Most of the studies in the current systematic review demonstrated
      the favorable effects of camel milk on diabetes mellitus by reducing blood sugar,
      decreasing insulin resistance and improving lipid profiles.

PMID- 29026410
TI  - The effect of reflexotherapy and massage therapy on vital signs and stress before
      coronary angiography: An open-label clinical trial.
AB  - BACKGROUND: Complementary medicine interventions are now successfully used to
      reduce stress as well as to stabilize hemodynamic indices within different
      procedures. The present study aimed to examine the effect of massage therapy and
      reflexotherapy on reducing stress in patients before coronary angiography.
      METHODS: In this open-label clinical trial, 75 consecutive patients who were
      candidate for coronary angiography were randomly assigned to receive
      reflexotherapy (n = 25), or massage therapy (n = 25), or routine care (n = 25)
      before angiography. The Spielberger State-Trait Anxiety Inventory was used to
      determine the stress level of patients before and after interventions and vital
      signs were also measured. RESULTS: Improvement in diastolic blood pressure, heart
      rate, and respiratory rate was shown in the reflexotherapy group, and similar
      effects were observed following other interventions including massage therapy and
      routine resting program. In subjects who received reflexotherapy the level of
      stress decreased slightly compared with the other two groups. However, following
      interventions the level of stress in reflexotherapy group was shown to be lower
      than other study groups. CONCLUSION: Reflexotherapy before coronary angiography
      can help to stabilize vital sign as well as reduce the level of stress. The
      effect of massage therapy was limited to reducing stress.

PMID- 29026411
TI  - Healthy eating index and cardiovascular risk factors among Iranian elderly
      individuals.
AB  - BACKGROUND: Concurrent with increase in life expectancy, the prevalence of
      chronic diseases such as cardiovascular diseases (CVD) has also increased.
      Therefore, the aim of this study was to evaluate the association between healthy
      eating index (HEI) score and CVD risk factors among Iranian elderly. METHODS:
      This cross-sectional study was performed on a sample of elderly persons from
      Isfahan, Iran, in 2013. Totally, 107 retired subjects were entered in statistical
      analysis. A semi- quantitative food frequency questionnaire was used to assess
      the dietary intake of participants. Anthropometric measurements and blood
      pressure of participants were determined. Fasting blood samples were taken for
      biochemical assessments. RESULTS: The results of linear regression determined a
      significant inverse association between HEI score and homeostasis model
      assessment of insulin resistance [HOMA-IR, beta = -0.238 (-0.426, -0.048)],
      fasting blood glucose [beta = -0.194 (-0.383, -0.004)], and high-sensitivity C
      reactive protein [hs-CRP, beta = -0.196, (-0.386, -0.005)]. In addition, a
      significant positive association was observed between HEI score and high density
      lipoprotein cholesterol [HDL-C, beta = 0.196 (0.006, 0.385)] levels. However,
      after adjusting for confounding variables, these significant associations were
      disappeared except for hs-CRP [beta = -0.074 (-0.145, -0.003)]. CONCLUSION:
      Healthy eating index was associated with reduced risk of cardiovascular risk
      factors in old people. It seems that more adherence with healthy eating index
      could provide cardio-protective effects in elderly persons.

PMID- 29026412
TI  - The role of manual thrombectomy in cardiovascular outcome among patients with
      total cutoff vessel myocardial infarction undergoing primary percutaneous
      coronary intervention.
AB  - BACKGROUND: The applicability of manual aspiration thrombectomy in patients with
      ST-segment elevation myocardial infarction (STEMI) has been a challenging issue.
      This study aimed to compare the impact of additive manual thrombectomy on
      patients with myocardial infarction (MI) and total cutoff vessel with standard
      primary percutaneous coronary intervention (PPCI) with bailout thrombectomy.
      METHODS: In this case-control study, 181 patients with acute STEMI were enrolled
      who referred to Chamran Hospital (Isfahan, Iran) between August to December 2014.
      The culprit lesion was treated with routine PPCI with bailout thrombectomy (111
      patients) and routine primary thrombectomy then percutaneous coronary
      intervention [(PCI), 70 patients] during hospitalization and one month after
      discharge. Patients in the case group received manual thrombectomy before PPCI
      and patients in the control group received standard PPCI with bailout
      thrombectomy. Patients were followed during the study procedure, post
      hospitalization and one month later for cardiovascular outcomes including death,
      recurrent MI, stroke, major bleeding, post PCI arrhythmia, no reflow,
      thrombolysis in myocardial infarction (TIMI)-flow and TIMI myocardial blush grade
      (TMBG), which were assessed and recorded. RESULTS: Myocardial perfusion and
      angiographic outcomes had no significant differences in the two groups (P =
      0.730). There was also no significant difference in no reflow prevalence between
      the two groups (P > 0.990). There were no significant differences for primary
      outcomes such as death, stroke, major bleeding and arrhythmia between the two
      groups (P < 0.050). In particular, outcomes were the same for both groups during
      hospitalization period and one month after discharge. Mortality rate during
      hospitalization was 5.7% for the control group and 4.5% for the case group (P =
      0.730). However, one-month mortality rate was quite similar in both groups.
      CONCLUSION: This study showed there is no significant difference in
      cardiovascular outcomes such as death, stroke, bleeding, arrhythmia, target
      vessel revascularization, and distal embolization during hospitalization and one
      month after discharge in patients with acute MI and total cutoff of the involved
      vessel, who underwent PPCI with and without primary Export(r) aspiration catheter
      direct thrombosuction.

PMID- 29026409
TI  - Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders.
AB  - CONTEXT: There are contradictory results on the effect of hypothyroidism on the
      changes in hemostasis. Inadequate population-based studies limited their clinical
      implications, mainly on the risk of venous thromboembolism (VTE). This paper
      reviews the studies on laboratory and population-based findings regarding
      hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid
      disorders. EVIDENCE ACQUISITION: A comprehensive literature search was conducted
      employing MEDLINE database. The following words were used for the search:
      Hypothyroidism; thyroiditis, autoimmune; blood coagulation factors; blood
      coagulation tests; hemostasis, blood coagulation disorders; thyroid hormones;
      myxedema; venous thromboembolism; fibrinolysis, receptors thyroid hormone. The
      papers that were related to hypothyroidism and autoimmune thyroid disorder and
      hemostasis are used in this review. RESULTS: Overt hypothyroidism is more
      associated with a hypocoagulable state. Decreased platelet count, aggregation and
      agglutination, von Willebrand factor antigen and activity, several coagulation
      factors such as factor VIII, IX, XI, VII, and plasminogen activator-1 are
      detected in overt hypothyrodism. Increased fibrinogen has been detected in
      subclinical hypothyroidism and autoimmune thyroid disease rendering a tendency
      towards a hypercoagulability state. Increased factor VII and its activity, and
      plasminogen activator inhibitor-1 are among several findings contributing to a
      prothrombotic state in subclinical hypothyroidism. CONCLUSIONS: Overt
      hypothyroidism is associated with a hypocoagulable state and subclinical
      hypothyroidism and autoimmune thyroid disorders may induce a prothrombotic state.
      However, there are contradictory findings for the abovementioned thyroid
      disorders. Prospective studies on the risk of VTE in various levels of
      hypofunctioning of the thyroid and autoimmune thyroid disorders are warranted.

PMID- 29026413
TI  - Evaluation of pentraxin-3 level and its related factors in patients undergoing
      primary percutaneous coronary intervention.
AB  - BACKGROUND: Inflammation has an important role in the development and progression
      of atherosclerosis, and acute phase proteins such as pentraxin-3 (PTX3) can be
      deployed in determining the prognosis of coronary artery disease (CAD). So the
      purpose of this paper was to evaluate the PTX3 level and its related factors in
      patients undergoing primary percutaneous coronary intervention (PCI). METHODS: In
      this cross-sectional study, the PTX3 levels were determined for 100 patients with
      ST-elevation myocardial infarction referred to the Modarres Hospital, Tehran,
      Iran. Checklist included demographic data [age, gender, history of myocardial
      infarction (MI)] and characteristics of heart disease (type of MI, culprit, and
      pre-dilation). PTX3 was measured for all patients before PCI. RESULTS: In this
      study, the mean age of the participants was 58.7 (11.4). Global registry of acute
      coronary events (GRACE) score was higher in the group with abnormal PTX3 levels
      (P = 0.008). The number of the involved vessels (P = 0.005), MI type (P = 0.05),
      and the need for PCI all had a significant relation with abnormal PTX3 levels.
      The increased levels of PTX3 received higher Killip class, lower ejection
      fraction, and higher GRACE score. The group with abnormal PTX3 had a significant
      difference in platelet counts (P = 0.018) in comparison with the group with
      normal level of PTX3. CONCLUSION: Currently, the biomarkers are highly important
      in the field of cardiovascular diseases. The diagnostic and prognostic importance
      of PTX3 as a new marker has been underscored in recent studies. Differentiating
      between high-risk patients with acute cardiac infarction and low-risk ones
      through their clinical signs is difficult.

PMID- 29026414
TI  - Acute myocardial infarction in very young adults: A clinical presentation, risk
      factors, hospital outcome index, and their angiographic characteristics in North
      India-AMIYA Study.
AB  - BACKGROUND: India is currently in the fourth stage of epidemiological transitions
      where cardiovascular disease is the leading cause of mortality and morbidity.
      Purpose of the present study was to assess the risk factors, clinical
      presentation, angiographic profile including severity, and in-hospital outcome of
      very young adults (aged <= 30 years) with first acute myocardial infarction
      (AMI). METHODS: Total of 1,116 consecutive patients with ST-segment elevation
      acute myocardial infarction (STEMI) were studied between March 2013 and February
      2015 at LPS Institute of Cardiology, Kanpur, Uttar Pradesh, India. RESULTS: Mean
      age of the patients was 26.3 years. Risk factors were smoking (78.5%), family
      history of premature coronary artery disease (CAD) (46.8%), obesity (39.1%),
      physical inactivity (38.7%) and stressful life events (29.6%). The most common
      symptom and presentation was chest pain and anterior wall myocardial infarction
      (AWMI) in 94.8% and 58.8%, respectively. About 80.6% of patients had obstructive
      CAD with single vessel disease (57.6%), double-vessel disease (12.9%) and left
      main involvement (3.2%). Left anterior descending (LAD) was commonest culprit
      artery (58.1%) followed by right coronary artery in 28.2%. In-hospital mortality
      was 2.8%. Percutaneous coronary intervention was performed in 71.6% of patients.
      Median number and length of stent were 1.18 and 28 +/- 16 mm, respectively.
      CONCLUSION: AMI in very young adult occurred most commonly in male. Smoking was
      the most common risk factor. AWMI owing to LAD artery involvement was the most
      common presentation. Mean time of presentation after symptom onset was 16.9
      hours. In contrast to western population, it is characterised by earlier onset,
      delayed presentation, more severity, diffuse disease, and more morbidity but with
      favourable in-hospital mortality.

PMID- 29026415
TI  - Two cases of parachute tricuspid valve confirmed by three-dimensional
      echocardiography.
AB  - BACKGROUND: Parachute tricuspid valve is a rare congenital malformations
      explained in the literature. In most cases, this malformation coexists with other
      congenital defects. The importance of this condition depends on its functional
      consequences. CASE REPORT: First case was a 52-year-old female patient presented
      with palpitation. She had a history of paroxysmal supraventricular tachycardia.
      Transthoracic echocardiography revealed large secundum type atrial septal defect
      and all the tricuspid valve leaflets appeared to be connected to a single
      calcified papillary muscle in right ventricle suggestive of parachute tricuspid
      valve. Echocardiography showed severe right ventricle and right atrial
      enlargement, and moderate to severe tricuspid regurgitation without significant
      tricuspid stenosis. Another case was a 30-year-old female patient referred for
      echocardiography prior to her breast cancer chemotherapy. Transthoracic
      echocardiography revealed a right ventricle with an unusual fusion of papillary
      muscles resulting in a single calcified head for the attachment of all tricuspid
      leaflets. These findings were suggestive of a parachute-like tricuspid valve.
      Other data were mild to moderate tricuspid regurgitation without any stenosis,
      and normal right ventricle size and function. In both cases, parachute tricuspid
      valve was confirmed by three dimensional echocardiograph. CONCLUSION: In our
      first case, parachute tricuspid valve was associated with atrial septal defect,
      although in the second case, no associated anomaly was detected, a condition not
      previously reported in the literature. In both cases, parachute tricuspid valve
      was not associated with tricuspid stenosis. Based on other published cases,
      parachute involvement of the tricuspid valve is less often reported than cases
      involving the mitral valve. Additionally, the associated consequences in
      tricuspid valve position such as tricuspid stenosis seem to be less significant
      than cases involving mitral valve. It is recommended that in patients with
      tricuspid valve involvement, parachute anomaly should be considered as a possible
      rare cause.

PMID- 29026416
TI  - Right ventricular thrombosis as a manifestation of Behcet's syndrome.
AB  - BACKGROUND: Behcet's disease (BD) is a rare condition with a classic triad of
      oral and genital ulceration and eye disease. Cardiovascular complication is a
      rare finding in BD. CASE REPORT: In this report, we present a seventeen years old
      patient with a history of fever for 20 days, who developed a clot in right
      ventricle (RV). Cardiac magnetic resonance imaging (MRI) and echocardiography
      demonstrated a thrombosis in RV and a thoracic multi detector computed
      tomographic image showed pulmonary thromboembolism (PTE) in patient. The patient
      was administered with methylprednisolone, cyclophosphamide and anticoagulant. A
      regular follow-up was carried out. Two months later, the RV clot had disappeared
      on transthoracic echocardiography (TTE). CONCLUSION: In BD, early cardiac MRI and
      echocardiography should be performed for the detection of cardiac involvement,
      and medical treatment is the first choice of treatment.

PMID- 29026417
TI  - Some facts about the Metabolic Syndrome in Iran.

PMID- 29026418
TI  - Heterozygosity analysis of polycystic kidney disease 1 gene microsatellite
      markers for linkage analysis of autosomal dominant polycystic kidney disease type
      1 in the Iranian population.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most
      common genetic cause of end-stage renal disease. Although imaging techniques are
      a means of accurate diagnosis when the cysts appear in the third or fourth
      decades of the patient's life, they are of little value for early diagnosis.
      Genetic tests are required for preimplantation genetic diagnosis, decision-making
      for kidney donation to an affected relative. Although mutation of the polycystic
      kidney disease (PKD1) gene is solely responsible for the most cases of ADPKD,
      direct genetic testing is limited by the large size of this gene and the presence
      of many mutations without hot spots. Therefore, indirect diagnosis with linkage
      analysis using informative microsatellite markers has been suggested. MATERIALS
      AND METHODS: In this study, we assessed the informativeness of the PKD1 gene
      markers D16S475, D16S291, and D16S3252 in Iranian population. Using specific
      primers, fluorescent polymerase chain reaction (PCR) was performed on genomic DNA
      extracted from fifty unrelated individuals. PCR products were analyzed by the
      ALFexpress DNA sequencer system, and the number and frequency of alleles were
      determined to calculate the heterozygosity (HET) and polymorphism information
      content (PIC) values. RESULTS: We found that the HET and PIC values for the
      D16S475 marker are 0.92 and 0.91, respectively. These two values are 0.82 and
      0.80 for D16S291 and 0.50 and 0.47 for D16S3252, respectively. CONCLUSION: Based
      on this data, D16S475 and D16S291 are highly and D16S3252 is moderately
      informative for indirect genetic diagnosis of PKD1 mutations in this population.

PMID- 29026419
TI  - Effect of Vitamin D deficiency treatment on thyroid function and autoimmunity
      markers in Hashimoto's thyroiditis: A double-blind randomized placebo-controlled
      clinical trial.
AB  - BACKGROUND: The link between autoimmune thyroid diseases and Vitamin D deficiency
      has been reported. However, there are controversies in this regard. We conducted
      a double-blind randomized placebo-controlled clinical trial to investigate the
      effect of Vitamin D deficiency treatment on thyroid function and autoimmunity
      marker (thyroid peroxidase antibody [TPO-Ab]) in patients with Hashimoto's
      thyroiditis. MATERIALS AND METHODS: Fifty-six patients with Hashimoto's
      thyroiditis and Vitamin D deficiency (25-hydroxyvitamin D level <=20 ng/mL) were
      randomly allocated into two groups to receive Vitamin D (50000 IU/week, orally)
      or placebo for 12 weeks, as Vitamin D-treated (n = 30) and control (n = 26)
      groups, respectively. TPO-Ab, thyroid-stimulating hormone (TSH), parathormone,
      calcium, albumin, and creatinine concentrations were compared before and after
      trial between and within groups. The data were presented as mean (standard error
      [SE]) and analyzed by appropriate tests. RESULTS: Mean (SE) of Vitamin D was
      increased in Vitamin D-treated group (45.5 [1.8] ng/mL vs. 12.7 [0.7] ng/mL, P =
      0.01). Mean (SE) of TPO-Ab did not significantly change in both groups (734
      [102.93] IU/mL vs. 820.25 [98.92] IU/mL, P = 0.14 in Vitamin D-treated and 750.03
      [108.7] [IU/mL] vs. 838.07 [99.4] [IU/mL] in placebo-treated group, P = 0.15).
      Mean (SE) of TSH was not changed in both groups after trial, P = 0.4 and P = 0.15
      for Vitamin D-treated and control groups, respectively. No significant difference
      was observed between two study groups in none studied variables (P > 0.05).
      CONCLUSION: Vitamin D treatment in Vitamin D deficient patients with Hashimoto's
      thyroiditis could not have significant effect on thyroid function and
      autoimmunity.

PMID- 29026421
TI  - Comparison of patellar versus hamstring tendon autografts in arthroscopic
      anterior cruciate ligament reconstruction: A 6-month follow-up of a randomized
      clinical trial.
AB  - BACKGROUND: The purpose of this study was to compare the outcomes of anterior
      cruciate ligament (ACL) reconstruction using the patellar versus hamstring tendon
      (HT) autograft. MATERIALS AND METHODS: In this randomized clinical trial, fifty
      patients undergoing arthroscopic ACL reconstruction were randomized into two
      equal groups: Those treated with either autogenous patellar tendon grafts (PT
      group) or HT group grafts. All patients were reviewed immediately after surgery,
      at 6 and 12 weeks after surgery, and then at 6 months using the International
      Knee Documentation Committee evaluation form. Infection, severity of pain (visual
      analog scale), duration of rehabilitation, and clinical and magnetic resonance
      imaging (MRI) findings were assessed at the 6-month follow-up. Positive pivot
      shift and Lachman test were considered clinical signs and symptoms of treatment
      failure. In addition, the absence of the ACL or transverse ACL rather than the
      posterior oblique ligament is an MRI finding that indicates treatment failure.
      RESULTS: Comparing changes in pain and range of motion (ROM) in patients first
      and 6 months after therapy show that pain had been relief significantly (P <
      0.001) and ROM dramatically changes (P < 0.001). The average rehabilitation
      period in the PT group was 13.2 +/- 2.08 weeks whereas in the HT group, it was
      9.28 +/- 2.26 weeks. A significant difference was seen between the two groups in
      terms of the rehabilitation period (P < 0.001). No significant difference was
      found in the normal ROM between the groups (P = 0.32). When the pain severity was
      considered, a significant difference was found between the PT group and the HT
      group (P < 0.001). The HT group patients had less knee pain than did the PT group
      patients. No significant difference in infection rates was seen between two
      groups (P = 0.66). CONCLUSION: Considering the better outcomes of HT
      reconstructions for the two parameters of pain severity and rehabilitation
      period, we consider HTs to be the ideal graft choice for ACL reconstructions.

PMID- 29026422
TI  - Treatment for incarcerated indirect hernia with "Cross-Internal Ring" inguinal
      oblique incision in children.
AB  - BACKGROUND: This study aims to evaluate the utility of the "Cross-Internal Ring"
      inguinal oblique incision for the surgical treatment of incarcerated indirect
      hernia (IIH) complicated with severe abdominal distension. MATERIALS AND METHODS:
      Patients of IIH complicated with severe abdominal distension were reviewed
      retrospectively. All patients received operation through the "Cross-Internal
      Ring" inguinal oblique incision. RESULTS: There were totally 13 patients were
      included, male to female ratio was 9-4. The time for patients to resume oral
      feeding varying from 2 to 5 days after operation, no complications include
      delayed intestinal perforation, intra-abdominal abscess, and incision infection
      happened. Average postoperative hospital stay was 5.2 days. All cases were
      followed up for 6-18 months. No recurrence or iatrogenic cryptorchidism happened.
      CONCLUSION: "Cross-Internal Ring" inguinal oblique incision is a simple, safe,
      and reliable surgical method to treat pediatric IIH complicated with severe
      abdominal distension.

PMID- 29026420
TI  - Quality of life in inflammatory bowel disease patients: A cross-sectional study.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) has a significant impact on health
      related quality of life (HRQOL). This study aims to investigate the variables
      which can be attributed to HRQOL in IBD patients. MATERIALS AND METHODS: Seventy
      one patients filled in IBD questionnaire (IBDQ-32), Pittsburgh sleep quality
      index questionnaire, and sociodemographic questionnaire. Disease activity was
      assessed by Crohn's disease activity index (CDAI) and ulcerative colitis activity
      index (UCAI). The correlations of sleep quality, sociodemographic variables, and
      disease characteristics with IBDQ were investigated. RESULTS: IBDQ-32 mean score
      was lower in patients who had hospitalization (P = 0.01), poor sleep quality (P <
      0.001), anemia (P = 0.03), more severe disease (P = 0.01), and those who had not
      consumed folic acid (P = 0.01) relative to their counterparts. A multivariate
      regression analysis identified the predictors of decreased HRQOL as not consuming
      folic acid (P = 0.008), poor sleep quality (P = 0.014), and disease severity (P =
      0.043). CONCLUSION: Impaired HRQOL was significantly associated with poor sleep
      quality, lack of folic acid consumption, and disease severity in IBD patients.
      Therefore, evaluation of folic acid level and efficacy of its supplementation in
      prospective studies is recommended. Treatment of sleep disturbance with
      pharmacological agents and nonpharmacological methods should be kept in mind as
      well.

PMID- 29026423
TI  - Comprehensive maternal characteristics associated with birth weight: Bayesian
      modeling in a prospective cohort study from Iran.
AB  - BACKGROUND: In this study, we aimed to determine comprehensive maternal
      characteristics associated with birth weight using Bayesian modeling. MATERIALS
      AND METHODS: A total of 526 participants were included in this prospective study.
      Nutritional status, supplement consumption during the pregnancy, demographic and
      socioeconomic characteristics, anthropometric measures, physical activity, and
      pregnancy outcomes were considered as effective variables on the birth weight.
      Bayesian approach of complex statistical models using Markov chain Monte Carlo
      approach was used for modeling the data considering the real distribution of the
      response variable. RESULTS: There was strong positive correlation between infant
      birth weight and the maternal intake of Vitamin C, folic acid, Vitamin B3,
      Vitamin A, selenium, calcium, iron, phosphorus, potassium, magnesium as
      micronutrients, and fiber and protein as macronutrients based on the 95% high
      posterior density regions for parameters in the Bayesian model. None of the
      maternal characteristics had statistical association with birth weight.
      CONCLUSION: Higher maternal macro- and micro-nutrient intake during pregnancy was
      associated with a lower risk of delivering low birth weight infants. These
      findings support recommendations to expand intake of nutrients during pregnancy
      to high level.

PMID- 29026424
TI  - Prevalence and antibiotic resistance pattern of bacteria isolated from urinary
      tract infections in Northern Iran.
AB  - BACKGROUND: This study aimed to investigate the bacteria associated with urinary
      tract infection (UTI) and antibiotic susceptibility pattern of the isolates
      during 2013-2015 in Northern Iran. MATERIALS AND METHODS: Overall 3798 patients
      with clinical symptoms of UTI were subjected as samples, and they were cultured
      and pure isolated bacteria were identified using biochemical tests and subjected
      to antibiogram assessment using disc diffusion method. RESULTS: Totally, 568
      (14.96%) from 3798 patients had positive UTI. Four hundred and ninety-seven
      (87.5%) from 568 isolated bacteria were resistant to at least one antibiotic.
      Escherichia coli, Staphylococcus spp., and Pseudomonas spp. were the most
      prevalent bacteria. Isolated bacteria indicated the highest antibiotic resistance
      to methicillin (76.06%) and ampicillin (89.29%) and also revealed the most
      sensitivity to imipenem (99.1%) and amikacin (91.57%). Statistical analysis of
      the resistance pattern trend during 3 years indicated the insignificant increase
      (P > 0.05) in antibiotic resistance of the isolates. CONCLUSION: The results of
      this study revealed a great concern for emerging UTI-related multidrug-resistant
      strains of bacteria causing UTI in Iran.

PMID- 29026425
TI  - Effect of cytochrome P450 2C19*17 allelic variant on cardiovascular and
      cerebrovascular outcomes in clopidogrel-treated patients: A systematic review and
      meta-analysis.
AB  - BACKGROUND: We aimed to evaluate the associations of gain-of-function allele of
      CYP2C19*17 and risk of clinical events in clopidogrel-treated patients with
      cardiovascular and cerebrovascular diseases (CCVDs). MATERIALS AND METHODS:
      Literature search was conducted in PubMed, EMBASE, and Cochrane Library. Odds
      ratio (OR) combined with 95% confidence interval (CI) was the pooled statistics.
      Subgroup analysis was performed by disease type, bleeding events, and race.
      RESULTS: Thirteen eligible studies involving 14,239 patients with CYP2C19*17
      carriers or noncarriers were included in the meta-analysis. CYP2C19*17 was
      significantly related to decreased risk of major adverse cardiovascular and
      cerebrovascular events (MACCEs) in patients with coronary artery disease (CAD)
      (OR = 0.76, 95% CI: 0.60-0.98, P = 0.03), however, irrelevant with stent
      thrombosis in neither CAD nor ischemic heart disease patients. CYP2C19*17 was
      also significantly linked to decreased risk of high platelet reactivity (HPR) in
      CCVD patients (OR = 0.61, 95% CI: 0.43-0.88, P = 0.008). Meanwhile, CYP2C19*17
      was significantly associated with bleeding risk in CCVD patients (OR = 1.89, 95%
      CI: 1.09-3.25, P = 0.02) but not related to major bleeding risk (OR = 1.35, 95%
      CI: 0.87-2.08, P = 0.18). Several outcomes in Caucasian subgroup were reverse to
      the overall results, such as bleeding events and HPR, which lacked significance.
      CONCLUSION: CYP2C19*17 had a significant effect on the reduced risks of MACCE and
      HPR as well as increased bleeding risk, but not on the risks of stent thrombosis
      and major bleeding in clopidogrel-treated CCVD patients. Outcomes might be
      different in different races.

PMID- 29026427
TI  - Adoption of the Nutri-score system in France to reduce the incidence of
      noncommunicable diseases.

PMID- 29026426
TI  - Effects of nanozeolite/starch thermoplastic hydrogels on wound healing.
AB  - BACKGROUND: Wound healing is a complex biological process. Some injuries lead to
      chronic nonhealing ulcers, and healing process is a challenge to both the patient
      and the medical team. We still look forward an appropriate wound dressing.
      MATERIALS AND METHODS: In this study, starch-based nanocomposite hydrogel
      scaffolds reinforced by zeolite nanoparticles (nZ) were prepared for wound
      dressing. In addition, a herbal drug (chamomile extract) was added into the
      matrix to accelerate healing process. To estimate the cytocompatibility of
      hydrogel dressings, fibroblast mouse cells (L929) were cultured on scaffolds.
      Then, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium-bromide assay test
      and interaction of cells and scaffolds were evaluated. For evaluating healing
      process, 48 male rats were randomly divided into four groups of four animals each
      (16 rats at each step). The ulcers of the first group were treated with the same
      size of pure hydrogels. The second group received a bandage with the same size of
      hydrogel/extract/4 wt% nZ (hydrogel NZE). The third group was treated with
      chamomile extract, and the fourth group was considered as control without taking
      any medicament. Finally, the dressings were applied on the chronic refractory
      ulcers of five patients. RESULTS: After successful surface morphology and
      cytocompatibility tests, the animal study was carried out. There was a
      significant difference between starch/extract/4 wt% nZ and other groups on wound
      size decrement after day 7 (P < 0.05). At the clinical pilot study step, the
      refractory ulcers of all five patients were healed without any hypersensitivity
      reaction. CONCLUSION: Starch-based hydrogel/zeolite dressings may be safe and
      effective for chronic refractory ulcers.

PMID- 29026428
TI  - Evaluation of the physiological activity of venom from the Eurasian water shrew
      Neomys fodiens.
AB  - BACKGROUND: Animal toxins can have medical and therapeutic applications.
      Principally, toxins produced by insects, arachnids, snakes and frogs have been
      characterized. Venomous mammals are rare, and their venoms have not been
      comprehensively investigated. Among shrews, only the venom of Blarina brevicauda
      has been analysed so far, and blarina toxin has been proven to be its main toxic
      component. It is assumed that Neomys fodiens employs its venom to hunt larger
      prey. However, the toxic profile, properties and mode of action of its venom are
      largely unknown. Therefore, we analysed the cardio-, myo- and neurotropic
      properties of N. fodiens venom and saliva of non-venomous Sorex araneus (control
      tests) in vitro in physiological bioassays carried out on two model organisms:
      beetles and frogs. For the first time, we fractionated N. fodiens venom and S.
      araneus saliva by performing chromatographic separation. Next, the properties of
      selected compounds were analysed in cardiotropic bioassays in the Tenebrio
      molitor heart. RESULTS: The venom of N. fodiens caused a high decrease in the
      conduction velocity of the frog sciatic nerve, as well as a significant decrease
      in the force of frog calf muscle contraction. We also recorded a significant
      decrease in the frog heart contractile activity. Most of the selected compounds
      from N. fodiens venom displayed a positive chronotropic effect on the beetle
      heart. However, one fraction caused a strong decrease in the T. molitor heart
      contractile activity coupled with a reversible cardiac arrest. We did not observe
      any responses of the insect heart and frog organs to the saliva of S. araneus.
      Preliminary mass spectrometry analysis revealed that calmodulin-like protein,
      thymosin beta-10, hyaluronidase, lysozyme C and phospholipase A2 are present in
      the venom of N. fodiens, whereas thymosin beta4, lysozyme C and beta-defensin are
      present in S. araneus saliva. CONCLUSION: Our results showed that N. fodiens
      venom has stronger paralytic properties and lower cardioinhibitory activity.
      Therefore, it is highly probable that N. fodiens might use its venom as a prey
      immobilizing agent. We also confirmed that S. araneus is not a venomous mammal
      because its saliva did not exhibit any toxic effects.

PMID- 29026430
TI  - Gestational, perinatal, and postnatal factors that interfere with practice of
      exclusive breastfeeding by six months after birth.
AB  - BACKGROUND: Despite evidences indicating the superiority of breastfeeding and
      recent advances in the indicators of breastfeeding in Brazil, exclusive
      breastfeeding (EBF) during the first six months after birth continues to be an
      infrequent practice in the country. The objective of the present study was to
      determine which gestational, perinatal, and postnatal factors of the mother-baby
      dyad might be associated with the cessation of EBF by six months after birth.
      METHODS: Data were collected at the rooming-in facility of the Reference Center
      of Women's Health of Ribeirao Preto-Mater (CRSM-Mater) during the postpartum
      period (24 to 72 h after birth) from December 2012 to April 2013 and by telephone
      contact between the researcher and participating mothers by six months after
      birth. Questionnaires were applied to collect data, such as the practice of EBF
      in the last 24 h in the sixth month after birth. The hierarchical theoretical
      model was proposed and data were analyzed statistically by log-binomial
      regression models using SAS 9.3. RESULTS: The study involved 283 mother-baby
      dyads in which the mother evaluated did not present pregnancy-puerperal
      complications that could impede breastfeeding and confirmed the interest in
      breastfeeding her child. After the telephone contact in the exact sixth month
      after the birth of each participating baby, 84.8% of the participating mothers
      reported that they were no longer exclusively breastfeeding their babies. After
      statistical analysis, we found that there was a significant association between
      cessation of EBF and maternal report of previous experience with EBF for one
      month (0.91, 95% CI 0.81, 0.99) and six months (0.81; 95% CI 0.68, 0.94). These
      practices were associated with the maintenance of EBF and, even after adjustment
      for maternal socio-demographic variables, this association was maintained (0.85;
      95% CI 0.73, 0.99). Thus, there is a greater chance of practicing and maintaining
      EBF by six months after birth when mother had previous experience with it.
      CONCLUSION: The identification of the risk variables associated with cessation of
      EBF by six months postpartum, such as previous experience with exclusive
      breastfeeding, may contribute to the effectiveness of EBF intervention and
      support measures during the first six months after birth.

PMID- 29026431
TI  - Enablers and barriers to success among mothers planning to exclusively breastfeed
      for six months: a qualitative prospective cohort study in KwaZulu-Natal, South
      Africa.
AB  - BACKGROUND: Exclusive breastfeeding (EBF) for the first six months of life is the
      most important determinant of child health and development, and is the
      recommended feeding practice for all mothers. However, EBF rates remain low in
      South Africa. This study aimed to prospectively explore enablers or barriers to
      success among mothers who planned to exclusively breastfeed their infants for the
      first six months of life, in KwaZulu-Natal, South Africa. METHODS: A qualitative,
      longitudinal cohort design was adopted. Women were recruited during pregnancy
      from the catchment area of two hospitals (one urban and one rural) and
      purposively sampled to include working women, teenagers, and HIV positive
      pregnant women. This analysis relates to 22 women, from 30 women recruited, who
      planned antenatally to exclusively breastfeed for six months. These mothers were
      interviewed monthly for six months postpartum. Infant feeding practices were
      explored at each visit using in-depth interviews and 24 h feeding recall
      assessment. Framework analysis was conducted for qualitative data, and
      quantitative data analyzed using descriptive statistics. RESULTS: A total of 125
      interviews were conducted between November 2015 and October 2016. Among 22
      mothers who planned to exclusively breastfeed for six months, 17 reported adding
      other food or fluids before six months, and five reported exclusively
      breastfeeding successfully for the first six months. Key themes showed that all
      mothers relied strongly on health workers' infant feeding advice and support. All
      mothers experienced challenges regardless of whether they succeeded in EBF,
      including inappropriate advice from health workers, maternal-baby issues,
      pressure from family members and returning to school and work. However, those who
      were successful at EBF for six months reported that high breastfeeding self
      efficacy, HIV status and cultural meaning attached to breastfeeding were
      underlying factors for success. CONCLUSION: Health workers are key players in
      providing infant feeding information and support, yet some health workers give
      mothers infant feeding advice that is not supportive of EBF. Strategies to
      improve health workers' competency in infant feeding counselling are needed to
      better prepare pregnant women to overcome common breastfeeding challenges and
      build mothers' confidence and self-efficacy, thus increasing EBF rates.

PMID- 29026429
TI  - Markers of neuroprotection of combined EPA and DHA provided by fish oil are
      higher than those of EPA (Nannochloropsis) and DHA (Schizochytrium) from
      microalgae oils in Wistar rats.
AB  - BACKGROUND: To overcome the current overexploitation of fish rich in n-3 long
      chain polyunsaturated fatty acids (LCPUFA), microalgae have become a promising
      marine lipid source. The purpose of this study was to assess eicosapentaenoic
      acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), isolated or combined
      from distinct marine origins, on the promotion of neuroprotective effects.
      METHODS: The experiment lasted for 10 weeks and involved 32 Wistar rats, divided
      into 4 diets (n = 8): a diet rich in milk fat was taken as control (Milk Fat) and
      compared to n-3 LCPUFA enriched diets, either in EPA + DHA form through fish oil
      (Fish Oil), or EPA through Nannochloropsis oil (Nanno), or DHA through
      Schizochytrium oil (Schyzo), while maintaining Milk Fat incorporation. RESULTS:
      Plasma lipid profile and dopamine levels were more beneficial in Fish Oil diet.
      In addition, n-3 LCPUFA incorporation was found increased in liver and
      erythrocytes from Fish Oil fed rats, suggesting that fish oil is a better dietary
      source for fatty acids deposition in the organism than microalgae. The Forced
      Swimming Test revealed a positive behavioural action of EPA + DHA, in opposition
      to Milk Fat and Nanno diets, which had higher immobile times. mRNA levels of
      serotonin receptors, HT1A and HT2A along with CREB, the transmission factor for
      learning and memory, were higher in the hippocampus of rats fed n-3 LCPUFA diets
      comparative to Milk Fat. CONCLUSION: Taken together, the combination of EPA and
      DHA from fish oil can counteract the undesirable health effects of saturated fat
      based diets and benefit, in the long run, neurological function.

PMID- 29026432
TI  - Timely initiation of breastfeeding and its association with birth place in
      Ethiopia: a systematic review and meta-analysis.
AB  - BACKGROUND: Timely initiation of breastfeeding is defined as putting the newborn
      to the breast within 1 h of birth. In Ethiopia, different studies have been
      conducted to assess the prevalence of timely initiation of breastfeeding and
      associated factors. The findings of these studies were inconsistent and
      characterized by great variability. Therefore, the aim of this systematic review
      and meta-analysis was to estimate the pooled prevalence of timely initiation of
      breastfeeding and its association with birth place in Ethiopia using the
      available studies. METHODS: Databases, including PubMed, Google scholar, Science
      direct and Cochrane library were systematically searched. All original studies
      reporting the prevalence of timely initiation of breastfeeding in Ethiopia were
      considered. Two authors independently extracted all necessary data using a
      standardized data extraction format. STATA 11 statistical software was used to
      analyze the data. The Cochrane Q test statistics and I2 test were used to assess
      the heterogeneity between the studies. A random effect model was computed to
      estimate the pooled prevalence of timely initiation of breastfeeding. In
      addition, the associations between timely initiation of breastfeeding and place
      of birth were determined. RESULTS: Sixteen studies were finally included in the
      meta-analysis. The findings of this meta-analysis revealed that, the pooled
      prevalence of timely initiation of breastfeeding in Ethiopia was 61.4% (CI: 51.4,
      71.5%). The study also indicated that rural mothers had lower rate of initiating
      breastfeeding within the first 1 h after delivery as compared to their urban
      counterparts. Additionally, mothers who gave birth at health institution were
      almost 2.11 times more likely to initiate breastfeeding within 1 h as compared to
      mothers who did not give birth at health institution. CONCLUSION: In this study,
      timely initiation of breastfeeding in Ethiopia was significantly low compared to
      the current global recommendation on breastfeeding. Women from rural area were
      less likely to initiate breastfeeding within 1 h as compared with women from
      urban areas. Mothers who give birth at health institution were more likely to
      initiate breastfeeding timely.

PMID- 29026433
TI  - An optimized method for high quality DNA extraction from microalga Prototheca
      wickerhamii for genome sequencing.
AB  - BACKGROUND: The complex cell wall structure of algae often precludes efficient
      extraction of their genetic material. The purpose of this study was to design a
      next-generation sequencing-suitable DNA isolation method for unicellular,
      achlorophyllous, yeast-like microalgae of the genus Prototheca, the only known
      plant pathogens of both humans and animals. The effectiveness of the newly
      proposed scheme was compared with five other, previously described methods,
      commonly used for DNA isolation from plants and/or yeasts, available either as
      laboratory-developed, in-house assays, based on liquid nitrogen grinding or
      different enzymatic digestion, or as commercially manufactured kits. RESULTS: All
      five, previously described, isolation assays yielded DNA concentrations lower
      than those obtained with the new method, averaging 16.15 +/- 25.39 vs 74.2 +/-
      0.56 ng/uL, respectively. The new method was also superior in terms of DNA
      purity, as measured by A260/A280 (-0.41 +/- 4.26 vs 2.02 +/- 0.03), and A260/A230
      (1.20 +/- 1.12 vs 1.97 +/- 0.07) ratios. Only the liquid nitrogen-based method
      yielded DNA of comparable quantity (60.96 +/- 0.16 ng/uL) and quality (A260/A280
      = 2.08 +/- 0.02; A260/A230 = 2.23 +/- 0.26). Still, the new method showed higher
      integrity, which was best illustrated upon electrophoretic analysis. Genomic DNA
      of Prototheca wickerhamii POL-1 strain isolated with the protocol herein proposed
      was successfully sequenced on the Illumina MiSeq platform. CONCLUSIONS: A new
      method for DNA isolation from Prototheca algae is described. The method, whose
      protocol involves glass beads pulverization and cesium chloride (CsCl) density
      gradient centrifugation, was demonstrated superior over the other common assays
      in terms of DNA quantity and quality. The method is also the first to offer the
      possibility of preparation of DNA template suitable for whole genome sequencing
      of Prototheca spp.

PMID- 29026434
TI  - A plant-based chemical genomics screen for the identification of flowering
      inducers.
AB  - BACKGROUND: Floral timing is a carefully regulated process, in which the plant
      determines the optimal moment to switch from the vegetative to reproductive
      phase. While there are numerous genes known that control flowering time, little
      information is available on chemical compounds that are able to influence this
      process. We aimed to discover novel compounds that are able to induce flowering
      in the model plant Arabidopsis. For this purpose we developed a plant-based
      screening platform that can be used in a chemical genomics study. RESULTS: Here
      we describe the set-up of the screening platform and various issues and pitfalls
      that need to be addressed in order to perform a chemical genomics screening on
      Arabidopsis plantlets. We describe the choice for a molecular marker, in
      combination with a sensitive reporter that's active in plants and is sufficiently
      sensitive for detection. In this particular screen, the firefly Luciferase marker
      was used, fused to the regulatory sequences of the floral meristem identity gene
      APETALA1 (AP1), which is an early marker for flowering. Using this screening
      platform almost 9000 compounds were screened, in triplicate, in 96-well plates at
      a concentration of 25 uM. One of the identified potential flowering inducing
      compounds was studied in more detail and named Flowering1 (F1). F1 turned out to
      be an analogue of the plant hormone Salicylic acid (SA) and appeared to be more
      potent than SA in the induction of flowering. The effect could be confirmed by
      watering Arabidopsis plants with SA or F1, in which F1 gave a significant
      reduction in time to flowering in comparison to SA treatment or the control.
      CONCLUSIONS: In this study a chemical genomics screening platform was developed
      to discover compounds that can induce flowering in Arabidopsis. This platform was
      used successfully, to identify a compound that can speed-up flowering in
      Arabidopsis.

PMID- 29026435
TI  - HAlign-II: efficient ultra-large multiple sequence alignment and phylogenetic
      tree reconstruction with distributed and parallel computing.
AB  - BACKGROUND: Multiple sequence alignment (MSA) plays a key role in biological
      sequence analyses, especially in phylogenetic tree construction. Extreme increase
      in next-generation sequencing results in shortage of efficient ultra-large
      biological sequence alignment approaches for coping with different sequence
      types. METHODS: Distributed and parallel computing represents a crucial technique
      for accelerating ultra-large (e.g. files more than 1 GB) sequence analyses. Based
      on HAlign and Spark distributed computing system, we implement a highly cost
      efficient and time-efficient HAlign-II tool to address ultra-large multiple
      biological sequence alignment and phylogenetic tree construction. RESULTS: The
      experiments in the DNA and protein large scale data sets, which are more than 1GB
      files, showed that HAlign II could save time and space. It outperformed the
      current software tools. HAlign-II can efficiently carry out MSA and construct
      phylogenetic trees with ultra-large numbers of biological sequences. HAlign-II
      shows extremely high memory efficiency and scales well with increases in
      computing resource. CONCLUSIONS: THAlign-II provides a user-friendly web server
      based on our distributed computing infrastructure. HAlign-II with open-source
      codes and datasets was established at http://lab.malab.cn/soft/halign.

PMID- 29026436
TI  - Relationship between menstruation status and work conditions in Japan.
AB  - BACKGROUND: Menstrual problems can significantly impact daily and work life. In
      reaction to a shrinking population, the Japanese government is encouraging more
      women to participate in the labor force. Actual success in achieving this aim,
      however, is limited. Specifically, participation in the workforce by women during
      their reproductive years is impacted by their health, which involves not only
      work conditions, but also traditional family circumstances. Therefore, it is
      important to further assess and gather more information about the health status
      of women who work during their reproductive years in Japan. Specifically, women's
      health can be represented by menstruation status, which is a pivotal indicator.
      In this study, we assessed the association between short rest periods in work
      intervals and menstruation and other health status indicators among female
      workers in Japan. METHODS: Study participants were recruited from the alumnae of
      a university, which provided a uniform educational level. All 9864 female alumnae
      were asked to join the survey and 1630 (17%) accepted. The final sample of study
      participants (n = 505) were aged 23-43 years, had maintained the same job status
      for at least 1 year, and were not shift workers, had no maternal status, and did
      not lack any related information. The participants were divided into two groups
      according to interval time, with 11 h between end of work and resumption of daily
      work as a benchmark. This interval time was based on EU regulations and the goal
      set by the government of Japan. Health outcomes included: menstrual cycle,
      dysmenorrhoea symptoms, anxiety regarding health, and satisfaction in terms of
      health. Multiple logistic regression analyses were conducted to estimate the odds
      ratios (ORs) and 95% confidence intervals (CIs) for health indexes in association
      with interval time by adjusting for confounding variables that included both
      psychosocial and biological factors. RESULTS: We compared the health status of
      women in the workforce with and without a sufficient interval time of 11 h/day.
      Workers who had a short interval time had a significantly higher prevalence of
      anxiety about health and dissatisfaction with their health. For menstruation
      status, only abnormal menstruation cycles were observed more often among workers
      in the short interval group than those of the long interval group. However, this
      association disappeared when biological confounding factors were adjusted in a
      multivariable regression model. Dysmenorrhea symptoms did not show a
      statistically significant association with short interval time. CONCLUSIONS: This
      study found a significant association between a short interval time of less than
      11 h/day and subjective health indicators and the menstrual health status of
      women in the workforce. Menstrual health was more affected by biological factors
      than social psychological factors. A long work time and short interval time could
      increase worker anxiety and dissatisfaction and may deteriorate the menstrual
      cycle.

PMID- 29026437
TI  - Impact of a new medical network system on the efficiency of treatment for eating
      disorders in Japan: a retrospective observational study.
AB  - BACKGROUND: In Japan, patients generally have free access to any hospital or
      clinic. This could lead to reduced efficiency in the treatment for eating
      disorders (EDs) because there are only a limited number of doctors who can treat
      ED patients. The objectives of this study were to examine the efficiency of a new
      trial system for consultation and appointments, a medical community network
      (MCN), in outpatient treatment for EDs. MCN schedules appointments for the first
      visit only by referral from another medical institution, not by patients
      themselves. METHODS: We analyzed the data of 342 outpatients (mean age = 28.9 +/-
      9.9 years; 328 female and 14 male) who visited the ED clinic at the University of
      Tokyo Hospital for the first time between January 2009 and July 2012 to
      investigate possible differences in treatment efficacy between the new (MCN+)
      system and the conventional (MCN-) system, which accepts reservations directly
      from patients. RESULTS: The no-show rate for MCN+ patients (0.8%) was
      significantly lower than that for the MCN- group (17.8%) (p < 0.001). MCN+
      patients had a significantly shorter waiting period (8.4 days) for the first
      visit compared to MCN- patients (35.5 days, p < 0.001). In addition, the MCN+
      group had a much higher rate of successive visits to the clinic (p < 0.05).
      CONCLUSION: This new consultation system using a medical community network
      provided more efficient treatment for ED than did the appointment system in which
      the patients made their appointments by themselves.

PMID- 29026438
TI  - Mental health assessments in refugees and asylum seekers: evaluation of a tablet
      assisted screening software.
AB  - BACKGROUND: Mental health problems resulting from persecution and forced
      migration are very common among refugees and asylum seekers and evolve into a
      major public health challenge in hosting societies. Language barriers often
      prevent timely access to appropriate health care, leading to chronic trajectories
      and abortive social integration. Tools for multilingual screening and assessment
      could be of great benefit for this particularly vulnerable population as well as
      for policy makers. This study aimed at testing the reliability, feasibility and
      usability of the Multi-Adaptive Psychological Screening Software (MAPSS), a newly
      developed Audio Computer-Assisted Self-Interview Software (ACASI) for touchscreen
      devices, for screening purposes in a clinical setting. METHODS: In a randomized
      cross-over design including both MAPSS and paper-pencil clinician-administered
      interviews, 30 treatment-seeking refugees completed clinical measures and a
      feasibility questionnaire to rate the user interface of MAPSS. Five professionals
      performed given tasks in MAPSS and completed usability questionnaires for the
      administration interface. RESULTS: Results showed no differences between the two
      assessment modalities with regard to symptom scores. The findings suggest good
      feasibility and usability of MAPSS in traumatized refugees. The administration
      via MAPSS was significantly shorter than the paper-pencil interview. CONCLUSION:
      MAPSS may be a cost-effective, flexible and valid alternative to interpreter
      based psychometric screening and assessment.

PMID- 29026439
TI  - Priority setting for mental health research in Chile.
AB  - BACKGROUND: Scientific knowledge is a fundamental tool for making informed health
      policy decisions, but the link between health research and public policy decision
      making is often missing. This study aims to identify and prioritize a national
      set of research gaps in mental health. METHODS: A multi-approach method to
      identify gaps in knowledge was developed, including (1) document analysis and
      identification of possible research questions, (2) interviews to Ministry of
      Health key informants, (3) focus groups with different stakeholders, and (4) a
      web consultation addressed to academics. The identified gaps were translated to a
      standardized format of research questions. Criteria for prioritization were
      extracted from interviews and focus groups. Then, a team of various professionals
      applied them for scoring each question research. FINDINGS: Fifty-four people
      participated in the knowledge gaps identification process through an online
      consultation (n = 23) and focus groups (n = 18). Prioritization criteria
      identified were: extent of the knowledge gap, size of the objective population,
      potential benefit, vulnerability, urgency and applicability. 155 research
      questions were prioritized, of which 44% were related to evaluation of systems
      and/or health programs, and 26% to evaluation of interventions, including
      questions related to cost-effectiveness. 30% of the research questions came from
      the online consultation, and 36% from key informants. Users groups contributed
      with 10% of total research questions. CONCLUSION: A final priority setting for
      mental health research was reached, making available for authorities and research
      agencies a list of 155 research questions ordered by relevance. The experience
      documented here could serve to other countries interested in developing a similar
      process.

PMID- 29026440
TI  - Translating mental health diagnostic and symptom terminology to train health
      workers and engage patients in cross-cultural, non-English speaking populations.
AB  - Although there are guidelines for transcultural adaptation and validation of
      psychometric tools, similar resources do not exist for translation of diagnostic
      and symptom terminology used by health professionals to communicate with one
      another, their patients, and the public. The issue of translation is particularly
      salient when working with underserved, non-English speaking populations in high
      income countries and low- and middle-income countries. As clinicians,
      researchers, and educators working in cross-cultural settings, we present four
      recommendations to avoid common pitfalls in these settings. We demonstrate the
      need for: (1) harmonization of terminology among clinicians, educators of health
      professionals, and health policymakers; (2) distinction in terminology used among
      health professionals and that used for communication with patients, families, and
      the lay public; (3) linkage of symptom assessment with functional assessment; and
      (4) establishment of a culture of evaluating communication and terminology for
      continued improvement.

PMID- 29026441
TI  - Modeling the architecture of the regulatory system controlling methylenomycin
      production in Streptomyces coelicolor.
AB  - BACKGROUND: The antibiotic methylenomycin A is produced naturally by Streptomyces
      coelicolor A3(2), a model organism for streptomycetes. This compound is of
      particular interest to synthetic biologists because all of the associated
      biosynthetic, regulatory and resistance genes are located on a single cluster on
      the SCP1 plasmid, making the entire module easily transferable between different
      bacterial strains. Understanding further the regulation and biosynthesis of the
      methylenomycin producing gene cluster could assist in the identification of
      motifs that can be exploited in synthetic regulatory systems for the rational
      engineering of novel natural products and antibiotics. RESULTS: We identify and
      validate a plausible architecture for the regulatory system controlling
      methylenomycin production in S. coelicolor using mathematical modeling
      approaches. Model selection via an approximate Bayesian computation (ABC)
      approach identifies three candidate model architectures that are most likely to
      produce the available experimental data, from a set of 48 possible candidates.
      Subsequent global optimization of the parameters of these model architectures
      identifies a single model that most accurately reproduces the dynamical response
      of the system, as captured by time series data on methylenomycin production.
      Further analyses of variants of this model architecture that capture the effects
      of gene knockouts also reproduce qualitative experimental results observed in
      mutant S. coelicolor strains. CONCLUSIONS: The mechanistic mathematical model
      developed in this study recapitulates current biological knowledge of the
      regulation and biosynthesis of the methylenomycin producing gene cluster, and can
      be used in future studies to make testable predictions and formulate experiments
      to further improve our understanding of this complex regulatory system.

PMID- 29026442
TI  - Variation across a wheat genetic diversity panel for saccharification of
      hydrothermally pretreated straw.
AB  - BACKGROUND: Wheat straw forms an important, reliable source of lignocellulosic
      biomass for use in second-generation ethanol production. However, there is
      limited understanding of the variation in quality of straw from current breeding
      cultivars, and studies on such variation have generally employed suboptimal
      pretreatments. There is also a degree of confusion regarding phenotypic
      characteristics relevant to optimising the enzymatic saccharification of
      cellulose after suitable pretreatments for biorefining compared with those which
      determine good ruminant digestibility. The aim of this study has been to (a)
      evaluate and compare the levels of glucose enzymatically released from straw
      obtained from 89 cultivars of winter wheat after optimised hydrothermal
      pretreatments and (b) identify the underlying phenotypic characteristics relevant
      to enhanced glucose production with special reference to the ratios of
      constituent tissue types. RESULTS: Optimised pretreatment involved hydrothermal
      extraction at 210  degrees C for 10 min. Using excess cellulases, quantitative
      saccharification was achieved within 24 h. The amount of glucose released ranged
      from 192 to 275 mg/g. The extent of glucose release was correlated with (a) the
      level of internode tissue (R = 0.498; p = 6.84 * 10-7), (b) stem height (R =
      0.491; p = 1.03 * 10-6), and (c) chemical characteristics particular to stem
      tissues including higher levels of cellulose (R = 0.552; p = 2.06 * 10-8) and
      higher levels of lignin R = 0.494; p = 8.67 * 10-7. CONCLUSIONS: In order to
      achieve maximum yields of cellulosic glucose for second-generation ethanol
      production, a predisposition for wheat to produce cellulose-enriched internode
      stem tissue, particularly of longer length, would be beneficial. This contrasts
      with the ideotype for ruminant nutrition, in which an increased proportion of
      leaf tissue is preferable.

PMID- 29026443
TI  - Neutrophil killing of Staphylococcus aureus in diabetes, obesity and metabolic
      syndrome: a prospective cellular surveillance study.
AB  - BACKGROUND: Obesity, metabolic syndrome (MetS), and diabetes are frequent in
      surgical populations and can enhance susceptibility to postoperative surgical
      site infections. Reduced neutrophil function has been linked with diabetes and
      risk of Staphylococcus aureus infection. Therefore, neutrophil function in
      diabetic and obese subjects (+/- MetS) was assessed in this prospective
      serological and cellular surveillance study to determine whether vaccines
      administered to protect against infections after surgery could be effective in
      these populations. METHODS: Neutrophil function (chemotaxis, phagocytosis, and
      opsonophagocytic killing of S. aureus) was assessed in subjects classified
      according to diabetes status, body mass index, and presence/absence of MetS.
      Neutrophils were characterized within functional subsets by flow cytometry. A
      serologic assay was used to measure baseline antibody presence to each antigen in
      SA4Ag: capsular polysaccharide (CP) type 5, CP8, recombinant mutant Clumping
      factor A (rmClfA), and recombinant Manganese transport protein C (rMntC).
      RESULTS: Neutrophil function was similar for comorbid and healthy cohorts, with
      no significant between-group differences in cell counts, migration, phagocytosis
      ability, neutrophil subset proportions, and S. aureus killing ability when
      neutrophils were isolated 3-6 months apart (Visit 1 [n = 90] and Visit 2 [n =
      70]) and assessed. Median pre-existing antibody titers to CP5, CP8, and rmClfA
      were comparable for all cohorts (insufficient subjects with rMntC titers for
      determination). CONCLUSIONS: MetS, diabetes, and obesity do not impact in vitro
      neutrophil function with regard to S. aureus killing, suggesting that if an
      effective S. aureus vaccine is developed it may be effective in individuals with
      these comorbidities.

PMID- 29026444
TI  - Association of meal frequency with metabolic syndrome in Korean adults: from the
      Korea National Health and Nutrition Examination Survey (KNHANES).
AB  - BACKGROUND: Although previous studies have established a close relationship
      between caloric intake and metabolic syndrome, there is limited research
      exploring the impact of meal frequency adjusted by caloric intake on metabolic
      syndrome (MetS). OBJECTIVE: To evaluate the association of meal frequency and
      MetS after adjusting for confounding factors including caloric intake in Korean
      men and women. METHODS: We analyzed the national representative data of a total
      12,389 adults (5171 men, 7218 women) from the Korean National Health and
      Nutrition Examination Survey (KNHANES) 2010-2012. Subjects were categorized as
      eating 3 meals/day (MF3) or 2 or fewer meals/day (MF <= 2). Daily caloric intake
      was calculated using CAN-Pro 4.0 (The Korean Nutrition Society, Seoul, Korea).
      RESULTS: The prevalence of components of MetS differed significantly according to
      meal frequency in both men and women. In an unadjusted analysis, the prevalence
      of MetS in women was significantly higher in the MF3 group than the MF <= 2 group
      (27.5% vs. 17.8%, P < 0.001), whereas the prevalence of MetS in men did not
      differ between the MF3 and MF <= 2 groups (24.6% vs. 22.7%, P = 0.281). However,
      after adjusting for age, caloric intake, smoking status, alcohol consumption,
      physical activity, income, and education level, men in the MF <= 2 group had an
      increased risk of metabolic syndrome compared to men in the MF3 group (OR = 1.37,
      95%, CI = 1.12-1.67). On the other hand, meal frequency did not affect the risk
      of metabolic syndrome in women after adjusting for confounding factors including
      caloric intake (OR = 1.09, 95%, CI = 0.90-1.31). CONCLUSIONS: This study suggests
      that lower meal frequency adjusted for caloric intake, physical activity, age,
      smoking, alcohol, income, and education may be associated with increased risk of
      MetS in Korean men.

PMID- 29026445
TI  - Viral communities of the human gut: metagenomic analysis of composition and
      dynamics.
AB  - BACKGROUND: The numerically most abundant biological entities on Earth are
      viruses. Vast populations prey on the cellular microbiota in all habitats,
      including the human gut. MAIN BODY: Here we review approaches for studying the
      human virome, and some recent results on movement of viral sequences between
      bacterial cells and eukaryotic hosts. We first overview biochemical and
      bioinformatic methods, emphasizing that specific choices in the methods used can
      have strong effects on the results obtained. We then review studies
      characterizing the virome of the healthy human gut, which reveal that most of the
      viruses detected are typically uncharacterized phage - the viral dark matter -
      and that viruses that infect human cells are encountered only rarely. We then
      review movement of phage between bacterial cells during antibiotic treatment.
      Here a radical proposal for extensive movement of antibiotic genes on phage has
      been challenged by a careful reanalysis of the metagenomic annotation methods
      used. We then review two recent studies of movement of whole phage communities
      between human individuals during fecal microbial transplantation, which emphasize
      the possible role of lysogeny in dispersal. SHORT CONCLUSION: Methods for
      studying the human gut virome are improving, yielding interesting data on
      movement of phage genes between cells and mammalian host organisms. However,
      viral populations are vast, and studies of their composition and function are
      just beginning.

PMID- 29026446
TI  - DNA methylation links genetics, fetal environment, and an unhealthy lifestyle to
      the development of type 2 diabetes.
AB  - Type 2 diabetes is a complex trait with both environmental and hereditary factors
      contributing to the overall pathogenesis. One link between genes, environment,
      and disease is epigenetics influencing gene transcription and, consequently,
      organ function. Genome-wide studies have shown altered DNA methylation in tissues
      important for glucose homeostasis including pancreas, liver, skeletal muscle, and
      adipose tissue from subjects with type 2 diabetes compared with nondiabetic
      controls. Factors predisposing for type 2 diabetes including an adverse
      intrauterine environment, increasing age, overweight, physical inactivity, a
      family history of the disease, and an unhealthy diet have all shown to affect the
      DNA methylation pattern in target tissues for insulin resistance in humans.
      Epigenetics including DNA methylation may therefore improve our understanding of
      the type 2 diabetes pathogenesis, contribute to development of novel treatments,
      and be a useful tool to identify individuals at risk for developing the disease.

PMID- 29026449
TI  - Emotional impact on the results of BRCA1 and BRCA2 genetic test: an observational
      retrospective study.
AB  - BACKGROUND: BRCA1 and BRCA2 mutations are associated with a higher risk of breast
      and ovarian tumors. This study evaluated the emotional states of women 1 month
      after having received the results of the genetic test and assessed eventual
      associations with the type of outcome, personal/familiar disease history and
      major socio-demographic variables. METHODS: The study, an observational
      retrospective one, involved 91 women, evaluated 1 month after receiving their
      results. Patients were administered the Hospital Anxiety and Depression Scale,
      the Profile of Mood States and emotional Thermometers. RESULTS: Anxiety was
      significantly higher than depression (p < 0.001), and 21.3% and 21.3% of the
      sample were, respectively, possible and probable cases for anxiety, whereas 13.5%
      and 10.1% were possible and probable cases for depression. Within the six mood
      states, Confusion-Bewilderment (M = 48.5) was the lowest, whereas Fatigue-Inertia
      (M = 52.3) was the highest. Differences were recorded within the ten assessed
      emotions too. Being a proband/nonproband and being or not a cancer patient were
      associated with many tested variables. CONCLUSION: The psycho-emotional screening
      of women undertaking genetic counseling is relevant and should cover a large
      range of dimensions.

PMID- 29026448
TI  - Newborn genome-wide DNA methylation in association with pregnancy anxiety reveals
      a potential role for GABBR1.
AB  - BACKGROUND: There is increasing evidence for the role of prenatal stress in
      shaping offspring DNA methylation and disease susceptibility. In the current
      study, we aimed to identify genes and pathways associated with pregnancy anxiety
      using a genome-wide DNA methylation approach. METHODS: We selected 22 versus 23
      newborns from our Prenatal Early Life Stress (PELS) cohort, exposed to the lowest
      or highest degree of maternal pregnancy anxiety, respectively. Cord blood genome
      wide DNA methylation was assayed using the HumanMethylation450 BeadChip (HM450, n
      = 45) and candidate gene methylation using EpiTYPER (n = 80). Cortisol levels
      were measured at 2, 4, and 12 months of age to test infant stress system
      (re)activity. RESULTS: Data showed ten differentially methylated regions (DMR)
      when comparing newborns exposed to low versus high pregnancy anxiety scores. We
      validated a top DMR in the GABA-B receptor subunit 1 gene (GABBR1) revealing the
      association with pregnancy anxiety particularly in male newborns (most
      significant CpG Pearson R = 0.517, p = 0.002; average methylation Pearson R =
      0.332, p = 0.039). Cord blood GABBR1 methylation was associated with infant
      cortisol levels in response to a routine vaccination at 4 months old.
      CONCLUSIONS: In conclusion, our results show that pregnancy anxiety is associated
      with differential DNA methylation patterns in newborns and that our candidate
      gene GABBR1 is associated with infant hypothalamic-pituitary-adrenal axis
      response to a stressor. Our findings reveal a potential role for GABBR1
      methylation in association with stress and provide grounds for further research.

PMID- 29026451
TI  - Genomic insights into the thiamin metabolism of Paenibacillus thiaminolyticus
      NRRL B-4156 and P. apiarius NRRL B-23460.
AB  - Paenibacillus thiaminolyticus is the model organism for studying thiaminase I, an
      enigmatic extracellular enzyme. Originally isolated from the feces of clinical
      patients suffering from thiamin deficiency, P. thiaminolyticus has been
      implicated in thiamin deficiencies in humans and other animals due to its ability
      to produce this thiamin-degrading enzyme. Its close relative, P. apiarius, also
      produces thiaminase I and was originally isolated from dead honeybee larvae,
      though it has not been reported to be a honeybee pathogen. We generated draft
      genomes of the type strains of both species, P. thiaminolyticus NRRL B-4156 and
      P. apiarius NRRL B-23460, to deeply explore potential routes of thiamin
      metabolism. We discovered that the thiaminase I gene is located in a highly
      conserved operon with thiamin biosynthesis and salvage genes, as well as genes
      involved in the biosynthesis of the antibiotic bacimethrin. Based on metabolic
      pathway predictions, P. apiarius NRRL B-23460 has the genomic capacity to
      synthesize thiamin de novo using a pathway that is rarely seen in bacteria, but
      P. thiaminolyticus NRRL B-4156 is a thiamin auxotroph. Both genomes encode
      importers for thiamin and the pyrimidine moiety of thiamin, as well as enzymes to
      synthesize thiamin from pyrimidine and thiazole.

PMID- 29026450
TI  - Incorporating Child Maltreatment Training into Medical School Curricula.
AB  - The Child Advocacy Studies Training (CAST) program has been implemented at the
      graduate and undergraduate levels, but has not been incorporated in medical
      school training. This study examines the efficacy of a modified version of the
      CAST program that is tailored to meet the educational needs of medical students.
      A total sample of 75 first year medical students (57 at 6 month follow-up)
      participated in the study and completed analogue vignettes depicting cases of
      maltreatment. It was hypothesized that, relative to the comparison group,
      students who completed CAST training would demonstrate better accuracy at
      identifying and reporting maltreatment. Results indicated that CAST students
      demonstrated improved accuracy at the conclusion of the CAST program and 6 months
      later.

PMID- 29026452
TI  - Leveraging public health's participation in a Health Information Exchange to
      improve communicable disease reporting.
AB  - BACKGROUND: Infectious diseases can appear and spread rapidly. Timely information
      about disease patterns and trends allows public health agencies to quickly
      investigate and efficiently contain those diseases. But disease case reporting to
      public health has traditionally been paper-based, resulting in somewhat slow,
      burdensome processes. Fortunately, the expanding use of electronic health records
      and health information exchanges has created opportunities for more rapid,
      complete, and easily managed case reporting and investigation. To assess how this
      new service might impact the efficiency and quality of a public health agency's
      case investigations, we compared the timeliness of usual case investigation to
      that of case investigations based on case report forms that were partially pre
      populated with electronic data. INTERVENTION: Between September 2013-March 2014,
      chlamydia disease report forms for certain clinics in Indianapolis were
      electronically pre-populated with clinical, lab and patient data available
      through the Indiana Health Information Exchange, then provided to the
      patienta?TMs doctor. Doctors could then sign the form and deliver it to public
      health for investigation and population-level disease tracking. Methods: We
      utilized a novel matched case analysis of timeliness changes in receipt and
      processing of communicable disease report forms. Each Chlamydia cases reported
      with the pre-populated form were matched to cases reported in usual ways. We
      assessed the time from receipt of the case at the public health agency: 1)
      inclusion of the case into the public health surveillance system and 2) to close
      to case. A hierarchical random effects model was used to compare mean difference
      in each outcome between the target cases and the matched cases, with random
      intercepts for case. RESULTS: Twenty-one Chlamydia cases were reported to the
      public health agency using the pre-populated form. Sixteen of these pre-populated
      form cases were matched to at least one other case, with a mean of 23 matches per
      case. The mean Reporting Lag for the pre-populated form cases was 2.5 days, which
      was 2.7 days shorter than the mean Reporting Lag for the matched controls (p =
      <0.001). The mean time to close a pre-populated form case was 4.7 days, which was
      0.2 days shorter than time to close for the matched controls (p = 0.792).
      CONCLUSIONS: Use of pre-populated forms significantly decreased the time it took
      for the local public health agency to begin documenting and closing chlamydia
      case investigations. Thoughtful use of electronic health data for case reporting
      may decrease the per-case workload of public health agencies, and improve the
      timeliness of information about the pattern and spread of disease.

PMID- 29026447
TI  - Epigenome alterations in aortic valve stenosis and its related left ventricular
      hypertrophy.
AB  - Aortic valve stenosis is the most common cardiac valve disease, and with current
      trends in the population demographics, its prevalence is likely to rise, thus
      posing a major health and economic burden facing the worldwide societies. Over
      the past decade, it has become more than clear that our traditional genetic views
      do not sufficiently explain the well-known link between AS, proatherogenic risk
      factors, flow-induced mechanical forces, and disease-prone environmental
      influences. Recent breakthroughs in the field of epigenetics offer us a new
      perspective on gene regulation, which has broadened our perspective on etiology
      of aortic stenosis and other aortic valve diseases. Since all known epigenetic
      marks are potentially reversible this perspective is especially exciting given
      the potential for development of successful and non-invasive therapeutic
      intervention and reprogramming of cells at the epigenetic level even in the early
      stages of disease progression. This review will examine the known relationships
      between four major epigenetic mechanisms: DNA methylation, posttranslational
      histone modification, ATP-dependent chromatin remodeling, and non-coding
      regulatory RNAs, and initiation and progression of AS. Numerous profiling and
      functional studies indicate that they could contribute to endothelial
      dysfunctions, disease-prone activation of monocyte-macrophage and circulatory
      osteoprogenitor cells and activation and osteogenic transdifferentiation of
      aortic valve interstitial cells, thus leading to valvular inflammation, fibrosis,
      and calcification, and to pressure overload-induced maladaptive myocardial
      remodeling and left ventricular hypertrophy. This is especcialy the case for
      small non-coding microRNAs but was also, although in a smaller scale,
      convincingly demonstrated for other members of cellular epigenome landscape.
      Equally important, and clinically most relevant, the reported data indicate that
      epigenetic marks, particularly certain microRNA signatures, could represent
      useful non-invasive biomarkers that reflect the disease progression and patients
      prognosis for recovery after the valve replacement surgery.

PMID- 29026453
TI  - Modeling and Forecasting Influenza-like Illness (ILI) in Houston, Texas Using
      Three Surveillance Data Capture Mechanisms.
AB  - Objective The objective was to forecast and validate prediction estimates of
      influenza activity in Houston, TX using four years of historical influenza-like
      illness (ILI) from three surveillance data capture mechanisms. Background Using
      novel surveillance methods and historical data to estimate future trends of
      influenza-like illness can lead to early detection of influenza activity
      increases and decreases. Anticipating surges gives public health professionals
      more time to prepare and increase prevention efforts. Methods Data was obtained
      from three surveillance systems, Flu Near You, ILINet, and hospital emergency
      center (EC) visits, with diverse data capture mechanisms. Autoregressive
      integrated moving average (ARIMA) models were fitted to data from each source for
      week 27 of 2012 through week 26 of 2016 and used to forecast influenza-like
      activity for the subsequent 10 weeks. Estimates were then compared to actual ILI
      percentages for the same period. Results Forecasted estimates had wide confidence
      intervals that crossed zero. The forecasted trend direction differed by data
      source, resulting in lack of consensus about future influenza activity. ILINet
      forecasted estimates and actual percentages had the least differences. ILINet
      performed best when forecasting influenza activity in Houston, TX. Conclusion
      Though the three forecasted estimates did not agree on the trend directions, and
      thus, were considered imprecise predictors of long-term ILI activity based on
      existing data, pooling predictions and careful interpretations may be helpful for
      short term intervention efforts. Further work is needed to improve forecast
      accuracy considering the promise forecasting holds for seasonal influenza
      prevention and control, and pandemic preparedness.

PMID- 29026455
TI  - Interactive visualization of public health indicators to support policymaking: An
      exploratory study.
AB  - : The purpose of this study is to examine the use of interactive visualizations
      to represent data/information related to social determinants of health and public
      health indicators, and to investigate the benefits of such visualizations for
      health policymaking. METHODS: The study developed a prototype for an online
      interactive visualization tool that represents the social determinants of health.
      The study participants explored and used the tool. The tool was evaluated using
      the informal user experience evaluation method. This method involves the
      prospective users of a tool to use and play with it and their feedback to be
      collected through interviews. RESULTS: Using visualizations to represent and
      interact with health indicators has advantages over traditional representation
      techniques that do not allow users to interact with the information.
      Communicating healthcare indicators to policymakers is a complex task because of
      the complexity of the indicators, diversity of audiences, and different audience
      needs. This complexity can lead to information misinterpretation, which occurs
      when users of the health data ignore or do not know why, where, and how the data
      has been produced, or where and how it can be used. CONCLUSIONS: Public health
      policymaking is a complex process, and data is only one element among others
      needed in this complex process. Researchers and healthcare organizations should
      conduct a strategic evaluation to assess the usability of interactive
      visualizations and decision support tools before investing in these tools. Such
      evaluation should take into consideration the cost, ease of use, learnability,
      and efficiency of those tools, and the factors that influence policymaking.

PMID- 29026454
TI  - Opportunities and obstacles using a clinical decision support system for maternal
      care in Burkina Faso.
AB  - OBJECTIVE: Maternal and neonatal mortality is high in sub-Saharan Africa. To
      support Healthcare Workers (HCWs), a computerized decision support system (CDSS)
      was piloted at six rural maternal care units in Burkina Faso. During the two
      years of the study period, it was apparent from reports that the CDSS was not
      used regularly in clinical practice. This study aimed to explore the reasons why
      HCWs failed to use the CDSS. METHODS: A workshop, organized as group discussions
      and a plenary session, was performed with 13 participants to understand their
      experience with the CDSS and suggest improvements if pertinent. Workshop
      transcripts were analyzed thematically. Socio-demographic and usage patterns of
      the CDSS were examined by a questionnaire and analyzed descriptively. RESULTS:
      The participants reported that the contextual basic conditions for using the CDSS
      were not fulfilled. These included unreliable power supply, none user-friendly
      partograph, the CDSS was not integrated with workflow and staff lacked
      motivational incentives. Despite these limitations, the HCWs reported learning
      benefits from guidance and alerts in the CDSS. Using the CDSS enabled them to
      discover problems earlier as they learned to focus on symptoms to prevent harmful
      situations. CONCLUSION: The CDSS was not tailored to the needs and context of the
      users. The HCWs, defined their needs and suggested how the CDSS should be re
      designed. This suggests that the successful and regular usage of any CDSS in
      rural settings requires the involvement of users throughout the construction and
      pilot-testing phases and not only during the early prototype design period.

PMID- 29026456
TI  - Geographic Information Systems: Usability, Perception, and Preferences of Public
      Health Professionals.
AB  - BACKGROUND: Analyzing and visualizing health-related databases using Geographic
      Information Systems (GISs) becomes essential in controlling many public health
      problems. OBJECTIVES: To explore the perception and preferences of public health
      professionals (PHPs) about the usability of GISs in public health field. METHODS:
      For this scoping review, the investigators searched Medline Ovid, PubMed, IEEE,
      Scopus, and GeoBase databases. A total of 105 articles were identified. Nine
      articles met the inclusion criteria. RESULTS: Iterative evaluations, training,
      and involvement of GIS end users are productive in GIS usability. More
      methodologies are needed to support the validity of GIS usability studies. The
      exchange of GIS technology impacts public health policy and research positively.
      DISCUSSION: PHPs are aware of the use of GISs in the public health field, and the
      exchange of visualized health data in determining inequalities and
      inaccessibility issues. CONCLUSION: GISs are essential to control public health
      problems, if the related health datasets are analyzed carefully and if the
      mapping reports are extensively evaluated and interpreted.

PMID- 29026457
TI  - Applications of information and communications technologies to public health: A
      scoping review using the MeSH term: "public health informatics".
AB  - OBJECTIVE: To investigate the public health domains, key informatics concepts,
      and information and communications technologies (ICTs) applied in articles that
      are tagged with the MeSH term "public health informatics" and primarily focus on
      applying ICTs to public health. MATERIALS AND METHODS: The MeSH term "public
      health informatics" was searched on MEDLINE-PubMed. The results of the search
      were then screened in two steps in order to only include articles about applying
      ICTs to public health problems. First, articles were screened based on their
      titles and abstracts. Second, a full-text review was conducted to ensure the
      relevance of the included articles. All articles were charted based on public
      health domain, information technology, article type, and informatics concept.
      RESULTS: 515 articles were included. Communicable disease monitoring (N=235),
      public health policy and research (N=201), and public health awareness (N=85)
      constituted the majority of the articles. Inconsistent results were found
      regarding the validity of syndromic surveillance and the effectiveness of PHI
      integration within the healthcare systems. DISCUSSION: PHI articles with an ICT
      focus cover a wide range of themes. Collectively, the included articles
      emphasized the need for further research in interoperability, data quality,
      appropriate data sources, accessible health information, and communication. The
      limitations of the study include:1) only one database was searched; 2) by using
      MeSH tags as a selection criterion, PHI articles without the "public health
      informatics" MeSH term were excluded. CONCLUSION: Due to the multi-disciplinary
      nature of PHI, MeSH identifiers were not assigned consistently. Current MeSH
      tagged articles indicate that a comprehensive approach is required to integrate
      PHI into the healthcare system.

PMID- 29026458
TI  - Safe Opioid Prescription: A SMART on FHIR Approach to Clinical Decision Support.
AB  - : Background Prescription opioid pain medication overuse, misuse and abuse have
      been a significant contributing factor in the opioid epidemic. The rising death
      rates from opioid overdose have caused healthcare practitioners and researchers
      to work on optimizing pain therapy and limiting the prescriptions for pain
      medications. The state of New York has implemented a prescription drug monitoring
      program(PDMP), amended public health law to limit the prescription of opioids for
      acute pain and utilized the resources of the state and county health departments
      to help in curbing this epidemic. The recent publication of guidelines for
      prescription opioids from CDC [1] and ASIPP (American Society of Interventional
      pain practitioners) have independently reviewed literature and found good
      evidence of limiting opioid prescription for acute and chronic non cancer pain.
      [2] Method Over the last decade, advanced technology has increased the complexity
      of electronic health records systems leading to the development of Clinical
      Decision Support Systems (CDSS) to aid the work flow of healthcare providers.
      There are several systematic reviews on the effectiveness and utility of CDSSs. A
      common consensus is that commercially and locally developed CDSS are effective in
      improving patient measures while actual workload improvement and efficient cost
      cutting measure are not significantly improved by CDSS. Patient provider
      involvement in developing CDSS is a determinant of its success and utilization
      rates. [7] Therefore, a plug and play form of CDSS which can be implemented from
      an external platform through secure channels would be more effective. Design The
      Health Level Seven's (HL7) open licensed interoperability standard Fast Health
      Interoperability Resources (FHIR) has a platform, Substitutable Medical
      Applications and Reusable Technologies (SMART) for CDSS app development by a
      third party. [3] We adopted these open source standard to plan to develop an app
      for accessible and efficient implementation of the recently published guidelines
      for management of pain with prescription opioid medications. AIM: 

PMID- 29026459
TI  - Correction.
AB  - [This corrects the article , PMID: 28210429.].

PMID- 29026460
TI  - Stem cell therapy for nerve injury.
AB  - Peripheral nerve injury has remained a substantial clinical complication with no
      satisfactory treatment options. Despite the great development in the field of
      microsurgery, some severe types of neural injuries cannot be treated without
      causing tension to the injured nerve. Thus, current studies have focused on the
      new approaches for the treatment of peripheral nerve injuries. Stem cells with
      the ability to differentiate into a variety of cell types have brought a new
      perspective to this matter. In this review, we will discuss the use of three main
      sources of mesenchymal stem cells in the treatment of peripheral nerve injuries.

PMID- 29026461
TI  - Role of aryl hydrocarbon receptor in mesenchymal stromal cell activation: A
      minireview.
AB  - Mesenchymal stromal cells (MSCs) possess great therapeutic advantages due to
      their ability to produce a diverse array of trophic/growth factors related to
      cytoprotection and immunoregulation. MSC activation via specific receptors is a
      crucial event for these cells to exert their immunosuppressive response. The aryl
      hydrocarbon receptor (AhR) is a sensitive molecule for external signals and it is
      expressed in MSCs and, upon positive activation, may potentially regulate the MSC
      associated immunomodulatory function. Consequently, signalling pathways linked to
      AhR activation can elucidate some of the molecular cascades involved in MSC
      mediated immunosuppression. In this minireview, we have noted some important
      findings concerning MSC regulation via AhR, highlighting that its activation is
      associated with improvement in migration and immunoregulation, as well as an
      increase in pro-regenerative potential. Thus, AhR-mediated MSC activation can
      contribute to new perspectives on MSC-based therapies, particularly those
      directed at immune-associated disorders.

PMID- 29026462
TI  - Murine hepatocellular carcinoma derived stem cells reveal epithelial-to
      mesenchymal plasticity.
AB  - AIM: To establish a model to enrich and characterize stem-like cells from murine
      normal liver and hepatocellular carcinoma (HCC) cell lines and to further
      investigate stem-like cell association with epithelial-to-mesenchymal transition
      (EMT). METHODS: In this study, we utilized a stem cell conditioned serum-free
      medium to enrich stem-like cells from mouse HCC and normal liver cell lines, Hepa
      1-6 and AML12, respectively. We isolated the 3-dimensional spheres and assessed
      their stemness characteristics by evaluating the RNA levels of stemness genes and
      a cell surface stem cell marker by quantitative reverse transcriptase-PCR (qRT
      PCR). Next, we examined the relationship between stem cells and EMT using qRT
      PCR. RESULTS: Three-dimensional spheres were enriched by culturing murine HCC and
      normal hepatocyte cell lines in stem cell conditioned serum-free medium
      supplemented with epidermal growth factor, basic fibroblast growth factor and
      heparin sulfate. The 3-dimensional spheres had enhanced stemness markers such as
      Klf4 and Bmi1 and hepatic cancer stem cell (CSC) marker Cd44 compared to parental
      cells grown as adherent cultures. We report that epithelial markers E-cadherin
      and ZO-1 were downregulated, while mesenchymal markers Vimentin and Fibronectin
      were upregulated in 3-dimensional spheres. The 3-dimensional spheres also
      exhibited changes in expression of Snai, Zeb and Twist family of EMT
      transcription factors. CONCLUSION: Our novel method successfully enriched stem
      like cells which possessed an EMT phenotype. The isolation and characterization
      of murine hepatic CSCs could establish a precise target for the development of
      more effective therapies for HCC.

PMID- 29026463
TI  - T-cell allorecognition of donor glutathione S-transferase T1 in plasma cell-rich
      rejection.
AB  - AIM: To investigate the role of glutathione S-transferase T1 donor-specific T
      lymphocytes in plasma cell-rich rejection of liver allografts. METHODS: The study
      group included 22 liver transplant patients. Among them, 18 patients were
      mismatched for the glutathione S-transferase T1 (GSTT1) alleles (don+/rec-), and
      4 were matched (don+/rec+). Seven of the mismatched patients produced anti-GSTT1
      antibodies and developed plasma cell-rich rejection (former de novo immune
      hepatitis). For the detection of specific T lymphocytes, peripheral blood
      mononuclear cells were collected and stored in liquid nitrogen. The memory T cell
      response was studied by adding to the cell cultures to a mix of 39 custom-made,
      15-mer overlapping peptides, which covered the entire GSTT1 amino acid sequence.
      The specific cellular response to peptides was analyzed by flow cytometry using
      the markers CD8, CD4, IL-4 and IFNgamma. RESULTS: Activation of CD8+ T cells with
      different peptides was observed exclusively in the group of patients with plasma
      cell rich rejection (3 out of 7), with production of IL-4 and/or IFNgamma at a
      rate of 1%-4.92% depending on the peptides. The CD4+ response was most common and
      not exclusive for patients with the disease, where 5 out of 7 showed percentages
      of activated cells from 1.24% to 31.34%. Additionally, two patients without the
      disease but with the mismatch had cells that became stimulated with some peptides
      (1.45%-5.18%). Highly unexpected was the finding of a double positive CD4+CD8low
      T cell population that showed the highest degree of activation with some of the
      peptides in 7 patients with the mismatch, in 4 patients with plasma cell-rich
      rejection and in 3 patients without the disease. Unfortunately, CD4+CD8low cells
      represent 1% of the total number of lymphocytes, and stimulation could not be
      analyzed in 9 patients due to the low number of gated cells. Cells from the 4
      patients included as controls did not show activation with any of the peptides.
      CONCLUSION: Patients with GSTT1 mismatch can develop a specific T-cell response,
      but the potential role of this response in the pathogenesis of plasma cell-rich
      rejection is unknown.

PMID- 29026465
TI  - Towards Effective Pain Management: Breaking the Barriers.

PMID- 29026464
TI  - Evaluation of Doppler-ultrasonography in the diagnosis of transjugular
      intrahepatic portosystemic shunt dysfunction: A prospective study.
AB  - AIM: To prospectively evaluate the performance of Doppler-ultrasonography (US)
      for the detection of transjugular intrahepatic portosystemic shunt (TIPS)
      dysfunction within a multicenter cohort of cirrhotic patients. METHODS: This
      study was conducted in 10 french teaching hospitals. After TIPS insertion,
      angiography and liver Doppler-US were carried out every six months to detect
      dysfunction (defined by a portosystemic gradient >= 12 mmHg and/or a stent
      stenosis >= 50%). The association between ultrasonographic signs and dysfunction
      was studied by logistic random-effects models, and the diagnostic performance of
      each Doppler criterion was estimated by the bootstrap method. This study was
      approved by the ethics committee of Tours. RESULTS: Two hundred and eighteen
      pairs of examinations performed on 87 cirrhotic patients were analyzed. Variables
      significantly associated with dysfunction were: The speed of flow in the portal
      vein (P = 0.008), the reversal of flow in the right (P = 0.038) and left (P =
      0.049) portal branch, the loss of modulation of portal flow by the right atrium
      (P = 0.0005), ascites (P = 0.001) and the overall impression of the operator (P =
      0.0001). The diagnostic performances of these variables were low; sensitivity was
      < 58% and negative predictive value was < 73%. Therefore, dysfunction cannot be
      ruled out from Doppler-US. CONCLUSION: The performance of Doppler-US for the
      detection of TIPS dysfunction is poor compared to angiography. New tools are
      needed to improve diagnosis of TIPS dysfunction.

PMID- 29026466
TI  - Influenza Research in the Eastern Mediterranean Region: A Review.
AB  - Given the importance of influenza infections in the Eastern Mediterranean Region
      (EMR), we conducted a comprehensive literature review to analyze the status of
      influenza research in the region from 2012. Influenza research has gained more
      momentum recently with the emergence of H5N1 and new virus strains. Research
      covering epidemiological, veterinary, and basic science aspects is growing. More
      sequences were being generated per year, not only for diagnostic purposes but
      also for research. We included gray literature publications in our search and
      found several graduate student dissertations from Egypt, which were published on
      an online portal. However, the search revealed some weaknesses, mostly in the
      areas of study design and the lack of surveillance studies. Another weakness was
      the fact that the publications originated from very few countries, mainly Egypt
      and Iran. Although improving, influenza research in the EMR remains weak. We
      recommend encouraging countries in the EMR to conduct more influenza research
      using stronger methodologies.

PMID- 29026467
TI  - Chromogranin A as a Biochemical Marker for Neuroendocrine Tumors: A Single Center
      Experience at Royal Hospital, Oman.
AB  - OBJECTIVES: To evaluate the significance of serum chromogranin A (CgA) status in
      patients with and without different neuroendocrine tumors (NETs) by conducting a
      retrospective assessment of the diagnostic utility and limitations of CgA as a
      biomarker for NETs in a tertiary care hospital in Oman. METHODS: We conducted a
      retrospective analysis of CgA requests referred to the Clinical Biochemistry
      Laboratory, Royal Hospital, Oman over a 24-month period (April 2012 to March
      2014). During this time, 302 CgA tests for 270 patients (119 males and 151
      females; age range 11-86 years and mean+/-standard deviation (SD) 44.0+/-18.0
      years), were requested. Of these CgA tests, 245 tests were performed for 245
      patients investigated for the diagnosis of NETs, and 57 CgA tests were performed
      for 25 patients with diagnosed NETs who were undergoing follow-up. Serum CgA
      levels were analyzed using the enzyme-linked immunosorbent assay based on a cut
      off value of 22 IU/L. RESULTS: Of the 302 CgA tests reviewed, 197 (65.2%) were
      within the quoted normal range; however, 105 (34.8%) had CgA > 22 IU/L. Of the
      245 patients with first-line CgA, 38 patients (15.5%) had NET that included
      carcinoid, pheochromocytoma, pancreatic NET, adrenal adenoma, prostatic
      adenocarcinoma, gastrointestinal NET, medullary thyroid carcinoma, Schwannoma,
      lung small cell carcinoma, parathyroid adenoma, and pituitary macroadenoma. The
      mean+/-SD of CgA in these patients with NETs was 205.0+/-172.0 IU/L. Meanwhile,
      there were 45 (18.3%) patients with CgA > 22 IU/L (83.0+/-116.0 IU/L) who did not
      have NETs. The conditions/diseases included: essential hypertension, chronic
      kidney disease, heart failure, peptic ulcer, chronic diarrhea, use of proton pump
      inhibitors, and other chronic diseases (hypothyroidism, asthma, diabetes
      mellitus). Of the 25 patients with known NET who were followed-up, there were 57
      CgA results (29 with CgA <= 22 IU/L and 28 with CgA > 22 IU/L). The overall
      clinical sensitivity of CgA in the diagnosis of NETs was 84.2%, overall
      specificity was 78.2%, positive predictive value was 41.5%, negative predictive
      value was 96.4%, and overall efficiency was 79.2%. In patients with individual
      NET, a good reflection in CgA was noticed in the follow-up period following
      surgery or therapy. CONCLUSIONS: Serum CgA is a sensitive and effective
      noninvasive laboratory test for the clinical detection and management of NETs.
      Awareness of the pitfalls of the tests in patients with non-NET conditions,
      particularly chronic diseases and use of certain drugs, is important to be
      considered during the interpretation of the CgA levels.

PMID- 29026468
TI  - Awareness and Knowledge of Ionizing Radiation Risks Between Prescribed and Self
      Presenting Patients for Common Diagnostic Radiological Procedures in Bahrain.
AB  - OBJECTIVES: Between 20 to 50% of medical imaging examinations are considered
      inappropriate, and unnecessary ionizing radiation exposures may lead to cancer.
      We hypothesized that Bahraini patients who self-present for ionizing radiation
      procedures are not aware of, and lack the requisite knowledge of, the inherent
      risks associated with their use than patients prescribed for diagnostic purposes.
      We attempted to examine and compare the awareness and knowledge of the associated
      risks of ionizing radiation in common diagnostic radiological procedures between
      prescribed and self-presenting patients in Bahrain. METHODS: A cross-sectional
      survey was carried out among 416 Bahraini patients attending the radiology
      department of the Salmaniya Medical Complex (SMC), a secondary health care
      center, who had been referred by primary care physicians or self-presented to the
      center. Data was collected via face-to-face interviews. RESULTS: Prescribed
      patients (n = 358) had a better awareness than self-presenting (n = 58) patients
      on all ionizing radiation awareness statements (i.e., risks, permissible levels,
      willingness to undergo the procedure, and preference for a clinical examination
      over a radiological procedure) (p < 0.050). Of the 10 knowledge statements, the
      prescribed patients agreed on four statements than the self-presenting patients:
      preventing or minimizing exposure improves health, people can prevent or minimize
      exposure, a lifelong health concern, and radiological procedures offer best
      diagnoses compared to medical tests or procedures (p <  0.050). CONCLUSIONS:
      Bahraini patients who reported to SMC lack awareness and knowledge on ionizing
      radiation. The proportion of appropriate responses to awareness and knowledge
      questions were paltry for self-presenting patients and deficient for the
      prescribed patients in the knowledge segment alone.

PMID- 29026469
TI  - The Effectiveness of Mindfulness-based Cognitive Therapy on Psychological
      Symptoms and Quality of Life in Systemic Lupus Erythematosus Patients: ?A
      Randomized Controlled Trial.
AB  - OBJECTIVES: This study was conducted to determine the efficacy of mindfulness
      based cognitive therapy (MBCT) on psychological symptoms and quality of life
      (QoL) in patients with systemic lupus erythematosus (SLE). METHODS: We conducted
      a randomized single-blind clinical trial in patients with SLE referred from the
      Imam Ali Clinic in Shahrekord, southwest Iran. The patients (46 in total in two
      groups of 23 each) were randomly assigned into the experimental and control
      groups. Both groups underwent routine medical care, and the experimental group
      underwent eight group sessions of MBCT in addition to routine care. The patient,s
      QoL was assessed using the General Health Questionnaire-28 and 36-Item Short Form
      Health Survey before, after, and six months after intervention (follow-up).
      RESULTS: A significant difference was seen in psychological symptoms and QoL
      between MBCT and control groups immediately after the intervention and at follow
      up (p <= 0.050). However, the difference was not significant for the physical
      components of QoL (p >= 0.050). CONCLUSIONS: MBCT contributed to decreased
      psychological symptoms and improved QoL in patients with SLE with a stable effect
      on psychological symptoms and psychological components of QoL, but an unstable
      effect on physical components.

PMID- 29026470
TI  - Major Determinants of Maternal Near-Miss and Mortality at the Maternity Teaching
      Hospital, Erbil city, Iraq.
AB  - OBJECTIVES: To find out the major determinants of maternal near-miss (NM)and
      maternal deaths (MDs) in Erbil city, Iraq, by comparative analysis of maternal
      NMs and MDs. METHODS: We conducted a hospital-based cross-sectional study in the
      Maternity Teaching Hospital in Erbil city from 1 June to 31 December 2013. All
      MDs and NMs that occurred in the hospital during the study period were included
      in the study. Systematic identification of all eligible women was done. This
      identification included a baseline assessment of the severe pregnancy-related
      complications using the World Health Organization NM criteria. RESULTS: Severe
      preeclampsia and postpartum hemorrhage (PPH) constituted the highest proportions
      of complications in women with potentially life-threatening conditions (PLTCs)
      (30.5% and 30.0%, respectively). The highest mortality indexes were those for
      ruptured uterus (16.7) and severe complications of placenta previa (14.2).
      Factors that were significantly associated with MD (compared to NM) were hepatic
      dysfunction (p = 0.046), multiple/unspecified disorders (p = 0.003), arrival as
      an emergency condition by ambulance (p = 0.015), and history of previous cesarean
      section (p = 0.013). CONCLUSIONS: Severe preeclampsia and PPH are the main
      complications that lead to PLTCs. Factors found to be associated with MDs are
      hepatic dysfunction, multiple/unspecified disorders, arrival as an emergency
      condition by ambulance, and history of a previous cesarean section.

PMID- 29026471
TI  - Pertussis and Pertussis like Illness: Pediatric Experience in Oman.
AB  - OBJECTIVES: A resurgence of pertussis or whooping cough has been observed
      worldwide despite broad vaccination coverage. Pertussis like illness (PLI) refers
      to a clinical syndrome compatible with pertussis infection but lacking laboratory
      confirmation or an epidemiological link to a confirmed case. Our study aimed to
      estimate the contribution of Bordetella pertussis infection and identifying
      predictors of its diagnosis in a cohort of children with PLI. METHODS:
      Demographic and clinical information were retrospectively collected from the
      medical records of children < 13 years old and hospitalized for PLI in two
      pediatric units in Oman from 1 January 2012 to 31 December 2013. The laboratory
      data of all cases were reviewed and confirmed cases of pertussis were identified,
      analyzed, and compared with non-confirmed cases. RESULTS: A total of 131 patients
      were enrolled in this study. The majority (95.4% [125/131]) were infants. Only
      54.1% (71/131) of admitted children with PLI were tested for pertussis. The
      incidence of pertussis infection among the tested group was 16.9% (12/71) with a
      95% confidence interval 8.2-25.6. Severe illness occurred in 56.4% (74/131) of
      patients, and six were confirmed to have pertussis. Pediatric intensive care unit
      admission was required for one confirmed case of pertussis and eight cases from
      the PLI group (three were negative for pertussis, and five were not tested).
      Receiver operator characteristic curve analysis revealed that a white blood cell
      count 3 23.5 * 109/L had 96.6% specificity and lymphocytes 3 17 * 109/L had 98.3%
      specificity. CONCLUSIONS: Taking into consideration that the number tested for
      pertussis was limited, the incidence of pertussis was 16.9% (12 out of 71
      patients). Lymphocytosis can be used as a reliable predictor for the diagnosis of
      pertussis especially in the absence of specific confirmatory tests or until their
      results are available.

PMID- 29026472
TI  - Clinical Features and Antimicrobial Resistance of Bacterial Agents of Ventilator
      Associated Tracheobronchitis in Hamedan, Iran.
AB  - OBJECTIVES: Ventilator-associated tracheobronchitis (VAT) is a common cause of
      mortality and morbidity in patients admitted to intensive care units (ICUs). This
      study was conducted to evaluate the clinical course, etiology, and antimicrobial
      resistance of bacterial agents of VAT in ICUs in Hamedan, Iran. METHODS: During a
      12-month period, all patients with VAT in a medical and a surgical ICU were
      included. The criteria for the diagnosis of VAT were fever, mucus production, a
      positive culture of tracheal secretions, and the absence of lung infiltration.
      Clinical course, including changes in temperature and tracheal secretions, and
      outcomes were followed. The endotracheal aspirates were cultured on blood agar
      and chocolate agar, and antimicrobial susceptibility testing of isolates were
      performed using the disk diffusion method. RESULTS: Of the 1 070 ICU patients, 69
      (6.4%) were diagnosed with VAT. The mean interval between the patient's
      intubation and the onset of symptoms was 4.7+/-8.5 days. The mean duration of
      response to treatment was 4.9+/-4.7 days. A total of 23 patients (33.3%)
      progressed to ventilator-associated pneumonia (VAP), and 38 patients (55.0%)
      died. The most prevalent bacterial isolates included Acinetobacter baumannii
      (24.6%), Pseudomonas aeruginosa (20.2%), and Enterobacter (13.0%). P. aeruginosa
      and Enterobacter were the most prevalent bacteria in surgical ICU, and A.
      baumannii and K. pneumoniae were the most common in the medical ICU. All A.
      baumannii and Citrobacter species were multidrug-resistant (MDR). MDR pathogens
      were more prevalent in medical ICU compared to surgical ICU (p < 0.001).
      CONCLUSIONS: VAT increases the rates of progression to VAP, the need for
      tracheostomy, and the incidence of mortality in ICUs. Most bacterial agents of
      VAT are MDR. Preventive policies for VAP, including the use of ventilator care
      bundle, and appropriate empirical antibiotic therapy for VAT may reduce the
      incidence of VAP.

PMID- 29026473
TI  - Hepatitis C Genotypes in Libya: Correlation with Patients' Characteristics, Level
      of Viremia, and Degree of Liver Fibrosis.
AB  - OBJECTIVES: Our study sought to determine the distribution of hepatitis C virus
      (HCV)-genotypes among patients attending two tertiary care hospitals in Benghazi
      and Tripoli, Libya, and correlate this with patient's characteristics, viral
      load, and degree of fibrosis. METHODS: We conducted a retrospective study of 286
      HCV-RNA positive Libyan patients referred from different health care facilities
      in east and west Libya for specific HCV treatment. HCV genotyping was carried out
      by gene amplification. Liver histology was graded by Metavir score according to
      the stage of fibrosis. RESULTS: HCV genotypes 1, 2, 3, and 4 were found in 24.1%,
      10.8%, 3.4%, and 61.5% of the patients, respectively. Genotype 4 was detected
      more frequently in patients from east Libya (Benghazi) compared to west Libya
      (Tripoli) (75.9% vs. 41.6%, p = 0.245). Genotype 1 was more frequent in patients
      from west Libya compared to east Libya (34.1% vs. 16.8%, p = 0.657). There was a
      significant correlation between HCV genotype distribution and viral load.
      Patients with genotype 4 exhibited a higher degree of liver fibrosis (p < 0.001).
      CONCLUSIONS: HCV genotype 4 is the predominant genotype in Libya followed by
      genotype 1. However, as we go from the east to the west of the country, genotype
      1 increases. Genotype 4 was associated with higher level of viremia and higher
      stage of liver fibrosis. It is important to note that both genotypes 1 and 4 are
      associated with a poor response to pegylated interferon and ribavirin combination
      therapy. The findings emphasize the need to develop improved strategies in Libya
      for the successful treatment of HCV infection with novel newly available
      antiviral drugs.

PMID- 29026474
TI  - Using Growth Mixture Modeling for Clustering Asian and North African Countries on
      the Road Injury Death Trend (1990-2010).
AB  - OBJECTIVES: The physical injuries and financial implications as a result of road
      accidents have serious economic, cultural, and social effects. We conducted this
      study to determine any changes in the trend of road-accident-related deaths in
      Asian and North African countries from 1990 to 2010. METHODS: The current study
      was carried out using data from the Global Burden of Disease database. First, the
      process was assessed using the growth curve divided into six regions. Moreover,
      the classification was done based on the death rate using growth mixed modeling.
      RESULTS: The road injury death trend for men had more variations than women.
      Classification of these countries based on mortality using the latent growth
      mixture model resulted in more homogeneous classes according to trend in road
      fatalities. Disregarding gender and sex, there were four optimal classes. The
      first three classes had a decreasing trend with the third class having the
      greatest decreasing trend. South Korea and Taiwan were in this group.
      Afghanistan, Indonesia, Thailand, Iran, the UAE, Saudi Arabia, and Oman lay in
      group 4 and had an increasing trend in road injury deaths. CONCLUSIONS:
      Successful interventions that developed countries have used to avoid casualties
      of road injuries could be used in developing countries. These include passing
      laws making the use of seatbelts and child seats compulsory and determining
      appropriate speed limits.

PMID- 29026475
TI  - Human Parvovirus B19 in Children with Sickle Cell Disease; Poking the Spleen.
AB  - Parvovirus is a known culprit of transient red cell aplasia (TRCA) in children
      with sickle cell disease (SCD). Few reports have previously described the
      association between the virus and acute splenic sequestration crisis (ASSC) in
      the same patient. Here, we are shedding light on such a potentially serious
      combination by reporting two cases of siblings with SCD complicated with
      concurrent ASSC and TRCA and presenting a review of the relevant literature.

PMID- 29026476
TI  - Tenofovir-induced Leukocytoclastic Vasculitis.
AB  - Tenofovir, a nucleotide analog, is one of the first-line medications recommended
      for the treatment of active chronic hepatitis B virus infection (CHB) and as a
      primary prophylaxis to prevent hepatitis B reactivation in cases of
      immunosuppression. We report the first case of tenofovir-induced leukocytoclastic
      vasculitis (LCV). A 43-year-old obese woman, who was known to have inactive CHB,
      was diagnosed with chronic immune thrombocytopenic purpura (ITP). She was treated
      with corticosteroid therapy and was put on tenofovir to prevent hepatitis B virus
      reactivation. A month later, she developed a skin rash, described as non
      blanchable well-defined erythematous to violaceous papules and targetoid patches
      in her lower extremities. A skin biopsy showed features of LCV. The rash resolved
      completely within few days after replacing tenofovir with entecavir.

PMID- 29026477
TI  - Giant Submandibular Calculus Eroding Oral Cavity Mucosa.
AB  - Sialolithiasis is the formation of calculi or sialoliths in the salivary gland.
      It is the most common benign condition of the salivary gland. Sialolithiasis can
      occur in all salivary glands. The submandibular gland is most commonly affected
      followed by the parotid gland. Calculi commonly measure less than 10 mm. Calculi
      of more than 15 mm are termed giant salivary gland calculi and are infrequently
      reported in the literature. Here, we report a case of unusually large
      submandibular gland calculus of 5 cm in greatest dimension which caused erosion
      of the oral cavity.

PMID- 29026478
TI  - Vaginal Reconstruction for Vaginal Obliteration Secondary to Stevens Johnson
      Syndrome: A Case Report and Review of Literature.
AB  - Stevens-Johnson syndrome (SJS) is a rare and acute life-threatening condition,
      which is almost always precipitated by drugs. Genital mucositis in female
      patients may also be an important cause of long-term morbidity secondary to
      mucosal scarring. We present the case of a 33-year-old nulligravid woman with
      distal vaginal synechiae necessitating a surgical approach, which occurred after
      an episode of SJS. Also, we aimed to review the literature to reveal cases which
      required surgical management for long-term genital sequelae as well as discuss
      preventive measures.

PMID- 29026479
TI  - It is Always Darkest Before Dawn.

PMID- 29026480
TI  - Dhat Syndrome Among the Islamic Populations of India and Pakistan.

PMID- 29026481
TI  - The Impact of Lifestyle, Diet, and Psychological Stress on Female Fertility.

PMID- 29026482
TI  - Continuity of Care.

PMID- 29026483
TI  - Hospital Charges and Continuity of Care for Outpatients with Hypertension in
      South Korea: A Nationwide Population-Based Cohort Study from 2002 to 2013.
AB  - BACKGROUND: Continuity of care (COC) has received attention over the past decade.
      COC has also become increasingly important for hospital managers and policy
      makers because of competitive health care market conditions. The purpose of this
      study was to assess the association between hospital charges and patients'
      continuity of care-assessed by three indices of continuity of care-among
      outpatients with hypertension in South Korea. METHODS: This study used the
      National Health Insurance Service-Cohort Sample Database from 2002 to 2013. A
      total of 247,125 participants were analyzed at baseline (2002); continuity of
      care was defined using the continuity of care index, the Herfindahl-Hirschman
      index (a new continuity of care index), and the "most frequent provider
      continuity" index. Primary analyses were based on the generalized estimating
      equation regression model, which accounts for correlation among individuals
      within each hospital. RESULTS: After adjustment for age, sex, residential region,
      patient clinical complexity level, diagnosed code, hospital type, organization
      type, number of beds, number of doctors, and year, there was a negative
      correlation between hospital charges and continuity of care index (beta=-0.163,
      P<0.0001), the Herfindahl-Hirschman index (beta=-0.105, P<0.0001), and the "most
      frequent provider continuity" index (beta=-0.131, P<0.0001). Subgroup analyses
      based on hospital type produced similar trends. CONCLUSION: For all indices
      studied, hospital charges declined gradually with increasing continuity of care.
      Our study suggests that long-term, trusting partnerships between patients and
      physicians reduce hospital costs.

PMID- 29026484
TI  - Serum Lipid Levels in Relation to Consumption of Yogurt: The 2012 Korea National
      Health and Nutrition Examination Survey.
AB  - BACKGROUND: The purpose of this study was to evaluate serum lipid levels in
      Korean adults after consumption of different types of yogurt. METHODS: Study
      subjects were 3,038 individuals (>=19 years of age) who participated in the 2012
      Korean National Health and Nutrition Examination Survey. Yogurt intake was
      assessed with a food frequency questionnaire by using the 24-hour recall method.
      We conducted complex samples general linear analysis with adjustment for
      covariates. RESULTS: The serum triglyceride levels in the group consuming viscous
      yogurt were lower than those in the group consuming non-viscous yogurt.
      CONCLUSION: Consumption of viscous yogurt is associated with low serum
      triglyceride levels in Korean adults.

PMID- 29026485
TI  - Health Behavior and Factors Associated with Depression in North Korean Adolescent
      Defectors in South Korea: The Korea Youth Risk Behavior Web-Based Survey, 2011
      2014.
AB  - BACKGROUND: The number of North Korean adolescent defectors entering South Korea
      has been increasing. The health behavior, including mental health-related
      behavior, and factors associated with depression in North Korean adolescent
      defectors residing in South Korea were investigated. METHODS: Data obtained from
      the Korea Youth Risk Behavior Web-Based Survey (2011-2014) dataset were utilized.
      In total, 206 North Korean adolescent defectors were selected, and for the
      control group, 618 matched South Korean adolescents were selected. Frequency
      analysis was used to determine the place of birth and nationality of the parents,
      chi-square tests were used to compare the general characteristics of the North
      and South Korean subjects, and multivariate logistic regressions were conducted
      to compare the health behavior of the two sets of subjects. To determine the
      factors associated with depression in the North Korean subjects, a logistic
      regression was performed. RESULTS: The North Korean adolescents reported higher
      current smoking (adjusted odds ratio [aOR], 2.54; 95% confidence interval [CI],
      1.48 to 4.35), current drinking (aOR, 1.85; 95% CI, 1.15 to 2.99), and drug use
      rates (aOR, 10.99; 95% CI, 4.04 to 29.88) than did the South Korean adolescents.
      The factors associated with depression in the North Korean adolescents were
      current smoking (aOR, 6.99; 95% CI, 1.62 to 30.06), lifetime drinking experience
      (aOR, 5.32; 95% CI, 1.51 to 18.75), and perceived stress (aOR, 4.74; 95% CI, 1.74
      to 12.90). CONCLUSION: There were differences in health behavior between the
      North and South Korean adolescents. A specialized approach for North Korean
      adolescent defectors is required to promote proper health behavior and adaptation
      to South Korean society.

PMID- 29026486
TI  - Martin's Equation as the Most Suitable Method for Estimation of Low-Density
      Lipoprotein Cholesterol Levels in Korean Adults.
AB  - BACKGROUND: Friedewald equation is the most widely used method for estimating low
      density lipoprotein cholesterol (LDL-C) level. However, due to potential over- or
      underestimation, many studies have used a modified equation. This study aimed to
      compare estimates by 4 different equations to directly measured LDL-C
      concentrations in order to propose the most appropriate method for LDL-C
      estimation in the Korean population. METHODS: We studied data of 4,350 subjects
      that included total cholesterol, high-density lipoprotein cholesterol (HDL-C),
      triglyceride (TG), and LDL-C concentrations that had been measured at one
      university hospital in Seoul. We investigated 4 equations: LDL-C by Friedewald's
      original equation (LDL-CF) and its 3 modifications. Pearson correlation analysis
      was performed to compare these estimates to the direct measurement. RESULTS:
      Pearson correlation analysis revealed a good correlation among all 4 estimated
      LDL-C values and the directly measured LDL-C value. The Pearson coefficients were
      0.951 for LDL-CF, 0.917 for LDL-C by Hatta equation (LDL-CH), 0.968 for LDL-C by
      Puavilai equation (LDL-CP), and 0.983 for LDL-C by Martin equation (LDL-CM).
      Martin equation (LDL-CM) resulted in the best approximation (mean difference from
      the direct measurement, 5.5 mg/dL; mean percentage difference from the direct
      measurement, 5.1%) and the best agreement with the direct measurement (86.1%).
      LDL-CP resulted in the second-best approximation (mean difference, 7.0 mg/dL;
      mean percentage difference, 6.2%; concordance, 82.5%). LDL-CM was found to be
      less influenced by TG and HDL-C levels than by LDL-CF. CONCLUSION: Estimates by
      Martin equation had the best agreement with direct LDL-C concentrations and both
      Martin and Puavilai equations were superior to Friedewald equation for estimating
      LDL-C concentrations in Korean adults.

PMID- 29026487
TI  - Seasonal Variations and Correlations between Vitamin D and Total Testosterone
      Levels.
AB  - BACKGROUND: Some studies have provided evidence for a possible association
      between vitamin D and testosterone levels; however, the evidence from studies in
      Koreans is inconsistent. In addition, insufficient evidence is available to
      support an association between seasonal variations in vitamin D and testosterone
      levels in Koreans. Therefore, we aimed to investigate the association between
      vitamin D and testosterone levels, and between seasonal variations in these
      levels in Korean men. METHODS: This cross-sectional study included 1,559 men,
      aged 25-86 years, who underwent a medical examination. We measured serum 25
      hydroxyvitamin D (25[OH]D) and total testosterone levels, and compared other
      laboratory test results and patient lifestyle characteristics. On the basis of
      sample collection time, we categorized patients into four seasons, and analyzed
      seasonal variability in 25(OH)D and total testosterone levels. RESULTS: The
      average participant age (+/-standard deviation) was 53.3+/-8.8 years, and the
      average serum 25(OH)D and total testosterone levels were 15.9+/-7.0 ng/mL and
      5.1+/-1.6 ng/mL, respectively. In the analysis of variance (ANOVA) model, no
      significant association was found between 25(OH)D and testosterone levels
      (P=0.51). ANOVA of the average 25(OH)D levels in season-based groups revealed
      significant seasonal variations in 25(OH)D levels (P-value for trend <0.001). No
      significant association was found between seasonal variations in total
      testosterone levels (P=0.06). However, after adjustment for confounding
      variables, total testosterone and 25(OH)D showed significant seasonal variability
      (P=0.007 and P<0.001, respectively). CONCLUSION: We found no significant
      correlation between serum 25(OH)D and total testosterone levels in Korean men.
      Moreover, serum 25(OH)D and total testosterone levels showed significant seasonal
      variations.

PMID- 29026488
TI  - A Longitudinal Study on the Effects of Negative Rearing Experiences on
      Adolescents' Social Withdrawal and Aggression.
AB  - BACKGROUND: Children who have experienced negative rearing behaviors show a lack
      of self-confidence due to emotional instability and are reserved in interpersonal
      relationships. This can lead to failure in social adaptation and a high risk of
      depression, suicide, criminal acts, and anti-social behaviors. Therefore, this
      study aims to analyze the effects of experiencing negative parental rearing
      behaviors, such as neglect and abuse, on adolescents' social withdrawal and
      aggression, by utilizing multivariate latent growth models. METHODS: Data from
      the Korean Children and Youth Panel Study (KCYPS), a survey conducted by the
      National Youth Policy Institute targeting a cohort of three different age groups
      (grade 1, grade 4, and grade 7), from 2010 to 2016 was used. Multi-stage
      stratified sampling methods were used in the KCYPS, which surveyed the students
      and parents of the selected grade levels. This study analyzed the data for grade
      7, from second year (grade 8) to fourth year (grade 10). RESULTS: Negative
      rearing experiences had a significant effect on social withdrawal and aggression,
      and this influence was shown to persist over the long term. CONCLUSION: This
      study examined the long-term developmental trajectory in the relationship between
      risk factors for adolescent development. Furthermore, the relationship between
      risk factors was shown to have not only short term but long-term effects as well,
      which reinforces the limitations of previous studies.

PMID- 29026489
TI  - Delphi Survey for Designing a Intervention Research Study on Childhood Obesity
      Prevention.
AB  - BACKGROUND: The prevalence of childhood obesity in South Korea has increased
      owing to economic improvement and the prevailing Westernized dietary pattern. As
      the incidence of chronic diseases caused by obesity is also expected to increase,
      effective interventions to prevent childhood obesity are needed. Therefore, we
      conducted a Delphi study to determine the priorities of a potential intervention
      research on childhood obesity prevention and its adequacy and feasibility.
      METHODS: The two-round Delphi technique was used with a panel of 10 childhood
      obesity experts. The panelists were asked to rate "priority populations,"
      "methods of intervention," "measurement of outcomes," "future intervention
      settings," and "duration of intervention" by using a structured questionnaire.
      Finally, a portfolio analysis was performed with the adequacy and feasibility
      indexes as the two axes. RESULTS: For priority populations, the panel favored
      "elementary," "preschool," and "middle and high school" students in this order.
      Regarding intervention settings, the panelists assigned high adequacy and
      feasibility to "childcare centers" and "home" for preschool children, "school"
      and "home" for elementary school children, and "school" for adolescents in middle
      and high school. As the age of the target population increased, the panelists
      scored increasing numbers of anthropometric, clinical, and intermediate outcomes
      as highly adequate and feasible for assessing the effectiveness of the
      intervention. CONCLUSION: According to the results of the Delphi survey, the
      highest-priority population for the research on childhood obesity prevention was
      that of elementary school students. Various settings, methods, outcome measures,
      and durations for the different age groups were also suggested.

PMID- 29026490
TI  - Carbohydrate-Deficient Transferrin as a Biomarker for Screening At-Risk Drinking
      in Elderly Men.
AB  - BACKGROUND: Carbohydrate-deficient transferrin (CDT) is a useful biomarker to
      identify excessive alcohol consumption; however, few studies have validated the
      %CDT cut-off value in elderly men. This study estimated the optimal %CDT cut-off
      value that could identify excessive alcohol consumption in men aged >=65 years.
      METHODS: This retrospective study included 120 men who visited the department of
      family medicine at Chungnam National University Hospital for health check-up
      between January 2010 and August 2013. At-risk drinking included heavy- and binge
      drinking. Heavy drinking was defined as more than seven standard drinks/wk, and
      binge drinking was defined as more than three standard drinks/d. The cut-off %CDT
      values for at-risk drinking were determined using receiver operating
      characteristic (ROC) curves. RESULTS: Based on the ROC curves, the optimal %CDT
      cut-off values in >=65-year-old men were 1.95% for at-risk drinking, 1.81% for
      heavy drinking, and 2.07% for binge drinking. The sensitivity, specificity, and
      positive and negative predictive values were 58.7%, 83.6%, 69.2%, and 76.2% for
      at-risk drinking, respectively. The AUROC were >0.7 for all three evaluated cut
      offs. CONCLUSION: Our results suggest that the %CDT cut-off value for at-risk
      drinking in elderly Korean men (>=65 years) should be readjusted to a lower value
      of 1.95%.

PMID- 29026492
TI  - Chronic Large Non Healing Ulcer: Non-Tuberculous Mycobacterial Infection of the
      Laryngopharynx.
AB  - We describe a case of non-tuberculous mycobacterial infection of the larynx in a
      previously well, immunocompetent young woman. Laryngeal mycobacterial infection
      is rare and currently accounts for less than 1% of all cases. A diagnostic
      dilemma often occurs because it may mimic laryngeal carcinoma, chronic
      laryngitis, or laryngeal candidiasis. This case highlights the importance of
      considering non-tuberculous mycobacterial infection in the differential diagnosis
      of laryngeal lesions.

PMID- 29026491
TI  - Does Economic Instability Affect Healthcare Provision? Evidence Based on the
      Urban Family Physician Program in Iran.
AB  - BACKGROUND: The main aim of this study was to evaluate the achievements of some
      important goals of Iran's urban family physician plan. This plan was implemented
      when the country experienced economic instability. We examine whether an economic
      crisis affects the efficacy of a healthcare program. METHODS: We used the
      household income and expenditures survey data for 2011 (before program
      implementation) and 2012 (after program implementation). Changes in out-of-pocket
      payments and healthcare utilization were investigated using the propensity score
      matching estimator. Furthermore, changes in inequality in these two dimensions
      were examined. RESULTS: No changes in out-of-pocket payments and healthcare
      utilization were found after the implementation of this program; however,
      inequality in out-of-pocket payments increased during the reform. CONCLUSION: The
      urban family physician program was not implemented completely and many of its
      fundamental settings were not conducted because of lack of necessary healthcare
      infrastructure and budget limitations. Family physician programs should be
      implemented under a strong healthcare infrastructure and favorable economic
      conditions.

PMID- 29026493
TI  - An Uncommon Side Effect of a Commonly Used Antibiotic: Amoxicillin-Clavulanic
      Acid Induced Hepatitis.
AB  - Amoxicillin-Clavulanic acid continues to be one of the most commonly used
      antibiotic combinations. Hepatic injury due to this antibiotic is rare. We report
      a case of amoxicillin-clavulanic acid induced hepatitis causing painless jaundice
      to bring to attention this rare side effect of this commonly used antibiotic.
      This is a case of a 62-year-old Caucasian female, who presented with acute onset
      severe painless jaundice, nausea, vomiting, and pruritus of less than 1-week
      duration. She had completed a course of amoxicillin-clavulanic acid 3 weeks prior
      to presentation. A careful history pointed to this simple diagnosis. It may be
      easily missed without an in-depth history and the patient may be subjected to
      unnecessary expensive tests. This case is reported to highlight cost conscious
      care by keeping in mind a rare side effect of the commonly used antibiotic.

PMID- 29026494
TI  - Correction: The Effect of Lifestyle Changes on Blood Pressure Control among
      Hypertensive Patients.
AB  - [This corrects the article on p. 173 in vol. 38, PMID: 28775806.].

PMID- 29026495
TI  - Recombinant production and affinity purification of the FraC pore forming toxin
      using hexa-His tag and pET expression cassette.
AB  - OBJECTIVES: A newly-introduced protein toxin from a sea anemone, namely
      fragaceatoxin C is a protein with molecular weight of 20 kDa and pore-forming
      capability against cell membranes has recently grasped great attentions for its
      function. In this study, its coding sequence cloned as a fusion protein with His
      tag for simple production and rapid purification. MATERIALS AND METHODS: After
      PCR amplification using NcoI and HindIII-harboring primers, the gene fragment was
      cloned into pET-28a(+). Escherichia coli BL21 was used for expression of
      constructed vector and toxin expression was verified by SDS-PAGE. For one-step
      purification Ni-NTA sepharose affinity chromatography was employed. For
      examination of purified toxin function, RBC hemolytic test was conducted.
      RESULTS: The results showed that the FraC-coding gene was successfully cloned
      between NcoI and HindIII restriction sites and purified with affinity
      chromatography. Densitometric analysis represented the purity of approximately
      97%. Hemolytic test indicated the purified FraC had remarkable lytic activity on
      RBC and almost lysed 50% of cells at the concentration value of 6.25 nM.
      CONCLUSION: The results indicated that not only purified toxin preserved its
      activity during expression and purification processes but also exerted its
      function at lower concentrations so that even the 0.09 nM displayed hemolytic
      effect.

PMID- 29026496
TI  - The effects of gestational and lactational exposure to Nonylphenol on c-jun, and
      c-fos expression and learning and memory in hippocampus of male F1 rat.
AB  - OBJECTIVES: To investigate the effects of Nonylphenol (NP) in pups from dams
      exposed during gestational and lactational periods on immediate early genes (c
      jun, c-fos) in hippocampus and the learning and memory of F1 rats. MATERIALS AND
      METHODS: Twenty eight pregnant dams, stratified by pregnancy date, were randomly
      assigned into 4 groups, which were gavaged with NP at the doses of 50 mg/kg/day,
      100 mg/kg/day, 200 mg/kg/day and groundnut oil, respectively. Step-down avoidance
      test, and learning and memory effects of NP were evaluated on 8-weeks-old pups.
      The expressions of c-jun and c-fos and the activities of choline
      acetyltransferase (ChAT) and acetylcholinesterase (AchE) were evaluated in
      hippocampus of pups. RESULTS: Compared to the control, reaction time (RT) that
      pups spent to jump to the platform was longer (P=0.02), the number of errors were
      higher (P=0.01), and the step-down latency was shorter in the 200 mg/kg/day NP
      treated group (P=0.04). Exposure to NP induced a significant reduction in ChAT
      activity in hippocampus in the 100 (P=0.005) and 200 mg/kg/day NP-treated groups
      (P=0.002), whereas exposure to 200 mg/kg/day caused a significant increase in
      AchE activity (P=0.004); a dose-response relationship was revealed between ChAT
      and AchE activities and NP exposure in the hippocampus of pups (r=-0.821, P=0.01;
      r=0.757, P=0.04). Exposure to NP in the 100 and 200 mg/kg/day NP-treated groups
      exhibited an increase in number of c-fos and c-jun positive cells. CONCLUSION:
      Exposure to NP might negatively affect learning and memory ability in F1 rats,
      possibly due to the alterations in the expression of c-jun and c-fos, and ChAT,
      AchE activities in hippocampus of pups.

PMID- 29026497
TI  - Methadone Replacement Therapy and Sexual Disorders among Opium Dependent Iranian
      Men: A Meta-Analysis Study.
AB  - BACKGROUND: Evaluation of sexual disorders among persons receiving methadone
      replacement therapy is of great importance, because these problems may lead to
      non-compliance and relapse. This study aimed to estimate the effect of methadone
      maintenance therapy (MMT) on sexual function among addicted Iranian men using met
      analysis. METHODS: Investigating the available data banks, relevant studies were
      identified. After exclusion of duplicates, irrelevant papers and low quality
      articles, eligible papers were entered into the meta-analysis. Prevalence and
      standardized mean difference of sexual function scores were illustrated by forest
      plots based on sexual desire, orgasm and erectile function. FINDINGS: During the
      primary search, 5341 evidences were identified. After application of the
      inclusion/exclusion criteria and quality assessment, nine papers were detected
      eligible for final meta-analysis. Total prevalence [95% confidence intervals
      (CI)] of sexual disorders and erectile dysfunction among Iranian men under
      methadone therapy were estimated as 66.3% (27.1-105.5) and 77.5% (61.9-93.1),
      respectively. The standardized mean differences (95% CI) of Sexual desire, orgasm
      and erection before and after methadone therapy were estimated as 0.16 (-0.68,
      0.99), -0.01 (-0.75, 0.74) and 0.11 (-0.41, 0.64), respectively. CONCLUSION: This
      meta-analysis showed that methadone therapy did not significantly influence the
      sexual desire, erectile function and orgasm among opium dependent men.

PMID- 29026498
TI  - A Case-Control Study of Comparison of Plasma Levels of Matrix Metalloproteinase-9
      in Inhaled Opium Addicts and Clinically Healthy Persons.
AB  - BACKGROUND: Metalloproteinase-9 exists in the basement membrane of normal tissues
      and is a major factor in cancer invasion and lymphatic metastasis. Smoking has
      been reported to increase the metalloproteinase level, but the role of opium
      consumption in metalloproteinase level has not yet been examined. The current
      research intended to examine the impacts of opium consumption on the serum levels
      of metalloproteinase. METHODS: This case-control research was conducted in Kerman
      (in the southeast of Iran), after getting medical approve by the ethics
      committee. Case group of 33 non-smokers with no active inflammatory diseases who
      had the experience of inhaled opium and its derivatives were compared with a
      control group of 40 non-smokers with no active inflammatory disease and no
      experience of inhaled opium and its derivatives. Student's t-test, mean, and chi
      square test were employed to determine the correlation between the variables.
      FINDINGS: No statistically meaningful variation was detected in plasma
      metalloproteinase concentration between the case and control groups (P = 0.160).
      Also, there was no significant relation between the plasma metalloproteinase
      concentration and urinary morphine in case groups (P = 0.410), but a
      statistically significant correlation was found between gender and
      metalloproteinase in both the case and control groups (P = 0.003). CONCLUSION:
      According to the possible role of opioid drugs in cancer and its prognosis both
      directly and through their impact on serum levels of metalloproteinase, further
      studies are suggested.

PMID- 29026499
TI  - Comparison between Homocysteine, Fibrinogen, PT, PTT, INR and CRP in Male Smokers
      with/without Addiction to Opium.
AB  - BACKGROUND: Regarding the limited studies about effects of addiction on
      coagulation factors as a risk factor for increasing coagulation, and its relation
      to coronary artery disease, we decided to investigate the effect of opium on
      inflammatory and coagulation factors in a controlled setting. METHODS: This case
      control study was performed using two groups of smoking males addicted to opium
      (27 cases) and not addicted to opium (27 cases). After collecting demographic
      data, venous blood samples were gathered and sent to laboratory for measuring
      homocysteine, fibrinogen, prothrombin time (PT), partial thromboplastin time
      (PTT), International Normalized Ratio (INR), and C-reactive protein (CRP)
      quantity. In order to analyze the data, we used independent t-test plus Mann
      Whitney test with significance level of P < 0.05. FINDINGS: The average age in
      this study was 32.2 +/- 6.2 in case group and 33.3 +/- 6.2 in control group.
      Comparing case and control groups regarding age and education showed no
      significant difference (P = 0.598 and P = 0.848, respectively). Mean daily
      smoking in case group was 7.9 +/- 5.4 and 8.1 +/- 5.0 in control group. Mean
      smoking duration in case group and control group was 10.1 +/- 6.5 and 9.0 +/- 7.2
      years, respectively. There was no significant difference between two groups
      regarding smoking duration (P = 0.567). Comparison of inflammatory and
      coagulation factors showed no significant difference except for CRP and
      fibrinogen for which P = 0.661 and P = 0.889, respectively. Consumption-based
      comparison of inflammatory and coagulation factors showed no significant
      difference except for PT in oral and inhaled consumptions which showed a
      significant difference (P = 0.035). CONCLUSION: Results of this study suggest
      that opium addiction can be an influential factor in blood parameters and can
      lead to inflammatory and coagulation processes complications.

PMID- 29026500
TI  - Effectiveness of Resilience Training on Ego-control and Hardiness of Illicit Drug
      Users.
AB  - BACKGROUND: The aim of this research was to determine the effectiveness of
      resilience training upon ego-control and hardiness of the addicted persons.
      METHODS: This was a semi-experimental study with pretest and posttest control
      groups which was conducted in Sari, Iran, during 2014-2015. Thirty persons were
      selected among 240 illicit drug users who underwent screening. Resilience
      training was performed in ten sessions for the experimental group. The Kobasa
      hardiness questionnaire and self-restraint scale (SRS) were used for data
      collection and multivariate covariance test was performed for data analysis.
      FINDINGS: According to the data, ego-control and hardiness of participants were
      improved significantly by resilience training (P < 0.001). CONCLUSION: Resilience
      training is effective upon the rate of ego-control and self-restraint and
      hardiness. This method can be used in addiction treatment clinics and residential
      centers.

PMID- 29026501
TI  - Typology of Street Substance Users' Communities in Tehran, Iran.
AB  - BACKGROUND: There are different street substance users' communities (SSUCs).
      Typology of SSUCs in Tehran, Iran was approached in this qualitative study.
      METHODS: Using content analysis and saturation principles, 22 street-outreach
      workers were recruited and interviewed. Data were analyzed using open, axial, and
      selective coding. FINDINGS: Three types of SSUCs were identified. SSUCs were
      different in geographic location, the community hierarchy, roles of residents and
      its function during a 24-hour period. Type 1: surrounded naturally by trees,
      mountains etc. or located in places like canals that make them not simply
      reachable, a nonresident smuggler (or a small group of smugglers) has the most
      power in its hierarchy, works 24 hours with at least two shifts, structured with
      special roles (nonresident smuggler, the Balancer, sex-worker, seller, armed
      guard, resident substance users and nonresident costumers). Type 2: mostly
      located in the city gardens, several nonresident smugglers with limited power,
      works 16 hours or less in a day, semi-structured with roles of nonresident drug
      dealer, sex-worker, resident substance users and nonresident costumers. Type 3:
      houses that their landlords are the resident drug dealers and let the costumers
      to use drug in the house. The substance users have to leave the house after using
      drug. The house is open less than 24 hours a day. CONCLUSION: Strategies for
      delivering harm reduction services in different types of SSUCs should be modified
      according to characteristics of these communities.

PMID- 29026502
TI  - Sexual Risk Behaviors and Condom Use Barriers in Iranian Men with Substance Use
      Disorders.
AB  - BACKGROUND: We aimed to investigate risky sexual behaviors (RSBs) and condom use
      barriers in Iranian men with substance use disorders (SUDs). METHODS: Of the
      total 1800 outpatient drug free (ODF) and methadone maintenance treatment program
      (MMTP) active centers in Tehran, Iran, six were selected to participate in the
      current study. Data were collected (n = 300 men) using three questionnaires
      including a demographic questionnaire, the Risky Sexual Behavior Questionnaire
      (RSBQ), and the Condom Barriers Scale (CBS). The statistical software R, analysis
      of variance post hoc and multivariate analysis of variance (MANOVA) logistic
      regression tests were used in data analysis. FINDINGS: The majority, (n = 194,
      64.7%) reported at least one lifetime episode of RSBs. Compared to married
      participants (23.1%), 88.5% of single and 87.0% of divorced men had a history of
      RSB. Generally, the lowest and highest subscale scores of the CBS were related to
      sexual experience (2.60 +/- 0.71) and access/availability structure (3.77 +/-
      0.54), respectively. The results of MANOVA analysis showed that there was a
      statistically significant difference between the CSB subscales based on the
      participants' education and marital status (P < 0.001). Only the partner barrier
      subscale had a significant negative relationship (P = 0.003) with RSB.
      CONCLUSION: Sexual dynamic of Iranian men with SUDs is different. Barriers to
      condom use seem to be socio-culturally determined. Culturally acceptable
      strategies need to be utilized in Iranian clinical settings reaching beyond
      simply condom accessibility for this at risk population.

PMID- 29026503
TI  - Content Analysis of the Concept of Addiction in High School Textbooks of Iran.
AB  - BACKGROUND: This research sought to determine how well the causes of addiction,
      addiction harms, and prevention of addiction have been noticed in high school
      textbooks. METHODS: We used descriptive method to select the main related
      components of the addiction concept and content analysis method for analyzing the
      content of textbooks. The study population comprised 61 secondary school
      curriculum textbooks and study sample consisted of 14 secondary school textbooks
      selected by purposeful sampling method. The tools for collecting data were
      "content analysis inventory" which its validity was confirmed by educational and
      social sciences experts and its reliability has been found to be 91%. About 67
      components were prepared for content analysis and were divided to 3 categories of
      causes, harms, and prevention of addiction. The analysis units in this study
      comprised phrases, topics, examples, course topics, words, poems, images,
      questions, tables, and exercises. FINDINGS: Results of the study showed that the
      components of the addiction concept have presented with 212 remarks in the
      textbooks. Also, the degree of attention given to any of the 3 main components of
      the addiction concept were presented as follows: causes with 52 (24.52%) remarks,
      harm with 89 (41.98%) remarks, and prevention with 71 (33.49%) remarks.
      CONCLUSION: In high school textbooks, little attention has been paid to the
      concept of addiction and mostly its biological dimension were addressed while
      social, personal, familial, and religious dimensions of addiction have been
      neglected.

PMID- 29026504
TI  - Loperamide Dependency: A Case Report.
AB  - BACKGROUND: Loperamide is used as an antidiarrheal drug and is available over-the
      counter. It cannot pass the blood-brain barrier and it does not have a
      considerable abuse potential. It can lead to dangerous cardiac arrhythmia. CASE
      REPORT: Herein, we report a 35-year-old man with a 13-year history of abusing
      opioids who had undergone detoxification for four times during this period. He
      underwent detoxification for using 200 mg loperamide daily with anticholinergic
      agents, clonidine, non-steroidal analgesics, and diazepam. No evidence of
      arrhythmia was seen in the patient. CONCLUSION: Tolerating high doses of
      loperamide could be dangerous and increases the risk of fatal cardiac
      arrhythmias.

PMID- 29026505
TI  - Indicator for Success of Obesity Reduction Programs in Adolescents: Body
      Composition or Body Mass Index? Evaluating a School-based Health Promotion
      Project after 12 Weeks of Intervention.
AB  - BACKGROUND: Obesity in adolescence is the strongest risk factor for obesity in
      adulthood. This study aimed to evaluate the effects of a comprehensive lifestyle
      intervention on different anthropometric indices in 12-16-year-old boy
      adolescents after 12 Weeks of Intervention. METHODS: A total of 96 male
      adolescents from two schools participated in this study. The schools were
      randomly assigned to intervention (53 students) and control school (43 students).
      Height and weight of students were measured and their body mass index (BMI) was
      calculated. Body fat percent (BF) and body muscle percent (BM) was assessed using
      a bioimpedance analyzer considering the age, gender, and height of students at
      baseline and after intervention. The obesity reduction intervention was
      implemented in the intervention school based on the Ottawa charter for health
      promotion. RESULTS: Twelve weeks of intervention decreased BF percent in the
      intervention group in comparison with the control group (decreased by 1.81% in
      the intervention group and increased by 0.39% in the control group, P < 0.01).
      However, weight, BMI, and BM did not change significantly. CONCLUSIONS: The
      result of this study showed that a comprehensive lifestyle intervention decreased
      the body fat percent in obese adolescents, although these changes was not
      reflected in the BMI. It is possible that BMI is not a good indicator in
      assessment of the success of obesity management intervention.

PMID- 29026506
TI  - An Analysis of Widely Viewed YouTube Videos on Anal Cancer.
AB  - BACKGROUND: Rates of anal squamous cell carcinoma have increased over recent
      decades. The aim of this study was to describe characteristics of widely viewed
      YouTube videos about anal cancer. METHODS: A total of 57 videos were identified
      and reviewed. Videos were assessed and coded with respect to date uploaded,
      upload source, gender of presenter, number of views, length in minutes, number of
      likes and dislikes, and selected aspects of content. Each video was assessed to
      determine if the sole purpose of the video was to provide information regarding
      anal cancer or existed to serve another purpose. Content related to anal cancer
      was categorized. RESULTS: The mean number of views was 23,548 (range 1014
      440,078), and the average length of videos was 8:14 min. The upload source of 57
      videos was 19 (33.3%) by consumers, 12 (21.1%) by professional, and 26 (45.6%) by
      news-based sources. More than half (n = 30; 52.6%) had the sole purpose of
      providing information. The most frequently mentioned topics were treatment (n =
      25, 43.9%), symptoms (n = 15, 26.3%), encouraging screening, human
      papillomavirus, and pain, respectively (n = 14, 26.4% for each); only 6 of the 57
      videos (10.5%) specifically mentioned prevention. None of 57 most widely viewed
      videos were uploaded by any agency of the U.S. Public Health Service or by any
      other U.S. governmental agency. CONCLUSIONS: It is important for health
      practitioners to be aware of the type of information available for their patients
      on the YouTube platform.

PMID- 29026507
TI  - Face and Content Validity of the MacArthur Competence Assessment Tool for the
      Treatment of Iranian Patients.
AB  - BACKGROUND: There is not a valid Persian tool for measuring the decision-making
      competency of patients. The aim of this study is to evaluate the face and content
      validity of the MacArthur Competence Assessment Tool for the treatment of Iranian
      Persian-speaking patients. METHODS: To assess the validity of the Persian version
      of the tool, a self-administrated questionnaire was designed. The Lawshe method
      was also used for assessing each item. Content validity ratio (CVR) and content
      validity index (CVI) were used to assess the content validity quantitatively.
      According to the experts' judgment, questions with a CVR >=0.62 and CVR <0.62
      were maintainable and unmaintainable, respectively. RESULTS: The questions were
      designed in a manner to achieve the desirable result (CVR >=0.62). The CVI scale
      (S-CVI) and CVI (S-CVI/Ave) were 0.94 (higher than 0.79). Thus, the content
      validity was confirmed. CONCLUSIONS: Since capacity assessments are usually based
      on physician's subjective judgment, they are likely to bias and therefore, with
      this suitably validated tool, we can improve judgment of physicians and health
      care providers in out- and in-patient cases.

PMID- 29026508
TI  - The association between maternal use of folic acid supplements during pregnancy
      and risk of autism spectrum disorders in children: a meta-analysis.
AB  - Previous reviews have been conducted to evaluate the association between maternal
      use of folic acid supplements during pregnancy and risk of autism spectrum
      disorders (ASD) in children, with no definitive conclusion. We therefore
      conducted a more comprehensive meta-analysis to reassess the relationship between
      folic acid and the risk of ASD. The electronic databases PubMed, Web of
      Knowledge, and Wanfang Data were carefully searched to find eligible studies as
      recent as March 2017. A random effects model was used to combine the relative
      risk (RR) with 95% confidence intervals (CI). Sensitivity analysis and
      publication bias were conducted. A total of 12 articles with 16 studies
      comprising 4514 ASD cases were included in this report. It was found that
      supplementation with folic acid during pregnancy could reduce the risk of ASD [RR
      = 0.771, 95% CI = 0.641-0.928, I2  = 59.7%, Pheterogeneity = 0.001] as compared
      to those women without folic acid supplementation. The associations were
      significant among Asian, European, and American populations. In summary, this
      comprehensive meta-analysis suggested that maternal use of folic acid supplements
      during pregnancy could significantly reduce the risk of ASD in children
      regardless of ethnicity, as compared to those women who did not supplement with
      folic acid.

PMID- 29026509
TI  - Development and evaluation of a speech-generating AAC mobile app for minimally
      verbal children with autism spectrum disorder in Mainland China.
AB  - BACKGROUND: Mobile touchscreen devices are currently being used as speech
      generating devices (SGDs) and have been shown to promote the communication
      skills, particularly the requesting skills of children with autism spectrum
      disorders (ASD) who have limited spoken language. However, no augmentative and
      alternative communication (AAC) mobile app has been developed and evaluated in
      the Chinese language in Mainland China. METHODS: We developed an AAC mobile app,
      which is the first in Mainland China, to our knowledge, named Yuudee (Chinese
      name (xiaoyudi)). Yuudee was developed using the Objective-C and Java programming
      languages. A five-phase training protocol for making requests using Yuudee was
      developed based on the Picture Exchange Communication System. We trained ten
      minimally verbal children with ASD to make requests using Yuudee and evaluated
      the effectiveness of the training. RESULTS: Yuudee has a built-in library of over
      400 pictures with corresponding spoken phrases that are divided into 39
      categories ranging from making simple requests to expressing emotions. An
      additional important feature of Yuudee is its customization functions that allow
      a parent or trainer to easily select pictures and phrases to display, create new
      pictures and phrases, and change the layouts and orders of the pictures to fit
      the personal needs of each child. Yuudee is freely available in an iOS version
      from the iTunes App Store (https://itunes.apple.com/cn/app/xiao-yu
      di/id794832934?mt=8) and in an Android version from Google Play
      (https://play.google.com/store/apps/details?id=com.supersuperstar.yuudee.vue) and
      domestic Chinese Android App stores. Three consecutive unprompted successful
      responses, which were defined as an initial training success, were achieved in at
      least three of the five phases for all ten of the evaluated children. The
      accuracy rate of a given phase was calculated for each child who achieved three
      consecutive unprompted successful responses in the phase. Seven children achieved
      at least 50% accuracy in at least two of the five phases. The other three
      children achieved at least 50% accuracy in only one phase. Two children achieved
      at least 50% accuracy in all of the phases in which they were trained.
      CONCLUSIONS: Our data suggest that Yuudee is a useful tool for helping minimally
      verbal children with ASD make requests.

PMID- 29026510
TI  - A novel system for tracking social preference dynamics in mice reveals sex- and
      strain-specific characteristics.
AB  - BACKGROUND: Deciphering the biological mechanisms underlying social behavior in
      animal models requires standard behavioral paradigms that can be unbiasedly
      employed in an observer- and laboratory-independent manner. During the past
      decade, the three-chamber test has become such a standard paradigm used to
      evaluate social preference (sociability) and social novelty preference in mice.
      This test suffers from several caveats, including its reliance on spatial
      navigation skills and negligence of behavioral dynamics. METHODS: Here, we
      present a novel experimental apparatus and an automated analysis system which
      offer an alternative to the three-chamber test while solving the aforementioned
      caveats. The custom-made apparatus is simple for production, and the analysis
      system is publically available as an open-source software, enabling its free use.
      We used this system to compare the dynamics of social behavior during the social
      preference and social novelty preference tests between male and female C57BL/6J
      mice. RESULTS: We found that in both tests, male mice keep their preference
      towards one of the stimuli for longer periods than females. We then employed our
      system to define several new parameters of social behavioral dynamics in mice and
      revealed that social preference behavior is segregated in time into two distinct
      phases. An early exploration phase, characterized by high rate of transitions
      between stimuli and short bouts of stimulus investigation, is followed by an
      interaction phase with low transition rate and prolonged interactions, mainly
      with the preferred stimulus. Finally, we compared the dynamics of social behavior
      between C57BL/6J and BTBR male mice, the latter of which are considered as
      asocial strain serving as a model for autism spectrum disorder. We found that
      BTBR mice (n = 8) showed a specific deficit in transition from the exploration
      phase to the interaction phase in the social preference test, suggesting a
      reduced tendency towards social interaction. CONCLUSIONS: We successfully
      employed our new experimental system to unravel previously unidentified sex- and
      strain-specific differences in the dynamics of social behavior in mice. Thus, the
      system presented here facilitates a more thorough and detailed analysis of social
      behavior in small rodent models, enabling a better comparison between strains and
      treatments.

PMID- 29026511
TI  - Both seed germination and seedling mortality increase with experimental warming
      and fertilization in a subarctic tundra.
AB  - Climate change is expected to force many species in arctic regions to migrate and
      track their climatic niche. This requires recruitment from seed, which currently
      shows very low rates in arctic regions, where long-lived and vegetatively
      reproducing plants dominate. Therefore, we pose the question whether recruitment
      (germination and seedling establishment) in arctic regions will significantly
      improve in a warmer world, and thus allow species to follow their climatic niche.
      We used a full factorial experiment to examine if realistic warmer temperatures
      (+3  degrees C; infrared radiation) and increased nitrogen availability (+1.4 g N
      m-2 year-1) affected germination, seedling survival and above- and below-ground
      seedling biomass in five species common in subarctic regions (Anthoxanthum
      odoratum, Betula nana, Pinus sylvestris, Solidago virgaurea, Vaccinium
      myrtillus). We found that warming increased seedling emergence in all species,
      but that subsequent mortality also increased, resulting in no net warming effect
      on seedling establishment. Warming slightly increased above-ground seedling
      biomass. Fertilization, on the other hand, did not influence seedling biomass,
      but it increased seedling establishment in B. nana while it reduced establishment
      in V. myrtillus. This may help B. nana dominate over V. myrtillus in warmer
      tundra. Surprisingly, no interactive effects between warming and fertilization
      were found. The lack of a general positive response of seedling establishment to
      warmer and more nutrient-rich conditions suggests that (sub)arctic species may
      experience difficulties in tracking their climatic niche. Predictions of future
      species distributions in arctic regions solely based on abiotic factors may
      therefore overestimate species' ranges due to their poor establishment. Also, the
      opposite response to fertilization of two key (sub)arctic dwarf shrubs, i.e. B.
      nana and V. myrtillus, could have important implications for the future
      development of arctic plant communities and argues for more research into the
      role of fertilization for plant establishment.

PMID- 29026512
TI  - The phyllochron of well-watered and water deficit mature peach trees varies with
      shoot type and vigour.
AB  - The branch construction of trees is based on phytomers, repetitive subunits
      defined as node + leaf + axillary meristem + internode. The rate at which
      phytomers are added to a shoot is termed the phyllochron, which is determined by
      genetics, endogenous regulation and environmental conditions. The phyllochron is
      fundamental to understanding the growth of plants. Most phyllochron studies on
      woody species are of young plants under controlled conditions without
      consideration for different types of shoots that are present in mature trees. In
      this 2-year field study, we investigated seasonal patterns of phyllochron
      development on both proleptic and epicormic shoots of mature peach trees (Prunus
      persica) exposed to two irrigation treatments. One treatment was not irrigated
      until significant stress was detected via water potential by pressure bombing. In
      the second treatment trees were normally irrigated with ~5.84 cm of water each
      week to match evapotranspirational loss. Midday stem water potential readings
      were regularly collected to assess the level of water stress experienced by the
      trees. Measurements of individual leaves and their corresponding internodes were
      taken along tagged proleptic and epicormic shoots three times per week from the
      beginning to the end of two growing seasons. Leaf measurements were used to
      calculate the phyllochron. The phyllochron increased as the season progressed.
      This increase could not be explained by traditionally accepted effects of
      temperature or light. The more vigorous epicormic shoots added leaves
      significantly faster than proleptic shoots on trees in both water deficit and
      normally irrigated treatments. Additionally, epicormic shoots produced leaves
      with significantly greater leaf length and leaf area. Midday stem water
      potentials were more negative in trees in the water deficit treatments only after
      proleptic shoots stopped growing. The phyllochron did increase while leaf length
      and leaf area decreased on epicormic shoots of deficit irrigated trees in the
      2010 growing season. The phyllochron of both shoot types gradually increased over
      the season, which was primarily due to an endogenous rank or shoot ageing effect.
      Differences between shoot types indicate that the phyllochron is variable among
      shoots on the same tree and is associated with shoot vigour. Water deficit
      increased the phyllochron and over all shoot growth rate.

PMID- 29026514
TI  - Longstanding unilateral dislocation of the temporomandibular joint in a 6-year
      old girl.
AB  - Unilateral longstanding dislocation of the temporomandibular joint (TMJ) is rare
      in children. These patients may demonstrate some function in opening and closing
      of the mouth due to the formation of a pseudo-joint in the dislocated position.
      In this report we describe a case of longstanding unilateral dislocation of the
      TMJ in a 6-year-old girl, highlighting the diagnostic difficulty and management
      of the condition.

PMID- 29026513
TI  - Quantification of monoterpene emission sources of a conifer species in response
      to experimental drought.
AB  - Monoterpene (MT) emissions of conifer tree species, emitted from de novo
      synthesis and storage pools, play an important role in plant ecology and
      physiology. During drought stress both emission sources are affected differently
      and with conventional measuring techniques they are difficult to separate. We
      investigated 13C labelled MT emission of eight 3-year-old Scots pine seedlings in
      a drought stress experiment using a dynamic gas exchange chamber system (Tree
      DEMON). Monoterpene, water vapour and CO2 gas exchange were measured for a 2-day
      normal watering, a 11-day treatment and a 3-day re-watering period. In each
      period all trees were 13C labelled once for 5 h. Results showed the expected
      decrease of MT, water vapour and CO2 gas exchange with decreasing soil water
      content. However, during re-watering water vapour and CO2 gas exchange recovered
      fast to pre-drought levels, whereas MT increased to a lower level compared to the
      initial non-stressed phase. The 13C labelling showed highly variable %13C values
      for different MTs, which ranged compound-specific from 0.5 to 95 % for unstressed
      trees. Overall, around 36 +/- 5 % of the total emission rate originated from de
      novo synthesized MTs during the 2-day prior to stress period. During full
      drought, the de novo fraction was reduced to 3 %. For the re-watering phase de
      novo emissions recovered only partly to 20 %, while pool emissions reached pre
      drought conditions. Thus, emissions of de novo synthesized MTs of Scots pine are
      down-regulated by soil drought rather than MT emissions from pools.

PMID- 29026515
TI  - Intussusception as a complication of bariatric surgery in pregnant patients:
      report of one case and revision of the literature.
AB  - Occlusive complications after a laparoscopic Roux-in Y gastric bypass (LRYGB),
      appear mainly as fibrous membranes of wounds, internal hernias or
      intussusception. Intussusception after a bariatric surgery occurs in 0.1-0.3% of
      the cases. We present a case of intussusception in a pregnant patient after a
      LRYGB.

PMID- 29026516
TI  - Ascending cholangitis: rare presentation of a ruptured right-sided renal
      angiomyolipoma.
AB  - We report the case of a 46-year-old female who presented to the Emergency
      Department with acute, painful obstructive jaundice, with evidence of secondary
      ascending cholangitis. Surprisingly, imaging revealed the clinical picture to be
      caused not by hepatobiliary pathology, but by external compression of the biliary
      tree from a ruptured renal angiomyolipoma (AML) of the right kidney. The patient
      remained haemodynamically stable and conservative management saw resolution of
      biliary obstruction. We believe this to be the first report of a renal AML
      presenting in this way. This report highlights the diverse spectrum of
      presentations of renal angiomyolipomas.

PMID- 29026517
TI  - Dermatofibrosarcoma protuberans coexisting in a patient with a vascular
      malformation-a rare coincidence.
AB  - Dermatofibrosarcoma protuberans with fibrosarcomatous differentiation (DFSP-FS)
      is a rare soft tissue tumor with more aggressive behavior and it is not clear
      what causes this type of skin cancer. We describe the case of a 48-year-old woman
      who was born with a vascular malformation in the sternal region and presented
      suddenly with a soft tissue sarcoma (DFSP-FS) in the same territory. She was
      initially treated by embolization as the sarcoma was misdiagnosed but the tumor
      within 6 months seemed to be growing rapidly and reached a giant dimension with
      ulceration and required surgical intervention. The patient underwent a surgical
      removal of the mass but as the pathology report included a DFSP-FS with close
      margins,a second operation was required. A wide local excision was performed and
      reconstruction of defect by using bilateral pectoralis major muscle flaps and a
      full thickness skin graft from the abdominal wall. Post operatively the patient
      was treated with radiotherapy.

PMID- 29026518
TI  - Castleman's disease: a rare presentation in a retroperitoneal accessory spleen,
      treated with a minimally invasive robotic approach.
AB  - Unicentric Castleman's disease (UCD) is a rare disorder of unknown etiology
      characterized by localized lymphoid tissue proliferation and interfollicular
      hypervascularity. A 33-year-old Caucasian female presented with vague abdominal
      discomfort and pain with pressure. Ultrasound and computed tomography detected a
      large peripancreatic mass. Robotic-assisted resection of the mass along with en
      bloc dissection of the encased left adrenal gland was done. Frozen section
      examination confirmed UCD hyaline vascular variant in a retroperitoneal accessory
      spleen. Preoperative diagnosis of UCD is difficult due to its lack of specific
      symptoms and its cytologic similarity to reactive lymphadenopathy and other
      lymphoproliferative disorders. Surgical resection is standard treatment and
      provides the pathological specimen required for diagnostic confirmation. Here,
      robotic-assisted laparoscopy allowed visualization, mobilization, precise
      resection and extraction of the mass from a difficult to access retroperitoneal
      region.

PMID- 29026519
TI  - Squamous cell carcinoma arising in familial gingival fibromatosis-a rare case
      report.
AB  - Familial gingival fibromatosis is a rare hereditary condition due to chromosomal
      abnormality which can occur as an isolated disease or as part of a syndrome and
      has an incidence of 1:350 000. This condition leads to esthetic, functional,
      psychological and masticatory disturbance of the oral cavity. Here, we present a
      case of 21-year-old female with severe enlargement of gums in maxilla and
      mandible. Deciduous teeth were erupted at normal age but the permanent teeth in
      the oral cavity were not erupted. Her grandmother, father and younger sister were
      also affected with the same condition. Incisional biopsy from the chronic
      ulcerated gingiva showed squamous cell carcinoma. Patient was referred to other
      cancer institution, where metastases to lung, bone and lymph node was detected on
      CT scan. The diagnosis was made based on clinical examination, family history and
      histopathological examination.

PMID- 29026520
TI  - Work related musculoskeletal injuries sustained by Australian osteopaths:
      qualitative analysis of effects on practitioner health, clinical practice, and
      patient care.
AB  - BACKGROUND: There is limited literature that explores the experiences of
      osteopaths injured while engaging in clinical practice. Evidence from other
      similar health professions has described the numerous effects of work-related
      musculoskeletal injuries (WRMI). Work-related musculoskeletal injury refers to
      trauma to joints, ligaments, muscles and tendons resulting from injury sustained
      while undertaking work duties. This research aimed to gain a contextualised
      understanding of the experiences of osteopaths who have sustained a work-related
      musculoskeletal injury while performing clinical practice. METHOD: This research
      used a descriptive qualitative design. Participants were recruited as part of a
      larger cross-sectional study. Thirteen Australian osteopaths who had sustained a
      work-related musculoskeletal injury consented to participate in semi-structured
      interviews during May and June 2016. Thematic analysis was used to elicit
      important themes from the interview transcripts that had been recorded and
      transcribed verbatim. The qualitative accounts provided by the participants were
      coded for the impacts of their injuries on work, home life and leisure
      activities. RESULTS: The participants provided detailed, contextual information
      about their injuries, including the contributing factors and the experience of
      living with a WRMI. The findings indicate that injured osteopaths often continue
      working because of financial commitments and their dedication to patient care.
      The participants offered insights into the challenges they faced due to the
      injury and the management strategies they used to deal with the impact on their
      work and personal life. The injuries were mostly unreported, the burden being
      carried by the participants and their families. CONCLUSION: This is the first
      research that explores the experiences of osteopaths who have sustained a WRMI.
      We anticipate that this research will encourage a broad and constructive
      discussion within the profession of the issues associated with WRMIs, including
      risk minimisation and injury prevention. Further research is warranted to
      understand the relationship between osteopaths training in ergonomics and injury
      prevention. This would lead to the development of guidelines and educational
      curricula addressing safe work for osteopaths.

PMID- 29026521
TI  - A novel data storage logic in the cloud.
AB  - Databases which store and manage long-term scientific information related to life
      science are used to store huge amounts of quantitative attributes. Introduction
      of a new entity attribute requires modification of the existing data tables and
      the programs that use these data tables. The solution is increasing the virtual
      data tables while the number of screens remains the same. The main objective of
      the present study was to introduce a logic called Joker Tao (JT) which provides
      universal data storage for cloud-based databases. It means all types of input
      data can be interpreted as an entity and attribute at the same time, in the same
      data table.

PMID- 29026522
TI  - Accurate cytogenetic biodosimetry through automated dicentric chromosome curation
      and metaphase cell selection.
AB  - Accurate digital image analysis of abnormal microscopic structures relies on high
      quality images and on minimizing the rates of false positive (FP) and negative
      objects in images. Cytogenetic biodosimetry detects dicentric chromosomes (DCs)
      that arise from exposure to ionizing radiation, and determines radiation dose
      received based on DC frequency. Improvements in automated DC recognition increase
      the accuracy of dose estimates by reclassifying FP DCs as monocentric chromosomes
      or chromosome fragments. We also present image segmentation methods to rank high
      quality digital metaphase images and eliminate suboptimal metaphase cells. A set
      of chromosome morphology segmentation methods selectively filtered out FP DCs
      arising primarily from sister chromatid separation, chromosome fragmentation, and
      cellular debris. This reduced FPs by an average of 55% and was highly specific to
      these abnormal structures (>=97.7%) in three samples. Additional filters
      selectively removed images with incomplete, highly overlapped, or missing
      metaphase cells, or with poor overall chromosome morphologies that increased FP
      rates. Image selection is optimized and FP DCs are minimized by combining
      multiple feature based segmentation filters and a novel image sorting procedure
      based on the known distribution of chromosome lengths. Applying the same image
      segmentation filtering procedures to both calibration and test samples reduced
      the average dose estimation error from 0.4 Gy to <0.2 Gy, obviating the need to
      first manually review these images. This reliable and scalable solution enables
      batch processing for multiple samples of unknown dose, and meets current
      requirements for triage radiation biodosimetry of high quality metaphase cell
      preparations.

PMID- 29026523
TI  - Medical support during an Ironman 70.3 triathlon race.
AB  - BACKGROUND: The Ironman 70.3 race is also called a half Ironman, and consists of
      1.9 km of swimming, 90.1 km of cycling, and 21.1 km of running. The authors
      provide practical insights that may be useful for medical support in future
      events by summarizing the process and results of on-scene medical care. METHODS:
      The medical post was established at the transition area between the cycling and
      running courses, which was close to the finish line, and staffed with the
      headquarters team comprised of an emergency physician, an EMT, two nurses, and an
      ambulance with a driver. The other five ambulances were located throughout the
      course. The medical staff identified participants according to their numbers when
      providing medical support, and described complaints, treatment provided, and
      disposition. When treating non-participants, gender and age were recorded instead
      of numbers. The treatment records were analyzed after the race. RESULTS: The
      medical team treated a total of 187 participants. One suffered cramps in the calf
      muscles during the swimming part of the course. Nineteen were treated for
      injuries suffered during the cycling race. A total of 159 were treated for
      injuries on the running course. Five casualties, all of which occurred during the
      cycling race, required transport to hospital. CONCLUSIONS: Medical directors
      preparing medical support during a triathlon event should expect severe injuries
      in the cycling course. In hot climates, staff may also suffer from heat injuries
      as well as runners, and proper attention should be paid to these risks.

PMID- 29026525
TI  - Recent advances in understanding and prevention of sudden cardiac death.
AB  - There have been tremendous advances in the diagnosis and treatment of heart
      disease over the last 50 years. Nevertheless, it remains the number one cause of
      death. About half of heart-related deaths occur suddenly, and in about half of
      these cases the person was unaware that they had underlying heart disease.
      Genetic heart disease accounts for only approximately 2% of sudden cardiac
      deaths, but as it typically occurs in younger people it has been a particular
      focus of activity in our quest to not only understand the underlying mechanisms
      of cardiac arrhythmogenesis but also develop better strategies for earlier
      detection and prevention. In this brief review, we will highlight trends in the
      recent literature focused on sudden cardiac death in genetic heart diseases and
      how these studies are contributing to a broader understanding of sudden death in
      the community.

PMID- 29026524
TI  - Beyond adhesion: emerging roles for integrins in control of the tumor
      microenvironment.
AB  - While integrins were originally discovered as cell adhesion receptors, recent
      studies have reinforced the concept that integrins have central roles in cancer
      that extend far beyond controlling cell adhesion and migration. Indeed, as
      transmembrane cell surface receptors that occupy a critical position at the
      interface of cellular and extracellular interactions and are capable of both
      "inside-out" and "outside-in" signaling, integrins are uniquely poised to
      regulate the cell's ability to promote, sense, and react to changes in the tumor
      microenvironment. Moreover, integrins are present on all cell types in the tumor
      microenvironment, and they have important roles in regulating intercellular
      communication. Decades of promising pre-clinical studies have implicated certain
      integrins as attractive therapeutic targets in the cancer clinic. Nevertheless,
      results of the few clinical trials that target integrins in cancer have thus far
      been disappointing. Importantly, these clinical failures likely reflect the
      emerging complexity of individual and combinatorial integrin function within both
      tumor cells and other cell types of the tumor microenvironment, together with a
      need to explore integrin-targeting agents not just as monotherapies but also as
      adjuvants to more conventional radiotherapies or chemotherapies. In this review,
      we will examine recent advances toward understanding how integrins regulate
      cancer progression, including their roles in intercellular communication and
      modulation of the tumor microenvironment. Additionally, we will discuss factors
      that underlie the limited efficacy of current efforts to target integrins in the
      cancer clinic as well as potential strategies to overcome these challenges.

PMID- 29026526
TI  - Recent advances in cerebral oximetry. Assessment of cerebral autoregulation with
      near-infrared spectroscopy: myth or reality?
AB  - In recent years, the feasibility of near-infrared spectroscopy to continuously
      assess cerebral autoregulation has gained increasing interest. By plotting
      cerebral oxygen saturation over blood pressure, clinicians can generate an index
      of autoregulation: the cerebral oximetry index (COx). Successful integration of
      this monitoring ability in daily critical care may allow clinicians to tailor
      blood pressure management to the individual patient's need and might prove to be
      a major step forward in terms of patient outcome.

PMID- 29026527
TI  - Recent advances in in vitro fertilization.
AB  - The field of assisted reproductive technology is rapidly progressing with many
      new advances in the last decade. The present review discusses methods to improve
      oocyte quality in older women and new stimulation protocols that may improve the
      number of mature oocytes retrieved during an in vitro fertilization cycle. We
      will discuss the present use of pre-implantation genetic screening (PGS) and
      finally focus on some new methods to determine endometrial receptivity. The focus
      of this review is to point out areas of technology that may be controversial or
      are new enough to require proper controlled studies for validation.

PMID- 29026528
TI  - Protein clustering for cell polarity: Par-3 as a paradigm.
AB  - The scaffold protein Par-3 ( Drosophila Bazooka) is a central organizer of cell
      polarity across animals. This review focuses on how the clustering of Par-3
      contributes to cell polarity. It begins with the Par-3 homo-oligomerization
      mechanism and its regulation by Par-1 phosphorylation. The role of polarized
      cytoskeletal networks in distributing Par-3 clusters to one end of the cell is
      then discussed, as is the subsequent maintenance of polarized Par-3 clusters
      through hindered mobility and inhibition from the opposite pole. Finally,
      specific roles of Par-3 clusters are reviewed, including the bundling of
      microtubules, the cortical docking of centrosomes, the growth and positioning of
      cadherin-catenin clusters, and the inhibition of the Par-6-aPKC kinase cassette.
      Examples are drawn from Drosophila, Caenorhabditis elegans, mammalian cell
      culture, and biochemical studies.

PMID- 29026529
TI  - Coordinating ERK signaling via the molecular scaffold Kinase Suppressor of Ras.
AB  - Many cancers, including those of the colon, lung, and pancreas, depend upon the
      signaling pathways induced by mutated and constitutively active Ras. The
      molecular scaffolds Kinase Suppressor of Ras 1 and 2 (KSR1 and KSR2) play potent
      roles in promoting Ras-mediated signaling through the Raf/MEK/ERK kinase cascade.
      Here we summarize the canonical role of KSR in cells, including its central role
      as a scaffold protein for the Raf/MEK/ERK kinase cascade, its regulation of
      various cellular pathways mediated through different binding partners, and the
      phenotypic consequences of KSR1 or KSR2 genetic inactivation. Mammalian KSR
      proteins have a demonstrated role in cellular and organismal energy balance with
      implications for cancer and obesity. Targeting KSR1 in cancer using small
      molecule inhibitors has potential for therapy with reduced toxicity to the
      patient. RNAi and small molecule screens using KSR1 as a reference standard have
      the potential to expose and target vulnerabilities in cancer. Interestingly,
      although KSR1 and KSR2 are similar in structure, KSR2 has a distinct
      physiological role in regulating energy balance. Although KSR proteins have been
      studied for two decades, additional analysis is required to elucidate both the
      regulation of these molecular scaffolds and their potent effect on the spatial
      and temporal control of ERK activation in health and disease.

PMID- 29026531
TI  - Nocturia: consequences, classification, and management.
AB  - Nocturia is a widespread condition that can negatively impact quality of sleep
      and overall health. This condition is multifactorial in nature and is best
      approached through the analysis of frequency volume charts. Through these charts,
      clinicians may classify each individual case of nocturia into one of four
      distinct categories: global polyuria, nocturnal polyuria, reduced bladder
      capacity, and mixed. Treatments should then be tailored to each individual based
      upon the category of their nocturia. In some cases, appropriate therapy will
      consist of behavioral modification techniques or addressing underlying systemic
      diseases. In other cases, medical therapy may be necessary, but, to date,
      medications have shown limited efficacy at treating nocturia.

PMID- 29026530
TI  - Recent advances in pericentriolar material organization: ordered layers and
      scaffolding gels.
AB  - The centrosome is an unusual organelle that lacks a surrounding membrane, raising
      the question of what limits its size and shape. Moreover, while electron
      microscopy (EM) has provided a detailed view of centriole architecture, there has
      been limited understanding of how the second major component of centrosomes, the
      pericentriolar material (PCM), is organized. Here, we summarize exciting recent
      findings from super-resolution fluorescence imaging, structural biology, and
      biochemical reconstitution that together reveal the presence of ordered layers
      and complex gel-like scaffolds in the PCM. Moreover, we discuss how this is
      leading to a better understanding of the process of microtubule nucleation, how
      alterations in PCM size are regulated in cycling and differentiated cells, and
      why mutations in PCM components lead to specific human pathologies.

PMID- 29026532
TI  - Origins and pathogenesis of Middle East respiratory syndrome-associated
      coronavirus: recent advances.
AB  - Middle East respiratory syndrome-associated coronavirus (MERS-CoV) has been a
      significant research focus since its discovery in 2012. Since 2012, 2,040 cases
      and 712 deaths have been recorded (as of August 11, 2017), representing a
      strikingly high case fatality rate of 36%. Over the last several years, MERS-CoV
      research has progressed in several parallel and complementary directions. This
      review will focus on three particular areas: the origins and evolution of MERS
      CoV, the challenges and achievements in the development of MERS-CoV animal
      models, and our understanding of how novel proteins unique to MERS-CoV counter
      the host immune response. The origins of MERS-CoV, likely in African bats, are
      increasingly clear, although important questions remain about the establishment
      of dromedary camels as a reservoir seeding human outbreaks. Likewise, there have
      been important advances in the development of animal models, and both non-human
      primate and mouse models that seem to recapitulate human disease are now
      available. How MERS-CoV evades and inhibits the host innate immune response
      remains less clear. Although several studies have identified MERS-CoV proteins as
      innate immune antagonists, little of this work has been conducted using live
      virus under conditions of actual infection, but rather with ectopically expressed
      proteins. Accordingly, considerable space remains for major contributions to
      understanding unique ways in which MERS-CoV interacts with and modulates the host
      response. Collectively, these areas have seen significant advances over the last
      several years but continue to offer exciting opportunities for discovery.

PMID- 28928964
TI  - The evaluation of a virtual education system based on the DeLone and McLean
      model:  A path analysis.
AB  - Background: The Internet has dramatically influenced the introduction of virtual
      education. Virtual education is a term that involves online education and e
      learning. This study was conducted to evaluate a virtual education system based
      on the DeLone and McLean model. Methods: This descriptive analytical study was
      conducted using the census method on all the students of the Nursing and
      Midwifery Department of Alborz University of Medical Sciences who had taken at
      least one online course in 2016-2017. Data were collected using a researcher-made
      questionnaire based on the DeLone and McLean model in six domains and then
      analyzed in SPSS-16 and LISREL-8.8 using the path analysis. Results: The goodness
      of fit indices (GFI) of the model represent the desirability and good fit of the
      model, and the rational nature of the adjusted relationships between the
      variables based on a conceptual model (GFI = 0.98; RMSEA = 0.014).The results
      showed that system quality has the greatest impact on the net benefits of the
      system through both direct and indirect paths (beta=0.52), service quality
      through the indirect path (beta=0.03) and user satisfaction through the direct
      path (beta=0.73). Conclusions: According to the results, system quality has the
      greatest overall impact on the net benefits of the system, both directly and
      indirectly by affecting user satisfaction and the intention to use. System
      quality should therefore be further emphasized, to use these systems more
      efficiently.

PMID- 29026535
TI  - Clinical and molecular characteristics, risk factors and outcomes of Carbapenem
      resistant Klebsiella pneumoniae bloodstream infections in the intensive care
      unit.
AB  - BACKGROUND: To analyze the clinical characteristics and outcomes of carbapenem
      resistant Klebsiella pneumoniae (CRKp) and carbapenem-susceptible K. pneumoniae
      (CSKp) bloodstream infections (BSIs), and to study the risk factors for
      development of CRKp BSI and K. pneumoniae BSI-related mortality. METHODS: A
      retrospective case control study of patients with K. pneumoniae BSI was conducted
      in the intensive care unit of the First Affiliated Hospital, Medical of College,
      Zhejiang University from January 2013 to December 2014. Carbapenem resistance was
      defined in accordance with the Clinical and Laboratory Standards Institute 2016
      guidelines. Risk factors for the development of CRKp BSI and risk factors for
      mortality due to K. pneumoniae BSI were assessed. Virulence genes were detected
      by polymerase chain reaction assay. RESULTS: In total, 48 patients were enrolled
      in the study, including 31 (65%) patients with CRKp BSI and 17 (35%) patients
      with CSKp BSI. CSKp infection was associated with more severe clinical symptoms,
      particularly a higher serum creatinine level (165.06 +/- 127.01 in the CSKp group
      vs. 93.77 +/- 84.35 MUmol/L in the CRKp group, p = 0.039), but there was no
      significant difference in prognosis between the CSKp and CRKp groups. On
      multivariate analysis, indwelling central venous catheter (p = 0.045) was the
      only factor independently associated with CRKp bacteremia. However, the mortality
      of K. pneumoniae BSI patients was not correlated with carbapenem resistance. In
      addition, the isolates had diverse clonality and different origins. The frequency
      of detection of the allS and magA virulence genes was higher in the CSKp group
      than in the CRKp group (alls p = 0.04; magA p = 0.047). CONCLUSIONS: Patients in
      the CSKp group experienced more severe clinical symptoms, although mortality did
      not differ significantly between the CRKp and CSKp groups. An indwelling central
      venous catheter was the only factor independently associated with CRKp BSI. The
      mortality of patients with K. pneumoniae BSI was not associated with carbapenem
      resistance. The frequency of virulence genes was higher in the CSKp group than in
      the CRKp group.

PMID- 29026536
TI  - Implementation of central line-associated bloodstream infection prevention
      bundles in a surgical intensive care unit using peer tutoring.
AB  - BACKGROUND: Central line-associated bloodstream infections (CLABSIs) can be
      prevented through well-coordinated, multifaceted programs. However,
      implementation of CLABSI prevention programs requires individualized strategies
      for different institutional situations, and the best strategy in resource-limited
      settings is uncertain. Peer tutoring may be an efficient and effective method
      that is applicable in such settings. METHODS: A prospective intervention was
      performed to reduce CLABSIs in a surgical intensive care unit (SICU) at a
      tertiary hospital. The core interventions consisted of implementation of
      insertion and maintenance bundles for CLABSI prevention. The overall
      interventions were guided and coordinated by active educational programs using
      peer tutoring. The CLABSI rates were compared for 9 months pre-intervention, 6
      months during the intervention and 9 months post-intervention. The CLABSI rate
      was further observed for three years after the intervention. RESULTS: The rate of
      CLABSIs per 1000 catheter-days decreased from 6.9 infections in the pre
      intervention period to 2.4 and 1.8 in the intervention (6 m; P = 0.102) and post
      intervention (9 m; P = 0.036) periods, respectively. A regression model showed a
      significantly decreasing trend in the infection rate from the pre-intervention
      period (P < 0.001), with incidence-rate ratios of 0.348 (95% confidence interval
      [CI], 0.98-1.23) in the intervention period and 0.257 (95% CI, 0.07-0.91) in the
      post-intervention period. However, after the 9-month post-intervention period,
      the yearly CLABSI rates reverted to 3.0-5.4 infections per 1000 catheter-days
      over 3 years. CONCLUSIONS: Implementation of CLABSI prevention bundles using peer
      tutoring in a resource-limited setting was useful and effectively reduced
      CLABSIs. However, maintaining the reduced CLABSI rate will require further
      strategies.

PMID- 29026534
TI  - Recent advances in hepatic encephalopathy.
AB  - Hepatic encephalopathy describes the array of neurological alterations that occur
      during acute liver failure or chronic liver injury. While key players in the
      pathogenesis of hepatic encephalopathy, such as increases in brain ammonia,
      alterations in neurosteroid levels, and neuroinflammation, have been identified,
      there is still a paucity in our knowledge of the precise pathogenic mechanism.
      This review gives a brief overview of our understanding of the pathogenesis of
      hepatic encephalopathy and then summarizes the significant recent advances made
      in clinical and basic research contributing to our understanding, diagnosis, and
      possible treatment of hepatic encephalopathy. A literature search using the
      PubMed database was conducted in May 2017 using "hepatic encephalopathy" as a
      keyword, and selected manuscripts were limited to those research articles
      published since May 2014. While the authors acknowledge that many significant
      advances have been made in the understanding of hepatic encephalopathy prior to
      May 2014, we have limited the scope of this review to the previous three years
      only.

PMID- 29026537
TI  - Negative effects of long-term feeding of high-grain diets to lactating goats on
      milk fat production and composition by regulating gene expression and DNA
      methylation in the mammary gland.
AB  - BACKGROUND: It is well known that feeding a high concentrate (HC) diet to
      lactating ruminants likely induces subacute ruminal acidosis (SARA) and leads to
      a decrease in milk fat production. However, the effects of feeding a HC diet for
      long periods on milk fatty acids composition and the mechanism behind the decline
      of milk fat still remains poorly understood. The aim of this study was to
      investigate the impact of feeding a HC diet to lactating dairy goats on milk fat
      yield and fatty acids composition with an emphasis on the mechanisms underlying
      the milk fat depression. Seventeen mid-lactating dairy goats were randomly
      allocated to three groups. The control treatment was fed a low-concentrate diet
      (35% concentrate, n = 5, LC) and there were two high-concentrate treatments (65%
      concentrate, HC), one fed a high concentrate diet for a long period (19 wks, n =
      7, HL); one fed a high concentrate diet for a short period of time (4 wk, n = 5,
      HS). Milk fat production and fatty acids profiles were measured. In order to
      investigate the mechanisms underlying the changes in milk fat production and
      composition, the gene expression involved in lipid metabolism and DNA methylation
      in the mammary gland were also analyzed. RESULTS: Milk production was increased
      by feeding the HC diet in the HS and HL groups compared with the LC diet (P <
      0.01), while the percentage of milk fat was lower in the HL (P < 0.05) but not in
      the HS group. The total amount of saturated fatty acids (SFA) in the milk was not
      changed by feeding the HC diet, whereas the levels of unsaturated fatty acids
      (UFA) and monounsaturated fatty acids (MUFA) were markedly decreased in the HL
      group compared with the LC group (P < 0.05). Among these fatty acids, the
      concentrations of C15:0 (P < 0.01), C17:0 (P < 0.01), C17:1 (P < 0.01), C18:1n-9c
      (P < 0.05), C18:3n-3r (P < 0.01) and C20:0 (P < 0.01) were markedly lower in the
      HL group, and the concentrations of C20:0 (P < 0.05) and C18:3n-3r (P < 0.01)
      were lower in the HS group compared with the LC group. However, the
      concentrations of C18:2n-6c (P < 0.05) and C20:4n-6 (P < 0.05) in the milk fat
      were higher in the HS group. Real-time PCR results showed that the mRNA
      expression of the genes involved in milk fat production in the mammary gland was
      generally decreased in the HL and HS groups compared with the LC group. Among
      these genes, ACSL1, ACSS1 & 2, ACACA, FAS, SCD, FADS2, and SREBP1 were down
      regulated in the mammary gland of the HL group (P < 0.05), and the expressions of
      ACSS2, ACACA, and FADS2 mRNA were markedly decreased in the HS goats compared
      with the LC group (P < 0.05). In contrast to the gene expression, the level of
      DNA methylation in the promoter regions of the ACACA and SCD genes was increased
      in the HL group compared with the LC group (P < 0.05). The levels of ACSL1
      protein expression and FAS enzyme activity were also decreased in the mammary
      gland of the HL compared with the LC group (P < 0.05). CONCLUSIONS: Long-term
      feeding of a HC diet to lactating goats induced milk fat depression and FAs
      profile shift with lower MUFAs but higher SFAs. A general down-regulation of the
      gene expression involved in the milk fat production and a higher DNA methylation
      in the mammary gland may contribute to the decrease in milk fat production in
      goats fed a HC diet for long time periods.

PMID- 29026538
TI  - Plasma and cerebrospinal fluid interleukin-1beta during lipopolysaccharide
      induced systemic inflammation in ewes implanted or not with slow-release
      melatonin.
AB  - BACKGROUND: Interleukin-1beta (IL-1beta) is important mediator of inflammatory
      induced suppression of reproductive axis at the hypothalamic level. At the
      beginning of inflammation, the main source of cytokines in the cerebrospinal
      fluid (CSF) is peripheral circulation, while over time, cytokines produced in the
      brain are more important. Melatonin has been shown to decrease pro-inflammatory
      cytokines concentration in the brain. In ewes, melatonin is used to advance the
      onset of a breading season. Little is known about CSF concentration of IL-1beta
      in ewes and its correlation with plasma during inflammation as well as melatonin
      action on the concentration of IL-1beta in blood plasma and the CSF, and brain
      barriers permeability in early stage of lipopolysaccharide (LPS)-induced
      inflammation. METHODS: Systemic inflammation was induced through LPS
      administration in melatonin- and sham-implanted ewes. Blood and CSF samples were
      collected before and after LPS administration and IL-1beta and albumin
      concentration were measured. To assess the functions of brain barriers albumin
      quotient (QAlb) was used. Expression of IL-1beta (Il1B) and its receptor type I
      (Il1r1) and type II (Il1r2) and matrix metalloproteinase (Mmp) 3 and 9 was
      evaluated in the choroid plexus (CP). RESULTS: Before LPS administration, IL
      1beta was on the level of 62.0 +/- 29.7 pg/mL and 66.4 +/- 32.1 pg/mL in plasma
      and 26.2 +/- 5.4 pg/mL and 21.3 +/- 8.7 pg/mL in the CSF in sham- and melatonin
      implanted group, respectively. Following LPS it increased to 159.3 +/- 53.1 pg/mL
      and 197.8 +/- 42.8 pg/mL in plasma and 129.8 +/- 54.2 pg/mL and 139.6 +/- 51.5
      pg/mL in the CSF. No correlations was found between plasma and CSF IL-1beta
      concentration after LPS in both groups. The QAlb calculated before LPS and 6 h
      after was similar in all groups. Melatonin did not affected mRNA expression of
      Il1B, Il1r1 and Il1r2 in the CP. The mRNA expression of Mmp3 and Mmp9 was not
      detected. CONCLUSIONS: The lack of correlation between plasma and CSF IL-1beta
      concentration indicates that at the beginning of inflammation the local synthesis
      of IL-1beta in the CP is an important source of IL-1beta in the CSF. Melatonin
      from slow-release implants does not affect IL-1beta concentration in plasma and
      CSF in early stage of systemic inflammation.

PMID- 29026539
TI  - The regulation of IMF deposition in pectoralis major of fast- and slow- growing
      chickens at hatching.
AB  - BACKGROUND: The lipid from egg yolk is largely consumed in supplying the energy
      for embryonic growth until hatching. The remaining lipid in the yolk sac is
      transported into the hatchling's tissues. The gene expression profiles of fast-
      and slow-growing chickens, Arbor Acres (AA) and Beijing-You (BJY), were
      determined to identify global differentially expressed genes and enriched
      pathways related to lipid metabolism in the pectoralis major at hatching.
      RESULTS: Between these two breeds, the absolute and weight-specific amounts of
      total yolk energy (TYE) and intramuscular fat (IMF) content in pectoralis major
      of fast-growing chickens were significantly higher (P < 0.01, P < 0.01, P < 0.05,
      respectively) than those of the slow-growing breed. IMF content and u-TYE were
      significantly related (r = 0.9047, P < 0.01). Microarray analysis revealed that
      gene transcripts related to lipogenesis, including PPARG, RBP7, LPL, FABP4,
      THRSP, ACACA, ACSS1, DGAT2, and GK, were significantly more abundant in breast
      muscle of fast-growing chickens than in slow-growing chickens. Conversely, the
      abundance of transcripts of genes involved in fatty acid degradation and
      glycometabolism, including ACAT1, ACOX2, ACOX3, CPT1A, CPT2, DAK, APOO, FUT9,
      GCNT1, and B4GALT3, was significantly lower in fast-growing chickens. The results
      further indicated that the PPAR signaling pathway was directly involved in fat
      deposition in pectoralis major, and other upstream pathways (Hedgehog, TGF-beta,
      and cytokine-cytokine receptor interaction signaling pathways) play roles in its
      regulation of the expression of related genes. CONCLUSIONS: Additional energy
      from the yolk sac is transported and deposited as IMF in the pectoralis major of
      chickens at hatching. Genes and pathways related to lipid metabolism (such as
      PPAR, Hedgehog, TGF-beta, and cytokine-cytokine receptor interaction signaling
      pathways) promote the deposition of IMF in the pectoralis major of fast-growing
      chickens compared with those that grow more slowly. These findings provide new
      insights into the molecular mechanisms underlying lipid metabolism and deposition
      in hatchling chickens.

PMID- 29026540
TI  - Energetic-protein supplementation in the last 60 days of gestation improves
      performance of beef cows grazing tropical pastures.
AB  - BACKGROUND: Nutrition is one of the most important factors that affect animal
      performance, and it therefore also impacts on financial results in beef systems.
      In this way, finding the best strategy for feeding supplements is of paramount
      importance. Aiming to evaluate the effect of supplement feeding strategies for
      beef cows in the last third of gestation, two experiments were conducted. In
      Experiment 1, 35 pregnant Nellore cows were assigned to a completely randomized
      design with four treatments: control, which received no supplement;
      supplementation for the last 30 d of gestation (30-d; 3.0 kg/d); supplementation
      for the last 60 d of gestation (60-d; 1.5 kg/d); or supplementation for the last
      90 d of gestation (90-d; 1.0 kg/d). All supplemented treatments received the same
      total amount of supplement throughout the experiment: 90 kg (20% of crude
      protein). A second experiment (Experiment 2) was delineated to evaluate the
      effects of the amounts offered in Experiment 1 on intake and metabolism. Four
      multiparous pregnant Nellore cows were assigned to a 4 * 4 Latin square design,
      with periods of 15 d each. RESULTS: There was a linear effect of the number of
      days of supplementation on calving body weight (BW; P < 0.05) and a quadratic
      effect on BW change from parturition to d 31 post-calving (P < 0.05), with cows
      on the 60-d strategy losing less BW post-calving. No difference was found in
      offspring birth BW (P > 0.10). A significant linear effect on interval from
      parturition to conception (P < 0.05) was observed, with the highest calving to
      conception interval being observed in the 90-d strategy. The level of
      supplementation did not affect forage intake or neutral detergent fiber
      digestibility (P > 0.10). Nitrogen excreted through urine tended to increase
      linearly with the level of supplementation (P < 0.10). CONCLUSION: Providing 1.5
      kg of supplement during the last 60 d of gestation improves cow performance after
      calving, reducing the magnitude of BW lost, and reduces the number of days from
      calving to re-conception in the following breeding season compared to the usually
      recommended period of supplementation of 90 d pre-partum.

PMID- 29026541
TI  - Molecular features that predict the response to antimetabolite chemotherapies.
AB  - BACKGROUND: Antimetabolite chemotherapeutic agents that target cellular
      metabolism are widely used in the clinic and are thought to exert their anti
      cancer effects mainly through non-specific cytotoxic effects. However, patients
      vary dramatically with respect to treatment outcome, and the sources of
      heterogeneity remain largely unknown. METHODS: Here, we introduce a computational
      method for identifying gene expression signatures of response to chemotherapies
      and apply it to human tumors and cancer cell lines. Furthermore, we characterize
      a set of 17 antimetabolite agents in various contexts to investigate determinants
      of sensitivity to these agents. RESULTS: We identify distinct favorable and
      unfavorable metabolic expression signatures for 5-FU and Gemcitabine.
      Importantly, we find that metabolic pathways targeted by each of these
      antimetabolites are specifically enriched in its expression signatures. We
      provide evidence against the common notion about non-specific cytotoxic functions
      of antimetabolite drugs. CONCLUSIONS: This study demonstrates through unbiased
      analyses that the activities of metabolic pathways likely contribute to
      therapeutic response.

PMID- 29026542
TI  - A population-based survey on physical inactivity and leisure time physical
      activity among adults in Chiang Mai, Thailand, 2014.
AB  - BACKGROUND: Reducing physical inactivity among the population is a challenge for
      many nations. Targeting leisure time physical activity (LTPA) may be useful in
      increasing overall physical activity as it is assumed it is associated with a
      higher degree of free choice and personal preference than physical activity at
      work and during travel. The study explored the prevalence of physical inactivity
      and focused on the overall level of energy expenditure and energy level spent
      during leisure time among those who were physically inactive and assessed the
      stages of change for LTPA among those who were physically inactive. METHODS: A
      population-based survey was conducted in 2014 in Chiang Mai, Thailand using a
      stratified two-stage cluster sampling technique. The Global Physical Activity
      Questionnaire (GPAQ) was used to collect the data on physical activity.
      Sufficient levels of physical activity (PA) were defined as >=150 min/week of
      moderate-intensity PA or >=75 min/week of vigorous-intensity PA or >=600
      metabolic equivalent of task (MET)-minutes/week. Weighted analyses were used to
      estimate the prevalence of physical inactivity, the total energy expenditure and
      expenditure during LTPA as well as stages of change among the physically inactive
      population. RESULTS: A total of 1744 people (808 men and 936 women), aged 15 to
      64 years, participated in the study. We estimated that a quarter (26%) of the
      population were physically inactive. Physical inactivity was more commonly found
      among women than men in most age groups. LTPA contributed a small proportion of
      overall PA. On average, physically inactive men spent 132.8 MET-minutes/week and
      inactive women spent 208.2 MET-minutes/week in overall PA which is well below the
      600 MET-minutes/week recommend by the World Health Organization. Around 75% of
      physically inactive people had no intention of engaging in regular LTPA.
      CONCLUSION: About a quarter of the investigative population were physically
      inactive. Most physically inactive members of the population participate in low
      levels of LTPA, but the majority has no intention of increasing PA during leisure
      time. A large-scale health promotion program is needed, and it should focus on an
      approach for the pre-contemplated population.

PMID- 29026543
TI  - From Gardner fibroma diagnosis to constitutional APC mutation detection: a one
      way street.
AB  - We report a young child without a family history of FAP, who promptly underwent
      APC testing after the histological confirmation of a paraspinal GAF that was not
      isolated. Our case report reinforces the suggestion advanced by previous authors
      for an APC analysis in all patients with GAF.

PMID- 29026544
TI  - Central nervous system Tuberculosis in a man from Cambodia with worsening
      headaches.
AB  - Central nervous system (CNS) tuberculosis should be considered in patients from
      endemic nations with worsening neurological symptoms. If imaging reveals possible
      CNS tuberculomas, potentially life-threatening lesions should be excised and
      analyzed. When disease is less severe, other tissues possibly infected should be
      biopsied first for diagnosis to avoid neurosurgery.

PMID- 29026545
TI  - Resuscitative endovascular balloon occlusion of the aorta as an adjunct for
      hemorrhagic shock due to uterine rupture: a case report.
AB  - Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a life
      saving procedure used to control bleeding and maintain blood pressure temporarily
      in traumatic hemorrhagic shock. Uterine rupture and placenta accreta provoke
      uncontrollable massive hemorrhaging. REBOA may be useful for hemodynamic
      stabilization to prevent cardiac arrest in high-risk pregnancy.

PMID- 29026546
TI  - Systemic BCG-osis following intravesical BCG instillation for bladder carcinoma.
AB  - Intravesical instillation of Bacillus Calmette-Guerin (BCG) has been shown to be
      an effective form of immunotherapy for bladder cancer. This case report describes
      a patient who develops systemic BCG-osis following intravesical BCG instillation
      and demonstrates the importance of being aware of more severe complications
      associated with BCG immunotherapy.

PMID- 29026547
TI  - Late onset of unilateral optic disk edema secondary to treatment with imatinib
      mesylate.
AB  - Prompt ophthalmology evaluation and immediate imatinib suspension should be
      suggested at any time of tyrosine kinase inhibitor therapy in patients with
      visual deficit, as it may be a clinical manifestation of optic disk edema, and
      suspension may help in prompt recovery.

PMID- 29026548
TI  - Erythromelanosis follicularis faciei et colli with reticulated hyperpigmentation
      of the extremities.
AB  - Erythromelanosis follicularis faciei et colli (EFFC) is a distinct, rare, and
      underdiagnosed condition of unknown etiology that is characterized by well
      demarcated erythema, hyperpigmentation, and follicular papules. The pigmentation
      is usually on both maxillary, preauricular regions, and the cheeks. We report a
      case of a 12-year-old boy with EFFC that was associated with reticulated
      pigmentation of the extremities.

PMID- 29026549
TI  - Assessment of pathogenesis of infective endocarditis by plasma IgG antibody titer
      test against periodontal bacteria.
AB  - Oral bacteria cause infective endocarditis (IE), so severe periodontitis is
      thought to be high risk for IE. We suggest the identification of high-risk
      patients by an IgG antibody titer test against periodontal bacteria might become
      common screening test.

PMID- 29026550
TI  - Making (mis) sense of asymptomatic marked hypercalcemia in pregnancy.
AB  - We describe a rare case of homozygous inactivating calcium-sensing receptor
      mutation detected during pregnancy and mimicking primary hyperparathyroidism. In
      pregnancy, the differential diagnosis of hypercalcaemia requires a cautious
      approach as physiological changes in calcium homeostasis may mask rare genetic
      conditions.

PMID- 29026551
TI  - Extrinsic pulmonary artery compression mimicking acute pulmonary embolism.
AB  - Right ventricular strain patterns on electrocardiogram such as right axis
      derivation and S1Q3T3 are well known for their diagnostic value in cases of acute
      pulmonary embolism. Nonetheless, these changes are not pathognomonic. We report a
      patient with electrocardiographic evidence of right ventricular strain secondary
      to an unusual etiology.

PMID- 29026552
TI  - The discussion of t(1;17)(p11;q21) translocation in acute promyelocytic leukemia
      patient on molecular remission.
AB  - Some chromosomal aberrations emerging in the course of treatment are probably not
      related to disease progression, but attribute to the germline alteration.
      Therefore, the dynamic genetic tests should be performed during the whole
      treatment process, which is significantly essential for efficacy evaluation and
      treatment decision- making.

PMID- 29026554
TI  - Aortic stent graft placement under extracorporeal membrane oxygenation in severe
      multiple trauma.
AB  - Placement of an aortic stent graft under extracorporeal membrane oxygenation was
      the life-saving procedure in a case of severe head trauma and traumatic aortic
      dissection after injured by a railroad engine. Timely access to neurosurgery,
      heart surgery, and radiology providing minimal invasive interventions increase
      the chances of a favorable outcome.

PMID- 29026555
TI  - Pasireotide and octreotide in the treatment of severe late dumping syndrome.
AB  - Hypoglycemia due to late dumping is a significant problem postoesophagectomy but
      may not always be diagnosed sufficiently early. It can be difficult to treat and
      may severely compromise quality of life. The combination of diazoxide and
      octreotide or more probably pasireotide may transform the patient's life and
      should be considered in all problematic cases.

PMID- 29026553
TI  - Gitelman syndrome: a rare life-threatening case of hypokalemic paralysis
      mimicking Guillain-Barre syndrome during pregnancy and review of the literature.
AB  - In rare cases, patients with Gitelman syndrome may present with hypokalemic
      paralysis mimicking Guillain-Barre syndrome. The severity of resultant symptoms
      may be life-threatening. Controversial drugs such as aldactone, amiloride, and
      eplerenone should be used in this situation despite the lack of safety data.

PMID- 29026556
TI  - Which is the best in carbamazepine overdose?
AB  - Intravenous lipid emulsion treatment is safer, faster, and easier to apply and
      could be a powerful alternative to extracorporeal treatment methods in
      carbamazepine intoxication.

PMID- 29026557
TI  - Aggressive squamous cell carcinoma of the bladder associated with a history of
      large bladder stone - a case report.
AB  - History of large bladder stones suggests a long-standing chronic irritation of
      the bladder, a known risk factor for squamous cell carcinoma. Therefore, in such
      patients, we suggest random biopsies to detect presence of dysplasia or
      malignancy and a follow-up cystoscopy for early detection of a possible tumor.

PMID- 29026558
TI  - Expanded phenotype in a patient with spastic paraplegia 7.
AB  - Hereditary spastic paraplegia is a group of clinically and genetically
      heterogeneous neurodegenerative disorders, often characterized by weakness and
      spasticity in the lower limbs. In our study, we describe a spastic paraplegia
      type 7 patient with an expanded phenotype who was diagnosed after the discovery
      of pathogenic variants in SPG7.

PMID- 29026559
TI  - Verapamil-sensitive atrial tachycardia with a slow conduction zone near the
      noncoronary aortic sinus and His bundle.
AB  - This report presents a verapamil-sensitive atrial tachycardia, mid-atrium septum
      activating the earliest. Concealed entrainment was obtained at noncoronary aortic
      sinus (NCS), where the local activation was delayed compared to mid-septum. The
      tachycardia was successfully ablated at NCS. The entrance of the slow conduction
      zone was located at NCS.

PMID- 29026560
TI  - Uncommon response of cisplatin and etoposide for treatment of advanced medullary
      thyroid carcinoma.
AB  - Systemic treatment of Medullary thyroid carcinoma (MTC) is currently limited to
      the use of a tyrosine kinase inhibitor. Cytotoxic chemotherapy is not routinely
      recommended in the earlier lines of treatment due to the lack of efficacy. We
      describe a patient with locally advanced MTC who had an uncommon response to
      cisplatin and etoposide.

PMID- 29026561
TI  - Primary hypogonadism, partial alopecia, and Mullerian hypoplasia: report of a
      fifth family and review.
AB  - Primary hypogonadism combined with Mullerian hypoplasia and partial alopecia are
      common features of this syndrome, which was reported only in four earlier
      families from areas where consanguineous marriage is prevalent. An autosomal
      recessive pattern of inheritance was suggested earlier and is supported by this
      report.

PMID- 29026562
TI  - Developmental progression of intellectual disability, autism, and epilepsy in a
      child with an IQSEC2 gene mutation.
AB  - The neurodevelopmental progression of a school-aged child with a spontaneous
      IQSEC2 mutation has demonstrated apparent regression of milestones and language.
      Seizures associated with the disorder have been refractory to medical treatment.
      Late treatment of autism in this child has led to improved social skills.

PMID- 29026563
TI  - Methotrexate-induced leukoencephalopathy presenting as stroke in the emergency
      department.
AB  - Methotrexate-induced leukoencephalopathy is to be considered as a potential
      etiology in any patient presenting with stroke-like symptoms after receiving
      methotrexate. One of our cases suggests that the method of administration of the
      methotrexate can be IV or intrathecal and still results in leukoencephalopathy.

PMID- 29026564
TI  - Left main trunk stenting in a case of acute aortic dissection: a case report.
AB  - In cases involving unstable hemodynamics in patients with Stanford type-A acute
      aortic dissection involving left main trunk (LMT) compression, LMT stenting
      without antiplatelet agents may be a good option as a bridge to surgery.

PMID- 29026565
TI  - Supraventricular microreentry in a newborn due to a giant atrial septum aneurysm.
AB  - Supraventricular arrhythmias in neonates are rare and mostly not related to
      structural heart defects. We present the first case of a newborn with a
      supraventricular microreentrant tachycardia possibly associated with an atrial
      septum aneurysm and emphasize the importance of a thorough diagnostic workup
      allowing a fast and adequate therapy.

PMID- 29026566
TI  - Synchronous Hodgkin's lymphoma and seminoma: a rare coexistence and an important
      lesson.
AB  - Synchronous presentation of seminoma and lymphoma is rare but has important
      ramifications for the treatment of both malignancies. Without clinical vigilance,
      this situation may be easily missed, leading to inappropriate management. We
      describe a patient with synchronous seminoma and Hodgkin's lymphoma and discuss
      the implication on his treatment.

PMID- 29026567
TI  - Proactive use of eltrombopag before the onset of clinical bleeding in two
      children with immune thrombocytopenia and lifestyle restrictions.
AB  - Children with immune thrombocytopenia (ITP) are often managed using a watch-and
      wait approach to avoid conventional treatment that may be poorly tolerated.
      However, in some patients, this approach may lead to lifestyle restrictions due
      to risk of injury-related bleeding. Eltrombopag is a well-tolerated new option
      that may help these children.

PMID- 29026568
TI  - A rare case of CD1a-negative Langerhans cell histiocytosis of the central nervous
      system in a child.
AB  - Langerhans cell histiocytosis is a dendritic cell disorder with a wide spectrum
      of severity and presentations. Histopathology typically demonstrates a
      proliferation of Langerhans cells and a lymphohistiocytic inflammatory infiltrate
      with eosinophils. The diagnosis is supported by immunohistochemistry with the
      cell markers S100, CD1a, CD68, and Langerin [Blood, 126, 2015, 26 and N Engl J
      Med, 331, 1994, 154].

PMID- 29026569
TI  - Sudden maternal hypoxemia during elective cesarean section in a woman with
      placenta previa.
AB  - There have been no reports regarding imaging-documented bronchospasm in patients
      with amniotic fluid embolism (AFE). In a woman with scheduled cesarean section
      for placenta previa, transient bronchospasm and pulmonary hypertension were
      documented explaining a sudden drop in SpO2. Mild AFE was the most likely
      diagnosis in this patient.

PMID- 29026570
TI  - Calypso's spell: accidental near-fatal thiacloprid intoxication.
AB  - Acute life-threatening intoxications with insecticides are rare. We report a case
      of accidental near-fatal thiacloprid intoxication with mass spectrometry-based
      analytical confirmation. The initial clinical presentation resembled imminent
      brain death and/or severe postanoxic encephalopathy. Prolonged supportive
      treatment resulted in full recovery underlining intoxication as an important
      differential diagnosis in unclear coma.

PMID- 29026571
TI  - Maxillary molar healing after treatment of an uninstrumented canal with a novel
      root canal procedure: a case report.
AB  - A major cause for endodontic failure is the inability to treat all anatomy.
      Studies report endodontic retreatments contain 42% missed canals. This case
      illustrates dentin preservation of a molar with an uninstrumented mesiobuccal-3
      canal revealed post-GentleWave Procedure. Efficient cleaning and disinfection
      with maintained healing to 18 months is demonstrated.

PMID- 29026572
TI  - Nasopharyngeal carcinoma presenting as an inconspicuous primary lesion with
      extensive cavernous sinus involvement and temporal lobe extension: a case report
      and review of literature.
AB  - Detection of nodal metastasis in the neck or adjacent structures is common in
      nasopharyngeal carcinoma (NPC) when there is frank primary disease. Intracranial
      extension without obvious nasopharyngeal disease is not common. Here, we discuss
      a patient with NPC that presented with extensive intracranial disease with subtle
      findings in the nasopharynx.

PMID- 29026573
TI  - Polycystic pancreatic disease associated with pineal cyst in an adolescent: a
      case report and literature overview.
AB  - Pancreatic polycystosis is one of rare causes of recurrent abdominal pain of
      pancreatic origin in children frequently associated with other organ's cysts
      which are to be searched. Association with pineal cyst is exceptional, and link
      between the two locations is to be elucidated. MRI is highly valuable to
      characterize cysts.

PMID- 29026574
TI  - Complete remission of rare adenocarcinoma of the oropharynx with APCEDEN(r)
      (dendritic cell-based vaccine): a case report.
AB  - APCEDEN (r) is an autologous monocyte-derived dendritic cell-based immunotherapy.
      A 58-year-old man with adenocarcinoma of oropharynx shows complete remission
      after receiving APCEDEN (r) in conjunction with Geftinib validated by reduction
      in size, whereas Gefitinib alone lead to disease progression.

PMID- 29026575
TI  - Cystic fibrosis and Silver-Russell syndrome due to a partial maternal isodisomy
      of chromosome 7.
AB  - If an infant with cystic fibrosis exhibits failure to thrive, despite adequate
      disease management, Silver-Russell syndrome should be considered, given the
      locations of these conditions in the genome. However, an earlier clue to the
      diagnosis is small-for-gestational-age birth.

PMID- 29026576
TI  - Use of granulocyte colony-stimulating factor in the treatment of methimazole
      induced agranulocytosis: a case report.
AB  - A comparison of this case to previously published reports suggests that
      granulocyte colony-stimulating factor may be associated with improved prognosis
      in severe antithyroid drug-induced neutropenia, and that weight-based doses could
      be an appropriate strategy.

PMID- 29026577
TI  - Split high-dose oral levothyroxine treatment as a successful therapy option in
      myxedema coma.
AB  - High-dose intravenous thyroxine (T4) is the preferable treatment for myxedema
      coma. We describe the clinical course of a 69-year-old man who presented with
      myxedema coma and received oral levothyroxine (LT4) therapy (1 mg) in a split
      dose. This suggests split high-dose oral LT4 as a therapeutic option in myxedema
      coma.

PMID- 29026578
TI  - Spontaneous dissection limited to left gastric artery.
AB  - Spontaneous dissection without an aneurysm limited to left gastric artery is
      fairly rare. Physicians should be alert to the possibility of this condition in
      patients with sudden-onset abdominal pain.

PMID- 29026579
TI  - Amlodipine-induced gingival enlargement.
AB  - The three most common classes of medications implicated in drug-induced gum
      enlargement are anticonvulsives, calcineurin inhibitors, and calcium channel
      blockers. Treatment primarily consists of withdrawing the offending agent
      whenever possible, in addition to maintaining good oral hygiene. Gingivectomy or
      flap surgery may be needed in resistant cases.

PMID- 29026580
TI  - 123I-BMIPP single-photon emission computed tomography for diagnosing chest pain
      in patients with nonobstructive coronary angiograms: Takotsubo or vasospasm?
AB  - The decreased 123I-BMIPP uptake, while having normal perfusion, in the
      correspondent coronary artery territory is caused by a delayed metabolic recovery
      after the recovery of perfusion. This phenomenon termed ischemic memory can
      clearly differentiate vasospastic angina from other chest pain syndromes.

PMID- 29026581
TI  - Hemivertebra of the cervical spine: an uncommon background for neck pain,
      cervical scoliosis, and torticollis.
AB  - A 15-year-old female patient presented with neck pain accompanied by cervical
      scoliosis, on the existence of torticollis. Although rare, hemivertebra of the
      cervical spine is a congenital deformation associated with these three clinical
      features.

PMID- 29026582
TI  - Extrarenal pelvis mimicking hydronephrosis: a case for caution.
AB  - Extrarenal pelvis is an anatomical variant that appears as a large hypoechoic
      mass just outside the renal sinus and can be confused with hydronephrosis,
      especially on a point-of-care renal ultrasound. Unlike hydronephrosis, it is not
      associated with dilated calyces, parenchymal thinning, hydroureter, or enlarged
      kidney per se.

PMID- 29026583
TI  - A case of hypersomnia due to bilateral thalamic stroke.
AB  - Bilateral thalamic infarction (BTI) can present as sleep-like coma without focal
      neurological signs which can lead to delay in the diagnosis. Due to the
      diagnostic challenge, treatment is often delayed. The early use of DWI-MRI in
      suspected cases can help in the early diagnosis and treatment.

PMID- 29026584
TI  - Solitary costal plasmacytoma mimicking lung cancer metastasis.
AB  - A clinical diagnosis of metastatic bone tumors is usually based on radiological
      findings without bone biopsy. Plasmacytoma can present as a single osteolytic
      lesion as described in this case. Early bone biopsy should be considered in
      unusual clinical settings for a differential diagnosis of primary bone tumors.

PMID- 29026585
TI  - Plantar keratoderma of Sezary syndrome.
AB  - Sezary syndrome is an extremely rare form of cutaneous T-cell lymphoma. It
      presents suddenly and is associated with a poor prognosis. Clinical recognition
      is crucial for the diagnostic process and initiation of appropriate treatment.
      Plantar keratoderma is usually pathognomonic for Sezary syndrome and clinicians
      should be alerted to its presence.

PMID- 29026586
TI  - Dilemma during ultrasound-guided internal jugular venous catheterization.
AB  - The presence of Internal Jugular Valves can pose a diagnostic and procedural
      challenge during ultrasound-guided cannulation. After ruling out dissection,
      thrombus, or ultrasound artifacts, it can still be accessed and successfully
      cannulated with appropriate precautions including use of Live ultrasound,
      positioning, use of soft-tipped catheters, and minimizing duration of catheter
      placement.

PMID- 29026587
TI  - Biliopancreatic limb obstruction after laparoscopic Roux-en-Y gastric bypass: a
      rare and potentially fatal condition.
AB  - Biliopancreatic limb obstruction after laparoscopic Roux-en-Y gastric bypass is a
      challenging diagnosis as the symptoms are very nonspecific. CT scan is the
      optimal study for evaluation. Early diagnosis and treatment is essential in
      reducing the morbidity and mortality associated with this condition.

PMID- 29026588
TI  - Granulomatosis with polyangiitis can cause periaortitis and pericarditis.
AB  - Granulomatosis with polyangiitis (GPA) is characterized by necrotizing
      granulomatous inflammation usually involving the upper and lower respiratory
      tracts and necrotizing vasculitis predominantly affecting small-sized vessels.
      Although categorized as a small vessel vasculitis, GPA can cause periaortitis and
      pericarditis. Physicians should recognize all categories of vasculitis can affect
      any size arteries.

PMID- 29026589
TI  - A retrospective analysis of biochemical and haematological parameters in patients
      with eating disorders.
AB  - BACKGROUND: The objective of the study was to determine whether levels of
      biochemical and haematological parameters in patients with eating disorders (EDs)
      varied from the general population. Whilst dietary restrictions can lead to
      nutritional deficiencies, specific abnormalities may be relevant to the
      diagnosis, pathogenesis and treatment of EDs. METHODS: With ethics approval and
      informed consent, a retrospective chart audit was conducted of 113 patients with
      EDs at a general practice in Brisbane, Australia. This was analysed first as a
      total group (TG) and then in 4 ED subgroups: Anorexia nervosa (AN), Bulimia
      nervosa (BN), ED Not Otherwise Specified (EDNOS), and AN/BN. Eighteen parameters
      were assessed at or near first presentation: cholesterol, folate, vitamin B12,
      magnesium, manganese, zinc, calcium, potassium, urate, sodium, albumin,
      phosphate, ferritin, vitamin D, white cell count, neutrophils, red cell count and
      platelets. Results were analysed using IBM SPSS 21 and Microsoft Excel 2013 by
      two-tailed, one-sample t-tests (TG and 4 subgroups) and chi-square tests (TG
      only) and compared to the population mean standards. Results for the TG and each
      subgroup individually were then compared with the known reference interval (RI).
      RESULTS: For the total sample, t-tests showed significant differences for all
      parameters (p < 0.05) except cholesterol. Most parameters gave results below
      population levels, but folate, phosphate, albumin, calcium and vitamin B12 were
      above. More patients than expected were below the RI for most parameters in the
      TG and subgroups. CONCLUSIONS: At diagnosis, in patients with EDs, there are
      often significant differences in multiple haematological and biochemical
      parameters. Early identification of these abnormalities may provide additional
      avenues of ED treatment through supplementation and dietary guidance, and may be
      used to reinforce negative impacts on health caused by the ED to the patient,
      their family and their treatment team (general practitioner, dietitian and mental
      health professionals). Study data would support routine measurement of a full
      blood count and electrolytes, phosphate, magnesium, liver function tests,
      ferritin, vitamin B12, red cell folate, vitamin D, manganese and zinc for all
      patients at first presentation with an ED.

PMID- 29026590
TI  - Eosinophilic esophagitis: What can we learn from Crohn's disease?
AB  - Eosinophilic esophagitis (EoE) is an emerging esophageal inflammatory disorder
      affecting children and young adults. As a relatively new disease, EoE is still
      burdened by frequent diagnostic and therapeutic pitfalls in clinical practice.
      This manuscript posits a number of similarities with Crohn's disease, which may
      help optimize EoE patient management. Commonalities include epidemiologic trends
      (Westernized diseases, rising incidence, early-life risk factors), diagnostic
      considerations (symptoms are poor predictors of disease activity, difficulties in
      disease activity assessment) and therapeutic issues (similar natural history and
      therapeutic goals, induction and maintenance phases, combination of drug and
      endoscopic treatment, potential drug interchangeability, long-term unsolved
      issues). Physicians devoted to EoE should learn from the extraordinary
      achievements fulfilled in Crohn's disease: increased disease awareness,
      multidisciplinary specialized clinics, structured childhood and transition
      programs, and an ongoing roadmap for personalized treatments, including genetic
      susceptibility, risk factors for progression, genotype-phenotype correlation,
      drug monitoring and microbial data.

PMID- 29026592
TI  - Yield of prolonged wireless pH monitoring in achalasia patients successfully
      treated with pneumatic dilation.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a long-term complication
      of achalasia treatments. The aim of our study was to evaluate the yield of
      prolonged wireless pH monitoring in patients with successfully treated achalasia
      and its influence on proton pump inhibitor (PPI) use. METHODS: Twenty-five
      patients with achalasia who underwent prolonged wireless pH monitoring after a
      successful treatment with pneumatic dilation were enrolled. pH variables were
      analysed in the first 24 hours of monitoring to determine if tracings were
      indicative of GORD; the same variables were analysed in the following 24-hour
      period in order to obtain a worst-day diagnosis of GORD. PPI therapy before and
      after the test was recorded. RESULTS: Five out of 25 patients had GORD diagnosis
      during the first day of monitoring and four of them had oesophagitis at
      endoscopy. During the following days of monitoring four more patients had a
      diagnosis of GORD. Out of the 25 patients, PPIs were started after the test in
      six asymptomatic GORD-positive ones, whereas prescription of PPIs was stopped
      without detrimental effect on symptoms in three GORD-negative patients.
      CONCLUSIONS: Prolonged wireless pH monitoring is a useful test to be added to
      endoscopy in order to evaluate GORD and to optimise antisecretory treatment in
      successfully treated achalasia patients.

PMID- 29026591
TI  - Irritable bowel syndrome diagnosis and management: A simplified algorithm for
      clinical practice.
AB  - BACKGROUND: Effective management of irritable bowel syndrome (IBS), a common
      functional gastrointestinal disorder, can be challenging for physicians because
      of the lack of simple diagnostic tests and the wide variety of treatment
      approaches available. OBJECTIVE: The objective of this article is to outline a
      simple algorithm for day-to-day clinical practice to help physicians navigate key
      stages to reaching a positive IBS diagnosis and guidance on how to prioritise the
      use of specific management strategies. METHODS: This algorithm was based on the
      opinion of an expert panel evaluating current evidence. RESULTS: The key
      principles forming the foundation of this evidence-supported algorithm are:
      confidently naming and explaining an IBS diagnosis for the patient, followed by
      assessment of key patient characteristics likely to influence the choice of
      therapy, such as predominant symptoms, and exploring the patient agenda and
      preferences. Consultation should always include education and reassurance with an
      explanatory model of IBS tailored to the patient. Individualised lifestyle
      changes, dietary modifications, pharmacological therapies, psychological
      strategies or a combination of interventions may be used to optimise treatment
      for each patient. CONCLUSION: The simple visual tools developed here navigate the
      key stages to reaching a positive diagnosis of IBS, and provide a stepwise
      approach to patient-centred management targeted towards the most bothersome
      symptoms. Establishing a strong patient-physician relationship is central to all
      stages of the patient journey from diagnosis to effective management.

PMID- 29026593
TI  - Antibiotic resistance and gyrA mutation affect the efficacy of 10-day
      sitafloxacin-metronidazole-esomeprazole therapy for Helicobacter pylori in
      penicillin allergic patients.
AB  - BACKGROUND AND AIM: Helicobacter pylori (H. pylori) eradication regimen has not
      been standardized for patients with penicillin allergy. We investigated the
      association between the efficacy of a 10-day sitafloxacin, metronidazole, and
      esomeprazole triple regimen and antibiotic resistance, in patients with
      penicillin allergy. METHODS: Penicillin-allergic patients infected with H. pylori
      were enrolled between March 2014 and November 2015. The minimum inhibitory
      concentrations (MICs) of sitafloxacin and metronidazole, and the gyrA mutation
      status of the H. pylori strains were determined before treatment. The cut-off
      points for antimicrobial resistance were defined as 8.0 ug/ml for metronidazole
      and 0.12 ug/ml for sitafloxacin. The patients received the triple therapy (20 mg
      esomeprazole, bid; 250 mg metronidazole, bid; and 100 mg sitafloxacin, bid) for
      10 days. Successful eradication was evaluated using the [13C] urea breath test or
      the H. pylori stool antigen test. RESULTS: Fifty-seven patients were analyzed,
      and the overall eradication rate was 89.5%. The eradication rate in cases of
      double antibiotic resistance to metronidazole and sitafloxacin was 40.0%, whereas
      for other combinations of resistance, this was above 90.0%. Finally, the
      eradication rate of gyrA mutation-negative strains was 96.2%, whereas for gyrA
      mutation-positive strains, it was 83.9%. Adverse events were reported in 31.6% of
      cases, all of which were mild and tolerable. CONCLUSION: Ten days of sitafloxacin
      and metronidazole triple therapy was safe and highly effective in eradicating H.
      pylori in penicillin-allergic patients. Double resistance to metronidazole and
      sitafloxacin was an important predicting factor for eradication failure. However,
      10 days of the sitafloxacin and metronidazole triple therapy was highly effective
      if the strain was susceptible to either sitafloxacin or metronidazole.

PMID- 29026594
TI  - Subtypes of chronic gastritis in patients with celiac disease before and after
      gluten-free diet.
AB  - BACKGROUND: Celiac disease (CD) often manifests with dyspeptic symptoms and
      chronic gastritis is a common finding. AIM: To evaluate the frequency of
      lymphocytic gastritis (LG), chronic active gastritis (CAG), and chronic inactive
      gastritis (CIG) in patients with CD, before and after gluten-free diet (GFD).
      METHODS: A five-year prospective study including all consecutive patients with a
      new diagnosis of CD was conducted. Gastric and duodenal biopsy specimens taken
      both at the time of the CD diagnosis and at the first endoscopic control after 18
      24 months on GFD were evaluated. RESULTS: 213 patients with CD were enrolled. At
      the time of the diagnosis, 42 patients (19.7%) showed normal gastric mucosa, 34
      (15.9%) LG, 67 (31.5%) CAG, and 70 (32.9%) CIG. Out of the 34 patients with LG,
      all were Helicobacter pylori negative and the majority of them showed an
      improvement both of gastritis (94.1%) and duodenal lesions (82.3%) after GFD. GFD
      did not show significant effects on CAG and CIG. CONCLUSIONS: LG is present in
      16% of CD patients, it is not associated with H. pylori infection, and it
      improves after GFD. Both CAG and CIG are also frequently associated with CD, but
      fail to respond to a GFD.

PMID- 29026595
TI  - Time trend occurrence of duodenal intraepithelial lymphocytosis and celiac
      disease in an open access endoscopic population.
AB  - BACKGROUND: Duodenal intraepithelial lymphocytosis (DIL) is a histological
      finding characterized by the increase of intraepithelial CD3T-lymphocytes over
      the normal value without villous atrophy, mostly associated to coeliac disease
      (CD), Helicobacter pylori (Hp) gastritis and autoimmune diseases. OBJECTIVE: To
      assess the occurrence of DIL, CD and Hp gastritis in an endoscopic population
      over a 13 year period. METHODS: From 2003 to 2015 we included adult patients who
      consecutively underwent oesophago-gastro-duodenoscopy (OGD) with duodenal
      biopsies assessing the overall and annual occurrence of DIL and CD and the
      prevalence of Hp gastritis. RESULTS: 160 (2.3%) patients with DIL and 275 (3.9%)
      with CD were detected among 7001 patients. CD occurrence was higher from 2003 to
      2011, while since 2012 DIL occurrence gradually increased significantly compared
      to CD (p = 0.03). DIL patients were more frequently female (p = 0.0006) and
      underwent OGD more frequently for dyspepsia (p = 0.002) and for indications not
      related to gastrointestinal symptoms than CD patients (p = 0.0003). Hp gastritis
      occurred similarly in CD and DIL patients but the latter had higher frequency of
      atrophic body gastritis (p = 0.005). CONCLUSIONS: DIL is a condition increasing
      in the general endoscopic population mainly diagnosed by chance. Concomitant
      gastric histological evaluation is able in one third of DIL patients to identify
      associated possible causes of DIL, such as Hp and atrophic gastritis.

PMID- 29026596
TI  - Flow cytometry of duodenal intraepithelial lymphocytes improves diagnosis of
      celiac disease in difficult cases.
AB  - BACKGROUND: Diagnosis of celiac disease is difficult when the combined results of
      serology and histology are inconclusive. Studies using flow cytometry of
      intraepithelial lymphocytes (IELs) have found that celiac patients have increased
      numbers of gammadelta IELs, along with a decrease in CD3-CD103 + IELs. OBJECTIVE:
      The objective of this article is to assess the role of flow cytometric analysis
      of IELs in the diagnosis of celiac disease in difficult cases. METHODS: A total
      of 312 patients with suspicion of celiac disease were included in the study.
      Duodenal biopsy samples were used for histological assessment and for flow
      cytometric analysis of IELs. RESULTS: In 46 out of 312 cases (14.7%) the
      combination of serology and histology did not allow the confirmation or exclusion
      of celiac disease. HLA typing had been performed in 42 of these difficult cases.
      Taking into account HLA typing and the response to a gluten-free diet, celiac
      disease was excluded in 30 of these cases and confirmed in the remaining 12. Flow
      cytometric analysis of IELs allowed a correct diagnosis in 39 out of 42 difficult
      cases (92.8%) and had a sensitivity of 91.7% (95% CI: 61.5% to 99.8%) and a
      specificity of 93.3% (95% CI: 77.9% to 99.2%) for the diagnosis of celiac disease
      in this setting. CONCLUSION: Flow cytometric analysis of IELs is useful for the
      diagnosis of celiac disease in difficult cases.

PMID- 29026597
TI  - Endoscopic approach for management of biliary strictures in liver transplant
      recipients: A systematic review and meta-analysis.
AB  - : The most common biliary complication after liver transplantation is anastomotic
      stricture (AS) and it can occur isolated or in combination with other
      complications. Liver graft from a cadaveric donor or a living donor has an
      influence on the incidence of biliary strictures as well as on the response to
      endoscopic treatment. Endoscopic treatment using balloon dilation and insertion
      of biliary stents by endoscopic retrograde cholangiopancreatography (ERCP) is the
      initial approach to these complications. AIM: The aim of this article is to
      compare different endoscopic techniques to treat post-liver transplantation
      biliary strictures. METHODS: The search was carried out on MEDLINE, EMBASE,
      Scielo-LILACS and Cochrane Library databases through June 2015. A total of 1100
      articles were retrieved. Ten clinical trials were analyzed, and seven were
      included in the meta-analysis. CONCLUSIONS: The endoscopic treatment of AS was
      equally effective when compared the use of fully covered self-expandable metal
      stents (FCSEMS) vs. plastic stents, but the use of FCSEMS was associated with a
      lower complication risk. The treatment of AS with balloon dilation or balloon
      dilation associated with plastic stents presented similar results. Deceased donor
      liver transplantation reduced the risk of biliary stenosis and the endoscopic
      treatment in these patients was more effective when compared with Living donor
      liver transplantation.

PMID- 29026598
TI  - Endoscopic ultrasound-guided fine needle aspiration of pancreatic lesions with 22
      versus 25 Gauge needles: A meta-analysis.
AB  - BACKGROUND: Robust data in favour of a clear superiority of 22 versus 25 Gauge
      needles for endoscopic ultrasound-guided fine needle aspiration are still
      lacking. OBJECTIVE: We aimed to compare the diagnostic sensitivity, specificity
      and safety of these two needles for endoscopic ultrasound-guided fine needle
      aspiration of solid pancreatic lesions. METHODS: A computerized bibliographic
      search was restricted to randomized controlled trials only. Pooled effects were
      calculated using a random-effects model and expressed in terms of risk ratio and
      95% confidence interval. RESULTS: We analysed seven trials with 689 patients and
      732 lesions (295 sampled with 22 Gauge needle, 309 with 25 Gauge needle, and 128
      with both needles). A non-significant superiority of 25 Gauge in terms of pooled
      sensitivity (risk ratio: 0.93, 0.91-0.95 versus 0.89, 0.85-0.94 of 22 Gauge
      needle; p = 0.13) and no difference in terms of specificity (1.00, 0.98-1.00 in
      both groups; p = 0.85) were observed. Sample adequacy was similar between the two
      devices (risk ratio: 1.03, 0.99-1.06; p = 0.15). Very few adverse events were
      observed and did not impact on patient outcomes. CONCLUSION: Our meta-analysis
      reveals non-superiority of 25 Gauge over 22 Gauge; hence no definitive
      recommendations over the use of one particular device can be made.

PMID- 29026600
TI  - Effect of prophylactic clipping in colorectal endoscopic resection: A meta
      analysis of randomized controlled studies.
AB  - BACKGROUND AND AIM: The efficacy of clipping for preventing delayed bleeding
      after colorectal endoscopic resection is still controversial. To assess the
      efficacy of prophylactic clipping, we conducted a meta-analysis of randomized
      controlled trials. METHODS: We searched PubMed, the Cochrane library, and the
      Igaku-chuo-zasshi database for randomized trials eligible for inclusion in our
      meta-analysis. We identified seven eligible randomized trials from the database
      search, and compared the effect of clipping versus non-clipping with respect to
      delayed bleeding and perforation. Data from eligible studies were combined to
      calculate pooled odds ratios (ORs). RESULTS: Postoperative bleeding was observed
      in 41 of 1526 cases (2.7%) without clipping and in 32 of 1533 cases (2.1%) with
      clipping (OR 0.76, 95% CI: 0.39-1.47, p = 0.414). There was no significant
      heterogeneity among the trial results (I-Square = 26.7%, p = 0.22). In the
      subgroup analysis based on small tumor size (<20 mm) and large tumor size (>=20
      mm), there were no significant differences. Compared with non-clipping, the
      pooled OR of developing perforation with clipping was 1.00 (95% CI: 0.14-7.25),
      indicating no significant difference between the two groups. CONCLUSIONS:
      Prophylactic clipping did not decrease the occurrence of delayed bleeding after
      colorectal endoscopic resection. Clipping could be of interest in patients with a
      high risk of bleeding (anticoagulation) or large lesions, but with the available
      trials data to prove this are scarce.

PMID- 29026599
TI  - Comparison of pancreatic histology specimens obtained by EUS 19G versus 22G core
      biopsy needles: A prospective multicentre study among experienced pathologists.
AB  - BACKGROUND AND AIM: Scanty data about inter-observer agreement (IOA) among
      pathologists in the evaluation of pancreatic samples acquired with EUS histology
      needle are available. The aim of this study was to determine IOA on adequacy of
      pancreatic histology specimens obtained with a 22G needle by a panel of
      experienced pathologist, in comparison with the 19G needle. METHODS: This
      multicentre prospective study involved 73 pancreatic specimens prepared using
      histology needles of different calibres. Five pathologists independently reviewed
      all the samples, assessing the presence of a core, specimen adequacy and the
      possibility to perform additional analyses. IOA determined by Fleiss' Kappa
      statistic was used as the primary outcome measure. Secondary outcome was to
      compare 22G versus 19G needle results. RESULTS: A core was present in 57% of
      pancreatic specimens obtained by 22G needle. The specimens were considered
      adequate in 72% of cases, with poor agreement among pathologists (p = 0.02,
      Fleiss' kappa = 0.26). The possibility to perform further analyses was rated as
      'positive' in 66% of cases without significant difference among observers (p =
      0.80). When comparing the results, the presence of a core and the adequacy of
      tissue slides were significantly better for the 19G needle (57% vs. 84% p =
      0.002; 72% vs. 83% p = 0.004, respectively). Reproducibility in the assessment of
      pancreatic sample adequacy was significantly better with the 19G needle (kappa =
      0.26 for 22G samples vs. kappa = 0.81 for 19G samples). CONCLUSIONS: Our results
      suggest that histology sampling of pancreatic masses should be performed with a
      19G histology needle, since is able to provide a core in the majority of cases,
      with 83% of adequate specimens and excellent results in term of reproducibility
      among pathologists.

PMID- 29026601
TI  - Complications, effectiveness, and long term follow-up of fecal microbiota
      transfer by nasoduodenal tube for treatment of recurrent Clostridium difficile
      infection.
AB  - BACKGROUND: Fecal microbiota transfer (FMT) is an effective treatment for
      recurrent Clostridium difficile infection (CDI), but data on procedure-related
      complications and long-term outcome are scarce. METHODS: All patients treated
      with FMT for recurrent CDI at the Academic Medical Center between July 2010 and
      January 2016 were included. FMT was performed according to the FECAL trial
      protocol: administration of fresh donor feces (related or unrelated donor)
      through a duodenal tube after pre-treatment with vancomycin and bowel lavage. We
      collected information on FMT-related complications, recurrent CDI, and short- and
      long-term adverse events by telephone interviews using a structured questionnaire
      at three months after FMT, and at the time of data collection of this study.
      RESULTS: In total, 39 patients were treated with FMT. The primary cure rate (no
      recurrence <=8 weeks after one infusion with donor feces) was 82% (32 of 39
      patients). Of the seven patients with recurrent CDI after FMT, four were cured by
      antibiotic therapy alone (fidaxomicin in three patients, metronidazole in one
      patient) and three by repeat FMT. Peri-procedural complications occurred in five
      patients, comprising fecal regurgitation or vomiting. One patient died one week
      post-FMT due to pneumonia; a causal relation with FMT could not be excluded. The
      follow-up period ranged between 3 and 68 months. No long-term side effects were
      reported. CONCLUSIONS: Our data underline the efficacy of FMT as treatment for
      recurrent CDI. Importantly, it is possible to cure post-FMT recurrences with
      antibiotic therapy alone. Peri-procedural complications do occur and should be
      closely monitored to help identify high-risk patients. To minimize the risk of
      complications, all FMT candidates should be evaluated to assess the most ideal
      delivery method.

PMID- 29026602
TI  - Re-phrasing the question: A simple tool for evaluation of adherence to therapy in
      patients with inflammatory bowel disease.
AB  - BACKGROUND: Non-adherence to medication in patients with inflammatory bowel
      disease (IBD) is a challenging problem which is often overlooked or under
      estimated by the physician or denied by the patient. We aimed to examine if re
      phrasing the wording of the question used by the physician could help in
      revealing more patients who are non-adherent, and for whom appropriate counseling
      may be instituted. METHODS: A cross-sectional questionnaire-based study of IBD
      patients treated in a tertiary center was conducted. Patients received a
      questionnaire detailing their treatments and disease course, as well as their
      perceptions about disease. Two forms of questions about adherence were
      deliberately placed in two separate parts of the questionnaire: One was 'are you
      taking your medications regularly as prescribed?' (Standard question), and the
      second, more emphatic question, was 'how often does it happen that you miss a
      drug dosing?' (Re-phrased question). The rate of non-adherence disclosed by each
      of these questions was compared. Sensitivity, specificity and predicative values
      were computed for each question against the conventional definition of non
      adherence as taking of less than 80% of prescribed medication doses disclosed by
      any of the methods. Predictors of non-compliance and of denying non-compliance
      were also explored. RESULTS: Overall, 165 patients were included (49% female,
      mean age 33.7 +/- 12.7 SD, median age 30 years, 29.6% with ulcerative colitis,
      62.4% with Crohn's disease). Upon questioning, 50 (30.3%) of the patients
      admitted to non-adherence in the last month when asked by the emphatic re-phrased
      question format, compared with only 10 patients (6%) reporting non-adherence when
      asked directly by the standard question (OR 7.4, 95%CI 3.6-15.2, p < 0.001).
      Thus, a 'Do you take your medicine regularly' question format disclosed only 20%
      of genuinely non-compliant patients and had 16% sensitivity and 98.2% specificity
      for revealing non-adherence (PPV 80%, NPV 72.9%) compared with the reference re
      phrased question. The leading cause for non-adherence was skepticism about drug
      efficacy or safety (20.5%), followed by vacation or weekend (15%), problems with
      prescription or pharmacy (13.5%) and forgetfulness (10%). No single demographic
      or clinical factor correlated with non-adherence. The only factor which
      correlated with higher probability for non-adherence was biological and
      combination treatment. CONCLUSION: Non-compliance with treatment is much more
      common than patients admit. Asking patients how often does it happen that they
      miss a drug dosing is a simple, practical tool which performs significantly
      better in disclosing non-adherence compared with asking patients if they take
      their medication as they should.

PMID- 29026605
TI  - UEG Week 2018 Vienna: Topics and highlights.

PMID- 29026603
TI  - Downregulation of mucosal mast cell activation and immune response in diarrhoea
      irritable bowel syndrome by oral disodium cromoglycate: A pilot study.
AB  - BACKGROUND AND GOAL: Diarrhoea-predominant irritable bowel syndrome (IBS-D)
      exhibits intestinal innate immune and mucosal mast cell (MC) activation. MC
      stabilisers have been shown to improve IBS symptoms but the mechanism is unclear.
      Our primary aim was to investigate the effect of oral disodium cromoglycate
      (DSCG) on jejunal MC activation and specific innate immune signalling pathways in
      IBS-D, and secondarily, its potential clinical benefit. STUDY: Mucosal MC
      activation (by ultrastructural changes, tryptase release and gene expression) and
      innate immune signalling (by protein and gene expression) were quantified in
      jejunal biopsies from healthy (HS; n = 16) and IBS-D subjects after six months of
      either treatment with DSCG (600 mg/day, IBS-D-DSCG group; n = 18) or without
      treatment (IBS-D-NT group; n = 25). All IBS-D patients recorded abdominal pain
      and bowel habits at baseline and in the last 10 days prior to jejunal sampling.
      RESULTS: IBS-D-NT exhibited significant MC activation and over-expression of
      immune-related genes as compared to HS, whereas in IBS-D-DSCG MC activity and
      gene expression were similar to HS. Furthermore, DSCG significantly reduced
      abdominal pain and improved stool consistency. CONCLUSION: Oral DSCG modulates
      mucosal immune activity and improves gut symptoms in IBS-D patients. Future
      placebo-controlled clinical trials are needed for confirmation of clinical
      benefit of DSCG for IBS-D.

PMID- 29026604
TI  - Transglucosidase improves the bowel movements in type 2 diabetes mellitus
      patients: A preliminary randomized double-blind, placebo-controlled study.
AB  - BACKGROUND: Recent studies have highlighted the relationship between gut
      microbiota and bowel movements. OBJECTIVE: We aimed to evaluate transglucosidase
      treatment efficacy for bowel movements in patients with type 2 diabetes mellitus
      and to clarify the relationship between bowel movements, dietary habits, gut
      microbiota and fecal short-chain fatty acids. METHODS: In this randomized double
      blind, placebo-controlled study, 66 patients received placebo or transglucosidase
      (300 or 900 mg/day) orally, for 12 weeks. Fecal bacterial communities and short
      chain fatty acids were analyzed before and after the treatment. RESULTS:
      Transglucosidase treatment significantly (p < 0.05) affected fecal microbiota
      (Prevotella spp., Bacteroides spp., Bifidobacterium spp., and Clostridium
      subcluster XIVa) and fecal short-chain fatty acid (acetate, valerate, succinate
      and lactate) content. Clostridium cluster IV, Clostridium subcluster XIVa,
      Clostridium cluster XVIII and fecal pH increased significantly and order
      Lactobacillales decreased in patients with bowel movement disorder compared with
      controls. Transglucosidase treatment significantly improved bowel movements
      compared with placebo treatment (46.2%, 95% confidence interval: 19.2-74.9% vs.
      0%, 95% confidence interval: 0-33.6%, p < 0.05). This effect was not observed in
      patients without bowel movement disorder. CONCLUSION: Patients with bowel
      movement disorder suffer from gut dysbiosis. Transglucosidase treatment
      alleviates bowel movement disorder symptoms in type 2 diabetes mellitus patients
      by increasing fecal acetate level.

PMID- 29026606
TI  - How to start a Young GI Section in your country - A cookbook.

PMID- 29026607
TI  - Wheezing and dyspnoea caused by aberrant left innominate artery.
AB  - We present a rare case of a branching anomaly of the aortic arch that resulted in
      wheezing and dyspnoea. The patient was a 60-year-old male with severe wheezing
      from babyhood, originally diagnosed with severe bronchial asthma. On
      auscultation, the inspiratory and expiratory wheezes appeared when the patient
      leaned forward. He also had difficulty in swallowing solid mass. Tests for airway
      reversibility and hyperresponsiveness were negative, and asthma treatment was
      ineffective. He had a right aortic arch. A barium oesophagogram and endoscopic
      examination indicated narrowing of the oesophagus from behind. Three-dimensional
      reconstruction of enhanced chest CT images indicated a right aortic arch and an
      aberrant enlarged left innominate artery, which compressed and narrowed the
      oesophagus and trachea from behind. Although the patient had been diagnosed with
      intractable bronchial asthma, his symptoms were more likely caused by this
      mechanical narrowing as wheezing and dyspnoea disappeared completely after total
      aortic arch replacement operation.

PMID- 29026608
TI  - Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia diagnosed by
      tranbronchoscopic cryoprobe biopsy technique.
AB  - Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) remains a
      poorly understood clinical entity. It is currently classified as a premalignant
      condition by the World Health Organization (WHO). Symptoms are similar to those
      associated with obstructive lung disease, including breathlessness and cough. The
      presentation is often initially ascribed to other diseases such as asthma or
      chronic obstructive pulmonary disease. Here, we present what we believe is the
      first described case of DIPNECH diagnosed by transbronchoscopic cryoprobe biopsy.
      The patient presented with chronic cough, dyspnoea, pulmonary function tests
      consistent with obstruction, and a computed tomography (CT) scan of chest with
      multiple nodules. The patient went on to have transbronchoscopic cryoprobe
      biopsies of the lung, which confirmed the diagnosis of DIPNECH.

PMID- 29026609
TI  - Ketosis-prone diabetes and SLE co-presenting in an African lady with previous
      gestational diabetes.
AB  - : We describe the case of an African woman who was diagnosed with ketosis-prone
      diabetes with diabetes-associated autoantibodies, after being admitted for
      diabetic ketoacidosis (DKA) precipitated by her first presentation of systemic
      lupus erythematosus (SLE). She had a seven-year history of recurrent gestational
      diabetes (GDM) not requiring insulin therapy, with return to normoglycaemia after
      each pregnancy. This might have suggested that she had now developed type 2
      diabetes (T2D). However, the diagnosis of SLE prompted testing for an autoimmune
      aetiology for the diabetes, and she was found to have a very high titre of GAD
      antibodies. Typical type 1 diabetes (T1D) was thought unlikely due to the long
      preceding history of GDM. Latent autoimmune diabetes of adults (LADA) was
      considered, but ruled out as she required insulin therapy from diagnosis. The
      challenge of identifying the type of diabetes when clinical features overlap the
      various diabetes categories is discussed. This is the first report of autoimmune
      ketosis-prone diabetes (KPD) presenting with new onset of SLE. LEARNING POINTS:
      DKA may be the first presentation of a multi-system condition and a precipitating
      cause should always be sought, particularly in women with a history of GDM or
      suspected T2D.All women with GDM should undergo repeat glucose tolerance testing
      postpartum to exclude frank diabetes, even when post-delivery capillary blood
      glucose (CBG) tests are normal. They should also be advised to continue CBG
      monitoring during acute illness in case of new onset diabetes.KPD comprises a
      spectrum of diabetes syndromes that present with DKA, but subsequently have a
      variable course depending on the presence or absence of beta cell failure and/or
      diabetes autoantibodies.KPD should be considered in a patient with presumed T2D
      presenting with DKA, especially if there is a personal or family history of
      autoimmune diabetes.LADA should be suspected in adults presumed to have T2D, who
      do not require insulin therapy for at least six months after diagnosis and have
      anti-GAD antibodies.Patients with autoimmune diabetes have an increased risk of
      other autoimmune diseases and screening for thyroid, parietal cell, coeliac and
      antinuclear antibodies should be considered.

PMID- 29026610
TI  - Selective blood sampling for FGF-23 in tumor-induced osteomalacia.
AB  - : Tumor-induced osteomalacia (TIO) is caused by the hormone fibroblast growth
      factor 23 (FGF-23). It is mainly produced in the tissue of mesenchymal tumors.
      Patients with TIO frequently suffer from a chronic decompensated pain syndrome
      and/or muscle weakness with postural deformity. Despite the severity of the
      disease, the diagnosis is frequently established late. In some cases, it takes
      several years to establish the condition. This case report concerning a 68-year
      old woman demonstrates the selective blood sampling for FGF-23 as path-breaking
      diagnostics to confirm the diagnosis of a neuroendocrine tumor. LEARNING POINTS:
      Tumor-induced osteomalacia is a rare condition compared to other paraneoplastic
      syndromes.It causes complex symptoms such as progressive reduction of physical
      capacity, exhaustion, fatigue, a decompensated pain syndrome of the
      musculoskeletal system and fractures of several bones.Elevated serum levels of
      FGF-23 implicate massive phosphate elimination and resulting hypophosphatemia.The
      diagnosis is often established over a period of several years because the
      localization of small FGF-23-producing tumors is complicated.It is the
      combination of MRI and selective blood sampling for FGF-23 which permits reliable
      identification of tumors causing TIO and leads to accurate localization.In a
      patient with generalized pain and reduced physical capacity, osteological
      parameters such as phosphate, 25-OH vitamin D3 and 1,25-(OH)2D3, as well as bone
      specific alkaline phosphatase levels in serum should be determined.
      Hypophosphatemia should always lead to further diagnostic investigations aiming
      at the detection of an FGF-23-producing tumor.

PMID- 29026611
TI  - Branded prescription drug spending: a framework to evaluate policy options.
AB  - BACKGROUND: High drug spending is a concern for policy makers due to limits on
      access for patients. Numerous policies have been proposed to address high drug
      spending. The existence of multifarious proposals makes it difficult for policy
      makers to consider all the alternatives. We developed an approach to select the
      most viable options to present to policy makers. METHODS: We identified 41
      different proposals in the peer-reviewed literature to reduce the level of
      spending or change the incentives for branded prescription drugs; ten of which we
      identified as promising proposals. Based on criterion used to assess various
      legislative proposals regarding branded pharmaceuticals we developed a framework
      to evaluate the ten promising proposals. We then used a modified Delphi technique
      to iteratively evaluate these ten proposals starting with the initial criterion.
      During each iteration, five researchers independently evaluated the ten policies
      based on available criterion and assessed how to modify the criterion to achieve
      consensus on what attributes the criterion were intended to measure. We highlight
      areas of disagreement to show where modifications to existing criterion are
      needed. RESULTS: We found general agreement for most policy-criterion
      combinations after three iterations. Areas with the greatest remaining
      disagreement include possible unintended consequences, the concept of value
      implied by many of the policies, and secondary effects by the pharmaceutical
      industry, insurers, and the FDA. CONCLUSIONS: Our analysis provides an approach
      that can be applied to evaluate policy proposals. It also suggests factors that
      policy analysts and researchers should consider when they propose policy options
      and where additional research is needed to assess policy impacts. Developing an
      objective approach to compare alternatives may facilitate the adoption of
      policies for branded prescription drugs in the U.S. by allowing policy makers to
      focus on the most viable options.

PMID- 29026612
TI  - Estimations of the lethal and exposure doses for representative methanol symptoms
      in humans.
AB  - BACKGROUND: The aim of this review was to estimate the lethal and exposure doses
      of a representative symptom (blindness) of methanol exposure in humans by
      reviewing data from previous articles. METHODS: Available articles published from
      1970 to 2016 that investigated the dose-response relationship for methanol
      exposure (i.e., the exposure concentration and the biological markers/clinical
      symptoms) were evaluated; the MEDLINE and RISS (Korean search engine) databases
      were searched. The available data from these articles were carefully selected to
      estimate the range and median of a lethal human dose. The regression equation and
      correlation coefficient (between the exposure level and urinary methanol
      concentration as a biological exposure marker) were assumed from the previous
      data. RESULTS: The lethal human dose of pure methanol was estimated at 15.8-474
      g/person as a range and as 56.2 g/person as the median. The dose-response
      relationship between methanol vapor in ambient air and urinary methanol
      concentrations was thought to be correlated. An oral intake of 3.16-11.85
      g/person of pure methanol could cause blindness. The lethal dose from respiratory
      intake was reported to be 4000-13,000 mg/l. The initial concentration of optic
      neuritis and blindness were shown to be 228.5 and 1103 mg/l, respectively, for a
      12-h exposure. CONCLUSION: The concentration of biological exposure indices and
      clinical symptoms for methanol exposure might have a dose-response relationship
      according to previous articles. Even a low dose of pure methanol through oral or
      respiratory exposure might be lethal or result in blindness as a clinical
      symptom.

PMID- 29026613
TI  - A case of generalized argyria presenting with muscle weakness.
AB  - BACKGROUND: Argyria is a rare irreversible cutaneous pigmentation disorder caused
      by prolonged exposure to silver. Herein, we report a case of generalized argyria
      that developed after chronic ingestion of soluble silver-nano particles and
      presented with muscle weakness. CASE PRESENTATION: A 74-year-old woman visited
      our emergency room, complaining of fever and mental deterioration. She was
      diagnosed with acute pyelonephritis and recovered after antibiotic therapy. At
      presentation, diffuse slate gray-bluish pigmented patches were noticed on her
      face and nails. Two months prior to visiting our hospital, she was diagnosed with
      inflammatory myopathy and given steroid therapy at another hospital. We performed
      a nerve conduction study that revealed polyneuropathy. In skin biopsies from
      pigmented areas of the forehead and nose, the histopathologic results showed
      brown-black granules in basement membranes of sweat gland epithelia, which are
      diagnostic findings of argyria. We reviewed pathology slides obtained from the
      left thigh muscles and found markedly degenerated myofibers with disorganization
      of myofibrils without inflammatory reactions, consistent with unspecified
      myopathy, rather than inflammatory myopathy. The patient was diagnosed with
      generalized argyria with polyneuropathy and myopathy and transferred to a
      rehabilitation institution after being tapered off of steroids. CONCLUSIONS:
      Clinicians should be aware of clinical manifestations of argyria and consider it
      in differential diagnosis when they examine patients who present with skin
      pigmentation and muscle weakness.

PMID- 29026614
TI  - The association between perceived discriminations and well-being in Korean
      employed workers: the 4th Korean working conditions survey.
AB  - BACKGROUND: Around the globe, discrimination has emerged as a social issue
      requiring serious consideration. From the perspective of public health, the
      impact of discrimination on the health of affected individuals is a subject of
      great importance. On the other hand, subjective well-being is a key indicator of
      an individual's physical, mental, and social health. The present study aims to
      analyze the relationship between Korean employed workers' subjective health and
      their exposure to perceived discrimination. METHODS: The Fourth Korean Working
      Conditions Survey (KWCS, 2014) was conducted on a representative sample of the
      economically active population aged 15 years or older, who were either employees
      or self-employed at the time of interview. After removing inconsistent data,
      32,984 employed workers were examined in this study. The data included general
      and occupational characteristics, perceived discrimination, and well-being. Well
      being was measured through the WHO-Five index (1998 version). Multiple logistic
      regression analysis was used to examine the association between perceived
      discrimination and well-being. RESULT: As a group, employed workers who were
      exposed to discrimination had a significantly higher likelihood of "poor well
      being" than their counterparts who were not exposed to discrimination. More
      specifically, the workers exposed to age discrimination had an odds ratio(OR) of
      1.51 (95% CI: 1.36-1.68), workers exposed to discrimination based on educational
      attainment had an OR of 1.43 (95% CI: 1.26-1.61), and workers exposed to
      discrimination based on employment type had an OR of 1.68 (95% CI: 1.48-1.91)
      with respect to poor well-being. Furthermore, workers exposed to a greater number
      of discriminatory incidents were also at a higher risk of "poor well-being" than
      their counterparts who were exposed to fewer such incidents. More specifically,
      the workers with three exposures to discrimination had an OR of 2.60 (95% CI:
      1.92-3.53), the workers with two such exposures had an OR of 1.69 (95% CI: 1.44
      1.99), and the workers with one such exposure had an OR of 1.32 (95% CI: 1.20
      1.45). CONCLUSION: The present study found that discrimination based on age,
      educational attainment, or employment type put workers at a higher risk of "poor
      well-being," and that the greater the exposure to discrimination, the higher the
      risk of poor well-being.

PMID- 29026615
TI  - An unusual cutaneous infection caused by Mycobacterium marinum.
AB  - Introduction.Mycobacterium marinum is a non-tubercular mycobacterium residing in
      fresh or salt water (in tropical or temperate areas); it is a fish and human
      pathogen, and in immunocompromised patients can cause severe cutaneous and
      subcutaneous infections. Case presentation. A 46-year-old white man who underwent
      immunosuppressive therapy was admitted to our department in May 2016 for skin
      lesions previously diagnosed as 'unusual erysipelas'. We rejected the hypothesis
      of erysipelas, due to the clinical features, and our diagnostic hypotheses were
      oriented towards sporotrichosis, atypical mycobacteriosis, cutaneous tuberculosis
      and cutaneous sarcoidosis. Histological examination performed after a skin biopsy
      was compatible with a diagnosis of sporotrichosis. However, PCR performed on
      fresh tissue demonstrated the presence of M. marinum. Conclusion. The case
      reported is interesting for the unusual clinical localization and modality of
      infection. The patient became infected by contact with contaminated remains or in
      the sea, in a geographical area not endemic for M. marinum. The previous state of
      immunosuppression favoured infection; however, the presence of M. marinum in this
      area suggests a possible tropicalization of the water of the Mediterranean Sea.
      To our knowledge, this case is the only one reported in the literature with this
      modality of infection and in that geographical area.

PMID- 29026616
TI  - First report of fatal disseminated microsporidiosis in two inland bearded dragons
      Pogona vitticeps in Japan.
AB  - Introduction.Encephalitozoon pogonae is a newly described pathogen belonging to
      the phylum Microsporidia. In Austria and the USA, this species has been isolated
      from fatal and disseminated cases of captive-bred inland bearded dragons. Here,
      we report the case of fatal disseminated microsporidiosis caused by E. pogonae in
      two bearded dragons in Japan. Case Presentation. The two lizards from different
      private households in Tokyo, Japan, had been brought to an animal hospital for
      examination. In both cases, the animal presented with a history of weight loss
      for several weeks. There were no improvements in clinical symptoms and the
      lizards deteriorated and finally died. Histopathological examination demonstrated
      necrotizing granulomatous inflammation attributed to disseminated microsporidian
      infection. Nucleotide sequencing of the nuclear ribosomal internal transcribed
      spacer region identified the microsporidian as E. pogonae with sequence identity
      of 100 %. Conclusion. We report the first case, to our knowledge, of disseminated
      microsporidiosis caused by E. pogonae in inland bearded dragons in Japan.
      Although it is difficult to diagnose prenatally since the signs are nonspecific,
      the disease should be considered in the differential diagnosis of chronic
      infections that do not respond to antibiotics.

PMID- 29026618
TI  - A case of polymicrobial anaerobic spondylodiscitis due to Parvimonas micra and
      Fusobacterium nucleatum.
AB  - Introduction. Here, we present a case of polymicrobial anaerobic
      spondylodiscitis. Case Presentation. A forty-five year-old female patient was
      referred to a specialist orthopaedic hospital with an eight week history of back
      pain without fevers. X-ray imaging and magnetic resonance imaging showed acute
      osteomyelitis of the twelfth thoracic and first lumbar vertebrae. Prolonged
      enrichment cultures grew Parvimonas micra and Fusobacterium nucleatum, identified
      by matrix-assisted laser desorption ionisation-time of flight (MALDI-ToF) mass
      spectrometry (MS). The patient was successfully treated with six weeks of
      intravenous ertapenem and oral clindamycin. Conclusion. Anaerobic discitis is
      rare, and polymicrobial discitis is rarer still. A PubMed literature review
      revealed only seven cases of F. nucleatum discitis and only twelve cases of P.
      micra discitis; this includes only one other reported case of a polymicrobial
      discitis due to infection with both anaerobes. We emphasise the importance of
      prolonging enrichment culture and the use of fast yet accurate identification of
      anaerobes using MALDI-ToF MS in these infections.

PMID- 29026617
TI  - Cerebral vasculitis and intracranial multiple aneurysms in a child with Lyme
      neuroborreliosis.
AB  - : Introduction. Lyme borreliosis is a multisystem tick-borne disease caused by
      Borrelia burgdorferi. Neurological manifestations are reported in up to 15 % of
      adult patients with Lyme disease, while the frequency among children is higher.
      The most common manifestations are painful radiculopathy, facial nerve paresis
      and lymphocytic meningitis. Epileptic seizures and cerebral vasculitis with
      stroke or aneurysms are very rare complications. Case presentation. We describe a
      paediatric patient with sensorineural auditory dysfunction, headache, fatigue and
      epileptic seizures as sequelae of meningoencephalitis/Lyme neuroborreliosis (LNB)
      caused by B. burgdorferi. Brain magnetic resonance imaging revealed widespread
      enhancement of the leptomeninges, cranial nerves and artery walls compatible with
      vasculitis and disturbances in cerebrospinal fluid (CSF) circulation. The patient
      was treated with ceftriaxone for 2 weeks. Two years later, the patient had an
      ischemic stroke. Brain magnetic resonance angiography revealed multiple
      aneurysms, which were not present previously. The largest aneurysm was operated
      rapidly. The patient was treated with another course of intravenous ceftriaxone
      for 4 weeks and pulse therapy with corticosteroids. He recovered well.
      CONCLUSION: . This unique case demonstrates complications of LNB that can result
      in serious morbidity or even mortality. Lumbar puncture and analysis should be
      considered for paediatric patients with epileptic seizures or cerebrovascular
      events living in a Lyme borreliosis endemic area.

PMID- 29026619
TI  - 16S rRNA deep sequencing identifies Actinotignum schaalii as the major component
      of a polymicrobial intra-abdominal infection and implicates a urinary source.
AB  - Introduction. It can be difficult to catalogue the individual organisms
      comprising polymicrobial patient infections, both because conventional clinical
      microbiological culture does not facilitate the isolation and enumeration of all
      members of a complex microbial community, and because fastidious organisms may be
      mixed with organisms that grow rapidly in vitro. Empiric antimicrobial treatment
      is frequently employed based on the anatomical site and the suspected source of
      the infection, especially when an appropriately collected surgical specimen is
      not obtained. Case presentation. We present a case of an intra-abdominal
      infection in a patient with complex anatomy and recurrent urinary tract
      infections. Imaging did not reveal a clear source of infection, no growth was
      obtained from urine cultures and initial abdominal fluid cultures were also
      negative. In contrast, 16S rRNA deep sequencing of abdominal fluid samples
      revealed mixed bacterial populations with abundant anaerobes, including
      Actinotignum schaalii (Actinobaculum schaalii). Ultimately, only Enterobacter
      cloacae complex and meticillin-resistant Staphylococcus aureus, both of which
      were identified by sequencing, were recovered by culture. Conclusion. The
      clinical application of 16S rRNA deep sequencing can more comprehensively and
      accurately define the organisms present in an individual patient's polymicrobial
      infection than conventional microbiological culture, detecting species that are
      not recovered under standard culture conditions or that are otherwise unexpected.
      These results can facilitate effective antimicrobial stewardship and help
      elucidate the possible origins of infections.

PMID- 29026620
TI  - Streptococcus suis serotype 9 endocarditis and subsequent severe meningitis in a
      growing pig despite specific bactericidal humoral immunity.
AB  - INTRODUCTION: . Meningitis and endocarditis are common pathologies of
      Streptococcussuis infections in pigs and humans. S. suis serotype 9 strains
      contribute substantially to health problems in European pig production, and
      immune prophylaxis against this serotype is very difficult. CASE PRESENTATION: .
      We report the clinical course and histopathological picture of a 10-week-old
      growing pig following experimental intravenous infection with S. suis serotype 9.
      The piglet showed rapid onset of severe clinical signs of meningitis 11 days post
      intravenous challenge following prime-booster vaccination. Histopathological
      findings revealed a diffuse fibrinosuppurative leptomeningitis. Additionally, a
      polyphasic endocarditis valvularis thromboticans with numerous bacterial colonies
      was diagnosed. Bacteriological culture of the brain and the mitral valve
      confirmed association with the challenge strain. However, virulent serotype 2 and
      9 strains were killed in the blood of this piglet ex vivo prior experimental
      infection. CONCLUSION: . Endocarditis induced by S. suis infection might develop
      and persist despite the presence of high specific bactericidal activity in the
      blood. Severe leptomeningitis is a putative sequela of such an endocarditis.

PMID- 29026621
TI  - Aeromonas species endogenous endophthalmitis.
AB  - INTRODUCTION: Aeromonas spp. are Gram-negative bacteria classically associated
      with water sources and a variety of clinical infections in humans. CASE
      PRESENTATION: A 79-year-old female patient presented with gastroenteritis with
      associated Aeromonas spp. bloodstream infection. Two days after admission she
      developed eye symptoms and was diagnosed with endophthalmitis and underwent
      emergency evisceration and implant. Aeromonas spp. was also recovered from intra
      ocular samples. CONCLUSION: In this case gastroenteritis caused by Aeromonas spp.
      was complicated by bloodstream infection which seeded to the eye, resulting in
      rapidly progressive endogenous endophthalmitis.

PMID- 29026622
TI  - Lower extremity mycotic aneurysm in a patient with Listeria monocytogenes -
      associated prosthetic valve endocarditis.
AB  - Introduction.Listeria monocytogenes is a rare etiology of infectious endocarditis
      with only 30 cases of prosthetic valve and about twice as many native valve
      infections described in the literature. We describe an unusual presentation of an
      endovascular embolic phenomenon with associated lower extremity mycotic aneurysm
      due to Listeria monocytogenes prosthetic aortic valve and aortic endograft
      infection. Case presentation. This is a case of an elderly gentleman with prior
      history of bioprosthetic aortic valve placement and aortic arch repair who was
      admitted with several weeks of constitutional symptoms and left lower leg pain.
      Diagnostic work-up was consistent with thrombosed popliteal artery aneurysm.
      Blood cultures were positive for Listeria monocytogenes. A transesophageal
      echocardiogram revealed vegetation on the bioprosthetic valve. The patient
      underwent arterial bypass and ligation of the aneurysm as well as redoing of his
      aortic valve and aortic graft replacement. Histopathology of the aortic valve was
      remarkable for acute inflammation and Gram-positive coccobacilli and bacilli
      occupying intracellular spaces. The results of broad-range bacterial 16S rRNA PCR
      and sequence analysis of unfixed aortic valve tissue confirmed detection of L.
      monocytogenes. Conclusion. Infective endocarditis attributable to species of the
      genus Listeriais a rare entity. As such, there are no specific guidelines for
      treatment of Listeria monocytogenesendocarditis. However, combination of
      penicillin or ampicillin with gentamicin is the most acceptable approach
      described in the literature. Our patient was treated with ampicillin and
      gentamicin for 6 weeks followed by life-long amoxicillin suppression therapy. The
      patient remained asymptomatic at a 6 months follow up visit.

PMID- 29026623
TI  - A case of Vibrio vulnificus infection complicated with fulminant purpura: gene
      and biotype analysis of the pathogen.
AB  - Introduction.Vibrio vulnificus (V. vulnificus) causes a severe infection that
      develops in the compromised host. Its pathophysiology is classified into three
      types: (1) primary septicaemia, (2) gastrointestinal illness pattern and (3)
      wound infection pattern. Of these, primary septicaemia is critical. V. vulnificus
      can be classified into three biotypes and two genotypes and its pathogenicity is
      type-dependent. Case presentation. A 47-year-old man presented to a local
      hospital with chief complaints of fever, bilateral lower limb pain and diarrhoea.
      He had no history of foreign travel or known medical problems. He was in septic
      shock and developed fulminant purpura within 24 h of the onset. High-dose
      vasopressor and antibiotic administration failed to alter his status and he died
      3 days after the onset of symptoms. V. vulnificus was isolated from blood, skin
      and nasal discharge cultures. Biotype and gene analysis of the microbe isolated
      identified it as Biotype 3, mainly reported in Israel in wound infections, and
      Genotype E, implicating an environmental isolate. These typing analyses indicated
      that the microbe isolated could be classified as a type with low pathogenicity.
      Conclusion. This case highlighted that Biotype 3 and Genotype E can also cause
      primary septicaemia. Although the majority of reports on Biotype 3 have been from
      the Middle East, this experience with the present case provided evidence that the
      habitat of Biotype 3 V. vulnificus has been extending to East Asia as well.

PMID- 29026624
TI  - First case of human peritoneal cysticercosis mimicking peritoneal carcinosis:
      necessity of laparoscopy and histologic assessment for the correct diagnosis.
AB  - Introduction. Correct diagnosis of peritoneal infectious disease can be extremely
      difficult due to non-specific clinical features. Thus, careful assessment with
      thorough histopathological work-up is essential. Here, we report the first case
      of human peritoneal cysticercosis mimicking peritoneal carcinosis. Case
      presentation. The patient presented with recurring ascites and a tumour in the
      Douglas cavity accompanied by elevated tumour markers. There were no signs of
      systemic infection. On laparoscopy, the tumour was resected completely. Histology
      revealed a granulomatous reaction and a diagnosis suspicious of tuberculosis was
      made. Only after additional sections, avital cestode-fragments were visible and
      Taenia martis DNA was detected. Further staging by computerized tomography scan
      of the lung and brain turned out negative and the patient recovered quickly.
      Conclusion. Laparoscopy and histopathological examination can be extremely
      helpful for correct diagnosis and management in uncertain recurrent ascites. This
      case clearly demonstrates that orphan infectious diseases should also be
      considered. Only complete histopathological examination with serial sections and
      additional molecular testing can lead to the appropriate diagnosis.

PMID- 29026625
TI  - Rash and hepatosplenomegaly in a newborn.

PMID- 29026626
TI  - Acute diarrhoea due to a Shiga toxin 2e-producing Escherichia coli O8 : H19.
AB  - Introduction. Identification of non-O157 Shiga-toxin-producing Escherichia coli
      (STEC) infections may be underestimated in microbiological diagnosis. Case
      presentation. A 58-year-old woman developed diarrhoea with watery and
      subsequently mucous stool. Initial multiplex PCR testing revealed a positive
      result for stx2 . Culture isolation of a STEC was successful only after repeated
      inoculation of chromogenic E. coli media. Molecular characterization was
      performed and identified the isolate as stx2e-positive STEC of serotype O8 : H19.
      The strain harboured lpfA, but not eae. Conclusion. This case highlights the
      usefulness of initial multiplex PCR for diagnosis of non-O157 STEC infection.

PMID- 29026627
TI  - Marked peripheral eosinophilia due to prolonged administration of posaconazole.
AB  - Introduction. Posaconazole is a triazole antifungal that is used in the treatment
      of a variety of fungal infections, as well as in the management of mucormycosis
      (on an off-label basis). Eosinophilia associated with exposure to azole
      antifungals has been described rarely in the literature. Case presentation. A 31
      year-old male on peritoneal dialysis (PD) for end-stage renal disease, secondary
      to diabetic nephropathy, presented to hospital with abdominal pain after a trip
      to St Lucia. He was taken to the operating room, where the PD catheter was
      removed and an abdominal-wall abscess was debrided. Rhizopus species was
      recovered on culture of the abdominal-wall tissue, and the patient was started on
      amphotericin B deoxycholate. He was subsequently stepped down to posaconazole,
      for a planned treatment duration of 12 months. Approximately 43 days after the
      initiation of posaconazole, it was noted that his peripheral eosinophil count
      started to rise. No other cause for the eosinophilia was identified. Posaconazole
      was discontinued, and the patient's eosinophil count began to drop 2 days later.
      The temporal association of eosinophilia following initiation of posaconazole and
      the subsequent improvement after drug discontinuation suggests a probable causal
      relationship. Conclusion. At the time of writing, there have been only two other
      published cases of azole-associated peripheral eosinophilia. In reporting this
      case, we hope to increase health-care provider awareness of this rare adverse
      event. For patients receiving prolonged therapy with posaconazole, periodic
      monitoring of the complete blood count with differential may be considered.

PMID- 29026628
TI  - Cutaneous fungal infection in an immunocompromised host.

PMID- 29026629
TI  - A case of Exophiala dermatitidis infection in a child after allogeneic stem cell
      transplantation: case report and literature review of paediatric cases.
AB  - Introduction.Exophiala dermatitidisis a relatively common environmental black
      yeast with worldwide distribution and is a rare cause of fungal infection, mostly
      in patients with certain predisposing factors. Due to the rarity of the
      infection, little is known about the specific predisposing factors, way of
      infection or treatment. Case presentation. Here, we report what is to our
      knowledge the first case of E. dermatitidis infection in a child after allogeneic
      stem cell transplantation. We also review all paediatric cases reported in the
      literature since 1993. Conclusion. This is, to our knowledge, the first reported
      case of E. dermatitidis infection in a child after allogeneic stem cell
      transplantation. This report should increase the awareness of E. dermatitidis in
      immunocompromised paediatric patients, particularly after stem cell
      transplantation.

PMID- 29026630
TI  - Sinister seafood: bacteraemia secondary to non-O1/O139 Vibrio cholerae infection.
AB  - Introduction.Vibrio species are curved, motile Gram-negative bacilli found in
      estuarine and marine environments, and are known to cause to gastroenteritis,
      skin and soft tissue infections, and septicaemia. While not responsible for
      cholera epidemics, non-O1/O139 Vibrio cholerae (NOVC) is increasingly reported as
      a cause of gastroenteritis. Case presentation. A 66-year-old man presented to an
      emergency department with a 1 week history of epigastric pain, emesis and fever.
      Blood cultures drawn on admission initially demonstrated Gram-negative bacilli,
      and ultimately grew NOVC, which was later confirmed by matrix-assisted laser
      desorption ionization-time of flight MS. Subsequent history revealed that the
      patient had eaten fish and seafood prior to falling ill. He was treated with
      intravenous ceftriaxone and oral doxycycline while admitted, and oral
      ciprofloxacin and doxycycline upon discharge. His bacteraemia was believed to be
      secondary to altered gut anatomy from prior surgery and proton-pump inhibitor
      use. Conclusion. Risk factors for NOVC bacteraemia include cirrhosis,
      immunosuppression and other forms of liver disease. Cases are often linked to a
      history of seafood ingestion when water temperatures rise, enabling Vibrio
      species to proliferate. While the optimal management of NOVC bacteraemia is
      unclear, a combination of a third-generation cephalosporin with a tetracycline
      has been suggested. Physicians should maintain a high index of suspicion for this
      pathogen when evaluating ill patients with a history of liver disease and seafood
      ingestion.

PMID- 29026631
TI  - Salmonella Typhimurium gastroenteritis leading to chronic prosthetic vascular
      graft infection.
AB  - Introduction. It is estimated up to 6 % of prosthetic vascular grafts become
      infected. Staphylococcus aureus is predominant in early infection and coagulase
      negative staphylococci are predominant in late infections. Enterobacteriaceae
      cause 14-40 % of prosthetic vascular graft infections. This is, to our knowledge
      the first reported case of Salmonella gastroenteritis causing chronic prosthetic
      vascular graft infection (PVGI). Case presentation. A 57 years old lady presented
      with signs and symptoms of prosthetic vascular graft infection. Three years
      earlier, she had undergone a prosthetic axillo-femoral bypass graft for critical
      limb ischaemia. The infected prosthetic vascular graft was removed and Salmonella
      Typhimurium was isolated on culture. In the intervening period, Salmonella
      Typhimurium was isolated from a faecal specimen, collected during an episode of
      acute gastroenteritis. Whole-genome sequencing (WGS) showed that the respective
      Salmonella Typhimurium isolates differed by only a single nucleotide polymorphism
      (SNP). Salmonella Typhimurium was not isolated on culture of a faecal specimen
      collected five days following cessation of antimicrobial therapy. Six months
      after removal of the prosthetic graft, the patient remains under follow-up for
      her peripheral vascular disease, which currently requires no further surgical
      intervention. Conclusion. This case has clear implications for the management of
      chronic PVGI. It is vital to collect high-quality surgical specimens for
      microbiological analysis and empirical choices of antibiotics are unlikely to
      cover all potential pathogens. It may also be prudent to enquire about a history
      of acute gastroenteritis when assessing patients presenting with chronic PVGI.

PMID- 29026632
TI  - Salmonella Oranienburg haemorrhagic cystitis in an immunocompetent young male.
AB  - Introduction. Non-typhoidal salmonella (NTS) bacteriuria is extremely rare.
      Haemorrhagic cystitis is defined by urinary symptoms including haematuria,
      frequency, urgency and dysuria. Reports of haemorrhagic cystitis caused by NTS
      are exceptionally uncommon, especially in immunocompetent, young, male patients.
      Case presentation. A 27-year-old male with no past medical history presented to
      the Emergency Department with a 24 h history of visible haematuria having
      returned five days earlier from a five month trip across South America. He also
      reported one week of suprapubic pain with associated dysuria, frequency,
      difficulty voiding and fevers. A non-contrast abdominal and pelvic CT scan showed
      a grossly thick-walled bladder with marked peri-vesical stranding, strongly
      suggestive of cystitis, with an unremarkable appearance of the remainder of the
      urinary tract. Urine culture at presentation subsequently grew Salmonella
      Oranienburg. The patient reported total symptomatic relief following just one
      week of oral antibiotics with no recurrence to date. Conclusion. NTS urinary
      tract infection (UTI), especially in healthy young people, is very rare. In such
      cases, the existence of underlying diseases must be considered, especially
      diabetes mellitus, urological abnormalities and immunosuppression. However, a
      diagnosis of NTS UTI should also be among the differentials in those presenting
      with acute urinary symptoms preceded by gastrointestinal upset, especially
      following travel in underdeveloped countries. Antibiotic therapy is invariably
      indicated and close follow-up is warranted due to the risk of several potentially
      serious complications.

PMID- 29026633
TI  - The first fatal case of Corynebacterium ulcerans infection in Japan.
AB  - Introduction.Corynebacterium ulcerans (C. ulcerans) is a zoonotic pathogen that
      occasionally causes diphtheria-like symptoms in humans. Cases of C. ulcerans
      infection have been increasing in recent years, and C. ulcerans has been
      recognized as an emerging pathogen. Case presentation. Here we report a case of
      asphyxia death due to pseudomembrane caused by diphtheria toxin (DT)-producing C.
      ulcerans. This is, to our knowledge, the first fatal case of C. ulcerans
      infection in Japan. A strain of C. ulcerans was obtained from the patient's pet
      cat and was confirmed to be identical to the patient's isolate by sequencing of
      the 16S rRNA gene and the DT gene, by pulsed-field gel electrophoresis (PFGE) and
      by ribotyping. In the same way, it was revealed that the isolate in this case
      belonged to the same molecular type as the C. ulcerans 0102 isolated from the
      first case in Japan in a distant prefecture 15 years earlier, in 2001.
      Conclusion. DT-producing C. ulcerans can be contracted from a companion animal
      and causes human death if the appropriate treatment is delayed. The finding
      indicates that this molecular type of virulent C. ulcerans is currently
      widespread in Japan.

PMID- 29026634
TI  - HIV positive patient with GBS-like syndrome.
AB  - : Introduction. Guillain-Barre Syndrome (GBS) is an acute demyelinating
      polyneuropathy which can occur post-infection. Criteria of diagnosis of GBS
      include areflexia with progressive bilateral weakness in arms and legs. GBS can
      lead to severe respiratory and cardiac complications. The fatality rate can be up
      to 5 % in patients, depending on the severity of the symptoms. HIV can cause a
      range of neurological disorders including, on rare occasions, GBS. GBS can occur
      at any stage of HIV infection, highlighting the complexity of diagnosis of GBS
      within HIV patients. Case presentation. A 57 year old female with lumbar back
      pain radiating to the legs, poor mobility and tiredness, with reports of a viral
      like illness four days previously, was initially diagnosed with a lower
      respiratory tract infection and discharged. Seventeen days later the patient was
      readmitted to hospital with progressive lower and upper limb weakness, areflexia
      and sensory loss. She was diagnosed with GBS and was unexpectedly discovered to
      be HIV-positive. HIV avidity was low indicating a recently acquired HIV
      infection. The patient was treated with intravenous immunoglobulin for five days
      for the GBS and commenced antriretrovirals for HIV. The patient was discharge
      from hospital 53 days after admission with walking aids and regular physiotherapy
      follow-up. CONCLUSION: . This case highlighted the need for all clinicians to be
      aware that patients with symptoms of GBS, regardless of clinical history should
      be offered an HIV test. GBS can be the first sign a patient is HIV-positive.

PMID- 29026635
TI  - Lytic lesions: looking lethal but leaving room for a simple cure? A case of
      Veillonella spinal osteomyelitis.
AB  - Introduction. Diagnosing clinically significant infection caused by Veillonella
      species can be a challenge. Veillonella species are usually found in
      polymicrobial processes and are often regarded as a contaminant. Additionally,
      they are slow to grow in culture and this can lead to a delay in diagnosis or a
      missed diagnosis. Veillonella species rarely cause serious infections, but have
      been found to cause bacteraemia and osteomyelitis. Case presentation. A 67-year
      old man with a history of treated prostate cancer presented with 2 weeks of
      progressive lower back pain and weakness. He had no signs or symptoms of active
      infection. He was found to have multiple lytic lesions in his lumbar spine that
      were initially suspected to be secondary to metastatic cancer. However, tissue
      and blood cultures were ultimately consistent with infection by Veillonella
      species. Conclusion. This case report highlights the fact that uncommon illnesses
      can often present like common disease processes. Because of the radiological
      appearance of the patient's lesions and his lack of infectious symptoms, a
      diagnosis of metastatic cancer was initially thought to be likely. Relying on the
      pathology and culture data, and waiting on the initiation of antimicrobials until
      the diagnosis was accurately established, were important factors in diagnosing
      and treating this infection. Veillonella species can be true pathogens when found
      in isolation and associated with bacteraemia. Additionally, they can cause an
      indolent infection that can lead to osteomyelitis. Failure to accurately diagnose
      this infection in a timely manner would have led to ongoing debility and
      diagnostic uncertainty for this patient.

PMID- 29026636
TI  - Neck abscess due to Salmonella Choleraesuis: case study and literature review.
AB  - Introduction. We herein describe a case with a neck abscess due to non-typhoidal
      Salmonella (NTS). NTS habitually reside in our environment and colonize all
      animals including mammals. Colonizations of pigs, chickens, cows and sheep are
      important because food poisoning episodes in human are often associated with
      meat. Extra-intestinal infection due to NTS has numerous presentations and
      complications, with aortic aneurysms being common. Case presentation. A 26-year
      old Japanese male complaining of left-sided neck swelling was referred to our
      hospital for a suspected deep neck abscess. An enhanced computed tomography scan
      of the neck revealed a low density lesion in the left-sided deep neck area, and
      consequently the patient underwent urgent incision and drainage. After this
      urgent operation, Salmonella Choleraesuis was isolated from a greyish-white
      abscess. The patient ultimately recovered with antimicrobial administration,
      though re-incision for lymphadenectomy was necessary. The neck abscess may have
      developed because he had eaten raw meat. Furthermore, untreated diabetes mellitus
      was diagnosed at presentation. Conclusion.Salmonella enterica serovar
      Choleraesuis infections are rare in Japan. NTS are generally recognized as
      important pathogens in food poisoning globally, and attention is required to
      avoid the development of extra-intestinal infections. In Japan, the increasing
      lifestyle diversity in recent years highlights the importance of recognizing rare
      infections.

PMID- 29026638
TI  - Effect of antimicrobials administered via liquid feed on the occurrence of
      sulphonamide and trimethoprim resistant Enterobacteriaceae: case-control study.
AB  - BACKGROUND: Drugs for the treatment of groups of pigs receiving liquid feed are
      frequently mixed into the feed and administered via the pipelines of the feeding
      installations. In-feed antimicrobials may select antimicrobial resistant strains
      among the bacteria which form the biofilm of these pipelines and are shed into
      the liquid feed. OBJECTIVE AND METHODS: In order to evaluate the risk of
      selecting antimicrobial resistant bacteria in the biofilm of liquid feeding
      installations, the effect of the administration of antimicrobials via the
      pipelines on the occurrence of antimicrobial resistance in the feed was examined
      in a case-control study. A premix containing either sulphonamide plus
      trimethoprim or sulphonamide plus chlortetracycline plus tylosin or
      chlortetracycline was administered via the pipelines to each batch of bought-in
      fattening pigs in 7, 3 and 3 case farms respectively, whereas antimicrobials had
      not been administered via the liquid feeding installation for at least 2 years in
      the 14 control farms. Enterobacteriaceae and sulphonamide-trimethoprim resistant
      Enterobacteriaceae were counted in twelve and eight feed samples collected in
      each case and in each control farm respectively during one fattening period. The
      semiparametric Generalized Estimating Equations (GEE) method was used for the
      statistical data analysis. RESULTS: The ratio of sulphonamide and trimethoprim
      resistant to total Enterobacteriaceae was higher in the feed of the case farms
      compared to the control farms (P < 0.001) and did not decrease after treatment
      during the fattening period. CONCLUSION: The administration of antimicrobials via
      the liquid feeding installation selects antibiotic resistant bacteria in the
      biofilm lining the pipelines, which may contaminate the liquid feed for extended
      periods and transmit their resistance genes to the gastrointestinal flora of the
      pigs. Alternatives to the administration of antimicrobials via pipelines of
      liquid feeding installations for group treatment should be developed.

PMID- 29026637
TI  - A review of selected Arboviruses during pregnancy.
AB  - Arboviruses are emerging infectious diseases with the ability to expand
      geographically and rapidly affect large populations. The recent epidemic caused
      by the Zika virus in the Americas and congenital Zika syndrome associated with
      maternal infection has called out attention to the importance of studying
      arboviruses during pregnancy. This is a review on selected arboviruses infections
      during gestation, including Zika, Chikungunya, Dengue and Yellow Fever viruses.
      Issues such as historical overview, pathogenesis, transmission, clinical
      conditions, diagnosis, treatment and prevention are addressed.

PMID- 29026639
TI  - Optimising the acceptability and feasibility of novel complex interventions: an
      iterative, person-based approach to developing the UK Morita therapy outpatient
      protocol.
AB  - BACKGROUND: The aim of this paper is to showcase best practice in intervention
      development by illustrating a systematic, iterative, person-based approach to
      optimising intervention acceptability and feasibility, as applied to the cross
      cultural adaptation of Morita therapy for depression and anxiety. METHODS: We
      developed the UK Morita therapy outpatient protocol over four stages integrating
      literature synthesis and qualitative research. Firstly, we conducted in-depth
      interviews combining qualitative and cognitive interviewing techniques, utilising
      vignettes of Morita therapy being delivered and analysed using Framework analysis
      to investigate potential patients and therapists' perceptions of Morita therapy.
      Secondly, we developed qualitative themes into recommendations for optimising
      Morita therapy and synthesised Morita therapy literature in line with these to
      develop a draft protocol. Thirdly, we conducted repeat interviews with therapists
      to investigate their views of the protocol. Finally, we responded to these
      qualitative themes through protocol modification and tailoring our therapist
      training programme. RESULTS: As a consequence of literature describing Morita
      therapy and participants' perceptions of the approach, we developed both a
      therapy protocol and therapist training programme which were fit for purpose in
      proceeding to a UK-based Morita therapy feasibility study. As per our key
      qualitative findings and resulting recommendations, we structured our protocol
      according to the four-phased model of Morita therapy, included detailed guidance
      and warning points, and supported therapists in managing patients' expectations
      of the approach. CONCLUSIONS: Our systematic approach towards optimising
      intervention acceptability and feasibility prioritises the perspectives of those
      who will deliver and receive the intervention. Thus, we both showcase best
      practice in intervention development and demonstrate the application of this
      process to the careful cross-cultural adaptation of an intervention in which
      balancing both optimisation of and adherence to the approach are key. This
      presentation of a generalisable process in a transparent and replicable manner
      will be of interest to those both developing and evaluating complex interventions
      in the future.

PMID- 29026640
TI  - Directing the osteoblastic and chondrocytic differentiations of mesenchymal stem
      cells: matrix vs. induction media.
AB  - While both induction culture media and matrix have been reported to regulate the
      stem cell fate, little is known about which factor plays a more decisive role in
      directing the MSC differentiation lineage as well as the underlying mechanisms.
      To this aim, we seeded MSCs on HA-collagen and HA-synthetic hydrogel matrixes,
      which had demonstrated highly different potentials toward osteoblastic and
      chondrocytic differentiation lineages, respectively, and cultured them with
      osteogenic, chondrogenic and normal culture media, respectively. A systematic
      comparison has been carried out on the effects of induction media and matrix on
      MSC adhesion, cytoskeleton organization, proliferation, and in particular
      differentiation into the osteoblastic and chondrocytic lineages. The results
      demonstrated that the matrix selection had a much more profound effect on
      directing the differentiation lineage than the induction media did. The strong
      modulation effect on the transcription activities might be the critical factor
      contributing to the above observations in our study, where canonical Wnt-beta
      Catenin signal pathway was directly involved in the matrix-driven osteoblastic
      differentiation. Such findings not only provide a critical insight on natural
      cellular events leading to the osteoblastic and chondrocytic differentiations,
      but also have important implications in biomaterial design for tissue engineering
      applications.

PMID- 29026641
TI  - Surface hydrolysis-mediated PEGylation of poly(N-isopropyl acrylamide) based
      nanogels.
AB  - In this work, poly(N-isopropyl acrylamide-co-acrylamide) [P(NIPAAm-co-AAm)]
      nanogels were modified by hydrolysis above the lower critical solution
      temperature (LCST) to localize carboxylic acid functional groups at the surface
      (surface hydrolysis). PNIPAAm copolymerized with 15% and 20% nominal AAm in the
      feed were prepared and compared to equivalent hydrogels with acrylic acid. The
      effect and extent of surface hydrolysis was confirmed by potentiometric titration
      and zeta potential. These surface modified nanogels were then modified with
      primary amine functionalized PEG chains. Surface hydrolysis-mediated PEGylation
      had little effect on the swelling response of the nanogels, while also preventing
      adsorption of model proteins in physiological relevant conditions. While both 15%
      and 20% AAm gels both decreased protein adsorption, only the 20% AAm gels
      resulted in fully preventing protein adsorption. The results presented here point
      to surface hydrolysis as a new route to passivate nanogels for use in vivo.

PMID- 29026643
TI  - Mineralized collagen artificial bone repair material products used for fusing the
      podarthral joints with internal fixation-a case report.
AB  - In this study, we reported a case with collapse and subluxation of metatarsal
      cuneiform joint, navicular-cuneiform joint with subluxed the right first
      metatarsophalangeal joint. The injured medial column was internally fixed with
      compression arthrodesis. The fusion site was firmed up with BonGold(r) Bone
      Sponge and Bone Putty. The prognosis of fused navicular-cuneiform joint and
      metatarsal-cuneiform joint were examined by X-ray shortly after surgical
      operation and followed up 2, 4, 6, 9 and 13 weeks after the surgical operation.
      The medial column was perfectly fused by compression arthrodesis. These results
      justified and favored the application of mineralized collagen as an excellent
      alternative to autograft in fusing the podarthral joints with internal fixation.

PMID- 29026642
TI  - Locking system strengthened by biomimetic mineralized collagen putty for the
      treatment of osteoporotic proximal humeral fractures.
AB  - The current study is to observe the effect of the locking system strengthened by
      biomimetic mineralized collagen putty for the treatment of senile proximal
      humeral osteoporotic fractures. From January 2012 to December 2015, 80 cases of
      senile patients with osteoporotic proximal humeral fractures were randomly
      divided into an observation group and a control group, each group with a total of
      40 cases. The control group was simply treated with locking plate. The
      observation group was treated with locking plate in combination with biomimetic
      mineralized collagen putty. The therapeutic effect thereby was observed. The
      excellent and satisfactory rate was 90% in observation group and was 72.5% in
      control group. The difference between the two groups was statistically
      significant (chi2 = 5.3312, P < 0.05). The fracture healing time was 11.82 +/-
      3.62 weeks in observation group and 19.78 +/- 5.46 weeks in control group. The
      shoulder joint function score was 89.63 +/- 8.12 in observation group and 76.92
      +/- 8.18 in control group. There was significant difference between the two
      groups (t = 7.1272; 12.7834, P < 0.05). The complication rate was 10% in the
      observation group and 32.5% in the control group (chi2 = 7.3786, P < 0.05).
      Locking system strengthened by biomimetic mineralized collagen putty has
      advantages such as accelerating healing of senile proximal humeral fracture,
      improving the therapeutic effect, reducing the complications. As one of the
      optimal internal fixation method, it provides a new option for better treatment
      of senile osteoporotic fracture.

PMID- 29026644
TI  - Wet-spinning fabrication of shear-patterned alginate hydrogel microfibers and the
      guidance of cell alignment.
AB  - Native tissue is naturally comprised of highly-ordered cell-matrix assemblies in
      a multi-hierarchical way, and the nano/submicron alignment of fibrous matrix is
      found to be significant in supporting cellular functionalization. In this study,
      a self-designed wet-spinning device appended with a rotary receiving pool was
      used to continuously produce shear-patterned hydrogel microfibers with aligned
      submicron topography. The process that the flow-induced shear force reshapes the
      surface of hydrogel fiber into aligned submicron topography was systematically
      analysed. Afterwards, the effect of fiber topography on cellular longitudinal
      spread and elongation was investigated by culturing rat neuron-like PC12 cells
      and human osteosarcoma MG63 cells with the spun hydrogel microfibers,
      respectively. The results suggested that the stronger shear flow force would lead
      to more distinct aligned submicron topography on fiber surface, which could
      induce cell orientation along with fiber axis and therefore form the cell-matrix
      dual-alignment. Finally, a multi-hierarchical tissue-like structure constructed
      by dual-oriented cell-matrix assemblies was fabricated based on this wet-spinning
      method. This work is believed to be a potentially novel biofabrication scheme for
      bottom-up constructing of engineered linear tissue, such as nerve bundle,
      cortical bone, muscle and hepatic cord.

PMID- 29026645
TI  - Synthesis and characterization of collagen/PLGA biodegradable skin scaffold
      fibers.
AB  - The aim of this study is to investigate the applicability of poly(lactic-co
      glycolic acid) (PLGA)/collagen composite scaffold for skin tissue engineering.
      PLGA and collagen were dissolved in HFIP as a common solvent and fibrous
      scaffolds were prepared by electrospinning method. The scaffolds were
      characterized by scanning electron microscopy (SEM), FTIR spectroscopy, mercury
      porosimetry, tensile strength, biocompatibility assays and Biodegradation.
      Cytotoxicity and cell adhesion were tested for two cell line groups, human dermal
      fibroblast (HDF) and human keratinocyte (HaCat). SEM images showed appropriate
      cell adhesion to the scaffold for both cell lines. MTT assays indicated that the
      cell viability of HDF cells increased with time, but the number of HaCat cells
      decreased after 14 days. The ultimate tensile strength was suitable for skin
      substitute application, but its elongation at break was rather low. For
      successful clinical application of the PLGA/collagen scaffold, some properties
      especially mechanical strain needs to be improved.

PMID- 29026646
TI  - Binary titanium alloys as dental implant materials-a review.
AB  - Titanium (Ti) has been used for long in dentistry and medicine for implant
      purpose. During the years, not only the commercially pure Ti but also some alloys
      such as binary and tertiary Ti alloys were used. The aim of this review is to
      describe and compare the current literature on binary Ti alloys, including Ti-Zr,
      Ti-In, Ti-Ag, Ti-Cu, Ti-Au, Ti-Pd, Ti-Nb, Ti-Mn, Ti-Mo, Ti-Cr, Ti-Co, Ti-Sn, Ti
      Ge and Ti-Ga, in particular to mechanical, chemical and biological parameters
      related to implant application. Literature was searched using the PubMed and Web
      of Science databases, as well as google without limiting the year, but with
      principle key terms such as ' Ti alloy', 'binary Ti ', 'Ti-X' (with X is the
      alloy element), 'dental implant' and 'medical implant'. Only laboratory studies
      that intentionally for implant or biomedical applications were included.
      According to available literatures, we might conclude that most of the binary Ti
      alloys with alloying <20% elements of Zr, In, Ag, Cu, Au, Pd, Nb, Mn, Cr, Mo, Sn
      and Co have high potential as implant materials, due to good mechanical
      performance without compromising the biocompatibility and biological behaviour
      compare to cp-Ti.

PMID- 29026647
TI  - Progress in development of bioderived materials for dermal wound healing.
AB  - Treatment of acute and chronic wounds is one of the primary challenges faced by
      doctors. Bioderived materials have significant potential clinical value in tissue
      injury treatment and defect reconstruction. Various strategies, including drug
      loading, addition of metallic element(s), cross-linking and combining two or more
      distinct types of materials with complementary features, have been used to
      synthesize more suitable materials for wound healing. In this review, we describe
      the recent developments made in the processing of bioderived materials employed
      for cutaneous wound healing, including newly developed materials such as keratin
      and soy protein. The focus was on the key properties of the bioderived materials
      that have shown great promise in improving wound healing, restoration and
      reconstruction. With their good biocompatibility, nontoxic catabolites,
      microinflammation characteristics, as well as their ability to induce tissue
      regeneration and reparation, the bioderived materials have great potential for
      skin tissue repair.

PMID- 29026648
TI  - Clinical impact of skin autofluorescence on high-sensitivity troponin T in
      hypertensive patients.
AB  - BACKGROUND: Recent studies have reported the importance of high-sensitivity
      troponin T (hs-cTnT) or skin autofluorescence (AF) as a cardiovascular risk
      factor. However, little is known about the relationship between these two
      markers. The aim of this study was to clarify the clinical impact of skin AF on
      hs-cTnT in hypertensive patients, from the perspective of primary prevention of
      cardiovascular events. METHODS: In total, 457 outpatients on treatment for
      hypertension [182 men and 275 women; mean (+/- SD) age, 67 +/- 13 y] and with no
      history of cardiovascular events were enrolled. Hs-cTnT levels and skin AF were
      measured using commercial devices, and relationships between hs-cTnT levels and
      various clinical parameters including skin AF were examined. RESULTS: Hs-cTnT was
      detected in 405 (88.6%) patients. Skin AF was significantly higher in patients
      with detectable hs-cTnT than in those without detectable hs-cTnT [2.6 +/- 0.5
      arbitrary units (AU) vs. 2.2 +/- 0.5 AU, respectively, p < 0.001]. In patients
      with detectable hs-cTnT, there was a significantly positive correlation between
      skin AF and Log-hs-cTnT (r = 0.41, p < 0.001). Furthermore, multiple regression
      analysis revealed that skin AF was the strongest variable associated with Log-hs
      cTnT as a subordinate factor (beta = 0.30, p < 0.001). CONCLUSIONS: The results
      of this study indicate that skin AF is an important determining factor for hs
      cTnT elevation in hypertensive patients with no history of cardiovascular events.

PMID- 29026649
TI  - Unique genome organization of non-mammalian papillomaviruses provides insights
      into the evolution of viral early proteins.
AB  - The family Papillomaviridae contains more than 320 papillomavirus types, with
      most having been identified as infecting skin and mucosal epithelium in mammalian
      hosts. To date, only nine non-mammalian papillomaviruses have been described from
      birds (n = 5), a fish (n = 1), a snake (n = 1), and turtles (n = 2). The
      identification of papillomaviruses in sauropsids and a sparid fish suggests that
      early ancestors of papillomaviruses were already infecting the earliest
      Euteleostomi. The Euteleostomi clade includes more than 90 per cent of the living
      vertebrate species, and progeny virus could have been passed on to all members of
      this clade, inhabiting virtually every habitat on the planet. As part of this
      study, we isolated a novel papillomavirus from a 16-year-old female Adelie
      penguin (Pygoscelis adeliae) from Cape Crozier, Ross Island (Antarctica). The new
      papillomavirus shares ~64 per cent genome-wide identity to a previously described
      Adelie penguin papillomavirus. Phylogenetic analyses show that the non-mammalian
      viruses (expect the python, Morelia spilota, associated papillomavirus) cluster
      near the base of the papillomavirus evolutionary tree. A papillomavirus isolated
      from an avian host (Northern fulmar; Fulmarus glacialis), like the two turtle
      papillomaviruses, lacks a putative E9 protein that is found in all other avian
      papillomaviruses. Furthermore, the Northern fulmar papillomavirus has an E7 more
      similar to the mammalian viruses than the other avian papillomaviruses. Typical
      E6 proteins of mammalian papillomaviruses have two Zinc finger motifs, whereas
      the sauropsid papillomaviruses only have one such motif. Furthermore, this motif
      is absent in the fish papillomavirus. Thus, it is highly likely that the most
      recent common ancestor of the mammalian and sauropsid papillomaviruses had a
      single motif E6. It appears that a motif duplication resulted in mammalian
      papillomaviruses having a double Zinc finger motif in E6. We estimated the
      divergence time between Northern fulmar-associated papillomavirus and the other
      Sauropsid papillomaviruses be to around 250 million years ago, during the
      Paleozoic-Mesozoic transition and our analysis dates the root of the
      papillomavirus tree between 400 and 600 million years ago. Our analysis shows
      evidence for niche adaptation and that these non-mammalian viruses have highly
      divergent E6 and E7 proteins, providing insights into the evolution of the early
      viral (onco-)proteins.

PMID- 29026650
TI  - Accurate quantification of within- and between-host HBV evolutionary rates
      requires explicit transmission chain modelling.
AB  - Analyses of virus evolution in known transmission chains have the potential to
      elucidate the impact of transmission dynamics on the viral evolutionary rate and
      its difference within and between hosts. Lin et al. (2015, Journal of Virology,
      89/7: 3512-22) recently investigated the evolutionary history of hepatitis B
      virus in a transmission chain and postulated that the 'colonization-adaptation
      transmission' model can explain the differential impact of transmission on
      synonymous and non-synonymous substitution rates. Here, we revisit this dataset
      using a full probabilistic Bayesian phylogenetic framework that adequately
      accounts for the non-independence of sequence data when estimating evolutionary
      parameters. Examination of the transmission chain data under a flexible
      coalescent prior reveals a general inconsistency between the estimated timings
      and clustering patterns and the known transmission history, highlighting the need
      to incorporate host transmission information in the analysis. Using an explicit
      genealogical transmission chain model, we find strong support for a transmission
      associated decrease of the overall evolutionary rate. However, in contrast to the
      initially reported larger transmission effect on non-synonymous substitution
      rate, we find a similar decrease in both non-synonymous and synonymous
      substitution rates that cannot be adequately explained by the colonization
      adaptation-transmission model. An alternative explanation may involve a
      transmission/establishment advantage of hepatitis B virus variants that have
      accumulated fewer within-host substitutions, perhaps by spending more time in the
      covalently closed circular DNA state between each round of viral replication.
      More generally, this study illustrates that ignoring phylogenetic relationships
      can lead to misleading evolutionary estimates.

PMID- 29026653
TI  - Corrigendum: In silico serotyping of E. coli from short read data identifies
      limited novel O-loci but extensive diversity of O:H serotype combinations within
      and between pathogenic lineages.
AB  - [This corrects the article DOI: 10.1099/mgen.0.000064.].

PMID- 29026652
TI  - Pre-vaccine serotype composition within a lineage signposts its serotype
      replacement - a carriage study over 7 years following pneumococcal conjugate
      vaccine use in the UK.
AB  - Serotype replacement has been reported in carriage and disease after pneumococcal
      conjugate vaccine (PCV) introductions in the UK and globally. We previously
      described concurrent expansion and decline of sequence types associated with
      serotype replacement over 5 years following PCV introductions in the UK. Here we
      use whole-genome sequencing to fully characterise the population structure of
      pneumococcal isolates collected over seven winters encompassing PCV7 and PCV13
      introductions in the UK, investigating the importance of lineages in serotype
      replacement. We analysed 672 pneumococcal genomes from colonised children of 4
      years old or less. The temporal prevalence of 20 lineages, defined by
      hierarchical Bayesian analysis of population structure (BAPS), was assessed in
      the context of serotype replacement. Multiple serotypes were detected in the
      primary winter of sampling within three vaccine-type (VT) lineages BAPS4, BAPS10
      and BAPS11, in which serotype replacement were observed. In contrast, serotype
      replacement was not seen in the remaining three VT lineages (BAPS1, BAPS13 and
      BAPS14), that expressed a single serotype (6B, 6A and 3, respectively) in the
      primary winter. One lineage, BAPS1 serotype 6B was undetectable in the population
      towards the end of the study period. The dynamics of serotype replacement, in
      this UK population, was preceded by the presence or absence of multiple serotypes
      within VT lineages, in the pre-PCV population. This observation could help
      predict which non-vaccine types (NVTs) may be involved in replacement in future
      PCV introductions here and elsewhere. It could further indicate whether any
      antibiotic resistance associated with the lineages is likely to be affected by
      replacement.

PMID- 29026651
TI  - SNVPhyl: a single nucleotide variant phylogenomics pipeline for microbial genomic
      epidemiology.
AB  - The recent widespread application of whole-genome sequencing (WGS) for microbial
      disease investigations has spurred the development of new bioinformatics tools,
      including a notable proliferation of phylogenomics pipelines designed for
      infectious disease surveillance and outbreak investigation. Transitioning the use
      of WGS data out of the research laboratory and into the front lines of
      surveillance and outbreak response requires user-friendly, reproducible and
      scalable pipelines that have been well validated. Single Nucleotide Variant
      Phylogenomics (SNVPhyl) is a bioinformatics pipeline for identifying high-quality
      single-nucleotide variants (SNVs) and constructing a whole-genome phylogeny from
      a collection of WGS reads and a reference genome. Individual pipeline components
      are integrated into the Galaxy bioinformatics framework, enabling data analysis
      in a user-friendly, reproducible and scalable environment. We show that SNVPhyl
      can detect SNVs with high sensitivity and specificity, and identify and remove
      regions of high SNV density (indicative of recombination). SNVPhyl is able to
      correctly distinguish outbreak from non-outbreak isolates across a range of
      variant-calling settings, sequencing-coverage thresholds or in the presence of
      contamination. SNVPhyl is available as a Galaxy workflow, Docker and virtual
      machine images, and a Unix-based command-line application. SNVPhyl is released
      under the Apache 2.0 license and available at http://snvphyl.readthedocs.io/ or
      at https://github.com/phac-nml/snvphyl-galaxy.

PMID- 29026654
TI  - Population genetic structuring of methicillin-resistant Staphylococcus aureus
      clone EMRSA-15 within UK reflects patient referral patterns.
AB  - Antibiotic resistance forms a serious threat to the health of hospitalised
      patients, rendering otherwise treatable bacterial infections potentially life
      threatening. A thorough understanding of the mechanisms by which resistance
      spreads between patients in different hospitals is required in order to design
      effective control strategies. We measured the differences between bacterial
      populations of 52 hospitals in the United Kingdom and Ireland, using whole-genome
      sequences from 1085 MRSA clonal complex 22 isolates collected between 1998 and
      2012. The genetic differences between bacterial populations were compared with
      the number of patients transferred between hospitals and their regional
      structure. The MRSA populations within single hospitals, regions and countries
      were genetically distinct from the rest of the bacterial population at each of
      these levels. Hospitals from the same patient referral regions showed more
      similar MRSA populations, as did hospitals sharing many patients. Furthermore,
      the bacterial populations from different time-periods within the same hospital
      were generally more similar to each other than contemporaneous bacterial
      populations from different hospitals. We conclude that, while a large part of the
      dispersal and expansion of MRSA takes place among patients seeking care in single
      hospitals, inter-hospital spread of resistant bacteria is by no means a rare
      occurrence. Hospitals are exposed to constant introductions of MRSA on a number
      of levels: (1) most MRSA is received from hospitals that directly transfer large
      numbers of patients, while (2) fewer introductions happen between regions or (3)
      across national borders, reflecting lower numbers of transferred patients. A
      joint coordinated control effort between hospitals, is therefore paramount for
      the national control of MRSA, antibiotic-resistant bacteria and other hospital
      associated pathogens.

PMID- 29026655
TI  - Sharing of carbapenemase-encoding plasmids between Enterobacteriaceae in UK
      sewage uncovered by MinION sequencing.
AB  - Dissemination of carbapenem resistance among pathogenic Gram-negative bacteria is
      a looming medical emergency. Efficient spread of resistance within and between
      bacterial species is facilitated by mobile genetic elements. We hypothesized that
      wastewater contributes to the dissemination of carbapenemase-producing
      Enterobacteriaceae (CPE), and studied this through a cross-sectional
      observational study of wastewater in the East of England. We isolated clinically
      relevant species of CPE in untreated and treated wastewater, confirming that
      waste treatment does not prevent release of CPE into the environment. We observed
      that CPE-positive plants were restricted to those in direct receipt of hospital
      waste, suggesting that hospital effluent may play a role in disseminating
      carbapenem resistance. We postulated that plasmids carrying carbapenemase genes
      were exchanged between bacterial hosts in sewage, and used short-read (Illumina)
      and long-read (MinION) technologies to characterize plasmids encoding resistance
      to antimicrobials and heavy metals. We demonstrated that different CPE species
      (Enterobacter kobei and Raoultella ornithinolytica) isolated from wastewater from
      the same treatment plant shared two plasmids of 63 and 280 kb. The former plasmid
      conferred resistance to carbapenems (blaOXA-48), and the latter to numerous drug
      classes and heavy metals. We also report the complete genome sequence for
      Enterobacter kobei. Small, portable sequencing instruments such as the MinION
      have the potential to improve the quality of information gathered on
      antimicrobial resistance in the environment.

PMID- 29026656
TI  - Phylogenomics and comparative genomics of Lactobacillus salivarius, a mammalian
      gut commensal.
AB  - The genus Lactobacillus is a diverse group with a combined species count of over
      200. They are the largest group within the lactic acid bacteria and one of the
      most important bacterial groups involved in food microbiology and human nutrition
      because of their fermentative and probiotic properties. Lactobacillus salivarius,
      a species commonly isolated from the gastrointestinal tract of humans and
      animals, has been described as having potential probiotic properties and results
      of previous studies have revealed considerable functional diversity existing on
      both the chromosomes and plasmids. Our study consists of comparative genomic
      analyses of the functional and phylogenomic diversity of 42 genomes of strains of
      L. salivarius using bioinformatic techniques. The main aim of the study was to
      describe intra-species diversity and to determine how this diversity is spread
      across the replicons. We found that multiple phylogenomic and non-phylogenomic
      methods used for reconstructing trees all converge on similar tree topologies,
      showing that different metrics largely agree on the evolutionary history of the
      species. The greatest genomic variation lies on the small plasmids, followed by
      the repA-type circular megaplasmid, with the chromosome varying least of all.
      Additionally, the presence of extra linear and circular megaplasmids is noted in
      several strains, while small plasmids are not always present. Glycosyl
      hydrolases, bacteriocins and proteases vary considerably on all replicons while
      two exopolysaccharide clusters and several clustered regularly interspaced short
      palindromic repeats-associated systems show a lot of variation on the chromosome.
      Overall, despite its reputation as a mammalian gastrointestinal tract specialist,
      the intra-specific variation of L. salivarius reveals potential strain-dependant
      effects on human health.

PMID- 29026657
TI  - Whole-genome sequencing to investigate a non-clonal melioidosis cluster on a
      remote Australian island.
AB  - Melioidosis is a tropical disease caused by the bacterium Burkholderia
      pseudomallei. Outbreaks are uncommon and can generally be attributed to a single
      point source and strain. We used whole-genome sequencing to analyse B.
      pseudomallei isolates collected from an historical 2-year long case cluster that
      occurred in a remote northern Australian indigenous island community, where
      infections were previously linked to a contaminated communal water supply. We
      analysed the genome-wide relatedness of the two most common multilocus sequence
      types (STs) involved in the outbreak, STs 125 and 126. This analysis showed that
      although these STs were closely related on a whole-genome level, they
      demonstrated evidence of multiple recombination events that were unlikely to have
      occurred over the timeframe of the outbreak. Based on epidemiological and genetic
      data, we also identified two additional patients not previously associated with
      this outbreak. Our results confirm the previous hypothesis that a single
      unchlorinated water source harbouring multiple B. pseudomallei strains was linked
      to the outbreak, and that increased melioidosis risk in this community was
      associated with Piper methysticum root (kava) consumption.

PMID- 29026658
TI  - Resolving plasmid structures in Enterobacteriaceae using the MinION nanopore
      sequencer: assessment of MinION and MinION/Illumina hybrid data assembly
      approaches.
AB  - This study aimed to assess the feasibility of using the Oxford Nanopore
      Technologies (ONT) MinION long-read sequencer in reconstructing fully closed
      plasmid sequences from eight Enterobacteriaceae isolates of six different species
      with plasmid populations of varying complexity. Species represented were
      Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter
      cloacae, Serratia marcescens and Klebsiella oxytoca, with plasmid populations
      ranging from 1-11 plasmids with sizes of 2-330 kb. Isolates were sequenced using
      Illumina (short-read) and ONT's MinION (long-read) platforms, and compared with
      fully resolved PacBio (long-read) sequence assemblies for the same isolates. We
      compared the performance of different assembly approaches including SPAdes,
      plasmidSPAdes, hybridSPAdes, Canu, Canu+Pilon (canuPilon) and npScarf in
      recovering the plasmid structures of these isolates by comparing with the gold
      standard PacBio reference sequences. Overall, canuPilon provided consistently
      good quality assemblies both in terms of assembly statistics (N50, number of
      contigs) and assembly accuracy [presence of single nucleotide polymorphisms
      (SNPs)/indels with respect to the reference sequence]. For plasmid
      reconstruction, Canu recovered 70 % of the plasmids in complete contigs, and
      combining three assembly approaches (Canu or canuPilon, hybridSPAdes and
      plasmidSPAdes) resulted in a total 78 % recovery rate for all the plasmids. The
      analysis demonstrated the potential of using MinION sequencing technology to
      resolve important plasmid structures in Enterobacteriaceae species independent of
      and in conjunction with Illumina sequencing data. A consensus assembly derived
      from several assembly approaches could present significant benefit in accurately
      resolving the greatest number of plasmid structures.

PMID- 29026659
TI  - Emergence and genomic diversification of a virulent serogroup W:ST-2881(CC175)
      Neisseria meningitidis clone in the African meningitis belt.
AB  - Countries of the African 'meningitis belt' are susceptible to meningococcal
      meningitis outbreaks. While in the past major epidemics have been primarily
      caused by serogroup A meningococci, W strains are currently responsible for most
      of the cases. After an epidemic in Mecca in 2000, W:ST-11 strains have caused
      many outbreaks worldwide. An unrelated W:ST-2881 clone was described for the
      first time in 2002, with the first meningitis cases caused by these bacteria
      reported in 2003. Here we describe results of a comparative whole-genome analysis
      of 74 W:ST-2881 strains isolated within the framework of two longitudinal
      colonization and disease studies conducted in Ghana and Burkina Faso. Genomic
      data indicate that the W:ST-2881 clone has emerged from Y:ST-175(CC175) bacteria
      by capsule switching. The circulating W:ST-2881 populations were composed of a
      variety of closely related but distinct genomic variants with no systematic
      differences between colonization and disease isolates. Two distinct and
      geographically clustered phylogenetic clonal variants were identified in Burkina
      Faso and a third in Ghana. On the basis of the presence or absence of 17
      recombination fragments, the Ghanaian variant could be differentiated into five
      clusters. All 25 Ghanaian disease isolates clustered together with 23 out of 40
      Ghanaian isolates associated with carriage within one cluster, indicating that
      W:ST-2881 clusters differ in virulence. More than half of the genes affected by
      horizontal gene transfer encoded proteins of the 'cell envelope' and the
      'transport/binding protein' categories, which indicates that exchange of non
      capsular antigens plays an important role in immune evasion.

PMID- 29026660
TI  - Comparison of classical multi-locus sequence typing software for next-generation
      sequencing data.
AB  - Multi-locus sequence typing (MLST) is a widely used method for categorizing
      bacteria. Increasingly, MLST is being performed using next-generation sequencing
      (NGS) data by reference laboratories and for clinical diagnostics. Many software
      applications have been developed to calculate sequence types from NGS data;
      however, there has been no comprehensive review to date on these methods. We have
      compared eight of these applications against real and simulated data, and present
      results on: (1) the accuracy of each method against traditional typing methods,
      (2) the performance on real outbreak datasets, (3) the impact of contamination
      and varying depth of coverage, and (4) the computational resource requirements.

PMID- 29026662
TI  - Intrathecal and intraventricular antibiotics for postoperative Gram-negative
      meningitis and ventriculitis.
AB  - BACKGROUND: Postoperative meningitis is a growing cause of concern, especially
      with the evolution of multidrug-resistant organism. The authors evaluate the use
      of intraventricular/intrathecal (IVT/IT) antibiotics for postoperative gram
      negative meningitis in patients whom intravenous antibiotics were ineffective.
      METHODS: Medical records were retrospectively reviewed and neurosurgery patients
      with gram-negative postoperative infection meningitis/ventriculitis were enrolled
      in the study. Their demographics, hospital course, and outcomes were recorded in
      a pro forma and analyzed using Statistical Package for the Social Sciences,
      version 19. RESULTS: The review identified 21 patients with postneurosurgical
      gram-negative meningitis/ventriculitis who were treated with IVT or IT
      antibiotics. The most common organism was Acinetobacter species (n = 14; 66%).
      Amikacin was used in 7 patients, polymyxin B in 9 patients, and colistin in 5
      patients. A combination of antibiotics was used in one patient. Cerebrospinal
      fluid sterility was achieved in all patients with no incidence of relapse. There
      was a single death, though that was not related to the infectious process as the
      patient had a massive pulmonary embolism. CONCLUSION: The findings of this study
      suggest that IVT and IT antibiotic therapy is a useful option in patients who are
      nonresponsive to standard intravenous therapy with little or no side effects.

PMID- 29026663
TI  - Ependymal enhancement on magnetic resonance imaging for the identification of
      high-grade gliomas.
AB  - BACKGROUND: High-grade gliomas have high infiltrative potential and spread along
      white matter and blood vessels. Enhancement of ependymal lining on magnetic
      resonance imaging (MRI) is considered as a marker of parenchymal spread of
      disease. In this study, we aimed to assess the sensitivity, specificity, and
      positive and negative predictive values of ependymal enhancement (EE) for
      identification of high-grade glial tumors. METHODS: We reviewed preoperative MRI
      scans of 94 consecutive patients surgically treated for space occupying lesions
      of the brain for EE. Assessment for EE was blind to the final histopathological
      diagnosis of the patient. An enhancement of more than 2 mm was considered
      positive. Pathologies of these patients were reviewed and matched to the
      radiological findings. Percentage and proportion of EE in glial and non-glial
      pathology groups was then calculated and a sensitivity and specificity analysis
      was performed. RESULTS: The population included 94 cases (64 males and 30
      females) with population mean age 45 +/- 15.5 years. Sensitivity of EE in
      differentiating glioma from total number of cases was 82.61% specificity 35.42%
      (P value = 0.048). EE had a sensitivity of 67.39% and specificity of 64.58% (P
      value = 0.002) in identifying high-grade glioma within the glioma group with a
      positive predictive value of 64.58% (95% CI: 49.46% to 77.83%), negative
      predictive value of 67.39% (95% CI: 51.98% to 80.46%). CONCLUSION: EE has
      moderate sensitivity and specificity for high-grade gliomas. However, larger
      sample studies are required for further validation of this observations.

PMID- 29026664
TI  - Supratentorial extraparenchymal schwannoma mimicking parasagittal meningioma: A
      rare case report.
AB  - BACKGROUND: Intracranial schwannomas not related to cranial nerves are very rare.
      Young age, no known history of neurofibromatosis, and seizure as initial symptom
      have been reported to be associated with intraparenchymal schwannoma. CASE
      DESCRIPTION: We report a case of supratentorial parasagittal schwannoma in the
      right frontal region presenting with seizure episode in a 70-year-old man.
      Computed tomography and magnetic resonance imaging showed a right frontal solid,
      enhancing extra-axial lesion based on anterior and middle third junction of
      superior sagittal sinus. The preoperative diagnosis was right parasagittal
      meningioma, however, the microscopic examination of the mass showed the
      characteristic pattern of cellular Antony A pattern. Immunohistocemically, the
      tumor stained positive for S-100 protein but negatively for epithelial membrane
      antigen and glial fibrillary acidic protein. These findings are consistent with
      schwannoma. Cysts, calcification, and peritumoral edema are common in
      intracerebral schwannoma, which were not seen in our case. CONCLUSION: On the
      basis of clinical presentation and radiological appearances, schwannoma in
      unusual sites can easily be mistaken for meningiomas; immunochemistry plays an
      important role in differentiating them. Till date, to the best of our knowledge,
      this is the second reported case of schwannoma mimicking meningioma in
      parasagittal location.

PMID- 29026661
TI  - Tenth case of bilateral hemifacial spasm treated by microvascular decompression:
      Review of the pathophysiology.
AB  - BACKGROUND: Bilateral hemifacial spasm (BHFS) is a rare neurological syndrome
      whose diagnosis depends on excluding other facial dyskinesias. We present a case
      of BHFS along with a literature review. METHODS: A 64-year-old white, hypertense
      male reported involuntary left hemiface contractions in 2001 (aged 50). In 2007,
      right hemifacial symptoms appeared, without spasm remission during sleep.
      Botulinum toxin type A application produced partial temporary improvement. Left
      microvascular decompression (MVD) was performed in August 2013, followed by right
      MVD in May 2014, with excellent results. Follow-up in March 2016 showed complete
      cessation of spasms without medication. RESULTS: The literature confirms nine
      BHFS cases bilaterally treated by MVD, a definitive surgical option with minimal
      complications. Regarding HFS pathophysiology, ectopic firing and ephaptic
      transmissions originate in the root exit zone (REZ) of the facial nerve, due to
      neurovascular compression (NVC), orthodromically stimulate facial muscles and
      antidromically stimulate the facial nerve nucleus; this hyperexcitation
      continuously stimulates the facial muscles. These activated muscles can trigger
      somatosensory afferent skin nerve impulses and neuromuscular spindles from the
      trigeminal nerve, which, after transiting the Gasser ganglion and trigeminal
      nucleus, reach the somatosensory medial posterior ventral nucleus of the
      contralateral thalamus as well as the somatosensory cortical area of the face.
      Once activated, this area can stimulate the motor and supplementary motor areas
      (extrapyramidal and basal ganglia system), activating the motoneurons of the
      facial nerve nucleus and peripherally stimulating the facial muscles.
      CONCLUSIONS: We believe that bilateral MVD is the best approach in cases of BHFS.

PMID- 29026665
TI  - Lasting bilateral mydriasis after traumatic brain injury may not always be a lost
      case.
AB  - BACKGROUND: Lasting bilateral mydriasis and absence of pupillary light reflex
      following severe traumatic brain injury (TBI) are considered signs of
      irreversible brainstem damage and have been strongly associated with poor
      outcome. CASE DESCRIPTION: A young female patient presented with severe TBI,
      contusions, and diffuse brain edema. She was initially treated medically, but
      developed delayed secondary refractory intracranial hypertension and bilaterally
      dilated, non-reactive pupils for 12 h. Wide decompressive craniectomy and dural
      incisions were performed. The patient presented gradual improvement in her
      clinical condition [Glasgow Coma Scale (GCS) 13/15]. Delayed recurring infections
      lead to the patient's death due to sepsis after 3 months. CONCLUSION: In light of
      recent studies, lasting bilateral mydriasis may not always be considered a
      decisive factor for non-escalation of treatment, as variability among TBI
      patients and outcomes has been demonstrated. Wide decompressive craniectomy is
      viable for controlling refractory intracranial hypertension in hemodynamically
      stable patients.

PMID- 29026666
TI  - Bedside twist drill aspiration of cerebral abscess less than 2.5 cm in size: A
      case series and discussion.
AB  - BACKGROUND: Intracranial abscess remains a potentially deadly condition despite
      development of newer antibiotics and improved surgical methods. Many studies have
      evaluated the surgical indications for abscess drainage, and it has been
      generally accepted that intracranial abscesses greater than 2.5 cm may best be
      treated with surgical intervention followed by antibiotic therapy. More recently,
      studies have shown good results with stereotactic aspiration of abscesses to 1 cm
      in size. Furthermore, a recent case series in 2014 of 103 cases of bedside twist
      drill aspiration of cerebral abscess >2.5 cm showed a good recovery in 83.4% of
      cases. CASE DESCRIPTION: This case series examines the benefits of bedside twist
      drill aspiration of peripherally located brain abscess less than 2.5 cm in size.
      In our series, all patients were placed on broad-spectrum antibiotics and had
      negative blood and cerebrospinal fluid cultures. Our bedside biopsy resulted in
      de-escalation of antibiotics in 2 of the 3 patients and decreased hospital length
      of stay. CONCLUSION: In patients with peripherally located brain abscesses less
      than 2.5 cm in size, bedside twist drill drainage may be a safe and reasonable
      approach. Positive identification of infective pathogen allows for a decreased
      hospital length of stay and de-escalation of antibiotics regiment resulting in
      significant reduction of hospital costs and resources in 2 of the 3 patients
      treated. This is of benefit to the patient as well as the health system.

PMID- 29026667
TI  - Lumbar chronic subdural hematoma mimicking an intradural extramedullary tumor: A
      case report.
AB  - BACKGROUND: Chronic spinal subdural hematomas are extremely rare with only 28
      cases reported in the literature. Nevertheless, they should be considered among
      the differential diagnoses for spinal intradural/extramedullary lesions. CASE
      REPORT: A 65-year-old male presented with progressive back pain and right S1
      radiculopathy. Magnetic resonance imaging scan revealed a right-sided
      posterolateral intradural/extramedullary lesion at the L5-S1 level. It was
      hyperintense on T1 and hypointense on T2-weighted images; on the short TI
      inversion recovery sequence it was hyperintense. The lesion was excised through a
      right L5 hemilaminectomy, and the patient was neurologically intact
      postoperatively. Histopathology revealed a chronic subdural hematoma. CONCLUSION:
      Chronic spinal subdural hematoma can mimic intradural extramedullary spinal
      tumors even in the absence of trauma and/or coagulopathies.

PMID- 29026668
TI  - Fourth ventricle neurocysticercosis: Rigid endoscopic management. Description of
      direct transcerebellar approach.
AB  - BACKGROUND: Endoscopy has gained a crucial role in high specialty neurosurgery
      during the last decades. At present, there are well-defined flexible
      neuroendoscopic procedures to treat ventricular and subarachnoid space
      pathologies. Neurocysticercosis is recognized as a common cause of neurologic
      disease in developing countries and the United States. Surgical intervention,
      especially cerebrospinal fluid diversion, is the key for management of
      hydrocephalus. In 2002, a consensus suggested that ventricular forms should be
      treated with endoscopy as the first option. CASE DESCRIPTION: Here, we present
      the case of a 51-year-old right-handed male, from Estado de Mexico. Two days
      before admission he experienced holocraneal headache 7/10 on the visual analogue
      scale which was intermittent, with no response to any medication, sudden
      worsening of pain to 10/10, nausea, and vomit. On physical examination, he
      presented with 14 points in the Glasgow coma scale (M6, O4, V4), pupils were 3
      mm, there was adequate light-reflex response, and bilateral papilledema. The
      cranial nerves did not have other pathological responses, extremities had
      adequate strength of 5/5, and normal reflexes (++/++) were noted. Neuroimaging
      studies showed dilatation of the four ventricles as well as a cystic lesion in
      the fourth ventricle. Surgical position was Concorde, and the approach through a
      suboccipital burr hole was planned preoperatively with craneometric points. A
      rigid Karl Storz Hopkins II(r) endoscope was inserted directly through the
      cerebellum and the cystic lesion was extracted entirely. CONCLUSION: This article
      presents a useful technique with low morbidity and mortality. Further
      investigation is needed, especially in our Mexico, where neuroendoscopical
      techniques are still in the development phase.

PMID- 29026669
TI  - Factors predicting long-term outcome after short-segment posterior fixation for
      traumatic thoracolumbar fractures.
AB  - BACKGROUND: The "gold standard" for instrumentation of unstable thoracolumbar
      fracture-dislocations is pedicle screw and rod fixation. Although traditional
      treatment supports long-segment posterior fixation (LSPF), more recent studies
      show short-segment posterior fixation (SSPF) may be effective, but incur higher
      failure rates. Here, we evaluated the effectiveness of SSPF in the management of
      unstable thoracolumbar injuries and analyzed the factors impacting long-term
      outcomes. METHODS: In this retrospective analysis of 91 patients with
      thoracolumbar fractures managed with SSPF alone, we assessed the clinical and
      radiological parameters at preoperative, postoperative, and follow-up intervals
      along with reasons for failures of SSPF. RESULTS: We analyzed 91 patients (mean
      age: 33.5 years; Male: Female = 50:41) with thoracolumbar fractures treated with
      SSPF over a median follow-up period of 30 months. SSPF failures were observed in
      26 of 91 (28.6%) patients; the median time to implant failure was 17 months. On
      univariate analysis, statistically significant factors contributing to failure of
      SSPF included the presence of a burst fracture, a preoperative LSC (load-sharing
      classification) score >6, and translation/dislocation. With multinomial
      regression analysis, the only factor predictive for SSPF failure was the
      patients' postoperative ambulatory status. CONCLUSION: Patients with
      thoracolumbar facture dislocations, subjected to axial spinal loading
      postoperatively, should not be considered for SSPF alone. The following factors
      also contributed to SSPF failures: a burst fracture, a preoperative LSC score of
      >6, and/or presence of transverse dislocation.

PMID- 29026670
TI  - Rare case of conus medullaris glioblastoma multiforme in a teenager.
AB  - BACKGROUND: Primary intramedullary spinal glioblastoma multiforme (GBM) lesions
      are very rare comprising only 1.5% of all spinal cord tumors. These lesions
      typically result in rapid neurological deterioration and are associated with a
      very poor prognosis. CASE DESCRIPTION: A 16-year-old male exhibited a slowly
      progressive paraparesis with urinary incontinence, ultimately resulting in
      paraplegia. On magnetic resonance (MR), he was diagnosed with an intramedullary
      GBM of the spinal cord extending from the T9 level through the conus medullaris.
      Ten months following decompression/partial surgical resection of the
      intramedullary mass, he remained paraplegic. CONCLUSION: GBM of the spinal cord
      are rare in the pediatric age group. A 16-year-old male presented with a flaccid
      paraplegia attributed to an MR-documented GBM of the distal thoracic cord
      extending from the T9 level through the conus medullaris. Despite partial
      intramedullary tumor resection, 10 months postoperatively, he remained
      paraplegic.

PMID- 29026671
TI  - Bilateral caudate nucleus infarcts: A case report of a rare complication
      following endoscopic resection of a tuberculum sellae meningioma.
AB  - BACKGROUND: We present a rare complication of bilateral caudate infarcts and
      necrosed nasoseptal flaps after endoscopic transsphenoidal resection of
      tuberculum sellae meningioma. This case highlights the importance of early and
      accurate diagnosis and treatment of a postoperative cerebrospinal fluid (CSF)
      leak and associated bacterial meningitis, and reviews any existing guidelines
      regarding its management. CASE DESCRIPTION: A 54-year-old otherwise healthy man
      presented with progressive bitemporal hemianopsia. Magnetic resonance imaging of
      the head revealed a large, homogeneously enhancing sellar and suprasellar mass
      consistent with a meningioma. An endoscopic endonasal transsphenoidal approach
      was performed to resect the tuberculum sellae meningioma. The patient developed
      basal bacterial meningitis secondary to a CSF leak, requiring repair on two
      separate occasions. At the time of both repairs, there was evidence of necrosis
      of the nasoseptal flaps used for the repairs. Soon after the diagnosis of
      meningitis, the patient developed bilateral caudate infarcts. CONCLUSION: This
      report discusses the possible underlying etiologies for the bilateral caudate
      infarcts and necrosed flaps including bacterial meningitis with associated local
      vasospasm of nearby vessels resulting in infarction. This case emphasizes the
      importance of concise management of postendoscopic CSF leak and discusses the
      guidelines regarding antimicrobial therapy and the management of lumbar drains.

PMID- 29026672
TI  - Intraoperative navigation-guided resection of anomalous transverse processes in
      patients with Bertolotti's syndrome.
AB  - BACKGROUND: Bertolotti's syndrome is characterized by enlargement of the
      transverse process at the most caudal lumbar vertebra with a pseudoarticulation
      between the transverse process and sacral ala. Here, we describe the use of
      intraoperative three-dimensional image-guided navigation in the resection of
      anomalous transverse processes in two patients with Bertolotti's syndrome. CASE
      DESCRIPTIONS: Two patients diagnosed with Bertolotti's syndrome who had undergone
      the above-mentioned procedure were identified. The patients were 17- and 38-years
      old, and presented with severe, chronic low back pain that was resistant to
      conservative treatment. Imaging revealed lumbosacral transitional vertebrae at
      the level of L5-S1, which was consistent with Bertolotti's syndrome. Injections
      of the pseudoarticulations resulted in only temporary symptomatic relief. Thus,
      the patients subsequently underwent O-arm neuronavigational resection of the bony
      defects. Both patients experienced immediate pain resolution (documented on the
      postoperative notes) and remained asymptomatic 1 year later. CONCLUSION:
      Intraoperative three-dimensional imaging and navigation guidance facilitated the
      resection of anomalous transverse processes in two patients with Bertolotti's
      syndrome. Excellent outcomes were achieved in both patients.

PMID- 29026673
TI  - Endoscopic management of a cavernous malformation on the floor of third ventricle
      and aqueduct of Sylvius: Technical case report and review of the literature.
AB  - BACKGROUND: Intraventricular cavernous malformations are unusual intracranial
      vascular malformations; their deep anatomical location complicates their surgical
      management. Microsurgical approaches are the gold standard approaches for the
      resection of ventricular lesions, however, they imply considerable neurovascular
      risks. CASE DESCRIPTION: A 51-year-old patient presented with acute headache,
      diplopia, vertigo, blurred vision, and a depressed level of consciousness. A
      ventricular hemorrhage was treated with a ventriculostomy and the patient was
      discharged without hydrocephalus. After 11 days, he developed ataxia, diplopia,
      and a depressed level of consciousness. The patient was diagnosed with
      hydrocephalus secondary to the previous third ventricle hemorrhage. An endoscopic
      exploration using a 30 degrees  rigid ventricular endoscope was performed; after
      the third ventriculostomy, an intraventricular cavernous malformation located on
      the floor of the third ventricle and the aqueduct of Sylvius was resected.
      CONCLUSIONS: Three days after the surgery, magnetic resonance imaging
      demonstrated a gross total resection and adequate third ventriculostomy flow. One
      year after the surgery, the patient was asymptomatic. Neuroendoscopy has evolved
      towards minimally invasiveness, and in selected cases is an equally effective
      surgical approach to ventricular lesions. It provides minimal cerebral cortex
      disruption and vascular manipulation.

PMID- 29026674
TI  - Chronic headache caused by a titanium fixation plate: Report of two cases.
AB  - BACKGROUND: We report two patients with chronic postcraniotomy headache who
      showed rapid alleviation of pain after removal of titanium miniplates. CASE
      DESCRIPTION: (Case 1) A 26-year-old woman underwent a right frontal craniotomy
      and excision of the entire cerebral cavernous malformation. Eleven years later,
      she developed headache. The titanium plate was removed and the patient presented
      complete amelioration of headache. (Case 2) A 50-year-old man underwent an
      aneurysm clipping via the lateral supraorbital approach of the left side. One
      year later, he complained about throbbing pain. Removing the titanium plate led
      to complete relief of the headache. CONCLUSION: Titanium miniplate fixation may
      irritate the deep division of the supraorbital nerve and may cause a chronic
      headache. Here, we propound the idea that, postcraniotomy, titanium miniplates
      should not be placed above the temporal fusion line.

PMID- 29026675
TI  - Advantages of using a detachable-tip microcatheter and liquid embolic agents in
      the preoperative embolization of a recurrent cerebellar hemangioblastoma: A case
      report.
AB  - BACKGROUND: The preferred treatment for intracranial hemangioblastomas is
      surgical resection with or without preoperative embolization, however,
      embolization remains controversial due to risks such as distal tip entrapment,
      vascular injury during navigation, and embolic agent migration. CASE DESCRIPTION:
      A 54-year-old woman was admitted for surgical resection and preoperative
      embolization of a cerebellar hemangioblastoma. Although experience using Onyx
      with detachable and nondetachable tip microcatheters has been well reported in a
      variety of clinical circumstances, we describe the first case of a presurgical
      embolization of an intra-axial tumor using a second-generation detachable-tip
      microcatheter and a nonadhesive liquid embolic agent. Following the procedure, a
      nearly complete angiographic obliteration was achieved, as well as a successful
      subsequent surgical resection. CONCLUSION: Preoperative embolization with
      detachable-tip microcatheters and liquid embolic agents should be taken into
      consideration when assessing patients with hemangioblastomas of the posterior
      fossa due to the reduced risks of cardiac arrest, hemorrhage, and death.

PMID- 29026676
TI  - Spinal epidural abscess: Report on 27 cases.
AB  - BACKGROUND: Spinal epidural abscess, although an uncommon disease, often
      correlates with a high morbidity owing to significant delay in diagnosis.
      METHODS: In a prospective 5-year study, the clinical and magnetic resonance (MR)
      findings, treatment protocols, microbiology, and neurological outcomes were
      analyzed for 27 patients with spinal epidural abscess. RESULTS: Patients were
      typically middle-aged with underlying diabetes and presented with lumbar
      abscesses. Those undergoing surgical intervention >36 h after the onset of
      symptoms had poor neurological outcomes. CONCLUSION: Early recognition and timely
      evacuation of spinal abscesses minimized neurological morbidity and potential
      mortality.

PMID- 29026677
TI  - Bedside Ultrasound in the Diagnosis and Treatment of Children with Respiratory
      Difficulty Following Cardiac Surgery.
AB  - Many children frequently fail extubation or require a prolonged period of
      positive pressure ventilation support after cardiac surgery. Pediatric cardiac
      Intensive Care Unit (PCICU) ultrasound (US) stands as a simple, basic bedside
      tool that can be performed by trained intensivists for the diagnosis with
      immediate implication on therapeutic decisions in multiple scenarios that
      physicians may face in PCICU. Bedside US is widely available, convenient, and
      inexpensive. This educational article based mainly on our own experience is
      highlighting the role of US in detecting the most common causes of respiratory
      weaning difficulties and extubation failure in postoperative cardiac children
      through proposed illustration and algorithm.

PMID- 29026678
TI  - Statistical model for OCT image denoising.
AB  - Optical coherence tomography (OCT) is a non-invasive technique with a large array
      of applications in clinical imaging and biological tissue visualization. However,
      the presence of speckle noise affects the analysis of OCT images and their
      diagnostic utility. In this article, we introduce a new OCT denoising algorithm.
      The proposed method is founded on a numerical optimization framework based on
      maximum-a-posteriori estimate of the noise-free OCT image. It combines a novel
      speckle noise model, derived from local statistics of empirical spectral domain
      OCT (SD-OCT) data, with a Huber variant of total variation regularization for
      edge preservation. The proposed approach exhibits satisfying results in terms of
      speckle noise reduction as well as edge preservation, at reduced computational
      cost.

PMID- 29026679
TI  - sideSPIM - selective plane illumination based on a conventional inverted
      microscope.
AB  - Previously described selective plane illumination microscopy techniques typically
      offset ease of use and sample handling for maximum imaging performance or vice
      versa. Also, to reduce cost and complexity while maximizing flexibility, it is
      highly desirable to implement light sheet microscopy such that it can be added to
      a standard research microscope instead of setting up a dedicated system. We
      devised a new approach termed sideSPIM that provides uncompromised imaging
      performance and easy sample handling while, at the same time, offering new
      applications of plane illumination towards fluidics and high throughput 3D
      imaging of multiple specimen. Based on an inverted epifluorescence microscope,
      all of the previous functionality is maintained and modifications to the existing
      system are kept to a minimum. At the same time, our implementation is able to
      take full advantage of the speed of the employed sCMOS camera and piezo stage to
      record data at rates of up to 5 stacks/s. Additionally, sample handling is
      compatible with established methods and switching magnification to change the
      field of view from single cells to whole organisms does not require labor
      intensive adjustments of the system.

PMID- 29026680
TI  - All-optical photoacoustic projection imaging.
AB  - We introduce all-optical photoacoustic projection imaging. An array of fiber
      optic interferometers is used to measure photoacoustic signals. The obtained
      images represent the projection of the three-dimensional spatial light absorbance
      within a sample onto a two-dimensional plane. We assess the performance of the
      system by phantom measurements and show that the fiber-optic detectors achieve a
      noise-equivalent pressure of 24 Pascal at a 10 MHz bandwidth. Furthermore, we
      demonstrate the ability to acquire high-resolution projection images of large
      volumes within a short period of time.

PMID- 29026681
TI  - Resolving adjacent nanophosphors of different concentrations by excitation-based
      cone-beam X-ray luminescence tomography.
AB  - Cone-beam X-ray luminescence computed tomography (CB-XLCT) has been proposed as a
      new molecular imaging modality recently. It can obtain both anatomical and
      functional tomographic images of an object efficiently, with the excitation of
      nanophosphors in vivo or in vitro by cone-beam X-rays. However, the ill-posedness
      of the CB-XLCT inverse problem degrades the image quality and makes it difficult
      to resolve adjacent luminescent targets with different concentrations, which is
      essential in the monitoring of nanoparticle metabolism and drug delivery. To
      address this problem, a multi-voltage excitation imaging scheme combined with
      principal component analysis is proposed in this study. Imaging experiments
      performed on physical phantoms by a custom-made CB-XLCT system demonstrate that
      two adjacent targets, with different concentrations and an edge-to-edge distance
      of 0 mm, can be effectively resolved.

PMID- 29026682
TI  - Wavelength-dependent optical properties of melanosomes in retinal pigmented
      epithelium and their changes with melanin bleaching: a numerical study.
AB  - In this paper, we present the first numerical study on full metrics of wavelength
      dependent optical properties of melanosomes in retinal pigmented epithelial (RPE)
      cells. T-matrix method was used to simulate the spheroidal shapes of mature
      melanosomes, and the complex refractive index was calculated by a subtractive
      Kramers-Kronig relation for melanin. The validity of the method was first
      confirmed by Mie theory, and corroborated by a comparison between visible light
      and near infrared (NIR) optical coherence tomography (OCT) on human retinal
      imaging. We also studied the changes of melanosome optical properties due to
      melanin bleaching by numerically reducing the absorption of melanin. This study
      implies a unique approach to detect melanin changes specifically in RPE by a
      spectroscopic contrast of optical coherence tomography.

PMID- 29026683
TI  - High sensitivity optical measurement of skin gloss.
AB  - We demonstrate a low-cost optical method for measuring the gloss properties with
      improved sensitivity in the low gloss regime, relevant for skin gloss properties.
      The gloss estimation method is based on, on the one hand, the slope of the
      intensity gradient in the transition regime between specular and diffuse
      reflection and on the other on the sum over the intensities of pixels above
      threshold, derived from a camera image obtained using unpolarized white light
      illumination. We demonstrate the improved sensitivity of the two proposed methods
      using Monte Carlo simulations and experiments performed on ISO gloss calibration
      standards with an optical prototype. The performance and linearity of the method
      was compared with different professional gloss measurement devices based on the
      ratio of specular to diffuse intensity. We demonstrate the feasibility for in
      vivo skin gloss measurements by quantifying the temporal evolution of skin gloss
      after application of standard paraffin cream bases on skin. The presented method
      opens new possibilities in the fields of cosmetology and dermatopharmacology for
      measuring the skin gloss and resorption kinetics and the pharmacodynamics of
      various external agents.

PMID- 29026684
TI  - Combined multi-distance frequency domain and diffuse correlation spectroscopy
      system with simultaneous data acquisition and real-time analysis.
AB  - Frequency domain near infrared spectroscopy (FD-NIRS) and diffuse correlation
      spectroscopy (DCS) have emerged as synergistic techniques for the non-invasive
      assessment of tissue health. Combining FD-NIRS oximetry with DCS measures of
      blood flow, the tissue oxygen metabolic rate can be quantified, a parameter more
      closely linked to underlying physiology and pathology than either NIRS or DCS
      estimates alone. Here we describe the first commercially available integrated
      instrument, called the "MetaOx", designed to enable simultaneous FD-NIRS and DCS
      measurements at rates of 10 + Hz, and offering real-time data evaluation. We show
      simultaneously acquired characterization data demonstrating performance
      equivalent to individual devices and sample in vivo measurements of pulsation
      resolved blood flow, forearm occlusion hemodynamic changes and muscle oxygen
      metabolic rate monitoring during stationary bike exercise.

PMID- 29026685
TI  - Pharmacokinetics of carfilzomib in patients with advanced malignancies and
      varying degrees of hepatic impairment: an open-label, single-arm, phase 1 study.
AB  - BACKGROUND: Carfilzomib is approved in the United States and Europe for treatment
      of relapsed or refractory multiple myeloma (MM). This study evaluated
      pharmacokinetics (PK) and safety of carfilzomib in patients with relapsed or
      progressive advanced malignancies and varying degrees of impaired hepatic
      function. METHODS: Patients with normal hepatic function (normal) or hepatic
      impairment (mild, moderate, or severe) received carfilzomib infusion in 28-day
      cycles. The primary objective was to assess the influence of hepatic impairment
      on carfilzomib PK following 27 and 56 mg/m2 doses. RESULTS: The majority of
      patients enrolled in this study had solid tumors (n = 44) vs. MM (n = 2) since
      patients with multiple myeloma do not tend to have severe hepatic impairment in
      the same way as patients with solid tumors. A total of 11 normal and 17 mild, 14
      moderate, and 4 severe hepatic impairment patients were enrolled. Compared with
      patients with normal hepatic function, patients with mild and moderate hepatic
      impairment had 44 and 26% higher carfilzomib AUC0-last, respectively (27 mg/m2
      dose); increases at the 56 mg/m2 dose were 45 and 21%, respectively. Considerable
      PK variability (% coefficient of variation in AUC <=100%) was discerned and no
      consistent trend of increasing exposure resulting from increasing hepatic
      impairment severity (moderate vs. mild) was seen. The observed adverse event (AE)
      profile in patients of mostly solid tumors was consistent with the known safety
      profile of carfilzomib, with the exception of an increased frequency of AEs
      consistent with hepatic function abnormalities. CONCLUSIONS: In this population
      of primarily advanced solid tumor patients, patients with mild and moderate
      hepatic impairment had approximately 20-50% higher carfilzomib AUC vs. normal
      hepatic function patients. These increases are unlikely to be clinically
      significant, in light of the intrinsic PK variability and exposure-response
      relationship of carfilzomib. Trial registration http://clinicaltrials.gov
      NCT01949545; date of registration: September 6, 2013.

PMID- 29026687
TI  - Ascendobifemoral Bypass for the Treatment of a Thoracic Endograft Infection.
AB  - Background  Endograft infections (EIs) are rare complications after endovascular
      procedures in the thoracic and abdominal aortas. The challenging treatment
      encloses antibiotic and surgical therapies. Case Description  A 74-year-old male
      patient developed an EI after an endovascular procedure (thoracic endovascular
      aortic repair [TEVAR]). Despite a long-term oral antibiotic therapy, the clinical
      symptoms showed no falling trend. Because of the expanded infection from above
      the celiac trunk up to the aortic arch, we decided to remove the infected
      endograft and to implant an extra-anatomic ascendobifemoral bypass. Conclusion 
      The implantation of an ascendobifemoral bypass was a successful treatment option
      for EIs after TEVAR.

PMID- 29026686
TI  - Pain Prediction From ECG in Vascular Surgery.
AB  - Varicose vein surgeries are routine outpatient procedures, which are often
      performed under local anaesthesia. The use of local anaesthesia both minimises
      the risk to patients and is cost effective, however, a number of patients still
      experience pain during surgery. Surgical teams must therefore decide to
      administer either a general or local anaesthetic based on their subjective
      qualitative assessment of patient anxiety and sensitivity to pain, without any
      means to objectively validate their decision. To this end, we develop a 3-D
      polynomial surface fit, of physiological metrics and numerical pain ratings from
      patients, in order to model the link between the modulation of cardiovascular
      responses and pain in varicose vein surgeries. Spectral and structural complexity
      features found in heart rate variability signals, recorded immediately prior to
      17 varicose vein surgeries, are used as pain metrics. The so obtained pain
      prediction model is validated through a leave-one-out validation, and achieved a
      Kappa coefficient of 0.72 (substantial agreement) and an area below a receiver
      operating characteristic curve of 0.97 (almost perfect accuracy). This proof-of
      concept study conclusively demonstrates the feasibility of the accurate
      classification of pain sensitivity, and introduces a mathematical model to aid
      clinicians in the objective administration of the safest and most cost-effective
      anaesthetic to individual patients.

PMID- 29026689
TI  - Accurate diagnosis of prenatal cleft lip/palate by understanding the embryology.
AB  - Cleft lip with or without cleft palate (CP) is one of the most common congenital
      malformations. Ultrasonographers involved in the routine 20-wk ultrasound
      screening could encounter these malformations. The face and palate develop in a
      very characteristic way. For ultrasonographers involved in screening these
      patients it is crucial to have a thorough understanding of the embryology of the
      face. This could help them to make a more accurate diagnosis and save time during
      the ultrasound. Subsequently, the current postnatal classification will be
      discussed to facilitate the communication with the CP teams.

PMID- 29026690
TI  - Pancreatic imaging: Current status of clinical practices and small animal
      studies.
AB  - Different causative factors acting on the pancreas can result in diseases such as
      pancreatitis, diabetes and pancreatic tumors. The high incidence and mortality of
      pancreatic diseases have placed diagnostic imaging in a crucial position in daily
      clinical practice. In this mini-review article different pancreatic imaging
      techniques are discussed, from the standard clinical imaging modalities and state
      of the art clinical magnetic resonance imaging techniques to current situations
      in pre-clinical pancreatic imaging studies. In particular, the challenges of pre
      clinical rodent pancreatic imaging are addressed, with both the image acquisition
      techniques and the post-processing methods for rodent pancreatic imaging
      elaborated.

PMID- 29026691
TI  - Accuracy of crescent sign on ocular ultrasound in diagnosing papilledema.
AB  - AIM: To study the usefulness of orbital ultrasonography in the diagnosis of
      papilledema. METHODS: Fifty patients who were referred to the neurophthalmology
      clinic and clinically suspected to have papilledema were selected. Thorough,
      clinical examination with slitlamp biomicroscopy and visual acuity assessment was
      done. These patients underwent ultrasonography to demonstrate the crescent sign.
      The patients were further evaluated with the neurologist and magnetic resonance
      imaging (MRI) thus confirming the diagnosis of papilledema. The results of our
      ultrasonographic evaluation were correlated with final diagnosis after thorough
      clinical evaluation, imaging and the neurologist's opinion. RESULTS: Out of 50
      patients diagnosed having papilledema on MRI, 46 (92%) showed crescent sign on B
      scan ultrasonography. Headache was most common presenting complaint in 47 (94%)
      and idiopathic intracranial hypertension was most common underlying cause of
      papilledema in 30 (60%) cases. CONCLUSION: "Crescent sign" seen on
      ultrasonography is a sensitive tool for diagnosis of papilledema. It is cost
      effective, less cumbersome and effective tool to differentiate between
      papilledema and pseudo papilledema before subjecting the patients to costly
      investigations like MRI. A positive crescent sign should always be followed by
      MRI to find out the cause of papilledema.

PMID- 29026692
TI  - A Systematic Review of the Consequences of Early Extraction of First Permanent
      First Molar in Different Mixed Dentition Stages.
AB  - AIMS AND OBJECTIVES: The aim of this study was to consider the available evidence
      regarding early extraction of permanent first molars (PFMs) in different mixed
      dentition stages that affect the integrity of occlusion and the implications for
      treatment planning. MATERIALS AND METHODS: Electronic database, including PubMed
      and Science Direct, searches were conducted for available evidence. Key terms
      used in the search were "extraction," " first permanent molar," and "mixed
      dentition." RESULTS: The initial search identified 56 studies to be related to
      the review. Although a significant number of published articles had dealt with
      early extraction of PFM, only three studies had fulfilled the final selection
      criteria to be considered for this systematic review. CONCLUSION: Future active
      appliance treatment is important after extraction of PFMs with poor prognosis. If
      such therapy is not needed, consideration should be given to extraction at the
      ideal developmental age to achieve spontaneous space closure. Each case should be
      assessed for the need of balancing or compensating extractions to preserve the
      dental midline and prevent overeruption.

PMID- 29026693
TI  - Platelet-rich Fibrin: A Paradigm in Periodontal Therapy - A Systematic Review.
AB  - Periodontal tissue regeneration has always been a challenge for the periodontists
      owing to its structural complexity. Although with tissue engineering as a growing
      multidisciplinary field, this aim has partially been fulfilled. In recent years,
      platelet-rich fibrin (PRF) has gained wide attention for its utilization as a
      biocompatible regenerative material not only in dental but also in medical
      fields. The following systematic review has gathered all the currently available
      in vitro, animal, and clinical studies utilizing PubMed electronic database from
      January 2006 to August 2016 highlighting PRF for soft and hard tissue
      regeneration and/or wound healing. Although results are encouraging but require
      further validation from clinical studies to justify the potential role of PRF in
      periodontal regeneration so that this relatively inexpensive autologous
      biomaterial can be utilized at a wider scale.

PMID- 29026694
TI  - A Systematic Review and Meta-analysis of School Children's Caries Studies in Gulf
      Cooperation Council States.
AB  - OBJECTIVES: The aim of the present study was to evaluate the prevalence and
      severity of dental caries school children in the Gulf Cooperation Council (GCC)
      area, to help the development of systematic approaches for preventive oral care
      programs in the GCC states and to provide sound information for oral health
      promotion and public health care. MATERIALS AND METHODS: A comprehensive search
      to identify both published and unpublished articles concerning relevant studies
      of dental caries in children aged 6-16 years for their permanent teeth published
      from 1992 to 2016 with no language and time limit was performed. The search
      strategies employed electronic databases and incorporated both dental subject
      headings and free-text term. RESULTS: The overall mean decayed, missing and
      filled teeth in the permanent teeth was 2.57, and the prevalence was 64.7% in the
      GCC area. CONCLUSIONS: Most of the studies were conducted in the Kingdom of Saudi
      Arabia. The results may not be a true reflection, and other countries in GCC are
      urged to study the prevalence and severity of caries in their children
      population.

PMID- 29026695
TI  - Comparison Between Antibacterial Effect of Chlorhexidine 0.2% and Different
      Concentrations of Cyperus rotundus Extract: An In vitro Study.
AB  - AIMS AND OBJECTIVES: Modern methods of caries prevention concentrated on natural
      ingredients usage such as probiotics and polyphenols that are safer for young
      children with Streptococcus mutans inhibitory properties. The purpose of this
      study was to compare antibacterial effects of different concentration of Cyperus
      rotundus extract and chlorhexidine (CHX) 0.2% mouthwash on S. mutans and
      Lactobacillus acidophilus. MATERIALS AND METHODS: In this in vitro study, the
      antibacterial effectiveness of the C. rotundus extract and CHX was compared with
      minimum inhibitory concentration (MIC) test in tube, minimum bactericidal
      concentration (MBC) test in solid medium, and disc diffusion for measurement of
      inhibition zone. Data were analyzed using one-way ANOVA, one sample t-test, and
      independent sample t-test statistical methods by SPSS. 24 software (SPSS Inc.,
      Chicago, USA). RESULTS: MIC and MBC values of the C. rotundus extract were
      obtained 225 and 450 mg/ml, respectively, for S. mutans and 108 and 225 mg/ml for
      L. acidophilus, which are more than CHX (0.5, 1 res.). The inhibition zone
      increased in a dose-dependent manner but lower than CHX. CONCLUSION: The C.
      rotundus extract had antibacterial effects (bactericide and bacteriostatic) on S.
      mutans and L. acidophillus. Although this effect was lower than CHX. With regard
      to adverse effect of CHX, this extract can be a potential antibacterial agent.

PMID- 29026688
TI  - Establishing the presence or absence of chronic kidney disease: Uses and
      limitations of formulas estimating the glomerular filtration rate.
AB  - The development of formulas estimating glomerular filtration rate (eGFR) from
      serum creatinine and cystatin C and accounting for certain variables affecting
      the production rate of these biomarkers, including ethnicity, gender and age, has
      led to the current scheme of diagnosing and staging chronic kidney disease (CKD),
      which is based on eGFR values and albuminuria. This scheme has been applied
      extensively in various populations and has led to the current estimates of
      prevalence of CKD. In addition, this scheme is applied in clinical studies
      evaluating the risks of CKD and the efficacy of various interventions directed
      towards improving its course. Disagreements between creatinine-based and cystatin
      based eGFR values and between eGFR values and measured GFR have been reported in
      various cohorts. These disagreements are the consequence of variations in the
      rate of production and in factors, other than GFR, affecting the rate of removal
      of creatinine and cystatin C. The disagreements create limitations for all eGFR
      formulas developed so far. The main limitations are low sensitivity in detecting
      early CKD in several subjects, e.g., those with hyperfiltration, and poor
      prediction of the course of CKD. Research efforts in CKD are currently directed
      towards identification of biomarkers that are better indices of GFR than the
      current biomarkers and, particularly, biomarkers of early renal tissue injury.

PMID- 29026697
TI  - Effect of Fluoride Concentration in Drinking Water on Intelligence Quotient of 12
      14-Year-Old Children in Mathura District: A Cross-Sectional Study.
AB  - AIMS: The aim was to assess and correlate the influence of the concentration of
      fluoride in ingested water on the intelligence quotient (IQ) of 12-14-year-old
      youngsters in Mathura district. MATERIALS AND METHODS: A total of 219 children
      were selected, 75 from low F area, 75 medium F area, and 69 from high F area. The
      concentration of fluoride in the routinely ingested water was estimated using
      "Ion Selective Electrode method"; then, Raven's Test was utilized to estimate the
      IQ of the study participants. Independent t-test, Tukey's post hoc, Chi-square an
      analysis of variance tests were used to associate the mean and proportion IQ
      scores in high-, medium-, and low-fluoride regions along with inter-group
      significant differences (P <= 0.05). RESULTS: The comparison of IQ score showed
      that 35 (46.7%) participants from the high fluoride and 10 (13.3%) participants
      from the medium-fluoride areas had below average IQ. Further, it was noted that
      the lowest mean marks were obtained by the children in the high-fluoride region
      (13.9467) followed by those in medium (18.9467) and uppermost in least noted
      fluoride area (38.6087). However, gender-based intergroup comparison did not
      produce a significant relation with fluoride (P >= 0.05). CONCLUSION:
      Concentration of Fluoride in the ingested water was significantly associated with
      the IQ of children. It has also coined the proportional variability in mental
      output in accordance to the ingested fluoride level. As two sides of a coin,
      fluoride cannot be utterly blamed for a lower intelligence in a population; it
      puts forward a fact that intelligence is a multifactorial variable with a
      strategic role played by genetics and nutrition to develop cognitive and
      psychosomatic activities in an individual.

PMID- 29026696
TI  - The Effect of Chlorhexidine Mixed with Mineral Trioxide Aggregate on Bacterial
      Leakage of Apical Plug in Simulated Immature Teeth Using Human Fresh Saliva.
AB  - OBJECTIVES: Apexification is a challenging treatment in necrotic open apices
      teeth and bacterial leakage is the main reason for the treatment failure. The aim
      of this study is to compare the effect of mixing mineral trioxide aggregate (MTA)
      with chlorhexidine (CHX) on microbial leakage in apexification treatment of
      simulated immature teeth. MATERIALS AND METHODS: In this experimental study, 44
      intact central incisors were selected based on inclusion criteria. The coronal
      and 2 mm of apical part of the specimens were removed till all root segments were
      12 mm long. The apical parts of the teeth were prepared using Profile #40/0.06
      (Dentsply Maillefer, Ballaigues, Switzerland) in the apical to coronal direction
      to simulate open apices. The specimens were separated into experimental groups (n
      = 40) and control groups (n = 4). Group 1 delivered a 5 mm apical plug by MTA/H2O
      and group 2 delivered an apical plug by MTA/CHX 0.12%. The positive control group
      had no apical barrier; on the other hand, the negative control group had an
      apical barrier and two layers of nail varnish on entire root surface. The
      microbial leakage assessment was done by a dual-chamber apparatus using fresh
      human saliva after 10-week follow-up. The turbidity of the lower chamber
      containing the Brain Heart Infusion (BHI) solution was analyzed based on the
      McFarland (0.5) standard which utilizes spectrophotometry results. Data analyses
      were done using Chi-square, Kaplan-Meier, and log-rank tests. RESULTS: MTA/CHX
      group had lower microbial leakage percentage (P = 0.001) and longer time of
      leakage (P = 0.002) in compared with MTA/H2O group and the difference was
      statistically meaningful. CONCLUSION: Based on the results of this study, MTA/CHX
      mixture can reduce the amount of bacterial leakage.

PMID- 29026698
TI  - Evaluation of the Impact of Oral Health Education on Oral Hygiene Knowledge and
      Plaque Control of School-going Children in the City of Amritsar.
AB  - AIMS AND OBJECTIVES: The present study aims to evaluate the impact of oral health
      education on oral hygiene knowledge and plaque control of school-going children
      in the city of Amritsar. MATERIALS AND METHODS: The study was carried out for 6
      weeks and included four groups of schoolchildren of 10-12 years of age. Children
      were randomly selected and assigned into one of the four groups - Group I (verbal
      communication), Group II (verbal communication and self-educational pamphlets),
      Group III (audiovisual aids and verbal communication), and Group IV (control
      group). Oral health education was assessed by getting a questionnaire filled by
      children and plaque scores was recorded using Silness and Loe plaque index before
      and after the study. The data were then compared and analyzed using SPSS 16
      software manufactured by IBM. RESULTS: Differences in knowledge gain after the
      dental health education were statistically significant between all the groups,
      except between Group II and Group III in which the difference was not found to be
      significant. Group III showed the highest decrease in plaque score followed by
      Group II. There was a significant difference in reduction in plaque scores
      between all the groups, except between the Groups II and III. CONCLUSION: Both
      methods, i.e., pamphlets and audiovisual aids when used along with oral lectures,
      are equally effective in improving the knowledge and plaque scores in children.

PMID- 29026699
TI  - Comparison of the Clinical Biological Width with the Published Standard
      Histologic Mean Values.
AB  - AIMS AND OBJECTIVES: Biologic width (BW) as defined by Cohen is the part of the
      supracrestal gingival tissues that occupy the space between the base of the
      gingival crevice and the alveolar crest; it includes the junctional epithelium
      and the connective tissue element. Interactions between dental crowns and the
      marginal periodontal tissues analyzed in many review papers concluded that the
      recognition of the BW, in terms of crown margin placement, is beneficial for
      periodontal health. Therefore, knowledge of the dimensions of the sum of the
      junctional epithelium and connective tissue attachment as well as the sulcus
      depth (SD) is of clinical relevance. The aim of the study is to compare the
      average SD and BW clinically measured around teeth with the standard application
      of a mean value of 0.69 mm and 2.04 mm, respectively, found by Gargiulo et al.in
      a histological study on cadavers. MATERIALS AND METHODS: Forty-two healthy
      patients with age ranging from 20 to 50 years presented to the Multidisciplinary
      Department at the Lebanese University. A total of 504 tooth sites of 126 teeth
      were selected and measured by two periodontists. All measurements were done on
      teeth requiring infiltration anesthesia for surgical, restorative, or endodontic
      procedures on neighboring tooth/teeth, which eliminate any ethical concerns. The
      SD and the distance from gingival margin to bone crest at four sites per tooth;
      mesial, midbuccal, distal, and midlingual/palatal were measured. Clinical, BW was
      calculated by subtracting SD from the distance between gingival margin to bone
      crest. STATISTICAL ANALYSIS: Friedman's ANOVA test, independent samples t-tests,
      and one-sample t-tests were applied. The IBM(r) SPSS(r) statistics 20.0
      statistical package was used to carry out all statistical analyses. RESULTS: The
      BW is statistically significantly lower than the value stated by Gargiulo et al.
      (2.04 mm) with a mean value of 1.13 mm, whereas the SD is statistically
      significantly greater than the value stated by Gargiulo et al. (0.69 mm) with a
      mean value of 1.96 mm. CONCLUSION: It can be concluded that there is a need to
      create a patient/site-specific distance from the proposed margin of the
      restoration to the bone crest when restoring subgingivally fractured or carious
      teeth. This leads to more stable and healthy tissues when performing crown
      lengthening procedures. Therefore, using the term clinical, BW is more reliable
      and it should be used to reestablish stability and integrity of periodontal
      tissues around restored teeth.

PMID- 29026700
TI  - Relationship Between the Remaining Dentin Thickness and Coronal Pulp Status of
      Decayed Primary Molars.
AB  - AIMS AND OBJECTIVES: The aim of this study was to assess the correlation between
      the remaining dentin thickness (RDT) in deep decayed primary molars and the
      inflammatory status and bacterial composition of the corresponding coronal pulp.
      We hypothesized that RDT could be used as a reference for clinicians in assigning
      the indication for pulpotomy. MATERIALS AND METHODS: Pulpotomies were conducted
      on the cameral pulp of 48 primary molars. Microorganisms, such as Lactobacillus
      sp., Streptococcus sp., and Prevotella sp., were identified and quantified and
      levels of tumor necrosis factor-alpha (TNF-alpha) and interlukin-6 (IL-6) were
      assessed. The correlation between the pre-operative RDT based on radiographic
      images and inflammatory-microbial profiles in vitro was evaluated using
      Spearman's rho correlation coefficient. All data analysis was performed using a
      statistical software program (SPSS 20.0, SPSS Inc., Chicago, IL, USA). RESULTS:
      Immunological and microbiological studies revealed elevated levels of TNF-alpha
      and IL-6 cytokines, and Lactobacillus sp., Streptococcus sp. and Prevotella sp.
      in the cameral pulp with an RDT measuring up to 1.1 mm. No significant
      relationship could be established between RDT, inflammatory status and microbial
      content of the pulps. CONCLUSION: The RDT remains a key clinical factor that
      needs to be assessed when establishing the indication for pulpotomy. Additional
      parameters that can improve this therapy should be investigated in the future.

PMID- 29026701
TI  - How Much Do Italian Patients in Supportive Periodontal Therapy Know about the
      Role of Smoking in Oral Health and What is Their Lifestyle?
AB  - OBJECTIVE: The level of awareness of patients receiving supportive periodontal
      therapy (SPT) concerning the role of smoking as a risk factor for oral health was
      investigated. MATERIALS AND METHODS: A questionnaire was administered to 158
      patients previously treated for periodontitis in four periodontally oriented
      private dental offices in Rome. The generalized linear model was used to test the
      simultaneous effect of questions posed to all patients. Fisher's exact test was
      used to verify significant associations among qualitative variables. RESULTS:
      Only 53.79% of the total sample referred having been informed by the
      dentist/hygienist about smoking as an oral health risk factor. About 40% of
      patients did not know that oral cancer exists and only 36.08% of them reported
      being informed about it by their own dentist/hygienist. Females are significantly
      less frequent among ex-smokers than among smokers. Nonsmokers were on periodontal
      supportive therapy for a longer period than smokers. Patients who started smoking
      later found harder to quit smoking than those who started earlier. CONCLUSION:
      Awareness of patients in SPT about health risks related to smoking does not
      assume a change in their harmful behavior. Among oral health professionals, there
      is not yet a widespread awareness of the importance of their role in increasing
      patient's motivation to quit.

PMID- 29026702
TI  - Apical Extrusion of Intracanal Bacteria with Single File and Multifile Rotary
      Instrumentation Systems.
AB  - AIMS AND OBJECTIVES: Instrumentation techniques may cause extrusion of
      microorganisms and their products into the periapical region resulting
      inflammation and treatment failure. The aim of this ex vivo study was comparing
      the apical bacterial extrusion in canals prepared with single file versus
      multiple file rotary systems. MATERIALS AND METHODS: Ninety-two human single
      rooted mandibular first premolars were used. Endodontic access cavities were
      prepared, and root canals were contaminated with an Enterococcus faecalis (E.
      faecalis) suspension. The samples were incubated at 37 degrees C for 30 days; the
      contaminated teeth were divided into four groups of 20 specimens each (1:
      Reciproc, 2: Mtwo, 3: Neoniti A1, 4: Safesider). Six teeth were not infected and
      each were prepared with one of the above instruments were considered as negative
      and six teeth which had been previously infected, were used as positive control
      groups. Extruded bacteria from the apical foramen during instrumentation were
      collected into vials containing 0.9% NaCl. The microbial samples were taken from
      the vials and incubated in brain heart agar medium for 24 h. The resulting
      bacterial titer, in colony-forming units per mL, was determined. The data entered
      into SPSS 18 software and were analyzed by Kruskal-Wallis and Mann-Whitney U
      tests at 0.05 significance level. RESULTS: Mtwo multifile system showed
      significantly less bacterial extrusion than Safesider (P = 0.015) and Neoniti A1
      (P = 0.042) but did not show significant difference with Reciproc system (P =
      0.25). CONCLUSIONS: All instrumentation systems extruded bacteria beyond the
      apical foramen. However, this study showed that Mtwo multifile rotary system
      extruded fewer bacteria.

PMID- 29026703
TI  - Endodontic Management of a Maxillary First Molar with Seven Root Canal Systems
      Evaluated Using Cone-Beam Computed Tomography Scanning.
AB  - Permanent maxillary first molar morphology has been studied widely. Usually, it
      has three roots with three canals and the frequent deviation being incidence of a
      second mesiobuccal canal, thus showing a multifaceted root canal anatomy. Other
      variations comprise four and five roots and abnormal root canal morphology within
      individual roots. Many case reports with five and six root canals or a C-shaped
      canal configuration have been reported in the past. This varying number of root
      canals poses a challenge for endodontist in detecting and treating by root canal
      treatment. This problem can be avoided using techniques such as using the dental
      operating microscope and cone-beam computed tomography (CBCT). We report a change
      in canal morphology case of maxillary first molar having seven root canals, its
      evaluation, and management using latest equipment such as CBCT.

PMID- 29026704
TI  - Therapeutic Inhibitors against Mutated BRAF and MEK for the Treatment of
      Metastatic Melanoma.
AB  - Melanoma is one of the most aggressive cancers in the world and is responsible
      for the majority of skin cancer deaths. Recent advances in the field of
      immunotherapy using active, adoptive, and antigen-specific therapeutic
      approaches, have generated the expectation that these technologies have the
      potential to improve the treatment of advanced malignancies, including melanoma.
      Treatment options for metastatic melanoma patients have been dramatically
      improved by the FDA approval of new therapeutic agents including vemurafenib,
      dabrafenib, and sorafenib. These kinase inhibitors have the potential to work in
      tandem with MEK, PI3K/AKT, and mTOR to inhibit the activity of melanoma inducing
      BRAF mutations. This review summarizes the effects of the new therapeutic agents
      against melanoma and the underlying biology of these BRAF inhibitors.

PMID- 29026705
TI  - Role of Recepteur D'origine Nantais on Gastric Cancer Development and
      Progression.
AB  - Recepteur d'origine nantais (RON) is a receptor tyrosine kinase belonging to the
      subfamily of which c-MET is the prototype. Large epidemiologic studies have
      confirmed the strong association between RON and gastric cancer development.
      Constitutive activation of RON signaling directly correlates with tumorigenic
      phenotypes of gastric cancer and a poor survival rate in advanced gastric cancer
      patients. In this review, we focus on recent evidence of the aberrant expression
      and activation of RON in gastric cancer tumors and provide insights into the
      mechanism of RON signaling associated with gastric cancer progression and
      metastasis. Current therapeutics against RON in gastric cancer are summarized.

PMID- 29026706
TI  - Development of Novel Drug-Eluting Stents for Acute Myocardial Infarction.
AB  - Delayed arterial healing at culprit sites after drug-eluting stent (DES)
      placement for acute myocardial infarction (AMI) is associated with increased risk
      of late stent thrombosis. The Korea Acute Myocardial Infarction Registry was
      established in commemoration of the 50th anniversary of Korea Circulation
      Society. Between November 2005 and December 2016, more than 62,000 patients were
      registered from 50 primary percutaneous coronary intervention (PCI) centers in
      Korea. DES in AMI may be safe and effective, however, there is concern about
      increased stent thrombosis after DES implantation in AMI patients, requiring
      longer-term dual anti-platelet therapy to reduce the risk of late stent
      thrombosis. Device innovation is needed to overcome issues such as stent
      thrombosis and restenosis by using new coating materials with biocompatible
      polymers, different coating methods using non-polymer techniques, bioabsorbable
      stents and pro-healing stents. In this review article, we describe the current
      usage of DES in AMI in Korea and introduce novel DES uses in development for
      patients with AMI. We have developed many types of DES in our research
      laboratory. Abciximab-coated stents inhibited platelet thrombi and restenosis.
      Furthermore, anti-oxidants (carvedilol, probucol and alpha-lipoic acid) were used
      for stent coating. Currently we are developing novel DESs using polymer-free and
      natural binding techniques, peptide coating stents, gene-and-drug delivery,
      bioabsorbable stents using 3D printing, endothelial progenitor cell capturing
      stents to promote reendothelialization and reduce stent thrombosis. New DESs in
      development may be safe and effective in preventing late stent thrombosis and
      restenosis in patients with AMI.

PMID- 29026707
TI  - NADPH Oxidase Mediates beta-Amyloid Peptide-Induced Neuronal Death in Mouse
      Cortical Cultures.
AB  - beta-Amyloid peptide (Abeta) is the main component of senile plaques in patients
      with Alzheimer's disease, and is known to be a main pathogenic factor of the
      disease. Recent evidence indicates that activation of NADPH oxidase (NOX) in
      microglia or astrocytes may be a source of Abeta-induced reactive oxygen species
      (ROS). We investigated the role of neuronal NOX in Abeta-induced neuronal death
      in mouse mixed cortical cultures. Cell death was assessed by measuring lactate
      dehydrogenase efflux to bathing media 24 or 48 hr after exposure to Abeta25-35, a
      fragment of Abeta with an equivalent neurotoxic effect. Abeta25-35 induced
      neuronal death in concentration- and time- dependent manners with apoptotic
      features. Neuronal death was significantly attenuated, not only by anti-apoptotic
      drugs, such as z-VAD-fmk and cycloheximide, but also by antioxidants, such as
      trolox, ascorbic acid, and epigallocatethin gallate. We also demonstrated that
      treatment with 20 uM Abeta25-35 increased fluorescent signals in mixed cortical
      cultures, but produced only weak signals in pure astrocyte cultures in the
      presence of 2',7'-dichlorofluorescin diacetate (DCF-DA), an indicator for
      intracellular ROS. Increased DCF-DA fluorescence was markedly inhibited, not only
      by trolox, but also by selective NOX inhibitors, such as apocynin and AEBSF.
      Western blot analyses revealed that Abeta25-35 increased the expression of
      gp91phox, a main subunit of NOX in cells. The above antioxidants, apocynin, and
      AEBSF significantly attenuated neuronal death induced by Abeta25-35. Furthermore,
      the gp91phox-specific siRNA-based knockdown of NOX significantly inhibited
      neuronal death. These results suggest that activation of neuronal NOX is involved
      in Abeta25-35-induced neuronal death.

PMID- 29026708
TI  - Identification of Risk Factors Influencing In-Stent Restenosis with Acute
      Coronary Syndrome Presentation.
AB  - Although the angiographic rates of in-stent restenosis (ISR) at later months have
      reduced dramatically with the introduction of drug-eluting stents (DESs), some
      patients with ISR after implantation of DES present with acute coronary syndrome
      (ACS). Here, we sought to identify parameters influencing the likelihood of
      restenosis with ACS presentation after DES implantation. Stented patients
      (n=3,817) with DESs in the Korea University Anam Hospital percutaneous coronary
      intervention registry were reviewed retrospectively for inclusion. In this
      database, 247 age- and sex-matched patients (6.5%) with ISR were allocated to
      either the Stable ISR group (n=78) or the ACS ISR group (n=73). Predictors of in
      stent restenosis were identified with Cox regression analyses. Age (hazard ratio
      [HR], 1.14; 95% confidence interval [CI], 1.02 to 1.27; p=0.026), diabetes (HR,
      8.40; 95% CI, 1.30 to 54.1; p=0.025), use of aspirin (HR, 0.003; 95% CI, 0.0001
      to 0.63; p=0.03), clopidogrel (HR, 0.005; 95% CI, 0.001 to 0.121; p=0.001), renin
      angiotensin system (RAS) blocker (HR, 0.02; 95% CI, 0.003 to 0.14; p<0.001), use
      of first -generation DES (HR, 0.07; 95% CI, 0.009 to 0.59; p=0.014), and matrix
      metalloproteinase 2 (MMP-2) levels (HR, 1.120; 95% CI, 1.001 to 1.190; p=0.004)
      during follow-up angiograms were significant predictors of ISR with ACS
      presentation during the 3 year follow-up. Age, diabetes, the use of first
      generation DES, and increased MMP-2 levels were significant predictors of ISR
      with ACS presentation; moreover, the use of aspirin, clopidogrel, RAS blocker,
      and the use of second generation DESs prevented ISR with ACS presentation.

PMID- 29026709
TI  - Needle Aspiration Biopsy of Seminiferous Tubules (NABST) as a Diagnostic Method
      in Korea.
AB  - To evaluate the diagnostic efficacy of needle aspiration biopsy of seminiferous
      tubules (NABST) and to represent the redistributed diagnostic results
      corresponding to testicular volumes and follicle-stimulating hormone (FSH)
      levels. In this retrospective study, we investigated 65 infertile men with either
      azoospermia or oligoasthenoteratozoospermia. Following NABST, specimens were
      stained with hematoxylin and eosin and classified into five histological types.
      With pre-procedure FSH levels and testicular volumes, we evaluated the
      probabilities of detecting sperms within biopsy specimens. NABST led to the
      classification of normal spermatogenesis in 31 cases (47.7%), hypospermatogenesis
      in 23 cases (35.4%), maturation arrest in 4 cases (6.2%), and Sertoli cell only
      syndrome in 4 cases (6.2%). The success rate of reaching a histological diagnosis
      using NABST was 95.4% (62 out of 65 cases). Fourteen patients (21.5%) had a
      testicular volume <15 cc; of these, 8 patients (57.1%) had normal
      spermatogenesis, 2 patients (14.3%) had hypospermatogenesis, 2 patients (14.3%)
      had maturation arrest and 2 patients (14.3%) had Sertoli cell-only syndrome
      (SCO). Twelve patients (18.5%) had an FSH level >=10 IU; of these, 6 (50%) had
      normal spermatogenesis, 2 patients (16.7%) had maturation arrest and 4 patients
      (33.3%) had SCO. Cases with an FSH level <10 IU were positively associated with a
      probability of detecting sperm using NABST (p<0.001). NABST is a reliable tool
      for the histological diagnosis of azoospermic and oligoasthenoteratozoospermic
      patients. The diagnostic success rate was high and associated with pathological
      accuracy. NABST is a convenient procedure with few complications.

PMID- 29026710
TI  - Factors Associated with C-peptide Levels after Diagnosis in Children with Type 1
      Diabetes Mellitus.
AB  - C-peptide is the best indicator of endogenous insulin secretion in patients with
      diabetes. This study investigated the relationship between C-peptide levels and
      clinical/laboratory parameters of children with type 1 diabetes mellitus (T1DM),
      as measured at 6-month intervals after diagnosis. We retrospectively reviewed the
      data of 34 children with newly diagnosed T1DM. The study subjects were subdivided
      into a rapid progression group with C-peptide levels <0.6 ng/mL at 36 months
      (n=27; Group A) and a slow progression group with C-peptide levels >0.6 ng/mL at
      36 months (n=7; Group B). Patients in Group A had a younger mean age at diagnosis
      (A: 9+/-4.3 years vs. B: 13.6+/-3.6 years; p=0.013) and lower body mass index
      (BMI) (A: 15.5+/-2.5 kg/m2 vs. B: 18.7+/-3.3 kg/m2; p=0.035). There were fewer
      asymptomatic patients with glucosuria in Group A, with these patients showing
      more severe symptoms, such as diabetic ketoacidosis (p=0.035), than those in
      Group B. Group A also had lower initial C-peptide levels (A: 0.5+/-0.46 ng/mL vs.
      B: 1.87+/-1.08 ng/mL; p=0.001). There were no significant intergroup differences
      in sex, family history, baseline hemoglobin A1c (HbA1c), potential of hydrogen
      (pH), autoantibodies or serum insulin. Simple correlation analyses showed that C
      peptide levels were correlated with age and BMI, but not with pH, insulin, or
      HbA1c. Younger patients, who had a lower BMI, significant symptoms with
      complications, and/or a low initial C-peptide level, tended to show a rapid rate
      of decrease in C-peptide levels. Early intensive insulin therapy to preserve beta
      cell function should be considered in these groups.

PMID- 29026711
TI  - Glycated Hemoglobin and All-Cause Mortality in Korean Type 2 Diabetes.
AB  - The purpose of this study was to evaluate the association between glycated
      hemoglobin (HbA1c) and all-cause mortality in type 2 diabetes mellitus. We
      conducted a community-based prospective cohort study of 352 type 2 diabetic
      patients aged 30-92 who participated in a community diabetes complications
      screening program in Gokseng-gun, Jeollanamdo, Korea. HbA1c levels were
      categorized as <6.5%, 6.5-6.9%, 7.0-7.9%, 8.0-8.9% and >=9.0%. Patients were
      followed up on for a mean of 6.9 years. The Cox proportional hazards model was
      used to evaluate the relationship between HbA1c levels and all-cause mortality.
      During the mean follow-up period of 6.9 years, 77 patients (21.9%) died. A J
      shaped association was found between HbA1c and all-cause mortality, with the
      lowest mortality at 6.5-6.9% of HbA1c levels. Compared to patients with HbA1c of
      6.5-6.9%, patients with <6.5%, 7.0-7.9%, 8.0-8.9% and >=9.0% had an adjusted
      hazard ratio (95% confidence interval) for all-cause mortality of 1.71 (0.76
      3.84), 1.23 (0.53-2.82), 1.32(0.51-3.44) and 2.66 (1.01-7.02), respectively. We
      found a J-shaped association between glycated hemoglobin and all-cause mortality
      in Korean type 2 diabetic patients.

PMID- 29026712
TI  - Therapy-related Acute Myeloid Leukemia Following Treatment for Burkitt's
      Lymphoma.

PMID- 29026713
TI  - Vitamin C-induced Acute Kidney Injury.

PMID- 29026714
TI  - Inflammatory Pseudotumor of the Lung: A Rare Presentation with Complete
      Regression to Pharmacotherapy.

PMID- 29026715
TI  - The 'All-or-None Law' Applied to the Vertical Growth Phase of Cutaneous Malignant
      Melanoma.

PMID- 29026716
TI  - Benign Recurrent Pleomorphic Adenoma of the Parotid Gland with Perineural Space
      Invasion.

PMID- 29026717
TI  - Addition of interleukin-6 to mouse embryo culture increases blastocyst cell
      number and influences the inner cell mass to trophectoderm ratio.
AB  - OBJECTIVE: In vitro culture of preimplantation embryos is improved by grouping
      embryos together in a drop of media. Individually cultured embryos are deprived
      of paracrine factors; with this in mind, we investigated whether the addition of
      a single embryo-secreted factor, interleukin-6 (IL-6), could improve the
      development of individually cultured embryos. METHODS: Mouse embryos were
      cultured individually in 2 uL of G1/G2 media in 5% oxygen and supplemented with a
      range of doses of recombinant mouse or human IL-6. RESULTS: Mouse IL-6 increased
      hatching at doses of 0.01 and 10 ng/mL compared to the control (93% and 93% vs.
      78%, p<0.05) and increased the total number of cells at a dose of 0.1 ng/mL
      compared to the control (101.95+/-3.36 vs. 91.31+/-3.33, p<0.05). In contrast,
      the highest dose of 100 ng/mL reduced the total number of cells (79.86+/-3.29,
      p<0.05). Supplementation with human IL-6 had a different effect, with no change
      in hatching or total cell numbers, but an increase in the percentage of inner
      cell mass per embryo at doses of 0.1, 1, and 100 ng/mL compared to the control
      (22.9%+/-1.1%, 23.3%+/-1.1%, and 23.1%+/-1.1% vs. 19.5%+/-1.0%, p<0.05).
      CONCLUSION: These data show that IL-6 improved mouse embryo development when
      cultured individually in complex media; however, an excess of IL-6 may be
      detrimental. Additionally, these data indicate that there is some cross-species
      benefit of human IL-6 for mouse embryos, but possibly through a different
      mechanism than for mouse IL-6.

PMID- 29026718
TI  - The association of follicular fluid volume with human oolemma stretchability
      during intracytoplasmic sperm injection.
AB  - OBJECTIVE: Oocyte degeneration often occurs after intracytoplasmic sperm
      injection (ICSI), and the risk factor is low-quality oocytes. The follicular
      fluid (FF) provides a crucial microenvironment for oocyte development. We
      investigated the relationships between the FF volume aspirated from individual
      follicles and oocyte retrieval, oocyte maturity, oolemma stretchability,
      fertilization, and development. METHODS: This retrospective study included data
      obtained from 229 ICSI cycles. Ovarian stimulation was performed according to a
      gonadotropin-releasing hormone antagonist protocol. Each follicle was
      individually aspirated and divided into six groups according to FF volume (<1.0,
      1.0 to <2.0, 2.0 to <3.0, 3.0 to <4.0, 4.0 to <5.0, and >=5.0 mL). Oolemma
      stretchability during ICSI was evaluated using a mechanical stimulus for oolemma
      penetration, that is, the stretchability was assessed by oolemma penetration with
      aspiration (high stretchability) or without aspiration (low stretchability).
      RESULTS: Oocyte retrieval rates were significantly lower in the <1.0 mL group
      than in the >=1.0 mL groups (46.0% [86/187] vs. 67.5%-74.3% [172/255 to 124/167],
      respectively; p<0.01). Low oolemma stretchability was significantly more common
      in the <1.0 mL group than in the >=1.0 mL groups during ICSI (22.0% [13/59] vs.
      5.8%-9.4% [6/104 to 13/139], respectively; p=0.018). There was a relationship
      between FF volume and oolemma stretchability. However, there were no significant
      differences in the rates of fertilization, cleavage, >=7 cells at day 3, and
      blastocyst development among all groups. CONCLUSION: FF volume is potentially
      associated with the stretchability of metaphase II oolemma during ICSI. Regarding
      oolemma stretchability, ensuring a uniform follicular size during ovarian
      stimulation is crucial to obtain good-quality oocytes.

PMID- 29026720
TI  - Efficacy of embryo transfer on day 2 versus day 3 according to maternal age in
      patients with normal ovarian response.
AB  - OBJECTIVE: Delaying embryo transfer (ET) enables us to select among the embryos
      available for transfer and is associated with positive effects on implantation
      and pregnancy outcomes. However, the optimal day for ET of human cleavage-stage
      embryos remains controversial. METHODS: A retrospective study of 3,124 in vitro
      fertilization/intracytoplasmic sperm injection cycles (2,440 patients) was
      conducted. We compared the effects of day 2 and 3 ET on rates of implantation and
      pregnancy outcomes between young maternal age (YMA; <38 years old, n=2,295) and
      old maternal age (OMA; >=38 years old, n=829) patient groups. RESULTS: The YMA
      and OMA groups did not differ in terms of patient characteristics except for the
      proportion of unexplained factor infertility, which was significantly greater in
      the OMA group, and the proportion of arrested embryos, which was significantly
      greater in the YMA group. However, the biochemical pregnancy, clinical pregnancy,
      ongoing pregnancy, abortion, and implantation rates per cycle were not
      significantly different between day 2 and 3 ET in the YMA group or the OMA group.
      CONCLUSION: We suggest that offering patients the opportunity to decide which day
      would be suitable for ET could be part of a patient-friendly protocol that takes
      into consideration an infertile woman's circumstances and work schedule by
      allowing ET to be performed on day 2 instead of the traditional transfer on day
      3.

PMID- 29026719
TI  - ICSI significantly improved the pregnancy rate of patients with a high sperm DNA
      fragmentation index.
AB  - OBJECTIVE: Correlations between semen parameters and sperm DNA fragmentation
      index (DFI) were investigated to identify characteristics of sperm without DNA
      damage that could be used in selecting sperm for intracytoplasmic sperm injection
      (ICSI). Pregnancy outcomes were compared to determine whether in vitro
      fertilization (IVF) or ICSI is a better choice for patients who have sperm with a
      high-DFI. METHODS: Semen analysis was carried out in 388 patients who visited our
      IVF center for the first time to investigate correlations between sperm DFI and
      semen parameters. In addition, 1,102 IVF cycles in 867 patients were carried out
      in the present study; 921 cycles in the low-DFI group (DFI <30%) and 181 cycles
      in the high-DFI group (DFI >=30%). Both the low- and high-DFI groups were
      subdivided into IVF and ICSI cycle groups. RESULTS: Sperm DFI showed significant
      inverse correlations with sperm motility (r=-0.435, p<0.001) and morphology (r=
      0.153, p<0.05). Sperm DFI also showed significant correlations with rapid
      motility (r=-0.436, p<0.001), and the kinetic parameters of average-path velocity
      (r=-0.403) and linearity (r=-0.412). Although there was no significant difference
      in the pregnancy rates between IVF (48.6%) and ICSI (44.8%) in the low-DFI group,
      the pregnancy rate of ICSI cycles (44.8%, p<0.05) was significantly higher than
      IVF cycles (25.0%) in the high-DFI group. No significant difference was observed
      in the abortion rates between the low-DFI (52 of 921, 5.6%) and high-DFI groups
      (7 of 181, 3.8%). CONCLUSION: ICSI is a better choice than IVF for improving the
      pregnancy outcomes of patients who have sperm with a high DFI.

PMID- 29026721
TI  - Expression of the genes for peroxisome proliferator-activated receptor-gamma,
      cyclooxygenase-2, and proinflammatory cytokines in granulosa cells from women
      with polycystic ovary syndrome.
AB  - OBJECTIVE: To identify differences in the expression of the genes for peroxisome
      proliferator-activated receptor (PPAR)-gamma, cyclooxygenase (COX)-2, and the
      proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)
      alpha in granulosa cells (GCs) from polycystic ovary syndrome (PCOS) patients and
      controls undergoing controlled ovarian stimulation. METHODS: Nine patients with
      PCOS and six controls were enrolled in this study. On the day of oocyte
      retrieval, GCs were collected from pooled follicular fluid. Total mRNA was
      extracted from GCs. Reverse transcription was performed and gene expression
      levels were quantified by realtime quantitative polymerase chain reaction.
      RESULTS: There were no significant differences in age, body mass index, and total
      gonadotropin dose, except for the ratio of luteinizing hormone to follicle
      stimulating hormone between the PCOS and control groups. PPAR-gamma and COX-2
      mRNA was significantly downregulated in the GCs of PCOS women compared with
      controls (p=0.034 and p=0.018, respectively), but the expression of IL-6 and TNF
      alpha mRNA did not show significant differences. No significant correlation was
      detected between the expression of these mRNA sequences and clinical
      characteristics, including the number of retrieved oocytes, oocyte maturity,
      cleavage, or the good embryo rate. Positive correlations were found among the
      PPAR-gamma, COX-2, IL-6, and TNF-alpha mRNA levels. CONCLUSION: Our data may
      provide novel clues regarding ovarian GC dysfunction in PCOS, and indirectly
      provide evidence that the effect of PPAR-gamma agonists in PCOS might result from
      alterations in the ovarian follicular environment. Further studies with a larger
      sample size are required to confirm these proposals.

PMID- 29026722
TI  - MTHFR 3'-untranslated region polymorphisms contribute to recurrent pregnancy loss
      risk and alterations in peripheral natural killer cell proportions.
AB  - OBJECTIVE: To identify the associations between polymorphisms of the 3'
      untranslated region (UTR) of methylenetetrahydrofolate reductase (MTHFR) gene,
      which codes for an important regulatory enzyme primarily involved in folate
      metabolism, and idiopathic recurrent pregnancy loss (RPL) in Korean women.
      METHODS: The study population comprised 369 RPL patients and 228 controls. MTHFR
      2572C>A, 4869C>G, 5488C>T, and 6685T>C 3'-UTR polymorphisms were genotyped by
      polymerase chain reaction-restriction fragment length polymorphism analysis or by
      TaqMan allelic discrimination assays. Natural killer cell proportions were
      determined by flow cytometry. RESULTS: The MTHFR 2572-5488-6685 (A-C-T) haplotype
      had an adjusted odds ratio of 0.420 (95% confidence interval, 0.178-0.994;
      p=0.048) for RPL. Analysis of variance revealed that MTHFR 4869C>G was associated
      with altered CD56+ natural killer cell percentages (CC, 17.91%+/-8.04%; CG,
      12.67%+/-4.64%; p=0.024) and folate levels (CC, 12.01+/-7.18 mg/mL; CG, 22.15+/
      26.25 mg/mL; p=0.006). CONCLUSION: Variants in the 3'-UTR of MTHFR are potential
      biomarkers for RPL. However, these results should be validated in additional
      studies of ethnically diverse groups of patients.

PMID- 29026723
TI  - Circadian Rhythm Disruption and Subsequent Neurological Disorders in Night-Shift
      Workers.
AB  - A large number of people in highly industrialized society are employed in night
      shift work. Night-shift work interrupts the 24-hour daily cycle known as the
      circadian rhythm, as well as melatonin synthesis. These disruptions can make the
      body susceptible to oxidative stress and neural damage. In this regard, it is
      recommended that employees avoid long-term exposure to night-shift work.

PMID- 29026724
TI  - Lifestyle Intervention for Obese Women.
AB  - Obesity produces various physical and psychological health risks in women,
      including effects on reproductive health. In particular, the possibility of
      infertility in obese women is high. Lifestyle interventions involving nutrition
      education, physical activity, and stress management have been shown to be
      effective in improving the health of obese subjects. Therefore, it is necessary
      to develop and apply a lifestyle intervention program to promote reproductive
      health in obese women.

PMID- 29026725
TI  - Effects of Exercise Training on Physical Fitness and Biomarker Levels in Breast
      Cancer Survivors.
AB  - BACKGROUND: Exercise has been identified as a beneficial intervention to enhance
      quality of life in breast cancer survivors. In addition, there has been a
      noteworthy increase in studies emphasizing the benefits of exercise in cancer. We
      sought to summarize the empirical literature concerning the effects of exercise
      on physical fitness and biomarker levels in breast cancer survivors according to
      the type of exercise. METHODS: We searched PubMed and PubMed Central for studies
      on the association of exercise with the levels of various biomarkers and physical
      fitness in breast cancer survivors. We investigated the effects of different
      types of exercise (aerobic, resistance, or combined) on breast cancer survivors,
      with changes in physical fitness and biomarker levels as the primary outcomes.
      RESULTS: In total, 118 research papers published from 2012 to July 2016 were
      retrieved from PubMed and PubMed Central. Of these, 24 papers met our inclusion
      criteria. All types of exercise were found to improve physical fitness in breast
      cancer survivors. However, the results with regard to biomarkers were
      controversial. CONCLUSION: The findings of this review suggest that combined
      exercise is associated with better outcomes than aerobic or resistance exercise
      alone in breast cancer survivors.

PMID- 29026726
TI  - Hand Grip Strength and Gender: Allometric Normalization in Older Adults and
      Implications for the NIOSH Lifting Equation.
AB  - BACKGROUND: Many countries are experiencing an aging workforce with women workers
      making up a growing proportion. Workplaces often require employees to complete
      lifting tasks that require the ability of the hand to grasp an implement
      (coupling). The National Institute for Occupational Safety and Health (NIOSH) has
      developed an equation for manual lifting tasks hoping to minimize the potential
      for a workplace back-injury related to a lifting task. The NIOSH lifting equation
      relies upon stress variables including a coupling factor. However, little is
      known regarding grip strength as related to the NIOSH lifting equation coupling
      factor. The purpose of this study was to investigate differences in grip strength
      due to gender in older adults. METHODS: The participant's (68-88 years) maximal
      grip (MG) strength measures were collected for each hand with a hand grip
      dynamometer (kg). MG scores were converted to Newtons (N), normalized to body
      mass, and allometrically scaled. Measures of MG were than compared between
      genders with an independent t-test. RESULTS: The hand grip measures of MG (kg)
      [male: 30.3 +/- 5.6, female: 10.6 +/- 3.3], MG (kg) / body mass (kg) [male: 0.35
      +/- 0.06, female: 0.16 +/- 0.04], MG (N) / (body mass (kg))0.67 [male: 15.1 +/-
      2.5, female: 6.2 +/- 1.7], and MG (N) / (body height (m))1.84 [male: 103.6 +/-
      18.6, female: 42.6 +/- 10.6] were all significantly lower (p < 0.0001) for women
      than men. Regardless of how grip strength was reported, there is a strong
      difference in grip strength between genders in this sample. The NIOSH lifting
      equation does not account for varying grip strength due to aging and gender
      differences. CONCLUSIONS: It is recommended that grip strength variability be
      accounted for in the coupling factor of the NIOSH lifting equation.

PMID- 29026727
TI  - Adverse Effects of Prolonged Sitting Behavior on the General Health of Office
      Workers.
AB  - BACKGROUND: Excessive sitting behavior is a risk factor for many adverse health
      outcomes. This study aimed to survey the prevalence of sitting behavior and its
      adverse effects among Iranian office workers. METHODS: This cross-sectional study
      included 447 Iranian office workers. A two-part questionnaire was used as the
      data collection tool. The first part surveyed the demographic characteristics and
      general health of the respondents, while the second part contained the Nordic
      Musculoskeletal Questionnaire (NMQ) to assess symptoms. Statistical analyses were
      performed using the Statistical Package for the Social Sciences software using
      Mann-Whitney U and Chi-square tests and multiple logistic regression analysis.
      RESULTS: The respondents spent an average of 6.29 hours of an 8-hour working
      shift in a sitting position. The results showed that 48.8% of the participants
      did not feel comfortable with their workstations and 73.6% felt exhausted during
      the workday. Additionally, 6.3% suffered from hypertension, and 11.2% of them
      reported hyperlipidemia. The results of the NMQ showed that neck (53.5%), lower
      back (53.2%) and shoulder (51.6%) symptoms were the most prevalent problem among
      office workers. Based upon a multiple logistic regression, only sex had a
      significant association with prolonged sitting behavior (odds ratio = 3.084). Our
      results indicated that long sitting times were associated with exhaustion during
      the working day, decreased job satisfaction, hypertension, and musculoskeletal
      disorder symptoms in the shoulders, lower back, thighs, and knees of office
      workers. CONCLUSION: Sitting behavior had adverse effects on office workers.
      Active workstations are therefore recommended to improve working conditions.

PMID- 29026728
TI  - Analysis of the Relationship between Sleep Duration and Body Mass Index in a
      South Korean Adult Population: A Propensity Score Matching Approach.
AB  - BACKGROUND: One-third of the present adults in South Korea are obese, and
      previous studies have demonstrated that sleep duration is considered a risk
      factor for obesity. Hence, I assessed the relationship between sleep duration and
      body mass index in a South Korean adult population. METHODS: This cross-sectional
      study consists of a representative sample of 4,218 South Korean adults (20-64
      years) who participated in the sixth Korea National Health and Nutrition
      Examination Survey (2015). As statistical analysis methods, data were analyzed
      using chi-square test and multiple logistic regression. Propensity score matching
      (PSM) was applied to control selection bias, and obesity-related factors were
      used as covariates in PSM. RESULTS: According to the multiple logistic regression
      analysis, people who sleep for more than seven hours a day were less likely to be
      obese than those who sleep for less than seven hours a day in the pre-match (OR =
      0.75, 95%CI = 0.65-0.88) and post-match (OR = 0.77, 95%CI = 0.65-0.90) samples.
      CONCLUSIONS: This finding suggests that South Korean adults who reported sleeping
      more than 7 hours a day were linked to decreased body mass index. Hence, the
      proper amount of sleep is necessary to reduce the prevalence of obesity in this
      population.

PMID- 29026729
TI  - Probiotics in Children: What Is the Evidence?
AB  - The number of papers discussing probiotics increases tremendously that limits the
      possibility for primary care physicians and clinicians to stay updated.
      Therefore, the aim of this paper will be to summarize available evidence of
      probiotic use in well-defined clinical indications of importance for
      pediatricians. Based on currently available evidence certain probiotic strains
      (Lactobacillus rhamnosus GG [LGG] and Saccharomyces boulardii) have proven effect
      in the treatment of acute gastroenteritis and prevention of antibiotic associated
      diarrhea. Furthermore, LGG was proven to be effective in prevention of nosocomial
      diarrhea and respiratory tract infection in day care centers. In conclusion, not
      all probiotic strains have same efficacy for all clinical indications, therefore,
      only strains with proven efficacy and safety should be recommended.

PMID- 29026730
TI  - Important Role of Medical Training Curriculum to Promote the Rate of Human Milk
      Feeding.
AB  - The rate of human milk feeding has been decreasing despite the diverse efforts of
      many physicians and nurses, as well as numerous professional organizations and
      various international health institutions. The number of physicians and nurses
      who can provide proper guidance for human milk feeding and offer appropriate
      knowledge and techniques to allow the most beneficial and convenient manner of
      breastfeeding is quite deficient. It is suggested that physicians and nurses be
      trained to teach and educate about the medical importance of human milk feeding
      to lactating mothers. This can be accomplished through systemic changes in
      medical education and clinical practice. However, the curricula of medical
      schools in Korea do not provide enough education and training to effect an
      increase in human milk feeding. The author strongly recommends that the
      educational objectives for medical schools and resident training offer more
      education and training concerning so that they are well aware of breastfeeding
      basics and techniques, and have ability to solve lactation-associated clinical
      problems.

PMID- 29026731
TI  - Not All Children with Cystic Fibrosis Have Abnormal Esophageal Neutralization
      during Chemical Clearance of Acid Reflux.
AB  - PURPOSE: Acid neutralization during chemical clearance is significantly prolonged
      in children with cystic fibrosis, compared to symptomatic children without cystic
      fibrosis. The absence of available reference values impeded identification of
      abnormal findings within individual patients with and without cystic fibrosis.
      The present study aimed to test the hypothesis that significantly more children
      with cystic fibrosis have acid neutralization durations during chemical clearance
      that fall outside the physiological range. METHODS: Published reference value for
      acid neutralization duration during chemical clearance (determined using combined
      impedance/pH monitoring) was used to assess esophageal acid neutralization
      efficiency during chemical clearance in 16 children with cystic fibrosis (3 to
      <18 years) and 16 age-matched children without cystic fibrosis. RESULTS: Duration
      of acid neutralization during chemical clearance exceeded the upper end of the
      physiological range in 9 of 16 (56.3%) children with and in 3 of 16 (18.8%)
      children without cystic fibrosis (p=0.0412). The likelihood ratio for duration
      indicated that children with cystic fibrosis are 2.1-times more likely to have
      abnormal acid neutralization during chemical clearance, and children with
      abnormal acid neutralization during chemical clearance are 1.5-times more likely
      to have cystic fibrosis. CONCLUSION: Significantly more (but not all) children
      with cystic fibrosis have abnormally prolonged esophageal clearance of acid.
      Children with cystic fibrosis are more likely to have abnormal acid
      neutralization during chemical clearance. Additional studies involving larger
      sample sizes are needed to address the importance of genotype, esophageal
      motility, composition and volume of saliva, and gastric acidity on acid
      neutralization efficiency in cystic fibrosis children.

PMID- 29026732
TI  - Prevalence and Epidemiological Characteristics of Endoscopically Proven Reflux
      Esophagitis in Children in Korea.
AB  - PURPOSE: The prevalence of reflux esophagitis (RE) has increased recently in
      Korea. Little is known concerning the prevalence and characteristics of RE in
      pediatric patients. This study investigated the prevalence and influence of risk
      factors in endoscopically proven RE in Korea in pediatric patients over a period
      of 14 years. METHODS: A retrospective chart review of all patients between the
      ages of 1 month and 20 years who underwent esophagogastroduodenoscopy at Samsung
      Medical Center between 2001 and 2014 was carried out. Univariate and multivariate
      analyses were conducted to identify independent risk factors for RE. RESULTS: The
      prevalence rate of endoscopically proven RE in this study was 28.7% (978/3,413).
      The prevalence of RE increased from 11.8% from 2001 to 2007 to 37.7% from 2008 to
      2014. Multivariate logistic regression analysis revealed that residency in the
      Greater Gangnam area (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.02
      1.44) and age (OR, 1.13; 95% CI, 1.11-1.15) were significant predictive factors
      for the presence of RE. CONCLUSION: The prevalence rate of endoscopically proven
      pediatric RE has increased over the past 14 years. Residency and older age are
      more important independent risk factors for pediatric RE in Korea.

PMID- 29026733
TI  - Safety of a New Synbiotic Starter Formula.
AB  - PURPOSE: Breastfeeding is the best way to feed all infants, but not all infants
      can be (exclusively) breastfed. Cow's milk based infant formula is the second
      choice infant feeding. METHODS: The safety of a new synbiotic infant formula,
      supplemented with Bifidobacterium lactis and fructo-oligosaccharides, with
      lactose and a whey/casein 60/40 protein ratio was tested in 280 infants during 3
      months. RESULTS: The median age of the infants at inclusion was 0.89 months.
      Weight evolution was in accordance with the World Health Organization growth
      charts for exclusive breastfed infants. The evolution of all anthropometric
      parameters (weight-for-length z score and body mass index-for-age z score) was
      within the normal range. The incidence of functional constipation (3.2%), daily
      regurgitation (10.9%), infantile crying and colic (10.5%) were all significantly
      lower than the reported median prevalence for a similar age according to
      literature (median value of 7.8% for functional constipation, 26.7% for
      regurgitation, 17.7% for infantile colic). CONCLUSION: The new synbiotic infant
      starter formula was safe, resulted in normal growth and was well tolerated.
      Functional gastro-intestinal manifestations (functional constipation,
      regurgitation and colic) were significantly lower than reported in literature.
      Synbiotics (Bifidobacterium lactis and fructo-oligosaccharides) in cow's milk
      based infant formula bring the second choice infant feeding, formula, closer to
      the golden standard, exclusive breastfeeding.

PMID- 29026734
TI  - Cytomegalovirus Infection under a Hybrid Strategy in Pediatric Liver
      Transplantation: A Single-Center Experience.
AB  - PURPOSE: To evaluate the outcomes of a hybrid prophylactic strategy to prevent
      cytomegalovirus (CMV) disease in pediatric liver transplantation (LT) patients.
      METHODS: CMV DNAemia was regularly monitored by quantitative nucleic acid
      amplification test (QNAT) and was quantified in all children. CMV infection and
      disease were defined according to the International Consensus Guidelines. The
      hybrid strategy against CMV infection consisted of universal 3-week prophylaxis
      and preemptive treatment of intravenous ganciclovir regardless of the recipient's
      serostatus. RESULTS: A total of 143 children who underwent living donor LT were
      managed using the hybrid strategy. The overall incidence of CMV infection by QNAT
      was 48.3% (n=69/143). The highest CMV DNAemia positivity was observed in 49.2%
      (n=60/122) of children in the D+/R+ group, followed by 46.7% (n=7/15) in the D+/R
      group. CMV disease was noted in 26.1% (n=18/69) patients. Forty-three (62.3%)
      children had undergone preemptive therapy consisting of intravenous ganciclovir.
      No symptomatic patients developed tissue-invasive disease, resulting in no CMV
      associated mortality. CONCLUSION: The incidence of CMV infection was high in
      pediatric LT patients despite the hybrid strategy. However, tissue-invasive
      disease in pediatric LT did not occur.

PMID- 29026735
TI  - The Association between Socioeconomic Status and Obesity in Korean Children: An
      Analysis of the Fifth Korea National Health and Nutrition Examination Survey
      (2010-2012).
AB  - PURPOSE: Obesity is one of the most common health problems among children and its
      prevalence has increased in recent decades. Socioeconomic status (SES) is a well
      known risk factor for childhood obesity although the associations were different
      across countries. Previous studies in other countries have reported a positive
      association between childhood obesity and SES in developing countries, and
      inverse correlation has been reported in developed countries. For this reason, we
      wanted to investigate the relationship between SES and obesity in Korean
      children. METHODS: Data were acquired 3,095 boys and girls who participated in
      the fifth Korea National Health and Nutrition Examination Survey, which was
      conducted from 2010 to 2012. Body mass index was calculated from measured
      anthropometric data using the 2007 Korean National Growth Charts. RESULTS: Upon
      univariate analysis, we did not find any statistically significant differences in
      the parental employment status, monthly family income between children with and
      without obesity. Multiple logistic regression analysis showed childhood obesity
      was positively associated with maternal overweight (OR, 1.889; 95% CI, 1.079
      3.309), maternal obesity (OR, 3.409; 95% CI, 2.228-5.215) and paternal obesity
      (OR, 2.135; 95% CI, 1.257-3.627). CONCLUSION: The present study showed that
      socioeconomic status might not an important risk factor for obesity in Korean
      children. These results warrant further studies to clarify the association
      between SES and obesity in Korean children.

PMID- 29026736
TI  - Giant Duplication Cyst Presenting as a Discharging Umbilicus.
AB  - Alimentary tract duplication cysts are rare congenital anomalies, most commonly
      located in the ileum, but may present anywhere from mouth to anus.Clinically,
      they may be asymptomatic, incidentally diagnosed or may present with obstruction,
      volvulus, intussusception or gastrointestinal bleed. Here we report a case of a
      one year old male child presenting in gasping state and shock. Despite the
      initial strong suspicion of Meckel's diverticulum and tubercular abdomen, the
      final diagnosis remained elusive till exploratory laparotomy was performed which
      revealed a duplication cyst of ileum with perforation into the umbilicus.
      Duplication cyst should always be kept as a differential diagnosis so that early
      intervention can help in better management.

PMID- 29026737
TI  - Eosinophilic Gastrointestinal Disorder Presenting as Intractable Vomiting and
      Ascites in a Young Girl.
AB  - Eosinophilic gastrointestinal disorder (EGID) is a rare disease in children that
      affects the bowel wall, with eosinophilic infiltration in the absence of any
      other causes for eosinophilia. The etiology remains unknown, but allergies and
      immunological imbalance are suspected triggers. We encountered a case of serosal
      EGID presenting as intractable vomiting and ascites in a 9-year-old girl, after
      influenza virus infection. Peripheral eosinophilia was not present. The diagnosis
      was confirmed by biopsy of the bowel wall through laparotomy and endoscopy, and
      controlled by 2 courses of steroid therapy due to recurring symptoms. Influenza
      virus infection was assumed to play a role in the onset of EGID through a Th2
      response that stimulated eosinophilic infiltration in the GI tract. We therefore
      report this case along with a literature review.

PMID- 29026738
TI  - Two Cases of Colonoscopic Retrieval of a Foreign Body in Children: A Button
      Battery and an Open Safety Pin.
AB  - Ingestion of foreign body in children is a relatively common problem among
      paediatric population. The foreign bodies mostly pass spontaneously through the
      gastrointestinal tract. However, complications can occur according to its
      anatomical location, the characteristics of the foreign body, and delays in
      management. Although the cases of ingested button batteries or sharp objects
      impacted at the gastrointestinal tract can be very serious, there have been very
      only a few cases have reported colonoscopic removal of these dangerous foreign
      bodies in adults, and there have been no case reports in children. We report one
      case of a button battery and one case of an open safety pin, both impacted in the
      terminal ileum that had moved from the stomach within a few hours of ingestion
      and were eventually managed by colonoscopy without any complications.

PMID- 29026739
TI  - Mohalla Clinics of Delhi, India: Could these become platform to strengthen
      primary healthcare?
AB  - The mohalla or community clinics in Delhi, India aims to provide basic health
      services to underserved population in urban settings. This article reviews and
      analyzes the strengths & limitations of the concept and explores the role these
      clinics can play in (1) reforming urban health service delivery, (2) addressing
      health inequities, and (3) strengthening primary health care. These clinics
      provide basic healthcare services to people, in underserved areas, in a
      responsive manner, have brought health higher on the political agenda and the
      governments of a number of Indian states have shown interest in adoption (of a
      variant) of this concept. Strengths notwithstanding, the limitations of these
      clinics are: curative or personal health services focus and relatively less
      attention on public/population health services. It is proposed that while setting
      up these clinics, the government should built upon existing health system
      infrastructure such as dispensaries, addressing the existing challenges. The new
      initiative need not to be standalone infrastructure, rather should aimed at
      health system strengthening. These need to have a functional linkage with
      existing programs, such as Urban Primary Health Centres (U-PHCs) under national
      urban health mission (NUHM) and could be supplemented with overall efforts for
      innovations and other related reforms. The author proposes a checklist 'Score
      100' or 'S-100', which can be used to assess the readiness and preparedness for
      such initiative, should other state governments and/or major city in India or
      other countries, plan to adopt and implement similar concept in their settings.
      In last 18 months, the key contribution of these clinics has been to bring health
      to public and political discourse. Author, following the experience in Delhi,
      envisions that these clinics have set the background to bring cleanliness-health
      education-sanitation-social sectors (C-H-E-S-S or CHESS) as an alternative to
      Bijli-Sadak-Paani (B-S-P) as electoral agenda and political discourse in India.
      The article concludes that Mohalla Clinics, could prove an important trigger to
      initiate health reforms and to accelerate progress towards universal health
      coverage in India.

PMID- 29026741
TI  - Salt reduction strategy at population level.
AB  - World is facing a huge burden of noncommunicable diseases such as hypertension,
      ischemic health diseases, and stroke. Moreover, the developing countries have had
      a relatively speedy rise of the problem, with noncommunicable diseases occurring
      at much lower age as compared to the developed world. The World Health
      Organization, therefore, recommends reduction in salt intake at population level
      to <5 g/day. Not all researchers and public health physicians agree to it,
      leading to conflicting information for a primary care physician. This evidence
      based summary documents this polarization of the recommendations regarding salt
      reduction and acknowledges the ongoing challenge primary care physicians face
      when following such evidence based guidelines.

PMID- 29026740
TI  - Diabetes and Ramadan: A concise and practical update.
AB  - Despite the fact that the month of Ramadan includes 29-30 days and the duration
      of fasting for each day can last for between 12 and 16 h, it was estimated that a
      large number of individuals with diabetes do fast during Ramadan. In light of
      recent advancement of new pharmacological agents, drugs such as vildagliptin,
      sitagliptin, and liraglutide were found to be safe to use during this month of
      fasting. These therapeutic agents can also be used in combination with metformin.
      The use of sulfonylureas, in most of the recent guidelines about diabetes and
      Ramadan, seems not to gain much support due to the risk of hypoglycemia. In this
      review, we also addressed the use of insulin injection, insulin pump, and
      education before, during, and after Ramadan. Further research is needed to
      determine (i) the therapeutic benefit of new antidiabetic agents and (ii) the
      benefit of new technologies for the treatment of diabetes.

PMID- 29026742
TI  - Contraceptive behavior of couples undergoing sterilization in an Eastern State of
      India.
AB  - BACKGROUND: As a part of a larger study for evaluating the effectiveness of a
      community-based family welfare program, this study assessed the contraceptive
      behavior of couples preceding sterilization and termination of pregnancies, if
      any during the interim period. METHODS: During May-June 2013, a cross-sectional
      study was undertaken in three districts of Odisha, an eastern state of India with
      poor maternal health indicators. Using a 15 * 14 cluster design with probability
      proportionate to size sampling 15 village clusters from each district were
      selected. Seven beneficiaries from the catchment area of two Accredited Social
      Health Activist of the selected villages were interviewed (14 respondents from
      each village) using a pretested predesigned questionnaire. RESULTS: A total of
      630 clients with either of the partner having undergone sterilization were
      interviewed. Male partner having undergone vasectomy was < 1% (n = 3). The mean
      age (standard error mean [SEM]) of the respondent women was 34.54 +/- 0.26 years.
      The mean age of the women at the time of sterilization was 27.12 (standard
      deviation [SD], 3.8, SEM 0.15 and median 26.83 years) years. Women as young as 22
      years had undergone sterilization. Average family size was 2.81 with about 29
      respondents (4.5%) having 5 or more children. The average duration between the
      last childbirth (LCB) to the date of sterilization was 18.37 months (range: 1-142
      months, SD: 24 months, SE: 10 months). Seventy-two percent of the respondents did
      not use any method of contraception during this period. Methods adopted for
      contraception among the users was pill (20%) followed by condom (7%), and
      intrauterine contraceptive device (IUCD) was least used (0.2%). Ten percent of
      the women had undergone abortion before sterilization either once (7.9%) or more
      than once (2.1%). CONCLUSION: There was a gross delay in sterilization after LCB.
      Postpartum sterilization or IUCD were also not used frequently.

PMID- 29026743
TI  - Management of diabetic ketosis and ketoacidosis with intramuscular regular
      insulin in a low-resource family medicine setting.
AB  - BACKGROUND: India is facing an epidemic of diabetes mellitus (DM). Effective
      management of complications of DM is a challenge in resource-poor areas of India.
      This study addresses the need to explore low-cost methods to manage diabetic
      ketosis (DK) and diabetic ketoacidosis (DKA). OBJECTIVES: To demonstrate the use
      of intramuscular (IM) regular insulin as a safe alternative method to control DK
      and DKA in a family practice setting. MATERIALS AND METHODS: A retrospective
      chart review was done for 34 patients admitted with DK and DKA in a family
      medicine unit for the urban poor over 5 years. Data on age, sex, precipitating
      factors, blood pressure, number of days of hospitalization, amount of insulin,
      and time required to control blood glucose (BG) and to correct acidosis were
      entered into EpiData version 3.1 and analyzed using SPSS software version 17.
      RESULTS: Administration of IM regular insulin was effective in reducing the BG to
      < 250 mg/dL in patients with DK and DKA. The mean time required for this in the
      ketosis group was 3.8 h and in the ketoacidosis group was 3.9 h. The mean amount
      of insulin required for correction of acidosis in the ketoacidosis group was 72.3
      units and the mean time to achieve this was 33 h. Of the 34 patients, only one in
      the ketoacidosis group had hypoglycemia. There was no fatality or referral of any
      patient. CONCLUSION: This study demonstrates that IM regular insulin is a safe
      alternative method in managing DK and DKA in a family medicine setting.

PMID- 29026744
TI  - Profile of drug-resistant tuberculosis in Western Maharashtra.
AB  - CONTEXT: Drug-resistant tuberculosis (TB) strains have evolved mainly due to
      incomplete or improper treatment of TB patients and are one of the hurdles in
      controlling TB problem. It is better to understand the magnitude and
      comorbidities associated with drug-resistant TB. AIM AND OBJECTIVES: (1) To study
      some of the sociodemographic profile and history of TB treatment of drug
      resistant TB cases. (2) To study their drug-resistance pattern and their
      comorbidity profile. SETTINGS AND DESIGN: It was a record-based study
      descriptive, cross-sectional study of drug-resistant TB cases that were referred
      to State TB Training and Demonstration Centre (STDC). MATERIALS AND METHODS: The
      data were collected by means of use of TB patient treatment register of those
      tested at STDC during first two quarters of the year 2012 (from January to June
      2012). Sputum samples of all the cases were subjected to concentrated microscopy,
      and all positive samples were tested by GeneXpert and Line Probe Assay for drug
      susceptibility testing (DST) for isoniazid and rifampicin. STATISTICAL ANALYSIS:
      The findings were analyzed with Epi info7, using the mean, standard deviation,
      Chi-square test. RESULTS: The mean age of the patients was 35.65 +/- 13.59 years,
      majority 71.87% were males. The majority of patients 72.91% had the previous
      history of TB. A majority 68.75% of the patients had acquired drug resistance,
      and 73.95% of cases were suffering from multidrug-resistant TB. A total of 28.13%
      patients had self-reported comorbidity. A majority 62.5% had failure as the
      treatment outcome for the current episode of TB and mortality was seen in 12.5%
      cases. CONCLUSIONS: Majority had failure as a treatment outcome due to advanced
      disease status or late diagnosis. Rapid diagnosis and DST for first- and second
      line drugs will greatly improve the clinical outcome.

PMID- 29026745
TI  - Psychometric properties of the Trust in Physician Scale in Tamil Nadu, India.
AB  - CONTEXT: Trust in health care is of high intrinsic value. It also leads to
      positive outcomes such as better treatment adherence and disclosure of sensitive
      information. Therefore, there is a need to measure trust in health care
      objectively. AIMS: To assess the psychometric properties of the Trust in
      Physician Scale in Tamil Nadu, India. SETTINGS AND DESIGN: The study was
      conducted in a private tertiary hospital setting in Tamil Nadu by a cross
      sectional survey design. METHODS: The Trust in Physician Scale and General Trust
      Scale were administered to 288 participants in the waiting area of a tertiary
      care hospital in Tamil Nadu. STATISTICAL ANALYSIS: Descriptive statistics,
      exploratory factor analysis, and Cronbach's alpha statistics were used to assess
      the validity and reliability of the scale. RESULTS: The respondents were
      predominantly men from rural areas, older than 35 years of age, and with lesser
      than 8 years of schooling. The questionnaire had acceptable internal consistency
      with Cronbach's alpha of 0.707 (95% confidence interval 0.654-0.755). Exploratory
      factor analysis divided the questionnaire into four domains. Seven items loaded
      into factor 1 which explained dependability and competence of the physician, two
      items loaded on factor 2, and one each in factors 3 and 4. The latter four items
      had very low item to total correlations and hence did not contribute much to the
      questionnaire. CONCLUSIONS: The Trust in Physician questionnaire needs to be
      modified to accurately measure the domains of trust in the context of the study
      area. More qualitative studies are required to understand the domains of trust in
      this cultural and social context.

PMID- 29026746
TI  - Effectiveness of first-aid training on school students in Singur Block of Hooghly
      District, West Bengal.
AB  - OBJECTIVE: First aid is the helping behavior and initial care provided for an
      acute illness or injury. Students have the potential for changing the health
      scenario of the society if properly groomed and educated. The objective of the
      study is to evaluate the effectiveness of educational intervention on the first
      aid among middle school students of a rural school in West Bengal. MATERIALS AND
      METHODS: A total of 230, 6th and 7th standard students were given a self
      administered questionnaire for assessing their baseline knowledge about
      management of common injuries followed by educational intervention with a
      systematically devised teaching module during February to March 2016. Post
      intervention evaluation of their knowledge acquisition was done after 2 weeks
      with same questionnaire. RESULTS: The baseline knowledge on the management of
      selected injuries was found to be insufficient among the study subjects. Paired t
      test was performed to compare the pre- and post-test scores of knowledge and
      attitude of the students about first aid, and there was a significant change in
      knowledge from pretest score (mean = 1.50, standard deviation [SD] =0.47) to
      posttest score (mean = 6.53, SD = 1.30). To quantify the effectiveness of health
      education, effect size (Cohen's d) was derived. For knowledge score, Cohen's d
      was 5.14 with large effect size indicating highly effective impact of the
      training program. Significant change was also noticed regarding attitude
      regarding first aid as evident from increase in pretest score (mean = 1.19, SD =
      0.96) to posttest score (mean = 3.17, SD = 1.03); Cohen's d was 1.88 with medium
      effect size. CONCLUSION: Inculcating first-aid training in the school curriculum
      can be a fruitful investment in ensuring proper and timely management of
      illnesses and injuries not only for the school children but also for the
      community at large.

PMID- 29026747
TI  - Acanthosis nigricans: A screening test for insulin resistance - An important risk
      factor for diabetes mellitus type-2.
AB  - BACKGROUND: Acanthosis nigricans (AN) is one of the signs suggestive of high
      insulin resistance (IR). IR is one of the mechanisms involved in pathogenesis of
      diabetes mellitus type-2 (DM Type-2). Thus, early detection of IR in children may
      allow us time to intervene well before the development of DM Type-2. In this
      study, 62% of children having AN had high IR. In children having both, AN and
      high body mass index (BMI), the incidence of IR was about 80%. This suggests that
      these easily detectable parameters alone can be useful in screening children at
      high risk of developing DM Type-2 in future. These simple criteria thus hold
      promise for use in high throughput screening programs for diabetes. CONTEXT: A
      pilot study conducted by the authors showed that children with AN have a high
      incidence of IR. The detection of IR in children may allow us time to intervene
      well before the development of DM Type-2. Detection of DM Type-2 by hyperglycemia
      may be too late to prevent the onset of microvascular changes. AIMS: This study
      aims to determine whether easily observable presence of AN can be used to screen
      for increased IR in children, and thereby to detect this important risk factor
      for DM Type-2. SETTINGS AND DESIGN: Cross-sectional, observational study. Two
      schools, one with children belonging to average economic background and the
      other, a residential school with children of affluent parents. Selection of
      children was done randomly. SUBJECTS AND METHODS: The study was conducted among
      507 children in the age group of 10-18 years. Physical examination for the
      detection of AN, height and weight measurements, waist circumference, fasting
      plasma glucose, fasting plasma insulin, and lipid profile was done. Homeostatic
      model assessment of insulin resistance was calculated. STATISTICAL ANALYSIS USED:
      Data analysis was performed using descriptive statistics and inferential
      statistical methods. The association between categorical variables was done by
      Chi-square test. RESULTS: The presence of AN positively correlated with high IR,
      and when combined with increased BMI, the incidence rate of IR is 80%.
      CONCLUSIONS: AN can be used as a screening method to identify children at risk of
      DM Type-2-since those who have high IR have a high possibility of having DM Type
      2 in future. Hence, early screening and simple, but effective interventional
      strategies can be instituted at this age, which may prevent or delay diabetes in
      the long run.

PMID- 29026748
TI  - Knowledge and awareness regarding menstruation and HIV/AIDS among schoolgoing
      adolescent girls.
AB  - INTRODUCTION: Menstruation in our country is associated with various myths and
      restrictions leading to lack of awareness among adolescent girls. Insufficient
      menstrual hygiene practices are the cause of stress associated with menstruation
      and reproductive tract infections. Sexually transmitted infections and HIV/AIDS
      are not openly discussed in our society making adolescents vulnerable to them.
      AIM: To assess the knowledge of school going adolescent girls regarding menstrual
      hygiene and HIV/AIDS. MATERIALS AND METHODS: Girls studying in class 8th-12th
      standard and who have attained menarche were included in the study. A predesigned
      questionnaire, which consisted of questions related to menstrual awareness and
      knowledge about HIV/AIDS was used for data collection. Data was analysed using
      SPSS software and results were interpreted into percentages. RESULTS: 282 girls
      took part in the study. Mean age of girls was 14.70 +/- 1.5 years. Median age of
      girls was 15 years. Knowledge regarding menstrual hygiene and HIV/AIDS was found
      to be only satisfactory leaving a scope of improvement. Mother was the main
      source of information regarding both menstruation and HIV/AIDS. CONCLUSION: A
      comprehensive health education programme involving mothers is required to remove
      various misconceptions and taboos associated with menstruation and make it a
      pleasant experience for adolescent girls. Information, education and awareness
      programmes need to be strengthened to spread awareness regarding HIV/AIDS.

PMID- 29026750
TI  - Visual impairment among 10-14-year school children in Puducherry: A cross
      sectional study.
AB  - INTRODUCTION: According to the 2010 estimates by the World Health Organization,
      nearly 285 million (4.24% of total population) people of all ages worldwide are
      visually impaired. Almost 18.9 million children under 15 years of age are
      visually impaired globally. In developing countries, 7%-31% of childhood
      blindness and visual impairment is avoidable. MATERIALS AND METHODS: The study
      was conducted as a cross-sectional study among 1884 school students in
      Puducherry, in the age group of 10-14 years. A child with presenting maximum
      vision <=6/12 Snellen equivalent in the better eye is considered visually
      impaired. Data were entered in Microsoft Excel 2013 and analyzed using the
      statistical software SPSS version 21.0. Chi-square test was applied for testing
      difference in proportion and a P < 0.05 was considered statistically significant.
      RESULTS: The overall prevalence of visual impairment (vision <=6/12) among the
      study participants was 6.37% (95% confidence interval = 5.27-7.47). The
      prevalence of visual impairment increased with age and it was found to be high
      among male students (6.6%) when compared to female students (6%). Presenting
      vision of 6/6 was observed in 79.8% of the children while with pinhole
      correction, the proportion increased to 94.6%. CONCLUSION: The prevalence of
      visual impairment in our study population was found to be 6.37% and the
      prevalence was even higher among children who belonged to schools of urban region
      or private schools. Children with a positive family history of spectacle use were
      more likely to have visual impairment.

PMID- 29026749
TI  - Implementation of a Schedule II patient agreement for opioids and stimulants in
      an adult primary care practice.
AB  - BACKGROUND: The consumption of controlled substances in North Carolina and the
      nation has created a health crisis with epidemic levels of medication diversion,
      abuse, overdose and death. Primary care providers are the principal prescribers
      of controlled substances and at greatest risk of encountering patients that abuse
      medications. Guidelines recommend patient agreements with monitoring requirements
      when prescribing opioids and stimulants. Studies have focused on opioids and
      excluded stimulants. Adherence to recommended monitoring requirements has not
      been fully evaluated. METHODOLOGY: This was a quality improvement project using
      the Plan-Do-Check-Act procedure. The following outcome measures were evaluated:
      signed agreement on file, prescription monitoring program (pmp) checks, urine
      screens, and prescriptions written without a mandatory visit. IMPLEMENTATION:
      Who: patients aged 19 and over prescribed a long-term Schedule II medication for
      the chronic conditions of pain and/or attention deficit hyperactivity disorder.
      What: implemented a patient agreement and measured fidelity to components of the
      agreement. When: seven months pre- to seven months post-implementation. Where: in
      an adult primary care practice with approximately 2,500 patients. How: an
      agreement was implemented with monthly feedback provided. RESULTS: Post
      implementation, 94% of patients meeting criteria had a signed agreement in their
      medical record. Adherence to urine screening improved from 5.3% to 71.1%.
      Guideline adherence to pmp checks improved from 11.3% to 99.0%. Guideline
      deviation for prescriptions written without a visit improved from 20.6% to 0%.
      All improvements were statistically significant (P < .001). CONCLUSION: A
      Schedule II controlled substance patient agreement was successfully implemented
      in a primary care practice reducing risk for both the patient and provider.

PMID- 29026751
TI  - Association of thyroid peroxidase antibody and dyslipidemia in subclinical
      hypothyroidism.
AB  - CONTEXT: Subclinical hypothyroidism (SCH) is stated as mild thyroid failure, is
      more common as compared to overt hypothyroidism, is associated with different
      biochemical abnormalities such as dyslipidemia, and is also having high
      conversion rate into overt hypothyroidism in patients having thyroid peroxidase
      (TPO) antibody positive. Lipid abnormalities are controversial in SCH and there
      is lack of Indian studies showing correlation between lipid abnormalities and TPO
      positivity in SCH. Hence, we did this study to find the TPO positivity and
      associated dyslipidemia in SCH patients. MATERIALS AND METHODS: It was a
      prospective observational study from January 2015 to December 2015 including
      fifty adult diagnosed SCH patients presented in outpatient department of Sri
      Balaji Action Medical Institute, Paschim Vihar, New Delhi. TPO positivity and
      different lipid abnormalities were studied in those fifty diagnosed SCH patients,
      and finally, association between TPO antibody and dyslipidemia was calculated.
      RESULTS: Females were predominant (86%). TPO was positive in 56% SCH patients.
      Dyslipidemia was found in 100% of SCH patients with positive TPO antibody. In
      overall, TPO positive patients as well as TPO positive females, total
      cholesterol, triglyceride, and low-density lipoprotein were significantly high
      while high-density lipoprotein was insignificant. In males, no significant
      association was found. CONCLUSION: In SCH patients, dyslipidemia is significantly
      associated with TPO positivity, especially in females. Hence, early screening,
      diagnosis, and treatment of SCH patients are recommended to prevent further
      risks.

PMID- 29026752
TI  - HWA: Hypoferritinemia without anemia a hidden hematology disorder.
AB  - INTRODUCTION: Anemia is a condition, in which the number of red blood cells (RBC)
      and the hemoglobin (Hb) is insufficient to meet the body's physiologic needs.
      Hypoferritinemia without anemia (HWA) could cause masked clinical manifestations
      as general weakness, easy fatigability, depressed mode, and hair loss but with
      normal complete blood count (CBC) parameters. HWA is deferent from iron
      deficiency anemia (IDA) because there is no reduction in the RBC, Hb, or any of
      the other parameters of the CBC. In HWA, the hypoferritinemia could be missed
      because serum ferritin not always requested by general practitioners. MATERIALS
      AND METHODS: A retrospective study conducted on 6993 patients of hypoferritinemia
      patients from our computerized database from 2010 to 2016. The parameters
      investigated to detect HWA disorder were serum ferritin, RBC, Hb, hematocrit,
      mean corpuscular volume, and mean corpuscular hemoglobin. RESULTS: HWA is found
      in 130 (0.018%) hypoferritinemia patients, in a ratio 1.7-1 females to male.
      CONCLUSION: HWA is a masked hematology disorder which needs new nomenclature to
      distinguish it from IDA because they are two deferent disorders although both of
      them have low serum ferritin. HWA is not a latent IDA because it could happen in
      patients whom will not get anemia as in polycythemia patients on recurrent
      veinesection treatement.

PMID- 29026753
TI  - Does violence affect the use of contraception? Identifying the hidden factors
      from rural India.
AB  - PURPOSE: The objective of this study is to investigates the relationship between
      domestic violence and use of contraception among married women in rural India.
      DATA: Third round of National Family Health Survey (NFHS-III). METHODOLOGY: Cross
      tabulation as bivariate analysis and Binary Logistic Regression as multivariate
      analysis has been employed to fulfill the objective. FINDINGS: The result shows
      that there are several hidden factors. between physical violence and
      contraception use. Alternate explanatory variables are significantly affected the
      use of contraception. With physical violence which reflects that there is a
      relationship between physical violence and socioeconomic status such as
      education, awareness, empowerment of women and subsequently the use of
      contraception. ORIGINALITY/VALUE: The paper throws light on the hidden factors
      which are obstacle in use of contraception with physical violence. Results of
      this study have potentially important implications for programs aimed at
      preventing violence and promoting family planning programs.

PMID- 29026754
TI  - Medication discrepancies and potentially inadequate prescriptions in elderly
      adults with polypharmacy in ambulatory care.
AB  - OBJECTIVES: The objective of this study is to describe the frequency and type of
      medication discrepancies (MD) through medication reconciliation and to describe
      the frequency of potentially inadequate prescription (PIP) medications using
      screening tool of older persons' prescriptions criteria. DESIGN: Cross-sectional
      comparison of electronic medical record (EMR) medication lists and patient's self
      report of their comprehensive medication histories obtained through telephone
      interviews. INCLUSION CRITERIA: Elderly individuals (>65 years old) with more
      than ten medications recorded in their EMR, who had not been hospitalized in the
      past year and were not under domiciliary care, affiliated to a private community
      hospital. OUTCOME MEASURES: The primary outcomes were the proportion of patients
      with MD and PIP. Secondary outcomes were the proportion of types of discrepancies
      and PIP. We analyzed possible associations between these variables and other
      demographic and clinical variables. RESULTS: Out of 214 randomly selected
      individuals, 150 accepted to participate (70%). The mean number of medications
      referred to be consumed by patients was 9.1 (95% confidence interval [CI] =8.6
      9.6), and the mean number of prescribed medications in their EMR was 13.9 (95% CI
      = 13.3-14.5). Ninety-nine percent had at least one discrepancy (total 1252
      discrepancies); 46% consumed at least one prescription not documented in their
      EMR and 93% did not consume at least one of the prescriptions documented in their
      EMR. In 77% of the patients, a PIP was detected (total 186), 87% of them were at
      least within one of the following categories: Prolonged used of benzodiazepines
      or proton pump inhibitors and the use of aspirin for the primary prevention of
      cardiovascular disease. CONCLUSIONS: There was a high prevalence of MD and PIP
      within the community of elderly adults affiliated to a Private University
      Hospital. Future interventions should be aimed at reducing the number of PIP to
      prevent adverse drug events and improve EMR accuracy by lowering medications
      discrepancies.

PMID- 29026755
TI  - Attitude toward learning of community medicine: A cross-sectional study among
      medical school students.
AB  - BACKGROUND: Community medicine strives to protect and promote the health and well
      being of the community through primary health care approach. However the
      preference of community medicine as career among medical school students and
      curriculum of community medicine is pivotal. AIM: The study intended to find the
      attitude towards learning of community medicine and also to assess the preference
      of post graduation specialty among medical school students. MATERIALS AND
      METHODS: A cross sectional study conducted at a teaching hospital located in
      Tamil Nadu, South India. The study questionnaire was administered to a total of
      500 study participants and the data collected were analyzed using SPSS IBM
      version 21.0. RESULTS: Almost 97% were of the opinion that community medicine
      subject is mandatory. Eighty three percent were interested in learning the
      principles. Only 21.8% students wanted to pursue post graduation in community
      medicine. Lack of attraction in terms of scientific technical interest, workplace
      conditions, and research potential has been reported for being not interested.
      CONCLUSION: Majority enjoyed to learn principles of community medicine at
      undergraduate curriculum but only few preferred to opt community medicine as post
      graduate specialty. Therefore there is a room to influence the medical students
      positively towards learning community medicine in curriculum.

PMID- 29026756
TI  - Gynecological complaints and their associated factors among women in a family
      health-care clinic.
AB  - AIM: The aim of this study was to describe the most common gynecological
      complaints and possible associated factors among women of reproductive age
      attended at a family health-care clinic. METHODOLOGY: A transversal study
      conducted with a sample of an outpatient population consisting of women of
      reproductive age. Pregnant women and minors were excluded. The final sample
      consisted of women between 18 and 49 years of age. The participants answered a
      questionnaire in which the complaints of the last 4 weeks were registered. They
      were examined, had the vaginal pH assessed, and secretion was tested using a 10%
      potassium hydroxide solution to verify the presence of amine odor (whiff test).
      RESULTS: Most participants were black or of mixed races. Considering the
      frequency of complaints, there were no significant differences between white and
      nonwhite women. There was an association between vaginal pH and discharge
      complaints as well as unpleasant odor, positive test of amines, smoking, and
      performing vaginal douches. CONCLUSIONS: Vaginal complaints were common among
      participants; the practice of vaginal douches was also frequent and was
      associated with higher pH values. The use of hormonal contraceptives was
      associated with lower pH values. There was no significant association between
      condom use and gynecological complaints, vaginal pH, or the whiff test.

PMID- 29026757
TI  - Socio-clinical profile of married women with history of induced abortion: A
      community-based cross-sectional study in a rural area.
AB  - BACKGROUND: Induced abortion contributes significantly to maternal mortality in
      developing countries yet women still seek repeat induced abortion in spite of the
      availability of contraceptive services. OBJECTIVES: (1) To study the
      sociodemographic profile of abortion seekers. (2) To study the reasons for
      procuring abortions by married women of reproductive age group. MATERIALS AND
      METHODS: It was a cross-sectional community-based study. All the married women of
      reproductive age group (15-49 years) with a history of induced abortion were
      selected as the subjects. RESULTS: The most common reason for seeking an abortion
      was poverty (39.4%), followed by girl child and husband's insistence, which
      accounted for 17.2% each. More complications were noted in women undergoing an
      abortion in places other than government hospitals and also who did it in the
      second trimester. CONCLUSIONS: To reduce maternal deaths from unsafe abortion,
      several broad activities require strengthening such as decreasing unwanted
      pregnancies, increasing geographic accessibility and affordability, upgrading
      facilities that offers medical termination of pregnancy (MTP) services,
      increasing awareness among the reproductive age about the legal and safe abortion
      facilities, the consequences of unsafe abortion, ensuring appropriate referral
      facilities, increasing access to safe abortion services and increasing the
      quality of abortion care, including postabortion care.

PMID- 29026758
TI  - Impact of school health education program on personal hygiene among school
      children of Lucknow district.
AB  - BACKGROUND: Personal hygiene plays a major role to promote healthy life. This
      study was performed to assess the current level of knowledge and practicing
      behavior in regard to hand washing, bathing, tooth brushing, and taking care of
      nail and hair. MATERIALS AND METHODS: A cross-sectional descriptive study was
      conducted on 800 students of Lucknow district. All the students were interviewed
      with a structured questionnaire (pretest). A visual display of good and bad
      personal hygiene was shown on projector and explained the benefits of good
      personal hygiene behavior. Again, structured questionnaire was given (posttest).
      RESULTS: Most of the students belonged to the 10-12 years age group. The
      knowledge of the students regarding general body cleanliness was 87.5% in
      posttest as compared to 53.8% in pretest. Keeping the hair well-trimmed was
      considered as a part of personal hygiene by 38.0% of students. Knowledge about
      eating less food in diarrhea was positive in 80% of students. Only 12.5% of
      students accepted that diarrhea can kill children (pretest) while 100% (posttest)
      children were aware of this fact. Practice regarding change of clothes was on
      alternate day in 79.5% of students. Most of the students were found washing their
      hair once a week (72.5%) and 70% students were washing hands before meal.
      CONCLUSION: Overall trend of knowledge and practice about personal hygiene was in
      poor condition among students at the time of pretest. Posttest results were
      highly satisfactory.

PMID- 29026759
TI  - Quality of life among elderly population residing in urban field practice area of
      a tertiary care institute of Ahmedabad city, Gujarat.
AB  - INTRODUCTION: Overall improvement in the living standards of country's population
      is leading to longer life expectancy. To emphasize the medical and psychological
      difficulties faced by geriatric people is essential to know status of their
      quality of life (QOL). METHODOLOGY: A community-based cross-sectional study was
      carried out at urban field practice area of one of the teaching institutes of
      Ahmedabad, Gujarat. Considering the prevalence of about 7.5% of 60 years and
      above people sample size of 250 was calculated. A predesigned questionnaire
      related to the QOL of elderly people devised by the World Health Organization-QOL
      was used. RESULTS: Mean age of the study population was 65.8 years with standard
      deviation of 5 years. Almost two-thirds of geriatrics were currently married and
      having spouse alive. List of common morbidities observed among study population
      was joint pain (42.8%), cataract (32.8%), hypertension (22.4%), diabetes mellitus
      (17.2%), and dental problems (12.4%). Scoring of QOL profile revealed that none
      of the geriatric had poor QOL, whereas 56% fall into category "good" and 50.8%
      had "excellent" QOL. QOL as per four different domains was significantly better
      among males as compared to females. Physical, environmental, and psychological
      domains were better in those who were educated and married individuals living
      with their spouse. CONCLUSION: Overall QOL was good to excellent. Social
      characteristics, such as education, marital status, and gender, all play role for
      the perceived QOL among the respondents.

PMID- 29026760
TI  - Etiological and clinicopathological study of secondary small vessel vasculitis in
      elderly: A case series of 12 patients.
AB  - BACKGROUND: Inflammation involving the postcapillary venular wall is defined as
      small vessel vasculitis. Small vessel vasculitis has various clinical
      manifestations. Etiologically, it can be primary or secondary. Literature
      regarding secondary vasculitis in elderly is scanty. AIM AND OBJECTIVES: In this
      case series, we aimed to assess the clinical features and etiologies of biopsy
      proven secondary small vessel vasculitis in the elderly. METHODOLOGY: Twelve
      elderly patients with biopsy-proven small vessel vasculitis were included in this
      study. All patients were thoroughly evaluated to assess the etiology and presence
      of major organ involvement. RESULTS: Secondary small vessel vasculitis involved
      both the sexes equally. Constitutional symptoms including fever and weight loss
      were noticed by most of the (70%) patients. Neurological deficits were present in
      83% of the study population. The most common finding in an electromyographic
      examination was an asymmetric sensory motor distal predominant polyradiculopathy.
      Fifty percent of the patients did fulfill the criteria for a definite autoimmune
      disease. More than 30% of the vasculitis was secondary to malignancies.
      CONCLUSIONS: Neurological manifestations are the most common systemic involvement
      in elderly patients with secondary vasculitis. Meticulous search for underlying
      malignancies is mandatory in elderly patients with secondary small vessel
      vasculitis.

PMID- 29026761
TI  - Postherpetic neuralgia, diabetic neuropathy, and trigeminal neuralgia - Chronic
      peripheral neuropathic pain in 58,480 rural Italian primary care patients.
AB  - INTRODUCTION: Chronic peripheral neuropathic pain (CPNP) is a condition due to
      peripheral nervous system diseases or injury, but its prevalence is unknown in
      Italian primary care. AIM: The aim of this study is to assess the prevalence of
      CPNP in a rural primary care area in Northern Italy. MATERIALS AND METHODS: A
      multicenter audit study was carried out in a rural area in Northern Italy with
      113 participating general practitioners (GPs) seeing 58,480 patients >18 years
      during 3 months. Patients who for any reason attended GPs' surgeries and had
      symptoms suggestive of neuropathic pain (NP) were given the NP diagnostic
      questionnaire "Douleur Neuropathique en 4 Questions" (DN4) and recorded their
      pain level on a visual analog scale (VAS). RESULTS: Chronic NP was established by
      a DN4 score of >=4 and a VAS pain score of >=40 mm for >6 months together with a
      clinical diagnosis in 448 (254 women and 194 men) out of 58,480 patients giving a
      prevalence of 0.77%. 179 patients (0.31%) had diabetes neuropathy, 142 (0.24%)
      had postherpetic pain, 41 (0.07%) had trigeminal neuralgia, 27 (0.05%) had NP
      postinjury, 27 (0.05%) had NP caused by nerve entrapments, 11 (0.02%) had NP
      triggered by systemic diseases, and 21 (0.04%) had NP of unknown etiology.
      CONCLUSIONS: The prevalence of CPNP in this population of primary care attenders
      in a rural area in Northern Italy was 0.77%. Diabetes neuropathy (0.31%) and
      postherpetic pain (0.24%) were the two most common subgroups of NP, followed by
      trigeminal neuralgia (0.07%).

PMID- 29026762
TI  - Correlation of Vitamin D with metabolic parameters in polycystic ovarian
      syndrome.
AB  - BACKGROUND: Polycystic ovarian syndrome (PCOS) and hypovitaminosis D are the two
      most common endocrine disorders in young women leading to many adverse metabolic
      consequences. We evaluated the correlation of 25-hydroxy Vitamin D (25OHD) with
      metabolic parameters and insulin resistance in PCOS. MATERIALS AND METHODS: We
      included 100 PCOS patients (age 18-40 years, duration >6 months) serially, in
      this cross-sectional study. We excluded patients with past use of insulin
      sensitizers and hormone therapy. All patients underwent a physical examination,
      body fat estimation, and a single fasting blood sample was analyzed for the
      biochemical parameters. The patients were divided into 2 groups as per the 25OHD
      level: Group 1 (Deficient, <30 ng/mL) and Group 2 (normal). The data were
      analyzed using appropriate statistical methods, and a P < 0.05 was considered
      statistically significant. RESULTS: The study population had a mean age of 28.6
      +/- 6.3 years, body mass index (BMI) 30.4 +/- 6.1 kg/m2 and body fat of 39.1 +/-
      13%. A total of 90 women had 25OHD deficiency, and hypovitaminosis D was observed
      more in younger, obese patients. Patients with hypovitaminosis D had a higher BMI
      (P = 0.0124), low- high-density lipoprotein (P = 0.0094), calcium (P <= 0.0001),
      and elevated testosterone (P = 0.0412) in comparison with normal 25OHD patients.
      None of the metabolic parameters showed significant correlation with 25OHD (P >
      0.05). CONCLUSION: Hypovitaminosis D is very common in PCOS patients and
      exacerbates the metabolic abnormalities. It is essential to screen all the PCOS
      patients for 25OHD deficiency, and further large-scale studies are required to
      confirm our findings.

PMID- 29026763
TI  - Comparative evaluation of Indian Diabetes Risk Score and Finnish Diabetes Risk
      Score for predicting risk of diabetes mellitus type II: A teaching hospital-based
      survey in Maharashtra.
AB  - CONTEXT: India is currently becoming capital for diabetes mellitus. This
      significantly increasing incidence of diabetes putting an additional burden on
      health care in India. Unfortunately, half of diabetic individuals are unknown
      about their diabetic status. Hence, there is an emergent need of effective
      screening instrument to identify "diabetes risk" individuals. AIMS: The aim is to
      evaluate and compare the diagnostic accuracy and clinical utility of Indian
      Diabetes Risk Score (IDRS) and Finnish Diabetes Risk Score (FINDRISC). SETTINGS
      AND DESIGN: This is retrospective, record-based study of diabetes detection camp
      organized by a teaching hospital. Out of 780 people attended this camp
      voluntarily only 763 fulfilled inclusion criteria of the study. SUBJECTS AND
      METHODS: In this camp, pro forma included the World Health Organization STEP
      guidelines for surveillance of noncommunicable diseases. Included primary
      sociodemographic characters, physical measurements, and clinical examination.
      After that followed the random blood glucose estimation of each individual.
      STATISTICAL ANALYSIS USED: Diagnostic accuracy of IDRS and FINDRISC compared by
      using receiver operative characteristic curve (ROC). Sensitivity, specificity,
      likelihood ratio, positive predictive and negative predictive values were
      compared. Clinical utility index (CUI) of each score also compared. SPSS version
      22, Stata 13, R3.2.9 used. RESULTS: Out of 763 individuals, 38 were new
      diabetics. By IDRS 347 and by FINDRISC 96 people were included in high-risk
      category for diabetes. Odds ratio for high-risk people in FINDRISC for getting
      affected by diabetes was 10.70. Similarly, it was 4.79 for IDRS. Area under
      curves of ROCs of both scores were indifferent (P = 0.98). Sensitivity and
      specificity of IDRS was 78.95% and 56.14%; whereas for FINDRISC it was 55.26% and
      89.66%, respectively. CUI was excellent (0.86) for FINDRISC while IDRS it was
      "satisfactory" (0.54). Bland-Altman plot and Cohen's Kappa suggested fair
      agreement between these score in measuring diabetes risk. CONCLUSIONS: Diagnostic
      accuracy and clinical utility of FINDRISC is fairly good than IDRS.

PMID- 29026764
TI  - A case-control study on environmental and biological risk factors for renal
      calculi persisting in a coastal Union Territory, India.
AB  - BACKGROUND AND OBJECTIVES: Renal stone disease is a common disorder of the
      urinary tract and also a significant problem because of incidence, recurrence,
      and severe consequences. The complex pathogenetic mechanisms of renal stone
      formation involve both biologic and environmental risk factors. The present study
      was performed to identify the role of these parameters among renal stone patients
      and normal individuals from a coastal union territory region in South India.
      METHODS: The authors conducted a case-control study of renal stone disease among
      outpatient department patients more than 30 years of age using systematic random
      sampling procedure with 100 study participants (50 subjects for each group). A
      questionnaire to explore some relevant history as well as to note general
      examination findings was used along with a house visit to collect a sample of
      water. Analysis was undertaken using appropriate statistical techniques. RESULTS:
      The study showed statistically significant association for renal stones with
      female sex, illiteracy, body mass index (BMI) (>25 kg/m2), sodium (>50 mg/L),
      water consumption (<1.5 L/day), water source being borewell, consuming soft
      drink, sedentary work, and family history of renal stones. The adjusted odds
      ratios (ORs) were significantly higher for consuming soft drink (OR: 8.19; 95%
      confidence interval: 1.99-33.69), sedentary work (10.01; 1.27-78.91), and water
      consumption < 1.5 L/day (7.73; 2.24-26.69). INTERPRETATION AND CONCLUSIONS: We
      conclude that in this part of India, female gender, illiteracy, high BMI, high
      sodium in drinking water, inadequate water consumption, borewell drinking water,
      soft-drink consumption, sedentary work, and family history of renal stones can
      lead to a significant increase in the risk of renal stone disease.

PMID- 29026765
TI  - Screening antenatal anxiety: Predicting its effect on fetal growth.
AB  - CONTEXT: Maternal anxiety has an association with low birth weight. However,
      studies are scarce to determine any association between maternal anxiety and
      fetal growth. AIMS: This study aims to determine the effect of maternal anxiety
      on fetal growth, measured by gestational age-dependent increase in fetal
      abdominal circumference (AC). The secondary objective is to determine the effect
      of maternal anxiety on other fetal parameters (biparietal diameter [BPD], head
      circumference [HC], femur length [FL]). SETTINGS AND DESIGN: This cross-sectional
      study was conducted in a tertiary care hospital, Kolkata. MATERIALS AND METHODS:
      Four hundred and ten pregnant mothers, between 14 and 40 weeks of gestation, were
      interviewed with socioeconomic and obstetric profile questionnaire and examined
      for anthropometric profile and presence and severity of pallor. Anxiety was
      assessed using Generalized Anxiety Disorder-7 (GAD) questionnaire. HC, AC, BPD,
      and FL were measured by ultrasound biometry. ANALYSIS USED: A multivariable
      logistic regression analysis was done to determine the predictors of small-for
      gestational-age (SGA). A robust mediation analysis was done to determine
      mediating effect of anxiety on gestational age-dependent increase in fetal AC.
      RESULTS: Mild (odds ratio [OR]Adjusted = 6.23, [2.41, 16.15]) and moderate
      (ORAdjusted = 22.42, [5.00, 100.57]) anxiety was significantly associated with
      SGA fetus. Anxiety increased with the progression of gestation (betaGAD: 0.011
      [0.007-0.015]) and it had a negative effect on fetal growth (standardized
      indirect effect of gestational age-mediated by anxiety on AC: -0.037 [-0.059, 
      0.022]). Anxiety also attenuated gestational age-dependent increment of HC.
      CONCLUSION: Mother's anxiety has a gestational age-dependent temporally
      incremental negative effect on fetal growth and brain development.

PMID- 29026767
TI  - Socioeconomic determinants affecting the quality of life among diabetic and
      hypertensive patients in a rural area, Egypt.
AB  - BACKGROUND: Diabetes mellitus and hypertension have a high prevalence of growth
      in all countries threatening to become a global epidemic risk, thus the quality
      of life this category of patients is extremely important. The aim of this study
      was to assess the socioeconomic determinants affecting the quality of life among
      diabetic and hypertensive patients. PATIENT AND METHODS: A descriptive cross
      sectional study was conducted in a rural family health care center in El-Batanon
      village, in the delta region of Menoufia, Egypt. The recruited sample population
      was 401 participants over six month's context time frame (diabetic and
      hypertensive participants were 224 and 117 respectively). All participants were
      interviewed using a questionnaire to assess the demographic characteristics,
      socioeconomic status, type, duration and treatments of illness and the 36-Item
      Short Form Health Survey. RESULTS: Patients with Diabetes presented a poorer
      health related quality of life than those with hypertension in perceived health
      in the areas of role-physical (RP) (P < 0.05), bodily pain (BP) (P < 0.001),
      general health (GH) (P < 0.05), vitality (VT) (P < 0.05), social functioning (SF)
      (P < 0.001) and role-emotional (RE) (P < 0.001). Age, Sex, Family size,
      socioeconomic score and occupation were the main Socioeconomic Determinants
      affecting the quality of life among diabetic and hypertensive patients.
      CONCLUSION: Diabetes and hypertension seem to comparably impair the health
      related quality of life. There is a need to develop and implement effective
      targeted intervention to help the patients to cope with their life in a better
      way.

PMID- 29026766
TI  - Hand hygiene knowledge of primary health care workers in Abha city, South Western
      Saudi Arabia.
AB  - PURPOSE: The aim of this is to find out the hand hygiene (HH) knowledge among
      primary health care workers (PHCWs) in Abha health district, southwestern Saudi
      Arabia. METHODS: Data were collected through an anonymous self-administered
      questionnaire. The questionnaire was based on a WHO "Knowledge Questionnaire for
      Health Care Workers." RESULTS: The study included 478 PHCWs (239 males and 239
      females). The sample included 186 physicians, 212 nurses, and 80 technicians. The
      highest proportion receiving formal training was nurses (82.1%). Females (77.4%)
      received significantly more training than males (70.3%). Only 59.2% (283) of the
      HCWs properly identified unclean hands of HCWs as the main route of the cross.
      Only 26.4% (126) of the HCWs properly identified germs already present on or
      within the patient as the most frequent source of pathogens in a health-care
      facility. Only 54.8% (262) of HCWs properly identified 20 s as the minimal time
      needed for alcohol-based hand rub to kill most germs on hands. CONCLUSION: The
      study revealed gaps in the knowledge regarding HH. To promote HH at primary
      health care setting, WHO bundle of multimodal strategies should be adopted
      including system change; training/education; evaluation and feedback; reminders
      in the workplace; and institutional safety climate.

PMID- 29026768
TI  - Macroglossia as a presenting feature of multiple myeloma.
AB  - Macroglossia has been very rarely reported as a first clinical sign of multiple
      myeloma.

PMID- 29026769
TI  - Increasing awareness of physicians against severe leptospirosis: A treatable but
      potentially fatal zoonotic infection.
AB  - Leptospirosis is a worldwide, often severe and potentially fatal zoonotic
      infection. Here, we present the case of a 35-year-old man with severe
      leptospirosis infection that was identified early and was treated effectively,
      with a quite impressive complete recovery. Delaying of early diagnosis and
      treatment is crucial for the development of an unfavorable clinical course and
      increases the risk of a lethal outcome.

PMID- 29026770
TI  - Coxsackie encephalitis in a child in Western India.
AB  - Enteroviral encephalitis in children has been rarely described from Western
      India. We describe a 51/2-year-old child with Coxsackie encephalitis.

PMID- 29026771
TI  - Aortoarteritis with tuberculosis.
AB  - Aortoarteritis is an inflammatory condition of the aorta, which has been rarely
      reported due to tuberculous infection. We report two cases of children who had
      aortoarteritis along with tuberculosis (TB), of which one had collapse
      consolidation and the other had latent TB. Both patients were treated with anti
      TB therapy and steroids.

PMID- 29026772
TI  - Lateral medullary syndrome after a scorpion sting.
AB  - Scorpion bites are a common problem in Southern parts of India. The sting of
      Mesobuthus tamulus belonging to the Buthidae family is known for being fatal. The
      toxidrome of scorpion sting is known for its effect on the cardiovascular system,
      and there have been rare reports of cerebrovascular accidents as well. We
      describe a case of lateral medullary syndrome secondary to scorpion sting. As per
      the knowledge of the authors, this is the first case report of the same.

PMID- 29026773
TI  - Neuroleptic malignant syndrome in a patient with stable dose of olanzapine.
AB  - Neuroleptic malignant syndrome (NMS), a potentially fatal consequence due to
      typical neuroleptics, has been described so far. In the past few years, there has
      been increased use of atypical antipsychotic drugs. Cases of NMS related to
      atypical neuroleptics, such as olanzapine, are less common in spite of increasing
      cases reported in literatures. Here, we report a case of NMS in a patient with
      bipolar affective disorder on maintenance treatment with 5 mg olanzapine for the
      last 7 year. He was successfully treated with bromocriptine and discharged in
      stable condition in 10 days.

PMID- 29026774
TI  - Atypical Kleine-Levin syndrome: An elusive entity?
AB  - Kleine-Levin syndrome (KLS) is a rare disorder (around 1.5 cases per million
      population), often presenting with triad of recurrent episodes of hypersomnia,
      hyperphagia, and hypersexuality. However, cases of atypical KLS with features
      opposite to that being commonly reported are often misdiagnosed as psychosis and
      present as a diagnostic challenge for the physicians, psychiatrists, and
      neurologists. We describe a case of atypical KLS which was misdiagnosed as
      unspecified nonorganic psychosis previously, highlighting the various points
      which would be helpful in identifying and diagnosing cases of atypical KLS in
      future.

PMID- 29026775
TI  - Hydatid disease: A rare cause of fracture nonunion.
AB  - Hydatid disease is an infrequent parasitic infestation caused by cestode, most
      commonly, Echinococcus granulosus. Bone involvement is distinctly uncommon. We
      would like to share our experience of a rare case of hydatid disease of femur in
      a 24-year-old male who presented with nonunion of subtrochanteric fracture.
      Histopathology showed typical lamellated wall and dagger-shaped hooklets. In view
      of its rarity, hydatid disease often remains an unsuspected infection of the
      bone.

PMID- 29026776
TI  - Antiepileptic therapy, osteomalacia, and synchronous fractures: Don't lose looser
      zones.

PMID- 29026777
TI  - Universal health coverage - There is more to it than meets the eye.

PMID- 29026778
TI  - Methods for estimating medication adherence to antiretroviral therapy: Response
      to Mehta et al. (2016).

PMID- 29026779
TI  - Oral rehydration solution in infantile diarrhea: Make sure it is given properly!

PMID- 29026780
TI  - Status of Iran's Primary Health Care System in Terms of Health Systems Control
      Knobs: A Review Article.
AB  - BACKGROUND: After the establishment of Primary Health Care (PHC) program in Iran,
      health indicators have improved every year. This progress was so rapid that a
      number of shortcomings and weaknesses of the PHC program remained silent behind
      its successes. This study aimed to assess the status of Iran's PHC system
      (strengths, weaknesses, opportunities and threats) in terms of health system's
      control knobs. METHODS: The search was conducted through two English 'databases
      of Web of Knowledge and PubMed, two English publications of Science Direct and
      Springer and two Persian databases of Magiran and SID. Keywords were selected
      from MeSH and included primary health care, PHC and Iran in both Persian and
      English. No time limit was considered. RESULTS: Iran's PHC system has numerous
      successes in dealing with health system's control knobs; which largely part of
      that related to the health network implementation, the role of Behvarz,
      improvement of health indicators in rural areas and the elimination of urban
      rural inequality, but there are some weaknesses, opportunities and threats in the
      Iranian PHC system as well. CONCLUSION: By considering socio-economic changes the
      current structure of PHC system needs to be reformed to coordinate with
      phenomenon of chronic diseases, accidents and aging. The current information
      system in PHC does not provide the required information for decision makers and
      policy makers so it needs to be transformed to the electronic system with unique
      electronic health file for individuals.

PMID- 29026781
TI  - Bulge Region as a Putative Hair Follicle Stem Cells Niche: A Brief Review.
AB  - BACKGROUND: Hair follicle stem cells exist in different sites. Most of the hair
      follicle stem cells are reside in niche called bulge. Bulge region is located
      between the opening of sebaceous gland and the attachment site of the arrector
      pili muscle. METHODS: Data were collected using databases and resources of
      PubMed, Web of Science, Science Direct, Scopus, MEDLINE and their references from
      the earliest available published to identify English observational studies on
      hair follicle bulge region. RESULTS: Bulge stem cells are pluripotent with high
      proliferative capacity. Specific markers allow the bulge cells to be isolated
      from mouse or human hair follicle. Stem cells isolated from bulge region are
      label retaining and slow cycling hence these cells are defined as label-retaining
      cells. Bulge cell populations, due to their plasticity nature are able to
      differentiate into distinct linage and could contribute in tissue regeneration.
      CONCLUSION: The current review discuss about bulge stem cells characteristics and
      biology including their cycle, location, plasticity, specific markers and
      regenerative nature. Also the differences between mouse and human hair follicles
      are investigated.

PMID- 29026783
TI  - Knowledge and Practice on Malaria among Korean Soldiers in Nearby Demilitarized
      Zone in South Korea.
AB  - BACKGROUND: The aim of this study was to provide evidence for developing
      intervention and effective management for the prevention of malaria based on
      epidemiological analysis and assessment of Korean soldiers' knowledge on malaria
      and malaria preventive behavior. METHODS: The data were collected from 294 Korean
      soldiers nearby the demilitarized zone in Gyeonggi Province in 2016. Multiple
      regression analyses were applied for statistical analysis. RESULTS: The level of
      education (beta=.24, P<.001), educational experience on malaria (beta=.21,
      P<.001) and ranks like corporal (beta=.13, P<.05), and sergeant (beta=.13, P<.05)
      were observed to be associated with the level of knowledge of malaria (F=9.62,
      R2=.12, P<.001). Knowledge of malaria (beta=.25, P<.001) and malaria education
      experience (beta=.22, P<.001) were the factors that influenced malaria prevention
      behavior and practice (F=12.45, R2=.18, P<.001). CONCLUSION: The level of
      knowledge and education experience was associated with malaria prevention
      practice. Therefore, malaria education is very important for the soldiers in
      nearby DMZ for prevention of malaria. The findings provide implications for the
      development of intervention programs focusing on increasing the levels of
      knowledge and practices related to malaria.

PMID- 29026782
TI  - Bentonite Clay as a Natural Remedy: A Brief Review.
AB  - BACKGROUND: From old times, the human kind has used clays, externally or
      internally, for maintaining body health or treating some diseases. Meanwhile
      there are few scientific articles reviewing the beneficial effects of clays on
      body function. Bentonite clay is one of the available clays in nature, used as
      traditional habits, and remedies in many cultures. METHODS: These articles
      explored among 2500 scientific articles published in PubMed to sort the
      scientific works have been done on the effects of this clay on body function (it
      was about 100 articles). RESULTS: Bentonite has a broad range of action on
      different parts of body. CONCLUSION: As traditional remedies seem to have a deep
      root in maintaining body health, it merits doing more research works on bentonite
      clay and its impacts on body function.

PMID- 29026784
TI  - Effects of Medical Insurance on the Health Status and Life Satisfaction of the
      Elderly.
AB  - BACKGROUND: Population aging has become increasingly serious in China. The demand
      for medical insurance of the elderly is increasing, and their health status and
      life satisfaction are becoming significant issues. This study investigates the
      effects of medical insurance on the health status and life satisfaction of the
      elderly. METHODS: The national baseline survey data of the China Health and
      Retirement Longitudinal Survey in 2013 were adopted. The Ordered Probit Model was
      established. The effects of the medical insurance for urban employees, medical
      insurance for urban residents, and new rural cooperative medical insurance on the
      health status and life satisfaction of the elderly were investigated. RESULTS:
      Medical insurance could facilitate the improvement of the health status and life
      satisfaction of the elderly. Accordingly, the health status and life satisfaction
      of the elderly who have medical insurance for urban residents improved
      significantly. The regression coefficients were 0.348 and 0.307. The
      corresponding regression coefficients of the medical insurance for urban
      employees were 0.189 and 0.236. The regression coefficients of the new rural
      cooperative medical insurance were 0.170 and 0.188. CONCLUSION: Medical insurance
      can significantly improve the health status and life satisfaction of the elderly.
      This development is of immense significance for the formulation of equal medical
      security.

PMID- 29026785
TI  - Evaluation of p16INK4alpha Hypermethylation from Liquid-based Pap Test Samples in
      Vietnamese Population.
AB  - BACKGROUND: Human papillomavirus (HPV) infection has been considered as main
      cause of cervical cancer. Recently, aberrant DNA methylation at tumor suppressor
      genes (TSGs), leading to inactivation, has also been an early epigenetic event
      and cofactor in cervical carcinogenesis. This study was performed to evaluate an
      association between the hypermethylation of p16INK4alpha gene's promoter and HPV
      exposure in non-invasive samples (liquid-based papanicolaous samples) in
      Vietnamese population. METHODS: 109 liquid-based papanicolaous test samples were
      archived and admitted from the Medic Medical Center and Au Lac Clinic Laboratory,
      Vietnam, from 2011-2014. Methylation-Specific-PCR (MSP) was performed to analyze
      methylation status from the liquid-based papanicolaous test samples identified
      whether HPV/or non-HPV, high-risk/low-risk HPV infection. RESULTS: An upward
      trend was observed concerning the p16INK4alpha hypermethylation frequency in high
      risk HPV infection, counting for 55.6%, and the low methylation frequency in low
      risk and non-HPV infected samples, counting for 22.9%, 8.0%, respectively. The
      significant correlation between candidate p16INK4alpha hypermethylation and HPV
      exposure was observed (P<0.0001). Moreover, the odds ratio (OR) and relative risk
      (RR) were found in statistical significant value. (OR=5.76, 95%CI: 2.36 - 14.04,
      P<0.01; RR=3.11, 95%CI: 1.75-5.53, P<0.01). CONCLUSION: Presence of p16INK4alpha
      hypermethylation was the specific characteristic of high-risk HPV infected
      samples in Vietnamese population. The OR and RR values showed that the strong
      correlation between p16INK4alpha hypermethylation and high-risk HPV infection, in
      which increased the risk of cervical cancer. The combination of p16INK4alpha
      hyper-methylation and HPV detection based biomarker could be used in non-invasive
      samples obtained from high-risk cancer patients, offer significant practical
      advantages.

PMID- 29026786
TI  - The Relationship between Type 2 Diabetes and Platelet Indicators.
AB  - BACKGROUND: Currently, the studies on the relationship between type 2 diabetes
      and platelets indicators were carried out on a selective small sample population
      generally. Large sample studies in this area are rare, especially in Chinese
      population. In this study, we aimed to investigate the relationship between type
      2 diabetes and the mean platelet volume (MPV), platelet count (PLT) and platelet
      distribution width (PDW). METHODS: This is a cross-sectional analysis of the
      routine health examination data from 20128 participants with complete baseline
      data in Yinzhou District 2013. The detection of indicators in this study was
      completed by automatic hematology analyzer. RESULTS: The PDW and PLT were not
      significantly different between diabetic group and non-diabetic group, (16.00%
      vs. 16.00%, P=0.88, and 194*109/L vs. 196*109/L, P=0.05 respectively). The MPV
      was significantly higher in diabetic group (9.3fl vs. 9.2fl, P<0.05). MPV was an
      independent risk factor of diabetes mellitus (Unadjusted OR=1.07 (95% CI: 1.03,
      1.11), Adjusted for age, sex OR=1.07 (95% CI: 1.02, 1.12)). The adjusted odds
      ratio of diabetes rose with increasing MPV levels and were most pronounced in
      subjects with MPV levels exceeding the 90th percentile (MPV >=10.70 fl, Crude
      or=1.23 adjusted or=1.19). CONCLUSION: There was no relationship between the
      presence of diabetes with PDW and PLT. The MPV was independently associated with
      the presence of diabetes.

PMID- 29026787
TI  - Factors Determining Effective Orthokeratology Treatment for Controlling Juvenile
      Myopia Progression.
AB  - BACKGROUND: We aimed to identify factors influencing the therapeutic outcome of
      orthokeratology on controlling juvenile myopia progression, and the risk factors
      for complications. METHODS: Myopic patients (n=724) in Shenzhen Second Hospital
      from Jan 2011 to Jan 2016 fitted with orthokeratology lenses and followed-up for
      6-65 months were reviewed retrospectively. Univariate and multivariate logistic
      regression analyses were used to screen for the factors that can improve
      treatment outcome and prevent the development of complications. RESULTS: Patients
      where the orthokeratology treatment was effective displayed a shorter myopia
      time, smaller diopter and corneal curvature, larger corneal endothelium density,
      high proportion of overnight wear and longer wearing times compared with patients
      whose treatments were ineffective. Additionally, wearing Ortho-k for 6 or 12
      months yielded improved corrective effect and achieved higher comfort level.
      Logistic regression analyses showed that myopia time, diopter, corneal curvature
      e value, corneal endothelium density, time with Ortho-k and corrective effect
      after wearing Ortho-k for 6 or 12 months were all independent factors influencing
      the treatment effects. Results showed corneal curvature, anterior chamber depth
      and central corneal thickness were independent risk factors. CONCLUSION: This
      study systematically identified the factors leading to effective treatments, and
      those carrying a risk for complications, to provide guidance for the prescription
      and follow-up of orthokeratology in the treatment of juvenile myopia.

PMID- 29026788
TI  - Trends in Antimicrobial Prescription for Inpatients in Changsha, China, 2003 to
      2014.
AB  - BACKGROUND: China had implemented policies to limit antimicrobials prescription
      since 2004; we conducted this study to reflect the effect of these national
      policies by analyzing antimicrobial prescription trends of medical insurance in
      patients from 2003 to 2014 in Changsha city, China. METHODS: The participants
      were inpatients of the medical insurance of urban workers (UEBMI). Data were
      extracted from medical insurance information system of Changsha Medical Insurance
      Institution, which directly connects with hospitals information systems. RESULTS:
      Trend analysis showed great changes in antimicrobial prescription and inpatients'
      cost on antimicrobials over the study period. Antimicrobial prescription rates
      gradually declined over the study period from 79.0% in 2003 to 43.5% in 2014
      (adjusted OR0.205; 95%CI 0.198 to 0.213). There was a quicker decline from 2011
      to 2014 (with implementing national antimicrobial stewardship action plan) than
      the period from 2003 to 2010 (with implementing antimicrobials use education and
      self-management strategies). The proportion of inpatients used one antimicrobial
      increased significantly from 25.6% in 2003 to 46.7% in 2014, while the proportion
      of inpatients used three or more antimicrobials gradually decreased. Bacterial
      culture rate increased from 20.4% in 2003 to 36.6% in 2014 (adjusted OR 2.248;
      95% CI 2.149 to 2.352). The average costs on antimicrobials decreased
      significantly, from 277.43 US Dollar in 2003 to 91.05 US Dollar in 2014.
      CONCLUSION: National efforts to promote rational use of antimicrobials in
      clinical practice have had a positive effect over the past decade in China.

PMID- 29026789
TI  - The Impact of the Predictive Nursing Education Process on Degree of Comfort and
      Quality of Life for Patients in the Oncology Department.
AB  - BACKGROUND: We investigated the application of a predictive nursing education
      process on the degree of comfort and quality of life for cancer patients.
      METHODS: A total of 168-cancer patient in Zhujiang Hospital of Southern Medical
      University, Guangzhou, Guangdong, China between June 2014 and June 2016 were
      enrolled and admitted for surgery or radiotherapy/chemotherapy treatment.
      Patients were randomly divided into control and observation groups, each
      containing 84 cases. Patients in the control group received routine cancer care,
      whereas the observation group received care incorporating a predictive nursing
      education process. Patients were assessed after admission and prior to discharge
      via the Kolcaba's comfort status scale (through a General Comfort Questionnaire
      (GCQ)), quality of life scale (QOL), and Barthel Index (BI) for activities of
      daily living (ADL). Patient mental state was also evaluated using the Hamilton
      Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). RESULTS:
      GCQ, QOL, and BI scores of the observation group were all significantly higher
      than those of the control group (P <0.05). HAMA and HAMD scores were
      significantly lower in the observation group compared to the control group (P <
      0.05). CONCLUSION: The predictive nursing education process could significantly
      improve degree of comfort and activities of daily living for cancer patients, and
      thus improve mental states and quality of life.

PMID- 29026791
TI  - Willingness to Pay for Complementary Health Care Insurance in Iran.
AB  - BACKGROUND: Complementary health insurance is increasingly used to remedy the
      limitations and shortcomings of the basic health insurance benefit packages.
      Hence, it is essential to gather reliable information about the amount of
      Willingness to Pay (WTP) for health insurance. We assessed the WTP for health
      insurance in Iran in order to suggest an affordable complementary health
      insurance. METHODS: The study sample consisted of 300 household heads all over
      provinces of Iran in 2013. The method applied was double bounded dichotomous
      choice and open-ended question approach of contingent valuation. RESULTS: The
      average WTP for complementary health insurance per person per month by double
      bounded dichotomous choice and open-ended question method respectively was 199000
      and 115300 Rials (8 and 4.6 USD, respectively). Household's heads with higher
      levels of income and those who worked had more WTP for the health insurance.
      Besides, the WTP increased in direct proportion to the number of insured members
      of each household and in inverse proportion to the family size. CONCLUSION: The
      WTP value can be used as a premium in a society. As an important finding, the
      study indicated that the households were willing to pay higher premiums than
      currently collected for the complementary health insurance coverage in Iran. This
      offers the policy makers the opportunity to increase the premium and provide good
      benefits package for insured people of country then better risk pooling.

PMID- 29026790
TI  - The Prevalence of Hearing Impairment by Age and Gender in a Population-based
      Study.
AB  - BACKGROUND: This study aimed to determine the prevalence of hearing impairment
      (HI) by age and gender in a population aged 5 yr and older residing in Tehran,
      Iran. METHODS: In this cross-sectional study, 140 clusters each including 10
      households from Tehran, Iran were sampled between 2012 and 2013 using cluster
      random sampling. Trained audiologists examined the participants during face-to
      face interviews. The hearing of the participants was evaluated before the removal
      of wax or other foreign bodies. In this study, HI was categorized as mild (grade
      1, 26-40 db), moderate (grade 2, 41-60 db), severe (grade 3, 61-80 db), and deaf
      (grade 5, 81 db or more). All participants signed informed consent forms. The
      SATA software was used for data analysis. RESULTS: Of 6521 individuals, 4370
      (67%) were interviewed. The prevalence of HI (auditory threshold of 0.5, 1, 2, 4
      KHz and more than 25 db in the better ear) was 14.27 (11.53-17.91) of whom 9.52
      (7.07-11.98) had grade 1, 4.04 (3.02-5.06) had grade 2, 0.67 (0.33-1.02) had
      grade 3 HI and 0.48 (0.16-0.8) were deaf. About 5.19% of the participants had
      disabling hearing impairment. All HI grades increased significantly with age but
      no significant difference was observed between men and women. CONCLUSION: The
      considerable prevalence of HI in Iran in comparison with other developing
      countries, with regards to the trend of aging in the population, seems
      concerning. The results of the study could be used as a treatment and research
      guideline for future works in the area of policymaking and plan to decrease these
      disorders.

PMID- 29026792
TI  - Antiretroviral Drug Resistance Mutations among HIV Treatment Failure Patients in
      Tehran, Iran.
AB  - BACKGROUND: This study aimed to determine drug resistance mutations in patients
      with virological failure and find correlation between HIV drug resistance test
      and viral load. METHODS: Blood sample was collected from 51 patients who
      suspicious treatment failure in the center of Imam Khomeini Hospital, Tehran,
      Iran in 2015. Viral voluntary counseling and testing load test was done and the
      patients with viral load above 1000 copies choose for detection of drug
      resistance mutations by genotyping method (29 patients). RESULTS: The majority of
      patients (82.75) harbored the HIV subtype CRF 35 A-D. The 86.2% patients
      compromised at least one resistance mutation. The analysis of reverse
      transcriptase showed M184V (68.9%), T215YISF (44.8%), K103N (27.6%) and the
      analysis results of protease revealed G73SC (13.8%) and I47VA (6.9%). Eventually,
      the significant correlation between viral load and drug resistance was found.
      CONCLUSION: The result of our research stress the significance of recognizing
      drug resistant on time that prohibits the accumulation of drug resistance
      mutation and circulates the resistance strain of HIV-1 virus and the importance
      of national study according to the reliable findings for treatment guidelines.

PMID- 29026793
TI  - Sexual Function, Mental Well-being and Quality of Life among Kurdish Circumcised
      Women in Iran.
AB  - BACKGROUND: Female genital mutilation is an intentional inhumane procedure that
      threatens girls and women's health. It is especially widespread in developing
      countries due to cultural, traditional and religious preferences. The aim of the
      current study was to investigate how circumcision affects women's sexual
      function. METHODS: This cross-sectional study was conducted in the urban and
      rural area of Piranshahr County, Iran, in 2015 among convenience samples of 200
      women, 15-49 yr old, who were applying to health care centers for receiving
      routine health care services. Data collection was conducted with the use of a
      self-administered written questionnaire to assess female sexual function, mental
      well-being, and quality of life. RESULTS: Significant differences were found
      between circumcised and non-circumcised women in total score of female sexual
      function index (FSFI) in domains of desire, arousal, vaginal moisture, orgasm,
      satisfaction, and pain [(P<0.001), MD(95%CI)=5.64(3.64 to 7.64)] and based on
      Hotelling's T-square, significant differences were found in dimensions of quality
      of life and FSFI. CONCLUSION: The revealed sexual dysfunction among mutilated
      women gives ground to require that public health systems take actions aimed at
      implementing special sexual education program to improve sexual functions of
      mutilated women and changing beliefs and social norms in the community level.

PMID- 29026794
TI  - Nitrite and Nitrate Concentrations in the Drinking Groundwater of Shiraz City,
      South-central Iran by Statistical Models.
AB  - BACKGROUND: Nitrite (NO2-) and nitrate (NO3-) contaminations of groundwater are
      considered as one of the major health challenges in recent decades. This study
      aimed to evaluate the nitrite and nitrate concentrations in the drinking
      groundwater of Shiraz, South-central Iran by statistical models. METHODS: From 43
      active wells of Shiraz drinking water supplies, 344 samples were collected in the
      high and low precipitation seasons from 2010 to 2014. Nitrate and nitrite
      concentrations were tested by a DR6000 spectrophotometer, and the results were
      analyzed by different software, including SPSS ver. 20, ArcView GIS 9.3. It was
      done by variable and multivariate regression models. In all tests, the level of
      significance was set at 5%. RESULTS: Nitrate concentrations in the samples were
      in the range of 5 to 72 mg/l, and 38 (11%) of the samples had nitrate
      concentrations above the standard level 10 mg/L as nitrogen. The annual mean
      concentration of nitrite varied from 0 to 0.025 mg/l. There was an inverse
      correlation between nitrate and nitrite concentrations and well depths.
      CONCLUSION: The most important reason for the high concentration of nitrate in
      Shiraz drinking groundwater supplies were lack of health privacy of wells, the
      impact of residential construction around drinking water wells, and placement of
      wells in the direction of groundwater flow.

PMID- 29026796
TI  - Effects of the CrossFit Exercise Data Analysis on Body Composition and Blood
      Profiles.

PMID- 29026795
TI  - The Prevalence of Plasmid-mediated Quinolone Resistance Genes in Escherichia coli
      Isolated from Hospital Wastewater Sources in Tehran, Iran.
AB  - BACKGROUND: Considering the importance of hospital wastewaters as potential
      reservoirs for the dissemination of bacterial pathogens such as Escherichia coli
      and antibiotic resistance genes in the environment, the need for such information
      becomes imperative. METHODS: E. coli strains were isolated from hospital
      wastewater sources in Tehran, Iran, over a 24-month sampling period (Jun 2014-
      Jun 2016) and identified using standard bacteriological methods. Quinolone
      resistance among the strains was determined using Kirby-Bauer method and the
      frequency of plasmid-mediated quinolone resistance genes (qnrA, qnrB, qnrS) was
      investigated by PCR. RESULTS: In total, 80 E. coli strains were isolated during
      the study period, of which 51 (63.8%) isolates were resistant to tested
      antibiotics. Of note, 13 isolates were resistant to all the antibiotics employed.
      The highest rates of antibiotic resistance were obtained for nalidixic acid
      (60%), followed by norfloxacin (30%), and ciprofloxacin (25%). Of the 51
      quinolone-resistant strains, 24 (47.1%) isolates harbored qnr genes. None of the
      isolates harboured the qnrA gene, while 11 (45.8%) and 7 (29.2%) isolates
      contained qnrB and qnrS, respectively. CONCLUSION: Our findings showed high rates
      of quinolone resistance (63.8%) and qnr genes, underlining the importance of
      hospital wastewaters as reservoirs for dissemination of potentially pathogenic E.
      coli and horizontal gene transfer between other waterborne bacterial species.
      Other possible mechanisms of resistance should also be investigated for better
      characterization of quinolone-resistant E. coli isolates.

PMID- 29026797
TI  - The Treated Drug Users in the Slovak Republic.

PMID- 29026798
TI  - Influence of Youth Baseball Players' Pitches on Range of Motion and Ball Speed.

PMID- 29026799
TI  - Perceived Health Related Quality of Life Outcomes with Silicosis Patients.

PMID- 29026800
TI  - Pediculosis in School Sitting: What Is the Role of School Nurses?

PMID- 29026801
TI  - Suicide: An Un-resolved and Under-recognized Health Problem among People of Ilam
      Province (The Most Popular Suicide Spot in Iran).

PMID- 29026802
TI  - Sexual Transmission of Zika Virus: An Assessment of the Evidence.

PMID- 29026803
TI  - Primary Health Care: An Important Approach for Health Sector, Missed in Iran's
      Health System Evolution Plan.

PMID- 29026805
TI  - Editorial.

PMID- 29026804
TI  - The effect of cardamom supplementation on serum lipids, glycemic indices and
      blood pressure in overweight and obese pre-diabetic women: a randomized
      controlled trial.
AB  - BACKGROUND: Spice consumption helps the treatment of diseases due to their
      antioxidant and anti-inflammatory contents. Cardamom is one of this spices;
      therefore, this study is designed to determine the effect of cardamom
      supplementation on serum lipids, glycemic indices, and blood pressure in pre
      diabetic women. METHODS: Eighty overweight or obese pre-diabetic women were
      randomly allocated to two groups. The intervention group received 3 g of green
      cardamom and the placebo group received 3 g of rusk powder for 2 months. The
      physical activity level, dietary intake, anthropometric measurements, Blood
      pressure, fasting blood sugar (FBS), triglyceride (TG), total cholesterol (TC),
      low density lipoprotein (LDL-C), high density lipoprotein (HDL-C), insulin, body
      mass index (BMI), insulin resistance, and insulin sensitivity were measured
      before and after intervention. RESULTS: After intervention, mean TC (p = 0.02)
      and LDL-C (p = 0.01) significantly decreased and insulin sensitivity (p = 0.03)
      increased in the cardamom group. In the control group, mean HDL-C (p = 0.02)
      significantly decreased after the study. We observed no significant decrease in
      systolic and diastolic blood pressure, glycemic indices, and serum lipids values
      in the cardamom group compared to the placebo group. CONCLUSIONS: Green cardamom
      supplementation may have a protective effect on HDL-C level in pre-diabetic
      subjects. It improves some blood parameters in these subjects; however, its
      effects are not different from placebo. TRIAL REGISTRATION: Iranian Registry of
      Clinical Trials, IRCT2014060817254N2. Registered 2 September 2014.

PMID- 29026806
TI  - A Tale of Two Health-Care Systems: Cost-Utility Analysis of Open Carpal Tunnel
      Release in Canada and the United States.
AB  - PURPOSE: Canadian health care is often criticized for extended wait times,
      whereas the United States suffers from increased costs. The purpose of this pilot
      study was to determine the cost-utility of open carpal tunnel release in Canada
      versus the United States. METHODS: A prospective cohort study evaluated patients
      undergoing open carpal tunnel release at an institution in Canada and the United
      States. All costs from a societal perspective were captured. Utility was measured
      using validated health-related quality of life (HRQOL) scales-the EuroQol-5D and
      the Michigan Hand Outcome Questionnaire. RESULTS: Twenty-one patients at the
      Canadian site and 8 patients at the US site participated. Mean total costs were
      US $1581 +/- $1965 and $2179 (range: $1421-$2741) at the Canadian and US sites,
      respectively. Health-related quality of life demonstrated significant
      improvements following surgery (P < .05). Patient utilities preoperatively and at
      6 weeks and 3 months postoperatively were 0.72 +/- 0.20, 0.86 +/- 0.11, and 0.83
      +/- 0.16 at the Canadian site and 0.81 +/- 0.09, 0.86 +/- 0.10, and 0.86 +/- 0.12
      at the US site. Improvements in HRQOL directly related to surgery were not
      significantly different between patients in Canada and the United States.
      American patients, however, attained improved HRQOL sooner due to shorter wait
      times (27 +/- 10 vs 214 +/- 119 days; P < .001). The incremental cost-utility of
      the US system was $7758/quality-adjusted life year gained compared to the
      Canadian system. Sensitivity analyses confirmed that these results were robust.
      CONCLUSION: This pilot study suggests that carpal tunnel surgery is more cost
      effective in the United States due to prolonged wait times in Canada.

PMID- 29026807
TI  - Airway Management in Pierre Robin Sequence: The Vancouver Classification.
AB  - BACKGROUND: Pierre Robin sequence (PRS) is a triad of micrognathia, glossoptosis,
      and respiratory distress. There is no standard clinical classification used in
      the management of neonatal airway in patients with PRS. The goal of our study was
      to review the presentation and management of patients with PRS and formulate a
      clinical grading system and treatment algorithm. METHODS: A 10-year retrospective
      review of all neonates diagnosed with PRS was performed after obtaining
      institutional ethics approval. Patients were identified using our cleft lip and
      palate program database. Inclusion criteria were 2 of the following 3 clinical
      features-glossoptosis, retrognathia, or airway obstruction. We collected
      demographic data, clinical information (coexisting airway morbidity, maxillary
      mandibular discrepancy, type of intervention used, complications, and outcomes
      (feeding, length of stay, and airway status) during the first year of life.
      RESULTS: Sixty-three patients met our inclusion criteria. Of these, 55 (87%) had
      cleft palate and 17 (27%) were syndromic. Forty-eight (76%) patients were managed
      by prone positioning. Of the 15 surgically managed patients, the initial
      procedure was floor of mouth release in 7, mandibular distraction osteogenesis
      (MDO) in 4, and tongue-lip adhesion in 4. Five patients with coexisting airway
      morbidity needed a second surgery; 2 had MDO and 3 tracheostomies (one patient
      was later decannulated). Seven (47%) of the surgically managed patients required
      a gastrostomy tube. CONCLUSION: At present, there is no consensus on neonatal
      airway management in infants with PRS. From our review of 63 patients with PRS,
      we hereby propose a simple 4-point classification system and treatment algorithm,
      based on clinical features.

PMID- 29026808
TI  - Low-Frequency Ultrasound Debridement in Chronic Wound Healing: A Systematic
      Review of Current Evidence.
AB  - Chronic wounds are painful and debilitating to patients, pose a clinical
      challenge to physicians, and impose financial burden on the health-care system.
      New treatment options are therefore highly sought after. Ultrasound debridement
      is a promising technology that functions to disperse bacterial biofilms and
      stimulate wound healing. In this review, we focus on low-frequency ultrasound (20
      60 kHz) and summarize the findings of 25 recent studies examining ultrasound
      efficacy. Ultrasound debridement appears to be most effective when used 3 times a
      week and has the potential to decrease exudate and slough, decrease patient pain,
      disperse biofilms, and increase healing in wounds of various etiology. Although
      current studies are generally of smaller size, the results are promising and we
      recommend the testing of low-frequency ultrasound therapy in clinical practice on
      a larger scale.

PMID- 29026809
TI  - Spontaneously Resolved Macrocystic Lymphatic Malformations: Predictive Variables
      and Outcomes.
AB  - INTRODUCTION: Lymphatic malformations are benign, low-flow vascular malformations
      that typically present at or near birth. Due to morbidity associated with
      operative treatment, nonoperative treatment with injection of sclerosant has
      become the mainstay of therapy. Over the past 15 years, several patients at our
      centre with macrocystic (>2 cm cyst size) lymphatic malformations have seen their
      lesions resolve spontaneously while awaiting treatment. In this study, we review
      features of these patients that may contribute to spontaneous resolution. METHOD:
      A retrospective chart review was conducted from our Vascular Anomalies Clinic
      database (1999-2014) of all macrocystic lymphatic malformations; characteristics
      of patients with spontaneous resolution were reviewed. RESULTS: Of 61 patients
      with macrocystic lymphatic malformations, 7 cases (11.5%; 4 females, 3 males)
      resolved spontaneously. Median age at malformation appearance was 2 years (range:
      0-6.5 years), with median age at resolution of 4 years (range: 10 months-7
      years). Median time from appearance to resolution was 24 months (range: 3-43
      months), with a median follow-up time of 4 years (range: 1-15 years). All but 1
      case was associated with local or upper respiratory tract infection antecedent to
      resolution. Six of the 7 lesions were located in the neck. CONCLUSION: Among the
      cases reviewed, there was a common theme of upper respiratory tract or local
      infection antecedent to spontaneous lesion resolution. Compared to the
      literature, our proportion of malformations presenting after birth and the
      proportion of malformations presenting in the neck region were higher than those
      of other series. Although side effects associated with treatment are generally
      mild and/or rare, risks related to sclerotherapy and the accompanying requirement
      for general anesthesia in pediatric populations nevertheless exist. As the median
      time from lesion appearance to resolution was 24 months, it may be reasonable to
      observe these malformations for up to 24 months before proceeding with treatment
      if the lesion does not impair function and disfigurement is not considerable,
      particularly if the lesion presents after birth and/or is located in the neck
      region.

PMID- 29026810
TI  - The Role of Local Bupivacaine Irrigation in Postoperative Pain Control After
      Augmentation Mammoplasty: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: The objective of this study is to analyze the efficacy of local
      bupivacaine irrigation after augmentation mammoplasty for the control of
      postoperative pain. METHODS: A systematic review and meta-analysis was conducted
      including all randomized controlled trials (RCTs) that compared the irrigation of
      bupivacaine (+/-ketorolac) versus normal saline or no irrigation for pain control
      after breast augmentation. The primary outcome was postoperative pain measured by
      visual analog scale. The study protocol was established a priori according to the
      recommendations of the Cochrane Collaboration. A bibliographical search was
      conducted in September 2015 in the following Cochrane Library databases: CENTRAL,
      MEDLINE, EMBASE, and Scielo. The strategy used for the search was ((augmentation
      AND ("mammoplasty"[MeSH Terms] OR "mammoplasty")) OR (("breast"[MeSH Terms] OR
      "breast") AND augmentation)) AND (("pain, postoperative"[MeSH Terms])). RESULTS:
      Four RCTs with a total of 264 participants were included. Two trials compared
      bupivacaine alone versus placebo (normal saline or no irrigation) and 3 trials
      compared bupivacaine plus ketorolac versus placebo. The combined irrigation of
      bupivacaine and ketorolac showed a clinically significant reduction of pain in
      the first postoperative hour and on postoperative day 5. The irrigation with
      bupivacaine compared with placebo significantly reduced pain assessed on
      postoperative day 4. CONCLUSION: The irrigation of bupivacaine with or without
      ketorolac was associated with a reduction of postoperative pain compared with
      control groups for the first 5 postoperative days. Due to the few number of
      trials included, these results should be correlated further clinically.

PMID- 29026811
TI  - The Use of Platelet-Rich Plasma for Storage of Surplus Harvested Skin Grafts.
AB  - BACKGROUND: There is a need for improved methods and storage media to sustain the
      tissue viability of autologous skin grafts. OBJECTIVE: To compare histological
      changes in human skin grafts stored in platelet-rich plasma (PRP) with those of
      grafts stored in saline. METHODS: Eight circular, 3-mm full-thickness skin graft
      samples were harvested from the abdominal skin of each of 5 patients scheduled to
      undergo an abdominoplasty procedure. Four of these graft samples were stored in
      saline, and the other 4 were stored in saline mixed with PRP prepared from the
      patient's own venous blood. Histological assessment of the microscopic appearance
      of the samples was performed on days 5, 8, 11, and 14. The integrity of the
      epidermal-dermal junction, number of keratinocytes with perinuclear halos,
      collagen organization, and number of fibroblasts per field were assessed. The
      cellular apoptosis rate was also measured on these same days. RESULTS: On day 5,
      significant differences were observed microscopically between the PRP- and saline
      stored grafts (P < .05). The grafts preserved in saline exhibited early marked
      cellular and nuclear swelling with pleomorphism, as well as early nuclear halo
      formation. The cell viability rate of the PRP group was significantly higher than
      that of the saline-stored group on day 8 (P < .05). CONCLUSION: Platelet-rich
      plasma and its inherent growth factors supported longer graft survival; however,
      its effect lasted only until day 8. Platelet-rich plasma may be beneficial if
      grafts need to be stored for delayed application(s).

PMID- 29026812
TI  - Medical Student Perception of Plastic Surgery and the Impact of Mainstream Media.
AB  - BACKGROUND: Plastic surgery as a discipline is poorly understood by many,
      including primary care physicians, nurses, medical students, and the public.
      These misconceptions affect the specialty in a number of ways, including referral
      patterns and recruitment of medical students into residency programs. The reason
      for these commonly held misconceptions has not yet been addressed in the plastic
      surgery literature. As such, we assessed medical students' knowledge and
      perceptions of plastic surgery as a discipline and explored factors influencing
      these opinions. METHODS: To assess medical students' knowledge and perceptions of
      plastic surgery, we conducted an online survey. A total of 231 medical students
      responded. Interviews were then conducted with 2 focus groups, in which we
      explored the survey results and reasons behind these misconceptions. RESULTS: As
      with previous studies, medical students showed a gap in knowledge with respect to
      plastic surgery. Although they were generally aware that plastic surgeons perform
      cosmetic procedures and treat burns, they were largely unaware that plastic
      surgeons perform hand and craniofacial surgeries. Focus groups revealed that
      television plays a large role in shaping their ideas of plastic surgery.
      CONCLUSION: Medical students have a skewed perception of the discipline of
      plastic surgery, and this is largely influenced by television. Interventions
      aimed at educating medical students on the matter are recommended, including a
      greater presence in the preclerkship medical school curriculum.

PMID- 29026813
TI  - Immediate Nerve Transfer for the Treatment of Peroneal Nerve Palsy Secondary to
      an Intraneural Ganglion: Case Report and Review.
AB  - Intraneural ganglion cysts that occur within the common peroneal nerve are a rare
      cause of foot drop. The current standard of treatment for intraneural ganglion
      cysts involving the common peroneal nerve involves (1) cyst decompression and (2)
      ligation of the articular nerve branch to prevent recurrence. Nerve transfers are
      a time-dependent strategy for recovering ankle dorsiflexion in cases of high
      peroneal nerve palsy; however, this modality has not been performed for
      intraneural ganglion cysts involving the common peroneal nerve. We present a case
      of common peroneal nerve palsy secondary to an intraneural ganglion cyst
      occurring in a 74-year-old female. The patient presents with a 5-month history of
      pain in the right common peroneal nerve distribution and foot drop. The patient
      underwent simultaneous cyst decompression, articular nerve branch ligation, and
      nerve transfer of the motor branch to the flexor hallucis longus to a motor
      branch of the anterior tibialis muscle. At final follow-up, the patient
      demonstrated complete (M4+) return of ankle dorsiflexion, no pain, and no
      evidence of recurrence and was able to weight bare without the need of orthotic
      support. Given the minimal donor site morbidity and recovery of ankle
      dorsiflexion, this report underscores the importance of considering early nerve
      transfers in cases of high peroneal neuropathy due to an intraneural ganglion
      cyst.

PMID- 29026814
TI  - Oral Examination.

PMID- 29026815
TI  - The Midas Touch: Gold and Its Role in the Global Economy.

PMID- 29026817
TI  - Comparing the Use of 3D Photogrammetry and Computed Tomography in Assessing the
      Severity of Single-Suture Nonsyndromic Craniosynostosis.
AB  - PURPOSE: Single-suture nonsyndromic craniosynostosis is diagnosed using clinical
      assessment and computed tomography (CT). With increasing awareness of the
      associated risks of radiation exposure, the use of CT is particularly concerning
      in patients with craniosynostosis since they are exposed at a younger age and
      more frequently than the average child. Three-dimensional (3D) photogrammetry is
      advantageous-it involves no radiation, is conveniently obtainable within clinic,
      and does not require general anaesthesia. This study aims to assess how 3D
      photogrammetry compares to CT in the assessment of craniosynostosis severity, to
      quantify surgical outcomes, and analyze the validity of 3D photogrammetry in
      craniosynostosis. METHODS: Computed tomography images and 3D photographs of
      patients who underwent craniosynostosis surgery were assessed and aligned to best
      fit. The intervening area between the CT and 3D photogrammetry curves at the
      supraorbital bar (bandeau) level in axial view was calculated. Statistical
      analysis was performed using Student t test. Ninety-five percent confidence
      intervals were determined and equivalence margins were applied. RESULTS: In
      total, 41 pairs of CTs and 3D photographs were analyzed. The 95% confidence
      interval was 198.16 to 264.18 mm2 and the mean was 231.17 mm2. When comparisons
      were made in the same bandeau region omitting the temporalis muscle, the 95%
      confidence interval was 108.94 to 147.38 mm2, and the mean was 128.16 mm2.
      Although statistically significant difference between the modalities was found,
      they can be attributable to the dampening effect of soft tissue. CONCLUSION:
      Within certain error margins, 3D photogrammetry is comparable to CT in assessing
      the severity of single-suture nonsyndromic craniosynostosis. However, a dampening
      effect can be attributable to the soft tissue. Three-dimensional photogrammetry
      may be more applicable for severe cases of craniosynostosis but not milder
      deformity. It may also be beneficial for assessing the overall appearance and
      aesthetics but not for determining underlying bony severity.

PMID- 29026816
TI  - Aesthetic Refinements in Forehead Flap Reconstruction of the Asian Nose.
AB  - BACKGROUND: Traditional paramedian forehead flap reconstruction exploits the
      aesthetic subunit principle. Refinements and outcomes of forehead flap nasal
      reconstruction largely reflect Western experience. Differences in ethnic Asian
      anatomy and wound healing may foster suboptimal outcomes. We modified methods to
      address Asian features by extending subunit and flap boundaries, minimizing flap
      thinning, and overbuilding the nasal framework to combat contraction and
      suboptimal scarring. METHODS: Between November 2010 and September 2015, 40 Asians
      were treated for nasal reconstruction with a modified forehead flap technique.
      Average age of 26 men and 14 women was 50.2 years (range: 10-87 years).
      Oncologic, traumatic, congenital, and infectious defects involving 1 (37%) or
      more (63%) subunits were reconstructed. Modifications to the classic forehead
      flap were extension of involved subunits and flap, conservative flap thinning,
      and framework overbuilding. RESULTS: Patients were followed for 20 months (range:
      16 months to 4 years 8 months). Nasal lining was reconstructed with hinge-over
      lining flaps, forehead flaps, free flaps, or regional flaps. Cartilage was
      reconstructed in 44 (88%) patients with autologous septum or ear in 33 (75%)
      cases. Costal cartilage was needed in 11 (25%) cases. In 48 (96%) cases, the
      ipsilateral forehead was used. There were 5 (10%) wound infections, 2 (4%)
      dehisced wounds, and 2 (4%) occurrences of distal flap necrosis. Nasal aesthetic
      results were 72.6% good, 23.3% fair, and 4% poor. Donor site aesthetic results
      were 74% good and 26% fair. Three case reports are included. CONCLUSION: We
      report favourable results of forehead flap nasal reconstruction using refinements
      tailored to ethnic Asians.

PMID- 29026819
TI  - The Role of Dynamic Ultrasound in the Immediate Conservative Treatment of Volar
      Plate Injuries of the PIP Joint: A Series of 78 Patients.
AB  - INTRODUCTION: The management of volar plate avulsion fractures in the context of
      a stable joint and a bony fragment of less than 30% has traditionally been
      conservative. This study was performed to assess volar plate healing with high
      resolution ultrasound in order to provide early full mobilization. MATERIAL AND
      METHODS: Between January 2012 and December 2013, 78 patients with volar plate
      injuries of the proximal interphalangeal (PIP) joints (42 distortions and 36
      dislocations) were treated conservatively in our department for volar plate
      avulsion fracture associated with stable joint and bony fragment inferior to 30%
      of the intra-articular surface assessed both by radiography and ultrasound.
      Conservative treatment included extension stop splinting for the first 2 weeks
      and Coban bandage until 6 weeks postinjury. However, it may be possible to modify
      the duration of extension stop splinting based on clinical and ultrasound
      findings (with no additional X-ray) performed every 2 weeks for the first 3
      months and then at 4 months postinjury. Only patients with residual contracture
      at the 4-month assessment had prolonged follow-up in order to ensure adequate
      dynamic splint therapy. RESULTS: The amount of soft tissue oedema and the
      mobility of the volar plate were factors used to determine return to full
      mobilization. Mean extension-stop-splint wear was 16 +/- 2 days. During the first
      2 follow-up assessments, 4 patients were excluded from the study because of the
      instability of the PIP joint. One patient required refixation of a large fragment
      of 30%, 2 patients required superficial flexor tendon (FDS) tenodesis of the
      unstable volar plate in hyperextension and 1 other patient required arthrodesis
      of the PIP joint. In 51 patients, the postoperative follow-up was free of
      complications at 4 months. In 18 patients, flexion contracture of 20 degrees 
      (range 11 degrees -40 degrees ) and oedema during follow-up required dynamic
      extension splints for 3 to 5 months. After this time, 5 patients had a residual
      contracture of 10 degrees  to 15 degrees . CONCLUSION: Avulsion fractures of the
      volar plate at the PIP joint are common. In general, they have a good outcome
      using the conservative treatment with extension block splints. Flexion
      contracture is a common complication and may be reduced by immediate splints in
      full extension at night and Coban bandage during the day. High-resolution
      sonography is a convenient tool to evaluate palmar plate stability, to assess
      reduction of oedema, and thus to guide safe return to full range of movement.

PMID- 29026818
TI  - Variations in the Anatomical Structures of the Guyon Canal.
AB  - BACKGROUND: Compression neuropathy of the ulnar nerve at the Guyon canal is
      commonly seen by hand surgeons. Different anatomical variations of structures
      related to the Guyon canal have been reported in the literature. A thorough
      knowledge of the normal contents and possible variations is essential during
      surgery and exploration. OBJECTIVES: To review the recognized anatomical
      variations within and around the Guyon canal. METHODS: This study is a narrative
      review in which relevant papers, clinical studies, and anatomical studies were
      selected by searching electronic databases (PubMed and EMBASE). Extensive manual
      review of references of the included studies was performed. We also describe a
      case report of an aberrant muscle crossing the Guyon canal. RESULTS: This study
      identified several variations in the anatomical structures of the Guyon canal
      reported in the literature. Variations of the ulnar nerve involved its course,
      branching pattern, deep motor branch, superficial sensory branch, dorsal
      cutaneous branch, and the communication with the median nerve. Ulnar artery
      variations involved its course, branching pattern, the superficial ulnar artery,
      and the dorsal perforating artery. Aberrant muscles crossing the Guyon canal were
      found to originate from the antebrachial fascia, pisiform bone, flexor
      retinaculum, the tendon of palmaris longus, flexor carpi ulnaris, or flexor carpi
      radialis; these muscles usually fuse with the hypothenar group. CONCLUSION: The
      diverse variations of the contents of the Guyon canal were adequately described
      in the literature. Taking these variations into consideration is important in
      preventing clinical misinterpretation and avoiding potential surgical
      complications.

PMID- 29026820
TI  - A Qualitative Assessment of the Journey to Delayed Breast Reconstruction.
AB  - BACKGROUND: Canada has low immediate breast reconstruction (IBR) rates compared
      to the United States and Europe. Breast cancer survivors live with mastectomy
      defects sometimes for years, and this represents an area for improvement in
      cancer care. PURPOSE: This study qualitatively assessed (1) information provided
      about breast reconstruction at the time of cancer diagnosis among women seeking
      delayed breast reconstruction (DBR) and (2) referral practices for plastic
      surgery consultation for DBR. METHODS: Fifty-two consecutive patients seen in
      consultation for DBR at a single Canadian tertiary care centre completed
      questionnaires regarding their experience in seeking breast reconstruction. Seven
      semi-structured interviews were conducted to further explore themes identified
      through questionnaires. Questionnaire responses and interview transcripts were
      analyzed for recurring themes using standard qualitative techniques. RESULTS: A
      significant portion of women (43%) was interested in reconstruction prior to
      mastectomy, yet IBR was infrequently discussed (14%) or discouraged by their
      oncologic surgeons (33%). Common patient reasons for not pursuing IBR were
      referring physician objection and not having adequate knowledge. Women expressed
      wanting to discuss reconstruction at the time of cancer diagnosis. Half of the
      patients had attended another consultation, but the initial plastic surgeon
      either did not offer procedures for which these women were candidates or had
      prohibitively long surgical wait times. CONCLUSION: Lack of information about
      reconstructive options at the time of cancer diagnosis and perceived access
      barriers to plastic surgeons may contribute to underutilization of IBR in Canada.
      Access to breast reconstruction can be improved by reducing inefficiencies in
      plastic surgery referrals.

PMID- 29026821
TI  - Comparison of Resorbable Mesh (Poly L-Lactide/Glycolic Acid) and Porous
      Polyethylene in Orbital Floor Fractures in an Experimental Model.
AB  - BACKGROUND: Resorbable mesh and porous polyethylene are frequently used
      alloplastic materials for the treatment of the orbital blowout fractures. The
      literature lacks reports comparing their long-term effects on experimental
      models. OBJECTIVE: Our aim was to radiologically and histologically evaluate the
      effectiveness and safety of porous polyethylene and resorbable mesh in a rabbit
      orbital blowout fracture model. METHODS: Twelve New Zealand white rabbits (24
      orbits) were randomized to 4 groups. In group 1, only orbital floor dissection
      was done. In group 2, following orbital floor dissection, a 10-mm defect was
      created without any extra procedure. In group 3, following a 10-mm defect
      creation, a 12-mm-round cut porous polyethylene was placed on the defect. In
      group 4, following a 10-mm defect creation, a 12-mm-round cut resorbable mesh was
      placed on the defect. Computed tomographic analysis was performed during follow
      up period. Orbital floors were evaluated histologically at month 6. RESULTS: No
      clinical complications were observed during follow-up period. In radiological
      evaluation, there was no statistically significant difference between groups
      regarding bone formation. In histological evaluation, the connective tissue was
      denser, and organized and better bone formation was observed in group 3 and 4
      when compared with other groups. CONCLUSION: Although no significant radiological
      changes were present, porous polyethylene and resorbable mesh performed better
      histologically. They were effective and well tolerated for reconstruction of the
      isolated orbital floor defects.

PMID- 29026822
TI  - Intraoperative Nerve Stimulation During Brachial Plexus Surgery: Comparison
      Between a Totally Disposable Nerve Stimulator and Nerve Stimulator Normally Used
      for Nerve Blocks.
AB  - BACKGROUND: Intraoperative nerve stimulation is done routinely in brachial plexus
      and peripheral nerve surgery as well as in selective neurectomy in spastic
      patients. OBJECTIVE: The current study compares the use of 2 different devices
      for nerve stimulation: a totally disposable nerve stimulator and a nerve
      stimulator used for nerve blocks by anesthetists. METHODS: A retrospective study
      of 60 patients who underwent brachial plexus surgery: In 30 patients, we used the
      totally disposable nerve stimulator (group 1) and in another 30 patients, we used
      the anesthesia device (group 2). The cost of disposable materials used for nerve
      stimulation was calculated in each group. The same surgeon performed all
      operations, and he was asked to give his subjective opinion regarding the
      convenience and ease of use of the device in each group. RESULTS: The main
      advantages of the totally disposable device are its placement totally within the
      sterile field, and it is operated by the surgeon without the need to communicate
      with the anesthetist. However, the totally disposable device had several major
      disadvantages when compared to the anesthesia device. Firstly, the disposable
      stimulator can only deliver 0.5, 1.0, and 2.0 mA stimuli, while the anesthesia
      device can deliver stimuli of 0.1 to 5 mA (in 0.1 mA increments). Secondly, the
      disposable stimulator frequently fails to operate during surgery, and this is not
      experienced with the anesthesia device. Finally, the cost of disposables is less
      using the anesthesia device. CONCLUSION: Our center has stopped using the
      disposable nerve stimulator in favour for the anesthesia device.

PMID- 29026823
TI  - Ivy Loop Wiring: A Useful Form of Endotracheal Tube Stabilization in Burn
      Patients.
AB  - The stabilization of endotracheal tubes in the burn population presents many
      problems. Access to the face for dressings, debridements, and the use of topical
      antimicrobials prevent adequate stabilization of the endotracheal tube with
      commonly used methods. Conventional methods have an increased risk of shifting,
      which can lead to injury to the friable burned tissue or unplanned extubation. To
      prevent these complications, alternative methods using the dentition to stabilize
      the endotracheal tube have been described. Here, we present our technique of
      using Ivy loops to secure the endotracheal tube. It is a simple method with low
      complications that provides a strong stabilization of the tube while giving
      access to the face.

PMID- 29026824
TI  - Textured Breast Implants: A Closer Look at the Surface Debris Under the
      Microscope.
AB  - BACKGROUND: Texturing of breast implants is done to decrease the risk of
      associated complications. Each manufacturer utilizes unique and at times
      proprietary techniques to texture the surface of their implants. Little is known
      about the integrity of this surface structure texturing or the propensity for the
      surfaces to shed particulate matter. This study aimed to determine the extent of
      surface particulate shedding from 3 textured implants approved by the US Food and
      Drug Administration (FDA), which are manufactured by Allergan, Mentor, and
      Sientra. METHODS: Control images of each of the 3 textured breast implants were
      obtained with scanning electron microscopy (SEM). A liquid adhesive, ethylene
      vinyl acetate (EVA) copolymer was then applied to the external shell of the
      implants, allowed to cool, and peeled from the surface. Images of the EVA
      copolymer were taken with SEM to qualitatively analyze displacement of surface
      particulate debris. Scanning electron microscopy imaging of the implants was
      repeated for qualitative comparisons with the control images. RESULTS: The peeled
      copolymer of the 3 implants exhibited surface shedding. Comparison of the 3
      breast implants showed the shedding to be greatest for the Allergan implant.
      CONCLUSIONS: This study highlights the dynamic surface material properties of the
      3 FDA-approved breast implants. Shedding of particulate matter from the implant
      surfaces can be precipitated by moderate adhesion. Our qualitative examination of
      SEM findings showed more debris shed from the Allergan breast implants than from
      the Mentor or Sientra implants.

PMID- 29026825
TI  - The Keystone Flap-A Case Series Demonstrating Practical Design, Use, and
      Applications.
AB  - INTRODUCTION: The keystone design perforator island flap is a trapezoidal-shaped
      random perforator island flap with many advantages over primary closure, skin
      grafting, and other local flaps for soft tissue reconstruction commonly
      encountered with cancer excisions. METHODS: This case series of 39 keystone flaps
      in 37 patients reviews the practical design, use, and applications of the flap
      while highlighting certain important considerations. Keystone flaps were designed
      as in the original description, with a minor modification in the lower extremity
      where a higher flap to defect width ratio was used. RESULTS: Defects varying in
      size from 6 to 63 cm2 were reconstructed in 23 males and 14 females ranging in
      age from 49 to 89. In all 39 cases, there were 2 minor complications of partial
      flap dehiscence and no major complications such as partial or complete flap loss.
      CONCLUSION: The keystone flap is a versatile and reliable flap with applications
      almost anywhere on the body. A higher ratio of flap width to defect width up to
      1:3 is more appropriate for the lower extremity where tension is higher.

PMID- 29026826
TI  - The Superficial Femoral Artery Flap: A 3-Dimensional Anatomical Study.
AB  - BACKGROUND: The superficial femoral artery perforator (SFAP) flap offers
      advantages for pedicled transfer including consistent perforators and vascular
      territory, well-hidden donor site scar, and hairless flap skin. This article
      provides a historical overview of the SFAP flap and describes the vascular
      anatomy of the SFAP by 3-dimensional analysis and angiography. METHODS: Ten fresh
      cadavers were injected using the lead oxide technique through the femoral artery.
      Spiral computed tomographic scanning and 3-dimensional evaluation were used to
      describe the SFAP number, diameter, length, type, and location. RESULTS: A total
      of 288 perforators in 15 cadaver limbs were identified; 19 +/- 8 perforators per
      thigh >=0.5 mm in diameter, with an average diameter of 0.8 +/- 0.3 mm and a
      range of 0.5 to 2.1 mm; the mean length of each perforator was 68 +/- 31 mm; 45%
      were septocutaneous and 55% were musculocutaneous. The medial thigh region was
      divided into 6 areas (anterior and posterior halves, then the proximal third,
      middle third, and distal third of each). The majority of the perforators were
      located in the middle and distal thirds of the anteromedial thigh (33% each).
      CONCLUSIONS: Using 3-dimensional vascular anatomical analysis, the number,
      location, length, type, and diameter of the SFAP were documented. In the
      literature, relatively few reports of the use of the SFAP flap are available,
      however, this is a valid donor site with consistent cutaneous perforators
      suitable for harvest as a local or regional flap transfer. This is the first 3
      dimensional vascular anatomical study to comprehensively document the vascular
      anatomy of the SFAP flap.

PMID- 29026827
TI  - Evaluation of Secondary and Late Secondary Alveolar Bone Grafting on 66
      Unilateral Cleft Lip and Palate Patients.
AB  - OBJECTIVE: The aim of this retrospective study was to evaluate the outcomes of
      secondary alveolar bone grafting and late secondary alveolar bone grafting in 66
      unilateral cleft lip and palate patients. MATERIALS AND METHODS: The total
      patients were 66 unilateral cleft lip and palate patients, out of which 19
      patients underwent secondary alveolar bone grafting and 47 patients underwent
      late secondary alveolar bone grafting. Autogenous anterior iliac crest cancellous
      bone graft was harvested and used for grafting the alveolar clefts. Radiographic
      assessment based on Enemark's scoring according to the marginal bone levels was
      done on the intraoral periapical radiographs taken 6 months after performing the
      surgery. RESULTS: Twelve (63%) out of the 19 patients on whom secondary alveolar
      bone grafting was done achieved score 1 (optimal marginal bone levels), whereas
      only 12 (25%) out of the 47 patients achieved score 1 amongst the late secondary
      alveolar bone graftings. Overall results showed, probability, P = .034
      (statistically significant). CONCLUSION: This study reaffirmed the fact that
      alveolar bone grafting when done in preadolescent age group (secondary alveolar
      bone grafting) gives better results in terms of marginal bony consolidation and
      maintaining the continuity of the alveolar arch, but the late presentation (late
      secondary alveolar bone grafting) should not be the refusal criteria for
      performing the alveolar bone grafting. Although the latter patients may not be
      rewarded in terms of bony consolidation as much as the preadolescent patients the
      potential of successful surgery in them still exists in terms of providing a
      platform for the dental implant placement, improvement in the soft tissue
      symmetry and aesthetics of the face.

PMID- 29026828
TI  - Objective Outcomes of Minimally Invasive Temporalis Tendon Transfer for Prolonged
      Complete Facial Paralysis.
AB  - OBJECTIVES: We describe an approach to reanimation of complete, prolonged facial
      paralysis using minimally invasive temporalis tendon transfer (MIT3) by the
      melolabial or transoral approach. Objective outcome measures are evaluated based
      on symmetry, and grading of preoperative/post-operative results and the scar at
      the melolabial fold. STUDY DESIGN: Retrospective cohort study. METHODS: Twenty
      five patients undergoing the MIT3 technique were studied. Photographic analysis
      was used to determine the percentage of difference between the 2 sides
      (symmetry). Using the Delphi method to achieve consensus, a panel of experts
      graded pre/post-operative photos using the Terzis' Facial Grading System and a 1
      to 10 Likert-type scale and the melolabial scar using the Beausang Scar Scale.
      RESULTS: Percentage of difference (symmetry) with smiling improved from 18.6% +/-
      1.5% (mean +/- standard error of the mean [SEM]) preoperatively to 5.0 +/- 0.9%
      (mean +/- SEM) post-operatively. Expert grading by the Terzis system showed
      improvement post-operatively (mean 3.7/5; median 3.6/5) versus preoperatively
      (mean 1.5/5; median 1.2/5). Perceived improvement was also largely favourable
      (mean 8.1/10; median 8.0/10). Melolabial scar grading was favourable in terms of
      colour (mean 1.53/4), surface character (mean 1.05/2), contour (mean 1.60/4), and
      distortion (mean 1.74/4). CONCLUSIONS: The MIT3 technique offers immediate,
      predictable, and symmetrical return of smile function. Objective symmetry
      analysis and favourable expert grading of both pre-/post-operative photographs
      and the scar at the melolabial fold demonstrate applicability for facial
      reanimation in patients where other procedures have failed, or when a direct
      return to function is desired. Both the melolabial approach and transoral
      approach were found to be acceptable and effective, although applicability
      varies.

PMID- 29026829
TI  - Aggressive Combined Medical and Surgical Management of Mucormycosis Results in
      Disease Eradication in 2 Pediatric Patients.
AB  - Rhinocerebral mucormycosis is an acute, rapidly fatal, fungal infection,
      classically involving the nasal mucosa and paranasal sinuses. It is an
      aggressive, opportunistic infection that frequently progresses to involve the
      orbit and cerebrum. Cerebral extension in immunocompromised patients is almost
      universally fatal. There are limited data on mucormycosis in pediatric
      immunocompromised patients in the literature, with only few reports on
      rhinocerebral involvement. The immunocompromised patients described in this
      report presented with suspected periorbital and nasal cellulitis, progressing
      rapidly to necrotic changes in nasal tissue and oral palatal mucosa. In these
      patients, the surgical resection of mucormycosis-infected tissue followed by flap
      reconstruction combined with medical treatment effectively treated the infection,
      allowed for the rapid resumption of chemotherapy and dramatically improved the
      quality of life for both the patient and their family.

PMID- 29026830
TI  - Treatment of Constriction Bands of Limbs by Fat Injection: An Additional
      Modality.
AB  - BACKGROUND: Constriction bands in the majority of cases presents as a contour
      deformity. The gold standard of treatment is a single-stage constriction ring
      excision and serial Z-plasty. The expense is unsightly scarring. We present case
      reports of deformity correction by serial fat injections. METHODS AND
      PARTICIPANTS: Three case studies of children in whom this modality was used in
      limbs to correct the deformity are presented. RESULTS: Two participants showed a
      good correction of the deformity and in a single-case treatment failed requiring
      excision and serial Z-plasty for correction. CONCLUSION: Fat injection in
      combination with Khouri's technique of aponeurotomies is an attractive modality
      of managing superficial constriction bands of limbs.

PMID- 29026831
TI  - Oral Examination.

PMID- 29026832
TI  - I'm a Plastic Surgeon: How Should I Manage My Debt?

PMID- 29026834
TI  - Conservative approach to the acute management of a large mesenteric cyst.
AB  - Mesenteric cysts are rare, benign gastrointestinal cystic lesions, which are
      often non-troublesome and present as an incidental radiological finding. However,
      surgery is often performed in the acute setting to remove lesions that are
      symptomatic. This report highlights the case of a large, symptomatic mesenteric
      cyst managed successfully with initial conservative measures followed by planned
      elective surgery. A 44-year-old female presented with a four-day history of
      generalised abdominal pain associated with distension, fever, diarrhoea and
      vomiting. Computer tomography revealed a large (21.7 cm * 11.8 cm * 14 cm)
      mesenteric cyst within the left abdomen cavity. She was admitted and treated
      conservatively with intravenous fluids and antibiotics for four days, which lead
      to complete symptom resolution. Follow-up at intervals of one and three months
      revealed no return of symptoms. An elective laparotomy and excision of the
      mesenteric cyst was then scheduled and performed safely at nine months after the
      initial presentation. Compared to acute surgery, acute conservative management
      followed by planned elective resection of a symptomatic mesenteric cyst may prove
      safer. The withholding of an immediate operation may potentially avoid
      unnecessary operative risk and should be considered in patients without
      obstructive and peritonitic symptoms. Our case demonstrated the safe use of
      initial conservative management followed by planned elective surgery of a
      mesenteric cyst found in the acute setting, which was symptomatic but was not
      obstructive or causing peritonitic symptoms.

PMID- 29026835
TI  - Recurrent aneurysmal bone cyst of talus resulted in tibiotalocalcaneal
      arthrodesis.
AB  - Aneurysmal bone cyst (ABC), a locally benign aggressive lytic lesion of either
      primary or secondary origin, seldom involves the talus. Herein, we present a 25
      year-old man with recurrent ABC of the talus after curettage and bone grafting,
      which was managed by total resection followed by filling the defect using fibular
      graft and finally tibiotalocalcaneal arthrodesis due to articular surface
      involvement. At 18 mo postoperatively, no recurrence was detected. Arthrodesis
      might be a good option in cases with recurrent ABC of the talus especially with
      articular surface involvement.

PMID- 29026836
TI  - Anti-N-methyl-D-aspartate receptor encephalitis that aggravates after
      acinetobacter baumannii pneumonia: A case report.
AB  - We report an atypical case of anti-N-methyl-D-aspartate receptor encephalitis
      (ANMDARE). A 27-year-old man diagnosed with ANMDARE received immunotherapy and
      had a good recovery. However, within one month, he developed severe status
      epilepticus and decreased level of conscience with new hyperpyrexia and dyspnea,
      and was admitted to the emergency intensive care unit. Acinetobacter baumanii
      were found in the sputum culture; and anti-NMDAR antibodies were positive (titer:
      1/80) in the cerebrospinal fluid. Repeated immunotherapy was administered with
      antibacterial agents, and the patient recovered except for mild psychiatric
      sequelae. This is the first report of ANMDARE that aggravates after acinetobacter
      baumannii pneumonia. Awareness and knowledge of this disorder should be extended,
      especially in the emergency medicine community.

PMID- 29026833
TI  - Primary prevention of cardiovascular disease in older adults in China.
AB  - Over the past two decades, the percentage of Chinese who is 60 years or older has
      increased from 5.2% in 1995 to 10.5% in 2015. Approximately 16% of the population
      in China was 60 years old and above in 2015. Since 1990, cardiovascular disease
      (CVD) has been the leading cause of death in China. Cardiovascular medications of
      older adults are usually more complicated than younger age groups due to
      polypharmacy, the presence of comorbidities and more susceptible to treatment
      related adverse outcomes. Therefore, effective primary prevention of CVD for
      older adults is important in sustaining the health of older adults and reducing
      the burden of the healthcare system. Proper management of CVD-related risk
      factors, such as hypertension, dyslipidemia, diabetes and obesity, can remarkably
      reduce risks of CVDs in older Chinese. These risk factors can be modified by
      managing blood pressure, glucose and lipids via lifestyle modifications or
      receiving medications. Smoking cessation, healthy diets, strict alcohol intake
      and moderate physical exercise are examples of recommended lifestyle changes for
      remarkably recovering health conditions of older adults who have hypertension,
      dyslipidemia, obesity, diabetes or complications. Treatment prescriptions of
      older adults, in general, are recommended to be individualized and to be
      initiated at a low dose. The future directions for better primary CVD prevention
      in older adults include establishing guidelines for primary prevention of CVD for
      different older adults and further research on better management strategies of
      CVD risks for elderly Chinese.

PMID- 29026838
TI  - Tumor Necrosis Factor-alpha Antibodies in Fistulizing Crohn's Disease: An Updated
      Systematic Review and Meta-analysis.
AB  - Medical treatment for fistulizing Crohn's disease (FCD) is changing rapidly over
      the time by the introduction of novel therapeutic medicines, while no global
      consensus is available. This study aims to accomplish a systematic review and
      meta-analysis on the efficacy of tumor necrosis factor-alpha antibodies (anti-TNF
      alpha antibodies) versus placebo in FCD. A systematic review of published
      literature was carried out till December 2016, and a meta-analysis of identified
      studies was done. Data have been explored from PubMed, Scopus, Cochrane Library
      Database, and Web of Science. Predefined exclusion criteria for included studies
      in meta-analysis are based on search methodology and are as follows: Randomized
      clinical trial about Crohn's disease (CD) patients without fistula, pediatrics
      CD, randomized clinical trials about pregnant women with FCD, nonhuman studies,
      randomized clinical trials with surgical therapies interventions, conference
      abstracts, case reports, and language other than English studies. All randomized
      placebo-controlled trials were included. To assess risk of bias, Jadad score was
      applied to evaluate trials' methodological quality. Relative risk (RR) and 95%
      confidence intervals were computed using Mantel-Haenszel and/or Rothman-Boice
      (for fixed effects) or Der Simonian-Laird (for random effects) techniques. Nine
      studies attained defined inclusion criteria. The meta-analysis results showed
      that anti-TNF-alpha antibodies are remarkably more effective in comparison to
      placebo for fistula closure maintenance (RR = 2.36; 95% confidence interval: 1.58
      3.55; P < 0.0001) in patients with FCD, whereas anti-TNF-alpha antibodies were
      not superior to placebo neither in fistula improvement nor in fistula closure. We
      concluded that adalimumab and certolizumab pegol are both effective in fistula
      closure maintenance in adult patients with FCD.

PMID- 29026839
TI  - Missing the Benefit of Metformin in Acute Myeloid Leukemia: A Problem of
      Contrast?
AB  - OBJECTIVE: To evaluate whether metformin's cancer-related benefits reported in
      patients with solid tumors (ST) are also present in acute myeloid leukemia (AML)
      patients. METHODS: Baseline demographic and clinical history for all diabetes
      mellitus patients newly diagnosed with AML or cancer of the breast, ovary,
      prostate, gastrointestinal tract, lung, or kidney at Roswell Park Cancer
      Institute in Buffalo, NY (January 2003-December 2010, n = 924) was collected.
      Overall survival (OS) and disease-free survival (DFS) were assessed by Kaplan
      Meier (KM) analysis and Cox proportional hazards regression (hazard ratio [HR]).
      FINDINGS: Baseline metformin use provided significant OS and DFS benefit in ST
      but not in AML (KM: PST-OS= 0.003; PST-DFS= 0.002; PAML-OS= 0.961; PAML-DFS=
      0.943). AML median survival was slightly better with metformin use, but users
      derived no relapse benefit. In ST, metformin nonusers had shorter median
      survival, 57.7 versus 86 months, and poorer outcomes (HRST-OS= 1.33; PST-OS=
      0.002; HRST-DFS= 1.32; PST-DFS= 0.002). These findings remained significant in
      age-adjusted models (HRST-OS= 1.21; PST-OS= 0.039; HRST-DFS= 1.23; PST-DFS= 0.02)
      but not fully adjusted models (HRST-OS= 0.96; PST-OS= 0.688; HRST-DFS= 1.0; PST
      DFS= 0.94). Higher mortality was noted in AML patients taking insulin versus oral
      diabetes pharmacotherapy at baseline (HRAML-OS= 2.03; PAML-OS= 0.04). CONCLUSION:
      Lack of metformin benefit in AML could be due to advanced age at cancer
      diagnosis. Metformin substitution with insulin before computed tomography scans
      with contrast - a frequent AML assessment practice - may also explain the lack of
      subsequent benefit despite taking metformin at baseline. A temporary metformin
      substitution is recommended by the package insert due to a possible drug
      interaction with the contrast dye. Our data suggest that metformin substitution
      was permanent in many patients. Nonetheless, the observed benefit in other
      malignancies warrants further investigation of metformin use in AML.

PMID- 29026837
TI  - BINDING SITE ANALYSIS OF THE CAENORHABDITIS ELEGANS NR4A NUCLEAR RECEPTOR NHR-6
      DURING DEVELOPMENT.
AB  - Members of the NR4A subfamily of nuclear receptors make up a highly conserved,
      functionally diverse group of transcription factors implicated in a multitude of
      cellular processes such as proliferation, differentiation, apoptosis, metabolism
      and DNA repair. The gene nhr-6, which encodes the sole C. elegans NR4A nuclear
      receptor homolog, has a critical role in organogenesis and regulates the
      development of the spermatheca organ system. Our previous work revealed that nhr
      6 is required for spermatheca cell divisions in late L3 and early L4 and
      spermatheca cell differentiation during the mid L4 stage. Here, we utilized
      chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq)
      to identify NHR-6 binding sites during both the late L3/early L4 and mid L4
      developmental stages. Our results revealed 30,745 enriched binding sites for NHR
      6, ~70% of which were within 3 kb upstream of a gene transcription start site.
      Binding sites for a cohort of candidate target genes with probable functions in
      spermatheca organogenesis were validated through qPCR. Reproductive and
      spermatheca phenotypes were also evaluated for these genes following a loss-of
      function RNAi screen which revealed several genes with critical functions during
      spermatheca organogenesis. Our results uncovered a complex nuclear receptor
      regulatory network whereby NHR-6 regulates multiple cellular processes during
      spermatheca organogenesis.

PMID- 29026840
TI  - Impact of CYP2C19 Polymorphisms on Serum Concentration of Voriconazole in Iranian
      Hematological Patients.
AB  - OBJECTIVE: This study aimed to determine the portion of Iranian patients who
      attain therapeutic serum concentrations of voriconazole (VRCZ) following
      administration of fixed doses. In addition, the effect of CYP2C19 polymorphism on
      serum levels of VRCZ was also investigated. METHODS: Forty-eight adult patients
      of Iranian origin with hematologic malignancies, who received VRCZ for treatment
      of invasive aspergillosis, were recruited into the study. Blood samples were
      drawn at day 4 of treatment to measure trough drug concentrations and determine
      genotyping of CYP2C19 polymorphisms of each patient. High-performance liquid
      chromatography method was used for measuring VRCZ serum level and CYP2C19
      polymorphisms were conducted by Sanger sequencing. Demographic and clinical
      characteristics of patients alongside with CYP2C19 polymorphisms were assessed to
      determine the effective factor/s on VRCZ serum concentration. FINDINGS: Seventy
      three percent of patients achieved therapeutic serum concentrations of VRCZ with
      administration of usual fixed doses in clinical practice. There was no
      correlation between weight-adjusted dose and serum concentrations of VRCZ. Mean
      serum levels were significantly different neither in genders nor in routes of
      administrations. Extensive and ultrarapid metabolizers (URMs) comprised 48.7% and
      21.6% study population, respectively. CYP2C19 polymorphism dramatically
      influenced the trough levels of VRCZ, so that all patients with subtherapeutic
      levels expressed URM phenotype. CONCLUSION: With respect to high incidence of URM
      phenotype in Iranian population, and observed association of this phenotype with
      sub-therapeutic levels in our study, performing therapeutic drug monitoring is
      strongly recommended for all patients.

PMID- 29026841
TI  - Causes of Medication Errors in Intensive Care Units from the Perspective of
      Healthcare Professionals.
AB  - OBJECTIVE: This study was conducted to explore and to describe the causes of
      medication errors in Intensive Care Units (ICUs) from the perspective of
      physicians, nurses, and clinical pharmacists. METHODS: The study was conducted
      using a descriptive qualitative method in 2016. We included 16 ICUs of seven
      educational hospitals affiliated to Isfahan University of Medical Sciences.
      Participants included 19 members of the healthcare team (physician, nurse, and
      clinical pharmacist) with at least 1 year of work experience in the ICUs.
      Participants were selected using purposeful sampling method. Data were collected
      through semi-structured individual interviews and were used for qualitative
      content analysis. FINDINGS: The four main categories and ten subcategories were
      extracted from interviews. The four categories were as follows: "low attention of
      healthcare professionals to medication safety," "lack of professional
      communication and collaboration," "environmental determinants," and "management
      determinants." CONCLUSION: Incorrect prescribing of physicians, unsafe drug
      administration of nurses, the lack of pharmaceutical knowledge of the healthcare
      team, and the weak professional collaboration lead to medication errors. To
      improve patient safety in the ICUs, healthcare center managers need to promote
      interprofessional collaboration and participation of clinical pharmacists in the
      ICUs. Furthermore, interprofessional programs to prevent and reduce medication
      errors should be developed and implemented.

PMID- 29026842
TI  - Knowledge, Attitude and Practice of Iranian Pharmacists, Body Builders, and Their
      Coaches Regarding Sports Supplements.
AB  - OBJECTIVE: This study is conducted on Iranian pharmacists, coaches, and athletes
      regarding sports supplements to assess their knowledge, attitude, and practice
      (KAP) regarding sports supplements. METHODS: This was a cross-sectional study
      conducted in 2015. The study population consisted of all community pharmacists,
      bodybuilders, and bodybuilding coaches. The questionnaire was applied consisting
      some demographic questions and 25 questions for assessing KAP (6, 9, and 10,
      respectively). The collected data were analyzed with independent t-test, ANOVA,
      and Pearson correlation. FINDINGS: In all three studied groups, the mean of KAP
      was upper than intermediate level 3 (P < 0.05) except the pharmacists' knowledge.
      A statistically significant difference appears between knowledge and age of
      pharmacists (P = 0.007). In addition, there was a significant relationship
      between coaches' practice and age (P = 0.04). CONCLUSION: According to the
      results although the studied groups have the intermediate level of KAP, organized
      and regular education courses are highly recommended along with paying more
      attention to the curriculum taught in the pharmacy schools according to the
      community current needs.

PMID- 29026843
TI  - Melatonin Supplementation May Improve the Outcome of Patients with Hemorrhagic
      Stroke in the Intensive Care Unit.
AB  - OBJECTIVE: Although mechanical ventilation is frequently a life-saving therapy,
      its use can result in unwanted side effects. It has been well documented that the
      choice of sedating agent may influence the duration of mechanical ventilation.
      Melatonin is a sedative and analgesic agent without any respiratory depressant
      effect which makes it an attractive adjuvant for sedation in the intubated
      patients. The aim of this study is to evaluate the effect of melatonin on the
      duration of mechanical ventilation in patients with hemorrhagic stroke. METHODS:
      Forty adult intubated patients with hemorrhagic stroke, who were admitted to the
      Intensive Care Unit (ICU) within 24 h of onset, were enrolled in this randomized
      double-blind study. Subjects in the melatonin group received 30 mg of melatonin
      every night throughout the nasogastric tube. Length of ICU stay, mortality, and
      duration of mechanical ventilation were recorded for all patients. FINDINGS: The
      duration of mechanical ventilation and length of ICU stay were shorter in
      patients who received melatonin in comparison with the control group, and this
      difference was statistically significant for the length of ICU stay and
      marginally significant for the duration of mechanical ventilation. Although not
      statistically significant, the mortality rate of the control group was 30%,
      almost double that of the study group (15%). CONCLUSION: Melatonin possesses
      hypnotic, analgesic, anti-inflammatory, and anti-oxidative properties that
      distinguish it as an attractive adjuvant in patients under mechanical
      ventilation. In conclusion, the administration of melatonin may facilitate the
      weaning process through decreasing the consumption of sedatives with respiratory
      depressant properties as well as preventing ventilator-associated lung injury.

PMID- 29026844
TI  - An Interprofessional Collaboration between Medicine and Pharmacy Schools:
      Designing and Evaluating a Teaching Program on Practical Prescribing.
AB  - OBJECTIVE: Medical students need proper education in drug prescription. The aim
      of the present study is to introduce a course that improves the students'
      prescribing skills and also promotes an interprofessional collaboration between
      medicine and pharmacy schools. METHODS: This study was done in a skill laboratory
      at the pharmacotherapy department of Tehran University of Medical Sciences,
      Tehran, Iran. The course was an 18-h interactive workshop in 3 days under the
      supervision of clinical pharmacists. A total of 18 medical students participated
      in these classes before their internship. Before and after each class, they were
      given tests and paired t-test was done to compare the marks. FINDINGS: A total of
      18 medical students participated in this study. The results showed that the
      knowledge of the students on pharmacotherapy, drug information, and prescribing
      skills has been significantly improved at the end of the course. CONCLUSION:
      Using clinical pharmacists to the present pharmacotherapy course could be an
      effective model for medical students to obtain better prescribing skills.

PMID- 29026845
TI  - Osteonecrosis of the Jaws in Patient Received Bisphosphonates and Sunitinib
      Separately: A Case Report.
AB  - Recently published reports have suggested that antiangiogenic drugs such as
      sunitinib could potentiate the osteonecrosis of the jaw (ONJ) induced by
      bisphosphonates (BPs) and even induce this adverse effect per se. We reported a
      case of ONJ with renal cell carcinoma under sunitinib medication and history of
      BPs therapy. A 53-year-old man was referred to the oral surgery clinic
      complaining of painful exposed oral lesion and bone extraction from right lower
      jaw in the mouth. He underwent nephrectomy followed by 5 months treatment with
      cycles of 50 mg sunitinib (Sutent(r)) once a day for 4 weeks followed by 2 weeks
      drug free before lesion exposure in October 2016. However, the patient has
      encounter to intermittent mucositis and gingivitis in oral cavity several times.
      Our patient had a history of zoledronic acid (4 mg intravenously two times)
      administration due to primary cancer misdiagnosis. In our case, no dental
      procedure contributed to the occurrence of ONJ. The lesion was improved by
      sunitinib cessation and administration of antibiotics through 2 weeks. Mucosal
      injury induction as well as inhibition of angiogenic signaling pathways by
      sunitinib administration may have precipitated the occurrence of ONJ. In
      addition, a possible synergistic effect by previously BP treatment is another
      accused.

PMID- 29026846
TI  - Intracranial Hemorrhage in Methanol Toxicity: Challenging the Probable Heparin
      Effect during Hemodialysis.
AB  - Brain hemorrhages are rare complications of acute methanol poisoning. There is a
      debate on association of brain hemorrhage in methanol toxicity and application of
      systemic anticoagulation during hemodialysis (HD). A 70-year-old male presented
      to us with severe metabolic acidosis and a methanol level of 7.6 mg/dL. Ethanol
      and folinic acid were administered, and HD was performed. Brain computed
      tomography (CT) scan which was normal on presentation showed extensive bilateral
      subcortical supratentorial hypodensities on the 3rd day after commencing the
      treatment. However, the next CT scan performed 2 weeks later revealed expanding
      hemorrhagic transformation in previous hypodensities. Hemorrhagic changes could
      not be explained by patient's coagulation profile on the 3rd day. Anticoagulation
      agents such as heparin are used routinely during a dialysis session to prevent
      clot formation in dialysis circuits. This case is possibly questioning the role
      of heparin in hemorrhagic brain lesions of methanol intoxication.

PMID- 29026847
TI  - Intralesional Bevacizumab (Avastin(r)) as a Novel Addition to Infantile
      Hemangioma Management: A Medical Hypothesis.

PMID- 29026848
TI  - Drug Induced Sialorrhea and Microfluidic-Chip-Electrophoretic Analysis of
      Engorged Adult Female Tick Saliva of Haemaphysalis longicornis (Acari: Ixodidae).
AB  - BACKGROUND: The aim of the present study was to induce salivation in
      Haemaphysalis longicornis to increase saliva production and to characterize the
      collection of proteins present in the collected saliva using on-chip
      electrophoresis. METHODS: Saliva of adult female engorged H. longicornis was
      collected by treatment with 0.2% dopamine hydrochloride. All protein samples were
      characterized by SDS-PAGE electrophoresis using a microfluidic High Sensitivity
      Protein Assay 250 kit by 2100 Bioanalyzer (Agilent Technologies, USA) under non
      reducing conditions. RESULTS: The average salivary protein concentration was
      0.169 MUg/MUl/tick and saliva secretion decreased with increased time of tick
      detachment from the host. Saliva secretion volume increased to 3.56 MUl in the
      group of ticks with a body weight between 301-350 mg as compared to higher and
      lower body weight groups. On-chip-electrophoresis results show 13 distinct bands
      ranging from 9.9 to 294 kDa. CONCLUSION: Based on molecular weight, the putative
      salivary proteins are comprised of proline-rich proteins, triabin, apyrase
      members of the 12-kDa protein family, platelet inhibitors and anti-inflammatory
      proteins as tick saliva contains anti-inflammatory components.

PMID- 29026849
TI  - Increased Levels of VEGF-A and HIF-1alpha in Turkish Children with Crimean-Congo
      Hemorrhagic Fever.
AB  - BACKGROUND: Crimean-Congo Hemorrhagic Fever (CCHF) is a disease characterized by
      serious course, including acute viral fever, ecchymosis, thrombocytopenia, liver
      dysfunction and high rate of mortality. Hypoxia Inducible Factor-1alpha (HIF
      1alpha) and Vascular Endothelial Growth Factor-A (VEGF-A) play an important role
      both in the inflammatory process and plasma leakage. The aim of this study was to
      define HIF-1alpha and VEGF-A serum levels obtained from CCHF patients and control
      group and to investigate whether these factors were correlated with the
      pathogenesis of this disease. METHODS: Thirty cases younger than 17yr confirmed
      by RT-PCR and/or ELISA for CCHF were included in this study. Thirty age and sex
      matched healthy peoples were enrolled as controls. Blood samples collected from
      the patient and control groups. Serum levels of HIF-1alpha and VEGF-A were
      measured with ELISA. RESULTS: Levels of HIF-1alpha and VEGF-A were statistically
      significantly increased in CCHF patients compared to the control group (P< 0.05).
      A significant positive correlation was found between the levels of HIF-1alpha and
      VEGF-A in the patient group (P< 0.01). The levels of ALT, AST, CK, aPTT, WBC and
      Thrombocyte count were significantly higher in the patients than in the control
      group (P< 0.001). A positive correlation was found among the levels of AST and CK
      from biochemical parameters and VEGF and HIF-1alpha in the patient group (P<
      0.05). CONCLUSION: HIF-1alpha and VEGF-A might play an important role in CCHF
      pathogenesis.

PMID- 29026850
TI  - Disappearance of Anopheles minimus and Anopheles dirus from Certain Malaria
      Endemic Areas of Assam, India.
AB  - BACKGROUND: Orang Primary Health Centre (OPHC) and Balipara Primary Health Centre
      (BPHC) of Assam (India) report mosquito borne diseases annually. Current study
      was performed to ascertain the prevalence of known malaria and Japanese
      Encephalitis (JE) vectors and their possible role in disease transmission.
      METHODS: Malaria epidemiological data for 2006-2010 and JE data for 2008-2013 of
      Assam, India were obtained from the health authority. Mosquitoes were collected
      using CDC light traps and identified morpho-taxonomically. RESULTS: Plasmodium
      falciparum cases (81.5%, 95% CI= 72.0-91.1) were statistically higher in OPHC (P<
      0.0001, t= 8.0) during the recent years. There was 4.4 folds rise in the
      confirmed acute encephalitis syndrome (AES) and 3.2 folds increase in the
      confirmed JE cases during 2013 as compared to 2008. Altogether 9,218 mosquito
      specimens (PTND= 153.6), comprising of 44.1% anophelines (PTND= 67.7), 42.3%
      culicines (PTND= 65.0) and 9.5% mansonia (PTND= 14.6) were recorded. In BPHC,
      Anopheles vagus was recorded in high density (P< 0.0001), whereas Culex
      quinquefasciatus was the predominant JE vector (P= 0.04). In OPHC, among the
      known malaria vectors, the density of Anopheles annularis was significantly high
      (P< 0.0001). However Culex bitaeniorhynchus was the predominant known JE vector
      (P< 0.0001) followed by Cx. quinquefasciatus. CONCLUSION: Even in the absence of
      known efficient vectors, many Anopheles species are still involved in malaria
      transmission. There was disappearance of Anopheles minimus and Anopheles dirus
      and establishment of An. annularis, An. vagus and An. philippinensis/nivipes
      mosquitoes in study area.

PMID- 29026851
TI  - Wild Rodent Ectoparasites Collected from Northwestern Iran.
AB  - BACKGROUND: Rodents play an important role as reservoir of some pathogens, and
      the host of some ectoparasites as well. These ectoparasites can transmit rodents'
      pathogens to human or animals. The aim of this study was to assess the
      distribution and infestation load of ectoparasites on rodents in Meshkin-Shahr
      District, northwestern Iran. METHODS: Rodents were captured using baited live
      traps in spring 2014 from Meshkin-Shahr District and were transferred to the
      laboratory for identification to the species level. Their ectoparasites were
      collected, mounted and identified. RESULTS: Three rodent species including
      Meriones persicus (74%), Mus musculus (16.9%) and Cricetulus migratorius (9%)
      were identified. Among all rodents, 185 specimens (90.69%) were infested with a
      total of 521 ectoparasites. Overall, 10 arthropods species were collected,
      including fleas (97.6%), one mite (1.6%) and one louse species (0.6%) as follows:
      Xenopsylla nubica, X. astia, X. buxtoni, X. cheopis, Nosopsyllus fasciatus, N.
      iranus, Ctenocephalides felis, Ctenophthalmus rettigismiti, Ornithonyssus sp and
      one species of genus Polyplax. The most prevalent ectoparasites species was X.
      nubica (89%). CONCLUSION: Nearly all rodent species were infested with Xenopsylla
      species. Monitoring of ectoparasites on infested rodents is very important for
      awareness and early warning towards control of arthropod-borne diseases.

PMID- 29026852
TI  - Effect of Climatic Conditions and Water Bodies on Population Dynamics of the
      Dengue Vector, Aedes aegypti (Diptera: Culicidae).
AB  - BACKGROUND: The population of mosquitoes is mainly influenced by the biotic and
      abiotic factors. Although Aedes aegypti was reported until 1960's in the Punjab,
      Pakistan, the population has increased dramatically since 2009 and caused severe
      epidemics in 2011 due to heavy floods and rains. Thus, this study was carried out
      to know the effect of biotic and abiotic factors on the population of Aedes
      aegypti. METHODS: Mosquitoes were collected from fresh, sewage, and rain water
      ponds, fish ponds, rice fields, tyres, tree holes, and manmade storage containers
      present in and around residential homes twice during every winter (October
      February), summer (March-June) and monsoon season (July-September) from marked
      rural areas. RESULTS: More mosquitoes were collected in 2010 and 2011 due to
      floods than other years with heavy rains. High population (52.4%) was recorded
      during the rainy season due to high temperature (28-36  degrees C) and high
      relative humidity (up to 75%), while low population was recorded during the
      winter due to low temperature (< 5  degrees C) and low relative humidity (< 22%).
      Specimens were recorded indoors when outside temperature was below freezing
      point. Ae. aegypti was largely collected from tyres and urban areas mostly during
      the rainy season from small water containers. Years, months, seasons, temperature
      and relative humidity were statistically significant concerning the population
      dynamics of mosquitoes. CONCLUSION: Abiotic factors (temperature & relative
      humidity) along with habitat have significant impact on population dynamics of
      mosquitoes.

PMID- 29026854
TI  - A Comparative Study of Nesting Sites and Burrowing Habits of Two Iranian
      Burrowing Scorpions.
AB  - BACKGROUND: The different features of scorpions can be successfully described by
      their nesting and burrowing behaviors. There is little information about
      burrowing activity of Iranian scorpions. METHODS: The current study was performed
      to compare the burrowing behavior between two burrowing Iranian scorpions,
      Scorpio maurus and Odonthubutus bidentatus by describing 30 nests of each species
      regarding collecting the scorpions. RESULTS: Scorpio maurus and O. bidentatus
      have a tendency to make nest with elliptical, round-like entrance and oval shape
      with arch at the top, respectively. There was not any significant difference
      between nest entrance properties of two scorpions. One-way ANOVA test showed that
      the height and diameter of two species nests were not significantly different. A
      Pearson correlation also showed a relative strong direct relationship between
      height and diameter of S. maurus nests than O. bidentatus. This correlation was
      not significant in the case of O. bidentatus. The results provided additional
      habitat information of scorpions. CONCLUSION: The nests morphology
      characteristics of two Iranian scorpions including shape, depth, length and
      diameter depend are different from each other based on the following factors:
      species, soil texture, soil moisture and region conditions.

PMID- 29026853
TI  - Molecular Characterization and Phylogenetic Congruence of Hydropsyche sciligra
      (Tricoptera: Hydropsychidae) Using Mitochondrial and Nuclear Markers.
AB  - BACKGROUND: Caddisflies have significant roles in freshwater ecosystems.
      Morphological identification is the major impediment in accurate species
      identification of Hydropsychids. Mitochondrial and nuclear markers are suitable
      for molecular systematics of these group of arthropods. METHODS: Trichopteran
      specimens of Lavasan District in northeastern Tehran, Iran were collected in
      2012, and described using the morphological and molecular characters of
      mitochondrial cytochrome c oxidase subunit I (mt-COI) and three expansion
      fragments of large subunit (LSU) nuclear ribosomal DNA (28S rDNA) D1, D2, and D3.
      The resemblance of the specimen sequences was obtained by conducting BLAST
      searches against the GenBank database and by using simple maximum likelihood
      clustering using COI, D1, D2, D3, and combination of D1-D2-D3 sequence data sets.
      RESULTS: Based on morphological traits the specimens were resembled to
      Hydropsyche sciligra however there were no its counterpart sequences in the
      GenBank. Due to lack of unique group of data set for each gene fragment, the
      specimens were associated with different taxa on molecular phylograms. The
      sequence contents of the COI, D1, D2, D3, and D1-D3 regions clustered H. sciligra
      with H. brevis, H. angustipennis, H. occidentalis, H. hedini, H. grahami, and H.
      longifurca/H. naumanni, respectively. CONCLUSION: Phylogenies obtained from
      combination of D1-D3 showed the highest bootstrap values for most of clades
      suggesting that long LSU-rDNA potentially is more useful for understanding
      phylogenetic relationships of caddisflies. A large-scale molecular and
      zoogeographic study on trichopteran species is suggested to revise and to develop
      the current knowledge of the caddisfly fauna and distributions in the country.

PMID- 29026855
TI  - Insecticide Susceptibility Status of Wild-Caught Sand Fly Populations Collected
      from Two Leishmaniasis Endemic Areas in Western Turkey.
AB  - BACKGROUND: In Turkey, vector control programs are mainly based on indoor
      residual spraying with pyrethroids against mosquitoes. No special control program
      is available for sand flies. Most insecticide susceptibility tests were done for
      mosquitoes but not for sand flies. We therefore aimed to determine the
      insecticide susceptibility against two commonly used insecticides; deltamethrin
      and permethrin, on wild-caught sand fly populations collected in two
      geographically separated leishmaniasis endemic areas. METHODS: Insecticide
      susceptibility of wild-caught sand flies to deltamethrin (0.05%) and permethrin
      (0.75%) using ready-to use impregnated insecticide papers of WHO was investigated
      in 2010 based on knockdown time using standard WHO tube-test kit and procedures.
      Sand flies used in this study were collected from villages of Aydin (Bascayir)
      and Mugla (Tepecik). RESULTS: The resistance and early resistance were detected
      on the sand fly population from Mugla province against deltamethrin and
      permethrin, respectively. However, populations from Aydin Province were sensitive
      to both insecticides. CONCLUSION: The resistance against deltamethrin and
      permethrin was detected on sand fly population in Mugla Province where both
      insecticides have been applied for long time while no resistance was found in the
      insecticide free area, Aydin Province. These findings can be an indicator for
      showing the ability for developing the insecticide resistance in sand flies.
      Because of the presence and dominancy of vector sand fly species of Leishmania
      infantum (Phlebotomus neglectus, P. tobbi) in both study areas, the systematic
      monitoring for resistance of sand fly populations and more attention are needed
      by the authorities involved in control programs for sand fly-borne diseases.

PMID- 29026856
TI  - Synthesis and Comparison of In Vitro Leishmanicidal Activity of 5
      (Nitroheteroaryl)-1,3,4-Thiadiazols Containing Cyclic Amine of Piperidin-4-ol at
      C-2 with Acyclic Amine Analogues against Iranian Strain of Leishmania major
      (MRHO/IR/75/ER).
AB  - BACKGROUND: Cutaneous Leishmaniasis (CL) is endemic in many tropical and
      subtropical regions of the world. Due to the prolonged duration of therapy,
      adverse effect and resistance to current drugs in the treatment of CL, the
      discovery of novel, efficient, and safe leishmanicidal drugs is required. The
      aims of the present study was to synthesis of new compounds based on the active
      compounds of 5-(5-nitrofuran-2-yl)- and 5-(5-nitrothiophen-2-yl)-1,3,4
      thiadiazole bearing the linear amino alcohol of 3-aminopropan-1-ol in the C-2
      position of thiadiazole ring and evaluation of their activity against the
      promastigote and amastigote forms of Leishmania major. METHODS: Reaction between
      the solution of 5-(5-nitro heteroaryl)-2-chloro-1,3,4-thiadiazole and piperidin-4
      ol in absolute ethanol was performed and the resulting products were evaluated
      against promastigotes form of L. major with MTT assay and amastigote form of L.
      major in murine peritoneal macrophages. In addition, the toxicity of these
      compounds was assessed against mouse peritoneal macrophages with MTT assay.
      RESULTS: New synthetic compounds 5a-b showed moderate in vitro antileishmanial
      activity against L. major promastigotes with IC50 values of 68.9 and 27MUM,
      respectively. These compounds have also demonstrated a good antiamastigote
      activity in terms of amastigote number per macrophage, the percentage of
      macrophage infectivity and infectivity index. CONCLUSION: Novel cyclic compounds
      5a-b were synthesized and exhibited less antipromastigote and antiamastigote
      activity compared to linear analogues.

PMID- 29026857
TI  - Repellency Effect of Essential Oils of some Native Plants and Synthetic
      Repellents against Human Flea, Pulex irritans (Siphonaptera: Pulicidae).
AB  - BACKGROUND: Fleas are important vectors of human and animal disease, and control
      measures for protection against their bites and flea-borne diseases are
      necessary. METHODS: The essential oils (EOs) of four native medicinal plants,
      Ziziphora tenuiore, Myrtus communis, Achillea wilhelmsii and Mentha piperita were
      isolated by hydrodistillation technique and analyzed by GC-MC. The repellent
      activity of EOs and synthetic compounds, DEET and permethrin, were assayed on
      human subjects against field collected fleas. The effective doses of 50% and 90%
      of EOs and synthetic compounds were estimated by probit analysis of dose and
      response regression line. RESULTS: Analysis of EOs revealed about 19 major
      components. All oils were found to be more repellent (ED50 range= 208-955MUg cm
      2) than DEET and permethrin (ED50 range= 27-182 * 103MUg cm-2). Thyme and myrtle
      oils showed high repellent activities and among the total detected terpenes,
      thymol (36.26%) and alpha-pinene (32.5%) were the major components of those oils
      respectively. CONCLUSION: Low repellent potency of DEET and permethrin against
      fleas might be related to flea olfactory system and further molecular and
      electrophysiological studies are required to conceive new ideas for the discovery
      and development of the next generation of repellents. Based on high repellent
      activity of thyme and myrtle essential oils against Pulex irritans further
      studies should be staged to develop their appropriate effective formulations.
      Likewise, field trials should be carried out to evaluate the operational
      feasibility and dermal toxicity over a long period.

PMID- 29026858
TI  - Chemical Constitute and Larvicidal Activity of Fractions of Ajuga chamaecistus
      tomentella Plant against Malaria Vector Anopheles stephensi.
AB  - BACKGRAND: The genus Ajuga, belongs to Lamiaceae family, is one of the exclusive
      subspecies in the flora of Iran. The plants of this genus are used traditionally
      for treatment of joints pain, gout, jaundice, and as insecticide. METHODS:
      larvicidal activity of methanol 80% extract and partition fractions of hexane,
      chloroform, and ethyl acetate obtained from aerial parts of Ajuga chamaecistus
      subspecies tomentella against malaria vector An. stephensi was evaluated.
      Phytochemical study of active fraction was analyzed using column chromatography
      and spectroscopy. RESULTS: According to the results, among different fractions,
      hexane fraction has the most larvicidal activity with mortality rate of 100% in
      concentration of 102 ppm and LC50 of 95.66ppm. The structure of compound 1, main
      phytoecdysteroid compound separated from hexane fraction, was determined to be
      ajugalide-E. CONCLUSION: The results suggested that the hexane fraction of Ajuga
      chamaecistus subsp tomentella could be used as a natural and biodegradable
      insecticide.

PMID- 29026859
TI  - Molecular Identification of Leishmania Species in a Re-Emerged Focus of Cutaneous
      Leishmaniasis in Varamin District, Iran.
AB  - BACKGROUND: Cutaneous leishmaniasis (CL) is one of the most important neglected
      tropical diseases and a major public health challenge in Iran caused by
      Leishmania spp and transmitted by phlebotomine sand flies. The number of CL cases
      has shown an increasing pattern all over the country, including the district of
      Varamin, southeast of Tehran, Iran. This study aimed to identify the Leishmania
      spp isolated from CL patients using molecular methods in Varamin during 2012
      2013. METHODS: Exudate materials collected from the swollen edge of the skin
      lesions of 44 parasitological positive CL patients by disposable lancet. They
      were referred to Varamin Health Center by physician. The samples were subjected
      to molecular method for Leishmania species identification. RESULTS: The digestion
      pattern of restriction enzyme revealed that 37 (84.1%) CL patients were infected
      with L. major and 7 (15.9%) were infected with L. tropica. They were mostly male
      than female. More than half of the patients (58%) had multiple lesions, and they
      were mostly observed on extremities, 34.1% on legs and 29.5% on hands. Lesions
      were mostly of wet ulcerative type. CONCLUSION: Dominancy of L. major provides
      more evidence that Varamin District probably could be considered as Zoonotic
      Cutaneous Leishmaniasis (ZCL) areas. More investigation on other epidemiological
      aspects of disease is needed.

PMID- 29026861
TI  - Presence of Phlebotomus perniciosus Atypical Form in Algeria.
AB  - BACKGROUND: Phlebotomus perniciosus and Phlebotomus longicuspis are two
      phlebotomine sand fly species morphologically similar and differing in males only
      by the shape of the copulatory valves which are bifurcated in P. perniciosus, tip
      long and tapered in P. longicuspis. METHODS: A count of the median coxite setae
      was carried out on 208 specimens from the collections of Dedet and of Parrot,
      identified previously as P. longicuspis and on 38 P. perniciosus male sand flies
      captured during the year 2012-2013, in order to seek the presence of atypical P.
      perniciosus form. RESULTS: The analysis revealed the presence of 33/246 (13%)
      atypical P. perniciosus previously confused with P. longicuspis species and whose
      distribution is mainly located in the semi-arid and arid bioclimatic regions.
      CONCLUSION: This study proved for the first time the presence of atypical form of
      P. perniciosus in Algeria.

PMID- 29026862
TI  - Bioefficacy of Some Egyptian Aromatic Plants on Culex pipiens (Diptera:
      Culicidae) Adults and Larvae.
AB  - BACKGROUND: Protecting the environment from chemical hazards of synthetic
      insecticides along with offering of new breeding areas for vectors by
      urbanization indicate the trial of natural insecticides. METHODS: The acetone
      extracts of Anethum graveolens, Ocimum basilicum and Thymus vulgaris were tested
      for their insecticidal effect on Culex pipiens adults and larvae in different
      concentrations depending on the technique used. RESULTS: The extracts were
      significantly effective in all models used with basil being the best in all
      tested three techniques (LC50= 0.064) in larval feeding, (LC50= 0.330) in CDC
      bottle assay and (LC50= 13.148) in adults feeding (P< 0.05). CONCLUSION: The
      results recommend the eco-friendly studied extracts as candidates for controlling
      Cx. pipiens the lymphatic filariasis vector.

PMID- 29026860
TI  - Evaluation of Correlation between the In Vitro Susceptibility of Field Isolates
      of Leishmania major and Clinical Outcomes of Meglumine Antimoniate Therapy in
      Fars Province, Iran.
AB  - BACKGROUND: This study was designed to detect whether there is a correlation
      between in vitro susceptibility of field isolates of Leishmania major and the
      clinical outcomes of meglumine antimoniate (Glucantime(r)) therapy, the mainstay
      of cutaneous leishmaniasis treatment in Iran. METHODS: Forty-three patients
      infected with L. major were enrolled in this study from October 2009 to March
      2010 and categorized as responsive or unresponsive to Glucantime(r) treatment
      after receiving the appropriate therapy. Then, intracellular amastigote approach
      was conducted on these field strains to investigate in vitro drug susceptibility
      as well. RESULTS: At clinical level, out of 43 patients, 15 were clinically non
      responsive and 28 were responsive to antimony therapy. All those 28 clinically
      sensitive strains were susceptible to antimony in the in vitro assay, whereas
      merely 11 isolates from 15 non-healing isolates were resistant in vitro. Finally,
      a good correlation (78.9%) with high sensitivity, specificity (100/73) between
      clinical outcomes and the in vitro susceptibility test was achieved. CONCLUSION:
      The intracellular amastigote model could be an appropriate assay for evaluation
      of the in vivo drug sensitivity of field isolates. However, more comprehensive
      studies with larger sets of isolates are needed to confirm these preliminary
      data.

PMID- 29026863
TI  - Assessing the Ovarian Accessory Glands to Determine the Parity of Phlebotomus
      papatasi, Vector of Zoonotic Cutaneous Leishmaniasis, under Laboratory Condition.
AB  - BACKGROUND: Zoonotic cutaneous leishmaniasis (ZCL) is a neglected tropical
      disease prevailed in many rural areas of 17 out of 31 provinces in Iran. The main
      vector of the disease is Phlebotomus papatasi and the causative agent is
      Leishmania major in ZCL foci of Iran. In the current study we investigated the
      validity of accessory glands secretions as an indicator to recognize parous from
      nulliparous Ph. papatasi females under laboratory conditions. METHODS: Over 235
      laboratory-reared females of Ph. papatasi were dissected in 6 groups including:
      newly emerged, one hour, one day, two days, and three days after blood feeding
      and also after oviposition under stereo microscope for their parity in 2014-2015.
      RESULTS: Transparent glands were compatible with nulliparous only in newly
      emerged sand flies. In sand flies dissected after oviposition, accessory glands
      were rather large as a result of oviposition though they were transparent.
      CONCLUSION: The accessory glands secretions could not be as an indicator for
      distinguishing parous from nulliparous of Ph. papatasi females.

PMID- 29026864
TI  - Gastroparesis as the Sole Presenting Feature of Neuromyelitis Optica.
AB  - A 33-year-old African-American woman recently diagnosed with severe idiopathic
      gastroparesis was readmitted for hypoxic respiratory failure secondary to
      aspiration pneumonia. A fiber-optic endoscopic evaluation of swallow study
      revealed severe pharyngeal dysphagia. Brain magnetic resonance imaging showed an
      ill-defined lesion in the posterior aspect of the medulla concerning for a
      demyelinating process. Serum neuromyelitis optica immunoglobulin G returned
      positive. Neuromyelitis optica treatment resulted in the patient's clinical
      improvement. She is currently on a suppressive regimen of intravenous rituximab
      and is recovering well.

PMID- 29026865
TI  - Rare Gastric Cardia Polyp Causing Complete Esophageal Obstruction.
AB  - A 67-year-old man presented with food impaction and was found to have a gastric
      polyp obstructing the esophageal outlet. Due to the polyp's location and size, no
      immediate endoscopic intervention was performed, and the patient returned for
      intraoperative endoscopy and polypectomy. Cases of gastric polyps causing
      esophageal obstruction have not been identified in the literature. This case is
      unique for the location and size of the polyp, necessitating concomitant surgical
      management.

PMID- 29026867
TI  - Prevalence of Carbapenem-Resistant Gram-Negative Infections in the United States
      Predominated by Acinetobacter baumannii and Pseudomonas aeruginosa.
AB  - BACKGROUND: Carbapenem-resistant (CR) Gram-negative pathogens are recognized as a
      major health concern. This study examined the prevalence of infections due to 4
      CR Gram-negative species (Acinetobacter baumannii, Pseudomonas aeruginosa,
      Klebsiella pneumoniae, and Escherichia coli) in the United States and assessed
      their impact on hospital stays and mortality. METHODS: Hospitalized patients with
      laboratory-confirmed infection due to any of the 4 Gram-negative pathogens were
      identified from the Premier Healthcare Database. Proportions of CR were
      calculated by pathogen and infection site (blood, respiratory, urinary, or other)
      for the United States as whole and by census regions. Crude and adjusted odds
      ratios for in-hospital mortality were produced using logistic regression.
      RESULTS: From 2009 to 2013, 13 262 (4.5%) of 292 742 infections due to these 4
      Gram-negative pathogens were CR. Of these CR infections, 82.3% were caused by A.
      baumannii (22%) or P. aeruginosa (60.3%), while 17.7% were caused by K.
      pneumoniae or E. coli. CR patients had longer hospital stays than carbapenem
      susceptible (CS) patients in all pathogen-infection site cohorts, except in the
      A. baumannii-respiratory cohort. The crude all cause in-hospital mortality was
      greater for most pathogen-infection site cohorts of the CR group compared with
      the CS group, especially for A. baumannii infection in the blood (crude odds
      ratio [OR], 3.91; 95% confidence interval [CI], 2.69-5.70). This difference for
      the A. baumannii-blood cohort remained after adjusting for the relevant
      covariates (adjusted OR, 2.46; 95% CI, 1.43-4.22). CONCLUSION: The majority of CR
      infections and disease burden in the United States was caused by nonfermenters A.
      baumannii and P. aeruginosa. Patients with CR infections had longer hospital
      stays and higher crude in-hospital mortality.

PMID- 29026868
TI  - Antifungal Susceptibility Testing Practices at Acute Care Hospitals Enrolled in
      the National Healthcare Safety Network, United States, 2011-2015.
AB  - We assessed availability of antifungal susceptibility testing (AFST) at nearly
      4000 acute care hospitals enrolled in the National Healthcare Safety Network. In
      2015, 95% offered any AFST, 28% offered AFST at their own laboratory or at an
      affiliated medical center, and 33% offered reflexive AFST. Availability of AFST
      improved from 2011 to 2015, but substantial gaps exist in the availability of
      AFST.

PMID- 29026866
TI  - A Prospective Observational Study of the Epidemiology, Management, and Outcomes
      of Skin and Soft Tissue Infections Due to Carbapenem-Resistant
      Enterobacteriaceae.
AB  - BACKGROUND: This study was performed to characterize the epidemiology,
      management, and outcomes of skin and soft tissue infection (SSTI) and
      colonization due to carbapenem-resistant Enterobacteriaceae (CRE). METHODS:
      Patients from the Consortium on Resistance Against Carbapenem in Klebsiella and
      Other Enterobacteriaceae (CRACKLE-1) from December 24, 2011 to October 1, 2014
      with wound cultures positive for CRE were included in the study. Predictors of
      surgical intervention were analyzed. Molecular typing of isolates was performed
      using repetitive extragenic palindromic polymerase chain reaction (PCR).
      Carbapenemase genes were detected using PCR. RESULTS: One hundred forty-two
      patients were included: 62 had SSTI (44%) and 56% were colonized. Mean age was 61
      years, and 48% were male: median Charlson score was 3 (interquartile range, 1-5).
      Forty-eight percent of patients were admitted from long-term care facilities
      (LTCFs), and 31% were from the community. Two strain types (ST258A and ST258B)
      were identified (73% of 45 tested). Carbapenemase genes were detected in 40 of 45
      isolates (blaKPC-3 [47%], blaKPC-2 [42%]). Sixty-eight patients (48%) underwent
      surgical intervention, 63% of whom had SSTI. Patients admitted from LTCFs were
      less likely to undergo surgical intervention (odds ratio [OR], 0.36; 95%
      confidence interval [CI], 0.18-0.71). In multivariable analysis, among patients
      with SSTI, those admitted from LTCFs were less likely to undergo debridement (OR,
      0.18; 95% CI, 0.04-0.93). CONCLUSIONS: Patients admitted from LTCFs with CRE SSTI
      were less likely to undergo surgical intervention. Sixteen percent of the
      patients died, and approximately 50% of survivors required more intensive care
      upon discharge. These findings suggest a unique, impactful syndrome within the
      CRE infection spectrum. Further studies are needed to assess the role of surgical
      debridement in management of CRE-SSTI, particularly among LTCF residents.

PMID- 29026870
TI  - Comparing Injecting Drug Users with Others Receiving Outpatient Parenteral
      Antibiotic Therapy.

PMID- 29026869
TI  - Associations Between Antiretroviral Treatment and Avascular Bone Necrosis: The
      Swiss HIV Cohort Study.
AB  - BACKGROUND: HIV-infected individuals have an increased risk of avascular bone
      necrosis (AVN). Antiretroviral therapy (ART) and particularly protease inhibitors
      (PI) have been implicated as a risk factor. We aimed to study the associations of
      ART with the occurrence of AVN among Swiss HIV Cohort Study participants (SHCS).
      METHODS: We used incidence density sampling to perform a case control study
      within the Swiss HIV Cohort Study (SHCS) comparing prospectively collected AVN
      cases and controls by conditional logistic regression analysis. To evaluate the
      effect of ART, multivariable models were adjusted for HIV transmission risk
      group, age, alcohol consumption, use of corticosteroids, CD4 nadir, maximum viral
      load, and pancreatitis. RESULTS: We compared 74 AVN cases and 145 controls.
      Associations with AVN were shown for heterosexual HIV acquisition (odds ratio
      [OR], 3.4; 95% confidence interval [CI], 1.1-10), alcohol consumption (OR, 2.7;
      95% CI, 1.3-5.7), and hyperlipidemia (OR, 3.6; 95% CI, 1.4-9.6). After adding ART
      substances to the multivariable base model, there was evidence of an association
      for treatment with tenofovir (TDF) >1 year (OR, 4.4; 95% CI, 1.4-14) with AVN.
      Neither exposure to specific frequently prescribed ART combinations or ART drug
      classes nor cumulative ART exposure showed any associations with AVN.
      CONCLUSIONS: In the HIV-infected population, a combination of risk factors such
      as heterosexual HIV acquisition, moderate to severe alcohol intake, and
      hyperlipidemia seem to contribute to AVN. ART does not seem to be a relevant risk
      factor for AVN. The association of prolonged TDF exposure with AVN needs to be
      confirmed.

PMID- 29026871
TI  - Tigecycline as a Second-Line Agent for Legionnaires' Disease in Severely Ill
      Patients.
AB  - Treatment of Legionnaires' disease in severely ill or immunosuppressed patients
      presents a clinical challenge. Tigecycline (TG) achieves high concentrations
      intracellularly and has been shown to be effective against L. pneumophila in
      animal and cell models. We report our experience using TG as second-line therapy.
      Clinical response was seen in most patients after switching to TG alone or as a
      combination therapy.

PMID- 29026872
TI  - Top Questions in ID: Pre-exposure Prophylaxis for HIV.
AB  - HIV pre-exposure prophylaxis (PrEP) is highly efficacious at preventing HIV
      acquisition. This review discusses ways to identify candidates for PrEP,
      recommended PrEP regimens, baseline and follow-up evaluations, applications of
      PrEP for HIV-serodiscordant couples, resources to address financial barriers,
      investigational strategies for PrEP, and educational resources for clinicians and
      patients.

PMID- 29026874
TI  - Australia and New Zealand Islets and Pancreas Transplant Registry Annual Report
      2017-Pancreas Waiting List, Recipients, and Donors.
AB  - This is a registry report from the Australia and New Zealand Islet and Pancreas
      Transplant Registry. We report data for all solid organ pancreas transplant
      activity from inception in 1984 to end of 2016. Data analysis was performed using
      Stata Software version 14 (StataCorp, College Station, Tex). From 1984 to 2016 a
      total of 756 solid organ pancreas transplants have been performed in Australia
      and New Zealand, in 738 individuals. In 2016, 55 people received a pancreas
      transplant. These transplants were performed in Auckland (4), Monash (22), and
      Westmead (29). In 2016, 50 transplants were simultaneous pancreas kidney, 4 were
      pancreas after kidney, and 1 was a pancreas transplant alone.

PMID- 29026875
TI  - Ethylene Glycol Poisoning Should Not Contraindicate Liver Donation.
AB  - As the number of patients waiting to receive transplants increases, there is a
      need to explore all possible donation opportunities. In this case report, we
      describe the transplantation of a liver from a donor who died after ethylene
      glycol poisoning into a woman with alcoholic liver disease with cirrhosis and
      associated ascites. Donor management, including ethanol, fomepizol and
      haemodialysis, hastened clearance of ethylene glycol from the circulation, and
      after liver transplantation, the recipient exhibited no adverse effects
      suggestive of ethylene glycol toxicity, although recipient hepatic artery
      dissection and thrombosis necessitated retransplantation. Our experience suggests
      that donor death due to ethylene glycol intoxication should not contraindicate
      liver transplantation, particularly after appropriate donor management.

PMID- 29026873
TI  - Graft Growth and Podocyte Dedifferentiation in Donor-Recipient Size Mismatch
      Kidney Transplants.
AB  - BACKGROUND: Kidney transplantation is the treatment choice for patients with end
      stage renal diseases. Because of good long-term outcome, pediatric kidney grafts
      are also accepted for transplantation in adult recipients despite a significant
      mismatch in body size and age between donor and recipient. These grafts show a
      remarkable ability of adaptation to the recipient body and increase in size in a
      very short period, presumably as an adaptation to hyperfiltration. METHODS: We
      investigated renal graft growth as well as glomerular proliferation and
      differentiation markers Kiel-67, paired box gene 2 and Wilms tumor protein (WT1)
      expression in control biopsies from different transplant constellations: infant
      donor for infant recipient, infant donor for child recipient, infant donor for
      adult recipient, child donor for child recipient, child donor for adult
      recipient, and adult donor for an adult recipient. RESULTS: We detected a
      significant increase in kidney graft size after transplantation in all conditions
      with a body size mismatch, which was most prominent when an infant donated for a
      child. Podocyte WT1 expression was comparable in different transplant conditions,
      whereas a significant increase in WT1 expression could be detected in parietal
      epithelial cells, when a kidney graft from a child was transplanted into an
      adult. In kidney grafts that were relatively small for the recipients, we could
      detect reexpression of podocyte paired box gene 2. Moreover, the proliferation
      marker Kiel-67 was expressed in glomerular cells in grafts that increased in size
      after transplantation. CONCLUSIONS: Kidney grafts rapidly adapt to the recipient
      size after transplantation if they are transplanted in a body size mismatch
      constellation. The increase in transplant size is accompanied by an upregulation
      of proliferation and dedifferentiation markers in podocytes. The different
      examined conditions exclude hormonal factors as the key trigger for this growth
      so that most likely hyperfiltration is the key trigger inducing the rapid growth
      response.

PMID- 29026877
TI  - Prolonged Delayed Renal Graft Function Secondary to Venous Hypertension.
AB  - The case of a 39-year-old highly sensitized woman who underwent second renal
      transplantation after being on warfarin because of a history of frequent
      thromboses of her left femoral arteriovenous graft (AVG) is reported here. The
      patient received a flow cytometric positive crossmatch kidney transplant from a
      deceased donor. Her posttransplant course was complicated by prolonged delayed
      graft function (DGF) lasting for 9 months. Antibody-mediated rejection occurred
      in the immediate postoperative period. This resolved after treatment, and
      resolution was confirmed by repeat biopsy. Despite this, she had persistent DGF
      and remained dialysis dependent. A computed tomography scan due to the
      development of perinephric hematoma after posttransplant biopsy demonstrated
      venous collateralization around the allograft. At 7 months posttransplant, a
      venogram during declotting of AVG revealed chronic thrombus in the inferior vena
      cava (IVC) above the level of native renal veins with a venous gradient of 26
      mmHg. After declotting of the graft, iliac venoplasty, and subsequent IVC stent,
      her renal function continues to improve with a most recent creatinine of 1.4
      mg/dL at 36 months posttransplant. Venous hypertension secondary to IVC
      thrombosis in presence of patent femoral AVG should be considered as a rare cause
      of prolonged DGF.

PMID- 29026876
TI  - Avoiding ICU Admission by Using a Fast-Track Protocol Is Safe in Selected Adult
      to-Adult Live Donor Liver Transplant Recipients.
AB  - BACKGROUND: We evaluated patient characteristics of live donor liver transplant
      (LDLT) recipients undergoing a fast-track protocol without intensive care unit
      (ICU) admission versus LDLT patients receiving posttransplant ICU care. METHODS:
      Of the 153 LDLT recipients, 46 patients were included in our fast-track protocol
      without ICU admission. Both, fast-tracked patients and ICU-admitted patients were
      compared regarding donor and patient characteristics, perioperative
      characteristics, and postoperative outcomes and complications. In a subgroup
      analysis, we compared fast-tracked patients with patients who were admitted in
      the ICU for less than 24 hours. RESULTS: Fast-tracked versus ICU patients had a
      lower model for end-stage liver disease score (13 +/- 4 vs 18 +/- 7; P < 0.0001),
      lower preoperative bilirubin levels (51 +/- 50 MUmol/L vs 119.4 +/- 137.3
      MUmol/L; P < 0.001), required fewer units of packed red blood cells (1.7 +/- 1.78
      vs 4.4 +/- 4; P < 0.0001), and less fresh-frozen plasma (2.7 +/- 2 vs 5.8 +/- 5;
      P < 0.0001) during transplantation. Regarding postoperative outcomes, fast
      tracked patients presented fewer bacterial infections within 30 days (6.5% [3] vs
      29% [28]; P = 0.002), no episodes of pneumonia (0% vs 11.3% [11]; P = 0.02), and
      less biliary complications within the first year (6% [3] vs 26% [25]; P = 0.001).
      Also, fast-tracked patients had a shorter posttransplant hospital stay (10.8 +/-
      5 vs 21.3 +/- 29; P = 0.002). In the subgroup analysis, fast-tracked vs ICU
      patients admitted for less than 24 hours had lower requirements of packed red
      blood cells (1.7 +/- 1.78 vs 3.9 +/- 4; P = 0.001) and fresh-frozen plasma (2.7
      +/- 2 vs 5.8 +/- 4.5; P = 0.0001). CONCLUSIONS: Fast-track of selected patients
      after LDLT is safe and feasible. An objective score to perioperatively select
      LDLT recipients amenable to fast track is yet to be determined.

PMID- 29026878
TI  - Robotic-Assisted Live Donor Ileal Segmentectomy for Intestinal Transplantation.
AB  - BACKGROUND: Every effort should be made to optimize surgical techniques and to
      minimize potential morbidity rates associated with live donor operations.
      Advances in a minimally invasive approach by robotic surgery to donor nephrectomy
      have raised the possibility of applying this technique to live donor bowel
      resections for intestinal transplantation. METHODS: We report the first 5
      consecutive cases of a robotic-assisted live donor ileal segmentectomy. We
      describe the technical aspects of the procedure, discuss the rationale for
      considering this option, and evaluate potential advantages of this approach.
      RESULTS: We found that this new approach is associated with less postoperative
      discomfort, a shorter hospital length of stay, and a faster recovery of bowel
      function compared to our previous open surgery. CONCLUSIONS: Our initial
      experience suggests that robotic surgery is a safe and feasible procedure for
      live donor ileal resection for intestinal transplantation and is a useful
      alternative to conventional open surgery.

PMID- 29026879
TI  - Tsunamis in the geological record: Making waves with a cautionary tale from the
      Mediterranean.
AB  - From 2000 to 2015, tsunamis and storms killed more than 430,000 people worldwide
      and affected a further >530 million, with total damages exceeding US$970 billion.
      These alarming trends, underscored by the tragic events of the 2004 Indian Ocean
      catastrophe, have fueled increased worldwide demands for assessments of past,
      present, and future coastal risks. Nonetheless, despite its importance for hazard
      mitigation, discriminating between storm and tsunami deposits in the geological
      record is one of the most challenging and hotly contended topics in coastal
      geoscience. To probe this knowledge gap, we present a 4500-year reconstruction of
      "tsunami" variability from the Mediterranean based on stratigraphic but not
      historical archives and assess it in relation to climate records and
      reconstructions of storminess. We elucidate evidence for previously unrecognized
      "tsunami megacycles" with three peaks centered on the Little Ice Age, 1600, and
      3100 cal. yr B.P. (calibrated years before present). These ~1500-year cycles,
      strongly correlated with climate deterioration in the Mediterranean/North
      Atlantic, challenge up to 90% of the original tsunami attributions and suggest,
      by contrast, that most events are better ascribed to periods of heightened
      storminess. This timely and provocative finding is crucial in providing
      appropriately tailored assessments of coastal hazard risk in the Mediterranean
      and beyond.

PMID- 29026881
TI  - Herbivory enables marine communities to resist warming.
AB  - Climate change can influence ecosystems via both direct effects on individual
      organisms and indirect effects mediated by species interactions. However, we
      understand little about how these changes will ripple through ecosystems or
      whether there are particular ecological characteristics that might make
      ecosystems more susceptible-or more resistant-to warming. By combining in situ
      experimental warming with herbivore manipulations in a natural rocky intertidal
      community for over 16 months, we show that herbivory regulates the capacity of
      marine communities to resist warming. We found that limpet herbivores helped to
      preserve trophic and competitive interactions under experimental warming,
      dampening the impact of warming on overall community composition. The presence of
      limpets facilitated the survival of the main habitat modifier (barnacles) under
      warmer conditions, which, in turn, facilitated the presence of a consumer guild.
      When limpets were removed, environmental warming altered trophic, competitive,
      and facilitative interactions, with cascading impacts on community succession and
      stability. We conclude that conserving trophic structure and the integrity of
      interaction networks is vitally important as Earth continues to warm.

PMID- 29026880
TI  - Adaptive social strategies in a solitary carnivore.
AB  - Cost-benefit trade-offs for individuals participating in social behaviors are the
      basis for current theories on the evolution of social behaviors and societies.
      However, research on social strategies has largely ignored solitary animals, in
      which we assume that rare interactions are explained by courtship or
      territoriality or, in special circumstances, resource distributions or kinship.
      We used directed network analysis of conspecific tolerance at food sources to
      provide evidence that a solitary carnivore, the puma (Puma concolor), exhibited
      adaptive social strategies similar to more social animals. Every puma in our
      analysis participated in the network, which featured densely connected
      communities delineated by territorial males. Territorial males also structured
      social interactions among pumas. Contrary to expectations, conspecific tolerance
      was best characterized by direct reciprocity, establishing a fitness benefit to
      individuals that participated in social behaviors. However, reciprocity operated
      on a longer time scale than in gregarious species. Tolerance was also explained
      by hierarchical reciprocity, which we defined as network triangles in which one
      puma (generally male) received tolerance from two others (generally females) that
      also tolerated each other. Hierarchical reciprocity suggested that males might be
      cheating females; nevertheless, we suspect that males and females used different
      fitness currencies. For example, females may have benefited from tolerating males
      through the maintenance of social niches that support breeding opportunities. Our
      work contributes evidence of adaptive social strategies in a solitary carnivore
      and support for the applicability of theories of social behavior across taxa,
      including solitary species in which they are rarely tested.

PMID- 29026882
TI  - Efficient measurement and factorization of high-order drug interactions in
      Mycobacterium tuberculosis.
AB  - Combinations of three or more drugs are used to treat many diseases, including
      tuberculosis. Thus, it is important to understand how synergistic or antagonistic
      drug interactions affect the efficacy of combination therapies. However, our
      understanding of high-order drug interactions is limited because of the lack of
      both efficient measurement methods and theoretical framework for analysis and
      interpretation. We developed an efficient experimental sampling and scoring
      method [diagonal measurement of n-way drug interactions (DiaMOND)] to measure
      drug interactions for combinations of any number of drugs. DiaMOND provides an
      efficient alternative to checkerboard assays, which are commonly used to measure
      drug interactions. We established a geometric framework to factorize high-order
      drug interactions into lower-order components, thereby establishing a road map of
      how to use lower-order measurements to predict high-order interactions. Our
      framework is a generalized Loewe additivity model for high-order drug
      interactions. Using DiaMOND, we identified and analyzed synergistic and
      antagonistic antibiotic combinations against Mycobacteriumtuberculosis. Efficient
      measurement and factorization of high-order drug interactions by DiaMOND are
      broadly applicable to other cell types and disease models.

PMID- 29026883
TI  - Increased weight gain by C-section: Functional significance of the primordial
      microbiome.
AB  - Epidemiological evidence supports a direct association between early microbiota
      impact-including C-section-and obesity. We performed antibiotic-free, fostered C
      sections and determined the impact on the early microbiota and body weight during
      development. Mice in the C-section group gained more body mass after weaning,
      with a stronger phenotype in females. C-section-born mice lacked the dynamic
      developmental gut microbiota changes observed in control mice. The results
      demonstrate a causal relationship between C-section and increased body weight,
      supporting the involvement of maternal vaginal bacteria in normal metabolic
      development.

PMID- 29026884
TI  - Review of the potential use of blood neuro-biomarkers in the diagnosis of mild
      traumatic brain injury.
AB  - Head injury is a common presenting complaint amongst emergency department
      patients. To date, there has been no widespread utilization of neuro-biomarkers
      to aid the diagnosis of traumatic brain injury. This review article explores
      which neuro-biomarkers could be used in the emergency department in aiding the
      clinical diagnosis of mild traumatic brain injury. Based on the available
      evidence, the most promising neuro-biomarkers appear to be Glial fibrillary
      acidic protein (GFAP) and Ubiquitin C-Terminal Hydrolase Isozyme L1 (UCH-L1) as
      these show significant rises in peripheral blood levels shortly after injury and
      these have been demonstrated to correlate with long-term clinical outcomes.
      Treatment strategies for minor traumatic brain injury in the emergency department
      setting are not well developed. The introduction of blood neuro-biomarkers could
      reduce unnecessary radiation exposure and provide an opportunity to improve the
      care of this patient group.

PMID- 29026885
TI  - Emergency department point-of-care ultrasonography improves time to
      pericardiocentesis for clinically significant effusions.
AB  - OBJECTIVE: Our objective was to determine the utility of point-of-care ultrasound
      (POCUS) to identify and guide treatment of tamponade or clinically significant
      pericardial effusions in the emergency department (ED). METHODS: This was a
      retrospective cohort study of non-trauma patients who were diagnosed with large
      pericardial effusions or tamponade by the ED physician using POCUS. The control
      group was composed of those patients later diagnosed on the medical wards or
      incidentally in the ED by other means such as a computed tomography. The
      following data were abstracted from the patient's file: demographics, medical
      background, electrocardiogram results, chest radiograph readings, echocardiogram
      results, and patient outcomes. RESULTS: There were 18 patients in the POCUS arm
      and 55 in the control group. The POCUS arm had a decreased time to
      pericardiocentesis (11.3 vs. 70.2 hours, P=0.055) as well as a shorter length of
      stay (5.1 vs. 7.0 days, P=0.222). A decreased volume of pericardial fluid was
      drained (661 vs. 826 mL, P=0.139) in the group diagnosed by POCUS. CONCLUSION:
      This study suggests that POCUS may effectively identify pericardial effusions and
      guide appropriate treatment, leading to a decreased time to pericardiocentesis
      and decreased length of hospital stay. Pericardial tamponade or a large
      pericardial effusion should be considered in all patients presenting to the ED
      with clinical, radiographic, or electrocardiographic signs of cardiovascular
      compromise.

PMID- 29026886
TI  - Clinical characteristics of acute drug-induced dystonia in pediatric patients.
AB  - OBJECTIVE: Dystonia is a movement disorder in which muscles contract
      uncontrollably. Acute drug-induced dystonia (DID) can be diagnosed through
      detailed history taking and physical examination. This study aimed to identify
      the clinical characteristics of DID in children, which could help emergency
      physicians diagnose these conditions more efficiently. METHODS: We reviewed
      medical records of children aged below 18 years diagnosed with drug-related
      dystonia after discharge from the emergency department over 10 years. We
      collected the patients' age, sex, suspected causative drugs, initial diagnosis of
      the prescribing physician, duration of drug-taking, diagnostic evaluations,
      treatment methods, and prognosis. RESULTS: Seventy-nine patients were enrolled.
      The mean age was 11.3+/-4.9 years (range, 4.0 months to 18.0 years), and 41
      patients (51.9%) were boys. The most common cause of DID was gastrointestinal
      medications in 45 patients (57.0%), followed by antipsychotics in 23 patients
      (29.1%). Eleven (24.4%) out of 45 patients with DID due to gastrointestinal
      medications had the initial diagnosis of upper respiratory infection, and seven
      (30.4%) out of 23 patients with DID due to antipsychotics had the initial
      diagnosis of non-psychotic diseases. Younger children received more diagnostic
      procedures and were more frequently admitted. A benzodiazepine (67.1%) was the
      most common single drug for treatment. CONCLUSION: Physicians should not only
      acknowledge DID in order to reduce unnecessary workup and admission, but also
      know that antiemetics and antipsychotics are common causes of DID. Therefore,
      physicians should try to avoid multidrug prescriptions in children.

PMID- 29026887
TI  - Single-dose intravenous sodium valproate (Depakine) versus dexamethasone for the
      treatment of acute migraine headache: a double-blind randomized clinical trial.
AB  - OBJECTIVE: Migraine headache is a chronic and disabling condition in adults. Some
      studies have investigated the efficacy of sodium valproate in the treatment of
      acute migraine, but the effectiveness and tolerability of intravenous valproate
      as abortive therapy remains unclear. This study aimed to evaluate the effects of
      sodium valproate and dexamethasone in the treatment of acute migraine. METHODS:
      We conducted a double-blind randomized clinical trial including 90 patients aged
      18 to 65 years with acute migraine headache but no aura. Patients were randomized
      to receive intravenous dexamethasone (8 mg) or sodium valproate (400 mg) diluted
      into 4 mL of normal saline. The primary outcome measure was pain relief after
      0.5, 1, 3, or 6 hours after administration. The secondary outcome criteria were
      the associated symptom recovery, rate of headache recurrence after 24 hours, and
      medication side effects. Pearson's chi square and the t-test were employed in the
      data analysis. RESULTS: Of the 90 patients, 80 were investigated. The percentage
      of headache improvement at 0.5 hours after treatment was 55% and 67.5% in the
      sodium valproate and dexamethasone groups, respectively. Before-treatment and 0.5
      hour after treatment pain severity visual analog scale scores were 9.05+/-0.90
      and 3.8+/-3.09 in the sodium valproate group and 8.92+/-0.79 and 3.10+/-2.73 in
      the dexamethasone group, respectively. There were no significant intergroup
      differences. CONCLUSION: This randomized clinical trial showed that the
      intravenous injection of sodium valproate 400 mg has similar effects to those of
      dexamethasone for improving acute migraine headache.

PMID- 29026888
TI  - Korean Shock Society septic shock registry: a preliminary report.
AB  - OBJECTIVE: To evaluate the clinical characteristics, therapeutic interventions,
      and outcomes of patients with septic shock admitted to the emergency department
      (ED). METHODS: This study was a preliminary, descriptive analysis of a
      prospective, multi-center, observational registry of the EDs of 10 hospitals
      participating in the Korean Shock Society. Patients aged 19 years or older who
      had a suspected or confirmed infection and evidence of refractory hypotension or
      hypoperfusion were included. RESULTS: A total of 468 patients were enrolled
      (median age, 71.3 years; male, 55.1%; refractory hypotension, 82.9%;
      hyperlactatemia without hypotension, 17.1%). Respiratory infection was the most
      common source of infection (31.0%). The median Sepsis-related Organ Failure
      Assessment score was 7.5. The sepsis bundle compliance was 91.2% for lactate
      measurement, 70.3% for blood culture, 68.4% for antibiotic administration, 80.3%
      for fluid resuscitation, 97.8% for vasopressor application, 68.0% for central
      venous pressure measurement, 22.0% for central venous oxygen saturation
      measurement, and 59.2% for repeated lactate measurement. Among patients who
      underwent interventions for source control (n=117, 25.1%), 43 (36.8%) received
      interventions within 12 hours of ED arrival. The in-hospital, 28-day, and 90-day
      mortality rates were 22.9%, 21.8%, and 27.1%, respectively. The median ED and
      hospital lengths of stay were 6.8 hours and 12 days, respectively. CONCLUSION:
      This preliminary report revealed a mortality of over 20% in patients with septic
      shock, which suggests that there are areas for improvement in terms of the
      quality of initial resuscitation and outcomes of septic shock patients in the ED.

PMID- 29026889
TI  - Study design of Real World Evidence for Treatment of Hyperkalemia in the
      Emergency Department (REVEAL-ED): a multicenter, prospective, observational
      study.
AB  - OBJECTIVE: Hyperkalemia affects up to 10% of hospitalized patients and, if left
      untreated, can lead to serious cardiac arrhythmias or death. Although
      hyperkalemia is frequently encountered in the emergency department (ED), and is
      potentially life-threatening, standard of care for the treatment is poorly
      defined, with little supporting evidence. The main objectives of this
      observational study are to define the overall burden of hyperkalemia in the ED
      setting, describe its causes, the variability in treatment patterns and
      characterize the effectiveness and safety of ED standard of care therapies used
      in the United States. METHODS: This is an observational study evaluating the
      management of hyperkalemia in the ED. Two hundred and three patients who
      presented to the ED with a potassium value >=5.5 mmol/L were enrolled in the
      study at 14 sites across the United States. Patients were treated per standard of
      care practices at the discretion of the patient's physician. In patients who
      received a treatment for hyperkalemia, blood samples were drawn at pre-specified
      time points and serum potassium values were recorded. The change in potassium
      over 4 hours and the adverse events after standard of care treatment were
      analyzed. RESULTS AND CONCLUSION: This article describes the background,
      rationale, study design, and methodology of the REVEAL-ED (Real World Evidence
      for Treatment of Hyperkalemia in the Emergency Department) trial, a multicenter,
      prospective, observational study evaluating contemporary management of patients
      admitted to the ED with hyperkalemia.

PMID- 29026890
TI  - Changes in histopathology and tumor necrosis factor-alpha levels in the hearts of
      rats following asphyxial cardiac arrest.
AB  - OBJECTIVE: Post cardiac arrest (CA) syndrome is associated with a low survival
      rate in patients who initially have return of spontaneous circulation (ROSC)
      after CA. The aim of this study was to examine the histopathology and
      inflammatory response in the heart during the post CA syndrome. METHODS: We
      induced asphyxial CA in male Sprague-Dawley rats and determined the survival rate
      of these rats during the post resuscitation phase. RESULTS: Survival of the rats
      decreased after CA: 66.7% at 6 hours, 36.7% at 1 day, and 6.7% at 2 days after
      ROSC following CA. The rats were sacrificed at 6 hours, 12 hours, 1 day, and 2
      days after ROSC, and their heart tissues were examined. Histopathological scores
      increased at 12 hours post CA and afterwards, histopathological changes were not
      significant. In addition, levels of tumor necrosis factor-alpha immunoreactivity
      gradually increased after CA. CONCLUSION: The survival rate of rats 2 days post
      CA was very low, even though histopathological and inflammatory changes in the
      heart were not pronounced in the early stage following CA.

PMID- 29026891
TI  - Effect of emergency medical service use on time interval from symptom onset to
      hospital admission for definitive care among patients with intracerebral
      hemorrhage: a multicenter observational study.
AB  - OBJECTIVE: This study evaluated whether emergency medical service (EMS) use was
      associated with early arrival and admission for definitive care among
      intracerebral hemorrhage (ICH) patients. METHODS: Patients with ICH were enrolled
      from 29 hospitals between November 2007 and December 2012, excluding those
      patients with subarachnoid hemorrhage, traumatic ICH, and missing information.
      The patients were divided into four groups based on visit type to the definitive
      hospital emergency department (ED): direct visit by EMS (EMS-direct), direct
      visit without EMS (non-EMS-direct), transferred from a primary hospital by EMS
      (EMS-transfer), and transferred from a primary hospital without EMS (non-EMS
      transfer). The outcomes were the proportions of participants within early (<1 hr)
      definitive hospital ED arrival from symptom onset (pS2ED) and those within early
      (<4 hr) admission from symptom onset (pS2AD). Adjusted odds ratios were
      calculated to determine the association between EMS use and outcomes with and
      without inter-hospital transfer. RESULTS: A total of 6,564 patients were
      enrolled. The adjusted odds ratios (95% confidence intervals) for pS2ED were
      22.95 (17.73-29.72), 1.11 (0.67-1.84), and 7.95 (6.04-10.46) and those for pS2AD
      were 5.56 (4.70-6.56), 0.96 (0.71-1.30), and 2.35 (1.94-2.84) for the EMS-direct,
      EMS-transfer, and non-EMS-direct groups compared with the non-EMS-transfer group,
      respectively. Through the interaction model, EMS use was significantly associated
      with early arrival and admission among direct visiting patients but not with
      transferred patients. CONCLUSION: EMS use was significantly associated with
      shorter time intervals from symptom onset to arrival and admission at a
      definitive care hospital. However, the effect disappeared when patients were
      transferred from a primary hospital.

PMID- 29026892
TI  - Prompt diagnosis of ST-elevation myocardial infarction with papillary muscle
      rupture by point-of-care ultrasound in the emergency department.
AB  - A previously healthy 61-year-old man presented to the emergency department with
      chest pain and dyspnoea for 6 hours. Examination revealed distress with an apical
      pansystolic murmur. Initial electrocardiogram showed sinus tachycardia and ST
      elevation in leads II, III, and aVF compatible with an inferior ST-elevation
      myocardial infarction. Point-of-care echocardiography in the emergency department
      showed a flail anterior mitral leaflet and severe mitral regurgitation, leading
      to a provisional diagnosis of papillary muscle rupture. Emergency cardiac
      catheterization showed 100%, 80%, and 70% occlusion of the middle right coronary,
      left anterior descending, and left circumflex arteries, respectively. An
      emergency triple vessel coronary artery bypass grafting and mitral valve
      replacement was performed. Posteromedial papillary muscle rupture resulting in
      mitral regurgitation was confirmed intraoperatively. The patient recovered
      uneventfully. In the absence of primary percutaneous coronary intervention,
      thrombolysis decisions should be made with extreme caution if mechanical
      complications of ST-elevation myocardial infarction are suspected.

PMID- 29026893
TI  - Descending necrotizing mediastinitis after a trigger point injection.
AB  - Descending necrotizing mediastinitis (DNM) is a rare form of mediastinal
      infection. Most cases are associated with esophageal rupture. DNM after a trigger
      point injection in the upper trapezius has not been described previously. We
      present a case of DNM after a trigger point injection in the upper trapezius. A
      70-year-old man visited the emergency department with chest discomfort and fever
      after a trigger point injection in the left upper trapezius. Chest computed
      tomography showed evidence of DNM, and antibiotic therapy was immediately
      administered intravenously. Because of the risk of sudden death, poor prognosis
      due to underlying disease, and his age, he declined surgical treatment and died
      of septic shock. Although trigger point injections are generally considered safe,
      caution should be used in patients with an underlying disease or in the elderly.
      Early diagnosis, broad-spectrum antibiotics, and aggressive surgical management
      are essential to improve the prognosis.

PMID- 29026894
TI  - Hounsfield units in pseudo subarachnoid hemorrhage: worth looking for.

PMID- 29026895
TI  - Non-radiographic methods of measuring global sagittal balance: a systematic
      review.
AB  - BACKGROUND: Global sagittal balance, describing the vertical alignment of the
      spine, is an important factor in the non-operative and operative management of
      back pain. However, the typical gold standard method of assessment, radiography,
      requires exposure to radiation and increased cost, making it unsuitable for
      repeated use. Non-radiologic methods of assessment are available, but their
      reliability and validity in the current literature have not been systematically
      assessed. Therefore, the aim of this systematic review was to synthesise and
      evaluate the reliability and validity of non-radiographic methods of assessing
      global sagittal balance. METHODS: Five electronic databases were searched and
      methodology evaluated by two independent reviewers using the13-item, reliability
      and validity, Brink and Louw critical appraisal tool. RESULTS: Fourteen articles
      describing six methodologies were identified from 3940 records. The six non
      radiographic methodologies were biophotogrammetry, plumbline, surface topography,
      infra-red motion analysis, spinal mouse and ultrasound. Construct validity was
      evaluated for surface topography (R = 0.49 and R = 0.68, p < 0.001), infra-red
      motion-analysis (ICC = 0.81) and plumbline testing (ICC = 0.83). Reliability
      ranged from moderate (ICC = 0.67) for spinal mouse to very high for surface
      topography (Cronbach alpha = 0.985). Measures of agreement ranged from 0.9 mm
      (plumbline) to 22.94 mm (infra-red motion-analysis). Variability in study
      populations, reporting parameters and statistics prevented a meta-analysis.
      CONCLUSIONS: The reliability and validity of the non-radiographic methods of
      measuring global sagittal balance was reported within 14 identified articles.
      Based on this limited evidence, non-radiographic methods appear to have moderate
      to very high reliability and limited to three methodologies, moderate to high
      validity. The overall quality and methodological approaches of the included
      articles were highly variable. Further research should focus on the validity of
      non-radiographic methods with a greater adherence to reporting actual and
      clinically relevant measures of agreement.

PMID- 29026896
TI  - Tau and Pet/Mri Imaging Biomarkers for Detecting and Diagnosing Early Dementia.
AB  - Specific objective of this project is to quantify the neuropathological tau
      depositions in brain regions and to investigate primary age-related tau pathology
      and associations with amyloid and glucose-metabolism, neurocognitive tests and
      MRI metrics. Preliminary results demonstrated higher temporal deposition
      especially in the hippocampus and the inferior temporal regions compared to mean
      cortical deposition. Quantitative Braak stage-based regional analyses found
      highest tau deposition in the Braak stage II in the preclinical samples. There
      was significant age related higher tau deposition in temporal cortex, while non
      significant correlation in mean cortical region. Significant correlations were
      found between tau deposition and memory as well as executive function scores,
      especially from middle and inferior temporal cortex; and significant correlations
      between tau and MRI metrics including diffusion, perfusion, functional and
      structural connectivities. Our results confirm current notion of this new tau
      tracer for reliably and consistently labeling and quantifying in vivo human
      taupathy in early dementia.

PMID- 29026897
TI  - cis-Thioindigo (TI) - a new ligand with accessible radical anion and dianion
      states. Strong magnetic coupling in the {[TI-(MU2-O),(MU-O)]Cp*Cr}2 dimers.
AB  - Reaction of decamethylchromocene (Cp*2Cr) with thioindigo (TI) yields a
      coordination complex {[TI-(MU2-O), (MU-O)]Cp*Cr}2.C6H14 (1) in which one Cp*
      ligand in Cp*2Cr is substituted by TI. TI adopts cis-conformation in 1 allowing
      the coordination of both carbonyl groups to chromium. Additionally, one oxygen
      atom of TI becomes a MU2-bridge for two chromium atoms to form {[TI-(MU2-O), (MU
      O)]Cp*Cr}2 dimers with a CrCr distance of 3.12 A. According to magnetic data,
      diamagnetic TI2- dianions and two Cr3+ atoms with a high S = 3/2 spin state are
      present in a dimer allowing strong antiferromagnetic coupling between two Cr3+
      spins with an exchange interaction of -35.4 K and the decrease of molar magnetic
      susceptibility below 140 K. Paramagnetic TI- radical anions with the S = 1/2 spin
      state have also been obtained and studied in crystalline
      {cryptand[2,2,2](Na+)}(TI-) (2) salt showing that both radical anion and dianion
      states are accessible for TI.

PMID- 29026898
TI  - Controlling azobenzene photoswitching through combined ortho-fluorination and 
      amination.
AB  - We present a series of visible-light-absorbing azobenzene photoswitches with cis
      lifetimes ranging from one second to three days. We combine ortho-fluorination to
      control the cis-lifetimes, and ortho-amination to boost the visible-light
      absorption. The synthesis is accomplished by selectively replacing one or more
      ortho-fluorines with amines in the ortho-fluoroazobenzene precursors.

PMID- 29026899
TI  - Few-layered metallic 1T-MoS2/TiO2 with exposed (001) facets: two-dimensional
      nanocomposites for enhanced photocatalytic activities.
AB  - Titanium dioxide (TiO2) with exposed (001) facets (TiO2(001)) has attractive
      photocatalytic properties. However, the high recombination rate of the photo
      excited charge carriers on this surface often limits its application. Here, we
      report that a few-layered 1T-MoS2 coating on TiO2(001) nanosheets (abbreviated as
      MST) can be a promising candidate that overcomes some of the challenges of
      TiO2(001). Computational and experimental results demonstrate that MST as a
      photocatalyst exhibits a significantly low-charge recombination rate as well as
      excellent long-term durability. The synthesized MST 2D nanocomposites show a
      31.9% increase in photocatalytic activity for hydrogen (H2) production relative
      to the counterpart TiO2(001). MST offers a new route for further improvement of
      the photocatalytic activity of TiO2 with exposed high energy facets.

PMID- 29026900
TI  - A series of sulfonic acid functionalized mixed-linker DUT-4 analogues: synthesis,
      gas sorption properties and catalytic performance.
AB  - In this work, we present the successful synthesis of a series of sulfonic acid
      functionalized mixed-linker metal-organic frameworks (MOFs) having the DUT-4
      topology by using different ratios of 2,6-naphthalenedicarboxylic acid (H2-NDC)
      and 4,8-disulfonaphthalene-2,6-dicarboxylic acid (H2-NDC-2SO3H) in one-pot
      reactions. The obtained materials were fully characterized and their CO2
      adsorption properties at low and high pressures were studied and compared with
      those of the pristine DUT-4 material. Generally, the CO2 adsorption capacities
      range from 3.28 and 1.36 mmol g-1 for DUT-4 to 1.54 and 0.78 mmol g-1 for DUT-4
      SO3H (50) up to 1 bar at 273 K and 303 K, respectively. Computational
      calculations corroborated the structural changes of the material in function of
      the loading of sulfonic acid groups. Furthermore, due to the strong Bronsted acid
      character, the resulting sulfonic acid based MOF material was evaluated as a
      catalyst for the ring opening of styrene oxide with methanol as a nucleophile
      under mild conditions, showing almost full conversion (99%) after 5 hours of
      reaction. A hot filtration experiment demonstrated that the catalysis occurred
      heterogeneously and the catalyst could be recovered and reused for multiple runs
      without significant loss in activity and crystallinity.

PMID- 29026901
TI  - Dietary iron loading negatively affects liver mitochondrial function.
AB  - Iron is an essential co-factor for several metabolic processes, including
      mitochondrial respiration, and mitochondria are the major sites of iron
      utilization. Cellular iron homeostasis must be tightly regulated, as
      intracellular iron deficiency can lead to insufficient energy production, whereas
      iron overload triggers ROS (reactive oxygen species) formation via the Fenton
      reaction. So far little is known on how iron imbalances affect mitochondrial
      function in vivo and the impact of the genotype on that, we studied the effects
      of dietary iron loading on mitochondrial respiratory capacity in liver by
      comparing two genetically divergent mouse strains, namely C57BL/6N and FVB mice.
      Both mouse strains differed in their basal iron levels and their metabolic
      responses to iron loading as determined by expression of iron trafficking
      proteins (ferritin was increased in livers of animals receiving high iron diet)
      as well as tissue iron content (2-fold increase, FVB p = 0.0013; C57BL/6N p =
      0.0022). Dietary iron exposure caused a significant impairment of mitochondrial
      oxidative phosphorylation, especially regarding OXPHOS capacity (FVB p = 0.0006;
      C57BL/6N p = 0.0087) and S-ETS capacity (FVB p = 0.0281; C57BL/6N p = 0.0159).
      These effects were more pronounced in C57BL/6N than in FVB mice and were
      paralleled by an iron mediated induction of oxidative stress in mitochondria. The
      increased susceptibility of C57BL6/N mice to iron loading may be due to reduced
      expression of anti-oxidant defense mechanisms and altered iron trafficking upon
      dietary challenge pointing to a role of genetic modifiers for cellular and
      mitochondrial iron trafficking. Finally, iron-mediated induction of mitochondrial
      oxidative stress and reduction of oxidative phosphorylation may underlie fatigue
      in subjects with iron loading diseases.

PMID- 29026903
TI  - The effect of cognitive demand on performance of an executive function task
      following wild blueberry supplementation in 7 to 10 years old children.
AB  - The cognitive benefits of acute flavonoid interventions have been well
      documented, however, research to date has found that, depending on developmental
      stage, these benefits manifest themselves in different cognitive domains. It is
      argued that the lack of global cognitive effects following flavonoid intervention
      may be a result of insufficient task sensitivity for those domains where no
      benefits are found. In children, executive function is a cognitive domain which
      has shown little apparent benefit following flavonoid intervention. Here, we
      describe a Modified Attention Network Task (MANT) designed to vary levels of
      cognitive demand across trials in order to investigate whether flavonoid related
      benefits can be shown for executive function when task sensitivity is carefully
      manipulated. Twenty-one children were recruited to a double blind cross-over
      study consuming 30 g freeze dried blueberry powder (WBB) or placebo before being
      tested at 3 hours. Performance in the WBB condition was found to be significantly
      faster in comparison to placebo particularly on more cognitively demanding
      incongruent and high load trials. Trials in which a visual cue alerted
      participants to the imminent appearance of the target also showed better
      performance following WBB administration. We conclude that WBB administration can
      enhance executive function during demanding elements of a task, but that the
      complexity and demand of the task as a whole may be equally important to
      performance.

PMID- 29026902
TI  - Exploring the origins of selectivity in soluble epoxide hydrolase from Bacillus
      megaterium.
AB  - Epoxide hydrolase (EH) enzymes catalyze the hydration of racemic epoxides to
      yield their corresponding vicinal diols. These enzymes present different enantio-
      and regioselectivity depending upon either the substrate structure or the
      substitution pattern of the epoxide ring. In this study, we computationally
      investigate the Bacillus megaterium epoxide hydrolase (BmEH)-mediated hydrolysis
      of racemic styrene oxide (rac-SO) and its para-nitro styrene oxide (rac-p-NSO)
      derivative using density functional theory (DFT) and an active site cluster model
      consisting of 195 and 197 atoms, respectively. Full reaction mechanisms for
      epoxide ring opening were evaluated considering the attack at both oxirane
      carbons and considering two possible orientations of the substrate at the BmEH
      active site. Our results indicate that for both SO and p-NSO substrates the BmEH
      enantio- and regioselectivity is opposite to the inherent (R)-BmEH selectivity,
      the attack at the benzylic position (C1) of the (S)-enantiomer being the most
      favoured chemical outcome.

PMID- 29026904
TI  - One-step functionalization of magnetic nanoparticles with 4-mercaptophenylboronic
      acid for a highly efficient analysis of N-glycopeptides.
AB  - A very simple and amazing approach was proposed to synthesize MPBA functionalized
      magnetic nanoparticles via the interaction between Fe and SH, and the as-prepared
      nanoparticles were successfully applied for the efficient analysis of
      glycopeptides in complex bio-samples with sensitivity and selectivity.

PMID- 29026905
TI  - Imaging Abeta(1-42) fibril elongation reveals strongly polarised growth and
      growth incompetent states.
AB  - The major hallmark of Alzheimer's disease is the deposition of plaques of amyloid
      fibrils formed from amyloid-beta (Abeta) peptides. Kinetic studies have
      contributed significantly towards a mechanistic understanding of amyloid fibril
      self-assembly, however dynamic features of the aggregation process cannot be
      captured using ensemble methods. Here we present an assay for imaging Abeta42
      aggregation dynamics at the single fibril level, allowing for the quantitative
      extraction of concentration and temperature dependent kinetic parameters. From
      direct observation of elongation using TIRF and super-resolution optical
      microscopy, we find that Abeta42 fibril growth is strongly polarized, with fast
      and slow growing ends arising from different elongation rates, but also from a
      growth incompetent state, which dominates the process at the slow growing end.
      Our findings reveal the surprising complexity of the Abeta42 fibril elongation
      reaction at the microscopic level.

PMID- 29026906
TI  - Recognition-driven chemical labeling of endogenous proteins in multi-molecular
      crowding in live cells.
AB  - Endogenous protein labeling is one of the most invaluable methods for studying
      the bona fide functions of proteins in live cells. However, multi-molecular
      crowding conditions, such as those that occur in live cells, hamper the highly
      selective chemical labeling of a protein of interest (POI). We herein describe
      how the efficient coupling of molecular recognition with a chemical reaction is
      crucial for selective protein labeling. Recognition-driven protein labeling is
      carried out by a synthetic labeling reagent containing a protein (recognition)
      ligand, a reporter tag, and a reactive moiety. The molecular recognition of a POI
      can be used to greatly enhance the reaction kinetics and protein selectivity,
      even under live cell conditions. In this review, we also briefly discuss how such
      selective chemical labeling of an endogenous protein can have a variety of
      applications at the interface of chemistry and biology.

PMID- 29026907
TI  - A two-dimensional layered CdS/C2N heterostructure for visible-light-driven
      photocatalysis.
AB  - In this work, we employ hybrid density functional theory calculations to design a
      two-dimensional layered CdS/C2N heterostructure for visible light photocatalytic
      water splitting to produce hydrogen. The calculation results show that the
      conduction band minimum (CBM) and the valence band maximum (VBM) of C2N
      monolayers are lower than those of CdS nanosheets by about 0.76 eV and 0.44 eV,
      respectively. The type-II band alignment, density of states, Bader charge
      analysis, and charge density difference of the CdS/C2N heterostructure indicate
      that the photogenerated electrons migrate from the CdS monolayer to the C2N
      monolayer, favoring the separation and transfer of photogenerated charge
      carriers, which restrains the recombination of photogenerated carriers and
      enhances the photocatalytic efficiency. The calculated band gap and optical
      absorption spectra reveal that the two-dimensional layered CdS/C2N
      heterostructure may be a potential photocatalyst for photo-electrochemical water
      splitting because of its appropriate band gap and excellent visible light
      absorption behavior. Moreover, the electronic and optical properties of the
      CdS/C2N heterostructure can be effectively modulated by the strain. These
      findings suggest that the C2N sheets are a promising candidate as metal-free co
      catalysts for CdS photocatalysts, and also provide valuable information for
      experimentalists to design highly active and efficient visible light
      photocatalysts for water splitting.

PMID- 29026908
TI  - Chiral N,N'-dioxide/Sc(OTf)3 complex-catalyzed asymmetric dearomatization of beta
      naphthols.
AB  - An efficient N,N'-dioxide-scandium(iii) complex catalytic system has been
      developed for the asymmetric dearomatization of beta-naphthols through conjugate
      addition to alkynones. A variety of Z-predominated beta-naphthalenone compounds
      were obtained in moderate to high yields with excellent enantioselectivities (up
      to 98% ee). Moreover, a possible transition state was proposed to explain the
      origin of the stereoselectivity.

PMID- 29026915
TI  - ?

PMID- 29026916
TI  - ?

PMID- 29026914
TI  - Author Correction: Emotional faces influence evaluation of natural and
      transformed food.
AB  - This article unfortunately contained two mistakes.

PMID- 29026917
TI  - [Fractures of the lower extremities in childhood : Part 2: lower leg and ankle
      fractures].
AB  - The treatment of pediatric patients in trauma surgery is a special situation in
      every aspect. For deciding on the correct treatment of fractures of the lower leg
      and ankle joint, various parameters, such as residual growth rate, skeletal age
      and height of the patient are decisive. The differences between fractures in
      children and adolescents are the open epiphyseal plate and the resulting residual
      growth. The bones of young children have a higher healing tendency and a greater
      potential for correction than in adolescents. Especially in the lower leg and the
      ankle joint, the potential for correction is decisive for the healing of
      fractures and for possible development of growth disorders. The limits of
      tolerance concerning axial malalignments and the expected spontaneous potential
      for correction must play an essential role for further treatment with
      conservative or operative therapy. This article deals with the special features
      of pediatric fractures of the lower leg and ankle joint.

PMID- 29026918
TI  - Correction to: 4-Chloro-3-nitro-N-butylbenzenesulfonamide acts on KV3.1 channels
      by an open-channel blocker mechanism.
AB  - Unfortunately, grey trace on Figure 2c was missing in the original publication of
      the article.

PMID- 29026919
TI  - Correction to: Transcriptome profiling of fully open flowers in a frost-tolerant
      almond genotype in response to freezing stress.
AB  - In the original publication of the article, the affiliation of the third author
      has been incorrectly published as University of Yazd. However, the correct
      affiliation is Yazd University.

PMID- 29026920
TI  - Immunotherapy as an Option for Cancer Treatment.
AB  - The progress in melanoma immunotherapy highlights the importance of immunotherapy
      for cancer treatment. Although the concept of immunotherapy emerged in the
      beginning of the twentieth century, the end of the century signaled the start of
      modern immunotherapy, which has recently allowed a staggering progress in the
      field of cancer immunotherapy. Currently, there is a wide variety of
      immunotherapeutic approaches and critical improvements are continually being
      made. Among different immunotherapeutic strategies, therapies based on the
      blockade of immune checkpoint molecules have shown unparalleled efficacy in late
      stage cancer patients. Pre-clinical research using ex vivo and in vivo approaches
      demonstrates the promise of numerous novel strategies for the immunotherapy of
      cancer.

PMID- 29026922
TI  - Erratum to: Innovative technology shows impact of glycaemic control on peripheral
      retinal vessels in adolescents with type 1 diabetes.

PMID- 29026923
TI  - Nonhuman Primate Models for Studies of AIDS Virus Persistence During Suppressive
      Combination Antiretroviral Therapy.
AB  - Nonhuman primate (NHP) models of AIDS represent a potentially powerful component
      of the effort to understand in vivo sources of AIDS virus that persist in the
      setting of suppressive combination antiretroviral therapy (cART) and to develop
      and evaluate novel strategies for more definitive treatment of HIV infection
      (i.e., viral eradication "cure", or sustained off-cART remission). Multiple
      different NHP models are available, each characterized by a particular NHP
      species, infecting virus, and cART regimen, and each with a distinct capacity to
      recapitulate different aspects of HIV infection. Given these different biological
      characteristics, and their associated strengths and limitations, different models
      may be preferred to address different questions pertaining to virus persistence
      and cure research, or to evaluate different candidate intervention approaches.
      Recent developments in improved cART regimens for use in NHPs, new viruses, a
      wider array of sensitive virologic assay approaches, and a better understanding
      of pathogenesis should allow even greater contributions from NHP models to this
      important area of HIV research in the future.

PMID- 29026924
TI  - Gene Regulation, Two Component Regulatory Systems, and Adaptive Responses in
      Treponema Denticola.
AB  - The oral microbiome consists of a remarkably diverse group of 500-700 bacterial
      species. The microbial etiology of periodontal disease is similarly complex. Of
      the ~400 bacterial species identified in subgingival plaque, at least 50 belong
      to the genus Treponema. As periodontal disease develops and progresses, T.
      denticola transitions from a low to high abundance species in the subgingival
      crevice. Changes in the overall composition of the bacterial population trigger
      significant changes in the local physical, immunological and physiochemical
      conditions. For T. denticola to thrive in periodontal pockets, it must be nimble
      and adapt to rapidly changing environmental conditions. The purpose of this
      chapter is to review the current understanding of the molecular basis of these
      essential adaptive responses, with a focus on the role of two component
      regulatory systems with global regulatory potential.

PMID- 29026925
TI  - ER Protein Quality Control and the Unfolded Protein Response in the Heart.
AB  - Cardiac myocytes are the cells responsible for the robust ability of the heart to
      pump blood throughout the circulatory system. Cardiac myocytes grow in response
      to a variety of physiological and pathological conditions; this growth challenges
      endoplasmic reticulum-protein quality control (ER-PQC), a major feature of which
      includes the unfolded protein response (UPR). ER-PQC and the UPR in cardiac
      myocytes growing under physiological conditions, including normal development,
      exercise, and pregnancy, are sufficient to support hypertrophic growth of each
      cardiac myocyte. However, the ER-PQC and UPR are insufficient to respond to the
      challenge of cardiac myocyte growth under pathological conditions, including
      myocardial infarction and heart failure. In part, this insufficiency is due to a
      continual decline in the expression levels of important adaptive UPR components
      as a function of age and during myocardial pathology. This chapter will discuss
      the physiological and pathological conditions unique to the heart that involves
      ER-PQC, and whether the UPR is adaptive or maladaptive under these circumstances.

PMID- 29026921
TI  - Role of gut microbiota in aging-related health decline: insights from
      invertebrate models.
AB  - Studies in mammals, including humans, have reported age-related changes in
      microbiota dynamics. A major challenge, however, is to dissect the cause and
      effect relationships involved. Invertebrate model organisms such as the fruit fly
      Drosophila and the nematode Caenorhabditis elegans have been invaluable in
      studies of the biological mechanisms of aging. Indeed, studies in flies and worms
      have resulted in the identification of a number of interventions that can slow
      aging and prolong life span. In this review, we discuss recent work using
      invertebrate models to provide insight into the interplay between microbiota
      dynamics, intestinal homeostasis during aging and life span determination. An
      emerging theme from these studies is that the microbiota contributes to cellular
      and physiological changes in the aging intestine and, in some cases, age-related
      shifts in microbiota dynamics can drive health decline in aged animals.

PMID- 29026926
TI  - Erratum to: Nitrate and Nitrogen Oxides: Sources, Health Effects and Their
      Remediation.

PMID- 29026927
TI  - Diagnostics and early treatment in prehospital and emergency-room phase in
      suspicious pelvic ring fractures.
AB  - BACKGROUND: Testing for mechanical stability in pelvic ring fractures is
      advocated for the initial assessment and management of pelvic ring fractures. A
      survey among trauma surgeons showed that 91% agree with this recommendation. The
      aim of the present study was to describe the actual workup of patients with a
      high risk for unstable pelvic fractures in daily routine. METHODS: We performed a
      prospective multicenter observational study on patients admitted to the emergency
      room with suspected pelvic ring fractures. Data were collected anonymously via a
      standardized case report. RESULTS: A total of 254 patients with suspected pelvic
      injuries from 12 different trauma centers were included in this study. In 95 out
      of 254 cases a per definition unstable pelvic fracture could be confirmed; 46
      type B and 49 type C fractures was confirmed. Mechanical stability examination
      was carried out in 61% and revealed a sensitivity of 31.6% and a specificity of
      92.2%. 11.5% (18 patients) actually showed a mechanical instability (6 B# 12 C#).
      Regardless, 166 patients (65.4%) received noninvasive external stabilization
      ahead of diagnostic imaging, as a result of clinical judgment. 72% (24*) showed
      signs of significant bleeding in the subsequent CT scans. 33 pelvic ring
      fractures (type B or C) had no prehospital stabilization. CONCLUSION: Testing of
      mechanical stability of the pelvic ring was carried out less often and with lower
      consequences for the actual management than expected. It seems worthwhile to
      rather put on a pelvic binder at earliest occasion based on trauma mechanism or
      clinical findings to reduce the risk of serious pelvic bleeding.

PMID- 29026928
TI  - [Current treatment concepts in intracerebral hemorrhage].
AB  - BACKGROUND AND OBJECTIVE: In recent years, various important studies
      investigating the management of intracerebral hemorrhage (ICH) have been
      published. However, these have not entered guideline recommendations yet.
      Therefore, essential results are summarized here and the findings are integrated
      into current treatment concepts. MATERIALS AND METHODS: Based on a dedicated
      literature review and the authors' experience, up-to-date and high-quality
      investigations were identified. RESULTS AND DISCUSSION: Randomized data and meta
      analyses provide evidence that aggressive blood-pressure reduction (targeting a
      systolic blood pressure <140 mm Hg) appears safe and reduces hematoma
      enlargement. ICH associated with intake of vitamin K antagonists should be
      reversed immediately using prothrombin complex concentrates (PCC) and vitamin K,
      targeting at least international normalized ratio levels below 1.3. For
      dabigatran-related ICH, an antidote (idarucizumab) is available for reversal, but
      in ICH under the use of factor Xa inhibitors evidence is poor. However, reversal
      should be carried out using high-dosed PCC (50 IU/kg PCC). Routine hematoma
      evacuation surgery cannot be advocated, yet new minimally invasive strategies
      provide promising results. In patients with acute occlusive hydrocephalus, an
      external ventricular drain should be placed and utilizing intraventricular lysis
      appears safe, reduces mortality, and is associated with improved functional
      outcome. Adding lumbar drainage to this treatment strategy may reduce permanent
      shunt dependency. The sum of treatment measures and specialized care at high
      volume centers improves outcome in patients with ICH.

PMID- 29026929
TI  - The outcome of proximal fifth metatarsal fractures: redefining treatment
      strategies.
AB  - BACKGROUND: To optimize the treatment strategy and reduce treatment costs of
      proximal fifth metatarsal fractures, clinical and patient-reported outcome, and
      its determinants were addressed. METHODS: A retrospective adult cohort study
      including 152 proximal fifth metatarsal fractures: 121 nonoperatively and 31
      operatively treated. In the operative group, 21 were zone 1 and 10 zone 2
      fractures. Median follow-up was 37.5 (IQR 20.8-52.3) months with a minimal follow
      up of 6 months. Twenty-three demographic, fracture, and treatment characteristics
      were assessed as well as the healthcare costs. Outcome was assessed using the
      patient files, anterior-posterior and oblique X-rays, foot function index (FFI),
      visual analog score (VAS), and SF-36 questionnaires. RESULTS: The median FFI,
      physical SF-36, and VAS scores did not significantly differ between
      nonoperatively and operatively treated patients. The FFI and physical SF-36 were
      predominantly affected by a history of mobility impairment and pre-existent
      cardiovascular diseases, whereas mental SF-36 correlated significantly with
      higher ASA-score. Overall complication rate was 5.9% (4.1 vs. 12.9%; p = 0.065,
      nonoperative vs. operative, respectively). Nonunion was recorded in only one
      (nonoperatively) treated patient. The total healthcare costs for operative
      treatment were 4.2 times higher compared to nonoperative treatment (?1960 vs.
      ?463 per patient, respectively). CONCLUSION: Overall, the clinical and patient
      reported outcome was good. The foot function and quality of life were mainly
      affected by comorbidity, rather than fracture and treatment-related variables.
      Although nonoperatively treated patients indicated decreased mental quality of
      life, our study indicates that proximal fifth metatarsal fractures can safely be
      treated nonoperatively without the risk of nonunion, with fewer complications and
      lower healthcare costs. LEVEL OF EVIDENCE: 3.

PMID- 29026930
TI  - [Burnout-a call for action].
AB  - BACKGROUND: Burnout is an emerging topic and has recently been the subject of a
      position paper of the US American Society of Critical Care Medicine. OBJECTIVES:
      To give an overview over prevalence, causes, and relevance of burnout in
      intensive care unit (ICU) clinicians and point to potential prevention strategies
      MATERIALS AND METHODS: Narrative review. RESULTS AND CONCLUSION: Burnout is a job
      related state which results from long-lasting, permanent work overload when short
      spells of recreation, for instance during the weekend, are not effective to
      reduce exhaustion, vegetative symptoms, loss of efficiency, and
      depersonalization. Burnout may be due to (1) work-related factors, such as
      unmanageable workload and lack of appreciation by superiors and (2) personal
      factors, such as overly high demand and commitment. Surveys from France and
      Switzerland suggest that approximately one third to one half of ICU clinicians
      are affected. Large studies among hospital nurses show an increase in burnout.
      Burnout impairs patient safety and satisfaction, increases clinicians' intent to
      quit, and staff turnover. CONCLUSIONS: Burnout is associated with a poor work
      environment. Burnout prevention or reduction is an important task which demands a
      multidimensional approach. The goal should be to improve the work environment,
      achieve good team collaboration, psychological safety, and inclusive leadership.

PMID- 29026931
TI  - Imaging Patterns of Rhino-Orbital-Cerebral Mucormycosis in Immunocompromised
      Patients : When to Suspect Complicated Mucormycosis.
AB  - PURPOSE: The aim of this study was to describe radiological imaging findings of a
      complicated sinusitis, which should raise the suspicion of rhino-orbital-cerebral
      mucormycosis as being the underlying cause. METHODS: In this retrospective
      analysis, we describe the cases and imaging findings of 8 patients with proven
      mucormycosis. These patients presented mostly with new facial or orbital swelling
      and were referred for imaging to our institution. Magnetic resonance imaging and
      computed tomography images were classified as abnormal or normal with respect to
      orbital, paranasal and cerebral signal results. Special emphasis was placed on
      the distribution of the signal abnormalities regarding involvement of the skull
      base and the cavernous sinus. RESULTS: Out of a pool of 43 patients with
      colonization or proven Mucorales infection at different sites of the body, we
      identified 8 patients with infiltration of the midface and skull base.
      Unexpectedly seven out of the eight patients with abnormal findings of the
      paranasal sinuses and the adjacent tissues showed no bony sinus wall destruction.
      Of the eight patients seven showed inflammatory changes involving the
      infratemporal fossa and facial/periorbital tissues, three of the eight patients
      suffered from fungal invasion of the cavernous sinus and the carotid artery and
      one of the eight patients had a local infection of the hard palate only.
      CONCLUSION: Imaging findings of inflammatory tissue infiltration adjacent to the
      paranasal sinuses with possible extension into the pterygopalatine fossa,
      infratemporal fossa and orbit or the cavernous sinus should raise the suspicion
      of a mucormycosis, especially in immunocompromised patients.

PMID- 29026932
TI  - [PROtocol-based MObilizaTION on intensive care units : Design of a cluster
      randomized pilot study].
AB  - BACKGROUND: Despite convincing evidence for early mobilization of patients on
      intensive care units (ICU), implementation in practice is limited. Protocols for
      early mobilization, including in- and exclusion criteria, assessments, safety
      criteria, and step schemes may increase the rate of implementation and
      mobilization. HYPOTHESIS: Patients (population) on ICUs with a protocol for early
      mobilization (intervention), compared to patients on ICUs without protocol
      (control), will be more frequently mobilized (outcome). METHODS: A multicenter,
      stepped-wedge, cluster-randomized pilot study is presented. Five ICUs will
      receive an adapted, interprofessional protocol for early mobilization in
      randomized order. Before and after implementation, mobilization of ICU patients
      will be evaluated by randomized monthly one-day point prevalence surveys. Primary
      outcome is the percentage of patients mobilized out of bed, operationalized as a
      score of >=3 on the ICU Mobility Scale. Secondary outcome parameters will be
      presence and/or length of mechanical ventilation, delirium, stay on ICU and in
      hospital, barriers to early mobilization, adverse events, and process parameters
      as identified barriers, used strategies, and adaptions to local conditions.
      EXPECTED RESULTS: Exploratory evaluation of study feasibility and estimation of
      effect sizes as the basis for a future explanatory study.

PMID- 29026934
TI  - Early oseltamivir therapy improves the outcome in critically ill patients with
      influenza: a propensity analysis.

PMID- 29026933
TI  - Measurement properties of the most commonly used Foot- and Ankle-Specific
      Questionnaires: the FFI, FAOS and FAAM. A systematic review.
AB  - PURPOSE: In the foot and ankle literature, a wide range of patient-reported
      outcome measures (PROMs) is used, however, consensus as to which PROMs are
      preferred is lacking. Selection of a PROM is among other reasons, often based on
      measurement properties without considering the methodological quality of the
      studies that evaluate these measurement properties. The aim of current study was
      first to identify the most frequently used foot and ankle-specific PROMs in
      recent orthopaedic foot and ankle literature, and second to conduct a systematic
      review to synthesize and critically appraise the measurement properties of these
      PROMS. METHODS: Six PubMed indexed journals focussing on foot and ankle research
      were screened to identify most commonly used foot and ankle-specific PROMs over a
      2 year period (2015-2016). Subsequently, a systematic literature search was
      performed in PubMed, EMBASE, SPORTDiscus and Scopus to identify relevant studies
      on their measurement properties. Methodological quality assessment was performed
      using the COnsensus-based Standards for the selection of health Measurement
      INstruments (COSMIN) checklist, criteria for good measurement properties were
      applied, and a level of evidence was determined for the measurement properties of
      each domain of the questionnaires. RESULTS: The three most frequently reported
      PROMs were the Foot Function Index (FFI), the Foot and Ankle Outcome Score (FAOS)
      and the Foot and Ankle Activity Measure (FAAM). Among 2046 unique citations, 50
      studies were included evaluating these PROMs. Evidence to support the measurement
      properties of the FFI was mainly lacking due to poor methodological quality. More
      evidence was available for the measurement properties of the FAOS and the FAAM,
      but overall evidence supporting all measurement properties is not yet sufficient.
      CONCLUSION: The best available evidence retrieved in this review showed that the
      FAOS and the FAAM are promising outcome measures for evaluation of patients with
      foot and ankle conditions, but their shortcomings should be taken into account
      when interpreting results in clinical setting or trials. LEVEL OF EVIDENCE: I.

PMID- 29026936
TI  - A Comparative Study of Full-Thickness Blepharotomy Versus Transconjunctival
      Eyelid Lengthening in the Correction of Upper Eyelid Retraction in Graves'
      Orbitopathy.
AB  - BACKGROUND: The study was designed to compare the outcome of full-thickness
      blepharotomy and transconjunctival eyelid lengthening in the correction of upper
      eyelid retraction (UER) in patients with Graves' orbitopathy (GO). METHODS: This
      is a prospective randomized interventional study. Following ophthalmic
      examination, determination of the ocular surface disease index (OSDI) and
      photography, 27 patients with UER were randomly assigned to either graded full
      thickness blepharotomy (G1) or transconjunctival Muller muscle recession and
      graded disinsertion of the levator palpebrae superioris muscle (G2). Six months
      later, patients were reevaluated. Digital images were analyzed with the
      assistance of customized software. A standardized "normal range" of upper eyelid
      height and contour was calculated based on healthy controls. The outcome of the
      two groups was compared. RESULTS: Forty-seven eyelids of 27 patients (19 female)
      with UER were included. Twenty-seven eyelids (15 patients) were allocated to G1
      and 20 eyelids (12 patients) to G2. On average, surgery lasted 37.46 +/- 5.73 min
      in G1 and 32.70 +/- 8.39 min in G2. Based on the margin reflex distance, 93% of
      the eyelids in G1 and 85% in G2 were within the normal range after surgery. The
      corresponding figures for lid contour were 63 and 55%. Both groups displayed
      significant improvement in OSDI scores. No significant difference was observed in
      the overall comparison. CONCLUSIONS: The two surgical techniques were equally
      effective in the treatment of UER from GO. Postoperative contour outcomes were
      considerably worse in patients with severe UER than in patients with mild or
      moderate UER, regardless of group. LEVEL OF EVIDENCE II: This journal requires
      that authors assign a level of evidence to each article. For a full description
      of these Evidence-Based Medicine ratings, please refer to Table of Contents or
      the online Instructions to Authors www.springer.com/00266 . Study registered on
      ClinicalTrial.gov number: NCT01999790.

PMID- 29026935
TI  - Temporal-Spatial Evolution of Groundwater Nitrogen Pollution Over Seven Years in
      a Highly Urbanized City in the Southern China.
AB  - Understanding the temporospatial variation in nitrogen pollution in groundwater
      and the associated controlling factors is important to establish management
      practices that ensure sustainable use of groundwater. In this study, we analyzed
      inorganic nitrogen content (nitrate, nitrite, and ammonium) in 1164 groundwater
      samples from shallow, middle-deep, and deep aquifers in Zhanjiang, a highly
      urbanized city in the southern China. Our data span a range of 7 years from 2005
      to 2011. Results show that shallow aquifers had been heavily contaminated by
      nitrate and ammonium. Temporal patterns show that N contamination levels remained
      high and relatively stable over time in urban areas. This stability and high
      concentration is hypothesized as a result of uncontrolled, illicit sewer
      discharges from nearby business facilities. Groundwater in urban land and
      farmland displays systematic differences in geochemical characteristics.
      Collectively, our findings demonstrate the importance of continuously monitoring
      groundwater quality and strictly regulating sewage discharges in Zhanjiang.

PMID- 29026937
TI  - [Minimally invasive and robotic-assisted surgical management of upper
      gastrointestinal cancer].
AB  - Total minimally invasive upper gastrointestinal resections are currently mainly
      performed in centers. The advantages include reduction of operative trauma,
      magnified enlargement of the operation field and the resulting improvement in
      operative precision. Robotic-assisted minimally invasive esophagectomy (RAMIE)
      and laparoscopic/thoracoscopic minimally invasive esophagectomy (MIE) are
      currently the most commonly performed strategies for esophageal cancer.
      Laparoscopic (MIG) and robotic-assisted gastrectomy (RAG) are the equivalent
      procedures for gastric cancer. Due to the relatively low number of reported
      cases, no definitive statement regarding superiority of these procedures compared
      to standard open or hybrid procedures can be made; however, there is mounting
      evidence from high-volume centers in which these procedures are routinely
      performed that there might be an advantage regarding perioperative morbidity. All
      of the four procedures described are provided at our high-volume centers in a
      standardized manner and we are convinced of the benefits of these minimally
      invasive techniques with respect to morbidity compared to open and hybrid
      techniques. The additional costs of this technology have to be off-set against a
      possible reduction of morbidity, reduced cost for personnel and new operative
      options, such as real-time fluoroscopy.

PMID- 29026938
TI  - Global dietary calcium intake among adults: a systematic review.
AB  - Low calcium intake may adversely affect bone health in adults. Recognizing the
      presence of low calcium intake is necessary to develop national strategies to
      optimize intake. To highlight regions where calcium intake should be improved, we
      systematically searched for the most representative national dietary calcium
      intake data in adults from the general population in all countries. We searched
      13 electronic databases and requested data from domain experts. Studies were
      double-screened for eligibility. Data were extracted into a standard form. We
      developed an interactive global map, categorizing countries based on average
      calcium intake and summarized differences in intake based on sex, age, and
      socioeconomic status. Searches yielded 9780 abstracts. Across the 74 countries
      with data, average national dietary calcium intake ranges from 175 to 1233
      mg/day. Many countries in Asia have average dietary calcium intake less than 500
      mg/day. Countries in Africa and South America mostly have low calcium intake
      between about 400 and 700 mg/day. Only Northern European countries have national
      calcium intake greater than 1000 mg/day. Survey data for three quarters of
      available countries were not nationally representative. Average calcium intake is
      generally lower in women than men, but there are no clear patterns across
      countries regarding relative calcium intake by age, sex, or socioeconomic status.
      The global calcium map reveals that many countries have low average calcium
      intake. But recent, nationally representative data are mostly lacking. This
      review draws attention to regions where measures to increase calcium intake are
      likely to have skeletal benefits.

PMID- 29026939
TI  - [Minimally invasive osteosynthesis after ankle fractures in geriatric patients :
      Surgical technique with the aid of headless full thread screws].

PMID- 29026940
TI  - Advanced bioanalytics for precision medicine.
AB  - Precision medicine is a new paradigm that combines diagnostic, imaging, and
      analytical tools to produce accurate diagnoses and therapeutic interventions
      tailored to the individual patient. This approach stands in contrast to the
      traditional "one size fits all" concept, according to which researchers develop
      disease treatments and preventions for an "average" patient without considering
      individual differences. The "one size fits all" concept has led to many
      ineffective or inappropriate treatments, especially for pathologies such as
      Alzheimer's disease and cancer. Now, precision medicine is receiving massive
      funding in many countries, thanks to its social and economic potential in terms
      of improved disease prevention, diagnosis, and therapy. Bioanalytical chemistry
      is critical to precision medicine. This is because identifying an appropriate
      tailored therapy requires researchers to collect and analyze information on each
      patient's specific molecular biomarkers (e.g., proteins, nucleic acids, and
      metabolites). In other words, precision diagnostics is not possible without
      precise bioanalytical chemistry. This Trend article highlights some of the most
      recent advances, including massive analysis of multilayer omics, and new imaging
      technique applications suitable for implementing precision medicine. Graphical
      abstract Precision medicine combines bioanalytical chemistry, molecular
      diagnostics, and imaging tools for performing accurate diagnoses and selecting
      optimal therapies for each patient.

PMID- 29026941
TI  - Neutral alignment leads to higher knee society scores after total knee
      arthroplasty in preoperatively non-varus patients: a prospective clinical study
      using 3D-CT.
AB  - PURPOSE: The optimal coronal alignment is still under debate. However, in most of
      the studies, alignment was only assessed using radiographs, which are not
      accurate enough for assessment of tibial and femoral TKA position. The primary
      purpose of this study was to assess the relationship between coronal TKA
      alignment using 3D-reconstructed CTs and clinical outcome in patients with
      preoperative varus in comparison with patients with natural or valgus deformity.
      It was the hypothesis that neutral limb alignment shows a better outcome after
      TKA. METHODS: Prospectively collected data of 38 patients were included. The
      clinical and radiological follow-up was 24 months. The patients were grouped into
      two groups with regard to their preoperative limb alignment. Group A (varus)
      consisted of 21 patients with preoperative varus of 3 degrees  or more, while
      group B (non-varus) consisted of 17 patients with neutral (- 3 < 0 > + 3) or
      valgus alignment (> + 3). For assessment of TKA component position and
      orientation, 3D-reconstructed CT was used. The measurements of the deviation from
      the whole limb mechanical axis (HKA angle) and the joint line alignment in the
      femoral (mLDFA) and the tibial side (MPTA) were assessed in the preoperative leg
      as well as during follow-up after TKA. For clinical outcome assessment, the Knee
      Society Score (KSS) was used at 1 and 2 years postoperatively. Correlation
      between KSS score and each variable was done using a linear and quadratic
      regression model (p < 0.05). RESULTS: The mean postoperative HKA angle was - 1.3
      (varus) in the varus group and + 1.4 (valgus) in the non-varus group. Overall,
      significant correlations between the preoperative and postoperative alignments
      were found. In the preoperatively non-varus group, a highly significant
      correlation was found between neutral limb alignment (HKA = 0 degrees  +/- 3
      degrees ) and higher KSS (r 2 = 0.74, p = 0.00). In the varus group, no
      correlation was found between the postoperative whole limb alignment and the
      components' position in the coronal plane to KSS score. CONCLUSION: A significant
      correlation was found between neutral limb alignment and higher KSS only in
      patients with preoperative non-varus alignment. The concept of constitutional
      varus alignment is still under debate. Moreover, it appears that one should aim
      for a more individualized, alignment target based on the individual knee
      morphotype. LEVEL OF EVIDENCE: Diagnostic study, Level II.

PMID- 29026942
TI  - The effects of subclinical neck pain on sensorimotor integration following a
      complex motor pursuit task.
AB  - Recurrent subclinical neck pain (SCNP) may be associated with neural plastic
      changes in sensory processing and sensorimotor integration (SMI); however, its
      impact on motor learning has not been investigated. The aim of this study was to
      investigate whether SCNP alters neural markers of SMI during a complex motor
      acquisition task as compared to a healthy control group. Peripheral N9, spinal
      N13, brainstem N18, and cortical N20, P25, N24 and N30 early somatosensory evoked
      potentials (SEPs) were recorded following median nerve stimulation for 24
      participants (12 control and 12 SCNP) before and after a 10-min tracing motor
      task intervention. Retention was assessed 24-48 h later. Significant amplitude
      differences were observed for both N18 and N24 SEP waveforms between groups,
      indicating there may be a difference in SMI due to altered afferent input as a
      result of SCNP. Accuracy increased significantly for both groups post-motor
      training; however, at retention only the control group showed an additional
      increase in accuracy. Both N18 and N24 SEP peaks are linked with cerebellar
      pathways, suggesting that SCNP impacts these connections. Significant
      correlations between these peaks and performance data were also seen. The
      differential changes in neurophysiological markers of SMI seen in SCNP suggest
      that SEPs have the potential to be used as an early screening tool for those at
      risk of having maladaptive neural plastic changes in response to motor training
      as a result of SCNP.

PMID- 29026943
TI  - Quorum sensing inhibitors: can endophytes be prospective sources?
AB  - Endophytes are microbes which reside inside the plant tissues asymptomatically or
      causing pathogenicity to the host plant for a brief period. Owing to their
      presence in a specialized niche, endophytes are capable of synthesizing diverse
      types of bioactive molecules. Continuous development of resistance mechanism by
      pathogens to the currently available health treatments and pharmaceuticals has
      led researchers to explore new therapeutic agents. Quorum sensing has a role in
      the development of microbial pathogenic traits including biofilm formation.
      Utilization of quorum sensing (QS) inhibitors in antivirulence approach against
      pathogenesis is one of the innovative strategies. Endophytic microbes provide a
      plethora of such required bioactive molecules. This review summarizes the
      bioprospecting of endophytic microbes for production of novel QS inhibitors. At
      the outset, an overview is presented about the QS and QS inhibition followed by a
      summary on the endophytes as a treasure trove of bioactive metabolites,
      particularly the QS inhibitors. Next, we have outlined screening, purification,
      production, and application of QS inhibitors starting from the isolation of
      endophytic microbes. There is huge prospect for endophytes in the domain of human
      healthcare and food industry, provided that we develop a comprehensive
      understanding of the biology of endophyte and its ecosystem.

PMID- 29026944
TI  - Improving elution strategies for Chelex(r)-DGT passive samplers.
AB  - Elution of Chelex(r) binding layers, commonly used for the diffusive gradients in
      thin films technique (DGT), is recognized as the most important contributor to
      the uncertainty of DGT measurements. Limiting uncertainty requires the use of
      optimized procedures and suitable elution recoveries (f e ). This work therefore
      investigated elution robustness to propose improved strategies. A wide range of
      conditions were investigated for the main elution parameters (Chelex(r) particle
      size, elution time, Chelex(r) loading, and eluent concentration and volume) on
      Al(III), Cd(II), Co(II), Cr(III), Cu(II), Ni(II), Pb(II), and Zn(II). Results
      showed that the choice of elution conditions should be a compromise driven by
      study constrains in terms of accuracy, repeatability, sensitivity, and targeted
      elements. Using experimentally determined recoveries should improve accuracy by
      approximately 5 to 10% compared to the use of recoveries from the literature.
      Fast elution of 1 h can be achieved without significant loss of recovery and
      repeatability except for Cr(III) (8 h minimum). Elution recovery depended on
      Chelex(r) loading for Zn and Cr and introducing recoveries adapted to the loading
      could improve accuracy up to, respectively, 11 and 27%. When standard recoveries
      are used, a 0.85 f e value would be more appropriate than the common value of 0.8
      to minimize inaccuracy (except for Cr). Some flexibility can be applied to
      elution conditions without a significant change in recovery for most elements:
      HNO3 concentration of 1-15 M, volume of 1-2 mL, duration of 8-48 h. Cr(III) was
      unique in its sensitivity to elution condition variations; thus, choice is more
      restricted for this element. Graphical abstract Decisional tree for choosing
      elution procedure and recoveries for Chelex(r)-DGT.

PMID- 29026945
TI  - TSPO PET using 18F-GE-180: a new perspective in neurooncology?

PMID- 29026946
TI  - PSMA targeted radioligandtherapy in metastatic castration resistant prostate
      cancer after chemotherapy, abiraterone and/or enzalutamide. A retrospective
      analysis of overall survival.
AB  - AIM: Our aim was to evaluate overall survival and parameters prognosticating
      longer survival in a large and homogeneous group of patients treated with 177Lu
      PSMA-617 radioligand therapy with heavily pretreated advanced metastatic
      castration resistant prostate cancer. METHODS: A total of 104 patients were
      treated with 351 cycles of 177Lu-PSMA-617. Prostate specific antigen (PSA)
      changes after the first cycle of therapy were documented prior to a second cycle.
      Patients were followed-up for overall survival (OS). Any PSA decline, PSA decline
      >=50%, initial PSA, alkaline phosphatase (ALP), lactate dehydrogenase (LDH),
      visceral metastases and cumulative injected activity were analyzed and evaluated
      according to OS. Multivariable analysis with parameters with a p-value <=0.05 in
      univariate analysis was performed, additionally adjusting for age and presence of
      visceral metastases. RESULTS: A total of 51 patients (49%) died during the
      observation period. The majority of patients (97%) presented with bone
      metastases, 77% with lymph node metastases and 32% with visceral metastases. All
      patients were treated with at least one line of chemotherapy. Either abiraterone
      or enzalutamide had been given in 100% of the patients. Any PSA decline occurred
      in 70 (67%) and a PSA decline >=50% in 34 (33%) of patients after the first
      cycle. The median OS was 56.0 weeks (95%CI: 50.5-61.5). Initial PSA decline
      >=50%, initial LDH, visceral metastases, second line chemotherapy or prior radium
      223 did not have an effect on survival, whereas any initial PSA decline, initial
      ALP <220 U/L and cumulative injected activity >=18.8 GBq were associated with a
      longer survival. A step-by-step analysis revealed a PSA decline >=20.87% as the
      most noticeable cut-off prognosticating longer survival, which remained an
      independent prognosticator of improved OS in the multivariate analysis.
      CONCLUSION: 177Lu-PSMA-617 RLT is a new effective therapeutic and seems to
      prolong survival in patients with advanced mCRPC pretreated with chemotherapy,
      abiraterone and/or enzalutamide.

PMID- 29026947
TI  - PET-guided clinical trials in Hodgkin lymphoma: to agree or not to agree, that is
      the reviewer's question.

PMID- 29026948
TI  - Comparison of Dexamethasone-Dimenhydrinate and Dexamethasone-Ondansetron in
      Prevention of Nausea and Vomiting in Postoperative Patients.

PMID- 29026949
TI  - A filamentous bacteriophage targeted to carcinoembryonic antigen induces tumor
      regression in mouse models of colorectal cancer.
AB  - Colorectal cancer is a deadly disease, which is frequently diagnosed at advanced
      stages, where conventional treatments are no longer effective. Cancer
      immunotherapy has emerged as a new form to treat different malignancies by
      turning-on the immune system against tumors. However, tumors are able to evade
      antitumor immune responses by promoting an immunosuppressive microenvironment.
      Single-stranded DNA containing M13 bacteriophages are highly immunogenic and can
      be specifically targeted to the surface of tumor cells to trigger inflammation
      and infiltration of activated innate immune cells, overcoming tumor-associated
      immunosuppression and promoting antitumor immunity. Carcinoembryonic antigen
      (CEA) is highly expressed in colorectal cancers and has been shown to promote
      several malignant features of colorectal cancer cells. In this work, we targeted
      M13 bacteriophage to CEA, a tumor-associated antigen over-expressed in a high
      proportion of colorectal cancers but largely absent in normal cells. The CEA
      targeted M13 bacteriophage was shown to specifically bind to purified CEA and CEA
      expressing tumor cells in vitro. Both intratumoral and systemic administration of
      CEA-specific bacteriophages significantly reduced tumor growth of mouse models of
      colorectal cancer, as compared to PBS and control bacteriophage administration.
      CEA-specific bacteriophages promoted tumor infiltration of neutrophils and
      macrophages, as well as maturation dendritic cells in tumor-draining lymph nodes,
      suggesting that antitumor T-cell responses were elicited. Finally, we
      demonstrated that tumor protection provided by CEA-specific bacteriophage
      particles is mediated by CD8+ T cells, as depletion of circulating CD8+ T cells
      completely abrogated antitumor protection. In summary, we demonstrated that CEA
      specific M13 bacteriophages represent a potential immunotherapy against
      colorectal cancer.

PMID- 29026952
TI  - Spatially and angularly resolved spectroscopy for in-situ estimation of
      concentration and particle size in colloidal suspensions.
AB  - Successful implementation of process analytical technology (PAT) hinges on the
      ability to make continuous or frequent measurements in-line or at-line of
      critical product attributes such as composition and particle size, the latter
      being an important parameter for particulate processes such as suspensions and
      emulsions. A novel probe-based spatially and angularly-resolved diffuse
      reflectance measurement (SAR-DRM) system is proposed. This instrument, along with
      appropriate calibration models, is designed for online monitoring of
      concentration of chemical species and particle size of the particulate species in
      process systems involving colloidal suspensions. This measurement system was
      investigated using polystyrene suspensions of various particle radius and
      concentration to evaluate its performance in terms of the information obtained
      from the novel configuration which allows the measurement of a combination of
      incident light at different angles and collection fibres at different distances
      from the source fibres. Different strategies of processing and combining the SAR
      DRM measurements were considered in terms of the impact on partial least squares
      (PLS) model performance. The results were compared with those obtained using a
      bench-top instrument which was used as the reference (off-line) instrument for
      comparison purposes. The SAR-DRM system showed similar performance to the bench
      top reference instrument for estimation of particle radius, and outperforms the
      reference instrument in estimating particle concentration. The investigation
      shows that the improvement in PLS regression model performance using the SAR-DRM
      system is related to the extra information captured by the SAR-DRM configuration.
      The differences in SAR-DRM spectra collected by the different collection fibres
      from different angular source fibres are the dominant reason for the significant
      improvement in the model performance. The promising results from this study
      suggest the potential of the SAR-DRM system as an online monitoring tool for
      processes involving suspensions. Graphical abstract A probe designed to acquire
      diffuse reflectance measurements at different source-detector distances for three
      incidence angles 0 degrees , 30 degrees  and 45 degrees  was used to estimate
      particle size and concentration of polystyrene beads in aqueous suspension using
      partial least squares calibration models.

PMID- 29026950
TI  - The prognostic value of 18F-FDG PET/CT prior to liver transplantation for
      nonresectable colorectal liver metastases.
AB  - PURPOSE: The main objective of this study was to evaluate the prognostic value of
      volumetric and metabolic information derivied from F-18 fluorodeoxyglucose
      positron emission tomography (18F-FDG PET) in combination with computed
      tomography (CT) prior to liver transplantation (LT) in patients with
      nonresectable colorectal liver metastases (CLM). Due to scarcity of liver grafts,
      prognostic information enabling selection of candidates who will gain the highest
      survival after LT is of vital importance. 18F-FDG PET/CT was a part of the
      preoperative study protocol. Patients without evidence of extrahepatic malignant
      disease on 18F-FDG PET/CT who also fulfilled all the other inclusion criteria
      underwent LT. METHODS: The preoperative 18F-FDG PET/CT examinations of all
      patients included in the SECA (secondary cancer) study were retrospectively
      assessed. Maximum, mean and peak standardized uptake values (SUVmax, SUVmean and
      SUVpeak), tumor to background (T/B) ratio, metabolic tumor volume (MTV) and total
      lesion glycolysis (TLG) were measured and calculated for all liver metastases.
      Total MTV and TLG were calculated for each patient. Cut-off values were
      determined for each of these parameters by using receiver operating
      characteristic (ROC) analysis dividing the patients into two groups. One, three
      and five-year overall survival (OS) and disease free survival (DFS) for patients
      over and under the cut-off value were compared by using the Kaplan-Meier method
      and log rank test. RESULTS: Twenty-three patients underwent LT in the SECA study.
      Total MTV and TLG under the cut-off values were significantly correlated to
      improved OS at three and five years (p = 0.027 and 0.026) and DFS (p = 0.01).
      One, three and five-year OS and DFS were not significantly related to SUVmax,
      SUVmean, SUVpeak or T/B-ratio. CONCLUSION: Total MTV and TLG from 18F FDG PET/CT
      prior to LT for nonresectable CLM were significantly correlated to improved three
      and five-year OS and DFS and can potentially improve the patient selection for
      LT.

PMID- 29026951
TI  - Multimodal correlation of dynamic [18F]-AV-1451 perfusion PET and neuronal
      hypometabolism in [18F]-FDG PET.
AB  - PURPOSE: Cerebral glucose metabolism measured with [18F]-FDG PET is a well
      established marker of neuronal dysfunction in neurodegeneration. The tau-protein
      tracer [18F]-AV-1451 PET is currently under evaluation and shows promising
      results. Here, we assess the feasibility of early perfusion imaging with AV-1451
      as a substite for FDG PET in assessing neuronal injury. METHODS: Twenty patients
      with suspected neurodegeneration underwent FDG and early phase AV-1451 PET
      imaging. Ten one-minute timeframes were acquired after application of 200 MBq AV
      1451. FDG images were acquired on a different date according to clinical
      protocol. Early AV-1451 timeframes were coregistered to individual FDG-scans and
      spatially normalized. Voxel-wise intermodal correlations were calculated on
      within-subject level for every possible time window. The window with highest
      pooled correlation was considered optimal. Z-transformed deviation maps (ZMs)
      were created from both FDG and early AV-1451 images, comparing against FDG images
      of healthy controls. RESULTS: Regional patterns and extent of perfusion deficits
      were highly comparable to metabolic deficits. Best results were observed in a
      time window from 60 to 360 s (r = 0.86). Correlation strength ranged from r =
      0.96 (subcortical gray matter) to 0.83 (frontal lobe) in regional analysis. ZMs
      of early AV-1451 and FDG images were highly similar. CONCLUSION: Perfusion
      imaging with AV-1451 is a valid biomarker for assessment of neuronal dysfunction
      in neurodegenerative diseases. Radiation exposure and complexity of the
      diagnostic workup could be reduced significantly by routine acquisition of early
      AV-1451 images, sparing additional FDG PET.

PMID- 29026953
TI  - Application of molecularly imprinted polymers for the analysis of polycyclic
      aromatic hydrocarbons in lipid matrix-based biological samples.
AB  - High-accuracy analyses of polycyclic aromatic hydrocarbons (PAHs) in lipid matrix
      based biological samples are highly necessary. We investigated the cleanup
      performance of the commercially available molecularly imprinted polymers (MIPs)
      to analyze PAHs in various biological samples (i.e., butter, peanut oil, pork
      belly, and human umbilical cord), and compared this method with the commonly used
      gel permeation chromatography (GPC). After primary cleanup with a MIP or GPC
      column, the extracts were further cleaned with a neutral aluminum oxide column.
      Then, we measured 16 PAH congeners using gas chromatography-mass spectrometry.
      The MIP method allowed PAH recovery levels as high as those measured with the GPC
      method to be obtained. More than 95% of the crude fats of butter, peanut oil, and
      pork belly were removed, although only ~ 50% were removed for human umbilical
      cord. The scan-mode ion chromatograms of the final extracts cleaned with the MIP
      method had responses similar to solvent blank for the four types of samples,
      which were slightly better than those cleaned with GPC. Moreover, the PAH
      concentrations in the MIP operation blank were generally lower than those of GPC
      operation blanks. These results indicated that MIP could be applied to the
      analysis of PAHs in various lipid matrix-based biological samples. Graphical
      abstract The schematic diagram of a molecularly imprinted polymer column and the
      elution curves of polycyclic aromatic hydrocarbons and crude fats of various
      biological samples.

PMID- 29026954
TI  - Selective extraction and determination of chlorogenic acids as combined quality
      markers in herbal medicines using molecularly imprinted polymers based on a mimic
      template.
AB  - We describe a solid-phase extraction adsorbent based on molecularly imprinted
      polymers (MIPs), prepared with use of a mimic template. The MIPs were used for
      the selective extraction and determination of three chlorogenic acids as combined
      quality markers for Lonicera japonica and Lianhua qingwen granules. The
      morphologies and surface groups of the MIPs were assessed by scanning electron
      microscopy, Brunauer-Emmett-Teller surface area analysis, and Fourier transform
      infrared spectroscopy. The adsorption isotherms, kinetics, and selectivity of the
      MIPs were systematically compared with those of non-molecularly imprinted
      polymers. The MIPs showed high selectivity toward three structurally similar
      chlorogenic acids (chlorogenic acid, cryptochlorogenic acid, and neochlorogenic
      acid). A procedure using molecularly imprinted solid-phase extraction coupled
      with high-performance liquid chromatography was established for the determination
      of three chlorogenic acids from Lonicera japonica and Lianhua qingwen granules.
      The recoveries of the chlorogenic acids ranged from 93.1% to 101.4%. The limits
      of detection and limits of quantification for the three chlorogenic acids were
      0.003 mg g-1 and 0.01 mg g-1, respectively. The newly developed method is thus a
      promising technique for the enrichment and determination of chlorogenic acids
      from herbal medicines. Graphical Abstract Mimic molecularly imprinted polymers
      for the selective extraction of chlorogenic acids.

PMID- 29026955
TI  - Indolent Rib Osteomyelitis Following Breast Implant Reconstruction: An Unusual
      Case and Review of the Literature.
AB  - : Rib osteomyelitis is an infrequently occurring but important complication of
      breast implant surgery. Although prosthetic or surgical site infection (SSI) and
      rib osteomyelitis as separate entities are well described in the literature, only
      five cases of rib or sternal osteomyelitis related to implant placement have been
      reported globally. Historically patients who experience this complication have
      not demonstrated an identifiable prevalence of the traditional risk factors
      associated with SSI or rib osteomyelitis. This report describes the sequence of
      clinical manifestations of an unusual case of breast implants complicated by rib
      osteomyelitis. A 56-year-old female underwent mastectomy and insertion of tissue
      expanders for bilateral invasive ductal carcinoma following which the tissue
      expanders became infected in the early postoperative period and were subsequently
      removed. The patient underwent successful expander insertion and subsequent
      implant exchange surgery several years later and enjoyed an uncomplicated
      recovery from this. Following nipple reconstruction more than 12 months after
      successful implant placement, she presented with Staphylococcus epidermidis
      bacteremia and a left-sided clinical peri-implant infection. Upon removal of her
      implant, an intraoperative discovery of rib necrosis/osteomyelitis was made for
      which she was treated. To provide context, the literature was reviewed for other
      reported cases of rib osteomyelitis following breast implant surgery. This
      patient, in combination with others reported in the literature, emphasises the
      diagnostic difficulties posed by this condition as a result of its low incidence
      and variable or absent clinical features. LEVEL OF EVIDENCE V: This journal
      requires that authors assign a level of evidence to each article. For a full
      description of these Evidence-Based Medicine ratings, please refer to the Table
      of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 29026956
TI  - Peptide self-assembly assisted signal labeling for an electrochemical assay of
      protease activity.
AB  - Peptide self-assembly holds tremendous promise for a range of applications in
      chemistry and biology. In the work reported here, we explored the potential
      functions of peptide self-assembly in electrochemical bioanalysis by developing a
      peptide self-assembly assisted signal labeling strategy for assaying protease
      activity. The fundamental principle of this assay is that target-protease
      catalyzed specific proteolytic cleavage blocks self-assembly between the probe
      peptide and signal peptide, thus preventing the signal labeling of electroactive
      silver nanoparticles on the electrode surface, which in turn causes the
      electrochemical signal to decrease. Using trypsin as an example protease target,
      the linear range of this assay was found to be 1 ng mL-1 to 100 mg mL-1, and its
      detection limit was 0.032 ng mL-1, which are better than the corresponding
      parameters for previously reported assays. Further experiments also highlighted
      the good selectivity of the assay method and demonstrated its usability when
      applied to serum samples. Therefore, this report not only introduces a valuable
      tool for assaying protease activity, but it also promotes the utilization of
      peptide self-assembly in electrochemical bioanalysis, as this approach has great
      potential for practical use in the future.

PMID- 29026957
TI  - Autologous Buccal Micro-Mucosa Free Graft combined with Posterior Scrotal Flap
      Transfer for Vaginoplasty in Male-To-Female Transsexuals: A Pilot Study.
AB  - BACKGROUND: The inverted peno-scrotal flap method is considered the standard
      method of vaginoplasty in male-to-female genital reassignment surgery. Though
      with numerous advantages, the method has its limitations regarding skin texture,
      lack of inherent lubrication, and that the tissues for creating the labia depend
      on the amount of tissues remaining after vaginoplasty. Our purpose was to
      describe the procedure and outcome of vaginoplasty applying a new technique:
      autologous buccal micro-mucosa free graft combined with posterior scrotal flap
      transfer, which could solve some of the problems the previous methods had.
      METHODS: Nine male-to-female transsexual patients received our new method of
      vaginoplasty from July 2010-October 2015. We described the details of the
      surgical procedure and evaluated the long-term anatomical and functional
      outcomes. RESULTS: In a mean clinical follow-up period of 25.3 months and phone
      interview follow-up of 50.3 months, we observed that the neovaginas in the nine
      cases were all of sufficient volume, lined with mucosa, with natural mucosal
      discharge. The oral donor sites resulted in no visible scars or malfunction.
      Eight patients experienced uneventful postoperative periods, while one patient
      suffered from scrotal flap prolapse. All the patients were sexually active and
      reported sexual satisfaction, with no need of lubrication. CONCLUSION: The
      reported technique achieves the outcomes of creating a neovagina of sufficient
      volume, without serious stenosis in long-term follow-up. The neovagina is lined
      with mucosa and has appropriate lubrication as well as good sexual sensation. The
      reported method is easy and economical to perform and retains enough tissues for
      vulvoplasty to achieve a superior cosmetic appearance, with rare risk of
      complications and donor area malfunction. Additionally, this technique is
      feasible and advantageous to the patients who have insufficient peno-scrotal skin
      for neovaginal lining as well as those with unfavorable previous vaginoplasty.
      All of these indicate that this technique is a promising option for vaginoplasty
      in male-to-female transsexual surgery. LEVEL OF EVIDENCE IV: This journal
      requires that authors assign a level of evidence to each article. For a full
      description of these Evidence-Based Medicine ratings, please refer to the Table
      of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 29026958
TI  - Histological changes caused by the prolonged placement of ureteral access
      sheaths: an experimental study in porcine model.
AB  - The objective is to evaluate the histological damage to the ureteral wall caused
      by the prolonged placement of an access sheath in porcine model. Six ureters from
      three female pigs were randomized into three groups. In each group, an UAS with
      different indwelling time was inserted. 9.5/11.5 Fr Flexor(r) ureteral access
      sheaths were inserted in both ureters with left indwelling for 30 min and right
      for 60 min. The ureteral access sheath was advanced up to the proximal ureter. No
      resistance was observed during the insertion. Ureters were harvested in
      immediately after the sheath placement process in one pig. The ureters of the
      remaining two pigs were removed at 1 and 2 weeks after the procedure,
      respectively. Histological examination took place also in these specimens.
      Ureters with an indwelling time of 30 min: histological examination of the ureter
      after immediate dissection revealed signs of acute inflammation at the distal
      ureter. The ureter dissected at 1 week showed minimal focal transmural
      inflammation along its length with minimal epithelial hyperplasia. The ureter
      dissected at 2 weeks, no signs of inflammation. Ureters with an indwelling time
      of 60 min: histological examination of the immediately dissected ureter revealed
      signs of acute inflammation at the distal ureter. At 1 week, chronic transmural
      inflammation was predominantly observed in the distal ureter. At 2 weeks, minimal
      transmural inflammation was observed. The use of UAS did not cause any severe
      histological damage on porcine ureters. Acute signs of inflammation gradually
      recovered within 2 weeks.

PMID- 29026959
TI  - Effects of Timing of Appendectomy on the Risks of Perforation and Postoperative
      Complications of Acute Appendicitis.
AB  - BACKGROUND: It is generally believed that appendectomy should be performed
      immediately to prevent perforation and complications. Therefore, our objectives
      were to investigate the effect of timing of appendectomy on the incidence of
      perforation and complications. METHODS: We retrospectively reviewed the medical
      records of patients who underwent laparoscopic appendectomy between January 2014
      and June 2015. The time from symptom onset to appendectomy was categorized into
      three periods: time from symptom onset to hospital admission (symptomatic time),
      time from admission to appendectomy (hospitalization time), and time from symptom
      onset to appendectomy [symptomatic period + hospitalization period (overall
      time)]. Multivariable analyses were performed to identify independent factors
      associated with perforation and complications. RESULTS: A total of 1753 patients
      were included in the present study. Perforation occurred in 28.2% of patients,
      and postoperative complications occurred in 10.0% of patients. Multivariable
      analysis showed that BT > 38  degrees C (P = 0.006), WBC count >13,000 cells/ul
      (P = 0.02), neutrophil ratio >80% (P < 0.001), and symptomatic time >24 h (P <
      0.001) were independent factors of appendiceal perforation, while the neutrophil
      ratio >80% (P < 0.001) and symptomatic time >48 h (P = 0.003) were independently
      associated with complications. CONCLUSIONS: The present study showed that the
      symptomatic time and overall time were significantly associated with perforation
      and complications, whereas hospitalization time was not associated with either
      perforation or complications.

PMID- 29026960
TI  - Management of Tuberous Breast Deformities: Review of Long-Term Outcomes and
      Patient Satisfaction.

PMID- 29026961
TI  - Outcome of In Situ Septoplasty and Extracorporeal Subtotal Septal Reconstruction
      in Crooked Noses: A Randomized Self-Controlled Study.
AB  - IMPORTANCE: Severe dorsal deviations in crooked noses are treated by either in
      situ septoplasty with asymmetric spreader grafts (ISS) or extracorporeal subtotal
      septal reconstruction (ECS). To our knowledge, except one retrospective study,
      there is no other that compares the objective and subjective results of these two
      treatment modalities. OBJECTIVE: The aim of this study was to compare the
      aesthetic and functional outcomes of ECS and ISS in crooked noses. DESIGN,
      SETTING AND PARTICIPANTS: This study was carried out on 40 patients (ISS in 20
      patients and ECS in 20 patients) who underwent external rhinoplasty surgery due
      to crooked noses between May 2014 and January 2016. While performing rhinoplasty
      on the patients, the decision of whether to use the ECS or ISS technique was
      randomized in a sequential fashion. MAIN OUTCOMES AND MEASURES: Surgical outcomes
      were assessed and compared using the anthropometric measurement of photographs
      with Rhinobase software. Subjective assessments of nasal obstruction and
      aesthetic satisfaction were evaluated with a visual analog scale. RESULTS: There
      was a significant difference between rhinion deviation angle, supratip deviation
      angle (SDA) and tip deviation angle pre- and postoperatively in the ECS group,
      whereas in the ISS group, except SDA, all other postoperative angles were
      significantly improved from preoperative values (p = 0.218). The nasal tip
      projection in the ECS and ISS groups was 29.48, 31.5 preoperatively and 29.78,
      31.26 postoperatively. The mean postoperative nasal tip projection value (p >
      0.005) did not change significantly compared to the preoperative value in both
      groups. The mean postoperative value of nasolabial (p = 0.226) angle did not
      change significantly compared to the mean preoperative one in the ECS group.
      However, in the ISS group, the mean postoperative value of nasolabial (p = 0.001)
      angle significantly improved compared to the mean preoperative value. There was
      significant improvement in both groups, while improvements in both functional and
      aesthetic outcomes were much higher in the extracorporeal group. None of the
      patients had postoperative nasal obstruction that required revision surgery. One
      patient underwent revision rhinoplasty due to an irregularity on the nasal dorsum
      in the ECS group. CONCLUSIONS AND RELEVANCE: This is the first study that
      compares subjective and objective aesthetic and functional outcomes of crooked
      nose surgery according to two common septoplasty techniques in a randomized self
      controlled fashion. This study was effective in both objectively and subjectively
      comparing the functional and aesthetic aspect of the patients submitted to two
      common different techniques of treatment of nasal deviations in crooked nose
      patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level
      of evidence to each article. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 29026962
TI  - Abdominal Contouring Outcomes in Class III Obesity: Analysis of the ACS-NSQIP
      Database.
AB  - BACKGROUND: Obesity may increase the risk of complications following abdominal
      contouring. The aim of this study is to evaluate panniculectomy outcomes in
      patients with class III obesity (BMI > 40 kg/m2). METHODS: The American College
      of Surgeon's National Surgical Quality Improvement Program ACS-NSQIP (2010-2014)
      was used to identify patients who underwent panniculectomy. Class III obesity
      patients were identified. Demographics, comorbidities and postoperative outcomes
      were evaluated. Risk-adjusted multivariate logistic regression analyses were
      performed to assess impact of class III obesity on panniculectomy outcomes.
      RESULTS: A total of 4497 panniculectomies were identified. Of these, 545 (12.1%)
      were performed in patients with class III obesity. This group was older (mean age
      50.3 vs. 45.9, p < 0.01) with a higher proportion of men (23.4 vs. 12.4%, p <
      0.01). Class III obesity group also had higher rates of comorbidities (p < 0.01).
      Postoperatively, class III obesity patients experienced much higher rates of
      wound complications (17.8 vs. 6.8%), sepsis (3.3 vs. 0.8%), venous
      thromboembolism (1.5 vs. 0.7%) and medical complications (6.4 vs. 1.8%), p <
      0.05. Additionally, this group had higher rates of unplanned reoperation (9.2 vs.
      3.7%) and 30-day readmissions (3.5 vs. 1.0%), p < 0.01. On risk-adjusted
      multivariate regression analyses, class III obesity was independently associated
      with increased risk of wound complications (OR 2.22, p < 0.01), sepsis (OR 3.53,
      p < 0.01), medical adverse events (OR 1.98, p < 0.05), unplanned reoperation (OR
      1.62, p < 0.05) and 30-day readmission (OR 2.30, p < 0.05). CONCLUSION: Class III
      obesity patients are at significantly increased risk of adverse outcomes
      following abdominal contouring. Plastic surgeons should consider these risks for
      counseling and preoperative risk optimization. LEVEL OF EVIDENCE IV: This journal
      requires that authors assign a level of evidence to each article. For a full
      description of these Evidence-Based Medicine ratings, please refer to the Table
      of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 29026964
TI  - Effects of Nitrogen and Phosphorus Fertilizer and Topsoil Amendment on Native
      Plant Cover in Roadside Revegetation Projects.
AB  - Establishing vegetation on roadsides following construction can be challenging,
      especially for relatively slow growing native species. Topsoil is generally
      removed during construction, and the surface soil following construction ("cut
      slope soils") is often compacted and low in nutrients, providing poor growing
      conditions for vegetation. Nebraska Department of Transportation (NDOT) protocols
      have historically called for nitrogen (N) and phosphorus (P) fertilization when
      planting roadside vegetation following construction, but these recommendations
      were developed for cool-season grass plantings and most current plantings use
      slower-establishing, native warm-season grasses that may benefit less than
      expected from current planting protocols. We evaluated the effects of nitrogen
      and phosphorus fertilization, and also topsoil amendment, on the foliar cover of
      seeded and non-seeded species planted into two post-construction roadside sites
      in eastern Nebraska. We also examined soil movement to determine how planting
      protocols and plant growth may affect erosion potential. Three years after
      planting, we found no consistent effects of N or P fertilization on foliar cover.
      Plots receiving topsoil amendment had 14% greater cover of warm-season grasses,
      10% greater total foliar cover, and 4-13% lower bare ground (depending on site)
      than plots without topsoil. None of the treatments consistently affected soil
      movement. We recommend that NDOT change their protocols to remove N and P
      fertilization and focus on stockpiling and spreading topsoil following
      construction.

PMID- 29026963
TI  - An Evaluation of the Role of Simulation Training for Teaching Surgical Skills in
      Sub-Saharan Africa.
AB  - BACKGROUND: An estimated 5 billion people worldwide lack access to any surgical
      care, whilst surgical conditions account for 11-30% of the global burden of
      disease. Maximizing the effectiveness of surgical training is imperative to
      improve access to safe and essential surgical care on a global scale. Innovative
      methods of surgical training have been used in sub-Saharan Africa to attempt to
      improve the efficiency of training healthcare workers in surgery. Simulation
      training may have an important role in up-scaling and improving the efficiency of
      surgical training and has been widely used in SSA. Though not intended to be a
      systematic review, the role of simulation for teaching surgical skills in Sub
      Saharan Africa was reviewed to assess the evidence for use and outcomes. METHODS:
      A systematic search strategy was used to retrieve relevant studies from
      electronic databases PubMed, Ovid, Medline for pertinent articles published until
      August 2016. Studies that reported the use of simulation-based training for
      surgery in Africa were included. RESULTS: In all, 19 articles were included. A
      variety of innovative surgical training methods using simulation techniques were
      identified. Few studies reported any outcome data. Compared to the volume of
      surgical training initiatives that are known to take place in SSA, there is very
      limited good quality published evidence for the use of simulation training in
      this context. CONCLUSIONS: Simulation training presents an excellent modality to
      enhance and improve both volume and access to high quality surgical skills
      training, alongside other learning domains. There is a desperate need to
      meticulously evaluate the appropriateness and effectiveness of simulation
      training in SSA, where simulation training could have a large potential
      beneficial impact. Training programs should attempt to assess and report learner
      outcomes.

PMID- 29026965
TI  - Cutting the Holy Dome: The Evolution of Vertical Alar Resection.
AB  - INTRODUCTION: Dome division or vertical dome division (VDD) is a tip plasty
      technique that is effective when applied appropriately to suitable patients. For
      15 years, we have used VDD and made modifications as needed. In classical VDD,
      the dome area is cut and left to heal, but experience shows that additional
      components are needed to complement dome division, such as sutures or grafts. In
      this study, we retrospectively analysed our rhinoplasty patients in whom we used
      vertical alar resection (VAR) to assess the advantages and disadvantages of this
      technique. To our knowledge, this is one of the most exhaustive studies of VDD,
      including over 3000 patients. MATERIALS AND METHODS: This retrospective case
      series reviewed the charts of 3965 patients who underwent VAR between 2000 and
      2015. All patients were operated on by the senior surgeon. Dome division was used
      for various reasons, including a deformed tip area in revision rhinoplasties,
      droopy nose, wide tip, pinched nose, tip asymmetry, and overprojected nasal tip.
      Patients were excluded if they had septal deviation that enabled tip rotation, or
      a dorsum problem that caused tip asymmetry. RESULTS: The study included 3965
      patients (3172 women and 793 men) who underwent open rhinoplasty from 2000 to
      2015. The mean patient age was 28.3 years (range 18-50 years). The mean clinical
      follow-up duration was 11.2 years. CONCLUSION: In conclusion, this technique is
      capable of modifying all parameters of the nasal tip (projection, rotation, and
      volume), as required, at the same time, addressing many tip problems. LEVEL OF
      EVIDENCE IV: This journal requires that authors assign a level of evidence to
      each article. For a full description of these Evidence-Based Medicine ratings,
      please refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 29026966
TI  - The Clinical Implications of Liver Resection Margin Size in Patients with
      Hepatocellular Carcinoma in Terms of Positron Emission Tomography Positivity.
AB  - BACKGROUND: The positivity of positron emission tomography (PET) in
      hepatocellular carcinoma (HCC) correlates with aggressive tumor factors and poor
      survival. Adequate resection margin size is still a topic of debate. We analyzed
      the clinical implications of resection margin size in patients with HCC in terms
      of PET positivity. METHODS: We retrospectively reviewed the medical records of 92
      patients who underwent liver resection from March 2012 to October 2015. We
      investigated prognostic factors for recurrence and survival. We analyzed the
      correlation of resection margin size and PET positivity. Resection margins were
      classified as less than 1 cm and more than 1 cm. RESULTS: Twenty six (31.3%)
      patients had PET-positive HCC. Multivariate analysis showed PET, satellite
      nodules, microvessel invasion, and multicentric occurrence were significant
      prognostic factors for HCC recurrence. Multivariate analysis also showed
      satellite nodules and microscopic portal vein invasion were significant
      prognostic factors for overall survival (OS). Resection margin size did not
      affect disease-free survival (DFS) (p = 0.681) or OS (p = 0.301) in patients with
      PET-negative HCC, but showed a difference in DFS [<1 cm at 11 months vs. >=1 cm
      at 41 months (p = 0.188)] and OS [<1 cm at 28 months vs. >=1 cm at 48 months (p <
      0.001)] in patients with PET-positive HCC. CONCLUSIONS: PET has low sensitivity
      for HCC. However, it is useful to predict treatment outcomes after liver
      resection or liver transplantation for HCC. Although the extent of liver
      resection must be decided based on liver function, a resection margin size >1 cm
      may improve DFS and OS in patients with PET-positive HCC.

PMID- 29026967
TI  - A rat model of FOLFOX-induced neuropathy: effects of oral dimiracetam in
      comparison with duloxetine and pregabalin.
AB  - BACKGROUND AND AIM: The FOLFOX family of chemotherapy regimens are hampered by
      the development of a painful neuropathy. Current clinical treatments are
      inadequate, and furthermore, the research of innovative drugs is strongly
      disadvantaged by the absence of a preclinical model based on the complete mixture
      of FOLFOX components. The aim of this study was to set up a rat model of FOLFOX
      induced neuropathy in rats, validate its predictability by reference drugs, and
      evaluate the effectiveness of the new anti-neuropathic compound dimiracetam.
      METHODS: Male Sprague-Dawley rats were treated intraperitoneally with the FOLFOX
      components (6 mg kg-1 oxaliplatin, 50 mg kg-1 5-FU, 90 mg kg-1 leucovorin calcium
      salt) or oxaliplatin alone (6 mg kg-1) on days 0, 7, 14, and 21, whereas a
      separate group received one more injection of FOLFOX on day 28. Pain behavioural
      measurements (paw pressure, cold plate, and electronic Von Frey tests) and motor
      coordination (Rota-rod test) were assessed before and after treatments.
      Behavioural, motor, neurological, and autonomic parameters (open field and Irwin
      tests) were evaluated. RESULTS: FOLFOX reduced the pain threshold in response to
      mechanical noxious and thermal (cold) non-noxious stimuli beginning from day 14
      up to day 42 comparably to oxaliplatin alone. A fifth FOLFOX injection enhanced
      the severity but not the duration of painful alterations. Spontaneous activity,
      behavioural, autonomic, and neurological functions were also affected, whereas
      the motor coordination was not altered. On day 22, duloxetine (15 mg kg-1, per
      os), morphine (10 mg kg-1, subcutaneously), or pregabalin (20 mg kg-1, per os),
      acutely administered, reduced the FOLFOX-dependent hypersensitivity. Repeated
      treatments with dimiracetam (150 mg kg-1, per os, twice daily, from day 22)
      significantly protected rats from FOLFOX-induced alterations of pain threshold as
      well as from autonomic and neurological impairments taking effect after 7 days
      treatment. Pregabalin repeatedly administered (20 mg kg-1, per os, twice daily,
      from day 22) was less effective in reducing mechanical hypersensitivity.
      CONCLUSION: A clinically consistent model of FOLFOX-induced neurotoxicity has
      been developed in rats. Dimiracetam fully reduced hypersensitivity and
      neurological alterations showing a relevant profile as anti-neuropathic resource.

PMID- 29026968
TI  - Clinical Outcome, Social Impact and Patient Expectation: a Purposive Sampling
      Pilot Evaluation of Patients in Benin Seven Years After Surgery.
AB  - BACKGROUND: Access to affordable and timely surgery is not equitable around the
      world. Five billion people lack access, and while non-governmental organizations
      (NGOs) help to meet this need, long-term surgical outcomes, social impact or
      patient experience is rarely reported. METHOD: In 2016, Mercy Ships, a surgical
      NGO, undertook an evaluation of patients who had received surgery seven years
      earlier with Mercy Ships in 2009 in Benin. Using purposive sampling, patients who
      had received maxillofacial, plastics or orthopedic surgery were invited to attend
      a surgical evaluation day. In this pilot study, we used semi-structured
      interviews and questionnaire responses to assess patient expectation, surgical
      and social outcome. RESULTS: Our results show that seven years after surgery 35%
      of patients report surgery-related pain and 18% had sought further care for a
      clinical complication of their condition. However, 73% of patients report gaining
      social benefit from surgery, and overall patient satisfaction was 89%, despite
      35% of patients saying that they were unclear what to expect after surgery
      indicating a mismatch of doctor/patient expectations and failure of the consent
      process. CONCLUSION: In conclusion, our pilot study shows that NGO surgery in
      Benin provided positive social impact associated with complication rates
      comparable to high-income countries when assessed seven years later. Key areas
      for further study in LMICs are: evaluation and treatment of chronic pain, consent
      and access to further care.

PMID- 29026969
TI  - Extended Serum Lipid Profile Predicting Long-Term Survival in Patients Treated
      for Abdominal Aortic Aneurysms.
AB  - BACKGROUND: Individuals treated for abdominal aortic aneurysms (AAAs) are high
      risk patients in whom better risk prediction could improve survival. Contemporary
      serum lipid parameters, such as apolipoproteins and lipoprotein subfractions, may
      improve or complement the prognostic value of traditional serum lipids. The aim
      of this study was to ascertain the extended serum lipid profiles, long-term
      prognosis and their association in AAA patients. METHODS: Altogether 498 patients
      treated for AAAs and with available serum lipid values were retrospectively
      analysed. Contemporary lipid parameters were estimated using a neural network
      model, the extended Friedewald formula. RESULTS: Younger age, smoking and urgent
      or emergency surgery were associated with an unfavourable, and coronary disease
      and previous stroke with a favourable lipid profile. In multivariable analysis-in
      addition to advanced age, aneurysm rupture, smoking, pulmonary disease and
      diabetes-high triglycerides and traditional LDL cholesterol were significant
      independent risk factors for mortality, HR 1.84 (95% CI 1.20-2.81) and 1.79 (95%
      CI 1.18-2.73), respectively, while higher EFW-IDL cholesterol was associated with
      better survival, HR 0.31 (95% CI 0.19-0.65). Including serum lipid parameters
      improved the prediction of 5-year survival (NRI = 17.7%, p = 0.016). CONCLUSIONS:
      Extended serum lipid parameters complement risk prediction of patients treated
      for AAAs. An unfavourable lipid profile is associated with treatment of AAA
      earlier in life and with inferior long-term survival.

PMID- 29026970
TI  - Determination of the Amount of Ptosis Correction in Levator Resection Surgery for
      Pediatric Congenital Ptosis.
AB  - BACKGROUND: It is difficult to determine the amount of eyelid lift in levator
      resection surgery for congenital ptosis, especially when the surgery is performed
      under general anesthesia. We aim to introduce an objective and steady method with
      which to adjust eyelid height, and to identify other factors to be considered
      during surgery. METHODS: This is a retrospective, observational study of 110 eyes
      from 78 patients who underwent levator resection surgery for congenital ptosis.
      Postoperative eyelid height was observed chronologically. The amount of eyelid
      lift during surgery was compared with the real postoperative change of palpebral
      fissure width (PF). The factors influencing the postoperative changes in eyelid
      height were investigated to predict outcome. RESULTS: Postoperative eyelid height
      stabilized 1 month after surgery. The real postoperative change in PF was
      slightly larger than the amount of intraoperative eyelid lift in cases with
      levator muscle function (LF) >= 7 mm, whereas it tended to be smaller in cases
      with LF < 5 mm. Statistically significant factors influencing the difference
      between the amount of intraoperative eyelid lift and the real postoperative
      change of eyelid height included preoperative PF, preoperative LF, and anesthesia
      induced lagophthalmos. CONCLUSION: The preoperative PF, preoperative LF, and
      anesthesia-induced lagophthalmos should be considered when determining the amount
      of ptosis correction to perform in levator resection surgery. LEVEL OF EVIDENCE
      IV: This journal requires that authors assign a level of evidence to each
      article. For a full description of these Evidence-Based Medicine ratings, please
      refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 29026971
TI  - Is impaired cerebral vasoreactivity an early marker of cognitive decline in
      multiple sclerosis patients?
AB  - OBJECTIVE: The link between cerebral vasoreactivity and cognitive status in
      multiple sclerosis remains unclear. The aim of the present study was to
      investigate a potential decrease of cerebral vasoreactivity in multiple sclerosis
      patients and correlate it with cognitive status. METHODS: Thirty-three patients
      with multiple sclerosis (nine progressive and 24 remitting forms, median age: 39
      years, 12 males) and 22 controls underwent MRI with a hypercapnic challenge to
      assess cerebral vasoreactivity and a neuropsychological assessment. Cerebral
      vasoreactivity, measured as the cerebral blood flow percent increase normalised
      by end-tidal carbon dioxide variation, was assessed globally and by regions of
      interest using the blood oxygen level-dependent technique. Non-parametric
      statistics tests were used to assess differences between groups, and associations
      were estimated using linear models. RESULTS: Cerebral vasoreactivity was lower in
      patients with cognitive impairment than in cognitively normal patients (p=0.004)
      and was associated with education level in patients (R2 = 0.35; p = 0.047). There
      was no decrease in cerebral vasoreactivity between patients and controls.
      CONCLUSIONS: Cognitive impairment in multiple sclerosis may be mediated through
      decreased cerebral vasoreactivity. Cerebral vasoreactivity could therefore be
      considered as a marker of cognitive decline in multiple sclerosis. KEY POINTS: *
      Cerebral vasoreactivity does not differ between multiple sclerosis patients and
      controls. * Cerebral vasoreactivity measure is linked to cognitive impairment in
      multiple sclerosis. * Cerebral vasoreactivity is linked to level of education in
      multiple sclerosis.

PMID- 29026972
TI  - Retroperitoneal lymph node dissection for testicular seminomas: population-based
      practice and survival outcomes.
AB  - PURPOSE: While retroperitoneal lymph node dissection (RPLND) is traditionally
      reserved for nonseminomatous germ cell tumors, recent efforts to reduce long-term
      toxicities of radiation and chemotherapy have turned attention to its application
      for testicular seminomas. Currently, RPLND is reserved for the post-chemotherapy
      for stage II testicular seminomas; we aimed to describe current utilization of
      RPNLD for testicular seminomas by stage and implications for survival. METHODS: A
      national sample of men diagnosed with stage IA/IB/IS/IIA/IIB/IIC testicular
      seminoma (1988-2013) was evaluated from SEER Program registries. Stage-specific
      utilization of RPLND was determined. Cox proportional hazards models, adjusted
      for age, race, and radiotherapy, evaluated overall (OS) and cancer-specific
      survival (CSS) for the RPLND cohort. Adjusted models assessed predictors of
      RPLND. RESULTS: A total of 17,681 men (mean age 38.1 years) with testicular
      seminoma were included with low utilization of RPLND for stage I disease (1.3%
      overall) and higher rates for stage II disease (10.6% overall). There were no
      appreciable trends over time. Patients receiving RPLND did not appear to have
      worse OS or CSS on adjusted stage-by-stage analysis. Higher stage disease (IIA
      IIC) was associated with greater need for RPLND while radiotherapy was associated
      with decreased use [OR 0.40 (0.32-0.51), p < 0.001]. CONCLUSIONS: Utilization of
      RPLND for testicular seminomas in the post-chemotherapy setting has remained
      stable over a 25-year period. Patients undergoing RPLND are a higher risk cohort
      but stage-by-stage survival outcomes appeared comparable to men not undergoing
      RPLND. Upcoming trials implementing RPLND as a first-line modality for testicular
      seminoma or isolated retroperitoneal relapse will help better quantify relative
      recurrence and survival.

PMID- 29026973
TI  - Active DNA demethylation: mechanism and role in plant development.
AB  - Active DNA demethylation (enzymatic removal of methylated cytosine) regulates
      many plant developmental processes. In Arabidopsis, active DNA demethylation
      entails the base excision repair pathway initiated by the Repressor of silencing
      1/Demeter family of bifunctional DNA glycosylases. In this review, we first
      present an introduction to the recent advances in our understanding about the
      mechanisms of active DNA demethylation. We then focus on the role of active DNA
      demethylation in diverse developmental processes in various plant species,
      including the regulation of seed development, pollen tube formation, stomatal
      development, fruit ripening, and nodule development. Finally, we discuss future
      directions of research in the area of active DNA demethylation.

PMID- 29026974
TI  - Pheochromocytoma as a frequent false-positive in adrenal washout CT: A systematic
      review and meta-analysis.
AB  - OBJECTIVE: To evaluate the proportion of pheochromocytomas meeting the criteria
      for adenoma on adrenal washout CT and the diagnostic performance of adrenal
      washout CT for differentiating adenoma from pheochromocytoma. METHODS: MEDLINE
      and EMBASE were searched to 28 March 2017. We included studies that used adrenal
      washout CT for characterisation of pheochromocytomas. Two independent reviewers
      assessed the methodological quality using Quality Assessment of Diagnostic
      Accuracy Studies-2. Proportions were pooled using an inverse variance method for
      calculating weights (random-effects). Sensitivity and specificity were pooled
      using hierarchical logistic regression modelling and plotted in a hierarchical
      summary receiver-operating-characteristics (HSROC) plot. RESULTS: Ten studies
      (114 pheochromocytomas) were included. The pooled proportion of pheochromocytomas
      meeting the criteria for adenomas was 35 % (95 % CI 20-51). For eight studies
      providing information on diagnostic performance, the pooled sensitivity and
      specificity for differentiating adenoma from pheochromocytoma were 0.97 (95 % CI
      0.93-0.99) and 0.67 (95 % CI 0.44-0.84), respectively. The area under the HSROC
      curve was 0.97 (95 % CI 0.95-0.98). CONCLUSIONS: There was a non-negligible
      proportion of pheochromocytomas meeting the criteria for adenoma on adrenal
      washout CT. Although overall diagnostic performance was excellent for
      differentiating adenoma from pheochromocytoma, specificity was relatively low.
      KEY POINTS: * Non-negligible proportion of pheochromocytomas can be mistaken for
      adenoma. * Adrenal washout CT showed good sensitivity (97%) but relatively low
      specificity (67%). * Findings other than washout percentage should be used when
      diagnosing pheochromocytomas.

PMID- 29026975
TI  - Effect of isoliquiritigenin for the treatment of atopic dermatitis-like skin
      lesions in mice.
AB  - Atopic dermatitis (AD) is a common chronic inflammatory skin disease
      characterized with high heterogeneity. Recent studies have suggested that it is
      driven by both terminal keratinocyte differentiation defects and type 2 immune
      responses. The mainstay steroid topical therapy has severe side effect and new
      treatment is in demand. Isoliquiritigenin (ISLG) is a small phenolic bioactive
      molecule from licorice that has shown multiple pharmacological effects against
      cancer, inflammatory disorder, and cardiovascular diseases. ISLG was evaluated in
      AD-like lesion model induced by the repetitive application of 2,4
      dinitrochlorobenzene (DNCB) in BALB/c mice. Overall symptom score, serological
      and molecular changes of the skin lesions were evaluated. ISLG could ameliorate
      the overall manifestation of AD-like symptoms including scratching behavior
      incidence and skin lesion severity. At blood level, ISLG significantly suppressed
      the DNCB-induced IgE and Th2 cytokines up-regulation. At skin lesion site, ISLG
      also inhibited DNCB-induced pro-inflammatory cytokines like TNF-alpha, IL-6 as
      well as IL-4 expressions. In a human monocyte model THP-1, ISLG suppressed the up
      regulation of CD86 and CD54 and abolished the DNCB-induced p38-alpha and ERK
      activation, suggesting a molecular mechanism for ISLG therapy. This study
      indicated that ISLG could be a potential therapeutic agent for the treatment of
      AD.

PMID- 29026978
TI  - Enigma of scapular foramen and tunnels: an untold story.
AB  - PURPOSE: The study was undertaken to make a qualitative and quantitative
      assessment of unnamed foramen and tunnels in adult human scapulae with aid of
      plain and contrast radiographs. MATERIALS AND METHODS: A total of 120 dry bones,
      60 each of the right and the left side were included in the study. Distribution
      of these foramina and tunnels was noted for their number, side, location, course
      and communication. Their morphometry was done using Vernier's caliper. RESULTS:
      Incidence of scapular foramina was 7.5% (R > L), whereas scapular tunnels were
      seen in 15.8% cases. Incidence of the sinuous, curved, and straight tunnels was
      found to be 50, 39, and 10.7% respectively. Left-sided tunnels were longer than
      the right ones. Plain and contrast radiographs were taken to confirm the
      findings. CONCLUSION: Anatomy literature describes only two scapular foramina,
      namely, nutrient foramen and suprascapular foramen/notch in a great zeal;
      occurrence of such anonymous foramina is hardly discussed. Through this study,
      there is an endeavor towards unfolding the mystery of scapular foramina in terms
      of their morphometry and distribution, the knowledge of which will aid
      clinicians, forensic experts, and surgeons in better diagnosis and management of
      clinical cases.

PMID- 29026979
TI  - HPAEC-PAD for oligosaccharide analysis-novel insights into analyte sensitivity
      and response stability.
AB  - The rising importance of accurately detecting oligosaccharides in biomass
      hydrolyzates or as ingredients in food, such as in beverages and infant milk
      products, demands for the availability of tools to sensitively analyze the broad
      range of available oligosaccharides. Over the last decades, HPAEC-PAD has been
      developed into one of the major technologies for this task and represents a
      popular alternative to state-of-the-art LC-MS oligosaccharide analysis. This work
      presents the first comprehensive study which gives an overview of the separation
      of 38 analytes as well as enzymatic hydrolyzates of six different polysaccharides
      focusing on oligosaccharides. The high sensitivity of the PAD comes at cost of
      its stability due to recession of the gold electrode. By an in-depth analysis of
      the sensitivity drop over time for 35 analytes, including xylo- (XOS),
      arabinoxylo- (AXOS), laminari- (LOS), manno- (MOS), glucomanno- (GMOS), and
      cellooligosaccharides (COS), we developed an analyte-specific one-phase decay
      model for this effect over time. Using this model resulted in significantly
      improved data normalization when using an internal standard. Our results thereby
      allow a quantification approach which takes the inevitable and analyte-specific
      PAD response drop into account. Graphical abstract HPAEC-PAD analysis of
      oligosaccharides and determination of PAD response drop leading to an improved
      data normalization.

PMID- 29026977
TI  - Mesh Versus Patch Repair for Epigastric and Umbilical Hernia (MORPHEUS Trial);
      One-Year Results of a Randomized Controlled Trial.
AB  - DESIGN: This trial is a randomized controlled, patient-blinded, multicentre,
      superiority trial. METHODS: All patients >=18 years with a single, symptomatic
      and primary umbilical or epigastric hernia (<2 fingers) qualified for
      participation in the study. Flat polypropylene mesh repair was compared to patch
      repair (PROCEED(r) Ventral Patch) (PVP). The objective of this trial was to
      identify a superior method for umbilical and epigastric hernia repair in terms of
      complication rates. RESULTS: A total of 352 patients were randomized in this
      trial; 348 patients received the intervention (n = 177 PVP vs. n = 171 mesh). No
      peri-operative complications occurred. PVP placement was significantly faster
      compared to mesh placement (30 min, SD 11 vs. 35 min, SD 11) and was scored as an
      easier procedure. At 1-month follow-up, 76 patients suffered any kind of
      complication. There was no significant difference in the proportion of
      complications (24.9% for PVP and 18.7% for mesh, p = 0.195). A significant
      difference was seen in re-operation rate within 1 month, significantly less early
      re-operations in the mesh group (0.0 vs. 2.8%, p = 0.027). After 1-year follow
      up, no significant differences are seen in recurrence rates (n = 13, 7.8% PVP vs.
      n = 5, 3.3% mesh, p = 0.08). CONCLUSIONS: Both mesh and PVP had a comparable
      amount of reported complications. There was a significantly higher incidence of
      early re-operations due to early complications in the PVP group. No differences
      were seen in infection rates and the need for antibiotic treatment. No
      significant difference was seen in the recurrence rates. REGISTRATION: This trial
      was registered in the Dutch Trail Registry (NTR) NTR2514NL33995.060.10. [12].

PMID- 29026981
TI  - A clinical scoring system to predict the development of intraventricular
      hemorrhage (IVH) in premature infants.
AB  - : OBJECTiVE: The aim of this study is to develop a scoring system for the
      prediction of intraventricular hemorrhage (IVH) in preterm infants in the first 7
      days of life. METHODS: A prospective, clinical study was conducted in Bahcesehir
      University, Medical Park Goztepe Hospital Neonatal Intensive Care Unit, with the
      enrollment of 144 preterm infants with gestational age between 24 and 34 weeks.
      All preterms were followed up for IVH after birth until the 4th week of life. The
      demographic characteristics and clinical risk factors were noted. Risk factors
      were analyzed. The score was established after logistic regression analysis,
      considering the impact of each variable on the occurrence of IVH within the first
      7 days of life. The IVH scores were further applied prospectively to 89 preterm
      infants as validation cohort. RESULTS: Low gestational age (GA), low Apgar score,
      and having bleeding diathesis were the most important risk factors for IVH.
      According to these risk factors, a scoring system was developed for IVH ranged
      from 0 to 5. According to the risk ratios (RR) obtained from the logistic
      regression model, low GA (<= 28 gestational week), presence of bleeding diathesis
      within 7 days, and low Apgar score increased the risk of IVH (RR = 3.32 for GA <=
      28 gestational week, RR = 6.7 for presence of bleeding diathesis in 7th day, RR =
      3 for having low Apgar score). The score was validated successfully in 89
      infants. The area under ROC curve was 0.85 for derivation cohort and 0.807 for
      validation cohort. The predictive ability of the IVH score for derivation and
      validation cohort was calculated. The negative predictive values of a score less
      than 4 were 96.4 and 59.1%. CONCLUSiON: Concerning IVH-related sequelae which
      continue to be a major public health problem, we have developed a feasible
      predictive model for evaluating the risk for developing IVH for preterm infants
      in the first 7 days of life.

PMID- 29026980
TI  - Evolution of the androgen-induced male phenotype.
AB  - The masculine reproductive phenotype varies significantly across vertebrates. As
      a result, biologists have long recognized that many of the mechanisms that
      support these phenotypes-particularly the androgenic system-is evolutionarily
      labile, and thus susceptible to the effects of selection for different traits.
      However, exactly how androgenic signaling systems vary in a way which results in
      dramatically different functional outputs, remain largely unclear. We explore
      this topic here by outlining four key-but non-mutually exclusive-hypotheses that
      propose how the mechanisms of androgenic signaling might change over time to
      potentiate the emergence of phenotypical variation in masculine behavior and
      physiology. We anchor this framework in a review of our own studies of a tropical
      bird called the golden-collared manakin (Manacus vitellinus), which has evolved
      an exaggerated acrobatic courtship display that is heavily androgen-dependent.
      The result is an example of how the cellular basis of androgenic action can be
      modified to support a unique reproductive repertoire. We end this review by
      highlighting a broad pathway forward to further pursue the intricate ways by
      which the mechanisms of hormone action evolve to support processes of adaptation
      and animal design.

PMID- 29026982
TI  - Severe Hemoptysis Associated with Bacterial Pulmonary Infection: Clinical
      Features, Significance of Parenchymal Necrosis, and Outcome.
AB  - PURPOSE: Severe hemoptysis (SH) associated with non-tuberculosis bacterial lower
      respiratory tract infection (LRTI) is poorly described, and the efficacy of the
      usual decision-making process is unknown. This study aimed at describing the
      clinical, radiological patterns, mechanism, and microbiological spectrum of SH
      related to bacterial LRTI, and assessing whether the severity of hemoptysis and
      the results of usual therapeutic strategy are influenced by the presence of
      parenchymal necrosis. METHODS: A single-center analysis of patients with SH
      related to bacterial LRTI from a prospective registry of consecutive patients
      with SH admitted to the intensive care unit of a tertiary referral center between
      November 1996 and May 2013. RESULTS: Of 1504 patients with SH during the study
      period, 65 (4.3%) had SH related to bacterial LRTI, including non-necrotizing
      infections (n = 31), necrotizing pneumonia (n = 23), pulmonary abscess (n = 10),
      and excavated nodule (n = 1). The presence of parenchymal necrosis (n = 34, 52%)
      was associated with a more abundant bleeding (volume: 200 ml [70-300] vs. 80 ml
      [30-170]; p = 0.01) and a more frequent need for endovascular procedure (26/34;
      76% vs. 9/31; 29%; p < 0.001). Additionally, in case of parenchymal necrosis, the
      pulmonary artery vasculature was involved in 16 patients (47%), and the failure
      rate of endovascular treatment was up to 25% despite multiple procedures.
      CONCLUSIONS: Bacterial LRTI is a rare cause of SH. The presence of parenchymal
      necrosis is more likely associated with bleeding severity, pulmonary vasculature
      involvement, and endovascular treatment failure.

PMID- 29026976
TI  - Reductive evolution of chloroplasts in non-photosynthetic plants, algae and
      protists.
AB  - Chloroplasts are generally known as eukaryotic organelles whose main function is
      photosynthesis. They perform other functions, however, such as synthesizing
      isoprenoids, fatty acids, heme, iron sulphur clusters and other essential
      compounds. In non-photosynthetic lineages that possess plastids, the chloroplast
      genomes have been reduced and most (or all) photosynthetic genes have been lost.
      Consequently, non-photosynthetic plastids have also been reduced structurally.
      Some of these non-photosynthetic or "cryptic" plastids were overlooked or
      unrecognized for decades. The number of complete plastid genome sequences and/or
      transcriptomes from non-photosynthetic taxa possessing plastids is rapidly
      increasing, thus allowing prediction of the functions of non-photosynthetic
      plastids in various eukaryotic lineages. In some non-photosynthetic eukaryotes
      with photosynthetic ancestors, no traces of plastid genomes or of plastids have
      been found, suggesting that they have lost the genomes or plastids completely.
      This review summarizes current knowledge of non-photosynthetic plastids, their
      genomes, structures and potential functions in free-living and parasitic plants,
      algae and protists. We introduce a model for the order of plastid gene losses
      which combines models proposed earlier for land plants with the patterns of gene
      retention and loss observed in protists. The rare cases of plastid genome loss
      and complete plastid loss are also discussed.

PMID- 29026983
TI  - Quartz crystal microbalance as an assay to detect anti-drug antibodies for the
      immunogenicity assessment of therapeutic biologics.
AB  - Because of their biological origins, therapeutic biologics can trigger an
      unwanted deleterious immune response with some patients. The immunogenicity of
      therapeutic biologics can affect drug efficacy and patient safety by the
      production of circulating anti-drug antibodies (ADA). In this study, quartz
      crystal microbalance (QCM) was developed as an assay to detect ADA. Etanercept
      (Enbrel(r)) was covalently grafted to dextran-modified QCM surfaces. Rabbits were
      immunized with etanercept to generate ADA. Results showed the QCM assay could
      detect purified ADA from rabbits at concentrations as low as 50 ng/mL, within the
      sensitivity range of ELISA. The QCM assay could also assess the ADA isotype. It
      was shown that the ADA were composed of the IgG isotype, but not IgM, as
      expected. Furthermore, it was shown that QCM surfaces that had been used to
      detect ADA could be regenerated in glycine-HCl solution and reused. The QCM assay
      was also demonstrated to detect ADA in crude serum samples. Serum was collected
      from the rabbits and analyzed before and after etanercept immunization. ADA were
      clearly detected in serum from rabbits after immunization, but not in serum
      before immunization. Serum from patients administered with etanercept for
      rheumatoid arthritis (RA) treatment was also analyzed and compared to serum from
      healthy donors. Sera from 10 RA patients were analyzed. Results showed one of the
      RA patient serum samples may have ADA present. In conclusion, QCM appears to be a
      viable assay to detect ADA for the immunogenicity assessment of therapeutic
      biologics.

PMID- 29026985
TI  - Deep lobe parotidectomy-why, when, and how?
AB  - This editorial explores the controversies concerning the surgical management of
      the deep portion of the parotid gland. Specifically, when should the parotid deep
      lobe be removed if there is metastatic cancer to a superficial parotid node or
      when a primary aggressive cancer is found in the superficial lobe? The
      background, indications, rationale, and results of removing the deep lobe nodes
      are reviewed. Removal of the deep lobe is done to optimize the oncologic outcome
      for the patient. Deep lobe parotidectomy plays an important role in the treatment
      of many parotid gland malignancies.

PMID- 29026986
TI  - Inter-individual differences in decision-making, flexible and goal-directed
      behaviors: novel insights within the prefronto-striatal networks.
AB  - Inflexible behavior is a hallmark of several decision-making-related disorders
      such as ADHD and addiction. As in humans, a subset of healthy rats makes poor
      decisions and prefers immediate larger rewards despite suffering large losses in
      a rat gambling task (RGT). They also display a combination of traits reminiscent
      of addiction, notably inflexible behavior and perseverative responses. The goal
      of the present work was twofold: (1) to elucidate if behavioral inflexibility of
      poor decision-makers could be related to a lower quality of goal-directed
      behavior (action-outcome associations); (2) to uncover the neural basis of inter
      individual differences in goal-directed behavior. We specifically assessed inter
      individual differences in decision-making in the RGT, flexibility in the RGT
      reversed version and goal-directed behavior in a contingency degradation test,
      i.e., response adaptation when dissociating reward delivery from the animal's
      action. The contributions of the medial prefrontal cortex and the dorsal striatum
      to action-outcome associations were assessed using Zif268 immunodetection.
      Inflexible behavior was related to a lower sensitivity to contingency degradation
      in all poor decision-makers and only in a few good decision-makers. This poorer
      sensitivity was associated with a lower immunoreactivity in prelimbic and
      infralimbic cortices and a higher one in the dorsomedial and dorsolateral
      striatum. These findings suggest that an imbalanced prefronto-striatal activity
      could underlie inaccurate goal representation in changing environments and may
      promote maladaptive habit formation among poor decision-makers. These data
      strengthen our previous work identifying biomarkers of vulnerability to develop
      psychiatric disorders and demonstrate the relevance of inter-individual
      differences to model maladaptive behaviors.

PMID- 29026984
TI  - Flooding Duration Affects the Structure of Terrestrial and Aquatic Microbial
      Eukaryotic Communities.
AB  - The increasing number and duration of inundations is reported to be a consequence
      of climate change and may severely compromise non-adapted macroorganisms. The
      effect of flooding events on terrestrial and aquatic microbial communities is,
      however, less well understood. They may respond to the changed abiotic properties
      of their native habitat, and the native community may change due to the
      introduction of alien species. We designed an experiment to investigate the
      effect of five different flooding durations on the terrestrial and aquatic
      communities of eukaryotic microorganism, using the AquaFlow mesocosms. With
      amplicon sequencing of the small subunit (SSU) and internal transcribed spacer
      (ITS) rRNA gene regions, we analyzed community compositions directly before and
      after flooding. Subsequently, they were monitored for another 28 days, to
      determine the sustainability of community changes. Our results revealed a
      temporary increase in similarity between terrestrial and aquatic communities
      according to OTU composition (operational taxonomic unit, serves as a proxy for
      species). Increased similarity was mainly caused by the transmission of OTUs from
      water to soil. A minority of these were able to persist in soil until the end of
      the experiment. By contrast, the vast majority of soil OTUs was not transmitted
      to water. Flooding duration affected the community structure (abundance) more
      than composition (occurrence). Terrestrial communities responded immediately to
      flooding and the flooding duration influenced the community changes. Independent
      from flooding duration, all terrestrial communities recovered largely after
      flooding, indicating a remarkable resilience to the applied disturbances. Aquatic
      communities responded immediately to the applied inundations too. At the end of
      the experiment, they grouped according to the applied flooding duration and the
      amount of ammonium and chloride that leached from the soil. This indicates a
      sustained long-term response of the aquatic communities to flooding events.

PMID- 29026988
TI  - Pulmonary annular motion velocity reflects right ventricular outflow tract
      function in children with surgically repaired congenital heart disease.
AB  - Right ventricular (RV) dysfunction is generally evaluated using analyses of
      tricuspid annular motion. However, it represents only one aspect of RV
      performance. Whether measuring pulmonary annular motion velocity could serve as a
      novel way to evaluate global RV and/or RV outflow tract (RVOT) performance in
      pediatric congenital heart disease (CHD) patients with surgically repaired RVOT
      was evaluated. In this prospective study, tissue Doppler-derived pulmonary
      annular motion velocity was measured in children (aged 2-5 years) with RVOT
      reconstruction (RVOTR group, n = 48) and age-matched healthy children (Control, n
      = 60). The types of RVOTR procedures were as follows: pulmonary valve-sparing
      procedure (PVS, n = 7); transannular patch with monocusp valve reconstruction
      (TAP, n = 29); and RV-to-PA conduit reconstruction using a pericardial valve with
      expanded polytetrafluoroethylene conduit (Rastelli, n = 12). Pulmonary annular
      motion velocity waveforms comprised systolic bimodal (s1' and s2') and diastolic
      e' and a' waves in all participants. The peak velocities of s1', s2', e', and a'
      were significantly lower in the RVOTR group than in the control group (all p <
      0.0001). Furthermore, these parameters depended significantly on the type of
      surgical procedure. The peak velocities of s1', s2', and e' had significant
      correlations with RVOT ejection fraction (RVOT-EF) (r = 0.56, 0.49, and 0.34,
      respectively), and RVOT fractional shortening (RVOT-FS) (r = 0.72, 0.55, and
      0.41, respectively), although there were no significant correlations between
      pulmonary annular motion and global RV function, including RV ejection fraction
      (RVEF) and RV fractional area change (RVFAC) in the assessment of all RVOTR group
      patients. The pulmonary annular motion parameters in the PVS group had
      significant correlations with both global RV and RVOT performance. The TAP group
      showed significant correlations between RVOT function and pulmonary annular
      motion. The Rastelli group showed almost no significant correlations between
      RV/RVOT function and tissue Doppler parameters. Pulmonary annular motion velocity
      is a simple, rapid, reproducible, and useful method of assessing RVOT function in
      children with surgically repaired CHD.

PMID- 29026987
TI  - Acetylcholinesterase activity and time after a peak pesticide-use period among
      Ecuadorian children.
AB  - PURPOSE: Mother's Day (May) is a holiday with substantial demand for flowers,
      associated with heightened flower production and escalated pesticide use. The
      effect of spray seasons on pesticide exposures of children living in agricultural
      communities but who do not work in agriculture is poorly understood. In this
      study, we estimated the association of time after Mother's Day harvest with
      children's acetylcholinesterase (AChE) activity. AChE is a physiological marker
      of organophosphate/carbamate pesticide exposures that may take up to 3 months to
      normalize after its inhibition. METHODS: We examined 308 children, aged 4-9
      years, in Ecuadorian agricultural communities during a low flower-production
      season but within 63-100 days (mean: 81.5 days, SD: 10.9) after Mother's Day
      harvest. We quantified AChE activity (mean: 3.14 U/mL, SD: 0.49) from a single
      finger-stick sample. RESULTS: We observed positive linear associations between
      time after the harvest and AChE among participants living near plantations. The
      associations were strongest among participants living within 233 m [(0.15 U/mL
      (95% CI 0.02, 0.28)], slightly weaker among participants living within 234-532 m
      [0.11 U/mL (0.00, 0.23)], and not associated among participants at greater
      distances. Similar findings were observed across categories of areas of flower
      plantations within 500 m of homes. CONCLUSIONS: These cross-sectional findings
      suggest that a peak pesticide-use period can decrease AChE activity of children
      living near plantations. These seasonal pesticide exposures could induce short-
      and long-term developmental alterations in children. Studies assessing exposures
      at multiple times in relation to pesticide spray seasons among children who do
      not work in agriculture are needed.

PMID- 29026989
TI  - The pattern, peculiarities, and management challenges of spina bifida in a
      teaching hospital in Southwest Nigeria.
AB  - PURPOSE: Spina bifida is a common congenital anomaly of the nervous system. It is
      frequently associated with significant morbidity and sometimes mortality in
      affected children. In this paper, we review the clinico-epidemiological pattern,
      peculiarities, and therapeutic challenges of this condition in our practice
      setting. METHODS: This is a retrospective study of all cases of spina bifida
      managed from July 2000 to March 2016 at a tertiary health facility located in the
      southwest region of Nigeria. Relevant information was retrieved from the medical
      records. The data was collected using a pro forma and analyzed with SPSS version
      22. RESULTS: Data from 148 patients was reviewed and analyzed. There were 78
      males and 70 females. Only 5.8% of these children were delivered at the health
      institution. A fifth (20%) of the patients were first born of their mothers. The
      mean maternal age was 29 years. Few (10.1%) mothers use folate medication prior
      to conception and only 58% of the mothers use folate during antenatal care. Mean
      duration of pregnancy was 38 weeks. The most common anatomical site was
      lumbosacral region (74.3%) while the most common pathology was myelomeningocele
      80.4%. Mean age at surgery was 88.68 h. Mean duration of surgery was 92.8 min.
      Mean follow-up duration was 46.8 weeks. As many as 59% of the patients had some
      neurologic improvement noticed during follow-up clinic visits. CONCLUSION: Spina
      bifida occurs frequently in our environment. Low socio-economic status and poor
      antenatal clinic visits contributes significantly to its occurrence.

PMID- 29026990
TI  - Are exon 19 deletions and L858R different in early stage lung adenocarcinoma?
AB  - INTRODUCTION: Evidence shows that exon 19 deletions (19del) and exon 21 Leu858Arg
      point mutation (L858R) of EGFR are different in response to EGFR tyrosine kinase
      inhibitor (EGFR-TKI) therapy in advanced lung cancers. However, the impact of the
      two mutational types in the early stage lung adenocarcinoma is unknown. METHODS:
      We enrolled consecutive patients with operable adenocarcinoma which harbored
      19del or L858R to investigate the clinicopathologic characteristics and
      prognostic outcomes. RESULTS: Between 2008 and 2013, a total of 607 patients with
      19del (47.9%) or L858R (52.1%) were included in this study. Clinicopathologic and
      disease-associated factors were well-balanced between 19del and L858R patients.
      Both recurrence-free survival (5-year RFS: 37.9% vs. 42.9%, p = 0.075) and
      overall survival (5-year OS: 64.7% vs. 60.7%, p = 0.741) were similar between the
      two groups. After relapse, 19del was associated with a better post-recurrence
      survival (PRS) than L858R (p = 0.016). Multivariate analysis demonstrated that
      mutational types (HR = 1.521, 95% CI: 1.106-2.093, p = 0.01) and tyrosine kinase
      inhibitors (TKI) use after recurrence (HR = 0.422, 95% CI: 0.301-0.592, p <
      0.001) were independent predictors of PRS. The 19del and L858R patients were
      similar regarding recurrent patterns, except on pleural/chest wall metastasis
      (26.0% vs. 12.2%, p = 0.007). CONCLUSIONS: Patients with the early stage lung
      adenocarcinoma harboring either 19del or L858R share similar RFS and OS. After
      recurrence, both could benefit from TKI therapy without the need for a second
      biopsy, but 19del seemed to be associated with better PRS.

PMID- 29026991
TI  - Trichomonas vaginalis clinical isolates: cytoadherence and adherence to
      polystyrene, intrauterine device, and vaginal ring.
AB  - The parasitism by Trichomonas vaginalis is complex and in part is mediated by
      cytoadherence accomplished via five surface proteins named adhesins and a
      glycoconjugate called lipophosphoglycan (TvLPG). In this study, we evaluated the
      ability of T. vaginalis isolates to adhere to cells, plastic (polystyrene
      microplates), intrauterine device (IUD), and vaginal ring. Of 32 T. vaginalis
      isolates, 4 (12.5%) were strong adherent. The T. vaginalis isolates TV-LACM6 and
      TV-LACM14 (strong polystyrene-adherent) were also able to adhere to IUD and
      vaginal ring. Following chemical treatments, results demonstrated that the T.
      vaginalis components, lipophosphoglycan, cytoskeletal proteins, and surface
      molecules, were involved in both adherence to polystyrene and cytoadherence. The
      gene expression level from four adhesion proteins was highest in trophozoites
      adhered to cells than trophozoites adhered to the abiotic surface (polystyrene
      microplate). Our data indicate the major involvement of TvLPG in adherence to
      polystyrene, and that adhesins are important for cytoadherence. Furthermore, to
      our knowledge, this is the first report showing the T. vaginalis adherence to
      contraceptive devices, reaffirming its importance as pathogen among women in
      reproductive age.

PMID- 29026992
TI  - Acetabular reconstruction with the Kerboull-type plate at mid-term follow-up:
      survivorship analysis and prognostic factors for loosening.
AB  - INTRODUCTION: Successful reconstruction during total hip arthroplasty for
      acetabular bone defects remains challenging. The purpose of our study was to
      evaluate clinical and radiographic results and performed a survivorship analysis
      for patients with acetabular bone loss undergoing total hip arthroplasty (THA) or
      revision THA using Kerboull-type acetabular reinforcement device(KT plate).
      Additionally, some independent prognostic factors for radiographic failure were
      identified. METHODS: A retrospective cohort study was conducted. Thirty patients
      (36 hips) were available for follow-up examination between 1997 and 2012, with a
      mean follow-up period of 10 years. We evaluated clinical and radiographic
      results. The mean patient age at the time of the operation was 66 years. RESULTS:
      Failure occurred in 6 cases, and further revisions were required for 2 hips. With
      failure for any reason as an endpoint, the cumulative survival at 10 years was
      85%. Survival analysis at 10 years with failure as the endpoint revealed that the
      inclination angle of the KT plate <= 45 degrees  group showed higher survivorship
      than the inclination angle > 45 degrees  group (95.8 vs. 63.6%, P = 0.0047).
      CONCLUSIONS: With a mean follow-up of 10 years, the clinical and radiographic
      outcomes were satisfactory. While this study group was small, the results suggest
      that prosthesis longevity may be improved by setting the inclination angle of
      this reinforcement device at <= 45 degrees .

PMID- 29026994
TI  - The role of phasic norepinephrine modulations during task switching: evidence for
      specific effects in parietal areas.
AB  - Cognitive flexibility is a major requirement for successful goal-directed
      behavior and their neurobiological underpinnings are becoming better understood.
      However, the role of the norepinephrine system during task switching is largely
      enigmatic, despite neurobiological considerations make it likely that the
      norepinephrine system likely plays an important role. Theoretical considerations
      also suggest that the norepinephrine system mainly modulates task-switching
      processes when these rely upon working memory mechanisms. This topic was examined
      in the current system neurophysiological study integrating event-related
      potential (ERP) with pupil diameter data as a proximate the norepinephrine system
      activity. Combined with source localization methods, human brain structure, brain
      function, and phasic modulations by an important neurobiological system were
      integrated. The results show that cognitive-neurophysiological subprocesses
      during the actual switching processes, reflected by the N2 and P3 ERP components,
      are not modulated by the norepinephrine system. Rather, this system modulates
      preparatory processes in the fore period of stimuli signaling possible switches
      of response sets. The source localization results show that this is achieved by
      modulating neural processes in the temporo-parietal junction (BA40). Importantly,
      these phasic modulatory effects of the norepinephrine system were only evident
      when working memory processes had to be used to guide the selection of the
      appropriate responses for task switching.

PMID- 29026993
TI  - Task intentions and their implementation into actions: cognitive control from
      adolescence to middle adulthood.
AB  - Cognitive control processes involved in human multitasking arise, mature, and
      decline across age. This study investigated how age modulates cognitive control
      at two different levels: the level of task intentions and the level of the
      implementation of intentions into the corresponding actions. We were particularly
      interested in specifying maturation of voluntary task choice (intentions) and
      task-switching execution (their implementations) between adolescence and middle
      adulthood. Seventy-four participants were assigned to one of the four age groups
      (adolescents, 12-17 years; emerging adults, 18-22 years; young adults, 23-27
      years; middle-aged adults, 28-56 years). Participants chose between two simple
      cognitive tasks at the beginning of each trial before pressing a spacebar to
      indicate that the task choice was made. Next, a stimulus was presented in one of
      the three adjacent boxes, with participants identifying either the location or
      the shape of the stimulus, depending on their task choice. This voluntary task
      switching paradigm allowed us to investigate the intentional component (task
      choice) separately from its implementation (task execution). Although all
      participants showed a tendency to repeat tasks more often than switching between
      them, this repetition bias was significantly stronger in adolescents than in any
      adult group. Furthermore, participants generally responded slower after task
      switches than after task repetitions. This switch cost was similar across tasks
      in the two younger groups but larger for the shape than the location task in the
      two older groups. Together, our results demonstrate that both task intentions and
      their implementation into actions differ across age in quite specific ways.

PMID- 29026997
TI  - A systematic review of integrative clinical trials for supportive care in
      pediatric oncology: a report from the International Society of Pediatric
      Oncology, T&CM collaborative.
AB  - PURPOSE: Traditional and complementary medicine (T&CM) use in children with
      cancer is well established among high-income, upper middle-income, low-middle
      income, and low-income countries (HIC, UMIC, LMIC, LIC, respectively). In HIC, a
      developing body of evidence exists for several T&CM therapies; however, evidence
      in other income settings is less well described despite a significantly higher
      use when compared to reports from HIC. The aim of this systematic review was to
      evaluate the evidence for T&CM for a variety of supportive care indications among
      children with cancer. METHODS: We performed a systematic review following the
      PRISMA guidelines of randomized, controlled clinical trials from inception
      through September 2016. Our eligibility criteria were limited to T&CM studies
      performed in children and adolescents undergoing treatment for a pediatric
      malignancy. RESULTS: Of 6342 studies identified, 44 met inclusion criteria. Two
      clinical trials reported on acupuncture, 1 reported on aromatherapy, 9 evaluated
      massage therapy, and 32 reported on dietary supplements. Twenty-two studies were
      performed in HIC, 15 in UMIC, and 7 in LMIC. T&CM therapies were most commonly
      investigated for the prevention or management of mucositis, weight loss, and
      febrile neutropenia. Encouraging results were reported for select interventions;
      however, the majority of studies were classified as poor to fair quality.
      CONCLUSION: Our search revealed numerous clinical studies investigating the use
      of T&CM for supportive care purposes in pediatric oncology in HIC, UMIC, and
      LMIC. Although limited, these results could inform supportive care resource
      allocation and indicate where T&CM may serve to fill gaps where access to care
      may be limited.

PMID- 29026995
TI  - Cross-species prophylactic efficacy of Sm-p80-based vaccine and intracellular
      localization of Sm-p80/Sm-p80 ortholog proteins during development in Schistosoma
      mansoni, Schistosoma japonicum, and Schistosoma haematobium.
AB  - Schistosomiasis remains a major global health problem. Despite large-scale
      schistosomiasis control efforts, clear limitations such as possible emergence of
      drug resistance and reinfection rates highlight the need for an effective
      schistosomiasis vaccine. Schistosoma mansoni large subunit of calpain (Sm-p80)
      based vaccine formulations have shown remarkable efficacy in protecting against
      S. mansoni challenge infections in mice and baboons. In this study, we evaluated
      the cross-species protective efficacy of Sm-p80 vaccine against S. japonicum and
      S. haematobium challenge infections in rodent models. We also elucidated the
      expression of Sm-p80 and Sm-p80 ortholog proteins in different developmental
      stages of S. mansoni, S. haematobium, and S. japonicum. Immunization with Sm-p80
      vaccine reduced worm burden by 46.75% against S. japonicum challenge infection in
      mice. DNA prime/protein boost (1 + 1 dose administered on a single day) resulted
      in 26.95% reduction in worm burden in S. haematobium-hamster infection/challenge
      model. A balanced Th1 (IFN-gamma, TNF-alpha, IL-2, and IL-12) and Th2 (IL-4,
      IgG1) type of responses were observed following vaccination in both S. japonicum
      and S. haematobium challenge trials and these are associated with the
      prophylactic efficacy of Sm-p80 vaccine. Immunohistochemistry demonstrated that
      Sm-p80/Sm-p80 ortholog proteins are expressed in different life cycle stages of
      the three major human species of schistosomes studied. The data presented in this
      study reinforce the potential of Sm-p80-based vaccine for both hepatic/intestinal
      and urogenital schistosomiasis occurring in different geographical areas of the
      world. Differential expression of Sm-p80/Sm-p80 protein orthologs in different
      life cycle makes this vaccine potentially useful in targeting different levels of
      infection, disease, and transmission.

PMID- 29026996
TI  - Does personality influence learning? A case study in an invasive lizard.
AB  - Learning is a change in state resulting from new experiences enabling behavioural
      responses to be adjusted in alignment with external cues. Individuals differ in
      the speed and accuracy at which they learn. Personality has been postulated as
      being a major influence on learning ability in terms of attention and encounter
      rates of environmental cues. This link forms the basis of the cognitive style
      hypothesis (CSH), predicting that an individual's cognitive style will occur
      along a fast-slow behavioural gradient. Fast types are characterised as being
      active, neophilic, and bold individuals who sample their environment rapidly, yet
      superficially, enabling learning to occur at a higher speed, but at the cost of
      accuracy. Slow types have the opposite suite of personality traits resulting in
      them being more accurate flexible learners. Greater level of learning flexibility
      is thought to help promote invasions success. Here, we test the predictions of
      the CSH in an invasive lizard (Lampropholis delicata) to determine if personality
      dictates learning performance in a two-phase associative task. Results indicated
      that the delicate skink was capable of learning an associative task but only
      provided partial support for the CSH. Personality was found to influence learning
      accuracy, however, the direction of that relationship was opposite to that
      predicted. Instead, fast lizards made fewer mistakes when learning to associate a
      colour to a goal. These findings highlight the need to further investigate the
      CSH across taxa and consider its potential as an underlying mechanism of the
      invasion process.

PMID- 29026998
TI  - Acetolactate synthase (AlsS) in Bacillus licheniformis WX-02: enzymatic
      properties and efficient functions for acetoin/butanediol and L-valine
      biosynthesis.
AB  - Acetolactate synthase catalyzes two molecules of pyruvates to form alpha
      acetolactate, which is further converted to acetoin and 2,3-butanediol. In this
      study, by heterologous expression in Escherichia coli, the enzymatic properties
      of acetolactate synthase (AlsS) from Bacillus licheniformis WX-02 were
      characterized. Its K m and k cat for pyruvate were 3.96 mM and 514/s,
      respectively. It has the optimal activity at pH 6.5, 37  degrees C and was
      feedback inhibited by L-valine, L-leucine and L-isoleucine. Furthermore, the alsS
      deficient strain could not produce acetoin, 2,3-butanediol, and L-valine, while
      the complementary strain was able to restore these capacities. The alsS
      overexpressing strain produced higher amounts of acetoin/2,3-butanediol (57.06
      g/L) and L-valine (2.68 mM), which were 10.90 and 92.80% higher than those of the
      control strain, respectively. This is the first report regarding the in-depth
      understanding of AlsS enzymatic properties and its functions in B. licheniformis,
      and overexpression of AlsS can effectively improve acetoin/2,3-butanediol and L
      valine production in B. licheniformis. We envision that this AlsS can also be
      applied in the improvement of acetoin/2,3-butanediol and L-valine production in
      other microbes.

PMID- 29026999
TI  - Identification of a novel vitivirus from grapevines in New Zealand.
AB  - We report a sequence of a novel vitivirus from Vitis vinifera obtained using two
      high-throughput sequencing (HTS) strategies on RNA. The initial discovery from
      small-RNA sequencing was confirmed by HTS of the total RNA and Sanger sequencing.
      The new virus has a genome structure similar to the one reported for other
      vitiviruses, with five open reading frames (ORFs) coding for the conserved
      domains described for members of that genus. Phylogenetic analysis of the
      complete genome sequence confirmed its affiliation to the genus Vitivirus, with
      the closest described viruses being grapevine virus E (GVE) and Agave tequilana
      leaf virus (ATLV). However, the virus we report is distinct and shares only 51%
      amino acid sequence identity with GVE in the replicase polyprotein and 66.8%
      amino acid sequence identity with ATLV in the coat protein. This is well below
      the threshold determined by the ICTV for species demarcation, and we propose that
      this virus represents a new species. It is provisionally named "grapevine virus
      G".

PMID- 29027000
TI  - Occupational exposure to perfluoroalkyl substances and serum levels of
      perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in an aging
      population from upstate New York: a retrospective cohort study.
AB  - PURPOSE: Perfluoroalkyl substances (PFASs) are environmentally persistent
      amphiphilic compounds. Exposure to two PFASs, perfluorooctanesulfonic acid (PFOS)
      and perfluorooctanoic acid (PFOA) is linked to specific occupations and
      industries. This study examines the contribution of past occupational PFAS
      exposure to serum PFOS and PFOA levels among 154 older adults in New York State.
      METHODS: Serum PFOS and PFOA levels were compared to data from the National
      Health and Nutrition Examination Survey (NHANES). Potential occupational exposure
      to any PFAS was determined from work histories, reviewed by an industrial
      hygienist, and assessed in relation to current serum PFOS and PFOA levels using
      exposure probability, duration and cumulative exposure. RESULTS: We observed 25%
      higher serum PFOS and 80% higher PFOA levels in study participants compared to
      NHANES. No participants reported PFAS chemical manufacturing work, but n = 68
      reported work in occupations and industries known to use PFASs. We found that
      participants with high cumulative workplace exposure had 34% higher serum PFOS
      levels compared to participants without occupational exposure, adjusted for age,
      sex and income. Serum PFOS levels were 26% higher for participants with longer
      occupational exposure durations. The probability of occupational PFAS exposure
      metric was not associated with serum PFOS. Serum PFOA was not associated with any
      measure of occupational exposure. CONCLUSION: Occupational exposure may
      contribute to total PFOS body burden in this study population, even among workers
      not directly involved in manufacturing PFASs. PFAS exposure assessments should
      evaluate the workplace as a potential source, even when workplace exposures are
      assumed to be low or moderate.

PMID- 29027001
TI  - Cancer incidence in urban, rural, and densely populated districts close to core
      cities in Bavaria, Germany.
AB  - OBJECTIVE: An ecologic study on the level of districts was performed to evaluate
      the possible association between district type and risk of cancer in Bavaria,
      Southern Germany. METHODS: Cancer incidence data for the years 2003-2012 were
      obtained from the population-based cancer registry Bavaria according to sex and
      cancer site. Data on district type, socio-economic area deprivation, particulate
      matter exposure, tobacco consumption, and alcohol consumption were obtained from
      publicly available sources. The possible association between district type and
      cancer risk adjusted for age, socio-economic area deprivation, particulate matter
      exposure, tobacco consumption, and alcohol consumption was evaluated using
      multivariable multi-level negative binomial regression. RESULTS: We found a
      significantly reduced cancer risk in densely populated districts close to core
      cities and/or rural districts compared to core cities with respect to the cancer
      sites mouth and pharynx (women only), liver (both sexes), larynx (both sexes),
      lung (both sexes), melanoma of the skin (both sexes), mesothelioma (men only),
      connective and soft tissue (both sexes), corpus uteri, other urinary tract (men
      only), urinary bladder (both sexes), and non-Hodgkin lymphoma (both sexes).
      CONCLUSION: Our findings require further monitoring. Since the apparently
      increased cancer risk in core cities may be related to lifestyle factors,
      preventive measures against lifestyle-related cancer could be specifically
      targeted at populations in deprived core cities.

PMID- 29027003
TI  - Explaining long-term inter-individual growth variation in plant populations:
      persistence of abiotic factors matters.
AB  - An unanswered question in ecology is whether the environmental factors driving
      short-term performance also determine the often observed long-term performance
      differences among individuals. Here, we analyze the extent to which temporal
      persistence of spatial heterogeneity in environmental factors can contribute to
      long-term inter-individual variation in stem length growth. For a natural
      population of a long-lived understorey palm, we first quantified the effect of
      several environmental factors on stem length growth and survival. We then
      performed individual-based simulations of growth trajectories, in which we
      varied, for two environmental factors: (1) the strength of the effect on stem
      length growth and (2) the temporal persistence. Short-term variation in stem
      length growth was strongly driven by light availability. Auto-correlation in
      light availability and soil pH increased simulated variation in stem length
      growth among 20-year-old palms to levels similar to the observed variation.
      Analyses in which we varied both the strength of the effect on stem length growth
      and the temporal persistence of the environmental factors revealed that a large
      fraction of observed long-term growth differences can be explained, as long as
      one of these effects is strong. This implies that environmental factors that are
      relatively unimportant for short-term performance can still drive long-term
      performance differences when the environmental variation is sufficiently
      persistent over time.

PMID- 29027002
TI  - Camel molar tooth enamel response to gamma rays using EPR spectroscopy.
AB  - Tooth enamel samples from molar teeth of camel were prepared using a combined
      procedure of mechanical and chemical tooth treatment. Based on electron
      paramagnetic resonance (EPR) spectroscopy, the dose response of tooth enamel
      samples was examined and compared to that of human enamel. The EPR dose response
      of the tooth enamel samples was obtained through irradiation to gamma doses from
      1 Gy up to 100 kGy. It was found that the radiation-induced EPR signal increased
      linearly with gamma dose for all studied tooth enamel samples, up to about 15
      kGy. At higher doses, the dose response curve leveled off. The results revealed
      that the location of the native signal of camel tooth enamel was similar to that
      of enamel from human molars at 2.00644, but different from that of enamel from
      cows and goats. In addition, the peak-to-peak width (DeltaH pp) for human and
      camel molar teeth was similar. It was also found that the response of camel
      enamel to gamma radiation was 36% lower than that of human enamel. In conclusion,
      the results indicate the suitability of camel teeth for retrospective gamma
      dosimetry.

PMID- 29027004
TI  - Blood lymphocyte subsets identify optimal responders to IFN-beta in MS.
AB  - Response to interferon-beta (IFN-beta) treatment is heterogeneous in multiple
      sclerosis (MS). We aimed to search for biomarkers predicting no evidence of
      disease activity (NEDA) status upon IFN-beta treatment in MS. 119 patients with
      relapsing-remitting MS (RRMS) initiating IFN-beta treatment were included in the
      study, and followed prospectively for 2 years. Neutralizing antibodies (NAb) were
      explored in serum samples obtained after 6 and 12 months of IFN-beta treatment.
      Soluble cytokines and blood lymphocytes were studied in basal samples by ELISA
      and flow cytometry, respectively. 9% of patients developed NAb. These antibodies
      were more frequent in patients receiving IFN-beta 1b than in those treated
      subcutaneous (p = 0.008) or intramuscular (p < 0.0001) IFN-beta 1a. No patient
      showing NAb remained NEDA during follow-up. Basal immunological variables are
      also associated with patient response. Percentages below 3% of CD19 + CD5 + cells
      (AUC 0.74, CI 0.63-0.84; OR 10.68, CI 3.55-32.15, p < 0.0001; Likelihood ratio
      4.28) or above 2.6% of CD8 + perforin + T cells (AUC 0.79, CI 0.63-0.96; OR 6.11,
      CI 2.0-18.6, p = 0.0009; Likelihood ratio 5.47) increased the probability of
      achieving NEDA status during treatment. Basal blood immune cell subsets
      contribute to identify MS patients with a high probability of showing an optimal
      response to IFN-beta.

PMID- 29027005
TI  - Utility of the revised Edmonton Symptom Assessment System (ESAS-r) and the
      Patient-Reported Functional Status (PRFS) in lung cancer patients.
AB  - BACKGROUND: Symptom palliation is an important objective of treatment in
      advanced/metastatic lung cancer (LC). Significant psychological, minor physical
      symptoms and several social/emotional issues often go unnoticed. This prospective
      study aimed to evaluate utility of patients' perspectives [self-reported symptom
      assessment by revised Edmonton Symptom Assessment System (ESAS-r) and self
      reported functional status by Patient-Reported Functional Status (PRFS)] amongst
      LC patients undergoing chemotherapy. METHODS: Consecutive newly diagnosed
      treatment-naive LC patients attending a tertiary referral center in North India
      from January 2014 to March 2015 were included. All patients received standard
      histology-guided platinum-doublet chemotherapy. ESAS-r and PRFS questionnaires
      were administered under guidance, once at the time of initial
      assessment/diagnosis, repeated at start of chemotherapy, before C4, and after
      completion of chemotherapy (end of chemotherapy (EOCTx)). Functional Assessment
      of Cancer Therapy-Lung (FACT-L) questionnaire was also administered. Baseline and
      post-treatment scores were compared. RESULTS: Majority of 133 patients enrolled
      were males (86.5%,n = 115), were current/ex-smokers (81.2%, n = 108), had
      advanced stage [IIIB = 30.1% (n = 40), IV = 52.6% (n = 70)], and were of non
      small-cell type (NSCLC;84.2%,n = 112). On baseline ESAS-r, the highest mean
      symptom scores were observed for tiredness followed by anorexia. Mean ESAS-r
      scores before C4 as well as at EOCTX were significantly better than baseline ESAS
      r scores in all its components except nausea. Similarly, PRFS before C4 and EOCTx
      was significantly improved compared to baseline. However, Karnofsky Performance
      Scale (KPS) and Eastern Cooperative Oncology Group Performance Status assessed at
      baseline did not show significant improvement at treatment completion. FACT-L
      score at EOCTx showed significant improvement from baseline in physical and
      functional well-being domains but not for social/family and emotional well-being
      domains. CONCLUSION: This study validated utility of ESAS-r and PRFS in Indian LC
      patients. These instruments should be used in routine clinical practice besides
      physicians' assessment of PS (KPS/ECOG).

PMID- 29027007
TI  - Lumbosacral stress and age may contribute to increased pelvic incidence: an
      analysis of 1625 adults.
AB  - PURPOSE: While there is a consensus that pelvic incidence (PI) remains constant
      after skeletal maturity, recent reports argue that PI increases after 60 years.
      This study aims to investigate whether PI increases with age and to determine
      potential associated factors. METHODS: 1510 patients with various spinal
      degenerative and deformity pathologies were enrolled, along with an additional
      115 asymptomatic volunteers. Subjects were divided into six age subgroups with 10
      year intervals. RESULTS: PI averaged 54.1 degrees  in all patients. PI was
      significantly higher in the 45-54-year age group than 35-44-year age group (55.8
      degrees  vs. 49.7 degrees ). There were significant PI differences between
      genders after age 45. Linear regression revealed age, gender and malalignment as
      associated factors for increased PI with R 2 of 0.22 (p < 0.001). CONCLUSIONS: PI
      is higher in female patients and in older patients, especially those over 45
      years old. Spinal malalignment also may have a role in increased PI due to
      increased L5-S1 bending moment.

PMID- 29027006
TI  - Comparative outcomes of combined corticosteroid with low volume compared to high
      volume of local anesthetic in subacromial injection for impingement syndrome:
      systematic review and meta-analysis of RCTs.
AB  - Subacromial impingement syndrome (SIS) is one of the most frequent pathologies of
      the shoulder, which may cause serious restriction of daily activities and
      lifestyle changes. Corticosteroid injection (CI) into the subacromial space is a
      palliative treatment option. Currently, there have been no studies that compare
      between the different volumes of CI injection. We have conducted a systematic
      review and meta-analysis to answer our specific study questions: Are high volume
      (< 5 ml) better than low volume (>= 5 ml) of CI injection with respect to pain
      reduction? This systematic review was conducted according to the preferred
      reporting items for systematic reviews and meta-analyses guidelines. Relevant
      studies were identified from Medline and Scopus from inception to May 11, 2017
      that reported American shoulder and elbow surgeons (ASES) function score, pain
      visual analog score (VAS), and postoperative complications of either group.
      Fifteen studies were included for the analysis of high volume (more than or equal
      5 ml), and 5 studies were included for analysis of low volume (less than 5 ml).
      Overall, there were 1101 patients (732 in the high-volume group and 369 in the
      low-volume group). A pooling of mean VAS and ASES function score was (N = 557)
      2.02 (95% CI 1.52, 2.53), (N = 190) 82.59 (95% CI 76.92, 88.27) in high-volume
      group and (N = 179) 2.60 (95% CI 1.94, 3.26), (N = 95) 84.65 (95% CI 81.64,
      86.82) in low-volume group, respectively. The unstandardized mean difference of
      ASES and VAS of high volume was - 0.58 (95% confidence interval (CI): - 1.38,
      0.22) and - 2.06 (95% CI - 8.35, 4.23) scores lower than low-volume CI in SIS
      patients, but without statistical significance. A total of 11 studies in the high
      volume group and 4 studies in the low-volume group reported adverse effects. The
      total complication rate per patient was 6.2% (2.3, 10.1%) in the high-volume
      group and 11.7% (0.3, 12%) in the low-volume group (p = 0.091). No significant
      differences were noted for complications. In subacromial impingement syndrome,
      the corticosteroid injection had acceptable pain and functional outcomes. Higher
      volume had a lower ASES, VAS, and risk of having complication when compared to
      lower volume. However, there are no statistically significant differences between
      groups. Larger, randomized noninferiority or equivalent trial studies are needed
      to confirm these findings as the current literature is still insufficient. Level
      of evidence I.

PMID- 29027008
TI  - Lateral epicondylitis: Associations of MR imaging and clinical assessments with
      treatment options in patients receiving conservative and arthroscopic
      managements.
AB  - OBJECTIVES: We assessed the implications of MR imaging with clinical history in
      lateral epicondylitis management by evaluating imaging and clinical features in
      patients with lateral epicondylitis treated conservatively or operatively.
      METHODS: Sixty patients with lateral epicondylitis treated conservatively (n =
      38) or operatively (n = 22) from 2011-2015 were included. MR imaging findings of
      common extensor tendon (CET), lateral collateral ligament (LCL) complex, muscle
      oedema, ulnar nerve and elbow joint were reviewed. Clinical data recorded were
      frequency, duration and intensity of pain, history of trauma and injection
      therapy, range of motion. RESULTS: MRI-assessed CET and LCL complex
      abnormalities, muscle oedema, radiocapitellar joint widening, joint
      effusion/synovitis, pain frequency and intensity differed significantly between
      the two groups (p < .05) with increased severity in operative group. Persistent
      pain (OR 12.2, p < .01), CET abnormality on longitudinal plane (OR 7.5, p = .03
      for grade 2; OR 22.4, p < .01 for grade 3) and muscle oedema (OR 6.7, p = .03)
      were major factors associated with operative treatment. Area under the ROC curve
      of predicted probabilities for combination of these factors was 0.83. CONCLUSION:
      MR imaging, combined with clinical assessment, could facilitate appropriate
      management planning for patients with lateral epicondylitis. KEY POINTS: * MRI
      can reflect different disease severity between patients treated
      conservatively/operatively. * CET abnormality, muscle oedema were major MRI
      findings with operative treatment. * Patients in operative group were more likely
      to experience persistent pain. * MRI plus clinical symptoms could facilitate
      appropriate management for lateral epicondylitis.

PMID- 29027009
TI  - Lipid-lowering agent-triggered dermatomyositis and polymyositis: a case series
      and literature review.
AB  - Lipid-lowering agent-triggered dermatomyositis (DM) or polymyositis (PM) is a
      rare event. Therefore, the aim of the present study was to describe a series of
      such cases. A retrospective cohort study of 5 DM and 4 PM cases triggered by
      prior exposure to lipid-lowering agents between 2001 and 2017 was carried out.
      All patients, except for two cases, had muscle biopsy compatible with
      inflammatory myopathy and no serum autoantibodies positive for anti-SRP or anti
      HMGCoAR. Median age of the patients at time of diagnosis was 68 years. Seven
      patients had previously taken simvastatin 20 mg/day (exposure period from 2 days
      to 4 years) and two bezafibrate 100 mg/day (3-4 months). Median time from symptom
      onset to disease diagnosis was 6 months. All patients with DM had a heliotrope
      and/or Gottron's papules. All patients had symmetrical, predominantly proximal
      muscle weakness of limbs, with median serum creatine phosphokinase of 3087U/L
      (interquartile 25-75% range 1293-13,937 U/L). All patients received
      glucocorticoid and immunosuppressants. Complete reversal of clinical symptoms and
      normalization of serum creatine phosphokinase level occurred within a median of
      12 months after starting the treatment. There was disease relapse in three cases,
      and one case of death was unrelated to the disease (pulmonary infectious
      complications resulting from lymphoma). In contrast to cases described in the
      literature, the patients in the present study had a relatively more aggressive
      course, requiring glucocorticoids and immunosuppressants, in addition to a
      tendency for a longer period to achieve disease remission.

PMID- 29027010
TI  - Oxidized regenerated cellulose induces pleural thickening in patients with
      pneumothorax: possible involvement of the mesothelial-mesenchymal transition.
AB  - PURPOSE: The pleural covering technique, i.e., wrapping a part of or the entire
      surface of the lung with oxidized regenerative cellulose (ORC), reinforces
      visceral pleura through pleural thickening for patients with pneumothorax and
      cystic lung diseases. However, it remains undetermined how ORC induces pleural
      thickening. METHODS: A histopathological examination was performed for lung
      specimens from patients who had recurrent pneumothoraces after pleural covering
      and re-operation (n = 5). To evaluate the influence of ORC on the pleura in
      vitro, we used MeT-5A cells (a human pleural mesothelial cell line). RESULTS:
      Pleural thickening was confirmed in all lung specimens examined. Three months
      after covering, the thickened pleura showed inflammatory cell infiltration,
      proliferation of myofibroblasts, and expression of fibronectin and TGF-beta.
      However, after 1 year, those findings virtually disappeared, and the thickened
      pleura was composed mainly of abundant collagen. When MeT-5A cells were cultured
      in ORC-immersed medium, their morphology changed from a cobblestone to spindle
      shaped appearance. The expression of E-cadherin decreased, whereas that of N
      cadherin, alpha-smooth muscle actin, and fibronectin increased, suggesting
      mesothelial-mesenchymal transition (Meso-MT). CONCLUSIONS: Our results suggest
      that Meso-MT may be involved as a mechanism of pleural thickening induced by
      pleural covering with ORC.

PMID- 29027012
TI  - Causes of death, survival and risk factors of mortality in Thai patients with
      early systemic sclerosis: inception cohort study.
AB  - Inception cohort study regarding the causes of death and risk factors for
      mortality in patients with early systemic sclerosis (SSc), especially diffuse SSc
      (dcSSc) has not been well elucidated. Therefore, the aim of our study was to
      determine the causes of death, survival rates, and risk factors for mortality in
      Thai patients with early SSc of whom the majority belonged to the dcSSc subset.
      We used an inception cohort of early-SSc patients seen between January 2010 and
      August 2014. All patients were evaluated for clinical and laboratory data at the
      study entry and then every 6 months. A total of 115 patients (68 female, 91
      dcSSc) were enrolled. The mean +/- SD age at onset, duration of disease, and
      duration of follow-up were 52.5 +/- 8.5 years, 12.3 +/- 9.2 months, and 27.5 +/-
      16.4 months, respectively. During the follow-up, 11(9.6%) SSc patients died. The
      mortality rate was 4.17 per 100 person-years (95% CI 2.31, 7.53). The leading
      cause of SSc-related death was dilated cardiomyopathy (27.2%). Infection was the
      most common cause of non-SSc-related death (18.2%). Survival rates at 1, 2, 3,
      and 4 years after the study entry were 93, 91, 88, and 88%, respectively. In the
      multivariate Cox regression analysis, ESR >= 40 mm/h [HR 8.65 (95% CI
      1.66,45.17)], hemoglobin < 10 mg/dL [HR 4.57 (95% CI 1.14,18.34)], and mRSS [HR
      1.09 (95% CI 1.03,1.15)] were independent risk factors for mortality. Our data
      suggest that dilated cardiomyopathy was the most common SSc-related cause of
      death in Thai patients with early SSc, of whom majority was dcSSc subset.
      Elevated ESR, anemia, and increased mRSS predicted poor outcome.

PMID- 29027013
TI  - A systematic review of maternal antidepressant use in pregnancy and short- and
      long-term offspring's outcomes.
AB  - The relative safety of antidepressants during pregnancy has received substantial
      attention, but most syntheses fail to account for mental illness effects. We
      aimed to evaluate the literature comparing low birth weight (LBW) and
      neurodevelopmental and neurobehavioural outcomes for children whose mothers took
      antidepressants in pregnancy compared to those whose mothers had common mental
      disorders, or symptoms, but who did not take antidepressants during pregnancy. A
      systematic review was conducted searching PubMed, MEDLINE, PsycINFO and Embase in
      January 2015. A modified version of the Newcastle Ottawa Scale was used to assess
      study quality. Eleven cohort studies were included: four reporting a LBW outcome
      (all with higher risk of bias) and seven reporting a neurodevelopmental outcome
      (five with higher risk of bias). We found only limited evidence of gestational
      age-adjusted LBW in exposed children in two studies which had a higher risk of
      bias and did not control for depressive symptom severity. Only five (7.5%)
      neurodevelopmental outcomes and one (12.5%) neurobehavioural outcome showed
      evidence of a statistically significant effect, three out of four were from
      studies with a higher risk of bias. There is little robust evidence indicating a
      detrimental effect of antidepressant use during pregnancy on LBW and
      neurodevelopmental and neurobehavioural outcomes. More rigorous study designs are
      needed.

PMID- 29027014
TI  - Proton-beam therapy or photon-beam radiosurgery for WHO grade I meningiomas?

PMID- 29027015
TI  - Cerebral microdialysis in TBI-limitations and possibilities.

PMID- 29027016
TI  - Impact of flow shear stress on morphology of osteoblast-like IDG-SW3 cells.
AB  - This study constructed an in situ cell culture, real-time observation system
      based originally on a microfluidic channel, and reported the morphological
      changes of late osteoblast-like IDG-SW3 cells in response to flow shear stress
      (FSS). The effects of high (1.2 Pa) and low (0.3 Pa) magnitudes of unidirectional
      FSS and three concentrations of extracellular Type I collagen (0.1, 0.5, and 1
      mg/mL) coating on cell morphology were investigated. IDG-SW3 cells were cultured
      in polydimethylsiloxane microfluidic channels. Cell images were recorded real
      time under microscope at intervals of 1 min. Cell morphology was characterized by
      five parameters: cellular area, cell elongation index, cellular alignment,
      cellular process length, and number of cellular process per cell.
      Immunofluorescence assay was used to detect stress fiber distribution and
      vinculin expression. The results showed that 1.2 Pa, but not 0.3 Pa of FSS
      induced a significant morphological change in late osteoblast-like IDG-SW3 cells,
      which may be caused by the alteration of cellular adhesion with matrix in
      response to FSS. Moreover, the amount of collagen matrix, alignment of fiber
      stress and expression of vinculin were closely correlated with the morphological
      changes of IDG-SW3 cells. This study suggests that osteoblasts are very
      responsive to the magnitudes of FSS, and extracellular collagen matrix and focal
      adhesion are directly involved in the morphological changes adaptive to FSS.

PMID- 29027017
TI  - Palladium bionanoparticles production from acidic Pd(II) solutions and spent
      catalyst leachate using acidophilic Fe(III)-reducing bacteria.
AB  - The acidophilic, Fe(III)-reducing heterotrophic bacteria Acidocella aromatica
      PFBCT and Acidiphilium cryptum SJH were utilized to produce palladium (Pd)
      bionanoparticles via a simple 1-step microbiological reaction. Monosaccharide (or
      intracellular NADH)-dependent reactions lead to visualization of intra/extra
      cellular enzymatic Pd(0) nucleation. Formic acid-dependent reactions proceeded
      via the first slow Pd(0) nucleation phase and the following autocatalytic Pd(II)
      reduction phase regardless of the presence or viability of the cells. However,
      use of active cells (with full enzymatic and membrane protein activities) at low
      formic acid concentration (5 mM) was critical to allow sufficient time for Pd(II)
      biosorption and the following enzymatic Pd(0) nucleation, which consequently
      enabled production of fine, dense and well-dispersed Pd(0) bionanoparticles.
      Differences of the resultant Pd(0) nanoparticles in size, density and
      localization between the two bacteria under each condition tested suggested
      different activity and location of enzymes and membrane "Pd(II) trafficking"
      proteins responsible for Pd(0) nucleation. Despite the inhibitory effect of
      leaching lixiviant and dissolved metal ions, Pd(0) bionanoparticles were
      effectively formed by active Ac. aromatica cells from both acidic synthetic
      Pd(II) solutions and from the actual spent catalyst leachates at equivalent 18-19
      nm median size with comparable catalytic activity.

PMID- 29027018
TI  - Accelerated growth of hemangioblastoma in pregnancy: the role of proangiogenic
      factors and upregulation of hypoxia-inducible factor (HIF) in a non-oxygen
      dependent pathway.
AB  - Hemangioblastomas (HBs) are benign, highly vascular tumors, often characterized
      by loss of function of the von Hippel-Lindau (vHL) gene. They are the most common
      central nervous system tumor observed in vHL syndrome. Loss of function of the
      vHL gene creates a "pseudo-hypoxic" state, causing overactivation of hypoxia
      inducible factor (HIF) and vascular endothelial growth factor (VEGF)-related
      pathways. In some cases, HBs can rapidly increase in size during pregnancy to
      then present acutely, which most frequently occurs after the 20th gestational
      week. These changes in size usually occur from enlargement of the cystic
      component of the HB. Due to their preferred location in the posterior fossa near
      critical structures as well as along the spinal cord, such cases can present with
      severe neurological deficits, requiring urgent surgical intervention in a
      multidisciplinary setting. However, the reasons for this acute flare-up during
      pregnancy remain poorly understood, as are the reasons why this occurs in only a
      subset of tumors. Unveiling the etiology for this clinical scenario can affect
      the treatment of HBs, as it will contribute to the understanding of the
      pathophysiology of such a transformation from a quiescent lesion to a symptomatic
      one, not only in the setting of pregnancy. Identifying the correct triggers and
      the conditions initiating and mediating this switch will enable us to develop
      preventive medications which should allow us to keep the tumor in its quiescent
      phase. In this pathophysiological review, we investigate the association between
      HB growth and pregnancy based on an analysis > 40 such published cases. We
      suggest that the proangiogenic state of pregnancy is the leading etiology for
      this striking association, and to support the argument, we discuss its potential
      impact on HIF overexpression in a non-hypoxic manner through activation of the
      PI3K/Akt/mTOR pathway by proangiogenic factors. Specifically, we discuss the
      involvement of placental growth factor (PlGF) and its receptor vascular
      endothelial growth factor receptor 1 (VEGFR-1) in various pathologic processes
      that can lead to the formation and growth of peritumoral edema and cysts, which
      are the primary causes for the development of any symptoms in HB. Both PlGF and
      VEGFR-1 are expressed at increased levels during pregnancy, and both have been
      reported as part of various pathological processes, including angiogenesis and
      tumorigenesis. The unique feature that both do essentially not show any
      significant negative impact on regular physiological processes makes them
      attractive therapeutic targets since very little side effects are expected.
      Further research into the effects of anti-PlGF or anti-VEGFR-1 therapy in HB is
      therefore recommended.

PMID- 29027011
TI  - Let's make microglia great again in neurodegenerative disorders.
AB  - All of the common neurodegenerative disorders-Alzheimer's disease, Parkinson's
      disease, amyotrophic lateral sclerosis and prion diseases-are characterized by
      accumulation of misfolded proteins that trigger activation of microglia; brain
      resident mononuclear phagocytes. This chronic form of neuroinflammation is
      earmarked by increased release of myriad cytokines and chemokines in patient
      brains and biofluids. Microglial phagocytosis is compromised early in the disease
      process, obfuscating clearance of abnormal proteins. This review identifies
      immune pathologies shared by the major neurodegenerative disorders. The
      overarching concept is that aberrant innate immune pathways can be targeted for
      return to homeostasis in hopes of coaxing microglia into clearing neurotoxic
      misfolded proteins.

PMID- 29027019
TI  - Explorative results from multistep screening for potential genetic risk loci of
      Alzheimer's disease in the longitudinal VITA study cohort.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder that preferentially
      affects individuals of advanced age. Heritability estimates for AD range between
      60 and 80%, but only few genetic risk factors have been identified so far. In the
      present explorative study, we aimed at characterizing the genetic contribution to
      late-onset AD in participants of the Vienna Transdanube Aging (VITA) longitudinal
      birth cohort study in a two-step approach. First, we performed a genome-wide
      screen of pooled DNA samples (n = 588) to identify allele frequency differences
      between AD patients and non-AD individuals using life-time diagnoses made at the
      age of 80 (t = 60 months). This analysis suggested a high proportion of brain
      expressed genes required for cell adhesion, cell signaling and cell
      morphogenesis, and also scored in known AD risk genes. In a second step, we
      confirmed associations using individual genotypes of top-ranked markers examining
      AD diagnoses as well as the dimensional scores: FULD and MMSE determined up to
      the age of 82.5 (t = 90 months). Taken together, our study proposes genes ANKS1B,
      ENST00000414107, LOC100505811, SLC22A14, QRFPR, ZDHHC8P1, ADAMTS3 and PPFIA1 as
      possible new candidates involved in the etiology of late-onset AD, with further
      research being needed to clarify their exact roles.

PMID- 29027020
TI  - Analysis of Ca2+ response of osteocyte network by three-dimensional time-lapse
      imaging in living bone.
AB  - Osteocytes form a three-dimensional (3D) cellular network within the mineralized
      bone matrix. The cellular network has important roles in mechanosensation and
      mechanotransduction related to bone homeostasis. We visualized the embedded
      osteocyte network in chick calvariae and observed the flow-induced Ca2+ signaling
      in osteocytes using 3D time-lapse imaging. In response to the flow, intracellular
      Ca2+ ([Ca2+]i) significantly increased in developmentally mature osteocytes in
      comparison with young osteocytes in the bone matrix. To investigate the
      differences in response between young and developmentally mature osteocytes in
      detail, we evaluated the expression of osteocyte-related genes using the
      osteocyte-like cell line MLO-Y4, which was 3D-cultured within type I collagen
      gels. We found that the c-Fos, Cx43, Panx3, Col1a1, and OCN mRNA levels
      significantly increased on day 15 in comparison with day 7. These findings
      indicate that developmentally mature osteocytes are more responsive to mechanical
      stress than young osteocytes and have important functions in bone formation and
      remodeling.

PMID- 29027021
TI  - Bortezomib prevents ovariectomy-induced osteoporosis in mice by inhibiting
      osteoclast differentiation.
AB  - Bone homeostasis is achieved through coordinated activities of bone-forming
      osteoblasts and bone-resorbing osteoclasts. When the balance is skewed in favor
      of osteoclasts due to hormonal or inflammatory issues, pathologic bone loss
      occurs leading to conditions such as osteoporosis, rheumatoid arthritis, and
      periodontitis. Bortezomib is the first in-class of proteasome inhibitors used as
      an anti-myeloma agent. In the present study, we show that bortezomib directly
      inhibited the receptor activator of nuclear factor kappaB ligand (RANKL)
      dependent osteoclast differentiation of mouse bone marrow macrophages. Bortezomib
      significantly reduced the induction of osteoclast marker genes and proteins
      including nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). The
      intraperitoneal injection of bortezomib reduced ovariectomy-induced
      osteoclastogenesis and protected the mice from bone loss. These data propose
      novel use of bortezomib as a potential anti-resorptive agent.

PMID- 29027022
TI  - An eFTD-VP framework for efficiently generating patient-specific anatomically
      detailed facial soft tissue FE mesh for craniomaxillofacial surgery simulation.
AB  - Accurate surgical planning and prediction of craniomaxillofacial surgery outcome
      requires simulation of soft tissue changes following osteotomy. This can only be
      achieved by using an anatomically detailed facial soft tissue model. The current
      state-of-the-art of model generation is not appropriate to clinical applications
      due to the time-intensive nature of manual segmentation and volumetric mesh
      generation. The conventional patient-specific finite element (FE) mesh generation
      methods are to deform a template FE mesh to match the shape of a patient based on
      registration. However, these methods commonly produce element distortion.
      Additionally, the mesh density for patients depends on that of the template
      model. It could not be adjusted to conduct mesh density sensitivity analysis. In
      this study, we propose a new framework of patient-specific facial soft tissue FE
      mesh generation. The goal of the developed method is to efficiently generate a
      high-quality patient-specific hexahedral FE mesh with adjustable mesh density
      while preserving the accuracy in anatomical structure correspondence. Our FE mesh
      is generated by eFace template deformation followed by volumetric
      parametrization. First, the patient-specific anatomically detailed facial soft
      tissue model (including skin, mucosa, and muscles) is generated by deforming an
      eFace template model. The adaptation of the eFace template model is achieved by
      using a hybrid landmark-based morphing and dense surface fitting approach
      followed by a thin-plate spline interpolation. Then, high-quality hexahedral mesh
      is constructed by using volumetric parameterization. The user can control the
      resolution of hexahedron mesh to best reflect clinicians' need. Our approach was
      validated using 30 patient models and 4 visible human datasets. The generated
      patient-specific FE mesh showed high surface matching accuracy, element quality,
      and internal structure matching accuracy. They can be directly and effectively
      used for clinical simulation of facial soft tissue change.

PMID- 29027023
TI  - How we do it: repair of large perineal hernia after abdominoperineal resection.
AB  - BACKGROUND: Symptomatic perineal hernia is a rare complication after
      abdominoperineal resection (APR). Management of these hernias is challenging. The
      recurrence rate after surgical repair is high because of the difficulty of
      prosthetic material fixation; there is no consensus regarding the best method of
      repair. METHODS: We introduced a novel combined laparoscopic-perineal dual
      fixation technique in the repair of perineal hernias after APR. This technique
      begins with a perineal approach under laparoscopic vision. After excision of the
      hernia sac, the mesh is introduced and fixed anteriorly to the urogenital
      diaphragm and laterally to the sacrotuberous ligament and the surrounding scar
      tissue. The perineal incision is then closed. Next, the mesh is fixed to the
      sacrum with ProTack(r) and is fixed again to the sacrotuberous ligament via a
      laparoscopic approach. RESULTS: The dual fixation repair method is successful and
      without difficulties, with no recurrence at 13-month follow-up. CONCLUSION: Our
      laparoscopic-perineal dual fixation method is a good alternative method for large
      perineal hernia repair after APR.

PMID- 29027024
TI  - Studies on the constituents of Helleborus purpurascens: analysis and biological
      activity of the aqueous and organic extracts.
AB  - In Southeast Europe, the ethnomedicinal use of Helleborus species has a very long
      tradition. Cardiac steroids (Hellebrin), cysteine-rich proteins (Hellethionins)
      and several steroidal saponins have been identified in these plants. Aim of the
      present work was to investigate the amino acid composition of native extracts
      from the root and rootstock of Helleborus purpurascens. The amino acids have been
      identified by the GC-MS technique on the previously derivatised (Phenomenex Faast
      Kit) extract samples by comparison with the mass spectra and retention-time of
      the standards. A remarkable finding was a relatively intensive peak attributed to
      the non-proteinogenic Pipecolic acid (Pic). A cyclisation of the derivatised
      glutamine was observed during the GC measurement and a mechanistic pathway is
      described. Samples of the extract and of some isolated fractions have also been
      tested on; altogether 12 cancer cell lines aimed to identify further potentially
      cytostatic components which should be less toxic than Hellebrin. The finding of
      one Hellebrin-free fraction (IC50 = 0.007 mg/L) with higher cytotoxicity than
      Hellebrin (IC50 = 0.008 mg/L) is remarkable.

PMID- 29027025
TI  - Spontaneous integration of temporal information: implications for
      representational/computational capacity of animals.
AB  - How do animals adapt their behaviors to changing conditions? This question
      relates to the debate between associative versus representational/computational
      approaches in cognitive science. An influential line of research that has
      significantly shaped the conceptual development of animal learning over decades
      has primarily focused on the role of associative dynamics with little-to-no
      ascription of representational/combinatorial capacities. The common assumption of
      these models is that behavioral adjustments are incremental and they result from
      updating of associations based on actions and their outcomes, without encoding
      the critical information serving as the determinant(s) of such contingencies
      (e.g., time in interval schedules, number in ratio schedules). On the other hand,
      an independent line of research provides evidence for behavioral phenomena that
      cannot be readily accounted for by the conventional associationist approach. In
      this paper, we will review different sets of findings particularly in the area of
      interval timing that suggest the ability of animals to make swift spontaneous
      computations on subjective quantities and incorporate them into their behavior.
      Findings of these studies constitute empirical challenges for the associationist
      approaches to behavioral flexibility. We argue that interval timing is a fertile
      ground for the formulation of critical tests of different theoretical approaches
      to animal behavior.

PMID- 29027026
TI  - Analysis of choroidal thickness in ocular hypertensive patients using enhanced
      depth imaging optical coherence tomography.
AB  - This study aimed to compare choroidal thickness between subjects with ocular
      hypertension (OHT) and normal individuals and explore factors affecting choroidal
      thickness. This study included 60 untreated newly diagnosed OHT eyes and 60
      normal eyes. Choroidal thickness obtained from Cirrus HD-OCT was measured at
      different locations in the macular and peripapillary regions and compared between
      the two groups before and after adjusting for potential confounding variables.
      Regression analysis was performed to figure out factors influencing choroidal
      thickness. The macular choroidal thickness did not vary significantly between OHT
      patients and normal controls regardless of locations (all P > 0.05). The average
      peripapillary choroidal thickness was 167 +/- 53 MUm in OHT eyes and 185 +/- 63
      MUm in the normal eyes; no significant differences were identified (P = 0.107).
      Only one of the locations in the temporal area in the OHT group demonstrated
      significantly thinner peripapillary choroidal thickness as compared to the normal
      group (P = 0.033). Age was the only significant factor affecting choroidal
      thickness on multivariate analysis regardless of locations (all P < 0.001).
      Choroidal thickness of the macular and peripapillary regions in OHT patients is
      not decreased significantly except one location in the temporal area of the optic
      disc when comparing with the normal subjects. Anatomic peripapillary choroidal
      thickness measurements with SD-OCT might be one more tool to track changes in OHT
      patients.

PMID- 29027027
TI  - Decoupling of behavioural and physiological thermal performance curves in
      ectothermic animals: a critical adaptive trait.
AB  - Thermal performance curves (TPCs) represent an increasingly popular tool in
      ecology for anticipating species responses to climate change. TPC theory has been
      developed using species that experience similar temperatures during activity and
      at rest and consequently exhibit thermal ranges for activity that closely
      coincide with their physiological thermal tolerances. Many species, however,
      experience other stressors, such as desiccation, that limit active behaviour at
      temperatures below the maximum values experienced. As a result, activity is
      constrained to a narrow thermal window that is a subset of the range of
      temperatures that can be tolerated physiologically. This results in a decoupling
      of behavioural and physiological TPCs that does not conform to the present
      paradigm. To test the generality of TPC theory, we measured thermal responses for
      behaviour (crawling speed) and physiological tolerance (heart rate) for six rocky
      shore gastropods spanning a thermal/desiccation stress gradient. We hypothesized
      a positive relationship between shore level and the degree of decoupling of
      behavioural and physiological TPCs. This prediction was confirmed, and was
      explained by the extension of the physiological TPC beyond the range of the
      behavioural TPC. Decoupling of behavioural and physiological TPCs is central to
      predicting accurately the fitness dynamics of ectothermic species subject to
      multiple stressors. We believe that this decoupling should be explicitly
      considered as an adaptive trait defining an organism's thermal niche.

PMID- 29027028
TI  - Determination of avidity of IgG against protein antigens from Streptococcus
      pneumoniae: assay development and preliminary application in clinical settings.
AB  - The measurement of antibody levels is a common test for the diagnosis of
      Streptococcus pneumoniae infection in research. However, the quality of antibody
      response, reflected by avidity, has not been adequately evaluated. We aimed to
      evaluate the role of avidity of IgG against eight pneumococcal proteins in
      etiologic diagnosis. Eight pneumococcal proteins (Ply, CbpA, PspA1 and 2, PcpA,
      PhtD, StkP-C, and PcsB-N) were used to develop a multiplex bead-based avidity
      immunoassay. The assay was tested for effects of the chaotropic agent,
      multiplexing, and repeatability. The developed assay was applied to paired
      samples from children with or without pneumococcal disease (n = 38 for each
      group), determined by either serology, polymerase chain reaction (PCR), or blood
      culture. We found a good correlation between singleplex and multiplex assays,
      with r >= 0.94.The assay was reproducible, with mean inter-assay variation <= 9%
      and intra-assay variation < 6%. Children with pneumococcal disease had lower
      median avidity indexes in the acute phase of disease for PspA1 and 2 (p = 0.042),
      PcpA (p = 0.002), PhtD (p = 0.014), and StkP-C (p < 0.001). When the use of IgG
      avidity as a diagnostic tool for pneumococcal infection was evaluated, the
      highest discriminative power was found for StkP-C, followed by PcpA (area under
      the curve [95% confidence interval, CI]: 0.868 [0.759-0.977] and 0.743 [0.607
      879], respectively). The developed assay was robust and had no deleterious
      influence from multiplexing. Children with pneumococcal disease had lower median
      avidity against five pneumococcal proteins in the acute phase of disease compared
      to children without disease.

PMID- 29027029
TI  - 3-Hz postural tremor in multiple system atrophy cerebellar type (MSA-C)-a static
      posturography study.
AB  - The objective of the study is to evaluate postural dysfunction of multiple system
      atrophy-parkinsonian type (MSA-P) and cerebellar type (MSA-C) by static
      posturography exam. A total of 29 MSA-P patients, 40 MSA-C patients, and 23
      healthy controls (HC) were recruited and engaged in a sensory organization test
      (SOT). The amplitude of the postural sway was measured and transformed into
      energy value by Fourier analyzer. SOT scores, frequency of falls and typical 3-Hz
      postural tremors during the four stance tasks, and energy value in three
      different frequency bands were recorded and compared. Compared with HC, SOT
      scores were significantly lower in MSA groups (P < 0.01). Compared with MSA-P,
      the vestibular scores were further reduced in MSA-C patients (P < 0.05). Falls
      were more frequent in MSA groups, especially in SOT4 task (foam surface with eyes
      closed) or in MSA-C group (P < 0.05). Typical 3-Hz postural tremor was observed
      in 97.5% MSA-C patients, in 24.1% MSA-P patients but in none of the HC (P <
      0.05). Compared with HC, much more energy was consumed in every task, every
      direction, and nearly every frequency band in MSA groups. Energy value of MSA-C
      group was significantly higher than that of MSA-P, especially in higher frequency
      band (2 ~ 20 Hz) or in more difficult stance tasks (SOT 3 ~ 4, foam surface with
      eyes open or closed) (P < 0.05). Both MSA-P and MSA-C were characterized by
      severe static postural dysfunction. However, typical 3-Hz postural tremor was
      predominant in MSA-C and was very useful in the differential diagnosis between
      MSA-P and MSA-C.

PMID- 29027030
TI  - Diagnostic accuracy of fungal identification in histopathology and cytopathology
      specimens.
AB  - Tools to diagnose fungal infection are microscopic examination, antigen or
      antibody-based detection tests, molecular diagnostics, and culture, with culture
      being the "gold standard" for species-level identification. Although these
      methods are commonly used in concert and yield concordant results, in some cases
      tissue is not available for culture, and/or different methodologies yield
      discrepant results. These discrepancies may be clinically significant, causing
      confusion and inappropriate or delayed initiation of antifungals. This study
      evaluates the correlation between microscopic examination and the results of
      laboratory studies, and identifies clinical scenarios and specimen
      characteristics associated with tissue sent for microscopic examination without
      concomitant laboratory studies. We performed an 18-year retrospective review at a
      tertiary-care, academic medical center in the Midwest United States of all fungal
      infection diagnoses made by microscopic examination. Only 16% of samples with
      fungal infection diagnosed by microscopic examination had a concomitant sample
      submitted for laboratory studies. Of these cases, 36% had no growth on culture
      and/or had a negative laboratory study. Among cases in which fungal infections
      were diagnosed and laboratory studies were positive, the accuracy of
      histopathologic identification was 95%. The most common cause for incorrect
      morphologic diagnoses was misidentification of Aspergillus spp. and Mucorales.
      Our results underscore the importance of educating pathologists with regard to
      appropriate terminology and increasing knowledge of mycology, particularly in
      relation to organisms forming hyphae in tissue. Species-level diagnosis of fungi
      cannot be made by microscopic examination of tissue alone. Anatomic pathology
      reports should recommend correlation with laboratory studies, and provide a
      differential diagnosis based on morphology.

PMID- 29027031
TI  - Low-level laser irradiation induces in vitro proliferation of stem cells from
      human exfoliated deciduous teeth.
AB  - The aim of this study was to evaluate the effect of low-level laser irradiation
      (LLLI) on the proliferation and viability of stem cells from human exfoliated
      deciduous teeth (SHED). Cells were irradiated or not (control) with an InGaAlP
      laser diode (660 nm, 30 mW, continuous action mode) using two different energy
      densities (0.5 J/cm2-16 s; 1.0 J/cm2-33 s). Irradiation was performed at 0 and 48
      h, with the laser probe fixed at a distance of 0.5 cm from the cells. Cell
      proliferation was analyzed at 0, 24, 48, and 72 h by the Trypan blue exclusion
      method and MTT assay. Cell cycle and Ki67 expression were analyzed by flow
      cytometry. Apoptosis-related events were evaluated by expression of annexin V/PI
      and nuclear morphological changes by staining with DAPI. Differences between
      groups at each time were analyzed by the Kruskal-Wallis and Mann-Whitney tests,
      adopting a level of significance of 5% (p < 0.05). The results showed that an
      energy density of 1.0 J/cm2 promoted an increase in cell proliferation at 48 and
      72 h compared to the control and 0.5 J/cm2 groups. Cell cycle analysis revealed a
      predominance of cells in the S and G2/M phases in the irradiated groups. This
      finding was confirmed by the increased expression of Ki67. Low positive staining
      for annexin V and PI was observed in all groups, and no nuclear changes were
      detected, indicating that cell viability was not affected by the energy densities
      tested. It can be concluded that the LLLI parameters used (660 nm, 30 mW, 1.0
      J/cm2) promote the proliferation of SHEDs and the maintenance of cell viability.

PMID- 29027032
TI  - Cocaine increases dopaminergic connectivity in the nucleus accumbens.
AB  - The development of addictive behavior is associated with functional and
      structural plasticity in the mesocorticolimbic pathway. Increased connectivity
      upon cocaine administration has been inferred from increases in dendritic spine
      density, but without observations of presynaptic elements. Recently, we
      established a method that enables analyses of both dendritic spines and
      glutamatergic boutons and presented evidence that cocaine induces changes in
      striatal connectivity. As the pharmacological and behavioral effects of cocaine
      directly implicate dopaminergic neurons and their afferents, a remaining question
      is whether dopaminergic striatal innervations also undergo structural plasticity.
      To address this issue, we generated transgenic mice in which the fluorophore
      tdTomato is expressed under the promoter of the dopamine transporter gene. In
      these mice, specific labeling of dopaminergic boutons was observed in the
      striatum. Of note, the accordance of our results for control mice with previous
      electron microscopy studies confirms that our method can be used to decipher the
      spatial organization of boutons in relation to dendritic elements. Following
      repeated cocaine administration that led to behavioral locomotor sensitization,
      an increased density of dopaminergic boutons was observed 1 day later in the
      nucleus accumbens shell specifically, and not in other striatal regions. Combined
      labeling of dopaminergic boutons and striatal dendrites showed that cocaine
      significantly increased the percentage of dendritic spines associated with a
      dopaminergic bouton. Our results show that chronic cocaine administration induces
      structural plasticity of dopaminergic boutons that could participate in dopamine
      dependent neuronal adaptations in the striatum.

PMID- 29027033
TI  - Auditory stimulus has a larger effect on anticipatory postural adjustments in
      older than young adults during choice step reaction.
AB  - PURPOSE: The study aim was to compare the influence of an auditory stimulus (AS)
      on anticipatory postural adjustments (APAs) between young and older adults during
      a choice step reaction. METHODS: Sixteen young and 19 older adults stepped
      forward in response to a visual imperative stimulus of an arrow. We used a choice
      reaction time (CRT) task and a Simon task which consisted of congruent and
      incongruent conditions. The direction of the presented arrow and its spatial
      location matched in the congruent condition while they did not in the incongruent
      condition. The AS was presented randomly and simultaneously with the visual
      stimulus. Incorrect weight shifts before lifting off the foot, termed APA errors,
      stepping errors, temporal parameters, and APA amplitudes were analyzed. RESULTS:
      The APA error rate was higher in trials with than without AS in all task
      conditions for the older group, while this increase occurred only in the
      incongruent condition for the young group. The stepping error rate was also
      increased in the presence of AS in the incongruent condition for the older group.
      Reaction times were faster with AS in both groups. The APA amplitude of erroneous
      APA trials became larger with AS in the incongruent condition for both groups,
      and this effect appeared greater for the older group. CONCLUSIONS: The effect of
      AS on APAs is larger in the elderly during a choice step reaction. In the
      presence of incongruent visual information, this effect becomes even greater,
      potentially inducing not only APA errors but also stepping errors.

PMID- 29027034
TI  - Low-intensity LED therapy (lambda 640 +/- 20 nm) on saphenectomy healing in
      patients who underwent coronary artery bypass graft: a randomized, double-blind
      study.
AB  - Myocardial revascularization surgery (CABG) is the most appropriate treatment for
      coronary artery disease. Currently, the great challenge is to reduce
      postoperative complications, such as wound infections, dehiscence, pain, and
      patients' quality of life. The saphenectomy is the target of complications in 10%
      of cases, which can cause greater morbidity, time, and cost of hospitalization.
      Studies show that low-intensity laser or light-emitted diode (LED) therapy
      promotes positive biomodulation of the tissue repair process, culminating in a
      lower incidence of dehiscence, pain reduction, and improvement in quality of
      life. The objective of the present study was to evaluate clinically the saphenous
      tissue repair after LED therapy. Forty subjects of both genders who underwent
      CABG with extracorporeal circulation were randomly divided into two groups: the
      placebo (PG) and experimental (EG). The experimental group underwent low
      intensity LED therapy (lambda 640 +/- 20 nm, 6 J/cm2) on saphenectomy. The tissue
      repair was analyzed by digital photogrammetry on the first and fifth
      postoperative day. The border closure was blindly evaluated by three researchers.
      The hematoma and hyperemia area was quantitatively analyzed using ImageJ(c)
      software. The results showed that in the experimental group, there were less
      bleeding points and no dehiscence in saphenectomy, as compared to the placebo
      group. There was also a smaller area of hematoma and hyperemia in the
      experimental group (p < 0.0009). These data lead to the conclusion that the type
      of phototherapy protocol employed can assist in tissue repair.

PMID- 29027035
TI  - No significant differences in short-term renal prognosis between living kidney
      donors with and without diabetes.
AB  - BACKGROUND: Renal prognosis in living kidney donors with diabetes is currently
      not known. In this study, we sought to investigate renal prognosis in living
      kidney donors with diabetes. METHODS: We retrospectively investigated 241 living
      kidney donors who underwent nephrectomy at Jichi Medical University Hospital
      between January 2000 and December 2015. Donors with a follow-up period of less
      than 1 year were excluded. The remaining donors were divided into a diabetic
      group and a non-diabetic group. Their clinical parameters before donation and
      renal prognosis after donation were compared. RESULTS: Of the 241 donors, 16 were
      excluded due to their follow-up period being less than 1 year. Of the remaining
      225 donors, 14 were diabetic and 211 were non-diabetic. There were no significant
      differences in variables at pre-donation. The median follow-up period was 4.3
      (1.5-10.7) and 4.6 (1.0-13.0) years in kidney donors with and without diabetes,
      respectively. At the end of follow-up, the estimated glomerular filtration rate
      was 51.7 +/- 7.1 ml/min/1.73 m2 in the diabetic group and 52.1 +/- 12.2
      ml/min/1.73 m2 (p = 0.906) in the non-diabetic group; urine albumin excretion was
      9.5 (2-251) mg/day (or mg/g creatinine) in the diabetic group and 6 (0-626)
      mg/day (or mg/g creatinine) in the non-diabetic group (p = 0.130); and urine
      protein excretion was 0.079 (0-0.41) g/day in the diabetic group and 0.051 (0
      3.7) g/day in the non-diabetic group (p = 0.455). CONCLUSIONS: There were no
      significant differences in short-term renal prognosis between kidney donors with
      and without diabetes.

PMID- 29027036
TI  - Risk factors of ceftriaxone-associated biliary pseudolithiasis in adults:
      influence of renal dysfunction.
AB  - BACKGROUND: Ceftriaxone (CTRX) is a known cause of biliary pseudolithiasis (BPL)
      mainly in children. Biliary elimination of CTRX increases in patients with renal
      dysfunction. However, the influence of renal dysfunction on the incidence of CTRX
      associated BPL has not been well investigated. The aim of this study was to
      investigate the cumulative incidence of CTRX-associated BPL in adults and to
      assess if renal dysfunction is a risk factor. METHODS: We retrospectively
      analyzed the medical records of 478 patients treated with CTRX to assess the
      incidence and risk factors of CTRX-associated BPL. We examined age, sex, body
      weight, dosage, and duration of CTRX therapy, and the concentrations of serum
      creatinine, estimated glomerular filtration rate (eGFR), albumin, and serum
      calcium in all the patients. The cumulative incidence of BPL was calculated using
      a competing risk model. The multivariate analysis of each variable for the
      development of BPL was assessed by a Cox proportional hazards model. RESULTS: A
      total of 362 patients (75.7%) had renal dysfunction (eGFR: < 60 mL/min). The
      cumulative incidence of BPL in patients with renal dysfunction was significantly
      higher than that in patients with normal kidney function (4.1 vs. 0.6%, p =
      0.017). Renal dysfunction (Hazard ratio (HR) 8.14, 95% CI 1.05-63.0, p = 0.045)
      and female sex (HR 5.35, 95% CI 1.17-24.5, p = 0.031) were independent risk
      factors of CTRX-associated BPL, which was confirmed using multivariate analysis
      (renal dysfunction: HR 7.93, 95% CI 1.04-60.5, p = 0.046) (female sex HR 4.65,
      95% CI 1.03-21.1, p = 0.046). CONCLUSIONS: Renal dysfunction is an independent
      risk factor of CTRX-associated BPL in adults.

PMID- 29027037
TI  - Optimal surface property for three-dimensional echo visualization.
AB  - PURPOSE: Three-dimensional (3D) echo is a useful modality to guide off-pump
      intracardiac surgery, and this study aimed to determine the optimal surface
      property for minimizing echo dropout and grating lobes. METHODS: A total of 13
      specimens were examined. The specimens were scanned while they were rotated from
      0 degrees  to 90 degrees , and en face views were recorded in the 3D zoom mode.
      Changes in brightness were compared with the surface profile, which was traced
      from microscopic images. The brightness and size of grating lobes were also
      examined. RESULTS: Decreases in brightness that were observed at a large rotation
      angle were classified into three groups (sharp, moderate, and gradual), and
      variation in the effective reflective plane size appeared to be a major
      determinant of this property. The same material showed different degrees of
      reflection depending on the surface profile. The size of grating lobes was
      affected by variation in the reflective plane size, but not by the intensity of
      reflection. The brightness of the grating lobes was similar among specimens.
      CONCLUSIONS: These results suggest that echo dropout and grating lobes can be
      effectively eliminated by an appropriate surface profile; thus, a likely
      practical solution would be to manufacture a surface that provides an adequate
      reflective surface size at various incident angles.

PMID- 29027038
TI  - Rescue of Outer Hair Cells with Antisense Oligonucleotides in Usher Mice Is
      Dependent on Age of Treatment.
AB  - The absence of functional outer hair cells is a component of several forms of
      hereditary hearing impairment, including Usher syndrome, the most common cause of
      concurrent hearing and vision loss. Antisense oligonucleotide (ASO) treatment of
      mice with the human Usher mutation, Ush1c c.216G>A, corrects gene expression and
      significantly improves hearing, as measured by auditory-evoked brainstem
      responses (ABRs), as well as inner and outer hair cell (IHC and OHC) bundle
      morphology. However, it is not clear whether the improvement in hearing achieved
      by ASO treatment involves the functional rescue of outer hair cells. Here, we
      show that Ush1c c.216AA mice lack OHC function as evidenced by the absence of
      distortion product otoacoustic emissions (DPOAEs) in response to low-, mid-, and
      high-frequency tone pairs. This OHC deficit is rescued by treatment with an ASO
      that corrects expression of Ush1c c.216G>A. Interestingly, although rescue of
      inner hairs cells, as measured by ABR, is achieved by ASO treatment as late as 7
      days after birth, rescue of outer hair cells, measured by DPOAE, requires
      treatment before post-natal day 5. These results suggest that ASO-mediated rescue
      of both IHC and OHC function is age dependent and that the treatment window is
      different for the different cell types. The timing of treatment for congenital
      hearing disorders is of critical importance for the development of drugs such ASO
      29 for hearing rescue.

PMID- 29027040
TI  - Actor-network theory and the OSCE: formulating a new research agenda for a post
      psychometric era.
AB  - The Objective Structured Clinical Examination (OSCE) is a ubiquitous part of
      medical education, although there is some debate about its value, particularly
      around possible impact on learning. Literature and research regarding the OSCE is
      most often situated within the psychometric or competency discourses of
      assessment. This paper describes an alternative approach: Actor-network-theory
      (ANT), a sociomaterial approach to understanding practice and learning. ANT
      provides a means to productively examine tensions and limitations of the OSCE, in
      part through extending research to include social relationships and physical
      objects. Using a narrative example, the paper suggests three ANT-informed
      insights into the OSCE. We describe: (1) exploring the OSCE as a holistic
      combination of people and objects; (2) thinking about the influences a checklist
      can exert over the OSCE; and (3) the implications of ANT educational research for
      standardisation within the OSCE. We draw from this discussion to provide a
      practical agenda for ANT research into the OSCE. This agenda promotes new areas
      for exploration in an often taken-for-granted assessment format.

PMID- 29027042
TI  - "Sex in a Relationship" versus "Sex During a One-Night Stand": The Link Between
      Mental Representations of Consensual Sexuality, Mating Strategies, and Sexual
      Experience in Heterosexual Women and Men.
AB  - Sexual scripts, that is, the mental representations of sexual behavior, are
      highly influenced by mating strategies and sexual experience. The relationship
      between these factors and sexual scripts is, however, poorly understood.
      Therefore, we assessed how long-term (e.g., "sex in a relationship") and short
      term (e.g., "one-night stand") strategies, as well as experience with highly
      scripted sexual practices (BDSM: bondage-discipline, dominance-submission, sadism
      masochism), influence verbalized sexual script composition and detailedness. To
      this end, 204 heterosexual men and women generated both a "sex in a relationship"
      and a "one-night stand" script. Regarding mating strategies, both men and women
      generated shorter "sex in a relationship" scripts than "one-night stand" scripts,
      due to a shorter approach (flirting) phase. In addition, in the "sex in a
      relationship" script, women generated longer foreplay phases than men. Regarding
      sexual experience, in the "sex in a relationship" script, individuals with high
      BDSM experience generated longer foreplay phases than individuals with middle- or
      low-BDSM experience. This pattern was reversed in the "one-night stand" script.
      These results provide empirical support for interactions between mating
      strategies and individual experience with regard to the mental representations of
      sexual activity and gender behavior. Understanding this relationship may enable
      us to better predict sexual encounters and may help to prevent conflicting or
      abusive situations.

PMID- 29027039
TI  - Patterns of Alcohol Abuse, Depression, and Intimate Partner Violence Among
      Township Mothers in South Africa Over 5 Years.
AB  - Alcohol is a major contributor to the global burden of disease. In South Africa,
      alcohol abuse is hypothesized to correlate with women's HIV status, mental
      health, and partner relationships over time. All pregnant women in 12 urban, low
      income, Cape Town neighborhoods were interviewed at baseline, post-birth, and at
      6, 12, 36, and 60 months following delivery with retention rates from 82.5 to
      94%. Women were assessed for any alcohol use, problematic drinking, depression,
      intimate partner violence, and HIV status. Prior to pregnancy discovery and 5
      years after giving birth, alcohol use was 25.8 and 24.7%, respectively. Most
      women decreased their alcohol use during pregnancy. Twenty-one percent reported
      alcohol use on two or more assessments, and only 15% of the mothers drinking
      alcohol at 5 years were also drinking at baseline. Mothers with depression had a
      higher likelihood of drinking alcohol compared to mothers who were not depressed
      only at baseline and 6 months post-birth. Mothers who experienced IPV had more
      than twice the likelihood of drinking alcohol compared to non-IPV mothers at all
      assessments. HIV positive mothers were more likely to drink alcohol compared to
      mothers without HIV prior to pregnancy discovery and at 5 years post-birth. These
      longitudinal trends in alcohol use among young women in South Africa represent a
      large economic, social, and health burden and must be addressed in a
      comprehensive manner.

PMID- 29027041
TI  - Increased hepatic fatty acid polyunsaturation precedes ectopic lipid deposition
      in the liver in adaptation to high-fat diets in mice.
AB  - OBJECTIVE: We monitored hepatic lipid content (HLC) and fatty acid (FA)
      composition in the context of enhanced lipid handling induced by a metabolic high
      fat diet (HFD) challenge and fasting. MATERIALS AND METHODS: Mice received a
      control diet (10% of kilocalories from fat, N = 14) or an HFD (45% or 60% of
      kilocalories from fat, N = 10 and N = 16, respectively) for 26 weeks. A subset of
      five mice receiving an HFD (60% of kilocalories from fat) were switched to the
      control diet for the final 7 weeks. At nine time points, magnetic resonance
      spectroscopy was performed in vivo at 14.1 T, interleaved with glucose tolerance
      tests. RESULTS: Glucose intolerance promptly developed with the HFD, followed by
      a progressive increase of fasting insulin level, simultaneously with that of HLC.
      These metabolic defects were normalized by dietary reversal. HFD feeding
      immediately increased polyunsaturation of hepatic FA, before lipid accumulation.
      Fasting-induced changes in hepatic lipids (increased HLC and FA polyunsaturation,
      decreased FA monounsaturation) in control-diet-fed mice were not completely
      reproduced in HFD-fed mice, not even after dietary reversal. CONCLUSION: A
      similar adaptation of hepatic lipids to both fasting and an HFD suggests common
      mechanisms of lipid trafficking from adipose tissue to the liver. Altered hepatic
      lipid handling with fasting indicates imperfect metabolic recovery from HFD
      exposure.

PMID- 29027043
TI  - Clinical, psychological features and quality of life of fibromyalgia patients: a
      cross-sectional study of Chinese sample.
AB  - This study aimed to determine the clinical, psychological features, and quality
      of life in Chinese fibromyalgia (FM) patients who fulfilled the American College
      of Rheumatology (ACR) 2010 FM classification criteria at initial diagnosis. A
      cross-sectional study was carried out in the Chinese People's Liberation Army
      (PLA) General Hospital. A hundred and seven Chinese FM patients (86 females, 21
      males) were included. Eighty-six patients completed the questionnaires.
      Descriptive, differences, and correlation analyses were performed. The results
      showed that Chinese FM patients started their diseases at a median age of 37
      years, with a male-to-female ratio of 1:4.1. Most patients were diagnosed about 2
      years after symptoms onset. Nearly 60 % (59.81%) patients had less than college
      education, 58.88% did not have a full-time job, and 41.12% had low-back pain. Out
      of 86 patients, 58 (67.4%) had anxiety and 75 (87.2%) had depression. FM patients
      had poor quality of life in each aspect and deficient social support. The level
      of pain for the past 7 days was strongly correlated with patient global
      impression of severity (PGI-S; r = 0.651, p < 0.001) and patient global
      impression of bother (PGI-B; r = 0.628, p < 0.001). PGI-B was correlated with
      seven subscales of short-form health survey (SF-36). The study demonstrated the
      clinical, psychological features of Chinese patients. The diagnosis was delayed
      for about 2 years. Most of the patients had anxiety and depression, had poor
      quality of life, and lacked proper social support. PGI-B might be a simple
      measurement to evaluate patients' quality of life.

PMID- 29027044
TI  - Crude glycerol from biodiesel as a carbon source for production of a recombinant
      highly thermostable beta-mannanase by Pichia pastoris.
AB  - OBJECTIVE: To explore an efficient use of crude glycerol for the production of a
      highly thermostable beta-mannanase (ReTMan26) by Pichia pastoris X33. RESULTS:
      Cell growth was significantly inhibited by 4 and 6% (w/v) crude glycerol in 250
      ml shake-flasks and in 5 l bioreactor batch cultures, respectively, but not
      affected by pure glycerol at the same concentrations. For further study, the
      impact of various impurities in crude glycerol on the cell growth of, and
      ReTMan26 production by, Pichia pastoris was investigated. Salts and methanol did
      not exert an inhibitory effect, but >= 0.2% and 0.3% (w/v) soap in shake-flask
      and bioreactor cultures, respectively, inhibited fermentation. Under identical
      conditions, the biomass and ReTMan26 activity produced by high-cell-density
      fermentation using 5% crude glycerol (glycerol at 80%, w/w) were slightly higher
      than those using 4% (w/v) pure glycerol. CONCLUSIONS: Non-pretreated <= 5% (w/v)
      crude glycerol could be effectively utilized for industrial production of
      ReTMan26, and the total production costs using crude glycerol were ~ 4.2% lower
      than those using pure glycerol.

PMID- 29027046
TI  - Contamination levels and human health risk assessment of toxic heavy metals in
      street dust in an industrial city in Northwest China.
AB  - This study investigated the content, distribution, and contamination levels of
      toxic metals (Cd, Cr, Cu, Pb, and Zn) in street dust in Lanzhou, an industrial
      city in Northwest China. Meanwhile, the risk these metals posed to the urban
      ecosystem and human health was also evaluated using the potential ecological risk
      index and human exposure model. Results showed that concentrations of these
      metals in the dust are higher than the background value of local soil, with Cu
      having the highest levels. The districts of Anning and Xigu had the most extreme
      levels of contamination, while Chengguan and Qilihe districts were lightly
      contaminated, which can be partly attributed to human activities and traffic
      densities. In comparison with the concentrations of selected metals in other
      cities, the concentrations of heavy metals in Lanzhou were generally at moderate
      or low levels. Heavy metal concentration increased with decreasing dust particle
      size. The pollution indices of Cr, Cd, Cu, Pb, and Zn were in the range of 0.289
      2.09, 0.332-2.15, 1.38-6.21, 0.358-2.59, and 0.560-1.83 with a mean of 1.37,
      1.49, 3.18, 1.48, and 0.897, respectively. The geo-accumulation index (I geo)
      suggested that Zn in street dust was of geologic origin, while Cd, Cr, Pb, and Cu
      were significantly impacted by anthropogenic sources. The comprehensive pollution
      index showed that urban dust poses a high potential ecological risk in Lanzhou.
      Non-carcinogenic and carcinogenic effects due to exposure to urban street dust
      were assessed for both children and adults. For non-carcinogenic effects,
      ingestion appeared to be the main route of exposure to dust particles and thus
      posed a higher health risk to both children and adults for all metals, followed
      by dermal contact. Hazard index values for all studied metals were lower than the
      safe level of 1, and Cr exhibited the highest risk value (0.249) for children,
      suggesting that the overall risk from exposure to multiple metals in dust is low.
      The carcinogenic risk for Cd and Cr was all below the acceptable level (< 10-6).

PMID- 29027047
TI  - Soil color indicates carbon and wetlands: developing a color-proxy for soil
      organic carbon and wetland boundaries on sandy coastal plains in South Africa.
AB  - A relationship between soil organic carbon and soil color is acknowledged-albeit
      not a direct one. Since heightened carbon contents can be an indicator of
      wetlands, a quantifiable relationship between color and carbon might assist in
      determining wetland boundaries by rapid, field-based appraisal. The overarching
      aim of this initial study was to determine the potential of top soil color to
      indicate soil organic carbon, and by extension wetland boundaries, on a sandy
      coastal plain in South Africa. Data were collected from four wetland types in
      northern KwaZulu-Natal in South Africa. Soil samples were taken to a depth of 300
      mm in three transects in each wetland type and analyzed for soil organic carbon.
      The matrix color was described using a Munsell soil color chart. Various color
      indices were correlated with soil organic carbon. The relationship between color
      and carbon were further elucidated using segmented quantile regression. This
      showed that potentially maximal carbon contents will occur at values of low color
      indices, and predictably minimal carbon contents will occur at values of low or
      high color indices. Threshold values can thus be used to make deductions such as
      "when the sum of dry and wet Value and Chroma values is 9 or more, carbon content
      will be 4.79% and less." These threshold values can then be used to differentiate
      between wetland and non-wetland sites with a 70 to 100% certainty. This study
      successfully developed a quantifiable correlation between color and carbon and
      showed that wetland boundaries can be determined based thereon.

PMID- 29027048
TI  - Export fluxes of geochemical solutes in the meltwater stream of Sutri Dhaka
      Glacier, Chandra basin, Western Himalaya.
AB  - The hydrochemistry of meltwater from the Sutri Dhaka Glacier, Western Himalaya,
      has been studied to understand the influence of the factors controlling the
      weathering processes of the glaciers during the peak ablation period. The high
      solar irradiance prompted intense melting, which has raised the stream flow of
      the glacier. The meltwater has been observed as slightly alkaline (mean pH 8.2)
      and contains the major anions (HCO3- > SO42- > NO3- > Cl-) and cations (Ca2+ >
      Mg2+ > K+ > Na+ > NH4+) with Ca2+ (78.5%) and HCO3- (74.5%) as the dominant
      species. The piper diagram indicates the category of stream meltwater as Ca2+
      HCO3- type. In addition, it is evident from the Gibbs diagram that the
      interaction between the meltwater and bedrock controls the ionic concentrations
      of the glacial meltwater. The high ratio value (~ 0.75) of HCO3-/(HCO3- + SO42-)
      indicates that the carbonate weathering is dominant. Fe and Al followed by Mn,
      Sr, and Ti are the most dominant trace elements present in the meltwater. The
      significant negative correlation exhibited by the major ions and Sr with the
      discharge is recommended for the enrichment of these solutes during the lean
      discharge periods. However, the insignificant correlation of Fe, Al, Mn, and Ti
      with discharge suggests their physicochemical control. The principal component
      analysis (PCA) carried has highlighted three dominant composites, i.e., the water
      rock interaction, atmospheric dust inputs, and physicochemical changes in the
      meltwater. Hence, the present study elucidates the export of geochemical solutes
      from Sutri Dhaka Glacier and factors governing the water chemistry, which helps
      in the better understanding of hydrochemical processes of the Himalayan glaciers
      and substantial improvement of our understanding about the glacio-hydrological
      environments and their response in the scenario of global warming.

PMID- 29027045
TI  - Characteristics of patients with fragility hip fractures in the northern Kyushu
      district in Japan: a multicenter prospective registry based on an electronic data
      capture system.
AB  - Osteoporosis has become a worldwide public health problem, in part due to the
      fact that it increases the risk of fragility hip fractures (FHFs). The
      epidemiological assessment of FHFs is critical for their prevention; however,
      datasets for FHFs in Japan remain scarce. This was a multicenter, prospective,
      observational study in the northern district of Kyushu Island. Inclusion criteria
      were age > 60 years with a diagnosis of FHF and acquisition of clinical data by
      an electronic data capture system. Of 1294 registered patients, 1146 enrolled in
      the study. Nearly one third of patients (31.8%) had a history of previous
      fragility fractures. The percentage of patients receiving osteoporosis treatment
      on admission was 21.5%. Almost all patients underwent surgical treatment (99.1%),
      though fewer than 30% had surgery within 48 h after hospitalization. Bone mineral
      density (BMD) was evaluated during hospitalization in only 50.4% of patients. The
      rate of osteoporosis treatment increased from 21.5% on admission to 39.3% during
      hospitalization. The main reasons that prescribers did not administer
      osteoporosis treatment during hospitalization were forgetfulness (28.4%) and
      clinical judgment (13.6%). Age and female ratio were significantly higher in
      patients with previous FHFs than in those without. There was a significant
      difference in the rate of osteoporosis treatment or L-spine BMD values in
      patients with or without previous FHFs on admission. In conclusion, this study
      confirmed that the evaluation and treatment of osteoporosis and FHFs is still
      suboptimal in Japan, even in urban districts.

PMID- 29027049
TI  - Acute phase dynamics of circulating tumor cells after paclitaxel and doxorubicin
      chemotherapy in breast cancer mouse models.
AB  - PURPOSE: Circulating tumor cells (CTCs) can provide a potentially minimal
      invasive source for monitoring chemotherapeutic effects. However, detailed in
      vivo dynamics of CTC after chemotherapy remain largely unknown. METHODS: We
      monitored CTC number and morphology early after chemotherapy using a newly
      developed cytology-based CTC detection device and triple-negative breast cancer
      mouse CTC models with spontaneous lung metastatic potential. RESULTS: Paclitaxel
      inhibited cell growth of breast cancer cells by mainly G2/M cell cycle arrest and
      partly apoptosis, whereas doxorubicin inhibited cell growth mainly by apoptosis
      and partly G2 cell cycle arrest in vitro. The number of CTCs was significantly
      increased 3-10 days after paclitaxel and doxorubicin chemotherapy and decreased
      thereafter in two mouse CTC models. The transiently increased CTCs early post
      chemotherapy consisted of not only G2/M arrested cells (apoptotic cells), but
      also morphologically near-intact live cells. This heterogeneous cell population
      of CTCs was similar to that of primary tumor tissue after chemotherapy.
      CONCLUSIONS: These results indicate that CTCs can be mobilized from the primary
      tumor in rapid response to chemotherapy and suggest the possibility that CTC
      monitoring from both numerical and morphological viewpoints early after
      chemotherapy using a cytology-based CTC detection device would be a useful
      diagnostic tool for predicting drug sensitivity/resistance in preclinical and
      clinical setting.

PMID- 29027050
TI  - Characterization and origin of organic and inorganic pollution in urban soils in
      Pisa (Tuscany, Italy).
AB  - We assessed the quality of 31 urban soils in Pisa by analyzing total petroleum
      hydrocarbons (TPHs), Cd, Cr, Cu, Hg, Mn, Ni, Pb, Zn, and the platinum group
      elements (PGEs). The risk was evaluated by the geological accumulation index (I
      geo) and the enrichment factor (EF). Results were compared with those obtained
      from a non-urban site and with the quantitative limits fixed by Italian
      legislation. In nearly all the monitored sites, the legal limit for TPH of 60
      mg/kg in residential areas was exceeded, indicating widespread and intense
      pollution throughout the entire city area. The I geo indicated no Cd, Cu, Mn, Ni,
      and Zn pollution and minimal Pb and Cr pollution due to anthropogenic enrichment.
      Legal Hg and Zn limits of 1 and 150 mg/kg, respectively, were exceeded in about
      20% of sites; Cd (2 mg/kg), Cr (150 mg/kg), and Cu (120 mg/kg) in only one site;
      and the Ni legal limit of 120 mg/kg was never exceeded. Some urban soils showed a
      higher Hg level than the more restrictive legal limit of 5 mg/kg concerning areas
      for industrial use. Based on the soluble, exchangeable, and carbonate-bound
      fractions, Mn and Zn showed the highest mobility, suggesting a more potential
      risk of soil contamination than the other metals. The TPH and both Cr and Hg
      amounts were not correlated with any of the other monitored metals. The total
      contents of Cd, Pb, Zn, and Cu in soils were positively correlated with each
      other, suggesting a common origin from vehicular traffic. The PGE values (Pt and
      Pd) were below the detection limits in 75%-90% of the monitored areas, suggesting
      that their accumulation is at an early stage.

PMID- 29027051
TI  - Cell response of flexible PMMA-derivatives: supremacy of surface chemistry over
      substrate stiffness.
AB  - The present work reports on the development of a range of poly(methyl
      methacrylate)/poly(ethylene glycol) (PMMAPEG)-based materials, characterized by
      different elasticity moduli in order to study the influence of the substrate's
      mechanical properties on the response of human umbilical vein endothelial cells
      (HUVECs). To render the selected materials cell-interactive, a polydopamine
      (PDA)/gelatin type B (Gel B) coating was applied. Prior to the in vitro assay,
      the success of the PDA and Gel B immobilization onto the materials was confirmed
      using X-ray photoelectron spectroscopy (XPS) as reflected by the nitrogen
      percentages measured for the materials after PDA and Gel B deposition. Tensile
      tests showed that materials with E-moduli ranging from 37 to 1542 MPa could be
      obtained by varying the ratio between PMMA and PEG as well as the PEG molecular
      weight and its functionality (i.e. mono-methacrylate vs. di-methacrylate). The
      results after 1 day of cell contact suggested a preferred HUVECs cell growth onto
      more rigid materials. After 1 week, the material with the lowest E-modulus of 37
      MPa showed lower cell densities compared to the other materials. No clear
      correlation could be observed between the number of focal adhesion points and the
      substrate stiffness. Although minor differences were found, these were not
      statistically significant. This last conclusion again highlights the universal
      character of the PDA/Gel B modification. The present work could thus be valuable
      for the development of a range of cell substrates requiring different mechanical
      properties in line with the envisaged application while the cell response should
      ideally remain unaffected.

PMID- 29027052
TI  - Geochemical fingerprints of "Prosecco" wine based on major and trace elements.
AB  - The terroir can be defined as interactive ecosystem that includes climate,
      geology, soil and grapevine, and it is used to explain the hierarchy of high
      quality of wine. In order to understand the terroir functions, it is necessary to
      analyse the interactions among the geology, soil and wine. To define a
      geochemical fingerprint, the relationship between geochemistry of vineyard soil
      and chemical composition of wine from Veneto Italian Region was studied. The
      vineyards tested belonged to four distinct wineries located in the Veneto
      alluvial plain, included in the Controlled Designation of Origin (DOC) area of
      Prosecco. We investigated the relationship between major and trace elements in
      soil and their concentrations in Prosecco wine according to geographical origin.
      The detection of chemical composition in soil and wine were analysed by
      inductively coupled plasma mass spectrometry, and data were elaborated by
      nonparametric test and multivariate statistics Linear Discrimination Analysis.
      The geochemical and statistical analyses allowed to discriminate the vineyard
      soils according to geo-lithological characteristics of each area and to identify
      the geochemical "Prosecco" fingerprints, useful against fraudulent use of DOC
      wine labels.

PMID- 29027054
TI  - Capsular bag irrigation using 0.025% povidone-iodine in balanced salt solution
      PLUS for the treatment of postoperative endophthalmitis.

PMID- 29027053
TI  - Public Health Considerations Associated with the Location and Operation of Off
      Leash Dog Parks.
AB  - Off-leash dog parks may enhance human health, but may also lead to health risk
      through infection or canine aggression. Published evidence was reviewed to
      examine positive and negative public health impacts of off-leash dog parks, as
      well as strategies for enhancing benefits and mitigating risks. Evidence suggests
      that off-leash dog parks can benefit physical and social health, as well as
      community connectedness. While studies have documented shedding of zoonotic
      agents in dog parks, the risk of transmission to humans is relatively unknown.
      Evidence on the risk of dog bites in off-leash dog parks is also limited. Case
      examples from North American off-leash dog parks highlight the importance of park
      location/design, public adherence to safe and hygienic practices, and effective
      regulatory strategies for mitigating potential risks and maximizing the benefits
      of off-leash dog parks.

PMID- 29027055
TI  - Socio-demographic characters, distribution and transformation of iodine in soil,
      plant and wheat grains at District Diamer, Gilgit-Baltistan, Pakistan.
AB  - Iodine deficiency in soils and plants is a common problem in the hilly areas and
      has still been ignored. The aim of the current study is to investigate associated
      health issues, socio-economic characteristics and people's perception regarding
      iodine deficiency. Furthermore, a follow-up study was conducted to determine
      iodine and nutrients concentration in soil and crops at District Diamer, Gilgit
      Baltistan, Pakistan. A descriptive and empirical analysis was examined. Most
      importantly, male was significantly observed as more affected for iodine
      deficiency than female, as contrary to the literature, socio-economic factors
      such as households' income and awareness (education) are reported as negative and
      significant contributor to reduce the iodine deficiency among the people
      irrespective of the gender. Majority of people (84%) heard about the iodine, but
      about 51.6% people argue that iodine has no effect on the human body and 56% of
      the respondents do not know why iodine is necessary for human. It was found that
      11.5% of the community was affected from the IDD and majority of them were
      females. Wheat crops were the principal crop since it supplies 75% of calorific
      energy in an average Pakistani diet. The concentrations of iodine in soil samples
      range from 4.21 to 5.45 mg kg-1. The concentration of iodine in wheat crop plant
      sampled were considerably varied as Boner > Gais > Goher Abad with 1.12, 0.91 and
      0.81 mg kg-1. respectively. Likewise, grain iodine concentration was varied as
      Gais > Boner > Goher Abad with 0.126, 0.102 and 0.078 mg kg-1, respectively. This
      study exposed that community using the cereal crops could face iodine deficiency
      in their diet which can cause endemic goiter among the population and control the
      iodine deficiency by empowering the rural community to raise the income level and
      providing the awareness to the people.

PMID- 29027057
TI  - Comparative analysis of mean retinal thickness measured using SD-OCT in normal
      young or old age and glaucomatous eyes.
AB  - PURPOSE: To evaluate changes in macular thickness, ganglion cell layer/inner
      plexiform layer (GCL/IPL) thickness, and retinal nerve fiber layer (RNFL)
      thickness in normal eyes and glaucomatous eyes using spectral domain optical
      coherence tomography (SD-OCT). METHODS: We enrolled 89 eyes (all left eyes),
      including 45 (of 45 patients) eyes with glaucoma and 44 (of 44 patients) normal
      eyes. The data from macular measurements using spectral domain optical coherence
      tomography were analyzed according to groups divided by age and glaucoma status.
      The macular thickness analysis, GCL/IPL thickness, and RNFL thickness values
      determined by SD-OCT scans were compared among the groups. RESULTS: Mean macular
      thickness decreased significantly with age or glaucoma. Mean GCL/IPL thickness
      decreased significantly in glaucomatous eyes in all sectors but did not decrease
      with age. Mean RNFL thickness, which was divided into four quadrants (superior,
      nasal, inferior, and temporal), decreased significantly in glaucomatous eyes at
      all quadrants and decreased in the temporal quadrant with age in non-glaucomatous
      eyes. No significant differences were detected between eyes with normal tension
      glaucoma (NTG) and primary open angle glaucoma (POAG) in all sectors of mean
      GCL/IPL thickness, RNFL thickness, and macular thickness. CONCLUSIONS: No
      significant difference in mean thickness was detected between eyes with NTG and
      POAG. Some of the sectors of RNFL thickness decreased with age or glaucoma.
      GCL/IPL thickness, however, decreased in glaucomatous eyes but not with age.
      Therefore, GCL/IPL thickness is less influenced by age when monitoring patients
      with glaucoma or suspect glaucoma.

PMID- 29027056
TI  - Curcumin affords neuroprotection and inhibits alpha-synuclein aggregation in
      lipopolysaccharide-induced Parkinson's disease model.
AB  - Parkinson's disease (PD) pathology is characterized by the abnormal accumulation
      and aggregation of the pre-synaptic protein alpha-synuclein in the dopaminergic
      neurons as Lewy bodies (LBs). Curcumin, which plays a neuroprotective role in
      various animal models of PD, was found to directly modulate the aggregation of
      alpha-synuclein in in vitro as well as in in vivo studies. While curcumin has
      been shown to exhibit strong anti-oxidant and anti-inflammatory properties, there
      are a number of other possible mechanisms by which curcumin may alter alpha
      synuclein aggregation which still remains obscure. Therefore, the present study
      was designed to understand such concealed mechanisms behind neuroprotective
      effects of curcumin. An animal model of PD was established by injecting
      lipopolysaccharide (LPS, 5 ug/5 ul PBS) into the substantia nigra (SN) of rats
      which was followed by curcumin administration (40 mg/kg b.wt (i.p.)) daily for a
      period of 21 days. Modulatory functions of curcumin were evident from the
      inhibition of astrocytic activation (GFAP) by immunofluorescence and NADPH
      oxidase complex activation by RT-PCR. Curcumin supplementation prevented the LPS
      induced upregulation in the protein activity of transcription factor NFkappaB,
      proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-1alpha), inducible nitric
      oxide synthase (iNOS) as well as the regulating molecules of the intrinsic
      apoptotic pathway (Bax, Bcl-2, Caspase 3 and Caspase 9) by ELISA. Curcumin also
      resulted in significant improvement in the glutathione system (GSH, GSSG and
      redox ratio) and prevented iron deposition in the dopaminergic neurons as
      depicted from atomic absorption spectroscopy (AAS) and Prussian blue staining,
      respectively. Curcumin also prevented alpha-synuclein aggregates in the
      dopaminergic neurons as observed from gene as well as protein activity of alpha
      synuclein using RT-PCR and IHC. Collectively, our results suggest that curcumin
      can be further pursued as a candidate drug in the molecules targeted therapy for
      PD and other related synucleopathies.

PMID- 29027058
TI  - The Impact of Religiosity on Substance Abuse and Obesity in African Americans.
AB  - Among the African American community, there exist many health disparities which
      warrant greater examination through the practice of social work. The aim of the
      present research was to explore the impact of religiosity on substance abuse and
      obesity among African American populations by employing a systematic review of
      the current body of literature on this subject. While many of the studies
      reviewed found at least a weak relationship between religiosity and obesity, such
      results were not consistent across all materials examined. Among those studies
      that found a correlation between these factors, many demonstrated that
      religiosity had a positive impact on substance abuse and obesity. A discussion of
      the implications of these findings is submitted as a means of illuminating the
      significance of all research findings that were examined. Limitations such as
      more standardized criteria for inclusion of research material are identified and
      discussed. Implications for future research are presented to promote the
      advancement of future efforts in this area research.

PMID- 29027059
TI  - Bacterial and archaeal communities inhabiting mussels, sediment and water in
      Indonesian anchialine lakes.
AB  - Anchialine lakes are a globally rare and unique ecosystem consisting of saline
      lakes surrounded by land and isolated from the surrounding marine environment.
      These lakes host a unique flora and fauna including numerous endemic species.
      Relatively few studies have, however, studied the prokaryote communities present
      in these lakes and compared them with the surrounding 'open water' marine
      environment. In the present study, we used a 16S rRNA gene barcoded
      pyrosequencing approach to examine prokaryote (Bacteria and Archaea) composition
      in three distinct biotopes (sediment, water and the mussel Brachidontes sp.)
      inhabiting four habitats, namely, three marine lakes and the surrounding marine
      environment of Berau, Indonesia. Biotope and habitat proved significant
      predictors of variation in bacterial and archaeal composition and higher taxon
      abundance. Most bacterial sequences belonged to OTUs assigned to the
      Proteobacteria. Compared to sediment and water, mussels had relatively high
      abundances of the classes Mollicutes and Epsilonproteobacteria. Most archaeal
      sequences, in turn, belonged to OTUs assigned to the Crenarchaeota with the
      relative abundance of crenarchaeotes highest in mussel samples. For both Bacteria
      and Archaea, the main variation in composition was between water samples on the
      one hand and sediment and mussel samples on the other. Sediment and mussels also
      shared much more OTUs than either shared with water. Abundant bacterial OTUs in
      mussels were related to organisms previously obtained from corals, oysters and
      the deepsea mussel Bathymodiolus manusensis. Abundant archaeal OTUs in mussels,
      in contrast, were closely related to organisms previously obtained from sediment.

PMID- 29027060
TI  - The Mental Health of Adolescents Residing in Court-Ordered Foster Care: Findings
      from a Population Survey.
AB  - The mental health of a representative sample of 230 adolescents residing in
      foster care in New South Wales, Australia, was estimated in a state-wide
      epidemiological survey from carer-report responses on the Child Behavior
      Checklist (CBCL) and the Assessment Checklist for Adolescents (ACA). Rates of
      CBCL total problems, externalizing and internalizing scores above the borderline
      range cut-points were 49, 44 and 29% respectively, representing a relative risk
      of 3.8, 3.7 and 2.7 respectively in comparison to Australian children at large.
      These rates are 10-14% lower than that previously estimated for pre-adolescent
      Australian children in foster care. Whereas older age is associated with poorer
      mental health among pre-adolescent children in foster care, the present study
      findings suggest that this effect does not extend into adolescence. Around half
      of adolescents residing in foster care have mental health difficulties requiring
      referral to treatment services, including attachment- and trauma-related
      difficulties that are uncommon among clinic-referred children at large.

PMID- 29027061
TI  - Scleral fixated intraocular lens implantation with a modified Z-suture technique.
AB  - PURPOSE: To evaluate visual outcomes and complications in scleral fixated
      intraocular lens (IOL) implantation with the modified Z-suture technique.
      MATERIALS AND METHODS: Thirty-five eyes of 35 patients (20 male, 15 female) were
      included in the study. Patients underwent scleral fixated IOL implantation using
      the modified Z-suture technique and were followed in terms of visual acuity and
      complications. RESULTS: Mean postoperative follow-up time was 12.46 +/- 7.46
      months. Mean best corrected visual acuity was 1.35 +/- 0.91 logMAR preoperatively
      and 0.48 +/- 0.39 logMAR postoperatively, and difference was statistically
      significant (p < 0.001). No suture-related complications were observed during
      follow-up in any of the patients. Slight infero-temporal dislocation of the IOL
      was observed at postoperative 5 months in one patient (2.85%) who experienced
      blunt trauma. It caused no optical disturbance, and repeated surgery was not
      advised. Transient intravitreal hemorrhage was observed in two patients (5.7%)
      who underwent combined scleral fixation and pupilloplasty. DISCUSSION: The
      modified Z-suture technique is simple, fast, and was determined to be safe in
      terms of complications. However, long-term outcomes should be evaluated in larger
      patient groups.

PMID- 29027062
TI  - Congenital ectropion uveae with glaucoma: a case report.
AB  - Congenital ectropion uveae (CEU) is a rare anomaly characterized by ectropion
      uveae, iris hypoplasia, iridotrabecular dysgenesis and glaucoma. The apparent
      ectropion uveae results from the spread of iris pigment epithelium beyond the
      iris ruff and onto the anterior surface of the iris. Conclusion Open-angle
      glaucoma results due to angle dysgenesis, so patients should be carefully
      examined periodically for its early detection.

PMID- 29027063
TI  - Inflammatory myofibroblastic tumors of the breast with simultaneous intracranial,
      lung, and pancreas involvement: ultrasonographic findings and a review of the
      literature.
AB  - We encountered a case of inflammatory myofibroblastic tumor (IMT) of the breast
      with simultaneous intracranial, lung, and pancreas involvement. Here, we present
      the clinical imaging results and report the significance of sonographic findings
      of breast IMT along with a review of the literature. A 16-year-old girl with a
      history of subarachnoidal hemorrhage was admitted to our hospital due to tonic
      clonic seizure. Computed tomography (CT) and magnetic resonance imaging (MRI)
      showed multiple intracranial, lung, and pancreas mass lesions and a solitary mass
      lesion in the right breast. Breast ultrasonography showed a circumscribed oval
      shaped hypoechoic mass with a central hyperechoic region. Power Doppler
      sonography revealed an unusual spiral-shaped flow signal. Breast tumorectomy was
      performed for definitive diagnosis, and pathological analysis indicated IMT. A
      literature review indicated that ultrasonographic findings of IMT of the breast
      are nonspecific, as in other systems or organs. It would be difficult to make a
      diagnosis of IMT of the breast preoperatively due to its rarity and the lack of
      specificity of clinical imaging findings. In addition, it is better to consider
      the possibility of IMT of the breast especially in younger patients without an
      obvious family history of hereditary breast cancer.

PMID- 29027064
TI  - Light scattering measurements in electron-beam sterilized corneas stored in
      recombinant human serum albumin.
AB  - Irradiated corneal tissues have been used for a variety of ophthalmic procedures
      including glaucoma drainage device covers and lamellar grafts. The maintenance of
      corneal clarity is important, as light obstructions resulting from processing or
      long-term storage of irradiated corneas may negatively affect vision and
      postoperative cosmesis. It has been reported that corneal tissues can be
      preserved in human serum albumin (HSA), however, the clarity of corneas after
      long-term storage in HSA has not been well described. Furthermore, the use of
      donor-pooled serum increases the risk for transmission of blood-borne diseases
      and may induce an immune response in the recipient. Here, we examined changes in
      corneal clarity due to electron-beam (e-beam) irradiation and storage in a
      recombinant human serum albumin (rHSA). Dark-field microscopy was employed to
      examine the light scattering effects of fresh and irradiated corneas. Compared to
      measurements taken prior to tissue preparation and e-beam treatment, irradiated
      corneas showed an average 2.6% increase in light scattering (P = 0.002).
      Irradiated corneas stored in rHSA at room-temperature for 20 months showed an
      average increase of 11.6% light scattering compared to fresh corneas (P ? 0.01),
      but did not negatively affect the visualization of printed text, and were deemed
      suitable for transplant use. Therefore, the slight increase in cornea light
      scattering, and resulting reduction in corneal clarity, after e-beam treatment
      and long-term storage in rHSA may not be clinically significant. These results
      suggest that e-beam sterilized corneal grafts may be used as an alternative to
      fresh tissue for certain ophthalmic applications.

PMID- 29027065
TI  - Blood coagulation parameters after intravitreal injection of aflibercept in
      patients with neovascular age-related macular degeneration.
AB  - PURPOSE: The aim of this study was to evaluate the effect of intravitreal
      injection of aflibercept (IVA) on blood coagulation tests in neovascular age
      related macular degeneration (AMD) patients. METHODS: Thirty-four patients with
      neovascular AMD (study group) and 32 healthy individuals (control group) were
      enrolled. Prothrombin time (PT) and activated partial thromboplastin time (aPTT)
      were measured at different times in patients with neovascular AMD. RESULTS: The
      levels of PT and aPTT after IVA were decreased at 1 month after the first
      injection and 1 month after the second injection compared to the baseline
      measurement in the study group. CONCLUSIONS: IVA may cause a decrease in the
      levels of PT and aPTT at 1 month after the first injection and 1 month after the
      second injection although these results are not statistically significant in our
      study.

PMID- 29027066
TI  - White Matter Microstructure of the Human Mirror Neuron System is Related to
      Symptom Severity in Adults with Autism.
AB  - Mirror neuron system (MNS) dysfunctions might underlie deficits in autism
      spectrum disorders (ASD). Diffusion tensor imaging based probabilistic
      tractography was conducted in 15 adult ASD patients and 13 matched, healthy
      controls. Fractional anisotropy (FA) was quantified to assess group differences
      in tract-related white matter microstructure of both the classical MNS route
      (mediating "emulation") and the alternative temporo-frontal route (mediating
      "mimicry"). Multiple linear regression was used to investigate structure-function
      relationships between MNS connections and ASD symptom severity. There were no
      significant group differences in tract-related FA indicating an intact classical
      MNS in ASD. Direct temporo-frontal connections could not be reconstructed
      challengeing the concept of multiple routes for imitation. Tract-related FA of
      right-hemispheric parieto-frontal connections was negatively related to autism
      symptom severity.

PMID- 29027067
TI  - Human heterologous liver cells transiently improve hyperammonemia and ureagenesis
      in individuals with severe urea cycle disorders.
AB  - BACKGROUND: Urea cycle disorders (UCDs) still have a poor prognosis despite
      several therapeutic advancements. As liver transplantation can provide a cure,
      liver cell therapy (LCT) might be a new therapeutic option in these patients.
      METHODS: Twelve patients with severe UCDs were included in this prospective
      clinical trial. Patients received up to six infusions of cryopreserved human
      heterologous liver cells via a surgically placed catheter in the portal vein.
      Portal vein pressure, portal vein flow, and vital signs were monitored
      continuously. Calcineurin inhibitors and steroids were used for
      immunosuppression. In four patients, ureagenesis was determined with stable
      isotopes. Number and severity of hyperammonemic events and side effects of
      immunosuppression were analyzed during an observation period of up to 2 years.
      RESULTS: No study-related mortality was observed. The application catheter
      dislocated in two children. No significant side effects of catheter application
      or cell infusion were noted in the other ten patients. The overall incidence of
      infections did not differ significantly from a historical control group, and no
      specific side effects of immunosuppression were found. Seven patients were
      treated per protocol and could be analyzed for efficacy. Severe metabolic crises
      could be prevented in all of these patients, moderate crises in four of seven.
      Ureagenesis increased after cell infusion in all patients investigated.
      CONCLUSIONS: We found a favorable safety profile with respect to catheter
      placement, intraportal liver cell infusion, and immunosuppression. More than half
      of the children treated per protocol experienced metabolic stabilization and
      could be safely bridged to liver transplantation.

PMID- 29027068
TI  - Array-CGH Analysis in a Cohort of Phenotypically Well-Characterized Individuals
      with "Essential" Autism Spectrum Disorders.
AB  - Copy-number variants (CNVs) are associated with susceptibility to autism spectrum
      disorder (ASD). To detect the presence of CNVs, we conducted an array-comparative
      genomic hybridization (array-CGH) analysis in 133 children with "essential" ASD
      phenotype. Genetic analyses documented that 12 children had causative CNVs (C
      CNVs), 29 children had non-causative CNVs (NC-CNVs) and 92 children without CNVs
      (W-CNVs). Results on clinical evaluation showed no differences in cognitive
      abilities among the three groups, and a higher number of ASD symptoms and of non
      verbal children in the C-CNVs group compared to the W-CNVs and NC-CNVs groups.
      Our results highlighted the importance of the array-CGH analyses and showed that
      the presence of specific CNVs may differentiate clinical outputs in children with
      ASD.

PMID- 29027070
TI  - Assessment of Current Genetic Counselor Practices in Post-Visit Written
      Communications to Patients.
AB  - Providing patients with post-visit written communication (PVWC) is a long
      standing component of genetic counseling. However the depiction of this practice
      in today's clinical landscape is limited. To better describe this practice, we
      surveyed practicing clinical genetic counselors to ask if they send post-visit
      communications to patients and if so, what are the types, the average length, and
      the average time spent writing. They were also asked the perceived purpose of
      providing PVWC, if/how the practice has changed over time, and factors
      influencing the practice. Eighty three percent (233/280) of participants reported
      sending patients PVWC. Of those, 93% sent at least one communication written in
      patient-friendly language. The type of communication varied by specialty.
      Prenatal genetic counselors were less likely to send patient-specific letters and
      hybrid letters (defined as letters with content intended for both a physician and
      a patient) than those in cancer genetics (p = 0.010, p = 0.001, respectively) or
      pediatric genetics (p = 0.001, p = 0.004, respectively). Prenatal genetic
      counselors spent less time on average writing post-visit communications (19.0
      min) relative to those in cancer and pediatric genetics (30.6 min, p = 0.027 and
      37.7 min, p = 0.001, respectively). The most commonly cited purpose for sending
      PVWC was to provide patients a formal account of what happened during the
      appointment. These data suggest PWVC are still regularly sent to patients but the
      practice is variable and is influenced by numerous factors including specialty,
      years of experience, and time constraints.

PMID- 29027069
TI  - Effects of perceived autonomy support and basic need satisfaction on quality of
      life in hemodialysis patients.
AB  - PURPOSE: Despite a growing understanding of health-related quality of life
      (HRQOL) and its determinants in hemodialysis (HD) patients, little is known about
      the effects and interrelationships concerning the perception of autonomy support
      and basic need satisfaction of HD patients on their HRQOL. Based on self
      determination theory (SDT), this study examines whether HD patients' perceived
      autonomy support from health care practitioners (physicians and nurses) relates
      to the satisfaction of HD patients' basic needs and in turn influences their
      HRQOL. METHODS: A questionnaire was administered to 250 Taiwanese HD patients
      recruited from multiclinical centers and regional hospitals in northern Taiwan.
      Structural equation modeling (SEM) analysis was conducted to examine the causal
      relationships between patient perceptions of autonomy support and HRQOL through
      basic need satisfaction. RESULTS: The empirical results of SEM indicated that the
      HD patients' perceived autonomy support increased the satisfaction of their basic
      needs (autonomy, competency, and relatedness), as expected. The higher degree of
      basic need satisfaction led to higher HRQOL, as measured by physical and mental
      component scores. CONCLUSION: Autonomy support from physicians and nurses
      contributes to improving HD patients' HRQOL through basic need satisfaction. This
      indicates that staff caring for patients with severe chronic diseases should
      offer considerable support for patient autonomy.

PMID- 29027071
TI  - The Brain's Reward Response Occurs Even Without Actual Reward!
AB  - What if the brain's response to reward occurs even when there is no reward?
      Wouldn't that be a further concern for people prone to problem gambling and other
      forms of addiction, like those related to eating? Electroencephalography was
      employed to investigate this possibility using probabilistic feedback
      manipulations and measures of known event-related potentials (ERPs) related to
      reward processing. We tested the hypothesis-that reward-based ERPs would occur
      even in the absence of a tangible reward and when manipulations on expectation
      are implicit. The well-known P300 response potential was a key focus, and was
      assessed in non-gambling volunteer undergraduates on a task involving
      experimentally-manipulated probabilities of positive or negative feedback
      comprising three trial types-80, 50, or 20% positive feedback. A feedback
      stimulus (F1) followed a guess response between two possible outcomes (implicit
      win/loss), and then a second feedback stimulus (F2) was presented to confirm an
      alleged 'win' or 'loss' (explicit win/loss). Results revealed that amplitude of
      the P300 in F1-locked data (implicit manipulation) was larger (more positive) on
      average for feedback outcomes that were manipulated to be less likely than
      expected. The effect is pronounced after increased time on task (later trials),
      even though the majority of participants were not explicitly aware of our
      probability manipulations. For the explicit effects in F2-locked data, no
      meaningful or significant effects were observed. These findings point to the
      existence of proposed success-response mechanisms that operate not only
      explicitly but also with implicit manipulations that do not involve any direct
      indication of a win or loss, and are not associated with tangible rewards. Thus,
      there seems to be a non-explicit form of perception (we call 'implicit')
      associated with an internal experience of wins/losses (in the absence of actual
      rewards or losses) that can be measured in associated brain processes. The
      potential significance of these findings is discussed in terms of implications
      for problem gambling.

PMID- 29027073
TI  - Typhlophoros kwenae n. sp. (Nematoda: Ascaridida: Heterocheilidae), a gastric
      parasite from the Nile crocodile Crocodylus niloticus Laurenti (Reptilia:
      Crocodylidae) in South Africa.
AB  - Based on light and scanning electron microscopical observations, Typhlophoros
      kwenae n. sp. (Heterocheilidae), a new nematode parasite, is described from the
      stomach of the Nile crocodile Crocodylus niloticus Laurenti in South Africa. In
      having three lips with well-developed posterior prolongations and prominent
      interlabial longitudinal cuticular ridges, four pairs of precloacal papillae and
      complex spicules divided into handle and broad alate blade in males, as well as
      the position of the vulva near mid-body in females, the specimens conform to the
      generic diagnosis of Typhlophoros von Linstow, 1906. They can, however, be
      distinguished from the two previously described congeners, T. lamellaris von
      Linstow, 1906 and T. spratti Sprent, 1999, by the number of complete interlabial
      ridges, the length of spicules in males and the position of the vulva as well as
      the length of the tail in females. This is the first record of the genus
      Typhlophoros from the Afrotropical Realm.

PMID- 29027072
TI  - Outcomes of acute kidney injury in a nephrology ward.
AB  - Acute kidney injury (AKI) is a global problem which predicts immediate and long
      term adverse outcomes. We evaluated the AKI progression to end-stage renal
      disease, as well as the mortality associated with AKI and the in-hospital
      readmission rate because of a cardiovascular event in AKI patients admitted in a
      nephrology ward. A 5-year retrospective study was set in a nephrology department,
      with a follow-up period of up to 8 years. In a total of 191 patients, mean age
      was 73.83 +/- 12.49 years, and 137 (71.7%) patients had history of chronic kidney
      disease. One hundred and twenty-four (65%) patients needed RRT and two (1%)
      needed surgery. Upon discharge, 107 (56%) patients had recovered the renal
      function, 41 (21.6%) patients had partial recovery, 25 (13%) patients were RRT
      dependent, 16 (8.4%) died, and two (1%) patients had outcomes unknown to us,
      because they were transferred to other hospitals. The median survival time free
      of RRT was 74 months. The median survival time of the followed patients was 34
      months (95% CI 23.3-44.7). The mortality rate in the follow-up period in this
      sample was 18 deaths/100 patients-years, and the incidence of a composite
      cardiovascular endpoint of heart failure, acute coronary syndrome, and stroke was
      6 events/100 patients-years. The mortality rate in the follow-up period was
      higher than usually described for patients outside intensive care unit, probably
      because our patients were old and had many comorbidities.

PMID- 29027074
TI  - Uptake of Radium-223 Dichloride and Early [18F]NaF PET Response Are Driven by
      Baseline [18F]NaF Parameters: a Pilot Study in Castration-Resistant Prostate
      Cancer Patients.
AB  - PURPOSE: The purpose of this study is to identify predictive factors on baseline
      [18F]NaF positron emission tomography (PET)/computed tomography (CT) of early
      response to radium-223 dichloride after 3 cycles of treatment in metastatic
      castration-resistant prostate cancer patients. PROCEDURES: Analysis of 152
      metastases was performed in six consecutive patients who underwent [18F]NaF
      PET/CT at baseline and for early monitoring after 3 cycles of radium-223
      dichloride. All metastases depicted on whole-body [18F]NaF PET/CT were contoured
      and CT (density in Hounsfield units, sclerotic, mixed, or lytic appearance) as
      well as [18F]NaF [maximum standardized uptake value (SUVmax), SUVmean, and lesion
      volume (V18F-NaF)] patterns were recorded. Tumor response was defined as
      percentage change in SUVmax and SUVmean between baseline and post-treatment PET.
      Bone lesions were defined as stable, responsive, or progressive, according to
      thresholds derived from a recent multicentre test-retest study in [18F]NaF
      PET/CT. Total [18F]NaF uptake in metastases, defined as MATV * SUVmean, was
      correlated to uptake of radium-223 on biodistribution scintigraphy performed 7
      days after the first cycle of treatment. RESULTS: Among metastases, 116 involved
      the axial skeleton and 36 the appendicular skeleton. Lesions were sclerotic in
      126 cases and mixed in 26 cases. No lytic lesion was depicted. ROC analysis
      showed that SUVmax and SUVmean were better predictors of lesion response than
      V18F-NaF and density on CT (P < 0.0001 and P = 0.001, respectively). SUVmax and
      SUVmean were predictors of individual tumor response in separate multivariate
      models (P = 0.01 and P = 0.02, respectively). CT pattern (mixed versus sclerotic)
      and lesion density were independent predictors only when assessing response with
      delta SUVmax (P = 0.002 and 0.007, respectively). A good correlation between
      total [18F]NaF uptake within metastases and their relative radium-223 uptake
      assessed by two observers 7 days after treatment (r = 0.72 and 0.77, P < 0.0001)
      was found. CONCLUSIONS: SUVmax and SUVmean on baseline [18F]NaF PET/CT are
      independent predictors of bone lesions' response to 3 cycles of radium-223
      dichloride, supporting the use of NaF to select patients more likely to respond
      to treatment.

PMID- 29027075
TI  - Optimization of non-thermal plasma efficiency in the simultaneous elimination of
      benzene, toluene, ethyl-benzene, and xylene from polluted airstreams using
      response surface methodology.
AB  - Treatment with a non-thermal plasma (NTP) is a new and effective technology
      applied recently for conversion of gases for air pollution control. This research
      was initiated to optimize the efficient application of the NTP process in
      benzene, toluene, ethyl-benzene, and xylene (BTEX) removal. The effects of four
      variables including temperature, initial BTEX concentration, voltage, and flow
      rate on the BTEX elimination efficiency were investigated using response surface
      methodology (RSM). The constructed model was evaluated by analysis of variance
      (ANOVA). The model goodness-of-fit and statistical significance was assessed
      using determination coefficients (R 2 and R 2adj) and the F-test. The results
      revealed that the R 2 proportion was greater than 0.96 for BTEX removal
      efficiency. The statistical analysis demonstrated that the BTEX removal
      efficiency was significantly correlated with the temperature, BTEX concentration,
      voltage, and flow rate. Voltage was the most influential variable affecting the
      dependent variable as it exerted a significant effect (p < 0.0001) on the
      response variable. According to the achieved results, NTP can be applied as a
      progressive, cost-effective, and practical process for treatment of airstreams
      polluted with BTEX in conditions of low residence time and high concentrations of
      pollutants.

PMID- 29027076
TI  - Assessing the stability in dry mycelial fertilizer of Penicillium chrysogenum as
      soil amendment via fluorescence excitation-emission matrix spectra: organic
      matter's transformation and maturity.
AB  - Utilization as dry mycelial fertilizer (DMF) produced from penicillin
      fermentation fungi mycelium (PFFM) with an acid-heating pretreatment is a
      potential way. To study the transformation and stability of water-extractable
      organic matter in DMF-amended soil via fluorescence regional integration (FRI) of
      fluorescence excitation-emission matrix (EEM), a soil experiment in pot was
      carried out. The results showed that residual penicillin (about 32 mg/kg) was
      almost degraded in the first 5 days, indicating that the drug pollution was in
      control. The pH value, DOC, DON, and DOC/DON presented a classical profile, but
      germination index (GI) leveled off about 0.13 till day 13 in DMF-12% treatment
      due to the severe phytotoxicity. The addition of DMF significantly increased the
      soil microbial populations in contrast to the CON treatment. The EEM showed that
      the protein-like and microbial byproduct-like matters vanished on the 25th and
      33rd days, whereas the fulvic-like substances appeared on the 7th day. The humic
      like substances existed in original samples but their content greatly enhanced
      finally. The FRI results showed that P V, n/P III, n reached the highest value of
      1.84 on the 25th day, suggesting that DMF maintained stable in amended soil.
      Because of its consistency with the results of GI and DOC/DON, the EEM-FRI has a
      potential to evaluate the stability of DMF in soil.

PMID- 29027077
TI  - Optimization of Dendritic Cell-Mediated Cytotoxic T-Cell Activation by Tracking
      of Dendritic Cell Migration Using Reporter Gene Imaging.
AB  - PURPOSE: The aim of this study is to optimize the dendritic cell (DC)-mediated T
      cell activation using reporter gene imaging and flow cytometric analysis in
      living mice. PROCEDURES: A murine dendritic cell line (DC2.4) co-expressing
      effluc and Thy1.1 genes were established by transfection with retroviral vectors.
      Thy1.1 positive cells were sorted by magnetic bead separation system
      (DC2.4/effluc). Cell proliferation assay and phenotype analysis to determine the
      effects of gene transduction on the function of dendritic cells between parental
      DC2.4 and DC2.4/effluc were performed. To optimize the DC-mediated immune
      response by cell number or frequency, different cell numbers (5 * 105, 1 * 106,
      and 2 * 106 DC2.4/effluc) or different frequencies of DC2.4/effluc (first,
      second, and third injections) were injected in the right footpad of mice. The
      migration of the DC2.4/effluc into the draining popliteal lymph node of mice was
      monitored by bioluminescence imaging (BLI). Flow cytometric analysis was
      performed with splenocytes to determine the cytotoxic T-cell population after
      injection of DC2.4/effluc. RESULTS: Parental DC2.4 and DC2.4/effluc exhibit no
      significant differences in their proliferation and phenotype. BLI signals were
      observed in the draining popliteal lymph node at day 1 after injection of
      DC2.4/effluc in 1 * 106 and 2 * 106 cells-injected groups. The highest BLI signal
      intensity was detected in 2 * 106 cells-injected mice. On day 11, the BLI signal
      was detected in only 2 * 106 cell-injected group but not in other groups.
      Optimized cell numbers (2 * 106) were injected in three animal groups with a
      different frequency (first, second, and third injection groups). The BLI signal
      was detected at day 1 and maintained until day 7 in the first injection group,
      but there is low signal intensity in the second and the third injection groups.
      Although the expression levels of Thy1.1 gene in the first injection group were
      very high, there reveals no expression of Thy1.1 gene in the second and the third
      injection groups. The number of tumor-specific CD8+ T-cells in the spleen
      significantly increased, as the number of DC injections increases. CONCLUSIONS:
      Successful optimization of DC-mediated cytotoxic T-cell activation in living mice
      using reporter gene imaging and flow cytometric analysis was achieved. The
      optimization of DC-mediated cytotoxic T-cell activation could be applied for the
      future DC-based immunotherapy.

PMID- 29027078
TI  - Dynamic Scheduling for Veterans Health Administration Patients using Geospatial
      Dynamic Overbooking.
AB  - The Veterans Health Administration (VHA) is plagued by abnormally high no-show
      and cancellation rates that reduce the productivity and efficiency of its medical
      outpatient clinics. We address this issue by developing a dynamic scheduling
      system that utilizes mobile computing via geo-location data to estimate the
      likelihood of a patient arriving on time for a scheduled appointment. These
      likelihoods are used to update the clinic's schedule in real time. When a
      patient's arrival probability falls below a given threshold, the patient's
      appointment is canceled. This appointment is immediately reassigned to another
      patient drawn from a pool of patients who are actively seeking an appointment.
      The replacement patients are prioritized using their arrival probability. Real
      world data were not available for this study, so synthetic patient data were
      generated to test the feasibility of the design. The method for predicting the
      arrival probability was verified on a real set of taxicab data. This study
      demonstrates that dynamic scheduling using geo-location data can reduce the
      number of unused appointments with minimal risk of double booking resulting from
      incorrect predictions. We acknowledge that there could be privacy concerns with
      regards to government possession of one's location and offer strategies for
      alleviating these concerns in our conclusion.

PMID- 29027079
TI  - Guinea fowl (Numidia meleagris) production by small-holder farmers in Zimbabwe.
AB  - Guinea fowls are a source of high-value meat and eggs, and the birds are more
      disease resistant than other types of birds. A survey was conducted in ward 23,
      Chipinge district, Zimbabwe, to characterise guinea fowl management practices and
      to identify constraints and potential opportunities for increased guinea fowl
      productivity. Purposive sampling was used to select 84 out of possible 252 guinea
      fowl owners. Data were collected by direct observation on guinea fowl varieties,
      feeding strategies and housing facilities. A semi-structured questionnaire was
      used to collect data on farmer experiences, perceptions and common challenges
      encountered. A chi-squared test was conducted using the IBM SPSS Statistical
      Package for Social Sciences (SPSS) version 21. The study revealed that famers
      keep guinea fowls under free-range management. The average production indices
      were flock size 18 +/- 12, egg production 89 +/- 50, hatchability 63.8% and keet
      survival rate of 75%. Approximately 42.9% of the farmers provide supplementary
      feed albeit not systematically. There was a significant association between
      provision of supplementary feed and keet survival rate (chi 2 = 21.600, df = 2, P
      < 0.016) as well as provision of housing and flock size (chi 2 = 38.508, df = 3,
      P < 0.018). The housing provided was substandard. Major challenges faced by
      farmers were predation, low hatchability and lack of access to profitable
      markets. The provision of supplements and better housing for birds could improve
      guinea fowl productivity.

PMID- 29027080
TI  - Different expression systems resulted in varied binding properties of anti
      paclitaxel single-chain variable fragment antibody clone 1C2.
AB  - The binding properties of recombinant antibody fragments, such as affinity and
      specificity, determine their usefulness for therapeutic and analytical
      applications. Anti-paclitaxel single-chain variable fragment clone 1C2 (anti-PT
      scFv1C2) was expressed using Escherichia coli cell and Bombyx mori larvae
      expression systems. The binding characteristics of the scFvs were evaluated using
      indirect competitive ELISA. The linear range of binding between anti-PT scFv1C2
      and paclitaxel was significantly different between the anti-PT scFv1C2s derived
      from E. coli (1.056-5.700 MUg/ml) and B. mori (7.813-1000 ng/ml), which indicated
      that different expression systems resulted in different sensitivities for
      paclitaxel determination. In addition, the binding specificity of anti-PT scFv1C2
      varied between expression systems. This finding implied that the expression
      system significantly affects the binding properties of recombinant antibodies,
      especially antibodies against low-molecular-weight targets.

PMID- 29027081
TI  - Fate of triclocarban in agricultural soils after biosolid applications.
AB  - Triclocarban [N-(4-chlorophenyl)-N-(3,4-dichlorophenyl) urea] (TCC) is an
      antimicrobial agent utilized in a variety of consumer products. It is commonly
      released into domestic wastewaters and upon treatment, it is known to accumulate
      in biosolids. This study examines the occurrence of TCC in biosolids and its long
      term fate in biosolid-treated soils. TCC levels in the biosolids from a large
      waste water treatment plant (WWTP) over 2 years showed little variability at
      18,800 +/- 700 ng g-1 dry wt. (mean +/- SEM). Surface soil samples (top 10 cm)
      were collected from 26 commercial farms located in northern VA, US that had
      received biosolid applications from the WWTP. Samples were grouped as farms
      receiving no biosolids, farms with a single biosolid application, and those
      receiving multiple biosolid applications from 1992 to 2006. Our results
      illustrate that TCC soil residues remained years after biosolid application. The
      two most important parameters controlling TCC topsoil concentrations were the
      biosolid application rate and the period since the last application. No TCC
      removal was observed in farms where the time since biosolid application was
      between 7 and 9 months. TCC concentration analyzed 7 and 8 years after biosolid
      applications were 45.8 +/- 6.1 and 72.4 +/- 15.3 ng g-1 dry wt., respectively,
      showing its persistence in soils and build-up upon multiple biosolid
      applications. A soil TCC half-life of 287.5 +/- 45.5 days was estimated.

PMID- 29027082
TI  - Factors associating with the presence of residual thrombosis after 3-month
      treatment of acute pulmonary embolism.
AB  - The present study aimed to investigate the factors associating with the presence
      of residual thrombosis in patients with acute pulmonary embolism (APE) after at
      least 3-month anticoagulant therapy. Demographic and clinical data of 180 cases
      in the affiliated hospital of Qingdao University from January 2005 to June 2015
      were retrospectively analyzed. APE in all patients were confirmed by computed
      tomography pulmonary angiography (CTPA). Patients were then detected for the
      presence of residual thrombosis according to a second CTPA. After appropriate
      comparison test, multivariate logistic regression analysis was performed to
      identify predictors for residual thrombosis. Among 180 patients, complete
      clearance of thrombosis occurred in 115 (63.9%) patients. Residual thrombosis
      remained in 65 (36.1%) patients. The independent factors associating with
      residual thrombosis include unprovoked APE (OR 0.231, 95% CI 0.062-0.861) and
      fibrinogen level in acute phase (OR 1.958, 95% CI 1.282-2.911). Furthermore,
      these two variables were both associated with the presence of residual thrombosis
      in patients receiving different parenteral anticoagulants (unfractionated heparin
      or low-molecular-weight heparin). Pulmonary thrombosis in some patients with APE
      are not completely dissolved after at least 3-month treatment. Additionally,
      unprovoked APE is positive predictor of decreased residual thrombosis and
      fibrinogen level in acute phase is a risk factor of the presence of residual
      thrombosis.

PMID- 29027083
TI  - Objective and subjective results following implantation of the FineVision
      trifocal intraocular lens in Mexican patients.
AB  - PURPOSE: To evaluate objective and subjective results after bilateral
      implantation of a diffractive trifocal intraocular lens (IOL) in a Mexican
      population. METHODS: Prospective, interventional case series involved 15 cataract
      surgery patients who underwent bilateral implantation of the trifocal Micro F
      lens FineVision IOL (PhysIOL, Liege, Belgium). Objective analysis involved
      assessment of monocular uncorrected distance (UDVA), near (UNVA) at 30 and 40 cm,
      and intermediate visual acuity (UIVA) at 50, 60, and 70 cm, preoperatively, and
      at postoperative months 1, 3, and 6. Higher-order aberrations were assessed via
      aberrometry. Contrast sensitivity was determined via modulation transfer
      function. Subjective outcomes were assessed using the National Eye Institute
      Visual Functioning Questionnaire-25 (VFQ-25). RESULTS: At postoperative month 6,
      mean monocular UDVA was 0.06 +/- 0.11 logMAR, and UNVA was 0.03 +/- 0.04 logMAR
      at 30 cm and 0.05 +/- 0.08 logMAR at 40 cm. Mean UIVA at 50, 60, and 70 cm was
      0.12 +/- 0.06, 0.13 +/- 0.08, and 0.04 +/- 0.08 logMAR, respectively. Spherical
      equivalent at postoperative month 3 was 0.23 +/- 0.4 diopters (D). Aberrometry
      revealed a mean RMS of 0.18 microm and PSF of 0.19 (Strehl ratio). VFQ-25
      questionnaire results showed a mean score of 93.64 +/- 4.19 points (maximum 100
      points). Vision during distance and near activities was reported as "excellent."
      Adverse events were reported as occurring "never to occasionally." CONCLUSION:
      Implantation of a diffractive trifocal IOL in a Mexican population appears safe
      and effective, both objectively and subjectively. Good uncorrected visual acuity
      outcomes were achieved at far, near, and intermediate distances. Overall patient
      satisfaction was excellent.

PMID- 29027085
TI  - Two new cytotoxic stilbenoid dimers isolated from Cajanus cajan.
AB  - Two new stilbenoid dimers, cajanstilbenoids A (1) and B (2), were isolated from
      the leaves of Cajanus cajan. Planar structures of these compounds were verified
      by NMR (1D and 2D) and high-resolution electrospray ionization mass spectroscopy
      (HR-ESI-MS). Absolute configurations were assigned by comparing experimental and
      calculated electronic CD values. The cytotoxicity of 1 and 2 against human
      hepatoma (HepG2), human breast adenocarcinoma (MCF-7), and human lung cancer
      (A549) cells were evaluated in vitro. Compound 1 showed strong cytotoxicity
      against all the tested cell lines (IC50 values: 2.14-2.56 uM), whereas compound 2
      showed strong toxicity only against HepG2 (IC50 value: 5.99 uM) and A549 cells
      (IC50 value: 6.18 uM).

PMID- 29027084
TI  - Association of light-to-moderate alcohol drinking in pregnancy with preterm birth
      and birth weight: elucidating bias by pooling data from nine European cohorts.
AB  - Women who drink light-to-moderately during pregnancy have been observed to have
      lower risk of unfavourable pregnancy outcomes than abstainers. This has been
      suggested to be a result of bias. In a pooled sample, including 193 747 live-born
      singletons from nine European cohorts, we examined the associations between light
      to-moderate drinking and preterm birth, birth weight, and small-for-gestational
      age in term born children (term SGA). To address potential sources of bias, we
      compared the associations from the total sample with a sub-sample restricted to
      first-time pregnant women who conceived within six months of trying, and examined
      whether the associations varied across calendar time. In the total sample,
      drinking up to around six drinks per week as compared to abstaining was
      associated with lower risk of preterm birth, whereas no significant associations
      were found for birth weight or term SGA. Drinking six or more drinks per week was
      associated with lower birth weight and higher risk of term SGA, but no increased
      risk of preterm birth. The analyses restricted to women without reproductive
      experience revealed similar results. Before 2000 approximately half of pregnant
      women drank alcohol. This decreased to 39% in 2000-2004, and 14% in 2005-2011.
      Before 2000, every additional drink was associated with reduced mean birth
      weight, whereas in 2005-2011, the mean birth weight increased with increasing
      intake. The period-specific associations between low-to-moderate drinking and
      birth weight, which also were observed for term SGA, are indicative of bias. It
      is impossible to distinguish if the bias is attributable to unmeasured
      confounding, which change over time or cohort heterogeneity.

PMID- 29027086
TI  - The association between somatic and psychological discomfort and health-related
      quality of life according to the elderly and non-elderly.
AB  - PURPOSE: Symptoms and discomfort are common complaints in primary care settings.
      It has been postulated that the physical symptoms are informative index in
      estimating Health-related quality of life (HRQOL). Thus, we conducted a community
      based cross-sectional study to assess the relationship between somatic and
      psychological discomfort and HRQOL in elderly and non-elderly people. METHODS: A
      total of 2467 participants were recruited in 2013 from a population of 17,066
      rural residents aged 20 or older. Information on demographic characteristics,
      somatic and psychological discomfort symptoms, and HRQOL was collected. Two
      months after the baseline survey, we conducted a repeated survey to assess
      changes in the discomfort symptoms and HRQOL. We evaluated associations of the
      discomfort symptoms with HRQOL using multiple linear regression and mixed model.
      RESULTS: EuroQol-Visual Analogue Scale (EQ-VAS), index of HRQOL, was correlated
      with fatigue, pain, sleep disturbances, indigestion, and anxiety/depression,
      after adjusting for covariates. However, the factors most significantly
      associated with EQ-VAS differed between the elderly and non-elderly. Pain was the
      most important factor contributing to EQ-VAS in the elderly, whereas depression
      and anxiety were the predominant factors in the non-elderly. These relationships
      were replicated in the repeated measurements to assess the change of symptoms and
      change of EQ-VAS. CONCLUSION: Our study suggests that somatic and psychological
      discomfort symptoms are associated with HRQOL. The main factors related to HRQOL
      vary according to age and large prospective studies and clinical trials are
      needed to clarify the association between specific symptoms and HRQOL according
      to the age.

PMID- 29027087
TI  - The effect of using a dielectric matching medium in focused microwave radiometry:
      an anatomically detailed head model study.
AB  - Microwave radiometry is a passive technique used to measure in-depth temperature
      distributions inside the human body, potentially useful in clinical applications.
      Experimental data imply that it may provide the capability of detecting in-depth
      local variations of temperature and/or conductivity of excitable tissues at
      microwave frequencies. Specifically, microwave radiometry may allow the real-time
      monitoring of brain temperature and/or conductivity changes, associated with
      local brain activation. In this paper, recent results of our ongoing research
      regarding the capabilities of focused microwave radiometry for brain intracranial
      applications are presented. Electromagnetic and thermal simulation analysis was
      performed using an anatomically detailed head model and a dielectric cap as
      matching medium placed around it, in order to improve the sensitivity and the
      focusing attributes of the system. The theoretical results were compared to
      experimental data elicited while exploring that the sensing depth and spatial
      resolution of the proposed imaging method at 2.1 GHz areas located 3 cm deep
      inside the brain can be measured, while at 2.5 GHz, the sensing area is confined
      specifically to the area of interest. The results exhibit the system's potential
      as a complementary brain imaging tool for multifrequency in-depth passive
      monitoring which could be clinically useful for therapeutic, diagnostic, and
      research applications.

PMID- 29027088
TI  - Redescription of Philometra filiformis (Stossich, 1896) (Nematoda:
      Philometridae), a gonad-infecting parasite of the common pandora Pagellus
      erythrinus (Linnaeus) (Sparidae) in the Mediterranean Sea, including new
      taxonomic features revealed by SEM.
AB  - The insufficiently known nematode species Philometra filiformis (Stossich, 1896)
      (Philometridae) is redescribed based on light and scanning electron microscopical
      (SEM) examinations of specimens collected from the ovaries of the type-host, the
      common pandora Pagellus erythrinus (Linnaeus) (Perciformes, Sparidae), from off
      the Mediterranean coast of Tunisia. The male of this species was studied with SEM
      for the first time, which revealed some new, taxonomically important
      morphological features. The male posterior end has a caudal mound consisting of
      two lateral parts widely separated dorsally from each other, four pairs of small
      adanal papillae, a pair of large but moderately developed papillae located
      posterior to the cloacal aperture and a pair of small phasmids. The distal end of
      the gubernaculum is unique among all but one gonad-infecting species of
      Philometra Costa, 1845 by the chevron-shaped dorsal lamellar structures forming a
      median longitudinal range. Philometra filiformis is for the first time reported
      from Tunisian coastal waters, being the seventh philometrid species so far
      recorded from marine fishes off Tunisia.

PMID- 29027089
TI  - A decade of a thrips invasion in China: lessons learned.
AB  - The Western flower thrips, Frankliniella occidentalis Pergande (Thysanoptera:
      Thripidae) is an invasive polyphagous pest with an expanding global range that
      damages a wide variety of crops. F. occidentalis was first reported in China from
      Yunnan province during 2000, and has rapidly expanded its range since then. It is
      currently distributed across at least 10 provinces in China and has become a
      particularly devastating pest, causing substantial damage and economic losses. At
      present, the still heavy reliance on frequent use of insecticides for control of
      F. occidentalis, has lead to a series of ecological problems stemming from
      insecticide resistance, interspecific displacement and non-target effects. Thus,
      integrated pest management (IPM) programmes, multiple complementary tactics,
      including preventive tactics, biological controls, and judicious use of
      insecticides will likely provide a viable IPM strategy for control of F.
      occidentalis in the near future. This review provides an overview for information
      gained during the 10+ years since the invasion of F. occidentalis into China,
      reviews lessons that have been learned enhancing our overall understanding of the
      biology and ecology of F. occidentalis and discusses IPM practices relative to
      this widespread invasive insect pest.

PMID- 29027090
TI  - Morphological and molecular data for a new species of Pomphorhynchus Monticelli,
      1905 (Acanthocephala: Pomphorhynchidae) in the Mexican redhorse Moxostoma
      austrinum Bean (Cypriniformes: Catostomidae) in central Mexico.
AB  - Pomphorhynchus purhepechus n. sp. is described from the intestine of the Mexican
      redhorse Moxostoma austrinum Bean (Catostomidae) in central Mexico. The new
      species can be distinguished from the other seven described species of
      Pomphorhynchus Monticelli, 1905 in the Americas by a subspherical proboscis and
      14 longitudinal rows with 16-18 hooks each; the third and the fourth row of hooks
      are alternately longest. Sequences of the mitochondrial cytochrome c oxidase
      subunit 1 (cox1) gene and the large subunit (LSU) rDNA (including the domains D2
      D3) were used to corroborate the morphological distinction between the new
      species and Pomphorhynchus bulbocolli Linkins in Van Cleave, 1919, a species
      widely distributed in several freshwater fish species across Canada, USA, and
      Mexico. The genetic divergence estimated between the new species and the isolates
      of P. bulbocolli ranged between 13 and 14% for cox1, and between 0.6 and 0.8% for
      LSU. Maximum likelihood and Bayesian inference analyses of each dataset showed
      that the isolates of P. bulbocolli parasitising freshwater fishes from three
      families, the Catostomidae, Cyprinidae and Centrarchidae, represent a separate
      lineage, and that the acanthocephalans collected from two localities in central
      Mexico comprise an independent lineage. In addition, our analysis of the genetic
      variation of P. bulbocolli demonstrates that individuals of this acanthocephalan
      from different host species are conspecific. Finally, the distribution, host
      association, and phylogenetic relationship of the new species, when placed in the
      context of the region's geological history, suggest that both host and parasite
      underwent speciation after their ancestors became isolated in Central Mexico.

PMID- 29027091
TI  - Walnut supplementation reverses the scopolamine-induced memory impairment by
      restoration of cholinergic function via mitigating oxidative stress in rats: a
      potential therapeutic intervention for age related neurodegenerative disorders.
AB  - The brain is highly susceptible to the damaging effects of oxidative reactive
      species. The free radicals which are produced as a consequence of aerobic
      respiration can cause cumulative oxygen damage which may lead to age-related
      neurodegeneration. Scopolamine, the anti-muscarinic agent, induces amnesia and
      oxidative stress similar to that observed in the older age. Studies suggest that
      antioxidants derived from plant products may provide protection against oxidative
      stress. Therefore, the present study was designed to investigate the attenuation
      of scopolamine-induced memory impairment and oxidative stress by walnut
      supplementation in rats. Rats in test group were administrated with walnut
      suspension (400 mg/kg/day) for four weeks. Both control and walnut-treated rats
      were then divided into saline and scopolamine-treated groups. Rats in the
      scopolamine group were injected with scopolamine (0.5 mg/kg dissolved in saline)
      five minutes before the start of each memory test. Memory was assessed by
      elevated plus maze (EPM), Morris water maze (MWM), and novel object recognition
      task (NOR) followed by estimation of regional acetylcholine levels and
      acetylcholinesterase activity. In the next phase, brain oxidative status was
      determined by assaying lipid peroxidation, and measuring superoxide dismutase
      (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Results showed
      that scopolamine-treatment impaired memory function, caused cholinergic
      dysfunction, and induced oxidative stress in rats compared to that saline-treated
      controls. These impairments were significantly restored by pre-administration of
      walnut. This study demonstrates that antioxidant properties of walnut may provide
      augmented effects on cholinergic function by reducing oxidative stress and thus
      improving memory performance.

PMID- 29027092
TI  - Toxic effects of oxytetracycline and copper, separately or combined, on soil
      microbial biomasses.
AB  - The production of commercial livestock and poultry often involves using with
      antibiotics and feed additives, such as oxytetracycline (OTC) and copper (Cu).
      These are often excreted into the soil by animal feces; hence, combined
      pollutants may contaminate the soil. To evaluate single and combined toxic
      effects of OTC and Cu on the soil ecology, changes in quantities of bacteria,
      fungi, and actinomycetes in the soil were studied over a 28-d incubation period
      by a plate count method, microbes numbers counted on days 7, 14, 21, and 28.
      Abundances of ammonia monooxygenase (amoA) gene expression by ammonia-oxidizing
      bacteria (AOB) and ammonia-oxidizing archaea (AOA) in soil samples also were
      tested by real-time polymerase chain reactions (RT-PCRs) on day 21. The results
      revealed that the numbers of bacteria, fungi and actinomycetes and amoA genes
      copies of AOA and AOB were reduced seriously by exposure to Cu (1.60 mmol/kg).
      Similarly, the combined pollution treatments (mole ratios of OTC: Cu was 1:2,
      1:8, and 1:32) also had inhibitory effect on bacteria, fungi, and actinomycetes
      numbers and amoA gene copies of AOA and AOB; the inhibitory rate was on obvious
      growth trend with the increasing mole ratios. Effects from single OTC pollution
      were found on bacteria (days 7 and 14), fungi (days 7, 14, 21, and 28), and AOA
      amoA gene copies (day 21), with promotion at a low concentration (0.05 mmol/kg)
      and suppression at higher concentrations (0.2 and 0.8 mmol/kg). Also, numbers of
      bacteria, fungi, and actinomycetes decreased with longer culture times. Combining
      OTC and Cu led to a higher inhibition of soil microbes than when either chemical
      was used alone. However, there was no significant relationship between single and
      combined toxic chemicals because of their complicated interactions, either
      antagonistic or synergistic. The results also indicated the sensitivity of
      bacteria, fungi, actinomycetes on toxic chemicals existed difference and that the
      AOA were more tolerant than the AOB to these chemicals.

PMID- 29027093
TI  - Long-Term Prognostic Value of Coronary Computed Tomography Angiography.
AB  - OPINION STATEMENT: Coronary CT angiography (CTA) is a highly accurate test for
      the diagnosis of coronary artery disease (CAD), with its use guided by numerous
      contemporary appropriate use criteria and clinical guidelines. Unique among non
      invasive tests for CAD, coronary CTA provides direct visualization of coronary
      atherosclerosis for the assessment of angiographic stenosis, as well as validated
      measures of plaque vulnerability. Long-term studies now clearly demonstrate that
      the absence of CAD on coronary CTA identifies a patient that is at very low risk
      for future cardiovascular events. Conversely, the presence, location, and
      severity of CAD as measured on coronary CTA provide powerful prognostic
      information that is superior to traditional risk factors and other clinical
      variables. Observational studies and data obtained from clinical trials suggest
      that the anatomic information derived from coronary CTA significantly increases
      the utilization of statins and aspirin. Furthermore, these changes are associated
      with reductions in the risk for mortality, revascularizations, and incident
      myocardial infarctions among subjects with coronary atherosclerosis. As a result,
      current societal consensus statements have attempted to standardize coronary CTA
      reporting, to include incorporation of vulnerable plaque features and
      recommendations on the use of preventive therapies, such as statins, so to more
      consistently link important prognostic findings on coronary CTA to appropriate
      preventive and therapeutic interventions. Automated measures of total coronary
      plaque volume, machine learning, and CT-derived fractional flow reserve may
      further refine the prognostic accuracy of coronary CTA. Herein, we summarize
      recently published literature that reports the long-term (>= 5 years of follow
      up) prognostic usefulness of coronary CTA.

PMID- 29027094
TI  - Multimodal Functional Neuroimaging by Simultaneous BOLD fMRI and Fiber-Optic
      Calcium Recordings and Optogenetic Control.
AB  - Recent developments of optogenetic tools and fluorescence-based calcium recording
      techniques enable the manipulation and monitoring of neural circuits on a
      cellular level. Non-invasive imaging of brain networks, however, requires the
      application of methods such as blood oxygen level-dependent (BOLD) functional
      magnetic resonance imaging (fMRI), which is commonly used for functional
      neuroimaging. While BOLD fMRI provides brain-wide non-invasive reading of the
      hemodynamic response, it is only an indirect measure of neural activity. Direct
      observation of neural responses requires electrophysiological or optical methods.
      The latter can be combined with optogenetic control of neuronal circuits and are
      MRI compatible. Yet, simultaneous optical recordings are still limited to fiber
      optic-based approaches. Here, we review the integration of optical recordings and
      optogenetic manipulation into fMRI experiments. As a practical example, we
      describe how BOLD fMRI in a 9.4-T small animal MR scanner can be combined with in
      vivo fiber-optic calcium recordings and optogenetic control in a multimodal
      setup. We present simultaneous BOLD fMRI and calcium recordings under optogenetic
      control in rat. We outline details about MR coil configuration, choice, and usage
      of opsins and chemically and genetically encoded calcium sensors, fiber
      implantation, appropriate light power for stimulation, and calcium signal
      detection, to provide a glimpse into challenges and opportunities of this
      multimodal molecular neuroimaging approach.

PMID- 29027095
TI  - Multimodality Imaging of Pericardial Diseases.
AB  - OPINION STATEMENT: Pericardial diseases have changed their epidemiology in the
      past few years. With the aging population and decreasing incidence of
      communicable diseases, the causes of pericardial diseases have significantly
      changed from infectious and malignant to postradiation and cardiac surgery
      causes. Despite that, pericardial diseases remain difficult to diagnose. The
      accurate and timely diagnosis of these diseases is essential to avoid the late
      sequela of pericardial constriction and pericardial cirrhosis. Echocardiography
      remains the first test of choice for the assessment of patients with suspected
      pericardial diseases. Most patients with acute pericarditis have a self-limiting
      course and do not need further imaging. However, in the era of multimodality
      imaging, other modalities, namely, computed tomography (CT) and magnetic
      resonance imaging (CMR), are often utilized in complex cases. These two
      modalities provide a wide-open view of the pericardium and adjacent structures.
      They have high resolution to assess pericardial calcification, a hallmark of many
      diseases especially tuberculous constrictive pericarditis. CMR is also unique in
      its ability to assess pericardial late gadolinium enhancement (LGE) and edema.
      These have been recently suggested to be very important in the progression from
      acute pericarditis to constrictive pericarditis. In addition, they provide
      prognostic value to assess which patients are at high risk of developing heart
      failure and resource utilization. Thus, in the current era, patients with
      suspected complex pericardial diseases will need a multimodality approach rather
      than a single modality approach.

PMID- 29027096
TI  - New Innovations in Drug-Eluting Stents for Peripheral Arterial Disease.
AB  - PURPOSE OF REVIEW: The purpose of this paper was to provide a review of the
      burden of peripheral arterial disease; to examine older therapies and their
      limitations; and especially to highlight new treatment innovations as well as the
      data supporting their use. RECENT FINDINGS: Building on the success of paclitaxel
      in the prevention of restenosis in the peripheral circulation, the newest
      generation drug-eluting stent is presented, which combines paclitaxel with a
      polymer-allowing the drug to be eluted slowly over 12 months. The positive
      results of the pilot MAJESTIC study led to the ongoing IMPERIAL trial. Limited
      data of bioresorbable scaffolds in above and below-the-knee applications are also
      reviewed. Endovascular therapy of peripheral arterial disease has had many
      advances in the preceding two decades. However, drug-eluting stent technology has
      had the greatest impact to date and holds great promise for the future.

PMID- 29027097
TI  - High number of newly initiated direct oral anticoagulant users switch to
      alternate anticoagulant therapy.
AB  - Real-world evidence focusing on medication switching patterns amongst direct oral
      anticoagulant (DOACs) has not been well studied. The objective of this study is
      to evaluate patterns of prescription switching in non-valvular atrial
      fibrillation (NVAF) patients initiated on a DOAC and previously naive to
      anticoagulation (AC) therapy. Data was obtained from Truven Health MarketScan(r)
      Commercial and Medicare Supplemental database (2009-2013). AC naive (those
      without prior anticoagulant use) NVAF patients initiated on a DOAC, with 6 months
      of continuous health plan enrollment before and after treatment initiation and
      maintained on continuous therapy for a minimum of 6 months were included. Of
      34,022 AC naive NVAF patients initiating a DOAC, 6613 (19.4%) patients switched
      from an index DOAC prescription to an alternate anticoagulant and 27,409 (80.6%)
      remained on the DOAC [age: 68.5 +/- 11.7 vs. 67.1 +/- 12.7 years, p < 0.001;
      males: 3781 (57.2%) vs. 17,160 (62.6%), p < 0.001]. Amongst those that switched
      medication, 3196 (48.3%) did so within the first 6 months of therapy. Overall,
      2945 (44.5%) patients switched to warfarin, 2912 (44.0%) switched to another DOAC
      and 756 (11.4%) switched to an injectable anticoagulant. The highest proportion
      of patients switched from dabigatran to warfarin (N = 2320; 42.5%) or rivaroxaban
      (N = 2252; 41.3%). The median time to switch from the index DOAC to another DOAC
      was 309.5 days versus 118.0 days (p < 0.001) to switch to warfarin. In NVAF
      patients newly initiated on DOAC therapy, one in five patients switch to an
      alternate anticoagulant and one of every two patients do so within the first 6
      months of therapy. Switching from an initial DOAC prescription to traditional
      anticoagulants occurs as frequently as switching to an alternate DOAC.

PMID- 29027098
TI  - Voluntary feed intake and growth performance of slow-growing pigs fed on
      increasing levels of ensiled potato hash meal.
AB  - The objective of the study was to determine voluntary feed intake and growth
      performance of Windsnyer pigs fed on increasing levels of potato hash silage
      meal. Thirty-six growing Windsnyer pigs (19 kg +/- 5.59) (mean +/- standard
      deviation (SD)) were individually and randomly assigned to six experimental diets
      containing 0, 80, 160, 240, 320 and 400 g/kg DM of potato hash silage. Diets
      containing the potato hash silage were formulated using diet dilution method from
      0 g/kg and 400 g/kg. Six pigs were fed on each diet ad libitum for 6 weeks.
      Average daily feed intake (ADFI), average daily gain (ADG), gain to feed (G/F)
      ratio, scaled feed intake (SFI) and scaled average daily gain (SADG) were
      measured weekly. Increasing levels of potato hash silage caused a decrease (P <
      0.05) in ADG, G/F ratio and SADG. The ADFI interacted significantly (P < 0.05)
      with the inclusion level of potato hash silage and week of feeding. Pigs fed on
      240 g/kg potato hash silage had greater ADFI in the second, third and fourth week
      of feeding. There was a quadratic increase (P < 0.05) in ADFI. There was a linear
      decrease (P < 0.05) in ADG and G/F ratio and SADG as the potato hash silage level
      increased. Using piecewise regression, potato hash silage can be included up to
      240 g/kg DM in Windsnyer pigs without undermining growth performance.

PMID- 29027099
TI  - Risk factor of bronchopleural fistula after general thoracic surgery: review
      article.
AB  - OBJECTIVE: The aim of this article was to clarify recent risk factors for the
      early bronchopleural fistula after anatomical lung resection. METHODS: Reports on
      early bronchopleural fistula after anatomical lung resection in adults, including
      information on risk factors, published between 2006 and 2016 were reviewed and
      our institutional data were evaluated. The early period was defined as within 30
      days from surgery or as described early in the manuscript. RESULTS: A total of
      seven retrospective observational articles were selected. Four articles
      investigated lobectomy and pneumonectomy, while the other three articles
      investigated only pneumonectomy. The surgical procedure, preoperative therapy,
      complications after surgery, right side, patient age, past history, and tumor
      residuals were mentioned as risk factors of bronchopleural fistula. Our data
      concluded that neoadjuvant therapy and a right lower lobe location were risk
      factors after a lobectomy, while a right side and complete pneumonectomy were
      risk factors after a pneumonectomy. CONCLUSIONS: Although recent studies have
      reached nearly the same conclusions as older reports, continuous research of
      potential risk factor is needed as therapeutic procedures continue to evolve.

PMID- 29027100
TI  - CORR Insights(r): Does the Risk of Rerevision Vary Between Porous Tantalum Cups
      and Other Cementless Designs After Revision Hip Arthroplasty?

PMID- 29027101
TI  - Reply to the Letter to the Editor: Editorial: Do Orthopaedic Surgeons Belong on
      the Sidelines at American Football Games?

PMID- 29027103
TI  - Letter to the Editor: Editorial: Do Orthopaedic Surgeons Belong on the Sidelines
      at American Football Games?

PMID- 29027102
TI  - Current Status of the Female Athlete Triad: Update and Future Directions.
AB  - PURPOSE OF REVIEW: This review provides an update on the primary clinical
      sequelae of the Female Athlete Triad. RECENT FINDINGS: Scientific advancements
      have contributed to improve understanding of Triad-related conditions, including
      leptin's role as a potential neuroendocrine link between energy status and
      reproductive function. Use of finite element analysis of HRpQCT imaging has
      provided a more accurate assessment of bone geometry and bone strength and may be
      clinically relevant. New perspectives aimed at developing and implementing a
      multi-disciplinary, personalized approach in the prevention and early treatment
      of triad-related symptoms are provided. The Female Athlete Triad is a multi
      dimensional condition that affects active women across the lifespan. Energy
      availability impacts reproductive function and bone with implications for health
      and performance. Understanding the contributions of each individual component as
      well as their interconnected effects is necessary for progression and expansion
      of the Triad literature.

PMID- 29027104
TI  - Cloning, Expression, and Production of Xylo-Oligosaccharides by Using a Newly
      Screened Xylanase Isolated from Bovine Rumen.

PMID- 29027105
TI  - Post-mortem human cadaver scavenging by marine crustaceans (Isopoda: Cirolanidae)
      in tropical waters.
AB  - Animal feeding, both ante- and post-mortem, in freshwater and marine
      environments, has become topical recently. This report documents post-mortem
      scavenging by two identified species of marine crustaceans (Crustacea: Isopoda:
      Cirolanidae) on a human cadaver from the vicinity of Darwin, Northern Territory,
      Australia.

PMID- 29027106
TI  - Fas- and Mitochondria-Mediated Signaling Pathway Involved in Osteoblast Apoptosis
      Induced by AlCl3.
AB  - Aluminum (Al) is known to induce apoptosis of osteoblasts (OBs). However, the
      mechanism is not yet established. To investigate the apoptotic mechanism of OBs
      induced by aluminum trichloride (AlCl3), the primary OBs from the craniums of
      fetal Wistar rats were exposed to 0 mg/mL (control group, CG), 0.06 mg/mL (low
      dose group, LG), 0.12 mg/mL (mid-dose group, MG), and 0.24 mg/mL (high-dose
      group, HG) AlCl3 for 24 h, respectively. We observed that AlCl3 induced OB
      apoptosis with the appearance of apoptotic morphology and increase of apoptosis
      rate. Additionally, AlCl3 treatment activated mitochondrial-mediated signaling
      pathway, accompanied by mitochondrial membrane potential (DeltaPsim)
      depolarization, release of cytochrome c from the mitochondria to the cytoplasm,
      as well as survival signal-related factor caspase-9 and caspase-3 activation.
      AlCl3 exposure also activated Fas/Fas ligand signaling pathway, presented as Fas,
      Fas ligand, and Fas-associated death domain expression enhancement and caspase-8
      activation, as well as the hydrolysis of Bid to truncated Bid, suggesting that
      the Fas-mediated signaling pathway might aggravate mitochondria-mediated OB
      apoptosis through hydrolyzing Bid. Furthermore, AlCl3 exposure inhibited Bcl-2
      protein expression and increased the expressions of Bax, Bak, and Bim in varying
      degrees. These results indicated that AlCl3 exposure induced OB apoptosis through
      activating Fas- and mitochondria-mediated signaling pathway and disrupted B-cell
      lymphoma-2 family proteins.

PMID- 29027107
TI  - Viral factors for HBV mother-to-child transmission.
AB  - Chronic hepatitis B virus (HBV) remains a leading cause of cirrhosis and
      hepatocellular carcinoma worldwide. Because chronic hepatitis B infection is
      rarely eradicated, preventing mother-to-child transmission (MTCT) is the most
      effective strategy to eliminate HBV globally. Although immunoprophylaxis strategy
      is widely available and effective for infants born to mothers with chronic
      hepatitis B infection, postnatal immunoprophylaxis fails in approximately 5-10 %
      of infants, and this failure rate goes up to 30 % in infants born to highly
      viremic mothers. Mothers with HBV DNA levels above 200,000 IU/mL should be
      managed aggressively with antiviral therapy because viral load is the strongest
      independent risk factor for immunoprophylaxis failure. Emerging data suggest that
      initiation of antiviral therapy in late pregnancy in highly viremic mothers can
      prevent immunoprophylaxis failure in their infants. Reducing viral load to target
      levels below 200,000 IU/mL at delivery is a practical approach to control MTCT.
      This review focuses on viral factors in mothers associated with MTCT.

PMID- 29027109
TI  - Scenarios to manage the hepatitis C disease burden and associated economic impact
      of treatment in Turkey.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is a significant health problem.
      The aim of this study is to evaluate the cost-effectiveness of HCV treatment and
      estimate its economic burden in Turkey. METHODS: An Excel-based disease
      progression model was used to estimate the HCV-infected population for 2015-2030.
      Direct costs in US dollars (USD) including diagnostic, laboratory, and healthcare
      costs were provided by experts in the country. Indirect costs were estimated as
      lost productivity using the World Health Organization (WHO) disability-adjusted
      life years (DALYs) metric from the Global Burden of Disease study. Three
      scenarios were developed to estimate the cost-effectiveness of HCV treatment
      through 2030: Base 2016, Increase Treatment and SVR (where SVR is sustained
      virological response), and WHO Targets. Additionally, the WHO Targets scenario
      was assessed at three different treatment price points: 10,900 USD, 16,730 USD
      (base cost), and 27,285 USD. RESULTS: Cumulative total direct and indirect costs
      (2015-2030) for the WHO Targets scenario were estimated to be 10.8 billion USD,
      or a 1.5 % increase compared with Base 2016. However, by the following decade,
      due to a marked decline in DALYs, cumulative direct and indirect costs were
      estimated to be 45 % less when compared with Base 2016. At a threshold of 9125
      USD, all scenarios were cost-effective. CONCLUSIONS: By implementing the WHO
      Targets scenario, Turkey would be able to lower HCV prevalence by 80 % and reduce
      the total number of liver-related deaths by >65 % by 2030. Treating HCV infection
      in the country is cost-effective if healthcare and indirect costs are taken into
      consideration.

PMID- 29027108
TI  - Prognostic value of genetic mutations in adolescent and young adults with acute
      myeloid leukemia.
AB  - Clinical outcomes and the genetic background of acute myeloid leukemia (AML) in
      adolescent and young adults (AYAs) are known to differ in younger children and
      older adults. To clarify the impact of genetic mutations on clinical outcomes of
      AYAs with AML, we analyzed data from the JPLSG AML-05 and JALSG AML201 studies.
      AYAs aged 15-39 years (n = 103) were included. FLT3-ITD, KIT, CEBPA, NRAS, KRAS,
      WT1, MLL-PTD, and NPM1 mutations were analyzed. Overall survival (OS) of the AYAs
      was 61% and event-free survival was 38% at 3 years. FLT3-ITD (HR 2.10; 95% CI
      1.07-4.12; p = 0.031) and NPM1 (HR 0.24; 95% CI 0.06-1.00; p = 0.050) mutations
      were associated with risk of overall mortality in multivariate analysis. OS was
      significantly different according to FLT3-ITD and NPM1 mutation status (p =
      0.03). Survival was 100% with NPM1 mutations in the absence of FLT3-ITD and 35%
      (95% CI 14-57%) with FLT3-ITD in the absence of NPM1 mutations. The OS of AYAs,
      children (n = 413) and older adults (n = 124) of the AML-05 and AML201
      participants were significantly different (p < 0.0001). This is the first report
      to combine clinical and genetic data of AYA AML from the major Japanese pediatric
      and adult study groups.

PMID- 29027110
TI  - Predicting the cancer burden in Catalonia between 2015 and 2025: the challenge of
      cancer management in the elderly.
AB  - BACKGROUND: Developing effective cancer control programmes requires information
      on the future cancer burden in an ageing population. In our study we predicted
      the burden of cancer in Catalonia from 2015 to 2025. METHODS: Bayesian age-period
      cohort models were used to predict the burden of cancer from 2015 to 2025 using
      incidence data from the Girona and Tarragona cancer registries and cancer
      mortality data from the Catalan mortality registry. Using the Bashir-Esteve
      method, we divided the net change in the number of cases between 2015 and 2025
      into changes due to population size (S), cancer risk (R) and age (A)
      distribution. RESULTS: By 2025, there will be 21,743 new cancer cases in men (40%
      aged > 74 years) and 17,268 in women (37% aged > 74 years). More than 40% of the
      new cases will be diagnosed among population aged 74 and older in prostate,
      colorectal, lung, bladder, pancreatic and stomach cancers in men, and in
      colorectal, pancreatic and bladder cancers and leukaemia in women. During 2015
      2025, the number of new diagnoses will increase by 5.5% in men (A + R + S = 18.1%
      - 13.3% + 0.7% = 5.5%) and 11.9% in women (A + R + S = 12.4% - 1.1% + 0.6% =
      11.9%). Overall cancer mortality rates will continue to decrease during 2015
      2025. Lung cancer will be the most lethal cancer among men (N = 2705) and women
      (N = 1174). CONCLUSIONS: The increase in the number of cancer cases in Catalonia
      from 2015 to 2025 will mostly affect the elderly, prompting the need for
      increased collaboration between geriatricians and oncologists.

PMID- 29027111
TI  - Excessive D1 Dopamine Receptor Activation in the Dorsal Striatum Promotes
      Autistic-Like Behaviors.
AB  - The dopamine system has been characterized in motor function, goal-directed
      behaviors, and rewards. Recent studies recognize various dopamine system genes as
      being associated with autism spectrum disorder (ASD). However, how dopamine
      system dysfunction induces ASD pathophysiology remains unknown. In the present
      study, we demonstrated that mice with increased dopamine functions in the dorsal
      striatum via the suppression of dopamine transporter expression in substantia
      nigra neurons or the optogenetic stimulation of the nigro-striatal circuitry
      exhibited sociability deficits and repetitive behaviors relevant to ASD pathology
      in animal models, while these behavioral changes were blocked by a D1 receptor
      antagonist. Pharmacological activation of D1 dopamine receptors in normal mice or
      the genetic knockout (KO) of D2 dopamine receptors also produced typical autistic
      like behaviors. Moreover, the siRNA-mediated inhibition of D2 dopamine receptors
      in the dorsal striatum was sufficient to replicate autistic-like phenotypes in D2
      KO mice. Intervention of D1 dopamine receptor functions or the signaling pathways
      related D1 receptors in D2 KO mice produced anti-autistic effects. Together, our
      results indicate that increased dopamine function in the dorsal striatum promotes
      autistic-like behaviors and that the dorsal striatum is the neural correlate of
      ASD core symptoms.

PMID- 29027113
TI  - Anemia and hypogammaglobulinemia caused by Menetrier's disease.

PMID- 29027114
TI  - Trends in the clinical stage distribution of breast cancer in Osaka, Japan.
AB  - We examined the proportion of screen-detected breast cancer cases and clinical
      stage distribution by age group among female breast cancer cases in Osaka, Japan
      using population-based cancer registry from the period 1980 to 2012. The
      proportion of local cases increased and that of regional cases decreased
      gradually during the study period. The proportion of distant cases leveled off.
      The proportion of in situ cases increased rapidly after 2003. This increase was
      noticeable for women aged 30-39, 40-49, 50-59, and 60-69 years. The proportion of
      in situ cases for women aged 40-49, 50-59, and 60-69 years reached 15.4, 11.3,
      and 9.9% in 2010-2012, respectively. Regarding screening status, the proportion
      of screen-detected cases before 1988 was under 3%. Between 1989 and 2003, it
      leveled off at around 5%. After 2003, the proportion increased noticeably, and
      reached 25.4%:34.0% in aged 40-49 years, 32.8% in aged 50-59 years, and 26.7% in
      aged 60-69 years. The increase in local cases and decrease in regional cases
      would be due to awareness of breast cancer, probably a result of developments in
      medical diagnostic technology. On the other hand, the steep increase of in situ
      cases might be due to screening. We need careful monitoring of the trends in
      breast cancer incidence by clinical stage.

PMID- 29027112
TI  - Field Synopsis and Re-analysis of Systematic Meta-analyses of Genetic Association
      Studies in Multiple Sclerosis: a Bayesian Approach.
AB  - To provide an up-to-date summary of multiple sclerosis-susceptible gene variants
      and assess the noteworthiness in hopes of finding true associations, we
      investigated the results of 44 meta-analyses on gene variants and multiple
      sclerosis published through December 2016. Out of 70 statistically significant
      genotype associations, roughly a fifth (21%) of the comparisons showed noteworthy
      false-positive rate probability (FPRP) at a statistical power to detect an OR of
      1.5 and at a prior probability of 10-6 assumed for a random single nucleotide
      polymorphism. These associations (IRF8/rs17445836, STAT3/rs744166, HLA/rs4959093,
      HLA/rs2647046, HLA/rs7382297, HLA/rs17421624, HLA/rs2517646, HLA/rs9261491,
      HLA/rs2857439, HLA/rs16896944, HLA/rs3132671, HLA/rs2857435, HLA/rs9261471,
      HLA/rs2523393, HLA-DRB1/rs3135388, RGS1/rs2760524, PTGER4/rs9292777) also showed
      a noteworthy Bayesian false discovery probability (BFDP) and one additional
      association (CD24 rs8734/rs52812045) was also noteworthy via BFDP computation.
      Herein, we have identified several noteworthy biomarkers of multiple sclerosis
      susceptibility. We hope these data are used to study multiple sclerosis genetics
      and inform future screening programs.

PMID- 29027115
TI  - Correlation between MRI and hip arthroscopy in children with Legg-Calve-Perthes
      disease.
AB  - BACKGROUND: Most of the information available about Legg-Calve-Perthes disease
      (LCPD) at present is gained through imaging modalities including plain
      radiographs and magnetic resonance imaging (MRI). But the accuracy of MRI in this
      disease and its predictive value to reveal various intra-articular pathologies is
      not known. We correlated the findings of MRI with those seen on hip arthroscopy
      in children with active stage of LCPD. METHODS: We conducted a prospective
      observational study in which MRI findings were correlated with corresponding
      findings on hip arthroscopy in a cohort of 25 patients of active LCPD below 12
      years of age. The parameters noted on MRI included status of ligamentum teres,
      status of the labrum, synovial effusion if any, condition of the femoral and
      acetabular articular cartilage including chondral flaps, chondral indentation and
      intra-articular loose bodies. The indication of performing hip arthroscopy was
      persistent severe hip pain (Wong-Baker FACES pain scale >= 3) after 6 months of
      conservative management. Sensitivity, specificity, positive predictive value
      (PPV) and negative predictive value (NPV) were calculated for MRI considering
      arthroscopy as a gold standard. RESULTS: Synovial effusion was seen in a large
      number of patients on both MRI (17) and hip arthroscopy (24). The sensitivity
      (95% confidence interval) of MRI was found to be low, especially with respect to
      labral tears [25% (0.63-80.6)] and intra-articular loose bodies [20% (0.51
      71.6)]. NPV for synovial effusion was also found to be low [12.5% (0.32-52.7)],
      although specificity and PPV of MRI were found to be good for all the parameters.
      CONCLUSIONS: MRI cannot be completely relied upon for identifying all the intra
      articular pathologies in children with LCPD, although it has a good complimentary
      role. In patients with severe persistent pain with suspicion for joint changes,
      hip arthroscopy can provide a safe and efficient procedure (better than MRI) for
      eliciting the associated joint pathology.

PMID- 29027118
TI  - Genetic Variation of pln Loci Among Probiotic Lactobacillus plantarum Group
      Strains with Antioxidant and Cholesterol-Lowering Ability.
AB  - In the present study, 14 different plantaricin-encoding genes of pln loci were
      studied and compared to available sequences from public domain database of
      probiotic Lactobacillus plantarum strains. Based upon the presence and absence of
      selected genes, pln locus was grouped into eight clusters. Further, quantitative
      real-time PCR (qRT-PCR) analysis for seven genes has discriminated the complex
      pln locus into five types which includes WCFS1 (in Lactobacillus plantarum subsp.
      plantarum MCC 2976 and MCC 2974 and Lactobacillus paraplantarum MCC 2978),
      closely related to J51 (in Lb. paraplantarum MCC 2973 and MCC 2977), J23 (in Lb.
      plantarum MTCC 5422), NC8 (in Lb. paraplantarum MTCC 9483), and a new E1 type (in
      Lb. plantarum subsp. plantarum E1). It was observed that the plnA, EF,
      NC8betaalpha, NC81F, NC8HK, and G were expressed in E1 strain. Further, southern
      hybridization confirmed the chromosome-encoded plantaricin in Lb. plantarum group
      (LPG) strains. Several PCR assays and DNA sequence analysis of the regions
      amplified in pln loci of E1 isolate suggested a hybrid variant of NC8 and J51
      plantaritypes. This indicates the wide distribution of plantaricin with
      remarkable variation, diversity, and plasticity among the LPG strains of
      vegetable origin. Further, the selected strains were able to reduce the growth of
      Kocuria rhizophila ATCC 9341 by 40-54% within 6 h of co-incubation under in vitro
      pathogen exclusion assay. These isolates also possessed cholesterol-lowering and
      antioxidant activity suggesting their application in the development of
      functional foods.

PMID- 29027117
TI  - Immature platelet fraction (IPF) as a predictive value for thrombopoietic
      recovery after allogeneic stem cell transplantation.
AB  - We consecutively examined the utility of measurements of percentage of immature
      platelet fraction (IPF%) and absolute IPF number (A-IPF) in predicting
      thrombopoietic recovery in 15 adult patients who underwent allogeneic
      hematopoietic stem cell transplantation (allo-SCT). Four patients were excluded
      from the evaluation due to insufficient data. Platelet count and IPF were
      measured by Sysmex XN-1000 (XN), a newer generation analyzer. First, we confirmed
      that platelet count measured by XN was more accurate than by XE-2100 (XE). IPF
      measurement was effective to predict the recovery in 7 of the 11 patients
      examined. Moreover, IPF measurement, especially IPF% measurement, suggested
      accelerated platelet turnover in two patients who failed to achieve platelet
      recovery by day 60. In addition to IPF%, A-IPF showed a complementary role on the
      prediction of thrombopoietic recovery. The increase in IPF% was only transient,
      while A-IPF values showed lasting increase during platelet recovery. In two
      patients (cases 6 and 7) an increase in A-IPF, but not in IPF%, was observed
      during platelet recovery. Our data suggest that IPF% and A-IPF measured by XN are
      useful for the prediction of thrombopoietic recovery and the assessment of
      pathogenesis of thrombocytopenia in patients after allo-SCT.

PMID- 29027116
TI  - Effect of Intracoronary and Intravenous Melatonin on Myocardial Salvage Index in
      Patients with ST-Elevation Myocardial Infarction: a Randomized Placebo Controlled
      Trial.
AB  - Melatonin has attenuated myocardial ischemia reperfusion injury in experimental
      studies. We hypothesized that the administration of melatonin during acute
      myocardial reperfusion improves myocardial salvage index in patients with ST
      elevation myocardial infarction. Patients (n = 48) were randomized in a 1:1 ratio
      to intracoronary and intravenous melatonin (total 50 mg) or placebo. The
      myocardial salvage index assessed by cardiac magnetic resonance imaging at day 4
      (+/- 1 day) after primary percutaneous coronary intervention was similar in the
      melatonin group (n = 22) at 55.3% (95% CI 47.0-63.6) and the placebo group (n =
      19) at 61.5% (95% CI 57.5-65.5), p = 0.21. The levels of high-sensitive troponin
      T, creatinine kinase myocardial band, and oxidative biomarkers (advanced
      oxidation protein products, malondialdehyde, myeloperoxidase) were similar in the
      groups. The frequency of clinical events at 90 days did not differ between the
      groups. In conclusion, melatonin did not improve the myocardial salvage index
      after primary percutaneous coronary intervention in patients with ST elevation
      myocardial infarction compared with placebo.

PMID- 29027119
TI  - Mollugin enhances the osteogenic action of BMP-2 via the p38-Smad signaling
      pathway.
AB  - Bone morphogenetic protein 2 (BMP-2) has been used clinically to encourage bone
      regeneration; although, there can be major side effects with larger doses.
      Therefore, there is a need to identify new small molecules to potentiate the
      osteogenic action of BMP-2. In this study, we investigated the effect of mollugin
      on bone formation in murine bi-potential mesenchymal progenitor C2C12 cells by
      combination with BMP-2. We found mollugin could enhance the BMP-2-mediated
      osteoblast differentiation of C2C12 cells. This was accompanied by the induction
      of other osteogenic BMPs. We also found the enhancing potential of mollugin may
      involve activation of the p38-Smad1/5/8 signaling axis. Furthermore, mollugin
      promoted skeletal development in zebrafish. The combination of BMP-2 with small
      molecules, including mollugin, could minimize its clinical limitations, and these
      molecules might lead to the development of effective stem cell stimulants for
      bone regeneration and fracture healing.

PMID- 29027121
TI  - Harnessing the Effect of pH on Lipid Production in Batch Cultures of Yarrowia
      lipolytica SKY7.
AB  - The objective of this research was to investigate the kinetics of lipid
      production by Yarrowia lipolytica SKY7 in the crude glycerol-supplemented media
      with and without the control of pH. Lipid and citric acid production were
      improved with the pH control condition. There was no significant difference
      observed in the biomass concentration with or without the pH control. In the pH
      controlled experiments, the biomass and lipid concentration reached 18 and 7.78
      g/L, (45.5% w/w), respectively, with lipid yield (Yp/s) of 0.179 g/g at 60 h of
      fermentation. The lipid production was directly correlated with growth and the
      process was defined as growth associated. After 60 h of fermentation, the lipid
      degradation was noticed in the pH-controlled reactor whereas it occurred after 84
      h in the pH-uncontrolled reactor. Apart from lipid, citric acid was produced as
      the major extracellular product in both fermentations but the much lower
      concentration in uncontrolled pH. Based on the experimental results, it is
      evident that controlling the pH will enhance the lipid production by 15% compared
      to pH-uncontrolled fermentation.

PMID- 29027122
TI  - Hi1a as a Novel Neuroprotective Agent for Ischemic Stroke by Inhibition of Acid
      Sensing Ion Channel 1a.
AB  - Strokes are the second-leading cause of death worldwide, and the cellular and
      molecular mechanisms underlying stroke-induced brain damage are still uncertain.
      The present therapy for acute ischemic stroke is limited to thrombolysis with the
      recombinant tissue plasminogen activator (rtPA). However, rtPA has a narrow
      therapeutic timeframe of 3-4.5 h, and only approximately 5% of stroke patients
      can benefit from rtPA treatment. Neuroprotective agents, such as N-methyl-D
      aspartate receptor antagonists, have shown great promise in preclinical studies.
      However, due to a limited therapeutic time window and/or intolerable side
      effects, they have failed in clinical trials. Extending the time window and
      reducing side effects for neuroprotective drugs against strokes are critical for
      effective therapy for stroke patients. A recent study published in Proceedings of
      the National Academy of Sciences by Irene R. Chassagnon et al. (2017) indicates
      that Hi1a, a disulfide-rich spider venom peptide, is a highly neuroprotective
      agent in both in vitro and in vivo studies against experimental stroke. Hi1a
      reveals neuroprotection through inhibition of acid-sensing ion channel 1a. Thus,
      Hi1a might be a promising neuroprotective agent to protect the brain from
      ischemic injury in humans.

PMID- 29027120
TI  - Elucidating the Preadipocyte and Its Role in Adipocyte Formation: a Comprehensive
      Review.
AB  - Adipogenesis is a complex process whereby the multipotent adipose-derived stem
      cell is converted to a preadipocyte before terminal differentiation into the
      mature adipocyte. Preadipocytes are present throughout adult life, exhibit
      adipose fat depot specificity, and differentiate and proliferate from distinct
      progenitor cells. The mechanisms that promote preadipocyte commitment and
      maturation involve numerous protein factor regulators, epigenetic factors, and
      miRNAs. Detailed characterization of this process is currently an area of intense
      research and understanding the roles of preadipocytes in tissue plasticity may
      provide insight into novel approaches for tissue engineering, regenerative
      medicine and treating a host of obesity-related conditions. In the current study,
      we analyzed the current literature and present a review of the characteristics of
      transitioning adipocytes and detail how local microenvironments influence their
      progression towards terminal differentiation and maturation. Specifically, we
      detail the characterization of preadipocyte via surface markers, examine the
      signaling cascades and regulation behind adipogenesis and cell maturation, and
      survey their role in tissue plasticity and health and disease.

PMID- 29027123
TI  - Pluripotent stem cells secrete Activin A to improve their epiblast competency
      after injection into recipient embryos.
AB  - It is not fully clear why there is a higher contribution of pluripotent stem
      cells (PSCs) to the chimera produced by injection of PSCs into 4-cell or 8-cell
      stage embryos compared with blastocyst injection. Here, we show that not only
      embryonic stem cells (ESCs) but also induced pluripotent stem cells (iPSCs) can
      generate F0 nearly 100% donor cell-derived mice by 4-cell stage embryo injection,
      and the approach has a "dose effect". Through an analysis of the PSC-secreted
      proteins, Activin A was found to impede epiblast (EPI) lineage development while
      promoting trophectoderm (TE) differentiation, resulting in replacement of the EPI
      lineage of host embryos with PSCs. Interestingly, the injection of ESCs into
      blastocysts cultured with Activin A (cultured from 4-cell stage to early
      blastocyst at E3.5) could increase the contribution of ESCs to the chimera. The
      results indicated that PSCs secrete protein Activin A to improve their EPI
      competency after injection into recipient embryos through influencing the
      development of mouse early embryos. This result is useful for optimizing the
      chimera production system and for a deep understanding of PSCs effects on early
      embryo development.

PMID- 29027125
TI  - A survey of modulated radiotherapy use in Australia & New Zealand in 2015.
AB  - A survey of radiation oncology medical physics departments across Australia and
      New Zealand was conducted to assess the usage, commissioning and quality
      assurance of modulated radiotherapy techniques such as IMRT and VMAT. Survey
      responses were collected in April-May 2015 to snapshot current practice and
      historical implementation. The survey asked 142 questions, and is the most
      detailed survey of its kind published to date. Analysis of results at overall
      department level, as well as sub-analysis for different equipment and techniques
      in use, was performed. Results show a high prevalence of IMRT and VMAT in use,
      and demonstrate the large heterogeneity in clinical practice and experience
      across the region.

PMID- 29027124
TI  - TAK1 inhibition ameliorates survival from graft-versus-host disease in an
      allogeneic murine marrow transplantation model.
AB  - Acute graft-versus-host disease (GVHD) is a major cause of morbidity and
      mortality in allogeneic hematopoietic cell transplantation (allo-HCT). Majority
      of the current immunosuppressive strategies targeting donor T cells to prevent or
      treat acute GVHD are only partially effective, and often require escalated
      immunosuppressive therapy. Recent studies have revealed that activation of
      antigen-presenting cells in the proinflammatory milieu is important for the
      priming and promotion of GVHD. This activation is mediated by innate immune
      signaling pathways, which therefore potentially represent new targets in
      addressing GVHD. Using gene expression analysis of peripheral monocytes from
      patients' post-allo-HCT, we detected an upregulation of TGF-beta-activated kinase
      1 (TAK1), a key regulator of the toll-like receptor signaling pathway. 5Z-7
      oxozeaenol, a selective inhibitor of TAK1, reduced proinflammatory cytokine
      production by activated monocytes under lipopolysaccharide stimulation and T cell
      proliferation in allogeneic-mixed leukocyte reactions with monocyte-derived
      dendritic cells. In an experimental mouse model of GVHD, 5Z-7-oxozeaenol
      administration after allo-HCT ameliorated GVHD severity and mortality, with
      significant reduction in serum TNFalpha, IL-1beta, and IL-12 levels. Our findings
      suggest that altering the activation status of innate immune cells by TAK1
      inhibition may be a novel therapeutic approach for acute GVHD.

PMID- 29027126
TI  - Etiology and Risk Factors Determining Poor Outcome of Severe Pneumonia in Under
      Five Children.
AB  - OBJECTIVES: To determine the etiology of severe pneumonia (pneumonia with chest
      indrawing) in under-five children, and to study the risk factors for poor
      outcomes viz., 'treatment failure', 'need for change in antibiotics', 'prolonged
      hospital stay', 'need for mechanical ventilation' and 'mortality.' METHODS:
      Children (age 2 mo to 5 y) with pneumonia and chest drawing were enrolled
      prospectively from October 2012 through September 2013. Clinical history was
      recorded, and examination, anthropometry and investigations (including chest X
      ray, blood culture and nasopharyngeal swab culture) were performed. Children were
      managed as per standard guidelines, and recovery outcomes were recorded in form
      of 'treatment failure' (defined as persistence of features of severe pneumonia
      after 72 h or worsening of clinical condition before 72 h), need for change of
      antibiotics and prolonged (>5 d) hospital stay. The associations between the
      clinical, anthropometric and diagnostic risk factors and the recovery outcomes
      were evaluated by univariate and multivariate logistic regression analysis.
      RESULTS: Out of 120 children enrolled in the study, 36 (42%) were culture
      positive (nasopharyngeal/blood); most common bacteria isolated were Streptococcal
      pneumoniae and Staphylococcal aureus, respectively. Treatment failure was seen in
      15 (12.5%), 34 (28.3%) needed change of antibiotics, and 50 (41.6%) children
      required prolonged hospitalization. Low birth weight, overcrowding, general
      danger signs (lethargy/unable to drink), clinical rickets, crepitation,
      leukocytosis and positive blood culture were significant risk factors for
      treatment failure, prolonged hospital stay and antibiotics change. On
      multivariate logistic regression analysis, respiratory rate of >70/min (OR 19.94,
      95%CI 1.42-280.29), lethargy/unconsciousness (OR 114.2, 95%CI 3.14-4147.92), and
      positive blood culture (OR 15.24, 95%CI 2.53-91.67) had more chances of treatment
      failure. Duration of hospital stay was prolonged in those who had inability to
      drink (OR 3.89, CI 1.37-10.99) or abnormal chest X-ray (OR 8.45, CI 3.56-20.04).
      Children with rickets (OR 3.69, CI 1.14-11.96), and those with abnormal chest X
      ray (OR 9.66, CI 2.62-35.53) had a higher odds of change in antibiotics. Presence
      of wheeze was a protective factor for treatment failure (OR 0.03, CI 0.00-0.37)
      and change of antibiotics (OR 0.24, CI 0.07-0.74). CONCLUSIONS: Staphylococcus
      aureus and Streptococcus pneumoniae are the predominant organisms causing severe
      pneumonia in our setting. Children with risk factors such as respiratory rate
      >70/min, rickets, lethargy/unconsciousness, not able to drink, abnormal chest X
      ray or positive blood culture are likely to have a delayed recovery or need of
      change of antibiotics, whereas those with wheeze are likely to recover faster
      with less chances of treatment failure.

PMID- 29027127
TI  - Use of Supplementary Patient Education Material Increases Treatment Adherence and
      Satisfaction Among Acne Patients Receiving Adapalene 0.1%/Benzoyl Peroxide 2.5%
      Gel in Primary Care Clinics: A Multicenter, Randomized, Controlled Clinical
      Study.
AB  - INTRODUCTION: Poor adherence to acne treatment may lead to unnecessary
      treatments, increased healthcare costs, and reduced quality of life (QoL). This
      multicenter study evaluated the effect of supplementary patient education
      material (SEM) (a short video, information card, and additional information
      available online) on treatment adherence and satisfaction among acne patients
      treated with the fixed-dose combination adapalene 0.1%/benzoyl peroxide 2.5% gel
      (A/BPO) in primary care clinics versus (1) standard-of-care patient education
      (SOCPE) (package insert and oral instruction) and (2) SOCPE plus more frequent
      clinic visits. METHODS: Subjects with acne were randomized to receive once-daily
      A/BPO for 12 weeks plus (1) SEM in addition to SOCPE; (2) SOCPE only with two
      additional visits; or (3) SOCPE only. Other assessments included a subject
      appreciation questionnaire, a physician questionnaire, and safety. RESULTS:
      Ninety-seven subjects were enrolled. At baseline, most (87.6%) had mild to
      moderate acne. Better adherence was observed in the A/BPO + SEM group compared
      with A/BPO + more visits or A/BPO alone [mean 63.1%, 48.2% (p = 0.0206), and
      56.5%, respectively]. The A/BPO + SEM group had more subjects with greater than
      75% adherence (45%, 30.4%, and 25%, respectively). According to the subject
      appreciation questionnaire, the SEM was more helpful to adhere to treatment
      (56.7%) versus more visits (32.3%) and A/BPO alone (15.2%), better use the
      product (70%, 61.3%, and 54.5%, respectively), and better manage skin irritation
      (53.3%, 48.4%, and 36.4%, respectively). All physicians were satisfied with the
      SEM and 90% would consider using it in their practice. Safety assessment showed
      fewer treatment-related adverse events in the A/BPO + SEM group. CONCLUSION: Use
      of the SEM may increase adherence of acne patients treated with once-daily A/BPO
      gel in primary care, consequently improving treatment and QoL in the long term.
      FUNDING: Nestle Skin Health-Galderma R&D. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT02307266.

PMID- 29027128
TI  - Continuous Infusion Versus Intermittent Bolus of Beta-Lactams in Critically Ill
      Patients with Respiratory Infections: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Critically ill patients display altered pharmacokinetics and
      pharmacodynamics and are more likely to be infected with more resistant
      pathogens. Beta-lactam antibiotics exhibit time-dependent pharmacodynamics;
      therefore, it is postulated that continuous infusion (CI) may optimize these
      parameters. OBJECTIVE: To perform a systematic review and meta-analysis of the
      available literature comparing CI versus intermittent bolus (IB) of beta-lactam
      antibiotics in critically ill adult patients with respiratory infections to
      determine if clinical benefits exist. METHODS: PubMed, EMBASE, and Web of Science
      were searched. Thirteen randomized controlled trials were included in the meta
      analyses of clinical cure and/or mortality. Four retrospective studies reporting
      clinical cure and/or mortality, and 11 studies that reported
      pharmacokinetic/pharmacodynamic parameters were included in the systematic
      review. RESULTS: The majority of patients in both groups maintained the
      percentage of time the free drug concentration exceeded the minimum inhibitory
      concentration (%fT > MIC) targets throughout the treatment, with differences
      favoring CI being more prevalent when the MIC of the offending pathogen
      increased. CI of beta-lactam antibiotics in critically ill adult patients with
      respiratory infections significantly improved clinical cure rates when compared
      to IB (risk ratio [RR] 1.177; 95% CI 1.065-1.300). No significant differences in
      mortality rates were seen when patients were treated with either dosing modality
      (RR 0.845; 95% CI 0.644-1.108). CONCLUSIONS: CI of beta-lactam antibiotics is
      associated with better cure rates and higher %fT > MIC when administered to
      critically ill patients with respiratory infections, but may be most beneficial
      in severely ill patients with more resistant Gram-negative bacterial infections.

PMID- 29027129
TI  - Protein-Glass Surface Interactions and Ion Desalting in Electrospray Ionization
      with Submicron Emitters.
AB  - Theta glass electrospray emitters can rapidly mix solutions to investigate fast
      reactions that occur as quickly as 1 MUs, but emitters with submicron tips have
      the unusual properties of desalting protein ions and affecting the observed
      abundances of some proteins as a result of protein-surface interactions. The role
      of protein physical properties on ion signal was investigated using 1.7 +/- 0.1
      MUm and 269 +/- 7 nm emitters and 100 mM aqueous ammonium acetate or ammonium
      bicarbonate solutions. Protein ion desalting occurs for both positive and
      negative ions. The signal of a mixture of proteins with the 269 nm tips is time
      dependent and the order in which ions of each protein is observed is related to
      the expected strengths of the protein-surface interactions. These results
      indicate that it is not just the high surface-to-volume ratio that plays a role
      in protein adsorption and reduction or absence of initial ion signal, but the
      small diffusion distance and extremely low flow rates of the smaller emitters can
      lead to complete adsorption of some proteins and loss of signal until the
      adsorption sites are filled and the zeta potential is significantly reduced.
      After about 30 min, signals for a protein mixture from the two different size
      capillaries are similar. These results show the advantages of submicron emitters
      but also indicate that surface effects must be taken into account in experiments
      using such small tips or that coating the emitter surface to prevent adsorption
      should be considered. Graphical Abstract.

PMID- 29027130
TI  - Quality Issues Identified During the Evaluation of Biosimilars by the European
      Medicines Agency's Committee for Medicinal Products for Human Use.
AB  - The aim of this study was to identify trends in deficiencies raised during the EU
      evaluation of the quality part of dossiers for marketing authorisation
      applications of biosimilar medicinal products. All adopted day 120 list of
      questions on the quality module of 22 marketing authorisation applications for
      biosimilars submitted to the European Medicines Agency and concluded by the end
      of October 2015 was analysed. Frequencies of common deficiencies identified were
      calculated and summarised descriptions included. Frequencies and trends on
      quality deficiencies were recorded and presented for 22 biosimilar applications.
      Thirty-two 'major objections' for 9 products were identified from 14 marketing
      authorisation applications with 15 raised for drug substance and 17 for drug
      product. In addition, 547 'other concerns' for drug substance and 495 for drug
      product were also adopted. The frequencies and trends of the identified
      deficiencies together with their impact were discussed from a regulatory
      perspective and how these impact key manufacturing processes and key materials
      used in the production of biosimilars. This study provides an insight to the
      regulatory challenges prospective companies need to consider when developing
      biosimilars; it also helps elucidate common pitfalls in the development and
      production of biosimilars and in the submission of dossiers for their marketing
      authorisations. The results are expected to be of interest to pharmaceutical
      companies but also to regulators to obtain consistent information on medicinal
      products based on transparent rules safeguarding the necessary pharmaceutical
      quality of medicinal products.

PMID- 29027131
TI  - Selective BET Protein Inhibition with Apabetalone and Cardiovascular Events: A
      Pooled Analysis of Trials in Patients with Coronary Artery Disease.
AB  - BACKGROUND: Inhibition of bromodomain and extra-terminal (BET) proteins can
      modulate lipoprotein and inflammatory factors that mediate atherosclerosis. The
      impact of the BET inhibitor, apabetalone, on cardiovascular events is unknown.
      OBJECTIVE: Our objective was to investigate the impact of apabetalone on
      cardiovascular event rates in a pooled analysis of clinical studies in patients
      with established coronary artery disease. METHODS: We conducted a pooled analysis
      of patients (n = 798) with coronary artery disease who participated in clinical
      trials (ASSERT, ASSURE, SUSTAIN) that evaluated the impact of 3-6 months of
      treatment with apabetalone on lipid parameters and coronary atherosclerosis. The
      incidence of major adverse cardiovascular events (death, myocardial infarction,
      coronary revascularization, hospitalization for cardiovascular causes) in the
      treatment groups was evaluated. RESULTS: At baseline, patients treated with
      apabetalone were more likely to be Caucasian, have a history of dyslipidemia, and
      be undertreated with beta-blocker and anti-platelet agents. Treatment with
      apabetalone produced the following dose-dependent changes compared with placebo:
      increases in apolipoprotein A-I (apoA-I) of up to 6.7% (P < 0.001), increases in
      high-density lipoprotein cholesterol (HDL-C) of up to 6.5% (P < 0.001), increases
      in large HDL particles of up to 23.3% (P < 0.001), and decreases in high
      sensitivity C-reactive protein (hsCRP) of - 21.1% (P = 0.04). Apabetalone
      treatment did not affect atherogenic lipoproteins compared with placebo. Patients
      treated with apabetalone experienced fewer major adverse cardiovascular events
      than those treated with placebo (5.9 vs. 10.4%; P = 0.02), a finding that was
      more prominent in patients with diabetes (5.4 vs. 12.7%; P = 0.02), with baseline
      HDL-C < 39 mg/dl (5.5 vs. 12.8%; P = 0.01), or with elevated hsCRP levels (5.4
      vs. 14.2%; P = 0.02). CONCLUSION: Pooled analysis of short-term studies
      demonstrated fewer cardiovascular events among patients treated with the BET
      protein inhibitor, apabetalone, than among those treated with placebo. BET
      protein inhibition warrants further investigation as a novel approach to
      cardiovascular risk reduction.

PMID- 29027133
TI  - Combination of a chemopreventive agent and paclitaxel in CD44-targeted hybrid
      nanoparticles for breast cancer treatment.
AB  - The CD44 receptor, which is upregulated in many cancer cells, provides a
      selective cellular surface for targeted drug delivery systems. We developed a
      hybrid nanocarrier for the CD44-targeted delivery of ibuprofen (IBU) and
      paclitaxel (PTX). The solid lipid nanoparticles (SLNs) were prepared by a hot
      melt oil/water emulsion technique and then coated with hyaluronic acid (HA) by
      electrostatic interactions. The final SLN were spherical with a hydrodynamic
      diameter (Z) of 72.16 +/- 2.9 nm, polydispersity index (PDI) of 0.276 +/- 0.009,
      and zeta potential (ZP) of 28.20 +/- 0.69 mV. Similarly, SLN coated with HA (SLN
      HA) exhibited acceptable physical properties (Z 169.3 +/- 0.55 nm, PDI 0.285 +/-
      0.004, and ZP - 10.5 +/- 0.15 mV). Cell viability assays showed that the
      combination of IBU, a chemopreventive agent, and PTX exerted a synergistic
      inhibitory effect on the proliferation of cancer cells (CI < 1.0). Additionally,
      our observations indicated that both SLN and SLN-HA enhanced apoptosis and
      cellular uptake compared to the cocktail of free drugs. HA indicated its affinity
      for cancer cells through the improvement of cellular uptake and induction of
      apoptosis. These results clearly indicated that these nanoparticle systems hold
      great promise for drug delivery in breast cancer treatment.

PMID- 29027132
TI  - Submicrometer Emitter ESI Tips for Native Mass Spectrometry of Membrane Proteins
      in Ionic and Nonionic Detergents.
AB  - Native mass spectrometry (native-MS) of membrane proteins typically requires a
      detergent screening protocol, protein solubilization in the preferred detergent,
      followed by protein liberation from the micelle by collisional activation. Here,
      submicrometer nano-ESI emitter tips are used for native-MS of membrane proteins
      solubilized in both nonionic and ionic detergent solutions. With the
      submicrometer nano-ESI emitter tips, resolved charge-state distributions of
      membrane protein ions are obtained from a 150 mM NaCl, 25 mM Tris-HCl with 1.1%
      octyl glucoside solution. The relative abundances of NaCl and detergent cluster
      ions at high m /z are significantly reduced with the submicrometer emitters
      compared with larger nano-ESI emitters that are commonly used. This technique is
      beneficial for significantly decreasing the abundances (by two to three orders of
      magnitude compared with the larger tip size: 1.6 MUm) of detergent cluster ions
      formed from aqueous ammonium acetate solutions containing detergents that can
      overlap with the membrane protein ion signal. Resolved charge-state distributions
      of membrane protein ions from aqueous ammonium acetate solutions containing ionic
      detergents were obtained with the submicrometer nano-ESI emitters; this is the
      first report of native-MS of membrane proteins solubilized by ionic detergents.
      Graphical Abstract.

PMID- 29027135
TI  - Does Coenzyme Q10 Supplementation Mitigate Statin-Associated Muscle Symptoms?
      Pharmacological and Methodological Considerations.
AB  - Statin drugs markedly reduce low-density lipoprotein cholesterol and consequently
      the incidence of cardiac events. In approximately 5-10% of adults, these drugs
      are associated with a range of muscle side effects such as muscle pain, cramping
      and weakness. Reduction in mitochondrial coenzyme Q10 (CoQ10), or ubiquinone, has
      been proposed as a mechanism for these statin-associated muscle symptoms (SAMS),
      and thus various formulations of CoQ10 are marketed and consumed for the
      prevention and treatment of SAMS. However, data supporting the efficacy of CoQ10
      are equivocal, with some studies showing that CoQ10 supplementation reduces the
      incidence and severity of SAMS and others finding no beneficial effects of
      supplementation. Methodological and pharmacological issues may confound
      interpretation of data on this topic. For example, many patients who report SAMS,
      such as those who have been enrolled in previous CoQ10 studies, may be
      experiencing non-specific (non-statin-associated) muscle pain. In addition, the
      effectiveness of oral CoQ10 supplementation to increase mitochondrial CoQ10 in
      human skeletal muscle is not well established. This manuscript will critically
      evaluate the published data on the efficacy of CoQ10 supplements in the
      prevention and treatment of SAMS.

PMID- 29027134
TI  - Topical thermal therapy with hot packs suppresses physical inactivity-induced
      mechanical hyperalgesia and up-regulation of NGF.
AB  - We focused on the analgesic effect of hot packs for mechanical hyperalgesia in
      physically inactive rats. Male Wistar rats were randomly divided into four
      groups: control, physical inactivity (PI), PI + sham treatment (PI + sham), and
      PI + hot pack treatment (PI + hot pack) groups. Physical inactivity rats wore
      casts on both hind limbs in full plantar flexed position for 4 weeks. Hot pack
      treatment was performed for 20 min a day, 5 days a week. Although mechanical
      hyperalgesia and the up-regulation of NGF in the plantar skin and gastrocnemius
      muscle were observed in the PI and the PI + sham groups, these changes were
      significantly suppressed in the PI + hot pack group. The present results clearly
      demonstrated that hot pack treatment was effective in reducing physical
      inactivity-induced mechanical hyperalgesia and up-regulation of NGF in plantar
      skin and gastrocnemius muscle.

PMID- 29027136
TI  - Oligonol promotes glucose uptake by modulating the insulin signaling pathway in
      insulin-resistant HepG2 cells via inhibiting protein tyrosine phosphatase 1B.
AB  - Insulin resistance and protein tyrosine phosphatase 1B (PTP1B) overexpression are
      strongly associated with type 2 diabetes mellitus (T2DM), which is characterized
      by defects in insulin signaling and glucose intolerance. In a previous study, we
      demonstrated oligonol inhibits PTP1B and alpha-glucosidase related to T2DM. In
      this study, we examined the molecular mechanisms underlying the anti-diabetic
      effects of oligonol in insulin-resistant HepG2 cells. Glucose uptake was assessed
      using a fluorescent glucose tracer, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4
      yl)amino]-2-deoxyglucose, and the signaling pathway was investigated by western
      blotting. Oligonol significantly increased insulin-provoked glucose uptake and
      decreased PTP1B expression, followed by modulation of ERK phosphorylation. In
      addition, oligonol activated insulin receptor substrate 1 by reducing
      phosphorylation at serine 307 and increasing that at tyrosine 895, and enhanced
      the phosphorylations of Akt and phosphatidylinositol 3-kinase. Interestingly, it
      also reduced the expression of two key enzymes of gluconeogenesis (glucose 6
      phosphatase and phosphoenolpyruvate carboxykinase), attenuated oxidative stress
      by scavenging/inhibiting peroxynitrite, and reactive oxygen species (ROS)
      generation, and augmented the expression of nuclear factor kappa B. These
      findings suggest oligonol improved the insulin sensitivity of insulin-resistant
      HepG2 cells by attenuating the insulin signaling blockade and modulating glucose
      uptake and production. Furthermore, oligonol attenuated ROS-related inflammation
      and prevented oxidative damage in our in vitro model of type 2 diabetes. These
      result indicate oligonol has promising potential as a treatment for T2DM.

PMID- 29027137
TI  - Cubic Liquid Crystalline Gels Based on Glycerol Monooleate for Intra-articular
      Injection.
AB  - In situ gels containing sinomenine hydrochloride (SMH) for intra-articular (IA)
      administration to treat rheumatoid arthritis (RA) were designed and investigated
      in this study. Glycerol monooleate (GMO) was used due to the potential to
      generate viscous crystalline phase structures upon water absorption. The gels
      were evaluated using different parameters: syringeability, gelation, viscosity,
      and drug release. And, polarized light microscopy (PLM), small-angle X-ray
      scattering investigation (SAXS), and rheological studies were used to analyze
      their internal structures. In vitro drug release studies were performed by the
      dialysis membrane diffusion method. The syringeability, viscosity, gelation time,
      and water for gelation of the obtained preparation met the requirements of IA
      injection. PLM, SAXS, and rheological analysis showed that all samples had
      transformed from flowable isotropic solution phases to the inverse cubic (V2)
      phases upon excess water. And, the gels were found to be able to maintain the
      drug release for more than 1 week. Results showed that in situ gels based on GMO
      liquid crystalline could provide a sustained system for SMH. Due to its sustained
      release, the in situ cubic gels were suitable for IA injection to treat RA.

PMID- 29027139
TI  - Correction to: Compositional Changes in Foliage Phenolics with Plant Age, a
      Natural Experiment in Boreal Forests.
AB  - The article Compositional Changes in Foliage Phenolics with Plant Age, a Natural
      Experiment in Boreal Forests, written by Hilde Karine Wam, Caroline Stolter and
      Line Nybakken, was originally published electronically on the publisher's
      internet portal (currently SpringerLink) on August 29, 2017 without open access.

PMID- 29027138
TI  - Recurrence of Optimally Treated Malignant Peritoneal Mesothelioma with
      Cytoreduction and Heated Intraperitoneal Chemotherapy.
AB  - BACKGROUND: The prognosis for patients with diffuse malignant peritoneal
      mesothelioma has dramatically improved with cytoreductive surgery and
      intraperitoneal chemotherapy. Little is known about disease recurrence after
      treatment. We analyzed the time to and predictors of recurrence in a large cohort
      of optimally treated patients. METHODS: We examined 113 patients completing a two
      stage cytoreduction and intraperitoneal chemotherapy protocol. All patients
      achieved optimal surgical resection with completeness of cytoreduction (CC) score
      <= 1 and were divided into two groups based on absence (Group A) or presence
      (Group B) of gross disease at the outset of the second operation. Predictors of
      disease recurrence and recurrence-free survival (RFS) were determined using Cox
      proportional hazard regression modeling, and estimates were obtained by using the
      Kaplan-Meier method. RESULTS: Forty-six percent of patients had no gross evidence
      of disease at the second operation; the remaining 54% were cytoreduced to CC <= 1
      (Group B). Forty-two percent of patients developed disease recurrence with a
      median recurrence-free survival of 38.5 months for the cohort; 79% of these
      received a form of iterative treatment. There was no statistically significant
      difference in recurrence-free survival between Group A (median RFS: 44.6 months)
      and B (median RFS: 35.5 months) (log-rank test, p = 0.06). Additionally, the only
      variable significantly associated with RFS was male gender (hazard ratio [HR]
      1.98, 95% confidence interval [CI] 1.16-3.38). CONCLUSIONS: Absence of gross
      disease at the second operation was not statistically protective against
      recurrence compared with presence of quantifiable residual disease (Group B) that
      was effectively cytoreduced. Long-term disease surveillance is recommended,
      because recurrence continues years after treatment. Where a question of
      recurrence arises on surveillance, males may benefit from a higher degree of
      suspicion.

PMID- 29027140
TI  - Biosafety and Antibacterial Ability of Graphene and Graphene Oxide In Vitro and
      In Vivo.
AB  - In recent years, graphene (G) and graphene oxide (GO) nanoparticles have begun to
      be applied in surgical implant surface modification. However, biosafety and
      antibacterial ability of G and GO are still unclear. In this study, the biosafety
      of G and GO in vitro was evaluated by co-culture with bone marrow mesenchymal
      stem cells (BMSCs) and biosafety in vivo was observed by implanting materials
      into mice muscle tissue. Biosafety results showed that 10 MUg/ml was the safety
      critical concentration for G and GO. When the concentration was more than 10
      MUg/ml, the cytotoxicity of G and GO showed a dose-dependent manner.Antibacterial
      results showed that G presented the antibacterial ability with the concentration
      equal to and more than 100 MUg/ml; GO presented the antibacterial ability with
      the concentration equal to and more than 50 MUg/ml. The antibacterial effect of G
      and GO were in a dose-dependent manner in vitro.The GO or G concentration between
      50 and 100 MUg/ml may be the better range to keep the balance of cytotoxicity and
      antibacterial ability. Our study reveals that G and GO have potential to be used
      in clinic with good biosafety and antibacterial properties in a certain
      concentration range.

PMID- 29027142
TI  - 55th Annual Symposium of the International Society for Clinical Electrophysiology
      of Vision (ISCEV 2017).

PMID- 29027144
TI  - Erratum to: Quantitative physiology and elemental composition of Kluyveromyces
      lactis CBS 2359 during growth on glucose at different specific growth rates.
AB  - In the original publication of the article, the below mentioned errors have
      appeared. The correct text is provided in this erratum, In the abstract section,
      the sentence "This dataset serve" should be replaced as "This dataset serves".
      Also, the reference "Basso TO, Gomes FS, Lopes ML, et al (2014) Homo- and
      heterofermentative lactobacilli differently affect sugarcane-based fuel ethanol
      fermentation. Antonie Van Leeuwenhoek 105:169-177. doi: 10.1007/s10482-013-0063-6
      " should be replaced as "Basso TO, Dario MG, Tonso A, Stambuk BU, Gombert AK
      (2010) Insufficient uracil supply in fully aerobic chemostat cultures of
      Saccharomyces cerevisiae leads to respiro-fermentative metabolism and double
      nutrient-limitation. Biotechnol Lett 32:973-977. doi: 10.1007/s10529-010-0248-2
      ". Finally, in the Table 2 footnote, "according to (Heijnen 1981)" should be
      replaced as "according to Heijnen (1981)".

PMID- 29027146
TI  - Correction to: JSH guideline for tumors of hematopoietic and lymphoid tissues
      lukemia: 4. Chronic myelogenous leukemia (CML)/myeloproliferative neoplasms
      (MPN).
AB  - In the original publication of this article, the "Acknowledgements" was not
      included and it is given below for your reading.

PMID- 29027145
TI  - Novel Biocompatible Au Nanostars@PEG Nanoparticles for In Vivo CT Imaging and
      Renal Clearance Properties.
AB  - Nanoprobes are rapidly becoming potentially transformative tools on disease
      diagnostics for a wide range of in vivo computed tomography (CT) imaging.
      Compared with conventional molecular-scale contrast agents, nanoparticles (NPs)
      promise improved abilities for in vivo detection. In this study, novel
      polyethylene glycol (PEG)-functionalized Au nanoparticles with star shape
      (AuNS@PEG) with strong X-ray mass absorption coefficient were synthesized as CT
      imaging contrast agents. Experimental results revealed that AuNS@PEG
      nanoparticles are well constructed with ultrasmall sizes, effective
      metabolisability, high computed tomography value, and outstanding
      biocompatibility. In vivo imaging also showed that the obtained AuNS@PEG
      nanoparticles can be efficiently used in CT-enhanced imaging. Therefore, the
      synthesized contrast agent AuNS@PEG nanoparticles as a great potential candidate
      can be widely used for CT imaging.

PMID- 29027147
TI  - Antonio J. Torres, MD, PhD.

PMID- 29027148
TI  - Safety of Russian-Backbone Trivalent, Live Attenuated Seasonal Influenza Vaccine
      in Healthy Subjects: Open-Label, Non-randomized Phase 4 Study.
AB  - INTRODUCTION AND AIM: A trivalent live attenuated influenza vaccine (Nasovac
      S(r)) was developed and licensed in India. A phase 4 study was conducted to
      assess safety. METHODOLOGY: This non-randomized, open-label, single-arm study
      among individuals >= 2 years of age involved administration of 0.5 mL of Nasovac
      S intranasally, with a 1-month follow-up after vaccination. Adverse events (AEs)
      were collected via structured diaries. RESULTS: Among 500 vaccinated subjects,
      160 were between 2 and 17 years of age, 240 were 18-49 years old and 100 were 50
      years and older. A total of 533 solicited reactions were reported. The majority
      of these reactions were mild, and almost all of them resolved without any
      sequelae. A total of 20% of subjects reported at least one local solicited
      reaction, and 23% reported at least one systemic solicited reaction. None of the
      45 unsolicited AEs reported by 37 subjects (7.4%) were causally related to the
      study vaccine. CONCLUSIONS: The data from the study adds to the existing safety
      database of Nasovac-S. REGISTRY: Clinical Trials Registry of India
      (CTRI/2015/08/006074).

PMID- 29027150
TI  - Obituary: Giovanni Davi (1948-2017).

PMID- 29027149
TI  - Sequencing Larger Intact Proteins (30-70 kDa) with Activated Ion Electron
      Transfer Dissociation.
AB  - The analysis of intact proteins via mass spectrometry can offer several benefits
      to proteome characterization, although the majority of top-down experiments focus
      on proteoforms in a relatively low mass range (<30 kDa). Recent studies have
      focused on improving the analysis of larger intact proteins (up to ~75 kDa), but
      they have also highlighted several challenges to be addressed. One major hurdle
      is the efficient dissociation of larger protein ions, which often to do not yield
      extensive fragmentation via conventional tandem MS methods. Here we describe the
      first application of activated ion electron transfer dissociation (AI-ETD) to
      proteins in the 30-70 kDa range. AI-ETD leverages infrared photo-activation
      concurrent to ETD reactions to improve sequence-informative product ion
      generation. This method generates more product ions and greater sequence coverage
      than conventional ETD, higher-energy collisional dissociation (HCD), and ETD
      combined with supplemental HCD activation (EThcD). Importantly, AI-ETD provides
      the most thorough protein characterization for every precursor ion charge state
      investigated in this study, making it suitable as a universal fragmentation
      method in top-down experiments. Additionally, we highlight several acquisition
      strategies that can benefit characterization of larger proteins with AI-ETD,
      including combination of spectra from multiple ETD reaction times for a given
      precursor ion, multiple spectral acquisitions of the same precursor ion, and
      combination of spectra from two different dissociation methods (e.g., AI-ETD and
      HCD). In all, AI-ETD shows great promise as a method for dissociating larger
      intact protein ions as top-down proteomics continues to advance into larger mass
      ranges. Graphical Abstract ?.

PMID- 29027151
TI  - Comparison of Different Ion Mobility Setups Using Poly (Ethylene Oxide) PEO
      Polymers: Drift Tube, TIMS, and T-Wave.
AB  - Over the years, polymer analyses using ion mobility-mass spectrometry (IM-MS)
      measurements have been performed on different ion mobility spectrometry (IMS)
      setups. In order to be able to compare literature data taken on different IM(-MS)
      instruments, ion heating and ion temperature evaluations have already been
      explored. Nevertheless, extrapolations to other analytes are difficult and thus
      straightforward same-sample instrument comparisons seem to be the only reliable
      way to make sure that the different IM(-MS) setups do not greatly change the gas
      phase behavior. We used a large range of degrees of polymerization (DP) of
      poly(ethylene oxide) PEO homopolymers to measure IMS drift times on three
      different IM-MS setups: a homemade drift tube (DT), a trapped (TIMS), and a
      traveling wave (T-Wave) IMS setup. The drift time evolutions were followed for
      increasing polymer DPs (masses) and charge states, and they are found to be
      comparable and reproducible on the three instruments. ?.

PMID- 29027152
TI  - Correction to: Reducing surgical site infections following total hip and knee
      arthroplasty: an Israeli experience.
AB  - In the original article, one of the co-author's family name has been published
      incorrectly.

PMID- 29027153
TI  - Conflicting Data on the Incidence of Leukopenia and Neutropenia After Heated
      Intraperitoneal Chemotherapy with Mitomycin C.
AB  - BACKGROUND: During heated intraperitoneal chemotherapy (HIPEC), neutropenia rates
      of 20 to 40% have been reported when mitomycin C (MMC) is dosed by weight or body
      surface area (BSA). This study investigated the authors' HIPEC experience using a
      fixed 40-mg dose of MMC, per consensus guidelines, and analyzed predictors for
      severe leukopenia and neutropenia. METHODS: Patients who underwent MMC-HIPEC from
      2007 to 2016 at a single tertiary care center were retrospectively reviewed.
      RESULTS: Among 314 MMC-HIPEC cases, 72 patients in the early era of the authors'
      program received routine prophylactic postoperative granulocyte-colony
      stimulating factor (GCSF). This early cohort had five severe leukopenic reactions
      and one neutropenic reaction. In the subsequent 242 cases without GCSF
      prophylaxis, severe leukopenia developed in 16 patients (7%), with neutropenia
      occurring in 11 (4.5%) of these cases. A history of prior systemic chemotherapy
      was noted in 9 (56%) of the 16 leukopenic patients compared with 112 (46%) of the
      patients who had no leukopenia (nonsignificant difference). The median nadir of
      leukopenia was 5 days (range 1-11 days). Of the 11 neutropenic patients, 6
      received therapeutic GCSF, and 5 recovered without intervention. The 30-day
      postoperative mortality of the patients with leukopenia was 0%. CONCLUSION: In
      this study, the incidence of neutropenia after HIPEC with 40 mg of MMC was
      markedly lower than reported in the literature for doses adjusted by BSA or
      weight. The authors report that GCSF is not necessary for routine prophylaxis of
      all MMC-HIPEC patients. The findings suggest that a fixed 40-mg dose of MMC
      allows HIPEC to be performed with less risk of immunosuppression.

PMID- 29027155
TI  - The role of T-cell immunoglobulin mucin-3 and its ligand galectin-9 in antitumor
      immunity and cancer immunotherapy.
AB  - Cancer treatment in the past few years has been transformed by a new kind of
      therapy that targets the immune system instead of the cancer itself to
      reinvigorate antitumor immunity with astonishing results. However, primary and
      acquired resistance to this type of treatment, namely immune checkpoint blockade
      (ICB), continue to counter treatment efficacy. In many cases, resistance has been
      attributed to defective or chronically enhanced interferon signaling and/or
      upregulation of alternative immune checkpoints, including T-cell immunoglobulin
      mucin-3 (Tim-3) and its ligand galactin-9 (Gal-9). In this article, we briefly
      describe the current knowledge of common checkpoint resistance mechanisms,
      focusing on the Tim-3/Gal-9 pathway as an alternative checkpoint that holds great
      promise as another target for ICB.

PMID- 29027156
TI  - Mapping bone marrow niches of disseminated tumor cells.
AB  - Breast cancer cells may disseminate early, before tumor diagnosis. Disseminated
      tumor cells, or DTCs, reside in the bone marrow, and may persist for years or
      even decades. Some of these cells may be re-activated to resume aggressive
      growth, and eventually become overt bone metastases. Recent studies have begun to
      shed light on this complicated process and revealed multiple steps and
      intermediate states of colonizing DTCs. However, how cancer-host interactions
      evolve during this process needs to be further understood. Most of our current
      knowledge of the bone microenvironment is obtained through studies looking for
      the hematopoietic stem cell (HSC) niche. Although this long-standing question has
      not yet been resolved, our search for the HSC niche has resulted in a detailed
      map of various cell types in the bone marrow. Furthermore, various techniques
      used to find the HSC niche may also be adapted for finding the cancer cell niche.
      In this article, we will review the recent progress in both the DTC and HSC areas
      with a focus on their potential microenvironment niches. We will also discuss how
      to apply what we have learned from HSC studies to map DTCs in the bone context.
      We hope to stimulate thoughts and ideas to further elucidate the bone
      colonization process, and develop potential therapeutic interventions.

PMID- 29027158
TI  - ISQ calculation evaluation of in vitro laser scanning vibrometry-captured
      resonance frequency.
AB  - BACKGROUND: Implant stability testing at various stages of implant therapy by
      means of resonance frequency analysis is extensively used. The overall
      measurement outcome is a function of the resulting stiffness of three entities:
      surrounding bone, bone-implant complex, and implant-Smartpeg complex. The
      influence of the latter on the overall measurement results is presently unknown.
      It can be investigated in vitro by use of imbedded implants with mounted
      Smartpegs. This enables to keep the influence of the two other entities constant
      and controlled. The purpose of this study is to verify if a laboratory laser
      Doppler vibrometry technology-based procedure results in comparable ISQ results
      after calculation of captured resonance frequency spectra by aid of the Osstell
      algorithm with direct Osstell IDX device measurements. METHODS: A laboratory
      procedure was engineered to record frequency spectra of resin-imbedded test
      implants with mounted Smartpegs, after electromagnetic excitation with the
      Osstell IDX device and laser Doppler vibrometry response detection. Fast Fourier
      transformation data processing of resonance frequency data resulted in
      determination of a maximum resonance frequency values allowing calculation of
      implant stability quotient (ISQ) values using the Osstell algorithm. RESULTS:
      Laboratory-based ISQ values were compared to Osstell IDx device-generated ISQ
      values for Straumann tissue level, Ankylos, and 3i Certain implant systems. For
      both systems, a correlation coefficient r = 0.99 was found. Furthermore, a
      clinically rejectable mean difference of 0.09 ISQ units was noted between both
      datasets. CONCLUSIONS: The proposed laboratory method with the application of the
      Osstell algorithm for ISQ calculation is appropriate for future studies to in
      vitro research aspects of resonance frequency analysis implant stability
      measurements.

PMID- 29027159
TI  - Correction to: Multifunctional decoration of alpha-tocopheryl succinate-based NP
      for cancer treatment: effect of TPP and LTVSPWY peptide.

PMID- 29027160
TI  - ChIP and ChIP-Related Techniques: Expanding the Fields of Application and
      Improving ChIP Performance.
AB  - Protein-DNA interactions in vivo can be detected and quantified by chromatin
      immunoprecipitation (ChIP). ChIP has been instrumental for the advancement of
      epigenetics and has set the groundwork for the development of a number of ChIP
      related techniques that have provided valuable information about the organization
      and function of genomes. Here, we provide an introduction to ChIP and discuss the
      applications of ChIP in different research areas. We also review some of the
      strategies that have been devised to improve ChIP performance.

PMID- 29027161
TI  - Considerations on Experimental Design and Data Analysis of Chromatin
      Immunoprecipitation Experiments.
AB  - Arguably one of the most valuable techniques to study chromatin organization,
      ChIP is the method of choice to map the contacts established between proteins and
      genomic DNA. Ever since its inception, more than 30 years ago, ChIP has been
      constantly evolving, improving, and expanding its capabilities and reach. Despite
      its widespread use by many laboratories across a wide variety of disciplines,
      ChIP assays can be sometimes challenging to design, and are often sensitive to
      variations in practical implementation.In this chapter, we provide a general
      overview of the ChIP method and its most common variations, with a special focus
      on ChIP-seq. We try to address some of the most important aspects that need to be
      taken into account in order to design and perform experiments that generate the
      most reproducible, high-quality data. Some of the main topics covered include the
      use of properly characterized antibodies, alternatives to chromatin preparation,
      the need for proper controls, and some recommendations about ChIP-seq data
      analysis.

PMID- 29027162
TI  - How to Combine ChIP with qPCR.
AB  - Chromatin immunoprecipitation (ChIP) coupled with quantitative PCR (qPCR) has in
      the last 15 years become a basic mainstream tool in genomic research. Numerous
      commercially available ChIP kits, qPCR kits, and real-time PCR systems allow for
      quick and easy analysis of virtually anything chromatin-related as long as there
      is an available antibody. However, the highly accurate quantitative dimension
      added by using qPCR to analyze ChIP samples significantly raises the bar in terms
      of experimental accuracy, appropriate controls, data analysis, and data
      presentation. This chapter will address these potential pitfalls by providing
      protocols and procedures that address the difficulties inherent in ChIP-qPCR
      assays.

PMID- 29027163
TI  - Analysis of Protein-DNA Interaction by Chromatin Immunoprecipitation and DNA
      Tiling Microarray (ChIP-on-chip).
AB  - Chromatin immunoprecipitation (ChIP) has become the most effective and widely
      used tool to study the interactions between specific proteins or modified forms
      of proteins and a genomic DNA region. Combined with genome-wide profiling
      technologies, such as microarray hybridization (ChIP-on-chip) or massively
      parallel sequencing (ChIP-seq), ChIP could provide a genome-wide mapping of in
      vivo protein-DNA interactions in various organisms. Here, we describe a protocol
      of ChIP-on-chip that uses tiling microarray to obtain a genome-wide profiling of
      ChIPed DNA.

PMID- 29027164
TI  - Chromatin Immunoprecipitation from Mouse Embryonic Tissue or Adherent Cells in
      Culture, Followed by Next-Generation Sequencing.
AB  - Chromatin immunoprecipitation (ChIP) is considered the method of choice for
      characterizing interactions between a protein of interest and specific genomic
      regions. It is of paramount importance in gene-regulation studies, as it can be
      used to map the target regions of sequence-specific transcription factors and
      cofactors, or histone marks that characterize distinct chromatin states. ChIP can
      be used directly to probe interactions with candidate regions (ChIP-PCR), or
      coupled to Next-Generation Sequencing (ChIP-seq) to generate genome-wide
      information. This chapter describes a protocol for performing ChIP and ChIP-seq
      of transcription factors, starting either from mouse embryonic tissue or adherent
      cells in culture.

PMID- 29027165
TI  - Chromatin RNA Immunoprecipitation (ChRIP).
AB  - Researchers have recently had a growing interest in understanding the functional
      role of long noncoding RNAs (lncRNAs) in chromatin organization. Accumulated
      evidence suggests lncRNAs could act as interphase molecules between chromatin and
      chromatin remodelers to define the epigenetic code. However, it is not clear how
      lncRNAs target chromatin remodelers to specific chromosomal regions in order to
      establish a functionally distinct epigenetic state of chromatin. We developed and
      optimized chromatin RNA immunoprecipitation (ChRIP) technology to characterize
      the lncRNAs associated with active and inactive chromatin compartments. Use of
      ChRIP to identify chromatin-bound lncRNA will further improve our knowledge
      regarding the functional role of lncRNAs in establishing epigenetic modifications
      of chromatin.

PMID- 29027166
TI  - DNA Accessibility by MNase Digestions.
AB  - Micrococcal nuclease (MNase) digestion of chromatin cuts linker DNA between
      neighboring nucleosomes and in this way generates mononucleosomes. The protected
      fragments can then be analyzed by genome-wide sequencing techniques or by
      quantitative PCR to obtain information about the positions of nucleosomes in the
      chromatin. Nucleosomes are differentially sensitive to MNase digestion, which
      means that titrations of MNase should be performed to obtain a comprehensive map
      of the nucleosome positions of a chromatin region or genome.

PMID- 29027167
TI  - Characterization of the Nucleosome Landscape by Micrococcal Nuclease-Sequencing
      (MNase-seq).
AB  - MNase-seq allows the genome-wide examination of the nucleosome landscape by
      determination of nucleosome positioning and occupancy. Typically, native or
      formaldehyde fixed chromatin is subjected to digestion by micrococcal nuclease
      (MNase), which degrades linker DNA and yields mainly mono-nucleosomes. The
      resulting material can be processed directly or can be subjected to an optional
      chromatin immunoprecipitation step (MNase-ChIP-seq). De-crosslinked and purified
      DNA is then subjected to next-generation sequencing. The protocol presented here
      has been tailored for the analysis of nucleosome landscape in the malaria
      parasite, Plasmodium falciparum, but most steps are directly applicable to other
      cell types. We also discuss general considerations for experimental design and
      computational analysis, which are crucial for accurate investigation of the
      nucleosome landscape.

PMID- 29027157
TI  - Animal models for bipolar disorder: from bedside to the cage.
AB  - Bipolar disorder is characterized by recurrent manic and depressive episodes.
      Patients suffering from this disorder experience dramatic mood swings with a wide
      variety of typical behavioral facets, affecting overall activity, energy, sexual
      behavior, sense of self, self-esteem, circadian rhythm, cognition, and increased
      risk for suicide. Effective treatment options are limited and diagnosis can be
      complicated. To overcome these obstacles, a better understanding of the
      neurobiology underlying bipolar disorder is needed. Animal models can be useful
      tools in understanding brain mechanisms associated with certain behavior. The
      following review discusses several pathological aspects of humans suffering from
      bipolar disorder and compares these findings with insights obtained from several
      animal models mimicking diverse facets of its symptomatology. Various sections of
      the review concentrate on specific topics that are relevant in human patients,
      namely circadian rhythms, neurotransmitters, focusing on the dopaminergic system,
      stressful environment, and the immune system. We then explain how these areas
      have been manipulated to create animal models for the disorder. Even though
      several approaches have been conducted, there is still a lack of adequate animal
      models for bipolar disorder. Specifically, most animal models mimic only mania or
      depression and only a few include the cyclical nature of the human condition.
      Future studies could therefore focus on modeling both episodes in the same animal
      model to also have the possibility to investigate the switch from mania-like
      behavior to depressive-like behavior and vice versa. The use of viral tools and a
      focus on circadian rhythms and the immune system might make the creation of such
      animal models possible.

PMID- 29027168
TI  - ChIP-re-ChIP: Co-occupancy Analysis by Sequential Chromatin Immunoprecipitation.
AB  - Chromatin immunoprecipitation (ChIP) exploits the specific interactions between
      DNA and DNA-associated proteins. It can be used to examine a wide range of
      experimental parameters. A number of proteins bound at the same genomic location
      can identify a multi-protein chromatin complex where several proteins work
      together to regulate gene transcription or chromatin configuration. In many
      instances, this can be achieved using sequential ChIP; or simply, ChIP-re-ChIP.
      Whether it is for the examination of specific transcriptional or epigenetic
      regulators, or for the identification of cistromes, the ability to perform a
      sequential ChIP adds a higher level of power and definition to these analyses. In
      this chapter, we describe a simple and reliable method for the sequential ChIP
      assay.

PMID- 29027169
TI  - Sm-ChIPi: Single-Molecule Chromatin Immunoprecipitation Imaging.
AB  - Epigenetic complexes regulate chromatin dynamics via binding to and assembling on
      chromatin. However, the mechanisms of chromatin binding and assembly of
      epigenetic complexes within cells remain incompletely understood, partly due to
      technical challenges. Here, we present a new approach termed single-molecule
      chromatin immunoprecipitation imaging (Sm-ChIPi) that enables to assess the
      cellular assembly stoichiometry of epigenetic complexes on chromatin. Sm-ChIPi
      was developed based on chromatin immunoprecipitation followed by single-molecule
      fluorescence microscopy imaging. In this method, an epigenetic complex subunit
      fused with a gene coding for a fluorescent protein is stably expressed in its
      corresponding knockout cells. Nucleosomes associated with epigenetic complexes
      are isolated from cells at native conditions and incubated with biotinylated
      antibodies. The resulting complexes are immobilized on a quartz slide that had
      been passivated and functionalized with NeutrAvidin. Image stacks are then
      acquired by using single-molecule TIRF microscopy. The individual spots imaged by
      TIRF microscopy represent single protein-nucleosome complexes. The number of
      copies of the protein complexes on a nucleosome is inferred from the fluorescence
      photobleaching measurements. Sm-ChIPi is a sensitive and direct method that can
      quantify the cellular assembly stoichiometry of epigenetic complexes on
      chromatin.

PMID- 29027170
TI  - Chromatin Immunoprecipitation of Skeletal Muscle Tissue.
AB  - Chromatin immunoprecipitation (ChIP) is an invaluable method for studying
      interactions between histone proteins and genomic DNA regions and transcriptional
      regulation using antibodies to enrich genomic regions associated with these
      epitopes. Either to monitor the presence of histones with post-translational
      modifications at specific genomic locations or to measure transcription factor
      interactions with a candidate target gene, protein-DNA complexes are most
      commonly crosslinked using formaldehyde, which stabilizes these transient
      interactions. Chromatin is then fragmented to allow separation of genomic
      fragments bound by the histone or transcription factor of interest away from
      those that are unbound. Following immunoprecipitation, formaldehyde crosslinks
      are reversed and enriched DNA fragments are purified. While some investigators
      have successfully performed ChIP experiments from crosslinked skeletal muscle in
      cell culture, the process is relatively inefficient compared to whole tissue.
      This chapter provides protocols specifically designed for the crosslinking and
      immunoprecipitation of human skeletal muscle biopsy samples in preparation for
      chromatin immunoprecipitation-sequencing (ChIP-seq).

PMID- 29027171
TI  - Chromatin Immunoprecipitation Assay in the Hyperthermoacidophilic Crenarchaeon,
      Sulfolobus acidocaldarius.
AB  - Chromatin immunoprecipitation (ChIP) is a powerful method used for identifying
      genome-wide DNA-protein interactions in vivo. A large number of essential
      intracellular processes such as DNA replication, transcription regulation,
      chromatin stability, and others are all dependent on protein interactions with
      DNA. The DNA fragments enriched from the ChIP assay are analyzed by downstream
      applications, for example, microarray hybridization (ChIP-chip), quantitative PCR
      (ChIP-qPCR), or deep sequencing (ChIP-seq). This chapter presents a stepwise
      protocol for ChIP performed in hyperthermophilic archaea that we have
      successfully used in the hyperthermoacidophilic crenarchaeon Sulfolobus
      acidocaldarius.

PMID- 29027173
TI  - Native Chromatin Immunoprecipitation-Sequencing (ChIP-Seq) from Low Cell Numbers.
AB  - ChIP-seq is the current method of choice for genome-wide protein location
      analysis. Here, we present a native (non-cross-linked) ChIP procedure suitable
      for histone proteins, coupled with an efficient library preparation technique for
      subsequent next-generation sequencing. The method enables ChIP-seq starting with
      50,000 or more cells.

PMID- 29027172
TI  - Using Intra-ChIP to Measure Protein-DNA Interactions in Intracellular Pathogens.
AB  - Chromatin immunoprecipitation is used to measure the binding of transcription
      factors to target DNA sequences in order to better understand transcriptional
      regulation. Here, we describe a process to analyze bacterial transcription factor
      binding in the context of an infected eukaryotic host cell. Using this approach,
      we measured the binding kinetics of three Chlamydia trachomatis transcription
      factors within infected cells, and demonstrated temporal changes in binding.

PMID- 29027174
TI  - MOBE-ChIP: Probing Cell Type-Specific Binding Through Large-Scale Chromatin
      Immunoprecipitation.
AB  - In multicellular organisms, the initiation and maintenance of specific cell types
      often require the activity of cell type-specific transcriptional regulators.
      Understanding their roles in gene regulation is crucial but probing their DNA
      targets in vivo, especially in a genome-wide manner, remains a technical
      challenge with their limited expression. To improve the sensitivity of chromatin
      immunoprecipitation (ChIP) for detecting the cell type-specific signals, we have
      developed the Maximized Objects for Better Enrichment (MOBE)-ChIP, where ChIP is
      performed at a substantially larger experimental scale and under low background
      conditions. Here, we describe the procedure in the study of transcription factors
      in the model plant Arabidopsis. However, with some modifications, the technique
      should also be implemented in other systems. Besides cell type-specific studies,
      MOBE-ChIP can also be used as a general strategy to improve ChIP signals.

PMID- 29027175
TI  - Multiplexed ChIP-Seq Using Direct Nucleosome Barcoding: A Tool for High
      Throughput Chromatin Analysis.
AB  - Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) or microarray
      hybridization (ChIP-on-chip) are standard methods for the study of transcription
      factor binding sites and histone chemical modifications. However, these
      approaches only allow profiling of a single factor or protein modification at a
      time.In this chapter, we present Bar-ChIP, a higher throughput version of ChIP
      Seq that relies on the direct ligation of molecular barcodes to chromatin
      fragments. Bar-ChIP enables the concurrent profiling of multiple DNA-protein
      interactions and is therefore amenable to experimental scale-up, without the need
      for any robotic instrumentation.

PMID- 29027176
TI  - Analysis of ChIP-seq Data in R/Bioconductor.
AB  - The development of novel high-throughput sequencing methods for ChIP (chromatin
      immunoprecipitation) has provided a very powerful tool to study gene regulation
      in multiple conditions at unprecedented resolution and scale. Proactive quality
      control and appropriate data analysis techniques are of critical importance to
      extract the most meaningful results from the data. Over the last years, an array
      of R/Bioconductor tools has been developed allowing researchers to process and
      analyze ChIP-seq data. This chapter provides an overview of the methods available
      to analyze ChIP-seq data based primarily on software packages from the open
      source Bioconductor project. Protocols described in this chapter cover basic
      steps including data alignment, peak calling, quality control and data
      visualization, as well as more complex methods such as the identification of
      differentially bound regions and functional analyses to annotate regulatory
      regions. The steps in the data analysis process were demonstrated on publicly
      available data sets and will serve as a demonstration of the computational
      procedures routinely used for the analysis of ChIP-seq data in R/Bioconductor,
      from which readers can construct their own analysis pipelines.

PMID- 29027177
TI  - Spike-In Normalization of ChIP Data Using DNA-DIG-Antibody Complex.
AB  - Chromatin immunoprecipitation (ChIP) is a widely used method to determine the
      occupancy of specific proteins within the genome, helping to unravel the function
      and activity of specific genomic regions. In ChIP experiments, normalization of
      the obtained data by a suitable internal reference is crucial. However,
      particularly when comparing differently treated samples, such a reference is
      difficult to identify. Here, a simple method to improve the accuracy and
      reliability of ChIP experiments by the help of an external reference is
      described. An artificial molecule, composed of a well-defined digoxigenin (DIG)
      labeled DNA fragment in complex with an anti-DIG antibody, is synthesized and
      added to each chromatin sample before immunoprecipitation. During the ChIP
      procedure, the DNA-DIG-antibody complex undergoes the same treatments as the
      chromatin and is therefore purified and quantified together with the chromatin of
      interest. This external reference compensates for variability during the ChIP
      routine and improves the similarity between replicates, thereby emphasizing the
      biological differences between samples.

PMID- 29027178
TI  - Mechanisms of regulation of normal and metaplastic intestinal differentiation.
AB  - The gastrointestinal tract is an organized structure originating from the three
      embryonic germ layers: endoderm, mesoderm and ectoderm. Morphological changes
      that accompany its formation are relatively well known, although the underlying
      molecular mechanisms are still poorly defined. Intestinal metaplasia, resulting
      from an epithelial transdifferentiation process, is considered a precursor lesion
      of gastric adenocarcinoma, a malignancy with serious consequences in terms of
      morbidity and mortality worldwide. Similarly to gastrointestinal embryonic
      development, molecular changes involved in the development of this lesion that
      recapitulate the intestinal development, out of time and space, are also widely
      unknown. In this review we present, briefly, the process of formation of the
      digestive tract, from its embryonic age to adulthood, with emphasis on anterior
      posterior patterning and on molecular mechanisms that may play an important role.
      In addition, we try to establish a parallel and understand what mechanisms can,
      through their deregulation, originate the metaplastic lesion. Cdx genes appear to
      be the main regulators of normal intestinal differentiation and also to be
      largely involved in the metaplastic epithelial transdifferentiation process.
      However, control of gene expression both during intestinal development and in
      intestinal metaplasia is complex and seems to depend on several transcription
      factors. More extensive studies about the mechanisms underlying intestinal
      metaplasia are needed if we aim to prevent neoplasia development and all its
      negative consequences in persons at risk.

PMID- 29027179
TI  - Association of DNMT3B -283T>C polymorphism with risk of lung and gastric cancer:
      a case-control study and a meta-analysis.
AB  - PURPOSE: To investigate the association of DNMT3B -283T>C polymorphism with the
      risk of lung or gastric cancer, which was followed by a meta-analysis. METHODS:
      The genotyping of -283T>C was performed by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) and was confirmed by sequencing. RESULTS:
      The results of this case-control study showed that -283T>C was not associated
      with the risk of lung or gastric cancer, and further stratified analysis
      according to age, gender, smoking status, and alcohol status confirmed the
      present finding. However, data from a meta-analysis in the Asian population
      revealed a significant association between -283T>C and lung cancer risk in the
      allelic model (C vs. T: odds ratio [OR] = 1.28, 95% confidence interval [CI],
      1.06-1.55, p = 0.01) and two genetic models (CC vs. TC: OR = 1.29, 95% CI, 1.04
      1.59, p = 0.02; CC vs. TC + TT: OR = 1.30, 95% CI, 1.06-1.60, p = 0.01).
      CONCLUSIONS: These results provided evidence that the DNMT3B -283T>C polymorphism
      might significantly contribute to the lung cancer risk in the Asian population,
      but not the gastric cancer risk in the Chinese population.

PMID- 29027180
TI  - Effect of ZrB2 addition on the oxidation behavior of Si-SiC-ZrB2 composites
      exposed at 1500 degrees C in air.
AB  - BACKGROUND: Silicon carbide ceramics obtained by reactive infiltration of silicon
      (SRI) have many industrial applications especially involving severe and high
      temperature conditions. In this study, the oxidation behavior in air of Si-SiC
      ZrB2 systems at a high temperature (1500 degrees C) for dwelling times of up to
      48 hours was examined. METHODS: The oxidation process was analyzed on the basis
      of elemental maps and X-ray diffraction patterns taken, respectively, on the core
      and on the surface of the specimens, together with weight gains and the average
      thicknesses of the resulting scale. Further, flexural strength at room
      temperature was examined as a function of different oxidation times. RESULTS: The
      main chemical reactions and phase transformations involved in the oxidation
      process are reported. Several oxides were detected on the surface: zirconia,
      silica, zircon and 3-zirconium monoxide. All of the samples showed a parabolic
      oxidation kinetics, suggesting that the controlling mechanism was the diffusion;
      however, even after 48 hours, the oxidation process was not finished - indeed,
      all of the samples continued to gain weight. CONCLUSIONS: The oxidation of Si-SiC
      ZrB2 material produced via SRI was slower compared with previously investigated
      ZrB2-SiC composites processed with a different techniques and tested in similar
      conditions. The oxidation mechanism was found to be consistent with the
      convection cells model.

PMID- 29027181
TI  - Excellent inter-observer agreement between radiologist and nurse: tracheal carina
      based identification of peripherally inserted central catheter tip position.
AB  - INTRODUCTION: Accurate identification of position of a central venous catheter
      tip is important to reduce catheter-related complications. Nevertheless, inter
      observer bias limits the accuracy of traditional method for determining tip
      position on chest x-ray (CXR) images. The aim of this study was to explore a
      simple and objective method for assessing position of peripherally inserted
      central catheter (PICC) tip on CXR image. METHODS: Tracheal carina was used as
      the landmark to identify positions of catheter tips. The central vein (CV) was
      located between 3 cm above and 4 cm below tracheal carina. The vertical distance
      from catheter tips to tracheal carina was measured independently by a nurse and
      re-assessed by a radiologist. Inter-observer agreement was expressed as
      percentage in agreement and kappa coefficient. RESULTS: Six hundred and twelve
      CXR images of catheters taken from 612 patients were included. The inter-observer
      agreement between nurse and radiologist was 97.88% (kappa = 0.934) for all
      catheter tips evaluated, and 98.40% (kappa = 0.923) for catheter tips with regard
      to CV, innominate vein, and right atrium. Most discrepancies (9/13) between
      observers occurred when catheter tips were positioned in a border region between
      different anatomical parts. CONCLUSIONS: Inter-observer agreement between nurse
      and radiologist is excellent. Our results demonstrate that the measurement of
      distance between catheter tip and tracheal carina performed by a nurse provide a
      convenient and reliable way to determine position of PICC tip. Our study also
      suggests that nurses can be trained to handle PICCs, especially when properly
      located catheters are applied in critically ill patients during emergency
      setting.

PMID- 29027182
TI  - Preoperative management of arteriovenous fistula (AVF) for hemodialysis.
AB  - Native arteriovenous fistula (AVF) is the favorite access for hemodialysis (HD).
      The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative
      (KDOQI) recommends its creation in most patients with renal failure.
      Unfortunately, intensive efforts to promote native AVF in patients with marginal
      vessels have increased the rate of primary fistula failure. A non-functioning
      fistula prompts the use of central venous catheter (CVC) that, unlike AVF, has
      been associated with an increased risk of morbidity and mortality among patients
      receiving HD. We believe that successful and timely AVF placement relies on the
      development of a multidisciplinary integrated preoperative program divided into
      five stages: (i) management of patients with advanced chronic kidney disease
      (CKD), (ii) management of preoperative risk factors for AVF failure, (iii)
      planning of native AVF, (iv) assessment of patient eligibility and (v)
      preoperative vascular mapping. Focusing specifically on native AVF, we review
      scientific evidence regarding preoperative management of this vascular access in
      order to favor construction of long-term functioning fistula minimizing
      development of severe complications.

PMID- 29027183
TI  - Actinic cystitis: causes, treatment and experience of a single centre in the last
      five years.
AB  - INTRODUCTION: Actinic cystitis (AC) is the manifestation of symptoms and signs
      following pelvic radiotherapy. Pelvic radiotherapy produces both acute and
      chronic damage and such damage may have a devastating impact on the quality and
      on the amount of life of the patient. OBJECTIVES: To evaluate the number of
      radical cystectomies that have become necessary in the last five years in our
      department for AC after radiation treatment. MATERIALS AND METHODS: From February
      2012 to February 2017, 11 patients underwent "open" cystectomy for AC. All
      patients were studied with radiographic examinations and endoscopy prior to
      surgery. We retrospectively evaluated the type of primitive cancer, the radiation
      dose administered, the time between radiation treatment and cystectomy. We also
      studied the related symptoms that required surgery. RESULTS: The mean age of
      patients at the time of cystectomy was 75 years. In six patients (54.4%)
      radiotherapy was performed for prostate cancer, for rectal cancer in two patients
      (18.1%), and for endometrial cancer in three patients (27.2%). Total radiant dose
      was different in different patients depending on the type and localization of
      cancer. The median time between radiotherapy and cystectomy was 111 months (24
      256 months). All patients had symptoms before surgery. Seven patients (63.3%)
      with gross haematuria were treated with endoscopic clot evacuation and
      fulguration. DISCUSSION: The first approach to patients with AC is often
      supportive care. Surgery remains the most invasive treatment in the management of
      those patients who are not responsive to conservative treatments.

PMID- 29027184
TI  - Low rate of clinically important avascular necrosis of the femoral head after
      Ludloff's procedure.
AB  - INTRODUCTION: Ludloff's procedure for open reduction of congenital dislocation of
      the hip (CDH) is recommended for its minimal tissue damage, but is criticised for
      the risk of late avascular necrosis (AVN) of the femoral head. The aim of present
      study was primarily to assess the risk of late AVN of the femoral head and
      secondly the range of motion (ROM) of the hip and the quality of life in children
      following Ludloff's procedure. METHODS AND MATERIALS: 13 hips in 11 children
      after Ludloff's procedure due to CDH were included retrospectively from 1997 to
      2005 at Aarhus University Hospital. Radiographs were evaluated for the presence
      of AVN of the femoral head and classified according to the Bucholz and Ogden
      classification, with type 2-4 having clinical relevance. A clinical examination
      included range of motion (ROM) and leg length discrepancy (LLD) measurements. The
      HAGOS hip questionnaire evaluated activity, participation and quality of life.
      RESULTS: No severe type 3-4 AVN was observed. 2 type 2 and 5 type 1 were
      observed. AVN was observed in 7 of the 13 operated hips (54%). An 8.6 degrees 
      difference in flexion for unilaterally treated hips was observed (p<0.02). 8 of
      11 patients had minor LLD (range 0.5-2 cm). CONCLUSIONS: Only minor AVN of
      clinical importance was seen after Ludloff's procedure.

PMID- 29027185
TI  - Advanced containment methods for Legg-Calve-Perthes disease: triple pelvic
      osteotomy versus Chiari osteotomy.
AB  - INTRODUCTION: The goal of intervention in Legg-Calve-Perthes disease (LCPD) is to
      prevent femoral head deformation by containing the head within the acetabulum.
      Currently, surgical containment methods are the mainstay of treatment, and pelvic
      osteotomies have been shown to be successful. They include triple pelvic
      osteotomy (TPO), Salter osteotomy, Chiari osteotomy and shelf procedure. The
      purpose of this study was to compare clinical and radiologic results for Chiari
      osteotomy and TPO in LCPD. METHODS: 29 children treated between 1980 and 2010 for
      LCPD in 2 centres were reviewed. 19 underwent TPO, and 10, Chiari osteotomy. Two
      independent observers assessed sequential radiographs and medical data. Each hip
      was preoperatively classed by clinical data, Catteral, Herring and Salter
      Thompson classification, centre-edge angle (CE), and acetabular index (AI). The 2
      groups were first tested for their comparability. After surgery the hips were
      classified by Stulberg classification, CE, AI, Harris Hip Score (HHS) and
      performance of further surgery. Chiari osteotomy and TPO have been secondary
      compared on these data by Wilcoxon test. RESULTS: Average follow-up was 4.2
      years. The 2 groups were comparable before surgery. At first and last follow-up
      examination, statistically significantly superior results in patients with TPO
      regarding Stulberg classification (p = 0.01), AI (p = 0.002), pain (p = 0.02) and
      function (p = 0.01) in the HHS score were found. No differences were noticed
      concerning CE angle. CONCLUSIONS: In our series, TPO provided better radiologic
      and clinical outcomes compared to Chiari osteotomy, specially concerning the
      final Stulberg classification. We concluded that TPO should be preferred when
      indicated.

PMID- 29027186
TI  - Novel technique for intraoperative sciatic nerve assessment in complex primary
      total hip arthroplasty: a pilot study.
AB  - INTRODUCTION: Sciatic nerve injury (SNI) is a potentially devastating
      complication after total hip arthroplasty (THA). Intraoperative neural monitoring
      has been found in several studies to be useful in preventing SNI, but can be
      difficult to implement. In this study, we examine the results of using a handheld
      nerve stimulator for intraoperative sciatic nerve (SN) monitoring during complex
      THA requiring limb lengthening and/or significant manipulation of the SN.
      METHODS: A consecutive series of 11 cases (9 patients, 11 hips) with either
      severe developmental dysplasia of the hip (Crowe 3-4) or other underlying
      conditions requiring complex hip reconstruction involving significant leg
      lengthening and/or nerve manipulation. SN function was monitored intraoperatively
      by obtaining pre- and post-reduction thresholds during component trialing. The
      results of nerve stimulation were then used to influence intraoperative decision
      making. RESULTS: No permanent postoperative SN complications occurred, with an
      average increase of 28.5 mm in limb length, range (6-51 mm). In 2 out of 11
      cases, a change in nerve response was identified after trial reduction, which
      resulted in an alternate surgical plan (femoral shortening osteotomy and
      downsizing femoral head). In the remaining cases, the stimulator demonstrated a
      response consistent with the baseline assessment, assuring that the appropriate
      lengthening was achieved without SNI. 1 patient had a transient motor and sensory
      peroneal nerve palsy, which resolved within 2 weeks. CONCLUSIONS: The
      intraoperative use of a handheld nerve stimulator facilitates surgical decision
      making and can potentially prevent SNI. The real-time assessment of nerve
      function allows immediate corrective action to be taken before nerve injury
      occurs.

PMID- 29027187
TI  - Midterm results of trochanteric flip osteotomy technique for management of
      fractures around the hip.
AB  - INTRODUCTION: In this study, we aimed to investigate safety and efficacy of the
      trochanteric flip osteotomy with surgical hip dislocation technique in selected
      displaced acetabular and femoral head fractures with clinico-radiological outcome
      and potential complications. MATERIALS AND METHODS: We retrospectively reviewed
      32 patients from January 2009 to June 2014. Selected displaced acetabular
      fractures with comminution and/or cranial extension of posterior wall, marginal
      impaction, intraarticular fragment, femoral head fractures and hip fracture
      dislocations were operated by this modified approach of trochanteric flip
      osteotomy and surgical hip dislocation. Patients were evaluated for fracture
      reduction, femoral head viability, trochanteric union, abduction power, and
      functional evaluation was done by Merle d'Aubigne-Postel scoring system. Minimum
      follow-up was 24 months. RESULTS: Reduction was judged to be anatomical in 84.38%
      of cases, and within 1-3 millimetres in 9.38% of cases. All osteotomies healed in
      an anatomical position. Heterotopic ossification was found in 2 patients limited
      to Brooker class I. Osteonecrosis developed in 1 patient. 2 patients developed
      arthritis of the hip as sequelae of poor reduction. Abduction power was MRC 5/5
      in all except in 1 patient (4/5). Mean Merle d'Aubigne-Postel score was 16.18;
      overall good to excellent result was achieved in 87.5% of cases. CONCLUSIONS:
      Trochanteric flip osteotomy with surgical dislocation allows better
      intraarticular assessment, control of intraarticular fragments, assists accurate
      reduction and the fixation of complex acetabular and femoral head fractures,
      without compromising femoral head vascularity and abductor strength. This
      technique has provided excellent midterm results in the management of complex
      injuries around the hip.

PMID- 29027188
TI  - Transfusion rate using intravenous tranexamic acid in hip revision surgery.
AB  - INTRODUCTION: Hip revision surgery is associated with a high probability of the
      necessity for a blood transfusion. Different studies support the use of
      tranexamic acid (TXA) to decrease the rate of transfusions in primary hip
      surgery. Nevertheless, the use of this drug in hip revision surgery has not yet
      been widely accepted. The aim of our study was to establish the rate of blood
      transfusion with and without TXA in hip revision surgery. METHODS: We
      retrospectively studied 125 hip revision surgery patients operated on between
      2011 and 2014. We divided our series into 2 groups: the TXA group with 61
      patients (in which a 1000 mg dose of TXA was used before the skin incision and a
      second identical dose after skin closure) and a control group with 64 patients.
      We analysed the red blood cell (RBC) transfusion rates and their odds risk as
      well as the presence of collateral complications. RESULTS: Average RBC
      transfusion was 2.7 units/patient (range 0-6) in the control group compared to
      1.6 units/patient (range 0-6) in the TXA group. A 90.11% (odds ratio [OR] 0.098;
      confidence interval [CI] 0.02-0.04; p<0.0029) odds risk reduction for transfusion
      of at least 1 unit of erythrocyte blood cell was observed in the TXA group.
      Complications associated with the TXA were similar in both groups.
      INTERPRETATION: The benefits of TXA have been shown in elective hip replacement.
      In this study, TXA proved to be safe and efficacious in reducing the need for
      transfusions following revision total hip arthroplasty.

PMID- 29027189
TI  - Evidence based recommendations for reducing head-neck taper connection fretting
      corrosion in hip replacement prostheses.
AB  - INTRODUCTION: This systematic review seeks to summarise the published studies
      investigating prosthetic design, manufacture and surgical technique's effect on
      fretting corrosion at the head-neck taper connection, and provide clinical
      recommendations to reduce its occurrence. METHODS: PubMed, MEDLINE and EMBASE
      electronic databases were searched using the terms taper, trunnion, cone and head
      neck junction. Articles investigating prosthetic design, manufacture and surgical
      technique's effect on fretting corrosion were retrieved, reviewed and graded
      according to OCEBM levels of evidence and grades of recommendation. RESULTS: The
      initial search yielded 1,224 unique articles, and 91 were included in the
      analysis. CONCLUSIONS: There is fair evidence to recommend against the use of
      high offset femoral heads, larger diameter femoral heads, and to pay particular
      consideration to fretting corrosion's progression with time and risk with heavier
      or more active patients. Particular to metal-on-metal hip prostheses, there is
      fair evidence to recommend positioning the acetabular component to minimise edge
      loading. Particular to metal-on-polyethylene hip prostheses, there is fair
      evidence to recommend the use of ceramic femoral heads, against use of cast
      cobalt alloy femoral heads, and against use of low flexural rigidity femoral
      stems. Evidence related to taper connection design is largely conflicting or
      inconclusive. Head-neck taper connection fretting corrosion is a multifactorial
      problem. Strict adherence to the guidelines presented herein does not eliminate
      the risk. Prosthesis selection is critical, and well-controlled studies to
      identify each design parameter's relative contribution to head-neck taper
      connection fretting corrosion are required.

PMID- 29027190
TI  - Mid-term results of revision total hip arthroplasty with an uncemented modular
      femoral component.
AB  - INTRODUCTION: During revision total hip arthroplasty (THA), the surgeon commonly
      faces deficient proximal femoral bone. In this situation, distal fixation of the
      prosthesis is required. The aim of the current retrospective study is to assess
      the clinical and radiographic mid-term outcome of revision total hip arthroplasty
      using a modular uncemented, tapered, grit-blasted, distal straight stem system.
      METHODS: This retrospective study included 70 femoral revisions that were
      performed in 67 patients using the device of interest. All patients were operated
      on via an extended trochanteric osteotomy. 60 revisions were performed as 1-stage
      (12 infected) and 10 as 2-stage (all infected) revisions. At 3 months
      postoperatively and at final follow-up, patients were assessed radiographically
      for the presence of osteolysis and for distal integration. RESULTS: The mean
      follow-up time was 4.3 (2.0-7.6) years. 4 patients had a removal of at least 1
      prosthetic component. Stem survival for any reason was 92% after 5 years (95%
      confidence interval [CI], 83%-100%). With aseptic loosening of the stem as the
      endpoint of interest, survival after 5 years was 96% (95% CI, 88%-100%). A
      postoperative subsidence rate of 14.7% was found. No perioperative femoral
      fractures were found in the current patient series. CONCLUSIONS: This study
      showed excellent mid-term survival and good clinical and radiographic outcomes in
      patients who had undergone revision THA with a modular uncemented, tapered,
      straight design.

PMID- 29027192
TI  - Hip resurfacing arthroplasty for patients with inflammatory arthritis: a
      systematic review.
AB  - INTRODUCTION: Modern metal-on-metal hip resurfacing arthroplasty has led to
      decreased revision rates and high implant survival rates as compared to prior
      generations of resurfacing. Many of the series that report on resurfacing
      outcomes focus upon patients treated with a diagnosis of osteoarthritis. Patients
      with inflammatory arthritis such as rheumatoid arthritis (RA) and ankylosing
      spondylitis (AS) are also treated in these series, however, their outcomes
      following resurfacing are underreported. The aim of this study was to determine
      complications that may occur following hip resurfacing in patients with
      inflammatory arthritis. A secondary aim was to determine functional outcomes
      following resurfacing. METHODS: A search was performed in MEDLINE (PubMed/OVID),
      Cochrane Library, and Google Scholar. 5 studies met eligibility criteria. This
      review includes 196 hips; 120 had a diagnosis of AS or seronegative
      spondyloarthropathy and 76 had a diagnosis of RA or juvenile RA. 8 revisions were
      reported at a mean time of 64.2 (8.67-275.58) weeks. RESULTS: Femoral neck
      fracture was the most common indication for revision, occurring in 3.06% of all
      hips at 34.5 weeks (16.0-52.0). 2 infections, 2 reports of acetabular
      radiolucency, and no dislocations were reported. The University of California at
      Los Angeles score, Harris Hip Score, and Range of Motion were the most common
      functional outcomes measured, which increased in the majority of studies
      following resurfacing. CONCLUSIONS: Femoral neck fracture was the most common
      reason for revision in patients with inflammatory arthritis following resurfacing
      and there were no dislocations reported. Following resurfacing, these patients
      have improved functional outcomes.

PMID- 29027191
TI  - THA conversion rate comparing decompression alone, with autologous bone graft or
      stem cells in osteonecrosis.
AB  - INTRODUCTION: Core decompression (CD) with or without the addition of autologous
      bone graft (CDBG) is currently the most widely accepted treatment for hip
      osteonecrosis in stages of pre-collapse. The use of bone marrow mesenchymal stem
      cells (CDSC) is emerging as a promising biological alternative. We sought to
      determine the total hip arthroplasty (THA) conversion rate for patients treated
      with CD, CDBG or CDSC. MATERIAL AND METHODS: Between 1996 and 2012, 97 cases were
      evaluated in 72 patients: 47 CD cases, 34 CDGB cases and 16 CDSC cases. The mean
      age was 39 (20-63) years, 25 bilateral, 19 female and 53 male, 14 Ficat 1 and 83
      Ficat 2. Bilateral cases with asymmetric stage and equal treatment were excluded.
      RESULTS: Conversion rate to THA was 44% for the CD group (21/47) at an average of
      77 (24-324) months; 50% for the CDBG group (17/34) at an average of 34 (24-240)
      months and 50% for the CDSC group (8/16) at an average of 48 (24-72) months (p =
      0.619). Log Rank test for survivorship analysis was not significant (p = 0.2011).
      Immunodeficiency or corticosteroid treatment history was associated with 16/47 of
      the CD group, 7/34 in the CDBG group and 1/16 in the CDSC group. Trauma was
      associated with 2/47 of the CD group, 5/34 of the CDBG group and none of the CDSC
      group. Hazard ratio considering risk factors was not significant (p = 0.252).
      CONCLUSIONS: In these series of cases including patients with pre-collapse
      osteonecrosis, we observed non-significant results regarding rate of conversion
      to THA with CD, CDBG or CDSC at an average of 5.5 years.

PMID- 29027193
TI  - Single-center experience with intraoperative extracorporeal membrane oxygenation
      use in lung transplantation.
AB  - BACKGROUND: Studies have shown that survival after lung transplantation is
      impaired if extracorporeal membrane oxygenation (ECMO) support is implemented. We
      investigated the outcome and potential independent risk factors on survival in
      recipients undergoing lung transplantation with intraoperative ECMO support.
      MATERIALS AND METHODS: Medical records of recipients were retrospectively
      evaluated (January 2000-December 2014). Retransplantation and bridge to
      transplantation on ECMO were excluded. Recipients (n = 291) were divided into 2
      groups: those who needed intraoperative ECMO support (Group 1, n = 134) and those
      who did not receive intraoperative ECMO support (Group 2, n = 157). Independent
      risk factors were identified by a stepwise backward regression analysis. RESULTS:
      1-year survival was 84.2% in Group 1 vs. 90.4% in Group 2, and 5-year survival
      was 52.8% in Group 1 vs. 70.5% in Group 2 (p = 0.002). Multivariate analysis
      indicated that recipient age (p = 0.001), renal replacement therapy (p = 0.001)
      and intraoperative ECMO support (p = 0.03) were significant risk factors for
      overall survival. The rate of postoperative early surgical complications was
      comparable between the two groups (p = 0.09). The number of patients requiring
      renal replacement therapy and experiencing late pulmonary complications was
      significantly higher in Group 1 (p = 0.02). CONCLUSIONS: Our data showed that
      lung transplantation with intraoperative ECMO support is associated with poor
      outcomes.

PMID- 29027194
TI  - Predictive Performance of Physiologically Based Pharmacokinetic (PBPK) Modeling
      of Drugs Extensively Metabolized by Major Cytochrome P450s in Children.
AB  - The accuracy of physiologically based pharmacokinetic (PBPK) model prediction in
      children, especially those younger than 2 years old, has not been systematically
      evaluated. The aim of this study was to characterize the pediatric predictive
      performance of the PBPK approach for 10 drugs extensively metabolized by CYP1A2
      (theophylline), CYP2C8 (desloratidine, montelukast), CYP2C9 (diclofenac), CYP2C19
      (esomeprazole, lansoprazole), CYP2D6 (tramadol), and CYP3A4 (itraconazole,
      ondansetron, sufentanil). Model performance in children was evaluated by
      comparing simulated plasma concentration-time profiles with observed clinical
      results for each drug and age group. PBPK models reasonably predicted the
      pharmacokinetics of desloratadine, diclofenac, itraconazole, lansoprazole,
      montelukast, ondansetron, sufentanil, theophylline, and tramadol across all age
      groups. Collectively, 58 out of 67 predictions were within 2-fold and 43 out of
      67 predictions within 1.5-fold of observed values. Developed PBPK models can
      reasonably predict exposure in children age 1 month and older for an array of
      predominantly CYP metabolized drugs.

PMID- 29027196
TI  - Care mapping for the medically complex child.

PMID- 29027195
TI  - TSPYL Family Regulates CYP17A1 and CYP3A4 Expression: Potential Mechanism
      Contributing to Abiraterone Response in Metastatic Castration-Resistant Prostate
      Cancer.
AB  - The testis-specific Y-encoded-like protein (TSPYL) gene family includes TSPYL1 to
      TSPYL6. We previously reported that TSPYL5 regulates cytochrome P450 (CYP) 19A1
      expression. Here we show that TSPYLs, especially TSPYL 1, 2, and 4, can regulate
      the expression of many CYP genes, including CYP17A1, a key enzyme in androgen
      biosynthesis, and CYP3A4, an enzyme that catalyzes the metabolism of abiraterone,
      a CYP17 inhibitor. Furthermore, a common TSPYL1 single nucleotide polymorphism
      (SNP), rs3828743 (G/A) (Pro62Ser), abolishes TSPYL1's ability to suppress CYP3A4
      expression, resulting in reduced abiraterone concentrations and increased cell
      proliferation. Data from a prospective clinical trial of 87 metastatic castration
      resistant prostate cancer patients treated with abiraterone acetate/prednisone
      showed that the variant SNP genotype (A) was significantly associated with worse
      response and progression-free survival. In summary, TSPYL genes are novel CYP
      gene transcription regulators, and genetic alteration within these genes
      significantly influences response to drug therapy through transcriptional
      regulation of CYP450 genes.

PMID- 29027197
TI  - The risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in new users
      of antiepileptic drugs.
AB  - OBJECTIVE: Older antiepileptic drugs (AEDs) are known to cause Stevens-Johnson
      syndrome and toxic epidermal necrolysis (SJS/TEN). However, evidence for newer
      AED is sparse. We quantified risks of SJS/TEN in association with use of all AEDs
      in the United Kingdom. METHODS: In a matched case-control study of 480 previously
      validated SJS/TEN cases (1995-2013) we used conditional logistic regression to
      calculate odds ratios (ORs) with 95% confidence intervals (CIs), and calculated
      absolute risks of SJS/TEN within separate cohorts of new users of 28 AEDs. We
      assessed causality between drugs and SJS/TEN in each exposed case, using an
      adapted version of the algorithm of drug causality for epidermal necrolysis
      (ALDEN) score. RESULTS: We observed a strong association between SJS/TEN and new
      use of carbamazepine (OR 92.57, 95% CI 19.89-infinity), phenytoin (OR 49.96, 95%
      CI 10.13-infinity), and lamotrigine (OR 26.90, 95% CI 4.88-infinity), where
      causality, according to the ALDEN score, was very probable or probable for most
      exposed cases. Absolute risks for SJS/TEN were highest for phenytoin (45.86
      cases/100,000 exposed), lamotrigine (44.17 cases/100,000 exposed), and
      carbamazepine (20.38 cases/100,000 exposed). Despite increased ORs for valproate
      (40,941 exposed), gabapentin (116,037 exposed), pregabalin (59,967 exposed), and
      clobazam (4,300 exposed), ALDEN suggested no causal association. There were no
      observed cases of SJS/TEN among new users of levetiracetam (n = 96,77),
      clonazepam (n = 18,075), or topiramate (n = 11,307). SIGNIFICANCE: The results of
      our study are consistent with those of previous studies of SJS/TEN, which found
      increased risks of SJS/TEN in new use of carbamazepine, phenytoin, and
      lamotrigine. Despite frequent use, no ALDEN-score confirmed cases were observed
      in new users of valproate, gabapentin, pregabalin, levetiracetam, topiramate, or
      clonazepam.

PMID- 29027198
TI  - Shape analysis of spatial relationships between orbito-ocular and endocranial
      structures in modern humans and fossil hominids.
AB  - The orbits and eyes of modern humans are situated directly below the frontal
      lobes and anterior to the temporal lobes. Contiguity between these orbital and
      cerebral elements could generate spatial constraints, and potentially lead to
      deformation of the eye and reduced visual acuity during development. In this
      shape analysis we evaluate whether and to what extent covariation exists between
      ocular morphology and the size and spatial position of the frontal and temporal
      areas in adult modern humans. Magnetic resonance imaging (MRI) was used to
      investigate patterns of variation among the brain and eyes, while computed
      tomography (CT) was used to compare cranial morphology in this anatomical region
      among modern humans, extinct hominids and chimpanzees. Seventeen landmarks and
      semi-landmarks that capture the outline of the eye, frontal lobe, anterior
      fossa/orbital roof and the position of the temporal tips were sampled using
      lateral scout views in two dimensions, after projection of the average grayscale
      values of each hemisphere, with midsagittal and parasagittal elements overlapped
      onto the same plane. MRI results demonstrated that eye position in adult humans
      varies most with regard to its horizontal distance from the temporal lobes and,
      secondly, in its vertical distance from the frontal lobes. Size was mainly found
      to covary with the distance between the eye and temporal lobes. Proximity to
      these cerebral lobes may generate spatial constraints, as some ocular deformation
      was observed. Considering the CT analysis, modern humans vary most with regard to
      the orientation of the orbits, while interspecific variation is mainly associated
      with separation between the orbits and endocranial elements. These findings
      suggest that size and position of the frontal and temporal lobes can affect eye
      and orbit morphology, though potential effects on eye shape require further
      study. In particular, possible effects of these spatial and allometric
      relationships on the eye and vision should be examined using ontogenetic samples,
      vision parameters such as refractive error in diopters, and three-dimensional
      approaches that include measures of extraocular soft tissues within the orbit.

PMID- 29027200
TI  - Do Personality Traits Mediate the Relationship Between Childhood Abuse and
      Migraine? An Exploration of the Relationships in Young Adults Using the Add
      Health Dataset.
AB  - BACKGROUND: Personality traits (especially neuroticism) and childhood
      maltreatment have been independently related to many negative health outcomes
      later in life, including migraine. Studies have also shown the association
      between childhood maltreatment and maladaptive personality traits. The mediating
      role of personality traits on the relationship between childhood maltreatment and
      depression, psychological distress, and alcohol dependence has been extensively
      studied. However, this type of mediation has not been studied in the case of the
      development of migraine. This study investigated (1) the main effects of
      childhood abuse on personality traits, and of personality traits on migraine, and
      (2) the mediating role of neuroticism, on the relationship between childhood
      abuse and migraine in young adults. METHOD: We analyzed retrospective, cross
      sectional data from 13,493 adults aged 24-32 years in Wave 4 of the National
      Longitudinal Survey of Adolescent Health ("Add Health") data set. Participants
      were queried regarding maltreatment (emotional, physical, and sexual) during
      childhood, current Big Five personality traits (using mini International
      Personality Item Pool), current depression (using Center for Epidemiologic
      Studies-Depression Scale), perceived stress (Using Cohen's Perceived Stress
      Scale), and diagnosis of migraine by a health care provider. Linear and logistic
      regressions were used to assess the main effects of childhood maltreatment on the
      five personality traits (openness to experience, conscientiousness, extraversion,
      agreeableness, and neuroticism) and the main effect of the personality traits on
      self-reported provider diagnosis of migraine. A structural equation model (SEM)
      was used to examine the mediating role of neuroticism on the relationship between
      childhood maltreatment and migraine. RESULTS: Linear regression models showed
      that childhood abuse independently predicted increased neuroticism (beta = 0.338,
      SE=+/-0.05, P < .001), and increased openness to experiences (beta = 0.341, SE =
      +/-0.06, P < .001) after adjusting for socio-demographic characteristics, current
      depression, and perceived stress. Logistic regression to examine the main effect
      of personality traits on migraine revealed that only neuroticism had a
      significant effect (OR = 1.07, 95%CI = 1.04-1.10) after controlling for childhood
      abuse, socio-demographic characteristics, current depression, and perceived
      stress. Our regression analyses showed that neuroticism, but not openness to
      experience, was a potential mediator for the relationship between childhood abuse
      and migraine. SEM confirmed significant mediation of the relationship between
      childhood abuse and migraine through neurotic personality traits (goodness of fit
      indices: CFI = 0.992, TLI = 0.979, RMSEA = 0.025), unadjusted for socio
      demographic variables, depression, and stress. In addition to the indirect effect
      (beta = 0.039, P < .01) of childhood abuse on migraine through neuroticism, there
      was also a significant direct effect (beta = 0.143, P < .01) of childhood abuse
      on migraine. After adjusting for socio-demographic variables, other personality
      types, depression, and stress, both the direct effect (beta = 0.127; P < .01) of
      childhood abuse on migraine and the indirect effect (beta = 0.09; P < .01) of
      childhood abuse on migraine through neuroticism were attenuated, but remained
      significant. CONCLUSION: Childhood abuse is associated with personality and
      migraine. An estimated 21% of the total effect of childhood abuse on migraine
      could be explained by mediation through neuroticism in the unadjusted model. In
      the fully adjusted model, an estimated 8.7% of the total effect could be
      explained by mediation, although, self-reported data limit the ability to draw
      firm conclusions.

PMID- 29027199
TI  - Characterization of a mouse model of sickle cell trait: parallels to human trait
      and a novel finding of cutaneous sensitization.
AB  - Sickle cell trait (SCT) has classically been categorized as a benign condition
      except in rare cases or upon exposure to severe physical conditions. However,
      several lines of evidence indicate that individuals with SCT are not always
      asymptomatic, and additional physiological changes and risks may remain
      unexplored. Here, we utilized mice harbouring one copy of normal human beta
      globin and one copy of sickle human beta globin as a model of SCT to assess
      haematological, histopathological and somatosensory outcomes. We observed that
      SCT mice displayed renal and hepatic vascular congestion after exposure to
      hypoxia. Further, we observed that SCT mice displayed increased cold aversion as
      well as mechanical and heat sensitivity, though to a lesser degree than
      homozygous sickle cell disease mice. Notably, mechanical hypersensitivity
      increased following hypoxia and reoxygenation. Overall our findings suggest that
      SCT is not entirely benign, and further assessment of pain and cutaneous
      sensitization is warranted both in animal models and in clinical populations.

PMID- 29027201
TI  - Phototrophic cultivation of NaCl-tolerant mutant of Spirulina platensis for
      enhanced C-phycocyanin production under optimized culture conditions and its
      dynamic modeling.
AB  - Commercial cultivation of Spirulina sp. is highly popular due to the presence of
      high amount of C-phycocyanin (C-PC) and other valuable chemicals like carotenoids
      and gamma-linolenic acid. In this study, the pH and the concentrations of
      nitrogen and carbon source were manipulated to achieve improved cell growth and C
      PC production in NaCl-tolerant mutant of Spirulina platensis. In this study,
      highest C-PC (147 mg . L-1 ) and biomass (2.83 g . L-1 ) production was achieved
      when a NaCl-tolerant mutant of S. platensis was cultivated in a nitrate and
      bicarbonate sufficient medium (40 and 60 mM, respectively) at pH 9.0 under
      phototrophic conditions. Kinetic study of wildtype S. platensis and its NaCl
      tolerant mutant was also done to determine optimum nitrate concentrations for
      maximum growth and C-PC production. Kinetic parameter of inhibition (Haldane
      model) was fitted to the relationship between specific growth rate and substrate
      concentration obtained from the growth curves. Results showed that the maximum
      specific growth rate (MUmax ) for NaCl-tolerant mutant increased by 17.94% as
      compared to its wildtype counterpart, with a slight increase in half-saturation
      constant (Ks ), indicating that this strain could grow well at high concentration
      of NaNO3 . C-PC production rate (Cmax ) in mutant cells increased by 12.2% at
      almost half the value of Ks as compared to its wildtype counterpart. Moreover,
      the inhibition constant (Ki ) value was 207.85% higher in NaCl-tolerant mutant as
      compared to its wildtype strain, suggesting its ability to produce C-PC even at
      high concentrations of NaNO3 .

PMID- 29027202
TI  - A rare vulval manifestation of acrochordons in a young woman.

PMID- 29027203
TI  - Phylogenetically persistent purinergic modulation of central pattern generators
      for breathing in lamprey and mammals.

PMID- 29027204
TI  - Schnitzler syndrome: A rare cause of chronic recalcitrant urticaria successfully
      treated with Anakinra.

PMID- 29027205
TI  - The dilemma of monotherapy or combination therapy in community-acquired
      pneumonia.
AB  - SCOPE: To study the factors associated with mortality in hospitalized patients
      with community-acquired pneumonia treated with monotherapy or combination
      therapy. METHODS: PubMed and Scopus were searched. Patients receiving macrolides,
      beta-lactams and fluoroquinolones, as monotherapy or in combination, were
      included. Meta-analyses and meta-regressions were performed. RESULTS: Fifty
      studies were included. Overall, monotherapy was not associated with higher
      mortality than combination (RR 1.14, 95% CI 0.99-1.32, I2 84%). Monotherapy was
      associated with higher mortality than combination in North American and
      retrospective studies. beta-lactam monotherapy was associated with higher
      mortality than beta-lactam/macrolide combination in the primary (1.32, 1.12-1.56,
      I2 85%) and most sensitivity analyses. There was no difference in mortality
      between fluoroquinolone monotherapy and beta-lactam/macrolide combination (0.98,
      0.78-1.23, I2 73%). In meta-regressions, the moderators that could partially
      explain the observed statistical heterogeneity were the frequency of cancer
      patients (P = .03) and Pneumonia Severity Index score IV (P = .008). CONCLUSION:
      Due to the considerable heterogeneity and inclusion of unadjusted data, it is
      difficult to recommend a specific antibiotic regimen over another. Specific
      antibiotic regimens, study design and the characteristics of the population under
      study seem to influence the reported outcomes.

PMID- 29027206
TI  - Low-grade gastrointestinal lymphoma in dogs: 20 cases (2010 to 2016).
AB  - OBJECTIVES: To report the clinical presentation, treatment and prognosis of dogs
      with low-grade gastrointestinal lymphoma. MATERIALS AND METHODS: Cases were
      solicited from the American College of Veterinary Internal Medicine Oncology
      Diplomate listserv. Medical records of dogs with low-grade gastrointestinal
      lymphoma diagnosed via a combination of histology and immunohistochemistry with
      or without analysis of polymerase chain reaction for antigen receptor
      rearrangement were included. Signalment, clinical signs, diagnostic test results,
      chemotherapy protocol, response to treatment, date of first progression, rescue
      therapies and date and cause of death or last follow-up visit were collected.
      RESULTS: Twenty cases were included. Males and small breed dogs were over
      represented. Frequent clinical signs included weight loss, vomiting and
      diarrhoea. Most lymphomas were T-cell phenotype (95%), and epitheliotropism was
      commonly described (60%). Immunohistochemistry, polymerase chain reaction for
      antigen receptor rearrangement or both were frequently required for definitive
      diagnosis. Two dogs had resection of an intestinal mass, and all dogs were
      treated with chemotherapy; chlorambucil and prednisone were most commonly
      prescribed. Overall response rate was 70%, and median survival time was 424 days
      (95% confidence interval: 105 to 1206 days). CLINICAL SIGNIFICANCE: Low-grade
      gastrointestinal lymphoma appears to be a rare condition in dogs, and treatment
      with chemotherapy results in a high response rate and favourable survival times.
      Further study is needed to determine its prevalence in dogs with chronic
      enteropathies.

PMID- 29027207
TI  - Resource availability for the management of maternal sepsis in Malawi, other low
      income countries, and lower-middle-income countries.
AB  - OBJECTIVE: To assess the availability of key resources for the management of
      maternal sepsis and evaluate the feasibility of implementing the Surviving Sepsis
      Campaign (SSC) recommendations in Malawi and other low-resource settings.
      METHODS: A cross-sectional study was conducted at health facilities in Malawi,
      other low-income countries, and lower-middle-income countries during January
      March 2016. English-speaking healthcare professionals (e.g. doctors, nurses,
      midwives, and administrators) completed a questionnaire/online survey to assess
      the availability of resources for the management of maternal sepsis. RESULTS:
      Healthcare centers (n=23) and hospitals (n=13) in Malawi showed shortages in the
      resources for basic monitoring (always available in 5 [21.7%] and 10 [76.9%]
      facilities, respectively) and basic infrastructure (2 [8.7%] and 7 [53.8%],
      respectively). The availability of antibiotics varied between Malawian healthcare
      centers (9 [39.1%]), Malawian hospitals (8 [61.5%]), hospitals in other low
      income countries (10/17 [58.8%]), and hospitals in lower-middle-income countries
      (39/41 [95.1%]). The percentage of SSC recommendations that could be implemented
      was 33.3% at hospitals in Malawi, 30.3% at hospitals in other low-income
      countries, and 68.2% at hospitals in lower-middle-income countries. CONCLUSION:
      The implementation of existing SSC recommendations is unrealistic in low-income
      countries because of resource limitations. New maternal sepsis care bundles must
      be developed that are applicable to low-resource settings.

PMID- 29027208
TI  - Occurrence of acute renal failure on the same day as immune globulin product
      administrations during 2008 to 2014.
AB  - BACKGROUND: Acute renal failure (ARF) is a rare serious adverse event after
      immune globulin (IG) use. Our large claims-based study evaluated occurrence of
      same-day ARF after administration of different IGs and ascertained potential risk
      factors, during the 2008 to 2014 study period. STUDY DESIGN AND METHODS: A
      retrospective cohort study was conducted using a large commercial administrative
      database. The cohort included individuals exposed to IG products as identified by
      procedure codes. ARF was ascertained using ICD-9-CM diagnoses. Unadjusted same
      day ARF rates (per 1000 persons exposed) were estimated overall and by age, sex,
      and IG products. Regression analyses were conducted to control for confounding
      and assess potential risk factors. RESULTS: Of 20,440 persons exposed, 163 (7.97
      per 1000) had a recorded same-day ARF. The unadjusted nonzero same-day ARF rates
      (per 1000) ranged from 1.92 (95% confidence interval [CI], 0.05-10.69) for
      Hizentra to 16.97 (95% CI, 11.36-24.37) for Privigen and differed by sex. In
      multivariate analyses, compared to Gammagard Liquid, no significantly elevated
      ARF risks were identified with any IGs. A significantly lower odds ratio was
      identified with Gamunex, 0.53 (95% CI, 0.30-0.93). Age 45 and over, prior renal
      impairment, hypertension, and other factors were associated with increased risk
      of same-day ARF. CONCLUSION: The study showed variation in the risk of IG-related
      ARF by age, sex, and IG products. The study results suggest the importance of
      recipient factors, such as older age and underlying health conditions. Variations
      in ARF occurrence may also be explained by product dosage, administration route
      and rate, and manufacturing processes, which warrant further evaluation.

PMID- 29027209
TI  - Heterogeneous distribution of alectinib in neuroblastoma xenografts revealed by
      matrix-assisted laser desorption ionization mass spectrometry imaging: a pilot
      study.
AB  - BACKGROUND AND PURPOSE: The penetration of the anaplastic lymphoma kinase (ALK)
      inhibitor alectinib in neuroblastomas and the relationship between alectinib and
      ALK expression are unknown. The aim of this study was to perform a quantitative
      investigation of the inter- and intra-tumoural distribution of alectinib in
      different neuroblastoma xenograft models using matrix-assisted laser desorption
      ionization MS imaging (MALDI-MSI). EXPERIMENTAL APPROACH: The distribution of
      alectinib in NB1 (ALK amplification) and SK-N-FI (ALK wild-type) xenograft
      tissues was analysed using MALDI-MSI. The abundance of alectinib in tumours and
      intra-tumoural areas was quantified using ion signal intensities from MALDI-MSI
      after normalization by correlation with LC-MS/MS. KEY RESULTS: The distribution
      of alectinib was heterogeneous in neuroblastomas. The penetration of alectinib
      was not significantly different between ALK amplification and ALK wide-type
      tissues using both LC-MS/MS concentrations and MSI intensities. Normalization
      with an internal standard increased the quantitative property of MSI by adjusting
      for the ion suppression effect. The distribution of alectinib in different intra
      tumoural areas can alternatively be quantified from MS images by correlation with
      LC-MS/MS. CONCLUSION AND IMPLICATIONS: The penetration of alectinib into tumour
      tissues may not be homogenous or influenced by ALK expression in the early period
      after single-dose administration. MALDI-MSI may prove to be a valuable
      pharmaceutical method for elucidating the mechanism of action of drugs by
      clarifying their microscopic distribution in heterogeneous tissues.

PMID- 29027211
TI  - Overview: the modulation of ageing through altered proteostasis.

PMID- 29027210
TI  - Oedema-fibrosis in Duchenne Muscular Dystrophy: Role of cardiovascular magnetic
      resonance imaging.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked muscle disorder characterized by
      progressive, irreversible loss of cardiac and skeletal muscular function.
      Muscular enlargement in DMD is attributed to oedema, due to the increased
      cytoplasmic Na+ concentration. The aim of this review was to present the current
      experience and emphasize the role of cardiovascular magnetic resonance (CMR) in
      the diagnosis of this condition. DMD patients' survival depends on ventilatory
      assistance, as respiratory muscle dysfunction was the most common cause of death
      in the past. Currently, due to improved ventilatory assistance, cardiomyopathy
      has become the main cause of death, even though clinically overt heart failure
      may be absent. CMR is the technique of choice to assess the pathophysiologic
      phenomena taking place in DMD, such as myocardial oedema and subepicardial
      fibrosis. The classic index to assess oedema is the T2-weighted short-tau
      inversion recovery (T2w-STIR), as it suppresses the signal from flowing blood and
      resident fat and enhances sensitivity to tissue fluid. Furthermore, CMR is the
      most reliable technique to detect and quantify fibrosis in DMD. Recently, the new
      indices T2, T1 mapping (native and postcontrast) and the extracellular volume
      (ECV) allow a more accurate approach of myocardial oedema and fibrosis. To
      conclude, the assessment of cardiac oedema and subepicardial fibrosis in the
      inferolateral wall of the left heart ventricle are the most important early
      finding in DMD with preserved ventricular function, and CMR, using both the
      classic and the new indices, is the best technique to detect and monitor these
      lesions.

PMID- 29027212
TI  - Complexity of intravenous iron nanoparticle formulations: implications for
      bioequivalence evaluation.
AB  - Intravenous iron formulations are a class of complex drugs that are commonly used
      to treat a wide variety of disease states associated with iron deficiency and
      anemia. Venofer(r) (iron-sucrose) is one of the most frequently used
      formulations, with more than 90% of dialysis patients in the United States
      receiving this formulation. Emerging data from global markets outside the United
      States, where many iron-sucrose similars or copies are available, have shown that
      these formulations may have safety and efficacy profiles that differ from the
      reference listed drug. This may be attributable to uncharacterized differences in
      physicochemical characteristics and/or differences in labile iron release. As
      bioequivalence evaluation guidance evolves, clinicians should be educated on
      these potential clinical issues before a switch to the generic formulation is
      made in the clinical setting.

PMID- 29027213
TI  - Protective effect of metoclopramide against organophosphate-induced apoptosis in
      the murine skin fibroblast L929.
AB  - This study was performed to evaluate the protective efficacy of metoclopramide
      (MCP) against the organophosphates paraoxon (POX)- and malathion (MLT)-induced
      apoptosis in the murine L929 skin fibroblasts. L929 cells were exposed to either
      POX (10 nm) or 1.0 MUm MLT in the absence and presence of increased
      concentrations of MCP. The protective effect of MCP on these organophosphate
      stimulated apoptotic events was evaluated by flow cytometry analysis after
      staining with annexin-V/propidium iodide, processing and activation of the
      executioner caspase-3, cleavage of the poly-ADP ribose polymerase, fragmentation
      of the nucleosomal DNA and disruption of the mitochondrial membrane potential
      (Deltapsi). Our results showed that increased doses of MCP alone (>=10 MUm) did
      not induce apoptosis or activation of caspase-3. Pretreatment of the cells with
      MCP attenuated all the apoptotic events triggered by the organophosphate
      compounds in a dose-dependent manner reaching ~70-80% protection when they were
      preincubated at 1 and 5 MUm of the drug before the addition of POX and MLT,
      respectively. Interestingly, MCP did not offer a significant protective effect
      against the cytotoxicity of tumor necrosis factor-alpha, cisplatinum, etoposide
      or paclitaxel, which stimulate apoptosis by various mechanisms, suggesting that
      the anti-apoptotic effect of the drug is specific to organophosphates. The strong
      and specific anti-apoptotic activity of subclinical doses of MCP against the
      cytotoxicity of organophosphate compounds suggests its potential clinical
      application in treating their poisoning.

PMID- 29027214
TI  - Development of an alternative zebrafish model for drug-induced intestinal
      toxicity.
AB  - An evaluation of intestinal toxicity is important because the mucosal lining of
      the gastrointestinal tract is the first barrier for oral xenobiotics. Until now,
      a rat model has been recommended as the standard intestinal toxicity model and
      the Caco-2 cell line, originated from a human colon adenocarcinoma, has been used
      as an alternative to this model, but there are limitations regarding cost
      effectiveness and the need for mimicry of the human system. In this study, we
      investigated whether zebrafish could be a valid alternative to rats and Caco-2
      cells as an intestinal toxicity model. We focused on intestinal gene expression
      of cytochrome P450 3A65, oxidative stress, apoptosis, inflammation, and
      intestinal function. Reverse transcription-quantitative polymerase chain reaction
      analysis was conducted using three models: zebrafish, Sprague-Dawley rats and
      Caco-2 cells, and the transcript levels and patterns of indicator genes were
      analyzed in conjunction with histopathological changes. Our results suggested
      that representative intestinal toxicants, indomethacin, diclofenac and
      methotrexate, induced significant transcript level changes in marker genes such
      as CYP3A, inducible nitric oxide synthase, heme oxygenase 1, superoxide dismutase
      1, glutathione peroxidase 1, BCL2 associated X, B-cell lymphoma 2, caspase 9,
      tumor protein p53, nuclear factor-kappaB, interleukin-1beta, tumor necrosis
      factor-alphaalpha and toll-like receptor 2 in the zebrafish model as in the rat
      and Caco-2 cells models. These results suggest that zebrafish model is
      sufficiently worth developing as an intestinal toxicity model that can replace or
      compensate the rat model or Caco-2 cell model.

PMID- 29027215
TI  - Death, danger & immunity: Fundamental mechanisms linking pathogenic or iatrogenic
      cell death events to immune responses.

PMID- 29027216
TI  - The long pentraxin PTX3: A prototypical sensor of tissue injury and a regulator
      of homeostasis.
AB  - Tissue damage frequently occurs. The immune system senses it and enforces
      homeostatic responses that lead to regeneration and repair. The synthesis of
      acute phase molecules is emerging as a crucial event in this program. The
      prototypic long pentraxin PTX3 orchestrates the recruitment of leukocytes,
      stabilizes the provisional matrix in order to facilitate leukocyte and stem
      progenitor cells trafficking, promotes swift and safe clearance of dying cells
      and of autoantigens, limiting autoimmunity and protecting the vasculature. These
      non-redundant actions of PTX3 are necessary for the resolution of inflammation.
      Recent studies have highlighted the mechanisms by which PTX3 adapts the functions
      of innate immune cells, orchestrates tissue repair and contributes to select the
      appropriate acquired immune response in various tissues. Conversely, PTX3
      continues to be produced in diseases where the inflammatory response does not
      resolve. It is therefore a valuable biomarker for more precise and personalized
      stratification of patients, often independently predicting clinical evolution and
      outcome. There is strong promise for novel therapies based on understanding the
      mechanisms with which PTX3 plays its homeostatic role, especially in regulating
      leukocyte migration and the resolution of inflammatory processes.

PMID- 29027217
TI  - Danger signals: Chemotherapy enhancers?
AB  - Endogenous danger signals are molecules normally present in a given cell
      compartment that are rapidly released following cell stress and induce immune
      responses. We and others have shown that dying tumor cells treated with some
      chemotherapies are able to induce anticancer immune responses, which rely on
      their release of danger signals such as the nuclear protein HMGB1. DNA can also
      be released from chemotherapy-treated tumor cells, act as a danger signal, and
      boost anticancer immunity. While the immunostimulatory properties of DNA have
      been identified for decades, the recent discovery of a novel family of receptors,
      cytosolic DNA sensors, has provided a novel impetus not only to understand how
      chemotherapy can trigger anticancer immune responses but also to exploit DNA
      derived molecules for therapeutic use. We will here discuss the molecular
      characteristics of endogenous danger signals released from chemotherapy-treated
      tumor cells and focus on the clinical relevance of using these danger signals in
      chemoimmunotherapeutic strategies against cancer.

PMID- 29027218
TI  - Cell death and immunity in cancer: From danger signals to mimicry of pathogen
      defense responses.
AB  - The immunogenicity of cancer cells is an emerging determinant of anti-cancer
      immunotherapy. Beyond developing immunostimulatory regimens like dendritic cell
      based vaccines, immune-checkpoint blockers, and adoptive T-cell transfer,
      investigators are beginning to focus on the immunobiology of dying cancer cells
      and its relevance for the success of anticancer immunotherapies. It is currently
      accepted that cancer cells may die in response to anti-cancer therapies through
      regulated cell death programs, which may either repress or increase their
      immunogenic potential. In particular, the induction of immunogenic cancer cell
      death (ICD), which is hallmarked by the emission of damage-associated molecular
      patterns (DAMPs); molecules analogous to pathogen-associated molecular patterns
      (PAMPs) acting as danger signals/alarmins, is of great relevance in cancer
      therapy. These ICD-associated danger signals favor immunomodulatory responses
      that lead to tumor-associated antigens (TAAs)-directed T-cell immunity, which
      paves way for the removal of residual, treatment-resistant cancer cells. It is
      also emerging that cancer cells succumbing to ICD can orchestrate "altered-self
      mimicry" i.e. mimicry of pathogen defense responses, on the levels of nucleic
      acids and/or chemokines (resulting in type I interferon/IFN responses or pathogen
      response-like neutrophil activity). In this review, we exhaustively describe the
      main molecular, immunological, preclinical, and clinical aspects of
      immunosuppressive cell death or ICD (with respect to apoptosis, necrosis and
      necroptosis). We also provide an extensive historical background of these fields,
      with special attention to the self/non-self and danger models, which have shaped
      the field of cell death immunology.

PMID- 29027220
TI  - Metabolic regulation of macrophage phenotype and function.
AB  - Studies in the last 20 years have given us a remarkable insight into the
      functional and phenotypic diversity of macrophages which reflects their integral
      role in host defence, homeostasis and pathogenesis. Mouse genetics,
      transcriptomic and epigenetic studies have provided an ontogenic and molecular
      perspective to the phenotypic diversity of these cells. Recently, metabolic
      studies have revealed the crucial role of metabolism and metabolites in shaping
      the phenotype and function of macrophages. Evidence pertaining to this aspect
      will be reviewed here.

PMID- 29027221
TI  - Abscopal, immunological effects of radiotherapy: Narrowing the gap between
      clinical and preclinical experiences.
AB  - Radiotherapy-despite being a local therapy that meanwhile is characterized by an
      impressively high degree of spatial accuracy-can stimulate systemic phenomena
      which occasionally lead to regression and rejection of non-irradiated, distant
      tumor lesions. These abscopal effects of local irradiation have been observed in
      sporadic clinical case reports since the beginning of the 20th century, and
      extensive preclinical work has contributed to identify systemic anti-tumor immune
      responses as the underlying driving forces. Although abscopal tumor regression
      still remains a rare event in the radiotherapeutic routine, increasing numbers of
      cases are being reported, particularly since the clinical implementation of
      immune checkpoint inhibiting agents. Accordingly, interests to systematically
      exploit the therapeutic potential of radiotherapy-stimulated systemic responses
      are constantly growing. The present review briefly delineates the history of
      radiotherapy-induced abscopal effects and the activation of systemic anti-tumor
      immune responses by local irradiation. We discuss preclinical and clinical
      reports with specific focus on the corresponding controversies, and we propose
      issues that should be addressed in the future in order to narrow the gap between
      preclinical knowledge and clinical experiences.

PMID- 29027219
TI  - Death begets a new beginning.
AB  - Cell death is a perpetual feature of tissue microenvironments; each day under
      homeostatic conditions, billions of cells die and must be swiftly cleared by
      phagocytes. However, cell death is not limited to this natural turnover-apoptotic
      cell death can be induced by infection, inflammation, or severe tissue injury.
      Phagocytosis of apoptotic cells is thus coupled to specific functions, from the
      induction of growth factors that can stimulate the replacement of dead cells to
      the promotion of tissue repair or tissue remodeling in the affected site. In this
      review, we outline the mechanisms by which phagocytes sense apoptotic cell death
      and discuss how phagocytosis is integrated with environmental cues to drive
      appropriate responses.

PMID- 29027224
TI  - Immunomodulation by ionizing radiation-impact for design of radio-immunotherapies
      and for treatment of inflammatory diseases.
AB  - Ionizing radiation is often regarded as an element of danger. But, danger
      responses on the cellular and molecular level are often beneficial with regard to
      the induction of anti-tumor immunity and for amelioration of inflammation. We
      outline how in dependence of radiation dose and fraction, radiation itself-and
      especially in combination with immune modulators-impacts on the innate and
      adaptive immune system. Focus is set on radiation-induced changes of the tumor
      cell phenotype and the cellular microenvironment including immunogenic cancer
      cell death. Mechanisms how anti-tumor immune responses are triggered by
      radiotherapy in combination with hyperthermia, inhibition of apoptosis, the
      adjuvant AnnexinA5, or vaccination with high hydrostatic pressure-killed
      autologous tumor cells are discussed. Building on this, feasible multimodal radio
      immunotherapy concepts are reviewed including overcoming immune suppression by
      immune checkpoint inhibitors and by targeting TGF-beta. Since radiation-induced
      tissue damage, inflammation, and anti-tumor immune responses are interconnected,
      the impact of lower doses of radiation on amelioration of inflammation is
      outlined. Closely meshed immune monitoring concepts based on the liquid biopsy
      blood are suggested for prognosis and prediction of cancer and non-cancer
      inflammatory diseases. Finally, challenges and visions for the design of cancer
      radio-immunotherapies and for treatment of benign inflammatory diseases are
      given.

PMID- 29027225
TI  - Necroptotic cell death in anti-cancer therapy.
AB  - Necroptosis is one the best-characterized forms of regulated necrosis.
      Necroptosis is mediated by the kinase activities of receptor interacting protein
      kinase-1 and receptor interacting protein kinase-3, which eventually lead to the
      activation of mixed lineage kinase domain-like. Necroptosis is characterized by
      rapid permeabilization of the plasma membrane, which is associated with the
      release of the cell content and subsequent exposure of damage-associated
      molecular patterns (DAMPs) and cytokines/chemokines. This release underlies the
      immunogenic nature of necroptotic cancer cells and their ability to induce
      efficient anti-tumor immunity. Triggering necroptosis has become especially
      important in experimental cancer treatments as an alternative to triggering
      apoptosis because one of the hallmarks of cancer is the blockade or evasion of
      apoptosis. In this review, we discuss recent advances in necroptosis research and
      the functional consequences of necroptotic cancer cell death, with focus on its
      immunogenicity and its role in the activation of anti-tumor immunity. Next, we
      discuss the molecular mechanisms of phosphatidylserine exposure during
      necroptosis and its role in the recognition of necroptotic cells. We also
      highlight the complex role of the necroptotic pathway in tumor promotion and
      suppression and in metastasis. Future studies will show whether necroptosis is
      truly a better strategy to overcome apoptosis resistance and provide the insights
      needed for development of novel treatment strategies for cancer.

PMID- 29027226
TI  - Efferocytosis of dying cells differentially modulate immunological outcomes in
      tumor microenvironment.
AB  - Programmed cell death (apoptosis) is an integral part of tissue homeostasis in
      complex organisms, allowing for tissue turnover, repair, and renewal while
      simultaneously inhibiting the release of self antigens and danger signals from
      apoptotic cell-derived constituents that can result in immune activation,
      inflammation, and autoimmunity. Unlike cells in culture, the physiological fate
      of cells that die by apoptosis in vivo is their rapid recognition and engulfment
      by phagocytic cells (a process called efferocytosis). To this end, apoptotic
      cells express specific eat-me signals, such as externalized phosphatidylserine
      (PS), that are recognized in a specific context by receptors to initiate
      signaling pathways for engulfment. The importance of carefully regulated
      recognition and clearance pathways is evident in the spectrum of inflammatory and
      autoimmune disorders caused by defects in PS receptors and signaling molecules.
      However, in recent years, several additional cell death pathways have emerged,
      including immunogenic cell death, necroptosis, pyroptosis, and netosis that
      interweave different cell death pathways with distinct innate and adaptive
      responses from classical apoptosis that can shape long-term host immunity. In
      this review, we discuss the role of different cell death pathways in terms of
      their immune potential outcomes specifically resulting in specific cell
      corpse/phagocyte interactions (phagocytic synapses) that impinge on host
      immunity, with a main emphasis on tolerance and cancer immunotherapy.

PMID- 29027227
TI  - Missing in action-The meaning of cell death in tissue damage and inflammation.
AB  - Billions of cells die every day in higher organisms as part of the normal process
      of tissue homeostasis. During special conditions like in development, acute
      infections, mechanical injuries, and immunity, cell death is a common denominator
      and it exerts profound effects in the outcome of these scenarios. To prevent the
      accumulation of aged, superfluous, infected, damaged and dead cells, professional
      phagocytes act in a rapid and efficient manner to clear the battle field and
      avoid spread of the destruction. Neutrophils are the most abundant effector
      immune cells that extravasate into tissues and can turn injured tissues into gory
      battle fields. In peace times, neutrophils tend to patrol tissues without
      provoking inflammatory reactions. We discuss in this review actual and forgotten
      knowledge about the meaning of cell death during homeostatic processes and drive
      the attention to the importance of the action of neutrophils during patrolling
      and for the maintenance or recovery of the homeostatic state once the organism
      gets attacked or injured, respectively. In this fashion, we disclose several
      disease conditions that arise as collateral damage of physiological responses to
      death.

PMID- 29027223
TI  - Inflammatory cell death in intestinal pathologies.
AB  - The intestinal tract is a site of intense immune cell activity that is poised to
      mount an effective response against a pathogen and yet maintain tolerance toward
      commensal bacteria and innocuous dietary antigens. The role of cell death in gut
      pathologies is particularly important as the intestinal epithelium undergoes self
      renewal every 4-7 days through a continuous process of cell death and cell
      division. Cell death is also required for removal of infected, damaged, and
      cancerous cells. Certain forms of cell death trigger inflammation through release
      of damage-associated molecular patterns. Further, molecules involved in cell
      death decisions also moonlight as critical nodes in immune signaling. The manner
      of cell death is, therefore, highly instructive of the immunological consequences
      that ensue. Perturbations in cell death pathways can impact the regulation of the
      immune system with deleterious consequences. In this review, we discuss the
      various forms of cell death with a special emphasis on lytic cell death pathways
      of pyroptosis and necroptosis and their implications in inflammation and cancer
      in the gut. Understanding the implications of distinct cell death pathways will
      help in the development of therapeutic interventions in intestinal pathologies.

PMID- 29027228
TI  - High-mobility group box 1 protein orchestrates responses to tissue damage via
      inflammation, innate and adaptive immunity, and tissue repair.
AB  - A single protein, HMGB1, directs the triggering of inflammation, innate and
      adaptive immune responses, and tissue healing after damage. HMGB1 is the best
      characterized damage-associated molecular pattern (DAMP), proteins that are
      normally inside the cell but are released after cell death, and allow the immune
      system to distinguish between antigens that are dangerous or not. Notably, cells
      undergoing severe stress actively secrete HMGB1 via a dedicated secretion
      pathway: HMGB1 is relocated from the nucleus to the cytoplasm and then to
      secretory lysosomes or directly to the extracellular space. Extracellular HMGB1
      (either released or secreted) triggers inflammation and adaptive immunological
      responses by switching among multiple oxidation states, which direct the mutually
      exclusive choices of different binding partners and receptors. Immune cells are
      first recruited to the damaged tissue and then activated; thereafter, HMGB1
      supports tissue repair and healing, by coordinating the switch of macrophages to
      a tissue-healing phenotype, activation and proliferation of stem cells, and
      neoangiogenesis. Inevitably, HMGB1 also orchestrates the support of stressed but
      illegitimate tissues: tumors. Concomitantly, HMGB1 enhances the immunogenicity of
      mutated proteins in the tumor (neoantigens), promoting anti-tumor responses and
      immunological memory. Tweaking the activities of HMGB1 in inflammation, immune
      responses and tissue repair could bring large rewards in the therapy of multiple
      medical conditions, including cancer.

PMID- 29027222
TI  - Alarmins and immunity.
AB  - More than a decade has passed since the conceptualization of the "alarmin"
      hypothesis. The alarmin family has been expanding in terms of both number and the
      concept. It has recently become clear that alarmins play important roles as
      initiators and participants in a diverse range of physiological and
      pathophysiological processes such as host defense, regulation of gene expression,
      cellular homeostasis, wound healing, inflammation, allergy, autoimmunity, and
      oncogenesis. Here, we provide a general view on the participation of alarmins in
      the induction of innate and adaptive immune responses, as well as their
      contribution to tumor immunity.

PMID- 29027229
TI  - Extracellular nucleosides and nucleotides as immunomodulators.
AB  - Some anticancer agents induce immunogenic cell death that is accompanied by the
      emission of danger signals into the tumor microenvironment, thus attracting and
      activating innate immune effectors and finally inducing anticancer immunity. The
      release of extracellular nucleosides such as adenosine triphosphate (ATP) from
      the tumor in response to anticancer therapy plays a pivotal role in the
      attraction of antigen presenting cells and the activation of inflammasome
      mediated proinflammatory cascades. In contrast, the ectonucleotidase-catalyzed
      phosphohydrolysis of nucleotides to nucleosides reduces the extracellular
      availability of nucleotides, hence limiting the recruitment and activation of
      antigen-presenting cells. In addition, the (over-)production of nucleosides
      including adenosine by ectonucleotidases located on cancer cells and regulatory T
      cells can induce immunosuppression, as adenosine directly inhibits the
      proliferation and activation of effector T cells. Here, we discuss the importance
      of death metabolites for immunomodulation in general, and the role of the purine
      nucleotide ATP and its derivative adenosine in particular. In addition, we
      provide an overview on therapeutic interventions that reinstate tumor
      immunogenicity in conditions where nucleotide-dependent immunostimulation is
      obstructed.

PMID- 29027230
TI  - Immunogenic stress and death of cancer cells: Contribution of antigenicity vs
      adjuvanticity to immunosurveillance.
AB  - Cancer cells are subjected to constant selection by the immune system, meaning
      that tumors that become clinically manifest have managed to subvert or hide from
      immunosurveillance. Immune control can be facilitated by induction of autophagy,
      as well as by polyploidization of cancer cells. While autophagy causes the
      release of ATP, a chemotactic signal for myeloid cells, polyploidization can
      trigger endoplasmic reticulum stress with consequent exposure of the "eat-me"
      signal calreticulin on the cell surface, thereby facilitating the transfer of
      tumor antigens into dendritic cells. Hence, both autophagy and polyploidization
      cause the emission of adjuvant signals that ultimately elicit immune control by
      CD8+ T lymphocytes. We investigated the possibility that autophagy and
      polyploidization might also affect the antigenicity of cancer cells by altering
      the immunopeptidome. Mass spectrometry led to the identification of peptides that
      were presented on major histocompatibility complex (MHC) class I molecules in an
      autophagy-dependent fashion or that were specifically exposed on the surface of
      polyploid cells, yet lost upon passage of such cells through immunocompetent (but
      not immunodeficient) mice. However, the preferential recognition of autophagy
      competent and polyploid cells by the innate and cellular immune systems did not
      correlate with the preferential recognition of such peptides in vivo. Moreover,
      vaccination with such peptides was unable to elicit tumor growth-inhibitory
      responses in vivo. We conclude that autophagy and polyploidy increase the
      immunogenicity of cancer cells mostly by affecting their adjuvanticity rather
      than their antigenicity.

PMID- 29027231
TI  - The renaissance of anti-neoplastic immunity from tumor cell demise.
AB  - Cancer therapies can temporarily reduce tumor burdens by inducing malignant cell
      death. However, cancer cure is still far from realization because tumors often
      gain resistance to current treatment and eventually relapse. Accumulating
      evidence suggests that successful cancer interventions require anti-tumor
      immunity. Therapy-induced cell stress responses ultimately result in one or more
      cell death modalities, including apoptosis, autophagy, necroptosis, and
      pyroptosis. These irreversible dying processes are accompanied by active or
      passive release of cell death-associated molecular patterns (CDAMPs), which can
      be sensed by corresponding pattern recognition receptors (PRR) on tumor
      infiltrating immune cells. This crosstalk with the immune system can reawaken
      immune surveillance in the tumor microenvironment (TME). This review focuses on
      immune-modulatory properties of anti-cancer regimens and CDAMP-mediated
      communications between cell stress responses and the immune contexture of TME. In
      addition, we describe how immunogenic cell death can elicit strong and durable
      anti-tumor immune responses.

PMID- 29027234
TI  - Reply to "Comment on 'Dosimetric comparison of stopping power calibration with
      dual-energy CT and single-energy CT in proton therapy treatment planning' [Med.
      Phys. 43(6), 2845-2854 (2016)]".

PMID- 29027233
TI  - Dysregulated cellular functions and cell stress pathways provide critical cues
      for activating and targeting natural killer cells to transformed and infected
      cells.
AB  - Natural killer (NK) cells recognize and kill cancer cells and infected cells by
      engaging cell surface ligands that are induced preferentially or exclusively on
      these cells. These ligands are recognized by activating receptors on NK cells,
      such as NKG2D. In addition to activation by cell surface ligands, the acquisition
      of optimal effector activity by NK cells is driven in vivo by cytokines and other
      signals. This review addresses a developing theme in NK cell biology: that NK
      activating ligands on cells, and the provision of cytokines and other signals
      that drive high effector function in NK cells, are driven by abnormalities that
      arise from transformation or the infected state. The pathways include genomic
      damage, which causes self DNA to be exposed in the cytosol of affected cells,
      where it activates the DNA sensor cGAS. The resulting signaling induces NKG2D
      ligands and also mobilizes NK cell activation. Other key pathways that regulate
      NKG2D ligands include PI-3 kinase activation, histone acetylation, and the
      integrated stress response. This review summarizes the roles of these pathways
      and their relevance in both viral infections and cancer.

PMID- 29027235
TI  - Low-dose CT for the detection and classification of metastatic liver lesions:
      Results of the 2016 Low Dose CT Grand Challenge.
AB  - PURPOSE: Using common datasets, to estimate and compare the diagnostic
      performance of image-based denoising techniques or iterative reconstruction
      algorithms for the task of detecting hepatic metastases. METHODS: Datasets from
      contrast-enhanced CT scans of the liver were provided to participants in an NIH-,
      AAPM- and Mayo Clinic-sponsored Low Dose CT Grand Challenge. Training data
      included full-dose and quarter-dose scans of the ACR CT accreditation phantom and
      10 patient examinations; both images and projections were provided in the
      training data. Projection data were supplied in a vendor-neutral standardized
      format (DICOM-CT-PD). Twenty quarter-dose patient datasets were provided to each
      participant for testing the performance of their technique. Images were provided
      to sites intending to perform denoising in the image domain. Fully preprocessed
      projection data and statistical noise maps were provided to sites intending to
      perform iterative reconstruction. Upon return of the denoised or iteratively
      reconstructed quarter-dose images, randomized, blinded evaluation of the cases
      was performed using a Latin Square study design by 11 senior radiology residents
      or fellows, who marked the locations of identified hepatic metastases. Markings
      were scored against reference locations of clinically or pathologically
      demonstrated metastases to determine a per-lesion normalized score and a per-case
      normalized score (a faculty abdominal radiologist established the reference
      location using clinical and pathological information). Scores increased for
      correct detections; scores decreased for missed or incorrect detections. The
      winner for the competition was the entry that produced the highest total score
      (mean of the per-lesion and per-case normalized score). Reader confidence was
      used to compute a Jackknife alternative free-response receiver operating
      characteristic (JAFROC) figure of merit, which was used for breaking ties.
      RESULTS: 103 participants from 90 sites and 26 countries registered to
      participate. Training data were shared with 77 sites that completed the data
      sharing agreements. Subsequently, 41 sites downloaded the 20 test cases, which
      included only the 25% dose data (CTDIvol = 3.0 +/- 1.8 mGy, SSDE = 3.5 +/- 1.3
      mGy). 22 sites submitted results for evaluation. One site provided binary images
      and one site provided images with severe artifacts; cases from these sites were
      excluded from review and the participants removed from the challenge. The mean
      (range) per-lesion and per-case normalized scores were -24.2% (-75.8%, 3%) and
      47% (10%, 70%), respectively. Compared to reader results for commercially
      reconstructed quarter-dose images with no noise reduction, 11 of the 20 sites
      showed a numeric improvement in the mean JAFROC figure of merit. Notably two
      sites performed comparably to the reader results for full-dose commercial images.
      The study was not designed for these comparisons, so wide confidence intervals
      surrounded these figures of merit and the results should be used only to motivate
      future testing. CONCLUSION: Infrastructure and methodology were developed to
      rapidly estimate observer performance for liver metastasis detection in low-dose
      CT examinations of the liver after either image-based denoising or iterative
      reconstruction. The results demonstrated large differences in detection and
      classification performance between noise reduction methods, although the majority
      of methods provided some improvement in performance relative to the commercial
      quarter-dose images with no noise reduction applied.

PMID- 29027236
TI  - A fast method to emulate an iterative POCS image reconstruction algorithm.
AB  - PURPOSE: Iterative image reconstruction algorithms are commonly used to optimize
      an objective function, especially when the objective function is nonquadratic.
      Generally speaking, the iterative algorithms are computationally inefficient.
      This paper presents a fast algorithm that has one backprojection and no forward
      projection. METHODS: This paper derives a new method to solve an optimization
      problem. The nonquadratic constraint, for example, an edge-preserving denoising
      constraint is implemented as a nonlinear filter. The algorithm is derived based
      on the POCS (projections onto projections onto convex sets) approach. A windowed
      FBP (filtered backprojection) algorithm enforces the data fidelity. An iterative
      procedure, divided into segments, enforces edge-enhancement denoising. Each
      segment performs nonlinear filtering. RESULTS: The derived iterative algorithm is
      computationally efficient. It contains only one backprojection and no forward
      projection. Low-dose CT data are used for algorithm feasibility studies. The
      nonlinearity is implemented as an edge-enhancing noise-smoothing filter.
      CONCLUSIONS: The patient studies results demonstrate its effectiveness in
      processing low-dose x ray CT data. This fast algorithm can be used to replace
      many iterative algorithms.

PMID- 29027237
TI  - Erratum: "A multichannel block-matching denoising algorithm for spectral photon
      counting CT images" [Med. Phys. 44, 2447-2452 (2017)].

PMID- 29027238
TI  - A deep convolutional neural network using directional wavelets for low-dose X-ray
      CT reconstruction.
AB  - PURPOSE: Due to the potential risk of inducing cancer, radiation exposure by X
      ray CT devices should be reduced for routine patient scanning. However, in low
      dose X-ray CT, severe artifacts typically occur due to photon starvation, beam
      hardening, and other causes, all of which decrease the reliability of the
      diagnosis. Thus, a high-quality reconstruction method from low-dose X-ray CT data
      has become a major research topic in the CT community. Conventional model-based
      de-noising approaches are, however, computationally very expensive, and image
      domain de-noising approaches cannot readily remove CT-specific noise patterns. To
      tackle these problems, we want to develop a new low-dose X-ray CT algorithm based
      on a deep-learning approach. METHOD: We propose an algorithm which uses a deep
      convolutional neural network (CNN) which is applied to the wavelet transform
      coefficients of low-dose CT images. More specifically, using a directional
      wavelet transform to extract the directional component of artifacts and exploit
      the intra- and inter- band correlations, our deep network can effectively
      suppress CT-specific noise. In addition, our CNN is designed with a residual
      learning architecture for faster network training and better performance.
      RESULTS: Experimental results confirm that the proposed algorithm effectively
      removes complex noise patterns from CT images derived from a reduced X-ray dose.
      In addition, we show that the wavelet-domain CNN is efficient when used to remove
      noise from low-dose CT compared to existing approaches. Our results were
      rigorously evaluated by several radiologists at the Mayo Clinic and won second
      place at the 2016 "Low-Dose CT Grand Challenge." CONCLUSIONS: To the best of our
      knowledge, this work is the first deep-learning architecture for low-dose CT
      reconstruction which has been rigorously evaluated and proven to be effective. In
      addition, the proposed algorithm, in contrast to existing model-based iterative
      reconstruction (MBIR) methods, has considerable potential to benefit from large
      data sets. Therefore, we believe that the proposed algorithm opens a new
      direction in the area of low-dose CT research.

PMID- 29027232
TI  - Immune recognition of irradiated cancer cells.
AB  - Ionizing irradiation has been extensively employed for the clinical management of
      solid tumors, with therapeutic or palliative intents, for decades. Until
      recently, radiation therapy (RT) was believed to mediate antineoplastic activity
      mostly (if not only) as a consequence of cancer cell-intrinsic effects. Indeed,
      the macromolecular damage imposed to malignant cells by RT initiates one or
      multiple signal transduction cascades that drive a permanent proliferative arrest
      (cellular senescence) or regulated cell death. Both these phenomena show a rather
      linear dose-response correlation. However, RT also mediates consistent
      immunological activity, not only as an "on-target effect" originating within
      irradiated cancer cells, but also as an "off-target effect" depending on the
      interaction between RT and stromal, endothelial, and immune components of the
      tumor microenvironment. Interestingly, the immunological activity of RT does not
      exhibit linear dose-response correlation. Here, we discuss the mechanisms whereby
      RT alters the capacity of the immune system to recognize and eliminate irradiated
      cancer cells, either as an "on-target" or as on "off-target" effect. In
      particular, we discuss the antagonism between the immunostimulatory and
      immunosuppressive effects of RT as we delineate combinatorial strategies to boost
      the former at the expenses of the latter.

PMID- 29027239
TI  - Erratum: "A novel perfused Bloch-McConnell simulator for analyzing the accuracy
      of dynamic hyperpolarized MRS" [Med. Phys. V43, 854-864(2016)].

PMID- 29027240
TI  - Low-dose CT reconstruction using spatially encoded nonlocal penalty.
AB  - PURPOSE: Computed tomography (CT) is one of the most used imaging modalities for
      imaging both symptomatic and asymptomatic patients. However, because of the high
      demand for lower radiation dose during CT scans, the reconstructed image can
      suffer from noise and artifacts due to the trade-off between the image quality
      and the radiation dose. The purpose of this paper is to improve the image quality
      of quarter dose images and to select the best hyperparameters using the regular
      dose image as ground truth. METHODS: We first generated the axially stacked two
      dimensional sinograms from the multislice raw projections with flying focal spots
      using a single slice rebinning method, which is an axially approximate method to
      provide simple implementation and efficient memory usage. To improve the image
      quality, a cost function containing the Poisson log-likelihood and spatially
      encoded nonlocal penalty is proposed. Specifically, an ordered subsets separable
      quadratic surrogates (OS-SQS) method for the log-likelihood is exploited and the
      patch-based similarity constraint with a spatially variant factor is developed to
      reduce the noise significantly while preserving features. Furthermore, we applied
      the Nesterov's momentum method for acceleration and the diminishing number of
      subsets strategy for noise consistency. Fast nonlocal weight calculation is also
      utilized to reduce the computational cost. RESULTS: Datasets given by the Low
      Dose CT Grand Challenge were used for the validation, exploiting the training
      datasets with the regular and quarter dose data. The most important step in this
      paper was to fine-tune the hyperparameters to provide the best image for
      diagnosis. Using the regular dose filtered back-projection (FBP) image as ground
      truth, we could carefully select the hyperparameters by conducting a bias and
      standard deviation study, and we obtained the best images in a fixed number of
      iterations. We demonstrated that the proposed method with well selected
      hyperparameters improved the image quality using quarter dose data. The quarter
      dose proposed method was compared with the regular dose FBP, quarter dose FBP,
      and quarter dose l1 -based 3-D TV method. We confirmed that the quarter dose
      proposed image was comparable to the regular dose FBP image and was better than
      images using other quarter dose methods. The reconstructed test images of the
      accreditation (ACR) CT phantom and 20 patients data were evaluated by
      radiologists at the Mayo clinic, and this method was awarded first place in the
      Low Dose CT Grand Challenge. CONCLUSION: We proposed the iterative CT
      reconstruction method using a spatially encoded nonlocal penalty and ordered
      subsets separable quadratic surrogates with the Nesterov's momentum and
      diminishing number of subsets. The results demonstrated that the proposed method
      with fine-tuned hyperparameters can significantly improve the image quality and
      provide accurate diagnostic features at quarter dose. The performance of the
      proposed method should be further improved for small lesions, and a more thorough
      evaluation using additional clinical data is required in the future.

PMID- 29027241
TI  - Spatial distribution of kidney disease in the contaminated site of Taranto
      (Italy).
AB  - BACKGROUND: Exposure to heavy metals has been associated with kidney disease. We
      investigated the spatial distribution of kidney disease in the industrially
      contaminated site of Taranto. METHODS: Cases were subjects with a first hospital
      discharge diagnosis of kidney disease. Cases affected by specific comorbidities
      were excluded. Standardized Hospitalization Ratios (SHRs) were computed for
      low/high exposure area and for modeled spatial distribution of cadmium and fine
      particulate matter. RESULT: Using the high/low exposure approach, in subjects
      aged 20-59 years residing in the high exposure area a significant excess of
      hospitalization was observed in males and a non-significant excess in females. No
      excesses were observed in subjects aged 60 years and over. The analysis by the
      modeling approach did not show a significant association with the greatest
      pollution impact area. CONCLUSION: Due to the excesses of hospitalization
      observed in the high/low exposure approach, a continuing epidemiological
      surveillance of residents and occupational groups is warranted.

PMID- 29027242
TI  - Optimal dose and duration of amoxicillin-plus-metronidazole as an adjunct to non
      surgical periodontal therapy: A systematic review and meta-analysis of
      randomized, placebo-controlled trials.
AB  - AIM: This systematic review aimed to determine the optimum dose and duration of
      amoxicillin-plus-metronidazole prescribed as an adjunct to non-surgical treatment
      of periodontitis. METHODS: Electronic searching identified 376 records, of which
      18 were eligible blinded, randomized placebo-controlled trials. The primary
      outcomes assessed were periodontal pocket depth and clinical attachment level at
      3 months, and secondary outcomes were adverse events and compliance. Subgroup
      analyses were conducted to compare lower and higher doses, and 7- and 14-day
      courses. RESULTS: Meta-analysis showed a small beneficial effect of adjunctive
      amoxicillin-plus-metronidazole for each primary outcome, but there was <0.1 mm
      variation with antibiotic dose or duration. Risk differences for adverse events
      in the higher dose and longer duration groups were minimally greater (0.04 and
      0.05, respectively), and there was one report of anaphylaxis; 1.3% of patients
      were not fully compliant. CONCLUSION: There was no clinically meaningful
      difference between different doses or duration of amoxicillin-plus-metronidazole
      at 3 months post-treatment. Without compelling evidence to suggest that any one
      regimen performed superiorly, principles of responsible antibiotic use generally
      recommend the highest dose for the shortest duration of time to reduce the risk
      of antibiotic resistance. Therefore, a 7-day regimen of 500/500 mg or 500/400 mg
      of amoxicillin and metronidazole would be most appropriate.

PMID- 29027243
TI  - Phenytoin: its potential as neuroprotective and retinoprotective drug.

PMID- 29027244
TI  - Unmanned aerial vehicles in construction and worker safety.
AB  - Applications of unmanned aerial vehicles (UAVs) for military, recreational,
      public, and commercial uses have expanded significantly in recent years. In the
      construction industry, UAVs are used primarily for monitoring of construction
      workflow and job site logistics, inspecting construction sites to assess
      structural integrity, and for maintenance assessments. As is the case with other
      emerging technologies, occupational safety assessments of UAVs lag behind
      technological advancements. UAVs may create new workplace hazards that need to be
      evaluated and managed to ensure their safe operation around human workers. At the
      same time, UAVs can perform dangerous tasks, thereby improving workplace safety.
      This paper describes the four major uses of UAVs, including their use in
      construction, the potential risks of their use to workers, approaches for risk
      mitigation, and the important role that safety and health professionals can play
      in ensuring safe approaches to the their use in the workplace.

PMID- 29027246
TI  - Medicinal Attributes of Thienopyrimidine Based Scaffold Targeting Tyrosine
      Kinases and Their Potential Anticancer Activities.
AB  - Thienopyrimidines (TP), comprising a thiophene ring fused with pyrimidine, are
      famous bioisosteres to purines, an essential part of the human metabolome. This
      scaffold has become an interesting structural element in the development of
      pharmaceutical compounds, due to their wide spectrum applications as cytotoxic
      agents against different types of human cancer cell lines, cGMP phosphodiesterase
      inhibitors, and anti-viral, anti-inflammatory, and anti-microbial agents. The
      structural similarity of this scaffold with adenine made it an excellent moiety
      to be used in the design of kinase inhibitors. This review focuses on the
      chemistry of thienopyrimidine derivatives, their potential activities against
      various kinases, and their structure-activity relationship studies.

PMID- 29027247
TI  - Wednesday's Meeting Really Is on Friday: A Meta-Analysis and Evaluation of
      Ambiguous Spatiotemporal Language.
AB  - Experimental work has shown that spatial experiences influence spatiotemporal
      metaphor use. In these studies, participants are asked a question that yields
      different responses depending on the metaphor participants use. It has been
      claimed that English speakers are equally likely to respond with either variant
      in the absence of priming. Related studies testing non-spatial experiences
      demonstrate varied results with a wide range of primes. Here, the effects of eye
      movement and stimuli presentation modality on comprehension of this question are
      investigated in different formats. In addition, the results of prior reported
      controls are re-analyzed in a meta-analysis to verify reliable ambiguity of the
      test question. Results suggest that English speakers have a baseline preference
      for the Moving Ego metaphor variant, with a stronger preference in verbal rather
      than written presentation. The findings have implications both for
      (re)interpretation of prior studies' results and future study designs.

PMID- 29027245
TI  - Epac-induced ryanodine receptor type 2 activation inhibits sodium currents in
      atrial and ventricular murine cardiomyocytes.
AB  - Acute RyR2 activation by exchange protein directly activated by cAMP (Epac)
      reversibly perturbs myocyte Ca2+ homeostasis, slows myocardial action potential
      conduction, and exerts pro-arrhythmic effects. Loose patch-clamp studies,
      preserving in vivo extracellular and intracellular conditions, investigated Na+
      current in intact cardiomyocytes in murine atrial and ventricular preparations
      following Epac activation. Depolarising steps to varying test voltages activated
      typical voltage-dependent Na+ currents. Plots of peak current against
      depolarisation from resting potential gave pretreatment maximum atrial and
      ventricular currents of -20.23 +/- 1.48 (17) and -29.8 +/- 2.4 (10) pA/MUm2 (mean
      +/- SEM [n]). Challenge by 8-CPT (1 MUmol/L) reduced these currents to -11.21 +/-
      0.91 (12) (P < .004) and -19.3 +/- 1.6 (11) pA/MUm2 (P < .04) respectively.
      Currents following further addition of the RyR2 inhibitor dantrolene (10 MUmol/L)
      (-19.91 +/- 2.84 (13) and -26.6 +/- 1.7 (17)), and dantrolene whether alone (
      19.53 +/- 1.97 (8) and -27.6 +/- 1.9 (14)) or combined with 8-CPT (-19.93 +/-
      2.59 (12) and -29.9 +/- 2.5(11)), were indistinguishable from pretreatment values
      (all P >> .05). Assessment of the inactivation that followed by applying
      subsequent steps to a fixed voltage 100 mV positive to resting potential gave
      concordant results. Half-maximal inactivation voltages and steepness factors, and
      time constants for Na+ current recovery from inactivation in double-pulse
      experiments, were similar through all the pharmacological conditions.
      Intracellular sharp microelectrode membrane potential recordings in intact
      Langendorff-perfused preparations demonstrated concordant variations in maximum
      rates of atrial and ventricular action potential upstroke, (dV/dt)max . We thus
      demonstrate an acute, reversible, Na+ channel inhibition offering a possible
      mechanism for previously reported pro-arrhythmic slowing of AP propagation
      following modifications of Ca2+ homeostasis, complementing earlier findings from
      chronic alterations in Ca2+ homeostasis in genetically-modified RyR2-P2328S
      hearts.

PMID- 29027248
TI  - Ursodeoxycholic acid protects cardiomyocytes against cobalt chloride induced
      hypoxia by regulating transcriptional mediator of cells stress hypoxia inducible
      factor 1alpha and p53 protein.
AB  - In hepatocytes, ursodeoxycholic acid (UDCA) activates cell signalling pathways
      such as p53, intracellular calcium ([Ca2+ ]i ), and sphingosine-1-phosphate (S1P)
      receptor via Galphai -coupled-receptor. Recently, UDCA has been shown to protect
      the heart against hypoxia-reoxygenation injury. However, it is not clear whether
      UDCA cardioprotection against hypoxia acts through a transcriptional mediator of
      cells stress, HIF-1alpha and p53. Therefore, in here, we aimed to investigate
      whether UDCA could protect cardiomyocytes (CMs) against hypoxia by regulating
      expression of HIF-1alpha, p53, [Ca2+ ]i , and S1P-Galphai -coupled-receptor.
      Cardiomyocytes were isolated from newborn rats (0-2 days), and hypoxia was
      induced by using cobalt chloride (CoCl2 ). Cardiomyocytes were treated with UDCA
      and cotreated with either FTY720 (S1P-receptor agonist) or pertussis toxin (PTX;
      Galphai inhibitor). Cells were subjected for proliferation assay, beating
      frequency, QuantiGene Plex assay, western blot, immunofluorescence, and calcium
      imaging. Our findings showed that UDCA counteracted the effects of CoCl2 on cell
      viability, beating frequency, HIF-1alpha, and p53 protein expression. We found
      that these cardioprotection effects of UDCA were similar to FTY720, S1P agonist.
      Furthermore, we observed that UDCA protects CMs against CoCl2 -induced [Ca2+ ]i
      dynamic alteration. Pharmacological inhibition of the Galphai -sensitive receptor
      did not abolish the cardioprotection of UDCA against CoCl2 detrimental effects,
      except for cell viability and [Ca2+ ]i . Pertussis toxin is partially effective
      in inhibiting UDCA protection against CoCl2 effects on CM cell viability.
      Interestingly, PTX fully inhibits UDCA cardioprotection on CoCl2 -induced [Ca2+
      ]i dynamic changes. We conclude that UDCA cardioprotection against CoCl2 -induced
      hypoxia is similar to FTY720, and its actions are not fully mediated by the
      Galphai -coupled protein sensitive pathways. Ursodeoxycholic acid is the most
      hydrophilic bile acid and is currently used to treat liver diseases. Recently,
      UDCA is shown to have a cardioprotection effects; however, the mechanism of UDCA
      cardioprotection is still poorly understood. The current data generated were the
      first to show that UDCA is able to inhibit the activation of HIF-1alpha and p53
      protein during CoCl2 -induced hypoxia in cardiomyocytes. This study provides an
      insight of UDCA mechanism in protecting cardiomyocytes against hypoxia.

PMID- 29027250
TI  - Revisiting the need for bone marrow examination in chronic myeloid leukemia.

PMID- 29027249
TI  - Development of an LC-MS/MS method for quantification of two isomeric
      phenylpropenes and the application to pharmacokinetic studies in rats.
AB  - Isomers beta-asarone and alpha-asarone have recently been demonstrated to have
      differential pharmacological activities. Here, we report an LC-MS/MS method
      developed using acetonitrile to extract two isomeric phenylpropenes from rat
      plasma. Separation was achieved using a XDB-C18 column (100 * 2.1 mm; i.d., 1.8
      MUm) with a mobile phase of methanol-0.1% formic acid (55:45, v/v) at a flow rate
      of 0.3 mL/min. Calibration curves ranging from 5.20 to 2080 ng/mL for beta
      asarone and from 3.68 to 1470 ng/mL for alpha-asarone were linear (r2  >= 0.9938)
      with the lower limits of quantification being 5.20 and 3.68 ng/mL for both
      isomers. Intravenous administration of beta-asarone (2.22 mg/kg) and alpha
      asarone (2.36 mg/kg) in rats yielded half-lives of 13.40 +/- 4.11 and 28.88 +/-
      7.82 min with clearance values of 0.196 +/- 0.062 mL/min/kg and 0.112 +/- 0.012
      mL/min/kg for beta-asarone and alpha-asarone, respectively.

PMID- 29027251
TI  - New Biguanides as Anti-Diabetic Agents, Part II: Synthesis and Anti-Diabetic
      Properties Evaluation of 1-Arylamidebiguanide Derivatives as Agents of Insulin
      Resistant Type II Diabetes.
AB  - New 1-arylamidebiguanide hydrochloride salts were synthesized via reaction of
      hydrazide derivatives with dicyandiamide in acidic medium. The structure of the
      obtained derivatives was characterized by spectroscopic and elemental analysis
      tools. The anti-diabetic properties of the synthesized compounds were determined.
      Oral treatment of hyperglycemic rats with the synthesized biguanide derivatives
      showed a significant decrease of the elevated glucose in comparison with the anti
      diabetic standard drug, metformin. The effects of the synthesized biguanide
      derivatives on the diabetic properties regarding liver function enzyme activities
      (AST, ALT, and ALP), lipid profiles (TC, TG, and TL), lipid peroxide, and nitrous
      oxide as well as histopathological characteristics were investigated and
      discussed.

PMID- 29027252
TI  - The athlete's hematological response to hypoxia: A meta-analysis on the influence
      of altitude exposure on key biomarkers of erythropoiesis.
AB  - Altitude training is associated with changes in blood markers, which can confound
      results of the Athlete?s Biological Passport (ABP). This meta-analysis aims to
      describe the fluctuations during- and post-altitude in key ABP variables;
      hemoglobin concentration ([Hb]), square-root transformed reticulocyte percentage
      (sqrt(retic%)) and the OFF-score. Individual de-identified raw data were provided
      from 17 studies. Separate linear mixed effects analyses were performed for delta
      values from baseline for [Hb], sqrt(retic%) and OFF-score, by altitude phase
      (during and post). Mixed models were fitted with the hierarchical structure:
      study and subject within study as random effects. Delta values as response
      variables and altitude dose (in kilometer hours; km.hr = altitude (m) / 1000 x
      hours), sex, age, protocol and baseline values as fixed effects. Allowances were
      made for potential autocorrelation. Within two days at natural altitude [Hb]
      rapidly increased. Subsequent delta [Hb] values increased with altitude dose,
      reaching a plateau of 0.94 g/dL [95%CI (0.69, 1.20)] at ~1000 km.hr. Delta
      sqrt(retic%) and OFF-score were the first to identify an erythrocyte response,
      with respective increases and decreases observed within 100 to 200 km.hr. Post
      altitude, [Hb] remained elevated for two weeks. Delta sqrt(retic%) declined below
      baseline, the magnitude of change was dependent on altitude dose. Baseline values
      were a significant covariate (p<0.05). The response to altitude is complex
      resulting in a wide range of individual responses, influenced primarily by
      altitude dose and baseline values. Improved knowledge of the plausible
      hematological variations during- and post-altitude provides fundamental
      information for both the ABP expert and sports physician.

PMID- 29027253
TI  - The nose as a predilection site of pemphigus.

PMID- 29027254
TI  - Lymphoplasmacytoid cytology in plasma cell leukemia.

PMID- 29027256
TI  - Integrated in silico and in vivo approaches to investigate effects of BDE-99
      mediated by the nuclear receptors on developing zebrafish.
AB  - One of the most abundant polybrominated diphenyl ethers (PBDEs) is 2,2',4,4',5
      pentabromodiphenyl ether (BDE-99), which persists and potentially bioaccumulates
      in aquatic wildlife. Previous studies in mammals have shown that BDE-99 affects
      development and disrupts certain endocrine functions through signaling pathways
      mediated by nuclear receptors. However, fewer studies have investigated the
      potential of BDE-99 to interact with nuclear receptors in aquatic vertebrates
      such as fish. In the present study, interactions between BDE-99 and nuclear
      receptors were investigated by in silico and in vivo approaches. This PBDE was
      able to dock into the ligand-binding domain of zebrafish aryl hydrocarbon
      receptor 2 (AhR2) and pregnane X receptor (PXR). It had a significant effect on
      the transcriptional profiles of genes associated with AhR or PXR. Based on the
      developed cytoscape of all zebrafish genes, it was also inferred that AhR and PXR
      could interact via cross-talk. In addition, both the in silico and in vivo
      approaches found that BDE-99 affected peroxisome proliferator-activated receptor
      alpha (PPARalpha), glucocorticoid receptor, and thyroid receptor. Collectively,
      our results demonstrate for the first time detailed in silico evidence that BDE
      99 can bind to and interact with zebrafish AhR and PXR. These findings can be
      used to elaborate the molecular mechanism of BDE-99 and guide more objective
      environmental risk assessments. Environ Toxicol Chem 2018;37:780-787. (c) 2017
      SETAC.

PMID- 29027255
TI  - Tracking capybara (Hydrochoerus hydrochaeris) feces contribution method in
      aquatic environments using sterols.
AB  - The monitoring of fecal contamination (human and animal) is an incessant
      challenge. In this approach, microbiological methods play an important role,
      though with substantial limitations. Organic compounds, such as sterols, are
      often used to trace fecal contamination. Although the fecal sterols profiles of
      some animals are already known, capybara, a typical mammal from South America, is
      a significant contributor to aquatic fecal contamination because of its water
      dependence; and still there is no one way, scientifically speaking, to trace its
      fecal contribution. The aim of the present study was to provide a tool to measure
      the temporal fecal contribution of capybara in aquatic systems. We examined the
      sterol content of capybara feces and compared with another species (sheep, cow,
      horse, pig, hen, duck, cat, dog, opossum, and human). From numerical
      relationships among fecal sterols, 6 ratios were delineated and tested to assess
      their potential to identify the capybara feces contribution in contaminated
      environments. Statistical analysis showed that 3 ratios were able to
      differentiate capybara feces from other sources. Such ratios were applied in
      samples of a sediment core from an urban area in south Brazil with a large
      capybara population. The temporal trend showed a significant contribution of
      capybara feces in the last 100 yr. Environ Toxicol Chem 2018;37:353-361. (c) 2017
      SETAC.

PMID- 29027257
TI  - Review article: consensus statements on therapeutic drug monitoring of anti
      tumour necrosis factor therapy in inflammatory bowel diseases.
AB  - BACKGROUND: Therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD)
      patients receiving anti-tumour necrosis factor (TNF) agents can help optimise
      outcomes. Consensus statements based on current evidence will help the
      development of treatment guidelines. AIM: To develop evidence-based consensus
      statements for TDM-guided anti-TNF therapy in IBD. METHODS: A committee of 25
      Australian and international experts was assembled. The initial draft statements
      were produced following a systematic literature search. A modified Delphi
      technique was used with 3 iterations. Statements were modified according to
      anonymous voting and feedback at each iteration. Statements with 80% agreement
      without or with minor reservation were accepted. RESULTS: 22/24 statements met
      criteria for consensus. For anti-TNF agents, TDM should be performed upon
      treatment failure, following successful induction, when contemplating a drug
      holiday and periodically in clinical remission only when results would change
      management. To achieve clinical remission in luminal IBD, infliximab and
      adalimumab trough concentrations in the range of 3-8 and 5-12 MUg/mL,
      respectively, were deemed appropriate. The range may differ for different disease
      phenotypes or treatment endpoints-such as fistulising disease or to achieve
      mucosal healing. In treatment failure, TDM may identify mechanisms to guide
      subsequent decision-making. In stable clinical response, TDM-guided dosing may
      avoid future relapse. Data indicate drug-tolerant anti-drug antibody assays do
      not offer an advantage over drug-sensitive assays. Further data are required
      prior to recommending TDM for non-anti-TNF biological agents. CONCLUSION:
      Consensus statements support the role of TDM in optimising anti-TNF agents to
      treat IBD, especially in situations of treatment failure.

PMID- 29027258
TI  - Acquired factor XI deficiency and therapeutic plasma exchange.
AB  - Congenital factor XI (FXI) deficiency is associated with a variable bleeding
      phenotype. Recent reports have documented the use of therapeutic plasma exchange
      to rapidly and isovolumetrically increase FXI levels before invasive procedures
      in patients with congenital FXI deficiency. We report a case of acquired FXI
      deficiency in a pregnant woman with lupus. We proved that the inhibitor was an
      IgG, therefore potentially capable of crossing the placenta. While immune
      suppression eliminated detectable circulating inhibitor, the woman's FXI remained
      quite low. A multi-disciplinary team was formed and therapeutic plasma exchange
      with 100% plasma replacement was performed when the patient went into labor, to
      acutely raise her FXI level and remove any potential non-neutralizing inhibitor.
      The mother had a controllable level of bleeding during post-TPE cesarean section;
      the baby had no bleeding and the baby's FXI levels were not overtly abnormal.
      Therapeutic plasma exchange in acquired FXI deficiency (or other acquired
      hemophilias) can both acutely isovolumetrically raise factor levels and remove
      any circulating inhibitor.

PMID- 29027259
TI  - Early urinary biomarkers of renal tubular damage by a high-salt intake
      independent of blood pressure in normotensive rats.
AB  - Dietary sodium intake has been associated with progression to chronic kidney
      disease (CKD) as well as hypertension. A high-salt intake causes renal damage
      independent of hypertension. Because traditional renal biomarkers are
      insensitive, it is difficult to detect renal injury induced by a high-salt
      intake, especially in normotensive patients. Here, we investigated whether newly
      developed renal biomarkers could be detected earlier than traditional biomarkers
      under a high-salt intake, in normotensive rats. Male Wistar Kyoto rats (WKY)
      received a regular (0.8% NaCl) or salt-loaded (2, 4, and 8% NaCl) diet from 9 to
      17 weeks of age. A urine sample was obtained once a week and urinary vanin-1,
      neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1
      (Kim-1) were measured. At 17 weeks of age, 8% salt-loaded WKY showed
      histopathological renal tubular damage and elevated Rac1 activity in renal
      tissues. Although there was no significant increase in serum creatinine, urinary
      albumin, N-acetyl-beta-D-glucosaminidase (NAG), or Kim-1 during the study period
      among the groups, urinary vanin-1 and NGAL significantly increased in 8% salt
      loaded WKY from 10 to 17 weeks of age. These results suggest that urinary vanin-1
      and NGAL, which might be induced by salt per se, are potentially earlier
      biomarkers for renal tubular damage in normotensive rats under a high-salt
      intake.

PMID- 29027260
TI  - Determinants of bed net policy implementation: A case study of Southern Benin.
AB  - BACKGROUND: Malaria is a major global health challenge. This study aims to
      clarify the manner in which contextual factors determine the use and maintenance
      of bed nets and the extent to which malaria prevention policy is responsive to
      them in Southern Benin. METHODS: Semi-structured interviews and direct
      observations were undertaken with 30 pregnant women in the municipality of So-Ava
      from June to August 2015. Key informants in the Ministry of Health and local
      community health workers were also interviewed regarding malaria prevention
      policy formation, and the monitoring and evaluation of bed net interventions,
      respectively. Data were analyzed through categorical content analysis and grouped
      into themes. RESULTS: The majority of pregnant women participants (80%) declared
      non-adherence to instructions for hanging and maintaining insecticide-treated
      nets (ITNs). The distributed bed nets were washed like clothes, which affected
      their bio-efficacy, and were in poor condition (ie, torn or had holes). Multiple
      factors contributed to the poor condition of ITNs: Pregnant women's limited
      understanding of risk including their inability to connect the key environmental
      factors to personal risk, gendered responsibility for installing bed nets, and
      lack of public measures that would enable women to re-treat or access new bed
      nets as needed. Poverty that determined structural aspects of housing such as the
      size and quality of homes and access to bed nets exacerbated the challenges.
      CONCLUSION: Institutionalizing an iterative process of monitoring, review, and
      responsive adaptation throughout the entire policymaking cycle would better
      support malaria preventive policy implementation in Benin.

PMID- 29027261
TI  - Prognostic significance of additional chromosomal abnormalities at the time of
      diagnosis in patients with chronic myeloid leukemia treated with frontline
      tyrosine kinase inhibitors.
AB  - Additional cytogenetic abnormalities (ACA) are considered a high risk feature in
      chronic myeloid leukemia (CML). However, its prognostic significance at the time
      of diagnosis in the setting of new tyrosine kinase inhibitors (TKIs) is less well
      understood. Patients with CML in CP with or without ACA at diagnosis treated with
      frontline TKIs in prospective clinical trials were analyzed for outcomes. Among
      603 patients treated, 29 (5%) had ACA. Patients with ACA included 2 of 72 (2.8%)
      treated with imatinib 400 mg, 9 of 207 (4.3%) with imatinib 800 mg, 10 of 148
      (6.7%) with dasatinib, 6 of 126 (4.7%) with nilotinib, and 2 of 50 (4%) with
      ponatinib. There was a significantly higher rate of complete cytogenetic response
      (CCyR) at 6 months in patients without ACA (P = .02). However cumulative CCyR and
      major molecular response (MMR) rates were not different. Similarly, MR4.0 and
      MR4.5 rates were similar for both groups; two CML-ACA patients maintained MR 4.5
      for at least 2 years. At 5 years, ACA at diagnosis did not significantly impact
      transformation-free, failure-free, event-free, or overall survival expectations.
      Acknowledging small sample size estimates, response rates and survival outcomes
      were comparable in CP with ACA irrespective of whether chromosomal abnormalities
      were "major route" or other. The presence of ACA at diagnosis does not confer
      worse prognosis for patients with CML treated with TKI. Thus, the presence of ACA
      at diagnosis should not alter treatment strategies in these patients.

PMID- 29027263
TI  - On the use of a six-level scale for physical activity.
AB  - The 4-level questionnaire to assess leisure-time physical activity (PA)
      originally described by Saltin and Grimby has been extended to a 6 (or 7)-level
      questionnaire, especially for the elderly or other persons with a low level of
      PA, expanded to include household activities. There are currently two main
      versions, one used in Swedish, Danish, and Norwegian studies, and one with
      further modifications used in Finnish studies. In this review, predictive
      validity for mortality and different aspects of physical performance are
      demonstrated. In a study regarding concurrent validity in one of the Finnish
      versions, significant correlations with accelerometer-based PA variables are
      shown. The scale has been used in a number of studies concerning effects of
      different types of intervention, such as physical training and increased PA, or
      to describe the PA level in the studied cohort. In presenting and analyzing the
      data, different combinations of PA levels have been used. As there are major
      differences between the versions, validity studies cannot easily be transformed
      between them. Thus, it is suggested that a common consensus be reached with
      respect to details of the questionnaire.

PMID- 29027264
TI  - Editorial Comment to Molecular diagnosis of lymph node metastasis in patients
      with upper urinary tract cancer who underwent lymphadenectomy.

PMID- 29027262
TI  - On the origins and industrial applications of Saccharomyces cerevisiae *
      Saccharomyces kudriavzevii hybrids.
AB  - Companies based on alcoholic fermentation products, such as wine, beer and
      biofuels, use yeasts to make their products. Each industrial process utilizes
      different media conditions, which differ in sugar content, the presence of
      inhibitors and fermentation temperature. Saccharomyces cerevisiae has
      traditionally been the main yeast responsible for most fermentation processes.
      However, the market is changing due to consumer demand and external factors such
      as climate change. Some processes, such as biofuel production or winemaking,
      require new yeasts to solve specific challenges, especially those associated with
      sustainability, novel flavours and altered alcohol content. One of the proposed
      solutions is the application of yeast hybrids. The lager beer market has been
      dominated by S. cerevisiae * S. eubayanus hybrids. However, several less
      thoroughly studied hybrids have been isolated from other diverse industrial
      processes. Here we focus on S. cerevisiae * S. kudriavzevii hybrids, which have
      been isolated from diverse industrial conditions that include wine, ale beer,
      cider and dietary supplements. Emerging data suggest an extended and complex
      story of adaptation of these hybrids to traditional industrial conditions. S.
      cerevisiae * S. kudriavzevii hybrids are also being explored for new industrial
      applications, such as biofuels. This review describes the past, present and
      future of S. cerevisiae * S. kudriavzevii hybrids. Copyright (c) 2017 John Wiley
      & Sons, Ltd.

PMID- 29027265
TI  - Shared and task-specific muscle synergies of Nordic walking and conventional
      walking.
AB  - Nordic walking is a form of walking that includes a poling action, and therefore
      an additional subtask, with respect to conventional walking. The aim of this
      study was to assess whether Nordic walking required a task-specific muscle
      coordination with respect to conventional walking. We compared the
      electromyographic (EMG) activity of 15 upper- and lower-limb muscles of 9 Nordic
      walking instructors, while executing Nordic walking and conventional walking at
      1.3 ms-1 on a treadmill. Non-negative matrix factorization method was applied to
      identify muscle synergies, representing the spatial and temporal organization of
      muscle coordination. The number of muscle synergies was not different between
      Nordic walking (5.2 +/- 0.4) and conventional walking (5.0 +/- 0.7, P = .423).
      Five muscle synergies accounted for 91.2 +/- 1.1% and 92.9 +/- 1.2% of total EMG
      variance in Nordic walking and conventional walking, respectively. Similarity and
      cross-reconstruction analyses showed that 4 muscle synergies, mainly involving
      lower-limb and trunk muscles, are shared between Nordic walking and conventional
      walking. One synergy acting during upper limb propulsion is specific to Nordic
      walking, modifying the spatial organization and the magnitude of activation of
      upper limb muscles compared to conventional walking. The inclusion of the poling
      action in Nordic walking does not increase the complexity of movement control and
      does not change the coordination of lower limb muscles. This makes Nordic walking
      a physical activity suitable also for people with low motor skill.

PMID- 29027266
TI  - Reliable and sensitive physical testing of elite trapeze sailors.
AB  - It was investigated whether a newly developed discipline-specific test for elite
      level trapeze sailors is reliable and sensitive. Furthermore, the physical
      demands of trapeze sailing were examined. In part 1, 9 national team athletes
      were accustomed to a simulated sailing test, which subsequently was completed on
      4 occasions to determine test reliability and sensitivity to manipulations in
      body weight. Rope-pulling mean power output (MPO), oxygen consumption (VO2 ),
      heart rate (HR), and blood lactate values were acquired in all trials. In part 2,
      6 sailors completed on-water racing with concurrent measurements of VO2 , HR, and
      blood lactate. VO2max was determined during an incremental treadmill running
      test. Typical error, minimal difference, and ICC for average MPO in the test were
      1.3%, 1.7%, and 0.99%, respectively. Adding 4 kg of external body weight caused a
      decrease in average MPO (270 +/- 45W vs 265 +/- 45W, P < .05) and an increase in
      VO2 (2.44 +/- 0.23 L.min-1 vs 2.55 +/- 0.26 L.min-1 , P < .01). VO2 , HR, and
      blood lactate during on-water sailing were 54.5% +/- 7.2% VO2max , 75.1% +/- 3.1%
      HRmax , and 5.8 +/- 2.7 mmol.L-1 , respectively. However, VO2 and HR were
      substantially higher for periods of the race as peak values were 83.5% +/- 11.4%
      and 89.9% +/- 1.7% of max, respectively. In conclusion, the present test is
      reliable and sensitive, thus providing a sailing-specific alternative to
      traditional physical testing of elite trapeze sailors. Additionally, on-water
      racing requires moderate aerobic energy production, although oxygen consumption
      can approach maximal levels for short periods of time.

PMID- 29027267
TI  - Percutaneous repair of severe mitral valve regurgitation secondary to chordae
      rupture in octogenarians using MitraClip.
AB  - OBJECTIVES: The aim of this study was to assess feasibility and clinical
      effectiveness of the MitraClip device in octogenarians suffering from severe
      mitral valve regurgitation due to chordae rupture. BACKGROUND: The MitraClip
      procedure is a suitable technique in high-risk surgical patients to achieve safe
      and effective percutaneous repair of mitral valve regurgitation. Octogenarians
      show cumulative risk and social aspects hindering mitral valve surgery. No data
      exists regarding the use of the MitraClip device in high-risk octogenarians
      suffering from mitral valve chordae rupture. METHODS: Between October 2009 and
      March 2017 98 high-risk octogenarians (society of thoracic surgeons score [STS]:
      9.7% +/- 0.8) with mitral valve prolapse and consecutively chordae rupture were
      treated with the MitraClip after interdisciplinary discussion. RESULTS:
      Successful mitral valve repair was achieved in 91% of the octogenarians. Repair
      of the mitral valve caused immediate and significant reduction of dyspnoea (NYHA
      class: 3.5 +/- 0.4 vs 2.0 +/- 0.3; P < 0.001), cardiac reverse remodeling (LVESD:
      39 +/- 0.8 vs 35 +/- 0.8; P < 0.01) and amelioration of cardiac biomarkers
      (NTproBNP (4884 +/- 52  ng/L vs 2473 +/- 210 ng/L; P < 0.05,). Effects were
      stable over the 12 months observation period. None of our patients died
      intraprocedurally. CONCLUSIONS: Percutaneous repair of chordae rupture is
      feasible and safe in high-risk octogenarians. The MitraClip should be considered
      to repair severe mitral valve regurgitation due to mitral valve chordae rupture
      in high-risk octogenarians after interdisciplinary discussion even facing a
      challenging anatomy.

PMID- 29027268
TI  - Emergency thoracic aortic stent grafting for aortoesophageal fistula in advanced
      esophageal cancer.

PMID- 29027269
TI  - Partial nephrectomy for small children: Robot-assisted versus open surgery.
AB  - OBJECTIVES: To compare the outcomes of robot-assisted heminephrectomy for duplex
      kidney in children with those of open heminephrectomy. METHODS: The present
      retrospective multicentric analysis reviewed the records of robot-assisted versus
      open heminephrectomy carried out for duplex kidney in children from 2007 to 2014.
      Demographic data, weight, surgical time, hospital stay, complications and outcome
      were recorded. Follow up was based on a clinical review, renal sonography and
      dimercaptosuccinic acid renal scintigraphy. RESULTS: A total of 15 patients
      underwent robot-assisted heminephrectomy, and 13 patients underwent
      retroperitoneal heminephrectomy by open approach. All patients weighed <15 kg.
      The mean age at the time of surgery was 20.2 months (range 7-39 months) in the
      robotic group, and 18.4 months (range 6-41 months) in the open group. The mean
      hospital stay was statistically longer for the open surgery group (6.3 days,
      range 5-8 days vs 3.4 days, range 1-7 days; P < 0.001). Regarding postoperative
      pain control, total morphine equivalent intake was statistically greater for the
      open group (0.52 mg/kg/day vs 1.08 mg/kg/day; P < 0.001). No patient lost the
      remaining healthy moiety. There was no significant difference in terms of
      operating time, complication rate or renal outcomes. CONCLUSIONS: Robot-assisted
      heminephrectomy in small children seems to offer comparable renal outcomes with
      those of its standard open surgery counterpart. Specific technical adjustments
      are necessary, which typically increase the set-up time.

PMID- 29027271
TI  - Surgical treatment of coronary artery aneurysms.
AB  - INTRODUCTION: Coronary artery aneurysms (CAA) are rare. We present our experience
      with the surgical treatment of patients with CAAs. METHODS: Between March 2000
      and October 2016, 15 patients with CAA underwent surgery. RESULTS: Mean age of
      patients was 60 +/- 16 years and 47% (n = 7) were male. Kawasaki syndrome was
      present in two (13%) patients and 7% (n = 1) patients had Marfan syndrome.
      Isolated CAAs were found in 73% (n = 11) and involvement of multiple vessels was
      present in 27% (n = 4) of patients. Coronary arteries (CA) affected by aneurysms
      were: 19% (n = 4) left main stem, 33% (n = 7) left anterior descending, 14% (n =
      3) left circumflex, and 33% (n = 7) right coronary artery. The majority of
      patients (93%, n = 14) were operated on pump with a mean cross-clamp time of 51
      +/- 23 min. 53% (n = 8) of patients received total arterial CA bypass grafting,
      while the remaining patients (47%, n = 7) received venous +/- internal thoracic
      artery grafts. Resection/ligation of CAA was performed in 27% (n = 4) of
      patients. In-hospital mortality was 0% (n = 0). Follow-up was complete for 100%
      of patients and comprised a total of 80 patient-years. During follow-up, only one
      patient (7%) required re-intervention. CONCLUSION: Surgical treatment of CAA has
      good short- and long-term results.

PMID- 29027272
TI  - MoS2 @HKUST-1 Flower-Like Nanohybrids for Efficient Hydrogen Evolution Reactions.
AB  - A novel MoS2 -based flower-like nanohybrid for hydrogen evolution was fabricated
      through coating the Cu-containing metal-organic framework (HKUST-1) onto MoS2
      nanosheets. It is the first time that MoS2 @HKUST-1 nanohybrids have been
      reported for the enhanced electrochemical performance of HER. The morphologies
      and components of the MoS2 @HKUST-1 flower-like nanohybrids were characterized by
      scanning electron microscopy, X-ray diffraction analysis and Fourier transform
      infrared spectroscopy. Compared with pure MoS2 , the MoS2 @HKUST-1 hybrids
      exhibit enhanced performance on hydrogen evolution reaction with an onset
      potential of -99 mV, a smaller Tafel slope of 69 mV dec-1 , and a Faradaic
      efficiency of nearly 100 %. The MoS2 @HKUST-1 flower-like nanohybrids exhibit
      excellent stability in acidic media. This design opens new possibilities to
      effectively synthesize non-noble metal catalysts with high performance for the
      hydrogen evolution reaction (HER).

PMID- 29027270
TI  - The yerba mate intake has a neutral effect on bone: A case-control study in
      postmenopausal women.
AB  - Nutritional factors have been associated with osteoporosis and fractures. The
      intake of coffee may increase the risk of fracture whereas the intake of black
      and green tea is associated with its reduction. Recently, consumption of yerba
      mate was associated with increased bone mineral density in postmenopausal women.
      Nonetheless, its influence on fracture is not known. The aim of this study was to
      evaluate the effect of yerba mate tea intake on fractures, bone markers, calcium
      homeostasis, and oxidative stress in postmenopausal women. A case-control study
      was carried out in South Brazil, 46 women with fractures and 49 controls
      completed the study. There was no significant difference between the frequency of
      fractures in women who drank mate tea and women who did not (48.3% vs. 48.5%, p =
      .99). Moreover, there was no significant difference concerning the serum levels
      of total calcium, phosphorus, PTH, vitamin D, P1NP, and CTX in the subjects with
      the history of yerba mate use when compared to controls. Higher serum levels of
      NOx were found in women who drank the yerba mate infusion. In conclusion, the
      yerba mate intake is not associated with fracture, and it appears to have a
      neutral effect on the bone metabolism.

PMID- 29027273
TI  - Molecular diagnosis of lymph node metastasis in patients with upper urinary tract
      cancer who underwent lymphadenectomy.
AB  - OBJECTIVES: To determine the significance of molecular diagnosis of lymph node
      metastasis using quantitative reverse transcription polymerase chain reaction in
      patients with upper urinary tract urothelial cancer. METHODS: A total of 51
      patients with upper urinary tract urothelial cancer who underwent extended
      lymphadenectomy were included in the present study. Retrieved lymph nodes from
      each patient were divided into two parts. One part was assessed by quantitative
      reverse transcription polymerase chain reaction assay for molecular staging,
      whereas the other one was assessed by routine histopathological examination. Four
      kinds of molecules (FXYD3, KRT19, KRT20 and UPK2) were selected as markers to
      detect urothelial cancer cells. RESULTS: The average number of retrieved lymph
      nodes was 18.3. As UPK2 showed the best discrimination ability among four
      markers, the patients were classified in three categories according to UPK2
      expression: N(+)PCR(+) for patients who had lymph node metastasis by routine
      pathological diagnosis as well as quantitative reverse transcription polymerase
      chain reaction (n = 4); N(-)PCR(+) for patients who had lymph node metastasis by
      polymerase chain reaction but not by routine pathological diagnosis (n = 7); and
      N(-)PCR(-) for patients who showed no lymph node metastasis not only by routine
      pathological diagnosis but also by polymerase chain reaction (n = 40). The
      prognosis of the N(-)PCR(+) group was better than that of the N(+)PCR(+) group,
      and similar to that of the N(-)PCR(-) group. CONCLUSIONS: Quantitative reverse
      transcription polymerase chain reaction could detect micrometastasis in patients
      with upper urinary tract urothelial cancer. However, the prognosis of patients
      with micrometastasis is better than patients with pathologically metastasized
      lymph nodes, and similar to patients without micrometastasis.

PMID- 29027274
TI  - Comparative Oral Absorption of Curcumin in a Natural Turmeric Matrix with Two
      Other Curcumin Formulations: An Open-label Parallel-arm Study.
AB  - Curcuminoids are the major bioactive molecules in turmeric, and poor
      bioavailability deters them from being the major components of many health and
      wellness applications. This study was conducted to assess the bioavailability of
      a completely natural turmeric matrix formulation (CNTMF) and compare its
      bioavailability with two other commercially available formulations, namely,
      curcumin with volatile oil (volatile oil formulation) and curcumin with
      phospholipids and cellulose (phospholipid formulation) in healthy human adult
      male subjects (15 each group) under fasting conditions. Each formulation was
      administrated orally as a single 500-mg dose in capsule form, and blood samples
      were analyzed by liquid chromatography mass spectrometry at various time
      intervals up to 24 h. The ingestion of the CNTMF was very well absorbed and
      resulted in a mean curcuminoids plasma Cmax of 170.14 ng/mL (Tmax  = 4 h)
      compared with 47.54 ng/mL and 69.63 ng/mL for the volatile oil (Tmax  = 3 h) and
      phospholipid (Tmax  = 2.25 h) formulations, respectively. The extent of
      absorption of total curcuminoids in the blood for the CNTMF was 6* greater than
      volatile oil formulation and 5* greater than phospholipids formulation. The
      results of this study indicate that curcumin in a natural turmeric matrix
      exhibited greater bioavailability than the two comparator products. Copyright (c)
      2017 John Wiley & Sons, Ltd.

PMID- 29027275
TI  - Multifaceted Supramolecular Interactions from C-Methylresorcin[4]arene Lead to an
      Enhancement in In Vitro Antibacterial Activity of Gatifloxacin.
AB  - Mimicking the antibacterial activity of polyphenols in synthetic systems is an
      attractive approach for the development of new active pharmaceutical ingredients.
      Resorcinarenes represent a class of polyphenols, which have been exploited for
      decades for their attractive chemical scaffold suitable for forming host-guest
      complexes with hydrophobic guest molecules. However, the polyphenolic character
      of resorcinarenes, which could be a potential asset to the pharmaceutical
      industry, have been least exploited. The present work represents an unprecedented
      interplay of antimicrobial activity of resorcinarene together with its ability to
      interact chemically with an antibacterial drug gatifloxacin, improving the
      overall antibacterial activity. The chemistry and the clinical activities
      involved in this study were investigated simultaneously by spectroscopic
      techniques, as well as by in vitro measurement of antibacterial activity toward
      two human bacterial pathogens, a Gram-positive pathogen Staphylococcus aureus and
      a Gram-negative lung pathogen Legionella pneumophila. The initial positive result
      obtained from this study could revolutionize the use of synthetically modifiable
      resorcinarenes and their analogues in fine tuning the clinical behavior of drugs.

PMID- 29027276
TI  - Natural medicines for acute renal failure: A review.
AB  - Acute renal failure (ARF) is a life-threating disease with high mortality
      percentage. Two important mechanisms of ARF are inflammation and oxidative
      stress. Plants are rich source of antioxidant compounds and have a strong anti
      inflammatory activity, so they may be useful for the treatment of ARF. Some
      herbal medicines are effective against different models of experimentally induced
      ARF such as cisplatin, gentamicin, glycerol, and ischemia-reperfusion injury.
      Some of these plants such as ginseng, black seed, ginger, garlic, grape,
      pomegranate, saffron, and green tea are so famous and are effective against
      various models of ARF. However, we found several articles examining the
      effectiveness of different plants for treating ARF. In the current article, we
      discussed plants and natural products that are effective in the treatment of ARF.

PMID- 29027277
TI  - Relativistic DFT Calculations of Hyperfine Coupling Constants in 5d Hexafluorido
      Complexes: [ReF6 ]2- and [IrF6 ]2.
AB  - The performance of relativistic density functional theory (DFT) methods has been
      investigated for the calculation of the recently measured hyperfine coupling
      constants of hexafluorido complexes [ReF6 ]2- and [IrF6 ]2- . Three relativistic
      methods were employed at the DFT level of theory: the 2-component zeroth-order
      regular approximation (ZORA) method, in which the spin-orbit coupling was treated
      either variationally (EV ZORA) or as a perturbation (LR ZORA), and the 4
      component Dirac-Kohn-Sham (DKS) method. The dependence of the results on the
      basis set and the choice of exchange-correlation functional was studied.
      Furthermore, the effect of varying the amount of Hartree-Fock exchange in the
      hybrid functionals was investigated. The LR ZORA and DKS methods combined with
      DFT led to very similar deviations (about 20 %) from the experimental values for
      the coupling constant of complex [ReF6 ]2- by using hybrid functionals. However,
      none of the methods were able to reproduce the large anisotropy of the hyperfine
      coupling tensor of complex [ReF6 ]2- . For [IrF6 ]2- , the EV ZORA and DKS
      methods reproduced the experimental tensor components with deviations of ~10 and
      ~5 % for the hybrid functionals, whereas the LR ZORA method predicted the
      coupling constant to be around one order of magnitude too large owing to the
      combination of large spin-orbit coupling and very low excitation energies.

PMID- 29027278
TI  - Current Status of Herbal Drug Standards in the Indian Pharmacopoeia.
AB  - The benefits of herbal drugs were well understood way back. They have been used
      for the promotion of health and medical purposes - in disease conditions. It is a
      conventional belief that herbal drugs have no side effects, are cheaper and
      locally available. Among Indian systems of medicines, herbs/herbal formulations
      are used to a larger extent. The quality control of the marketed herbs/herbal
      formulations is important for acquiring optimum therapeutic benefit as well as
      for expanding global outreach. Therefore, herbal drug standards are important.
      Reference standards, the Indian Pharmacopoeia Reference Substances especially the
      botanical reference substances and the phytochemical reference substances are
      required for comparison of quality of herbal drugs. The Indian Pharmacopoeia
      Commission has initiated the process of providing Indian Pharmacopoeia Reference
      Substances to the stakeholders. Therefore, this article provides an overview of
      the history and the status of herbal drug standards in the current and
      forthcoming issues of Indian Pharmacopoeia. In Indian Pharmacopeia, efforts have
      been made for the harmonization of standards with international counterparts
      wherever possible. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 29027279
TI  - Long non-coding RNA PVT1: Emerging biomarker in digestive system cancer.
AB  - The digestive system cancers are leading cause of cancer-related death worldwide,
      and have high risks of morbidity and mortality. More and more long non-coding
      RNAs (lncRNAs) have been studied to be abnormally expressed in cancers and play a
      key role in the process of digestive system tumour progression. Plasmacytoma
      variant translocation 1 (PVT1) seems fairly novel. Since 1984, PVT1 was
      identified to be an activator of MYC in mice. Its role in human tumour initiation
      and progression has long been a subject of interest. The expression of PVT1 is
      elevated in digestive system cancers and correlates with poor prognosis. In this
      review, we illustrate the various functions of PVT1 during the different stages
      in the complex process of digestive system tumours (including oesophageal cancer,
      gastric cancer, colorectal cancer, hepatocellular carcinoma and pancreatic
      cancer). The growing evidence shows the involvement of PVT1 in both proliferation
      and differentiation process in addition to its involvement in epithelial to
      mesenchymal transition (EMT). These findings lead us to conclude that PVT1
      promotes proliferation, survival, invasion, metastasis and drug resistance in
      digestive system cancer cells. We will also discuss PVT1's potential in diagnosis
      and treatment target of digestive system cancer. There was a great probability
      PVT1 could be a novel biomarker in screening tumours, prognosis biomarkers and
      future targeted therapy to improve the survival rate in cancer patients.

PMID- 29027280
TI  - Versatile Tailoring of NH2 -Containing Metal-Organic Frameworks with Paddle-Wheel
      Units.
AB  - An amine-containing non-interpenetrating pillar-layer framework, [Zn2
      (dbtcb)(L1)]?x solvent (1), has been synthesized from Zn(NO3 )2 and the ligands
      1,4-dibromo-2,3,5,6-tetrakis(4-carboxyphenyl)benzene (H4 DBTCB) and 2,5-bis(4
      pyridyl)aniline (L1). The [Zn2 (COO)4 ] secondary building units (SBUs) are
      bridged by DBTCB to form two-dimensional layers that are linked by L1 ligands
      acting as pillars to form a three-dimensional network. This NH2 -containing
      framework can undergo versatile tailoring through post-synthetic covalent
      modification, solvent-assisted linker exchange (SALE), and single-crystal-to
      single-crystal (SC-SC) transmetalation reactions. Acetamide-functionalized [Zn2
      (L2)(dbtcb)]?xsolvent (2) could be obtained by direct synthesis from Zn(NO3 )2 ,
      N-acetyl-2,5-bis(4-pyridyl)aniline (L2) and H4 DBTCB. Importantly, compound 1
      with pure NH2 ligands as pillars could be obtained by SALE of 2 with L1 in DMSO
      solution. The transmetalation reactions of 1 with CuII , NiII , and CoII were
      studied; inductively coupled plasma-atomic emission (ICP) analysis revealed that
      1 underwent almost complete SC-SC transmetalation with CuII within 30 h, whereas
      with NiII and CoII only 70 and 80 % substitutions were achieved.
      Photoluminescence studies revealed that 1 and 2 display yellow-green and UV
      emission, respectively, under a UV lamp. Furthermore, the photoluminescent
      properties could be tuned by introducing mixed pillar amino ligands L1 and L2
      into the MOF to produce multivariate (MTV) MOF 3 displaying overall orange
      emission.

PMID- 29027281
TI  - A New Member of the Inverted Cucurbit[n]uril Family.
AB  - A new inverted cucurbituril, namely inverted hexamethylcucurbit[3,3]uril (iMe6
      Q[3,3]), has been isolated and characterized. It incorporates a single inverted
      un-substituted glycoluril unit oriented towards the interior of the cavity, shows
      good solubility in water and organic solvents (DMSO), and exhibits different
      selectivity for guests to those of iQ[6] and other known Q[6]s.

PMID- 29027282
TI  - Oestrogen retains human periodontal ligament stem cells stemness in long-term
      culture.
AB  - OBJECTIVES: During long-term culture, loss of stemness is observed which greatly
      restricts the application of human periodontal ligament stem cells (hPDLSCs) in
      tissue regeneration. Oestrogen (E2) was found to significantly enhance the
      proliferation and osteogenic differentiation capacity in mesenchymal stem cells.
      Therefore, in this study, we investigated effects of E2 on hPDLSCs stemness in
      long-term culture. MATERIALS AND METHODS: Effects of E2 on hPDLSCs stemness were
      systematically evaluated. To characterize underlying the mechanisms, its effects
      on PI3K/AKT signalling pathway were determined. RESULTS: Our results showed that
      E2 was able to enhance the proliferation, modify cell cycle, up-regulate stemness
      related genes expression, promote osteogenic differentiation and elevate the
      positive rate of CD146 and STRO-1 over 10 passages in hPDLSCs. Importantly,
      PI3K/AKT signing pathway might play a role in these effects. CONCLUSIONS: These
      findings suggest that E2 retains hPDLSCs stemness in long-term culture, which
      might enhance its application in tissue engineering.

PMID- 29027283
TI  - Does managing the consumption of people with severe alcohol dependence reduce
      harm? A comparison of participants in six Canadian managed alcohol programs with
      locally recruited controls.
AB  - INTRODUCTION AND AIMS: Managed alcohol programs (MAP) are intended for people
      with severe alcohol-related problems and unstable housing. We investigated
      whether MAP participation was associated with changes in drinking patterns and
      related harms. DESIGN AND METHODS: One hundred and seventy-five MAP participants
      from five Canadian cities (Hamilton, Ottawa, Toronto, Thunder Bay and Vancouver)
      and 189 same-city controls were assessed for alcohol consumption, health, safety
      and harm outcomes. Length of stay in a MAP was investigated as a predictor of
      drinking patterns, non-beverage alcohol consumption and related harms.
      Statistical controls were included for housing stability, age, gender, ethnic
      background and city of residence. Negative binomial regression and logistic
      regression models were used. RESULTS: Recently admitted MAP participants (<=2
      months) and controls were both high consumers of alcohol, predominantly male, of
      similar ethnic background, similarly represented across the five cities and
      equally alcohol dependent (mean Severity of Alcohol Dependence Questionnaire =
      29.7 and 31.4). After controlling for ethnicity, age, sex, city and housing
      stability, long-term MAP residents (>2 months) drank significantly more days
      (+5.5) but 7.1 standard drinks fewer per drinking day than did controls over the
      last 30 days. Long-term MAP residents reported significantly fewer alcohol
      related harms in the domains of health, safety, social, legal and withdrawal.
      DISCUSSION AND CONCLUSIONS: Participation in a MAP was associated with more
      frequent drinking at lower quantities per day. Participation was associated with
      reduced alcohol-related harms over the past 30 days. Future analyses will examine
      outcomes longitudinally through follow-up interviews, police and health care
      records.

PMID- 29027284
TI  - Polydopamine Particles Reinforced Poly(vinyl alcohol) Hydrogel with NIR Light
      Triggered Shape Memory and Self-Healing Capability.
AB  - This study focuses on developing a facile approach to prepare biocompatible
      poly(vinyl alcohol) (PVA) composite hydrogels containing polydopamine particles
      (PDAPs) with ultrafast near-infrared (NIR) light-triggered shape memory and self
      healing capability. The PVA-PDAPs composite hydrogels with excellent mechanical
      properties can be achieved after freezing/thawing treatment, and the formation of
      physically cross-linked networks from the hydrogen bonding (H-bonding) between
      PVA and PDAPs. Due to the excellent photothermal effect of polydopamine, the
      composited hydrogel can achieve rapid shape recovery and efficient self-healing
      properties under NIR light exposure in a short time. With the excellent shape
      memory performance, good biocompatibility, and self-healing property, this
      hydrogel should have great potential in biomedical fields such as tissue
      engineering, arthrodial cartilage, and artificial skin.

PMID- 29027285
TI  - Subtle Deregulation of the Wnt-Signaling Pathway Through Loss of Apc2 Reduces the
      Fitness of Intestinal Stem Cells.
AB  - The importance of the Wnt-signaling pathway on the regulation and maintenance of
      the intestinal stem cell (ISC) population is well recognized. However, our
      current knowledge base is founded on models using systems of gross deregulation
      of the Wnt-signaling pathway. Given the importance of this signaling pathway on
      intestinal homeostasis, there is a need to explore the role of more subtle
      alterations in Wnt-signaling levels within this tissue. Herein, we have used a
      model of Apc2 loss to meet this aim. Apc2 is a homolog of Apc which can also form
      a destruction complex capable of binding beta-catenin, albeit less efficiently
      than Apc. We show that systemic loss of Apc2 results in an increase in the number
      of cells displaying nuclear beta-catenin at the base of the intestinal crypt.
      This subsequently impacts the expression levels of several ISC markers and the
      fitness of ISCs as assessed by organoid formation efficiency. This work provides
      the first evidence that the function and fitness of ISCs can be altered by even
      minor misregulation of the Wnt-signaling pathway. Our data highlights the
      importance of correct maintenance of this crucial signaling pathway in the
      maintenance and function of the ISC population. Stem Cells 2018;36:114-122.

PMID- 29027287
TI  - Role of the Diphosphine Chelate in Emissive, Charge-Neutral Iridium(III)
      Complexes.
AB  - A class of neutral tris-bidentate IrIII metal complexes incorporating a
      diphosphine as a chelate is prepared and characterized here for the first time.
      Treatment of [Ir(dppBz)(tht)Cl3 ] (1, dppBz=1,2-bis(diphenylphosphino)benzene,
      tht=tetrahydrothiophene) with fppzH (3-trifluoromethyl-5-(2'-pyridyl)-1H
      pyrazole) afforded the dichloride complexes, trans-(Cl,Cl)[Ir(dppBz)(fppz)Cl2 ]
      (2) and cis-(Cl,Cl)[Ir(dppBz)(fppz)Cl2 ] (3). The reaction of 3 with the
      dianionic chelate precursor, 5,5'-di(trifluoromethyl)-3,3'-bipyrazole (bipzH2 )
      or 5,5'-(1-methylethylidene)-bis(3-trifluoromethyl-1H-pyrazole) (mepzH2 ), in DMF
      gave the tris-bidentate complex [Ir(dppBz)(fppz)(bipz)] (4) or
      [Ir(dppBz)(fppz)(mepz)] (5), respectively. In contrast, a hydride complex
      [Ir(dppBz)(fppz)(bipzH)H] (6) was isolated instead of 4 in protic solvent,
      namely: diethylene glycol monomethyl ether (DGME). All complexes 2-6 are
      luminescent in powder form and thin films where the dichlorides (2, 3) emit with
      maxima at 590-627 nm (orange) and quantum yields (QYs) up to 90 % whereas the
      tris-bidentate (4, 5) and hydride (6) complexes emit at 455-458 nm (blue) with
      QYs up to 70 %. Hybrid (time-dependent) DFT calculations showed considerable
      metal-to-ligand charge transfer contribution to the orange-emitting 2 and 3 but
      substantial ligand-centered 3 pi-pi* transition character in the blue-emitting 4
      6. The dppBz does not participate in the radiative transitions in 4-6, but it
      provides the rigidity and steric bulk needed to promote the luminescence by
      suppressing the self-quenching in the solid state. Fabrication of an organic
      light-emitting diode (OLED) with dopant 5 gave a deep-blue CIE chromaticity of
      (0.16, 0.15). Superior blue emitters, which are vital in OLED applications, may
      be found in other neutral IrIII complexes containing phosphine chelates.

PMID- 29027286
TI  - Investigating the bifunctionality of cyclizing and "classical" 5-aminolevulinate
      synthases.
AB  - The precursor to all tetrapyrroles is 5-aminolevulinic acid, which is made either
      via the condensation of glycine and succinyl-CoA catalyzed by an ALA synthase
      (the C4 or Shemin pathway) or by a pathway that uses glutamyl-tRNA as a precursor
      and involves other enzymes (the C5 pathway). Certain ALA synthases also catalyze
      the cyclization of ALA-CoA to form 2-amino-3-hydroxycyclopent-2-en-1-one.
      Organisms with synthases that possess this second activity nevertheless rely upon
      the C5 pathway to supply ALA for tetrapyrrole biosynthesis. The C5 N units are
      components of a variety of secondary metabolites. Here, we show that an ALA
      synthase used exclusively for tetrapyrrole biosynthesis is also capable of
      catalyzing the cyclization reaction, albeit at much lower efficiency than the
      dedicated cyclases. Two absolutely conserved serines present in all known ALA-CoA
      cyclases are threonines in all known ALA synthases, suggesting they could be
      important in distinguishing the functions of these enzymes. We found that
      purified mutant proteins having single and double substitutions of the conserved
      residues are not improved in their respective alternate activities; rather, they
      are worse. Protein structural modeling and amino acid sequence alignments were
      explored within the context of what is known about the reaction mechanisms of
      these two different types of enzymes to consider what other features are
      important for the two activities.

PMID- 29027288
TI  - CXXC5 expression in prostate cancer: implications for cancer progression.
AB  - Identification of genes specifically deregulated in prostate adenocarcinoma may
      lead to discovery of new oncogenes/tumour suppressors with clinical relevance for
      diagnosis, prognosis and/or therapy. CXXC5 is a gene encoding a retinoid
      inducible nuclear factor, whose overexpression in breast tumours, metastatic
      malignant melanomas and papillary thyroid carcinoma has been recently reported.
      We previously found differential expression of CXXC5 transcripts in metastatic
      prostate cancer cell lines of both rat and human origin. However, knowledge on
      the expression of this gene in benign or malignant human prostate tissue is
      lacking. The aim of this study was to determine the mRNA and protein expression
      pattern of CXXC5 in human benign prostate tissue, proliferative inflammatory
      atrophy, high-grade prostatic intra-epithelial neoplasia and prostate cancer,
      using qPCR, chromogenic in situ hybridization and immunohistochemistry. Our
      results showed that protein levels determined by immunohistochemistry were in
      agreement with transcript levels observed by chromogenic in situ hybridization.
      CXXC5 mRNA and protein expressions were significantly higher in prostate cancer,
      high-grade prostatic intra-epithelial neoplasia, and proliferative inflammatory
      atrophy, compared to benign prostate tissue. Significantly, within the same
      tissue specimens, CXXC5 staining was stronger in malignant acini than in matched
      adjacent, benign acini; immunostaining for this protein was mainly localized to
      the nucleus of benign epithelial cells and both the nucleus and cytoplasm of
      malignant epithelial cells. Our findings suggest that CXXC5 may play a role in
      the process of prostate carcinogenesis. Additional studies are required to
      determine the biological and clinical significance of CXXC5 in prostate cancer
      development and/or progression.

PMID- 29027290
TI  - Pertuzumab and trastuzumab infusion related cytokine release syndrome in a
      chemotherapy naive patient with metastatic breast cancer.
AB  - Pertuzumab is a monoclonal antibody that targets and down regulates HER-2/neu
      expression in ductal breast tumors. Other HER-2/neu monoclonal antibodies,
      particularly trastuzumab, have been implicated to induce infusion related
      reactions such as cytokine release syndrome (CRS). Here, we report a case of
      pertuzumab associated CRS prior to infusion of trastuzumab which warranted
      hospitalization for symptom management.

PMID- 29027289
TI  - Polychlorinated dibenzo-p-dioxins and dibenzofurans levels in piglet liver with
      various diseases.
AB  - This study deals with the levels of toxic polychlorinated dibenzo-p-dioxin and
      furan congeners (PCDD/Fs) in the livers of piglets affected by infectious
      diseases using isotope dilution high-resolution gas chromatography/high
      resolution mass spectrometry (HRGC/HRMS). Seventeen toxic congeners in the liver
      samples infected with bacterial and viral diseases were compared. For porcine
      reproductive and respiratory syndrome virus (PRRSV) samples, the North American-
      and European-type PRRS diseases were observed. This study shows that there are
      significantly different levels of PCDD/Fs, present, which vary according to the
      types of diseases as evidenced by our analysis of the piglet liver samples.

PMID- 29027291
TI  - Being a modern paediatric surgeon.

PMID- 29027292
TI  - Strontium isotope measurement of basaltic glasses by laser ablation multiple
      collector inductively coupled plasma mass spectrometry based on a linear
      relationship between analytical bias and Rb/Sr ratios.
AB  - RATIONALE: In situ strontium (Sr) isotope analysis of geological samples by laser
      ablation multiple collector inductively coupled plasma mass spectrometry (LA-MC
      ICP-MS) provides useful information about magma mixing, crustal contamination and
      crystal residence time. Without chemical separation, during Sr isotope analysis
      with laser ablation, many kinds of interference ions (such as Rb+ and Kr+ ) are
      on the Sr isotope spectrum. Most previous in situ Sr isotope studies only focused
      on Sr-enriched minerals (e.g. plagioclase, calcite). Here we established a simple
      method for in situ Sr isotope analysis of basaltic glass with Rb/Sr ratio less
      than 0.14 by LA-MC-ICP-MS. METHODS: Seven Faraday cups, on a Neptune Plus MC-ICP
      MS instrument, were used to receive the signals on m/z 82, 83, 84, 85, 86, 87 and
      88 simultaneously for the Sr isotope analysis of basaltic glass. The isobaric
      interference of 87 Rb was corrected by the peak stripping method. The
      instrumental mass fractionation of 87 Sr/86 Sr was corrected to 86 Sr/88 Sr =
      0.1194 with an exponential law. Finally, the residual analytical biases of 87
      Sr/86 Sr were corrected with a relationship between the deviation of 87 Sr/86 Sr
      from the reference values and the measured 87 Rb/86 Sr. The validity of the
      protocol present here was demonstrated by measuring the Sr isotopes of four
      basaltic glasses, a plagioclase crystal and a piece of modern coral. RESULTS: The
      measured 87 Sr/86 Sr ratios of all these samples agree within 100 ppm with the
      reference values. In addition, the Sr isotopes of olivine-hosted melt inclusions
      from the Emeishan large igneous province (LIP) were measured to show the
      application of our method to real geological samples. CONCLUSIONS: A simple but
      accurate approach for in situ Sr isotope measurement by LA-MC-ICP-MS has been
      established, which should greatly facilitate the wider application of in situ Sr
      isotope geochemistry, especially to volcanic rock studies.

PMID- 29027293
TI  - Determination of chemical identity and occupancy from experimental density maps.
AB  - Three basic electronic properties of molecules, electron density (ED), charge
      density (CD), and electrostatic potentials (ESP), are dependent on both atomic
      mobility and occupancy of components in the molecules. Small protein subunits may
      bind large macromolecular complexes with a reduced occupancy or an increased
      atomic mobility or both due to affinity-based functional regulation, and so may
      substrates, products, cofactors, ions or solvent molecule to the active sites of
      enzymes. A quantitative theory is presented in this study that describes the
      dependence of atomic functions on atomic B-factor in Fourier transforms of the
      corresponding maps. An application of this theory is described to an experimental
      ED map at 1.73-A resolution, and to an experimental CD map at 2.2-A resolution.
      All the three density functions are linearly proportional to occupancy when the
      structure factor F(000) term of Fourier transforms of experimental density maps
      is included. Upon application of this theory to both experimental CD and ESP maps
      recently reported for photosystem II-light harvesting complex II supercomplex at
      3.2-A resolution, the occupancy of two extrinsic protein subunits PsbQ and PsbP
      is determined to be 20.4 +/- 0.2%, and the negative mean ESP value of vitreous
      ice displaced by the supercomplex on electron scattering path is estimated to be
      3% of the mean ESP value of protein alpha-helices.

PMID- 29027294
TI  - Classification of self-injurious behaviour across the continuum of relative
      environmental-biological influence.
AB  - Self-injurious behaviour (SIB) is generally considered to be the product of
      interactions between dysfunction stemming from the primary developmental
      disability and experiences that occasion and reinforce SIB. As a result of these
      complex interactions, SIB presents as a heterogeneous problem. Recent research
      delineating subtypes of SIB that are nonsocially mediated, including one that is
      amenable to change and one that is highly invariant, enables classification of
      SIB across a broader continuum of relative environmental-biological influence.
      Directly examining how the functional classes of SIB differ has the potential to
      structure research, will improve our understanding this problem, and lead to more
      targeted behavioural and pharmacological interventions. Recognising that SIB is
      not a single entity but is composed of distinct functional classes would better
      align research with conceptual models that view SIB as the product of
      interactions between environmental and biological variables.

PMID- 29027295
TI  - Progression of late postoperative atrial fibrillation in patients with tetralogy
      of Fallot.
AB  - INTRODUCTION: ToF patients are at risk for ventricular deterioration at a
      relatively young age, which can be aggravated by AF development. Therefore,
      knowledge on AF development and its timespan of progression is essential to guide
      treatment strategies for AF. OBJECTIVE: We examined late postoperative AF onset
      and progression in ToF patients during long-term follow-up after ToF correction.
      In addition, coexistence of AF with regular supraventricular tachyarrhythmias
      (SVT) and ventricular tachyarrhythmias (VTA) was analyzed. METHODS AND RESULTS:
      ToF patients (N  =  29) with AF after ToF correction referred to the
      electrophysiology department between 2000 and 2015 were included. All available
      rhythm registrations were reviewed for AF, regular SVT, and VTA. AF progression
      was defined as transition from paroxysmal AF to (longstanding)
      persistent/permanent AF or from (longstanding) persistent AF to permanent AF. At
      the age of 44 +/- 12 years, ToF patients presented with paroxysmal (N  =  14,
      48%), persistent (N  =  13, 45%) or permanent AF (N  =  2, 7%). Age of AF
      development was similar among patients who either underwent initial shunt
      creation (N  =  15, 45 +/- 11 [25-57] years) or primary total ToF correction (N 
      =  14, 43 +/- 13 [26-66] years) (P  =  0.785). AF coexisted with regular SVT (N 
      =  18, 62%) and VTA (N  =  13, 45%). Progression of AF occurred in 11 patients
      (38%) within 5 +/- 5 years after AF onset despite antiarrhythmic drug class II
      (AAD, P  =  0.052) or III (P  =  0.587) usage. CONCLUSIONS: AF in our ToF
      population developed at a young age and showed rapid progression. Rhythm control
      by pharmacological therapy was ineffective in preventing AF progression.

PMID- 29027297
TI  - Factors associated with ambulatory care sensitive emergency department visits for
      South Carolina Medicaid members with intellectual disability.
AB  - INTRODUCTION: Ambulatory care sensitive conditions (ACSCs) can be seen as failure
      of access or management in primary care settings. Identifying factors associated
      with ACSCs for individuals with an Intellectual Disability (ID) provide insight
      into potential interventions. METHOD: To assess the association between emergency
      department (ED) ACSC visits and a number of demographic and health
      characteristics of South Carolina Medicaid members with ID. A retrospective
      cohort of adults with ID was followed from 2001 to 2011. Using ICD-9-CM codes,
      four ID subgroups, totalling 14 650 members, were studied. RESULTS: There were
      106 919 ED visits, with 21 214 visits (19.8%) classified as ACSC. Of those, 82.9%
      were treated and released from EDs with costs averaging $578 per visit. People
      with mild and unspecified ID averaged greater than one ED visit per member year.
      Those with Down syndrome and other genetic cause ID had the lowest rates of ED
      visits but the highest percentage of ACSC ED visits that resulted in inpatient
      hospitalisation (26.6% vs. an average of 16.8% for other subgroups). When
      compared with other residential types, those residing at home with no health
      support services had the highest ED visit rate and were most likely to be
      discharged back to the community following an ED visit (85.2%). Adults residing
      in a nursing home had lower rates of ED visits but were most likely to be
      admitted to the hospital (38.9%) following an ED visit. Epilepsy and convulsions
      were the leading cause (29.6%) of ACSC ED visits across all subgroups and
      residential settings. CONCLUSION: Prevention of ACSC ED visits may be possible by
      targeting adults with ID who live at home without health support services.

PMID- 29027296
TI  - Monomer Protonation-Dependent Surface Polymerization to Achieve One-Step Grafting
      Cross-Linked Poly(4-Vinylpyridine) Onto Core-Shell Fe3 O4 @SiO2 Nanoparticles.
AB  - Functional polymer-grafting silica nanoparticles hold great promise in diverse
      applications such as molecule recognition, drug delivery, and heterogeneous
      catalysis due to high density and uniform distribution of functional groups and
      their tunable spatial distance. However, conventional grafting methods from
      monomers mainly consist of one or more extra surface modification steps and a
      subsequent surface polymerization step. A monomer protonation-dependent surface
      polymerization strategy is proposed to achieve one-step uniform surface grafting
      of cross-linked poly(4-vinylpyridine) (P4VP) onto core-shell Fe3 O4 @SiO2
      nanostructures. At an approximate pH, partially protonated 4VP sites in aqueous
      solution can be strongly adsorbed onto deprotonated silanol groups (?Si?O- ) onto
      Fe3 O4 @SiO2 nanospheres to ensure prior polymerization of these protonated 4VP
      sites exclusively onto Fe3 O4 @SiO2 nanoparticles and subsequent polymerization
      of other 4VP and divinylbenzene monomers harvested by these protonated 4VP
      monomers onto Fe3 O4 @SiO2 nanoparticles, thereby achieving direct grafting of
      cross-linked P4VP macromolecules onto Fe3 O4 @SiO2 nanoparticles.

PMID- 29027298
TI  - Identification of gelsemine metabolites in rat liver S9 by high-performance
      liquid chromatography/quadrupole-time-of-flight mass spectrometry.
AB  - RATIONALE: Gelsemine has been extensively studied because of its anti-tumor,
      immunomodulatory, insecticidal itching and other significant effects. However,
      limited information on the pharmacokinetics and metabolism of gelsemine has been
      reported. Therefore, the purpose of the present study was to investigate the in
      vitro metabolism of gelsemine in rat liver S9 by using rapid and accurate high
      performance liquid chromatography/ quadrupole-time-of-flight mass spectrometry
      (HPLC/QqTOF-MS). METHODS: The incubation mixture was processed with 15%
      trichloroacetic acid. Multiple scans of gelsemine metabolites and accurate mass
      measurements were automatically performed simultaneously through data-dependent
      acquisition in only 30 min. The structural elucidations of these metabolites were
      performed by comparing their changes in accurate molecular masses and product
      ions with those of the parent drug. RESULTS: Five metabolites of gelsemine were
      identified in rat liver S9. Of these, four metabolites of gelsemine were
      identified for the first time. The present results showed that the metabolic
      pathways of gelsemine are oxidation, demethylation, and dehydrogenation in rat
      liver S9. CONCLUSIONS: In this study, metabolites of gelsemine in liver S9 were
      identified and elucidated firstly using the HPLC/QqTOF-MS method. The proposed
      metabolic pathways of gelsemine in liver S9 will provide a basis for further
      studies of the in vivo metabolism of gelsemine in animals and humans.

PMID- 29027301
TI  - Challenges of post-authorization safety studies: Lessons learned and results of a
      French study of fentanyl buccal tablet.
AB  - PURPOSE: Recruiting and retaining participants in real-world studies that collect
      primary data are challenging. This article illustrates these challenges using a
      post-authorization safety study (PASS) to assess adverse events (AEs) experienced
      with fentanyl buccal tablet (FBT) over 3 months of treatment. METHODS: This was
      an observational, prospective, multicenter study in France conducted over 1 year.
      The study employed primary data collection in FBT-treated patients and their
      treating physicians via a site qualification questionnaire and patient log
      completed by physicians and a questionnaire and pain diary completed by patients.
      Strategies to increase participation included reminders, newsletters, frequent
      follow-up telephone calls, and reducing the extent of data collected. RESULTS: Of
      the 1118 physicians contacted who returned the participation form or responded to
      a telephone call, only 128 expressed willingness to participate. Key reasons for
      non-participation were lack of interest (69.7%) and FBT not being used in
      practice by the contacted physician (25.1%). Overall, 224 patients were screened
      by 31 physicians, and 97 were enrolled. Key reasons for patient non-inclusion
      were unwillingness or inability to complete the patient AE diary or questionnaire
      (40.9% [52/127]) and patients' decision (33.9% [43/127]). CONCLUSIONS: Despite
      efforts to increase participation, enrollment in this study was low. Recruitment
      and retention methods are limited in their capacity to optimally execute a
      primary data collection in a PASS. For a PASS to provide reliable and valid
      information on medication use, involvement from health care agencies, regulators,
      and pharmaceutical companies is needed to establish their importance, drive study
      participation, and reduce patient withdrawal.

PMID- 29027302
TI  - The re-emerging importance of radiologic-pathologic correlation in reaching the
      pathology diagnosis.

PMID- 29027300
TI  - Pattern of in-hospital changes in drug use in the older people from 2010 to 2016.
AB  - PURPOSE: To assess the pattern of in-hospital changes in drug use in older
      patients from 2010 to 2016. METHODS: People aged 65 years or more acutely
      hospitalized in those internal medicine and geriatric wards that did continuously
      participate to the REgistro POliterapie Societa Italiana di Medicina Interna
      register from 2010 to 2016 were selected. Drugs use were categorized as 0 to 1
      drug (very low drug use), 2 to 4 drugs (low drug use), 5 to 9 drugs
      (polypharmacy), and 10 or more drugs (excessive polypharmacy). To assess whether
      or not prevalence of patients in relation to drug use distribution changed
      overtime, adjusted prevalence ratios (PRs) was estimated with log-binomial
      regression models. RESULTS: Among 2120 patients recruited in 27 wards
      continuously participating to data collection, 1882 were discharged alive and
      included in this analysis. The proportion of patients with very low drug use (0-1
      drug) at hospital discharge increased overtime, from 2.7% in 2010 to 9.2% in
      2016. Results from a log-logistic adjusted model confirmed the increasing PR of
      these very low drug users overtime (particularly in 2014 vs 2012, PR 1.83 95% CI
      1.14-2.95). Moreover, from 2010 to 2016, there was an increasing number of
      patients who, on polypharmacy at hospital admission, abandoned it at hospital
      discharge, switching to the very low drug use group. CONCLUSION: This study shows
      that in internal medicine and geriatric wards continuously participating to the
      REgistro POliterapie Societa Italiana di Medicina Interna register, the
      proportion of patients with a very low drug use at hospital discharge increased
      overtime, thus reducing the therapeutic burden in this at risk population.

PMID- 29027303
TI  - Increased maternal insulin resistance promotes placental growth and decreases
      placental efficiency in pregnancies with obesity and gestational diabetes
      mellitus.
AB  - AIM: Homeostasis model assessment for insulin resistance (HOMA-IR) was measured
      during pregnancy to analyze placental weight and efficiency in relation to
      maternal insulin resistance. METHODS: A retrospective study of 510 pregnant women
      (130 with gestational diabetes mellitus [GDM], 380 with normal glucose tolerance)
      was conducted. We reviewed the patients' demographic data (age, parity, pre
      pregnancy body mass index [BMI]) and perinatal outcomes (birth weight, placental
      weight, BMI at delivery, maternal weight gain, HOMA-IR). The birth weight to
      placental weight (B/P) ratio was calculated for placental efficiency. The
      subjects were categorized by BMI at delivery, and maternal, neonatal and
      placental characteristics were compared between the groups to investigate the
      determinants of placental weight and B/P ratios. RESULTS: Obesity was
      significantly associated with heavier placental weight and lower B/P ratios. The
      presence of GDM did not affect placental weight, whereas the B/P ratios in women
      with GDM were significantly lower than in women with normal glucose tolerance.
      HOMA-IR was positively correlated with placental weight (rho = 0.217, P < 0.001)
      and negatively with B/P ratio (rho = -0.181, P < 0.001). CONCLUSIONS: Increased
      maternal insulin resistance promoted placental growth and inhibited placental
      efficiency. Maternal insulin resistance may be one of the pathophysiological
      conditions responsible for altered placental size and function in pregnancies
      with obesity and GDM.

PMID- 29027305
TI  - Modeling count data in the addiction field: Some simple recommendations.
AB  - Analyzing count data is frequent in addiction studies but may be cumbersome, time
      consuming, and cause misleading inference if models are not correctly specified.
      We compared different statistical models in a simulation study to provide simple,
      yet valid, recommendations when analyzing count data.We used 2 simulation studies
      to test the performance of 7 statistical models (classical or quasi-Poisson
      regression, classical or zero-inflated negative binomial regression, classical or
      heteroskedasticity-consistent linear regression, and Mann-Whitney test) for
      predicting the differences between population means for 9 different population
      distributions (Poisson, negative binomial, zero- and one-inflated Poisson and
      negative binomial, uniform, left-skewed, and bimodal). We considered a large
      number of scenarios likely to occur in addiction research: presence of outliers,
      unbalanced design, and the presence of confounding factors. In unadjusted models,
      the Mann-Whitney test was the best model, followed closely by the
      heteroskedasticity-consistent linear regression and quasi-Poisson regression.
      Poisson regression was by far the worst model. In adjusted models, quasi-Poisson
      regression was the best model. If the goal is to compare 2 groups with respect to
      count data, a simple recommendation would be to use quasi-Poisson regression,
      which was the most generally valid model in our extensive simulations.

PMID- 29027299
TI  - Functional characterization of novel NR5A1 variants reveals multiple complex
      roles in disorders of sex development.
AB  - Variants in the NR5A1 gene encoding SF1 have been described in a diverse spectrum
      of disorders of sex development (DSD). Recently, we reported the use of a
      targeted gene panel for DSD where we identified 15 individuals with a variant in
      NR5A1, nine of which are novel. Here, we examine the functional effect of these
      changes in relation to the patient phenotype. All novel variants tested had
      reduced trans-activational activity, while several had altered protein level,
      localization, or conformation. In addition, we found evidence of new roles for
      SF1 protein domains including a region within the ligand binding domain that
      appears to contribute to SF1 regulation of Mullerian development. There was
      little correlation between the severity of the phenotype and the nature of the
      NR5A1 variant. We report two familial cases of NR5A1 deficiency with evidence of
      variable expressivity; we also report on individuals with oligogenic inheritance.
      Finally, we found that the nature of the NR5A1 variant does not inform patient
      outcomes (including pubertal androgenization and malignancy risk). This study
      adds nine novel pathogenic NR5A1 variants to the pool of diagnostic variants. It
      highlights a greater need for understanding the complexity of SF1 function and
      the additional factors that contribute.

PMID- 29027304
TI  - Sexual Behavior and Heavy Episodic Drinking Across the Transition to Adulthood:
      Differences by College Attendance.
AB  - Despite a growing literature on college students' sexual behaviors, little is
      known about how sexual behaviors, and their associations with alcohol, differ for
      college and noncollege attenders, and whether these patterns represent changes
      during college or an extension of pre-college behaviors. This paper applied time
      varying effect models to data from the National Longitudinal Study of Adolescent
      to Adult Health to examine (1) prevalence of four sexual behaviors from ages 14
      to 24 and (2) how their association with frequent heavy episodic drinking varied
      across these ages for college and noncollege attenders. Nonattenders have higher
      prevalence of all sexual behaviors than college attenders across most ages;
      however, the association between heavy episodic drinking and sexual behaviors is
      stronger for college attenders during ages 18-20.

PMID- 29027306
TI  - Fenton reaction-induced renal carcinogenesis in Mutyh-deficient mice exhibits
      less chromosomal aberrations than the rat model.
AB  - Oxidative stress including iron excess has been associated with carcinogenesis.
      The level of 8-oxoguanine, a major oxidatively modified base in DNA, is
      maintained very low by three distinct enzymes, encoded by OGG1, MUTYH and MTH1.
      Germline biallelic inactivation of MUTYH represents a familial cancer syndrome
      called MUTYH-associated polyposis. Here, we used Mutyh-deficient mice to evaluate
      renal carcinogenesis induced by ferric nitrilotriacetate (Fe-NTA). Although the
      C57BL/6 background is cancer-resistant, a repeated intraperitoneal administration
      of Fe-NTA induced a high incidence of renal cell carcinoma (RCC; 26.7%) in Mutyh
      deficient mice in comparison to wild-type mice (7.1%). Fe-NTA treatment also
      induced renal malignant lymphoma, which did not occur without the Fe-NTA
      treatment in both the genotypes. Renal tumor-free survival after Fe-NTA treatment
      was marginally different (P = 0.157) between the two genotypes. Array-based
      comparative genome hybridization analyses revealed, in RCC, the loss of
      heterozygosity in chromosomes 4 and 12 without p16INKA inactivation; these
      results were confirmed by a methylation analysis and showed no significant
      difference between the genotypes. Lymphomas showed a preference for genomic
      amplifications. Dlk1 inactivation by promoter methylation may be involved in
      carcinogenesis in both tumors. Fe-NTA-induced murine RCCs revealed significantly
      less genomic aberrations than those in rats, demonstrating a marked species
      difference.

PMID- 29027307
TI  - Transient amniotic fluid leakage after fetoscopic laser photocoagulation for twin
      twin transfusion syndrome.
AB  - AIM: Iatrogenic premature rupture of membrane (PROM) is one of the major
      complications related to fetoscopic laser photocoagulation (FLP) for twin-twin
      transfusion syndrome (TTTS). However, amniotic fluid leakage (AFL) sometimes
      spontaneously disappears. This study evaluated the incidence and clinical
      characteristics of transient AFL after FLP. METHODS: We retrospectively reviewed
      pregnancies that underwent FLP for TTTS at a single center. Patients with
      apparent AFL within 2 weeks after FLP were divided into two groups: transient
      AFL, defined by the disappearance of fluid leakage within a week; and PROM, if
      AFL persisted continuously for more than a week or premature birth occurred,
      including miscarriage, within a week of the first symptom of AFL. RESULTS: Among
      201 monochorionic twin pregnancies that underwent FLP during the study period,
      nine patients (4.5%) were diagnosed with AFL within a week after FLP. Four
      patients (2.0%) were classified as transient AFL and five as PROM. Median
      gestational age at FLP was not significantly different between the groups;
      operative time in the PROM group was significantly longer (P = 0.01). The surgery
      to delivery interval and median gestational age at delivery were greater in the
      transient AFL group (87.8 vs 17.6 days, P = 0.01; 32.5 vs 23.6 weeks, P = 0.01,
      respectively). CONCLUSIONS: The incidence of transient AFL after FLP was 2%.
      Perinatal outcomes of transient AFL might be better than that of PROM.

PMID- 29027308
TI  - Animal models for analyzing metabolic syndrome-associated liver diseases.
AB  - Metabolic syndrome (MS) is a worldwide healthcare issue and a dominant risk
      factor for the development of incurable diseases affecting the entire body. The
      hepatic manifestations of MS include nonalcoholic fatty liver disease (NAFLD) and
      its progressive variant, nonalcoholic steatohepatitis (NASH). NASH is known to
      progress to liver cirrhosis and hepatocellular carcinoma (HCC). Excellent animal
      models for determining the mechanism of pathogenesis and establishing therapeutic
      treatment of NASH/HCC are strongly required worldwide. We recently reported that
      two previously established mouse models of obesity and diabetes mellitus, namely,
      Tsumura-Suzuki Obese Diabetes (TSOD) mice and MSG mice, developed MS-associated
      NASH and that their clinical course and pathological characteristics closely
      mimicked those of human MS-NASH patients. Interestingly, most of the mice
      developed HCC with advancing age, and the pathological and functional
      characteristics of this condition were identical to those of human HCC. We
      further established a novel mouse model of HCC based on type 1 diabetes (DIAR
      nSTZ mice) and reported its histopathological features. By comparing various
      aspects of these mouse models, specific and useful characteristics in a suitable
      model of MS-associated liver diseases, including hepato-carcinogenesis, can be
      highlighted.

PMID- 29027310
TI  - Ruptured external iliac artery pseudoaneurysm following surgery for ovarian
      cancer: A case report and literature review.
AB  - Ruptured pseudoaneurysm following pelvic surgery is a rare and fatal
      complication. Because of its rarity, existing evidence is limited to a small case
      series. A 60-year-old woman underwent staging laparotomy, including pelvic and
      para-aortic lymphadenectomy, for ovarian cancer. On the 11th day, the patient
      developed a sudden lumbar pain and loss of consciousness, which resulted in a
      state of shock. She was diagnosed as having a pelvic abscess and ruptured
      external iliac artery pseudoaneurysm. We performed ligation of the external iliac
      artery to restrain hemorrhage and femoro-femoral artery bypass to prevent
      infection, which saved the patient's life. Our study had two findings. First,
      this is the first reported case of ruptured external iliac artery pseudoaneurysm
      following surgery for ovarian cancer. Second, treatment of ruptured
      pseudoaneurysm requires rapid hemostasis, prevention of infection, and
      revascularization.

PMID- 29027309
TI  - The importance of symptoms in the longitudinal variability of clusters in COPD
      patients: A validation study.
AB  - BACKGROUND AND OBJECTIVE: Cluster analysis has been utilized to explore
      phenotypic heterogeneity in chronic obstructive pulmonary disease (COPD). To
      date, little is known about the longitudinal variability of clusters in COPD
      patients. We aimed to evaluate the 2-year cluster variability in stable COPD
      patients. METHODS: We evaluated the following variables in COPD patients at
      baseline and 2 years later: age, gender, pack-year history, body mass index
      (BMI), modified Medical Research Council (MMRC) scale, 6-min walking distance
      (6MWD), spirometry and COPD Assessment Test (CAT). Patient classification was
      performed using cluster analysis at baseline and 2 years later. Each patient's
      cluster variability after 2 years and its parameters associated with cluster
      change were explored. RESULTS: A total of 521 smokers with COPD were evaluated at
      baseline and 2 years later. Three different clusters were consistently identified
      at both evaluation times: cluster A (of younger age, mild airway limitation, few
      symptoms), cluster B (intermediate) and cluster C (of older age, severe airway
      limitation and highly symptomatic). Two years later, 70% of patients were
      unchanged, whereas 30% changed from one cluster to another: 20% from A to B; 15%
      from B to A; 15% from B to C; 42% from C to B and 8% from C to A. 6MWD, forced
      expiratory volume in 1 s (FEV1 ) % and CAT were the principal parameters
      responsible for this change. CONCLUSION: After 2 years of follow-up, most of the
      COPD patients maintained their cluster assignment. Exercise tolerance, lung
      function and quality of life were the main driving parameters in those who change
      their cluster assignment.

PMID- 29027311
TI  - Natural Compound Licochalcone B Induced Extrinsic and Intrinsic Apoptosis in
      Human Skin Melanoma (A375) and Squamous Cell Carcinoma (A431) Cells.
AB  - Licochalcone B (Lico B), which is normally isolated from the roots of Glycyrrhiza
      inflata (Chinese Licorice), generally classified into organic compounds including
      retrochalcones. Potential pharmacological properties of Lico B include anti
      inflammatory, anti-bacterial, anti-oxidant, and anti-cancer activities. However,
      its biological effects on melanoma and squamous cell carcinoma (SCC) are unknown.
      Based on these known facts, this study investigated the role of Lico B in
      apoptosis, through the extrinsic and intrinsic pathways and additional regulation
      of specificity protein 1 in human skin cancer cell lines. Annexin V/7
      aminoactinomycin D staining, western blot analysis, mitochondrial membrane
      potential assay, and an anchorage-independent cell transformation assay
      demonstrated that Lico B treatment of human melanoma and SCC cells significantly
      inhibited cell proliferation and induced apoptotic cell death. More specifically,
      Lico B induced apoptosis through the regulation of specificity protein 1 and
      apoptosis-related proteins including CCAAT/enhancer-binding protein homologous
      protein, death receptors, and poly (ADP-ribose) polymerase. These results
      indicate that Lico B has apoptotic effect on A375 and A431 skin cancer cells,
      suggesting the potential value of Lico B for the treatment of human melanoma and
      SCC. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 29027312
TI  - Cyclophilin A expression and its prognostic significance in lung adenocarcinoma.
AB  - Cyclophilin A (CypA) has been reported to be upregulated in malignant tumors.
      CypA expression is thought to be associated with acquisition of tumor growth and
      anti-apoptotic function. Although upregulation of CypA has been reported in lung
      adenocarcinoma, its clinicopathological significance and roles in malignant
      progression remain unclear. Here we investigated the implications of CypA
      expression for outcome in patients with lung adenocarcinoma. Lung adenocarcinoma
      specimens from 198 cases were selected and reclassified according to the World
      Health Organization classification (4th edition) and the Noguchi classification.
      CypA expression was assessed by immunohistochemistry, and the H-score was
      calculated on the basis of intensity and proportion. The specificity of the
      antibody used was confirmed by Western blotting and the cut-off point was
      determined from the ROC curve. Sixty-seven cases (33.8%) had low CypA expression
      (CypA-L group) and 131 (66.2%) had high CypA expression (CypA-H group). Many
      cases of adenocarcinoma in situ were CypA-L, and advanced adenocarcinomas tended
      to be classified as CypA-H. Clinically, patients with CypA-H tumors showed a
      significantly poorer prognosis than those with CypA-L tumors. This is the first
      investigation of the implications of the CypA expression level in terms of the
      clinical characteristics of resected lung adenocarcinomas.

PMID- 29027313
TI  - Patient experiences with care across various types of mental health care:
      Questionnaire development, measurement invariance, and patients' reports.
AB  - To describe the development, validation, and findings of a patient experience
      questionnaire across 7 types of residential and ambulatory mental health care
      services. Thirty-five items were hypothesized to cover information,
      participation, therapeutic relationship, personalized care, organization and
      collaboration, safety, patient rights, outcomes of care, and discharge
      preparation and after-care. Also included were 2 overall rating items (scoring
      and recommending the organization). This Dutch questionnaire was applied in 79
      organizations in Belgium (N patients = 5,168). Exploratory structural equation
      modelling was conducted on a random split-half sample to examine dimensionality.
      Confirmatory factor analysis and multiple group confirmatory factor analyses were
      conducted on the holdout sample to confirm dimensionality and assess measurement
      invariance across type of service and patient characteristics. Multilevel
      logistic regression models linking subscale top box scores to overall rating
      items were used to assess criterion validity. The hypothesized dimensionality was
      partly confirmed, and configural and scalar invariance were demonstrated across
      types of organizations and patient characteristics. Subscale scores were
      significantly associated with overall ratings. Process evaluation showed that
      participating organizations strongly support continued use of this questionnaire.
      This validated patient experience questionnaire supports comparison across
      organizations from different types of services to improve the quality of mental
      health care.

PMID- 29027316
TI  - Abstracts of the 10th European Congress on Tropical Medicine and International
      Health, 16-20 October 2017, Antwerp, Belgium.

PMID- 29027314
TI  - The relationship between attitudes toward aging and health-promoting behaviours
      in older adults.
AB  - BACKGROUND: Identifying the factors that are associated with health-promoting
      behaviours in older adults is necessary to increase their willingness and
      motivation to participate in health-promotion activities. Understanding context
      specific attitudes in relation to their influence on health-promoting behaviours
      is crucial in designing efficient interventions that foster health-promoting
      behaviours among older adults. AIM: This study aimed to examine the relationships
      between attitudes towards aging and health-promoting behaviours in older adults
      in Turkey. METHODS: The study used a descriptive-correlational design. A
      convenience sample of 448 community-dwelling older adults who were 65 years and
      older and cognitively intact were selected from 6 family health centres in the
      city of Denizli in Turkey. The data were collected between March and June of 2014
      using the Attitudes to Aging Questionnaire and the Health-Promoting Lifestyle
      Profile II. Multiple linear regression analysis was performed to explore the
      predictors of health-promoting behaviours. FINDINGS: Attitudes toward aging, the
      psychosocial loss subscale, and education were statistically significant
      predictors of health-promoting behaviours. Attitudes toward aging were the
      strongest predictor of health-promoting behaviours in older adults. CONCLUSION:
      Attitude towards aging is a factor that affects health-promoting behaviours, and
      it should be considered during interventions for improving health promoting
      behaviours.

PMID- 29027315
TI  - Cost effectiveness analysis of carbetocin during cesarean section in a high
      volume maternity unit.
AB  - AIM: To evaluate the cost effectiveness of carbetocin compared to oxytocin when
      used as prophylaxis against post-partum hemorrhage (PPH) during cesarean
      deliveries. METHODS: A systematic review of the literature was performed to
      identify randomized controlled trials that compared the use of carbetocin to
      oxytocin in the context of cesarean deliveries. Cost effectiveness analysis was
      then performed using secondary data from the perspective of a maternity unit
      within the Malaysian Ministry of Health, over a 24 h time period. RESULTS: Seven
      randomized controlled trials with over 2000 patients comparing carbetocin with
      oxytocin during cesarean section were identified. The use of carbetocin in our
      center, which has an average of 3000 cesarean deliveries annually, would have
      prevented 108 episodes of PPH, 104 episodes of transfusion and reduced the need
      for additional uterotonics in 455 patients. The incremental cost effectiveness
      ratio of carbetocin for averting an episode of PPH was US$278.70. CONCLUSION:
      Reduction in retreatment, staffing requirements, transfusion and potential
      medication errors mitigates the higher index cost of carbetocin. From a
      pharmacoeconomic perspective, in the context of cesarean section, carbetocin was
      cost effective as prophylaxis against PPH. Ultimately, the relative value placed
      on the outcomes above and the individual unit's resources would influence the
      choice of uterotonic.

PMID- 29027318
TI  - Imaging and pathology features to predict axillary tumor load in breast cancer.
AB  - AIM: We investigated if imaging and pathology features could help to identify a
      high axillary tumor burden (ATB) in breast cancer patients, in order to
      individualize decisions on axillary lymph node (ALN) dissection (ALND). METHODS:
      We retrospectively analyzed patients primarily treated with surgery in our unit
      between 2011 and 2014. We divided the patients in two groups: low ATB (LATB) if
      <= 2 ALN were infiltrated and high ATB (HATB) if > 2 ALN were infiltrated.
      RESULTS: Data of 105 patients was included in the study. Axillary ultrasound
      (AUS) features associated with HATB were any sign of ALN infiltration (76 vs 24%,
      P = 0.027) and > 2 suspicious ALNs (73% vs 27%, P = 0.018); however, when AUS
      revealed <= 2 suspicious ALNs, 39% of these patients had HATB. Any sign of ALN
      infiltration on magnetic resonance imaging was associated with HATB (48% vs 52%,
      P = 0.031). Positive preoperative ALN cytology or biopsy was associated with HATB
      (53% vs 47%, P = 0.008), while p53 positivity (80% vs 20%) and high histological
      grade (68% vs. 32%) correlated with LATB (P = 0.05 and P = 0.02, respectively).
      In multivariate analysis, only positive preoperative ALN cytology or biopsy was
      associated with HATB (P = 0.038). CONCLUSIONS: AUS was useful for detecting HATB
      but was not as effective in patients with LATB. Proving axillary infiltration
      with AUS-directed cytology or biopsy is the most effective method to predict
      HATB.

PMID- 29027319
TI  - Pregnancy in immunoglobulin M nephropathy.
AB  - Immunoglobulin M nephropathy is an uncommon glomerular disease and a relatively
      less recognized clinico-immunopathological entity in the domain of
      glomerulonephritis, often thought to be a bridge between minimal change disease
      and focal segmental glomerulosclerosis. It is characterized by asymptomatic
      hematuria, episodes of macroscopic hematuria and proteinuria. Corticosteroids
      remain the mainstay of therapeutic strategies for such patients. We present what
      we believe to be the first known case of successful pregnancy in a 40-year-old
      woman with a 12-year history of underlying immunoglobulin M nephropathy. In view
      of the rarity of this disease we hope this report will assist professionals
      managing such cases.

PMID- 29027320
TI  - Trends in oncoplastic breast surgery and breast reconstruction over the past 35
      years.

PMID- 29027317
TI  - Exposure to omentum adipose tissue conditioned medium from obese pregnant women
      promotes myometrial artery dysfunction.
AB  - AIM: Underlying mechanisms of poor pregnancy outcome in obese (OB) mothers (body
      mass index [BMI] >= 30 kg/m2 ) are unknown. Our studies demonstrate that OB
      pregnant women have altered myometrial artery (MA) function related to the
      thromboxane and nitric oxide pathways. In obesity, increased central fat mass is
      associated with an altered endocrine milieu. We tested the hypothesis that in OB
      pregnant women the omentum, a central fat store, releases factors that promote
      dysfunction in normal MAs. METHODS: Myometrial and omental adipose tissue
      biopsies were obtained from women with uncomplicated term pregnancies. Omental
      adipose tissue explants from six normal weight (NW; BMI 18.5-24.9 kg/m2 ) and six
      OB (BMI >= 30 kg/m2 ) women were cultured and the conditioned medium collected
      and pooled to produce NW medium and OB medium. Adipokine concentrations were
      measured using enzyme-linked immunosorbent assays. Wire myography was used to
      assess the effect of conditioned medium (NW or OB; N = 7) or leptin (100 nM; N =
      5) exposure on MA responses to U46619 (thromboxane-mimetic) and bradykinin
      (endothelial-dependent vasodilator). RESULTS: OB medium had higher leptin and
      lower adiponectin levels than NW medium. U46619 and bradykinin concentration
      response curves shifted upwards in MAs exposed to OB medium but were unaffected
      by leptin. CONCLUSIONS: Omental adipose tissue from OB pregnant women produced
      altered concentrations of adipokines. Acute OB medium exposure induced MA
      dysfunction, an effect not mirrored by exposure to leptin. These data suggest
      that an aberrant endocrine environment created by increased central adiposity in
      OB pregnant women induces vascular endothelial dysregulation, which may
      predispose them to a poor pregnancy outcome.

PMID- 29027321
TI  - Jumping down the rabbit hole: unravelling the right ventricle in heart failure.

PMID- 29027322
TI  - Inotropes and vasopressors in acute heart failure, when the devil dresses as an
      angel.

PMID- 29027323
TI  - Response to 'Silent uterine rupture occluded by intestinal adhesions following
      laparoscopic myomectomy: A case report': Do some remain permanently silent?

PMID- 29027324
TI  - Circulating microRNA-132 levels improve risk prediction for heart failure
      hospitalization in patients with chronic heart failure.
AB  - AIMS: Non-coding microRNAs (miRNAs) are critically involved in cardiovascular
      pathophysiology. Since they are measurable in most body fluids, they have been
      proposed as circulating biomarkers. We examined the prognostic value of a
      specific candidate miRNA in a large cohort of patients with chronic heart failure
      (HF) enrolled in a multicentre clinical trial. METHODS AND RESULTS: Plasma levels
      of miR-132 were measured using miRNA-specific PCR-based technologies at
      randomization in 953 patients with chronic, symptomatic HF from the GISSI-Heart
      Failure trial. The association with fatal (all-cause and cardiovascular death)
      and non-fatal events (time to first admission to hospital for cardiovascular
      reasons or worsening of HF) and the incremental risk prediction were estimated in
      adjusted models. Higher circulating miR-132 levels were independently associated
      with younger age, better renal filtration, ischaemic aetiology of HF, more severe
      HF symptoms, higher diastolic blood pressure, higher cholesterol, and male sex.
      After extensive adjustment for demographic, clinical, and echocardiographic risk
      factors and baseline NT-proBNP concentrations, miR-132 remained associated only
      with HF hospitalizations (hazard ratio 0.79, 95% confidence interval 0.66-0.95, P
      = 0.01) and improved its risk prediction with the continuous net reclassification
      index (cNRI 0.205, P = 0.001). CONCLUSION: In well characterized patients with
      chronic HF, circulating miR-132 levels rise with the severity of HF. Lower
      circulating miR-132 levels improved risk prediction for HF readmission beyond
      traditional risk factors, but not for mortality. MiR-132 may be helpful to
      intensify strategies aimed at reducing re-hospitalization, which has a
      substantial health and economic burden in HF.

PMID- 29027326
TI  - Daytime periodic breathing during short-term laboratory recordings in heart
      failure patients: the iceberg tip of central sleep apnoea?

PMID- 29027327
TI  - Laparoscopic ventral hernia repair using only 5-mm ports.
AB  - BACKGROUND: The technique of laparoscopic ventral hernia repair has been evolving
      since it was first described over 20 years ago. We report a new technique where
      polyester mesh was back loaded through a 5-mm port site, coming into contact with
      the skin. This avoids the need for any 10-12-mm ports. METHODS: A prospective
      database of laparoscopic ventral hernia repairs was examined. A single surgeon
      performed 344 laparoscopic ventral hernia repairs using this technique over 60
      months. Follow-up was conducted by both clinical and independent phone review.
      SURGICAL TECHNIQUE: Laparoscopic access was achieved via a 5-mm optical port,
      adding two, or occasionally three, 5-mm extra ports. Hernia contents were reduced
      and the extra-peritoneal fat excised; 5-mm tooth graspers were placed through the
      lateral port and then in a retrograde fashion through the uppermost port. The
      port was removed, and the mesh pulled back into the abdominal cavity and
      positioned with a minimum of 3-cm overlap. The mesh was fixed using absorbable
      tacks and sutures. RESULTS: Most patients had primary umbilical hernias. There
      was one case of mesh infection due to enteric organisms. This occurred in a
      patient undergoing repair of a stoma site hernia, resulting from a Hartmann's
      procedure for perforated diverticulitis. There was no other evidence of acute or
      chronic mesh infection despite cutaneous contact with the mesh. In this series,
      there was an overall hernia recurrence rate of 2.4%. CONCLUSION: Laparoscopic
      ventral hernia repair using only 5-mm ports is a safe, effective technique with
      no extra risk of infection.

PMID- 29027325
TI  - Ecological plant epigenetics: Evidence from model and non-model species, and the
      way forward.
AB  - Growing evidence shows that epigenetic mechanisms contribute to complex traits,
      with implications across many fields of biology. In plant ecology, recent studies
      have attempted to merge ecological experiments with epigenetic analyses to
      elucidate the contribution of epigenetics to plant phenotypes, stress responses,
      adaptation to habitat, and range distributions. While there has been some
      progress in revealing the role of epigenetics in ecological processes, studies
      with non-model species have so far been limited to describing broad patterns
      based on anonymous markers of DNA methylation. In contrast, studies with model
      species have benefited from powerful genomic resources, which contribute to a
      more mechanistic understanding but have limited ecological realism. Understanding
      the significance of epigenetics for plant ecology requires increased transfer of
      knowledge and methods from model species research to genomes of evolutionarily
      divergent species, and examination of responses to complex natural environments
      at a more mechanistic level. This requires transforming genomics tools
      specifically for studying non-model species, which is challenging given the large
      and often polyploid genomes of plants. Collaboration among molecular geneticists,
      ecologists and bioinformaticians promises to enhance our understanding of the
      mutual links between genome function and ecological processes.

PMID- 29027328
TI  - Rare case of Bouveret syndrome.

PMID- 29027329
TI  - Duration of chronic heart failure affects outcomes with preserved effects of
      heart rate reduction with ivabradine: findings from SHIFT.
AB  - AIMS: In heart failure (HF) with reduced ejection fraction and sinus rhythm,
      heart rate reduction with ivabradine reduces the composite incidence of
      cardiovascular death and HF hospitalization. METHODS AND RESULTS: It is unclear
      whether the duration of HF prior to therapy independently affects outcomes and
      whether it modifies the effect of heart rate reduction. In SHIFT, 6505 patients
      with chronic HF (left ventricular ejection fraction of <=35%), in sinus rhythm,
      heart rate of >=70 b.p.m., treated with guideline-recommended therapies, were
      randomized to placebo or ivabradine. Outcomes and the treatment effect of
      ivabradine in patients with different durations of HF were examined. Prior to
      randomization, 1416 ivabradine and 1459 placebo patients had HF duration of >=4
      weeks and <1.5 years; 836 ivabradine and 806 placebo patients had HF duration of
      1.5 years to <4 years, and 989 ivabradine and 999 placebo patients had HF
      duration of >=4 years. Patients with longer duration of HF were older (62.5 years
      vs. 59.0 years; P < 0.0001), had more severe disease (New York Heart Association
      classes III/IV in 56% vs. 44.9%; P < 0.0001) and greater incidences of co
      morbidities [myocardial infarction: 62.9% vs. 49.4% (P < 0.0001); renal
      dysfunction: 31.5% vs. 21.5% (P < 0.0001); peripheral artery disease: 7.0% vs.
      4.8% (P < 0.0001)] compared with patients with a more recent diagnosis. After
      adjustments, longer HF duration was independently associated with poorer outcome.
      Effects of ivabradine were independent of HF duration. CONCLUSIONS: Duration of
      HF predicts outcome independently of risk indicators such as higher age, greater
      severity and more co-morbidities. Heart rate reduction with ivabradine improved
      outcomes independently of HF duration. Thus, HF treatments should be initiated
      early and it is important to characterize HF populations according to the
      chronicity of HF in future trials.

PMID- 29027330
TI  - Poor nutrition from first foods: A cross-sectional study of complementary feeding
      of infants and young children in six remote Aboriginal communities across
      northern Australia.
AB  - AIM: To describe the first foods of Aboriginal and Torres Strait Islander infants
      and young children who were recruited to a nutrition promotion and anaemia
      prevention program conducted from 2010 to 2012, in six remote communities across
      northern Australia. METHODS: Food records (24-hour diet history, food variety
      checklist) were completed on recruitment by interview with a parent or carer.
      Cross-sectional analysis assessed the proportion of participants consuming
      recommended and not-recommended foods and drinks and meeting recommendations for
      meal frequency and dietary diversity. RESULTS: Of 245 Aboriginal and Torres
      Strait Islander participants aged 6-24 months, 227 (92.7%) had a recruitment food
      record. On the previous day, most (67.4%) had breastmilk, nearly all (98.2%) ate
      solid food, but only 13% ate fruit, 33% had neither fruit nor vegetables, and 25%
      had sweet drinks. Children living in smaller households (3-5 people) were more
      likely to meet the criteria for frequency of meals than those living in larger
      households of 12-31 people (93% vs 78%, P = 0.012 for trend over household size).
      Only 30% met the criteria for dietary diversity. Where information was available
      (n = 91), dietary diversity was adequate more often in 'pay week' compared to
      'not pay week' (31.3% vs 9.3%, P = 0.007). CONCLUSION: Support for current
      beneficial breast-feeding practices and promotion of nutrient-dense complementary
      foods, need to be embedded in initiatives for improved family food security. Good
      nutrition in early life can reduce the disparity in health, education and
      economic status between Aboriginal and Torres Strait Islander peoples and other
      Australians.

PMID- 29027331
TI  - When does it pay to invest in a patch? The evolution of intentional niche
      construction.
AB  - Humans modify their environments in ways that significantly transform the earth's
      ecosystems. Recent research suggests that such niche-constructing behaviors are
      not passive human responses to environmental variation, but instead should be
      seen as active and intentional management of the environment. Although such
      research is useful in highlighting the interactive dynamics between humans and
      their natural world, the niche-construction framework, as currently applied,
      fails to explain why people would decide to modify their environments in the
      first place. To help resolve this problem, we use a model of technological
      intensification to analyze the cost-benefit trade-offs associated with niche
      construction as a form of patch investment. We use this model to assess the costs
      and benefits of three paradigmatic cases of intentional niche construction in
      Western North America: the application of fire in acorn groves, the manufacture
      of fishing weirs, and the adoption of maize agriculture. Intensification models
      predict that investing in patch modification (niche construction) only provides a
      net benefit when the amount of resources needed crosses a critical threshold that
      makes the initial investment worthwhile. From this, it follows that low-cost
      investments, such as burning in oak groves, should be quite common, while more
      costly investments, such as maize agriculture, should be less common and depend
      on the alternatives available in the local environment. We examine how patterns
      of mobility, risk management, territoriality, and private property also co-evolve
      with the costs and benefits of niche construction. This approach illustrates that
      explaining niche-constructing behavior requires understanding the economic trade
      offs involved in patch investment. Integrating concepts from niche construction
      and technological intensification models within a behavioral ecological framework
      provides insights into the coevolution and active feedback between adaptive
      behaviors and environmental change across human history.

PMID- 29027332
TI  - Demic and cultural diffusion in prehistoric Europe in the age of ancient genomes.
AB  - Ancient genomes can help us detect prehistoric migrations, population
      contractions, and admixture among populations. Knowing the dynamics of demography
      is invaluable for understanding culture change in prehistory, particularly the
      roles played by demic and cultural diffusion in transformations of material
      cultures. Prehistoric Europe is a region where ancient genome analyses can help
      illuminate the interplay between demography and culture change. In Europe, there
      is more archeological evidence, in terms of detailed studies, radiometric dates,
      and explanatory hypotheses that can be evaluated, than in any other region of the
      world. Here I show some important ways that ancient genomes have given us
      insights into population movements in European prehistory. I also propose that
      studies might be increasingly focused on specific questions of culture change,
      for example in evaluating the makers of "transitional" industries as well as the
      origins of the Gravettian and spread of the Magdalenian. I also discuss genomic
      evidence supporting the large role that demic expansion has played in the
      Neolithization of Europe and the formation of the European population during the
      Bronze Age.

PMID- 29027333
TI  - From your seat on the train: Even in science, what you see depends on your point
      of view.

PMID- 29027334
TI  - Anthropologists get jazzed for science in New Orleans.

PMID- 29027335
TI  - Occasional, obligatory, and habitual stone tool use in hominin evolution.
AB  - Archeologists have long assumed that earlier hominins were obligatory stone tool
      users. This assumption is deeply embedded in traditional ways of describing the
      lithic record. This paper argues that lithic evidence dating before 1.7 Ma
      reflects occasional stone tool use, much like that practiced by nonhuman primates
      except that it involved flaked-stone cutting tools. Evidence younger than 0.3 Ma
      is more congruent with obligatory stone tool use, like that among recent humans.
      The onset of habitual stone tool use at about 1.7 Ma appears correlated with
      increased hominin logistical mobility (carrying things). The onset of obligatory
      stone tool use after 0.3 Ma may be linked to the evolution of spoken language.
      Viewing the lithic evidence dating between 0.3-1.7 Ma as habitual stone tool use
      explains previously inexplicable aspects of the Early-Middle Pleistocene lithic
      record.

PMID- 29027336
TI  - Trends in utilization of benzodiazepine and Z-drugs in Israel.
AB  - BACKGROUND: Studies on benzodiazepine (BZDs) as well as Zopiclone and Zolpidem (Z
      drugs) utilization are important for estimating the prevalence of medical
      conditions, providing the basis for pharmacovigilance, and identifying temporal
      trends of consumption. Such studies that involve the Israeli population have not
      been conducted yet. PURPOSE: Identify trends over time in utilization of BZDs and
      Z-drugs in a nationwide population in Israel. METHODS: Data on BZD and Z-drugs
      utilization (for all indications) for the period 2005 to 2013 were obtained from
      pharmaceutical companies that distribute BZDs in Israel. Prevalence of BZD
      utilization was reported as defined daily doses (DDD)/1000 inhabitants/day.
      RESULTS: The utilization of BZDs and Z-drugs aimed to treat sleeping disorders
      increased over the period of the study from 10.22 to 22.49 DDD/1000
      inhabitants/day. The greatest increases in utilization of drugs established in
      Israel were observed for brotizolam (83%), zopiclone (59%), and zolpidem (94%).
      Decreases in use were recorded for lorazepam (14%), diazepam (16%), and oxazepam
      (27%). Use of hypnotic BZDs appeared to be relatively high, compared with the use
      of non-BZD hypnotics ("Z-drugs") such as zolpidem or zopiclone. Nationwide
      stressful conditions did not appear to be reflected in the annual BZD sales.
      CONCLUSIONS: Conventional BZDs and Z-drugs remained the treatment of choice for
      sleeping disorders in Israel during the study period. These results are, in
      certain cases, in contrast to current practice recommendations and guidelines and
      point at a need in better dissemination of these guidelines among prescribers in
      Israel.

PMID- 29027337
TI  - Acute kidney injury in cardiogenic shock: in search of early detection and
      clinical certainty.

PMID- 29027338
TI  - Stoichiometric distribution models: ecological stoichiometry at the landscape
      extent.
AB  - Human activities are altering the fundamental geography of biogeochemicals. Yet
      we lack an understanding of how the spatial patterns in organismal stoichiometry
      affect biogeochemical processes and the tools to predict the impacts of global
      changes on biogeochemical processes. In this contribution we develop
      stoichiometric distribution models (StDMs), which allow us to map spatial
      structure in resource elemental composition across a landscape and evaluate
      spatial responses of consumers. We parameterise StDMs for a consumer-resource
      (moose-white birch) system and demonstrate that we can develop predictive models
      of resource stoichiometry across a landscape and that such models could improve
      our predictions of consumer space use. With results from our study system
      application, we argue that explicit consideration of the spatial patterns in
      organismal elemental composition may uncover emergent individual, population,
      community and ecosystem properties that are not revealed at the local extents
      routinely used in ecological stoichiometry. We discuss perspectives for further
      developments and application of StDMs to advance three emerging frameworks for
      spatial ecosystem ecology in an era of global change; meta-ecosystem theory,
      macroecological stoichiometry and remotely sensed biogeochemistry. Progress on
      these emerging frameworks will allow for the integration of ecological
      stoichiometry and individual space use and fitness.

PMID- 29027339
TI  - Evidence of continuity of mesentery from duodenum to rectum from human cadaveric
      dissection - a video vignette.

PMID- 29027340
TI  - Can I get pregnant again?

PMID- 29027341
TI  - Tropical soils are a reservoir for fluorescent Pseudomonas spp. biodiversity.
AB  - Fluorescent Pseudomonas spp. are widely studied for their beneficial activities
      to plants. To explore the genetic diversity of Pseudomonas spp. in tropical
      regions, we collected 76 isolates from a Brazilian soil. Genomes were sequenced
      and compared to known strains, mostly collected from temperate regions.
      Phylogenetic analyses classified the isolates in the P. fluorescens (57) and P.
      putida (19) groups. Among the isolates in the P. fluorescens group, most (37)
      were classified in the P. koreensis subgroup and two in the P. jessenii subgroup.
      The remaining 18 isolates fell into two phylogenetic subclades distinct from
      currently recognized P. fluorescens subgroups, and probably represent new
      subgroups. Consistent with their phylogenetic distance from described subgroups,
      the genome sequences of strains in these subclades are asyntenous to the genome
      sequences of members of their neighbour subgroups. The tropical isolates have
      several functional genes also present in known fluorescent Pseudomonas spp.
      strains. However, members of the new subclades share exclusive genes not detected
      in other subgroups, pointing to the potential for novel functions. Additionally,
      we identified 12 potential new species among the 76 isolates from the tropical
      soil. The unexplored diversity found in the tropical soil is possibly related to
      biogeographical patterns.

PMID- 29027342
TI  - Study on nutritional monitoring of Persian malnourished school students: A check
      on reproducibility and validity of questionnaire.
AB  - AIM: To develop a nutritional screening tool and examine its reliability and
      validity in elementary school children with malnutrition based on PRECEDE-PROCEED
      model, in Shiraz, Iran. METHODS: A questionnaire was designed and its
      reproducibility was analysed via test-retest design among students with
      malnutrition. The students were in the fourth to sixth grades. Validity was
      assessed using face validity, content validity, construct validity, item
      difficulty and item discrimination. Reliability was measured by Cronbach's alpha
      (internal consistency), the intra-class correlation coefficient (ICC) and kappa
      statistics (test-retest reliability). RESULTS: A total of 165 primary school
      students (mean age of 11.21 +/- 1.08 years, 65.5% females) participated in the
      study. The PRECEDE-PROCEED theoretical model for health education was adapted for
      this questionnaire. The questionnaire was divided into four main sections:
      predisposing, reinforcing, enabling factors and behaviour. Coefficient alpha
      reliability estimate was above 0.9 for most scales. The ICCs for different scales
      of the questionnaire were within the range of 0.402-0.800. Values for kappa
      ranged from 0.412 to 0.785 for most scales. CONCLUSIONS: The results showed
      reasonable validity, excellent reliability and moderate to substantial
      reproducibility for all scales of the questionnaire except two questions for
      kappa statistics. The present study is of great importance, as there are no
      psychometrically evaluated tools (based on health behaviour models) with accepted
      validity and reliability for the evaluation of such factors in children with
      malnutrition. The questionnaire developed in the present study can be used to
      assess the effect of intervention among primary school students with
      malnutrition.

PMID- 29027343
TI  - Species reordering, not changes in richness, drives long-term dynamics in
      grassland communities.
AB  - Determining how ecological communities will respond to global environmental
      change remains a challenging research problem. Recent meta-analyses concluded
      that most communities are undergoing compositional change despite no net change
      in local species richness. We explored how species richness and composition of co
      occurring plant, grasshopper, breeding bird and small mammal communities in arid
      and mesic grasslands changed in response to increasing aridity and fire
      frequency. In the arid system, grassland and shrubland plant and breeding bird
      communities were undergoing directional change, whereas grasshopper and small
      mammal communities were stable. In the mesic system, all communities were
      undergoing directional change regardless of fire frequency. Despite directional
      change in composition in some communities, species richness of all communities
      did not change because compositional change resulted more from reordering of
      species abundances than turnover in species composition. Thus, species
      reordering, not changes in richness, explains long-term dynamics in these grass
      and shrub dominated communities.

PMID- 29027344
TI  - Species are not most abundant in the centre of their geographic range or climatic
      niche.
AB  - The pervasive idea that species should be most abundant in the centre of their
      geographic range or centre of their climatic niche is a key assumption in many
      existing ecological hypotheses and has been declared a general macroecological
      rule. However, empirical support for decreasing population abundance with
      increasing distance from geographic range or climatic niche centre (distance
      abundance relationships) remains fairly weak. We examine over 1400 bird, mammal,
      fish and tree species to provide a thorough test of distance-abundance
      relationships, and their associations with species traits and phylogenetic
      relationships. We failed to detect consistent distance-abundance relationships,
      and found no association between distance-abundance slope and species traits or
      phylogenetic relatedness. Together, our analyses suggest that distance-abundance
      relationships may be rare, difficult to detect, or are an oversimplification of
      the complex biogeographical forces that determine species spatial abundance
      patterns.

PMID- 29027345
TI  - A Strategy for Specific Fluorescence Imaging of Monoamine Oxidase A in Living
      Cells.
AB  - Monoamine oxidase (MAO) has two isoforms, MAO-A and MAO-B, which show different
      functions, and thus selective fluorescence imaging is important for biological
      studies. Currently, however, specific detection of MAO-A remains a great
      challenge. Herein, we report a new strategy for specific imaging of MAO-A through
      the design of fluorogenic probes combining the characteristic structure of an
      inhibitor of the target enzyme along with propylamine as a recognition moiety.
      The high specificity of our representative probe is demonstrated by imaging MAO-A
      in different live cells such as SH-SY5Y (high levels of MAO-A) and HepG2 (high
      levels of MAO-B), and further validated by western blot analyses. The superior
      specificity of the probe may enable the accurate detection of MAO-A in complex
      biosystems. Importantly, the use of the characteristic structure of an inhibitor,
      as demonstrated in this work, may serve as a general strategy to design specific
      recognition moieties for fluorogenic probes for enzymes.

PMID- 29027347
TI  - A two-step evolutionary process establishes a non-native vitamin B6 pathway in
      Bacillus subtilis.
AB  - Pyridoxal 5'-phosphate (PLP), the most important form of vitamin B6 serves as a
      cofactor for many proteins. Two alternative pathways for de novo PLP biosynthesis
      are known: the short deoxy-xylulose-5-phosphate (DXP)-independent pathway, which
      is present in the Gram-positive model bacterium Bacillus subtilis and the longer
      DXP-dependent pathway, which has been intensively studied in the Gram-negative
      model bacterium Escherichia coli. Previous studies revealed that bacteria contain
      many promiscuous enzymes causing a so-called 'underground metabolism', which can
      be important for the evolution of novel pathways. Here, we evaluated the
      potential of B. subtilis to use a truncated non-native DXP-dependent PLP pathway
      from E. coli for PLP synthesis. Adaptive laboratory evolution experiments
      revealed that two non-native enzymes catalysing the last steps of the DXP
      dependent PLP pathway and two genomic alterations are sufficient to allow growth
      of vitamin B6 auxotrophic bacteria as rapid as the wild type. Thus, the existence
      of an underground metabolism in B. subtilis facilitates the generation of a
      pathway for synthesis of PLP using parts of a non-native vitamin B6 pathway. The
      introduction of non-native enzymes into a metabolic network and rewiring of
      native metabolism could be helpful to generate pathways that might be optimized
      for producing valuable substances.

PMID- 29027346
TI  - Application of stable-isotope labelling techniques for the detection of active
      diazotrophs.
AB  - Investigating active participants in the fixation of dinitrogen gas is vital as N
      is often a limiting factor for primary production. Biological nitrogen fixation
      is performed by a diverse guild of bacteria and archaea (diazotrophs), which can
      be free-living or symbionts. Free-living diazotrophs are widely distributed in
      the environment, yet our knowledge about their identity and ecophysiology is
      still limited. A major challenge in investigating this guild is inferring
      activity from genetic data as this process is highly regulated. To address this
      challenge, we evaluated and improved several 15 N-based methods for detecting N2
      fixation activity (with a focus on soil samples) and studying active diazotrophs.
      We compared the acetylene reduction assay and the 15 N2 tracer method and
      demonstrated that the latter is more sensitive in samples with low activity.
      Additionally, tracing 15 N into microbial RNA provides much higher sensitivity
      compared to bulk soil analysis. Active soil diazotrophs were identified with a 15
      N-RNA-SIP approach optimized for environmental samples and benchmarked to 15 N
      DNA-SIP. Lastly, we investigated the feasibility of using SIP-Raman
      microspectroscopy for detecting 15 N-labelled cells. Taken together, these tools
      allow identifying and investigating active free-living diazotrophs in a highly
      sensitive manner in diverse environments, from bulk to the single-cell level.

PMID- 29027348
TI  - Type VI secretion systems in plant-associated bacteria.
AB  - The type VI secretion system (T6SS) is a bacterial nanomachine used to inject
      effectors into prokaryotic or eukaryotic cells and is thus involved in both host
      manipulation and interbacterial competition. The T6SS is widespread among Gram
      negative bacteria, mostly within the Proteobacterium Phylum. This secretion
      system is commonly found in commensal and pathogenic plant-associated bacteria.
      Phylogenetic analysis of phytobacterial T6SS clusters shows that they are
      distributed in the five main clades previously described (group 1-5). The even
      distribution of the system among commensal and pathogenic phytobacteria suggests
      that the T6SS provides fitness and colonization advantages in planta and that the
      role of the T6SS is not restricted to virulence. This manuscript reviews the
      phylogeny and biological roles of the T6SS in plant-associated bacteria,
      highlighting a remarkable diversity both in terms of mechanism and function.

PMID- 29027349
TI  - Aerobic exercise training lowers platelet reactivity and improves platelet
      sensitivity to prostacyclin in pre- and postmenopausal women.
AB  - : Essentials It is unknown how regular exercise affects platelet function after
      menopause. We studied the effect of 3-months of high-intensity exercise in pre-
      and postmenopausal women. Platelet sensitivity to the inhibitory effect of
      arterially infused prostacyclin was increased. Reduced basal platelet reactivity
      was seen in the premenopausal women only. SUMMARY: Background The risk of
      atherothrombotic events increases after the menopause. Regular physical activity
      has been shown to reduce platelet reactivity in younger women, but it is unknown
      how regular exercise affects platelet function after the menopause. Objectives To
      examine the effects of regular aerobic exercise in late premenopausal and recent
      postmenopausal women by testing basal platelet reactivity and platelet
      sensitivity to prostacyclin and nitric oxide. Methods Twenty-five sedentary, but
      healthy, late premenopausal and 24 matched recently postmenopausal women, mean
      (95% confidence interval) 49.1 (48.2-49.9) and 53.7 (52.5-55.0) years old,
      participated in an intervention study: 3-month high-intensity supervised aerobic
      spinning-cycle training (1 h, * 3/week). Basal platelet reactivity was analyzed
      in platelet-rich plasma from venous blood as agonist-induced % aggregation. In a
      subgroup of 13 premenopausal and 14 postmenopausal women, platelet reactivity was
      tested ex vivo after femoral arterial infusion of prostacyclin, acetylcholine, a
      cyclooxygenase inhibitor, and after acute one-leg knee extensor exercise. Results
      Basal platelet reactivity (%aggregation) to TRAP-6 (1 MUm) was higher in the
      postmenopausal, 59% (50-68), than the premenopausal women, 45% (35-55). Exercise
      training reduced basal platelet reactivity to collagen (1 MUg mL-1 ) in the
      premenopausal women only: from 63% (55-71%) to 51% (41-62%). After the training
      intervention, platelet aggregation was more inhibited by the arterial
      prostacyclin infusion and the acute exercise in both premenopausal and
      postmenopausal women. Conclusions These results highlight previously unknown
      cardioprotective aspects of regular aerobic exercise in premenopausal and
      postmenopausal women, improving their regulation of platelet reactivity through
      an increased platelet sensitivity to prostacyclin, which may counterbalance the
      increased atherothrombotic risk associated with the menopause.

PMID- 29027350
TI  - Liposome-encapsulated chemotherapy: Current evidence for its use in companion
      animals.
AB  - Cytotoxic drugs encapsulated into liposomes were originally designed to increase
      the anticancer response, while minimizing off-target adverse effects. The first
      liposomal chemotherapeutic drug was approved for use in humans more than 20 years
      ago, and the first publication regarding its use in a canine cancer patient was
      published shortly thereafter. Regardless, no general application for liposomal
      cytotoxic drugs has been established in veterinary oncology till now. Due to the
      popularity of canines as experimental models for pharmacokinetic analyses and
      toxicity studies, multiple publications exist describing various liposomal drugs
      in healthy dogs. Also, some evidence for its use in veterinary cancer patients
      exists, especially in canine lymphoma, canine splenic hemangiosarcoma and feline
      soft tissue sarcoma, however, the results have not been overwhelming. Reasons for
      this may be related to inherent issues with the enhanced permeability and
      retention effect, the tumour phenomenon which liposomal drugs exploit. This
      effect seems very heterogeneously distributed in the tumour. Also, it is
      potentially not as ubiquitously occurring as once thought, and it may prove
      important to select patients for liposomal therapy on an individual, non
      histology-oriented, basis. Concurrently, new developments with active-release
      modified liposomes in experimental models and humans will likely be relevant for
      veterinary patients as well, and holds the potential to improve the therapeutic
      response. It, however, does not resolve the other challenges that liposomal
      chemotherapy faces, and more work still needs to be done to determine which
      veterinary patients may benefit the most from liposomal chemotherapy.

PMID- 29027351
TI  - Robotic-assisted versus open radical cystectomy in bladder cancer: A meta
      analysis of four randomized controlled trails.
AB  - BACKGROUND: Robot-assisted radical cystectomy (RARC) is increasing annually for
      treatment of bladder cancer. The objective of this meta-analysis was to compare
      the safety and efficacy of RARC and open radical cystectomy (ORC) for bladder
      cancer. METHODS: Our meta-analysis searches were conducted using PubMed, Web of
      Science, and Cochrane Library databases to identify randomized controlled trials
      (RCT) assessing the two techniques. RESULTS: Four RCT studies were identified,
      including 239 cases. Our studies indicated that RARC was associated with longer
      operative time (WMD: 69.69, 95% CI:17.25 to122.12; P= 0.009), lower estimated
      blood loss (WMD: -299.83, 95% CI:-414.66to -184.99; P<0.00001). The two groups
      had no significant difference in overall perioperative complications, length of
      hospital stay, lymph node yield and positive surgical margins. CONCLUSIONS: RARC
      is mini-invasive alternative to ORC for bladder cancer. The advantage of RARC was
      reduced estimated blood loss. More studies are needed to compare the two
      techniques.

PMID- 29027352
TI  - Impact of spontaneous donor hypothermia on graft outcomes after kidney
      transplantation.
AB  - A previous donor intervention trial found that therapeutic hypothermia reduced
      delayed graft function (DGF) after kidney transplantation. This retrospective
      cohort study nested in the randomized dopamine trial (ClinicalTrials.gov
      identifier: NCT000115115) investigates the effects of spontaneous donor
      hypothermia (core body temperature <36 degrees C) on initial kidney graft
      function, and evaluates 5-year graft survival. Hypothermia assessed by a singular
      measurement in the intensive care unit 4-20 hours before procurement was
      associated with less DGF after kidney transplantation (odds ratio [OR] 0.56, 95%
      confidence interval [CI] 0.34-0.91). The benefit was greater when need for more
      than a single posttransplant dialysis session was analyzed (OR 0.48, 95%CI 0.28
      0.82). Donor dopamine ameliorated dialysis requirement independently from
      hypothermia in a temporal relationship with exposure (OR 0.93, 95%CI 0.87-0.98,
      per hour). A lower core body temperature in the donor was associated with lower
      serum creatinine levels before procurement, which may reflect lower systemic
      inflammation and attenuated renal injury from brain death. Despite a considerable
      effect on DGF, our study failed to demonstrate a graft survival advantage (hazard
      ratio [HR] 0.83, 95%CI 0.54-1.27), whereas dopamine treatment was associated with
      improved long-term outcome (HR 0.95, 95%CI 0.91-0.99 per hour).

PMID- 29027353
TI  - Early predictors of mortality in children with pulmonary complications after
      haematopoietic stem cell transplantation.
AB  - PC are a main cause of death following HSCT in children. We aimed to evaluate
      early predictors of mortality in paediatric recipients with PCs. A retrospective
      observational study of 35 patients with 49 episodes of PI on chest radiography
      (of 124 patients) who had undergone HSCT at a tertiary university hospital
      between January 2011 and December 2012 was performed. During follow-up (median
      26.1 months), 15 episodes led to death (30.6%). An aetiologic diagnosis was made
      by non-invasive tests in 24 episodes (49.0%) and by adding bronchoalveolar lavage
      and/or lung biopsy in 7 episodes with diagnostic yield (77.8%, P = .001). Thus, a
      specific diagnosis was obtained in 63.3% of the episodes. Aetiology
      identification and treatment modification after diagnosis did not decrease
      mortality (P = .057, P = .481). However, the number of organ dysfunctions at the
      beginning of PI was higher in the mortality group, compared to the survivor group
      (1.7 +/- 1.2 vs 0.32 +/- 0.59; P = .001). Hepatic dysfunction (OR, 11.145; 95%
      CI, 1.23 to 101.29; P = .032) and neutropaenia (OR, 10.558; 95% CI, 1.07 to
      104.65; P = .044) were independently associated with risk of mortality.
      Therefore, hepatic dysfunction and neutropaenia are independent early predictors
      of mortality in HSCT recipients with PCs.

PMID- 29027354
TI  - Propensity to match or mismatch patients and therapies?

PMID- 29027355
TI  - A descriptive analysis of rabies post-exposure prophylaxis data: 2013, Ontario,
      Canada.
AB  - By 2013, the number of confirmed rabid animals in Ontario had decreased to
      unprecedented low numbers, yet the expected decrease in the number of courses of
      rabies post-exposure prophylaxis (RPEP) administered did not occur consistent
      with the decrease in animal rabies cases (Figure ). This prompted a review of the
      reasons that RPEP was administered in Ontario. This study provides a descriptive
      analysis of the exposure incidents resulting in RPEP administration in Ontario
      during 2013 using data obtained from the integrated Public Health Information
      System, a Web-based disease surveillance system. Findings from the study revealed
      that the number of RPEP courses administered could be reduced, without increased
      risk of rabies, through the following strategies: (i) Education and resources for
      public health staff and healthcare providers who assess animal exposures to
      improve interpretation of guidelines for RPEP administration. (ii) Refinement of
      guidelines for public health staff and healthcare providers to ensure that they
      support detailed consideration of the circumstances of the exposure in order to
      assist with the risk assessment. Guidelines should also support completion of a
      risk assessment when exposures to skunks, foxes, raccoons and other wild
      carnivores are provoked by the victim, as opposed to automatically providing RPEP
      as recommended by current guidelines. (iii) Public education strategies to
      prevent exposures to animals (e.g., do not touch unattended animals, bat proofing
      your house, proper removal of bats from the house). (iv) Defining the criteria to
      declare a jurisdiction rabies-free. (v) Exploring strategies to improve
      surveillance for rabid animals.

PMID- 29027356
TI  - Relationship between neighborhood socioeconomic status and venous
      thromboembolism: results from a population-based study.
AB  - : Essentials Literature on socioeconomic status (SES) and incidence of venous
      thromboembolism (VTE) is scarce. We assessed neighborhood SES with VTE risk in a
      population of over 1.4 million inhabitants. Higher neighborhood SES was
      associated with lower incidence of VTE. These findings are helpful to inform
      policy and resource allocation in health systems. SUMMARY: Background The
      association between socioeconomic status and arterial cardiovascular disease is
      well established. However, despite its high burden of disability-adjusted life
      years, little research has been carried out to determine whether socioeconomic
      status is associated with venous thromboembolism. Objective To determine if
      neighborhood socioeconomic status is associated with venous thromboembolism in a
      population-based study from the Netherlands. Methods We identified all patients
      aged 15 years and older with a first event of venous thromboembolism from
      inhabitants who lived in the urban districts of The Hague, Leiden and Utrecht in
      the Netherlands in 2008-2012. Neighborhood socioeconomic status was based on the
      status score, which combines educational level, income and unemployment on a four
      digit postal code level. Incidence rate ratios of venous thromboembolism were
      calculated for different levels of neighborhood socioeconomic status, with
      adjustments for age and sex. Results A total of 7373 patients with a first venous
      thromboembolism (median age 61 years; 50% deep vein thrombosis) were identified
      among more than 1.4 million inhabitants. Higher neighborhood SES was associated
      with lower incidence of VTE. In the two highest status score groups (i.e. the 95
      99th and > 99th percentile), the adjusted incidence rate ratios were 0.91 (95%
      confidence interval [CI], 0.84-1.00) and 0.80 (95% CI, 0.69-0.93), respectively,
      compared with the reference status score group (i.e. 30-70th percentile).
      Conclusions High neighborhood socioeconomic status is associated with a lower
      risk of first venous thromboembolism.

PMID- 29027357
TI  - Studies on the aerobic utilization of synthesis gas (syngas) by wild type and
      recombinant strains of Ralstonia eutropha H16.
AB  - The biotechnical platform strain Ralstonia eutropha H16 was genetically
      engineered to express a cox subcluster of the carboxydotrophic Oligotropha
      carboxidovoransOM5, including (i) the structural genes coxM, -S and -L, coding
      for an aerobic carbon monoxide dehydrogenase (CODH) and (ii) the genes coxD, -E, 
      F and -G, essential for the maturation of CODH. The coxOc genes expressed under
      control of the CO2 -inducible promoter PL enabled R. eutropha to oxidize CO to
      CO2 for the use as carbon source, as demonstrated by 13 CO experiments, but the
      recombinant strains remained dependent on H2 as external energy supply.
      Therefore, a synthetic metabolism, which could be described as
      'carboxyhydrogenotrophic', was established in R. eutropha. With this extension of
      the bacterium's substrate range, growth in CO-, H2 - and CO2 -containing
      artificial synthesis gas atmosphere was enhanced, and poly(3-hydroxybutyrate)
      synthesis was increased by more than 20%.

PMID- 29027358
TI  - Assessment of the inferior mesenteric vein diameter as a surrogate marker to
      evaluate response to neoadjuvant chemoradiotherapy for locally advanced rectal
      adenocarcinoma.

PMID- 29027359
TI  - A master manipulator with a remote-center-of-motion kinematic structure for a
      minimally invasive robotic surgical system.
AB  - BACKGROUND: In robotic surgical systems, commercial master devices have
      limitations owing to insufficient workspace and lack of intuitiveness. To
      overcome these limitations, a remote-center-of-motion (RCM) master manipulator
      was proposed. METHODS: The feasibility of the proposed RCM structure was
      evaluated through kinematic analysis using a conventional serial structure. Two
      performance comparison experiments (peg transfer task and objective transfer
      task) were conducted for the developed master and Phantom Omni. RESULTS: The
      kinematic analysis results showed that compared with the serial structure, the
      proposed RCM structure has better performance in terms of design efficiency (19%)
      and workspace quality (59.08%). Further, in comparison with Phantom Omni, the
      developed master significantly increased task efficiency and significantly
      decreased workload in both experiments. CONCLUSIONS: The comparatively better
      performance in terms of intuitiveness, design efficiency, and operability of the
      proposed master for a robotic system for minimally invasive surgery was confirmed
      through kinematic and experimental analysis.

PMID- 29027360
TI  - Preparation of hydrophilic blood compatible polypropylene/pluronics F127 films.
AB  - In order to improve surface hydrophilicity, blood compatibility and cell
      antiadhesion of polypropylene (PP) film, polypropylene oxide (PPO)-polyethylene
      oxide-PPO used as macromolecular surface modifier through physical blending.
      Surface properties of blended PP/Pluronic F127 (PF127) samples were investigated
      by attenuated total reflection infrared spectroscopy and water contact angle
      measurements. Results demonstrated that PF127 migrated to the surface. Thus,
      mechanical properties of blended PP/PF127 samples with the aim of the revealing
      the effects of the presence of modifier in the bulk were investigated through
      differential scanning calorimetry, X-ray diffraction, and tensile tests. The
      biocompatibility and hemocompatibility of modified PP films were evaluated by 3
      (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, platelet
      rich plasma, and hemolysis tests. These results showed excellent anticell and
      antiplatelet adhesion which deems the prepared blended films proper biomaterials.
      (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 652-662, 2018.

PMID- 29027361
TI  - Magnetic molecularly imprinted polymers for recognition and enrichment of
      polysaccharides from seaweed.
AB  - New magnetic molecularly imprinted polymers with two templates were fabricated
      for the recognition of polysaccharides (fucoidan and alginic acid) from seaweed
      by magnetic solid-phase extraction, and the materials were modified by seven
      types of deep eutectic solvents. It was found that the deep eutectic solvents
      magnetic molecularly imprinted polymers showed stronger recognition and higher
      recoveries for fucoidan and alginic acid than magnetic molecularly imprinted
      polymers, and the deep eutectic solvents-4-magnetic molecularly imprinted
      polymers had the best effects. The practical recovery of the two polysaccharides
      (fucoidan and alginic acid) purified with deep eutectic solvents-4-magnetic
      molecular imprinted polymers in seaweed under the optimal conditions were 89.87,
      and 92.0%, respectively, and the actual amounts extracted were 20.6 and 18.7
      MUg/g, respectively. To sum up, the developed method proved to be a novel and
      promising method for the recognition of complex polysaccharide samples from
      seaweed.

PMID- 29027362
TI  - Impact of Extraction Methods on the Detectable Protein Complement of
      Metaproteomic Analyses of Marine Sediments.
AB  - Metaproteomic analysis targets proteins, the catalytic entities in the habitat,
      thereby providing direct insights into the metabolic activity of the community
      studied. A major challenge still remaining for metaproteomics is the effective
      and comprehensive extraction of proteins from environmental samples, due to their
      high complexity with respect to organismic diversity and abundance range.
      Moreover, in certain habitats, the inherent matrix may interfere with protein
      extraction. In recent years, several studies reported different protein
      extraction methods for soils known for their complex geochemistry, but only three
      analyzed marine sediments that generally comprise different though similarly
      complex geochemistry. In this study, the impact of four different extraction
      methods was investigated for coastal North Sea and deep sea Pacific Ocean
      sediments. The extraction methods comprised (i) phenol, (ii) SDS, (iii) a mixture
      of SDS and phenol, and (iv) urea and thiourea. Prior to extraction, a cell and
      protein standard (CPS) was added to the sediment samples to trace recovery of
      proteins from different subcellular locations as well as dissolved BSA. While
      each extraction method detected distinct peptide complements, SDS-phenol
      extraction generally achieved highest protein yield and most comprehensive CPS
      protein identification. Application of two different methods was shown to further
      improve proteome coverage.

PMID- 29027364
TI  - A functional polymorphism of the OXTR gene is associated with autistic traits in
      Caucasian and Asian populations.
AB  - There is increasing evidence for associations between polymorphisms of the
      oxytocin receptor (OXTR) gene and autism spectrum disorder, but to date no study
      has established links with autistic traits in healthy subjects and potential
      cultural differences. The present research firstly investigated associations
      between three widely studied OXTR SNPs and autistic and empathic traits (rs53576
      (G/A); rs2254298 (G/A); rs2268498 (T/C)) in two independent studies on male and
      female Caucasian (n = 537) and Chinese students (n = 280). Autistic and empathic
      traits were measured in all subjects in the two independent groups using the
      Autism -Spectrum Quotient (AQ) and the Interpersonal Reactivity Index (IRI)
      respectively, together with their sub-scales. For both sites, genotyping of the
      OXTR SNPs was conducted on buccal swab samples using a Cobas Z 480 Light Cycler
      following automated DNA extraction. Associations at the genotype level with
      autism trait scores were found in Caucasian subjects for rs2268498 only, with TT
      carriers having the lowest AQ scores compared with those carrying at least one C
      allele. This finding was independently replicated in the Chinese sample although
      a smaller proportion carried the C-allele compared with the Caucasian sample.
      Some minor associations were found between empathy trait scores and the three
      SNPs but were not consistent between the samples. These findings show for the
      first time that the rs2268498 SNP localized in the promoter flanking region of
      the OXTR gene is associated with autistic traits in different ethnic/cultural
      groups. This provides further support for the role of the OXTR gene in relation
      to autism.

PMID- 29027365
TI  - Reply to Akingboye et al.

PMID- 29027366
TI  - Collaborative research among academia, business, and government.

PMID- 29027363
TI  - Optimizing separations in online comprehensive two-dimensional liquid
      chromatography.
AB  - Online comprehensive two-dimensional liquid chromatography has become an
      attractive option for the analysis of complex nonvolatile samples found in
      various fields (e.g. environmental studies, food, life, and polymer sciences).
      Two-dimensional liquid chromatography complements the highly popular hyphenated
      systems that combine liquid chromatography with mass spectrometry. Two
      dimensional liquid chromatography is also applied to the analysis of samples that
      are not compatible with mass spectrometry (e.g. high-molecular-weight polymers),
      providing important information on the distribution of the sample components
      along chemical dimensions (molecular weight, charge, lipophilicity,
      stereochemistry, etc.). Also, in comparison with conventional one-dimensional
      liquid chromatography, two-dimensional liquid chromatography provides a greater
      separation power (peak capacity). Because of the additional selectivity and
      higher peak capacity, the combination of two-dimensional liquid chromatography
      with mass spectrometry allows for simpler mixtures of compounds to be introduced
      in the ion source at any given time, improving quantitative analysis by reducing
      matrix effects. In this review, we summarize the rationale and principles of two
      dimensional liquid chromatography experiments, describe advantages and
      disadvantages of combining different selectivities and discuss strategies to
      improve the quality of two-dimensional liquid chromatography separations.

PMID- 29027367
TI  - The parasporal crystals of Bacillus pumilus strain 15.1: a potential virulence
      factor?
AB  - Bacillus pumilus strain 15.1 was previously found to cause larval mortality in
      the Med-fly Ceratitis capitata and was shown to produce crystals in association
      with the spore. As parasporal crystals are well-known as invertebrate-active
      toxins in entomopathogenic bacteria such as Bacillus thuringiensis (Cry and Cyt
      toxins) and Lysinibacillus sphaericus (Bin and Cry toxins), the B. pumilus
      crystals were characterized. The crystals were composed of a 45 kDa protein that
      was identified as an oxalate decarboxylase by peptide mass fingerprinting, N
      terminal sequencing and by comparison with the genome sequence of strain 15.1.
      Synthesis of crystals by a plasmid-cured derivative of strain 15.1 (produced
      using a novel curing strategy), demonstrated that the oxalate decarboxylase was
      encoded chromosomally. Crystals spontaneously solubilized when kept at low
      temperatures, and the protein produced was resistant to trypsin treatment. The
      insoluble crystals produced by B. pumilus 15.1 did not show significant toxicity
      when bioassayed against C. capitata larvae, but once the OxdD protein was
      solubilized, an increase of toxicity was observed. We also demonstrate that the
      OxdD present in the crystals has oxalate decarboxylate activity as the formation
      of formate was detected, which suggests a possible mechanism for B. pumilus 15.1
      activity. To our knowledge, the characterization of the B. pumilus crystals as
      oxalate decarboxylase is the first report of the natural production of parasporal
      inclusions of an enzyme.

PMID- 29027368
TI  - Expression of fluorescent proteins in Lactobacillus rhamnosus to study host
      microbe and microbe-microbe interactions.
AB  - Probiotic Lactobacillus strains are widely used to benefit human and animal
      health, although the exact mechanisms behind their interactions with the host and
      the microbiota are largely unknown. Fluorescent tagging of live probiotic cells
      is an important tool to unravel their modes of action. In this study, the
      implementation of different heterologously expressed fluorescent proteins for the
      labelling of the model probiotic strains Lactobacillus rhamnosusGG
      (gastrointestinal) and Lactobacillus rhamnosusGR-1 (vaginal) was explored.
      Heterologous expression of mTagBFP2 and mCherry resulted in long-lasting
      fluorescence of L. rhamnosusGG and GR-1 cells, using the nisin-controlled
      expression (NICE) system. These novel fluorescent strains were then used to study
      in vitro aspects of their microbe-microbe and microbe-host interactions.
      Lactobacillus rhamnosusGG and L. rhamnosusGR-1 expressing mTagBFP2 and mCherry
      could be visualized in mixed-species biofilms, where they inhibited biofilm
      formation by Salmonella Typhimurium-gfpmut3 expressing the green fluorescent
      protein. Likewise, fluorescent L. rhamnosusGG and L. rhamnosusGR-1 were
      implemented for the visualization of their adhesion patterns to intestinal
      epithelial cell cultures. The fluorescent L. rhamnosus strains developed in this
      study can therefore serve as novel tools for the study of probiotic interactions
      with their environment.

PMID- 29027369
TI  - Range of therapeutic prothipendyl and prothipendyl sulfoxide concentrations in
      clinical blood samples.
AB  - Due to a lack of reference blood concentrations in the literature, the forensic
      evaluation of prothipendyl findings in blood samples is difficult.
      Interpretations with regard to the assessment of blood concentrations as well as
      an estimation of the ingested prothipendyl amounts were often vague. To describe
      a concentration range in clinical samples, prothipendyl and prothipendyl
      sulfoxide concentrations were determined in serum samples of 50 psychiatric
      patients receiving 40 mg, 80 mg, or 160 mg doses of prothipendyl. The analyses of
      prothipendyl and prothipendyl sulfoxide were carried out using validated methods
      of high performance liquid chromatography coupled to triple quadrupole mass
      spectrometry (LC-QQQ-MS), respectively. 40 mg doses caused average prothipendyl
      serum concentrations of 18.0 ng/mL (1 hour after intake) and 7.9 ng/mL (10.5
      hours after intake), while 80 mg doses caused averages of 42.6 ng/mL and 15.2
      ng/mL at the mentioned times of sampling. Irrespective of the given dose,
      prothipendyl concentrations below 30 ng/mL were observed in 80% of the patient
      samples taken 1 hour after ingestion as well as in 90% of the samples collected
      10.5 hours after administration. Serum concentrations of the Phase I metabolite
      prothipendyl sulfoxide averaged 4.3 ng/mL (1 hour after intake) and 3.6 ng/mL
      (10.5 hours after intake). Possible drug-drug interactions regarding absorption
      and metabolism of prothipendyl are discussed. Results of the herein presented
      study are useful for the interpretation of analytical prothipendyl findings in
      forensic toxicology. The utility of the described concentration range is
      demonstrated by discussing two death cases involving prothipendyl findings.

PMID- 29027370
TI  - Molecular detection of hepatitis E virus in wild boar population in eastern
      Romania.
AB  - In industrialized countries, Hepatitis E is a recognized zoonosis, with wild boar
      and swine representing the main reservoirs for zoonotic genotype HEV-3 in Europe.
      Data related to HEV infection in wild boar population in Romania are restricted
      to serological surveys. Therefore, our main goal was to determine the HEV
      prevalence in wild boar population and to characterize HEV strains circulating in
      Romania. Using TaqMan real-time RT-PCR assay, we analyzed the presence of RNA HEV
      in 45 liver samples and five spleen samples collected from 50 wild boars. Samples
      were collected during the 2013-2015 hunting seasons. Nine samples of 50 were
      tested positive for HEV RNA, resulting an overall prevalence of 18%. Phylogenetic
      analysis revealed that the isolates clustered in different HEV-3 monophyletic
      groups, depending on the sampling county. This is the first study signalling,
      based on molecular analysis, the presence of HEV in wild boar population from
      Romania. Also, in this study, we report the detection of HEV in splenic tissue
      from wild boar.

PMID- 29027371
TI  - Differential Proteomic Analysis of Dimethylnitrosamine (DMN)-Induced Liver
      Fibrosis.
AB  - Liver fibrosis is a common pathological feature of many chronic liver diseases.
      To characterize the entire panorama of proteome changes in dimethylnitrosamine
      (DMN)-induced liver fibrosis, isobaric tags for relative and absolute
      quantitation (iTRAQ)-based differential proteomic analysis is performed with DMN
      induced liver fibrosis rats. A total of 4155 confidently identified proteins are
      found, with 365 proteins showing significant changes (fold changes of >1.5 or <
      0.67, p < 0.05). In metabolic activation, proteins assigned to drug metabolism
      enzymes (e.g., CYP2D1) change, suggesting that the liver protection mechanism is
      activated to relieve DMN toxicity. In addition, the altered proteins of immune
      response and oxidative stress may activate hepatic stellate cells. Glucose
      metabolism disorder in DMN model rats is demonstrated by a decrease in key
      enzymes (e.g., ACSL1) in fatty acid metabolism, a tricabolic acid cycle-related
      enzyme (SDH), glycogenolysis enzyme, and gluconeogenesis enzymes (PC, PCKGC) and
      by an increase in glycolysis enzymes (e.g., HXK1). Meanwhile, alterations in iron
      and calcium ion homeostasis proteins are observed. Our results also show that
      mitochondrial dysfunction may be involved in DMN hepatotoxicity. In conclusion,
      these altered liver proteins in the DMN model and control rats provide data for
      understanding the functional mechanism of liver fibrosis.

PMID- 29027373
TI  - To MB/PhD or not to MB/PhD.

PMID- 29027372
TI  - Full-Genome Sequence of Porcine Circovirus type 3 recovered from serum of sows
      with stillbirths in Brazil.
AB  - Two full-genome sequences of porcine circovirus type 3 (PCV3) are reported. The
      genomes were recovered from pooled serum samples from sows who had just delivered
      litters with variable numbers of stillbirths. The two circular genomes (PCV3
      BR/RS/6 and PCV3-BR/RS/8) are 2,000 nucleotides long and contain two open reading
      frames (ORFs) oriented in opposite directions that encode the putative capsid
      (Cap) and replicase (Rep) proteins. The intergenic region contains a stem-loop
      motif, as reported for other circoviruses. Rolling circle replication motifs and
      putative helicase domains were identified in the Rep coding region. The degree of
      overall nucleotide similarity between the genomes reported here and those
      available at GenBank was higher than 97%. No PCV3 sequence was detected in pooled
      serum samples from sows which had no stillbirths on the same farms. However,
      further studies are necessary to confirm the association between PCV3 and the
      occurrence of stillbirths.

PMID- 29027374
TI  - Flow cytometric monitoring of bacterioplankton phenotypic diversity predicts high
      population-specific feeding rates by invasive dreissenid mussels.
AB  - Species invasion is an important disturbance to ecosystems worldwide, yet
      knowledge about the impacts of invasive species on bacterial communities remains
      sparse. Using a novel approach, we simultaneously detected phenotypic and derived
      taxonomic change in a natural bacterioplankton community when subjected to
      feeding pressure by quagga mussels, a widespread aquatic invasive species. We
      detected a significant decrease in diversity within 1 h of feeding and a total
      diversity loss of 11.6 +/- 4.1% after 3 h. This loss of microbial diversity was
      caused by the selective removal of high nucleic acid populations (29 +/- 5% after
      3 h). We were able to track the community diversity at high temporal resolution
      by calculating phenotypic diversity estimates from flow cytometry (FCM) data of
      minute amounts of sample. Through parallel FCM and 16S rRNA gene amplicon
      sequencing analysis of environments spanning a broad diversity range, we showed
      that the two approaches resulted in highly correlated diversity measures and
      captured the same seasonal and lake-specific patterns in community composition.
      Based on our results, we predict that selective feeding by invasive dreissenid
      mussels directly impacts the microbial component of the carbon cycle, as it may
      drive bacterioplankton communities toward less diverse and potentially less
      productive states.

PMID- 29027375
TI  - Vibrio vulnificus: new insights into a deadly opportunistic pathogen.
AB  - Vibrio vulnificus is a Gram-negative aquatic bacterium first isolated by the
      United States (US) Centers for Disease Control and Prevention (CDC) in 1964. This
      bacterium is part of the normal microbiota of estuarine waters and occurs in high
      numbers in molluscan shellfish around the world, particularly in warmer months.
      Infections in humans are derived from consumption of seafood produce and from
      water exposure. Vibrio vulnificus is a striking and enigmatic human pathogen, yet
      many aspects related to its biology, genomics, virulence capabilities and
      epidemiology remain elusive and poorly understood. This pathogen is responsible
      for over 95% of seafood-related deaths in the United States, and carries the
      highest fatality rate of any food-borne pathogen. Indeed, infections associated
      with this pathogen that progress to primary septicaemia have a similar case
      fatality rate to category BSL 3 and 4 pathogens, such as anthrax, bubonic plague,
      Ebola and Marburg fever. Interestingly, V. vulnificus infections
      disproportionately affect males (~85% of cases) and older patients (> 40 years),
      especially those with underlying conditions such as liver diseases, diabetes and
      immune disorders. New insights from molecular studies and comparative genomic
      approaches have offered tantalising insights into this pathogen. A recent
      increase and geographical spread in reported infections, in particular wound
      cases, underlines the growing international importance of V. vulnificus,
      particularly in the context of coastal warming. We outline and explore here a
      range of current data gaps regarding this important pathogen, and provide some
      current thoughts on approaches to elucidate key aspects associated with this
      bacterium.

PMID- 29027376
TI  - Adenosine A2A receptor agonist ameliorates EAE and correlates with Th1 cytokine
      induced blood brain barrier dysfunction via suppression of MLCK signaling
      pathway.
AB  - INTRODUCTION: Multiple sclerosis (MS) disease activity is associated with blood
      brain barrier (BBB) disruption, which is mediated by inflammatory cytokines
      released by CD4+ lymphocytes. To assess the effects of adenosine A2A receptors on
      BBB permeability in vitro and in vivo. METHODS: A2A receptor expression was
      detected by immunostaining in experimental autoimmune encephalomyelitis (EAE)
      C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG)35-55 , and
      human MS brain. F-actin and the tight junction protein Claudin-5 were assessed in
      endothelial cells treated with an A2A receptor specific agonist (CGS-21680) after
      Th1 cytokine stimulation. EAE mice were divided into control and CGS-21680 (50
      ug/kg, i.p., daily) groups. Disease scores were recorded daily to evaluate
      neurological impairment. The effects of A2A receptor on inflammation and
      demyelination were assessed after euthanasia by immunostaining or histology; BBB
      permeability was measured by sodium fluoride (Na-F) and FITC-dextran amounts.
      RESULTS: Endothelial A2A receptor was detected in demyelination areas of MS brain
      samples. In EAE lesions, A2A receptor was expressed in the endothelium in
      association with immune cell infiltration. Treatment with CGS-21680 counteracted
      the effects of Th1 cytokines on endothelial cells in vitro, preventing the
      reduction of tight junction protein expression and stress fiber formation. The
      effects of A2A receptor activation were correlated with MLCK phosphorylation
      signaling repression. In EAE, A2A receptor agonist decreased BBB permeability and
      inhibited EAE neurologic deficiency in mice. CONCLUSIONS: A2A receptor activation
      at EAE onset helps reduce the effects of Th1 stimulation on BBB permeability,
      indicating that A2A receptor mediates BBB function in CNS demyelinated disease.

PMID- 29027377
TI  - Contribution of Extracellular Matrix and Signal Mechanotransduction to Epithelial
      Cell Damage in Inflammatory Bowel Disease Patients: A Proteomic Study.
AB  - This study utilizes 2D-DIGE (difference gel etrophoresis), isotope-coded protein
      labeling and biochemical assays to characterize protein alteration in ulcerative
      colitis (UC) and Crohn's disease (CD) in human epithelial cell and mucosal
      biopsies in inflammatory bowel disease (IBD)-affected patients. The aim of this
      study is to identify the key molecular signatures involved in epithelial cell
      structure of IBDs. In non-inflamed UC (QUC) keratins, vimentin, and focal
      adhesion kinase (7) increased, whereas vinculin and de-tyrosinated alpha-tubulin
      decreased; inflammation (IUC) exacerbated molecular changes, being collagen type
      VI alpha 1 chain (COL6A1), tenascin-C and vimentin increased. In non-inflamed CD
      (QCD), tenascin C, de-tyrosinated alpha-tubulin, vinculin, FAK, and Rho
      associated protein kinase 1 (ROCK1) decreased while vimentin increased. In
      inflamed CD (ICD), COL6A1, vimentin and integrin alpha 4 increased. In QUC, cell
      metabolism is characterized by a decrease of the tricarboxylic acid cycle enzymes
      and a decrease of short/branched chain specific acyl-CoA dehydrogenase, fatty
      acid synthase, proliferator-activated receptors alpha, and proliferator-activated
      receptors gamma. In QCD a metabolic rewiring occurs, as suggested by glycerol-3
      phosphate dehydrogenase (GPD2), pyruvate dehydrogenase E1 component subunit beta,
      NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, and 4
      trimethylaminobutyraldehyde dehydrogenase increment, while dihydrolipoyl
      dehydrogenase decreased. Macroautophagy is activated in QUC and IUC, with
      increased levels of p62, HSC70, major vault protein, myosin heavy chain 9,
      whereas it is blunted in QCD and ICD. The differing pattern of extracellular
      matrix, cytoskeletal derangements, cellular metabolism, and autophagy in UC and
      CD may contribute to the pathophysiological understanding of these disorders and
      serve as diagnostic markers in IBD patients.

PMID- 29027378
TI  - Why is African swine fever still present in Sardinia?
AB  - African swine fever (ASF) is an infectious disease of swine that has been present
      in Sardinia since 1978. Soon after introduction of the disease, several control
      and eradication programmes were established with limited success. Some
      researchers attributed the persistence of the disease in central and eastern
      areas to certain socio-economic factors, the existence of some local and
      traditional farming practices (i.e., unregistered free-ranging pigs known as
      brado animals) and the high density of wild boar in the region. In the past,
      scarcity of swine data in Sardinia complicated the evaluation and study of ASF on
      the island. More complete, accurate and reliable information on pig farms has
      become available as a result of the most recent eradication programmes. Here, we
      perform statistical modelling based on these data and the known distribution of
      domestic pig and wild boar to identify the main risk factors that have caused ASF
      persistence in Sardinia. Our results categorized, identified and quantified nine
      significant risk factors, six of which have not been previously described. The
      most significant factors were the number of medium-sized farms, the presence of
      brado animals and the combination of estimated wild boar density and mean
      altitude above sea level. Based on these factors, we identified regions in
      eastern and central Sardinia to be at greatest risk of ASF persistence; these
      regions are also where the disease has traditionally been endemic. Based on these
      risk factors, we propose specific control measures aimed at mitigating such risks
      and eradicating ASF from the island.

PMID- 29027379
TI  - Impact of omalizumab in children from a middle-income country with severe therapy
      resistant asthma: A real-life study.
AB  - BACKGROUND: Severe asthma in children is a global health problem. Severe therapy
      resistant asthma (STRA) in children is a major clinical challenge due to
      persistent symptoms despite high doses of corticosteroids and results in high
      public health costs. Omalizumab (anti-IgE monoclonal antibody) has been described
      as an effective add-on therapy in these patients. The characteristics of children
      with STRA from low- and middle-income countries have scarcely been reported, and
      no real-life study has been published on the effects of omalizumab in this group
      of patients. The aim of our study is to report the first clinical real-life
      experiences with omalizumab in Brazilian children with STRA. METHODS: Children (6
      18 years old) from a referral center who were diagnosed with STRA were included
      in this retrospective study based on our clinical databases. The included
      children had undergone at least 6 months of omalizumab treatment and fulfilled
      the following initial criteria: 1) >6 years old; 2) a positive skin-prick test
      for at least one aeroallergen; and 3) a serum total IgE level between 30 and 1500
      IU/mL. Clinical and lung function variables were analyzed before and after
      treatment. RESULTS: Fourteen children (mean age: 11.9 years; percentage female:
      72%) were included in this study. Omalizumab treatment significantly increased
      control of the disease according to a standardized questionnaire administered at
      every visit (P < 0.0001), ceased hospitalizations in 70% (P = 0.02) of patients,
      and allowed 8/9 (89%) patients to be weaned off oral steroids (P = 0.004).
      CONCLUSIONS: In this retrospective report, the use of omalizumab in Brazilian
      children with STRA significantly improved disease control, decreased
      hospitalizations, and allowed suspension of continuous oral corticosteroids.

PMID- 29027380
TI  - Different expression about induced sputum cell sorting in the two main types of
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: The difference in expression of sputum cells types between the two
      main types of chronic obstructive pulmonary disease (COPD) is largely unknown.
      This study aims to investigate the difference and then wants to depend on sputum
      cells sorting to direct the treatment of COPD. METHODS: A total of 218 patients
      with stable COPD (FEV1 < 80%) were selected. Stable COPD patients (n = 218) were
      classified as eosinophilic (A phenotype) or noneosinophilic (B phenotype);
      sometimes, the subjects were separated into cough group (C phenotype) and dyspnea
      group (D phenotype). Cross-sectional analysis was conducted comparing
      demographics and clinical characteristics. Receiver-operating characteristic
      curve was used to assess predictive ability of sputum eosinophils for D
      phenotype. RESULTS: The A phenotype showed a higher correlation with the patients
      complaining of presenting with dyspnea on exertion, the dyspnea group (D
      phenotype). The B phenotype showed a higher prevalence of those who cough and
      product sputum, this was cough group (C phenotype). Sputum eosinophil and
      macrophages counts were significantly higher in patients with dyspnea (n = 95)
      compared to those with cough (P < .05), and neutrophils were significantly lower
      in patients with dyspnea (n = 95) compared to those with cough (P < .05).
      Percentage sputum eosinophil count was predictive of dyspnea (D phenotype) COPD
      with area under curve (AUC) of 0.831 (95% confidence interval (CI) 0.77-0.89; P
      <= .001). Neutrophils were also predictive of dyspnea (D phenotype) COPD with AUC
      of 0.276 (95% CI 0.204-0.347; P <= .001). CONCLUSION: These findings suggest that
      the morphological phenotypes of COPD show several clinical characteristics and
      different sputum cell sorting.

PMID- 29027381
TI  - Evaluation of a new energy device for parenchymal transection in laparoscopic
      liver resection.
AB  - INTRODUCTION: THUNDERBEAT (TB) is a novel device that uses both ultrasonic and
      advanced bipolar energies for hemostasis. Several recent human studies have
      proved the safety and efficacy of TB in different surgical procedures, but there
      have been no similar studies about its efficacy in hepatic parenchymal
      transection. Therefore, the aim of the study was to assess the safety and
      efficacy of the TB device in laparoscopic liver resection. METHODS: This
      retrospective study compared TB and ultrasonic Harmonic devices in 80 patients
      who underwent laparoscopic liver resection from 2010 to 2016 in our institution.
      To reduce the selection bias, the two groups were matched in a 1-to-2 ratio on
      the basis of propensity scores. RESULTS: There were no differences in the
      preoperative patient characteristics between the two groups. The extent of liver
      resection was comparable between the groups. Although the Harmonic group's
      intraoperative blood loss and operative time were less than that of the TB group,
      the differences were not statistically significant (P = 0.08, P = 0.32,
      respectively). Postoperative complications, mortality within 90 days, and
      hospital stay were comparable between the two groups. CONCLUSION: TB is as safe
      and effective for parenchymal transection in laparoscopic hepatectomy as
      ultrasonic devices, but it is not a superior alternative.

PMID- 29027382
TI  - Antibiotic resistance in the most unlikeliest of places.

PMID- 29027384
TI  - Survey for Correlation between Biofilm Formation and Virulence Determinants in a
      Collection of Pathogenic and Fecal Enterococcus faecalis Isolates.
AB  - BACKGROUND: Enterococcus faecalis is an opportunistic pathogen that causes most
      of the enterococcal infections. Among the different factors implicated in the
      pathogenesis of these organisms, biofilm formation and antibiotic resistance are
      the most important. The ability for biofilm formation has been attributed to the
      presence of some virulence genes. However, no definite correlation has been
      found. This study aimed to detect biofilm formation and antibiotic resistance
      patterns in E. faecalis isolates collected from clinical and fecal samples, and
      to investigate possible correlation between some virulence genes (esp, cyl, gelE)
      and biofilm formation. MATERIALS AND METHODS: A collection of 123 E. faecalis
      isolates were investigated for antibiotic resistance and production of hemolysin,
      gelatinase, and biofilm using phenotypic methods. The esp, gelE and cyl genes
      were detected using polymerase chain reaction. RESULTS: Thirty-eight pathogenic
      isolates (37%) were positive for biofilm formation. Additionally, the gelE, esp,
      and cyl genes were detected in 74 (71.8%), 79 (76.7%) and 42 (40.8%) isolates,
      respectively. In the fecal samples, 18 (90%) isolates were biofilm producers and
      11 (55%), 17 (85%) and 8 (40%) isolates were positive for gelE, esp, and cyl,
      respectively. There were significant differences in biofilm production between
      pathogenic and fecal isolates (P <0.001). Multidrug resistance (MDR) was found
      among 32% (n = 33) and 15% (n = 3) of the clinical and fecal isolates,
      respectively. However, no significant difference was seen between MDR and biofilm
      formation. Five pathogenic and two fecal isolates were negative for all
      investigated genes while they were they were biofilm producers. In contrast, 22
      pathogenic isolates and 1 fecal isolate were positive for the tested genes, but
      did not form any biofilm. No significant differences were observed between
      biofilm formation and the presence of the esp, gelE and cyl genes in the
      pathogenic and fecal isolates (P >0.05). CONCLUSION: The presence of the esp,
      gelE and cyl genes might not be determining factors for biofilm formation in
      enterococci and other mechanisms might be involved in this process.

PMID- 29027385
TI  - Antimicrobial Susceptibilities of Enterobacteriaceae in Community-Acquired
      Urinary Tract Infections during a 5-year Period: A Single Hospital Study in
      Korea.
AB  - BACKGROUND: Through investigating antimicrobial susceptibility patterns of
      Enterobacteriaceae in community-acquired urinary tract infection (CA-UTI), we
      provide basic evidence for the use of empirical antibiotics in CA-UTI. MATERIALS
      AND METHODS: We retrospectively reviewed the medical records of patients over the
      age of 19 years who visited a hospital in Seoul between January 2012 and December
      2016 for a CA-UTI. Urine cultures were used to identify causative organisms. We
      investigated extended-spectrum beta-lactamase (ESBL) production and the
      antimicrobial susceptibility of Enterobactereiaceae. We evaluated recommended
      empirical antibiotics numerically by calculating the syndrome-specific likelihood
      of inadequate therapy (LIT) for the last 2 years (interpretation of the LIT A
      value: 1 out of A people is likely to receive inadequate empirical antibiotics).
      RESULTS: Urine cultures were performed in 1,605 out of 2,208 patients who were
      diagnosed with CA-UTI, and causative pathogens were identified in 1,134 (70.7%)
      cases. There were 998 (88.0%) cases of Enterobacteriaceae and Escherichia coli
      was the most common pathogen, accounting for 80.3% of cases (911 cases). The
      overall resistance rates to trimethoprim-sulfamethoxazole, fluoroquinolones, and
      cefotaxime were 31.7%, 23.2%, and 13.5%, respectively. There were 128 (10.8%)
      cases of ESBL-producing Entererobacteriaceae with an increasing but non
      significant trend (P = 0.255). The LIT for CA-UTI in the past two years was
      highest for ertapenem and imipenem. Fluoroquinolones ranked 11th, with a LIT of
      8.2, and cefotaxime ranked higher, at 10.5. In ESBL-producing Enterobacteriaceae,
      except for carbapenems, amikacin and piperacillin-tazobactam showed the highest
      susceptibility rates at 99.2% and 94.3%, respectively. CONCLUSION: Empiric
      treatment with fluoroquinolones in CA-UTI should be carefully considered, given
      the high resistance rate. The proportion of ESBL-producing Entererobacteriaceae
      in CA-UTI has increased to a high level in Korea. Amikacin and piperacillin
      tazobactam could be considered for empiric treatment in patients at risk for ESBL
      producing Entererobacteriaceae when considering alternatives to carbapenems.

PMID- 29027383
TI  - Immunological Prediction of Cytomegalovirus (CMV) Replication Risk in Solid Organ
      Transplantation Recipients: Approaches for Regulating the Targeted Anti-CMV
      Prevention Strategies.
AB  - The current cytomegalovirus (CMV) prevention strategies in solid organ
      transplantation (SOT) recipients have contributed towards overcoming the
      detrimental effects caused by CMV lytic infection, and improving the long-term
      success rate of graft survival. Although the quantification of CMV in peripheral
      blood is the standard method, and an excellent end-point for diagnosing CMV
      replication and modulating the anti-CMV prevention strategies in SOT recipients,
      a novel biomarker mimicking the CMV control mechanism is required. CMV-specific
      immune monitoring can be employed as a basic tool predicting CMV infection or
      disease after SOT, since uncontrolled CMV replication mostly originates from the
      impairment of immune responses against CMV under immunosuppressive conditions in
      SOT recipients. Several studies conducted during the past few decades have
      indicated the possibility of measuring the CMV-specific cell-mediated immune
      response in clinical situations. Among several analytical assays, the most
      advancing standardized tool is the QuantiFERON(r)-CMV assay. The T-Track(r) CMV
      kit that uses the standardized enzyme-linked immunospot assay is also widely
      employed. In addition to these assays, immunophenotyping and intracellular
      cytokine analysis using flow cytometry (with fluorescence-labeled monoclonal
      antibodies or peptide-major histocompatibility complex multimers) needs to be
      adequately standardized and validated for potential clinical applications.

PMID- 29027386
TI  - The Prevalence and Risk Factors of Renal Insufficiency among Korean HIV-Infected
      Patients: The Korea HIV/AIDS Cohort Study.
AB  - BACKGROUND: Renal disease is one of the leading causes of morbidity and mortality
      among people infected with human immunodeficiency virus (HIV). However, there are
      very few published studies about renal insufficiency in HIV-infected persons in
      Asia, especially in South Korea. MATERIALS AND METHODS: A cross-sectional study
      was performed to investigate the prevalence and risk factors of renal
      insufficiency, defined as <60 mL/min/1.73 m2, in subjects in the Korea HIV/AIDS
      Cohort Study enrolled from 19 institutions between December 2006 and July 2013.
      Data at entry into the cohort were analyzed. RESULTS: Of 454 enrolled subjects,
      24 (5.3%) showed renal insufficiency at entry into the cohort. The mean age of
      patients in the renal insufficiency group was 5.28 years and the majority were
      male subjects (91.7%). All the patients were receiving antiretroviral agents,
      mostly protease inhibitor-based regimens (76.4%), for an average of 19 months. In
      univariate analysis, older age (P = 0.002), diabetes mellitus (DM) (P = 0.0002),
      unknown route of transmission (P = 0.007), and taking indinavir (P = 0.0022) were
      associated with renal insufficiency. In multivariable analysis, older age [odds
      ratio (OR) 1.07, 95% confidence interval (CI) 1.03-1.12, P = 0.002], DM [OR 3.03,
      95% CI 1.17-7.82, P = 0.022], unknown route of transmission [OR 6.15, 95% CI 1.77
      21.33, P = 0.004], and taking indinavir [OR 3.07, 95% CI 1.17-8.05, P = 0.023]
      were independent risk factors of renal insufficiency. CONCLUSION: The prevalence
      of renal insufficiency in HIV-infected subjects in this study was relatively low,
      similar to that in other countries. Aging, DM, and taking indinavir were
      significantly associated with decreased glomerular filtration rate. Furthermore,
      unknown route of transmission was an independent risk factor, which was
      interpreted as a reflection of patient compliance. Further studies on the
      incidence and risk factors of renal insufficiency during HIV infection using
      follow-up cohort data are necessary.

PMID- 29027387
TI  - Safety and Efficacy of Ziagen (Abacavir Sulfate) in HIV-Infected Korean Patients.
AB  - BACKGROUND: Abacavir is a widely-used nucleoside reverse transcriptase inhibitor
      for the treatment of human immunodeficiency virus (HIV) infection. Mandatory
      postmarketing surveillance was conducted in Korea to monitor the safety and
      evaluate the effectiveness of Ziagen(r) (abacavir sulfate 300 mg; ViiV
      Healthcare, Middlesex, UK). MATERIALS AND METHODS: An open-label, multi-center,
      non-interventional postmarketing surveillance study was conducted from June 2010
      to June 2016 to monitor the safety and effectiveness of Ziagen across 12
      hospitals in Korea. Subjects older than 18 years taking Ziagen according to
      prescribing information were enrolled. The primary outcome was defined as the
      occurrence of any adverse events after Ziagen administration. Secondary outcomes
      included the occurrence of adverse drug reactions, occurrence of serious adverse
      events, and effectiveness of Ziagen administration. RESULTS: A total of 669
      patients were enrolled in this study, with a total observation period of 1047.8
      person-years. Of these, 90.7% of patients were male. The mean age of patients was
      45.8+/-11.9 years. One-hundred ninety-six (29.3%) patients reported 315 adverse
      events, and four patients reported seven serious adverse events, without any
      fatal events. There was one potential case of an abacavir hypersensitivity
      reaction. Among the 97 adverse drug reactions that were reported from 75
      patients, the most frequent adverse drug reactions included diarrhea (12 events),
      dyspepsia (10 events), and rash (9 events). No ischemic heart disease was
      observed. In the effectiveness analysis, 91% of patients achieved HIV-1 RNA under
      50 copies/mL after 24 months of observation with abacavir administration.
      CONCLUSION: Our data showed the safety and effectiveness of Ziagen in a real
      world setting. During the study period, Ziagen was well-tolerated, with one
      incident of a clinically suspected abacavir hypersensitivity reaction. The
      postmarketing surveillance of Ziagen did not highlight any new safety
      information. These data may be helpful in understanding abacavir and the HIV
      treatment practices in Korea.

PMID- 29027388
TI  - Causes of HIV Drug Non-Adherence in Korea: Korea HIV/AIDS Cohort Study, 2006
      2015.
AB  - We aimed to determine the initial adherence of HIV cohort patients to ART
      (antiretroviral therapy), and reasons for non-adherence. Patients who received
      ART at the time of enrollment in the Korea HIV/AIDS Cohort were included in this
      study. Treatment adherence was determined at the baseline interview by self
      reported questionnaire. Eight-hundred thirty two HIV-infected patients received
      ART. Of these, 253 (30.4%) patients skipped ART more than once a month. The most
      common reason of skipping medication was "simply forgot" (60.4%).

PMID- 29027390
TI  - Renal Disease in Persons Infected with Human Immunodeficiency Virus in Korea.

PMID- 29027389
TI  - Biofilm Formation and Antimicrobial Resistance in Enterococcus.

PMID- 29027391
TI  - Regional Experience of Abacavir: Valuable but Still has Unanswered Question.

PMID- 29027392
TI  - Summary of Guidelines for the Use of Pre-Exposure Prophylaxis for HIV in Korea.
AB  - There are several guidelines for the use of pre-exposure prophylaxis (PrEP) for
      human immunodeficiency virus (HIV) which are used in other countries. However,
      the implementation of such guidelines in each country should be modified
      according to the country's clinical and epidemiological situation. Therefore, The
      Korean Society for AIDS founded a committee in 2016 to develop guidelines for the
      use of PrEP for HIV that are optimal for Korea's clinical and epidemiological
      situation. These guidelines aim to provide comprehensive information for PrEP
      implementation in Korea. The recommendations contain important information for
      physicians working to prevent HIV infection in actual clinical fields. The
      committee will regularly review and revise the guidelines based on changes in
      PrEP administration and HIV prevention practices.

PMID- 29027393
TI  - Down-regulated serum microRNA-101 is associated with aggressive progression and
      poor prognosis of cervical cancer.
AB  - OBJECTIVE: MicroRNAs (miRNAs) play a vital role in pathogenesis and progression
      of many cancers, including cervical cancer. However, importance of serum level of
      miR-101 in cervical cancer has rarely been studied. In the present study,
      clinical significance and prognostic value of serum miR-101 for cervical cancer
      was investigated. METHODS: Association between miR-101 level in cervical cancer
      tissues and prognosis of patients was analyzed by using data retrieved from The
      Cancer Genome Atlas (TCGA) database, which was followed with our clinical study
      in which miR-101 serum level comparison between cervical cancer patients and
      healthy controls was conducted by real-time quantitative polymerase chain
      reaction (PCR). RESULTS: TCGA database demonstrated that miR-101 was down
      regulated in cervical cancer tissues compared with normal cervical tissues, and
      univariate Cox regression analysis indicated that decreased miR-101 expression
      was a highly significant negative risk factor. Similar trend was found in the
      serum miR-101. Serum level of miR-101 was associated with International
      Federation of Gynecology and Obstetrics (FIGO) stage (p=0.003), lymph node
      metastasis (p=0.001), and serum squamous cell carcinoma antigen (SCC-Ag) level >4
      (p=0.007). The overall survival time of cervical cancer patients with a higher
      level of serum miR-101 was significantly longer than that of patients with a
      lower level of serum miR-101. Moreover, multivariate Cox regression analysis
      indicated that the down-regulated serum level of miR-101 was an independent
      predictor for the unfavorable prognosis of cervical cancer. CONCLUSION: Serum
      level of miR-101 is closely associated with metastasis and prognosis of cervical
      cancer; and, hence could be a potential biomarker and prognostic predictor for
      cervical cancer.

PMID- 29027394
TI  - Assessing the effect of guideline introduction on clinical practice and outcome
      in patients with endometrial cancer in Japan: a project of the Japan Society of
      Gynecologic Oncology (JSGO) guideline evaluation committee.
AB  - OBJECTIVE: The Japan Society of Gynecologic Oncology (JSGO) published the first
      practice guideline for endometrial cancer in 2006. The JSGO guideline evaluation
      committee assessed the effect of this guideline introduction on clinical practice
      and patient outcome using data provided by the Japan Society of Obstetrics and
      Gynecology (JSOG) cancer registration system. METHODS: Data of patients with
      endometrial cancer registered between 2000 and 2012 were analyzed, and
      epidemiological and clinical trends were assessed. The influence of guideline
      introduction on survival was determined by analyzing data of patients registered
      between 2004 and 2009 using competing risk model. RESULTS: In total, 65,241 cases
      of endometrial cancer were registered. Total number of patients registered each
      year increased about 3 times in the analyzed period, and the proportion of older
      patients with type II endometrial cancer rapidly increased. The frequency of
      lymphadenectomy had decreased not only among the low-recurrence risk group but
      also among the intermediate- or high-recurrence risk group. Adjuvant therapy was
      integrated into chemotherapy (p<0.001). Overall survival did not significantly
      differ before and after the guideline introduction (hazard ratio [HR]=0.891;
      p=0.160). Additional analyses revealed patients receiving adjuvant chemotherapy
      showed better prognosis than those receiving adjuvant radiation therapy when
      limited to stage I or II (HR= 0.598; p=0.003). CONCLUSION: It was suggested that
      guideline introduction influenced the management of endometrial cancer at several
      aspects. Better organized information and continuous evaluation are necessary to
      understand the causal relationship between the guideline and patient outcome.

PMID- 29027395
TI  - Prognostic value of programmed death-ligand 1 (PD-L1) expression in ovarian clear
      cell carcinoma.
AB  - OBJECTIVE: Programmed death-ligand 1 (PD-L1) was expressed in various tumors and
      antibodies targeting its receptor programmed cell death-1 (PD-1) are emerging
      cancer therapeutics. This study was designed to evaluate the expression of PD-L1
      and its correlation with clinicopathologic features and clinical outcomes in
      ovarian clear cell carcinoma (OCCC). METHODS: The PD-L1 expression was measured
      by tissue-microarray-based immunohistochemistry from 122 eligible patients
      diagnosed with OCCC. The associations of clinicopathologic features with
      progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan
      Meier method and multivariate analysis was further performed by Cox regression
      model. RESULTS: Overall, high PD-L1 expression (PD-L1(high)) was observed in
      44.7% (55/123) of OCCC patients, and was strongly associated with advanced stages
      (p=0.020), positive ascitic fluid (p=0.016), platinum-resistant (PR) disease
      (p=0.045), and recurrence (p=0.038). Moreover, patients with PD-L1(high) were
      associated with poorer OS (hazard ratio [HR]=2.877; p=0.001) and PFS (HR=1.843;
      p=0.021) than those with low PD-L1 expression (PD-L1(low)). In subgroup analysis,
      PD-L1(high) patients experienced a poorer PFS (HR=1.926; p=0.044) and OS
      (HR=2.492; p=0.021) than PD-L1(low) cases among advanced stages (III-IV), but
      this difference was not observed in stage I-II patients. Meanwhile, PD-L1(high)
      was associated with poorer prognosis than PD-L1(low) in PR patients (OS,
      HR=2.253; p=0.037; PFS, HR=1.448; p=0.233). Multivariate analysis revealed that
      PD-L1(high) and advanced stages (III-IV) were adverse independent prognosticators
      for both PFS (HR(PD-L1)=2.0; p(PD-L1)=0.038; HR(stage)=10.2; p(stage)<0.001) and
      OS (HR(PD-L1)=3.0; p(PD-L1)=0.011; HR(stage)=14.3; p(stage)<0.001). CONCLUSION:
      PD-L1(high) might serve as a risk factor for PFS and OS in patients with OCCC. It
      is possible that immunotherapy targeting PD-L1 pathway could be used in OCCC.

PMID- 29027396
TI  - Comparison of three different risk-stratification models for predicting lymph
      node involvement in endometrioid endometrial cancer clinically confined to the
      uterus.
AB  - OBJECTIVE: To compare the clinical validity of the Gynecologic Oncology Group-99
      (GOG-99), the Mayo-modified and the European Society for Medical Oncology (ESMO)
      modified criteria for predicting lymph node (LN) involvement in women with
      endometrioid endometrial cancer (EC) clinically confined to the uterus. METHODS:
      A total of 625 consecutive women who underwent comprehensive surgical staging for
      endometrioid EC clinically confined to the uterus were divided into low- and high
      risk groups according to the GOG-99, the Mayo-modified, and the ESMO-modified
      criteria. Lymphovascular space invasion is the cornerstone of risk stratification
      according to the ESMO-modified criteria. These 3 risk stratification models were
      compared in terms of predicting LN positivity. RESULTS: Systematic LN dissection
      was achieved in all patients included in the study. LN involvement was detected
      in 70 (11.2%) patients. LN involvement was correctly estimated in 51 of 70 LN
      positive patients according to the GOG-99 criteria (positive likelihood ratio
      [LR+], 3.3; negative likelihood ratio [LR-], 0.4), 64 of 70 LN-positive patients
      according to the ESMO-modified criteria (LR+, 2.5; LR-, 0.13) and 69 of the 70 LN
      positive patients according to the Mayo-modified criteria (LR+, 2.2; LR-, 0.03).
      The area under curve of the Mayo-modified, the GOG-99 and the ESMO-modified
      criteria was 0.763, 0.753, and 0.780, respectively. CONCLUSION: The ESMO-modified
      classification seems to be the risk-stratification model that most accurately
      predicts LN involvement in endometrioid EC clinically confined to the uterus.
      However, the Mayo-modified classification may be an alternative model to achieve
      a precise balance between the desire to prevent over-treatment and the ability to
      diagnose LN involvement.

PMID- 29027397
TI  - Comparing treatment outcomes of stage IIIB cervical cancer patients between those
      with and without lower third of vaginal invasion.
AB  - OBJECTIVE: To evaluate treatment outcomes between stage IIIB cervical cancer with
      and without lower third of vaginal invasion (LTI) in terms of response to
      treatment and overall survival (OS). METHODS: Matching one patient with LTI for 2
      patients without LTI who had completed treatment between 1995 and 2012 were
      conducted by using treatment modalities (radiation therapy [RT] alone vs.
      concurrent chemoradiation therapy [CCRT]) and tumor histology (squamous cell
      carcinoma [SCC] vs. adenocarcinoma [ADC]). Treatment outcomes including complete
      response (CR) rate of RT/CCRT, patterns of treatment failure and survival
      outcomes were analyzed. RESULTS: Of 216 stage IIIB cervical cancer patients, 114
      of them had no LTI and 72 had LTI. Most of the patients (83.8%) had tumor
      histology as SCC. The CR rates between stage IIIB without LTI and with LTI were
      93.8% and 81.9% (p=0.009), and corresponding with disease progression at pelvis
      accounted for 18.2% and 34.4% (p=0.017), respectively. Distant metastasis was
      comparable between 2 groups of patients, 28.9% in patients without LTI and 29.5%
      in patients with LTI (p=0.988). The 2-year and 5-year OS of stage IIIB without
      LTI were 66.5% and 46.8% compared to stage IIIB with LTI which were 43.1% and
      28.9% (p=0.004), respectively. For multivariable analysis, stage IIIB with LTI
      was only the influential factor on OS with hazard ratio (HR) of 1.63 (p=0.012).
      CONCLUSION: Stage IIIB cervical cancer patients with LTI have poorer treatment
      outcomes including response to treatment and survival outcomes than patients in
      the same stage without LTI.

PMID- 29027398
TI  - Nutritional status, cachexia, and anorexia in women with peritoneal metastasis
      and intraperitoneal chemotherapy: a longitudinal analysis.
AB  - OBJECTIVE: To describe the nutritional status of women with peritoneal metastasis
      (PM) from recurrent ovarian, fallopian, or peritoneal cancer and to assess
      longitudinal variations of the cachexia-anorexia syndrome (CAS) during palliative
      pressurized intraperitoneal aerosol chemotherapy (PIPAC). METHODS: Nutritional
      assessment included body mass index (BMI), bioelectrical impedance analysis
      (BIA), and blood chemistry. CAS presence/absence was recorded before and during
      repeated cycles (1-11) of PIPAC. RESULTS: Eighty-four patients with peritoneal
      cancer (n=5) or PM from recurrent ovarian (n=77) or fallopian tube (n=2) cancer
      were included. At baseline, resting metabolism (RM) (1,432+/-172 kcal/day),
      visceral fat level (7.5+/-3.2), skeletal muscle mass (27.2%+/-4.6%), upper arm
      circumference (27.9+/-4.6 cm), lower leg circumference (35.1+/-3.9 cm), serum
      parameters (albumin [3.5+/-0.7 g/dL], total protein [6.3+/-0.9 g/dL], and
      transferrin [202+/-60 mg/dL]) were below normal limits. C-reactive protein (CRP)
      (4.3+/-6.8 mg/dL), caliper body fat (35.7%+/-6.3%), and total body fat mass
      (35.6%+/-8.5%) were above normal limits. Nineteen/84 (23%) patients had CAS at
      baseline. Deterioration or stabilization/improvement of CAS was observed in 9/55
      (16.4%) and 46/55 (83.6%) patients with follow-up data, respectively. Baseline
      body fat mass, visceral fat level, skeletal muscle mass, caliper body fat, BMI,
      ascites, Karnofsky index, RM, and CRP, as well as tumor response were not
      predictive of CAS deterioration. CONCLUSION: Nutritional decline and onset or
      deterioration of CAS are difficult to predict. Careful measuring and monitoring
      of nutritional parameters and CAS in all patients seems to be necessary in order
      to identify those patients in need of enteral/parenteral nutrition support.

PMID- 29027399
TI  - Early-stage node negative cervical adenocarcinoma and squamous cell carcinoma
      show similar survival outcomes after hysterectomy: a population-based study.
AB  - OBJECTIVE: To investigate the clinicopathological features and outcomes between
      node-negative, early-stage cervical squamous cell carcinoma (SCC) and
      adenocarcinoma (AC) after hysterectomy. METHODS: Patients diagnosed with
      International Federation of Gynecology and Obstetrics (FIGO) stages I-IIA
      cervical SCC and AC between 1988 and 2013 were retrospectively reviewed using the
      Surveillance, Epidemiology, and End Results database. We used propensity score
      matching to balance patient baseline characteristics. Univariate and multivariate
      Cox regression analyses were used for prognostic analyses of cause-specific
      survival (CSS) and overall survival (OS). RESULTS: A total of 9,858 patients were
      identified, comprising 6,117 patients (62.1%) and 3,741 (37.9%) patients with
      cervical SCC and AC, respectively. Compared with cervical SCC, cervical AC cases
      were more likely to be younger, diagnosed after 2000, white, and have well
      differentiated and FIGO stage IB1 disease. For SCC and AC, the 10-year CSS rates
      were 93.4% and 94.7%, respectively (p=0.011), and the 10-year OS rates were 89.6%
      and 92.2%, respectively (p<0.001). Multivariate analysis revealed that age,
      ethnicity, tumor grade, and FIGO stage were independent prognostic factors of CSS
      and OS, but that histologic subtype was not associated with CSS and OS. In the
      propensity score-matched patient population, univariate and multivariate analyses
      also showed that histologic subtype was not associated with survival outcomes.
      CONCLUSION: Cervical AC has equivalent survival to cervical SCC in node-negative,
      early-stage disease after hysterectomy and lymphadenectomy.

PMID- 29027400
TI  - Surgical and oncologic outcomes after robotic radical hysterectomy as compared to
      open radical hysterectomy in the treatment of early cervical cancer.
AB  - OBJECTIVE: The use of robotic radical hysterectomy has greatly increased in the
      treatment of early stage cervical cancer. We sought to compare surgical and
      oncologic outcomes of women undergoing robotic radical hysterectomy compared to
      open radical hysterectomy. METHODS: The clinic-pathologic, treatment, and
      recurrence data were abstracted through an Institutional Review Board-approved
      protocol at 2 separate large tertiary care centers in Seattle, Swedish Medical
      Center and the University of Washington. Data were collected from 2001-2012.
      Comparisons between the robotic and open cohorts were made for complications,
      recurrence, progression-free survival (PFS), and overall survival (OS). RESULTS:
      In the study period, 109 robotic radical hysterectomies were performed. These
      were compared to 202 open radical hysterectomies. The groups were comparable in
      terms of age and body mass index (BMI). Length of stay (LOS) was considerably
      shorter in the robotic group (42.7 vs. 112.6 hours, p<0.001) as was estimated
      blood loss (EBL; 105.9 vs. 482.6 mL, p<0.001). There were more complications in
      the open radical hysterectomy group, 23.4% vs. 9.2% in the robotic group
      (p=0.002). The recurrence rate was comparable between the groups (10.1% vs.
      10.4%, p=0.730). In multivariate adjusted analysis, robotic surgery was not a
      statistically significant predictor of PFS (p=0.230) or OS (0.85). CONCLUSION:
      Our study, one of the largest multi-institution cohorts of patients undergoing
      robotic radical hysterectomy, suggest robotic radical hysterectomy leads to
      comparable oncologic outcomes in the treatment of early stage cervical cancer
      with improved short-term surgical outcomes such as decreased LOS and EBL.

PMID- 29027402
TI  - Impact of vaginal cylinder diameter on outcomes following brachytherapy for early
      stage endometrial cancer.
AB  - OBJECTIVE: To examine the outcomes (tolerability, toxicity, and recurrence) of
      vaginal brachytherapy (VBT) among endometrial cancer (EC) patients treated with
      small cylinder size. METHODS: Patients with EC who received adjuvant VBT between
      September 2011 and December 2015 were reviewed. Patients were fitted with the
      largest vaginal cylinder they could comfortably accommodate, from 2.0-3.0 cm
      diameter. Small cylinders were defined as size 2.3 cm or less. Patient, tumor, or
      treatment characteristics were correlated with need for small cylinders.
      Treatment tolerability, measures of gastrointestinal (GI), genitourinary (GU),
      and vaginal toxicity, and rates of recurrence were analyzed. RESULTS: Three
      hundred four patients were included. Small cylinders were used in 51 patients
      (17%). Normal body mass index (BMI; p<0.001), nulligravidity (p<0.001), and
      shorter vaginal length (p<0.001) were associated with small cylinder size. There
      was no acute or late grade 3 toxicity. Rates of acute (grade 1-2) GI, GU, or
      vaginal symptoms were low (10%, 11%, and 19%, respectively). Small cylinder size
      was associated with increased likelihood of reporting acute GI (p<0.05) but not
      GU or vaginal symptoms. Small cylinder size was associated with higher risk of
      grade 1-2 vaginal stenosis (odds ratio [OR]=4.7; 95% confidence interval [CI]=1.5
      14.7; p=0.007). There was no association between cylinder size and recurrence
      rate (p=0.55). CONCLUSION: VBT is generally very well tolerated, however,
      patients fitted with smaller cylinders (commonly nulligravid and low BMI) may
      have increased side effects. Further study to improve the dosimetry of VBT for
      patients requiring small cylinders may be worthwhile.

PMID- 29027401
TI  - Identification of DNA methylation associated gene signatures in endometrial
      cancer via integrated analysis of DNA methylation and gene expression
      systematically.
AB  - OBJECTIVE: Endometrial cancer (EC) is a common gynecologic cancer worldwide.
      However, the pathogenesis of EC has not been epigenetically elucidated. Here,
      this study aims to describe the DNA methylation profile and identify favorable
      gene signatures highly associated with aberrant DNA methylation changes in EC.
      METHODS: The data regarding DNA methylation and gene expression were downloaded
      from The Cancer Genome Atlas (TCGA) database. Differentially methylated CpG sites
      (DMCs), differentially methylated regions (DMRs), and differentially expressed
      genes (DEGs) were identified, and the relationship between the 2 omics was
      further analyzed. In addition, weighted CpG site co-methylation network (WCCN)
      was constructed followed by an integrated analysis of DNA methylation and gene
      expression data. RESULTS: Four hundred thirty-one tumor tissues and 46 tissues
      adjacent tumor of EC patients were analyzed. One thousand one hundred thirty-five
      DMCs (merging to 10 DMRs), and 1,488 DEGs were obtained between tumor and normal
      groups, respectively. One hundred forty-eight DMCs-DEGs correlated pairs and 13
      regional DMCs-DEGs pairs were obtained. Interestingly, we found that some hub
      genes in 2 modules among 8 modules of WCCN analysis were down-regulated in tumor
      samples. Furthermore, protocadherins (PCDHs) clusters, DDP6, TNXB, and ZNF154
      were identified as novel deregulated genes with altered methylation in EC.
      CONCLUSION: Based on the analysis of DNA methylation in a systematic view, the
      potential long-range epigenetic silencing (LRES) composed of PCDHs was reported
      in ECs for the first time. PCDHs clusters, DDP6, and TNXB were firstly found to
      be associated with tumorigenesis, and may be novel candidate biomarkers for EC.

PMID- 29027403
TI  - Survival of gynecological cancers in Turkey: where are we at?
AB  - OBJECTIVE: To investigate the 5-year relative survival rates in gynecological
      cancers diagnosed and treated in Turkey by year 2009 and to compare the results
      with developed countries. METHODS: Data of patients diagnosed for ovarian, corpus
      uteri or cervix uteri cancer at year 2009 are collected from 9 national cancer
      registry centers. Date of deaths are retracted from governmental Identity
      Information Sharing System (KPS). In order to calculate relative survival rates,
      national general population mortality tables are obtained from Turkish
      Statistical Institute (TurkStat). Hakulinen method is used for computing curves
      by R program. Data for European, Asian and some developed countries were obtained
      from official web pages. RESULTS: A total of 1,553 patients are evaluated. Among
      these, 713 (45.9%) are corpus uteri cancers, while remaining 489 (31.5%) are
      ovarian and 351 (22.6%) are cervix uteri. Five-year overall relative survival
      rates are 85%, 50%, and 62% for corpus uteri, ovarian, and cervix uteri,
      respectively. These figures are between 73%-87% for corpus uteri, 31%-62% for
      ovarian and 61%-80% for cervix uteri in developed countries. Stage is the most
      important factor for survival in all cancers. Five-year relative survival rates
      in corpus uteri cancers are 92%, 66%, and 38% for localized, regional, and
      distant metastatic disease, respectively. These figures are 77%, 57%, and 29% for
      ovarian; 80%, 50%, and 22% for cervix uteri. CONCLUSION: This is the first report
      from Turkey giving national overall relative survival for gynecological cancers
      from a population based cancer registry system.

PMID- 29027404
TI  - Transvaginal ultrasound versus magnetic resonance imaging for preoperative
      assessment of myometrial infiltration in patients with endometrial cancer: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To compare the diagnostic accuracy of transvaginal ultrasound (TVS)
      and magnetic resonance imaging (MRI) for detecting myometrial infiltration (MI)
      in endometrial carcinoma. METHODS: An extensive search of papers comparing TVS
      and MRI in assessing MI in endometrial cancer was performed in MEDLINE (PubMed),
      Web of Science, and Cochrane Database from January 1989 to January 2017. Quality
      was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2)
      tool. RESULTS: Our extended search identified 747 citations but after exclusions
      we finally included in the meta-analysis 8 articles. The risk of bias for most
      studies was low for most 4 domains assessed in QUADAS-2. Overall, pooled
      estimated sensitivity and specificity for diagnosing deep MI were 75% (95%
      confidence interval [CI]=67%-82%) and 82% (95% CI=75%-93%) for TVS, and 83% (95%
      CI=76%-89%) and 82% (95% CI=72%-89%) for MRI, respectively. No statistical
      differences were found when comparing both methods (p=0.314). Heterogeneity was
      low for sensitivity and high for specificity for TVS and MRI. CONCLUSION: MRI
      showed a better sensitivity than TVS for detecting deep MI in women with
      endometrial cancer. However, the difference observed was not statistically
      significant.

PMID- 29027405
TI  - Safety of fertility-sparing surgery for stage I ovarian clear cell carcinoma.

PMID- 29027406
TI  - Comparing prediction models for lymph node metastasis risk in endometrial cancer:
      the winner may not take it all.

PMID- 29027407
TI  - Challenges in translation: models to promote translation.
AB  - We first discuss the main obstacles for clinical translation of biophotonics
      technologies, in particular, the different valleys of death, after which we
      present different examples of ways to bridge these gaps, remove the obstacles,
      and promote clinical translation.

PMID- 29027408
TI  - Dual-modal cancer detection based on optical pH sensing and Raman spectroscopy.
AB  - A dual-modal approach using Raman spectroscopy and optical pH sensing was
      investigated to discriminate between normal and cancerous tissues. Raman
      spectroscopy has demonstrated the potential for in vivo cancer detection.
      However, Raman spectroscopy has suffered from strong fluorescence background of
      biological samples and subtle spectral differences between normal and disease
      tissues. To overcome those issues, pH sensing is adopted to Raman spectroscopy as
      a dual-modal approach. Based on the fact that the pH level in cancerous tissues
      is lower than that in normal tissues due to insufficient vasculature formation,
      the dual-modal approach combining the chemical information of Raman spectrum and
      the metabolic information of pH level can improve the specificity of cancer
      diagnosis. From human breast tissue samples, Raman spectra and pH levels are
      measured using fiber-optic-based Raman and pH probes, respectively. The pH
      sensing is based on the dependence of pH level on optical transmission spectrum.
      Multivariate statistical analysis is performed to evaluate the classification
      capability of the dual-modal method. The analytical results show that the dual
      modal method based on Raman spectroscopy and optical pH sensing can improve the
      performance of cancer classification.

PMID- 29027409
TI  - [Developing traditional Chinese medicine injection is the need for curing
      sickness to save patients].
AB  - Safety issues of traditional Chinese medicine injections has been heated debate.
      There are two diametrically opposed views: it should be used reasonable and
      developed healthily or be forbidden to use. Some people have many
      misunderstandings and prejudices about the safety of traditional Chinese medicine
      injections. Compared with western medicine,traditional Chinese medicine has its
      own particularity. Traditional Chinese medicine has complex components. Its
      research and clinical application is different from western medicine. Adverse
      reactions of traditional Chinese medicine injections are related to many
      factors,such as a large number of irrational use,blind use of traditional Chinese
      medicine injections and western medicine injections,counterfeit and substandard
      drugs,incorrect methods of intravenous infusion,toxicity of supplementary
      materials,drug ingredients. Developing traditional Chinese medicine injection is
      the need for curing sickness to save patients. The purposeful, targeted,
      organized and planned systematic research of traditional Chinese medicine
      injections should be strengthened,especially the safety of traditional Chinese
      medicine. Strengthen supervision and control of rational drug use.Strengthen the
      examination and approval,supervision and management of all aspects to ensure the
      safety of patients.

PMID- 29027410
TI  - [Quality by design approaches for pharmaceutical development and manufacturing of
      Chinese medicine].
AB  - The pharmaceutical quality was built by design, formed in the manufacturing
      process and improved during the product's lifecycle. Based on the comprehensive
      literature review of pharmaceutical quality by design (QbD), the essential ideas
      and implementation strategies of pharmaceutical QbD were interpreted. Considering
      the complex nature of Chinese medicine, the "4H" model was innovated and proposed
      for implementing QbD in pharmaceutical development and industrial manufacture of
      Chinese medicine product. "4H" corresponds to the acronym of holistic design,
      holistic information analysis, holistic quality control, and holistic process
      optimization, which is consistent with the holistic concept of Chinese medicine
      theory. The holistic design aims at constructing both the quality problem space
      from the patient requirement and the quality solution space from
      multidisciplinary knowledge. Holistic information analysis emphasizes
      understanding the quality pattern of Chinese medicine by integrating and mining
      multisource data and information at a relatively high level. The batch-to-batch
      quality consistence and manufacturing system reliability can be realized by
      comprehensive application of inspective quality control, statistical quality
      control, predictive quality control and intelligent quality control strategies.
      Holistic process optimization is to improve the product quality and process
      capability during the product lifecycle management. The implementation of QbD is
      useful to eliminate the ecosystem contradictions lying in the pharmaceutical
      development and manufacturing process of Chinese medicine product, and helps
      guarantee the cost effectiveness.

PMID- 29027411
TI  - [Analysis and countermeasure for quality risk in process of traditional Chinese
      medicine preparations].
AB  - Product quality relies on not only testing methods,but also the design and
      development, production control and product manufacturing all aspects of
      logistics management. Quality comes from the process control level.Therefore, it
      is very important to accurately identify the factors that may induce quality risk
      in the production process and quality control measures correspondingly.This
      article systematically analyzes the source of the quality risk of all aspects of
      the production process in traditional Chinese medicine preparation. Discussing
      ways and methods of quality risk identification of traditional Chinese medicine
      preparation and providing references for perfecting the whole process quality
      management of traditional Chinese medicine preparation.

PMID- 29027412
TI  - [Research advances in secondary development of Chinese patent medicines based on
      quality by design concept].
AB  - Quality by design (QbD) concept is an advanced pharmaceutical quality control
      concept. The application of QbD concept in the research and development of
      pharmaceutical processes of traditional Chinese medicines (TCM) mainly contains
      five parts, including the definition of critical processes and their evaluation
      criteria, the determination of critical process parameters and critical material
      attributes, the establishment of quantitative models, the development of design
      space, as well as the application and continuous improvement of control strategy.
      In this work, recent research advances in QbD concept implementation methods in
      the secondary development of Chinese patent medicines were reviewed, and five
      promising fields of the implementation of QbD concept were pointed out, including
      the research and development of TCM new drugs and Chinese medicine granules for
      formulation, modeling of pharmaceutical processes, development of control
      strategy based on industrial big data, strengthening the research of process
      amplification rules, and the development of new pharmaceutical equipment.?.

PMID- 29027413
TI  - [Application of quality by design in granulation process for ginkgo leaf tablet
      (I): comprehensive characterization of granule properties].
AB  - In this paper, the granules intermediate prepared from the wet granulation
      process of ginkgo leaf tablet were taken as the research object, and then the
      stackability, homogeneity, flowability, compressibility and stability of granules
      were characterized by using micromeritics evaluation method. The physical
      fingerprint of granules were constructed by 16 indexes including bulk density,
      tapped density, span, width, relative homogeneity index, aspect ratio, Hausner
      ratio, angle of repose, granule flow time, inter-particle porosity, Carr index,
      specific surface area, pore volume, pore size distribution, loss on drying and
      hygroscopicity. Furthermore, compressibility parameters (i.e. index of parameter,
      index of parametric profile and index of good compression) were employed to
      analyze the compressibility characteristics of the granules. Two principal
      components (first principal component representing dimension parameter and second
      principal component representing morphology parameter), could be extracted from
      the physical fingerprint by the principal component analysis (PCA). The granules'
      physical fingerprint is of great importance to evaluate the batch-to-batch
      quality consistency of Ginkgo biloba granules and analyze the potential impacts
      of granules' quality attributes on product quality, which can provide guidance
      for the granules' quality control and process development.?.

PMID- 29027414
TI  - [Application of quality by design in granulation process for ginkgo leaf tablet
      (II): identification of critical quality attributes].
AB  - Quality by design (QbD) highlights the concept of "begin with the end", which
      means to thoroughly understand the target product quality first, and then guide
      pharmaceutical process development and quality control throughout the whole
      manufacturing process. In this paper, the Ginkgo biloba granules intermediates
      were taken as the research object, and the requirements of the tensile strength
      of tablets were treated as the goals to establish the methods for identification
      of granules' critical quality attributes (CQAs) and establishment of CQAs'
      limits. Firstly, the orthogonal partial least square (OPLS) model was adopted to
      build the relationship between the micromeritic properties of 29 batches of
      granules and the tensile strength of ginkgo leaf tablets, and thereby the
      potential critical quality attributes (pCQAs) were screened by variable
      importance in the projection (VIP) indexes. Then, a series of OPLS models were
      rebuilt by reducing pCQAs variables one by one in view of the rule of VIP values
      from low to high in sequence. The model performance results demonstrated that
      calibration and predictive performance of the model had no decreasing trend after
      variables reduction. In consideration of the results from variables selection as
      well as the collinearity test and testability of the pCQAs, the median particle
      size (D50) and the bulk density (Da) were identified as critical quality
      attributes (CQAs). The design space of CQAs was developed based on a multiple
      linear regression model established between the CQAs (D50 and Da) and the tensile
      strength. The control constraints of the CQAs were determined as 170 MUm< D50<500
      MUm and 0.30 g*cm-3<Da<0.44 g*cm-3 according to the design space, which provided
      a basis for controlling and optimizing the wet granulation process of the ginkgo
      leaf tablet.?.

PMID- 29027415
TI  - [Application of quality by design in granulation process for Ginkgo leaf tablet
      (III): process control strategy based on design space].
AB  - In this paper, under the guidance of quality by design (QbD) concept, the control
      strategy of the high shear wet granulation process of the ginkgo leaf tablet
      based on the design space was established to improve the process controllability
      and product quality consistency. The median granule size (D50) and bulk density
      (Da) of granules were identified as critical quality attributes (CQAs) and
      potential critical process parameters (pCPPs) were determined by the failure
      modes and effect analysis (FMEA). The Plackeet-Burmann experimental design was
      used to screen pCPPs and the results demonstrated that the binder amount, the wet
      massing time and the wet mixing impeller speed were critical process parameters
      (CPPs). The design space of the high shear wet granulation process was developed
      within pCPPs range based on the Box-Behnken design and quadratic polynomial
      regression models. ANOVA analysis showed that the P-values of model were less
      than 0.05 and the values of lack of fit test were more than 0.1, indicating that
      the relationship between CQAs and CPPs could be well described by the
      mathematical models. D50 could be controlled within 170 to 500 MUm, and the bulk
      density could be controlled within 0.30 to 0.44 g*cm-3 by using any CPPs
      combination within the scope of design space. Besides, granules produced by
      process parameters within the design space region could also meet the requirement
      of tensile strength of the ginkgo leaf tablet.?.

PMID- 29027416
TI  - [Application of quality by design in granulation process for ginkgo leaf tablet
      (IV): influence and control of raw materials' quality variation].
AB  - Raw materials' quality variation could affect the quality consistency of product
      and the clinical efficacy. In this paper, the high shear wet granulation (HSWG)
      process of the ginkgo leaf tablet was taken as the research object. Ginkgo biloba
      extracts and excipients microcrystalline cellulose collected from various sources
      and batches were used to simulate raw materials' quality variation. Real-time
      torque was recorded to analyze the viscosity of the wetting mass, and then by
      combining with physical fingerprint, the impact of physical quality variation of
      powders on granule properties could be investigated. Based on regime map thesis,
      whether the granules' nucleation mode was in mechanical dispersion regime was
      determined by calculating dimensionless parameters, which would lead to the
      unstable output in considerations of granule yield ratio and particle size
      distribution (PSD) curve. The orthogonal partial least square (OPLS) model was
      adopted to build the relationship between the micromeritic properties and the
      mediangranule size (D50) of Ginkgo biloba granules and then the critical material
      attributes (CMAs) were screened by variable importance in the projection (VIP)
      indexes. The results demonstrated that the properties of powders including
      hygroscopicity, angle of repose, Hausner ratio, Carr index, D10 and loss on
      drying affected the granule size. Besides, Ginkgo biloba granules were compressed
      into tablets. In view of tensile strength analysis, the raw materials' quality
      variation did not result in decrease of tensile strength of the ginkgo leaf
      tablets. The design space of critical quality attributes (CQAs) and the process
      design space which could cope with raw materials' quality variation were proved
      to be robust.?.

PMID- 29027417
TI  - [Primary exploration of key influential factors recognization method of Tanreqing
      injection].
AB  - To recognize the key influential factors during the liquid preparation process of
      Tanreqing injection, the near infrared(NIR) spectra of the raw materials and the
      operating parameters of 24 batches of physical manufacturing were recorded as
      independent variables, and the total soluble solids contents and the light
      inspection acceptance rate of the final products were collected as dependent
      variables. The calibration models were developed using the partial least-square
      regression (PLSR) method, and the correlation coefficients between the
      independent variables and the dependent variables were calculated. For the
      quantitative models, the correlation coefficients for the calibration and inner
      cross validation of total soluble solids contents and the light inspection
      acceptance rate reached 0.911 9, 0.724 2 and 0.873 8, 0.795 9, respectively.
      Using the correlation coefficients diagrams, several key influence factors were
      preliminarily determined, and the physical significance were analyzed combined
      with production experience. This work demonstrated that NIR spectroscopy with
      PLSR algorithm could be used for the key influential factors recognization during
      the liquid preparation process of Tanreqing injection and can be popularized to
      solve similar problems.?.

PMID- 29027418
TI  - [Optimization of ethanol reflux extraction process of red ginseng using a design
      space approach based on hazard and operability analysis].
AB  - Quality by design principle was used as a guideline in this study to optimize
      ethanol reflux extraction of red ginseng. Firstly, hazard and operability
      analysis(HAZOP) was used as a risk assessment tool to evaluate the hazard degree
      of process parameters.Ethanol concentration, the ratio of alcohol and herbal
      material (A/M ratio), and extraction time were identified as the critical process
      parameters(CPPs) according to HAZOP method.Secondly, Box-Behnken experimental
      design was applied to establish theregression models between CPPs and the process
      indices. Finally, the design space was calculated. The recommended operation
      space of parametersis as follows:alcohol concentration of 90.3%-90.7%, A/M ratio
      of 2.5-3.1 mL*g -1 and extraction time of 124-130 min. The study shows that the
      design space approach combined with the risk assessment using HAZOP has the
      potential to reduce the risk of red ginseng extraction process, which might
      ultimately improve the process control.?.

PMID- 29027419
TI  - [Optimization of lime milk precipitation process of Lonicera Japonica aqueous
      extract based on quality by design concept].
AB  - Design space approach was applied in this study to optimize the lime milk
      precipitation process of Lonicera Japonica (Jinyinhua) aqueous extract. The
      evaluation indices for this process were total organic acid purity and amounts of
      6 organic acids obtained from per unit mass of medicinal materials. Four critical
      process parameters (CPPs) including drop speed of lime milk, pH value after
      adding lime milk, settling time and settling temperature were identified by using
      the weighted standardized partial regression coefficient method. Quantitative
      models between process evaluation indices and CPPs were established by a stepwise
      regression analysis. A design space was calculated by a Monte-Carlo simulation
      method, and then verified. The verification test results showed that the
      operation within the design space can guarantee the stability of the lime milk
      precipitation process. The recommended normal operation space is as follows: drop
      speed of lime milk of 1.00-1.25 mL*min-1, pH value of 11.5-11.7, settling time of
      1.0-1.2 h, and settling temperature of 10-20 C.?.

PMID- 29027420
TI  - [Research on whole blending end-point evaluation method of Angong Niuhuang Wan
      based on QbD concept].
AB  - The blending end-point determination of Angong Niuhuang Wan (AGNH) is a key
      technology problem. The control strategy based on quality by design (QbD) concept
      proposes a whole blending end-point determination method, and provides a
      methodology for blending the Chinese materia medica containing mineral
      substances. Based on QbD concept, the laser induced breakdown spectroscopy (LIBS)
      was used to assess the cinnabar, realgar and pearl powder blending of AGNH in a
      pilot-scale experiment, especially the whole blending end-point in this study.
      The blending variability of three mineral medicines including cinnabar, realgar
      and pearl powder, was measured by moving window relative standard deviation
      (MWRSD) based on LIBS. The time profiles of realgar and pearl powder did not
      produce consistent results completely, but all of them reached even blending at
      the last blending stage, so that the whole proposal blending end point was
      determined. LIBS is a promising Process Analytical Technology (PAT) for process
      control. Unlike other elemental determination technologies such ICP-OES, LIBS
      does not need an elaborate digestion procedure, which is a promising and rapid
      technique to understand the blending process of Chinese materia medica (CMM)
      containing cinnabar, realgar and other mineral traditional Chinese medicine. This
      study proposed a novel method for the research of large varieties of traditional
      Chinese medicines.?.

PMID- 29027421
TI  - [Online endpoint detection algorithm for blending process of Chinese materia
      medica].
AB  - Blending process, which is an essential part of the pharmaceutical preparation,
      has a direct influence on the homogeneity and stability of solid dosage forms.
      With the official release of Guidance for Industry PAT, online process analysis
      techniques have been more and more reported in the applications in blending
      process, but the research on endpoint detection algorithm is still in the initial
      stage. By progressively increasing the window size of moving block standard
      deviation (MBSD), a novel endpoint detection algorithm was proposed to extend the
      plain MBSD from off-line scenario to online scenario and used to determine the
      endpoint in the blending process of Chinese medicine dispensing granules. By
      online learning of window size tuning, the status changes of the materials in
      blending process were reflected in the calculation of standard deviation in a
      real-time manner. The proposed method was separately tested in the blending
      processes of dextrin and three other extracts of traditional Chinese medicine.
      All of the results have shown that as compared with traditional MBSD method, the
      window size changes according to the proposed MBSD method (progressively
      increasing the window size) could more clearly reflect the status changes of the
      materials in blending process, so it is suitable for online application.

PMID- 29027422
TI  - [Continual improvement of quantitative analytical method development of Panax
      notogineng saponins based on quality by design].
AB  - This study is aimed to propose a continual improvement strategy based on quality
      by design (QbD). An ultra high performance liquid chromatography (UPLC) method
      was developed to accomplish the method transformation from HPLC to UPLC of Panax
      notogineng saponins (PNS) and achieve the continual improvement of PNS based on
      QbD, for example. Plackett-Burman screening design and Box-Behnken optimization
      design were employed to further understand the relationship between the critical
      method parameters (CMPs) and critical method attributes (CMAs). And then the
      Bayesian design space was built. The separation degree of the critical peaks
      (ginsenoside Rg1 and ginsenoside Re) was over 2.0 and the analysis time was less
      than 17 min by a method chosen from the design space with 20% of the initial
      concentration of the acetonitrile, 10 min of the isocratic time and 6%*min-1 of
      the gradient slope. At last, the optimum method was validated by accuracy
      profile. Based on the same analytical target profile (ATP), the comparison of
      HPLC and UPLC including chromatograph method, CMA identification, CMP-CMA model
      and system suitability test (SST) indicated that the UPLC method could shorten
      the analysis time, improve the critical separation and satisfy the requirement of
      the SST. In all, HPLC method could be replaced by UPLC for the quantity analysis
      of PNS.

PMID- 29027423
TI  - [Research progress of relationship between continuous cropping obstacles and
      microRNAs in Rehmannia glutinosa].
AB  - The efficacy of Rehmannia glutinosa which as a large quantity of traditional
      Chinese medicine is significant. However, the land must be given up after one
      season of R. glutinosa cultivation or replanted after a period of 8-10 years
      because of the severe continuous cropping obstacles. MicroRNAs is a class of
      endogenous non-coding small RNAs, which participate in regulation of
      physiological activities by target mRNA cleavage or translational repression in
      plants. In recent years,studies on the role of miRNAs in plants have made
      significant progresses,especially in medicinal plants.MiRNAs from some different
      medicinal plant species have been identified with regulatory effects.When plants
      are exposed to environmental stress, miRNAs act on stress-related genes and
      initiate stress-resistance mechanisms in the body against adverse factors. R.
      glutinosa is also a kind of environmental stress. It is conducive to deciphering
      the molecular mechanism of continuous cropping obstacles for us by researching
      miRNAs. This article reviews the production of miRNAs, mechanism, research
      approaches and characteristics of resisting the environmental stresses in plants,
      the development trends and future prospect of R. glutinosa miRNAs research.

PMID- 29027424
TI  - [Research progress on therapeutic targets of active components in Chinese herbs
      for treatment of nonalcoholic fatty liver disease].
AB  - Nonalcoholic fatty liver disease(NAFLD) is a kind of metabolic liver injury,
      which is closely associated with insulin resistance and genetic susceptibility.
      Traditional Chinese herbs used in the treatment of nonalcoholic fatty liver
      disease are widely investigated in recent years. A series of recent studies show
      that the effects of the active components in traditional Chinese herbs on NAFLD
      are associated with activating AMPK signaling pathway, improving insulin
      resistance, modulating the activity and expression of peroxisome proliferator
      activated receptor gamma, antioxidant and anti-inflammatory activities and
      regulating intestinal flora. In this review, the potential therapeutic targets of
      the active components from traditional Chinese herbs for NAFLD would be
      summarized to provide a new thought for further research and clinical treatment
      of nonalcoholic fatty liver disease.

PMID- 29027425
TI  - [Morphological characteristics of Chinese Perilla fruits].
AB  - The morphological traits of 55 Chinese Perilla fruit samples (size, 100 grains
      weight, color, hardness, surface ridge height) are described and the
      statistically analyzed. It can be divided into 6 categories by cluster analysis,
      namely: I, big grain (diameter 1.5 mm above and 100 grains weight above 0.16 g),
      low ridge, hard; II, big grain, low ridge, soft; III, big grain, high ridge,
      soft, fruit; IV, big grain. high ridge, gray brown or dark brown; V, small grain
      (diameter 1.5 mm below and 100 grain weight 0.16 g below), low ridge, hard, dark
      brown; VI, small grain, low ridge, hard, yellow brown. The 38 fruit samples were
      planted, among which 31 ones were P. frutescens var. frutescens, 4 ones P.
      frutescens var. crispa and 3 ones P. frutescens var. acuta. By chemotype
      classification, they were 29 PK type, 3 PA type, 2 PL type, 2 PP type, 1 EK type
      and 1 PAPK type. According the description of herb Perillae Fructus in China
      Pharmacopoeia, the plant originates from P. frutescens var. frutescens. In
      contrast, not all fruits of P. frutescens var. frutescens have accord features.
      The fruits with white pericarp are mainly from P. frutescens var. frutescens with
      purple leaves. The materials with small grain, low ridge, hard, yellow brown or
      dark brown, are likely to be PA type and mainly P. frutescens var. crispa.

PMID- 29027426
TI  - [Projection of potential geographic distribution of Apocynum venetum under
      climate change in northern China].
AB  - Apocynum venetum belongs to apocynaceae and is a perennial medicinal plant, its
      stem is an important textile raw materials. The projection of potential
      geographic distribution of A. venetum has an important significance for the
      protection and sustainable utilization of the plant. This study was conducted to
      determine the potential geographic distribution of A. venetum and to project how
      climate change would affect its geographic distribution. The projection
      geographic distribution of A. venetum under current bioclimatic conditions in
      northern China was simulated using MaxEnt software based on species presence data
      at 44 locations and 19 bioclimatic parameters. The future distributions of A.
      venetum were also projected in 2050 and 2070 under the climate change scenarios
      of RCP2.6 and RCP8.5 described in 5th Assessment Report of the Intergovernmental
      Panel on Climate Change (IPCC). The result showed that min air temperature of the
      coldest month, annual mean air temperature, precipitation of the coldest quarter
      and mean air temperature of the wettest quarter dominated the geographic
      distribution of A. venetum. Under current climate, the suitable habitats of A.
      venetum is 11.94% in China, the suitable habitats are mainly located in the
      middle of Xinjiang, in the northern part of Gansu, in the southern part of
      Neimeng, in the northern part of Ningxia, in the middle and northern part of
      Shaanxi, in the southern part of Shanxi, in the middle and northern part of
      Henan, in the middle and southern part of Hebei, Shandong, Tianjin, in the
      southern part of Liaoning and part of Beijing. From 2050 to 2070, the model
      outputs indicated that the suitable habitats of A. venetum would decrease under
      the climate change scenarios of RCP2.6 and RCP8.5.

PMID- 29027428
TI  - [Gene cloning and expression analysis of benzoic acid stress responsive
      transcription factor WRKY7 in Panax ginseng].
AB  - WRKY transcription factor is one of the most important transcription factor
      families widely existing in higher plants, which playing critical role in plant
      morphogenesis, development, biotic (including phytopathogens, pests etc.) and
      abiotic (drought, salt, chilling, high temperature, etc.) stress. In the present
      work, primers used to amplify full-length gene encoding WRKY transcription factor
      were designed based on the transcriptome data of P. ginseng that induced by
      benzoic acid, one of the most important autotoxins identified from root exudates
      and rhizosphere soil of P. ginseng. Then, a WRKY gene, temporarily named as
      WRKY7, was confirmed by RT-RCR. Furthermore, sequencing and sequence analysis of
      WRKY7 was conducted. Results indicated that, the full length cDNA of WRKY7 was 1
      216 bp, the open reading frame (ORF) of which was 1 014 bp, encodes 337 amino
      acids. Homologous analysis and phylogenetic tree showed that, WRKY7 belonged to
      the III category of WRKY families, which showing 87% similarity to WRKY6 in P.
      quinquefolius. Real-time PCR results showed that the expression of WRKY7 in P.
      ginseng induced by benzoic acid was up-regulated markedly than the control, so we
      speculated that WRKY7 was involved in the response to benzoic acid stress, which
      will be helpful for further research on the molecular mechanism of ginseng plant
      response to benzoic acid stress.

PMID- 29027427
TI  - [Development and evaluation of a rapid PCR detection kit for Ophiocordyceps
      sinensis].
AB  - Ophiocordyceps sinensis is a valuable traditional Chinese medicine. Due to
      resource shortage, expensive price and huge market demand, there are many
      adulterants of O. sinensis in markets. Therefore, it is necessary to establish a
      rapid and effective method for distinguishing O. sinensis. Based on the species
      specific PCR of O. sinensis, this study developed a detection kit by optimizing
      the components and evaluated the specificity, detection limit, repeatability and
      shelf life of the kit. The results showed that when the quality of O. sinensis
      accounted for more than 1/200 of that mixture, it could be detected successfully.
      Moreover, only O. sinensis could be amplified and glowed bright green
      fluorescence under ultraviolet light. The kit was still in effect when it was
      placed at 37 C for three days, which indicated that it was stable and effective
      for one year stored in 4 C. The kit in the same batch under different operation
      conditions, and in different batch under the same operation conditions gave the
      same result and accuracy, which showed good repeatability of the kit. It is
      simple, rapid and accurate to distinguish O. sinensis from its adulterants using
      the kit, and lays the foundation for commercialization of traditional Chinese
      medicine fast detection kit.

PMID- 29027429
TI  - [A new phenethyl alcohol glycoside from Orobanche coerulescens].
AB  - The constituents of the whole plant of Orobanche coerulescens were isolated and
      purified by using various column chromatographic techniques including D101,
      silica gel and ODS. The structures were identified by spectroscopic analyses
      including NMR and MS. A new phenylethanol glycoside was isolated from the whole
      plant of O. coerulescens, and was identified as 2-(3-methoxy-4-hydroxyphenyl)
      ethanol-1-O- [(1->3)-O-alpha-L-rhamnopyranosyl-4, 6-O-di-feruloyl]-beta-D
      glucopyranoside, named as orobancheoside B. Through the antibacterial activity
      test, orobancheoside B was proved to have certain antibacterial activity, and be
      one of the main active components of O. coerulescens. The research result will
      laid a foundation for the medicinal materials and quality control research.
      Activity screening, broomrape orobancheoside B has certain antibacterial
      activity, as one of the main active components of O. coerulescens, and to
      constantly improve the quality of the medicinal materials laid a foundation.

PMID- 29027430
TI  - [Virtual screening of anti-angiogenesis flavonoids from Sophora flavescens].
AB  - Angiogenesis is a dynamic, multi-step process. It is known that about 70 diseases
      are related to angiogenesis. Both the experimental and the literature reports
      showed that Sophora flavescens inhibit angiogenesis significantly, but the
      material basis and the mechanism of action have not been clear. In this study,
      molecular docking was used for screening of anti-angiogenesis flavonoids from the
      roots of S. flavescens. One handred and twenty-six flavonoids selected from S.
      flavescens were screened in the docking ligand database with six targets(VEGF
      a,TEK,KDR,Flt1,FGFR1 and FGFR2) as the receptors. In addition, the small-molecule
      approved drugs of targets from DrugBank database were set as a reference with
      minimum score of each target's approved drugs as threshold. The LibDock module in
      Discovery Studio 2.5 (DS2.5) software was applied to screen the compounds. As a
      result, 37 compounds were screened out that their scores were higher than the
      minimum score of approved drugs as well as being in the top of 10%. At last the
      mechanism of flavonoids anti-angiogenesis was preliminarily revealed, which
      provided a new method for the development of angiogenesis inhibitor drugs.

PMID- 29027431
TI  - [Determination of three saponins in rhizoma and fibrous root of Trillium
      tschonoskii and Trillium kamtschaticum].
AB  - To compare the differences of main components between in rhizoma and fibrous root
      of Trillium tschonoskii and T. kamtschaticum, a simple, accurate and reliable
      high performance liquid chromatography coupled with the charged aerosol detector
      (HPLC-CAD) method was developed and then successfully applied for simultaneous
      quantitative analysis of three compounds, including polyphyllin VII
      (T1),pennogenin 3-O-alpha-L-rhamnopyranosyl-(1->2) [alpha-L-rhamnopyranosyl-(1
      >4)]-beta-D-glucopyranoside (T2),polyphyllin VI (T3), in 16 batches of rhizome
      and 14 batches of fibrous root. The analytes were well separated from other
      constituents on TSK gel ODS (4.6 mm*250 mm, 5 MUm) with acetonitrile-water
      (43?57) at a flow rate of 1.0 mL*min-1. The injection volume was 20 MUL. The
      nitrogen inlet pressure for the CAD system was 35 psi and the nebulizer chamber
      temperature was 35 C.The method was validated for linearity (r>0.999 0), intra
      and inter-day precision (0.29%-3.0%), repeatability (0.45%-1.4%), stability (1.9%
      2.6%), recovery (100.1%-100.2%, 1.2%-1.8%), limits of detection (0.002 g*L-1),
      and limits of quantification (0.005 g*L-1).The obtained datasets were processed
      by principal component analysis (PCA) and it showed that there was almost no
      difference in rhizoma of T. tschonoskii and T. kamtschaticum from different areas
      of China. However, the 3 major compounds existed in rhizoma were different from
      those in fibrous root of T. tschonoskii and T. kamtschaticum.

PMID- 29027432
TI  - [Simultaneous determination of amino acids and nucleosides of three species in
      Termitomyces by UFLC-QTRAP-MS-MS].
AB  - A comprehensive analytical method based on UFLC-QTRAP-MS-MS was developed for the
      simultaneous determination of 15 kinds of amino acids and 12 kinds of nucleosides
      of three species in Termitomyces. The separation was carried out on a Waters
      XBridge Amide column (2.1 mm*100 mm,3.5 MUm) with gradient elution of mobile
      phase of 0.2% formic acid in water-0.2% formic acid in acetonitrile at a flow
      rate of 0.6 mL*min-1, and column temperature was maintained at 30 C. The target
      compounds were analyzed by the positive ion multiple reaction monitoring (MRM)
      mode. The principal component analysis(PCA) was made to standardized treatment
      for the comprehensive evaluation of different species in Termitomyces. The 15
      kinds of amino acids and 12 kinds of nucleosides multiple constituents showed
      good linearity (r>0.997 3) in the range of the tested concentration.The average
      recoveries ranged from 95.14% to 105.0%,and the relative standard deviations were
      less than 5.0%. The comprehensive evaluation index obtained with PCA showed that
      the Termitomyces albuminosus was significantly higher than others in amino acids
      and in nucleosides, of which the T. aurantiacus was the best. The developed
      method with good repeatability and accuracy was suitable for the simultaneous
      determination of multiple functional substances,which provided a new basis for
      the comprehensive assessment and overall control of the quality of Termitomyces
      fungi.

PMID- 29027433
TI  - [Inhibitory mechanisms of timosaponin AIII on proliferation and growth of human
      glioblastoma cells].
AB  - To explore the inhibitory effect of timosaponin AIII on the proliferation of
      human glioblastoma cell line U87MG and investigate its related mechanism. As
      compared with the model group, the tumor weight was significantly reduced in
      timosaponin AIII-treated group. Timosaponin AIIIinhibited the proliferation of
      U87MG cell line in a dose-dependent manner. It up-regulated the gene and protein
      expression levels of p21, meanwhile inhibited the protein expression levels of
      beta-Catenin, Cyclin D1 and Bcl-2. It also inhibited the translocation of beta
      Catenin into nucleus, suppressed the phosphorylation expression of ERK, but
      increased the phosphorylation expression of p38 and JNK. Combined use of JNK
      inhibitor SP600125 and p38 inhibitor SB203580 could decrease p21 and increase
      beta-Catenin protein expressions. Timosaponin AIII inhibited the proliferation of
      human glioblastoma cell line U87MG partly by intervening MAPK and Wnt/beta
      Catenin signal pathways.

PMID- 29027434
TI  - [Protective effect of notoginsenoside R1 on neuron injury induced by OGD/R
      through ATF6/Akt signaling pathway].
AB  - Notoginsenoside R1(NGR1),a critical compound in traditional herb Panax
      notoginseng, is a kind of estrogen receptor agonist.It is reported to exhibit
      anti-apoptotic,anti-oxidative and anti-inflammatory properties activity, so it is
      widely used for treatment of various diseases.In order to investigate the
      potential neuroprotective effect of NGR1 in hypoxic-ischemic brain damage(HIBD),
      primary cortical neurons were used in this study to establish oxygen-glucose
      deprivation/reoxygenation(OGD/R) injury models. They were treated with NGR1 and
      estrogen receptor inhibitor ICI-182780 respectively, then the neuronal survival,
      cell membrane integrity and apoptosis were assessed by MTT assay,lactate
      dehydrogenase test(LDH) and Hoechst 33342 stain respectively, while the protein
      expression levels of ATF6alpha,p-Akt,Akt,Bax and Cleaved Caspase-3 were measured
      by Western blotting. Results indicated that as compared with the blank control
      group,OGD/R could induce cell injury and apoptosis(P<0.05), reduce relative
      integrity of cell membrane(P<0.05), decrease protein expression of ATF6alpha,p
      Akt(P<0.05), and increase protein expression of Bax and Cleaved Caspase-3(P<0.05)
      in the primary cortical cells. After NGR1 treatment, the expression levels of
      ATF6alpha,p-Akt were obviously increased, and the expression levels of Bax and
      Cleaved Caspase-3 and the apoptosis of neuron were decreased(P<0.05). However,
      these neuroprotective properties of NGR1 against ODG/R-induced cell damage could
      be blocked by ICI-182780. This finding indicated that NGR1 may protect the
      primary cortical neurons against OGD/R induced injury,and the mechanism may be
      associated with accelerating the activation of the ATF6/Akt signaling pathway via
      estrogen receptors.

PMID- 29027435
TI  - [Preliminary establishment of integration of Alzheimer's disease and blood stasis
      syndrome tree shrew model and evaluation of intervention of Panax notoginseng
      saponins].
AB  - To establish the integration of Alzheimer's disease(AD) and blood stasis syndrome
      tree shrew model. Panax notoginseng saponins (PNS) was used to intervene the
      model to testify the stability of the model. The level of blood stasis of each
      group in the tree shrew model was evaluated by analyzing five traditional Chinese
      medicine(TCM) characterizations, four blood coagulation indexes, plasma nitric
      oxide (NO) level, plasma superoxide dismutase (SOD) level in each group.
      Hematoxylin and eosin(HE) staining was used to observe the morphological changes
      of brain hippocampal neuron cell of each group. Immunohistochemical staining was
      used to assay the ChAT and SYP levels in brain hippocampus of each group.The
      blood stasis characterization of the integration of disease and syndrome group
      was more obvious than the AD group, and that of the drug administration group was
      lower than that of the integration of disease and syndrome group. Abeta1-42, APP,
      P-Tau, ChAT and SYP level of AD group were lower than those in the blank group,
      which were further reduced in the model of integration of disease and syndrome.
      However, the administration of PNS relieved the reduction, indicating that the AD
      and blood stasis integration syndrome tree shrew model is stable.

PMID- 29027436
TI  - [Protective effect of earthworm active ingredients against endoplasmic reticulum
      stress-induced acute liver injury in mice].
AB  - To study the protective effect of earthworm active ingredients(EWAs) against
      endoplasmic reticulum stress(ERS)-induced acute liver injury in mice. The model
      of liver injury was induced through intraperitoneal injection of 10%CCl4. Serum
      glutamic-pyruvic transaminase(ALT), glutamic-oxaloacetic transaminase(AST),
      superoxide dismutase(SOD) and glutathione peroxidase(GSH-PX) activity and
      malondialdehyde(MDA) concentration were detected by colorimetric method.
      Histological examination was performed through hematoxylin-eosin staining and
      light microscopy, and apoptosis was detected using terminal transferase dUTP nick
      end labeling. The expressions of ERS related proteins, including glucose
      regulated protein 78(GRP78), protein kinase R-like ER kinase(PERK), eukaryotic
      transcription initiation factor 2alpha(eIF2alpha), active transcription factor
      4(ATF4) and CCAAT/enhancer binding homologous protein(CHOP), were measured by
      immunohistochemistry and Western blot. According to the results, compared with
      the model group,serological indexes in the high, middle and low doses of EWAs
      were significantly improved (P<0.05 or P<0.01), the extent of liver lesion was
      decreased and the degree of injury was significantly reduced, and that the liver
      index and the spleen index of mice were significantly changed(P<0.05 or P<0.01).
      In liver tissue, the expressions of GRP78 and CHOP were significantly
      decreased(P<0.05 or P<0.01). The protein expressions of GRP78, CHOP and its
      upstream signaling pathway PERK-eIF2-ATF4 were significantly decreased in each
      dose group(P<0.05 or P<0.01). In summary, EWAs has a significant protective
      effect on ERS-induced acute liver injury, and its mechanism may be correlated
      with the inhibition of oxidative stress and ERS, and down-regulation of ERS
      marker protein CHOP expression, andinhibition of apoptosis.

PMID- 29027437
TI  - [Rhaponticum uniflorum inhibits H2O2-induced apoptosis of liver cells via JNK and
      NF-kappaB pathways].
AB  - To study the inhibitory effect of Rhaponticum uniflorum on apoptosis induced by
      H2O2 in HepG2 cells. Human HepG2 cells injury models were established by H2O2,
      then cell survival rate was assayed by MTT method; levels of LDH, ALT, and AST
      were detected by chemical colorimetric method;SOD activity was detected by
      xanthine oxidase method; GSH content was detected by dithio-bis-nitrobenzoic
      acid(DTNB); MDA level was detected by thiobarbituric acid (TBA) method;and the
      relative activities of Caspase-3, 8 and 9 were measured by Colorimetry. The
      expression levels of Cleaved Caspase-3(Casp-3), cytochrome(Cyto c), NF-kappaB,
      ERK, JNK, p38 MAPK, as well as the phospharylated proteins were determined with
      Western blotting method. The results showed that R. unifloru had no significant
      effect on cell viabilities of HepG2 cells at the concentrations of 25-400 mg*L-1.
      However, H2O2decreased the cell viabilities, increased the cellular oxidative
      stress, and up-regulated the protein expressions of Casp-3, cytoplasmic Cyto c, p
      JNK and nuclear NF-kappaB. As compared with the model group,R. unifloru could
      increase the cell viability, reduce LDH, ALT and AST leakage, reduce the MDA
      formation, increase the SOD and GSH levels,reduce the relative activities of
      Caspase-3, 8 and 9, down-regulated the protein expressions of Casp-3 and
      cytoplasmic Cyto c, and down-regulate the p-JNK and nuclear NF-kappaB levels.The
      results indicated that R. unifloru had the inhibitory effect on apoptosis induced
      by H2O2in HepG2 cells, and the mechanism maybe associated with inhibiting JNK
      activation and NF-kappaB nuclear translocation.

PMID- 29027438
TI  - [Meta-analysis on indirect comparison of Erigeron breviscapus injection and
      Breviscapus injection in treatment of acute ischemic stroke].
AB  - Erigeron breviscapus injection(DZXI) and Breviscapus injection(DZSI) are two
      popular injections in treatment of acute ischemic stroke in China. Both of them
      are manufactured from a same herbal medicine, E. breviscapus, but DZXI is an
      herbal extract(mixture) preparation and DZSI is a pure compound injection. This
      article was aimed to systemically evaluate and compare their efficacy and safety
      in treatment of acute ischemic stroke. The randomized controlled trials(RCTs)
      were collected for comparing DZXI and DZSI with Salvia miltiorrhiza
      injection(FDI) as the medium, and they were compared with indirect Meta
      analysis(ITC). Thirty-nine RCTs with 4 180 patients were included. Meta-analysis
      results showed that both DZXI and DZSI had better efficacy than FDI in acute
      ischemic stroke. In the indirect comparison, DZSI had a higher total efficacy
      than DZXI, with significantly statistical differences[OR=0.634, 95%CI =
      (0.432,0.928), P<0.000 01], but there was no significant difference in
      improvement of neurological deficit [MD=-1.19, 95%CI=(-3.57,1.19), P=0.953]. On
      the safety aspect, adverse reaction rate of DZXI was 1.14%, mainly including head
      swelling, fever and chills while DZSI had no significant adverse reactions. The
      limited evidences in this study showed that Breviscapine injection had higher
      total efficiency and safety than E. breviscapine injection, but due to the low
      quality of the included RCTs, these two medicines should be comprehensively
      compared in further high-quality clinical trials.

PMID- 29027439
TI  - [Resource investigation about Tibetan medicine Rhodiola kirilowii].
AB  - The investigation aims to better understand the resource status of Rhodiola
      kirilowii, analysis the suitable habitat of wild Rh. kirilowii and protect the
      wild resources of Rh. Kirilowii, promoting the sustainable utilization of Rh.
      kirilowii resources. In this paper, we investigated the wild resources of Rh.
      kirilowii in 16 counties of Sichuan, Qinghai, Gansu and Yunnan by means of
      investigation and sampling investigation combined with interview. The results
      showed that the population densities of wild Rh. kirilowii in 4 provinces were
      very different and the reserve of wild resources decreased gradually in many
      areas. According to the survey results, the current total reserve of Rh.
      kirilowii in four provinces was about 1 100 t. The reserve of wild Rh. kirilowii
      in Sichuan province was the largest. Simultaneously, the Rh. kirilowii had a
      certain ecological value. We found that a sand control base with planting Rh.
      kirilowii was set up in Hongyuan County of Sichuan Aba Tibetan and Qiang
      Autonomous Prefecture. The investigation provides a scientific basis for the
      development and sustainable utilization of Rh. kirilowii resources.

PMID- 29027440
TI  - [Analysis on composition principles of Tibetan medicine containing Terminalia
      chebula by data mining].
AB  - This study using traditional Chinese medicine inheritance support
      software(TCMISS) to analyze the prescription rules of Tibetan medicine containing
      Terminalia chebula in the Encyclopedia of Chinese Medicine-Tibetan Medicine,
      Tibetan Medicine Composition Preparation of Modern Research and Clinical
      Application and Common Interpretation of Tibetan Medicine and so on. TCMISS(V2.5)
      was used to build a prescription database of Tibetan medicine containing T.
      chebula.The software statistical statement module, association rules and improved
      mutual information method and other data mining technologies were adopted to
      analyze the common herbs, combination rules and core combination of prescriptions
      containing T. chebula.Total 502 prescriptions containing T. chebula were analyzed
      and 14 common herbal combinations were summarized, whose ingredients mostly had
      the functions of clearing heat and detoxicating, promoting blood circulation and
      stopping pain, warming the middle-jiao and promoting the circulation of Qi.
      Prescriptions containing T. chebula were commonly used to treat 640 kinds of
      diseases, there are 22 kinds with high frequency(>=12) in which the
      representative "Tripa" disease, antiquated febrile symptoms, food poisoning had
      the highest frequency.T. chebula had different therapeutic effects through
      different compatibility.The complex composing and medication regularities of
      Tibetan medicine containing T. chebula have been clarified by TCMISS. That will
      provide reference for the clinical application of T. chebula and the new
      development.

PMID- 29027441
TI  - [Progress of stress-induced flowering in plants].
AB  - Plants tend to flower earlier if placed under stress conditions. Those stress
      factors include drought, high salinity, low temperature, high- or low-intensity
      light, and ultraviolet light. This phenomenon has been called stress-induced
      flowering. Stress-induced plant flowering might be helpful for species
      preservation. Thus, stress-induced flowering might have biological significance
      and should be considered as important as other plant flowering control strategy.
      Here, history of stress-induced flowering, metabolic regulation and molecular
      regulation mechanisms in plants were reviewed. Potential perspective was
      discussed.

PMID- 29027442
TI  - [Progress and prospect of bio-jet fuels industry in domestic and overseas].
AB  - We reviewed the progress of the bio-jet fuels industry in recent years and
      systematically analyzed the technical routes that have been approved or in the
      pipeline for approval by ASTM D7566. In addition, we highlighted a novel pathway
      to produce drop-in fuel by near-critical hydrolysis of waste cooking oils or
      algal oils followed by catalytic decarboxylation. Also, we introduced the source
      of oils and fats feedstock and the domestic bio-jet fuel industry status during
      the 12th Five-Year-Plan period. Based on our own research, we discussed the
      prospect of the bio-jet fuel industry and future research needs.

PMID- 29027443
TI  - [Gene regulatory network of hepatocellular carcinoma: a review].
AB  - Hepatocellular carcinoma (HCC) is one of the common malignant tumors. HCC gene
      regulatory network (HCC GRN), whose nodes consist of genes, miRNAs or TFs and
      whose edges consist of interaction relationships of nodes, is one of the
      important ways to study molecular mechanism of HCC. Based on various experimental
      data, types of HCC GRNs could be conducted such as TF-miRNA regulatory network.
      Integrating the studies of HCC GRN, TF-miRNA transcriptional regulatory network
      performs better in identifying core genes which play important roles in network
      disturbances. It is a trend that gene variations and transcriptional regulatory
      networks should be combined, however the corresponding research is almost blank.
      This review summarizes the source of HCC data sources, the classification,
      character, and research program of HCC GRN. Finally, according to present
      analysis and discussion of progress and research status of HCC GRN, we provide a
      useful reference for researchers.

PMID- 29027444
TI  - [Progress in microbial production of prodigiosin].
AB  - Prodigiosin is an important natural red pigment that is produced as a secondary
      metabolite by microorganisms, and has great potential applications in the field
      of pharmaceutical development, environmental management and dye preparation. This
      paper reviews recent research progress in the production of prodigiosin by
      microbial fermentation, including discovery and modification of the prodigiosin
      producing microorganisms, regulation and optimization of prodigiosin fermentation
      and extraction process, and resolution of biosynthetic pathway of prodigiosin and
      related transcriptional regulation. Finally, we discussed the future research
      directions in microbial production of prodigiosin.

PMID- 29027446
TI  - [Interactions of aminoglycosides with RNAs and proteins via carbohydrate
      microarray].
AB  - Aminoglycosides are broad-spectrum antibacterials to treat bacterial infections,
      especially gram-negative bacteria infections. However, aminoglycosides are losing
      efficacy because of the increase in antibiotic resistance and their inherent
      toxicity, attracting more interests in developing new aminoglycosides. Several
      clinically used aminoglycosides are mainly exerted by inhibition of protein
      synthesis through binding to bacterial rRNA. The bacterial ribosome RNA is the
      most currently exploited RNA drug target. Identification of new compounds that
      target RNAs is indispensable to fight with the growing threat that bacteria pose
      to human safety. In this work, we used carbohydrate microarrays to probe
      interactions of low molecular weight ligands with RNAs and proteins. Carbohydrate
      microarrays, comprising hundreds to thousands of different glycan structures on
      surfaces in a spatially discrete pattern, are sensitive and versatile tools to
      study the interactions between biological macromolecules. Herein, aminoglycosides
      have been immobilized onto the modified glass microscope slides and their
      interactions with RNAs and proteins are then measured through the labeled
      fluorescence. The results displayed that microarray can be used to detect the
      binding of aminoglycosides with three types of target molecules, including the
      small RNA oligonucleotide mimics of aminoglycoside binding sites in the ribosome
      (rRNA A-site mimics), the large group I ribozyme RNA (approximately 400
      nucleotide) and certain proteins (toxicity-causing enzymes, such as DNA
      polymerase and phospholipase C). For rRNA A-site mimics, the fluorescence
      intensities of 16S rRNA is stronger than that of 18S rRNA, illustrating that as a
      screen technique, the microarray method can not only determine the binding
      affinity to RNA but also detect the specific binding to bacterial rRNA mimic. The
      ability to screen group I ribozyme RNA can be helpful to the discovery of new RNA
      therapeutic targets. Binding of immobilized aminoglycosides to toxicity-causing
      proteins (DNA polymerase and phospholipase C) is a new method to study of
      aminoglycoside toxicity. These studies lay the foundation for rapid
      identification of new RNA-binding ligands with strong and specific binding
      affinity for their desired targets.

PMID- 29027445
TI  - [Analysis of immobilized L-glutamate oxidase fused with cellulose binding domain
      on microcrystalline cellulose].
AB  - Immobilization of enzymes is important and widely applied in biocatalysis.
      Streptomyces platensis gene gox, encoding an extracellular L-glutamate oxidase
      (Gox), was fused to cellulose binding domain (CBDcex) from Cellulomonas fimi and
      the recombinant protein Gox-CBD was expressed in Escherichia coli. The fusion
      protein (Gox-CBD) was immobilized onto microcrystalline cellulose. The
      preparation conditions, binding capacity, properties and stability of the
      immobilized enzyme were studied. Under the condition of 4 C, for 1 hour, the
      fusion protein Gox-CBD was able to bind microcrystalline cellulose at a ratio of
      9.0 mg of protein per gram of microcrystalline cellulose. Enzymatic properties of
      free and immobilized L-glutamic oxidase (Gox-CBD) were compared. The specific
      activity of the immobilized enzyme decreased, but its thermal stability increased
      a lot compared with that of the free Gox-CBD. After incubation at 60 C for 30
      min, 70% of the total activity remained whereas the free recombinant Gox
      completely lost its activity. The immobilized protein was tightly bound to
      microcrystalline cellulose at pH below 10 or more than 5 mmol/L NaCl. The fusion
      protein of Gox-CBD can be specifically immobilized on the microcrystalline
      cellulose on a single step. Therefore, our findings can provide a novel strategy
      for protein purification and enzyme immobilization.

PMID- 29027447
TI  - [Influence of expressing IrrE from Deinococcus radiodurans on osmotic stress
      tolerance of succinate-producing Escherichia coli].
AB  - Hyper-osmotic stress is one of the key factors that decrease the efficiency of
      biological succinic acid production. To increase the osmotic stress tolerance of
      succinate-producing Escherichia coli, we studied the influence of IrrE, an
      exogenous global regulator, on cell osmotic stress resistance. Fermentation
      results showed that cell growth and succinic acid production by the recombinant
      increased under different Na+ concentrations. Meanwhile, the maximum dry cell
      mass, glucose consumption and succinic acid concentration increased 15.6%, 22%
      and 23%, respectively, when fermented in a 5-L bioreactor. Expressing IrrE
      improved cell resistance to hyper-osmotic stress. Further comparison of
      intracellular osmoprotectants (trehalose and glycerol) concentrations showed that
      trehalose and glycerol concentrations in the recombinant increased. This
      suggested that introduction of IrrE could enhance intracellular osmoprotectants
      accumulation which conferred cell with improved resistance to osmotic stress.

PMID- 29027448
TI  - [Gene optimization and efficient expression of Trichoderma reesei Cel5A in Pichia
      pastoris].
AB  - Deficient activity of endo-1,4-beta-glucanase II (Cel5A) secreted by Trichoderma
      reesei is one of the challenges involved in effective cellulase saccharification
      of cellulosic substrates. Therefore, we expressed Cel5A in Pichia pastoris by
      constructing a recombinant strain. With the gene optimization based on codon
      bias, and the construction of expression vector pPIC9K-eg2, the optimized gene
      was electro-transformed into P. pastoris GS115 to form transformants. Then, a
      high Cel5A activity producing recombinant, namely P. pastoris GS115-EG II, was
      selected on G-418 resistant plates, followed by shake-flask cultivation. Enzyme
      characterization showed that the recombinant Cel5A reacted optimally at pH 4.5
      and 60 C, with 50 kDa of molecular weight, preferentially degrading amorphous
      cellulose. Recombinant Cel5A was not significantly different from the native T.
      reesei Cel5A. Moreover, a shake-flask fermentation of the recombinant strain was
      optimized as below: incubation temperature 28 C, initial pH 5.0, inoculum volume
      2%, methanol addition (per 24 h) 1.5% (V/V), sorbitol addition (per 24 h) 4 g/L
      and Tween 80 4 g/L. Under above optimized condition, the recombinant produced
      24.0 U/mL of the Cel5A after 192 h fermentation. When incubated in a 5 L
      fermentation, Cel5A enzyme activity reached 270.9 U/mL at 180 h, with 4.16 g/L of
      the total protein. The study indicates that the recombinant strain P. pastoris
      GS115-EG II is extremely suitable for heterologous expression of T. reesei
      cellulase Cel5A. And the recombinant Cel5A can be used as an alternative to the
      native T. reesei Cel5A in development of a commercially relevant enzyme based
      biorefinery process.

PMID- 29027449
TI  - [Soluble expression, purification and structural analysis of the bHLH
      transcription factor Bmsage of Bombyx mori].
AB  - Basic helix loop helix (bHLH) transcription factor plays an important role in
      biological processes. Bmsage is a class of bHLH transcription factor highly
      expressed in the silk gland of Bombyx mori, which is not only involved in the
      developmental regulation of the silk gland cells at the embryonic period, but
      also plays a crucial regulatory role during the synthesis of silk protein.
      However, currently, much of the property and structure of Bmsage is still
      remained unknown. To study the property, structure and biological role of Bmsage,
      we constructed several prokaryotic expression vectors of Bmsage fused with NusA,
      MBP, SUMO, Trx and His tags, respectively, then screened and determined the best
      soluble expression vector and condition of Bmsage in Escherichia coli combining
      with the induction temperature and IPTG concentration, and further purified the
      recombinant Bmsage by Ni-column affinity chromatography according to the
      established expression condition and characterized its secondary structure using
      circular dichroism spectra. The results showed that NusA and MBP could
      significantly enhance the soluble expression of Bmsage in E. coli, but it was
      difficult to separate Bmsage from these tags. SUMO could not only increase the
      soluble expression of Bmsage in E. coli to a certain degree, but also be
      effectively separated from Bmsage. Other tags did not effectively promote the
      soluble expression of Bmsage in E. coli. Circular dichroism spectra showed that
      the purified Bmsage had well-defined alpha-helix structure in solution,
      indicating that SUMO may promote the correct folding of Bmsage into native-like
      structure. These work not only establish a foundation for further study of the
      property, structure and function of Bmsage, but also provide a reference for the
      expression and purification of other similar proteins.

PMID- 29027450
TI  - [Cloning and expression of scavenger receptor class B BmSCRB8 in silkworm Bombyx
      mori].
AB  - Scavenger receptor class B is involved in various indispensable physiological
      processes, like the formation and inhibition of atherosclerosis or other
      cardiovascular diseases, innate immune defense and the removal of apoptotic
      cells. Here, we cloned BmSCRB8, a member of scavenger receptor class B in
      silkworm. We obtained the full-length cDNA sequence of BmSCRB8 by rapid
      amplification of cDNA ends (RACE), including 2 668 bp. The ORF of BmSCRB8 is 1
      704 bp, encoding 567 amino acids. Online software prediction indicated that the
      molecular weight of BmSCRB8 is 63.87 kDa and the isoelectric point (pI) is 6.06.
      The space-time expression profile of BmSCRB8 was detected by reverse
      transcription PCR (RT-PCR), which implicated that BmSCRB8 is extensively
      expressed in each tissue and at each stage of blood. In addition, BmSCRB8 is
      highest expressed in fat body of silkworm, and is highly expressed in
      metamorphosis periods. Anti-BmSCRB8 polyclonal antibody was generated through
      prokaryotic expression, protein purification and mice immunization.
      Simultaneously, we constructed BmSCRB8 eukaryotic vector and then transfected
      embryonic cell line of silkworm. Immunofluorescence and overexpression showed
      that BmSCRB8 expressed specifically in membrane. Western blotting demonstrated
      that BmSCRB8 protein can be specifically recognized by anti-serum generated after
      mice immunization.

PMID- 29027452
TI  - [Expression and activity assay of recombinant flap endonuclease 1].
AB  - Flap endonuclease 1 (FEN1) is an endonuclease that catalyzes invasive reaction.
      It can be used in signal-amplification reaction-based nucleic acid assay.
      However, the application of FEN1 is hampered due to the lack of detailed
      protocols to express and purify the enzyme, and to quantify the enzyme activity.
      In this paper, the DNA fragment coding the gene of FEN1 from Archaeoglobus
      fulgidus was synthesized, and inserted into the plasmid of pET24a(+) to express
      recombinant FEN1 with His-tag. After optimizing the expression, detailed
      expression protocol of FEN1 was obtained by culturing the recombinant E. coli at
      37 C with 200 r/min of shaking for 8 h, followed by inducing with 0.05 mmol/L
      IPTG at 37 C for 11 h. The purified recombinant FEN1 with the molecular mass of
      38 kDa was obtained by Ni-affinity chromatography. Moreover, we developed a
      accurate quantification method with fluorescence-labelled probes. Finally, the
      recombinant FEN1 was used in real-time PCR coupled with high specific invader
      assay for aldh2 gene genotyping to obtain the correct typing results, indicating
      that the recombinant FEN1 can be used in gene polymorphism detection. We provide
      a reliable enzyme for developing invasive reaction-based nucleic acid assay.

PMID- 29027451
TI  - [Enhancing the ability of autophagy and proliferation of bone marrow mesenchymal
      stem cells by interleukin-8 through Akt-STAT3 pathway in hypoxic environment].
AB  - To study the effects and mechanisms of interleukin-8 (IL-8) on the proliferation
      and autophagy of human bone marrow mesenchymal stem cells (hBMSC) under hypoxic
      condition. In the hypoxia model, we set the non-stimulated hBMSC as the hypoxia
      control group; the hBMSC stimulated by 100 MUmol/L human IL-8 as the IL-8 group;
      the hBMSC stimulated by 50 MUmol/L MK2206 (Akt protein inhibitor) and 100MUmol/L
      IL-8 as the Akt inhibitor group; and the normal cultured hBMSC as the normal
      control group. The experiments of EdU cell proliferation and TUNEL apoptosis were
      respectively used to detect the number of positive cells that were labeled by EdU
      and apoptosis in each group, and Western blotting and ELISA were used
      respectively to detect the expression of autophagy protein (LC-3), Akt/STAT3 and
      other proteins in each group. The results indicated that the proliferation and
      autophagy of hBMSC in IL-8 group was higher than that in hypoxia control group
      and Akt inhibitor group, and the apoptosis rate in IL-8 group decreased. These
      results and the high expression of Akt, STAT3 and VEGF protein of IL-8 group show
      that under the hypoxic condition, IL-8 played a protective role on MSC through
      the Akt-STAT3 pathway. It had important significance in the protection of MSC
      against the injury due to ischemia and hypoxia, and promoted the application of
      MSC in regenerative medicine.

PMID- 29027453
TI  - [Ubiquitinated proteomics research of Hep3B].
AB  - Ubiquitination is one of the most major post-translational modifications playing
      important role in regulation of intra-cellular proteins' stability, degradation,
      localization and biological activity. However, these proteins are difficult to be
      detected due to their low abundance, short half-life. In this study, ubiquitin
      binding domains (UBDs) were constructed to purify the ubiquitinated proteins from
      Hep3B cells. Ubiquitinated proteins and sites were detected by LC-MS/MS. A total
      of 1 900 potential ubiquitinated proteins were identified. Among them, 158
      ubiquitinated sites were identified, belonging to 102 proteins. Bioinformatics
      analysis revealed that the enriched pathways of ubiquitinated proteins were
      closely related to tumor occurrence and development. The dysfunction of ubiquitin
      proteasome has a high correlation with cell signaling and extracellular matrix
      changing in tumor cells.

PMID- 29027454
TI  - [Delivery of recombinant enhanced green fluorescent protein to Pichia pastoris
      cell wall directed by a mammalian nonclassical secretion signal peptide].
AB  - A mammalian nonclassical secretion sequence derived from mouse Engrailed2
      homeoprotein (En2) was used to direct the secretion of the enhanced green
      fluorescent protein from Pichia pastoris. This signal peptide conferred the
      transport of enhanced green fluorescent protein into periplasm through an
      endoplasmic reticulum-golgi independent pathway, without inducing severe unfolded
      protein response as compared with Saccharomyces cerevisae alpha-factor
      preprosequence. This study implies that this mammalian nonclassical signal
      peptide could be developed as a useful tool for delivering cargoes to the cell
      surface of yeast.

PMID- 29027455
TI  - [Construction and verification of NF-kappaB luciferase reporter gene system].
AB  - To quantify the transcriptional activity of NF-kappaB and to screen drugs related
      to the regulation of NF-kappaB activation, we constructed a recombinant plasmid
      through deleting the original CMV promoter of retrovirus vector pQCXIP and
      inserting the NF-kappaB enhancer and NanoLuc luciferase sequence into the vector.
      Then, using the recombinant plasmid we constructed a cell line in which the
      expression of NanoLuc luciferase (NLuc) was regulated by NF-kappaB. The inserted
      sequences were verified by restriction endonuclease digestion and sequencing.
      Tumor necrosis factor-alpha (TNF-alpha), an NF-kappaB activator, acted on the
      constructed NLuc cell line and leaded to the specific luciferase reaction. The
      luciferase reaction showed a fine time and dose dependence to the TNF-alpha
      stimulation, indicating the successful construction of the NF-kappaB regulated
      NLuc-expressing cell line. Besides, the NF-kappaB inhibitor, triptolide, reduced
      the expression of NLuc in a dose-dependent way. The constructed reporter system
      in this study could be applied in the quantification of the NF-kappaB
      transcriptional activity and in the NF-kappaB regulation-related drug screening.

PMID- 29027456
TI  - Highly Efficient Photocatalytic Water Splitting over Edge-Modified Phosphorene
      Nanoribbons.
AB  - Two-dimensional phosphorene with desirable optoelectronic properties (ideal band
      gap, high carrier mobility, and strong visible light absorption) is a promising
      metal-free photocatalyst for water splitting. However, the band edge positions of
      the valence band maximum (VBM) and conduction band maximum (CBM) of phosphorene
      are higher than the redox potentials in photocatalytic water splitting reactions.
      Thus, phosphorene can only be used as the photocathode for hydrogen evolution
      reaction as a low-efficiency visible-light-driven photocatalyst for hydrogen
      production in solar water splitting cells. Here, we propose a new mechanism to
      improve the photocatalytic efficiency of phosphorene nanoribbons (PNRs) by
      modifying their edges for full reactions in photocatalytic water splitting. By
      employing first-principles density functional theory calculations, we find that
      pseudohalogen (CN and OCN) passivated PNRs not only show desired VBM and CBM band
      edge positions induced by edge electric dipole layer, but also possess intrinsic
      optoelectronic properties of phosphorene, for both water oxidation and hydrogen
      reduction in photocatalytic water splitting without using extra energy.
      Furthermore, our calculations also predict that the maximum energy conversion
      efficiency of heterojunction solar cells consisting of different edge-modified
      PNRs can be as high as 20% for photocatalytic water splitting.

PMID- 29027457
TI  - Gravimetric Standard Gas Mixtures for Global Monitoring of Atmospheric SF6.
AB  - In this study, standard gas mixtures of SF6 in synthetic air were gravimetrically
      developed as a suite consisting of 6 mixtures with mole fractions of SF6 ranging
      from 5 to 15 pmol/mol. For precision in weighing the gas fills, an automatic
      weighing system coupled with a high sensitivity mass balance was used and a
      gravimetry precision of 3 mg (2sigma) was achieved. Impurity profiles of the raw
      gases were determined by various analyzers. In particular, sub pmol/mol levels of
      SF6 in the matrix components (N2, O2, and Ar) were carefully measured, since the
      mole fraction of SF6 in the final step can be significantly biased by this trace
      amount of SF6 in the raw gases of the matrix components. Gravimetric dilution of
      SF6 by purity-assessed N2 was performed in 6 steps to achieve a mole fraction of
      440 pmol/mol. In the final step, O2 and Ar were added to mimic the atmospheric
      composition. Gravimetric fractions of SF6 and the associated standard uncertainty
      in each step were computed according to the ISO 6142 and JCGM 100:2008,
      respectively, and validated experimentally. Eventually, the SF6 fraction
      uncertainty of the standard gas mixtures combined by uncertainties of gravimetric
      preparation and verification measurements were found to be nominally 0.08% at a
      95% confidence interval. A comparison with independent calibration standards from
      NOAA shows agreement within 0.49%, satisfying the extended WMO compatibility
      goal, 0.05 ppt.

PMID- 29027458
TI  - The Stringent Response Induced by Phosphate Limitation Promotes Purine Salvage in
      Agrobacterium fabrum.
AB  - Agrobacterium fabrum induces tumor growth in susceptible plant species. The
      upregulation of virulence genes that occurs when the bacterium senses plant
      derived compounds is enhanced by acidic pH and limiting inorganic phosphate.
      Nutrient starvation may also trigger the stringent response, and purine salvage
      is among the pathways expected to be favored under such conditions. We show here
      that phosphate limitation induces the stringent response, as evidenced by
      production of (p)ppGpp, and that the xdhCSML operon encoding the purine salvage
      enzyme xanthine dehydrogenase is upregulated ~15-fold. The xdhCSML operon is
      under control of the TetR family transcription factor XdhR; direct binding of
      ppGpp to XdhR attenuates DNA binding, and the enhanced xdhCSML expression
      correlates with increased cellular levels of (p)ppGpp. Xanthine dehydrogenase may
      also divert purines away from salvage pathways to form urate, the ligand for the
      transcription factor PecS, which in the plant pathogen Dickeya dadantii is a key
      regulator of virulence gene expression. However, urate levels remain low under
      conditions that produce increased levels of xdhCSML expression, and neither
      acidic pH nor limiting phosphate results in induction of genes under control of
      PecS. Instead, expression of such genes is induced only by externally
      supplemented urate. Taken together, our data indicate that purine salvage is
      favored during the stringent response induced by phosphate starvation, suggesting
      that control of this pathway may constitute a novel approach to modulating
      virulence. Because bacterial purine catabolism appears to be unaffected, as
      evidenced by the absence of urate accumulation, we further propose that the PecS
      regulon is induced by only host-derived urate.

PMID- 29027459
TI  - Plasmon-Induced Selective Oxidation Reaction at Single-Walled Carbon Nanotubes.
AB  - Local surface plasmon resonance (LSPR)-induced oxidation of semiconducting and
      metallic single-walled nanotubes (SWNTs) on the nanometer scale was investigated
      using surface-enhanced Raman scattering (SERS) measurements. An isolated SWNT was
      supported on a well-defined Au nanodimer structure that possesses an LSPR field
      at the nanogap under light irradiation, and highly intense SERS spectra of the
      SWNT at the gap region were measured. SERS analysis under O2-saturated solutions
      and the addition of reactive oxygen species inhibitors demonstrated that
      condensed singlet oxygen (1O2), which is one of the reactive oxygen species, was
      efficiently generated from a semiconducting SWNT at the nanogap by the LSPR field
      and led to the local oxidation of the tube. In contrast to the semiconducting
      SWNT, no defect formation was observed in a metallic SWNT, probably because of
      rapid quenching of the photoexcited state. This selective local defect formation
      by LSPR-induced oxidation of a semiconducting SWNT would provide novel
      nanoprocessing and nanofunctionalization methods for the fabrication of future
      SWNT-based nanodevices.

PMID- 29027460
TI  - Synthesis of Enantiopure Mixed Alkyl-Aryl Vicinal Diamines by the Diaza-Cope
      Rearrangement: A Synthesis of (+)-CP-99,994.
AB  - The stereoselective synthesis of mixed alkyl-aryl vicinal diamines was
      demonstrated by the use of 1,2-bis(2-hydroxyphenyl)-1,2-diaminoethene (hpen). A
      sequential addition of aryl and alkyl aldehyde to hpen gave a fused imidazolidine
      dihydro-1,3-oxazine ring stereoselectively, which undergoes the diaza-Cope
      rearrangement to provide mixed vicinal diimines at elevated temperature in good
      yields and excellent stereoselectivity. We also showed that (+)-CP-99,994 can be
      readily prepared by the diaza-Cope rearrangement in overall 42% yield.

PMID- 29027461
TI  - Nonpolar Resistive Switching in Ag@TiO2 Core-Shell Nanowires.
AB  - Nonpolar resistive switching (RS), a combination of bipolar and unipolar RS, is
      demonstrated for the first time in a single nanowire (NW) system. Exploiting
      Ag@TiO2 core-shell (CS) NWs synthesized by postgrowth shell formation, the
      switching mode is controlled by adjusting the current compliance effectively,
      tailoring the electrical polarity response. We demonstrate ON/OFF ratios of 105
      and 107 for bipolar and unipolar modes, respectively. In the bipolar regime,
      retention times could be controlled up to 103 s, and in the unipolar mode, >106 s
      was recorded. We show how the unique dual-mode switching behavior is enabled by
      the defect-rich polycrystalline material structure of the TiO2 shell and the
      interaction between the Ag core and the Ag electrodes. These results provide a
      foundation for engineering nonpolar RS behaviors for memory storage and
      neuromorphic applications in CSNW structures.

PMID- 29027462
TI  - Dual-Signal Microbial Biosensor for the Detection of Dopamine without Inference
      from Other Catecholamine Neurotransmitters.
AB  - Dopamine, one of catecholamine neurotransmitters, plays an important role in many
      brain functions and behavioral responses. In this study, we developed a novel
      dual-signal whole-cell biosensor for the detection of dopamine through the
      generation of red fluorescent proteins and 6-decarboxylated betaxanthin pigments.
      The proposed system responses specifically to dopamine with a detection limit of
      1.43 MUM. Furthermore, a combination of dual output signals makes it possible to
      reduce the interference from other catecholamine neurotransmitters, including L
      DOPA, epinephrine, and norepinephrine.

PMID- 29027463
TI  - Machine-Learning-Based Olfactometer: Prediction of Odor Perception from
      Physicochemical Features of Odorant Molecules.
AB  - Gas chromatography/olfactometry (GC/O) has been used in various fields as a
      valuable method to identify odor-active components from a complex mixture. Since
      human assessors are employed as detectors to obtain the olfactory perception of
      separated odorants, the GC/O technique is limited by its subjectivity,
      variability, and high cost of the trained panelists. Here, we present a proof-of
      concept model by which odor information can be obtained by machine-learning-based
      prediction from molecular parameters (MPs) of odorant molecules. The odor
      prediction models were established using a database of flavors and fragrances
      including 1026 odorants and corresponding verbal odor descriptors (ODs).
      Physicochemical parameters of the odorant molecules were acquired by use of
      molecular calculation software (DRAGON). Ten representative ODs were selected to
      build the prediction models based on their high frequency of occurrence in the
      database. The features of the MPs were extracted via either unsupervised
      (principal component analysis) or supervised (Boruta, BR) approaches and then
      used as input to calibrate machine-learning models. Predictions were performed by
      various machine-learning approaches such as support vector machine (SVM), random
      forest, and extreme learning machine. All models were optimized via parameter
      tuning and their prediction accuracies were compared. A SVM model combined with
      feature extraction by BR-C (confirmed only) was found to afford the best results
      with an accuracy of 97.08%. Validation of the models was verified by using the
      GC/O data of an apple sample for comparison between the predicted and measured
      results. The prediction models can be used as an auxiliary tool in the existing
      GC/O by suggesting possible OD candidates to the panelists and thus helping to
      give more objective and correct judgment. In addition, a machine-based GC/O in
      which the panelist is no longer needed might be expected after further
      development of the proposed odor prediction technique.

PMID- 29027464
TI  - Thermal Stability-Enhanced and High-Efficiency Planar Perovskite Solar Cells with
      Interface Passivation.
AB  - As the electron transport layer (ETL) of perovskite solar cells, oxide
      semiconductor zinc oxide (ZnO) has been attracting great attention due to its
      relatively high mobility, optical transparency, low-temperature fabrication, and
      good environment stability. However, the nature of ZnO will react with the patron
      on methylamine, which would deteriorate the performance of cells. Although many
      methods, including high-temperature annealing, doping, and surface modification,
      have been studied to improve the efficiency and stability of perovskite solar
      cells with ZnO ETL, devices remain relatively low in efficiency and stability.
      Herein, we adopted a novel multistep annealing method to deposit a porous PbI2
      film and improved the quality and uniformity of perovskite films. The cells with
      ZnO ETL were fabricated at the temperature of <150  degrees C by solution
      processing. The power conversion efficiency (PCE) of the device fabricated by the
      novel annealing method increased from 15.5 to 17.5%. To enhance the thermal
      stability of CH3NH3PbI3 (MAPbI3) on the ZnO surface, a thin layer of small
      molecule [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) was inserted between
      the ZnO layer and perovskite film. Interestingly, the PCE of PCBM-passivated
      cells could reach nearly 19.1%. To our best knowledge, this is the highest PCE
      value of ZnO-based perovskite solar cells until now. More importantly, PCBM
      modification could effectively suppress the decomposition of MAPbI3 and improve
      the thermal stability of cells. Therefore, the ZnO is a promising candidate of
      electron transport material for perovskite solar cells in future applications.

PMID- 29027466
TI  - Junction Quality of SnO2-Based Perovskite Solar Cells Investigated by Nanometer
      Scale Electrical Potential Profiling.
AB  - Electron-selective layers (ESLs) and hole-selective layers (HSLs) are critical in
      high-efficiency organic-inorganic lead halide perovskite (PS) solar cells for
      charge-carrier transport, separation, and collection. We developed a procedure to
      assess the quality of the ESL/PS junction by measuring potential distribution on
      the cross section of SnO2-based PS solar cells using Kelvin probe force
      microscopy. Using the potential profiling, we compared three types of cells made
      of different ESLs but otherwise having an identical device structure: (1) cells
      with PS deposited directly on bare fluorine-doped SnO2 (FTO)-coated glass; (2)
      cells with an intrinsic SnO2 thin layer on the top of FTO as an effective ESL;
      and (3) cells with the SnO2 ESL and adding a self-assembled monolayer (SAM) of
      fullerene. The results reveal two major potential drops or electric fields at the
      ESL/PS and PS/HSL interfaces. The electric-field ratio between the ESL/PS and
      PS/HSL interfaces increased in devices as follows: FTO < SnO2-ESL < SnO2 + SAM;
      this sequence explains the improvements of the fill factor (FF) and open-circuit
      voltage (Voc). The improvement of the FF from the FTO to SnO2-ESL cells may
      result from the reduction in voltage loss at the PS/HSL back interface and the
      improvement of Voc from the prevention of hole recombination at the ESL/PS front
      interface. The further improvements with adding an SAM is caused by the defect
      passivation at the ESL/PS interface, and hence, improvement of the junction
      quality. These nanoelectrical findings suggest possibilities for improving the
      device performance by further optimizing the SnO2-based ESL material quality and
      the ESL/PS interface.

PMID- 29027465
TI  - Multi-Stage Structural Transformations in Zero-Strain Lithium Titanate Unveiled
      by in Situ X-ray Absorption Fingerprints.
AB  - Zero-strain electrodes, such as spinel lithium titanate (Li4/3Ti5/3O4), are
      appealing for application in batteries due to their negligible volume change and
      extraordinary stability upon repeated charge/discharge cycles. On the other hand,
      this same property makes it challenging to probe their structural changes during
      the electrochemical reaction. Herein, we report in situ studies of lithiation
      driven structural transformations in Li4/3Ti5/3O4 via a combination of X-ray
      absorption spectroscopy and ab initio calculations. Based on excellent agreement
      between computational and experimental spectra of Ti K-edge, we identified key
      spectral features as fingerprints for quantitative assessment of structural
      evolution at different length scales. Results from this study indicate that,
      despite the small variation in the crystal lattice during lithiation, pronounced
      structural transformations occur in Li4/3Ti5/3O4, both locally and globally,
      giving rise to a multi-stage kinetic process involving mixed quasi-solid
      solution/macroscopic two-phase transformations over a wide range of Li
      concentrations. This work highlights the unique capability of combining in situ
      core-level spectroscopy and first-principles calculations for probing Li-ion
      intercalation in zero-strain electrodes, which is crucial to designing high
      performance electrode materials for long-life batteries.

PMID- 29027467
TI  - Synthesis of Secondary Aromatic Amides via Pd-Catalyzed Aminocarbonylation of
      Aryl Halides Using Carbamoylsilane as an Amide Source.
AB  - Using N-methoxymethyl-N-organylcarbamoyl(trimethyl)silanes as secondary amides
      source, the direct transformation of aryl halides into the corresponding
      secondary aromatic amides via palladium-catalyzed aminocarbonylation is
      described. The reactions tolerated a broad range of functional groups on the aryl
      ring except big steric hindrance of substituent. The types and the relative
      position of substituents on the aryl ring impact the coupling efficiency.

PMID- 29027468
TI  - Serrated polyposis syndrome associated with long-standing inflammatory bowel
      disease.
AB  - Inflammatory bowel disease (IBD) patients are at an increased risk of developing
      colorectal cancer (CRC), which is thought to develop via the adenoma-carcinoma
      pathway. Since the discovery of the serrated carcinogenesis pathway and serrated
      polyposis syndrome (SPS), the incidence of carcinomas arising from serrated
      lesions in IBD patients has increased. We report three cases of long-standing IBD
      patients with associated serrated polyposis syndrome. At present, the
      pathophysiology of serrated lesions in IBD patients is not fully understood and
      there is a lack of strong evidence to confirm whether the manifestation of both
      conditions represents an increased risk of developing cancer. Therefore, more
      accurate surveillance guidelines are needed and are being actively investigated
      at present.

PMID- 29027469
TI  - Bucking the current trend in bioelectrochemical systems: a case for
      bioelectroanalytics.
AB  - Turning wastewater directly into electricity is alluring, widespread use of
      microbial fuel cells (MFCs) to achieve this at industrial scale appears
      increasingly unlikely despite intense research efforts lasting over a decade.
      Such endeavors have not been futile, however, and game-changing discoveries have
      resulted from these well-intentioned, scientifically rigorous but ultimately
      frustrated attempts to resolve the Waste-Energy dichotomy. The appeal of MFCs is
      largely of conceptual elegance rather than financial competitiveness, based on
      the green ideal that bacteria can be turned into cost effective bio-batteries.
      This notion is founded on the solid principles of extracellular electron transfer
      (EET), where microbes use electrodes interchangeably with other electron
      acceptors to generate current as a direct proxy for microbial metabolism. We
      contend that a nuanced understanding of EET has been restricted by focusing on
      device performance when in fact this information could be more beneficially
      channeled into addressing analytical questions pertaining to the presence and
      activity of microorganisms across systems of environmental and medical import,
      i.e. bioelectroanalytics. We discuss here relevant literature detailing
      bioelectrochemical systems and contrast energy-centric conclusions with
      observations geared towards bioelectroanalytics. We explore the expanding
      possibilities of bioelectroanalytics enabled by advances in genetic techniques
      and rooted in the concept that microbial interactions with an electrode extend to
      more than just cells seeking alternative electron acceptors. Our intention is to
      highlight alternative directions in the field and encourage researchers to
      harness bioelectroanalytics to address wider societal problems, in addition to
      addressing climate change.

PMID- 29027470
TI  - Next generation sequencing applications for cardiovascular disease.
AB  - The Human Genome Project (HGP), as the primary sequencing of the human genome,
      lasted more than one decade to be completed using the traditional Sanger's
      method. At present, next-generation sequencing (NGS) technology could provide the
      genome sequence data in hours. NGS has also decreased the expense of sequencing;
      therefore, nowadays it is possible to carry out both whole-genome (WGS) and whole
      exome sequencing (WES) for the variations detection in patients with rare genetic
      diseases as well as complex disorders such as common cardiovascular diseases
      (CVDs). Finding new variants may contribute to establishing a risk profile for
      the pathology process of diseases. Here, recent applications of NGS in
      cardiovascular medicine are discussed; both Mendelian disorders of the
      cardiovascular system and complex genetic CVDs including inherited
      cardiomyopathy, channelopathies, stroke, coronary artery disease (CAD) and are
      considered. We also state some future use of NGS in clinical practice for
      increasing our information about the CVDs genetics and the limitations of this
      new technology. Key messages Traditional Sanger's method was the mainstay for
      Human Genome Project (HGP); Sanger sequencing has high fidelity but is slow and
      costly as compared to next generation methods. Within cardiovascular medicine,
      NGS has been shown to be successful in identifying novel causative mutations and
      in the diagnosis of Mendelian diseases which are caused by a single variant in a
      single gene. NGS has provided the opportunity to perform parallel analysis of a
      great number of genes in an unbiased approach (i.e. without knowing the
      underlying biological mechanism) which probably contribute to advance our
      knowledge regarding the pathology of complex diseases such as CVD.

PMID- 29027471
TI  - Ascribing a novel role for tmRNA of Escherichia coli in resistance to mitomycin
      C.
AB  - AIM: The ssrA mutants were found to be more sensitive to mitomycin C (MMC) and
      our aim was to study this phenomenon in detail. MATERIALS & METHODS: Strains were
      constructed by P1 transduction. pssrA+ plasmid was constructed by PCR-based
      cloning and transformation was done by CaCl2 method. Relative viability analyses
      were done to assess the extent of viability of strains in relevant conditions.
      Gram staining was used for microscopic analysis. RESULTS: ssrA mutants become
      sensitive specifically to MMC, that too in a strain-specific manner. Precise
      tagging function of SsrA is necessary for conferring resistance to MMC. sulA::kan
      restored the viability of ssrA::cat mutants in a strain-specific manner.
      CONCLUSION: This study for the first time implicates SsrA in progression of
      efficient cell division and resistance to MMC.

PMID- 29027472
TI  - Using Decisional Conflict to Evaluate Patient Engagement During Hospital
      Discharge.

PMID- 29027473
TI  - Developing Diverse Leaders at Academic Health Centers: A Prerequisite to Quality
      Health Care?

PMID- 29027474
TI  - On the metabolites produced by Colletotrichum gloeosporioides a fungus proposed
      for the Ambrosia artemisiifolia biocontrol; spectroscopic data and absolute
      configuration assignment of colletochlorin A.
AB  - Ambrosia artemisiifolia L. is responsible for serious allergies induced on
      humans. Different approaches for its control were proposed during the COST Action
      FA1203 "Sustainable management of Ambrosia artemisiifolia in Europe" (SMARTER).
      Fungal secondary metabolites often show potential herbicidal activity. Three
      phytotoxins were purified from the fungal culture filtrates of Colletotrichum
      gloeosporioides, isolated from infected leaves of A. artemisiifolia. They were
      identified by spectroscopic and chemical methods as colletochlorin A, orcinol and
      tyrosol (1, 2 and 3). The absolute configuration 6'R to colletochlorin A was
      assigned for the first time applying the advanced Mosher's method. When assayed
      by leaf-puncture on A. artemisiifolia only 1 caused the appearance of large
      necrosis. The same symptoms were also induced by 1 on ambrosia plantlets
      associated with plant wilting. On Lemna minor, colletochlorin A caused a clear
      fronds browning, with a total reduction in chlorophyll content.

PMID- 29027475
TI  - Antimould microbial and plant metabolites with potential use in intelligent food
      packaging.
AB  - Moulds food infestation is a heavy dangerous problem for human health and also
      could generate heavy economic losses. The intelligent packaging using eco
      friendly biodegradable biofilm incorporating bioactive natural safe compounds
      represents a new frontier. This manuscript reports the inhibitory activity of 12
      bacterial, fungal and plant metabolites against Penicillium roqueforti and
      Aspergillus niger. Among them alpha-costic acid and ungeremine (3 and 12) are the
      most promising as potential biofungicide against both fungal strains. They
      inhibited fungal growth by more than 60% respect to the control at 72 h and this
      activity persisted also at 96 h. Ungeremine showed MIC90 lower than 0.003 mg/mL
      after 48 h of incubation and of 0.025 mg/mL at 72 h against P. roqueforti. The
      MIC90 value for A. niger was 0.2 mg/mL at 48 h for both compounds. The alpha
      costic acid showed generally MIC values at 48 and 72 h higher than ungeremine.

PMID- 29027476
TI  - Caregiver Valuation of Chest Radiography for the Diagnosis of Pneumonia in
      Children.

PMID- 29027477
TI  - A Previsit Screening Checklist Improves Teamwork and Access to Preventive
      Services in a Medical Home Serving Low-Income Adolescent and Young Adult
      Patients.
AB  - Publicly insured adolescents and young adults experience significant obstacles in
      accessing primary care services. As a result, they often present to their medical
      appointments with multiple unmet needs, adding time and complexity to the visit.
      The goal of this project was to optimize team work and access to primary care
      services among publicly insured adolescents and young adults attending an urban
      primary care clinic, using a previsit screening checklist to identify patient
      needs and delegate tasks within a care team to coordinate access to health
      services at the time of the visit. We conducted an interventional quality
      improvement initiative in a PDSA (Plan-Do-Study-Act) cycle format; 291 patients,
      13 to 25 years old were included in the study over an 8-months period. The
      majority of patients were receptive to the previsit screening checklist; 85% of
      services requested were provided; nonclinician staff felt more involved in
      patient care; and providers' satisfaction increased.

PMID- 29027478
TI  - Educational Initiative to Standardize Concussion Management in Pediatric Primary
      Care.
AB  - Pediatric primary care providers report limited training and tools to manage
      concussion. We developed a learning community intervention for a large
      independent pediatric practice association affiliated with a university hospital
      to standardize concussion management and improve the use of consensus-based
      guidelines. The learning community included in-person and online didactics,
      followed by a web-based reinforcement platform to educate and train clinicians on
      our treatment algorithm and decision support tools. Chart reviews before and
      after the intervention demonstrated significant increases in the use of
      standardized symptom rating scales (19.6% to 69.3%; P < .001), balance assessment
      (2.3% to 37.6%; P < .001), and scheduled follow-up (41.8% to 61.2%; P < .001),
      with an increase in delivery of our entire best practice bundle from 3.5% to
      28.1% ( P < .001). A multimodal educational intervention can effect change among
      pediatric primary care providers and help align their management practices with
      consensus-based guidelines.

PMID- 29027479
TI  - Understanding Barriers to Literacy Promotion Among New Jersey General
      Pediatricians.
AB  - Low literacy is associated with poor health. We sought to examine pediatricians'
      attitudes and practices regarding literacy promotion in early childhood. We
      distributed a self-administered 23-item survey to a random sample of 500 board
      certified or eligible New Jersey primary care pediatricians. 134 surveys were
      returned, 25 of which were excluded. In all, 91% of pediatricians in our sample
      agreed that literacy promotion was an essential aspect of practice, and two
      thirds agreed that they conduct activities to promote literacy. A total of 77% of
      pediatricians who completed their training <=20 years ago agreed that they were
      adequately trained to promote literacy compared with 58% who completed their
      training >20 years ago ( P = .04). Physicians reported several barriers including
      time constraints and insufficient funding. While most pediatricians in our sample
      support literacy promotion, less conducted activities in practice. Further study
      is needed to understand how to facilitate implementation of literacy promotion
      guidelines.

PMID- 29027480
TI  - A Learning Collaborative Approach to Improve Primary Care STI Screening.
AB  - The Bronx Ongoing Pediatric Screening (BOPS) project sought to improve screening
      for sexual activity and sexually transmitted infections (gonorrhea and chlamydia
      [GCC] and HIV) in a primary care network, employing a modified learning
      collaborative, real-time clinical data feedback to practices, improvement
      coaching, and a pay-for-quality monetary incentive. Outcomes are compared for 11
      BOPS-participating sites and 10 non-participating sites. The quarterly median
      rate for documenting sexual activity status increased from 55% to 88% (BOPS
      sites) and from 13% to 74% (non-BOPS sites). GCC screening of sexually active
      youth increased at BOPS and non-BOPS sites. Screening at non-health care
      maintenance visits improved more at BOPS than non-BOPS sites. Data from
      nonparticipating sites suggests that introduction of an adolescent EMR template
      or other factors improved screening rates regardless of BOPS participation; BOPS
      activities appear to promote additional improvement of screening during non
      health maintenance visits.

PMID- 29027481
TI  - Narrowing urban-suburban rural disparities in physical growth among children in
      China: findings from the 5th national survey in 2015.
AB  - BACKGROUND: Previous studies have reported a narrowing tendency in urban-suburban
      rural differences for height, but almost no tendency of narrowing for weight in
      Chinese children between 1975-2005. AIM: To examine urban-suburban rural
      disparities for both height and weight in a recent 10-year period. SUBJECTS AND
      METHODS: A representative sample of 161,643 children under 7 years old was
      obtained from the 5th national survey conducted in urban and suburban rural areas
      of the nine cities in China in 2015. Trends in urban-suburban rural differences
      were assessed from 1975-2015. RESULTS: Generally, urban boys and girls were
      taller or heavier than their suburban rural counterparts. By 2015, there were
      almost no obvious differences for urban-suburban rural height differences for
      children under 3. Urban-suburban rural weight differences narrowed sharply in the
      10-year period. There were no obvious differences for urban-suburban rural height
      differences among the 3rd, 50th and 97th percentiles; however, the weight
      differences at the 97th percentile were larger than at the 50th percentile for
      children over 3. CONCLUSION: The narrowing urban-suburban rural disparities in
      China suggest the physical growth inequality may be eliminated, along with the
      sustained improvement of socioeconomic status and the acceleration of
      urbanisation process in suburban rural areas.

PMID- 29027482
TI  - Structural genomics of pNDM-BTR harboring In191 and Tn6360, and other bla NDM
      carrying IncN1 plasmids.
AB  - AIM: To characterize a conjugative bla NDM-1-carrying plasmid pNDM-BTR from a
      clinical Escherichia coli isolate. MATERIALS & METHODS: The complete nucleotide
      sequence of pNDM-BTR was determined using next-generation sequencing technology.
      Comparative genomic analysis of bla NDM-carrying IncN1 plasmids, including pNDM
      BTR, was performed, and the antimicrobial resistance phenotypes were determined.
      RESULTS: pNDM-BTR contained three accessory modules, namely IS26, a novel Tn3
      family transposon Tn6360 and the dfrA14 region composed of In191, ecoRII
      ecoRIImet and DeltaIS1X2. The relatively small IncN1 backbones could integrate
      massive accessory modules, most of which were integrated at two 'hotspots'. These
      IncN1 plasmids contained distinct profiles of accessory modules, which included
      those carrying various resistance genes. CONCLUSION: This study provides a deeper
      insight into horizontal transfer of resistance genes among IncN1 plasmids.

PMID- 29027483
TI  - CDK4/6 blockade in breast cancer: current experience and future perspectives.
AB  - INTRODUCTION: Dysregulated cellular proliferation, one of the hallmarks of
      cancer, is mediated by aberrant activation of the cell cycle machinery through
      the biological effects of cyclin-dependent kinases (CDKs). The clinical
      development of non-selective CDK inhibitors failed due to combined lack of
      efficacy and excessive toxicity reported by clinical trials across different
      cancer types. The clinical development of second generation, CDK4/6-selective
      inhibitors, namely palbociclib, abemaciclib and ribociclib, led to practice
      changing results in the setting of breast cancer. Areas covered: This review
      illustrates how CDK4/6-selective inhibitors got approval for the treatment of
      patients with either newly diagnosed or pretreated advanced hormone receptor
      positive, HER2-negative breast cancer. Furthermore, data about potential
      predictive biomarkers, as well as preclinical and preliminary clinical evidence
      for potential antitumor activity of CDK4/6 inhibition in other breast cancer
      subtypes is provided. Expert opinion: Future clinical development of CDK4/6
      inhibitors in breast cancer will focus on the following aspects: i) optimization
      of treatment sequencing for patients with advanced disease, ii) early-stage
      disease, iii) other subtypes of breast cancer in rationally chosen therapeutic
      combinations and iv) the identification of predictive biomarkers.

PMID- 29027484
TI  - CYP1A1 expression and organochlorine pesticides level in the etiology of bladder
      cancer in North Indian population.
AB  - Urinary bladder cancer (UBC) is one of the most common malignancies worldwide.
      The etiology of UBC is multifactorial and includes both exogenous and endogenous
      factors. Exogenous risk factors include exposure to heavy metals, aromatic
      amines, and environmental pollutants including pesticides such as organochlorine
      pesticides (OCPs). Environmental factors alone are incapable of directly
      producing DNA damage and may require activation by phase I metabolizing enzymes
      like cytochrome P450 in order to become active carcinogen. The present study is
      designed to study CYP1A1 gene expression, OCP level in cases of UBC, as well as
      to explore the plausible role of gene-environment interaction in the etiology of
      UBC among North Indian population. A total of 60 cases with equal number of
      controls were enrolled under this study, the OCP levels were estimated using gas
      chromatography, CYP1A1 mRNA expression was quantified by real-time quantitative
      polymerase chain reaction, and fold change was calculated using the DeltaDeltaCt
      method. In the present study, the levels of OCP were found to be significantly
      higher with the upregulation of CYP1A1 mRNA expression among UBC cases as
      compared to controls. While putting multiple linear regression, it has been
      observed that there is a significant interaction between the levels of OCPs and
      DeltaCt value of CYP1A1 gene taken into account hematuria episodes as dependent
      variable. The study concludes that when there is predisposition of OCPs and
      upregulation of CYP1A1 gene, then the result will be an increment in hematuria
      episodes which indicates that gene-environment interaction plays a significant
      role in the causation of UBC among North Indian population.

PMID- 29027485
TI  - Concentration-dependent effect of fumonisin B1 on apoptosis in oesophageal cancer
      cells.
AB  - The geographical distribution of oesophageal cancer is linked to the exposure of
      fumonisin B1 (FB1), a mycotoxin produced by fungi that contaminates staple food
      worldwide. Non-genotoxic carcinogens like FB1 disturb homeostasis through
      increased cell proliferation or suppression of apoptosis. This study investigated
      the involvement of FB1 (0-20 MUM) in spindle-shaped N-cadherin (+) CD45 (-)
      osteoblastic (SNO) cell death. Cell viability and death were assessed using the
      MTS and Annexin V-Fluos assays, respectively. Caspase activities were determined
      luminometrically and the comet assay assessed DNA damage. Induction of oxoguanine
      glycosylase 1 (OGG1) was measured using quantitative Polymerase Chain Reaction
      (qPCR), while cleaved poly (ADP-ribose) polymerase 1 (PARP-1) and Bax were
      determined by western blotting. Cell viability and PARP-1 cleavage were not
      affected by 1.25 MUM FB1, but phosphatidylserine externalization, Bax protein
      expression, caspase activity, comet tail length and OGG1 transcripts were
      increased. The reduced cell viability in 10 MUM FB1-treated cells was accompanied
      by corresponding increases in externalized phosphatidylserine, Bax, caspase-3/7
      activity and cleaved PARP-1. The OGG1 transcripts were not significantly
      increased, but comet tails were increased. Bax, caspase-3/7 activities and
      cleaved PARP-1 were inhibited at 20 MUM FB1. In addition, the OGG1 transcript
      levels were decreased ( p < 0.0001) along with comet lengths ( p < 0.0001). This
      study showed that FB1-induced apoptosis in SNO cells may be caspase-dependent or
      caspase-independent; the pathway used depends on the exposure concentration.

PMID- 29027486
TI  - The cancer threshold of toxicological concern (TTC) in relation to foodstuffs and
      pharmaceuticals: A potentially useful concept compromised by a dubious
      derivation.
AB  - The cancer threshold of toxicological concern (TTC) as determined by Kroes et al.
      in 2004 (0.15 ug/day and 1.5 ug/day at risk levels of 1 in 106 or 105,
      respectively) has been uncritically employed as a key metric in multiple
      regulatory guidance documents. There are numerous concerns regarding transparency
      and the highly conservative methodology in relation to its derivation; moreover,
      no formal confirmation has been undertaken by any regulatory body prior to its
      adoption. A recent joint report from the European Food Safety Authority and World
      Health Organization follows this trend, largely replicating previous conclusions
      and downplaying the need for a re-assessment. This view is challenged by Boobis
      et al. who confirm concerns regarding lack of transparency and stress that
      several of the assumptions and approaches used previously have been superseded by
      advances in knowledge; they recommend as a first step construction of a new
      dataset derived from the Carcinogenic Potency Database focusing on mutagenic DNA
      reactive rodent carcinogens and a critical assessment of the relevance and
      reliability of carcinogenicity data. This type of approach is supported with two
      key exceptions: inclusion of data from the ToxTracker assay which provides a
      direct readout of DNA reactivity, and use of appropriate epidemiological data on
      acrylamide (AA) to determine a benchmark for human exposure to a typical DNA
      reactive rodent carcinogen. It is concluded that a robust re-evaluation using an
      appropriate dataset and methodology is urgently needed to ensure the integrity of
      the cancer TTC before it is employed in its present form even more widely.

PMID- 29027488
TI  - Global Health Promotion et la recherche interventionnelle en sante des
      populations.

PMID- 29027489
TI  - Resumes.

PMID- 29027490
TI  - Resumenes.

PMID- 29027487
TI  - Effect of tauroursodeoxycholic acid on PUFA levels and inflammation in an animal
      and cell model of hepatic endoplasmic reticulum stress.
AB  - The aim of this study was to evaluate hepatic polyunsaturated fatty acids (PUFAs)
      and inflammatory response in an animal and cell model of endoplasmic reticulum
      (ER) stress. Rats were divided into control, tunicamycin (TM)-treated, and TM +
      tauroursodeoxycholic acid (TUDCA)-treated groups. Hepatic ER stress was induced
      by TM and the ER stress inhibitor TUDCA was injected 30 min before induction of
      ER stress. Liver THLE-3 cells were treated with TM and TUDCA was administered in
      advance to decrease cytotoxic effects. Necroinflammation was evaluated in liver
      sections, while cell viability was determined using a 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide assay kit. ER stress was confirmed by
      immunofluorescence and Western blot analysis of C/EBP-homologous protein and 78
      kDa glucose-regulated protein. Arachidonic acid (C20:4n-6), dihomo-gamma
      linolenic acid (C20:3n-6), eicosapentaenoic acid (C20:5n-3), and docosahexaenoic
      acid (C22:6n-3) in liver tissue and THLE-3 cells were determined by liquid
      chromatography tandem mass spectrometry (LC-MS/MS). Phospholipase A2 (PLA2),
      cyclooxygenase (COX), and prostaglandin E2 (PGE2) were measured in tissue and
      cell samples. Hepatic ER stress was accomplished by TM and was alleviated by
      TUDCA. TM treatment significantly decreased PUFAs in both liver and THLE-3 cells
      compared to controls. PLA2, COX, and PGE2 levels were significantly increased in
      TM-treated rats and THLE-3 cells compared to controls. TUDCA leads to a partial
      restoration of liver PUFA levels and decreased PLA2, COX, and PGE2. This study
      reports decreased PUFA levels in ER stress and supports the use of omega-3 fatty
      acids in liver diseases demonstrating ER stress.

PMID- 29027492
TI  - Global Health Promotion y la investigacion sobre las intervenciones de salud de
      la poblacion.

PMID- 29027493
TI  - Global health promotion and population health intervention research.

PMID- 29027494
TI  - Discriminating Non-Native Segmental Length Contrasts Under Increased Task
      Demands.
AB  - The present study examines how vulnerable perception of second language prosody
      is to increased task demands. German learners of Japanese, German non-learners
      without exposure to Japanese, and Japanese native listeners were tested in their
      ability to discriminate consonant length contrasts (compared to vowel length
      contrasts that served as a control condition). Memory load was increased by a
      longer inter-stimulus interval (2500 ms compared to 300 ms) and the demand on
      attention control was enhanced through the addition of the acoustic complexity of
      the stimuli (i.e., through a task-irrelevant pitch fall that occurred
      simultaneously with a consonant length contrast). The results showed high
      discrimination abilities, in all groups, when task demands were lowest. With
      increased task demands, only non-native listeners' discrimination abilities
      decreased: non-learners were strongly affected by both increased memory load and
      higher demand on attention control, while learners were only affected by the
      latter. The task-irrelevant acoustic complexity of the stimuli had a stronger
      impact on performance than increased memory load did. The findings suggest that
      second language learners established novel phonological representations but that
      the ability to use them could only be applied in the absence of distracting
      acoustic information. The non-native listeners' reduced sensitivity under
      increased task demands explains why even advanced learners still face
      difficulties in daily listening situations with numerous distractions.

PMID- 29027495
TI  - Monitoring and managing antibiotic resistance in refugee children.
AB  - INTRODUCTION: The past decade the Middle East and Southeastern Europe have
      witnessed an enormous movement of refugees due to the Syrian war and conflicts in
      Asia and Africa. Although carriage of and infections with multi-drug resistant
      (MDR) pathogens in refugees have been reported, pediatric data are scarce. Areas
      covered: MDR bacterial carriage and infections, and MDR-tuberculosis (TB) in
      refugee children from 2010. Expert commentary: High MDR carriage rates in refugee
      children are attributed to high pre-civil war MDR rates, war-damaged
      infrastructure and healthcare systems, and poor hygiene conditions. Currently
      there are no international guidelines about MDR screening in refugee children.
      Given the medical importance of MDRs, challenging therapeutics and risk of
      importation in non/low-endemic countries, we recommend routine screening and
      contact isolation upon hospitalization of refugees. TB, including MDR-TB, is
      highly-endemic in many Asian and African countries, however, current data in
      refugee children are lacking. TB Screening in refugees is widely implemented but
      there is no consensus on methods and target populations. Coordinated TB detection
      and treatment, use of rapid molecular tests and drug-susceptibility testing,
      better access to healthcare, cross border TB care collaboration, and protection
      from deportation while on treatment should be integrated parts of TB control and
      prevention.

PMID- 29027496
TI  - Optimizing usability and signal capture: a proactive risk assessment for the
      implementation of a wireless vital sign monitoring system.
AB  - Wearable vital sign monitors are a promising step towards optimal patient
      surveillance, providing continuous data to allow for early detection and
      treatment of patient deterioration. However, as wearable monitors become more
      widely adopted in healthcare, there is a corresponding need to carefully design
      the implementation of these tools to promote their integration into clinical
      workflows and defend against potential misuse and patient harm. Prior to the roll
      out of these monitors, our multidisciplinary team of clinicians, clinical
      engineers, information technologists and research investigators conducted a
      modified Healthcare Failure Mode and Effect Analysis (HFMEA), a proactive
      evaluation of potential problems which could be encountered in the use of a
      wireless vital signs monitoring system. This evaluation was accomplished by
      focussing on the identification of procedures and actions that would be required
      during the devices' regular usage, as well as the implementation of the system as
      a comprehensive process. Using this method, the team identified challenges that
      would arise throughout the lifecycle of the device and developed recommendations
      to address them. This proactive risk assessment can guide the implementation of
      wearable patient monitors, optimising the use of innovative health information
      technology.

PMID- 29027497
TI  - Comparative evaluation of treatment patterns and healthcare utilization of newly
      diagnosed rheumatoid arthritis patients by anti-cyclic citrullinated peptide
      antibody status.
AB  - BACKGROUND: Anti-cyclic citrullinated peptide (CCP) antibody positivity is an
      established diagnostic factor for severe disease activity and joint damage and a
      prognostic factor for aggressive disease in rheumatoid arthritis (RA). OBJECTIVE:
      To compare RA-related treatment, healthcare utilization, and joint erosion
      between anti-CCP-positive and anti-CCP-negative RA patients. METHODS: Newly
      diagnosed RA patients were identified from the Henry Ford Health System database
      between January 1, 2009 and December 31, 2014; the date of the first RA diagnosis
      within the study period was the index date. Baseline anti-CCP test was used to
      categorize patients as anti-CCP-positive or anti-CCP-negative, and outcomes were
      evaluated in the 6 months post-index. RESULTS: There were 217 anti-CCP-positive
      and 191 anti-CCP-negative RA patients included in the study. A higher proportion
      of anti-CCP-positive patients were initiated on RA treatment than anti-CCP
      negative patients (70.5% vs 23.0%; p < .0001). More anti-CCP-positive patients
      received methotrexate (73.2% vs 56.8%; p = .0374), while more anti-CCP-negative
      patients received hydroxychloroquine (31.8% vs 13.1%; p = .0037) in first-line
      therapy. A higher proportion of anti-CCP-negative patients were tested for
      rheumatoid factor (RF) and erythrocyte sedimentation rate (ESR). Of those tested,
      there were more positive test results in the anti-CCP-positive cohort compared to
      the anti-CCP-negative cohort (RF: 84.4% vs 18.2%, p < .0001; C-reactive protein
      [CRP]: 69.7% vs 48.3%, p = .0008; and ESR: 89.5% vs 53.9%, p < .0001). Outpatient
      utilization predominated, with more anti-CCP-positive patients having any
      outpatient physician office visit (96.3% vs 77.5%, p < .0001) and a higher mean
      number of visits (5.3 vs 2.5, p < .0001) than anti-CCP-negative patients. Among
      anti-CCP-positive (n = 113) and anti-CCP-negative (n = 58) patients with imaging
      results, more anti-CCP-positive patients had joint erosion compared to anti-CCP
      negative patients (18.6% vs 8.6%; p = .0858); however, statistical significance
      was not reached. CONCLUSION: RA patients with positive anti-CCP antibodies had
      higher degrees of inflammation and disease activity as indicated by laboratory
      results, which likely contributed to their higher rates of healthcare
      utilization, joint erosion, and proportions of RA treatment.

PMID- 29027499
TI  - Non-infectious Fever After Acute Spinal Cord Injury in the Intensive Care Unit.
AB  - Objective The aim of the present study is to evaluate the frequency, etiology,
      risk factors and clinical outcomes in acute traumatic SCI patients who develop
      fever and to evaluate the relationship between fever and mortality. Design
      Retrospective data were collected between January 2007 and August 2016 from
      patients diagnosed with persistent fever from SCI cases observed in the ICU.
      Participants Among 5370 intensive care patients, 435 SCI patients were evaluated
      for the presence of fever. A total of 52 patients meeting the criteria were
      evaluated. Outcome measures Fever characteristics were evaluated by dividing the
      patients into two groups: infectious (group-1) and non-infectious (group-2)
      fever. Demographic and clinical data, ICU and hospital stay, and mortality were
      evaluated. Results In the patients with noninfectious fever, mortality was
      significantly higher compared to the group with infectious fever (P < 0.001). Of
      52 acute SCI cases, 25 (48.1%) had neurogenic fever that did not respond to
      treatment in intensive care follow-up, and 22 (88%) of these patients died.
      Maximal fever was 39.10 +/- 0.64  degrees C in Group-1 and 40.22 +/- 1.10 
      degrees  C in Group-2 (P = 0.001). There was a significant difference in the
      duration of ICU stay and hospital stay between the two groups (P = 0.005, P =
      0.001, respectively), while there was no difference in the duration of mechanical
      ventilation between the groups (P = 0.544). Conclusion This study demonstrates
      that patients diagnosed with neurogenic fever following SCI had higher average
      body temperature and higher rates of mortality compared to patients diagnosed
      with infectious fever.

PMID- 29027498
TI  - Relationships between presenteeism and work-related musculoskeletal disorders
      among physical therapists in the Republic of Korea.
AB  - This study investigated the relationship between presenteeism and work-related
      musculoskeletal disorders (WMSDs) among physical therapists (PTs) in the Republic
      of Korea. Questionnaires were given to 600 PTs in the Republic of Korea. General
      and occupational characteristics and the prevalence of presenteeism and
      absenteeism were self-reported on the questionnaire. Stepwise regression analyses
      were used to evaluate the effects of presenteeism and other variables on general
      and occupational characteristics. Of the 490 PTs who responded, 399 (81.4%)
      reported at least one WMSD. There was a low incidence rate of absenteeism, but
      work impairment scores indicate there was a high incidence of presenteeism. In
      the stepwise regression analyses, the incidence of WMSDs was highest in cases of
      presenteeism. The results of this study demonstrate that there is a high
      incidence rate of WMSDs in Republic of Korean PTs, that WMSDs are related to
      presenteeism and that PTs demonstrate high presenteeism and low absenteeism.

PMID- 29027500
TI  - Novel steroidal saponins from Dioscorea esculenta (Togedokoro).
AB  - Fifteen steroidal saponins 1-15, which include 4 furostanol glycosides 1-3 and
      15, and 11 spirostanol glycosides 4-14, were isolated from the tubers and leaves
      of lesser yam (Dioscorea esculenta, Togedokoro). Their structures were identified
      by nuclear magnetic resonance and liquid chromatography mass spectroscopy. Four
      steroidal saponins 9, 11, 14, and 15 were found to be novel compounds.

PMID- 29027501
TI  - Anticancer activity of new imidazole derivative of 1R,2R-diaminocyclohexane
      palladium and platinum complexes as DNA fluorescent probes.
AB  - The aim of this study was synthesis of two new water-soluble fluorescent
      palladium and platinum complexes with formulas of [Pt(DACH)(FIP)](NO3)2 and
      [Pd(DACH)(FIP)](NO3)2, respectively, where FIP is 2-(furan-2-yl)-1H-imidazo[4,5
      f][1,10] phenanthroline and DACH is 1R,2R-diaminocyclohexane. Fluorescence
      spectroscopy, circular dichroism (CD), thermal denaturation measurement, ionic
      strength, and kinetic study displayed groove binding of Pt complex on DNA, while
      due to binding of Pd complex, B form of DNA convert to Z form. Due to
      electrostatic interaction of Pd complex with DNA, the DNA form is converted and
      it provides enough space for Pd complex to insert between base stacking of DNA.
      UV-vis study shows two complexes could denature the DNA at low concentrations in
      exothermic process and Pt complex is more active than Pd complex. Finally, the
      anticancer and growth inhibitory activities of synthesized complexes were
      investigated against human colon cancer cell line HCT116 after incubation time of
      24 h using MTT assay and higher activity was observed for the platinum complex.
      Interaction of the two metal derivative complexes was studied by molecular
      docking and molecular dynamics simulation. The results showed that Pt complexes
      have higher negative docking energy and higher tendency for interaction with DNA,
      and exert more structural change on DNA.

PMID- 29027502
TI  - Development and validation of the self-administered Falun health instrument
      (SAFHI) using data from health promoted workplaces in Sweden.
AB  - AIM: The aim of this study was to develop and to validate the self-administered
      Falun health instrument. An additional aim was to test its applicability in
      measuring people's lifestyles linked to health. METHODS: In 2002, an instrument
      was constructed containing questions regarding the hazardous use of alcohol,
      tobacco, unhealthy diets and insufficient physical activity. A pilot study using
      the instrument was assessed between 2002 and 2006. In Sweden, it was further
      expanded and tested during the years 2004-2014 among a total of 1295 people.
      RESULTS: Face validity was evaluated among colleagues and experts for clarity and
      completeness resulting in minor adjustments of some questions. With the test
      retest method, the self-administered Falun health questionnaire showed a positive
      and high reproducibility and high compliance. Cronbach's alpha showed a high
      level of consistency (average 0.86). Factor analysis demonstrated the choice of
      questions correlated highly to the measured lifestyle. CONCLUSIONS: This study
      showed that the self-administered Falun health questionnaire is a valid and
      reliable instrument, useful for detecting individuals at risk of developing
      diseases that are related to individual choice of lifestyle.

PMID- 29027503
TI  - Antioxidant effect of aromatic volatiles emitted by Lavandula dentata, Mentha
      spicata, and M. piperita on mouse subjected to low oxygen condition.
AB  - This study aims to investigate the antioxidant effect of aromatic volatiles of
      three common aromatic plants, Lavandula dentata, Mentha spicata, and M. piperita.
      In this study, kunming mice subjected to low oxygen condition were treated with
      the volatiles emitted from these aromatic plants through inhalation
      administration. Then the blood cell counts, and the activities and gene
      expressions of antioxidant enzymes in different tissues were tested. The results
      showed that low oxygen increased the counts of red blood cells, white blood
      cells, and blood platelets of mice, and aromatic volatiles decreased their
      counts. Exposure to aromatic volatiles resulted in decreases in the malonaldehyde
      contents, and increases in the activities and gene expressions of superoxide
      dismutase, glutathione peroxidase, and catalase in different tissues under low
      oxygen. In addition, as the main component of aromatic volatiles, eucalyptol was
      the potential source that imparted positive antioxidant effect.

PMID- 29027504
TI  - Pharmacokinetic considerations for use of artemisinin-based combination therapies
      against falciparum malaria in different ethnic populations.
AB  - INTRODUCTION: Artemisinin-based combination therapy (ACT) is used extensively as
      first-line treatment for uncomplicated falciparum malaria. There has been no
      rigorous assessment of the potential for racial/ethnic differences in the
      pharmacokinetic properties of ACTs that might influence their efficacy. Areas
      covered: A comprehensive literature search was performed that identified 72
      publications in which the geographical origin of the patients could be
      ascertained and the key pharmacokinetic parameters maximum drug concentration
      (Cmax), area under the plasma concentration-time curve (AUC) and elimination half
      life (t1/2beta) were available for one or more of the five WHO-recommended ACTs
      (artemether-lumefantrine, artesunate-amodiaquine, artesunate-mefloquine,
      dihydroartemisinin-piperaquine and artesunate-sulfadoxine-pyrimethamine).
      Comparisons of each of the three pharmacokinetic parameters of interest were made
      by drug (artemisinin derivative and long half-life partner), race/ethnicity
      (African, Asian, Caucasian, Melanesian, South American) and patient categories
      based on age and pregnancy status. Expert opinion: The review identified no
      evidence of a clinically significant influence of race/ethnicity on the
      pharmacokinetic properties of the nine component drugs in the five ACTs currently
      recommended by WHO for first-line treatment of uncomplicated falciparum malaria.
      This provides reassurance for health workers in malaria-endemic regions that ACTs
      can be given in recommended doses with the expectation of adequate blood
      concentrations regardless of race/ethnicity.

PMID- 29027505
TI  - Impact of non-uniform correlation structure on sample size and power in multiple
      period cluster randomised trials.
AB  - Stepped wedge and cluster randomised crossover trials are examples of cluster
      randomised designs conducted over multiple time periods that are being used with
      increasing frequency in health research. Recent systematic reviews of both of
      these designs indicate that the within-cluster correlation is typically taken
      account of in the analysis of data using a random intercept mixed model, implying
      a constant correlation between any two individuals in the same cluster no matter
      how far apart in time they are measured: within-period and between-period intra
      cluster correlations are assumed to be identical. Recently proposed extensions
      allow the within- and between-period intra-cluster correlations to differ,
      although these methods require that all between-period intra-cluster correlations
      are identical, which may not be appropriate in all situations. Motivated by a
      proposed intensive care cluster randomised trial, we propose an alternative
      correlation structure for repeated cross-sectional multiple-period cluster
      randomised trials in which the between-period intra-cluster correlation is
      allowed to decay depending on the distance between measurements. We present
      results for the variance of treatment effect estimators for varying amounts of
      decay, investigating the consequences of the variation in decay on sample size
      planning for stepped wedge, cluster crossover and multiple-period parallel-arm
      cluster randomised trials. We also investigate the impact of assuming constant
      between-period intra-cluster correlations instead of decaying between-period
      intra-cluster correlations. Our results indicate that in certain design
      configurations, including the one corresponding to the proposed trial, a
      correlation decay can have an important impact on variances of treatment effect
      estimators, and hence on sample size and power. An R Shiny app allows readers to
      interactively explore the impact of correlation decay.

PMID- 29027506
TI  - Coprolalia in aphasic patients with stroke: a longitudinal observation from the
      BLAS2T database.
AB  - The BLAS2T (bilingual aphasia in stroke-study team) initiative has been a multi
      center attempt to investigate longitudinal changes in language function in a
      cohort of stroke subjects. This report discusses linguistic performance in four
      cases from the BLAS2T database who demonstrated coprolalia as an irresistible
      urge to say obscene words.  Coprolalia was found to partly resolve in a 30-day
      follow-up in three cases. Recognition of coprolalia and language recovery
      patterns in bilingual aphasic patients with stroke would potentially lead to
      their even better individualized care and neurolinguistic/cognitive
      rehabilitation.

PMID- 29027508
TI  - Practice-Based Small Group Learning (PBSGL) in Scotland - a survey of registered
      pharmacy staff and general practice nurses.
AB  - INTRODUCTION: Practice-based small group learning (PBSGL) has grown in primary
      healthcare in Scotland, and is used regularly by 2244 GPs and GP specialist
      trainees. The programme has been available to general practice nurses (GPNs) and
      pharmacy staff since uni-professional and inter-professional pilot studies were
      considered successful. Growth has been slower compared to GPs uptake but has now
      reached significant levels. It seemed timely to evaluate the use of the programme
      by these professions. METHOD: A questionnaire previously used by GPs was adapted.
      It consisted of 16 questions and two free text questions asking respondents what
      had motivated them to join PBSGL, and what encouraged them to maintain
      membership. The questionnaire was converted into an electronic format and emailed
      to pharmacy and GPNs in Scotland who were PBSGL members. RESULTS: A range of
      pharmacy staff and GPNs were involved in PBSGL and the mean number of modules
      studied by pharmacy staff was 3.93 and 4.48 by GPNs in the last year. A high
      percentage were likely or very likely to continue with membership (pharmacy staff
      - 95.6%, GPNs - 90.1%). The dominant reasons to join and stay in the programme
      related to learning issues: meeting learning needs, learning from peers and
      professional socialisation.

PMID- 29027507
TI  - Development of an mHealth trauma registry in the Middle East using an
      implementation science framework.
AB  - BACKGROUND: Trauma registries (TRs) play a vital role in the assessment of trauma
      care, but are often underutilized in countries with a high burden of injuries.
      OBJECTIVES: We investigated whether information and communications technology
      (ICT) such as mobile health (mHealth) could enable the design of a tablet-based
      application for healthcare professionals. This would be used to inform trauma
      care and acquire surveillance data for injury control and prevention in Oman.
      This paper focuses on documenting the implementation process in a healthcare
      setting. METHODS: The study was conducted using an ICT implementation framework
      consisting of multistep assessment, development and pilot testing of an
      electronic tablet-based TR. The pilot study was conducted at two large hospitals
      in Oman, followed by detailed evaluation of the process, system and impact of
      implementation. RESULTS: The registry was designed to provide comprehensive
      information on each trauma case from the location of injury until hospital
      discharge, with variables organized to cover 11 domains of demographic and
      clinical information. The pilot study demonstrated that the registry was user
      friendly and reliable, and the implementation framework was useful in planning
      for the Omani hospital setting. Data collection by trained and dedicated nurses
      proved to be more feasible, efficient and reliable than real-time data entry by
      care providers. CONCLUSIONS: The initial results show the promising potential of
      a user-friendly, comprehensive electronic TR through the use of mHealth tools.
      The pilot test in two hospitals indicates that the registry can be used to create
      a multicenter trauma database.

PMID- 29027509
TI  - Multiply adjusted comparisons: A meta-analysis method to compare single-arm
      clinical-trial data to literature results regarding a competitor.
AB  - Prospective randomized controlled trials are difficult to obtain if a promising
      new therapy has to be tested against seemingly obsolete alternatives. One method
      to address this problem is to compare the results of (multicentre) trials to
      literature results. However, previous treatment-era changes and population
      dependent results complicate objective comparisons. The presented approach
      describes a method to objectify such comparisons in cases in which individual raw
      data regarding a new therapy have to be compared to summary results regarding a
      conventional alternative published in the literature. The chosen example is the
      introduction of bovine neck veins as a substitute for dysfunctional human
      pulmonary valves, and the conventional therapeutic alternative is pulmonary
      artery homografts. Literature research, subgroup identification, filtering,
      endpoint remodelling, weighting and, if necessary, confidence-limit calculation
      yield adjusted comparisons. These individual comparisons are then aggregated,
      first by article and then over several articles (similar to meta-analyses),
      resulting in a differentiated panel of answers (Multiply Adjusted Comparisons).
      In situations in which extensive raw data regarding a new therapeutic alternative
      but no randomized controlled trials and no raw data from previous studies using
      the conventional therapeutic alternative are available, the proposed method
      identifies the best evidence and is by far superior to unadjusted direct
      comparisons or gut feelings.

PMID- 29027510
TI  - Comparing the efficacy of topical hydroquinone 2% versus intradermal tranexamic
      acid microinjections in treating melasma: a split-face controlled trial.
AB  - INTRODUCTION: Melasma is a benign, acquired and chronic hypermelanosis. Topical
      hydroquinone (HQ) is a conventional choice to treat melasma. Tranexamic acid (TA)
      is a relatively new brightening agent that interferes with keratinocyte
      melanocyte interactions. The aim of the present study was to compare the efficacy
      and safety of TA intradermal injections with HQ in treating melasma. MATERIALS
      AND METHODS: In this split-face controlled trial, 37 patients were randomized to
      receive three monthly sessions of TA intradermal injections either on the right
      or the left side of their face and topical HQ once a night for three months on
      the other side. Melanin and erythema were measured for each side of the face at
      the baseline and at the end of each month. RESULTS: A reduction in melanin value
      was observed for TA and HQ separately (p value <.001). Monthly TA injection was
      better than daily HQ in reducing the melanin value during the first four weeks (p
      value =.013); but after 20 weeks, the overall changes was not different between
      the two groups (p value =.17). CONCLUSION: Monthly TA intradermal injections can
      be an effective treatment for melasma. Further studies are required to support
      our results.

PMID- 29027512
TI  - Challenges associated with missing data in electronic health records: A case
      study of a risk prediction model for diabetes using data from Slovenian primary
      care.
AB  - The increasing availability of data stored in electronic health records brings
      substantial opportunities for advancing patient care and population health. This
      is, however, fundamentally dependant on the completeness and quality of data in
      these electronic health records. We sought to use electronic health record data
      to populate a risk prediction model for identifying patients with undiagnosed
      type 2 diabetes mellitus. We, however, found substantial (up to 90%) amounts of
      missing data in some healthcare centres. Attempts at imputing for these missing
      data or using reduced dataset by removing incomplete records resulted in a major
      deterioration in the performance of the prediction model. This case study
      illustrates the substantial wasted opportunities resulting from incomplete
      records by simulation of missing and incomplete records in predictive modelling
      process. Government and professional bodies need to prioritise efforts to address
      these data shortcomings in order to ensure that electronic health record data are
      maximally exploited for patient and population benefit.

PMID- 29027513
TI  - [Sharing patient information with neighbourhood social support teams; a legal
      perspective].
AB  - The beginning of 2015 saw the transition of responsibility for social care, youth
      care and participation of vulnerable groups in the Netherlands from the
      government to local authorities. A large majority of municipalities chose to work
      with neighbourhood social support teams. Their main purpose is to offer
      integrated care to citizens. Integrated care requires information-sharing between
      organisations and (healthcare) professionals. Are medical practitioners
      authorized to share patient information with neighbourhood social support teams?
      Legal analysis shows that a medical practitioner may play one of the following
      three roles when sharing information with such teams: the role of referrer, the
      role of expert or the role of informant. Each role comes with specific rules to
      protect patient confidentiality and safeguard patient privacy. Being aware of
      one's role and acting accordingly may positively influence integrated care.

PMID- 29027511
TI  - Evaluation of a Frequency-Lowering Algorithm for Adults With High-Frequency
      Hearing Loss.
AB  - The objective was to determine the effects of a frequency-lowering algorithm
      (frequency composition, Fcomp) on consonant identification, word-final /s, z/
      detection, the intelligibility of sentences in noise, and subjective benefit, for
      people with high-frequency hearing loss, including people with dead regions (DRs)
      in the cochlea. A single-blind randomized crossover design was used. Performance
      with Bernafon Acriva 9 hearing aids was compared with Fcomp off and Fcomp on.
      Participants wore the hearing aids in each condition in a counterbalanced order.
      Data were collected after at least 8 weeks of experience with a condition.
      Outcome measures were audibility, scores from the speech perception tests, and
      scores from a questionnaire comparing self-perceived hearing ability with Fcomp
      off and Fcomp on. Ten adults with mild to severe high-frequency hearing loss
      (seven with extensive DRs, one with patchy or restricted DRs, and two with no DR)
      were tested. Fcomp improved the audibility of high-frequency sounds for 6 out of
      10 participants. There was no overall effect of Fcomp on consonant
      identification, but the pattern of consonant confusions varied across conditions
      and participants. For word-final /s, z/ detection, performance was significantly
      better with Fcomp on than with Fcomp off. Questionnaire scores showed no
      differences between conditions. In summary, Fcomp improved word-final /s, z/
      detection. No benefit was found for the other measures.

PMID- 29027514
TI  - [A male with intra-abdominal nodules on a CT scan].
AB  - A 38-year-old male with a history of laparoscopic cholecystectomy and
      successfully treated Hodgkin lymphoma had a follow-up CT-scan which showed four
      nodular densities behind the bladder. Additional investigations demonstrated
      spilled gallstones instead of a relapse of Hodgkin lymphoma. Spillage of
      gallstones is relatively common and may mimic malignant diseases.

PMID- 29027515
TI  - [A boy with a white striped knee on a radiograph].
AB  - A 10-year-old boy presented at the radiology department with pain in the right
      knee. Radiographs of the knee revealed dens metaphyseal bands and subchondral
      epiphyseal sclerosis as a result of periodic bisphosphonate administration for
      the treatment of Legg-Calve-Perthes disease three years ago.

PMID- 29027516
TI  - [Chronic thromboembolic pulmonary hypertension: recognition, diagnosis and
      treatment].
AB  - - Chronic thromboembolic pulmonary hypertension (CTEPH), characterised by
      pulmonary hypertension and persistent perfusion defects despite adequate
      anticoagulation, causes significant morbidity and mortality.- Persistent dyspnoea
      after acute pulmonary embolism is frequent and an indication for additional
      diagnostics. Only a minority of these patients develop CTEPH.- Echocardiography
      and perfusion scintigraphy are the cornerstone of diagnostics when suspecting
      CTEPH. Right-heart catheterisation and pulmonary angiography should confirm the
      diagnosis.- The diagnostic phase is preferably carried out in an expert centre in
      order to optimise the diagnosis and choose the optimal treatment for each
      individual patient.- Treatment of patients with CTEPH is a multidisciplinary team
      effort.- Pulmonary endarterectomy is the only potentially curative treatment;
      perioperative mortality is less than 5% in experienced centres. Inoperable
      patients can be treated with medication that specifically targets pulmonary
      arterial hypertension, but a survival benefit has not yet been shown for this
      medication.- Balloon pulmonary angioplasty has recently become available in the
      Netherlands as a treatment option, but the exact role of this new technique in
      the treatment of patients with CTEPH still needs to be investigated.

PMID- 29027517
TI  - [Unexpected symptoms of monoclonal gammopathy].
AB  - Monoclonal gammopathy of undetermined significance (MGUS) is a common
      haematological disorder characterized by the presence of a monoclonal protein (M
      protein). MGUS is considered an asymptomatic 'innocent' pre-malignant precursor
      condition of - mostly - multiple myeloma, without indication for treatment. We
      present three cases illustrating that MGUS can lead to serious problems. The
      first patient, a 51-year-old female, presented with polyneuropathy due to anti
      MAG antibodies related to IgM MGUS. The second patient, a 37-year-old female,
      presented with proteinuria due to immunotactoid glomerulopathy caused by renal
      monoclonal IgG deposition associated with MGUS. The third patient, a 55-year-old
      female, presented with severe bleeding caused by an aspecific inhibitor of the
      coagulation cascade as part of IgG MGUS. In conclusion, in addition to the risk
      of progression to an overt haematological malignancy, MGUS can lead to severe
      symptoms and significant organ damage by auto-antibody activity or pathological
      accumulation in tissues of its toxic M-protein.

PMID- 29027518
TI  - [Influenza vaccination of patients with solid tumours during chemotherapy:
      efficacy and safety].
AB  - - Adult patients with solid tumours receiving chemotherapy have reduced immunity
      against infections and are at increased risk of influenza infection and its
      complications. However, many of said patients are not vaccinated for influenza.-
      Limited observational research in this patient group has given some indication of
      the protective effects of the influenza vaccine on clinical outcome measures.-
      Serological studies have shown that the antibody response following influenza
      vaccination is often less pronounced in patients with solid tumours compared to
      healthy individuals. Nonetheless, in most cases a timely protective antibody
      response can be achieved.- The inactivated influenza vaccine is safe in
      immunosuppressed patients, irrespective of the moment at which it is
      administered. Side-effects are similar, both in nature and number, to those seen
      in healthy individuals.- Influenza vaccination can be offered to all adult
      patients with solid tumours, preferably before chemotherapy is commenced.
      Vaccination during chemotherapy, however, usually also generates sufficient
      vaccination response and can reduce the risk of influenza-related complications.
      Therefore, chemotherapy should not preclude patients from being administered the
      influenza vaccine.

PMID- 29027519
TI  - Transmission in the Origins of Bacterial Diversity, From Ecotypes to Phyla.
AB  - Any two lineages, no matter how distant they are now, began their divergence as
      one population splitting into two lineages that could coexist indefinitely. The
      rate of origin of higher-level taxa is therefore the product of the rate of
      speciation times the probability that two new species coexist long enough to
      reach a particular level of divergence. Here I have explored these two parameters
      of disparification in bacteria. Owing to low recombination rates, sexual
      isolation is not a necessary milestone of bacterial speciation. Rather,
      irreversible and indefinite divergence begins with ecological diversification,
      that is, transmission of a bacterial lineage to a new ecological niche, possibly
      to a new microhabitat but at least to new resources. Several algorithms use
      sequence data from a taxon of focus to identify phylogenetic groups likely to
      bear the dynamic properties of species. Identifying these newly divergent
      lineages allows us to characterize the genetic bases of speciation, as well as
      the ecological dimensions upon which new species diverge. Speciation appears to
      be least frequent when a given lineage has few new resources it can adopt, as
      exemplified by photoautotrophs, C1 heterotrophs, and obligately intracellular
      pathogens; speciation is likely most rapid for generalist heterotrophs. The
      genetic basis of ecological divergence may determine whether ecological
      divergence is irreversible and whether lineages will diverge indefinitely into
      the future. Long-term coexistence is most likely when newly divergent lineages
      utilize at least some resources not shared with the other and when the resources
      themselves will coexist into the remote future.

PMID- 29027521
TI  - Wing and body kinematics measurement and force analyses of landing in fruit
      flies.
AB  - In this paper, we analyzed the body and wing kinematics and mechanics in fruit
      flies' landings on a vertical pole. By high-speed video techniques and CFD
      method, we exhibited the detailed process of landing as follows. A fruit fly
      first decelerates and enters a near-hover state approximately 25 mm away from the
      vertical pole, then starts approaching the pole in acceleration till one of its
      front-legs touches the pole (touchdown). Just before touchdown, the fly's
      acceleration is around 6 ms-2; at touchdown, it experiences an almost instant
      deceleration of several g (gravitational acceleration), approximately all of
      which results from the leg force. After touchdown, the fly's acceleration
      fluctuates about zero, and the acceleration is also mainly due to the leg force;
      meanwhile the aerodynamic force decreases to zero and the fly's weight is
      gradually shifted to legs. In this period, the fly's legs act as a compression
      spring, and the fly can be regarded as a legs-body oscillator. In conclusion,
      during landing, the fly keeps accelerating towards the target and 'impinges' on
      the target on its legs, and the leg force, not aerodynamic force, is used to stop
      the insect's motion.

PMID- 29027520
TI  - Further evidence associating IgG1, but not IgG2, with susceptibility to canine
      visceral leishmaniasis caused by Leishmania (L.) infantum chagasi-infection.
AB  - We present here a cross-sectional study analyzing the IgG1 and IgG2 immune
      responses to natural canine Leishmania (L.) infantum chagasi-infection and their
      relationships with delayed-type hypersensitivity (DTH) in 50 mongrel dogs with
      previous positive serodiagnoses (IFAT-IgG) (56% with subclinical status [=
      apparently healthy] and 44% clinically sick), living in endemic areas for
      visceral leishmaniasis in the Brazilian Amazon. IgG1 and IgG2 responses were
      measured using commercial polyclonal antibodies in ELISA, while DTH was elicited
      by intradermal skin test using cultured promastigotes L. (L.) i. chagasi-antigen.
      Data analyses used Chi-square and Pearson's r coefficient (95% confidence
      interval). Regarding DTH and the clinical statuses of dogs, it was noted that
      100% of the animals showing positive DTH (n = 8) were from the subclinical group,
      while 100% showing negative DTH were from the clinically sick group; higher IgG2
      than IgG1 responses were observed in both clinical groups. However, when this
      comparison was made between the subclinical and sick groups, higher IgG1
      responses were noted in the dogs from the sick rather than the subclinical group,
      while no differences were noted between the IgG2 responses in the dogs from both
      clinical groups. Additionally, we found lower IgG1 responses in dogs from the
      subclinical group showing positive DTH than in the dogs from the subclinical or
      sick groups with negative DTH; no differences were found between the IgG2
      responses of these two clinical groups. These findings suggest that the IgG1, but
      not the IgG2, response is associated with susceptibility to canine visceral
      leishmaniasis (CVL).

PMID- 29027522
TI  - [Morphochemical changes in the substantia nigra cellular structures in
      Parkinson's disease].
AB  - AIM: to clarify the features of morphochemical changes in the substantia nigra
      cellular structures in Parkinson's disease. MATERIAL AND METHODS: The structural
      characteristics of the substantia nigra were studied microscopically and
      quantified using computer morphometric methods at brain autopsies of individuals
      with Parkinson's disease who had died from intercurrent diseases and those who
      had no evidence of neurological disorders in their history (a control group).
      RESULTS: This investigation could clarify the features of morphochemical changes
      in both the neural network structures and the glial populations of the substantia
      nigra in Parkinson's disease. The number of neurons containing tyrosine
      hydroxylase (a marker of dopamine neurons) in the compact part of the substantia
      nigra (a ventral region) was smaller and the density distribution of Lewy bodies
      was higher in the patients with Parkinson's disease than in the control group.
      The accumulation of iron (II) compounds in the cellular elements and neuropile
      and the increased expression of glial fibrillary acidic protein in Parkinson's
      disease were more pronounced than those in the controls. CONCLUSION: Postmortem
      diagnosis in Parkinson's disease should be based on a full description of a set
      of neuronal and glial morphochemical and structural changes in the substantia
      nigra rather than on the identification of cellular markers for the
      neurodegenerative process.

PMID- 29027523
TI  - [Role of tenascin S in triple-negative breast cancer].
AB  - AIM: to establish a relationship between the main markers tumor stem cells
      (TSCs), CD44, and CD24, the level of tenascin C production, and chemoresistance
      in triple-negative breast cancer (BC). SUBJECTS AND METHODS: Thirty biopsy
      specimens from triple-negative BC patients who had conventionally received
      preoperative chemotherapy followed by surgery were selected in the investigation.
      All the selected patients were conventionally assigned to neoadjuvant
      polychemotherapy (PCT) with paclitaxel and carboplatin. The surgical specimens
      were analyzed in relation to the degree of a tumor morphological response to PCT.
      The magnitude of the health-promoting effect of neoadjuvant therapy was evaluated
      according to the residual cancer burden (RCB) system using an on-line calculator;
      RCB was categorized into classes (from RCB-0 to RCB-III). The markers CD44, SD24,
      and tenascin C were identified by the standard immunoperoxidase method in the
      primary biopsies. RESULTS: Varying morphological responses of triple-negative
      breast cancer to PCT were revealed, which showed resistance in 60% of the cases.
      The chemoresistance found in most (87%) cases coincided with the identification
      of the CD44+/CD24low/- profile. The detection of the higher production of the
      extracellular matrix tenascin C participating in the formation of the TSC niche
      fully combined with the CD44+/CD24low/- phenotype; while the maximum response to
      tenascin C was noted in the cases differing in not only a lack of responses to
      PCTs, but also in the most aggressive course in conjunction with metastatic
      disease. CONCLUSION: Immunohistochemical analysis shows that the unique
      association between the CD44+/CD24low/- phenotype and the pronounced production
      of tenascin C may have a prognostic potential, prospectively indicating the
      inefficiency of neoadjuvant PCT, in particular that with platinum derivatives,
      which is used for the standard treatment of triple-negative BC. Taking into
      account the role of tenascin C in invasion, metastasis, and chemoresistance, it
      per se may be considered as a promising target for the targeted and/or combined
      therapy of triple-negative BC.

PMID- 29027524
TI  - [The morphological and immunohistochemical characteristics of stratified mucin
      producing intraepithelial lesion].
AB  - : Stratified mucin-producing intraepithelial lesion (SMILE) is a rare
      premalignant cervical lesion that combines the structural features of cervical
      intraepithelial neoplasia (CIN) and endocervical adenocarcinoma in situ (AIS).
      AIM: to analyze archival materials for the detection of SMILE and its subsequent
      morphological and immunohistochemical characterization. MATERIAL AND METHODS:
      Cervical cone specimens from 53 women with histologically verified CIN3 were
      examined. The diagnosis of SMILE was based on the positive mucicarmine staining
      and weak focal expression of p63. The samples containing SMILE were further
      immunohistochemically examined using the biomarkers P16, Ki-67, Oct4, CD117,
      CD34, p53, EMA, and CK15. SMILE was detected in 2 of the 53 patients and
      concurrent with CIN3 in both cases. SMILE was characterized by the stratified
      arrangement of atypical cells containing mucin, the positive mucicarmine staining
      of the entire layer of the atypical epithelium, weak focal p63 expression, high
      Ki-67 expression, and diffuse r16Ink4a staining. Both SMILE samples showed weak
      diffuse p53 expression in the presence of single cells with the pronounced
      nuclear staining pattern for p53 in one female patient. Weak focal CK15
      expression was visualized in SMILE. The expression of the stem cell markers Oct4
      and CD117 and the angiogenic marker CD34 was absent in the examined cervical
      epithelial preparations. The diffuse and intense expression of the marker EMA,
      which was not different from that in the endocervical and stratified squamous
      epithelium, and CIN3 was established in SMILE. RESULTS: The findings suggest that
      SMILE is morphologically and immunohistochemically similar to CIN3. In this
      investigation, these abnormalities differed only in the mucicarmine staining and
      expression of p63. This may be indicative of the underdiagnosis of SMILE,
      attendant SIN3 in the routine practice of a clinical pathologist, as the
      diagnosis of CIN3 is primarily based on the results of assessment of only the
      preparations stained with hematoxylin and eosin; the expression of p16 and Ki-67
      is evaluated in some cases, which fails to differentiate SMILE and CIN3 in a
      number of preparations. CONCLUSION: The diagnosis of SMILE can be made only by
      immunohistochemical examination.

PMID- 29027525
TI  - [Gigantic aneurysm of the coronary artery].
AB  - The paper describes a clinical case of gigantic aneurysm of one of the coronary
      arteries. It considers the morphological and immunohistochemical characteristics
      of the wall of the blood vessel with the detected signs of coronaritis. The
      authors have determined that Kawasaki disease could be retrospectively diagnosed
      in early childhood.

PMID- 29027526
TI  - [Investigation of the structure of a functionally intact xenopericardial
      bioconduit after long-term implantation].
AB  - AIM: to investigate the cellular composition of a functionally intact
      xenopericardial valve in a recipient with acquired mitral defect after long-term
      implantation. MATERIAL AND METHODS: A Uniline bioconduit (BC) ('Neocor',
      Kemerovo) removed from the heart in the mitral position at 7.2 years after
      implantation was investigated. Heart valve leaflets were fixed in a buffered 4%
      paraformaldehyde solution and imbedded in paraffin or epoxy resin. Slices made
      from the paraffin samples were stained with hematoxylin and eosin or underwent
      immunohistochemical (IHC) examination for typing endothelial cells, smooth muscle
      cells, macrophages, fibroblasts, and T and B lymphocytes. The epoxy resin
      embedded samples were examined using light and scanning electron microscopy
      according to the original procedure. For this, the samples were ground and
      polished, then stained with toluidine blue and basic fuchsin or contrasted with
      uranyl acetate and lead citrate. RESULTS: Different cell types were found in the
      outer layers of heart valve leaflets. IHC showed that endothelial cells,
      macrophages, smooth muscle cells, and fibroblasts were present in the samples. A
      relationship was found between the degree of degenerative changes in the BC
      surface and the magnitude of cellular infiltration in xenotissue. This paper
      debates whether impaired integrity of the surface leaflet layers plays a trigger
      role in structural dysfunctions of the implanted valves and whether BC
      endothelialization has a protective effect, which can considerably reduce the
      immunogenicity of xenotussie and prevent the penetration of recipient cells.
      CONCLUSION: The paper shows that it is expedient to modify the surface of the
      heart valve leaflets in order to create favorable conditions for the attachment
      and function of endothelial progenitor cells.

PMID- 29027527
TI  - [Laryngeal paraganglioma].
AB  - The paper describes a clinical case of laryngeal paraganglioma, a rare tumor. It
      provides the detailed characteristics of current diagnostic techniques.

PMID- 29027528
TI  - [Nasal glial heterotopia: Clinical and morphological characteristics].
AB  - The paper describes a case of nasal glial heterotopia in a 10-month-old girl with
      a mixed (intranasal and subcutaneous) localization, which is accompanied by the
      divergence of the nasal bones. Histological examination supplemented by
      immunohistochemical reactions with antibodies to vimentin, S100 protein, neuron
      specific enolase, as well as Ki-67 and smooth muscle actin confirmed the neural
      nature of the tumor. Fields of mature astrocytic glia including individual cells
      with neuronal differentiation were found among the fibrous and fibrovascular
      tissues. The paper provides a brief overview of the discussed pathology.

PMID- 29027529
TI  - [Twin pregnancy with complete hydatidiform mole].
AB  - The paper describes a case of twin pregnancy with complete hydatidiform mole
      (CHM). According to the data available in the literature, the concurrence of CHM
      with a normal placenta and a viable fetus occurs in 1 per 20,000-100,000
      pregnancies, requires a differential diagnosis with partial hydatidiform mole and
      placental mesenchymal dysplasia, and is characterized by a high rate of
      complications. In this concurrence, the frequency of persistent trophoblastic
      disease is as high as 50%. In this case, the pregnancy ended in a spontaneous
      abortion at 16-17 weeks of pregnancy. A morphological examination determined the
      fetus without congenital malformations with normal placental weight and structure
      and the adjacent intact placental tissue with the macro- and microscopic signs of
      CHM. The diagnosis was confirmed by the lack of r57 expression in the villous
      trophoblast and stroma in the tissue of the hydatidiform mole. The patient was
      diagnosed with persistent trophoblastic disease at 2 months after the abortion.

PMID- 29027531
TI  - [Costal cartilage structural and functional changes in children with a funnel or
      keeled chest].
AB  - Congenital chest wall deformities (CCWDs) in children are severe diseases leading
      to cosmetic defects and diseases of the respiratory and cardiovascular systems.
      The most common of these deformities are funnel-shaped (pectus excavatum, FD) and
      keeled (pectus carinatum, KD) ones. The pathogenesis of CCWDs and the role of
      costal cartilage structural and functional changes in their pathogenesis have now
      been not well studied, which makes it difficult to elaborate pathogenetic
      approaches to correcting these diseases. Analysis of the literature has shown
      that structural and functional changes occur in the matrix and chondrocytes from
      the costal cartilage in FD. Similar costal cartilage changes are observed in KD.
      It is still unknown exactly which pathological processes are present in the
      costal cartilage and how they result in the development of one or other type of
      CCWDs. The role of amianthoid transformation (AT) of costal cartilages in these
      processes is also unknown. It is not improbable that it is AT drastically
      changing the native cartilage matrix, which is one of the key mechanisms leading
      to changes in its properties and to the subsequent development of FD or KD.

PMID- 29027530
TI  - [Automatic morphometric analysis as a method for determining the level of
      extracellular matrix components and for quantifying nuclear antigens].
AB  - Automated image analysis methods are highly important for biotechnology research.
      The authors developed and tested a program for the morphometric analysis of
      photomicrographs of the sections processed using the standard immunohistochemical
      examination protocols. The color deconvolution method used in the algorithm was
      proven to be effective in mapping the distribution of DAB chromogen in the sample
      containing multiple dyes. The experiment demonstrated that the level of
      extracellular matrix proteins could be comparatively quantified in different
      groups of samples. The effective methods for the quantitative analysis of the Ki
      67 labelling index were also tested using the same algorithms. The developed
      program was published under free GPL 3.0.

PMID- 29027532
TI  - [Mikhail Matveevich Rudnev is one of the founders of Russian pathological anatomy
      (On the occasion of the 180th anniversary of his birth)].

PMID- 29027533
TI  - Factors associated with circulating concentrations of irisin in the general
      population cohort of the ABCD study.
AB  - OBJECTIVE: Animal studies have shown that irisin is a myokine secreted following
      physical exercise, and that it induces the remodeling of white adipose tissue
      toward brown adipose tissue. Therefore, a protective role of irisin against
      obesity, diabetes, and other metabolic and cardiovascular conditions has been
      hypothesized. However, data in humans are contradictory and few data are
      available concerning the general population. DESIGN: We aimed to evaluate the
      association between serum irisin concentrations and habitual physical activity,
      as well as other metabolic and cardiovascular factors in a general population in
      a Mediterranean area. METHODS: We considered 858 consecutive individuals included
      in the ABCD (Alimentazione, Benessere Cardiovascolare e Diabete) study
      (ISRCTN15840340), a longitudinal observational single-center study of a cohort
      representative of the general population of Palermo, Sicily. Irisin serum
      concentrations (Phoenix Europe, Germany), habitual physical activity (HPA) level,
      and other blood and clinical variables were measured. RESULTS: The irisin serum
      concentrations were not normally distributed in the cohort (Shapiro-Wilk
      test=0.94; P<0.001). A significant association between irisin concentrations and
      HPA was observed (P<0.001). Irisin concentrations were higher in women than in
      men (P<0.01), and significantly correlated with serum concentrations of HDL
      cholesterol (P<0.05) and hs-C-reactive protein (hs-CRP; P<0.05). Binary logistic
      regression analysis demonstrated that high (? median value) irisin serum
      concentrations were significantly associated with female gender (OR=1.63; 95%
      CI=1.16-2.28), high serum hs-CRP concentrations (OR=1.61; 95% CI=1.02-2.54) and
      the HPA level (OR=1.42; 95% CI=1.02-1.96). CONCLUSIONS: Our study confirms, in a
      cohort of a general population, that irisin concentrations gradually increase
      with the usual level of habitual physical activity.

PMID- 29027534
TI  - Long non-coding RNA MEG3 promotes the proliferation of glioma cells through
      targeting Wnt/beta-catenin signal pathway.
AB  - Glioma has been identified as one of the most aggressive primary tumors. Long non
      coding RNAs (lncRNAs), with length larger than 200 bp, have drawn increasing
      attention to their abnormal expression and regulation function in carcinogenesis.
      However, the role of lncRNAs in glioma remains largely unknown. Maternally
      expressed gene 3 (MEG3), also known as gene-trap locus 2 (GTL2), is an imprinted
      gene, and is encoded by the MEG3 transcript of the DLK1/MEG3 locus on human
      chromosome, or Meg3 on mouse chromosome. In this study, we found that lncRNA MEG3
      was significantly downregulated in malignant glioma tissues and cell lines. The
      employment of the loss-of and gain-of functions assays presented that MEG3
      suppressed glioma cells proliferation and induced cell-cycle arrest. Furthermore,
      our findings showed that highly expressed MEG3 could weaken Wnt/beta-catenin
      signaling in glioma. Collectively, our findings revealed that downregulated
      lncRNA MEG3 could promote glioma cell proliferation through targeting Wnt/beta
      catenin signaling, which mainly influenced cell cycle.

PMID- 29027536
TI  - KRAS mutation of extraovarian implants of serous borderline tumor: prognostic
      indicator for adverse clinical outcome.
AB  - In contrast to non-invasive extraovarian implants, invasive implants of ovarian
      serous borderline tumor/atypical proliferative serous tumor are associated with
      adverse outcome and have been reclassified as low-grade serous carcinoma.
      Mutations of KRAS and/or BRAF have been reported in up to 50% of serous
      borderline tumor/atypical proliferative serous tumor. We investigated KRAS and
      BRAF mutation frequencies in the two types of implants of serous borderline
      tumor/atypical proliferative serous tumor in correlation with clinical outcome.
      Forty-two implants of serous borderline tumor from 39 patients were included
      (invasive implants/low-grade serous carcinoma, n=20; non-invasive implants,
      n=22). KRAS mutation was found in 12 of 20 invasive implants (60%) and 3 of 22
      non-invasive implants (14%). BRAF V600E mutation was found in 1 of 22 non
      invasive implants (5%) and none in invasive implants (0%). Invasive implants were
      more frequently associated with higher stage disease. Nine of 14 patients (64%)
      with KRAS mutation were found to have stage IIIC disease, while 5 of 24 patients
      (20%) without the mutation had stage IIIC disease. Patients with invasive
      implants had higher recurrence rate compared to those with non-invasive implants
      (60 vs 14 %, P=0.0003, log-rank test) and worse disease-specific survival
      (P=0.0008, log-rank test). Regardless of the histological subtypes, patients with
      KRAS mutation positive implants had significantly higher recurrence rate than
      those without the mutation (71 vs 21%, P=0.0021, log-rank test) and an
      unfavorable disease-specific survival (P=0.0104, log-rank test). In conclusion,
      compared to those with non-invasive implants, patients with invasive implants
      present with higher stage of the disease, higher recurrence rate and worse
      survival. KRAS mutation, but not BRAF V600E mutation, is significantly associated
      with invasive implants of serous borderline tumor. Regardless of the histological
      subtypes of the implants, KRAS mutation is a significant prognostic indicator for
      high risk of tumor recurrence and worse disease-specific survival.

PMID- 29027538
TI  - Gastrointestinal sodium absorption, microbiome, and hypertension.

PMID- 29027537
TI  - Optimal detection of clinically relevant mutations in colorectal carcinoma:
      sample pooling overcomes intra-tumoral heterogeneity.
AB  - Intra-tumoral genomic heterogeneity is a well-established biologic property of
      human malignancies with emerging roles in cancer progression and therapy
      resistance. However, its impact on the clinical utility of genomic testing in
      patient management remains unclear. Furthermore, best practices to account for
      heterogeneity in the provision of highly accurate, clinically valid molecular
      testing have yet to be firmly established. Genomic biomarkers for the management
      of colorectal carcinoma are both well-established (ie, KRAS, NRAS) and emerging
      (BRAF, PIK3CA, and others) in respect to therapy selection and clinical trial
      eligibility. Critically, standard colorectal carcinoma management requires the
      exclusion of KRAS and NRAS mutations; thus optimal procedures to control for
      potential intra-tumoral heterogeneity are clinically important. Here, we assessed
      heterogeneity among three intra-tumoral sites within 99 colorectal carcinomas
      cases on a CLIA-validated oncology next generation sequencing assay and examined
      whether a pooling strategy overcame any discordant results. Overall, 11% of cases
      demonstrated discordant mutation results between sites; 2% of cases were
      discrepant for mutations within RAS genes while the remainder was discrepant in
      PIK3CA. Half of the discrepant cases were associated with borderline tumor
      cellularity assessment. Further, a sample pooling strategy across all three sites
      successfully detected the relevant mutation in all but one case. Our results
      indicate that intra-tumoral genomic heterogeneity of clinically relevant genes
      within colorectal carcinoma is a relatively infrequent occurrence and that a
      simple strategy to pool DNA from several tumor sites with adequate cellularity
      minimizes the risk of false negative results even further to ensure optimal
      patient management.

PMID- 29027535
TI  - Transplant glomerulopathy.
AB  - In the renal allograft, transplant glomerulopathy represents a morphologic lesion
      and not a specific diagnosis. The hallmark pathologic feature is glomerular
      basement membrane reduplication by light microscopy or electron microscopy in the
      absence of immune complex deposits. Transplant glomerulopathy results from
      chronic, recurring endothelial cell injury that can be mediated by HLA
      alloantibodies (donor-specific antibodies), various autoantibodies, cell-mediated
      immune injury, thrombotic microangiopathy, or chronic hepatitis C. Clinically,
      transplant glomerulopathy may be silent, detectable on protocol biopsy, or
      present with overt manifestations, including up to nephrotic range proteinuria,
      hypertension, and declining glomerular filtration rate. In either case,
      transplant glomerulopathy is associated with reduced graft survival. This review
      details the morphologic features of transplant glomerulopathy found on light
      microscopy, immunofluorescence microscopy, and electron microscopy. The
      pathophysiology of the causes and risk factors are discussed. Clinical
      manifestations are emphasized and potential therapeutic modalities are examined.

PMID- 29027540
TI  - Dementia: Dementia prevention - a call for contextualized evidence.
AB  - This corrects the article DOI: 10.1038/nrneurol.2017.136.

PMID- 29027541
TI  - A systemic view of Alzheimer disease - insights from amyloid-beta metabolism
      beyond the brain.
AB  - This corrects the article DOI: 10.1038/nrneurol.2017.111.

PMID- 29027542
TI  - Stroke: Patients with CVT urgently need high-quality evidence.

PMID- 29027543
TI  - Motor neuron disease: Peripheral immune cell levels correlate with disease
      progression in ALS.

PMID- 29027539
TI  - Fatigue as a symptom or comorbidity of neurological diseases.
AB  - Fatigue, best described as an overwhelming feeling of tiredness and exhaustion,
      occurs in the context of various neurological diseases. The high prevalence of
      fatigue as either a symptom or a comorbidity of neurological disease must be
      taken seriously, as fatigue interferes with patients' activities of daily living,
      has a remarkable negative impact on quality of life, and is a major reason for
      early retirement. The tremendous consequences of fatigue are consistent across
      neurological diseases, as is the uncertainty concerning its underlying
      pathophysiological mechanisms. Inconsistencies in defining fatigue contribute to
      the present situation, in which fatigue represents one of the least-studied and
      least- understood conditions. Tools for assessing fatigue abound, but few can be
      recommended for clinical or research use. To make matters worse, evidence-based
      pharmacological treatment options are scarce. However, non-pharmacological
      approaches are currently promising and likely to become of increasing importance.
      In sum, fatigue is challenging for both health-care professionals and patients.
      The present article aims to provide a comprehensive review of the literature on
      fatigue in neurological disease, and to reveal its complexity, as well as
      weaknesses in the concept of fatigue itself.

PMID- 29027545
TI  - Synergistic treatment of TS.

PMID- 29027546
TI  - Letter to the Editor: Cerebral Hemorrhage following Chiropractic Activator
      Treatment-Case Report and Review of Literature.

PMID- 29027547
TI  - Robust Construction of Diffusion MRI Atlases with Correction for Inter-Subject
      Fiber Dispersion.
AB  - Construction of brain atlases is generally carried out using a two-step procedure
      involving registering a population of images to a common space and then fusing
      the aligned images to form an atlas. In practice, image registration is not
      perfect and simple averaging of the images will blur structures and cause
      artifacts. In diffusion MRI, this is further complicated by the possibility of
      within-voxel fiber misalignment due to natural inter-subject orientation
      dispersion. In this paper, we propose a method to improve the construction of
      diffusion atlases in light of inter-subject fiber dispersion. Our method involves
      a novel q-space (i.e., wavevector space) patch matching mechanism that is
      incorporated in a mean shift algorithm to seek the most probable signal at each
      point in q-space. Our method relies on the fact that the mean shift algorithm is
      a mode seeking algorithm that converges to the mode of a distribution and is
      hence robustness to outliers. Our method is therefore in effect seeking the most
      probable signal profile at each voxel given a distribution of profiles.
      Experimental results confirm that our method yields cleaner fiber orientation
      distribution functions with less artifacts caused by dispersion.

PMID- 29027544
TI  - Long-term effects of exercise and physical therapy in people with Parkinson
      disease.
AB  - Parkinson disease (PD) is a progressive, neurodegenerative movement disorder with
      symptoms reflecting various impairments and functional limitations, such as
      postural instability, gait disturbance, immobility and falls. In addition to
      pharmacological and surgical management of PD, exercise and physical therapy
      interventions are also being actively researched. This Review provides an
      overview of the effects of PD on physical activity - including muscle weakness,
      reduced aerobic capacity, gait impairment, balance disorders and falls.
      Previously published reviews have discussed only the short-term benefits of
      exercises and physical therapy for people with PD. However, owing to the
      progressive nature of PD, the present Review focuses on the long-term effects of
      such interventions. We also discuss exercise-induced neuroplasticity, present
      data on the possible risks and adverse effects of exercise training, make
      recommendations for clinical practice, and describe new treatment approaches.
      Evidence suggests that a minimum of 4 weeks of gait training or 8 weeks of
      balance training can have positive effects that persist for 3-12 months after
      treatment completion. Sustained strength training, aerobic training, tai chi or
      dance therapy lasting at least 12 weeks can produce long-term beneficial effects.
      Further studies are needed to verify disease-modifying effects of these
      interventions.

PMID- 29027548
TI  - Cu2+-Complex of hydrophilic nitrogen-rich polymer dots applied as a new MRI
      contrast agent.
AB  - We report on a novel Cu2+-complex of nitrogen-rich polymer dots for magnetic
      resonance imaging (MRI). The N-rich polymer dots are prepared from N-vinyl
      imidazole (VIm) by a one-pot hydrothermal synthesis at 220  degrees C (24 h) and
      used later on to fabricate a Cu2+-PVIm dot complex via efficient incorporation of
      Cu2+ into aqueous medium. The obtained Cu2+-PVIm dot complexes display relaxivity
      (r1 = 1.05 mM-1 s-1) two times higher than Cu2+ in aqueous solution (r1 = 0.43 mM
      1 s-1) and three times higher than Cu2+ in aqueous solution coordinated with VIm
      monomers (r1 = 0.32 mM-1 s-1), which show a remarkable contrast enhancement for
      T1-weighted MRI while efficiently labeling MCF-7 cells and other biomedical
      applications.

PMID- 29027549
TI  - Lifetime nanomanometry - high-pressure luminescence of up-converting lanthanide
      nanocrystals - SrF2:Yb3+,Er3.
AB  - Anti-Stokes luminescence of up-converting nanocrystals SrF2:Yb3+,Er3+ can be used
      as a high pressure optical sensor alternative to the ruby fluorescence-scale. In
      nanocrystalline SrF2:Yb3+,Er3+, high pressure reversibly shortens the emission
      lifetimes nearly linearly up to 5.29 GPa at least. Its advantage is the use of
      NIR (~980 nm) radiation, highly penetrable for many materials. The shortening of
      up-conversion lifetimes has been attributed mainly to the changes in energy
      transfer rates, caused by decreased interatomic distances and increased overlap
      integrals between 4f electrons and the valence shells of ligand ions. The origin
      of high-pressure effects on the luminescence intensity, band ratio and their
      spectral position has been explained by the increased interactions and
      distortions of the crystal-field symmetry around the emitting ions in the
      compressed structure.

PMID- 29027550
TI  - Enhanced intersystem crossing in carbonylpyrenes.
AB  - Ultrafast intersystem crossing of carbonylpyrenes in chloroform was investigated
      by femtosecond pump-probe spectroscopy. When compared to the dominant
      fluorescence decay pathway in pyrene, carbonyl functionalized pyrenes display
      near-unity triplet formation upon photoexcitation. The excited singlet state (Sp)
      undergoes rapid intersystem crossing (kISC) concomitantly with internal
      conversion (kIC) to lower excited singlet states (Sn) within a timescale of 5-11
      ps (1/tau2 = kIC + kISC). Furthermore, intersystem crossing from lower excited
      singlet states (Sn) proceeds through coupling with receiver triplet states,
      eventually leading to high triplet quantum yields (PhiT = 97%;
      tetraacetylpyrene). Followed by internal conversion in the triplet manifolds,
      phosphorescence decay on a microsecond timescale is observed from the emitter
      triplet state.

PMID- 29027551
TI  - Synthesis of free-standing Ta3N5 nanotube membranes and flow-through visible
      light photocatalytic applications.
AB  - We report on free-standing Ta3N5 nanotubular membranes with open top and bottom,
      used as visible-light-active, flow-through photocatalytic micro-reactors. We grow
      first a robust anodic Ta2O5 layer, lift-off a membrane and convert to Ta3N5. Such
      membranes can easily, in a flow-through mode, degrade methylene blue under
      visible light (wavelength >400 nm) or solar illumination.

PMID- 29027552
TI  - Uniform carbon dots@TiO2 nanotube arrays with full spectrum wavelength light
      activation for efficient dye degradation and overall water splitting.
AB  - This work presents a novel approach for preparing photocatalysts based on TiO2
      nanotube arrays (TiO2 NTAs) anchored with carbon dots (CDs) by a facile two-step
      method which includes an electrochemical anodization technique followed by
      electrochemical deposition. The synthesized high quality graphitic carbon dots
      can act as sensitizers to extend the spectral range of light absorption towards
      the full solar spectrum. It is confirmed that TiO2 NTAs anchored with CDs
      (CDs/TiO2 NTAs) display greatly improved photocatalytic activity and excellent
      photocatalytic stability. By tuning the light absorption of the TiO2 NTAs, the
      utilization of light in charge generation and separation is well synergized with
      the CDs for enhanced photocatalytic pollutant degradation and water splitting,
      achieving significantly improved rates of photocatalytic degradation and H2
      production in the visible and full spectra, respectively.

PMID- 29027553
TI  - [Pb3Cu2I10(phen)4]n: a novel organic-inorganic hybrid ferromagnetic
      semiconductor.
AB  - An iodoplumbate-based organic-inorganic hybrid ferromagnetic semiconductor,
      [Pb3Cu2I10(phen)4]n, has been solvothermally synthesized. The ferromagnetic
      exchange interaction is resulting from the multiple aromatic pi-pi stacking
      interactions between the adjacent phen molecules.

PMID- 29027554
TI  - Magnetic behaviour of bimetallic layered phases M'0.2Mn0.8PS3.0.25 H2O (M' =
      ZnII, CuII, NiII, CoII).
AB  - In this work the magnetic properties of bimetallic phases M'0.2Mn0.8PS3.0.25H2O
      (M' = CoII, NiII, CuII or ZnII) have been explored and compared with those of the
      pristine phase MnPS3. Magnetic susceptibility, high field magnetization and
      electron paramagnetic resonance (EPR) studies reveal that the transition
      temperature between the antiferromagnetic and paramagnetic order for the pristine
      phase is shifted to lower values in the bimetallic phases. From magnetization
      measurements the critical field of the spin-flop transition is found to be
      dependent on the nature of the added secondary transition metal ion. EPR spectra
      of all compounds in the temperature range of 8-300 K present a single resonance
      line shape. Temperature dependence of the EPR parameters, like line width, g
      values and double integrated area (IDIN), are obtained from the spectra and
      present a scenario compatible with the magnetization results. The temperature
      dependence of the first derivative of the product (IDINT) shows two maxima for
      all samples, with exception of the CoII phase, indicating two critical
      temperatures, while these critical temperatures could not be clearly determined
      by dc susceptibility.

PMID- 29027555
TI  - Formation of ordered mesostructured TiO2 thin films: a soft coarse-grained
      simulation study.
AB  - Ordered mesostructured TiO2 thin films are employed in diverse applications
      ranging from catalysis and sensing, to photovoltaic and lithium-ion batteries.
      Experimentally these mesostructured thin films are fabricated via a sol-gel
      process coupled with evaporation-induced self-assembly of a supramolecular
      template, where the concentration of hydrogen chloride (HCl) and water play vital
      roles. We employ a soft, coarse-grained model of the amphiphilic template Brij58
      and spherical particles, representing titanium-oxo clusters, to study the role of
      HCl and water in the formation of mesostructured TiO2 thin films. The template
      cluster and cluster-cluster interactions are reflected in the interaction terms
      deltaNBP and epsilonPP, respectively. The results show that a decrease in HCl
      (increase in epsilonPP) leads to the formation of large mesopores due to the
      strong attraction between particles, giving rise to a high dispersity index (low
      order) of the thin films. However, a decrease in water (increase in deltaNBP)
      will compensate for the entropic attraction between particles, resulting in thin
      films with low dispersity index (high order). The variation of the dispersity
      index in the deltaNBP-epsilonPP plane provides an intuitive understanding that
      the slow evaporation of HCl could drive the film towards a uniform mesoporous
      state, whereas fast evaporation pushes the film through a non-uniform phase.
      These results indicate that even if the mass proportion of the surfactants Brij58
      and titanium precursors is the same in the initial solution, the final mesoporous
      structures could be diverse, which was confirmed by the controlled experiments.
      We also confirm the post-processing-towards-order strategy by making the particle
      rearrangement available by weakening the epsilonPP. The outlined procedure paves
      the way for soft, coarse-grained models to understand the complex co-assembly of
      transition metal clusters and amphiphilic surfactants towards the rational design
      of highly ordered mesoporous structures.

PMID- 29027556
TI  - Effect of a heavy heteroatom on triplet formation and interactions in single
      conjugated polymer molecules and aggregates.
AB  - Triplet formation and interactions with emissive singlet excitons are
      investigated in poly(3-hexylselenophene) (P3HS) using single molecule
      spectroscopy. P3HS is a heavy atom analog of the more commonly studied poly(3
      hexylthiophene) (P3HT), a benchmark polymer for solar cells. P3HS tends to
      aggregate strongly which necessitates dilution to ultra-low levels within a solid
      inert host in order to resolve photophysical responses of single chains.
      Fluorescence excitation intensity modulation is performed on isolated P3HS chains
      using a sequence of rectangular pulses of varying intensities to probe the
      presence of spin-forbidden triplet excitons. Triplet population dynamics
      originating from singlet-triplet and triplet-triplet interactions appear as
      quenching of the initial fluorescence intensity to steady-state levels on
      characteristic time scales of ~1-10 MUs. Over 80% of all molecules studied
      display significant fluorescence intensity modulation (quenching depths >50%)
      indicative of efficient intersystem crossing and large triplet occupancies.
      Because triplets are highly localized and singlet-triplet and triplet-triplet
      annihilation rate constants are comparable to those of intersystem crossing,
      multiple triplets are present at any given time on single P3HS chains. Triplet
      lifetimes were estimated to be ~4 MUs (upper limit) determined from recovery to
      the ground electronic singlet state in the absence of light and, surprisingly,
      triplets vanish at the onset of P3HS aggregation. This result was unexpected
      since P3HS triplet formation takes place on time scales <30 ps making this
      process competitive with most accessible non-radiative deactivation pathways.

PMID- 29027557
TI  - Ionic-surfactant-coated subtilisin: activity, enantioselectivity, and application
      to dynamic kinetic resolution of secondary alcohols.
AB  - In this work, we explored the utility of ionic-surfactant-coated Bacillus
      licheniformis subtilisin (ISCBLS) as the catalyst for the dynamic kinetic
      resolution of secondary alcohols. ISCBLS was prepared by freeze-drying Bacillus
      licheniformis subtilisin with both ionic surfactant 1 and dextrin. ISCBCL
      displayed 9300-fold enhanced activity relative to its native counterpart in the
      transesterificaion of N-acetyl phenylalanine ethyl ester with 1-propanol in
      hexane and 12 800-fold enhanced activity in the transesterification of
      trifluoroethyl butyrate with 1-phenylethanol in THF. The enantioselectivity of
      ISCBLS was examined with 50 secondary alcohols as the substrates for kinetic
      resolution in the presence of trifluoroethyl butyrate. ISCBLS displayed
      synthetically useful enantioselectivity for most of the secondary alcohols
      tested. The enantioselectivity of ISCBLS was in particular good to high for m- or
      p-substituted 1-phenylethanols. The DKRs of these secondary alcohols by the
      combination of ISCBLS and a ruthenium-based racemization catalyst provided the
      products of (S)-configuration with good results (80-94% yield, 90-99% ee). It is
      concluded that ISCBLS is of great use as the enantiocomplementary counterpart of
      (R)-selective lipase for the dynamic kinetic resolution of secondary alcohols.

PMID- 29027558
TI  - Selective engineering of oxygen-containing functional groups using the alkyl
      ligand oleylamine for revealing the luminescence mechanism of graphene oxide
      quantum dots.
AB  - Oxygen-containing functional groups such as epoxy, hydroxyl, carboxylic, and
      carboxyl groups have a great influence on the luminescence properties of graphene
      oxide quantum dots (GOQDs). Understanding their roles is essential for the design
      and optimization of GOQD performance. Herein, we investigate the effect of
      epoxide functional groups in GOQDs on the luminescence mechanism through
      passivation of the epoxide functional groups using the alkyl ligand oleylamine.
      Luminescence in the as-synthesized GOQDs has two separate origins: intrinsic
      states derived from localized sp2 carbon subdomains and extrinsic states formed
      by oxygen-functional groups. When the oleylamine ligand is conjugated on the
      GOQDs, intrinsic PL emission from the localized sp2 carbon subdomains decreases.
      This is discussed in detail, based on optical characterization and first
      principles density functional theory calculations, which reveal that the role of
      the epoxide functional groups is to form localized sp2 carbon subdomains emitting
      intrinsic PL. To the best of our knowledge, this is the first investigation of
      the role of epoxide functional groups on the luminescence mechanism in GOQDs.

PMID- 29027559
TI  - Photosensitised regioselective [2+2]-cycloaddition of cinnamates and related
      alkenes.
AB  - An efficient method for the synthesis of substituted cyclobutanes from
      cinnamates, chalcones, and styrenes has been developed utilizing a visible-light
      triplet sensitisation mode. This reaction provides a diverse range of substituted
      cyclobutanes in high yields under mild conditions without the need of external
      additives. Good regioselectivity is obtained due to strong pi-pi-stacking of
      arene moieties, whereas diastereoselectivity relies on the electronic effects or
      ortho-substitution of the arene substrate. The utility of this transformation is
      demonstrated by the formal synthesis of the lignane natural product (+/-)
      Tanegool.

PMID- 29027560
TI  - Recovered spinel MnCo2O4 from spent lithium-ion batteries for enhanced
      electrocatalytic oxygen evolution in alkaline medium.
AB  - A facile way of recovering 3d transition metals of industrial importance from
      spent lithium-ion batteries (LIBs) without using any surfactants has been
      developed. Mn- and Co-rich spent LIBs were chosen as sustainable sources for
      recovering the oxides of the respective elements. The physical dismantling of Li
      ion batteries, chemical leaching with 2 M acetic acid, precipitation with
      ammonium carbonate, hydrothermal conditioning and calcination at 650  degrees C
      led to the facile formation of spherical spinel MnCo2O4 with very high
      morphological selectivity. The obtained spherical MnCo2O4 was identified by
      various advanced characterization techniques. Detailed electrochemical
      characterization revealed that the recovered spheres of spinel MnCo2O4 were
      effective in catalyzing the oxygen evolution reaction (OER) in 1 M KOH and
      required an overpotential of 358 and 400 mV to generate a current density of 5
      and 10 mA cm-2, respectively, with a relatively low catalyst loading (0.001025 g
      cm-2). Comparative electrocatalytic studies carried out with recovered LiCoO2,
      recovered LiXMnOX+1 and commercially available catalysts such as RuO2 (c-RuO2),
      Co3O4 (c-Co3O4) and MnO2 (c-MnO2) revealed that the recovered spheres of spinel
      MnCo2O4 were more effective OER catalysts than the recovered LiCoO2, recovered
      LiXMnOX+1, c-Co3O4 and c-MnO2 and exhibited comparable activity to that of c-RuO2
      with very little difference in overpotential (~50 mV) at current densities of 5
      and 10 mA cm-2. With such a low catalyst loading, the observed electrocatalytic
      performance in water oxidation of a material recovered from waste is highly
      significant and will surely attain greater industrial importance when the
      recycling of spent LIBs from electronic wastes is considered.

PMID- 29027561
TI  - Influence of temperature gradients on charge transport in asymmetric
      nanochannels.
AB  - Charge selective asymmetric nanochannels are used for a variety of applications,
      such as nanofluidic sensing devices and energy conversion applications. In this
      paper, we numerically investigate the influence of an applied temperature
      difference over tapered nanochannels on the resulting charge transport and flow
      behavior. Using a temperature-dependent formulation of the coupled Poisson-Nernst
      Planck and Navier-Stokes equations, various nanochannel geometries are
      investigated. Temperature has a large influence on the total ion transport, as
      the diffusivity of ions and viscosity of the solution are strongly affected by
      temperature. We find that the selectivity of the nanochannels is enhanced with
      increasing asymmetry ratios, while the total current is reduced at higher
      asymmetry cases. Most interestingly, we find that applying a temperature gradient
      along the electric field and along the asymmetry direction of the nanochannel
      enhances the selectivity of the tapered channels even further, while a
      temperature gradient countering the electric field reduces the selectivity of the
      nanochannel. Current rectification is enhanced in asymmetric nanochannels if a
      temperature gradient is applied, independent of the direction of the temperature
      difference. However, the degree of rectification is dependent on the direction of
      the temperature gradient with respect to the channel geometry and the electric
      field direction. The enhanced selectivity of nanochannels due to applied
      temperature gradients could result in more efficient operation in energy
      harvesting or desalination applications, motivating experimental investigations.

PMID- 29027562
TI  - Monomeric and dimeric coordinatively saturated and substitutionally inert Ru(ii)
      polypyridyl complexes as anticancer drug candidates.
AB  - Due to the increasing impact of cancer on worldwide mortality, more and more
      attention is being devoted to the investigation of novel anticancer strategies.
      Among these, chemotherapy plays a key role in fighting cancer. This explains the
      increasing engagement of both the pharmaceutical industry and academia towards
      the discovery of new chemotherapeutic agents. In recent years, metal-based drugs
      have attracted much attention due to their atypical physico-chemical properties
      compared to organic molecules. After the approval of cisplatin as a
      chemotherapeutic agent in 1978, several types of metal-based drugs have been
      explored. Among them, Ru-based anticancer drug candidates have become a central
      subject in this research field. However, most of the Ru-based compounds
      investigated over the last two decades express their cytotoxicity with a
      mechanism of action involving, among others, a ligand-exchange mechanism. In this
      Review, we give a complete overview of a specific class of antiproliferative
      ruthenium complexes, namely coordinatively saturated and substitutionally inert
      Ru(ii) polypyridyl complexes. This implies that the cytotoxicity observed comes
      from the entire complex and not from ligand-exchange. In this Review, we present
      monomeric and dimeric Ru(ii) polypyridyl complexes, which have been found to be
      toxic to cancer cells. More specifically, monomeric Ru(ii) polypyridyl complexes
      are analysed considering their direct interaction or not with DNA as the cause of
      cell death, while dimeric Ru(ii) polypyridyl complexes are classified according
      to their biological targets. Very importantly, the cellular targets of these
      complexes are discussed in detail. Indeed, several targets were identified and
      different mechanisms of action were suggested.

PMID- 29027563
TI  - Improved device performances based on Si quantum dot/Si nanowire hetero
      structures by inserting an Al2O3 thin layer.
AB  - Si quantum dot-based light emitting devices were fabricated on Si nanowire arrays
      in order to improve light extraction efficiency. However, the device performance
      is deteriorated by using Si nanowires with a depth of 1.2 MUm due to serious
      surface recombination. By introducing an Al2O3 thin layer between the Si quantum
      dots and Si nanowires, significantly enhanced electroluminescence (~8.5 fold) has
      been demonstrated. Based on electron spin resonance, capacitance-voltage and
      conductance-voltage measurements, the effect of the Al2O3 thin layer on the
      improvement of device performance is quantitatively evaluated. Our results
      demonstrate that besides the chemical passivation to reduce the surface defect
      states of Si nanowires, the Al2O3 thin layer can act as a barrier layer to
      confine the injected carriers in the active Si quantum dot layer due to the
      existence of negatively fixed charges and a potential barrier. As a consequence,
      radiative recombination is promoted which contributes to the enhanced light
      emission from devices based on Si quantum dot/Si nanowire hetero-structures.

PMID- 29027565
TI  - ?

PMID- 29027564
TI  - Correction to: Complete mucosal healing of distal lesions induced by twice-daily
      budesonide 2-mg foam promoted clinical remission of mild-to-moderate ulcerative
      colitis with distal active inflammation: double-blind, randomized study.
AB  - In Fig. 2(c) of this article, the length of the "95% CI difference bars" under
      the items labelled "Left-sided and Pancolitis" and "Left-sided" under the heading
      "Disease type" was corrected. The correct figure is shown in the following page.

PMID- 29027566
TI  - ?

PMID- 29027567
TI  - Commentary on: Laparoscopic sacrocolpopexy compared with open abdominal
      sacrocolpopexy for vault prolapse repair: a randomised controlled trial.

PMID- 29027568
TI  - [Diagnostics and treatment of acromegaly : Necessity for targeted monitoring of
      comorbidities].
AB  - Acromegaly is a rare and severe condition, presenting with typical signs and
      symptoms. The diagnosis is often initially made years after the first
      manifestations of the disease. In more than 99% of patients the disease is caused
      by a benign pituitary tumor that secretes growth hormone (GH). The diagnosis is
      based on the presence of increased insulin-like growth factor 1 (IGF-1) levels
      and a lack of GH suppression in the oral glucose tolerance test. The standard
      imaging procedure for tumor detection is magnetic resonance imaging in the region
      of the sella turcica. Treatment includes surgical, drug and radiation therapy.
      Important factors are an intensive aftercare of the patient, controls for
      detection of tumor recurrence and pituitary insufficiency as well as assessment
      of various organ functions and risk constellations. Patient care should involve
      close cooperation between endocrinologists, neurosurgeons and general
      practitioners as well as other specialist disciplines.

PMID- 29027569
TI  - Epidemiology of clavicle fractures in a level 1 trauma center in Belgium.
AB  - PURPOSE: In the last 10 years, there has been an increasing tendency toward
      operative fixation of clavicle fractures. In this retrospective analysis, we will
      demographically assess all patients who sustained a clavicle fracture and were
      treated in our university hospital between 2004 and 2014. METHODS: We
      retrospectively updated our database and analyzed all adult patients who were
      diagnosed with a clavicle fracture in our hospital. The following parameters were
      included in the database: age, gender, Robinson classification, date of trauma,
      injury mechanism, time until surgery, and reason for delayed surgery. Descriptive
      statistics were used to describe differences between patient groups and linear
      regression was performed to identify trends over time. RESULTS: 667 patients were
      included for analysis. The mean age was 43 +/- 17.7 years. The majority of
      clavicle fractures occurred due to bicycle injuries (35.3%) and these increased
      from 2004 until 2014 (r = 0.738, R2 = 0.545, p = 0.009). Patients with a midshaft
      clavicle fracture were increasingly treated primarily surgically (r = 0.928, R2 =
      0.861, p < 0.0001). There was an increased ratio of delayed surgery in relation
      to age from the age of 16 (9.1%) until the age of 70 years (37.2%). CONCLUSIONS:
      There is an increasing number of fractures sustained by bicycle accidents and an
      increasing number of patients undergoing operative treatment. Middle-aged
      patients more often had delayed surgery compared with young adult patients. This
      could be due to an increased activity level of the elder population and the
      concomitant demand for a faster return to activities. LEVEL OF EVIDENCE: III,
      retrospective comparative study.

PMID- 29027570
TI  - Are We Right to Consider Mesenchymal Stem Cells to Be a New Perspective for
      Patients with Juvenile Idiopathic Arthritis?
AB  - Juvenile idiopathic arthritis (JIA) is the most common cause of chronic arthritis
      in childhood. Up to 50% of patients are resistant to standard therapy, which
      includes non-steroid anti-inflammatory drugs, corticosteroids, disease-modifying
      anti-rheumatic drugs and biologic therapies. Intra-articular injection of
      mesenchymal stem cells (MSCs) is proposed as a new approach to JIA treatment.
      MSCs can modulate inflammation via mechanisms of both adaptive and innate immune
      response. They are able to inhibit T and B cell proliferation, promote regulatory
      T cells, suppress the maturation of dendritic cells, stimulate macrophage
      differentiation into M2 phenotype and reduce effectiveness of natural killer
      cells. They also secrete plethora of soluble factors which influence joint
      inflammation. Recent clinical studies reviewed in the article provide promising
      results which may suggest including intra-articular injection of MSCs in therapy
      of patients with oligoarticular JIA.

PMID- 29027571
TI  - Ingestion and Egestion of Microplastics by the Cladoceran Daphnia magna: Effects
      of Regular and Irregular Shaped Plastic and Sorbed Phenanthrene.
AB  - The presence of microplastics in aquatic ecosystems is of increasing global
      concern. This study investigated ingestion, egestion and acute effects of
      polyethylene microplastics in Daphnia magna. Fate of regular shaped microplastic
      beads (10-106 um) were compared with irregular shaped microplastic fragments (10
      75 um). Daphnia magna ingested regular and irregular microplastic with uptake
      between 0.7 and 50 plastic particles/animal/day when exposed to microplastic
      concentrations of 0.0001-10 g/L. Egestion of irregular fragments was slower than
      that of microplastic beads. The EC50 for irregular microplastic was 0.065 g/L
      whereas microplastic beads were less inhibitory. The potential of microplastic to
      act as vector for hydrophobic pollutants was examined using [14C]phenanthrene as
      tracer. Polyethylene microplastic sorbed less [14C]phenanthrene compared to
      natural plankton organisms (bacteria, algae, yeast). As microplastics are much
      less abundant in most aquatic ecosystems compared to plankton organisms this
      suggests a limited role as vector for hydrophobic pollutants under current
      environmental conditions.

PMID- 29027572
TI  - Correction to: Highlights of the annual scientific meeting of the 24th congress
      of the European Society of Musculoskeletal Radiology (ESSR) 2017.
AB  - The original version of this article unfortunately contained mistakes. The name
      and affiliations of Luca Maria Sconfienza are already corrected on this article.

PMID- 29027573
TI  - Dose reduction for fluoroscopically guided injections: phantom simulation and
      patient procedures.
AB  - OBJECTIVE: To demonstrate fluoroscopy dose reduction through both simulated
      injections on a phantom and patient injections. MATERIALS AND METHODS: Our study
      was IRB-approved and HIPAA-compliant. Simulation on a phantom was used to
      estimate effective dose, entrance dose, and organ doses for hip joint injections
      without and with dose minimization technique (DMT). Additionally, 1,094 joint,
      bursae, and tendon sheath injections performed by three operators in the same
      fluoroscopy suite were evaluated both before and after application of DMT.
      Fluoroscopy time (FT), dose, and dose area product (DAP) of injections were
      compared using unpaired t-tests with P > 0.05 considered statistically
      significant. RESULTS: For the phantom simulation comparing injections without DMT
      and with DMT, the total DAP was 191.7 vs 18.7 MUGy.m2, and the entrance dose was
      10.2 vs 3.6 mGy, respectively. For both men and women, DMT reduces effective dose
      and organ doses. For all injections, the FT (0.7 to 0.2 min), dose (5.6 to 1.9
      mGy), and DAP (56.9 to 19.1 MUGy.m2) for all three operators decreased with DMT
      and remained statistically significant when stratified by the two most common
      injections, glenohumeral and hip joint injections (P < 0.05). CONCLUSIONS: FT,
      effective dose, entrance dose, and DAP can be reduced with the use of simple easy
      to-learn techniques, which will benefit both the patient and the radiologist.

PMID- 29027574
TI  - The prognostic significance of serum XCL1 concentration in patients with acute
      lymphoblastic leukemia: a pilot study.
AB  - There is no information about XCL1 in patients with acute lymphoblastic leukemia
      (ALL). The objective of this study was to correlate the serum levels of XCL1 and
      survival in ALL patients. Only ALL patients older than 12 months were considered
      to participate. Serum XCL1 was measured at diagnosis, end of remission induction,
      and end of consolidation. Thirty-three ALL patients with median age of 21 years
      (1-78) were included. Higher XCL1 level (above 50 pg/mL) at ALL diagnosis
      correlated with higher survival (p = 0.038), whereas XCL1 level at end of
      induction and consolidation had no significant correlation. Concerning the
      behavior of serum XCL1 during treatment, higher survival at 5 years was observed
      in the group with progressively decreased levels of XCL1 (70%) than those with
      progressively increasing (29%) or no detectable XCL1 (14%). In conclusion, higher
      serum XCL1 levels at diagnosis and their progressive decline throughout
      chemotherapy could be correlated with higher survival.

PMID- 29027575
TI  - Transmission modes of a pesticide-degrading symbiont of the oriental fruit fly
      Bactrocera dorsalis (Hendel).
AB  - Symbionts are associated with many insects and play several multifunctional roles
      in insect-microorganism mutualistic relationships. The trichlorphon-degrading
      symbiont Citrobacter freundii (CF-BD) of the oriental fruit fly Bactrocera
      dorsalis was recently discovered; however, its intraspecies transmission pathway
      among flies remains unknown. Here, we use fluorescence in situ hybridization
      (FISH), PCR detection, and a series of ingenious experiments to reveal that CF-BD
      was aggregated in rectal pads associated with the female ovipositor, and the CF
      BD symbiont was vertically transmitted via egg surface contamination. Although CF
      BD was not detected in ovaries, it was found in deposited eggs. In addition, CF
      BD was readily acquired horizontally between larvae or adults via oral uptake,
      although it was not transferred via mating behavior. Surface sterilization of
      eggs had a negative effect on the insects, which exhibited a lower body weight
      and a sharp decrease in fecundity, suggesting important biological roles of CF-BD
      in the fitness of the host insects. Our findings may also help to explain the
      high pesticide resistance levels of B. dorsalis. Furthermore, identifying a clear
      transmission pathway of this organophosphorus-degrading symbiont will be useful
      for pesticide resistance management and future pest control technologies.

PMID- 29027576
TI  - Neonatal ulcerative colitis associated with Familial Mediterranean fever: a case
      report.
AB  - Neonatal inflammatory bowel disease (IBD) is a subclass of very early onset IBD
      that includes children younger than 1 month. It is characterized by more colonic
      involvement and monogenetic etiology, resistance to classical anti
      inflammatory/immunomodulatory treatments and associated with colitis in first
      degree family members. Herein we report a 3 month-old girl who was admitted with
      bloody diarrhea since 10 days of age. Her symptoms persist despite diet
      elimination. She was diagnosed with neonatal ulcerative colitis (UC) based on
      clinical, laboratory and histopathological examination. But, she was unresponsive
      to the immunosuppressive therapy. On the follow-up, she was hospitalized for the
      high fever two times. Genetic analysis revealed homozygote M694 V mutation.
      Bloody diarrhea and other clinical findings were improved after colchicine
      therapy. Neonatal UC associated with Familial Mediterranean fever is an extremely
      rare condition and to the best of our knowledge our case is the first case in
      literature. Early diagnosis autoinflammatory disease may prevent complications
      related to unnecessary immunosuppressive drug usage and the risk of development
      of amyloidosis associated with autoinflammatory disorders.

PMID- 29027578
TI  - Ectopic expression of UGT84A2 delayed flowering by indole-3-butyric acid-mediated
      transcriptional repression of ARF6 and ARF8 genes in Arabidopsis.
AB  - KEY MESSAGE: Ectopic expression of auxin glycosyltransferase UGT84A2 in
      Arabidopsis can delay flowering through increased indole-3-butyric acid and
      suppressed transcription of ARF6, ARF8 and flowering-related genes FT, SOC1, AP1
      and LFY. Auxins are critical regulators for plant growth and developmental
      processes. Auxin homeostasis is thus an important issue for plant biology. Here,
      we identified an indole-3-butyric acid (IBA)-specific glycosyltransferase,
      UGT84A2, and characterized its role in Arabidopsis flowering development. UGT84A2
      could catalyze the glycosylation of IBA, but not indole-3-acetic acid (IAA).
      UGT84A2 transcription expression was clearly induced by IBA. When ectopically
      expressing in Arabidopsis, UGT84A2 caused obvious delay in flowering.
      Correspondingly, the increase of IBA level, the down-regulation of AUXIN RESPONSE
      FACTOR 6 (ARF6) and ARF8, and the down-regulation of flowering-related genes such
      as FLOWERING LOCUS T (FT), SUPPRESSOR OF OVEREXPRESSION OF CO1(SOC1), APETALA1
      (AP1), and LEAFY(LFY) were observed in transgenic plants. When exogenously
      applying IBA to wild-type plants, the late flowering phenotype, the down
      regulation of ARF6, ARF8 and flowering-related genes recurred. We examined the
      arf6arf8 double mutants and found that the expression of flowering-related genes
      was also substantially decreased in these mutants. Together, our results suggest
      that glycosyltransferase UGT84A2 may be involved in flowering regulation through
      indole-3-butyric acid-mediated transcriptional repression of ARF6, ARF8 and
      downstream flowering pathway genes.

PMID- 29027577
TI  - Assessment of renal perfusion impairment in a rat model of acute renal congestion
      using contrast-enhanced ultrasonography.
AB  - Renal congestion is caused by elevated central venous pressure (CVP), and
      decreases glomerular filtration in patients with congestive heart failure. Since
      real-time contrast-enhanced ultrasonography (CEUS) using microbubble-based
      contrast agents can visualize the perfused microvascular bed, we sought to
      evaluate the impairment of renal perfusion during acute renal congestion with
      CEUS. In Wister rats, CEUS of kidney was performed with the direct monitoring of
      CVP and intra-renal pressure (IRP). When CVP was elevated to 10 and 15 mmHg after
      the bolus injection of normal saline via the femoral vein, peak intensity (PI,
      dB) and time to PI (TTP) in the renal cortex and medulla were compared with
      control rats. There was a strong correlation between IRP and CVP (r = 0.95, p <
      0.0001). In the congestion model, more time was required for enhancement of the
      parenchyma, especially in the medulla compared to control; TTP of the medulla and
      cortex at 15 mmHg CVP (CVP15) was significantly prolonged compared with controls
      (medulla, 4351 +/- 98 vs. 1415 +/- 267 ms, p = 0.003; cortex, 3219 +/- 106 vs.
      1335 +/- 264 ms, p = 0.005). In addition, medullary PI at CVP15 decreased, but
      not significantly, compared to those of controls and at 10 mmHg CVP (20.1 +/-
      0.9, 22.8 +/- 1.6, 21.6 +/- 0.2 dB). In contrast, cortical PIs at CVP15 were
      significantly lower than that of control (24.6 +/- 1.0 vs. 31.4 +/- 1.0 dB, p =
      0.007). CEUS revealed that impaired renal parenchymal flow in an acute congestion
      model is accompanied with increased renal interstitial pressure.

PMID- 29027579
TI  - DNA-methylation profiling discloses significant advantages over NanoString method
      for molecular classification of medulloblastoma.

PMID- 29027581
TI  - Unusual case of coronal complete bladder duplication associated with
      rectoprostatic fistula to duplicated prostatic urethra.
AB  - Anorectal malformations are a common congenital anomaly, while bladder
      duplication is rare. Bladder duplications are classified as complete or
      incomplete and sagittal or coronal. We present a rare case of coronal complete
      bladder duplication with rectoprostatic fistula to the blind ending prostatic
      urethra of the duplicated bladder.

PMID- 29027580
TI  - Screening for amyloid proteins in the yeast proteome.
AB  - The search for novel pathological and functional amyloids represents one of the
      most important tasks of contemporary biomedicine. Formation of pathological
      amyloid fibrils in the aging brain causes incurable neurodegenerative disorders
      such as Alzheimer's, Parkinson's Huntington's diseases. At the same time, a set
      of amyloids regulates vital processes in archaea, prokaryotes and eukaryotes. Our
      knowledge of the prevalence and biological significance of amyloids is limited
      due to the lack of universal methods for their identification. Here, using our
      original method of proteomic screening PSIA-LC-MALDI, we identified a number of
      proteins that form amyloid-like detergent-resistant aggregates in Saccharomyces
      cerevisiae. We revealed in yeast strains of different origin known yeast prions,
      prion-associated proteins, and a set of proteins whose amyloid properties were
      not shown before. A substantial number of the identified proteins are cell wall
      components, suggesting that amyloids may play important roles in the formation of
      this extracellular protective sheath. Two proteins identified in our screen, Gas1
      and Ygp1, involved in biogenesis of the yeast cell wall, were selected for
      detailed analysis of amyloid properties. We show that Gas1 and Ygp1 demonstrate
      amyloid properties both in vivo in yeast cells and using the bacteria-based
      system C-DAG. Taken together, our data show that this proteomic approach is very
      useful for identification of novel amyloids.

PMID- 29027582
TI  - Bioleaching of Gold and Silver from Waste Printed Circuit Boards by Pseudomonas
      balearica SAE1 Isolated from an e-Waste Recycling Facility.
AB  - Indigenous bacterial strain Pseudomonas balearica SAE1, tolerant to e-waste
      toxicity was isolated from an e-waste recycling facility Exigo Recycling Pvt.
      Ltd., India. Toxicity tolerance of bacterial strain was analyzed using crushed
      (particle size <=150 um) waste computer printed circuit boards (PCBs)/liter (L)
      of culture medium. The EC50 value for SAE1 was 325.7 g/L of the e-waste pulp
      density. Two-step bioleaching was then applied to achieve the dissolution of gold
      (Au) and silver (Ag) from the e-waste. To maximize precious metal dissolution,
      factors including pulp density, glycine concentration, pH level, and temperature
      were optimized. The optimization resulted in 68.5 and 33.8% of Au and Ag
      dissolution, respectively, at a pH of 9.0, a pulp density of 10 g/L, a
      temperature of 30  degrees C, and a glycine concentration of 5 g/L. This is the
      first study of Au and Ag bioleaching using indigenous e-waste bacteria and its
      analysis to determine e-waste toxicity tolerance.

PMID- 29027583
TI  - Changes in circulating cell-free DNA and nucleosomes in patients with exacerbated
      psoriasis.
AB  - Psoriasis is a multifactorial chronic inflammatory disease. We aimed to examine
      blood levels of nucleosomes derived from apoptotic cells, nucleosomal cell-free
      DNA (cfDNA) and immune-inflammatory biomarkers tumor necrosis factor-alpha (TNF
      alpha), C-reactive protein (CRP), and interleukin 6 (IL-6) in psoriatic subjects.
      The study included 28 patients with exacerbated psoriasis vulgaris and 22
      controls. The clinical and laboratory investigations included the determination
      of PASI score, BMI, cfDNA (by real-time PCR), nucleosomes, TNF-alpha, CRP, and IL
      6. The range of PASI score in psoriatic patients was 10-34 (median 19). In the
      patients, we found significantly elevated levels (p < 0.001) of cfDNA,
      nucleosomes, TNF-alpha, CRP, and IL-6. We did not find any significant
      relationship between the analyzed parameters in either group (i.e., experimental
      or control). Elevated levels of the biomarkers of inflammation (TNF-alpha, CRP,
      and IL-6) and the indicators of apoptosis (cfDNA, circulating nucleosomes) proved
      that exacerbated psoriasis vulgaris is associated with a high degree of systemic
      inflammatory responses and dysregulated apoptotic pathways.

PMID- 29027584
TI  - The Ceratopteris (fern) developing motile gamete walls contain diverse
      polysaccharides, but not pectin.
AB  - MAIN CONCLUSION: Unlike most plant cell walls, the five consecutive walls laid
      down during spermatogenesis in the model fern Ceratopteris contain sparse
      cellulose, lack pectin and are enriched with callose and hemicelluloses. Seed
      free plants like bryophytes and pteridophytes produce swimming male gametes for
      sexual reproduction. During spermatogenesis, unique walls are formed that are
      essential to the appropriate development and maturation of the motile gametes.
      Other than the detection of callose and general wall polysaccharides in scattered
      groups, little is known about the sequence of wall formation and the composition
      of these walls during sperm cell differentiation in plants that produce swimming
      sperm. Using histochemistry and immunogold localizations, we examined the
      distribution of callose, cellulose, mannan and xylan-containing hemicelluloses,
      and homogalacturonan (HG) pectins in the special walls deposited during
      spermatogenesis in Ceratopteris. Five walls are produced in sequence and each has
      a unique fate. The first wall (W1) contains callose and sparse xylan-containing
      hemicelluloses. Wall two (W2) is thin and composed of cellulose crosslinked by
      xylan-containing hemicelluloses. The third wall (W3) is thick and composed
      entirely of callose, and the fourth wall (W4) is built of cellulose heavily
      crosslinked by galactoxyloglucan hemicelluloses. Wall five (W5) is an
      arabinogalactan protein (AGP)-rich matrix in which the gamete changes shape and
      multiple flagella elongate. We detected no esterified or unesterified HG pectins
      in any of the walls laid down during spermatogenesis. To consider evolutionary
      modifications in cell walls associated with motile gametes, comparisons are
      presented with male gametophyte and spermatogenous cell walls across plant
      groups.

PMID- 29027585
TI  - The features of adipose-derived stem cells in patients with inflammatory bowel
      diseases.
AB  - PURPOSE: The treatment outcomes for inflammatory bowel disease (IBD) have been
      improving, but the development of better therapies is needed. Stem cell therapy
      is promising, but little is known about the differences in adipose-derived stem
      cells (ADSCs) between IBD patients and healthy individuals. METHODS: ADSCs were
      isolated from subcutaneous adipose tissue (SAT) in IBD (Crohn's disease, 3;
      ulcerative colitis, 2) and non-IBD (colorectal cancer, 5; breast cancer, 1)
      patients. We also analyzed the effects of tumor necrosis factor (TNF)-alpha on
      murine ADSCs. RESULTS: The numbers of stromal vascular fraction (SVF) cells per
      gram of SAT were 7.72 +/- 3.03 * 105 in IBD and 8.51 +/- 8.80 * 105 in non-IBD
      patients (p > 0.05). The proportions of ADSCs in SVF cells were 4.98 +/- 2.61% in
      IBD and 1.02 +/- 0.67% in non-IBD patients. The numbers of ADSCs per gram of SAT
      were 4.16 +/- 2.96 * 104 in IBD and 0.88 +/- 1.04 * 104 in non-IBD patients. The
      proportions and numbers of ADSCs were significantly higher in IBD patients than
      in non-IBD patients. TNF-alpha significantly facilitated the proliferation and
      motility of murine ADSCs. CONCLUSION: These results showed the potential
      advantage of freshly isolated autologous ADSCs in IBD patients.

PMID- 29027586
TI  - Computational simulation study on ilio-sacral screw fixations for pelvic ring
      injuries and implications in Asian sacrum.
AB  - OBJECTIVES: Despite a high possibility of technique-related complications, ilio
      sacral (IS) screw fixation is the mainstay of operative management in posterior
      pelvic ring injuries. We aimed to make IS screw trajectory with fully
      intraosseous path that was optimal and consistent, and confirm the possibility of
      transiliac-transsacral (TITS) screw fixation in Asian sacrum. METHODS: Eighty-two
      cadaveric sacra (42 males and 40 females) were enrolled and underwent continuous
      1.0-mm slice computed tomography (CT) scans. CT images were imported into
      Mimics(r) software to reconstruct three-dimensional model of the pelvis. To
      simulate IS screws, we inserted 7.0-mm-sized TITS cylinder for first (S1) and
      second (S2) sacral segment and 7.0-mm oblique cylinder for S1. TITS cylinder
      could not be inserted into S1 of 14 models (sacral variation models) but could be
      inserted into the S2 of all models. The actual length of virtual IS screws was
      measured, and anatomic features of safe zone (SZS2) including the area,
      horizontal distance (HDS2), and vertical distance (VDS2) were evaluated by the
      possibility of TITS screw fixation in the S1. RESULTS: When the oblique cylinder
      was directed toward the opposite upper corner of S1 at the level of the first
      foramen, there was no cortical violation regardless of sacral variation. The
      average length of TITS cylinder was 152.3 mm (range 127.9-178.2 mm) in S1 and
      136.0 mm (range 97.8-164.1 mm) in S2, and for oblique cylinder it was 99.2 mm
      (range 82.4-132.2 mm). The average VDS2, HDS2, and the area of SZS2 were 15.5 mm
      (range 8.7-24.4 mm), 18.3 mm (range 12.7-26.6 mm), and 221.1 mm2 (range 91.1
      386.7 mm2), respectively. The VDS2 and SZS2 of sacral variation were
      significantly higher than those of normal (both p = 0.001). CONCLUSIONS:
      Considering the high variability of the S1, it is better to direct the IS screw
      trajectory toward the opposite upper corner of the S1 at the level of first
      sacral foramen. If a TITS screw is needed, the transverse fixation for the S2
      could be performed alternatively due to its sufficient osseous site even in Asian
      sacrum.

PMID- 29027587
TI  - Correlation between endothelial dysfunction and myocardial damage in acute phase
      of Tako-Tsubo cardiomyopathy: brachial flow mediated dilation as a potential
      marker for assessment of patient with Tako-Tsubo.
AB  - Takotsubo cardiomyopathy (TTC) is characterized by transient systolic ventricular
      dysfunction. It is supposed to be caused by a cathecolaminergic wave which leads
      to myocardial stunning through a massive action on beta2-adrenoreceptor.
      Moreover, beta2-receptor hyperactivity negatively influences endothelial
      function. It can be detected by brachial flow mediated dilation (b-FMD) which
      assesses endothelium regulated vasomotility. The study aim is to analyze the b
      FMD variability during hospitalization in 50 patients admitted with TTC. In
      addition, we investigated a possible correlation between b-FMD at admission and
      both length of hospital stay (LOHS) and troponin I peak. We detected b-FMD by
      measuring the hypoxic induced vasoreactivity through assessing brachial artery
      dilation after 5 min of iatrogenic ischemia obtained by inflating a
      sphygmomanometer cuff. Artery diameter modifications were assessed by high
      resolution ultrasound, and a dedicated software calculated accurately the
      percentage of dilation after ischemia by comparing it to the basal. These values
      were measured at admission and on discharge. The obtained values were compared
      for each patient to explore their variability during hospitalization. Moreover,
      the correlation between the b-FMD at admission and both the troponin I peak and
      the LOHS was investigated. There was a statistical significant difference between
      mean FMD measured at admission and at discharge (respectively 1.54 +/- 0.34 and
      8.92 +/- 2.48%; p < 0.001). Moreover, we found a significant negative correlation
      between troponin I peak and FMD values at admission (r = - 0.7645; p < 0.001) and
      a significant inverse correlation between FMD at admission and LOHS (r = -
      0.7543; p < 0.001). There is a significant improvement of b-FMD during
      hospitalization in patients admitted for Tako-Tsubo Cardiomyopathy. Moreover, for
      the first time, a direct correlation among b-FMD, troponin I peak and LOHS has
      been detected.

PMID- 29027588
TI  - Mental disorders and the risk for the subsequent first suicide attempt: results
      of a community study on adolescents and young adults.
AB  - Adolescents and young adults represent the high-risk group for first onset of
      both DSM-IV mental disorders and lifetime suicide attempt (SA). Yet few studies
      have evaluated the temporal association of prior mental disorders and subsequent
      first SA in a young community sample. We examined (a) such associations using a
      broad range of specific DSM-IV mental disorders, (b) the risk of experiencing the
      outcome due to prior comorbidity, and (c) the proportion of SAs that could be
      attributed to prior disorders. During a 10-year prospective study, data were
      gathered from 3021 community subjects, 14-24 years of age at baseline. DSM-IV
      disorders and SA were assessed with the Munich-Composite International Diagnostic
      Interview. Cox models with time-dependent covariates were used to estimate the
      temporal associations of prior mental disorders with subsequent first SA. Most
      prior mental disorders showed elevated risk for subsequent first SA. Highest
      risks were associated with posttraumatic stress disorder (PTSD), dysthymia, and
      nicotine dependence. Comorbidity elevated the risk for subsequent first SA, and
      the more disorders a subject had, the higher the risk for first SA. More than 90%
      of SAs in the exposed group could be attributed to PTSD, and over 30% of SAs in
      the total sample could be attributed to specific phobia. Several DSM-IV disorders
      increase the risk for first SA in adolescents and young adults. Several promising
      early intervention targets were observed, e.g., specific phobia, nicotine
      dependence, dysthymia, and whether a young person is burdened with comorbid
      mental disorders.

PMID- 29027589
TI  - Diagnosis and treatment of severe neurosurgical patients with pyogenic
      ventriculitis caused by gram-negative bacteria.
AB  - The aim of the study is to explore the experiences in diagnosis and treatment of
      severe neurosurgical patients with pyogenic ventriculitis caused by gram-negative
      bacteria (G-). Nineteen patients with pyogenic ventriculitis were reviewed for
      their treatment. The bacterial testing results of cerebrospinal fluid (CSF), the
      clinical intervention, and the patients' prognosis were evaluated. The bacterial
      smears of ventricular drainage from all the cases were G- bacteria. Head CT and
      MRI scans confirmed that they were intraventricular empyema. Eighteen cases of
      CSF bacterial test were positive, including 12 cases of Acinetobacter baumannii
      positive, 2 of Klebsiella pneumonia positive, 2 of Serratia marcescens positive,
      1 of Pseudomonas maltophila positive, and 1 case of Escherichia coli positive.
      One case of the bacterial culture was negative. All patients were treated by
      using intraventricular lavage in combination with intravenous and
      intraventricular antibiotics in accordance with the clinical conditions. After
      treatment for 2 to 8 weeks, 14 patients were cured (74%) and 5 were died (26%).
      Eight patients who were cured had received ventriculoperitoneal shunt due to
      hydrocephalus at 2 to 6 weeks after infection controlled, and none of them had
      any reinfection. Twelve of the 14 cured cases came to consciousness, but 2 were
      persistent in vegetative state starting before the infection; they did not show
      any improving consciousness after infection had been cured. Suppurative
      ventriculitis in severe neurosurgical patients is mainly infected by G- with a
      higher mortality. Early diagnosis, especially in identifying pathogen types,
      timely ventricular irrigation, and ventricular drainage together with intravenous
      and intraventricular antibiotic treatment, should improve prognosis.

PMID- 29027591
TI  - Clinical toxicity of antibody drug conjugates: a meta-analysis of payloads.
AB  - Background Antibody drug conjugates (ADCs) utilize a monoclonal antibody to
      deliver a cytotoxic payload specifically to tumor cells, limiting exposure to
      healthy tissues. Major clinical toxicities of ADCs include hematologic, hepatic,
      neurologic, and ophthalmic events, which are often dose-limiting. These events
      may be off-target effects caused by premature release of payload in circulation.
      A meta-analysis was performed to summarize key clinical safety data for ADCs by
      payload, and data permitting, establish a dose-response model for toxicity
      incidence as a function of payload, dose/regimen, and cancer type. Methods A
      literature search was performed to identify and extract data from clinical ADC
      studies. Toxicity incidence and severity were collected by treatment arm for
      anemia, neutropenia, thrombocytopenia, leukopenia, hepatic toxicity, peripheral
      neuropathy, and ocular toxicity. Exploratory plots, descriptive summaries, and
      logistic regression modelling were used to explore Grade >= 3 (G3/4) toxicities
      and assess the impact of covariates, including cancer type and dose/regimen.
      Results The dataset contained 70 publications; quantitative analysis included 43
      studies with G3/4 toxicity information reported for the endpoints above. G3/4
      anemia, neutropenia and peripheral neuropathy were consistently reported for MMAE
      ADCs, thrombocytopenia and hepatic toxicity for DM1, and ocular toxicity for
      MMAF. Safety profiles of MMAE, DM1, and DM4 ADCs differed between solid and
      hematologic cancers. Conclusions Published ADC clinical data is limited by non
      uniform reporting for toxicity and lack of dosing information, limiting the
      ability to develop quantitative models relating toxicity to exposure. However,
      the current analysis suggests that key G3/4 toxicities of ADCs in the clinic are
      likely off-target and related to payload.

PMID- 29027590
TI  - Diagnostic utility of combined retinal ganglion cell count estimates in Japanese
      glaucoma patients.
AB  - PURPOSE: To assess the combined estimate of retinal ganglion cell (RGC) count
      developed by Medeiros et al. as a tool for diagnosis of glaucoma in Japanese
      patients. STUDY DESIGN: Cross-sectional study. METHODS: Thirty-one eyes of 19
      healthy controls and 106 eyes of 70 glaucoma patients underwent standard
      automated perimetry (SAP) and three types of spectral domain optical coherence
      tomography (SD-OCT) imaging using the Cirrus, RTVue, and 3D-OCT instruments. RGC
      counts derived from SAP and SD-OCT data were estimated using the Harwerth model
      (SAPrgc and OCTrgc, respectively), from which the combined RGC count estimates
      (CRGC) were calculated using the formula developed by Medeiros et al. Receiver
      operating characteristic curve (ROC) analyses were conducted for mean deviation
      (MD), retinal nerve fiber layer thickness (RNFLT), and CRGC. RESULTS: The mean
      OCTrgc derived from the Cirrus, RTVue, and 3D-OCT instruments were 1150, 1245,
      and 1316 (* 1000 cells), respectively, for the control group and 463, 519, and
      516 (* 1000 cells), respectively, for the patient group. SAPrgc of the controls'
      group was 1526 and the patients' group, 731 (* 1000 cells), and were consistently
      greater than OCTrgc in both groups (a generalized estimating equation model, p <
      0.001). Partial area under the curve (pAUC) of MD was 0.178, and that of RNFLT
      and CRGC for the three OCT instruments were 0.185, 0.18, 0.189 and 0.196, 0.196,
      0.197, respectively. CRGC had larger pAUC than MD, whereas there was no or
      marginal difference in pAUC between CRGC and cpRNFLT, irrespective of OCT device
      used or glaucoma severity. CONCLUSION: CRGC proved well suited to discriminate
      glaucoma patients from controls. However, its clinical utility did not seem to
      overwhelm isolated structural measures in the tested Japanese patients.

PMID- 29027592
TI  - A novel citrus viroid found in Australia, tentatively named citrus viroid VII.
AB  - A novel citrus viroid was discovered in a non-symptomatic Lisbon lemon (Citrus x
      limon L. Burm.f.) tree in New South Wales, Australia. Bioindexing, molecular
      detection and characterization involving sequencing combined with in silico
      analysis for the identification of the viroid-RNA hallmark properties of
      transmissibility and autonomous replication as well as specific sequence and
      structural motifs suggest that this viroid is a member of a new species in the
      genus Apscaviroid, family Pospiviroidae, which we have tentatively named "citrus
      viroid VII" (CVd-VII).

PMID- 29027593
TI  - Detecting the effects of coal mining, acid rain, and natural gas extraction in
      Appalachian basin streams in Pennsylvania (USA) through analysis of barium and
      sulfate concentrations.
AB  - To understand how extraction of different energy sources impacts water resources
      requires assessment of how water chemistry has changed in comparison with the
      background values of pristine streams. With such understanding, we can develop
      better water quality standards and ecological interpretations. However,
      determination of pristine background chemistry is difficult in areas with heavy
      human impact. To learn to do this, we compiled a master dataset of sulfate and
      barium concentrations ([SO4], [Ba]) in Pennsylvania (PA, USA) streams from
      publically available sources. These elements were chosen because they can
      represent contamination related to oil/gas and coal, respectively. We applied
      changepoint analysis (i.e., likelihood ratio test) to identify pristine streams,
      which we defined as streams with a low variability in concentrations as measured
      over years. From these pristine streams, we estimated the baseline concentrations
      for major bedrock types in PA. Overall, we found that 48,471 data values are
      available for [SO4] from 1904 to 2014 and 3243 data for [Ba] from 1963 to 2014.
      Statewide [SO4] baseline was estimated to be 15.8 +/- 9.6 mg/L, but values range
      from 12.4 to 26.7 mg/L for different bedrock types. The statewide [Ba] baseline
      is 27.7 +/- 10.6 ug/L and values range from 25.8 to 38.7 ug/L. Results show that
      most increases in [SO4] from the baseline occurred in areas with intensive coal
      mining activities, confirming previous studies. Sulfate inputs from acid rain
      were also documented. Slight increases in [Ba] since 2007 and higher [Ba] in
      areas with higher densities of gas wells when compared to other areas could
      document impacts from shale gas development, the prevalence of basin brines, or
      decreases in acid rain and its coupled effects on [Ba] related to barite
      solubility. The largest impacts on PA stream [Ba] and [SO4] are related to
      releases from coal mining or burning rather than oil and gas development.

PMID- 29027594
TI  - Treatment and survival disparities by ethnicity in New Zealand women with stage I
      III breast cancer tumour subtypes.
AB  - PURPOSE: This study aims to look at the distribution of different subtypes of
      stage I-III breast cancer in Maori and Pacific versus non-Maori/Pacific women,
      and to examine cancer outcomes by ethnicity within these different subtypes.
      METHOD: This study included 9,015 women diagnosed with stage I-III breast cancer
      between June 2000 and May 2013, recorded in the combined Waikato and Auckland
      Breast Cancer Registers, who had complete data on ER, PR and HER2 status. Five
      ER/PR/HER2 subtypes were defined. Kaplan-Meier method and Cox proportional
      hazards model were used to examine ethnic disparities in breast cancer-specific
      survival. RESULTS: Of the 9,015 women, 891 were Maori, 548 were Pacific and 7,576
      others. Both Maori and Pacific women were less likely to have triple negative
      breast cancer compared to others (8.6, 8.9 vs. 13.0%). Pacific women were more
      than twice as likely to have ER-, PR- and HER2+ cancer than Maori and others
      (14.2 vs. 6.0%, 6.7%). After adjustment for age, year of diagnosis, stage, grade
      and treatment, the hazard ratios of breast cancer-specific mortality for Maori
      and Pacific women with ER+, PR+ and HER2- were 1.52 (95% CI 1.06-2.18) and 1.55
      (95% CI 1.04-2.31) compared to others, respectively. Maori women with HER2+
      cancer were twice more likely to die of their cancer than others. CONCLUSIONS:
      Outcomes for Maori and Pacific women could be improved by better treatment
      regimens especially for those with HER2+ breast cancer and for women with ER+,
      PR+ and HER2- breast cancer.

PMID- 29027596
TI  - 10-year parasitological examination results (2003 to 2012) of faecal samples from
      horses, ruminants, pigs, dogs, cats, rabbits and hedgehogs.
AB  - The results of coproscopical examinations in domestic animals and hedgehogs
      carried out as routine diagnostics in the years 2003 to 2012 at the Institute for
      Parasitology, University of Veterinary Medicine Hannover, Germany, are presented.
      Of 3475 horse faecal samples, 30.1% contained stages of strongyles and 1.3% eggs
      of Strongyloides westeri and Parascaris equorum, respectively. The most
      frequently observed parasite stages in 1416 cattle faecal samples were Eimeria
      oocysts (21.3%) and strongyle eggs or larvae (15.9%). Dictyocaulus viviparus
      larvae and Fasciola hepatica eggs were identified in 0.9 and 1.3% of samples. Of
      574 bovine faecal samples analysed by carbol-fuchsin staining, 39.9% were
      positive for Cryptosporidium oocysts. Stages of strongyles were found in 52.4% of
      sheep (n = 374) and 44.9% of goat faeces (n = 98) and Eimeria oocysts in 41.4 and
      32.7% of their faeces, respectively. Of 1848 pig faecal samples, 3.0% contained
      stages of strongyles, 1.6% eggs of Ascaris suum and 3.3% coccidian (Eimeria or
      Cystoisospora spp.) oocysts. The most frequently detected helminth eggs in faecal
      samples of dogs (n = 2731) and cats (n = 903) were Toxocara spp. (2.8 and 3.9%,
      respectively). Cystoisospora oocysts were identified in 5.6% of dog and 2.4% of
      cat faeces. Furthermore, 0.7% of the cat samples were positive for small
      Toxoplasma gondii-like oocysts. The faecal samples of rabbits (n = 434) contained
      eggs of Passalurus ambiguus (3.0%), strongyles (1.8%) and Trichuris leporis
      (0.2%) as well as Eimeria oocysts (21.2%). The most abundant nematodes in the
      samples of hedgehogs (n = 205) were Capillaria spp. (39.5%) and Crenosoma
      striatum (26.8%); coccidian oocysts were found in 14.2% of the samples.

PMID- 29027595
TI  - Carnosinase, diabetes mellitus and the potential relevance of carnosinase
      deficiency.
AB  - Carnosinase (CN1) is a dipeptidase, encoded by the CNDP1 gene, that degrades
      histidine-containing dipeptides, such as carnosine, anserine and homocarnosine.
      Loss of CN1 function (also called carnosinase deficiency or aminoacyl-histidine
      dipeptidase deficiency) has been reported in a small number of patients with
      highly elevated blood carnosine concentrations, denoted carnosinaemia; it is
      unclear whether the variety of clinical symptoms in these individuals is causally
      related to carnosinase deficiency. Reduced CN1 function should increase serum
      carnosine concentrations but the genetic basis of carnosinaemia has not been
      formally confirmed to be due to CNDP1 mutations. A CNDP1 polymorphism associated
      with low CN1 activity correlates with significantly reduced risk for diabetic
      nephropathy, especially in women with type 2 diabetes, and may slow progression
      of chronic kidney disease in children with glomerulonephritis. Studies in rodents
      demonstrate antiproteinuric and vasculoprotective effects of carnosine, the
      precise molecular mechanisms, however, are still incompletely understood. Thus,
      carnosinemia due to CN1 deficiency may be a non-disease; in contrast, carnosine
      may potentially protect against long-term sequelae of reactive metabolites
      accumulating, e.g. in diabetes and chronic renal failure.

PMID- 29027598
TI  - A randomized phase II study of weekly paclitaxel with or without pelareorep in
      patients with metastatic breast cancer: final analysis of Canadian Cancer Trials
      Group IND.213.
AB  - BACKGROUND: Pelareorep, a serotype 3 reovirus, has demonstrated preclinical and
      early clinical activity in breast cancer and synergistic cytotoxic activity with
      microtubule targeting agents. This multicentre, randomized, phase II trial was
      undertaken to evaluate the efficacy and safety of adding pelareorep to paclitaxel
      for patients with metastatic breast cancer (mBC). METHODS: Following a safety run
      in of 7 patients, 74 women with previously treated mBC were randomized either to
      paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 every 4 weeks plus
      pelareorep 3 * 1010 TCID50 intravenously on days 1, 2, 8, 9, 15, and 16 every 4
      weeks (Arm A) or to paclitaxel alone (Arm B). Primary endpoint was progression
      free survival (PFS). Secondary endpoints were objective response rate, overall
      survival (OS), circulating tumour cell counts, safety, and exploratory
      correlative analyses. All comparisons used a two-sided test at an alpha level of
      20%. Survival analyses were adjusted for prior paclitaxel. RESULTS: Final
      analysis was performed after a median follow-up of 29.5 months. Pelareorep was
      well tolerated. Patients in Arm A had more favourable baseline prognostic
      variables. Median adjusted PFS (Arm A vs B) was 3.78 mo vs 3.38 mo (HR 1.04, 80%
      CI 0.76-1.43, P = 0.87). There was no difference in response rate between arms (P
      = 0.87). Median OS (Arm A vs B) was 17.4 mo vs 10.4 mo (HR 0.65, 80% CI 0.46
      0.91, P = 0.1). CONCLUSIONS: This first, phase II, randomized study of pelareorep
      and paclitaxel in previously treated mBC did not show a difference in PFS (the
      primary endpoint) or RR. However, there was a significantly longer OS for the
      combination. Further exploration of this regimen in mBC may be of interest.

PMID- 29027597
TI  - Lipoprotein-associated phospholipase A2 activity in obese adolescents with and
      without type 2 diabetes.
AB  - Lipoprotein-associated phospholipase A2 (Lp-PLA2) was identified as a strong
      predictor for cardiovascular events. Furthermore, it is highly associated with
      obesity. The role of Lp-PLA2 in diabetes mellitus is controversial and analyses,
      especially in adolescents with type 2 diabetes (T2D), are missing. Therefore, we
      compared Lp-PLA2 activity between two obese age-, sex-, and BMI-matched cohorts
      of adolescents with and without T2D. Relationships between Lp-PLA2 activity and
      age, BMI, hemoglobin A1c, lipids, and adipokines were evaluated. Lp-PLA2 activity
      was analyzed in serum of 72 obese adolescents without T2D (mean age 15.2 +/- 1.6
      years) and in 65 obese adolescents with T2D (mean age 15.5 +/- 1.8 years).
      Clinical data were obtained from the Diabetes-Patienten-Verlaufsdokumentation
      (DPV) registry. Surprisingly, obese adolescents with T2D had lower levels of Lp
      PLA2 activity than obese children without T2D (160.2 +/- 45.0 versus 180.9 +/-
      35.6 nmol/min/ml, p = 0.003), but this decrease could only be detected in male
      (158.8 +/- 45.3 versus 190.8 +/- 31.3 nmol/min/ml, p < 0.001) and not in female
      adolescents (162.1 +/- 45.5 versus 167.7 +/- 37.1 nmol/min/ml, p = 0.60). In
      multiple linear regression analysis, differences in Lp-PLA2 activity between
      cohorts remained large and significant (beta-coefficient: -31.60, 95% confidence
      interval [-49.27;-13.93], p < 0.001). Furthermore, Lp-PLA2 activity was
      positively associated with BMI (beta-coefficient: 2.04 [0.68;3.40], p = 0.004)
      and negatively associated with the adipokines leptin (beta-coefficient: -0.53 [
      0.89;-0.17], p = 0.004) and adiponectin (beta-coefficient: -3.06, [-5.63;-0.48],
      p = 0.02). Elevated mean glucose concentrations in adolescents with T2D were not
      associated with an increase but with a decrease of Lp-PLA2 activity. Hence, in
      young patients with T2D the Lp-PLA2 activity as a risk predictor for
      cardiovascular events needs further investigation.

PMID- 29027600
TI  - Improved hydrolase activity in barley and reduced malting time by adding phytase
      as an activator during malting steeping.
AB  - OBJECTIVES: Exogenous phytase improved the activity of hydrolases to decrease the
      malting time. RESULTS: Treatment with phytase during barley steeping increased
      activity of hydrolases (alpha-/beta-amylase, proteinase, beta-glucanase and
      xylanase) in green malt. Maximal activity was observed for alpha-/beta-amylase,
      beta-glucanase and xylanase with 0.8 U phytase/g and proteinase with 1.2 U
      phytase/g. Phytase promoted acrospire growth of green malt and reduced malting
      process with 0.8 U phytase/g in 96 h, which is 24 h less than the control. No
      significant variation of malt quality was found between control malt and malt
      treated with 0.8 U/g or 1.2 U phytase/g (P > 0.05), which makes application of
      exogenous phytase during steeping process as a good option for reducing malting
      time. CONCLUSION: Adding phytase during steeping process increases the activity
      of hydrolases, which reduces malting time without impacting on malt quality.

PMID- 29027599
TI  - Dyspepsia, Diarrhea, and Deafness: Some Calling Cards of the Great Mimic!

PMID- 29027601
TI  - DNMT1, DNMT3A and DNMT3B proteins are differently expressed in mouse oocytes and
      early embryos.
AB  - DNA methylation is one of the epigenetic mechanisms and plays important roles
      during oogenesis and early embryo development in mammals. DNA methylation is
      basically known as adding a methyl group to the fifth carbon atom of cytosine
      residues within cytosine-phosphate-guanine (CpG) and non-CpG dinucleotide sites.
      This mechanism is composed of two main processes: de novo methylation and
      maintenance methylation, both of which are catalyzed by specific DNA
      methyltransferase (DNMT) enzymes. To date, six different DNMTs have been
      characterized in mammals defined as DNMT1, DNMT2, DNMT3A, DNMT3B, DNMT3C, and
      DNMT3L. While DNMT1 primarily functions in maintenance methylation, both DNMT3A
      and DNMT3B are essentially responsible for de novo methylation. As is known,
      either maintenance or de novo methylation processes appears during oocyte and
      early embryo development terms. The aim of the present study is to investigate
      spatial and temporal expression levels and subcellular localizations of the
      DNMT1, DNMT3A, and DNMT3B proteins in the mouse germinal vesicle (GV) and
      metaphase II (MII) oocytes, and early embryos from 1-cell to blastocyst stages.
      We found that there are remarkable differences in the expressional levels and
      subcellular localizations of the DNMT1, DNMT3A and DNMT3B proteins in the GV and
      MII oocytes, and 1-cell, 2-cell, 4-cell, 8-cell, morula, and blastocyst stage
      embryos. The fluctuations in the expression of DNMT proteins in the analyzed
      oocytes and early embryos are largely compatible with DNA methylation changes and
      genomic imprintestablishment appearing during oogenesis and early embryo
      development. To understand precisemolecular biological meaning of differently
      expressing DNMTs in the early developmental periods, further studies are
      required.

PMID- 29027603
TI  - Review of people with retinal vasculitis and positive QuantiFERON(r)-TB Gold test
      in an area nonendemic for tuberculosis.
AB  - PURPOSE: To assess the frequency of a positive QuantiFERON(r)-TB Gold test
      (quantiferon) among patients with retinal vasculitis in an area nonendemic for
      tuberculosis (TB); to review clinical characteristics and management of affected
      individuals. METHODS: Consecutive patients with retinal vasculitis and a positive
      quantiferon were retrospectively analyzed. Demographics, clinical data,
      laboratory, imaging findings, and therapy were evaluated. RESULTS: Among 49
      patients with retinal vasculitis, 12 (24%) had a positive quantiferon. Median age
      was 37 years, there were five female patients. Five individuals (42%) had
      previously lived in a country endemic for TB. Retinal vasculitis was occlusive in
      six patients (50%). On chest imaging, pulmonary tuberculosis was suspected in one
      patient (8.3%). Treatment modalities included full antitubercular treatment (n =
      1), isoniazid prophylaxis (n = 6), systemic corticosteroids (n = 8), and laser
      treatment (n = 5). After a median follow-up of 27.5 months, inflammation was
      inactive (n = 6) or recurrently present (n = 6). No patient lost >= 2 lines of
      best-corrected visual acuity during follow-up. CONCLUSIONS: The quantiferon test
      is recommended in the evaluation of people with retinal vasculitis.
      Interpretation of a positive result can be challenging in a country nonendemic
      for TB. The majority of patients with quantiferon-positive retinal vasculitis
      were found to have latent TB.

PMID- 29027602
TI  - Combining risk communication strategies to simultaneously convey the risks of
      four diseases associated with physical inactivity to socio-demographically
      diverse populations.
AB  - A single risk factor can increase the risk of developing multiple diseases, but
      most risk communication research has been conducted in the context of a single
      disease. We explored which combination of three recommended risk communication
      strategies is most effective in simultaneously conveying risk estimates of four
      diseases associated with physical inactivity: colon cancer, stroke, diabetes, and
      heart disease. Participants (N = 1161, 50% no college experience, 50%
      racial/ethnic minority) were shown hypothetical risk estimates for each of the
      four diseases. All four diseases were placed at varying heights on 1 of 12
      vertical bar charts (i.e., "risk ladders") to indicate their respective
      probabilities. The risk ladders varied in a 2 (risk reduction information:
      present/absent) * 2 (numerical format: words/words and numbers) * 3 (social
      comparison information: none/somewhat higher than average/much higher than
      average) full factorial design. Participants were randomly assigned to view one
      of the risk ladders and then completed a questionnaire assessing message
      comprehension, message acceptance, physical activity-related risk and efficacy
      beliefs, and physical activity intentions. Higher message acceptance was found
      among (1) people who received risk reduction information versus those who did not
      (p = .01), and (2) people who did not receive social comparison information
      versus those told that they were at higher than average risk (p = .03). Further,
      absolute cognitive perceived risk of developing "any of the diseases shown in the
      picture" was higher among people who did not receive social comparison
      information (p = .03). No other main effects and only very few interactions with
      demographic variables were found. Combining recommended risk communication
      strategies did not improve or impair key cognitive or affective precursors of
      health behavior change. It might not be necessary to provide people with
      extensive information when communicating risk estimates of multiple diseases.

PMID- 29027604
TI  - Prevalence of avian influenza (H9N2) in commercial quail, partridge, and turkey
      farms in Iran, 2014-2015.
AB  - Avian influenza virus (AIV) H9N2 subtype is endemic in Iran and causes
      substantial economic loss to the growing poultry industry within the country. In
      this study, a cross-sectional analysis was carried out to determine the sero
      prevalence of H9N2 in several commercial farms between the years 2014 and 2015.
      The comparison of the mean of serum titers and the ratio of sero-positive birds
      between all units were analyzed using one-way ANOVA test. In 2014, a total of 77
      farms (58 turkey farms, 14 quail farms, and 5 partridge farms) and 894 birds (682
      turkeys, 154 quails, and 58 partridges) were sampled while in 2015, a total of 69
      farms (54 turkey farms, 8 quail farms, and 7 partridge farms) and 856 birds (675
      turkeys, 105 quails, and 76 partridges) were sampled. Of that, 52 of 77 sampled
      farms (67.5%) and 437 of 894 samples (48.9%) were positive for H9N2 in 2014
      while. Forty-one of 69 farms (59.4%) and 307 of 856 sera (35.9%) were positive in
      2015. Furthermore, the mean titer of partridge farms was significantly lower than
      that of turkey farms (p < 0.01) and the mean percentage of sero-positive turkey
      farms was significantly higher than partridge farms (p < 0.01) in 2014. In 2015,
      no significant difference was observed between the mean sera titer amongst farms
      and percentage of sero-positive birds (p > 0.05). Our results indicated that H9N2
      is circulating in these farms. Since many more such farms are being established
      for operations, in addition to the threat of emergence and continuous reemergence
      of the disease in these farms, enhanced veterinary biosecurity measures on farms
      are required for mitigation.

PMID- 29027605
TI  - Short-term depression and transient memory in sensory cortex.
AB  - Persistent neuronal activity is usually studied in the context of short-term
      memory localized in central cortical areas. Recent studies show that early
      sensory areas also can have persistent representations of stimuli which emerge
      quickly (over tens of milliseconds) and decay slowly (over seconds). Traditional
      positive feedback models cannot explain sensory persistence for at least two
      reasons: (i) They show attractor dynamics, with transient perturbations resulting
      in a quasi-permanent change of system state, whereas sensory systems return to
      the original state after a transient. (ii) As we show, those positive feedback
      models which decay to baseline lose their persistence when their recurrent
      connections are subject to short-term depression, a common property of excitatory
      connections in early sensory areas. Dual time constant network behavior has also
      been implemented by nonlinear afferents producing a large transient input
      followed by much smaller steady state input. We show that such networks require
      unphysiologically large onset transients to produce the rise and decay observed
      in sensory areas. Our study explores how memory and persistence can be
      implemented in another model class, derivative feedback networks. We show that
      these networks can operate with two vastly different time courses, changing their
      state quickly when new information is coming in but retaining it for a long time,
      and that these capabilities are robust to short-term depression. Specifically,
      derivative feedback networks with short-term depression that acts differentially
      on positive and negative feedback projections are capable of dynamically changing
      their time constant, thus allowing fast onset and slow decay of responses without
      requiring unrealistically large input transients.

PMID- 29027606
TI  - Positive and Negative Peer Influence in Residential Care.
AB  - The potential for negative peer influence has been well established in research,
      and there is a growing interest in how positive peer influence also impacts
      youth. No research, however, has concurrently examined positive and negative peer
      influence in the context of residential care. Clinical records for 886
      residential care youth were used in a Hierarchical Linear Model analysis to
      examine the impact of negative and positive peer influence on naturally occurring
      patterns of serious problem behavior over time. Negative peer influence, where
      the majority of youth in a home manifested above the average number of serious
      behavior problems, occurred 13.7% of the time. Positive peer influence, where the
      majority of youth manifested no serious problem behaviors for the month, occurred
      47.7% of the time. Overall, youth problem behavior improved over time. There were
      significantly lower rates of serious problem behavior in target youth during
      positive peer influence months. Conversely, there were significantly higher rates
      of serious problem behaviors in target youth during negative peer influence
      months. Negative peer influence had a relatively greater impact on target peers'
      serious behavior problems than did positive peer influence. Caregiver experience
      significantly reduced the impact of negative peer influence, but did not
      significantly augment positive peer influence. Months where negative peer
      influence was combined with inexperienced caregivers produced the highest rates
      of serious problem behavior. Our results support the view that residential
      programs for troubled youth need to create circumstances that promote positive
      and control for negative peer influence.

PMID- 29027608
TI  - Ivabradine in Postural Orthostatic Tachycardia Syndrome: Preliminary Experience
      in Children.
AB  - OBJECTIVE: Ivabradine is a selective and specific inhibitor of the I(f) current
      in the sinoatrial and atrioventricular nodes. It decreases heart rate and
      myocardial oxygen consumption at rest and during exercise. It is used in adults
      for management of heart failure and angina, but promising results have been
      obtained in postural orthostatic tachycardia syndrome (POTS). There is little
      experience of ivabradine in childhood, although it is used on a compassionate
      basis. Our aim was to review our experience of ivabradine in a retrospective
      evaluation of pediatric patients with POTS. METHODS: We evaluated all patients
      younger than 18 years for whom ivabradine had been prescribed for this
      indication, from February 2008 to June 2014. RESULTS: Twenty-two patients were
      identified (15 female). Median age was 14.5 years (11-17 years). The ivabradine
      dosage after up-titration was 0.1 mg/kg per dose twice daily. In 15 (68%)
      symptoms improved. Ivabradine was suspended in five, but only in one for
      worsening of symptoms. There was a reduction in heart rate on resting
      electrocardiogram (EKG) from a mean (standard deviation) of 82.5 (13.6) bpm to a
      mean of 71 (16.5) bpm (p = 0.007). No patient had increased duration of QTc (p =
      0.44). One (4.5%) experienced phosphenes. CONCLUSIONS: From this initial
      experience, ivabradine is safe in patients younger than 18 years with POTS. We
      observed improvement of symptoms in 68% and phosphenes in less than 5%. Further
      studies are needed to assess the safety in a randomized control setting.

PMID- 29027607
TI  - Developing a patient-reported outcome measure for HIV care on perceived barriers
      to antiretroviral adherence: assessing the needs of HIV clinicians through
      qualitative analysis.
AB  - PURPOSE: To identify HIV clinicians' needs for the clinical use of a new patient
      reported outcome measure (PRO) on barriers to antiretroviral therapy (ART)
      adherence. METHODS: In 2015, five focus groups with 31 clinicians from France
      were transcribed, coded with Atlas.ti, and submitted to a typological analysis.
      RESULTS: The analysis identified seven patient profiles, each tied to distinct
      barriers to adherence and to specific needs for the PRO's content, data
      collection and transmission. Clinicians preferred, for the patient who is: (1)
      'passive,' that the PRO collect information on ART knowledge, to ensure that the
      prescription's instructions are being respected; (2) 'misleading,' that it be
      able to detect adherence to ART and socially desirable responses; (3) 'stoic,'
      that questions challenge the patient to recognize treatment-specific side
      effects; (4) 'hedonistic,' that the PRO contains content on lifestyle and risk
      taking; (5) 'obsessive,' that the PRO captures quality of life and stressful life
      events; (6) 'overburdened,' that the PRO provides information on the person's
      home environment, socioeconomic status and cultural constraints. For all or most
      patient profiles, the clinicians wished that the PRO be completed, minimally,
      prior to the medical consultation and to receive alerts, under varying
      conditions, when problematic scores were detected. Depending on the profile,
      there was preference for the inclusion of open-ended questions and transmission
      of cross-sectional, periodic or longitudinal PRO data. CONCLUSION: Overall, this
      study's findings suggest that to support the clinical management of ART
      adherence, our PRO must meet the needs of a wide variety of patients and must
      perform multiple functions.

PMID- 29027609
TI  - Juvenile Trabecular Ossifying Fibroma.
AB  - Benign fibro-osseous lesions within the maxillofacial region represent a
      heterogeneous group of benign entities with overlapping histologic features.
      Ossifying fibroma, the rarest of these entities, represents a true neoplasm.
      Juvenile ossifying fibroma (JOF) is considered an aggressive rapidly growing sub
      type. It tends to occur in the first or second decades of life. Based on
      histological and clinical features it can further be classified into two
      variants, namely juvenile trabecular ossifying fibroma (JTOF) and juvenile
      psammomatoid ossifying fibroma (JPOF). JTOF features a proliferation of cellular
      fibroblastic tissue admixed with woven bone trabeculae with varying histologic
      presentations. Correlation with clinical and radiographic features is essential
      to differentiate it from other fibro-osseous lesions. A case of JTOF of the
      mandible is exemplified in this Sine Qua Non Radiology-Pathology article.

PMID- 29027610
TI  - Risk Factors for and Incidence of Seizures in Metastatic Castration-Resistant
      Prostate Cancer: A Real-World Retrospective Cohort Study.
AB  - BACKGROUND AND OBJECTIVE: This real-world study assessed the prevalence, risk
      factors for, and incidence of seizures in patients with metastatic castration
      resistant prostate cancer (mCRPC). METHODS: Patients with mCRPC were selected
      from MarketScan Commercial and Medicare Supplemental Databases between 1 January
      2009 and 31 July 2012. Prevalence of seizure risk factors were described
      separately and in combination with other risk factors. Seizure incidence was
      calculated overall and for each risk factor group. RESULTS: The most common risk
      factors were history of seizure threshold-lowering medication use (35%), history
      of loss of consciousness (6%), history of transient ischemic attack or
      cerebrovascular accident (2%), treated brain metastasis (0.9%), history of
      seizure (0.6%), and dementia (0.5%). Overall, seizure incidence was 1.8 per 100
      person-years (PYs) (95% confidence interval [CI] 1.5-2.1), being higher among
      patients with at least one risk factor (2.8 per 100 PYs; 95% CI 2.2-3.4) than
      those without risk factors (1.2 per 100 PYs; 95% CI 1.0-1.6). Seizure incidence
      was highest among a few patients (0.6%) with a history of seizure (82.0 per 100
      PYs; 95% CI 45.9-135.2) and within this small subpopulation, higher among those
      with a history of anticonvulsant use (120.9 per 100 PYs; 95% CI 60.3-216.3) than
      without anticonvulsant use (43.5 per 100 PYs; 95% CI 11.9-111.3). CONCLUSION:
      History of seizure is an important risk factor for seizure occurrence in patients
      with mCRPC, particularly in those with a history of anticonvulsant use. These
      findings improve understanding of the risk of seizure occurrence in patients with
      mCRPC, who are potential users of androgen receptor antagonists, including
      enzalutamide.

PMID- 29027611
TI  - Preparation of flexible bone tissue scaffold utilizing sea urchin test and
      collagen.
AB  - Gonads of sea urchin are consumed in Japan and some countries as food and most
      parts including its tests are discarded as marine wastes. Therefore, utilization
      of them as functional materials would reduce the waste as well as encourage
      Japanese fishery. In this study, magnesium containing calcite granules collected
      from sea urchin tests were hydrothermally phosphatized and the obtained granules
      were identified as approximately 82% in mass of magnesium containing beta
      tricalcium phosphate and 18% in mass of nonstoichiometric hydroxyapatite, i.e., a
      biphasic calcium phosphate, maintaining the original porous network. Shape
      controlled scaffolds were fabricated with the obtained biphasic calcium phosphate
      granules and collagen. The scaffolds showed good open porosity (83.84%) and
      adequate mechanical properties for handling during cell culture and subsequent
      operations. The MG-63 cells showed higher proliferation and osteogenic
      differentiation in comparison to a control material, the collagen sponge with the
      same size. Furthermore, cell viability assay proved that the scaffolds were not
      cytotoxic. These results suggest that scaffold prepared using sea urchin test
      derived calcium phosphate and collagen could be a potential candidate of bone
      void fillers for non-load bearing defects in bone reconstruction as well as
      scaffolds for bone tissue engineering.

PMID- 29027612
TI  - Penetrance of a rare familial mutation predisposing to papillary thyroid cancer.
AB  - Familial non-medullary thyroid cancer (FNMTC) is clinically defined as two or
      more first-degree relatives with NMTC and appears to follow an autosomal dominant
      inheritance pattern. Approximately 5-7% of NMTC is hereditary and affects
      multiple generations with a young age of onset. The primary aim of this study was
      to determine the age-specific penetrance of NMTC in individuals from a large
      family with FNMTC with a previously identified private mutation at 4q32, with a
      secondary aim to determine the penetrance for benign thyroid disease in this
      family. We present a large family with NMTC in which we had previously described
      a culpable mutation. Participants provided their personal medical history and
      family history. The germline 4q32 A > C mutation was detected in 34 of 68 tested
      individuals. Age-specific penetrance of thyroid cancer and benign thyroid disease
      was determined using the inverted Kaplan-Meier method of segregation analysis.
      Individuals who tested positive for the 4q32 mutation have a 68.9% (95% CI 46.5
      88.7) risk of developing thyroid cancer by age 70 and a 65.3% (95% CI 46.0-83.8)
      risk of developing benign thyroid disease by age 70. The 4q32 A > C mutation
      significantly increases the risk to develop thyroid cancer but not benign thyroid
      disease in members of this family. The female:male sex ratio of 1.33 that we
      observed in affected mutation carriers differs greatly from the ratio of
      approximately 3:1 observed in PTC, supporting a central role of the mutation.
      Early thyroid surveillance with annual ultrasound is recommended to individuals
      testing positive for this private familial mutation.

PMID- 29027613
TI  - Both decreased Akt expression and mTOR phosphorylation are related to decreased
      neuronal differentiation in the hippocampal alveus of aged mice.
AB  - BACKGROUND: Aging is an inevitable process which results in many changes. These
      changes are closely related to the hippocampus which is in charge of long-term
      learning and episodic memory. AIM: This study was to investigate age-related
      changes of the cell proliferation, neuroblast differentiation and Akt/mTOR
      signaling in the hippocampal alveus of aged mice. METHODS: In the present study,
      we compared the differences of neurogenesis in the hippocampal alveus between
      adult (postnatal month 6) and aged (postnatal month 24) mice using
      immunohistochemistry and western blot analysis. RESULTS: The cell proliferation,
      neuroblast differentiation, and the increased astrocyte activation in the
      hippocampal alveus of mice were decreased in an age-dependent manner. In
      addition, during normal aging, the protein level of AKT, mTOR and the
      phosphorylation of mTOR were all decreased. However, the protein level of AKT was
      increased. DISCUSSION: These results indicate the neurogenesis in the immature
      neurons in the hippocampal alveus of aged mice was closely related to the normal
      aging process. In addition, during normal aging, the increased AKT
      phosphorylation and decreased mTOR phosphorylation in the hippocampus may play a
      role in aging development. CONCLUSION: The result indicates that increased
      activation of astrocyte, increased phosphorylation of AKT and decreased
      phosphorylation of mTOR may be involved in the decreased cell proliferation and
      neuroblast differentiation in the alveus of hippocampus of aged mice.

PMID- 29027614
TI  - Statistical crossover and nonextensive behavior of neuronal short-term
      depression.
AB  - The theoretical basis of neuronal coding, associated with short-term degradation
      in synaptic transmission, is a matter of debate in the literature. In fact,
      electrophysiological signals are commonly characterized as inversely proportional
      to stimulus intensity. Among theoretical descriptions of this phenomenon, models
      based on 1/f-dependency are employed to investigate the biophysical properties of
      short-term synaptic depression. In this work, we formulate a model based on a
      paradigmatic q-differential equation to obtain a generalized formalism useful for
      investigation of nonextensivity in this specific type of synaptic plasticity. Our
      analysis reveals nonextensivity in data from electrophysiological recordings and
      also a statistical crossover in neurotransmission. In particular, statistical
      transitions provide additional support to the hypothesis of heterogeneous release
      probability of neurotransmitters. On the other hand, the simple vesicle model
      agrees with data only at low-frequency stimulations. Thus, the present work
      presents a method to demonstrate that short-term depression is not only governed
      by random mechanisms but also by nonextensive behavior. Our findings also
      conciliate morphological and electrophysiological investigations into a coherent
      biophysical scenario.

PMID- 29027615
TI  - Assessment of the Role of Everolimus Therapy in Patients with Renal Cell
      Carcinoma Based on Daily Routine and Recent Research Results.
AB  - Everolimus is indicated for adults with metastatic renal cell carcinoma (mRCC)
      after failure of vascular endothelial growth factor receptor-tyrosine kinase
      inhibitors (TKI). Currently, the therapeutic applicability of EVE has been
      changing. Multicenter evaluation of efficacy and safety of everolimus in daily
      routine and definition of patient characteristics with favorable outcome. Data of
      165 patients from 9 oncology institutes in Hungary were analyzed retrospectively.
      Everolimus therapy was used after one TKI in 10 mg starting dose. Physical and
      laboratory examinations and imaging tests were performed monthly and every 3
      months, respectively. Median progression-free survival (PFS) was 5.4 months.
      Median overall survival (OS) was 16.2 months. PFS and OS results were more
      favorable in patients with ECOG 0-1 (p PFS  = 0.033, p OS  = 0.008) and after >9
      months of TKI therapy (p PFS  = 0.019, p OS  = 0.045). Survival was longer in
      nonanemic patients with ECOG 0-1 than in anemic patients with ECOG 2-3, 30.9 and
      7.7 months, respectively (p = 0.029). Dose reduction and treatment delay was
      required in 6.2% and 8.9% of patients, respectively. Common adverse events were
      exanthema, edema, stomatitis, anemia, and abnormal kidney functions and glucose
      levels. Results of this study show that everolimus is safe and efficacious in a
      real-world setting. Everyday practice showed that nonanemic patients with good
      performance status receiving TKI therapy for >9 months are favorable candidates
      for this treatment. Despite the efficiency of novel, registered drugs, everolimus
      still plays an important role during and after second-line therapy for mRCC when
      availability of modern remedies is limited.

PMID- 29027616
TI  - Hormone receptor-positive invasive lobular and ductal carcinoma of the breast
      have comparable hormone receptor expression levels both if detected by screening
      and clinically.

PMID- 29027617
TI  - Zebrafish as a model to study neuroblastoma development.
AB  - Neuroblastoma is a pediatric solid tumor arising from embryonic neural crest
      progenitor cells that normally generate the peripheral sympathetic nervous
      system. As such, the location of neuroblastoma tumors is correlated with the
      distribution of major post-ganglionic clusters throughout the sympathetic chain,
      with the highest incidence in the adrenal medulla or lumbar sympathetic ganglia
      (~65%). Neuroblastoma is an enigmatic tumor that can spontaneously regress with
      minimal treatment or become highly metastatic and develop resistance to
      aggressive treatments, including radiation and high-dose chemotherapy. Age of
      diagnosis, stage of disease and cellular and genetic features often predict
      whether the tumor will regress or advance to metastatic disease. Recent efforts
      using molecular and genomic technologies have allowed more accurate
      stratification of patients into low-, intermediate- and high-risk categories,
      thereby allowing for minimal intervention in low-risk patients and providing
      potential new therapeutic targets, such as the ALK receptor tyrosine kinase, for
      high-risk or relapsed patients. Despite these advances, the overall survival of
      high-risk neuroblastoma patients is still less than 50%. Furthermore, next
      generation sequencing has revealed that almost two-thirds of neuroblastoma tumors
      do not contain obvious pathogenic mutations, suggesting that epigenetic
      mechanisms and/or a perturbed cellular microenvironment may heavily influence
      neuroblastoma development. Understanding the mechanisms that drive neuroblastoma,
      therefore, will likely require a combination of genomic, developmental and cancer
      biology approaches in whole animal systems. In this review, we discuss the
      contributions of zebrafish research to our understanding of neuroblastoma
      pathogenesis as well as the potential for this model system to accelerate the
      identification of more effective therapies for high-risk neuroblastoma patients
      in the future.

PMID- 29027618
TI  - Moral Injury: Contextualized Care.
AB  - Amidst the return of military personnel from post-9/11 conflicts, a construct
      describing the readjustment challenges of some has received increasing attention:
      moral injury. This term has been variably defined with mental health
      professionals more recently conceiving of it as a transgression of moral beliefs
      and expectations that are witnessed, perpetrated, or allowed by the individual.
      To the extent that morality is a system of conceptualizing right and wrong,
      individuals' moral systems are in large measure developmentally and socially
      derived and interpreted. Thus, in seeking to provide care and aid in
      reintegration for combat veterans, it is necessary to consider communities that
      have contributed to an individual's formation and that might have participated in
      the interpretation of his/her suffering. This can take many forms, but given that
      morality is often complexly intertwined with issues of religion, faith, and
      spirituality for many individuals, and recognizing that much of the current focus
      on moral injury is emanating out of healthcare contexts, we devote particular
      attention to how chaplains might be more intentionally engaged in healthcare
      systems such as the Veterans Health Administration to provide non-judgmental,
      person-centered, culturally-relevant care rooted in communities of practice to
      veterans with moral injury.

PMID- 29027619
TI  - "Even Heroes Get Depressed": Sponsorship and Self-Stigma in Canada's Mental
      Illness Awareness Week.
AB  - In 1992, the Canadian Psychiatric Association launched Canada's first national
      campaign against mental illness, Mental Illness Awareness Week (MIAW). I stress
      that pharmaceutical sponsorship of the first five years of MIAW (1992-1997) was
      integral to shaping the trajectory of the campaign and marks a shift in the way
      stigma is conceived and resisted in Canada: what was an interpersonal process
      based on social norms becomes refigured as "self-stigma," or an individualized
      process in which lack of information, education, and self-assessment contribute
      to an inability to consider oneself as at-risk for a disease, condition, or
      disorder.

PMID- 29027620
TI  - Evaluation of the tolerability and efficacy of sodium polystyrene sulfonate for
      long-term management of hyperkalemia in patients with chronic kidney disease.
AB  - PURPOSE: Sodium polystyrene sulfonate (SPS) is a cation-exchanging resin that has
      been widely used for several decades as first-line therapy of mild chronic
      hyperkalemia in patients with chronic kidney disease (CKD). However, evidence to
      prove the long-term tolerability and efficacy of SPS for the treatment of this
      condition is still missing. METHODS: In this retrospective, observational study,
      we enrolled 26 outpatients with stages 3-4 CKD who received oral therapy with low
      dose SPS for mild chronic hyperkalemia in the Outpatient Nephrology clinic of our
      Department during 2010-2016. We obtained medical records on side effects
      potentially attributable to SPS use, and we analyzed the changes in serum
      electrolytes before and after the initiation of SPS therapy. RESULTS: Serum
      potassium levels fell from 5.9 +/- 0.4 to 4.8 +/- 0.5 mmol/l (P < 0.001) over a
      median follow-up of 15.4 months (range 3-27 months). SPS use was associated with
      a slight, but significant elevation in serum sodium levels (139.5 +/- 2.9 vs
      141.2 +/- 2.4, P = 0.006), whereas serum calcium and phosphate remained unchanged
      before and after the initiation of SPS. We recorded ten episodes of recurrent
      serum potassium elevation >= 5.5 mmol/l, none of which required hospitalization
      or acute dialysis. No episode of colonic necrosis or any other serious drug
      related adverse event was observed. SPS therapy was well-tolerated, since only 1
      out of 26 patients discontinued SPS at 3 months due to gastrointestinal
      intolerance. CONCLUSION: This study suggests that low-dose SPS is well-tolerated
      and can effectively normalize elevated serum potassium over several weeks in CKD
      outpatients with mild chronic hyperkalemia.

PMID- 29027621
TI  - Use of carboxyhemoglobin as a biomarker of environmental CO exposure: critical
      evaluation of the literature.
AB  - Carbon monoxide (CO) poisoning is the primary cause for access to emergency
      department (ED) services for more than 50,000 persons in Europe and the USA every
      year. CO poisoning diagnosis is based on multiple factors and is usually
      confirmed by high carboxyhemoglobin (COHb) levels in the blood. We conducted a
      systematic evaluation of literature to investigate the usefulness of COHb as a
      biomarker of environmental CO exposure. We conducted an electronic search in
      Medline, Embase, and the Cochrane Library databases. We selected studies
      reporting high or low environmental CO concentrations, as well as COHb levels in
      exposed subjects presenting in ED or staying at home. We included 19 studies, but
      only 7 studies reported environmental CO concentration and proved a correlation
      between COHb and CO exposure in healthy and non-smoker subjects only. However,
      confounding factors were often incompletely assessed. The main symptoms reported
      were headache, nausea, vertigo and vomiting. COHb data stored in healthcare
      databases were used in six studies and provided useful information about
      symptoms, CO sources and patient characteristics. Most studies were classified at
      risk of bias. This review indicates that COHb is the most commonly used biomarker
      to assess CO exposure and seems to be useful. Further studies are needed to
      establish the reliability of COHb as a biomarker and/or explore other possible
      biomarkers. Surveillance systems of the general population, correlated with
      geographical locations and other confounding factors, could be important for CO
      exposure monitoring and the development of focused prevention programs.

PMID- 29027624
TI  - Cerebrovascular Complications and Polycythaemia Vera.

PMID- 29027622
TI  - Minimally invasive techniques for lumbar decompressions and fusions.
AB  - PURPOSE OF REVIEW: The purpose of this study is to summarize the recent
      literature investigating the use of minimally invasive (MIS) techniques in the
      treatment of lumbar degenerative stenosis, spondylolisthesis, and scoliosis.
      RECENT FINDINGS: MIS lumbar decompression and fusion techniques for degenerative
      pathology are associated with reduced operative morbidity, shortened length of
      hospital stay, and reduced postoperative pain and narcotics utilization. Recent
      studies with long-term clinical follow-up have demonstrated equivalence in
      clinical outcomes between open and MIS surgical procedures. Radiographically, MIS
      procedures provide adequate postoperative correction of coronal alignment.
      Correction of sagittal alignment, however, is more variable based on current
      reports. MIS techniques are both safe and effective in the treatment of lumbar
      degenerative pathologies. While some studies have reported on long-term outcomes
      and costs associated with MIS procedures, more investigation into these topics is
      still necessary. Additionally, further work is required to analyze the training
      requirements and learning curves of MIS procedures to better promote adoption
      amongst surgeons.

PMID- 29027623
TI  - Prospective observational study on the first 51 cases of peripheral blood stem
      cell transplantation from unrelated donors in Japan.
AB  - The Japan Marrow Donor Program (JMDP) has facilitated unrelated peripheral blood
      stem cell transplantation (URPBSCT) since 2010. We conducted a prospective
      multicenter observational study to evaluate the feasibility of such
      transplantation. Between 2011 and 2014, 51 patients underwent URPBSCT from 8/8
      allele-matched donors for hematological malignancies. The median age of the
      patients was 50 years; 21 had high-risk disease. Myeloablative conditioning
      regimens were used in 31 patients, and tacrolimus based graft-versus-host disease
      (GVHD) prophylaxis was used for all patients. The cumulative rate of engraftment
      was 96%. With a median follow-up period of 610 days for survivors, 100-day and 1
      year overall survival rates were 86 and 59%, respectively. The cumulative
      incidence of non-relapse mortality and relapse at 1 year were 14 and 35%,
      respectively. The incidence of grade II to IV acute GVHD at 100 days and
      extensive type of chronic GVHD at 1 year were 25 and 32%, respectively. The
      probability of overall survival was comparable with that of bone marrow
      transplantation from HLA matched-unrelated donors in Japan, although the
      incidence of chronic GVHD was higher. Further follow-up with more patients is
      clearly warranted to establish the optimal use of URPBSCT together with the
      approaches of minimizing chronic GVHD.

PMID- 29027625
TI  - Serum C3 complement levels in ANCA associated vasculitis at diagnosis is a
      predictor of patient and renal outcome.
AB  - AIM: To determinate the prognostic significance of low serum C3 at the time of
      diagnosis of ANCA-associated vasculitis (AAV). METHODS: Our cohort included 75
      consecutive patients with AAV diagnosed from January 2005 to December 2015. C3
      levels were measured at the time of diagnosis. Patients were divided into two
      groups, those with low serum C3 levels (< 0.9 g/l) and those with normal serum C3
      levels (0.9-1.8 g/l). We analysed association between serum C3 levels and both
      combined and singularly patient and renal survival (ESRD). Small number of
      relapsed patients did not allow for the statistical analysis to be performed as
      to weather the low serum C3 is associated with relapse rate in AAV patients.
      RESULTS: Low serum C3 levels were significantly associated with worse combined
      end-point patient and renal survival (HR 3.079; 95% CI 1.231-7.701; p = 0.016),
      and on multivariate adjusted analysis association remained significant (HR 2.831;
      95% CI 1.093-7.338; p = 0.032). For both end-points individually low serum C3
      levels were significantly associated with poorer patient survival (HR 6.378; 95%
      CI 2.252-18.065; p < 0.001; on multivariate adjusted analysis HR 4.315 95% CI
      1.350-13.799; p = 0.014) and renal survival (HR 3.207; 95% CI 1.040-9.830; p =
      0.043; on multivariate adjusted analysis HR 3.679; 95% CI 1.144-11.827; p =
      0.029). In our study there was no significant association between serological and
      patohistological phenotypes and serum C3 levels. CONCLUSION: Lower serum C3
      levels at the diagnosis is associated with poorer patient and renal outcomes in
      AAV patients.

PMID- 29027627
TI  - Association of TNF-alpha-3959T/C Gene Polymorphisms in the Chinese Population
      with Intracranial Aneurysms.
AB  - Recent studies have demonstrated that cytokines play an important role in the
      pathogenesis of intracranial aneurysm (IA). Tumor necrosis factor-alpha (TNF
      alpha) is an important proinflammatory cytokine, which was shown to influence the
      development of IA, but there is no research data from China. Hence, the purpose
      of this study was to explore the relationship between TNF-alpha polymorphisms and
      IA in China. The association of genetic variants of TNF-alpha gene expression was
      investigated in a Chinese population with IA. The TNF-alpha-3959T>C(rs1799964),
      4127C>A(rs1800630), 4133C>T(rs1799724), 4184C>T(rs4248158), and 4752G>A(rs361525)
      gene polymorphisms in 192 IA cases and 112 controls were analyzed using
      polymerase chain reaction (PCR). Differences in genotype and allele frequencies
      between patients and controls were tested. There were no significant differences
      in 4127C>A (p = 0.072), 4133C>T (p = 0.373), 4184C>T (p = 0.749), and 4752G>A (p
      = 0.184) genotype frequencies between the IA group and the control group. But
      this case-control association study revealed that TNF-alpha-3959T>C (p < 0.001)
      was significantly associated with increased risk of IA. These results suggested
      that a novel TNF-alpha locus was found to be closely correlated with the
      occurrence of IA in Chinese.

PMID- 29027629
TI  - Combined analysis of the preoperative and postoperative prognostic nutritional
      index offers a precise predictor of the prognosis of patients with gastric
      cancer.
AB  - PURPOSE: The prognostic nutritional index (PNI) is considered useful for
      predicting the prognosis of patients with gastric cancer (GC). This retrospective
      study investigated the relationship between both the pre- and postoperative PNI
      and the prognosis of GC patients. METHODS: The subjects of this study were 254
      patients who underwent curative surgery for histopathologically diagnosed GC.
      RESULTS: Patients were divided according to their pre- and postoperative PNI as
      follows: preoperative PNI of >= 52 (pre-PNIHigh), preoperative PNI of < 52 (pre
      PNILow), postoperative PNI of >= 49 (post-PNIHigh), and postoperative PNI of < 49
      (pre-PNILow). Both pre- and postoperative PNI were significantly associated with
      GC prognosis. Patients were then divided as follows: group A, patients with pre
      PNIHigh and post-PNIHigh; group B, patients with either pre-PNIHigh and post
      PNILow or pre-PNILow and post-PNIHigh; and group C, patients with pre-PNILow and
      post-PNILow. The 5-year survival rates were 100.0, 83.0, and 67.1% for groups A,
      B, and C, respectively. Multivariate analysis indicated that the combination of
      pre- and postoperative PNI was an independent prognostic indicator. CONCLUSIONS:
      Combined analysis of the pre- and postoperative PNI offers accurate information
      about the prognosis of patients with GC.

PMID- 29027630
TI  - Plasma cell myeloma mimicking classical Hodgkin lymphoma in the bone marrow.

PMID- 29027631
TI  - Detrimental roles of TNF-alpha in the antiphospholipid syndrome and de novo
      synthesis of antiphospholipid antibodies induced by biopharmaceuticals against
      TNF-alpha.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disease that is characterized by
      arterial and/or venous thrombosis and/or recurrent pregnancy losses. Obstetric
      APS (OAPS) is considered as a distinct entity from vascular APS (VAPS). In the
      absence of any additional disease, APS is designated as primary (PAPS), while the
      term secondary APS (SAPS) is used when other diseases are associated.
      Catastrophic APS (CAPS) is characterized by the rapid development of multiple
      thrombosis in various vital organs. The presence of antiphospholipid antibodies
      (aPL Abs) is considered as a laboratory criterion for APS diagnosis. aPL Abs
      cause an increase in systemic and decidual TNF-alpha levels in experimental model
      of APS (eAPS), while paradoxically, administration of TNF-alpha blockers has been
      associated with de novo synthesis of aPL Abs in patients with various autoimmune
      diseases. While eAPS provides evidence for the fact that application of TNF-alpha
      blockers has beneficial effects, lack of randomized prospective studies is the
      main obstacle for consideration of TNF-alpha blockers administration as a
      therapeutic option not for all, but at least for selected cases of APS patients
      despite compelling evidence for detrimental roles of TNF-alpha for both VASP and
      OAPS. This article represents a review of previously published reports on
      detrimental roles of TNF-alpha in APS, reports on the application of anti-TNF
      alpha agents in eAPS and articles that reported de novo synthesis of aPL Abs
      induced by biopharmaceuticals against TNF-alpha.

PMID- 29027626
TI  - Emerging roles for LPP in metastatic cancer progression.
AB  - LIM domain containing proteins are important regulators of diverse cellular
      processes, and play pivotal roles in regulating the actin cytoskeleton. Lipoma
      Preferred Partner (LPP) is a member of the zyxin family of LIM proteins that has
      long been characterized as a promoter of mesenchymal/fibroblast cell migration.
      More recently, LPP has emerged as a critical inducer of tumor cell migration,
      invasion and metastasis. LPP is thought to contribute to these malignant
      phenotypes by virtue of its ability to shuttle into the nucleus, localize to
      adhesions and, most recently, to promote invadopodia formation. In this review,
      we will examine the mechanisms through which LPP regulates the functions of
      adhesions and invadopodia, and discuss potential roles of LPP in mediating
      cellular responses to mechanical cues within these mechanosensory structures.

PMID- 29027628
TI  - The Prognostic Significance of Measurable ("Minimal") Residual Disease in Acute
      Myeloid Leukemia.
AB  - PURPOSE OF REVIEW: The purpose of this review was to evaluate recent literature
      on detection methodologies for, and prognostic significance of, measurable
      ("minimal") residual disease (MRD) in acute myeloid leukemia (AML). RECENT
      FINDINGS: There is no "one-fits-all" approach to MRD testing in AML. Most
      exploited to date are methods relying on immunophenotypic aberrancies (identified
      via multiparameter flow cytometry) or genetic abnormalities (identified via PCR
      based assays). Current methods have important shortcomings, including the lack of
      assay platform standardization/harmonization across laboratories. In parallel to
      refinements of existing technologies and data analysis/interpretation, new
      methodologies (e.g., next-generation sequencing-based assays) are emerging that
      eventually may complement or replace existing ones. This dynamic evolution of MRD
      testing has complicated comparisons between individual studies. Nonetheless, an
      ever-growing body of data demonstrates that a positive MRD test at various time
      points throughout chemotherapy and hematopoietic cell transplantation identifies
      patients at particularly high risks of disease recurrence and short survival even
      after adjustment for other risk factors.

PMID- 29027632
TI  - Let us talk about eggs! Professional resistance to elective egg vitrification and
      gendered medical paternalism.
AB  - In this paper, by applying a feminist bioethical perspective, we identify a new
      form of medical paternalism that still shapes contemporary legal policies on
      human egg cryopreservation performed without medical reasons. The fear of
      negligent, careless women who opt to delay their pregnancy for mere convenience
      is a widely known gender biased stereotype. Nevertheless, the opinions and
      judgments of medical professionals on this issue have not yet been sufficiently
      explored by in-depth research. In this essay, therefore, first we look at the
      broader bioethical, legal, and social aspects of human egg cryopreservation. In
      the second part of the paper we discuss a unique qualitative study conducted with
      professionals working at Hungarian IVF clinics. We argue, based on a bioethical
      analysis of the collected data, that when new reproduction technologies provide
      opportunities for women to widen their range of reproductive choices, the
      traditional forms of medical paternalism can be reinforced by gendered
      paternalism, as well. We identify several elements of gendered paternalism that
      characterized the attitudes of the IVF staff and discuss the professionals'
      resistance to elective egg freezing and vitrification of eggs for the future. We
      conclude by suggesting directions for future policy. Although we focus on the
      Hungarian case in this paper, we are aware that similar attitudes can be observed
      in some other countries where this technology has become available and requested
      by women, but where they also face difficulties in their access to it.

PMID- 29027633
TI  - Multi-Modality Imaging in the Evaluation and Treatment of Mitral Regurgitation.
AB  - OPINION STATEMENT: Mitral regurgitation (MR) is frequent and associated with
      increased mortality and morbidity when severe. It may be caused by intrinsic
      valvular disease (primary MR) or ventricular deformation (secondary MR). Imaging
      has a critical role to document the severity, mechanism, and impact of MR on
      heart function as selected patients with MR may benefit from surgery whereas
      other will not. In patients planned for a surgical intervention, imaging is also
      important to select candidates for mitral valve (MV) repair over replacement and
      to predict surgical success. Although standard transthoracic echocardiography is
      the first-line modality to evaluate MR, newer imaging modalities like three
      dimensional (3D) transesophageal echocardiography, stress echocardiography,
      cardiac magnetic resonance (CMR), and computed tomography (CT) are emerging and
      complementary tools for MR assessment. While some of these modalities can provide
      insight into MR severity, others will help to determine its mechanism.
      Understanding the advantages and limitations of each imaging modality is
      important to appreciate their respective role for MR assessment and help to
      resolve eventual discrepancies between different diagnostic methods. With the
      increasing use of transcatheter mitral procedures (repair or replacement) for
      high-surgical-risk patients, multimodality imaging has now become even more
      important to determine eligibility, preinterventional planning, and
      periprocedural guidance.

PMID- 29027634
TI  - A Randomized Controlled Trial to Assess the Impact of Proper Insulin Injection
      Technique Training on Glycemic Control.
AB  - INTRODUCTION: Improper injection technique can negatively affect glycemic control
      and treatment tolerability. We assessed the impact of structured insulin
      injection training on glycemic control. METHODS: We compared changes in glycated
      hemoglobin (A1C) and fasting plasma glucose following structured insulin
      injection training in a 6-month pilot study in patients with type 1 or 2
      diabetes. Patients were recruited from mobile clinics in Moscow, Russia, and
      randomized into three groups. Groups 1 and 2 received structured injection
      training, and group 3 did not. Group 1 received 4-mm needles sufficient for each
      injection; groups 2 and 3 provided their own needle supply. Changes in insulin
      total daily dose (TDD), injection technique, needle reuse, and lipohypertrophy
      (LH) were assessed. RESULTS: Of 120 patients enrolled, 116 were included in all
      analyses (group 1, n = 43; group 2, n = 35; group 3, n = 38). At 6 months, mean
      [95% CI] reductions in A1C were significant in groups 1 and 2 (- 1.00% [10.9
      mmol/mol (- 1.3 to - 0.6)] and - 1.00% [10.9 mmol/mol (- 1.4 to - 0.7)],
      respectively; P < 0.001 for both), but not in group 3 (- 0.02% [0.2 mmol/mol (-
      1.2 to 1.6)]). Increases in insulin TDD, however, were similar and significant
      across groups (approximately 6 IU; P < 0.05). Injection technique improved, and
      needle reuse and LH declined in groups 1 and 2, but not in group 3. CONCLUSIONS:
      Little is known about the glycemic impact of insulin injection training. We found
      that structured training and the use of short pen needles can improve injection
      technique, leading to significant A1C reductions and decreased rates of LH.

PMID- 29027636
TI  - Polymorphisms in interleukins 17A and 17F genes and periodontitis: results from a
      meta-analysis.
AB  - Polymorphisms in inflammatory genes such as interleukins 17A and 17F are
      associated with the risk of development of periodontitis, although the results
      remain contradictory. Hence, the aim of this study was perform a meta-analysis
      focusing on two polymorphisms (rs2275913 and rs763780) in interleukins 17A and
      17F genes, respectively, in both chronic (CP) and aggressive periodontitis (AgP).
      A review in literature was performed in several databases for studies published
      before 25, September 2016. The meta-analysis was obtained through the review
      manager statistical software (version 5.2) with odds ratio (OR) calculation and
      funnel plot (P < 0.05) for heterogeneity, as well as the comprehensive meta
      analysis software (version 3.3.070) for the assessment of publication bias. Seven
      articles with 1540 participants composed the results in which the mutant allele
      in the rs2275913 polymorphism did not present significant association with the
      risk of CP or AgP (OR 1.56, 95% CI 0.77, 3.15, P = 0.21; OR 1.12, 95% CI 0.05,
      23.44, P = 0.94, respectively) nor was the mutant allele in rs763780 associated
      with the risk of CP (OR 1.19, 95% CI 0.80, 1.76, P = 0.39) or AgP (OR 1.07, 95%
      CI 0.63, 1.84, P = 0.79). No bias of publication was observed by Egger's and
      Begg's tests in any allelic evaluation. This meta-analysis showed a non
      significant association between the polymorphisms rs2275913 and rs763780 in
      interleukins 17A and 17F genes and chronic and aggressive periodontitis in the
      allelic evaluation.

PMID- 29027637
TI  - Vaccine adjuvants: smart components to boost the immune system.
AB  - Vaccination is an effective approach to prevent the consequences of infectious
      diseases. Vaccines strengthen immunity and make individuals resistant to
      infections with pathogens. Although conventional vaccines are highly immunogenic,
      they are associated with some safety issues. Subunit vaccines are safe, but they
      require adjuvants to stimulate the immune system because of their weaker
      immunogenicity. Adjuvants are entities incorporated into vaccines to increase the
      immunogenic responses of antigens. They play a crucial role in increasing the
      potency and efficacy of vaccines. Different adjuvants have different modes of
      action; therefore, a better understanding of their immunology could provide
      guidance for the development of novel adjuvants. Numerous studies have been
      conducted using different types of adjuvants to characterize their potency and
      safety; however, in practice, only few are used in human or animal vaccines. This
      review aims to introduce the different modes of action of adjuvants and give
      insight into the types of adjuvants that possess the greatest potential for
      adjuvanticity.

PMID- 29027639
TI  - Robotic laparoendoscopic single-site benign gynecologic surgery: a single-center
      experience.
AB  - The da Vinci Xi surgical system was released with several upgrades and
      modifications compared to the previous robotic generations to facilitate minimal
      invasive surgery. Herein, we present our preliminary experience of robotic
      laparoendoscopic single-site gynecologic surgery performed for benign indications
      with the da Vinci Xi robotic system in a single center. Thirty-five female
      patients underwent robotic single-site surgery between June 2016 and January
      2017. The median console time for hysterectomy with or without salpingo
      oophorectomy was 41 min. The median intracorporeal vaginal cuff closure time was
      18 min. Two cases (5.7%) were converted to robotic-assisted multiport surgery.
      There was one major intraoperative complication (2.9%). None of the patient
      required blood transfusion. When comparing our first 12 cases to subsequent 12
      cases of R-LESS hysterectomy, there was a statistically significant decrease in
      surgical times and estimated blood loss. On logistic regression analysis, no
      association was detected between BMI and port entry time (OR 0.93, 95% CI 0.83
      1.04, p = 0.23), console time (OR 0.98, 95% CI 0.94-1.02, p = 0.37), cuff closure
      time (OR 0.9, 95% CI 0.76-1.09, p = 0.33), operative time (OR 1, 95% CI 0.98
      1.01, p = 0.97), and estimated blood loss (OR 0.98, 95% CI 0.96-1.01, p = 0.33).
      Our preliminary experience with robotic laparoendoscopic single-site surgery
      using the da Vinci Xi system has demonstrated feasibility and safety in select
      patients. Further studies with greater number of patients in multiple settings
      will help us to fully elucidate the role of da Vinci Xi surgical system in single
      site gynecologic surgery.

PMID- 29027640
TI  - The utility of botulinum toxin A in the repair of distal biceps tendon ruptures.
AB  - PURPOSE: The purpose of our study is to report the outcomes and complications in
      patients who underwent distal biceps tendon repair with the use of Botulinum
      toxin A (BoNT-A) as an adjunct to surgery. METHODS: A retrospective review of 14
      patients who underwent 15 distal biceps tendon repairs was performed. All
      repaired tendons had their correlating muscle bellies injected intraoperatively
      with a mixture of 100U of BoNT-A and 10 ml of normal saline. Each patient was
      evaluated for surgical and post-operative complications and followed with
      Disabilities of the Arm, Shoulder and Hand (DASH) Disability Scores. RESULTS: The
      cohort was exclusively male, 14/14 (100%). The mean age at procedure was 52.1
      years (range: 29-65 years). Types of injuries repaired included: 12 acute biceps
      tendon ruptures, one chronic partial (> 50% of tendon) biceps tear, and two
      chronic biceps ruptures. Average final follow-up was 32.9 months (SD: 19.6;
      range: 7.07-61.72). Average time to repair of chronic injury was 5.75 months
      (range: 2-12 months). There were no intraoperative complications, and all
      patients were discharged home on the day of surgery. Average DASH score at latest
      follow-up was 4.9 (range: 0.0-12.5). All patients had return of function of
      paralyzed muscle prior to final follow-up. One patient required an incision and
      drainage for a deep infection 1 week post-operatively, without any further
      complications. Another patient required operative removal of heterotopic
      ossification located around the tendon fixation site, which was the result of a
      superficial infection treated with antibiotics 2 weeks post-operatively. This
      patient later healed with improvement in supination/pronation range-of-motion and
      no further complications. CONCLUSIONS: Injection of BoNT-A is safe and effective
      to protect distal biceps tendon repair during the early phases of bone-tendon
      healing. CLINICAL RELEVANCE: BoNT-A may is safe and effective to protect distal
      biceps tendon repair. The utility of BoNT-A as an adjunct to surgical repair may
      be applicable to acute or chronic tears as well as repairs in the non-compliant
      patient without decreases in functional scores after return of function of the
      biceps muscle. LEVEL OF EVIDENCE: Level 4.

PMID- 29027638
TI  - Fluconazole versus mould-active triazoles for primary antifungal prophylaxis in
      adult patients with acute lymphoblastic leukemia: clinical outcome and cost
      effectiveness analysis.
AB  - This study evaluated the clinical and cost-effectiveness of prophylactic use of
      fluconazole versus mould-active triazoles (voriconazole and posaconazole) in
      adult patients with acute lymphoblastic leukemia (ALL). A decision analytical
      model was developed with inputs from a 7-year retrospective study (2009-2016) of
      103 consecutive adult patients with ALL who received antifungal prophylaxis.
      Information on the administration of antifungal agents, clinical outcomes, and
      costs were collected. One-way sensitivity analyses and probabilistic sensitivity
      analysis were performed. The mould-active triazoles group was associated with
      higher life-years (3.71 vs 3.59) and lower total costs (US$4886 vs US$5722) per
      patient compared with fluconazole. One-way sensitivity analyses revealed that
      varying all of the key variables in the model did not affect the robustness of
      the results. Probabilistic sensitivity analysis demonstrated that mould-active
      triazoles had a probability of 77.1 and 90.1% of providing a dominant and cost
      effective option relative to fluconazole, respectively. Mould-active triazoles
      should be regarded as preferable to fluconazole as the first-line prophylactic
      for adult patients with ALL accompanied by uncommon severe vinca alkaloid-induced
      neurotoxicity. However, the results reported here should be interpreted with
      caution owing to the observational nature of the data.

PMID- 29027641
TI  - Cost Effectiveness of Imatinib, Dasatinib, and Nilotinib as First-Line Treatment
      for Chronic-Phase Chronic Myeloid Leukemia in China.
AB  - BACKGROUND AND OBJECTIVE: Tyrosine kinase inhibitors (TKIs) have obvious effects
      on chronic myeloid leukemia (CML), but they are expensive in China. Moreover, the
      overall cost of treatment of CML is high and the medical economic burden of
      patients with CML on the government is heavy. This study tested the cost
      effectiveness of imatinib, nilotinib, and dasatinib as first-line treatment in
      Chinese patients who were first diagnosed with chronic myeloid leukemia in the
      chronic phase (CML-CP). METHODS: A state-transition Markov model combining
      clinical effectiveness, utility, and cost data was used. Sensitivity analyses
      were conducted to determine the robustness of the model outcomes. RESULTS: The
      imatinib-first, dasatinib-first, and nilotinib-first strategy offered patients
      9.76, 9.87, and 9.72 quality-adjusted life years (QALYs) at a cost of
      US$303,502.42, US$381,681.03, and US$305,509.92 over 20 years, respectively. The
      nilotinib-first strategy exhibited the lowest utility and highest price and was
      thus eliminated. An incremental cost-effectiveness analysis of the imatinib-first
      strategy and the dasatinib-first strategy showed that the dasatinib-first
      strategy yielded an incremental cost-utility ratio (ICER) of 710,714.64 $/QALY
      compared with the imatinib-first strategy, which exceeded the threshold; hence,
      the dasatinib-first strategy was not cost effective and was eliminated. The
      results were robust for multiple sensitivity analyses. CONCLUSION: From the
      perspective of the Chinese medical system, imatinib is likely to be more cost
      effective than dasatinib and nilotinib for patients who were first diagnosed with
      CML-CP.

PMID- 29027643
TI  - Contribution of Theory of Mind, Executive Functioning, and Pragmatics to
      Socialization Behaviors of Children with High-Functioning Autism.
AB  - Social difficulties are a key aspect of autism, but the intervening factors are
      still poorly understood. This study had two objectives: to compare the profile of
      ToM skills, executive functioning (EF), and pragmatic competence (PC) of children
      with high-functioning autism (HFA) and children with typical development (TD),
      and analyze their mediator role in social functioning. The participants were 52
      children with HFA and 37 children with TD matched on age, intelligence quotient,
      and expressive vocabulary. Significant differences were found on measures of ToM,
      both explicit and applied, EF, and PC between children with HFA and TD. Multiple
      mediation analysis revealed that applied ToM skills and PC mediated the relations
      between autism symptoms and social functioning. Implications for social cognitive
      interventions to address these findings are discussed.

PMID- 29027642
TI  - Familial MPN Predisposition.
AB  - Chronic myeloproliferative neoplasms (MPN) characteristically arise from a
      somatic mutation in the pluripotent hematopoietic stem cell, and most common
      recurring mutations are in the JAK2, CALR, and cMPL genes. However, these
      mutations are not founder mutations, but mainly drive the disease phenotype and a
      pre-existing germline predisposition has been long speculated, but has not been
      clearly defined to date. Genome-wide association studies in family clusters of
      MPN have identified a number of genetic variants that are associated with
      increased germline risk for developing clonal MPN. The strongest association
      discovered so far is the presence of JAK2 46/1 haplotype, and subsequently, many
      studies have found additional variants in other genes, most notably in TERT gene.
      However, these still account for a small fraction of familial MPN, and more in
      depth studies including whole genome sequencing are needed to gain better insight
      into familial genetic predisposition of clonal MPNs.

PMID- 29027645
TI  - Preventive effect of pre-warming, hot compress, and pH adjustment in oxaliplatin
      induced venous pain.
AB  - Background Venous pain induced by peripheral intravenous administration of
      oxaliplatin remains clinically unresolved. Objective The aim of this study was to
      determine the efficacy of comprehensive intervention care for venous pain in
      colorectal cancer patients receiving oxaliplatin. Setting A Japanese tertiary
      hospital. Method We treated all outpatients after April 2012 with comprehensive
      intervention care including pre-warming of the oxaliplatin solution, use of a hot
      compress, and pH adjustment by combination with dexamethasone. We retrospectively
      reviewed the electronic medical records from colorectal cancer patients who had
      received oxaliplatin via a peripheral vein between December 2009 and June 2014.
      Main outcome measures The primary endpoint of this study was the incidence of
      venous pain at the administration site during oxaliplatin infusion, according to
      injection site reaction grade >= 2. Results We evaluated 271 treatment courses in
      59 patients. Venous pain occurred in 42 courses (15.5%) among 26 patients.
      Multivariate logistic regression analysis revealed that female gender and body
      mass index >= 25 kg/m2 were significantly associated with an increased risk of
      venous pain during all courses (adjusted odds ratio [OR]: 3.18, 95% confidence
      interval [CI] 1.35-7.92; P < 0.01; and adjusted OR: 3.37, 95% CI 1.26-9.40; P =
      0.02, respectively), whereas comprehensive intervention care were significantly
      associated with reduced risk of venous pain during all courses (adjusted OR:
      0.10, 95% CI 0.02-0.44; P < 0.01). Conclusion Comprehensive intervention care is
      a clinical treatment option for oxaliplatin-induced peripheral venous pain in
      patients with colorectal cancer, especially females with obesity.

PMID- 29027644
TI  - Treatment of empty sella associated with visual impairment: a systematic review
      of chiasmapexy techniques.
AB  - PURPOSE: Chiasmapexy is a poorly described surgical procedure adopted to correct
      the downward displacement of suprasellar visual system (SVS) into an empty sella
      (ES) causing visual worsening. The aim of our study is to define the indications
      for extradural and intradural chiasmapexy. METHODS: A systematic literature
      review has been performed on MEDLINE database (US National Library of Medicine),
      including only articles that depicted cases of surgically treated patients
      affected by ES and progressive delayed visual worsening. Moreover, we have
      reported three cases of secondary ES syndrome (SESS) with visual worsening
      treated in our Department with transsphenoidal (TS) microsurgical intradural
      approach. Finally, we have compared the results of extradural and intradural
      chiasmapexy described in literature. RESULTS: The etiology of visual impairment
      is different in primary and secondary ESS. In primary ESS (PESS) the only
      predisposing factor is a dehiscence of diaphragma sellae, and the anatomical
      distortion caused by displacement of optic chiasm or traction of pituitary stalk
      and infundibulum may determine a direct injury of neural fibers and ischemic
      damage of SVS. In PESS the mechanical elevation of SVS performed through
      extradural approach is sufficient to resolve the main pathologic mechanism. In
      SESS, arachnoidal adhesions play an important role in addition to downward
      herniation of SVS. Consequently, the surgical technique should provide elevation
      of SVS combined to intradural release of scar tissue and arachnoidal adhesions.
      In treatment of SESS, the intradural approaches result to be more effective,
      guaranteeing the best visual outcomes with the lowest complications rates.
      CONCLUSIONS: The intradural chiasmapexy is indicated in treatment of SESS,
      instead the extradural approaches are suggested for surgical management of PESS.

PMID- 29027646
TI  - Prevalence of obstructive sleep apnea among obese toddlers and preschool
      children.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a common disorder estimated at 1-5%
      in the school-aged children. With the obesity prevalence reaching staggering
      rates globally, OSA in obese adolescents is estimated to be 4-5-folds higher than
      their lean peers. There is a paucity of data regarding obesity-related OSA in
      children 6 years and less. This is particularly relevant as OSA is associated
      with neurocognitive deficits. The aim of this study is to evaluate the prevalence
      of OSA among obese toddlers and preschool children and further to determine what
      other factors may be associated with the presence of OSA. METHODS: A
      retrospective study involving children <=6 years, identified from two Canadian
      pediatric tertiary care centers who had an in-lab polysomnography (PSG). Obesity
      was defined by a BMI of > 95th percentile for age and gender or a z-score of > 2.
      OSA was diagnosed if the obstructive apnea-hypopnea index (OAHI) was greater than
      2 events per hour. RESULTS: There were 60 participants included; the mean age was
      4.4 years (standard deviation [SD] +/- 1.7), mean BMI z-score was 3.0 (SD +/-
      1.2). Of these, 22/60 (36.6%) had OSA. Compared with the non-OSA group, the OSA
      group had a higher Epworth sleepiness score (p = 0.03) and were more likely to
      snore (p = 0.01). CONCLUSION: Young obese children should be assessed for OSA. A
      history of snoring and daytime sleepiness may be useful indicators to facilitate
      triage for a PSG, especially in resource-limited settings.

PMID- 29027647
TI  - Dasatinib-associated reversible demyelinating peripheral polyneuropathy in a case
      of chronic myeloid leukemia.
AB  - Tyrosine kinase inhibitors (TKIs) are essential for the treatment of chronic
      myeloid leukemia (CML). Adverse effects of dasatinib have been reported; however,
      few reports have highlighted the association between dasatinib and demyelinating
      peripheral neuropathy (DPN). We report a patient with CML who developed acute
      onset of DPN associated with dasatinib therapy. A 46-year-old Japanese woman was
      treated with dasatinib for 7 months after the diagnosis of CML and she achieved a
      major molecular response (MMR). However, dysphagia, hoarseness, and muscle
      weakness progressively developed over 2 weeks. Nerve conduction studies revealed
      extensive demyelinating changes. Dasatinib was discontinued and the patient
      received intravenous immunoglobulin (IVIg), resulting in resolution of the
      symptoms. However, 1 month after the re-initiation of dasatinib therapy, muscle
      weakness developed again, indicating possible involvement of dasatinib in the
      development of DPN. She was then treated with IVIg, followed by prednisolone and
      nilotinib instead of dasatinib. These treatments eventually led to improvements
      of the symptoms and helped her achieve an MMR. This case suggests that dasatinib
      may carry risks of DPN possibly through immune-mediated disorders. It is
      clinically important to realize that dasatinib can cause extensive DPN, and a
      quick discontinuation and a switch to another TKI may be indicated.

PMID- 29027648
TI  - Prevention of Type 2 Diabetes with the Chinese Herbal Medicine Tianqi Capsule: A
      Systematic Review and Meta-Analysis.
AB  - INTRODUCTION: Prevention of the rapid growth in incidence of type 2 diabetes
      (T2DM) is a big challenge for clinicians. In China, many trials have indicated
      that Tianqi capsule, which contains several Chinese herbal medicines as part of a
      large healing system called traditional Chinese medicine, could decrease the
      incidence of T2DM. The review assessed the effectiveness of Tianqi capsule in
      prevention of T2DM. METHODS: Seven electronic databases were searched to identify
      eligible trials published from the inception of the databases up until May 1,
      2017. Randomized controlled trials (RCTs) of Tianqi capsule for impaired glucose
      tolerance (IGT) were included. Data extraction and quality assessment were
      performed according to the Cochrane review standards. A random or a fixed effect
      model was used to analyze outcomes which were expressed as risk ratios (RRs) or
      mean differences (MD), and I 2 statistics were used to assess heterogeneity.
      RESULTS: Six trials were identified that included 1027 subjects. Meta-analysis
      showed that subjects who received Tianqi capsule plus lifestyle modification (LM)
      were less likely to progress to T2DM compared to controls (RR 0.55, 95% CI 0.44
      0.68). Subjects who received Tianqi capsule plus LM were more likely to have
      glucose return to normal compared to controls (RR 0.69; 95% CI 0.62-0.78); and
      they had reduced fasting plasma glucose (FBG) (MD - 0.35; 95% CI - 0.55 to -
      0.16) and 2-h plasma glucose (2 h PG) (MD - 1.04; 95% CI - 1.75 to - 0.32). There
      was no statistical difference between the two groups for IGT stabilized incidence
      (RR 0.89; 95% CI 0.71-1.12). No obvious adverse events occurred. CONCLUSION: In
      patients with IGT, Tianqi capsule reduced the risk of progression to T2DM and
      increased the possibility of regression toward normoglycemia. As a result of the
      limited number of RCTs and the methodological drawbacks of the included studies,
      the results should be interpreted with caution.

PMID- 29027650
TI  - Correction to: Role of intestinal microbiome in American ginseng-mediated colon
      cancer prevention in high fat diet-fed AOM/DSS mice.
AB  - This article was originally published with the wrong title.

PMID- 29027651
TI  - Syndesmis aethopharynx Westervelt & Kozloff, 1990 (Rhabdocoela: Umagillidae): a
      revisitation supported by scanning electron microscopy and molecular analyses.
AB  - Species of Syndesmis Francois, 1886 are rhabdocoel platyhelminths typically found
      in echinoids. Our knowledge of this group is based on old and insufficient
      studies, generally representing light microscopy-based species descriptions.
      Syndesmis aethopharynx Westervelt & Kozloff, 1990 is an understudied endosymbiont
      of Paracentrotus lividus (Lamarck), which is likely to have been confused with
      the type-species, i.e. Syndesmis echinorum Francois, 1886, in the literature. In
      this work, S. aethopharynx is revisited based on new data on surface morphology
      and phylogeny and basic ecological data are provided. Scanning electron
      microscopy analysis revealed that the whole ventral region of the worm is
      equipped with cilia, which supports the assumption that the unciliated epidermal
      area reported for some species of umagillids, likewise endosymbiotic in
      echinoderms, is an apomorphy. Following the results of the molecular phylogenetic
      analysis, species of Syndesmis are closely-related to symbionts of other
      echinoderms, i.e. holothurians, and like them, may have evolved from some free
      living or symbiotic Provorticidae ancestor. Syndesmis spp. may stand for a key
      group in studying the evolution of feeding strategies in rhabdocoels, as their
      phylogenetic position is between intestinal and coelomic symbionts, and since
      both the digestive tube and perivisceral fluid were recorded as sites of
      infection. The infection levels were low, likely reflecting the aggregated
      distribution of the host and the fragile nature of the symbiont.

PMID- 29027649
TI  - Sex-Specific Effects of Combined Exposure to Chemical and Non-chemical Stressors
      on Neuroendocrine Development: a Review of Recent Findings and Putative
      Mechanisms.
AB  - PURPOSE OF REVIEW: Environmental toxicants and psychosocial stressors share many
      biological substrates and influence overlapping physiological pathways.
      Increasing evidence indicates stress-induced changes to the maternal milieu may
      prime rapidly developing physiological systems for disruption by concurrent or
      subsequent exposure to environmental chemicals. In this review, we highlight
      putative mechanisms underlying sex-specific susceptibility of the developing
      neuroendocrine system to the joint effects of stress or stress correlates and
      environmental toxicants (bisphenol A, alcohol, phthalates, lead, chlorpyrifos,
      and traffic-related air pollution). RECENT FINDINGS: We provide evidence
      indicating that concurrent or tandem exposure to chemical and non-chemical
      stressors during windows of rapid development is associated with sex-specific
      synergistic, potentiated and reversed effects on several neuroendocrine endpoints
      related to hypothalamic-pituitary-adrenal axis function, sex steroid levels,
      neurotransmitter circuits, and innate immune function. We additionally identify
      gaps, such as the role that the endocrine-active placenta plays, in our
      understanding of these complex interactions. Finally, we discuss future research
      needs, including the investigation of non-hormonal biomarkers of stress. We
      demonstrate multiple physiologic systems are impacted by joint exposure to
      chemical and non-chemical stressors differentially among males and females.
      Collectively, the results highlight the importance of evaluating sex-specific
      endpoints when investigating the neuroendocrine system and underscore the need to
      examine exposure to chemical toxicants within the context of the social
      environment.

PMID- 29027652
TI  - Correction to: Tumor Volume Doubling Time as a Dynamic Prognostic Marker for
      Patients with Hepatocellular Carcinoma.
AB  - The original version of this article unfortunately contained an error in
      corresponding author e-mail. It was submitted and published as
      kimkim70@amc.seoul.kr instead of kimkm70@amc.seoul.kr.

PMID- 29027653
TI  - Comparison of dexmedetomidine and fentanyl to prevent haemodynamic response to
      skull pin application in neurosurgery: double blind randomized controlled trial.
AB  - BACKGROUND: Skull pin application during craniotomy is a highly noxious stimulus.
      Therefore, the attenuated effect between dexmedetomidine and fentanyl was
      investigated. METHOD: A randomized, double-blind controlled trial included sixty
      patients, randomly allocated into groups A and B. After patients entered the
      operative room, blood pressure and heart rate were measured (T1). At 5 minutes
      after propofol induction (T2), group A received dexmedetomidine 1 ug kg-1 whereas
      group B received normal saline. At 3 minutes before skull pin insertion (T3),
      group B received a single bolus of fentanyl 1 ug kg-1 whereas group A received
      normal saline. The hemodynamic responses were recorded at 1 minute before skull
      pin insertion (T4), during skull pin insertion (T5), then repeated every minute
      for 5 minutes (T6-T10). RESULTS: Controlling blood pressure in the
      dexmedetomidine group (Group A) was better than in the fentanyl group (Group B)
      at T4 and T10 (P < 0.05) and T5-T8 (P < 0.01) for systolic blood pressure whereas
      diastolic blood pressure was significantly different at T4 and T8 (P < 0.05) and
      T5-T7 (P < 0.01). Mean arterial pressure, also was better controlled in group A
      at T4 and T10 (P < 0.05) and T5-T8 (P < 0.01). The heart rate in group A was
      lower than group B at T9 (P < 0.05) and T3-T6 (P < 0.01). Regarding adverse
      events, 11 hypertensive and 2 hypotensive responses occurred in group B whereas
      group A just only had 7 incidences of hypotension. CONCLUSION: The attenuated
      effect of dexmedetomidine infusion is significantly greater than fentanyl
      infusion.

PMID- 29027654
TI  - Pharmacokinetic drug-drug interactions in the intensive care unit - single-centre
      experience and literature review.
AB  - BACKGROUND: Drug-drug interactions constitute a serious health hazard in everyday
      clinical practice in critically ill patients. Drug-drug interactions may be
      pharmacokinetic or pharmacodynamic in their nature. We aimed to investigate the
      quantity and quality of possible drug-drug interactions, and their possible side
      effects in intensive care unit patients in a 12-month period. METHODS: This
      retrospective study covered data on pharmacological treatment of 43 consecutive
      patients (11 females, 32 males) aged 62 +/- 15 years, hospitalized between
      January 2015 and February 2016. Pharmacokinetic DDIs were identified and graded.
      Only severe and clinically important drug-drug interactions were subjected for
      further analysis. RESULTS: Median baseline SAPS III was 53 (IQR 38-67) points.
      Median intensive care unit stay was 12 (6-25) days. Subjects were treated with a
      median number of 22 (12-27) drugs. We identified 27 (16-41) possible drug-drug
      interactions per patient, including 3 (1-7) drug-drug interactions of a severe
      grade. The total number of severe and clinically important drug-drug interactions
      was 253 of which 227 were analyzed in detail. No possible side-effects of drug
      drug interactions were identified. CONCLUSIONS: DDIs as well as their side
      effects are challenging regarding their precise evaluation, especially due to the
      need for multidrug treatment in critically ill patients. Concentration-controlled
      therapy should be recommended, especially for treatment with vancomycin, digoxin
      and valproate. Pantoprazole should be a proton pump-inhibitor of choice. Drug
      dose modification is necessary in combined treatment with fluconazole and
      amiodarone or rifampicin. From a clinical point of view, the most important
      impact of drug-drug interactions is on antibiotic treatment effectiveness,
      especially with meropenem when valproate is also prescribed.

PMID- 29027655
TI  - Determinants of immediate failure of noninvasive mechanical ventilation outside
      the intensive care unit.
AB  - BACKGROUND: This study aimed to characterize which are the early determinants of
      immediate failure of the use of noninvasive mechanical ventilation (NIMV) outside
      the ICU. METHODS: This prospective study included patients who were admitted to
      the Military Hospital in Guayaquil, Ecuador. Each variable was analyzed
      independently by using a multiple logistic regression model toward establishing
      an association with the event. RESULTS: A total of 249 cases of NIMV over a 10
      year period of its application outside the ICU was included in the study. Fifty
      five (22.10%) patients were transferred to the ICU, A multivariate analysis
      showed that the determinants of immediate NIMV failure outside the ICU were the
      following: age (OR: 1.12; P = 0.03); SBP (OR: 1.04; P = 0.001); HR (OR: 1.66; P <
      0.0001); pCO2 (OR: 1.16; P = 0.007); pO2 (OR: 1.35; P = 0.003); levels of IPAP
      (OR: 1.35; P < 0.0001); and the number of quadrants affected, as shown in a chest
      X-ray (OR: 1.40; P < 0.0001). CONCLUSIONS: The number of affected quadrants in a
      chest X-ray, tachyarrhythmia and hypoxemia may be useful in the initial decision
      in the use of NIMV outside the ICU. High values of IPAP, the persistence of
      elevated pCO2, arterial hypotension, and age could be useful as a second
      screening associated with immediate NIMV failure outside the ICU.

PMID- 29027657
TI  - Practical issues of nutrition during continuous renal replacement therapy.
AB  - Continuous renal replacement therapy (CRRT) in critically ill patients has
      significant impact on one's ability to provide efficient nutritional therapy.
      CRRT may help in the prevention of intestinal oedema and the maintenance of the
      proper function of the gastrointestinal tract by enabling strict control of the
      fluid balance. It facilitates early introduction of nutrition via the enteral
      route, as well as allowing for the composition of high-volume feeding mixtures.
      It is necessary to take into consideration that during CRRT, together with blood
      purification of toxic substances, nutritive elements are also eliminated to some
      extent (micro- and macronutrients). In this article, the authors discuss the
      impact of CRRT on nutritive elements loss, energetic balance and present the
      principles of adjusting feeding prescriptions to changes implied by CRRT.

PMID- 29027656
TI  - Pulmonary complications after non-cardiac surgeries: temporal patterns and risk
      factors.
AB  - BACKGROUND: Postoperative complications are the primary determinants of survival
      following major surgery. We aimed to characterize the early perioperative risk
      factors for postoperative pulmonary complications (POPCs) in patients undergoing
      major non-cardiac surgeries. METHODS: This study utilized a multicenter
      prospective observational cohort design. Adult patients undergoing non-cardiac
      surgeries and admitted to 21 Brazilian ICUs were screened for inclusion in the
      study. POPCs were defined as the presence of acute pulmonary oedema, nosocomial
      pneumonia, and extubation failure in the postoperative period. RESULTS: Of the
      581 patients enrolled, 110 (19%) had at least one POPC, of whom 5% had acute
      pulmonary oedema, 10% extubation failure while 10% had pneumonia. Most cases of
      pulmonary oedema occurred in the first week after surgery, while pneumonia was
      more frequently a later occurrence. The mortality rate was significantly higher
      in the group with POPCs compared to the group of patients without POPCs (62% vs.
      11%, RR: 5.1, 95% CI: 4.23-7.69; P < 0.001). A low functional capacity (RR: 4.6,
      95% CI: 2.1-10.0), major surgery (RR: 3.6, 95% CI: 1.2-10.7), preoperative
      hemodynamic instability (RR: 3.4, 95% CI: 1.1-10.6), alcoholism (RR: 3.3, 95% CI:
      1.0-10.7), unplanned surgery (RR: 2.3, 95% CI: 1.0-5.2), the SOFA score (RR: 1.1,
      95% CI: 1.0-1.2), and increased central venous pressure (RR: 1.1, 95% CI: 1.0
      1.1) were independent predictors of POPCs. CONCLUSIONS: Pulmonary complications
      are common in intensive care units after major non-cardiac surgeries. Awareness
      of the risk factors for POPCs may help multidisciplinary teams develop strategies
      to prevent these complications.

PMID- 29027658
TI  - Pathological drainage of the right superior vena cava into the left atrium
      diagnosed in a 37-year-old patient in postpartum period: a case report.

PMID- 29027659
TI  - A novel cotton WRKY gene, GhWRKY6-like, improves salt tolerance by activating the
      ABA signaling pathway and scavenging of reactive oxygen species.
AB  - WRKY transcription factors are transcriptional regulators of signaling pathways
      involved in biotic and abiotic stress responses. In this study, we report that
      ectopic expression of the GhWRKY6-like gene significantly improved salt tolerance
      in Arabidopsis thaliana while silencing the GhWRKY6-like increase the sensitivity
      to abiotic stresses in cotton. GhWRKY6-like was localized to the nucleus.
      Expression of GhWRKY6-like was remarkably induced by salt, polyethylene glycol
      (PEG) and abscisic acid (ABA) treatments. For further characterization, the
      GhWRKY6-like gene was cloned and transformed into Arabidopsis. Our findings
      showed that the germination rate and root length were significantly improved in
      plants overexpressing GhWRKY6-like vs wild type (WT) under salt, mannitol and ABA
      treatments. Additionally, the overexpressing lines showed greater salt tolerance
      than WT plants in soil. In addition, overexpressing plants accumulated less H2 O2
      and malondialdehyde (MDA), while higher proline content, superoxide dismutase
      (SOD) and peroxidase (POD) activities were detected under salt and osmotic
      stresses. In contrast, virus-induced gene silencing (VIGS) of GhWRKY6-like in
      cotton showed enhanced sensitivity compared to WT plants during salt and drought
      stresses. Additionally, expression analysis of stress-responsive genes in GhWRKY6
      like Arabidopsis revealed that there was increased expression of genes involved
      in the ABA signaling pathway (AtABF4, AtABI5 and AtMYC2) and osmotic stress
      (AtSOS2, AtRD29a and AtRD29b). Our results revealed that GhWRKY6-like enhanced
      salt tolerance in Arabidopsis by scavenging reactive oxygen species and
      regulating the ABA signaling pathway. We suggest that overexpression of the
      GhWRKY6-like gene in cotton will enhance tolerance against salt, drought and
      osmotic stresses.

PMID- 29027661
TI  - Negotiating Ethical Paradoxes in Conducting a Randomized Controlled Trial:
      Aligning Intervention Science with Participatory Values.
AB  - In this article, we describe ethical tensions we have faced in the context of our
      work as intervention scientists, where we aim to promote social justice and
      change systems that impact girls involved in the juvenile legal system. These
      ethical tensions are, at their core, about resisting collusion with systems of
      control while simultaneously collaborating with them. Over the course of
      designing and implementing a randomized controlled trial (RCT) of an ecological
      advocacy intervention for girls, called ROSES, ethical paradoxes crystalized and
      prompted us to engage in critical reflection and action toward the aim of moving
      away from conducting research on legal-system-involved girls and moving toward a
      more democratic, participatory process of inquiry with girls. Our experience
      revealed two intertwined paradoxes that ultimately served generative purposes.
      First, in collaborating with legal system stakeholders, we observed a single
      story of girls' pathology narrated for girls, without girls, and ultimately
      internalized by girls. Second, in reflecting critically on the ethical
      implications of our study design, it became clear that the design was grounded in
      a medical model of inquiry although the intervention we sought to evaluate was
      based, in part, on resistance to the medical model. We describe emergent ethical
      tensions and the solutions we sought, which center on creating counternarratives
      and counterspaces that leverage, extend, and disrupt our existing RCT. We detail
      these solutions, focusing on how we restructured our research team to enhance
      structural competence, shifted the subject of inquiry to include the systems in
      which youth are embedded, and created new opportunities for former research
      participants to become co-researchers through formal roles on an advisory board.

PMID- 29027662
TI  - Prediction and scale in savanna ecosystems.
AB  - Contents Summary 52 I. Introduction 52 II. Determinants of savanna vegetation
      structure 53 III. Are trees in savannas really more heterogeneous? 53 IV. Are
      trees in savannas a 'slow' variable? 54 V. Are trees in savannas spatially
      patterned? 55 VI. Conclusions 55 Acknowledgements 55 References 56 SUMMARY:
      Savannas are highly variable systems, and predicting variation, especially in the
      tree layer, represents a major unresolved challenge for forecasting biosphere
      responses to global change. Prediction to date has focused on disentangling
      interactions between resource limitation and chronic disturbances to identify
      what determines local savanna vegetation heterogeneity. By focusing at too fine a
      scale, this approach overlooks: sample size limitation arising from sparse tree
      distributions; stochasticity in demographic and environmental processes that is
      preserved as heterogeneity among tree populations with slow dynamics; and spatial
      self-organization. Renewed focus on large (1-50 ha) permanent plots and on
      spatial patterns of tree-layer variability at even larger landscape spatial
      scales (>=1000s of ha) promises to resolve these limitations, consistent with the
      goal of predicting large-scale biosphere responses to global change.

PMID- 29027660
TI  - Maternal emotion dysregulation, parenting stress, and child physiological anxiety
      during dark-enhanced startle.
AB  - Maternal emotion dysregulation (ED) plays a crucial role in the development of
      psychopathology in children. The current study aimed to investigate parenting
      stress as a mediator of the relationship between maternal emotion dysregulation
      and child startle potentiation, with child sex as a moderator. Mothers were
      interviewed to obtain self-report of maternal ED and parenting stress and child's
      dark-enhanced startle (DES) response was measured using electromyographic
      recordings of the eye-blink muscle during the delivery of acoustic probes. We
      found that maternal ED was positively correlated with both her parenting stress
      and her child's DES. A bootstrap analysis yielded a full mediation of the
      association between ED and child DES via parenting stress. Child sex was not a
      significant moderator of these relationships. These results suggest that maternal
      ED has important consequences for the intergenerational transmission of risk and
      also highlight the interaction of behavioral and biological mechanisms of risk.

PMID- 29027663
TI  - The role of cardiac vagal tone and inhibitory control in pre-schoolers' listening
      comprehension.
AB  - This study investigated the role of basal cardiac activity and inhibitory control
      at the beginning of the school year in predicting oral comprehension at the end
      of the year in pre-schoolers. Forty-three, 4-year-olds participated in the study.
      At the beginning of the school year children's electrocardiogram at rest was
      registered followed by the assessment of inhibitory control as well as verbal
      working memory and verbal ability. At the end of the year all children were
      administered a listening comprehension ability measure. A stepwise regression
      showed a significant effect of basal cardiac vagal tone in predicting listening
      comprehension together with inhibitory control and verbal ability. These results
      are among the first to show the predictive role of basal cardiac vagal tone and
      inhibitory control in pre-schoolers' oral text comprehension, and offer new
      insight into the association between autonomic regulation of the heart,
      inhibitory control, and cognitive activity at a young age.

PMID- 29027664
TI  - Navigating Community Development Conflicts: Contested Visions of Poverty &
      Poverty Alleviation.
AB  - This article explores an ethical dilemma that arose from the author's involvement
      in a project intended to identify and address the needs of seven batey
      communities in the Dominican Republic. In the summer of 2014, the author
      conducted a large-scale needs assessment to inform strategic planning for a
      foundation that was invested in community development work in those communities.
      Through a collaborative process, the author worked with the foundation,
      representatives of the migrant communities, and other researchers to develop
      survey and focus group tools that were administered to 1,360 and 54 people,
      respectively. Data collection, analysis, and dissemination proceeded as planned.
      The conflict and resulting ethical dilemma emerged at the point of data
      interpretation and strategic planning, processes that revealed that the different
      parties held conflicting theories of poverty. The ideological conflicts related
      to why poverty exists, who is responsible for it, and what should be done about
      it made proceeding with the project ethically tenuous for the author. The author
      describes the values and theories of ethics on which she relied to navigate this
      challenge, as well as reflections on her continued participation in the community
      development process.

PMID- 29027665
TI  - Impact of Digital Technologies on Novel Endpoint Capture in Clinical Trials.
AB  - Digital technologies have been successfully deployed in clinical settings for
      many years, yet recent advances in hardware and analytic capabilities have driven
      an explosion in interest over the potential of digital medicine to change how
      drugs are developed, centering on how we interact with patients, treat patients,
      and capture information about patients.

PMID- 29027666
TI  - Alexander George Karczmar (1917-2017).
AB  - The neurochemistry community at large and the Advisory Board of The International
      Symposia on Cholinergic Mechanisms mourn the loss of Alexander George Karczmar,
      the elected Honorary President of these international symposia, who passed away
      peacefully in his Chicago home at the age of 100 on August 17, 2017. For many of
      us Alex was the essence of cholinergic signaling, and personified its versatile
      power to send messages between the brain and the peripheral tissues and organs,
      and to connect between body and soul.

PMID- 29027667
TI  - Co-inhibitory profile and cytotoxicity of CD57+ PD-1- T cells in end-stage renal
      disease patients.
AB  - Blockade of the CD80/86-CD28 pathway by belatacept after kidney transplantation
      is associated with an increased risk of rejection compared with standard,
      calcineurin inhibitor (CNI)-based therapy. CD28- T cells, which express CD57, are
      not susceptible to belatacept treatment. High numbers of CD4+ CD57+ programmed
      death 1 (PD-1)- T cells pretransplantation have been associated with a higher
      chance of rejection, although conflicting data have been reported. To investigate
      the working mechanism behind this possible higher chance of rejection, we studied
      the expression of co-inhibitory molecules (CD223, CD244 and PD-1), proliferative
      capacity and cytotoxic potential of fluorescence activated cell sorted (FACS)
      CD4+ CD57+ PD-1- and CD8+ CD57+ PD-1- T cells, and their CD57- control
      populations, after alloantigen stimulation. The effect of belatacept on the
      cytotoxic capacity of pretransplantation peripheral blood mononuclear cells from
      20 patients who received belatacept post-transplantation was also tested.
      Expression of co-inhibitory molecule CD223 increased by approximately 10-fold
      after allogeneic stimulation in all four T cell subsets. Proliferation and up
      regulation of CD244 and PD-1 was observed for CD4+ CD57- PD-1- T cells after
      allogeneic stimulation, but no up-regulation of these markers occurred on CD8+ T
      cells or CD4+ CD57+ PD-1- T cells. However, CD4+ CD57+ PD-1- T cells and, to a
      lesser extent, CD8+ CD57+ PD-1- T cells displayed higher cytotoxicity as
      indicated by granzyme B expression. Belatacept inhibited the cytotoxic potential
      of CD4+ CD57+ PD-1- T cells (median of inhibition 31%, P < 0.01) and CD8+ CD57+
      PD-1- T cells (median of inhibition 10%, P < 0.05). In conclusion, alloantigen
      activated CD4+ CD57+ PD-1- T cells exhibited a less proliferative but more
      cytotoxic profile than their CD57- counterparts. Their cytotoxic capacity can be
      inhibited partly by belatacept and was not associated with development of
      rejection after kidney transplantation.

PMID- 29027668
TI  - Decreased sorbitol synthesis leads to abnormal stamen development and reduced
      pollen tube growth via an MYB transcription factor, MdMYB39L, in apple (Malus
      domestica).
AB  - Sugars produced by photosynthesis not only fuel plant growth and development, but
      may also act as signals to regulate plant growth and development. This work
      focuses on the role of sorbitol, a sugar alcohol, in flower development and
      pollen tube growth of apple (Malus domestica). Transgenic 'Greensleeves' apple
      trees with decreased sorbitol synthesis had abnormal stamen development, a
      decreased pollen germination rate and reduced pollen tube growth, which were all
      closely related to lower sorbitol concentrations in stamens. RNA sequencing and
      quantitative RT-PCR analyses identified reduced transcript levels during stamen
      development and pollen tube growth in the transgenic trees of a stamen-specific
      MYB39-like transcription factor, MdMYB39L, and of its putative target genes
      involved in hexose uptake, cell wall formation and microsporogenesis. Suppressing
      MdMYB39L expression in pollen via antisense oligonucleotide transfection
      significantly reduced the expression of its putative target genes and pollen tube
      growth. Exogenous sorbitol application during flower development partially
      restored MdMYB39L expression, stamen development, and pollen germination and tube
      growth of the transgenic trees. Addition of sorbitol to the germination medium
      also partially restored pollen germination and tube growth of the transgenic
      trees. We conclude that sorbitol plays an essential role in stamen development
      and pollen tube growth via MdMYB39L in apple.

PMID- 29027669
TI  - Changes in Public Attitudes and Perceptions about Homelessness Between 1990 and
      2016.
AB  - Public attitudes on homelessness can and has influenced policies and services for
      homeless populations. This study surveyed national public attitudes about
      homelessness in the 21st century and examined changes in attitudes in the past
      two decades. An online survey of public attitudes about homelessness was
      conducted with 541 U.S. adults across 47 states in November 2016 using Amazon
      Mechanical Turk. Survey results were compared to two public surveys conducted in
      1990. Compared to previous surveys, the current sample endorsed more compassion,
      government support, and liberal attitudes about homelessness. The largest changes
      were related to increased support for homeless individuals to use public spaces
      for sleeping and panhandling. When asked about the demographic composition of the
      homeless population, the contemporary sample tended to overestimate the
      proportions who were young and racial/ethnic minorities, while underestimating
      the proportions who were married, or had mental health or substance abuse
      problems. Together, the findings suggest there has been an increase in compassion
      and liberal attitudes toward homelessness in the past two decades. Greater
      support for homeless individuals during an era of economic recessions and
      governmental homeless initiatives presents opportunities for new public health
      approaches to address homelessness.

PMID- 29027670
TI  - Chiari-like malformation in two cats.
AB  - Two male, neutered, domestic, shorthaired cats were evaluated for progressive
      paresis and ataxia. Neurological examinations suggested a spinal cord lesion in
      each case. Complete blood examination and cerebrospinal fluid analysis were
      unremarkable in both cats. MRI revealed malformation of the occipital bone with
      herniation of the cerebellar vermis through the foramen magnum but without
      syringomyelia. Chiari-like malformation was suspected in both patients. MRI
      repeated one year later in both cats because of progression of clinical signs
      yielded the same findings as the initial scans. Foramen magnum decompression in
      one cat was associated with resolution of clinical signs.

PMID- 29027671
TI  - Ethical Challenges of Personal Disclosure in Gaining Entry with Religious
      Congregations.
AB  - This is a story about learning how to navigate my social identities as a non
      religious gay man attempting to conduct data-based consultation with a religious
      congregation. Beyond my own growth in knowing myself better, this story speaks to
      the larger ethical challenge of how we build trust in community relationships,
      and in particular how much of our personal selves we need to disclose in the
      process of an individual or group deciding to work with us. Individuals and
      groups make decisions to work with us based on who they perceive us to be; thus,
      what is our ethical obligation to disclose aspects of who we are to promote full
      informed consent? To illustrate this ethical challenge of personal disclosure, I
      tell the story of discussions I had with three different religious leaders and a
      congregational committee about potentially working together. Throughout these
      stories, I reflect on my own messy process of growth as a window into the more
      general question of how we navigate our identities and values as community
      psychologists in the work we do with communities.

PMID- 29027672
TI  - Inside-Out: Representational Ethics and Diverse Communities.
AB  - The purpose of this paper is to write about insights and special considerations
      for researchers who are, to some degree, "insiders" to the communities they study
      by expanding on the concept of representational ethics as applied to research in
      community psychology with diverse and marginalized groups. Representational
      ethics refers to the ways that researchers, artists, or corporations represent
      the identities of the people they portray in their communications. As community
      psychologists we generate and disseminate knowledge about the communities we work
      with, and in that process, create narratives about the people who participate in
      our studies. In preparing a report on psychological issues among Evangelical
      Christian refugees from the former Soviet Union, Dina Birman struggled with her
      portrayal of this group and her own status of being both an insider and an
      outsider to this community. When investigating academic aspirations and
      psychological distress among Muslim high school students, Ashmeet Oberoi was
      forced to acknowledge the one-sidedness of the discourse on autonomy and cultural
      socialization of Muslim adolescents. In her research with Cuban-educated doctors
      in Miami, Florida, Wendy Moore encountered similar issues as she considered how
      to represent gender dynamics among her participants.

PMID- 29027673
TI  - Community Power Structure Analysis and the Ethical Considerations of "Studying
      Up".
AB  - This narrative outlines our challenges in studying power and power structures
      within an individual-level ethical framework. Taking a social ethics perspective,
      we share the story of our "sticky situation" (Campbell, ) that transpired during
      a multi-year community partnership. We were asked, by our community partners, to
      help collect interview data without informed consent. As a team of community
      engaged university researchers, we were faced with a seemingly easy ethical
      situation (no consent, no research) that had unexpectedly complicated and long
      lasting consequences. This experience revealed to us how community-engaged
      research and action, under a traditional ethics framework, can often work to
      protect those in positions of power and offer little to disrupt the status quo.
      Reflecting on the tension between individual and social ethics, we discuss the
      limitations of an individual-level framework, including the definitions for
      respect for persons, justice, and beneficence, on our ability as a field to
      understand, critique, and contribute to the dismantling of oppressive power
      structures.

PMID- 29027674
TI  - Reflexivity in Counterspaces Fieldwork.
AB  - Reflexivity is an important tool for navigating ethically important moments in
      fieldwork. It may be particularly useful in situations where the researcher has
      the potential to undermine the conduct of the study and/or the well-being
      enhancing role of counterspaces. In this article, I explore my use of reflexivity
      to traverse ethically important moments I encountered while investigating a
      counterspace for African-American youth who had been incarcerated. The ethical
      challenge concerned whether and how to continue this study in light of realizing
      that I held implicit biases toward the research participants. I describe my
      process for arriving at a decision and propose key considerations for the use of
      reflexivity in supporting ethical fieldwork within counterspaces.

PMID- 29027675
TI  - Ultrasound-Guided Percutaneous Dilatational Tracheostomies in 2 Difficult
      Airways.
AB  - Ultrasound has become a rapid, safe, and easy-to-use tool for anesthesiologists.
      It reduces complications, morbidity, and mortality, especially in patients with
      anatomic abnormalities in whom a traditional approach may be both difficult and
      risky. We report 2 cases of symptomatic patients with a difficult airway due to
      displacement of the trachea by a neck mass. Real-time ultrasound imaging was
      performed for percutaneous dilatational tracheostomies, identifying important
      structures, without any complications.

PMID- 29027676
TI  - Toxicokinetics of strychnine and brucine after the oral administration of Biqi
      capsule to rats by RRLC-MS/MS.
AB  - Biqi capsule is a well-known traditional Chinese medicine formula that has been
      widely applied for the clinical treatment of such diseases as rheumatoid
      arthritis, scapulohumeral periarthritis and cervical spondylopathy. However,
      there is concern regarding the toxicity of Biqi capsule owing to its active
      ingredients, strychnine and brucine. To investigate the toxicokinetics of
      strychnine and brucine after oral administration of Biqi capsule to rats, a
      sensitive and simple rapid-resolution liquid chromatography/tandem mass
      spectrometry method was developed to determine the levels of strychnine and
      brucine in rat plasma. Chromatographic separation was performed on a Capcell Pak
      C18 MG II (3.0 MUm, 2.0 * 35 mm) column by gradient elution with acetonitrile and
      0.2% formic acid as the mobile phase. The method was validated over the range of
      0.25-250 ng/mL for strychnine and 0.025-25 ng/mL for brucine. The intra- and
      inter-day accuracies of strychnine and brucine in rat plasma were 100.3-106.6 and
      90.75-106.1% respectively, and the precisions were within 14.2%. The established
      method was successfully applied to the toxicokinetic study of strychnine and
      brucine after single and multiple oral administration of Biqi capsule to male and
      female rats at 0.4, 0.8 and 1.6 g/kg doses. The results showed different
      toxicokinetic characteristics in the different groups.

PMID- 29027677
TI  - Comparison of plasma pharmacokinetics of Tanreqing solution between intratracheal
      aerosolization and intravenous injection in rats.
AB  - A rapid ultra high performance liquid chromatography tandem mass spectrometry
      method was developed for the simultaneous analysis of baicalin, oroxylin A-7-O
      beta-d-glucoronide and chlorogenic acid in rats plasma, and applied to comparison
      of pharmacokinetics of Tanreqing solution between intratracheal aerosolization
      and intravenous injection. Results of the analytical method validation assay
      showed high sensitivity, accuracy and suitable recovery. Results of
      pharmacokinetics showed similar decline phases for baicalin, oroxylin A-7-O-beta
      d-glucoronide and chlorogenic acid in two different delivery routes. The half
      lives of intratracheal aerosolization and intravenous injection were 0.90 and
      1.22 h for baicalin, 0.47 and 0.17 h for oroxylin A-7-O-beta-d-glucoronide and
      0.22 and 0.13 h for chlorogenic acid, and this implies that compounds were
      retained in the lung for a relatively short time. This study was the first to
      provide important pharmacokinetics information for traditional Chinese medicine
      delivery to the lung.

PMID- 29027678
TI  - Evaluation of Carotid Plaque Neovascularization in Patients With Coronary Heart
      Disease on Contrast-Enhanced Ultrasonography.
AB  - OBJECTIVES: To examine the repeatability of quantitative time-intensity curve
      analysis of neovascularization within carotid plaques with contrast-enhanced
      ultrasonography (US) and to investigate carotid plaque neovascularization in
      patients with coronary heart disease using contrast-enhanced US and the
      correlation between risk factors and acute coronary syndrome (ACS). METHODS:
      Sixty patients with ACS and 60 with stable coronary artery disease (CAD)
      underwent conventional carotid and contrast-enhanced US, and plaque enhancement
      was observed and analyzed quantitatively. Carotid contrast-enhanced US was
      performed within 1 month of ACS occurrence. Interobserver and intraobserver
      variability of the measurements was assessed. The peak signal intensity was the
      maximum number of contrast microbubbles that local tissues could accumulate,
      reflecting the local microvascular density and representing the capillary volume.
      RESULTS: The ACS group had higher low-density lipoprotein cholesterol (mean +/-
      SD, 3.21 +/- 0.75 versus 2.53 +/- 0.71 mmol/L; P < .01) and high-sensitivity C
      reactive protein (CRP; 3.76 +/- 0.19 versus 2. 93 +/- 0.15 mg/L; P < .01) levels
      than the stable CAD group. The proportion of soft plaques in the ACS group (81%)
      was higher than in the stable CAD group (53%). The proportion of plaque
      enhancement, peak signal intensity, and plaque-to-carotid lumen enhancement
      intensity ratio were higher in the ACS group than the stable CAD group. The peak
      signal intensity was correlated with the high-sensitivity CRP value. Logistic
      regression analyses indicated that age (65-74 years), high-sensitivity CRP, and
      enhancement intensity were correlated with the occurrence of ACS. The sensitivity
      and specificity of the peak signal intensity in carotid plaques were 80.0% and
      88.3%, respectively (cutoff value, 9.97 dB; area under the receiver operating
      characteristic curve, 0.865). The time-intensity curve measurements had good
      repeatability. CONCLUSIONS: Carotid plaque enhancement is a potential independent
      risk factor for ACS occurrence. These results illustrate the correlation of
      carotid plaque vulnerability with the coronary artery symptomatic state according
      to the common pathogenetic mechanism of atherosclerosis.

PMID- 29027679
TI  - High prevalence of betanodavirus barfin flounder nervous necrosis virus as well
      as red-spotted grouper nervous necrosis virus genotype in shellfish.
AB  - Using two serially executed PCRs, the discriminative multiplex two-step RT-PCR
      (DMT-2 RT-PCR) following the detection seminested two-step RT-PCR (DSN-2 RT-PCR),
      we found a high frequency presence of BFNNV genotype as well as RGNNV in various
      domestic and imported shellfish. This was definitely different from the previous
      reports of outbreaks and asymptomatic infection only by the RGNNV genotype in
      cultured finfish in Korea. Cultivation of NNV entrapped in shellfish was
      performed successfully by a blind passage. Thus, in an attempt to elucidate the
      epidemiology of betanodavirus, experiments conducted on 969 shellfish samples
      concluded that (i) distribution of NNV genotype, especially BFNNV, in shellfish
      is clearly different from that found in finfish of the world; (ii) unlike RGNNV,
      which showed a high rate in summer, BFNNV showed no seasonal variation and this
      result suggests BFNNVs in the marine environment remain fairly constant
      throughout the year; and (iii) the entrapped virus in shellfish was alive and
      culturable in vitro. These results are the first report of high level prevalence
      of in vitro culturable NNV in shellfish, for both BFNNV and RGNNV, which may
      present a potential risk in transmitting nodaviruses to host species in a marine
      environment.

PMID- 29027680
TI  - Determination of thiocyanate as a biomarker of tobacco smoke constituents in
      selected biological materials of human origin.
AB  - In order to protect human health, it is necessary to biomonitor toxic substances
      originating from tobacco smoke in biological materials sampled from persons with
      different exposures to tobacco smoke constituents. Thiocyanate anion is a
      biomarker of exposure to tobacco smoke components which is characterized by a
      relatively long half-life in the human body, i.e. 6 days. In this work, we
      present the results of thiocyanate determinations performed on samples of
      placenta, meconium, saliva, breast milk, sweat and blood. The placenta samples
      were subjected to accelerated solvent extraction with water. The thiocyanate
      concentrations were determined using ion chromatography. The analyzed biological
      materials were compared with regard to their applicability for biomonitoring
      toxic substances originating from tobacco smoke. The highest mean concentrations
      of thiocyanate were observed in the samples of biological materials collected
      from active smokers.

PMID- 29027681
TI  - The drivers of sea lice management policies and how best to integrate them into a
      risk management strategy: An ecosystem approach to sea lice management.
AB  - The control of sea lice infestations on cultivated Atlantic salmon is a major
      issue in many regions of the world. The numerous drivers which shape the
      priorities and objectives of the control strategies vary for different
      regions/jurisdictions. These range from the animal welfare and economic
      priorities of the producers, to the mitigation of any potential impacts on wild
      stocks. Veterinary ethics, environmental impacts of therapeutants, and impacts
      for organic certification of the produce are, amongst others, additional sets of
      factors which should be considered. Current best practice in both EU and
      international environmental law advocates a holistic ecosystem approach to
      assessment of impacts and risks. The issues of biosecurity and ethics, including
      the impacts on the stocks of species used as cleaner fish, are areas for
      inclusion in such a holistic ecosystem assessment. The Drivers, Pressures, State,
      Impacts, Responses (DPSIR) process is examined as a decision-making framework and
      potential applications to sea lice management are outlined. It is argued that
      this is required to underpin any integrated sea lice management (ISLM) strategy
      to balance pressures and outcomes and ensure a holistic approach to managing the
      issue of sea lice infestations on farmed stock on a medium to long-term basis.

PMID- 29027682
TI  - Comparative Study of Abdominal Muscle Thickness on Ultrasonography in Healthy
      Adolescents and Patients With Low Back Pain.
AB  - OBJECTIVES: Low back pain (LBP) is a common musculoskeletal disorder among
      different age groups, including adolescents. The purpose of this study was to
      compare the abdominal muscle thickness between healthy adolescents and those with
      LBP. METHODS: One hundred sixty healthy high school adolescents and 80 high
      school adolescents with LBP participated in the study. All participants were
      asked to complete a demographic questionnaire and also a visual analog scale and
      the Oswestry Disability Questionnaire to evaluate the pain intensity and
      functional disability. Then abdominal muscle thickness was examined with
      ultrasonography. RESULTS: The healthy high adolescents included 80 boys and 80
      girls, and the adolescents with LBP included 40 boys and 40 girls. The results
      showed a significant difference between healthy adolescents and those with LBP in
      terms of abdominal muscle thickness (P < .05). Patients with LBP had smaller
      abdominal muscles compared with healthy adolescents. No significant difference
      was found between the groups in terms of the subcutaneous fat dimension (P >
      .05). CONCLUSIONS: The thickness of abdominal muscles was lower in adolescents
      with LBP. Future studies with a larger sample and a wider age range are
      recommended to support the results of this study.

PMID- 29027683
TI  - Ultrasonographic Measurement of the Biceps Femoris Long-Head Muscle Architecture.
AB  - OBJECTIVES: Biceps femoris long-head architectural assessment using
      ultrasonography (US) has not been previously described in detail for both
      acquisition (image capture) and digitization (image measurement) processes, and
      the effect of the US window width is unknown. This study aimed to describe the
      reliability and test-retest minimum detectable difference of US-based biceps
      femoris architectural measurements. METHODS: Muscle length was determined by
      marking the muscle-tendon junction distances. Sonograms were acquired with a 6-cm
      image width and cropped for a 3-cm width in 3 assessments (n = 20 adults). Intra-
      and inter-rater reliability rates were determined for both image (3- and 6-cm
      widths) acquisition and digitizing processes separated and together (within
      session) for the biceps femoris fascicle length, fascicle angle, and muscle
      thickness measurements using intraclass correlation coefficients (ICCs) and
      Pearson (r) correlation coefficients. RESULTS: Muscle length was measured with
      high intra-rater (ICC = 0.93; r = 0.92) and inter-rater (ICC = 0.90; r = 0.90)
      reliability. Intra-rater (coefficient of variation, 0.2%-1.8%) and inter-rater
      (ICC = 0.79-0.99; r = 0.80-0.99) digitizing reliability rates were high. High
      intra-rater (ICC = 0.79-0.95; r = 0.79-0.95) and moderate-to-high inter-rater
      (ICC = 0.51-0.92; r = 0.70-0.93) session reliability rates were found for all
      architectural parameters for 6- and 3-cm images (intra-rater ICC = 0.77-0.93; r =
      0.79-0.93; inter-rater ICC = 0.63-0.98; r = 0.90-0.98). The inter-rater session
      reliability rates for both image acquisition and digitizing processes were higher
      for 6-cm images (ICC = 0.65-0.86; r = 0.67-0.87) than 3-cm images (ICC = 0.28
      0.93; r = 0.67-0.93). The minimum detectable differences for the 6-cm images were
      8.4 mm, 1.5  degrees , and 1.6 mm for fascicle length, fascicle angle, and muscle
      thickness, respectively. CONCLUSIONS: Ultrasonography can be used to reliably
      assess midmuscle architecture of the biceps femoris muscle when the same rater
      performs image acquisition and digitization.

PMID- 29027684
TI  - Chemical interaction between Lilium brownii and Rhizoma Anemarrhenae, the herbal
      constituents of Baihe Zhimu decoction, by liquid chromatography coupled to hybrid
      triple quadrupole linear ion trap mass spectrometer.
AB  - During the course of decoction, the components of herbal formula interact with
      each other, such that chemical extraction characteristics are altered. The crude
      drugs, Lilium brownii (Baihe) and Rhizoma Anemarrhenae (Zhimu), are the herbal
      constituents of Baihe Zhimu decoction, a traditional herbal formula. To
      investigate the chemical interaction between Baihe and Zhimu when decocting
      together, eight marker components in Baihe Zhimu decoction were simultaneously
      characterized and quantified in one run by a hybrid triple quadrupole linear ion
      trap mass spectrometer in the multiple reactions monitoring-information dependent
      acquisition-enhanced product ion mode. The results showed that Zhimu
      significantly suppressed the extraction of phenolic glycosides (the components
      from Baihe) when co-decocting, and Baihe clearly suppressed the extraction of
      xanthones and steroidal saponins (the components from Zhimu). Overall, the
      presently developed method would be a preferred candidate for the investigation
      of the chemical interaction between herbal medicines.

PMID- 29027685
TI  - RubisCO and the Search for Biomolecular Culprits of Planetary Change.

PMID- 29027686
TI  - Ultrasonography of the Sural Nerve: Normal and Pathologic Appearances.
AB  - Ultrasonography (US) of peripheral nerves has gained wide popularity because of
      the increased definition of modern high-frequency electronic transducers, as well
      as the well-known advantages of US, which include easy availability, low cost,
      and the possibility of realizing a dynamic examination. Traditionally, US has
      been deployed to assess the major nerves of the limbs. More recently, US has also
      been used to assess the normal appearance and pathologic changes of smaller
      subcutaneous nerves. The sural nerve is a small sensory nerve in the subcutaneous
      tissues of the calf that can be affected by a variety of disorders. This
      pictorial essay illustrates the normal anatomy of the sural nerve, the technique
      for its examination by US, as well as the US appearance of its main pathologic
      changes.

PMID- 29027687
TI  - Filter Adsorption of Anidulafungin to a Polysulfone-Based Hemofilter During CVVHD
      In Vitro.
AB  - Candidemia is frequent in critically ill patients, especially in combination with
      an acute kidney injury (AKI). Echinocandins generally are recommended for therapy
      of such infections. Recent studies found no need for dosage adjustment in
      patients with end-stage renal disease receiving hemodialysis, or patients with
      AKI receiving continuous venovenous hemofiltration. The aim of this in vitro
      study was to examine the adsorption of anidulafungin to the surface of the
      hemofilter during continuous venovenous hemodialysis (CVVHD) and its effect on
      anidulafungin concentrations. The concentration of anidulafungin in the dialyzed
      fluid, and the dialysate during CVVHD in vitro was examined using three different
      dialyzed fluids (saline; saline with 40 g/L human albumin; and a mixture of human
      erythrocytes and fresh frozen plasma). After the end of dialysis, the hemofilter
      was opened and portions of the filter capillaries were also analyzed to determine
      the amount of anidulafungin adsorbed. When dialyzing saline, about 99% of the
      anidulafungin used adsorbed to the hemofilter capillaries; in the experiments
      with saline with 40 g/L albumin, about 60% adsorbed to the hemofilter's surface,
      and when blood was dialyzed, 35% was found adsorbed after analyzing the filter
      capillaries. Anidulafungin was not detectable in the dialysate of any of the
      experiments, consequently the dialysis clearance was 0 mL/min. In conclusion,
      during CVVHD in vitro we found remarkable adsorption of anidulafungin to the
      hemofilter's surface, yet the effect on the tissue concentration needs further
      examination.

PMID- 29027688
TI  - Preoperative Ultrasonographic Assessment of the Anterior Pelvic Plane for
      Personalized Total Hip Replacement.
AB  - OBJECTIVES: Correct positioning of the acetabular component is a key factor in
      minimizing the risk of dislocation after total hip replacement (THR) surgery. A
      "safe" orientation of the cup is usually defined by 2 angles measured between its
      geometric axis and the anterior pelvic plane. However, in the current state-of
      the-art approach to THR surgery, the intraoperative orientation of the anterior
      pelvic plane cannot be measured. Even less is known about the functional
      orientation of the pelvis, which determines the postoperative orientation of the
      cup during the patient's everyday activities. The aim of this article is to
      present an original approach to personalized THR surgery, in which the necessary
      measurements are done preoperatively without interfering with the surgical work
      flow, and the individual orientation of the cup is obtained without navigation
      using standard tools that are available in the operating room. METHODS: To
      quantify the effect of the anatomic conditions on the final orientation of the
      cup, we measured the orientation of the anterior pelvic plane in 43 patients
      scheduled for THR using a newly developed noninvasive method based on
      ultrasonography and mobile devices. RESULTS: Our results confirm a large
      variability of the pelvic orientation in both supine and standing positions. We
      further show how this variability affects the final position of the cup and
      discuss its consequences for the patient. Finally, we explore a few practical
      solutions for individualized cup placement, including our own approach, which is
      based on tilting of the operating table. CONCLUSIONS: In this work, we show that
      the common guidelines used today for cup implantation can only be effectively
      applied to a small portion of the population. In most cases, it is crucial that
      the orientation of the cup is readjusted for the particular anatomy of the
      individual patient.

PMID- 29027689
TI  - Oral Mucosa Model for Electrochemotherapy Treatment of Dog Mouth Cancer: Ex Vivo,
      In Silico, and In Vivo Experiments.
AB  - Electrochemotherapy (EQT) is a local cancer treatment well established to
      cutaneous and subcutaneous tumors. Electric fields are applied to biological
      tissue in order to improve membrane permeability for cytotoxic drugs. This
      phenomenon is called electroporation or electropermeabilization. Studies have
      reported that tissue conductivity is electric field dependent. Electroporation
      numerical models of biological tissues are essential in treatment planning.
      Tumors of the mouth are very common in dogs. Inadequate EQT treatment of oral
      tumor may be caused by significant anatomic variations between dogs and tumor
      position. Numerical models of oral mucosa and tumor allow the treatment planning
      and optimization of electrodes for each patient. In this work, oral mucosa
      conductivity during electroporation was characterized by measuring applied
      voltage and current of ex vivo rats. This electroporation model was used with a
      spontaneous canine oral melanoma. The model outcomes of oral tumor EQT is applied
      in different parts of the oral cavity including near bones and the hard palate.
      The numerical modeling for treatment planning will help the development of new
      electrodes and increase the EQT effectiveness.

PMID- 29027690
TI  - Ultrasound-Guided Posterior Femoral Cutaneous Nerve Block: A Cadaveric Study.
AB  - OBJECTIVES: To identify any anatomic barriers to local anesthetic spread between
      the sciatic nerve (SN) and the posterior femoral cutaneous nerve (PFCN) at the
      level of the infragluteal crease and to describe a potential technique for an
      ultrasound (US)-guided subgluteal PFCN block in a cadaveric model. METHODS:
      Bilateral US-guided subgluteal injections of a colored latex solution were
      performed around the SN (15 mL) and PFCN (10 mL) in 4 unembalmed cadavers, for a
      total of 8 cadaver thighs. The specimens were dissected after latex
      polymerization to observe the spread of the latex solutions. RESULTS: With US
      guidance, the PFCN was visualized deep to the gluteus maximus and slightly
      superficial or lateral to the SN at the level of the infragluteal crease. The SN
      and PFCN were found on dissection to be coated with their respective colored
      latex in all 8 thighs. The SN and PFCN were consistently separated by the deep
      investing muscular fascia of the thigh, with only 2 thighs showing substantial
      mixing of latex injectates. CONCLUSIONS: The deep investing muscular fascia of
      the thigh appears to impede the spread of injectate between the SN and PFCN in a
      most unembalmed cadaver specimens. A US-guided subgluteal PFCN blockade may be a
      feasible technique to complement an SN block when complete anesthesia of the
      posterior thigh is required.

PMID- 29027691
TI  - Serum adenosine deaminase and xanthine oxidase activities in silver catfish
      naturally infected with Ichthyophthirius multifiliis: The influence of these
      enzymes on inflammatory and oxidative status.
AB  - Adenosine deaminase (ADA) activity, through adenosine (Ado) levels, as well as
      xanthine oxidase (XO) activity through uric acid levels exerts an essential role
      on immune and inflammatory responses during infectious diseases. Thus, the aim of
      this study was to evaluate the involvement of seric ADA and XO activities in the
      inflammatory and oxidative status of silver catfish naturally infected with
      Ichthyophthirius multifiliis. Seric ADA activity decreased, while Ado levels
      increased in infected animals compared to uninfected animals. Moreover, the seric
      XO activity increased in infected animals compared to uninfected animals,
      alongside the seric levels of uric acid, metabolites of nitric oxide (NOx) and
      reactive oxygen species (ROS). Based on this evidence, the downregulation of
      seric ADA activity exerts an anti-inflammatory profile, contributing to
      restricting the inflammatory process. The most important finding is that
      upregulation of seric XO activity leads to an excessive formation of uric acid,
      which contributes to oxidative and inflammatory processes. Moreover, uric acid
      induces the release of pro-inflammatory and pro-oxidative mediators, such NOx and
      ROS, which contribute directly to disease pathogenesis. In summary, the
      upregulation of XO activity may be considered a pathway involved in NOx and ROS
      production in silver catfish infected with I. multifiliis.

PMID- 29027692
TI  - Prenatal Diagnosis of a Urinoma and Dilated Azygous Vein.

PMID- 29027694
TI  - Can We Evaluate Hiatal Ballooning by Measuring the Anteroposterior Diameter With
      2-Dimensional Translabial Ultrasonography?
AB  - OBJECTIVES: To analyze the association between the anteroposterior hiatal
      diameter and pelvic organ prolapse and to determine whether 2-dimensional
      translabial ultrasonography can evaluate hiatal ballooning by measuring the
      anteroposterior diameter. METHODS: This study was a retrospective analysis of 312
      women seen for lower urinary tract symptoms or pelvic organ prolapse between
      December 2014 and July 2016. All women had an International Continence Society
      (ICS) Pelvic Organ Prolapse Quantification (POP-Q) system examination and 4
      dimensional translabial ultrasonography. The anteroposterior hiatal diameter was
      measured in the midsagittal plane, and the hiatal area was measured in the
      minimal axial plane during the maximal Valsalva maneuver. RESULTS: Valid data
      from 294 patients were analyzed. International Continence Society POP-Q stage 0
      was found in 121 women, stage 1 in 49, stage 2 in 78, stage 3 in 42, and stage 4
      in 4. The anteroposterior diameter had an excellent linear correlation (r =
      0.814; P < .001) with the hiatal area during the Valsalva maneuver and was
      strongly related to ICS POP-Q stages (P < .01). A receiver operating
      characteristic curve analysis proposed a cutoff of 6.0 cm for the anteroposterior
      diameter against ICS POP-Q stage 2 and higher (sensitivity, 73%; specificity,
      52%) and prolapse symptoms (sensitivity, 74%; specificity, 64%). CONCLUSIONS: The
      anteroposterior hiatal diameter, which represents hiatal distensibility in the
      midsagittal plane, can be used to evaluate hiatal ballooning. "Mild" ballooning
      was defined as an anteroposterior diameter measurement of 6.0 to less than 6.5
      cm, "moderate" ballooning as 6.5 to less than 7.0 cm, and "marked" ballooning as
      7.0 cm or greater.

PMID- 29027693
TI  - Efficacy and safety of golimumab in Crohn's disease: a French national
      retrospective study.
AB  - BACKGROUND: Anti-tumour necrosis factor (TNF) agents have improved the care of
      Crohn's disease (CD). After the first anti-TNF discontinuation, it is possible to
      switch to another anti-TNF. Three anti-TNF agents are available for ulcerative
      colitis (infliximab, adalimumab and golimumab), but only the first 2 have been
      approved for CD because golimumab has not been studied for this indication. AIM:
      To report the efficacy and safety of golimumab in CD. METHODS: Crohn's disease
      patients who received golimumab were identified in 12 French tertiary centres and
      were retrospectively analysed. The primary endpoint was the duration of golimumab
      treatment before escalation or discontinuation. The clinical response was defined
      as a decrease of more than 3 points in the Harvey-Bradshaw index or by global
      physician assessment. RESULTS: One hundred and fifteen patients were included.
      The golimumab treatment duration was 9.8 months (0.55-44), and 48.7% of the
      patients were still under treatment at the end of follow-up. Clinical response
      was observed in 55.8% of the patients after a mean duration of 3.8 months. The
      probability of remaining under treatment without escalation at 6, 12 and 24
      months was 54.6%, 34.9% and 19.3% respectively. In multivariate analysis,
      discontinuation of the first anti-TNF agent due to intolerance (odds ratio, OR =
      2.16; 95% CI, confidence interval [1.25-3.86]; P = .005) and co-immunosuppression
      for more than 6 months (OR = 3.98; 95% CI [2.3-7.1]; P < .0001) were predictive
      factors of efficacy. Six per cent of the patients discontinued treatment due to
      intolerance. CONCLUSION: After failure of infliximab or adalimumab for Crohn's
      disease, golimumab was safe and seemed beneficial in half of the patients.

PMID- 29027695
TI  - Shear Wave Elastographic Alterations in the Kidney After Extracorporeal Shock
      Wave Lithotripsy.
AB  - OBJECTIVES: Extracorporeal shock wave lithotripsy (ESWL) is a method used
      frequently for the treatment of renal stone disease. Although its safety is
      proven, there are still concerns about its unwanted effects on kidneys. In this
      prospective study, we aimed to evaluate renal tissue alterations with shear wave
      elastography (SWE) after ESWL. We also studied the correlation between SWE and
      resistive index (RI) changes. METHODS: The study included 59 patients who
      underwent ESWL treatment for renal stone disease. We performed SWE and color
      Doppler ultrasonography to calculate SWE and RI values before, 1 hour after, and
      1 week after lithotripsy treatment. A binary comparison was performed by the
      Bonferroni test. The correlation between SWE and RI values was evaluated by a
      Pearson correlation analysis. RESULTS: The patients included 26 women (44.1%) and
      33 men (55.9%). Their ages ranged from 20 to 65 years (mean +/- SD, 45.0 +/- 1.1
      years). Stone diameters ranged from 7 to 19 mm (mean, 13.0 +/- 0.5 mm). There was
      a significant difference in SWE values before and 1 hour after lithotripsy
      treatment (P = .001; P < .01). In the follow-up measurement 1 week after
      treatment, this difference disappeared (P > .99; P > .05). Resistive index values
      increased significantly 1 hour after lithotripsy treatment and returned to
      prelithotripsy values 1 week after treatment. In the correlation analysis, SWE
      and RI values were not correlated. CONCLUSIONS: Measurements of alterations in
      SWE values after ESWL can provide useful information about renal tissue injury.

PMID- 29027696
TI  - Computer-Aided Evaluation of Blood Vessel Geometry From Acoustic Images.
AB  - A method for computer-aided assessment of blood vessel geometries based on shape
      fitting algorithms from metric vision was evaluated. Acoustic images of cross
      sections of the radial artery and cephalic vein were acquired, and medical
      practitioners used a computer application to measure the wall thickness and
      nominal diameter of these blood vessels with a caliper method and the shape
      fitting method. The methods performed equally well for wall thickness
      measurements. The shape-fitting method was preferable for measuring the diameter,
      since it reduced systematic errors by up to 63% in the case of the cephalic vein
      because of its eccentricity.

PMID- 29027697
TI  - Development and validation of a reverse transcription quantitative polymerase
      chain reaction for tilapia lake virus detection in clinical samples and
      experimentally challenged fish.
AB  - Tilapia lake virus (TiLV) is an emerging pathogen associated with high
      mortalities of wild and farm-raised tilapia in different countries. In this
      study, a SYBR green-based reverse transcription quantitative polymerase chain
      reaction (RT-qPCR) assay targeting segment three of the virus was developed to
      detect and quantify TiLV in clinical samples and experimentally challenged fish.
      All 30 field samples with clinical signs and history consistent with TiLV
      infection were positive for TiLV as detected by the developed RT-qPCR method. The
      RT-qPCR technique provided 100 and 10,000 times more sensitive for virus
      detection than those offered by the RT-PCR and virus isolation in cell culture
      methods, respectively. The detection limit of the RT-qPCR method was as low as
      two viral copies/MUl. Moreover, the RT-qPCR technique could be applied for TiLV
      detection in various fish tissues including gills, liver, brain, heart, anterior
      kidney and spleen. Significantly, this study delivered an accurate and reliable
      method for rapid detection of TiLV viruses that facilitates active surveillance
      programme and disease containment.

PMID- 29027698
TI  - Buffalo heifers selected for lower residual feed intake have lower feed intake,
      better dietary nitrogen utilisation and reduced enteric methane production.
AB  - This study was conducted to evaluate the utilisation of the residual feed intake
      (RFI) as a feed efficiency selection tool and its relationship with methane
      emissions. Eighteen Murrah buffalo (Bubalus bubalis) heifers were fed ad libitum
      with total mixed ration (TMR) for 120 days. Based on linear regression models
      involving dry matter intake (DMI), average daily gain (ADG) and mid-test
      metabolic body size (MBW0.75 ), heifers were assigned into low and high RFI
      groups. The RFI varied from -0.09 to +0.12 kg DM/day with average RFI of -0.05
      and 0.05 kg DM/day in low and high RFI heifers respectively. Low RFI heifers ate
      11.6% less DM each day, yet average daily gain (ADG) and feed utilisation were
      comparable among low and high RFI groups. Low RFI heifers required significantly
      (p < .05) less metabolizable energy for maintenance (MEm) compared to high RFI
      heifers. Apparent nutrient digestibility showed non-significant difference (p >
      .05) among low and high RFI groups. Although the nitrogen balance was similar
      among heifers of low and high RFI groups, nitrogen metabolism was significantly
      higher (p > .05) in high RFI heifers. Comparison of data from heifers exhibiting
      the low (n = 9) and high (n = 9) RFI showed that the low RFI heifers have lower
      enteric methane production and methane losses than high RFI heifers. In
      conclusion, results of this study revealed that selection of more efficient
      buffalo heifers has multiple benefits, such as decreased feed intake and less
      emission of methane.

PMID- 29027699
TI  - Lymphopenia and fumaric acid esters for psoriasis: a retrospective case series
      prompted by the European Medicines Agency's Pharmacovigilance Risk Assessment
      Committee (PRAC) recommendations.

PMID- 29027700
TI  - Increases in the expression of Na+ /H+ exchanger 1 and 3 are associated with
      insulin signalling in the ruminal epithelium.
AB  - Na+ /H+ exchanger (NHE), which catalyses the exchange of extracellular Na+ for
      intracellular H+ , is of importance in the maintenance of Na+ and pH homoeostasis
      for rumen epithelial cells. Studies in ruminants showed that high concentrate
      diets could increase the expression of NHE in ruminal epithelium. Results of
      recent studies further indicated that insulin, as an important hormone closely
      related to dietary concentrate, could enhance the expression of NHE. In this
      study, we have investigated the mechanisms of insulin regulating the expression
      of NHE in rumen epithelial cells and its potential role in dietary modulation of
      NHE expression in ruminal epithelium of cows. In primary culture, insulin
      increased phosphorylation of ERK 1/2 and AKT in rumen epithelial cells. However,
      this promotion was diminished by insulin receptor inhibitor. Insulin also
      stimulated NHE1 and NHE3 expression. But this increase was suppressed by insulin
      receptor inhibitor, ERK inhibitor and AKT inhibitor. In the present animal
      experiment, NHE1 and NHE3 expression increased in rumen epithelium of cows
      ingesting a high concentrate diet (HC, 60% concentrate), accompanied by increased
      insulin concentration in plasma, compared to those feeding a low concentrate diet
      (LC, 20% concentrate). Furthermore, the phosphorylation of ERK1/2 and AKT was
      higher in the rumen epithelium of the HC group than those in the LC group.
      Collectively, these results indicate that diet-dependent change of NHE1 and NHE3
      abundance was mediated, at least in part, by plasma insulin through the ERK and
      AKT pathway.

PMID- 29027703
TI  - 31st Annual Meeting of the Austrian Society of Transplantation, Transfusion and
      Genetics - Austrotransplant 2017, Zell am See, Austria, 18-20 October 2017.

PMID- 29027701
TI  - Cellular and molecular characterization of IDH1-mutated diffuse low grade gliomas
      reveals tumor heterogeneity and absence of EGFR/PDGFRalpha activation.
AB  - Diffuse low grade gliomas (DLGG, grade II gliomas) are slowly-growing brain
      tumors that often progress into high grade gliomas. Most tumors have a missense
      mutation for IDH1 combined with 1p19q codeletion in oligodendrogliomas or
      ATRX/TP53 mutations in astrocytomas. The phenotype of tumoral cells, their
      environment and the pathways activated in these tumors are still ill-defined and
      are mainly based on genomics and transcriptomics analysis. Here we used freshly
      resected tumors to accurately characterize the tumoral cell population and their
      environment. In oligodendrogliomas, cells express the transcription factors MYT1,
      Nkx2.2, Olig1, Olig2, Sox8, four receptors (EGFR, PDGFRalpha, LIFR, PTPRZ1) but
      not the co-receptor NG2 known to be expressed by oligodendrocyte progenitor
      cells. A variable fraction of cells also express the more mature oligodendrocytic
      markers NOGO-A and MAG. DLGG cells are also stained for the young-neuron marker
      doublecortin (Dcx) which is also observed in oligodendrocytic cells in nontumoral
      human brain. In astrocytomas, MYT1, PDGFRalpha, PTPRZ1 were less expressed
      whereas Sox9 was prominent over Sox8. The phenotype of DLGG cells is overall
      maintained in culture. Phospho-array screening showed the absence of EGFR and
      PDGFRalpha phosphorylation in DLGG but revealed the strong activation of p44/42
      MAPK/ERK which was present in a fraction of tumoral cells but also in nontumoral
      cells. These results provide evidence for the existence of close relationships
      between the cellular phenotype and the mutations found in DLGG. The slow
      proliferation of these tumors may be associated with the absence of activation of
      PDGFRalpha/EGFR receptors.

PMID- 29027702
TI  - PER1, GUP1 and CWH43 of methylotrophic yeast Ogataea minuta are involved in cell
      wall integrity.
AB  - In eukaryotes, the glycosylphosphatidylinositol (GPI) modification of many
      glycoproteins on the cell surface is highly conserved. The lipid moieties of GPI
      anchored proteins undergo remodelling processes during their maturation. To date,
      the products of the PER1, GUP1 and CWH43 genes of the yeast Saccharomyces
      cerevisiae have been shown to be involved in the lipid remodelling. Here, we
      focus on the putative GPI remodelling pathway in the methylotrophic yeast Ogataea
      minuta. We found that the O. minuta homologues of PER1, GUP1 and CWH43 are
      functionally compatible with those of S. cerevisiae. Disruption of GUP1 or CWH43
      in O. minuta caused a growth defect under non-permissive conditions. The O.
      minuta per1Delta mutant exhibited a more fragile phenotype than the gup1Delta or
      cwh43Delta mutants. To address the role of GPI modification in O. minuta, we
      assessed the effect of these mutations on the processing and localization of the
      O. minuta homologues of the Gas1 protein; in S. cerevisiae, Gas1p is an abundant
      and well-characterized GPI-anchored protein. We found that O. minuta possesses
      two copies of the GAS1 gene, which we designate GAS1A and GAS1B. Microscopy and
      western blotting analysis showed mislocalization and/or lower retention of Gas1Ap
      and Gas1Bp within the membrane fraction in per1Delta or gup1Delta mutant cells,
      suggesting the significance of lipid remodelling for GPI-anchored proteins in O.
      minuta. Localization behaviour of Gas1Bp differed from that of Gas1Ap. Our data
      reveals, for the first time (to our knowledge), the existence of genes related to
      GPI anchor remodelling in O. minuta cells.

PMID- 29027704
TI  - Effect of Royal Jelly on behavioural patterns, feather quality, egg quality and
      some haematological parameters in laying hens at the late stage of production.
AB  - The aim was to elucidate the impact of Royal Jelly (RJ) on behavioural patterns,
      feather cover, egg quality and some blood haematological indices in laying hens
      (58-64 weeks of age). A total of 108 Tetra Brown laying hens were used in the
      current trial. The birds were divided into three equal groups (36 birds each).
      The pure RJ was prepared for immediate injection subcutaneously, as follows: the
      first treated group (RJ1 :100 mg/kg); the second treated group (RJ2 :200 mg/kg);
      the control group. The eating and drinking activities in the RJ2 group were
      significantly (p = .009 and .015 respectively) higher than the control and RJ1
      groups. Furthermore, the aggressive pecks, feather pecks and threating behaviour
      in the RJ2 group were significantly (p = .005, .001 and .039 respectively) lower
      than the control and RJ1 groups. Both RJ-treated groups had the best feather
      cover on the neck and abdomen regions (p = .010 and .001 respectively; Figure ).
      Both RJ-treated groups had a significantly higher eggshell ratio (p = .019) and
      shell thickness (p = .001) in comparison with the control group. The albumen
      height, Haugh units and yolk index in both RJ-treated groups were significantly
      greater than those recorded in the control group (p = .026, .001 and .022
      respectively). The erythrocyte and total leucocyte counts in the RJ2 group were
      significantly higher than those reported in the control and RJ1 groups (p = .029
      and .013 respectively); however, the heterophil/lymphocyte (H/L) ratio and
      heterophil % in both RJ-treated groups were significantly the lowest (p = .001
      and .039). In conclusion, birds in the RJ2 group had superior feather cover,
      welfare and behavioural indices, probably due to the impact of active flavonoids
      components of RJ on laying hen performance. Furthermore, the RJ-treated groups
      had significantly improved egg quality parameters and some blood haematological
      indices.

PMID- 29027705
TI  - Effects of dietary supplementation of spices on forage degradability, ruminal
      fermentation, in vivo digestibility, growth performance and nitrogen balance in
      Black Bengal goat.
AB  - The objective of the study was to evaluate the effects of spices on forage
      utilization and nitrogen (N) emission using in vitro and in vivo approach. A 6 *
      5 factorial triplicate arrangement was used to assess the in vitro degradability
      of rice straw with control (without spices) and individual (40 mg/g rice straw)
      spices (cumin, coriander, clove, black cumin, turmeric) at five different
      incubation times. In vitro dry matter (DM) and organic matter (OM) degradability
      of rice straw were highest in presence of spices except for clove. Clove
      significantly reduced the total volatile fatty acids concentration, molar
      proportion of acetate and propionate ratio, but increased propionate production.
      Acetate and butyrate production were not affected by treatments. The ammonia
      nitrogen concentration was lowest for clove and turmeric compared to other
      spices. Rumen pH was unchanged but gradually decreased over the incubation
      period. For in vivo study, 12 bucks with average live weight 7.65 +/- 0.19 kg
      were assigned to a completely randomized design with three treatments and four
      replicates for a 28-day period. Bucks were fed a total mixed ration without (0
      g/kg DM) or with (2.5, 7.5 g/kg DM) clove supplementation. DM intake, body weight
      and apparent total tract digestibility of crude protein (CP) and acid detergent
      fibre (ADF) were not affected by increasing dietary doses of clove but tended (p
      = .09) to increase DM and OM digestibility. The urinary N and urine urea N
      concentration of bucks decreased linearly with incremental doses of clove diet.
      In contrary, clove supplementation had positive effects on plasma urea N and
      retained N in bucks. We concluded that though some spices had positive effects on
      ruminal digestion and fermentation, the dosage level assessed in the current
      study (up to 7.5 g/kg DM clove) can be promoted as an effective dietary approach
      to mitigate N losses in bucks.

PMID- 29027706
TI  - Regional citrate anticoagulation with calcium replacement in pediatric apheresis.
AB  - PURPOSE: The objective of this retrospective analysis was to present our single
      center experience with intravenous (IV) calcium replacement and regional citrate
      anticoagulation in pediatric apheresis therapy with the aim of developing a
      standard operating procedure to minimize symptomatic hypocalcemia. METHODS: We
      analyzed apheresis procedures in patients <18 years of age over a 2-year time
      period (Jan 2012 to Dec 2014). Procedures in tandem with other extracorporeal
      therapies, including continuous renal replacement therapy, extracorporeal liver
      support, and extracorporeal membrane oxygenation, were excluded. RESULTS: Two
      hundred and six patients underwent 1176 procedures. All procedures were performed
      with acid citrate dextrose formula A (ACD-A) for anticoagulation and IV calcium
      replacement. The majority of procedures (56.7%) were therapeutic plasma exchange
      (TPE). The average rate of IV calcium chloride (2.16 mg/mL of elemental calcium)
      was 60.4 +/- 21.4 mL/h while inlet flow rate was 43.7 +/- 16.3 mL/min. Patients
      experienced hypocalcemia in 63 of 1176 procedures (5.3%), including 48 episodes
      (4.1%) of hypocalcemia during apheresis treatment. Two procedures with
      hypocalcemia had symptoms: one slight lip twitch and one patient with abdominal
      pain. No hemodynamic alterations were noted in any procedure associated with
      hypocalcemia. Hypocalcemia was seen the least with RCE. For patients with
      hypocalcemia prior to the apheresis session, we used a calcium infusion running
      at 1.6 times the inlet flow rate. CONCLUSION: Running IV calcium at 1.4 times the
      inlet flow rate resulted in a lower incidence of hypocalcemia than reported in
      literature describing other approaches to apheresis. It nearly eliminated
      episodes of symptomatic hypocalcemia.

PMID- 29027707
TI  - A Trichosporonales genome tree based on 27 haploid and three evolutionarily
      conserved 'natural' hybrid genomes.
AB  - To construct a backbone tree consisting of basidiomycetous yeasts, draft genome
      sequences from 25 species of Trichosporonales (Tremellomycetes, Basidiomycota)
      were generated. In addition to the hybrid genomes of Trichosporon coremiiforme
      and Trichosporon ovoides that we described previously, we identified an
      interspecies hybrid genome in Cutaneotrichosporon mucoides (formerly Trichosporon
      mucoides). This hybrid genome had a gene retention rate of ~55%, and its closest
      haploid relative was Cutaneotrichosporon dermatis. After constructing the C.
      mucoides subgenomes, we generated a phylogenetic tree using genome data from the
      27 haploid species and the subgenome data from the three hybrid genome species.
      It was a high-quality tree with 100% bootstrap support for all of the branches.
      The genome-based tree provided superior resolution compared with previous multi
      gene analyses. Although our backbone tree does not include all Trichosporonales
      genera (e.g. Cryptotrichosporon), it will be valuable for future analyses of
      genome data. Interest in interspecies hybrid fungal genomes has recently
      increased because they may provide a basis for new technologies. The three
      Trichosporonales hybrid genomes described in this study are different from well
      characterized hybrid genomes (e.g. those of Saccharomyces pastorianus and
      Saccharomyces bayanus) because these hybridization events probably occurred in
      the distant evolutionary past. Hence, they will be useful for studying genome
      stability following hybridization and speciation events. Copyright (c) 2017 John
      Wiley & Sons, Ltd.

PMID- 29027708
TI  - Advancing Prenatal Detection of Congenital Heart Disease: A Novel Screening
      Protocol Improves Early Diagnosis of Complex Congenital Heart Disease.
AB  - OBJECTIVES: Prenatal diagnosis of complex congenital heart disease (CHD) during
      routine obstetric ultrasound (US) examinations improves postnatal outcomes, but
      sensitivity is low (<40%). Our objective was to improve our prenatal detection of
      complex CHD with implementation of a specific screening protocol. METHODS: From
      January 2003 to December 2013, 506 consecutive confirmed cases of complex CHD in
      the province of Manitoba, Canada, were analyzed to compare the sensitivity and
      positive predictive value of prenatal US detection of complex CHD before and
      after the introduction of a novel prenatal screening protocol. The intervention
      was done in October 2004, emphasizing screening and not diagnosis of complex CHD.
      It involved education, practical scanning tips, a checklist, and feedback on
      cases. We also assessed the effect of the intervention in different screening
      settings: community hospitals, tertiary hospitals, and fetal assessment units.
      RESULTS: The sensitivity for detecting complex CHD increased from 29.8% to 88.3%
      (P < .0001), while the positive predictive value remained high. The largest
      improvement in detection was found for US units in community hospitals (52.4%
      higher; P < .0001), followed by tertiary hospitals (39.9%; P = .0004), and fetal
      assessment units (7.2%; P = .16). Additionally, there was a significant decrease
      in the presentation of neonates in critical condition from before to after the
      implementation (24.3% to 13.1%, respectively; P = .0165). CONCLUSIONS:
      Implementing a focused routine prenatal screening protocol can vastly improve
      detection rates of critical cardiac abnormalities. The improvement in community
      hospitals was particularly important because early detection ensured that the
      birth was planned to take place in an appropriate facility. Our novel protocol
      can be performed by all sonographers, regardless of experience, equipment used,
      and hospital setting.

PMID- 29027709
TI  - Pemphigus vulgaris complicated by extensive keloid scarring.

PMID- 29027710
TI  - Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome: An Unusual In Utero
      Presentation.

PMID- 29027711
TI  - Expansion of mesenchymal stem cells on electrospun scaffolds maintains stemness,
      mechano-responsivity, and differentiation potential.
AB  - Mesenchymal stem cells (MSCs) hold great promise for regenerative therapies and
      tissue engineering applications given their multipotential differentiation
      capacity. However, MSC isolation and expansion are typically performed on super
      physiologically stiff tissue culture plastic (TCP), which may alter their
      behavior and lead to unintended consequences upon implantation. In contrast,
      electrospun nanofibrous scaffolds possess physical and mechanical properties that
      are similar to that of native tissue. In this study, we investigated whether
      isolation and expansion of juvenile bovine MSCs directly onto electrospun
      nanofibrous scaffolds better preserves MSC phenotype and stemness compared to
      TCP. Our data show that culture of MSCs on electrospun scaffolds reduces
      proliferation, decreases cellular senescence, and better maintains stemness
      compared to cells isolated and expanded on TCP, likely due to a reduction in cell
      contractility. Furthermore, in contrast to electrospun scaffolds, TCP biased MSCs
      towards a fibrotic phenotype that persisted even after the cells were reseeded
      onto a different substrate. Cells pre-cultured on electrospun scaffolds exhibited
      a heightened response to mechanical stimuli and greater chondrogenesis in
      methacrylated hyaluronic acid hydrogels. These data suggest that alternative
      substrates that better approximate the native cell environment should be used to
      preserve endogenous MSC behavior and may improve their success in tissue
      engineering applications. (c) 2017 Orthopaedic Research Society. Published by
      Wiley Periodicals, Inc. J Orthop Res 36:808-815, 2018.

PMID- 29027712
TI  - Upregulation of UBE2Q1 via gene copy number gain in hepatocellular carcinoma
      promotes cancer progression through beta-catenin-EGFR-PI3K-Akt-mTOR signaling
      pathway.
AB  - Hepatocellular carcinoma (HCC) is the most common type of liver cancer and
      represents a highly malignant tumor with a poor prognosis. Therapeutic modalities
      for HCC are limited and generally ineffective. UBE2Q1 is a putative E2 ubiquitin
      conjugating enzyme, and has been shown to be overexpressed in various types of
      cancers including HCC. How UBE2Q1 contributes to hepatocarcinogenesis remains
      unknown. Here, we show that UBE2Q1 is up-regulated in HCC cell lines and in a
      subset of human HCC tissues. Up-regulation of UBE2Q1 in primary HCC tumors was
      significantly correlated with shorter overall survival and disease-free survival.
      Mechanistically, we showed that the frequent up-regulation of UBE2Q1 in HCCs was
      attributed to the recurrent UBE2Q1 gene copy gain at chromosome 1q21.
      Functionally, we showed that knockdown of UBE2Q1 reduced HCC cell proliferation,
      promoted apoptosis via induction of GADD45alpha, and suppressed orthotopic
      tumorigenicity both in vitro and in vivo. Inactivation of UBE2Q1 also impeded HCC
      cell migration and invasion in vitro through regulating EMT process, and
      suppressed HCC metastasis in vivo. Interestingly, our data revealed a role of
      UBE2Q1 in the regulation of beta-catenin-EGFR-PI3K-Akt-mTOR signaling pathway.
      Our findings indicate that UBE2Q1 is a candidate oncogene involved in HCC
      development and progression and therefore a potential therapeutic target in
      applicable HCC patients.

PMID- 29027714
TI  - Practical Synthesis of alpha-Amyrin, beta-Amyrin, and Lupeol: The Potential
      Natural Inhibitors of Human Oxidosqualene Cyclase.
AB  - A practical synthesis of alpha-amyrin (1), beta-amyrin (2), and lupeol (3) was
      accomplished in total yields of 32, 42, and 40% starting from easily available
      ursolic acid (4), oleanolic acid (5), and betulin (6), respectively. Remarkably,
      these three natural pentacyclic triterpenes exhibited potential inhibitory
      activity against human oxidosqualene cyclase.

PMID- 29027713
TI  - Engineering Cell Surface Function with DNA Origami.
AB  - A specific and reversible method is reported to engineer cell-membrane function
      by embedding DNA-origami nanodevices onto the cell surface. Robust membrane
      functionalization across epithelial, mesenchymal, and nonadherent immune cells is
      achieved with DNA nanoplatforms that enable functions including the construction
      of higher-order DNA assemblies at the cell surface and programed cell-cell
      adhesion between homotypic and heterotypic cells via sequence-specific DNA
      hybridization. It is anticipated that integration of DNA-origami nanodevices can
      transform the cell membrane into an engineered material that can mimic,
      manipulate, and measure biophysical and biochemical function within the plasma
      membrane of living cells.

PMID- 29027715
TI  - Diagnostic performance of human epididymis protein 4 compared to a combination of
      biophysical and biochemical markers to differentiate ovarian endometriosis from
      epithelial ovarian cancer in premenopausal women.
AB  - AIM: This study is a comparison of human epididymis protein 4 (HE4) with cancer
      antigen 125 (CA125), using the Risk of Ovarian Malignancy Algorithm (ROMA),
      Copenhagen Index (CPH-I), Risk of Malignancy Index (RMI) and Morphology Index
      (MI) to differentiate ovarian endometriosis from epithelial ovarian cancer (EOC)
      in premenopausal women. METHODS: The study was performed at the University Clinic
      of Obstetrics and Gynecology in Skopje. One hundred and sixty-four premenopausal
      patients were divided into three study groups, including ovarian endometriosis
      (37), other benign pelvic masses (57) and EOCs (11), and a control group (59).
      After ultrasonography, all subjects underwent blood sampling. Surgery and
      histological verification was performed. Pelvic masses were classified based on
      histological findings. Mann-Whitney, receiver operating characteristic-area under
      the curve (AUC), sensitivity, specificity and Kruskal-Wallis tests were used for
      statistical analysis. The level of significance alpha was set at 5%. RESULTS: For
      each of the tested markers, sensitivity, specificity and accuracy to distinguish
      ovarian endometriosis from EOC were as follows: HE4 (81.82%, 100%, 95.83%); CA125
      (81.82%, 48.65%, 56.25%); ROMA (90.91%, 83.78%, 85.42%); CPH-I (81.82%, 97.30%,
      93.75%); RMI (90.91%, 35.14%, 47.92%); and MI (100%, 75.68%, 81.25%),
      respectively. The AUC for ovarian endometriosis compared to EOC for tested
      markers was as follows: HE4 (AUC = 0.934), CA125 (AUC = 0.821), ROMA (AUC =
      0.929), CPH-I (AUC = 0.924) and RMI (AUC = 0.880), respectively. CONCLUSION: HE4
      and CPH-I perform best to discriminate ovarian endometriosis from EOC in
      premenopausal women. MI has maximal sensitivity to detect EOC.

PMID- 29027716
TI  - Cytotoxicity of Group 5 Transition Metal Ditellurides (MTe2 ; M=V, Nb, Ta).
AB  - Much research effort has been put in to study layered compounds with transition
      metal dichalcogenides (TMDs) being one of the most studied compounds. Due to
      their extraordinary properties such as excellent electrochemical properties,
      tuneable band gaps, and low shear resistance due to weak van der Waals
      interactions between layers, TMDs have been found to have wide applications such
      as electrocatalysts for hydrogen evolution reactions, supercapacitors,
      biosensors, field-effect transistors (FETs), photovoltaics, and lubricant
      additives. In very recent years, Group 5 transition metal ditellurides have
      received an immense amount of research attention. However to date, little has
      been known of the potential toxicities posed by these materials. As such, we
      conducted the cytotoxicity study by incubating various concentrations of the
      Group 5 transition metal ditellurides (MTe2 ; M=V, Nb, Ta) with human lung
      carcinoma epithelial A549 cells for 24 hours and the remaining cell viabilities
      after treatment was measured. Our findings indicate that VTe2 is highly toxic
      whereas NbTe2 and TaTe2 are deemed to exhibit mild toxicities. This study
      constitutes an exemplary first step towards the understanding of the Group 5
      transition metal ditellurides' toxicity effects in preparation for their possible
      future commercialisation.

PMID- 29027717
TI  - Functional characterization of five NR5A1 gene mutations found in patients with
      46,XY disorders of sex development.
AB  - Steroidogenic factor-1 (SF1), encoded by the NR5A1 gene, is a key regulator of
      steroidogenesis and reproductive development. NR5A1 mutations described in 46,XY
      patients with disorders of sex development (DSD) can be associated with a range
      of conditions of phenotypes; however, the genotype-phenotype correlation remains
      elusive in many cases. In the present study, we describe the impact of five NR5A1
      variants (three novel: p.Arg39Cys, p.Ser32Asn, and p.Lys396Argfs*34; and two
      previously described: p.Cys65Tyr and p.Cys247*) on protein function, identified
      in seven patients with 46,XY DSD. In vitro functional analyses demonstrate that
      NR5A1 mutations impair protein functions and result in the DSD phenotype observed
      in our patients. Missense mutations in the DNA binding domain and the frameshift
      mutation p.Lys396Argfs*34 lead to both, markedly affected transactivation assays,
      and loss of DNA binding, whereas the mutation p.Cys247* retained partial
      transactivation capacity and the ability to bind a consensus SF1 responsive
      element. SF1 acts in a dose-dependent manner and regulates a cascade of genes
      involved in the sex determination and steroidogenesis, but in most cases reported
      so far, still lead to a sufficient adrenal steroidogenesis and function, just
      like in our cases, in which heterozygous mutations are associated to 46,XY DSD
      with intact adrenal steroid biosynthesis.

PMID- 29027718
TI  - Hypervascular retained product of conception: Characteristic magnetic resonance
      imaging and possible relationship to placental polyp and pseudoaneurysm.
AB  - The cases of two patients who developed myometrial vascularization following
      dilatation and curettage are described. In case 1, pathological diagnosis was
      possible with the resected specimens. This patient had hypervascular retained
      products of conception (RPOC). In case 2, the natural course of this pathological
      condition was observed, confirming a process of regression during repeated
      withdrawal bleeding. The three principal magnetic resonance imaging (MRI)
      findings in these cases were: (i) presence of a remnant; (ii) breaking of the
      junctional zone in contact with the remnant; and (iii) vascularization/flow voids
      infiltrating into the myometrium from the broken junctional zone. These three MRI
      findings differed in degree and varied in combination in each case of RPOC.
      Uterine artery pseudoaneurysms have been reported as intrauterine vascularization
      after abortion or delivery with subsequent spontaneous regression. These reports
      may include cases of hypervascular RPOC.

PMID- 29027719
TI  - Glioplasticity in irritable bowel syndrome.
AB  - BACKGROUND: Growing evidence indicates a wide array of cellular remodeling in the
      mucosal microenvironment during irritable bowel syndrome (IBS), which possibly
      contributes to pathophysiology and symptom generation. Here, we investigated
      whether enteric glial cells (EGC) may be altered, and which factors/mechanisms
      lead to these changes. METHODS: Colonic mucosal biopsies of IBS patients (13 IBS
      Constipation [IBS-C]; 10 IBS-Diarrhea [IBS-D]; 11 IBS-Mixed [IBS-M]) and 24
      healthy controls (HC) were analyzed. Expression of S100beta and GFAP was
      measured. Cultured rat EGC were incubated with supernatants from mucosal
      biopsies, then proliferation and Ca2+ response to ATP were analyzed using flow
      cytometry and Ca2+ imaging. Histamine and histamine 1-receptor (H1R) involvement
      in the effects of supernatant upon EGC was analyzed. KEY RESULTS: Compared to HC,
      the mucosal area immunoreactive for S100beta was significantly reduced in
      biopsies of IBS patients, independently of the IBS subtype. IBS-C supernatants
      reduced EGC proliferation and IBS-D and IBS-M supernatants reduced Ca2+ response
      to ATP in EGC. EGC expressed H1R and the effects of supernatant upon Ca2+
      response to ATP in EGC were blocked by pyrilamine and reproduced by histamine via
      H1R. IBS supernatants reduced mRNA expression of connexin-43. The S100beta
      stained area was negatively correlated with the frequency and intensity of pain
      and bloating. CONCLUSION AND INFERENCES: Changes in EGC occur in IBS, involving
      mucosal soluble factors. Histamine, via activation of H1R-dependent pathways,
      partly mediates altered Ca2+ response to ATP in EGC. These changes may contribute
      to the pathophysiology and the perception of pain and bloating in patients with
      IBS.

PMID- 29027720
TI  - The effect of different thermal treatment on the physical properties of PGA/PCL
      copolymer suture material.
AB  - Samples of polyglycolic acid PGA/polycaprolactone PCL copolymer absorbable suture
      materials, which is called Poliglecaprone PGC copolymer suture, were thermally
      treated by two different processes. The first method is the direct heat exposure,
      from 20 to 38  degrees C, in the surrounding medium. Which is an environmental
      study. The other method is the annealing process at temperatures ranged from 65,
      80, 100, 120, and 140  degrees C, for two different duration periods 60 and 120
      min. This is an extensive technical study. The refractive indices of thermally
      treated PGA/PCL copolymer sutures were measured using multiple-beam Fizeau
      fringes. The birefringence profiles across the suture cross-sections were studied
      for different annealing conditions. The effect of heat on the polarizabilty per
      unit volume, dielectric properties, and suture diameter were investigated. The
      activation energy for the heating processes was calculated using Arrhenius
      equation. Microinterferograms are given for illustration.

PMID- 29027721
TI  - N-Doped Carbon Nanofibrous Network Derived from Bacterial Cellulose for the
      Loading of Pt Nanoparticles for Methanol Oxidation Reaction.
AB  - The large-scale, low-cost preparation of Pt-based catalysts with high activity
      and durability for the methanol oxidation reaction is still challenging. The key
      to achieving this aim is finding suitable supporting materials. In this paper, N
      doped carbon nanofibrous networks are prepared by annealing a gel containing two
      inexpensive and ecofriendly precursors, that is, bacterial cellulose and urea,
      for the loading of Pt nanoparticles. An undoped analogue is also prepared for
      comparison. Meanwhile, the effect of the annealing temperature on the performance
      of the catalysts is evaluated. The results show that the N doping and higher
      annealing temperature can improve the electron conductivity of the catalyst and
      provide more active sites for the loading of ultrafine Pt nanoparticles with a
      narrow size distribution. The best catalyst exhibits a remarkably high
      electrocatalytic activity (627 mA mg-1 ), excellent poison tolerance, and high
      durability. This work demonstrates an ideal Pt supporting material for the
      methanol oxidation reaction.

PMID- 29027722
TI  - The Coordination and Supramolecular Chemistry of Gold Metalloligands.
AB  - This review article deals with the use of gold metalloligands as building blocks
      for the assembly of heterometallic complexes. Several families of gold complexes
      decorated with crown-ether, amide, pyridine, bipyridine, terpyridine,
      carboxylato, amino acid or pi-alkyne binding sites have been reported. Adducts of
      these metalloligands with alkaline or transition-metal cations, or with
      transition-metal or lanthanide complexes, have been isolated and structurally
      characterized. The reported heterometallic species range from simple dinuclear
      complexes to self-assembled supramolecules, coordination polymers, or solids. New
      structural motifs have been found in these complexes. Most of these
      metalloligands and complexes are photoluminescent and some of them show
      switchable emissions based on the formation and rupture of metallophilic
      contacts. Potential applications as sensors, sensitizers, in vivo imaging agents,
      and anticancer drugs are envisaged.

PMID- 29027724
TI  - Adsorbed Eutectic GaIn Structures on a Neoprene Foam for Stretchable MRI Coils.
AB  - Stretchable conductors based on eutectic gallium-indium (eGaIn) alloy are
      patterned on a polychloroprene substrate (neoprene foam) using stencil printing.
      By tuning the amount of eGaIn on the neoprene substrate, different strain
      sensitivity of electrical resistance is achieved. Conductors with a layer of
      eGaIn, which adsorbs to the walls of 60-100 um wide neoprene cells, change their
      electrical resistance for 5% at 100% strain. When the amount of eGaIn is
      increased, the cells are filled with eGaIn and the strain-sensitivity of the
      electrical resistance rises to 300% at 100% strain. The developed conductors are
      patterned as stretchable on-body coils for receiving magnetic signals in a
      clinical magnetic resonance imaging setup. First images with a stretchable coil
      are acquired on an orange and compared to the images that are recorded using a
      rigid copper coil of the same size.

PMID- 29027723
TI  - Diagnostic yield of chromosomal microarray analysis in fetuses with isolated
      increased nuchal translucency: a French multicenter study.
AB  - OBJECTIVE: To determine the frequency and nature of copy number variants (CNVs)
      identified by chromosomal microarray analysis (CMA) in a large cohort of fetuses
      with isolated increased nuchal translucency thickness (NT) >= 3.5 mm. METHODS:
      This was a retrospective, multicenter study, including 11 French hospitals, of
      data from the period between April 2012 and December 2015. In total, 720 fetuses
      were analyzed by rapid aneuploidy test and the fetuses identified as euploid
      underwent CMA. CNVs detected were evaluated for clinical significance and
      classified into five groups: pathogenic CNVs; benign CNVs; CNVs predisposing to
      neurodevelopmental disorders; variants of uncertain significance (VOUS); and CNVs
      not related to the phenotype (i.e. incidental findings). RESULTS: In 121 (16.8%)
      fetuses, an aneuploidy involving chromosome 13, 18 or 21 was detected by rapid
      aneuploidy test and the remaining 599 fetuses were euploid. Among these, 53
      (8.8%) had a CNV detected by CMA: 16/599 (2.7%) were considered to be pathogenic,
      including 11/599 (1.8%) that were cryptic (not visible by karyotyping); 7/599
      (1.2%) were CNVs predisposing to neurodevelopmental disorders; and 8/599 (1.3%)
      were VOUS. Additionally, there was one (0.2%) CNV that was unrelated to the
      reason for referral diagnosis (i.e. an incidental finding) and the remaining 21
      were benign CNVs, without clinical consequence. Interestingly, we identified five
      genomic imbalances of the 1q21.1 or 15q11.2 regions known to be associated with
      congenital heart defects. CONCLUSION: Our study demonstrates the benefit of CMA
      in the etiological diagnosis of fetuses with isolated increased NT. It is worth
      noting that most (69%) of the detected pathogenic CNVs were cryptic. Copyright
      (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 29027725
TI  - Severity of ineffective esophageal motility is associated with utilization of
      skeletal muscle relaxant medications.
AB  - BACKGROUND: Ineffective esophageal motility (IEM) is the most common finding on
      high-resolution esophageal manometry (HREM). The underlying mechanisms for IEM
      remain to be fully elucidated. The aim of this study was to determine if
      utilization of skeletal muscle relaxants is associated with IEM, and with more
      severe subtypes of the disorder. METHODS: Patients with diagnosis of IEM were
      gender and age matched to patients with normal HREM. Demographic information,
      symptoms, endoscopic findings, medication usage and medical comorbidities were
      recorded. Patients with a diagnosis of IEM were divided into subgroups based on
      mean distal contractile integral (DCI) and percentage of ineffective swallows,
      and assessed for clinically significant differences among patients with varying
      severity of underlying IEM. KEY RESULTS: A total of 118 patients were included in
      each group. There were no significant clinical differences between the group of
      patients with IEM and the group of patients with normal manometry. Within the
      group of IEM patients, those with mean DCI < 250 mm Hg/s/cm were more likely to
      be prescribed skeletal muscle relaxants (27.8% vs 11.0%, P = .044), and those
      using skeletal muscle relaxants had a larger mean percentage of ineffective
      swallows (81.1% vs 71.5%, P = .029). There were no significant differences across
      mean DCI subgroups in usage of any other medication, or in any of the demographic
      variables or disease comorbidities examined in this study. CONCLUSIONS &
      INFERENCES: Use of skeletal muscle relaxants is associated with more severe IEM,
      which may suggest a causal association between this class of medications and
      weaker esophageal peristalsis.

PMID- 29027726
TI  - Melanotic neuroectodermal tumour of infancy: An enigmatic tumour with unique
      cytomorphological features.

PMID- 29027727
TI  - Downregulated apoptosis and autophagy after anti-Abeta immunotherapy in
      Alzheimer's disease.
AB  - Abeta immunization of Alzheimer's disease (AD) patients in the AN1792 (Elan
      Pharmaceuticals) trial caused Abeta removal and a decreased density of neurons in
      the cerebral cortex. As preservation of neurons may be a critical determinant of
      outcome after Abeta immunization, we have assessed the impact of previous Abeta
      immunization on the expression of a range of apoptotic proteins in post-mortem
      human brain tissue. Cortex from 13 AD patients immunized with AN1792 (iAD) and
      from 27 nonimmunized AD (cAD) cases was immunolabeled for proapoptotic proteins
      implicated in AD pathophysiology: phosphorylated c-Jun N-terminal kinase (pJNK),
      activated caspase3 (a-casp3), phosphorylated GSK3beta on tyrosine 216
      (GSK3betatyr216 ), p53 and Cdk5/p35. Expression of these proteins was analyzed in
      relation to immunization status and other clinical data. The antigen load of all
      of these proapoptotic proteins was significantly lower in iAD than cAD (P <
      0.0001). In cAD, significant correlations (P < 0.001) were observed between:
      Cdk5/p35 and GSK3betatyr216 ; a-casp3 and Abeta42 ; p53 and age at death. In iAD,
      significant correlations were found between GSK3betatyr216 and a-casp3; both
      spongiosis and neuritic curvature ratio and Abeta42 ; and Cdk5/p35 and Abeta
      antibody level. Although neuronal loss was increased by immunization with AN1792,
      our present findings suggest downregulation of apoptosis in residual neurons and
      other cells.

PMID- 29027728
TI  - Hepatitis in AIDS patients.
AB  - The individuals with HIV infection are more susceptible to develop coinfections
      with infectious pathogens such as HCV and HBV. The routes of transmission of
      these pathogens are the same including sexual contact, injection drug use, or at
      birth from mother to an infant. The main reason of morbidity and mortality in HIV
      infected individuals is a liver disease in the context of antiretroviral therapy,
      and coinfection such as HCV and HBV complicates this condition. Nucleos(t)ide
      analogues are used for HBV infection management, and treatment of HCV infection
      is done by PegIFN and ribavirin combination and protease inhibitors. In this
      review, we focused on hepatitis B and C infections in HIV patients along with
      their therapies.

PMID- 29027729
TI  - Application of Bayesian analysis to the doubly labelled water method for total
      energy expenditure in humans.
AB  - RATIONALE: The doubly labelled water (DLW) method is the reference method for the
      estimation of free-living total energy expenditure (TEE). In this method, where
      both 2 H and 18 O are employed, different approaches have been adopted to deal
      with the non-conformity observed regarding the distribution space for the labels
      being non-coincident with total body water. However, the method adopted can have
      a significant effect on the estimated TEE. METHODS: We proposed a Bayesian
      reasoning approach to modify an assumed prior distribution for the space ratio
      using experimental data to derive the TEE. A Bayesian hierarchical approach was
      also investigated. The dataset was obtained from 59 adults (37 women) who
      underwent a DLW experiment during which the 2 H and 18 O enrichments were
      measured using isotope ratio mass spectrometry (IRMS). RESULTS: TEE was estimated
      at 9925 (9106-11236) [median and interquartile range], 9646 (9167-10540), and
      9,638 (9220-10340) kJ.day-1 for women and at 13961 (12851-15347), 13353 (12651
      15088) and 13211 (12653-14238) kJ.day-1 for men, using normalized non-Bayesian,
      independent Bayesian and hierarchical Bayesian approaches, respectively. A
      comparison of hierarchical Bayesian with normalized non-Bayesian methods
      indicated a marked difference in behaviour between genders. The median difference
      was -287 kJ.day-1 for women, and -750 kJ.day-1 for men. In men there is an
      appreciable compression of the TEE distribution obtained from the hierarchical
      model compared with the normalized non-Bayesian methods (range of TEE 11234-15431
      kJ.day-1 vs 10786-18221 kJ.day-1 ). An analogous, yet smaller, compression is
      seen in women (7081-12287 kJ.day-1 vs 6989-13775 kJ.day-1 ). CONCLUSIONS: The
      Bayesian analysis is an appealing method to estimate TEE during DLW experiments.
      The principal advantages over those obtained using the classical least-squares
      method is the generation of potentially more useful estimates of TEE, and
      improved handling of outliers and missing data scenarios, particularly if a
      hierarchical model is used.

PMID- 29027730
TI  - Psychological distress in post-partum women after non-invasive prenatal testing
      (NIPT) in Japan.
AB  - AIM: The purpose of this study was to clarify the characteristics of
      psychological mental distress in post-partum women after non-invasive prenatal
      testing (NIPT) in Japan. METHODS: Psychological mental distress was assessed
      using the Kessler Psychological Distress Scale (K6). We compared patients with
      (i) low pre-NIPT K6 and low post-partum K6 scores (control group), and (ii) low
      pre-NIPT K6 and a high post-partum K6 scores (case group). RESULTS: Among the 697
      women who underwent NIPT, 29 (4.2%) had low pre-NIPT K6 and high post-partum K6
      scores (case group) and 668 (95.8%) had low pre-NIPT K6 and low post-partum K6
      scores (control). Among women with negative NIPT findings, post-partum women with
      a high K6 score were compared to a control group of women with a low K6 score.
      Logistic regression analysis showed that primiparity (P = 0.007), low birthweight
      (P = 0.005) and use of intracytoplasmic sperm injection (P = 0.02) and assisted
      reproductive technology (P = 0.05) were significantly different between the
      groups. CONCLUSION: Even if women do not feel mental distress before NIPT, they
      may develop mental stress post-partum. In particular, primipara women who
      conceived through assisted reproductive technology (especially intracytoplasmic
      sperm injection) and gave birth to a low birthweight baby were more susceptible
      to developing post-partum distress. Thus, it is important to educate women that
      support is available, with consultation with other healthcare professionals
      during genetic counseling if necessary. Further studies are needed in order to
      determine the factors associated with post-partum mental distress.

PMID- 29027731
TI  - High-Performance Inorganic Perovskite Quantum Dot-Organic Semiconductor Hybrid
      Phototransistors.
AB  - All-inorganic lead halide perovskite quantum dots (IHP QDs) have great potentials
      in photodetectors. However, the photoresponsivity is limited by the low charge
      transport efficiency of the IHP QD layers. High-performance phototransistors
      based on IHP QDs hybridized with organic semiconductors (OSCs) are developed. The
      smooth surface of IHP QD layers ensures ordered packing of the OSC molecules
      above them. The OSCs significantly improve the transportation of the photoexcited
      charges, and the gate effect of the transistor structure significantly enhances
      the photoresponsivity while simultaneously maintaining high Iphoto /Idark ratio.
      The devices exhibit outstanding optoelectronic properties in terms of
      photoresponsivity (1.7 * 104 A W-1 ), detectivity (2.0 * 1014 Jones), external
      quantum efficiency (67000%), Iphoto /Idark ratio (8.1 * 104 ), and stability (100
      d in air). The overall performances of our devices are superior to state-of-the
      art IHP photodetectors. The strategy utilized here is general and can be easily
      applied to many other perovskite photodetectors.

PMID- 29027732
TI  - Blunt cerebrovascular injury: early recognition and treatment options in
      asymptomatic patient.

PMID- 29027733
TI  - Improvement of wheat seed vitality by dielectric barrier discharge plasma
      treatment.
AB  - Influences of discharge voltage on wheat seed vitality were investigated in a
      dielectric barrier discharge (DBD) plasma system at atmospheric pressure and
      temperature. Six different treatments were designed, and their discharge voltages
      were 0.0, 9.0, 11.0, 13.0, 15.0, and 17.0 kV, respectively. Fifty seeds were
      exposed to the DBD plasma atmosphere with an air flow rate of 1.5 L min-1 for 4
      min in each treatment, and then the DBD plasma-treated seeds were prepared for
      germination in several Petri dishes. Each treatment was repeated three times.
      Germination indexes, growth indexes, surface topography, water uptake,
      permeability, and alpha-amylase activity were measured. DBD plasma treatment at
      appropriate energy levels had positive effects on wheat seed germination and
      seedling growth. The germination potential, germination index, and vigor index
      significantly increased by 31.4%, 13.9%, and 54.6% after DBD treatment at 11.0
      kV, respectively, in comparison to the control. Shoot length, root length, dry
      weight, and fresh weight also significantly increased after the DBD plasma
      treatment. The seed coat was softened and cracks were observed, systematization
      of the protein was strengthened, and amount of free starch grain increased after
      the DBD plasma treatment. Water uptake, relative electroconductivity, soluble
      protein, and alpha-amylase activity of the wheat seed were also significantly
      improved after the DBD plasma treatment. Roles of active species and ultraviolet
      radiation generated in the DBD plasma process in wheat seed germination and
      seedling growth are proposed. Bioelectromagnetics. 39:120-131, 2018. (c) 2017
      Wiley Periodicals, Inc.

PMID- 29027734
TI  - High resolution visualization and exo-proteomics reveal the physiological role of
      XlnR and AraR in plant biomass colonization and degradation by Aspergillus niger.
AB  - In A. niger, two transcription factors, AraR and XlnR, regulate the production of
      enzymes involved in degradation of arabinoxylan and catabolism of the released l
      arabinose and d-xylose. Deletion of both araR and xlnR in leads to reduced
      production of (hemi)cellulolytic enzymes and reduced growth on arabinan,
      arabinogalactan and xylan. In this study, we investigated the colonization and
      degradation of wheat bran by the A. niger reference strain CBS 137562 and
      araR/xlnR regulatory mutants using high-resolution microscopy and exo-proteomics.
      We discovered that wheat bran flakes have a 'rough' and 'smooth' surface with
      substantially different affinity towards fungal hyphae. While colonization of the
      rough side was possible for all strains, the xlnR mutants struggled to survive on
      the smooth side of the wheat bran particles after 20 and 40 h post inoculation.
      Impaired colonization ability of the smooth surface of wheat bran was linked to
      reduced potential of DeltaxlnR to secrete arabinoxylan and cellulose-degrading
      enzymes and indicates that XlnR is the major regulator that drives colonization
      of wheat bran in A. niger.

PMID- 29027735
TI  - Temporal trends in percutaneous coronary interventions thru the drug eluting
      stent era: Insights from 18,641 procedures performed over 12-year period.
AB  - BACKGROUND: The last decade, regarded as the DES era in PCI, has witnessed
      significant advances in the management of coronary disease. We aimed to assess
      temporal trends in the practice and outcome of percutaneous coronary intervention
      (PCI) during the drug eluting stent (DES) era. METHODS: We analyzed 18,641
      consecutive PCI's performed between January 2004 and December 2016, distinguished
      by procedural date (Q1 : 2004-2006, n = 4,865; Q2 : 2007-2009, n = 4,977; Q3 :
      2010-2012, n = 4,230; Q4 : 2013-2016, n = 4,569). RESULTS: At presentation, mean
      patients age was 65 (+/-11) years and 22.8% were females. Over time, there was a
      rise in the relative number of octogenarians (Q1 : 10.7% vs Q4 : 15.5%, P <
      0.001) and an increase in the burden of most comorbidities (e.g., left
      ventricular dysfunction >= moderate and chronic kidney disease, P < 0.001 for
      both). Despite a 2-fold increase in the rate of complex interventions, and a 3
      fold increase in the rate of unprotected left-main angioplasty (P < 0.001 for
      both), the radial approach was increasingly adopted (Q1 : 2% to Q4 : 63.5%, P <
      0.001). DES implantation increased from 43% to 83% at the expense of bare metal
      stent (BMS) application, and accompanied by drug coated balloon sprout to 1.8%, P
      < 0.001. Kaplan-Meier survival curves revealed a time-based enhanced outcome,
      with a decreased rate of death, MI, target vessel revascularization and CABG over
      the years. CONCLUSIONS: In the last decade, PCI has evolved to offer better
      outcome to more elderly, sicker patient population, with more complex coronary
      disease interventions. The shift to second generation DES and to enhanced PCI
      techniques may explain part of this progress.

PMID- 29027737
TI  - An optical coherence tomography study of neointimal morphology and strut coverage
      at different time intervals from implantation of biodegradable polymer-coated
      sirolimus-eluting stents.
AB  - OBJECTIVES: The aim of the study was to capture the evolution of neointima after
      implantation of a biodegradable polymer-coated, sirolimus-eluting, cobalt
      chromium coronary stent system (BP-DES). BACKGROUND: Optical coherence tomography
      (OCT) suggests that in-stent neointimal morphology influences clinical outcomes
      after DES implantation. METHODS: Sixty patients treated with single BP-DES
      implantation were examined by quantitative coronary angiography (QCA) and OCT at
      3, 6, and 12-month follow-up. RESULTS: Median late lumen loss by QCA (mm) was
      0.04 (IQR 0, 0.08), 0.17 (IQR 0, 0.32), and 0.14 (IQR 0.07, 0.31) at 3, 6, and 12
      month follow-up respectively (P = 0.03). OCT cross-section multilevel analysis
      showed uncovered struts in 3.90%, 1.78%, and 0.02% of struts respectively (P =
      0.03). The corresponding malapposition rates were 0.12%, 0.04%, and 0%. Lipid
      rich neointima was observed only at 12-month follow-up in one restenotic lesion
      (0.77% cross-sections) that was accountable for the only target vessel
      revascularization. The homogeneous pattern was prevalent at all three time
      points, but its incidence displayed an upward trend (3 months: 59%; 6 months:
      71%; 12 months: 88%) despite no difference in neointimal volume between 6 and 12
      months. Conversely, a trend could be observed of decreasing incidence of
      heterogeneous pattern as the follow-up length increased. CONCLUSIONS: In this
      study of a single-type BP-DES, the majority of stent struts were covered within 3
      months from implantation. While the quantitative neointimal accumulation
      plateaued at 6 months with no further significant increase beyond 6 months, the
      neointima continued to evolve qualitatively and mature along with better strut
      coverage between 6 and 12 months after implantation.

PMID- 29027736
TI  - Unravelling the Redox-catalytic Behavior of Ce4+ Metal-Organic Frameworks by X
      ray Absorption Spectroscopy.
AB  - The introduction of Ce4+ as a structural cation has been shown to be a promising
      route to redox active metal-organic frameworks (MOFs). However, the mechanism by
      which these MOFs act as redox catalysts remains unclear. Herein, we present a
      detailed study of the active site in [Ce6 O4 (OH)4 ]-based MOFs such as Ce-UiO
      66, involved in the aerobic oxidation of benzyl alcohol, chosen as a model redox
      reaction. X-ray absorption spectroscopy (XAS) data confirm the reduction of up to
      one Ce4+ ion per Ce6 cluster with a corresponding outwards radial shift due to
      the larger radius of the Ce3+ cation, while not compromising the structural
      integrity of the framework, as evidenced by powder X-ray diffraction. This
      unambiguously demonstrates the involvement of the metal node in the catalytic
      cycle and explains the need for 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) as a
      redox mediator to bridge the gap between the one-electron oxidation of the Ce4+
      /Ce3+ couple and the two-electron alcohol oxidation. Finally, an improved
      catalytic system with Ce-MOF-808 and TEMPO was developed which outperformed all
      other tested Ce4+ -MOFs.

PMID- 29027738
TI  - The development of the cucullaris muscle and the branchial musculature in the
      Longnose Gar, (Lepisosteus osseus, Lepisosteiformes, Actinopterygii) and its
      implications for the evolution and development of the head/trunk interface in
      vertebrates.
AB  - The vertebrate head/trunk interface is the region of the body where the different
      developmental programs of the head and trunk come in contact. Many anatomical
      structures that develop in this transition zone differ from similar structures in
      the head or the trunk. This is best exemplified by the cucullaris/trapezius
      muscle, spanning the head/trunk interface by connecting the head to the pectoral
      girdle. The source of this muscle has been claimed to be either the unsegmented
      head mesoderm or the somites of the trunk. However most recent data on the
      development of the cucullaris muscle are derived from tetrapods and information
      from actinopterygian taxa is scarce. We used classical histology in combination
      with fluorescent whole-mount antibody staining and micro-computed tomography to
      investigate the developmental pattern of the cucullaris and the branchial muscles
      in a basal actinopterygian, the Longnose gar (Lepisosteus osseus). Our results
      show (1) that the cucullaris has been misidentified in earlier studies on its
      development in Lepisosteus. (2) Cucullaris development is delayed compared to
      other head and trunk muscles. (3) This developmental pattern of the cucullaris is
      similar to that reported from some tetrapod taxa. (4) That the retractor dorsalis
      muscle of L. osseus shows a delayed developmental pattern similar to the
      cucullaris. Our data are in agreement with an explanatory scenario for the
      cucullaris development in tetrapods, suggesting that these mechanisms are
      conserved throughout the Osteichthyes. Furthermore the developmental pattern of
      the retractor dorsalis, also spanning the head/trunk interface, seems to be
      controlled by similar mechanisms.

PMID- 29027739
TI  - Erratum.

PMID- 29027740
TI  - Effective tolerance based on resource reallocation is a virus-specific defence in
      Arabidopsis thaliana.
AB  - Plant viruses often harm their hosts, which have developed mechanisms to prevent
      or minimize the effects of virus infection. Resistance and tolerance are the two
      main plant defences to pathogens. Although resistance to plant viruses has been
      studied extensively, tolerance has received much less attention. Theory predicts
      that tolerance to low-virulent parasites would be achieved through resource
      reallocation from growth to reproduction, whereas tolerance to high-virulent
      parasites would be attained through shortening of the pre-reproductive period. We
      have shown previously that the tolerance of Arabidopsis thaliana to Cucumber
      mosaic virus (CMV), a relatively low-virulent virus in this host, accords to
      these predictions. However, whether other viruses trigger the same response, and
      how A. thaliana copes with highly virulent virus infections remains unexplored.
      To address these questions, we challenged six A. thaliana wild genotypes with
      five viruses with different genomic structures, life histories and transmission
      modes. In these plants, we quantified virus multiplication, virulence, and the
      effects of infection on plant growth and reproduction, and on the developmental
      schedule. Our results indicate that virus multiplication varies according to the
      virus * host genotype interaction. Conversely, effective tolerance is observed
      only on CMV infection, and is associated with resource reallocation from growth
      to reproduction. Tolerance to the other viruses is observed only in specific host
      virus combinations and, at odds with theoretical predictions, is linked to longer
      pre-reproductive periods. These findings only partially agree with theoretical
      predictions, and contribute to a better understanding of pathogenic processes in
      plant-virus interactions.

PMID- 29027741
TI  - Recommendations for standardized risk factor definitions in pediatric hospital
      acquired venous thromboembolism to inform future prevention trials: communication
      from the SSC of the ISTH.

PMID- 29027742
TI  - Disentangling causation: complex roles of coral-associated microorganisms in
      disease.
AB  - Rapidly changing climate regimes combined with other anthropogenic pressures are
      implicated in increased disease epizootics among reef building corals, resulting
      in changing habitat structure. These accumulated stressors directly contribute to
      disease outbreaks by compromising the coral host immune system, modulating
      virulence of microbial pathogens and/or disrupting the balance within the
      microbiome of the holobiont. Disentangling coral disease causation has been
      challenging, and while progress has been made for certain diseases in terms of
      the roles the associated microorganisms play, it is evident that like in other
      marine or terrestrial systems, compromised host health cannot always be
      attributed to a single causative agent. Here, we summarize the current state in
      knowledge of microbial induced coral diseases, and discuss challenges and
      strategies to further disentangle disease causation. With the major environmental
      pressures coral reefs face over the next century, understanding interactions
      between host, environmental and microbial causative agent(s) that lead to
      disease, is still a priority to enable development of effective strategies for
      building resilience into coral populations.

PMID- 29027743
TI  - Generalized pustular psoriasis triggered by Zika virus infection.
AB  - Zika virus is an emerging arbovirus, which is expanding in epidemic proportions
      through tropical and subtropical areas of the world. Although Zika is linked to a
      number of congenital and neurological complications, there is scarce knowledge on
      the impact of ZIKV infection in human skin. We report the case of a 68-year old
      woman who presented with generalized pustular psoriasis after a preceding and
      otherwise uneventful episode of ZIKV infection. Based on recent experimental data
      on the biology of ZIKV infection in the cutaneous environment, we speculate that
      ZIKV may have directly triggered the development of generalized pustular
      psoriasis by stimulation of keratinocyte-derived mediators of inflammation and a
      polyfunctional T-cell driven immune reaction in the cutaneous milieu.

PMID- 29027745
TI  - The importance of measuring skin resistance for electrical nociceptive
      stimulation in standing horses.

PMID- 29027746
TI  - Racehorse injuries: Have we only got half the story?

PMID- 29027744
TI  - Concise Review: Induced Pluripotent Stem Cell Models for Neuropsychiatric
      Diseases.
AB  - The major neuropsychiatric conditions of schizophrenia, affective disorders, and
      infantile autism are characterized by chronic symptoms of episodic, stable, or
      progressive nature that result in significant morbidity. Symptomatic treatments
      are the mainstay but do not resolve the underlying disease processes, which are
      themselves poorly understood. The prototype psychotropic drugs are of variable
      efficacy, with therapeutic mechanisms of action that are still uncertain. Thus,
      neuropsychiatric disorders are ripe for new technologies and approaches with the
      potential to revolutionize mechanistic understanding and drive the development of
      novel targeted treatments. The advent of methods to produce patient-derived stem
      cell models and three-dimensional organoids with the capacity to differentiate
      into neurons and the various neuronal cellular lineages mark such an advance. We
      discuss numerous techniques involved, their applications, and areas that require
      further optimization. Stem Cells Translational Medicine 2017;6:2062-2070.

PMID- 29027747
TI  - Isn't it high time we talked openly about racism?

PMID- 29027748
TI  - Microfluidics approach to investigate the role of dynamic similitude in osteocyte
      mechanobiology.
AB  - Fluid flow is an important regulator of cell function and metabolism in many
      tissues. Fluid shear stresses have been used to level the mechanical stimuli
      applied in vitro with what occurs in vivo. However, these experiments often lack
      dynamic similarity, which is necessary to ensure the validity of the model. For
      interstitial fluid flow, the major requirement for dynamic similarity is the
      Reynolds number (Re), the ratio of inertial to viscous forces, is the same
      between the system and model. To study the necessity of dynamic similarity for
      cell mechanotransduction studies, we investigated the response of osteocyte-like
      MLO-Y4 cells to different Re flows at the same level of fluid shear stress.
      Osteocytes were chosen for this study as flows applied in vitro and in vivo have
      Re that are orders of magnitude different. We hypothesize that osteocytes'
      response to fluid flow is Re dependent. We observed that cells exposed to lower
      and higher Re flows developed rounded and triangular morphologies, respectively.
      Lower Re flows also reduced apoptosis rates compared to higher Re flows.
      Furthermore, MLO-Y4 cells exposed to higher Re flows had stronger calcium
      responses compared to lower Re flows. However, by also controlling for flow rate,
      the lower Re flows induced a stronger calcium response; while degradation of
      components of the osteocyte glycocalyx reversed this effect. This work suggests
      that osteocytes are highly sensitive to differences in Re, independent of just
      shear stresses, supporting the need for improved in vitro flow platforms that
      better recapitulate the physiological environment. (c) 2017 Orthopaedic Research
      Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:663-671, 2018.

PMID- 29027749
TI  - Permanent tooth agenesis in individuals with non-syndromic Robin sequence: a
      systematic review and meta-analysis.
AB  - OBJECTIVES: To evaluate prevalence rates and patterns of permanent tooth agenesis
      in individuals with non-syndromic Robin sequence (ns-RS). MATERIAL AND METHODS:
      Two investigators independently carried out a literature search, using PubMed,
      Web of Science, Ovid, EMBASE and the Cochrane Library, identifying articles
      relating to permanent tooth agenesis, diagnosed using panoramic radiographs, in
      individuals with ns-RS. The outcomes desired were prevalence rates and patterns
      of permanent tooth agenesis. The final search was carried out in January 2017.
      RESULTS: Six articles were selected for inclusion, with a total of 448
      individuals with ns-RS. Data available in each study varied which allowed
      conducting further specific meta-analyses only on sample sizes of 339 or 378
      individuals from three or four of the six included articles. The overall
      estimated prevalence rate of permanent tooth agenesis was 42% (95% CI: 35%-48%),
      excluding third molars, with no sex predilection. In individuals with tooth
      agenesis, approximately 30% had one missing tooth while 40% had two missing
      teeth. Tooth agenesis was more commonly bilateral (Relative Risk 2) and found in
      the mandible (Relative Risk 1.6). The highest prevalence of permanent tooth
      agenesis was found for mandibular second premolars (26%) followed by maxillary
      second premolars (14%). The most common tooth agenesis patterns were the agenesis
      of both mandibular second premolars, followed by the agenesis of all second
      premolars. CONCLUSION: Individuals with ns-RS have high prevalence rates of
      permanent tooth agenesis. The most prevalent tooth agenesis patterns are
      bilateral symmetric tooth agenesis, most commonly agenesis of both mandibular
      second premolars.

PMID- 29027750
TI  - A Simple and Robust Method for Culturing Human-Induced Pluripotent Stem Cells in
      an Undifferentiated State Using Botulinum Hemagglutinin.
AB  - Clinical and industrial applications of human-induced pluripotent stem cells
      (hiPSCs) is hindered by the lack of robust culture strategies capable of
      sustaining a culture in an undifferentiated state. Here, a simple and robust
      hiPSC-culture-propagation strategy incorporating botulinum hemagglutinin (HA)
      mediated selective removal of cells deviating from an undifferentiated state is
      developed. After HA treatment, cell-cell adhesion is disrupted, and deviated
      cells detached from the central region of the colony to subsequently form tight
      monolayer colonies following prolonged incubation. The authors find that the
      temporal and dose-dependent activity of HA regulated deviated-cell removal and
      recoverability after disruption of cell-cell adhesion in hiPSC colonies. The
      effects of HA are confirmed under all culture conditions examined, regardless of
      hiPSC line and feeder-dependent or -free culture conditions. After routine
      application of our HA-treatment paradigm for serial passages, hiPSCs maintains
      expression of pluripotent markers and readily forms embryoid bodies expressing
      markers for all three germ-cell layers. This method enables highly efficient
      culturing of hiPSCs and use of entire undifferentiated portions without having to
      pick deviated cells manually. This simple and readily reproducible culture
      strategy is a potentially useful tool for improving the robust and scalable
      maintenance of undifferentiated hiPSC cultures.

PMID- 29027751
TI  - The emerging role of mRNA methylation in normal and pathological behavior.
AB  - Covalent RNA modifications were recently rediscovered as abundant RNA chemical
      tags. Similarly to DNA epigenetic modifications, they have been proposed as
      essential regulators of gene expression. Here we focus on 3 of the most abundant
      adenosine methylations: N6-methyladenosine (m6 A), N6,2'-O-dimethyladenosine (m6
      Am) and N1-methyladenosine (m1 A). We review the potential role of these
      modifications on mature mRNA in regulating gene expression within the adult
      brain, nervous system function and normal and pathological behavior. Dynamic mRNA
      modifications, summarized as the epitranscriptome, regulate transcript
      maturation, translation and decay, and thus crucially determine gene expression
      beyond primary transcription regulation. However, the extent of this regulation
      in the healthy and maladapted adult brain is poorly understood. Analyzing this
      novel layer of gene expression control in addition to epigenetics and
      posttranslational regulation of proteins will be highly relevant for
      understanding the molecular underpinnings of behavior and psychiatric disorders.

PMID- 29027752
TI  - Label-Free Multiplex DNA Detection Utilizing Projected Capacitive Touchscreen.
AB  - A novel strategy to achieve label-free multiplex DNA detection system based on
      the projected capacitive touchscreen is developed. Touchscreen panel is first
      fabricated by patterning the ITO (indium-tin-oxide) electrode array on the glass
      wafer, and the electrodes are modified with the respective capture probe DNA
      sequences complementary to hemagglutinin1 (H1), neuraminidase1 (N1), and matrix1
      (M1) DNA to demonstrate the molecular diagnosis of H1N1 influenza virus as a
      model pathogen. DNA sample is applied to the electrodes to allow hybridization of
      target DNA with the corresponding complementary capture probe. As a result, the
      hybridization event significantly enhanced the capacitance on the electrode,
      which can be very conveniently detected by the projected capacitive touchscreen.
      Based on this design principle, the authors have successfully detected target
      regions of H1N1 influenza virus in a label-free multiplexed manner. This
      touchscreen-based detecting system would greatly benefit the point-of-care
      testing (POCT) in various diagnostic applications.

PMID- 29027753
TI  - Li+ Ion Conductors with Adamantane-Type Nitridophosphate Anions beta-Li10 P4 N10
      and Li13 P4 N10 X3 with X=Cl, Br.
AB  - beta-Li10 P4 N10 and Li13 P4 N10 X3 with X=Cl, Br have been synthesized from
      mixtures of P3 N5 , Li3 N, LiX, LiPN2 , and Li7 PN4 at temperatures below 850 
      degrees C. beta-Li10 P4 N10 is the low-temperature polymorph of alpha-Li10 P4 N10
      and crystallizes in the trigonal space group R3. It is made up of non-condensed
      [P4 N10 ]10- T2 supertetrahedra, which are arranged in sphalerite-analogous
      packing. Li13 P4 N10 X3 (X=Cl, Br) crystallizes in the cubic space group Fm3?m .
      Both isomorphic compounds comprise adamantane-type [P4 N10 ]10- , Li+ ions, and
      halides, which form octahedra. These octahedra build up a face-centered cubic
      packing, whose tetrahedral voids are occupied by the [P4 N10 ]10- ions. The
      crystal structures have been elucidated from X-ray powder diffraction data and
      corroborated by EDX measurements, solid-state NMR, and FTIR spectroscopy.
      Furthermore, we have examined the phase transition between alpha- and beta-Li10
      P4 N10 . To confirm the ionic character, the migration pathways of the Li+ ions
      have been evaluated and the ion conductivity and its temperature dependence have
      been determined by impedance spectroscopy. XPS measurements have been carried out
      to analyze the stability with respect to Li metal.

PMID- 29027755
TI  - Compressed sensing approach for wrist vein biometrics.
AB  - The work describes features of the compressed sensing (CS) approach utilized for
      development of a wearable system for wrist vein recognition with single-pixel
      detection; we consider this system useful for biometrics authentication purposes.
      The CS approach implies use of a spatial light modulation (SLM) which, in our
      case, can be performed differently-with a liquid crystal display or diffusely
      scattering medium. We show that compressed sensing combined with above-mentioned
      means of SLM allows us to avoid using an optical system-a limiting factor for
      wearable devices. The trade-off between the 2 different SLM approaches regarding
      issues of practical implementation of CS approach for wrist vein recognition
      purposes is discussed. A possible solution of a misalignment problem-a typical
      issue for imaging systems based upon 2D arrays of photodiodes-is also proposed.
      Proposed design of the wearable device for wrist vein recognition is based upon
      single-pixel detection.

PMID- 29027754
TI  - Afatinib treatment of a squamous lung cancer after tumor progression of
      nivolumab.
AB  - Nivolumab prolonged disease control in a patient with advanced squamous lung
      cancer that was refractory to multiple treatments. The rapid eradication of
      cancer after the administration of nivolumab caused hemoptysis and repeated
      infection. Six months after immunotherapy, mediastinal lymph node metastasis
      developed and afatinib effectively relieved dysphonia associated with nerve
      paralysis.

PMID- 29027756
TI  - What is the outcome in patients with acute leukaemia who survive severe acute
      graft-versus-host disease?
AB  - BACKGROUND: Acute graft-versus-host disease (aGVHD) is a major complication of
      allogeneic haematopoietic stem cell transplantation (HSCT). With new promising
      therapies, survival may improve for severe aGVHD. OBJECTIVES: We wanted to
      analyze the long-term outcome in patients who survive severe aGVHD. METHODS: This
      study was a landmark analysis of 23 567 patients with acute Leukaemia who
      survived for more than 6 months after HSCT, 2002-2014. Patients alive after
      severe aGVHD (n = 1738) were compared to controls. RESULTS: Patients with severe
      aGVHD had higher non-relapse mortality (NRM) and higher rate of extensive chronic
      GVHD (cGVHD) than the controls (P < 10-5 ). The probability of relapse was
      significantly lower in the severe aGVHD group, but Leukaemia-free survival (LFS)
      and overall survival were significantly lower than for the controls (P < 10-5 ).
      Five-year LFS in patients with severe aGVHD was 49%, as opposed to 61% in
      controls with no or mild GVHD and 59% in patients with moderate GVHD.
      CONCLUSIONS: HSCT patients who survive severe aGVHD have higher risk of
      developing extensive cGVHD, a higher NRM, a lower relapse probability, and lower
      LFS than other HSCT patients. This study is a platform for outcome analysis in
      patients treated with novel therapies for acute GVHD.

PMID- 29027757
TI  - Straightforward Design of Fluorescent Receptors for Sulfate: Study of Non
      Covalent Interactions Contributing to Host-Guest Formation.
AB  - A straightforward design of receptors for binding and sensing of sulfate in
      aqueous medium was developed. The design involves the connection of two
      naphthalimide-based pH probes through a hydrogen-bonding motif. The structure of
      the receptor-sulfate complex, predicted by DFT calculations, was unambiguously
      confirmed by NMR measurements. There are three major interactions stabilizing the
      host-guest complex: electrostatic interactions, hydrogen bonding, and stacking
      interactions of the dyes. Study of two control receptors containing either one
      dye or methyl amide groups instead of amides, revealed that electrostatic and
      hydrogen bonding interactions contribute the most to affinity and selectivity of
      receptors. The receptors can detect sulfate in a 1:1 THF-buffer mixture in pH
      window 3.6-4.5 demonstrating up to 7-fold fluorescence enhancement. To the best
      of our knowledge, the reported PET (photoinduced electron transfer) anion probes
      possess the largest response for sulfate in aqueous solution yet described.

PMID- 29027758
TI  - Characterization of UDP-glucuronosyltransferase genes and their possible roles in
      multi-insecticide resistance in Plutella xylostella (L.).
AB  - BACKGROUND: Uridine diphosphate-glucuronosyltransferases (UGTs), as
      multifunctional detoxification enzymes, play important roles in the
      biotransformation of various compounds. However, their roles in insecticide
      resistance are still unclear. This study presents a genome-wide identification of
      the UGTs in diamondback moth, Plutella xylostella (L.), a notorious insect pest
      of cruciferous crops worldwide. The possible roles of these UGTs in insecticide
      resistance were evaluated. RESULTS: A total of 21 putative UGTs in P. xylostella
      were identified. Quantitative real-time polymerase chain reaction (PCR)-based
      analyses showed that all the UGT genes were expressed in all tested developmental
      stages and tissues. Bioassay results indicated that a field-collected population
      (BL) was resistant to 9 of 10 commonly used insecticides, and 10 of 21 UGT mRNAs
      were upregulated in the BL population. Exposure to the LC50 of each insecticide
      affected the expression of most UGT genes. Among these, the expression levels of
      UGT40V1, UGT45B1 and UGT33AA4 were induced by more than five insecticides,
      whereas indoxacarb and metaflumizone significantly repressed the expression of
      most UGT genes. CONCLUSION: UGTs may play important roles in the metabolism of
      commonly used insecticides in P. xylostella. These findings provide valuable
      information for further research on the physiological and toxicological functions
      of specific UGT genes in P. xylostella. (c) 2017 Society of Chemical Industry.

PMID- 29027759
TI  - Greek Physiotherapists' Perspectives on Rehabilitation Following Total Knee
      Replacement: a Descriptive Survey.
AB  - BACKGROUND AND PURPOSE: In Greece, as in many countries, there is a scarcity of
      evidence in the type of physiotherapy services offered for the rehabilitation of
      total knee replacement (TKR). Despite the number of TKRs annually performed in
      Greece (over 10,000), there are no available clinical guidelines as to the
      content of best physiotherapy practice. The aim of this nationwide survey
      undertaken by physiotherapists treating TKR patients post-operatively was to
      record standard practice and services available in Greece. METHODS: Design: cross
      country survey Ten per cent of all registered physiotherapists working in
      public/private sectors were recruited. The developed survey comprised of
      questions regarding therapists' profile, protocols implemented at different
      stages of rehabilitation and the aims and modalities used. RESULTS: A 58.7%
      response rate was achieved, where 36% (47/132) of respondents were treating
      patients in the inpatient phase and 64% (85/132) after hospital discharge.
      Patients in Greece are discharged with a home-based exercise program (56.7%) and,
      to a lesser extent, are referred to rehabilitation centres (13.3%).
      Strengthening, range of movement and functionality seemed to be the primary goals
      especially in the inpatient phase, whereas in the outpatient phase, apart from
      the larger differences identified, functionality and balance training were more
      frequently reported. CONCLUSIONS: No significant variations in practice were
      found during inpatient rehabilitation, whilst there seemed to be diversity across
      outpatient physiotherapy programs. The current survey suggests that patient's
      general health and psychological and behavioural issues are the criteria by which
      physiotherapists select the volume of implemented exercise and progression.
      However, no specific guidelines were followed. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 29027761
TI  - Oxidative stress and mitochondrial dynamics malfunction are linked in Pelizaeus
      Merzbacher disease.
AB  - Pelizaeus-Merzbacher disease (PMD) is a fatal hypomyelinating disorder
      characterized by early impairment of motor development, nystagmus,
      choreoathetotic movements, ataxia and progressive spasticity. PMD is caused by
      variations in the proteolipid protein gene PLP1, which encodes the two major
      myelin proteins of the central nervous system, PLP and its spliced isoform DM20,
      in oligodendrocytes. Large duplications including the entire PLP1 gene are the
      most frequent causative mutation leading to the classical form of PMD. The Plp1
      overexpressing mouse model (PLP-tg66/66 ) develops a phenotype very similar to
      human PMD, with early and severe motor dysfunction and a dramatic decrease in
      lifespan. The sequence of cellular events that cause neurodegeneration and
      ultimately death is poorly understood. In this work, we analyzed patient-derived
      fibroblasts and spinal cords of the PLP-tg66/66 mouse model, and identified redox
      imbalance, with altered antioxidant defense and oxidative damage to several
      enzymes involved in ATP production, such as glycolytic enzymes, creatine kinase
      and mitochondrial proteins from the Krebs cycle and oxidative phosphorylation. We
      also evidenced malfunction of the mitochondria compartment with increased ROS
      production and depolarization in PMD patient's fibroblasts, which was prevented
      by the antioxidant N-acetyl-cysteine. Finally, we uncovered an impairment of
      mitochondrial dynamics in patient's fibroblasts which may help explain the
      ultrastructural abnormalities of mitochondria morphology detected in spinal cords
      from PLP-tg66/66 mice. Altogether, these results underscore the link between
      redox and metabolic homeostasis in myelin diseases, provide insight into the
      pathophysiology of PMD, and may bear implications for tailored pharmacological
      intervention.

PMID- 29027763
TI  - Primary Sjogren's syndrome in Asia: Yin and Yang?

PMID- 29027762
TI  - Fresh Noncultured Endothelial Progenitor Cells Improve Neonatal Lung Hyperoxia
      Induced Alveolar Injury.
AB  - Treatment of preterm human infants with high oxygen can result in disrupted lung
      alveolar and vascular development. Local or systemic administration of
      endothelial progenitor cells (EPCs) is reported to remedy such disruption in
      animal models. In this study, the effects of both fresh (enriched for KDR) and
      cultured bone marrow (BM)-derived cell populations with EPC characteristics were
      examined following hyperoxia in neonatal mouse lungs. Intraperitoneal injection
      of fresh EPCs into five-day-old mice treated with 90% oxygen resulted in full
      recovery of hyperoxia-induced alveolar disruption by 56 days of age. Partial
      recovery in septal number following hyperoxia was observed following injection of
      short-term cultured EPCs, yet aberrant tissue growths appeared following
      injection of long-term cultured cells. Fresh and long-term cultured cells had no
      impact on blood vessel development. Short-term cultured cells increased blood
      vessel number in normoxic and hyperoxic mice by 28 days but had no impact on day
      56. Injection of fresh EPCs into normoxic mice significantly reduced
      alveolarization compared with phosphate buffered saline-injected normoxic
      controls. These results indicate that fresh BM EPCs have a higher and safer
      corrective profile in a hyperoxia-induced lung injury model compared with
      cultured BM EPCs but may be detrimental to the normoxic lung. The appearance of
      aberrant tissue growths and other side effects following injection of cultured
      EPCs warrants further investigation. Stem Cells Translational Medicine
      2017;6:2094-2105.

PMID- 29027764
TI  - A Decatwistacene with an Overall 170 degrees  Torsion.
AB  - Two different lengths of twistacenes, namely hexatwistacene and decatwistacene,
      induced by steric hindrance between imide groups and neighboring annulated
      benzene rings, were synthesized by bottom-up synthesis of palladium-catalyzed
      Suzuki cross-coupling and C-H activation. Single-crystal X-ray analyses revealed
      that decatwistacene, which is the longest twistacene reported, exhibits an
      astonishing overall end-to-end torsion angle of about 170 degrees , the largest
      torsion angle reported. Both twistacenes have an enhanced solubility and
      stability with respect to light and oxygen owing to their large twisting
      deformations together with much lower LUMO levels caused by the introduction of
      imide groups, opening a window to the narrowest chiral graphene nanoribbons with
      good stability and processability.

PMID- 29027765
TI  - Factor XIII deficiency diagnosis: Challenges and tools.
AB  - Factor XIII deficiency (FXIIID) is a rare hereditary bleeding disorder arising
      from heterogeneous mutations, which can lead to life-threatening hemorrhage. The
      diagnosis of FXIIID is challenging due to normal standard coagulation assays
      requiring specific FXIII assays for diagnosis, which is especially difficult in
      developing countries. This report presents an overview of FXIIID diagnosis and
      laboratory methods and suggests an algorithm to improve diagnostic efficiency and
      prevent missed or delayed FXIIID diagnosis. Assays measuring FXIII activity: The
      currently available assays utilized to diagnose FXIIID, including an overview of
      their complexity, reliability, sensitivity, and specificity, as well as
      mutational analysis are reviewed. The use of a FXIII inhibitor assay is
      described. Diagnostic tools in FXIIID: Many laboratories are not equipped with
      quantitative FXIII activity assays, and if available, limitations in lower
      activity ranges are important to consider. Clot solubility tests are not
      standardized, have a low sensitivity, and are therefore not recommended as
      routine screening test; however, they are the first screening test in almost all
      coagulation laboratories in developing countries. To minimize the number of
      patients with undiagnosed FXIIID, test quality should be improved in less well
      equipped laboratories. Common country-specific mutations may facilitate diagnosis
      through targeted genetic analysis in reference laboratories in suspected cases.
      However, genetic analysis may not be feasible in every country and may miss
      spontaneous mutations. Centralized FXIII activity measurements should also be
      considered. An algorithm for diagnosis of FXIIID including different approaches
      dependent upon laboratory capability is proposed.

PMID- 29027766
TI  - Kinetic Modeling of Mammalian Cell Culture Bioprocessing: The Quest to Advance
      Biomanufacturing.
AB  - Kinetic modeling is the most suitable framework to describe the dynamic behavior
      of mammalian cell culture although its industrial application is still in its
      infancy. Herein, the authors reviewed mammalian bioprocess relevant kinetic
      models, and found that the simple unstructured-unsegregated approach utilizing
      empirical Monod-type kinetics based on limiting substrates and inhibitory
      metabolites is commonly used due to its traceability and simple formalism.
      Notably, the available kinetic models are typically small to moderate in size,
      and the development of large-scale models is severely hampered by the scarcity of
      kinetic data and limitations in current parameter estimation methods. The recent
      availability of abundant high-throughput multi-omics datasets from mammalian cell
      cultures have now paved the way to improve parameterization of kinetic models,
      and integrate regulatory, signaling, and product quality related intracellular
      events, as well as cellular metabolism within the modeling framework. Ultimately,
      the authors foresee that multi-scale modeling is the way forward in building
      predictive kinetic models of mammalian cell culture to advance biomanufacturing.

PMID- 29027767
TI  - Monitoring of brown stink bug (Hemiptera: Pentatomidae) population dynamics in
      corn to predict its abundance using weather data.
AB  - The brown stink bug (BSB), Euschistus servus (Say) (Hemiptera: Pentatomidae), is
      a serious economic pest of corn production in the southeastern United States. The
      BSB population dynamics was monitored for 17 weeks from tasseling to preharvest
      of corn plants (i.e., late May to mid-September) using pheromone traps in three
      corn fields from 2005 to 2009. The trap data showed two peaks in early June and
      mid-August, respectively. The relationship between trap catch and pregrowing
      season weather data was examined using correlation and stepwise multiple factor
      regression analyses. Weather indices used for the analyses were accumulated
      growing degree day (AGDD), number of days with minimum temperature below 0 
      degrees C (Subz), accumulated daily maximum (AMaxT) and minimum temperatures
      (AMinT) and rainfall (ARain). The weather indices were calculated with lower (10 
      degrees C) and upper (35  degrees C) as biological thresholds. The parameters
      used in regression analysis were seasonal abundance (or overall mean of BSB adult
      catch) (BSBm), number of BSB adults caught at a peak (PeakBSB), and peak week
      (Peakwk). The BSBm was negatively related to high temperature (AmaxT or AGDD)
      consistently, whereas 1stPeakBSB was positively correlated to both ARain and
      Subz, irrespective of weather data durations (the first 4, 4.5, and 5 months). In
      contrast, the 7-month weather data (AGDD7) were negatively correlated to the BSBm
      only, but not correlated to the second PeakBSB. The 5-year monitoring study
      demonstrated that weather data can be used to predict the BSB abundance at its
      first peak in tasseling corn fields in the southeastern U.S. states.

PMID- 29027768
TI  - Religious Exemptions and Accommodations for Coverage of Certain Preventive
      Services Under the Affordable Care Act. Interim final rules with requestfor
      comments.
AB  - The United States has a long history of providing conscience protections in the
      regulation of health care for entities and individuals with objections based on
      religious beliefs and moral convictions. These interim final rules expand
      exemptions to protect religious beliefs for certain entities and individuals
      whose health plans are subject to a mandate of contraceptive coverage through
      guidance issued pursuant to the Patient Protection and Affordable Care Act. These
      rules do not alter the discretion of the Health Resources and Services
      Administration (HRSA), a component of the United States Department of Health and
      Human Services (HHS), to maintain the guidelines requiring contraceptive coverage
      where no regulatorily recognized objection exists. These rules also leave the
      "accommodation" process in place as an optional process for certain exempt
      entities that wish to use it voluntarily. These rules do not alter multiple other
      Federal programs that provide free or subsidized contraceptives for women at risk
      of unintended pregnancy.

PMID- 29027769
TI  - Moral Exemptions and Accommodations for Coverage of Certain Preventive Services
      Under the Affordable Care Act. Interim final rules with requestfor comments.
AB  - The United States has a long history of providing conscience protections in the
      regulation of health care for entities and individuals with objections based on
      religious beliefs or moral convictions. These interim final rules expand
      exemptions to protect moral convictions for certain entities and individuals
      whose health plans are subject to a mandate of contraceptive coverage through
      guidance issued pursuant to the Patient Protection and Affordable Care Act. These
      rules do not alter the discretion of the Health Resources and Services
      Administration, a component of the United States Department of Health and Human
      Services, to maintain the guidelines requiring contraceptive coverage where no
      regulatorily recognized objection exists. These rules also provide certain
      morally objecting entities access to the voluntary "accommodation" process
      regarding such coverage. These rules do not alter multiple other Federal programs
      that provide free or subsidized contraceptives for women at risk of unintended
      pregnancy.

PMID- 29027771
TI  - Two different placement paths in popliteal fossa with a novel nerve block needle
      for postoperative analgesia after foot and ankle surgery.
AB  - BACKGROUND: Previous studies have documented that single injection nearby the
      sciatic nerve bifurcation would influence the anesthesia and analgesia effect.
      But this is uncertain for preoperative continuous popliteal sciatic nerve block.
      This trial was conducted to compare two paths (proximal to the bifurcation and at
      the bifurcation) of ultrasound-guided continuous popliteal sciatic nerve block in
      foot and ankle surgery. METHODS: Forty recruited objects were randomly assigned
      to receive ultrasound-guided continuous popliteal sciatic nerve block at the
      puncture path proximal to the nerve bifurcation either at the nerve bifurcation.
      Subjects received an injection using a novel nerve block needle with external
      indwelling cannula guided by ultrasound invented by the corresponding author. The
      external indwelling cannula was inserted for postoperative analgesia. The primary
      outcome was NRS scores (at rest and during movement) times at 24 hours after
      surgery. The secondary outcomes included the measurements related to the
      performance of the nerve block and efficacy of analgesia, such as anesthesia
      effect grade, grade of nausea and vomiting, case number of patients with cannula
      leaking, occlusion or slipping, patient satisfaction, etc. RESULTS: During the
      surgery, six subjects in the proximal group needed additional analgesic,
      significantly different from one in the at bifurcation group (P<0.05). There was
      significant difference on anesthesia effect rating, 1.6+/-0.8 in the proximal
      group and 1.1+/-0.4 in another (P<0.05). The proximal group got 2.1+/-1.6 of NRS
      on rest at 24 hours and 1.7+/-1.5 at 48 hours, and the at bifurcation group got
      0.9+/-1.4 at 24 hours and 0.7+/-1.1 at 48 hours (P<0.05). The proximal group got
      more PCA times during 6-24 hours and 24-48 hours and lower satisfaction scores.
      CONCLUSIONS: Continuous popliteal sciatic nerve block at nerve bifurcation could
      receive better analgesia effect and more patients' satisfaction, rather than
      proximal to the bifurcation.

PMID- 29027770
TI  - Bispectral Index and non-Bispectral Index anesthetic protocols on postoperative
      recovery outcomes.
AB  - INTRODUCTION: The study aimed to compare Bispectral Index (BIS) and non-BIS
      anesthetic protocols on postoperative recovery outcomes. EVIDENCE ACQUISITION:
      Medline, PubMed, Cochrane, EMBASE, and Google Scholar databases were searched
      until January 21, 2016. EVIDENCE SYNTHESIS: Twenty-six studies were included with
      a total of 9537 patients. BIS monitoring was significantly associated with
      shorter time to eye opening (P=0.001), time to extubation (P<0.001), and time to
      orientation (P=0.002) compared with non-BIS monitoring. No difference between
      groups was seen with respect to hypoxemia, postoperative nausea and vomiting
      (PONV), time to oral fluid intake, and length of Postanesthesia Care Unit (PACU)
      stay (P values >=0.185). CONCLUSIONS: The use of BIS-monitoring is superior to
      non-BIS monitored anesthesia in terms of shorter time to eye-opening, extubation,
      and orientation. BIS monitor may be considered a safe and effective method for
      monitoring depth of anesthesia during surgery.

PMID- 29027772
TI  - Supraglottic airway devices: indications, contraindications and management.
AB  - Supraglottic airway devices (SADs) have become an essential tool in airway
      management. Over the past three decades, these devices have been increasingly
      adopted as an alternative to face mask ventilation and/or endotracheal
      intubation. The range of proposed uses and features has increased significantly.
      They are used in pre- and in-hospital settings, elective and emergency
      anesthesia, in spontaneously breathing and ventilated patients, as conduits for
      intubation, as a bridge to extubation and for airway rescue. With SADs, serious
      complications such as aspiration and loss of airway are rare and largely
      preventable. Adequate operator experience, familiarity with the selected device,
      attention to details and careful patient selection are fundamental to safety and
      proficiency. In this review, we explore the increasing proposed uses for SADs and
      discuss possible complications and the management of these.

PMID- 29027773
TI  - Perioperative pain management in cardiac surgery: a systematic review.
AB  - BACKGROUND: Every year, more than 1.5 million patients, who undergo cardiac
      surgery worldwide, are exposed to a series of factors that can trigger acute
      postoperative pain associated with hemodynamic instability, respiratory
      complications, and psychological disorders. Through an evaluation of literature
      data about postoperative pain in cardiac surgery we define unmet needs and
      potential objectives for future research on this often-underestimated problem.
      METHODS: Following PRISMA Guidelines, a systematic literature search was carried
      out by two independent researchers on Scopus, CINAHL, the Cochrane Library, and
      PubMed using the key words: (perioperative OR postoperative) analgesia AND
      "cardiac surgery." Papers concerning children, or published prior to 2000, were
      considered ineligible, as well as abstracts, animal studies, and studies written
      in languages other than English. RESULTS: Fifty-four papers were selected and
      subsequently divided into two main categories: systemic analgesic drugs and
      regional anesthesia techniques. CONCLUSIONS: Over the past 17 years, opioids are
      still the most extensively used therapy, whereas we found only few trials
      investigating other drugs (e.g. paracetamol). Regional anesthesia techniques,
      especially thoracic epidural analgesia and intrathecal morphine administration,
      can effectively treat pain, but have not yet showed any significant impact on
      major clinical outcomes, with several concerns related to their potential
      complications. To date multimodal analgesia with implementation of regional
      analgesia seems to be the best choice. In the future, better-designed studies
      should consider other drugs stratifying groups according to comorbidities and
      risk factors, as well as using standardized units of measurement.

PMID- 29027774
TI  - Rational approach to transfusion in liver transplantation.
AB  - For over 50 years patients with liver cirrhosis were considered to be at markedly
      increased risk of bleeding. This dogma was seemingly supported by abnormalities
      in standard laboratory tests (SLTs), such as the prothrombin time, that were
      interpreted as indicating a bleeding diathesis. However, publications from the
      last decade have revealed SLTs to be poor predictors of bleeding and it is now
      understood that stable patients with cirrhosis have a rebalanced haemostatic
      system and preserved thrombin generation. Viscoelastic tests (VETs), such as
      ROTEM(r) or TEGTM allow dynamic assessment of the entire coagulation process and
      provide a better illustration of the interactions between pro- and anticoagulants
      as well as platelets. Despite their documented success in reducing transfusion
      rates in liver transplantation more than 30 years ago, the adoption of VETs has
      been met with some resistance and has only recently gained significant momentum.
      Bleeding risk should be assessed in every patient undergoing invasive
      intervention and must consider markers of disease severity, underlying
      coagulation incompetence, anaemia and surgical factors. The recognition that
      bleeding in this patient cohort is predominantly linked to mechanistic factors
      such as portal hypertension, rather than primary coagulopathy, has led to a
      paradigm shift in their perioperative management. Cognizant of their detrimental
      effect, the use of large volumes of fresh frozen plasma to correct derangements
      in SLTs has given way to more refined haemostatic management with specific factor
      concentrates guided by VETs, coupled with measures to minimize portal venous
      pressure and meticulous surgical hemostasis.

PMID- 29027775
TI  - Tactics for reducing opioids consumption for bariatric surgery.

PMID- 29027776
TI  - Lung ultrasonography and echocardiography in the Intensive Care Unit: a combined
      and practical approach.
AB  - This article describes some practical applications of critical care
      ultrasonography that are of interest to the frontline intensivist. Instead of
      presenting a standard state of the art review article, we present 3 typical
      clinical cases where combined echocardiography, lung ultrasonography, and other
      ultrasonography techniques were helpful to the critical care team. The manuscript
      includes a variety figures and video clips that illustrate the utility of
      critical care ultrasonography in guiding diagnosis and management of the
      critically ill patient.

PMID- 29027777
TI  - Immobilization during anesthesia for vitrectomy using a laryngeal mask without
      neuromuscular blockade versus endotracheal intubation and neuromuscular blockade.
AB  - BACKGROUND: For intraocular surgery, most authors recommend general anesthesia
      including intubation and neuromuscular blockade to avoid complications by patient
      movements. However, anesthesia using a laryngeal mask and avoidance of muscle
      relaxants is common clinical practice. Purpose of this prospective observational
      study was to compare the incidence of eye movement and deviation of the eye axis
      during general anesthesia adjusted to minimal alveolar concentration (MAC) for
      pars plana-vitrectomy (PPV) using a laryngeal mask without neuromuscular blockade
      (LM) versus endotracheal intubation and neuromuscular blockade (INT). METHODS:
      The patients (N.=148) who underwent PPV for vitreoretinal disorders received MAC
      adjusted general anesthesia by volatile anesthetics. Seventy-four patients were
      subjected to LM and 74 to INT. In both groups the patient's lungs were
      mechanically ventilated without allowing spontaneous ventilation. Eye movements
      and upward deviations were judged and documented during surgery. Postoperatively
      quality of immobilization was assessed by a standardized questionnaire. RESULTS:
      Intraoperative movements were not observed in either group. Upward eye deviation
      was observed in nine (12%) patients in the LM group, but not in patients in the
      INT group (0%; P=0.003). The standardized questionnaire revealed no clinically
      relevant difference in quality of immobilization between groups, especially eye
      deviations did not lead to any relevant surgical complications or difficulties.
      CONCLUSIONS: For PPV, MAC adjusted balanced anesthesia using a laryngeal mask
      without neuromuscular blockade was associated with more, but clinically
      irrelevant upward eye deviations and may be an alternative to intubation with
      neuromuscular blockade. However, adequate depth of anesthesia must be assured to
      avoid unwanted injuries during surgery.

PMID- 29027778
TI  - Automated ventilation: a progress or just another way to do the same?

PMID- 29027779
TI  - Donor lung management.

PMID- 29027780
TI  - Postoperative confusion.

PMID- 29027781
TI  - A smart aid to videolaryngoscopy.

PMID- 29027782
TI  - Improved Performances of LiNi0.8Co0.15Al0.05O2 Material Employing NaAlO2 as a New
      Aluminum Source.
AB  - To prepare a high-performance LiNi0.8Co0.15Al0.05O2 material (LNCA) for Li-ion
      batteries, a new aluminum source, NaAlO2, is employed in the coprecipitation step
      for the first time, and the effect of aluminum sources on the performances is
      systematically investigated. Different from the traditional preparation process
      using Al(NO3)3 as the aluminum source, the preparation process of the
      Ni0.8Co0.15Al0.05(OH)2.05 precursor from NaAlO2 is a hydrolysis process, during
      which the fast precipitation of Al3+ and the formation of a flocculent
      precipitate can be effectively avoided. As expected, stoichiometric LNCA with
      uniform element distribution, low cation mixing and well-ordered layered
      structure is obtained from NaAlO2, which is designed as LNCA-NaAlO2. The
      characterization and electrochemical measurements show that LNCA-NaAlO2 exhibits
      significantly improved performances (such as tap density, initial discharge
      capacity and volumetric energy density, rate performance, cycle performance,
      electrochemical stability, microstructure stability, and storage stability)
      compared to the performances of those prepared from Al(NO3)3 (LNCA-Al(NO3)3),
      indicating that it is an effective strategy to preparing high-performance LNCA
      employing NaAlO2 as the aluminum source.

PMID- 29027783
TI  - Antibacterial Structural Color Hydrogels.
AB  - Structural color hydrogels with lasting survivability are important for many
      applications, but they still lack anti-biodegradation capability. Thus, we herein
      present novel antibacterial structural color hydrogels by simply integrating
      silver nanoparticles (AgNPs) in situ into the hydrogel materials. Because the
      integrated AgNPs possessed wide and excellent antibacterial abilities, the
      structural color hydrogels could prevent bacterial adhesion, avoid hydrogel
      damage, and maintain their vivid structural colors during their application and
      storage. It was demonstrated that the AgNP-tagged poly(N-isopropylacrylamide)
      structural color hydrogels could retain their original thermal-responsive color
      transition even when the AgNP-free hydrogels were degraded by bacteria and that
      the AgNP-integrated self-healing structural color protein hydrogels could save
      their self-repairing property instead of being degraded by bacteria. These
      features indicated that the antibacterial structural color hydrogels could be
      amenable to a variety of practical biomedical applications.

PMID- 29027784
TI  - Mixed-Metal-Organic Framework Self-Template Synthesis of Porous Hybrid
      Oxyphosphides for Efficient Oxygen Evolution Reaction.
AB  - Developing an efficient, stable yet cost-effective electrocatalyst is the key
      link along the path to hydrogen fuels produced by water splitting. The current
      bottleneck in the water electrolysis technology is the sluggish oxygen-evolving
      reaction (OER) which is also central to the rechargeable metal-air batteries.
      Herein, we report a promising mixed-metal-organic framework (MMOF) self-template
      strategy to synthesize CoFe hybrid oxyphosphides with highly porous morphology.
      Aided by the porous hybrid bulk structure beneficial to fast-ion diffusion to
      abundant highly active sites, the as-synthesized Co3FePxO exhibited excellent
      electrocatalytic activity toward OER, with an overpotential of 291 mV at 10 mA cm
      2 and a low Tafel slope of 85 mV dec-1. With the underpinnings of MMOF
      maintaining the structural rigidity and stability, the material also showed long
      life for OER without  discernible activity decay.

PMID- 29027785
TI  - Chemically Cross-Linked MOF Membrane Generated from Imidazolium-Based Ionic
      Liquid-Decorated UiO-66 Type NMOF and Its Application toward CO2 Separation and
      Conversion.
AB  - Carbon dioxide capture and transformation are of great importance to make cuts in
      greenhouse gas emissions. Nanometal-organic frameworks (NMOFs) could serve as
      ideal fillers for polymer membranes owing to their structural diversity and
      regulable microenvironment of the nanocage. Herein, a bifunctional, robust, and
      chemically cross-linked NMOF-based membrane was successfully constructed by the
      postsynthetic polymerization of imidazolium-based ionic liquid (IL)-decorated UiO
      66 type nanoparticles (NPs) and the isocyanate-terminated polyurethane oligomer
      under mild conditions. The IL-modified MOF-polymer membranes exhibit a highly
      selective adsorption for CO2 over N2 and CH4. In addition, the obtained membrane
      can also be a highly active heterogeneous catalyst for CO2 transformation by
      cycloaddition with epoxide under an ambient pressure.

PMID- 29027786
TI  - Hierarchical Porous Magnesium Oxide (Hr-MgO) Microspheres for Adsorption of an
      Organophosphate Pesticide: Kinetics, Isotherm, Thermodynamics, and DFT Studies.
AB  - In this study, hierarchical porous magnesium oxide (Hr-MgO) microspheres have
      been fabricated from a hydromagnesite precursor via a facile precipitation method
      followed by calcination. The Hr-MgO microspheres consist of several nanosheet
      building blocks that generate a flowerlike architecture. Chlorpyrifos (CPF), a
      persistent organic pollutant, has been chosen as a model organophosphate
      pesticide to determine the adsorptive capacities of the fabricated Hr-MgO. The
      equilibrium adsorption data fits well with the Langmuir isotherm model, showing a
      maximum adsorption capacity of 3974 mg g-1, which is the highest value to date.
      Both kinetic as well as thermodynamic parameters reveal the spontaneous,
      exothermic, and pseudo-second-order nature of the adsorption process due to
      chemisorption between the pesticide and the adsorbent. Density functional theory
      studies suggest the importance of hydroxylation on the MgO surface for the
      successful destructive adsorption, which takes place via the cleavage of S?P and
      Cl-C bonds resulting in the fragmentation of CPF, which is in good agreement with
      Fourier transform infrared and mass spectrometric studies. The present study
      shows the potential use of hierarchically structured porous MgO microspheres as
      an efficient adsorbent for the removal of CPF pollutant.

PMID- 29027787
TI  - Detection of T4 Polynucleotide Kinase via Allosteric Aptamer Probe Platform.
AB  - As a vital enzyme in DNA phosphorylation and restoration, T4 polynucleotide
      kinase (T4 PNK) has aroused great interest in recent years. Therefore, numerous
      strategies have been established for highly sensitive detection of T4 PNK based
      on diverse signal amplification techniques. However, they often need
      sophisticated design, a variety of auxiliary reagents and enzymes, or cumbersome
      manipulations. We have designed a new kind of allosteric aptamer probe (AAP)
      consisting of streptavidin (SA) aptamer and the complementary DNA (cDNA) for
      simple detection of T4 PNK without signal amplification and with minimized
      interference in complex biological samples. When the 5'-terminus of the cDNA is
      phosphorylated by T4 PNK, the cDNA is degraded by lambda exonuclease to release
      the fluorescein amidite (FAM)-labeled SA aptamer, which subsequently binds to
      streptavidin beads. The enhancement of the fluorescence signal on SA beads can be
      detected precisely and easily by a microscope or flow cytometer. Our method
      performs well in complex biological samples as a result of the enrichment of the
      signaling molecules on beads, as well as simple manipulations to discard the
      background interference and nonbinding molecules. Without signal amplification
      techniques, our AAP method not only avoids complicated manipulations but also
      decreases the time required. With the advantages of ease of operation,
      reliability, and robustness for T4 PNK detection in buffer as well as real
      biological samples, the AAP has great potential for clinical diagnostics,
      inhibitor screening, and drug discovery.

PMID- 29027789
TI  - Integrated Bacterial Identification and Antimicrobial Susceptibility Testing
      Using PCR and High-Resolution Melt.
AB  - Accurate and timely diagnostics are critical for managing bacterial infections.
      The current gold standard, culture-based diagnostics, can provide clinicians with
      comprehensive diagnostic information including bacterial identity and
      antimicrobial susceptibility, but they often require several days of turnaround
      time, which leads to compromised clinical outcome and promotes the spread of
      antibiotic resistance. Nucleic acid amplification tests such as PCR have
      significantly accelerated the detection of specific bacteria but generally lack
      the capacities for broad-based bacterial identification or antimicrobial
      susceptibility testing. Here, we report an integrated assay based on PCR and high
      resolution melt (HRM) for rapid diagnosis for bacterial infections. In our assay,
      we measure bacterial growth in the presence or absence of certain antibiotics
      with real-time quantitative PCR or digital PCR to determine antimicrobial
      susceptibility. In addition, we use HRM and a machine learning algorithm to
      identify bacterial species based on melt-curve profiles of the 16S rRNA gene in
      an automated fashion. As a demonstration, we correctly identified the bacterial
      species and their antimicrobial susceptibility profiles for multiple unknown
      samples in blinded tests within ~6.5 h.

PMID- 29027790
TI  - Microbial Fermentation of Organic Carbon Substrates Drives Rapid pH
      Neutralization and Element Removal in Bauxite Residue Leachate.
AB  - Globally, mineral processing activities produce an estimated 680 GL/yr of
      alkaline wastewater. Neutralizing pH and removing dissolved elements are the main
      goals of wastewater treatment prior to discharge. Here, we present the first
      study to explicitly evaluate the role of microbial communities in driving pH
      neutralization and element removal in alkaline wastewaters by fermentation of
      organic carbon, using bauxite residue leachate as a model system, and evaluate
      the effects of organic carbon complexity and microbial inoculum addition rates on
      the performance of these treatment systems at laboratory scale. Rates and extents
      of pH neutralization were higher in bioreactors fed with simpler organic carbon
      substrates (glucose and banana: 6 days to reach pH <= 8) than those fed with more
      complex organic carbon substrates (eucalyptus mulch: 15 days to reach pH <= 8;
      woodchips: equilibrium pH around 9). Concentrations of dissolved Al, As, B, Mo,
      Na, S, and V all significantly decreased after bioremediation. Increasing soil
      inoculant addition rate accelerated rates and extent of pH neutralization and
      element removal up to 0.1 wt %; further increases had little effect. Overall,
      glucose added at 1.8 wt % and soil inoculum added at 0.1 wt % provided the most
      effective minimal combination of carbon substrate and inoculum to drive pH
      neutralization and element removal.

PMID- 29027792
TI  - Multifunctional Cytochrome c: Learning New Tricks from an Old Dog.
AB  - Cytochrome c (cyt c) is a small soluble heme protein characterized by a
      relatively flexible structure, particularly in the ferric form, such that it is
      able to sample a broad conformational space. Depending on the specific
      conditions, interactions, and cellular localization, different conformations may
      be stabilized, which differ in structure, redox properties, binding affinities,
      and enzymatic activity. The primary function is electron shuttling in oxidative
      phosphorylation, and is exerted by the so-called native cyt c in the
      intermembrane mitochondrial space of healthy cells. Under pro-apoptotic
      conditions, however, cyt c gains cardiolipin peroxidase activity, translocates
      into the cytosol to engage in the intrinsic apoptotic pathway, and enters the
      nucleus where it impedes nucleosome assembly. Other reported functions include
      cytosolic redox sensing and involvement in the mitochondrial oxidative folding
      machinery. Moreover, post-translational modifications such as nitration,
      phosphorylation, and sulfoxidation of specific amino acids induce alternative
      conformations with differential properties, at least in vitro. Similar structural
      and functional alterations are elicited by biologically significant electric
      fields and by naturally occurring mutations of human cyt c that, along with
      mutations at the level of the maturation system, are associated with specific
      diseases. Here, we summarize current knowledge and recent advances in
      understanding the different structural, dynamic, and thermodynamic factors that
      regulate the primary electron transfer function, as well as alternative functions
      and conformations of cyt c. Finally, we present recent technological applications
      of this moonlighting protein.

PMID- 29027794
TI  - Artificial Metalloproteins for Binding and Stabilization of a Semiquinone
      Radical.
AB  - The interaction of a number of first-row transition-metal ions with a 2,2'
      bipyridyl alanine (bpyA) unit incorporated into the lactococcal multidrug
      resistance regulator (LmrR) scaffold is reported. The composition of the active
      site is shown to influence binding affinities. In the case of Fe(II), we
      demonstrate the need of additional ligating residues, in particular those
      containing carboxylate groups, in the vicinity of the binding site. Moreover,
      stabilization of di-tert-butylsemiquinone radical (DTB-SQ) in water was achieved
      by binding to the designed metalloproteins, which resulted in the radical being
      shielded from the aqueous environment. This allowed the first characterization of
      the radical semiquinone in water by resonance Raman spectroscopy.

PMID- 29027793
TI  - Pivotal Roles of Metal Oxides in the Formation of Environmentally Persistent Free
      Radicals.
AB  - Environmentally persistent free radicals (EPFRs) are emerging pollutants that can
      adversely affect human health. Although the pivotal roles of metal oxides in EPFR
      formation have been identified, few studies have investigated the influence of
      the metal oxide species, size, or concentration on the formation of EPFRs. In
      this study, EPFR formation from a polyaromatic hydrocarbon with chlorine and
      hydroxyl substituents (2,4-dichloro-1-naphthol) was investigated using electron
      paramagnetic resonance spectroscopy. The effect of the metal oxide on the EPFR
      species and its lifetime and yield were evaluated. The spectra obtained with
      catalysis by CuO, Al2O3, ZnO, and NiO were obviously different, indicating that
      different EPFRs formed. The abilities of the metal oxides to promote EPFR
      formation were in the order Al2O3 > ZnO > CuO > NiO, which were in accordance
      with the oxidizing strengths of the metal cations. A decay study showed that the
      generated radicals were persistent, with a maximum 1/e lifetime of 108 days on
      the surface of Al2O3. The radical yields were dependent on the concentration and
      particle size of the metal oxide. Metal oxide nanoparticles increased the EPFR
      concentrations more than micrometer-sized particles.

PMID- 29027795
TI  - Photochromic Heterocycle-Fused Thieno[3,2-b]phosphole Oxides as Visible Light
      Switches without Sacrificing Photoswitching Efficiency.
AB  - A series of novel photochromic thieno[3,2-b]phosphole oxides has been shown to
      demonstrate photochromism without the need for the use of high-energy ultraviolet
      (UV) light irradiation while maintaining promising photochromic properties such
      as excellent thermal irreversibility, robust fatigue resistance, and high
      photoswitching efficiency. Promising visible light-induced photochromic
      properties have been realized by the new molecular design, in which various pi
      systems have been incorporated into the weakly aromatic phosphole backbone
      instead of the conventional modification of the peripheral diaryl units that
      usually leads to a drastic reduction of the photochromic quantum yields (phiO->C
      and phiC->O < 0.01) or even a loss of the photochromic behavior. Excellent
      fatigue resistance has been observed for a representative compound with no
      apparent loss of photochromic reactivity over ten photochromic cycles by
      alternate irradiation with violet (ca. 410 nm) and green (ca. 500 nm) light with
      high photochromic quantum yields (phiO->C = 0.87 and phiC->O = 0.44), rendering
      it a new promising candidate as visible light photoswitches for various potential
      applications.

PMID- 29027796
TI  - Changing Single-Molecule Magnet Properties of a Windmill-Like Distorted
      Terbium(III) alpha-Butoxy-Substituted Phthalocyaninato Double-Decker Complex by
      Protonation/Deprotonation.
AB  - Synthesis, structures, and magnetic properties of alpha-butoxy-substituted
      phthalocyaninato double-decker complexes Tb(alpha-obPc)2 (1-) (alpha-obPc:
      dianion of 1,4,8,11,15,18,22,25-octa(n-butoxy)phthalocyaninato) with protonated
      (1H), deprotonated (1[HDBU]), and diprotonated forms (1H2+) are discussed. X-ray
      analysis was used to confirm the position of the proton in 1H, and it was
      revealed that the protonation induced asymmetric distortion in 1H. In contrast,
      1[HDBU] was distorted in a highly symmetric windmill-like fashion. 1H is arranged
      in a slipped column array in the crystal packing, whereas 1[HDBU] is arranged in
      a one-dimensional fashion, in which the magnetic easy axes of 1[HDBU] lie along
      the same line. From direct-current (dc) magnetic measurements, ferromagnetic Tb
      Tb interactions occur in both 1H and 1[HDBU], and magnetic hysteresis was
      observed. However, the area of the magnetic hysteresis in 1[HDBU] is larger than
      that in 1H, meaning that magnetic relaxation time (tau) is longer in 1[HDBU]. In
      addition, the results of alternating-current magnetic measurements in a zero dc
      magnetic field indicate that tau of 1[HDBU] is longer as compared to 1H. In other
      words, protonation/deprotonation affects not only the molecular structures and
      crystal packing but also the single-molecule magnet properties.

PMID- 29027797
TI  - Phosphorus-Chalcogen Ring Expansion and Metal Coordination.
AB  - The reactivity of 4-membered (RPCh)2 rings (Ch = S, Se) that contain phosphorus
      in the +3 oxidation state is reported. These compounds undergo ring expansion to
      (RPCh)3 with the addition of a Lewis base. The 6-membered rings were found to be
      more stable than the 4-membered precursors, and the mechanism of their formation
      was investigated experimentally and by density functional theory calculations.
      The computational work identified two plausible mechanisms involving a
      phosphinidene chalcogenide intermediate, either as a free species or stabilized
      by a suitable base. Both the 4- and 6-membered rings were found to react with
      coinage metals, giving the same products: (RPCh)3 rings bound to the metal center
      from the phosphorus atom in tripodal fashion.

PMID- 29027798
TI  - Correction to Naphthoquinones of Sinningia reitzii and Anti
      inflammatory/Antinociceptive Activities of 8-Hydroxydehydrodunnione.

PMID- 29027799
TI  - Proton-Coupled O-Atom Transfer in the Oxidation of HSO3- by the Ruthenium Oxo
      Complex trans-[RuVI(TMC)(O)2]2+ (TMC = 1,4,8,11-Tetramethyl-1,4,8,11
      tetraazacyclotetradecane).
AB  - We have previously reported that the oxidation of SO32- to SO42- by a trans
      dioxoruthenium(VI) complex, [RuVI(TMC)(O)2)]2+ (RuVI; TMC = 1,4,8,11-tetramethyl
      1,4,8,11-tetraazcyclotetradecane) in aqueous solutions occurs via an O-atom
      transfer mechanism. In this work, we have reinvestigated the effects of the pH on
      the oxidation of SIV by RuVI in more detail in order to obtain kinetic data for
      the HSO3- pathway. The HSO3- pathway exhibits a deuterium isotope effect of 17.4,
      which indicates that O-H bond breaking occurs in the rate-limiting step. Density
      functional theory calculations have been performed that suggest that the
      oxidation of HSO3- by RuVI may occur via a concerted or stepwise proton-coupled O
      atom transfer mechanism.

PMID- 29027800
TI  - Chromophore Distortions in Photointermediates of Proteorhodopsin Visualized by
      Dynamic Nuclear Polarization-Enhanced Solid-State NMR.
AB  - Proteorhodopsin (PR) is the most abundant retinal protein on earth and functions
      as a light-driven proton pump. Despite extensive efforts, structural data for PR
      photointermediate states have not been obtained. On the basis of dynamic nuclear
      polarization (DNP)-enhanced solid-state NMR, we were able to analyze the retinal
      polyene chain between positions C10 and C15 as well as the Schiff base nitrogen
      in the ground state in comparison to light-induced, cryotrapped K- and M-states.
      A high M-state population could be achieved by preventing reprotonation of the
      Schiff base through a mutation of the primary proton donor (E108Q). Our data
      reveal unexpected large and alternating 13C chemical shift changes in the K-state
      propagating away from the Schiff base along the polyene chain. Furthermore, two
      different M-states have been observed reflecting the Schiff base reorientation
      after the deprotonation step. Our study provides novel insight into the
      photocycle of PR and also demonstrates the power of DNP-enhanced solid-state NMR
      to bridge the gap between functional and structural data and models.

PMID- 29027801
TI  - Palladium(0)-Catalyzed Carbonylative One-Pot Synthesis of N-Acylguanidines.
AB  - A convenient synthetic strategy toward N-acylguanidines via a sequential one-pot
      multicomponent carbonylation/amination reaction has been developed. The compounds
      were readily obtained via an N-cyanobenzamide intermediate formed from the Pd(0)
      catalyzed carbonylative coupling of cyanamide and aryl iodides or bromides.
      Subsequent amination with a large variety of amines provided the final N
      acylguanidines, with the overall formation of one C-C and two C-N bonds, in
      moderate to excellent yields. The substrate scope was found to be wide and the
      methodology was used to produce over 50 compounds, including 29 novel molecules.
      Furthermore, three separate nitrogen-containing heterocycles were prepared from
      the N-acylguanidines synthesized using the developed multicomponent,
      carbonylative method.

PMID- 29027802
TI  - Phosphonate-Stabilized Titanium-Oxo Clusters with Ferrocene Photosensitizer:
      Structures, Photophysical and Photoelectrochemical Properties, and DFT/TDDFT
      Calculations.
AB  - The metal-to-core charge transfer (MCCT) transition in sensitized titanium-oxo
      clusters is an important process for photoinduced electron injection in
      photovoltaic conversion. This process resembles most closely the Type II
      photoinjection in dye-sensitized solar cells. Herein we report the synthesis and
      photophysical and photoelectrochemical (PEC) properties of the phosphonate
      stabilized titanium-oxo clusters containing the ferrocenecarboxylate ligands.
      These ferrocene-containing clusters exhibit intense visible absorption extended
      up to 600 nm along with low optical band gaps of ~2.2 eV. The low-energy
      transitions of these clusters were systematically investigated by UV-vis
      spectroscopy and DFT/TDDFT calculations. The combined experimental and
      computational studies suggest that the ferrocenecarboxylate-substituted titanium
      oxo clusters form a donor-acceptor (D-A) system. The low-energy transition of
      these clusters primarily involves the MCCT from the iron center to TiO cluster
      core. The TiO core structure and phosphonate ligands both have great influence on
      the PEC properties of the clusters. This work provides valuable examples for the
      sensitized titanium-oxo clusters in which electron injection takes place via MCCT
      transition.

PMID- 29027803
TI  - Origin of Efficient Inverted Nonfullerene Organic Solar Cells: Enhancement of
      Charge Extraction and Suppression of Bimolecular Recombination Enabled by
      Augmented Internal Electric Field.
AB  - We report our effort to unravel the origin of efficient operation of nonfullerene
      organic solar cells (OSCs), based on a poly[4,8-bis(5-(2-ethylhexyl) thiophen-2
      yl)benzo[1,2-b;4,5-b']dithiophene-2,6-diyl-alt-(4-(2-ethylhexyl)-3
      fluorothieno[3,4-b]thiophene-)-2-carboxylate-2-6-diyl)](PTB7-Th):3,9-bis(2
      methylene-(3-(1,1-dicyanomethylene)-indanone))-5,5,11,11-tetrakis(4-hexylphenyl)
      dithieno[2,3-d:2',3'-d']-s-indaceno [1,2-b:5,6-b']dithiophene (ITIC) blend
      system. The effects of buildup of space charges, charge extraction, and
      bimolecular recombination processes on the performance and the stability of PTB7
      Th:ITIC-based regular and reverse configuration OSCs are analyzed. It is found
      that the high-performing inverted PTB7-Th:ITIC OSCs benefit from the combined
      effects of (1) suppression of bimolecular recombination enabled by an augmented
      effective internal electric field and (2) improvement of charge extraction by
      avoiding the holes passing through ITIC-rich region, which would otherwise occur
      in a regular configuration cell. The inverted PTB7-Th:ITIC OSCs possess a
      significant improvement in the cell stability and a high power conversion
      efficiency of ~8.0%, which is >29% higher than that of an optimized regular
      configuration control cell (6.1%).

PMID- 29027804
TI  - Planar Polycyclic Oxaphosphoranes Incorporating a Benzophosphole Unit.
AB  - A facile method to synthesize quaternized benzophospholes on gram scale was
      reported, and the products were isolated by simple filtration. During this
      research, a series of sigma5-oxaphosphoranes incorporating polycyclic aromatic
      hydrocarbons (PAHs) were obtained. The grafting of alpha-phenolate groups on the
      phosphorus center enhances the coplanarity of the system.

PMID- 29027806
TI  - Clinical evaluation and treatment of phaeochromocytoma.
AB  - Phaeochromocytoma and extra adrenal paraganglioma are rare neuroendocrine tumours
      and have the potential to secrete adrenaline, noradrenaline and dopamine causing
      a myriad of clinical symptoms. Prompt diagnosis is essential for clinicians and
      requires a multidisciplinary specialist approach for the clinical and laboratory
      investigation, diagnosis, treatment and follow-up of patients. This paper is an
      integrated review of the clinical and laboratory evaluation and treatment of
      patients suspected to have phaeochromocytoma or paraganglioma, highlighting
      recent developments and best practices from recent published clinical guidelines.

PMID- 29027805
TI  - Near-Infrared Emissive Discrete Platinum(II) Metallacycles: Synthesis and
      Application in Ammonia Detection.
AB  - Two novel discrete organoplatinum(II) metallacycles are prepared by means of
      coordination-driven self-assembly of a 90 degrees  organoplatinum(II) acceptor,
      cis-(PEt3)2Pt(OTf)2, with two donors, a pyridyl donor, 9,10-di(4
      pyridylvinyl)anthracene, and one of two dicarboxylate ligands. Both metallacycles
      display aggregation-induced emission as well as solvatochromism. More
      interestingly, both metallacycles exhibit near-infrared fluorescent emission in
      the solid state and can be used to detect ammonia gas.

PMID- 29027807
TI  - Biochemistry of the menopause.
AB  - The life of a human female is characterized from teenage years by monthly
      menstruation which ceases (the menopause) typically between the age of 40 and 60
      years. The potential for reproduction declines and ceases as the ovaries become
      depleted of follicles. A transition period in mid-life, for 2 to 10 years, when
      menstruation is less regular is called the perimenopause. The menopause is
      associated with a significant decline in plasma concentrations of sex hormones,
      an increase in the concentrations of the gonadotrophins and changes in other
      hormones such as the inhibins. These changes are superimposed with effects of
      aging, social and metabolic factors, daily activity and well-being. Although the
      menopause is entirely natural, in some cases ovarian failure can occur earlier
      than usual; this is pathological and warrants careful biochemical investigations
      to distinguish it from conditions causing infertility. Elderly females are
      affected by a range of clinical disorders including endocrine, cardiovascular,
      skeletal, urogenital tract and immunological systems, body mass, vasomotor tone,
      mood and sleep pattern. Reference intervals for many diagnostic biochemical tests
      for the menopause need to be used when interpreting results in clinical
      investigations for patient management. The standardization and harmonization of
      assays are being addressed. Many women now choose to develop their career before
      bearing children, and the health service has had to change services around this.
      This review does not cover screening for and tests during pregnancy. The review
      is timely since the population is aging and there will be more demand on
      healthcare services.

PMID- 29027809
TI  - Correction to: J Altern Complement Med 2016;22(12):1007-1012. DOI:
      10.1089/acm.2016.0115.

PMID- 29027808
TI  - Measuring the attitudes of novice drivers with autism spectrum disorder as an
      indication of apprehensive driving: Going beyond basic abilities.
AB  - For some individuals with autism spectrum disorder, driving apprehension may
      interfere with the acquisition and application of driving privileges. The Driving
      Attitude Scale Parent-Report provides an indication of novice drivers' positive
      and negative attitudes toward driving. Responses were compared for parents of 66
      autism spectrum disorder and 166 neuro-typical novice drivers. After the autism
      spectrum disorder drivers completed 3 months of driver training, 60 parents
      repeated the Driving Attitude Scale Parent-Report. Parents reported autism
      spectrum disorder drivers to have less positive and more negative attitudes
      toward driving than parents of neuro-typical drivers. Parents of autism spectrum
      disorder drivers who received driving training in a safe/low-threat virtual
      reality driving simulator demonstrated a significant increase in positive
      attitudes and reduction in negative attitudes, compared to parents of autism
      spectrum disorder drivers undergoing routine driver training. The reports of
      parents of autism spectrum disorder drivers suggest potential problems with
      learning to drive that can go beyond general abilities and include driving
      apprehension.

PMID- 29027810
TI  - Electrocardiographic characteristics associated with in-hospital outcome in
      patients with left main acute coronary syndrome: For contriving a new risk
      stratification score.
AB  - AIM: The aim of this study was to evaluate electrocardiographic characteristics
      associated with in-hospital prognosis in patients with left main acute coronary
      syndrome. METHODS AND RESULTS: A total of 89 left main acute coronary syndrome
      subjects were selected from 3357 consecutive acute coronary syndrome patients
      (2.7%). Patients of this study were divided into two groups; those who survived
      and those who died. Patients' characteristics and electrocardiogram on admission
      were then retrospectively analyzed between the two groups. In-hospital mortality
      was 28.1%. The prevalence and degree of ST-segment elevation at lead aVL were
      significantly higher in the deceased group than in the survival group ( p<0.001).
      However, those at lead aVR did not show significant differences between the two
      groups. Moreover, the width of the QRS-complex was significantly wider (lead V3;
      p<0.001), and the level of five minus the absolute value of five minus number of
      ST-segment elevation (5-|5-ST|; due to the highest in-hospital mortality (70%) in
      the five-lead ST-segment elevation group) was significantly larger in the
      deceased group than in the survival group ( p<0.001). The odds ratios that
      predicted in-hospital cardiac death were 1.03 for width of the QRS-complex at
      lead V3 (95% confidence interval (CI); 1.01-1.06; p=0.003), 1.74 for 5-|5-ST|
      (95% CI; 1.03-3.00; p=0.040), and 1.44 for ST-segment elevation at lead aVL (95%
      CI; 0.93-2.23; p=0.100). CONCLUSIONS: ST-segment elevation at lead aVL rather
      than aVR, width of the QRS-complex at lead V3 and number of ST-segment elevation
      were the prognostic predictors for in-hospital mortality in patients with left
      main acute coronary syndrome. Electrocardiographic characteristics should be
      assessed in addition to the established risk score in patients with left main
      acute coronary syndrome.

PMID- 29027811
TI  - Prevention of human papillomavirus (HPV)-related tumors in people living with
      human immunodeficiency virus (HIV).
AB  - INTRODUCTION: In comparison to their HIV-negative counterparts, people living
      with HIV (PLWH) have a higher prevalence of human papillomavirus (HPV) infection
      in various anatomical sites coupled with increased HPV persistence, higher risk
      of HPV-related tumors, and faster disease progression. Areas covered: Gender
      neutral prevention strategies for HPV-related cancers in PLWH discussed: ABC
      approach, HPV vaccination, antiretroviral treatment (ART), anal cancer screening,
      and smoking cessation. Gender specific strategies: cervical cancer screening
      reduces the incidence and mortality of cervical cancer and circumcision might
      reduce the risk of HPV infections in men. Expert commentary: HPV-related cancer
      incidence has not declined (e.g. cervical cancer) and has even increased (e.g.
      anal cancer) in the ART era, demanding an effective HPV prevention strategy. HPV
      vaccination should be introduced into national prevention programs worldwide
      immediately because current prophylactic vaccines are safe, tolerable, and
      immunogenic in PLWH. HPV vaccine efficacy trials in PLWH are essential to
      determine the most appropriate immunization schedule. The population most at risk
      of anal cancer is HIV-positive men who have sex with men, who are not protected
      by herd immunity if only the female population is vaccinated. Unvaccinated PLWH
      need enhanced surveillance for early detection of HPV-related cancers and their
      precursors.

PMID- 29027813
TI  - Final chapter, From India to the Planet Mars: A Study of a Case of Somnambulism
      with Glossolalia, by Theodore Flournoy (1900).
AB  - Among the many attempts to explain mediumship psychologically at the turn of the
      century were the efforts of Swiss psychologist Theodore Flournoy (1854-1920). In
      his well-known book Des Indes a la Planete Mars (1900), translated as From India
      to the Planet Mars (1900), Flournoy analysed the mediumistic productions of
      medium Helene Smith (1861-1929), consisting of accounts of previous lives in
      France and in India, and material about planet Mars. Flournoy explained the
      phenomena as a function of cryptomnesia, suggestive influences, and subconscious
      creativity, analyses that influenced both psychology and psychical research. The
      purpose of this Classic Text is to reprint the conclusion of Flournoy's study,
      whose ideas were developed in the context of psychological attention to
      mediumship and secondary personalities.

PMID- 29027812
TI  - Use of a Novel, Remotely Connected Diabetes Management System Is Associated with
      Increased Treatment Satisfaction, Reduced Diabetes Distress, and Improved
      Glycemic Control in Individuals with Insulin-Treated Diabetes: First Results from
      the Personal Diabetes Management Study.
AB  - BACKGROUND: The ability to automatically transfer data to clinicians and receive
      timely guidance in therapy adjustments through remote and in-office consults can
      positively impact patients' perceptions about quality of care, which is
      positively associated with clinical outcomes. We assessed the impact of using the
      Accu-Chek Connect diabetes management system on treatment satisfaction, diabetes
      distress, and glycemic control in adults with type 1 diabetes and insulin-treated
      type 2 diabetes. SUBJECTS AND METHODS: This 6-month, prospective, multicenter,
      single-arm study assessed the impact of using the system on treatment
      satisfaction and glycemic control among 87 adults with insulin-treated diabetes
      (multiple daily insulin injections and basal only), with 8.8% +/- 1.6% glycated
      hemoglobin (HbA1c) at baseline. The Diabetes Treatment Satisfaction Questionnaire
      status (DTSQs) and Diabetes Distress Scale (DDS) were administered at baseline,
      and the Diabetes Treatment Satisfaction Questionnaire-change (DTSQc) and DDS at 6
      months. Changes in HbA1c, average blood glucose (BG), and other metrics were also
      assessed. RESULTS: Improvements in DTSQc scores were observed at 6 months with a
      total mean (standard deviation) score of 14.3 +/- 5.1. Significant reductions in
      total mean DDS scores from baseline to 6 months were also observed, from 2.0 +/-
      0.8 to 1.7 +/- 0.7, P < 0.0001. A significant reduction in regimen-related
      distress was notable, from "moderate distress" (2.4 +/- 1.0) to "not distressed"
      (1.9 +/- 0.9), P < 0.0001). Significant reductions in mean HbA1c (-0.9 +/- 1.6, P
      < 0.0001) and mean BG (-24.8 +/- 50.8, P < 0.0001) were observed. CONCLUSIONS:
      Use of the Accu-Chek Connect diabetes management system is associated with
      increased treatment satisfaction and improved glycemic control among individuals
      with insulin-treated diabetes. NCT02600845 ( www.clinicaltrials.gov ).

PMID- 29027814
TI  - Short-chain fatty acids: a link between prebiotics and microbiota in chronic
      kidney disease.
AB  - Under physiologic conditions, the human gut microbiota performs several
      activities essential to the body health. In contrast, their imbalances exacerbate
      some actions which can promote a cascade of metabolic abnormalities, and vice
      versa. Numerous diseases, including chronic kidney disease, are associated with
      gut microbiota imbalance, and among several strategies to re-establish gut
      symbiosis, prebiotics seem to represent an effective nonpharmacological approach.
      Prebiotics fermentation by gut microbiota produce short-chain fatty acids, which
      improve the gut barrier integrity and function, and modulate the glucose and
      lipid metabolism as well as the inflammatory response and immune system.
      Therefore, this literature review intends to discuss the beneficial effects of
      prebiotics in human health through short-chain fatty acids production, with a
      particular interest on chronic kidney disease.

PMID- 29027815
TI  - l-Carnosine As an Adjunctive Therapy to Risperidone in Children with Autistic
      Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.
AB  - OBJECTIVES: This study aimed at investigating the efficacy and tolerability of l
      carnosine as an add-on to risperidone in the management of children with autism.
      METHODS: This was a 10-week, randomized, double-blind, placebo-controlled study.
      Seventy drug-free children aged 4-12 years old with a diagnosis of autism
      spectrum disorder (ASD), according to the Diagnostic and Statistical Manual of
      Mental Disorders, fifth edition. (DSM-5) who had an Aberrant Behavior Checklist
      Community (ABC-C) scale irritability subscale score of >=12, entered the study.
      The patients were randomly assigned to l-carnosine (800 mg/day in 2 divided
      doses) or placebo in addition to risperidone titrated up to 2 mg/day (based on
      body weight) for 10 weeks. The children were assessed by using ABC-C at baseline
      and weeks 5 and 10 post-baseline. The primary outcome measure was the mean change
      in the ABC-C irritability subscale score, and other subscale scores were defined
      as secondary outcomes. RESULTS: Using the general linear model repeated measures,
      no significant effect was observed for time * treatment interaction on the
      irritability subscale scores. However, significant effect was detected on the
      hyperactivity/noncompliance subscale [F (1.62, 64.96) = 3.53, p-value = 0.044].
      No significant improvements were obtained on the lethargy/social withdrawal,
      stereotypic behavior, and inappropriate speech subscale scores. Significantly
      greater score reduction in the hyperactivity/noncompliance subscale occurred in
      the l-carnosine group compared with the placebo group at the end of the trial.
      Extrapyramidal Symptom Rating Scale Scores and its changes did not differ between
      the two groups. The frequency of other side effects was not significantly
      different between the two groups. CONCLUSIONS: Although no significant difference
      was detected on the irritability subscale scores, l-carnosine add-on can improve
      hyperactivity/noncompliance subscales of the ABC-C rating scale in patients with
      ASD.

PMID- 29027816
TI  - A comparison of the genetic and clinical risk factors for arterial hypertension
      between indigenous and non-indigenous people of the Shoria Mountain Region.
AB  - BACKGROUND: This study investigated the non-genetic and genetic risk factors for
      arterial hypertension (AH) in two ethnic groups living in the Mountain Shoria
      region: Shors and non-indigenous people. METHODS: Clinical and epidemiological
      study of compactly living population in the remote areas of the Mountain Shoria
      (Orton, Ust-Kabyrza, Sheregesh settlements, Kemerovo region). 1178 residents of
      these settlements were surveyed with the help of continuous sampling method; the
      sample consisted of adults (18 years and older). RESULTS: The prevalence of AH
      was lower in Shors (39.9% vs. 46.1%), mainly due to differences between men from
      the different groups: 33.2% vs. 45.8%. The percentage of people with AH,
      overweight, and obesity (including transabdominal obesity) in the different age
      groups did not differ between ethnicities. We identified statistically
      significant differences in the prevalence of hypertension according the two ethic
      groups according to age, body weight, and abdominal obesity. I/D ACE and ADRA2B
      polymorphisms were associated with AH. In DD ACE and DD ADRA2B carriers, there
      were fewer hypertensive patients in Shors than in non-indigenous people: 40.6%
      vs. 58.6% and 38.3% vs. 64.0%, respectively. In DD ACE carriers, more Shors had
      AH (60.0% vs. 37.1%). CONCLUSION: Among Shors, the following factors increased AH
      risk: female sex, age, hypercholesterolemia, hyperbetacholesterinemia,
      hypertriglyceridemia, obesity (including transabdominal obesity), glucose
      intolerance, and the DD ACE, CT MTHFR, and AA ADRB1 genotypes; among the non
      indigenous population, the main factors were age, hypercholesterolemia,
      hyperbetacholesterinemia, hypoalfacholesterinemia, hypertriglyceridemia, obesity
      (including transabdominal obesity), and ID ACE genotype.

PMID- 29027817
TI  - Oral Supplementation of Parturient Mothers with Vitamin D and Its Effect on 25OHD
      Status of Exclusively Breastfed Infants at 6 Months of Age: A Double-Blind
      Randomized Placebo Controlled Trial.
AB  - BACKGROUND: Exclusively breastfed infants are at increased risk of vitamin D
      deficiency and many lactating mothers have been found deficient in 25OHD stores.
      OBJECTIVE: To compare serum vitamin D levels in exclusively breastfed infants at
      6 months of age with or without oral supplementation of 600,000 IU of vitamin D3
      to mothers in early postpartum period. METHODS: Exclusively breastfeeding term
      parturient mothers were randomized 24-48 hours following delivery to receive
      either 600,000 IU of vitamin D3 (Cholecalciferol) over 10 days in a dose of
      60,000 IU/day or placebo. 25OHD levels were measured by Radio Immuno Assay method
      at recruitment and after 6 months in all mothers and their infants. Urinary
      calcium and creatinine ratio was measured to monitor adverse effects of vitamin
      D3 in both mothers and infants at 14 weeks and 6 months of age. X-ray of both
      wrists in anteroposterior view and serum alkaline phosphatase of infants were
      done in both groups at 6 months of age to look for evidence of rickets. RESULTS:
      Maternal profile was similar in intervention (A) and control (B) groups. Mothers'
      serum 25OHD levels at recruitment were also similar being 16.2 +/- 9.3 ng/mL in
      group A and 14.1 +/- 7.1 ng/mL in group B. After 6 months, 25OHD levels were 40.3
      +/- 21.6 and 22.9 +/- 20.1 ng/mL in group A and group B mothers (p <= 0.00),
      respectively. The serum 25OHD levels in cord blood were 9.9 +/- 5.7 and 8.9 +/-
      5.1 ng/mL, respectively, in infants born to mothers in intervention and control
      groups (p = 0.433). At 6 months of age, the serum 25OHD levels significantly (p <
      0.00) raised to 29.1 +/- 14.6 ng/mL in infants of group A compared to those of
      group B (15.7 +/- 17.7 ng/mL). Four infants developed radiological rickets at 6
      months of age, two infants each in intervention group and study group. As against
      10 infants in the control group (16.94%), no infant in the study group had
      biochemical rickets. Urinary calcium and creatinine ratio in mothers and infants
      at 14 weeks and 6 months of age in both intervention and study group was within
      normal limits, indicating there was no adverse effects of oral administration of
      600,000 IU of vitamin D3. CONCLUSION: Serum 25OHD levels of exclusively breastfed
      infants significantly rise at 6 months of age when their mothers are orally
      supplemented with 60,000 IU of vitamin D3 daily for 10 days in the early
      postpartum period in comparison to infants of vitamin D3 unsupplemented mothers.

PMID- 29027818
TI  - Effects of nesfatin-1 on atrial contractility and thoracic aorta reactivity in
      male rats.
AB  - BACKGROUND: This study aimed to examine the effects of nesfatin-1 on thoracic
      aorta vasoreactivity and to investigate the inotropic and chronotropic effects of
      nesfatin-1 on the spontaneous contractions of the isolated rat atria. METHODS:
      Isolated right atria and thoracic aorta were used in organ baths. The reactivity
      of the thoracic aorta was evaluated by potassium chloride (KCl), phenylephrine
      (Phe), acetylcholine (ACh), and sodium nitroprusside (SNP). The effects of
      nesfatin-1 on the spontaneous contractions of the rat atria were also examined.
      RESULTS: Nesfatin-1 (0.1-100 ng/ml) produced a concentration-dependent relaxation
      response in rat thoracic aorta. The relaxant responses to nesfatin-1 were
      inhibited by the removal of endothelium, NO synthase blocker N-nitro-L-arginine
      methyl ester (L-NAME, 10-4 M), and soluble guanylate cyclase inhibitor 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10-5 M). Nesfatin-1 (10 ng/ml, 30
      min) increased the relaxation responses to either ACh or SNP, and the contractile
      response to both Phe and KCl did not significantly change in the arteries that
      were incubated with nesfatin-1 compared with the controls. The thoracic aorta
      contractions induced by the stepwise addition of Ca2+ to a high KCl solution with
      no Ca2+ were not significantly changed by nesfatin-1. Under calcium-free
      conditions, the contractions of the thoracic aorta rings incubated with nesfatin
      1 in response to Phe were not significantly lower than those of the rings from
      the control rats. Nesfatin-1 showed positive inotropic and chronotropic effects
      on rat atria. CONCLUSION: Nesfatin-1 significantly changed the vascular
      responsiveness in rat thoracic aorta and produced positive inotropic and
      chronotropic effects on rat atria.

PMID- 29027819
TI  - Can phage therapy solve the problem of recalcitrant chronic rhinosinusitis?
AB  - Chronic rhinosinusitis (CRS) affects 5-15% of the global population. In some
      patients, the infectious exacerbations of the disease are recalcitrant to medical
      treatment and surgery. These cases are probably associated with the presence of
      bacterial biofilms. Bacteriophage (phage) therapy seems to be a promising
      antibiofilm strategy. The efficacy of phage therapy in sinonasal infections has
      been demonstrated both in vitro and in animal models. In the past, phage
      preparations were also administered to humans with CRS with favorable outcomes
      and no significant side effects. Very recently, the safety and efficacy of phage
      therapy in otolaryngological infections has been demonstrated in pioneer Phase
      I/II clinical trials. This review addresses the potential of phage therapy to
      treat CRS. We also discuss issues that require further research.

PMID- 29027820
TI  - Using Cost-Effectiveness Analysis to Quantify the Value of Genomic-Based
      Diagnostic Tests: Recommendations for Practice and Research.
AB  - AIMS: New sequencing technologies allow increased opportunities to use genomic
      based diagnostic tests (genomic tests) in routine clinical practice, which will
      impact healthcare budgets and patients' outcomes. This article aims to generate a
      list of recommendations on how the principles and methods of cost-effectiveness
      analysis (CEA) can be used to quantify the costs and benefits of genomic tests.
      METHODS: A systematic literature search identified publications describing the
      use of CEA to evaluate genomic tests. Data were extracted as key concepts to
      produce a thematic list of previously described challenges and solutions to using
      CEA to evaluate genomic tests. Defining features of evaluating genomic tests were
      categorized into a list of key recommendations for applying methods in practice
      and for research needs. RESULTS: Features producing challenges in the
      implementation of CEA to evaluate genomic tests were as follows: the ability of
      the tests to diagnose multiple disorders; potential consequences for future
      generations suggesting an infinite time horizon; and the potential need to
      consider nonhealth benefits. CONCLUSIONS: CEA was identified as an appropriate
      evaluative framework for genomic tests, although standard methods may need
      modification and important method research questions remain. Key recommendations
      suggest a need for research to reflect: sharing genomic information across
      generations; genomic tests for multiple disorders; and health and nonhealth
      benefits.

PMID- 29027821
TI  - It is dopey to stop giving dopamine to hospitalized patients with Parkinson's
      disease.

PMID- 29027822
TI  - Mucosa-associated lymphoid tissue lymphoma with intraocular and orbital
      involvement: case presentation and review of the literature.
AB  - Primary ocular lymphomas are typically confined to either the eye or the orbit.
      Rarely, in immune-competent patients, lymphomas affect both the eye and the orbit
      simultaneously. Mucosa-associated lymphoid tissue (MALT) lymphomas are the most
      common ocular lymphomas. They usually present primarily in the orbit but
      sometimes can present primarily in intraocular tissue. MALT lymphomas that occur
      initially in the uvea can sometimes spread to the adjacent orbit. We report a
      case of progressively enlarging MALT lymphoma in a 62-year-old immune-competent
      patient causing a severe mass effect in the orbit and simultaneously presenting
      with intraocular involvement. There was radiographic evidence of lymphoma
      confined to the orbit with intraocular involvement. The simultaneous presentation
      makes it difficult to determine if the lymphoma initially presented in the orbit
      or intraocular tissue, although the orbital component was more impressive. The
      case also includes a literature review of simultaneous orbital and intraocular
      MALT lymphomas. The patient responded to systemic chemotherapy with regression in
      size of the lymphoma, relief of the mass effect seen in the orbit, and the
      regression of the intraocular involvement.

PMID- 29027823
TI  - Structural and biological diversity of natural p-terphenyls.
AB  - p-Terphenyls consisting of a C-18 tricyclic or polycyclic C-18 aromatic skeleton,
      have diverse structures because of the variation of the middle ring and the
      connections between the rings, and to the main skeleton. p-Terphenyls have
      recently been found to exhibit various biological activities such as cytotoxic,
      alpha-glucosidase inhibitory, antioxidant, and antimicrobial activity. In this
      review, we briefly summarized the structural varieties, biosyntheses, and
      bioactivities of natural p-terphenyl derivatives referring to the recent 10
      years' publications.

PMID- 29027824
TI  - A computable phenotype for asthma case identification in adult and pediatric
      patients: External validation in the Chicago Area Patient-Outcomes Research
      Network (CAPriCORN).
AB  - OBJECTIVE: Comprehensive, rapid, and accurate identification of patients with
      asthma for clinical care and engagement in research efforts is needed. The
      original development and validation of a computable phenotype for asthma case
      identification occurred at a single institution in Chicago and demonstrated
      excellent test characteristics. However, its application in a diverse payer mix,
      across different health systems and multiple electronic health record vendors,
      and in both children and adults was not examined. The objective of this study is
      to externally validate the computable phenotype across diverse Chicago
      institutions to accurately identify pediatric and adult patients with asthma.
      METHODS: A cohort of 900 asthma and control patients was identified from the
      electronic health record between January 1, 2012 and November 30, 2014. Two
      physicians at each site independently reviewed the patient chart to annotate
      cases. RESULTS: The inter-observer reliability between the physician reviewers
      had a kappa-coefficient of 0.95 (95% CI 0.93-0.97). The accuracy, sensitivity,
      specificity, negative predictive value, and positive predictive value of the
      computable phenotype were all above 94% in the full cohort. CONCLUSIONS: The
      excellent positive and negative predictive values in this multi-center external
      validation study establish a useful tool to identify asthma cases in in the
      electronic health record for research and care. This computable phenotype could
      be used in large-scale comparative-effectiveness trials.

PMID- 29027825
TI  - Cost-effectiveness of carfilzomib plus dexamethasone compared with bortezomib
      plus dexamethasone for patients with relapsed or refractory multiple myeloma in
      the United States.
AB  - BACKGROUND: We assessed the economic value of carfilzomib 56 mg/m2 and
      dexamethasone (Kd56) vs. bortezomib and dexamethasone (Vd) for
      relapsed/refractory multiple myeloma (R/RMM) using ENDEAVOR trial results.
      METHODS: Cost-effectiveness of Kd56 vs. Vd was assessed using a partitioned
      survival model by estimating progression-free survival, overall survival, and
      direct costs over a lifetime horizon. Surveillance Epidemiology and End Results
      (SEER) survival data were extrapolated after matching registry and ENDEAVOR
      patients. Utilities were sourced from the literature and mapped from patient
      reported quality of life in ENDEAVOR to estimate quality-adjusted life-years
      (QALYs) from life-years (LYs). RESULTS: The model predicted an average gain of
      1.66 LYs and 1.50 QALYs with Kd56 vs. Vd, and lifetime additional costs of
      $182,699, resulting in an incremental cost-effectiveness ratio (ICER) of
      $121,828/QALY gained. The ICER was $114,793/QALY in patients with 1 prior
      treatment; $99,263/QALY in those not transplanted, and <$150,000/QALY up to an
      85% discount in bortezomib price. CONCLUSIONS: Kd56 is cost-effective for
      patients with R/RMM at a willingness-to-pay threshold of $150,000/QALY. Trial
      data in the model may limit generalizability; however, SEER registry data
      mitigates this challenge. Kd56 provides additional value in key subgroups, and
      remains cost-effective after steep comparator discounts.

PMID- 29027826
TI  - Dietary advanced glycated end-products and medicines influence the expression of
      SIRT1 and DDOST in peripheral mononuclear cells from long-term type 1 diabetes
      patients.
AB  - Quantitative polymerase chain reaction was employed to quantify expression of two
      genes coding for advanced glycation end-product receptors [RAGE ( AGER) and AGER1
      ( DDOST)] and of the gene coding the deacetylase SIRT1 ( SIRT1) in peripheral
      blood mononuclear cells from type 1 diabetes patients without [Group A, n = 35;
      28.5 (24-39) years old; median (interquartile interval)] or with at least one
      microvascular complication [Group B, n = 117; 34.5 (30-42) years old]; 31 healthy
      controls were also included. In a subgroup of 48 patients, daily advanced
      glycation end-products intake before blood collection was assessed. Lower
      expression of DDOST was found in patients than in controls after adjustment for
      sex, age, use of statins, angiotensin-converting enzyme inhibitors and
      angiotensin receptor blockers. Higher expressions of AGER, DDOST and SIRT1 were
      observed in Group A. Stratifying by complications, AGER and DDOST expressions
      were higher in those without retinopathy and without diabetic kidney disease,
      respectively, compared to patients with these complications. Patients using
      statins or angiotensin receptor blockers presented higher expression of DDOST.
      Expression of SIRT1 was higher in patients consuming >=12,872 KU daily of
      advanced glycation end-products. Although AGER, DDOST and SIRT1 are differently
      expressed in peripheral blood mononuclear cells from type 1 diabetes patients
      with and without microvascular complications, they are also influenced by dietary
      advanced glycation end-products and by statins and angiotensin receptor blockers.

PMID- 29027828
TI  - Folate-decorated and NIR-activated nanoparticles based on platinum(IV) prodrugs
      for targeted therapy of ovarian cancer.
AB  - Platinum-based drugs are used to treat a variety of cancers but have many side
      effects such as nephrotoxicity and neurotoxicity. A folate-decorated
      nanoparticles system with a good drug payload can selectively deliver drugs into
      folate receptor (FR)-overexpressing cancer cells to prevent the shortcomings of
      platinum-based chemotherapy. Here, folate-decorated and near-infrared (NIR) laser
      activated nanoparticles (abbreviated as PtIV-FINPs) were prepared via ultrasonic
      self-assembling of platinum(IV) prodrug c,c,t-Pt(NH3)2Cl2(OOCCH2CH2COOH)2, folic
      acid (FA)-functionalized lipid DSPE-PEG-FA and NIR fluorescent dye indocyanine
      green (ICG). The obtained PtIV-FINPs had almost spherical shape with a mean
      diameter about 100 nm. In vitro cellular uptake, cytotoxicity assays revealed
      that upon NIR irradiation, PtIV-FINPs further enhanced cellular uptake and
      generated higher cytotoxicity against human ovarian carcinoma SKOV3 cells than
      non-targeted or non-NIR activated nanoparticles. Thus, the multifunctional
      nanoparticles have potential to be developed as an attractive drug delivery
      system for effective chemotherapy against FR-overexpressing cells.

PMID- 29027827
TI  - Triggering receptor expressed on myeloid cells in the pathogenesis of
      periodontitis: potential novel treatment strategies.
AB  - INTRODUCTION: Periodontal diseases are polymicrobial inflammatory disorders of
      the tissue, ligament, and bone structures supporting teeth. Periodontitis
      (inflammation with corresponding loss of attachment) affects 40-50% of adults.
      Recently, members of the Triggering Receptor on Myeloid Cell (TREM) family have
      been studied to determine their relationship to these diseases. Areas covered:
      TREM-1 is a receptor expressed on the surface of PMNs, monocytes, macrophages,
      dendritic cells, vascular smooth muscle cells, and keratinocytes upregulated in
      the presence of periodontal inflammation. TREM-1 expression can be upregulated by
      oral bacterium Porphyromonas gingivalis that can be abrogated by a sub
      antimicrobial dose of doxycycline. When cleaved from the cell surface, a soluble
      form of TREM-1 (sTREM-1) can be used as a biomarker of inflammation and might
      also provide a link between oral and systemic inflammation. While less
      understood, TREM-2 has a role in osteoclastogenesis which could contribute to the
      alveolar bone destruction seen in more advanced periodontitis. Expert commentary:
      Additional studies to simulate biofilm microenvironment in TREM research are
      warranted. Longitudinal studies determining TREM-1, sTREM-1, and TREM-2 levels in
      tissues over time and progression of periodontal diseases would provide valuable
      information in the role of TREM receptors as indicators of or contributors to the
      disease process.

PMID- 29027829
TI  - Mental health, pain symptoms and systemic comorbidities in women with
      endometriosis: a cross-sectional study.
AB  - INTRODUCTION: Endometriosis is a gynecological disease with a severe impact on
      quality of life. The aim of this study is to assess mental health status in a
      group of women with endometriosis, investigating their clinical history, pain
      symptoms and systemic comorbidities. METHODS: An observational cross-sectional
      study was performed on a group of Italian Caucasian women with endometriosis (n =
      134). All patients filled the 'Patient Health Questionnaire' (PHQ), a self
      administered screening tool for mental health disorders. The characteristics of
      endometriosis, pain symptoms and their severity, the presence and types of
      comorbid systemic disorders were added into the same survey. RESULTS: According
      to PHQ algorithms, 59% of patients were affected by at least one psychiatric
      disorder, with a significant correlation with pain symptoms (p = 0.0026).
      Patients with severe pain showed a higher incidence of multiple psychiatric
      disorders (p = 0.026) and somatoform disorder than those with mild pain (p =
      0.0009). There was no correlation between the presence of psychiatric disorders
      and age, BMI, parity, infertility, need for surgery, number of intervention,
      localization of endometriotic lesions and systemic comorbidities. DISCUSSION:
      Women with endometriosis showed a high frequency of PHQ results positive for
      psychiatric disorders, with a significant association with pain severity.

PMID- 29027830
TI  - Occurrence, types, properties and interactions of phenolic compounds with other
      food constituents in oil-bearing plants.
AB  - Phenolic phytochemicals have become of interest due to their therapeutic
      potential, particularly with regards to their anti-cancer, anti-inflammatory,
      hypolipidemic, and hypoglycemic properties. An evolving area of research
      involving phenolics in foods and their products pertains to the functional,
      biological, and nutritional consequences resulting from the binding between
      certain phenolic compounds and the macronutrient and micronutrient constituents
      of foods. The goal of this review is to provide a summary of studies
      investigating endogenous phenolic interactions with major components in food
      systems, including carbohydrates, proteins, lipids, minerals and vitamins, with a
      focus on the phenolic compounds and nutrients in oil-bearing plants. Another
      major objective is to provide a comprehensive overview of the chemical nature of
      phenolic interactions with food constituents that could affect the quality,
      nutritional and functional properties of foods. Such information can assist in
      the discovery and optimization of specific phenolic complexes in plant-based
      foods that could be utilized towards various applications in the food,
      nutraceutical and pharmaceutical industries.

PMID- 29027831
TI  - Evaluation of brain targeting in rats of Salvianolic acid B nasal delivery by the
      microdialysis technique.
AB  - The purpose of this study was to investigate the biodistribution of Salvianolic
      acid B in rats blood and brain after intranasal administration and explore its
      feasibility and evaluate its brain targeting effect. The concentration of
      Salvianolic acid B in blood and brain following nasal administration (32 mgckg-1)
      was measured combining with microdialysis sampling and liquid chromatograph-mass
      spectrometer/MS detection technology. After the microdialysis samples were
      corrected with in vivo recoveries, the pharmacokinetic parameters were obtained
      by using non-compartment model and the brain targeting evaluated by the value of
      drug targeting index (DTI). The Cmax in blood and brain by intravenous injection
      were higher than intranasal administration, but the intranasal administration of
      MRT0-infinity significantly prolonged and increased by nearly 2.03 and 1.86
      times, respectively. The DTI value of Salvianolic acid B was 5.54 and
      bioavailability (F) was 43.98%. After nasal administration of Salvianolic acid B,
      it has a certain brain targeting, which could become a new drug system for the
      treatment of brain diseases.

PMID- 29027832
TI  - Clinical evaluation of P-glycoprotein inhibition by venetoclax: a drug
      interaction study with digoxin.
AB  - 1. Venetoclax is a novel, small molecule B-cell lymphoma-2 (BCL-2) inhibitor that
      has demonstrated clinical efficacy in a variety of haematological malignancies.
      Since venetoclax is an inhibitor of P glycoprotein (P-gp) transporter, a study
      was conducted in healthy, female volunteers to evaluate the effect of venetoclax
      on the pharmacokinetics of digoxin, a P-gp probe substrate. 2. Volunteers
      received a single oral dose of digoxin (0.5 mg) with or without a single oral
      dose of venetoclax (100  mg). Serial blood samples were obtained for
      pharmacokinetic assessments of digoxin and venetoclax and serial urine samples
      were obtained for measurement of digoxin concentrations. Safety was assessed
      throughout the study. 3. Coadministration of digoxin and venetoclax increased
      digoxin maximum observed plasma concentration (Cmax) by 35% and area under the
      plasma-concentration time curve (AUC0-infinity) by 9%. Digoxin half-life, renal
      clearance and the fraction excreted unchanged in urine remained relatively
      similar. The results of this study indicate that venetoclax can increase the
      concentrations of P-gp substrates. Narrow therapeutic index P-gp substrates
      should be administered six hours prior to venetoclax to minimise the potential
      interaction.

PMID- 29027835
TI  - Identifying the Types of Support Needed by Interprofessional Teams Providing
      Pediatric End-of-Life Care: A Thematic Analysis.
AB  - BACKGROUND: Despite the number of interprofessional team members caring for
      children at the end of life, little evidence exists on how institutions can
      support their staff in providing care in these situations. OBJECTIVE: We sought
      to evaluate which aspects of the hospital work environment were most helpful for
      multidisciplinary team members who care for patients at the end of life and
      identify areas for improvement to better address staff needs. DESIGN: Qualitative
      thematic analysis was completed of free-text comments from a survey distributed
      to interprofessional staff members involved in the care of a recently deceased
      pediatric patient. A total of 2701 surveys were sent; 890 completed. Free-text
      responses were provided by 306 interprofessional team members. SETTING/SUBJECTS:
      Interprofessional team members involved in the care of a child who died at a 348
      bed academic children's hospital in the Midwestern United States. MEASUREMENTS:
      Realist thematic analysis of free-text responses was completed in Dedoose using a
      deductive and inductive approach with line-by-line coding. Descriptive statistics
      of demographic information was completed using Excel. RESULTS: Thematic analysis
      of the 306 free-text responses identified three main support-related themes.
      Interprofessional team members desire to have (1) support through educational
      efforts such as workshops, (2) support from colleagues, and (3) support through
      institutional practices. CONCLUSIONS: Providers who participate in end-of-life
      work benefit from ongoing support through education, interpersonal relationships,
      and institutional practices. Addressing these areas from an interprofessional
      perspective enables staff to provide the optimal care for patients, patients'
      families, and themselves.

PMID- 29027834
TI  - Extrapolation of plasma clearance to understand species differences in
      toxicokinetics of bisphenol A.
AB  - 1. Understanding species differences in the toxicokinetics of bisphenol A (BPA)
      is central to setting acceptable exposure limits for human exposures to BPA. BPA
      toxicokinetics have been well studied, with controlled oral dosing studies in
      several species and across a wide dose range. 2. We analyzed the available
      toxicokinetic data for BPA following oral dosing to assess potential species
      differences and dose dependencies. BPA is rapidly conjugated and detoxified in
      all species. The toxicokinetics of BPA can be well described using non
      compartmental analyses. 3. Several studies measured free (unconjugated) BPA in
      blood and reported area under the curve (AUC) of free BPA in blood of mice, rats,
      monkeys, chimpanzees and humans following controlled oral doses. Extrinsic
      clearance was calculated and analyzed across species and dose using allometric
      scaling. 4. The results indicate free BPA clearance is well described using
      allometric scaling with high correlation coefficients across all species and
      doses up to 10 mg/kg. The results indicate a human equivalent dose factor (HEDf)
      of 0.9 is appropriate for extrapolating a point of departure from mice and rats
      to a human equivalent dose (HED), thereby replacing default uncertainty factors
      for animal to human toxicokinetics.

PMID- 29027833
TI  - Trichostatin A and 5-Aza-2'-Deoxycytidine influence the expression of cold
      induced genes in Arabidopsis.
AB  - The expression of cold-induced genes is critical for plants to survive under
      freezing stress. However, the underlying mechanisms for the decision of when,
      where, and which genes to express are unclear when a plant meets a sudden
      temperature drop. Previous studies have demonstrated epigenetics to play a
      central role in the regulation of gene expression in plant responses to
      environmental stress. DNA methylation and histone deacetylation are the two most
      important epigenetic modifications. This study was conducted to investigate the
      effects of inhibiting DNA methylation and histone deacetylation on gene
      expression, and to explore the potential role of epigenetics in plant responses
      to cold stress. The results revealed that histone deacetylase inhibitors
      (trichostatin A) and DNA methylation inhibitors (5-Aza-2'-deoxycytosine)
      treatment enhanced cold tolerance. DNA microarray analysis and the gene ontology
      method revealed 76 cold-induced differently expressed genes in Arabidopsis
      thaliana seedlings that were treated to 0 degrees C for 24 h following
      Trichostatin A and 5-Aza-2'-Deoxycytidine. Furthermore, analyses of metabolic
      pathways and transcription factors of 3305 differentially expressed genes were
      performed. Each four metabolic pathways were significantly affected (p < 0.01) by
      Trichostatin A and 5-Aza-2'-Deoxycytidine. Finally, 10 genes were randomly
      selected and verified via qPCR analysis. Our study indicated that Trichostatin A
      and 5-Aza-2'-Deoxycytidine can improve the plant cold resistance and influence
      the expression of the cold-induced gene in A. thaliana. This result will advance
      our understanding of plant freezing responses and may provide a helpful strategy
      for cold tolerance improvement in crops.

PMID- 29027836
TI  - Developing Macroindicators of Palliative Care Development in Africa: A Process
      with In-Country and International Experts.
AB  - BACKGROUND: Indicators specific to the African context are important to measure
      palliative care (PC) development accurately. OBJECTIVE: To describe the process
      used to develop a set of PC macroindicators for Africa. DESIGN: Open-ended
      interviews on national PC development were conducted with five African Country
      Experts. Indicators were rated (1-4) by 14 Country Experts for validity and
      feasibility. An additional 11 interviews were conducted to ensure indicator
      saturation. Indicators scoring >=3 proceeded to a modified two-round RAND/UCLA
      Delphi with global experts on PC development (International Committee). Finally,
      indicators were ranked by the project team. SETTING/SUBJECTS: Sixteen country
      experts from 7 African countries and 14 International Committee members. RESULTS:
      One hundred three indicators were rated by Country Experts, and 58 proceeded to
      the Delphi. Thirty-eight indicators were rated as important by the International
      Committee, and the project team ranked 19 of these as most important. Service
      indicators (n = 6) included the number of types of services most important in
      Africa (e.g., hospices, home based) and coverage. Policy indicators (n = 4)
      included the existence of PC in national policies, guidelines, and budget and a
      responsible person. Education indicators (n = 3) consisted of inclusion of PC in
      medical and nursing curricula and recognition as a specialty. Medicine indicators
      (n = 4) focused on morphine availability, consumption, and prescribing barriers.
      Vitality indicators (n = 2) reflected the existence of a national association and
      its activity. CONCLUSION: The process to develop African-specific PC indicators
      resulted in 19 indicators that were used to measure PC development as a
      comparative baseline for development in African countries.

PMID- 29027838
TI  - The role of appraisal in dysphoric affect reactivity to positive laboratory films
      and daily life events in depression.
AB  - Hedonic deficits are linked to protracted dysphoric affect (DA) in depression, a
      disorder characterised by emotion context insensitivity (ECI). Recent findings
      from daily life studies contradict the ECI view. This study longitudinally
      investigated DA across laboratory and daily life contexts and the conditions
      associated with discrepancies in DA reactivity. Thirty-three healthy controls and
      41 adults with major depressive disorder (MDD) provided responses to neutral and
      positive (a) films viewed in the laboratory and (b) daily events recorded over
      the course of three days using ecological momentary assessment (EMA) methodology.
      The current study reports on participants' appraisals of films and events and
      their subsequent DA, both rated individually after each task and daily event.
      Despite large group similarities in appraisals of the positive film and life
      events, MDDs appraised the neutral film and neutral life events as less important
      (film: d = .58; event: eta2 = .07) and less pleasant (film: d = .56; event: eta2
      = .18) relative to controls. While MDDs reported higher DA both in the laboratory
      and in daily life, they experienced larger decreases in DA during positive life
      events (B = -.77, SE = .28, t(73) = -2.70, p = .009), but not in response to the
      positive film relative to controls. Results indicate that higher pleasantness
      appraisals in daily life predicted larger decreases in DA among MDDs than
      controls (B = -.24, SE = .06, t(73) = -4.10, p < .001). Finally, lower
      pleasantness appraisals of a standardised neutral film predicted larger DA
      decreases among MDDs during positive life events (B = 1.28, SE = .46, t(73) =
      2.77, p = .006). The implications of valence and relevance of context for DA
      reactivity and mood repair are discussed.

PMID- 29027837
TI  - Malpractice in paediatric minimally invasive surgery - a current concept: Results
      of an international survey.
AB  - This study aimed to assess malpractice in paediatric minimally invasive surgery
      (MIS), and attitudes, prevention strategies and mechanisms to support surgeons
      while they are under investigation. An observational, multicentric, questionnaire
      based study was conducted. The survey questionnaire was sent via mail, and it
      comprised four sections. Twenty-four paediatric surgeons (average age 54.6
      years), from 13 different countries, participated in this study. The majority had
      >15 years of experience in MIS. Three (12.5%) surgeons reported a total of five
      malpractice claims regarding their MIS activity. The reasons for the claims were
      a postoperative complication in 3/5 (60%) cases, a delayed/failed diagnosis in
      1/5 (20%) cases and the death of the patient in 1/5 (20%) cases. The claims
      concluded with the absolution of the surgeon in all cases, and monetary
      compensation to the claimant in two (40%) cases. Eleven (45.8%) surgeons were
      invited as expert counsels in medico-legal actions. Medico-legal aspects have a
      minimal impact on the MIS activity of paediatric surgeons. In this series, claims
      concluded with the absolution of the surgeon in all cases, but they had a
      negative effect on the surgeon's reputation and finances. A key element in
      supporting surgeons while they are under investigation is always to choose a
      surgeon who is an expert in paediatric MIS as legal counsel. A constant update on
      innovations in paediatric MIS and appropriate professional liability insurance
      may also play a key role in reducing medico-legal consequences.

PMID- 29027839
TI  - EphB receptors, mainly EphB3, contribute to the proper development of cortical
      thymic epithelial cells.
AB  - EphB and their ligands ephrin-B are an important family of protein tyrosine
      kinase receptors involved in thymocyte-thymic epithelial cell interactions known
      to be key for the maturation of both thymic cell components. In the present
      study, we have analyzed the maturation of cortical thymic epithelium in EphB
      deficient thymuses evaluating the relative relevance of EphB2 and EphB3 in the
      process. Results support a relationship between the epithelial hypocellularity of
      mutant thymuses and altered development of thymocytes, lower proportions of
      cycling thymic epithelial cells and increased epithelial cell apoptosis.
      Together, these factors induce delayed development of mutant cortical TECs,
      defined by the expression of different cell markers, i.e. Ly51, CD205, MHCII,
      CD40 and beta5t. Furthermore, although both EphB2 and EphB3 are necessary for
      cortical thymic epithelial maturation, the relevance of EphB3 is greater since
      EphB3-/- thymic cortex exhibits a more severe phenotype than that of EphB2
      deficient thymuses.

PMID- 29027840
TI  - Male factor infertility and risk of multiple sclerosis: A register-based cohort
      study.
AB  - BACKGROUND: Gender, possibly due to the influence of gonadal hormones, is
      presumed to play a role in the pathogenesis of multiple sclerosis (MS), but no
      studies have evaluated whether male infertility is associated with MS. OBJECTIVE:
      To study the association between male factor infertility and prevalent as well as
      incident MS. METHOD: Our cohort was established by linkage of the Danish National
      in vitro fertilization (IVF) registry to The Danish Multiple Sclerosis Registry
      and consisted of 51,063 men whose partners had undergone fertility treatment in
      all public and private fertility clinics in Denmark between 1994 and 2015.
      RESULTS: With a median age of 34 years at baseline, 24,011 men were diagnosed
      with male factor infertility and 27,052 did not have male factor infertility and
      made up the reference group. Men diagnosed with male factor infertility had a
      higher risk of prevalent (odds ratio (OR) = 1.61, 95% confidence interval (95%
      CI) 1.04-2.51) and incident MS (hazard ratio (HR) = 1.28, 95% CI 0.76-2.17) when
      compared to the reference group. CONCLUSION: This nationwide cohort study has
      shown, for the first time, an association between male infertility and MS which
      may be due to underlying common etiologies such as hypogonadism, shared genetics,
      or a joint autoimmune component.

PMID- 29027841
TI  - Diffusion tensor tractography in cerebral small vessel disease: correlation with
      cognitive function.
AB  - Background Patients with cerebral small vessel disease may suffer from varying
      levels of cognitive deficit and may progress on to vascular dementia. The extent
      of involvement, as seen on conventional magnetic resonance (MR) measures,
      correlates poorly with the level of cognitive decline. The purpose of this study
      was to investigate the utility of diffusion tensor imaging (DTI) as a marker for
      white matter damage in small vessel disease and to assess its correlation with
      cognitive function. Methods Thirty consecutive patients with cerebral small
      vessel disease underwent conventional MR imaging, DTI, and neuropsychological
      assessment. Results On tractographic analysis, fractional anisotropy was
      significantly reduced while mean diffusivity significantly increased in several
      white matter tracts. The alteration in DTI indices correlated well with cognitive
      function. No significant correlation was identified between T2 lesion load and
      cognitive performance. Conclusions Tractographic analysis of white matter
      integrity is a useful measure of disease severity and correlates well with
      cognitive function. It may have a significant potential in monitoring disease
      progression and may serve as a surrogate marker for treatment trials.

PMID- 29027843
TI  - The impact of vascular risk factors on brain volume and lesion load in patients
      with early multiple sclerosis.
AB  - BACKGROUND: Vascular risk factors (VRF) in multiple sclerosis (MS) patients have
      been associated with lower brain volumes. It is currently unknown if this
      association already exists in early MS and how it develops over time. METHODS: We
      identified 82 patients with clinically isolated syndrome (CIS) ( n = 61) or with
      early relapsing-remitting MS ( n = 21) and assessed their VRF including arterial
      hypertension, hyperlipidaemia, diabetes mellitus and smoking. We analysed T2
      lesion load, normalized brain volume (NBV), cortical grey (cGMV) and white matter
      volumes (WMV), thalamic and basal ganglia volumes at baseline and follow-up
      magnetic resonance imaging (MRI) and assessed the percentage of brain volume
      change (PBVC) using SIENA. RESULTS: Patient mean age was 32.4 (+/-8.7) years and
      54 (65%) were women. Median follow-up period was 42 (29-54) months. In total, 26
      patients (31.7%) had one or more VRF (VRF+). At baseline, VRF+ patients had a
      lower NBV (1530.9 cm3 vs 1591.2 cm3, p = 0.001), a lower cGMV (628.5 cm3 vs 668.6
      cm3, p = 0.002) and WMV (752.2 cm3 vs 783.9 cm3, p = 0.009) than VRF-negative
      patients. Similar results were obtained at follow-up. PBVC was comparable between
      patients with and without VRF. CONCLUSION: VRF are associated with lower brain
      volume already in early MS but do not lead to increased brain volume loss during
      3.5 years of follow-up.

PMID- 29027842
TI  - WRKY transcription factors are involved in brassinosteroid signaling and mediate
      the crosstalk between plant growth and drought tolerance.
AB  - Brassinosteroids (BRs) are critical for the plant growth and development. BRs
      signal through the plasma membrane localized receptor-like kinases to downstream
      transcription factors BES1/BZR1 to regulate the expression of thousands of genes
      for various BR responses. In addition to the role in plant growth and
      development, BRs have been implicated in responses to environmental stresses such
      as drought. However, the mechanism through which BRs regulate drought have just
      begun emerging. We have recently found that a group of WRKY transcription
      factors, WRKY46, WRKY54, WRKY70, which are well known for the function in abiotic
      and biotic stress, cooperates with BES1 to mediate BR-regulated drought response.
      The wrky46 wrky54 wrky70 triple mutants showed growth defect, likely due to
      impaired BR signaling as well as some reduction of endogenous BR level.
      WRKY46/54/70 cooperates with BES1 to regulate the expression of BR target genes
      to promote growth. We also found that WRKY46/54/70 negatively modulates drought
      tolerance by globally repressing drought-inducible gene expression. Thus, our
      result uncovers a new role for WRKY transcription factors in BR signaling and
      provides the molecular mechanism for BR-regulated plant growth and drought stress
      through WRKY46/54/70 and BES1 transcription factors.

PMID- 29027844
TI  - Controversies and best practices for acute scaphoid fracture management.
AB  - Acute scaphoid fractures are common wrist injuries that continue to elicit debate
      from surgeons regarding the most appropriate diagnostic and management
      algorithms. This review will examine the current literature and trends, in an
      attempt to provide the reader with an evidence-based discussion regarding current
      controversies of interest to clinicians. In addition, an attempt will be made to
      provide recommendations for the best treatment practices for acute scaphoid
      fractures.

PMID- 29027846
TI  - Letters to the Editor.

PMID- 29027845
TI  - The potent mechanism-based inactivation of CYP2D6 and CYP3A4 with fusidic acid in
      in vivo bioaccumulation.
AB  - 1. The accumulation of fusidic acid (FA) after multiple doses of FA has been
      reported on in previous studies but the related mechanisms have not been
      clarified fully. In the present study, we explain the mechanisms related to the
      mechanism-based inactivation of CYP2D6 and CYP3A4. 2. The irreversible inhibitory
      effects of FA on CYP2D6 and CYP3A4 were examined via a series of experiments,
      including: (a) time-, concentration- and NADPH-dependent inactivation, (b)
      substrate protection in enzyme inactivation and (c) partition ratio with
      recombinant human CYP enzymes. Metoprolol alpha-hydroxylation and midazolam 1'
      hydroxylation were used as marker reactions for CYP2D6 and CYP3A4 activities, and
      HPLC-MS/MS measurement was also utilised. 3. FA caused to the time- and
      concentration-dependent inactivation of CYP2D6 and CYP3A4. About 55.8% of the
      activity of CYP2D6 and 75.8% of the activity of CYP3A4 were suppressed after
      incubation with 10 MUM FA for 15 min. KI and kinact were found to be 2.87 MUM and
      0.033 min-1, respectively, for CYP2D6, while they were 1.95 MUM and 0.029 min-1,
      respectively, for CYP3A4. Inhibition of CYP2D6 and CYP3A4 activity was found to
      require the presence of NADPH. Substrates of CYP2D6 and CYP3A4 showed that the
      enzymes were protected against the inactivation induced by FA. The estimated
      partition ratio for the inactivation was 7 for CYP2D6 and 12 for CYP3A4. 4. FA is
      a potent mechanism-based inhibitor of CYP2D6 and CYP3A4, which may explain the
      accumulation of FA in vivo.

PMID- 29027847
TI  - Antimicrobial activity of a bioelectric dressing using an in vitro wound pathogen
      colony drip-flow reactor biofilm model.
AB  - OBJECTIVE: We performed in vitro antibiofilm testing of a silver and zinc
      containing microcurrent generating bioelectric dressing (BED) against clinical
      wound pathogens to determine its efficacy in preventing biofilm formation under
      low shear and continuous flow conditions, simulating wound infection
      environments. METHOD: We customised an in vitro colony drip-flow reactor (DFR)
      biofilm model for efficacy evaluation of BED. Each bacterial pathogen was diluted
      to 104CFU/ml and inoculated on the polycarbonate filter membrane as an abiotic
      support. BED and controls (no treatment, gauze, and blank polyester with no
      silver and zinc) were applied directly on the membranes where bacterial cultures
      were inoculated. Biofilms were continuously developed onto the membranes for 72
      hours at room temperature. Biofilm formation was confirmed by crystal violet
      staining and microscopic observation. Through vigorous shaking and sonication,
      the released bacteria were serially diluted, plated, and incubated for 24 hours
      at 37 degrees C to determine the numbers of surviving bacteria. RESULTS: Biofilms
      were well developed onto blank polyesters, but not the BED after 72 hours
      incubation. Crystal violet staining from the blank polyesters showed large and
      fully grown biofilms. We observed an inhibition in bacterial growth on BED
      treatment. The antibiofilm activity of the BED against each of eight monospecies
      biofilms showed a 1- or 2 log10 (or 10- or 100-fold) reduction in bacterial
      numbers compared with those of controls. CONCLUSION: Our results demonstrated
      that colony DFR biofilm model was an appropriate for testing the antibiofilm
      efficacy of BED under low shear and continuous flow conditions for simulating
      clinical wound environments. The bioelectric currents generated from the silver
      and zinc active ingredients in the dressing resulted in antibiofilm activity of
      this wound care device. DECLARATION OF INTEREST: The opinions or assertions
      contained herein are the private views of the authors, based on scientific
      investigation, and are not to be construed as official or as reflecting the views
      of the Department of Defense, the United States Government or any of the authors'
      employers. Dr. Mina Izadjoo has served as a consultant to Vomaris Innovations
      Inc.

PMID- 29027848
TI  - Evaluation of tissue engineering products for the management of neuropathic
      diabetic foot ulcers: an interim analysis.
AB  - OBJECTIVE: The objective of this prospective, multicentre clinical study is to
      assess the application of MatriStem MicroMatrix (MSMM) and MatriStem Wound Matrix
      (MSWM) (porcine urinary bladder derived extracellular matrix) compared with
      Dermagraft (DG) (human fibroblast-derived dermal substitute) for the management
      of non-healing diabetic foot ulcers (DFUs). METHOD: A randomised, multicentre
      study was conducted at thirteen centers throughout the US. It was designed to
      evaluate the incidence of ulcer closure, rate of ulcer healing, wound
      characteristics, patient quality of life, cost-effectiveness, and recurrence.
      Those subjects whose DFUs decreased in size by <=30% or increased by <=50% during
      the standard of care (SOC) phase were randomised into the treatment phase of the
      study. The study evaluated complete wound closure by eight weeks with weekly
      device application. A two-week post treatment SOC phase followed the treatment
      phase for any wounds that did not heal by the end of eight weeks, and wound
      closure was also evaluated at the end of that period. Ulcer recurrence at 6
      months post-treatment was evaluated in the subjects that showed wound healing by
      the end of the post-treatment SOC phase. Standard adjunctive therapy, including
      debridement, saline irrigation and foot off-loading, was provided to both arms
      during the four-week screening period, after which eligible subjects were
      randomised in a 1:1 ratio, to either the MatriStem (MS) or DG treatment arm. This
      study was developed to evaluate the hypothesis that the wound outcomes observed
      after wound management with MS were non-inferior to those of DG after eight
      weeks. The authors present the planned interim results of this study after one
      half of the projected enrolment was completed. RESULTS: There were 95 subjects
      consented and entered into the SOC four-week screening phase of the trial and 56
      were randomised into the treatment phase. At the planned interim analysis, there
      was a significantly lower cost per subject and significant improvement in patient
      quality of life for the subjects treated with MS compared with those managed with
      DG. However, there was not a statistically significant difference found during
      the analysis of the interim data between the two study groups for rate of wound
      healing or number of subjects with complete wound closure. CONCLUSION: The data
      from this interim analysis show that MSMM and MSWM provide results for healing
      DFUs that are similar to the results obtained for DG at a significant quality of
      life and economic advantage. DECLARATION OF INTEREST: The opinions expressed are
      those of the authors and not necessarily those of the Department of Veterans
      Affairs or the United States Government. T.W. Gilbert is employed as the Chief
      Science Officer and is a stockholder in ACell, Inc., which commercializes
      MatriStem Wound Matrix and MicroMatrix. None of the other authors have a conflict
      of interest to declare.

PMID- 29027849
TI  - Immune and vascular dysfunction in diabetic wound healing.
AB  - : The diminished capacity for wound healing in patients with diabetes contributes
      to morbidity through ulceration and recurrent infections, loss of function and
      decreased workplace productivity, increased hospitalisation rates, and rising
      health-care costs. These are due to diabetes' effects on signalling molecules,
      cellular cascades, different cell populations, and the vasculature. The function
      of multiple immune system components including cellular response, blood factors,
      and vascular tone are all negatively impacted by diabetes. The purpose of this
      paper is to review the current understanding of immune and vascular dysfunction
      contributing to impaired wound healing mechanisms in the diabetic population.
      Normal wound healing mechanisms are reviewed followed by diabetic aberrations to
      immune and inflammatory function and atherogenesis and angiopathy. DECLARATION OF
      INTEREST: The authors have no financial or personal relationships to people or
      organisations that could potentially and inappropriately influence their work and
      conclusions.

PMID- 29027851
TI  - Treatment of diabetic foot ulcers with dehydrated amniotic membrane allograft: a
      prospective case series.
AB  - OBJECTIVE: A diabetic foot ulcer (DFU) is one of the many potential complications
      associated with diabetes. If not effectively and rapidly treated, DFUs can result
      in lower extremity amputations. This prospective case series aimed to assess the
      effectiveness of a dehydrated amniotic-derived tissue allograft (DAMA), with
      regards to time to wound closure and total number of applications. METHOD:
      Patients were recruited with a neuropathic non-healing DFU(s) despite standard
      care for at least 4 weeks before the study. The number of DAMA applications and
      time between applications was based on the physician's judgment. For the majority
      of patients (n=13/14), offloading, usually total contact casting (TCC), was used
      in conjunction with DAMA. Wounds were assessed, measured, and photographed every
      1-2 weeks. RESULTS: Cases included 14 patients (11 men, 3 women; mean age 56.7+/
      9.1 years) with 15 non-healing neuropathic DFUs with a mean baseline wound area
      of 6.5+/-11.6cm2 (median: 2.2cm2; range: 0.1-44.2cm2) and mean volume of 4.3+/
      10.9cm3 (median: 0.3cm3; range: 0-39.8cm3). All patients in this series achieved
      complete wound closure within a median time of 5 weeks (range: 1-14 weeks). Wound
      area was reduced by a median of 58.3% at week 1 and 74.1% at week 3, and volume
      by a median of 62.8% at week 1, 97.4% at week 3 and by a median of 100% at week 5
      and all time points thereafter. Patients received a median of 2 DAMA applications
      (range: 1-11). In those that required more than 1 application (n=12), DAMA was
      applied at intervals of 1 week (n=3) or >=2 weeks (n=9). Smaller wounds (areas
      <2.2cm2) closed rapidly (<1 month, 1-2 applications), whereas larger wounds
      (>2.2cm2) required >2 weekly/biweekly applications. CONCLUSION: The use of DAMA,
      particularly when coupled with TCC, led to wound closure of DFUs in all patients
      in this case series, including complex patients with DFUs of >=1 year in
      duration, lack of prior response to conservative treatment measures, area >10cm2
      and/or multiple comorbidities. Prospective randomised trials would help to
      elucidate the precise role of DAMA in these encouraging results. DECLARATION OF
      INTEREST: Derma Sciences, Inc. (Princeton, NJ) funded editorial support services.

PMID- 29027852
TI  - A single-centre, retrospective study of cryopreserved umbilical cord/amniotic
      membrane tissue for the treatment of diabetic foot ulcers.
AB  - OBJECTIVE: Histopathological studies have shown a prolonged inflammatory phase in
      wounds of patients with diabetes, delaying formation of mature granulation tissue
      and reducing wound tensile strength, making these wounds difficult for physicians
      to heal. Cryopreserved human umbilical cord (cUC) tissues possess unique anti
      inflammatory and anti-scarring properties and have been found to help improve
      closure of these chronic wounds. METHOD: A retrospective chart review was
      performed to assess the efficacy of cUC as an advanced treatment modality to help
      promote the closure of chronic DFUs. Overall healing rate, duration to wound
      closure, and number of cUC applications used to achieve closure were used to
      assess cUC treatment efficacy. RESULTS: A total of 32 wounds in 29 patients
      treated at a single health-care centre were included in the study population The
      average initial wound area for all wounds was 10.6 +/- 2.15cm2. Of the 32 wounds
      28 achieved complete epithelialisation for an overall healing rate of 87.5%.
      Average time to wound closure was 13.8 +/- 1.95 weeks with a median of 9 weeks
      and an average of 1.68 +/- 0.18 cUC applications. CONCLUSION: The results suggest
      cUC allograft may be effective in improving the healing of DFUs ulcers as well as
      potentially reducing the medical costs associated with chronic DFUs due to the
      low number of applications needed to achieve complete wound closure. Prospective,
      randomised controlled trials are suggested to better understand the efficacy of
      cUC in chronic wound healing. DECLARATION OF INTEREST: Dr Raphael is a paid
      speaker for Amniox Medical, Inc.

PMID- 29027853
TI  - Intraoperative test stimulation versus stereotactic accuracy as a surgical end
      point: a comparison of essential tremor outcomes after ventral intermediate
      nucleus deep brain stimulation.
AB  - OBJECTIVE Ventral intermediate nucleus deep brain stimulation (DBS) for essential
      tremor is traditionally performed with intraoperative test stimulation and
      conscious sedation, without general anesthesia (GA). Recently, the authors
      reported retrospective data on 17 patients undergoing DBS after induction of GA
      with standardized anatomical coordinates on T1-weighted MRI sequences used for
      indirect targeting. Here, they compare prospectively collected data from
      essential tremor patients undergoing DBS both with GA and without GA (non-GA).
      METHODS Clinical outcomes were prospectively collected at baseline and 3-month
      follow-up for patients undergoing DBS surgery performed by a single surgeon.
      Stereotactic, euclidean, and radial errors of lead placement were calculated.
      Functional (activities of daily living), quality of life (Quality of Life in
      Essential Tremor [QUEST] questionnaire), and tremor severity outcomes were
      compared between groups. RESULTS Fifty-six patients underwent surgery: 16 without
      GA (24 electrodes) and 40 with GA (66 electrodes). The mean baseline functional
      scores and QUEST summary indices were not different between groups (p = 0.91 and
      p = 0.59, respectively). Non-GA and GA groups did not differ significantly
      regarding mean postoperative percentages of functional improvement (non-GA, 47.9%
      vs GA, 48.1%; p = 0.96) or QUEST summary indices (non-GA, 79.9% vs GA, 74.8%; p =
      0.50). Accuracy was comparable between groups (mean radial error 0.9 +/- 0.3 mm
      for non-GA and 0.9 +/- 0.4 mm for GA patients) (p = 0.75). The mean euclidean
      error was also similar between groups (non-GA, 1.1 +/- 0.6 mm vs GA, 1.2 +/- 0.5
      mm; p = 0.92). No patient had an intraoperative complication, and the number of
      postoperative complications was not different between groups (non-GA, n = 1 vs
      GA, n = 10; p = 0.16). CONCLUSIONS DBS performed with the patient under GA to
      treat essential tremor is as safe and effective as traditional DBS surgery with
      intraoperative test stimulation while the patient is under conscious sedation
      without GA.

PMID- 29027854
TI  - Long-term outcomes of tissue-based ACTH-antibody assay-guided transsphenoidal
      resection of pituitary adenomas in Cushing disease.
AB  - OBJECTIVE Cushing disease is caused by a pituitary micro- or macroadenoma that
      hypersecretes adrenocorticotropic hormone (ACTH), resulting in hypercortisolemia.
      For decades, transsphenoidal resection (TSR) has been an efficacious treatment
      but with certain limitations, namely precise tumor localization and complete
      excision. The authors evaluated the novel use of a double-antibody sandwich assay
      for the real-time quantitation of ACTH in resected pituitary specimens with the
      goals of augmenting pathological diagnosis and ultimately improving long-term
      patient outcome. METHODS This study involved a retrospective review of records
      and an analysis of assay values, pathology slides, and MRI studies of patients
      with Cushing disease who had undergone TSR in the period from 2009 to 2014 and
      had at least 1 year of follow-up in coordination with an endocrinologist. In the
      operating room, biopsy specimens from the patients had been analyzed for tissue
      ACTH concentration. Additional samples were simultaneously sent for frozen
      section pathological analysis. The ACTH assay performance was compared against
      pathology assessments of surgical tumor samples using receiver operating
      characteristic (ROC) analysis and against pre- and postoperative MRI studies.
      RESULTS Fourteen patients underwent TSR with guidance by ACTH-antibody assay and
      pathological assessment of 127 biopsy samples and were followed up for an average
      of 3 years. The ACTH threshold for discriminating adenomatous from normal tissue
      was 290,000 pg/mg of tissue, based on jointly maximized sensitivity (95.0%) and
      specificity (71.3%). Lateralization discordance between preoperative MRI studies
      and surgical visualization was noted in 3 patients, confirming the impression
      that MRI alone may not achieve optimal localization. A majority of the patients
      (85.7%) attained long-term disease remission based on urinary free cortisol
      levels, plasma cortisol levels, and long-term corticosteroid therapy. Comparisons
      of patient-months of remission and treatment failure showed that the remission
      rate in the study sample statistically exceeds the rate in historical controls
      (71.9%; p = 0.0007, Fisher's exact test). Long-term unexpected hormonal
      deficiencies were statistically similar between study patients (29%) and those in
      a meta-analysis (25%; p = 0.7596, Fisher's exact test). CONCLUSIONS These
      preliminary findings reflect the promising potential of tissue-based ACTH
      antibody-guided assay for improving the cure rates of Cushing disease patients
      undergoing TSR. Further studies with larger sample sizes, further refinements of
      assay interpretation, and longer-term follow-ups are needed.

PMID- 29027855
TI  - Mesial temporal lobe epilepsy: long-term seizure outcome of patients primarily
      treated with transsylvian selective amygdalohippocampectomy.
AB  - OBJECTIVE The aim of this study was to present long-term seizure outcome data in
      a consecutive series of patients with refractory mesial temporal lobe epilepsy
      primarily treated with transsylvian selective amygdalohippocampectomy (SAHE).
      METHODS The authors retrospectively analyzed prospectively collected data for all
      patients who had undergone resective surgery for medically refractory epilepsy at
      their institution between July 1994 and December 2014. Seizure outcome was
      assessed according to the International League Against Epilepsy (ILAE) and the
      Engel classifications. RESULTS The authors performed an SAHE in 158 patients (78
      males, 80 females; 73 right side, 85 left side) with a mean age of 37.1 +/- 10.0
      years at surgery. Four patients lost to follow-up and 1 patient who committed
      suicide were excluded from analysis. The mean follow-up period was 9.7 years. At
      the last available follow-up (or before reoperation), 68 patients (44.4%) had
      achieved an outcome classified as ILAE Class 1a, 46 patients (30.1%) Class 1, 6
      patients (3.9%) Class 2, 16 patients (10.4%) Class 3, 15 patients (9.8%) Class 4,
      and 2 patients (1.3%) Class 5. These outcomes correspond to Engel Class I in
      78.4% of the patients, Engel Class II in 10.5%, Engel Class III in 8.5%, and
      Engel Class IV in 2.0%. Eleven patients underwent a second surgery (anterior
      temporal lobectomy) after a mean of 4.4 years from the SAHE (left side in 6
      patients, right side in 5). Eight (72.7%) of these 11 patients achieved seizure
      freedom. The overall ILEA seizure outcome since (re)operation after a mean follow
      up of 10.0 years was Class 1a in 72 patients (47.0%), Class 1 in 50 patients
      (32.6%), Class 2 in 7 patients (4.6%), Class 3 in 15 patients (9.8%), Class 4 in
      8 patients (5.2%), and Class 5 in 1 patient (0.6%). These outcomes correspond to
      an Engel Class I outcome in 84.3% of the patients. CONCLUSIONS A satisfactory
      long-term seizure outcome following transsylvian SAHE was demonstrated in a
      selected group of patients with refractory temporal lobe epilepsy.

PMID- 29027856
TI  - Obituary. Robert H. Wilkins, MD, 1934-2017.

PMID- 29027857
TI  - Is there added value in obtaining cervical spine MRI in the assessment of
      nontraumatic angiographically negative subarachnoid hemorrhage? A retrospective
      study and meta-analysis of the literature.
AB  - OBJECTIVE Diagnostic algorithms for nontraumatic angiographically negative
      subarachnoid hemorrhage (AN-SAH) vary, and the optimal method remains subject to
      debate. This study assessed the added value of cervical spine MRI in identifying
      a cause for nontraumatic AN-SAH. METHODS Consecutive patients 18 years of age or
      older who presented with nontraumatic SAH between February 1, 2009, and October
      31, 2014, with negative cerebrovascular catheter angiography and subsequent
      cervical MRI were studied. Patients with intraparenchymal, subdural, or epidural
      hemorrhage; recent trauma; or known vascular malformations were excluded. All
      cervical MR images were reviewed by two blinded neuroradiologists. The diagnostic
      yield of cervical MRI was calculated. A literature review was conducted to
      identify studies reporting the diagnostic yield of cervical MRI in patients with
      AN-SAH. The weighted pooled estimate of diagnostic yield of cervical MRI was
      calculated. RESULTS For all 240 patients (mean age 53 years, 48% male), catheter
      angiography was performed within 4 days after admission (median 12 hours,
      interquartile range [IQR] 10 hours). Cervical MRI was performed within 19 days of
      admission (median 24 hours, IQR 10 hours). In a single patient, cervical MRI
      identified a source for SAH (cervical vascular malformation). Meta-analysis of 7
      studies comprising 538 patients with AN-SAH produced a pooled estimate of 1.3%
      (95% confidence interval 0.5%-2.5%) for diagnostic yield of cervical MRI. No
      statistically significant between-study heterogeneity or publication bias was
      identified. CONCLUSIONS Cervical MRI following AN-SAH, in the absence of findings
      to suggest spinal etiology, has a very low diagnostic yield and is not routinely
      necessary.

PMID- 29027858
TI  - Role of the temporal pole in temporal lobe epilepsy seizure networks: an
      intracranial electrode investigation.
AB  - OBJECTIVE A convergence of clinical research suggests that the temporal pole (TP)
      plays an important and potentially underappreciated role in the genesis and
      propagation of seizures in temporal lobe epilepsy (TLE). Understanding its role
      is becoming increasingly important because selective resections for medically
      intractable TLE spare temporopolar cortex (TPC). The purpose of this study was to
      characterize the role of the TPC in TLE after using dense electrocorticography
      (ECoG) recordings in patients undergoing invasive monitoring for medically
      intractable TLE. METHODS Chronic ECoG recordings were obtained in 10 consecutive
      patients by using an array customized to provide dense coverage of the TP as part
      of invasive monitoring to localize the epileptogenic zone. All patients would
      eventually undergo cortico-amygdalohippocampectomy. A retrospective review of the
      patient clinical records including ECoG recordings, neuroimaging studies,
      neuropathology reports, and clinical outcomes was performed. RESULTS In 7
      patients (70%), the TP was involved at seizure onset; in 7 patients (70%), there
      were interictal discharges from the TP; and in 1 case, there was early spread to
      the TP. Seizure onset in the TP did not necessarily correlate with preoperative
      neuroimaging abnormalities of the TP. CONCLUSIONS These data demonstrate that TPC
      commonly plays a crucial role in temporal lobe seizure networks. Seizure onset
      from the TP would not have been predicted based on available neuroimaging data or
      interictal discharges. These findings illustrate the importance of thoroughly
      considering the role of the TP prior to resective surgery for TLE, particularly
      when selective mesial resection is being considered.

PMID- 29027860
TI  - Editorial. Refining manuscript elements in the Journal of Neurosurgery: when less
      is more.

PMID- 29027859
TI  - Quantitative cerebral blood flow using xenon-enhanced CT after decompressive
      craniectomy in traumatic brain injury.
AB  - OBJECTIVE Few studies have reported on changes in quantitative cerebral blood
      flow (CBF) after decompressive craniectomy and the impact of these measures on
      clinical outcome. The aim of the present study was to evaluate global and
      regional CBF patterns in relation to cerebral hemodynamic parameters in patients
      after decompressive craniectomy for traumatic brain injury (TBI). METHODS The
      authors studied clinical and imaging data of patients who underwent xenon
      enhanced CT (XeCT) CBF studies after decompressive craniectomy for evacuation of
      a mass lesion and/or to relieve intractable intracranial hypertension. Cerebral
      hemodynamic parameters prior to decompressive craniectomy and at the time of the
      XeCT CBF study were recorded. Global and regional CBF after decompressive
      craniectomy was measured using XeCT. Regional cortical CBF was measured under the
      craniectomy defect as well as for each cerebral hemisphere. Associations between
      CBF, cerebral hemodynamics, and early clinical outcome were assessed. RESULTS
      Twenty-seven patients were included in this study. The majority of patients
      (88.9%) had an initial Glasgow Coma Scale score <= 8. The median time between
      injury and decompressive surgery was 9 hours. Primary decompressive surgery
      (within 24 hours) was performed in the majority of patients (n = 18, 66.7%). Six
      patients had died by the time of discharge. XeCT CBF studies were performed a
      median of 51 hours after decompressive surgery. The mean global CBF after
      decompressive craniectomy was 49.9 +/- 21.3 ml/100 g/min. The mean cortical CBF
      under the craniectomy defect was 46.0 +/- 21.7 ml/100 g/min. Patients who were
      dead at discharge had significantly lower postcraniectomy CBF under the
      craniectomy defect (30.1 +/- 22.9 vs 50.6 +/- 19.6 ml/100 g/min; p = 0.039).
      These patients also had lower global CBF (36.7 +/- 23.4 vs 53.7 +/- 19.7 ml/100
      g/min; p = 0.09), as well as lower CBF for the ipsilateral (33.3 +/- 27.2 vs 51.8
      +/- 19.7 ml/100 g/min; p = 0.07) and contralateral (36.7 +/- 19.2 vs 55.2 +/-
      21.9 ml/100 g/min; p = 0.08) hemispheres, but these differences were not
      statistically significant. The patients who died also had significantly lower
      cerebral perfusion pressure (52 +/- 17.4 vs 75.3 +/- 10.9 mm Hg; p = 0.001).
      CONCLUSIONS In the presence of global hypoperfusion, regional cerebral
      hypoperfusion under the craniectomy defect is associated with early mortality in
      patients with TBI. Further study is needed to determine the value of
      incorporating CBF studies into clinical decision making for severe traumatic
      brain injury.

PMID- 29027861
TI  - Eloquent: history of a word's adoption into the neurosurgical lexicon.

PMID- 29027862
TI  - Effect of body mass index on outcome after aneurysmal subarachnoid hemorrhage
      treated with clipping versus coiling.
AB  - OBJECTIVE It has been suggested that increased body mass index (BMI) may confer a
      protective effect on patients who suffer from aneurysmal subarachnoid hemorrhage
      (aSAH). Whether the modality of aneurysm occlusion influences the effect of BMI
      on patient outcomes is not well understood. The authors aimed to compare the
      effect of BMI on outcomes for patients with aSAH treated with surgical clipping
      versus endovascular coiling. METHODS The authors retrospectively reviewed the
      outcomes for patients admitted to their institution for the management of aSAH
      treated with either clipping or coiling. BMI at the time of admission was
      recorded and used to assign patients to a group according to low or high BMI.
      Cutoff values for BMI were determined by classification and regression tree
      analysis. Predictors of poor functional outcome (defined as modified Rankin Scale
      score > 2 measured >= 90 days after the ictus) and posttreatment cerebral
      hypodensities detected during admission were then determined separately for
      patients treated with clipping or coiling using stepwise multivariate logistic
      regression analysis. RESULTS Of the 469 patients admitted to the authors'
      institution with aSAH who met the study's inclusion criteria, 144 were treated
      with clipping and 325 were treated with coiling. In the clipping group, the
      frequency of poor functional outcome was higher in patients with BMI >= 32.3
      kg/m2 (47.6% vs 19.0%; p = 0.007). In contrast, in the coiling group, patients
      with BMI >= 32.3 kg/m2 had a lower frequency of poor functional outcome at >= 90
      days (5.8% vs 30.9%; p < 0.001). On multivariate analysis, high BMI was
      independently associated with an increased (OR 3.92, 95% CI 1.20-13.41; p =
      0.024) and decreased (OR 0.13, 95% CI 0.03-0.40; p < 0.001) likelihood of poor
      functional outcome for patients treated with clipping and coiling, respectively.
      For patients in the surgical group, BMI >= 28.4 kg/m2 was independently
      associated with incidence of cerebral hypodensities during admission (OR 2.44,
      95% CI 1.16-5.25; p = 0.018) on multivariate analysis. For patients treated with
      coiling, BMI >= 33.2 kg/m2 was independently associated with reduced odds of
      hypodensities (OR 0.45, 95% CI 0.21-0.89; p = 0.021). CONCLUSIONS The results of
      this study suggest that BMI may differentially affect functional outcomes after
      aSAH, depending on treatment modality. These findings may aid in treatment
      selection for patients with aSAH.

PMID- 29027863
TI  - Potential utility of FLAIR in MRI-negative Cushing's disease.
AB  - OBJECTIVE Accurate presurgical localization of microadenomas in Cushing's disease
      (CD) leads to improved remission rates and decreased adverse events. Volumetric
      gradient recalled echo (3D-GRE) MRI detects pituitary microadenomas in CD in up
      to 50%-80% cases as a focus of hypointensity due to delayed contrast wash-in. The
      authors have previously reported that postcontrast FLAIR imaging may be useful in
      detecting otherwise MRI-negative pituitary microadenomas as foci of
      hyperintensity. This reflects theoretically complementary imaging of
      microadenomas due to delayed contrast washout. The authors report on the
      diagnostic accuracy and clinical utility of FLAIR imaging in the detection of
      microadenomas in patients with CD. METHODS The authors prospectively analyzed
      imaging findings in 23 patients (24 tumors) with biochemically proven CD who
      underwent transsphenoidal surgery for CD. Preoperatively, the patients underwent
      pituitary MRI with postcontrast FLAIR and postcontrast 3D-GRE sequences. RESULTS
      Postcontrast FLAIR hyperintensity was detected in macroadenomas, and in 3D-GRE
      positive or -negative microadenomas. Overall, 3D-GRE was superior in detecting
      surgically and histopathologically confirmed, location-concordant microadenomas.
      Of 24 pituitary adenomas, 18 (75%; sensitivity 82%, positive predictive value
      95%) were found on 3D-GRE, and 13 (50% [1 was false positive]; sensitivity 55%,
      positive predictive value 92%) were correctly identified on FLAIR. The stand
      alone specificity of 3D-GRE and FLAIR was similar (50%). These results confirm
      the superiority of 3D-GRE as a stand-alone imaging modality. The authors then
      tested the utility of FLAIR as a complementary tool to 3D-GRE imaging. All 5
      patients with negative 3D-GRE MRI displayed a distinct focus of FLAIR
      enhancement. Four of those 5 cases (80%) had location-concordant positive
      histopathological results and achieved postsurgical biochemical remission. The
      remaining patient was not cured, because resection did not include the region of
      FLAIR hyperintensity. CONCLUSIONS This study suggests that delayed microadenoma
      contrast washout may be detected as FLAIR hyperintensity in otherwise MRI
      negative CD cases. The authors propose adding postcontrast FLAIR sequences to
      complement 3D-GRE for surgical planning in patients with CD. Clinical trial
      registration no.: NIH protocol 03-N-0164, NCT00060541 (clinicaltrials.gov).

PMID- 29027864
TI  - Integrating computational methods to predict mutagenicity of aromatic azo
      compounds.
AB  - Azo dyes have several industrial uses. However, these azo dyes and their
      degradation products showed mutagenicity, inducing damage in environmental and
      human systems. Computational methods are proposed as cheap and rapid alternatives
      to predict the toxicity of azo dyes. A benchmark dataset of Ames data for 354 azo
      dyes was employed to develop three classification strategies using knowledge
      based methods and docking simulations. Results were compared and integrated with
      three models from the literature, developing a series of consensus strategies.
      The good results confirm the usefulness of in silico methods as a support for
      experimental methods to predict the mutagenicity of azo compounds.

PMID- 29027865
TI  - The bidirectional relation of emotion perception and social judgments: the effect
      of witness' emotion expression on perceptions of moral behaviour and vice versa.
AB  - The present research tested the notion that emotion expression and context
      perception are bidirectionally related. Specifically, in two studies focusing on
      moral violations (N = 288) and positive moral deviations (N = 245) respectively,
      we presented participants with short vignettes describing behaviours that were
      either (im)moral, (in)polite or unusual together with a picture of the emotional
      reaction of a person who supposedly had been a witness to the event. Participants
      rated both the emotional reactions observed and their own moral appraisal of the
      situation described. In both studies, we found that situational context
      influenced how emotional reactions to this context were rated and in turn, the
      emotional expression shown in reaction to a situation influenced the appraisal of
      the situation. That is, neither the moral events nor the emotion expressions were
      judged in an absolute fashion. Rather, the perception of one also depended on the
      other.

PMID- 29027866
TI  - Magnetic resonance imaging-guided laser interstitial thermal therapy as treatment
      for intractable insular epilepsy in children.
AB  - OBJECTIVE Seizure onset within the insula is increasingly recognized as a cause
      of intractable epilepsy. Surgery within the insula is difficult, with
      considerable risks, given the rich vascular supply and location near critical
      cortex. MRI-guided laser interstitial thermal therapy (LiTT) provides an
      attractive treatment option for insular epilepsy, allowing direct ablation of
      abnormal tissue while sparing nearby normal cortex. Herein, the authors describe
      their experience using this technique in a large cohort of children undergoing
      treatment of intractable localization-related epilepsy of insular onset. METHODS
      The combined epilepsy surgery database of Cook Children's Medical Center and Dell
      Children's Hospital was queried for all cases of insular onset epilepsy treated
      with LiTT. Patients without at least 6 months of follow-up data and cases
      preoperatively designated as palliative were excluded. Patient demographics,
      presurgical evaluation, surgical plan, and outcome were collected from patient
      charts and described. RESULTS Twenty patients (mean age 12.8 years, range 6.1
      18.6 years) underwent a total of 24 LiTT procedures; 70% of these patients had
      normal findings on MRI. Patients underwent a mean follow-up of 20.4 months after
      their last surgery (range 7-39 months), with 10 (50%) in Engel Class I, 1 (5%) in
      Engel Class II, 5 (25%) in Engel Class III, and 4 (20%) in Engel Class IV at last
      follow-up. Patients were discharged within 24 hours of the procedure in 15 (63%)
      cases, in 48 hours in 6 (24%) cases, and in more than 48 hours in the remaining
      cases. Adverse functional effects were experienced following 7 (29%) of the
      procedures: mild hemiparesis after 6 procedures (all patients experienced
      complete resolution or had minimal residual dysfunction by 6 months), and
      expressive language dysfunction after 1 procedure (resolved by 3 months).
      CONCLUSIONS To their knowledge, the authors present the largest cohort of
      pediatric patients undergoing insular surgery for treatment of intractable
      epilepsy. The patient outcomes suggest that LiTT can successfully treat
      intractable seizures originating within the insula and offers an attractive
      alternative to open resection. This is the first description of LiTT applied to
      insular epilepsy and represents one of only a few series describing the use of
      LiTT in children. The results indicate that seizure reduction after LiTT compares
      favorably to that after conventional open surgical techniques.

PMID- 29027867
TI  - Unplanned readmission within 90 days after pediatric neurosurgery.
AB  - OBJECTIVE Readmission and return to operating room after surgery are increasingly
      being used as a proxy for quality of care. Nearly 60% of these readmissions are
      unplanned, which translates into billions of dollars in health care costs. The
      authors set out to analyze the incidence of readmission at their center, to
      define causes of unplanned readmission, and to determine the preoperative and
      surgical variables associated with readmissions following pediatric neurosurgery.
      METHODS A total of 536 children who underwent operations for neurosurgical
      diagnoses between 2012 and 2015 and who were later readmitted were included in
      the final analysis. Unplanned readmissions were defined to have occurred as a
      result of complications within 90 days after index surgery. Patient records were
      retrospectively reviewed to determine the primary diagnosis, surgery indication,
      and cause of readmission and return to operating room. The cost for index
      hospitalization, readmission episode, and total cost were derived based on the
      charges obtained from administrative data. Bivariate and multivariable analyses
      were conducted. RESULTS Of 536 patients readmitted in total, 17.9% (n = 96) were
      readmitted within 90 days. Of the overall readmissions, 11.9% (n = 64) were
      readmitted within 30 days, and 5.97% (n = 32) were readmitted between 31 and 90
      days. The median duration between discharge and readmission was 20 days (first
      quartile [Q1]: 9 days, third quartile [Q3]: 36 days). The most common reason for
      readmission was shunt related (8.2%, n = 44), followed by wound infection (4.7%,
      n = 25). In the risk-adjusted multivariable logistic regression model for total
      90-day readmission, patients with the following characteristics: younger age (p =
      0.001, OR 0.886, 95% CI 0.824-0.952); "other" (nonwhite, nonblack) race (p =
      0.024, OR 5.49, 95% CI 1.246-24.2); and those born preterm (p = 0.032, OR 2.1,
      95% CI 1.1-4.12) had higher odds of being readmitted within 90 days after
      discharge. The total median cost for patients undergoing surgery in this study
      cohort was $11,520 (Q1: $7103, Q3: $19,264). For the patients who were
      readmitted, the median cost for a readmission episode was $8981 (Q1: $5051, Q3:
      $18,713). CONCLUSIONS Unplanned 90-day readmissions in pediatric neurosurgery are
      primarily due to CSF-related complications. Patients with the following
      characteristics: young age at presentation; "other" race; and children born
      preterm have a higher likelihood of being readmitted within 90 days after
      surgery. The median cost was > $8000, which suggests that the readmission episode
      can be as expensive as the index hospitalization. Clearly, readmission reduction
      has the potential for significant cost savings in pediatric neurosurgery. Future
      efforts, such as targeted education related to complication signs, should be
      considered in the attempt to reduce unplanned events. Given the single-center,
      retrospective study design, the results of this study are primarily applicable to
      this population and cannot necessarily be generalized to other institutions
      without further study.

PMID- 29027868
TI  - Posttraumatic complications in pediatric skull fracture: dural sinus thrombosis,
      arterial dissection, and cerebrospinal fluid leakage.
AB  - OBJECTIVE Skull fracture is associated with several intracranial injuries. The
      object of this study was to determine the rate of fracture associated with venous
      thrombosis, intracranial arterial dissection (ICAD), and cerebrospinal fluid
      (CSF) leakage in pediatric patients. Further, the authors aimed to highlight the
      features of pediatric skull fracture that predict poor neurological outcomes.
      METHOD In this retrospective study, the authors evaluated the records of 258
      pediatric patients who had incurred a traumatic skull fracture in the period from
      2009 to 2015. All the patients had undergone CT imaging, which was used to
      characterize the type of skull fracture and other important features, including
      intracranial hemorrhage. Patients with fracture extending to a dural sinus or
      proximal to major intracranial vessels had undergone vascular imaging to evaluate
      for venous thrombosis or arterial dissection. Clinical data were also reviewed
      for patients who had CSF leakage. RESULTS Two hundred fifty-eight patients had
      302 skull fractures, with 11.6% having multiple fractures. Falling was the most
      common mechanism of injury (52.3%), and the parietal bone was most frequently
      involved in the fracture (43.4%). Diastatic fracture was associated with
      increased intracranial hemorrhage (p < 0.05). The rate of venous thrombosis was
      0.4%, and the rate of ICAD was also 0.4%. The rate of CSF leakage was 2.3%. Skull
      base fracture was the only significant risk factor associated with an increased
      risk of CSF leakage (p < 0.05). There was a significant difference in fracture
      related morbidity in patients younger than versus older than 2 years of age.
      Patients younger than 2 years had fewer intracranial hemorrhages (21.8% vs 38.8%)
      and fewer neurosurgical interventions (3.0% vs 12.7%) than the patients older
      than 2 years (p < 0.001). Moreover, skull fracture in the younger group was
      mostly caused by falling (81.2% vs 33.1%); in the older group, fracture was most
      often caused by vehicle-related accidents (35.7% vs 4.0%) and being struck by or
      against an object (19.1% vs 7.9%). Additionally, skull fracture location was
      analyzed based on the mechanism of injury. Parietal bone fracture was closely
      associated with falling, and temporal bone fracture was associated with being
      struck by or against an object (p < 0.05). Frontal bone fracture was more
      associated with being struck by or against an object and vehicle-related injury
      (p < 0.05) than with falling. Vehicle-related accidents and being struck by or
      against an object, as opposed to falling, were associated with increased surgical
      intervention (13.3% vs 16.2% vs 3.7%, respectively). CONCLUSIONS Pediatric skull
      fracture usually has a benign outcome in patients who fall and are younger than 2
      years of age. Poor prognostic factors include diastasis, an age > 2 years, and
      fracture caused by vehicle-related accidents or being struck by or against an
      object. In this series, the rates of venous thrombosis and ICAD were low, and the
      authors do not advocate vascular imaging unless these disease entities are
      clinically suspected. Patients with skull base fracture should be closely
      monitored for CSF leakage.

PMID- 29027869
TI  - Acceptance of Telemonitoring Among Patients with Obstructive Sleep Apnea
      Syndrome: How is the Perceived Interest by and for Patients?
AB  - BACKGROUND: Obstructive sleep apnea syndrome, a chronic respiratory disease,
      requires regular adherence to Continuous Positive Airway Pressure (CPAP) therapy.
      Telemonitoring may be relevant to support adherence, but nonetheless this raises
      ethical issues around the intrusive nature of the daily life of patients
      Objective: To explore the acceptance of telemonitoring by patients and the impact
      of this on adherence. MATERIALS AND METHODS: A prospective and observational
      study has been performed with 160 patients who initiated their CPAP therapy. The
      acceptability of telemonitoring was studied using an attitudes' scale of 8 items.
      A total of 160 patients (111 men, 49 women) responded to the questionnaire at 1
      month upon treatment. The adoption of both telemonitoring and adherence behavior
      were observed at 10 months of therapy. RESULTS: A majority (78%) of patients
      expressed a favorable attitude toward telemonitoring, but nearly 40% consider
      this device like intrusive. However, at 10 months of treatment, 78% of patients
      are still telemonitored. We did not observe a significant difference between
      telemonitoring patients and nontelemonitoring patients with respect to the mean
      duration of use of CPAP therapy. However, the risk of stopping CPAP therapy is
      significantly more important in patients who refused telemonitoring. DISCUSSION
      AND CONCLUSION: It seems reductive to consider telemonitoring as a simple tool of
      surveillance to support adherence. It may be preferable to consider
      telemonitoring as a follow-up proposal. This will allow for more reactive
      management and close to the needs of the patients, in particular as
      telemonitoring is, in general, well accepted by patients.

PMID- 29027870
TI  - Flow diversion of a recurrent, iatrogenic basilar tip aneurysm in a pediatric
      patient: case report.
AB  - Endoscopic third ventriculostomy (ETV) is a common treatment for noncommunicating
      hydrocephalus. Although rare, vascular injury and traumatic pseudoaneurysm
      development during ETV have been reported. The authors present the case of a 13
      year-old boy who underwent repeat ETV (rETV) for shunt and ETV failure, and who
      suffered an intraoperative subarachnoid hemorrhage due to iatrogenic injury to
      the basilar tip, with subsequent development of a pseudoaneurysm. Despite initial
      primary coil embolization, the aneurysm recurred and was definitively treated
      with flow diversion. In this report, the authors review complication rates
      associated with ETV and rETV as well as the emerging use of flow diversion and
      its applications in vessel reconstruction within the pediatric population.

PMID- 29027871
TI  - Weak evidence for increased motivated forgetting of trauma-related words in
      dissociated or traumatised individuals in a directed forgetting experiment.
AB  - Motivated forgetting is the idea that people can block out, or forget, upsetting
      or traumatic memories, because there is a motivation to do so. Some researchers
      have cited directed forgetting studies using trauma-related words as evidence for
      the theory of motivated forgetting of trauma. In the current article subjects
      used the list method directed forgetting paradigm with both trauma-related words
      and positive words. After one list of words was presented subjects were directed
      to forget the words previously learned, and they then received another list of
      words. Each list was a mix of positive and trauma-related words, and the lists
      were counterbalanced. Later, subjects recalled as many of the words as they
      could, including the ones they were told to forget. Based on the theory that
      motivated forgetting would lead to recall deficits of trauma-related material, we
      created eight hypotheses. High dissociators, trauma-exposed, sexual trauma
      exposed, and high dissociators with trauma-exposure participants were
      hypothesised to show enhanced forgetting of trauma words. Results indicated only
      one of eight hypotheses was supported: those higher on dissociation and trauma
      recalled fewer trauma words in the to-be-forgotten condition, compared to those
      low on dissociation and trauma. These results provide weak support for
      differential motivated forgetting.

PMID- 29027874
TI  - Perspectives on Temperature Management.

PMID- 29027875
TI  - Human factors challenges in emergency management: enhancing individual and team
      performance in fire and emergency services.

PMID- 29027876
TI  - Intradural pathology and pathophysiology associated with Chiari I malformation in
      children and adults with and without syringomyelia.
AB  - OBJECTIVE The pathophysiology underlying tonsillar herniation and CSF obstruction
      in Chiari malformation Type I (CM-I) is unclear, and the cause of CM-I-associated
      syringomyelia is not well understood. A better understanding of this
      pathophysiology is important for an improved treatment strategy. Therefore, the
      authors sought to identify, characterize, and examine the intradural pathology
      and CSF flow pathophysiology in the posterior fossa and at the level of the
      foramen magnum that occurs in the setting of CM-I. They determined the incidence
      of these intradural findings and assessed differences across age, with the degree
      of tonsillar herniation, and in the presence and absence of syringomyelia.
      METHODS A prospective database initiated in March 2003 recorded all
      intraoperative findings during surgical treatment of children and adults with CM
      I with or without syringomyelia. A total of 389 surgeries for CM-I were performed
      in 379 patients between March 2003 and June 2016. A total of 109 surgeries were
      performed in 109 patients with CM-I (without osseoligamentous abnormalities) in
      whom both a posterior fossa extradural and intradural decompression with
      duraplasty was performed (first-time intradural procedures). Using a surgical
      microscope, intradural pathology and obstruction of CSF channels were identified
      and assessed. Student t-tests and Fisher's exact tests compared groups in a
      series of univariate analyses, followed by multivariate logistic regression.
      RESULTS The following intradural pathological entities were observed (prevalence
      noted in parentheses). These include those that did not obstruct CSF flow
      channels: opacified arachnoid (33.0%), thickened arachnoid (3.7%), ischemic and
      gliotic tonsils (40.4%), tonsillar cysts (0.9%), and inferior descent of the
      fourth ventricle and cervicomedullary junction (CMJ) (78.0%). The following
      intradural pathological entities were observed to obstruct CSF flow channels:
      medialized tonsils (100%), tonsil overlying and obstructing the foramen of
      Magendie (21.1%), intertonsillar and tonsil to CMJ arachnoid adhesions (85.3%),
      vermian posterior inferior cerebellar artery branches obstructing the foramen of
      Magendie (43.1%), and arachnoid veils or webs obstructing or occluding the
      foramen of Magendie (52.3%). Arachnoid veils varied in type and were observed in
      59.5% of patients with CM-I who had syringomyelia, which was significantly
      greater than the 33.3% of patients with CM-I without syringomyelia who had an
      arachnoid veil (p = 0.018). The presence of CM-I with an arachnoid veil had 3.22
      times the odds (p = 0.013, 95% CI 1.29-8.07, by multivariate logistic regression)
      of being associated with syringomyelia, adjusting for tonsillar herniation. The
      inferior descent of the fourth ventricle and CMJ occurred with a greater degree
      of tonsillar herniation (p < 0.001) and correlated with a cervicomedullary kink
      or buckle on preoperative MRI. CONCLUSIONS Intradural pathology associated with
      CM-I with or without syringomyelia exists in many forms, is more prevalent than
      previously recognized in patients of all ages, and may play a role in the
      pathophysiology of CM-I tonsillar herniation. Arachnoid veils appear to partially
      obstruct CSF flow, are significantly more prevalent in cases of CM-I with
      syringomyelia, and therefore may play a role in the pathophysiology of CM-I
      associated syringomyelia.

PMID- 29027877
TI  - Case report of a patient with tuberculosis of the femur after osteosynthesis with
      review of literature.

PMID- 29027878
TI  - Are Prophylactic Antibiotic Agents Indicated in Anorectal Surgery for Patients
      with Human Immunodeficiency Virus?
AB  - BACKGROUND: With increased survival among patients with human immunodeficiency
      virus (HIV), surgeons have been seeing more cases of anal dysplasia and cancer.
      There is, however, no data on the incidence of surgical site infections (SSIs) in
      HIV-positive patients undergoing elective anorectal procedures, nor on the
      administration of prophylactic antibiotic agents. We reviewed a HIV-positive
      population that has undergone elective anorectal biopsy of areas of dysplasia
      observed on office anoscopy to assess the need for antibiotic prophylaxis.
      PATIENTS AND METHODS: A retrospective chart review was performed of all HIV
      positive patients seen as outpatients in the Colorectal Surgery Division from
      2007-2016. Demographics, dates of surgery and follow-up, antibiotic prophylaxis,
      and pre-operative CD4 count and HIV viral load were recorded for 229 patients.
      Post-operative examination notes were reviewed to determine the presence of SSIs.
      The proportion of patients who received prophylaxis was assessed and the SSI rate
      was calculated. RESULTS: Surgical site infections occurred in 2 of 237 (0.8%)
      cases without antibiotic prophylaxis and in none of the 38 cases with
      prophylaxis. This infection rate was found to be lower than that of the general
      surgery population, with no statistical difference from hemorrhoidectomy patients
      without HIV. One SSI occurred in a 51-year-old male with a pre-operative CD4
      count of 612 per microliter and viral load of zero. Another occurred in a 57-year
      old female with an unknown CD4 count and viral load. A chi2 analysis showed the
      incidence of SSIs in the groups with and without prophylaxis was not
      significantly different (p = 0.563). CONCLUSION: Surgical site infection rates in
      HIV-positive patients undergoing biopsies for anal dysplasia were similar to
      patients without HIV undergoing similar minor anorectal procedures, and no
      difference was noted in the rate of SSI with the administration of prophylactic
      antibiotic agents. We do not recommend routine use of prophylactic antibiotic
      agents in this population.

PMID- 29027880
TI  - 87th Annual Meeting of the American Thyroid Association.

PMID- 29027883
TI  - Short Call Abstracts.

PMID- 29027879
TI  - Emerging Ethical Issues in Restorative Dentistry.
AB  - This article reviews some of the merging ethical issues in restorative dentistry.
      This is a branch of healthcare concerned with quality of life, since retention of
      functioning teeth is important in allowing a healthy diet to be consumed. Yet the
      supply of dentists is such that, in many of the world's poorest countries,
      extraction is the only viable option for treating tooth decay. Available repair
      materials present various ethical problems. Silver amalgam is being phased out in
      much of the world, because of environmental concerns with mercury, yet it is
      cheap and reliable. Alternatives have been developed, influenced by the West's
      preoccupation with appearance, yet these materials are difficult to place and are
      less durable than amalgam. These concerns lead to significant ethical problems,
      which are explored in this article. It concludes by proposing a way to deal with
      the emerging ethical problems.

PMID- 29027884
TI  - Accuracy and Reliability of a Handheld, Nonmydriatic Fundus Camera for the Remote
      Detection of Optic Disc Edema.
AB  - BACKGROUND: Optic disc edema can be an important indicator of serious
      neurological disease, but is poorly detected using the direct ophthalmoscope.
      Portable fundus photography may overcome this difficulty. INTRODUCTION: The
      purpose of this study was to determine the sensitivity and specificity of a
      handheld, nonmydriatic fundus camera for the detection of optic disc edema.
      MATERIALS AND METHODS: Retrospective review of nonmydriatic optic disc
      photographs taken with a portable fundus camera (Pictor Plus; Volk Optical,
      Mentor, OH) from the University of Michigan Neuro-Ophthalmology Clinics. We
      included 103 consecutive eyes with optic disc edema and 103 consecutive eyes
      without optic disc edema of 109 patients. Four masked neuro-ophthalmologists
      graded a single photograph of each optic disc presented in randomized order and
      documented the presence of optic disc edema. Sensitivity and specificity of
      graders' photographic interpretation was compared with clinical examinations.
      Reliability of assessments within and between graders was determined using kappa
      statistics. RESULTS: The sensitivity and specificity for detection of optic disc
      edema were 71.8-92.2% and 81.6-95.2%, respectively. Photos were found to be
      ungradable in 0-8.3% of cases. The intergrader reliabilities ranged from 0.60
      [95% confidence interval (CI): 0.52-0.67] to 0.72 (95% CI: 0.66-0.77).
      Intragrader reliability ranged from 0.76 (95% CI: 0.63-0.92) to 0.82 (95% CI:
      0.69-0.95). DISCUSSION: Photographs taken with portable, nonmydriatic technology
      met threshold sensitivity and specificity for remote screening for optic disc
      edema when performed by most, but not all graders. Reliability between graders
      was moderate-strong and strong within individual providers. CONCLUSIONS: Portable
      photography holds promise for use in remote screening of optic disc edema.

PMID- 29027885
TI  - Therapeutic Hypothermia in Postcardiac Arrest.

PMID- 29027886
TI  - Molecular Typing of Bois Noir Phytoplasma Strains in the Chianti Classico Area
      (Tuscany, Central Italy) and Their Association with Symptom Severity in Vitis
      vinifera 'Sangiovese'.
AB  - Bois noir (BN) is the most widespread disease of the grapevine yellows complex in
      the Euro-Mediterranean area. BN is caused by 'Candidatus Phytoplasma solani'
      (BNp), transmitted from herbaceous plants to grapevine by polyphagous insect
      vectors. In this study, genetic diversity among BNp strains and their prevalence
      and possible association with grapevine symptom severity were investigated in a
      Sangiovese clone organic vineyard in the Chianti Classico area (Tuscany). Field
      surveys over 2 years revealed a range of symptom severity on grapevine and an
      increase of BN incidence. A TaqMan allelic discrimination assay detected only
      tufB type b among BNp strains, suggesting the prevalence of the bindweed-related
      ecology. Nucleotide sequence analyses of vmp1 and stamp genes identified 12 vmp1
      and 16 stamp sequence variants, showing an overall positive selection for such
      genes. The prevalent genotype was Vm43/St10, reported for the first time in this
      study and closely related to strains identified only in the French Eastern
      Pyrenees. BNp strains identified in the examined vineyard and mostly grouped in
      separate bindweed-related phylogenetic clusters showed statistically significant
      differences in their distribution in grapevines exhibiting distinct symptom
      severity. These results suggest the possible occurrence of a range of virulence
      within BNp strain populations in the Chianti Classico area.

PMID- 29027887
TI  - Frequent Shifts in Aspergillus flavus Populations Associated with Maize
      Production in Sonora, Mexico.
AB  - Aspergillus flavus frequently contaminates maize, a critical staple for billions
      of people, with aflatoxins. Diversity among A. flavus L morphotype populations
      associated with maize in Sonora, Mexico was assessed and, in total, 869 isolates
      from 83 fields were placed into 136 vegetative compatibility groups (VCGs) using
      nitrate-nonutilizing mutants. VCG diversity indices did not differ in four
      agroecosystems (AES) but diversity significantly differed among years.
      Frequencies of certain VCGs changed manyfold over single years in both multiple
      fields and multiple AES. Certain VCGs were highly frequent (>1%) in 2006 but
      frequencies declined repeatedly in each of the two subsequent years. Other VCGs
      that had low frequencies in 2006 increased in 2007 and subsequently declined.
      None of the VCGs were consistently associated with any AES. Fourteen VCGs were
      considered dominant in at least a single year. However, frequencies often varied
      significantly among years. Only 9% of VCGs were detected all 3 years whereas 66%
      were detected in only 1 year. Results suggest that the most realistic
      measurements of both genetic diversity and the frequency of A. flavus VCGs are
      obtained by sampling multiple locations in multiple years. Single-season sampling
      in many locations should not be substituted for sampling over multiple years.

PMID- 29027889
TI  - Cure rate modelling.

PMID- 29027888
TI  - Same-Hospital Re-Admission Rate Is Not Reliable for Measuring Post-Operative
      Infection-Related Re-Admission.
AB  - BACKGROUND: Post-operative infections cause morbidity, consume resources, and are
      an important quality measure in assessing and comparing hospitals. Commonly used
      metrics do not account for re-admission to a different hospital. The Nationwide
      Readmissions Database (NRD) tracks re-admissions across United States (US)
      hospitals. Infection-related re-admission across US hospitals has not been
      studied previously. PATIENTS AND METHODS: The 2013 NRD was queried for admissions
      with a primary International Classification of Diseases and Related Health
      Problems, 9th revision, Clinical Modification code for the most frequently
      performed operations. Non-elective all-cause, infection-related, and different
      hospital 30-day re-admission rates were calculated, using All Patient Refined
      Diagnosis Related Groups codes. Multi-variable logistic regression identified
      risk factors for re-admission. RESULTS: Of 826,836 surviving to discharge, 39,281
      (4.8%) had an unplanned re-admission within 30 days, occurring at a different
      hospital 20.5% of the time. The most common reason for re-admission was infection
      (25.1%). Orthopedic and spinal procedures were at highest risk for all-cause and
      infection-related different hospital re-admission. Infection-related different
      hospital re-admission risk factors included: Length of stay >30 days (odds ratio
      [OR] 2.28 [1.62-3.21], p < 0.01), age >=65 years (OR 1.56 [1.38-1.76], p < 0.01),
      and Charlson Comorbidity Index >1 (OR 1.14 [1.01-1.28], p < 0.01) and differed
      from predictors of same-hospital infectious re-admission. Non-elective surgical
      procedure (OR 0.79 [0.72-0.87], p < 0.01) and initial hospitalization at a large
      hospital (OR 0.66 [0.59-0.74], p < 0.01) were protective. CONCLUSION: A
      substantial proportion of post-operative re-admissions are missed by same
      hospital re-admission data. All-cause and infection-related post-operative re
      admissions to a different hospital are affected by unique patient and institution
      specific factors. Re-admission reduction programs, quality metrics, and policy
      based on same hospital re-admission data should be updated to incorporate
      different hospital re-admission.

PMID- 29027890
TI  - Corrigendum.

PMID- 29027891
TI  - Editorial Board - End-of-volume.

PMID- 29027892
TI  - The Lives of Older Lesbians: Sexuality, Identity and the Life Course.

PMID- 29027893
TI  - Hospital-acquired conditions: predictors and implications for outcomes following
      spine tumor resection.
AB  - OBJECTIVE Hospital-acquired conditions (HACs) significantly compromise patient
      safety, and have been identified by the Centers for Medicare and Medicaid
      Services as events that will be associated with penalties for surgeons. The
      mitigation of HACs must be an important consideration during the postoperative
      management of patients undergoing spine tumor resection. The purpose of this
      study was to identify the risk factors for HACs and to characterize the
      relationship between HACs and other postoperative adverse events following spine
      tumor resection. METHODS The 2008-2014 American College of Surgeons' National
      Surgical Quality Improvement Program database was used to identify adult patients
      undergoing the resection of intramedullary, intradural extramedullary, and
      extradural spine lesions via current procedural terminology and ICD-9 codes.
      Demographic, comorbidity, and operative variables were evaluated via bivariate
      statistics before being incorporated into a multivariable logistic regression
      model to identify the independent risk factors for HACs. Associations between
      HACs and other postoperative events, including death, readmission, prolonged
      length of stay, and various complications were determined through multivariable
      analysis while controlling for other significant variables. The c-statistic was
      computed to evaluate the predictive capacity of the regression models. RESULTS Of
      the 2170 patients included in the study, 195 (9.0%) developed an HAC. Only 2
      perioperative variables, functional dependency and high body mass index, were
      risk factors for developing HACs (area under the curve = 0.654). Hospital
      acquired conditions were independent predictors of all examined outcomes and
      complications, including death (OR 2.26, 95% CI 1.24-4.11, p = 0.007), prolonged
      length of stay (OR 2.74, 95% CI 1.98-3.80, p < 0.001), and readmission (OR 9.16,
      95% CI 6.27-13.37, p < 0.001). The areas under the curve for these models ranged
      from 0.750 to 0.917. CONCLUSIONS The comorbidities assessed in this study were
      not strongly predictive of HACs. Other variables, including hospital-associated
      factors, may play a role in the development of these conditions. The presence of
      an HAC was found to be an independent risk factor for a variety of adverse
      events. These findings highlight the need for continued development of evidence
      based protocols designed to reduce the incidence and severity of HACs.

PMID- 29027894
TI  - Editorial. The clinical and economic costs of treating cervical radiculopathy:
      the age-old question of the anterior versus posterior approach.

PMID- 29027895
TI  - Changes in foraminal area with anterior decompression versus keyhole foraminotomy
      in the cervical spine: a biomechanical investigation.
AB  - OBJECTIVE Anterior cervical discectomy and fusion (ACDF) with or without partial
      uncovertebral joint resection (UVR) and posterior keyhole foraminotomy are
      established operative procedures to treat cervical disc degeneration and
      radiculopathy. Studies have demonstrated reliable results with each procedure,
      but none have compared the change in neuroforaminal area between indirect and
      direct decompression techniques. The purpose of this study was to determine which
      cervical decompression method most consistently increases neuroforaminal area and
      how that area is affected by neck position. METHODS Eight human cervical
      functional spinal units (4 each of C5-6 and C6-7) underwent sequential
      decompression. Each level received the following surgical treatment: bilateral
      foraminotomy, ACDF, ACDF + partial UVR, and foraminotomy + ACDF. Multidirectional
      pure moment flexibility testing combined with 3D C-arm imaging was performed
      after each procedure to measure the minimum cross-sectional area of each foramen
      in 3 different neck positions: neutral, flexion, and extension. RESULTS
      Neuroforaminal area increased significantly with foraminotomy versus intact in
      all positions. These area measurements did not change in the ACDF group through
      flexion-extension. A significant decrease in area was observed for ACDF in
      extension (40 mm2) versus neutral (55 mm2). Foraminotomy + ACDF did not
      significantly increase area compared with foraminotomy in any position. The UVR
      procedure did not produce any changes in area through flexion-extension.
      CONCLUSIONS All procedures increased neuroforaminal area. Foraminotomy and
      foraminotomy + ACDF produced the greatest increase in area and also maintained
      the area in extension more than anterior-only procedures. The UVR procedure did
      not significantly alter the area compared with ACDF alone. With a stable cervical
      spine, foraminotomy may be preferable to directly decompress the neuroforamen;
      however, ACDF continues to play an important role for indirect decompression and
      decompression of more centrally located herniated discs. These findings pertain
      to bony stenosis of the neuroforamen and may not apply to soft disc herniation.
      The key points of this study are as follows. Both ACDF and foraminotomy increase
      the foraminal space. Foraminotomy was most successful in maintaining these
      increases during neck motion. Partial UVR was not a significant improvement over
      ACDF alone. Foraminotomy may be more efficient at decompressing the neuroforamen.
      Results should be taken into consideration only with stable spines.

PMID- 29027896
TI  - Molluscum contagiosum and pubic hair removal in male patients.

PMID- 29027897
TI  - Congenital syphilis in England and amendments to the BASHH guideline for
      management of affected infants.

PMID- 29027898
TI  - Surgery versus Antibiotics for Uncomplicated Appendicitis: Which Would a Medical
      Student Want?
AB  - BACKGROUND: Recent data suggest that treatment of acute, uncomplicated
      appendicitis (AUA) with antibiotics is as effective as surgery. A 2015 study
      indicated that more than 50% of patients would choose antibiotic therapy. Medical
      students represent a unique population of potential patients with greater medical
      knowledge than the general public and possibly less bias than practicing
      physicians. Therefore, we aimed to evaluate what the MEDICAL STUDENT'S treatment
      choice for AUA would be and what factors influence these decisions. METHODS: We
      conducted a survey of current medical students at a single institution. Survey
      data included demographics, interest in surgery or a procedure-related specialty,
      knowledge of and experience with surgery and antibiotics, and concerns about
      treatments. A summary of the literature regarding the efficacy and safety of
      antibiotics and surgery was presented. Each participant was asked which treatment
      he or she would choose if affected by AUA. RESULTS: A series of 255 medical
      students completed the survey (mean age 24.8 +/- 2.4 y; 51.5% female). The
      largest number of respondents (41.2%) were second-year students, and more than
      half (54.2%) reported an interest in a procedure-related specialty. Nearly all
      (93%) reported prior antibiotic use (19% reporting adverse effects), and 50% had
      prior surgery (20% reporting adverse events). When asked to identify concerns
      about each treatment choice, "surgical complications" was selected most
      frequently (82%) for surgery, and "adverse events and side effects" was selected
      most frequently for antibiotics (57%). When asked how they would treat their own
      AUA, 66.3% selected surgery, 24.3% selected antibiotics, and 9.4% were unsure.
      Race, gender, specialty of interest, year of training, and history of adverse
      effects related to antibiotics or surgery were not significantly related to
      treatment choice (all p > 0.1). CONCLUSION: When informed of the benefits and
      risks of surgery and antibiotics to treat AUA, medical students in our study were
      more likely to choose surgery.

PMID- 29027899
TI  - Metformin extends C. elegans lifespan through lysosomal pathway.
AB  - Metformin, a widely used first-line drug for treatment of type 2 diabetes (T2D),
      has been shown to extend lifespan and delay the onset of age-related diseases.
      However, its primary locus of action remains unclear. Using a pure in vitro
      reconstitution system, we demonstrate that metformin acts through the v-ATPase
      Ragulator lysosomal pathway to coordinate mTORC1 and AMPK, two hubs governing
      metabolic programs. We further show in Caenorhabditis elegans that both v-ATPase
      mediated TORC1 inhibition and v-ATPase-AXIN/LKB1-mediated AMPK activation
      contribute to the lifespan extension effect of metformin. Elucidating the
      molecular mechanism of metformin regulated healthspan extension will boost its
      therapeutic application in the treatment of human aging and age-related diseases.

PMID- 29027900
TI  - RNA polymerase II stalling at pre-mRNA splice sites is enforced by ubiquitination
      of the catalytic subunit.
AB  - Numerous links exist between co-transcriptional RNA processing and the
      transcribing RNAPII. In particular, pre-mRNA splicing was reported to be
      associated with slowed RNAPII elongation. Here, we identify a site of
      ubiquitination (K1246) in the catalytic subunit of RNAPII close to the DNA entry
      path. Ubiquitination was increased in the absence of the Bre5-Ubp3 ubiquitin
      protease complex. Bre5 binds RNA in vivo, with a preference for exon 2 regions of
      intron-containing pre-mRNAs and poly(A) proximal sites. Ubiquitinated RNAPII
      showed similar enrichment. The absence of Bre5 led to impaired splicing and
      defects in RNAPII elongation in vivo on a splicing reporter construct. Strains
      expressing RNAPII with a K1246R mutation showed reduced co-transcriptional
      splicing. We propose that ubiquinitation of RNAPII is induced by RNA processing
      events and linked to transcriptional pausing, which is released by Bre5-Ubp3
      associated with the nascent transcript.

PMID- 29027901
TI  - Structure of RNA polymerase bound to ribosomal 30S subunit.
AB  - In bacteria, mRNA transcription and translation are coupled to coordinate optimal
      gene expression and maintain genome stability. Coupling is thought to involve
      direct interactions between RNA polymerase (RNAP) and the translational
      machinery. We present cryo-EM structures of E. coli RNAP core bound to the small
      ribosomal 30S subunit. The complex is stable under cell-like ionic conditions,
      consistent with functional interaction between RNAP and the 30S subunit. The RNA
      exit tunnel of RNAP aligns with the Shine-Dalgarno-binding site of the 30S
      subunit. Ribosomal protein S1 forms a wall of the tunnel between RNAP and the 30S
      subunit, consistent with its role in directing mRNAs onto the ribosome. The
      nucleic-acid-binding cleft of RNAP samples distinct conformations, suggesting
      different functional states during transcription-translation coupling. The
      architecture of the 30S*RNAP complex provides a structural basis for co
      localization of the transcriptional and translational machineries, and inform
      future mechanistic studies of coupled transcription and translation.

PMID- 29027902
TI  - Independent manipulation of histone H3 modifications in individual nucleosomes
      reveals the contributions of sister histones to transcription.
AB  - Histone tail modifications can greatly influence chromatin-associated processes.
      Asymmetrically modified nucleosomes exist in multiple cell types, but whether
      modifications on both sister histones contribute equally to chromatin dynamics
      remains elusive. Here, we devised a bivalent nucleosome system that allowed for
      the constitutive assembly of asymmetrically modified sister histone H3s in
      nucleosomes in Saccharomyces cerevisiae. The sister H3K36 methylations
      independently affected cryptic transcription in gene coding regions, whereas
      sister H3K79 methylation had cooperative effects on gene silencing near
      telomeres. H3K4 methylation on sister histones played an independent role in
      suppressing the recruitment of Gal4 activator to the GAL1 promoter and in
      inhibiting GAL1 transcription. Under starvation stress, sister H3K4 methylations
      acted cooperatively, independently or redundantly to regulate transcription.
      Thus, we provide a unique tool for comparing symmetrical and asymmetrical
      modifications of sister histone H3s in vivo.

PMID- 29027904
TI  - Self-assembly of model proteins into virus capsids.
AB  - We consider self-assembly of proteins into a virus capsid by the methods of
      molecular dynamics. The capsid corresponds either to SPMV or CCMV and is studied
      with and without the RNA molecule inside. The proteins are flexible and described
      by the structure-based coarse-grained model augmented by electrostatic
      interactions. Previous studies of the capsid self-assembly involved solid objects
      of a supramolecular scale, e.g. corresponding to capsomeres, with engineered
      couplings and stochastic movements. In our approach, a single capsid is
      dissociated by an application of a high temperature for a variable period and
      then the system is cooled down to allow for self-assembly. The restoration of the
      capsid proceeds to various extent, depending on the nature of the dissociated
      state, but is rarely complete because some proteins depart too far unless the
      process takes place in a confined space.

PMID- 29027905
TI  - Electron transport and room temperature single-electron charging in 10 nm scale
      PtC nanostructures formed by electron beam induced deposition.
AB  - Nanostructures of platinum-carbon nanocomposite material have been formed by
      electron-beam induced deposition. These consist of nanodots and nanowires with a
      minimum size ~20 nm, integrated within ~100 nm nanogap n-type silicon-on
      insulator transistor structures. The nanodot transistors use ~20 nm Pt/C
      nanodots, tunnel-coupled to Pt/C nanowire electrodes, bridging the Si nanogaps.
      Room-temperature single-electron transistor operation has been measured, and
      single-electron current oscillations and 'Coulomb diamonds' observed. In nanowire
      transistors, the temperature dependence from 290 to 8 K suggests that the current
      is a combination of thermally activated and tunnelling transport of carriers
      across potential barriers along the current path, and that the Pt/C is p-type at
      low temperature.

PMID- 29027903
TI  - Functional dichotomy in spinal- vs prefrontal-projecting locus coeruleus modules
      splits descending noradrenergic analgesia from ascending aversion and anxiety in
      rats.
AB  - The locus coeruleus (LC) projects throughout the brain and spinal cord and is the
      major source of central noradrenaline. It remains unclear whether the LC acts
      functionally as a single global effector or as discrete modules. Specifically,
      while spinal-projections from LC neurons can exert analgesic actions, it is not
      known whether they can act independently of ascending LC projections. Using viral
      vectors taken up at axon terminals, we expressed chemogenetic actuators
      selectively in LC neurons with spinal (LC:SC) or prefrontal cortex (LC:PFC)
      projections. Activation of the LC:SC module produced robust, lateralised anti
      nociception while activation of LC:PFC produced aversion. In a neuropathic pain
      model, LC:SC activation reduced hind-limb sensitisation and induced conditioned
      place preference. By contrast, activation of LC:PFC exacerbated spontaneous pain,
      produced aversion and increased anxiety-like behaviour. This independent,
      contrasting modulation of pain-related behaviours mediated by distinct
      noradrenergic neuronal populations provides evidence for a modular functional
      organisation of the LC.

PMID- 29027906
TI  - Directed assembly-based printing of homogeneous and hybrid nanorods using
      dielectrophoresis.
AB  - Printing nano and microscale three-dimensional (3D) structures using directed
      assembly of nanoparticles has many potential applications in electronics,
      photonics and biotechnology. This paper presents a reproducible and scalable 3D
      dielectrophoresis assembly process for printing homogeneous silica and hybrid
      silica/gold nanorods from silica and gold nanoparticles. The nanoparticles are
      assembled into patterned vias under a dielectrophoretic force generated by an
      alternating current (AC) field, and then completely fused in situ to form
      nanorods. The assembly process is governed by the applied AC voltage amplitude
      and frequency, pattern geometry, and assembly time. Here, we find out that
      complete assembly of nanorods is not possible without applying both
      dielectrophoresis and electrophoresis. Therefore, a direct current offset voltage
      is used to add an additional electrophoretic force to the assembly process. The
      assembly can be precisely controlled to print silica nanorods with diameters from
      20-200 nm and spacing from 500 nm to 2 MUm. The assembled nanorods have good
      uniformity in diameter and height over a millimeter scale. Besides homogeneous
      silica nanorods, hybrid silica/gold nanorods are also assembled by sequentially
      assembling silica and gold nanoparticles. The precision of the assembly process
      is further demonstrated by assembling a single particle on top of each nanorod to
      demonstrate an additional level of functionalization. The assembled hybrid
      silica/gold nanorods have potential to be used for metamaterial applications that
      require nanoscale structures as well as for plasmonic sensors for biosensing
      applications.

PMID- 29027907
TI  - Negative thermophoresis of nanoparticles interacting with fluids through a purely
      repulsive potential.
AB  - Thermophoretic forces acting on nanoparticles are investigated using molecular
      dynamics simulation. We assume the Lennard-Jones (LJ) potential for the
      interaction between fluid molecules. On the other hand, the interaction between
      the nanoparticle and the surrounding fluid molecules are assumed to be either LJ
      or Weeks-Chandler-Andersen (WCA) potential, where the latter is purely-repulsive.
      The effect of the interaction potential on the thermophoretic force is
      investigated for various situations. It is found that the thermophoretic force
      basically acts in the direction from the hotter side to the colder side of the
      nanoparticle. However, when the surrounding fluid is in the liquid phase, the
      force acts in the reversed direction for the case of the WCA potential. It is
      clarified that the sign reversal is caused by the different structures observed
      in the distribution of repulsive forces acting on the nanoparticle.

PMID- 29027908
TI  - Large energy storage efficiency of the dielectric layer of graphene
      nanocapacitors.
AB  - Electric capacitors are commonly used in electronic circuits for the short-term
      storage of small amounts of energy. It is desirable however to use capacitors to
      store much larger energy amounts to replace rechargeable batteries. Unfortunately
      existing capacitors cannot store sufficient energy to be able to replace common
      electrochemical energy storage systems. Here we examine the energy storage
      capabilities of graphene nanocapacitors, which are tri-layer devices involving an
      Al film, Al2O3 dielectric layer, and a single layer of carbon atoms, i.e.,
      graphene. This is a purely electronic capacitor and therefore it can function in
      a wide temperature interval. The capacitor shows a high dielectric breakdown
      electric field strength, of the order of 1000 kV mm-1 (i.e., 1 GV m-1), which is
      much larger than the table value of the Al2O3 dielectric strength. The
      corresponding energy density is 10-100 times larger than the energy density of a
      common electrolytic capacitor. Moreover, we discover that the amount of charge
      stored in the dielectric layer can be equal or can even exceed the amount of
      charge stored on the capacitor plates. The dielectric discharge current follows a
      power-law time dependence. We suggest a model to explain this behavior.

PMID- 29027909
TI  - Cytotoxicity and cellular uptake of different sized gold nanoparticles in ovarian
      cancer cells.
AB  - Nanomedicine has advanced the biomedical field with the availability of
      multifunctional nanoparticles (NPs) systems that can target a disease site
      enabling drug delivery and helping to monitor the disease. In this paper, we
      synthesised the gold nanoparticles (AuNPs) with an average size 18, 40, 60 and 80
      nm, and studied the effect of nanoparticles size, concentration and incubation
      time on ovarian cancer cells namely, OVCAR5, OVCAR8, and SKOV3. The size measured
      by transmission electron microscopy images was slightly smaller than the
      hydrodynamic diameter; measured size by ImageJ as 14.55, 38.13, 56.88 and 78.56
      nm. The cellular uptake was significantly controlled by the AuNPs size,
      concentration, and the cell type. The nanoparticles uptake increased with
      increasing concentration, and 18 and 80 nm AuNPs showed higher uptake ranging
      from 1.3 to 5.4 MUg depending upon the concentration and cell type. The AuNPs
      were associated with a temporary reduction in metabolic activity, but metabolic
      activity remained more than 60% for all sample types; NPs significantly affected
      the cell proliferation activity in first 12 h. The increase in nanoparticle size
      and concentration induced the production of reactive oxygen species in 24 h.

PMID- 29027910
TI  - A LQR-Based Controller with Estimation of Road Bank for Improving Vehicle Lateral
      and Rollover Stability via Active Suspension.
AB  - In this article, a Linear Quadratic Regulator (LQR) lateral stability and
      rollover controller has been developed including as the main novelty taking into
      account the road bank angle and using exclusively active suspension for both
      lateral stability and rollover control. The main problem regarding the road bank
      is that it cannot be measured by means of on-board sensors. The solution proposed
      in this article is performing an estimation of this variable using a Kalman
      filter. In this way, it is possible to distinguish between the road disturbance
      component and the vehicle's roll angle. The controller's effectiveness has been
      tested by means of simulations carried out in TruckSim, using an experimentally
      validated vehicle model. Lateral load transfer, roll angle, yaw rate and sideslip
      angle have been analyzed in order to quantify the improvements achieved on the
      behavior of the vehicle. For that purpose, these variables have been compared
      with the results obtained from both a vehicle that uses passive suspension and a
      vehicle using a fuzzy logic controller.

PMID- 29027911
TI  - Outlier Detection for Sensor Systems (ODSS): A MATLAB Macro for Evaluating
      Microphone Sensor Data Quality.
AB  - Microphone sensor systems provide information that may be used for a variety of
      applications. Such systems generate large amounts of data. One concern is with
      microphone failure and unusual values that may be generated as part of the
      information collection process. This paper describes methods and a MATLAB
      graphical interface that provides rapid evaluation of microphone performance and
      identifies irregularities. The approach and interface are described. An
      application to a microphone array used in a wind tunnel is used to illustrate the
      methodology.

PMID- 29027914
TI  - Fabrication and Characterization of a Stabilized Thin Film Ag/AgCl Reference
      Electrode Modified with Self-Assembled Monolayer of Alkane Thiol Chains for Rapid
      Biosensing Applications.
AB  - The fabrication of miniaturized electrical biosensing devices can enable the
      rapid on-chip detection of biomarkers such as miRNA molecules, which is highly
      important in early-stage cancer detection. The challenge in realizing such
      devices remains in the miniaturization of the reference electrodes, which is an
      integral part of electrical detection. Here, we report on a novel thin film
      Ag/AgCl reference electrode (RE) that has been fabricated on top of a Au
      sputtered glass surface, which was coated with a self-assembled monolayer (SAM)
      of 6-mercepto-1-hexanol (MCH). The electrode showed very little measurement
      deviation (-1.5 mv) from a commercial Ag/AgCl reference electrode and exhibited a
      potential drift of only +/- 0.2 mV/h. In addition, the integration of this SAM
      modified microfabricated thin film RE enabled the rapid detection (<30 min) of
      miRNA (let-7a). The electrode can be integrated seamlessly into a microfluidic
      device, allowing the highly stable and fast measurement of surface potential and
      is expected to be very useful for the development of miniature electrical
      biosensors.

PMID- 29027913
TI  - Neural Hyperexcitability in Autism Spectrum Disorders.
AB  - Despite the progress that has been made in research on autism spectrum disorders
      (ASD), the understanding of the biological basis of ASD to identify targets for
      novel, effective treatment remains limited. One of the leading biological
      theories of autism is a model of cortical hyperexcitability. While numerous
      genetic and epigenetic studies support this model, how this particular biological
      alteration relates to known phenotypes in ASD is not well established. Using
      examples of sensory processing alterations, this review illustrates how cortical
      excitability may affect neural processes to result eventually in some core
      clinical phenotypes in ASD. Applications of the cortical excitability model for
      translational research and drug development are also discussed.

PMID- 29027912
TI  - Guanidinium Toxins and Their Interactions with Voltage-Gated Sodium Ion Channels.
AB  - Guanidinium toxins, such as saxitoxin (STX), tetrodotoxin (TTX) and their
      analogs, are naturally occurring alkaloids with divergent evolutionary origins
      and biogeographical distribution, but which share the common chemical feature of
      guanidinium moieties. These guanidinium groups confer high biological activity
      with high affinity and ion flux blockage capacity for voltage-gated sodium
      channels (NaV). Members of the STX group, known collectively as paralytic
      shellfish toxins (PSTs), are produced among three genera of marine
      dinoflagellates and about a dozen genera of primarily freshwater or brackish
      water cyanobacteria. In contrast, toxins of the TTX group occur mainly in
      macrozoa, particularly among puffer fish, several species of marine invertebrates
      and a few terrestrial amphibians. In the case of TTX and analogs, most evidence
      suggests that symbiotic bacteria are the origin of the toxins, although
      endogenous biosynthesis independent from bacteria has not been excluded. The
      evolutionary origin of the biosynthetic genes for STX and analogs in
      dinoflagellates and cyanobacteria remains elusive. These highly potent molecules
      have been the subject of intensive research since the latter half of the past
      century; first to study the mode of action of their toxigenicity, and later as
      tools to characterize the role and structure of NaV channels, and finally as
      therapeutics. Their pharmacological activities have provided encouragement for
      their use as therapeutants for ion channel-related pathologies, such as pain
      control. The functional role in aquatic and terrestrial ecosystems for both
      groups of toxins is unproven, although plausible mechanisms of ion channel
      regulation and chemical defense are often invoked. Molecular approaches and the
      development of improved detection methods will yield deeper understanding of
      their physiological and ecological roles. This knowledge will facilitate their
      further biotechnological exploitation and point the way towards development of
      pharmaceuticals and therapeutic applications.

PMID- 29027916
TI  - A Next-Generation Sequencing Approach Uncovers Viral Transcripts Incorporated in
      Poxvirus Virions.
AB  - Transcripts are known to be incorporated in particles of DNA viruses belonging to
      the families of Herpesviridae and Mimiviridae, but the presence of transcripts in
      other DNA viruses, such as poxviruses, has not been analyzed yet. Therefore, we
      first established a next-generation-sequencing (NGS)-based protocol, enabling the
      unbiased identification of transcripts in virus particles. Subsequently, we
      applied our protocol to analyze RNA in an emerging zoonotic member of the
      Poxviridae family, namely Cowpox virus. Our results revealed the incorporation of
      19 viral transcripts, while host identifications were restricted to ribosomal and
      mitochondrial RNA. Most viral transcripts had an unknown and immunomodulatory
      function, suggesting that transcript incorporation may be beneficial for poxvirus
      immune evasion. Notably, the most abundant transcript originated from the D5L/I1R
      gene that encodes a viral inhibitor of the host cytoplasmic DNA sensing
      machinery.

PMID- 29027915
TI  - A Combination of Immune Checkpoint Inhibition with Metronomic Chemotherapy as a
      Way of Targeting Therapy-Resistant Cancer Cells.
AB  - Therapeutic resistance remains a major obstacle in treating many cancers,
      particularly in advanced stages. It is likely that cytotoxic lymphocytes (CTLs)
      have the potential to eliminate therapy-resistant cancer cells. However, their
      effectiveness may be limited either by the immunosuppressive tumor
      microenvironment, or by immune cell death induced by cytotoxic treatments. High
      frequency low-dose (also known as metronomic) chemotherapy can help improve the
      activity of CTLs by providing sufficient stimulation for cytotoxic immune cells
      without excessive depletion. Additionally, therapy-induced removal of tumor cells
      that compete for shared nutrients may also facilitate tumor infiltration by CTLs,
      further improving prognosis. Metronomic chemotherapy can also decrease the number
      of immunosuppressive cells in the tumor microenvironment, including regulatory T
      cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Immune checkpoint
      inhibition can further augment anti-tumor immune responses by maintaining T cells
      in an activated state. Combining immune checkpoint inhibition with metronomic
      administration of chemotherapeutic drugs may create a synergistic effect that
      augments anti-tumor immune responses and clears metabolic competition. This would
      allow immune-mediated elimination of therapy-resistant cancer cells, an effect
      that may be unattainable by using either therapeutic modality alone.

PMID- 29027917
TI  - Porcine Dental Epithelial Cells Differentiated in a Cell Sheet Constructed by
      Magnetic Nanotechnology.
AB  - Magnetic nanoparticles (MNPs) are widely used in medical examinations,
      treatments, and basic research, including magnetic resonance imaging, drug
      delivery systems, and tissue engineering. In this study, MNPs with magnetic force
      were applied to tissue engineering for dental enamel regeneration. The
      internalization of MNPs into the odontogenic cells was observed by transmission
      electron microscopy. A combined cell sheet consisting of dental epithelial cells
      (DECs) and dental mesenchymal cells (DMCs) (CC sheet) was constructed using
      magnetic force-based tissue engineering technology. The result of the iron
      staining indicated that MNPs were distributed ubiquitously over the CC sheet.
      mRNA expression of enamel differentiation and basement membrane markers was
      examined in the CC sheet. Immunostaining showed Collagen IV expression at the
      border region between DEC and DMC layers in the CC sheet. These results revealed
      that epithelial-mesenchymal interactions between DEC and DMC layers were caused
      by bringing DECs close to DMCs mechanically by magnetic force. Our study suggests
      that the microenvironment in the CC sheet might be similar to that during the
      developmental stage of a tooth bud. In conclusion, a CC sheet employing MNPs
      could be developed as a novel and unique graft for artificially regenerating
      dental enamel.

PMID- 29027918
TI  - Temperature Influences the Production and Transport of Saxitoxin and the
      Expression of sxt Genes in the Cyanobacterium Aphanizomenon gracile.
AB  - The cyanobacterium Aphanizomenon gracile is the most widely distributed producer
      of the potent neurotoxin saxitoxin in freshwaters. In this work, total and
      extracellular saxitoxin and the transcriptional response of three genes linked to
      saxitoxin biosynthesis (sxtA) and transport (sxtM, sxtPer) were assessed in
      Aphanizomenon gracile UAM529 cultures under temperatures covering its annual
      cycle (12  degrees C, 23  degrees C, and 30  degrees C). Temperature influenced
      saxitoxin production being maximum at high temperatures (30  degrees C) above the
      growth optimum (23  degrees C), concurring with a 4.3-fold increased sxtA
      expression at 30  degrees C. Extracellular saxitoxin transport was temperature
      dependent, with maxima at extremes of temperature (12  degrees C with 16.9%
      extracellular saxitoxin; and especially 30  degrees C with 53.8%) outside the
      growth optimum (23  degrees C), coinciding with a clear upregulation of sxtM at
      both 12  degrees C and 30  degrees C (3.8-4.1 fold respectively), and yet with
      just a slight upregulation of sxtPer at 30  degrees C (2.1-fold). Nitrate
      depletion also induced a high extracellular saxitoxin release (51.2%), although
      without variations of sxtM and sxtPer transcription, and showing evidence of
      membrane damage. This is the first study analysing the transcriptional response
      of sxtPer under environmental gradients, as well as the effect of temperature on
      putative saxitoxin transporters (sxtM and sxtPer) in cyanobacteria in general.

PMID- 29027920
TI  - Fingertip Fiber Optical Tactile Array with Two-Level Spring Structure.
AB  - Tactile perception is a feature benefiting reliable grasping and manipulation.
      This paper presents the design of an integrated fingertip force sensor employing
      an optical fiber based approach where applied forces modulate light intensity.
      The proposed sensor system is developed to support grasping of a broad range of
      objects, including those that are hard as well those that are soft. The sensor
      system is comprised of four sensing elements forming a tactile array integrated
      with the tip of a finger. We investigate the design configuration of a separate
      force sensing element with the aim to improve its measurement range. The force
      measurement of a single tactile element is based on a two-level displacement that
      is achieved thanks to a hybrid sensing structure made up of a stiff linear and
      flexible ortho-planar spring. An important outcome of this paper is a miniature
      tactile fingertip sensor that is capable of perceiving light contact, typically
      occurring during the initial stages of a grasp, as well as measuring higher
      forces, commonly present during tight grasps.

PMID- 29027921
TI  - Binding Direction-Based Two-Dimensional Flattened Contact Area Computing
      Algorithm for Protein-Protein Interactions.
AB  - Interactions between protein molecules are essential for the assembly, function,
      and regulation of proteins. The contact region between two protein molecules in a
      protein complex is usually complementary in shape for both molecules and the area
      of the contact region can be used to estimate the binding strength between two
      molecules. Although the area is a value calculated from the three-dimensional
      surface, it cannot represent the three-dimensional shape of the surface.
      Therefore, we propose an original concept of two-dimensional contact area which
      provides further information such as the ruggedness of the contact region. We
      present a novel algorithm for calculating the binding direction between two
      molecules in a protein complex, and then suggest a method to compute the two
      dimensional flattened area of the contact region between two molecules based on
      the binding direction.

PMID- 29027919
TI  - Shiga Toxins Induce Apoptosis and ER Stress in Human Retinal Pigment Epithelial
      Cells.
AB  - Shiga toxins (Stxs) produced by Shiga toxin-producing bacteria Shigella
      dysenteriae serotype 1 and select serotypes of Escherichia coli are the most
      potent known virulence factors in the pathogenesis of hemorrhagic colitis
      progressing to potentially fatal systemic complications such as acute renal
      failure, blindness and neurological abnormalities. Although numerous studies have
      defined apoptotic responses to Shiga toxin type 1 (Stx1) or Shiga toxin type 2
      (Stx2) in a variety of cell types, the potential significance of Stx-induced
      apoptosis of photoreceptor and pigmented cells of the eye following intoxication
      is unknown. We explored the use of immortalized human retinal pigment epithelial
      (RPE) cells as an in vitro model of Stx-induced retinal damage. To the best of
      our knowledge, this study is the first report that intoxication of RPE cells with
      Stxs activates both apoptotic cell death signaling and the endoplasmic reticulum
      (ER) stress response. Using live-cell imaging analysis, fluorescently labeled
      Stx1 or Stx2 were internalized and routed to the RPE cell endoplasmic reticulum.
      RPE cells were significantly sensitive to wild type Stxs by 72 h, while the cells
      survived challenge with enzymatically deficient mutant toxins (Stx1A- or Stx2A-).
      Upon exposure to purified Stxs, RPE cells showed activation of a caspase
      dependent apoptotic program involving a reduction of mitochondrial transmembrane
      potential (Deltapsim), increased activation of ER stress sensors IRE1, PERK and
      ATF6, and overexpression CHOP and DR5. Finally, we demonstrated that treatment of
      RPE cells with Stxs resulted in the activation of c-Jun N-terminal kinase (JNK)
      and p38 mitogen-activated protein kinase (p38MAPK), suggesting that the ribotoxic
      stress response may be triggered. Collectively, these data support the
      involvement of Stx-induced apoptosis in ocular complications of intoxication. The
      evaluation of apoptotic responses to Stxs by cells isolated from multiple organs
      may reveal unique functional patterns of the cytotoxic actions of these toxins in
      the systemic complications that follow ingestion of toxin-producing bacteria.

PMID- 29027922
TI  - The Detection of Water Flow in Rectangular Microchannels by Terahertz Time Domain
      Spectroscopy.
AB  - Flow characteristics of water were tested in a rectangular microchannel for
      Reynolds number (Re) between 0 and 446 by terahertz time domain spectroscopy (THz
      TDS). Output THz peak trough intensities and the calculated absorbances of the
      flow were analyzed theoretically. The results show a rapid change for Re < 250
      and a slow change as Re increases, which is caused by the early transition from
      laminar to transition flow beginning nearly at Re = 250. Then this finding is
      confirmed in the plot of the flow resistant. Our results demonstrate that the THz
      TDS could be a valuable tool to monitor and character the flow performance in
      microscale structures.

PMID- 29027923
TI  - Plasmonic Nanomaterial-Based Optical Biosensing Platforms for Virus Detection.
AB  - Plasmonic nanomaterials (P-NM) are receiving attention due to their excellent
      properties, which include surface-enhanced Raman scattering (SERS), localized
      surface plasmon resonance (LSPR) effects, plasmonic resonance energy transfer
      (PRET), and magneto optical (MO) effects. To obtain such plasmonic properties,
      many nanomaterials have been developed, including metal nanoparticles (MNP),
      bimetallic nanoparticles (bMNP), MNP-decorated carbon nanotubes, (MNP-CNT), and
      MNP-modified graphene (MNP-GRP). These P-NMs may eventually be applied to optical
      biosensing systems due to their unique properties. Here, probe biomolecules, such
      as antibodies (Ab), probe DNA, and probe aptamers, were modified on the surface
      of plasmonic materials by chemical conjugation and thiol chemistry. The optical
      property change in the plasmonic nanomaterials was monitored based on the
      interaction between the probe biomolecules and target virus. After
      bioconjugation, several optical properties, including fluorescence, plasmonic
      absorbance, and diffraction angle, were changed to detect the target
      biomolecules. This review describes several P-NMs as potential candidates of
      optical sensing platforms and introduces various applications in the optical
      biosensing field.

PMID- 29027925
TI  - Multiscale Modeling of Polycrystalline NiTi Shape Memory Alloy under Various
      Plastic Deformation Conditions by Coupling Microstructure Evolution and
      Macroscopic Mechanical Response.
AB  - Numerical modeling of microstructure evolution in various regions during uniaxial
      compression and canning compression of NiTi shape memory alloy (SMA) are studied
      through combined macroscopic and microscopic finite element simulation in order
      to investigate plastic deformation of NiTi SMA at 400  degrees C. In this
      approach, the macroscale material behavior is modeled with a relatively coarse
      finite element mesh, and then the corresponding deformation history in some
      selected regions in this mesh is extracted by the sub-model technique of finite
      element code ABAQUS and subsequently used as boundary conditions for the
      microscale simulation by means of crystal plasticity finite element method
      (CPFEM). Simulation results show that NiTi SMA exhibits an inhomogeneous plastic
      deformation at the microscale. Moreover, regions that suffered canning
      compression sustain more homogeneous plastic deformation by comparison with the
      corresponding regions subjected to uniaxial compression. The mitigation of
      inhomogeneous plastic deformation contributes to reducing the statistically
      stored dislocation (SSD) density in polycrystalline aggregation and also to
      reducing the difference of stress level in various regions of deformed NiTi SMA
      sample, and therefore sustaining large plastic deformation in the canning
      compression process.

PMID- 29027926
TI  - Nanocomposites for Machining Tools.
AB  - Machining tools are used in many areas of production. To a considerable extent,
      the performance characteristics of the tools determine the quality and cost of
      obtained products. The main materials used for producing machining tools are
      steel, cemented carbides, ceramics and superhard materials. A promising way to
      improve the performance characteristics of these materials is to design new
      nanocomposites based on them. The application of micromechanical modeling during
      the elaboration of composite materials for machining tools can reduce the
      financial and time costs for development of new tools, with enhanced performance.
      This article reviews the main groups of nanocomposites for machining tools and
      their performance.

PMID- 29027924
TI  - Anti-Salmonella Activity Modulation of Mastoparan V1-A Wasp Venom Toxin-Using
      Protease Inhibitors, and Its Efficient Production via an Escherichia coli
      Secretion System.
AB  - A previous study highlighted that mastoparan V1 (MP-V1), a mastoparan from the
      venom of the social wasp Vespula vulgaris, is a potent antimicrobial peptide
      against Salmonella infection, which causes enteric diseases. However, there exist
      some limits for its practical application due to the loss of its activity in an
      increased bacterial density and the difficulty of its efficient production. In
      this study, we first modulated successfully the antimicrobial activity of
      synthetic MP-V1 against an increased Salmonella population using protease
      inhibitors, and developed an Escherichia coli secretion system efficiently
      producing active MP-V1. The protease inhibitors used, except pepstatin A,
      significantly increased the antimicrobial activity of the synthetic MP-V1 at
      minimum inhibitory concentrations (determined against 106 cfu/mL of population)
      against an increased population (108 cfu/mL) of three different Salmonella
      serotypes, Gallinarum, Typhimurium and Enteritidis. Meanwhile, the E. coli strain
      harboring OmpA SS::MP-V1 was identified to successfully secrete active MP-V1 into
      cell-free supernatant, whose antimicrobial activity disappeared in the increased
      population (108 cfu/mL) of Salmonella Typhimurium recovered by adding a protease
      inhibitor cocktail. Therefore, it has been concluded that our challenge using the
      E. coli secretion system with the protease inhibitors is an attractive strategy
      for practical application of peptide toxins, such as MP-V1.

PMID- 29027927
TI  - Conotoxins as Tools to Understand the Physiological Function of Voltage-Gated
      Calcium (CaV) Channels.
AB  - Voltage-gated calcium (CaV) channels are widely expressed and are essential for
      the completion of multiple physiological processes. Close regulation of their
      activity by specific inhibitors and agonists become fundamental to understand
      their role in cellular homeostasis as well as in human tissues and organs. CaV
      channels are divided into two groups depending on the membrane potential required
      to activate them: High-voltage activated (HVA, CaV1.1-1.4; CaV2.1-2.3) and Low
      voltage activated (LVA, CaV3.1-3.3). HVA channels are highly expressed in brain
      (neurons), heart, and adrenal medulla (chromaffin cells), among others, and are
      also classified into subtypes which can be distinguished using pharmacological
      approaches. Cone snails are marine gastropods that capture their prey by
      injecting venom, "conopeptides", which cause paralysis in a few seconds. A subset
      of conopeptides called conotoxins are relatively small polypeptides, rich in
      disulfide bonds, that target ion channels, transporters and receptors localized
      at the neuromuscular system of the animal target. In this review, we describe the
      structure and properties of conotoxins that selectively block HVA calcium
      channels. We compare their potency on several HVA channel subtypes, emphasizing
      neuronal calcium channels. Lastly, we analyze recent advances in the therapeutic
      use of conotoxins for medical treatments.

PMID- 29027928
TI  - Automated Epileptic Seizure Detection Based on Wearable ECG and PPG in a Hospital
      Environment.
AB  - Electrocardiography has added value to automatically detect seizures in temporal
      lobe epilepsy (TLE) patients. The wired hospital system is not suited for a long
      term seizure detection system at home. To address this need, the performance of
      two wearable devices, based on electrocardiography (ECG) and photoplethysmography
      (PPG), are compared with hospital ECG using an existing seizure detection
      algorithm. This algorithm classifies the seizures on the basis of heart rate
      features, extracted from the heart rate increase. The algorithm was applied to
      recordings of 11 patients in a hospital setting with 701 h capturing 47 (fronto
      )temporal lobe seizures. The sensitivities of the hospital system, the wearable
      ECG device and the wearable PPG device were respectively 57%, 70% and 32%, with
      corresponding false alarms per hour of 1.92, 2.11 and 1.80. Whereas seizure
      detection performance using the wrist-worn PPG device was considerably lower, the
      performance using the wearable ECG is proven to be similar to that of the
      hospital ECG.

PMID- 29027930
TI  - Bioactive Coating with Two-Layer Hierarchy of Relief Obtained by Sol-Gel Method
      with Shock Drying and Osteoblast Response of Its Structure.
AB  - In this work, we analyze the efficiency of the modification of the implant
      surface. This modification was reached by the formation of a two-level relief
      hierarchy by means of a sol-gel approach that included dip coating with
      subsequent shock drying. Using this method, we fabricated a nanoporous layer with
      micron-sized defects on the nanotitanium surface. The present work continues an
      earlier study by our group, wherein the effect of osteoblast-like cell adhesion
      acceleration was found. In the present paper, we give the results of more
      detailed evaluation of coating efficiency. Specifically, cytological analysis was
      performed that included the study of the marker levels of osteoblast-like cell
      differentiation. We found a significant increase in the activity of alkaline
      phosphatase at the initial incubation stage. This is very important for
      implantation, since such an effect assists the decrease in the induction time of
      implant engraftment. Moreover, osteopontin expression remains high for long
      expositions. This indicates a prolonged osteogenic effect in the coating. The
      results suggest the acceleration of the pre-implant area mineralization and,
      correspondingly, the potential use of the developed coatings for bone
      implantation.

PMID- 29027929
TI  - Procyanidin B2 Protects Neurons from Oxidative, Nitrosative, and Excitotoxic
      Stress.
AB  - The aberrant generation of oxygen and nitrogen free radicals can cause severe
      damage to key cellular components, resulting in cell apoptosis. Similarly,
      excitotoxicity leads to protease activation and mitochondrial dysfunction, which
      subsequently causes cell death. Each of these factors play critical roles in the
      neuronal cell death underlying various neurodegenerative diseases. Procyanidin B2
      (PB2) is a naturally occurring polyphenolic compound found in high concentrations
      in cocoa, apples, and grapes. Here, we examine the neuroprotective effects of PB2
      in primary cultures of rat cerebellar granule neurons (CGNs) exposed to various
      stressors. CGNs were pre-incubated with PB2 and then neuronal stress was induced
      as described below. Mitochondrial oxidative stress was triggered with HA14-1, an
      inhibitor of the pro-survival Bcl-2 protein which induces glutathione-sensitive
      apoptosis. Glutamate and glycine were used to induce excitotoxicity. Sodium
      nitroprusside, a nitric oxide generating compound, was used to induce nitrosative
      stress. We observed significant dose-dependent protection of CGNs with PB2 for
      all of the above insults, with the greatest neuroprotective effect being observed
      under conditions of nitrosative stress. Intriguingly, the neuroprotective effect
      of PB2 against nitric oxide was superoxide-dependent, as we have recently shown
      for other catechol antioxidants. Finally, we induced neuronal stress through the
      removal of depolarizing extracellular potassium and serum (5K conditions), which
      is a classical model of intrinsic apoptosis in CGNs. PB2 did not display any
      significant protection against 5K-induced apoptosis at any concentration tested.
      We conclude that PB2 offers neuronal protection principally as an antioxidant by
      scavenging reactive oxygen and nitrogen species instead of through modulation of
      pro-survival cell signaling pathways. These findings suggest that PB2 may be an
      effective neuroprotective agent for the treatment of neurodegenerative disorders.

PMID- 29027931
TI  - Discovering the Biological Target of 5-epi-Sinuleptolide Using a Combination of
      Proteomic Approaches.
AB  - Sinuleptolide and its congeners are diterpenes with a norcembranoid skeleton
      isolated from the soft coral genus Sinularia. These marine metabolites are
      endowed with relevant biological activities, mainly associated with cancer
      development. 5-epi-sinuleptolide has been selected as a candidate for target
      discovery studies through the application of complementary proteomic approaches.
      Specifically, a combination of conventional chemical proteomics based on affinity
      chromatography, coupled with high-resolution mass spectrometry and
      bioinformatics, as well as drug affinity responsive target stability (DARTS), led
      to a clear identification of actins as main targets for 5-epi-sinuleptolide.
      Subsequent in-cell assays, performed with cytochalasin D as reference compound,
      gave information on the ability of 5-epi-sinuleptolide to disrupt the actin
      cytoskeleton by loss of actin fibers and formation of F-actin amorphous
      aggregates. These results suggest the potential application of 5-epi
      sinuleptolide as a useful tool in the study of the molecular processes impaired
      in several disorders in which actin is thought to play an essential role.

PMID- 29027932
TI  - Peer Victimization among Classmates-Associations with Students' Internalizing
      Problems, Self-Esteem, and Life Satisfaction.
AB  - Bullying is a major problem in schools and a large number of studies have
      demonstrated that victims have a high excess risk of poor mental health. It may
      however also affect those who are not directly victimized by peers. The present
      study investigates whether peer victimization among classmates is linked to
      internalizing problems, self-esteem, and life satisfaction at the individual
      level, when the student's own victimization has been taken into account. The data
      were derived from the first wave of the Swedish part of Youth in Europe Study
      (YES!), including information on 4319 students in grade 8 (14-15 years of age)
      distributed across 242 classes. Results from multilevel analyses show a
      significant association between classes with a high proportion of students being
      victimized and higher levels of internalizing problems, lower self-esteem, and
      lower life satisfaction at the student level. This association holds when the
      student's own victimization has been taken into account. This suggests that peer
      victimization negatively affects those who are directly exposed, as well as their
      classmates. We conclude that efficient methods and interventions to reduce
      bullying in school are likely to benefit not only those who are victimized, but
      all students.

PMID- 29027933
TI  - DPPH Radical Scavenging and Postprandial Hyperglycemia Inhibition Activities and
      Flavonoid Composition Analysis of Hawk Tea by UPLC-DAD and UPLC-Q/TOF MSE.
AB  - Hawk tea (Litsea coreana Levl. var. Lanuginosa (Migo) Yen C. Yang & P.H. Huang),
      a very popular herbal tea material, has attracted more and more attention due to
      its high antioxidant properties and possible therapeutic effect on type II
      diabetes mellitus. The raw materials of Hawk tea are usually divided into three
      kinds: bud tea (BT), primary leaf tea (PLT) and mature leaf tea (MLT). In this
      study, the DPPH radical scavenging activity and the antimicrobial properties of
      these three kinds of Hawk tea from different regions were comparatively
      investigated, and a ultra-high performance liquid chromatographic coupled with a
      photodiode array detector (UPLC-DAD) method was employed for comparison of the
      three major flavonoid constituents, including hyperoside, isoquercitrin and
      astragalin, in different samples of Hawk tea. At the same time, the effect of
      methanol extract (ME) of PLT on the mouse postprandial blood glucose and the
      effect of ME and its different fractions (petroleum ether fraction (PE), ethyl
      acetate fraction (EA), n-butanol fraction (n-BuOH), and water fraction (WF)) on
      the activity of alpha-glucosidase were studied. The results showed that Hawk BT
      and Hawk PLT possessed the higher radicals scavenging activity than Hawk MLT,
      while the antibacterial activity against P. vulgaris of PLT and MLT was higher
      than Hawk BT. The contents of the three major flavonoid constituents in samples
      of Hawk PLT are higher than Hawk BT and Hawk MLT. The mouse postprandial blood
      glucose levels of the middle dose (0.5 g/kg) group and the high dose (1 g/kg)
      group with oral administration of the ME of PLT were significantly lower than the
      control group. What's more, the inhibitory effect of ME of PLT and its EA and n
      BuOH fractions on alpha-glucosidase was significantly higher than that of
      acarbose. Rapid ultra-high performance liquid chromatography/quadrupole time-of
      flight-mass spectrometry (UPLC-ESI-QTOF-MS) was used to identify the flavonoids
      in Hawk PLT, and a total of 20 flavonoids were identified or tentatively
      identified by comparing their retention times and accurate mass measurements with
      reference compounds or literature data. The bioactive flavonoid composition and
      DPPH radical scavenging activities present in different Hawk tea raw materials
      are quite different due to the different ontogenesis of these raw materials.
      Further studies on PLT showed that the substances in PLT ME could reduce the
      level of mouse postprandial blood glucose through inhibiting the activity of
      alpha-glucosidase.

PMID- 29027935
TI  - Robust Stereo Visual Odometry Using Improved RANSAC-Based Methods for Mobile
      Robot Localization.
AB  - In this paper, we present a novel approach for stereo visual odometry with robust
      motion estimation that is faster and more accurate than standard RANSAC (Random
      Sample Consensus). Our method makes improvements in RANSAC in three aspects:
      first, the hypotheses are preferentially generated by sampling the input feature
      points on the order of ages and similarities of the features; second, the
      evaluation of hypotheses is performed based on the SPRT (Sequential Probability
      Ratio Test) that makes bad hypotheses discarded very fast without verifying all
      the data points; third, we aggregate the three best hypotheses to get the final
      estimation instead of only selecting the best hypothesis. The first two aspects
      improve the speed of RANSAC by generating good hypotheses and discarding bad
      hypotheses in advance, respectively. The last aspect improves the accuracy of
      motion estimation. Our method was evaluated in the KITTI (Karlsruhe Institute of
      Technology and Toyota Technological Institute) and the New Tsukuba dataset.
      Experimental results show that the proposed method achieves better results for
      both speed and accuracy than RANSAC.

PMID- 29027934
TI  - Angiotensin I-Converting Enzyme (ACE) Inhibitory Activity, Antioxidant
      Properties, Phenolic Content and Amino Acid Profiles of Fucus spiralis L. Protein
      Hydrolysate Fractions.
AB  - Food protein-derived hydrolysates with multi-bioactivities such as
      antihypertensive and antioxidant properties have recently received special
      attention since both activities can play significant roles in preventing
      cardiovascular diseases. This study reports, for the first time, the angiotensin
      I-converting enzyme (ACE)-inhibition and antioxidant properties of ultrafiltrate
      fractions (UF) with different molecular weight ranges (<1, 1-3 and >=3 kDa)
      obtained from Fucus spiralis protein hydrolysate (FSPH) digested with cellulase
      bromelain. The amino acids profile, recovery yield, protein, peptide and total
      phenolic contents of these FSPH-UF, and the in vitro digestibility of F. spiralis
      crude protein were also investigated. FSPH-UF >=3 kDa presented remarkably higher
      ACE-inhibition, yield, peptide and polyphenolic (phlorotannins) contents.
      Antioxidant analysis showed that FSPH-UF <1 kDa and >=3 kDa exhibited
      significantly higher scavenging of 2,2-diphenyl-1-picrylhydrazyl radical and
      ferrous ion-chelating (FIC) activity. FSPH-UF >=3 kDa had also notably higher
      ferric reducing antioxidant power (FRAP). Strong correlations were observed
      between ACE-inhibition and antioxidant activities (FIC and FRAP). The results
      suggest that ACE-inhibition and antioxidant properties of FSPH-UF may be due to
      the bioactive peptides and polyphenols released during the enzymatic hydrolysis.
      In conclusion, this study shows the potential use of defined size FSPH-UF for the
      prevention/treatment of hypertension and/or oxidative stress-related diseases.

PMID- 29027936
TI  - Assessing White Wine Viscosity Variation Using Polarized Laser Speckle: A
      Promising Alternative to Wine Sensory Analysis.
AB  - In this paper, we report measurements of wine viscosity, correlated to polarized
      laser speckle results. Experiments were performed on white wine samples produced
      with a single grape variety. Effects of the wine making cellar, the grape
      variety, and the vintage on wine Brix degree, alcohol content, viscosity, and
      speckle parameters are considered. We show that speckle parameters, namely,
      spatial contrast and speckle decorrelation time, as well as the inertia moment
      extracted from the temporal history speckle pattern, are mainly affected by the
      alcohol and sugar content and hence the wine viscosity. Principal component
      analysis revealed a high correlation between laser speckle results on the one
      hand and viscosity and Brix degree values on the other. As speckle analysis
      proved to be an efficient method of measuring the variation of the viscosity of
      white mono-variety wine, one can therefore consider it as an alternative method
      to wine sensory analysis.

PMID- 29027937
TI  - Abrin Toxicity and Bioavailability after Temperature and pH Treatment.
AB  - Abrin, one of most potent toxins known to man, is derived from the rosary pea
      (jequirity pea), Abrus precatorius and is a potential bioterror weapon. The
      temperature and pH stability of abrin was evaluated with an in vitro cell free
      translation (CFT) assay, a Vero cell culture cytotoxicity assay, and an in vivo
      mouse bioassay. pH treatment of abrin had no detrimental effect on its stability
      and toxicity as seen either in vitro or in vivo. Abrin exposure to increasing
      temperatures did not completely abrogate protein translation. In both the cell
      culture cytotoxicity model and the mouse bioassay, abrin's toxic effects were
      completely abrogated if the toxin was exposed to temperatures of 74  degrees C or
      higher. In the cell culture model, 63  degrees C-treated abrin had a 30%
      reduction in cytotoxicity which was validated in the in vivo mouse bioassay with
      all mice dying but with a slight time-to-death delay as compared to the non
      treated abrin control. Since temperature inactivation did not affect abrin's
      ability to inhibit protein synthesis (A-chain), we hypothesize that high
      temperature treatment affected abrin's ability to bind to cellular receptors
      (affecting B-chain). Our results confirm the absolute need to validate in vitro
      cytotoxicity assays with in vivo mouse bioassays.

PMID- 29027938
TI  - Palladium Nanoparticles-Based Fluorescence Resonance Energy Transfer Aptasensor
      for Highly Sensitive Detection of Aflatoxin M1 in Milk.
AB  - A highly sensitive aptasensor for aflatoxin M1 (AFM1) detection was constructed
      based on fluorescence resonance energy transfer (FRET) between 5
      carboxyfluorescein (FAM) and palladium nanoparticles (PdNPs). PdNPs (33 nm) were
      synthesized through a seed-mediated growth method and exhibited broad and strong
      absorption in the whole ultraviolet-visible (UV-Vis) range. The strong
      coordination interaction between nitrogen functional groups of the AFM1 aptamer
      and PdNPs brought FAM and PdNPs in close proximity, which resulted in the
      fluorescence quenching of FAM to a maximum extent of 95%. The non-specific
      fluorescence quenching caused by PdNPs towards fluorescein was negligible. After
      the introduction of AFM1 into the FAM-AFM1 aptamer-PdNPs FRET system, the AFM1
      aptamer preferentially combined with AFM1 accompanied by conformational change,
      which greatly weakened the coordination interaction between the AFM1 aptamer and
      PdNPs. Thus, fluorescence recovery of FAM was observed and a linear relationship
      between the fluorescence recovery and the concentration of AFM1 was obtained in
      the range of 5-150 pg/mL in aqueous buffer with the detection limit of 1.5 pg/mL.
      AFM1 detection was also realized in milk samples with a linear detection range
      from 6 pg/mL to 150 pg/mL. The highly sensitive FRET aptasensor with simple
      configuration shows promising prospect in detecting a variety of food
      contaminants.

PMID- 29027939
TI  - Nicotine Component of Cigarette Smoke Extract (CSE) Decreases the Cytotoxicity of
      CSE in BEAS-2B Cells Stably Expressing Human Cytochrome P450 2A13.
AB  - Cytochrome P450 2A13 (CYP2A13), an extrahepatic enzyme mainly expressed in the
      human respiratory system, has been reported to mediate the metabolism and
      toxicity of cigarette smoke. We previously found that nicotine inhibited 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism by CYP2A13, but its
      influence on other components of cigarette smoke remains unclear. The nicotine
      component of cigarette smoke extract (CSE) was separated, purified, and
      identified using high-performance liquid chromatography (HPLC) and ultra
      performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS),
      splitting CSE into a nicotine section (CSE-N) and nicotine-free section (CSE-O).
      Cell viability and apoptosis by Cell Counting Kit-8 (CCK-8) and flow cytometry
      assays were conducted on immortalized human bronchial epithelial (BEAS-2B) cells
      stably expressing CYP2A13 (B-2A13) or vector (B-V), respectively. Interestingly,
      CSE and CSE-O were toxic to BEAS-2B cells whereas CSE-N showed less cytotoxicity.
      CSE-O was more toxic to B-2A13 cells than to B-V cells (IC50 of 2.49% vs. 7.06%),
      which was flatted by 8-methoxypsoralen (8-MOP), a CYP inhibitor. CSE-O rather
      than CSE or CSE-N increased apoptosis of B-2A13 cells rather than B-V cells.
      Accordingly, compared to CSE-N and CSE, CSE-O significantly changed the
      expression of three pairs of pro- and anti-apoptotic proteins, Bcl-2 Associated X
      Protein/B cell lymphoma-2 (Bax/Bcl-2), Cleaved Poly (Adenosine Diphosphate
      Ribose) Polymerase/Poly (Adenosine Diphosphate-Ribose) Polymerase (C-PARP/PARP),
      and C-caspase-3/caspase-3, in B-2A13 cells. In addition, recombination of CSE-N
      and CSE-O (CSE-O/N) showed similar cytotoxicity and apoptosis to the original
      CSE. These results demonstrate that the nicotine component decreases the
      metabolic activation of CYP2A13 to CSE and aids in understanding the critical
      role of CYP2A13 in human respiratory diseases caused by cigarette smoking.

PMID- 29027940
TI  - Zika Virus Persistently and Productively Infects Primary Adult Sensory Neurons In
      Vitro.
AB  - Zika virus (ZIKV) has recently surged in human populations, causing an increase
      in congenital and Guillain-Barre syndromes. While sexual transmission and
      presence of ZIKV in urine, semen, vaginal secretions, and saliva have been
      established, the origin of persistent virus shedding into biological secretions
      is not clear. Using a primary adult murine neuronal culture model, we have
      determined that ZIKV persistently and productively infects sensory neurons of the
      trigeminal and dorsal root ganglia, which innervate glands and mucosa of the face
      and the genitourinary tract, respectively, without apparent injury. Autonomic
      neurons that innervate these regions are not permissive for infection. However,
      productive ZIKV infection of satellite glial cells that surround and support
      sensory and autonomic neurons in peripheral ganglia results in their destruction.
      Persistent infection of sensory neurons, without affecting their viability,
      provides a potential reservoir for viral shedding in biological secretions for
      extended periods of time after infection. Furthermore, viral destruction of
      satellite glial cells may contribute to the development of Guillain-Barre
      Syndrome via an alternative mechanism to the established autoimmune response.

PMID- 29027941
TI  - Verification of a Method for Measuring Parkinson's Disease Related Temporal
      Irregularity in Spiral Drawings.
AB  - Parkinson's disease (PD) is a progressive movement disorder caused by the death
      of dopamine-producing cells in the midbrain. There is a need for frequent symptom
      assessment, since the treatment needs to be individualized as the disease
      progresses. The aim of this paper was to verify and further investigate the
      clinimetric properties of an entropy-based method for measuring PD-related upper
      limb temporal irregularities during spiral drawing tasks. More specifically,
      properties of a temporal irregularity score (TIS) for patients at different
      stages of PD, and medication time points were investigated. Nineteen PD patients
      and 22 healthy controls performed repeated spiral drawing tasks on a smartphone.
      Patients performed the tests before a single levodopa dose and at specific time
      intervals after the dose was given. Three movement disorder specialists rated
      videos of the patients based on the unified PD rating scale (UPDRS) and the
      Dyskinesia scale. Differences in mean TIS between the groups of patients and
      healthy subjects were assessed. Test-retest reliability of the TIS was measured.
      The ability of TIS to detect changes from baseline (before medication) to later
      time points was investigated. Correlations between TIS and clinical rating scores
      were assessed. The mean TIS was significantly different between healthy subjects
      and patients in advanced groups (p-value = 0.02). Test-retest reliability of TIS
      was good with Intra-class Correlation Coefficient of 0.81. When assessing changes
      in relation to treatment, TIS contained some information to capture changes from
      Off to On and wearing off effects. However, the correlations between TIS and
      clinical scores (UPDRS and Dyskinesia) were weak. TIS was able to differentiate
      spiral drawings drawn by patients in an advanced stage from those drawn by
      healthy subjects, and TIS had good test-retest reliability. TIS was somewhat
      responsive to single-dose levodopa treatment. Since TIS is an upper limb high
      frequency-based measure, it cannot be detected during clinical assessment.

PMID- 29027942
TI  - On the Effect of Hydrogen on the Low-Temperature Elastic and Anelastic Properties
      of Ni-Ti-Based Alloys.
AB  - Linear and non-linear internal friction and the effective Young's modulus of a
      Ni50.8Ti49.2 alloy have been studied after different heat treatments, affecting
      hydrogen content, over wide ranges of temperatures (13-300 K) and strain
      amplitudes (10-7-10-4) at frequencies near 90 kHz. It has been shown that the
      contamination of the alloy by hydrogen strongly affects the internal friction and
      Young's modulus of the martensitic phase. Presence of hydrogen gives rise to a
      non-relaxation internal friction maximum due to a competition of two different
      temperature-dependent processes. The temperature position and height of the
      maximum depend strongly on the hydrogen content. We conclude that many of the
      internal friction peaks, reported earlier for differently treated Ni-Ti-based
      alloys, had the same origin as the present maximum.

PMID- 29027943
TI  - Low-Grade Dysplastic Nodules Revealed as the Tipping Point during Multistep
      Hepatocarcinogenesis by Dynamic Network Biomarkers.
AB  - Hepatocellular carcinoma (HCC) is a complex disease with a multi-step
      carcinogenic process from preneoplastic lesions, including cirrhosis, low-grade
      dysplastic nodules (LGDNs), and high-grade dysplastic nodules (HGDNs) to HCC.
      There is only an elemental understanding of its molecular pathogenesis, for which
      a key problem is to identify when and how the critical transition happens during
      the HCC initiation period at a molecular level. In this work, for the first time,
      we revealed that LGDNs is the tipping point (i.e., pre-HCC state rather than HCC
      state) of hepatocarcinogenesis based on a series of gene expression profiles by a
      new mathematical model termed dynamic network biomarkers (DNB)-a group of
      dominant genes or molecules for the transition. Different from the conventional
      biomarkers based on the differential expressions of the observed genes (or
      molecules) for diagnosing a disease state, the DNB model exploits collective
      fluctuations and correlations of the observed genes, thereby predicting the
      imminent disease state or diagnosing the critical state. Our results show that
      DNB composed of 59 genes signals the tipping point of HCC (i.e., LGDNs). On the
      other hand, there are a large number of differentially expressed genes between
      cirrhosis and HGDNs, which highlighted the stark differences or drastic changes
      before and after the tipping point or LGDNs, implying the 59 DNB members serving
      as the early-warning signals of the upcoming drastic deterioration for HCC. We
      further identified the biological pathways responsible for this transition, such
      as the type I interferon signaling pathway, Janus kinase-signal transducers and
      activators of transcription (JAK-STAT) signaling pathway, transforming growth
      factor (TGF)-beta signaling pathway, retinoic acid-inducible gene I (RIG-I)-like
      receptor signaling pathway, cell adhesion molecules, and cell cycle. In
      particular, pathways related to immune system reactions and cell adhesion were
      downregulated, and pathways related to cell growth and death were upregulated.
      Furthermore, DNB was validated as an effective predictor of prognosis for HCV
      induced HCC patients by survival analysis on independent data, suggesting a
      potential clinical application of DNB. This work provides biological insights
      into the dynamic regulations of the critical transitions during multistep
      hepatocarcinogenesis.

PMID- 29027944
TI  - The Fabrication and Characterization of Ni/4H-SiC Schottky Diode Radiation
      Detectors with a Sensitive Area of up to 4 cm2.
AB  - Silicon carbide (SiC) detectors of an Ni/4H-SiC Schottky diode structure and with
      sensitive areas of 1-4 cm2 were fabricated using high-quality lightly doped
      epitaxial 4H-SiC material, and were tested in the detection of alpha particles
      and pulsed X-rays/UV-light. A linear energy response to alpha particles ranging
      from 5.157 to 5.805 MeV was obtained. The detectors were proved to have a low
      dark current, a good energy resolution, and a high neutron/gamma discrimination
      for pulsed radiation, showing the advantages in charged particle detection and
      neutron detection in high-temperature and high-radiation environments.

PMID- 29027945
TI  - Etched Polymer Fibre Bragg Gratings and Their Biomedical Sensing Applications.
AB  - Bragg gratings in etched polymer fibres and their unique properties and
      characteristics are discussed in this paper. Due to the change in material and
      mechanical properties of the polymer fibre through etching, Bragg gratings
      inscribed in such fibres show high reflectivity and enhanced intrinsic
      sensitivity towards strain, temperature, and pressure. The short-term and long
      term stability of the gratings and the effect of hysteresis on the dynamic
      characteristics are also discussed. The unique properties and enhanced intrinsic
      sensitivity of etched polymer fibre Bragg grating are ideal for the development
      of high-sensitivity sensors for biomedical applications. To demonstrate their
      biomedical sensing capabilities, a high-sensitivity pressure transducer that
      operates in the blood pressure range, and a breathing rate monitoring device are
      developed and presented.

PMID- 29027946
TI  - Serum 25-Hydroxyvitamin D Concentrations and Indicators of Mental Health: An
      Analysis of the Canadian Health Measures Survey.
AB  - The main function of vitamin D is calcium homeostasis. However, emerging evidence
      has correlated adequate serum 25-hydroxyvitamin D (25(OH)D) concentrations with
      better mental health. The objective of this study is to investigate the
      association of serum 25(OH)D concentrations with indicators of mental health such
      as depression, anxiety, and stress. Associations of serum 25(OH)D concentrations
      with four indicators of mental health were examined using ordered logistic
      regression models with increasing specificity that account for demographics,
      socio-economic status, and health. Margin effects are used to determine the
      probability of the average adult Canadian being in the best mental health state
      by groupings of serum 25(OH)D concentrations. A robust association between serum
      25(OH)D concentrations and the indicators of mental health were observed. In the
      fully adjusted ordered logistic model, an average Canadian appeared more likely
      to experience better mental health when serum 25(OH)D concentrations were higher.
      This study adds to the weight of the existence of an association between vitamin
      D status and mental health, but, as this study is cross sectional, it does not
      establish causality. Due to the low risk of harm from toxicity and the relative
      modest costs of vitamin D supplements, more research to establish the
      effectiveness and causality of this relationship is recommended.

PMID- 29027947
TI  - Two New Sandwich-Type Polyoxomolybdates Functionalized with Diphosphonates:
      Efficient and Selective Oxidation of Sulfides to Sulfones.
AB  - Two sandwich-type polyoxomolybdates Na8[MO2{Mo2O5(O3PCH3C(O)PO3)}2] (M = Ni2+
      (1); Co2+ (2)) were synthesized by one-pot reaction of Na2HPMo12O40.14H2O, 1
      hydroxy ethidene diphosphonic acid (HEDP=HOC(CH3)(PO3H2)2), and (1) NiCl2/CoCl2
      (2). Compounds 1 and 2 were characterized by single crystal X-ray analysis, X-ray
      powder diffraction (XRPD), IR spectroscopy, 31P NMR spectra, UV-vis spectroscopy,
      and thermogravimetric analyses (TGA). Structural analysis reveals that 1 and 2
      exhibit similar centrosymmetric structure, which consists of one transition metal
      (TM) ion sandwiched by two same subunits {Mo2O5(O3PCH3C(O)PO3)}. The clusters 1
      and 2 show efficient catalytic activities for oxidation of thioanisole. Moreover,
      they are catalytically selective for oxidizing thioanisole. Both resuable
      polyoxomolybdates 1 and 2 catalysts show good thermo- and hydrolytic stability.
      It is noted that compound 1 shows outstanding catalytic activity for oxidation of
      various sulfides to corresponding sulfones with 93-100% selectivity at 97-100%
      conversion in one hour under mild conditions, which is potentially valuable to
      the removal of organic sulfides.

PMID- 29027949
TI  - The Flexural Strength and Fracture Toughness of TC4-Based Laminated Composites
      Reinforced with Ti Aluminide and Carbide.
AB  - TiC-Ti-Al mixed powders and TC4 titanium alloy foils were overlapped layer-by
      layer in the graphite die. The TC4-based laminated composite sheets reinforced by
      Ti aluminide and carbide were successfully fabricated via spark plasma sintering
      (SPS) at 1100  degrees C with a well-bonded interface. The composite layers were
      mainly composed of TiAl, Ti3Al, Ti2AlC, and Ti3AlC2 phases. The carbides
      particles distributed in the matrix played an important role in the deflection of
      cracks and the passivation of microcracks. TC4 titanium alloy layers had an
      obvious effect on the stress distribution during the loading process, and
      provided an energy dissipation mechanism, which could improve the mechanical
      properties of the laminated composite sheets obviously. When the theoretical
      amount of Ti2AlC was 20 wt %, the flexural strength and fracture toughness of the
      laminated composite sheets reached the maximum value in the arrester direction,
      which were 1428.79 MPa and 64.08 MPa.m1/2, respectively.

PMID- 29027948
TI  - Comparing the Performance of Indoor Localization Systems through the EvAAL
      Framework.
AB  - In recent years, indoor localization systems have been the object of significant
      research activity and of growing interest for their great expected social impact
      and their impressive business potential. Application areas include tracking and
      navigation, activity monitoring, personalized advertising, Active and Assisted
      Living (AAL), traceability, Internet of Things (IoT) networks, and Home-land
      Security. In spite of the numerous research advances and the great industrial
      interest, no canned solutions have yet been defined. The diversity and
      heterogeneity of applications, scenarios, sensor and user requirements, make it
      difficult to create uniform solutions. From that diverse reality, a main problem
      is derived that consists in the lack of a consensus both in terms of the metrics
      and the procedures used to measure the performance of the different indoor
      localization and navigation proposals. This paper introduces the general lines of
      the EvAAL benchmarking framework, which is aimed at a fair comparison of indoor
      positioning systems through a challenging competition under complex, realistic
      conditions. To evaluate the framework capabilities, we show how it was used in
      the 2016 Indoor Positioning and Indoor Navigation (IPIN) Competition. The 2016
      IPIN competition considered three different scenario dimensions, with a variety
      of use cases: (1) pedestrian versus robotic navigation, (2) smartphones versus
      custom hardware usage and (3) real-time positioning versus off-line post
      processing. A total of four competition tracks were evaluated under the same
      EvAAL benchmark framework in order to validate its potential to become a standard
      for evaluating indoor localization solutions. The experience gained during the
      competition and feedback from track organizers and competitors showed that the
      EvAAL framework is flexible enough to successfully fit the very different tracks
      and appears adequate to compare indoor positioning systems.

PMID- 29027950
TI  - Control Design and Digital Implementation of a Fast 2-Degree-of-Freedom
      Translational Optical Image Stabilizer for Image Sensors in Mobile Camera Phones.
AB  - This study presents design, digital implementation and performance validation of
      a lead-lag controller for a 2-degree-of-freedom (DOF) translational optical image
      stabilizer (OIS) installed with a digital image sensor in mobile camera phones.
      Nowadays, OIS is an important feature of modern commercial mobile camera phones,
      which aims to mechanically reduce the image blur caused by hand shaking while
      shooting photos. The OIS developed in this study is able to move the imaging lens
      by actuating its voice coil motors (VCMs) at the required speed to the position
      that significantly compensates for imaging blurs by hand shaking. The
      compensation proposed is made possible by first establishing the exact, nonlinear
      equations of motion (EOMs) for the OIS, which is followed by designing a simple
      lead-lag controller based on established nonlinear EOMs for simple digital
      computation via a field-programmable gate array (FPGA) board in order to achieve
      fast response. Finally, experimental validation is conducted to show the
      favorable performance of the designed OIS; i.e., it is able to stabilize the lens
      holder to the desired position within 0.02 s, which is much less than previously
      reported times of around 0.1 s. Also, the resulting residual vibration is less
      than 2.2-2.5 MUm, which is commensurate to the very small pixel size found in
      most of commercial image sensors; thus, significantly minimizing image blur
      caused by hand shaking.

PMID- 29027952
TI  - Modeling and Compensation of Random Drift of MEMS Gyroscopes Based on Least
      Squares Support Vector Machine Optimized by Chaotic Particle Swarm Optimization.
AB  - MEMS (Micro Electro Mechanical System) gyroscopes have been widely applied to
      various fields, but MEMS gyroscope random drift has nonlinear and non-stationary
      characteristics. It has attracted much attention to model and compensate the
      random drift because it can improve the precision of inertial devices. This paper
      has proposed to use wavelet filtering to reduce noise in the original data of
      MEMS gyroscopes, then reconstruct the random drift data with PSR (phase space
      reconstruction), and establish the model for the reconstructed data by LSSVM
      (least squares support vector machine), of which the parameters were optimized
      using CPSO (chaotic particle swarm optimization). Comparing the effect of
      modeling the MEMS gyroscope random drift with BP-ANN (back propagation artificial
      neural network) and the proposed method, the results showed that the latter had a
      better prediction accuracy. Using the compensation of three groups of MEMS
      gyroscope random drift data, the standard deviation of three groups of
      experimental data dropped from 0.00354 degrees /s, 0.00412 degrees /s, and
      0.00328 degrees /s to 0.00065 degrees /s, 0.00072 degrees /s and 0.00061 degrees
      /s, respectively, which demonstrated that the proposed method can reduce the
      influence of MEMS gyroscope random drift and verified the effectiveness of this
      method for modeling MEMS gyroscope random drift.

PMID- 29027951
TI  - Effects of Maternal Low-Energy Diet during Gestation on Intestinal Morphology,
      Disaccharidase Activity, and Immune Response to Lipopolysaccharide Challenge in
      Pig Offspring.
AB  - Maternal nutrition during gestation is involved in the offspring's intestinal
      development and immunity. The aim of this study was to (1) determine the effects
      of maternal energy on intestinal digestion and absorption function in offspring,
      using pigs as a model; and (2) to evaluate the potential effect and mechanisms of
      maternal energy in modulating immune responses of lipopolysaccharide (LPS)
      challenged piglets. After mating, thirty-six nine-parity sows (Landrace *
      Yorkshire), body weight (BW) (initial body weight 233.56 +/- 2.77 kg) were
      allocated to two dietary treatment groups; a control diet (CON) group and a low
      energy diet (LED) group. The nutrient levels of the CON were based on the
      nutrient recommendations by the National Research Council (NRC, 2012), and
      contained 3.40 MCal digestible energy (DE)/kg diet and 7.3% crude protein; while
      the LED contained 3.00 MCal DE/kg diet. The dietary treatments were introduced
      from day 1 of gestation to farrowing. Intestine samples were collected from the
      pigs' offspring at birth, and at weaning (day 28 post-birth). At weaning, male
      pigs from control and LED groups were intraperitoneally injected with LPS (50
      MUg/kg body weight) or saline (n = 6), and sacrificed at 4 h post-injection to
      collect blood, intestine and digesta samples for biochemical analysis. The
      results indicated that the maternal LED markedly decreased the BW, small
      intestinal weight, and the ratio of jejunum and ileum villus height to crypt
      depth in the offspring. Moreover, the activities of lactase and sucrase in
      newborn piglets' intestine, and sucrase and maltase in weaning piglet intestine
      were markedly decreased by the maternal LED. In addition, maternal LED
      significantly increased the mRNA relative expression of ileal IL-6 and TNF-alpha
      in newborn piglets. Plasma IL-1beta concentration and colonic Escherichia coli
      amount were affected by maternal diet (p < 0.05) and LPS challenge (p < 0.001).
      Maternal LED significant increased the mRNA relative expression of ileal TLR-4,
      IL-1beta and NF-kappaB as well as decreased ZO-1 in weaning pigs after LPS
      challenge (p < 0.05). In conclusion, decreasing energy intake could suppress the
      offspring's intestinal digestion and absorption function, and increase the
      susceptibility of weaning piglets to LPS challenge.

PMID- 29027953
TI  - Vitamin D and Age-Related Macular Degeneration.
AB  - In recent years, the relationship between vitamin D and health has received
      growing attention from the scientific and medical communities. Vitamin D
      deficiencies have been repeatedly associated with various acute and chronic
      diseases, including age-related macular degeneration (AMD). Its active
      metabolite, 1alpha,25-dihydoxy vitamin D, acts as a modulator of cell
      proliferation, differentiation and apoptosis, and cumulative data from
      experimental and observational studies suggest that relatively a lower vitamin D
      status could be a potential risk factor for the development of early and/or late
      AMD. Herein, we made a narrative review of the mechanisms linking a potential
      role of vitamin D with the current concepts of AMD pathophysiology.

PMID- 29027955
TI  - 3D Defect Localization on Exothermic Faults within Multi-Layered Structures Using
      Lock-In Thermography: An Experimental and Numerical Approach.
AB  - Micro-electronic devices are increasingly incorporating miniature multi-layered
      integrated architectures. However, the localization of faults in three
      dimensional structure remains challenging. This study involved the experimental
      and numerical estimation of the depth of a thermally active heating source buried
      in multi-layered silicon wafer architecture by using both phase information from
      an infrared microscopy and finite element simulation. Infrared images were
      acquired and real-time processed by a lock-in method. It is well known that the
      lock-in method can increasingly improve detection performance by enhancing the
      spatial and thermal resolution of measurements. Operational principle of the lock
      in method is discussed, and it is represented that phase shift of the thermal
      emission from a silicon wafer stacked heat source chip (SSHSC) specimen can
      provide good metrics for the depth of the heat source buried in SSHSCs. Depth was
      also estimated by analyzing the transient thermal responses using the coupled
      electro-thermal simulations. Furthermore, the effects of the volumetric heat
      source configuration mimicking the 3D through silicon via integration package
      were investigated. Both the infrared microscopic imaging with the lock-in method
      and FE simulation were potentially useful for 3D isolation of exothermic faults
      and their depth estimation for multi-layered structures, especially in packaged
      semiconductors.

PMID- 29027956
TI  - Combined Venom Gland Transcriptomic and Venom Peptidomic Analysis of the
      Predatory Ant Odontomachus monticola.
AB  - Ants (hymenoptera: Formicidae) have adapted to many different environments and
      have become some of the most prolific and successful insects. To date, 13,258 ant
      species have been reported. They have been classified into 333 genera and 17
      subfamilies. Except for a few Formicinae, Dolichoderinae, and members of other
      subfamilies, most ant species have a sting with venom. The venoms are composed of
      formic acid, alkaloids, hydrocarbons, amines, peptides, and proteins. Unlike the
      venoms of other animals such as snakes and spiders, ant venoms have seldom been
      analyzed comprehensively, and their compositions are not yet completely known. In
      this study, we used both transcriptomic and peptidomic analyses to study the
      composition of the venom produced by the predatory ant species Odontomachus
      monticola. The transcriptome analysis yielded 49,639 contigs, of which 92 encoded
      toxin-like peptides and proteins with 18,106,338 mapped reads. We identified six
      pilosulin-like peptides by transcriptomic analysis in the venom gland. Further,
      we found intact pilosulin-like peptide 1 and truncated pilosulin-like peptides 2
      and 3 by peptidomic analysis in the venom. Our findings related to ant venom
      peptides and proteins may lead the way towards development and application of
      novel pharmaceutical and biopesticidal resources.

PMID- 29027957
TI  - Peroxisomal 2-Hydroxyacyl-CoA Lyase Is Involved in Endogenous Biosynthesis of
      Heptadecanoic Acid.
AB  - Circulating heptadecanoic acid (C17:0) is reported to be a pathology
      risk/prognosis biomarker and a dietary biomarker. This pathology relationship has
      been shown to be reliably predictive even when independent of dietary
      contributions, suggesting that the endogenous biosynthesis of C17:0 is related to
      the pathological aetiology. Little is known about C17:0 biosynthesis, which
      tissues contribute to the circulating levels, and how C17:0 is related to
      pathology. Hacl1+/- mice were mated to obtain Hacl1-/- and Hacl1+/+ control mice.
      At 14 weeks, they were anesthetized for tissue collection and fatty acid
      analysis. Compared to Hacl1+/+, C15:0 was not significantly affected in any Hacl1
      /- tissues. However, the Hacl1-/- plasma and liver C17:0 levels were
      significantly lower: ~26% and ~22%, respectively. No significant differences were
      seen in the different adipose tissues. To conclude, Hacl1 plays a significant
      role in the liver and plasma levels of C17:0, providing evidence it can be
      endogenously biosynthesized via alpha-oxidation. The strong inverse association
      of C17:0 with pathology raises the question whether there is a direct link
      between alpha-oxidation and these diseases. Currently, there is no clear
      evidence, warranting further research into the role of alpha-oxidation in
      relation to metabolic diseases.

PMID- 29027954
TI  - Marine Sponge Natural Products with Anticancer Potential: An Updated Review.
AB  - Despite the huge investment into research and the significant effort and advances
      made in the search for new anticancer drugs in recent decades, cancer cure and
      treatment continue to be a formidable challenge. Many sources, including plants,
      animals, and minerals, have been explored in the oncological field because of the
      possibility of identifying novel molecular therapeutics. Marine sponges are a
      prolific source of secondary metabolites, a number of which showed intriguing
      tumor chemopreventive and chemotherapeutic properties. Recently, Food and Drug
      Administration-approved drugs derived from marine sponges have been shown to
      reduce metastatic breast cancer, malignant lymphoma, and Hodgkin's disease. The
      chemopreventive and potential anticancer activity of marine sponge-derived
      compounds could be explained by multiple cellular and molecular mechanisms,
      including DNA protection, cell-cycle modulation, apoptosis, and anti-inflammatory
      activities as well as their ability to chemosensitize cancer cells to traditional
      antiblastic chemotherapy. The present article aims to depict the multiple
      mechanisms involved in the chemopreventive and therapeutic effects of marine
      sponges and critically explore the limitations and challenges associated with the
      development of marine sponge-based anticancer strategy.

PMID- 29027958
TI  - Adipose Tissue as a Strategic Source of Mesenchymal Stem Cells in Bone
      Regeneration: A Topical Review on the Most Promising Craniomaxillofacial
      Applications.
AB  - Bone regeneration in craniomaxillofacial surgery represents an issue that
      involves both surgical and aesthetic aspects. The most recent studies on bone
      tissue engineering involving adipose-derived stromal/stem cells (ASCs) have
      clearly demonstrated that such cells can play a crucial role in the treatment of
      craniomaxillofacial defects, given their strong commitment towards the osteogenic
      phenotype. A deeper knowledge of the molecular mechanisms underlying ASCs is
      crucial for a correct understanding of the potentialities of ASCs-based therapies
      in the most complex maxillofacial applications. In this topical review, we
      analyzed the molecular mechanisms of ASCs related to their support toward
      angiogenesis and osteogenesis, during bone regeneration. Moreover, we analyzed
      both case reports and clinical trials reporting the most promising clinical
      applications of ASCs in the treatment of craniomaxillofacial defects. Our study
      aimed to report the main molecular and clinical features shown by ASCs, used as a
      therapeutic support in bone engineering, as compared to the use of conventional
      autologous and allogeneic bone grafts.

PMID- 29027959
TI  - Radiation-Induced Changes of microRNA Expression Profiles in Radiosensitive and
      Radioresistant Leukemia Cell Lines with Different Levels of Chromosome
      Abnormalities.
AB  - In our study, we estimate an effect from chromosome aberrations and genome
      mutations on changes in microRNA expression profiles in cancer cell lines
      demonstrating different radiosensitivity. Here, cell viability and microRNA
      spectrum have been estimated 1, 4, and 24 h after irradiation. MiSeq high
      throughput sequencing system (Illumina, San Diego, CA, USA) is employed to
      perform microRNA spectrum estimation. In the K562 cell line, the number of
      expressed microRNAs in chromosomes demonstrates a more pronounced variation. An
      analysis of microRNA effects on signaling pathway activity demonstrates
      differences in post-transcriptional regulation of the expression of genes
      included into 40 signaling pathways. In the K562 cell line, microRNA dynamics
      analyzed for their dependence on chromosome localization show a wider scattering
      of microRNA expression values for a pair of chromosomes compared to the HL-60
      cell line. An analysis of microRNAs expression in the K562 and HL-60 cell lines
      after irradiation has shown that chromosome abnormalities can affect microRNA
      expression changes. A study of radiation-induced changes of microRNA expression
      profiles in the K562 and HL-60 cell lines has revealed a dependence of microRNA
      expression changes on the number of chromosome aberrations and genome mutations.

PMID- 29027960
TI  - A New Approach to Assess Lifetime Dietary Patterns Finds Lower Consumption of
      Animal Foods with Aging in a Longitudinal Analysis of a Health-Oriented Adventist
      Population.
AB  - Life-course diet patterns may impact risk of disease, but little is known about
      dietary trends with aging. In a retrospective longitudinal analysis we estimated
      lifetime intake of animal products and adherence to vegetarian dietary patterns
      among 51,082 Adventist Health Study-2 (AHS-2) subjects using data from a reliable
      life-course dietary (meats, dairy, eggs) questionnaire. Results showed a marked
      tendency to consume fewer animal products (in total) in older years and to reduce
      consumption of meat, poultry and fish, but not eggs or dairy. Among the 29% of
      elderly subjects who during their lifetime kept the same dietary pattern (LTS)
      were: LTS-vegans (1.1%), LTS-lacto-ovo vegetarians (31.2%), LTS-pesco vegetarians
      (0.49%), LTS-semi vegetarians (3.7%), and LTS-non-vegetarians (63.5%). Among the
      71% of switchers were "Converters" (59.7%) who moved towards and "Reverters"
      (9.1%) who moved away from vegetarian diets, and Multiverters (31.2%), who had
      moved in both directions. LTS-non-vegetarians, and also reverters, were more
      overweight and showed a less healthy lifestyle than others. We conclude that the
      dietary patterns are dynamic with strong trends to reduce animal foods and to
      adopt more vegetarian patterns with aging. The disease experience of subjects
      with different lifetime dietary patterns can be compared.

PMID- 29027962
TI  - Novel Therapeutics for Multiple Sclerosis Designed by Parasitic Worms.
AB  - The evolutionary response to endemic infections with parasitic worms (helminth)
      was the development of a distinct regulatory immune profile arising from the need
      to encapsulate the helminths while simultaneously repairing tissue damage.
      According to the old friend's hypothesis, the diminished exposure to these
      parasites in the developed world has resulted in a dysregulated immune response
      that contributes to the increased incidence of immune mediated diseases such as
      Multiple Sclerosis (MS). Indeed, the global distribution of MS shows an inverse
      correlation to the prevalence of helminth infection. On this basis, the
      possibility of treating MS with helminth infection has been explored in animal
      models and phase 1 and 2 human clinical trials. However, the possibility also
      exists that the individual immune modulatory molecules secreted by helminth
      parasites may offer a more defined therapeutic strategy.

PMID- 29027961
TI  - Dosis Facit Sanitatem-Concentration-Dependent Effects of Resveratrol on
      Mitochondria.
AB  - The naturally occurring polyphenol, resveratrol (RSV), is known for a broad range
      of actions. These include a positive impact on lifespan and health, but also pro
      apoptotic anti-cancer properties. Interestingly, cell culture experiments have
      revealed a strong impact of RSV on mitochondrial function. The compound was
      demonstrated to affect mitochondrial respiration, structure and mass of
      mitochondria as well as mitochondrial membrane potential and, ultimately,
      mitochondria-associated cell death pathways. Notably, the mitochondrial effects
      of RSV show a very strict and remarkable concentration dependency: At low
      concentrations, RSV (<50 MUM) fosters cellular antioxidant defense mechanisms,
      activates AMP-activated protein kinase (AMPK)- and sirtuin 1 (SIRT1)-linked
      pathways and enhances mitochondrial network formation. These mechanisms crucially
      contribute to the cytoprotective effects of RSV against toxins and disease
      related damage, in vitro and in vivo. However, at higher concentrations, RSV (>50
      MUM) triggers changes in (sub-)cellular Ca2+ homeostasis, disruption of
      mitochondrial membrane potential and activation of caspases selectively yielding
      apoptotic cancer cell death, in vitro and in vivo. In this review, we discuss the
      promising therapeutic potential of RSV, which is most probably related to the
      compound's concentration-dependent manipulation of mitochondrial function and
      structure.

PMID- 29027963
TI  - Optimizing the Nutritional Support of Adult Patients in the Setting of Cirrhosis.
AB  - AIM: The aim of this work is to develop a pragmatic approach in the assessment
      and management strategies of patients with cirrhosis in order to optimize the
      outcomes in this patient population. METHOD: A systematic review of literature
      was conducted through 8 July 2017 on the PubMed Database looking for key terms,
      such as malnutrition, nutrition, assessment, treatment, and cirrhosis. Articles
      and studies looking at associations between nutrition and cirrhosis were
      reviewed. RESULTS: An assessment of malnutrition should be conducted in two
      stages: the first, to identify patients at risk for malnutrition based on the
      severity of liver disease, and the second, to perform a complete
      multidisciplinary nutritional evaluation of these patients. Optimal management of
      malnutrition should focus on meeting recommended daily goals for caloric intake
      and inclusion of various nutrients in the diet. The nutritional goals should be
      pursued by encouraging and increasing oral intake or using other measures, such
      as oral supplementation, enteral nutrition, or parenteral nutrition. CONCLUSIONS:
      Although these strategies to improve nutritional support have been well
      established, current literature on the topic is limited in scope. Further
      research should be implemented to test if this enhanced approach is effective.

PMID- 29027964
TI  - Microglia and Monocytes/Macrophages Polarization Reveal Novel Therapeutic
      Mechanism against Stroke.
AB  - Stroke is a leading cause of morbidity and mortality worldwide, and consists of
      two types, ischemic and hemorrhagic. Currently, there is no effective treatment
      to increase the survival rate or improve the quality of life after ischemic and
      hemorrhagic stroke in the subacute to chronic phases. Therefore, it is necessary
      to establish therapeutic strategies to facilitate functional recovery in patients
      with stroke during both phases. Cell-based therapies, using microglia and
      monocytes/macrophages preconditioned by optimal stimuli and/or any therapies
      targeting these cells, might be an ideal therapeutic strategy for managing
      stroke. Microglia and monocytes/macrophages polarize to the classic pro
      inflammatory type (M1-like) or alternative protective type (M2-like) by optimal
      condition. Cell-based therapies using M2-like microglia and monocytes/macrophages
      might be protective therapeutic strategies against stroke for three reasons.
      First, M2-like microglia and monocytes/monocytes secrete protective remodeling
      factors, thus prompting neuronal network recovery via tissue (including neuronal)
      and vascular remodeling. Second, these cells could migrate to the injured
      hemisphere through the blood-brain barrier or choroid-plexus. Third, these cells
      could mitigate the extent of inflammation-induced injuries by suitable timing of
      therapeutic intervention. Although future translational studies are required, M2
      like microglia and monocytes/macrophages therapies are attractive for managing
      stroke based on their protective functions.

PMID- 29027967
TI  - Cusp Catastrophe Regression and Its Application in Public Health and Behavioral
      Research.
AB  - The cusp catastrophe model is an innovative approach for investigating a
      phenomenon that consists of both continuous and discrete changes in one modeling
      framework. However, its application to empirical health and behavior data has
      been hindered by the complexity in data-model fit. In this study, we reported our
      work in the development of a new modeling method-cusp catastrophe regression
      (RegCusp in short) by casting the cusp catastrophe into a statistical regression.
      With the RegCusp approach, unbiased model parameters can be estimated with the
      maximum likelihood estimation method. To validate the RegCusp method, a series of
      simulations were conducted to demonstrate the unbiasedness of parameter
      estimation. Since the estimated residual variance with the Fisher information
      matrix method was over-dispersed, a bootstrap re-sampling procedure was developed
      and used as a remedy. We also demonstrate the practical applicability of the
      RegCusp with empirical data from an NIH-funded project to evaluate an HIV
      prevention intervention program to educate adolescents in the Bahamas for condom
      use. Study findings indicated that the model parameters estimated with RegCusp
      were practically more meaningful than those estimated with comparable methods,
      especially the estimated cusp point.

PMID- 29027966
TI  - Myocardial Expression of Macrophage Migration Inhibitory Factor in Patients with
      Heart Failure.
AB  - Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory
      protein and contributes to several different inflammatory and ischemic/hypoxic
      diseases. MIF was shown to be cardioprotective in experimental myocardial
      ischemia/reperfusion injury and its expression is regulated by the transcription
      factor hypoxia-inducible factor (HIF)-1alpha. We here report on MIF expression in
      the failing human heart and assess myocardial MIF in different types of
      cardiomyopathy. Myocardial tissue samples from n = 30 patients were analyzed by
      quantitative Real-Time PCR. MIF and HIF-1alpha mRNA expression was analyzed in
      myocardial samples from patients with ischemic (ICM) and non-ischemic
      cardiomyopathy (NICM) and from patients after heart transplantation (HTX). MIF
      expression was elevated in myocardial samples from patients with ICM compared to
      NICM. Transplanted hearts showed lower MIF levels compared to hearts from
      patients with ICM. Expression of HIF-1alpha was analyzed and was shown to be
      significantly increased in ICM patients compared to patients with NICM. MIF and
      HIF-1alpha mRNA is expressed in the human heart. MIF and HIF-1alpha expression
      depends on the underlying type of cardiomyopathy. Patients with ICM show
      increased myocardial MIF and HIF-1alpha expression.

PMID- 29027968
TI  - Rapid Identification of Dipeptidyl Peptidase-IV (DPP-IV) Inhibitory Peptides from
      Ruditapes philippinarum Hydrolysate.
AB  - Dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides were rapidly identified from
      Ruditapes philippinarum hydrolysate. The hydrolysate was fractionated by ethanol
      precipitation and preparative reverse phase high-performance liquid
      chromatography (RP-HPLC). The fraction which showed the highest DPP-IV inhibitory
      activity was then analyzed by a high-throughput nano-liquid chromatography
      electrospray ionization tandem mass spectrometry (nano-LC ESI-MS/MS) method, and
      the sequences of peptides were identified based on the MS/MS spectra against the
      Mollusca protein data from the UniProt database. In total, 50 peptides were
      identified. Furthermore, molecular docking was used to identify potential DPP-IV
      inhibitors from the identified peptides. Docking results suggested that four
      peptides: FAGDDAPR, LAPSTM, FAGDDAPRA, and FLMESH, could bind pockets of DPP-IV
      through hydrogen bonds, pi-pi bonds, and charge interactions. The four peptides
      were chemically synthesized and tested for DPP-IV inhibitory activity. The
      results showed that they possessed DPP-IV inhibitory activity with IC50 values of
      168.72 MUM, 140.82 MUM, 393.30 MUM, and >500 MUM, respectively. These results
      indicate that R. philippinarum-derived peptides may have potential as functional
      food ingredients for the prevention of diabetes.

PMID- 29027965
TI  - Enhancing the Therapeutic Delivery of Oligonucleotides by Chemical Modification
      and Nanoparticle Encapsulation.
AB  - Oligonucleotide (ON) drugs, including small interfering RNA (siRNA), microRNA
      (miRNA) and antisense oligonucleotides, are promising therapeutic agents.
      However, their low membrane permeability and sensitivity to nucleases present
      challenges to in vivo delivery. Chemical modifications of the ON offer a
      potential solution to improve the stability and efficacy of ON drugs. Combined
      with nanoparticle encapsulation, delivery at the site of action and gene
      silencing activity of chemically modified ON drugs can be further enhanced. In
      the present review, several types of ON drugs, selection of chemical
      modification, and nanoparticle-based delivery systems to deliver these ON drugs
      are discussed.

PMID- 29027970
TI  - Stereopermutation on the Putative Structure of the Marine Natural Product
      Mucosin.
AB  - A stereodivergent total synthesis has been executed based on the plausibly
      misassigned structure of the unusual marine hydrindane mucosin (1). The
      topological connectivity of the four contiguous all-carbon stereocenters has been
      examined by selective permutation on the highlighted core. Thus, capitalizing on
      an unprecedented stereofacial preference of the cis-fused bicycle[4.3.0]non-3-ene
      system when a Michael acceptor motif is incorporated, copper-mediated conjugate
      addition furnished a single diastereomer. Cued by the relative relationship
      reported for the appendices in the natural product, the resulting anti-adduct was
      elaborated into a probative target structure 1*.

PMID- 29027969
TI  - New and Old Genes Associated with Primary and Established Responses to Cisplatin
      and Topotecan Treatment in Ovarian Cancer Cell Lines.
AB  - Low efficiency of chemotherapy in ovarian cancer results from the development of
      drug resistance. Cisplatin (CIS) and topotecan (TOP) are drugs used in
      chemotherapy of this cancer. We analyzed the development of CIS and TOP
      resistance in ovarian cancer cell lines. Incubation of drug sensitive cell lines
      (W1 and A2780) with cytostatic drugs was used to determine the primary response
      to CIS and TOP. Quantitative polymerase chain reaction (Q-PCR) was performed to
      measure the expression levels of the genes. We observed decreased expression of
      the MCTP1 gene in all resistant cell lines. We observed overexpression of the
      S100A3 and HERC5 genes in TOP-resistant cell lines. Increased expression of the
      S100A3 gene was also observed in CIS-resistant A2780 sublines. Overexpression of
      the C4orf18 gene was observed in CIS- and TOP-resistant A2780 sublines. A short
      time of exposure to CIS led to increased expression of the ABCC2 gene in the W1
      and A2780 cell lines and increased expression of the C4orf18 gene in the A2780
      cell line. A short time of exposure to TOP led to increased expression of the
      S100A3 and HERC5 genes in both sensitive cell lines, increased expression of the
      C4orf18 gene in the A2780 cell line and downregulation of the MCTP1 gene in the
      W1 cell line. Our results suggest that changes in expression of the MCTP1, S100A3
      and C4orf18 genes may be related to both CIS and TOP resistance. Increased
      expression of the HERC5 gene seems to be important only in TOP resistance.

PMID- 29027972
TI  - Special Issue "Synthesis and Applications of Oligonucleotide Conjugates".
AB  - The underlying idea of oligonucleotide conjugates is to provide oligonucleotide
      with some novel property [...].

PMID- 29027973
TI  - Smart Annotation of Cyclic Data Using Hierarchical Hidden Markov Models.
AB  - Cyclic signals are an intrinsic part of daily life, such as human motion and
      heart activity. The detailed analysis of them is important for clinical
      applications such as pathological gait analysis and for sports applications such
      as performance analysis. Labeled training data for algorithms that analyze these
      cyclic data come at a high annotation cost due to only limited annotations
      available under laboratory conditions or requiring manual segmentation of the
      data under less restricted conditions. This paper presents a smart annotation
      method that reduces this cost of labeling for sensor-based data, which is
      applicable to data collected outside of strict laboratory conditions. The method
      uses semi-supervised learning of sections of cyclic data with a known cycle
      number. A hierarchical hidden Markov model (hHMM) is used, achieving a mean
      absolute error of 0.041 +/- 0.020 s relative to a manually-annotated reference.
      The resulting model was also used to simultaneously segment and classify
      continuous, 'in the wild' data, demonstrating the applicability of using hHMM,
      trained on limited data sections, to label a complete dataset. This technique
      achieved comparable results to its fully-supervised equivalent. Our semi
      supervised method has the significant advantage of reduced annotation cost.
      Furthermore, it reduces the opportunity for human error in the labeling process
      normally required for training of segmentation algorithms. It also lowers the
      annotation cost of training a model capable of continuous monitoring of cycle
      characteristics such as those employed to analyze the progress of movement
      disorders or analysis of running technique.

PMID- 29027971
TI  - Chemotaxonomic Classification Applied to the Identification of Two Closely
      Related Citrus TCMs Using UPLC-Q-TOF-MS-Based Metabolomics.
AB  - This manuscript elaborates on the establishment of a chemotaxonomic
      classification strategy for closely-related Citrus fruits in Traditional Chinese
      Medicines (TCMs). UPLC-Q-TOF-MS-based metabolomics was applied to depict the
      variable chemotaxonomic markers and elucidate the metabolic mechanism of Citrus
      TCMs from different species and at different ripening stages. Metabolomics can
      capture a comprehensive analysis of small molecule metabolites and can provide a
      powerful approach to establish metabolic profiling, creating a bridge between
      genotype and phenotype. To further investigate the different metabolites in four
      closely-related Citrus TCMs, non-targeted metabolite profiling analysis was
      employed as an efficient technique to profile the primary and secondary
      metabolites. The results presented in this manuscript indicate that primary
      metabolites enable the discrimination of species, whereas secondary metabolites
      are associated with species and the ripening process. In addition, analysis of
      the biosynthetic pathway highlighted that the syntheses of flavone and flavone
      glycosides are deeply affected in Citrus ripening stages. Ultimately, this work
      might provide a feasible strategy for the authentication of Citrus fruits from
      different species and ripening stages and facilitate a better understanding of
      their different medicinal uses.

PMID- 29027974
TI  - Longitudinal Measurements of Tarnished Plant Bug (Hemiptera: Miridae)
      Susceptibility to Insecticides in Arkansas, Louisiana, and Mississippi:
      Associations with Insecticide Use and Insect Control Recommendations.
AB  - Concentration-response assays were conducted from 2008 through 2015 to measure
      the susceptibility of field populations of Lygus lineolaris (Palisot de Beauvois)
      from the Delta regions of Arkansas, Louisiana, and Mississippi to acephate,
      imidacloprid, thiamethoxam, permethrin, and sulfoxaflor. A total of 229 field
      populations were examined for susceptibility to acephate, 145 for susceptibility
      to imidacloprid, and 208 for susceptibility to thiamethoxam. Permethrin assays
      were conducted in 2014 and 2015 to measure levels of pyrethroid resistance in 44
      field populations, and sulfoxaflor assays were conducted against 24 field
      populations in 2015. Resistance to acephate and permethrin is as high or higher
      than that previously reported, although some populations, especially those
      exposed to permethrin, appear to be susceptible. Variable assay responses were
      measured for populations exposed to imidacloprid and thiamethoxam. Average
      response metrics suggest that populations are generally susceptible to the
      neonicotinoids, but a few populations from cotton fields experiencing control
      problems exhibited elevated LC50s. Efforts to associate variability in LC50s with
      recorded use of insecticides and estimated cotton insect losses and control costs
      suggest that intensive use of insecticides over several decades may have elevated
      general detoxifying enzymes in L. lineolaris and some field populations may be
      exhibiting resistance to multiple classes of insecticide. These results suggest
      that efforts should be made to manage these pests more efficiently with a reduced
      use of insecticides and alternative controls.

PMID- 29027975
TI  - Dietary Supplement Use during Preconception: The Australian Longitudinal Study on
      Women's Health.
AB  - Worldwide, dietary supplement use among reproductive aged women is becoming
      increasingly common. The aim of this study was to investigate dietary supplement
      use among Australian women during preconception. Self-reported data were
      collected prospectively for the Australian Longitudinal Study on Women's Health
      (ALSWH). The sample included 485 women aged 31-36 years, with supplement data,
      classified as preconception when completing Survey 5 of the ALSWH in 2009.
      Frequency and contingency tables were calculated and Pearson's chi-square test
      for associations between demographic variables and supplementation status was
      performed. Sixty-three per cent of women were taking at least one dietary
      supplement during preconception. Multiple-micronutrient supplements were the most
      commonly reported supplement (44%). Supplements containing folic acid and iodine
      were reported by 51% and 37% of preconception women, respectively. Folic acid
      (13%), omega-3 fatty acids (11%), vitamin C (7%), B vitamins (4%), iron (3%), and
      calcium (3%) were the most common single nutrients supplemented during
      preconception. Women trying to conceive, with no previous children, and born
      outside Australia were more likely to take dietary supplements. In Australia,
      dietary supplement use during preconception is relatively high. However,
      supplementation of recommended nutrients, including folic acid and iodine, could
      be improved.

PMID- 29027976
TI  - Development and Bioanalytical Applications of a White Light Reflectance
      Spectroscopy Label-Free Sensing Platform.
AB  - The development of a sensing platform based on white light reflectance
      spectroscopy (WLRS) is presented. The evolution of the system, from polymer film
      characterization and sensing of volatile organic compounds to biosensor for the
      label-free determination of either high (e.g., proteins) or low molecular weight
      analytes (e.g., pesticides), is described. At the same time, the passage from
      single to multi-analyte determinations, and from a laboratory prototype set-up to
      a compact device appropriate for on-site determination, is outlined. The
      improvements made on both the sensor and the optical set-up, and the concomitant
      advances in the analytical characteristics and the robustness of the assays
      performed with the different layouts, are also presented. Finally, the future
      perspectives of the system, aiming for the creation of a standalone instrument to
      be used by non-experts, will be discussed.

PMID- 29027978
TI  - Feedback System Control Optimized Electrospinning for Fabrication of an Excellent
      Superhydrophobic Surface.
AB  - Superhydrophobic surface, as a promising micro/nano material, has tremendous
      applications in biological and artificial investigations. The
      electrohydrodynamics (EHD) technique is a versatile and effective method for
      fabricating micro- to nanoscale fibers and particles from a variety of materials.
      A combination of critical parameters, such as mass fraction, ratio of N, N
      Dimethylformamide (DMF) to Tetrahydrofuran (THF), inner diameter of needle, feed
      rate, receiving distance, applied voltage as well as temperature, during
      electrospinning process, to determine the morphology of the electrospun
      membranes, which in turn determines the superhydrophobic property of the
      membrane. In this study, we applied a recently developed feedback system control
      (FSC) scheme for rapid identification of the optimal combination of these
      controllable parameters to fabricate superhydrophobic surface by one-step
      electrospinning method without any further modification. Within five rounds of
      experiments by testing totally forty-six data points, FSC scheme successfully
      identified an optimal parameter combination that generated electrospun membranes
      with a static water contact angle of 160 degrees or larger. Scanning electron
      microscope (SEM) imaging indicates that the FSC optimized surface attains unique
      morphology. The optimized setup introduced here therefore serves as a one-step,
      straightforward, and economic approach to fabricate superhydrophobic surface with
      electrospinning approach.

PMID- 29027977
TI  - Participation of the Halogens in Photochemical Reactions in Natural and Treated
      Waters.
AB  - Halide ions are ubiquitous in natural waters and wastewaters. Halogens play an
      important and complex role in environmental photochemical processes and in
      reactions taking place during photochemical water treatment. While inert to solar
      wavelengths, halides can be converted into radical and non-radical reactive
      halogen species (RHS) by sensitized photolysis and by reactions with secondary
      reactive oxygen species (ROS) produced through sunlight-initiated reactions in
      water and atmospheric aerosols, such as hydroxyl radical, ozone, and nitrate
      radical. In photochemical advanced oxidation processes for water treatment, RHS
      can be generated by UV photolysis and by reactions of halides with hydroxyl
      radicals, sulfate radicals, ozone, and other ROS. RHS are reactive toward organic
      compounds, and some reactions lead to incorporation of halogen into byproducts.
      Recent studies indicate that halides, or the RHS derived from them, affect the
      concentrations of photogenerated reactive oxygen species (ROS) and other reactive
      species; influence the photobleaching of dissolved natural organic matter (DOM);
      alter the rates and products of pollutant transformations; lead to covalent
      incorporation of halogen into small natural molecules, DOM, and pollutants; and
      give rise to certain halogen oxides of concern as water contaminants. The complex
      and colorful chemistry of halogen in waters will be summarized in detail and the
      implications of this chemistry for global biogeochemical cycling of halogen,
      contaminant fate in natural waters, and water purification technologies will be
      discussed.

PMID- 29027979
TI  - Molecular Mechanics of the Moisture Effect on Epoxy/Carbon Nanotube
      Nanocomposites.
AB  - The strong structural integrity of polymer nanocomposite is influenced in the
      moist environment; but the fundamental mechanism is unclear, including the basis
      for the interactions between the absorbed water molecules and the structure,
      which prevents us from predicting the durability of its applications across
      multiple scales. In this research, a molecular dynamics model of the epoxy/single
      walled carbon nanotube (SWCNT) nanocomposite is constructed to explore the
      mechanism of the moisture effect, and an analysis of the molecular interactions
      is provided by focusing on the hydrogen bond (H-bond) network inside the
      nanocomposite structure. The simulations show that at low moisture concentration,
      the water molecules affect the molecular interactions by favorably forming the
      water-nanocomposite H-bonds and the small cluster, while at high concentration
      the water molecules predominantly form the water-water H-bonds and the large
      cluster. The water molecules in the epoxy matrix and the epoxy-SWCNT interface
      disrupt the molecular interactions and deteriorate the mechanical properties.
      Through identifying the link between the water molecules and the nanocomposite
      structure and properties, it is shown that the free volume in the nanocomposite
      is crucial for its structural integrity, which facilitates the moisture
      accumulation and the distinct material deteriorations. This study provides
      insights into the moisture-affected structure and properties of the nanocomposite
      from the nanoscale perspective, which contributes to the understanding of the
      nanocomposite long-term performance under the moisture effect.

PMID- 29027982
TI  - Regional Sustainable Development Analysis Based on Information Entropy-Sichuan
      Province as an Example.
AB  - According to the implementation of a scientific development perspective,
      sustainable development needs to consider regional development, economic and
      social development, and the harmonious development of society and nature, but
      regional sustainable development is often difficult to quantify. Through an
      analysis of the structure and functions of a regional system, this paper
      establishes an evaluation index system, which includes an economic subsystem, an
      ecological environmental subsystem and a social subsystem, to study regional
      sustainable development capacity. A sustainable development capacity measure
      model for Sichuan Province was established by applying the information entropy
      calculation principle and the Brusselator principle. Each subsystem and entropy
      change in a calendar year in Sichuan Province were analyzed to evaluate Sichuan
      Province's sustainable development capacity. It was found that the established
      model could effectively show actual changes in sustainable development levels
      through the entropy change reaction system, at the same time this model could
      clearly demonstrate how those forty-six indicators from the three subsystems
      impact on the regional sustainable development, which could make up for the lack
      of sustainable development research.

PMID- 29027983
TI  - To Facilitate or Curb? The Role of Financial Development in China's Carbon
      Emissions Reduction Process: A Novel Approach.
AB  - With the Paris Agreement coming into effect, China, as the largest CO2 emitter in
      the world, will be facing greater pressure to reduce its carbon emissions. This
      paper discusses how to solve this issue from the perspective of financial
      development in China. Although many studies have analyzed its impact on carbon
      emissions, the conclusions are contradictory. A major criticism of the existing
      studies is the reasonability of the selection of appropriate indicators and panel
      estimation techniques. Almost all studies use only one or limited indicators to
      represent the financial development and ignore the cross-sectional dependence. To
      fulfil the gaps mentioned above, a financial development index system is built,
      and with the framework of the STIRPAT (Stochastic impacts by regression on
      population, affluence, and technology) model, this paper applies an ARDL approach
      to investigating the long-run relationship between financial development and
      carbon emissions and a dynamic panel error-corrected model to capture the short
      run impact. The empirical results show that financial development can improve
      carbon emissions, and such impact not only shows a regional difference but also
      reflects the features of stage differences. Additionally, based on the discussion
      on seven specific aspects of financial development, our findings can be helpful
      for policy makers to enact corresponding policies to realize the goal of reducing
      carbon emissions in China.

PMID- 29027980
TI  - The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level
      Analysis of the miRNome.
AB  - Ubiquitous exposure to bisphenol A (BPA), an endocrine disruptor (ED), has raised
      concerns for both human and ecosystem health. Epigenetic factors, including
      microRNAs (miRNAs), are key regulators of gene expression during cancer. The
      effect of BPA exposure on the zebrafish epigenome remains poorly characterized.
      Zebrafish represents an excellent model to study cancer as the organism develops
      a disease that resembles human cancer. Using zebrafish as a systems toxicology
      model, we hypothesized that chronic BPA-exposure impacts the miRNome in adult
      zebrafish and establishes an epigenome more susceptible to cancer development.
      After a 3 week exposure to 100 nM BPA, RNA from the liver was extracted to
      perform high throughput mRNA and miRNA sequencing. Differential expression (DE)
      analyses comparing BPA-exposed to control specimens were performed using
      established bioinformatics pipelines. In the BPA-exposed liver, 6188 mRNAs and 15
      miRNAs were differently expressed (q <= 0.1). By analyzing human orthologs of the
      DE zebrafish genes, signatures associated with non-alcoholic fatty liver disease
      (NAFLD), oxidative phosphorylation, mitochondrial dysfunction and cell cycle were
      uncovered. Chronic exposure to BPA has a significant impact on the liver miRNome
      and transcriptome in adult zebrafish with the potential to cause adverse health
      outcomes including cancer.

PMID- 29027981
TI  - BACE1 Function and Inhibition: Implications of Intervention in the Amyloid
      Pathway of Alzheimer's Disease Pathology.
AB  - Alzheimer's disease (AD) is a fatal progressive neurodegenerative disorder
      characterized by increasing loss in memory, cognition, and function of daily
      living. Among the many pathologic events observed in the progression of AD,
      changes in amyloid beta peptide (Abeta) metabolism proceed fastest, and precede
      clinical symptoms. BACE1 (beta-secretase 1) catalyzes the initial cleavage of the
      amyloid precursor protein to generate Abeta. Therefore inhibition of BACE1
      activity could block one of the earliest pathologic events in AD. However,
      therapeutic BACE1 inhibition to block Abeta production may need to be balanced
      with possible effects that might result from diminished physiologic functions
      BACE1, in particular processing of substrates involved in neuronal function of
      the brain and periphery. Potentials for beneficial or consequential effects
      resulting from pharmacologic inhibition of BACE1 are reviewed in context of
      ongoing clinical trials testing the effect of BACE1 candidate inhibitor drugs in
      AD populations.

PMID- 29027985
TI  - Triterpenoids from Ocimum labiatum Activates Latent HIV-1 Expression In Vitro:
      Potential for Use in Adjuvant Therapy.
AB  - Latent HIV reservoirs in infected individuals prevent current treatment from
      eradicating infection. Treatment strategies against latency involve adjuvants for
      viral reactivation which exposes viral particles to antiretroviral drugs. In this
      study, the effect of novel triterpenoids isolated from Ocimum labiatum on HIV-1
      expression was measured through HIV-1 p24 antigen capture in the U1 latency model
      of HIV-1 infection and in peripheral blood mononuclear cells (PBMCs) of infected
      patients on combination antiretroviral therapy (cART). The mechanism of viral
      reactivation was determined through the compound's effect on cytokine production,
      histone deacetylase (HDAC) inhibition, and protein kinase C (PKC) activation.
      Cytotoxicity of the triterpenoids was determined using a tetrazolium dye and flow
      cytometry. The isolated triterpene isomers, 3-hydroxy-4,6a,6b,11,12,14b
      hexamethyl-1,2,3,4,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-octadecahydropicene
      4,8a-dicarboxylic acid (HHODC), significantly (p < 0.05) induced HIV-1 expression
      in a dose-dependent manner in U1 cells at non-cytotoxic concentrations. HHODC
      also induced viral expression in PBMCs of HIV-1 infected patients on cART. In
      addition, the compound up-regulated the production of interleukin (IL)-2, IL-6,
      tumour necrosis factor (TNF)-alpha, and interferon (IFN)-gamma but had no effect
      on HDAC and PKC activity, suggesting cytokine upregulation as being involved in
      latency activation. The observed in vitro reactivation of HIV-1 introduces the
      adjuvant potential of HHODC for the first time here.

PMID- 29027984
TI  - The Effect of Intra-articular Injection of Autologous Microfragmented Fat Tissue
      on Proteoglycan Synthesis in Patients with Knee Osteoarthritis.
AB  - Osteoarthritis (OA) is one of the leading musculoskeletal disorders in the adult
      population. It is associated with cartilage damage triggered by the deterioration
      of the extracellular matrix tissue. The present study explores the effect of
      intra-articular injection of autologous microfragmented adipose tissue to host
      chondrocytes and cartilage proteoglycans in patients with knee OA. A prospective,
      non-randomized, interventional, single-center, open-label clinical trial was
      conducted from January 2016 to April 2017. A total of 17 patients were enrolled
      in the study, and 32 knees with osteoarthritis were assessed. Surgical
      intervention (lipoaspiration) followed by tissue processing and intra-articular
      injection of the final microfragmented adipose tissue product into the affected
      knee(s) was performed in all patients. Patients were assessed for visual analogue
      scale (VAS), delayed gadolinium-enhanced magnetic resonance imaging of cartilage
      (dGEMRIC) and immunoglobulin G (IgG) glycans at the baseline, three, six and 12
      months after the treatment. Magnetic resonance sequence in dGEMRIC due to
      infiltration of the anionic, negatively charged contrast gadopentetate
      dimeglumine (Gd-DTPA2-) into the cartilage indicated that the contents of
      cartilage glycosaminoglycans significantly increased in specific areas of the
      treated knee joint. In addition, dGEMRIC consequently reflected subsequent
      changes in the mechanical axis of the lower extremities. The results of our study
      indicate that the use of autologous and microfragmented adipose tissue in
      patients with knee OA (measured by dGEMRIC MRI) increased glycosaminoglycan (GAG)
      content in hyaline cartilage, which is in line with observed VAS and clinical
      results.

PMID- 29027986
TI  - Effects of Conjugated Linoleic Acid Supplementation on the Expression Profile of
      miRNAs in Porcine Adipose Tissue.
AB  - Conjugated linoleic acids (CLAs) play a major role in adipocyte differentiation
      and lipid metabolism in animals. MicroRNAs (miRNAs) appear to be involved in many
      biological processes in adipose tissue. However, the specific influence on miRNAs
      by CLA supplementation in porcine adipose tissue remains unclear. Thus, we
      continuously added 1.5% CLA to the pig diet from the embryo stage to the
      finishing period and conducted a high-throughput sequencing approach to analyse
      the changes in adipose tissue miRNAs. We identified 283 known porcine miRNAs, and
      14 miRNAs were differentially expressed in response to CLA treatment. A Kyoto
      Encyclopedia of Genes and Genomes (KEGG) analysis showed that the targets of the
      14 differentially expressed miRNAs were involved in the Wnt signalling pathway.
      The CLA treatment downregulated the gene expression of PPARgamma, C/EBPalpha,
      FAS, and FATP1 in both subcutaneous and abdominal fat tissues; the analysis
      showed that ssc-miR-21 expression was significantly correlated with PPARgamma
      expression (p<0.05), and speculated that ssc-miR-21 might influence adipogenesis
      through PPARgamma. In conclusion, our study analysed the miRNA profiles in
      porcine adipose tissues by CLA treatment, and demonstrated that miRNAs are
      important regulators of fat lipogenesis. This study provides valuable information
      for the molecular regulatory mechanism of CLA on adipose tissue.

PMID- 29027987
TI  - Chromosomal Evolution in Chiroptera.
AB  - Chiroptera is the second largest order among mammals, with over 1300 species in
      21 extant families. The group is extremely diverse in several aspects of its
      natural history, including dietary strategies, ecology, behavior and morphology.
      Bat genomes show ample chromosome diversity (from 2n = 14 to 62). As with other
      mammalian orders, Chiroptera is characterized by clades with low, moderate and
      extreme chromosomal change. In this article, we will discuss trends of karyotypic
      evolution within distinct bat lineages (especially Phyllostomidae, Hipposideridae
      and Rhinolophidae), focusing on two perspectives: evolution of genome
      architecture, modes of chromosomal evolution, and the use of chromosome data to
      resolve taxonomic problems.

PMID- 29027988
TI  - The History of Tree and Shrub Taxa on Bol'shoy Lyakhovsky Island (New Siberian
      Archipelago) since the Last Interglacial Uncovered by Sedimentary Ancient DNA and
      Pollen Data.
AB  - Ecosystem boundaries, such as the Arctic-Boreal treeline, are strongly coupled
      with climate and were spatially highly dynamic during past glacial-interglacial
      cycles. Only a few studies cover vegetation changes since the last interglacial,
      as most of the former landscapes are inundated and difficult to access. Using
      pollen analysis and sedimentary ancient DNA (sedaDNA) metabarcoding, we reveal
      vegetation changes on Bol'shoy Lyakhovsky Island since the last interglacial from
      permafrost sediments. Last interglacial samples depict high levels of floral
      diversity with the presence of trees (Larix, Picea, Populus) and shrubs (Alnus,
      Betula, Ribes, Cornus, Saliceae) on the currently treeless island. After the Last
      Glacial Maximum, Larix re-colonised the island but disappeared along with most
      shrub taxa. This was probably caused by Holocene sea-level rise, which led to
      increased oceanic conditions on the island. Additionally, we applied two newly
      developed larch-specific chloroplast markers to evaluate their potential for
      tracking past population dynamics from environmental samples. The novel markers
      were successfully re-sequenced and exhibited two variants of each marker in last
      interglacial samples. SedaDNA can track vegetation changes as well as genetic
      changes across geographic space through time and can improve our understanding of
      past processes that shape modern patterns.

PMID- 29027989
TI  - Inhibition of neddylation by MLN4924 improves neointimal hyperplasia and promotes
      apoptosis of vascular smooth muscle cells through p53 and p62.
AB  - Targeting apoptosis of vascular smooth muscle cells (VSMCs) represents an
      attractive approach to diminish the occurrence of restenosis. Neddylation is a
      highly conserved post-translational modification process and inhibition of
      neddylation has been shown to regulate apoptosis of other cells. However, the
      impacts of neddylation inhibition on VSMCs and neointimal hyperplasia have not
      been studied. In our present study, we have shown that MLN4924, a selective
      inhibitor of NEDD8-activating enzyme (NAE), markedly inhibited neointimal
      hyperplasia and accumulation of VSMCs, whereas increased apoptosis in the
      vascular wall. In vitro studies revealed that MLN4924 induced G2/M arrest and
      apoptosis of human VSMCs. Knockdown of NAE1 had similar effects. MLN4924
      upregulated p53 and p62 in human VSMCs. Knockdown of either p53 or p62 mitigated
      the impacts of MLN4924 on G2/M arrest and apoptosis. Moreover, p53 knockdown
      abolished MLN4924-induced upregulation of p62. Finally, smooth muscle p53
      knockout mice were generated and subjected to femoral artery injury and MLN4924
      treatment. Deficiency of p53 in smooth muscle blocked the effects of MLN4924 on
      neointimal hyperplasia and apoptosis. Together, our results revealed that
      neddylation inhibition induces apoptosis through p53 and p62 in VSMCs and
      improves neointimal hyperplasia mainly by promoting apoptosis through smooth
      muscle p53 in mice. These pre-clinical data provide strong translational
      implications for targeting restenosis by perturbation of neddylation using
      MLN4924.

PMID- 29027990
TI  - IL6 blockade potentiates the anti-tumor effects of gamma-secretase inhibitors in
      Notch3-expressing breast cancer.
AB  - Notch pathways have important roles in carcinogenesis including pathways
      involving the Notch1 and Notch2 oncogenes. Pan-Notch inhibitors, such as gamma
      secretase inhibitors (GSIs), have been used in the clinical trials, but the
      outcomes of these trials have been insufficient and have yielded unclear. In the
      present study, we demonstrated that GSIs, such as MK-0752 and RO4929097, inhibit
      breast tumor growth, but increase the breast cancer stem cell (BCSC) population
      in Notch3-expressing breast cancer cells, in a process that is coupled with IL6
      induction and is blocked by the IL6R antagonist Tocilizumab (TCZ). IL6 induction
      results from inhibition of Notch3-Hey2 signaling through MK-0752. Furthermore,
      HIF1alpha upregulates Notch3 expression via direct binding to the Notch3 promoter
      and subsequently downregulates BCSCs by decreasing the IL6 levels in Notch3
      expressing breast cancer cells. Utilizing both breast cancer cell line xenografts
      and patient-derived xenografts (PDX), we showed that the combination of MK-0752
      and Tocilizumab significantly decreases BCSCs and inhibits tumor growth and thus
      might serve as a novel therapeutic strategy for treating women with Notch3
      expressing breast cancers.

PMID- 29027992
TI  - Deficiency of Parkinson's disease-related gene Fbxo7 is associated with impaired
      mitochondrial metabolism by PARP activation.
AB  - This corrects the article DOI: 10.1038/cdd.2016.104.

PMID- 29027991
TI  - N6-isopentenyladenosine dual targeting of AMPK and Rab7 prenylation inhibits
      melanoma growth through the impairment of autophagic flux.
AB  - Targeting the autophagic process is considered a promising therapeutic strategy
      in cancer since a great number of tumors, including melanoma, show high basal
      levels of protective autophagy that contributes to tumor progression and
      chemoresistance. Here, exploiting both in vitro and in vivo approaches, we
      identified N6-isopentenyladenosine (iPA), an end product of the mevalonate
      pathway, as a novel autophagy inhibitor with an interesting anti-melanoma
      activity. iPA, after being phosphorylated by adenosine kinase into 5'-iPA
      monophosphate, induces autophagosome accumulation through AMPK activation,
      measured by increased fluorescent GFP-LC3 puncta and enhanced conversion into the
      lipidated autophagosome-associated LC3-II. However, at a later stage iPA blocks
      the autophagic flux monitored by p62 accumulation, Luciferase reporter-based
      assay for LC3 turnover in living cells and fluorescence of a tandem RFP-GFP-LC3
      construct. Impaired autophagic flux is due to the block of autophagosome-lysosome
      fusion through the defective localization and function of Rab7, whose prenylation
      is inhibited by iPA, resulting in a net inhibition of autophagy completion that
      finally leads to melanoma apoptotic cell death. AMPK silencing prevents apoptosis
      upon iPA treatment, whereas basal autophagosome turnover is still inhibited due
      to unprenylated Rab7. These results strongly support the advantage of targeting
      autophagy for therapeutic gain in melanoma and provide the preclinical rational
      to further investigate the antitumor action of iPA, able to coordinately induce
      autophagosome accumulation and inhibit the autophagic flux, independently
      targeting AMPK and Rab7 prenylation. This property may be particularly useful for
      the selective killing of tumors, like melanoma, that frequently develop
      chemotherapy resistance due to protective autophagy activation.

PMID- 29027993
TI  - Current pharmacotherapy for obesity.
AB  - More than one-third of adults in the USA have obesity, which causes, exacerbates
      or adversely impacts numerous medical comorbidities, including diabetes mellitus
      and cardiovascular disease. Despite intensive lifestyle modifications, the
      disease severity warrants further aggressive intervention, including
      pharmacotherapy, medical devices and bariatric surgery. Noninvasive anti-obesity
      drugs have thus now resurfaced as targeted adjunctive therapeutic approaches to
      intensive lifestyle intervention, bridging the gap between lifestyle and
      bariatric surgery. In this Review, we discuss FDA-approved anti-obesity drugs in
      terms of safety and efficacy. As most of these drugs have a mean percentage
      weight loss reported in clinical trials but individual variations in response
      rates, a future direction of obesity pharmacotherapy research might include the
      potential for personalized medicine to target early responders to these anti
      obesity drugs.

PMID- 29027994
TI  - Bone diseases: Romosozumab - on track or derailed?

PMID- 29027995
TI  - Microbiota: FMT transiently improves insulin sensitivity.

PMID- 29027997
TI  - Microdiversification in genome-streamlined ubiquitous freshwater Actinobacteria.
AB  - Actinobacteria of the acI lineage are the most abundant microbes in freshwater
      systems, but there are so far no pure living cultures of these organisms,
      possibly because of metabolic dependencies on other microbes. This, in turn, has
      hampered an in-depth assessment of the genomic basis for their success in the
      environment. Here we present genomes from 16 axenic cultures of acI
      Actinobacteria. The isolates were not only of minute cell size, but also among
      the most streamlined free-living microbes, with extremely small genome sizes (1.2
      1.4 Mbp) and low genomic GC content. Genome reduction in these bacteria might
      have led to auxotrophy for various vitamins, amino acids and reduced sulphur
      sources, thus creating dependencies to co-occurring organisms (the 'Black Queen'
      hypothesis). Genome analyses, moreover, revealed a surprising degree of inter-
      and intraspecific diversity in metabolic pathways, especially of carbohydrate
      transport and metabolism, and mainly encoded in genomic islands. The striking
      genotype microdiversification of acI Actinobacteria might explain their global
      success in highly dynamic freshwater environments with complex seasonal patterns
      of allochthonous and autochthonous carbon sources. We propose a new order within
      Actinobacteria ('Candidatus Nanopelagicales') with two new genera ('Candidatus
      Nanopelagicus' and 'Candidatus Planktophila') and nine new species.

PMID- 29027996
TI  - Aquatic urban ecology at the scale of a capital: community structure and
      interactions in street gutters.
AB  - In most cities, streets are designed for collecting and transporting dirt,
      litter, debris, storm water and other wastes as a municipal sanitation system.
      Microbial mats can develop on street surfaces and form microbial communities that
      have never been described. Here, we performed the first molecular inventory of
      the street gutter-associated eukaryotes across the entire French capital of Paris
      and the non-potable waters sources. We found that the 5782 OTUs (operational
      taxonomic units) present in the street gutters which are dominated by diatoms
      (photoautotrophs), fungi (heterotrophs), Alveolata and Rhizaria, includes
      parasites, consumers of phototrophs and epibionts that may regulate the dynamics
      of gutter mat microbial communities. Network analyses demonstrated that street
      microbiome present many species restricted to gutters, and an overlapping
      composition between the water sources used for street cleaning (for example,
      intra-urban aquatic networks and the associated rivers) and the gutters. We
      propose that street gutters, which can cover a significant surface area of cities
      worldwide, potentially have important ecological roles in the remediation of
      pollutants or downstream wastewater treatments, might also be a niche for growth
      and dissemination of putative parasite and pathogens.

PMID- 29027998
TI  - Temporal dynamics of uncultured viruses: a new dimension in viral diversity.
AB  - Recent work has vastly expanded the known viral genomic sequence space, but the
      seasonal dynamics of viral populations at the genome level remain unexplored.
      Here we followed the viral community in a freshwater lake for 1 year using genome
      resolved viral metagenomics, combined with detailed analyses of the viral
      community structure, associated bacterial populations and environmental
      variables. We reconstructed 8950 complete and partial viral genomes, the majority
      of which were not persistent in the lake throughout the year, but instead
      continuously succeeded each other. Temporal analysis of 732 viral genus-level
      clusters demonstrated that one-fifth were undetectable at specific periods of the
      year. Based on host predictions for a subset of reconstructed viral genomes, we
      for the first time reveal three distinct patterns of host-pathogen dynamics,
      where the viruses may peak before, during or after the peak in their host's
      abundance, providing new possibilities for modelling of their interactions. Time
      series metagenomics opens up a new dimension in viral profiling, which is
      essential to understand the full scale of viral diversity and evolution, and the
      ecological roles of these important factors in the global ecosystem.

PMID- 29027999
TI  - A population genomics approach shows widespread geographical distribution of
      cryptic genomic forms of the symbiotic fungus Rhizophagus irregularis.
AB  - Arbuscular mycorrhizal fungi (AMF; phylum Gomeromycota) associate with plants
      forming one of the most successful microbe-plant associations. The fungi promote
      plant diversity and have a potentially important role in global agriculture.
      Plant growth depends on both inter- and intra-specific variation in AMF. It was
      recently reported that an unusually large number of AMF taxa have an
      intercontinental distribution, suggesting long-distance gene flow for many AMF
      species, facilitated by either long-distance natural dispersal mechanisms or
      human-assisted dispersal. However, the intercontinental distribution of AMF
      species has been questioned because the use of very low-resolution markers may be
      unsuitable to detect genetic differences among geographically separated AMF, as
      seen with some other fungi. This has been untestable because of the lack of
      population genomic data, with high resolution, for any AMF taxa. Here we use
      phylogenetics and population genomics to test for intra-specific variation in
      Rhizophagus irregularis, an AMF species for which genome sequence information
      already exists. We used ddRAD sequencing to obtain thousands of markers
      distributed across the genomes of 81 R. irregularis isolates and related species.
      Based on 6 888 variable positions, we observed significant genetic divergence
      into four main genetic groups within R. irregularis, highlighting that previous
      studies have not captured underlying genetic variation. Despite considerable
      genetic divergence, surprisingly, the variation could not be explained by
      geographical origin, thus also supporting the hypothesis for at least one AMF
      species of widely dispersed AMF genotypes at an intercontinental scale. Such
      information is crucial for understanding AMF ecology, and how these fungi can be
      used in an environmentally safe way in distant locations.

PMID- 29028000
TI  - Influence of resistance breeding in common bean on rhizosphere microbiome
      composition and function.
AB  - The rhizosphere microbiome has a key role in plant growth and health, providing a
      first line of defense against root infections by soil-borne pathogens. Here, we
      investigated the composition and metabolic potential of the rhizobacterial
      community of different common bean (Phaseolus vulgaris) cultivars with variable
      levels of resistance to the fungal root pathogen Fusarium oxysporum (Fox). For
      the different bean cultivars grown in two soils with contrasting physicochemical
      properties and microbial diversity, rhizobacterial abundance was positively
      correlated with Fox resistance. Pseudomonadaceae, bacillaceae, solibacteraceae
      and cytophagaceae were more abundant in the rhizosphere of the Fox-resistant
      cultivar. Network analyses showed a modular topology of the rhizosphere
      microbiome of the Fox-resistant cultivar, suggesting a more complex and highly
      connected bacterial community than in the rhizosphere of the Fox-susceptible
      cultivar. Metagenome analyses further revealed that specific functional traits
      such as protein secretion systems and biosynthesis genes of antifungal phenazines
      and rhamnolipids were more abundant in the rhizobacterial community of the Fox
      resistant cultivar. Our findings suggest that breeding for Fox resistance in
      common bean may have co-selected for other unknown plant traits that support a
      higher abundance of specific beneficial bacterial families in the rhizosphere
      with functional traits that reinforce the first line of defense.

PMID- 29028001
TI  - Soil protist communities form a dynamic hub in the soil microbiome.
AB  - Soil microbes are essential for soil fertility. However, most studies focus on
      bacterial and/or fungal communities, while the top-down drivers of this
      microbiome composition, protists, remain poorly understood. Here, we investigated
      how soil amendments affect protist communities and inferred potential
      interactions with bacteria and fungi. Specific fertilization treatments impacted
      both the structure and function of protist communities. Organic fertilizer
      amendment strongly reduced the relative abundance of plant pathogenic protists
      and increased bacterivorous and omnivorous protists. The addition of individual
      biocontrol bacteria and fungi further altered the soil protist community
      composition, and eventually function. Network analysis integrating protist,
      bacterial and fungal community data, placed protists as a central hub in the soil
      microbiome, linking diverse bacterial and fungal populations. Given their dynamic
      response to soil management practices and key position in linking soil microbial
      networks, protists may provide the leverage between soil management and the
      enhancement of bacterial and fungal microbiota at the service of improved soil
      health.

PMID- 29028003
TI  - Bacterial secretion of D-arginine controls environmental microbial biodiversity.
AB  - Bacteria face tough competition in polymicrobial communities. To persist in a
      specific niche, many species produce toxic extracellular effectors to interfere
      with the growth of nearby microbes. These effectors include the recently reported
      non-canonical D-amino acids (NCDAAs). In Vibrio cholerae, the causative agent of
      cholera, NCDAAs control cell wall integrity in stationary phase. Here, an
      analysis of the composition of the extracellular medium of V. cholerae revealed
      the unprecedented presence of D-Arg. Compared with other D-amino acids, D-Arg
      displayed higher potency and broader toxicity in terms of the number of bacterial
      species affected. Tolerance to D-Arg was associated with mutations in the
      phosphate transport and chaperone systems, whereas D-Met lethality was suppressed
      by mutations in cell wall determinants. These observations suggest that NCDAAs
      target different cellular processes. Finally, even though virtually all Vibrio
      species are tolerant to D-Arg, only a few can produce this D-amino acid. Indeed,
      we demonstrate that D-Arg may function as part of a cooperative strategy in
      vibrio communities to protect non-producing members from competing bacteria.
      Because NCDAA production is widespread in bacteria, we anticipate that D-Arg is a
      relevant modulator of microbial subpopulations in diverse ecosystems.

PMID- 29028004
TI  - Geobiological feedbacks and the evolution of thermoacidophiles.
AB  - Oxygen-dependent microbial oxidation of sulfur compounds leads to the
      acidification of natural waters. How acidophiles and their acidic habitats
      evolved, however, is largely unknown. Using 16S rRNA gene abundance and
      composition data from 72 hot springs in Yellowstone National Park, Wyoming, we
      show that hyperacidic (pH<3.0) hydrothermal ecosystems are dominated by a limited
      number of archaeal lineages with an inferred ability to respire O2. Phylogenomic
      analyses of 584 existing archaeal genomes revealed that hyperacidophiles evolved
      independently multiple times within the Archaea, each coincident with the
      emergence of the ability to respire O2, and that these events likely occurred in
      the recent evolutionary past. Comparative genomic analyses indicated that
      archaeal thermoacidophiles from independent lineages are enriched in similar
      protein-coding genes, consistent with convergent evolution aided by horizontal
      gene transfer. Because the generation of acidic environments and their successful
      habitation characteristically require O2, these results suggest that
      thermoacidophilic Archaea and the acidity of their habitats co-evolved after the
      evolution of oxygenic photosynthesis. Moreover, it is likely that dissolved O2
      concentrations in thermal waters likely did not reach levels capable of
      sustaining aerobic thermoacidophiles and their acidifying activity until ~0.8 Ga,
      when present day atmospheric levels were reached, a time period that is supported
      by our estimation of divergence times for archaeal thermoacidophilic clades.

PMID- 29028007
TI  - Endoscopic optical coherence tomography with a focus-adjustable probe.
AB  - We present a focus-adjustable endoscopic probe for optical coherence tomography
      (OCT), which is able to acquire images with different focal planes and overcome
      depth-of-focus limitations by image fusing. The use of a two-way shape-memory
      alloy spring enables the probe to adjust working distance over 1.5 mm, providing
      a large scanning range with high resolution and no sensitivity loss. Equipped
      with a homemade hollow-core ultrasonic motor, the probe is capable of performing
      an unobstructed 360 deg field-of-view distal scanning. Both the axial resolution
      and the best lateral resolution are ~4  MUm, with a sensitivity of 100.3 dB.
      Spectral-domain OCT imaging of phantom and biological tissues with the probe is
      also demonstrated.

PMID- 29028008
TI  - Atmospheric boundary layer CO2 remote sensing with a direct detection LIDAR
      instrument based on a widely tunable optical parametric source.
AB  - We report on the capability of a direct detection differential absorption lidar
      (DIAL) for range resolved and integrated path (IPDIAL) remote sensing of CO2 in
      the atmospheric boundary layer (ABL). The laser source is an amplified nested
      cavity optical parametric oscillator (NesCOPO) emitting approximately 8 mJ at the
      two measurement wavelengths selected near 2050 nm. Direct detection atmospheric
      measurements are taken from the ground using a 30 Hz frequency switching between
      emitted wavelengths. Results show that comparable precision measurements are
      achieved in DIAL and IPDIAL modes (not better than a few ppm) on high SNR targets
      such as near range ABL aerosol and clouds, respectively. Instrumental limitations
      are analyzed and degradation due to cloud scattering variability is discussed to
      explain observed DIAL and IPDIAL limitations.

PMID- 29028002
TI  - Cyanophage-encoded lipid desaturases: oceanic distribution, diversity and
      function.
AB  - Cyanobacteria are among the most abundant photosynthetic organisms in the oceans;
      viruses infecting cyanobacteria (cyanophages) can alter cyanobacterial
      populations, and therefore affect the local food web and global biochemical
      cycles. These phages carry auxiliary metabolic genes (AMGs), which rewire various
      metabolic pathways in the infected host cell, resulting in increased phage
      fitness. Coping with stress resulting from photodamage appears to be a central
      necessity of cyanophages, yet the overall mechanism is poorly understood. Here we
      report a novel, widespread cyanophage AMG, encoding a fatty acid desaturase
      (FAD), found in two genotypes with distinct geographical distribution. FADs are
      capable of modulating the fluidity of the host's membrane, a fundamental stress
      response in living cells. We show that both viral FAD (vFAD) families are Delta9
      lipid desaturases, catalyzing the desaturation at carbon 9 in C16 fatty acid
      chains. In addition, we present a comprehensive fatty acid profiling for marine
      cyanobacteria, which suggests a unique desaturation pathway of medium- to long
      chain fatty acids no longer than C16, in accordance with the vFAD activity. Our
      findings suggest that cyanophages are capable of fiddling with the infected
      host's membranes, possibly leading to increased photoprotection and potentially
      enhancing viral-encoded photosynthetic proteins, resulting in a new viral
      metabolic network.

PMID- 29028006
TI  - Polymorphism of antibiotic-inactivating enzyme driven by ecology expands the
      environmental resistome.
AB  - The environmental resistome has been recognized as the origin and reservoir of
      antibiotic resistance genes and considered to be dynamic and ever expanding. In
      this study, a targeted gene sequencing approach revealed that the polymorphic
      diversity of the aminoglycoside-inactivating enzyme AAC(6')-Ib was ecological
      niche-specific. AAC(6')-Ib-cr, previously known as a clinical variant, was
      prevalent in various soils and the intestines of chickens and humans, suggesting
      that this variant might not have arisen from adaptive mutations in the clinic but
      instead originated from the environment. Furthermore, ecologically dominant
      polymorphic variants of AAC(6')-Ib were characterized and found to display
      different substrate specificities for quinolones and aminoglycosides, conferring
      the altered resistance spectra. Interestingly, a novel variant with the D179Y
      substitution showed an extended resistance spectrum to the recently developed
      fluoroquinolone gemifloxacin. Our results suggest that soil and animal
      microbiomes could be major reservoirs of antibiotic resistance; polymorphic
      diversity expands the antibiotic resistome in the environment, resulting in the
      potential emergence of novel resistance.

PMID- 29028009
TI  - Extended polar decomposition method of Mueller matrices for turbid media in
      reflection geometry.
AB  - The polar decomposition method for Mueller matrices proposed by Lu-Chipman has
      been demonstrated and validated for many applications. However, in some
      situations, e.g., when analyzing the Mueller matrix of birefringent turbid media
      with Mie-sized scatterers acquired in reflection geometry, the method may suffer
      from limitations due to the assumptions required by this method. Here we extend
      the Lu-Chipman method and show that it can provide more reasonable results for
      these situations. The method has been validated experimentally with turbid
      phantoms. Thus, this Letter may prove useful in tissue polarimetry.

PMID- 29028005
TI  - Microbiome and infectivity studies reveal complex polyspecies tree disease in
      Acute Oak Decline.
AB  - Decline-diseases are complex and becoming increasingly problematic to tree health
      globally. Acute Oak Decline (AOD) is characterized by necrotic stem lesions and
      galleries of the bark-boring beetle, Agrilus biguttatus, and represents a serious
      threat to oak. Although multiple novel bacterial species and Agrilus galleries
      are associated with AOD lesions, the causative agent(s) are unknown. The AOD
      pathosystem therefore provides an ideal model for a systems-based research
      approach to address our hypothesis that AOD lesions are caused by a polymicrobial
      complex. Here we show that three bacterial species, Brenneria goodwinii,
      Gibbsiella quercinecans and Rahnella victoriana, are consistently abundant in the
      lesion microbiome and possess virulence genes used by canonical phytopathogens
      that are expressed in AOD lesions. Individual and polyspecies inoculations on oak
      logs and trees demonstrated that B. goodwinii and G. quercinecans cause tissue
      necrosis and, in combination with A. biguttatus, produce the diagnostic symptoms
      of AOD. We have proved a polybacterial cause of AOD lesions, providing new
      insights into polymicrobial interactions and tree disease. This work presents a
      novel conceptual and methodological template for adapting Koch's postulates to
      address the role of microbial communities in disease.

PMID- 29028010
TI  - Highly sensitive demodulation of a vibration-induced phase shift based on a low
      noise OEO.
AB  - A highly sensitive demodulation approach of a vibration-induced phase shift based
      on a low-noise optoelectronic oscillator (OEO) is proposed and experimentally
      demonstrated. The vibration-induced optical phase variation is directly converted
      to the electrical oscillating signal of the OEO with carrier phase-shifted double
      sideband (CPS-DSB) modulation, which is realized by cascading a dual-output Mach
      Zehnder modulator (DOMZM) and a fiber interferometer. Theoretically, within a CPS
      DSB modulated OEO, the minimum detectable optical phase shift is determined by
      the phase noise achievable, and the sensitivity of the optical phase shift
      demodulation no longer depends on its frequency. A proof-of-concept OEO
      oscillating at 100 MHz with ultralow phase noise is built for demonstration. The
      achieved minimum detectable optical phase shift is 0.58  MUrad/?Hz at 1 kHz and
      0.21  MUrad/?Hz at 10 kHz, which are the best results ever reported, to the best
      of our knowledge.

PMID- 29028011
TI  - Mid-infrared 1  W hollow-core fiber gas laser source.
AB  - We report the characteristics of a 1 W hollow-core fiber gas laser emitting CW in
      the mid-IR. Our system is based on an acetylene-filled hollow-core optical fiber
      guiding with low losses at both the pump and laser wavelengths and operating in
      the single-pass amplified spontaneous emission regime. Through systematic
      characterization of the pump absorption and output power dependence on gas
      pressure, fiber length, and pump intensity, we determine that the reduction of
      pump absorption at high pump flux and the degradation of gain performance at high
      gas pressure necessitate the use of increased gain fiber length for efficient
      lasing at higher powers. Low fiber attenuation is therefore key to efficient high
      power laser operation. We demonstrate 1.1 W output power at a 3.1 MUm wavelength
      by using a high-power erbium-doped fiber amplifier pump in a single-pass
      configuration, approximately 400 times higher CW output power than in the ring
      cavity previously reported.

PMID- 29028012
TI  - Ultra-compact all-in-fiber-core Mach-Zehnder interferometer.
AB  - Optical Mach-Zehnder interferometers (MZIs) are useful components in a variety of
      optical applications, including optical modulation; signal processing; and
      physical, chemical, and biological sensing. We introduce here a novel, assembly
      free all-in-fiber-core MZI, which is directly written with a femtosecond laser.
      By introducing a positive refractive index-modified zone in half of the fiber
      core, the original single-mode fiber section is converted into a few-mode fiber
      section, where a strong coupling between the two lowest-order guided modes is
      generated, resulting in a well-defined interference spectrum in transmission.
      This device promises many significant advantages over existing approaches such as
      ease of fabrication, stability, small insertion loss, robustness extremely broad
      operating bandwidth, and precise and controllable cavity lengths. These
      advantages make this device strikingly attractive with the potential for
      extensive adoption in fiber communications, signal processing, sensors, and laser
      wavelength control.

PMID- 29028013
TI  - Plasmonic topological insulators for topological nanophotonics.
AB  - Photonic topological insulators are optical structures supporting robust
      propagation of light at their edges that are topologically protected from
      scattering. Here we propose the concept of plasmonic topological insulators (PTI)
      that not only topologically protect light at the lattice edges but also enable
      their confinement and guidance at the deep-subwavelength scale. The suggested PTI
      are composed of an evanescently coupled array of metallic nanowires that are
      modulated periodically along the light propagation direction. The intrinsic loss
      associated with the PTI is found not to deteriorate their topological protection
      on the edge modes. The proposed PTI may find interesting applications in
      nanophotonics, where the tolerance to the fabrication disorders for device
      applications are essential.

PMID- 29028014
TI  - Classes of non-parity-time-symmetric optical potentials with exceptional-point
      free phase transitions.
AB  - Paraxial linear propagation of light in an optical waveguide with material gain
      and loss is governed by a Schrodinger equation with a complex potential. In this
      Letter, new classes of non-parity-time (PT)-symmetric complex potentials
      featuring conjugate-pair eigenvalue symmetry are constructed by operator symmetry
      methods. Due to this eigenvalue symmetry, it is shown that the spectrum of these
      complex potentials is often all-real. Under parameter tuning in these potentials,
      a phase transition can also occur, where pairs of complex eigenvalues appear in
      the spectrum. A distinctive feature of the phase transition here is that the
      complex eigenvalues may bifurcate out from an interior continuous eigenvalue
      inside the continuous spectrum; hence, a phase transition takes place without
      going through an exceptional point. In one spatial dimension, this class of non
      PT-symmetric complex potentials is of the form V(x)=h'(x)-h2(x), where h(x) is an
      arbitrary PT-symmetric complex function. These potentials in two spatial
      dimensions are also derived. Diffraction patterns in these complex potentials are
      further examined, and unidirectional propagation behaviors are demonstrated.

PMID- 29028015
TI  - Simplified demultiplexing scheme for two PDM-IM/DD systems utilizing a single
      Stokes analyzer over 25-km SMF.
AB  - We propose a four-linear state of polarization multiplexed intensity modulation
      and direct detection (IM/DD) scheme based on two orthogonal polarization division
      multiplexing (PDM) on-off keying systems. We also experimentally demonstrate a
      simple demultiplexing algorithm for this scheme by utilizing only a single Stokes
      analyzer. At the rate of 4*10  Gbit/s, the experimental results show that the
      power penalty of the proposed scheme is about 1.5 dB, compared to the single PDM
      IM/DD for back-to-back (B2B) transmission. Compared to B2B, just about 1.7 dB
      power penalty is required after 25 km Corning LEAF optical fiber transmission.
      Meanwhile, the performance of the polarization tracking is evaluated, and the
      results show that the BER fluctuation is less than 0.5 dB with a polarization
      scrambling rate up to 708.75 deg/s.

PMID- 29028016
TI  - Measuring the electromagnetic chirality of 2D arrays under normal illumination.
AB  - We present an electromagnetic chirality measure for 2D arrays of subwavelength
      periodicities under normal illumination. The calculation of the measure uses only
      the complex reflection and transmission coefficients from the array. The measure
      allows the ordering of arrays according to their electromagnetic chirality, which
      further allows a quantitative comparison of different design strategies. The
      measure is upper bounded, and the extreme properties of objects with high values
      of electromagnetic chirality make them useful in both near- and far-field
      applications. We analyze the consequences that different possible symmetries of
      the array have on its electromagnetic chirality. We use the measure to study four
      different arrays. The results indicate the suitability of helices for building
      arrays of high electromagnetic chirality, and the low effectiveness of a
      substrate for breaking the transverse mirror symmetry.

PMID- 29028018
TI  - Solitons in a PT-symmetric chi(2) coupler.
AB  - We consider the existence and stability of solitons in a chi(2) coupler. Both the
      fundamental and second harmonics (SHs) undergo gain in one of the coupler cores
      and are absorbed in the other one. The gain and loss are balanced, creating a
      parity-time (PT) symmetric configuration. We present two types of families of PT
      symmetric solitons having equal and different profiles of the fundamental and
      SHs. It is shown that the gain and loss can stabilize solitons. The interaction
      of stable solitons is shown. In the cascading limit, the model is reduced to the
      PT-symmetric coupler with effective Kerr-type nonlinearity and the balanced
      nonlinear gain and loss.

PMID- 29028017
TI  - Arbitrary-shaped Brillouin microwave photonic filter by manipulating a directly
      modulated pump.
AB  - We present a cost-effective gigahertz-wide arbitrary-shaped microwave photonic
      filter based on stimulated Brillouin scattering in fiber using a directly
      modulated laser (DML). After analyzing the relationship between the spectral
      power density and the modulation current of the DML, we manage to precisely
      adjust the optical spectrum of the DML, thereby controlling the Brillouin filter
      response arbitrarily for the first time, to the best of our knowledge. The filter
      performance is evaluated by amplifying a 500 Mb/s non-return-to-zero on-off
      keying signal using a 1 GHz rectangular filter. The comparison between the
      proposed DML approach and the previous approach adopting a complex IQ modulator
      shows similar filter flexibility, shape fidelity, and noise performance, proving
      that the DML-based Brillouin filter technique is a cost-effective and valid
      solution for microwave photonic applications.

PMID- 29028019
TI  - Tunable spin Hall effect of light with graphene at a telecommunication
      wavelength.
AB  - The spin Hall effect of light (SHEL) has been widely studied for manipulating
      spin-polarized photons. In this Letter, we present a mechanism to tune the spin
      shift of the SHEL electrically at 1550 nm by means of introducing a graphene
      layer. The spin shift is quite sensitive to a graphene layer near the Brewster
      angle for horizontal polarization incidence and can be dynamically tuned by
      varying the Fermi energy of graphene. We find that the position of the Brewster
      angle and the value of the spin shift are decided by the real and imaginary parts
      of graphene conductivity, respectively. In addition, two different tuned regions
      have been revealed: one is the "step-like switch" region where the spin shift
      switches between two values, and the other is the "negative modulation" region
      where the spin shift declines gradually as the Fermi energy increases. These
      findings may provide a new paradigm for a tunable spin photonic device.

PMID- 29028020
TI  - Coherent solid-state LIDAR with silicon photonic optical phased arrays.
AB  - We present, to the best of our knowledge, the first demonstration of coherent
      solid-state light detection and ranging (LIDAR) using optical phased arrays in a
      silicon photonics platform. An integrated transmitting and receiving frequency
      modulated continuous-wave circuit was initially developed and tested to confirm
      on-chip ranging. Simultaneous distance and velocity measurements were performed
      using triangular frequency modulation. Transmitting and receiving optical phased
      arrays were added to the system for on-chip beam collimation, and solid-state
      beam steering and ranging measurements using this system are shown. A cascaded
      optical phase shifter architecture with multiple groups was used to simplify
      system control and allow for a compact packaged device. This system was
      fabricated within a 300 mm wafer CMOS-compatible platform and paves the way for
      disruptive low-cost and compact LIDAR on-chip technology.

PMID- 29028021
TI  - Intensity noise suppression in mode-locked fiber lasers by double optical
      bandpass filtering.
AB  - We show that the relative intensity noise (RIN) of a mode-locked fiber laser can
      be suppressed below a -140  dB/Hz level for the entire >20  Hz offset frequency
      range by a proper combination of intra-cavity and extra-cavity optical bandpass
      filters. When a 12-nm-bandwidth intra-cavity filter and a 16-nm-bandwidth extra
      cavity filter are employed for a polarization-maintaining-nonlinear-amplifying
      loop-mirror (PM-NALM)-based Er-fiber laser, the RIN spectrum level is suppressed
      by ~30  dB in the low offset frequency range. The resulting integrated rms RIN is
      only 0.0054% [1 Hz-1 MHz]-to our knowledge, one of the lowest integrated RIN
      performances for any mode-locked laser reported so far. Besides the simplicity,
      this double-filtering approach has an additional advantage: unlike active pump
      laser feedback methods, it does not have any resonant peaks in the stabilized RIN
      spectrum. In addition to the RIN suppression, with intra-cavity bandpass
      filtering, the integrated rms timing jitter is also reduced from 7.29-fs (no
      filter) to 2.95-fs (12-nm intra-cavity filter) [10 kHz-1 MHz] in the soliton PM
      NALM laser.

PMID- 29028022
TI  - Continuous tunable broadband emission of fluorphosphate glasses for single
      component multi-chromatic phosphors.
AB  - A kind of Sn2+/Mn2+ co-doped fluorphosphate (FP) glasses that served as single
      component continuous tunable broadband emitting multi-chromatic phosphors are
      developed for the first time. Importantly, these FP glasses have high thermal
      conductivity (3.25-3.70  W/m.K) and good chemical stability in water (80 degrees
      C). By combining with commercially available UV-LEDs directly, the emission
      colors can be tuned from blue/cold-white to warm-white/red through the energy
      transfer from Sn2+ to Mn2+, and the broadband spectra covering the whole visible
      region from 380 nm to 760 nm. Notably, the FP glass can also serve as a white
      light phosphor by controlling the content of SnO/MnO, which has excellent optical
      properties. The CIE chromaticity coordinate, color rendering index, and quantum
      efficiency are (0.33, 0.29), 84, and 0.952, respectively. These new phosphors,
      possessing good optical and chemical properties, are promising for applications
      in solid-state lighting devices.

PMID- 29028023
TI  - Study of femtosecond laser-induced circular optical properties in silica by
      Mueller matrix spectropolarimetry.
AB  - Transmission Mueller-matrix spectroscopic ellipsometry is applied to femtosecond
      laser-induced modifications in silica glass in the spectral range of 450-1000 nm.
      Within a type II regime, the modifications exhibit not only circular dichroism,
      but also circular birefringence. We suggest that the laser polarization
      orientation with respect to pulse front tilt determines the amplitude and the
      sign of the circular properties. By using differential decomposition of the
      Mueller matrix, optical rotation is revealed for the first time, to the best of
      our knowledge. A maximum value of the effective optical activity of 143 degrees
      /mm at 550 nm is found.

PMID- 29028024
TI  - Time-delay signature suppression in a chaotic semiconductor laser by fiber random
      grating induced random distributed feedback.
AB  - We demonstrate that a semiconductor laser perturbed by distributed feedback with
      random time delays from a large number of scattering centers along a fiber random
      grating can emit light chaotically without the time-delay signature (TDS). A
      theoretical model is developed based on the modified Lang-Kobayashi model to
      numerically explore the chaotic dynamics of the laser diode subjected to random
      feedback. It is predicted that the random distributed feedback destroys the phase
      correlated mode condition and hence suppresses the TDS. The fiber random grating
      is fabricated with random index modulation periods through point-by-point
      inscription, which introduces large numbers of phase-uncorrelated cavity modes
      into the semiconductor laser, leading to high dimensional chaotic dynamics and
      thus the concealment of the TDS. The experimentally obtained TDS value is
      negligible with a minimum of 0.0088, which is the smallest to date.

PMID- 29028025
TI  - Photoacoustic imaging methodology for the optical characterization of contact
      lenses.
AB  - We demonstrate photoacoustic microscopy as a metrology method for the optical
      characterization and quality control of contact lenses (CLs). Dual-wavelength
      excitation is applied to CLs tinted on both sides with two thin ink layers, each
      of them possessing distinctly different optical absorption properties. Thus, the
      method is capable of measuring the elevation maps of both CL surfaces during two
      subsequent imaging sessions and extracting the CL thickness, curvatures, and
      dioptric power. We show that such an easily implementable technique provides
      robust, high-precision, cost-effective three-dimensional imaging and
      characterization of both rigid and soft CLs, which renders it highly favorable
      for a broad range of applications.

PMID- 29028026
TI  - Synthesis of circularly coherent sources.
AB  - An experiment is presented in which a partially coherent source endowed with
      circular coherence is generated. The source is synthesized through a time
      averaging procedure, so that the mutual intensity is used as the basic
      correlation function. The correlation between points at different radial
      distances from the source center is tested by means of a Young interferometer. To
      confirm the perfect coherence among points along a circle concentric with the
      source center, the Young mask is replaced by an array of equally spaced pinholes
      arranged along a circle. The observed pattern is identical to that produced by
      the same mask, illuminated by perfectly coherent light.

PMID- 29028027
TI  - Fabrication of disk droplets and evaluation of their lasing action.
AB  - Disk resonators are difficult to create with droplets, since they self-form
      spheres due to the surface tension. In this study, disk (cylindrical) droplets
      were created by enclosing a dye (rhodamine 6G) solution in silicone rubber.
      Lasing actions of these droplets were examined by pulsed green laser excitation.
      In a large droplet (2 mm diameter), the whispering gallery mode emission was
      difficult to attain, since it competed with the radial or axial modes that made a
      round trip in the droplet. A disk droplet of 150 MUm diameter exhibited a comb
      like spectrum of the whispering gallery mode resonant emission.

PMID- 29028028
TI  - Enhanced total internal reflection using low-index nanolattice materials.
AB  - Low-index materials are key components in integrated photonics and can enhance
      index contrast and improve performance. Such materials can be constructed from
      porous materials, which generally lack mechanical strength and are difficult to
      integrate. Here we demonstrate enhanced total internal reflection (TIR) induced
      by integrating robust nanolattice materials with periodic architectures between
      high-index media. The transmission measurement from the multilayer stack
      illustrates a cutoff at about a 60 degrees  incidence angle, indicating an
      enhanced light trapping effect through TIR. Light propagation in the nanolattice
      material is simulated using rigorous coupled-wave analysis and transfer matrix
      methods, which agrees well with experimental data. The demonstration of the TIR
      effect in this Letter serves as a first step towards the realization of
      multilayer devices with nanolattice materials as robust low-index components.
      These nanolattice materials can find applications in integrated photonics,
      antireflection coatings, photonic crystals, and low-k dielectric.

PMID- 29028029
TI  - Flat-top narrowband filters enabled by guided-mode resonance in two-level
      waveguides.
AB  - Resonant nanogratings and periodic metasurfaces express diverse spectral and
      polarization properties on broadside illumination by incident light. Cooperative
      resonance interactions may yield shaped spectra for particular applications, in
      contrast to a multilayer dielectric mirror. Here, we provide guided-mode
      resonance filters with flat-top spectra suitable for wavelength division
      multiplexing systems. Applying a single one-dimensional grating layer sandwiched
      by two waveguides, we theoretically achieve high-efficiency flat-top spectra in
      the near-infrared region. This result is obtained by inducing simultaneous nearly
      degenerate resonant modes. The resonance separation under this condition controls
      the width of the flat-top spectrum. This means we can implement spectral widths
      ranging from a sub-nanometer to several nanometers applying fundamentally the
      same device architecture.

PMID- 29028030
TI  - Mode selecting switch using multimode interference for on-chip optical
      interconnects.
AB  - A novel mode selecting switch (MSS) is experimentally demonstrated for on-chip
      mode-division multiplexing (MDM) optical interconnects. The MSS consists of a
      Mach-Zehnder interferometer with tapered multi-mode interference couplers and TiN
      thermo-optic phase shifters for conversion and switching between the optical data
      encoded on the fundamental and first-order quasi-transverse electric (TE) modes.
      The C-band MSS exhibits a >25  dB switching extinction ratio and < -12 dB
      crosstalk. We validate the dynamic switching with a 25.8 kHz gating signal
      measuring switching times for both TE0 and TE1 modes of <10.9  MUs. All channels
      exhibit less than 1.7 dB power penalty at a 10-12 bit error rate, while switching
      the non-return-to-zero PRBS-31 data signals at 10  Gb/s.

PMID- 29028031
TI  - Precise identification of graphene layers at the air-prism interface via a pseudo
      Brewster angle.
AB  - We propose a simple method for the precise identification of graphene layers at
      the air-prism interface via a pseudo-Brewster angle, where the horizontally
      polarized reflection is close to zero. We find that the pseudo-Brewster angle is
      sensitive to the variation of graphene layers where the pseudo-Brewster angle is
      approximately linearly increased about 0.5 deg as the layer numbers increased.
      Furthermore, the sensitivity of the pseudo-Brewster angle can be greatly enhanced
      and reaches 0.04 deg by eliminating the influence of the cross-polarization
      effect. Our scheme can provide a simple and effective method to identify the
      layer numbers of graphene.

PMID- 29028032
TI  - Proof-of-principle implementation of a quantum random number generator with
      independent devices and a dimension witness.
AB  - The random number is a paramount issue in modern science. How to estimate the
      genuine randomness of the data generated by a given device is a central problem.
      Lunghi et al. proposed a self-testing quantum random number generator from a
      prepare-and-measure scenario with independent devices. Based on this Letter, Han
      et al. proposed a more efficient method (Han16 protocol for short) to estimate
      the genuine randomness. Here we report a proof-of-principle realization of the
      Han16 protocol with a HSPS. The experimental results demonstrate that the Han16
      protocol almost doubles the generation rate of the quantum random number with
      regard to the previous protocol. In addition, the results of the experiment show
      that the Han16 protocol is practical, and the experimental device can tolerate
      loss and noise.

PMID- 29028033
TI  - Flat top surface plasmon polariton beams.
AB  - Surface plasmon polaritons (SPPs) have emerged as powerful tools for guiding and
      manipulating light below the diffraction limit. In this context, the availability
      of flat top SPP beams displaying a constant transversal profile can allow for
      uniform excitation and coupling scenarios, thus opening the door to developing
      novel applications that cannot be achieved using conventional Gaussian SPP beams.
      Here, we present a rigorous theoretical description of flat top SPP beams
      propagating along flat metal-dielectric interfaces. This is accomplished through
      the use of Hermite-Gaussian SPP modes that constitute a complete basis set for
      the solutions of Maxwell's equations for a metal-dielectric interface in the
      paraxial approximation. We provide a comprehensive analysis of the evolution of
      the transversal profiles of these beams as they propagate, which is complemented
      with the study of the width and kurtosis parameters. Our results serve to enlarge
      the capabilities of surface plasmon polaritons to control and manipulate light
      below the diffraction limit.

PMID- 29028034
TI  - Soliton trapping and comb self-referencing in a single microresonator with chi(2)
      and chi(3) nonlinearities.
AB  - A shaped doublet pump pulse is proposed for a simultaneous octave-spanning
      soliton Kerr frequency comb generation and second-harmonic conversion in a single
      microresonator. The temporal soliton in the cavity is trapped atop a doublet
      pulse pedestal, resulting in a greatly expanded soliton region compared to that
      with a general Gaussian pulse pump. The possibility of single-microresonator comb
      self-referencing in a single silicon nitride microring that can facilitate
      compact on-chip optical clocks is demonstrated via simulation.

PMID- 29028035
TI  - Generation, amplification, frequency conversion, and reversal of propagation of
      THz photons in nonlinear hyperbolic metamaterial.
AB  - We propose metamaterial (MM) that supports a mixture of three or more normal and
      backward electromagnetic modes with equal co-directed phase velocities and
      mutually contra-directed energy fluxes. This enables extraordinary three-wave
      mixing, greatly enhanced optical parametric amplification, and frequency-changing
      generation of entangled photons in the reflection direction. Proof-of-principle
      numerical simulation of such processes is presented based on the particular
      example of the wave-guided terahertz waves contra-propagating in the MM made of
      carbon nanotubes.

PMID- 29028036
TI  - Synthesis and characterization of depolarizing samples based on the indices of
      polarimetric purity.
AB  - In this work, we discuss the interest of using the indices of polarimetric purity
      (IPPs) as a criterion for the characterization and classification of depolarizing
      samples. We prove how differences in the depolarizing capability of samples, not
      seen by the commonly used depolarization index PDelta, are identified by the
      IPPs. The above-stated result is analyzed from a theoretical point of view and
      experimentally verified through a set of polarimetric measurements. We show how
      the approach presented here can be useful in easily synthetizing depolarizing
      samples with controlled depolarizing features, just by properly combining low
      cost fully polarizing elements (such as linear retarders or polarizers).

PMID- 29028037
TI  - Hopping induced inversions and Pancharatnam excursions of C-points.
AB  - In this Letter, we show the acquisition of the Pancharatnam phase by a C-point
      singularity when it is subjected to discrete cyclic polarization transformations.
      The changes in state of polarizations (SOPs) are mapped onto a Poincare sphere as
      geodesical closed trajectories. The Pancharatnam phase acquired by a C-point is
      equal to the solid angle subtended by the closed trajectories at the center of
      the Poincare sphere. We show this by considering index hopping induced inversions
      of C-points. For example, a lemon from the North Pole of a Poincare sphere is
      first converted into a star whose location can be traced to the South Pole of the
      Poincare sphere and retrieved back as a lemon at the North Pole to complete a
      closed geodesical trajectory on the Poincare sphere. Depending on the trajectory,
      it is shown that the lemons (stars) acquire different amounts of the Pancharatnam
      phase, attributable to the amount of rotation in the SOP pattern of the lemons
      (stars).

PMID- 29028038
TI  - Hybrid optical pumping of K and Rb atoms in a paraffin coated vapor cell.
AB  - Dynamic hybrid optical pumping effects with a radio-frequency field-driven
      nonlinear magneto-optical rotation scheme are studied in a dual-species paraffin
      coated vapor cell. By pumping K atoms and probing Rb87 atoms, we achieve an
      intrinsic magnetic resonance linewidth of 3 Hz, and the observed resonance is
      immune to power broadening and light-shift effects. Such an operation scheme
      shows favorable prospects for atomic magnetometry applications.

PMID- 29028039
TI  - Vertically integrated spot-size converter in AlGaAs-GaAs.
AB  - We report on the demonstration of a spot size converter (SSC) for monolithic
      photonic integration at a wavelength of 850 nm on a GaAs substrate. We designed
      and fabricated a dual-waveguide AlGaAs chip. The design consists of a lower
      waveguide layer for efficient end-fire coupling to a single-mode fiber, an upper
      waveguide layer for high refractive index contrast waveguides, and a vertical SSC
      to connect the two waveguide layers. We measured a SSC conversion efficiency of
      91% (or -0.4  dB) between the upper and lower waveguide layers for the TE mode at
      a wavelength of 850 nm.

PMID- 29028040
TI  - Ex vivo validation of photo-magnetic imaging.
AB  - We recently introduced a new high-resolution diffuse optical imaging technique
      termed photo-magnetic imaging (PMI), which utilizes magnetic resonance
      thermometry (MRT) to monitor the 3D temperature distribution induced in a medium
      illuminated with a near-infrared light. The spatiotemporal temperature
      distribution due to light absorption can be accurately estimated using a combined
      photon propagation and heat diffusion model. High-resolution optical absorption
      images are then obtained by iteratively minimizing the error between the measured
      and modeled temperature distributions. We have previously demonstrated the
      feasibility of PMI with experimental studies using tissue simulating agarose
      phantoms. In this Letter, we present the preliminary ex vivo PMI results obtained
      with a chicken breast sample. Similarly to the results obtained on phantoms, the
      reconstructed images reveal that PMI can quantitatively resolve an inclusion with
      a 3 mm diameter embedded deep in a biological tissue sample with only 10% error.
      These encouraging results demonstrate the high performance of PMI in ex vivo
      biological tissue and its potential for in vivo imaging.

PMID- 29028041
TI  - Comparing mode-crosstalk and mode-dependent loss of laterally displaced orbital
      angular momentum and Hermite-Gaussian modes for free-space optical communication.
AB  - There is interest in using orbital angular momentum (OAM) modes to increase the
      data speed of free-space optical communication. A prevalent challenge is the
      mitigation of mode-crosstalk and mode-dependent loss that is caused by the modes'
      lateral displacement at the data receiver. Here, the mode-crosstalk and mode
      dependent loss of laterally displaced OAM modes (LG0,+1, LG0,-1) are
      experimentally compared to that of a Hermite-Gaussian (HG) mode subset (HG0,1,
      HG1,0). It is shown, for an aperture larger than the modes' waist sizes, some of
      the HG modes can experience less mode-crosstalk and mode-dependent loss when
      laterally displaced along a symmetry axis. It is also shown, over a normal
      distribution of lateral displacements whose standard deviation is 2* the modes'
      waist sizes, on average, the HG modes experience 66% less mode-crosstalk and 17%
      less mode-dependent loss.

PMID- 29028042
TI  - Nonlinear pulse compression to 43  W GW-class few-cycle pulses at 2  MUm
      wavelength.
AB  - High-average power laser sources delivering intense few-cycle pulses in
      wavelength regions beyond the near infrared are promising tools for driving the
      next generation of high-flux strong-field experiments. In this work, we report on
      nonlinear pulse compression to 34.4 MUJ-, 2.1-cycle pulses with 1.4 GW peak power
      at a central wavelength of 1.82 MUm and an average power of 43 W. This
      performance level was enabled by the combination of a high-repetition-rate
      ultrafast thulium-doped fiber laser system and a gas-filled antiresonant hollow
      core fiber.

PMID- 29028043
TI  - Dual fluorescence-absorption deconvolution applied to extended-depth-of-field
      microscopy.
AB  - Fast imaging over large volumes can be obtained in a simple manner with extended
      depth-of-field (EDOF) microscopy. A standard technique of Wiener deconvolution
      can correct for the blurring inherent in EDOF images. We compare Wiener
      deconvolution with an alternative, parameter-free technique based on the dual
      reconstruction of fluorescence and absorption layers in a sample. This
      alternative technique provides significantly enhanced reconstruction contrast
      owing to a quadratic positivity constraint that intrinsically favors sparse
      solutions. We demonstrate the advantages of this technique with mouse neuronal
      images acquired in vivo.

PMID- 29028044
TI  - Field extension inside guided-mode-resonance filters under a focused beam.
AB  - We present a theoretical study of the mid-infrared guided mode resonance spectral
      filters made of two subwavelength metallic gratings and a dielectric waveguide
      under a focused beam with a finite spot size. This Letter shows that, at the
      resonant wavelength, the lateral extension of the electromagnetic field in the
      waveguide is close to the width of the beam. We compare the performance of
      filters using gratings with a one-slit pattern and gratings with a two-slit
      pattern, and we show that the latter gratings (biatom gratings) provide a higher
      transmission and a better limitation of field extension, due to an improved
      angular acceptance. These results open new perspectives for pixel-sized infrared
      filters.

PMID- 29028045
TI  - LED-pumped alexandrite laser oscillator and amplifier.
AB  - Taking advantage of light-emitting-diode (LED) performance breakthrough driven by
      the lighting market, we report, to the best of our knowledge, the first LED
      pumped chromium-doped crystal laser oscillator and amplifier based on alexandrite
      crystals (Cr3+:BeAl2O4). We developed a Ce:YAG concentrator as the pumped source,
      illuminated by blue LEDs that can be easily power scaled. With 2200 LEDs (450
      nm), the Ce:YAG concentrator can deliver to the gain medium up to 268 mJ at 10 Hz
      at 550 nm with a irradiance of 8.5  kW/cm2. We demonstrate, in oscillator
      configuration, an LED-pumped alexandrite laser delivering an energy of 2.9 mJ at
      748 nm in free running operation. In the cavity, we measured a double-pass small
      signal gain of 1.28, which is in good agreement with numerical simulations. As an
      amplifier, the system demonstrated to boost a CW Ti:sapphire laser by a factor of
      4 at 750 nm in eight passes with a large tuning range from 710 nm to 800 nm.

PMID- 29028046
TI  - On the manifestation of higher-order nonlinearities in a noble gas medium
      undergoing strong ionization.
AB  - While there is a consensus that higher-order effects beyond chi(3) are present
      also in high-intensity light-matter interactions, when and how they become
      apparent needs further study. The central question addressed in this Letter is
      whether it is possible to design a situation in which they show up before being
      completely masked by the electrons freed by a high-intensity field. The second
      question we attempt to answer is how much such observations, if and when
      feasible, can reveal about the nature of the nonlinear polarization. We answer
      the first question in the affirmative, but our comparative simulations indicate
      that distinguishing the higher-order nonlinearity from the third-order
      polarization can be extremely challenging. We also briefly discuss the
      implications for the interpretation of the measured values of the nonlinear
      index.

PMID- 29028047
TI  - Chip-scale nanophotonic switch based on a waveguide-metamaterial coupling
      mechanism.
AB  - We demonstrate a simple and effective waveguide-metamaterial coupling mechanism
      to achieve switching control of the fundamental TE mode propagation in a silicon
      photonic stripe waveguide. The metamaterial is made of vertically stacked
      alternating ITO/Si layers and, theoretically, can be switched between transparent
      and absorptive regimes via modifying the carrier concentration of the ITO layers.
      In addition to its small footprint and CMOS-compatible fabrication, simulation
      results indicate that the optical switch features a high modulation depth (MD) of
      27.8 dB, low insertion losses of 0.004 dB, and a wide operating bandwidth of 300
      nm where the MD is >24.6  dB. We expect that this mechanism is a good candidate
      for designing high-performance and ultra-compact photonic devices in densely
      integrated nanophotonic circuits and computation systems.

PMID- 29028048
TI  - Fine-structure oscillations of noise-like pulses induced by amplitude modulation
      of nonlinear polarization rotation.
AB  - The generation and evolution processes of noise-like pulses (NLPs) in an all
      normal-dispersion nonlinear polarization rotation (NPR) mode-locked Yb-doped
      fiber laser are numerically and experimentally investigated. We demonstrate that
      the amplitude modulation induced by reverse saturable absorption and the peak
      power-limiting effect of the NPR plays a key role in the formation of fine
      structure oscillations of NLPs. The width variation of the NLPs is also discussed
      in detail.

PMID- 29028049
TI  - Open-cavity fiber laser with distributed feedback based on externally or self
      induced dynamic gratings.
AB  - Dynamic population inversion gratings induced in an active medium by counter
      propagating optical fields may have a reverse effect on writing laser radiation
      via feedback they provide. In this Letter we report, to the best of our
      knowledge, on the first demonstration of an open-cavity fiber laser in which the
      distributed feedback is provided by a dynamic grating "written" in a Yb-doped
      active fiber, either by an external source or self-induced via a weak (~0.1%)
      reflection from an angle-cleaved fiber end. It has been shown that meters-long
      dynamic grating is formed with a narrow bandwidth (<50  MHz) and a relatively
      high-reflection coefficient (>7%) securing single-frequency operation, but the
      subsequent hole-burning effects accompanied by new grating formation lead to the
      switching from one longitudinal mode to another. providing a regular pulse-mode
      dynamics. As a result, periodically generated pulse trains cover a spectrum range
      of several terahertz delivering millions of cavity modes in sequent pulses.

PMID- 29028050
TI  - Performance optimization of PM-16QAM transmission system enabled by real-time
      self-adaptive coding.
AB  - We experimentally demonstrate self-adaptive coded 5*100  Gb/s WDM polarization
      multiplexed 16 quadrature amplitude modulation transmission over a 100 km fiber
      link, which is enabled by a real-time control plane. The real-time optical signal
      to-noise ratio (OSNR) is measured using an optical performance monitoring device.
      The OSNR measurement is processed and fed back using control plane logic and
      messaging to the transmitter side for code adaptation, where the binary data are
      adaptively encoded with three types of low-density parity-check (LDPC) codes with
      code rates of 0.8, 0.75, and 0.7 of large girth. The total code-adaptation
      latency is measured to be 2273 ms. Compared with transmission without adaptation,
      average net capacity improvements of 102%, 36%, and 7.5% are obtained,
      respectively, by adaptive LDPC coding.

PMID- 29028051
TI  - Flexible femtosecond inscription of fiber Bragg gratings by an optimized
      deformable mirror.
AB  - The period of fiber Bragg gratings is adapted by shaping the wavefronts of
      ultrashort laser pulses applied in a phase mask inscription technique. A
      specially designed deformable mirror, based on a dielectric substrate to
      withstand high peak powers, is utilized to deform the wavefront. A shift of about
      11 nm is demonstrated for a Bragg wavelength around 1550 nm.

PMID- 29028052
TI  - Point-by-point fabrication and characterization of sapphire fiber Bragg gratings.
AB  - The Letter reports the inscription of fiber Bragg gratings (FBGs) in a single
      crystal sapphire optical fiber via a point-by-point method by 780 nm infrared
      femtosecond laser pulses. Compared to phase mask exposure, the use of the point
      by-point method for the inscription provides a flexible way to fabricate sapphire
      FBGs and to make wavelength division multiplexing in sapphire fiber more
      practicable. The multiplexing of three cascade gratings is demonstrated, and
      their performance up to 1400 degrees C is tested. The permanent enhancement of
      reflectivity by a factor of about 5 after heat treatment and the nearly linear
      temperature response with a slope of 25.8 pm/ degrees C are demonstrated.

PMID- 29028053
TI  - Subwavelength dielectric nanorod chains for energy transfer in the visible range.
AB  - We report a new type of energy transfer device, formed by a dielectric nanorod
      array embedded in a silver slab. Such dielectric chain structures allow surface
      plasmon wave guiding with large propagation length and highly suppressed
      crosstalk between adjacent transmission channels. The simulation results show
      that our proposed design can be used to enhance the energy transfer along the
      waveguide-like dielectric nanorod chains via coupled plasmons, where the energy
      spreading is effectively suppressed, and superior imaging properties in terms of
      resolution and energy transfer distance can be achieved.

PMID- 29028054
TI  - Extended 9.7  nm tuning range in a MOPA system with a tunable dual grating Y
      branch laser.
AB  - In this Letter, we present a tunable Y-branch hybrid master oscillator power
      amplifier (MOPA) with 5.5 W output power, emitting between 973.7 and 983.4 nm.
      The MO is a monolithic Y-branch distributed Bragg reflector (DBR) diode laser,
      which is collimated and coupled into a tapered amplifier using cylindrical
      microlenses in a compact 25  mm*25  mm conduction cooled laser package. The
      wavelength spacing between the two laser branches is 2.2 nm. Each branch can be
      electrically tuned by up to 7.5 nm of quasi-continuous wavelength tuning, which
      in combination covers up to 9.7 nm of spectral range. Over this range, an output
      power variation of 0.5% and 0.2% is observed for the left and right arms,
      respectively, while maintaining a spectral width of less than 17 pm. In addition,
      the MOPA system can be operated as a dual-wavelength system by operating both
      branches simultaneously. The presented device is suitable for nonlinear frequency
      conversion applications.

PMID- 29028055
TI  - Laser-written polarizing directional coupler with reduced interaction length.
AB  - Integrated optical waveguides, manufactured with femtosecond laser writing (FSLW)
      technology, enable precise control and manipulation of light in complicated
      photonic chips. However, due to the intrinsically low anisotropy of FSLW
      waveguides, polarizing integrated devices have had a relatively large footprint.
      In this Letter, we demonstrate an approach based on stress-induced anisotropy,
      allowing us to decrease the size of polarizing directional couplers down to 3.7
      mm, almost an order of magnitude shorter than previously reported. The measured
      extinction ratios at the wavelength of 808 nm are 16 dB and 20 dB for the
      horizontal and vertical polarizations, respectively. We provide a possible
      theoretical model for the observed effects.

PMID- 29028056
TI  - Coupled-resonator-induced plasmonic bandgaps.
AB  - By drawing an analogy with the conventional photonic crystals, the plasmonic
      bandgaps have mainly employed the periodic metallic structures, named as
      plasmonic crystals. However, the sizes of the plasmonic crystals are much larger
      than the wavelengths, and the large sizes considerably decrease the density of
      the photonic integration circuits. Here, based on the coupled-resonator effect,
      the plasmonic bandgaps are experimentally realized in the subwavelength waveguide
      resonator structure, which considerably decreases the structure size to
      subwavelength scales. An analytic model and the phase analysis are established to
      explain this phenomenon. Both the experiment and simulation show that the
      plasmonic bandgap structure has large fabrication tolerances (>20%). Instead of
      the periodic metallic structures in the bulky plasmonic crystals, the utilization
      of the subwavelength plasmonic waveguide-resonator structure not only
      significantly shrinks the bandgap structure to be about lambda2/13, but also
      expands the physics of the plasmonic bandgaps. The subwavelength dimension,
      together with the waveguide configuration and robust realization, makes the
      bandgap structure easy to be highly integrated on chips.

PMID- 29028057
TI  - Exploring the coherent interaction in a hybrid system of hollow gold nanoprisms
      and cyanine dye J-aggregates: role of plasmon-hybridization mediated local
      electric-field enhancement.
AB  - In this work, we probed the possibility of observing strong plasmon-exciton
      interactions in hollow gold nanoprism-J-aggregate nanocomposites. Several
      different hollow gold nanoprisms (HGNs) with different aspect ratios were
      synthesized. This allowed us to systematically tune the LSPR energies through the
      exciton energy of the PIC-J-aggregate, which in turn allowed us to have direct
      determination of the coupling strength of HGN-J-aggregate composites. Hybrid
      nanosystems were prepared by adsorbing and assembling 1,1'-diethyl-2,2'-cyanine
      (pseudoisocyanine or PIC) iodide onto the surface of hollow gold nanoprisms.
      Plasmon-exciton interactions were studied using extinction spectroscopy. The
      experimental results were analysed, and complemented by the results obtained from
      numerical simulations. Our results reveal that the HGN-PIC-J-aggregate hybrid
      nanosystem shows coherent coupling between the localized surface plasmons of the
      HGN and excitons of the PIC-J-aggregate, as obvious from the observation of a
      clear transparency dip and the formation of two new hybrid plexcitonic modes in
      the plexcitonic spectra. Anti-crossing behaviour of the plexcitonic modes,
      together with large Rabi splitting and coupling constant, asserts strong coupling
      between the plasmon and the exciton, overwhelming the decoherence effects, in our
      hybrid nanosystem. Analysis of the calculated near-field distribution establishes
      that the plasmon-hybridization mediated large electric-field enhancement holds
      the key to the strong coupling.

PMID- 29028058
TI  - Protein-protein interaction networks as a new perspective to evaluate distinct
      functional roles of voltage-dependent anion channel isoforms.
AB  - Voltage-dependent anion channels (VDACs) are a family of three mitochondrial
      porins and the most abundant integral membrane proteins of the mitochondrial
      outer membrane (MOM). VDACs are known to be involved in metabolite/ion transport
      across the MOM and in many cellular processes ranging from mitochondria-mediated
      apoptosis to the control of energy metabolism, by interacting with cytosolic,
      mitochondrial and cytoskeletal proteins and other membrane channels. Despite
      redundancy and compensatory mechanisms among VDAC isoforms, they display not only
      different channel properties and protein expression levels, but also distinct
      protein partners. Here, we review the known protein interactions for each VDAC
      isoform in order to shed light on their peculiar roles in physiological and
      pathological conditions. As proteins associated with the MOM, VDAC
      opening/closure as a metabolic checkpoint is regulated by protein-protein
      interactions, and is of pharmacological interest in pathological conditions such
      as cancer. The interactions involving VDAC1 have been characterized more in depth
      than those involving VDAC2 and VDAC3. Nevertheless, the so far explored VDAC
      protein interactions for each isoform show that VDAC1 is mainly involved in the
      maintenance of cellular homeostasis and in pro-apoptotic processes, whereas VDAC2
      displays an anti-apoptotic role. Despite there being limited information on
      VDAC3, this isoform could contribute to mitochondrial protein quality control and
      act as a marker of oxidative status. In pathological conditions, namely
      neurodegenerative and cardiovascular diseases, both VDAC1 and VDAC2 establish
      abnormal interactions aimed to counteract the mitochondrial dysfunction which
      contributes to end-organ damage.

PMID- 29028059
TI  - A series of organic-inorganic hybrid compounds formed by [P2W18O62]6- and several
      types of transition metal complexes.
AB  - Five new organic-inorganic hybrid compounds based on [P2W18O62]6- (abbreviated as
      {P2W18}) and several types of transition metal complexes (TMCs) have been
      synthesized and characterized by IR, UV-Vis, XRD, cyclic voltammetry measurements
      and single crystal X-ray diffraction analysis.
      [Cu(phen)2][Cu(phen)(H2O)3][Cu(phen)2(H2O)][P2W18O62].8H2O (1) (phen = 1,10
      phenanthroline) is a {P2W18} bi-supported complex of phen, while [Cu(2,2'
      bpy)(H2O)2]2[Cu(2,2'-bpy)2][P2W18O62].3.5H2O (2) (2,2'-bpy = 2,2'-bipyridine) is
      a 1-D chain structure formed by {P2W18} and copper complexes of 2,2'-bpy.
      [Ag(2,2'-bpy)2]5[HP2W18O62].H2O (3), [Ag(2,2'-bpy)(H2O)]2[Ag(2,2'-bpy)]2[Ag2(2,2'
      bpy)3][P2W18O62] (4), and [Ag(2,2'-bpy)(H2O)]3[Ag2(2,2'-bpy)3][Ag(2,2'
      bpy)][P2W18O62].H2O (5) are constructed from {P2W18} and silver complexes of 2,2'
      bpy. Compounds 4 and 5 are novel dimers of {P2W18} joined by silver complexes,
      while compound 3 contains two different kinds of silver complexes, forming a
      novel supramolecular structure. Each of the five compounds is formed by {P2W18}
      and more than one type of TMC. The formation mechanism of these compounds has
      been carefully discussed. In addition, we also synthesized two supramolecular
      structures based on {P2W18} and organic moieties: [H6P2W18O62](phen)5.5 (6) and
      [H6P2W18O62](phen)3.43H2O (7). The catalytic properties of these compounds were
      also tested.

PMID- 29028060
TI  - Molecular emulsions: from charge order to domain order.
AB  - Aqueous mixtures of small molecules, such as lower n-alkanols for example, are
      known to be micro-segregated, with domains in the nano-meter range. One
      consequence of this micro-segregation would be the existence of long range domain
      domain oscillatory correlations in the various atom-atom pair correlation
      functions, and subsequent pre-peaks in the corresponding atom-atom structure
      factors, in the q-vector range corresponding to nano-sized domains. However, no
      such pre-peak have ever been observed in the large corpus of radiation scattering
      data published so far on aqueous mixtures of small n-alkanols. By using large
      scale simulations of aqueous-1propanol mixtures, it is shown herein that the
      origin for the absence of scattering pre-peak resides in the exact cancellation
      of the contributions of the various atom-atom correlation pre-peaks to the total
      scattered intensity. The mechanism for this cancellation is due to the
      differences in the long range oscillatory behaviour of the correlations (beyond 1
      nm), which are exactly out-of-phase between same species and cross species. This
      is similar to the charge order observed in ionic melts, but differs from room
      temperature ionic liquids, where the segregation is between charged and neutral
      groups, instead of species segregation. The consequences of such cancellation in
      the experimental scattering data are examined, in relation to the possibility of
      detecting micro-segregation through such methods. In the particular case of
      aqueous-1propanol mixtures, it is shown the X-ray scattering leads an exact
      cancellation, while this cancellation in neutron scattering is seen to depend on
      the deuteration ratio between solvent and solute.

PMID- 29028061
TI  - Interaction with prefibrillar species and amyloid-like fibrils changes the
      stiffness of lipid bilayers.
AB  - Evaluating the toxicity of self-assembled protein states is a key step towards
      developing effective strategies against amyloidogenic pathologies such as
      Alzheimer's and Parkinson's diseases. Such analysis is directly connected to
      quantitatively probing the stability of the cellular membrane upon interaction
      with different protein states. Using a combination of spectroscopic techniques,
      morphological observations, and spectral analysis of membrane fluctuations, we
      identify different destabilisation routes for giant unilamellar vesicles
      interacting with native-like states, prefibrillar species and amyloid-like
      fibrils of alpha-lactalbumin. These effects range from substantially lowering the
      bending rigidity of the membranes to irreversible structural changes and complete
      disruption of the lipid bilayers. Our findings clearly indicate how the wide
      heterogeneity in structures occurring during protein aggregation can result in
      different destabilisation pathways, acting on different length scales and not
      limited to enhanced membrane permeability.

PMID- 29028062
TI  - Residual stresses in colloidal gels.
AB  - A combination of experiments and Brownian Dynamics (BD) simulations is utilized
      to examine internal stresses in colloidal gels brought to rest from steady shear
      at different shear rates. A model colloidal gel with intermediate volume fraction
      is chosen where attractions between particles are introduced by adding non
      adsorbing linear polymer chains. After flow cessation, the gel releases the
      stress in two distinct patterns: at high shear rates, where shear forces dominate
      over attractive forces, the shear-melted gel behaves as a liquid and releases
      stresses to zero after flow cessation. After low shear rates, though, stresses
      relax only partially, similar to the response of hard sphere glasses and jammed
      soft particles. The balance between shear and attractive forces which determines
      the intensity of structural distortion controls the amplitude of the residual
      stresses through a universal scaling. Stress decomposition to repulsive and
      attractive contributions in BD simulations reveals that internal stresses mainly
      originate from attractive forces. Moreover, analysis of particle dynamics
      indicates that internal stresses are associated with sub-diffusive particle
      displacements on average smaller than the attraction range as such short-range
      displacements are not sufficient to completely erase structural anisotropy caused
      during the course of shear.

PMID- 29028063
TI  - Particle formation and growth from oxalic acid, methanesulfonic acid,
      trimethylamine and water: a combined experimental and theoretical study.
AB  - Atmospheric particles influence visibility, health and climate but the mechanisms
      of their formation from initial clusters and their growth to detectable particles
      remain largely unknown. Previous studies show that reactions of methanesulfonic
      acid (MSA) with ammonia and amines form particles, a process which is enhanced by
      water. We report here results from a combined experimental-theoretical
      investigation of the effect of oxalic acid (OxA) on particle formation and growth
      from the reaction of MSA with trimethylamine (TMA) in the absence and presence of
      water. The gas phase reactants were mixed in an aerosol flow reactor (1 atm, 294
      K). Particle number concentrations and size distributions were measured as a
      function of reaction time from 0.8-12 s. The interaction of OxA with TMA with and
      without water does not lead to significant particle formation. When OxA is
      present during the reaction of MSA with TMA, there is little change (<=2 times
      more) in the particle number concentration but particles are larger compared to
      the base case of MSA with TMA alone. However, the presence of water with MSA and
      TMA overwhelms the effect of OxA so that OxA has no significant impact on
      particle number concentration or size. Results of these experiments suggest the
      MSA hydrate is important for particle formation and growth of the four component
      OxA-MSA-TMA-H2O system. These results are compared to earlier studies of the
      effect of OxA on the MSA-methylamine reaction and interpreted based on
      theoretically calculated properties of small clusters of the components.

PMID- 29028064
TI  - Nonequilibrium mode-coupling theory for dense active systems of self-propelled
      particles.
AB  - The physics of active systems of self-propelled particles, in the regime of a
      dense liquid state, is an open puzzle of great current interest, both for
      statistical physics and because such systems appear in many biological contexts.
      We develop a nonequilibrium mode-coupling theory (MCT) for such systems, where
      activity is included as a colored noise with the particles having a self
      propulsion force f0 and a persistence time taup. Using the extended MCT and a
      generalized fluctuation-dissipation theorem, we calculate the effective
      temperature Teff of the active fluid. The nonequilibrium nature of the systems is
      manifested through a time-dependent Teff that approaches a constant in the long
      time limit, which depends on the activity parameters f0 and taup. We find,
      phenomenologically, that this long-time limit is captured by the potential energy
      of a single, trapped active particle (STAP). Through a scaling analysis close to
      the MCT glass transition point, we show that taualpha, the alpha-relaxation time,
      behaves as taualpha ~ f0-2gamma, where gamma = 1.74 is the MCT exponent for the
      passive system. taualpha may increase or decrease as a function of taup depending
      on the type of active force correlations, but the behavior is always governed by
      the same value of the exponent gamma. Comparison with the numerical solution of
      the nonequilibrium MCT and simulation results give excellent agreement with
      scaling analysis.

PMID- 29028065
TI  - A Bayesian approach for estimating protein-protein interactions by integrating
      structural and non-structural biological data.
AB  - Accurate elucidation of genome wide protein-protein interactions is crucial for
      understanding the regulatory processes of the cell. High-throughput techniques,
      such as the yeast-2-hybrid (Y2H) assay, co-immunoprecipitation (co-IP), mass
      spectrometric (MS) protein complex identification, affinity purification (AP)
      etc., are generally relied upon to determine protein interactions. Unfortunately,
      each type of method is inherently subject to different types of noise and results
      in false positive interactions. On the other hand, precise understanding of
      proteins, especially knowledge of their functional associations is necessary for
      understanding how complex molecular machines function. To solve this problem,
      computational techniques are generally relied upon to precisely predict protein
      interactions. In this work, we present a novel method that combines structural
      and non-structural biological data to precisely predict protein interactions. The
      conceptual novelty of our approach lies in identifying and precisely associating
      biological information that provides substantial interaction clues. Our model
      combines structural and non-structural information using Bayesian statistics to
      calculate the likelihood of each interaction. The proposed model is tested on
      Saccharomyces cerevisiae's interactions extracted from the DIP and IntAct
      databases and provides substantial improvements in terms of accuracy, precision,
      recall and F1 score, as compared with the most widely used related state-of-the
      art techniques.

PMID- 29028066
TI  - Complex molecular surfaces and interfaces: concluding remarks.
AB  - This paper is derived from our concluding remarks presentation and the ensuing
      conversations at the Faraday Discussions meeting on Complex Molecular Surfaces
      and Interfaces, Sheffield, UK, 24th-26th July 2017. This meeting was comprised of
      sessions on understanding the interaction of molecules with surfaces and their
      subsequent organisation, reactivity or properties from both experimental and
      theoretical perspectives. This paper attempts to put these presentations in the
      wider context and focuses on topics that were debated during the meeting and
      where we feel that opportunities lie for the future development of this
      interdisciplinary research area.

PMID- 29028067
TI  - Quantum chemical and molecular dynamics modelling of hydroxylated polybrominated
      diphenyl ethers.
AB  - A series of 19 hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been
      studied using density functional theory (DFT) and molecular dynamics simulations
      with the purpose of investigating eventual correlations between their
      physicochemical properties and toxic action. Dissociation constants (pKa),
      solvation free energies and octanol-water partition coefficients (log P) have
      been computed. Additionally, metadynamics simulations of OH-PBDEs passing through
      a lipid bilayer have been carried out for four OH-PBDE species. No correlations
      between computed pKa values and toxicity data have been found. Medium
      correlations were found between partition coefficients and the ability of OH
      PBDEs to alter membrane potential in cell cultures, which is attributed to higher
      uptake of molecules with larger log P parameters. It was also demonstrated that
      in lipid bilayers, OH-PBDE molecules differ in their orientational distributions
      and can adopt different conformations which can affect the uptake of these
      molecules and influence the pathways of their toxic action.

PMID- 29028068
TI  - More than euglossines: the diverse pollinators and floral scents of Zygopetalinae
      orchids.
AB  - Floral volatile organic compounds (VOCs) play important roles in plant-pollinator
      interactions. We investigated the reproductive ecology and floral VOCs of
      Zygopetalinae orchids to understand the relationship between floral scents and
      pollinators. We performed focal observations, phenological censuses and breeding
      system experiments in eight species in southeast Brazil. Floral scents were
      collected and analysed using SPME/GC-MS. We performed multivariate analyses to
      group species according to affinities of their VOCs and define compounds
      associated to each plant. Dichaea cogniauxiana was pollinated by weevils which
      use their developing ovules, while D. pendula was pollinated by the same weevils
      and perfume-collecting male euglossine bees. The other species were deceit
      pollinated by bees. Zygopetalum crinitum was pollinated by carpenter bees, while
      W. warreana, Z. mackayi and Z. maxillare were bumblebee-pollinated. The latter
      was also pollinated by Centris confusa. Breeding system varied widely with no
      association to any pollinator group. Most VOCs are common to other floral scents.
      Zygopetalum crinitum presented an exclusive blend of VOCs, mainly composed of
      benzenoids. The scents of Pabstia jugosa, Promenaea xanthina and the Zygopetalum
      spp. were similar. The bumblebee-pollinated species have flowering periods
      partially overlapped, thus neither phenology nor pollinators constitute
      hybridization barriers among these species. Euglossines are not the only
      pollinators of Zygopetalinae. Different VOCs, size and lifespan of flowers are
      associated with distinct pollinators. A distinctive VOC bouquet may determine
      specialisation in carpenter bees or male euglossines within bee-pollinated
      flowers. Finally, visitation of deceit-pollinated flowers by perfume-collecting
      euglossines allows us to hypothesise how pollination by this group of bees had
      evolved.

PMID- 29028069
TI  - Acclimatization patterns in tropical reptiles: uncoupling temperature and
      energetics.
AB  - The physiological compensation of animals in changing environments through
      acclimatization has long been considered to be of minor importance in tropical
      ectotherms due to more stable climatic conditions compared to temperate regions.
      Contrasting this assumption are reports about a range of metabolic adjustments in
      tropical species, especially during the last two decades from field acclimatized
      animals. Metabolic rates are strongly linked to temperature in ectotherms but
      they also reflect energetic requirements and restrictions. We therefore postulate
      that the observed variety of acclimatization patterns in tropical reptiles
      results from an interaction of multiple influences, including food and water
      availability, rather than from thermal constraints alone. We present new data
      from two sympatric Malagasy lizards with contrasting acclimatization patterns
      and, complemented with an extensive literature search, discuss the variety of
      acclimatization patterns in tropical reptiles with regard to thermal and
      energetic influences. This broad consideration of constraints allows a
      rearrangement of apparently controversial patterns into a scheme of decreasing
      metabolic costs, including two new categories for selective and selective inverse
      acclimatization, where metabolic shifts are restricted to body temperatures below
      those preferred during activity.

PMID- 29028070
TI  - Gene expression in human adipose-derived stem cells: comparison of 2D films, 3D
      electrospun meshes or co-cultured scaffolds with two-way paracrine effects.
AB  - Finding the appropriate cues to trigger the desired differentiation is a
      challenge in tissue engineering when stem cells are involved. In this regard,
      three-dimensional environments are often compared to cells' two-dimensional
      culture behaviour (plastic culture dish). Here, we compared the gene expression
      pattern of human adipose-derived stem cells (ASC) seeded in a three-dimensional
      (3D) electrospun mesh and on a two-dimensional (2D) film - both of exactly the
      same material. Additionally, we conducted experiments with a scaffold floating
      above a film to investigate two-way paracrine effects (co-system). Electrospun
      meshes (3D scaffolds) and films (2D), consisting either of pristine poly-lactic
      co-glycolic acid (PLGA) or of PLGA-containing dispersed amorphous calcium
      phosphate nanoparticles (PLGA/aCaP), were seeded with ASCs and cultured either in
      Dulbecco Minimum Essential Medium (DMEM) or in osteogenic medium. After two
      weeks, minimum stem cell criteria markers as well as typical markers for
      osteogenesis, endothelial cell differentiation, adipogenesis and chondrogenesis
      were analysed by quantitative real-time PCR. Interestingly, mostly osteogenic
      genes of cells seeded on 3D meshes were upregulated compared to those on 2D
      films, while stem cell markers seemed to be only slightly affected. Runx2 and
      osteocalcin showed an especially strong upregulation under all conditions, while
      most other factors analysed for 2D/3D changes were highly dependent on the
      material composition, the culture medium and on paracrine signalling effects. The
      beneficial 3D environment for stem cells found in many studies has therefore not
      to be attributed to the third dimension alone and should carefully be compared to
      2D films fabricated of the same material. Furthermore, paracrine interactions
      triggering differentiation are not negligible.

PMID- 29028071
TI  - How to isolate a ready-to-use adipose-derived stem cells pellet for clinical
      application.
AB  - Adipose-derived stem cells (ASCs) are multipotent mesenchymal stem cells (MSCs)
      that show definitive stem cell characteristics such as plastic adherence in
      culture, ability to maintain multipotency upon in vitro expansion, and self
      renewal capacity. ASCs are particularly promising for use in regenerative
      medicine because they can be harvested easily from adipose tissue by standard
      liposuction, with minimal donor site morbidity. Since ASCs do not necessitate ex
      vivo expansion to obtain clinically significant cell numbers, it is critical to
      identify a standardized method that maximizes the number of ASCs collected. Based
      on current literature, there is no standardized method to isolate ASCs for
      clinical application. Furthermore, clinical studies involving ASCs often show
      inconsistencies in the reported results. Such studies often use research-derived
      isolation protocols, which are complex, time-consuming, and involve the use of
      chemical and animal-derived reagents. In this paper, we present an in-depth
      review of the available data on ASC isolation protocols. Moreover, we describe
      our isolation protocol that allows the collection of a ready-to-use ASC pellet
      for clinical application.

PMID- 29028072
TI  - Vitamin D in human reproduction: the more, the better? An evidence-based critical
      appraisal.
AB  - OBJECTIVE: Vitamin D is a fat-soluble secosteroid hormone that regulates calcium,
      magnesium, and phosphate homeostasis and plays a pivotal role as
      antiproliferative and immunomodulatory mediator. Considering the different
      sources of synthesis and dietary intake as well as the pleiotropic actions in
      extremely diverse (micro)environments of the body, the supplementation of this
      Vitamin should be carefully evaluated taking into account the several pathways
      that it regulates. In the current brief review, we aimed to summarize the
      available evidence about the topic, in order to suggest the best evidence-based
      supplementation strategy for human reproduction, avoiding the unuseful (and
      sometimes hazardous) empiric supplementation. MATERIALS AND METHODS: Narrative
      overview, synthesizing the findings of literature retrieved from searches of
      computerized databases. RESULTS: Accumulating evidence from in vitro
      fertilization (IVF) trials suggests that fertilization rate decreases
      significantly with increasing levels of 25OH-D in follicular fluid; in addition,
      Vitamin D levels in the follicular fluid are negatively correlated to the quality
      of embryos and the higher values of Vitamin D are associated with lower
      possibility to achieve pregnancy. Both low and high Vitamin D serum
      concentrations decrease not only spermatozoa count, but their progressive
      motility as well as increase morphological abnormalities. Finally, studies in
      animal models found that severe hypervitaminosis D can reduce the total skeletal
      calcium store in embryos and may compromise the postnatal survival. CONCLUSIONS:
      Based on the retrieved data, we solicit to be extremely selective in deciding for
      Vitamin D supplementation, since its excess may play a detrimental role in
      fertility.

PMID- 29028073
TI  - Polyphenol epigallocatechin-3-gallate alleviates high glucose-induced H9C2 cell
      damage through PI3K/Akt pathway.
AB  - OBJECTIVE: The aim of this work was to study the protective effect of polyphenol
      epigallocatechin-3-gallate (EGCG) on high glucose-induced oxidative damage of
      H9C2 cells and to investigate the relationship between this effect and
      phosphatidyl inositol 3 kinase-serine/threonine kinase (P13K/Akt) signal
      transduction pathway. MATERIALS AND METHODS: H9C2 cells were used as objects of
      study, 350 mM glucose serum-free medium was used as the high glucose molding
      condition, and LY294002 (10 MUM) was used as the PI3K/Akt inhibitor. 3-(4,5
      dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay was used to
      detect the cell viability, lactate dehydrogenase (LDH) assay was used to detect
      the cytotoxicity, flow cytometry was used to detect the proportion of cell
      apoptosis, and Western blotting was used to detect the expressions of cell
      associated proteins. RESULTS: Cell viability was reduced and cell apoptosis was
      increased by 350 mM high glucose. The high glucose-induced apoptosis was
      alleviated and the Akt expression in cells was increased by EGCG. The protective
      effect of EGCG was reduced after inhibition of PI3K/Akt pathway. CONCLUSIONS:
      EGCG protects H9C2 cells from high glucose-induced damage. EGCG plays the
      protective effect through inducing the PI3K/Akt pathway activation.

PMID- 29028074
TI  - Efficacy and safety of 5% lidocaine-medicated plasters in localized pain with
      neuropathic and/or inflammatory characteristics: an observational, real-world
      study.
AB  - OBJECTIVE: Based on clinical study results, 5% lidocaine-medicated plaster (5%
      LMP) is currently recommended for the treatment of localized peripheral
      neuropathic pain, such as post-herpetic neuralgia (PHN). However, its effective
      action, as well as the high safety, have indeed led to its use in clinical
      practice for pain conditions with similar pathophysiological mechanisms. In this
      study, the efficacy and safety of 5% LMP were investigated in patients with
      localized pain with neuropathic and/or inflammatory characteristics, such as PHN,
      post-traumatic/surgical or musculoskeletal pain. PATIENTS AND METHODS: 503
      patients with localized pain treated with 5% LMP were evaluated at baseline (T0),
      after 30 days (T30) and after 60 days (T60). The primary endpoint was number and
      proportion of 30% responders at T60, whereas secondary endpoints included number
      and proportion of 30% responders at T30, mean pain intensity, mean extension of
      the painful area, dynamic mechanical allodynia and quality of sleep. Evaluations
      were assessed in all patients and subgroups based on different clinical entities.
      Concomitant treatments and adverse reactions were also recorded. RESULTS: 72% and
      90% of all patients responded to 5% LMP treatment at T30 and T60, respectively.
      Comparable results were also obtained in subgroups such as PHN patients (72% and
      68% at T30 and T60, respectively), and musculoskeletal pain (73% and 83% at T30
      and T60, respectively). The mean pain intensity, as well as the extension of the
      painful area, significantly decreased during the study, in all patients and each
      subgroup. In addition, secondary endpoints significantly improved at each time
      point compared with baseline, in all groups. CONCLUSIONS: The effectiveness and
      safety of 5% LMP were shown in localized pain conditions such as neuropathic and,
      importantly, in musculoskeletal pain, a condition never investigated with this
      product. This field-practice study suggests that topical pain-reducing strategies
      such as 5% LMP could be effective in neuropathic and/or inflammatory, localized
      pain conditions.

PMID- 29028075
TI  - Safety of oral alpha-lipoic acid treatment in pregnant women: a retrospective
      observational study.
AB  - OBJECTIVE: Alpha-lipoic acid is a natural molecule, which directly or by means of
      its reduced form, dihydrolipoic acid, exerts antioxidant, anti-inflammatory and
      immunomodulatory activities, very helpful also in preventing miscarriage and
      preterm delivery. Used as dietary supplement alpha-lipoic acid was demonstrated
      to be safe for living organisms even when administered at high doses. However, no
      study was made so far to verify the safety of its continuous administration on a
      substantial number of pregnant women. The present investigation was performed to
      answer this issue. PATIENTS AND METHODS: An observational retrospective study was
      carried out analyzing 610 expectant mothers. They had been treated daily by oral
      route with 600 mg alpha-lipoic acid, for at least 7 weeks during gestation. The
      primary outcome was to verify alpha-lipoic acid safety in the mother and infant.
      Maternal safety was assessed by monitoring for adverse reactions, physical and
      clinical examination, including a morbidity assessment. Laboratory and clinical
      examinations were performed monthly. Neonatal safety was assessed by the
      evaluation of birth weight, gestational age, Apgar scores, neonatal death with
      the related cause of death. Data collected from the Birth Registry of Campania
      Region were used as control. RESULTS: This study provided a very clear and
      reassuring picture about the safety of alpha-lipoic acid oral treatment during
      pregnancy. No adverse effect was noticed in mothers or newborns. The two sets of
      monitored data, from treated and controls, were completely superimposable or, in
      some cases, better in alpha-lipoic acid group. CONCLUSIONS: Our results open a
      reassuring scenario regarding the administration of alpha-lipoic acid during
      pregnancy.

PMID- 29028076
TI  - Intestinal probiotics in relieving clinical symptoms of severe hand, foot, and
      mouth disease and potential mechanism analysis.
AB  - OBJECTIVE: In this prospective cohort study, the efficacy and action mechanism of
      an intestinal probiotic formulation, Golden Bifid, in severe hand, foot, and
      mouth disease (HFMD) were determined in 63 consecutively admitted patients
      successfully treated in the Pediatrics Emergency Department of our hospital.
      PATIENTS AND METHODS: All patients had a persistent fever; 43 patients had rashes
      on hands, feet, crissum, and hips; and 45 patients had neurological signs and
      symptoms. Patients were treated with standard supportive therapy along with
      ventilator-assisted respiration combined with bedside hemofiltration for removal
      of circulatory toxins and to achieve acid-base equilibrium and electrolyte
      stability. Golden Bifid was orally administered for 2 weeks, and vaccination was
      performed after patients were in stable condition. Additional supportive nursing
      care was also provided. Patients were categorized into the effective treatment (n
      = 40) and ineffective treatment (n = 23) groups. RESULTS: Serum levels of
      proinflammatory factors [interleukin (IL)-1beta, IL-6, tumor necrosis factor
      alpha, and interferon-gamma] were significantly decreased and those of anti
      inflammatory factors (IL-13, IL-4, and IL-10) were significantly increased after
      treatment in the effective treatment group. In contrast, in the ineffective
      treatment group, serum proinflammatory factor levels were significantly increased
      and serum anti-inflammatory factor levels were significantly decreased. Between
      group difference was significant. After treatment, serum D-lactic acid, diamine
      oxidase, and endotoxin levels were significantly decreased in the effective group
      and significantly increased in the ineffective group by intra- and inter-group
      comparisons. CONCLUSIONS: Intestinal probiotics were effective in relieving
      clinical symptoms of severe HFMD, maintaining intestinal immunity and anti
      inflammatory responses, and enhancing intestinal barrier function, with better
      safety and efficacy, which should be further evaluated for more extensive
      clinical applications.

PMID- 29028077
TI  - Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin
      as early biomarkers for predicting vancomycin-associated acute kidney injury: a
      prospective study.
AB  - OBJECTIVE: Previous studies have demonstrated that urinary kidney injury molecule
      1 (uKIM-1) and neutrophil gelatinase-associated lipocalin (uNGAL) were superior
      to serum creatinine (Scr) in detecting acute kidney injury (AKI), but their
      ability to predict clinical vancomycin-associated AKI has not been investigated.
      This study aimed to investigate the abilities of uKIM-1 and uNGAL individually
      and in combination to predict vancomycin-associated AKI. PATIENTS AND METHODS:
      Scr, uKIM-1, and uNGAL were measured on the day before and days 1, 2, and 3 of
      vancomycin therapy in a generalized adult population. Levels of these biomarkers
      between AKI and non-AKI groups were comparatively analyzed. Predictive
      performances were evaluated by receiver operating characteristic curve (ROC)
      analysis. RESULTS: A total of 87 patients were enrolled, and among them, 11
      (12.6%) patients developed AKI. Urinary KIM-1 and NGAL levels in the AKI group
      were higher than in the non-AKI group at all time points (p < 0.05), and the
      areas under the receiver operating characteristic curves (AUC) were 0.849 (95%
      confidence interval [CI] 0.750-0.948) for uKIM-1 and 0.824 (95% CI 0.726-0.922)
      for uNGAL, with cut-off values of 1.72 ng/mL and 9.07 ng/mL respectively. The AUC
      of uKIM-1 and uNGAL combined was 0.852 (95% CI 0.754-0.949), and the sensitivity
      and specificity were 90.9% and 75.0%, respectively. CONCLUSIONS: Urinary KIM-1
      and NGAL could efficiently discriminate patients with or without vancomycin
      associated AKI earlier than Scr, and the combined urinary biomarkers showed fair
      discrimination compared with the individual biomarkers.

PMID- 29028078
TI  - A natural pharma standard supplement formulation to control treatment-related
      toxicity and oxidative stress in genitourinary cancer: a preliminary study.
AB  - OBJECTIVE: Oncological treatments are associated with toxicities that may
      decrease compliance to treatment in most genitourinary cancer patients.
      Supplementation with pharmaceutical-standardized supplement may be a
      supplementary method to control the side effects after chemo- and radiotherapy
      and the increased oxidative stress associated to treatments. This registry study
      evaluated a natural combination of supplements containing curcumin, cordyceps,
      and astaxanthin (OncotrisTM) used as supplementary management in genitourinary
      cancer patients who had undergone oncological therapy. PATIENTS AND METHODS:
      Patients with genitourinary cancers (prostate or bladder malignancies) who had
      undergone and completed cancer treatments (radiotherapy, chemotherapy or
      intravesical immunotherapy with increased oxidative stress and residual symptoms)
      were recruited in this registry, supplement study. Registry subjects (n = 61)
      freely decided to follow either a standard management (SM) (control group = 35)
      or SM plus oral daily supplementation (supplement group = 26). Evaluation of
      severity of treatment-related residual side effects, blood count test, prostate
      specific antigen (PSA) test and plasma free radicals (oxidative stress) were
      performed at inclusion and at the end of the observational period (6 weeks).
      RESULTS: Two patients dropped out during the registry. Therefore, the analysis
      included 59 participants: 26 individuals in the supplementation group and 33 in
      the control group. In the supplement group, the intensity of signs and symptoms
      (treatment-related) and residual side effects significantly decreased at 6 weeks:
      minimal changes were observed in controls. Supplementation with OncotrisTM was
      associated with a significant improvement in blood cell count and with a
      decreased level of plasmatic PSA and oxidative stress. CONCLUSIONS: Naturally
      derived supplements, specifically OncotrisTM (patent pending), could support the
      body to overcome the treatment-related toxicities - and the relative oxidative
      stress in cancer patients.

PMID- 29028079
TI  - Potency on lowering serum uric acid in gout patients: a pooled analysis of
      registrative studies comparing febuxostat vs. allopurinol.
AB  - OBJECTIVE: Hyperuricemia leading to urate crystal formation in tissues represents
      the pathophysiological mechanism of gout. Guidelines recommend a therapeutic
      target of serum urate concentration (sUA) <6 mg/dL, or even lower (<=5 mg/dL) in
      patients with large deposits. We conducted an analysis with the aim to achieve
      additional insights into the urate-lowering efficacy of two xanthine oxidase
      inhibitors, allopurinol and febuxostat. PATIENTS AND METHODS: This was a pooled
      analysis of phase III trials on allopurinol and febuxostat, including 4101
      patients with gout and hyperuricemia. The efficacy outcomes were: mean reduction
      of sUA concentration from baseline; number of patients with target sUA levels
      (<6.0 mg/dL or <=5 mgdL); time to reach target sUA levels. RESULTS: Three
      registrative, phase III, randomized, multicenter, placebo-controlled/allopurinol
      controlled trials assessing the efficacy of febuxostat, were included. The mean
      reduction of sUA concentration with any dose of febuxostat was higher (-2.92+/
      2.87 mg/dL; -27%), with respect to placebo- (-0.62+/-1.84 mg/dL; -5%) and
      allopurinol-pooled groups (-2.41+/-2.20 mg/dL; -24%). Moreover, febuxostat showed
      a higher probability to achieve the recommended target sUA concentration than
      allopurinol [odds ratio: 2.43 (95% CI: 2.119-2.789) and 4.05 (95% CI: 3.41-4.82)
      for sUA levels <6 mg/dL and <=5 mg/dL, respectively]. Patients on any-dose
      febuxostat reached target sUA faster than allopurinol-treated patients (86.04+/
      71.47 vs. 98.76+/-70.88 days and 52.08+/-49.97 vs. 90.42+/-68.03 days for
      reaching sUA levels <6 mg/dL and <=5 mg/dL, respectively; p <0.001 for both
      comparisons). CONCLUSIONS: In patients with gout and hyperuricemia, febuxostat
      was significantly more effective and faster than allopurinol in obtaining the
      recommended target sUA levels, which were reached by a higher number of patients.
      Therefore, febuxostat was confirmed as an effective option for the treatment of
      hyperuricemia in gout.

PMID- 29028080
TI  - Roles of hypoxia-inducible factor-1alpha and its target genes in neonatal hypoxic
      pulmonary hypertension.
AB  - OBJECTIVE: To investigate the role of hypoxia-inducible factor-1alpha and its
      target genes in hypoxic pulmonary hypertension in neonates. PATIENTS AND METHODS:
      A total of 117 newborns were selected and divided into two groups for clinical
      experiments: 85 cases in the hypoxic pulmonary hypertension (HPH) group,
      including mild, moderate and severe subgroups, and 32 cases in the case-control
      group. ELISA was used to detect the serum HIF-1alpha, endothelin-1 (ET-1) and
      adrenomedullin (ADM) levels, and echocardiography was used to detect the dynamic
      changes in pulmonary artery systolic pressure (PASP), right ventricular ejection
      fraction (RVEF), tricuspid E peak and A peak ratio (E/A) and right ventricular
      Tei index. RESULTS: The average PASP level of the HPH group was significantly
      higher than that of the control group at 1 d and 3 d after birth (p < 0.05). The
      average PASP level was still higher in the severe HPH group than that in the
      control group at 7 d after birth, while the average levels in the mild and
      moderate HPH groups recovered to the normal. Compared with those in control
      group, RVEF and E/A of the tricuspid valve were decreased significantly in severe
      HPH patients (p < 0.05). The Tei indexes of the right ventricle were
      significantly higher in the mild, moderate and severe HPH groups than those in
      control group and the right ventricular Tei index was positively correlated with
      PASP. The levels of serum ADM, HHH-1alpha and ET-1 in all the three HPH subgroups
      were significantly higher than those in the control group at 1 d after birth and
      showed positive correlations with PASP (p < 0.05), except that serum ADM in mild
      HPH showed no obvious difference from the control group. The levels of serum HIF
      1alpha and ADM in the severe HPH group and the ET-1 levels in the moderate and
      severe groups were increased significantly at 3 d after birth (p < 0.05).
      CONCLUSIONS: The PASP level in neonates with HPH is related to the serum HIF
      1alpha, ET-1 and ADM levels, indicating that hypoxia can increase the level of
      HIF-1alpha, which in turn will enhance the expression of downstream target genes
      ET-1 and ADM, further leading to pulmonary hypertension. The right ventricular
      Tei index can be used to sensitively detect right ventricular dysfunction of
      mild, moderate and severe HPH groups.

PMID- 29028081
TI  - Serum YKL-40 level is correlated with apnea hypopnea index in patients with
      obstructive sleep apnea sindrome.
AB  - OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) has been associated with
      elevated biochemical markers of inflammation. Although the exact mechanism is
      unknown, both sleep deprivation and hypoxemia are believed to be important
      causative factors. YKL-40, also known as chitinase-like protein, has been shown
      to be related to various inflammatory conditions including atherosclerosis,
      diabetes, cancer, and asthma. The present study aimed to evaluate the
      relationship between YKL-40 levels and the Apnea Hypopnea Index (AHI) in patients
      with obstructive sleep apnea syndrome. PATIENTS AND METHODS: The study was
      conducted at the Sleep Unit of the Namik Kemal University Research Center. From
      January 2013 to December 2013, 120 patients diagnosed with OSAS by
      polysomnography and 40 subjects without OSAS were recruited. Patients in both
      groups were matched by age, sex, and body mass index (BMI). They were further
      divided into groups of mild, moderate and severe OSAS based on their AHI value.
      Serum YKL-40 concentrations were measured by the enzyme-linked immunosorbent
      assay (ELISA). RESULTS: OSAS patients showed significantly elevated YKL-40 levels
      compared to the control group; 102,05 (23.14) pg/ml in the control group vs.
      144.81 (65.53) pg/ml in the OSAS group. A Spearman correlation analysis showed
      that serum YKL-40 levels were significantly and positively correlated with AHI (r
      = 0.434, p < 0.001) and oxygen desaturation index (r = 0.374, p < 0.001).
      CONCLUSIONS: The study demonstrated that high serum YKL-40 levels correlated with
      the severity of OSAS and might serve as a nonspecific biomarker for prediction
      and progression of the disease.

PMID- 29028082
TI  - Evaluation of the role of 8-iso-PGF levels at multiple sites during intracranial
      hemorrhage in pediatric patients.
AB  - OBJECTIVE: The present study was planned to explore the role of 8-isomeric
      prostaglandinF2alpha (8-iso-PGF2alpha) levels at the multiple sites of
      cerebrospinal fluid in children with intracranial hemorrhage. PATIENTS AND
      METHODS: 90 children with intracranial hemorrhage were admitted to Surgery
      Intensive Care Unit (SICU) of our hospital from January to December 2013 and were
      selected as study subjects. They were divided into group A (n=30), group B (n=30)
      and group C (n=30). The group A was given conventional treatment, the group B was
      treated with minimally invasive puncture and the group C was treated with
      cerebrospinal fluid decompression. After 1 d, 2 d, 3 d, and 7 d of
      hospitalization, enzyme-linked immunosorbent assay (ELISA) was used to detect the
      8-iso-PGF2alpha levels in peripheral blood of children in all groups. On the day
      of admission and 10 d after treatment, 3 groups of children were implemented with
      brain nuclear magnetic resonance spectroscopy for metabolite analyses. RESULTS:
      On the day of admission there were no significant differences in the 8-iso
      PGF2alpha levels among group A, B and C. Further, after 1 d, 3 d, 7 d of hospital
      stay, the 8-iso-PGF2alpha levels in peripheral blood showed a gradual downward
      trend, and decline range of the group C was greater than that of group A and B (p
      < 0.05). After 10 days of treatment, there were significant differences in the
      bilateral temporal lobe and hippocampal NAA/Creatinine (Cr), Cho/Cr, mI/Cr and
      NAA/mI among group A, B, and C. The survival rate of group C was higher than that
      of group A and B (p < 0.05). On the other hand, the prevalence of sequelae was
      significantly lower than that of group A and B (p < 0.05). The amount of blood
      loss in children with intracranial hemorrhage was positively correlated with the
      levels of 8-iso-PGF2alpha in peripheral blood (r = 0.546, p < 0.05) as observed
      by Spearman correlation analysis. CONCLUSIONS: 8-iso-PGF2alpha plays an important
      role in the pathogenesis of intracranial hemorrhage, and could be utilized as a
      biomarker of oxidative stress in children with intracranial hemorrhage. Further,
      cerebrospinal fluid decompression is a better method of treatment for
      intracranial hemorrhage.

PMID- 29028083
TI  - Association between advanced oxidation protein products (AOPP) and vascular
      calcification in uremic patients.
AB  - OBJECTIVE: To investigate the correlation between serum advanced oxidation
      protein products (AOPP) and vascular calcification in uremic patients. PATIENTS
      AND METHODS: The general data of included subjects were collected, and the serum
      AOPP, intact parathyroid hormone (iPTH), creatinine (Cre), Urea, calcium (Ca),
      phosphorus (P), total cholesterol (TC), triglyceride (TG), low density
      lipoprotein cholesterin (LDL-C), hemoglobin (Hb) and albumin (ALB) were detected.
      Coronary artery computed tomography (CT) scan was performed and the coronary
      arterial calcification score (CACS) was calculated; the whole abdomen CT scan was
      performed and abdominal aortic calcification index (AACI) was calculated. SPSS
      l9.0 software was used for data analysis. RESULTS: The coronary artery CT and
      detection of serum indexes showed that AOPP in positive coronary arterial
      calcification group was significantly increased compared with that in negative
      coronary arterial calcification group (59.14 +/- 14.57 vs. 37.59 +/- 5.31)
      MUmol/L. The whole abdomen CT and detection of serum indexes showed that AOPP in
      positive abdominal aortic calcification group was significantly increased
      compared with that in negative abdominal aortic calcification group (60.32 +/-
      15.43 vs. 39.57 +/- 6.25) MUmol/L. AOPP in severe calcification group was
      significantly higher than negative group (70.72 +/- 18.18 vs. 39.57 +/- 6.25)
      MUmol/L. There were no significant differences in AOPP between hypertension and
      non-hypertension groups, diabetic nephropathy and non-diabetic nephropathy
      groups. Correlation analysis showed that AOPP of uremic patients had a
      significantly positive correlation with logl0[CACS+1] and had a significantly
      positive correlation with inferior AACI. CONCLUSIONS: AOPP in positive coronary
      arterial calcification group and positive abdominal aortic calcification group
      was higher than that in negative group and AOPP in severe calcification group was
      significantly higher than that in negative group. AOPP of uremic patients has a
      significantly positive correlation with CACS and AACI.

PMID- 29028084
TI  - Expression and clinical significance of aquaporin-1 and ET-1 in urine of children
      with congenital hydronephrosis.
AB  - OBJECTIVE: Congenital hydronephrosis is induced by congenital obstruction of
      uretero pelvic junction, bladder vesicoureteral reflux, posterior urethral valve,
      stricture of ureter end and ureterocyst, which is extremely apt to cause end
      stage renal failure in children. It becomes significant to explore the expression
      profile and clinical significance of aquaporin-1 (AQP-1) and ET-1 (endothelin-1)
      in the urine of children with congenital hydronephrosis. PATIENTS AND METHODS: 80
      cases of children with congenital hydronephrosis were selected to be the
      observation group and another 40 cases of children with other diseases were
      served as control group. Pre-operative morning urine, intra-operative renal
      pelvis urine and morning urine at the 7th day after the operation of all the
      children were collected for the detection of the level of ET-1, Cr level and AQP1
      in the urine. Urine various indexes of different diseases stages in children of
      both groups were compared. RESULTS: There was no significant difference between
      children with mild and children in control group (p > 0.05). In the observation
      group, the AQP-1 level during the operation was significantly lower than that
      before operation, but it was significantly higher in post-operation than that
      during the operation, which was still lower than that in control group (p <
      0.05). Urine ET-1 level in observation group and its positive rate were
      significantly higher than that in control group (p < 0.05). Serum stress indexes
      in each stage of the observation group were significantly higher than that in
      control group (p < 0.05). CONCLUSIONS: The expression levels of urine AQP-1 and
      ET-1 of children with congenital hydronephrosis were obviously increased. The AQP
      1 level during the operation was lower than that before operation. This post
      operation level was significantly higher than before the operation. The
      expression of AQP-1 and ET-1 could be used as important indexes for clinical
      diagnosis.

PMID- 29028085
TI  - Nestin and CD146 expression in metaplastic breast cancer: stem-cell therapy in
      need? Lessons reported from a male patient.
AB  - OBJECTIVE: Metaplastic breast carcinomas represent a rare subtype of breast
      cancer exhibiting aggressive clinical features. They appear as highly
      chemoresistant tumors, therefore showing poor outcome and high rates of local
      recurrence or distant metastasis. CASE REPORT: A 37-year-old greek man was
      referred to our hospital for evaluation of a locally advanced, ulcerated, fixed,
      irregular and hard in consistency mass covering his left breast and chest wall.
      Further work out with CT and biopsy of the tumor revealed a triple negative
      metaplastic breast cancer classified as cT4cN3cM1. The patient received first
      line chemotherapy and afterward a palliative resection of the tumor. The
      histology revealed the presence of a combined triple negative adenocarcinoma with
      a predominant metaplastic squamous carcinoma and a spindle cell (sarcomatoid)
      carcinoma of the breast. In the tissue sample stem cell markers, nestin and CD146
      (MCAM) were expressed, enhancing the theory that cancer cells of this tumor could
      possibly harbor stem cell properties. The patient received several chemotherapy
      regimens but died 6 months after the initiation of treatment. CONCLUSIONS:
      Metaplastic breast cancer consists of cells with stem cell properties. New
      targeted therapies are warranted in the view of the tumor's high resistance to
      conventional chemotherapy. Targeting nestin and CD146 might be a promising
      therapy as they seem to be implicated in the EMT pathway.

PMID- 29028086
TI  - Downregulation of microRNA-645 suppresses breast cancer cell metastasis via
      targeting DCDC2.
AB  - OBJECTIVE: To analyze the functioning mode of miR-645 on breast cancer cell
      metastasis and provide therapeutic targets for breast cancer. MATERIALS AND
      METHODS: Quantitative Real-time PCR (qRT-PCR) assay was employed to detect miR
      645 expression level. Wound healing assay and transwell assay were performed to
      investigate metastasis capacity of breast cancer cells. Protein levels were
      assessed by Western blotting assay. The target gene was predicted and verified by
      bioinformatics analysis and luciferase assay. RESULTS: MiR-645 was upregulated in
      breast cancer tissues when compared with pericarcinous tissues (n=60).
      Downregulated miR-645 could attenuate breast cancer cell migration and invasion
      capacities, as well as inhibit the process of epithelial-mesenchymal transition
      (EMT). DCDC2 was chosen as the target gene of miR-645 by bioinformatic analysis
      and Luciferase reporter assay. Moreover, the silence of DCDC2 could rescue tumor
      suppression role of downregulated miR-645 on breast cancer metastasis.
      CONCLUSIONS: Knockdown of miR-645 exerted tumor-suppressive effects on breast
      cancer metastasis via targeting DCDC2 in vitro, which provided an innovative and
      candidate target for diagnose and treatment of breast cancer.

PMID- 29028087
TI  - Axillary ectopic lobular carcinoma of breast: two rare case reports.
AB  - OBJECTIVE: The presence of ectopic or supernumerary breast tissue is a rare
      event, related to a not complete regression of breast tissue along the milk line.
      Primary ectopic breast cancer of the axilla can create many difficulties in
      differential diagnosis with subsequent delayed specific treatments. The incidence
      of ectopic breast tissue is 0.2-6%, and the axilla is the most common site
      involved. In this tissue, the same physiologic and pathologic changes as seen in
      ectopic breast tissue may occur, including carcinoma formation. PATIENTS AND
      METHODS: Two patients (a 56 years old and 70 years old women) came to our
      attention for the recent development painless nodular axillary lesions,
      clinically characterized by an increased thickness, irregular margins and
      adherence to the floors below. RESULTS: Patients underwent ultrasonography (US)
      and mammography (MMG) revealing non-specific features of the lesions. Magnetic
      resonance imaging (MRI), demonstrated margins slightly irregular and a non
      specific appearance of each lesion. Both patients underwent wide local excision
      with axillary lymph node dissection. Histological examination showed infiltrating
      lobular carcinomas of the breasts. CONCLUSIONS: We describe two unusual cases of
      ectopic axillary breast carcinoma localization. It is important a correct and
      fast diagnosis with a local examination, diagnostic instruments, surgical
      excision and histological examination.

PMID- 29028088
TI  - Antitumor effect of miR-27b-3p on lung cancer cells via targeting Fzd7.
AB  - OBJECTIVE:   Lung cancer is the most common malignancy with the highest mortality
      rate among cancers. microRNAs (miRNAs) have been confirmed to be closely related
      to the physiological disorder, especially the tumor process. This study aimed to
      investigate the effect of miR-27b-3p on lung tumor cells. MATERIALS AND METHODS:
      The expressions of miR-27b-3p in lung tumors and adjacent non-tumors lung tissues
      were compared. We test the bonding effect of miR-27b-3p on the Fzd7 promoter, and
      miR-27b-3p effects on the Fzd7 expression in both NCI-H446 and A549 cells. Then,
      effects of miR-27b-3p and Fzd7 on these cells viability, survival and apoptosis
      were detected, respectively. In addition, the possible mechanism of miR-27b-3p
      affected these cells apoptosis was explored by analyzing the expression of
      apoptosis-related factors. RESULTS: We found that miR-27b-3p was low expressed in
      lung tumors compared to adjacent non-tumorous lung tissues. miR-27b-3p directly
      targeted Fzd7 promoter and negatively regulated Fzd7 expression. Fzd7 promoted
      NCI-H446 and A549 cells viability and survival, inhibited cells apoptosis.
      However, miR-27b-3p effects on these cells were quite the opposite to Fzd7. The
      expressions of apoptosis-related factors were associated positively with miR-27b
      3p and showed a negative correlation with Fzd7 expression. CONCLUSIONS: The miR
      27b-3p was lowly expressed in lung cancer tissues, and played the role of a tumor
      suppressor. It could promote cell apoptosis and suppress cancer cells viability
      and survival via down-regulating Fzd7. It suggested that miR-27b-3p might be a
      potential target for the prophylaxis and treatment of lung cancer.

PMID- 29028089
TI  - The productions of atrial natriuretic peptide and arginine vasopressin in small
      cell lung cancer with brain metastases and their associations with hyponatremia.
AB  - OBJECTIVE: Hyponatremia is one of the most frequently encountered electrolyte
      disorder in small cell lung cancer (SCLC) patients. It was shown that some SCLC
      cell lines could produce atrial natriuretic peptide (ANP) and arginine
      vasopressin (AVP). The aim of the study was to assess the secretion of ANP, AVP
      and their relative contributions to hyponatremia in SCLC patients, especially in
      patients with brain metastases. PATIENTS AND METHODS: In total, 194 SCLC patients
      including 51 patients with brain metastases were collected. The levels of ANP and
      AVP were measured with radioimmunoassay kits. And then their associations with
      serum sodium were investigated. The progression-free survival (PFS) was compared
      between the hyponatremia group and the normal serum sodium group. RESULTS: Serum
      sodium was negatively correlated with the plasma levels of ANP (r=-0.171,
      p=0.017) and AVP (r = -0.244, p=0.001) in all SCLC patients. In the brain
      metastatic subgroup, there was also a negative correlation between serum sodium
      and ANP (r=-0.399, p=0.004), while there was no correlation between serum sodium
      and AVP (r=-0.232, p=0.101). The occurrence rate of hyponatremia (serum sodium
      values below 135 mmol/l) in patients with brain metastases (21/51, 41.18%) was
      higher than that in patients without brain metastases (37/143, 25.87%) (p=0.040).
      The progression-free survival (PFS) in the hyponatremia group was significantly
      shorter than that in patients of the group without hyponatremia (p=0.010).
      Moreover, compared with patients which regained normal serum sodium after the
      treatment, the PFS of patients still with hyponatremia after the treatment was
      significantly shorter (p=0.049). CONCLUSIONS: ANP might play a leading role in
      the formation of hyponatremia of SCLC patients with brain metastases. Correcting
      hyponatremia timely and appropriately could improve SCLC patients' prognosis.

PMID- 29028090
TI  - A comparative study on inflammatory factors and immune functions of lung cancer
      and pulmonary ground-glass attenuation.
AB  - OBJECTIVE: To compare the inflammatory factors and immune functions of patients
      with lung cancer and pulmonary ground-glass attenuation. PATIENTS AND METHODS: A
      total of 108 patients with pulmonary sarcoidosis treated in our hospital were
      selected and randomly divided into lung cancer group (Group A, n=32), diffuse
      ground-glass nodule group (Group B, n=35) and solitary ground-glass nodule group
      (Group C, n=41) according to the diagnosis results. Levels of inflammatory
      factors, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta),
      interleukin-6 (IL-6) and interleukin-10 (IL-10), in serum were detected via
      enzyme-linked immunosorbent assay (ELISA); the T-lymphocyte subset levels (CD3+,
      CD4+, CD8+ and CD4+/CD8+) in the immune system of patients in the three groups
      were detected using the flow cytometer; the levels of immunoglobulins,
      immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), were
      detected via immunoturbidimetric assay. RESULTS: There were no significant
      differences in the levels of TNF-alpha, IL-1beta, IL-6 and IL-10 in patients
      between Group A and Group B (p>0.05), but the levels in Group A and Group B were
      significantly higher than those in Group C (p<0.05). There were no significant
      differences in the levels of CD3+, CD4+, CD8+ and CD4+/CD8+ in patients between
      Group A and Group B (p>0.05), but the levels in Group A and Group B were
      significantly lower than those in Group C (p<0.05). There were no significant
      differences in the levels of IgG, IgA and IgM in patients between Group A and
      Group B (p>0.05), but the levels in Group A and Group B were significantly lower
      than those in Group C (p<0.05). CONCLUSIONS: There are lower inflammation and
      immune functions in patients with lung cancer and pulmonary ground-glass
      attenuation. Compared with those in patients with lung cancer and diffuse ground
      glass nodules, the inflammatory degree in patients with solitary ground-glass
      nodules is lower and the immune functions are better. Detecting the inflammatory
      factors and immune functions of patients can also be used as a differential
      diagnosis means of lung cancer.

PMID- 29028091
TI  - Investigation of serum miR-411 as a diagnosis and prognosis biomarker for non
      small cell lung cancer.
AB  - OBJECTIVE: Biomarkers in blood have become increasingly appreciated in the
      diagnosis and prognosis of non-small cell lung cancer (NSCLC). The purpose of the
      current study was to explore potential diagnostic and prognostic value of serum
      miR-411 in NSCLC patients. PATIENTS AND METHODS: 153 patients with NSCLC and 75
      healthy controls were enrolled in the study. Quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) was performed to determine the expression
      level of serum miR-411 in NSCLC patients and healthy controls. The association of
      miR-411 expression with clinicopathological factors or the prognosis of NSCLC
      patients was also analyzed. Patient survival was determined by telephone
      interview, and survival curves were plotted by using the Kaplan-Meier method and
      compared by the Log-rank test. Receiver operating characteristic curves was used
      to evaluate the sensitivity and specificity of serum miR-411. RESULTS: Our data
      showed that serum miR-411 levels were significantly greater in NSCLC patients
      than healthy controls (p < 0.001). High serum miR-411 expression was
      significantly associated with TNM stage (p = 0.018), lymph node status (p =
      0.006) and differentiated degree (p < 0.015). Kaplan-Meier analysis showed that
      high serum miR-411 expression levels predicted poor survival (p = 0.0053). The
      area under the curve (AUC) of high expression of serum miR-411 to diagnose NSCLC
      was 0.835 (95% CI: 0.737-0.933, p < 0.001). Univariate and multivariate analyses
      suggested that high expression of miR-411 was an independent poor prognostic
      indicator for NSCLC patients. CONCLUSIONS: The present results suggested that
      detection of serum miR-411 levels may have clinical potentials as a non-invasive
      diagnostic/prognostic biomarker for NSCLC patients.

PMID- 29028092
TI  - Long non-coding RNA ROR is a novel prognosis factor associated with non-small
      cell lung cancer progression.
AB  - OBJECTIVE: The aim of the present study was to determine the expression levels of
      long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) in
      non-small-cell lung cancer (NSCLC) patients and to further explore the prognostic
      value of this lncRNA. PATIENTS AND METHODS: In our investigation, we determined
      the expression of linc-ROR in human NSCLC tissues and matched normal lung tissues
      by quantitative Real-time-PCR analysis. Also, correlations between linc-ROR
      expression and the clinicopathological features were evaluated. Survival curves
      were plotted using the Kaplan-Meier method and differences in survival rates were
      analyzed using the log-rank test. Cox regression analyses were performed to
      explore the effect of linc-ROR as an independent predictor of survival. RESULTS:
      We found that linc-ROR had high expression in NSCLC specimens than that in
      matched adjacent normal lung tissues (p < 0.01). In addition, higher linc-ROR
      expression levels were positively correlated with advanced TNM stage (p = 0.007),
      positive distant metastasis (p = 0.001) and LN metastasis (p = 0.011).
      Furthermore, significantly shorter 5-year overall survival (OS) and disease-free
      survival (DFS) were observed in patients with higher expression of linc-ROR (both
      p < 0.001). In a multivariate Cox model, it was found that linc-ROR expression
      was an independent prognostic factor for both 5-years OS (p = 0.001) and 5-year
      DFS (p = 0.001) in NSCLC. CONCLUSIONS: Our findings indicate that linc-ROR plays
      an oncogenic role in NSCLC development and may function as a prognostic and
      predictive biomarker for NSCLC.

PMID- 29028094
TI  - Upregulation of miR-802 suppresses gastric cancer oncogenicity via targeting
      RAB23 expression.
AB  - OBJECTIVE: The aberrant expression of microRNAs (miRNAs) has been observed in
      various types of cancer. Recently, miR-802 was found to play important role in
      tumor progression. However, the function of miR-802 in gastric cancer (GC)
      remains unknown. The aim of the present study was to investigate biological
      effects and underlying mechanisms of miR-802 in GC. PATIENTS AND METHODS:
      Quantitative RT-PCR was performed to evaluate the expression level of miR-802 in
      GC tissues and cell lines. The in vitro cell proliferation was measured using the
      MTT method. Cell invasion and migration assays were performed using the transwell
      assay. The effects of miR-802 on tumor growth were examined using a GC xenograft
      model. Flow cytometry method was used to detect the effect of miR-802 in
      apoptosis of GC cells. Targets of miR-802 were predicted using bioinformatics and
      validated using luciferase reporter and Western blot analyses. RESULTS: The
      results showed that miR-802 was significantly down-regulated in GC tissues and
      cell lines. The enforced expression of miR-802 induced growth suppression and
      apoptosis of GC cells. Moreover, miR-802 overexpression suppressed the migration
      and invasion of GC cells. Bioinformatics analysis predicted that the RAB23 was a
      potential target gene of miR-802. The results of luciferase reporter assay
      demonstrated that miR-802 could directly target RAB23. Additionally, in vivo
      analysis, the xenograft mouse model also confirmed the suppressive effects of miR
      802 on tumor growth. CONCLUSIONS: Our results are the first to demonstrate the
      tumor-suppressive role of miR-802 in GC. The identification of miR-802 and its
      novel target RAB23 will be valuable in developing therapeutic applications for
      GC.

PMID- 29028093
TI  - miR-144-3p serves as a tumor suppressor by targeting FZD7 and predicts the
      prognosis of human glioblastoma.
AB  - OBJECTIVE: Previous research indicated that miR-144-3p was associated with the
      regulation of the carcinogenic processes, but the role of miR-144-3p in
      glioblastoma (GBM) remains unclear. In this study, we aimed to analyze the role
      of miR-144-3p in GBM. PATIENTS AND METHODS: The expression of miR-144-3p was
      measured in GBM tissues and adjacent non-malignant tissues using qRT-PCR. The
      correlation of miR-144-3p with clinicopathological features and prognosis was
      also analyzed. Cell proliferation, invasion, and migration assay were applied to
      assess the function of miR-144-3p in vitro. Bioinformatics prediction and
      luciferase assays were employed to identify the predicted microRNA (miRNA) which
      regulates Frizzled-7 (FZD7). The levels of FZD7 and FZD7 mRNA were determined by
      Western blot and RT-PCR. RESULTS: The results showed that the miR-144-3p
      expression was significantly downregulated in tumor tissues and GBM cell lines
      compared with that in normal brain tissues and the normal human astrocytes. The
      levels of miR-144-3p were negatively correlated with the status of WHO grade and
      recurrence. Furthermore, patients with low serum levels of miR-144-3p had a
      significantly shorter median overall survival rate. Multivariate Cox regression
      analysis confirmed that low level of miR-144-3p expression predicted poor
      prognosis independently. Further function assays showed that miR-144-3p inhibited
      proliferation invasion and migration of GBM cells. Finally, miR-144-3p was
      demonstrated to bind to the wild-type 3' untranslated region of FZD7 but not with
      its mutant. CONCLUSIONS: The results of the present study indicate that miR-144
      3p suppresses tumor metastasis by targeting FZD7. This work also provides strong
      evidence that miR-144-3p is an independent prognostic factor for patients with
      GBM.

PMID- 29028095
TI  - BCAR4 increase cisplatin resistance and predicted poor survival in gastric cancer
      patients.
AB  - OBJECTIVE: Gastric cancer is a common malignancy with increasing worldwide
      incidence, and chemotherapeutic drugs for gastric cancer are not effective. Long
      non-coding RNA (lncRNA) has been proved to be important in different cancer
      progression. In this research, we investigated whether lncRNAs have relations
      with drug resistance in gastric cancer to find new potential targets for therapy,
      which can increase the survival time of the drug-resistant gastric patient.
      PATIENTS AND METHODS: qRT-PCR was used to detect the expression of BCAR4 in 113
      cases of gastric cancer tissue and adjacent tissue, and the clinical significance
      was also analyzed. MTT assays and Western blot were performed to cytologically
      determine the relationship between BCAR4 expression and cisplatin resistance, as
      well as to investigate the potential molecular mechanism involved. RESULTS:
      Compared with the adjacent tissues, we found that BCAR4 was highly expressed in
      gastric cancer tissues. We also found that the expression of BCAR4 was
      significantly related to the size of the tumor, clinical classification and the
      survival time. In cytological experiments, we found the expression of BCAR4 was
      enhanced in cisplatin-resistant cell strains (SGC7901/DDP). What's more,
      overexpression of BCAR4 in SGC7901 cells increased resistance to cisplatin while
      reduced BCAR4 expression increased the sensitivity of SGC7901/DDP cells to
      cisplatin. Western blot experiments indicated that elevated expression of BCAR4
      upregulated tumor stem cell-related biomarkers via regulating Wnt signaling
      pathway. CONCLUSIONS: We showed that BCAR4 was closely related with the cisplatin
      resistant gastric cancer. It might be a promising target for treating gastric
      cancer and improving the efficiency of chemotherapeutic drugs.

PMID- 29028096
TI  - Expressions of HIF-1alpha and KISS-1 in patients with liver cancer and
      correlation analysis.
AB  - OBJECTIVE: To study the expressions of hypoxia-inducible factor-1alpha (HIF
      1alpha) and tumor metastasis suppressor gene (KISS-1) in patients with liver
      cancer and to analyze the correlation between HIF-1alpha and KISS-1 and liver
      cancer. PATIENTS AND METHODS: 20 normal liver tissues and 30 liver cancer tissues
      in our hospital were selected. The expressions of HIF-1alpha and KISS-1 in normal
      liver tissues and liver cancer tissues were detected via immunofluorescence
      assay. The mRNA expressions of HIF-1alpha and KISS-1 in normal liver tissues and
      liver cancer tissues were detected via reverse transcription polymerase chain
      reaction (RT-PCR). The protein expressions of HIF-1alpha and KISS-1 in normal
      liver tissues and liver cancer tissues were detected via Western blotting.
      Differences of HIF-1alpha and KISS-1 expressions in normal liver tissues and
      liver cancer tissues were analyzed using SPSS 17.0 statistical software. RESULTS:
      Immunofluorescence assay, RT-PCR, and Western blotting, showed that HIF-1alpha
      was highly expressed in liver cancer tissues, and its expression level was
      significantly higher than that in normal liver tissues. However, the expression
      of KISS-1 in normal liver tissues was significantly higher than that in liver
      cancer tissues. The results of analysis of variance showed that the differences
      of HIF-1alpha and KISS-1 expressions in normal liver tissues and liver cancer
      tissues were statistically significant (p<0.01). CONCLUSIONS: The abnormal
      expressions of HIF-1alpha and KISS-1 are closely related to the development and
      progression of liver cancer, indicating that HIF-1alpha and KISS-1 have important
      research values in liver cancer, and the expressions of HIF-1alpha and KISS-1 can
      be used as the index of deterioration degree of liver cancer, providing a new
      clinical basis for diagnosis and treatment.

PMID- 29028097
TI  - MicroRNA-217 functions as a prognosis predictor and inhibits pancreatic cancer
      cell proliferation and invasion via targeting E2F3.
AB  - OBJECTIVE: Pancreatic cancer (PC) is the most malignant tumor among all the
      tumors in the digestive system. MiR-217 has been reported to take a critical part
      in various malignant tumors. The aim of this study was to explore the function of
      MiR-217 in pancreatic cancer and its target genes. PATIENTS AND METHODS: Twenty
      pairs of PC tissues and matched normal adjacent pancreatic tissues were
      collected. The expression of miR-217 in PC tissues and normal pancreatic tissues
      was detected by Real-time polymerase chain reaction (PCR). PC cells were
      transfected with miR-217 mimics, inhibitors and negative control, respectively.
      Cell Counting Kit-8 (CCK-8) assay was used to detect cell viability. Cell
      apoptosis was checked via Annexin V-FITC/PI apoptosis kit. The protein expression
      of E2F3 was detected by Western blot. To detect repression by miR-217, HEK293T
      cells were co-transfected with the indicated E2F3 3'-UTR luciferase reporter.
      RESULTS: The expression of miR-217 was reduced in PC tissues comparing to normal
      pancreatic tissues. Meantime, the in-vitro study revealed that miR-217 suppressed
      PC cell growth, invasion but promoted apoptosis. Next, we proved that E2F3 was
      the target of miR-217 on PC cell function. CONCLUSIONS: miR-217 suppresses PC
      cell growth, invasion but promotes apoptosis in vitro through targeting E2F3. The
      miR-217-E2F3 axis may be used for PC therapy.

PMID- 29028098
TI  - Down-regulation of miR-329-3p is associated with worse prognosis in patients with
      cervical cancer.
AB  - OBJECTIVE: miR-329-3p has been reported to serve as a tumor suppressor in the
      progression of cervical cancer (CC). The aim of this study was to investigate the
      clinical significance of miR-329-3p in human CC. PATIENTS AND METHODS:
      Quantitative RT-PCR (qRT-PCR) was used to detect miR-329-3p expression in CC
      tissue samples and matched normal cervical tissues. The x2 test was used to
      analyze the association between miR-329-3p expression and clinical features of CC
      patients. Moreover, we evaluated the prognostic value of miR-329-3p by Kaplan
      Meier survival curve and Cox regression model. RESULTS: We found that the mean
      expression level of miR-329-3p in CC tissues was significantly lower than the
      mean level in the adjacent normal tissues samples (p < 0.01). MiR-329-3p level
      was significantly associated with lymph node metastasis (p = 0.013), FIGO stage
      (p = 0.024) and distant metastasis (p = 0.001). Furthermore, a significant
      difference was found, that CC patients with low miR-329-3p expression level had
      distinctly shorter overall survival than patients with high miR-329-3p expression
      level (p = 0.001). Finally, multivariate analyses indicated that miR-329-3p
      represented an independent predictor for overall survival of CC (p = 0.04).
      CONCLUSIONS: These results indicated, for the first time, that down-regulation of
      miR-329-3p was associated with poor prognosis in CC patients. MiR-329-3p can be
      used as an independent factor to predict survival of patients with CC.

PMID- 29028099
TI  - The diagnostic value of determination of serum GOLPH3 associated with CA125,
      CA19.9 in patients with ovarian cancer.
AB  - OBJECTIVE: To evaluate the value of three tumor markers serum Golgi
      phosphoprotein-3 (GOLPH3), cancer antigen 125 (CA125) and cancer antigen 19-9
      (CA19.9) in the diagnosis and postoperative evaluation of ovarian cancer by
      detecting these three markers. PATIENTS AND METHODS: A total of 187 patients were
      studied and included in the ovarian cancer group, benign pelvic mass group, and
      the normal control group. The levels of serum Golgi phosphoprotein-3 (GOLPH3),
      cancer antigen 125 (CA125) and cancer antigen 199 (CA19.9) were detected,
      respectively, and their effects on the diagnosis, evaluation, pathology typing
      and staging of ovarian cancer were measured. RESULTS: The sensitivity of the
      detection of ovarian cancer by GOLPH3 combined with CA125 and CA19.9 was higher
      than that by a single marker (p<0.05). The level of serum GOLPH3 in patients with
      serous and endometrioid carcinoma was significantly higher than that in patients
      with mucinous carcinoma, clear-cell carcinoma and germ cell tumor (p<0.05). There
      was no significant statistical difference in serum GOLPH3 level between patients
      with ovarian malignancies at stage III-IV and those at stage I-II (p>0.05). The
      levels of serum GOLPH3, CA125 and CA19.9 in patients with ovarian malignancies
      after surgery were significantly lower than those before surgery (p<0.05).
      CONCLUSIONS: The combined detection by GOLPH3, CA125, and CA19.9 may improve the
      diagnosis rate of ovarian epithelial cancer. GOLPH3, as a new ovarian cancer
      tumor marker used in clinical diagnosis, is expected to become an important
      indicator for the early diagnosis of ovarian cancer and the determination of
      clinical surgery efficacy.

PMID- 29028100
TI  - ZEB1 promotes prostate cancer proliferation and invasion through ERK1/2 signaling
      pathway.
AB  - OBJECTIVE: Prostate cancer is a kind of malignancy with high occurrence in the
      male urogenital system. However, the mechanism of the occurrence, the
      progression, and the metastasis of prostate cancer are still unclear. Searching
      for the effective molecule target is of great significance to improve the
      curative effect on prostate cancer. Zinc finger E box binding protein-1 (ZEB1)
      protein is a member of the zinc finger transcription factor family that
      participates in the embryonic development and formation. ZEB1 was found to be
      involved in the occurrence and in the development of multiple cancers, while its
      role in prostate cancer still needs elucidation. MATERIALS AND METHODS: Normal
      prostate cell line PC-3M and prostate cancer cell line DU145 were cultured in
      vitro and transfected by ZEB1 siRNA. ZEB1 mRNA and protein expressions were
      detected by real-time PCR and Western blot assay. Cell proliferation was
      determined by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium
      bromide (MTT) assay. Cell migration was evaluated by transwell assay. Cell
      apoptosis was evaluated by caspase-3 activity. The impact of ZEB1 on
      extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathway was
      assessed by Western blot assay. RESULTS: ZEB1 expression significantly increased
      in DU145 cells compared with PC-3M cells (p<0.05). ZEB1 mRNA and protein
      obviously declined, cell proliferation inhibited, cell invasion suppressed, and
      Caspase-3 activity enhanced in DU145 cells after ZEB1 siRNA transfection
      (p<0.05). ZEB1 siRNA markedly decreased ERK1/2 phosphorylation in DU145 cells
      compared with control (p<0.05). CONCLUSIONS: Inhibition of ZEB1 promoted prostate
      cancer apoptosis, restrained proliferation, and suppressed invasion through down
      regulating ERK1/2 signaling pathway.

PMID- 29028101
TI  - TopBP1 promotes malignant progression and correlates with poor prognosis in
      osteosarcoma.
AB  - OBJECTIVE: Topoisomerase IIbeta binding protein 1 (TopBP1) is involved in DNA
      damage and replication checkpoint and has been shown to be related to
      tumorigenesis in many cancer types. This study aimed to evaluate the biological
      role and clinicopathological significance of TopBP1 in OS. PATIENTS AND METHODS:
      TopBP1 expression in sarcoma patients was determined through the Oncomine
      database, and the prognostic role of TopBP1 expression was assessed in a
      retrospective cohort study. CCK-8 assay and colony formation assay were employed
      to evaluate the effect of TopBP1 on proliferation and chemoresistance in OS
      cells. Cell apoptosis and cell cycle assay were used to assess the effect of
      TopBP1 on apoptosis and cycle of OS cells. RESULTS: We observed that TopBP1
      expression was elevated not only in OS, but also in other sarcoma types including
      myxofibrosarcoma, liposarcoma, and leiomyosarcoma. Knockdown of TopBP1 using
      small interfering (si) RNA blocked cell proliferation and colony formation
      ability, and caused cell apoptosis as well as G1-phase arrest in OS cells.
      Moreover, TopBP1 knockdown decreased the chemoresistance of OS cells to both
      doxorubicin and cisplatin. Lastly, the retrospective cohort study showed that
      high TopBP1 expression was not only associated with high local recurrence and low
      necrosis rate, but also correlated with poor overall survival and disease-free
      survival of OS patients. CONCLUSIONS: Our findings indicate that TopBP1
      contributes to the cell survival and chemoresistance to doxorubicin and cisplatin
      of OS, suggesting TopBP1 may serve as a novel target for inhibition of
      progression and chemotherapeutic resistance in OS patients.

PMID- 29028102
TI  - The ten commandments of hepatic radioembolization: expert discussion and report
      from Mediterranean Interventional Oncology (MIOLive) congress 2017.
AB  - Microsphere and particle technology represent the next-generation agents that
      have formed the basis of interventional oncology, an evolving subspecialty of
      interventional radiology. One of these platforms, yttrium-90 microspheres, is
      increasingly being used as a treatment modality for primary and secondary liver
      tumors. Due to the widespread use of radioembolization, a comprehensive review of
      the methodologic and technical considerations seems to be mandatory. This article
      summarizes the expert discussion and report from Mediterranean Interventional
      Oncology Live Congress (MIOLive 2017) that was held in Rome, Italy, integrating
      evidence-reported literature and experience-based perceptions, to assist not only
      residents and fellows who are training in interventional radiologists but also
      practicing colleagues who are approaching to this intra-arterial treatment.

PMID- 29028103
TI  - Expressions of IL-1alpha and MMP-9 in degenerated lumbar disc tissues and their
      clinical significance.
AB  - OBJECTIVE: To observe the expression levels of interleukin-1alpha (IL-1alpha) and
      matrix metalloproteinase-9 (MMP-9) in degenerated lumbar disc tissues and to
      investigate their clinical significance. PATIENTS AND METHODS: Fifty patients
      with lumbar disc degeneration received the operative treatment were divided into
      three groups according to the magnetic resonance imaging (MRI) results:
      protrusion group, extrusion group, and free group. The degenerated intervertebral
      disc tissues were taken, and the normal intervertebral disc tissues of 20
      patients received the operative treatment due to lumbar bursting fracture, and
      were selected as the control group. The bone mineral densities of all patients
      were measured. The mRNA and protein expression levels of MMP-9 and IL-1alpha were
      detected via Real-time polymerase chain reaction (PCR) and enzyme-linked
      immunosorbent assay (ELISA), respectively. RESULTS: The bone mass of patients
      with lumbar disc degeneration was significantly decreased compared with that of
      the control group, and the bone mass was decreased more significantly in a free
      group than that in protrusion group. The mRNA and protein levels in IL-1alpha and
      MMP-9 of patients with lumbar disc degeneration were significantly increased
      compared with those in control group; the mRNA and protein levels in IL-1alpha
      and MMP-9 of extrusion group and free group were significantly higher than those
      in protrusion group, and the mRNA and protein levels in IL-1alpha and MMP-9 of
      free group were significantly higher than those in extrusion group. CONCLUSIONS:
      The levels of IL-1alpha and MMP-9 in degenerated lumbar disc tissues are higher
      than normal levels, and the increasing levels are positively correlated with the
      disease condition.

PMID- 29028104
TI  - The influence of ovulation induction and assisted conception on maternal and
      perinatal outcomes of twin pregnancies.
AB  - OBJECTIVE: To compare obstetrical and neonatal outcomes of twin pregnancies
      conceived via assisted reproductive technology (ART) with those of naturally
      conceived ones and to investigate the influence of the ART procedure type on
      these parameters. PATIENTS AND METHODS: This observational study included 450 ART
      and 647 spontaneous twin pregnancies delivered over 15 years at a single
      university-based hospital of Rome, Italy. Logistic and linear regression models
      adjusted for confounding factors were used to evaluate the effect of ART and the
      type of assisted conception (IVF/ICSI, ovulation induction +/- intrauterine
      insemination, egg/embryo donation) on maternal and perinatal outcomes. RESULTS:
      The mean gestational age was significantly lower in pregnancies conceived via
      ART. The occurrence rates of gestational diabetes, antenatal admission,
      prophylactic administration of corticosteroid, very preterm delivery and neonatal
      intensive care unit admission were higher in the ART group. Twin pregnancies
      achieved via egg/embryo donation had a lower risk of maternal thrombocytopenia
      and cervical incompetence and were at greater risk of receiving corticosteroid
      prophylaxis and patent ductus arteriosus than pregnancies obtained by IVF/ICSI.
      Conception by ovulation induction was associated with reduced risk of hyperemesis
      gravidarum and longer neonatal hospitalization compared to pregnancies obtained
      by IVF/ICSI. CONCLUSIONS: Assisted conception was associated with adverse
      obstetrical outcomes and lower gestational age, but after adjustment for
      gestational age neonatal immediate outcomes were similar to those observed in the
      spontaneous group. There were no many important differences in the outcomes of
      twin pregnancies obtained by a different type of conception.

PMID- 29028105
TI  - Value of confocal laser endomicroscopy in the diagnosis of vocal cord lesions.
AB  - OBJECTIVE: The aim of this study was to assess the reliability and limitations of
      confocal laser endomicroscopy (CLE) for diagnosing lesions of the vocal cords and
      differentiating malignant from non-malignant lesions. PATIENTS AND METHODS:
      During microlaryngoscopy, the vocal cords were scanned by probe-based CLE (pCLE:
      a GastroFlex probe with the Cellvizio(r) laser system, Mauna Technologies, Paris,
      France). The video recordings were analyzed and compared with the histological
      results. Thirty-one representative images were extracted and presented to four
      medical professionals (blinded examiners) for assessment. RESULTS: The accuracy
      for the category malignant/nonmalignant ranged between 58.1% and 87.1%. Overall
      interrater reliability was 0.29. Sensitivity ranged between 45.5 and 100%,
      specificity between 60.0 and 100%, PPV between 38.5% and 100% and NPV between
      66.7 and 100%. CONCLUSIONS: CLE is a promising method for the non-invasive
      diagnosis of vocal cord lesions in vivo, but factors such as small penetration
      depth, not available contrast media for the nuclei and subjective analyses of the
      images limit, at the moment, its diagnostic value.

PMID- 29028106
TI  - Correlation between presence of primary iris- and cilliary body cysts and
      intraocular pressure.
AB  - OBJECTIVE: The objective of this study was to examine the correlation between the
      presence of primary iris-ciliary cysts and the intraocular pressure. PATIENTS AND
      METHODS: Sixty patients with short-sightedness undergoing routine examination for
      laser vision correction in our hospital in 2003 were enrolled. Patients with
      known high intraocular pressure and risk of glaucoma were excluded from the
      study. A total of 119 eyes were examined by the Ultrasound Biomicroscope (UBM),
      and the presence of the primary iris-ciliary cysts was confirmed. Intraocular
      pressure was measured by using a blowing tonometer for each eye in triplicate.
      Through Pentacam correction of intraocular pressure using the Ehlers formula, the
      influence of the thickness of central cornea on intraocular pressure was
      excluded. RESULTS: Among all participants, 62 eyes (52.1%) were with high myopia,
      57 eyes (47.9%) with low and moderate myopia, 27 eyes (22.7%) with single cyst,
      20 eyes (16.8%) with multiple cysts, and 72 eyes (60.5%) were free from cysts.
      Moreover, the intraocular pressure was found within the normal range in 72 eyes
      (60.5%), and abnormally high in 47 eyes (39.5%). CONCLUSIONS: Our results showed
      that the presence of primary iris-ciliary cysts and the intraocular pressure were
      positively correlated, with a correlation coefficient of 0.235 (p = 0.01). These
      findings may prove useful for prediction and screening of high intraocular
      pressure.

PMID- 29028107
TI  - Platelet-rich plasma and myocardial regeneration.

PMID- 29028108
TI  - Effect of VEGF on neuronal degeneration and interaction between Alzheimer's
      disease biomarkers.
AB  - The article "Effect of VEGF on neuronal degeneration and interaction between
      Alzheimer's disease biomarkers" by H.-C. Yuan, C.-W. Jiang, L.-Y. Hou, Y.-B. Lv,
      X.-Z. Feng, L.-F. Guo, G. Sun, K. Liu, Y.-J. Liu, B. Xu, C.-Y. Wang, published in
      Eur Rev Med Pharmacol Sci 2017; 21 (16): 3649-3657 has been withdrawn.

PMID- 29028109
TI  - Research on the correlation of urine calcium integrin binding protein-1 and pro
      BNP with ischemic heart failure.
AB  - OBJECTIVE: To investigate the correlation between the levels of urine calcium
      integrin binding protein-1 (CIB1) and serum precursor N-terminal brain
      natriuretic peptide (pro-BNP) and ischemic heart failure. PATIENTS AND METHODS:
      30 patients diagnosed as acute ischemic heart failure for the first time in our
      hospital from January to August 2016 were continuously selected as the
      observation group 1, 30 patients with chronic stable ischemic heart failure as
      the observation group 2, and 30 healthy volunteers as the control group. Urine
      CIB1 level was detected via enzyme linked immunosorbent assay (ELISA) and serum
      pro-BNP level was detected via radioimmunoassay. The linear correlation between
      the CIB1 and pro-BNP levels in observation group 1 was observed, and the
      diagnostic value of CIB1 and pro-BNP levels for chronic stable ischemic heart
      failure were analyzed using the receiver operating characteristic (ROC) curve.
      RESULTS: CIB1 and pro-BNP levels in the observation group 1 were significantly
      higher than those in the observation group 2. These levels were significantly
      lower in the control group (p < 0.05). In the observation group 1, CIB1 and pro
      BNP levels were positively correlated (p < 0.05). The diagnostic accuracy of CIB1
      for chronic stable ischemic heart failure in the observation group 2 (area under
      the curve, AUC) was 0.854, the sensitivity was 86.6% and the specificity was
      82.5%, respectively. The diagnostic accuracy of pro-BNP was 0.823, the
      sensitivity was 83.5% and the specificity was 85.9%, respectively. CONCLUSIONS:
      There is a significant correlation between the urine CIB1 and serum pro-BNP
      levels in patients with acute ischemic heart failure. In patients with chronic
      stable ischemic heart failure, the diagnostic value of urine CIB1 outperforms
      that of serum pro-BNP, which still needs further study.

PMID- 29028111
TI  - DNA methylation of methylation complex genes in relation to stress and genome
      wide methylation in mother-newborn dyads.
AB  - OBJECTIVES: Early life stress is known to have enduring biological effects,
      particularly with respect to health. Epigenetic modifications, such as DNA
      methylation, are a possible mechanism to mediate the biological effect of stress.
      We previously found correlations between maternal stress, newborn birthweight,
      and genome-wide measures of DNA methylation. Here we investigate ten genes
      related to the methylation/demethylation complex in order to better understand
      the impact of stress on health. MATERIALS AND METHODS: DNA methylation and
      genetic variants at methylation/demethylation genes were assayed. Mean
      methylation measures were constructed for each gene and tested, in addition to
      genetic variants, for association with maternal stress measures based on
      interview and survey data (chronic stress and war trauma), maternal venous, and
      newborn cord genome-wide mean methylation (GMM), and birthweight. RESULTS: After
      cell type correction, we found multiple pairwise associations between war trauma,
      maternal GMM, maternal methylation at DNMT1, DNMT3A, TET3, and MBD2, and
      birthweight. CONCLUSIONS: The association of maternal GMM and maternal
      methylation at DNMT1, DNMT3A, TET3, and MBD2 is consistent with the role of these
      genes in establishing, maintaining and altering genome-wide methylation patterns,
      in some cases in response to stress. DNMT1 produces one of the primary enzymes
      that reproduces methylation patterns during DNA replication. DNMT3A and TET3 have
      been implicated in genome-wide hypomethylation in response to glucocorticoid
      hormones. Although we cannot determine the directionality of the genic and genome
      wide changes in methylation, our results suggest that altered methylation of
      specific methylation genes may be part of the molecular mechanism underlying the
      human biological response to stress.

PMID- 29028110
TI  - Melanoma staging: Evidence-based changes in the American Joint Committee on
      Cancer eighth edition cancer staging manual.
AB  - Answer questions and earn CME/CNE To update the melanoma staging system of the
      American Joint Committee on Cancer (AJCC) a large database was assembled
      comprising >46,000 patients from 10 centers worldwide with stages I, II, and III
      melanoma diagnosed since 1998. Based on analyses of this new database, the
      existing seventh edition AJCC stage IV database, and contemporary clinical trial
      data, the AJCC Melanoma Expert Panel introduced several important changes to the
      Tumor, Nodes, Metastasis (TNM) classification and stage grouping criteria. Key
      changes in the eighth edition AJCC Cancer Staging Manual include: 1) tumor
      thickness measurements to be recorded to the nearest 0.1 mm, not 0.01 mm; 2)
      definitions of T1a and T1b are revised (T1a, <0.8 mm without ulceration; T1b, 0.8
      1.0 mm with or without ulceration or <0.8 mm with ulceration), with mitotic rate
      no longer a T category criterion; 3) pathological (but not clinical) stage IA is
      revised to include T1b N0 M0 (formerly pathologic stage IB); 4) the N category
      descriptors "microscopic" and "macroscopic" for regional node metastasis are
      redefined as "clinically occult" and "clinically apparent"; 5) prognostic stage
      III groupings are based on N category criteria and T category criteria (ie,
      primary tumor thickness and ulceration) and increased from 3 to 4 subgroups
      (stages IIIA-IIID); 6) definitions of N subcategories are revised, with the
      presence of microsatellites, satellites, or in-transit metastases now categorized
      as N1c, N2c, or N3c based on the number of tumor-involved regional lymph nodes,
      if any; 7) descriptors are added to each M1 subcategory designation for lactate
      dehydrogenase (LDH) level (LDH elevation no longer upstages to M1c); and 8) a new
      M1d designation is added for central nervous system metastases. This evidence
      based revision of the AJCC melanoma staging system will guide patient treatment,
      provide better prognostic estimates, and refine stratification of patients
      entering clinical trials. CA Cancer J Clin 2017;67:472-492. (c) 2017 American
      Cancer Society.

PMID- 29028113
TI  - The role of PLIN protein in healthy lipid storage and lipid droplet expansion.

PMID- 29028115
TI  - Ecological correlates of seed dormancy differ among dormancy types: a case study
      in the legumes.

PMID- 29028114
TI  - Trichodysplasia spinulosa associated with HIV infection: clinical response to
      acitretin and valganciclovir.

PMID- 29028116
TI  - Effect of beta-mannanase domain from Trichoderma reesei on its biochemical
      characters and synergistic hydrolysis of sugarcane bagasse.
AB  - BACKGROUND: beta-mannanase is a key enzyme for hydrolyzing mannan, a major
      constituent of hemicellulose, which is the second most abundant polysaccharide in
      nature. Different structural domains greatly affect its biochemical characters
      and catalytic efficiency. However, the effects of linker and carbohydrate-binding
      module (CBM) on beta-mannanase from Trichoderma reesei (Man1) have not yet been
      fully described. The present study aimed to determine the influence of different
      domains on the expression efficiency, biochemical characteristics and
      hemicellulosic deconstruction of Man1. RESULTS: The expression efficiency was
      improved after truncating CBM. Activities of Man1 and Man1DeltaCBM (CBM) in the
      culture supernatant after 168 h of induction were 34.5 and 42.9 IU mL-1 ,
      although a value of only 0.36 IU mL-1 was detected for Man1DeltaLCBM (lacking CBM
      and linker). Man1 showed higher thermostability than Man1DeltaCBM at low
      temperature, whereas Man1DeltaCBM had a higher specificity for galactomannan (Km 
      = 2.5 mg mL-1 ) than Man1 (Km  = 4.0 mg mL-1 ). Both Man1 and Man1DeltaCBM could
      synergistically improve the hydrolysis of cellulose, galactomannan and pretreated
      sugarcane bagasse, with a 10-30% improvement of the reducing sugar yield.
      CONCLUSION: Linker and CBM domains were vital for mannanase activity and
      expression efficiency. CBM affected the thermostability and adsorption ability of
      Man1. The results obtained in the present study should help guide the rational
      design and directional modification of Man with respect to improving its
      catalytic efficiency. (c) 2017 Society of Chemical Industry.

PMID- 29028117
TI  - Comparison of Weight-Based Dosing Strategies for Intravenous Immunoglobulin in
      Patients with Hematologic Malignancies.
AB  - STUDY OBJECTIVE: Intravenous immunoglobulin (IVIG) is a weight-based therapy used
      to treat and prevent infections in patients with hematologic malignancies. IVIG
      doses were calculated traditionally using actual body weight (ABW). However,
      limited pharmacokinetic data suggest dosing strategies using ideal body weight
      (IBW) or adjusted body weight (adjBW) may be appropriate given the small volume
      of distribution of IVIG. Our objective was to compare the effectiveness of using
      a precision-dosing strategy (IBW or adjBW) with a traditional-dosing strategy
      (ABW) for IVIG in patients with hematologic malignancies or those undergoing
      hematopoietic stem cell transplant, as well as to perform an IVIG drug use
      analysis. DESIGN: Retrospective cohort study. SETTING: Academic medical center.
      PATIENTS: Between April 2014 and September 2016, 209 IVIG encounters met
      inclusion criteria for the primary outcome. Of those encounters, 125 were dosed
      using the traditional-dosing strategy, and 84 used the precision-dosing strategy.
      MEASUREMENTS AND MAIN RESULTS: The primary outcome was infection rate within 30
      days of IVIG administration. Secondary outcomes included 60-day infection rate,
      immunoglobulin G (IgG)-level response (IgG higher than 400 mg/dl), and realized
      and potential IVIG savings. No difference in 30-day infection rate between
      precision- and traditional-dosing strategies was identified (15.5% vs 16%,
      respectively, p=0.823). Similarly, no difference was identified in the 60-day
      infection rate between groups (23.2% vs 19.8%, respectively, p=0.568). Levels of
      IgG obtained after IVIG repletion showed a treatment response rate of 86% in both
      groups. Use of a precision-dosing strategy achieved $2600/month in institutional
      savings with the opportunity for an additional $4600/month in savings with
      complete adherence to this dosing strategy. CONCLUSION: No differences in
      infection rate and IgG-level response were identified when a precision-dosing
      strategy was used. Implementation of an IVIG precision-dosing strategy provided
      institutional cost savings.

PMID- 29028118
TI  - Elevated serum adipsin may predict unsuccessful treatment for cows' milk allergy
      but other biomarkers do not.
AB  - AIM: This study evaluated whether 15 allergy, immunology or inflammatory markers
      predicted the long-term use of cows' milk or milk products seven years after the
      start of oral immunotherapy (OIT) for cows' milk allergy in children. METHODS:
      The following laboratory parameters were measured before the OIT at Tampere
      University Hospital, Finland, and after the six-month escalation phase: serum
      total immunoglobulin (Ig) E, milk-specific IgG and IgG4, eosinophil cationic
      protein, eosinophil-derived neurotoxin, interleukins 4, 5, 6, 10 and 12p70 and
      serum adipokines adiponectin, adipsin, leptin and resistin. Follow-up data from a
      seven-year phone questionnaire in 2015 were available for 24 children: 14
      successful and 10 unsuccessful milk users. RESULTS: There were no significant
      differences in any of the 15 markers measured at the start of the study between
      the subjects who later formed the successful and unsuccessful groups. At the end
      of the six-month escalation phase of OIT, serum adipsin was higher in the group
      who were unsuccessful milk users at the seven-year follow-up study. CONCLUSION:
      None of the 15 allergy, immunology or inflammatory markers were useful in
      predicting the outcome of OIT. Preliminary evidence was found that high serum
      adipsin after the six-month escalation phase of OIT might predict unsuccessful
      outcome.

PMID- 29028119
TI  - Comparison of Treatment Persistence with Dabigatran or Rivaroxaban versus Vitamin
      K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients: A Competing
      Risk Analysis in the French National Health Care Databases.
AB  - BACKGROUND: Direct oral anticoagulants (DOACs) have been proposed as a more
      convenient alternative to vitamin K antagonists (VKAs), which are commonly
      associated with poor treatment persistence in non-valvular atrial fibrillation
      (nv-AF). METHODS: Using data from the French national health care databases
      (Regime General, 50 million beneficiaries), a cohort study was conducted to
      compare the 1-year non-persistence rates in nv-AF patients initiating dabigatran
      (N=11,141) or rivaroxaban (N=11,126) versus VKA (N=11,998). Treatment
      discontinuation was defined as a switch between oral anticoagulant (OAC) classes
      or a 60-day gap with no medication coverage, with the additional criterion of no
      reimbursement for international normalized ratio monitoring during this gap for
      VKA patients. Considering death as a competing risk, differences between 1-year
      discontinuation rates were used to compare each DOAC versus VKA. The 95%
      confidence intervals (CIs) were estimated via bootstrapping. Baseline patient
      characteristics were adjusted using inverse probability of treatment weighting.
      Subgroup analyses considered DOAC dose at initiation, age, risk of stroke, and
      bleeding. RESULTS: Adjusted 1-year discontinuation rates were higher for
      dabigatran than for VKA new users (36.8% vs 30.2%; difference: 6.6% [95% CI, 5.5
      7.6]) and for rivaroxaban versus VKA new users (33.4% vs 30.4%; 3.0% [1.9-4.1]).
      Similar differences were found in all subgroup analyses, except in dabigatran and
      rivaroxaban patients <75 years (dabigatran vs VKA: 0.3% [-1.4 to 1.8];
      rivaroxaban vs VKA: -2.6% [-4.3 to -0.9]) and dabigatran 150 mg new users (-1.1%
      [-3.1 to 0.7]). Consistent results were obtained when considering both switches
      between OAC classes and death as competing risks of treatment discontinuation.
      CONCLUSION: Results from this nationwide cohort study showed high non-persistence
      levels with all OACs and suggest that persistence with both dabigatran and
      rivaroxaban therapy is not better than persistence with VKA therapy.
      Hospitalizations for bleeding among non-persistent patients were unlikely to
      explain these high non-persistence rates.

PMID- 29028121
TI  - Lupus-like cutaneous reaction following pembrolizumab: An immune-related adverse
      event associated with anti-PD-1 therapy.
AB  - PD-1 (programmed cell death-1) inhibitors, used to treat metastatic melanoma and
      other malignancies, are associated with development of immune-related adverse
      events in the skin. Such reactions include morbilliform eruptions, vitiligo,
      alopecia areata and bullous pemphigoid. In this report, we describe a patient who
      developed a lupus-like cutaneous reaction in the setting of pembrolizumab therapy
      for metastatic melanoma, adding to the spectrum of reactions which may be
      observed in association with PD-1 inhibitor therapy.

PMID- 29028120
TI  - Rethinking the Way We Do Research: The Benefits of Community-Engaged, Citizen
      Science Approaches and Nontraditional Collaborators.
AB  - There is tremendous opportunity for basic scientists to enhance the impact of our
      research by engaging more deeply with nontraditional partners and expanding the
      way we think about interdisciplinary research teams. These efforts can include
      more deeply engaging our participants, and the broader public, in our research;
      working with individuals from other fields to take a more active role in the
      dissemination and translation of our research; and working with collaborators
      from the arts and communication sciences to make our research more engaging and
      understandable. In this review, I provide an overview of our efforts along these
      lines in a project called Spit for Science (https://spit4science.vcu.edu/). This
      project draws from concepts central to community-engaged participatory research
      and citizen science. Although conducting research in this way involves a
      considerable time commitment, it has many potential benefits, including raising
      awareness about our research areas and findings; creating a public that is more
      connected to and aware of the importance of research, which can have potential
      implications for funding for science; creating new job opportunities for
      students; and increasing participation rates in our studies. By thinking
      creatively about how we conduct our research, and more broadly engaging diverse
      groups of individuals in the research process, we have the potential to
      significantly increase the reach and impact of our science.

PMID- 29028122
TI  - Atypical ALK-positive Spitz tumors with 9p21 homozygous deletion: Report of two
      cases and review of the literature.
AB  - ALK rearrangements occur in up to 10% of spitzoid melanocytic neoplasms. No
      reported cases have shown homozygous deletion of 9p21 (CDKN2A) or gains of 6p25
      (RREB1) or 11q13 (CCND1), which have been associated with aggressive clinical
      behavior. Here we report 2 unique cases. Case 1 occurred in a 9-year-old male
      with a 14-mm nodule on the anterior left thigh. Biopsy revealed an ALK-positive
      Spitz tumor containing an irregular nodule of densely packed melanocytes with
      increased mitoses and loss of p16 immunoreactivity. FISH analysis showed
      homozygous deletion of 9p21 and gain of 6p25. Sentinel lymph node biopsy revealed
      small subcapsular foci of tumor. Case 2 occurred in a 7-year-old female with a 12
      mm nodule on the anterior right ankle. Biopsy revealed an ALK-positive Spitz
      tumor containing an expansile nodule of pleomorphic epithelioid melanocytes with
      numerous mitoses and loss of p16 immunoreactivity. By FISH, the nodule showed
      homozygous deletion of 9p21 and gains of 6p25 and 11q13. Our cases show the
      transformation of tumors produced by an activating kinase fusion gene (ALK)
      through secondary genetic changes including loss of tumor suppressor activity
      (CDKN2A). Long-term follow up will be important to further define the behavior of
      these unique Spitz tumors.

PMID- 29028112
TI  - The role of declining adaptive homeostasis in ageing.
AB  - Adaptive homeostasis is "the transient expansion or contraction of the
      homeostatic range for any given physiological parameter in response to exposure
      to sub-toxic, non-damaging, signalling molecules or events, or the removal or
      cessation of such molecules or events" (Davies, 2016). Adaptive homeostasis
      enables biological systems to make continuous short-term adjustments for optimal
      functioning despite ever-changing internal and external environments. Initiation
      of adaptation in response to an appropriate signal allows organisms to
      successfully cope with much greater, normally toxic, stresses. These short-term
      responses are initiated following effective signals, including hypoxia, cold
      shock, heat shock, oxidative stress, exercise-induced adaptation, caloric
      restriction, osmotic stress, mechanical stress, immune response, and even
      emotional stress. There is now substantial literature detailing a decline in
      adaptive homeostasis that, unfortunately, appears to manifest with ageing,
      especially in the last third of the lifespan. In this review, we present the
      hypothesis that one hallmark of the ageing process is a significant decline in
      adaptive homeostasis capacity. We discuss the mechanistic importance of
      diminished capacity for short-term (reversible) adaptive responses (both
      biochemical and signal transduction/gene expression-based) to changing internal
      and external conditions, for short-term survival and for lifespan and healthspan.
      Studies of cultured mammalian cells, worms, flies, rodents, simians, apes, and
      even humans, all indicate declining adaptive homeostasis as a potential
      contributor to age-dependent senescence, increased risk of disease, and even
      mortality. Emerging work points to Nrf2-Keap1 signal transduction pathway
      inhibitors, including Bach1 and c-Myc, both of whose tissue concentrations
      increase with age, as possible major causes for age-dependent loss of adaptive
      homeostasis.

PMID- 29028123
TI  - Impact of Insulin Detemir Administration Time on Hypoglycemia Rates in
      Hospitalized Patients.
AB  - STUDY OBJECTIVE: To determine if insulin detemir administration time affects the
      frequency of hypoglycemia (blood glucose level <70 mg/dl) in hospitalized
      patients. DESIGN: Retrospective cohort study. PATIENTS: A total of 357 adults
      (aged 18-89 yrs) who received insulin detemir for at least 48 hours while
      hospitalized between January 1, 2014, and December 31, 2015, were included.
      Patients were categorized into one of three groups according to insulin detemir
      administration time: detemir given once/day between 7 a.m. and 10 a.m. (AM group
      [71 patients]), detemir given once/day between 6 p.m. and 10 p.m. (PM group [158
      patients]), and detemir given twice/day (BID group [128 patients]). SETTING:
      Community hospital. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the
      percentage of patient days with any occurrence of hypoglycemia. The key secondary
      outcomes included the percentages of patients who experienced any hypoglycemic
      event, severe hypoglycemia, hypoglycemia requiring treatment, and refractory
      hypoglycemia; time of hypoglycemia; and percentage of patients experiencing one
      or more episodes of hyperglycemia. The AM group had a lower proportion of days
      with hypoglycemia compared with the PM group (7.9% vs 11.9%, p=0.008). There was
      a nonsignificant trend toward a lower proportion of days with hypoglycemia in the
      BID group compared with the PM group (9.1% vs 11.9%, p=0.0302). No significant
      differences in percentage of patient days with hyperglycemia and rates of severe
      hypoglycemia, hypoglycemia requiring treatment, or refractory hypoglycemia were
      noted among the three groups. CONCLUSION: Administration of detemir in the
      morning may reduce the occurrence of hypoglycemia in hospitalized patients.
      Institutions that include detemir on their formularies may consider evaluating
      the incidence of hypoglycemia and modifying administration schedules as part of
      their medication safety program.

PMID- 29028124
TI  - Atrazine feminizes sex ratio in Blanchard's cricket frogs (Acris blanchardi) at
      concentrations as low as 0.1 MUg/L.
AB  - We exposed Blanchard's cricket frogs (Acris blanchardi) to ecologically relevant
      concentrations (0, 0.1, 1, and 10 MUg/L) of a commercial formulation of atrazine
      throughout the larval period to determine effects on survival, somatic growth and
      development (time to metamorphosis and mass at metamorphosis), and gonadal
      development (sex ratio at metamorphosis and the prevalence of testicular ova in
      phenotypic males). We tested the following hypotheses: 1) atrazine feminizes the
      sex ratio, 2) atrazine increases the proportion of phenotypic males with
      testicular ova, and 3) atrazine differentially affects somatic growth (mass at
      metamorphosis) and development (time to metamorphosis) for males and females.
      Although the control sex ratio was male-biased, exposure to 0.1 and 10 MUg/L
      atrazine feminized sex ratios, because these treatments produced 51 and 55% fewer
      males than the control, respectively. We did not observe testicular ova. Atrazine
      did not impact survival or metamorphosis, and we did not detect sexually
      dimorphic impacts on time to metamorphosis or mass at metamorphosis. However,
      males metamorphosed 2.3 d later than females, regardless of treatment. Sex biases
      in timing of metamorphosis are underexplored in anurans, but if prevalent, could
      have important implications for theory surrounding the impact of environmental
      factors on metamorphosis. Our data suggest that cricket frog sex ratios are
      sensitive to environmentally relevant concentrations of atrazine and that
      feminization in the field is likely. Environ Toxicol Chem 2018;37:427-435. (c)
      2017 SETAC.

PMID- 29028125
TI  - Ledipasvir and tenofovir drug interaction in human immunodeficiency virus
      hepatitis C virus coinfected patients: Impact on tenofovir trough concentrations
      and renal safety.
AB  - We evaluate the impact of ledipasvir on both tenofovir plasma trough
      concentration and estimated glomerular renal function in human immunodeficiency
      virus-hepatitis C virus coinfected patients receiving a tenofovir-based
      antiretroviral regimen and treated with ledipasvir/sofosbuvir. Twenty-six
      patients [81% male, median age: 51 years; hepatitis C virus genotype
      1(75%)/4(15%)] were included. Tenofovir trough concentration (interquartile
      range) increased from 78 ng ml-1 (53-110) at baseline to 141 ng ml-1 (72-176) at
      1 month (P = 0.003). No significant difference on estimated glomerular renal
      function using both Cockroft-Gault and Modification of Diet in Renal Disease
      formulae, respectively, [median (interquartile range)] was observed between
      baseline [101.3 ml min-1 (91.1-114.1); 95.6 ml min-1 (86.5-111.2)], 1 month
      [102.4 ml min-1 (89.8-112.9), P = 0.26; 92.5 ml min-1 (88.1-114.3), P = 0.27],
      end-of-treatment [96.5 ml min-1 (82.4-115.4), P = 0.39; 95.4 ml min-1 (84.2
      105.4), P = 0.16] and 12 weeks after the end of treatment [100.5 ml min-1 (83.3
      111.9), P = 0.24; 93.4 ml min-1 (82.2-103.5), P = 0.16]. Three patients
      progressed from chronic kidney disease stage 1 to stage 2 at 12 weeks post
      treatment. A significant increase in tenofovir exposure through P-glycoprotein
      inhibition by ledipasvir was confirmed without significant impact on glomerular
      renal function in our population with normal renal function or mild renal
      impairment.

PMID- 29028126
TI  - Leukocytoclastic vasculitis presenting in association with Coxiella burnetii (Q
      fever): A case report.
AB  - Q fever caused by Coxiella burnetii usually presents asymptomatically or as an
      undifferentiated febrile disease and rarely as rash or other cutaneous
      manifestations of the disease. Here we present a 41-year-old male complaining of
      body ache, fever, nausea, malaise, bilateral knee pain and vomiting. Clinical
      examination revealed a notable erythematous blanching rash all over his body.
      Workup revealed positive serologic testing for C. burnetii and skin biopsy of the
      rash revealed leukocytoclastic vasculitis.

PMID- 29028127
TI  - Pure mucinous (colloid) adenocarcinoma of the conjunctiva.
AB  - Primary mucinous carcinomas of the periorbital region are very rare and often
      require differential diagnosis of metastatic disease. We describe a case of pure
      mucinous adenocarcinoma arising in the subconjunctival stroma of the ocular
      fornix in a female patient with a longstanding history of bilateral ocular
      cicatricial pemphigoid. Histologically, the tumor was composed of predominantly
      goblet-like cells floating in pools of mucin separated by delicate collagenous
      septa. The initial suspicion was of primary cutaneous mucinous carcinoma and less
      likely endocrine mucin-producing sweat gland carcinoma, however the CK7
      /synaptophysin-/chromogranin-immunoprofile did not confirm either of the two.
      Focal areas of the tumor demonstrated peripheral staining for p63 and CK5/6
      suggestive of an in situ component. Additional studies showed that the tumor
      cells were positive for CK20, CDX2, villin and MUC2. Given the final
      immunophenotype of the tumor, metastatic lesion from the lower gastrointestinal
      tract had to be ruled out. Thorough clinicoradiological work-up did not reveal
      any other primary tumors or evidence of metastatic disease elsewhere. Unique
      histomorphology, the presence of an in-situ component and negative clinical
      investigation suggest that this is a primary mucinous adenocarcinoma arising in
      the ocular fornix. This case may represent the first report of this entity in the
      literature.

PMID- 29028129
TI  - Stevens-Johnson syndrome induced by modafinil.

PMID- 29028128
TI  - Diagnostic accuracy of magnetic resonance imaging hepatic proton density fat
      fraction in pediatric nonalcoholic fatty liver disease.
AB  - : We assessed the performance of magnetic resonance imaging (MRI) proton density
      fat fraction (PDFF) in children to stratify hepatic steatosis grade before and
      after treatment in the Cysteamine Bitartrate Delayed-Release for the Treatment of
      Nonalcoholic Fatty Liver Disease in Children (CyNCh) trial, using centrally
      scored histology as reference. Participants had multiecho 1.5 Tesla (T) or 3T MRI
      on scanners from three manufacturers. Of 169 enrolled children, 110 (65%) and 83
      (49%) had MRI and liver biopsy at baseline and at end of treatment (EOT; 52
      weeks), respectively. At baseline, 17% (19 of 110), 28% (31 of 110), and 55% (60
      of 110) of liver biopsies showed grades 1, 2, and 3 histological steatosis;
      corresponding PDFF (mean +/- SD) values were 10.9 +/- 4.1%, 18.4 +/- 6.2%, and
      25.7 +/- 9.7%, respectively. PDFF classified grade 1 versus 2-3 and 1-2 versus 3
      steatosis with areas under receiving operator characteristic curves (AUROCs) of
      0.87 (95% confidence interval [CI], 0.80, 0.94) and 0.79 (0.70, 0.87),
      respectively. PDFF cutoffs at 90% specificity were 17.5% for grades 2-3 steatosis
      and 23.3% for grade 3 steatosis. At EOT, 47% (39 of 83), 41% (34 of 83), and 12%
      (10 of 83) of biopsies showed improved, unchanged, and worsened steatosis grade,
      respectively, with corresponding PDFF (mean +/- SD) changes of -7.8 +/- 6.3%, 
      1.2 +/- 7.8%, and 4.9 +/- 5.0%, respectively. PDFF change classified steatosis
      grade improvement and worsening with AUROCs (95% CIs) of 0.76 (0.66, 0.87) and
      0.83 (0.73, 0.92), respectively. PDFF change cut-off values at 90% specificity
      were -11.0% and +5.5% for improvement and worsening. CONCLUSION: MRI-estimated
      PDFF has high diagnostic accuracy to both classify and predict histological
      steatosis grade and change in histological steatosis grade in children with
      NAFLD. (Hepatology 2018;67:858-872).

PMID- 29028131
TI  - A Motion Analysis Protocol for Kinematic Assessment of Poly-Articulated
      Prosthetic Hands With Cosmetic Gloves.
AB  - To provide upper-limb amputees with devices that best fit their needs and to test
      innovative solutions, it is necessary to quantitatively appraise a device
      performance with rigorous measurement methods. The aim of this work was to define
      an optimal motion analysis protocol, suitable for optoelectronic systems, to
      measure the kinematics of poly-articulated hands even when covered by a cosmetic
      glove. This is a fundamental aspect, because gloves can decrease device speed and
      range of motion and, ultimately, patients' acceptance of the artificial limb. In
      this work, different mathematical models of the joints and marker-sets for motion
      analysis were conceived. A regression model to choose a reduced marker-set for
      studying the hand performance with different cosmetic glove models was developed.
      The proposed approaches for finger motion analysis were experimentally tested on
      the index finger of the i-Limb, a commercial myoelectric poly-articulated
      prosthetic hand, but the results can be easily extended to the whole hand and to
      other poly-articulated prosthetic hands. The methods proposed for the performance
      analysis of prosthetic hands points out that the cosmetic gloves imply a
      reduction of the finger flexion/extension (F/E) angles and of the motion
      velocity. This draws attention to the need for performing independent cyclic
      tests on commercial products with various cosmetic solutions to better guide
      component selection.

PMID- 29028130
TI  - Oral Anticoagulation and Functional Outcome after Intracerebral Hemorrhage.
AB  - OBJECTIVE: Oral anticoagulation treatment (OAT) resumption is a therapeutic
      dilemma in intracerebral hemorrhage (ICH) care, particularly for lobar
      hemorrhages related to amyloid angiopathy. We sought to determine whether OAT
      resumption after ICH is associated with long-term outcome, accounting for ICH
      location (ie, lobar vs nonlobar). METHODS: We meta-analyzed individual patient
      data from: (1) the multicenter RETRACE study (n = 542), (2) a U.S.-based single
      center ICH study (n = 261), and (3) the Ethnic/Racial Variations of Intracerebral
      Hemorrhage study (n = 209). We determined whether, within 1 year from ICH, OAT
      resumption was associated with: (1) mortality, (2) favorable functional outcome
      (modified Rankin Scale = 0-3), and (3) stroke incidence. We separately analyzed
      nonlobar and lobar ICH cases using propensity score matching and Cox regression
      models. RESULTS: We included 1,012 OAT-related ICH survivors (633 nonlobar and
      379 lobar). Among nonlobar ICH survivors, 178/633 (28%) resumed OAT, whereas
      86/379 (23%) lobar ICH survivors did. In multivariate analyses, OAT resumption
      after nonlobar ICH was associated with decreased mortality (hazard ratio [HR] =
      0.25, 95% confidence interval [CI] = 0.14-0.44, p < 0.0001) and improved
      functional outcome (HR = 4.22, 95% CI = 2.57-6.94, p < 0.0001). OAT resumption
      after lobar ICH was also associated with decreased mortality (HR = 0.29, 95% CI =
      0.17-0.45, p < 0.0001) and favorable functional outcome (HR = 4.08, 95% CI = 2.48
      6.72, p < 0.0001). Furthermore, OAT resumption was associated with decreased all
      cause stroke incidence in both lobar and nonlobar ICH (both p < 0.01).
      INTERPRETATION: These results suggest novel evidence of an association between
      OAT resumption and outcome following ICH, regardless of hematoma location. These
      findings support conducting randomized trials to explore risks and benefits of
      OAT resumption after ICH. Ann Neurol 2017;82:755-765.

PMID- 29028132
TI  - Graphene-Based Linear Tandem Micro-Supercapacitors with Metal-Free Current
      Collectors and High-Voltage Output.
AB  - Printable supercapacitors are regarded as a promising class of microscale power
      source, but are facing challenges derived from conventional sandwich-like
      geometry. Herein, the printable fabrication of new-type planar graphene-based
      linear tandem micro-supercapacitors (LTMSs) on diverse substrates with symmetric
      and asymmetric configuration, high-voltage output, tailored capacitance, and
      outstanding flexibility is demonstrated. The resulting graphene-based LTMSs
      consisting of 10 micro-supercapacitors (MSs) present efficient high-voltage
      output of 8.0 V, suggestive of superior uniformity of the entire integrated
      device. Meanwhile, LTMSs possess remarkable flexibility without obvious
      capacitance degradation under different bending states. Moreover, areal
      capacitance of LTMSs can be sufficiently modulated by incorporating polyaniline
      based pseudocapacitive nanosheets into graphene electrodes, showing enhanced
      capacitance of 7.6 mF cm-2 . To further improve the voltage output and energy
      density, asymmetric LTMSs are fabricated through controlled printing of linear
      patterned graphene as negative electrodes and MnO2 nanosheets as positive
      electrodes. Notably, the asymmetric LTMSs from three serially connected MSs are
      easily extended to 5.4 V, triple voltage output of the single cell (1.8 V),
      suggestive of the versatile applicability of this technique. Therefore, this work
      offers numerous opportunities of graphene and analogous nanosheets for one-step
      scalable fabrication of flexible tandem energy storage devices integrating with
      printed electronics on same substrate.

PMID- 29028134
TI  - Issue Information-Declaration of Helsinki.

PMID- 29028133
TI  - Addendum to "Cartilage-Specific Autophagy Deficiency Promotes ER Stress and
      Impairs Chondrogenesis in PERK-ATF4-CHOP-Dependent Manner".

PMID- 29028135
TI  - Predicting episodic and spatial memory performance from hippocampal resting-state
      functional connectivity: Evidence for an anterior-posterior division of function.
AB  - fMRI studies have identified distinct resting-state functional connectivity
      (RSFC) networks associated with the anterior and posterior hippocampus. However,
      the functional relevance of these two networks is still largely unknown.
      Hippocampal lesion studies and task-related fMRI point to a role for the anterior
      hippocampus in nonspatial episodic memory and the posterior hippocampus in
      spatial memory. We used Relevance Vector Regression (RVR), a machine-learning
      method that enables predictions of continuous outcome measures from multivariate
      patterns of brain imaging data, to test the hypothesis that patterns of whole
      brain RSFC associated with the anterior hippocampus predict episodic memory
      performance, while patterns of whole-brain RSFC associated with the posterior
      hippocampus predict spatial memory performance. Magnetic resonance imaging and
      memory assessment took place at two separate occasions. The anterior and
      posterior RSFC largely corresponded with previous findings, and showed no effect
      of laterality. Supporting the hypothesis, RVR produced accurate predictions of
      episodic performance from anterior, but not posterior, RSFC, and accurate
      predictions of spatial performance from posterior, but not anterior, RSFC. In
      contrast, a univariate approach could not predict performance from resting-state
      connectivity. This supports a functional dissociation between the anterior and
      posterior hippocampus, and indicates a multivariate relationship between
      intrinsic functional networks and cognitive performance within specific domains,
      that is relatively stable over time.

PMID- 29028136
TI  - The Synergistic Effect between Triphenylpyrrole Isomers as Donors, Linking
      Groups, and Acceptors on the Fluorescence Properties of D-pi-A Compounds in the
      Solid State.
AB  - Eight donor-pi-acceptor (D-pi-A) compounds employing triphenylpyrrole isomers
      (TPP-1,2,5 and TPP-1,3,4) as donors, malononitrile (CN) and 1H-indene-1,3(2H)
      dione (CO) as acceptors, pyridone (P) and benzopyran (B) as pi-linking groups
      were synthesized. The compounds exhibited aggregation-induced emission and
      piezochromic properties. Compared with previously reported donors,
      triphenylpyrroles induced all the compounds to have more remarkable photophysical
      properties. The compounds containing TPP-1,2,5 and P moieties displayed stronger
      fluorescence intensities, shorter emission wavelengths, and more distinct
      piezochromic properties. However, the same phenomenon was observed in the TPP
      1,3,4-containing system if B was as pi-linker. Moreover, the CN acceptor endowed
      the compound to have a relatively strong fluorescent intensity, in which CO
      induced a relatively long emission wavelength. That is, the photophysical
      properties of D-pi-A compounds can be controlled by adjusting the structure of
      donor, linker and acceptor.

PMID- 29028137
TI  - Conjugated Polymers Via Direct Arylation Polymerization in Continuous Flow:
      Minimizing the Cost and Batch-to-Batch Variations for High-Throughput Energy
      Conversion.
AB  - Continuous flow methods are utilized in conjunction with direct arylation
      polymerization (DArP) for the scaled synthesis of the roll-to-roll compatible
      polymer, poly[(2,5-bis(2-hexyldecyloxy)phenylene)-alt-(4,7-di(thiophen-2-yl)
      benzo[c][1,2,5]thiadiazole)] (PPDTBT). PPDTBT is based on simple, inexpensive,
      and scalable monomers using thienyl-flanked benzothiadiazole as the acceptor,
      which is the first beta-unprotected substrate to be used in continuous flow via
      DArP, enabling critical evaluation of the suitability of this emerging synthetic
      method for minimizing defects and for the scaled synthesis of high-performance
      materials. To demonstrate the usefulness of the method, DArP-prepared PPDTBT via
      continuous flow synthesis is employed for the preparation of indium tin oxide
      (ITO)-free and flexible roll-coated solar cells to achieve a power conversion
      efficiency of 3.5% for 1 cm2 devices, which is comparable to the performance of
      PPDTBT polymerized through Stille cross coupling. These efforts demonstrate the
      distinct advantages of the continuous flow protocol with DArP avoiding use of
      toxic tin chemicals, reducing the associated costs of polymer upscaling, and
      minimizing batch-to-batch variations for high-quality material.

PMID- 29028138
TI  - 2D Ruddlesden-Popper Perovskites for Optoelectronics.
AB  - Conventional 3D organic-inorganic halide perovskites have recently undergone
      unprecedented rapid development. Yet, their inherent instabilities over moisture,
      light, and heat remain a crucial challenge prior to the realization of
      commercialization. By contrast, the emerging 2D Ruddlesden-Popper-type
      perovskites have recently attracted increasing attention owing to their great
      environmental stability. However, the research of 2D perovskites is just in their
      infancy. In comparison to 3D analogues, they are natural quantum wells with a
      much larger exciton binding energy. Moreover, their inner structural, dielectric,
      optical, and excitonic properties remain to be largely explored, limiting further
      applications. This review begins with an introduction to 2D perovskites, along
      with a detailed comparison to 3D counterparts. Then, a discussion of the organic
      spacer cation engineering of 2D perovskites is presented. Next, quasi-2D
      perovskites that fall between 3D and 2D perovskites are reviewed and compared.
      The unique excitonic properties, electron-phonon coupling, and polarons of 2D
      perovskites are then be revealed. A range of their (opto)electronic applications
      is highlighted in each section. Finally, a summary is given, and the strategies
      toward structural design, growth control, and photophysics studies of 2D
      perovskites for high-performance electronic devices are rationalized.

PMID- 29028139
TI  - Birth-weight discordance and neonatal morbidity in twin pregnancy: analysis of
      STORK multiple pregnancy cohort.
AB  - OBJECTIVES: To investigate the relationship between weight discordance and
      neonatal morbidity in twin pregnancy progressing to at least 34 weeks of
      gestation. The secondary aim was to determine the predictive accuracy of
      different weight discordance cut-offs in predicting neonatal morbidity in twin
      pregnancy. METHODS: This was a retrospective multicenter cohort study of all twin
      pregnancies booked for antenatal care at four hospitals in the Southwest Thames
      region of London Obstetric Research Collaborative (STORK) over a period of 10
      years. Ultrasound data were obtained by a search of each hospital's obstetric
      ultrasound computer database, while outcome details were obtained from the
      computerized maternity and neonatal records. The primary outcome was incidence of
      composite neonatal morbidity in twin pregnancy with birth-weight discordance.
      Logistic regression was used to identify and adjust for potential confounders,
      while a receiver-operating characteristics (ROC) curve was used to determine
      predictive accuracy. RESULTS: Nine hundred and thirty-nine twin pregnancies (760
      dichorionic, 179 monochorionic) were included. Gestational age at birth and birth
      weight decile were significantly lower in pregnancies complicated by neonatal
      morbidity compared with those which were not (P < 0.001 for both). On
      multivariable logistic regression analysis, gestational age at birth (P < 0.001),
      birth-weight decile (P = 0.029) and birth-weight discordance (P = 0.019), but not
      chorionicity (P = 0.477) or presence of at least one small-for-gestational-age
      (SGA) twin (P = 0.245), were associated independently with the risk of neonatal
      morbidity. There was a progressive increase in the risk of neonatal morbidity
      with increasing birth-weight discordance. Despite this association, birth-weight
      discordance showed an overall poor predictive accuracy for neonatal morbidity,
      with an area under the ROC curve of 0.58 (95% CI, 0.53-0.63) with an optimal cut
      off of 17.6%, showing sensitivity and specificity of 35.2% (95% CI, 27.8-43.2%)
      and 83.2% (95% CI, 80.4-85.8%), respectively. CONCLUSION: Intertwin birth-weight
      discordance is associated independently with the risk of neonatal morbidity in
      twins born after 34 weeks' gestation, irrespective of chorionicity or diagnosis
      of SGA in either twin. However, its predictive accuracy for neonatal morbidity is
      poor. Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 29028141
TI  - Mapping trends in the concept of nurse rounding: A bibliometric analysis and
      research agenda.
AB  - AIMS: Examine the growth and diffusion of research on the concept of nurse
      rounding and provide definitional clarity on forms of nurse rounding. METHODS:
      Bibliometric and content analysis of primary research on nurse rounding were used
      to map development of the field. Manuscripts were identified from a keyword
      search of MEDLINE, CINAHL, and PsycINFO databases for the period 2000 to 2015.
      Titles, country of origin, and year of publication along with details on the
      characteristics and sample of each study were coded on a database. Content
      analyses were performed on the coded data to derive a taxonomic understanding and
      identify publication trends. RESULTS: Thirty-eight primary research studies were
      identified. Overall, there has been an increase in the number and diversity of
      studies on nursing rounding. A typology of 4 variants of nurse rounding was
      devised to enhance clarity and enable comparative analysis. CONCLUSION: There has
      been continued interest in nurse rounding and its potential benefits. However,
      poor definitional clarity is evident in this body of research, with various label
      used interchangeably in studies reporting similar rounding designs. The field
      would benefit from improved conceptual clarity and investigation into forms of
      nurse rounding that remain largely unexamined.

PMID- 29028140
TI  - Report of 12 cases with tracheobronchial mucormycosis and a review.
AB  - OBJECTIVES: Tracheobronchial mucormycosis is a rare and invasive pulmonary
      mucormycosis involving the tracheobronchial tree. DATA SOURCE: At a 3500-bed
      tertiary care center. STUDY SELECTION: This was a retroactive study of 12 cases
      of tracheobronchial mucormycosis diagnosed in our hospital, and 48 cases that
      were previously reported in the English literature. RESULTS: Rhizopus was the
      predominant species of pathogen (66.7%). Primary bronchus was the most frequently
      involved location (38.2%), and upper lobes (51% of cases) were a predilection.
      Obstructive necrosis and mucosal necrosis were the most common pathological forms
      (40% and 34.5%, respectively). Fever (59.3%), cough (59.3%), dyspnea (40.7%) and
      hemoptysis (30.5%) were the most common symptoms. 51.4% patients had rales, 40%
      had moist rales and 28.6% had negative physical findings. Ninety-five percent
      patients had immunosuppressive diseases. Diabetes mellitus (66.7%), diabetes
      ketoacidosis (21.7%), corticosteroid therapy (20%) and kidney insufficiency
      (18.3%) were the most common predisposing factors. 13.2% had neutropenia which
      was mostly among the non-diabetic patients (P = .006). Endobronchial lesion of
      23.2% had imaging reports with 33.9% exhibiting single mass. Pathological
      diagnosis of 76.7% used the transbronchial biopsy. The most frequent antifungal
      therapies were intravenous amphotericin B (79.7%), surgery (33.3%) and surgery
      combined with amphotericin B therapy (28.3%). Overall in-hospital mortality was
      52.5%, with hemoptysis (P = .017), dyspnea at presentation (P = .022) and
      angioinvasion (P = .03) as independent risk prognostic factors. In contrast,
      surgery (P = .003) was an independent protection prognostic factor. CONCLUSIONS:
      Tracheobronchial mucormycosis is a rare but severe disease with high mortality
      because of its nonspecific clinical presentations and variable predisposing
      factors.

PMID- 29028142
TI  - Local hyperthermia therapy for refractory cutaneous Mycobacterium marinum
      infection.

PMID- 29028143
TI  - Functional analysis of Toxoplasma lactate dehydrogenases suggests critical roles
      of lactate fermentation for parasite growth in vivo.
AB  - Glycolysis was thought to be the major pathway of energy supply in both fast
      replicating tachyzoites and slowly growing bradyzoites of Toxoplasma gondii.
      However, its biological significance has not been clearly verified. The genome of
      T. gondii encodes two lactate dehydrogenases (LDHs), which are differentially
      expressed in tachyzoites and bradyzoites. In this study, we knocked out the two
      LDH genes individually and in combination and found that neither gene was
      required for tachyzoite growth in vitro under standard growth conditions.
      However, during infection in mice, Deltaldh1 and Deltaldh1 Deltaldh2 mutants were
      unable to propagate and displayed significant virulence attenuation and cyst
      formation defects. LDH2 only played minor roles in these processes. To further
      elucidate the mechanisms underlying the critical requirement of LDH in vivo, we
      found that Deltaldh1 Deltaldh2 mutants replicated significantly more slowly than
      wild-type parasites when cultured under conditions with physiological levels of
      oxygen (3%). In addition, Deltaldh1 Deltaldh2 mutants were more susceptible to
      the oxidative phosphorylation inhibitor oligomycin A. Together these results
      suggest that lactate fermentation is critical for parasite growth under
      physiological conditions, likely because energy production from oxidative
      phosphorylation is insufficient when oxygen is limited and lactate fermentation
      becomes a key supplementation.

PMID- 29028144
TI  - Treatment of pediatric anogenital condyloma acuminata with sinecatechins
      ointment.

PMID- 29028145
TI  - Ultrafast Dynamics of a Fluorescent Tetrazolium Compound in Solution.
AB  - Tetrazolium salts are exploited in various fields of research by virtue of their
      low reduction potentials. Increasingly, associated applications also attend to
      the photochemical and luminescence properties of these systems. Here, we
      investigate the photoinduced dynamics of phenyl-benzo[c]tetrazolo-cinnolinium
      chloride (PTC), one of the very few known fluorescent tetrazolium compounds, by
      using time-correlated single-photon counting, femtosecond fluorescence
      upconversion, and ultrafast transient absorption spectroscopy. PTC is generated
      photochemically by ultraviolet illumination of 2,3,5-triphenyl-tetrazolium
      chloride (TTC) in various alcohols. Time-resolved fluorescence measurements on
      PTC with different excitation wavelengths disclose biphasic solvation and
      vibrational relaxation dynamics. Depending on the solvent, the emission behavior
      of PTC is characterized by quantum yields on the order of several tens of percent
      and corresponding excited-state lifetimes of several hundreds of picoseconds. The
      radiative rate is basically constant for the studied alcohols, whereas the rate
      of the competing non-radiative process is sensitive to the solvent polarity.
      Hence, we discuss the possible involvement of intermediate radicals and further
      presumptive reaction pathways pursued after photoexcitation of PTC.

PMID- 29028146
TI  - Ferromagnetism and Half-Metallicity in a High-Band-Gap Hexagonal Boron Nitride
      System.
AB  - Metal-free half-metallicity is the subject of intense research in the field of
      spintronics devices. Using density functional theoretical calculations, atom-thin
      hexagonal boron nitride (h-BN)-based systems are studied for possible spintronics
      applications. Ferromagnetism is observed in patterned C-doped h-BN systems.
      Interestingly, such a patterned C-doped h-BN exhibits half-metallicity with a
      Curie temperature of approximately 324 K at a particular C-doping concentration.
      It shows half-metallicity more than metal-free systems studied to date. Thus,
      such a BN-based system can be used to achieve a 100 % spin-polarised current at
      the Fermi level. Furthermore, this C-doped system shows excellent dynamical,
      thermal, and mechanical properties. Therefore, a stable metal-free planar
      ferromagnetic half-metallic h-BN-based system is proposed for use in room
      temperature spintronics devices.

PMID- 29028147
TI  - 'Most significant change' and the maximising cognition (MAXCOG) intervention: The
      views of clients, supporters and counsellors.
AB  - OBJECTIVES: To explore the views of clients, supporters and counsellors about
      their experiences of the maximising cognition (MAXCOG) intervention. METHODS: The
      most significant change (MSC) method of analysis was used. Twenty-three narrative
      accounts of the MAXCOG intervention and the 'MSC' that occurred were obtained. A
      panel, including experts from Alzheimer's Australia, the MAXCOG research team and
      clinicians from memory clinics, conducted a workshop to discuss and categorise
      the accounts. RESULTS: Two subcategories of stories were identified: (i) An
      'acceptance group' that focused on adjustment issues; and (ii) A 'goal
      achievement' group with a focus on goals and improvement in ability and
      confidence. These subcategories mapped closely to the original goals outlined for
      the MAXCOG intervention. CONCLUSION: The MAXCOG intervention was successful in
      assisting people to work towards goals and adjust psychologically to
      difficulties.

PMID- 29028149
TI  - Solitary perianal rectal mass as the only manifestation of Crohn's disease.

PMID- 29028148
TI  - Follow-up of 1887 patients receiving tumor necrosis-alpha antagonists: Tuberculin
      skin test conversion and tuberculosis risk.
AB  - OBJECTIVES: To evaluate the characteristics of patients who developed
      tuberculosis while receiving tumor necrosis factor-alpha (TNF-alpha) antagonists
      and the related factors with tuberculosis. METHODS: Patient's demographics,
      tuberculin skin test (TST), isoniazid prophylaxis and type of TNF-alpha
      antagonist were recorded. TST conversion (>=5 mm increase) was evaluated for
      patients who had baseline and 1-year TST. RESULTS: Files of 1887 patients who
      were receiving TNF-alpha antagonists between August 2005 and June 2015 were
      evaluated. TST significantly increased at the end of 1 year (n = 748
      baseline:7.36 +/- 7.2 mm vs. 1 year:9.52 +/- 7.5 mm, P < 0.001). One-third of
      patients (31.2%) who had negative TST at baseline had positive TST at 1 year.
      Tuberculosis developed in 22 patients (1.16%). The annual incidence of
      tuberculosis was 423/100 000 patient-year. TNF-alpha antagonist indications were
      ankylosing spondylitis (n = 8), inflammatory bovel diseases (n = 7) and
      rheumatoid arthritis (n = 4). Ten (45.5%) patients received infliximab, six
      (27.3%) patients received etanercept and six (27.3%) patients received
      adalimumab. Nineteen (86.4%) patients were under isoniazid prophylaxis. Twelve
      patients had extrapulmonary tuberculosis (54.5%; four lymph node, three pleura,
      two periton, one pericarditis, one intestinal, one joint). Atypical mycobacterium
      was detected in one patient. Adalimumab treatment (9.5* increase), male sex
      (15.6* increase) and previous tuberculosis disease history (11.5* increase) were
      risk factors for active tuberculosis. Conversion of TST was not found related
      with tuberculosis. CONCLUSIONS: Despite the high proportion of isoniazid
      prophylaxis, the incidence of tuberculosis in our patients receiving TNF-alpha
      antagonist was higher than the literature. Adalimumab treatment, male sex and
      previous tuberculosis disease history were found as risk factors for
      tuberculosis.

PMID- 29028150
TI  - Potential of microRNAs as novel targets in the alleviation of pathological fear.
AB  - The current treatment of post-traumatic stress disorder (PTSD), phobias and other
      anxiety disorders, remains insufficient particularly in producing long-lasting
      full symptom control. Dysfunctional fear processing is common in these disorders,
      including a deficiency in fear-inhibitory mechanisms and impairment in the
      ability to discriminate between safety and danger cues. Research has aimed to
      elucidate brain circuitries, neurotransmitters and downstream signaling pathways
      important in the alleviation of aberrant fear, with a specific focus on
      mechanisms modulating fear memory and its behavioral expression. MicroRNAs
      (miRNA) as "fine tuners" of gene expression at the post-transcriptional level
      have emerged as critical regulators of such mechanisms important in both, the
      generation and the inhibition of fear memories. Along these lines, abnormal
      expression of miRNAs has been associated with different fear-related disorders.
      After providing an updated overview on the involvement of miRNAs in fear learning
      mechanisms, we summarize and discuss in particular those studies in which the
      implication of miRNAs in successful inhibition of fear has been explored. For a
      better overview, we dissociate the different modes of fear alleviation
      investigated in this regard and present studies in rodents demonstrating that
      specific miRNAs are involved in the destabilization of fear by interfering with
      consolidation/reconsolidation mechanisms or that they are associated with the
      generation of fear extinction or safety learning. Finally, we discuss the
      potential of miRNAs as biomarkers and novel therapeutic targets, as well as the
      challenges involved in applying the discovered mechanisms in the development of
      improved treatments of fear- and trauma-related disorders.

PMID- 29028151
TI  - Delirium care: Real-world solutions to real-world problems.
AB  - OBJECTIVES: Implementation research into delirium care is lacking. Exploiting
      known practice barriers to understand what management strategies work best in
      delirium is a means of prioritising care interventions. A consensus approach to
      determining priority interventions in delirium was derived and related to
      reference standards in health-care practice. METHODS: A workshop of 20 experts
      was held at the Australasian Delirium Association conference 2016. Structured
      small group work, iterative ranking and a 21-member check were undertaken to (i)
      explore research barriers in delirium care; (ii) explore how barriers related to
      individual items of multicomponent interventions; and (iii) rank multicomponent
      interventions in relation to each statement within the newly released Australian
      Commission on Safety and Quality in Health Care delirium standard. RESULTS: Top
      ranking interventions included the following: education and training,
      comprehensive geriatric assessment, family partnerships, individualised care and
      multidisciplinary engagement. CONCLUSION: Delirium experts identified a minimum
      standard of any care intervention for delirium.

PMID- 29028152
TI  - Salivary C-reactive protein and mean platelet volume in diagnosis of late-onset
      neonatal pneumonia.
AB  - BACKGROUND: Neonatal pneumonia is an important and major cause of neonatal
      morbidity and mortality worldwide therefore; its early detection plays a crucial
      role in successful therapy. Analysis of saliva as a non-invasive method for
      detection of neonatal diseases holds great promise for improving health care.
      Till now, salivary C-reactive protein (CRP), mean platelet volume (MPV),
      neutrophil/lymphocyte ratio (NLR) and platelets/lymphocytes ratio (PLR) have not
      been studied as markers of diagnosis in neonatal pneumonia. OBJECTIVE: To assess
      the applicability of salivary CRP, MPV, NLR and PLR as diagnostic markers in late
      onset neonatal pneumonia. METHODS: A prospective case control study of 70 full
      term neonates, 35 with late-onset neonatal pneumonia and 35 healthy controls, was
      enrolled. Serum and salivary CRP concentrations were measured by ELISA, while
      MPV, NLR and PLR were measured by automated blood cell counter. RESULTS: This
      study showed a statistically significant difference between salivary CRP means in
      neonates with late-onset neonatal pneumonia vs control neonates (6.2 +/- 4.6 and
      2.8 +/- 1.9 ng/L) respectively. At the cutoff point of 3.8 ng/L, salivary CRP
      showed 91.4% sensitivity and 80.9% specificity. Salivary CRP also showed accuracy
      in predicting elevated serum CRP in neonates with pneumonia. MPV showed a
      significant difference between pneumonia and controls (mean = 10.2 +/- 0.7, 8 +/-
      0.5) respectively. At cutoff point 9.0, it has 80% sensitivity and specificity.
      CONCLUSIONS: The present study showed for the first time that both salivary CRP
      and MPV are suitable as diagnostic markers in late-onset neonatal pneumonia.

PMID- 29028153
TI  - Tailored intraoperative localization of non-palpable pulmonary lesions for
      thoracoscopic wedge resection using hybrid room technology.
AB  - INTRODUCTION: VATS wedge resection can require conversion to thoracotomy when
      pulmonary lesions cannot be identified. Hybrid operating rooms (HORs) provide
      real-time image acquisition capabilities allowing the intraoperative placement of
      markers to facilitate the removal of non-palpable nodules during VATS.
      OBJECTIVES: To present our workflow based on the alternative use of two different
      markers according to the location of the lung lesion and report our initial
      results. METHODS: All consecutive patients with non-palpable lesions requiring
      VATS wedge resection underwent localization of the targets in HOR. Lesions were
      considered non-palpable if they were small (<1 cm), deep (>1 cm from surface),
      subsolid, or located within a dystrophic area. Anesthetized patients were placed
      in lateral decubitus. Cone-beam CT (CBCT) was performed, and the needle
      trajectory was planned using Syngo iGuide Needle Guidance. Metal hook-wire or
      coil was placed, according to our workflow, close to the lesion and their
      position was verified by CBCT or fluoroscopy. RESULTS: Eleven VATS wedge
      resections were performed in 10 patients with 12 non-palpable lesions. The
      localization was performed with seven hook-wires and four coils in 30 minutes
      (range 17-56 minutes). The median estimated total effective dose was 11.6 mSv
      (range 1.9-24.7 mSv). Eleven lesions were removed by VATS, and one deep nodule
      required a thoracotomy. No complications were observed. CONCLUSIONS: Our
      experience confirms that HOR is suitable for simultaneous localization and VATS
      resection of 'difficult' pulmonary lesions. A versatile approach, using different
      devices, seems advisable for the removal of targets in every clinical scenario,
      reducing the VATS conversion rate.

PMID- 29028154
TI  - On-Surface Synthesis of Adenine Oligomers via Ullmann Reaction.
AB  - Despite the fact that DNA bases have been well-studied on surface, the on-surface
      synthesis of one-dimensional DNA analogs through in situ reactions is still an
      interesting topic to be investigated. Herein, from the interplay of high
      resolution scanning tunneling microscopy (STM) imaging and density functional
      theory (DFT) calculations, we have delicately designed a halogenated derivative
      of adenine as precursor to realize the combination of DNA bases and Ullmann
      reaction, and then successfully synthesized adenine oligomers on Au(111) via
      Ullmann coupling. This model system provides a possible bottom-up strategy of
      fabricating adenine oligomers on surface, which may further give access to man
      made DNA strands with multiple bases.

PMID- 29028155
TI  - A Parallel Reaction Monitoring Mass Spectrometric Method for Analysis of
      Potential CSF Biomarkers for Alzheimer's Disease.
AB  - SCOPE: The aim of this study was to develop and evaluate a parallel reaction
      monitoring mass spectrometry (PRM-MS) assay consisting of a panel of potential
      protein biomarkers in cerebrospinal fluid (CSF). EXPERIMENTAL DESIGN: Thirteen
      proteins were selected based on their association with neurodegenerative diseases
      and involvement in synaptic function, secretory vesicle function, or innate
      immune system. CSF samples were digested and two to three peptides per protein
      were quantified using stable isotope-labeled peptide standards. RESULTS:
      Coefficients of variation were generally below 15%. Clinical evaluation was
      performed on a cohort of 10 patients with Alzheimer's disease (AD) and 15 healthy
      subjects. Investigated proteins of the granin family exhibited the largest
      difference between the patient groups. Secretogranin-2 (p<0.005) and
      neurosecretory protein VGF (p<0.001) concentrations were lowered in AD. For
      chromogranin A, two of three peptides had significantly lowered AD concentrations
      (p<0.01). The concentrations of the synaptic proteins neurexin-1 and neuronal
      pentraxin-1, as well as neurofascin were also significantly lowered in AD
      (p<0.05). The other investigated proteins, beta2-microglobulin, cystatin C,
      amyloid precursor protein, lysozyme C, neurexin-2, neurexin-3, and neurocan core
      protein, were not significantly altered. CONCLUSION AND CLINICAL RELEVANCE: PRM
      MS of protein panels is a valuable tool to evaluate biomarker candidates for
      neurodegenerative disorders.

PMID- 29028156
TI  - Genetic background effects in Neuroligin-3 mutant mice: Minimal behavioral
      abnormalities on C57 background.
AB  - : Neuroligin-3 (NLGN3) is a postsynaptic cell adhesion protein that interacts
      with presynaptic ligands including neurexin-1 (NRXN1) [Ichtchenko et al., Journal
      of Biological Chemistry, 271, 2676-2682, 1996]. Mice harboring a mutation in the
      NLGN3 gene (NL3R451C) mimicking a mutation found in two brothers with autism
      spectrum disorder (ASD) were previously generated and behaviorally phenotyped for
      autism-related behaviors. In these NL3R451C mice generated and tested on a hybrid
      C57BL6J/129S2/SvPasCrl background, we observed enhanced spatial memory and
      reduced social interaction [Tabuchi et al., Science, 318, 71-76, 2007].
      Curiously, an independently generated second line of mice harboring the same
      mutation on a C57BL6J background exhibited minimal aberrant behavior, thereby
      providing apparently discrepant results. To investigate the origin of the
      discrepancy, we previously replicated the original findings of Tabuchi et al. by
      studying the same NL3R451C mutation on a pure 129S2/SvPasCrl genetic background.
      Here we complete the behavioral characterization of the NL3R451C mutation on a
      pure C57BL6J genetic background to determine if background genetics play a role
      in the discrepant behavioral outcomes involving NL3R451C mice. NL3R451C mutant
      mice on a pure C57BL6J background did not display spatial memory enhancements or
      social interaction deficits. We only observed a decreased startle response and
      mildly increased locomotor activity in these mice suggesting that background
      genetics influences behavioral outcomes involving the NL3R451C mutation. Autism
      Res 2018, 11: 234-244. (c) 2017 International Society for Autism Research, Wiley
      Periodicals, Inc. LAY SUMMARY: Behavioral symptoms of autism can be highly
      variable, even in cases that involve identical genetic mutations. Previous
      studies in mice with a mutation of the Neuroligin-3 gene showed enhanced learning
      and social deficits. We replicated these findings on the same and different
      genetic backgrounds. In this study, however, the same mutation in mice on a
      different genetic background did not reproduce our previous findings. Our results
      suggest that genetic background influences behavioral symptoms of this autism
      associated mutation.

PMID- 29028157
TI  - Transthoracic catheter drainage for large symptomatic congenital pulmonary airway
      malformation.
AB  - BACKGROUND: Surgical resection of large symptomatic congenital pulmonary airway
      malformation (CPAM) in newborns has high risks of mortality and postoperative
      morbidity. This study aimed to report the clinical outcomes of newborns who
      underwent percutaneous transthoracic catheter drainage (PTCD) of large
      symptomatic CPAM before surgical resection. METHODS: This was a retrospective,
      descriptive study based on review of the medical records of newborn infants who
      required surgical resection of large symptomatic CPAM at a single tertiary
      hospital from 2001 to 2017. The clinical outcomes were compared between patients
      who underwent surgical resection following PTCD (PTCD group) and those who
      underwent surgical resection alone (non-PTCD group). RESULTS: A total of 17
      newborns were included. PTCD was performed in seven cases; the median age at the
      time of the initial PTCD was 4 days (range, 0-20 days). Following PTCD in all
      cases, chest radiograph demonstrated a dramatic reduction in the sizes of the
      cysts and improvement of mediastinal shift and the Alveolar-arterial oxygen
      difference decreased. The median duration between initial PTCD and surgery was 4
      days (range, 2-33 days). PTCD-related complications included pneumothorax (n =
      2), catheter displacement (n = 1), and failure to drain (n = 1). Compared with
      the non-PTCD group (6 of 10), the PTCD group had a tendency toward lower rates of
      postoperative complications (1 of 7). CONCLUSION: PTCD can be an effective
      interim management for symptomatic newborn infants who require emergency surgical
      resection of large CPAM.

PMID- 29028158
TI  - Effects of intratracheal budesonide during early postnatal life on lung maturity
      of premature fetal rabbits.
AB  - AIM: This study aimed to study the effects of intratracheal instillation of
      budesonide on lung maturity of premature fetal rabbits. The developmental pattern
      of pulmonary alveoli in rabbits is similar to that in humans. METHOD: Fetal
      rabbits were taken out from female rabbits on the 28th day of pregnancy (full
      term = 31 days) by cesarean section (c-section). The fetal rabbits were divided
      into four groups: control (normal saline, NS), budesonide (budesonide, BUD), calf
      pulmonary surfactant for injection (pulmonary surfactant, PS), and calf pulmonary
      surfactant + budesonide for injection (pulmonary surfactant + budesonide, PS +
      BUD). All premature rabbits were kept warm after c-section. After 15-min
      autonomous respiration, a tracheal cannula was implemented for instilling NS,
      BUD, PS, and PS + BUD. The morphology of lung tissues of premature fetal rabbits
      was analyzed using optical and electron microscopes. Surfactant protein B (SP-B)
      mRNA and protein levels in lung tissues were determined using polymerase chain
      reaction and Western blotting, respectively. RESULT: Intratracheal instillation
      of BUD could increase the alveolar area of the fetal rabbits (P < 0.01), decrease
      the alveolar wall thickness (P < 0.01), and increase the mean density of lamellar
      bodies (P < 0.05) and SP-B protein levels in type II epithelial cells of
      pulmonary alveoli (P < 0.05). CONCLUSION: Intratracheal instillation of BUD
      during early postnatal life is effective in promoting alveolarization and
      increasing SP-B expression, the pro-pulmonary maturity of BUD combined with PS is
      superior to that of BUD or PS alone. However, the long-term effect of BUD on lung
      development needs further exploration.

PMID- 29028159
TI  - Serologically diagnosed acute human bocavirus 1 infection in childhood community
      acquired pneumonia.
AB  - AIM: To assess the role of human bocavirus 1 (HBoV1) as a causative agent of non
      severe community-acquired pneumonia (CAP) in children. METHODS: Patients aged 2
      59 months with non-severe CAP (respiratory complaints and radiographic pulmonary
      infiltrate/consolidation) attending a University Hospital in Salvador, Brazil
      were enrolled in a prospective cohort. From 820 recruited children in a clinical
      trial (ClinicalTrials.gov NCT01200706), nasopharyngeal aspirate (NPA), and acute
      and convalescent serum samples were obtained from 759 (92.6%) patients. NPAs were
      tested for 16 respiratory viruses by PCR. Acute HBoV1 infection was confirmed by
      measuring specific IgM and IgG responses in paired serum samples. RESULTS:
      Respiratory viruses were detected in 693 (91.3%; 95%CI: 89.1-93.2) CAP cases by
      PCR. HBoV1-DNA was detected in 159 (20.9%; 95%CI: 18.2-24.0) cases. Of these 159
      PCR positive cases, acute HBoV1 infection was confirmed serologically in 38 cases
      (23.9%; 95%CI: 17.8-31.0). Overall, acute HBoV1 infection was confirmed in 5.0%
      (38/759) of non-severe CAP patients. HBoV1 was detected in 151 cases with at
      least one other virus making 31.7% of all multiple virus (n = 477) detections.
      Among all 759 cases, 216 had one respiratory virus detected, and sole HBoV1 was
      detected in only 8 (3.7%). Acute HBoV1 infection was serologically diagnosed in
      34 (22.5%) HBoV1-DNA-positive cases with another virus, compared to 4 (50.0%)
      cases with sole virus detection (p = 0.09). CONCLUSION: HBoV1 was detected by PCR
      in one fifth of the children with non-severe CAP and acute HBoV1 infection was
      serologically confirmed in one quarter of these cases.

PMID- 29028162
TI  - The benefits of replication research.

PMID- 29028160
TI  - Angiotensin-converting enzyme insertion/deletion gene polymorphism in Egyptian
      children with CAP: A case-control study.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of childhood
      morbidity and mortality worldwide. The angiotensin-converting enzyme (ACE) gene
      is a potential candidate gene for CAP risk. OBJECTIVES: In this study, we aimed
      to investigate whether the ACE insertion/deletion (I/D) polymorphism (rs4340)
      could be a genetic marker for CAP susceptibility in Egyptian children, and we
      also measured the serum ACE level to assess its relation to such polymorphism.
      METHODS: This was a prospective case-control study included 300 patients with
      CAP, and 300 age, gender, and ethnicity matched healthy controls. The ACE I/D
      polymorphism (rs4340) at intron 16 was genotyped by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP), while the serum ACE levels
      were measured by ELISA. RESULTS: Compared to the controls subjects, the
      frequencies of the ACE DD genotype and D allele were overrepresented in patients
      with CAP (OR = 3.05; [95%CI: 2.14-4.35] for the DD genotype; P < 0.001) and (OR:
      1.8; [95%CI: 1.42-2.29]; for the D allele; P < 0.01, respectively). Patients with
      the DD genotype had significantly higher mean serum ACE levels (45.6 +/- 11.4
      U/L) compared to those with ID genotype (36.5 +/- 8.3 U/L) and II genotype (21.6
      +/- 5.7 U/L); P < 0.01, respectively. CONCLUSION: The ACE I/D polymorphism
      (rs4340) may contribute to the genetic susceptibility of CAP in Egyptian
      children. The ACE D allele and DD genotype were associated with higher serum ACE
      levels among studied CAP patients.

PMID- 29028161
TI  - Effect of haemodialysis and residual renal function on serum levels of galectin
      3, B-type natriuretic peptides and cardiac troponin T.
AB  - AIM: Levels of plasma markers of myocardial fibrosis (galectin-3), stretch (B
      type natriuretic peptide (BNP)) and injury (high-sensitivity troponin T (hs-TnT))
      are affected by haemodialysis, residual renal function (RRF) and cardiac
      pathology. We aimed to determine the association of RRF, urine output and
      haemodialysis itself on cardiac biomarkers in haemodialysis patients. METHODS:
      Adult haemodialysis patients underwent venesection pre- and post-haemodialysis
      then echocardiography and inter-dialytic urine collection to calculate RRF
      (mL/min per 1.73m2 ) and urine output (mL/day). Galectin-3, BNP-32, NT-ProBNP and
      hs-TnT levels were compared across tertiles of echocardiographic parameters, RRF
      and urine output using the non-parametric test for trend across ordered groups.
      RESULTS: Twenty-three patients (17 male) with mean age 67.7+/-13.8 years and
      median (interquartile range) dialysis duration 13.6 (9.8-19.1) months
      participated. Galectin-3 was substantially lower following haemodialysis: 55
      ng/mL (47-70) versus 23 ng/mL (19-27, P < 0.001), but other biomarkers changed
      little. By increasing RRF tertile, post-dialysis galectin-3 was 32.6 ng/mL (23.7
      36.6), 21.9 ng/mL (19.0-23.2) and 19.0 ng/mL (16.9-21.0, P = 0.001); NT-ProBNP
      was 10 192 ng/L (2303-21 504), 2037 ng/L (1224-10 795) and 1481 ng/L (172-2890, P
      = 0.016). Results were similar for daily urine volume, but measured
      echocardiographic parameters were not associated with biomarker concentrations.
      CONCLUSION: Plasma concentration of galectin-3 is reduced by the haemodialysis
      procedure. Lower RRF and urine volume are strongly associated with higher levels
      of galectin-3 and NT-Pro-BNP. These associations are important to the clinical
      interpretation of these biomarker levels in haemodialysis patients.

PMID- 29028163
TI  - Early Detection of Urinary Proteome Biomarkers for Effective Early Treatment of
      Pulmonary Fibrosis in a Rat Model.
AB  - SCOPE: Pulmonary fibrosis (PF) is a progressive and devastating lung disease.
      With limited effective treatments available in the late stage, PF has a very poor
      prognosis. Molecular biomarkers are highly desired for PF, especially for its
      early phase. MATERIALS AND METHODS: Urine is a good biomarker source, and
      accumulates systemic changes in the body especially in the early-stage of
      diseases. In this study, a bleomycin (BLM)-induced rat model is used to mimic PF.
      Using labeled proteome quantitation, some urinary proteins are identified as
      candidate biomarkers of PF for early detection and disease monitoring. Then,
      prednisone treatment is administered at different phases of fibrosis. RESULTS:
      Our results suggested that urine proteins could enable early detection and
      monitoring of both disease progression and treatment efficacy in the BLM-induced
      PF model. Early prednisone treatment effectively inhibited pulmonary fibrosis,
      whereas the same treatment at a later phase had very limited effects. Meanwhile,
      five proteins showed the potential for monitoring therapeutic response.
      CONCLUSION: Urinary proteomics has been underutilized in respiratory diseases.
      These findings will improve our understanding of the pathogenesis of PF and
      accelerate biomarker discovery in respiratory diseases.

PMID- 29028164
TI  - Executive summary of the 9th meeting of the WHO working group RT-PCR for the
      detection and subtyping of influenza viruses.

PMID- 29028165
TI  - Executive summary of the 6th meeting of the WHO Expert Working Group of the GISRS
      for Surveillance  of Antiviral Susceptibility.

PMID- 29028166
TI  - Continuing risk of meningitis due to Neisseria meningitidis serogroup C in
      Africa: revised recommendations from a WHO expert consultation.

PMID- 29028167
TI  - Progress towards eliminating onchocerciasis in the WHO Region of the Americas:
      elimination of transmission in the north-east focus of the Bolivarian Republic of
      Venezuela.

PMID- 29028168
TI  - Synthesis of a Pentasaccharide Fragment Related to the Inner Core Region of
      Rhizobial and Agrobacterial Lipopolysaccharides.
AB  - The pentasaccharide fragment alpha-d-Man-(1 -> 5)-[alpha-d-Kdo-(2 -> 4)-]alpha-d
      Kdo-(2 -> 6)-beta-d-GlcNAc-(1 -> 6)-alpha-d-GlcNAc equipped with a 3-aminopropyl
      spacer moiety was prepared by a sequential assembly of monosaccharide building
      blocks. The glucosamine disaccharide-as a backbone surrogate of the bacterial
      lipid A region-was synthesized using an 1,3-oxazoline donor, which was followed
      by coupling with an isopropylidene-protected Kdo-fluoride donor to afford a
      protected tetrasaccharide intermediate. Eventually, an orthogonally protected
      manno-configured trichloroacetimidate donor was used to achieve the sterically
      demanding glycosylation of the 5-OH group of Kdo in good yield. The resulting
      pentasaccharide is suitably protected for further chain elongation at positions
      3, 4, and 6 of the terminal mannose. Global deprotection afforded the target
      pentasaccharide to be used for the conversion into neoglycoconjugates and
      "clickable" ligands.

PMID- 29028169
TI  - Aggregation Number in Water/n-Hexanol Molecular Clusters Formed in Cyclohexane at
      Different Water/n-Hexanol/Cyclohexane Compositions Calculated by Titration 1H
      NMR.
AB  - Upon titration of n-hexanol/cyclohexane mixtures of different molar compositions
      with water, water/n-hexanol clusters are formed in cyclohexane. Here, we develop
      a new method to estimate the water and n-hexanol aggregation numbers in the
      clusters that combines integration analysis in one-dimensional 1H NMR spectra,
      diffusion coefficients calculated by diffusion-ordered NMR spectroscopy, and
      further application of the Stokes-Einstein equation to calculate the hydrodynamic
      volume of the clusters. Aggregation numbers of 5-15 molecules of n-hexanol per
      cluster in the absence of water were observed in the whole range of n
      hexanol/cyclohexane molar fractions studied. After saturation with water,
      aggregation numbers of 6-13 n-hexanol and 0.5-5 water molecules per cluster were
      found. O-H and O-O atom distances related to hydrogen bonds between
      donor/acceptor molecules were theoretically calculated using density functional
      theory. The results show that at low n-hexanol molar fractions, where a robust
      hydrogen-bond network is held between n-hexanol molecules, addition of water
      makes the intermolecular O-O atom distance shorter, reinforcing molecular
      association in the clusters, whereas at high n-hexanol molar fractions, where
      dipole-dipole interactions dominate, addition of water makes the intermolecular O
      O atom distance longer, weakening the cluster structure. This correlates with
      experimental NMR results, which show an increase in the size and aggregation
      number in the clusters upon addition of water at low n-hexanol molar fractions,
      and a decrease of these magnitudes at high n-hexanol molar fractions. In
      addition, water produces an increase in the proton exchange rate between
      donor/acceptor molecules at all n-hexanol molar fractions.

PMID- 29028170
TI  - Mediating Reductive Charge Shift Reactions in Electron Transport Chains.
AB  - We report the synthesis of a full-fledged family of covalent electron donor
      acceptor1-acceptor2 conjugates and their charge-transfer characterization by
      means of advanced photophysical assays. By virtue of variable excited state
      energies and electron donor strengths, either Zn(II)Porphyrins or
      Zn(II)Phthalocyanines were linked to different electron-transport chains
      featuring pairs of electron accepting fullerenes, that is, C60 and C70. In this
      way, a fine-tuned redox gradient is established to power a unidirectional, long
      range charge transport from the excited-state electron donor via a transient C60*
      toward C70*-. This strategy helps minimize energy losses in the reductive, short
      range charge shift from C60 to C70. At the forefront of our investigations are
      excited-state dynamics deduced from femtosecond transient absorption
      spectroscopic measurements and subsequent computational deconvolution of the
      transient absorption spectra. These provide evidence for cascades of short-range
      charge-transfer processes, including reductive charge shift reactions between the
      two electron-accepting fullerenes, and for kinetics that are influenced by the
      nature and length of the respective spacer. Of key importance is the postulate of
      a mediating state in the charge-shift reaction at weak electronic couplings. Our
      results point to an intimate relationship between triplet-triplet energy transfer
      and charge transfer.

PMID- 29028172
TI  - Influences of Histidine-1 and Azaphenylalanine-4 on the Affinity, Anti
      inflammatory, and Antiangiogenic Activities of Azapeptide Cluster of
      Differentiation 36 Receptor Modulators.
AB  - Azapeptide analogues of growth hormone releasing peptide-6 (GHRP-6) exhibit
      promising affinity, selectivity, and modulator activity on the cluster of
      differentiation 36 receptor (CD36). For example, [A1, azaF4]- and [azaY4]-GHRP-6
      (1a and 2b) were previously shown to bind selectively to CD36 and exhibited
      respectively significant antiangiogenic and slight angiogenic activities in a
      microvascular sprouting assay using choroid explants. The influences of the 1-
      and 4-position residues on the affinity, anti-inflammatory, and antiangiogenic
      activity of these azapeptides have now been studied in detail by the synthesis
      and analysis of a set of 25 analogues featuring Ala1 or His1 and a variety of
      aromatic side chains at the aza-amino acid residue in the 4-position. Although
      their binding affinities differed only by a factor of 17, the analogues exhibited
      significant differences in ability to modulate production of nitric oxide (NO) in
      macrophages and choroidal neovascularization.

PMID- 29028171
TI  - Structure-Based Design of Non-natural Macrocyclic Peptides That Inhibit Protein
      Protein Interactions.
AB  - Macrocyclic peptides can interfere with challenging biomolecular targets
      including protein-protein interactions. Whereas there are various approaches that
      facilitate the identification of peptide-derived ligands, their evolution into
      higher affinity binders remains a major hurdle. We report a virtual screen based
      on molecular docking that allows the affinity maturation of macrocyclic peptides
      taking non-natural amino acids into consideration. These macrocycles bear large
      and flexible substituents that usually complicate the use of docking approaches.
      A virtual library containing more than 1400 structures was screened against the
      target focusing on docking poses with the core structure resembling a known
      bioactive conformation. Based on this screen, a macrocyclic peptide 22 involving
      two non-natural amino acids was evolved showing increased target affinity and
      biological activity. Predicted binding modes were verified by X-ray
      crystallography. The presented workflow allows the screening of large macrocyclic
      peptides with diverse modifications thereby expanding the accessible chemical
      space and reducing synthetic efforts.

PMID- 29028175
TI  - The Information Content of Discrete Functions and Their Application in Genetic
      Data Analysis.
AB  - The complex of central problems in data analysis consists of three components:
      (1) detecting the dependence of variables using quantitative measures, (2)
      defining the significance of these dependence measures, and (3) inferring the
      functional relationships among dependent variables. We have argued previously
      that an information theory approach allows separation of the detection problem
      from the inference of functional form problem. We approach here the third
      component of inferring functional forms based on information encoded in the
      functions. We present here a direct method for classifying the functional forms
      of discrete functions of three variables represented in data sets. Discrete
      variables are frequently encountered in data analysis, both as the result of
      inherently categorical variables and from the binning of continuous numerical
      variables into discrete alphabets of values. The fundamental question of how much
      information is contained in a given function is answered for these discrete
      functions, and their surprisingly complex relationships are illustrated. The all
      important effect of noise on the inference of function classes is found to be
      highly heterogeneous and reveals some unexpected patterns. We apply this
      classification approach to an important area of biological data analysis-that of
      inference of genetic interactions. Genetic analysis provides a rich source of
      real and complex biological data analysis problems, and our general methods
      provide an analytical basis and tools for characterizing genetic problems and for
      analyzing genetic data. We illustrate the functional description and the classes
      of a number of common genetic interaction modes and also show how different modes
      vary widely in their sensitivity to noise.

PMID- 29028176
TI  - A Biclique Approach to Reference-Anchored Gene Blocks and Its Applications to
      Genomic Islands.
AB  - We formalize a new problem variant in gene-block discovery, denoted Reference
      Anchored Gene Blocks (RAGB), given a query sequence Q of length n, representing
      the gene array of a DNA element, a window size bound d on the length of a
      substring of interest in Q, and a set of target gene sequences [Formula: see
      text]. Our objective is to identify gene blocks in [Formula: see text] that are
      centered in a subset q of co-localized genes from Q, and contain genomes from
      [Formula: see text] in which the corresponding orthologs of the genes from q are
      also co-localized. We cast RAGB as a variant of a (colored) biclique problem in
      bipartite graphs, and analyze its parameterized complexity, as well as the
      parameterized complexity of other related problems. We give an [Formula: see
      text] time algorithm for the uncolored variant of our biclique problem, where m
      is the number of areas of interest that are parsed from the target sequences, and
      n and d are as defined earlier. Our algorithm can be adapted to compute all
      maximal bicliques in the graph within the same time complexity, and to handle
      edge weights with a slight [Formula: see text] increase to its time complexity.
      For the colored version of the problem, our algorithm has a time complexity of
      [Formula: see text]. We implement the algorithm and exemplify its application to
      the data mining of proteobacterial gene blocks that are centered in predicted
      proteobacterial genomic islands, leading to the identification of putatively
      mobilized clusters of virulence, pathogenicity, and resistance genes.

PMID- 29028174
TI  - Could Frequent Carbapenem Use Be a Risk Factor for Colistin Resistance?
AB  - AIMS: The antibiotic colistin, which had been previously abandoned, is being
      brought back as a last line of defense against bacterial infection. However,
      colistin resistance was reported shortly after its reintroduction. This study
      evaluated the risk factors for colonization/infections due to colistin-resistant
      Acinetobacter baumannii (ColR-Ab) and Klebsiella pneumoniae (ColR-Kp) strains and
      characterized the molecular epidemiology of these two strains. RESULTS: Age,
      previous hospitalization duration, and previous use of carbapenem and colistin
      were risk factors for ColR-Kp, whereas previous use of carbapenem and colistin
      was a risk factor for ColR-Ab. According to pulsed-field gel electrophoresis
      analysis, most ColR-Kp strains could be grouped into two major pulsotypes. This
      appears to be an indicator of cross contamination of ColR-Kp strain, since
      different isolates appeared to be belonging to the same clones. The existence of
      colistin-susceptible (ColS) and colistin-resistant (ColR) strains in the same
      pulsotypes might also be an indicator of the recent emergence of resistance
      mechanisms. CONCLUSIONS: The results highlight the emergence of ColR pathogens in
      Turkey, which is considered to be developing country, and that carbapenem use
      coupled with insufficient infection control measures might increase the risk of
      ColR outbreaks.

PMID- 29028177
TI  - Postmeal increment in intact glucagon-like peptide 1 level, but not intact
      glucose-dependent insulinotropic polypeptide levels, is inversely associated with
      metabolic syndrome in patients with type 2 diabetes.
AB  - PURPOSE: Metabolic syndrome increases the risk of cardiovascular disease.
      Recently glucagon-like peptide 1 (GLP-1) agonists proved to be effective in
      preventing cardiovascular disease (CVD) in patients with type 2 diabetes. We
      investigated the association of blood incretin levels with metabolic syndrome in
      patients with type 2 diabetes. MATERIALS AND METHODS: This is a cross-sectional
      study involving 334 people with type 2 diabetes. Intact GLP-1 (iGLP-1) and intact
      glucose-dependent insulinotropic polypeptide (iGIP) levels were measured in a
      fasted state and 30 min after ingestion of a standard mixed meal. Metabolic
      syndrome was diagnosed based on the criteria of the International Diabetes
      Federation. RESULTS: Two hundred twenty-five (69%) of the subjects have metabolic
      syndrome. The fasting iGLP-1 level was no different between groups. Thirty-min
      postprandial iGLP-1 was non-significantly lower in the subjects who had metabolic
      syndrome. Incremental iGLP-1 (DeltaiGLP-1, the difference between 30-min postmeal
      and fasting iGLP-1 levels) was significantly lower in those with metabolic
      syndrome. There were no significant differences in fasting iGIP, postprandial
      iGIP, and DeltaiGIP between groups. The DeltaiGLP-1, but not DeltaiGIP levels
      decreased significantly as the number of metabolic syndrome components increased.
      In hierarchical logistic regression analysis, the DeltaiGLP-1 level was found to
      be a significant contributor to metabolic syndrome even after adjusting for other
      covariates. CONCLUSION: Taken together, the iGLP-1 increment in the 30 min after
      meal ingestion is inversely associated with metabolic syndrome in patients with
      type 2 diabetes. This suggests that postmeal iGLP-1 increment could be useful in
      assessing cardiovascular risk in type 2 diabetes.

PMID- 29028178
TI  - Zika Virus: Immune Evasion Mechanisms, Currently Available Therapeutic Regimens,
      and Vaccines.
AB  - The sudden emergence of infectious pathogens such as Zika virus (ZIKV) holds
      global health concerns. Recent dissemination of ZIKV from Pacific to Americas
      with an upsurge of congenital anomalies and Guillain Barre Syndrome (GBS) in
      adults has created an alarming situation. High-throughput studies are in progress
      to understand ZIKV's mode of pathogenesis and mechanism of immune escape, yet the
      pathogenesis remains obscure. Mainly ZIKV's envelope (E) protein and
      nonstructural proteins (mainly NS1 and NS5) manipulate host cell to support viral
      immune escape by modulation of the interferon pathway and complement antagonism.
      The development of direct therapeutics for ZIKV infection is required to overcome
      the rapidly evolving viral threat. Currently, the existing strategies for ZIKV
      treatment are only supportive. Although, there is no prophylactic or therapeutic
      vaccine presently available, however, recent efforts have brought up ZIKV
      vaccines into clinical trial phase 1. This review presents the highlights of
      recent advances in understanding immune evasion strategies adapted by ZIKV and
      existing therapies against the virus.

PMID- 29028179
TI  - Reconstructing One-Articulated Networks with Distance Matrices.
AB  - Given a distance matrix M that represents evolutionary distances between any two
      species, an edge-weighted phylogenetic network N is said to satisfy M if between
      any pair of species, there exists a path in N with a length equal to the
      corresponding entry in M. In this article, we consider a special class of
      networks called a one-articulated network, which is a proper superset of galled
      trees. We show that if the distance matrix M is derived from an ultrametric one
      articulated network N (i.e., for any species X and Y, the entry [Formula: see
      text] is equal to the shortest distance between X and Y in N), we can re
      construct a network that satisfies M in [Formula: see text] time, where n denotes
      the number of species; further, the reconstructed network is guaranteed to be the
      simplest, in a sense that the number of hybrid nodes is minimized. In addition,
      one may easily index a one-articulated network N with a minimum number of hybrid
      nodes in [Formula: see text] space, such that on any given phylogenetic tree T,
      we can determine whether T is contained in N (i.e., if a spanning subtree
      [Formula: see text] of N is a subdivision of T) in [Formula: see text] time.

PMID- 29028180
TI  - Stakeholder Education for Community-Wide Health Initiatives: A Focus on Teen
      Pregnancy Prevention.
AB  - Teen pregnancies and births continue to decline due in part to implementation of
      evidence-based interventions and clinical strategies. While local stakeholder
      education is also thought to be critical to this success, little is known about
      what types of strategies work best to engage stakeholders. With the goal of
      identifying and describing evidence-based or best practice strategies for
      stakeholder education in community-based public health initiatives, we conducted
      a systematic literature review of strategies used for effective stakeholder
      education. Over 400 articles were initially retrieved; 59 articles met inclusion
      criteria. Strategies were grouped into four steps that communities can use to
      support stakeholder education efforts: identify stakeholder needs and resources,
      develop a plan, develop tailored and compelling messaging, and use implementation
      strategies. These strategies lay a framework for high-quality stakeholder
      education. In future research, it is important to prioritize evaluating specific
      activities taken to raise awareness, educate, and engage a community in community
      wide public health efforts.

PMID- 29028181
TI  - Unbiased Taxonomic Annotation of Metagenomic Samples.
AB  - The classification of reads from a metagenomic sample using a reference taxonomy
      is usually based on first mapping the reads to the reference sequences and then
      classifying each read at a node under the lowest common ancestor of the candidate
      sequences in the reference taxonomy with the least classification error. However,
      this taxonomic annotation can be biased by an imbalanced taxonomy and also by the
      presence of multiple nodes in the taxonomy with the least classification error
      for a given read. In this article, we show that the Rand index is a better
      indicator of classification error than the often used area under the receiver
      operating characteristic (ROC) curve and F-measure for both balanced and
      imbalanced reference taxonomies, and we also address the second source of bias by
      reducing the taxonomic annotation problem for a whole metagenomic sample to a set
      cover problem, for which a logarithmic approximation can be obtained in linear
      time and an exact solution can be obtained by integer linear programming.
      Experimental results with a proof-of-concept implementation of the set cover
      approach to taxonomic annotation in a next release of the TANGO software show
      that the set cover approach further reduces ambiguity in the taxonomic annotation
      obtained with TANGO without distorting the relative abundance profile of the
      metagenomic sample.

PMID- 29028182
TI  - Hypothesis: RNA and DNA Viral Sequence Integration into the Mammalian Host Genome
      Supports Long-Term B Cell and T Cell Adaptive Immunity.
AB  - Viral sequence integration into the mammalian genome has long been perceived as a
      health risk. In some cases, integration translates to chronic viral infection,
      and in other instances, oncogenic gene mutations occur. However, research also
      shows that animal cells can benefit from integrated viral sequences (e.g., to
      support host cell development or to silence foreign invaders). Here we propose
      that, comparable with the clustered regularly interspaced short palindromic
      repeats that provide bacteria with adaptive immunity against invasive
      bacteriophages, animal cells may co-opt integrated viral sequences to support
      immune memory. We hypothesize that host cells express viral peptides from open
      reading frames in integrated sequences to boost adaptive B cell and T cell
      responses long after replicating viruses are cleared. In support of this
      hypothesis, we examine previous literature describing (1) viruses that infect
      acutely (e.g., vaccinia viruses and orthomyxoviruses) followed by unexplained,
      long-term persistence of viral nucleotide sequences, viral peptides, and virus
      specific adaptive immunity, (2) the high frequency of endogenous viral genetic
      elements found in animal genomes, and (3) mechanisms with which animal host
      machinery supports foreign sequence integration.

PMID- 29028185
TI  - Time-Varying Time-Frequency Complexity Measures for Epileptic EEG Data Analysis.
AB  - OBJECTIVE: Our goal is to use existing and to propose new time-frequency entropy
      measures that objectively evaluate the improvement on epileptic patients after
      medication by studying their resting state electroencephalography (EEG)
      recordings. An increase in the complexity of the signals would confirm an
      improvement in the general state of the patient. METHODS: We review the Renyi
      entropy based on time-frequency representations, along with its time-varying
      version. We also discuss the entropy based on singular value decomposition
      computed from a time-frequency representation, and introduce its corresponding
      time-dependant version. We test these quantities on synthetic data. Friedman
      tests are used to confirm the differences between signals (before and after
      proper medication). Principal component analysis is used for dimensional
      reduction prior to a simple threshold discrimination. RESULTS: Experimental
      results show a consistent increase in complexity measures in the different
      regions of the brain. These findings suggest that extracted features can be used
      to monitor treatment. When combined, they are useful for classification purposes,
      with areas under ROC curves higher than 0.93 in some regions. CONCLUSION: Here we
      applied time-frequency complexity measures to resting state EEG signals from
      epileptic patients for the first time. We also introduced a new time-varying
      complexity measure. We showed that these features are able to evaluate the
      treatment of the patient, and to perform classification. SIGNIFICANCE: The time
      frequency complexities, and their time-varying versions, can be used to monitor
      the treatment of epileptic patients. They could be applied to a wider range of
      problems.

PMID- 29028183
TI  - Non-synaptic signaling from cerebellar climbing fibers modulates Golgi cell
      activity.
AB  - Golgi cells are the principal inhibitory neurons at the input stage of the
      cerebellum, providing feedforward and feedback inhibition through mossy fiber and
      parallel fiber synapses. In vivo studies have shown that Golgi cell activity is
      regulated by climbing fiber stimulation, yet there is little functional or
      anatomical evidence for synapses between climbing fibers and Golgi cells. Here,
      we show that glutamate released from climbing fibers activates ionotropic and
      metabotropic receptors on Golgi cells through spillover-mediated transmission.
      The interplay of excitatory and inhibitory conductances provides flexible control
      over Golgi cell spiking, allowing either excitation or a biphasic sequence of
      excitation and inhibition following single climbing fiber stimulation. Together
      with prior studies of spillover transmission to molecular layer interneurons,
      these results reveal that climbing fibers exert control over inhibition at both
      the input and output layers of the cerebellar cortex.

PMID- 29028186
TI  - Decoding Covert Somatosensory Attention by a BCI System Calibrated With Tactile
      Sensation.
AB  - OBJECTIVE: We propose a novel calibration strategy to facilitate the decoding of
      covert somatosensory attention by exploring the oscillatory dynamics induced by
      tactile sensation. METHODS: It was hypothesized that the similarity of the
      oscillatory pattern between stimulation sensation (SS, real sensation) and
      somatosensory attentional orientation (SAO) provides a way to decode covert
      somatic attention. Subjects were instructed to sense the tactile stimulation,
      which was applied to the left (SS-L) or the right (SS-R) wrist. The brain
      computer interface (BCI) system was calibrated with the sensation data and then
      applied for online SAO decoding. RESULTS: Both SS and SAO showed oscillatory
      activation concentrated on the contralateral somatosensory hemisphere. Offline
      analysis showed that the proposed calibration method led to a greater accuracy
      than the traditional calibration method based on SAO only. This is confirmed by
      online experiments, where the online accuracy on 15 subjects was 78.8 +/- 13.1%,
      with 12 subjects >70% and 4 subject >90%. CONCLUSION: By integrating the stimulus
      induced oscillatory dynamics from sensory cortex, covert somatosensory attention
      can be reliably decoded by a BCI system calibrated with tactile sensation.
      SIGNIFICANCE: Indeed, real tactile sensation is more consistent during
      calibration than SAO. This brain-computer interfacing approach may find
      application for stroke and completely locked-in patients with preserved somatic
      sensation.

PMID- 29028187
TI  - Dynamic Video Deblurring Using a Locally Adaptive Blur Model.
AB  - State-of-the-art video deblurring methods cannot handle blurry videos recorded in
      dynamic scenes since they are built under a strong assumption that the captured
      scenes are static. Contrary to the existing methods, we propose a new video
      deblurring algorithm that can deal with general blurs inherent in dynamic scenes.
      To handle general and locally varying blurs caused by various sources, such as
      moving objects, camera shake, depth variation, and defocus, we estimate pixel
      wise varying non-uniform blur kernels. We infer bidirectional optical flows to
      handle motion blurs, and also estimate Gaussian blur maps to remove optical blur
      from defocus. Therefore, we propose a single energy model that jointly estimates
      optical flows, defocus blur maps and latent frames. We also provide a framework
      and efficient solvers to minimize the proposed energy model. By optimizing the
      energy model, we achieve significant improvements in removing general blurs,
      estimating optical flows, and extending depth-of-field in blurry frames.
      Moreover, in this work, to evaluate the performance of non-uniform deblurring
      methods objectively, we have constructed a new realistic dataset with ground
      truths. In addition, extensive experimental results on publicly available
      challenging videos demonstrate that the proposed method produces qualitatively
      superior performance than the state-of-the-art methods which often fail in either
      deblurring or optical flow estimation.

PMID- 29028188
TI  - Zero-Shot Learning Using Synthesised Unseen Visual Data with Diffusion
      Regularisation.
AB  - Sufficient training examples are the fundamental requirement for most of the
      learning tasks. However, collecting well-labelled training examples is costly.
      Inspired by Zero-shot Learning (ZSL) that can make use of visual attributes or
      natural language semantics as an intermediate level clue to associate low-level
      features with high-level classes, in a novel extension of this idea, we aim to
      synthesise training data for novel classes using only semantic attributes.
      Despite the simplicity of this idea, there are several challenges. First, how to
      prevent the synthesised data from over-fitting to training classes? Second, how
      to guarantee the synthesised data is discriminative for ZSL tasks? Third, we
      observe that only a few dimensions of the learnt features gain high variances
      whereas most of the remaining dimensions are not informative. Thus, the question
      is how to make the concentrated information diffuse to most of the dimensions of
      synthesised data. To address the above issues, we propose a novel embedding
      algorithm named Unseen Visual Data Synthesis (UVDS) that projects semantic
      features to the high-dimensional visual feature space. Two main techniques are
      introduced in our proposed algorithm. (1) We introduce a latent embedding space
      which aims to reconcile the structural difference between the visual and semantic
      spaces, meanwhile preserve the local structure. (2) We propose a novel Diffusion
      Regularisation (DR) that explicitly forces the variances to diffuse over most
      dimensions of the synthesised data. By an orthogonal rotation (more precisely, an
      orthogonal transformation), DR can remove the redundant correlated attributes and
      further alleviate the over-fitting problem. On four benchmark datasets, we
      demonstrate the benefit of using synthesised unseen data for zero-shot learning.
      Extensive experimental results suggest that our proposed approach significantly
      outperforms the state-of-the-art methods.

PMID- 29028184
TI  - Native KCC2 interactome reveals PACSIN1 as a critical regulator of synaptic
      inhibition.
AB  - KCC2 is a neuron-specific K+-Cl- cotransporter essential for establishing the Cl-
      gradient required for hyperpolarizing inhibition in the central nervous system
      (CNS). KCC2 is highly localized to excitatory synapses where it regulates spine
      morphogenesis and AMPA receptor confinement. Aberrant KCC2 function contributes
      to human neurological disorders including epilepsy and neuropathic pain. Using
      functional proteomics, we identified the KCC2-interactome in the mouse brain to
      determine KCC2-protein interactions that regulate KCC2 function. Our analysis
      revealed that KCC2 interacts with diverse proteins, and its most predominant
      interactors play important roles in postsynaptic receptor recycling. The most
      abundant KCC2 interactor is a neuronal endocytic regulatory protein termed
      PACSIN1 (SYNDAPIN1). We verified the PACSIN1-KCC2 interaction biochemically and
      demonstrated that shRNA knockdown of PACSIN1 in hippocampal neurons increases
      KCC2 expression and hyperpolarizes the reversal potential for Cl-. Overall, our
      global native-KCC2 interactome and subsequent characterization revealed PACSIN1
      as a novel and potent negative regulator of KCC2.

PMID- 29028189
TI  - Non-Rigid Event-by-Event Continuous Respiratory Motion Compensated List-Mode
      Reconstruction for PET.
AB  - Respiratory motion during positron emission tomography (PET)/computed tomography
      (CT) imaging can cause significant image blurring and underestimation of tracer
      concentration for both static and dynamic studies. In this paper, with the aim to
      eliminate both intra-cycle and inter-cycle motions, and apply to dynamic imaging,
      we developed a non-rigid event-by-event (NR-EBE) respiratory motion-compensated
      list-mode reconstruction algorithm. The proposed method consists of two
      components: the first component estimates a continuous non-rigid motion field of
      the internal organs using the internal-external motion correlation. This
      continuous motion field is then incorporated into the second component, non-rigid
      MOLAR (NR-MOLAR) reconstruction algorithm to deform the system matrix to the
      reference location where the attenuation CT is acquired. The point spread
      function (PSF) and time-of-flight (TOF) kernels in NR-MOLAR are incorporated in
      the system matrix calculation, and therefore are also deformed according to
      motion. We first validated NR-MOLAR using a XCAT phantom with a simulated
      respiratory motion. NR-EBE motion-compensated image reconstruction using both the
      components was then validated on three human studies injected with 18F-FPDTBZ and
      one with 18F-fluorodeoxyglucose (FDG) tracers. The human results were compared
      with conventional non-rigid motion correction using discrete motion field (NR
      discrete, one motion field per gate) and a previously proposed rigid EBE motion
      compensated image reconstruction (R-EBE) that was designed to correct for rigid
      motion on a target lesion/organ. The XCAT results demonstrated that NR-MOLAR
      incorporating both PSF and TOF kernels effectively corrected for non-rigid
      motion. The 18F-FPDTBZ studies showed that NR-EBE out-performed NR-Discrete, and
      yielded comparable results with R-EBE on target organs while yielding superior
      image quality in other regions. The FDG study showed that NR-EBE clearly improved
      the visibility of multiple moving lesions in the liver where some of them could
      not be discerned in other reconstructions, in addition to improving
      quantification. These results show that NR-EBE motion-compensated image
      reconstruction appears to be a promising tool for lesion detection and
      quantification when imaging thoracic and abdominal regions using PET.

PMID- 29028190
TI  - A Hybrid Solution for Simultaneous Transfer of Ultrastable Optical Frequency, RF
      Frequency, and UTC Time-Tags Over Optical Fiber.
AB  - We describe a fiber-optic solution for simultaneous distribution of all signals
      generated at today's most advanced time and frequency laboratories, i.e., an
      ultrastable optical reference frequency derived from an optical atomic clock, a
      radio frequency precisely linked to a realization of the SI-Second, and a
      realization of an atomic timescale, being the local representation of the
      virtual, global UTC timescale. In our solution both the phase of the optical
      carrier and the delay of electrical signals (10-MHz frequency reference and one
      pulse-per-second time tags) are stabilized against environmental perturbations
      influencing the fiber link instability and accuracy. We experimentally
      demonstrate optical transfer stabilities of and for 100 s averaging period, for
      optical carrier and 10-MHz signals, respectively.

PMID- 29028191
TI  - Deep Neural Networks for No-Reference and Full-Reference Image Quality
      Assessment.
AB  - We present a deep neural network-based approach to image quality assessment
      (IQA). The network is trained end-to-end and comprises ten convolutional layers
      and five pooling layers for feature extraction, and two fully connected layers
      for regression, which makes it significantly deeper than related IQA models.
      Unique features of the proposed architecture are that: 1) with slight adaptations
      it can be used in a no-reference (NR) as well as in a full-reference (FR) IQA
      setting and 2) it allows for joint learning of local quality and local weights,
      i.e., relative importance of local quality to the global quality estimate, in an
      unified framework. Our approach is purely data-driven and does not rely on hand
      crafted features or other types of prior domain knowledge about the human visual
      system or image statistics. We evaluate the proposed approach on the LIVE, CISQ,
      and TID2013 databases as well as the LIVE In the wild image quality challenge
      database and show superior performance to state-of-the-art NR and FR IQA methods.
      Finally, cross-database evaluation shows a high ability to generalize between
      different databases, indicating a high robustness of the learned features.

PMID- 29028192
TI  - Reversion Correction and Regularized Random Walk Ranking for Saliency Detection.
AB  - In recent saliency detection research, many graph-based algorithms have applied
      boundary priors as background queries, which may generate completely "reversed"
      saliency maps if the salient objects are on the image boundaries. Moreover, these
      algorithms usually depend heavily on pre-processed superpixel segmentation, which
      may lead to notable degradation in image detail features. In this paper, a novel
      saliency detection method is proposed to overcome the above issues. First, we
      propose a saliency reversion correction process, which locates and removes the
      boundary-adjacent foreground superpixels, and thereby increases the accuracy and
      robustness of the boundary prior-based saliency estimations. Second, we propose a
      regularized random walk ranking model, which introduces prior saliency estimation
      to every pixel in the image by taking both region and pixel image features into
      account, thus leading to pixel-detailed and superpixel-independent saliency maps.
      Experiments are conducted on four well-recognized data sets; the results indicate
      the superiority of our proposed method against 14 state-of-the-art methods, and
      demonstrate its general extensibility as a saliency optimization algorithm. We
      further evaluate our method on a new data set comprised of images that we define
      as boundary adjacent object saliency, on which our method performs better than
      the comparison methods.

PMID- 29028193
TI  - Landmark-Based Shape Encoding and Sparse-Dictionary Learning in the Continuous
      Domain.
AB  - We provide a generic framework to learn shape dictionaries of landmark-based
      curves that are defined in the continuous domain. We first present an unbiased
      alignment method that involves the construction of a mean shape as well as
      training sets whose elements are subspaces that contain all affine
      transformations of the training samples. The alignment relies on orthogonal
      projection operators that have a closed form. We then present algorithms to learn
      shape dictionaries according to the structure of the data that needs to be
      encoded: 1) projection-based functional principal-component analysis for
      homogeneous data and 2) continuous-domain sparse shape encoding to learn
      dictionaries that contain imbalanced data, outliers, or different types of shape
      structures. Through parametric spline curves, we provide a detailed and exact
      implementation of our method. We demonstrate that it requires fewer parameters
      than purely discrete methods and that it is computationally more efficient and
      accurate. We illustrate the use of our framework for dictionary learning of
      structures in biomedical images as well as for shape analysis in bioimaging.

PMID- 29028194
TI  - Temporal Scalability of Dynamic Volume Data Using Mesh Compensated Wavelet
      Lifting.
AB  - Due to their high resolution, dynamic medical 2D+t and 3D+t volumes from computed
      tomography (CT) and magnetic resonance tomography (MR) reach a size which makes
      them very unhandy for teleradiologic applications. A lossless scalable
      representation offers the advantage of a down-scaled version which can be used
      for orientation or previewing, while the remaining information for reconstructing
      the full resolution is transmitted on demand. The wavelet transform offers the
      desired scalability. A very high quality of the lowpass sub-band is crucial in
      order to use it as a down-scaled representation. We propose an approach based on
      compensated wavelet lifting for obtaining a scalable representation of dynamic CT
      and MR volumes with very high quality. The mesh compensation is feasible to model
      the displacement in dynamic volumes which is mainly given by expansion and
      contraction of tissue over time. To achieve this, we propose an optimized
      estimation of the mesh compensation parameters to optimally fit for dynamic
      volumes. Within the lifting structure, the inversion of the motion compensation
      is crucial in the update step. We propose to take this inversion directly into
      account during the estimation step and can improve the quality of the lowpass sub
      band by 0.63 and 0.43 dB on average for our tested dynamic CT and MR volumes at
      the cost of an increase of the rate by 2.4% and 1.2% on average.

PMID- 29028195
TI  - Tensor Rank Preserving Discriminant Analysis for Facial Recognition.
AB  - Facial recognition, one of the basic topics in computer vision and pattern
      recognition, has received substantial attention in recent years. However, for
      those traditional facial recognition algorithms, the facial images are reshaped
      to a long vector, thereby losing part of the original spatial constraints of each
      pixel. In this paper, a new tensor-based feature extraction algorithm termed
      tensor rank preserving discriminant analysis (TRPDA) for facial image recognition
      is proposed; the proposed method involves two stages: in the first stage, the low
      dimensional tensor subspace of the original input tensor samples was obtained; in
      the second stage, discriminative locality alignment was utilized to obtain the
      ultimate vector feature representation for subsequent facial recognition. On the
      one hand, the proposed TRPDA algorithm fully utilizes the natural structure of
      the input samples, and it applies an optimization criterion that can directly
      handle the tensor spectral analysis problem, thereby decreasing the computation
      cost compared those traditional tensor-based feature selection algorithms. On the
      other hand, the proposed TRPDA algorithm extracts feature by finding a tensor
      subspace that preserves most of the rank order information of the intra-class
      input samples. Experiments on the three facial databases are performed here to
      determine the effectiveness of the proposed TRPDA algorithm.

PMID- 29028196
TI  - Edge Probability and Pixel Relativity-Based Speckle Reducing Anisotropic
      Diffusion.
AB  - Anisotropic diffusion filters are one of the best choices for speckle reduction
      in the ultrasound images. These filters control the diffusion flux flow using
      local image statistics and provide the desired speckle suppression. However,
      inefficient use of edge characteristics results in either oversmooth image or an
      image containing misinterpreted spurious edges. As a result, the diagnostic
      quality of the images becomes a concern. To alleviate such problems, a novel
      anisotropic diffusion-based speckle reducing filter is proposed in this paper. A
      probability density function of the edges along with pixel relativity information
      is used to control the diffusion flux flow. The probability density function
      helps in removing the spurious edges and the pixel relativity reduces the
      oversmoothing effects. Furthermore, the filtering is performed in superpixel
      domain to reduce the execution time, wherein a minimum of 15% of the total number
      of image pixels can be used. For performance evaluation, 31 frames of three
      synthetic images and 40 real ultrasound images are used. In most of the
      experiments, the proposed filter shows a better performance as compared to the
      state-of-the-art filters in terms of the speckle region's signal-to-noise ratio
      and mean square error. It also shows a comparative performance for figure of
      merit and structural similarity measure index. Furthermore, in the subjective
      evaluation, performed by the expert radiologists, the proposed filter's outputs
      are preferred for the improved contrast and sharpness of the object boundaries.
      Hence, the proposed filtering framework is suitable to reduce the unwanted
      speckle and improve the quality of the ultrasound images.

PMID- 29028197
TI  - Multi-Task Vehicle Detection With Region-of-Interest Voting.
AB  - Vehicle detection is a challenging problem in autonomous driving systems, due to
      its large structural and appearance variations. In this paper, we propose a novel
      vehicle detection scheme based on multi-task deep convolutional neural networks
      (CNNs) and region-of-interest (RoI) voting. In the design of CNN architecture, we
      enrich the supervised information with subcategory, region overlap, bounding-box
      regression, and category of each training RoI as a multi-task learning framework.
      This design allows the CNN model to share visual knowledge among different
      vehicle attributes simultaneously, and thus, detection robustness can be
      effectively improved. In addition, most existing methods consider each RoI
      independently, ignoring the clues from its neighboring RoIs. In our approach, we
      utilize the CNN model to predict the offset direction of each RoI boundary toward
      the corresponding ground truth. Then, each RoI can vote those suitable adjacent
      bounding boxes, which are consistent with this additional information. The voting
      results are combined with the score of each RoI itself to find a more accurate
      location from a large number of candidates. Experimental results on the real
      world computer vision benchmarks KITTI and the PASCAL2007 vehicle data set show
      that our approach achieves superior performance in vehicle detection compared
      with other existing published works.

PMID- 29028198
TI  - A Benchmark Dataset and Saliency-Guided Stacked Autoencoders for Video-Based
      Salient Object Detection.
AB  - Image-based salient object detection (SOD) has been extensively studied in past
      decades. However, video-based SOD is much less explored due to the lack of large
      scale video datasets within which salient objects are unambiguously defined and
      annotated. Toward this end, this paper proposes a video-based SOD dataset that
      consists of 200 videos. In constructing the dataset, we manually annotate all
      objects and regions over 7650 uniformly sampled keyframes and collect the eye
      tracking data of 23 subjects who free-view all videos. From the user data, we
      find that salient objects in a video can be defined as objects that consistently
      pop-out throughout the video, and objects with such attributes can be
      unambiguously annotated by combining manually annotated object/region masks with
      eye-tracking data of multiple subjects. To the best of our knowledge, it is
      currently the largest dataset for video-based salient object detection. Based on
      this dataset, this paper proposes an unsupervised baseline approach for video
      based SOD by using saliency-guided stacked autoencoders. In the proposed
      approach, multiple spatiotemporal saliency cues are first extracted at the pixel,
      superpixel, and object levels. With these saliency cues, stacked autoencoders are
      constructed in an unsupervised manner that automatically infers a saliency score
      for each pixel by progressively encoding the high-dimensional saliency cues
      gathered from the pixel and its spatiotemporal neighbors. In experiments, the
      proposed unsupervised approach is compared with 31 state-of-the-art models on the
      proposed dataset and outperforms 30 of them, including 19 image-based classic
      (unsupervised or non-deep learning) models, six image-based deep learning models,
      and five video-based unsupervised models. Moreover, benchmarking results show
      that the proposed dataset is very challenging and has the potential to boost the
      development of video-based SOD.

PMID- 29028199
TI  - Tensor Factorization for Low-Rank Tensor Completion.
AB  - Recently, a tensor nuclear norm (TNN) based method was proposed to solve the
      tensor completion problem, which has achieved state-of-the-art performance on
      image and video inpainting tasks. However, it requires computing tensor singular
      value decomposition (t-SVD), which costs much computation and thus cannot
      efficiently handle tensor data, due to its natural large scale. Motivated by TNN,
      we propose a novel low-rank tensor factorization method for efficiently solving
      the 3-way tensor completion problem. Our method preserves the low-rank structure
      of a tensor by factorizing it into the product of two tensors of smaller sizes.
      In the optimization process, our method only needs to update two smaller tensors,
      which can be more efficiently conducted than computing t-SVD. Furthermore, we
      prove that the proposed alternating minimization algorithm can converge to a
      Karush-Kuhn-Tucker point. Experimental results on the synthetic data recovery,
      image and video inpainting tasks clearly demonstrate the superior performance and
      efficiency of our developed method over state-of-the-arts including the TNN and
      matricization methods.

PMID- 29028200
TI  - Automatic Optimization of Wayfinding Design.
AB  - Wayfinding signs play an important role in guiding users to navigate in a virtual
      environment and in helping pedestrians to find their ways in a real-world
      architectural site. Conventionally, the wayfinding design of a virtual
      environment is created manually, so as the wayfinding design of a real-world
      architectural site. The many possible navigation scenarios, as well as the
      interplay between signs and human navigation, can make the manual design process
      overwhelming and non-trivial. As a result, creating a wayfinding design for a
      typical layout can take months to several years. In this paper, we introduce the
      Way to Go! approach for automatically generating a wayfinding design for a given
      layout. The designer simply has to specify some navigation scenarios; our
      approach will automatically generate an optimized wayfinding design with signs
      properly placed considering human agents' visibility and possibility of making
      mistakes during a navigation. We demonstrate the effectiveness of our approach in
      generating wayfinding designs for different layouts such as a train station, a
      downtown and a canyon. We evaluate our results by comparing different wayfinding
      designs and show that our optimized wayfinding design can guide pedestrians to
      their destinations effectively and efficiently. Our approach can also help the
      designer visualize the accessibility of a destination from different locations,
      and correct any "blind zone" with additional signs.

PMID- 29028201
TI  - Summed Area Tables for Cube Maps.
AB  - The original Summed Area Table (SAT) structure is designed for handling 2D
      rectangular data. Due to the nature of spherical functions, the SAT structure
      cannot handle cube maps directly. This paper proposes a new SAT structure for
      cube maps and develops the corresponding lookup algorithm. Our formulation starts
      by considering a cube map as part of an auxiliary 3D function defined in a 3D
      rectangular space. We interpret the 2D integration process over the cube map
      surface as a 3D integration over the auxiliary 3D function. One may suggest that
      we can create a 3D SAT for this auxiliary function, and then use the 3D SAT to
      achieve the 3D integration. However, it is not practical to generate or store
      this special 3D SAT directly. This 3D SAT has some nice properties that allow us
      to store it in a storage-friendly data structure, namely Summed Area Cube Map
      (SACM). A SACM can be stored in a standard cube map texture. The lookup algorithm
      of our SACM structure can be implemented efficiently on current graphics
      hardware. In addition, the SACM structure inherits the favorable properties of
      the original SAT structure.

PMID- 29028202
TI  - Feature-based Volumetric Terrain Generation and Decoration.
AB  - Two-dimensional height fields are the most common data structure used for storing
      and rendering of terrain in offline rendering and especially real-time computer
      graphics. By its very nature, a height field cannot store terrain structures with
      multiple vertical layers such as overhanging cliffs, caves, or arches. This
      restriction does not apply to volumetric data structures. However, the workflow
      of manual modelling and editing of volumetric terrain usually is tedious and very
      time-consuming. Therefore, we propose to use three-dimensional curve-based
      primitives to efficiently model prominent, large-scale terrain features. We
      present a technique for volumetric generation of a complete terrain surface from
      the sparse input data by means of diffusion-based algorithms. By combining an
      efficient, feature-based toolset with a volumetric terrain representation, the
      modelling workflow is accelerated and simplified while retaining the full
      artistic freedom of volumetric terrains. Feature Curves also contain material
      information that can be complemented with local details by using per-face texture
      mapping. All stages of our method are GPU-accelerated using compute shaders to
      ensure interactive editing of terrain. Please note that this paper is an extended
      version of our previously published work.

PMID- 29028203
TI  - An Information Theoretical Analysis of Human Insulin-Glucose System Toward the
      Internet of Bio-Nano Things.
AB  - Molecular communication is an important tool to understand biological
      communications with many promising applications in Internet of Bio-Nano Things
      (IoBNT). The insulin-glucose system is of key significance among the major intra
      body nanonetworks, since it fulfills metabolic requirements of the body. The
      study of biological networks from information and communication theoretical (ICT)
      perspective is necessary for their introduction in the IoBNT framework.
      Therefore, the objective of this paper is to provide and analyze for the first
      time in the literature, a simple molecular communication model of the human
      insulin-glucose system from ICT perspective. The data rate, channel capacity, and
      the group propagation delay are analyzed for a two-cell network between a
      pancreatic beta cell and a muscle cell that are connected through a capillary.
      The results point out a correlation between an increase in insulin resistance and
      a decrease in the data rate and channel capacity, an increase in the insulin
      transmission rate, and an increase in the propagation delay. We also propose
      applications for the introduction of the system in the IoBNT framework. Multi
      cell insulin glucose system models may be based on this simple model to help in
      the investigation, diagnosis, and treatment of insulin resistance by means of
      novel IoBNT applications.

PMID- 29028204
TI  - Identifying condition-specific modules by clustering multiple networks.
AB  - Condition-specific modules in multiple networks must be determined to reveal the
      underlying molecular mechanisms of diseases. Current algorithms exhibit
      limitations such as low accuracy and high sensitivity to the number of networks
      because these algorithms discover condition-specific modules in multiple networks
      by separating specificity and modularity of modules. To overcome these
      limitations, we characterize condition-specific module as a group of genes whose
      connectivity is strong in the corresponding network and weak in other networks;
      this strategy can accurately depict the topological structure of condition
      specific modules. We then transform the condition-specific module discovery
      problem into a clustering problem in multiple networks. We develop an efficient
      heuristic algorithm for the Specific Modules in Multiple Networks (SMMN), which
      discovers the condition-specific modules by considering multiple networks. By
      using the artificial networks, we demonstrate that SMMN outperforms state-of-the
      art methods. In breast cancer networks, stage-specific modules discovered by SMMN
      are more discriminative in predicting cancer stages than those obtained by other
      techniques. In pan-cancer networks, cancer-specific modules are more likely to
      associate with survival time of patients, which is critical for cancer therapy.

PMID- 29028205
TI  - MPIGeneNet: Parallel Calculation of Gene Co-Expression Networks on Multicore
      Clusters.
AB  - In this work, we present MPIGeneNet, a parallel tool that applies Pearson's
      correlation and Random Matrix Theory to construct gene co-expression networks. It
      is based on the state-of-the-art sequential tool RMTGeneNet, which provides
      networks with high robustness and sensitivity at the expenses of relatively long
      runtimes for large scale input datasets. MPIGeneNet returns the same results as
      RMTGeneNet but improves the memory management, reduces the I/O cost, and
      accelerates the two most computationally demanding steps of co-expression network
      construction by exploiting the compute capabilities of common multicore CPU
      clusters. Our performance evaluation on two different systems using three typical
      input datasets shows that MPIGeneNet is significantly faster than RMTGeneNet. As
      an example, our tool is up to 175.41 times faster on a cluster with eight nodes,
      each one containing two 12-core Intel Haswell processors. The source code of
      MPIGeneNet, as well as a reference manual, are available at
      https://sourceforge.net/projects/mpigenenet/.

PMID- 29028206
TI  - Grouped Gene Selection of Cancer via Adaptive Sparse Group Lasso Based on
      Conditional Mutual Information.
AB  - This paper deals with the problems of cancer classification and grouped gene
      selection. The weighted gene co-expression network on cancer microarray data is
      employed to identify modules corresponding to biological pathways, based on which
      a strategy of dividing genes into groups is presented. Using the conditional
      mutual information within each divided group, an integrated criterion is proposed
      and the data-driven weights are constructed. They are shown with the ability to
      evaluate both the individual gene significance and the influence to improve
      correlation of all the other pairwise genes in each group. Furthermore, an
      adaptive sparse group lasso is proposed, by which an improved blockwise descent
      algorithm is developed. The results on four cancer data sets demonstrate that the
      proposed adaptive sparse group lasso can effectively perform classification and
      grouped gene selection.

PMID- 29028207
TI  - Clustering-based Compression for Population DNA Sequences.
AB  - Due to the advancement of DNA sequencing techniques, the number of sequenced
      individual genomes has experienced an exponential growth. Thus, effective
      compression of this kind of sequences is highly desired. In this work, we present
      a novel compression algorithm called Reference-based Compression algorithm using
      the concept of Clustering (RCC). The rationale behind RCC is based on the
      observation about the existence of substructures within the population sequences.
      To utilize these substructures, k-means clustering is employed to partition
      sequences into clusters for better compression. A reference sequence is then
      constructed for each cluster so that sequences in that cluster can be compressed
      by referring to this reference sequence. The reference sequence of each cluster
      is also compressed with reference to a sequence which is derived from all the
      reference sequences. Experiments show that RCC can further reduce the compressed
      size by up to 91.0% when compared with state-of-the-art compression approaches.
      There is a compromise between compressed size and processing time. The current
      implementation in Matlab has time complexity in a factor of thousands higher than
      the existing algorithms implemented in C/C++. Further investigation is required
      to improve processing time in future.

PMID- 29028208
TI  - Tunable and Lightweight On-Chip Event Detection for Implantable Bladder Pressure
      Monitoring Devices.
AB  - Lower urinary tract dysfunctions, such as urinary incontinence and overactive
      bladder, are conditions that greatly affect the quality of life for millions of
      individuals worldwide. For those with more complex pathophysiologies, diagnosis
      of these conditions often requires a urodynamics study, providing physicians with
      a snapshot view of bladder mechanics. Recent advancements in implantable bladder
      pressure monitors and advanced data analysis techniques have made diagnosis
      through chronic monitoring a promising prospect. However, implants targeted at
      treatment must remain in the bladder for long periods of time, making minimizing
      power consumption a primary design objective. Currently, much of the typical
      implant's power draw is due to data transmission. Previous work has demonstrated
      an adaptive rate transmission technique to reduce power consumption. However, the
      ultimate reduction in power consumption can only be attained when the device does
      not transmit bladder pressure samples, but rather bladder events. In this paper,
      we present an algorithm and circuit level implementation for on-chip bladder
      pressure data compression and event detection. It is designed to be a complete,
      tunable, and lightweight diagnosis and treatment framework for bladder pressure
      monitoring implants, capable of selectively transmitting compressed bladder
      pressure data with tunable quality, "snapshots" of significant bladder events, or
      simply indicate events occurred for the highest energy efficiency. The design
      aims to minimize area through resource reuse, leading to a total area of 1.75 ,
      and employs advanced VLSI techniques for power reduction. With compression and
      event detection enabled, the design consumes roughly 2.6 nW in TSMC technology.
      With only event detection, this reduces to 2.1 nW, making this approach ideal for
      long-life implantable bladder pressure monitoring devices.

PMID- 29028210
TI  - Extensions to Online Feature Selection Using Bagging and Boosting.
AB  - Feature subset selection can be used to sieve through large volumes of data and
      discover the most informative subset of variables for a particular learning
      problem. Yet, due to memory and other resource constraints (e.g., CPU
      availability), many of the state-of-the-art feature subset selection methods
      cannot be extended to high dimensional data, or data sets with an extremely large
      volume of instances. In this brief, we extend online feature selection (OFS), a
      recently introduced approach that uses partial feature information, by developing
      an ensemble of online linear models to make predictions. The OFS approach employs
      a linear model as the base classifier, which allows the $l_{0}$ -norm of the
      parameter vector to be constrained to perform feature selection leading to sparse
      linear models. We demonstrate that the proposed ensemble model typically yields a
      smaller error rate than any single linear model, while maintaining the same level
      of sparsity and complexity at the time of testing.

PMID- 29028209
TI  - Digital Implementation of the Two-Compartmental Pinsky-Rinzel Pyramidal Neuron
      Model.
AB  - It is believed that brain-like computing system can be achieved by the fusion of
      electronics and neuroscience. In this way, the optimized digital hardware
      implementation of neurons, primary units of nervous system, play a vital role in
      neuromorphic applications. Moreover, one of the main features of pyramidal
      neurons in cortical areas is bursting activities that has a critical role in
      synaptic plasticity. The Pinsky-Rinzel model is a nonlinear two-compartmental
      model for CA3 pyramidal cell that is widely used in neuroscience. In this paper,
      a modified Pinsky-Rinzel pyramidal model is proposed by replacing its complex
      nonlinear equations with piecewise linear approximation. Next, a digital circuit
      is designed for the simplified model to be able to implement on a low-cost
      digital hardware, such as field-programmable gate array (FPGA). Both original and
      proposed models are simulated in MATLAB and next digital circuit simulated in
      Vivado is compared to show that obtained results are in good agreement. Finally,
      the results of physical implementation on FPGA are also illustrated. The
      presented circuit advances preceding designs with regards to the ability to
      replicate essential characteristics of different firing responses including
      bursting and spiking in the compartmental model. This new circuit has various
      applications in neuromorphic engineering, such as developing new neuroinspired
      chips.

PMID- 29028211
TI  - Online Heterogeneous Transfer by Hedge Ensemble of Offline and Online Decisions.
AB  - In this paper, we study the online heterogeneous transfer (OHT) learning problem,
      where the target data of interest arrive in an online manner, while the source
      data and auxiliary co-occurrence data are from offline sources and can be easily
      annotated. OHT is very challenging, since the feature spaces of the source and
      target domains are different. To address this, we propose a novel technique
      called OHT by hedge ensemble by exploiting both offline knowledge and online
      knowledge of different domains. To this end, we build an offline decision
      function based on a heterogeneous similarity that is constructed using labeled
      source data and unlabeled auxiliary co-occurrence data. After that, an online
      decision function is learned from the target data. Last, we employ a hedge
      weighting strategy to combine the offline and online decision functions to
      exploit knowledge from the source and target domains of different feature spaces.
      We also provide a theoretical analysis regarding the mistake bounds of the
      proposed approach. Comprehensive experiments on three real-world data sets
      demonstrate the effectiveness of the proposed technique.

PMID- 29028212
TI  - A Novel Error-Compensation Control for a Class of High-Order Nonlinear Systems
      With Input Delay.
AB  - A novel tracking error-compensation-based adaptive neural control scheme is
      proposed for a class of high-order nonlinear systems with completely unknown
      nonlinearities and input delay. In the tracking errors of existing papers, there
      exist the following difficulties: first, output curve always lags behind the
      desired trajectory, second, some big peak errors cause a decrease in tracking
      precision, and third, a big initial value of the modified tracking error can make
      the closed-loop system unstable. To tackle them, three corresponding error
      compensation terms are constructed, including a prediction and compensation term,
      an auxiliary signal produced by the constructed auxiliary system, and a damping
      term. However, inequality amplification caused by high order will weaken the
      effectiveness of the proposed error-compensation scheme, and the control
      precision will decrease under an assumption that the lower bounds of the unknown
      control coefficients should be exactly known. To overcome aforementioned
      difficulties, in the derivation of the first virtual control law, the radial
      basis function neural network is used to approximate a hybrid term online
      constructed by unknown nonlinearities, a lumped control coefficient achieved by
      state transformation, and the dynamic of the proposed error-compensation terms
      and desired signal. Meanwhile, input delay is coped with a robust compensation
      signal constructed based on a finite integral of the past control values.
      Finally, it is proven that all the closed-loop signals are semiglobally uniformly
      ultimately bounded. Simulation results demonstrate the effectiveness of the
      proposed method.

PMID- 29028213
TI  - Classification of Imbalanced Data by Oversampling in Kernel Space of Support
      Vector Machines.
AB  - Historical data sets for fault stage diagnosis in industrial machines are often
      imbalanced and consist of multiple categories or classes. Learning discriminative
      models from such data sets is challenging due to the lack of representative data
      and the bias of traditional classifiers toward the majority class. Sampling
      methods like synthetic minority oversampling technique (SMOTE) have been
      traditionally used for such problems to artificially balance the data set before
      being trained by a classifier. This paper proposes a weighted kernel-based SMOTE
      (WK-SMOTE) that overcomes the limitation of SMOTE for nonlinear problems by
      oversampling in the feature space of support vector machine (SVM) classifier. The
      proposed oversampling algorithm along with a cost-sensitive SVM formulation is
      shown to improve performance when compared to other baseline methods on multiple
      benchmark imbalanced data sets. In addition, a hierarchical framework is
      developed for multiclass imbalanced problems that have a progressive class order.
      The proposed WK-SMOTE and hierarchical framework are validated on a real-world
      industrial fault detection problem to identify deterioration in insulation of
      high-voltage equipments.

PMID- 29028214
TI  - Dimensionality Reduction in Multiple Ordinal Regression.
AB  - Supervised dimensionality reduction (DR) plays an important role in learning
      systems with high-dimensional data. It projects the data into a low-dimensional
      subspace and keeps the projected data distinguishable in different classes. In
      addition to preserving the discriminant information for binary or multiple
      classes, some real-world applications also require keeping the preference degrees
      of assigning the data to multiple aspects, e.g., to keep the different
      intensities for co-occurring facial expressions or the product ratings in
      different aspects. To address this issue, we propose a novel supervised DR method
      for DR in multiple ordinal regression (DRMOR), whose projected subspace preserves
      all the ordinal information in multiple aspects or labels. We formulate this
      problem as a joint optimization framework to simultaneously perform DR and
      ordinal regression. In contrast to most existing DR methods, which are conducted
      independently of the subsequent classification or ordinal regression, the
      proposed framework fully benefits from both of the procedures. We experimentally
      demonstrate that the proposed DRMOR method (DRMOR-M) well preserves the ordinal
      information from all the aspects or labels in the learned subspace. Moreover,
      DRMOR-M exhibits advantages compared with representative DR or ordinal regression
      algorithms on three standard data sets.

PMID- 29028215
TI  - Spectral Shape Analysis of Human Torsos: Application to the Evaluation of
      Scoliosis Surgery Outcome.
AB  - This paper aims at evaluating the effect of spinal surgery on the torso shape
      appearance of adolescent patients. Current methods that assess the surgical
      outcome on the trunk shape are limited to its global asymmetry or rely on
      unreliable manual measurements. We introduce a novel framework to evaluate pre-
      to postoperative local asymmetry changes using a spectral representation of the
      torso shape, more specifically, the Laplacian spectrum (eigenvalues and
      eigenvectors) of a graph. We conduct a statistical analysis on the eigenvalues to
      efficiently select the spectral space and determine the significant components
      between preop and postop groups. On the selected eigenvectors, we propose a local
      analysis based on the concept of Euler characteristic to detect their local
      maxima and minima, which are then used to compute local left-right (L-R)
      asymmetries of torso shape. On 49 patients with a thoracic spinal deformity, the
      method captures significant pre- to postoperative changes of asymmetry at the
      waist, shoulder blades, shoulders, and breasts. We have evaluated average
      correction rates for L-R asymmetry of the waist height (67%), shoulder-blade
      height (64%) and depth (67%), lateral offset between shoulder and neck (61%), and
      breast height (52%). Spectral torso shape analysis provides a novel approach to
      quantify the surgical correction of the scoliotic trunk from local shape
      asymmetry. The proposed method could help the surgeon to understand the impact of
      different spinal surgery strategies on the postoperative appearance and choose
      the one that should provide better patient's satisfaction.

PMID- 29028216
TI  - Clustering of Morphological Features for Identifying Femur Cavity Subtypes With
      Difficulties of Intramedullary Nail Implantation.
AB  - Intramedullary (IM) nail implantation is currently the standard treatment for
      femoral intertrochanteric fractures. However, individual differences in femur
      cavity bring a challenge in designing well-matched IM nails and cause
      difficulties in IM nail implantation. Therefore, there is an intense need to
      analyze femur cavities to predict difficulties in IM nail implantation to assist
      the design of IM nails. This study proposed a method to automatically identify
      subtypes of femur cavities that exhibit differences in potential difficulties in
      nail implantation by clustering the morphological features of femur models. The
      unsupervised subtype extraction method offers a scientific approach to stratify
      patients for designing and choosing well-matched IM nails. First, the
      quantitative morphological features of 422 femur cavities were extracted from
      computed tomography patient models. Second, 422 femur cavities were clustered
      into three distinct subtypes using a density peak-based k-means clustering method
      to provide a possible solution for the scientific design of IM nails. The
      effectiveness of the identified subtypes was validated by comparing subtype
      differences associated with IM nail implantation and the natural attributes of
      the patient. Quantitative evaluation of the mismatch degree and real clinical
      cases confirmed that the clustering results were clinically effective, with clear
      differences in the subtypes. Therefore, particular IM nails designed from the
      identified subtypes will potentially facilitate IM nail implantation and reduce
      complications. Compared with state-of-the-art methods, we used the largest scale
      dataset and unsupervised clustering to achieve subtype identification of femur
      cavities with clinical significance.

PMID- 29028217
TI  - Efficacy of Guided Spiral Drawing in the Classification of Parkinson's Disease.
AB  - BACKGROUND: Change of handwriting can be an early marker for severity of
      Parkinson's disease but suffers from poor sensitivity and specificity due to
      inter-subject variations. AIM: This study has investigated the group-difference
      in the dynamic features during sketching of spiral between PD and control
      subjects with the aim of developing an accurate method for diagnosing PD
      patients. METHOD: Dynamic handwriting features were computed for 206 specimens
      collected from 62 Subjects (31 Parkinson's and 31 Controls). These were analyzed
      based on the severity of the disease to determine group-difference. Spearman rank
      correlation coefficient was computed to evaluate the strength of association for
      the different features. RESULTS: Maximum area under ROC curve (AUC) using the
      dynamic features during different writing and spiral sketching tasks were in the
      range of 0.67 to 0.79. However, when angular features ($?boldsymbol{?varphi }$
      and ${?boldsymbol{p}_{?boldsymbol{n}}}$) and count of direction inversion during
      sketching of the spiral were used, AUC improved to 0.933. Spearman correlation
      coefficient was highest for phi and ${?boldsymbol{p}_{?boldsymbol{n}}}$.
      CONCLUSION: The angular features and count of direction inversion which can be
      obtained in real-time while sketching the Archimedean guided spiral on a digital
      tablet can be used for differentiating between Parkinson's and healthy cohort.

PMID- 29028218
TI  - Activity Recognition Using Complex Network Analysis.
AB  - In this paper, we perform complex network analysis on a connectivity dataset
      retrieved from a monitoring system in order to classify simple daily activities.
      The monitoring system is composed of a set of wearable sensing modules positioned
      on the subject's body and the connectivity data consists of the correlation
      between each pair of modules. A number of network measures are then computed
      followed by the application of statistical significance and feature selection
      methods. These methods were implemented for the purpose of reducing the total
      number of modules in the monitoring system required to provide accurate activity
      classification. The obtained results show that an overall accuracy of 84.6% for
      activity classification is achieved, using a random forest classifier, and when
      considering a monitoring system composed of only two modules positioned at the
      neck and thigh of the subject's body.

PMID- 29028219
TI  - Data-Driven Finite-Horizon Approximate Optimal Control for Discrete-Time
      Nonlinear Systems Using Iterative HDP Approach.
AB  - This paper presents a data-based finite-horizon optimal control approach for
      discrete-time nonlinear affine systems. The iterative adaptive dynamic
      programming (ADP) is used to approximately solve Hamilton-Jacobi-Bellman equation
      by minimizing the cost function in finite time. The idea is implemented with the
      heuristic dynamic programming (HDP) involved the model network, which makes the
      iterative control at the first step can be obtained without the system function,
      meanwhile the action network is used to obtain the approximate optimal control
      law and the critic network is utilized for approximating the optimal cost
      function. The convergence of the iterative ADP algorithm and the stability of the
      weight estimation errors based on the HDP structure are intensively analyzed.
      Finally, two simulation examples are provided to demonstrate the theoretical
      results and show the performance of the proposed method.

PMID- 29028221
TI  - Quality of Life and Patient-Reported Outcomes Following Proton Radiation Therapy:
      A Systematic Review.
AB  - Background: As costs of cancer care rise, the importance of documenting value in
      oncology increases. Proton beam radiotherapy (PBT) has the potential to reduce
      toxicities in cancer patients, but is relatively expensive and unproven.
      Evaluating quality of life (QOL) and patient-reported outcomes (PROs) is
      essential to establishing PBT's "value" in oncologic therapy. The goal of this
      systematic review was to assess QOL and PROs in patients treated with PBT.
      Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA)-guided systematic searches were conducted. The PubMed search engine was
      the primary data source, along with publications found from references of
      selected articles, and articles known to the authors published through 2017.
      Seventeen original investigations were found to have sufficient focus and
      relevance to be incorporated into the systematic review. Results: Studies of
      skull base (n = 1), brain (n = 1), head/neck (n = 1), lung (n = 1), breast (n =
      2), prostate (n = 8), and pediatric (n = 3) malignancies treated with PBT that
      met eligibility criteria were included. QOL did not deteriorate during PBT for
      skull base and after PBT for brain tumors, respectively. PROs were higher for PBT
      than photon-based radiotherapy for both head/neck and lung cancer. Patient
      reported breast cosmesis was appropriate after PBT and comparable to photon
      modalities. PBT in various settings of prostate cancer displayed an expected post
      therapy decline; one study showed improved PROs (rectal urgency, bowel frequency)
      for PBT, and two others showed PROs/QOL comparable with other modalities.
      Pediatric studies demonstrated improvements in QOL during therapy, with
      additional increases thereafter. Conclusions: Based on limited data, PBT provides
      favorable QOL/PRO profiles for select brain, head/neck, lung, and pediatric
      cancers; measures for prostate and breast cancers were more modest. These results
      have implications for cost-effective cancer care and prudently designed QOL
      evaluation in ongoing trials, which are discussed. Future data could
      substantially change the conclusions of this review.

PMID- 29028223
TI  - Are scientific research outputs aligned with national policy makers' priorities?
      A case study of tuberculosis in Cambodia.
AB  - With funding for tuberculosis (TB) research decreasing, and the high global
      disease burden persisting, there are calls for increased investment in TB
      research. However, justification of such investments is questionable, when
      translation of research outputs into policy and health care improvements remains
      a challenge for TB and other diseases. Using TB in Cambodia as a case study, we
      investigate how evidence needs of national policy makers are addressed by topics
      covered in research publications. We first conducted a systematic review to
      compile all studies on TB in Cambodia published since 2000. We then identified
      priority areas in which evidence for policy and programme planning are required
      from the perspective of key national TB control stakeholders. Finally, results
      from the literature review were analysed in relation to the priority research
      areas for national policy makers to assess overlap and highlight gaps in
      evidence. Priority research areas were: TB-HIV co-infection; childhood TB;
      multidrug resistant TB (MDR-TB); and universal and equitable access to quality
      diagnosis and treatment. On screening 1687 unique papers retrieved from our
      literature search, 253 were eligible publications focusing on TB in Cambodia. Of
      these, only 73 (29%) addressed one of the four priority research areas. Overall,
      30 (11%), five (2%), seven (2%) and 37 (14%) studies reported findings relevant
      to TB-HIV, childhood TB, MDR-TB and access to quality diagnosis and treatment
      respectively. Our analysis shows that a small proportion of the research outputs
      in Cambodia address priority areas for informing policy and programme planning.
      This case study illustrates that there is substantial room for improvement in
      alignment between research outputs and evidence gaps that national policy makers
      would like to see addressed; better coordination between researchers, funders and
      policy makers' on identifying priority research topics may increase the relevance
      of research findings to health policies and programmes.

PMID- 29028222
TI  - Role of RBP2-Induced ER and IGF1R-ErbB Signaling in Tamoxifen Resistance in
      Breast Cancer.
AB  - Background: Despite the benefit of endocrine therapy, acquired resistance during
      or after treatment still remains a major challenge in estrogen receptor (ER)
      positive breast cancer. We investigated the potential role of histone demethylase
      retinoblastoma-binding protein 2 (RBP2) in endocrine therapy resistance of breast
      cancer. Methods: Survival of breast cancer patients according to RBP2 expression
      was analyzed in three different breast cancer cohorts including METABRIC (n =
      1980) and KM plotter (n = 1764). RBP2-mediated tamoxifen resistance was confirmed
      by invitro sulforhodamine B (SRB) colorimetric, colony-forming assays, and invivo
      xenograft models (n = 8 per group). RNA-seq analysis and receptor tyrosine kinase
      assay were performed to identify the tamoxifen resistance mechanism by RBP2. All
      statistical tests were two-sided. Results: RBP2 was associated with poor
      prognosis to tamoxifen therapy in ER-positive breast cancer (P = .04 in HYU
      cohort, P = .02 in KM plotter, P = .007 in METABRIC, log-rank test). Furthermore,
      RBP2 expression was elevated in patients with tamoxifen-resistant breast cancer
      (P = .04, chi-square test). Knockdown of RBP2 conferred tamoxifen sensitivity,
      whereas overexpression of RBP2 induced tamoxifen resistance invitro and invivo
      (MCF7 xenograft: tamoxifen-treated control, mean [SD] tumor volume = 70.8 [27.9]
      mm3, vs tamoxifen-treated RBP2, mean [SD] tumor volume = 387.9 [85.1] mm3, P <
      .001). Mechanistically, RBP2 cooperated with ER co-activators and corepressors
      and regulated several tamoxifen resistance-associated genes, including NRIP1,
      CCND1, and IGFBP4 and IGFBP5. Furthermore, epigenetic silencing of IGFBP4/5 by
      RBP2-ER-NRIP1-HDAC1 complex led to insulin-like growth factor-1 receptor (IGF1R)
      activation. RBP2 also increased IGF1R-ErbB crosstalk and subsequent PI3K-AKT
      activation via demethylase activity-independent ErbB protein stabilization.
      Combinational treatment with tamoxifen and PI3K inhibitor could overcome RBP2
      mediated tamoxifen resistance (RBP2-overexpressing cells: % cell viability [SD],
      tamoxifen = 89.0 [3.8]%, vs tamoxifen with BKM120 = 41.3 [5.6]%, P < .001).
      Conclusions: RBP2 activates ER-IGF1R-ErbB signaling cascade in multiple ways to
      induce tamoxifen resistance, suggesting that RBP2 is a potential therapeutic
      target for ER-driven cancer.

PMID- 29028220
TI  - Pediatric brain repair from endogenous neural stem cells of the subventricular
      zone.
AB  - There is great interest in the regenerative potential of the neural stem cells
      and progenitors that populate the germinal zones of the immature brain. Studies
      using animal models of pediatric brain injuries have provided a clearer
      understanding of the responses of these progenitors to injury. In this review, we
      have compared and contrasted the responses of the endogenous neural stem cells
      and progenitors of the subventricular zone in animal models of neonatal cerebral
      hypoxia-ischemia, neonatal stroke, congenital cardiac disease, and pediatric
      traumatic brain injury. We have reviewed the dynamic shifts that occur within
      this germinal zone with injury as well as changes in known signaling molecules
      that affect these progenitors. Importantly, we have summarized data on the extent
      to which cell replacement occurs in response to each of these injuries,
      opportunities available, and obstacles that will need to be overcome to improve
      neurological outcomes in survivors.

PMID- 29028224
TI  - Are global tuberculosis control targets overlooking an essential indicator?
      Prolonged delays to diagnosis despite high case detection rates in Yunnan, China.
AB  - Delay in treating active tuberculosis (TB) impedes disease control by allowing
      ongoing transmission, and may explain the unexpectedly modest declines in global
      TB incidence. Even though China has achieved TB control targets under the global
      Directly Observed Treatment, Short course (DOTS) strategy, TB prevalence in
      western provinces, including Yunnan, is not decreasing. This cross-sectional
      study investigates whether prolonged delay in identifying and correctly treating
      TB patients, which is not routinely monitored, persists even when there is a well
      functioning TB control programme and global targets are being met. Records of
      adult smear-positive pulmonary TB patients diagnosed with between 2006 and 2013
      were extracted from the Yunnan Centre for Disease Control electronic database,
      which contains information on the entire population of TB patients managed across
      129 diagnostic centres. Delay was investigated at three stages: delay to DOTS
      facility (period between symptom onset and first visit to at a CDC unit providing
      standardized treatment); delay to TB confirmation (period between reaching a CDC
      unit and confirmation of smear-positive TB) and delay to treatment (period
      between confirmation of TB and initiation of treatment). Data from 76 486
      patients was analysed. Delay to reaching a DOTS facility was by far the largest
      contributor to total delay to treatment initiation. The median delay to reaching
      a DOTS facility, to TB confirmation and to treatment was 57 days (IQR 25-112), 2
      days (IQR 1-6) and 1 day (IQR 0-1) respectively. Prolonged delays to reaching a
      facility providing standardized TB care occurred in a substantial subset of the
      population despite all TB control targets being met; overall, 32% (24 676) of
      patients experienced a delay of more than 90 days to reaching a DOTS facility.
      Policies that focus on reducing delays in accessing appropriate health services,
      rather than only on increasing overall case-detection rates, may result in
      greater progress towards reducing TB incidence.

PMID- 29028225
TI  - Optimising routine surveillance systems for informing tuberculosis control
      policies in China.

PMID- 29028226
TI  - Large funding inflows, limited local capacity and emerging disease control
      priorities: a situational assessment of tuberculosis control in Myanmar.
AB  - There are numerous challenges in planning and implementing effective disease
      control programmes in Myanmar, which is undergoing internal political and
      economic transformations whilst experiencing massive inflows of external funding.
      The objective of our study-involving key informant discussions, participant
      observations and linked literature reviews-was to analyse how tuberculosis (TB)
      control strategies in Myanmar are influenced by the broader political, economic,
      epidemiological and health systems context using the Systemic Rapid Assessment
      conceptual and analytical framework. Our findings indicate that the substantial
      influx of donor funding, in the order of one billion dollars over a 5-year
      period, may be too rapid for the country's infrastructure to effectively utilize.
      TB control strategies thus far have tended to favour medical or technological
      approaches rather than infrastructure development, and appear to be driven more
      by perceived urgency to 'do something' rather informed by evidence of cost
      effectiveness and sustainable long-term impact. Progress has been made towards
      ambitious targets for scaling up treatment of drug-resistant TB, although there
      are concerns about ensuring quality of care. We also find substantial disparities
      in health and funding allocation between regions and ethnic groups, which are
      related to the political context and health system infrastructure. Our
      situational assessment of emerging TB control strategies in this transitioning
      health system indicates that large investments by international donors may be
      pushing Myanmar to scale up TB and drug-resistant TB services too quickly,
      without due consideration given to the health system (service delivery
      infrastructure, human resource capacity, quality of care, equity) and
      epidemiological (evidence of effectiveness of interventions, prevention of new
      cases) context.

PMID- 29028228
TI  - Preventing emergence of drug resistant tuberculosis in Myanmar's transitioning
      health system.
AB  - Multidrug-resistant tuberculosis (MDR-TB) is a particular threat to the
      populations of resource-limited countries. Although inadequate treatment of TB
      has been identified as a major underlying cause of drug resistance, essential
      information to inform changes in health service delivery and policy is missing.
      We investigate factors that may be driving the emergence of MDR-TB in Myanmar, a
      country where investment and health system reforms are ongoing to address the
      unexplained, high occurrence of MDR-TB. We conducted a multi-centre,
      retrospective case-control study in 10 townships across Yangon. Cases were 202
      GeneXpert-confirmed MDR-TB patients with a history of prior first-line treatment
      for TB. Controls were 404 previously untreated smear-microscopy confirmed TB
      patients who had no evidence of resistance to anti-TB drugs. Information on
      patient and health service factors was collected through face-to-face patient
      interviews and hospital record reviews. Multivariable logistic regression
      analysis indicated that the following TB patient groups are at higher risk of
      developing MDR-TB after initial TB treatment: those who have diabetes (aOR 2.10;
      95% CI 1.17-3.76), those who missed taking drugs during the initial treatment
      more than once weekly (aOR 2.35; 95% CI 1.18-4.65) and those with a higher
      socioeconomic (aOR 1.99; 95% CI 1.09-3.63) or educational status (aOR 1.78; 95%
      CI1.01-3.13). Coinciding with a surge in funding to improve health in Myanmar,
      this study identifies practices of patients and healthcare organizations that can
      be addressed, and high-risk TB patient groups that can be prioritized for
      treatment support. Specifically, the study shows that TB patients who experience
      frequent, short interruptions in treatment and those with diabetes may require
      enhanced treatment support and monitoring by health services in order to prevent
      further generation of drug resistance.

PMID- 29028229
TI  - Tuberculosis control in South East Asia: vignettes from China, Cambodia and
      Myanmar.

PMID- 29028227
TI  - A strong TB programme embedded in a developing primary healthcare system is a
      lose-lose situation: insights from patient and community perspectives in
      Cambodia.
AB  - As exemplified by the situation in Cambodia, disease specific (vertical) health
      programmes are often favoured when the health system is fragile. The potential of
      such an approach to impede strengthening of primary healthcare services has been
      studied from a health systems perspective in terms of access and quality of care.
      In this bottom-up, qualitative study we investigate patient and community member
      experiences of health services when a strong tuberculosis (TB) programme is
      embedded into a relatively underutilized primary healthcare system. We conducted
      six gender-stratified community focus group discussions (n = 49) and seven mixed
      gender focus group discussions with TB patients (n = 45) in three provinces
      located in urban, peri-urban and rural areas of Cambodia. Our analysis of health
      seeking behaviour and experiences for TB and TB-like illness indicates that
      building a strong vertical TB control programme has had numerous benefits,
      including awareness of typical symptoms and need to seek care early; confidence
      in free TB services at public facilities; and willingness to complete treatment.
      However, there was a clear dichotomy in experiences and behaviour with respect to
      care-seeking for less severe illness at primary health services, which were
      generally avoided owing to access barriers and perceived poor quality. The
      tendency to delay seeking health care until the development of severe symptoms
      clearly indicative of TB is a major barrier to early diagnosis and treatment of
      TB. Our study indicates that an imbalance in the strength of vertical and primary
      health services could be a lose-lose situation as this impedes improvements in
      health system functioning and constrains progress of vertical disease control
      programmes.

PMID- 29028230
TI  - Fine-scale spatial patterns in microbial community composition in an acid mine
      drainage.
AB  - Microbial community composition is essential for aquatic ecosystem functions and
      has been explored across diverse environments and various spatial scales.
      However, documented patterns are often based on samples from
      spatially/geographically separated locations or sites. Here, we define sampling
      volume as spatial scale and examine (by Illumina 16S rRNA sequencing) microbial
      community composition over a scale of 1 mL to 10 L in an acid mine drainage. beta
      Diversity analysis revealed that all samples grouped very tightly according to
      spatial scales and variations between every two scales were significant. Notably,
      mean beta-diversity within each group was negatively correlated with spatial
      scales, indicating patchy microbial distribution. Partition of beta-diversity
      further revealed that it was the relative abundances of some microbial taxa that
      largely changed among spatial scales. Phylogenetic analysis showed that microbial
      lineages were not randomly distributed, but displayed a tendency of more
      phylogenetically clustering at smaller spatial scales. Thus, we documented fine
      scale spatial patterns in microbial community composition within a continuous
      aquatic environment, which may have practical implications for adequate sampling
      of aquatic systems in future studies.

PMID- 29028231
TI  - Policy, politics and public health.
AB  - If public health is the field that diagnoses and strives to cure social ills,
      then understanding political causes and cures for health problems should be an
      intrinsic part of the field. In this article, we argue that there is no support
      for the simple and common, implicit model of politics in which scientific
      evidence plus political will produces healthy policies. Efforts to improve the
      translation of evidence into policy such as knowledge transfer work only under
      certain circumstances. These circumstances are frequently political, and to be
      understood through systematic inquiry into basic features of the political
      economy such as institutions, partisanship and the organization of labour
      markets.

PMID- 29028232
TI  - Towards an overarching European health information system.
AB  - A European health information system (HIS) supports mutual learning between
      member states through international comparisons. In addition, it informs
      international policy agendas. Collaboration between the major stakeholders, most
      importantly the World Health Organization Regional Office for Europe (WHO-Euro),
      the European Commission and OECD, is important for member states, as this will
      contribute to better and more efficiently produced health intelligence. This
      paper focuses on this 'supra-international' collaboration. Although progress has
      been made, most notably in relation to joint data collections on monetary and non
      monetary healthcare statistics, there is still room for improvement, both in
      relation to the harmonization of indicators and their underlying data
      collections, and the better coordination of reporting and research and
      development work. The working environment is complex, and differences between the
      (scope of the) health information activities of the three international
      organizations must be accepted. Yet there is enough common ground to build on. In
      addition, important barriers hampering further progress are the current semantic
      confusion about what constitutes a(n international) HIS, and inadequate
      coordination of national positions across various technical and political
      platforms of the international organizations. A pragmatic, bottom-up approach,
      instead of technically and strategically complex and comprehensive solutions,
      seems the best way forward. The current momentum created by EU-level developments
      and networks like the European Health Information Initiative of WHO-Euro provide
      an opportunity for taking the overarching European HIS to a next level.

PMID- 29028233
TI  - Ethics in public health: call for shared moral public health literacy.
AB  - Public Health (PH) in Europe has become much more vocal about its moral
      understandings since 1992. The rising awareness that PH issues were inseparable
      from issues of human rights and social justice almost self-evidently directed the
      agenda of EUPHA and the European Public Health (EPH)-conferences. Problems of
      cultural and behavioural change, and environmental issues on a global scale were
      also added. The Section Ethics in PH invited the EPH community to join in 'arm
      chair thinking': coming together at conferences not only to share the 'how' and
      'what' of PH research, practices and policies but also the 'why'. Time has been
      reserved to genuinely discuss what moral values are at stake in the work of PH
      and to actively develop a moral language and framework for PH Ethics. The
      challenge for the next decades is to find ways to involve the general public in
      the cultivation of a shared moral PH literacy.

PMID- 29028234
TI  - What role can civil society organizations have in European health policy?
AB  - Over the years, the main European institutions active in health [European Union,
      and the Regional Office for Europe of the World Health Organization (WHO)] have
      played active roles in policy for public health in Europe. Yet, more recent
      developments have called into question the place of public health on the European
      political agenda. In this article, we reflect on how European health policy is
      set and what the role of civil society organizations (CSOs) can or should be, by
      showcasing two European associations as examples of how to influence European
      health policy development and implementation.

PMID- 29028235
TI  - How to include public health practice and practitioners in a European Network.
AB  - There is a wide range of different Public Health (PH) activities and programs
      running in Europe. Besides the richness of national traditions, differences exist
      in numbers of programs, methods adopted, types of engaged professionals,
      available resources (including public investments), awareness to the problem and
      finally in health indicators among and within countries. Promoting networks of PH
      practices and practitioners strengthens the possibility to share knowledge across
      organizational, sectorial and geographic boundaries, promotes adaptation and
      local implementation, fosters innovation in the form of knowledge creation by
      developing more efficient new services and by sharing effective practices within
      and between organizations and sectors. Nevertheless, strengthening existing
      networks and promoting new ones requires coordinated efforts based on complex
      adaptive systems and network science rules, along with the engagement of local,
      national and European health authorities. Given these premises, networking
      promotion and development is a promising way to improve health and wealth to
      European citizens and communities.

PMID- 29028236
TI  - EUPHA, a timely adventure.

PMID- 29028237
TI  - The epidemiological transition in Eastern and Western Europe: a historic natural
      experiment.
AB  - Background: The continent of Europe has experienced remarkable changes in the
      past 25 years, providing scope for natural experiments that offer insight into
      the complex determinants of health. Methods: We analysed trends in life
      expectancy at birth in three parts of Europe, those countries that were members
      of the European Union (EU) prior to 2004, countries that joined the European
      Union since then, and the twelve countries that emerged from the Soviet Union to
      form the Commonwealth of Independent States (CIS). The contribution of deaths at
      different ages to these changes was assessed using Arriaga's method of
      decomposing changes in life expectancy. Results: Europe remains divided
      geographically, with an East-West gradient. The former Soviet countries
      experienced a marked initial decline in life expectancy and have only recovered
      after 2005. However, the situation for those of working ages is little better
      than in 1990. The pre-2004 EU has seen substantial gains throughout the past 25
      years, although there is some evidence that this may be slowing, or even
      reversing, at older ages. The countries joining the EU in 2004 subsequently began
      to see some improvements in the early 1990s, but have experienced larger gains
      since 2000. Conclusions: Europe offers a valuable natural laboratory for
      understanding the impact of political, economic, and social changes on health.
      While the historic divisions of Europe are still visible, there is also evidence
      that individual countries are doing better or worse than their neighbours,
      providing many lessons that can be learned from.

PMID- 29028238
TI  - Demographic trends and public health in Europe.
AB  - Demographic trends in Europe are currently being shaped by an ageing population,
      falling fertility rates and diverse migration flows. Fertility rates are lowest
      in Eastern and Southern Europe with Eastern Europe also experiencing the lowest
      net migration and an exodus of its working population. All regions in Europe are
      experiencing aging of their population with some countries having the added
      burden of high rates of unemployment among the working age population. The impact
      of these demographic changes on the current and future public health of the
      country depends on how countries have been preparing and adapting to demographic
      changes over the past years. Changes in age structure and ethnic composition will
      put further strain on health care and welfare systems and requires careful
      planning. A multi-faceted approach which goes beyond the health care system is
      required and countries need to look beyond their borders in search as to how
      countries are tackling these important issues. As Europe ages the concept of
      healthy aging should become an increasing priority focus for European Public
      Health.

PMID- 29028239
TI  - Nordic paradox, Southern miracle, Eastern disaster: persistence of inequalities
      in mortality in Europe.
AB  - The persistence of socioeconomic inequalities in health, despite all that has
      been done to reduce social and economic inequalities in many European countries,
      is one of the great disappointments of public health. In this paper, I summarize
      the results of a series of studies into the explanation of variations and trends
      in inequalities in mortality in three European regions: the Nordic countries with
      their puzzlingly large inequalities in mortality, Southern European countries
      with their miraculously small inequalities in mortality and Central & Eastern
      European countries in which inequalities in mortality have disastrously exploded
      since the early 1990 s. The results of these studies show that inequalities in
      mortality are remarkably variable and dynamic, which suggests that it may be
      possible to reduce them if we exploit the entry-points for policy that these
      studies have also identified, such as poverty, smoking, excessive alcohol
      consumption and lack of access to health care. At the same time, another lesson
      is that health inequalities are influenced in sometimes unexpected ways by
      factors that are not under our control, and that we cannot expect to eliminate
      these health inequalities soon.

PMID- 29028240
TI  - Tobacco still a major killer-will we achieve the end game?
AB  - The game of tobacco use began in Europe in 1560 when the first tobacco seeds were
      sent from Lisbon to the king of France, by Jean Nicot. From kings' and nobles'
      exclusive use, it gradually and progressively became popular among the public, as
      a new player. Eighty-eight years ago (1929), Fritz Linkint, an extraordinary
      researcher in Germany, while reviewing existing evidence regarding a wide range
      of cancers potentially caused by smoking, indicated that smoking was a cause of
      respiratory disease. Despite the overwhelming accumulated evidence of the
      negative effects of nicotine intake, the prevalence of tobacco use is not
      expected to decline in the near future. What have we missed thus far in the game
      that claims more than seven million deaths annually worldwide? Although tobacco
      use is recognized as a major health problem, the persistent habit creates a
      dissonance between public health initiatives to reduce tobacco consumption and
      the choices citizens are making. To understand this dissonance, consideration
      first must be given to the social meaning attributed to smoking. Second, the
      political dissonance between health imperatives and social agendas is discussed
      with regard to relevant theory. Third, health promotion strategies can make a
      strong contribution to win the game from a negentropic perspective, that is to
      say, a public health vision that is structured towards an overarching goal.

PMID- 29028241
TI  - 'Du bist was du isst': challenges in European nutrition policy.
AB  - Food cultures have developed in communities as according to the produce of local
      farms in the vicinity. The industrial revolution resulted in large cities and
      towns becoming reliant on farm produce from the neighbouring countryside; this
      stimulated development of farming, which itself became industrialized. However,
      although local diets in Europe differed markedly, the 'healthiness' of all diets
      was unquestioned until recently. Early in the 20th century, academic departments
      studying nutrition were established, but it is only since the 1980s that much
      interest in the 'healthiness' of our food began to be of concern outwith
      academia. At about this time it was becoming clear that existing patterns of
      farming and food production were having negative effects on the environment.
      Since the 1990s, environmental, farming and nutritional sciences have each
      progressed, but in parallel, and there has been all too little effort to unite
      them. However, it is clear that, in general, production of foods associated with
      'unhealthy' nutrition is also the most damaging from an environmental
      viewpoint.This article summarizes the evidence on current European diets,
      analyses costs and benefits in transitioning to healthy and sustainable diets,
      identifies sustainable dietary guidelines as the way forward and discusses the
      role of public health in achieving dietary reform in the interests of improved
      nutrition and environmental protection.

PMID- 29028242
TI  - Public mental health.
AB  - Public mental health (PMH) is a major challenge for public health research and
      practice. This article is organized in six parts. First, we will highlight the
      significance of PMH; second, we will define mental health and mental disorders;
      third, we identify and describe determinants of mental health and mental
      disorders on which we worked in the past 10 years since the establishment of the
      PMH section such as social determinants and violence. Fourth, we will describe
      the development of the EUPHA PMH section and provide details on vulnerable groups
      in the field of PMH, on violence as a main determinant and on suicide as an
      outcome which affects all countries in the European region. Fifth, we describe
      policy and practice implications of the development of PMH and highlight the
      European dimension of PMH. We will conclude this article by providing an outlook
      on potential further development of PMH as regards research and policy and
      practice. Finally, we hope that the EUPHA PMH section will contribute to public
      health in the next 25 years and we can contribute to improvement of PMH in
      Europe.

PMID- 29028243
TI  - New challenges of public health: bringing the future of personalised healthcare
      into focus.
AB  - The greater personalization of healthcare represents a driver of innovation for
      research, and for the healthcare systems and industries as a whole. Still policy
      makers, healthcare professionals, citizens and private companies need to take
      some steps to realize the potential for such a radical shift. In this paper, we
      illustrate the challenges, the benefits and consequences that might accompany the
      implementation of personalized healthcare, and the steps that policy-makers and
      practitioners would need to take to realise its potential. Six main prerequisites
      for radical change in healthcare are presented, that include achieving better
      genetic literacy for professionals and for the public; engaging citizen in the
      discourse; improved governance, consent and trust in healthcare; feeding and
      harnessing the data-knowledge cycle for better health; adopting and adapting the
      Health Technology Assessment framework for the evaluation of the new
      technologies; and retaining humanity and community in health and care. Some of
      these concepts originate from a discussion on the future of health and
      healthcare, looking at least 15-20 years into the future, that we had at the end
      of 2016 at Ickworth with an international group of experts, under the aegis of
      the PHG Foundation.

PMID- 29028244
TI  - Celebrating EUPHA's 25th anniversary.

PMID- 29028245
TI  - Austerity and health: the impact in the UK and Europe.
AB  - Austerity measures-reducing social spending and increasing taxation-hurts
      deprived groups the most. Less is known about the impact on health. In this short
      review, we evaluate the evidence of austerity's impact on health, through two
      main mechanisms: a 'social risk effect' of increasing unemployment, poverty,
      homelessness and other socio-economic risk factors (indirect), and a 'healthcare
      effect' through cuts to healthcare services, as well as reductions in health
      coverage and restricting access to care (direct). We distinguish those impacts of
      economic crises from those of austerity as a response to it. Where possible, data
      from across Europe will be drawn upon, as well as more extensive analysis of the
      UK's austerity measures performed by the authors of this review.

PMID- 29028246
TI  - Validation of Lower Tier Exposure Tools Used for REACH: Comparison of Tools
      Estimates With Available Exposure Measurements.
AB  - Background: Tier 1 exposure tools recommended for use under REACH are designed to
      easily identify situations that may pose a risk to health through conservative
      exposure predictions. However, no comprehensive evaluation of the performance of
      the lower tier tools has previously been carried out. The ETEAM project aimed to
      evaluate several lower tier exposure tools (ECETOC TRA, MEASE, and EMKG-EXPO
      TOOL) as well as one higher tier tool (STOFFENMANAGER(r)). This paper describes
      the results of the external validation of tool estimates using measurement data.
      Methods: Measurement data were collected from a range of providers, both in
      Europe and United States, together with contextual information. Individual
      measurement and aggregated measurement data were obtained. The contextual
      information was coded into the tools to obtain exposure estimates. Results were
      expressed as percentage of measurements exceeding the tool estimates and
      presented by exposure category (non-volatile liquid, volatile liquid, metal
      abrasion, metal processing, and powder handling). We also explored tool
      performance for different process activities as well as different scenario
      conditions and exposure levels. Results: In total, results from nearly 4000
      measurements were obtained, with the majority for the use of volatile liquids and
      powder handling. The comparisons of measurement results with tool estimates
      suggest that the tools are generally conservative. However, the tools were more
      conservative when estimating exposure from powder handling compared to volatile
      liquids and other exposure categories. In addition, results suggested that tool
      performance varies between process activities and scenario conditions. For
      example, tools were less conservative when estimating exposure during activities
      involving tabletting, compression, extrusion, pelletisation, granulation (common
      process activity PROC14) and transfer of substance or mixture (charging and
      discharging) at non-dedicated facilities (PROC8a; powder handling only). With the
      exception of STOFFENMANAGER(r) (for estimating exposure during powder handling),
      the tools were less conservative for scenarios with lower estimated exposure
      levels. Conclusions: This is the most comprehensive evaluation of the performance
      of REACH exposure tools carried out to date. The results show that, although
      generally conservative, the tools may not always achieve the performance
      specified in the REACH guidance, i.e. using the 75th or 90th percentile of the
      exposure distribution for the risk characterisation. Ongoing development,
      adjustment, and recalibration of the tools with new measurement data are
      essential to ensure adequate characterisation and control of worker exposure to
      hazardous substances.

PMID- 29028247
TI  - Atopy as a Modifier of the Relationships Between Endotoxin Exposure and Symptoms
      Among Laboratory Animal Workers.
AB  - Background: Exposure to endotoxin is known to trigger airway inflammation and
      symptoms, and atopy may modify the relationship between endotoxin exposure and
      symptom development. Objective: To test the a priori hypothesis that atopic
      status modifies the relationship between endotoxin exposure and respiratory
      symptom development. Methods: A prospective study of laboratory workers at The
      Jackson Laboratories was conducted. Allergy skin testing was performed and
      population demographic and clinical information was obtained at baseline.
      Personal exposure assessments for airborne endotoxin and surveys of self-reported
      symptoms were performed every 6 months. Cox proportional hazards models were used
      to examine the relationship between endotoxin exposure and development of mouse
      associated symptoms and multivariate regression was used to test for interaction.
      Results: Overall, 16 (9%) of 174 worker-participants developed mouse-associated
      rhinoconjunctivitis symptoms by 24 months and 8 (5%) developed mouse-associated
      lower respiratory symptoms by 24 months. Among workers with endotoxin exposure
      above the median (>=2.4 EU m-3), 5 (6% of 80) atopics reported mouse-associated
      rhinoconjunctivitis symptoms at 24 months as compared to 3 (3% of 94) non
      atopics. Among workers below the median endotoxin exposure (<2.4 EU m-3), 1 (1%
      of 80) atopic reported mouse-associated rhinoconjunctivitis symptoms at 24 months
      as compared to 7 (7% of 94) non-atopics. For the combination of symptoms, the
      adjusted hazard ratio was 6.8 (95% confidence interval: 0.7-67.2) for atopics and
      0.07 (95% confidence interval: 0.01-0.5) for non-atopics. Conclusion: In this
      occupational cohort, atopic workers may be more susceptible to, and non-atopic
      workers protected from, endotoxin-associated upper and lower respiratory
      symptoms.

PMID- 29028248
TI  - Blue-Light Hazard From Gas Metal Arc Welding of Aluminum Alloys.
AB  - Objectives: The objective was to quantify the blue-light hazard from gas metal
      arc welding (GMAW) of aluminum alloys. The exposure level is expected to depend
      on the welding conditions. Therefore, it is important to identify the blue-light
      hazard under various welding conditions. Methods: We experimentally conducted
      GMAW of aluminum alloys under various welding conditions and measured the
      spectral radiance of the arcs. The effective blue-light radiance, which the
      American Conference of Governmental Industrial Hygienists has defined to quantify
      the exposure level of blue light, was calculated from the measured spectral
      radiance. The maximum acceptable exposure duration per 10000 s for this effective
      blue-light radiance was calculated. Results: The effective blue-light radiance
      measured in this study was in the range of 2.9-20.0 W cm-2.sr. The corresponding
      maximum acceptable exposure duration per 10000 s was only 5.0-34 s, so it is
      hazardous to view the welding arc. The effective blue-light radiance was higher
      at higher welding currents than at lower welding currents, when pulsed welding
      currents were used rather than steady welding currents, and when magnesium was
      included in the welding materials. Conclusions: It is very hazardous to view the
      arcs in GMAW of aluminum alloys. Welders and their helpers should use appropriate
      eye protection in arc-welding operations. They should also avoid direct light
      exposure when starting an arc-welding operation.

PMID- 29028249
TI  - A Method to Quantitatively Assess Dermal Exposure to Volatile Organic Compounds.
AB  - Assessing dermal exposure of workers to noxious chemicals becomes increasingly
      important in industrial settings. Among various chemicals, volatile organic
      compounds (VOCs) are widely used in industrialized countries, but still there are
      no validated methodologies able to accurately quantify skin exposure. In this
      study, we developed a sensitive methodology based on activated charcoal cloth
      (ACC) to quantitatively assess skin exposure to 181 VOCs. The majority of the
      VOCs (156) showed a constant desorption efficiency (DE) of ~100% over the studied
      concentration range. Seven VOCs showed a concentration dependency for the DEs,
      which we described by a Dubinin-Raduskevich desorption isotherm. For 18
      compounds, the DEs were situated below 80% but showed to be constant over the
      concentration range. All tested VOCs showed a good storage stability on ACC,
      especially at -80 degrees C storage. Only for n-pentane there was a decrease of
      ~40% when it was stored for a month. In a controlled environment test, ACC has
      shown to reflect well the increasing concentrations of VOCs in the air with a
      high linearity (R2 >= 0.812, except for gamma-butyrolactone where R2 = 0.570). In
      this study, we show that ACC is a suitable sampling material for quantitatively
      assessing dermal exposure to 181 VOCs in terms of sensitivity and DE. This method
      will allow more studies that are detailed on dermal exposure, which will lead to
      a better assessment of skin exposure in occupational settings.

PMID- 29028250
TI  - Comprehensive Biological Monitoring to Assess Isocyanates and Solvents Exposure
      in the NSW Australia Motor Vehicle Repair Industry.
AB  - Urethane products that contain isocyanates are extensively used in the motor
      vehicle repair (MVR) industry and other industries such as furniture and cabinet
      making as two-pack spray paints, clears, and adhesives. Attention has recently
      been refocussed on isocyanate-containing chemicals, particularly in paints. The
      spray painters in the MVR industry had a propensity to develop industrial asthma
      at a rate 80 times higher than the general public, which was previously reported
      in the UK. To track workers exposure to isocyanates, urine samples were collected
      from 196 spray painters who worked mainly in 78 MVR shops across 54 New South
      Wales (NSW) towns and suburbs. The biological monitoring also covered exposure
      testing to a wide variety of solvents including aromatic hydrocarbons, ketones,
      and alcohols. The main finding of the study was that 2.6% of the spray painters
      surveyed in the MVR industry in NSW that handled isocyanate-containing paints
      showed exposure to isocyanates; with 1.0% being moderately exposed, which is more
      than twice the current UK's Health and Safety Executive (HSE) Biological
      Monitoring Guidance Value (BMGV) of 1 umol mol-1 creatinine. Potential exposures
      to toluene (a solvent often found in paint thinners) was monitored via hippuric
      acid (HA) urine levels and showed 2.6% of the spray painters surveyed to be over
      the US' American Conference of Government Industrial Hygienists (ACGIH)
      Biological Exposure Index (BEI) of 1010 mmol/mole creatinine for HA. The other
      solvents or their metabolites were all below their respective BEI; these
      comprised benzene, xylene, ethyl benzene, methyl ethyl ketone, acetone, methanol,
      and ethanol. These findings indicate that isocyanates and certain solvents
      exposure were occurring in the NSW Australia vehicle repair industry, albeit at
      lower levels than previous occupational biological monitoring studies that showed
      higher exposure levels, particularly for isocyanates. One reason for this could
      be the increasing use of water-based paints in the industry, resulting in lower
      than expected isocyanate and solvent metabolite levels detected in this more
      recent study. Further, the completion of sample context form, along with spot
      urine collection in relation to the isocyanate exposure monitoring work details
      will provide crucial information to interpret the biological analysis results.
      The development of new biomarkers of isocyanate oligomer-derived triamines should
      be incorporated in the assessment of isocyanate exposure in the MVR industry to
      provide a more complete picture of isocyanate exposure.

PMID- 29028251
TI  - Monitoring Surface Contamination by Antineoplastic Drugs in Italian Hospitals:
      Performance-Based Hygienic Guidance Values (HGVs) Project.
AB  - Antineoplastic drugs (ADs) will continue to represent a potential risk for
      personnel involved in the handling of these compounds and great concerns have
      been raised by the presence of ADs in many surveyed workplaces. Eight hospitals
      were investigated by means of wipe sampling for surface residue determination.
      Each wipe sample was tested for five ADs considered suitable exposure markers.
      Cyclophosphamide (CP), gemcitabine (GEM), 5-fluorouracil (5-FU), platinum
      containing drugs (Pt), and epi-doxorubicin (EPI) contamination levels were
      measured in 85 per cent of the studied pharmacies and 93 per cent of outpatient
      care units (OpCUs). This study showed that 83 out of 349 samples were positive in
      Pharmacies, this proportion being statistically significant (chi2 = 42.9, p <
      0.001). The positive samples provided evidence of at least one substance with
      levels greater than the limit of detection (LOD). The two most frequently
      detected substances were Pt (42%) and CP (30%). These accounted for 72 per cent
      of the whole dataset, followed by 5-FU and GEM. Based on the 90th percentile of
      wipe sampling data distribution, we suggest hygienic guidance values (HGVs) of
      3.6, 1.0, 0.9, and 0.5 ng cm-2 for CP, 5-FU, GEM and Pt, respectively, as the
      best target levels of the surface contamination load in Italian pharmacies. The
      approach of proposing guidance values at the 90th percentile of results obtained
      from workplaces with good hygiene practice was found to be a simple and practical
      way of controlling occupational exposure. HGVs were challenged in this study as
      technical threshold limits to benchmark AD residual surface contamination at
      workplaces.

PMID- 29028252
TI  - Surveillance and Analysis of Occupational Carbon Monoxide Poisoning in the Paris
      Region.
AB  - Objectives: Acute carbon monoxide poisoning is common and often severe. Domestic
      causes have been extensively documented, while occupational exposures have been
      reported less frequently. We analyse occupational carbon monoxide poisonings from
      the available data of the carbon monoxide poisoning surveillance network for
      Paris and its region, and identify predictive factors of severity for
      occupational poisoning in order to identify priority prevention actions. Methods:
      We retrospectively reviewed all events of acute accidental carbon monoxide
      exposures which occurred in the Paris region, at the work place, and notified to
      the surveillance network from 1 January 2005 to 31 December 2011. Results: Over
      the 7-year study period, 362 exposed workers were identified, representing 8.15%
      of all cases of carbon monoxide exposures. The largest number of events occurred
      in the building sector and most commonly affected occupations were craft and
      related trades workers. The most common sources of exposure were internal
      combustion engine equipment that was involved in almost half of cases. Minor
      severity was observed in 86% of cases, and 13% were moderate or more. We identify
      that the use of internal combustion engine equipment was significantly associated
      with increased severity. Conclusions: Occupational carbon monoxide poisoning is
      reported less frequently than domestic poisoning and has different and more
      numerous causes. It can be potentially severe, especially when it is caused by
      internal combustion engine equipment. Information about risks, compliance with
      instructions and cleaning rules, and establishment of collective and individual
      protective equipment would significantly reduce the frequency and severity of
      carbon monoxide poisoning.

PMID- 29028253
TI  - How Accurate and Reliable Are Exposure Models?

PMID- 29028254
TI  - Comparing the Advanced REACH Tool's (ART) Estimates With Switzerland's
      Occupational Exposure Data.
AB  - The Advanced REACH Tool (ART) is the most sophisticated tool used for evaluating
      exposure levels under the European Union's Registration, Evaluation,
      Authorisation and restriction of CHemicals (REACH) regulations. ART provides
      estimates at different percentiles of exposure and within different confidence
      intervals (CIs). However, its performance has only been tested on a limited
      number of exposure data. The present study compares ART's estimates with exposure
      measurements collected over many years in Switzerland. Measurements from 584
      cases of exposure to vapours, mists, powders, and abrasive dusts (wood/stone and
      metal) were extracted from a Swiss database. The corresponding exposures at the
      50th and 90th percentiles were calculated in ART. To characterize the model's
      performance, the 90% CI of the estimates was considered. ART's performance at the
      50th percentile was only found to be insufficiently conservative with regard to
      exposure to wood/stone dusts, whereas the 90th percentile showed sufficient
      conservatism for all the types of exposure processed. However, a trend was
      observed with the residuals, where ART overestimated lower exposures and
      underestimated higher ones. The median was more precise, however, and the
      majority (>=60%) of real-world measurements were within a factor of 10 from ART's
      estimates. We provide recommendations based on the results and suggest further,
      more comprehensive, investigations.

PMID- 29028255
TI  - Wipe Sampling Method and Evaluation of Environmental Variables for Assessing
      Surface Contamination of 10 Antineoplastic Drugs by Liquid Chromatography/Tandem
      Mass Spectrometry.
AB  - This paper describes a novel wipe sampling and high-performance liquid
      chromatography/tandem mass spectrometry (HPLC-MS/MS) method capable of
      simultaneously detecting 10 antineoplastic drugs (5-fluorouracil, oxaliplatin,
      methotrexate, vindesine, ifosfamide, cyclophosphamide, vincristine, vinblastine,
      docetaxel, and paclitaxel). The good overall recoveries and sensitivity values of
      this method along with the comparatively short run time (8 min) allows for its
      use in routine monitoring in health care facilities. The long-term behavior of
      the studied drugs on contaminated surfaces and the effect of surface roughness on
      drug recoveries were studied to gain insights about how these environmental
      variables influence the detection, cleaning, and occupational exposure of these
      drugs. Surfaces with higher roughness parameter (Ra) values (rougher) had the
      lowest recoveries while those with lower Ra (smoother) presented the highest
      recoveries. Long-term assessments evidence distinctive drug behaviors with
      oxaliplatin, vindesine, vincristine, and vinblastine being the less persistent
      drugs (~20% was recovered after 24 h) and docetaxel and paclitaxel the most
      persistent drugs with recoveries of 40% and 80% after 1 month. This information
      indicates the importance of collecting ancillary information about drug usage
      (throughput, timing, cleaning procedures, etc.) to interpret the results in the
      context of potential exposure. Finally, the method was successfully applied to
      evaluate trace surface contamination down to the single picogram per square
      centimeter in multiple work areas within three local health care centers on
      Vancouver Island, Canada.

PMID- 29028256
TI  - A Pilot Study: The UNC Passive Aerosol Sampler in a Working Environment.
AB  - Objectives: Dust is generally sampled on a filter using air pumps, but passive
      sampling could be a cost-effective alternative. One promising passive sampler is
      the University of North Carolina passive aerosol sampler (UNC sampler). The aim
      of this study is to characterize and compare the UNC sampler's performance with
      PM10 and PM2.5 impactors in a working environment. Methods: Area sampling was
      carried out at different mining locations using UNC samplers in parallel with
      PM2.5 and PM10 impactors. Two different collection surfaces, polycarbonate (PC)
      and carbon tabs (CT), were employed for the UNC sampling. Sampling was carried
      out for 4-25 hours. Results: The UNC samplers underestimated the concentrations
      compared to PM10 and PM2.5 impactor data. At the location with the highest
      aerosol concentration, the time-averaged mean of PC showed 24% and CT 35% of the
      impactor result for PM2.5. For PM10, it was 39% with PC and 58% with CT. Sample
      blank values differed between PC and CT. For PM2.5, PC blank values were ~7 times
      higher than those of CT, but only 1.8 times higher for PM10. The blank variations
      were larger for PC than for CT. Conclusions: Particle mass concentrations appear
      to be underestimated by the UNC sampler compared to impactors, more so for PM2.5
      than for PM10. CT may be preferred as a collection surface because the blank
      values were lower and less variable than for PC. Future validations in the
      working environment should include respirable dust sampling.

PMID- 29028257
TI  - Evaluation of Tier One Exposure Assessment Models (ETEAM): Project Overview and
      Methods.

PMID- 29028258
TI  - Between-User Reliability of Tier 1 Exposure Assessment Tools Used Under REACH.
AB  - When applying simple screening (Tier 1) tools to estimate exposure to chemicals
      in a given exposure situation under the Registration, Evaluation, Authorisation
      and restriction of CHemicals Regulation 2006 (REACH), users must select from
      several possible input parameters. Previous studies have suggested that results
      from exposure assessments using expert judgement and from the use of modelling
      tools can vary considerably between assessors. This study aimed to investigate
      the between-user reliability of Tier 1 tools. A remote-completion exercise and in
      person workshop were used to identify and evaluate tool parameters and factors
      such as user demographics that may be potentially associated with between-user
      variability. Participants (N = 146) generated dermal and inhalation exposure
      estimates (N = 4066) from specified workplace descriptions ('exposure
      situations') and Tier 1 tool combinations (N = 20). Interactions between users,
      tools, and situations were investigated and described. Systematic variation
      associated with individual users was minor compared with random between-user
      variation. Although variation was observed between choices made for the majority
      of input parameters, differing choices of Process Category ('PROC') code/activity
      descriptor and dustiness level impacted most on the resultant exposure estimates.
      Exposure estimates ranging over several orders of magnitude were generated for
      the same exposure situation by different tool users. Such unpredictable between
      user variation will reduce consistency within REACH processes and could result in
      under-estimation or overestimation of exposure, risking worker ill-health or the
      implementation of unnecessary risk controls, respectively. Implementation of
      additional support and quality control systems for all tool users is needed to
      reduce between-assessor variation and so ensure both the protection of worker
      health and avoidance of unnecessary business risk management expenditure.

PMID- 29028259
TI  - Stem Cell Transplantation for Frailty.

PMID- 29028260
TI  - pulseR: Versatile computational analysis of RNA turnover from metabolic labeling
      experiments.
AB  - Motivation: Metabolic labelling of RNA is a well-established and powerful method
      to estimate RNA synthesis and decay rates. The pulseR R package simplifies the
      analysis of RNA-seq count data that emerge from corresponding pulse-chase
      experiments. Results: The pulseR package provides a flexible interface and
      readily accommodates numerous different experimental designs. To our knowledge,
      it is the first publicly available software solution that models count data with
      the more appropriate negative-binomial model. Moreover, pulseR handles labelled
      and unlabelled spike-in sets in its workflow and accounts for potential labeling
      biases (e.g. number of uridine residues). Availability and implementation: The
      pulseR package is freely available at https://github.com/dieterich-lab/pulseR
      under the GPLv3.0 licence. Contact: a.uvarovskii@uni-heidelberg.de or
      christoph.dieterich@uni-heidelberg.de. Supplementary information: Supplementary
      data are available at Bioinformatics online.

PMID- 29028261
TI  - Panoptes: web-based exploration of large scale genome variation data.
AB  - Motivation: The size and complexity of modern large-scale genome variation
      studies demand novel approaches for exploring and sharing the data. In order to
      unlock the potential of these data for a broad audience of scientists with
      various areas of expertise, a unified exploration framework is required that is
      accessible, coherent and user-friendly. Results: Panoptes is an open-source
      software framework for collaborative visual exploration of large-scale genome
      variation data and associated metadata in a web browser. It relies on technology
      choices that allow it to operate in near real-time on very large datasets. It can
      be used to browse rich, hybrid content in a coherent way, and offers interactive
      visual analytics approaches to assist the exploration. We illustrate its
      application using genome variation data of Anopheles gambiae, Plasmodium
      falciparum and Plasmodium vivax. Availability and implementation: Freely
      available at https://github.com/cggh/panoptes, under the GNU Affero General
      Public License. Contact: paul.vauterin@gmail.com.

PMID- 29028262
TI  - TSIS: an R package to infer alternative splicing isoform switches for time-series
      data.
AB  - Summary: An alternative splicing isoform switch is where a pair of transcript
      isoforms reverse their relative expression abundances in response to external or
      internal stimuli. Although computational methods are available to study
      differential alternative splicing, few tools for detection of isoform switches
      exist and these are based on pairwise comparisons. Here, we provide the TSIS R
      package, which is the first tool for detecting significant transcript isoform
      switches in time-series data. The main steps of TSIS are to search for the
      isoform switch points in the time-series, characterize the switches and filter
      the results with user input parameters. All the functions are integrated into a
      Shiny App for ease of implementation of the analysis. Availability and
      implementation: The TSIS package is available on GitHub:
      https://github.com/wyguo/TSIS. Contact: runxuan.zhang@hutton.ac.uk.

PMID- 29028263
TI  - Epigenomic annotation-based interpretation of genomic data: from enrichment
      analysis to machine learning.
AB  - Motivation: One of the goals of functional genomics is to understand the
      regulatory implications of experimentally obtained genomic regions of interest
      (ROIs). Most sequencing technologies now generate ROIs distributed across the
      whole genome. The interpretation of these genome-wide ROIs represents a challenge
      as the majority of them lie outside of functionally well-defined protein coding
      regions. Recent efforts by the members of the International Human Epigenome
      Consortium have generated volumes of functional/regulatory data (reference
      epigenomic datasets), effectively annotating the genome with epigenomic
      properties. Consequently, a wide variety of computational tools has been
      developed utilizing these epigenomic datasets for the interpretation of genomic
      data. Results: The purpose of this review is to provide a structured overview of
      practical solutions for the interpretation of ROIs with the help of epigenomic
      data. Starting with epigenomic enrichment analysis, we discuss leading tools and
      machine learning methods utilizing epigenomic and 3D genome structure data. The
      hierarchy of tools and methods reviewed here presents a practical guide for the
      interpretation of genome-wide ROIs within an epigenomic context. Contact:
      mikhail.dozmorov@vcuhealth.org. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29028264
TI  - TeachEnG: a Teaching Engine for Genomics.
AB  - Motivation: Bioinformatics is a rapidly growing field that has emerged from the
      synergy of computer science, statistics and biology. Given the interdisciplinary
      nature of bioinformatics, many students from diverse fields struggle with
      grasping bioinformatic concepts only from classroom lectures. Interactive tools
      for helping students reinforce their learning would be thus desirable. Here, we
      present an interactive online educational tool called TeachEnG (acronym for
      Teaching Engine for Genomics) for reinforcing key concepts in sequence alignment
      and phylogenetic tree reconstruction. Our instructional games allow students to
      align sequences by hand, fill out the dynamic programming matrix in the Needleman
      Wunsch global sequence alignment algorithm, and reconstruct phylogenetic trees
      via the maximum parsimony, Unweighted Pair Group Method with Arithmetic mean
      (UPGMA) and Neighbor-Joining algorithms. With an easily accessible interface and
      instant visual feedback, TeachEnG will help promote active learning in
      bioinformatics. Availability and implementation: TeachEnG is freely available at
      http://teacheng.illinois.edu. The source code is available from
      https://github.com/KnowEnG/TeachEnG under the Artistic License 2.0. It is written
      in JavaScript and compatible with Firefox, Safari, Chrome and Microsoft Edge.
      Contact: songj@illinois.edu.

PMID- 29028265
TI  - StereoGene: rapid estimation of genome-wide correlation of continuous or interval
      feature data.
AB  - Motivation: Genomics features with similar genome-wide distributions are
      generally hypothesized to be functionally related, for example, colocalization of
      histones and transcription start sites indicate chromatin regulation of
      transcription factor activity. Therefore, statistical algorithms to perform
      spatial, genome-wide correlation among genomic features are required. Results:
      Here, we propose a method, StereoGene, that rapidly estimates genome-wide
      correlation among pairs of genomic features. These features may represent high
      throughput data mapped to reference genome or sets of genomic annotations in that
      reference genome. StereoGene enables correlation of continuous data directly,
      avoiding the data binarization and subsequent data loss. Correlations are
      computed among neighboring genomic positions using kernel correlation.
      Representing the correlation as a function of the genome position, StereoGene
      outputs the local correlation track as part of the analysis. StereoGene also
      accounts for confounders such as input DNA by partial correlation. We apply our
      method to numerous comparisons of ChIP-Seq datasets from the Human Epigenome
      Atlas and FANTOM CAGE to demonstrate its wide applicability. We observe the
      changes in the correlation between epigenomic features across developmental
      trajectories of several tissue types consistent with known biology and find a
      novel spatial correlation of CAGE clusters with donor splice sites and with
      poly(A) sites. These analyses provide examples for the broad applicability of
      StereoGene for regulatory genomics. Availability and implementation: The
      StereoGene C ++ source code, program documentation, Galaxy integration scripts
      and examples are available from the project homepage
      http://stereogene.bioinf.fbb.msu.ru/. Contact: favorov@sensi.org. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29028266
TI  - CircPro: an integrated tool for the identification of circRNAs with protein
      coding potential.
AB  - Summary: Circular RNAs (circRNAs), a novel class of endogenous RNAs, are
      widespread in eukaryotic cells. Emerging roles in diverse biological processes
      suggest that circRNA is a promising key player in RNA world. Most circRNAs are
      generated through back-splicing of pre-mRNAs, forming a covalently closed loop
      structure with no 5' caps or 3' polyadenylated tails. In addition, most circRNAs
      were not associated with translating ribosomes, therefore, circRNAs were deemed
      to be noncoding. However, the latest research findings revealed that some
      circRNAs could generate proteins in vivo, which expands the landscape of
      transcriptome and proteome. To gain insights into the new area of circRNA
      translation, we introduce an integrated tool capable of detecting circRNAs with
      protein-coding potential from high-throughput sequencing data. Availability and
      implementation: CircPro is available at http://bis.zju.edu.cn/CircPro. Contact:
      mchen@zju.edu.cn. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 29028267
TI  - VariantTools: an extensible framework for developing and testing variant callers.
AB  - Motivation: Variant calling is the complex task of separating real polymorphisms
      from errors. The appropriate strategy will depend on characteristics of the
      sample, the sequencing methodology and on the questions of interest. Results: We
      present VariantTools, an extensible framework for developing and testing variant
      callers. There are facilities for reproducibly tallying, filtering, flagging and
      annotating variants. The tools are extensible, modular and flexible, so that they
      are tunable to particular use cases, and they interoperate with existing analysis
      software so that they can be embedded in established work flows. Availability and
      implementation: VariantTools is available from http://www.bioconductor.org/.
      Contact: michafla@gene.com. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29028268
TI  - Relationship between the Mediterranean dietary pattern and musculoskeletal health
      in children, adolescents, and adults: systematic review and evidence map.
AB  - Context: An understanding of the modifiable effects of diet on bone and skeletal
      muscle mass and strength over the life course will help inform strategies to
      reduce age-related fracture risk. The Mediterranean diet is rich in nutrients
      that may be important for optimal musculoskeletal health. The aim of this
      systematic review was to investigate the relationship between a Mediterranean
      diet and musculoskeletal outcomes (fracture, bone density, osteoporosis,
      sarcopenia) in any age group. Ten electronic databases were searched. Randomized
      controlled trials and prospective cohort studies that investigated a traditional
      Mediterranean diet, published in any language, were eligible. Studies using other
      designs or other definitions of the Mediterranean diet were collated separately
      in an evidence map. Details on study design, methods, population, dietary
      intervention or exposure, length of follow-up, and effect on or association with
      musculoskeletal outcomes were extracted. The search yielded 1738 references. Data
      from eligible randomized controlled trials (n = 0) and prospective cohort studies
      (n = 3) were synthesized narratively by outcome for the systematic review. Two of
      these studies reported on hip fracture incidence, but results were contradictory.
      A third study found no association between the Mediterranean diet and sarcopenia
      incidence. Overall, the systematic review and evidence map demonstrate a lack of
      research to understand the relationship between the Mediterranean diet and
      musculoskeletal health in all ages. PROSPERO registration number
      IDCRD42016037038.

PMID- 29028269
TI  - Acceptance and adoption of biofortified crops in low- and middle-income
      countries: a systematic review.
AB  - Context: Biofortification of staple crops is a promising strategy for increasing
      the nutrient density of diets in order to improve human health. The willingness
      of consumers and producers to accept new crop varieties will determine whether
      biofortification can be successfully implemented. This review assessed sensory
      acceptance and adoption of biofortified crops and the determining factors for
      acceptance and adoption among consumers and producers in low- and middle-income
      countries. PubMed, Scopus, and Web of Science were searched for published
      reports. Unpublished studies were identified using an internet search. From a
      total of 1669 records found, 72 primary human research studies published in
      English or Spanish met the criteria for inclusion. : Data were extracted from
      each identified study using a standardized form. Sensory acceptability (n = 40)
      was the most common topic of the studies, followed by determinants of acceptance
      (n = 25) and adoption (n = 21). Of crops included in the studies, sweet potato
      and maize were the most studied, whereas rice and pearl-millet were the least
      investigated. Overall, sensory acceptance was good, and availability and
      information on health benefits of the crops were the most important determinants
      of acceptance and adoption. : Changes to the sensory qualities of a crop,
      including changes in color, did not act as an obstacle to acceptance of
      biofortified crops. Future studies should look at acceptance of biofortified
      crops after they have been disseminated and introduced on a wide-scale.

PMID- 29028271
TI  - Influence of adipose tissue mass on bone mass in an overweight or obese
      population: systematic review and meta-analysis.
AB  - Context: The scientific literature shows conflicting evidence about the
      relationship between adiposity and bone mass in overweight and obese populations.
      The aim of this review was to quantify the correlation between adipose mass
      (absolute and relative) and bone mineral density (BMD) in overweight and obese
      populations. Three databases were searched electronically. In addition, reference
      lists of relevant articles were screened. A total of 16 studies, comprising 2587
      participants and 75 correlation coefficients were selected for inclusion in the
      review. Data were extracted from each study using a standardized form. Multilevel
      modeling indicated opposing relationships between BMD and adiposity: absolute
      adiposity correlated positively, and relative adiposity negatively, with BMD. Sex
      and age were the primary moderators of these relationships. Strong evidence
      supported a negative relationship between relative adipose mass and BMD in men (R
      = -0.37; 95%CI, -0.57 to -0.12) and in those aged less than 25 years (R = -0.28;
      95%CI, -0.45 to -0.08). To prevent bone loss in overweight and obese populations,
      nutrition- and exercise-based interventions that focus on a controlled reduction
      of adipose mass with concomitant preservation of lean mass are recommended. :
      PROSPERO no. CRD42015024313.

PMID- 29028270
TI  - Critical review of the emerging research evidence on agricultural biodiversity,
      diet diversity, and nutritional status in low- and middle-income countries.
AB  - The declining diversity of agricultural production and food supplies worldwide
      may have important implications for global diets. The primary objective of this
      review is to assess the nature and magnitude of the associations of agricultural
      biodiversity with diet quality and anthropometric outcomes in low- and middle
      income countries. A comprehensive review of 5 databases using a priori exclusion
      criteria and application of a systematic, qualitative analysis to the findings of
      identified studies revealed that agricultural biodiversity has a small but
      consistent association with more diverse household- and individual-level diets,
      although the magnitude of this association varies with the extent of existing
      diversification of farms. Greater on-farm crop species richness is also
      associated with small, positive increments in young child linear stature.
      Agricultural diversification may contribute to diversified diets through both
      subsistence- and income-generating pathways and may be an important strategy for
      improving diets and nutrition outcomes in low- and middle-income countries. Six
      research priorities for future studies of the influence of agricultural
      biodiversity on nutrition outcomes are identified based on gaps in the research
      literature.

PMID- 29028272
TI  - Dietary carbohydrates, components of energy balance, and associated health
      outcomes.
AB  - The role of dietary carbohydrates in the development of obesity and associated
      metabolic dysfunction has recently been questioned. Within the last decade, the
      Scientific Advisory Committee on Nutrition carried out a comprehensive evaluation
      of the role of dietary carbohydrates in human health. The current review aims to
      complement and extend this report by providing specific consideration of the
      effects of the component parts of energy balance, their interactions, and their
      culmination on energy storage and health. PubMed was searched for all published
      trials that had a minimum follow-up period of 3 months and were designed to
      manipulate dietary carbohydrate intake, irrespective of resultant differences in
      absolute carbohydrate dose (grams per day). Dietary carbohydrate manipulation has
      little effect on the individual components of energy balance that have been
      assessed. However, the role of dietary carbohydrates in influencing physical
      activity has yet to be assessed using gold-standard measurement tools. Moreover,
      adherence to a diet of modified carbohydrate content has not been found to result
      in a consistent pattern of changes in weight or indirect measures of metabolic
      health. However, certain markers of cardiovascular disease risk (ie, blood
      triglycerides and high-density lipoprotein cholesterol) may respond positively to
      a reduction in dietary carbohydrates.

PMID- 29028273
TI  - Corrigendum.

PMID- 29028274
TI  - THE 2017 13TH ANNUAL DAVID W. KENNEDY, MD, LECTURE The evolution of outcomes in
      sinus surgery for chronic rhinosinusitis: past, present, and future.
AB  - This is an edited transcript from the 2017 13th Annual David W. Kennedy, MD,
      Lecture, presented to the American Rhinologic Society during the 63rd Annual
      Meeting.

PMID- 29028275
TI  - Exposure reductions associated with introduction of solar lamps to kerosene lamp
      using households in Busia County, Kenya.
AB  - Solar lamps are a clean and potentially cost-effective alternative to polluting
      kerosene lamps used by millions of families in developing countries. By how much
      solar lamps actually reduce exposure to pollutants, however, has not been
      examined. Twenty households using mainly kerosene for lighting were enrolled
      through a secondary school in Busia County, Kenya. Personal PM2.5 and CO
      concentrations were measured on a school pupil and an adult in each household,
      before and after provision of 3 solar lamps. PM2.5 concentrations were measured
      in main living areas, pupils' bedrooms, and kitchens. Usage sensors measured use
      of kerosene and solar lighting devices. Ninety percent of baseline kerosene lamp
      use was displaced at 1-month follow-up, corresponding to average PM2.5 reductions
      of 61% and 79% in main living areas and pupils' bedrooms, respectively. Average
      48-h exposure to PM2.5 fell from 210 to 104 MUg/m3 (-50%) among adults, and from
      132 to 35 MUg/m3 (-73%) among pupils. Solar lamps displaced most kerosene lamp
      use in at least the short term. If sustained, this could mitigate health impacts
      of household air pollution in some contexts. Achieving safe levels of exposure
      for all family members would likely require also addressing use of solid-fuel
      stoves.

PMID- 29028276
TI  - Enhancing antibiotic stewardship by tackling "spurious" penicillin allergy.
AB  - Approximately 90-99% of patients with a label of penicillin allergy (PenA) are
      not allergic when comprehensively investigated. An inaccurate label of PenA has
      major public health implications-longer hospital stay, more frequent hospital
      admissions, greater use of fluoroquinolones, glycopeptides, cephalosporins and
      other expensive antibiotics resulting in significantly higher costs to the health
      service and predisposing to Clostridium difficile, methicillin-resistant
      Staphylococcus aureus infections and vancomycin-resistant enterococcus. We
      describe lessons learnt from recent studies regarding possible reasons
      contributing to an inaccurate label of PenA as well as propose a concerted
      multidisciplinary approach to address this important public health problem. Given
      the unmet need for allergy services in the UK and several other countries and
      knowledge gaps regarding PenA amongst healthcare professionals, we describe the
      potential role for a computerized clinical decision support system to enable non
      specialists rapidly identify and de-label "low-risk" hospitalized patients with a
      label of PenA thereby obviating the need for allergy tests. This approach however
      needs rigorous evaluation for feasibility, safety, patient and physician
      acceptability, cost-effectiveness and its compatibility with information
      technology systems currently employed in the health service.

PMID- 29028277
TI  - Associations between daily cooking duration and the prevalence of diabetes and
      prediabetes in a middle-aged and elderly Chinese population: A cross-sectional
      study.
AB  - Experimental and epidemiological studies indicated that ambient air pollution was
      positively associated with diabetes. Few studies investigated the associations
      between household air pollution, for example, daily cooking duration and diabetes
      or prediabetes. We conducted a cross-sectional study to investigate the
      associations of daily cooking duration with the prevalence of diabetes and
      prediabetes among a middle-aged and elderly population. A total of 26 089
      individuals (11 250 males and 14 839 females) derived from the Dongfeng-Tongji
      cohort study were included. Daily cooking duration was assessed by questionnaire.
      Diabetes and prediabetes were identified according to the criterion of American
      Diabetes Association. No significant association was observed between daily
      cooking duration and the prevalence risk of diabetes (odds ratio[OR] = 0.97, 95%
      confidence interval[CI]: [0.81-1.16], P for trend = .74); however, longer daily
      cooking duration was associated with higher prevalence risk of prediabetes (OR =
      1.26, 95% CI: 1.07-1.47; P for trend = .003) and hyperglycemia (OR = 1.21, 95%
      CI: 1.05-1.41; P for trend = .005). Our study suggested that daily cooking
      duration was not associated with diabetes but with higher prevalence risk of
      prediabetes/hyperglycemia in a middle-aged and elderly Chinese population.

PMID- 29028278
TI  - Functional variants in intercellular adhesion molecule-1 and toll-like receptor-4
      genes are more frequent in children with febrile urinary tract infection with
      renal parenchymal involvement.
AB  - AIM: We studied the functional polymorphisms of intercellular adhesion molecule-1
      (ICAM-1) and toll-like receptor-4 (TLR-4) genes and risk of acute pyelonephritis
      (APN) in children attending Assiut University Children's Hospitals, Egypt, from
      2011 to 2015. METHODS: Urinary tract infections (UTIs) were diagnosed in 380
      children: 98 had APN and 282 had lower UTIs. Four single-nucleotide polymorphisms
      in ICAM-1 and TLR-4 genes were genotyped in all subjects: ICAM-1 rs1799969
      Gly241Arg, ICAM-1 rs5498 Glu469Lys, TLR-4 rs4896791 Thr399Ile and TLR-4 rs4896790
      Asp299Gly. RESULTS: Patients with APN were significantly more likely to have AA
      genotype of the ICAM-1 rs5498 (1462 A/G) polymorphism (p = 0.04) than children
      with lower UTIs and the TLR-4 Asp299Gly GG genotype (p = 0.002) and G allele (p =
      0.006) than healthy controls. The association with the ICAM-1 Glu469Lys (1462A/G)
      was less evident. The GG genotype was associated with a modest relative risk of
      1.4 (p = 0.1) of developing APN, but was not an independent odds ratio, at 1.2 (p
      = 0.48). CONCLUSION: Functional variants in ICAM-1 and TLR-4 genes were
      increasingly common in children with febrile UTIs with renal parenchymal
      involvement, but the ICAM-1 Glu469Lys (1462A/G) association was less evident.
      TLR4 Asp299Gly might independently increase renal parenchymal infection rather
      than renal scarring.

PMID- 29028279
TI  - Liver elastography malignancy prediction score for noninvasive characterization
      of focal liver lesions.
AB  - BACKGROUND & AIMS: To analyse elastographic characteristics of focal liver
      lesions (FLL)s and diagnostic performance of real-time two-dimensional shear-wave
      elastography (RT-2D-SWE) in order to differentiate benign and malignant FLLs.
      METHODS: Consecutive patients diagnosed with FLL by abdominal ultrasound (US)
      underwent RT-2D-SWE of FLL and non-infiltrated liver by intercostal approach over
      the right liver lobe. The nature of FLL was determined by diagnostic work-up,
      including at least one contrast-enhanced imaging modality (MDCT/MRI), check-up of
      target organs when metastatic disease was suspected and FLL biopsy in
      inconclusive cases. RESULTS: We analysed 196 patients (median age 60 [range 50
      68], 50.5% males) with 259 FLLs (57 hepatocellular carcinomas, 17
      cholangiocarcinomas, 94 metastases, 71 haemangiomas, 20 focal nodular
      hyperplasia) of which 70 (27%) were in cirrhotic liver. Malignant lesions were
      stiffer (P < .001) with higher variability in intralesional stiffness (P = .001).
      The best performing cut-off of lesion stiffness was 22.3 kPa (sensitivity 83%;
      specificity 86%; positive predictive value [PPV] 91.5%; negative predictive value
      [NPV] 73%) for malignancy. Lesion stiffness <14 kPa had NPV of 96%, while values
      >32.5 kPa had PPV of 96% for malignancy. Lesion stiffness, lesion/liver stiffness
      ratio and lesion stiffness variability significantly predicted malignancy in
      stepwise logistic regression (P < .05), and were used to construct a new Liver
      Elastography Malignancy Prediction (LEMP) score with accuracy of 96.1% in
      validation cohort (online calculator available at http://bit.do/lemps).
      CONCLUSION: The comprehensive approach demonstrated in this study enables correct
      differentiation of benign and malignant FLL in 96% of patients by using RT-2D
      SWE.

PMID- 29028280
TI  - Temporal changes in soil C-N-P stoichiometry over the past 60 years across
      subtropical China.
AB  - Controlled experiments have shown that global changes decouple the biogeochemical
      cycles of carbon (C), nitrogen (N), and phosphorus (P), resulting in shifting
      stoichiometry that lies at the core of ecosystem functioning. However, the
      response of soil stoichiometry to global changes in natural ecosystems with
      different soil depths, vegetation types, and climate gradients remains poorly
      understood. Based on 2,736 observations along soil profiles of 0-150 cm depth
      from 1955 to 2016, we evaluated the temporal changes in soil C-N-P stoichiometry
      across subtropical China, where soils are P-impoverished, with diverse
      vegetation, soil, and parent material types and a wide range of climate
      gradients. We found a significant overall increase in soil total C concentration
      and a decrease in soil total P concentration, resulting in increasing soil C:P
      and N:P ratios during the past 60 years across all soil depths. Although average
      soil N concentration did not change, soil C:N increased in topsoil while
      decreasing in deeper soil. The temporal trends in soil C-N-P stoichiometry
      differed among vegetation, soil, parent material types, and spatial climate
      variations, with significantly increased C:P and N:P ratios for evergreen
      broadleaf forest and highly weathered Ultisols, and more pronounced temporal
      changes in soil C:N, N:P, and C:P ratios at low elevations. Our sensitivity
      analysis suggests that the temporal changes in soil stoichiometry resulted from
      elevated N deposition, rising atmospheric CO2 concentration and regional warming.
      Our findings revealed that the responses of soil C-N-P and stoichiometry to long
      term global changes have occurred across the whole soil depth in subtropical
      China and the magnitudes of the changes in soil stoichiometry are dependent on
      vegetation types, soil types, and spatial climate variations.

PMID- 29028281
TI  - Usefulness of the index of NASH - ION for the diagnosis of steatohepatitis in
      patients with non-alcoholic fatty liver: An external validation study.
AB  - BACKGROUND & AIMS: The non-invasive identification of steatohepatitis (NASH) in
      patients with Non-Alcoholic Fatty Liver Disease is an unmet need in clinical
      practice. Index of NASH (ION) is a new tool for the prediction of NASH. We aimed
      to externally validate ION and to compare it with CK-18. Since necroinflammation
      precedes fibrosis, we also tested ION in combination with non-invasive tools for
      fibrosis. METHODS: We analysed data from 292 Italian patients (169 Southern
      cohort, and 123 Northern cohort) with an histological diagnosis of NAFLD. The
      ION, FIB-4 and NFS scores were calculated according to published algorithms.
      Serum cytokeratin18-Aspartate396 levels and liver stiffness (LS) by Fibroscan
      were assessed within three months from liver biopsy. RESULTS: The diagnostic
      accuracy of ION for the identification of NASH was not as satisfactory as
      reported (area under the ROC curve, AUROC = 0.687 [95% CI = 0.62-0.75]). The
      proposed cut-off value >=50 showed a poor sensitivity (Se) (28%) and a good
      specificity (Sp) (92%), with a positive predictive value (PPV) of 91% and a
      negative predictive value (NPV) of 30%. A new cut-off value >26 improved Se (73%)
      but decreased Sp (60%) (PPV of 84% and a NPV of 43%). ION performed slightly
      better in obese NAFLD (AUROC = 0.700). The combination of ION and markers of
      fibrosis did not improve the identification of advanced liver disease.
      CONCLUSIONS: ION is not feasible for the non-invasive diagnosis of NASH across
      different populations of NAFLD patients, mainly because its limited
      reproducibility in non-obese subjects.

PMID- 29028282
TI  - Characteristics of Quality Improvement Champions in Nursing Homes: A Systematic
      Review With Implications for Evidence-Based Practice.
AB  - BACKGROUND: Improving care quality while reducing cost has always been a focus of
      nursing homes. Certified nursing assistants comprise the largest proportion of
      the workforce in nursing homes and have the potential to contribute to the
      quality of care provided. Quality improvement (QI) initiatives using certified
      nursing assistants as champions have the potential to improve job satisfaction,
      which has been associated with care quality. AIMS: To identify the role, use and
      preparation of champions in a nursing home setting as a way of informing future
      QI strategies in nursing homes. METHODS: A systematic literature review. Medical
      Subject Headings and text words for "quality improvement" were combined with
      those for "champion*" to search Medline, CINAHL, Joanna Briggs Institute, MedLine
      In-Process, and other Nonindexed Citations. After duplicates were removed, a
      total of 337 potential articles were identified for further review. After full
      text review, seven articles from five original studies met inclusion criteria and
      were included in the synthesis. RESULTS: Various types of QI initiatives and
      implementation strategies were used together with champions. Champions were
      identified by study authors as one of the single most effective strategies
      employed in all studies. The majority of studies described the champion role as
      that of a leader, who fosters and reinforces changes for improvement. Although
      all the included studies suggested that implementing nurse or aid champions in
      their QI initiatives were important facilitators of success, how the champions
      were selected and trained in their role is either missing or not described in any
      detail in the studies included in the review. LINKING EVIDENCE TO ACTION:
      Utilizing certified nursing assistants as QI champions can increase participation
      in QI projects and has the potential to improve job satisfaction and contribute
      to improve quality of care and improved patient outcomes in nursing homes.

PMID- 29028283
TI  - Implementation of buffy-coat-derived pooled platelet concentrates for internal
      quality control of light transmission aggregometry: a proof of concept study.
AB  - : Essentials In platelet function testing, standardized internal controls (IQC)
      are not commercially provided. Platelet function testing was performed daily on
      aliquoted pooled platelet concentrates. Pooled platelet concentrates showed
      stability for control purposes from Monday to Friday. Pooled platelet
      concentrates provide the necessary steadiness to serve as IQC material. SUMMARY:
      Background Standardized commercially available control material for internal
      quality control (IQC) of light transmission aggregometry (LTA) is still lacking.
      Moreover, the availability of normal blood donors to provide fresh platelets is
      difficult in small laboratories, where 'volunteers' may be in short supply.
      Objectives To evaluate the implementation of buffy-coat-derived pooled platelet
      concentrates (PCs) for IQC material for LTA. Methods We used buffy-coat-derived
      pooled PCs from the blood bank as IQC material for LTA. On each weekend one PC
      was prepared (> 200 mL) and aliquoted from the original storage bag on a daily
      basis in four baby bags (40-50 mL), which were delivered from Monday to Friday to
      our laboratory. The IQC measurements of at least 85 work-weeks (from Monday to
      Friday) were evaluated with this new IQC material. LTA was performed on a four
      channel Chronolog 700 Aggregometer (Chronolog Corporation, Havertown, PA, USA)
      (agonists: collagen, adenosine diphosphate [ADP], arachidonic acid [AA] and
      thrombin receptor activator peptide-6 [TRAP-6]). Results The medians of platelet
      aggregation from IQC measurements with collagen, ADP and AA from Monday to Friday
      were 68.0-59.5, 3.0-2.0 and 51.0-50.0%, respectively, and the mean of platelet
      aggregation with TRAP-6 was 71.2-66.4%. Conclusions Buffy-coat-derived pooled PCs
      serve as a reliable and robust IQC material for LTA measurements and would be
      beneficial for the whole laboratory procedure and employees' safety.

PMID- 29028284
TI  - Tissue factor-bearing microparticles and inflammation: a potential mechanism for
      the development of venous thromboembolism in cancer.
AB  - Cancer is associated with an increased risk of venous thromboembolism (VTE); the
      exact mechanisms for the induction of VTE remain to be fully elucidated, but it
      is widely acknowledged that tissue factor (TF)-bearing microparticles (TF-MPs)
      may play a significant role. However, TF-MPs have yet to be accepted as a genuine
      biomarker for cancer-associated VTE, as the presence of elevated TF-MP levels is
      not always accompanied by thrombosis; interestingly, in certain cases,
      particularly in pancreatic cancer, VTE seems to be more likely in the context of
      acute inflammation. Although several potential mechanisms for the development of
      VTE in cancer have been postulated, this review explores the homeostatic
      disruption of TF-MPs, as the main reservoir of bloodborne TF, in the context of
      cancer and inflammation, and considers the abrogated responses of the activated
      endothelium and mononuclear phagocyte system in mediating this disruption.

PMID- 29028285
TI  - Trends in the incidence rate, type and treatment of surgically verified
      endometriosis - a nationwide cohort study.
AB  - INTRODUCTION: To study the trends in incidence rate, type and surgical treatment,
      and patient characteristics of surgically verified endometriosis during 1987
      2012. MATERIAL AND METHODS: This is a register-based cohort study. We identified
      women receiving their first diagnosis of endometriosis in surgery from the
      Finnish Hospital Discharge Register (FHDR). Quality of the FHDR records was
      assessed bidirectionally. The age-standardized incidence rates of the first
      surgically verified endometriosis was assessed by calendar year. RESULTS: The
      cohort comprises 49 956 women. The quality assessment suggested the FHDR data to
      be of good quality. The most common diagnosis, ovarian endometriosis (46%), was
      associated with highest median age 38.5 years (interquartile range 31.0-44.8) and
      the second most common diagnosis, peritoneal endometriosis (40%), with median age
      34.9 years (28.6-41.7). Between 1987 and 2012, a decrease was observed in the
      median age, from 38.8 (32.3-43.6) to 34.0 (28.9-41.0) years, and in the age
      standardized incidence rate from 116 [95% confidence interval (CI) 112-121] to 45
      (42-48) per 100 000 women. The proportion of hysterectomy as a first surgical
      treatment decreased from 38 to 19%, whereas that of laparoscopy increased from 42
      to 73% when comparing 1987-1995 with 1996-2012. CONCLUSIONS: This nationwide
      cohort of surgically verified endometriosis showed a decrease in the incidence
      rate and in the patient age at the time of first diagnosis, even though the
      proportion of laparoscopy has increased. The number of hysterectomies has
      decreased. These changes are likely to reflect the evolving diagnostics,
      increasing awareness of endometriosis, and effective use of medical treatment
      before surgery.

PMID- 29028286
TI  - Doppler-guided goal-directed fluid therapy does not affect intestinal cell damage
      but increases global gastrointestinal perfusion in colorectal surgery: a
      randomized controlled trial.
AB  - AIM: Individualized, goal-directed fluid therapy (GDFT), based on Doppler
      measurements of stroke volume, has been proposed as a treatment strategy in terms
      of reducing complications, mortality and length of hospital stay in major bowel
      surgery. We studied the effect of Doppler-guided GDFT on intestinal damage as
      compared with standard postoperative fluid replacement. METHOD: Patients
      undergoing elective colorectal resection for malignancy were randomized either to
      standard intra- and postoperative fluid therapy or to standard fluid therapy with
      additional Doppler-guided GDFT. The primary outcome was intestinal epithelial
      cell damage measured by plasma levels of intestinal fatty acid-binding protein (I
      FABP). Global gastrointestinal perfusion was measured by gastric tonometry,
      expressed as regional (gastric) minus arterial CO2 -gap (Pr-a CO2 -gap). RESULTS:
      I-FABP levels were not significantly different between the intervention group and
      the control group (respectively, 440.8 (251.6) pg/ml and 522.4 (759.9) pg/ml, P =
      0.67). Mean areas under the curve (AUCs) of intra-operative Pr-a CO2 -gaps were
      significantly lower in the intervention group than in the control group (P =
      0.01), indicating better global gastrointestinal perfusion in the intervention
      group. Moreover, the mean intra-operative Pr-a CO2 -gap peak in the intervention
      group was 0.5 (1.0) kPa, which was significantly lower than the mean peak in the
      control group, of 1.4 (1.4) kPa (P = 0.03). CONCLUSION: Doppler-guided GDFT
      during and in the first hours after elective colorectal surgery for malignancy
      increases global gastrointestinal perfusion, as measured by Pr-a CO2 -gap.

PMID- 29028287
TI  - A validated model for the 22-item Sino-Nasal Outcome Test subdomain structure in
      chronic rhinosinusitis.
AB  - BACKGROUND: Previous studies have identified subdomains of the 22-item Sino-Nasal
      Outcome Test (SNOT-22), reflecting distinct and largely independent categories of
      chronic rhinosinusitis (CRS) symptoms. However, no study has validated the
      subdomain structure of the SNOT-22. This study aims to validate the existence of
      underlying symptom subdomains of the SNOT-22 using confirmatory factor analysis
      (CFA) and to develop a subdomain model that practitioners and researchers can use
      to describe CRS symptomatology. METHODS: A total of 800 patients with CRS were
      included into this cross-sectional study (400 CRS patients from Boston, MA, and
      400 CRS patients from Reno, NV). Their SNOT-22 responses were analyzed using
      exploratory factor analysis (EFA) to determine the number of symptom subdomains.
      A CFA was performed to develop a validated measurement model for the underlying
      SNOT-22 subdomains along with various tests of validity and goodness of fit.
      RESULTS: EFA demonstrated 4 distinct factors reflecting: sleep, nasal,
      otologic/facial pain, and emotional symptoms (Cronbach's alpha, >0.7; Bartlett's
      test of sphericity, p < 0.001; Kaiser-Meyer-Olkin >0.90), independent of
      geographic locale. The corresponding CFA measurement model demonstrated excellent
      measures of fit (root mean square error of approximation, <0.06; standardized
      root mean square residual, <0.08; comparative fit index, >0.95; Tucker-Lewis
      index, >0.95) and measures of construct validity (heterotrait-monotrait [HTMT]
      ratio, <0.85; composite reliability, >0.7), again independent of geographic
      locale. CONCLUSION: The use of the 4-subdomain structure for SNOT-22 (reflecting
      sleep, nasal, otologic/facial pain, and emotional symptoms of CRS) was validated
      as the most appropriate to calculate SNOT-22 subdomain scores for patients from
      different geographic regions using CFA.

PMID- 29028288
TI  - Hypochlorous acid is antipruritic and anti-inflammatory in a mouse model of
      atopic dermatitis.
AB  - BACKGROUND: It has been reported that topical hypochlorous acid (HOCl)
      formulations lead to relief of itch in human patients with atopic dermatitis;
      however, the specific antipruritic mechanism of action remains unclear.
      OBJECTIVE: To confirm itch relief and reduction of lesions in a mouse model of
      atopic dermatitis and to elucidate possible HOCl's mode of action. METHODS: In
      this study, the effects of topical administration of HOCl hydrogel (0.05%) on
      atopic dermatitis-like lesions in NC/Nga mice model as well as in vitro effects
      of HOCl on dorsal root ganglia neurons and mouse bone marrow-derived dendritic
      cells (mBMDCs) were investigated. NC/Nga mice were sensitized with house dust
      mite allergen and treated topically with HOCl hydrogel both preventively and
      therapeutically against established lesions. Allergen challenge was continued
      during HOCl hydrogel application. RESULTS: Treatment with HOCl hydrogel prevented
      the development of lesions and scratching bouts during the whole observation
      period. When administered after full development of lesions, HOCl reduced lesions
      and scratching behaviour to a similar extent as a positive control 0.1%
      betamethasone dipropionate ointment. The reduced inflammatory response by HOCl
      treatment was demonstrated by reduced secretion of inflammatory cytokines in
      affected skin tissue from NC/Nga mice. In addition, HOCl significantly reduced IL
      12 production in mBMDC. The diminished scratching behaviour was confirmed by
      impaired response to several pruritogens in dorsal root ganglia neurons excised
      from NC/Nga mice after termination of the studies. The response to the stimuli
      was also reduced by pre-incubation of sensory neurons from untreated BALB/c mice
      with 0.0001% HOCl. CONCLUSIONS AND CLINICAL RELEVANCE: These data indicate a
      direct reduction in sensory response by HOCl, leading to significantly reduced
      itch and inflammation in vivo.

PMID- 29028289
TI  - Early vs delayed closure of loop defunctioning ileostomy in patients undergoing
      distal colorectal resections: an integrated systematic review and meta-analysis
      of published randomized controlled trials.
AB  - AIMS: The objective of this study was to evaluate the surgical outcomes and
      feasibility of early loop defunctioning ileostomy closure, within 2 weeks of
      index surgery, in patients undergoing distal colorectal resection. METHODS: A
      systematic review of the literature on published randomized controlled trials
      reporting the feasibility and outcomes on early vs delayed closure of loop
      defunctioning ileostomy in patients undergoing distal colorectal resection using
      the principles of meta-analysis on RevMan 5.4 statistical software was
      undertaken. RESULTS: Four randomized, controlled trials on 446 patients
      evaluating the feasibility and outcomes on early vs delayed closure of loop
      defunctioning ileostomy in patients undergoing low colorectal resection were
      analysed. There were 176 patients in the early closure group and 270 patients in
      the delayed closure group. The risk of anastomotic leak [risk ratio 0.37 (CI:
      0.10-1.42), P = 0.15], anastomotic stenosis [risk ratio 4.79 (CI: 0.23-98.47), P
      = 0.31] and postoperative complications [risk ratio 0.75 (CI: 0.48-1.16), P =
      0.19] was similar in both groups. In addition, there was no significant
      difference between the groups with regard to the duration of operation
      [standardized mean difference -0.49 (CI: -01.09, -0.12), P = 0.12] and length of
      hospitalization [standardized mean difference -0.04 (CI: -0.25, -0.18), P =
      0.75]. CONCLUSIONS: Early closure of loop defunctioning ileostomy in patients
      undergoing distal colorectal resection is feasible with comparable outcomes to
      delayed closure.

PMID- 29028291
TI  - Reproductive biology of Aechmea bracteata (Sw.) Griseb. (Bromelioideae:
      Bromeliaceae).
AB  - Individuals of Aechmea bracteata show inflorescences with red scape bracts and
      odourless, yellow, tubular diurnal flowers, with closely arranged sexual organs,
      producing a large amount of fruits. In order to investigate the reproductive
      system of this species, a suite of characters was assessed: phenology, floral
      morphology and biology, nectar production dynamics, and fruit and seed production
      and germination, as a result of controlled pollination crosses. The study was
      conducted during two flowering seasons in wild populations in Yucatan, Mexico.
      Results suggest an annual flowering pattern with one flowering peak; flowers were
      diurnal, showing partial dichogamy (protandry)-herkogamy, anthers and stigma
      become mature before floral aperture, which could lead to self-pollination,
      nectar is produced during anthesis, varying in volume and total sugar
      concentration during the day; fruits and seeds were produced in all experimental
      crosses (cross-pollination, obligated cross-pollination, assisted and unassisted
      selfing, geitonogamy and apomixis), as well as high percentage seed germination.
      Several species of Aechmea are reportedly self-compatible and autogamous, as
      suggested by results of selfing and non-assisted selfing crosses, but these
      results are negated by the presence of apomixis, indicating that the species is
      apomictic. This is the first report of this breeding system for subgenus Aechmea
      and the sixth for Bromeliaceae. Polyembryony is here suggested for the first time
      in this genus and family based on the fact that more seeds were recorded that
      expected based on ovule numbers. Finally, when performing experimental crosses,
      estimating reproductive success based on number of seeds is a better approach
      than number of fruits, due to the effect of pseudogamy.

PMID- 29028290
TI  - Plasminogen activator inhibitor-1 regulates the vascular expression of
      vitronectin.
AB  - : Essentials Vitronectin (VN) is produced by smooth muscle cells (SMCs) and
      promotes neointima formation. We studied the regulation of vascular VN expression
      by plasminogen activator inhibitor-1 (PAI-1). PAI-1 stimulates VN gene expression
      in SMCs by binding LDL receptor-related protein 1. Stimulation of VN gene
      expression may be a mechanism by which PAI-1 controls vascular remodeling.
      SUMMARY: Background Increased expression of vitronectin (VN) by smooth muscle
      cells (SMCs) promotes neointima formation after vascular injury, and may
      contribute to chronic vascular diseases, such as atherosclerosis. However, the
      molecular regulation of vascular VN expression is poorly defined. Given the
      overlapping expression profiles and functions of VN and plasminogen activator
      inhibitor (PAI)-1, we hypothesized that PAI-1 regulates vascular VN expression.
      Objectives To determine whether PAI-1 regulates VN expression in SMCs and in
      vivo. Methods The effects of genetic alterations in PAI-1 expression,
      pharmacologic PAI-1 inhibition and recombinant PAI-1 on SMC VN expression were
      studied, and vascular VN expression in wild-type (WT) and PAI-1-deficient mice
      was assessed. Results VN expression was significantly lower in PAI-1-deficient
      SMCs and significantly increased in PAI-1-overexpressing SMCs. PAI-1 small
      interfering RNA and pharmacologic PAI-1 inhibition significantly decreased SMC VN
      expression. Recombinant PAI-1 stimulated VN expression by binding LDL receptor
      related protein-1 (LRP1), but another LRP1 ligand, alpha2 -macroglobulin, did
      not. As compared with WT controls, carotid artery VN expression was significantly
      lower in PAI-1-deficient mice and significantly higher in PAI-1-transgenic mice.
      In a vein graft (VG) model of intimal hyperplasia, VN expression was
      significantly attenuated in PAI-1-deficient VGs as compared with WT controls. The
      plasma VN concentration was significantly decreased in PAI-1-deficient mice
      versus WT controls at 4 weeks, but not at 5 days or 8 weeks, after surgery.
      Conclusions PAI-1 stimulates SMC VN expression by binding LRP1, and controls
      vascular VN expression in vivo. Autocrine regulation of vascular VN expression by
      PAI-1 may play important roles in vascular homeostasis and pathologic vascular
      remodeling.

PMID- 29028292
TI  - Dynamics of soil biogeochemical gas emissions shaped by remolded aggregate sizes
      and carbon configurations under hydration cycles.
AB  - Changes in soil hydration status affect microbial community dynamics and shape
      key biogeochemical processes. Evidence suggests that local anoxic conditions may
      persist and support anaerobic microbial activity in soil aggregates (or in
      similar hot spots) long after the bulk soil becomes aerated. To facilitate
      systematic studies of interactions among environmental factors with
      biogeochemical emissions of CO2 , N2 O and CH4 from soil aggregates, we remolded
      silt soil aggregates to different sizes and incorporated carbon at different
      configurations (core, mixed, no addition). Assemblies of remolded soil aggregates
      of three sizes (18, 12, and 6 mm) and equal volumetric proportions were embedded
      in sand columns at four distinct layers. The water table level in each column
      varied periodically while obtaining measurements of soil GHG emissions for the
      different aggregate carbon configurations. Experimental results illustrate that
      methane production required prolonged inundation and highly anoxic conditions for
      inducing measurable fluxes. The onset of unsaturated conditions (lowering water
      table) resulted in a decrease in CH4 emissions while temporarily increasing N2 O
      fluxes. Interestingly, N2 O fluxes were about 80% higher form aggregates with
      carbon placement in center (anoxic) core compared to mixed carbon within
      aggregates. The fluxes of CO2 were comparable for both scenarios of carbon
      sources. These experimental results highlight the importance of hydration
      dynamics in activating different GHG production and affecting various transport
      mechanisms about 80% of total methane emissions during lowering water table level
      are attributed to physical storage (rather than production), whereas CO2
      emissions (~80%) are attributed to biological activity. A biophysical model for
      microbial activity within soil aggregates and profiles provides a means for
      results interpretation and prediction of trends within natural soils under a wide
      range of conditions.

PMID- 29028293
TI  - A large case series on surgical outcomes in congenital factor XIII deficiency
      patients in Iran.
AB  - : Essentials Data on surgery in factor XIII (FXIII) deficiency patients are
      scarce and lack standardized guidelines. Variable dosage of 10-50 U kg-1 was
      given to FXIII deficiency patients undergoing surgery. Surgical outcomes showed
      excellent hemostasis with a minimal risk of post-operative complications. Surgery
      can be performed safely in FXIII deficiency patients following FXIII
      administration. SUMMARY: Background The lack of accepted standardized surgical
      guidelines leads to dependence on the treating physicians' and centers'
      experiences. Aim Our aim is to evaluate the surgical outcomes of a large group of
      congenital factor XIII deficiency (FXIIID) patients. Methods A case series study
      was conducted prior to surgery on congenital FXIIID patients in two major
      referral centers located in Iran from 2010 to 2016. All patients were on
      prophylaxis using plasma factor XIII concentrate (10 U kg-1 , every 28 days)
      except for three patients. Single doses of 10 U kg-1 or 30 U kg-1 plasma factor
      XIII concentrate were given before a minor procedure and circumcision,
      respectively. Two doses of plasma factor XIII concentrate, one 30 U kg-1 prior to
      the procedure and the second dose of 30 U kg-1 on postoperative day 3, were given
      for major surgery. The dose was 50 U kg-1 both before and after neurosurgical
      procedures. Results One hundred and sixty-two FXIIID patients underwent minor,
      major and obstetrical/gynecological surgeries. Median age of the patients was 14
      years (ages ranged 15 days to 47 years). The male-to-female ratio was 89/73. Five
      postoperative complications, two bleeding and three thrombosis, were recorded.
      Conclusion Our study showed excellent hemostasis in FXIIID patients undergoing
      surgeries. During the period of these surgeries, we observed only 1.8%
      postoperative complications. Surgery can be performed safely in FXIIID patients,
      and our proposed treatment regimens lead to adequate hemostatic coverage with
      minimal risk, for both minor and major surgeries.

PMID- 29028294
TI  - Carbon Dots/g-C3N4 Nanoheterostructures-Based Signal-Generation Tags for
      Photoelectrochemical Immunoassay of Cancer Biomarkers Coupling with Copper
      Nanoclusters.
AB  - A class of 0-dimensional/2-dimensional (0D/2D) nanoheterostructures based on
      carbon quantum dots (CQDs) and graphitic carbon nitride (g-C3N4) was designed as
      the signal-generation tags for the sensitive photoelectrochemical (PEC)
      immunoassay of prostate-specific antigen (PSA) coupling with the copper
      nanoclusters (CuNCs). Combination of CQDs with g-C3N4 promoted the photoexcited
      electron/hole separation and largely increased the photocurrents of the
      nanoheterostructures. Initially, a sandwich-type immunoreaction was carried out
      on monoclonal anti-PSA antibody-coated microplate by using PSA aptamer linked
      with CuNCs as the tracer. Accompanying the immunocomplex, the carried CuNCs were
      dissolved under acidic conditions. The as-released copper ions from the CuNCs
      could be captured onto the CQDs/g-C3N4 nanoheterostructures via the amino-group
      on the CQD surface as well as the -NHx (x = 1, 2, 3) of g-C3N4 nanosheets. The
      strong coordination of the Lewis basic sites on the CQDs/g-C3N4 with Cu2+
      decreased the photocurrent of the nanoheterostructures. Under optimal conditions,
      CQDs/g-C3N4 nanoheterostructures displayed good photocurrent responses for the
      detection of PSA within the dynamic linear range of 0.02-100 ng mL-1 and a limit
      of detection (LOD) of 5.0 pg mL-1. This method was also evaluated for
      quantitative screening of human PSA serum specimens by using the referenced
      electrochemiluminescent enzyme-linked immunoassay (ECL-ELIA) and gave good
      matched results between two methods. Additionally, this system was beneficial to
      explore the charge-separation and photoinduced electron transfer mechanism in the
      photoelectrochemical sensing protocols.

PMID- 29028295
TI  - Generation and Characterization of a meta-Aryne on Cu and NaCl Surfaces.
AB  - We describe the generation of a meta-aryne at low temperature (T = 5 K) using
      atomic manipulation on Cu(111) and on bilayer NaCl on Cu(111). We observe
      different voltage thresholds for dehalogenation of the precursor and different
      reaction products depending on the substrate surface. The chemical structure is
      resolved by atomic force microscopy with CO-terminated tips, revealing the
      radical positions and confirming a diradical rather than an anti-Bredt olefin
      structure for this meta-aryne on NaCl.

PMID- 29028296
TI  - Enhanced Flux and Electrochemical Cleaning of Silicate Scaling on Carbon Nanotube
      Coated Membrane Distillation Membranes Treating Geothermal Brines.
AB  - The desalination of inland brackish groundwater offers the opportunity to provide
      potable drinking water to residents and industrial cooling water to industries
      located in arid regions. Geothermal brines are used to generate electricity, but
      often contain high concentrations of dissolved salt. Here, we demonstrate how the
      residual heat left in spent geothermal brines can be used to drive a membrane
      distillation (MD) process and recover desalinated water. Porous polypropylene
      membranes were coated with a carbon nanotube (CNT)/poly(vinyl alcohol) layer,
      resulting in composite membranes having a binary structure that combines the
      hydrophobic properties critical for MD with the hydrophilic and conductive
      properties of the CNTs. We demonstrate that the addition of the CNT layer
      increases membrane flux due to enhanced heat transport from the bulk feed to the
      membrane surface, a result of CNT's high thermal transport properties.
      Furthermore, we show how hydroxide ion generation, driven by water electrolysis
      on the electrically conducting membrane surface, can be used to efficiently
      dissolve silicate scaling that developed during the process of desalinating the
      geothermal brine, negating the need for chemical cleaning.

PMID- 29028298
TI  - Ultrathin Nanocrystalline Diamond Films with Silicon Vacancy Color Centers via
      Seeding by 2 nm Detonation Nanodiamonds.
AB  - Color centers in diamonds have shown excellent potential for applications in
      quantum information processing, photonics, and biology. Here we report chemical
      vapor deposition (CVD) growth of nanocrystalline diamond (NCD) films as thin as 5
      6 nm with photoluminescence (PL) from silicon-vacancy (SiV) centers at 739 nm.
      Instead of conventional 4-6 nm detonation nanodiamonds (DNDs), we prepared and
      employed hydrogenated 2 nm DNDs (zeta potential = +36 mV) to form extremely dense
      (~1.3 * 1013 cm-2), thin (2 +/- 1 nm), and smooth (RMS roughness < 0.8 nm)
      nucleation layers on an Si/SiOx substrate, which enabled the CVD growth of such
      ultrathin NCD films in two different and complementary microwave (MW) CVD
      systems: (i) focused MW plasma with an ellipsoidal cavity resonator and (ii)
      pulsed MW plasma with a linear antenna arrangement. Analytical ultracentrifuge,
      infrared and Raman spectroscopies, atomic force microscopy, and scanning electron
      microscopy are used for detailed characterization of the 2 nm H-DNDs and the
      nucleation layer as well as the ultrathin NCD films. We also demonstrate on/off
      switching of the SiV center PL in the NCD films thinner than 10 nm, which is
      achieved by changing their surface chemistry.

PMID- 29028299
TI  - Environmental Engineering of Pd Nanoparticle Catalysts for Catalytic
      Hydrogenation of CO2 and Bicarbonate.
AB  - The extraordinary catalytic properties of enzymes are derived not only from their
      catalytic groups but also the unique properties of the active site. Tuning the
      microenvironment of synthetic catalysts is expected to enhance their performance
      if effective strategies can be developed. Interfacially cross-linked reverse
      micelles were prepared from three different cross-linkable surfactants. Pd
      nanoparticles were deposited in the core of the micelle for the catalytic
      hydrogenation of bicarbonate and CO2. The catalytic performance was found to
      depend heavily on the nature of the headgroup of the surfactant. Quaternary
      ammonium-based surfactants through ion exchange could bring bicarbonate to the
      catalytic center, whereas tertiary amine-based surfactants worked particularly
      well in CO2 hydrogenation, with turnover numbers an order of magnitude higher
      than that of commercially available Pd/C. The amines were proposed to bring CO2
      to the proximity of the catalysts through reversible formation of carbamate, in
      the nanospace of the hydrophilic core of the cross-linked reverse micelle. In the
      bicarbonate reduction, additional improvement of the catalysts was achieved
      through localized sol-gel synthesis that introduced metal oxide near the
      catalytic metal.

PMID- 29028300
TI  - Highly Efficient UV Protection of the Biomaterial Wood by A Transparent TiO2/Ce
      Xerogel.
AB  - Titanium dioxide is widely used in sunscreens because of its strong ultraviolet
      (UV) light absorbing capabilities and its resistance to discoloration under UV
      exposure. However, when deposited as a thin film, the high refractive index of
      titanium dioxide typically results in whiteness and opacity, which limits the use
      of titanium dioxide for material surfaces, for which long-term natural appearance
      is of high relevance. Since the whitish appearance is due to the strong light
      scattering and reflection on the interface of oxide particles and air, one can
      increase the transparency of TiO2 coatings by forming a continuous TiO2 layer.
      The purpose of the present article is 2-fold. First, we show that, in the
      presence of cerium ammonium nitrate, titanium dioxide can be turned from a white
      powder into a TiO2/Ce xerogel via a facile bottom-up fabrication process. Second,
      we demonstrate that the transparent TiO2/Ce xerogel can diminish surface
      deterioration induced by UV light and preserve the natural appearance of the
      highly abundant biomaterial wood. Furthermore, EPR spectroscopy revealed that the
      TiO2/Ce xerogel coating suppresses free radical generation on wood surfaces upon
      UV irradiation. Our research expands the applicability of the protective effect
      of titanium dioxide to coatings for natural engineering materials, which will
      become increasingly important in future bioeconomies.

PMID- 29028297
TI  - Spectroscopic Imaging at the Nanoscale: Technologies and Recent Applications.

PMID- 29028301
TI  - Metallic Cobalt@Nitrogen-Doped Carbon Nanocomposites: Carbon-Shell Regulation
      toward Efficient Bi-Functional Electrocatalysis.
AB  - To advance hydrogen economy, noble-metal-free electrocatalysts with good
      efficiency are urgently demanded. They can be developed from metal-organic
      frameworks (MOFs) with abundant structure-variety, in which a controlled
      pyrolysis is desired to rationalize nanostructure and maximize catalytic
      activity. Herein, the efficient regulation is proposed for the first time on the
      carbon-shell of MOFs-derived Co@NC nanocomposites via varying temperature and
      flow-rate during pyrolysis, enabling the good accessibility and the electronic
      optimization of active Co cores. With moderated temperature and flow-rate, the
      resulting ultrathin carbon-shell, on the one hand, renders Co cores easily
      accessible to electrolytes and, on the other hand, promotes the electronic
      penetration to optimize metallic Co active sites. As expected, the optimal Co@NC
      affords the benchmarking performance of noble-metal-free electrocatalysts in
      hydrogen evolution and oxygen reduction reactions, featured by the low
      overpotentials, the striking kinetic metrics, and the outstanding long-term
      stability. Elucidating the feasibility to design efficient electrocatalysts via
      controlled MOFs pyrolysis, this work will open up new opportunities for the
      development of cost-effective materials in the energy field.

PMID- 29028302
TI  - High Ion-Exchange Capacity Semihomogeneous Cation Exchange Membranes Prepared via
      a Novel Polymerization and Sulfonation Approach in Porous Polypropylene.
AB  - Semihomogeneous cation exchange membranes with superior ion exchange capacity
      (IEC) were synthesized via a novel polymerization and sulfonation approach in
      porous polypropylene support. The IEC of membranes could reach up to 3 mmol/g
      because of high mass ratio of functional polymer to membrane support. Especially,
      theoretical IEC threshold value agreed well with experimental threshold value,
      indicating that IEC could be specifically designed without carrying out extensive
      experiments. Also, sulfonate groups were distributed both on membrane surface and
      across the membranes, which corresponded well with high IEC of the synthesized
      membranes. In addition, the semifinished membrane showed hydrophobic property
      because of the formation of polystyrene. In contrast, the final membranes
      demonstrated super hydrophilic property, indicating the adequate sulfonation of
      polystyrene. Furthermore, when sulfonation reaction time increased, the
      conductivity of membranes also showed a tendency to increase, revealing the
      positive relationship between conductivity and IEC. Finally, the final membranes
      showed sufficient thermal stability for electrodialysis applications such as
      water desalination.

PMID- 29028304
TI  - Enhancing Efficiency of Perovskite Solar Cells via Surface Passivation with
      Graphene Oxide Interlayer.
AB  - Perovskite solar cells have been demonstrated as promising low-cost and highly
      efficient next-generation solar cells. Enhancing VOC by minimization the
      interfacial recombination kinetics can further improve device performance. In
      this work, we for the first time reported on surface passivation of perovskite
      layers with chemical modified graphene oxides, which act as efficient interlayer
      to reduce interfacial recombination and enhance hole extraction as well. Our
      modeling points out that the passivation effect mainly comes from the interaction
      between functional group (4-fluorophenyl) and under-coordinated Pb ions. The
      resulting perovskite solar cells achieved high efficient power conversion
      efficiency of 18.75% with enhanced high open circuit VOC of 1.11 V. Ultrafast
      spectroscopy, photovoltage/photocurrent transient decay, and electronic impedance
      spectroscopy characterizations reveal the effective passivation effect and the
      energy loss mechanism. This work sheds light on the importance of interfacial
      engineering on the surface of perovskite layers and provides possible ways to
      improve device efficiency.

PMID- 29028305
TI  - Fast Image-Guided Stratification Using Anti-Programmed Death Ligand 1 Gold
      Nanoparticles for Cancer Immunotherapy.
AB  - Cancer immunotherapy has made enormous progress in offering safer and more
      effective treatments for the disease. Specifically, programmed death ligand 1
      antibody (alphaPDL1), designed to perform immune checkpoint blockade (ICB), is
      now considered a pillar in cancer immunotherapy. However, due to the complexity
      and heterogeneity of tumors, as well as the diversity in patient response, ICB
      therapy only has a 30% success rate, at most; moreover, the efficacy of ICB can
      be evaluated only two months after start of treatment. Therefore, early
      identification of potential responders and nonresponders to therapy, using
      noninvasive means, is crucial for improving treatment decisions. Here, we report
      a straightforward approach for fast, image-guided prediction of therapeutic
      response to ICB. In a colon cancer mouse model, we demonstrate that the
      combination of computed tomography imaging and gold nanoparticles conjugated to
      alphaPDL1 allowed prediction of therapeutic response, as early as 48 h after
      treatment. This was achieved by noninvasive measurement of nanoparticle
      accumulation levels within the tumors. Moreover, we show that the nanoparticles
      efficiently prevented tumor growth with only a fifth of the standard dosage of
      clinical care. This technology may be developed into a powerful tool for early
      and noninvasive patient stratification as responders or nonresponders.

PMID- 29028303
TI  - Neutrophil-Particle Interactions in Blood Circulation Drive Particle Clearance
      and Alter Neutrophil Responses in Acute Inflammation.
AB  - Although nano- and microparticle therapeutics have been studied for a range of
      drug delivery applications, the presence of these particles in blood flow may
      have considerable and understudied consequences to circulating leukocytes,
      especially neutrophils, which are the largest human leukocyte population. The
      objective of this work was to establish if particulate drug carriers in
      circulation interfere with normal neutrophil adhesion and migration. Circulating
      blood neutrophils in vivo were found to be capable of rapidly binding and
      sequestering injected carboxylate-modified particles of both 2 and 0.5 MUm
      diameter within the bloodstream. These neutrophil-particle associations within
      the vasculature were found to suppress neutrophil interactions with an inflamed
      mesentery vascular wall and hindered neutrophil adhesion. Furthermore, in a model
      of acute lung injury, intravenously administered drug-free particles reduced
      normal neutrophil accumulation in the airways of C57BL/6 mice between 52% and 60%
      versus particle-free mice and between 93% and 98% in BALB/c mice. This suppressed
      neutrophil migration resulted from particle-induced neutrophil diversion to the
      liver. These data indicate a considerable acute interaction between injected
      particles and circulating neutrophils that can drive variations in neutrophil
      function during inflammation and implicate neutrophil involvement in the
      clearance process of intravenously injected particle therapeutics. Such an
      understanding will be critical toward both enhancing designs of drug delivery
      carriers and developing effective therapeutic interventions in diseases where
      neutrophils have been implicated.

PMID- 29028306
TI  - Wet Spinning of Flame-Retardant Cellulosic Fibers Supported by Interfacial
      Complexation of Cellulose Nanofibrils with Silica Nanoparticles.
AB  - The inherent flammability of cellulosic fibers limits their use in some advanced
      applications. This work demonstrates for the first time the production of flame
      retardant macroscopic fibers from wood-derived cellulose nanofibrils (CNF) and
      silica nanoparticles (SNP). The fibers are made by extrusion of aqueous
      suspensions of anionic CNF into a coagulation bath of cationic SNP at an acidic
      pH. As a result, the fibers with a CNF core and a SNP thin shell are produced
      through interfacial complexation. Silica-modified nanocellulose fibers with a
      diameter of ca. 15 MUm, a titer of ca. 3 dtex and a tenacity of ca. 13 cN tex-1
      are shown. The flame retardancy of the fibers is demonstrated, which is
      attributed to the capacity of SNP to promote char forming and heat insulation on
      the fiber surface.

PMID- 29028307
TI  - Metabolomics of Small Numbers of Cells: Metabolomic Profiling of 100, 1000, and
      10000 Human Breast Cancer Cells.
AB  - In cellular metabolomics, it is desirable to carry out metabolomic profiling
      using a small number of cells in order to save time and cost. In some
      applications (e.g., working with circulating tumor cells in blood), only a
      limited number of cells are available for analysis. In this report, we describe a
      method based on high-performance chemical isotope labeling (CIL) nanoflow liquid
      chromatography mass spectrometry (nanoLC-MS) for high-coverage metabolomic
      analysis of small numbers of cells (i.e., <=10000 cells). As an example, 12C-/13C
      dansyl labeling of the metabolites in lysates of 100, 1000, and 10000 MCF-7
      breast cancer cells was carried out using a new labeling protocol tailored to
      handle small amounts of metabolites. Chemical-vapor-assisted ionization in a
      captivespray interface was optimized for improving metabolite ionization and
      increasing robustness of nanoLC-MS. Compared to microflow LC-MS, the nanoflow
      system provided much improved metabolite detectability with a significantly
      reduced sample amount required for analysis. Experimental duplicate analyses of
      biological triplicates resulted in the detection of 1620 +/- 148, 2091 +/- 89 and
      2402 +/- 80 (n = 6) peak pairs or metabolites in the amine/phenol submetabolome
      from the 12C-/13C-dansyl labeled lysates of 100, 1000, and 10000 cells,
      respectively. About 63-69% of these peak pairs could be either identified using
      dansyl labeled standard library or mass-matched to chemical structures in human
      metabolome databases. We envisage the routine applications of this method for
      high-coverage quantitative cellular metabolomics using a starting material of
      10000 cells. Even for analyzing 100 or 1000 cells, although the metabolomic
      coverage is reduced from the maximal coverage, this method can still detect
      thousands of metabolites, allowing the analysis of a large fraction of the
      metabolome and focused analysis of the detectable metabolites.

PMID- 29028308
TI  - Topographical Manipulation of Microparticles and Cells with Acoustic
      Microstreaming.
AB  - Precise and reproducible manipulation of synthetic and biological microscale
      objects in complex environments is essential for many practical biochip and
      microfluidic applications. Here, we present an attractive acoustic topographical
      manipulation (ATM) method to achieve efficient and reproducible manipulation of
      diverse microscale objects. This new guidance method relies on the acoustically
      induced localized microstreaming forces generated around microstructures, which
      are capable of trapping nearby microobjects and manipulating them along a
      determined trajectory based on local topographic features. This unique phenomenon
      is investigated by numerical simulations examining the local microstreaming in
      the presence of microscale boundaries under the standing acoustic wave. This
      method can be used to manipulate a single microobject around a complex structure
      as well as collectively manipulate multiple objects moving synchronously along
      complicated shapes. Furthermore, the ATM can serve for automated maze solving by
      autonomously manipulating microparticles with diverse geometries and densities,
      including live cells, through complex maze-like topographical features without
      external feedback, particle modification, or adjustment of operational
      parameters.

PMID- 29028309
TI  - Unique Reversible Conversion-Type Mechanism Enhanced Cathode Performance in
      Amorphous Molybdenum Polysulfide.
AB  - A unique reversible conversion-type mechanism is reported in the amorphous
      molybdenum polysulfide (a-MoS5.7) cathode material. The lithiation products of
      metallic Mo and Li2S2 rather than Mo and Li2S species have been detected. This
      process could yield a high discharge capacity of 746 mAh g-1. Characterizations
      of the recovered molybdenum polysulfide after the delithiaiton process manifests
      the high reversibility of the unique conversion reaction, in contrast with the
      general irreversibility of the conventional conversion-type mechanism. As a
      result, the a-MoS5.7 electrodes deliver high cycling stability with an energy
      density retention of 1166 Wh kg-1 after 100 cycles. These results provide a novel
      model for the design of high-capacity and long-life electrode materials.

PMID- 29028310
TI  - Direct Observation of Oxygen Vacancy Distribution across Yttria-Stabilized
      Zirconia Grain Boundaries.
AB  - Crystalline interfaces in materials often govern the macroscopic functional
      properties owing to their complex structure and chemical inhomogeneity. For ionic
      crystals, however, such understanding has been precluded by the debatable local
      anion distribution across crystal interfaces. In this study, using yttria
      stabilized zirconia as a model material, the oxygen vacancy distribution across
      individual grain boundaries was directly quantified by atomic-resolution scanning
      transmission electron microscopy with ultrahigh-sensitive energy-dispersive X-ray
      spectroscopy. Combined with dynamical scattering calculations, we unambiguously
      show that the relative oxygen concentrations increase in four high-angle grain
      boundaries, indicating that the oxygen vacancies are actually depleted near the
      grain boundary cores. These results experimentally evidence that the long-range
      electric interaction is the dominant factor to determine the local point defect
      distribution at ionic crystal interfaces.

PMID- 29028312
TI  - Light-Gated Memristor with Integrated Logic and Memory Functions.
AB  - Memristive devices are able to store and process information, which offers
      several key advantages over the transistor-based architectures. However, most of
      the two-terminal memristive devices have fixed functions once made and cannot be
      reconfigured for other situations. Here, we propose and demonstrate a memristive
      device "memlogic" (memory logic) as a nonvolatile switch of logic operations
      integrated with memory function in a single light-gated memristor. Based on
      nonvolatile light-modulated memristive switching behavior, a single memlogic cell
      is able to achieve optical and electrical mixed basic Boolean logic of
      reconfigurable "AND", "OR", and "NOT" operations. Furthermore, the single
      memlogic cell is also capable of functioning as an optical adder and digital-to
      analog converter. All the memlogic outputs are memristive for in situ data
      storage due to the nonvolatile resistive switching and persistent
      photoconductivity effects. Thus, as a memdevice, the memlogic has potential for
      not only simplifying the programmable logic circuits but also building memristive
      multifunctional optoelectronics.

PMID- 29028311
TI  - Radiolabeled, Antibody-Conjugated Manganese Oxide Nanoparticles for Tumor
      Vasculature Targeted Positron Emission Tomography and Magnetic Resonance Imaging.
AB  - Manganese oxide nanoparticles (Mn3O4 NPs) have attracted a great deal of
      attention in the field of biomedical imaging because of their ability to create
      an enhanced imaging signal in MRI as novel potent T1 contrast agents. In this
      study, we present tumor vasculature-targeted imaging in mice using Mn3O4 NPs
      through conjugation to the anti-CD105 antibody TRC105 and radionuclide copper-64
      (64Cu, t1/2: 12.7 h). The Mn3O4 conjugated NPs, 64Cu-NOTA-Mn3O4@PEG-TRC105,
      exhibited sufficient stability in vitro and in vivo. Serial positron emission
      tomography (PET) and magnetic resonance imaging (MRI) studies evaluated the
      pharmacokinetics and demonstrated targeting of 64Cu-NOTA-Mn3O4@PEG-TRC105 to 4T1
      murine breast tumors in vivo, compared to 64Cu-NOTA-Mn3O4@PEG. The specificity of
      64Cu-NOTA-Mn3O4@PEG-TRC105 for the vascular marker CD105 was confirmed through in
      vivo, in vitro, and ex vivo experiments. Since Mn3O4 conjugated NPs exhibited
      desirable properties for T1 enhanced imaging and low toxicity, the tumor-specific
      Mn3O4 conjugated NPs reported in this study may serve as promising
      multifunctional nanoplatforms for precise cancer imaging and diagnosis.

PMID- 29028313
TI  - Anomalous Corrosion of Bulk Transition Metal Diselenides Leading to Stable
      Monolayers.
AB  - In this paper we provide insight into an anomalous corrosion process, referred to
      as electroablation (EA), which converts multilayer flakes of transition metal
      diselenides like MoSe2 into their corresponding monolayers when micromechanically
      exfoliated on a conductive electrode and subsequently subjected to a high anodic
      potential inside a conventional electrochemical cell. Photoluminescence intensity
      maps and scanning transmission electron microscopy (STEM) images confirmed the
      single crystalline nature and 2H-hexagonal lattice structure of the remnant
      monolayer MoSe2 flakes, indicating the superior corrosion stability of the
      monolayers compared to that of the bulk counterpart. It is noted that the EA
      technique is a low-cost alternative for high-yield synthesis of single
      crystalline monolayer MoSe2 at room temperature. We also found that the dynamics
      of such an electro-oxidation-mediated and self-limiting corrosion process differs
      significantly for MoSe2 and WSe2. While we were able to engineer the corrosion
      conditions for the EA process to obtain monolayers of MoSe2, our attempts to
      obtain monolayers of WSe2 were largely unsuccessful. Finally, we constructed a
      phenomenological physical chemistry framework to explain such anomalous corrosion
      processes in transition metal diselenides.

PMID- 29028314
TI  - Heterologous Gene Expression of N-Terminally Truncated Variants of LipPks1
      Suggests a Functionally Critical Structural Motif in the N-terminus of Modular
      Polyketide Synthase.
AB  - Streptomyces genomes have a high G + C content and typically use an ATG or GTG
      codon to initiate protein synthesis. Although gene-finding tools perform well in
      low GC genomes, it is known that the accuracy in predicting a translational start
      site (TSS) is much less for high GC genomes. LipPks1 is a Streptomyces-derived,
      well-characterized modular polyketide synthase (PKS). Using this enzyme as a
      model, we experimentally investigated the effects of alternative TSSs using a
      heterologous host, Streptomyces venezuelae. One of the TSSs employed boosted the
      protein level by 59-fold and the product yield by 23-fold compared to the
      originally annotated start codon. Interestingly, a structural model of the PKS
      indicated the presence of a structural motif in the N-terminus, which may explain
      the observed different protein levels together with a proline and arginine-rich
      sequence that may inhibit translational initiation. This structure was also found
      in six other modular PKSs that utilize noncarboxylated starter substrates, which
      may guide the selection of optimal TSSs in conjunction with start-codon
      prediction software.

PMID- 29028315
TI  - Nanoparticles of Short Cationic Peptidopolysaccharide Self-Assembled by Hydrogen
      Bonding with Antibacterial Effect against Multidrug-Resistant Bacteria.
AB  - Cationic antimicrobial peptides (AMPs) and polymers are active against many
      multidrug-resistant (MDR) bacteria, but only a limited number of these compounds
      are in clinical use due to their unselective toxicity. The typical strategy for
      achieving selective antibacterial efficacy with low mammalian cell toxicity is
      through balancing the ratio of cationicity to hydrophobicity. Herein, we report a
      cationic nanoparticle self-assembled from chitosan-graft-oligolysine (CSM5-K5)
      chains with ultralow molecular weight (1450 Da) that selectively kills bacteria.
      Further, hydrogen bonding rather than the typical hydrophobic interaction causes
      the polymer chains to be aggregated together in water into small nanoparticles
      (with about 37 nm hydrodynamic radius) to concentrate the cationic charge of the
      lysine. When complexed with bacterial membrane, these cationic nanoparticles
      synergistically cluster anionic membrane lipids and produce a greater membrane
      perturbation and antibacterial effect than would be achievable by the same
      quantity of charge if dispersed in individual copolymer molecules in solution.
      The small zeta potential (+15 mV) and lack of hydrophobicity of the nanoparticles
      impedes the insertion of the copolymer into the cell bilayer to improve
      biocompatibility. In vivo study (using a murine excisional wound model) shows
      that CSM5-K5 suppresses the growth of methicillin-resistant Staphylococcus aureus
      (MRSA) bacteria by 4.0 orders of magnitude, an efficacy comparable to that of the
      last resort MRSA antibiotic vancomycin; it is also noninflammatory with little/no
      activation of neutrophils (CD11b and Ly6G immune cells). This study demonstrates
      a promising new class of cationic polymers-short cationic peptidopolysaccharides
      that effectively attack MDR bacteria due to the synergistic clustering of, rather
      than insertion into, bacterial anionic lipids by the concentrated polymers in the
      resulting hydrogen-bonding-stabilized cationic nanoparticles.

PMID- 29028316
TI  - Tailoring Nanocrystalline Metal-Organic Frameworks as Fluorescent Dye Carriers
      for Bioimaging.
AB  - Challenges exist in taking advantage of dye molecules for reliable and
      reproducible molecular probes in biomedical applications. In this study, we show
      how to utilize the dye molecules for bioimaging within protective carriers of
      nanocrystalline metal-organic frameworks (nMOFs) particles. Specifically,
      Resorufin and Rhodamine-6G having different molecular sizes were encapsulated
      within close-fitting pores of nMOF-801 and nUiO-67 particles, respectively. The
      resulting nanocrystalline particles have high crystallinity, uniform size, and
      morphology and preserve enhanced photoluminescence properties with exceptional
      stabilities in biomedical environment. The samples are further functionalized
      with a targeting agent and successfully work for fluorescence imaging of FL83B
      (human hepatocyte cell) and HepG2 (human hepatocellular carcinoma) without
      cytotoxicity.

PMID- 29028317
TI  - Impacts of Near-Future Ocean Acidification and Warming on the Shell Mechanical
      and Geochemical Properties of Gastropods from Intertidal to Subtidal Zones.
AB  - Many marine organisms produce calcareous shells as the key structure for defense,
      but the functionality of shells may be compromised by ocean acidification and
      warming. Nevertheless, calcifying organisms may adaptively modify their shell
      properties in response to these impacts. Here, we examined how reduced pH and
      elevated temperature affect shell mechanical and geochemical properties of common
      grazing gastropods from intertidal to subtidal zones. Given the greater
      environmental fluctuations in the intertidal zone, we hypothesized that
      intertidal gastropods would exhibit more plastic responses in shell properties
      than subtidal gastropods. Overall, three out of five subtidal gastropods produced
      softer shells at elevated temperature, while intertidal gastropods maintained
      their shell hardness at both elevated pCO2 (i.e., reduced pH) and temperature.
      Regardless of pH and temperature, degree of crystallization was maintained
      (except one subtidal gastropod) and carbonate polymorph remained unchanged in all
      tested species. One intertidal gastropod produced less soluble shells (e.g.,
      higher calcite/aragonite) in response to reduced pH. In contrast, subtidal
      gastropods produced only aragonite which has higher solubility than calcite.
      Overall, subtidal gastropods are expected to be more susceptible than intertidal
      gastropods to shell dissolution and physical damage under future seawater
      conditions. The increased vulnerability to shell dissolution and predation could
      have serious repercussions for their survival and ecological contributions in the
      future subtidal environment.

PMID- 29028319
TI  - Hop to It.

PMID- 29028320
TI  - Tunneling Control of Chemical Reactions: The Third Reactivity Paradigm.
AB  - This Perspective describes the emergence of tunneling control as a new reactivity
      paradigm in chemistry. The term denotes a tunneling reaction that passes through
      a high but narrow potential energy barrier, leading to formation of a product
      that would be disfavored if the reaction proceeded by passage over kinetic
      barriers rather than through them. This reactivity paradigm should be considered
      along with thermodynamic and kinetic control as a factor that can determine which
      of two or more possible products is likely to be the one obtained. Tunneling
      control is a concept that can provide a deep and detailed understanding of a
      variety of reactions that undergo facile (and possibly unrecognized) tunneling.

PMID- 29028318
TI  - Combination of Calpha-H Hydrogen Bonds and van der Waals Packing Modulates the
      Stability of GxxxG-Mediated Dimers in Membranes.
AB  - The GxxxG motif is frequently found at the dimerization interface of a
      transmembrane structural motif called GASright, which is characterized by a short
      interhelical distance and a right-handed crossing angle between the helices. In
      GASright dimers, such as glycophorin A (GpA), BNIP3, and members of the ErbB
      family, the backbones of the helices are in contact, and they invariably display
      networks of 4 to 8 weak hydrogen bonds between Calpha-H carbon donors and
      carbonyl acceptors on opposing helices (Calpha-H...O?C hydrogen bonds). These
      networks of weak hydrogen bonds at the helix-helix interface are presumably
      stabilizing, but their energetic contribution to dimerization has yet to be
      determined experimentally. Here, we present a computational and experimental
      structure-based analysis of GASright dimers of different predicted stabilities,
      which show that a combination of van der Waals packing and Calpha-H hydrogen
      bonding predicts the experimental trend of dimerization propensities. This
      finding provides experimental support for the hypothesis that the networks of
      Calpha-H hydrogen bonds are major contributors to the free energy of association
      of GxxxG-mediated dimers. The structural comparison between groups of GASright
      dimers of different stabilities reveals distinct sequence as well as
      conformational preferences. Stability correlates with shorter interhelical
      distances, narrower crossing angles, better packing, and the formation of larger
      networks of Calpha-H hydrogen bonds. The identification of these structural rules
      provides insight on how nature could modulate stability in GASright and finely
      tune dimerization to support biological function.

PMID- 29028321
TI  - Stereospecific Allylic Functionalization: The Reactions of Allylboronate
      Complexes with Electrophiles.
AB  - Allylboronic esters react readily with carbonyls and imines (pi-electrophiles),
      but are unreactive toward a range of other electrophiles. By addition of an
      aryllithium, the corresponding allylboronate complexes display enhanced
      nucleophilicity, enabling addition to a range of electrophiles (tropylium,
      benzodithiolylium, activated pyridines, Eschenmoser's salt, Togni's reagent,
      Selectfluor, diisopropyl azodicarboxylate (DIAD), MeSX) in high regio- and
      stereocontrol. This protocol provides access to key new functionalities,
      including quaternary stereogenic centers bearing moieties such as fluorine and
      the trifluoromethyl group. The allylboronate complexes were determined to be 7 to
      10 orders of magnitude more reactive than the parent boronic ester.

PMID- 29028322
TI  - Synthesis, Characterization, and Properties of Iron(II) Spin-Crossover Molecular
      Photoswitches Functioning at Room Temperature.
AB  - Spin-crossover molecular switches [FeII(H2B(pz)2)2L] (L = novel phenanthroline
      based ligands featuring photochromic diarylethene units; pz = 1-pyrazolyl) were
      synthesized and thoroughly characterized by variable-temperature X-ray
      crystallography, Mossbauer spectroscopy, and magnetic measurements. The effect of
      substituents introduced into the phenanthroline backbone (L2) and into the
      photochromic diarylethene unit (L3) on photophysical properties of metal-free
      ligands and spin-crossover iron(II) complexes 2 and 3, respectively, were
      investigated in detail. Both ligands and complexes could be switched with light
      in solution at room temperature. The photocyclization of 2 was accompanied by a
      high-spin to low-spin photoconversion determined at 19%. The closed-ring isomers
      of L3 and 3 reveal the lifetimes in the range of minutes, whereas those of L2 and
      2 are thermally stable for days in solutions at room temperature. The
      reversibility of the photoswitching can be improved by avoiding the
      photostationary states. Prospective introduction of anchoring groups to the
      phenanthroline backbone might allow the construction of chemisorbed self
      assembled monolayers of spin-crossover species switchable with light at room
      temperature.

PMID- 29028323
TI  - Benchmarking of Computational Methods for Creation of Retention Models in
      Quantitative Structure-Retention Relationships Studies.
AB  - Quantitative structure-retention relationship (QSRR) models are powerful
      techniques for the prediction of retention times of analytes, where
      chromatographic retention parameters are correlated with molecular descriptors
      encoding chemical structures of analytes. Many QSRR models contain geometrical
      descriptors derived from the three-dimensional (3D) spatial coordinates of
      computationally predicted structures for the analytes. Therefore, it is sensible
      to calculate these structures correctly, as any error is likely to carry over to
      the resulting QSRR models. This study compares molecular modeling, semiempirical,
      and density functional methods (both B3LYP and M06) for structure optimization.
      Each of the calculations was performed in a vacuum, then repeated with solvent
      corrections for both acetonitrile and water. We also compared Natural Bond
      Orbital analysis with the Mulliken charge calculation method. The comparison of
      the examined computational methods for structure calculation shows that, possibly
      due to the error inherent in descriptor creation methods, a quick and inexpensive
      molecular modeling method of structure determination gives similar results to
      experiments where structures are optimized using an expensive and time-consuming
      level of computational theory. Also, for structures with low flexibility, vacuum
      or gas phase calculations are found to be as effective as those calculations with
      solvent corrections added.

PMID- 29028324
TI  - Correction to Characterization of the Fleeting Hydroxoiron(III) Complex of the
      Pentadentate TMC-py Ligand.

PMID- 29028326
TI  - Ratiometric pH Imaging with a CoII2 MRI Probe via CEST Effects of Opposing pH
      Dependences.
AB  - We report a Co2-based magnetic resonance (MR) probe that enables the ratiometric
      quantitation and imaging of pH through chemical exchange saturation transfer
      (CEST). This approach is illustrated in a series of air- and water-stable CoII2
      complexes featuring CEST-active tetra(carboxamide) and/or hydroxyl-substituted
      bisphosphonate ligands. For the complex bearing both ligands, variable-pH CEST
      and NMR analyses reveal highly shifted carboxamide and hydroxyl peaks with
      intensities that increase and decrease with increasing pH, respectively. The
      ratios of CEST peak intensities at 104 and 64 ppm are correlated with solution pH
      in the physiological range 6.5-7.6 to construct a linear calibration curve of
      log(CEST104 ppm/CEST64 ppm) versus pH, which exhibits a remarkably high pH
      sensitivity of 0.99(7) pH unit-1 at 37  degrees C. In contrast, the analogous
      CoII2 complex with a CEST-inactive bisphosphonate ligand exhibits no such pH
      response, confirming that the pH sensitivity stems from the integration of amide
      and hydroxyl CEST effects that show base- and acid-catalyzed proton exchange,
      respectively. Importantly, the pH calibration curve is independent of the probe
      concentration and is identical in aqueous buffer and fetal bovine serum.
      Furthermore, phantom images reveal analogous linear pH behavior. The CoII2 probe
      is stable toward millimolar concentrations of H2PO4-/HPO42-, CO32-, SO42-, CH3COO
      , and Ca2+ ions, and more than 50% of melanoma cells remain viable in the
      presence of millimolar concentrations of the complex. The stability of the probe
      in physiological environments suggests that it may be suitable for in vivo
      studies. Together, these results highlight the ability of dinuclear transition
      metal PARACEST probes to provide a concentration-independent measure of pH, and
      they provide a potential design strategy toward the development of MR probes for
      ratiometric pH imaging.

PMID- 29028327
TI  - Carbon and Phosphorus Removal from Primary Municipal Wastewater Using Recovered
      Aluminum.
AB  - In this work, recovery of aluminum from coagulated primary sludge and its reuse
      potential as secondary coagulant were investigated. The recovery process
      consisted of releasing the particle-bound aluminum from primary sludge by
      acidification (HCl or H2SO4), followed by separation using centrifugation for
      dissolved coagulant recovery. The recovered coagulant was then reused for
      treating primary wastewater and overall coagulation efficiency was determined.
      While with fresh alum, the removal efficiencies of total suspended solids,
      chemical oxygen demand, total phosphorus, and total nitrogen were 85%, 65%, 80%
      and 33%, respectively, a drop in removal efficiency of total suspended solids and
      chemical oxygen demand was observed for recovered aluminum (85-60% and 65-50%,
      respectively). Nitrogen concentration remained almost constant with each cycle,
      while phosphorus in the effluent increased by 1 mg/L and 3 mg/L in the first and
      second cycle, respectively. Precipitation of various aluminum species was modeled
      for determining the recovery potential of aluminum at low pH. Preliminary cost
      analysis indicates that optimum recovery of aluminum occurred at a pH of 1.5 for
      both acids. Struvite precipitation effectively removed increased phosphorus
      solubilized by acidification at the end of second cycle, however, it also
      decreased the amount of aluminum available for recycle.

PMID- 29028325
TI  - DNA Aptamer-Based Activatable Probes for Photoacoustic Imaging in Living Mice.
AB  - DNA aptamers are a powerful class of molecules for sensing targets, but have been
      limited when applied to imaging in living animals because most aptamer probes are
      fluorescence-based, which limits imaging penetration depth. Photoacoustic (PA)
      imaging emerged as an alternative to MRI and X-ray tomography in biomedical
      imaging, due to its ability to afford high-resolution images at depths in the cm
      range. Despite its promise, PA imaging is limited by a lack of strategies to
      design selective and activatable probes for targets. To overcome this limitation,
      we report design and demonstration of PA probes based on DNA aptamers that can
      hybridize to DNA strands conjugated to a near-infrared fluorophore/quencher pair
      (IRDye 800CW/IRDye QC-1) with efficient contact quenching. Binding of the target
      triggered a release of the DNA strand with the quencher and thus relief of the
      contact quenching, resulting in a change of the PA signal ratio at 780/725 nm.
      Using thrombin as a model, a relationship was established between the thrombin
      concentrations and the PA ratio, with a dynamic range of 0-1000 nM and a limit of
      detection of 112 nM. Finally, in vivo PA imaging studies showed that the PA ratio
      increased significantly 45 min after injection of thrombin but not with injection
      of PBS as a vehicle control, demonstrating the first aptamer-based activatable PA
      probe for advanced molecular imaging in living mice. Since in vitro selection can
      obtain aptamers selective for many targets, the design demonstrated can be
      applied for PA imaging of a number of targets.

PMID- 29028328
TI  - Using Covalent Labeling and Mass Spectrometry To Study Protein Binding Sites of
      Amyloid Inhibiting Molecules.
AB  - Amyloid aggregates are associated with several debilitating diseases, and there
      are numerous efforts to develop small molecule treatments against these diseases.
      One challenge associated with these efforts is determining protein binding site
      information for potential therapeutics because amyloid-forming proteins rapidly
      form oligomers and aggregates, making traditional protein structural analysis
      techniques challenging. Using beta-2-microglobulin (beta2m) as a model amyloid
      forming protein along with two recently identified small molecule amyloid
      inhibitors (i.e., rifamycin SV and doxycycline), we demonstrate that covalent
      labeling and mass spectrometry (MS) can be used to map small-molecule binding
      sites for a rapidly aggregating protein. Specifically, three different covalent
      labeling reagents, namely diethylpyrocarbonate, 2,3-butanedione, and the reagent
      pair EDC/GEE, are used together to pinpoint the binding sites of rifamycin SV,
      doxycycline, and another molecule, suramin, which binds but does not inhibit
      Cu(II)-induced beta2m amyloid formation. The labeling results reveal binding
      sites that are consistent with the known effects of these molecules on beta2m
      amyloid formation and are in general agreement with molecular docking results. We
      expect that this combined covalent labeling approach will be applicable to other
      protein/small molecule systems that are difficult to study by traditional means.

PMID- 29028329
TI  - Sponge Spray-Reaching New Dimensions of Direct Sampling and Analysis by MS.
AB  - Sample preparation for the analysis of clinical samples with the mass
      spectrometer (MS) can be extensive and expensive. Simplifying and speeding up the
      process would be very beneficial. This paper reports sponge spray-a novel
      sampling and direct MS analysis approach-attempting exactly that. It enables
      direct analysis without any sample preparation from dried blood, plasma, and
      urine. The tip of a volumetric absorptive microsampling device is used to collect
      an exact amount of sample and from that same tip an electrospray can be directed
      into a mass spectrometer. We demonstrate here that, although with significant
      matrix effects, quantitation of penicillin G, a common antimicrobial, is possible
      in plasma and in urine, with essentially no sample preparation.

PMID- 29028330
TI  - Ambient-Stable Bis-Azoaromatic-Centered Diradical [(L*)M(L*)] Complexes of
      Rh(III): Synthesis, Structure, Redox, and Spin-Spin Interaction.
AB  - Bis-azoaromatic electron traps, viz. 2-(2-pyridylazo)azoarene 1, have been
      synthesized by colligating electron-deficient pyridine and azoarene moieties, and
      they act as apposite proradical templates for the formation of stable open-shell
      diradical complexes [(1*-)RhIII(1*-)]+ ([2]+), starting from the low-valent
      electron reservoir [RhI]. The less stable monoradical [RhIII(1*-)Cl2(PPh3)3] (3)
      has also been isolated as a minor product. These pi-radical complexes are
      multiredox systems, and the electron transfer processes occur exclusively within
      the pincer-type NNN ligand backbone 1. Molecular and electronic structures of the
      diradicals and monoradicals have been ascertained with the aid of X-ray
      diffraction, electrochemical, spectroelectrochemical, and spectral (electronic,
      IR, NMR, and EPR) studies. In the diradicals [2]+, the orthogonal disposition of
      two ligand pi orbitals linked via a closed-shell metal center (t26) impedes
      significant coupling between the radicals. Indeed, the observed magnetic moment
      of [2a]+ lies near ~2.3 MUB over the temperature range 50-300 K. A very weak
      antiferromagnetic (AF) intramolecular spin-spin interaction between two ligand pi
      arrays in [(1*-)RhIII(1*-)]+ have been found experimentally (J ~ -5 cm-1), and
      this is further substantiated by density functional theory (DFT) calculations at
      the (U)B3LYP/6-31G(d,p) level.

PMID- 29028331
TI  - Ion-Induced Hydrogel Formation and Nematic Ordering of Nanocrystalline Cellulose
      Suspensions.
AB  - Nanocrystalline cellulose (NCC) is a promising material for formation of
      hydrogels and nematic liquid crystals. While salt addition is known to facilitate
      hydrogel formation, it remains unclear whether this originates from cationic
      bridging or charge screening effects. Herein, we demonstrate the effect of mono-
      and divalent salts on NCC gelation and nematic ordering. A strong correlation of
      NCC suspension zeta-potential and rheological behavior was found. Lower
      concentrations of divalent cations were needed to decrease NCC zeta-potential and
      form hydrogels. The same zeta-potentials and gel strengths were achieved at
      higher concentrations of monovalent salts. Salt-induced NCC aggregation is thus
      caused by intermolecular attractive forces rather than cationic bridging. Against
      excluded volume argumentation, salt addition was found to promote NCC nematic
      phase formation. Increased nematic ordering was observed in a transition regime
      of moderate salt addition before complete aggregation occurs. This regime is
      governed by an equilibrium of repulsive and attractive forces. Small angle
      neutron scattering suggests lateral orientation of NCC. Hence, NCC gelation and
      nematic ordering can be modulated via its zeta-potential by targeted salt
      addition.

PMID- 29028332
TI  - Coupling Light Emitting Diodes with Photocatalyst-Coated Optical Fibers Improves
      Quantum Yield of Pollutant Oxidation.
AB  - A photocatalyst-coated optical fiber was coupled with a 318 nm ultraviolet-A
      light emitting diode, which activated the photocatalysts by interfacial photon
      electron excitation while minimizing photonic energy losses due to conventional
      photocatalytic barriers. The light delivery mechanism was explored via modeling
      of evanescent wave energy produced upon total internal reflection and photon
      refraction into the TiO2 surface coating. This work explores aqueous phase LED
      irradiated optical fibers for treating organic pollutants and for the first time
      proposes a dual-mechanistic approach to light delivery and photocatalytic
      performance. Degradation of a probe organic pollutant was evaluated as a function
      of optical fiber coating thickness, fiber length, and photocatalyst attachment
      method and compared against the performance of an equivalent catalyst mass in a
      completely mixed slurry reactor. Measured and simulated photon fluence through
      the optical fibers decreased as a function of fiber length, coating thickness, or
      TiO2 mass externally coated on the fiber. Thinner TiO2 coatings achieved faster
      pollutant removal rates from solution, and dip coating performed better than sol
      gel attachment methods. TiO2 attached to optical fibers achieved a 5-fold higher
      quantum yield compared against an equivalent mass of TiO2 suspended in a slurry
      solution.

PMID- 29028333
TI  - Profiling and Quantification of Regioisomeric Caffeoyl Glucoses in Berry Fruits.
AB  - On the basis of a recently developed tandem mass spectrometry-based hierarchical
      scheme for the identification of regioisomeric caffeoyl glucoses, selected berry
      fruits were profiled for their caffeoyl glucose ester content. Fresh edible
      berries profiled, including strawberries, raspberries, blueberries, blackberries,
      red currant, black currant, lingonberries, gooseberries, and juices of
      elderberries, goji berries, chokeberries, cranberries, acai berries, sea
      buckthorn berries, Montmorency sour cherries, and pomegranates, were
      investigated. 1-Caffeoyl glucose was found to be the predominant isomer in the
      majority of samples, with further profiling revealing the presence of additional
      hydroxycinnamoyl glucose esters and O-glycosides with p-coumaroyl, feruloyl, and
      sinapoyl substituents. A quantitative liquid chromatography-mass spectrometry
      based method was developed and validated, and all caffeoyl glucose isomers were
      quantified for the first time in edible berries.

PMID- 29028334
TI  - Dynamic Control of Aptamer-Ligand Activity Using Strand Displacement Reactions.
AB  - Nucleic acid aptamers are an expandable toolkit of sensors and regulators. To
      employ aptamer regulators within nonequilibrium molecular networks, the aptamer
      ligand interactions should be tunable over time, so that functions within a given
      system can be activated or suppressed on demand. This is accomplished through
      complementary sequences to aptamers, which achieve programmable aptamer-ligand
      dissociation by displacing the aptamer from the ligand. We demonstrate the
      effectiveness of our simple approach on light-up aptamers as well as on aptamers
      inhibiting viral RNA polymerases, dynamically controlling the functionality of
      the aptamer-ligand complex. Mathematical models allow us to obtain estimates for
      the aptamer displacement kinetics. Our results suggest that aptamers, paired with
      their complement, could be used to build dynamic nucleic acid networks with
      direct control over a variety of aptamer-controllable enzymes and their
      downstream pathways.

PMID- 29028335
TI  - Metallo-supramolecular Complexes Enantioselectively Eradicate Cancer Stem Cells
      in Vivo.
AB  - Cancer stem cells (CSCs) are responsible for drug resistance, metastasis and
      recurrence of cancers. However, there is still no clinically approved drug that
      can effectively eradicate CSCs. Thus, it is crucial and important to develop
      specific CSC-targeting agents. Chiral molecular recognition of DNA plays an
      important role in rational drug design. Among them, polymorphic telomeric G
      quadruplex DNA has received much attention due to its significant roles in
      telomerase activity and chromosome stability. Herein, we find that one enantiomer
      of zinc-finger-like chiral metallohelices, [Ni2L3]4+-P, a telomeric G-quadruplex
      targeting ligand, can preferentially reduce cell growth in breast CSCs compared
      to the bulk cancer cells. In contrast, its enantiomer, [Ni2L3]4+-M, has little
      effect on both populations. Further studies indicate that [Ni2L3]4+-P can repress
      CSC properties and induce apoptosis in breast CSCs. This is different to the bulk
      cancer cells. The inhibition of breast CSC traits is involved in the nuclear
      translocation of hTERT. The apoptosis is associated with the induction of
      telomere uncapping, telomere DNA damage and the degradation of 3'-overhang.
      Moreover, [Ni2L3]4+-P, but not [Ni2L3]4+-M, has the ability to reduce
      tumorigenesis of breast CSCs in vivo. To our knowledge, this is the first report
      that chiral complexes show significant enantioselectivity on eradicating CSCs.

PMID- 29028336
TI  - Reaction of CO2 with UO3 Nanoclusters.
AB  - Adsorption of CO2 to uranium oxide, (UO3)n, clusters was modeled using density
      functional theory (DFT) and coupled cluster theory (CCSD(T)). Geometries and
      reaction energies were predicted for carbonate formation (chemisorption) and
      Lewis acid-base addition of CO2 (physisorption) to these (UO3)n clusters.
      Chemisorption of multiple CO2 moieties was also modeled for dimer and trimer
      clusters. Physisorption and chemisorption were both predicted to be
      thermodynamically allowed for (UO3)n clusters, with chemisorption being more
      thermodynamically favorable than physisorption. The most energetically favored
      (UO3)3(CO2)m clusters contain tridentate carbonates, which is consistent with
      solid-state and solution structures for uranyl carbonates. The calculations show
      that CO2 exposure is likely to convert (UO3)n to uranyl carbonates.

PMID- 29028337
TI  - Effect of Orbital Interactions between Vicinal Bonds and between Hydroxy Groups
      on the Conformational Stabilities of 1,2-Ethanediol and 2,3-Butanediols.
AB  - The geometries of the two hydroxy groups in 1,2-ethanediol or 2,3-butanediols are
      more stable in a gauche orientation than those in an anti orientation. This has
      been generally explained in terms of the gauche effect, which is stabilization
      due to antiperiplanar electron delocalization between an antibonding orbital of
      the C-O bond (sigmaCO*) and a bonding orbital of the C-H or C-C bond (sigmaCH or
      sigmaCC). However, a C-C single bond rotation simultaneously determines the
      geometries of the six vicinal bonds. Therefore, it is important to understand the
      effects on conformational stability of other interactions of the bond orbitals
      adjacent to the rotating C1-C2 bond. Bond model analysis revealed that
      antiperiplanar bond orbital interactions as a whole contribute to the higher
      stabilities of hydroxy/hydroxy gauche conformers, where the C-O/C-H or C-O/C-C
      combination including the sigmaCO*/sigmaCH or sigmaCO*/sigmaCC delocalization is
      not the dominant interaction stabilizing hydroxy/hydroxy gauche conformers.
      Rather, our results show that a large destabilization due to the antiperiplanar C
      O/C-O combination in hydroxy/hydroxy anti conformers relatively increases the
      stabilities of hydroxy/hydroxy gauche conformers. This destabilization results
      mainly from the repulsion between the antiperiplanar bonding orbitals
      (sigmaCO/sigmaCO), which have a larger overlap compared to the synclinal
      sigmaCO/sigmaCO combination. The sum of the interbond energies between the
      vicinal bond orbitals of these 1,2-alkanediols is more advantageous for stability
      in gauche conformers. In addition, interactions between the gauche-oriented
      hydroxy groups provide large stabilization energies and the corresponding
      interactions in anti conformers are negligible. The relative conformational
      stabilities of 1,2-ethanediol and erythro-2,3-butanediol can be explained by the
      interactions between the antiperiplanar bond orbitals, between the vicinal bond
      orbitals, or between the hydroxy groups in addition to the combination of
      interactions between the vicinal bond orbitals and between the hydroxy groups. In
      contrast, in threo-2,3-butanediol, differences in the relative stabilities of the
      three conformers can be understood by the combination of the interactions between
      the vicinal bond orbitals and between the hydroxy groups.

PMID- 29028339
TI  - Silver/Scandium-Cocatalyzed Bicyclization of beta-Alkynyl Ketones Leading to
      Benzo[c]xanthenes and Naphtho[1,2-b]benzofurans.
AB  - The combination of AgTFA and Sc(OTf)3 enables the bimetallic synergistic
      catalysis of beta-alkynyl ketones and para-quinone methides (p-QMs), allowing
      direct synthesis of 17 examples of benzo[c]xanthenes with generally good yields
      through a benzannulation/1,6-addition/cyclization sequence. Exchanging p-QMs for
      quinone imine ketal resulted in 10 examples of tetracyclic naphtho[1,2
      b]benzofurans via a similar benzannulation/1,4-addition/cyclization cascade.
      During these reaction processes, AgTFA and Sc(OTf)3 could be perfectly
      compatible, together with the realization of C(sp3)-H functionalization adjacent
      to carbonyl group on the beta-alkynyl ketone unit.

PMID- 29028338
TI  - Molecular Hybridization of Potent and Selective gamma-Hydroxybutyric Acid (GHB)
      Ligands: Design, Synthesis, Binding Studies, and Molecular Modeling of Novel 3
      Hydroxycyclopent-1-enecarboxylic Acid (HOCPCA) and trans-gamma-Hydroxycrotonic
      Acid (T-HCA) Analogs.
AB  - gamma-Hydroxybutyric acid (GHB) is a neuroactive substance with specific high
      affinity binding sites. To facilitate target identification and ligand
      optimization, we herein report a comprehensive structure-affinity relationship
      study for novel ligands targeting these binding sites. A molecular hybridization
      strategy was used based on the conformationally restricted 3-hydroxycyclopent-1
      enecarboxylic acid (HOCPCA) and the linear GHB analog trans-4-hydroxycrotonic
      acid (T-HCA). In general, all structural modifications performed on HOCPCA led to
      reduced affinity. In contrast, introduction of diaromatic substituents into the 4
      position of T-HCA led to high-affinity analogs (medium nanomolar Ki) for the GHB
      high-affinity binding sites as the most high-affinity analogs reported to date.
      The SAR data formed the basis for a three-dimensional pharmacophore model for GHB
      ligands, which identified molecular features important for high-affinity binding,
      with high predictive validity. These findings will be valuable in the further
      processes of both target characterization and ligand identification for the high
      affinity GHB binding sites.

PMID- 29028340
TI  - Probing the Binding Pathway of BRACO19 to a Parallel-Stranded Human Telomeric G
      Quadruplex Using Molecular Dynamics Binding Simulation with AMBER DNA OL15 and
      Ligand GAFF2 Force Fields.
AB  - Human telomeric DNA G-quadruplex has been identified as a good therapeutic target
      in cancer treatment. G-quadruplex-specific ligands that stabilize the G
      quadruplex have great potential to be developed as anticancer agents. Two crystal
      structures (an apo form of parallel stranded human telomeric G-quadruplex and its
      holo form in complex with BRACO19, a potent G-quadruplex ligand) have been
      solved, yet the binding mechanism and pathway remain elusive. In this study, we
      simulated the binding of a free BRACO19 molecule to the apo form of the G
      quadruplex using the latest AMBER DNA (OL15) and ligand (GAFF2) force fields.
      Three binding modes have been identified: top stacking, bottom intercalation, and
      groove binding. Bottom intercalation (51% of the population) resembles the bottom
      binding pose in the complex crystal structure very well. The groove binding mode
      is less stable than the bottom binding mode and is likely to be an intermediate
      state leading to the bottom binding mode. A flip-insertion mechanism was observed
      in the bottom intercalation mode, during which flipping of the bases outward
      makes space for ligand insertion, after which the bases flip back to increase the
      stability of the complex. In addition to reproducing the base-flipping behavior
      for some loop residues upon ligand binding, the direct alignment type of the ATAT
      tetrad was observed in our simulations for the first time. These successes
      provide initial support for using this combination of the OL15 and GAFF2 force
      fields to study quadruplex-ligand interactions.

PMID- 29028341
TI  - Highly Ordered Organic Ferroelectric DIPAB-Patterned Thin Films.
AB  - Ferroelectric molecular compounds present great advantages for application in
      electronics because they combine high polarization values, comparable to those of
      inorganic materials, with the flexibility and low-cost properties of organic
      ones. However, some limitations to their applicability are related to the high
      crystallinity required to deploy ferroelectricity. In this article, highly
      ordered ferroelectric patterned thin films of diisopropylammonium bromide have
      been successfully fabricated by a lithographically controlled wetting technique.
      Confinement favors the self-organization of ferroelectric crystals, avoiding the
      formation of polymorphs and promoting the long-range orientation of
      crystallographic axes. Patterned structures present high stability, and the
      polarization can be switched to be arranged in stable domain pattern for
      application in devices.

PMID- 29028342
TI  - Radical-Pair-Based Magnetoreception Amplified by Radical Scavenging: Resilience
      to Spin Relaxation.
AB  - Birds and several other species are equipped with the remarkable ability to sense
      the geomagnetic field for the purpose of navigation and orientation. The primary
      detection mechanism of this compass sense is uncertain but appears to originate
      from a truly quantum process involving spin-correlated radical pairs. In order to
      elicit sensitivity to weak magnetic fields, such as the Earth's magnetic field,
      the underlying spin dynamics must be protected from fast decoherence. In this
      work, we elucidate the effects of spin relaxation on a recently suggested
      reaction scheme involving three radicals, instead of a radical pair, doublet
      quartet interconversion under magnetic interactions, and a spin-selective
      scavenging reaction. We show that, besides giving rise to a vastly enhanced
      reaction anisotropy, this extended reaction scheme is more resilient to spin
      relaxation than the conventional radical pair mechanism. Surprisingly, the
      anisotropic magnetic field effect can be enhanced by fast spin relaxation in one
      of the radicals of the primary pair. We discuss this finding in the context of
      magnetoreception. Radical scavenging can protect the spin system against fast
      spin relaxation in one of the radicals, thereby providing a credible model to the
      involvement of fast relaxing radical pairs, such as FADH*/O2*-, in radical-pair
      based magnetoreception. This finding will help explain behavioral observations
      that seem incompatible with the previously proposed flavin
      semiquinone/tryptophanyl radical pair.

PMID- 29028343
TI  - Synthesis of Substituted Quinazolin-4(3H)-imines From Aryldiazonium Salts,
      Nitriles and 2-Cyanoanilines via A Metal-Free Tandem Approach.
AB  - A transition metal-free synthesis of multisubstituted quinazolin-4(3H)-imines has
      been realized by the direct reaction of aryldiazonium salts, nitriles, and 2
      cyanoanilines in a one-pot fashion. This strategy utilizes the in situ formation
      of reactive N-arylnitrilium intermediate, which undergoes further tandem
      cyclization with consecutive formation of N-C bonds. Broad functional group
      compatibility, mild conditions, shorter time, and operational simplicity are the
      notable features of this report.

PMID- 29028344
TI  - Gelling Lamellar Phases of the Binary System Water-Didodecyldimethylammonium
      Bromide with an Organogelator.
AB  - Does the presence of a gel network influence the properties of a lyotropic liquid
      crystal? Does the replacement of oil by a lyotropic liquid crystal influence the
      properties of an organogel? To answer these questions we study gelled lyotropic
      liquid crystals (LLC). In the present study we show that it is possible to gel
      the lamellar phase of the binary system water-didodecyl dimethylammonium bromide
      (2C12DAB) with the organogelator 12-hydroxyoctadecanoic acid (12-HOA). We compare
      various properties of the gelled LLC phases with the "parent systems", i.e., with
      the binary organogel consisting of n-decane-12-HOA and with the nongelled LC
      phases, respectively. Optical and electron microscopy, differential scanning
      calorimetry (DSC), rheometry, as well as small and wide-angle X-ray scattering
      (SWAXS) proved the coexistence of an Lalpha phase and a 12-HOA gel network in the
      gelled Lalpha phase. However, a small influence of the Lalpha phase on the gel
      properties was seen, namely slightly lower sol-gel transition temperatures and
      viscoelastic moduli of the gelled Lalpha phase compared to the binary gel. On the
      other hand, the presence of the gel also has an influence on the Lalpha phase:
      the interlayer spacing of the surfactant bilayers in the gelled Lalpha phases is
      slightly larger compared to the nongelled Lalpha phases, which is due to mixing
      part of the 12-HOA molecules in the Lalpha bilayers. Despite this mutual
      influence the structures of both the Lalpha phase and the gel network are hardly
      disturbed in the gelled Lalpha phase, i.e., that the self-assembly of the
      surfactant and of the gelator molecules clearly occur in an orthogonal way.

PMID- 29028345
TI  - Iron-Catalyzed Carbene Insertion Reactions of alpha-Diazoesters into Si-H Bonds.
AB  - An efficient iron-catalyzed carbene insertion reaction of alpha-diazo carbonyl
      compounds into the Si-H bond was developed. A wide range of alpha-silylesters was
      obtained in high yields (up to 99%) from alpha-diazoesters using a simple
      iron(II) salt as catalyst.

PMID- 29028346
TI  - Influence of Hofmeister I- on Tuning Optoelectronic Properties of Ampholytic
      Polythiophene by Varying pH and Conjugating with RNA.
AB  - A significant tuning of optoelectronic properties of polythiophene (PT) chains
      due to Hofmeister iodide (I-) ion is demonstrated in ampholytic polythiophene
      [polythiophene-g-poly{(N,N,N-trimethylamino iodide)ethyl methacrylate-co
      methacrylic acid}, APT] at different pHs. In acidic medium, the absorption and
      emission signals of PT chromophore exhibit appreciable blue shift in the presence
      of I- as counteranion only. The cooperative effect of undissociated -COOH and
      quaternary ammonium groups immobilize I- near the apolar PT chain causing
      threading of grafted chains and hence twisting of the backbone attributing to the
      blue shift. As medium pH is increased, dethreading of the PT backbone occurs due
      to ionization of -COOH group, releasing quencher iodide ions from the vicinity of
      the PT chains resulting in a red shift in absorption and a sharp hike in
      fluorescence intensity (390 times) for an increase of excitons lifetime. With an
      increase of pH, morphology changes from a multivesicular aggregate with vacuoles
      to smaller size vesicles and finally to nanofibrillar network structure.
      Dethreading is also found when APT interacts with RNA showing a significant hike
      of fluorescence (22 times) for displacing iodide ions forming a nanofibrillar
      network morphology. Threading and dethreading also affect the resistance,
      capacitance, and Warburg impedance values of APT. Molecular dynamics simulation
      of a model APT chain in a water box supports the threading at lower pH where the
      iodide ions pose nearer to the PT chain than that at higher pH causing
      dethreading. So the influence of Hofmeister I- ion is established for tuning the
      optoelectronic properties of a novel PT based polyampholyte by changing pH or by
      conjugating with RNA.

PMID- 29028347
TI  - Switchable Plasmonic Metasurfaces with High Chromaticity Containing Only Abundant
      Metals.
AB  - Plasmonic color generation offers several advantages but is also limited by the
      cost and availability of noble metals like gold. In this work, we present color
      tunable metasurfaces with high chromaticity and reflectivity consisting of an
      aluminum mirror, a dielectric spacer, and a plasmonic nanohole array in copper.
      Copper is shown to be an excellent alternative to gold when properly protected
      from oxidation and makes it possible to generate a wide RGB gamut covering 27% of
      the standard RGB. By patterning the metasurfaces into microscale pixel triplets,
      color photos can be well reproduced with high resolution over wafer-sized areas.
      Further, we demonstrate active modulation of the reflected intensity using an
      electrochromic conductive polymer deposited on top of the nanostructures by
      screen printing. This technology opens up for ultrathin and flexible reflective
      displays in full color, that is, plasmonic electronic paper, compatible with
      large-scale sustainable production.

PMID- 29028348
TI  - Directed Organization of Platinum Nanocrystals through Organic Supramolecular
      Nanoporous Templates.
AB  - We propose a novel approach to trap 2 nm Pt nanocrystals using nanoporous two
      dimensional supramolecular networks for cavity-confined host-guest recognition
      process. This will be achieved by taking advantage of two features of
      supramolecular self-assembly at surfaces: First, its capability to allow the
      formation of complex 2D architectures, more particularly, nanoporous networks,
      through noncovalent interactions between organic molecular building-blocks;
      second, the ability of the nanopores to selectively host and immobilize a large
      variety of guest species. In this paper, for the first time, we will use
      isotropic honeycomb networks and anisotropic linear porous supramolecular
      networks to host 2 nm Pt nanocrystals.

PMID- 29028349
TI  - Proteomic Profiling of beta-hCG-Induced Spheres in BRCA1 Defective Triple
      Negative Breast Cancer Cells.
AB  - Previously, we identified that beta-hCG is expressed by BRCA1 mutated but not
      wild type breast cancers in vitro/in vivo and exhibited a novel event in beta-hCG
      overexpressing BRCA1 mutated HCC1937 cells where the cells were able to form
      spheres (HCC1937 beta spheres) in adherent cell culture plates even in the
      absence of any growth factors. These spheres express stem cell and EMT markers.
      In the present study, we carried out the total proteomic profiling of these
      HCC1937 beta spheres obtained from BRCA1 defective beta-hCG expressing stable
      breast cancer cells to analyze the cell signaling pathways that are active in
      these cells. Functional annotation revealed proteins (164 cellular and 97
      secretory) predominantly involved in oxygen binding, nucleosome assembly,
      cytoskeleton organization, protein folding, etc. Many of the proteins identified
      from HCC1937 beta spheres in this study are also up regulated in breast cancers,
      which are directly linked with poor prognosis in human cancer samples as analyzed
      using TCGA data set. Survival analysis shows that beta-hCG expressing cancer
      patients are linked with poor survival rate. Interestingly, hemoglobins were
      identified at both cellular and secretory level in HCC1937 beta spheres and
      experiments after treating with ROS inducers revealed that beta-hCG induces
      hemoglobin and protects the cancer cells during oxidative stress. Our proteomic
      data strongly propose beta-hCG as an oncogenic molecule associated with BRCA1
      mutation, and hence, targeting beta-hCG could be a strategy to treat BRCA1
      defective breast cancers.

PMID- 29028350
TI  - Asymmetric Synthesis of (-)-6'-beta-Fluoro-aristeromycin via Stereoselective
      Electrophilic Fluorination.
AB  - (-)-6'-beta-Fluoro-aristeromycin (2), a potent inhibitor of S
      adenosylhomocysteine (AdoHcy) hydrolase, has been synthesized via stereoselective
      electrophilic fluorination followed by a purine base build-up approach.
      Interestingly, purine base condensation using a cyclic sulfate resulted in a
      synthesis of (+)-5'-beta-fluoro-isoaristeromycin (2a). Computational analysis
      indicates that the fluorine atom controlled the regioselectivity of the purine
      base substitution.

PMID- 29028352
TI  - Effect of Dimensionality and Doping in Quasi-"One-Dimensional (1-D)" Nitrogen
      Doped Graphene Nanoribbons on the Oxygen Reduction Reaction.
AB  - Designing an efficient metal-free electrocatalyst for the oxygen reduction
      reaction (ORR) is a challenging research theme having enormous practical
      importance in several renewable energy technologies like fuel cell and metal-air
      batteries. Here we discuss a cost-effective and commercially viable strategy to
      develop high-performance nitrogen-doped graphene nanoribbon (N-GNR), which is a
      quasi-"one-dimensional" analogue of graphene. We have selected the N-GNR system
      to identify the doping-induced variation in the distribution of active catalytic
      sites experimentally in graphene-based electrocatalysts. N-GNR exhibits a
      comparable exchange current density (1.65 * 10-9 vs 2.25 * 10-9 A cm-2),
      thermodynamic potential (0.80 vs 0.83 V), and smaller Tafel slope (55 vs 60 mV
      dec-1) with respect to the benchmarking platinum/carbon (Pt/C), and also, more
      precisely, it goes through a four-electron pathway with low hydrogen peroxide
      yield. Although the exact mechanism is still not clear, the theme of the work is
      based on the identification of the possible active sites with the help of
      experimental evidence like X-ray photoelectron spectroscopy. These results
      support the assumption that an edge N (pyridinic N)-bonded adjacent C lowers the
      activation energy barriers of O2 adsorption, predominantly to kinetically
      facilitate the ORR activity. We hope these results will be helpful in developing
      more efficient ORR catalysts.

PMID- 29028351
TI  - A Hexamer of a Peptide Derived from Abeta16-36.
AB  - The absence of high-resolution structures of amyloid oligomers constitutes a
      major gap in our understanding of amyloid diseases. A growing body of evidence
      indicates that oligomers of the beta-amyloid peptide Abeta are especially
      important in the progression of Alzheimer's disease. In many Abeta oligomers, the
      Abeta monomer components are thought to adopt a beta-hairpin conformation. This
      paper describes the design and study of a macrocyclic beta-hairpin peptide
      derived from Abeta16-36. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and size exclusion chromatography studies show that the Abeta16
      36 beta-hairpin peptide assembles in solution to form hexamers, trimers, and
      dimers. X-ray crystallography reveals that the peptide assembles to form a
      hexamer in the crystal state and that the hexamer is composed of dimers and
      trimers. Lactate dehydrogenase release assays show that the oligomers formed by
      the Abeta16-36 beta-hairpin peptide are toxic toward neuronally derived SH-SY5Y
      cells. Replica-exchange molecular dynamics demonstrates that the hexamer can
      accommodate full-length Abeta. These findings expand our understanding of the
      structure, solution-phase behavior, and biological activity of Abeta oligomers
      and may offer insights into the molecular basis of Alzheimer's disease.

PMID- 29028354
TI  - Nanosheet Array-Like Palladium-Catalysts Pdx/rGO@CoAl-LDH via Lattice Atomic
      Confined in Situ Reduction for Highly Efficient Heck Coupling Reaction.
AB  - A series of novel nanosheet array-like catalysts Pdx/rGO@CoAl-LDH (x = 0.0098
      1.9, refers to Pd loading in wt % on ICP, rGO: reduced graphene oxide, LDH:
      layered double hydroxide) were first prepared via a simple and green lattice
      atomic-confined in situ reduction of oxidative Pd precursors by the evenly atomic
      dispersed reductive Co2+ sites on LDH layers of a nanohybrid rGO@CoAl-LDH with
      hexagonal LDH nanoplates (~73 * 7 nm) interdigitated vertical to the surfaces of
      rGO layer in both sides, fabricated through a simple citric acid-assisted aqueous
      phase coprecipitation method. The as-obtained Pd catalysts possess clean Pd
      nanoclusters (NCs) with tunable sizes in 1.3-1.8 nm on varied Pd loadings. All
      the Pdx/rGO@CoAl-LDH catalysts show excellent activities for the Heck reaction,
      and the Pd0.0098/rGO@CoAl-LDH with the ultrafine Pd NCs of 1.3 +/- 0.2 nm yields
      a maximum turnover frequency of 160 000 h-1 over a heterogeneous catalyst so far.
      The excellent activities can be attributed to the ultrasmall Pd NCs with high
      dispersion and clean Pd surfaces, increased electron transfer capacity and
      surface area, and remarkable Pd-CoAl-LDH-rGO three-phase synergistic effect of
      the present unique nanosheet array-like Pd NCs catalysts. Moreover, the catalyst
      Pd0.33/rGO@CoAl-LDH shows a broad range of substrate applicability and can be
      reused more than five runs without obvious loss of activity, giving the present
      catalysts long-term stability. These findings make the rGO@CoAl-LDH hybrid
      prepared by a facile and scalable synthesis route a universal green platform to
      support other noble or nonprecious metal NCs via lattice atomic-confined in situ
      reduction strategy to construct more desired heterogeneous catalysts.

PMID- 29028355
TI  - Ion Transport and Competition Effects on NaTi2(PO4)3 and Na4Mn9O18 Selective
      Insertion Electrode Performance.
AB  - We evaluate the efficiency and capacity of electrochemically reversible insertion
      electrodes for use in targeted ion removal applications in aqueous solutions. The
      relative attributes of insertion material chemistry are evaluated by comparing
      the performance of two different sodium insertion materials, NaTi2(PO4)3 and
      Na4Mn9O18, in different electrolyte environments. We performed experiments over a
      range of solution compositions containing both sodium and other non-inserting
      ions, and we then developed mechanistic insight into the effects of solution
      concentration and composition on overpotential losses and round trip Coulombic
      efficiency. In dilute aqueous streams, performance was limited by the rate of ion
      transport from the bulk electrolyte region to the electrode interface. This leads
      to slow rates of ion removal, large overpotentials for ion insertion, parasitic
      charge loss due to water electrolysis, and lower round trip Coulombic
      efficiencies. This effect is particularly large for insertion electrodes with
      redox potentials exceeding the water stability window. In solutions with high
      background concentrations of non-inserting ions, the accumulation of non
      inserting ions at the electrode interface limits inserting ion flux and leads to
      low ion removal capacity and round trip Coulombic efficiency.

PMID- 29028353
TI  - Activated Microglia Targeting Dendrimer-Minocycline Conjugate as Therapeutics for
      Neuroinflammation.
AB  - Brain-related disorders have outmatched cancer and cardiovascular diseases
      worldwide as the leading cause of morbidity and mortality. The lack of effective
      therapies and the relatively dry central nervous system (CNS) drug pipeline pose
      formidable challenge. Superior, targeted delivery of current clinically approved
      drugs may offer significant potential. Minocycline has shown promise for the
      treatment of neurological diseases owing to its ability to penetrate the blood
      brain barrier (BBB) and potency. Despite its potential in the clinic and in
      preclinical models, the high doses needed to affect a positive therapeutic
      response have led to side effects. Targeted delivery of minocycline to the
      injured site and injured cells in the brain can be highly beneficial.
      Systemically administered hydroxyl poly(amidoamine) (PAMAM) generation-6 (G6)
      dendrimers have a longer blood circulation time and have been shown to cross the
      impaired BBB. We have successfully prepared and characterized the in vitro
      efficacy and in vivo targeting ability of hydroxyl-G6 PAMAM dendrimer-9-amino
      minocycline conjugate (D-mino). Minocycline is a challenging drug to carry out
      chemical transformations due to its inherent instability. We used a combination
      of a highly efficient and mild copper catalyzed azide-alkyne click reaction
      (CuAAC) along with microwave energy to conjugate 9-amino-minocycline (mino) to
      the dendrimer surface via enzyme responsive linkages. D-mino was further
      evaluated for anti-inflammatory and antioxidant activity in lipopolysaccharides
      activated murine microglial cells. D-mino conjugates enhanced the intracellular
      availability of the drug due to their rapid uptake, suppressed inflammatory
      cytokine tumor necrosis factor alpha (TNF-alpha) production, and reduced
      oxidative stress by suppressing nitric oxide production, all significantly better
      than the free drug. Fluorescently labeled dendrimer conjugate (Cy5-D-mino) was
      systematically administered (intravenous, 55 mg/kg) on postnatal day 1 to rabbit
      kits with a clinically relevant phenotype of cerebral palsy. The in vivo imaging
      study indicates that Cy5-D-mino crossed the impaired blood-brain barrier and co
      localized with activated microglia at the periventricular white matter areas,
      including the corpus callosum and the angle of the lateral ventricle, with
      significant implications for positive therapeutic outcomes. The enhanced efficacy
      of D-mino, when combined with the inherent neuroinflammation-targeting capability
      of the PAMAM dendrimers, may provide new opportunities for targeted drug delivery
      to treat neurological disorders.

PMID- 29028356
TI  - Aggregation of a Cationic Gemini Surfactant with a Chelating Molecule and Effects
      from Calcium Ions.
AB  - The aggregation behavior of cationic ammonium gemini surfactant hexamethylene-1,6
      bis(dodecyldimethylammonium bromide) (12-6-12) with chelating molecule
      ethylenediaminetetraacetic acid (EDTA) and the effects of calcium bromide (CaBr2)
      on the structure and morphology of the aggregates in the mixture have been
      investigated by surface tension, isothermal titration microcalorimetry,
      electrical conductivity, zeta potential, dynamic light scattering, cryogenic
      transmission electron microscopy, freeze-fracture transmission electron
      microscopy, and 1H NMR techniques. It was found that the electrostatic attraction
      between the carboxyl groups of EDTA and the headgroups of 12-6-12 leads to the
      formation of oligomeric-like surfactant EDTA(12-6-12)2 at an EDTA/12-6-12 molar
      ratio of 0.50. The critical aggregation concentration of the EDTA(12-6-12)2
      complexes is much lower than that of 12-6-12, and the complexes form loose, large
      network-like premicellar aggregates and then transfer into small micelles with an
      increase in concentration. Moreover, the addition of CaBr2 induces the transition
      from the loose aggregates and micelles to vesicles owing to the coordination
      interaction between the calcium ion and EDTA and the electrostatic interaction
      between EDTA and 12-6-12. The work reveals that as a bridging molecule between
      the calcium ion and the gemini surfactant, the chelating molecule greatly
      promotes the assembly of the gemini surfactant and strengthens the molecular
      packing in the presence of calcium ions.

PMID- 29028358
TI  - Posterior Tibial Translation Measurements on Magnetic Resonance Imaging Improve
      Diagnostic Sensitivity for Chronic Posterior Cruciate Ligament Injuries and Graft
      Tears.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) of the knee is a highly sensitive
      and specific method for diagnosing acute posterior cruciate ligament (PCL) tears,
      with a reported accuracy of 96% to 100%. In chronic and revision settings, these
      injuries may be missed on MRI because of the apparent continuity of nonfunctional
      PCL fibers. Posterior tibial translation (PTT) of the medial compartment has been
      identified as a potential secondary finding of PCL tear on routine MRI.
      Purpose/Hypothesis: The purpose of this study was to evaluate the sensitivity of
      PTT on MRI associated with PCL injuries and compare it with the sensitivity of a
      radiologist's MRI interpretation with preoperative posterior knee stress
      radiographs as the gold standard. Our hypothesis was that the MRI measurement of
      PTT of the medial compartment would improve diagnostic sensitivity as compared
      with the diagnosis made by the interpreting radiologist's evaluation of the
      continuity of the PCL fibers for chronic and postrecostruction graft injuries.
      STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Cases of
      patients who underwent a primary or revision PCL reconstruction, without anterior
      cruciate ligament injury, by a single surgeon between 2010 and 2016 were
      retrospectively analyzed. Measurements of medial and lateral compartment PTT were
      performed with the MRI of PCL-injured cases and controls without clinical or MRI
      evidence of ligamentous injury. The sensitivity of this technique was compared
      with the preoperative MRI diagnosis determined by review of the musculoskeletal
      radiologist's report and confirmed by the gold standard of posterior knee stress
      radiographs. The sensitivity of medial compartment PTT was determined by receiver
      operator characteristic (ROC) analysis and compared with the MRI sensitivity for
      chronic PCL and PCL graft tears. RESULTS: One hundred patients (80 males and 20
      females) with a mean age of 31.1 years (range, 15-66 years) met the inclusion
      criteria: 57 acute primary tears, 32 chronic primary, and 11 PCL graft tears. MRI
      sensitivity was 100% for acute primary PCL tears, 62.5% for chronic primary PCL
      tears, and 18.1% for PCL graft tears. There were significant differences in
      medial compartment PTT on MRI for acute versus chronic injuries ( P = .025) and
      acute versus graft injuries ( P = .007). ROC curve analysis indicated that the
      most accurate cutoff point for the detection of chronic PCL tears was 2.0 mm of
      medial compartment PTT on MRI, with a sensitivity and specificity of 0.80 and
      0.89, respectively. For PCL graft injuries, the ROC curve indicated that the most
      accurate medial compartment PTT cutoff for the detection of PCL graft failure was
      3.6 mm (sensitivity, 0.92; specificity, 0.72). CONCLUSION: MRI evaluation of the
      PCL fibers had poor sensitivity for chronic PCL tears and PCL reconstruction
      graft tears. The sensitivity for diagnosing chronic PCL tears and PCL
      reconstruction graft failures was improved by measuring posteromedial tibial
      translation.

PMID- 29028357
TI  - Folate-PEG-NOTA-Al18F: A New Folate Based Radiotracer for PET Imaging of Folate
      Receptor-Positive Tumors.
AB  - The folate receptor (FR) has been established as a promising target for imaging
      and therapy of cancer (FR-alpha), inflammation, and autoimmune diseases (FR
      beta). Several folate based PET radiotracers have been reported in the
      literature, but an 18F-labeled folate-PET imaging agent with optimal properties
      for clinical translation is still lacking. In the present study, we report the
      design and preclinical evaluation of folate-PEG12-NOTA-Al18F (1), a new folate
      PET agent with improved potential for clinical applications. Radiochemical
      synthesis of 1 was achieved via a one-pot labeling process by heating folate
      PEG12-NOTA in the presence of in situ prepared Al18F for 15 min at 105  degrees
      C, followed by HPLC purification. Specific binding of 1 to FR was evaluated on
      homogenates of KB (FR-positive) and A549 (FR-deficient) tumor xenografts in the
      presence and absence of excess folate. In vivo tumor imaging with folate-PEG12
      NOTA-Al18F was compared to imaging with 99mTc-EC20 using nu/nu mice bearing
      either KB or A549 tumor xenografts. Specific accumulation of 1 in tumor and other
      tissues was assessed by high-resolution micro-PET and ex vivo biodistribution in
      the presence and absence of excess folate. Radiosynthesis of 1 was accomplished
      within ~35 min, affording pure radiotracer 1 in 8.4 +/- 1.3% (decay corrected)
      radiochemical yield with ~100% radiochemical purity after HPLC purification and a
      specific activity of 35.8 +/- 15.3 GBq/mmol. Further in vitro and in vivo
      examination of 1 demonstrated highly specific FR-mediated uptake in FR+ tumor,
      with Kd of ~0.4 nM (KB), and reduced accumulation in liver. Given its facile
      preparation and improved properties, the new radiotracer, folate-PEG12-NOTA-Al18F
      (1), constitutes a promising tool for identification and classification of
      patients with FR overexpressing cancers.

PMID- 29028360
TI  - A Predictive Model for the Growth of Listeria monocytogenes in Commercial Blue
      Crab (Callinectes sapidus).
AB  - During the processing and handling of commercial blue crab (Callinectes sapidus),
      Listeria monocytogenes can potentially contaminate cooked meat and grow to
      hazardous levels. To manage this risk, predictive models are useful tools for
      designing and implementing preventive controls; however, no model specific for
      blue crab meat has been published or evaluated. In this study, a cocktail of L.
      monocytogenes strains was added to pasteurized blue crab meat, which was
      incubated at storage temperatures from 0 to 35 degrees C. At selected time
      intervals, L. monocytogenes was enumerated by direct plating onto modified Oxford
      agar. A primary model was fitted to kinetic data to estimate the lag-phase
      duration (LPD) and growth rate (GR). Listeria monocytogenes replicated from 0 to
      35 degrees C, with GR ranging from 0.004 to 0.518 log CFU/h. Overall, the LPD
      decreased with increasing temperature, displaying a maximum value of 187 h at 0
      degrees C; however, this trend was not consistent. The LPD was not detected at 10
      degrees C, and it occurred inconsistently from trial to trial. A secondary GR
      model (R2 = 0.9892) for pasteurized crab meat was compared with the L.
      monocytogenes GR in fresh crab meat, demonstrating bias and accuracy factors of
      0.98 and 1.36, respectively. The model estimates varied from other published data
      and models, especially at temperatures >=5 degrees C, supporting the need for a
      specific predictive tool for temperature deviations.

PMID- 29028359
TI  - Complex interaction between circadian rhythm and diet on bile acid homeostasis in
      male rats.
AB  - Desynchronization between the master clock in the brain, which is entrained by
      (day) light, and peripheral organ clocks, which are mainly entrained by food
      intake, may have negative effects on energy metabolism. Bile acid metabolism
      follows a clear day/night rhythm. We investigated whether in rats on a normal
      chow diet the daily rhythm of plasma bile acids and hepatic expression of bile
      acid metabolic genes is controlled by the light/dark cycle or the feeding/fasting
      rhythm. In addition, we investigated the effects of high caloric diets and time
      restricted feeding on daily rhythms of plasma bile acids and hepatic genes
      involved in bile acid synthesis. In experiment 1 male Wistar rats were fed
      according to three different feeding paradigms: food was available ad libitum for
      24 h (ad lib) or time-restricted for 10 h during the dark period (dark fed) or 10
      h during the light period (light fed). To allow further metabolic phenotyping, we
      manipulated dietary macronutrient intake by providing rats with a chow diet, a
      free choice high-fat-high-sugar diet or a free choice high-fat (HF) diet. In
      experiment 2 rats were fed a normal chow diet, but food was either available in a
      6-meals-a-day (6M) scheme or ad lib. During both experiments, we measured plasma
      bile acid levels and hepatic mRNA expression of genes involved in bile acid
      metabolism at eight different time points during 24 h. Time-restricted feeding
      enhanced the daily rhythm in plasma bile acid concentrations. Plasma bile acid
      concentrations are highest during fasting and dropped during the period of food
      intake with all diets. An HF-containing diet changed bile acid pool composition,
      but not the daily rhythmicity of plasma bile acid levels. Daily rhythms of
      hepatic Cyp7a1 and Cyp8b1 mRNA expression followed the hepatic molecular clock,
      whereas for Shp expression food intake was leading. Combining an HF diet with
      feeding in the light/inactive period annulled CYp7a1 and Cyp8b1 gene expression
      rhythms, whilst keeping that of Shp intact. In conclusion, plasma bile acids and
      key genes in bile acid biosynthesis are entrained by food intake as well as the
      hepatic molecular clock. Eating during the inactivity period induced changes in
      the plasma bile acid pool composition similar to those induced by HF feeding.

PMID- 29028361
TI  - New Findings on Biological Actions and Clinical Applications of Royal Jelly: A
      Review.
AB  - Royal jelly (RJ) is a natural bee product with great potential for use in
      medicine. The chemical composition of RJ indicates the presence of various
      bioactive substances including 10-hydroxydecanoic acid and 24
      methylenecholesterol. In addition, a number of biological and pharmacological
      activities of RJ have been documented. The aim of this study was to review the
      biological and medical effects of RJ. The search was conducted in articles from
      electronic and scientific literature databases such as Pub Med, Science Direct,
      Scopus, Medline, and ISI Web of Science published from 1990 to 2017 using
      keywords of pharmacological, biological, and clinical effects and royal jelly.
      Data were chosen after the primary survey of all abstracts and selected full
      articles. Comparison among related data was done by the authors. Literature has
      shown that RJ possesses many beneficial effects on biological systems. For
      example, the therapeutic uses of RJ have been reported in several diseases such
      as hypercholesterolemia, diabetes, hypertension, and cancers. It was also found
      to possess neurotrophic, hypotensive, immunomodulatory, antimicrobial,
      antioxidant, antidiabetic, antihypercholesterolemic, antitumor, and anti
      inflammatory effects. Owing to the broad spectrum of biological effects and
      valuable clinical trials, evaluating the beneficial pharmaceutical effects of RJ
      in animal and human models seems to be important.

PMID- 29028362
TI  - The Current Socio-Political Climate and Psychological Distress Among Transgender
      People.

PMID- 29028363
TI  - SUMMARY: GLIDING THROUGH THE GOLDEN YEARS GRACEFULLY.

PMID- 29028364
TI  - The Effectiveness of Empowerment Program on Increasing Self-Esteem, Learned
      Resourcefulness, and Coping Ways in Women Exposed to Domestic Violence.
AB  - This study was conducted to assess the effectiveness of empowerment program on
      increasing self-esteem, learned resourcefulness, and coping ways in women exposed
      to domestic violence. This experimental study was conducted between October 2012
      and June 2014 in the obstetrics and gynaecology departments of the Giresun
      Maternity Hospital, and at the Family Counseling Center (FCC) in Turkey. Sixty
      women who agreed to participate in the study were randomly assigned into two
      groups. Data were collected by the Coopersmith Self-Esteem Inventory (SEI), The
      Rosenbaum's Learned Resourcefulness Scale (RLRS), and the Ways of Coping
      Inventory (WCI). The assessment of the women before and after the empowerment
      program showed that women in the intervention group showed significant
      improvements in the SEI, RLRS, and WCI scores compared with controls. These
      results suggest that the empowerment program is an effective practice for
      increasing the levels of self-esteem, learned resourcefulness, and coping ways of
      women exposed to domestic violence.

PMID- 29028365
TI  - Exploring Self-Care and Preferred Supports for Adult Parents in Recovery from
      Substance Use Disorders: Qualitative Findings from a Feasibility Study.
AB  - Very little is known about the self-care behaviors (SCB) that adult parents
      employ and the preferred supports they utilize to maintain their recovery from
      substance use disorders (SUD) while also parenting their children. This study
      used a qualitative descriptive approach to explore perceptions of self-care and
      parenting to inform future self-care interventions for parents in early recovery.
      Nineteen mothers and fathers of at least one child between the ages of 6-18 were
      interviewed by telephone about parental self-care practices while in recovery
      from SUD, recovery management, and preferred supports in the community.
      Participants described the experience of parenting as challenging, with
      variations in the level of support and resources. Self-care included meaningful
      connection with recovery support and children, taking care of physical health,
      maintaining spirituality, healthy eating, exercise, journaling, continuing
      education, staying busy, sponsorship, establishing boundaries, self-monitoring,
      abstinence, and dealing with destructive emotions. Participants reported SCB as
      being a critical component of their ongoing recovery and their parenting
      practices, though differences in SCB by gender and for minorities require further
      exploration. Parental gains were perceived as benefits of SCB that minimized the
      negative impact of prior parental drug use on their children.

PMID- 29028366
TI  - Synthesis, modeling and biological evaluation of hybrids from
      pyrazolo[1,5c]pyrimidine as antileishmanial agents.
AB  - AIM: A new series of pyrazolo[1,5-c]pyrimidines were synthesized by different
      hybridization strategies. METHODOLOGY: All structures were confirmed by IR, 1H,
      13C, 1H-13C heteronuclear multiple-quantum correlation (HMQC) spectra and
      microanalysis. They were evaluated for their in vitro antileishmanial activity
      against miltefosine and amphotericin B deoxycholate as reference drugs. RESULTS:
      The most active compounds 2a and 9a demonstrated superior potencies to
      miltefosine by ten- and six-fold, respectively, for the promastigote form, and by
      5.5-fold for the amastigote form. Their binding scenario to Leishmania major
      pteridine reductase was rationalized by docking experiments. In addition, all
      compounds were safe for the experimental animals orally up to 150 mg/kg and
      parenterally up to 75 mg/kg. CONCLUSION: This study provides novel chemotype
      class for antileishmanial activity. [Formula: see text].

PMID- 29028367
TI  - Philip Hillkowitz The "Granddaddy of Medical Technologists" and Cofounder of the
      American Society for Clinical Pathologists and the Jewish Consumptives' Relief
      Society.
AB  - CONTEXT: - In the early 20th century, the future of hospital-based clinical
      pathology practice was uncertain and this situation led to the formation of the
      American Society for Clinical Pathologists in 1922. Philip Hillkowitz, MD, and
      Ward Burdick, MD, were its cofounders. No biography of Hillkowitz exists.
      OBJECTIVE: - To explore the life, beliefs, and accomplishments of Philip
      Hillkowitz. DESIGN: - Available primary and secondary historical sources were
      reviewed. RESULTS: - Hillkowitz, the son of a Russian rabbi, immigrated to
      America as an 11-year-old child in 1885. He later attended medical school in
      Cincinnati, Ohio, and then moved to Colorado, where he began his clinical
      practice, which transitioned into a clinical pathology practice. In Denver, he
      met Charles Spivak, MD, another Jewish immigrant and together they established
      the Jewish Consumptives' Relief Society, an ethnically sensitive tuberculosis
      sanatorium that flourished in the first half of the 20th century because of its
      national fundraising network. In 1921, Hillkowitz and Burdick, also a Denver
      based pathologist, successively organized the pathologists in Denver, followed by
      the state of Colorado. Early the next year, they formed the American Society for
      Clinical Pathologists (ASCP). Working with the American College of Surgeons, the
      ASCP put hospital-based practice of clinical pathology on solid footing in the
      1920s. Hillkowitz then established and oversaw the ASCP Board of Registry of
      Medical Technologists. CONCLUSIONS: - Philip Hillkowitz changed the directions of
      clinical pathology and tuberculosis treatment in 20th century America, while
      simultaneously serving as a successful ethnic power broker within both the
      American Jewish and Eastern European immigrant communities.

PMID- 29028368
TI  - A Window Into Clinical Next-Generation Sequencing-Based Oncology Testing
      Practices.
AB  - CONTEXT: - Detection of acquired variants in cancer is a paradigm of precision
      medicine, yet little has been reported about clinical laboratory practices across
      a broad range of laboratories. OBJECTIVE: - To use College of American
      Pathologists proficiency testing survey results to report on the results from
      surveys on next-generation sequencing-based oncology testing practices. DESIGN: -
      College of American Pathologists proficiency testing survey results from more
      than 250 laboratories currently performing molecular oncology testing were used
      to determine laboratory trends in next-generation sequencing-based oncology
      testing. RESULTS: - These presented data provide key information about the number
      of laboratories that currently offer or are planning to offer next-generation
      sequencing-based oncology testing. Furthermore, we present data from 60
      laboratories performing next-generation sequencing-based oncology testing
      regarding specimen requirements and assay characteristics. The findings indicate
      that most laboratories are performing tumor-only targeted sequencing to detect
      single-nucleotide variants and small insertions and deletions, using desktop
      sequencers and predesigned commercial kits. Despite these trends, a diversity of
      approaches to testing exists. CONCLUSIONS: - This information should be useful to
      further inform a variety of topics, including national discussions involving
      clinical laboratory quality systems, regulation and oversight of next-generation
      sequencing-based oncology testing, and precision oncology efforts in a data
      driven manner.

PMID- 29028369
TI  - Toll-like receptors: Significance, ligands, signaling pathways, and functions in
      mammals.
AB  - This review attempts to cover the implication of the toll-like receptors (TLRs)
      in controlling immune functions with emphasis on their significance, function,
      regulation and expression patterns. The tripartite TLRs are type I integral
      transmembrane receptors that are involved in recognition and conveying of
      pathogens to the immune system. These paralogs are located on cell surfaces or
      within endosomes. The TLRs are found to be functionally involved in the
      recognition of self and non-self-antigens, maturation of DCs and initiation of
      antigen-specific adaptive immune responses as they bridge the innate and adaptive
      immunity. Interestingly, they also have a significant role in immunotherapy and
      vaccination. Signals generated by TLRs are transduced through NFkappaB signaling
      and MAP kinases pathway to recruit pro-inflammatory cytokines and co-stimulatory
      molecules, which promote inflammatory responses. The excess production of these
      cytokines leads to grave systemic disorders like tumor growth and autoimmune
      disorders. Hence, regulation of the TLR signaling pathway is necessary to keep
      the host system safe. Many molecules like LPS, SOCS1, IRAK1, NFkappaB, and TRAF3
      are involved in modulating the TLR pathways to induce appropriate response.
      Though quantification of these TLRs helps in correlating the magnitude of immune
      response exhibited by the animal, there are several internal, external, genetic
      and animal factors that affect their expression patterns. So it can be concluded
      that any identification based on those expression profiles may lead to improper
      diagnosis during certain conditions.

PMID- 29028370
TI  - Is it Important to Talk About Technologies with Eating Disorder Clients? The
      Health-Care Professional Perspective.
AB  - Nowadays, the use of digital technology is an important issue that should be
      addressed during the treatment of people who have eating disorders. The
      involvement or absence of this issue reflects the understanding, experience, and
      atttude of health-care professionals toward their clients' use of technology. The
      aim of the present study was to investigate the perceptions of health-care
      professionals and their assessment of their clients' usage of digital technology
      while developing strategies for treatment. Semistructured interviews with 30
      professionals were performed from October 2015 to June 2016 and a thematic
      analysis was used to analyze the data. The health-care professionals' views could
      be summarized in three thematic groups: (1) technology use is not relevant for
      the cooperation; (2) technology use is relevant for the cooperation and addressed
      generally; and (3) technology use is relevant for the cooperation and addressed
      specifically. The results are discussed in relation to the theoretical model
      presented by Rodgers about the impact of technology on disordered eating
      behaviors and the implications for practice.

PMID- 29028371
TI  - From Social Media to Mainstream News: The Information Flow of the Vaccine-Autism
      Controversy in the US, Canada, and the UK.
AB  - Despite increasing warnings about inaccurate information online, little is known
      about how social media contribute to the widespread diffusion of unverified
      health information. This study addresses this issue by examining the vaccine
      autism controversy. By looking into a large dataset of Twitter, Reddit posts, and
      online news over 20 months in the US, Canada, and the UK, our time-series
      analysis shows that Twitter drives news agendas, and Reddit follows news agendas
      regarding the vaccine-autism debate. Additionally, the results show that both
      Twitter and Reddit are more likely to discuss the vaccine-autism link compared to
      online news content.

PMID- 29028372
TI  - The Effect of Latanaprost on Intraocular Inflammation and Macular Edema.
AB  - There is debate concerning whether the use of Latanoprost in early postoperative
      period of cataract surgery and in glaucoma patients with uveitis as it may
      aggravate the inflammation and results in macular edema (ME), because of blood
      ocular barrier disruption. However, there is no solid evidence for disruption of
      blood-ocular barrier with Latanoprost and aggravation of uveitis or ME formation.
      Similar to pseudophakic ME, the imaging ME in cases claimed to be secondary to
      Latanoprost is greater than clinical ME, happens mostly in complicated surgeries,
      and the vast majority resolve within weeks to months with using a non-steroidal
      anti-inflammatory drug. The current literature suggests that Latanoprost can be
      used in patients with uveitis and early after cataract surgery with or without
      concomitant topical non-steroidal anti-inflammatory drugs that are currently used
      by many ophthalmologists as a preventive measure for ME even in non-glaucoma
      uncomplicated cataract surgeries.

PMID- 29028373
TI  - Pulmonary Hypertension in Children.

PMID- 29028374
TI  - Recognizing Workplace Factors Contributing to Interstitial Lung Disease.

PMID- 29028376
TI  - Interprofessional Pulmocheck care pathway: An innovative approach to managing
      pediatric asthma care in the Netherlands.
AB  - OBJECTIVES: Under-diagnosis and suboptimal asthma control in children persists.
      An innovative care pathway was developed by a hospital department of pediatrics
      with the aim to detect pulmonary problems in children and provide appropriate
      treatment possibilities through systematic feedback towards the referring primary
      care physician. Primary care physicians can use this pathway to refer children
      with asthma-like symptoms for a one-day assessment. Goals are to measure the
      usage of the pathway by primary care general practitioners (GPs), the outcomes in
      terms of new diagnoses of asthma, the reduction in regular referrals, generated
      recommendations/therapy and the adequacy of asthma follow-up. METHODS: We
      collected all feedback letters sent to the GP concerning children who underwent
      the Pulmocheck in 2010, 2011 and 2012. Furthermore, all GPs, who had referred a
      child to the Pulmocheck in this period and that subsequently was diagnosed with
      asthma and was further managed in primary care, were sent a follow-up
      questionnaire in 2014. RESULTS: There were 121 referrals from 51 GPs in 3 years
      to this pathway. In 59.5% of these referrals a new diagnosis of asthma was
      established. In 90.9% one or more changes in clinical management were advised.
      The response rate to the follow-up questionnaires was 65.7% of which 4.8% of the
      children with new established asthma were reviewed four times or more in the
      follow-up period, 17.4% two times, 65.2% once, and in 8.7% were not followed.
      CONCLUSIONS: The specialty pediatric asthma care pathway revealed a high number
      of children with newly diagnosed asthma, but was also helpful to exclude this
      diagnosis. However, the referral rate of GPs to this pathway was low, but in the
      children, that were referred several changes in the clinical management were
      advised and the frequency of monitoring of the children with diagnosed asthma was
      not in accordance with the asthma guidelines.

PMID- 29028375
TI  - Health Disparities in Patients with Pulmonary Arterial Hypertension: A Blueprint
      for Action. An Official American Thoracic Society Statement.
AB  - BACKGROUND: Health disparities have a major impact in the quality of life and
      clinical care received by minorities in the United States. Pulmonary arterial
      hypertension (PAH) is a rare cardiopulmonary disorder that affects children and
      adults and that, if untreated, results in premature death. The impact of health
      disparities in the diagnosis, treatment, and clinical outcome of patients with
      PAH has not been systematically investigated. OBJECTIVES: The specific goals of
      this research statement were to conduct a critical review of the literature
      concerning health disparities in PAH, identify major research gaps and prioritize
      direction for future research. METHODS: Literature searches from multiple
      reference databases were performed using medical subject headings and text words
      for pulmonary hypertension and health disparities. Members of the committee
      discussed the evidence and provided recommendations for future research. RESULTS:
      Few studies were found discussing the impact of health disparities in PAH. Using
      recent research statements focused on health disparities, the group identified
      six major study topics that would help address the contribution of health
      disparities to PAH. Representative studies in each topic were discussed and
      specific recommendations were made by the group concerning the most urgent
      questions to address in future research studies. CONCLUSIONS: At present, there
      are few studies that address health disparities in PAH. Given the potential
      adverse impact of health disparities, we recommend that research efforts be
      undertaken to address the topics discussed in the document. Awareness of health
      disparities will likely improve advocacy efforts, public health policy and the
      quality of care of vulnerable populations with PAH.

PMID- 29028377
TI  - Randomized trial of electrodynamic microneedle combined with 5% minoxidil topical
      solution for the treatment of Chinese male Androgenetic alopecia.
AB  - BACKGROUND: In treating androgenetic alopecia, 5% minoxidil is a commonly used
      topical drug. By using electrodynamic microneedle at the same time may increase
      absorption of minoxidil and further stimulate hair growth. OBJECTIVE: A 24-week,
      randomized, evaluator blinded, comparative study was performed to evaluate the
      efficacy of treating Chinese male androgenetic alopecia using microneedle
      combined with 5% minoxidil topical solution. METHODS: Randomized subjects
      received topical 5% minoxidil (group 1, n = 20), local electrodynamic microneedle
      treatments (group 2, n = 20), or local electrodynamic microneedle treatments plus
      topical 5% minoxidil (group 3, n = 20). A total of 12 microneedle treatments were
      performed every 2 weeks with 2ml 5% minoxidil delivery in group 3 during each
      microneedle treatment. Patient receiving topical 5% minoxidil applied 1 ml of the
      solution twice daily over the course of the study. A total of 60 Chinese male
      subjects with Norwood-Hamilton type III-VI androgenetic alopecia were treated.
      RESULTS: The mean improvement in total hair density from baseline to 24 weeks was
      18.8/cm2 in group 1, 23.4/cm2 in group 2, and 38.3/cm2 in group 3. The hair
      growth in the 3 groups was significantly different (P = 0.002), but there were no
      significant differences in toxicity found between the 3 groups. CONCLUSIONS:
      Treatment with microneedle plus topical 5% minoxidil was associated with the best
      hair growth.

PMID- 29028378
TI  - From the Editor-in-Chief's Desk.

PMID- 29028380
TI  - Electrospray ionization mass spectrometric study of thallium complexes with
      nucleosides.
AB  - The complexes between Tl+, K+, and nucleosides were studied by using electrospray
      ionization mass spectrometry. It was found that for complexes of 1:1
      stoichiometry, thallium complexes with cytidine were the most abundant and
      thallium complexes with guanosine were the second most abundant ones. The
      relative abundances of cytidine-Tl+ to cytidine-K+ complexes depended on
      stoichiometry (at higher stoichiometry the potassium complexes were more
      abundant). In other words, the relative affinity of Tl+ and K+ to form cytidine
      complexes depends on the stoichiometry of the formed complexes. Guanosine-Tl+
      complexes were more abundant than guanosine-K+ complexes, irrespective of
      stoichiometry. Both guanosine tetramer and mixed cytidine/guanosine tetramer were
      more abundant when they were stabilized by thallium than potassium. Therefore,
      Tl+ may affect the K+ stabilization of these tetramers.

PMID- 29028381
TI  - Dependence of matrix effect on ionization polarity during LC-ESI-MS analysis of
      derivatized amino acids in some natural samples.
AB  - Matrix effect, the influence of co-eluting components on the ionization
      efficiency of the analyte, affects the trueness and precision of the LC-ESI-MS
      analysis. Derivatization can reduce or eliminate matrix effect, for example,
      diethyl ethoxymethylenemalonate (DEEMM) derivatives have shown less matrix effect
      compared to other derivatives. Moreover, the use of negative ion mode can further
      reduce matrix effect. In order to investigate the combination of derivatization
      and different ionization modes, an LC-ESI-MS/MS method using alternating
      positive/negative ion mode was developed and validated. The analyses in positive
      and negative ion modes had comparable limit of quantitation values. The influence
      of ESI polarity on matrix effect was investigated during the analysis of 22 DEEMM
      derivatized amino acids in herbal extracts and honeys. Sample dilution approach
      was used for the evaluation of the presence of matrix effect. Altogether, 4
      honeys and 11 herbal extracts were analyzed, and the concentrations of 22 amino
      acids in the samples are presented. In the positive ion mode, matrix effect was
      observed for several amino acid derivatives and the matrix effect was stronger in
      honey samples compared to the herbal extracts. The negative ion mode was free
      from matrix effect, with only few exceptions in honeys (average relative standard
      deviation over all analytes and matrices was 8%; SD = 7%). The matrix effect was
      eliminated in the positive ion mode by sample dilution and agreement between
      concentrations from the two ion modes was achieved for most amino acids. In
      conclusion, it was shown that the combination of derivatization and negative ion
      mode can be a powerful tool for minimizing matrix effect in more complicated
      applications.

PMID- 29028382
TI  - Simultaneous determination of metolazone and valsartan in plasma by on-line SPE
      coupled with liquid chromatography/tandem mass spectrometry.
AB  - Combination of metolazone (0.5 mg) and valsartan (80 mg) has been verified as a
      promising therapy treatment for hypertension. In order to facilitate to
      pharmacokinetic research, it needs a method for the simultaneously determination
      of metolazone and valsartan in biological samples. However, there are no relative
      reports so far. In order to facilitate to pharmacokinetic research, an on-line
      solid phase extraction coupled with liquid chromatography-tandem mass
      spectrometry method for the simultaneous determination of metolazone and
      valsartan in beagle dog plasma was developed and validated in this study. An on
      line solid phase extraction column Retain PEP Javelin (10 mm * 2.1 mm) was used
      to remove impurities in plasma samples. The metolazone, valsartan and internal
      standard (losartan) were separated on a Poroshell 120 SB-C18 column (4.6 mm * 50
      mm * 2.7 um) with a gradient elution procedure. Acidified acetonitrile/water
      mixture was used as a mobile phase. The selected multiple-reaction monitoring
      mode in positive ion was performed and the parent to the product transitions m/z
      366/259, m/z 436.2/291 and m/z 423.4/207 were used to measure the metolazone,
      valsartan and losartan. The method was linear over the range of 0.1-100 ng/mL and
      1-1000 ng/mL for metolazone and valsartan, respectively. This method was
      validated in terms of specificity, linearity, sensitivity, precision, accuracy,
      matrix effect, and stability and then successfully applied to pharmacokinetic
      studies of the metolazone and valsartan combination tablets in beagle dogs.

PMID- 29028384
TI  - Effect of metal surfaces on matrix-assisted laser desorption/ionization analyte
      peak intensities.
AB  - Different metal surfaces in the form of transmission electron microscope grids
      were examined as support surfaces in matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry with a view towards enhancement of peptide
      signal intensity. The observed enhancement between 5-fold and 20-fold relative to
      the normal stainless steel slide was investigated by applying the thermal
      desorption model for matrix-assisted laser desorption/ionization. A simple model
      evaluates the impact that the thermal properties of the metals have on the ion
      yield of the analyte. It was observed that there was not a direct, or strong,
      correlation between the thermal properties of the metals and the corresponding
      ion yield of the peptides. The effects of both fixed and variable laser
      irradiances versus ion yield were also examined for the respective metals
      studied. In all cases the use of transmission electron microscope grids required
      much lower laser irradiances in order to generate similar peak intensities as
      those observed with a stainless steel surface.

PMID- 29028383
TI  - Rapid detection of undesired cosmetic ingredients by matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry.
AB  - In recent years, cosmetic industry profits soared due to the widespread use of
      cosmetics, which resulted in illicit manufacturers and products of poor quality.
      Therefore, the rapid and accurate detection of the composition of cosmetics has
      become crucial. At present, numerous methods, such as gas chromatography and
      liquid chromatography-mass spectrometry, were available for the analysis of
      cosmetic ingredients. However, these methods present several limitations, such as
      failure to perform comprehensive and rapid analysis of the samples. Compared with
      other techniques, matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry offered the advantages of wide detection range, fast speed and high
      accuracy. In this article, we briefly summarized how to select a suitable matrix
      and adjust the appropriate laser energy. We also discussed the rapid
      identification of undesired ingredients, focusing on antibiotics and hormones in
      cosmetics.

PMID- 29028385
TI  - Computation of stability regions for the cylindrical ion trap with no octupole
      electric field as compared to the corresponding results of the Paul trap.
AB  - The cylindrical ion trap is analyzed so that the octupole component of the
      electric field inside the trap is set to zero. As a consequence, the diameter to
      height ratio is computed to be 1.20 for which the quadrupole component of the
      cylindrical ion trap is dominant. Afterwards, it is concluded that the electric
      potential inside the trap as well as the corresponding stability regions are very
      similar to those obtained for an ideal Paul trap with pure quadrupole electric
      field. Furthermore, we drew a conclusion that the stability diagrams of the
      cylindrical ion trap without octupole term and the stability diagrams of the Paul
      trap have 5.6%, 3.7%, and 2.9% discrepancy for the first, second, and third
      stability diagrams, respectively. It should be noted that, expansion of the
      electric potential inside the cylindrical ion trap in terms of the multipole
      electric field components and making the advantages of the octupole term
      elimination has not been reported in the literature previously.

PMID- 29028386
TI  - Applications of the fractional calculus to study the physical theory of ion
      motion in a quadrupole ion trap.
AB  - In this article, fractional calculus has been applied to study the motion of ions
      in a three-dimensional radio frequency quadrupole ion trap; we have called this
      arrangement a fractional quadrupole ion trap. The main purpose of the article is
      to show that by controlling the fractional parameter of a trapped ion, one can
      gain a more efficient mass separation. In what follows, we will see that with
      decreasing the fractional parameter, we can achieve a smaller first stability
      region. Note that a small stability diagram will result in a good and acceptable
      mass separation. Various methods can be proposed to obtain a desired ion
      acceleration with a sufficient accuracy for good mass separation, which is
      similar to the one obtained by a fractional ion trap. Some of these methods are
      using the effects of a damping force, a magnetic field or both on the confinement
      of particles in the quadrupole ion trap. The first stability regions are plotted
      for all of the aforementioned methods, and simulation results are provided to
      compare them with those for the fractional case.

PMID- 29028387
TI  - Two possible improvements for mass spectrometry analysis of intact biomolecules.
AB  - The goals of our study were to investigate abilities of two approaches to
      eliminate possible errors in electrospray mass spectrometry measurements of
      biomolecules. Passing of a relatively dense supersonic gas jet through ionization
      region followed by its hitting the spray of the analyzed solution in low vacuum
      may be effective to keep an initial biomolecule structure in solution. Provided
      that retention of charge carriers for some sites in the biomolecule cannot be
      changed noticeably in electrospray ion source, decomposition and separation of
      charge-state distributions of electrosprayed ions may give additional information
      about native structure of biomolecules in solution.

PMID- 29028388
TI  - Feature selection algorithm for spray-from-tissue mass spectrometry.
AB  - Detection of the brain tumor margins is one of the most significant problems in
      neurosurgery. Several mass spectrometry-based approaches have been proposed
      recently for tumor boundary detection. One of them, spray from tissue does not
      require sample preparation but needs special algorithms for analysis of its
      spectra. Here we proposed the feature selection algorithm designed for analysis
      of spray-from-tissue data.

PMID- 29028389
TI  - Investigation of the ozonation products of natural complex mixtures using Fourier
      transform ion cyclotron resonance mass spectrometry.
AB  - Natural complex mixtures such as oil and dissolved organic matter play an
      important role in the economy and in the global carbon cycle. One of the most
      promising approaches for the investigation of the chemical structure of such
      substances is the combination of the high-resolution mass spectrometry and
      selective chemical reactions. Here, we report the investigation of the ozonation
      products of natural complex mixtures using Fourier transform ion cyclotron
      resonance mass spectrometry. Ozonation of crude oil results in the appearance of
      the new compounds with high content (up to 9 atom) of oxygen. Isotopic exchange
      reaction showed that those oxygen stem from the carbonyl groups. Ozonation of the
      dissolved organic matter leads to the destruction of the substance and shift
      towards the region of the saturated compounds.

PMID- 29028390
TI  - High-resolution mass spectra processing for the identification of different
      pathological tissue types of brain tumors.
AB  - The purpose of the work is to demonstrate the possibilities of identifying the
      different types of pathological tissue identification directly through tissue
      mass spectrometry. Glioblastoma parts dissected during neurosurgical operation
      were investigated. Tumor fragments were investigated by the immunohistochemistry
      method and were identified as necrotic tissue with necrotized vessels, necrotic
      tissue with tumor stain, tumor with necrosis (tumor tissue as major), tumor,
      necrotized tumor (necrotic tissues as major), parts of tumor cells, boundary
      brain tissue, and brain tissue hyperplasia. The technique of classification of
      tumor tissues based on mass spectrometric profile data processing is suggested in
      this paper. Classifiers dividing the researched sample to the corresponding
      tissue type were created as a result of the processing. Classifiers of necrotic
      and tumor tissues are shown to yield a combined result when the tissue is
      heterogeneous and consists of both tumor cells and necrotic tissue.

PMID- 29028391
TI  - A new approach to improving the accuracy of elemental analysis in laser mass
      spectrometry.
AB  - It is shown that the main reason affecting the accuracy and reproducibility of
      the elemental analysis of solids with a laser source of ions is the difference in
      the ionization cross sections of different elements in the generation of laser
      plasma. Computer modeling was carried out for the evaporation of the sample and
      generation of laser plasma at different values of laser power density. The aim of
      modelling was to determine the cause of the low accuracy of analysis by direct
      selection of ions from the plasma. The researches have shown that we cannot get
      satisfactory accuracy of analysis using analytical signal formed only on the base
      of single-charged ions. At the same time, in the formation of an analytical
      signal, as a sum of the intensities of the mass peaks of all charges of each
      element, the accuracy of the analysis does not depend either on the ionization
      cross section or on the nonreproducibility of the laser radiation power. It is
      shown that this approach completely eliminates the "matrix effect."

PMID- 29028392
TI  - Application of selected reaction monitoring and parallel reaction monitoring for
      investigation of HL-60 cell line differentiation.
AB  - Targeted mass spectrometry represents a powerful tool for investigation of
      biological processes. The convenient approach of selected reaction monitoring
      using stable isotope-labeled peptide standard (SIS) is widely applied for protein
      quantification. Along with this method, high-resolution parallel reaction
      monitoring has been increasingly used for protein targeted analysis. Here we
      applied two targeted approaches (selected reaction monitoring with SIS and label
      free parallel reaction monitoring) to investigate expression of 11 proteins
      during all-trans retinoic acid-induced differentiation of HL-60 cells. In our
      experiments, we have determined the proteins expression ratio at 3, 24, 48, and
      96 h after all-trans retinoic acid treatment in comparison with 0 h,
      respectively. Expression profiles of four proteins (VAV1, PRAM1, LYN, and CEBPB)
      were highly correlated ( r > 0.75) and FGR expression was detected on proteome
      level starting from 24 h by both techniques. For prominent differences (fold
      change >= 2) label-free parallel reaction monitoring is not inferior to selected
      reaction monitoring with isotopically labeled peptide standards. Differentially
      expressed proteins, that have been determined in our study, can be considered as
      potential drug targets for acute myeloid leukemia (AML) treatment.

PMID- 29028393
TI  - Editorial.

PMID- 29028394
TI  - Active sampling system for gas-phase analyzers.
AB  - The approaches for increasing a contact-free sampling distance up to 40 cm for a
      field asymmetric ion mobility spectrometer were investigated and implemented by
      use both the vortex flow made by a rotating impeller and the laser desorption of
      traces of low volatile explosives. The sampling device for a laser-based field
      asymmetric ion mobility spectrometer including a high-speed rotating impeller was
      designed and built with help of computer simulation of vortex and analytical
      flows. The dependence of a signal of trinitrotoluene vapors on a rotational speed
      of an impeller was obtained. The optimization of analytical flow was performed.
      The effective sampling distance is increased up to 28 cm for trinitrotoulene
      vapors detection by a field asymmetric ion mobility spectrometer equipped with a
      rotating impeller. The distance can be increased up to 40 cm using laser
      irradiation of objects with traces of explosives. It was shown that under ambient
      conditions the efficient desorption of low-volatile explosives is achieved at
      laser intensity 107 W/cm2, wavelength lambda = 266 nm, pulse energy about 1 mJ
      and pulse frequency not less than 10 Hz.

PMID- 29028395
TI  - Mass selective laser cooling of 229Th3+ in a multisectional linear Paul trap
      loaded with a mixture of thorium isotopes.
AB  - We consider an experiment on trapping and laser cooling of 229Th3+ ions in a
      linear Paul trap in the presence of undesirable impurities such as ions of the
      radioactive isotope 228Th3+. We suggest a method of separating these impurities
      by means of selective laser cooling utilizing the isotope shift of cooling
      transitions in 229Th3+ and 228Th3+ ions. According to our estimation, the isotope
      shift is equal to 3.4 GHZ and makes laser separation of these isotopes possible.

PMID- 29028396
TI  - Laser-stimulated desorption of organic molecules from surfaces, as a method of
      increasing the efficiency of ion mobility spectrometry analysis.
AB  - Application of laser-induced desorption was investigated as a method of
      increasing the efficiency of gas phase analyzers on principles of field
      asymmetric ion mobility spectrometry. Mass spectrometric data of investigations
      of laser desorption of pentaerythritoltetranitrate molecules and
      cyclotetramethylenetetranitramine molecules from quartz substrate under vacuum
      were obtained. Laser sources a Nd3+:YAG with nanosecond pulse duration (lambda =
      532 nm) and a continuous wave diode laser (lambda = 440 nm) were used. It was
      shown that both laser sources have different desorption abilities. This is
      expressed in various time of appearance of desorbed products that is caused by
      different heating mechanisms of surface layer. The desorbed quantity under action
      of both laser sources exceeds the detection threshold for all modern gas phase
      analyzers. It should be noted that despite the presence of surface dissociation
      of explosives under laser radiation, the quantity of nondissociated molecules is
      large enough for detection by ion mobility and field asymmetric ion mobility
      spectrometers. The optimal parameters of laser radiation for effective removal
      (evaporation) molecules of low-volatile compounds from surfaces are defined. The
      conclusion about preferable use of a Nd3+:YAG laser for increasing the detection
      ability of detectors based on ion mobility spectrometry was made.

PMID- 29028397
TI  - Detection of gas traces using semiconductor sensors, ion mobility spectrometry,
      and mass spectrometry.
AB  - This article deals with the state-of-the-art instrumentation and application in
      the field of solid state gas sensorics, ion mobility spectrometry and mass
      spectrometry-related research for the detection and measurements of low gas and
      vapor concentrations. The advantages and disadvantages of gas-analytical devices
      and systems are discussed, as well as the possibilities of its complex and/or
      complementary applications. Ion mobility spectrometry-mass spectrometry and
      subsequent techniques based on solid-state gas sensors are proposed for planned
      medical study.

PMID- 29028398
TI  - A computer model of comprehensive modeling of the laser time-of-flight analyzer.
AB  - This article offers a new approach to computer modeling of time-of-flight
      analyzers of mass spectrometers. The main feature of the model is comprehensive
      tracking of the processes from the laser plasma generation until the final stage,
      on which the isotopic or elemental composition is determined for the analyzed
      solid sample. Apart from usual models based on SIMION-8 3D or similar software,
      this article proposes fundamentally new modeling stages. These stages are (1)
      generation and spread of laser plasma, (2) formation of the ion packages, (3) ion
      detection, and (4) formation and processing of the analytical signals. In order
      to provide consistent modeling of all the stages, special software units were
      developed. Program control of the analyzer ion optics (electrodes voltages)
      allows scan of mass spectra by ion energy. Additional complex of the programs
      provides simulation of mass spectra digitization, summation of digitized mass
      spectra for a wide range of variable parameters, and consideration of the
      discriminatory effects. According to the data, the software calculates ion
      optical characteristics of the analyzer and the analytical parameters of
      measurement results.

PMID- 29028399
TI  - Is myelin basic protein a potential biomarker of brain cancer?
AB  - Myelin basic protein is a potential biomarker for the central nervous system
      diseases in which the myelin sheath is destroyed. Using pseudo-selected reaction
      monitoring and the method of standard additions, we have measured the myelin
      basic protein level in the cerebrospinal fluid of patients with neurotrauma (n =
      6), chronic neurodegenerative diseases (n = 2) and brain cancer (n = 5). Myelin
      basic protein was detected only in four out of five cerebrospinal fluid samples
      of patients with brain cancer. The cerebrospinal fluid myelin basic protein level
      ranged from 3.7 to 8.8 ng ml-1. We suggest that monitoring of myelin basic
      protein in cerebrospinal fluid can serve as a diagnostic test for the brain
      cancer.

PMID- 29028400
TI  - Label-free study of cosmonaut's urinary proteome changes after long-duration
      spaceflights.
AB  - During the entire time that cosmonauts stay on board the international space
      station, different extreme space flight factors affect their bodies. In order to
      find out what physiological changes occur under the influence of spaceflight,
      different parameters of the human body before and after flights are monitored.
      Analysis of the urine proteome is one of the most perspective non-invasive
      methods of condition monitoring. The aim of the study was to perform a
      comparative semi-quantitative label-free urine proteome analysis of samples
      collected from 21 cosmonauts before and after long-duration spaceflight at the
      international space station. For proteomic analysis, urine samples were collected
      from cosmonauts at three time periods: six months prior to the flight as a
      background, and on days 1 and 7 of the recovery period after landing. All probes
      were analyzed by LC-MS/MS, and 256 proteins were identified with more than one
      unique peptide. The core proteome consists of 50 proteins that are detected in
      more than 70% of the samples. Label-free semi-quantitative analysis enables us to
      find 20 proteins which were significantly changed on +1 day and +7 day with
      respect to background. Most of these proteins participate in the regulation of
      biological processes, in the regulation of the immune system and in intracellular
      processes also; some of these proteins are related with stress and response to
      stimulus. In conclusion, the proteomic analysis of cosmonauts' urine samples
      provides new data on the human body's adaptation to ground conditions after long
      duration spaceflight.

PMID- 29028401
TI  - Numerical simulation of ion transport in an atmosphere-to-vacuum interface taking
      into account gas dynamics and space charge.
AB  - A two-step approach was developed for the study of ion transport in an
      atmospheric pressure interface. In the first step, the flow in the interface was
      numerically simulated using the standard gas dynamic package ANSYS CFX 15.0. In
      the second step, the calculated fields of pressure, temperature, and velocity
      were imported into a custom-built software application for simulation of ion
      motion under the influence of both gas dynamic and electrostatic forces. To
      account for space charge effects in axially symmetric interfaces an analytical
      expression was used for the Coulomb force. For all other types of interfaces, an
      iterative approach for the Coulomb force computation was developed. The
      simulations show that the influence of the space charge is the main contributor
      to the loss of ion current in the heated capillary. In addition, the maximum ion
      current which can be transmitted through the heated capillary (0.58 mm inner
      diameter and 58.5 mm length) is limited to ~6 nA for ions with m/z = 508 Da and
      with reduced ion mobility 1.05 cm2V-1s-1. This limit remains practically constant
      and independent of the ion current at the entrance of the capillary. For a
      particular ion type, this limit depends on its m/z ratio and ion mobility.

PMID- 29028402
TI  - Effect of ion clouds micromotion on measured signal in Fourier transform ion
      cyclotron resonance: Computer simulation.
AB  - Particle-in-cell-based realistic simulation of Fourier transform ion cyclotron
      resonance experiments could be used to generate ion trajectories and a signal
      induced on the detection electrodes. It has been shown recently that there is a
      modulation of "reduced" cyclotron frequencies in ion cyclotron resonance signal
      caused by Coulomb interaction of ion clouds. In this work it was proposed to use
      this modulation in order to determine frequency difference between an ion of
      known m/z and all other ions generating signal in ion cyclotron resonance cell.
      It is shown that with an increase of number of ions in ion cyclotron resonance
      trap, the modulation index increases, which lead to a decrease in the accuracy of
      determination of peak intensities by super Fourier transform resolution methods
      such as filter diagonalization method.

PMID- 29028403
TI  - Laser ion mobility spectrometry in the detection of ultra-low quantities of
      explosives.
AB  - The paper presents the results of research and development of ion mobility
      spectrometer with laser ion sources for detecting ultra-low quantities of
      explosives in air. Particular attention is paid to the mechanisms of the
      formation of negative ions. It is shown that laser ionization with respect to ion
      mobility spectrometry provides an increase of sensitivity and selectivity of
      detection. The ion mobility spectra of the most common nitro explosives are
      investigated. The detection threshold for laser ion mobility spectrometer was
      reached at the level of 10-14 g/cm3 (for trinitrotoluene).

PMID- 29028404
TI  - Static harmonization of dynamically harmonized Fourier transform ion cyclotron
      resonance cell.
AB  - Static harmonization in the Fourier transform ion cyclotron resonance cell
      improves the resolving power of the cell and prevents dephasing of the ion cloud
      in the case of any trajectory of the charged particle, not necessarily
      axisymmetric cyclotron (as opposed to dynamic harmonization). We reveal that the
      Fourier transform ion cyclotron resonance cell with dynamic harmonization
      (paracell) is proved to be statically harmonized. The volume of the statically
      harmonized potential distribution increases with an increase in the number of
      trap segments.

PMID- 29028405
TI  - Evaluation of plasma peptides extraction methods by high-resolution mass
      spectrometry.
AB  - Monitoring of peptides offers a promising approach for the discovery of novel
      biomarkers, which might be valuable for detection, treatment and prevention of
      large variety of diseases. Development of highly effective methods for plasma
      peptide extraction remains an important task. In the current study, we applied
      different types of plasma peptide extraction approaches to reveal efficient
      methods which would provide the highest peptide yield. We used different
      combinations of plasma treatment with acetonitrile and/or urea/guanidine, protein
      precipitation by acetone, gel-filtration, ultrafiltration, and two types of solid
      phase extraction. The extracted peptides were analyzed by LC-MS/MS. The obtained
      results suggest that several methods, including differential solubilization,
      organic precipitation, as well as some variants of ultrafiltration and solid
      phase extraction, provide effective plasma peptide enrichment convenient for
      further LC-MS/MS analysis. Alas, most of the identified peptides were extracted
      by only one of the applied methods. Hence, it seems reasonable to consider
      several methods to increase the possibility of novel biomarker discovery.

PMID- 29028406
TI  - Loading of mass spectrometry ion trap with Th ions by laser ablation for nuclear
      frequency standard application.
AB  - We describe an original multisectional quadrupole ion trap aimed to realize
      nuclear frequency standard based on the unique isomer transition in thorium
      nucleus. It is shown that the system effectively operates on Th+, Th2+ and Th3+
      ions produced by laser ablation of metallic thorium-232 target. Laser intensity
      used for ablation is about 6 GW/cm2. Via applying a bias potential to every
      control voltage including the RF one, we are able not only to manipulate ions
      within the energy range as wide as 1-500 eV but to specially adjust trap
      potentials in order to work mainly with ions that belong to energy distribution
      maximum and therefore to effectively enhance the number of trapped ions.
      Measurement of energy distributions of 232Th+, 232Th2+, 232Th3+ ions obtained by
      laser ablation allows us to define optimal potential values for trapping process.
      Observed number of ions inside trap in dependence on trapping time is found to
      obey an unusually slow - logarithmic decay law that needs more careful study.

PMID- 29028407
TI  - Synthesis of carboxylated styrene polymer for internal calibration of Fourier
      transform ion cyclotron resonance mass-spectrometry of humic substances.
AB  - We report synthesis and application of the novel carboxylated styrene for
      internal calibration of Fourier transform ion cyclotron resonance mass-spectra of
      humic substances. The calibrant was synthesized in five steps from
      acetylsalicylic acid (aspirin) followed by spontaneous polymerization of vinyl
      salicylic acid. Aromatic nature of the prepared polymer enabled its simultaneous
      analysis in the presence of the Suwannee River fulvic acid without using dual
      spray approach. The major advantage of the calibrant proposed in this study is a
      lack of suppression of humic substances signals and maintenance of peak intensity
      distribution. The appropriate calibration resulted in an increased number of
      unambiguous identification in Suwannee River fulvic acid. Thanks to the higher
      mass accuracy, it was also possible to refine attribution of the CHOS species to
      hydrolysable tannins as opposed to the erroneous previous assignment to the
      condensed tannins.

PMID- 29028408
TI  - Tonic Pupil in Cytomegalovirus Anterior Uveitis in an Immunocompetent Adult Male 
      A Case Report.
AB  - PURPOSE: To report an interesting case of development of tonic pupil in an
      immunocompetent male with cytomegalovirus (CMV) anterior uveitis. METHODS:
      Retrospective case report Results: A 30-year-old Iranian healthy male was
      diagnosed to have Posner-Schlossman syndrome (OS). Aqueous tap was positive for
      CMV by multiplex Polymerase chain reaction (PCR). Adequate control of
      inflammation and Intraocular pressures (IOP) were achieved with topical steroids,
      ganciclovir gel, and antiglaucoma medications. On a follow-up visit, he
      complained of recent onset of blurring of vision (OS) despite appropriate
      refractive correction, quiet anterior chamber, and normal IOP. Pupillary
      examination showed anisocoria (larger pupil in OS). Pupillary constriction (OS)
      on instillation of 0.125% pilocarpine drops confirmed the diagnosis of a tonic
      pupil. CONCLUSION: We describe a unique finding of tonic pupil on a follow-up
      examination in an immunocompetent adult male with CMV anterior uveitis. A prior
      association has not been described in literature (Medline Search).

PMID- 29028409
TI  - High prevalence and low intensity Ichthyophonus infections in Pacific Halibut
      (Hippoglossus stenolepis).
AB  - Ichthyophonus occurred at high prevalence but low intensity in Pacific Halibut
      (Hippoglossus stenolepis) throughout the west coast of North America, ranging
      from coastal Oregon to the Bering Sea. Infection prevalence in adults was
      variable on spatial and temporal scales, with the lowest prevalence typically
      occurring on the edges of the geographic range and highest prevalence
      consistently occurring inside Prince William Sound, AK (58-77%). Additionally,
      intra-annual differences occurred at Albatross - Portlock, AK (71% versus 32%
      within 2012) and inter-annual differences occurred along coastal Oregon (50%
      versus 12% from 2012 to 2015). The infection prevalence was influenced by host
      age, increasing from <= 3% among the youngest cohorts (<=age 6) to 39-54% among
      age 9-17 cohorts, then decreasing to 27% among the oldest (age 18+) cohorts.
      There was little indication of significant disease impacts to Pacific Halibut, as
      the intensity of infection was uniformly low and length-at-age was similar
      between infected and uninfected cohorts. These results suggest that Ichthyophonus
      in Pacific Halibut currently represents a stable parasite-host paradigm in the
      North Pacific. Received 04 May 2017 accepted 09 Oct 2017 revised 21 Sep 2017.

PMID- 29028410
TI  - Development of an Inhibitor Screening Assay for Mono-ADP-Ribosyl Hydrolyzing
      Macrodomains Using AlphaScreen Technology.
AB  - Protein mono-ADP-ribosylation is a posttranslational modification involved in the
      regulation of several cellular signaling pathways. Cellular ADP-ribosylation is
      regulated by ADP-ribose hydrolases via a hydrolysis of the protein-linked ADP
      ribose. Most of the ADP-ribose hydrolases share a macrodomain fold. Macrodomains
      have been linked to several diseases, such as cancer, but their cellular roles
      are mostly unknown. Currently, there are no inhibitors available targeting the
      mono-ADP-ribose hydrolyzing macrodomains. We have developed a robust AlphaScreen
      assay for the screening of inhibitors against macrodomains having mono-ADP-ribose
      hydrolysis activity. We utilized this assay for validatory screening against
      human MacroD1 and identified five compounds inhibiting the macrodomain. Dose
      response measurements and an orthogonal assay further validated four of these
      compounds as MacroD1 inhibitors. The developed assay is homogenous, easy to
      execute, and suitable for the screening of large compound libraries. The assay
      principle can also be adapted for other ADP-ribose hydrolyzing macrodomains,
      which can utilize a biotin-mono-ADP-ribosylated protein as a substrate.

PMID- 29028412
TI  - The Bacteroid Periplasm in Soybean Nodules Is an Interkingdom Symbiotic Space.
AB  - The functional role of the periplasm of nitrogen-fixing bacteroids has not been
      determined. Proteins were isolated from the periplasm and cytoplasm of
      Bradyrhizobium diazoefficiens bacteroids and were analyzed using liquid
      chromatography tandem mass spectrometry proteomics. Identification of bacteroid
      periplasmic proteins was aided by periplasm prediction programs. Approximately
      40% of all the proteins identified as periplasmic in the B. diazoefficiens genome
      were found expressed in the bacteroid form of the bacteria, indicating the
      periplasm is a metabolically active symbiotic space. The bacteroid periplasm
      possesses many fatty acid metabolic enzymes, which was in contrast to the
      bacteroid cytoplasm. Amino acid analysis of the periplasm revealed an abundance
      of phosphoserine, phosphoethanolamine, and glycine, which are metabolites of
      phospholipid metabolism. These results suggest the periplasm is a unique space
      and not a continuum with the peribacteroid space. A number of plant proteins were
      found in the periplasm fraction, which suggested contamination. However,
      antibodies to two of the identified plant proteins, histone H2A and lipoxygenase,
      yielded immunogold labeling that demonstrated the plant proteins were
      specifically targeted to the bacteroids. This suggests that the periplasm is an
      interkingdom symbiotic space containing proteins from both the bacteroid and the
      plant.

PMID- 29028413
TI  - Initial Assessment, Treatment, and Follow-Up of Minor Pediatric Burn Wounds in
      Four Patients Remotely: A Preliminary Communication.
AB  - BACKGROUND: Close, multidisciplinary collaboration with burn experts is the
      essential strategy to achieve the best functional and esthetic outcomes in burn
      wound treatment. Management of minor burn injuries, where no specialized care is
      available, might be challenging. One concept to achieve a fast and timely result
      is the application of telemedicine. The objective of this study was to assess and
      develop a simple telemedicine protocol, which can be applied globally. MATERIAL
      AND METHODS: We present a pilot study based on a pediatric population of four
      patients with minor burns. Based on the severity and burn area, two cases of
      ambulant pediatric patients (mean 1% total body surface area, superficial and
      deep 2 degrees  burn) with minor burn injuries met study criteria and were
      enrolled. A pediatrician performed the initial assessment, followed by plastic
      surgery video consultation, using telephone's digital camera. Treatment protocols
      were designed to optimize outcomes. After the initial treatment phase, which took
      place at a nonteaching local hospital in Poland from January 1, 2014, to December
      31, 2014, clinical follow-up was performed by a plastic surgeon via smartphone in
      the United States. RESULTS: We have achieved complete burn wound resolution, in
      all patients, with no scarring and only minor discoloration. A simple,
      reproducible treatment protocol was designed to include dressing changes and
      additional outpatient visits. CONCLUSIONS: Implementation of a telemedicine
      protocol allows for easy access to burn consultations, helps multidisciplinary
      collaboration, eases follow-ups, and shortens specialists' consult wait times.
      Real-time evaluation provides fast and flexible treatment, without long distance
      travels, for patients and their families. Telemedicine increases the frequency of
      follow-up, contributes to the esthetic outcome, and together with improved cost
      effectiveness is beneficial for both the patient and healthcare system.

PMID- 29028411
TI  - Expanding the map of protein-RNA interaction sites via cell fusion followed by
      PAR-CLIP.
AB  - PAR-CLIP (photoactivatable ribonucleoside-enhanced crosslinking and
      immunoprecipitation) facilitates the identification and mapping of protein/RNA
      interactions. So far, it has been limited to select cell-lines as it requires
      efficient 4SU uptake. To increase transcriptome complexity and thus identify
      additional RNA-protein interaction sites we fused HEK 293 T-Rex cells (HEK293-Y)
      that express the RNA binding protein YBX1 with PC12 cells expressing eGFP (PC12
      eGFP). The resulting hybrids enable PAR-CLIP on a neuronally expanded
      transcriptome (Fusion-CLIP) and serve as a proof of principle. The fusion cells
      express both parental marker genes YBX1 and eGFP and the expanded transcriptome
      contains human and rat transcripts. PAR-CLIP of fused cells versus the parental
      HEK293-Y identified 768 novel RNA targets of YBX1. We were able to trace the
      origin of the majority of the short PAR-CLIP reads as they differentially mapped
      to the human and rat genome. Furthermore, Fusion-CLIP expanded the CAUC RNA
      binding motif of YBX1 to UCUUUNNCAUC. The fusion of HEK293-Y and PC12-eGFP cells
      resulted in cells with a diverse genome expressing human and rat transcripts that
      enabled the identification of novel YBX1 substrates. The technique allows the
      expansion of the HEK 293 transcriptome and makes PAR-CLIP available to fusion
      cells of diverse origin.

PMID- 29028414
TI  - Immunization attitudes and practices among family medicine providers.
AB  - OBJECTIVE: To describe immunization attitudes and practices among family medicine
      providers across New York State. METHODS: In this cross-sectional survey study,
      family medicine providers across New York State completed a questionnaire to
      assess vaccine beliefs and barriers and immunization practices. STATISTICAL
      ANALYSIS: Descriptive statistical methods were used to define provider
      characteristics, knowledge and vaccine practices. RESULTS: Completed
      questionnaires from 226 family medicine providers were included for analysis. As
      a group, 207/218 (95%) of providers who answered the question state they always
      recommend standard pediatric vaccines. Of the 209 providers who answered both
      questions, 47 (22%) state they always recommend standard pediatric vaccines but
      do not always recommend HPV vaccine to eligible 11-12 year-old patients. Only 75%
      of providers strongly disagreed with the statement 'vaccinating adolescents
      against HPV increases the likelihood of unprotected sex'. Even though 178/190
      (94%) and 164/188 (87%) of surveyed family medicine providers reported
      recommending that their pregnant patients receive influenza vaccine and Tdap
      vaccine, respectively, only 134/185 (72%) routinely do so in their office.
      CONCLUSION: Most family medicine providers self-report always recommending
      standard pediatric vaccines, however only a minority are following ACIP
      recommendations. Educational sessions to update family medicine providers on ACIP
      recommendations and address individual provider concerns may improve provider
      vaccine confidence and uptake of vaccines by their patients.

PMID- 29028416
TI  - Differences in Risky Sexual Behavior According to Sexual Orientation in Korean
      Adolescents.
AB  - Adolescents in sexual minority groups are known to be at risk of contracting
      sexually transmitted diseases through risky sexual behavior. However, few studies
      have examined associations between sexual orientation and risky sexual behavior
      and sexually transmitted diseases in Korean adolescents. Therefore, this cross
      sectional study used raw data from the Tenth Korea Youth Risk Behavior Web-Based
      Survey to explore these relationships. Logistic regression analyses were
      performed to examine the associations between risky sexual behavior and sexual
      orientation in adolescents. The participants were 6,884 adolescents who provided
      data regarding demographic characteristics, sexual orientation, and risky sexual
      behavior. The proportions of homosexual and bisexual subjects who used condoms,
      engaged in sexual intercourse after drinking alcohol, and experienced sexually
      transmitted diseases were higher relative to those of heterosexual subjects.
      Associations between homosexuality and bisexuality and sexually transmitted
      diseases and engagement in sexual intercourse after drinking remained after
      multivariate adjustment. Interventions to prevent risky sexual behavior should
      target sexual orientation, to improve sexual health and prevent sexually
      transmitted disease in homosexual and bisexual adolescents.

PMID- 29028415
TI  - CRISPR/Cas9-mediated noncoding RNA editing in human cancers.
AB  - Cancer is characterized by multiple genetic and epigenetic alterations, including
      a higher prevalence of mutations of oncogenes and/or tumor suppressors. Mounting
      evidences have shown that noncoding RNAs (ncRNAs) are involved in the epigenetic
      regulation of cancer genes and their associated pathways. The clustered regularly
      interspaced short palindromic repeats (CRISPR)-associated nuclease 9
      (CRISPR/Cas9) system, a revolutionary genome-editing technology, has shed light
      on ncRNA-based cancer therapy. Here, we briefly introduce the classifications and
      mechanisms of CRISPR/Cas9 system. Importantly, we mainly focused on the
      applications of CRISPR/Cas9 system as a molecular tool for ncRNA (microRNA, long
      noncoding RNA and circular RNA, etc.) editing in human cancers, and the novel
      techniques that are based on CRISPR/Cas9 system. Additionally, the off-target
      effects and the corresponding solutions as well as the challenges toward
      CRISPR/Cas9 were also evaluated and discussed. Long- and short-ncRNAs have been
      employed as targets in precision oncology, and CRISPR/Cas9-mediated ncRNA editing
      may provide an excellent way to cure cancer.

PMID- 29028417
TI  - Opioid Prescription Trends Among Patients With Cancer Referred to Outpatient
      Palliative Care Over a 6-Year Period.
AB  - INTRODUCTION: In the United States, opioid regulations have become increasingly
      stringent in recent years. Increased regulatory scrutiny, in part, is related to
      heightened awareness through literature and a recent media blitz on the opioid
      prescription epidemic. These regulations have the potential to impact
      prescription trends by health care providers. Our objective was to evaluate
      changes in the type and dose of opioid prescriptions among patients who are
      referred by oncologists to an outpatient palliative care clinic. MATERIALS AND
      METHODS: We reviewed the electronic health records of 750 patients who were seen
      as new consultations at MD Anderson Cancer Center's outpatient palliative care
      clinic between January 1 and April 30 each year from 2010 through 2015. Data
      collected included demographics, cancer type and stage, symptom assessment,
      performance status, opioid type, and opioid dose defined as the morphine
      equivalent daily dose (MEDD). RESULTS: Median age was 59 years (interquartile
      range [IQR], 51 to 67), 383 (51%) were female, 529 (70%) were white, and 654
      (87%)of patients had advanced cancer. In 2010, median MEDD before referral was 78
      mg/d (IQR, 30 to 150); however, by 2015, the MEDD had progressively decreased to
      40 mg/d (IQR, 19 to 80; P = .001). Hydrocodone was the most common opioid
      prescribed between 2010 and 2015; however, after its reclassification as a
      schedule II opioid in October 2014, the use of tramadol, a schedule IV opioid,
      increased ( P < .001). CONCLUSION: During the past several years, the MEDD
      prescribed by referring oncologists has decreased. After hydrocodone
      reclassification, the use of tramadol with less stringent prescription limits has
      increased.

PMID- 29028419
TI  - An innovative educational clinical experience promoting geriatric exercise.
AB  - Formal educational training in physical activity promotion is relatively sparse
      throughout the medical education system. The authors describe an innovative
      clinical experience in physical activity directed at medical clinicians on a
      geriatrics rotation. The experience consists of a single 2 1/2 hour session, in
      which learners are partnered with geriatric patients engaged in a formal
      supervised exercise program. The learners are guided through an evidence-based
      exercise regimen tailored to functional status. This experience provides learners
      with an opportunity to interact with geriatric patients outside the hospital
      environment to counterbalance the typical geriatric rotation in which geriatric
      patients are often seen in clinics or hospitals. In this experience, learners are
      exposed to fit and engaged geriatric patients successfully living in the
      community despite chronic or disabling conditions. A survey of 105 learners
      highlighted positive responses to the experience, with 96% of survey respondents
      indicating that the experience increased their confidence in their ability to
      serve as advocates for physical activity for older adults, and 89.5% of
      responders to a follow-up survey indicating that the experience changed their
      perception of geriatric patients. Modifications to the experience, implemented at
      partnering facilities are described. The positive feedback from this experience
      warrants consideration for implementation in other settings.

PMID- 29028418
TI  - Cancer Center Clinic and Research Team Perceptions of Identity and Interactions.
AB  - PURPOSE: Conduct of cancer clinical trials requires coordination and cooperation
      among research and clinic teams. Diffusion of and confusion about responsibility
      may occur if team members' perceptions of roles and objectives do not align.
      These factors are critical to the success of cancer centers but are poorly
      studied. METHODS: We developed a survey adapting components of the Adapted Team
      Climate Inventory, Measure of Team Identification, and Measure of In-Group Bias.
      Surveys were administered to research and clinic staff at a National Cancer
      Institute-designated comprehensive cancer center. Data were analyzed using
      descriptive statistics, t tests, and analyses of variance. RESULTS: Responses
      were received from 105 staff (clinic, n = 55; research, n = 50; 61% response
      rate). Compared with clinic staff, research staff identified more strongly with
      their own group ( P < .01) but less strongly with the overall cancer center ( P =
      .02). Both clinic staff and research staff viewed their own group's goals as
      clearer than those of the other group ( P < .01) and felt that members of their
      groups interacted and shared information within ( P < .01) and across ( P < .01)
      groups more than the other group did. Research staff perceived daily outcomes as
      more important than did clinic staff ( P = .05), specifically research-related
      outcomes ( P = .07). CONCLUSION: Although there are many similarities between
      clinic and research teams, we also identified key differences, including
      perceptions of goal clarity and sharing, understanding and alignment with cancer
      center goals, and importance of outcomes. Future studies should examine how
      variation in perceptions and group dynamics between clinic and research teams may
      impact function and processes of cancer care.

PMID- 29028420
TI  - The Effect of Telemedicine on Resource Utilization and Hospital Disposition in
      Critically Ill Pediatric Transport Patients.
AB  - PURPOSE: Pediatric transport teams rely on communication to report patient data
      to medical command officers, who create care plans and determine disposition.
      Common destinations are the emergency department (ED), pediatric intensive care
      unit (PICU), or regular inpatient care area (RIPCA). Telephone report does not
      result in complete understanding of the patient's condition. Further workup in
      the ED is often required. Telemedicine allows the patient to be directly seen;
      parents to be interviewed; and laboratory studies, radiographs, and vital signs
      to be reviewed. We hypothesized that telemedicine would improve understanding of
      the patient and result in more accurate disposition. DESIGN: Patients within our
      hospital from 2012 to 2013 were compared with patients transported using our
      telemedicine program from April 2014 to April 2015. RESULTS: From 2012 to 2013, a
      total of 4,662 transports were performed. Of these, 4,067 were inbound
      transports, 2,302 of these patients were sent to ED (56.6%), 1,062 were sent to
      RIPCA (26%), and 431 were sent to PICU (10.6%). Over a year-long period of
      telemedicine implementation, 212 patients used telemedicine and were analyzed. ED
      utilization decreased to 27% (p < 0.0001), PICU increased to 34.4% (p < 0.0001),
      and RIPCA rates remained the same at 28% (p = 0.203). Of ED dispositions, 58.6%
      were admitted to RIPCA for further care, 13.7% to PICU for escalation of care,
      and 24.1% were discharged. Of RIPCA dispositions, 10% had rapid responses; 0 had
      code blues. Of PICU dispositions, 90.4% had care escalation; 9.6% were observed
      in the PICU without escalation. CONCLUSION: Telemedicine use in transported
      pediatric patients can positively alter disposition patterns.

PMID- 29028421
TI  - Medical student reflections on geriatrics: Moral distress, empathy, ethics and
      end of life.
AB  - Medical students' early clinical encounters may influence their perceptions of
      geriatrics. This study examines reflective essays written by 3rd-year medical
      students on required clinical rotations. Using content analysis, the authors
      analyzed the essays' thematic content. The authors then used chi-squared analysis
      to compare themes with geriatric patients (age 60+) to themes with other age
      groups. One hundred twenty out of 802 essays described a geriatric patient. The
      most common geriatric themes were (1) death and dying, (2) decision making, (3)
      meaningful physician-patient interactions, (4) quality of care, and (5)
      professional development. Geriatric essays were more likely to discuss
      death/dying and risk-benefit themes and less likely to discuss abuse. Geriatric
      essays were more likely to describe students' moral distress. Geriatric essays
      with moral distress were more likely to include empathy themes compared to
      geriatric essays without moral distress. Geriatric patients may pose unique
      ethical challenges for early clinical students.

PMID- 29028422
TI  - Enterococcus faecalis Endophthalmitis in Children - A 21 Year Study.
AB  - PURPOSE: To report Enterococcus faecalis endophthalmitis (EFE) in children and
      its comparison with adults. METHODS: Retrospective study of 19 children up to 18
      years age, undergoing vitrectomy for EFE at a referral eye center from January
      1995 to December 2015. The results were compared to 18 adults with EFE. RESULTS:
      The mean age was 7.4 +/- 3.06 years. Post-traumatic EFE was seen in 17 (89.4%)
      children (p < 0.05) versus postoperative EFE seen in 12 (66%) adults. Broomstick
      9 (52.9%) and hypodermic needle injury 6 (35.2%) were common associations.
      "Optimum functional outcome" was achieved in 12 (63.1%) eyes of children and 5
      (27.7%) eyes of adults (p = 0.03). Sealed and Zone II wounds, lens, and needle
      injuries had good outcome whereas intervention after 3 days and retinal
      detachment had poor outcomes (p < 0.05). The was no correlation with the Ocular
      Trauma Score. CONCLUSION: EFE in children is rare; seen with broom stick and
      needle injuries, if managed early recovers optimum vision.

PMID- 29028423
TI  - 2016 Updates to the WHO Brain Tumor Classification System: What the Radiologist
      Needs to Know.
AB  - Radiologists play a key role in brain tumor diagnosis and management and must
      stay abreast of developments in the field to advance patient care and communicate
      with other health care providers. In 2016, the World Health Organization (WHO)
      released an update to its brain tumor classification system that included
      numerous significant changes. Several previously recognized brain tumor
      diagnoses, such as oligoastrocytoma, primitive neuroectodermal tumor, and
      gliomatosis cerebri, were redefined or eliminated altogether. Conversely,
      multiple new entities were recognized, including diffuse leptomeningeal
      glioneuronal tumor and multinodular and vacuolating tumor of the cerebrum. The
      glioma category has been significantly reorganized, with several infiltrating
      gliomas in children and adults now defined by genetic features for the first
      time. These changes were driven by increased understanding of important genetic
      factors that directly impact tumorigenesis and influence patient care. The
      increased emphasis on genetic factors in brain tumor diagnosis has important
      implications for radiology, as we now have tools that allow us to evaluate some
      of these alterations directly, such as the identification of 2-hydroxyglutarate
      within infiltrating gliomas harboring mutations in the genes for the isocitrate
      dehydrogenases. For other tumors, such as medulloblastoma, imaging can
      demonstrate characteristic patterns that correlate with particular disease
      subtypes. The purpose of this article is to review the changes to the WHO brain
      tumor classification system that are most pertinent to radiologists. (c)RSNA,
      2017.

PMID- 29028424
TI  - Unique Tailoring of Th17 at the Gingival Oral Mucosal Barrier.
AB  - Our recent work highlights unique requirements for the induction of Th17 cells at
      the oral/gingival mucosal barrier. Unlike other barrier sites, such as the skin
      and gastrointestinal tract, we found that Th17 cells can develop at the gingiva
      independently of commensal microbiota colonization. Instead, we identified that
      damage, which occurs physiologically due to mastication, promotes induction of
      Th17 cells and tones homeostatic immunity at the gingiva.

PMID- 29028425
TI  - Movement Variability Increases With Shoulder Pain When Compensatory Strategies of
      the Upper Body Are Constrained.
AB  - This cross-sectional study analyzed the influence of chronic shoulder pain (CSP)
      on movement variability/kinematics during humeral elevation, with the trunk and
      elbow motions constrained to avoid compensatory strategies. For this purpose, 37
      volunteers with CSP as the injured group (IG) and 58 participants with
      asymptomatic shoulders as the control group (CG) participated in the study.
      Maximum humeral elevation (Emax), maximum angular velocity (Velmax), variability
      of the maximum angle (CVEmax), functional variability (Func_var), and approximate
      entropy (ApEn) were calculated from the kinematic data. Patients' pain was
      measured on the visual analogue scale (VAS). Compared with the CG, the IG
      presented lower Emax and Velmax and higher variability (i.e., CVEmax, Func_var,
      and ApEn). Moderate correlations were achieved for the VAS score and the
      kinematic variables Emax, Velmax and variability of curve analysis, Func_varm,
      and ApEn. No significant correlation was found for CVEmax. In conclusion, CSP
      results in a decrease of angle and velocity and an increased shoulder movement
      variability when the neuromuscular system cannot use compensatory strategies to
      avoid painful positions.

PMID- 29028426
TI  - A Single-Bead-Based, Fully Integrated Microfluidic System for High-Throughput
      CD4+T Lymphocyte Enumeration.
AB  - A single-bead-based, fully integrated microfluidic system has been developed for
      high-throughput CD4+T lymphocyte enumeration at point-of-care testing. Instead of
      directly counting CD4+T lymphocytes, CD4+T lymphocyte enumeration is achieved by
      quantitatively detecting CD4 antigen from the lysed blood sample with a
      functionalized polycarbonate single bead based on chemiluminescence. To implement
      the sandwiched chemiluminescence immunoassay with reduced nonspecific binding, a
      streamlined microfluidic chip with multiple reaction chambers is developed to
      allow each reaction step to be completed in an independent chamber where reagent
      is pre-stored. With simple magnetic control, the single bead with an embedded
      ferrous core can be consecutively transported between each of two adjacent
      chambers for different reactions. Meanwhile, enhanced mixing can be achieved by
      moving the single bead back and forth inside one chamber with magnetic actuation.
      High-throughput detection can be performed when a linear actuation stage is
      adopted to introduce synchronous magnetic control to multiple single beads in
      parallel microfluidic chips. A sensitive charge-coupled device (CCD) camera is
      adopted for high-throughput chemiluminescence detection from multiple single
      beads. Experimental results show that with the fully integrated microfluidic
      system, easy-to-operate, accurate, low-cost, immediate, and high-throughput CD4+T
      lymphocyte enumeration can be successfully achieved at resource-poor settings.

PMID- 29028427
TI  - Air quality measurements-From rubber bands to tapping the rainbow.

PMID- 29028428
TI  - Introduction to a special grouping of papers from the 2016 Air Quality
      Measurement Methods and Technology Conference.

PMID- 29028430
TI  - Curcumin Prevents Osteoarthritis by Inhibiting the Activation of Inflammasome
      NLRP3.
AB  - Curcumin has shown protective potential on osteoarthritis. However, its effect on
      treatment of osteoarthritis remains elusive so far. This study aimed to determine
      whether curcumin could ameliorate osteoarthritis in vivo and the underline
      mechanisms. The mice subjected to destabilization of the medial meniscus (DMM)
      surgery were administered curcumin. Cartilage integrity was evaluated by
      immunohistological staining. Expression levels of inflammatory cytokines from
      mice arthrodial cartilage were detected. THP-1 cells were primed by
      lipopolysaccharide (LPS)/ATP to induce inflammation, followed by the addition of
      curcumin. The expression of proinflammatory cytokines was also detected.
      Moreover, the expression of pro-caspase-1, cleaved caspase-1, and NLRP3
      inflammasome was examined. Administration of curcumin significantly reduced
      osteoarthritis disease progression in DMM model of osteoarthritis. Curcumin
      suppressed mRNA expression of proinflammatory mediators in arthrodial cartilage
      of mice subjected to surgery. In LPS- and ATP-induced THP-1 macrophage cells,
      curcumin significantly suppressed the expression of interleukin 1 beta (IL-1beta)
      and tumor necrosis factor alpha (TNF-alpha) at both RNA and protein levels.
      Compared to vehicle-treated controls, curcumin also showed remarkably increased
      pro-caspase-1 and decreased cleaved caspase-1. This study provides the first
      evidence that curcumin exerts protection on osteoarthritis by inhibition to the
      release of inflammasome NLRP3, leading to the downregulation of inflammatory
      cytokines.

PMID- 29028431
TI  - Interferon Tau Regulates Cytokine Production and Cellular Function in Human
      Trophoblast Cell Line.
AB  - Type I interferons (IFN), including IFN-beta (IFNB), activate multiple STAT
      signaling to drive various biological responses. Another type I IFN, IFN-tau
      (IFNT), secreted by ruminant embryonic trophoblast cells, has multiple functions
      with low cytotoxicity. Here, we examined the effects of IFNT on human trophoblast
      cell functions. First, we performed next-generation sequencing and demonstrated
      that IFNT-dependent changes in the human Sw.71 trophoblast cell line are partly
      mediated by proinflammatory as well as IFN signaling. Next, we validated
      candidate genes, and data confirmed that IFNT stimulated interleukin-6 (IL-6) and
      IL-8 mRNA expression and secretion. However, human IFNB did not affect IL-6 and
      IL-8 mRNA expression and secretion. IFNT-induced cytokine secretion was dependent
      on STAT3 signaling, but not STAT1 signaling. In addition, treatment with IFNT, IL
      6, or IL-8 increased cell proliferation, and IFNT also stimulated cell migration
      in human trophoblast cells. Although IFNT did not affect superoxide dismutase
      (SOD) 1 mRNA expression, it clearly increased mitochondrial SOD2 mRNA expression,
      resulting in the acceleration of SOD activity. We demonstrated that in addition
      to IFN signaling, IFNT also regulated inflammation-related signaling as well as
      cell proliferation, migration, and redox signaling in human trophoblast cells.

PMID- 29028432
TI  - Coadministration of Recombinant Adenovirus Expressing GM-CSF with Inactivated
      H5N1 Avian Influenza Vaccine Increased the Immune Responses and Protective
      Efficacy Against a Wild Bird Source of H5N1 Challenge.
AB  - Wild birds play a key role in the spread of avian influenza virus (AIV). There is
      a continual urgent requirement for AIV vaccines to address the ongoing genetic
      changes of AIV. In the current study, we trialed a novel AIV vaccine against the
      wild bird source of H5N1 type AIV with recombinant adenovirus expressing
      granulocyte monocyte colony-stimulating factor (GM-CSF) as an adjuvant. A total
      of 150-day-old commercial chicks, with AIV-maternal-derived antibody, were
      divided into 6 groups. The primary vaccination was performed at day 14 followed
      by a subsequent boosting and intramuscular challenge on day 28 and 42,
      respectively. Recombinant GM-CSF (rGM-CSF) expressed by adenovirus, named as rAd
      GM-CSF, raised the hemagglutination inhibition (HI) titers (log2) against AIV
      from 7.0 (vaccinate with inactivated vaccine alone) to 8.4 after booster
      immunization. Moreover, the rGM-CSF addition markedly increased the expression of
      interferon-gamma, interleukin-4, and major histocompatibility complex-II in the
      lungs, compared with those immunized with inactivated vaccine alone on day 29,
      that is, 18 h post booster immunization. Following challenge, chicks inoculated
      with the inactivated AIV vaccine and rAd-GM-CSF together exhibited mild clinical
      signs and 62% survivals compared to 33% in the group immunized with inactivated
      AIV vaccine alone. Higher level of HI titers, immune related molecule
      expressions, and protection ratio demonstrates a good potential of rGM-CSF in
      improving humoral and cell mediated immune responses of inactivated AIV vaccines.

PMID- 29028435
TI  - Evaluation of Agricultural Interventions on Human and Poultry-Related Salmonella
      Enteritidis in British Columbia.
AB  - A collaborative investigation between public health and animal health led to
      numerous interventions along the food chain in response to an outbreak of human
      salmonellosis and increased incidence of Salmonella Enteritidis (SE) among
      poultry. Incidence of both human and chicken SE decreased substantially in 2012
      and 2013 following these interventions. We used time series analysis to assess
      the impact of three interventions: vaccination of broiler breeder flocks,
      separation in the hatchery of breeder eggs, and an industry order to stop farm
      gate sales of ungraded broiler hatching eggs. Results show a Granger causal
      association between human SE incidence and SE incidence in chickens 8 months
      earlier. Among the interventions, separation of breeder flocks showed a
      consistent and statistically significant association with declining SE incidence
      in chickens. Our results did not show consistent declines in chicken SE following
      breeder flock vaccination (live or inactivated vaccine). None of the
      interventions had statistically significant impacts on human SE incidence. Our
      results are consistent with a positive effect of certain interventions and also
      reveal where additional data are needed for a more comprehensive evaluation.
      Multiple interventions throughout the food chain are best practices when dealing
      with enteric pathogens; collecting data on the timing and intensity of these
      interventions allow proper evaluation of their independent and combined effects.
      Finally, we identify considerations for others interested in undertaking similar
      evaluations. Ongoing collaborative work between public health and animal health
      is required to refine strategies for SE control in British Columbia.

PMID- 29028434
TI  - Gender Differences in Hostility and Aggression Among Military Healthcare
      Personnel After Deployment.

PMID- 29028436
TI  - Pain Management After Hip Arthroscopy: Systematic Review of Randomized Controlled
      Trials and Cohort Studies.
AB  - BACKGROUND:: Hip arthroscopy is often associated with significant postoperative
      pain and opioid-associated side effects. Effective pain management after hip
      arthroscopy improves patient recovery and satisfaction and decreases opioid
      related complications. PURPOSE:: To collect, examine, and provide a comprehensive
      review of the available evidence from randomized controlled trials and
      comparative studies on pain control after hip arthroscopy. STUDY DESIGN::
      Systematic review. METHODS:: Using the Preferred Reporting Items for Systematic
      Reviews and Meta-analyses guidelines, a systematic review of the literature for
      postoperative pain control after hip arthroscopy was performed using electronic
      databases. Only comparative clinical studies with level 1 to 3 evidence comparing
      a method of postoperative pain control with other modalities or placebo were
      included in this review. Case series and studies without a comparative cohort
      were excluded. RESULTS:: Several methods of pain management have been described
      for hip arthroscopy. A total of 14 studies met our inclusion criteria: 3 on
      femoral nerve block, 3 on lumbar plexus block, 3 on fascia iliaca block, 4 on
      intra-articular injections, 2 on soft tissue surrounding surgical site injection,
      and 2 on celecoxib (4 studies compared 2 or more methods of analgesia). The
      heterogeneity of the studies did not allow for pooling of data. Single-injection
      femoral nerve blocks and lumbar plexus blocks provided improved analgesia, but
      increased fall rates were observed. Fascia iliaca blocks do not provide adequate
      pain relief when compared with surgical site infiltration with local anesthetic
      and are associated with increased risk of cutaneous nerve deficits. Patients
      receiving lumbar plexus block experienced significantly decreased pain compared
      with fascia iliaca block. Portal site and periacetabular injections provide
      superior analgesia compared with intra-articular injections alone. Preoperative
      oral celecoxib, compared with placebo, resulted in earlier time to discharge and
      provided significant pain relief up to 24 hours. CONCLUSION:: Perioperative nerve
      blocks provide effective pain management after hip arthroscopy but must be used
      with caution to decrease risk of falls. Intra-articular and portal site
      injections with local anesthetics and preoperative celecoxib can decrease opioid
      consumption. There is a lack of high-quality evidence on this topic, and further
      research is needed to determine the best approach to manage postoperative pain
      and optimize patient satisfaction.

PMID- 29028437
TI  - Stimulants Do Not Increase the Risk of Seizure-Related Hospitalizations in
      Children with Epilepsy.
AB  - OBJECTIVE: To evaluate the safety of stimulants in children with epilepsy.
      METHODS: In a retrospective cohort study based on Medicaid Analytic eXtract
      billing records from 26 U.S. states from 1999 to 2010, we identified incident
      stimulant use among children with epilepsy through outpatient encounter claims
      and pharmacy claims. We established a control group of nonusers and used
      frequency matching to generate index dates. We followed both cohorts for 12
      months and calculated hazard ratios [HRs] of current and former use of stimulants
      versus no use on the outcome of seizure-related hospitalization using
      multivariate Cox proportional hazard models. RESULTS: We identified 18,166
      stimulant users and 54,197 nonusers in children with epilepsy. The incidence of
      seizure-related hospitalization in current stimulant users, former users, and
      nonusers was 3.6, 3.5, and 4.3 per 100 patient-years. After adjustment for
      confounders, we found current and former use of stimulants did not increase
      seizure-related hospitalizations (HR 0.95, 95% confidence interval [CI]: 0.83,
      1.09 and HR 0.99, 95% CI: 0.85, 1.15). Children with cerebral palsy, congenital
      nervous system anomalies, or intellectual disability did not have significantly
      higher HRs than those without the already mentioned comorbidities. CONCLUSION:
      This study has not identified any overall increase in the rate of seizure-related
      hospitalizations with the use of stimulants in children with epilepsy.

PMID- 29028438
TI  - Laser Sintering Technology and Balling Phenomenon.
AB  - OBJECTIVE: The aim of this review was to evaluate the balling phenomenon which
      occurs typically in Selective Laser Sintering (SLS). BACKGROUND DATA: The balling
      phenomenon is a typical SLS defect, and observed in laser sintered powder,
      significantly reduces the quality of SLS, and hinders the further development of
      SLS Technology. METHODS: Electronic database searches were performed using Google
      Scholar. The keywords "laser sintering, selective laser sintering, direct metal
      laser melting, and balling phenomenon" were searched in title/abstract of
      publications, limited to December 31, 2016. The inclusion criteria were SLS,
      balling phenomenon, some alloys (such as Cr-Co, iron, stainless steel, and Cu
      based alloys) mechanical properties, microstructure and bond strength between
      metal-ceramic crown, laboratory studies, full text, and in English language.
      RESULTS: A total of 100 articles were found the initial search and yielded a
      total of 50 studies, 30 of which did not fulfill the inclusion criteria and were
      therefore excluded. In addition, 20 studies were found by screening the reference
      list of all included publications. Finally, 40 studies were selected for this
      review. CONCLUSIONS: The method in question is regulated by powder material
      characteristics and the conditions of laser processing. The procedure of
      formation, affecting factors, and the mechanism of the balling effect are very
      complex.

PMID- 29028439
TI  - A Dyadic Approach to Understanding the Link Between Sexual Functioning and Sexual
      Satisfaction in Heterosexual Couples.
AB  - Researchers have demonstrated that several dimensions of sexual functioning
      (e.g., sexual desire, arousal, orgasm) are associated with the sexual
      satisfaction of individuals in a committed mixed-sex (male-female) relationship.
      We extended this research by comparing a dyadic model that included both own
      (i.e., actor effect) and partner (i.e., partner effect) domains of sexual
      functioning to an individual model that included only actor effects. Participants
      were 124 mixed-sex couples who completed online measures of sexual functioning
      and sexual satisfaction. Data analysis using the actor-partner interdependence
      model (APIM) and structural equation modeling (SEM) indicated that the dyadic
      model had a better fit than the individual model. Women's sexual desire and
      orgasm and men's erectile functioning were significant positive predictors of
      both own and partner's sexual satisfaction. These results are discussed in terms
      of the importance of taking a dyadic approach to research and clinical work
      related to sexual satisfaction.

PMID- 29028440
TI  - Intracerebroventricular infusion of angiotensin AT2 receptor agonist novokinin
      aggravates some diabetes-mellitus-induced alterations in Wistar rats.
AB  - Cumulative data suggest the significant role of the renin-angiotensin system in
      the development of the pathological consequences of diabetes mellitus (DM). Newly
      synthesized AT2 receptor agonists gained importance as a target for creating new
      antihypertensives. The aim of the present work was to study the effects of
      peptide AT2 agonist novokinin, infused intracerebroventricularly, on the
      consequences of the streptozotocin-induced type 1 DM (T1DM) in Wistar rats. Food
      and water consumption, body mass, urine excretion (metabolic cages), motor
      activity (open-field test), anxiety (elevated plus maze), nociception (paw
      pressure analgesimeter test), spatial memory (T-maze alternation test), and
      plasma levels of glucose and corticosterone (ELISA) were assessed 2 weeks after
      the T1DM induction. Novokinin increased water and food consumption, as well as
      urine output, and reduced mass gain in the control rats. Diabetic rats
      demonstrated hyperalgesia, increased level of plasma corticosterone, decreased
      motor and exploratory activity, and impaired spatial memory. Novokinin infusion
      increased water intake, diuresis, and mortality rate, decreased food intake,
      exacerbated diabetes-induced hyperalgesia, and provoked anxiety-like behavior but
      improved spatial memory in diabetic rats. These initial data suggest that
      angiotensin AT2 receptors participate in the pathogenesis of T1DM-induced
      complications in the function of the nervous system.

PMID- 29028441
TI  - Physiological and pharmacological inductors of HSP70 enhance the antioxidative
      defense mechanisms of the liver and pancreas in diabetic rats.
AB  - Heat preconditioning (HP) is a powerful adaptive and protective phenomenon and
      the heat stress proteins (HSPs) it produces are an important determinant for the
      development of diabetic complications. Aspirin has been reported to modulate heat
      shock response in different organisms through increased induction of HSPs and is
      also known to exert antioxidative and radical scavenging effects in diabetes. We
      estimated the effect of physiological (heat stress: 45 min at 41 +/- 0.5  degrees
      C) and pharmacological (aspirin treatment) induction of HSP70 on several
      parameters of oxidative state in the pancreas and liver of diabetic rats.
      Diabetes increased HSP70 level and decreased poly(ADP) ribose polymerase (PARP),
      glutathione (GSH), and glutathione peroxidase (GPx) activities in the pancreas.
      In the liver, there was reduction of HSP70 level, GSH concentration, and CAT
      activity, while GPx and GR activity were enhanced. HP of diabetic rats caused an
      additional increase of HSP70, GSH, and antioxidant enzymes in both organs. Pre
      treatment of HP-diabetic animals with aspirin led to an additional increase of
      PARP and HSP70. Both HP and aspirin, as physiological and pharmacological
      inductors of HSP70, respectively, enhanced the antioxidative defense mechanisms
      of the liver and pancreas in diabetic rats.

PMID- 29028442
TI  - The Use of Mobile Applications Among Adults with Type 1 and Type 2 Diabetes:
      Results from the Second MILES-Australia (MILES-2) Study.
AB  - BACKGROUND: While the number of diabetes-specific mobile applications (apps)
      continues to grow, there is a lack of knowledge about their actual use. METHODS:
      The second MILES (Management and Impact for Long-term Empowerment and Success)
      Australia study was a national cross-sectional survey of the psychological,
      behavioral, and social aspects of diabetes for adults with type 1 diabetes (T1D)
      and type 2 diabetes (T2D). Associations between diabetes-specific app usage and
      demographic, clinical, and psychosocial variables were examined. RESULTS: Of the
      1589 respondents responding to the diabetes-specific app questions, 795 had T1D
      (mean +/- standard deviation age 43 +/- 14 years; 61% women; diabetes duration 19
      +/- 14 years) and 794 had T2D (age 60 +/- 9 years; 40% women; diabetes duration
      11 +/- 7 years). Among adults with T1D, 24% (n = 188) reported using apps, with
      carbohydrate counting (74%; n = 139) as the most common cited purpose. App usage
      was significantly associated with shorter diabetes duration, more frequent
      glucose monitoring, and lower self-reported HbA1c. Among adults with T2D, 8% (n =
      64) reported using apps, with glucose monitoring (62%; n = 39) as the most common
      purpose. For all respondents, the most commonly reported reason for not using
      apps was a belief that they could not help with diabetes self-management.
      CONCLUSIONS: A minority of adults with T1D and T2D use apps to support their self
      management. App use among adults with T1D is associated with a more recent T1D
      diagnosis, more frequent glucose monitoring, and lower self-reported HbA1c.
      Future efforts should focus on this association and determine the mechanisms by
      which app use is related to better clinical outcomes.

PMID- 29028443
TI  - Diagnosing at a Distance: Is the Goldwater Rule Still Relevant Today?

PMID- 29028445
TI  - Return to Sport-Specific Performance After Primary Anterior Cruciate Ligament
      Reconstruction: A Systematic Review.
AB  - BACKGROUND:: Physicians counseling athletes on the prognosis of sport-specific
      performance outcomes after anterior cruciate ligament reconstruction (ACLR)
      depend on the published literature. However, critical appraisal of the validity
      and biases in these studies is required to understand how ACLR affects an
      athlete's ability to return to sport, the athlete's sport-specific performance,
      and his or her ability to achieve preinjury levels of performance. PURPOSE:: This
      review identifies the published prognostic studies evaluating sport-specific
      performance outcomes after ACLR. A risk of bias assessment and summaries of
      return to sport and career longevity results are provided for each included
      study. STUDY DESIGN:: Systematic review. METHODS:: Electronic databases (Ovid
      MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central
      Register of Controlled Trials, and PUBMED) were searched via a defined search
      strategy with no limits, to identify relevant studies for inclusion in the
      review. A priori defined eligibility criteria included studies measuring sport
      specific performance within an athlete's sport, before and after primary ACLR.
      Reference lists of eligible studies were hand-searched for additional relevant
      studies. Data extraction was performed by use of a standardized spreadsheet. Each
      included study was assessed by use of 6 bias domains of the Quality in Prognosis
      Studies tool to critically appraise study participation, study attrition,
      prognostic factors, outcome measurement, confounders, and statistical analysis
      and reporting. Two authors independently performed each stage of the review and
      reached consensus through discussion. RESULTS:: Fifteen pertinent prognostic
      studies evaluated sport-specific performance outcomes and/or return to play after
      ACLR for athletes participating in competitive soccer, football, ice hockey,
      basketball, Alpine ski, X-Games ski and snowboarding, and baseball. Twelve of
      these studies were considered to have a high level of bias. CONCLUSION:: This
      review demonstrated that most high-performance or professional athletes returned
      to their preinjury level of sport after ACLR. The bulk of evidence suggests there
      was a measurable decrease in performance statistics, although this is highly
      sport-specific. A paucity of literature is available that addresses sport
      specific performance in athletes after ACLR. This review has determined that the
      available literature is highly biased and must be read with caution. CLINICAL
      RELEVANCE:: By better understanding the validity and biases in the published
      literature, physicians can provide more informed prognoses about return to sport
      specific performance after ACLR while considering risk factors relevant to their
      patients. REGISTRATION:: CRD42016046709 (International Prospective Register of
      Systematic Reviews, https://www.crd.york.ac.uk/prospero/ ).

PMID- 29028444
TI  - Development and In-House Validation of a Real-Time Polymerase Chain Reaction for
      the Detection of Listeria monocytogenes in Meat.
AB  - Listeriosis is a foodborne disease caused by Listeria monocytogenes. The aims of
      this work were to develop and validate an in-house real-time polymerase chain
      reaction (RT-PCR) for the detection of L. monocytogenes, and to determine its
      prevalence in raw ground beef samples from 53 butcheries that also sell ready-to
      eat foods. One set of primers and one hydrolysis probe were designed for hly gene
      detection and then challenged with pure strains. The detection was successful for
      all L. monocytogenes strains analyzed and negative for all non-L. monocytogenes
      strains (detection limit, 10 colony forming unit [CFU]/mL). Inclusivity,
      exclusivity, and analytical accuracy were 100%. L. monocytogenes was detected in
      41.5% of raw ground beef samples from the 53 butcheries analyzed. This RT-PCR may
      be a valuable method for rapid detection of L. monocytogenes in meat.

PMID- 29028446
TI  - Out of "Objectification Limelight"? The Contribution of Body Appreciation to
      Sexual Adjustment in Midlife Women.
AB  - According to objectification theory, women become culturally desexualized during
      midlife and have the opportunity to let go of their propensity to self-objectify.
      In young women, self-objectification is negatively related to sexual adjustment.
      Yet little is known about what could ameliorate this relationship or whether it
      continues after midlife. Body appreciation (i.e., acceptance and positive regard
      for the body) has been substantiated as a contributor to improved sexual
      adjustment in young and older women alike. Hence, this study was designed to
      examine whether it helps mitigate the deleterious effect of self-objectification
      on sexual function, satisfaction, and distress in women over the age of 50 (n =
      193). Path analyses revealed that self-surveillance is related to body shame and
      appearance anxiety, the latter of which was related to body self-consciousness
      during sex. In turn, body self-consciousness during sex mediated the relationship
      between body shame, appearance anxiety, and all three indicators of sexual
      adjustment. Furthermore, high body appreciation attenuated the negative
      associations between self-objectification constructs, body self-consciousness
      during sex, and sexual satisfaction and distress. Overall, this study supports
      the use of objectification theory in midlife and older women. Sex therapy
      interventions that incorporate mindfulness and body appreciation principles are
      discussed.

PMID- 29028447
TI  - Complications of Home Enteral Nutrition: Mechanical Complications and Access
      Issues in the Home Setting [Formula: see text].
AB  - Home enteral nutrition (HEN) is an essential component in the care of patients
      with an array of underlying etiologies resulting in the inability to meet caloric
      needs through volitional intake alone. Although some would include oral nutrition
      supplementation as HEN, for the purposes of this review, the term is limited to a
      patient's requiring an enteral access device for the delivery of exogenous
      nutrients. Complications related to such devices remain a difficult problem in
      the hospital setting, and these issues are often amplified when encountered in
      the home setting. Focused multidisciplinary teams and close follow-up are
      essential in optimizing outcomes for patients receiving HEN, but all healthcare
      providers should have foundational knowledge regarding commonly encountered
      complications of HEN access and the initial management of these issues.

PMID- 29028448
TI  - Characterization of the Stool Microbiome in Hispanic Preschool Children by Weight
      Status and Time.
AB  - BACKGROUND: Variations in gut microbiota composition and diversity have been
      associated with childhood adiposity, although most studies describing this have
      been cross-sectional in nature. Our objective was to evaluate associations
      between body weight and the gut microbiota over time in obese preschool-age
      children. METHODS: Obese, preschool-age, Hispanic children provided stool samples
      at baseline and following a 6-month behavioral intervention. Normal-weight (NW)
      children also provided stool samples. Stool microbial community composition was
      characterized using 16S rRNA gene sequencing. Estimates of within-sample
      diversity were calculated on operational taxonomic unit (OTU) count data, and the
      Firmicutes:Bacteroidetes (F:B) ratio was determined on per-sample basis.
      Estimates of between-sample diversity were generated using the weighted Unifrac
      metric, differential abundances were evaluated using Wilcoxon rank-sum tests, and
      associations of microbiome features with clinical data were quantified using
      Spearman rank correlations. RESULTS: For the 30 obese children sampled
      preintervention and postintervention, a decrease in body mass index (BMI) z-score
      from 2.55 to 2.34 (p = 0.004, paired t-test) was observed. Bacteroides
      massiliensis was significantly enriched in obese children, while B. plebius was
      significantly enriched in NW controls. We identified significant correlations
      between multiple Bacteroides-like OTUs and BMI z-score, but neither F:B ratios
      nor OTU-level abundances were altered in conjunction with weight change in the
      obese children. Rather, highly individualized OTU-level responses were observed.
      CONCLUSIONS: Although differences exist between the gut microbiota of obese and
      NW children, we detected highly individualized responses of the gut microbiota of
      obese children over time and following weight loss.

PMID- 29028449
TI  - Geometric Characteristics of the Knee Are Associated With a Noncontact ACL Injury
      to the Contralateral Knee After Unilateral ACL Injury in Young Female Athletes.
AB  - BACKGROUND: Contralateral anterior cruciate ligament (CACL) injury after recovery
      from a first-time ACL rupture occurs at a high rate in young females; however,
      little is known about the risk factors associated with bilateral ACL trauma.
      HYPOTHESIS: The geometric characteristics of the contralateral knee at the time
      of the initial ACL injury are associated with risk of suffering a CACL injury in
      these female athletes. STUDY DESIGN: Case-control study; Level of evidence, 3.
      METHODS: Sixty-two female athletes who suffered their first noncontact ACL injury
      while participating in sports at the high school or college level were
      identified, and geometry of the femoral notch, ACL, tibial spines, tibial
      subchondral bone, articular cartilage surfaces, and menisci of the contralateral,
      uninjured, knee was characterized in 3 dimensions. We were unable to contact 7
      subjects and followed the remaining 55 until either a CACL injury or an ACL graft
      injury occurred or, if they were not injured, until the date of last contact
      (mean, 34 months after their first ACL injury). Cox regression was used to
      identify risk factors for CACL injury. RESULTS: Ten (18.2%) females suffered a
      CACL injury. Decreases of 1 SD in femoral intercondylar notch width (measured at
      its outlet and anterior attachment of the ACL) were associated with increases in
      the risk of suffering a CACL injury (hazard ratio = 1.88 and 2.05, respectively).
      Likewise, 1 SD decreases in medial-lateral width of the lateral tibial spine,
      height of the medial tibial spine, and thickness of the articular cartilage
      located at the posterior region of the medial tibial compartment were associated
      with 3.59-, 1.75-, and 2.15-fold increases in the risk of CACL injury,
      respectively. CONCLUSION: After ACL injury, subsequent injury to the CACL is
      influenced by geometry of the structures that surround the ACL (the femoral notch
      and tibial spines). This information can be used to identify individuals at
      increased risk for CACL trauma, who might benefit from targeted risk-reduction
      interventions.

PMID- 29028451
TI  - Questioning the Goldwater Rule: Commentary on Lilienfeld, Miller, and Lynam.

PMID- 29028450
TI  - Comparing two approaches of miR-34a target identification, biotinylated-miRNA
      pulldown vs miRNA overexpression.
AB  - microRNAs (miRNAs) are critical regulators of gene expression. For elucidating
      functional roles of miRNAs, it is critical to identify their direct targets.
      There are debates about whether pulldown of biotinylated miRNA mimics can be used
      to identify miRNA targets or not. Here we show that biotin-labelled miR-34a can
      be loaded to AGO2, and AGO2 immunoprecipitation can pulldown biotinylated miR-34a
      (Bio-miR pulldown). RNA-sequencing (RNA-seq) of the Bio-miR pulldown RNAs
      efficiently identified miR-34a mRNA targets, which could be verified with
      luciferase assays. In contrast to the approach of Bio-miR pulldown, RNA-seq of
      miR-34a overexpression samples had limited value in identifying direct targets of
      miR-34a. It seems that pulldown of 3'-Biotin-tagged miRNA can identify bona fide
      microRNA targets at least for miR-34a.

PMID- 29028453
TI  - A Qualitative Exploration of Adult Baby/Diaper Lover Behavior From an Online
      Community Sample.
AB  - This study examined qualitative data on 1,795 male, 139 female, and 78
      transgender members of the adult baby/diaper lover (ABDL) online community. Using
      grounded theory, the analyses examined a description of ABDL practices, explored
      evidence of subgroups within the ABDL community, and examined the degree to which
      ABDL behavior involves sexual motivations. Overall, the data suggest there is a
      fair amount of diversity within the ABDL community. Most participants enjoy
      wearing diapers or engaging in age regression (as babies or children), and the
      importance of incontinence may vary. ABDL practices can reflect bondage play for
      some individuals and a way to cope with medical problems for others. Overall,
      there is modest evidence of more than two ABDL subgroups. Although a large number
      of individuals do not see their ABDL practices as sexual in nature, there is a
      clear contingent that describes sexual motivations. For some, sex during ABDL
      activity violates conceptions of baby play. Nonsexual motivations include a
      desire to relax or be carefree as well as a desire to be nurtured. Some diaper
      lovers and adult babies have the same goals but achieve them in different ways.
      ABDL practices may be as diverse as seemingly typical sexual behaviors.

PMID- 29028452
TI  - Atrial Fibrillation in Women: Risks and Management.
AB  - Atrial fibrillation (AF) is one of the most commonly occurring arrhythmias and a
      major modifiable risk factor for stroke, especially in women. While its
      prevalence is similar in both men and women, women unfortunately face a greater
      intrinsic AF-related risk of stroke than men do. This is likely one of the
      reasons that more women than men die from strokes, in addition to experiencing
      more new and recurrent strokes. Therefore, in women especially, it is imperative
      to diagnose and treat AF as early as possible. While its unreliable symptom
      profile and possible intermittent nature can make AF difficult to detect,
      proactive identification of risk factors and improved detection methods can help.
      Additionally, the use of risk stratification schemes for anticoagulant therapy,
      along with the efficacy of nonvitamin K antagonist anticoagulants can enable
      appropriate therapy to prevent stroke occurrence.

PMID- 29028454
TI  - The Longtan Modification: An Effective and Economical Surgical Innovation for
      Parastomal Hernia Post-Intraperitoneal Sigmoidostomy.
AB  - PURPOSE: This study was designed to introduce a new surgical innovation, referred
      to as the "Longtan modification," for cases with parastomal hernia (PSH)
      following intraperitoneal sigmoidostomy, and to assess the safety and feasibility
      of this procedure. METHODS: Between January 2013 and June 2016, a total of 26
      consecutive cases with PSH successfully underwent this procedure. The patient
      demographics, surgical outcomes, stoma-related complications, and the stoma
      function were collected and analyzed. RESULTS: Mean diameter of the hernia ring
      was 7.6 cm, mean operation time was 94.2 minutes, and mean intraoperative blood
      loss was 18.0 mL. The mean period of postoperative hospitalization was 4.4 days
      while the mean hospitalization cost was only $3,750 USD. There were no severe
      complications such as postoperative hemorrhage, ischemic necrosis, peritoneal
      infection, or intestinal obstruction, although one case suffered from
      postoperative infection at the site of incision. None of the cases had a
      recurrence of PSH during the follow-up period. In addition, the stoma functioned
      efficiently and appropriately following the Longtan modification. CONCLUSION:
      Overall, the Longtan modification appears to be an effective and economical
      surgical innovation for cases with PSH following intraperitoneal sigmoidostomy.

PMID- 29028456
TI  - Visual Attention Patterns Differ in Gynephilic and Androphilic Men and Women
      Depending on Age and Gender of Targets.
AB  - Visual attention patterns measured with eye-tracking techniques provide indirect
      clues about sexual response. This study aimed to test the category specificity of
      sexual responses to stimuli varying in gender and age by evaluating both early
      and late attention of gynephilic and androphilic men and women. We simultaneously
      presented sexually preferred and nonpreferred stimuli and measured time to first
      fixation and total duration of fixation on four areas of interest: entire body,
      then face, chest, and pelvis. Androphilic women's early attention patterns were
      nonspecific, whereas gynephilic women and both groups of men showed a category
      specific pattern for the entire body. In contrast, all groups showed gender
      specific patterns of late attention for all areas of interest. We also found
      support for age specificity of early and late visual attention in all four
      groups, with greater attention to adult than child stimuli. This study supports
      the usefulness of a competing stimulus eye-tracking paradigm as a method to
      examine gender specificity in gynephilic women and androphilic and gynephilic
      men, and as a measure of age specificity in gynephilic and androphilic men and
      women.

PMID- 29028455
TI  - Health Indicators for Older Sexual Minorities: National Health Interview Survey,
      2013-2014.
AB  - PURPOSE: Advances in lesbian, gay, and bisexual (sexual minority [SM]) acceptance
      and equality have been made in the past decade. However, certain SM subgroups
      continue to be disadvantaged due to lack of data and, thus, lack of knowledge
      about these populations. Data for older sexual minorities are especially lacking
      and will be increasingly important as more sexual minorities enter older age.
      This research explores results from a nationally representative health survey to
      elucidate some health indicators for older sexual minorities. METHODS: Data from
      the 2013 and 2014 National Health Interview Surveys (NHIS) were pooled for
      increased sample size, and established research methods were followed as
      recommended by prior NHIS sexual orientation studies. We conducted descriptive
      analyses on the differences between SM and heterosexual groups, aged 65 years and
      older, for 12 health indicators. RESULTS: Four out of the 12 health indicators
      were significantly different for sexual minorities, and three out of those four
      indicated positive health outcomes or behaviors when compared with heterosexuals.
      Sexual minorities were more than three times as likely to receive HIV testing as
      heterosexual peers. Sexual minorities were more likely to receive an influenza
      vaccination, and much more likely to report excellent or very good health, than
      their heterosexual peers. Sexual minorities were more than twice as likely to
      report binge drinking, which is consistent with prior research for adult sexual
      minorities. CONCLUSION: This analysis is the first to examine national data on
      health indicators for sexual minorities, aged 65 years and older, using NHIS
      data. As more surveys begin to collect SMdata and more years of data are
      collected by NHIS, a clearer picture of the health of older adult sexual
      minorities should emerge.

PMID- 29028457
TI  - Photocatalytic degradation of P-Cresol using TiO2/ZnO hybrid surface capped with
      polyaniline.
AB  - This study evaluated the photocatalytic activity of polyaniline (PANI)-capped
      titanium dioxide and zinc oxide (TiO2/ZnO) hybrid, for the degradation of P
      Cresol. The hybrid was synthesized by precipitating ZnO on the surface of
      commercial TiO2. An "in situ" chemical oxidative polymerization method was used
      to prepare the PANI capped hybrid (TiO2/ZnO/PANI). The photocatalysts were
      characterized by powder X-ray diffraction (XRD), a Brunauer Emmett Teller (BET)
      analyzer, Fourier-transform infrared (FTIR) and photoluminescence spectroscopies,
      high resolution-transmission electron microscopy (HR-TEM) and thermogravimetric
      analysis (TGA). During photodegradation under ultraviolet (UV) irradiation, ZnO,
      TiO2, TiO2/ZnO hybrid and TiO2/ZnO/PANI composite had P-Cresol removal of 43%,
      50%, 61% and 99%, respectively. The higher activity of the TiO2/ZnO hybrid as
      compared to TiO2 and ZnO was attributed to a reduced electron-hole pair
      recombination. The recombination was further significantly reduced upon
      introduction of PANI; hence, the highest activity observed with TiO2/ZnO/PANI.
      The initial reaction rate constant for TiO2/ZnO/PANI (0.9679 min-1) was more than
      twice compared to that for TiO2/ZnO hybrid (0.1259 min-1). A synergistic effect
      between PANI and TiO2/ZnO resulted in a highly efficient charge separation caused
      by the transfer of photogenerated holes from the hybrid to highest occupied
      molecular orbitals (HOMO) of PANI. The best TiO2/ZnO/PANI (PANI to TiO2/ZnO)
      ratio observed was 0.5:2 for the photodegradation of P-Cresol. Total organic
      carbon (TOC) analysis indicated a 97.4% mineralization of P-Cresol with
      PANI/TiO2/ZnO.

PMID- 29028458
TI  - Exploring gender and elder abuse from the perspective of professionals.
AB  - We conducted an online survey of professionals working in two Canadian provinces
      to learn about their knowledge of elder abuse from a gender-based perspective. A
      total of 169 professionals (90% women) completed a survey in either French or
      English. Five topic areas emerged from the analysis: the influence of gender on
      the risk of abuse; types of abuse detected; knowledge gaps; capacity to respond
      to gender-based abuse; and awareness of resources. To gain further insight into
      these results, we conducted three focus groups with a total of 24 professionals.
      Professionals held relatively little recognition of, or knowledge about, gender
      related to elder abuse. Our results indicate the need to develop educational and
      awareness raising opportunities for professionals who work with abused older
      adults in both French and English to identify and respond to the unique needs of
      older women and men.

PMID- 29028459
TI  - Viral Diagnostics.

PMID- 29028460
TI  - Goldwater Rule: Red Line or Guideline?

PMID- 29028461
TI  - Antibiotic-Impregnated Central Venous Catheters Do Not Change Antibiotic
      Resistance Patterns.
AB  - BACKGROUND: Antibiotic-impregnated central venous catheters (CVCs) decrease the
      incidence of infection in high-risk patients. However, use of these catheters
      carries the hypothetical risk of inducing antibiotic resistance. We hypothesized
      that routine use of minocycline and rifampin-impregnated catheters (MR-CVC) in a
      single intensive care unit (ICU) would change the resistance profile for
      Staphylococcus aureus. METHODS: We reviewed antibiotic susceptibilities of S.
      aureus isolates obtained from blood cultures in a large urban teaching hospital
      from 2002-2015. Resistance patterns were compared before and after implementation
      of MR-CVC use in the surgical ICU (SICU) in August 2006. We also compared
      resistance patterns of S. aureus obtained in other ICUs and in non-ICU patients,
      in whom MR-CVCs were not used. RESULTS: Data for rifampin, oxacillin, and
      clindamycin were available for 9,703 cultures; tetracycline resistance data were
      available for 4,627 cultures. After implementation of MR-CVC use in the SICU,
      rifampin resistance remained unchanged, with rates the same as in other ICU and
      non-ICU populations (3%). After six years of use of MR-CVCs in the SICU, the rate
      of tetracycline resistance was unchanged in all facilities (1%-3%). The use of MR
      CVCs was not associated with any change in S. aureus oxacillin-resistance rates
      in the SICU (66% vs. 60%). However, there was a significant decrease in S. aureus
      clindamycin resistance (59% vs. 34%; p < 0.05) in SICU patients. CONCLUSIONS:
      Routine use of rifampin-minocycline-impregnated CVCs in the SICU was not
      associated with increased resistance of S. aureus isolates to rifampin or
      tetracyclines.

PMID- 29028462
TI  - Older Adults with Alzheimer's Disease Who Have Used an Automatic Medication
      Dispenser for 3 or More Years.
AB  - This article describes four older adults with Alzheimer's disease and
      comorbidities who used an automatic medication dispenser (AMD) to continue
      pharmacotherapy for these chronic diseases and who remained at home living either
      alone or with an older spouse. The AMDs were used for 3 to 4.5 years. The
      patients scored at least 21 on the Mini-Mental State Examination, and their
      dosing regimen involved taking the medication once or twice per day throughout
      this period. The caregivers filled the devices with medications once every 1 to 2
      weeks and continuously monitored the patients' conditions nearly every day.
      Additionally, one caregiver changed how the device is used to accommodate a
      participant's conditions. As a result of using the device, medication adherence
      remained good, and caregiver burden was reduced. The results indicate that an AMD
      can be used as a long-term medication management tool for some older adults with
      dementia when caregivers provide continued support, as described above. Further
      research is needed to clarify the necessary conditions for using an AMD and to
      identify benefits for older adults with dementia to use AMDs to take medication
      on a long-term basis.

PMID- 29028463
TI  - Assessing adult attention deficit hyperactivity disorder (ADHD) in the university
      setting.
AB  - OBJECTIVE: To address the increasing demand for assessments of Adult Attention
      Deficit Hyperactivity Disorder (ADHD), the primary author developed a protocol
      for Counseling and Psychological Services (CAPS) at Stanford University's Vaden
      Student Health Center to improve the efficiency of such evaluations.
      PARTICIPANTS: As part of quality assurance, we reviewed the charts of Stanford
      students who sought assessment for ADHD before the protocol was implemented
      (September 2011-June 2013) and after the protocol was established (October 2013
      August 2014). An IRB exemption was obtained. METHODS: The protocol includes
      questionnaires that solicit detailed clinical information from a variety of
      sources prior to the student's initial visit. RESULTS: A peer chart review of 35
      randomly selected charts showed that students completing the protocol are
      receiving a more thorough assessment. CONCLUSION: The new Stanford ADHD protocol,
      designed to improve clinic efficiency, also increases the availability of
      relevant clinical information.

PMID- 29028464
TI  - Should Physicians Consider the Environmental Effects of Prescribing Antibiotics?
AB  - Pharmaceuticals are beginning to receive attention as a source of pollution in
      aquatic environments. Yet the impact of physician prescription patterns on water
      resources is not often discussed in clinical decision making. Here, we comment on
      a case in which empiric antibiotic treatment might benefit a patient while
      simultaneously being detrimental to the aquatic environment. We first highlight
      the potential harm caused by this prescription from its production to its
      disposal. We then suggest that Van Rensselaer Potter's original conceptualization
      of bioethics can be used to balance clinicians' obligations to protect
      individual, public, and environmental health.

PMID- 29028465
TI  - Cultivating Humility and Diagnostic Openness in Clinical Judgment.
AB  - In this case, a physician rejects a patient's concerns that tainted water is
      harming the patient and her community. Stereotypes and biases regarding
      socioeconomic class and race/ethnicity, constraining diagnostic frameworks, and
      fixed first impressions could skew the physician's judgment. This paper
      narratively illustrates how cultivating humility could help the physician truly
      hear the patient's suggestions. The discussion builds on the multifaceted concept
      of cultural humility as a lifelong journey that addresses not only stereotypes
      and biases but also power inequalities and community inequities. Insurgent
      multiculturalism is a complementary concept. Through epistemic humility-which
      includes both intellectual and emotional components-and admitting uncertainty,
      physicians can enhance patients' and families' epistemic authority and health
      agency.

PMID- 29028466
TI  - Is Acute Care-Oriented Research Ethical in Resource-Limited Settings?
AB  - In this case scenario, a medical student, Jenny, is conducting congenital heart
      disease research in a resource-limited setting faced with water insecurity. She
      has concerns about how ethical it is for her to conduct advanced clinical
      research in a region with more basic health needs. The first commentary argues
      that advanced clinical research in resource-limited settings follows the ethical
      principle of beneficence and interactional justice but violates the principle of
      distributive justice. The second commentary questions whether beneficence is
      enough, since the Belmont Report states that beneficence is the obligation to
      simultaneously reduce harm and increase benefit. It calls upon public health
      physician-scientists to think deeply about how to involve communities in their
      research-and how to insert themselves into health policy development processes.

PMID- 29028467
TI  - Expanding Ethics Review Processes to Include Community-Level Protections: A Case
      Study from Flint, Michigan.
AB  - As the Flint community endeavors to recover and move forward in the aftermath of
      the Flint water crisis, distrust of scientific and governmental authorities must
      be overcome. Future community engagement in research will require community-level
      protections ensuring that no further harm is done to the community. A community
      ethics review explores risks and benefits and complements institutional review
      board (IRB) review. Using the case of Flint, I describe how community-level
      ethical protections can reestablish a community's trust. All IRBs reviewing
      protocols that include risk to communities and not merely individual participants
      should consider how community members are engaged in the proposed research and
      identify and respond to questions and domains of concern from community members.

PMID- 29028468
TI  - Lessons for Physicians from Flint's Water Crisis.
AB  - Physicians form a vital front in recognizing unusual clinical presentations that
      could herald a health threat. In the Flint water crisis, physicians can be
      credited with playing critical roles in both uncovering the crisis and providing
      leadership when government failed to respond effectively. Yet most physicians in
      Flint were not formally trained in advocacy or leadership and might have
      recognized the health implications of the crisis more quickly had they received
      formal environmental health training. Furthermore, connections to other
      professional disciplines-and to the community-are vital for effective responses
      to environmental health threats. We explore some lessons learned in Flint that
      might help expedite resolution of future environmental health crises,
      particularly those involving aging infrastructure and diminished or dysfunctional
      regulation or oversight.

PMID- 29028469
TI  - The Importance of Clinicians and Community Members Receiving Timely and Accurate
      Information about Waterborne Hazards.
AB  - It is important for clinicians and community members to receive up-to-date
      information about the microbiological and elemental composition of local water
      supplies. Clinicians play an important role in helping their patients to
      interpret water quality data and understand the potential impact of water quality
      on their health. Expanding the medical school curriculum to include environmental
      health, public health, and health disparities-including disparities related to
      environmental quality and waterborne hazards-is key to clinicians' fulfilling
      this role.

PMID- 29028470
TI  - The Safe Drinking Water Act of 1974 and Its Role in Providing Access to Safe
      Drinking Water in the United States.
AB  - In 1974, President Gerald Ford signed into law the Safe Drinking Water Act, the
      first piece of legislation of its kind to provide a comprehensive regulatory
      framework for overseeing the nation's drinking water supply. The law has proven
      instrumental in setting standards for ensuring that the US population can access
      drinking water that is safe. However, the law delegates much of its monitoring
      requirements to states, creating, at times, a confusing and complicated system of
      standards that must be adhered to and enforced. Although it has proven valuable
      in the safety standards it specifies, the law's administration and enforcement
      poses tremendous challenges.

PMID- 29028471
TI  - Water Safety and Lead Regulation: Physicians' Community Health Responsibilities.
AB  - This article reviews the regulation of lead in drinking water, highlighting its
      epidemiological, engineering, and ethical aspects with a focus on the Flint water
      crisis. We first discuss water quality policy and its implementation with a focus
      on lead contamination of water, primarily from pipe systems between a water
      treatment facility and a tap. We then discuss physicians' roles and ethical
      responsibilities regarding safe drinking water using a human rights framework. We
      argue that physicians can play an important role in safeguarding drinking water
      in their communities by being vigilant, honoring the community's trust in them,
      and warning, educating, and empowering patients and broader communities so as to
      protect tap water safety and public health.

PMID- 29028472
TI  - Waterborne.
AB  - These photos capture the Flint water crisis from the perspective of a
      photographer and cinematographer who is a resident of Flint. They represent
      citizens' struggles, town hall meetings, and some of the city's repair efforts.
      They also illuminate environmental injustice as a violation of human rights.

PMID- 29028473
TI  - Elder Self-Neglect: Another Ethical Dilemma for Physicians.

PMID- 29028474
TI  - Capacity Determinations and Elder Self-Neglect.

PMID- 29028475
TI  - Response to "What Should Physicians Do When They Disagree, Clinically and
      Ethically, with a Surrogate's Wishes?"

PMID- 29028479
TI  - Peer Review in Scientific Scholarship.

PMID- 29028477
TI  - Modulation of the NF-kappaB signaling pathway by the HIV-2 envelope glycoprotein
      and its incomplete BST-2 antagonism.
AB  - The HIVs have evolved by selecting means to hijack numerous host cellular
      factors. HIVs exploit the transcription factor NF-kappaB to ensure efficient LTR
      driven gene transcription. However, NF-kappaB is primarily known to act as a key
      regulator of the proinflammatory and antiviral responses. Interestingly,
      retroviruses activate NF-kappaB during early stages of infection to initiate
      proviral genome expression while suppressing it at later stages to restrain
      expression of antiviral genes. During HIV-1 infection, diverse viral proteins
      such as Env, Nef and Vpr have been proposed to activate NF-kappaB activity,
      whereas Vpu has been shown to inhibit NF-kappaB activation. It is still unclear
      how HIV-2 regulates NF-kappaB signaling pathway during its replication cycle.
      Here we confirm that human BST-2 and HIV-1 Env proteins can trigger potent
      activation of NF-kappaB. Importantly, we demonstrate for the first time that the
      HIV-2 Env induces NF-kappaB activation in HEKappa293T cells. Furthermore, the
      anti-BST-2 activity of the HIV-2 Env is not sufficient to completely inhibit NF
      kappaB activity.

PMID- 29028476
TI  - Differential interaction between human and murine Crm1 and lentiviral Rev
      proteins.
AB  - Mice have multiple obstacles to HIV replication, including a block of unspliced
      and partially spliced viral mRNA nuclear export. In human, Rev binds to the Rev
      response element and human (h) Crm1, facilitating nuclear export of RRE
      containing viral RNAs. Murine (m) Crm1 is less functional than hCrm1 in this
      regard. Here we demonstrated that in biochemical experiments mCrm1 failed to
      interact with HIV Rev whereas hCrm1 did. In genetic experiments in human cells,
      we observed a modest but significant differential effect between mCrm1 and hCrm1,
      which was also true of other lentiviral Revs tested. Triple mutant hCrm1 P411T
      M412V-F414S behaved similarly to mCrm1, whereas mCrm1 with T411P-V412M-S414F
      regained some activity, although contribution of additional residues to its
      function can not be excluded. Similar results were observed in murine cells. This
      suggests a differential interaction between hCrm1 and mCrm1 and many lentiviral
      Revs, which may partially explain the HIV replicative defect in mice.

PMID- 29028480
TI  - WITHDRAWN: Revisiting the cholinergic hypothesis in Alzheimer's disease: Emerging
      evidence from translational and clinical research.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
      business/policies/article-withdrawal.

PMID- 29028481
TI  - Neuropsychiatric symptoms as risk factors of dementia in a Mexican population: A
      10/66 Dementia Research Group study.
AB  - INTRODUCTION: Cognitive and/or memory impairment are the main clinical markers
      currently used to identify subjects at risk of developing dementia. This study
      aimed to explore the relationship between the presence of neuropsychiatric
      symptoms and dementia incidence. METHODS: We analyzed the association between
      neuropsychiatric symptoms and incident dementia in a cohort of 1355 Mexican older
      adults from the general population over 3 years of follow-up, modeling cumulative
      incidence ratios using Poisson models. RESULTS: Five neuropsychiatric symptoms
      were associated with incident dementia: delusions, hallucinations, anxiety,
      aberrant motor behavior, and depression. The simultaneous presence of two
      symptoms had a relative risk, adjusted for mild cognitive impairment, diabetes,
      indicators of cognitive function, and sociodemographic factors, of 1.9 (95%
      confidence interval, 1.2-2.9), whereas the presence of three to five, similarly
      adjusted, had a relative risk of 3.0 (95% confidence interval, 1.9-4.8).
      DISCUSSION: Neuropsychiatric symptoms are common in predementia states and may
      independently contribute as risk factors for developing dementia.

PMID- 29028482
TI  - Adiposity phenotypes are associated with type-2 diabetes: LAP index, body
      adiposity index, and neck circumference.
AB  - BACKGROUND AND AIMS: Adiposity phenotypes can be detected by anthropometric
      indexes associated with type-2 diabetes mellitus (T2DM). Besides body mass index
      (BMI) and waist circumference (WC), new indices seem to be able to identify T2DM.
      This study aimed to evaluate independent associations of T2DM with lipid
      accumulation product (LAP index), neck circumference (NC) and body adiposity
      index (BAI) in patients with hypertension. METHODS: A cross-sectional study was
      carried out among 430 patients with hypertension. The T2DM diagnosed was
      standardized. WC and NC (cm) were measured and BMI was calculated. LAP index was
      calculated separately for men [(WC-65) * TG] and women [(WC-58) * TG]; BAI was
      evaluated in percentiles according to hip (cm)/[height (m)1.5]-18. RESULTS:
      Participants were aged 58.3 +/- 11.7 years, had systolic blood pressure (SBP)
      154.2 +/- 24.9 mmHg, diastolic blood pressure (DBP) 89.0 +/- 14.7 mmHg, and BMI
      30.1 +/- 6.0 kg/m2. There was 145 men and 285 women, and 142 participants had
      T2DM. Analyses carried out separately by gender showed that among men, BAI at the
      75th percentile increased about 60% the risk of T2DM, while among women, those in
      the upper quartile of LAP and NC had increased risk of T2DM (prevalence ratio
      (PR): 2.93; 95%CI: 1.62-5.28 and 3.30; 95%IC: 1.78-6.14, respectively), after
      adjustment for potential confounders. CONCLUSIONS: Adiposity phenotypes such as
      LAP index and neck circumference were independently associated with T2DM in
      hypertensive women, and BAI was associated with T2DM in men.

PMID- 29028483
TI  - Circulating levels of sgp130 and sex hormones in male patients with coronary
      atherosclerotic disease.
AB  - BACKGROUND AND AIMS: Inflammation and endocrine disorders are considered as major
      pathogenic factors of coronary atherosclerotic disease (CAD). Sgp130, a natural
      antagonist of IL-6 trans-signaling, and sex hormones, especially testosterone and
      estradiol, are prominently considered as anti-atherosclerotic. The aim of this
      study was to investigate the possible association between serum sgp130 and
      testosterone and estradiol in male CAD patients. METHODS: A total of 254 male
      patients with CAD and 122 male controls were recruited for this study.
      Circulating IL-6, sIL-6, sgp130 were measured by an enzyme-linked immunosorbent
      assay. Serum concentrations of hs-CRP, testosterone, estradiol, and other routine
      biochemical markers were also quantified. Besides, we observed the effects of
      testosterone and estradiol on sgp130 in HUVECs. RESULTS: Serum levels of sgp130,
      testosterone and estradiol and the ratio of testosterone and estradiol (T/E2)
      were obviously decreased in CAD patients compared with controls. Pearson
      correlation analysis showed that serum sgp130 levels had positive correlations
      with testosterone (r = 0.295, p < 0.001) and estradiol (r = 0.338, p < 0.001)
      levels in CAD patients. In addition, multiple regression analysis indicated that
      serum sgp130 was positively associated with estradiol (beta-coefficient = 0.450,
      p < 0.001) and T/E2 ratio (beta-coefficient = 0.257, p = 0.001). Furthermore,
      basic studies found that supernatant sgp130 levels of HUVECs were significantly
      increased by the cooperativity of testosterone and estradiol. CONCLUSIONS: Low
      levels of serum sgp130 were positively associated with sex hormones in male
      patients with CAD, suggesting an important role of sgp130 in the presence of low
      and imbalanced sex hormones levels. Thus, regulation of sgp130 levels by
      rebalancing sex hormones has the potential to be a novel therapeutic for the
      treatment of CAD.

PMID- 29028484
TI  - Cholesterol target value attainment and lipid-lowering therapy in patients with
      stable or acute coronary heart disease: Results from the Dyslipidemia
      International Study II.
AB  - BACKGROUND AND AIMS: Low-density lipoprotein cholesterol (LDL-C) is a major
      contributor to cardiovascular disease. In the Dyslipidemia International Study II
      (DYSIS II), we determined LDL-C target value attainment, use of lipid-lowering
      therapy (LLT), and cardiovascular outcomes in patients with stable coronary heart
      disease (CHD) and those suffering from an acute coronary syndrome (ACS). METHODS:
      DYSIS II included patients from 18 countries. Patients with either stable CHD or
      an ACS were enrolled if they were >=18 years old and had a full lipid profile
      available. Data were collected at a physician visit (CHD cohort) or at hospital
      admission and 120 days later (ACS cohort). RESULTS: A total of 10,661 patients
      were enrolled, 6794 with stable CHD and 3867 with an ACS. Mean LDL-C levels were
      low at 88 mg/dl and 108 mg/dl for the CHD and ACS cohorts respectively, with only
      29.4% and 18.9% displaying a level below 70 mg/dl. LLT was utilized by 93.8% of
      the CHD cohort, with a mean daily statin dosage of 25 +/- 18 mg. The proportion
      of the ACS cohort treated with LLT rose from 65.2% at admission to 95.6% at
      follow-up. LLT-treated patients, who were female, obese, or current smokers, were
      less likely to achieve an LDL-C level of <70 mg/dl, while those with type 2
      diabetes, chronic kidney disease, or those taking a higher statin dosage were
      more likely. CONCLUSIONS: Few of these very high-risk patients achieved the LDL-C
      target, indicating huge potential for improving cardiovascular outcome by use of
      more intensive LLT.

PMID- 29028485
TI  - A study on beta-glucan binding protein (beta-GBP) and its involvement in
      phenoloxidase cascade in Indian white shrimp Fenneropenaeus indicus.
AB  - The present study reports the purification of novel immune molecule beta-1, 3
      glucan binding protein from the heamolymph of the Indian white shrimp,
      Fenneropenaeus indicus (Fibeta-GBP). The purified Fibeta-GBP had 95kDa molecular
      weight in SDS-PAGE analysis. MALDI-TOF/TOF analysis revealed that the purified
      Fibeta-GBP showed similarity to various crustacean proteins; 48 and 46%
      similarity was observed for beta-1, 3 glucan binding protein of Chinese white
      shrimp Fenneropenaeus chinensis and banana shrimp Fenneropenaeus merguiensis,
      with MOWSE score of 3.11e+12 and 2.05e+8, respectively. The phenoloxidase
      activity (PO) of Fibeta-GBP was evaluated and, in the presence of laminarin, PO
      activity increased significantly. Substrate specificity assay demonstrated that
      Fibeta-GBP had the specific binding site for soluble or insoluble beta-glucan
      (laminarin), since the PO activity increased in the presence of laminarin when
      compared to other sugars. Enzymatic activities revealed that the optimum
      temperature and pH for Fibeta-GBP activating PO were 40 degrees C and pH 7-8.
      Moreover, even at 100 degrees C Fibeta-GBP enhanced PO activity highlighting that
      Fibeta-GBP was thermostable and thermophilic in nature. Among various divalent
      metallic ions, Fibeta-GBP significantly promoted the PO activity in presence of
      Mg2+ and Ca2+. The breakdown of para nitroanilide from Nalpha-Benzoyl-l-Arginine
      4-Nitroanilide hydrochloride showed that serine protease activity was induced by
      Fibeta-GBP and also increased concentration of Fibeta-GBP evoked the activity.
      Furthermore, hemolytic activity tests revealed that PO reaction product induced
      RBC membrane damage and cell shrinkage. Lastly, Baclight bacterial viability
      assays showed maximum killing effect of PO reaction product on both Gram positive
      and Gram negative bacteria.

PMID- 29028486
TI  - A point mutation in the extracellular domain of CD4 completely abolishes CD4 T
      cell development in C57BL/6 mouse.
AB  - In this study, we performed ENU mutagenesis and multi-parameter flow cytometric
      analysis in C57BL/6 mice to uncover novel genes or alleles regulating immune cell
      development. We identified a novel mutant allele of Cd4 gene which completely
      blocked development of a major subset of T cells named CD4 T cell. Our data for
      the first time showed experimentally in mice the critical role of the first
      extracellular domain, by obtaining mice with a loss of function mutation from Ile
      to Asn at the position 99 of CD4 (I99N). Interestingly, such CD4I99N mutant
      protein can be expressed on the surface of human cells, and the mRNA stability
      could be also affected by this point mutation, suggesting that absence of CD4 T
      cells in mice rooted in the deficiency in function and expression of CD4. In
      addition, we used this novel CD4 T cell deficient model as recipient mice for
      adoptive transfer experiment, and showed that it could be an optimal model for
      study of CD4 T cells.

PMID- 29028487
TI  - Ziram, a dithiocarbamate fungicide, exhibits pseudo-cytoprotective actions
      against oxidative stress in rat thymocytes: Possible environmental risks.
AB  - Ziram, a dithiocarbamate fungicide, protects various vegetables and fruits
      against infections by fungus. Recently, there have been increasing anxieties
      about the risks in the use of dithiocarbamate fungicides. Our previous studies
      showed that Zn2+ was a determinant of Ziram cytotoxicity. In addition, Zn2+ is
      linked to H2O2 cytotoxicity. Therefore, in this study, we aimed to test the
      hypothesis that Ziram could augment the cytotoxicity of H2O2 by examining the
      changes induced by Ziram in some cellular parameters in rat thymic lymphocytes
      subjected to H2O2-induced oxidative stress using flow-cytometric methods with
      fluorescent dyes. Ziram significantly attenuated H2O2-induced cell death at
      sublethal concentrations. However, in the cells under oxidative stress elicited
      by H2O2, Ziram promoted the changing over from intact cells to living cells with
      exposed phosphatidylserine (PS) on plasma membranes, whereas it inhibited the
      transition from PS-exposed living cells to dead cells. Ziram significantly
      augmented H2O2 actions, including reduction of cellular glutathione levels and
      elevation of intracellular Zn2+ concentrations. Conversely, it attenuated H2O2
      induced depolarization of mitochondrial membrane potential. Ziram at sublethal
      concentrations seems to exhibit promotive and suppressive actions on the process
      of cell death caused by H2O2. Ziram increased the number of living cells with
      exposed PS, a phenomenon characteristic of early stages of apoptosis. Thus, it is
      concluded that Ziram exhibits pseudo-cytoprotective actions against H2O2-induced
      oxidative stress. Ziram at sublethal concentrations exerts promotive and
      suppressive actions on the process of cell death caused by oxidative stress.

PMID- 29028489
TI  - Assessment of types of synthetic cannabinoids in narcotic cases assessed by the
      Council of Forensic Medicine between 2011-2015, Ankara, Turkey.
AB  - Synthetic cannabinoids mimic the effects of cannabis and are the largest and
      fastest growing class of newly appearing designer drugs. Reports have revealed
      that various types of synthetic cannabinoids are mixed with herbal substances.
      The present study investigated the herbal substance cases involving synthetic
      cannabinoids in Ankara and nearby cities in Turkey. Data were collected from the
      reports of synthetic cannabinoids that were analyzed between January 01, 2011 and
      December 31, 2015 in the Ankara Narcotic Department of the Council of Forensic
      Medicine at the request of the judicial authorities. In all, 4610 narcotic
      reports were obtained and reviewed. Among these narcotic reports during the
      period, 370 reports (8%) were related to synthetic cannabinoids. 28 synthetic
      cannabinoid compounds could be identified in herbals: 5-F-AB-PINACA, 5-F-AKB-48,
      5-F-NNEI, 5-F-PB-22, AB-CHMINACA, AB-FUBINACA, AB-PINACA, ADB-CHMINACA, ADB
      FUBINACA, AKB-48, AM-2201, EAM-2201, JWH-018, JWH-022, JWH-031, JWH-122, JWH-201,
      JWH-210, JWH-250, JWH-251, JWH-307, MAM-2201, NM-2201, PB-22, RCS-4, THJ-2201, UR
      144, XLR-11. The amount of herbals was 30.72g, 329.22g, 665.89g, 4844.7g, and
      5684.3g in 2011, 2012, 2013, 2014, and 2015, respectively. Generally, herbals
      contained more than one synthetic cannabinoids. ADB-FUBINACA was the most common
      synthetic cannabinoid among the herbals determined in this study, which was
      3132.43g, excepting multi-synthetic cannabinoid herbals. The amount and diversity
      of synthetic cannabinoid compounds have increased dramatically between 2011 and
      2015.

PMID- 29028488
TI  - Prenatal phthalate exposure and placental size and shape at birth: A birth cohort
      study.
AB  - OBJECTIVE: There is concern over the potential placental effects of prenatal
      phthalate exposure, and the potential adverse effects of prenatal phthalate
      exposure require further study; however, few data are available in humans. We
      investigated the associations between phthalate exposure in each trimester and
      both placental size and shape at birth. METHODS: We measured the urinary
      concentrations of phthalate metabolites among 2725 pregnant women in the
      Ma'anshan Birth Cohort. Before collecting urine samples from each of the three
      trimesters, the pregnant women were interviewed via questionnaires. Placental
      information was obtained from hospital records. We estimated the sex-specific
      associations between urinary phthalate concentrations in each trimester and both
      placental size and shape at birth using adjusted multiple regression. A linear
      mixed model was used for the repeated measures analysis with subject-specific
      random intercepts and slopes for gestational age at sample collection to test the
      effect of phthalate levels on placental size and shape and to estimate the effect
      sizes. RESULTS: Overall, placental breadth increased by 0.148cm (95% CI: 0.078,
      0.218) with each 1 ln-concentration increase in MBP in the first trimester. The
      difference between placental length and breadth (length-breadth) decreased by
      0.086cm (95% CI: -0.159, -0.012) and 0.149cm (95% CI: -0.221, -0.076) with each 1
      ln-concentration increase in MMP and MBP, respectively, in the first trimester.
      In the second trimester, placental thickness increased by 0.017cm (95% CI: 0.006,
      0.027), 0.020cm (95% CI: 0.004, 0.036), 0.028cm (95% CI: 0.007, 0.048), and
      0.035cm (95% CI: 0.018, 0.053) with each 1 ln-concentration increase in MMP, MBP,
      MEOHP, and MEHHP, respectively. In the third trimester, placental thickness
      increased by 0.037cm (95% CI: 0.019, 0.056) and 0.019cm (95% CI: 0, 0.037) with
      each 1 ln-concentration increase in MBP and MEHP, respectively. Multiple linear
      regression for each offspring sex indicated that prenatal phthalate exposure
      increased placental thickness in both the first and second trimesters in males,
      whereas the corresponding relationship was close to null in females. Linear mixed
      models (LMMs) yielded similar results. CONCLUSION: Our results suggest the
      presence of associations between prenatal phthalate exposure and placental size
      and shape. Exposure to certain phthalates may cause the placenta to become
      thicker and more circular. Associations appeared stronger for the subsample
      representing male offspring than those for the subsample representing female
      offspring. Given the few studies on this topic, additional research is warranted.

PMID- 29028490
TI  - Differentiation of red lipsticks using the attenuated total reflection technique
      supported by two chemometric methods.
AB  - The main challenge for the identification and differentiation of lipsticks for
      forensic purposes is the fact that they have a similar chemical composition - in
      particular, samples of the same hue. The objective of the presented research was
      to solve this problem using a nondestructive analytical technique - attenuated
      total reflection spectroscopy (ATR). 38 red lipsticks produced by 20 different
      manufacturers were examined in optimized experimental conditions. To facilitate
      discrimination and provide more extensive analyses of the obtained data, two
      chemometric techniques: principal component analysis and cluster analysis were
      used. Ultimately, nine groups of investigated lipstick samples with comparable
      chemical compositions were differentiated. Moreover, lipstick smears on six
      different interfering surfaces were analyzed and spectral subtraction was
      performed in order to identify individual samples. The established approach
      succeeded in identifying the index number and the manufacturer of the samples by
      using an in-lab built ATR spectra library. The developed method demonstrates a
      great potential for the differentiation and identification of red lipsticks with
      a very similar hue. It also seems to have good prospects for future application
      in forensic science investigations.

PMID- 29028491
TI  - Boron removal from hydraulic fracturing wastewater by aluminum and iron
      coagulation: Mechanisms and limitations.
AB  - One promising water management strategy during hydraulic fracturing is treatment
      and reuse of flowback/produced water. In particular, the saline flowback water
      contains many of the chemicals employed for fracking, which need to be removed
      before possible reuse as "frac water." This manuscript targets turbidity along
      with one of the additives; borate-based cross-linkers used to adjust the
      rheological characteristics of the frac-fluid. Alum and ferric chloride were
      evaluated as coagulants for clarification and boron removal from saline flowback
      water obtained from a well in the Eagle Ford shale. Extremely high dosages (>
      9000 mg/L or 333 mM Al and 160 mM Fe) corresponding to Al/B and Fe/B mass ratios
      of ~70 and molar ratios of ~28 and 13 respectively were necessary to remove ~80%
      boron. Hence, coagulation does not appear to be feasible for boron removal from
      high-strength waste streams. X-ray photoelectron spectroscopy revealed BO bonding
      on surfaces of freshly precipitated Al(OH)3(am) and Fe(OH)3(am) suggesting boron
      uptake was predominantly via ligand exchange. Attenuated total reflection-Fourier
      transform infrared spectroscopy provided direct evidence of inner-sphere boron
      complexation with surface hydroxyl groups on both amorphous aluminum and iron
      hydroxides. Only trigonal boron was detected on aluminum flocs since possible
      presence of tetrahedral boron was masked by severe AlO interferences. Both
      trigonal and tetrahedral conformation of boron complexes were identified on
      Fe(OH)3 surfaces.

PMID- 29028492
TI  - Modelling an industrial anaerobic granular reactor using a multi-scale approach.
AB  - The objective of this paper is to show the results of an industrial project
      dealing with modelling of anaerobic digesters. A multi-scale mathematical
      approach is developed to describe reactor hydrodynamics, granule
      growth/distribution and microbial competition/inhibition for substrate/space
      within the biofilm. The main biochemical and physico-chemical processes in the
      model are based on the Anaerobic Digestion Model No 1 (ADM1) extended with the
      fate of phosphorus (P), sulfur (S) and ethanol (Et-OH). Wastewater dynamic
      conditions are reproduced and data frequency increased using the Benchmark
      Simulation Model No 2 (BSM2) influent generator. All models are tested using two
      plant data sets corresponding to different operational periods (#D1, #D2).
      Simulation results reveal that the proposed approach can satisfactorily describe
      the transformation of organics, nutrients and minerals, the production of
      methane, carbon dioxide and sulfide and the potential formation of precipitates
      within the bulk (average deviation between computer simulations and measurements
      for both #D1, #D2 is around 10%). Model predictions suggest a stratified
      structure within the granule which is the result of: 1) applied loading rates, 2)
      mass transfer limitations and 3) specific (bacterial) affinity for substrate.
      Hence, inerts (XI) and methanogens (Xac) are situated in the inner zone, and this
      fraction lowers as the radius increases favouring the presence of acidogens
      (Xsu,Xaa, Xfa) and acetogens (Xc4,Xpro). Additional simulations show the effects
      on the overall process performance when operational (pH) and loading (S:COD)
      conditions are modified. Lastly, the effect of intra-granular precipitation on
      the overall organic/inorganic distribution is assessed at: 1) different times;
      and, 2) reactor heights. Finally, the possibilities and opportunities offered by
      the proposed approach for conducting engineering optimization projects are
      discussed.

PMID- 29028493
TI  - Zeolite-supported nanoscale zero-valent iron: New findings on simultaneous
      adsorption of Cd(II), Pb(II), and As(III) in aqueous solution and soil.
AB  - Nanoscale zero-valent iron (NZVI) has a high adsorption capacity for heavy
      metals, but it forms aggregates easily. In this study, zeolite-supported
      nanoscale zero-valent iron (Z-NZVI) was synthesized from a simplified liquid
      phase reduction of iron(III) salts which simultaneously adsorbed As(III), Cd(II)
      and Pb(II) from aqueous solution and soil. Scanning electron micrographs showed
      that aggregation was eliminated and the NZVI evenly dispersed onto the surface of
      zeolite. FTIR spectra reveal that NZVI was protected from oxidization on the
      surface of Z-NZVI. XRD and XPS patterns confirmed the formation of Cd(OH)2, Pb0,
      and FeAsO4 in Z-NZVI after adsorption. The experimental maximum adsorption
      capacity of Z-NZVI was 11.52mg As(III)/g, 48.63mg Cd(II)/g, and 85.37mg Pb(II)/g
      at pH 6, respectively, much higher than that of zeolite. Batch experiments
      indicate that various adsorption mechanisms including electrostatic adsorption,
      ionic exchange, oxidation, reduction, co-precipitation, and complexation
      coexisted with the selected heavy metals. Due to the formation of multiphase
      compounds on the Z-NZVI, the synergy and competition among heavy metals were
      concurrent. Most arsenic, cadmium and lead in the soil samples were immobilized
      after mixing with 30g/kg Z-NZVI. These results suggest that Z-NZVI has great
      potential for treating water and soil multi-contaminated with heavy metals.

PMID- 29028494
TI  - Surfactants selectively reallocated the bacterial distribution in soil
      bioelectrochemical remediation of petroleum hydrocarbons.
AB  - Soil contaminated by aged petroleum hydrocarbons is faced with scarcity of
      electron acceptors, low activity of functional microbes and inefficient electron
      transfer, which hinder the bioremediation application. The soil microbial fuel
      cell (MFC) simultaneously solves these problems with bioelectricity production.
      In this study, five types of surfactants were introduced to enhance the
      bioavailability of aged petroleum hydrocarbon in soils. The ampholytic surfactant
      (lecithos) was optimal due to the highest bioelectricity generation (0.321Cd-1g
      1) and promoted hydrocarbon degradation (328%), while the nonionic (glyceryl
      monostearate) and cationic (cetyltrimethylammonium bromide) surfactants were
      inefficient. The surfactants induced a special microbial enrichment affiliated
      with Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Chloroflexi,
      Planctomycetes and Acidobacteria (93%-99% of total) in soil MFCs. The anionic
      surfactant (sodium dodecyl sulfate) exhibited the strongest selectivity, and
      alpha-proteobacteria and gamma-proteobacteria abundances decreased while
      Clostridia increased, much like the result obtained with the biosurfactant beta
      cyclodextrin. Furthermore, Bacillus abundance was increased in connected soil
      MFCs, except addition of lecithos in which Clostridium increased to 14.88% from
      3.61% in the control. The high correlations among Bacillus, Phenylobacterium,
      Solibacillus (0.9162-0.9577) and among Alcaligenes, Dysgonomonas, Sedimentibacter
      (0.9538-0.9966) indicated a metabolic network of microorganisms in the soil
      bioelectrochemical remediation system.

PMID- 29028495
TI  - Non-cytotoxic effect of green synthesized silver nanoparticles and its
      antibacterial activity.
AB  - Silver nanoparticles (AgNPs) were green synthesized using ethanolic extract of
      fenugreek leaves and characterized using UV-Vis spectroscopy, Fourier transform
      infra-red spectroscopy (FTIR), X-ray diffraction (XRD), high resolution
      transmission electron microscopy HRTEM and energy dispersive X-ray analysis (EDX)
      techniques. The HRTEM results revealed the formation of highly stable, mono
      dispersed, spherical shaped AgNPs with the size ranging from 20 to 30nm. The
      presence of flavonoids and their interaction with the AgNPs were confirmed using
      FTIR. Antibacterial activities of the AgNPs were studied against pathogenic gram
      positive Staphylococcus aureus (S. aureus) and gram negative Escherichia coli (E.
      coli) bacteria. The synthesized AgNPs displayed the enhancement of antibacterial
      activity against E. coli. The morphological changes in the bacterial cell
      membrane was observed using SEM analysis. Leakage of protein from the bacterial
      cells increased at every time intervals (2 and 4h). MTT assay was carried out for
      the AgNPs against human skin cell line (HaCaT). Interestingly, cytotoxicity of
      the synthesized AgNPs was less toxic to HaCaT cells as compared to bacteria
      cells, which suggests that the synthesized AgNPs by this method is eco-friendly
      in nature.

PMID- 29028496
TI  - Are the damaging effects induced by the imazethapyr formulation Pivot(r) H in
      Boana pulchella (Anura) reversible upon ceasing exposure?
AB  - In the present study, the damage recovery capabilities of Boana pulchella
      tadpoles after acute exposure (96h) to 0.39mg/L concentration of the imazethapyr
      (IMZT)-based herbicide formulation Pivot(r) H (25% IMZT LC50 value) were assessed
      during a period of 7 to -21 days. To appraise the recovery capabilities,
      frequency of micronuclei (MNs), other nuclear abnormalities and DNA single-strand
      breaks evaluated by single cell gel electrophoresis assay on circulating blood
      cells were employed as endpoints for genotoxicity. Growth, development, body
      mass, and morphological abnormalities were also employed as individual endpoints
      in the recovery assay. Results demonstrated that IMZT induced sublethal effects
      at both the individual (i.e., loss of keratodonts) and cytogenetic levels (e.g.,
      increase of MN frequency, other nuclear abnormalities and DNA single-strand
      breaks). At 11 days of the exposure phase, tadpoles recovered their basal levels
      of frequency of MNs, other nuclear abnormalities, and comets. However, loss of
      keratodonts, observed at the end of the exposure period, was present up to 21
      days thereafter. Finally, axial abnormalities and delay in development stage were
      observed only during the postexposure phase in IMZT-exposed tadpoles at 18 and 25
      days, respectively and were observed until the end of the experiment. This is the
      first evidence of use the comet assay as cytogenetic biomarker of genotoxicity in
      evaluating the recovery capabilities of amphibians in general and also those of
      B. pulchella after exposure to IMZT.

PMID- 29028497
TI  - Aquatic macroinvertebrate assemblages are affected by insecticide applications on
      the Argentine Pampas.
AB  - Agriculture intensification in Argentina has increased agrochemicals consumption
      in the last decades and might represent an environmental risk for adjacent water
      bodies. The objective of the present work was to assess the effect of land use on
      water quality and invertebrate assemblages in the Argentine Pampas streams. Eight
      streams were sampled on 4 occasions during the 2013/14 growing season. Three
      streams are located within a biosphere reserve, two drain basins with extensive
      livestock fields, and three run through intensively cultivated plots; one of them
      contained a 30m wide uncultivated grass-covered strip between the crop and the
      stream. Macroinvertebrates were sampled from emergent vegetation by means of a D
      net with a 500um pore size, and 30cm diameter. Higher nutrient concentrations
      were measured in the agricultural streams. Endosulfan was measured in sediments
      of the agricultural streams, concentrations being significantly lower in the
      stream with the buffer strip. Invertebrate assemblages in the cropped streams
      were significantly different from those in the livestock and reserve streams,
      those in the latter not being different from each other. Ampullaridae (Pomacea
      canaliculata) and Planorbidae (Biomophalaria peregrina) were the taxa best
      represented in the agricultural streams. Hyalellidae (Hyalella curvispina),
      Zygoptera and Planorbidae (B. peregrina) were the taxa best represented in the
      reserve and livestock streams. Present evidence suggests that the observed
      differences in the invertebrate composition in the agricultural streams were
      related with the impact of agrochemicals and that buffer strips represent a
      useful attenuation practice. Cattle breeding on natural pastures represented a
      land use with low impact on the invertebrate assemblages.

PMID- 29028498
TI  - Spinal segmental myoclonus resembling "belly dance" in a pregnant woman.

PMID- 29028499
TI  - Fasciculations in nerve and muscle disorders - A prospective study of muscle
      ultrasound compared to electromyography.
AB  - OBJECTIVES: We examined the clinical utility of muscle ultrasound (MUS) in
      detecting fasciculations in patients with nerve and muscle disorders (NMD) and
      investigated the impact on diagnostic sensitivity when combining electromyography
      (EMG) and MUS. METHODS: We included 58 consecutive patients suspected to have NMD
      and 38 healthy subjects (HS). Patients and HS underwent MUS in 14 skeletal and
      two bulbar muscles and the video recordings of the MUS were anonymised. Only
      patients underwent EMG. RESULTS: The follow-up diagnoses were: 15 Amyotrophic
      lateral sclerosis (ALS), 15 polyneuropathy, 14 patients had other diagnoses
      (disease-control group) and 14 patients had no pathological findings. MUS
      detected more muscles with fasciculations among ALS patients compared to all
      other groups. In ALS patients, the dominating pattern of fasciculations was
      continuous (45%). More proximal muscles showed fasciculations among ALS patients
      compared to all other patient groups. MUS was more sensitive than EMG in
      detecting fasciculations (58% vs. 48%). When combining the two methods, the
      sensitivity in detecting fasciculations increased to 65%. Fasciculations in nine
      muscles could predict the ALS diagnosis with high sensitivity and specificity.
      CONCLUSIONS: MUS is a sensitive tool in detecting fasciculations in patients with
      NMD and performs well compared to EMG in diagnosing ALS. SIGNIFICANCE: MUS may
      add valuable information in the clinic, especially in diagnosing ALS.

PMID- 29028500
TI  - Neural network topology in ADHD; evidence for maturational delay and default-mode
      network alterations.
AB  - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) has been associated
      with widespread brain abnormalities in white and grey matter, affecting not only
      local, but global functional networks as well. In this study, we explored these
      functional networks using source-reconstructed electroencephalography in ADHD and
      typically developing (TD) children. We expected evidence for maturational delay,
      with underlying abnormalities in the default mode network. METHODS:
      Electroencephalograms were recorded in ADHD (n=42) and TD (n=43) during rest, and
      functional connectivity (phase lag index) and graph (minimum spanning tree)
      parameters were derived. Dependent variables were global and local network
      metrics in theta, alpha and beta bands. RESULTS: We found evidence for a more
      centralized functional network in ADHD compared to TD children, with decreased
      diameter in the alpha band (etap2=0.06) and increased leaf fraction (etap2=0.11
      and 0.08) in the alpha and beta bands, with underlying abnormalities in hub
      regions of the brain, including default mode network. CONCLUSIONS: The finding of
      a more centralized network is in line with maturational delay models of ADHD and
      should be replicated in longitudinal designs. SIGNIFICANCE: This study
      contributes to the literature by combining high temporal and spatial resolution
      to construct EEG network topology, and associates maturational-delay and default
      mode interference hypotheses of ADHD.

PMID- 29028502
TI  - DOTA-tetrazine probes with modified linkers for tumor pretargeting.
AB  - INTRODUCTION: Pretargeted radioimmunoimaging and -therapy approaches building on
      the bioorthogonal inverse-electron-demand Diels-Alder (IEDDA) reaction between
      strained trans-cyclooctenes (TCO) and electron-deficient tetrazines (Tz) have
      yielded impressive results in recent years and have proven a vital alternative to
      biological pretargeting systems. After improvement of the TCO-antibody
      conjugates, we here report on our evaluation of a new series of radiolabeled Tz
      probes. METHODS: Four new Tz-probes were synthesized, radiolabeled with lutetium
      177, and characterized in vitro in terms of lipophilicity, reactivity, and
      stability in PBS and mouse serum. The in vivo biodistribution profile and tumor
      targeting potential of the probes were evaluated in LS174T tumor-bearing mice
      pretargeted with TCO-antibody conjugates using non-pretargeted mice as control.
      RESULTS: Radiolabeling of all probes proceeded in high yields providing the 177Lu
      labeled tetrazines in >95% radiochemical purity without any further purification.
      In mouse serum, half-lives of the probes varied between 8 and 13 h, with the
      exception of the most lipophilic probe, [177Lu]1b, with a serum half-life of less
      than 1 h. This probe also showed the fastest blood clearance (t1/2 = 5.4 min),
      more than 2-fold faster than PEG-linked probes [177Lu]3 and [177Lu]4, and even 3
      fold faster than the other small probes without the PEG-linker, [177Lu]1a and
      [177Lu]2. In the pretargeting experiments, tumor uptake of the lead probe
      [177Lu]4 (~6 %ID/g) was most closely approached by [177Lu]2, followed by [177Lu]3
      and [177Lu]1a. While all the smaller and more lipophilic probes suffered from
      increased liver uptake, the PEG-linked probe [177Lu]3 with its additional
      negative charge surprisingly showed the highest kidney uptake among all of the
      probes. CONCLUSION: The in vitro performance of some of the new tetrazine probes
      turned out to be comparable to the established lead probe [177Lu]Lu-DOTA-PEG11-Tz
      ([177Lu]4). However, tumor pretargeting studies in vivo showed lower tumor uptake
      and increased uptake in non-target organs.

PMID- 29028503
TI  - Unveiling the stimulatory effects of tartrazine on human and bovine serum albumin
      fibrillogenesis: Spectroscopic and microscopic study.
AB  - Amyloid fibrils are playing key role in the pathogenesis of various
      neurodegenerative diseases. Generally anionic molecules are known to induce
      amyloid fibril in several proteins. In this work, we have studied the effect of
      anionic food additive dye i.e., tartrazine (TZ) on the amyloid fibril formation
      of human serum albumins (HSA) and bovine serum albumin (BSA) at pHs7.4 and 3.5.
      We have employed various biophysical methods like, turbidity measurements,
      Rayleigh Light Scattering (RLS), Dynamic Light Scattering (DLS), intrinsic
      fluorescence, Congo red assay, far-UV CD, transmission electron microscopy (TEM)
      and atomic force microscopy (AFM) to decipher the mechanism of TZ-induce amyloid
      fibril formation in both the serum albumins at pHs7.4 and 3.5. The obtained
      results suggest that both the albumins forms amyloid-like aggregates in the
      presence of 1.0 to 15.0mM of TZ at pH3.5, but no amyloid fibril were seen at
      pH7.4. The possible cause of TZ-induced amyloid fibril formation is electrostatic
      and hydrophobic interaction because sulfate group of TZ may have interacted
      electrostatically with positively charged amino acids of the albumins at pH3.5
      and increased protein-protein and protein-TZ interactions leading to amyloid
      fibril formation. The TEM, RLS and DLS results are suggesting that BSA forms
      bigger size amyloids compared to HSA, may be due to high surface hydrophobicity
      of BSA.

PMID- 29028504
TI  - Research on differences between 2-(2'-pyridyl)benzimidazole and 2-(4'
      pyridyl)benzimidazole based on terahertz time-domain spectroscopy.
AB  - Due to the important pharmaceutical activities of benzimidazole derivatives, the
      differences between 2-(2'-pyridyl)benzimidazole and 2-(4'-pyridyl)benzimidazole
      were researched by terahertz time-domain spectroscopy and density functional
      theory systematically. Although the only difference between their molecular
      configurations is the different arrangement of nitrogen on pyridine ring, 2PBI
      and 4PBI have large differences in their experimental absorption spectra in the
      range of 0.2-2.5THz, such as the amount, amplitude and frequency position of
      absorption peaks. The validity of these results was confirmed by the theoretical
      results simulated using density functional theory. The possible reasons of these
      differences originate from the different dihedral angles between benzimidazole
      ring and pyridine ring and the different hydrogen-bonding interactions within
      crystal cell.

PMID- 29028501
TI  - Interindividual variability in response to continuous theta-burst stimulation in
      healthy adults.
AB  - OBJECTIVE: We used complete-linkage cluster analysis to identify healthy
      subpopulations with distinct responses to continuous theta-burst stimulation
      (cTBS). METHODS: 21 healthy adults (age+/-SD, 36.9+/-15.2years) underwent cTBS of
      left motor cortex. Natural log-transformed motor evoked potentials (LnMEPs) at 5
      50min post-cTBS (T5-T50) were calculated. RESULTS: Two clusters were found; Group
      1 (n=12) that showed significant MEP facilitation at T15, T20, and T50
      (p's<0.006), and Group 2 (n=9) that showed significant suppression at T5-T15
      (p's<0.022). LnMEPs at T10 and T40 were best predictors of, and together
      accounted for 80% of, cluster assignment. In an exploratory analysis, we examined
      the roles of brain-derived neurotrophic factor (BDNF) and apolipoprotein E (APOE)
      polymorphisms in the cTBS response. Val66Met participants showed greater
      facilitation at T10 than Val66Val participants (p=0.025). BDNF and cTBS intensity
      predicted 59% of interindividual variability in LnMEP at T10. APOE did not
      significantly affect LnMEPs at any time point (p's>0.32). CONCLUSIONS: Data
      driven cluster analysis can identify healthy subpopulations with distinct cTBS
      responses. T10 and T40 LnMEPs were best predictors of cluster assignment. T10
      LnMEP was influenced by BDNF polymorphism and cTBS intensity. SIGNIFICANCE:
      Healthy adults can be sorted into subpopulations with distinct cTBS responses
      that are influenced by genetics.

PMID- 29028505
TI  - Characterization and cysteine sensing performance of nanocomposites based on up
      conversion excitation host and rhodamine-derived probes.
AB  - Optical sensing for cysteine (Cys) recognition is an interesting topic due to Cys
      biological participation. In this paper, two rhodamine-based chemosensors were
      designed for Cys optical sensing. For chemosensor photostability improvement, up
      conversion nanocrystals were synthesized and used as excitation host. These
      nanocrystals were modified with a phase transfer reagent alpha-cyclodextrin
      (alpha-CD) to improve their compatibility with chemosensors. An efficient energy
      transfer from these nanocrystals to chemosensors under 980nm radiation was
      observed and confirmed by spectral match analysis, energy transfer radius
      calculation and emission decay lifetime comparison. A direct bonding mechanism
      between Cys and chemosensors with bonding stoichiometry of 1:1 was established by
      Job's plot experiment. Given the presence of Cys, chemosensor emission was
      increased, showing emission turn on effect. These two chemosensors showed good
      selectivity, improved photostability and linear sensing response towards Cys.

PMID- 29028507
TI  - Hydrogen bond docking preference in furans: OH?pi vs. OH?O.
AB  - The docking sites of hydrogen bonds in complexes formed between 2,2,2
      trifluoroethanol (TFE), furan (Fu), and 2-methyl furan (MF) have been
      investigated. Using density functional theory (DFT) calculations, gas phase and
      matrix isolation FTIR spectroscopies, the strengths of OH?O and OH?pi hydrogen
      bonds in the complexes were compared to find the docking preference. Calculations
      suggest that the hydrogen bond donor, TFE, is more likely to dock onto the oxygen
      atom of the aromatic furans ring, and consequently, the OH?O type hydrogen bond
      is relatively stronger than the OH?pi type. The FTIR spectrum in the OH
      stretching fundamental range obtained at room temperatures has been compared with
      that obtained at extremely low temperatures in the matrix. The fundamental and
      the red shifts of OH-stretching vibrations were observed in both FTIR spectra,
      confirming the formation of hydrogen bonded complexes. By assessing the ability
      of furan and MF to participate in the formation of OH?O hydrogen bond, the effect
      of ring methylation has been highlighted. From the calculated geometric and
      thermodynamic parameters as well as the frequency shift of the OH-stretching
      vibrations in complexes, TFE-MF is found to be more stable than TFE-Fu, which
      suggests that the strength of the OH?O hydrogen bond in TFE-MF originates from
      the high activity of the furan molecule caused by the methylation of the aromatic
      ring. The present study furthers the knowledge of docking preference in
      heteroaromatic molecules and is helpful to understand the nature of
      intermolecular interactions between hydrogen bond donors and acceptors, including
      both electron-deficient atoms and pi cloud.

PMID- 29028506
TI  - Sodium deoxycholate mediated enhanced solubilization and stability of hydrophobic
      drug Clozapine in pluronic micelles.
AB  - In this report, the solubilization behaviour of a hydrophobic drug Clozapine
      (CLZ) in micellar suspensions of pluronics having different hydrophilic
      lipophilic balance (HLB) ratios viz. P84, F127 and F108 in the absence and
      presence of bile salt sodium deoxycholate (SDC) has been studied. UV-Vis
      spectroscopy has been exploited to determine the solubilization capacity of the
      investigated micellar systems in terms of drug loading efficiency, average number
      of drug molecules solubilized per micelle (ns), partition coefficient (P) and
      standard free energy of solubilization (?G degrees ). The morphological and
      structural changes taking place in pluronics in different concentration regimes
      of SDC and with the addition of drug CLZ has been explored using dynamic light
      scattering (DLS) and small angle neutron scattering (SANS) measurements. The SANS
      results revealed that aggregation behaviour of pluronic-SDC mixed micelles gets
      improved in the presence of drug. The micropolarity measurements have been
      performed to shed light on the locus of solubilization of the drug in pure and
      mixed micellar systems. The compatibility between CLZ and drug carriers
      (pluronics and SDC) was confirmed using powder X-ray diffraction (PXRD) and
      Fourier transform infrared spectroscopy (FTIR) techniques. Among the investigated
      systems, P84-SDC mixed system was found to be highly efficient for CLZ loading.
      The long term stability data indicated that CLZ loaded P84-SDC mixed micellar
      formulation remained stable for 3months at room temperature. Further, it was
      revealed that the CLZ loaded P84-SDC mixed micelles are converted into CLZ loaded
      pure P84 micelles at 30-fold dilutions which remain stable up to 48-fold
      dilutions. The results from the present studies suggest that P84-SDC mixed
      micelles can serve as suitable delivery vehicles for hydrophobic drug CLZ.

PMID- 29028508
TI  - Jazz musicians reveal role of expectancy in human creativity.
AB  - Creativity has been defined as the ability to produce work that is novel, high in
      quality, and appropriate to an audience. While the nature of the creative process
      is under debate, many believe that creativity relies on real-time combinations of
      known neural and cognitive processes. One useful model of creativity comes from
      musical improvisation, such as in jazz, in which musicians spontaneously create
      novel sound sequences. Here we use jazz musicians to test the hypothesis that
      individuals with training in musical improvisation, which entails creative
      generation of musical ideas, might process expectancy differently. We compare
      jazz improvisers, non-improvising musicians, and non-musicians in the domain
      general task of divergent thinking, as well as the musical task of preference
      ratings for chord progressions that vary in expectation while EEGs were recorded.
      Behavioral results showed for the first time that jazz musicians preferred
      unexpected chord progressions. ERP results showed that unexpected stimuli
      elicited larger early and mid-latency ERP responses (ERAN and P3b), followed by
      smaller long-latency responses (Late Positivity Potential) in jazz musicians. The
      amplitudes of these ERP components were significantly correlated with behavioral
      measures of fluency and originality on the divergent thinking task. Together,
      results highlight the role of expectancy in creativity.

PMID- 29028509
TI  - Delayed-onset MRI findings in acute chorea related to anoxic brain injury.
AB  - Anoxic brain injury can manifest with various abnormal movements. We describe
      acute chorea in a young patient with anoxic brain injury due to chlordiazepoxide
      toxicity who had delayed radiographic lesions in bilateral globus pallidus.
      Although brain MRI 8days after the anoxic event was unremarkable, repeat brain
      MRI 15days after the event showed T2 hyperintensities and enhancement within the
      bilateral globus pallidi. It is possible that MRI brain findings of bilateral
      basal ganglia lesions may appear later than onset of chorea in anoxic brain
      injury. However, given the normal brain MRI in between, other etiologies cannot
      be excluded entirely.

PMID- 29028510
TI  - Comparison of virtual monochromatic series, iodine overlay maps, and single
      energy CT equivalent images in head and neck cancer conspicuity.
AB  - OBJECTIVE: To compare lesion conspicuity amongst DECT monochromatic series (40,
      45, 50keV), and single-energy CT (SECT) equivalent images in head and neck
      squamous cell carcinomas (HNSCC). METHODS: Two readers compared DECT images to
      70keV SECT equivalent series in 39 patients with HNSCC on lesion margin,
      enhancement, and overall conspicuity. RESULTS: The 45keV and 50keV images were
      significantly better (p-values <=0.001) than the SECT equivalent in lesion
      enhancement, margins, and overall conspicuity for both readers. Readers mostly
      preferred the 50keV monochromatic series. CONCLUSION: DECT can provide better
      lesion visualization than SECT in HNSCC.

PMID- 29028511
TI  - A pictorial review of diagnostic pitfalls of developmental anomalies and variants
      in pancreatic imaging.
AB  - Developmental anomalies and anatomic variants of the pancreas vary widely, and
      most of them are encountered incidentally during radiologic evaluation. However,
      some of these anomalies and variants are potentially pathologic and may cause
      various clinical presentations in childhood or adulthood. The early
      identification of these entities in various imaging modalities including
      ultrasound, computed tomography (CT), and magnetic resonance (MR) imaging would
      be valuable in making correct diagnoses and, in turn, preventing unnecessary
      additional procedures. In order to differentiate these entities, it is
      fundamental to understand the embryologic development and normal anatomical
      structure of the pancreas. In this article, we review the embryology and normal
      anatomy of the pancreas, and diagnostic pitfalls of developmental anomalies and
      anatomic variants in various pancreatic imaging modalities.

PMID- 29028512
TI  - The ectopic accessory parotid system: A new patient, studied through magnetic
      resonance imaging.
AB  - The ectopic accessory parotid system (EAPS) connotes an extra parotid tissue with
      its ductal outlet that is morphologically distinct from the main parotid gland
      and its drainage system. Clinically presenting as a saliva-draining cheek fistula
      near the oral commissure, this rare congenital anomaly is almost always
      associated with ipsilateral preauricular appendages and occasional mandibular
      hypoplasia, and is considered a variant of the oculo-auriculo-vertebral spectrum.
      This report discusses the embryology, clinical details, and management aspects in
      a new patient, highlighting the role of magnetic resonance imaging in, for the
      first time, tracking the ectopic salivary system, and establishing its
      independent existence.

PMID- 29028513
TI  - Occurrence and significance of morphologic changes in patients with metastatic
      triple negative breast cancer treated with Cabozantinib.
AB  - OBJECTIVE: To compare performance of RECIST1.1 and Choi criteria in assessment of
      patients with metastatic triple-negative breast cancer treated with cabozantinib.
      METHODS: Thirty patients with metastatic triple-negative breast cancer enrolled
      in phase 2 clinical trial received cabozantinib. Clinical benefit rates assessed
      by prospectively determined RECIST1.1 and retrospectively assessed Choi criteria
      were compared. RESULTS: Decreased tumor density (>=15%) at first follow-up was
      seen in 22/30(73%) patients. CBR was 40% (95%CI:23-59%) by RECIST1.1, and 73%
      (95%CI:54-88%) by Choi (NPV=100%, 95%CI:63-100%; PPV=55%, 95%CI:32-76%).
      CONCLUSIONS: Morphologic changes are seen in the majority of patients treated
      with cabozantinib, making Choi criteria valuable in response assessment.

PMID- 29028514
TI  - Solitary fibrous tumor in the abdomen and pelvis: A case series with radiological
      findings and treatment recommendations.
AB  - This study presents the radiological findings of seven cases of solitary fibrous
      tumor (SFT) in the abdomen and pelvis. A retrospective search of the pathology
      database at our institution was performed to identify cases of SFT in the abdomen
      and pelvis. After identifying seven cases, cross-sectional imaging was reviewed
      and characterized. We conclude that SFTs in the abdomen and pelvis should be
      considered with well-defined, circular, hypervascular masses. Pelvic SFTs should
      be considered with homogenous, avidly enhancing masses. Embolization of feeding
      arteries can allow safe surgical resection or biopsy, but embolization appears to
      not offer a definitive therapy.

PMID- 29028515
TI  - Post-biopsy MRI changes in the size and enhancement of intramuscular myxomas: A
      report of two cases.
AB  - Intramuscular myxomas are benign soft-tissue tumors, characterized by bland
      spindle-shaped cells and fibroblasts within an abundant mucoid matrix on
      histologic examination. Classically, these are slowly enlarging masses which may
      occasionally cause pain, paresthesia, and muscle weakness secondary to mass
      effect. We present an interesting phenomenon of two histologically confirmed
      cases of intramuscular myxomas that exhibited size and enhancement changes on
      follow-up imaging after image-guided biopsy. To our knowledge, this is the first
      report to describe size and enhancement changes of intramuscular myxomas after
      biopsy.

PMID- 29028516
TI  - Pravastatin to treat and prevent preeclampsia. Preclinical and clinical studies.
AB  - Pre-eclampsia is a disease of pregnancy affecting 5%-8% of all pregnancies and a
      leading cause of maternal and fetal mortality. Despite improvements in the
      diagnosis, there is no effective method for prevention and treatment. While
      studies in women are of critical importance, investigation of pathological
      mechanisms in pregnant women is necessarily limited, and the ability to establish
      cause and effect relationships, difficult. Mouse models have been instrumental in
      defining pathogenic mechanisms in preeclampsia and in the identification of
      pravastatin as a potential treatment to prevent pregnancy complications
      associated with placental dysfunction. Numerous epidemiological studies provided
      robust evidence demonstrating that pravastatin exposure during pregnancy does not
      affect fetal development. In addition, pravastatin is hydrophilic and has a
      limited passage through the placenta, diminishing any safety concerns. Several
      pilot studies suggest that pravastatin may be a good option to prevent and treat
      preeclampsia in women. While these studies are promising, the effectiveness of
      pravastatin to treat preeclampsia needs to be confirmed by randomized clinical
      trials.

PMID- 29028517
TI  - Effect of carbamazepine and oxcarbazepine on serum neuron-specific enolase in
      focal seizures: A randomized controlled trial.
AB  - Neuron-specific enolase (NSE) is the most investigated biomarker in the context
      of epilepsy and brain damage. The present study was conducted to investigate the
      change in serum NSE in patients with focal seizure and the effect of
      carbamazepine and oxcarbazepine on serum NSE. The present study is a randomized,
      open-label, parallel design clinical trial (ClinicalTrials.gov Identifier:
      NCT02705768) conducted on 60 patients of focal seizure. After recruitment,
      detailed history, clinical evaluations including Chalfont-National Hospital
      seizure severity scale (NHS3), Quality of Life in Epilepsy Inventory (QOLIE-31)
      and serum NSE estimation were done at baseline. Thirty healthy volunteers were
      recruited for a baseline evaluation of serum NSE. After randomization, one group
      received tablet oxcarbazepine and another group received tablet carbamazepine. At
      4 weeks follow-up, all the parameter were reassessed. Serum NSE level was found
      to be significantly increased in patients with focal seizure in comparison to
      healthy volunteers. In both drug groups, serum NSE decreased significantly but
      the reduction in carbamazepine group (1.43; 95%CI: 0.18-2.67; p=0.025) was
      significantly higher than oxcarbazepine group.NHS3 score, score in all seven
      domains of QOLIE-31 and final QOLIE-31 score improved significantly in both the
      groups. In conclusion, serum NSE increases in the patients with focal seizure
      within 48h of a seizure episode. Therapy with carbamazepine and oxcarbazepine can
      decrease serum NSE level but the reduction is significantly higher with
      carbamazepine. Therapy with both the drugs can decrease the severity of epilepsy
      and improve the quality of life but adverse events were more with carbamazepine.

PMID- 29028518
TI  - Absence of distracting information explains the redundant signals effect for a
      centrally presented categorization task.
AB  - The redundant signals effect, a speed-up in response times with multiple targets
      compared to a single target in one display, is well-documented, with some
      evidence suggesting that it can occur even in conceptual processing when targets
      are presented bilaterally. The current study was designed to determine whether or
      not category-based redundant signals can speed up processing even without
      bilateral presentation. Toward that end, participants performed a go/no-go visual
      task in which they responded only to members of the target category (i.e., they
      responded only to numbers and did not respond to letters). Numbers and letters
      were presented along an imaginary vertical line in the center of the visual
      field. When the single signal trials contained a nontarget letter (Experiment 1),
      there was a significant redundant signals effect. The effect was not significant
      when the single-signal trials did not contain a nontarget letter (Experiments 2
      and 3). The results indicate that, when targets are defined categorically and not
      presented bilaterally, the redundant signals effect may be an effect of reducing
      the presence of information that draws attention away from the target. This
      suggests that redundant signals may not speed up conceptual processing when
      interhemispheric presentation is not available.

PMID- 29028519
TI  - TEM observation on phase separation and interfaces of laser surface alloyed high
      entropy alloy coating.
AB  - Phase separation is a common phenomenon in traditional alloys. Under the
      condition of appropriate undercooling, the segregation phenomenon can be also
      found in blue-chip high-entropy alloys (HEAs). In this work, the phase separation
      behavior and interfacial investigation of laser surface alloyed HEA coating with
      high content Ti were studied principally by transmission electron microscopy. The
      results show that crystal structure and elementary composition on both sides of
      the interface of coating/substrate are quite different, and the interfaces
      between different phases are incoherent or semi-coherent boundarys, resolved by
      high resolution transmission electron microscopy. In the interface of (Co, Ni)Ti2
      phase/beta-Ti phase, there is angle of 80 degrees  between BCC<100> and FCC<201>.
      An interesting 'island' structure, that beta-Ti phases are embraced by (Co,
      Ni)Ti2 compounds in the BCC matrix, was observed definitely, which is attributed
      to the combined action of Ti segregation and inter-attraction of Ti and other
      elements.

PMID- 29028521
TI  - Age at menarche and depressive symptoms in older Southern Chinese women: A
      Mendelian randomization study in the Guangzhou Biobank Cohort Study.
AB  - To clarify the causal role of age at menarche in depressive symptoms we conducted
      a Mendelian randomization study using a large Southern Chinese cohort (n =
      12,233). A genetic allele score was derived using stepwise regression with cross
      validation. Older age at menarche was not associated with geriatric depression
      scale score. Our findings suggest that higher rates of depression in women are
      likely attributable to other factors which require investigation.

PMID- 29028520
TI  - Socioeconomic status and childhood autism: A population-based study in China.
AB  - There is limited evidence on the association between socioeconomic status (SES)
      and autism in developing nations. The aim of this study was to examine this
      association among children aged 0-17 years in China. We obtained data from the
      Second National Sample Survey on Disability, and selected 616,940 children for
      analysis. Autism was ascertained according to the International Statistical
      Classification of Diseases, Tenth Revision. Multiple logistic regressions
      allowing for weights showed that children in middle-income and high-income
      families were less likely than their low-income peers to have autism, with an
      odds ratio of 0.60 (95%CI: 0.39, 0.93) and 0.44 (95%CI: 0.27, 0.72),
      respectively. Children in middle-education families had 63% (95%CI: 41%, 95%)
      odds of autism relative to their counterparts in low-education families.
      Stratified analyses found that all observed associations were only in male
      children, not in female children. In conclusion, children in families with
      socioeconomic disadvantage, in the form of lower family income and education, had
      greater risk of childhood autism.

PMID- 29028522
TI  - An examination of sex differences in neurocognition and social cognition in first
      episode psychosis.
AB  - Due to the dearth and conflicting findings of previous research, it is unclear
      whether males and females with first-episode psychosis (FEP) differ in their
      neurocognitive and social cognitive abilities. The aims of the current study were
      to investigate whether: (i) there are sex differences in neurocognition and
      social cognition among young people with FEP; and (ii) they resemble those
      observed in age-matched healthy controls. The current study involved secondary
      analysis of data from a previous study in which a large neurocognitive and social
      cognitive battery was administered to 146 individuals with FEP and 46 healthy
      controls aged 15-25 years. Seven two-way between-groups multivariate analysis of
      variances revealed that FEP participants were impaired relative to controls on
      all cognitive domains. Only one main effect of sex was found with males,
      regardless of group, outperforming females on verbal comprehension. A significant
      interaction effect was found for information processing speed with FEP females
      outperforming FEP males on the Symbol Digit Modalities Test; however, post-hoc
      analysis of the mean difference was not significant. Despite few sex differences,
      the current study highlights that cognitive impairment is a key feature of FEP
      that should be a treatment target in early intervention.

PMID- 29028523
TI  - The interplay between trait anxiety, cognitive biases and attentional control in
      healthy individuals with psychotic-like experiences.
AB  - Although both anxiety and cognitive biases contribute to psychosis, it is still
      unclear whether these factors interact in their influence on psychotic symptoms.
      The aim of the study was to examine the interactions between trait anxiety,
      cognitive biases and delusion-like experiences (PLEs) in a non-clinical sample;
      the moderational role of attentional control on this relationship was also
      considered in the study. Two subgroups of participants, 92 individuals (M=24.76;
      SD=6.33) with heightened (HA) trait anxiety and 78 individuals (M=23.09; SD=5.66)
      with lowered (LA) trait anxiety took part in the study. Anxiety, cognitive biases
      and attentional control were measured using self-report questionnaires.
      Regression analyses and moderation analyses were performed. External attribution
      bias predicted psychotic-like experiences in both groups, whereas attention to
      threat bias and belief inflexibility predicted PLEs within LA group. Further
      moderation analyses revealed that in LA group attention to threat bias increases
      PLEs only among individuals with a high and moderate ability to focus attention.
      The results indicated that trait anxiety is an important factor influencing the
      relationship between cognitive biases and PLEs, and that the ability to
      voluntarily focus attention is a significant moderator of the linkage between
      attention to threat bias and delusion-like experiences among low-anxious healthy
      individuals.

PMID- 29028524
TI  - Sleep health assessment: A scale validation.
AB  - Sleep health is a new and important concept. Considering the need to expand the
      research on sleep from the health perspective, this research proposes to validate
      a Sleep Health Scale (SHS) for use with the Portuguese adult population. A sample
      of 540 community-dwelling adults aged 18-90 years old was included. The SHS
      scores ranged from 0 to 30 with a mean of 19.09 (SD +/- 6.49). The distribution
      indicated that all socio demographic variables (age, gender, and literacy)
      influenced sleep health. Exploratory factor analysis (EFA) demonstrated one
      factor for this measurement model with poor indices (Chi-square (df) = 55.02(9),
      p < 0.001). Confirmatory factor analysis (CFA) was performed on the single factor
      and showed a well-adjusted model except for question 5 (Chi-square (df) =
      11.443(4), p = 0.022; RMSEA = 0.084; CFI=0.99; GFI = 0.98; AGFI = 0.94), the
      convergent validity (AVE = 0.55) and reliability values (alpha = 0.85 /CR = 0.86)
      were good. In conclusion, the Sleep Health Scale (SHS) is valid and reliable for
      the assessment of the several sleep health indicators of Portuguese adults. An
      investigation on the relationship between sleep health and well-being in
      promoting quality of life with this scale is recommended for future research.

PMID- 29028525
TI  - Risk taking and adult attention deficit/hyperactivity disorder: A gap between
      real life behavior and experimental decision making.
AB  - Adults with attention deficit/hyperactivity disorder (ADHD) are prone to
      suboptimal decision making and risk taking. The aim of this study was to test
      performance on a theoretically-based probabilistic decision making task in well
      characterized adults with and without ADHD, and examine the relation between
      experimental risk taking and history of real-life risk-taking behavior, defined
      as cigarette, alcohol, and street drug use. University students with and without
      ADHD completed a modified version of the Cambridge Gambling Test, in which they
      had to choose between alternatives varied by level of risk, and reported their
      history of substance use. Both groups showed similar patterns of risk taking on
      the experimental decision making task, suggesting that ADHD is not linked to low
      sensitivity to risk. Past and present substance use was more prevalent in adults
      with ADHD. These finding question the validity of experimental probabilistic
      decision making task as a valid model for ADHD-related risk-taking behavior.

PMID- 29028526
TI  - Semantic coherence in psychometric schizotypy: An investigation using Latent
      Semantic Analysis.
AB  - Technological advancements have led to the development of automated methods for
      assessing semantic coherence in psychiatric populations. Latent Semantic Analysis
      (LSA) is an automated method that has been used to quantify semantic coherence in
      schizophrenia-spectrum disorders. The current study examined whether: 1) Semantic
      coherence reductions extended to psychometrically-defined schizotypy and 2)
      Greater cognitive load further reduces semantic coherence. LSA was applied to
      responses generated during category fluency tasks in baseline and cognitive load
      conditions. Significant differences between schizotypy and non-schizotypy groups
      were not observed. Findings suggest that semantic coherence may be relatively
      preserved at this point on the schizophrenia-spectrum.

PMID- 29028527
TI  - Identification and optimization of novel 6-acylamino-2-aminoquinolines as potent
      Hsp90 C-terminal inhibitors.
AB  - In order to discover novel Hsp90 inhibitors targeting the C-terminal ATP binding
      pocket, a novobiocin derivative based ROCS model was constructed for virtual
      screening. Compound 13 was identified as the lead compound and then systematical
      structure activity relationship (SAR) study was conducted. These efforts led to
      compound 69, which exhibited potent anti-proliferative activities against MCF7
      and SKBr3 breast cancer cell lines. In 4T1 mice breast cancer models, 69
      exhibited potent tumor growth inhibition and anti-metastasis effect. Compound 69
      as a potent antitumor agent targeting the Hsp90 C-terminal is worthy of further
      pre-clinical study.

PMID- 29028528
TI  - Inhibitors of Yellow Fever Virus replication based on 1,3,5-triphenyl-4,5
      dihydropyrazole scaffold: Design, synthesis and antiviral evaluation.
AB  - By the antiviral screening of an in house library of pyrazoline compounds, 4-(3
      (4-phenoxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide (5a)
      was identified as a promising hit compound for the development of anti- Yellow
      Fever Virus (YFV) agents. Structural optimization studies were focused on the
      development of 5a analogues which retain the potency as YFV inhibitors and show a
      reduced cytotoxicity. The synthesized 1-3,5-triphenyl-pyrazolines (4a-j, 5a-j, 6a
      j) were evaluated in cell based assays for cytotoxicity and antiviral activity
      against representative viruses of two of the three genera of the Flaviviridae
      family, i.e.: Pestivirus (BVDV) and Flavivirus (YFV). These compounds were also
      tested against a large panel of different pathogenic RNA and DNA viruses. Most of
      the new 1-3,5-triphenyl-pyrazolines (4a-j, 5a-j, 6a-j) exhibited a specific
      activity against YFV, showing EC50 values in the low micromolar range with almost
      a 10-fold improvement in potency compared to the reference inhibitor 6
      azauridine. However, the selectivity indexes of the unsubstituted (4a-j) and the
      phenoxy (5a-j) analogues were generally modest due to the pronounced cytotoxicity
      against BHK-21 cells. Otherwise, the benzyloxy derivatives (6a-j) generally
      coupled high potency and selectivity. On the basis of both anti-YFV activity and
      selectivity index, pyrazolines 6a and 6b were chosen for time of addition
      experiments. The selected pyrazolines and the reference inhibitor 6-azauridine
      displayed maximal inhibition when added in the pretreatment or during the
      infection.

PMID- 29028529
TI  - Design, synthesis and immunological evaluation of novel amphiphilic desmuramyl
      peptides.
AB  - Muramyl dipeptide (MDP) - an essential bacterial cell wall component - is
      recognized by our immune system as pathogen-associated molecular pattern (PAMP)
      which results in immune responses with adverse toxic effects. In order to harness
      the beneficial properties from the pro-inflammatory characteristics of the
      bacterial cell wall motif, MDP was strategically re-designed while conserving the
      L-D configurations of the dipeptide moiety. The muramic acid was replaced with a
      hydrophilic arene and lipophilic chain was introduced at peptide end to give the
      amphiphilic desmuramyl peptides (DMPs). The novel DMPs were found to modulate the
      immune response by amplifying the LPS-induced surface glycoprotein (ICAM-1)
      expression in THP-1 cells without showing significant toxicity. Furthermore,
      these compounds were able to trigger the secretion of higher levels of pro
      inflammatory cytokine (TNF-alpha) than the well-studied NOD2 agonist, Murabutide.

PMID- 29028530
TI  - A pentanoic acid derivative targeting matrix metalloproteinase-2 (MMP-2) induces
      apoptosis in a chronic myeloid leukemia cell line.
AB  - Depending on our previous observations, some compounds of pentanoic acid were
      designed and synthesized. Characterization of the synthesized compounds was done
      by mass, NMR and IR spectroscopy as well as elemental analysis. Among the
      synthesized molecules, (2S)-5-oxo-2-[(nitrobenzene-4-yl sulfonyl) amino]-5
      (pentylamino) pentanoic acid (Cpd 11) was found as a lead and potent inhibitor of
      matrix metalloproteinase-2 (MMP-2). Molecular modeling and enzyme inhibition
      studies were done to confirm the interaction or inhibitory potential of this
      compound. Thereafter, the biological screening was done through cytotoxicity,
      anti-invasion and apoptosis-related assays. Docking analysis revealed that Cpd 11
      interacted with the target molecule MMP-2 and with MMP-9. However, enzyme
      inhibition assay showed 3-fold MMP-2 inhibition compared to MMP-9. Cytotoxicity
      assay showed the inhibitory potential of Cpd 11 against K562 cell line having
      IC50 value of 17.9 +/- 0.01 MUM after 48 h of incubation. The cell death was
      apoptotic in nature as revealed from the annexin V and sub-G1 cell cycle arrest
      assay. Besides this, Cpd 11 also exhibited dose dependent anti-invasive activity
      into K562 cell line. On the other hand, flow cytometry and western blot data
      revealed Cpd 11 induced downregulation of MMP-2 in K562 cell line after 48 h of
      incubation that might be linked with the anti-invasive and apoptotic activity
      furthermore. Therefore, the overall results validated each method and make this
      molecule as a potent MMP-2 inhibitor that blocked the invasion and could bring
      apoptosis at later stages in K562 cells sparing the normal ones.

PMID- 29028531
TI  - Synthesis and biological evaluation of novel non-racemic indole-containing
      allocolchicinoids.
AB  - Two novel indole-containing allocolchicinoids were prepared from naturally
      occurring colchicine exploiting the Curtius rearrangement and tandem Sonogashira
      coupling/Pd-catalyzed cyclization as the key transformations. Their cytotoxic
      properties, apoptosis-inducing activity, tubulin assembly inhibition and short
      time cytotoxic effects were investigated. Compound 7 demonstrated the most
      pronounced anti-cancer activity: IC50 < 1 nM, cell cycle arrest in the G2/M
      phase, 25% apoptosis induction, as well as lower destructive short-time effects
      on HT-29 cell line in comparison with colchicine. Docking studies for prepared
      indole-derived allocolchicine analogues were carried out.

PMID- 29028532
TI  - New dimeric cGMP analogues reduce proliferation in three colon cancer cell lines.
AB  - Activation of the cGMP-dependent protein kinase G (PKG) can inhibit growth and/or
      induce apoptosis in colon cancer. In this study we evaluated the effects on cell
      viability, cell death and proliferation of novel dimeric cGMP analogues, compared
      to a monomeric compound. Three colon cancer cell lines, which only express
      isoform 2 of PKG, were treated with these novel cGMP analogues and responded with
      increased PKG activity. cGMP analogues reduced cell viability in the three cell
      lines and this was due to a cytostatic rather than cytotoxic effect. These
      findings suggest that activation of PKG2 can be a therapeutic target in the
      treatment of colon cancer and, most importantly, that dimeric cGMP analogues can
      further improve the beneficial effects previously observed with monomeric cGMP
      analogues.

PMID- 29028533
TI  - Triclosan-caffeic acid hybrids: Synthesis, leishmanicidal, trypanocidal and
      cytotoxic activities.
AB  - The synthesis, cytotoxicity, anti-leishmanial and anti-trypanosomal activities of
      twelve triclosan-caffeic acid hybrids are described herein. The structure of the
      synthesized products was elucidated by a combination of spectrometric analyses.
      The synthesized compounds were evaluated against amastigotes forms of L. (V)
      panamensis, which is the most prevalent Leishmania species in Colombia, and
      against Trypanosoma cruzi, which is the pathogenic species to humans.
      Cytotoxicity was evaluated against human U-937 macrophages. Eight compounds were
      active against L. (V) panamensis (18-23, 26 and 30) and eight of them against T.
      cruzi (19-22, 24 and 28-30) with EC50 values lower than 40 MUM. Compounds 19-22,
      24 and 28-30 showed higher activities than benznidazole (BNZ). Esters 19 and 21
      were the most active compounds for both L. (V) panamensis and T. cruzi with 3.82
      and 11.65 MUM and 8.25 and 8.69 MUM, respectively. Compounds 19-22, 24 and 28-30
      showed higher activities than benznidazole (BNZ). Most of the compounds showed
      antiprotozoal activity and with exception of 18, 26 and 28, the remaining
      compounds were toxic for mammalian cells, yet they have potential to be
      considered as candidates for anti-trypanosomal and anti-leishmanial drug
      development. The activity is dependent on the length of the alkyl linker with
      compound 19, bearing a four-carbon alkyl chain, the most performing hybrid. In
      general, hydroxyl groups increase both activity and cytotoxicity and the presence
      of the double bond in the side chain is not decisive for cytotoxicity and anti
      protozoal activity.

PMID- 29028534
TI  - Discovery of Benzo[g]quinazolin benzenesulfonamide derivatives as dual EGFR/HER2
      inhibitors.
AB  - An array of some new N-(substituted)-2-((4-oxo-3-(4-sulfamoylphenyl)-3,4
      dihydrobenzo[g]quinazolin-2-yl)thio)acetamide 5-19 were synthesized from the
      starting compound 4-(2-mercapto-4-oxobenzo[g]quinazolin-3(4H)
      yl)benzenesulfonamide 4, to be assessed for their cytotoxic activity against A549
      lung cancer cell line and to determine their inhibitory effect on EGFR tyrosine
      kinase enzyme. Compounds 5-19 showed high activity towards A549 cell line with
      IC50 values of 0.12-8.70 MUM. Compounds 6, 12 and 18 were the most potent in this
      series. These compounds were further screened as dual inhibitors for EGFR/HER2
      enzymes in comparison with erlotinib and were found to possess very potent
      activity. Compound 12 showed the highest activity with IC50 values of 0.06 MUM
      and 0.30 MUM towards EGFR and HER2, respectively. Accordingly, the apoptotic
      effect of the most potent compounds 6, 12 and 18 was investigated and showed a
      marked increase in the level of caspases-3 by 6, 9 and 8 folds, respectively,
      compared to the control cells. Moreover, Molecular modeling was performed inside
      the active site of EGFR, keeping in mind their binding possibilities, bond
      lengths, angles and energy scores. It was found that the most active compounds
      demonstrated the best binding scores in the active site of EGFR, which may
      clarify their high inhibition profile.

PMID- 29028535
TI  - Baicalin and its metabolites suppresses gluconeogenesis through activation of
      AMPK or AKT in insulin resistant HepG-2 cells.
AB  - Scutellaria baicalensis Georgi (S. baicalensis), as a traditional Chinese herbal
      medicine, is an important component of several famous Chinese medicinal formulas
      for treating patients with diabetes mellitus. Baicalin (BG), a main bioactive
      component of S. baicalensis, has been reported to have antidiabetic effects.
      However, pharmacokinetic studies have indicated that BG has poor oral
      bioavailability. Therefore, it is hard to explain the pharmacological effects of
      BG in vivo. Interestingly, several reports show that BG is extensively
      metabolized in rats and humans. Therefore, we speculate that the BG metabolites
      might be responsible for the pharmacological effects. In this study, BG and its
      three metabolites (M1-M3) were examined their effects on glucose consumption in
      insulin resistant HepG-2 cells with a commercial glucose assay kit. Real-time PCR
      and western blot assay were used to confirm genes and proteins of interest,
      respectively. The results demonstrate that BG and its metabolites (except for M3)
      enhanced the glucose consumption which might be associated with inhibiting the
      expression of the key gluconeogenic genes, including glucose-6-phosphatase
      (G6Pase), phosphoenolypyruvate carboxykinase (PEPCK) and glucose transporter 2
      (GLUT2). Further study found that BG and M1 could suppress hepatic
      gluconeogenesis via activation of the AMPK pathway, while M2 could suppress
      hepatic gluconeogenesis via activation of the PI3K/AKT signaling pathway. Taken
      together, our findings suggest that both BG and its metabolites have
      antihyperglycemic activities, and might be the active forms of oral doses of BG
      in vivo.

PMID- 29028536
TI  - Attitudes mediate the intergenerational transmission of corporal punishment in
      China.
AB  - This research aimed to examine the intergenerational transmission of corporal
      punishment and the role of parents' attitudes toward corporal punishment in the
      transmission processes in Chinese societies. Based on social-cognitive theory, it
      was hypothesized that parents' attitudes toward corporal punishment would mediate
      the transmission of corporal punishment. Seven hundred and eighty-five fathers
      and eight hundred and eleven mothers with elementary school-age children (data
      collected in winter 2009) were recruited through convenience sampling techniques.
      The Chinese version of Parent-Child Conflict Tactics Scale (CTSPC) and Attitude
      toward Physical Punishment Scale (ATPP) were used as the main assessment tools to
      measure parents' corporal punishment experiences in childhood, current use of
      corporal punishment and attitudes toward corporal punishment. Findings revealed
      that the strength of intergenerational transmission of corporal punishment was
      strong and parents' attitudes toward corporal punishment played a mediating role
      in the continuity of corporal punishment for both fathers and mothers in China.
      The findings highlighted the role of attitudes in the intergenerational
      transmission of corporal punishment within the Chinese cultural context and also
      suggested the need for intervention programs to focus on modification of
      maladaptive attitudes toward what is appropriate and effective discipline.

PMID- 29028537
TI  - Facile surface-engineered polymeric absorbents for simultaneous adsorption and
      degradation of organic wastes.
AB  - Polymeric absorbents were surface-engineered with photocatalysts for simultaneous
      adsorption and degradation of organic wastes in water using a facile Pickering
      emulsion polymerization method. This facile strategy not only overcome the low
      light energy utilization of traditional photocatalysts-polymer nanocomposites due
      to the core-shell structure, but also could convenient control the microstructure
      of the photocatalysts owing to the separated preparation procedure when compared
      to the direct growth method. Firstly, binary bismuth oxyhalide composed as
      BiOI0.5Cl0.5 was chosen to engineered polymeric absorbents due to its higher
      photodegradation efficiency especially. After the emulsification and
      polymerization process, BiOI0.5Cl0.5 acting as the stabilizer would be fixed on
      the surface of the functional polymeric absorbents to form PA@BiOI0.5Cl0.5. Batch
      experiments were lunched using phenol as the test substance, the results shown
      that PA@BiOI0.5Cl0.5 could remove phenol completely within a short time and could
      be reused without any treatments with a simultaneous adsorption and degradation
      process. Furthermore, polymeric absorbents were engineered with commercial TiO2
      to prove the generality of this strategy.

PMID- 29028538
TI  - Nitric oxide induces rice tolerance to excessive nickel by regulating nickel
      uptake, reactive oxygen species detoxification and defense-related gene
      expression.
AB  - Soil contamination with nickel (Ni) is a persistent threat to crop production
      worldwide. The present study examined the putative roles of nitric oxide (NO) in
      improving Ni-tolerance in rice. Our findings showed that application of exogenous
      sodium nitroprusside (SNP), a NO donor, significantly improved the growth
      performance of rice seedlings when grown under excessive Ni. The enhanced Ni
      tolerance of rice prompted by SNP could be ascribed to its ability to regulate Ni
      uptake, decrease Ni-induced oxidative stress as evidenced by reduced levels of
      hydrogen peroxide, malondialdehyde, and electrolyte leakage in Ni-stressed
      plants. The positive roles of NO against Ni-toxicity also reflected through its
      protective effects on photosynthetic pigments, soluble proteins and proline. SNP
      also boosted antioxidant capacity in Ni-stressed plants by maintaining increased
      levels of ascorbate, enhanced activities of ROS-detoxifying enzymes, particularly
      peroxidase (POD) and catalase (CAT) in both roots and shoots compared with Ni
      stressed alone plants. Moreover, SNP treatment also upregulated the transcript
      levels of CAT, POD, ascorbate peroxidase, glutathione reductase and superoxide
      dismutase genes in shoots under Ni-stress. Using different sulfide compounds and
      NO scavenger cPTIO, we also provided evidence that NO, rather than other
      byproducts of SNP, contributed to the improved performance of rice seedlings
      under Ni-stress. Collectively, our results conclude that exogenous SNP-mediated
      modulation of endogenous NO enhanced rice tolerance to Ni-stress by restricting
      Ni accumulation, maintaining photosynthetic performance and reducing oxidative
      damage through improved antioxidant system, thereby suggesting NO as an effective
      stress regulator in mitigating Ni-toxicity in economically important rice, and
      perhaps in other crop plants.

PMID- 29028539
TI  - Electrospun polycaprolactam-manganese oxide fiber for headspace-solid phase
      microextraction of phthalate esters in water samples.
AB  - The nanofibrous polycaprolactam (polyamide 6 (PA6)) incorporated with manganese
      oxide (MnO) nanoparticles was fabricated by electrospinning and used as a new
      fiber coating for headspace-solid phase microextraction (HS-SPME) of the selected
      phthalate esters (PEs) in water samples prior to GC-MUECD. The adsorbent was
      fully characterized using scanning electron microscopy (SEM), Fourier transform
      infrared (FT-IR) spectroscopy and thermogravimetric analysis (TGA). The main
      parameters that affect the HS-SPME efficiency such as extraction temperature,
      ionic strength, extraction and desorption times were investigated. The analytical
      figures of merit were obtained under the optimized conditions as follows: linear
      dynamic range (LDR), 0.500-5.00 * 102 ng mL-1; relative standard deviations
      (RSDs, n = 3), 1.86-10.9%; limits of detection (LODs), 0.0400-0.193 ng mL-1. The
      method was applied for determination of the target analytes in river water,
      bottled water, mineral water and soda samples and the relative recoveries were
      obtained between 90.3 and 107%.

PMID- 29028540
TI  - Endo-lysosomal dysfunction: a converging mechanism in neurodegenerative diseases.
AB  - Endo-lysosomal pathways are essential in maintaining protein homeostasis in the
      cell. Numerous genes in the endo-lysosomal pathways have been found to associate
      with neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's
      disease (PD), and frontotemporal dementia (FTD). Mutations of these genes lead to
      dysfunction in multiple steps of the endo-lysosomal network: autophagy, endocytic
      trafficking and lysosomal degradation, resulting in accumulation of pathogenic
      proteins. Although the exact pathogenic mechanism varies for different disease
      associated genes, dysfunction of the endo-lysosomal pathways represents a
      converging mechanism shared by these diseases. Therefore, strategies that correct
      or compensate for endo-lysosomal dysfunction may be promising therapeutic
      approaches to treat neurodegenerative diseases.

PMID- 29028542
TI  - Spectral diffusion and dynamic nuclear polarization: Beyond the high temperature
      approximation.
AB  - Dynamic Nuclear Polarization (DNP) has proven itself most powerful for the
      orientation of nuclear spins in polarized targets and for hyperpolarization in
      magnetic resonance imaging (MRI). Unfortunately, the theoretical description of
      some of the processes involved in DNP invokes the high temperature approximation,
      in which Boltzmann factors are expanded up to first order, while the high
      electron and nuclear spin polarization required for many applications do not
      justify such an approximation. A previous article extended the description of one
      of the mechanisms of DNP-thermal mixing-beyond the high temperature approximation
      (Wenckebach, 2017). But that extension is still limited: it assumes that fast
      spectral diffusion creates a local equilibrium in the electron spin system.
      Provotorov's theory of cross-relaxation enables a consistent further extension to
      slower spectral diffusion, but also invokes the high temperature approximation.
      The present article extends the theory of cross-relaxation to low temperature and
      applies it to spectral diffusion in glasses doped with paramagnetic centres with
      anisotropic g-tensors. The formalism is used to describe DNP via the mechanism of
      the cross effect. In the limit of fast spectral diffusion the results converge to
      those obtained in Wenckebach (2017) for thermal mixing. In the limit of slow
      spectral diffusion a hole is burnt in the electron spin resonance (ESR) signal,
      just as predicted by more simple models. The theory is applied to DNP of proton
      and 13C spins in samples doped with the radical TEMPO.

PMID- 29028541
TI  - Tuning the structure of aminoferrocene-based anticancer prodrugs to prevent their
      aggregation in aqueous solution.
AB  - Aminoferrocene-based prodrugs are activated in cancer cells by reactive oxygen
      species (ROS). They were shown to exhibit high cytotoxicity towards a variety of
      cancer cell lines and primary cancer cells, but remain not toxic towards non
      malignant cells. However, these prodrugs have rather high lipophilicity leading
      to relatively low water solubility. In particular, an n-octanol/water partition
      coefficient for the best aminoferrocene-based prodrug (2) was found to be 4.51+/
      0.03. Though the approaches for decreasing lipophilicity are straightforward and
      include the addition of polar residues to the drug structure, these modifications
      also lead to dramatic decrease of cell permeability and, correspondingly, lower
      the activity of the drug. Therefore, a delicate balance of polar and unpolar
      groups should be found to reduce lipophilicity without compromising the useful
      drug properties. In this study we optimized an N-alkyl substituent, which is a
      key element responsible for the stabilization of the aminoferrocene drug released
      in cancer cells from prodrug 2. We found that an N-propargyl residue is an
      optimal replacement for the N-benzyl fragment. In particular, such a substitution
      (prodrug 7a) leads to reduction of prodrug lipophilicity down to logP=3.78+/
      0.05, improvement of its water solubility, decrease of its propensity towards
      aggregation and dramatic increase of its ROS-generating properties. Finally, we
      demonstrated that the optimized prodrug strongly suppresses growth of Guerin's
      carcinoma (T8) in vivo at the dose of 30mg/kg.

PMID- 29028544
TI  - Predicting the effect of relaxation during frequency-selective adiabatic pulses.
AB  - Adiabatic half and full passages are invaluable for achieving uniform, B1
      insensitive excitation or inversion of macroscopic magnetization across a well
      defined range of NMR frequencies. To accomplish narrow frequency ranges with
      adiabatic pulses (<100Hz), long pulse durations at low RF power levels are
      necessary, and relaxation during these pulses may no longer be negligible. A
      numerical, discrete recursive combination of the Bloch equations for longitudinal
      and transverse relaxation with the optimized equation for adiabatic angular
      motion of magnetization is used to calculate the trajectory of magnetization
      including its relaxation during adiabatic hyperbolic secant pulses. The agreement
      of computer-calculated data with experimental results demonstrates that, in non
      viscous, small-molecule fluids, it is possible to model magnetization and
      relaxation by considering standard T1 and T2 relaxation in the traditional
      rotating frame. The proposed model is aimed at performance optimizations of
      applications in which these pulses are employed. It differs from previous reports
      which focused on short high-power adiabatic pulses and relaxation that is
      governed by dipole-dipole interactions, cross polarization, or chemical exchange.

PMID- 29028543
TI  - A pulse programmable parahydrogen polarizer using a tunable electromagnet and
      dual channel NMR spectrometer.
AB  - Applications of parahydrogen induced polarization (PHIP) often warrant conversion
      of the chemically-synthesized singlet-state spin order into net heteronuclear
      magnetization. In order to obtain optimal yields from the overall
      hyperpolarization process, catalytic hydrogenation must be tightly synchronized
      to subsequent radiofrequency (RF) transformations of spin order. Commercial NMR
      consoles are designed to synchronize applied waves on multiple channels and
      consequently are well-suited as controllers for these types of hyperpolarization
      experiments that require tight coordination of RF and non-RF events. Described
      here is a PHIP instrument interfaced to a portable NMR console operating with a
      static field electromagnet in the milliTesla regime. In addition to providing
      comprehensive control over chemistry and RF events, this setup condenses the PHIP
      protocol into a pulse-program that in turn can be readily shared in the manner of
      traditional pulse sequences. In this device, a TTL multiplexer was constructed to
      convert spectrometer TTL outputs into 24 VDC signals. These signals then
      activated solenoid valves to control chemical shuttling and reactivity in PHIP
      experiments. Consolidating these steps in a pulse-programming environment speeded
      calibration and improved quality assurance by enabling the B0/B1 fields to be
      tuned based on the direct acquisition of thermally polarized and hyperpolarized
      NMR signals. Performance was tested on the parahydrogen addition product of 2
      hydroxyethyl propionate-1-13C-d3, where the 13C polarization was estimated to be
      P13C=20+/-2.5% corresponding to 13C signal enhancement approximately 25 million
      fold at 9.1 mT or approximately 77,000-fold 13C enhancement at 3 T with respect
      to thermally induced polarization at room temperature.

PMID- 29028545
TI  - Penicillium expansum (compatible) and Penicillium digitatum (non-host) pathogen
      infection differentially alter ethylene biosynthesis in apple fruit.
AB  - The role of ethylene on inducing plant resistance or susceptibility to certain
      fungal pathogens clearly depends on the plant pathogen interaction with little or
      no-information available focused on the apple-Penicillium interaction. Taken
      advantage that Penicillium expansum is the compatible pathogen and P. digitatum
      is the non-host of apples, the present study aimed at deciphering how each
      Penicillium spp. could interfere in the fruit ethylene biosynthesis at the
      biochemical and molecular level. The infection capacity and different aspects
      related to the ethylene biosynthesis were conducted at different times post
      inoculation. The results show that the fruit ethylene biosynthesis was
      differently altered during the P. expansum infection than in response to other
      biotic (non-host pathogen P. digitatum) or abiotic stresses (wounding). The first
      symptoms of the disease due to P. expansum were visible before the initiation of
      the fruit ethylene climacteric burst. Indeed, the ethylene climacteric burst was
      reduced in response to P. expansum concomitant to an important induction of
      MdACO3 gene expression and an inhibition (ca. 3-fold) and overexpression (ca. 2
      fold) of ACO (1-Aminocyclopropane-1-carboxylic acid oxidase) and ACS (1
      Aminocyclopropane-1-carboxylic acid synthase) enzyme activities, indicating a
      putative role of MdACO3 in the P. expansum-apple interaction which may, in turn,
      be related to System-1 ethylene biosynthesis. System-1 is auto-inhibited by
      ethylene and is characteristic of non-climateric or pre-climacteric fruit.
      Accordingly, we hypothesise that P. expansum may 'manipulate' the endogenous
      ethylene biosynthesis in apples, leading to the circumvention or suppression of
      effective defences hence facilitating its colonization.

PMID- 29028546
TI  - Enzymatic characterization and crystal structure analysis of Chlamydomonas
      reinhardtii dehydroascorbate reductase and their implications for oxidative
      stress.
AB  - Dehydroascorbate reductase (DHAR) is a key enzyme for glutathione (GSH)-dependent
      reduction of dehydroascorbate (DHA) to recycled ascorbate (AsA) in plants, and
      plays a major role against the toxicity of reactive oxygen species (ROS).
      Previously, we proposed that the increase of AsA regeneration via enhanced DHAR
      activity modulates the ascorbate-glutathione cycle activity against
      photooxidative stress in Chlamydomonas reinhardtii. In the present work, we use
      site-directed mutagenesis and crystal structure analysis to elucidate the
      molecular basis of how C. reinhardtii DHAR (CrDHAR1) is involved in the
      detoxification mechanisms. Mutagenesis data show that the D21A, D21N and C22A
      mutations result in severe loss of the enzyme's function, suggesting crucial
      roles of Asp-21 and Cys-22 in substrate binding and catalysis. The mutant K11A
      also exhibits reduced redox activity (~50%). The crystal structure of apo CrDHAR1
      further provides insights into the proposed mechanism centering on the strictly
      conserved Cys-22, which is suggested to initiate the redox reactions of DHA and
      GSH. Furthermore, in vitro oxidation of the recombinant CrDHAR1 in the presence
      of 1 mM H2O2 has minor effects on the Km for the substrates but significantly
      reduces the kcat. The enzyme's activity and its mRNA abundance in the C.
      reinhardtii cells are increased by treatment with 0.2-1 mM H2O2 but decreased
      when H2O2 is >= 1.5 mM. The latter decrease is accompanied by oxidative damage
      and lower AsA concentrations. These biochemical and physiological data provide
      new insights into the catalytic mechanism of CrDHAR1, which protects the C.
      reinhardtii cells from oxidative stress-induced toxicity.

PMID- 29028547
TI  - (+)-Borneol improves the efficacy of edaravone against DSS-induced colitis by
      promoting M2 macrophages polarization via JAK2-STAT3 signaling pathway.
AB  - Compound edaravone injection (C.EDA), a compound preparation composed of
      edaravone (EDA) and (+)-Borneol with the mass ratio of 4: 1, displays a better
      anti-inflammatory activity than EDA. However, its precise mechanism remains to be
      further studied. In this work, we investigated whether (+)-Borneol could improve
      the efficacy of EDA against DSS-induced colitis. We found that C.EDA at 7.5 and
      15mg/kg could significantly relieve the disease activity index (DAI) and reduce
      the loss of body weight and colon length in a dose-dependent manner, while EDA or
      (+)-Borneol alone only had moderate effects even at the highest dose.
      Additionally, ELISA revealed that C.EDA could more dramatically decrease the
      protein levels of inflammatory cytokines and increase the levels of anti
      inflammatory cytokine than EDA or (+)-Borneol alone both in colon tissues and
      serum. H&E staining and IHC assay also indicated that C.EDA exhibited more
      prominent effects on increasing the population of M2 macrophages, decreasing M1
      macrophages infiltration and protecting intestinal barrier integrity.
      Furthermore, in vitro studied demonstrated that C.EDA, EDA or (+)-Borneol failed
      in inhibiting M1 macrophages activation but could specifically induce the
      activation of M2 macrophages in a STAT3-dependent manner. Knockdown the
      expression of STAT3 successfully abolished the effect of C.EDA and EDA on
      promoting M2 macrophages activation. Consistent with in vivo study, C.EDA
      exhibited a more efficient ability of inducing M2 macrophages polarization and
      STAT3 activation than EDA or (+)-Borneol alone in vitro. In conclusion, we
      confirmed that (+)-Borneol improved the efficacy of EDA against DSS-induced
      colitis by promoting M2 macrophages polarization via JAK2-STAT3 signaling
      pathway.

PMID- 29028548
TI  - Enhanced antitumor efficacy of arginine modified amphiphilic nanoparticles co
      delivering doxorubicin and iSur-pDNA via the multiple synergistic effect.
AB  - Arginine and alpha-tocopherol succinate (alpha-TOS) double grafted N-trimethyl
      chitosan chloride (TMC) nanoparticles (TAS NPs) were designed and developed for
      effective co-delivery of doxorubicin (DOX) and Survivin shRNA-expressing pDNA
      (iSur-pDNA). With DOX loading into the hydrophobic core and iSur-pDNA combining
      to the hydrophilic shell, TAS/DOX/pDNA NPs demonstrated favorable structural
      stability and sustained release properties in vitro. With the special non
      clathrin-dependent endocytosis, TAS/DOX/pDNA NPs presented higher cellular uptake
      and mainly distributed in ER and Golgi rather than lysosomes following
      internalization. The in vitro nuclear localization, gene silencing efficiency,
      cell apoptosis, and growth inhibition of tumor cells were significantly promoted
      by arginine modification. In the tumor-bearing mice model, TAS/DOX/pDNA NPs
      possessed the maximum antitumor efficiency as compared with single delivery of
      DOX or iSur-pDNA. Particularly, blank TAS NPs were selectively be toxic to tumor
      cells as evidenced by their capabilities to inhibit proliferation and induce
      apoptosis of tumor cells. The promising tumor treatment of TAS/DOX/pDNA NPs via a
      multiple synergistic manner arising from DOX and pDNA as well as the vectors
      would provide a potential strategy for a dual-delivery system to improve their
      therapeutic efficacies.

PMID- 29028549
TI  - MTA promotes chemotaxis and chemokinesis of immune cells through distinct calcium
      sensing receptor signaling pathways.
AB  - Mineral trioxide aggregate (MTA) has been introduced as a choice material for
      regenerative dentistry. To date, the diverse biological activities of MTA,
      including its anti-inflammatory effects, have been extensively discussed.
      However, there is limited insight into the link between MTA and immune cell
      migration. In this study, we report the role of MTA in enhancing both chemotactic
      and chemokinetic immune cell migration through distinct signaling pathways. By
      using versatile live imaging techniques, we demonstrated that MTA-mediated CaSR
      activation induced diverse downstream pathways to govern cell migratory capacity.
      In this context, Cdc42 generates cytoskeleton-driven cellular protrusions to
      steer directional cell migration (chemotaxis) whereas Ca2+-calmodulin dependent
      myosin light chain kinase induces cell contractility that plays an important role
      in speeding up the average migration speed (chemokinesis). Our findings
      illuminate an unrecognized role for MTA and the related CaSR signaling network in
      immune cell migration, providing evidence that can drive development of novel
      approaches to immunological therapy.

PMID- 29028550
TI  - Paternal exposure to environmental 17-alpha-ethinylestradiol concentrations
      modifies testicular transcription, affecting the sperm transcript content and the
      offspring performance in zebrafish.
AB  - The synthetic estrogen 17-alpha-ethinylestradiol (EE2), a major constituent in
      contraceptive pills, is an endocrine disrupting chemical (EDC) present in the
      aquatic environment at concentrations of ng/L. Developmental exposure to these
      low concentrations in fish can induce several disorders. Zebrafish (Danio rerio)
      is a perfect organism for monitoring the effects of environmental contaminants.
      Our hypothesis is that changes promoted by EE2 in the germ line of male adults
      could be transmitted to the unexposed progeny. We exposed male zebrafish to 2.5,
      5 and 10ng/L of EE2 during spermatogenesis and mated them with untreated females.
      Detailed progeny development was studied concentrating to survival, hatching and
      malformations. Due to the high incidence of lymphedemas within larvae, we
      performed qPCR analysis of genes involved in lymphatic development (vegfc and
      vegfr3) and endothelial cell migration guidance (cxcr4a and cxcl12b). Estrogen
      receptor (ER) transcript presence was also evaluated in sperm, testis and
      embryos. Progenies showed a range of disorders although at a low incidence:
      skeletal distortions, uninflated swimbladder, lymphedema formation, cartilage
      deformities and otolith tethering. Swimming evaluation revealed less active
      locomotion. All these processes are related to pathways involving ERs (esr1,
      esr2a and esr2b). mRNA analysis revealed that environmental EE2 causes the up
      regulation of esr1 an esr2b in testis and the increase of esr2b transcripts in
      sperm pointing to a link between lymphedema in embryos and ER expression
      impairment. We demonstrate that the effects induced by environmental toxicants
      can be paternally inherited and point to the changes on the sperm transcriptome
      as the responsible mechanism.

PMID- 29028551
TI  - Exploring the safety in numbers effect for vulnerable road users on a macroscopic
      scale.
AB  - A "Safety in Numbers" effect for a certain group of road users is present if the
      number of crashes increases at a lower rate than the number of road users. The
      existence of this effect has been invoked to justify investments in multimodal
      transportation improvements in order to create more sustainable urban
      transportation systems by encouraging walking, biking, and transit ridership. The
      goal of this paper is to explore safety in numbers effect for cyclists and
      pedestrians in areas with different levels of access to multimodal
      infrastructure. Data from Chicago served to estimate the expected number of
      crashes on the census tract level by applying Generalized Additive Models (GAM)
      to capture spatial dependence in crash data. Measures of trip generation,
      multimodal infrastructure, network connectivity and completeness, and
      accessibility were used to model travel exposure in terms of activity, number of
      trips, trip length, travel opportunities, and conflicts. The results show that a
      safety in numbers effect exists on a macroscopic level for motor vehicles,
      pedestrians, and bicyclists.

PMID- 29028552
TI  - Risk-reducing salpingo-oophorectomy in BRCA1 and BRCA2 mutated patients: An
      evidence-based approach on what women should know.
AB  - This review is focused on the ovarian cancer risk reduction management in BRCA
      mutation carriers and is intended to assist with clinical decision-making.
      Obviously, treatment decisions must be based on the available evidence. Despite
      risk-reducing salpingo-oophorectomy is firmly recommended, several separate
      questions can be raised to address the variety of intense controversy of this
      approach. A special emphasis lies in the effective preventive surgical measure
      against ovarian cancer risk, in an attempt to detect the optimal timing and
      mitigate the impact on patients. The long term implications of risk-reducing
      salpingo-oophorectomy as well as hormone replacement therapy are also actively
      debated. This is expected to represent an opportunity for improved management
      modelling of BRCA mutated patients.

PMID- 29028553
TI  - A nationwide analysis of intensive care unit admissions, 2009-2014 - The Korean
      ICU National Data (KIND) study.
AB  - PURPOSE: To evaluate unbiased information on the characteristics, procedures, and
      outcomes of intensive care unit (ICU) admissions in a long-term nationwide study.
      MATERIALS AND METHODS: Cohort study of all ICU admissions in patients >18years of
      age in Korea between August 1, 2009 and September 30, 2014 (1,553,673 ICU
      admissions in 1,265,509 patients). RESULTS: From August 2009 to September 2014,
      the age-standardized ICU admission rate was 744.6 per 100,000 person-years (869.5
      per 100,000 person-years in men and 622.0 per 100,000 person-years in women). The
      overall in-hospital mortality was 13.8% (14.1% in men and 13.5% in women). Among
      all Koreans, the ICU mortality rate was 102.9 per 100,000 person-years (122.5 per
      100,000 person years in men and 83.8 per 100,000 person years in women). The
      median ICU and hospital length of stay were 4 and 13days, respectively. The
      median cost per ICU admission was $5051, which increased steadily over the study
      period. There were marked differences by gender in ICU admission rates,
      aggressive support, and outcomes. CONCLUSIONS: Our study identified increasing
      trends in ICU admissions and utilization of advance life support systems that add
      to the burden of care in a developed society.

PMID- 29028554
TI  - Recovery capital pathways: Modelling the components of recovery wellbeing.
AB  - BACKGROUND: In recent years, there has been recognition that recovery is a
      journey that involves the growth of recovery capital. Thus, recovery capital has
      become a commonly used term in addiction treatment and research yet its
      operationalization and measurement has been limited. Due to these limitations,
      there is little understanding of long-term recovery pathways and their clinical
      application. METHODS: We used the data of 546 participants from eight different
      recovery residences spread across Florida, USA. We calculated internal
      consistency for recovery capital and wellbeing, then assessed their factor
      structure via confirmatory factor analysis. The relationships between time,
      recovery barriers and strengths, wellbeing and recovery capital, as well as the
      moderating effect of gender, were estimated using structural equations modelling.
      RESULTS: The proposed model obtained an acceptable fit (chi2 (141,
      N=546)=533.642, p<0.001; CMIN/DF=3.785; CFI=0.915; TLI=0.896; RMSEA=0.071).
      Findings indicate a pathway to recovery capital that involves greater time in
      residence ('retention'), linked to an increase in meaningful activities and a
      reduction in barriers to recovery and unmet needs that, in turn, promote recovery
      capital and positive wellbeing. Gender differences were observed. CONCLUSIONS: We
      tested the pathways to recovery for residents in the recovery housing population.
      Our results have implications not only for retention as a predictor of sustained
      recovery and wellbeing but also for the importance of meaningful activities in
      promoting recovery capital and wellbeing.

PMID- 29028555
TI  - Shifting characteristics of ecstasy users ages 12-34 in the United States, 2007
      2014.
AB  - BACKGROUND: Ecstasy/MDMA has been one of the most prevalent party drugs for
      decades, and powder ecstasy recently increased in popularity. We examined trends
      in use to determine who to best target for prevention and harm reduction.
      METHODS: Secondary analysis of the 2007-2014 National Survey on Drug Use and
      Health, a repeated cross-sectional, nationally representative probability sample,
      was conducted. Linear trends in past-year ecstasy use and trends in demographic
      and other past-year substance use characteristics among ecstasy users were
      examined among participants ages 12-34 (N=332,560). RESULTS: Past-year prevalence
      of ecstasy use was stable across years at 2% (P=0.693). Over time, the proportion
      of ecstasy users with a college degree increased from 11.5% in 2007/08 to 24.5%
      in 2013/14 (P<0.001). The proportion of users who were age 12-17 decreased, as
      did proportions of users who are non-Hispanic black, and reported income
      <$20,000/year (Ps<0.001). Prevalence of past-year use of marijuana, LSD,
      ketamine, and DMT/AMT/Foxy increased among ecstasy users (Ps<0.05); DMT/AMT/Foxy
      use increased more than four-fold from 2.1% in 2007/08 to 8.7% in 2013/14.
      Perception of great risk associated with LSD use decreased among users and ease
      of obtaining LSD increased (Ps<0.05). Past-year use of 5 or more other substances
      also increased over time (P<0.05). CONCLUSIONS: Ecstasy use in the US appears to
      be increasing among those with college degrees and use of other substances among
      ecstasy users is growing-particularly use of otherwise rare substances such as
      tryptamines. Results inform prevention and harm reduction strategies in this
      increasingly shifting group of ecstasy users.

PMID- 29028556
TI  - Buspirone maintenance does not alter the reinforcing, subjective, and
      cardiovascular effects of intranasal methamphetamine.
AB  - BACKGROUND: Medications development efforts for methamphetamine-use disorder have
      targeted central monoamines because these systems are directly involved in the
      effects of methamphetamine. Buspirone is a dopamine autoreceptor and D3 receptor
      antagonist and partial agonist at serotonin 1A receptors, making it a logical
      candidate medication for methamphetamine-use disorder. Buspirone effects on abuse
      related behaviors of methamphetamine have been mixed in clinical and preclinical
      studies. Experimental research using maintenance dosing, which models therapeutic
      use, is limited. This study evaluated the influence of buspirone maintenance on
      the reinforcing effects of methamphetamine using a self-administration procedure,
      which has predictive validity for clinical efficacy. The impact of buspirone
      maintenance on the subjective and cardiovascular response to methamphetamine was
      also determined. METHODS: Eight research participants (1 female) reporting recent
      illicit stimulant use completed a placebo-controlled, crossover, double-blind
      protocol in which the pharmacodynamic effects of intranasal methamphetamine (0,
      15, and 30mg) were assessed after at least 6days of buspirone (0 and 45mg/day)
      maintenance. RESULTS: Intranasal methamphetamine functioned as a reinforcer and
      produced prototypical stimulant-like subjective (e.g., increased ratings of Good
      Effects and Like Drug) and cardiovascular (e.g., elevated blood pressure)
      effects. These effects of methamphetamine were similar under buspirone and
      placebo maintenance conditions. Maintenance on buspirone was well tolerated and
      devoid of effects when administered alone. CONCLUSIONS: These data suggest that
      buspirone is unlikely to be an effective pharmacotherapy for methamphetamine-use
      disorder. Given the central role of monoamines in methamphetamine-use disorder,
      it is reasonable for future studies to continue to target these systems.

PMID- 29028557
TI  - Understanding the association between stunting and child development in low- and
      middle-income countries: Next steps for research and intervention.
AB  - Stunting, caused by experiences of chronic nutritional deprivation, affects
      approximately 25% of children under age five globally (i.e., 156 million
      children). In this review, evidence of a relationship between stunting and child
      development in low- and middle-income countries is summarized, and issues for
      further research are discussed. We focus on studies that measured low height-for
      age among children less than 5 years old as the exposure and gross/fine motor
      skills, psychosocial competencies, cognitive abilities, or schooling and learning
      milestones as the outcomes. This review highlights three key findings. First, the
      variability in child development tools and metrics used among studies and the
      differences in the timing and frequency of the assessments complicate comparisons
      across study findings. Second, considerable evidence from across many countries
      supports an association between stunting and poor child development despite
      methodological differences and heterogeneity in the magnitude of associations.
      Further, effect sizes differ by developmental domain with greater associations
      shown for cognitive/schooling outcomes. How stunting influences child
      development, which domains of child development are more affected, and how the
      various domains of child development influence one another require further
      experimental research to test causal pathways. Finally, there is mixed evidence
      of the additive effect of nutrition + stimulation interventions on child
      development. However, understanding best methods for improving child
      developmental outcomes - either through nutrition programs or through integrated
      nutrition + psychosocial stimulation programs (or nutrition + other program
      interventions) - is a key area of further inquiry. Given that nearly 40% of
      children under age five suffer from loss of developmental potential - for which
      stunting is likely one of the key risk factors - reductions in stunting could
      have tremendous implications for child development and human capital formation,
      particularly in low- and middle-income countries.

PMID- 29028558
TI  - Determinants of trust in the flu vaccine for African Americans and Whites.
AB  - Trust is thought to be a major factor in vaccine decisions, but few studies have
      empirically tested the role of trust in adult immunization. Utilizing a 2015
      national survey of African American and White adults (n = 1630), we explore
      multiple dimensions of trust related to influenza immunization, including
      generalized trust, trust in the flu vaccine, and trust in the vaccine production
      process. We find African Americans report lower trust than Whites across all
      trust measures. When considering demographic, racial, and ideological predictors,
      generalized trust shows statistically significant effects on both trust in the
      flu vaccine and trust in the vaccine process. When controlling for demographic,
      racial, and ideological variables, higher generalized trust was significantly
      associated with higher trust in the flu vaccine and the vaccine process. When
      controlling for generalized trust, in addition to the baseline covariates,
      psychosocial predictors (i.e. risk perception, social norms, knowledge) are
      significant predictors of trust in flu vaccine and trust in the vaccine process,
      with significant differences by race. These findings suggest that trust in
      vaccination is complex, and that significant differences in trust between White
      and African American adults may be contributing to disparities in influenza
      immunization.

PMID- 29028560
TI  - Racial discrimination and cortisol output: A meta-analysis.
AB  - RATIONALE: Although the relation between stress and physiology is well
      documented, attempts at understanding the link between racial discrimination and
      cortisol output, specifically, have produced mixed results, likely due to study
      characteristics such as racial/ethnic composition of the samples (e.g., African
      American, Latino), measures of discrimination, and research design (e.g., cross
      sectional, experimental). OBJECTIVES: To estimate the overall association between
      racial discrimination and cortisol output among racial/ethnic minority
      individuals and to determine if the association between racial discrimination and
      cortisol output is moderated by age, race/ethnicity, type of discrimination
      measure, sex, and research design. RESULTS: Using a random effects model, the
      overall effect size based on k = 16 studies (19% unpublished) and N = 1506
      participants was r- = 0.040, 95% CI = -0.038 to 0.117. Studies were conducted
      predominantly in the U.S. (81%). Notably, experimental studies (r- = 0.267)
      exhibited larger effect sizes compared to non-experimental studies (r- = -0.007).
      Age, race/ethnicity, type of discrimination measure, and sex did not moderate the
      effect sizes. CONCLUSION: This meta-analysis provides evidence that the
      measurement of the association between racial discrimination and cortisol is
      complex, and it offers valuable insight regarding methods and designs that can
      inform future research on this topic. Limitations and future directions are
      discussed.

PMID- 29028559
TI  - "What's the right thing to do?" Correctional healthcare providers' knowledge,
      attitudes and experiences caring for transgender inmates.
AB  - RATIONAL: Incarcerated transgender individuals may need to access physical and
      mental health services to meet their general and gender-affirming (e.g.,
      hormones, surgery) medical needs while incarcerated. OBJECTIVE: This study sought
      to examine correctional healthcare providers' knowledge of, attitudes toward, and
      experiences providing care to transgender inmates. METHOD: In 2016, 20
      correctional healthcare providers (e.g., physicians, social workers,
      psychologists, mental health counselors) from New England participated in in
      depth, semi-structured interviews examining their experiences caring for
      transgender inmates. The interview guide drew on healthcare-related interviews
      with recently incarcerated transgender women and key informant interviews with
      correctional healthcare providers and administrators. Data were analyzed using a
      modified grounded theory framework and thematic analysis. RESULTS: Findings
      revealed that transgender inmates do not consistently receive adequate or gender
      affirming care while incarcerated. Factors at the structural level (i.e., lack of
      training, restrictive healthcare policies, limited budget, and an unsupportive
      prison culture); interpersonal level (i.e., custody staff bias); and individual
      level (i.e., lack of transgender cultural and clinical competence) impede
      correctional healthcare providers' ability to provide gender-affirming care to
      transgender patients. These factors result in negative health consequences for
      incarcerated transgender patients. CONCLUSIONS: Results call for transgender
      specific healthcare policy changes and the implementation of transgender
      competency trainings for both correctional healthcare providers and custody staff
      (e.g., officers, lieutenants, wardens).

PMID- 29028561
TI  - Stability and drug release studies of an antimycotic nanomedicine using HPLC,
      dynamic light scattering and atomic force microscopy.
AB  - Much attention has been paid to nanoparticle-based drug delivery systems to
      selectively deliver drugs to target organs and tissues. In this study, AmBisome,
      an antimycotic nanomedicine containing amphotericin B, was chosen as a typical
      nanomedicine, and analyzed using dynamic light scattering (DLS), an easy method
      to measure size, and size distribution, atomic force microscopy (AFM) and high
      performance liquid chromatography (HPLC). AFM allowed the analysis of shape,
      besides a detailed size and size distribution. HPLC is useful to quantify the
      released amount of amphotericin B as it succeeded in a rapid separation of
      AmBisome and free amphotericin B. The aggregation or collapse of AmBisome and
      release of amphotericin B occurred upon 75% methanol addition or dilution with
      buffer around pH 4. Therefore, it is important to analyze nanomedicines using
      multiple analytical methods, and to integrate them for the quality and quantity
      evaluation of nanomedicines.

PMID- 29028562
TI  - Common and differential factors associated with abstinence and poly drug use
      among Australian adolescents.
AB  - BACKGROUND: Social norms relating to youth substance use are changing. In
      Australia, alcohol use among adolescents has fallen dramatically and tobacco and
      cannabis use have also reduced, albeit more moderately. The aim of the present
      study was to identify (i) factors associated with compliance with recommendations
      for zero intake of alcohol, tobacco, and cannabis and (ii) factors associated
      with poly drug use (intake of all three substances). METHODS: As part of the
      Young Minds Matter Study, a self-report survey was administered to 1661
      Australian adolescents aged 15-17 years. The survey included items relating to:
      substance use; psychological, social, and protective factors; and demographic
      characteristics. Probit regression analyses were conducted to generate a model of
      factors associated with abstinence from all three substances and a model of
      factors associated with the use of all three substances. RESULTS: While there
      were substantial differences between the two models indicating that different
      factors may influence the initiation of substance use versus poly drug use, there
      were also several common factors that operated in opposite directions. These were
      child age, degree of parental supervision and monitoring, the experience of
      externalising problems, and a diagnosis of major depression. CONCLUSION: The
      results highlight the potential utility of targeting high-risk youth by
      identifying (i) parents' supervision and monitoring behaviours and (ii)
      children's externalising problems and symptoms of depression. Directly addressing
      these factors in substance-use interventions may delay or prevent initiation
      while also reducing the likelihood of adolescents engaging in poly drug use.

PMID- 29028563
TI  - Exploring the relationship between online buyers and sellers of image and
      performance enhancing drugs (IPEDs): Quality issues, trust and self-regulation.
AB  - BACKGROUND: Online drug markets are expanding the boundaries of drug supply
      including the sale and purchase of image and performance enhancing drugs (IPEDs).
      However, the role of the internet in IPED markets, and in particular the ways in
      which these substances are supplied via the surface web, has rarely been
      considered. This article examines the online IPED market in order to inform drug
      policy and to provide a nuanced understanding of retailers involved, particularly
      exploring the relationship between buyers and sellers. METHODS: This paper is
      based on two extensive research projects conducted in the Netherlands and
      Belgium. The first project focuses on muscle drugs and is based on 64 IPED
      dealing cases, semi-structured interviews with authorities (N=32), and dealers
      (N=15), along with an analysis of 10 steroid-selling websites. The second
      research project primarily focuses on weight loss drugs and sexual enhancers in
      the Netherlands, and relies on interviews with authorities (N=38), suppliers
      (N=30), and consumers (N=10), analysis of 69 criminal case files, and an online
      analysis. RESULTS: In the literature, the illicit online sale of IPEDs is
      generally associated with illegal online pharmacies that try to mislead buyers.
      While confirmed in our research, we also illustrate that there are online
      suppliers who invest in customer relationships and services, and that users are
      aware of the illegal nature of their business. These e-vendors incorporate a
      'social supply business model' by providing the best possible service to their
      customers and attempting to minimise risks in order to attract, satisfy and
      maintain customers. CONCLUSION: As it is likely that users will continue to make
      use of the internet to order IPEDs, regardless of closing down selling websites,
      it is first of all important to counteract these online sources by educating all
      types of consumers and providing harm reduction services.

PMID- 29028566
TI  - Concept mapping to promote meaningful learning, help relate theory to practice
      and improve learning self-efficacy in Asian mental health nursing students: A
      mixed-methods pilot study.
AB  - OBJECTIVES: Student nurses are provided with a great deal of knowledge within
      university, but they can find it difficult to relate theory to nursing practice.
      This study aimed to test the appropriateness and feasibility of assessing Novak's
      concept mapping as an educational strategy to strengthen the theory-practice
      link, encourage meaningful learning and enhance learning self-efficacy in nursing
      students. DESIGN: This pilot study utilised a mixed-methods quasi-experimental
      design. SETTING: The study was conducted in a University school of Nursing in
      Hong Kong. PARTICIPANTS: A total of 40 third-year pre-registration Asian mental
      health nursing students completed the study; 12 in the concept mapping (CM) group
      and 28 in the usual teaching methods (UTM) group. METHODS: The impact of concept
      mapping was evaluated thorough analysis of quantitative changes in students'
      learning self-efficacy, analysis of the structure and contents of the concept
      maps (CM group), a quantitative measure of students' opinions about their
      reflective learning activities and content analysis of qualitative data from
      reflective written accounts (CM group). RESULTS: There were no significant
      differences in self-reported learning self-efficacy between the two groups
      (p=0.38). The concept mapping helped students identify their current level of
      understanding, but the increased awareness may cause an initial drop in learning
      self-efficacy. The results highlight that most CM students were able to
      demonstrate meaningful learning and perceived that concept mapping was a useful
      reflective learning strategy to help them to link theory and practice.
      CONCLUSIONS: The results provide preliminary evidence that the concept mapping
      approach can be useful to help mental health nursing students visualise their
      learning progress and encourage the integration of theoretical knowledge with
      clinical knowledge. Combining concept mapping data with quantitative measures and
      qualitative reflective journal data appears to be a useful way of assessing and
      understanding the effectiveness of concept mapping. Future studies should utilise
      a larger sample size and consider using the approach as a targeted intervention
      immediately before and during clinical learning placements.

PMID- 29028565
TI  - Human papillomavirus vaccine initiation in Asian Indians and Asian
      subpopulations: a case for examining disaggregated data in public health
      research.
AB  - OBJECTIVES: Vaccine disparities research often focuses on differences between the
      five main racial and ethnic classifications, ignoring heterogeneity of
      subpopulations. Considering this knowledge gap, we examined human papillomavirus
      (HPV) vaccine initiation in Asian Indians and Asian subpopulations. STUDY DESIGN:
      National Health Interview Survey data (2008-2013), collected by the National
      Center for Health Statistics, were analyzed. METHODS: Multiple logistic
      regression analysis was conducted on adults aged 18-26 years (n = 20,040).
      RESULTS: Asian Indians had high income, education, and health insurance coverage,
      all positive predictors of preventative health engagement and vaccine uptake.
      However, we find that Asian Indians had comparatively lower rates of HPV vaccine
      initiation (odds ratio = 0.41; 95% confidence interval = 0.207-0.832), and
      foreign-born Asian Indians had the lowest rate HPV vaccination of all
      subpopulations (2.3%). CONCLUSIONS: Findings substantiate the need for research
      on disaggregated data rather than evaluating vaccination behaviors solely across
      standard racial and ethnic categories. We identified two populations that were
      initiating HPV vaccine at abysmal levels: foreign-born persons and Asian Indians.
      Development of culturally appropriate messaging has the potential to improve
      these initiation rates and improve population health.

PMID- 29028564
TI  - Assessing police officers' attitudes and legal knowledge on behaviors that impact
      HIV transmission among people who inject drugs.
AB  - BACKGROUND: Policing practices such as syringe confiscation and arrest can act as
      important social-structural drivers of HIV risk among people who inject drugs
      (PWID). However, police referral to treatment and other services may improve the
      health of PWID. Little is known about the role of modifiable attitudinal and
      knowledge factors in shaping officer behavior. Using baseline findings from a
      police education program (PEP), we assessed relationships between drug policy
      knowledge and attitudes towards public health interventions with self-reported
      syringe confiscation, drug arrest, and service referral among street-level police
      in Tijuana, Mexico. METHODS: Between February, 2015 and May, 2016 we surveyed
      1319 police officers who reported syringe contact. The self-administered survey
      focused on attitudes, knowledge, and behaviors related to drug policy, public
      health, and occupational safety. We used ordinal logistic regression to model the
      odds of syringe confiscation, arrest for heroin possession, and referring PWID to
      health/social programs. RESULTS: The sample was mostly male (87%) and had at
      least a high school education (80%). In the last six months, a minority reported
      always/sometimes confiscating syringes (49%), arresting someone for heroin
      possession (43%), and referring PWID to health and social programs (37%). Those
      reporting needlestick injuries (NSI) had 1.38 (95% CI: 1.02-1.87) higher odds of
      reporting syringe confiscation. Officers who had favorable views on laws that
      treat addiction as a public health issue had lower odds (aOR=0.78; 95% CI: 0.59
      1.03) of arresting PWID. Those agreeing that it was their role to refer PWID to
      health and social programs had higher odds of reporting such referrals (aOR:
      3.32, 95% CI: 2.52-4.37). Legal knowledge was not associated with these
      practices. CONCLUSION: Changing drug policy and knowledge may be insufficient in
      shifting police behavior. Modifying officers' occupational risks and attitudes
      towards harm reduction interventions can facilitate efforts to align police
      practices with PWID health.

PMID- 29028567
TI  - Accessibility of prison healthcare for elderly inmates, a qualitative assessment.
AB  - Aging in custody and the rising population of elderly prisoners are creating
      compelling challenges for criminal justice, prison and public healthcare systems.
      Geriatric syndrome and higher prevalence of co-morbidities amongst older inmates
      result in heightened vulnerability in prison environments. Empirical research
      addressing older adults' access to medical care in detention is scarce;
      therefore, this study assessed access to medical care in prison from the
      perspective of older prisoners in Switzerland. We interviewed a sample of 35
      older inmates (average age 61 years) on their experience of healthcare
      accessibility in prison; data were qualitatively analysed and major themes
      regarding evaluation of their access to medical services were extracted. Our
      findings identified three barriers to accessing health services in prison
      including psychological obstacles, negative consequences of healthcare
      utilization, and environmental hurdles. We advocate facilitating older inmates'
      access to medical care in order to relieve the psychological burden of seeking
      health services in detention and adequately informing them of their right to
      demand these services, thereby lessening the negative consequences of their
      requests. We suggest further training of prison and medical staff for better
      management of age-related issues in prison can ease the environmental obstacles.

PMID- 29028568
TI  - Virulence genotypes and antimicrobial susceptibility patterns of Arcobacter
      butzleri isolated from seafood and its environment.
AB  - Arcobacter butzleri is an emerging pathogen isolated from animals, food and the
      environment. In this study, 147 A. butzleri isolated from seafood and the coastal
      environment were tested for the presence of ten putative virulence genes (cadF,
      cj1349, ciaB, mviN, pldA, tlyA, hecA, hecB, irgA, iroE) and antimicrobial
      susceptibilities. Majority of the isolates harbored mviN (100%), cj1349 (97.2%),
      ciaB (95.9%), tlyA (91.8%), pldA (91.1%) and cadF (89.7%). Lower detection rates
      were observed for hecA (10.8%), hecB (19%), iroE (12.9%) and irgA (17.6%). Three
      A. butzleri isolates harbored all ten virulence genes. The occurrence of cj1349,
      ciaB, pldA, tlyA and hecA genes was significantly different (P<=0.05) among the
      isolates from different sources. All (100%) A. butzleri isolates were resistant
      to vancomycin, cephalothin, cefoxitin and sulphamethizole and susceptible to
      polymyxin-B, kanamycin, streptomycin, gentamicin, tetracycline and imipenem.
      Resistance to clinically important antibiotics such as cefotaxime (99.3%),
      ceftazidime (87.7%), nalidixic acid (70.7%), ampicillin (72.1%), ertapenem and
      amoxicillin-clavulanic acid (41.9%) was observed in A. butzleri from the
      environment. The isolates were highly susceptible to norfloxacin (97.9%) and
      colistin (97.2%), followed by ciprofloxacin (88.4%), meropenem (74.8%),
      chloramphenicol (72.7%) and erythromycin (69.3%). A. butzleri from different
      sources were not significantly different with respect to their antimicrobial
      susceptibility patterns. Multidrug resistance was observed in 66 (81.4%) isolates
      from fish, 29 (72.5%) isolates from shellfish and 17 (65.3%) isolates from
      coastal water. A. butzleri harboring virulence genes and resistance to multiple
      antibiotics found in seafood could be a potential health risk to seafood handlers
      and consumers. Continuous monitoring of seafood for potentially pathogenic A.
      butzleri is important to understand the evolution of antibiotic resistance in
      this emerging food pathogen and to determine the antimicrobial therapy regimen in
      the event of food-borne A. butzleri infections.

PMID- 29028569
TI  - Occurrence of transferable antibiotic resistances in commercialized ready-to-eat
      mealworms (Tenebrio molitor L.).
AB  - The present study aimed to assess the occurrence of transferable determinants
      conferring resistance to tetracyclines, macrolide-lincosamide-streptogramin B,
      vancomycin, beta-lactams, and aminoglycosides in 40 samples of commercialized
      edible mealworms (Tenebrio molitor L.) purchased from European Union (EU) and non
      EU producers. A high prevalence of tet(K) was observed in all of the samples
      assayed, with percentages of PCR-based positivity that ranged from 80% (samples
      from Thailand) to 100% (samples from the Netherlands, Belgium and France). For
      macrolides, erm(B) prevailed, being detected in 57.5% of the samples assayed,
      whereas erm(A) and erm(C) were detected with lower frequencies. Genes for
      resistance to vancomycin were only detected in samples produced in France and
      Belgium, with 90% and 10% of the samples being positive for vanA, respectively.
      Beta-lactamase genes were found with low occurrence, whereas the gene aac-aph,
      conferring high resistance to aminoglycosides, was found in 40% of the samples
      produced in the Netherlands and Belgium and 20% of the samples produced in
      Thailand. The results of Principal Coordinate Analysis and Principal Component
      Analysis depicted a clean separation of the samples collected from the four
      producers based on the distribution of the 12 AR determinants considered. Given
      the growing interest on the use of mealworms as a novel protein source, AR
      detection frequencies found in the present study suggest further investigation
      into the use of antibiotics during rearing of this insect species and more
      extensive studies focused on the factors that can affect the diffusion of
      transferable ARs in the production chain. Until such studies are completed,
      prudent use of antibiotics during rearing of edible insects is recommended.

PMID- 29028570
TI  - Bovine ovarian follicular growth and development correlate with lysophosphatidic
      acid expression.
AB  - The basis of successful reproduction is proper ovarian follicular growth and
      development. In addition to prostaglandins and vascular endothelial growth
      factor, a number of novel factors are suggested as important regulators of
      follicular growth and development: PGES, TFG, CD36, RABGAP1, DBI and BTC. This
      study focuses on examining the expression of these factors in granulosa and
      thecal cells that originate from different ovarian follicle types and their link
      with the expression of lysophosphatidic acid (LPA), known local regulator of
      reproductive functions in the cow. Ovarian follicles were divided into healthy,
      transitional, and atretic categories. The mRNA expression levels for PGES, TFG,
      CD36, RABGAP1, DBI and BTC in granulosa and thecal cells in different follicle
      types were measured by real-time PCR. The correlations among expression of
      enzymes synthesizing LPA (autotaxin, phospholipase A2), receptors for LPA and
      examined factors were measured. Immunolocalization of PGES, TFG, CD36, RABGAP1,
      DBI and BTC was examined by immunohistochemistry. We investigated follicle-type
      dependent mRNA expression of factors potentially involved in ovarian follicular
      growth and development, both in granulosa and thecal cells of bovine ovarian
      follicles. Strong correlations among receptors for LPA, enzymes synthesizing LPA,
      and the examined factors in healthy and transitional follicles were observed,
      with its strongest interconnection with TFG, DBI and RABGAP1 in granulosa cells,
      and TFG in thecal cells; whereas no correlations in atretic follicles were
      detected. A greater number of correlations were found in thecal cells than in
      granulosa cells as well as in healthy follicles than in transitional follicles.
      These data indicate the role of LPA in the growth, development and physiology of
      the bovine ovarian follicle.

PMID- 29028571
TI  - Identifying ovarian tissue in the bitch using anti-Mullerian hormone (AMH) or
      luteinizing hormone (LH).
AB  - Reliable methods for determining whether or not a bitch has ovarian tissue
      present are needed for cases with unknown neutering status. Vaginal cytology
      consistent with heat is indicative of functional ovarian tissue. Other methods
      are required when the bitch is not presented in suspected heat. Progesterone can
      be analyzed during 2 months after suspected heat. During other stages, assays for
      the analyses of anti-Mullerian hormone (AMH) and luteinizing hormone (LH) have
      been used. The AMH assay is expected to give detectable concentrations (positive)
      in bitches with ovarian tissue, and the LH assay should give negative results in
      intact bitches, except during the pre-ovulatory LH peak. The aim of the present
      study was to study the diagnostic efficiency for detecting ovarian tissue in
      bitches using an AMH assay developed for human samples, and a semi-quantitative
      rapid immune migration (RIMTM) LH assay developed for use in dogs. An AMH
      concentration of >=0.1 MUg/L, and an LH concentration of <=1 MUg/L, was set as
      the cut-off for presence of ovarian tissue. Client or staff owned bitches were
      included (N = 125). There were 73 intact bitches that were classified as being in
      heat (N = 25); in luteal phase (N = 12); or in anestrus (N = 36), and 52 spayed
      bitches that showed no clinical signs of estrogen influence. In total 64 of the
      73 intact bitches (88%) were correctly identified using AMH, and 70/73 (96%)
      intact bitches were correctly identified using the LH assay. Excluding bitches in
      heat, the corresponding figures were 42/48 (88%) for AMH and 48/48 (100%) for LH.
      Of the 52 spayed bitches, 51 (98%) were correctly identified using the AMH assay
      and 49 (94%) were correctly identified using the LH assay. In this population,
      the predictive value of a positive AMH for intact bitches was 98%, and of a
      negative AMH for spayed bitches was 85%. Excluding bitches in heat, the
      predictive value of a negative LH test for intact bitches was 94%, and the
      predictive value of a positive LH test for identifying spayed bitches was 100%.
      It was concluded that analyses of AMH and LH are useful for detecting ovarian
      tissue in bitches, but that low concentrations of AMH may be obtained in intact
      bitches, classifying them as spayed. For LH, bitches in suspected estrus should
      not be tested to avoid the pre-ovulatory LH-surge, that otherwise may cause
      intact bitches being incorrectly identified as spayed.

PMID- 29028572
TI  - Supramolecular gels: using an amide-functionalized imidazolium-based surfactant.
AB  - Studies on supramolecular gel aggregates via supramolecular interactions are very
      fascinating and impressive. The interactions of gelator with solvent and
      inorganic salt can functionalize, activate, or control the properties of
      supramolecular gels. A lot of work on this area has been done, but all these
      contributions are only at an early stage. In this work, we tuned the gel
      formation conditions and properties by using low-molecular-weight gelator
      (LMWGs), amide-functionalized imidazolium-based surfactant, viz., N-cetyl-N'
      acetamido imidazolium bromide ([N-C16, N'-CONH2-Im]Br), in different solvents and
      with inorganic salt additives. Under chemical (Cu2+/H2O2) and physical
      (temperature) stimuli, gel-sol phase transition occurred in the gel formed from 2
      wt% [N-C16, N'-CONH2-Im]Br in the solvent formamide (FM). Accompanied with
      increased mechanical strength of the gels, morphology alternation from initial
      straight stripe-shaped structures to curly belt-like textures was observed in the
      addition of CuBr2. From Small-angle X-ray scattering (SAXS) measurements, bilayer
      units with interdigitated hydrocarbon tails of the gelator were testified to
      appear in the gels. Comparative experiments demonstrate that the pi-pi
      interaction, H-bonding, and hydrophobic interaction between the gelator molecules
      are the main driving forces for the gelation. The low-cost gelator, facile
      preparation, and coordination-driven assembly process make the robust gel a good
      candidate in various applications, such as material templates and drug
      deliveries.

PMID- 29028573
TI  - The first protection-free synthesis of magnetic bifunctional l-proline as a
      highly active and versatile artificial enzyme: Synthesis of imidazole
      derivatives.
AB  - l-Proline is a bifunctional versatile organocatalyst that could promote a variety
      of useful transformations. Some passive and dynamic interactions between this
      simple amino acid and different substrates, which are necessary to enzymatic
      reactions, have given it "the simplest enzyme" title. Herein we presented the
      first report on the synthesis of magnetic bifunctional l-proline as an artificial
      enzyme without requiring any protection/deprotection steps according to an
      operationally simple process. This magnetic nano-biocatalyst is a promising
      catalyst that in a case study was successfully applied for the synthesis of 2,4,5
      trisubstituted and 1,2,4,5-tetrasubstituted imidazoles in the 70-99% and 60-90%
      yields respectively, which it could be extended to the variety of l-proline-based
      organic transformations. The synergic effect of bifunctional l-proline shell as
      catalytic active site and magnetite nanoparticles core, which could function as
      protein mimics endow it high efficiency, versatility, recoverability, reusability
      and good turnover frequency, which are necessary characters for artificial
      enzymes' designing.

PMID- 29028574
TI  - Gravity-directed separation of both immiscible and emulsified oil/water mixtures
      utilizing coconut shell layer.
AB  - Pressure-driven and lower flux of superwetting ultrafiltration membranes in
      various emulsions separation are long-standing issues and major barriers for
      their large-scale utilization. Even though currently reported membranes have
      achieved great success in emulsions separeation, they still suffer from low flux
      and complex fabrication process resulting from their smaller nanoscale pore size.
      Herein, utilizition of coconut shell as a novel biomaterial for developing into a
      layer through the simple smashing, cleaning and stacking procedures, which not
      only could avoid the complexity of film making process, but also could realize
      efficient gravity-directed separation of both immiscible oil/water mixtures and
      water-in-oil emulsions with high flux. Specifically, the layer acted as "water
      removing" type filtrate material with excellent underwater superoleophobicity,
      exhibiting high efficiency for various immiscible oil/water mixtures separation
      and larger oil intrusion pressure. More importantly, the layer could also serve
      as adsorbent material with underoil superhydrophilicity, achieving gravity
      directed kinds of water-in-oil emulsions separation with high separation
      efficiency (above 99.99%) and higher flux (above 1620L/m2h), even when their pore
      sizes are larger than that of emulsified droplets. We deeply believe that this
      study would open up a new strategy for both immiscible oil/water mixtures and
      water-in-oil emulsions separation.

PMID- 29028575
TI  - Green synthesis of highly dispersed ytterbium and thulium co-doped sodium yttrium
      fluoride microphosphors for in situ light upconversion from near-infrared to blue
      in animals.
AB  - We report a simple, low cost and environmentally friendly method to prepare
      NaYF4:Yb3+, Tm3+ upconversion microphosphors (UCMPs) by thermal decomposition of
      rare earth-trifluoroacetate precursors using paraffin as the high boiling non
      coordinating solvent. The UCMPs exhibited cubic phase with defined shape and
      bright upconversion luminescence. After coating with amphiphilic polymers of
      phospholipid-polyethylene glycol, the NaYF4:Yb3+, Tm3+ UCMPs were highly
      dispersed in aqueous solutions and exhibited low cytotoxicity. Furthermore, we
      explored the use of the micro-injected micro-sized NaYF4:Yb3+, Tm3+ particles for
      converting of near infrared into blue light in mice brain. The in vivo
      macroscopic upconversion luminescence imaging results showed that UCMPs located
      at 1mm depth in the brain could be clearly distinguished. Microscopic
      upconversion luminescence imaging of the brain sections in vitro revealed that
      the UCMPs embedded at the particular location in brain tissues of mice were
      stable without significant diffusion in two weeks.

PMID- 29028577
TI  - CO2 adsorption at nitrogen-doped carbons prepared by K2CO3 activation of urea
      modified coconut shell.
AB  - This article reports on the synthesis and characterization of porous nitrogen
      doped carbons synthesized by carbonization of coconut shell followed by urea
      modification and K2CO3 activation. The as-synthesized samples were carefully
      characterized by various techniques. This series of samples demonstrate high CO2
      uptake at 1bar, up to 3.71mmol/g at 25 degrees C in addition to 5.12mmol/g at 0
      degrees C. Furthermore, these sorbents possess fast CO2 adsorption kinetics,
      stable reusability, moderate heat of CO2 adsorption, reasonable CO2/N2
      selectivity, and high dynamic CO2 capture capacity under simulated flue gas
      conditions. It is found that, in addition to nitrogen content and narrow
      micropore volume, the pore size distribution of narrow micropore also plays a
      major role in determining the CO2 capture capacity under ambient condition. This
      work is intended to provide useful information and to inspire ways to develop new
      carbonaceous sorbents for removing CO2 from combustion flue gas.

PMID- 29028576
TI  - Bioelectrochromic hydrogel for fast antibiotic-susceptibility testing.
AB  - Materials science offers new perspectives in the clinical analysis of
      antimicrobial sensitivity. However, a biomaterial with the capacity to respond to
      living bacteria has not been developed to date. We present an electrochromic
      iron(III)-complexed alginate hydrogel sensitive to bacterial metabolism, here
      applied to fast antibiotic-susceptibility determination. Bacteria under
      evaluation are entrapped -and pre-concentrated- in the hydrogel matrix by
      oxidation of iron (II) ions to iron (III) and in situ formation of the alginate
      hydrogel in less than 2min and in soft experimental conditions (i.e. room
      temperature, pH 7, aqueous solution). After incubation with the antibiotic
      (10min), ferricyanide is added to the biomaterial. Bacteria resistant to the
      antibiotic dose remain alive and reduce ferricyanide to ferrocyanide, which
      reacts with the iron (III) ions in the hydrogel to produce Prussian Blue
      molecules. For a bacterial concentration above 107 colony forming units per mL
      colour development is detectable with the bare eye in less than 20min. The
      simplicity, sensitivity, low-cost and short response time of the biomaterial and
      the assay envisages a high impact of these approaches on sensitive sectors such
      as public health system, food and beverage industries or environmental
      monitoring.

PMID- 29028578
TI  - Obstetric early warning score in Scandinavia. A survey of midwives' use of
      systematic monitoring in parturients.
AB  - OBJECTIVE: systematic monitoring has recently been implemented widely in non
      obstetric departments. In the UK, Early Warning Score (EWS) systems specifically
      designed for the obstetric population (OEWS) are used. No information on the use
      of OEWS in Scandinavia has been reported. Consequently, we wanted to investigate
      the use of vital signs and attitude towards systematic monitoring of parturients
      in Denmark, Norway and Sweden. DESIGN: electronic questionnaires sent to heads of
      midwifery. The heads of midwifery referred two clinically active midwives. All in
      hospital obstetric departments in Scandinavia were invited to participate.
      FINDINGS: heads of midwifery from 76 departments (68%), and 125 clinical midwives
      (82%) responded. Ten per cent of midwives reported use of OEWS. Reported
      implementation barriers to OEWS included lack of evidence and suspected impact on
      the parturient due to frequent interruptions. fifty-four per cent of clinical
      midwives reported a systolic blood pressure threshold of 90-139mmHg, while 33%
      reported a threshold of>160mmHg. Ninety-three per cent stated a low threshold for
      maternal heart rate<60 bpm whereas 10% reported an upper threshold heart rate >=
      150 bpm. Forty-seven per cent reported call for assistance thresholds for
      maternal heart rate at 60-110 bpm. KEY CONCLUSIONS: OEWS is not implemented in
      Scandinavian obstetric departments and reported thresholds of vital signs varied
      considerably. Major barriers for implementation in Scandinavia include midwives'
      concern of interruptions for the parturient and increased workload, and unclear
      benefit from use of OEWS. Local departments should provide midwives with
      unambiguous thresholds for vital signs in parturients either through local
      guidelines or via OEWS.

PMID- 29028579
TI  - The views of first time mothers completing an intervention to reduce postpartum
      weight retention: A qualitative evaluation of the mums OnLiNE study.
AB  - BACKGROUND: maternal postpartum weight retention (PPWR) has implications for
      short and long term weight-related health of both the mother and child. Little is
      known about how mothers perceive they may be best supported to achieve a healthy
      postpartum weight and healthy lifestyle behaviours. Evaluating existing
      postpartum weight focussed intervention strategies is an important step in the
      planning of future programs aimed at supporting new mothers. AIM: to describe the
      perspectives of women who completed the mums OnLiNE pilot intervention, regarding
      the acceptability and effectiveness of a program which aimed to limit PPWR and
      promote healthy diet and physical activity behaviours in new mothers. METHOD:
      descriptive qualitative research methods utilising semi-structured interview
      questions to explore new mothers' views regarding their participation in the mums
      OnLiNE intervention were used. All women who completed the intervention were
      invited to participate in one-on-one interviews via telephone. Interviews were
      digitally recorded and transcribed verbatim. Data were analysed utilising
      thematic analysis for common, emerging themes. FINDINGS: twelve women
      participated in the interviews. Six main themes including program usefulness,
      intervention components, walking, self-monitoring, barriers and challenges and
      future recommendations described women's views of the mums OnLiNE intervention.
      Women felt well supported being part of the program and their reported awareness
      of healthy eating increased. Telephone support was the most valued and helpful
      component of the intervention and the smartphone application for self-monitoring
      was used more often than the website. Walking was by far the most preferred
      activity as it was considered enjoyable and achievable and some reported that
      their incidental walking increased as a result of being part of the program. Lack
      of time and motivation were the main barriers to participation in the program.
      Suggestions for future programs included encouraging group support and mother
      baby exercise sessions. CONCLUSION: women perceived the mums OnLiNE intervention
      to be useful in promoting a healthy lifestyle and valued the support provided.
      Whilst barriers to participation in healthy lifestyle programs exist, well
      planned interventions which consider time constraints of new mothers, utilize one
      on-one support and offer social engagement with other new mothers may further
      support women in their attainment of healthy postpartum weight and lifestyle
      behaviours.

PMID- 29028581
TI  - Size-Controlled and Optical Properties of Platinum Nanoparticles by Gamma
      Radiolytic Synthesis.
AB  - Gamma radiolytic synthesis was used to produce size-controlled spherical platinum
      nanoparticles from an aqueous solution containing platinum tetraammine and
      polyvinyl pyrrolidone. The structural characterizations were performed using X
      ray diffraction, and transmission electron microscopy. The transmission electron
      microscopy was used to determine the average particle diameter, which decreased
      from 4.4nm at 80kGy to 2.8nm at 120kGy. The UV-visible absorption spectrum was
      measured and found that platinum nanoparticles exhibit two steady absorption
      maxima in UV regions due to plasmonic excitation of conduction electrons, which
      blue shifted to lower wavelengths with a decrease in particle size. We consider
      the conduction electrons of platinum nanoparticles to follow Thomas-Fermi-Dirac
      Weizsacker atomic model that they are not entirely free but weakly bounded to
      particles at lower-energy states {n = 5, l = 2 or 5d} and {n = 6, l = 0 or 6s},
      which upon receiving UV photon energy the electrons make intra-band quantum
      excitations to higher-energy states allowed by the principles of quantum number
      that results the absorption maxima. We found an excellent agreement between the
      experimental and theoretical results, which suggest that the optical absorption
      of metal nanoparticles could be fundamentally described by a quantum mechanical
      interpretation, which could be more relevant to photo-catalysis and heterogeneous
      catalysis.

PMID- 29028580
TI  - Revision of the Genus Micromonas Manton et Parke (Chlorophyta, Mamiellophyceae),
      of the Type Species M. pusilla (Butcher) Manton & Parke and of the Species M.
      commoda van Baren, Bachy and Worden and Description of Two New Species Based on
      the Genetic and Phenotypic Characterization of Cultured Isolates.
AB  - The green picoalgal genus Micromonas is broadly distributed in estuaries, coastal
      marine habitats and open oceans, from the equator to the poles. Phylogenetic,
      ecological and genomic analyses of culture strains and natural populations have
      suggested that this cosmopolitan genus is composed of several cryptic species
      corresponding to genetic lineages. We performed a detailed analysis of variations
      in morphology, pigment content, and sequences of the nuclear-encoded small
      subunit rRNA gene and the second internal transcribed spacer (ITS2) from strains
      isolated worldwide. A new morphological feature of the genus, the presence of tip
      hairs at the extremity of the hair point, was discovered and subtle differences
      in hair point length were detected between clades. Clear non-homoplasious
      synapomorphies were identified in the small-subunit rRNA gene and ITS2 spacer
      sequences of five genetic lineages. These findings lead us to provide emended
      descriptions of the genus Micromonas, of the type species M. pusilla, and of the
      recently described species M. commoda, as well as to describe 2 new species, M.
      bravo and M. polaris. By clarifying the status of the genetic lineages identified
      within Micromonas, these formal descriptions will facilitate further
      interpretations of large-scale analyses investigating ecological trends in time
      and space for this widespread picoplankter.

PMID- 29028582
TI  - Internalized stigma and its impact in Indian outpatients with bipolar disorder.
AB  - Patients with many psychiatric disorders have considerable internalized stigma.
      The current study intended to examine the level and impact of internalized stigma
      in patients with bipolar affective disorder (BPAD). 60 patients with BPAD, 33
      patients with schizophrenia and 30 patients with anxiety disorders were compared
      on Internalized Stigma of Mental Illness scale and The Stigma Scale. The patients
      with BPAD were assessed using Rosenberg Self-Esteem Scale (RSES), Participation
      scale (PS) and World Health Organization Quality Of Life - Brief Version - Hindi
      (WHOQOL-bref). Significant differences were found in all domains of self-stigma
      measures among the three groups. Using appropriate covariates, it was found that
      the differences were significant and independent of the effect of the covariates.
      In patients of BPAD, stigma and its domains were significantly correlated with
      the measures on monthly income, education, socio-occupational functioning, RSES,
      PS and WHOQOL-bref. Patients with BPAD experience substantial stigma, which was
      intermediate between that experienced by patients with schizophrenia (higher) and
      that experienced by patients with anxiety disorder (lower). Internalized stigma
      has significant impact on self-esteem, socio-occupational participation and
      functioning, and quality of life in patients with BPAD. Small sample size, sample
      of convenience, and cross-sectional design, limit the generalizability of the
      results.

PMID- 29028583
TI  - Influence of semantic consistency and perceptual features on visual attention
      during scene viewing in toddlers.
AB  - Conceptual representations of everyday scenes are built in interaction with
      visual environment and these representations guide our visual attention.
      Perceptual features and object-scene semantic consistency have been found to
      attract our attention during scene exploration. The present study examined how
      visual attention in 24-month-old toddlers is attracted by semantic violations and
      how perceptual features (i. e. saliency, centre distance, clutter and object
      size) and linguistic properties (i. e. object label frequency and label length)
      affect gaze distribution. We compared eye movements of 24-month-old toddlers and
      adults while exploring everyday scenes which either contained an inconsistent
      (e.g., soap on a breakfast table) or consistent (e.g., soap in a bathroom)
      object. Perceptual features such as saliency, centre distance and clutter of the
      scene affected looking times in the toddler group during the whole viewing time
      whereas looking times in adults were affected only by centre distance during the
      early viewing time. Adults looked longer to inconsistent than consistent objects
      either if the objects had a high or a low saliency. In contrast, toddlers
      presented semantic consistency effect only when objects were highly salient.
      Additionally, toddlers with lower vocabulary skills looked longer to inconsistent
      objects while toddlers with higher vocabulary skills look equally long to both
      consistent and inconsistent objects. Our results indicate that 24-month-old
      children use scene context to guide visual attention when exploring the visual
      environment. However, perceptual features have a stronger influence in eye
      movement guidance in toddlers than in adults. Our results also indicate that
      language skills influence cognitive but not perceptual guidance of eye movements
      during scene perception in toddlers.

PMID- 29028584
TI  - Diagnosis and treatment options for sequelae following radiation treatment of
      brain tumors.
AB  - Radiation serves an important role in the treatment of metastatic and primary
      brain tumors. Radiation carries a risk of post radiation treatment effects, such
      as pseudoprogression and radiation necrosis. The ability to differentiate between
      radiation necrosis, pseudoprogression, and tumor recurrence remains a diagnostic
      conundrum with varying treatment options. In this review, we will discuss the
      pathophysiology, diagnostic imaging modalities, and treatments of these post
      radiation treatment effects. We focus on the latest developments in magnetic
      resonance imaging (MRI) modalities including imaging biomarkers and the newest
      therapeutics such as VEGF inhibitors, Hyperbaric Oxygen Therapy, sensitized
      cytotoxic T cells, and Laser Interstitial Thermal Therapy (LITT).

PMID- 29028585
TI  - Seeing odors in color: Cross-modal associations in children and adults from two
      cultural environments.
AB  - We investigated the occurrence and underlying processes of odor-color
      associations in French and American 6- to 10-year-old children (n = 386) and
      adults (n = 137). Nine odorants were chosen according to their familiarity to
      either cultural group. Participants matched each odor with a color, gave hedonic
      and familiarity judgments, and identified each odor. By 6 years of age, children
      displayed culture-specific odor-color associations, but age differences were
      noted in the type of associations. Children and adults in both cultural groups
      shared common associations and formed associations that were unique to their
      environment, underscoring the importance of exposure learning in odor-color
      associations.

PMID- 29028586
TI  - Ameliorative effect of borneol, a natural bicyclic monoterpene against
      hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced
      diabetic Wistar rats.
AB  - Diabetes mellitus is a major public health problem worldwide. Oxidative stress
      plays a pivotal role in the pathogenesis of diabetes as it is one of the
      inevitable outcomes of the cellular process. The present study aims to
      investigate the putative antihyperglycemic, antihyperlipidemic and antioxidant
      efficacy of a monoterpene borneol, in comparison with glibenclamide, a standard
      drug for therapy of diabetes. Diabetes was induced by a single intraperitoneal
      injection of 40mg/kg body weight. The results of the present study showed a
      significant increase in the biochemical indices viz., fasting blood glucose
      concentration, glycated hemoglobin, urea, alanine aminotransferase, aspartate
      aminotransferase, malondialdehyde concentration, total cholesterol,
      triglycerides, low-density lipoprotein cholesterol, very low-density lipoprotein
      cholesterol and atherogenic index, with a significant decrease in body weight,
      plasma insulin, HOMA-beta-cell functioning index, glycogen, high-density
      lipoprotein cholesterol and antioxidant enzyme activities, viz., superoxide
      dismutase, catalase and reduced glutathione in diabetic rats when compared to
      controls. In addition, histology of the normal architecture of pancreas was
      affected in diabetic rats when compared to controls. The results for the first
      time reveal that oral administration of borneol for twenty eight days
      significantly attenuated the above mentioned alterations near to controls.
      Therefore, it is suggested that borneol could be a potential therapeutic
      antidiabetic molecule of biological relevance.

PMID- 29028587
TI  - Chemical constituents and medical benefits of Plantago major.
AB  - The medicinal benefits of Plantago major have been acknowledged around the world
      for hundreds of years. This plant contains a number of effective chemical
      constituents including flavonoids, alkaloids, terpenoids, phenolic acid
      derivatives, iridoid glycosides, fatty acids, polysaccharides and vitamins which
      contribute to its exerting specific therapeutic effects. Correspondingly, studies
      have found that Plantago major is effective as a wound healer, as well as an
      antiulcerative, antidiabetic, antidiarrhoeal, anti-inflammatory, antinociceptive,
      antibacterial, and antiviral agent. It also combats fatigue and cancer, is an
      antioxidant and a free radical scavenger. This paper provides a review of the
      medicinal benefits and chemical constituents of Plantago major published in
      journals from year 1937 to 2015 which are available from PubMed, ScienceDirect
      and Google Scholar.

PMID- 29028588
TI  - Formation of struvite urinary stones and approaches towards the inhibition-A
      review.
AB  - BACKGROUND: Struvite is one of the most common urinary/kidney stones, composed of
      magnesium ammonium phosphate (MgNHPO4.H2O). They are also termed as infection
      stones as these are associated with urinary tract infections. Numerous studies
      have been carried out to examine the growth and inhibition of struvite stones.
      OBJECTIVE: This review summarizes various reports on the factors responsible for
      inducing struvite stones in the kidney and gives a detailed account of studies on
      inhibition of growth of struvite crystals. RESULTS: The presence of urea
      splitting bacteria such as Proteus mirabilis and alkaline pH plays a crucial role
      in struvite formation. In vitro inhibition of struvite stones by various chemical
      agents were examined mainly in artificial urine whereas inhibition by herbal
      extracts was studied in vitro by gel diffusion technique. Herbal extracts of
      curcumin, Boerhaavia diffusa Linn, Rotula aquatica and many other plants, as well
      as some chemicals like pyrophosphate, acetohydroxamic acid, disodium EDTA and
      trisodium citrate, were reported to successfully inhibit struvite formation.
      CONCLUSION: The present review recapitulates various factors affecting the growth
      of struvite urinary stones and the inhibitory role of certain chemicals and
      herbal extracts. Most of the tested plants are edible hence can be easily
      consumed without any adverse effects whereas the side effects of chemicals are
      unknown due to lack of toxicity studies. Thus, the use of herbal extracts might
      serve as an alternate and safe therapy for prevention of struvite stones.

PMID- 29028589
TI  - TanshinoneIIA enhances the chemosensitivity of breast cancer cells to doxorubicin
      through down-regulating the expression of MDR-related ABC transporters.
AB  - As the first-line drug for breast cancer chemotherapy, doxorubicin (Dox) has
      strong cardiotoxicity. Meanwhile, prolonged Dox treatment of patients with breast
      cancer may result in resistance of breast cancer cells to Dox and an increased
      number of Dox-resistant breast cancer stem cells (BCSCs), thereby easily leading
      to breast cancer relapse. TanshinoneIIA (Tan IIA) has anti-tumor activity in
      addition to its cardiovascular protective effect. By preparing Dox resistant
      human breast cancer MCF-7 cells, here, we wanted to assess a new use of Tan IIA
      in enhancing the chemosensitivity of breast cancer cells to Dox and investigated
      its possible mechanisms. The results showed that Tan IIA could enhance the anti
      tumor effect of Dox on MCF-7 and MCF-7/dox cells in a dose-dependent manner,
      especially that of on MCF-7/dox cells. Even nontoxic dose of Tan IIA could also
      promote intracellular Dox accumulation of MCF-7 and MCF-7/dox cells through down
      regulating the expression of efflux ABC transporters including P-gp, BCRP and
      MRP1, which can effectively eliminated cancerous cells including BCSCs, thereby
      enhancing the chemosensitivity of breast cancer. Therefore, Tan IIA can be used
      as a new potential chemotherapeutic sensitizer for the combination treatment of
      breast cancer.

PMID- 29028590
TI  - Efficacy and tolerability of lisdexamfetamine as an antidepressant augmentation
      strategy: A meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Psychostimulants have been used in the treatment of depression, with
      mixed results. This meta-analysis examines the efficacy and tolerability of the
      stimulant Lisdexamfetamine (LDX) as an add-on strategy in those with MDD who have
      failed to respond to an antidepressant. METHOD: Randomized control trials were
      identified and extracted from Pubmed; Web of Science; PsychINFO; and Cochrane
      Library. The efficacy of LDX was evaluated using Hedges' g and Odds Ratio,
      whereas Risk Difference was used to assess the safety and tolerability of LDX.
      RESULTS: Four studies met inclusion criteria. LDX did not demonstrate superiority
      in efficacy relative to placebo as indicated by a Hedges' g score of 0.126 (95%
      CI -0.040-0.291; p = 0.136) for mean change in Montgomery-Asberg Depression
      Rating Scale. Odds ratios of 1.206 (95% CI 0.745-1.954; p = 0.446) and 1.244 (95%
      CI 0.959-1.614; p = 0.1) were found for remission and response rates
      respectively. Risk differences of -0.1 (95% CI -0.155-(-0.045); p < 0.001)
      indicated a 10% increase chance of developing treatment-emergent adverse events
      (TEAE) in the LDX group. There was no significant difference in risk for
      developing serious or severe TEAE and discontinuing treatment due to TEAE.
      LIMITATIONS: The number of included studies was small and only one metric was
      available for analysis of antidepressant efficacy of LDX. CONCLUSIONS: LDX when
      used as antidepressant augmentation produced a small effect in improving
      depressive symptoms that approached trend-level significance and demonstrated
      comparable tolerability to placebo. Further studies are needed to determine the
      optimal clinical subset of depressive symptoms responsive to LDX augmentation.

PMID- 29028591
TI  - Posttraumatic stress disorder symptoms in parents and adolescents after the
      Wenchuan earthquake: A longitudinal actor-partner interdependence model.
AB  - BACKGROUND: Previous research has examined the association between parents' and
      children's posttraumatic stress disorder symptoms (PTSS) after a variety of
      traumatic events. However, longitudinal parent-child dyadic studies are scarce.
      METHODS: Independent self-reports were collected from parent-adolescent dyads (n
      = 688) after the 2008 Wenchuan earthquake. Adolescents (Mean = 15.22 years;
      61.63% female) and one of their parents (Mean = 41.04 years; 58.14% female) each
      reported on their PTSS at 12 (T12m) and 18 months (T18m) following the
      earthquake. Longitudinal actor-partner interdependence models (APIMs) were used
      to examine PTSS within dyads. RESULTS: The prevalence rates of probable PTSD at
      T12m and T18m were 18.90% and 11.92% in adolescents; as well as 22.09% and 15.12%
      in parents, showing a significant decline over time. After adjusted for
      earthquake exposure, both maternal and paternal PTSS at T12m prospectively
      predicted adolescent girls' and boys' PTSS at T18m (mother to daughter: beta =
      0.13; mother to son: beta = 0.17; father to daughter: beta = 0.17; father to son:
      beta = 0.33), while adolescent girls' and boys' PTSS at T12m only predicted
      maternal PTSS at T18m (daughter to mother: beta = 0.20; son to mother: beta =
      0.20), but not paternal PTSS at T18m. LIMITATIONS: Self-reported measures other
      than clinical reviews were used to collect data. CONCLUSIONS: This study
      highlights the mutual impacts of adolescent and parental (especially maternal)
      PTSS after a disaster. Psychological prevention and intervention for adolescent
      disaster survivors should adopt a whole family approach.

PMID- 29028592
TI  - Elevation of plasma neutrophil gelatinase-associated lipocalin (NGAL) levels in
      schizophrenia patients.
AB  - BACKGROUND: Psychiatric diseases are usually accompanied by immune dysregulation
      and activation of the inflammatory response system. However, the characteristics
      of immunoinflammatory markers in psychiatric diseases are not well defined.
      METHODS: Seventy-three patients with psychiatric diseases were divided into four
      groups, including a schizophrenia group, an anxiety disorder group, a unipolar
      depression group, and a bipolar disorder group, according to the ICD-10 and DSM
      IV codes. Neutrophil gelatinase-associated lipocalin (NGAL) and associated
      classical immunoinflammatory markers including C-reactive protein (CRP), Th1/Th2
      cytokines (IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma), total leukocyte
      count (TLC), and neutrophilic granulocyte percentage (NEU%) were analysed;
      patients with physical diseases were excluded to avoid confounders. Fifteen
      healthy, age- and gender-matched individuals served as controls. RESULTS:
      Compared with the corresponding values in the control group, the level of CRP in
      each psychiatric disease group, the levels of IFN-gamma and NGAL in the
      schizophrenia group, and the NEU% in the depression group were significantly
      elevated (P < 0.05). Compared with the levels in the schizophrenia group, the
      levels of CRP in the bipolar disorder and depression groups, the level of IFN
      gamma in the bipolar disorder group, and the levels of NGAL in the anxiety
      disorder and depression groups were significantly decreased (P < 0.05). Compared
      with the depression group, the bipolar disorder group showed significant
      elevation the NGAL level. LIMITATION: The sample size was relatively small.
      CONCLUSIONS: Immunoinflammatory markers were elevated in patients with
      psychiatric diseases, especially schizophrenia. We are the first to report that
      the level of NGAL is significantly increased in schizophrenia patients.

PMID- 29028593
TI  - Genetic variations in the p11/tPA/BDNF pathway are associated with post stroke
      depression.
AB  - BACKGROUND: The effects of BDNF on post stroke depression (PSD) may be influenced
      by genetic variations in intracellular signal transduction pathways, such as the
      p11/tPA/BDNF pathway. In this study, we aimed to determine the association of
      polymorphisms in candidate genes of the gene transduction pathway with PSD, as
      well as the effects of the interactions between genes in our Chinese sample.
      METHODS: Two-hundred-fifty-four Chinese samples with acute ischaemic stroke
      included 122 PSD patients and 132 nonPSD patients. Sixty-five single nucleotide
      polymorphisms (SNPs) in six genes (p11, tPA, PAI-1, BDNF, TrkB and p75NTR) of the
      p11/tPA/BDNF pathway with minor allele frequencies > 5% were successfully
      genotyped from an initial series of 76 SNPs. The severity of depressive symptoms
      was assessed by the 17-item Hamilton Depression Rating scale score. Environmental
      factors were measured with the life events scale and social support rating scale
      for all patients. SNP and haplotype associations were analysed using gPLINK
      software. Gene-gene interactions were evaluated with generalized multifactor
      dimensionality reduction software. RESULTS: The results showed that TrkB
      polymorphisms (rs11140793AC genotype, rs7047042CG genotype, rs1221CT genotype,
      rs2277193TC genotype and rs2277192AG genotype) were significantly associated with
      PSD. Three haplotypes (AT, GG, and AAT) of TrkB were significantly associated
      with PSD. Seven haplotypes (GC, AG, ACG, CGC, GCT, ACGC and ACAT) of BDNF were
      significantly correlated with PSD. We identified significant gene-gene
      interactions between the p11 (rs11204922 SNP), tPA (rs8178895, rs2020918 SNPs)
      and BDNF (rs6265, rs2049046, rs16917271, rs727155 SNPs) genes in the PSD group.
      We also identified significant gene-gene interactions between the BDNF
      (rs2049046, rs7931247 SNPs) and TrkB (rs7816 SNP) genes with increased occurrence
      of PSD and sig gene-gene interactions between the BDNF gene (rs6265, rs56164415,
      rs2049046, rs4923468, rs2883187, rs16917271, rs1491850, rs727155, rs2049048 SNPs)
      and p75NTR gene (rs2072446, rs11466155) in the PSD group. CONCLUSION: These
      findings provides evidence that the TrkB gene, BDNF and TrkB haplotypes, and gene
      gene interactions between p11, tPA and BDNF are all associated with PSD, which
      suggests that genetic variations in the p11/tPA/BDNF pathway may play a central
      role in regulating the underlying mechanism of PSD.

PMID- 29028594
TI  - Observation of intra- and interspecific differences in the nest chemical profiles
      of social wasps (Hymenoptera: Polistinae) using infrared photoacoustic
      spectroscopy.
AB  - The aim of this study was to explore whether the nest chemical profile (NCP) can
      be used to determine intra- and interspecific differences in social wasps of the
      subfamily Polistinae. For this purpose, Fourier transform infrared photoacoustic
      spectroscopy (FTIR-PAS) was used to directly analyze small pieces of nest as well
      as the gasters of females. An advantage of the methodology was that no sample
      preparation was required. FTIR-PAS combined with multivariate discriminant
      analyzes was used, to the best of our knowledge for the first time, to evaluate
      the NCPs of six species of polistine wasps, observing the influence of the
      nesting environment and investigating the relationships among the nest and female
      cuticular chemical profiles. The results revealed significant inter-species
      differences among the NCPs, as well as strong correlations with the environments
      in which the nests were located. The Mischocyttarus and Polistes species belong
      to the same tribe (Polistini) and therefore exhibited similar NCPs. These species
      were separated from the Polybia species in the NCP dendrogram, mainly because the
      Polybia belong to another tribe (Epiponini). Correlation was observed between the
      NCPs and the cuticular chemical profiles of females. The findings of the study
      demonstrated the importance of the NCP for differentiation of species and
      environments, and the utility of FTIR-PAS for identification of correlations
      between individuals and nests. The results confirmed the hypothesis that the NCP
      can be used as an additional tool for intra- and interspecific differentiation in
      social wasps of the subfamily Polistinae.

PMID- 29028595
TI  - "Loser" or "Popular"?: Neural response to social status words in adolescents with
      major depressive disorder.
AB  - Concerns about social status are ubiquitous during adolescence, with information
      about social status often conveyed in text formats. Depressed adolescents may
      show alterations in the functioning of neural systems supporting processing of
      social status information. We examined whether depressed youth exhibited altered
      neural activation to social status words in temporal and prefrontal cortical
      regions thought to be involved in social cognitive processing, and whether this
      response was associated with development. Forty-nine adolescents (ages 10-18; 35
      female), including 20 with major depressive disorder and 29 controls, were
      scanned while identifying the valence of words that connoted positive and
      negative social status. Results indicated that depressed youth showed reduced
      late activation to social status (vs neutral) words in the superior temporal
      cortex (STC) and medial prefrontal cortex (MPFC); whereas healthy youth did not
      show any significant differences between word types. Depressed youth also showed
      reduced late activation in the dorsolateral prefrontal cortex and fusiform gyrus
      to negative (vs positive) social status words; whereas healthy youth showed the
      opposite pattern. Finally, age was positively associated with MPFC activation to
      social status words. Findings suggest that hypoactivation in the "social
      cognitive brain network" might be implicated in altered interpersonal functioning
      in adolescent depression.

PMID- 29028597
TI  - A continuum model for tension-compression asymmetry in skeletal muscle.
AB  - Experiments on passive skeletal muscle on different species show a strong
      asymmetry in the observed tension-compression mechanical behavior. This asymmetry
      shows that the tension modulus is two orders of magnitude higher than the
      compression modulus. Until now, traditional analytical constitutive models have
      been unable to capture that strong asymmetry in anisotropic solids using the same
      material parameters. In this work we present a model which is able to accurately
      capture five experimental tests in chicken pectoralis muscle, including the
      observed tension-compression asymmetry. However, aspects of the anisotropy of the
      tissue are not captured by the model.

PMID- 29028596
TI  - Synthesis, characterization and evaluation of a fluorinated resin monomer with
      low water sorption.
AB  - A fluorinated acrylate monomer (4-TF-PQEA) without BPA (bisphenol-A) structure
      was synthesized and mixed with triethylene glycol dimethacrylate (TEGDMA) to used
      as dental resin system in order to achieve lower water sorption and reduce human
      exposure to BPA derivatives. Double bond conversion (DC) was measured using
      Fourier transform infrared spectroscopy (FTIR). Water sorption (WS), water
      solution (WL) and depth of cure (DOC) were evaluated according to ISO 4049:2009.
      Water contact angle (CA) was measured using contact angle analyzer.
      Polymerization shrinkage (PS) was evaluated according to the Archimedes'
      principle and ISO 17304:2013. Flexural strength (FS) and flexural modulus (FM)
      were measured by three-point bending test with a universal testing machine
      according to ISO 4049:2009. Comprehensive strength (CS) and vickers microhardness
      (VM) were also investigated. Thermal stability test was measure by
      Thermogravimetric analyzer. Cytotoxicity of three resin systems was tested
      through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid)
      cytotoxicity method according to the ISO 10993-5:2009. Bisphenol-A glycidyl
      dimethacrylate (Bis-GMA)/ TEGDMA resin system was used as a control. The results
      show that 4-TF-PQEA/TEGDMA resin system had lower PS, lower WS and higher DC
      values than those of Bis-GMA/TEGDMA resin system except some mechanical
      properties, such as FS, FM and CS. Moreover, properties of other 4-TF-PQEA
      containing resin systems were also comparable with those of Bis-GMA/TEGDMA resin
      system. In particular, the overall performance of resin system consisted of 4-TF
      PQEA/Bis-GMA/TEGDMA is optimized when the mixture ratio is 30/40/30(wt/wt/wt).
      Therefore, the 4-TF-PQEA has potential to be used as resin monomer for dental
      resin composites to achieve lower water sorption.

PMID- 29028598
TI  - A particle swarm-based algorithm for optimization of multi-layered and graded
      dental ceramics.
AB  - The thermal residual stresses (TRSs) generated owing to the cooling down from the
      processing temperature in layered ceramic systems can lead to crack formation as
      well as influence the bending stress distribution and the strength of the
      structure. The purpose of this study is to minimize the thermal residual and
      bending stresses in dental ceramics to enhance their strength as well as to
      prevent the structure failure. Analytical parametric models are developed to
      evaluate thermal residual stresses in zirconia-porcelain multi-layered and graded
      discs and to simulate the piston-on-ring test. To identify optimal designs of
      zirconia-based dental restorations, a particle swarm optimizer is also developed.
      The thickness of each interlayer and compositional distribution are referred to
      as design variables. The effect of layers number constituting the interlayer
      between two based materials on the performance of graded prosthetic systems is
      also investigated. The developed methodology is validated against results
      available in literature and a finite element model constructed in the present
      study. Three different cases are considered to determine the optimal design of
      graded prosthesis based on minimizing (a) TRSs; (b) bending stresses; and (c)
      both TRS and bending stresses. It is demonstrated that each layer thickness and
      composition profile have important contributions into the resulting stress field
      and magnitude.

PMID- 29028599
TI  - Predicting the weathering of fuel and oil spills: A diffusion-limited evaporation
      model.
AB  - The majority of the evaporation models currently available in the literature for
      the prediction of oil spill weathering do not take into account diffusion-limited
      mass transport and the formation of a concentration gradient in the oil phase.
      The altered surface concentration of the spill caused by diffusion-limited
      transport leads to a slower evaporation rate compared to the predictions of
      diffusion-agnostic evaporation models. The model presented in this study
      incorporates a diffusive layer in the oil phase and predicts the diffusion
      limited evaporation rate. The information required is the composition of the
      fluid from gas chromatography or alternatively the distillation data. If the
      density or a single viscosity measurement is available the accuracy of the
      predictions is higher. Environmental conditions such as water temperature, air
      pressure and wind velocity are taken into account. The model was tested with
      synthetic mixtures, petroleum fuels and crude oils with initial viscosities
      ranging from 2 to 13,000 cSt. The tested temperatures varied from 0  degrees C to
      23.4  degrees C and wind velocities from 0.3 to 3.8 m/s. The average absolute
      deviation (AAD) of the diffusion-limited model ranged between 1.62% and 24.87%.
      In comparison, the AAD of a diffusion-agnostic model ranged between 2.34% and
      136.62% against the same tested fluids.

PMID- 29028600
TI  - Physico-chemical characterization of playground sand dust, inhalable and
      bioaccessible fractions.
AB  - Dust is a mixture of natural and anthropogenic particles originated from multiple
      sources, which can represent an hazard for human health. Playgrounds are a site
      of particularly concern, due to sand dust ingestion by toddlers and inhalation.
      In this study, 37 sands used in public playgrounds in the city of Barcelona were
      physico-chemically characterized also in relation to routine maintenance
      activities such as disinfection and sand renewal. The analyzed sands show a
      felsic mineralogy dominated by Na-feldspar, quartz, and, to a lesser extent, K
      feldspar, with minor amounts of clay minerals, carbonates and hematite. Particle
      fractions below 10, 2.5 and 1 MUm represent, on average, 0.65%, 0.17% and 0.07%
      of bulk volume, respectively, although, due to the human grinding, these initial
      fractions increased every year by a 18%, 5% and 2% respectively. Disinfection of
      sands effectively reduced only the NH4+ concentration, among inorganic species.
      The average metal content was anthropogenically enriched, with respect to the
      upper continental crust, only for Sb and As. Both elements show high spatial
      variation indicating local sources such as road traffic for Sb (contributing
      mostly to the total concentration), and industry for As (also contributing with
      highly bioaccessible Sb, Cu and Zn). A clear inverse relationship between total
      concentrations of some elements and their leachable (Sb) and bioaccessible (Sb
      and Cr) fractions is observed. The most bioaccessible elements were Ca > Ni > Cu
      > Sr > Cd > Pb, all above the 25% of the total concentration. Bioaccessibility
      was higher for the carbonate-bearing particles and for the anthropic emitted
      metals (>50% of Ba, Cu, K, Pb and Zn).

PMID- 29028601
TI  - Developing predictive models for toxicity of organic chemicals to green algae
      based on mode of action.
AB  - Organic chemicals in the aquatic ecosystem may inhibit algae growth and
      subsequently lead to the decline of primary productivity. Growth inhibition tests
      are required for ecotoxicological assessments for regulatory purposes. In silico
      study is playing an important role in replacing or reducing animal tests and
      decreasing experimental expense due to its efficiency. In this work, a series of
      theoretical models was developed for predicting algal growth inhibition (log
      EC50) after 72 h exposure to diverse chemicals. In total 348 organic compounds
      were classified into five modes of toxic action using the Verhaar Scheme. Each
      model was established by using molecular descriptors that characterize electronic
      and structural properties. The external validation and leave-one-out cross
      validation proved the statistical robustness of the derived models. Thus they can
      be used to predict log EC50 values of chemicals that lack authorized algal growth
      inhibition values (72 h). This work systematically studied algal growth
      inhibition according to toxic modes and the developed model suite covers all five
      toxic modes. The outcome of this research will promote toxic mechanism analysis
      and be made applicable to structural diversity.

PMID- 29028602
TI  - Toxicity of ZnO nanoparticles (NPs) to A549 cells and A549 epithelium in vitro:
      Interactions with dipalmitoyl phosphatidylcholine (DPPC).
AB  - Once inhaled, nanoparticles (NPs) will first interact with lung surfactant
      system, which may influence the colloidal aspects of NPs and consequently the
      toxic potential of NPs to pulmonary cells. In this study, we investigated the
      effects of dipalmitoyl phosphatidylcholine (DPPC), the major component in lung
      surfactant, on stability and toxicity of ZnO NPs. The presence of DPPC increased
      the UV-vis spectra, hydrodynamic size, Zeta potential and dissolution rate of ZnO
      NPs, which indicates that DPPC might interact with NPs and affect the colloidal
      stability of NPs. Exposure to ZnO NPs induced cytotoxicity associated with
      increased intracellular Zn ions but not superoxide in A549 cells. In A549
      epithelium model, exposure to ZnO NPs induced cytotoxicity and decreased the
      release of interleukin 6 (IL-6) without a significant effect on epithelial
      permeability rate. Co-exposure of A549 cells or A549 epithelium model to DPPC and
      ZnO NPs induced a higher release of lactate dehydrogenase (LDH) and interleukin-6
      (IL-6) compared with the exposure of ZnO NPs alone. We concluded that the
      presence of DPPC could influence the colloidal stability of ZnO NPs and increase
      the damage of NPs to membrane probably due to the increased positive surface
      charge.

PMID- 29028603
TI  - A surface-confined DNA assembly amplification strategy on DNA nanostructural
      scaffold for electrochemiluminescence biosensing.
AB  - A critical challenge in surface-based DNA assembly amplification is the reduced
      accessibility of DNA strands arranged on a heterogeneous surface compared to that
      in homogeneous solution. Here, a novel in situ surface-confined DNA assembly
      amplification electrochemiluminescence (ECL) biosensor based on DNA
      nanostructural scaffold was presented. In this design, a stem-loop structural DNA
      segment (Hairpin 1) was constructed on the vertex of DNA nanostructural scaffold
      as recognition probe. In the present of target DNA, the hairpin structure changed
      to rod-like through complementary hybridization with target DNA, resulting in the
      formation of Hairpin 1:target DNA. When the obtained Hairpin 1:target DNA met
      Hairpin 2 labeled with glucose oxidase (GOD), the DNA cyclic amplification was
      activated, releasing target DNA into homogeneous solution for the next recycling.
      Thus, the ECL signal of Ru(bpy)32+-TPrA system was quenched by H2O2, the product
      of GOD catalyzing glucose. As a result, this proposed method achieved a linear
      range response from 50 aM to 10 pM with lower detection limit of 20 aM.

PMID- 29028604
TI  - New zinc(II) N4 tetradentate Schiff base complex: A potential cytotoxic
      metallodrug and simple precursor for the preparation of ZnO nanoparticles.
AB  - A novel Schiff base Zn(II) complex using a tetradentate Schiff base ligand was
      synthesized and characterized. The results of cytotoxicity assay revealed that
      the prepared complex induced cytotoxicity in a breast cancer cell line. Thus, the
      binding of the Zn(II) complex to human serum albumin (HSA) was investigated using
      spectroscopic and molecular docking methods. The fluorescence data showed that
      the Zn(II) complex quenched protein fluorescence by a static quenching mechanism.
      The binding constant (Kb), number of binding sites (n), and thermodynamic
      parameters were calculated and showed that the Zn(II) complex binds to HSA
      through hydrogen bond and Vander Waals interactions with one binding site.
      Protein-ligand docking analysis confirmed that the Zn(II) complex binds to
      residues located in the subdomain IIA of HSA. This Zn(II) complex was used for
      the preparation of ZnO nanoparticles, and their photocatalytic activities were
      examined via photocatalytic degradation of ethidium bromide (EBr) in the absence
      of UV-vis irradiation. The results showed that these nanoparticles are promising
      materials for photocatalytic degradation.

PMID- 29028605
TI  - The construction and characterization of hybrid paclitaxel-in-micelle-in-liposome
      systems for enhanced oral drug delivery.
AB  - In this study, novel paclitaxel (PTX) loaded hybrid liposomes for oral PTX
      delivery were prepared through incorporating PTX loaded polyion complex micelles
      comprised of positively charged Pluronic F127-Polyethylenimine (PF127-PEI)
      copolymer and negatively charged sodium cholate (CA) into liposomes consisted of
      phospholipid molecules. According to the results, this kind of PTX-loaded hybrid
      liposomes showed improved PTX encapsulation efficiency, sustained PTX release,
      and enhanced PTX absorption in intestine. The mechanism for enhancing absorption
      was demonstrated in connection with inhibition of the efflux mediated by
      multidrug resistance protein, intestinal P-gp. In pharmacokinetic study, the
      absolute oral bioavailability of PTX loaded in hybrid liposomes had reached to
      37.91%. All of these results demonstrated that the application of this novel PTX
      loaded hybrid liposomes is a strategy with great potential for highly effective
      oral PTX delivery.

PMID- 29028606
TI  - Inflammatory and biocompatibility evaluation of antimicrobial peptide GL13K
      immobilized onto titanium by silanization.
AB  - The inflammatory reaction around the implant after implant placement is important
      not only for osseointegration but also for long-term implant survivals. In our
      study, GL13K, an antimicrobial peptide, was immobilized onto titanium surfaces to
      improve its anti-inflammatory properties. The method of silanization was used to
      immobilize the GL13K, which was confirmed by X-ray photoelectron spectroscopy,
      scanning electron microscopy, atomic force microscopy, water contact angle
      measurement. DAPI fluorescence staining and Cell Counting Kit-8 (CCK-8) were used
      to measure the cell attachment and cell viability of the RAW264.7, which
      indicated a good cytocompatibility. Cellular morphology of RAW264.7 on modified
      surfaces showed less cell pseudopod. ELISA and qRT-PCR were performed to measure
      the inflammatory activity of the modified titanium surfaces. The secretion levels
      of pro-inflammatory cytokines interleukin (IL)-1beta, tumor necrosis factor-alpha
      (TNF-alpha) and inducible nitric oxide synthase (iNOS) were downregulated at 12h,
      24h, and 48h, while the anti-inflammatory cytokines IL-10 and arginase were
      upregulated at 12h, 24h, and 48h. All results indicate that the GL13K-coated
      titanium surfaces make the inflammatory process towards a less pro-inflammatory,
      which may promote the process of osseointegration.

PMID- 29028607
TI  - pH-Induced interfacial properties of Chaplin E from Streptomyces coelicolor.
AB  - Chaplin E, or Chp E, is a surface active peptide secreted by Streptomyces
      coelicolor that adopts different structures depending on solution pH but the
      effect of these structures on the interfacial properties of Chp E is not known.
      In experiments paired with simulations, Chp E was found to display pH-dependent
      interfacial assembly and surface activity. At pH 3.0, Chp E formed an ordered non
      amyloidal interfacial film with high surface activity; while at pH 10.0, Chp E
      self-assembled into a heterogeneous film containing randomly arranged fibrils at
      the interface that was less surface active compared to the film formed at pH 3.0.
      In simulations at pH 10.0, Chp E molecules showed a higher propensity for
      dimerization within the solution phase, lower rate of adsorption to the interface
      and tighter inter-molecular associations at the interface, consistent with the
      lower surface activity and smaller interfacial area coverage per molecule
      measured at this pH compared to at pH 3.0. A model is presented for the role of
      Chp E in the developmental differentiation of Streptomyces coelicolor, where Chp
      E contributes to changes in surface tension at low pH and the formation of
      fibrils on the surface of aerial hyphae at high pH. Our data also suggest Chp E
      could be a promising surface active agent with functional activity that can be
      controlled by pH.

PMID- 29028608
TI  - Establishment of nerve growth factor gradients on aligned chitosan-polylactide
      /alginate fibers for neural tissue engineering applications.
AB  - Nerve conduits containing aligned fibrous fillers with gradiently distributed
      signal molecules are essential for long-gap nerve repair. This study was to
      develop an approach for establishing nerve growth factor (NGF) gradients onto the
      aligned chitosan-polylactide (CH-PLA) fibers. CH-PLA containing 37wt% of PLA was
      spun into fibers using a wet-spinning technique. CH-PLA fibers showed much higher
      wet-state tensile strength, enhanced degradation tolerance and significantly
      lower swelling degree in comparison to chitosan fibers. The CH-PLA fibers with
      diameters from 40 to 60MUm were selected and segmentally coated in bundles using
      NGF-contained alginate solutions to establish NGF gradients lengthwise along
      fibers. The diameter of resulting NGF-loaded CH-PLA/alginate fibers was well
      controlled within a range between 60 and 120MUm. Calcium ion crosslinked alginate
      coating layers on fibers showed abilities to administer the sustainable NGF
      release in a gradient distribution manner for at least 5 weeks. NGF-induced
      neurite outgrowth of PC12 cells confirmed that bioactivity of NGF released from
      fibers was well retained.

PMID- 29028609
TI  - Daunorubicin and doxorubicin molecular interplay with 2D membrane models.
AB  - The anthracyclines daunorubicin and doxorubicin are widely used antineoplastic
      agents due to their therapeutic activity against a broad variety of human
      cancers. Although, the classical model to explain anthracyclines' cytotoxicity
      has been based in the direct interference with nucleic acid function, evidence
      suggests that the plasma membrane is also involved in the drug's mechanism of
      action. In this work, the interaction of these drugs with two-dimensional
      membrane models were studied in order to gain further insights at the molecular
      level regarding anthracyclines membrane interactions. For that purpose, Langmuir
      monolayers composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC),
      sphingomyelin (SM) and cholesterol (Chol) were used, since these are the most
      common lipids found in biological membranes. Several biophysical techniques were
      employed: surface pressure (pi) - area (A) isotherms measurements were used to
      investigate the adsorption and penetration of drugs, polarization-modulation
      infrared reflection-absorption spectroscopy (PM-IRRAS) to acquire structural
      information and Brewster angle microscopy (BAM) to record images of the
      monolayers on the micrometer scale. The interactions of anthracyclines were
      assessed by alterations in the monolayers' shape, characteristic parameters (Cs-1
      values and area per lipid molecule at 30mN.m-1 and under maximum packing
      conditions) and morphology of each 2D model studied. The presence of the drugs in
      the interface led to the production of less ordered monolayers, as evidenced by
      the decrease in the compressibility modulus. In addition, the drugs' effect on
      the membrane organization is related with their chemical structure and depends on
      the membranes phase. For lower surface pressures, both electrostatic and
      hydrophobic interactions led to significant modifications in the monolayer order.
      With further compression, the impact of such interactions is reduced, resulting
      in the squeezing-out of some drug molecules from the interface. Furthermore, BAM
      images showed a clear anticancer drug interplay with the lipid monolayer by
      changes in the domains shape and appearance of bright dots, which are located in
      the frontier between the condensed and expanded lipid phases.

PMID- 29028610
TI  - Systematic review and meta-analysis of dropout rates in individual psychotherapy
      for generalized anxiety disorder.
AB  - BACKGROUND: Despite being a relatively prevalent and debilitating disorder,
      Generalized Anxiety Disorder (GAD) is the second least studied anxiety disorder
      and among the most difficult to treat. Dropout from psychotherapy is concerning
      as it is associated with poorer outcomes, leads to service inefficiencies and can
      disproportionately affect disadvantaged populations. No study to date has
      calculated a weighted mean dropout rate for GAD and explored associated
      correlates. METHODS: A systematic review was conducted using PsycINFO, Medline
      and Embase databases, identifying studies investigating individual
      psychotherapies for adults with GAD. Forty-five studies, involving 2224
      participants, were identified for meta-analysis. RESULTS: The weighted mean
      dropout rate was 16.99% (95% confidence interval 14.42%-19.91%). The Q-statistic
      indicated significant heterogeneity among studies. Moderator analysis and meta
      regressions indicated no statistically significant effect of client age, sex,
      symptom severity, comorbidity, treatment type, study type (randomized trial or
      not), study quality, number of sessions or therapist experience. CONCLUSIONS: In
      research investigating psychotherapy for GAD, approximately one in six clients
      can be expected to drop out of treatment. Dropout rate was not significantly
      moderated by the client, therapist or treatment variables investigated. Future
      research should specify the definition of dropout, reasons for dropout and
      associated correlates to assist the field's progression.

PMID- 29028611
TI  - Automatic imitation of pro- and antisocial gestures: Is implicit social behavior
      censored?
AB  - According to social reward theories, automatic imitation can be understood as a
      means to obtain positive social consequences. In line with this view, it has been
      shown that automatic imitation is modulated by contextual variables that
      constrain the positive outcomes of imitation. However, this work has largely
      neglected that many gestures have an inherent pro- or antisocial meaning. As a
      result of their meaning, antisocial gestures are considered taboo and should not
      be used in public. In three experiments, we show that automatic imitation of
      symbolic gestures is modulated by the social intent of these gestures. Experiment
      1 (N=37) revealed reduced automatic imitation of antisocial compared with
      prosocial gestures. Experiment 2 (N=118) and Experiment 3 (N=118) used a social
      priming procedure to show that this effect was stronger in a prosocial context
      than in an antisocial context. These findings were supported in a within-study
      meta-analysis using both frequentist and Bayesian statistics. Together, our
      results indicate that automatic imitation is regulated by internalized social
      norms that act as a stop signal when inappropriate actions are triggered.

PMID- 29028612
TI  - Where do spontaneous first impressions of faces come from?
AB  - Humans spontaneously attribute a wide range of traits to strangers based solely
      on their facial features. These first impressions are known to exert striking
      effects on our choices and behaviours. In this paper, we provide a theoretical
      account of the origins of these spontaneous trait inferences. We describe a novel
      framework ('Trait Inference Mapping') in which trait inferences are products of
      mappings between locations in 'face space' and 'trait space'. These mappings are
      acquired during ontogeny and allow excitation of face representations to
      propagate automatically to associated trait representations. This
      conceptualization provides a framework within which the relative contribution of
      ontogenetic experience and genetic inheritance can be considered. Contrary to
      many existing ideas about the origins of trait inferences, we propose only a
      limited role for innate mechanisms and natural selection. Instead, our model
      explains inter-observer consistency by appealing to cultural learning and
      physiological responses that facilitate or 'canalise' particular face-trait
      mappings. Our TIM framework has both theoretical and substantive implications,
      and can be extended to trait inferences from non-facial cues to provide a unified
      account of first impressions.

PMID- 29028613
TI  - Divergent biology of facultative heavy metal plants.
AB  - Among heavy metal plants (the metallophytes), facultative species can live both
      in soils contaminated by an excess of heavy metals and in non-affected sites. In
      contrast, obligate metallophytes are restricted to polluted areas. Metallophytes
      offer a fascinating biology, due to the fact that species have developed
      different strategies to cope with the adverse conditions of heavy metal soils.
      The literature distinguishes between hyperaccumulating, accumulating, tolerant
      and excluding metallophytes, but the borderline between these categories is
      blurred. Due to the fact that heavy metal soils are dry, nutrient limited and are
      not uniform but have a patchy distribution in many instances, drought-tolerant or
      low nutrient demanding species are often regarded as metallophytes in the
      literature. In only a few cases, the concentrations of heavy metals in soils are
      so toxic that only a few specifically adapted plants, the genuine metallophytes,
      can cope with these adverse soil conditions. Current molecular biological studies
      focus on the genetically amenable and hyperaccumulating Arabidopsis halleri and
      Noccaea (Thlaspi) caerulescens of the Brassicaceae. Armeria maritima ssp. halleri
      utilizes glands for the excretion of heavy metals and is, therefore, a heavy
      metal excluder. The two endemic zinc violets of Western Europe, Viola lutea ssp.
      calaminaria of the Aachen-Liege area and Viola lutea ssp. westfalica of the Pb-Cu
      ditch of Blankenrode, Eastern Westphalia, as well as Viola tricolor ecotypes of
      Eastern Europe, keep their cells free of excess heavy metals by arbuscular
      mycorrhizal fungi which bind heavy metals. The Caryophyllaceae, Silene vulgaris
      f. humilis and Minuartia verna, apparently discard leaves when overloaded with
      heavy metals. All Central European metallophytes have close relatives that grow
      in areas outside of heavy metal soils, mainly in the Alps, and have, therefore,
      been considered as relicts of the glacial epoch in the past. However, the current
      literature favours the idea that hyperaccumulation of heavy metals serves plants
      as deterrent against attack by feeding animals (termed elemental defense
      hypothesis). The capability to hyperaccumulate heavy metals in A. halleri and N.
      caerulescens is achieved by duplications and alterations of the cis-regulatory
      properties of genes coding for heavy metal transporting/excreting proteins.
      Several metallophytes have developed ecotypes with a varying content of such
      heavy metal transporters as an adaption to the specific toxicity of a heavy metal
      site.

PMID- 29028614
TI  - Simultaneous determination of five Alternaria toxins in cereals using QuEChERS
      based methodology.
AB  - Two analytical approaches, including ultra-high performance liquid chromatograph
      linked with photo-diode array/fluorescence detector, and ultra-high performance
      liquid chromatography-tandem mass spectrometry, have been proposed for
      simultaneous determination of five Alternaria toxins in cereals, which both based
      on QuEChERS strategy. After QuEChERS extraction and salting out, the collected
      supernatant was subjected to an extra dispersive liquid-liquid microextraction
      step prior to quantitative analysis. Response surface methodology based on
      central composite design was employed to optimize the micro-extraction
      conditions. During photo-diode array/fluorescence detector method validation,
      satisfactory analytical characteristics, in terms of selectivity, recovery (72.7%
      109.1%), precision (inter-day RSDs <9.6%), sensitivity (limits of quantification
      ranged from 2.1MUgkg-1 to 120.0MUgkg-1) and linearity (R2 all higher than
      0.9984), were achieved. Mass spectrometry method was employed as a certified
      method for accuracy. The two methodologies were successfully applied to 71
      samples including three different matrices and the quantitative results were
      compared. As the result of non-parametric test shown, the established two
      analytical approach exhibited comparable quantitative accuracy to each other.

PMID- 29028615
TI  - Determination of quinolones in wastewater by porous beta-cyclodextrin polymer
      based solid-phase extraction coupled with HPLC.
AB  - In this research, a novel insoluble sorbent based on cyclodextrin and rigid
      aromatic groups tetrafluoroacetonitrile was designed for dispersive insoluble
      solid-phase extraction (DSPE). Due to its high adsorption capacity, this obtained
      polymer was applied to separation and concentration of trace quinolones in
      wastewater before HPLC determination. Various parameters influencing the
      extraction performance were studied and optimized. A DSPE approach coupled with
      high performance liquid chromatography was developed for the determination of
      four quinolones in wastewater samples. The limit of quantitation of fleroxacin,
      ciprofloxacin, gatifloxacin, norfloxacin were 2.67, 3.17, 4.75, 5.50ngmL-1,
      respectively. The recoveries of four quinolones range from 96.43 to 103.3% with
      relative standard deviations less than 4.5%. These results demonstrated that the
      proposed approach based on CDP was efficient, low-cost for extraction of
      quinolones from wastewater.

PMID- 29028616
TI  - Simultaneous determination of a novel c-Met/AXL dual-target small-molecule
      inhibitor BPI-9016M and its metabolites in human plasma by liquid chromatography
      tandem mass spectrometry: Application in a pharmacokinetic study in Chinese
      advanced solid tumor patients.
AB  - BPI-9016M is a novel dual-target small-molecule inhibitor targeting c-Met and
      AXL, which was developed by Betta Pharmaceuticals Co., Ltd (Hangzhou, China). It
      has great potential in the treatment of advanced cancer. A high throughput
      quantitation method, based on liquid chromatography-tandem mass spectrometry, was
      developed and validated for the simultaneous determination of BPI-9016M and its
      main metabolite, M1 and M2-2, in human plasma with a sample preparation method of
      precipitation of protein. Liquid chromatographic separation was performed with a
      gradient elution of formic acid-10mM ammonium acetate aqueous solution (1:1000,
      v/v) and acetonitrile at a flow rate of 0.4mL/min within 2.2min. A Waters ACQUITY
      UPLC BEH C18 column (1.7MUm, 2.1*50mm) was chosen, of which the temperature was
      set to be 40 degrees C. Mass spectrometric detection, which were achieved in
      positive mode, were performed by multiple reaction monitoring with SCIEX API 5500
      Qtrap equipped with an ESI ion source. This method showed good linearity,
      accuracy and precision in the range of 0.4-200ng/mL for BPI-9016M and 0.8
      800ng/mL for M1 and M2-2, with high recovery and slight matrix effect for all
      analytes. And under the conditions same as stability assessments in method
      validation, the three analytes stayed stable during the entire destiny of a
      clinical sample from the collection of whole blood to the analysis of plasma by
      this method. The validated method was successfully applied to a first-in-human,
      dose-escalation phase I clinical trial in Chinese advanced solid tumor patients
      for the pharmacokinetic research of BPI-9016M tablet after oral administration.
      The concentration-time curves of BPI-9016M, M1, M2-2 were detailly captured with
      good veracity. And according to the results of hemolysis assessment, plasma
      concentrations of analytes in hemolyzed plasma samples could be reported normally
      without label.

PMID- 29028617
TI  - A plasma lipidomics strategy reveals perturbed lipid metabolic pathways and
      potential lipid biomarkers of human colorectal cancer.
AB  - To explore underlying molecular mechanisms and identify novel lipid biomarkers
      promising for colorectal cancer (CRC) diagnosis, a continuous-flow two
      dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (2D
      LC-QToF/MS) method was employed to comprehensively measure lipid species in human
      plasma of CRC patients and healthy controls. With a total of 427 annotated lipid
      species, we identified 64 lipid species with corrected p value less than 0.05 and
      fold change more than 1.5. These significantly altered lipid species were mainly
      involved in glycerolipids and glycerophospholipids metabolism and sphingolipids
      metabolism. After the diagnosis ability evaluation based on the receiver
      operating characteristic (ROC) curve, phosphatidylglycerol (34:0), sphingomyelin
      (42:2), ceramide (44:5), lysophosphatidylcholine (18:3), lysophosphatidylcholine
      (18:2), phosphatidylethanolamine (O-36:3), phosphatidylethanolamine (O-38:3) and
      sphingomyelin (38:8) were finally proposed as the potential biomarkers with the
      area under the curve (AUC) more than 0.900. These results suggest that this 2D LC
      QToF/MS-based lipidomics profiling has great potential as a noninvasive
      diagnostic method in detecting CRC and hopefully provide new clues to understand
      its underlying mechanism.

PMID- 29028618
TI  - One single standard substance for the simultaneous determination of 17
      triterpenes in Ganoderma lingzhi and its related species using high-performance
      liquid chromatography.
AB  - Due to the difficulty and high cost for the preparation of triterpenes, one
      single standard for the simultaneous determination of multi-components (SSDMC)
      with high performance liquid chromatography (HPLC) is an advanced solution for
      multi-component analysis. Experiments were carried out to investigate the
      feasibility of SSDMC for the analysis of Ganoderma triterpenes, with external
      standard method (ESM) compared, and the samples of Ganoderma were classified by
      the content of Ganoderma triterpenes. The analysis was performed by using a
      Fortis Speed Core-C18 column (150mm*4.6mm I.D., 2.6MUm) at gradient elution of
      0.01% glacial acetic acid-water (V/V) and acetonitrile with diode array detection
      (252nm), at a flow rate of 1mL/min. The results showed that all calibration
      curves had good linearity (r2>0.9999) within test ranges. The LOD and LOQ were
      lower than 2.52ng and 6.43ng, respectively. The RSD for intra-day and inter-day
      of the seventeen analytes were less than 3.12% at three levels, and the
      recoveries were 91.4-103.0%. The contents of other 16 triterpenes were determined
      with ganoderic acid A by SSDMC, which showed that there were few differences
      compared with the results obtained by ESM. Moreover, the classification of 25
      different species and strains of Ganoderma by using the content of triterpenes
      intuitively reflected the distinction among Ganoderma. In summary, the developed
      method could be readily utilized as a method of quality evaluation for Ganoderma
      triterpenes.

PMID- 29028619
TI  - Development of a high-performance liquid chromatography method for the
      determination of florfenicol in animal feedstuffs.
AB  - An effective thin layer chromatography (TLC) purification procedure coupled to
      high-performance liquid chromatography (HPLC) method was developed for the
      determination of florfenicol (FF) in pig, chicken and fish feedstuffs. The
      feedstuff samples were extracted with ethyl acetate, defatted with n-hexane
      saturated with acetonitrile, and further purified by TLC. The chromatographic
      separation was performed on a Waters Symmetry C18 column using an isocratic
      procedure with acetonitrile-water (35:65, v/v) at 0.6mL/min. The ultraviolet (UV)
      detector was set at a wavelength of 225nm. The FF concentrations in feedstuff
      samples were quantified using a standard curve. Good linear correlations
      (y=159075x-15054, r>0.9999) were achieved within the concentration range of 0.05
      200MUg/mL. The recoveries of FF spiked at levels of 1, 100 and 1000MUg/g ranged
      from 80.6% to 105.3% with the intra-day and inter-day relative standard deviation
      (RSD) less than 9.3%. The limit of detection (LOD) and limit of quantitation
      (LOQ) were 0.02 and 0.06mg/kg for pig feedstuffs, 0.02 and 0.07mg/kg for chicken
      feedstuffs, and 0.02 and 0.05mg/kg for fish feedstuffs, respectively. This
      reliable, simple and cost-effective method could be applied to the routine
      monitoring of FF in animal feedstuffs.

PMID- 29028620
TI  - Carbon emission analysis and evaluation of industrial departments in China: An
      improved environmental DEA cross model based on information entropy.
AB  - Environmental protection and carbon emission reduction play a crucial role in the
      sustainable development procedure. However, the environmental efficiency analysis
      and evaluation based on the traditional data envelopment analysis (DEA) cross
      model is subjective and inaccurate, because all elements in a column or a row of
      the cross evaluation matrix (CEM) in the traditional DEA cross model are given
      the same weight. Therefore, this paper proposes an improved environmental DEA
      cross model based on the information entropy to analyze and evaluate the carbon
      emission of industrial departments in China. The information entropy is applied
      to build the entropy distance based on the turbulence of the whole system, and
      calculate the weights in the CEM of the environmental DEA cross model in a
      dynamic way. The theoretical results show that the new weight constructed based
      on the information entropy is unique and optimal globally by using the Monte
      Carlo simulation. Finally, compared with the traditional environmental DEA and
      DEA cross model, the improved environmental DEA cross model has a better
      efficiency discrimination ability based on the data of industrial departments in
      China. Moreover, the proposed model can obtain the potential of carbon emission
      reduction of industrial departments to improve the energy efficiency.

PMID- 29028621
TI  - Combining valgus knee brace and lateral foot wedges reduces external forces and
      moments in osteoarthritis patients.
AB  - Osteoarthritis progression can be related to the external knee adduction and
      flexion moments during walking. Lateral foot wedges and knee braces have been
      used as treatment for osteoarthritis, but little is known about their influence
      on knee joint moments generated in the sagittal and frontal planes. Therefore,
      the aim of the present study was determine the effects of the isolated and
      combined use of valgus knee brace and lateral wedge foot orthotic on peak forces
      and moments during gait in knee osteoarthritis patients. Twenty four males (age:
      62.1+/-2.0years) with varus alignment, symptomatic medial compartment knee
      osteoarthritis participated in this study. Subjects walked over ground at
      preferred speed in four conditions: (1) no assistive device (control); (2) using
      lateral wedges, (3) using knee braces, and (4) using both lateral wedges and knee
      braces. Ground reaction forces (GRF) and moments, as well as lower limb
      kinematics were recorded. Peak GRF, vertical loading rate, free moment, external
      knee adduction and flexion moments were compared across conditions. The
      concurrent use of lateral wedge and knee brace reduced the first peak GRF in the
      vertical (6%, p=0.002), anterior-posterior (30%, p=0.028) and medial-lateral
      directions (44%, p=0.029). Moreover, the use of these devices reduced the peak
      external knee adduction moment (25%, p=0.019), but not the external flexion
      moment and free moment (p>0.05). The combined use of lateral wedges and knee
      braces can reduce medial-lateral knee joint loading, but despite reduced peak
      forces in the sagittal plane, these device do not reduce joint moments.

PMID- 29028623
TI  - Constraints specific influences of vision, touch and surface compliance in
      postural dynamics.
AB  - Studies that have manipulated vision and touch in posture usually emphasize the
      prescriptive closed-loop function of the information to reduce the amount of
      postural motion. In contrast, we examine here the hypothesis that the standard
      sensory manipulations to maintain quiet stance also change in specific ways the
      constraints on the task goal and the emergent movement organization. Twelve
      participants were instructed to maintain quiet postural stance under three
      sensory factors: surface compliance (foam/no foam), visual information
      (open/closed eyes) and tactile information (finger touch/no finger touch). The
      standard deviation of center of pressure (COP) motion decreased with the presence
      of vision, touch and rigid surface. The correlation dimension showed that the
      manipulation of touch and vision produced different attractor dynamics that also
      interacted with surface compliance. Vision decreased the correlation dimension in
      the foam surface while the touch manipulation increased dimension in the rigid
      surface. The sensory information manipulations changed the qualitative properties
      of the attractor dynamics as well as the quantitative properties of the amount of
      postural motion providing evidence for the specific nature of the postural
      organization across information conditions.

PMID- 29028622
TI  - Virtual reality balance training for elderly: Similar skiing games elicit
      different challenges in balance training.
AB  - BACKGROUND: Virtual Reality (VR) balance training may have advantages over
      regular exercise training in older adults. However, results so far are
      conflicting potentially due to the lack of challenge imposed by the movements in
      those games. Therefore, the aim of this study was to assess to which extent two
      similar skiing games challenge balance, as reflected in center of mass (COM)
      movements relative to their Functional Limits of Stability (FLOS). METHODS:
      Thirty young and elderly participants performed two skiing games, one on the Wii
      Balance board (Wiiski), which uses a force plate, and one with the Kinect sensor
      (Kinski), which performs motion tracking. During gameplay, kinematics were
      captured using seven opto-electronical cameras. FLOS were obtained for eight
      directions. The influence of games and trials on COM displacement in each of the
      eight directions, and maximal COM speed, were tested with Generalized Estimated
      Equations. RESULTS: In all directions with anterior and medio-lateral, but not
      with a posterior component, subjects showed significantly larger maximal %FLOS
      displacements during the Kinski game than during the Wiiski game. Furthermore,
      maximal COM displacement, and COM speed in Kinski remained similar or increased
      over trials, whereas for Wiiski it decreased. CONCLUSIONS: Our results show the
      importance of assessing the movement challenge in games used for balance
      training. Similar games impose different challenges, with the control sensors and
      their gain settings playing an important role. Furthermore, adaptations led to a
      decrease in challenge in Wiiski, which might limit the effectiveness of the game
      as a balance-training tool.

PMID- 29028624
TI  - Foot pressure pattern, hindfoot deformities, and their associations with foot
      pain in individuals with advanced medial knee osteoarthritis.
AB  - This survey clarified foot pressure patterns and hindfoot deformities in
      individuals with advanced knee osteoarthritis (OA) and analyzed their
      associations with foot pain. Sixty-four individuals with unilateral knee OA who
      underwent total knee arthroplasty (TKA) were divided into the following groups:
      no foot pain (n=26; men:women, 4:22; mean age, 73.7 years), foot pain resolved
      after TKA (12; 2:10; 75.8), and foot pain remaining after TKA (26; 4:22; 74.7).
      Elderly individuals without pain or deformity in either knee (54; 10:44; 74.3)
      were controls. Navicular height ratio of the medial longitudinal arch, leg-heel
      angle, and partial foot pressure as the percentage of body weight (%PFP) were
      calculated.%PFPs of the medial and lateral heel regions before TKA were
      significantly lower for the no foot pain group than for controls. One year after
      TKA, %PFP improved significantly. In the foot pain resolved group, before TKA,
      the leg-heel angle was significantly higher, and%PFPs of the medial and lateral
      heel regions and navicular height ratio before TKA were significantly lower than
      those of controls. One year after TKA, all parameters improved significantly. In
      the foot pain remaining group, similar abnormalities were observed before TKA;
      however, significant improvement was only observed for%PFP of the medial heel
      region 1year after TKA. More than half of the patients with advanced knee OA had
      foot pain. This improved in approximately one-third, 1year after TKA. Hindfoot
      deformities are probably associated with foot pain in individuals with advanced
      knee OA.

PMID- 29028625
TI  - Difference in kick motion of adolescent soccer players in presence and absence of
      low back pain.
AB  - Many adolescent soccer players experience low back pain (LBP). However, there are
      no reports studying the kick motion of adolescent soccer players experiencing
      LBP. This study aimed to clarify the kick motion of adolescent soccer players in
      the presence and absence of LBP. We recruited 42 adolescent soccer players and
      divided them into two groups according to the presence of LBP (LBP group, n=22)
      and absence of LBP (NBP group, n=20). We measured real-time kick motion using a
      three-dimensional motion analysis system. We placed 65 spherical markers on each
      anatomical landmark and calculated the angle of the lumbar spine, center of mass
      (COM) of the whole body, and displacement of the support foot. We used an
      unpaired t-test to compare the data between the groups. Compared with the NBP
      group, the LBP group showed a lateral shift in COM, which increased the duration
      of kick motion. The presence of LBP affected the posterior positioning of the
      support foot and restricted the player's lumbar spine from bending laterally. A
      lateral shift in COM and larger rotation of the lumbar spine could stress the
      lumbar spine during kick motion. Therefore, coaches and athletic trainers should
      pay attention to soccer players' lumbar spine rotation and the COM shift during
      kick motion. This would be important for preventing LBP in adolescent soccer
      players.

PMID- 29028626
TI  - Accuracy of three methods in gait event detection during overground running.
AB  - Inertial measurement units (IMUs) have been extensively used to detect gait
      events. Various methods have been proposed for detecting initial contact (IC) and
      toe-off (TO) using IMUs affixed at various anatomical locations. However, the
      accuracy of such methods has yet to be compared. This study evaluated the
      accuracy of three common methods used for detecting gait events during jogging
      and running: (1) S-method, in which IC is identified as the instant of peak foot
      resultant acceleration and TO is identified when the acceleration exceeds a
      threshold of 2g in the region of interest; (2) M-method, in which IC and TO are
      defined as the minimum before the positive peak shank vertical acceleration and
      the minimum in the region of interest, respectively; and (3) L-method, in which
      IC is indicated by the instant of peak pelvis anteroposterior acceleration and TO
      is identified by the maximum in the region of interest. The performance of the
      IMU-based methods in detecting IC and TO and estimating stance time (ST) were
      tested on 11 participants at jogging and running speeds against a reference
      provided by a force-platform method. The S-method was the most accurate for IC
      detection (overall mean absolute difference (MAD): 4.7+/-4.1ms). The M-method was
      the most accurate for TO detection (overall MAD: 7.0+/-3.5ms). A combination of M
      and S-methods, called the MS-method, was the most accurate for ST estimation
      (overall MAD: 9.0+/-3.9ms). Thus, the MS-method is recommended for ST estimation;
      however, this method requires four IMUs for bilateral estimation.

PMID- 29028627
TI  - Local dynamic stability during treadmill walking can detect children with
      developmental coordination disorder.
AB  - OBJECTIVE: Developmental coordination disorder (DCD) is an innate impairment of
      motor coordination that affects basic locomotion and balance. This study
      investigated local dynamic stability of trunk accelerations during treadmill
      walking as an objective evaluation of gait stability and the sensitivity and
      specificity of this measure to discriminate children with DCD from typically
      developing children. METHOD: Eight children with DCD and ten age- and gender
      matched typically developing children (TD) walked four minutes on a treadmill.
      Trunk accelerations in vertical, medio-lateral and anterior-posterior directions
      were recorded with a sternum mounted accelerometer at 256Hz. Short term local
      dynamic stability (lambdas), root mean square (RMS) and relative root mean square
      (RMSR) were calculated from measures of orthogonal trunk accelerations. Receiver
      operating characteristic curve (ROC) analysis was performed to discriminate
      between groups based on short term local dynamic stability. RESULTS: lambdas was
      significantly greater in children with DCD in the main movement direction (AP)
      (DCD: 1.69+/-0.17 lambdas; TD:1.41+/-0.17 lambdas; p=0.005), indicating reduced
      local dynamic stability. RMS and RMSR accelerations showed no difference between
      children with DCD and TD children in any direction. The ROC analysis of lambdas
      in separate directions and in two dimensions showed an excellent accuracy of
      discriminating between children with DCD and TD children. Anterior-posterior
      direction in combination with medio-lateral or vertical showed best performance
      with an area under the curve (AUC) of 0.91. CONCLUSION: We have shown that
      children with developmental coordination disorder have general reduced local
      dynamic stability and that the short term Lyapunov exponent has good power of
      discrimination between DCD and TD.

PMID- 29028628
TI  - Role of PDGF-BB in proliferation, differentiation and maintaining stem cell
      properties of PDL cells in vitro.
AB  - OBJECTIVE: Platelet-derived growth factor-BB (PDGF-BB) is one of the most
      abundant growth factors in platelet derived products and has been shown to
      stimulate regeneration after tissue injury. There is a population of mesenchymal
      stem cells (MSC) in human periodontal ligament (PDL) which can contribute to
      tissue regeneration under appropriate conditions. DESIGN: PDL cells were isolated
      and characterized using stem cell and differentiation markers via
      immunofluorescence and flow cytometry and then cultured in vitro and treated with
      different concentrations of PDGF-BB. The effect of PDGF-BB on cell proliferation,
      stem cell and differentiation markers expression, soluble collagen production,
      lysyl oxidase (LOX) activity, alkaline phosphatase (ALP) activity and calcium
      nodules formation was assessed. RESULTS: PDGF-BB stimulated the proliferation of
      cells with the maximum effect at 50ng/mL. The growth factor increased the
      expression of stem cell markers and SPARC; Col1a2 expression was decreased,
      whereas the expression of Col3a1 remain unchanged. Soluble collagen production,
      ALP activity and calcium nodules formation were also significantly decreased by
      PDGF-BB; LOX activity was significantly increased. CONCLUSIONS: PDGF-BB is a
      powerful promoter of cell proliferation and increases the expression of stem cell
      markers; inhibites collagen production and mineraliration but accelerates the
      maturation of collagen chains through increased LOX activity and SPARC
      expression.

PMID- 29028629
TI  - A dual energy micro-CT methodology for visualization and quantification of
      biofilm formation and dentin demineralization.
AB  - OBJECTIVE: The aim of this study was to induce artificial caries in human sound
      dentin by means of a microcosm model using human saliva as source of bacteria and
      to apply a novel dual-energy micro-CT technique to quantify biofilm formation and
      evaluate its demineralization potential. DESIGN: Eight sound third molars had the
      occlusal enamel removed by cutting with a diamond disk and five cylindrical
      cavities (+/-2mm diameter; +/-1.5mm depth) were prepared over the dentin surface
      in each specimen (n=40 cavities). After sterilization, each specimen received the
      bacterial salivary inoculum obtained from individuals without any systemic
      diseases presenting dentin caries lesions and were incubated in BHI added of with
      5% sucrose for 96h to allow biofilm formation. After that, two consecutive micro
      CT scans were acquired from each specimen (40kv and 70kv). Reconstruction of the
      images was performed using standardized parameters. After alignment,
      registration, filtering and image calculations, a final stack of images
      containing the biofilm volume was obtained from each prepared cavity. Dentin
      demineralization degree was quantified by comparison with sound dentin areas. All
      data were analyzed using Shapiro-Wilk test and Spearman correlation using
      alpha=5%. RESULTS: Dual-energy micro-CT technique disclosed biofilm formation in
      all cavities. Biofilm volume inside each cavity varied from 0.30 to 1.57mm3. A
      positive correlation between cavity volume and volume of formed biofilm was
      obtained (0.77, p<0.01). The mineral decrease obtained in dentin was high (+/
      90%) for all cavities and all demineralized areas showed mineral density values
      lower than a defined threshold for dentin caries (1.2g/cm3). CONCLUSION: Dual
      energy micro-CT technique was successful in the quantification of a microcosm
      human bacterial biofilm formation and to quantify its demineralization potential
      in vitro.

PMID- 29028631
TI  - Sexual behavior and pregnancy among adolescents in foster family homes.
AB  - Objective To examine the prevalence of and factors associated with sexual
      behavior and pregnancy involvement among adolescents in foster family homes.
      Methods A cross-sectional study was conducted among a random sample of children
      living in foster family homes. Logistic regression with Firth's correction was
      used to determine factors associated with sexual risk behavior and pregnancy
      involvement (i.e. having been pregnant or gotten someone pregnant). Results About
      half of adolescents (aged 13-18 years) in foster family homes ever had sex, of
      whom, one third had first sex before the age of 14 and one sixth had two or more
      sexual partners in the past 3 months. Of adolescents in the study, 9% had ever
      been pregnant or gotten someone pregnant. Although adolescents in foster family
      homes had higher rates of sex initiation and pregnancy involvement than those in
      the general population, the two groups had comparable rates of current sexual
      risk behavior. Being placed in kin/fictive kin foster homes [odds ratio (OR):
      3.04; 95% confidence interval (CI): 1.18-7.80] and number of placement settings
      (OR: 1.20; 95% CI: 1.02-1.42) were associated with multiple sexual partners,
      while a history of running away from a foster home (OR: 7.64; 95% CI: 1.87-31.18)
      was associated with pregnancy involvement. Conclusions Efforts targeting
      placement stability including prevention of running away may reduce sexual risk
      behavior and pregnancy involvement among adolescents in foster family homes.

PMID- 29028630
TI  - EZH2 regulates dental pulp inflammation by direct effect on inflammatory factors.
AB  - OBJECTIVE: Pulpitis is a multi-factorial disease that could be caused by complex
      interactions between genetics, epigenetics and environmental factors. We aimed to
      evaluate the role of Enhancer of Zeste Homolog 2 (EZH2) in the inflammatory
      response of human dental pulp cells (HDPCs) and dental pulp tissues. METHODS: The
      expressions of inflammatory cytokines in HDPCs treated by EZH2 complex or EZH2
      siRNA with or without rhTNF-alpha were examined by quantitative real-time
      polymerase chain reaction (q-PCR). The levels of secreted inflammatory cytokines
      including IL-6, IL-8, IL-15, CCL2 and CXCL12 in culture supernatants were
      measured by Luminex assay. In rat pulpitis model, the effects of EZH2 on dental
      pulp tissues were verified by histology. We invested the mechanisms of the effect
      of EZH2 on the inflammatory factors by ChIP assay. RESULTS: EZH2 down-regulation
      inhibited the expression of inflammatory factors, including IL-6, IL-8, IL-15,
      CCL2 and CXCL12 in HDPCs. EZH2 complex promoted the expression and secretion of
      these inflammatory factors in HDPCs, while EZH2 silencing could attenuate the
      promotion of inflammatory factors that were induced by rhTNF-alpha. In pulpitis
      models of rats, EZH2 down-regulation inhibited the inflammatory process of dental
      pulp while EZH2 complex showed no significant facilitation of pulpal
      inflammation. In addition, EZH2 could bind on the promoters of IL-6, IL-8 and
      CCL2, but not IL-15 and CXCL12, to affect the transcription of these
      proinflammatory cytokines. CONCLUSIONS: In HDPCs, EZH2 could induce inflammation,
      while EZH2 down-regulation could attenuate the inflammatory responses. EZH2 plays
      an important role in this inflammatory process of dental pulp.

PMID- 29028632
TI  - Procalcitonin as a diagnostic and prognostic marker in diabetic foot infection. A
      current literature review.
AB  - Diabetic foot ulcers (DFUs) are a very common cause of mortality and morbidity.
      The distinction between infected and non-infected DFU remains a very challenging
      task for clinicians in everyday practice. Even when infection is documented, the
      spectrum of diabetic foot infection is wide, ranging from cellulitis and soft
      tissue infection to osteomyelitis. Procalcitonin (PCT), a well-established sepsis
      biomarker, has been used in the diagnosis of several infections including
      osteomyelitis in patients with diabetes mellitus. This review gathers and
      presents all the relevant data, up until now, regarding the use of PCT as an
      assessment tool in diabetic patients with foot infection. Current evidence
      suggests that PCT levels could aid clinicians in distinguishing infected from non
      infected DFUs as well as in the distinction between soft tissue infection and
      bone involvement, but further and larger studies are warranted to confirm these
      findings.

PMID- 29028633
TI  - Acute kidney injury in congenital heart disease.
AB  - PURPOSE OF REVIEW: Acute kidney injury (AKI) is associated with significant
      morbidity and mortality in patients with congenital heart disease undergoing
      cardiac surgery or in pediatric patients with congestive heart failure. RECENT
      FINDINGS: This review describes the definition and various manifestations of AKI,
      the impact of biomarkers on the diagnosis of AKI, the importance of fluid
      overload as a consequence of AKI and its long-term impact. SUMMARY: There are
      novel biomarkers for AKI detection that should facilitate early recognition and
      intervention to prevent or attenuate the effects of AKI and fluid overload.
      Previous conventional wisdom that survivors of AKI fully recover renal function
      without subsequent consequences is flawed.

PMID- 29028634
TI  - Establishing a successful transition care plan for the adolescent with congenital
      heart disease.
AB  - PURPOSE OF REVIEW: In this review we explore the aspects needed to develop a
      successful transition program for adolescents with congenital heart disease and
      the barriers that exist to the development of such a program. RECENT FINDINGS: We
      review the literature including more recent publications which support the
      development of a transition program in order to facilitate transfer from the
      pediatric to the adult healthcare system. SUMMARY: With the development of a
      successful transition program patients will hopefully receive high-quality,
      continuous life-long care in the appropriate setting.

PMID- 29028635
TI  - Are We on the Same Page? Shared Mental Models to Support Clinical Teamwork Among
      Health Professions Learners: A Scoping Review.
AB  - PURPOSE: To conduct a scoping review to explore the construct of shared mental
      models (SMMs) in the context of clinical teamwork among health professions
      learners. METHOD: The authors searched the PubMed, ERIC, CINAHL, Scopus, Web of
      Science, PsychINFO, and EMBASE databases for English-language articles published
      between 2000 and 2016. Eligible articles mentioned SMMs in relation to clinical
      teamwork and included health professions learners. Two reviewers screened studies
      for eligibility and extracted data to determine the depth and breadth of the
      literature on SMMs. The authors examined definitions of the SMM construct in the
      context of clinical teams, educational interventions using SMMs, and the
      measurement of SMMs. RESULTS: Of the 1,273 articles retrieved, 23 met the
      inclusion criteria. SMMs were defined in less than two-fifths of the articles
      (9/23). All articles applied the construct to improvements in hospital-based
      patient safety, often in high-intensity settings (14/23). Most articles included
      graduate-level physicians (21/23) within clinical teams (18/23). Interventions
      designed to foster SMMs (6/23) included teamwork curricula/training and teamwork
      supportive tools. Measurements of SMMs (7/23) included a qualitative task
      analysis, quantitative analyses of speech, a concept mapping, and Likert-type
      surveys. CONCLUSIONS: In health professions education, the SMM construct lacks
      clear definition. Few studies described educational interventions aimed at SMM
      development, and few attempted to measure the construct. The authors propose an
      operational definition of SMMs in health care and illustrate how interventions
      intended to foster SMMs, such as team trainings or planning exercises and
      communication tools, could be developed, implemented, and assessed.

PMID- 29028636
TI  - Effects and Unforeseen Consequences of Accessing References on a Maintenance of
      Certification Examination: Findings From a National Study.
AB  - PURPOSE: Increasing criticism of maintenance of certification (MOC) examinations
      has prompted certifying boards to explore alternative assessment formats. The
      purpose of this study was to examine the effect of allowing test takers to access
      reference material while completing their MOC Part III standardized examination.
      METHOD: Item response data were obtained from 546 physicians who completed a
      medical subspecialty MOC examination between 2013 and 2016. To investigate
      whether accessing references was related to better performance, an analysis of
      covariance was conducted on the MOC examination scores with references (access or
      no access) as the between-groups factor and scores from the physicians' initial
      certification examination as a covariate. Descriptive analyses were conducted to
      investigate how the new feature of accessing references influenced time
      management within the test day. RESULTS: Physicians scored significantly higher
      when references were allowed (mean = 534.44, standard error = 6.83) compared with
      when they were not (mean = 472.75, standard error = 4.87), F(1, 543) = 60.18, P <
      .001, omega = 0.09. However, accessing references affected pacing behavior;
      physicians were 13.47 times more likely to finish with less than a minute of test
      time remaining per section when reference material was accessible. CONCLUSIONS:
      Permitting references caused an increase in performance, but also a decrease in
      the perception that the test has sufficient time limits. Implications for
      allowing references are discussed, including physician time management, impact on
      the construct assessed by the test, and the importance of providing validity
      evidence for all test design decisions.

PMID- 29028637
TI  - Hemorrhagic Shock After Epicardial Pacing Wire Removal: A Case Report.
AB  - Epicardial pacing wires are routinely used to avoid hemodynamic instability due
      to perioperative arrhythmias after cardiac surgery. In rare cases, pacing wires
      themselves can be associated with potentially life-threatening complications.
      Herein, we present a novel case of hemorrhagic shock and hemoperitoneum after
      temporary epicardial pacing wire removal.

PMID- 29028639
TI  - Implications of Mitochondrial Dysfunction for the Anesthetic and Perioperative
      Management: A Case Report of Spinal Fusion, Genetic Confusion, and a Patient's
      Perspective.
AB  - We describe a patient's personal struggle with a symptom complex consisting of
      profound muscle weakness requiring pyridostigmine, and metabolic abnormalities
      suggestive of mitochondrial disease. This included a profound sensitivity to
      opioids, which in the past caused severe respiratory depression during a prior
      hospital admission. Interestingly, the patient herself is a professor of ethics
      in genomic sciences, and she and her medical team thus far have not been able to
      formally diagnose her with mitochondrial disease. The patient now presented for a
      multilevel lumbar spine fusion and her hospital course and perspective on her
      medical odyssey are described here.

PMID- 29028638
TI  - Malignant Hyperthermia Versus Thyroid Storm in a Patient With Symptomatic Graves
      Disease: A Case Report.
AB  - Malignant hyperthermia and thyroid storm are intraoperative emergencies with
      overlapping symptoms but different treatment protocols. We faced this diagnostic
      dilemma in a 25-year-old patient with symptomatic hyperthyroidism, elevated free
      T3 and free T4, and low thyroid-stimulating hormone from Graves disease despite
      treatment with propranolol 80 mg daily and methimazole 40 mg every 8 hours.
      During thyroidectomy, he developed hyperthermia and hypercarbia without
      tachycardia. When the rate of rise of PaCO2 and temperature accelerated, we
      treated the patient for malignant hyperthermia, a diagnosis subsequently
      confirmed by genetic testing.

PMID- 29028640
TI  - Coronary Sinus Catheter-Induced Heart Block During Aortic Valve Replacement: A
      Case Report.
AB  - Conduction abnormalities after cardiac surgery are common as is spontaneous
      resolution of these abnormalities. However, 1%-3% of patients will require
      placement of a permanent pacemaker. Patients with preexisting conduction
      abnormalities, undergoing reoperation, preexisting pulmonary hypertension and
      undergoing mitral or aortic valve operations are at a higher risk for requiring a
      permanent pacemaker. We present the first case described in the literature of a
      patient with a preexisting left bundle branch block, and heart failure with a
      reduced left ventricular ejection fraction of 25% who developed complete heart
      block after placement of a coronary sinus catheter.

PMID- 29028641
TI  - Postoperative care after tonsillectomy: what's the evidence?
AB  - PURPOSE OF REVIEW: The purpose of this review is to evaluate the current
      literature regarding postoperative management after tonsillectomy in children.
      RECENT FINDINGS: Controversy remains regarding the ideal medication regimen to
      manage pain after tonsillectomy. Acetaminophen and ibuprofen are routinely used,
      although concerns of more severe postoperative hemorrhage with ibuprofen remain.
      Narcotics are prescribed commonly, but with extreme caution in children with
      severe obstructive sleep apnea. Although not always utilized by the authors,
      additional adjunctive medications such as perioperative dexamethasone, ketamine,
      and local infiltration of lidocaine into tonsillar pillars may decrease
      postoperative pain. Systematic reviews have shown that dexamethasone does not
      increase risk of posttonsillectomy bleeding. SUMMARY: Adenotonsillectomy is one
      of the most common procedures performed on children and may have significant
      morbidity from postoperative pain and bleeding. Managing pain remains challenging
      and the optimal treatment regimen has not been definitively identified. Many
      medications and alternative therapies have been studied and suggest possible
      benefit.

PMID- 29028642
TI  - "Lost to Follow-up" Among Adult Cancer Survivors.
AB  - BACKGROUND: Follow-up cancer care is important for patients who have received IV
      chemotherapy but some patients discontinue their care and are lost to follow-up
      (LFU) at the cancer center where they were treated. The purpose of this study was
      to determine what proportion of cancer survivors are LFU at 5 years after
      treatment, the timing of LFU, and the characteristics of those who do not
      continue survivorship care. METHODS: Adult patients with cancer who were treated
      with chemotherapy at a large community teaching hospital in 2006 and 2007 were
      identified and linked with State tumor registry data. Hospital medical records
      were reviewed to obtain information on demographics, diagnosis, treatment, and
      date of last follow-up visit. Characteristics of patients with >=5 years of
      follow-up care were compared with those who were LFU. RESULTS: In total, 487
      patients received chemotherapy and 304 died (62%) during the 5-year follow-up
      period. Among the 183 cancer patients who were known to be alive at 5 years, 92
      (50%) were LFU and 50% (46/92) of this LFU group were LFU within 1 year of
      diagnosis. At 5 years, follow-up care was continuing for 55% of women, compared
      with 39% of men. The highest proportion of follow-up was observed among lung
      cancer patients (84%), followed by patients with breast cancers (63%) and
      gastrointestinal cancers (40%). Patients with hematological cancers had the
      lowest follow-up proportion at 5 years (29%) (P<0.05). Follow-up was not
      significantly associated with age (P=0.48), insurance status(P=0.29), and
      race(P=0.06). CONCLUSIONS: It is estimated that 65% of the cancer survivors in
      the United States are >=5 years beyond their diagnosis but there is little data
      on oncology follow-up rates. In our retrospective study of 183 patients who were
      treated with chemotherapy only 49.7% continue to follow-up at their treatment
      center. LFU has important implications in planning long-term care strategies for
      cancer survivors and in survivorship research.

PMID- 29028643
TI  - Pharmacotherapy of borderline personality disorder: replacing confusion with
      prudent pragmatism.
AB  - PURPOSE OF REVIEW: The article aims to examine trends in the pharmacological
      treatment of borderline personality disorder (BPD) and shed more light on the
      attendant controversies. RECENT FINDINGS: Although specialized, BPD-centred
      psychotherapy is considered first-line treatment for BPD and no psychotropic drug
      has been licensed for BPD, medications are frequently prescribed in the
      management of this condition. Various classes of psychopharmacological agents are
      used for BPD and there is a prominent polypharmacy. Use of antidepressants for
      BPD has been decreasing somewhat and use of mood stabilizers and second
      generation antipsychotics has been increasing. Although there is a general
      agreement that little evidence of efficacy of medications exists for BPD,
      clinicians are either advised to almost completely avoid pharmacotherapy for BPD
      or use a 'targeted' approach, administering specific medications for the specific
      symptoms of BPD. This has created some confusion in clinical practice and
      contributed to a variety of prescribing practices for BPD. SUMMARY: Well designed
      studies of the efficacy of pharmacological agents in BPD are needed. Clinicians
      should use medications for BPD with caution, usually short term and mainly for
      symptom relief. They should frequently review a need for ongoing pharmacotherapy
      and make every effort to avoid polypharmacy.

PMID- 29028644
TI  - The ageing-brain cognitive diseases: advances and promises.

PMID- 29028645
TI  - An update on the status of molecular testing for the indeterminate thyroid nodule
      and risk stratification of differentiated thyroid cancer.
AB  - PURPOSE OF REVIEW: Correct identification of malignancy in cytologically
      indeterminate thyroid nodules is a diagnostic challenge, leading to potentially
      unnecessary surgery in patients for whom final histology is benign. Similarly,
      many patients with differentiated thyroid cancer (DTC) undergo aggressive
      surgical management of tumors, which may ultimately have low-risk histologic
      features. Use of molecular testing strategies can aid in both the diagnosis of
      indeterminate thyroid nodules and preoperative risk stratification of DTC. RECENT
      FINDINGS: Validation studies of both the Afirma Gene Expression Classifier and
      Thyroseq Next-Generation Sequencing panel are ongoing. Both tests can be used to
      help rule out malignancy in indeterminate thyroid nodules. Recent additions to
      available molecular testing for indeterminate thyroid nodules include the Rosetta
      microRNA classifier and the augmentation of the ThyGenX gene panel with a
      microRNA reflex test (ThyraMIR). Mutational analysis of DTC shows that mutation
      in TERT alone, and in combination with other mutations, portends advanced
      disease. SUMMARY: Currently available molecular testing modalities are useful for
      ruling out malignancy in indeterminate thyroid nodules; however, longer-term
      follow-up studies are needed to confirm that test-negative nodules are truly
      benign. Analysis of specific gene mutations helps identify aggressive disease to
      guide prognostication and management, but further study is needed.

PMID- 29028646
TI  - Advances in understanding the molecular underpinnings of adrenocortical tumors.
AB  - PURPOSE OF REVIEW: Adrenocortical tumors are divided into benign adenomas and
      malignant carcinomas. The former is relatively common and carries a favorable
      prognosis, whereas the latter is rare and frequently presents at an advanced
      stage, with poor outcomes. Advances in next-generation sequencing, genome
      analysis, and bioinformatics have allowed for high-throughput molecular
      characterization of adrenal tumorigenesis. RECENT FINDINGS: Although recent
      genomic, epigenomic, and transcriptomic studies in large tumor cohorts have
      confirmed the central roles of aberrant Wnt/beta-catenin signaling, constitutive
      protein kinase A pathway activation, cell cycle dysregulation, and ion
      channelopathies in adrenal tumorigenesis, these studies also revealed novel
      signature events underlying malignant differentiation of adrenocortical
      carcinomas. SUMMARY: Recent advances in understanding of the molecular mechanisms
      underlying adrenocortical tumorigenesis provide new molecular diagnostic and
      prognostic tools and opportunities for novel therapeutic approaches. These
      findings are particularly important in adrenocortical carcinoma, for which
      current treatment options are limited.

PMID- 29028647
TI  - Change in Engagement in Cognitive Activity and Risk for Mild Cognitive Impairment
      in a Cohort of Older Adults: The Monongahela-Youghiogheny Healthy Aging Team
      (MYHAT) Study.
AB  - Engagement in cognitively stimulating activities is gaining prominence as a
      potential strategy to maintain cognitive functioning in old age. In a population
      based cohort of individuals aged 65+ years, we examined patterns of change in
      frequency of engagement in total cognitive activity (TCA), higher cognitive
      activity (HCA), and frequent cognitive activity (FCA) based on the Florida
      Cognitive Activities Scale over an average of 3.62 years, and whether these
      patterns were associated with incident mild cognitive impairment (MCI) during
      this same period. Among 867 cognitively normal participants, 129 (15%) progressed
      to MCI. Latent class trajectory modeling identified high and stable, slowly, and
      quickly declining patterns for TCA; high and stable, slowly declining, and
      slowing increasing patterns for FCA; and high and stable, and slowly declining
      patterns for HCA. Separate, adjusted Cox proportional hazard models, revealed
      that compared with the high, stable pattern, both slow decline [hazard ratio
      (HR), 2.5; 95% confidence interval (CI), 1.5-4.0] and quick decline (HR, 11.0;
      95% CI, 6.3-19.2) in TCA, and slow decline in the FCA (HR, 8.7; 95% CI, 5.3-14.3)
      and HCA (HR, 3.4; 95% CI, 2.0-5.6) subscales increased risk for incident MCI.
      Maintaining engagement in cognitive activities may be protective against
      progression to MCI, alternatively, declining engagement may be a marker for
      impending cognitive impairment.

PMID- 29028648
TI  - Gintonin Administration is Safe and Potentially Beneficial in Cognitively
      Impaired Elderly.

PMID- 29028649
TI  - [18F]-THK5351 PET Imaging in Patients With Semantic Variant Primary Progressive
      Aphasia.
AB  - BACKGROUND: Semantic variant primary progressive aphasia (svPPA) has been
      associated with a variety of proteinopathies, mainly transactive response DNA
      binding protein, but also with tau and beta-amyloid. Recently selective tau
      tracers for positron emission tomography (PET) have been developed to determine
      the presence of cerebral tau deposits in vivo. Here, we investigated the
      topographical distribution of THK5351 in svPPA patients. MATERIALS AND METHODS:
      Five svPPA patients, 14 Alzheimer's disease patients, and 15 age-matched normal
      controls underwent [F]-THK5351 PET scans, magnetic resonance imaging, and
      detailed neuropsychological tests. [F]-fluorodeoxyglucose PET was obtained in 3
      svPPA patients, whereas the remaining 2 underwent amyloid PET using [F]
      flutemetamol. Tau distribution among the 3 groups was compared using regions of
      interest-based and voxel-based statistical analyses. RESULTS: In svPPA patients,
      [F]-THK5351 retention was elevated in the anteroinferior and lateral temporal
      cortices compared with the normal controls group (left>right), and in the left
      inferior and temporal polar region compared with Alzheimer's disease patients.
      [F]-THK5351 retention inversely correlated with glucose metabolism, whereas
      regional THK retention correlated with clinical severity. [F]-flutemetamol scans
      were negative for beta-amyloid. CONCLUSIONS: These findings show that [F]-THK5351
      retention may be detected in cortical regions correlating with svPPA pathology.

PMID- 29028650
TI  - Fast digestive proteins and sarcopenia of aging.
AB  - PURPOSE OF REVIEW: The speed of dietary protein digestion influences postprandial
      amino acid availability which is crucial for improving altered anabolic response
      of skeletal muscle one feature of sarcopenia during aging. RECENT FINDINGS: By
      analogy with carbohydrate and in reference to their absorption rate, dietary
      proteins can be classified as 'fast' or 'slow' proteins depending on matrix food
      structure and technological processes, which can influence amino acids
      availability and their subsequent metabolic actions. 'Fast' digestive proteins
      have been shown to stimulate muscle protein synthesis and to improve muscle
      function in several recent studies involving older patients. These new aspects
      may be applied for improving health through preservation or restoration of muscle
      protein mass and function in clinical situations (obesity, rheumatoid arthritis
      and cancer cachexia). SUMMARY: Using fast digestive proteins is of major interest
      to overcome 'anabolic resistance' of aging for limiting sarcopenia. Fast
      proteins' action on muscle anabolism may be stimulated by other nutrients like
      vitamin D or omega 3 fatty acids or by combination with exercise. The beneficial
      impact of the 'fast' protein concept beyond the amount of dietary protein on
      muscle preservation is a promising therapeutic perspective to improve mobility
      and quality of life of older patients affected with chronic disease.

PMID- 29028651
TI  - Endoscopic Conduit Harvest in Coronary Artery Bypass Grafting Surgery: An ISMICS
      Systematic Review and Consensus Conference Statements.
AB  - OBJECTIVE: The purpose of this consensus conference was to develop and update
      evidence-informed consensus statements and recommendations on harvesting
      saphenous vein and radial artery via an open as compared with endoscopic
      technique by systematically reviewing and performing a meta-analysis of
      randomized and nonrandomized clinical trials. METHODS: All randomized controlled
      trials and nonrandomized controlled trials included in the first the
      International Society for Minimally Invasive Cardiothoracic Surgery Consensus
      Conference and Statements, in 2005 up to November 30, 2015, were included in a
      systematic review and meta-analysis. Based on the resultant, 76 studies (23
      randomized controlled trials and 53 nonrandomized controlled trials) on 281,459
      patients analyzed, consensus statements, and recommendations were generated
      comparing the risks and benefits of endoscopic versus open conduit harvesting for
      patients undergoing coronary artery bypass grafting. RESULTS: Compared with open
      vein harvest, it is reasonable to perform endoscopic vein harvest of saphenous
      vein to reduce wound-related complications, postoperative length of stay, and
      outpatient wound management resources and to increase patient satisfaction (class
      I, level A). Based on the quality of the conduit and major adverse cardiac events
      as well as 6-month angiographic patency, endoscopic vein harvest was noninferior
      to open harvest. It is reasonable to perform endoscopic radial artery harvest to
      reduce wound-related complication and to increase patient satisfaction (class I,
      level B-R and B-NR, respectively) with reduction in major adverse cardiac events
      and noninferior patency rate at 1 and 3 to 5 years (class III, level B-R).
      CONCLUSIONS: Based on the consensus statements, the consensus panel recommends
      (class I, level B) that endoscopic saphenous vein and radial artery harvesting
      should be the standard of care for patients who require these conduits for
      coronary revascularization.

PMID- 29028653
TI  - Adams-Oliver Syndrome With Moyamoya Disease for Cerebral Revascularisation
      Surgery.

PMID- 29028652
TI  - Novel Dry-Lab Training Method for Totally Endoscopic Coronary Anastomosis: A
      Pilot Study.
AB  - OBJECTIVE: We describe our original dry-lab training system for nonrobotic and
      beating heart endoscopic coronary artery anastomosis. METHODS: All the materials
      used for this training were commercially available. We selected a boxed machine,
      which can produce pulsatile movements of artificial vessels, and on its roof, we
      installed a two-dimensional home video camera and a monitor. A multiple-holed
      plate was placed in front of the machine, and through these holes, a trainee
      inserted endoscopic surgical instruments and anastomosed the artificial vessels
      by running fashion while watching the monitor. This training program has four
      stages. During the first stage, a trainee has to demonstrate mastery in
      conducting a conventional off-pump coronary artery anastomosis without
      assistance. The second stage is the "nonbeating" version, and the third stage is
      the "beating" version with the model mentioned previously. After a trainee gets
      accustomed to the third stage, the original artificial vessel is replaced with an
      extremely fragile one, and this is the fourth stage. Our trainee conducted one
      hundred fourth-stage anastomoses and each procedure was recorded with the video
      camera. We analyzed several factors from the videos and evaluated the efficacy of
      the training method. We compared the outcomes of the first 50 consecutive
      anastomoses with the following 50 ones and described the learning curves.
      RESULTS: The comparison showed a significant decrease in anastomotic time and
      vessel injury. We considered the quality of anastomosis acceptable after 47
      anastomoses, and anastomotic time fell below 15 minutes at the 81st training at
      the fourth stage. CONCLUSIONS: Our dry-lab system might be an effective training
      method for endoscopic coronary anastomosis.

PMID- 29028654
TI  - To the Editor.

PMID- 29028655
TI  - Potency of HIV-2-specific antibodies increase in direct association with loss of
      memory B cells.
AB  - : Potent HIV-neutralizing antibodies are critical for vaccination and viral
      reservoir control. High levels of neutralizing antibodies characterize HIV-2
      infection, a naturally occurring model of attenuated HIV disease with low-to
      undectable viremia. We found that HIV-2-specific antibody potency increased in
      direct association with the loss of both switched and unswitched memory B cells
      in untreated HIV-2 infection. Thus, HIV antibody affinity maturation is linked to
      memory B-cell exhaustion even in reduced viremia settings.

PMID- 29028657
TI  - Combinations of interventions to achieve a national HIV incidence reduction goal:
      insights from an agent-based model.
AB  - OBJECTIVE: Analyzing HIV care service targets for achieving a national goal of a
      25% reduction in annual HIV incidence and evaluating the use of annual HIV
      diagnoses to measure progress in incidence reduction. DESIGN: Because there are
      considerable interactions among HIV care services, we model the dynamics of
      'combinations' of increases in HIV care continuum targets to identify those that
      would achieve 25% reductions in annual incidence and diagnoses. METHODS: We used
      Progression and Transmission of HIV/AIDS 2.0, an agent-based dynamic stochastic
      simulation of HIV in the United States. RESULTS: A 25% reduction in annual
      incidence could be achieved by multiple alternative combinations of percentages
      of persons with diagnosed infection and persons with viral suppression including
      85 and 68%, respectively, and 90 and 59%, respectively. The first combination
      corresponded to an 18% reduction in annual diagnoses, and infections being
      diagnosed at a median CD4 cell count of 372 cells/MUl or approximately 3.8 years
      from time of infection. The corresponding values on the second combination are
      4%, 462 cells/MUl, and 2.0 years, respectively. CONCLUSION: Our analysis provides
      policy makers with specific targets and alternative choices to achieve the goal
      of a 25% reduction in HIV incidence. Reducing annual diagnoses does not equate to
      reducing annual incidence. Instead, progress toward reducing incidence can be
      measured by monitoring HIV surveillance data trends in CD4 cell count at
      diagnosis along with the proportion who have achieved viral suppression to
      determine where to focus local programmatic efforts.

PMID- 29028658
TI  - Immunologic response to antiretroviral therapy by age among treatment-naive
      patients in Sub-Saharan Africa.
AB  - OBJECTIVE: To estimate the association between age at antiretroviral therapy
      (ART) initiation and immunologic response over time by stratum of baseline CD4
      cell counts. DESIGN: Retrospective cohort analysis of data pooled from four
      President's Emergency Plan for AIDS Relief funded countries in Sub-Saharan
      Africa. METHODS: General linear models were used to estimate the mean CD4 cell
      count by age group within groups defined by baseline CD4 cell count. Kaplan-Meier
      methods were used to estimate time to achieving a CD4 cell count of at least 500
      cells/MUl by age group and stratified by baseline CD4 cell count. RESULTS: A
      total of 126 672 previously treatment-naive patients provided 466 482 repeated
      CD4 cell count measurements over 4 years of ART. The median baseline CD4 cell
      count for all age groups was less than 200 cells/MUl. Patients aged 30-39, 40-49,
      50-59, and 60 and older at ART initiation had significantly lower mean CD4 cell
      counts in most strata and at most time points than those 20-29 years old.
      Compared with those 20-29, all older age groups had a significantly longer time
      to, and lower rate of, achieving a CD4 cell count of 500 cells. CONCLUSION: Age
      is associated with the magnitude of CD4 cell gain and the amount of time it takes
      to gain cells at different levels of baseline CD4 cell count. The delay in
      achieving a robust immune response could have significant implications for the
      risk of tuberculosis reactivation as well as comorbidities associated with age in
      the management of older HIV-infected patients.

PMID- 29028659
TI  - Differences in acute retroviral syndrome by HIV-1 subtype in a multicentre cohort
      study in Africa.
AB  - OBJECTIVE: Symptoms of acute retroviral syndrome (ARS) may be used to identify
      patients with acute HIV-1 infection who seek care. ARS symptoms in African adults
      differ by region. We assessed whether reporting of ARS was associated with HIV-1
      subtype in a multicentre African cohort study representing countries with
      predominant HIV-1 subtypes A, C, and D. METHODS: ARS symptoms were assessed in
      adults enrolling within 6 weeks after the estimated date of infection in an acute
      and early HIV-1 infection cohort study. HIV-1 subtype was determined by POL
      genotyping. We used log-binomial regression to compare ARS symptom prevalence
      among those with subtype A vs. C or D, adjusting for sex, time since enrolment,
      and enrolment viral load. RESULTS: Among 183 volunteers ascertained within 6
      weeks after estimated date of infection, 77 (42.0%) had subtype A, 83 (45.4%)
      subtype C, and 23 (12.6%) subtype D infection. Individuals with subtype A were
      1.40 (95% confidence interval: 1.17, 1.68) times as likely as individuals with
      subtypes C or D to report any ARS symptoms; each individual symptom other than
      rash was also more prevalent in subtype A than in subtype C or D, with prevalence
      ratios ranging from 1.94 (1.40, 2.70) for headache to 4.92 (2.24, 10.78) for
      lymphadenopathy. CONCLUSION: Individuals with subtype A were significantly more
      likely than individuals with subtypes C or D to report any ARS symptoms. HIV-1
      subtypes may help explain differences in ARS that have been observed across
      regions in Africa, and may impact the yield of symptom-based screening strategies
      for acute HIV infection detection.

PMID- 29028660
TI  - Cumulative exposure of TDF is associated with kidney tubulopathy whether it is
      currently used or discontinued.
AB  - OBJECTIVE: Tenofovir disoproxil fumarate (TDF) increases the risk of kidney
      tubular dysfunction (KTD). This study was conducted to elucidate whether KTD
      persists after discontinuation of TDF. DESIGN: A prospective cross-sectional
      study which enrolled 941 HIV-1-infected patients. METHODS: KTD was predefined as
      the presence of at least two abnormalities among the five tubular markers
      (fractional excretion of phosphate, fractional excretion of uric acid, beta2
      microglobulinuria, N-acetyl-beta-D-glucosaminidase, nondiabetic glycosuria).
      Logistic regression model was used to examine the association between KTD and
      cumulative TDF use, as well as current status of TDF use. RESULTS: In total, 94%
      of study patients were men (median age 45, estimated glomerular filtration rate
      75 ml/min per 1.73 m, CD4 575 cells/MUl. About 98% were on antiretroviral
      therapy. In total, 64% of the patients ever used TDF and 39% currently used TDF.
      Twenty-nine percent used TDF for more than 5 years. KTD was diagnosed in 116
      (12%) patients. In multivariate model, more than 5 years of TDF exposure and
      current TDF use [odds ratio (OR) 4.2, 95% confidence interval (CI) 2.37-7.56],
      more than 5 years and past TDF use (OR 2.4, 95% CI 1.09-5.33), less than 5 years
      and current TDF (OR 2.4, 95% CI 1.24-4.85), and less than 5 years and past TDF
      (OR 2.4, 95% CI 1.22-4.64) were all significantly associated with KTD, with never
      TDF use as reference. The results were the same using 4 and 3 years of exposure
      as the cutoff. However, with 2 years exposure, both less than 2 years and current
      TDF (OR 2.3, 95% CI 0.84-6.20) and less than 2 years and past TDF (OR 1.9, 95% CI
      0.73-4.93) were not associated with KTD, whereas both more than 2 years and
      current TDF and more than 2 years and past TDF were associated. CONCLUSION: The
      association between cumulative TDF use and KTD was strong and robust. The results
      of the study suggested that TDF-related KTD might persist after discontinuation
      of TDF if patients used TDF for more than 2 years.

PMID- 29028661
TI  - Changes in viral suppression status among US HIV-infected patients receiving
      care.
AB  - OBJECTIVE: To examine changes in viral suppression status among HIV patients
      receiving care in 2014 and the extent of viral suppression among persons with
      infrequent care visits. METHODS: Using data reported to the National HIV
      Surveillance System from 33 jurisdictions with complete reporting of CD4 and
      viral load tests, we created four viral suppression status groups based on their
      first and last viral loads in 2014: both suppressed, first unsuppressed and last
      suppressed (improved), first suppressed and last unsuppressed (worsened), and
      both unsuppressed. We also calculated the number and percentage of persons whose
      sole viral load in 2014 was suppressed and had a suppressed viral load at their
      last test in 2013. RESULTS: Among 339 515 persons with at least two viral load
      tests in 2014, 72.6% had all viral loads suppressed (durably suppressed); 75.5%
      had the first and last tests suppressed, 10.5% improved, 4.2% worsened, and 9.9%
      had both unsuppressed. Among 92 309 persons who had only one viral load test in
      2014, 69 960 (75.8%) were suppressed and, of those, 53 834 (76.9%) also had a
      suppressed viral load at their last test in 2013. CONCLUSION: National
      surveillance data show that the majority of patients in HIV care during 2014 were
      durably suppressed. More showed improved compared with worsened viral suppression
      status. Some patients who have less frequent care visits have sustained viral
      suppression. Yet one in 10 who was in regular care did not have a suppressed
      viral load in 2014, indicating missed opportunities for clinical interventions to
      help patients achieve and sustain viral suppression.

PMID- 29028663
TI  - Chronically infected T-cell lines become handy for a novel assay measuring the
      reservoir of replication-competent HIV-1.

PMID- 29028662
TI  - Stool Xpert MTB/RIF and urine lipoarabinomannan for the diagnosis of tuberculosis
      in hospitalized HIV-infected children.
AB  - BACKGROUND: Tuberculosis (TB) causes substantial morbidity and mortality in HIV
      infected children. Sample collection and the paucibacillary nature of TB in
      children makes diagnosis challenging. Rapid diagnostic tools using easily
      obtained specimens are urgently needed. METHODS: Hospitalized, HIV-infected
      children aged 12 years or less enrolled in a randomized controlled trial
      (NCT02063880) comparing urgent to post-stabilization antiretroviral therapy
      initiation in Kenya underwent TB evaluation. At enrollment, sputum or gastric
      aspirates were collected for TB culture and Xpert, stool for Xpert, and urine for
      lipoarabinomannan (LAM). When possible, a second sputum/gastric aspirate for
      culture was obtained. Stool Xpert and urine LAM performance were compared to
      reference sputum/gastric aspirate culture. RESULTS: Among 165 HIV-infected
      children, median age was 24 months [interquartile range (IQR) 13-58], median CD4%
      was 14.3 (IQR 8.9-22.0%), and 114 (69.5%) had severe immunosuppression. Thirteen
      (7.9%) children had confirmed TB (positive culture and/or Xpert). Sputum/gastric
      aspirate Xpert, stool Xpert, and urine LAM sensitivities were 60% [95% confidence
      interval (CI) 26-88%], 63% (95% CI 25-92%), and 43% (95% CI 10-82%),
      respectively. Specificity was 98% (95% CI 94-100%) for sputum/gastric aspirate
      Xpert, 99% (95% CI 95-100%) for stool Xpert, and 91% (95% CI 84-95%) for urine
      LAM. Stool Xpert and urine LAM sensitivity increased among children with severe
      immunosuppression [80% (95% CI 28-100) and 60% (95% Cl 15-95%)]. CONCLUSION:
      Stool Xpert had similar performance compared with sputum/gastric aspirate Xpert
      to detect TB. Urine LAM had lower sensitivity and specificity, but increased
      among children with severe immunosuppression. Stool Xpert and urine LAM can aid
      rapid detection of TB in HIV-infected children using easily accessible samples.

PMID- 29028664
TI  - Abacavir use and risk of recurrent myocardial infarction.
AB  - OBJECTIVE: To investigate the association between abacavir (ABC) use and
      recurrent myocardial infarction (MI) among HIV-positive people with a prior MI.
      DESIGN: International multicohort collaboration with follow-up from 1999 to 2016.
      METHODS: The rate of recurrent MI was described among D:A:D participants who
      experienced an index MI whilst in the study, and who remained under follow-up
      beyond 28 days after this MI. Follow-up was considered to the date of next MI,
      death, 1 February 2016 or 6 months after last clinic visit. Poisson regression
      models considered associations between recurrent MI and exposure to ABC (use at
      index MI, current post-MI exposure and cumulative exposure), before and after
      adjusting for calendar year. RESULTS: The 984 individuals who experienced an
      index MI during the study (91.3% male, median age 51 at index MI) were followed
      for 5312 person-years, over which time there were 136 recurrent MIs (rate
      2.56/100 person-years, 95% confidence interval 2.13-2.99). Rates were 2.40 (1.71
      3.09) and 2.65 (2.10-3.21)/100 person-years in those who were and were not on
      ABC, respectively, at the index MI, and 2.90 (2.01-3.78) and 2.44 (1.95-2.93)/100
      person-years in those who were and were not currently receiving ABC,
      respectively, post-MI. No association was seen with recurrent MI and either
      cumulative exposure to ABC [relative rate 0.86 (0.68-1.10)/5 years], receipt of
      ABC at index MI [0.90 (0.63-1.29)] nor recent post-MI exposure to ABC [1.19 (0.82
      1.71)]. CONCLUSION: Among people with a previous MI, there was no evidence for an
      association between use of ABC post-MI and an elevated risk of a recurrent MI.

PMID- 29028665
TI  - Gynecologic cancer in HIV-infected women: treatment and outcomes in a multi
      institutional cohort.
AB  - OBJECTIVE: To evaluate gynecologic cancer treatments in HIV-infected women for
      adherence to National Comprehensive Cancer Network (NCCN) guidelines and to
      describe survival by adherence to guidelines. DESIGN: Beyond cervical cancer,
      there are little data on treatment and outcomes for these women. This is a
      retrospective cohort study of HIV-infected women with gynecologic cancers.
      METHODS: HIV-infected women with gynecologic cancers from 2000 to 2015 were
      identified at two urban, comprehensive cancer centers. Chart reviews extracted
      demographic, HIV, and cancer-related variables. Cancer treatment was evaluated
      for adherence to NCCN guidelines. Overall survival was compared between those who
      received NCCN adherent and nonadherent cancer care. RESULTS: Fifty-seven women
      were identified; 15 vulvar (26%), 26 cervical (46%), nine ovarian (16%), and
      seven endometrial (12%) cancers. Median time from HIV to cancer diagnosis was 8.5
      years, and 88% of women were black. Thirty patients (53%) had stage I, and 27
      (47%) had stage II-IV disease. Overall, 28 women (49%) received NCCN-adherent
      care; 22 of 30 stage I (73%) and six of 27 stage II-IV patients (22%). Among 29
      women not receiving NCCN-adherent care, 69% were due to patient-related factors
      or toxicity. Among women with II-IV cancers, 48-month survival was higher in
      women who received NCCN-adherent care than those who did not (60 versus 28%).
      CONCLUSION: Most HIV-infected women with advanced gynecologic cancers did not
      receive NCCN-adherent care and had worse survival compared to those who did.
      Focus on treatment-related toxicities and patient-related barriers to cancer care
      are necessary in this population.

PMID- 29028666
TI  - Microbial translocation: translating simian immunodeficiency virus to HIV.
AB  - PURPOSE OF REVIEW: The article describes recent advances in understanding the
      causes and consequences of microbial translocation in HIV and simian
      immunodeficiency virus infections. RECENT FINDINGS: Persistent microbial
      translocation contributes to aberrant immune activation in immunodeficiency
      lentiviral infections and thereby, pathogenesis and mortality. Efforts to
      delineate the circumstances surrounding translocation have benefited from use of
      simian immunodeficiency virus-infected nonhuman primates and highlight the
      overwhelming immunologic diversion caused by translocating microbes. The use of
      therapeutics aimed at reducing microbial translocation show promise and will
      benefit from continued research into the mechanisms that promote systemic
      microbial dissemination in treated and untreated infections. SUMMARY: Insights
      into the source and identity of translocating microbes in lentiviral infections
      continue to enhance the development of adjunct therapeutics.

PMID- 29028668
TI  - The mycobiome in HIV.
AB  - PURPOSE OF REVIEW: There are a limited number of studies investigating the
      association between the microbiome and HIV. Although the majority of these
      published investigations have focused on the role of the bacterial community
      (bacteriome) in this setting, a handful of studies have also characterized the
      role of the mycobiome in HIV-infected individuals. This review will summarize the
      most recent reports pertaining to the role of the fungal community in HIV. RECENT
      FINDINGS: Differences in the composition of the oral and respiratory mycobiome in
      HIV-infected individuals compared with uninfected individuals have been reported.
      SUMMARY: Our review shows that studies investigating the role of the mycobiome in
      the setting of HIV are severely lacking. With recent advances in our
      understanding of the composition of the human microbiome, investigations into the
      role of the bacteria and fungus comprising the overall microbiota and how the two
      interact to influence each other and the host is crucial.

PMID- 29028669
TI  - The Fourth Conference of the International Society for Environmental Epidemiology
      in the Asia Chapter Region.

PMID- 29028667
TI  - Impact of antiretroviral drugs on the microbiome: unknown answers to important
      questions.
AB  - PURPOSE OF REVIEW: Little is known on how different antiretroviral (ARV) drugs
      affect the gut microbiome in HIV infection; and conflicting data exists on the
      effect of ARV drugs on residual inflammation/immune activation and microbial
      translocation. RECENT FINDINGS: Gut microbiome involvement in the transmission
      and pathogenesis of HIV infection is increasingly being recognized. Various
      studies have shown that antiretroviral therapy (ART) is unable to restore gut
      health despite effective suppression of plasma HIV viremia. Indeed, the
      resolution of residual inflammation and gut microbial translocation is partial
      under ART. Very recent studies have provided new evidence that ARV combinations
      can differentially affect the gut microbiome, immune activation and microbial
      translocation. Furthermore, a recent article uncovered a link between drug
      metabolism and specific microbial species indicating that microbes can directly
      metabolically degrade ARV drugs when administered topically. SUMMARY: There are
      still many unanswered questions regarding ARVs and the gut microbiome. It is,
      therefore, critical for researchers to address the effect of distinct ARV drugs
      on the microbiome and vice versa: the effects of the microbiome on ARV drug
      metabolism, and speculate about possible therapeutic avenues.

PMID- 29028670
TI  - Cord Blood Bisphenol A Levels and Reproductive and Thyroid Hormone Levels of
      Neonates: The Hokkaido Study on Environment and Children's Health.
AB  - BACKGROUND: Bisphenol A (BPA) is widely used and BPA exposure is nearly
      ubiquitous in developed countries. While animal studies have indicated adverse
      health effects of prenatal BPA exposure including reproductive dysfunction and
      thyroid function disruption possibly in a sex-specific manner, findings from
      epidemiologic studies have not been enough to prove these adverse effects. Given
      very limited research on human, the aim of this study was to investigate
      associations between cord blood BPA levels and reproductive and thyroid hormone
      levels of neonates and whether associations differed by neonate sex. METHODS: The
      study population included 514 participants of the Hokkaido study recruited from
      2002 to 2005 at one hospital in Sapporo, Japan. The BPA level in cord blood was
      determined by ID-LC/MS/MS, and the limit of quantification was 0.040 ng/ml. We
      measured nine types of reproductive hormone levels in cord blood, and thyroid
      hormone levels were obtained from neonate mass screening test data. There were
      283 subjects, who had both BPA and hormone levels measurements, included for the
      final analyses. RESULTS: The geometric mean of cord blood BPA was 0.051 ng/ml.
      After adjustment, BPA level was negatively associated with prolactin (PRL) (beta
      = -0.38). There was an interaction between infant sex and BPA levels on PRL; a
      weak negative association was found in boys (beta = -0.12), whereas a weak
      positive association was found in girls (beta = 0.14). BPA level showed weak
      positive association with testosterone, estradiol, and progesterone levels in
      boys. No association was found between BPA and thyroid hormone levels.
      CONCLUSIONS: Our findings suggested that fetal BPA levels might be associated
      with changes in certain reproductive hormone levels of neonates in a sex-specific
      manner, though further investigations are necessary.

PMID- 29028671
TI  - Prenatal and Childhood Exposure to Phthalate Diesters and Thyroid Function in a 9
      Year Follow-up Birth Cohort Study: Taiwan Maternal and Infant Cohort Study.
AB  - BACKGROUND: Phthalates are widely used in industry, personal care products, and
      medications. Recent studies have suggested that phthalate exposure alters thyroid
      hormones. However, longitudinal studies concerning the association between
      phthalate exposure and thyroid function in children are scant. Therefore, we
      examined the association between pre- and postnatal phthalate exposure and
      thyroid function in children born in 2000-2001. METHODS: We studied 181 mother
      child pairs in central Taiwan and followed-up the children from 2000 to 2009 at
      2, 5, and 8 years old. We measured serum levels of thyroxine (T4), free T4,
      triiodothyronine (T3), and thyroid-stimulating hormone in children by using
      radioimmunoassay. We quantified seven phthalate metabolites, representing the
      five most commonly used phthalates, in maternal and child urine samples by using
      liquid chromatography-tandem mass spectrometry. The metabolites were
      monoethylhexyl phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP),
      mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) derived from di(2-ethylhexyl)
      phthalate (DEHP), monomethyl phthalate (MMP), monoethyl phthalate (MEP),
      monobutyl phthalate (MBP), and monobenzyl phthalate (MBzP). We constructed a
      linear mixed model to examine these associations after adjustments for
      covariates. RESULTS: The T4 levels were inversely associated with maternal
      urinary MEHHP (beta = -0.028 [95% confidence interval (CI) = -0.051, -0.006]) and
      MEOHP (beta = -0.027 [-0.050, -0.003]), with similar T3 levels being observed in
      boys, even when the children exposure levels were considered spontaneously. In
      the girls, the free T4 levels were inversely associated with levels of maternal
      urinary MEP (beta = -0.042), maternal urinary MBzP (beta = -0.050), and
      children's urinary MEHP (beta = -0.027). CONCLUSIONS: Early life phthalate
      exposure was associated with decreased thyroid hormone levels in young children.

PMID- 29028672
TI  - Birth Cohort Consortium of Asia: Current and Future Perspectives.
AB  - BACKGROUND: The environmental health of children is one of the great global
      health concerns. Exposures in utero and throughout development can have major
      consequences on later health. However, environmental risks or disease burdens
      vary from region to region. Birth cohort studies are ideal for investigating
      different environmental risks. METHODS: The principal investigators of three
      birth cohorts in Asia including the Taiwan Birth Panel Study (TBPS), the Mothers
      and Children's Environmental Health Study (MOCEH), and the Hokkaido Study on
      Environment and Children' Health (Hokkaido Study) coestablished the Birth Cohort
      Consortium of Asia (BiCCA) in 2011. Through a series of five PI meetings, the
      enrolment criteria, aim of the consortium, and a first-phase inventory were
      confirmed. RESULTS: To date, 23 birth cohorts have been established in 10 Asian
      countries, consisting of approximately 70,000 study subjects in the BiCCA. This
      article provides the study framework, environmental exposure and health outcome
      assessments, as well as maternal and infant characteristics of the participating
      cohorts. CONCLUSIONS: The BiCCA provides a unique and reliable source of birth
      cohort information in Asian countries. Further scientific cooperation is ongoing
      to identify specific regional environmental threats and improve the health of
      children in Asia.

PMID- 29028673
TI  - Association Between Organophosphate Pesticide Exposure and Thyroid Hormones in
      Pregnant Women.
AB  - BACKGROUND: Use of organophosphate pesticides (OPs) is widespread in China.
      Although animal studies suggested that OP exposure could affect thyroid function,
      little is explored in human populations. METHODS: We investigated levels of OP
      exposure in pregnant women and the relationship between OPs and thyroid hormones
      in Shandong, China. We enrolled 637 pregnant women from April 2011 to December
      2013. OP exposure was assessed by a questionnaire administered to the pregnant
      women in the hospital and by analyses of urinary dialkylphosphate (DAP)
      metabolites of OPs in pregnant women (n = 413). We measured the concentration of
      five thyroid hormones in serum samples in pregnant women (n = 325) and analyzed
      the association between DAP metabolites of OPs and thyroid hormones (n = 325).
      RESULTS: Median levels of DAP metabolites were 9.81 MUg/L for dimethylphosphate
      (DMP), 0.79 MUg/L for dimethylthiophosphate (DMTP), 5.00 MUg/L for
      diethylphosphate (DEP), and 0.78 MUg/L for diethylthiophosphate (DETP), which
      were higher than those reported in developed countries. We found that the total
      DAP concentration (the sum of DMP, DMTP, DEP, and DETP) in urine was positively
      associated with free T4 levels (beta = 0.137; 95% confidence interval [CI] =
      0.012, 0.263) and negatively associated with thyroid-stimulating hormone levels
      (beta = -0.145; 95% CI = -0.242, -0.048). CONCLUSIONS: The findings suggest that
      OP exposure may be associated with changes in thyroid function in pregnant women.
      Given that urinary OP levels in pregnant women in Shandong were much higher than
      those reported in developed countries, further studies on the effects of OP
      exposure on thyroid function in pregnant women in China are warranted.

PMID- 29028674
TI  - Urinary Bisphenol A Concentration and Gestational Diabetes Mellitus in Chinese
      Women.
AB  - BACKGROUND: Bisphenol A (BPA) has been associated with variable metabolic effects
      in animal models. It is unknown whether BPA exposure affects glucose tolerance in
      pregnancy. We aimed to investigate whether maternal urinary BPA concentration is
      associated with gestational diabetes mellitus (GDM). METHODS: This study included
      620 pregnant women from Shanghai, China 2012-2013. Maternal urinary BPA
      concentration was measured by high-performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS). GDM (n = 79) was diagnosed according to the criteria
      of the International Association of Diabetes and Pregnancy Study Groups (IADPSG).
      Multivariate regressions were used to explore the relationships of urinary BPA
      with GDM, plasma glucose levels in the 75-g 2-hour oral glucose tolerance test
      (OGTT), birth weight, and ponder index. RESULTS: The geometric mean of BPA was
      1.32 MUg/L. After adjustment for maternal age, education, husband smoking status,
      prepregnancy body mass index (BMI), and urinary creatinine concentration, plasma
      glucose at 2 hours in the 75-g OGTT was 0.36 mmol/L lower (95% confidence index
      [CI] = -0.73, 0.01) for women with urine BPA in the high versus the low tertile.
      For each unit increase in natural log-transformed BPA, the odds of GDM was
      reduced by 27% (odds ratio (OR) = 0.73; 95% CI = 0.56, 0.97), the birth weight
      decreased by 25.70 g (95% CI = -54.48, 3.07), and ponder index was decreased by
      0.02 (100 g/cm) (95% CI = -0.03, 0.00). CONCLUSIONS: Higher maternal urinary BPA
      concentrations were associated with reduced risk of GDM and marginally lower
      birth weight and ponder index.

PMID- 29028675
TI  - The Risk of Stroke in Physicians: A Population-based Cohort Study in Taiwan.
AB  - BACKGROUND: Physicians in Taiwan work in stressful workplaces and have heavy
      workloads, both of which may contribute to the occurrence of a stroke. However,
      it is not clear whether they have a higher risk of stroke. Therefore, we
      conducted a population-based cohort study to compare the risks of stroke between
      physicians and the general population and among subgroups of physicians in
      Taiwan. METHODS: In the National Health Insurance Research Database of Taiwan, we
      identified 28,062 physicians and selected 84,186 age- and sex-matched nonmedical
      staff beneficiaries as the references. Using conditional logistic regression, we
      compared the prevalence of stroke between physicians and references. In addition,
      we made comparisons among subgroup of physicians defined by age, sex,
      comorbidity, specialty, and the level of hospital. RESULTS: During the study
      period, physicians had higher prevalence rates of hypertension (23.6% vs. 19.1%),
      hyperlipidemia (21.4% vs. 12.9%), and coronary artery disease (CAD) (6.4% vs.
      5.7%) than the referent group, but they had a lower risk of stroke with an odds
      ratio of 0.61 (95% confidence interval = 0.55, 0.66) after adjusting for
      hypertension, diabetes, hyperlipidemia, CAD, and active worker. Among physicians,
      the risks were higher in those who were older or had hypertension, diabetes,
      hyperlipidemia, or CAD. CONCLUSIONS: Despite having higher prevalence rates of
      hypertension, hyperlipidemia, and CAD and working in stressful workplaces with
      heavy workloads, our study suggests that physicians in Taiwan have a lower risk
      of stroke compared with the general population. These results may indicate the
      benefits of higher awareness and more knowledge of diseases.

PMID- 29028676
TI  - Air Pollution as a Potential Determinant of Rheumatoid Arthritis: A Population
      based Cohort Study in Taiwan.
AB  - BACKGROUND: Limited studies have explored the relationship between air pollution
      and rheumatoid arthritis (RA), with the results being somewhat inconsistent.
      METHODS: This was a retrospective cohort study that included 322,301 subjects
      aged 30-50 years, selected from the National Health Insurance Research Database
      in Taiwan, were followed from 2001 to 2010. We used a time-dependent extended Cox
      model and incorporated time-dependent variables to estimate the associations
      between the annual mean concentrations of air pollutants with RA, including
      carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), particles with an
      aerodynamic diameter less than 10 MUm (PM10), and sulfur dioxide (SO2), and
      reported the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Newly
      diagnosed RA was positively associated with a 100-ppb increase in CO (adjusted HR
      = 1.17 [95% CI = 1.16, 1.18]), a 10-ppb increase in NO2 (1.54 [1.45, 1.64]), a 10
      ppb increase in O3 (1.37 [1.33, 1.41]), and a 1 ppb in SO2 (1.02 [1.00, 1.04]).
      There was no association between a 10-MUg/m increase in PM10 and RA (1.02 [0.99,
      1.05]). CONCLUSIONS: Our finding suggests that O3 and traffic-related air
      pollutants (CO and NO2) may be positively associated with incident RA. This is an
      important finding given that many individuals are exposed to similar levels of O3
      and NO2 globally.

PMID- 29028677
TI  - Are People With a History of Disease More Susceptible to a Short-term Exposure to
      Asian Dust?: A Case-Crossover Study Among the Elderly in Japan.
AB  - BACKGROUND: Factors influencing the susceptibility of the elderly to the adverse
      health effects of short-term exposure to desert dust have yet to be explored. We
      aimed to identify the disease histories that increase the susceptibility of the
      elderly to disease onset induced by dust events. METHODS: We used a time
      stratified case-crossover design using data on 17,874 elderly residents (>=65
      years) of Okayama, Japan, who were transported to hospital emergency rooms
      because of cardiovascular and respiratory diseases between 2006 and 2010. We used
      conditional logistic models to calculate the odds ratios (ORs) per interquartile
      increase of Asian dust. We then conducted stratified analyses based on patients
      with or without a history of chronic disease. RESULTS: Dust concentration was
      associated with a higher risk of cardiovascular (3-day lag), cerebrovascular
      (same day), and respiratory (3-day lag) disease onset. Patients with a history of
      respiratory disease had a higher risk of cardiovascular (OR: 1.09 [95% confidence
      interval (CI) = 1.00, 1.19] vs. 0.99 [0.97, 1.01]; P for interaction = 0.03) or
      cerebrovascular (1.15 [1.01, 1.31] vs. 0.99 [0.97, 1.01]; P = 0.02) disease onset
      (2-day lag) than those without. Patients with diabetes also had a higher risk of
      cerebrovascular disease onset (1.09 [1.00, 1.19] vs. 0.99 [0.97, 1.01]; P = 0.05)
      (2-day lag). In contrast, patients with a history of cerebrovascular disease had
      a lower risk of respiratory disease. CONCLUSIONS: People with a history of
      respiratory disease or diabetes might have a greater susceptibility to
      cardiovascular disease from Asian dust and would therefore benefit from proactive
      interventions during desert dust events.

PMID- 29028678
TI  - Increase in Medical Emergency Calls and Calls for Central Nervous System Symptoms
      During a Severe Air Pollution Event, January 2013, Jinan City, China.
AB  - BACKGROUND: In January 2013, a continuous and severe haze event affected one
      third of the major cities in China, including Jinan. OBJECTIVES: We investigated
      whether medical emergency calls (for nonaccidental emergencies) and calls for
      Central Nervous System (CNS) syndromes increased during this episode compared
      with the previous winter months (January, February, and December) in 2011 and
      2012. METHODS: Daily emergency calls were obtained from Jinan Medical Emergency
      Center. Sentinel CNS syndromes from nonaccidental emergency calls included seven
      symptoms: headache, dizziness, syncope, coma, convulsions, paralysis, and
      epilepsy. Particles with aerodynamic diameter <10 um (PM10) were used as the
      indicator of air pollution. A generalized linear model based on quasi-Poisson
      regression was used to evaluate the effects on nonaccidental emergency calls and
      calls for CNS syndromes and each symptom, separately, during this episode.
      RESULTS: Markedly higher mean daily concentration, 332 MUg/m of PM10, during this
      episode versus reference months was found. Obviously increased effects on
      nonaccidental emergency calls and calls for CNS syndromes were observed during
      this episode, with relative risk (RR) value 1.3 (95% CI = 1.2, 1.3) and 1.2 (95%
      CI = 1.1, 1.3). Four of seven CNS symptoms were also increased during this
      episode: RRs values for dizziness, convulsions, paralysis, and epilepsy were 1.4
      (95% CI = 1.2, 1.7), 1.4 (95% CI = 1.1, 1.6), 1.6 (95% CI = 1.2, 2.1), and 1.5
      (95% CI = 1.1, 2.0), respectively. CONCLUSIONS: A noticeable increase in medical
      emergency calls and calls for Central Nervous System syndromes were observed
      during a severe air pollution episode on January 2013, in a large Chinese city.

PMID- 29028679
TI  - Association Between Long-term Exposure to Traffic-related Air Pollution and
      Inflammatory and Thrombotic Markers in Middle-aged Adults.
AB  - BACKGROUND: Studies evaluating possible associations between long-term exposure
      to air pollution and inflammatory and thrombotic markers are limited. METHODS:
      From 2009 to 2011, we monitored hematologic parameters and thrombotic markers in
      402 volunteers 35-65 years of age who were recruited as the non-coronary heart
      disease (CHD) controls in a study of work-related factors and CHD in Taipei. We
      applied land-use regression models developed by the European Study of Cohorts for
      Air Pollution Effects to estimate the mean annual exposure of each participant to
      five air pollutants at their residence in Taipei, namely particulate matter (PM)
      of diameter <10 MUm (PM10) and 2.5 MUm (PM2.5), the absorbance of PM2.5 (PM2.5
      abs), nitrogen dioxide (NO2), and nitrogen oxide (NOx). RESULTS: The mean annual
      exposures were 47.82 +/- 4.78 ug/m for PM10, 29.08 +/- 5.10 ug/m for PM2.5, and
      2.04 +/- 0.37 (10 m) for PM2.5 abs. Multivariate linear regression analyses
      showed that the mean percentage (95% confidence interval) of blood monocyte
      counts increased by 9.08% (1.61%, 16.54%) per 10 ug/m increase in PM10, by 16.28%
      (6.66%, 25.89%) per 1.0 * 10 m increase in PM2.5 abs, by 8.28% (2.08%, 14.48%)
      per 20 ug/m increase in NO2, and by 2.84% (1.22%, 4.46%) per 10 ug/m increase in
      NOx. In addition, each 5 MUg/m increase in PM2.5 was associated with 1.97%
      (0.02%, 3.92%) increases in fibrinogen. CONCLUSIONS: Long-term exposure to
      traffic-related air pollution is positively associated with subclinical
      inflammatory and thrombotic markers in middle-aged workers in Taipei.

PMID- 29028680
TI  - Association Between Dioxin and Metabolic Syndrome by Age and Sex in an Endemic
      Area of Exposure in Taiwan.
AB  - BACKGROUND: Some of the effects of dioxins seem to be different between men and
      women, and exposures starting at an early age seem to have more prominent
      effects. Therefore, we conducted a study in Taiwan to evaluate the associations
      between exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs)
      and metabolic syndrome (MetS) starting at different ages in both sexes. METHODS:
      We recruited participants from an area where residents were exposed to PCDD/Fs
      released from a factory and defined serum PCDD/Fs levels >=20 pg WHO98-TEQDF/g
      lipid as high dioxin levels. MetS was defined as meeting three of the following
      criteria: fasting glucose >=100 mg/dl or under treatment for diabetes, waist
      circumference >=90 cm in men or >=80 cm in women, triglycerides >=150 mg/dl or
      under treatment for elevated triglycerides, high-density lipoprotein <40 mg/dl in
      men or <50 mg/dl in women, and blood pressures >=130/85 mmHg or under treatment
      for hypertension. RESULTS: Of the 2758 participants, 785 patients with MetS were
      identified, and we observed positive associations between a high dioxin level and
      MetS. After adjusting for sex, age, and age at starting exposure, we found that a
      high dioxin level was an independent predictor for MetS (adjusted odds ratio
      =1.38; 95% confidence interval = 1.11, 1.72). When we stratified the participants
      by gender, we found that a high dioxin level remained an independent predictor of
      MetS in men, but not in women, regardless of the age at starting exposure.
      CONCLUSIONS: Exposure to PCDD/Fs was associated with MetS in men, independent of
      age and age at starting exposure.

PMID- 29028681
TI  - Polybrominated Diphenyl Ether Concentrations in Human Breast Milk Specimens
      Worldwide.
AB  - BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are a class of flame
      retardants of ubiquitous presence in numerous consumer products. PBDEs may impair
      neurodevelopment in infants. There is a lack of meta-analysis on PBDE
      concentrations in human breast milk worldwide. We aimed to summarize global
      research data on PBDE concentrations in human breast milk specimens in recent
      years. METHODS: We conducted a systematic review through PubMed search of
      original studies on PBDE concentrations in human individual breast milk specimens
      collected in the general population over the recent 15-year period (2000-2015)
      worldwide. RESULTS: A total of 49 eligible studies (total number of study
      subjects = 7,502) were identified. The pooled means (95% CI) of total PBDE
      concentration in breast milk (ng/g lipid) were 66.8 (44.7, 88.9) in North
      America, 2.6 (2.2, 3.1) in Europe, and 2.8 (2.4, 3.3) in Asia, respectively. The
      pooled means (95% CI) of median total PBDEs concentration in breast milk (ng/g
      lipid) were 40.0 (30.8-49.1) in North America, 1.9 (1.4-2.4) in Europe, and 2.2
      (1.3-3.2) in Asia. The high concentrations of total PBDEs in breast milk in North
      America were mainly due to high concentrations of brominated diphenyl ether-47
      (BDE-47), BDE-99, BDE-100, and BDE-153. There were too few studies from other
      continents (Africa, South America, and Oceania) for meaningful meta-analysis.
      CONCLUSION: Total PBDE concentrations in breast milk in the recent 15-year period
      were over 20 times higher in North America versus Asia or Europe, and comparable
      in Europe versus Asia. There is a need for more research data from other
      continents.

PMID- 29028682
TI  - Current and Projected Burden of Disease From High Ambient Temperature in Korea.
AB  - BACKGROUND: The objective of the present study was to estimate the current and
      projected burden of disease from high ambient temperature using population-based
      data sources of nationwide mortality and morbidity in Korea. METHODS: Disability
      adjusted life years (DALY) were estimated using noninjury-related deaths, and
      cerebrovascular and cardiovascular diseases from recently released nationwide
      health and mortality databases. Years of life lost and years lost due to
      disability were measured based on the point prevalence and number of deaths
      during the study period. Future DALY attributable to heat waves were estimated
      from projected populations, and temperature predictions for the years 2030 and
      2050 were under Representative Concentration Pathways (RCP) 4.5 and 8.5 with
      summertime temperatures above threshold. RESULTS: Relative risks (RR) of total
      mortality and of cardiovascular disease were 1.02 (95% CI, 1.01, 1.02) and 1.08
      (95% CI, 1.06, 1.09) for each 1 degrees C increase in temperature above
      threshold, respectively. The morbidity of heat-related disease was RR 1.67 (95%
      CI, 1.64, 1.68) for each 1 degrees C increase in temperature above threshold.
      DALY for all-cause death were 0.49 DALY/1000 in 2011, 0.71 (0.71) DALY/1000 in
      2030 and 0.77 (1.72) DALY/1000 in 2050 based on RCP 4.5 (RCP 8.5). DALY for
      cardio- and cerebrovascular diseases were 1.24 DALY/1000 in 2011, 1.63 (1.82)
      DALY/1000 in 2030, and 1.76 (3.66) DALY/1000 in 2050 based on RCP 4.5 (RCP 8.5).
      CONCLUSIONS: Future excess mortality due to high ambient temperature is expected
      to be profound in Korea. Efforts to mitigate climate change can provide
      substantial health benefits via reducing heat-related mortality.

PMID- 29028683
TI  - Lung Cancer Associated with Arsenic Ingestion: Cell-type Specificity and Dose
      Response.
AB  - BACKGROUND: Arsenic is a well-documented human carcinogen, and studies on urinary
      and skin cancers have shown that the carcinogenicity of ingested arsenic has cell
      type specificity. To evaluate whether this is also true for lung cancers, we
      conducted a study on 243 townships in Taiwan. METHODS: The arsenic levels were
      assessed using measurement reports from a previous survey, and the incidence of
      lung cancer was assessed using the data gathered by the National Cancer Registry
      Program. We analyzed data by regression models with multiple variables to
      describe exposure levels; each variable denoted the proportion of people in a
      specific exposure category in each township. An urbanization index and variables
      denoting the distribution of age in each township were also included in the model
      to adjust for effects of urbanization and age. RESULTS: Among the three major
      cell types of lung cancer, squamous cell carcinoma appeared to be associated with
      arsenic level in drinking water, and the association was more prominent at
      exposure level above 0.64 mg/L in both men and women. A 1% increase in the
      proportion of wells in this category was associated with an increase of 0.27 per
      100,000 per year in the incidence of squamous cell lung cancer in men and 0.13
      per 100,000 per year in women. Adenocarcinoma and small cell carcinoma were not
      associated with arsenic level in drinking water. CONCLUSIONS: The results
      suggested that the carcinogenicity of arsenic on lungs is cell-type specific,
      which is compatible with observations on urinary and skin cancers. Whereas data
      in the literature were limited, the association between adenocarcinoma and
      arsenic exposures through inhalation appeared to be stronger than that of
      squamous cell carcinoma. Therefore, different exposure routes may give rise to
      different mechanisms in the carcinogenicity of arsenic.

PMID- 29028684
TI  - Toxic Metals Increase Serum Tumor Necrosis Factor-alpha Levels, Modified by
      Essential Elements and Different Types of Tumor Necrosis Factor-alpha Promoter
      Single-nucleotide Polymorphisms.
AB  - BACKGROUND: Lead (Pb), cadmium (Cd), and arsenic (As) could cause health issues
      through oxidative stress that is indicated in the elevated tumor necrosis factor
      alpha (TNF-alpha). However, some of the essential elements-selenium (Se), zinc
      (Zn), cobalt (Co), and copper (Cu)-are cofactors or structural components of
      antioxidant enzymes. It is suggested that single-nucleotide polymorphisms (SNPs)
      in the TNF-alpha gene have different TNF-alpha responses. This study aims to
      evaluate the effect of serum TNF-alpha levels through the interactions between
      toxic metals and essential elements and how the interactions between the toxic
      metals and TNF-alpha SNPs (-1031 T > C, -863 C > A, -857 C > T, -308 G > A, -238
      G > A) influence serum TNF-alpha levels. METHODS: Blood samples were collected
      from 455 workers who carried out annual health examinations and multielements
      determined by inductively coupled plasma mass spectrometry (ICP-MS). TNF-alpha
      levels were detected by enzyme-linked immunosorbent assay (ELISA). TNF-alpha
      promoter SNPs were analyzed by specific primer probes using real-time polymerase
      chain reaction (PCR) methods. RESULTS: Increasing blood Pb, Cd, and As levels
      were associated with elevated TNF-alpha levels. The interaction between Pb and Cu
      decreased TNF-alpha levels and so did the interaction between Cd and Se. In the
      interaction between Pb and SNPs, individuals with AA/AG (-308 G > A) and AA/AG (
      238 G > A) had higher serum TNF-alpha levels. However, lower TNF-alpha levels
      were noted in those individuals with AA/CA (-863 C > A). In the interaction
      between As and SNPs, workers with AA/AG (-238 G > A) had synergic effect with As
      and induced higher serum TNF-alpha levels. CONCLUSIONS: Blood Cu and Se were
      antagonists of toxic metals (Pb, As, and Cd) through lower serum TNF-alpha
      levels. Variant types of TNF-alpha SNPs (-308 G > A, -238 G > A) and wild type of
      -863 CC would be more susceptible to toxic metals.

PMID- 29028685
TI  - Use of Genetic Algorithm Combinational Single-nucleotide Polymorphisms Could
      Modify the Association of Blood Lead Levels and Bone Matrix Density.
AB  - BACKGROUND: Previous studies have not explored the relationship between a single
      gene and a single disease. Our study aims to investigate the association of
      multiple genotypes with blood lead levels and bone matrix density (BMD) by using
      genetic algorithms. METHODS: Our research focused on 506 employees (245 males and
      261 females) of a lead battery factory in Taiwan. We collected data on their BMD,
      blood lead level, and 6 SNPs (ACE, alpha-adducin, Bsm, Tag, Apa, and ALAD); these
      factors were analyzed using discrete binary particle swarm optimization (DBPSO)
      and logistic regression analysis. RESULTS: We found no association between blood
      lead level and bone density, which may be due to the relatively young age of this
      population (mean age = 45.1 years). However, the genotype that contained both Bsm
      type bb and ALAD type 1-1 may play an important role in protecting against lower
      bone density among these employees. CONCLUSIONS: In conclusion, this study found
      that the Bsm and ALAD genes influence bone density among lead workers. However,
      the mechanism and exact relationship between these two genes and bone density
      require further investigation.

PMID- 29028686
TI  - Interaction Between Catalase Gene Promoter Polymorphisms and Indoor Environmental
      Exposure in Childhood Allergic Rhinitis.
AB  - BACKGROUND: Allergic rhinitis (AR) is a highly prevalent chronic inflammatory
      disease affecting nearly 40% of the children in Taiwan. Genetic susceptibility
      may interact with specific environmental factors leading to allergic disease
      development. METHODS: To assess the interactions between catalase gene promoter
      polymorphisms and environmental factors on the risk of AR, we conducted a case
      control study in Taiwan. Data on AR and environmental factors were collected from
      800 children using the ISSAC questionnaire. The case group consisted of 263
      children with AR, and the control group consisted of =537 healthy children.
      Genotyping was performed for rs1001179 and rs769214 polymorphisms, and
      environmental exposure was assessed using four indicators including dwelling
      visible molds, mold odor, moisture on surfaces, and water damage. RESULTS: We
      found that the presence of visible molds, mold odor, and moisture was associated
      with AR. An apparent joint effect of the GG genotype and mold odor, compared with
      the AA and AG combined genotypes and without any exposure indicator (adjusted
      odds ratio [OR] = 1.95 [95% confidence interval (CI) = 1.20, 3.18]; interaction
      adjusted odds ratio = 2.59 [95% CI = 1.27, 5.30]), was observed. CONCLUSIONS: Our
      findings suggest that gene-environment interactions between the catalase
      polymorphism rs769214 and mold odor may play an important role in childhood AR
      development.

PMID- 29028688
TI  - Angioedema Associated With Long-Acting Injectable Paliperidone Palmitate: A Case
      Report.

PMID- 29028687
TI  - HYPERREFLECTIVE DEPOSITION IN THE BACKGROUND OF ADVANCED STARGARDT DISEASE.
AB  - PURPOSE: To describe an unusual manifestation of hyperreflective deposits in the
      subretinal space in a group of patients with clinically and genetically confirmed
      Stargardt disease. METHODS: Retrospective review of color fundus,
      autofluorescence, infrared reflectance, red-free images, and spectral domain
      optical coherence tomography in 296 clinically diagnosed and genetically
      confirmed (2 expected disease-causing mutations in ABCA4) patients with Stargardt
      disease. Full-field electroretinogram (ffERG), medical history, and genotype data
      (in silico predictions) were further analyzed from the selected cohort. RESULTS:
      Eight of 296 patients (2.7%) were found to exhibit small crystalline deposits
      that were detectable on certain imaging modalities, such as color, infrared
      reflectance and red-free images, but not autofluorescence. The deposits were most
      prevalent in the superior region of the macula, and spectral domain optical
      coherence tomography revealed their presence in the subretinal space. All
      patients presented with these findings at a notably advanced disease stage with
      abnormal ffERG and a high proportion of highly deleterious ABCA4 alleles.
      CONCLUSION: Hyperreflective subretinal deposits may be a manifestation of
      advanced ABCA4 disease, particularly in regions susceptible to disease-related
      changes, such as lipofuscin accumulation.

PMID- 29028689
TI  - Effective Switch From Clozapine to Aripiprazole in Treatment-Resistant
      Schizophrenia and Comorbid Alcohol Use Disorder.

PMID- 29028690
TI  - Adverse Event Reporting: Harnessing Residents to Improve Patient Safety.
AB  - OBJECTIVES: Reporting of adverse and near miss events are essential to identify
      system level targets to improve patient safety. Resident physicians historically
      report few events despite their role as front-line patient care providers. We
      sought to evaluate barriers to adverse event reporting in an effort to improve
      reporting. Our main outcomes were as follows: resident attitudes about event
      reporting and the frequency of event reporting before and after interventions to
      address reporting barriers. METHODS: We surveyed first year residents regarding
      barriers to adverse event reporting and used this input to construct a fishbone
      diagram listing barriers to reporting. Barriers were addressed, and resident
      event reporting was compared before and after efforts were made to reduce
      obstacles to reporting. RESULTS: First year residents (97%) recognized the
      importance of submitting event reports; however, the majority (85%) had not
      submitted an event report in the first 6 months of residency. Only 7% of
      residents specified that they had not witnessed an adverse event in 6 months,
      whereas one third had witnessed 10 or more events. The main barriers were as
      follows: lack of knowledge about how to submit events (38%) and lack of time to
      submit reports (35%). After improving resident education around event reporting
      and simplifying the reporting process, resident event reporting increased 230%
      (68 to 154 annual reports, P = 0.025). CONCLUSIONS: We were able to significantly
      increase resident event reporting by educating residents about adverse events and
      near misses and addressing the primary barriers to event reporting. Moving
      forward, we will continue annual resident education about patient safety, focus
      on improving feedback to residents who submit reports, and empower senior
      residents to act as role models to junior residents in patient safety
      initiatives.

PMID- 29028691
TI  - Job Burnout Reduces Hand Hygiene Compliance Among Nursing Staff.
AB  - OBJECTIVES: Health professional burnout has been associated with suboptimal care
      and reduced patient safety. However, the extent to which burnout influences hand
      hygiene compliance among health professionals has yet to be explored. The aim of
      the study was to examine whether job burnout reduces hand washing compliance
      among nursing staff. METHODS: A diary study was conducted. Forty registered
      nurses working in a general city hospital in Thessaloniki, Greece, completed a
      questionnaire, while they were monitored for hand hygiene compliance following
      the World Health Organization protocol for hand hygiene assessment. Burnout was
      measured using validated items from the Maslach Burnout Inventory. Data were
      collected from September to October 2015. RESULTS: Multiple regression analysis
      showed that controlling for years in practice, burnout was negatively associated
      with hand hygiene compliance (R = 0.322, F(3,36) = 5.704, P < 0.01). Nurses
      reporting higher levels of burnout were less likely to comply with hand hygiene
      opportunities (b = - 3.72, 95% confidence interval = -5.94 to -1.51).
      CONCLUSIONS: This study showed that burnout contributes to suboptimal care by
      reducing compliance to hand hygiene among nurses. Given the crucial role of hand
      hygiene compliance for the prevention of in-hospital infections, this study
      highlights the need for interventions targeting the prevention of burnout among
      nursing staff.

PMID- 29028692
TI  - The Relationship of Anxiety, Depression, and Quality of Life in Adults With Left
      Ventricular Assist Devices.
AB  - Psychological distress, including anxiety and depression, is commonly reported by
      patients with implantable left ventricular assist devices (LVADs). Still, the
      influence of anxiety and depression on global quality of life (QOL) is unknown.
      Moreover, the empirical data of LVAD patients' QOL is limited to 24 months. This
      study examined the differences in anxiety, depression, and QOL based on 3 LVAD
      implant duration groups (<=12, 13-24, and >=25 months). We also examined the
      influence of anxiety and depression on QOL. An observational cross-sectional
      study design was employed using self-administered demographics, anxiety,
      depression, and global QOL questionnaires. A total of 100 patients (mean age 52
      +/- 13.3 years) across the United States completed the study. In the 3 implant
      duration groups, we found no significant differences in anxiety and depression,
      but the global QOL scores of patients with LVADs >= 13 months were significantly
      worse than those of patients with LVADs <= 12 months. Also, the correlations
      between QOL and either anxiety or depression were significant: Pearson's r ranged
      from -0.44 to -0.65 with all p values <0.0001. Compared with anxiety, depression
      is a stronger predictor of QOL. Our data showed that when depression is increased
      by 1 unit, the average QOL decreased by 0.76 units, assuming anxiety is held
      constant. This study uncovered relationships among anxiety, depression, and QOL
      in patients with long-term LVADs. Longitudinal research is needed to confirm our
      findings and explore factors that may contribute to worse QOL, particularly,
      those patients supported with LVADs beyond 13 months.

PMID- 29028693
TI  - The Development of Pulmonary Hypertension Results in Decreased Post-Transplant
      Survival.
AB  - The effects of pulmonary hypertension (PAH) on survival after heart
      transplantation are debated, especially for patients with left ventricular assist
      devices (LVAD). The United Network of Organ Sharing database was retrospectively
      queried from January 2005 to June 2015 to identify adult patients who underwent
      heart transplantation. Four groups were defined: patients without PAH, persistent
      PAH, resolved PAH, and developed PAH between listing and transplant. A total of
      15,914 patients underwent heart transplant of which 4,662 (29%) were implanted
      with an LVAD. Of the total population, 10,872 (68%) had PAH at time of listing
      and 9,661 (61%) had PAH at time of transplant. Long-term survival was
      significantly worse for patients with an LVAD than for those without who had PAH
      at time of transplant (p = 0.010). Kaplan-Meier analysis showed a trend of worse
      long-term survival for patients with an LVAD who developed PAH by the time of
      transplant but improved survival for patients with resolved PAH while on LVAD
      therapy (p = 0.052). PAH at time of transplant results in worse long-term
      survival for patients with an LVAD. Furthermore, the development of PAH while on
      LVAD therapy may negatively impact long-term post-transplant survival, while
      resolution of PAH improves long-term survival.

PMID- 29028694
TI  - Individualized Biventricular Epicardial Augmentation Technology in a Drug-Induced
      Porcine Failing Heart Model.
AB  - For treatment of advanced heart failure, current strategies include cardiac
      transplantation or blood-contacting pump technology associated with
      complications, including stroke and bleeding. This study investigated an
      individualized biventricular epicardial augmentation technology in a drug-induced
      porcine failing heart model. A total of 11 pigs were used, for the assessment of
      hemodynamics and cardiac function under various conditions of support pressures
      and support durations (n = 4), to assess device positioning and function by in
      vivo computer tomographic imaging (n = 3) and to investigate a minimally invasive
      implantation on the beating heart (n = 4). Support pressures of 20-80 mm Hg
      gradually augmented cardiac function parameters in this animal model as indicated
      by increased left ventricular stroke volume, end-systolic pressures, and
      decreased end-diastolic pressures. Strong evidence was found regarding the
      necessity of mechanical synchronization of support end with the isovolumetric
      relaxation phase of the heart. In addition, the customized, self-expandable
      implant enabled a marker-guided minimally invasive implantation through a 4 cm
      skin incision using fluoroscopy. Correct positioning was confirmed in computer
      tomographic images. Continued long-term survival investigations will deliver
      preclinical evidence for further development of this concept.

PMID- 29028695
TI  - National Certification in Critical Care Echocardiography: Its Time Has Come.

PMID- 29028697
TI  - Machine Learning and Sepsis: On the Road to Revolution.

PMID- 29028696
TI  - Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II: A Phase II
      Randomized Trial.
AB  - OBJECTIVES: A relationship between reduced brain tissue oxygenation and poor
      outcome following severe traumatic brain injury has been reported in
      observational studies. We designed a Phase II trial to assess whether a
      neurocritical care management protocol could improve brain tissue oxygenation
      levels in patients with severe traumatic brain injury and the feasibility of a
      Phase III efficacy study. DESIGN: Randomized prospective clinical trial. SETTING:
      Ten ICUs in the United States. PATIENTS: One hundred nineteen severe traumatic
      brain injury patients. INTERVENTIONS: Patients were randomized to treatment
      protocol based on intracranial pressure plus brain tissue oxygenation monitoring
      versus intracranial pressure monitoring alone. Brain tissue oxygenation data were
      recorded in the intracranial pressure -only group in blinded fashion. Tiered
      interventions in each arm were specified and impact on intracranial pressure and
      brain tissue oxygenation measured. Monitors were removed if values were normal
      for 48 hours consecutively, or after 5 days. Outcome was measured at 6 months
      using the Glasgow Outcome Scale-Extended. MEASUREMENTS AND MAIN RESULTS: A
      management protocol based on brain tissue oxygenation and intracranial pressure
      monitoring reduced the proportion of time with brain tissue hypoxia after severe
      traumatic brain injury (0.45 in intracranial pressure-only group and 0.16 in
      intracranial pressure plus brain tissue oxygenation group; p < 0.0001).
      Intracranial pressure control was similar in both groups. Safety and feasibility
      of the tiered treatment protocol were confirmed. There were no procedure-related
      complications. Treatment of secondary injury after severe traumatic brain injury
      based on brain tissue oxygenation and intracranial pressure values was consistent
      with reduced mortality and increased proportions of patients with good recovery
      compared with intracranial pressure-only management; however, the study was not
      powered for clinical efficacy. CONCLUSIONS: Management of severe traumatic brain
      injury informed by multimodal intracranial pressure and brain tissue oxygenation
      monitoring reduced brain tissue hypoxia with a trend toward lower mortality and
      more favorable outcomes than intracranial pressure-only treatment. A Phase III
      randomized trial to assess impact on neurologic outcome of intracranial pressure
      plus brain tissue oxygenation-directed treatment of severe traumatic brain injury
      is warranted.

PMID- 29028698
TI  - Quick Sequential Organ Failure Assessment: Illness Severity Indicator, Clinical
      Decision Support Tool, or Both?

PMID- 29028699
TI  - Pediatric Acute Respiratory Distress Syndrome in Asia: None of Us Is as Smart as
      All of Us.

PMID- 29028700
TI  - Victims or Culprits, B Cells May Serve as Markers for Mortality Risk and Targeted
      Therapy in Sepsis.

PMID- 29028701
TI  - Catatonia, Delirium, and Critical Illness: A Diagnostic Statistical Manual 5
      Mystery Partially Disentangled.

PMID- 29028702
TI  - Just Because Things Are Not Different, Does Not Mean They Are the Same: Biomarker
      Patterns in Acute Respiratory Distress Syndrome.

PMID- 29028703
TI  - Sepsis in the Critically Ill-Does Gender Matter?

PMID- 29028705
TI  - Can We Boost Our Ability to Monitor Severe Brain Trauma?

PMID- 29028704
TI  - Aspirin for Sepsis Prophylaxis: An Ounce of Prevention?

PMID- 29028706
TI  - Lost in Translation, Found in Exploration: Understanding Why Interpreters Might
      Alter Communication.

PMID- 29028707
TI  - ICU-Acquired Weakness, Chronic Critical Illness, and the Persistent Inflammation
      Immunosuppression and Catabolism Syndrome.

PMID- 29028708
TI  - The authors reply.

PMID- 29028709
TI  - Ultrasound in Confirming Central Catheter Position: (Almost) Ready for Prime
      Time.

PMID- 29028710
TI  - The authors reply.

PMID- 29028711
TI  - Does Regulatory Really Intersect Reality in Glucose Measurement in the ICU? Is
      the Issue Testing Method Accuracy or Specimen Type?

PMID- 29028712
TI  - The authors reply.

PMID- 29028713
TI  - Lung Ultrasonography as the First Confirmation Method for Central Venous
      Catheterization: How Far Are We?

PMID- 29028714
TI  - The authors reply.

PMID- 29028715
TI  - The Effects of Afebrile Characteristic on Patients With Suspected Septic Shock:
      Several Facts Need to Be Noticed.

PMID- 29028716
TI  - The author replies.

PMID- 29028717
TI  - Comparing the ICU-7 to the Delirium Rating Scale.

PMID- 29028718
TI  - The author replies.

PMID- 29028719
TI  - Cardiac Function Following Traumatic Brain Injury.

PMID- 29028721
TI  - An Overlook of New-Onset Atrial Fibrillation in the Critically Ill Using
      Automated Detection: Have We Over Looked at It?

PMID- 29028720
TI  - The authors reply.

PMID- 29028722
TI  - The authors reply.

PMID- 29028723
TI  - Does Driving Pressure Matter in Pediatric Acute Respiratory Distress Syndrome?
      Strain to Find the Answer.

PMID- 29028724
TI  - The authors reply.

PMID- 29028725
TI  - Are Women Inferior Leaders in Emergency Situations? An Appeal for a More Careful
      Interpretation of Research Results.

PMID- 29028726
TI  - The authors reply.

PMID- 29028727
TI  - Smartphones to Assess Cardiac Function: Novelty Blindness or Fresh Perspectives?

PMID- 29028728
TI  - The authors reply.

PMID- 29028729
TI  - Therapeutic Hypothermia for Acute Respiratory Distress Syndrome.

PMID- 29028730
TI  - The author replies.

PMID- 29028731
TI  - When, Who, and How is Elevated Mean Airway Pressure and Central Venous Pressure
      in the First Day of Mechanical Ventilation a Sign?

PMID- 29028732
TI  - The authors reply.

PMID- 29028733
TI  - The Use of Tidal Volume Challenge Test in Critically Ill Patients: Caution
      Needed.

PMID- 29028734
TI  - The authors reply.

PMID- 29028735
TI  - Inflammatory Bowel Disease, the Hospital Anxiety and Depression Scale and
      Criterion Contamination.

PMID- 29028736
TI  - SUPERFICIAL AND DEEP CAPILLARY ISCHEMIA AS A PRESENTING SIGN OF RETINAL
      VASCULOPATHY WITH CEREBRAL LEUKOENCEPHALOPATHY AND SYSTEMIC MANIFESTATIONS.
AB  - PURPOSE: The aim of this study was to investigate the presenting sign of retinal
      vasculopathy with cerebral leukoencephalopathy and systemic manifestations, a
      rare autosomal dominant condition caused by mutations in the TREX1 gene, and to
      explore the potential efficacy of bevacizumab in preventing capillary occlusions.
      METHODS: Observational case report with the use of ultra-widefield fluorescein
      angiography, optical coherence tomography, and optical coherence tomography
      angiography. RESULTS: A 31-year-old man with a family history of retinal
      vasculopathy with cerebral leukoencephalopathy and systemic manifestations
      presented with a scotoma in his left eye. The visual acuity was 20/20 in both
      eyes, and his examination was notable for scattered cotton wool spots in the
      retina of both eyes as well as an area of paracentral acute middle maculopathy in
      the left eye. Ultra-widefield fluorescein angiography revealed peripheral
      capillary nonperfusion and vascular leakage corresponding to the cotton wool
      spots. Spectral domain optical coherence tomography and optical coherence
      tomography angiography confirmed the presence and distribution of superficial
      capillary plexus and deep capillary plexus ischemia. Neurologic examination and
      imaging were normal. A trial of monthly intravitreal bevacizumab injections to
      the left eye over 6 months resulted in diminished capillary leakage. CONCLUSION:
      Retinal vasculopathy with cerebral leukoencephalopathy and systemic
      manifestations is a rare genetic condition manifested most commonly by cerebral
      and retinal ischemia. This retinal vasculopathy leads to occlusions of small
      caliber retinal vessels in the superficial plexus and deep plexus with resulting
      cotton wool spots and paracentral acute middle maculopathy, respectively.
      Recognition of the retinal findings by ophthalmologists and neurologists may
      avoid unnecessary brain biopsies in diagnosing this rare disorder.

PMID- 29028737
TI  - Resting Pd/Pa and haemodynamic relevance of coronary stenosis as evaluated by
      fractional flow reserve.
AB  - BACKGROUND: Fractional flow reserve (FFR) currently represents the gold standard
      in the evaluation of the haemodynamic relevance of coronary stenoses. However,
      both intracoronary and intravenous adenosine may be tolerated poorly by some
      patients. Therefore, considerable interest had been focused in the last few years
      on new adenosine-free indexes to define the haemodynamic relevance of coronary
      stenoses. So far, few data have been reported on resting Pd/Pa and its
      correlation with FFR as evaluated with high-dose intracoronary adenosine
      administration, which is the aim of the current study. MATERIALS AND METHODS: FFR
      was assessed in 120 patients with 137 intermediate lesions during cardiac
      catheterization by a pressure-recording guidewire (PrimeWire). FFR was calculated
      as the ratio of the distal coronary pressure to the aortic pressure at
      hyperaemia. Intracoronary doses of adenosine were administered up to 720 MUg as
      intracoronary boli. Exclusion criteria were as follows: (a) allergy to adenosine;
      (b) baseline bradycardia (heart rate <50 bpm); (c) hypotension (blood pressure
      <90 mmHg); and (d) refusal to provide signed informed consent. RESULTS: High
      doses of intracoronary adenosine were well tolerated, with no major side effects.
      Increasing doses up to 720 MUg progressively decreased FFR values and increased
      the percentage of patients showing an FFR less than 0.80. Resting Pd/Pa showed
      good accuracy in the identification of patients with significant FFR values
      (<0.80) [area under the curve=0.9 (0.84-0.96), P<0.0001]. Using receiver
      operating characteristic curves, we identified a threshold less than 0.93 as the
      best accurate cut-off value in the prediction of a positive FFR value. A value up
      to 0.88 was associated with a 100% positive predictive value, whereas a value of
      at least 0.95 was associated with a 95% negative predictive value. CONCLUSION:
      This study showed that in intermediate lesions, resting Pd/Pa was related
      linearly to FFR. We identified 0.93 as the best cut-off value in the prediction
      of haemodynamically significant coronary stenosis as evaluated by FFR. However,
      cut-off values of 0.88 and 0.95 could provide the maximal predictive positive and
      negative values, suggesting the additional use of FFR only in patients with
      resting values within this range.

PMID- 29028738
TI  - Multiple systemic embolic events in a patient undergoing primary percutaneous
      coronary intervention: drop foot and syncope as an unusual presentation of
      subacute ST-elevation myocardial infarction.

PMID- 29028739
TI  - Association of the SYNTAX Score II with cardiac rupture in patients with ST
      segment elevation myocardial infarction undergoing a primary percutaneous
      coronary intervention.
AB  - BACKGROUND: Despite advances in reperfusion strategies, medical therapy, and
      emergent surgery, cardiac rupture (CR) is still a major lethal complication.
      Numerous parameters have been found to be associated with CR development after a
      primary percutaneous coronary intervention (pPCI). SYNTAX Score (SS) and SYNTAX
      Score II (SSII) have been studied in ST-segment elevation myocardial infarction
      (STEMI) patients, and higher scores have been associated with higher mortality.
      However, the relationship between CR and SSII is unclear. This study investigates
      the possible relationship between CR and SS, SSII in STEMI patients treated with
      pPCI. PATIENTS AND METHODS: We enrolled 1663 consecutive STEMI patients treated
      with pPCI, who were divided into two groups according to CR development and
      compared with each other. Patients were further stratified into the three groups
      according to their SSII values. RESULTS: In this study, 33 (1.98%) patients
      developed CR. Both SS and SSII of those with CR were significantly higher than
      those without (19.27+/-4.0 vs. 16.40+/-4.55; P<0.001 and 49.40+/-16.54 vs.
      30.92+/-11.80; P<0.001, respectively). It was also observed that CR increased
      gradually according to increasing SSII tertiles. SSII was found to be an
      independent predictor for CR (odds ratio=1.043, 95% confidence interval: 1.012
      1.074; P=0.006). In the long-term follow-up, all-cause mortality was
      significantly higher in patients with CR than those without (60.6 vs. 8.8%;
      P<0.001). CONCLUSION: This study shows that SSII is an independent predictor for
      CR. Furthermore, patients with CR were associated with a poor prognosis. Closer
      follow-up of patients with high SSII may be useful in the early detection and
      treatment of this fatal complication.

PMID- 29028740
TI  - Coronary vasospasm: a silent enemy in orthotopic heart transplant.

PMID- 29028741
TI  - Fundamental Epidemiology Terminology and Measures: It Really Is All in the Name.
AB  - Epidemiology is the study of how disease is distributed in populations and the
      factors that influence or determine this distribution. Clinical epidemiology
      denotes the application of epidemiologic methods to questions relevant to patient
      care and provides a highly useful set of principles and methods for the design
      and conduct of quantitative clinical research. Validly analyzing, correctly
      reporting, and successfully interpreting the findings of a clinical research
      study often require an understanding of the epidemiologic terms and measures that
      describe the patterns of association between the exposure of interest (treatment
      or intervention) and a health outcome (disease). This statistical tutorial thus
      discusses selected fundamental epidemiologic concepts and terminology that are
      applicable to clinical research. Incidence is the occurrence of a health outcome
      during a specific time period. Prevalence is the existence of a health outcome
      during a specific time period. The relative risk can be defined as the
      probability of the outcome of interest (eg, developing the disease) among exposed
      individuals compared to the probability of the same event in nonexposed
      individuals. The odds ratio is a measure of risk that compares the frequency of
      exposure to a putative causal factor in the individuals with the health outcome
      (cases) versus those individuals without the health outcome (controls). Factors
      that are associated with both the exposure and the outcome of interest need to be
      considered to avoid bias in your estimate of risk. Because it takes into
      consideration the contribution of extraneous variables (confounders), the
      adjusted odds ratio provides a more valid estimation of the association between
      the exposure and the health outcome and thus is the preferably reported measure.
      The odds ratio closely approximates the risk ratio in a cohort study or a
      randomized controlled trial when the outcome of interest does not occur
      frequently (<10%). The editors, reviewers, authors, and readers of journal
      articles should be aware of and make the key distinction between the absolute
      risk reduction and the relative risk reduction. In assessing the findings of a
      clinical study, the investigators, reviewers, and readers must determine if the
      findings are not only statistically significant, but also clinically meaningful.
      Furthermore, in deciding on the merits of a new medication or other therapeutic
      intervention, the clinician must balance the benefits versus the adverse effects
      in individual patients. The number needed to treat and the number needed to harm
      can provide this needed additional insight and perspective.

PMID- 29028742
TI  - Intraoperative Esmolol as an Adjunct for Perioperative Opioid and Postoperative
      Pain Reduction: A Systematic Review, Meta-analysis, and Meta-regression.
AB  - BACKGROUND: Esmolol is an ultrashort beta-1 receptor antagonist. Recent studies
      suggest a role for esmolol in pain response modulation. The authors performed a
      meta-analysis to determine if the intraoperative use of esmolol reduces opioid
      consumption or pain scores. METHODS: PubMed, Cochrane Database of Systematic
      Reviews, Cochrane Central Register of Controlled Trials, pubget, and Google
      Scholar were searched. Studies were included if they were randomized, placebo- or
      opioid-controlled trials written in English, and performed on patients 18 years
      of age or older. For comparison of opioid use, included studies tracked opioid
      consumption intraoperatively and/or in the postanesthesia care unit. Pain score
      comparisons were performed during the first hour after surgery. RESULTS: Seventy
      three studies were identified, 23 were included in the systematic review, and 19
      were eligible for 1 or more comparisons. In 433 patients from 7 trials,
      intraoperative esmolol decreased intraoperative opioid consumption (Standard Mean
      Difference [SMD], -1.60; 95% confidence interval [CI], -2.25 to -0.96; P <=
      .001). In 659 patients from 12 trials, intraoperative esmolol decreased
      postanesthesia care unit opioid consumption (SMD, -1.21; 95% CI, -1.66 to -0.77;
      P <= .001). In 688 patients from 11 trials, there was insufficient evidence of
      change in postoperative 1 hour pain scores (SMD, -0.60; 95% CI, -1.44 to 0.24; P
      = .163). CONCLUSIONS: This meta-analysis demonstrates that intraoperative esmolol
      use reduces both intraoperative and postoperative opioid consumption, with no
      change in postoperative pain scores.

PMID- 29028743
TI  - Standardized Care Versus Precision Medicine: Do We Really Need to Wait for Point
      of-Care Testing?

PMID- 29028744
TI  - In Response: Subcellular Energetics and Metabolism: A Cross-Species Framework.

PMID- 29028745
TI  - In Response: Standardized Care Versus Precision Medicine; Do We Really Need to
      Wait for Point-of-Care Testing?

PMID- 29028746
TI  - Subcellular Energetics and Metabolism: A Cross-Species Framework.

PMID- 29028748
TI  - Problematic use of prescribed opioids for chronic noncancer pain-no scarcity of
      data outside the United States.

PMID- 29028747
TI  - Nervous system delivery of antilysophosphatidic acid antibody by nasal
      application attenuates mechanical allodynia after traumatic brain injury in rats.
AB  - Lysophosphatidic acid (LPA) is a bioactive lipid that impacts neurological
      outcomes after neurotrauma by inhibiting neuroregeneration, promoting
      inflammation, and contributing to behavioral deficits. Blocking LPA signaling
      with a novel anti-LPA monoclonal antibody (mAb) is neuroprotective after
      traumatic brain injury (TBI) if given to injured animals whose blood-brain
      barrier (BBB) has been compromised. It is hypothesized that the anti-LPA mAb
      could improve chronic pain initiated by TBI. However, poor brain penetration
      after systemic application of the antibody makes access to the central nervous
      system (CNS) problematic in situations where the BBB is intact. Our experiments
      investigated whether intranasal delivery of the anti-LPA mAb could bypass the
      BBB, allowing for direct entry of the antibody to certain areas of the CNS. When
      the humanized anti-LPA mAb, LT3114, was intranasally applied to injured rats
      within 30 minutes after mild TBI using the central lateral percussion model,
      enzyme-linked immunospecific assay and immunohistochemistry demonstrated antibody
      uptake to several areas in the CNS, including the area of cortical injury, the
      corpus callosum, cerebellum, and the subventricular region. Compared with control
      rats that received LT3114 but no TBI, TBI rats demonstrated significantly higher
      concentrations of intranasally administered LT3114 antibody in some tissues. In
      behavioral studies, a significant attenuation of mechanical allodynia after TBI
      was observed in the anti-LPA treatment group (P = 0.0079), when compared with
      vehicle controls within 14 days after TBI. These results suggest that intranasal
      application of the anti-LPA antibody directly accesses CNS sites involved in TBI
      related pain and that this access attenuates pain sequelae to the neurotrauma.

PMID- 29028749
TI  - Reply.

PMID- 29028750
TI  - Injuries to the Female Athlete in 2017: Part I: General Considerations,
      Concussions, Stress Fractures, and the Female Athlete Triad.

PMID- 29028751
TI  - Injuries to the Female Athlete in 2017: Part II: Upper and Lower-Extremity
      Injuries.

PMID- 29028752
TI  - Point-Counterpoint: Cost-Effectiveness Analysis in Medical Care and the Issue of
      Economic Model Transparency.

PMID- 29028753
TI  - Can Economic Model Transparency Improve Provider Interpretation of Cost
      effectiveness Analysis? Evaluating Tradeoffs Presented by the Second Panel on
      Cost-effectiveness in Health and Medicine.
AB  - The Second Panel on Cost-Effectiveness in Health and Medicine convened on
      December 7, 2016 at the National Academy of Medicine to disseminate their
      recommendations for conduct, methodological practices, and reporting of cost
      effectiveness analyses (CEAs). Following its summary, panel proceedings included
      lengthy discussions including the field's struggle to disseminate findings
      efficiently through peer-reviewed literature to target audiences. With editors of
      several medical and outcomes research journals in attendance, there was consensus
      that findings of cost-effectiveness analyses do not effectively reach other
      researchers or health care providers. The audience members suggested several
      solutions including providing additional training to clinicians in cost
      effectiveness research and requiring that cost-effectiveness models are made
      publicly available. However, there remains the questions of whether making
      economic modelers' work open-access through journals is fair under the defense
      that these models remain one's own intellectual property, or whether journals can
      properly manage the peer-review process specifically for cost-effectiveness
      analyses. In this article, we elaborate on these issues and provide some
      suggested solutions that may increase the dissemination and application of cost
      effectiveness literature to reach its intended audiences and ultimately benefit
      the patient. Ultimately, it is our combined view as economic modelers and
      clinicians that cost-effectiveness results need to reach the clinician to improve
      the efficiency of medical practice, but that open-access models do not improve
      clinician access or interpretation of the economics of medicine.

PMID- 29028754
TI  - Can Economic Model Transparency Improve Provider Interpretation of Cost
      Effectiveness Analysis? A Response.
AB  - To enhance the credibility and the value of health economic analyses, we argue
      that the computer model source code underlying these analyses should be made
      publicly available. Only with open publication is it possible for others to
      assess whether alternative assumptions, beyond those examined by the model
      authors, alter the model's findings. Because reproducibility is critical for
      scientific acceptance and because computation increasingly permeates scientific
      inquiry, other fields have moved toward open publication of computer models, and
      health economics should avoid falling behind. Making source code available shines
      a light on these otherwise black boxes and facilitates their complete evaluation
      and understandability. The preceding commentary makes 2 arguments against open
      publication. It claims first that open publication would undermine intellectual
      property rights and discourage work in this field. We respond that the impact on
      intellectual property would be minimal, and that open publication could even
      increase model value. The second argument against open publication is the
      possibility of model misuse. If anything, however, open publication would reduce
      this risk by making the model implementation completely transparent. We argue
      finally that open publication of models would have ancillary benefits by making
      the research more amenable for adaptation and innovation. Moving toward open
      publication will present challenges, but we believe that the benefits of
      increased scientific credibility and utility, particularly for health policy and
      clinical practice decisions, will certainly outweigh the harms.

PMID- 29028755
TI  - Finding Resolution for the Responsible Transparency of Economic Models in Health
      and Medicine.
AB  - The Second Panel on Cost-Effectiveness in Health and Medicine recommendations for
      conduct, methodological practices, and reporting of cost-effectiveness analyses
      has a number of questions unanswered with respect to the implementation of
      transparent, open source code interface for economic models. The possibility of
      making economic model source code could be positive and progressive for the
      field; however, several unintended consequences of this system should be first
      considered before complete implementation of this model. First, there is the
      concern regarding intellectual property rights that modelers have to their
      analyses. Second, the open source code could make analyses more accessible to
      inexperienced modelers, leading to inaccurate or misinterpreted results. We
      propose several resolutions to these concerns. The field should establish a
      licensing system of open source code such that the model originators maintain
      control of the code use and grant permissions to other investigators who wish to
      use it. The field should also be more forthcoming towards the teaching of cost
      effectiveness analysis in medical and health services education so that providers
      and other professionals are familiar with economic modeling and able to conduct
      analyses with open source code. These types of unintended consequences need to be
      fully considered before the field's preparedness to move forward into an era of
      model transparency with open source code.

PMID- 29028756
TI  - Financial Performance of Hospitals in the Mississippi Delta Region Under the
      Hospital Readmissions Reduction Program and Hospital Value-based Purchasing
      Program.
AB  - BACKGROUND: Previous studies showed that the Hospital Readmissions Reduction
      Program (HRRP) and the Hospital Value-based Purchasing Program (HVBP)
      disproportionately penalized hospitals caring for the poor. The Mississippi Delta
      Region (Delta Region) is among the most socioeconomically disadvantaged areas in
      the United States. The financial performance of hospitals in the Delta Region
      under both HRRP and HVBP remains unclear. OBJECTIVE: To compare the differences
      in financial performance under both HRRP and HVBP between hospitals in the Delta
      Region (Delta hospitals) and others in the nation (non-Delta hospitals). RESEARCH
      DESIGN: We used a 7-year panel dataset and applied difference-in-difference
      models to examine operating and total margin between Delta and non-Delta
      hospitals in 3 time periods: preperiod (2008-2010); postperiod 1 (2011-2012); and
      postperiod 2 (2013-2014). RESULTS: The Delta hospitals had a 0.89% and 4.24%
      reduction in operating margin in postperiods 1 and 2, respectively, whereas the
      non-Delta hospitals had 1.13% and 1% increases in operating margin in postperiods
      1 and 2, respectively. The disparity in total margins also widened as Delta
      hospitals had a 1.98% increase in postperiod 1, but a 0.30% reduction in
      postperiod 2, whereas non-Delta hospitals had 1.27% and 2.28% increases in
      postperiods 1 and 2, respectively. CONCLUSIONS: The gap in financial performance
      between Delta and non-Delta hospitals widened following the implementation of
      HRRP and HVBP. Policy makers should modify these 2 programs to ensure that
      resources are not moved from the communities that need them most.

PMID- 29028757
TI  - Patient Experience-based Value Sets: Are They Stable?
AB  - BACKGROUND: Although societal preference weights are desirable to inform resource
      allocation decision-making, patient experienced health state-based value sets can
      be useful for clinical decision-making, but context may matter. OBJECTIVE: To
      estimate EQ-5D value sets using visual analog scale (VAS) ratings for patients
      undergoing knee replacement surgery and compare the estimates before and after
      surgery. METHODS: We used the Patient Reported Outcome Measures data collected by
      the UK National Health Service on patients undergoing knee replacement from 2009
      to 2012. Generalized least squares regression models were used to derive value
      sets based on the EQ-5D-3 level using a development sample before and after
      surgery, and model performance was examined using a validation sample. RESULTS: A
      total of 90,450 preoperative and postoperative valuations were included. For
      preoperative valuations, the largest decrement in VAS values was associated with
      the dimension of anxiety/depression, followed by self-care, mobility, usual
      activities, and pain/discomfort. However, pain/discomfort had a greater impact on
      VAS value decrement in postoperative valuations. Compared with preoperative
      health problems, postsurgical health problems were associated with larger value
      decrements, with significant differences in several levels and dimensions,
      including level 2 of mobility, level 2/3 of usual activities, level 3 of
      pain/discomfort, and level 3 of anxiety/depression. Similar results were observed
      across subgroups stratified by age and sex. CONCLUSIONS: Findings suggest patient
      experience-based value sets are not stable (ie, context such as timing matters).
      However, the knowledge that lower values are assigned to health states
      postsurgery compared with presurgery may be useful for the patient-doctor
      decision-making process.

PMID- 29028758
TI  - MR Neurography of Lumbosacral Plexus in Failed Back Surgery Syndrome.
AB  - STUDY DESIGN: Retrospective clinical case series. OBJECTIVE: To study the role of
      MRN of lumbosacral plexus in management of patients with FBSS. SUMMARY OF
      BACKGROUND DATA: Failed back surgery syndrome (FBSS) is one of the major problems
      in health care, affecting up to 40% of patients following spine surgery. To date,
      no imaging modality has been used to effectively classify nerve compression,
      since nerve injuries are challenging to detect on conventional lumbar spine MRI.
      To our knowledge, no previous studies have addressed the use of MR Neurography
      (MRN) in FBSS or compared it to lumbar spine MRI. METHODS: From 203 consecutive
      3T MRN studies of lumbosacral plexus in one year, 12% (25/203) presented as FBSS.
      Demographic data, number of previous lumbar MRIs and their findings, MRN
      findings, interval between MRI and MRN, pre-and post-MRN diagnosis, pain levels,
      and treatments were recorded. Changes in diagnosis, treatment and outcomes
      following MRN were determined. RESULTS: The final sample of 25 patients had a
      mean age 62 +/- 15 and male to female ratio 1:1.08. 88% (22/25) had previous
      lumbar MRI, of which 27% had 3 or more. Most common imaging findings were
      neuroforaminal stenosis 22.6% (7/31) on MRI and neuropathy 22.9% (19/83) on MRN.
      Mean interval between MRI and MRN was 13.9 +/- 28.3 months. Lumbar MRIs were
      inconclusive in 36% (8/22). MRN detected 63% (52/83) more findings and changed
      the diagnosis and treatment in 12% and 48% of FBSS cases, respectively. Favorable
      outcomes were recorded in 40-67% of patients following MRN guided treatments.
      CONCLUSION: FBSS is a complex problem and MRN of lumbosacral plexus impacts its
      management by better directing source of symptoms. LEVEL OF EVIDENCE: 4.

PMID- 29028759
TI  - Which Domains of the ODI Best Predict Change in Physical Function in Patients
      After Surgery for Degenerative Lumbar Spondylolisthesis?
AB  - STUDY DESIGN: A retrospective review. OBJECTIVE: The purpose of this study is to
      determine the differential improvement of the various individual items of the
      Oswestry Disability Index (ODI) and to determine their relationship to other
      measures of Health Related Quality of Life (HRQOL). SUMMARY OF BACKGROUND DATA:
      The ODI is an easily scored, common, 10-item questionnaire about symptoms
      relevant to lumbar spine pathology. It is not clear if all of the items can be
      reliably applied to spine surgery. The purpose of this study is to determine the
      differential improvement of the various individual items of the ODI and to
      determine their relationship to other measures of HRQOL. METHODS: Analysis of a
      prospective registry of patients treated at an academic medical center was
      undertaken. At baseline, standardized outcome measures including ODI and SF12 PCS
      were collected on all patients undergoing elective fusion surgery for
      degenerative spondylolisthesis. Multiple linear regressions were performed using
      change in SF12 PCS as the dependent variable and change in ODI components as the
      independent variables. RESULTS: Baseline and 1-year follow-up data were collected
      on 196 patients (mean age 60.4 years). There were statistically significant
      differences in improvement among ODI items. Surprisingly, the most improvement
      after surgery was noted in the standing, sex life, and social life domains. The
      least improvement was noted in the personal care, sleeping, and sitting domains.
      Linear regression for change in ODI components versus change in SF-12 PCS
      revealed a significant correlation (R = 0.353, P <= 0.001). The only retained
      domains in the final model were change in lifting, standing, and traveling as
      predictors for DeltaPCS. CONCLUSION: All domains of the ODI do not improve
      equally after surgery for degenerative spondylolisthesis. Some of the domains
      that improve most (e.g., sex life) have no discernible relationship to the known
      pathophysiology of degenerative spondylolisthesis. Based upon these results, we
      conclude that the item bank and composite scoring of the ODI are inappropriate
      for evaluating quality of life in studies of surgically treated degenerative
      spondylolisthesis patients. LEVEL OF EVIDENCE: 3.

PMID- 29028760
TI  - The Impact of Metastatic Spinal Tumor Location on 30-Day Perioperative Mortality
      and Morbidity After Surgical Decompression.
AB  - STUDY DESIGN: A retrospective cohort study from 2011 to 2014 was performed using
      the American College of Surgeons National Surgical Quality Improvement Program
      database. OBJECTIVE: The purpose of this study was to assess the impact of tumor
      location in the cervical, thoracic, or lumbosacral spine on 30-day perioperative
      mortality and morbidity after surgical decompression of metastatic extradural
      spinal tumors. SUMMARY OF BACKGROUND DATA: Operative treatment of metastatic
      spinal tumors involves extensive procedures that are associated with significant
      complication rates and healthcare costs. Past studies have examined various risk
      factors for poor clinical outcomes after surgical decompression procedures for
      spinal tumors, but few studies have specifically investigated the impact of tumor
      location on perioperative mortality and morbidity. METHODS: We identified 2238
      patients in the American College of Surgeons National Surgical Quality
      Improvement Program database who underwent laminectomy for excision of metastatic
      extradural tumors in the cervical, thoracic, or lumbosacral spine. Baseline
      patient characteristics were collected from the database. Univariate and
      multivariate regression analyses were performed to examine the association
      between spinal tumor location and 30-day perioperative mortality and morbidity.
      RESULTS: On univariate analysis, cervical spinal tumors were associated with the
      highest rate of pulmonary complications. Multivariate regression analysis
      demonstrated that cervical spinal tumors had the highest odds of multiple
      perioperative complications. However, thoracic spinal tumors were associated with
      the highest risk of intra- or postoperative blood transfusion. In contrast,
      patients with metastatic tumors in the lumbosacral spine had lower odds of
      perioperative mortality, pulmonary complications, and sepsis. CONCLUSION: Tumor
      location is an independent risk factor for perioperative mortality and morbidity
      after surgical decompression of metastatic spinal tumors. The addition of tumor
      location to existing prognostic scoring systems may help to improve their
      predictive accuracy. LEVEL OF EVIDENCE: 3.

PMID- 29028761
TI  - The Value of 24/7 In-House ICU Staffing 24/7 Intensivist in the ICU.

PMID- 29028762
TI  - Intermittent Versus Continuous and Intermittent Medications for Pain and Sedation
      After Pediatric Cardiothoracic Surgery; A Randomized Controlled Trial.
AB  - OBJECTIVES: Compare continuous infusions of morphine and midazolam in addition to
      intermittent doses with an intermittent only strategy for pain and sedation after
      pediatric cardiac surgery. DESIGN: Randomized controlled trial. SETTING: Advocate
      Children's Hospital, Oak Lawn, IL. PATIENTS: Sixty patients 3 months to 4 years
      old with early extubation after pediatric cardiac surgery. INTERVENTIONS:
      Patients received a continuous infusion of morphine and midazolam or placebo for
      24 hours. Both groups received intermittent morphine and midazolam doses as
      needed. MEASUREMENTS AND MAIN RESULTS: Gender, age, bypass time, and surgical
      complexity were not different between groups. Scheduled ketorolac and
      acetaminophen were used in both groups and were not associated with adverse
      events. The mean, median, and maximum Faces, Legs, Activity, Cry, And
      Consolability score were not different between groups. There was no significant
      difference in number of intermittent doses received between groups. The total
      morphine dose was higher in the continuous/intermittent group (0.90 vs 0.23
      mg/kg; p < 0.01). The total midazolam dose was also higher in the
      continuous/intermittent group (0.90 vs 0.18 mg/kg; p < 0.01). The hospital length
      of stay was longer in the continuous/intermittent group (8.4 vs 4.9 d; p = 0.04).
      CONCLUSIONS: Pain was not better controlled with the addition of continuous
      infusions of morphine and midazolam when compared with intermittent dosing only.
      Use of continuous infusions resulted in a significantly higher total dosage of
      these medications and a longer length of stay.

PMID- 29028763
TI  - Effects of Hyperoxia During Resuscitation From Hemorrhagic Shock in Swine With
      Preexisting Coronary Artery Disease.
AB  - OBJECTIVES: Investigation of the effects of hyperoxia during resuscitation from
      hemorrhagic shock in swine with preexisting coronary artery disease. DESIGN:
      Prospective, controlled, randomized trial. SETTING: University animal research
      laboratory. SUBJECTS: Nineteen hypercholesterolemic pigs with preexisting
      coronary artery disease. INTERVENTIONS: Anesthetized, mechanically ventilated,
      and surgically instrumented pigs underwent 3 hours of hemorrhagic shock (removal
      of 30% of the calculated blood volume and subsequent titration of mean arterial
      blood pressure ~40 mm Hg). Postshock resuscitation (48 hr) comprised
      retransfusion of shed blood, crystalloids (balanced electrolyte solution), and
      norepinephrine support. Pigs were randomly assigned to "control" (FIO2 0.3,
      adjusted for arterial oxygen saturation >= 90%) and "hyperoxia" (FIO2 1.0 for 24
      hr) groups. MEASUREMENTS AND MAIN RESULTS: Before, at the end of shock and every
      12 hours of resuscitation, datasets comprising hemodynamics, calorimetry, blood
      gases, cytokines, and cardiac and renal function were recorded. Postmortem,
      organs were sampled for immunohistochemistry, western blotting, and mitochondrial
      high-resolution respirometry. Survival rates were 50% and 89% in the control and
      hyperoxia groups, respectively (p = 0.077). Apart from higher relaxation constant
      tau at 24 hours, hyperoxia did not affect cardiac function. However, troponin
      values were lower (2.2 [0.9-6.2] vs 6.9 [4.8-9.8] ng/mL; p < 0.05) at the end of
      the experiment. Furthermore, hyperoxia decreased cardiac 3-nitrotyrosine
      formation and increased inducible nitric oxide synthase expression. Plasma
      creatinine values were lower in the hyperoxia group during resuscitation
      coinciding with significantly improved renal mitochondrial respiratory capacity
      and lower 3-nitrotyrosine formation. CONCLUSIONS: Hyperoxia during resuscitation
      from hemorrhagic shock in swine with preexisting coronary artery disease reduced
      renal dysfunction and cardiac injury, potentially resulting in improved survival,
      most likely due to increased mitochondrial respiratory capacity and decreased
      oxidative and nitrosative stress. Compared with our previous study, the present
      results suggest a higher benefit of hyperoxia in comorbid swine due to an
      increased susceptibility to hemorrhagic shock.

PMID- 29028764
TI  - The Prognostic Value of MRI in Moderate and Severe Traumatic Brain Injury: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: Traumatic brain injury is a major cause of death and disability, yet
      many predictors of outcome are not precise enough to guide initial clinical
      decision-making. Although increasingly used in the early phase following
      traumatic brain injury, the prognostic utility of MRI remains uncertain. We thus
      undertook a systematic review and meta-analysis of studies evaluating the
      predictive value of acute MRI lesion patterns for discriminating clinical outcome
      in traumatic brain injury. DATA SOURCES: MEDLINE, EMBASE, BIOSIS, and CENTRAL
      from inception to November 2015. STUDY SELECTION: Studies of adults who had MRI
      in the acute phase following moderate or severe traumatic brain injury. Our
      primary outcomes were all-cause mortality and the Glasgow Outcome Scale. DATA
      EXTRACTION: Two authors independently performed study selection and data
      extraction. We calculated pooled effect estimates with a random effects model,
      evaluated the risk of bias using a modified version of Quality in Prognostic
      Studies and determined the strength of evidence with the Grading of
      Recommendations, Assessment, Development, and Evaluation. DATA SYNTHESIS: We
      included 58 eligible studies, of which 27 (n = 1,652) contributed data to meta
      analysis. Brainstem lesions were associated with all-cause mortality (risk ratio,
      1.78; 95% CI, 1.01-3.15; I = 43%) and unfavorable Glasgow Outcome Scale (risk
      ratio, 2.49; 95% CI, 1.72-3.58; I = 81%) at greater than or equal to 6 months.
      Diffuse axonal injury patterns were associated with an increased risk of
      unfavorable Glasgow Outcome Scale (risk ratio, 2.46; 95% CI, 1.06-5.69; I = 74%).
      MRI scores based on lesion depth demonstrated increasing risk of unfavorable
      neurologic outcome as more caudal structures were affected. Most studies were at
      high risk of methodological bias. CONCLUSIONS: MRI following traumatic brain
      injury yields important prognostic information, with several lesion patterns
      significantly associated with long-term survival and neurologic outcome. Given
      the high risk of bias in the current body of literature, large well-controlled
      studies are necessary to better quantify the prognostic role of early MRI in
      moderate and severe traumatic brain injury.

PMID- 29028765
TI  - Preventing clinical progression and need for treatment in patients on active
      surveillance for prostate cancer.
AB  - PURPOSE OF REVIEW: Active surveillance is an established treatment option for men
      with localized, low-risk prostate cancer (CaP). It entails the postponement of
      immediate therapy with the option of delayed intervention upon disease
      progression. The rate of clinical progression and need for treatment on active
      surveillance is approximately 50% over 15 years. The present review summarizes
      recent data on current methods, attempting to prevent clinical progression.
      RECENT FINDINGS: Patient selection for active surveillance is the first mandatory
      step required to lower progression. Adherence to active surveillance protocols is
      critical in making sure patients are monitored well and treated early when
      progression occurs. Before active surveillance allocation and during active
      surveillance follow-up, methods involving multiparametric MRI, prostate specific
      antigen derivatives, biopsy factors, urinary, tissue and genetic markers can be
      used to prevent clinical progression and/or identify those at risk for
      progression. Medications such as 5alpha-reductase inhibitors and others might
      inhibit disease progression in patients on active surveillance. SUMMARY: Active
      surveillance is required because of overdiagnosis, along with our inability to
      accurately predict individual CaP behavior. Several methods can potentially
      reduce the risk of CaP progression in patients with active surveillance. However,
      a measure of uncertainty and fear of progression will always accompany patients
      with active surveillance and the physicians treating them.

PMID- 29028766
TI  - Immunotherapy for metastatic urothelial carcinoma: status quo and the future.
AB  - PURPOSE OF REVIEW: The treatment paradigm of urothelial carcinoma has been
      revolutionized by the advent of multiple anti-programmed-cell death-1/ligand-1
      (PD-1/PD-L1) antibodies. Significant improvements have been obtained in the
      locally advanced or metastatic stage, which was lacking of therapeutic standards.
      This review reports key findings from completed and ongoing clinical trials that
      highlight the potential of PD-1/PD-L1 blockade in this disease. RECENT FINDINGS:
      Anti-PD-1/PD-L1 monoclonal antibodies have shown efficacy and safety in patients
      with urothelial carcinoma, regardless of their prognostic features. Efficacy was
      similar across different compounds, with objective responses that approximate
      20%, with some differences favoring PD-L1-expressing patients. Typically,
      responding patients have good chances of achieving durable response, but
      biomarkers predictive of therapeutic effect are lacking. To date, evidences from
      randomized studies are limited to the second-line, postplatinum therapy. SUMMARY:
      Despite the activity of PD-1/PD-L1 inhibitors is well established in metastatic
      urothelial carcinoma, multiple gray zones still exist regarding their optimal use
      in clinical practice. These uncertainties are related to patient and treatment
      related criteria, to the optimal duration of treatment, including combination or
      sequence with standard chemotherapy. Special issues are represented by
      pseudoprogression or hyperprogression. Generally, enhanced predictive tools are
      needed and a myriad of further investigations are underway.

PMID- 29028767
TI  - Prostate-specific membrane antigen-guided salvage lymph node dissection in
      recurrent prostate cancer: a novel technology to detect lymph node metastases.
AB  - PURPOSE OF REVIEW: With Gallium (Ga)-prostate-specific membrane antigen (PSMA)
      PET/computed tomography (CT) as emerging imaging technique offering superior
      detection rates in biochemical recurrent prostate cancer, salvage lymph node
      dissection has gained increasing interest in localized oligometastatic prostate
      cancer. Currently, PSMA-targeting small molecules cannot only be linked to
      positron-emitting isotopes for imaging but also be labelled with gamma-radiation
      emitting isotopes. These modified PSMA agents are evaluated for intraoperative
      guidance for resection of metastatic lymph nodes. This review aims to review
      current knowledge on the novel technique of PSMA-radioguided surgery. RECENT
      FINDINGS: Recently radiolabeling of PSMA ligands with Indium and Technetium as
      gamma emitter has been established. After preoperative intravenous injection of
      these novel PSMA agents single photon emission computed tomography/CT imaging can
      be performed using the gamma-emitting properties. Although its diagnostic
      performance seems to be inferior to Ga-PSMA PET/CT, intraoperative guidance by
      the use of a gamma probe was reported to facilitate detection and resection of
      tumour-infiltrated soft tissue. First follow-up data suggests favourable outcomes
      concerning prostate-specific antigen progression and treatment-free survival in a
      subset of patients. SUMMARY: Although current knowledge is still limited and
      published data is sparse salvage surgery in recurrent prostate cancer facilitated
      by gamma-emitting PSMA agents seems feasible. However, careful identification of
      ideal candidates for those procedures is mandatory.

PMID- 29028768
TI  - Hydrogen Gas Treatment Improves the Neurological Outcome After Traumatic Brain
      Injury Via Increasing miR-21 Expression.
AB  - Hydrogen gas (H2) exerts a beneficial effect against traumatic brain injury
      (TBI). microRNA-21 (miR-21) is one of the most highly expressed members of small
      non-coding microRNA family in mammalian cells. miR-21 can improve the
      neurological outcome after TBI. In the present study, we investigated whether H2
      treatment could improve the neurological outcome after TBI via increasing miR-21
      expression. TBI was induced by controlled cortical impact in rats. H2 treatment
      was given by exposure to 2% H2 from 30 min to 5 h after TBI operation. Here, we
      found that H2 treatment significantly increased the expression of miR-21 in brain
      from 6 h to 3 d after TBI. The level of miR-21 expression in brain was
      significantly decreased after intracerebroventricular infusion of miR-21
      antagomir in TBI-challenged rats with or without H2 treatment. Moreover, we found
      that H2 treatment conferred a better neurological outcome after TBI by improving
      neurological dysfunction, alleviating brain edema as well as decreasing lesion
      volume and blood-brain barrier permeability, which were significantly prevented
      by miR-21 antagomir. Furthermore, intracerebroventricular infusion of miR-21
      agomir increased the level of miR-21 expression and decreased the lesion volume
      after TBI. In addition, H2 treatment decreased the levels of oxidative products
      (malondialdehyde and 8-iso-prostaglandin F2alpha) and increased the activities of
      endogenous antioxidant enzymes (superoxide dismutase and catalase) in brain after
      TBI, which were prevented by miR-21 antagomir. Taken together, these data
      indicate that H2 treatment improves the neurological outcome after TBI via
      increasing miR-21 expression.

PMID- 29028769
TI  - Activation of the Nuclear Receptor Fxr Improves Intestinal Cell Tolerance to
      Ischemia-Reperfusion Injury.
AB  - The farnesoid X receptor (FXR) plays an important role in bile acid metabolism,
      intestinal homeostasis, and intestinal ischemia-reperfusion (I/R) injury. We
      aimed to clarify the potential effects of FXR on intestinal epithelial cell
      tolerance to intestinal I/R injury and reveal the underlying mechanisms. An
      intestinal I/R injury model was established by the occlusion of the superior
      mesenteric artery for ischemia for 1 h, followed by reperfusion for 4 h in
      C57BL/6 (wild type [WT]) and FXR mice. The small intestine injury was assessed by
      histological analysis. Diamine oxidase and TNF-alpha levels in the serum were
      measured. Expressions of Bcl-2, Bax, caspase-3, and cystathionine-gamma-lyase
      (CSE) were determined by immunohostochemical staining. Oxygen-glucose
      deprivation/reperfusion (OGD/R) was used to make injury in cultured Caco-2 cells
      pretreated with FXR agonist (INT-747) or DL-propargylglycine (PAG) for 24 h. Cell
      viability and the expressions of NF-kappaB, TNF-alpha, and IL-6 were assessed.
      Compared with WT I/R mice, FXR knockout mice exacerbated intestinal I/R injury,
      intestinal epithelial apoptosis, and inflammatory response. The I/R injury in WT
      mice was alleviated with INT-747 pretreatment. CSE expression increased after
      intestinal I/R injury in WT but not in FXR mice. INT-747 enhanced Caco-2 cell
      viability and inhibited inflammatory response by blocking the NF-kappaB pathway
      after OGD/R injury, which was diminished by a CSE-specific inhibitor (PAG). Thus,
      we demonstrated that FXR activation enhances intestinal epithelial cell tolerance
      to I/R by suppressing the inflammatory response and NF-kappaB pathway via CSE
      mediation.

PMID- 29028770
TI  - Expression and Clinical Correlations of Costimulatory Molecules on Peripheral T
      Lymphocyte Subsets of Early-Stage Severe Sepsis: A Prospective Observational
      Study.
AB  - OBJECTIVE: The aim of the study was to investigate the expression and clinical
      correlations of costimulatory molecules on peripheral T-cell subsets of severe
      sepsis (SS) patients. METHODS: Blood samples of patients with community-acquired
      pneumonia-associated SS and healthy controls (HCs) were analyzed. SS patients
      were followed up for 28 days. Costimulatory molecule expression on T-cell subsets
      was determined by flow cytometry analysis. The clinical correlations of these
      parameters were examined. RESULTS: A total of 92 SS patients and 29 HCs were
      recruited. Higher frequency of CD28, CD27, OX40 on CD4+ T cells, OX40 on CD4+CD27
      CD28- T cells and lower frequency of CD4+CD27-CD28- T cells in the SS group
      compared with the HC group and in the nonsurvived SS group compared with the
      survived SS subgroup were observed. The SS group and the nonsurvived SS subgroup
      exhibited lower frequency of 4-1BB on either CD8+ or CD4+ T cells. The frequency
      of regulatory T cells (Tregs), OX40+ Tregs and 4-1BB+ conventional T cells
      (Tconvs) were higher in the SS group. The frequency of CD4+CD27+ T cells,
      CD4+CD28+ T cells, and OX40+ on CD4+CD27-CD28- T cells were positively correlated
      with the sequential organ failure assessment (SOFA) score. The frequency of
      CD4+CD27+ T cells and OX40+ on CD4+CD27-CD28- T cells independently predicted 28
      day mortality. CONCLUSIONS: Early-stage SS patients exhibited an activated T-cell
      phenotype. Imbalanced OX40 and 4-1BB expression presented on Tregs and Tconvs may
      contribute to a functional imbalance of Tregs/Tconvs. The frequency of CD4+CD27+
      T cells and OX40+ on CD4+CD27-CD28- T cells predicted 28-day mortality of SS.

PMID- 29028771
TI  - Mechanisms of Thrombocytopenia During Septic Shock: A Multiplex Cluster Analysis
      of Endogenous Sepsis Mediators.
AB  - BACKGROUND: Thrombocytopenia is a common feature of sepsis and may involve
      various mechanisms often related to the inflammatory response. This study aimed
      at evaluating factors associated with thrombocytopenia during human septic shock.
      In particular, we used a multiplex analysis to assess the role of endogenous
      sepsis mediators. METHODS: Prospective, observational study. Thrombocytopenia was
      defined as an absolute platelet count <100 G/L or a 50% relative decrease in
      platelet count during the first week of septic shock. Plasma concentrations of 27
      endogenous mediators involved in sepsis and platelet pathophysiology were
      assessed at day-1 using a multi-analyte Milliplex human cytokine kit. Patients
      with underlying diseases at risk of thrombocytopenia (hematological malignancies,
      chemotherapy, cirrhosis, and chronic heart failure) were excluded. RESULTS:
      Thrombocytopenia occurred in 33 (55%) of 60 patients assessed. Patients with
      thrombocytopenia were more prone to present with extrapulmonary infections and
      bacteremia. Disseminated intravascular coagulation was frequent (81%) in these
      patients. Unbiased hierarchical clustering identified five different clusters of
      sepsis mediators, including one with markers of platelet activation (e.g.,
      thrombospondin-1) positively associated with platelet count, one with markers of
      inflammation (e.g., tumor necrosis factor alpha and heat shock protein 70), and
      endothelial dysfunction (e.g., intercellular adhesion molecule-1 and vascular
      cell adhesion molecule-1) negatively associated with platelet count, and another
      involving growth factors of thrombopoiesis (e.g., thrombopoietin), also
      negatively associated with platelet count. Surrogates of hemodilution (e.g.,
      hypoprotidemia and higher fluid balance) were also associated with
      thrombocytopenia. CONCLUSION: Multiple mechanisms seemed involved in
      thrombocytopenia during septic shock, including endothelial
      dysfunction/coagulopathy, hemodilution, and altered thrombopoiesis.

PMID- 29028772
TI  - Heme Oxygenase-1 Protects the Liver from Septic Injury by Modulating TLR4
      Mediated Mitochondrial Quality Control in Mice.
AB  - Mitochondrial dysfunction is involved in the pathogenesis of sepsis-induced
      multiple organ dysfunction syndrome (MODS). Mitochondrial quality control (QC) is
      characterized by self-recovering mitochondrial damage through mitochondrial
      biogenesis, mitophagy, and fission/fusion. Heme oxygenase (HO)-1 acts as a
      signaling molecule to modulate inflammation. The present study elucidated the
      cytoprotective mechanisms of HO-1 in sepsis, particularly focusing on toll-like
      receptor (TLR)4-mediated mitochondrial QC. Mice were subjected to sepsis by cecal
      ligation and puncture (CLP). The mice were injected intraperitoneally with hemin
      (10 mg/kg) at 12 h before CLP or zinc protoporphyrin IX (ZnPP; 30 mg/kg) at 2 h
      before CLP. The serum and tissues were collected 6 h after CLP. Mortality, MODS,
      and proinflammatory cytokines increased in septic mice. These increases were
      augmented by ZnPP but attenuated by hemin. Hemin decreased mitochondrial lipid
      peroxidation and mitochondrial dysfunction. Hemin enhanced mitochondrial
      biogenesis, as indicated by increased levels of peroxisome proliferator-activated
      receptor-gamma coactivator 1alpha, nuclear respiratory factor 1, and
      mitochondrial transcription factor A (TFAM). Hemin also enhanced mitophagy, as
      indicated by decreased PTEN-induced putative kinase 1 (PINK1) level and increased
      Parkin level. Hemin decreased fission-related protein, dynamin-related protein 1
      (DRP1), and increased fusion-related protein, mitofusin 2. Hemin attenuated the
      increased TLR4 expression. TAK-242, a TLR4 antagonist, attenuated mortality,
      inflammatory response, and impaired mitochondrial QC. Our findings suggest that
      HO-1 attenuates septic injury by modulating TLR4-mediated mitochondrial QC.

PMID- 29028773
TI  - Medication Review and the Active Consumer of Health.

PMID- 29028774
TI  - Seeking Humanizing Care in Patient-Centered Care Process: A Grounded Theory
      Study.
AB  - Patient-centered care is both a goal in itself and a tool for enhancing health
      outcomes. The application of patient-centered care in health care services
      globally however is diverse. This article reports on a study that sought to
      introduce patient-centered care. The aim of this study is to explore the process
      of providing patient-centered care in critical care units. The study used a
      grounded theory method. Data were collected on 5 critical care units in Tehran
      University of Medical Sciences. Purposive and theoretical sampling directed the
      collection of data using 29 semistructured interviews with 27 participants
      (nurses, patients, and physician). Data obtained were analyzed according to the
      analysis stages of grounded theory and constant comparison to identify the
      concepts, context, and process of the study. The core category of this grounded
      theory is "humanizing care," which consisted of 4 interrelated phases, including
      patient acceptance, purposeful patient assessment and identification,
      understanding patients, and patient empowerment. A core category of humanizing
      care integrated the theory. Humanizing care was an outcome and process. Patient
      centered care is a dynamic and multifaceted process provided according to the
      nurses' understanding of the concept. Patient-centered care does not involve
      repeating routine tasks; rather, it requires an all-embracing understanding of
      the patients and showing respect for their values, needs, and preferences.

PMID- 29028775
TI  - The Effect of Progressive Relaxation Exercises on Fatigue and Sleep Quality in
      Individuals With COPD.
AB  - This randomized controlled experimental study was conducted to investigate the
      effect of progressive muscle relaxation exercises on dyspnea, fatigue, and sleep
      quality in individuals with chronic obstructive pulmonary disease. A Descriptive
      Questionnaire and the Chronic Obstructive Pulmonary Disease and Asthma Fatigue
      Scale, Chronic Obstructive Pulmonary Disease and Asthma Sleep Scale and Medical
      Research Council Dyspnea Scale were used for data collection. The decrease in the
      mean dyspnea, fatigue, and sleep scores in the intervention group was
      statistically significantly more pronounced than the patients in the control
      group (P < .05). Progressive relaxation exercises can be implemented to decrease
      the dyspnea, fatigue, and sleep problems seen in patients with moderate and
      advanced chronic obstructive pulmonary disease by nurses working in the clinic.

PMID- 29028776
TI  - The Effect of Music Therapy on Anxiety and Various Physical Findings in Patients
      With COPD in a Pulmonology Service.
AB  - This interventional study was carried out to determine the effect of music
      therapy on anxiety and the various physical findings in patients with chronic
      obstructive pulmonary disease in the pulmonary diseases service. Ninety-six
      patients (28 females, 68 males) of 114 adult patients who were hospitalized
      between November 10, 2013, and March 10, 2014, were included in the study. Ninety
      six patients were separated in 3 groups. The data for the study were collected
      from a questionnaire form of sociodemographic and clinical characteristics, a
      patient follow-up form, and the Beck Anxiety Scale. SPPS 11.5 was used for data
      analysis. The Kolmogorov-Smirnov Test was used to determine whether the data
      showed normal distribution. The nonparametric Kruskal-Wallis Test was used to
      determine the differences between mean anxiety scores on day 0, day 5, and day
      15, and the differences in physiological findings on day 0, day 5, and day 15.
      There was a significant decrease in anxiety level average on day 5 (P <= .0001)
      and day 15 (P <= .0001) of the study in both the Western classical music and
      Turkish classical music groups compared with control group. There was also a
      significant decrease in systolic blood pressure and diastolic blood pressure
      averages in both music groups compared with control group (P <= .005). There was
      no significant difference in heart rates and respiration rate average between the
      Western classical music and Turkish classical music groups compared with the
      control group (P > .05).

PMID- 29028777
TI  - Taboo in the Workplace: A Qualitative Study of Taiwanese Nurses' "Not-Eating
      Pineapple" in Clinical Practice.
AB  - There has been an increased emphasis on nurses' mental health and well-being in
      the workplace. Psychologists have established a correlative link between
      individual's beliefs on luck and mental health. The pineapple taboo has been
      observed among Taiwanese hospital nurses as a prevalent superstitious belief for
      bringing luck or warding off increased clinical workloads, but how and why the
      ritual persists in the hospital workplace remains unknown. This article aims to
      explore the latent meaning of observance of the taboo and how it is related to
      nurses' clinical practice and possibly affects their mental health at work. A
      qualitative research was designed in line with the hermeneutic phenomenological
      method. Through purposive sampling, 18 nurse participants were recruited for in
      depth semistructured interviews. Resulting from the ensuing analysis, 3
      modalities were identified as constituting the spectrum of observance of the
      taboo: (a) "strictly not eating pineapple"; (b) "not eating pineapple at work";
      and (c) "eating pineapple without admitting to doing so." Each reflects the
      position of nurses revealed in relation to the pineapple taboo in clinical
      settings. Based on the subjective narratives of nurses, it may be understood as
      an active moral attempt at "being right" rather than a passive avoidance of bad
      luck in the taboo observation. The findings facilitate an appropriate
      understanding of the embedded meaning of nurses' workplace-related belief and its
      seminal function of empowerment for nurses in holistic nursing practice.

PMID- 29028778
TI  - Essential Oils and Gastroparesis: Power for Transforming Health, Hope, and
      Quality of Life.
AB  - This study explored how essential oils for persons with gastroparesis symptoms
      affect the quality of life. Gastroparesis is a chronic delayed gastric motility
      disorder characterized by postprandial fullness, early satiety, nausea, vomiting,
      abdominal discomfort, bloating, depression, and anxiety. The aim of this study
      was to determine how essential oils support digestion and eliminate inflammation
      in the body as evidenced by self-reporting a decrease in symptoms, thereby
      improving quality of life. A qualitative descriptive methodology using Barrette's
      Theory of Power as Knowing Participation in Change thematic framework was used.
      Three main themes were extracted from the data: awareness of quality of life
      possibilities, freedom to make choices, and transforming health and hope. The
      constitutive theme that was synthesized became essential oils transform health,
      hope, and increase quality-of-life possibilities.

PMID- 29028779
TI  - An Investigation of the Use of Traditional Chinese Medicine and Complementary and
      Alternative Medicine in Stroke Patients.
AB  - This study aimed to investigate the use of traditional Chinese medicine and
      complementary and alternative medicine in stroke patients in Taiwan. Chinese
      herbal medicine, massage, acupuncture, natural products, and exercise were widely
      used among stroke patients. Integrating safe and effective traditional Chinese
      medicine and complementary and alternative medicine into conventional therapies
      is suggested.

PMID- 29028780
TI  - Nutritional Neuroscience: A Therapeutic Lifestyle Factor in Mental Health.

PMID- 29028781
TI  - Fragranced Products and Risks of Adverse Effects.

PMID- 29028782
TI  - Single coronary artery anomaly and chest pain.

PMID- 29028783
TI  - Three-dimensional transesophageal echocardiography in the guide of cardiac mass
      biopsy: future prospectives.

PMID- 29028784
TI  - Manufacturer change and risk of system-related complications after implantable
      cardioverter defibrillator replacement: physicians' survey and data from the
      Detect Long-term Complications After Implantable Cardioverter Defibrillator
      Replacement Registry.
AB  - AIMS: Some barriers seem to exist in changing implantable cardioverter
      defibrillator (ICD) manufacturer at the time of device replacement. We sought to
      understand the obstacles to changing ICD manufacturer within the cohort of
      patients enrolled in the Detect Long-term Complications After ICD Replacement
      Registry. METHODS: We analyzed 784 consecutive ICD/cardiac resynchronization
      therapy defibrillator (CRT-D) device replacements within a 1.5-year time-frame in
      36 Italian centers to evaluate potential factors associated with changing
      manufacturers and system-related complications. RESULTS: Manufacturer change
      occurred in 191 patients (24%): 72/211 single-chamber ICDs (34%), 52/210 dual
      chamber ICDs (25%) and 67/363 CRT-D (18%, P < 0.0001 vs. single-chamber).
      Replacement-only procedures were associated with a lower rate of manufacturer
      change than upgrading procedures (23 vs. 32%, P = 0.02). In the single
      chamber/dual-chamber cohort, the only variables associated with manufacturer
      change were the number of available manufacturers (OR = 1.9; P < 0.0001) and an
      upgrade procedure (OR = 1.7; P = 0.035), whereas the center volume was associated
      with maintenance of the same manufacturer (OR = 0.5; P = 0.0172). In the CRT-D
      group, the number of available manufacturers [OR = 2.9; P < 0.0001, service life
      below the median value (OR = 2.5; P = 0.0026)], and physiological design (OR =
      8.4; P = 0.0048) were associated with manufacturer change. At 6-month follow-up,
      17 patients (2.2%) experienced a system complication that was lead-related in all
      cases; upgrade procedure was the only predictor (hazard ratio = 6.7) of
      complications. CONCLUSION: At the time of ICD replacement, a manufacturer change
      occurred in 24% of patients and it was less likely in CRT-D devices, which are
      equipped with more specific technology and less frequently require the addition
      of features. System-related complications are strongly associated to upgrade
      procedures rather than to manufacturer change.

PMID- 29028785
TI  - A shot through the heart.

PMID- 29028786
TI  - Reducer, extracorporeal shockwave therapy or stem cells in refractory angina: a
      retrospective study.

PMID- 29028787
TI  - Relationship Between PD-L1 Expression and CD8+ T-cell Immune Responses in
      Hepatocellular Carcinoma.
AB  - As PD-1/PD-L1 immune checkpoint inhibitors exhibited promising clinical outcomes
      in various types of solid tumors, PD-1/PD-L1 blockades have been explored for the
      treatment of hepatocellular carcinoma (HCC). However, the association of PD-L1
      with antitumor immunoregulation is not clearly defined in HCC. Here, we evaluated
      the characteristics of PD-L1 expression, CD8 T-cell infiltration and their
      relationship in HCC. A total of 411 resected tumor specimens from HCC patients
      were immunostained for PD-L1 and CD8. Only 78 (19%) cases showed >=5% membranous
      PD-L1 expression on tumor cells, although a significantly positive correlation
      was found between PD-L1 expression and CD8 T-cell densities. Moreover, patients
      with higher tumor PD-L1 expression also showed a higher hepatitis B virus load,
      which was also related to increased CD8 infiltration. Survival analysis suggested
      that both tumor and stroma PD-L1 status did not significantly affect overall
      survival or recurrence-free survival in patients. Although high CD8 T-cell
      density was overall associated with better overall survival and recurrence-free
      survival, its favorable prognostic value was eliminated by high tumor PD-L1
      expression. Further flow cytometric and enzyme-linked immunosorbent assay (ELISA)
      results from the coculture of HCC cell lines with specific CD8 cytotoxic T
      lymphocytes (CTLs) demonstrated that CD8 CTLs remarkably upregulated PD-L1
      expression on tumor cell lines by HLA class-I specificity, and the overexpression
      of tumor PD-L1 impaired interferon-gamma secretion by CD8 CTLs in a negative
      feedback regulation mechanism. In conclusion, our findings reveal an interaction
      between PD-L1 expression and CD8 T-cell immunity in HCC, although PD-L1 is not a
      prognostic factor for the patients.

PMID- 29028788
TI  - Efficacy and Safety of Pembrolizumab in Patients Enrolled in KEYNOTE-030 in the
      United States: An Expanded Access Program.
AB  - KEYNOTE-030 (ClinicalTrials.gov ID, NCT02083484) was a global expanded access
      program that allowed access to pembrolizumab, an antiprogrammed death 1 antibody,
      for patients with advanced melanoma before its regulatory approval. Patients with
      unresectable stage III/IV melanoma that progressed after standard-of-care
      therapy, including ipilimumab and, if BRAF mutant, a BRAF inhibitor, were
      eligible to receive pembrolizumab 2 mg/kg every 3 weeks. Response was assessed by
      immune-related response criteria by investigator review. Adverse events (AEs)
      were graded according to the National Cancer Institute Common Terminology
      Criteria for Adverse Events, version 4.0. In the United States, 979 patients
      enrolled between April and September 2014. Of the 947 evaluable patients, 621
      (65.6%) remained on treatment and transitioned to receive commercial
      pembrolizumab following approval by the Food and Drug Administration, whereas 326
      (34.4%) discontinued, most commonly for disease progression (39.6%) or death
      (26.4%). Objective response rate was 14.5% (95% confidence interval, 12.2%-16.8%)
      in the treated population (n=947) and 22.1% (95% confidence interval, 18.8%
      25.5%) in patients who had >=1 response assessment reported (n=619). Twelve
      patients achieved complete response. One hundred eighty-one (19.1%) patients
      experienced >=1 treatment-related AE, most commonly general disorders (8.0%),
      skin/subcutaneous tissue disorders (7.3%), and gastrointestinal disorders (6.4%);
      29 (3.1%) patients experienced >=1 grade 3/4 treatment-related AE. Immune
      mediated AEs were also reported. There were no treatment-related deaths. The
      safety and efficacy observed in this expanded access program were consistent with
      those previously reported for similar populations and support the use of
      pembrolizumab for patients with advanced melanoma.

PMID- 29028789
TI  - Safe Administration of An Anti-PD-1 Antibody to Kidney-transplant Patients: 2
      Clinical Cases and Review of the Literature.
AB  - Antiprogrammed cell-death protein 1 (PD-1) antibodies have revolutionized therapy
      of metastatic melanoma and other tumors, but some subgroups of patients such as
      immunosuppressed patients after solid-organ transplantation, have regularly been
      excluded from clinical studies. We report 2 cases of kidney-transplant patients
      who received an anti-PD-1 antibody to treat metastatic melanoma. Treatment was
      tolerated well with no relevant adverse events and stable kidney functions, but
      the melanoma progressed in both patients. Factors potentially affecting risk of
      allograft rejection and response to treatment, for example, immunosuppressive
      regimen and therapeutic sequence, are discussed on the basis of current
      literature. Further studies are necessary to determine the risk of allograft
      rejection and the therapeutic benefit of anti-PD-1 antibodies for organ
      transplanted patients, in particular as these checkpoint inhibitors have become
      therapeutic standard in a variety of tumors other than melanoma.

PMID- 29028790
TI  - Imaging Factors that Distinguish Between Patients with Asymptomatic and
      Symptomatic Cervical Spondylotic Myelopathy with Mild to Moderate Cervical Spinal
      Cord Compression.
AB  - BACKGROUND Not all patients with spinal cord compression due to cervical
      spondylotic myelopathy (CSM) have clinical symptoms and signs. The aim of this
      study was to investigate and compare the imaging findings in asymptomatic and
      symptomatic patients with CSM with mild to moderate cervical spinal cord
      compression. MATERIAL AND METHODS A retrospective clinical study included 68
      patients. Group A (n=30) had no symptoms and signs; group B (n=38) had symptoms
      and signs of cervical myelopathy. The age, sex, body mass index (BMI), history of
      steroid treatment, duration of symptoms, number of spondylotic cervical segments,
      Torg ratio, range of motion (ROM), incidence of cervical segmental instability,
      overall curvature of the cervical spine, direction of spinal cord compression,
      and spinal cord magnetic resonance imaging (MRI) signal intensity were compared.
      RESULTS For groups A and B, the Torg ratio was 90.3% and 83.6% (P<0.05), the
      incidence of cervical segmental instability was 23.3% and 65.8% (P<0.05), and the
      incidence of a spinal cord high intensity signal was 13.3% and 86.9% (P<0.05).
      Logistic regression analysis showed myelopathy as a dependent variable,
      independently associated with cervical segmental instability (OR=5.898, P=0.037),
      an MRI T2-weighted intramedullary high signal (OR=9.718, P=0.002), and Torg ratio
      (OR=0.155, P=0.006). CONCLUSIONS Cervical segmental instability, a high
      intramedullary signal on T2-weighted MRI, and the Torg ratio had the greatest
      capacity to distinguish between asymptomatic and symptomatic patients with CSM
      with mild to moderate cervical spinal cord compression.

PMID- 29028791
TI  - Is diacerein an alternative for the treatment of osteoarthritis?
AB  - INTRODUCTION: Among the possibilities for the management of osteoarthritis,
      different pharmacological alternatives have been proposed, being diacerein one of
      them due to its anti-inflammatory effect. However, diacerein clinical utility is
      not clear. METHODS: To answer this question, we used Epistemonikos, the largest
      database of systematic reviews in health, which is maintained by screening
      multiple information sources, including MEDLINE, EMBASE, Cochrane, among others.
      We extracted data from the systematic reviews, reanalyzed data of primary
      studies, conducted a meta-analysis and generated a summary of findings table
      using the GRADE approach. RESULTS AND CONCLUSION: We concluded diacerein probably
      leads to a slight reduction in pain, but would not improve functionality among
      patients with knee osteoarthritis, and can frequently present diarrhea as an
      adverse effect.

PMID- 29028792
TI  - Is a psychotherapeutic approach possible in primary health care?
AB  - The development of valid psychotherapeutic approaches, adapted to the
      characteristics of the consultation in primary care, is a subject in constant
      development. In order to work effectively in a model of psychotherapy adjusted to
      primary care, the health practitioner (psychiatrist, psychologist, or family
      physician) must constantly focus on finding the most efficient way to treat the
      patient, in a short period of time, and with different nuances from those usually
      used in secondary care: That is, an eclectic and pragmatic approach to dealing
      with the problems that patients bring to consultation, and a practical and direct
      way of assisting them, in order to achieve therapeutic goals. To try to answer
      the question of whether it is possible to perform psychotherapeutic approaches in
      primary health care, this brief analysis presents a reflection on the issue and a
      case example.

PMID- 29028793
TI  - Clinico-pathological features of erythema nodosum leprosum: A case-control study
      at ALERT hospital, Ethiopia.
AB  - BACKGROUND: Leprosy reactions are a significant cause of morbidity in leprosy
      population. Erythema nodosum leprosum (ENL) is an immunological complication
      affecting approximately 50% of patients with lepromatous leprosy (LL) and 10% of
      borderline lepromatous (BL) leprosy. ENL is associated with clinical features
      such as skin lesions, neuritis, arthritis, dactylitis, eye inflammation,
      osteitis, orchitis, lymphadenitis and nephritis. ENL is treated mainly with
      corticosteroids and corticosteroids are often required for extended periods of
      time which may lead to serious adverse effects. High mortality rate and increased
      morbidity associated with corticosteroid treatment of ENL has been reported. For
      improved and evidence-based treatment of ENL, documenting the systems affected by
      ENL is important. We report here the clinical features of ENL in a cohort of
      patients with acute ENL who were recruited for a clinico-pathological study
      before and after prednisolone treatment. MATERIALS AND METHODS: A case-control
      study was performed at ALERT hospital, Ethiopia. Forty-six LL patients with ENL
      and 31 non-reactional LL matched controls were enrolled to the study and followed
      for 28 weeks. Clinical features were systematically documented at three visits
      (before, during and after predinsolone treatment of ENL cases) using a
      specifically designed form. Skin biopsy samples were obtained from each patient
      before and after treatment and used for histopathological investigations to
      supplement the clinical data. RESULTS: Pain was the most common symptom reported
      (98%) by patients with ENL. Eighty percent of them had reported skin pain and
      more than 70% had nerve and joint pain at enrolment. About 40% of the patients
      developed chronic ENL. Most individuals 95.7% had nodular skin lesions. Over half
      of patients with ENL had old nerve function impairment (NFI) while 13% had new
      NFI at enrolment. Facial and limb oedema were present in 60% patients. Regarding
      pathological findings before treatment, dermal neutrophilic infiltration was
      noted in 58.8% of patients with ENL compared to 14.3% in LL controls. Only 14.7%
      patients with ENL had evidence of vasculitis at enrolment. CONCLUSION: In our
      study, painful nodular skin lesions were present in all ENL patients. Only 58%
      patients had dermal polymorphonuclear cell infiltration showing that not all
      clinically confirmed ENL cases have neutrophilic infiltration in lesions. Very
      few patients had histological evidence of vasculitis. Many patients developed
      chronic ENL and these patients require inpatient corticosteroid treatment for
      extended periods which challenges the health service facility in resource poor
      settings, as well as the patient's quality of life.

PMID- 29028795
TI  - Alx4 relays sequential FGF signaling to induce lacrimal gland morphogenesis.
AB  - The sequential use of signaling pathways is essential for the guidance of
      pluripotent progenitors into diverse cell fates. Here, we show that Shp2
      exclusively mediates FGF but not PDGF signaling in the neural crest to control
      lacrimal gland development. In addition to preventing p53-independent apoptosis
      and promoting the migration of Sox10-expressing neural crests, Shp2 is also
      required for expression of the homeodomain transcription factor Alx4, which
      directly controls Fgf10 expression in the periocular mesenchyme that is necessary
      for lacrimal gland induction. We show that Alx4 binds an Fgf10 intronic element
      conserved in terrestrial but not aquatic animals, underlying the evolutionary
      emergence of the lacrimal gland system in response to an airy environment.
      Inactivation of ALX4/Alx4 causes lacrimal gland aplasia in both human and mouse.
      These results reveal a key role of Alx4 in mediating FGF-Shp2-FGF signaling in
      the neural crest for lacrimal gland development.

PMID- 29028794
TI  - Condensin II and GAIT complexes cooperate to restrict LINE-1 retrotransposition
      in epithelial cells.
AB  - LINE-1 (L1) retrotransposons can mobilize (retrotranspose) within the human
      genome, and mutagenic de novo L1 insertions can lead to human diseases, including
      cancers. As a result, cells are actively engaged in preventing L1
      retrotransposition. This work reveals that the human Condensin II complex
      restricts L1 retrotransposition in both non-transformed and transformed cell
      lines through inhibition of L1 transcription and translation. Condensin II
      subunits, CAP-D3 and CAP-H2, interact with members of the Gamma-Interferon
      Activated Inhibitor of Translation (GAIT) complex including the glutamyl-prolyl
      tRNA synthetase (EPRS), the ribosomal protein L13a, Glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH), and NS1 associated protein 1 (NSAP1). GAIT has been shown
      to inhibit translation of mRNAs encoding inflammatory proteins in myeloid cells
      by preventing the binding of the translation initiation complex, in response to
      Interferon gamma (IFN-gamma). Excitingly, our data show that Condensin II
      promotes complexation of GAIT subunits. Furthermore, RNA-Immunoprecipitation
      experiments in epithelial cells demonstrate that Condensin II and GAIT subunits
      associate with L1 RNA in a co-dependent manner, independent of IFN-gamma. These
      findings suggest that cooperation between the Condensin II and GAIT complexes may
      facilitate a novel mechanism of L1 repression, thus contributing to the
      maintenance of genome stability in somatic cells.

PMID- 29028797
TI  - STAT, Wingless, and Nurf-38 determine the accuracy of regeneration after
      radiation damage in Drosophila.
AB  - We report here a study of regeneration in Drosophila larval wing imaginal discs
      after damage by ionizing radiation. We detected faithful regeneration that
      restored a wing disc and abnormal regeneration that produced an extra wing disc.
      We describe a sequence of changes in cell number, location and fate that occur to
      produce an ectopic disc. We identified a group of cells that not only participate
      in ectopic disc formation but also recruit others to do so. STAT92E (Drosophila
      STAT3/5) and Nurf-38, which encodes a member of the Nucleosome Remodeling Factor
      complex, oppose each other in these cells to modulate the frequency of ectopic
      disc growth. The picture that emerges is one in which activities like STAT
      increase after radiation damage and fulfill essential roles in rebuilding the
      tissue. But such activities must be kept in check so that one and only one wing
      disc is regenerated.

PMID- 29028796
TI  - BAK1 is involved in AtRALF1-induced inhibition of root cell expansion.
AB  - The rapid alkalinization factor (RALF) peptide negatively regulates cell
      expansion, and an antagonistic relationship has been demonstrated between
      AtRALF1, a root-specific RALF isoform in Arabidopsis, and brassinosteroids (BRs).
      An evaluation of the response of BR signaling mutants to AtRALF1 revealed that
      BRI1-associated receptor kinase1 (bak1) mutants are insensitive to AtRALF1 root
      growth inhibition activity. BAK1 was essential for the induction of AtRALF1
      responsive genes but showed no effect on the mobilization of Ca2+ and
      alkalinization responses. Homozygous plants accumulating AtRALF1 and lacking the
      BAK1 gene did not exhibit the characteristic semi-dwarf phenotype of AtRALF1
      overexpressors. Biochemical evidence indicates that AtRALF1 and BAK1 physically
      interact with a Kd of 4.6 MUM and acridinium-labeled AtRALF1 was used to
      demonstrate that part of the specific binding of AtRALF1 to intact seedlings and
      to a microsomal fraction derived from the roots of Arabidopsis plants is BAK1
      dependent. Moreover, AtRALF1 induces an increase in BAK1 phosphorylation,
      suggesting that the binding of AtRALF1 to BAK1 is functional. These findings show
      that BAK1 contains an additional AtRALF1 binding site, indicating that this
      protein may be part of a AtRALF1-containing complex as a co-receptor, and it is
      required for the negative regulation of cell expansion.

PMID- 29028798
TI  - Obstructive sleep apnea and rhonchopathy are associated with downregulation of
      trefoil factor family peptide 3 (TFF3)-Implications of changes in oral mucus
      composition.
AB  - STUDY OBJECTIVES: Trefoil factor family (TFF) peptides belong to the family of
      mucin-associated peptides and are expressed in most mucosal surfaces. TFF
      peptides carry out functions such as proliferation and migration enhancement,
      anti-apoptosis, and wound healing. Moreover, TFFs are associated with mucins and
      interact with them as "linker peptides", thereby influencing mucus viscosity. To
      test the hypothesis that in rhonchopathy and obstructive sleep apnea (OSA)
      changes occur in the expression of TFF3 and -2 that could contribute to changes
      in mucus viscosity, leading to an increase in upper airway resistance during
      breathing. METHODS: RT-PCR, Western-blot, immunohistochemistry and ELISA were
      performed to detect and quantify TFF3 and -2 in uvula samples. In addition, 99
      saliva samples from patients with mild, moderate or severe OSA, as well as
      samples from rhonchopathy patients and from healthy volunteers, were analyzed by
      ELISA. RESULTS: TFF3 was detected in all uvula samples. Immunohistochemistry
      revealed a subjectively decreasing antibody reactivity of the uvula epithelia
      with increasing disease severity. ELISA demonstrated significantly higher TFF3
      saliva protein concentrations in the healthy control group compared to cases with
      rhonchopathy and OSA. Predisposing factors of OSA such as BMI or age showed no
      correlation with TFF3. No significant changes were observed with regard to TFF2.
      CONCLUSIONS: The results suggest the involvement of TFF3 in the pathogenesis of
      rhonchopathy and OSA and lead to the hypothesis that reduction of TFF3 production
      by the epithelium and subepithelial mucous glands of the uvula contribute to an
      increase in breathing resistance due to a change in mucus organization.

PMID- 29028799
TI  - Modeling the environmental suitability of anthrax in Ghana and estimating
      populations at risk: Implications for vaccination and control.
AB  - Anthrax is hyper-endemic in West Africa. Despite the effectiveness of livestock
      vaccines in controlling anthrax, underreporting, logistics, and limited resources
      makes implementing vaccination campaigns difficult. To better understand the
      geographic limits of anthrax, elucidate environmental factors related to its
      occurrence, and identify human and livestock populations at risk, we developed
      predictive models of the environmental suitability of anthrax in Ghana. We
      obtained data on the location and date of livestock anthrax from veterinary and
      outbreak response records in Ghana during 2005-2016, as well as livestock
      vaccination registers and population estimates of characteristically high-risk
      groups. To predict the environmental suitability of anthrax, we used an ensemble
      of random forest (RF) models built using a combination of climatic and
      environmental factors. From 2005 through the first six months of 2016, there were
      67 anthrax outbreaks (851 cases) in livestock; outbreaks showed a seasonal peak
      during February through April and primarily involved cattle. There was a median
      of 19,709 vaccine doses [range: 0-175 thousand] administered annually. Results
      from the RF model suggest a marked ecological divide separating the broad areas
      of environmental suitability in northern Ghana from the southern part of the
      country. Increasing alkaline soil pH was associated with a higher probability of
      anthrax occurrence. We estimated 2.2 (95% CI: 2.0, 2.5) million livestock and 805
      (95% CI: 519, 890) thousand low income rural livestock keepers were located in
      anthrax risk areas. Based on our estimates, the current anthrax vaccination
      efforts in Ghana cover a fraction of the livestock potentially at risk, thus
      control efforts should be focused on improving vaccine coverage among high risk
      groups.

PMID- 29028800
TI  - Spatial distribution of extensively drug-resistant tuberculosis (XDR TB) patients
      in KwaZulu-Natal, South Africa.
AB  - BACKGROUND: KwaZulu-Natal province, South Africa, has among the highest burden of
      XDR TB worldwide with the majority of cases occurring due to transmission. Poor
      access to health facilities can be a barrier to timely diagnosis and treatment of
      TB, which can contribute to ongoing transmission. We sought to determine the
      geographic distribution of XDR TB patients and proximity to health facilities in
      KwaZulu-Natal. METHODS: We recruited adults and children with XDR TB diagnosed in
      KwaZulu-Natal. We calculated distance and time from participants' home to the
      closest hospital or clinic, as well as to the actual facility that diagnosed XDR
      TB, using tools within ArcGIS Network analyst. Speed of travel was assigned to
      road classes based on Department of Transport regulations. Results were compared
      to guidelines for the provision of social facilities in South Africa: 5km to a
      clinic and 30km to a hospital. RESULTS: During 2011-2014, 1027 new XDR TB cases
      were diagnosed throughout all 11 districts of KwaZulu-Natal, of whom 404 (39%)
      were enrolled and had geospatial data collected. Participants would have had to
      travel a mean distance of 2.9 km (CI 95%: 1.8-4.1) to the nearest clinic and 17.6
      km (CI 95%: 11.4-23.8) to the nearest hospital. Actual distances that
      participants travelled to the health facility that diagnosed XDR TB ranged from
      <10 km (n = 143, 36%) to >50 km (n = 109, 27%), with a mean of 69 km. The
      majority (77%) of participants travelled farther than the recommended distance to
      a clinic (5 km) and 39% travelled farther than the recommended distance to a
      hospital (30 km). Nearly half (46%) of participants were diagnosed at a health
      facility in eThekwini district, of whom, 36% resided outside the Durban
      metropolitan area. CONCLUSIONS: XDR TB cases are widely distributed throughout
      KwaZulu-Natal province with a denser focus in eThekwini district. Patients
      travelled long distances to the health facility where they were diagnosed with
      XDR TB, suggesting a potential role for migration or transportation in the XDR TB
      epidemic.

PMID- 29028802
TI  - Pneumococcal responses are similar in Papua New Guinean children aged 3-5 years
      vaccinated in infancy with pneumococcal polysaccharide vaccine with or without
      prior pneumococcal conjugate vaccine, or without pneumococcal vaccination.
AB  - TRIAL DESIGN: In an earlier trial, Papua New Guinean (PNG) children at high risk
      of pneumococcal disease were randomized to receive 0 or 3 doses of 7-valent
      pneumococcal conjugate vaccine (PCV7), followed by a single dose of 23-valent
      pneumococcal polysaccharide vaccine (PPV23) at 9 months of age. We here studied
      in a non-randomized follow-up trial the persistence of pneumococcal immunity in
      these children at 3-5 years of age (n = 132), and in 121 community controls of a
      similar age with no prior pneumococcal vaccination. METHODS: Circulating IgG
      antibody titers to all PCV7 and PPV23-only serotypes 2, 5 and 7F were measured
      before and after challenge with 1/5th of a normal PPV23 dose. Serotype-specific
      memory B-cells were enumerated at 10 months and 3-5 years of age for a subgroup
      of study children. RESULTS: Serotype-specific IgG antibody titers before and
      after challenge were similar for children who received PCV7/PPV23, PPV23 only, or
      no pneumococcal vaccines. Before challenge, at least 89% and 59% of children in
      all groups had serotype-specific titers >= 0.35MUg/ml and >= 1.0 MUg/ml,
      respectively. Post-challenge antibody titers were higher or similar to pre
      challenge titers for most children independent of pneumococcal vaccination
      history. The rise in antibody titers was significantly lower when pre-challenge
      titers were higher. Overall the relative number of serotype-specific memory B
      cells remained the same or increased between 10 months and 3-5 years of age, and
      there were no differences in serotype-specific memory B-cell numbers at 3-5 years
      of age between the three groups. CONCLUSIONS: Immunity induced by PCV7 and/or
      PPV23 immunization in infancy does not exceed that of naturally acquired immunity
      in 3-5-year-old children living in a highly endemic area. Also, there was no
      evidence that PPV23 immunization in the first year of life following PCV7 priming
      induces longer-term hypo-responsiveness. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT01414504 and NCT00219401.

PMID- 29028801
TI  - dOCRL maintains immune cell quiescence by regulating endosomal traffic.
AB  - Lowe Syndrome is a developmental disorder characterized by eye, kidney, and
      neurological pathologies, and is caused by mutations in the phosphatidylinositol
      5-phosphatase OCRL. OCRL plays diverse roles in endocytic and endolysosomal
      trafficking, cytokinesis, and ciliogenesis, but it is unclear which of these
      cellular functions underlie specific patient symptoms. Here, we show that
      mutation of Drosophila OCRL causes cell-autonomous activation of hemocytes, which
      are macrophage-like cells of the innate immune system. Among many cell biological
      defects that we identified in docrl mutant hemocytes, we pinpointed the cause of
      innate immune cell activation to reduced Rab11-dependent recycling traffic and
      concomitantly increased Rab7-dependent late endosome traffic. Loss of docrl
      amplifies multiple immune-relevant signals, including Toll, Jun kinase, and STAT,
      and leads to Rab11-sensitive mis-sorting and excessive secretion of the Toll
      ligand Spatzle. Thus, docrl regulation of endosomal traffic maintains hemocytes
      in a poised, but quiescent state, suggesting mechanisms by which endosomal
      misregulation of signaling may contribute to symptoms of Lowe syndrome.

PMID- 29028803
TI  - Scale of Body Connection: A multi-sample construct validation study.
AB  - The Scale of Body Connection (SBC) was created to address the need for a self
      report measure to examine body awareness and bodily dissociation in mind-body
      research. Developed in the U.S.A., it has been translated into many languages and
      tested for validity of scale translation. The burgeoning of mind-body research
      and the widespread use of the SBC scale underscored the need for critical
      assessment of the instrument's measurement properties. Thus, a broader evaluation
      of the SBC was designed using large samples from eight international, cross
      sectional studies drawn from community (i.e., non-clinical) populations.
      Specifically, we assessed scale distribution properties and internal consistency
      reliabity, and using confirmatory factory analysis we evaluated scale contruct
      validity and compared male/female measurement models. The results indicated
      acceptable reliability for both the body awareness and bodily dissociation
      scales, and a good fit between the proposed theoretic model and the data,
      providing evidence of construct validity across all samples. Mean differences in
      body awareness were observed for males vs. females in most samples, with females
      generally showing higher body awareness compared to males. Multi-group structural
      equation modeling demonstrated a stable latent factor structure and factor
      loadings, indicating equivalent measurement models for males and females. In
      summary, this multi-sample study demonstrated SBC construct validity that
      supports its use in clinical research as a brief, readily translated, easy to
      administer measure of body awareness and bodily dissociation.

PMID- 29028804
TI  - A recombinase polymerase amplification assay for rapid detection of Crimean-Congo
      Haemorrhagic fever Virus infection.
AB  - BACKGROUND: Crimean-Congo Haemorrhagic fever Virus (CCHFV) is a rapidly emerging
      vector-borne pathogen and the cause of a virulent haemorrhagic fever affecting
      large parts of Europe, Africa, the Middle East and Asia. METHODOLOGY/PRINCIPLE
      FINDINGS: An isothermal recombinase polymerase amplification (RPA) assay was
      successfully developed for molecular detection of CCHFV. The assay showed rapid
      (under 10 minutes) detection of viral extracts/synthetic virus RNA of all 7 S
      segment clades of CCHFV, with high target specificity. The assay was shown to
      tolerate the presence of inhibitors in crude preparations of mock field samples,
      indicating that this assay may be suitable for use in the field with minimal
      sample preparation. The CCHFV RPA was successfully used to screen and detect
      CCHFV positives from a panel of clinical samples from Tajikistan.
      CONCLUSIONS/SIGNIFICANCE: The assay is a rapid, isothermal, simple-to-perform
      molecular diagnostic, which can be performed on a light, portable real-time
      detection device. It is ideally placed therefore for use as a field-diagnostic or
      in-low resource laboratories, for monitoring of CCHF outbreaks at the point-of
      need, such as in remote rural regions in affected countries.

PMID- 29028805
TI  - What drives slow wave activity during early non-REM sleep: Learning during prior
      wake or effort?
AB  - What is the function of sleep in humans? One claim is that sleep consolidates
      learning. Slow wave activity (SWA), i.e. slow oscillations of frequency < 4 Hz,
      has been observed in electroencephalograms (EEG) during sleep; it increases with
      prior wakefulness and decreases with sleep. Studies have claimed that increase in
      SWA in specific regions of the sleeping brain is correlated with overnight
      improved performance, i.e. overnight consolidation, on a demanding motor learning
      task. We wondered if SWA change during sleep is attributable to overnight
      consolidation or to metabolic demand. Participants executed out-and-back
      movements to a target using a pen-like cursor with their dominant hand while the
      target and cursor position were displayed on a screen. They trained on three
      different conditions on separate nights, differing in the amount and degree of
      rotation between the actual hand movement direction and displayed cursor movement
      direction. In the no-rotation (NR) condition, there was no rotation. In the
      single rotation (SR) condition, the amount of rotation remained the same
      throughout, and performance improved both across pre-sleep training and after
      sleep, i.e. overnight consolidation occurred; in the random rotation (RR)
      condition, the amount of rotation varied randomly from trial to trial, and no
      overnight consolidation occurred; SR and RR were cognitively demanding. The
      average EEG power density of SWA for the first 30 min. of non-rapid eye movement
      sleep after training was computed. Both SR and RR elicited increase in SWA in the
      parietal region; furthermore, the topographic distribution of SWA in each was
      remarkably similar. No correlation was found between the overnight performance
      improvement on SR and the SWA change in the parietal region on measures of
      learning. Our results argue that regulation of SWA in early sleep is associated
      with high levels of cognitive effort during prior wakefulness, and not just
      overnight consolidation.

PMID- 29028806
TI  - A novel immunotoxin reveals a new role for CD321 in endothelial cells.
AB  - There are currently several antibody therapies that directly target tumors, and
      antibody-drug conjugates represent a novel moiety as next generation
      therapeutics. Here, we used a unique screening probe, DT3C, to identify
      functional antibodies that recognized surface molecules and functional epitopes,
      and which provided toxin delivery capability. Accordingly, we generated the 90G4
      antibody, which induced DT3C-dependent cytotoxicity in endothelial cells.
      Molecular analysis revealed that 90G4 recognized CD321, a protein localized at
      tight junctions. Although CD321 plays a pivotal role in inflammation and
      lymphocyte trans-endothelial migration, little is known about its mechanism of
      action in endothelial cells. Targeting of CD321 by the 90G4 immunotoxin induced
      cell death. Moreover, 90G4 immunotoxin caused cytotoxicity primarily in migratory
      endothelial cells, but not in those forming sheets, suggesting a critical role
      for CD321 in tumor angiogenesis. We also found that hypoxia triggered
      redistribution of CD321 to a punctate localization on the basal side of cells,
      resulting in functional impairment of tight junctions and increased motility.
      Thus, our findings raise the intriguing possibility that endothelial CD321
      presented cellular localization in tight junction as well as multifunctional
      dynamics in several conditions, leading to illuminate the importance of widely
      expressed CD321 as a potential target for antitumor therapy.

PMID- 29028807
TI  - Ulcerative colitis, Crohn's disease, and irritable bowel syndrome have different
      profiles of extracellular matrix turnover, which also reflects disease activity
      in Crohn's disease.
AB  - BACKGROUND: Increased protease activity is a key pathological feature of
      inflammatory bowel disease (IBD). However, the differences in extracellular
      matrix remodelling (ECM) in Crohn's disease (CD) and ulcerative colitis (UC) are
      not well described. An increased understanding of the inflammatory processes may
      provide optimized disease monitoring and diagnostics. We investigated the tissue
      remodelling in IBD and IBS patients by using novel blood-based biomarkers
      reflecting ECM remodelling. METHODS: Five ECM biomarkers (VICM, BGM, EL-NE, C5M,
      Pro-C5) were measured by competitive ELISAs in serum from 72 CD patients, 60 UC
      patients, 22 patients with irritable bowel syndrome (IBS), and 24 healthy donors.
      One-way analysis of variance, Mann-Whitney U-test, logistic regression models,
      and receiver operator characteristics (ROC) curve analysis was carried out to
      evaluate the diagnostic accuracy of the biomarkers. RESULTS: The ECM remodelling
      was significantly different in UC compared to CD. The best biomarker combination
      to differentiate UC from CD and colonic CD was BGM and VICM (AUC = 0.98, P<0.001;
      AUC = 0.97, P<0.001), and the best biomarker combination to differentiate IBD
      from IBS patients were BGM, EL-NE, and Pro-C5 (AUC = 0.8, P<0.001). When
      correcting for the use of immunosuppressant and elevated CRP levels (CRP>5mg/mL),
      correlation of Pro-C5 (r = 0.36) with CDAI was slightly improved compared to CRP
      (r = 0.27) corrected for the use of immunosuppressant. Furthermore, BGM and EL-NE
      biomarkers were highly associated with colon inflammation in CD patients.
      CONCLUSION: ECM fragments of tissue remodelling in IBD affect UC and CD
      differently, and may aid in differentiating IBD from IBS (EL-NE, BGM, Pro-C5),
      and UC from CD patients (BGM, VICM). Formation of type V collagen is related to
      the level of inflammation in CD and may reflect disease activity in CD.

PMID- 29028808
TI  - Functional characterization of GABAA receptor-mediated modulation of cortical
      neuron network activity in microelectrode array recordings.
AB  - The numerous gamma-aminobutyric acid type A receptor (GABAAR) subtypes are
      differentially expressed and mediate distinct functions at neuronal level. In
      this study we have investigated GABAAR-mediated modulation of the spontaneous
      activity patterns of primary neuronal networks from murine frontal cortex by
      characterizing the effects induced by a wide selection of pharmacological tools
      at a plethora of activity parameters in microelectrode array (MEA) recordings.
      The basic characteristics of the primary cortical neurons used in the recordings
      were studied in some detail, and the expression levels of various GABAAR subunits
      were investigated by western blotting and RT-qPCR. In the MEA recordings, the pan
      GABAAR agonist muscimol and the GABABR agonist baclofen were observed to mediate
      phenotypically distinct changes in cortical network activity. Selective
      augmentation of alphabetagamma GABAAR signaling by diazepam and of delta
      containing GABAAR (delta-GABAAR) signaling by DS1 produced pronounced changes in
      the majority of the activity parameters, both drugs mediating similar patterns of
      activity changes as muscimol. The apparent importance of delta-GABAAR signaling
      for network activity was largely corroborated by the effects induced by the
      functionally selective delta-GABAAR agonists THIP and Thio-THIP, whereas the
      delta-GABAAR selective potentiator DS2 only mediated modest effects on network
      activity, even when co-applied with low THIP concentrations. Interestingly,
      diazepam exhibited dramatically right-shifted concentration-response
      relationships at many of the activity parameters when co-applied with a trace
      concentration of DS1 compared to when applied alone. In contrast, the potencies
      and efficacies displayed by DS1 at the networks were not substantially altered by
      the concomitant presence of diazepam. In conclusion, the holistic nature of the
      information extractable from the MEA recordings offers interesting insights into
      the contributions of various GABAAR subtypes/subgroups to cortical network
      activity and the putative functional interplay between these receptors in these
      neurons.

PMID- 29028810
TI  - Risk of exacerbation following pneumonia in adults with heart failure or chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Recent evidence demonstrates increased short-term risk of cardiac
      complications and respiratory failure among patients with heart failure (HF) and
      chronic obstructive pulmonary disease (COPD), respectively, concurrent with an
      episode of community-acquired pneumonia (CAP). We evaluated patients with pre
      existing HF or COPD, beginning 30 days after CAP diagnosis, to determine if CAP
      had a prolonged impact on their underlying comorbidity. METHODS: A retrospective
      matched-cohort design using US healthcare claims was employed. In each month of
      accrual, patients with HF or COPD who developed CAP ("CAP patients") were matched
      (1:1, without replacement, on demographic and clinical profiles) to patients with
      HF or COPD who did not develop CAP ("comparison patients"). All patients were
      aged >=40 years, and were pneumonia free during prior 1-year period. Exacerbation
      beginning 30 days after the CAP diagnosis and for the subsequent 1-year period
      were compared between CAP and comparison patients. FINDINGS: 38,010 (4.6%) HF
      patients and 48,703 (5.9%) COPD patients experienced a new CAP episode requiring
      hospitalization or outpatient care only, and were matched to comparison patients.
      In the HF subset, CAP patients were 47.2% more likely to experience an
      exacerbation vs patients without CAP (17.8% vs. 12.1%; p<0.001); in the COPD
      subset, CAP patients were 42.3% more likely to experience an exacerbation (16.2%
      vs. 11.4%; p<0.001). CONCLUSIONS: Our data provide evidence that CAP foreshadows
      a prolonged increase in risk of exacerbation of underlying HF or COPD in adults,
      and suggests a potential benefit to CAP prevention strategies.

PMID- 29028809
TI  - Nasal DNA methylation differentiates corticosteroid treatment response in
      pediatric asthma: A pilot study.
AB  - BACKGROUND: Treatment response to systemic corticosteroid in asthmatic children
      is heterogeneous and may be mediated by epigenetic mechanism(s). We aim to
      identify DNA methylation (DNAm) changes responsive to steroid, and DNAm
      biomarkers that distinguish treatment response. MATERIALS AND METHODS: We
      followed 33 children (ages 5-18) presenting to the Emergency Department (ED) for
      asthma exacerbation. Based on whether they met discharge criteria in <=24 hours,
      participants were grouped into good and poor responders to steroid treatment.
      Nasal samples were collected upon presentation to the ED (T0) and 18-24 hours
      later (T1). Genome-wide DNAm was measured for both time points in 20 subjects,
      and compared between T0 and T1 in good and poor responders respectively. DNAm at
      T1 was also compared between two responder groups. DNAm of selected CpGs was
      verified in the complete cohort, and expression of associated genes was examined.
      Interactions between DNAm, common single nucleotide polymorphism (SNP) located at
      the CpG sites and treatment responses were assessed. RESULTS: Three CpGs located
      in the OTX2 promoter showed responder-specific DNAm changes from T0 to T1, in
      which DNAm decreased in good but not in poor responders. Good and poor responders
      showed differential DNAm at T1 in 127 CpGs without and 182 CpGs with common SNP
      co-localization. Negative correlations between DNAm and gene expression were
      observed at CpGs located within the LDHC promoter, suggesting an impact of DNAm
      on gene regulation. Interactions between SNPs, DNAm and treatment response were
      detected. CONCLUSION: Acute systemic steroid treatment modifies nasal DNAm in
      good responders. Nasal DNAm, dependent or independent of SNPs, can differentiate
      response to treatment in acute asthmatic children.

PMID- 29028811
TI  - Elevated expression of HSP10 protein inhibits apoptosis and associates with poor
      prognosis of astrocytoma.
AB  - Astrocytoma is the most common type of primary malignant brain tumor, with pretty
      lowly 5-year survival rate in patients. Although extended surgical removal of the
      tumor and postoperative chemotherapy/radiotherapy executed, still there is large
      recurrence rate, mainly because diffuse glioma tumor cells ubiquitously
      infiltrate into normal parenchyma. So it becomes a priority to hunt novel
      molecular and signaling pathway targets to suppress astrocyma progression. HSP10,
      an important member of Heat shock proteins (Hsps) family, classically works as
      molecular chaperone folding or degradating of target proteins. Evolutionarily,
      HSP10 is also reported to be involved in immunomodulation and tumor progression.
      Poly (ADP-ribose) polymerase (PARP), important in DNA repair, is one of the main
      cleavage targets of caspase. And cleaved PARP (c-PARP) can serve as a marker of
      cells undergoing apoptosis. So far, whether the expression of HSP10 or c-PARP is
      associated with clinicopathologic implication for astrocytoma has not been
      reported. Meanwhile, it is unclear about the relationship between HSP10 and cell
      apoptosis. The purpose of this research is to elucidate the association between
      the expression of HSP10 and c-PARP and clinicopathological characteristics of
      astrocytoma by immunohistochemistry. The results showed that positive percentage
      of high HSP10 expression in astrocytoma 42/103, 40.8%) was significantly higher
      than that in the non-tumor control brain tissues (8/43, 18.6%) (P = 0.01). While
      no apparent difference of high c-PARP expression existed between astrocytoma and
      non-tumor control brain tissues. Furthermore, elevated expression of HSP10 was
      negative related to low expression of c-PARP (r = -0.224, P = 0.023), indicating
      high expression of HSP10 in astrocytoma inhibited apoptosis process effectively.
      And overexpression of HSP10 was proved to be the independent poor prognostic
      factor for astrocytoma by multivariate analysis. Taken together, our results
      suggest that elevated expression of HSP10 protein inhibits apoptosis and
      associates with poor prognosis of astrocytoma.

PMID- 29028812
TI  - Occurrence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) across
      the Gulf Corporation Council countries: Four years update.
AB  - The emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
      infections has become a global issue of dire concerns. MERS-CoV infections have
      been identified in many countries all over the world whereas high level
      occurrences have been documented in the Middle East and Korea. MERS-CoV is mainly
      spreading across the geographical region of the Middle East, especially in the
      Arabian Peninsula, while some imported sporadic cases were reported from the
      Europe, North America, Africa, and lately Asia. The prevalence of MERS-CoV
      infections across the Gulf Corporation Council (GCC) countries still remains
      unclear. Therefore, the objective of the current study was to report the
      prevalence of MERS-CoV in the GCC countries and to also elucidate on its
      demographics in the Arabian Peninsula. To date, the World Health Organization
      (WHO) has reported 1,797 laboratory-confirmed cases of MERS-CoV infection since
      June 2012, involving 687 deaths in 27 different countries worldwide. Within a
      time span of 4 years from June 2012 to July 2016, we collect samples form MERS
      CoV infected individuals from National Guard Hospital, Riyadh, and Ministry of
      health Saudi Arabia and other GCC countries. Our data comprise a total of 1550
      cases (67.1% male and 32.9% female). The age-specific prevalence and distribution
      of MERS-CoV was as follow: <20 yrs (36 cases: 3.28%), 20-39 yrs (331 cases:
      30.15%), 40-59 yrs (314 cases: 28.60%), and the highest-risk elderly group aged
      >=60 yrs (417 cases: 37.98%). The case distribution among GCC countries was as
      follows: Saudi Arabia (1441 cases: 93%), Kuwait (4 cases: 0.3%), Bahrain (1 case:
      0.1%), Oman (8 cases: 0.5%), Qatar (16 cases: 1.0%), and United Arab Emirates (80
      cases: 5.2%). Thus, MERS-CoV was found to be more prevalent in Saudi Arabia
      especially in Riyadh, where 756 cases (52.4%) were the worst hit area of the
      country identified, followed by the western region Makkah where 298 cases (20.6%)
      were recorded. This prevalence update indicates that the Arabian Peninsula,
      particularly Saudi Arabia, is the hardest hit region regarding the emerging MERS
      CoV infections worldwide. GCC countries including Saudi Arabia now have the
      infrastructure in place that allows physicians and scientific community to
      identify and immediately respond to the potential risks posed by new outbreaks of
      MERS-CoV infections in the region. Given the continuum of emergence and the large
      magnitude of the disease in our region, more studies will be required to bolster
      capabilities for timely detection and effective control and prevention of MERS
      CoV in our region.

PMID- 29028813
TI  - Evaluation of shedding, tissue burdens, and humoral immune response in goats
      after experimental challenge with the virulent Brucella melitensis strain 16M and
      the reduced virulence vaccine strain Rev. 1.
AB  - Brucella melitensis is the causative agent of brucellosis in small ruminants and
      is of considerable economic and public health importance in many countries
      worldwide. The control of disease in humans depends on the control of disease in
      livestock; however, few counties with endemic B. melitensis infection have been
      able to successfully eradicate this pathogen. This underscores the need for
      further research on the pathogenesis of both virulent and vaccine strains of B.
      melitensis in the small ruminant host. The aim of the present study was to
      characterize clinical effects, tissue colonization, shedding, and humoral immune
      response following B. melitensis infection in goats. Both virulent (16M) and
      reduced virulence (Rev. 1) strains of B. melitensis were studied. Pregnant goats
      were infected at 11-14 weeks of gestation with 8 x 106 or 8 x 107 CFU of B.
      melitensis. Infection of goats with B. melitensis 16M resulted in an 86% abortion
      rate. This strain disseminated widely in pregnant does post-infection with none
      of the 15 sampled tissues spared from colonization. Importantly, we report the
      first isolation of B. melitensis from muscle tissue in ruminants. Pathogenesis of
      Rev. 1 infection was variable with two does showing minimal colonization and one
      doe exhibiting disease similar to that of animals infected with fully virulent
      16M. Shedding of B. melitensis in milk occurred in all 16M- and Rev. 1- infected
      goats. In pregnant animals challenged with virulent B. melitensis, median time to
      seroconversion was 21 days; however, 2 animals did not seroconvert until after
      abortion.

PMID- 29028814
TI  - Diversity and microevolution of CRISPR loci in Helicobacter cinaedi.
AB  - Helicobacter cinaedi is associated with nosocomial infections. The CRISPR-Cas
      system provides adaptive immunity against foreign genetic elements. We
      investigated the CRISPR-Cas system in H. cinaedi to assess the potential of the
      CRISPR-based microevolution of H. cinaedi strains. A genotyping method based on
      CRISPR spacer organization was carried out using 42 H. cinaedi strains. The
      results of sequence analysis showed that the H. cinaedi strains used in this
      study had two CRISPR loci (CRISPR1 and CRISPR2). The lengths of the consensus
      direct repeat sequences in CRISPR1 and CRISPR2 were both 36 bp-long, and 224
      spacers were found in the 42 H. cinaedi strains. Analysis of the organization and
      sequence similarity of the spacers of the H. cinaedi strains showed that CRISPR
      arrays could be divided into 7 different genotypes. Each genotype had a different
      ancestral spacer, and spacer acquisition/deletion events occurred while isolates
      were spreading. Spacer polymorphisms of conserved arrays across the strains were
      instrumental for differentiating closely-related strains collected from the same
      hospital. MLST had little variability, while the CRISPR sequences showed
      remarkable diversity. Our data revealed the structural features of H. cinaedi
      CRISPR loci for the first time. CRISPR sequences constitute a valuable basis for
      genotyping, provide insights into the divergence and relatedness between closely
      related strains, and reflect the microevolutionary process of H. cinaedi.

PMID- 29028815
TI  - Striatal astrocytes engulf dopaminergic debris in Parkinson's disease: A study in
      an animal model.
AB  - The role of astrocytes in Parkinson's disease is still not well understood. This
      work studied the astrocytic response to the dopaminergic denervation. Rats were
      injected in the lateral ventricles with 6-hydroxydopamine (25MUg), inducing a
      dopaminergic denervation of the striatum not accompanied by non-selective tissue
      damage. The dopaminergic debris were found within spheroids (free-spheroids)
      which retained some proteins of dopaminergic neurons (e.g., tyrosine hydroxylase,
      the dopamine transporter protein, and APP) but not others (e.g., alpha
      synuclein). Free-spheroids showed the initial (LC3-autophagosomes) but not the
      late (Lamp1/Lamp2-lysosomes) components of autophagy (incomplete autophagy),
      preparing their autophagosomes for an external phagocytosis (accumulation of
      phosphatidylserine). Free-spheroids were penetrated by astrocyte processes
      (fenestrated-spheroids) which made them immunoreactive for GFAP and S100beta, and
      which had some elements needed to continue the debris degradation (Lamp1/Lamp2).
      Finally, proteins normally found in neurons (TH, DAT and alpha-synuclein) were
      observed within astrocytes 2-5 days after the dopaminergic degeneration,
      suggesting that the intracellular contents of degenerated cells had been
      transferred to astrocytes. Taken together, present data suggest phagocytosis as a
      physiological role of striatal astrocytes, a role which could be critical for
      cleaning striatal debris during the initial stages of Parkinson's disease.

PMID- 29028816
TI  - Comparison of acute kidney injury between open and laparoscopic liver resection:
      Propensity score analysis.
AB  - The inflammatory response has been shown to be a major contributor to acute
      kidney injury. Considering that laparoscopic surgery is beneficial in reducing
      the inflammatory response, we compared the incidence of postoperative acute
      kidney injury between laparoscopic liver resection and open liver resection.
      Among 1173 patients who underwent liver resection surgery, 222 of 926 patients
      who underwent open liver resection were matched with 222 of 247 patients who
      underwent laparoscopic liver resection, by using propensity score analysis. The
      incidence of postoperative acute kidney injury assessed according to the
      creatinine criteria of the Kidney Disease: Improving Global Outcomes definition
      was compared between those 1:1 matched groups. A total 77 (6.6%) cases of
      postoperative acute kidney injury occurred. Before matching, the incidence of
      acute kidney injury after laparoscopic liver resection was significantly lower
      than that after open liver resection [1.6% (4/247) vs. 7.9% (73/926), P < 0.001].
      After 1:1 matching, the incidence of postoperative acute kidney injury was still
      significantly lower after laparoscopic liver resection than after open liver
      resection [1.8% (4/222) vs. 6.3% (14/222), P = 0.008; odds ratio 0.273, 95%
      confidence interval 0.088-0.842, P = 0.024]. The postoperative inflammatory
      marker was also lower in laparoscopic liver resection than in open liver
      resection in matched set data (white blood cell count 12.7 +/- 4.0 * 103/MUL vs.
      14.9 +/- 3.9 * 103/MUL, P < 0.001). Our findings suggest that the laparoscopic
      technique, by decreasing the inflammatory response, may reduce the occurrence of
      postoperative acute kidney injury during liver resection surgery.

PMID- 29028818
TI  - Floral structure and ontogeny of Syndiclis (Lauraceae).
AB  - Generic delimitation in the Beilschmiedia group of the Lauraceae remains
      ambiguous because flowering specimens of a few genera with confined distribution
      are poorly represented in herbaria, and a few floral characters important for
      taxonomy are still poorly known. Syndiclis is sporadically distributed in
      southwestern China, and is represented in the herbaria by only a few flowering
      specimens. We conducted field investigations to collect floral materials of four
      species and observed structures and ontogeny of the tiny flowers using both light
      microscopy (LM) and scanning electron microscopy (SEM). The results show that the
      genus Syndiclis possesses flowers with huge variation in both merosity and organ
      number. Flowers of the genus are dimerous, trimerous, or tetramerous, or have
      mixed merosity with monomerous and dimerous, or dimerous and trimerous, or
      trimerous and tetramerous whorls. The number of staminodes ranges from two to
      eight, depending on floral merosity, and on how many stamens of the third
      androecial whorl are reduced to staminodes. The staminodes of the fourth
      androecial whorl are comparable to the staminodes in Potameia, but the staminodes
      of the third androecial whorl of Syndiclis are relatively larger than the
      staminodes in Potameia. They are erect or curved inwards, covering the ovary. The
      anthers are usually two-locular, but rarely one-locular or three-locular. Each
      stamen of the third androecial whorl bears two conspicuous and enlarged glands at
      the base. The lability of floral merosity and organ number of Syndiclis may have
      been caused by changes of pollination system and loss of special selective
      pressures that are present in most Lauraceous plants with fixed floral organ
      number. This study furthers our understanding of variation and evolution of a few
      important characters of the Beilschmiedia group and provides essential data for a
      revised generic classification of the group.

PMID- 29028817
TI  - Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism:
      A blinded case-control study.
AB  - Gastrointestinal (GI) symptoms are prevalent in autism spectrum disorder (ASD)
      but the pathophysiology is poorly understood. Imbalances in the enteric
      microbiome have been associated with ASD and can cause GI dysfunction potentially
      through disruption of mitochondrial function as microbiome metabolites modulate
      mitochondrial function and mitochondrial dysfunction is highly associated with GI
      symptoms. In this study, we compared mitochondrial function in rectal and cecum
      biopsies under the assumption that certain microbiome metabolites, such as
      butyrate and propionic acid, are more abundant in the cecum as compared to the
      rectum. Rectal and cecum mucosal biopsies were collected during elective
      diagnostic colonoscopy. Using a single-blind case-control design, complex I and
      IV and citrate synthase activities and complex I-V protein quantity from 10
      children with ASD, 10 children with Crohn's disease and 10 neurotypical children
      with nonspecific GI complaints were measured. The protein for all complexes,
      except complex II, in the cecum as compared to the rectum was significantly
      higher in ASD samples as compared to other groups. For both rectal and cecum
      biopsies, ASD samples demonstrated higher complex I activity, but not complex IV
      or citrate synthase activity, compared to other groups. Mitochondrial function in
      the gut mucosa from children with ASD was found to be significantly different
      than other groups who manifested similar GI symptomatology suggesting a unique
      pathophysiology for GI symptoms in children with ASD. Abnormalities localized to
      the cecum suggest a role for imbalances in the microbiome, potentially in the
      production of butyrate, in children with ASD.

PMID- 29028819
TI  - The anti-myeloma activity of bone morphogenetic protein 2 predominantly relies on
      the induction of growth arrest and is apoptosis-independent.
AB  - Multiple myeloma (MM), a malignancy of the bone marrow, is characterized by a
      pathological increase in antibody-producing plasma cells and an increase in
      immunoglobulins (plasmacytosis). In recent years, bone morphogenetic proteins
      (BMPs) have been reported to be activators of apoptotic cell death in neoplastic
      B cells in MM. Here, we use bone morphogenetic protein 2 (BMP2) to show that the
      "apoptotic" effect of BMPs on human neoplastic B cells is dominated by anti
      proliferative activities and cell cycle arrest and is apoptosis-independent. The
      anti-proliferative effect of BMP2 was analysed in the human cell lines KMS12-BM
      and L363 using WST-1 and a Coulter counter and was confirmed using CytoTox assays
      with established inhibitors of programmed cell death (zVAD-fmk and necrostatin
      1). Furthermore, apoptotic activity was compared in both cell lines employing
      western blot analysis for caspase 3 and 8 in cells treated with BMP2 and FasL.
      Additionally, expression profiles of marker genes of different cell death
      pathways were analysed in both cell lines after stimulation with BMP2 for 48h
      using an RT-PCR-based array. In our experiments we observed that there was rather
      no reduction in absolute cell number, but cells stopped proliferating following
      treatment with BMP2 instead. The time frame (48-72 h) after BMP2 treatment at
      which a reduction in cell number is detectable is too long to indicate a directly
      BMP2-triggered apoptosis. Moreover, in comparison to robust apoptosis induced by
      the approved apoptotic factor FasL, BMP2 only marginally induced cell death.
      Consistently, neither the known inhibitor of apoptotic cell death zVAD-fmk nor
      the necroptosis inhibitor necrostatin-1 was able to rescue myeloma cell growth in
      the presence of BMP2.

PMID- 29028820
TI  - A C-terminal motif contributes to the plasma membrane localization of Arabidopsis
      STP transporters.
AB  - Membrane trafficking is highly organized to maintain cellular homeostasis in any
      organisms. Membrane-embedded transporters are targeted to various organelles to
      execute appropriate partition and allocation of their substrates, such as ions or
      sugars. To ensure the fidelity of targeting and sorting, membrane proteins
      including transporters have sorting signals that specify the subcellular
      destination and the trafficking pathway by which the destination is to be
      reached. Here, we have identified a novel sorting signal (called the tri-aromatic
      motif) which contains three aromatic residues, two tryptophans and one histidine,
      for the plasma membrane localization of sugar transporters in the STP family in
      Arabidopsis. We firstly found that a C-terminal deletion disrupted the sugar
      uptake activity of STP1 in yeast cells. Additional deletion and mutation analyses
      demonstrated that the three aromatic residues in the C-terminus, conserved among
      all Arabidopsis STP transporters, were critical for sugar uptake by not only STP1
      but also another STP transporter STP13. We observed that, when the tri-aromatic
      motif was mutated, STP1 was largely localized at the endomembrane compartments in
      yeast cells, indicating that this improper subcellular localization led to the
      loss of sugar absorption. Importantly, our further analyses uncovered that
      mutations of the tri-aromatic motif resulted in the endoplasmic reticulum (ER)
      retention of STP1 and STP13 in plant cells, suggesting that this motif is
      involved at the step of ER exit of STP transporters to facilitate their plasma
      membrane localization. Together, we here identified a novel ER export signal, and
      showed that appropriate sorting via the tri-aromatic motif is important for sugar
      absorption by STP transporters.

PMID- 29028821
TI  - Load-sensitive impairment of working memory for biological motion in
      schizophrenia.
AB  - Impaired working memory (WM) is a core cognitive deficit in schizophrenia.
      Nevertheless, past studies have reported that patients may also benefit from
      increasing salience of memory stimuli. Such efficient encoding largely depends
      upon precise perception. Thus an investigation on the relationship between
      perceptual processing and WM would be worthwhile. Here, we used biological motion
      (BM), a socially relevant stimulus that schizophrenics have difficulty
      discriminating from similar meaningless motions, in a delayed-response task. Non
      BM stimuli and static polygons were also used for comparison. In each trial, one
      of the three types of stimuli was presented followed by two probes, with a short
      delay in between. Participants were asked to indicate whether one of them was
      identical to the memory item or both were novel. The number of memory items was
      one or two. Healthy controls were more accurate in recognizing BM than non-BM
      regardless of memory loads. Patients with schizophrenia exhibited similar
      accuracy patterns to those of controls in the Load 1 condition only. These
      results suggest that information contained in BM could facilitate WM encoding in
      general, but the effect is vulnerable to the increase of cognitive load in
      schizophrenia, implying inefficient encoding driven by imprecise perception.

PMID- 29028822
TI  - Serial-omics characterization of equine urine.
AB  - Horse urine is easily collected and contains molecules readily measurable using
      mass spectrometry that can be used as biomarkers representative of health,
      disease or drug tampering. This study aimed at analyzing microliter levels of
      horse urine to purify, identify and quantify proteins, polar metabolites and non
      polar lipids. Urine from a healthy 12 year old quarter horse mare on a diet of
      grass hay and vitamin/mineral supplements with limited pasture access was
      collected for serial-omics characterization. The urine was treated with methyl
      tert-butyl ether (MTBE) and methanol to partition into three distinct layers for
      protein, non-polar lipid and polar metabolite content from a single liquid-liquid
      extraction and was repeated two times. Each layer was analyzed by high
      performance liquid chromatography-high resolution tandem mass spectrometry (LC
      MS/MS) to obtain protein sequence and relative protein levels as well as identify
      and quantify small polar metabolites and lipids. The results show 46 urine
      proteins, many related to normal kidney function, structural and circulatory
      proteins as well as 474 small polar metabolites but only 10 lipid molecules.
      Metabolites were mostly related to urea cycle and ammonia recycling as well as
      amino acid related pathways, plant diet specific molecules, etc. The few lipids
      represented triglycerides and phospholipids. These data show a complete mass
      spectrometry based-omics characterization of equine urine from a single 333 MUL
      mid-stream urine aliquot. These omics data help serve as a baseline for healthy
      mare urine composition and the analyses can be used to monitor disease
      progression, health status, monitor drug use, etc.

PMID- 29028823
TI  - Novel mutations in Darier disease and association to self-reported disease
      severity.
AB  - Darier disease is a rare and severe autosomal dominant skin disease characterised
      by malodorous keratotic papules in seborrheic areas of the skin. Darier disease
      affects up to 1 in 30 000 people and is caused by mutations in the ATP2A2 gene,
      which encodes to the sarco/endoplasmic reticulum calcium-ATPase isoform 2 that
      pumps calcium into the endoplasmic reticulum. Although many ATP2A2 variants have
      been described, it is not known if genotype correlates with phenotype, which
      could be important for prognosis and treatment. This is the first study to use
      whole exome sequencing to screen the ATP2A2 gene in a cohort of 28 clinically
      diagnosed Darier disease patients. Twenty-one different disease causing variants
      were identified and 15 of these were novel. Sixteen of the 21 variants were
      predicted to be pathogenic using in silico prediction programs. There were seven
      missense, four intronic/splice-sites, three frameshifts, two in-frame deletions,
      four nonsense and one synonymous mutations. This study also found ten patients
      who harbour more than one ATP2A2 variant. The phenotype of the patient cohort was
      assessed by photography and by patient questionnaires. The genotype-phenotype
      association was examined for all variants in relation to the patient's disease
      severity score, and no correlation could be established.

PMID- 29028824
TI  - The association between serum brain-derived neurotrophic factor and a cluster of
      cardiovascular risk factors in adolescents: The CHAMPS-study DK.
AB  - BACKGROUND AND OBJECTIVE: Cardiovascular disease and type 2 diabetes pose a
      global health burden. Therefore, clarifying the pathology of these risk factors
      is essential. Previous studies have found positive and negative associations
      between one or more cardiovascular risk factors and brain-derived neurotrophic
      factor (BDNF) probably due to diverse methodological approaches when analysing
      peripheral BDNF levels. Moreover, only a few studies have been performed in youth
      populations. Consequently, the main objective of this study was to examine the
      association between serum BDNF and a composite z-score consisting of six
      cardiovascular risk factors. A secondary aim was to examine the associations
      between serum BDNF and each of the six risk factors. METHODS: Four hundred and
      forty-seven apparently healthy adolescents between 11-17 years of age
      participated in this cross-sectional study. Cardiorespiratory fitness (CRF),
      anthropometrics, pubertal status, blood pressure (BP), serum BDNF, high-density
      lipoprotein cholesterol (HDL-C), triglyceride (TG), blood glucose and insulin
      were measured. Information about alcohol consumption and socio-economic status
      was collected via questionnaires. Associations were modelled using linear
      regression analysis. RESULTS: Serum BDNF was positively associated with the
      composite z-score in the total study sample (standardized beta coefficient
      (std.beta) = 0.10, P = 0.037). In males, serum BDNF was positively associated
      with the composite z-score (Std. beta = 0.14, P = 0.034) and HOMA-IR (Std. beta =
      0.19, P = 0.004), and negatively associated with CRF (Std. beta = -0.15, P =
      0.026). In females, BDNF was positively associated with TG (Std. beta = 0.14, P =
      0.030) and negatively associated with waist circumference (WC) (Std. beta = 
      0.16, P = 0.012). CONCLUSION: Serum BDNF was positively associated with a
      composite z-score of cardiovascular risk factors. This association seems to be
      mainly driven by the association between TG, HOMA-IR and serum BDNF, and
      particularly for males. Further longitudinal research is warranted to determine
      the temporal relationship between BDNF and cardiovascular risk factors.

PMID- 29028825
TI  - Specvis: Free and open-source software for visual field examination.
AB  - Visual field impairment affects more than 100 million people globally. However,
      due to the lack of the access to appropriate ophthalmic healthcare in undeveloped
      regions as a result of associated costs and expertise this number may be an
      underestimate. Improved access to affordable diagnostic software designed for
      visual field examination could slow the progression of diseases, such as
      glaucoma, allowing for early diagnosis and intervention. We have developed
      Specvis, a free and open-source application written in Java programming language
      that can run on any personal computer to meet this requirement
      (http://www.specvis.pl/). Specvis was tested on glaucomatous, retinitis
      pigmentosa and stroke patients and the results were compared to results using the
      Medmont M700 Automated Static Perimeter. The application was also tested for
      inter-test intrapersonal variability. The results from both validation studies
      indicated low inter-test intrapersonal variability, and suitable reliability for
      a fast and simple assessment of visual field impairment. Specvis easily
      identifies visual field areas of zero sensitivity and allows for evaluation of
      its levels throughout the visual field. Thus, Specvis is a new, reliable
      application that can be successfully used for visual field examination and can
      fill the gap between confrontation and perimetry tests. The main advantages of
      Specvis over existing methods are its availability (free), affordability (runs on
      any personal computer), and reliability (comparable to high-cost solutions).

PMID- 29028828
TI  - ISED: Constructing a high-resolution elevation road dataset from massive, low
      quality in-situ observations derived from geosocial fitness tracking data.
AB  - Gaining access to inexpensive, high-resolution, up-to-date, three-dimensional
      road network data is a top priority beyond research, as such data would fuel
      applications in industry, governments, and the broader public alike. Road network
      data are openly available via user-generated content such as OpenStreetMap (OSM)
      but lack the resolution required for many tasks, e.g., emergency management. More
      importantly, however, few publicly available data offer information on elevation
      and slope. For most parts of the world, up-to-date digital elevation products
      with a resolution of less than 10 meters are a distant dream and, if available,
      those datasets have to be matched to the road network through an error-prone
      process. In this paper we present a radically different approach by deriving road
      network elevation data from massive amounts of in-situ observations extracted
      from user-contributed data from an online social fitness tracking application.
      While each individual observation may be of low-quality in terms of resolution
      and accuracy, taken together they form an accurate, high-resolution, up-to-date,
      three-dimensional road network that excels where other technologies such as LiDAR
      fail, e.g., in case of overpasses, overhangs, and so forth. In fact, the 1m
      spatial resolution dataset created in this research based on 350 million
      individual 3D location fixes has an RMSE of approximately 3.11m compared to a
      LiDAR-based ground-truth and can be used to enhance existing road network
      datasets where individual elevation fixes differ by up to 60m. In contrast, using
      interpolated data from the National Elevation Dataset (NED) results in 4.75m RMSE
      compared to the base line. We utilize Linked Data technologies to integrate the
      proposed high-resolution dataset with OpenStreetMap road geometries without
      requiring any changes to the OSM data model.

PMID- 29028826
TI  - Identification of cis-regulatory sequences reveals potential participation of
      lola and Deaf1 transcription factors in Anopheles gambiae innate immune response.
AB  - The innate immune response of Anopheles gambiae involves the transcriptional
      upregulation of effector genes. Therefore, the cis-regulatory sequences and their
      cognate binding factors play essential roles in the mosquito's immune response.
      However, the genetic control of the mosquito's innate immune response is not yet
      fully understood. To gain further insight on the elements, the factors and the
      potential mechanisms involved, an open chromatin profiling was carried out on A.
      gambiae-derived immune-responsive cells. Here, we report the identification of
      cis-regulatory sites, immunity-related transcription factor binding sites, and
      cis-regulatory modules. A de novo motif discovery carried out on this set of cis
      regulatory sequences identified immunity-related motifs and cis-regulatory
      modules. These modules contain motifs that are similar to binding sites for REL-,
      STAT-, lola- and Deaf1-type transcription factors. Sequence motifs similar to the
      binding sites for GAGA were found within a cis-regulatory module, together with
      immunity-related transcription factor binding sites. The presence of Deaf1- and
      lola-type binding sites, along with REL- and STAT-type binding sites, suggests
      that the immunity function of these two factors could have been conserved both in
      Drosophila and Anopheles gambiae.

PMID- 29028827
TI  - P. falciparum infection and maternofetal antibody transfer in malaria-endemic
      settings of varying transmission.
AB  - INTRODUCTION: During pregnancy, immunoglobulin G (IgG) is transferred from the
      mother to the fetus, providing protection from disease in early infancy.
      Plasmodium falciparum infections may reduce maternofetal antibody transfer
      efficiency, but mechanisms remain unclear. METHODS: Mother-cord paired serum
      samples collected at delivery from Papua New Guinea (PNG) and the Thailand
      Myanmar Border Area (TMBA) were tested for IgG1 and IgG3 to four P. falciparum
      antigens and measles antigen, as well as total serum IgG. Multivariable linear
      regression was conducted to assess the association of peripheral P. falciparum
      infection during pregnancy or placental P. falciparum infection assessed at
      delivery with maternofetal antibody transfer efficiency. Path analysis assessed
      the extent to which associations between P. falciparum infection and antibody
      transfer were mediated by gestational age at delivery or levels of maternal total
      serum IgG. RESULTS: Maternofetal antibody transfer efficiency of IgG1 and IgG3
      was lower in PNG compared to TMBA (mean difference in cord antibody levels
      (controlling for maternal antibody levels) ranged from -0.88 to 0.09, median of 
      0.20 log2 units). Placental P. falciparum infections were associated with
      substantially lower maternofetal antibody transfer efficiency in PNG primigravid
      women (mean difference in cord antibody levels (controlling for maternal antibody
      levels) ranged from -0.62 to -0.10, median of -0.36 log2 units), but not
      multigravid women. The lower antibody transfer efficiency amongst primigravid
      women with placental infection was only partially mediated by gestational age at
      delivery (proportion indirect effect ranged from 0% to 18%), whereas no mediation
      effects of maternal total serum IgG were observed. DISCUSSION: Primigravid women
      may be at risk of impaired maternofetal antibody transport with placental P.
      falciparum infection. Direct effects of P. falciparum on the placenta, rather
      than earlier gestational age and elevated serum IgG, are likely responsible for
      the majority of the reduction in maternofetal antibody transfer efficiency with
      placental infection.

PMID- 29028829
TI  - Sodium excretion is higher in patients with rheumatoid arthritis than in matched
      controls.
AB  - OBJECTIVE: It was shown that sodium can promote auto-immunity through the
      activation of the Th17 pathway. We aimed to compare sodium intake in patients
      with rheumatoid arthritis (RA) vs. matched controls. METHODS: This case-control
      study included 24 patients with RA at diagnosis and 24 controls matched by age,
      gender and body mass index. Sodium intake was evaluated by 24-hr urinary sodium
      excretion. RESULTS: Sodium excretion was greater for patients with early RA
      (2,849+/-1,350 vs. 2,182+/-751.7mg/day, p = 0.039) than controls. This difference
      remained significant after adjustment for smoking and the use of anti
      hypertensive and nonsteroidal anti-inflammatory drugs (p = 0.043). Patients with
      radiographic erosion at the time of diagnosis had a higher sodium excretion than
      those without (p = 0.028). CONCLUSION: Patients with early RA showed increased
      sodium excretion which may have contributed to autoimmunity.

PMID- 29028830
TI  - ER stress and subsequent activated calpain play a pivotal role in skeletal muscle
      wasting after severe burn injury.
AB  - Severe burns are typically followed by hypermetabolism characterized by
      significant muscle wasting, which causes considerable morbidity and mortality.
      The aim of the present study was to explore the underlying mechanisms of skeletal
      muscle damage/wasting post-burn. Rats were randomized to the sham, sham+4
      phenylbutyrate (4-PBA, a pharmacological chaperone promoting endoplasmic
      reticulum (ER) folding/trafficking, commonly considered as an inhibitor of ER),
      burn (30% total body surface area), and burn+4-PBA groups; and sacrificed at 1,
      4, 7, 14 days after the burn injury. Tibial anterior muscle was harvested for
      transmission electron microscopy, calcium imaging, gene expression and protein
      analysis of ER stress / ubiquitin-proteasome system / autophagy, and calpain
      activity measurement. The results showed that ER stress markers were increased in
      the burn group compared with the sham group, especially at post-burn days 4 and
      7, which might consequently elevate cytoplasmic calcium concentration, promote
      calpain production as well as activation, and cause skeletal muscle
      damage/wasting of TA muscle after severe burn injury. Interestingly, treatment
      with 4-PBA prevented burn-induced ER swelling and altered protein expression of
      ER stress markers and calcium release, attenuating calpain activation and
      skeletal muscle damage/wasting after severe burn injury. Atrogin-1 and LC3-II/LC3
      I ratio were also increased in the burn group compared with the sham group, while
      MuRF-1 remained unchanged; 4-PBA decreased atrogin-1 in the burn group. Taken
      together, these findings suggested that severe burn injury induces ER stress,
      which in turns causes calpain activation. ER stress and subsequent activated
      calpain play a critical role in skeletal muscle damage/wasting in burned rats.

PMID- 29028832
TI  - Correction: Use of the 22C3 anti-PD-L1 antibody to determine PD-L1 expression in
      multiple automated immunohistochemistry platforms.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0183023.].

PMID- 29028831
TI  - Short-term vitamin E treatment impairs reactive oxygen species signaling required
      for adipose tissue expansion, resulting in fatty liver and insulin resistance in
      obese mice.
AB  - OBJECTIVES: The use of antioxidant therapy in the treatment of oxidative stress
      related diseases such as cardiovascular disease, diabetes or obesity remains
      controversial. Our aim is to demonstrate that antioxidant supplementation may
      promote negative effects if used before the establishment of oxidative stress due
      to a reduced ROS generation under physiological levels, in a mice model of
      obesity. METHODS: C57BL/6J mice were fed with a high-fat diet for 14 weeks, with
      (OE group) or without (O group) vitamin E supplementation. RESULTS: O mice
      developed a mild degree of obesity, which was not enough to induce metabolic
      alterations or oxidative stress. These animals exhibited a healthy expansion of
      retroperitoneal white adipose tissue (rpWAT) and the liver showed no signs of
      lipotoxicity. Interestingly, despite achieving a similar body weight, OE mice
      were insulin resistant. In the rpWAT they presented a reduced generation of ROS,
      even below physiological levels (C: 1651.0 +/- 212.0; O: 3113 +/- 284.7; OE:
      917.6 +/-104.4 RFU/mg protein. C vs OE p< 0.01). ROS decay may impair their
      action as second messengers, which could account for the reduced adipocyte
      differentiation, lipid transport and adipogenesis compared to the O group.
      Together, these processes limited the expansion of this fat pad and as a
      consequence, lipid flux shifted towards the liver, causing steatosis and
      hepatomegaly, which may contribute to the marked insulin resistance. CONCLUSIONS:
      This study provides in vivo evidence for the role of ROS as second messengers in
      adipogenesis, lipid metabolism and insulin signaling. Reducing ROS generation
      below physiological levels when the oxidative process has not yet been
      established may be the cause of the controversial results obtained by antioxidant
      therapy.

PMID- 29028834
TI  - Validation of a theoretically motivated approach to measuring childhood
      socioeconomic circumstances in the Health and Retirement Study.
AB  - Childhood socioeconomic status (cSES) is a powerful predictor of adult health,
      but its operationalization and measurement varies across studies. Using Health
      and Retirement Study data (HRS, which is nationally representative of community
      residing United States adults aged 50+ years), we specified theoretically
      motivated cSES measures, evaluated their reliability and validity, and compared
      their performance to other cSES indices. HRS respondent data (N = 31,169,
      interviewed 1992-2010) were used to construct a cSES index reflecting childhood
      social capital (cSC), childhood financial capital (cFC), and childhood human
      capital (cHC), using retrospective reports from when the respondent was <16 years
      (at least 34 years prior). We assessed internal consistency reliability
      (Cronbach's alpha) for the scales (cSC and cFC), and construct validity, and
      predictive validity for all measures. Validity was assessed with hypothesized
      correlates of cSES (educational attainment, measured adult height, self-reported
      childhood health, childhood learning problems, childhood drug and alcohol
      problems). We then compared the performance of our validated measures with other
      indices used in HRS in predicting self-rated health and number of depressive
      symptoms, measured in 2010. Internal consistency reliability was acceptable (cSC
      = 0.63, cFC = 0.61). Most measures were associated with hypothesized correlates
      (for example, the association between educational attainment and cSC was 0.01, p
      < 0.0001), with the exception that measured height was not associated with cFC (p
      = 0.19) and childhood drug and alcohol problems (p = 0.41), and childhood
      learning problems (p = 0.12) were not associated with cHC. Our measures explained
      slightly more variability in self-rated health (adjusted R2 = 0.07 vs. <0.06) and
      number of depressive symptoms (adjusted R2 > 0.05 vs. < 0.04) than alternative
      indices. Our cSES measures use latent variable models to handle item-missingness,
      thereby increasing the sample size available for analysis compared to complete
      case approaches (N = 15,345 vs. 8,248). Adopting this type of theoretically
      motivated operationalization of cSES may strengthen the quality of research on
      the effects of cSES on health outcomes.

PMID- 29028833
TI  - Merkel cell polyomavirus recruits MYCL to the EP400 complex to promote
      oncogenesis.
AB  - Merkel cell carcinoma (MCC) frequently contains integrated copies of Merkel cell
      polyomavirus DNA that express a truncated form of Large T antigen (LT) and an
      intact Small T antigen (ST). While LT binds RB and inactivates its tumor
      suppressor function, it is less clear how ST contributes to MCC tumorigenesis.
      Here we show that ST binds specifically to the MYC homolog MYCL (L-MYC) and
      recruits it to the 15-component EP400 histone acetyltransferase and chromatin
      remodeling complex. We performed a large-scale immunoprecipitation for ST and
      identified co-precipitating proteins by mass spectrometry. In addition to protein
      phosphatase 2A (PP2A) subunits, we identified MYCL and its heterodimeric partner
      MAX plus the EP400 complex. Immunoprecipitation for MAX and EP400 complex
      components confirmed their association with ST. We determined that the ST-MYCL
      EP400 complex binds together to specific gene promoters and activates their
      expression by integrating chromatin immunoprecipitation with sequencing (ChIP
      seq) and RNA-seq. MYCL and EP400 were required for maintenance of cell viability
      and cooperated with ST to promote gene expression in MCC cell lines. A genome
      wide CRISPR-Cas9 screen confirmed the requirement for MYCL and EP400 in MCPyV
      positive MCC cell lines. We demonstrate that ST can activate gene expression in a
      EP400 and MYCL dependent manner and this activity contributes to cellular
      transformation and generation of induced pluripotent stem cells.

PMID- 29028835
TI  - Hydrogen peroxide yields mechanistic insights into human mRNA capping enzyme
      function.
AB  - Capping of nascent RNA polymerase II (Pol II) transcripts is required for gene
      expression and the first two steps are catalyzed by separate 5' triphosphatase
      and guanylyltransferase activities of the human capping enzyme (HCE). The cap is
      added co-transcriptionally, but how the two activities are coordinated is
      unclear. Our previous in vitro work has suggested that an unidentified factor
      modulates the minimum length at which nascent transcripts can be capped. Using
      the same well-established in vitro system with hydrogen peroxide as a capping
      inhibitor, we show that this unidentified factor targets the guanylyltransferase
      activity of HCE. We also uncover the mechanism of HCE inhibition by hydrogen
      peroxide, and by using mass spectrometry demonstrate that the active site
      cysteine residue of the HCE triphosphatase domain becomes oxidized. Using
      recombinant proteins for the two separated HCE domains, we provide evidence that
      the triphosphatase normally acts on transcripts shorter than can be acted upon by
      the guanylyltransferase. Our further characterization of the capping reaction
      dependence on transcript length and its interaction with the unidentified
      modulator of capping raises the interesting possibility that the capping reaction
      could be regulated.

PMID- 29028836
TI  - Affected pathways and transcriptional regulators in gene expression response to
      an ultra-marathon trail: Global and independent activity approaches.
AB  - Gene expression (GE) analyses on blood samples from marathon and half-marathon
      runners have reported significant impacts on the immune and inflammatory systems.
      An ultra-marathon trail (UMT) represents a greater effort due to its more testing
      conditions. For the first time, we report the genome-wide GE profiling in a group
      of 16 runners participating in an 82 km UMT competition. We quantified their
      differential GE profile before and after the race using HuGene2.0st microarrays
      (Affymetrix Inc., California, US). The results obtained were decomposed by means
      of an independent component analysis (ICA) targeting independent expression
      modes. We observed significant differences in the expression levels of 5,084
      protein coding genes resulting in an overrepresentation of 14% of the human
      biological pathways from the Kyoto Encyclopedia of Genes and Genomes database.
      These were mainly clustered on terms related with protein synthesis repression,
      altered immune system and infectious diseases related mechanisms. In a second
      analysis, 27 out of the 196 transcriptional regulators (TRs) included in the Open
      Regulatory Annotation database were overrepresented. Among these TRs, we
      identified transcription factors from the hypoxia-inducible factors (HIF) family
      EPAS1 (p< 0.01) and HIF1A (p<0.001), and others jointly described in the
      gluconeogenesis program such as HNF4 (p< 0.001), EGR1 (p<0.001), CEBPA (p< 0.001)
      and a highly specific TR, YY1 (p<0.01). The five independent components, obtained
      from ICA, further revealed a down-regulation of 10 genes distributed in the
      complex I, III and V from the electron transport chain. This mitochondrial
      activity reduction is compatible with HIF-1 system activation. The vascular
      endothelial growth factor (VEGF) pathway, known to be regulated by HIF, also
      emerged (p<0.05). Additionally, and related to the brain rewarding circuit, the
      endocannabinoid signalling pathway was overrepresented (p<0.05).

PMID- 29028837
TI  - A pilot study for robot appearance preferences among high-functioning individuals
      with autism spectrum disorder: Implications for therapeutic use.
AB  - Recent rapid technological advances have enabled robots to fulfill a variety of
      human-like functions, leading researchers to propose the use of such technology
      for the development and subsequent validation of interventions for individuals
      with autism spectrum disorder (ASD). Although a variety of robots have been
      proposed as possible therapeutic tools, the physical appearances of humanoid
      robots currently used in therapy with these patients are highly varied. Very
      little is known about how these varied designs are experienced by individuals
      with ASD. In this study, we systematically evaluated preferences regarding robot
      appearance in a group of 16 individuals with ASD (ages 10-17). Our data suggest
      that there may be important differences in preference for different types of
      robots that vary according to interaction type for individuals with ASD.
      Specifically, within our pilot sample, children with higher-levels of reported
      ASD symptomatology reported a preference for specific humanoid robots to those
      perceived as more mechanical or mascot-like. The findings of this pilot study
      suggest that preferences and reactions to robotic interactions may vary
      tremendously across individuals with ASD. Future work should evaluate how such
      differences may be systematically measured and potentially harnessed to
      facilitate meaningful interactive and intervention paradigms.

PMID- 29028838
TI  - Sequentially optimized reconstruction strategy: A meta-strategy for perimetry
      testing.
AB  - Perimetry testing is an automated method to measure visual function and is
      heavily used for diagnosing ophthalmic and neurological conditions. Its working
      principle is to sequentially query a subject about perceived light using
      different brightness levels at different visual field locations. At a given
      location, this query-patient-feedback process is expected to converge at a
      perceived sensitivity, such that a shown stimulus intensity is observed and
      reported 50% of the time. Given this inherently time-intensive and noisy process,
      fast testing strategies are necessary in order to measure existing regions more
      effectively and reliably. In this work, we present a novel meta-strategy which
      relies on the correlative nature of visual field locations in order to strongly
      reduce the necessary number of locations that need to be examined. To do this, we
      sequentially determine locations that most effectively reduce visual field
      estimation errors in an initial training phase. We then exploit these locations
      at examination time and show that our approach can easily be combined with
      existing perceived sensitivity estimation schemes to speed up the examinations.
      Compared to state-of-the-art strategies, our approach shows marked performance
      gains with a better accuracy-speed trade-off regime for both mixed and sub
      populations.

PMID- 29028839
TI  - Interaction of the Human Respiratory Syncytial Virus matrix protein with cellular
      adaptor protein complex 3 plays a critical role in trafficking.
AB  - Human Respiratory Syncytial Virus (HRSV) is a leading cause of bronchopneumonia
      in infants and the elderly. To date, knowledge of viral and host protein
      interactions within HRSV is limited and are critical areas of research. Here, we
      show that HRSV Matrix (M) protein interacts with the cellular adaptor protein
      complex 3 specifically via its medium subunit (AP-3Mu3A). This novel protein
      protein interaction was first detected via yeast-two hybrid screen and was
      further confirmed in a mammalian system by immunofluorescence colocalization and
      co-immunoprecipitation. This novel interaction is further substantiated by the
      presence of a known tyrosine-based adaptor protein MU subunit sorting signal
      sequence, YXXF: where F is a bulky hydrophobic residue, which is conserved across
      the related RSV M proteins. Analysis of point-mutated HRSV M derivatives
      indicated that AP-3Mu3A- mediated trafficking is contingent on the presence of
      the tyrosine residue within the YXXL sorting sequence at amino acids 197-200 of
      the M protein. AP-3Mu3A is up regulated at 24 hours post-infection in infected
      cells versus mock-infected HEp2 cells. Together, our data suggests that the AP-3
      complex plays a critical role in the trafficking of HRSV proteins specifically
      matrix in epithelial cells. The results of this study add new insights and
      targets that may lead to the development of potential antivirals and attenuating
      mutations suitable for candidate vaccines in the future.

PMID- 29028840
TI  - Polymorphism of keratin 1 associates with systemic lupus erythematosus and
      systemic sclerosis in a south Chinese population.
AB  - Both systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) diseases are
      related to the genetic and environmental factors, causing damage to the skin. The
      mutations of keratin 1 gene (KRT1) were reported to associate with skin diseases.
      The single-nucleotide polymorphism (SNP, rs14024) and the indel polymorphism (cds
      indel, rs267607656), consisting mostly of the common haplotypes and could be used
      for genotyping of KRT1. We used the PCR with sequence specific primers (PCR-SSP)
      to determine the genotype of KRT1 in 164 SLE, 99 SSc patients, and 418 healthy
      controls. The results showed that the mutant with G at SNP rs14024 was associated
      with the high risk to SLE (p = 6.48*10-5) and SSc (p = 8.75*10-5), while the
      deletion allele at rs267607656 was associated with the low risk to SSc (p =
      4.89*10-4) comparing to the normal controls. Haplogenotype, Del-/MU+ was
      associated with high susceptibility to SLE (OR = 1.87, p = 0.001) and SSc (OR =
      2.29, p = 2.34*10-4). In contrast, the Haplogenotype Del+/MU- was associated with
      resistance to SLE (OR = 0.35, p = 6.24*10-5) and SSc (OR = 0.34, p = 0.001). This
      study demonstrates that the variations in KRT1 and the specific polymorphism of
      KRT1 in this Chinese Han population are associated with autoimmune diseases SLE
      and SSc. Typing KRT1 might be helpful to identify SLE and SSc patients.

PMID- 29028841
TI  - Efficacies of prevention and control measures applied during an outbreak in
      Southwest Madrid, Spain.
AB  - Leishmaniasis is a vector-borne disease of worldwide distribution, currently
      present in 98 countries. Since late 2010, an unusual increase of human visceral
      and cutaneous leishmaniasis cases has been observed in the south-western Madrid
      region, totaling more than 600 cases until 2015. Some hosts, such as human,
      domestic dog and cat, rabbit (Oryctolagus cuniculus), and hare (Lepus
      granatensis), were found infected by the parasite of this disease in the area.
      Hares were described as the most important reservoir due to their higher
      prevalence, capacity to infect the vector, and presence of the same strains as in
      humans. Various measures were adopted to prevent and control the disease, and
      since 2013 there was a slight decline in the human sickness. We used a
      mathematical model to evaluate the efficacy of each measure in reducing the
      number of infected hosts. We identified in the present model that culling both
      hares and rabbits, without immediate reposition of the animals, was the best
      measure adopted, decreasing the proportion of all infected hosts. Particularly,
      culling hares was more efficacious than culling rabbits to reduce the proportion
      of infected individuals of all hosts. Likewise, lowering vector contact with
      hares highly influenced the reduction of the proportion of infected hosts. The
      reduction of the vector density per host in the park decreased the leishmaniasis
      incidence of hosts in the park and the urban areas. On the other hand, the
      reduction of the vector density per host of the urban area (humans, dogs and
      cats) decreased only their affected population, albeit at a higher proportion.
      The use of insecticide-impregnated collar and vaccination in dogs affected only
      the infected dogs' population. The parameters related to the vector contact with
      dog, cat or human do not present a high impact on the other hosts infected by
      Leishmania. In conclusion, the efficacy of each control strategy was determined,
      in order to direct future actions in this and in other similar outbreaks. The
      present mathematical model was able to reproduce the leishmaniasis dynamics in
      the Madrid outbreak, providing theoretical support based on successful
      experiences, such as the reduction of human cases in Southwest Madrid, Spain.

PMID- 29028843
TI  - Efficiency of different air filter types for pig facilities at laboratory scale.
AB  - Air filtration has been shown to be efficient in reducing pathogen burden in
      circulating air. We determined at laboratory scale the retention efficiency of
      different air filter types either composed of a prefilter (EU class G4) and a
      secondary fiberglass filter (EU class F9) or consisting of a filter mat (EU class
      M6 and F8-9). Four filter prototypes were tested for their capability to remove
      aerosol containing equine arteritis virus (EAV), porcine reproductive and
      respiratory syndrome virus (PRRSV), bovine enterovirus 1 (BEV), Actinobacillus
      pleuropneumoniae (APP), and Staphylococcus (S.) aureus from air. Depending on the
      filter prototype and utilisation, the airflow was set at 1,800 m3/h (combination
      of upstream prefilter and fiberglass filter) or 80 m3/h (filter mat). The
      pathogens were aerosolized and their concentration was determined in front of and
      behind the filter by culture or quantitative real-time RT-PCR. Furthermore,
      survival of the pathogens over time in the filter material was determined.
      Bacteria were most efficiently filtered with a reduction rate of up to 99.9%
      depending on the filter used. An approximately 98% reduction was achieved for the
      viruses tested. Viability or infectivity of APP or PRRSV in the filter material
      decreased below the detection limit after 4 h and 24 h, respectively, whereas S.
      aureus was still culturable after 4 weeks. Our results demonstrate that pathogens
      can efficiently be reduced by air filtration. Consequently, air filtration
      combined with other strict biosecurity measures markedly reduces the risk of
      introducing airborne transmitted pathogens to animal facilities. In addition, air
      filtration might be useful in reducing bioaerosols within a pig barn, hence
      improving respiratory health of pigs.

PMID- 29028842
TI  - In vitro investigation of head and neck cancer stem cell proportions and their
      changes following X-ray irradiation as a function of HPV status.
AB  - INTRODUCTION: Some head and neck squamous cell carcinomas (HNSCC) have a distinct
      aetiology, which depends on the presence of oncogenic human papilloma virus
      (HPV). Also, HNSCC contains cancer stem cells (CSCs) that have greater
      radioresistance and capacity to change replication dynamics in response to
      irradiation compared to non-clonogenic cells. Since there is limited data on CSCs
      in HNSCC as a function of HPV status, better understanding of their radiobiology
      may enable improved treatment outcome. METHODS: Baseline and post-irradiation
      changes in CSC proportions were investigated by flow cytometry in a HPV-negative
      (UM-SCC-1) and a HPV-positive (UM-SCC-47) HNSCC cell line, using fluorescent
      staining with CD44/ALDH markers. CSC proportions in both irradiated and
      unirradiated cultures were compared for the two cell lines at various times post
      irradiation. To assess repopulation of CSCs, untreated cultures were depleted of
      CD44+/ALDH+ cells and re-cultured for 3 weeks before flow cytometry analysis.
      RESULTS: CSC proportions in untreated cell lines were 0.57% (UM-SCC-1) and 2.87%
      (UM-SCC-47). Untreated cell lines depleted of CD44+/ALDH+ repopulated this
      phenotype to a mean of 0.15% (UM-SCC-1) and 6.76% (UM-SCC-47). All UM-SCC-47
      generations showed elevated CSC proportions after irradiation, with the most
      significant increase at 2 days post-irradiation. The highest elevation in UM-SCC
      1 CSCs was observed at 1 day post-irradiation in the 2nd generation and at 3 days
      after irradiation in the 3rd generation. When measured after 10 days, only the
      3rd generation of UM-SCC-1 showed elevated CSCs. CONCLUSIONS: CSC proportions in
      both cell lines were elevated after exposure and varied with time post
      irradiation. UM-SCC-47 displayed significant plasticity in repopulating the CSC
      phenotype in depleted cultures, which was not seen in UM-SCC-1.

PMID- 29028844
TI  - A polyphenol-enriched diet and Ascaris suum infection modulate mucosal immune
      responses and gut microbiota composition in pigs.
AB  - Polyphenols are a class of bioactive plant secondary metabolites that are thought
      to have beneficial effects on gut health, such as modulation of mucosal immune
      and inflammatory responses and regulation of parasite burdens. Here, we examined
      the interactions between a polyphenol-rich diet supplement and infection with the
      enteric nematode Ascaris suum in pigs. Pigs were fed either a basal diet or the
      same diet supplemented with grape pomace (GP), an industrial by-product rich in
      polyphenols such as oligomeric proanthocyanidins. Half of the animals in each
      group were then inoculated with A. suum for 14 days to assess parasite
      establishment, acquisition of local and systemic immune responses and effects on
      the gut microbiome. Despite in vitro anthelmintic activity of GP-extracts,
      numbers of parasite larvae in the intestine were not altered by GP
      supplementation. However, the bioactive diet significantly increased numbers of
      eosinophils induced by A. suum infection in the duodenum, jejunum and ileum, and
      modulated gene expression in the jejunal mucosa of infected pigs. Both GP
      supplementation and A. suum infection induced significant and apparently similar
      changes in the composition of the prokaryotic gut microbiota, and both also
      decreased concentrations of isobutyric and isovaleric acid (branched-chain short
      chain fatty acids) in the colon. Our results demonstrate that while a polyphenol
      enriched diet in pigs may not directly influence A. suum establishment, it
      significantly modulates the subsequent host response to helminth infection. Our
      results suggest an influence of diet on immune function which may potentially be
      exploited to enhance immunity to helminths.

PMID- 29028846
TI  - Periodontal Indices and Status in 34 Growing Patients with Unilateral Cleft Lip
      and Palate: A Split-Mouth Study.
AB  - Periodontal examination in growing patients with unilateral cleft lip and palate
      was performed in a split-mouth study design. Higher plaque acumulation and
      bleeding indices were recorded for teeth on the cleft side. Pocket probing depth
      (PPD) and clinical attachment level (CAL) values were higher at lateral incisors
      and canines adjacent to the cleft. Keratinized gingiva and depth of the vestibule
      were lower adjacent to the cleft. This study shows that growing patients with
      clefts present differences regarding periodontal parameters between the cleft and
      the control side. These alterations affected patients' ability to maintain proper
      oral hygiene and resulted in differences in PPD and CAL.

PMID- 29028847
TI  - Is History of Periodontitis a Risk Factor for Peri-implant Disease? A Pilot
      Study.
AB  - PURPOSE: The aim of this pilot study was to evaluate clinical outcomes of implant
      treatment in periodontally compromised patients. MATERIALS AND METHODS: Partially
      edentulous patients who were diagnosed and treated for chronic periodontitis and
      later rehabilitated with implant-supported single crowns or fixed partial
      dentures were enrolled in this study. At the final follow-up, data on probing
      pocket depth and bleeding on probing were collected, and changes in peri-implant
      bone levels were assessed on periapical radiographs. Accordingly, patients were
      categorized into peri-implant disease-free (PID-free), peri-implant mucositis
      (PIM), or peri-implantitis (PI) groups. Additionally, information on the history
      of systemic diseases was obtained and correlated with the findings. RESULTS:
      Seven females and six males with a mean age of 55.2 (standard deviation [SD] +/-
      8.38) years were included in this study. Fifty-five implants were placed in 13
      partially edentulous patients with a history of chronic periodontitis. The mean
      follow-up in the study was 35.1 (SD +/- 2.40) months. No implants were lost in
      the 13 patients, for a cumulative survival of 100%. PI was confirmed in 3
      patients and PIM in 8 patients, while 2 patients were found to be PID-free.
      Diabetes and hypertension were found to be the predominant systemic factors among
      patients affected by peri-implant diseases. CONCLUSION: Patients with a history
      of periodontitis are at considerable risk of being affected by peri-implant
      mucositis, if not by peri-implantitis.

PMID- 29028848
TI  - The Stability of Augmented Bone Between Two Different Membranes Used for Guided
      Bone Regeneration Simultaneous with Dental Implant Placement in the Esthetic
      Zone.
AB  - PURPOSE: This randomized controlled clinical trial compared the stability of
      augmented bone between a synthetic resorbable membrane and a collagen resorbable
      membrane with guided bone regeneration (GBR) simultaneous with dental implant
      placement in the esthetic zone in terms of facial bone thickness. MATERIALS AND
      METHODS: A total of 60 dental implants from patients requiring implant placement
      with simultaneous GBR in the esthetic zone were equally allocated to the test
      group or control group by block randomization. Biphasic calcium phosphate ceramic
      bone was used in combination with either a polylactic acid (PLA) membrane (test
      group, 30 implants) or a resorbable collagen membrane (control group, 30
      implants). Cone beam computed tomographic (CBCT) images were used to assess the
      facial bone thickness postimplantation and then 6 months later at four levels:
      implant platform and 2 mm, 4 mm, and 6 mm apical to the implant shoulder.
      RESULTS: All implants were osseointegrated, and no implant loss was found during
      this study. Facial bone was detected in all cases; however, the thickness of the
      facial bone was reduced at the 6-month follow-up in both groups. The percentage
      of facial bone thickness reduction was 34.30%, 27.94%, 24.25%, and 19.81% in the
      test group and 34.80%, 24.06%, 19.52%, and 20.45% in the control group at the
      level of the implant platform and at 2 mm, 4 mm, and 6 mm apical to the implant
      shoulder, respectively. Nevertheless, there was no statistically significant
      difference between the groups (P > .05). CONCLUSION: A synthetic resorbable
      membrane revealed an amount of stable augmented bone similar to that of a
      collagen resorbable membrane.

PMID- 29028849
TI  - The Effect of Resin Cement Type and Thermomechanical Aging on the Retentive
      Strength of Custom Zirconia Abutments Bonded to Titanium Inserts.
AB  - PURPOSE: The purpose of this study was to investigate the effect of resin cement
      type on the retentive strength of custom zirconia abutments bonded to titanium
      inserts. MATERIALS AND METHODS: Sixty implant (4.3 mm diameter and 11.5 mm
      length) and custom zirconia abutment (15 mm height and 2 mm wall thickness) pairs
      were used to form six groups (n = 10 each). Three different resin cements were
      used to bond the zirconia abutments and titanium inserts: Panavia F 2.0,
      Zirconite, and Multilink Hybrid Abutment. Control groups and thermomechanically
      aged groups were formed. Specimens were subjected to tensile test to failure, and
      the retention values were analyzed by two-way analysis of variance (ANOVA).
      RESULTS: Two-way ANOVA showed a significant effect of the cement type and
      thermomechanical aging (P < .05). Regardless of the cement, control groups showed
      significantly (P < .05) higher retentive strength than the thermomechanically
      aged groups. Comparing the resin cements, the retentive strength of Zirconite,
      aged or not, was higher than that of Panavia F 2.0 and Multilink Hybrid Abutment;
      no significant differences between the latter two cements were found. In the
      Zirconite group, adhesive failure occurred mostly between the titanium and the
      resin cement. In the Panavia F 2.0 and Multilink Hybrid Abutment groups, adhesive
      failure between the zirconia and the resin cement was observed. CONCLUSION: Resin
      cement type had an effect on the retentive strength of custom zirconia abutments
      bonded to titanium inserts. Thermomechanical aging had a negative effect on the
      retentive strength. Zirconite adhesively bonded to the zirconia surface of the
      custom abutment. Differences were noted in adhesive failure types among the
      cements.

PMID- 29028845
TI  - Analysis of cell cycle parameters during the transition from unhindered growth to
      ribosomal and translational stress conditions.
AB  - Abrogation of ribosome synthesis (ribosomal stress) leads to cell cycle arrest.
      However, the immediate cell response to cessation of ribosome formation and the
      transition from normal cell proliferation to cell cycle arrest have not been
      characterized. Furthermore, there are conflicting conclusions about whether cells
      are arrested in G2/M or G1, and whether the cause is dismantling ribosomal
      assembly per se, or the ensuing decreased number of translating ribosomes. To
      address these questions, we have compared the time kinetics of key cell cycle
      parameters after inhibiting ribosome formation or function in Saccharomyces
      cerevisiae. Within one-to-two hours of repressing genes for individual ribosomal
      proteins or Translation Elongation factor 3, configurations of spindles, spindle
      pole bodies began changing. Actin began depolarizing within 4 hours. Thus the
      loss of ribosome formation and function is sensed immediately. After several
      hours no spindles or mitotic actin rings were visible, but membrane ingression
      was completed in most cells and Ace2 was localized to daughter cell nuclei
      demonstrating that the G1 stage was reached. Thus cell division was completed
      without the help of a contractile actin ring. Moreover, cell wall material held
      mother and daughter cells together resulting in delayed cell separation,
      suggesting that expression or function of daughter gluconases and chitinases is
      inhibited. Moreover, cell development changes in very similar ways in response to
      inhibition of ribosome formation and function, compatible with the notion that
      decreased translation capacity contributes to arresting the cell cycle after
      abrogation of ribosome biogenesis. Potential implications for the mechanisms of
      diseases caused by mutations in ribosomal genes (ribosomopathies) are discussed.

PMID- 29028850
TI  - Effect of Different Degrees of Mesial Implant Inclination on the Retention and
      Stability of Two-Implant Mandibular Overdentures Retained with Stud Attachments:
      An In Vitro Study.
AB  - PURPOSE: To evaluate the effect of different degrees of mesial implant
      inclinations on the retention and stability of two-implant mandibular
      overdentures retained with stud attachments. MATERIALS AND METHODS: Four
      experimental mandibular acrylic models were constructed. Two laboratory implants
      were inserted in the canine areas of each model with the following degrees of
      mesial inclinations: 0, 5, 10, and 20 degrees. Experimental overdentures were
      connected to the implants with Locator extra-light retention (Le), Locator light
      retention (Ll), and Locator medium retention (Lm). Vertical (retention) and
      oblique (stability) dislodging forces (anterior, posterior, and lateral) were
      measured at the beginning of the study (initial retention) and after 540 cycles
      of denture insertion and removal (final retention). RESULTS: The final retention
      was not significantly affected by small (5 degrees) and large (20 degrees)
      implant inclinations, but decreased with a moderate (10 degrees) inclination. For
      a small implant inclination (5 degrees), Lm showed the highest final
      retention/stability and Le showed the lowest, while for moderate and large
      inclinations (10 and 20 degrees), Le showed the highest final retention/stability
      and Lm showed the lowest. Vertical dislodging recorded the highest final
      stability, and lateral dislodgment recorded the lowest stability. CONCLUSION:
      Within the limitations of this in vitro study, only moderate implant angulation
      (10 degrees) negatively affects the final retention and stability of Locator
      retained overdentures. Locator medium retention for small angulation (5 degrees)
      and Locator extra-light retention for moderate (10 degrees) and large (20
      degrees) angulations are recommended to maintain high retention and stability
      after 540 cycles of denture insertion and removal.

PMID- 29028851
TI  - Peri-implant Crestal Bone Changes Around Zirconia Implants in Periodontally
      Healthy and Compromised Patients.
AB  - PURPOSE: No consensus regarding the efficacy of zirconia implants in maintaining
      peri-implant hard and soft tissue health has yet been obtained. The aim of this
      retrospective follow-up study was to gain knowledge about peri-implant bone
      behavior and about implant survival and success after treatment with zirconia
      dental implants in patients with normal and compromised soft and hard tissue
      conditions. MATERIALS AND METHODS: This follow-up study involved 86 patients with
      123 zirconia implants (Straumann PURE Ceramic Implant) that were radiographically
      investigated directly after implant placement (day 0), 3 months after placement,
      and 1 year after the definitive implant crown placement. The clinical assessment
      was done at the 1-year postloading appointment and also included the modified
      Plaque Index, modified Sulcus Bleeding Index, and sulcus pocket depths. Eighteen
      patients with periodontally compromised conditions were compared to 68 patients
      with healthy periodontal conditions. RESULTS: The survival rate was 100% and
      success rate was 94.5%, with no differences between the two groups. The alveolar
      crest around the ceramic implants showed no significant difference between day 0
      and 1 year postloading for both groups (P > .05). There was also no significant
      difference at 1 year postloading between the groups in the distance from the
      implant shoulder to the peri-implant bone crest (P = .67) or in pocket depth (P =
      .07). CONCLUSION: No significant peri-implant bone loss was observed in the first
      year. The survival and success rates showed no differences between the
      periodontally healthy and periodontally compromised groups; however, only a
      limited number of patients with periodontally compromised conditions were
      included in this study.

PMID- 29028852
TI  - Biocompatibility and Osseointegration of Titanium Implants with a Silver-Doped
      Polysiloxane Coating: An In Vivo Pig Model.
AB  - PURPOSE: To test the antimicrobial properties, surface topography, reaction of
      surrounding tissue (biocompatibility), and osseointegration of ultrathin implant
      surfaces containing polysiloxane and nanoscaled silver particles. MATERIALS AND
      METHODS: Implants with polysiloxane coating and nanoscaled silver particles
      (Ag/SiOxCy; HyProtect, Bio-Gate) were compared with implants with polysiloxane
      coating alone and with noncoated (grit-blasted and acid-etched) implants. A total
      of 72 implants were inserted into the calvaria of eight domestic pigs (nine
      implants each, three of each type). After 3 months, histologic sections were
      evaluated for inflammatory cell infiltration and bone implant contact. RESULTS:
      Roughness parameters did not differ between all three implant types. The
      Ag/SiOxCy coating exhibited a good antimicrobial effect in vitro and no sign of
      inflammatory cell infiltration in vivo. The noncoated implants demonstrated
      10.85% and 14.48% more bone contact than the polysiloxane-coated implants (P =
      .003) and the Ag/SiOxCy-coated implants (P <= .001), respectively.
      Osseointegration was not significantly different between the Ag/SiOxCy-coated and
      polysiloxane-coated implants (P = .72). CONCLUSION: The osseointegration
      capability of the Ag/SiOxCy-coated implants was equal to that of the polysiloxane
      coated implants but less than that of the grit-blasted and acid-etched implants.
      Because of the biocompatibility of the polysiloxane coating, further studies
      should be conducted in load-bearing models and in the oral cavity to investigate
      the antimicrobial effect of the embedded silver clusters.

PMID- 29028853
TI  - Impact of Sex, Age, and Season on Sinus Membrane Thickness.
AB  - PURPOSE: Sinus membrane thickness has been associated with the incidence of
      membrane perforation during the sinus elevation procedure. Understanding the
      sinus membrane thickness is essential for prevention of this specific surgical
      complication. Therefore, the aim of this retrospective study was to investigate
      the impact of sex, age, and season on the membrane thickness. MATERIALS AND
      METHODS: The charts of 144 healthy patients were included in the study. Cone beam
      computed tomography (CBCT) images from these patients were analyzed to determine
      the sinus membrane thickness in the coronal and sagittal views. Sex, age, and
      season were correlated with the membrane thickness. RESULTS: The mean thickness
      of the sinus membrane was 1.81 +/- 1.66 mm (range: 0.47 to 9.49 mm). In 22.12% of
      the CBCT images, the sinus membrane was not visible. Membrane thickness of less
      than 2 mm was found in 70.8% of the cases. Age was found to be strongly
      correlated (P < .05) with sinus membrane thickness but not sex or season.
      CONCLUSION: Based on CBCT assessment, age was found to be a factor influencing
      sinus membrane thickness but not sex or season.

PMID- 29028854
TI  - Clinical Insights and Emerging Strategies in Managing Cutaneous T-Cell Lymphoma.
AB  - <p>Mycosis Fungoides and Sezary Syndrome, the two most common types of Cutaneous
      T-Cell Lymphoma (CTCL), present many management challenges for dermatologists.
      Here, we provide a comprehensive review of up-to-date literature, guidelines, and
      expert clinical insights. We highlight the updates in the World Health
      Organization Classification of Cutaneous Lymphomas; we summarize the
      epidemiology, including a recently observed stabilization of increasing incidence
      of CTCL in the past decade and increased incidence in males, blacks, and
      veterans; we also provide the most recent updates on prognostic factors for CTCL.
      Utilization of Next-Generation Sequencing and other novel technologies has shed
      light on pathogenic mechanisms of CTCL, including immune dysregulation, antigen
      stimulation, and genomic alterations. CTCL management still remains a significant
      challenge due to lack of standardization of therapies for every stage of the
      disease. We provide a straightforward approach to clinical evaluation, diagnostic
      workup via immunophenotyping and molecular studies, staging guidelines, and
      select treatment strategies in Mycosis Fungoides and Sezary Syndrome. CTCL
      patients require individualized, holistic, and multidisciplinary care, for whom
      addressing management in different skin types and prioritizing quality of life
      issues are essential.</p> <p><em>J Drugs Dermatol. 2017;16(5):405-412.</em></p>.

PMID- 29028855
TI  - Benjamin Button Effect: Recognizable Rejuvenation.
AB  - <p>The "Benjamin Button" effect inspired by the popular motion picture, is used
      to describe the goal of achieving a clearly younger and more attractive, yet
      still natural appearance utilizing noninvasive and minimally invasive therapies
      and procedures. Due to high patient demand for enhancement and rejuvenation of
      the face and body with minimal downtime, there is an ever-increasing number of
      companies developing products and devices, variety of indications, and field of
      practitioners offering them. Each option, including topicals, injectables, and
      devices, promises near magical results. Despite that, a brief review of online
      discussions and media resources reveals both patients complaining of inadequate
      results and celebrities with extreme appearances. For clinical practitioners, it
      is critical to understand the art, science, and economics of noninvasive
      rejuvenation in order to properly evaluate potential patients, set appropriate
      expectations, develop, and provide an effective noninvasive rejuvenation plan to
      achieve a true "Benjamin Button" effect for patients.</p> <p><em>J Drugs
      Dermatol. 2017;16(6 Suppl):s74-76.</em></p>.

PMID- 29028856
TI  - Ethnicity and Aging Skin.
AB  - <p>Aging is a complex process influenced by both extrinsic and intrinsic factors.
      Premature signs of aging due to cumulative UV exposure represent a major concern
      of the cosmetic patient. Skin of color is less susceptible to photodamage and
      thus signs of aging are less pronounced and occur later than in Caucasians.
      Understanding structural and functional differences among different racial/ethnic
      groups is important to achieve favorable treatment outcomes when addressing aging
      concerns.</p> <p><em<J Drugs Dermatol. 2017;16(6 Suppl):s77-80.</em></p>.

PMID- 29028858
TI  - Approach to the Mature Cosmetic Patient: Aging Gracefully.
AB  - <p>Aging gracefully has taken on a whole new meaning over the past few decades as
      new aesthetic treatments have been developed and are becoming more sophisticated
      by the day. The aging process, which is exacerbated by chronic UV exposure,
      results in dyspigmentation, loss of skin laxity, precancerous and cancerous skin
      lesions, fat loss and redistribution, and bone resorption. Laser and light
      devices can be used to treat dyspigmentation, while neuromodulators and soft
      tissue fillers can be used for rhytides and revolumization. Newer procedures
      include using resorbable polyglycolide/L-lactide suspension sutures with
      bidirectional cones for mid face revolumization, deoxycholic acid injections for
      submental fat reduction, and radiofrequency energy. Certain over-the-counter
      products can increase the risk of postprocedure bruising, while arnica and
      bromelain may help decrease this risk. Dermatologists continue to be at the
      forefront of aesthetic treatments, ready and willing to help the aging population
      look and feel their best.</p> <p><em>J Drugs Dermatol. 2017;16(6 Suppl):s84
      86.</em></p>.

PMID- 29028857
TI  - Treating the Young Aesthetic Patient: Evidence-Based Recommendations.
AB  - <p>BACKGROUND: There is growing demand for cosmetic treatments in the younger
      population, yet counseling and treating this age group can be difficult to
      justify.</p> <p>OBJECTIVE: Chronologic changes that cause noticeable signs of
      aging are discussed within each age group. Age-appropriate cosmetic preventions
      and interventions are therefore recommended.</p> <p>METHODS: A PubMed search was
      performed for high quality trials and evidence based reviews on the basic science
      of aging, as well as on cosmetic modalities and their histological, biochemical,
      and clinical effects.</p> <p>RESULTS AND CONCLUSIONS: Specific age-related
      changes occur with each decade of life. A complete understanding of when these
      physiologic changes occur helps determine age-appropriate cosmetic counseling,
      preventions, and interventions.</p> <p><em>J Drugs Dermatol. 2017;16(6 Suppl):s81
      83.</em></p>.

PMID- 29028859
TI  - Neurotoxins: Evidence for Prevention.
AB  - <p>Onabotulinum Toxin A is the gold standard treatment for temporary dynamic
      rhytid reduction. Clinicians have observed a long-term and preventive benefit for
      patients beyond muscle relaxation particularly in patients who receive repeated
      treatments over time. These changes include progressive reduction of rhytides,
      prevention of dynamic rhytides, and improvements in skin quality. In this brief
      paper, we review basic science, clinical, and anecdotal evidence that explores a
      long-term and potential preventive effect of Onabotulinum Toxin A injections.</p>
      <p><em>J Drugs Dermatol. 2017;16(6 Suppl):s87-90.</em></p>.

PMID- 29028860
TI  - "Man-some": A Review of Male Facial Aging and Beauty.
AB  - <p>Gender plays a significant role in determining facial anatomy and behavior,
      both of which are key factors in the aging process. Understanding the pattern of
      male facial aging is critical when planning aesthetic treatments on men. Men
      develop more severe rhytides in a unique pattern, show increased periocular aging
      changes, and are more prone to hair loss. What also needs to be considered when
      planning a treatment is what makes men beautiful or "man-some". Male beauty
      strikes a balance between masculine and feminine facial features. A
      hypermasculine face can have negative associations. Men also exhibit different
      cosmetic concerns. Men tend to focus on three areas of the face - hairline,
      periocular area, and jawline. A comprehensive understanding of the male patient
      including anatomy, facial aging, cosmetic concerns, and beauty are needed for
      successful cosmetic outcomes.</p> <p><em>J Drugs Dermatol. 2017;16(6 Suppl):s91
      93.</em></p>.

PMID- 29028861
TI  - The Rationale of Anti-Aging Cosmetic Ingredients.
AB  - <p>Anti-aging cosmetics are a mainstay in the skin care regimen irrespective of
      gender or human ethnics. Skin aging involves functional slowdown combined with
      environmental induced alterations. This paper focuses on cosmetic ingredients
      that aim at alleviating the signs of skin aging, with proven/controlled results
      of efficacy. Anti-aging skin care widely benefits from new ingredients and modern
      evaluation methods that can substantiate the effects of innovative products in a
      perceivable and sensitive manner. Our approach in controlling skin aging consists
      of following steps: 1) Developing novel testing methods; 2) Preventing photo
      aging by sunscreens that protect from UV damage; 3) Protecting and restoring skin
      from damage induced by environmental exposure through active ingredients; 4)
      Boosting the cell metabolism and cell renewal to restore skin mechanical
      properties and improved appearance.</p> <p><em>J Drugs Dermatol. 2017;16(6
      Suppl):s94-97.</em></p>.

PMID- 29028862
TI  - Alternatives to Standard Injectables and Devices for Rejuvenation.
AB  - : <p>INTRODUCTION: Looking at alternatives to standard injectables and devices
      for rejuvenation, typical indications for facial rejuvenation are poor skin
      quality, pigmentary changes, and the loss of shape. Looking for effective
      treatments for those indications in the aesthetic field, one can notice a kind of
      "retro"-trend: easy-to-perform, non- or minimally-invasive, low-investment
      requiring procedures are regaining a lot of popularity. And, over time, those
      treatments are becoming well defined and far more specific.</p> <p>OBJECTIVE: To
      discuss an indication-specific full-face concept for facial rejuvenation using
      alternatives to standard injectables and devices for rejuvenation. MATERIALS AND
      METHODS: The strategy of this indication-specific full-face concept is based on a
      three-pillar-principle: regeneration, regulation, and reshaping. In parallel to
      this concept, major indications such as poor skin quality, pigmentary changes,
      and loss of shape and definition are discussed. To address those indications,
      therapeutic principles such as topicals (cosmeceuticals, magistral formulations),
      mesotherapy, needling, chemical peelings, injection lipolysis, and thread lifting
      will be demonstrated.</p> <p>CONCLUSION: As an alternative to standard
      injectables and devices, an indication-specific approach for a concept of full
      face rejuvenation is based on the three-pillar-principle of regeneration,
      regulation, and reshaping by easy-to-perform, non- or minimally-invasive
      procedures for rejuvenation.</p> <p><em>J Drugs Dermatol. 2017;16(6 Suppl):s98
      103.</em></p>.

PMID- 29028863
TI  - The Future of Non-Invasive Rejuvenation Technology: Devices.
AB  - <p>Non-invasive rejuvenation of the skin is performed regularly in many cosmetic
      offices. Using evidence-based medicine, we will review the various technologies
      being used for non-invasive rejuvenation. This includes the use of intense pulsed
      light (IPL), which has been thoroughly studied and shown to be quite useful for
      this type of rejuvenation in removing the red and brown pigments, as well as
      affecting collagen. Fractional lasers, both non-ablative and ablative in nature,
      also can show dramatic improvements in the skin and associated clinical studies
      are reviewed here. Also described are radiofrequency (RF) fractional pin devices
      and RF microneedles used for non-invasive rejuvenation. Picosecond lasers are
      showing very positive results in the non-invasive rejuvenation market. Finally,
      absorbable sutures are being used to lift the skin and add volume in the skin
      over a duration of time. They are quickly becoming more popular.</p> <p><em>J
      Drugs Dermatol. 2017;16(6 Suppl):s104-107.</em></p>.

PMID- 29028864
TI  - Predicting Cognitive Functioning, Activities of Daily Living, and Participation 6
      Months after Mild to Moderate Stroke.
AB  - Objective: Predicting neurocognitive and functional outcomes in stroke is an
      important clinical task, especially in rehabilitation settings. We assessed acute
      predictors of cognitive and functional outcomes 6 months after mild to moderate
      stroke. Methods: We conducted a retrospective analysis of acute clinical data and
      6-month follow-up telephone interviews for 498 mild to moderate stroke patients.
      Predictors were sociodemographic variables, the National Institute of Health
      Stroke Scale (NIHSS), basic physical measures, the Mesulam Cancellation Test, the
      Short Blessed Test (SBT), Trails A/B, and the Boston Naming Test. The outcome
      variables were the Communication, Memory and Thinking, ADL/IADLs, and
      Participation subscales from the Stroke Impact Scale. We conducted four
      hierarchical multiple regression analyses with demographic variables and the
      NIHSS score entered into the first step, followed by physical variables in the
      second step, and neuropsychological variables in the final step. Results:
      Physical variables explained more variance in ADL/IADLs and Participation
      outcomes than in Communication and Memory and Thinking outcomes, while cognitive
      predictors exhibited the opposite trend. The SBT was the only significant
      independent predictor of Communication and Memory and Thinking (p's < .001),
      while the NIHSS was the only measure that significantly predicted ADL/IADLs (p <
      .001) and Participation (p = .002). Poorer performance on screening measures
      predicted worse cognitive and functional outcomes 6 months post-stroke.
      Conclusions: These results support the clinical utility of administering brief
      screening instruments during acute recovery from mild to moderate stroke.
      Neuropsychologists should prioritize performance on screening measures assessing
      acute neurologic status and cognitive dysfunction when making recommendations for
      post-stroke rehabilitation.

PMID- 29028865
TI  - Clinical Ethics in the Context of Deep Brain Stimulation for Movement Disorders.
AB  - Objective: Discuss common clinical ethical challenges encountered in working with
      patients who are candidates for deep brain stimulation (DBS) for the treatment of
      motor symptoms of Parkinson's disease (PD). Method: The relevant literature is
      reviewed and supplemented by descriptive, ethically challenging cases stemming
      from decades of combined experience working on DBS teams. We outline ethical
      arguments and provide pragmatic recommendations to assist neuropsychologists
      working in movement disorder teams. Results: The goals of the pre-operative
      neuropsychological DBS assessment include: (1) identification of potential
      cognitive risk factors; (2) identification of relevant neuropsychiatric or
      neurobehavioral factors; (3) assessment of level of family support; and (4)
      systematic assessment of patient's and family member's goals or expectations for
      DBS. The information gleaned from the pre-operative neuropsychological assessment
      is highly relevant to the most commonly studied clinical ethics challenges
      encountered in DBS: (1) assessment of risk/benefit; (2) determinations regarding
      inclusion/exclusion; (3) autonomy; and (4) patient's perception of benefit and
      quality of life. Conclusions: Neuropsychologists are particularly well poised to
      provide unique and important insights to assist with developing the most
      ethically sound practices that take into account patient's values as well as
      fiduciary responsibilities to the patient, the team, the profession, and the
      broader community.

PMID- 29028867
TI  - How Flexible is the Use of Egocentric Versus Allocentric Frame of Reference in
      the Williams Syndrome Population?
AB  - Objective: This study examined the spontaneous use of allocentric and egocentric
      frames of reference and their flexible use as a function of instructions. Method:
      The computerized spatial reference task created by Heiz and Barisnikov (2015) was
      used. Participants had to choose a frame of reference according to three types of
      instructions: spontaneous, allocentric and egocentric. The performances of 16
      Williams Syndrome participants between 10 and 41 years were compared to those of
      two control groups (chronological age and non-verbal intellectual ability).
      Results: The majority of Williams Syndrome participants did not show a preference
      for a particular frame of reference. When explicitly inviting participants to use
      an allocentric frame of reference, all three groups showed an increased use of
      the allocentric frame of reference. At the same time, an important heterogeneity
      of type of frame of reference used by Williams Syndrome participants was
      observed. Conclusion: Results demonstrate that despite difficulties in the
      spontaneous use of allocentric and egocentric frames of reference, some Williams
      Syndrome participants show flexibility in the use of an allocentric frame of
      reference when an explicit instruction is provided.

PMID- 29028866
TI  - Global and targeted approaches to single-cell transcriptome characterization.
AB  - Analysing transcriptomes of cell populations is a standard molecular biology
      approach to understand how cells function. Recent methodological development has
      allowed performing similar experiments on single cells. This has opened up the
      possibility to examine samples with limited cell number, such as cells of the
      early embryo, and to obtain an understanding of heterogeneity within populations
      such as blood cell types or neurons. There are two major approaches for single
      cell transcriptome analysis: quantitative reverse transcription PCR (RT-qPCR) on
      a limited number of genes of interest, or more global approaches targeting entire
      transcriptomes using RNA sequencing. RT-qPCR is sensitive, fast and arguably more
      straightforward, while whole-transcriptome approaches offer an unbiased
      perspective on a cell's expression status.

PMID- 29028868
TI  - Symplasmic and apoplasmic transport inside feather moss stems of Pleurozium
      schreberi and Hylocomium splendens.
AB  - Background and Aims: The ubiquitous feather mosses Pleurozium schreberi and
      Hylocomium splendens form a thick, continuous boundary layer between the soil and
      the atmosphere, and play important roles in hydrology and nutrient cycling in
      tundra and boreal ecosystems. The water fluxes among these mosses and
      environmental factors controlling them are poorly understood. The aim of this
      study was to investigate whether feather mosses are capable of internal transport
      and to provide a better understanding of species-specific morphological traits
      underlying this function. The impacts of environmental conditions on their
      internal transport rates were also investigated. Methods: Cells involved in water
      and food conduction in P. schreberi and H. splendens were identified by
      transmission electron microscopy. Symplasmic and apoplasmic fluorescent tracers
      were applied to the moss stems to determine the routes of internal short- and
      long-distance transport and the impact of air humidity on the transport rates.
      Key Results: Symplasmic transport over short distances occurs via food-conducting
      cells in both mosses. Pleurozium schreberi is also capable of apoplasmic internal
      long-distance transport via a central strand of hydroids. These are absent in H.
      splendens. Reduced air humidity significantly increased the internal transport of
      both species, and the increase was significantly faster for P. schreberi than for
      H. splendens. Conclusions: Pleurozium schreberi and Hylocomium splendens are
      capable of internal transport but the pathway and conductivity differ due to
      differences in stem anatomy. These results help explain their varying desiccation
      tolerance and possibly their differing physiology and autecology and, ultimately,
      their impact on ecosystem functioning.

PMID- 29028869
TI  - MG-RAST version 4-lessons learned from a decade of low-budget ultra-high
      throughput metagenome analysis.
AB  - As technologies change, MG-RAST is adapting. Newly available software is being
      included to improve accuracy and performance. As a computational service
      constantly running large volume scientific workflows, MG-RAST is the right
      location to perform benchmarking and implement algorithmic or platform
      improvements, in many cases involving trade-offs between specificity, sensitivity
      and run-time cost. The work in [Glass EM, Dribinsky Y, Yilmaz P, et al. ISME J
      2014;8:1-3] is an example; we use existing well-studied data sets as gold
      standards representing different environments and different technologies to
      evaluate any changes to the pipeline. Currently, we use well-understood data sets
      in MG-RAST as platform for benchmarking. The use of artificial data sets for
      pipeline performance optimization has not added value, as these data sets are not
      presenting the same challenges as real-world data sets. In addition, the MG-RAST
      team welcomes suggestions for improvements of the workflow. We are currently
      working on versions 4.02 and 4.1, both of which contain significant input from
      the community and our partners that will enable double barcoding, stronger
      inferences supported by longer-read technologies, and will increase throughput
      while maintaining sensitivity by using Diamond and SortMeRNA. On the technical
      platform side, the MG-RAST team intends to support the Common Workflow Language
      as a standard to specify bioinformatics workflows, both to facilitate development
      and efficient high-performance implementation of the community's data analysis
      tasks.

PMID- 29028870
TI  - An assessment on the uncertainty of the nitrogen to phosphorus ratio as a
      threshold for nutrient limitation in plants.
AB  - Background and Aims: The nitrogen (N) to phosphorus (P) ratio (N:P) has been
      widely used as a threshold for identifying nutrient limitations in terrestrial
      plants; however, the associated reliability has not been well assessed. Methods:
      The uncertainty of nutrient limitations caused by the N:P threshold was evaluated
      using two approaches: fertilization experiments synthesized across multiple
      ecosystems; and random sampling simulation of the impacts of different nutrient
      sufficiencies and deficiencies. Key Results: The fertilization experiment data
      indicated that the types of nutrient limitation determined via N:P thresholds
      were partly inconsistent with the growth responses observed under N and P
      additions, i.e. under N:P thresholds of 14 and 16 (or 10 and 20), 32.5 % (or 16.2
      %) of the data were inconsistent between these two. The random sampling
      simulation suggested that N:P thresholds may indicate N (or P) limitations when
      leaf N (or P) content is sufficient, whereas these thresholds may not indicate N
      (or P) limitations when leaf N (or P) content is deficient. The error risks
      calculated from the sampling simulation presented large fluctuations at small
      sample sizes and decreased as the thresholds of nutrient content sufficiency (or
      deficiency) increased (or decreased). The N:P thresholds of 10 and 20 showed
      lower error risks than the thresholds of 14 and 16. Conclusions: These findings
      highlight that canonical N:P thresholds have the potential to introduce a large
      uncertainty when used to detect plant nutrient limitations, suggesting that the
      error risks should be cautioned in future studies.

PMID- 29028872
TI  - A review of methods and databases for metagenomic classification and assembly.
AB  - Microbiome research has grown rapidly over the past decade, with a proliferation
      of new methods that seek to make sense of large, complex data sets. Here, we
      survey two of the primary types of methods for analyzing microbiome data: read
      classification and metagenomic assembly, and we review some of the challenges
      facing these methods. All of the methods rely on public genome databases, and we
      also discuss the content of these databases and how their quality has a direct
      impact on our ability to interpret a microbiome sample.

PMID- 29028871
TI  - High light aggravates functional limitations of cucumber canopy photosynthesis
      under salinity.
AB  - Background and Aims: Most crop species are glycophytes, and salinity stress is
      one of the most severe abiotic stresses reducing crop yields worldwide. Salinity
      affects plant architecture and physiological functions by different mechanisms,
      which vary largely between crop species and determine the susceptibility or
      tolerance of a crop species to salinity. Methods: Experimental data from
      greenhouse cucumber (Cucumis sativus), a salt-sensitive species, grown under
      three salinity levels were interpreted by combining a functional-structural plant
      model and quantitative limitation analysis of photosynthesis. This approach
      allowed the quantitative dissection of canopy photosynthetic limitations into
      architectural and functional limitations. Functional limitations were further
      dissected into stomatal (Ls), mesophyll (Lm) and biochemical (Lb). Key Results:
      Architectural limitations increased rapidly after the start of the salinity
      treatment and became stronger than the sum of functional limitations (Ls + Lm +
      Lb) under high salinity. Stomatal limitations resulted from ionic effects and
      were much stronger than biochemical limitations, indicating that canopy
      photosynthesis was more limited by the effects of leaf sodium on stomatal
      regulation than on photosynthetic enzymes. Sensitivity analyses suggested that
      the relative importance of salinity effects on architectural and functional
      limitations depends on light conditions, with high light aggravating functional
      limitations through salinity effects on stomatal limitations. Conclusions:
      Salinity tolerance of cucumber is more likely to be improved by traits related to
      leaf growth and stomatal regulation than by traits related to tissue tolerance to
      ion toxicity, especially under high light conditions.

PMID- 29028873
TI  - miRNA in tumour metabolism and why could it be the preferred pathway for energy
      reprograming.
AB  - The current literature on the role of microRNA (miRNA) in tumour metabolism is
      growing, and a number of studies regularly confirm the impact miRNA can have in
      energy reprograming in tumours. However, there remains to be a lack of
      understanding of the larger perspective of the role of miRNA in the metabolism
      story. In the first part of this review, we provide a comprehensive and up-to
      date description of the extensive role of miRNAs in tumour metabolism including
      glucose, lipid and amino acid metabolism. However, in the second part, we aim to
      provide a description of the multidimensional role miRNA can be playing in tumour
      metabolism. Of paramount importance is the role miRNA has in responding to
      metabolic cues and how it can alter cellular state and fate, including cancer
      stem cells, in response to such cues. In addition, exosomal miRNAs can provide
      means by which cells can communicate metabolic signals and messages with other
      cells within the tumour microenvironment, altering therefore the phenotype and
      functional capacity of these cells. With this expanding area of research better
      understanding of the role of miRNA in tumour metabolism in a mechanistic
      approach, and not only describing which miRNAs can effect which genes, can help
      to exploit the therapeutic implications behind the extensive role of miRNA in
      tumour metabolism.

PMID- 29028874
TI  - Impaired Self-Awareness of Motor Disturbances in Parkinson's Disease.
AB  - Traditionally, anosognosia for cognitive or motor impairments in patients with
      Parkinson's disease (PD) was viewed as unlikely unless the patient was demented.
      More recent research has suggested that a portion of non-demented PD patients
      (30%-50%) in fact have impaired subjective awareness (ISA) of their motor
      impairments (ISAm). This empirical finding has implications for the clinical
      neuropsychological examination of PD patients and raises theoretical questions
      relevant to the broader study of anosognosia seen in other patient groups. The
      purpose of this paper is to primarily review our own research in this area and to
      summarize research findings of other investigators who have examined ISA in PD
      patients. Our secondary goal is to demonstrate the relevance of assessing ISA
      when conducting a neuropsychological examination of PD patients. Our findings
      suggest ISAm in PD patients is related to motor signs of right hemispheric
      dysfunction, but the brain imaging correlates of ISA for hypokinesias appear
      different than those obtained for ISA for dyskinesia in this patient group.

PMID- 29028875
TI  - Systematic bias of correlation coefficient may explain negative accuracy of
      genomic prediction.

PMID- 29028876
TI  - Systematic comparative study of computational methods for T-cell receptor
      sequencing data analysis.
AB  - High-throughput sequencing technologies have exposed the possibilities for the in
      depth evaluation of T-cell receptor (TCR) repertoires. These studies are highly
      relevant to gain insights into human adaptive immunity and to decipher the
      composition and diversity of antigen receptors in physiological and disease
      conditions. The major objective of TCR sequencing data analysis is the
      identification of V, D and J gene segments, complementarity-determining region 3
      (CDR3) sequence extraction and clonality analysis. With the advancement in
      sequencing technologies, new TCR analysis approaches and programs have been
      developed. However, there is still a deficit of systematic comparative studies to
      assist in the selection of an optimal analysis approach. Here, we present a
      detailed comparison of 10 state-of-the-art TCR analysis tools on samples with
      different complexities by taking into account many aspects such as clonotype
      detection [unique V(D)J combination], CDR3 identification or accuracy in error
      correction. We used our in silico and experimental data sets with known
      clonalities enabling the identification of potential tool biases. We also
      established a new strategy, named clonal plane, which allows quantifying and
      comparing the clonality of multiple samples. Our results provide new insights
      into the effect of method selection on analysis results, and it will assist users
      in the selection of an appropriate analysis method.

PMID- 29028877
TI  - RINspector: a Cytoscape app for centrality analyses and DynaMine flexibility
      prediction.
AB  - Motivation: Protein function is directly related to amino acid residue
      composition and the dynamics of these residues. Centrality analyses based on
      residue interaction networks permit to identify key residues in a protein that
      are important for its fold or function. Such central residues and their
      environment constitute suitable targets for mutagenesis experiments. Predicted
      flexibility and changes in flexibility upon mutation provide valuable additional
      information for the design of such experiments. Results: We combined centrality
      analyses with DynaMine flexibility predictions in a Cytoscape app called
      RINspector. The app performs centrality analyses and directly visualizes the
      results on a graph of predicted residue flexibility. In addition, the effect of
      mutations on local flexibility can be calculated. Availability: The app is
      publicly available in the Cytoscape app store. Contact: guillaume.brysbaert@univ
      lille1.fr. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 29028878
TI  - Web-based drug repurposing tools: a survey.
AB  - Drug repurposing (a.k.a. drug repositioning) is the search for new indications or
      molecular targets distinct from a drug's putative activity, pharmacological
      effect or binding specificities. With the ever-increasing rates of termination of
      drugs in clinical trials, drug repositioning has risen as one of the effective
      solutions against the risk of drug failures. Repositioning finds a way to reverse
      the grim but real trend that Eroom's law portends for the pharmaceutical and
      biotech industry, and drug discovery in general. Further, the advent of high
      throughput technologies to explore biological systems has enabled the generation
      of zeta bytes of data and a massive collection of databases that store them.
      Computational analytics and mining are frequently used as effective tools to
      explore this byzantine series of biological and biomedical data. However,
      advanced computational tools are often difficult to understand or use, thereby
      limiting their accessibility to scientists without a strong computational
      background. Hence it is of great importance to build user-friendly interfaces to
      extend the user-base beyond computational scientists, to include life scientists
      who may have deeper chemical and biological insights. This survey is focused on
      systematically presenting the available Web-based tools that aid in repositioning
      drugs.

PMID- 29028879
TI  - Review of computational methods for virus-host protein interaction prediction: a
      case study on novel Ebola-human interactions.
AB  - Identification of potential virus-host interactions is useful and vital to
      control the highly infectious virus-caused diseases. This may contribute toward
      development of new drugs to treat the viral infections. Recently, database
      records of clinically and experimentally validated interactions between a small
      set of human proteins and Ebola virus (EBOV) have been published. Using the
      information of the known human interaction partners of EBOV, our main objective
      is to identify a set of proteins that may interact with EBOV proteins. Here, we
      first review the state-of-the-art, computational methods used for prediction of
      novel virus-host interactions for infectious diseases followed by a case study on
      EBOV-human interactions. The assessment result shows that the predicted human
      host proteins are highly similar with known human interaction partners of EBOV in
      the context of structure and semantics and are responsible for similar
      biochemical activities, pathways and host-pathogen relationships.

PMID- 29028881
TI  - SNP genotyping and parameter estimation in polyploids using low-coverage
      sequencing data.
AB  - Motivation: Genotyping and parameter estimation using high throughput sequencing
      data are everyday tasks for population geneticists, but methods developed for
      diploids are typically not applicable to polyploid taxa. This is due to their
      duplicated chromosomes, as well as the complex patterns of allelic exchange that
      often accompany whole genome duplication (WGD) events. For WGDs within a single
      lineage (autopolyploids), inbreeding can result from mixed mating and/or double
      reduction. For WGDs that involve hybridization (allopolyploids), alleles are
      typically inherited through independently segregating subgenomes. Results: We
      present two new models for estimating genotypes and population genetic parameters
      from genotype likelihoods for auto- and allopolyploids. We then use simulations
      to compare these models to existing approaches at varying depths of sequencing
      coverage and ploidy levels. These simulations show that our models typically have
      lower levels of estimation error for genotype and parameter estimates, especially
      when sequencing coverage is low. Finally, we also apply these models to two
      empirical datasets from the literature. Overall, we show that the use of genotype
      likelihoods to model non-standard inheritance patterns is a promising approach
      for conducting population genomic inferences in polyploids. Availability and
      implementation: A C ++ program, EBG, is provided to perform inference using the
      models we describe. It is available under the GNU GPLv3 on GitHub:
      https://github.com/pblischak/polyploid-genotyping. Contact: blischak.4@osu.edu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29028880
TI  - Semantic Memory in HIV-associated Neurocognitive Disorders: An Evaluation of the
      "Cortical" Versus "Subcortical" Hypothesis.
AB  - Objective: HIV-associated neurocognitive disorders (HAND) have historically been
      characterized as a subcortical condition that does not affect semantic memory;
      however, recent evidence suggests that the cortical regions that support semantic
      memory may be affected in HIV. Method: The current study examined the effects of
      HAND on semantic memory in 85 HIV+ individuals with HAND, 193 HIV+ individuals
      without HAND, and 181 HIV- individuals who completed the Boston Naming Test (BNT)
      and the Famous Faces subtest of the Kauffman Adolescent and Adult Intelligence
      Test (KAIT-FF). Results: Linear regressions revealed a significant adverse effect
      of HAND on total scores on the BNT and the KAIT-FF (all ps < .01). Analyses of
      BNT errors showed that individuals with HAND committed more semantically related
      errors as compared to the other two study groups (all ps < .05). However, there
      were no group differences in rates of visually based errors, which are more
      commonly observed in traditional subcortical diseases (all ps > .10).
      Conclusions: Results indicate that HAND may impose adverse effects on
      individuals' object naming and identification abilities suggestive of mild
      semantic deficits that parallel traditional cortical diseases such as Alzheimer's
      disease.

PMID- 29028882
TI  - Enzymatic methods for genome-wide profiling of protein binding sites.
AB  - Genome-wide mapping of protein-DNA interactions is a staple approach in many
      areas of modern molecular biology. Genome-wide profiles of protein-binding sites
      are most commonly generated by chromatin immunoprecipitation and high-throughput
      sequencing (ChIP-seq). Although ChIP-seq has played a central role in studying
      genome-wide protein binding, recent work has highlighted systematic biases in the
      technique that warrant technical and interpretive caution and underscore the need
      for orthogonal techniques to both confirm the results of ChIP-seq studies and
      uncover new insights not accessible to ChIP. Several such techniques, based on
      genetic or immunological targeting of enzymatic activity to specific genomic
      loci, have been developed. Here, we review the development, applications and
      future prospects of these methods as complements to ChIP-based approaches and as
      powerful techniques in their own right.

PMID- 29028883
TI  - A new pan-European Train-the-Trainer programme for bioinformatics: pilot results
      on feasibility, utility and sustainability of learning.
AB  - Demand for training life scientists in bioinformatics methods, tools and
      resources and computational approaches is urgent and growing. To meet this
      demand, new trainers must be prepared with effective teaching practices for
      delivering short hands-on training sessions-a specific type of education that is
      not typically part of professional preparation of life scientists in many
      countries. A new Train-the-Trainer (TtT) programme was created by adapting
      existing models, using input from experienced trainers and experts in
      bioinformatics, and from educational and cognitive sciences. This programme was
      piloted across Europe from May 2016 to January 2017. Preparation included
      drafting the training materials, organizing sessions to pilot them and studying
      this paradigm for its potential to support the development and delivery of future
      bioinformatics training by participants. Seven pilot TtT sessions were carried
      out, and this manuscript describes the results of the pilot year. Lessons learned
      include (i) support is required for logistics, so that new instructors can focus
      on their teaching; (ii) institutions must provide incentives to include training
      opportunities for those who want/need to become new or better instructors; (iii)
      formal evaluation of the TtT materials is now a priority; (iv) a strategy is
      needed to recruit, train and certify new instructor trainers (faculty); and (v)
      future evaluations must assess utility. Additionally, defining a flexible but
      rigorous and reliable process of TtT 'certification' may incentivize participants
      and will be considered in future.

PMID- 29028885
TI  - HoTResDB: Host Transcriptional Response Database for Viral Hemorrhagic Fevers.
AB  - Summary: High-throughput screening of the host transcriptional response to
      various viral infections provides a wealth of data but utilization of microarray
      and next generation sequencing (NGS) data for analysis can be difficult. The Host
      Transcriptional Response DataBase (HoTResDB), allows visitors to access already
      processed microarray and NGS data from non-human primate models of viral
      hemorrhagic fever to better understand the host transcriptional response.
      Availability: HoTResDB is freely available at http://hotresdb.bu.edu. Contact:
      jhconnor@bu.edu. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 29028886
TI  - Analysis of protein targets in pathogen-host interaction in infectious diseases:
      a case study on Plasmodium falciparum and Homo sapiens interaction network.
AB  - Infection and disease progression is the outcome of protein interactions between
      pathogen and host. Pathogen, the role player of Infection, is becoming a severe
      threat to life as because of its adaptability toward drugs and evolutionary
      dynamism in nature. Identifying protein targets by analyzing protein interactions
      between host and pathogen is the key point. Proteins with higher degree and
      possessing some topologically significant graph theoretical measures are found to
      be drug targets. On the other hand, exceptional nodes may be involved in
      infection mechanism because of some pathway process and biologically unknown
      factors. In this article, we attempt to investigate characteristics of host
      pathogen protein interactions by presenting a comprehensive review of
      computational approaches applied on different infectious diseases. As an
      illustration, we have analyzed a case study on infectious disease malaria, with
      its causative agent Plasmodium falciparum acting as 'Bait' and host, Homo
      sapiens/human acting as 'Prey'. In this pathogen-host interaction network based
      on some interconnectivity and centrality properties, proteins are viewed as
      central, peripheral, hub and non-hub nodes and their significance on infection
      process. Besides, it is observed that because of sparseness of the pathogen and
      host interaction network, there may be some topologically unimportant but
      biologically significant proteins, which can also act as Bait/Prey. So,
      functional similarity or gene ontology mapping can help us in this case to
      identify these proteins.

PMID- 29028884
TI  - Protein-protein interaction specificity is captured by contact preferences and
      interface composition.
AB  - Motivation: Large-scale computational docking will be increasingly used in future
      years to discriminate protein-protein interactions at the residue resolution.
      Complete cross-docking experiments make in silico reconstruction of protein
      protein interaction networks a feasible goal. They ask for efficient and accurate
      screening of the millions structural conformations issued by the calculations.
      Results: We propose CIPS (Combined Interface Propensity for decoy Scoring), a new
      pair potential combining interface composition with residue-residue contact
      preference. CIPS outperforms several other methods on screening docking solutions
      obtained either with all-atom or with coarse-grain rigid docking. Further testing
      on 28 CAPRI targets corroborates CIPS predictive power over existing methods. By
      combining CIPS with atomic potentials, discrimination of correct conformations in
      all-atom structures reaches optimal accuracy. The drastic reduction of candidate
      solutions produced by thousands of proteins docked against each other makes large
      scale docking accessible to analysis. Availability and implementation: CIPS
      source code is freely available at http://www.lcqb.upmc.fr/CIPS. Contact:
      alessandra.carbone@lip6.fr. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29028887
TI  - Identification of cancer driver genes in focal genomic aberrations from whole
      exome sequencing data.
AB  - Summary: Whole-exome sequencing (WES) data have been used for identifying copy
      number aberrations in cancer cells. Nonetheless, the use of WES is still
      challenging for identification of focal aberrant regions in multiple samples that
      may contain cancer driver genes. In this study, we developed a wavelet-based
      method for identifying focal genomic aberrant regions in the WES data from cancer
      cells (WIFA-X). When we applied WIFA-X to glioblastoma multiforme and lung
      adenocarcinoma datasets, WIFA-X outperformed other approaches on identifying
      cancer driver genes. Availability and implementation: R source code is available
      at http://gcancer.org/wifax. Contact: hyunjulee@gist.ac.kr. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29028888
TI  - RRDB: a comprehensive and non-redundant benchmark for RNA-RNA docking and
      scoring.
AB  - Motivation: With the discovery of more and more noncoding RNAs and their
      versatile functions, RNA-RNA interactions have received increased attention.
      Therefore, determination of their complex structures is valuable to understand
      the molecular mechanism of the interactions. Given the high cost of experimental
      methods, computational approaches like molecular docking have played an important
      role in the determination of complex structures, in which a benchmark is critical
      for the development of docking algorithms. Results: Meeting the need, we have
      developed the first comprehensive and nonredundant RNA-RNA docking benchmark
      (RRDB). The diverse dataset of 123 targets consists of 78 unbound-unbound and 45
      bound-unbound (or unbound-bound) test cases. The dataset was classified into
      three groups according to the interface conformational changes between bound and
      unbound structures: 47 'easy', 38 'medium' and 38 'difficult' targets. A docking
      test with the benchmark using ZDOCK 2.1 demonstrated the challenging nature of
      the RNA-RNA docking problem and the important value of the present benchmark. The
      bound and unbound cases of the benchmark will be beneficial for the development
      and optimization of docking and scoring algorithms for RNA-RNA interactions.
      Availability and implementation: The benchmark is available at
      http://huanglab.phys.hust.edu.cn/RRDbenchmark/. Contact: huangsy@hust.edu.cn.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29028889
TI  - Segway 2.0: Gaussian mixture models and minibatch training.
AB  - Summary: Segway performs semi-automated genome annotation, discovering joint
      patterns across multiple genomic signal datasets. We discuss a major new version
      of Segway and highlight its ability to model data with substantially greater
      accuracy. Major enhancements in Segway 2.0 include the ability to model data with
      a mixture of Gaussians, enabling capture of arbitrarily complex signal
      distributions, and minibatch training, leading to better learned parameters.
      Availability and implementation: Segway and its source code are freely available
      for download at http://segway.hoffmanlab.org. We have made available scripts
      (https://doi.org/10.5281/zenodo.802939) and datasets
      (https://doi.org/10.5281/zenodo.802906) for this paper's analysis. Contact:
      michael.hoffman@utoronto.ca. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29028890
TI  - MALDIrppa: quality control and robust analysis for mass spectrometry data.
AB  - Summary: This R package helps to implement a robust approach to deal with mass
      spectrometry (MS) data. It is aimed at alleviating reproducibility issues and
      pernicious effects of deviating signals on both data pre-processing and
      downstream data analysis. Based on robust statistical methods, it facilitates the
      identification and filtering of low-quality mass spectra and atypical peak
      profiles as well as monitoring and data handling through pre-processing, which
      extends existing computational tools for high-throughput data. Availability and
      implementation: MALDIrppa is implemented as a package for the R environment for
      data analysis and it is freely available to download from the CRAN repository at
      https://CRAN.R-project.org/package=MALDIrppa. Contact:
      javier.palarea@bioss.ac.uk.

PMID- 29028891
TI  - On the mechanisms of protein interactions: predicting their affinity from unbound
      tertiary structures.
AB  - Motivation: The characterization of the protein-protein association mechanisms is
      crucial to understanding how biological processes occur. It has been previously
      shown that the early formation of non-specific encounters enhances the
      realization of the stereospecific (i.e. native) complex by reducing the
      dimensionality of the search process. The association rate for the formation of
      such complex plays a crucial role in the cell biology and depends on how the
      partners diffuse to be close to each other. Predicting the binding free energy of
      proteins provides new opportunities to modulate and control protein-protein
      interactions. However, existing methods require the 3D structure of the complex
      to predict its affinity, severely limiting their application to interactions with
      known structures. Results: We present a new approach that relies on the unbound
      protein structures and protein docking to predict protein-protein binding
      affinities. Through the study of the docking space (i.e. decoys), the method
      predicts the binding affinity of the query proteins when the actual structure of
      the complex itself is unknown. We tested our approach on a set of globular and
      soluble proteins of the newest affinity benchmark, obtaining accuracy values
      comparable to other state-of-art methods: a 0.4 correlation coefficient between
      the experimental and predicted values of DeltaG and an error < 3 Kcal/mol.
      Availability and implementation: The binding affinity predictor is implemented
      and available at http://sbi.upf.edu/BADock and
      https://github.com/badocksbi/BADock. Contact: j.planas-iglesias@warwick.ac.uk or
      baldo.oliva@upf.edu. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29028892
TI  - Nephele: a cloud platform for simplified, standardized and reproducible
      microbiome data analysis.
AB  - Motivation: Widespread interest in the study of the microbiome has resulted in
      data proliferation and the development of powerful computational tools. However,
      many scientific researchers lack the time, training, or infrastructure to work
      with large datasets or to install and use command line tools. Results: The
      National Institute of Allergy and Infectious Diseases (NIAID) has created
      Nephele, a cloud-based microbiome data analysis platform with standardized
      pipelines and a simple web interface for transforming raw data into biological
      insights. Nephele integrates common microbiome analysis tools as well as valuable
      reference datasets like the healthy human subjects cohort of the Human Microbiome
      Project (HMP). Nephele is built on the Amazon Web Services cloud, which provides
      centralized and automated storage and compute capacity, thereby reducing the
      burden on researchers and their institutions. Availability and implementation:
      https://nephele.niaid.nih.gov and https://github.com/niaid/Nephele. Contact:
      darrell.hurt@nih.gov.

PMID- 29028893
TI  - Canvas SPW: calling de novo copy number variants in pedigrees.
AB  - Motivation: Whole genome sequencing is becoming a diagnostics of choice for the
      identification of rare inherited and de novo copy number variants in families
      with various pediatric and late-onset genetic diseases. However, joint variant
      calling in pedigrees is hampered by the complexity of consensus breakpoint
      alignment across samples within an arbitrary pedigree structure. Results: We have
      developed a new tool, Canvas SPW, for the identification of inherited and de novo
      copy number variants from pedigree sequencing data. Canvas SPW supports a number
      of family structures and provides a wide range of scoring and filtering options
      to automate and streamline identification of de novo variants. Availability and
      implementation: Canvas SPW is available for download from
      https://github.com/Illumina/canvas. Contact: sivakhno@illumina.com. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29028894
TI  - AQUa: an adaptive framework for compression of sequencing quality scores with
      random access functionality.
AB  - Motivation: The past decade has seen the introduction of new technologies that
      significantly lowered the cost of genome sequencing. As a result, the amount of
      genomic data that must be stored and transmitted is increasing exponentially. To
      mitigate storage and transmission issues, we introduce a framework for lossless
      compression of quality scores. Results: This article proposes AQUa, an adaptive
      framework for lossless compression of quality scores. To compress these quality
      scores, AQUa makes use of a configurable set of coding tools, extended with a
      Context-Adaptive Binary Arithmetic Coding scheme. When benchmarking AQUa against
      generic single-pass compressors, file sizes are reduced by up to 38.49% when
      comparing with GNU Gzip and by up to 6.48% when comparing with 7-Zip at the Ultra
      Setting, while still providing support for random access. When comparing AQUa
      with the purpose-built, single-pass, and state-of-the-art compressor SCALCE,
      which does not support random access, file sizes are reduced by up to 21.14%.
      When comparing AQUa with the purpose-built, dual-pass, and state-of-the-art
      compressor QVZ, which does not support random access, file sizes are larger by
      6.42-33.47%. However, for one test file, the file size is 0.38% smaller,
      illustrating the strength of our single-pass compression framework. This work has
      been spurred by the current activity on genomic information representation (MPEG
      G) within the ISO/IEC SC29/WG11 technical committee. Availability and
      implementation: The software is available on Github:
      https://github.com/tparidae/AQUa. Contact: tom.paridaens@ugent.be.

PMID- 29028895
TI  - CCmiR: A computational approach for competitive and cooperative microRNA binding
      prediction.
AB  - Motivation: The identification of microRNA (miRNA) target sites is important. In
      the past decade, dozens of computational methods have been developed to predict
      miRNA target sites. Despite their existence, rarely does a method consider the
      well-known competition and cooperation among miRNAs when attempts to discover
      target sites. To fill this gap, we developed a new approach called CCmiR, which
      takes the cooperation and competition of multiple miRNAs into account in a
      statistical model to predict their target sites. Results: Tested on four
      different datasets, CCmiR predicted miRNA target sites with a high recall and a
      reasonable precision, and identified known and new cooperative and competitive
      miRNAs supported by literature. Compared with three state-of-the-art
      computational methods, CCmiR had a higher recall and a higher precision.
      Availability: CCmiR is freely available at
      http://hulab.ucf.edu/research/projects/miRNA/CCmiR. Contact:
      xiaoman@mail.ucf.edu, haihu@cs.ucf.edu. Supplementary information: Supplementary
      data are available at Bioinformatics online.

PMID- 29028896
TI  - PyDREAM: high-dimensional parameter inference for biological models in python.
AB  - Summary: Biological models contain many parameters whose values are difficult to
      measure directly via experimentation and therefore require calibration against
      experimental data. Markov chain Monte Carlo (MCMC) methods are suitable to
      estimate multivariate posterior model parameter distributions, but these methods
      may exhibit slow or premature convergence in high-dimensional search spaces.
      Here, we present PyDREAM, a Python implementation of the (Multiple-Try)
      Differential Evolution Adaptive Metropolis [DREAM(ZS)] algorithm developed by
      Vrugt and ter Braak (2008) and Laloy and Vrugt (2012). PyDREAM achieves excellent
      performance for complex, parameter-rich models and takes full advantage of
      distributed computing resources, facilitating parameter inference and uncertainty
      estimation of CPU-intensive biological models. Availability and implementation:
      PyDREAM is freely available under the GNU GPLv3 license from the Lopez lab GitHub
      repository at http://github.com/LoLab-VU/PyDREAM. Contact:
      c.lopez@vanderbilt.edu. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29028897
TI  - Sipros Ensemble improves database searching and filtering for complex
      metaproteomics.
AB  - Motivation: Complex microbial communities can be characterized by metagenomics
      and metaproteomics. However, metagenome assemblies often generate enormous, and
      yet incomplete, protein databases, which undermines the identification of
      peptides and proteins in metaproteomics. This challenge calls for increased
      discrimination of true identifications from false identifications by database
      searching and filtering algorithms in metaproteomics. Results: Sipros Ensemble
      was developed here for metaproteomics using an ensemble approach. Three diverse
      scoring functions from MyriMatch, Comet and the original Sipros were incorporated
      within a single database searching engine. Supervised classification with
      logistic regression was used to filter database searching results. Benchmarking
      with soil and marine microbial communities demonstrated a higher number of
      peptide and protein identifications by Sipros Ensemble than MyriMatch/Percolator,
      Comet/Percolator, MS-GF+/Percolator, Comet & MyriMatch/iProphet and Comet &
      MyriMatch & MS-GF+/iProphet. Sipros Ensemble was computationally efficient and
      scalable on supercomputers. Availability and implementation: Freely available
      under the GNU GPL license at http://sipros.omicsbio.org. Contact: cpan@utk.edu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29028898
TI  - diffloop: a computational framework for identifying and analyzing differential
      DNA loops from sequencing data.
AB  - Summary: The 3D architecture of DNA within the nucleus is a key determinant of
      interactions between genes, regulatory elements, and transcriptional machinery.
      As a result, differences in DNA looping structure are associated with variation
      in gene expression and cell state. To systematically assess changes in DNA
      looping architecture between samples, we introduce diffloop, an R/Bioconductor
      package that provides a suite of functions for the quality control, statistical
      testing, annotation, and visualization of DNA loops. We demonstrate this
      functionality by detecting differences between ENCODE ChIA-PET samples and relate
      looping to variability in epigenetic state. Availability and implementation:
      Diffloop is implemented as an R/Bioconductor package available at
      https://bioconductor.org/packages/release/bioc/html/diffloop.html. Contact:
      aryee.martin@mgh.harvard.edu. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29028899
TI  - Phandango: an interactive viewer for bacterial population genomics.
AB  - Summary: Fully exploiting the wealth of data in current bacterial population
      genomics datasets requires synthesising and integrating different types of
      analysis across millions of base pairs in hundreds or thousands of isolates.
      Current approaches often use static representations of phylogenetic,
      epidemiological, statistical and evolutionary analysis results that are difficult
      to relate to one another. Phandango is an interactive application running in a
      web browser allowing fast exploration of large-scale population genomics datasets
      combining the output from multiple genomic analysis methods in an intuitive and
      interactive manner. Availability: Phandango is a web application freely available
      for use at www.phandango.net and includes a diverse collection of datasets as
      examples. Source code together with a detailed wiki page is available on GitHub
      at https://github.com/jameshadfield/phandango. Contact: jh22@sanger.ac.uk,
      sh16@sanger.ac.uk.

PMID- 29028901
TI  - A collaborative filtering-based approach to biomedical knowledge discovery.
AB  - Motivation: The increase in publication rates makes it challenging for an
      individual researcher to stay abreast of all relevant research in order to find
      novel research hypotheses. Literature-based discovery methods make use of
      knowledge graphs built using text mining and can infer future associations
      between biomedical concepts that will likely occur in new publications. These
      predictions are a valuable resource for researchers to explore a research topic.
      Current methods for prediction are based on the local structure of the knowledge
      graph. A method that uses global knowledge from across the knowledge graph needs
      to be developed in order to make knowledge discovery a frequently used tool by
      researchers. Results: We propose an approach based on the singular value
      decomposition (SVD) that is able to combine data from across the knowledge graph
      through a reduced representation. Using cooccurrence data extracted from
      published literature, we show that SVD performs better than the leading methods
      for scoring discoveries. We also show the diminishing predictive power of
      knowledge discovery as we compare our predictions with real associations that
      appear further into the future. Finally, we examine the strengths and weaknesses
      of the SVD approach against another well-performing system using several
      predicted associations. Availability and implementation: All code and results
      files for this analysis can be accessed at
      https://github.com/jakelever/knowledgediscovery. Contact: sjones@bcgsc.ca.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29028902
TI  - graphkernels: R and Python packages for graph comparison.
AB  - Summary: Measuring the similarity of graphs is a fundamental step in the analysis
      of graph-structured data, which is omnipresent in computational biology. Graph
      kernels have been proposed as a powerful and efficient approach to this problem
      of graph comparison. Here we provide graphkernels, the first R and Python graph
      kernel libraries including baseline kernels such as label histogram based
      kernels, classic graph kernels such as random walk based kernels, and the state
      of-the-art Weisfeiler-Lehman graph kernel. The core of all graph kernels is
      implemented in C ++ for efficiency. Using the kernel matrices computed by the
      package, we can easily perform tasks such as classification, regression and
      clustering on graph-structured samples. Availability and implementation: The R
      and Python packages including source code are available at https://CRAN.R
      project.org/package=graphkernels and https://pypi.python.org/pypi/graphkernels.
      Contact: mahito@nii.ac.jp or elisabetta.ghisu@bsse.ethz.ch. Supplementary
      information: Supplementary data are available online at Bioinformatics.

PMID- 29028903
TI  - Comparative analysis of differential gene expression tools for RNA sequencing
      time course data.
AB  - RNA sequencing (RNA-seq) has become a standard procedure to investigate
      transcriptional changes between conditions and is routinely used in research and
      clinics. While standard differential expression (DE) analysis between two
      conditions has been extensively studied, and improved over the past decades, RNA
      seq time course (TC) DE analysis algorithms are still in their early stages. In
      this study, we compare, for the first time, existing TC RNA-seq tools on an
      extensive simulation data set and validated the best performing tools on
      published data. Surprisingly, TC tools were outperformed by the classical
      pairwise comparison approach on short time series (<8 time points) in terms of
      overall performance and robustness to noise, mostly because of high number of
      false positives, with the exception of ImpulseDE2. Overlapping of candidate lists
      between tools improved this shortcoming, as the majority of false-positive, but
      not true-positive, candidates were unique for each method. On longer time series,
      pairwise approach was less efficient on the overall performance compared with
      splineTC and maSigPro, which did not identify any false-positive candidate.

PMID- 29028900
TI  - Unravelling the biological secrets of microchimerism by single-cell analysis.
AB  - The presence of microchimeric cells is known for >100 years and well documented
      since decades. Earlier, microchimeric cells were mainly used for cell-based non
      invasive prenatal diagnostics during early pregnancy. Microchimeric cells are
      also present beyond delivery and are associated to various autoimmune diseases,
      tissue repair, cancer and immune tolerance. All these findings were based on low
      complexity studies and occasionally accompanied by artefacts not allowing the
      biological functions of microchimerism to be determined. However, with the recent
      developments in single-cell analysis, new means to identify and characterize
      microchimeric cells are available. Cell labelling techniques in combination with
      single-cell analysis provide a new toolbox to decipher the biology of
      microchimeric cells at molecular and cellular level. In this review, we discuss
      how recent developments in single-cell analysis can be applied to determine the
      role and function of microchimeric cells.

PMID- 29028904
TI  - Considerations for Clinical Neuropsychological Evaluation in Amyotrophic Lateral
      Sclerosis.
AB  - The clinical neuropsychologist has the opportunity to be uniquely involved in the
      evaluation and treatment of individuals with amyotrophic lateral sclerosis (ALS).
      We review the current literature that defines cognitive and behavioral symptoms
      in ALS, including current knowledge of the neuropathological and genetic
      underpinning for these symptoms. There are unique considerations for clinical
      neuropsychological evaluation and clinical research in ALS and we highlight these
      in this review. Specifically, we shed light on special factors that contribute to
      our understanding of cognitive and behavioral impairment in ALS, including co
      morbid symptoms, differential diagnosis, and considerations for longitudinal
      tracking of phenotypes. We discuss the rationale for proposing a specific
      approach to such as cognitive screening, test selection, response modality
      consideration, and test-retest intervals. With this didactic overview, the
      clinical neuropsychologist has the potential to learn more about the
      heterogeneous presentation of motor and neuropsychological symptoms in ALS.
      Furthermore, the reader has the opportunity to understand what it takes to
      develop a valid assessment approach particularly when the phenotype of ALS
      remains undefined in some regards. This clinical practice review sets the stage
      for the clinical neuropsychologist to further contribute to our clinical and
      scientific understanding of ALS and cognition.

PMID- 29028906
TI  - Critical assessment and performance improvement of plant-pathogen protein-protein
      interaction prediction methods.
AB  - The identification of plant-pathogen protein-protein interactions (PPIs) is an
      attractive and challenging research topic for deciphering the complex molecular
      mechanism of plant immunity and pathogen infection. Considering that the
      experimental identification of plant-pathogen PPIs is time-consuming and labor
      intensive, computational methods are emerging as an important strategy to
      complement the experimental methods. In this work, we first evaluated the
      performance of traditional computational methods such as interolog, domain-domain
      interaction and domain-motif interaction in predicting known plant-pathogen PPIs.
      Owing to the low sensitivity of the traditional methods, we utilized Random
      Forest to build an inter-species PPI prediction model based on multiple sequence
      encodings and novel network attributes in the established plant PPI network.
      Critical assessment of the features demonstrated that the integration of sequence
      information and network attributes resulted in significant and robust performance
      improvement. Additionally, we also discussed the influence of Gene Ontology and
      gene expression information on the prediction performance. The Web server
      implementing the integrated prediction method, named InterSPPI, has been made
      freely available at http://systbio.cau.edu.cn/intersppi/index.php. InterSPPI
      could achieve a reasonably high accuracy with a precision of 73.8% and a recall
      of 76.6% in the independent test. To examine the applicability of InterSPPI, we
      also conducted cross-species and proteome-wide plant-pathogen PPI prediction
      tests. Taken together, we hope this work can provide a comprehensive
      understanding of the current status of plant-pathogen PPI predictions, and the
      proposed InterSPPI can become a useful tool to accelerate the exploration of
      plant-pathogen interactions.

PMID- 29028905
TI  - Quality of biological images, reconstructed using localization microscopy data.
AB  - Motivation: Fluorescence localization microscopy is extensively used to study the
      details of spatial architecture of subcellular compartments. This modality relies
      on determination of spatial positions of fluorophores, labeling an extended
      biological structure, with precision exceeding the diffraction limit. Several
      established models describe influence of pixel size, signal-to-noise ratio and
      optical resolution on the localization precision. The labeling density has been
      also recognized as important factor affecting reconstruction fidelity of the
      imaged biological structure. However, quantitative data on combined influence of
      sampling and localization errors on the fidelity of reconstruction are scarce. It
      should be noted that processing localization microscopy data is similar to
      reconstruction of a continuous (extended) non-periodic signal from a non-uniform,
      noisy point samples. In two dimensions the problem may be formulated within the
      framework of matrix completion. However, no systematic approach has been adopted
      in microscopy, where images are typically rendered by representing localized
      molecules with Gaussian distributions (widths determined by localization
      precision). Results: We analyze the process of two-dimensional reconstruction of
      extended biological structures as a function of the density of registered
      emitters, localization precision and the area occupied by the rendered localized
      molecule. We quantify overall reconstruction fidelity with different established
      image similarity measures. Furthermore, we analyze the recovered similarity
      measure in the frequency space for different reconstruction protocols. We compare
      the cut-off frequency to the limiting sampling frequency, as determined by
      labeling density. Availability and implementation: The source code used in the
      simulations along with test images is available at
      https://github.com/blazi13/qbioimages. Contact: bruszczy@nencki.gov.pl or
      t.bernas@nencki.gov.pl. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29028907
TI  - OncomiR: an online resource for exploring pan-cancer microRNA dysregulation.
AB  - Summary: Dysregulation of microRNAs (miRNAs) is extensively associated with
      cancer development and progression. miRNAs have been shown to be biomarkers for
      predicting tumor formation and outcome. However, identification of the
      relationships between miRNA expression and tumor characteristics can be difficult
      and time-consuming without appropriate bioinformatics expertise. To address this
      issue, we present OncomiR, an online resource for exploring miRNA dysregulation
      in cancer. Using combined miRNA-seq, RNA-seq and clinical data from The Cancer
      Genome Atlas, we systematically performed statistical analyses to identify
      dysregulated miRNAs that are associated with tumor development and progression in
      most major cancer types. Additional analyses further identified potential miRNA
      gene target interactions in tumors. These results are stored in a backend
      database and presented through a web server interface. Moreover, through a
      backend bioinformatics pipeline, OncomiR can also perform dynamic analysis with
      custom miRNA selections for in-depth characterization of miRNAs in cancer.
      Availability and implementation: The OncomiR website is freely accessible at
      www.oncomir.org. Contact: xiaowei.wang@wustl.edu. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29028909
TI  - The systematic analysis of ultraconserved genomic regions in the budding yeast.
AB  - Motivation: In the evolution of species, a kind of special sequences, termed
      ultraconserved sequences (UCSs), have been inherited without any change, which
      strongly suggests those sequences should be crucial for the species to survive or
      adapt to the environment. However, the UCSs are still regarded as mysterious
      genetic sequences so far. Here, we present a systematic study of ultraconserved
      genomic regions in the budding yeast based on the publicly available genome
      sequences, in order to reveal their relationship with the adaptability or fitness
      advantages of the budding yeast. Results: Our results indicate that, in addition
      to some fundamental biological functions, the UCSs play an important role in the
      adaptation of Saccharomyces cerevisiae to the acidic environment, which is backed
      up by the previous observation. Besides that, we also find the highly unchanged
      genes are enriched in some other pathways, such as the nutrient-sensitive
      signaling pathway. To facilitate the investigation of unique UCSs, the UCSC
      Genome Browser was utilized to visualize the chromosomal position and related
      annotations of UCSs in S.cerevisiae genome. Availability and implementation: For
      more details on UCSs, please refer to the Supplementary information online, and
      the custom code is available on request. Contact: fgao@tju.edu.cn. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29028908
TI  - Negative Affect Is Associated With Higher Risk of Incident Cognitive Impairment
      in Nondepressed Postmenopausal Women.
AB  - Background: Positive affect (PA) and negative affect (NA) reflect subjective
      emotional experiences. Although related to depression and anxiety, these
      dimensions are distinct constructs representing affective states and patterns.
      Prior studies suggest that elevated depressive symptoms are associated with risk
      of mild cognitive impairment (MCI) and probable dementia, but whether affective
      states are associated with cognitive impairment is still unknown. The present
      study examined relationships between baseline affective states and cognitive
      impairment (MCI, probable dementia) in nondepressed women. Method: Baseline PA
      and NA were assessed in postmenopausal women (N = 2,137; mean age = 73.8 years)
      from the Women's Health Initiative Study of Cognitive Aging (WHISCA) using the
      Positive and Negative Affect Schedule (PANAS). Women were followed annually for
      an average of 11.3 years; those with elevated depressive symptoms at baseline
      were excluded. Results: Higher NA was associated with a higher risk of MCI and
      probable dementia, even after adjusting for important covariates including age,
      education, sociodemographic, lifestyle, and cardiovascular risk factors, global
      cognition, and hormone therapy assignment at baseline. PA was not significantly
      associated with either outcome. Conclusions: We present the first evidence to
      date that greater NA, even in the absence of elevated depressive symptoms, is
      associated with higher risk of MCI and dementia. This suggests that NA may be an
      important, measureable and potentially modifiable risk factor for age-related
      cognitive decline.

PMID- 29028910
TI  - Assessment of changes in lactate concentration with intravascular microdialysis
      during high-risk cardiac surgery using the trend interchangeability method.
AB  - Background: Blood lactate is a strong predictor of mortality, and repeated blood
      lactate assays are recommended during surgery in high-risk patients. We
      hypothesized that the use of intravascular microdialysis incorporated in a
      central venous catheter would be interchangeable with the reference blood gas
      technique to monitor changes in blood lactate. Methods: Microdialysis and central
      venous blood lactate measurements were recorded simultaneously in high-risk
      cardiac surgical patients. The correlation between absolute values was determined
      by linear regression, and the Bland-Altman test for repeated measurements was
      used to compare bias, precision, and limits of agreement. Changes in lactate
      measurements were evaluated with a four-quadrant plot and trend
      interchangeability method (TIM). Results: In the 23 patients analysed, the
      central venous catheter was used as part of standard care, with no complications.
      The correlation coefficient for absolute values ( n =104) was 0.96 ( P <0.0001).
      The bias, precision, and limits of agreement were -0.19, 0.51, and -1.20 to 0.82
      mmol litre -1 , respectively. The concordance rate for changes in blood lactate
      measurements ( n =80) was 94% with the four-quadrant plot. In contrast, the TIM
      showed that 23 (29) changes in lactate measurements were not interpretable, and
      among the remaining 57 (71) interpretable changes, 18 (32) were interchangeable,
      8 (14) were in the grey zone, and 31 (54) were not interchangeable. Conclusions:
      Microdialysis with a central venous catheter appears to provide reliable absolute
      blood lactate values. Although changes in blood lactate measurements showed an
      excellent concordance rate, changes between the two methods were poorly
      interchangeable with the TIM. Clinical trial registration: NCT02296593.

PMID- 29028911
TI  - Genome-wide pre-miRNA discovery from few labeled examples.
AB  - Motivation: Although many machine learning techniques have been proposed for
      distinguishing miRNA hairpins from other stem-loop sequences, most of the current
      methods use supervised learning, which requires a very good set of positive and
      negative examples. Those methods have important practical limitations when they
      have to be applied to a real prediction task. First, there is the challenge of
      dealing with a scarce number of positive (well-known) pre-miRNA examples.
      Secondly, it is very difficult to build a good set of negative examples for
      representing the full spectrum of non-miRNA sequences. Thirdly, in any genome,
      there is a huge class imbalance (1: 10 000) that is well-known for particularly
      affecting supervised classifiers. Results: To enable efficient and speedy genome
      wide predictions of novel miRNAs, we present miRNAss, which is a novel method
      based on semi-supervised learning. It takes advantage of the information provided
      by the unlabeled stem-loops, thereby improving the prediction rates, even when
      the number of labeled examples is low and not representative of the classes. An
      automatic method for searching negative examples to initialize the algorithm is
      also proposed so as to spare the user this difficult task. MiRNAss obtained
      better prediction rates and shorter execution times than state-of-the-art
      supervised methods. It was validated with genome-wide data from three model
      species, with more than one million of hairpin sequences each, thereby
      demonstrating its applicability to a real prediction task. Availability and
      implementation: An R package can be downloaded from https://cran.r
      project.org/package=miRNAss. In addition, a web-demo for testing the algorithm is
      available at http://fich.unl.edu.ar/sinc/web-demo/mirnass. All the datasets that
      were used in this study and the sets of predicted pre-miRNA are available on
      http://sourceforge.net/projects/sourcesinc/files/mirnass. Contact:
      cyones@sinc.unl.edu.ar. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29028912
TI  - Evidence-based medicine: the clue is in the name.

PMID- 29028913
TI  - Does variable training lead to variable care?

PMID- 29028914
TI  - Trajectory of Total Cholesterol in the Last Years of Life Over Age 80 Years:
      Cohort Study of 99,758 Participants.
AB  - Background: Epidemiological studies suggest that lower total cholesterol (TC) may
      be associated with higher mortality. This study aimed to evaluate whether a
      decline in TC before death might account for the association of TC with mortality
      over age 80 years. Methods: Cohort study using primary care electronic health
      records of 99,758 participants aged 80-105 years from the UK Clinical Practice
      Research Datalink. Hazard ratios for all-cause mortality were adjusted for age,
      gender, frailty, comorbidity, blood pressure, and smoking. Fractional polynomial
      models were fitted to evaluate longitudinal trends in TC before death or end-of
      study. Adjusted odds ratios were estimated using generalized estimating
      equations. Results: There were 63,630 women and 36,128 men, mean age 86 years,
      with 29,200 deaths. There were 41,164 treated with statins at cohort entry.
      Compared with TC values of 4.5-5.4 mmol/L, TC values <3.0 mmol/L were associated
      with higher mortality (statin treated hazard ratios 1.53, 95% confidence interval
      1.43-1.64, p < .001; not treated, 1.41, 1.29-1.54, p < .001). A secular decline
      in TC values accelerated in the last 2 years of life. In the last quarter of
      follow-up, the adjusted odds of TC < 3.0 mmol/L for those who died, compared with
      surviving participants, were 3.33 (2.84-3.91, p < .001) for untreated and 1.88
      (1.68-2.11, p < .001) for statin-treated participants. Conclusions: TC values
      show a terminal decline in the last years of life. Reverse causation may
      contribute to the association of lower TC with higher mortality in nonrandomized
      studies.

PMID- 29028915
TI  - Point-of-care paediatric gastric sonography: can antral cut-off values be used to
      diagnose an empty stomach?
AB  - Background: Gastric sonography is emerging as a valuable clinical point-of-care
      tool to assess aspiration risk. A recent study proposed that a single cut-off
      cross-sectional area (CSA) in the supine position could diagnose an empty stomach
      in the parturient. This study establishes the sensitivity and specificity of a
      single CSA cut-off measurement in both supine and right lateral decubitus (RLD)
      positions in the diagnosis of an empty antrum in paediatric patients. Methods:
      Following induction of anaesthesia, antral sonography was performed in supine and
      RLD positions in 100 fasted paediatric patients prior to upper endoscopic
      evaluation. Following upper endoscopy, any residual stomach content was suctioned
      under direct visualization and antral sonography was immediately performed.
      Antral CSA values were compared using Wilcoxon signed rank test. Receiver
      operator characteristic (ROC) curves were plotted to estimate the discriminating
      power of antral sonography position in the diagnosis of an empty antrum. Results:
      Significant differences were found between pre-suctioned and post-suctioned CSA
      values in the RLD position. The cut-off CSAs of the empty antrum in the supine
      and RLD positions were 2.19 cm2 (sensitivity 75%, specificity 36%) and 3.07 cm2
      (sensitivity 76%, specificity 67%), respectively. Conclusions: The RLD position
      produces the most sensitive and specific CSA cut-off value where an antral CSA of
      <= 3.07 cm2 in the RLD position presents with acceptable performance in the
      ability to discriminate an empty antrum in paediatric patients over 1 yr of age.
      As age increases, the sensitivity and specificity of this test increases in the
      RLD position.

PMID- 29028916
TI  - Hypertension and cataract surgery under loco-regional anaesthesia: not to be
      ignored?

PMID- 29028917
TI  - Comparative usability of modern anaesthesia ventilators: a human factors study.
AB  - Background: The anaesthesia ventilator represents the key equipment for
      intraoperative respiratory care. Improper operation of this device may threaten a
      patient's health. A self-explanatory interface facilitates handling and decreases
      the risk of operating errors. This study systematically evaluates the usability
      of user interfaces in four modern anaesthesia ventilators. Methods: Twenty naive
      operators were asked to execute 20 tasks on each of four different anaesthesia
      ventilators (Avance CS2TM, GE Healthcare; Flow-iTM, Maquet; and PerseusTM and
      PrimusTM, Drager) in a randomized order. The success of task execution, frequency
      of requests for assistance, and processing times were recorded. During the tasks,
      the operators' visual focus was measured via eye-tracking. Additionally,
      subjective assessments of usability were evaluated by a standardized
      questionnaire. For comparison, six experienced operators undertook the same
      protocol. Results: The overall rate of falsely executed tasks was low. Naive
      operators requested assistance least when using the Perseus (26). Pooled
      processing times were shortest for the Perseus (222 s), followed by the Primus
      (223 s), the Avance (238 s), and the Flow-i (353 s). Task-specific processing
      times differed considerably between the devices. Eye-tracking analyses revealed
      associated interface issues that impeded the operators' performance. Operators
      rated usability best for the Perseus [mean (sd): 67 (17) arbitrary units] and
      worst for the Flow-i [50 (16) arbitrary units]. Results from experienced
      operators support these findings by trend. Conclusions: The usability of modern
      anaesthesia ventilators differs considerably. Interface issues of specific tasks
      impair the operator's efficiency. Eliminating the specific usability issues might
      improve the operator's performance and, as a consequence, the patient's safety.

PMID- 29028918
TI  - Is science the answer?

PMID- 29028919
TI  - Physical Activity Producing Low, but Not Medium or Higher, Vertical Impacts Is
      Inversely Related to BMI in Older Adults: Findings From a Multicohort Study.
AB  - Background: High impact physical activity (PA) is thought to improve skeletal
      health, but its relation to other health outcomes are unclear. We investigated
      associations between PA impact magnitude and body mass index (BMI) in older
      adults. Methods: Data were taken from the Cohort for Skeletal Health in Bristol
      and Avon (COSHIBA), Hertfordshire Cohort Study, and MRC National Survey of Health
      and Development. Vertical acceleration peaks from 7-day hip-worn accelerometer
      recordings were used to classify PA as low (0.5 < g < 1.0g), medium (1 < g <
      1.5g), or higher (>=1.5g) impact. Cohort-specific associations of low, medium,
      and higher impact PA with BMI were examined using linear regressions and
      estimates combined using random-effects meta-analysis. Results: A total of 1182
      participants (mean age = 72.7 years, 68% female) were included. Low, medium, and
      higher impact PA were inversely related to BMI in initial models. After
      adjustment for confounders and other impacts, low, but not medium or higher,
      impacts were inversely related to BMI (-0.31, p < .001: overall combined standard
      deviation change in BMI per doubling in the number of low impacts). In adjusted
      analyses of body composition measured by dual-energy X-ray absorptiometry in
      COSHIBA, low, but not medium or higher, impacts were inversely related to total
      body fat mass (-0.19, p < .001) and android:gynoid fat mass ratio (-0.16, p =
      .01), whereas high impact PA was weakly and positively associated with lean mass
      (0.05, p = .06). Conclusions: Greater exposure to PA producing low magnitude
      vertical impacts was associated with lower BMI and fat mass at older age. Low
      impact PA may help reduce obesity risk in older adults.

PMID- 29028920
TI  - Perceived Fatigability and Objective Physical Activity in Mid- to Late-Life.
AB  - Background: Fatigability, defined as fatigue in relation to a standardized task,
      predicts functional decline in older adults independent of reported tiredness or
      energy level. Although the sensation of fatigue, tiredness, and energy level
      adversely affect physical activity (PA), the association between fatigability and
      objectively measured PA is unknown. Methods: Participants in the Baltimore
      Longitudinal Study of Aging (n = 557, 50% women, aged 50-97 years) were
      instructed to wear an Actiheart accelerometer for 7 consecutive days in the free
      living environment. Perceived fatigability was assessed using the Borg rating of
      perceived exertion (RPE) after 5 minutes of treadmill walking at 1.5 mph (0.67
      m/s) and categorized as low (6-7 RPE), intermediate (8-9 RPE), and high (10+ RPE)
      fatigability. Time-of-day PA differences between fatigability groups were
      assessed using mixed-effects modeling. Results: Total daily PA was 1.3% lower for
      every unit increment in perceived fatigability after adjusting for demographic,
      behavioral, and medical factors (p = .01). In time-of-day analyses, the high
      fatigability group was less active compared to the low fatigability group
      throughout the day (8:00 am to 8:00 pm) and the intermediate fatigability group
      in the morning (8:00 am to 12:00 pm). Patterns of PA within the high fatigability
      group differed from both the intermediate and low groups in the morning but
      mirrored the intermediate group in the afternoon and evening. Discussion: These
      results suggest that RPE is a bio-marker of fatigability associated with
      progressively lower PA with aging. Whether the effects of fatigability occurring
      at the end of the day reflect waning energy levels or a voluntary choice that
      could be modified remains to be evaluated.

PMID- 29028921
TI  - SmartPilot(r) view-guided anaesthesia improves postoperative outcomes in hip
      fracture surgery: a randomized blinded controlled study.
AB  - Background: Both under-dosage and over-dosage of general anaesthetics can harm
      frail patients. We hypothesised that computer-assisted anaesthesia using
      pharmacokinetic/pharmacodynamic models guided by SmartPilot(r) View (SPV)
      software could optimise depth of anaesthesia and improve outcomes in patients
      undergoing hip fracture surgery. Methods: This prospective, randomized, single
      centre, blinded trial included patients undergoing hip fracture surgery under
      general anaesthesia. In the intervention group, anaesthesia was guided using SPV
      with predefined targets. In the control group, anaesthesia was delivered by usual
      practice using the same agents (propofol, sufentanil and desflurane). The primary
      endpoint was the time spent in the "appropriate anaesthesia zone" defined as
      bispectral index (BIS) (blinded to the anaesthetist during surgery) of 45-60 and
      systolic arterial pressure of 80-140 mm Hg. Postoperative complications were
      recorded for one month in a blinded manner. Results: Of 100 subjects randomised,
      97 were analysed (n=47 in SPV and 50 in control group). Anaesthetic drug
      consumption was reduced in the SPV group (for propofol and desflurane).
      Intraoperative duration of low BIS (<45) was similar, but cumulative time of low
      systolic arterial pressure (<80 mm Hg) was significantly shorter in the SPV group
      (median (Q1-Q3); 3 (0-40) vs 5 (0-116) min, P=0.013). SPV subjects experienced
      fewer moderate or major postoperative complications at 30-days (8 (17)% vs 18
      (36)%, P=0.035) and shorter length of hospitalisation (8 (2-20) vs 8 (2-60) days,
      P=0.017). Conclusions: SmartPilot(r) View-guided anaesthesia reduces
      intraoperative hypotension duration, occurrence of postoperative complications
      and length of stay in hip fracture surgery patients. Clinical trial registration:
      NCT 02556658.

PMID- 29028922
TI  - Methods for handling longitudinal outcome processes truncated by dropout and
      death.
AB  - Cohort data are often incomplete because some subjects drop out of the study, and
      inverse probability weighting (IPW), multiple imputation (MI), and linear
      increments (LI) are methods that deal with such missing data. In cohort studies
      of ageing, missing data can arise from dropout or death. Methods that do not
      distinguish between these reasons for missingness typically provide inference
      about a hypothetical cohort where no one can die (immortal cohort). It has been
      suggested that inference about the cohort composed of those who are still alive
      at any time point (partly conditional inference) may be more meaningful. MI, LI,
      and IPW can all be adapted to provide partly conditional inference. In this
      article, we clarify and compare the assumptions required by these MI, LI, and IPW
      methods for partly conditional inference on continuous outcomes. We also propose
      augmented IPW estimators for making partly conditional inference. These are more
      efficient than IPW estimators and more robust to model misspecification. Our
      simulation studies show that the methods give approximately unbiased estimates of
      partly conditional estimands when their assumptions are met, but may be biased
      otherwise. We illustrate the application of the missing data methods using data
      from the 'Origins of Variance in the Old-old' Twin study.

PMID- 29028923
TI  - Detecting presence of mutational signatures in cancer with confidence.
AB  - Motivation: Cancers arise as the result of somatically acquired changes in the
      DNA of cancer cells. However, in addition to the mutations that confer a growth
      advantage, cancer genomes accumulate a large number of somatic mutations
      resulting from normal DNA damage and repair processes as well as carcinogenic
      exposures or cancer related aberrations of DNA maintenance machinery. These
      mutagenic processes often produce characteristic mutational patterns called
      mutational signatures. The decomposition of a cancer genome's mutation catalog
      into mutations consistent with such signatures can provide valuable information
      about cancer etiology. However, the results from different decomposition methods
      are not always consistent. Hence, one needs to be able to not only decompose a
      patient's mutational profile into signatures but also establish the accuracy of
      such decomposition. Results: We proposed two complementary ways of measuring
      confidence and stability of decomposition results and applied them to analyze
      mutational signatures in breast cancer genomes. We identified both very stable
      and highly unstable signatures, as well as signatures that previously have not
      been associated with breast cancer. We also provided additional support for the
      novel signatures. Our results emphasize the importance of assessing the
      confidence and stability of inferred signature contributions. Availability: All
      tools developed in this paper have been implemented in an R package, called
      SignatureEstimation, which is available from
      https://www.ncbi.nlm.nih.gov/CBBresearch/Przytycka/index.cgi#signatureestimation.
      Contact: wojtowda@ncbi.nlm.nih.gov (D.W.), przytyck@ncbi.nlm.nih.gov (T.M.P.).
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29028924
TI  - Survivor bias in Mendelian randomization analysis.
AB  - Mendelian randomization studies employ genotypes as experimental handles to infer
      the effect of genetically modified exposures (e.g. vitamin D exposure) on disease
      outcomes (e.g. mortality). The statistical analysis of these studies makes use of
      the standard instrumental variables framework. Many of these studies focus on
      elderly populations, thereby ignoring the problem of left truncation, which
      arises due to the selection of study participants being conditional upon
      surviving up to the time of study onset. Such selection, in general, invalidates
      the assumptions on which the instrumental variables analysis rests. We show that
      Mendelian randomization studies of adult or elderly populations will therefore,
      in general, return biased estimates of the exposure effect when the considered
      genotype affects mortality; in contrast, standard tests of the causal null
      hypothesis that the exposure does not affect the mortality rate remain unbiased,
      even when they ignore this problem of left truncation. To eliminate "survivor
      bias" or "truncation bias" from the effect of exposure on mortality, we next
      propose various simple strategies under a semi-parametric additive hazard model.
      We examine the performance of the proposed methods in simulation studies and use
      them to infer the effect of vitamin D on all-cause mortality based on the
      Monica10 study with the genetic variant filaggrin as instrumental variable.

PMID- 29028925
TI  - Influence of Bayesian optimization on the performance of propofol target
      controlled infusion.
AB  - Background: Target controlled infusion (TCI) systems use population-based
      pharmacokinetic (PK) models that do not take into account inter-individual
      residual variation. This study compares the bias and inaccuracy of a population
      based vs a personalized TCI propofol titration using Bayesian adaptation.
      Haemodynamic and hypnotic stability, and the prediction probability of
      alternative PK models, was studied. Methods: A double-blinded, prospective
      randomized controlled trial of 120 subjects undergoing cardiac surgery was
      conducted. Blood samples were obtained at 10, 35, 50, 65, 75 and 120 min and
      analysed using a point-of-care propofol blood analyser. Bayesian adaptation of
      the PK model was applied at 60 min in the intervention group. Median (Absolute)
      Performance Error (Md(A)PE) was used to evaluate the difference between bias and
      inaccuracy of the models. Haemodynamic (mean arterial pressure [MAP], heart rate)
      and hypnotic (bispectral index [BIS]) stability was studied. The predictive
      performance of four alternative propofol PK models was studied. Results: MdPE and
      MdAPE did not differ between groups during the pre-adjustment period (control
      group: 6.3% and 16%; intervention group: 5.4% and 18%). MdPE differed in the post
      adjustment period (12% vs. -0.3%), but MdAPE did not (18% vs. 15%). No difference
      in heart rate, MAP or BIS was found. Compared with the other models, the Eleveld
      propofol PK model (patients) showed the best prediction performance. Conclusions:
      When an accurate population-based PK model was used for propofol TCI, Bayesian
      adaption of the model improved bias but not precision. Clinical trial
      registration: Dutch Trial Registry NTR4518.

PMID- 29028926
TI  - Structure-based prediction of protein- peptide binding regions using Random
      Forest.
AB  - Motivation: Protein-peptide interactions are one of the most important biological
      interactions and play crucial role in many diseases including cancer. Therefore,
      knowledge of these interactions provides invaluable insights into all cellular
      processes, functional mechanisms, and drug discovery. Protein-peptide
      interactions can be analyzed by studying the structures of protein-peptide
      complexes. However, only a small portion has known complex structures and
      experimental determination of protein-peptide interaction is costly and
      inefficient. Thus, predicting peptide-binding sites computationally will be
      useful to improve efficiency and cost effectiveness of experimental studies.
      Here, we established a machine learning method called SPRINT-Str (Structure-based
      prediction of protein-Peptide Residue-level Interaction) to use structural
      information for predicting protein-peptide binding residues. These predicted
      binding residues are then employed to infer the peptide-binding site by a
      clustering algorithm. Results: SPRINT-Str achieves robust and consistent results
      for prediction of protein-peptide binding regions in terms of residues and sites.
      Matthews' Correlation Coefficient (MCC) for 10-fold cross validation and
      independent test set are 0.27 and 0.293, respectively, as well as 0.775 and
      0.782, respectively for area under the curve. The prediction outperforms other
      state-of-the-art methods, including our previously developed sequence-based
      method. A further spatial neighbor clustering of predicted binding residues leads
      to prediction of binding sites at 20-116% higher coverage than the next best
      method at all precision levels in the test set. The application of SPRINT-Str to
      protein binding with DNA, RNA and carbohydrate confirms the method's capability
      of separating peptide-binding sites from other functional sites. More
      importantly, similar performance in prediction of binding residues and sites is
      obtained when experimentally determined structures are replaced by unbound
      structures or quality model structures built from homologs, indicating its wide
      applicability. Availability and implementation: http://sparks
      lab.org/server/SPRINT-Str. Contact: yangyd25@mail.sysu.edu.cn. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29028927
TI  - Tumor origin detection with tissue-specific miRNA and DNA methylation markers.
AB  - Motivation: A clear identification of the primary site of tumor is of great
      importance to the next targeted site-specific treatments and could efficiently
      improve patient's overall survival. Even though many classifiers based on gene
      expression had been proposed to predict the tumor primary, only a few studies
      focus on using DNA methylation (DNAm) profiles to develop classifiers, and none
      of them compares the performance of classifiers based on different profiles.
      Results: We introduced novel selection strategies to identify highly tissue
      specific CpG sites and then used the random forest approach to construct the
      classifiers to predict the origin of tumors. We also compared the prediction
      performance by applying similar strategy on miRNA expression profiles. Our
      analysis indicated that these classifiers had an accuracy of 96.05% (Maximum
      Relevance-Maximum-Distance: 90.02-99.99%) or 95.31% (principal component
      analysis: 79.82-99.91%) on independent DNAm datasets, and an overall accuracy of
      91.30% (range 79.33-98.74%) on independent miRNA test sets for predicting tumor
      origin. This suggests that our feature selection methods are very effective to
      identify tissue-specific biomarkers and the classifiers we developed can
      efficiently predict the origin of tumors. We also developed a user-friendly
      webserver that helps users to predict the tumor origin by uploading miRNA
      expression or DNAm profile of their interests. Availability and implementation:
      The webserver, and relative data, code are accessible at
      http://server.malab.cn/MMCOP/. Contact: zouquan@nclab.net or
      a.teschendorff@ucl.ac.uk. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29028928
TI  - Effectiveness of tip rotation in fibreoptic bronchoscopy under different
      experimental conditions: an in vitro crossover study.
AB  - Background: Proper manipulation of fibreoptic bronchoscopes is essential for
      successful tracheal intubation or diagnostic bronchoscopy. Failure of proper
      navigation and rotation of the fibrescope may lead to difficulties in advancing
      the fibrescope and might also be responsible for (unnecessary) difficulties and
      delays in fibreoptic tracheal intubation, with subsequent hypoxaemia. The present
      study, therefore, aimed to assess the effectiveness of tip rotation in flexible
      bronchoscopes in different experimental conditions. Methods: Five differently
      sized pairs of fibrescopes (outer diameters of 2.2, 2.4, 3.5, 4.2, and 5.2 mm)
      were inserted into paediatric airway manikins via an appropriately sized
      laryngeal mask and were turned clockwise or anticlockwise at the fibrescope body
      or cord to 45, 90, and 180 degrees , with the cord held either straight or bent.
      The primary outcome measure was the ratio of rotation measured at the tip over
      the rotation performed with the fibrescope body or cord. Results: Overall, the
      'body' turn was significantly less effective when a bent cord was present (mean
      difference ranging from 29.8% (95% confidence interval 8.8-50.9) to 117.4% (93.6
      141.2). This difference was diminished when the 'cord' turn was performed.
      Smaller fibrescopes, with outer diameters of 2.2 and 2.4 mm, were inferior with
      respect to the transmission of 'body' rotation to the tip. Conclusions: 'Cord'
      turning of the fibrescope appears to be more effective in rotating the tip than a
      turn of the fibrescope 'body' only. Straightening the fibrescope cord and
      combined 'body' and 'cord' turning are recommended.

PMID- 29028929
TI  - Peripheral i.v. analysis (PIVA) of venous waveforms for volume assessment in
      patients undergoing haemodialysis.
AB  - Background: The assessment of intravascular volume status remains a challenge for
      clinicians. Peripheral i.v. analysis (PIVA) is a method for analysing the
      peripheral venous waveform that has been used to monitor volume status. We
      present a proof-of-concept study for evaluating the efficacy of PIVA in detecting
      changes in fluid volume. Methods: We enrolled 37 hospitalized patients undergoing
      haemodialysis (HD) as a controlled model for intravascular volume loss.
      Respiratory rate (F0) and pulse rate (F1) frequencies were measured. PIVA signal
      was obtained by fast Fourier analysis of the venous waveform followed by weighing
      the magnitude of the amplitude of the pulse rate frequency. PIVA was compared
      with peripheral venous pressure and standard monitoring of vital signs. Results:
      Regression analysis showed a linear correlation between volume loss and change in
      the PIVA signal (R2=0.77). Receiver operator curves demonstrated that the PIVA
      signal showed an area under the curve of 0.89 for detection of 20 ml kg-1 change
      in volume. There was no correlation between volume loss and peripheral venous
      pressure, blood pressure or pulse rate. PIVA-derived pulse rate and respiratory
      rate were consistent with similar numbers derived from the bio-impedance and
      electrical signals from the electrocardiogram. Conclusions: PIVA is a minimally
      invasive, novel modality for detecting changes in fluid volume status,
      respiratory rate and pulse rate in spontaneously breathing patients with
      peripheral i.v. cannulas.

PMID- 29028930
TI  - Use of a hand-held digital cognitive aid in simulated crises: the MAX randomized
      controlled trial.
AB  - Background: Cognitive aids improve the technical performance of individuals and
      teams dealing with high-stakes crises. Hand-held electronic cognitive aids have
      rarely been investigated. A randomized controlled trial was conducted to
      investigate the effects of a smartphone application, named MAX (for Medical
      Assistance eXpert), on the technical and non-technical performance of anaesthesia
      residents dealing with simulated crises. Methods: This single-centre randomized,
      controlled, unblinded trial was conducted in the simulation centre at Lyon,
      France. Participants were anaesthesia residents with >1 yr of clinical
      experience. Each participant had to deal with two different simulated crises with
      and without the help of a digital cognitive aid. The primary outcome was
      technical performance, evaluated as adherence to guidelines. Two independent
      observers remotely assessed performance on video recordings. Results: Fifty-two
      residents were included between July 2015 and February 2016. Six participants
      were excluded for technical issues; 46 participants were confronted with a total
      of 92 high-fidelity simulation scenarios (46 with MAX and 46 without). Mean (sd)
      age was 27 (1.8) yr and clinical experience 3.2 (1.0) yr. Inter-rater agreement
      was 0.89 (95% confidence interval 0.85-0.92). Mean technical scores were higher
      when residents used MAX [82 (11.9) vs 59 (10.8)%; P<0.001]. Conclusion: The use
      of a hand-held cognitive aid was associated with better technical performance of
      residents dealing with simulated crises. These findings could help digital
      cognitive aids to find their way into daily medical practice and improve the
      quality of health care when dealing with high-stakes crises. Clinical trial
      registration: NCT02678819.

PMID- 29028932
TI  - Surgical pleth index: prediction of postoperative pain in children?
AB  - Background: Surgical Pleth Index (SPI) is a non-invasive, dimensionless score (0
      100) aimed to allow an estimate of intraoperative nociception. Thus, it may be a
      useful tool to guide intraoperative analgesia. However, no optimum SPI target
      range for the use in children has yet been defined. It was the aim of this study
      to define a clinically appropriate SPI target to predict moderate-severe
      postoperative pain in children. Methods: After ethics approval 105 children (2-16
      yr) undergoing elective sevoflurane/opioid-based anaesthesia were included. SPI
      was recorded directly before the end of surgery and compared with acute
      postoperative pain (age appropriately assessed on different pain scales in the
      age groups two to three yr, four to eight yr and nine to16 yr) in the
      postoperative acute care unit (PACU). Results: Data of 93 children were analysed.
      A significant negative correlation was found between age and SPI (r=-0.43;
      P=0.03). The SPI cut-off value with the highest sensitivity (76%) and specificity
      (62%) in all children combined was 40. The negative predictive value for SPI <=
      40 to predict the absence of moderate-severe pain in PACU was 87.5%. The commonly
      used SPI cut-off (50) published in all related studies had neither any clinically
      relevant sensitivity nor specificity to predict the presence or absence of acute
      pain in PACU. Conclusions: The results suggest that a lower (<= 40) than
      previously published (50) target for SPI may be more appropriate in studies
      investigating SPI guided anaesthesia in children, if the avoidance of moderate
      severe postoperative pain is the main goal. Clinical trial registration:
      ACTRN12616001139460.

PMID- 29028931
TI  - DeepGO: predicting protein functions from sequence and interactions using a deep
      ontology-aware classifier.
AB  - Motivation: A large number of protein sequences are becoming available through
      the application of novel high-throughput sequencing technologies. Experimental
      functional characterization of these proteins is time-consuming and expensive,
      and is often only done rigorously for few selected model organisms. Computational
      function prediction approaches have been suggested to fill this gap. The
      functions of proteins are classified using the Gene Ontology (GO), which contains
      over 40 000 classes. Additionally, proteins have multiple functions, making
      function prediction a large-scale, multi-class, multi-label problem. Results: We
      have developed a novel method to predict protein function from sequence. We use
      deep learning to learn features from protein sequences as well as a cross-species
      protein-protein interaction network. Our approach specifically outputs
      information in the structure of the GO and utilizes the dependencies between GO
      classes as background information to construct a deep learning model. We evaluate
      our method using the standards established by the Computational Assessment of
      Function Annotation (CAFA) and demonstrate a significant improvement over
      baseline methods such as BLAST, in particular for predicting cellular locations.
      Availability and implementation: Web server: http://deepgo.bio2vec.net, Source
      code: https://github.com/bio-ontology-research-group/deepgo. Contact:
      robert.hoehndorf@kaust.edu.sa. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29028933
TI  - Novel method for intraoperative assessment of cerebral autoregulation by paced
      breathing.
AB  - Background: Cerebral autoregulation (CA) is the mechanism that maintains
      constancy of cerebral blood flow (CBF) despite variations in blood pressure (BP).
      Patients with attenuated CA have been shown to have an increased incidence of
      peri-operative stroke. Studies of CA in anaesthetized subjects are rare, because
      a simple and non-invasive method to quantify the integrity of CA is not
      available. In this study, we set out to improve non-invasive quantification of CA
      during surgery. For this purpose, we introduce a novel method to amplify
      spontaneous BP fluctuations during surgery by imposing mechanical positive
      pressure ventilation at three different frequencies and quantify CA from the
      resulting BP oscillations. Methods: Fourteen patients undergoing sevoflurane
      anaesthesia were included in the study. Continuous non-invasive BP and
      transcranial Doppler-derived CBF velocity (CBF V ) were obtained before surgery
      during 3 min of paced breathing at 6, 10, and 15 bpm and during surgery from
      mechanical positive pressure ventilation at identical frequencies. Data were
      analysed using frequency domain analysis to obtain CBF V -to-BP phase lead as a
      continuous measure of CA efficacy. Group averages were calculated. Values are
      means ( sd ), and P <0.05 was used to indicate statistical significance. Results:
      Preoperative vs intraoperative CBF V -to-BP phase lead was 43 (9) vs 45 (8)
      degrees , 25 (8) vs 24 (10) degrees , and 4 (6) vs -2 (12) degrees  during 6, 10,
      and 15 bpm, respectively (all P =NS). Conclusions: During surgery, cerebral
      autoregulation indices were similar to values determined before surgery. This
      indicates that CA can be quantified reliably and non-invasively using this novel
      method and confirms earlier evidence that CA is unaffected by sevoflurane
      anaesthesia. Clinical trial registration: NCT03071432.

PMID- 29028934
TI  - DeepLoc: prediction of protein subcellular localization using deep learning.

PMID- 29028936
TI  - Lost in translation? Comparing the effectiveness of electronic-based and paper
      based cognitive aids.

PMID- 29028937
TI  - Abnormal Structural Brain Connectome in Individuals with Preclinical Alzheimer's
      Disease.
AB  - Alzheimer's disease has a long preclinical phase during which amyloid pathology
      and neurodegeneration accumulate in the brain without producing overt cognitive
      deficits. It is currently unclear whether these early disease stages are
      associated with a progressive disruption in the communication between brain
      regions that subsequently leads to cognitive decline and dementia. In this study
      we assessed the organization of structural networks in cognitively normal (CN)
      individuals harboring amyloid pathology (A+N-), neurodegeneration (A-N+), or both
      (A+N+) from the prospective and longitudinal Swedish BioFINDER study. We combined
      graph theory with diffusion tensor imaging to investigate integration,
      segregation, and centrality measures in the brain connectome in the previous
      groups. At baseline, our findings revealed a disrupted network topology
      characterized by longer paths, lower efficiency, increased clustering and
      modularity in CN A-N+ and CN A+N+, but not in CN A+N-. After 2 years, CN A+N+
      showed significant abnormalities in all global network measures, whereas CN A-N+
      only showed abnormalities in the global efficiency. Network connectivity and
      organization were associated with memory in CN A+N+ individuals. Altogether, our
      findings suggest that amyloid pathology is not sufficient to disrupt structural
      network topology, whereas neurodegeneration is.

PMID- 29028935
TI  - Latent-Profile Analysis Reveals Behavioral and Brain Correlates of Dopamine
      Cognition Associations.
AB  - Evidence suggests that associations between the neurotransmitter dopamine and
      cognition are nonmonotonic and open to modulation by various other factors. The
      functional implications of a given level of dopamine may therefore differ from
      person to person. By applying latent-profile analysis to a large (n = 181) sample
      of adults aged 64-68 years, we probabilistically identified 3 subgroups that
      explain the multivariate associations between dopamine D2/3R availability (probed
      with 11C-raclopride-PET, in cortical, striatal, and hippocampal regions) and
      cognitive performance (episodic memory, working memory, and perceptual speed).
      Generally, greater receptor availability was associated with better cognitive
      performance. However, we discovered a subgroup of individuals for which high
      availability, particularly in striatum, was associated with poor performance,
      especially for working memory. Relative to the rest of the sample, this subgroup
      also had lower education, higher body-mass index, and lower resting-state
      connectivity between caudate nucleus and dorsolateral prefrontal cortex. We
      conclude that a smaller subset of individuals induces a multivariate non-linear
      association between dopamine D2/3R availability and cognitive performance in this
      group of older adults, and discuss potential reasons for these differences that
      await further empirical scrutiny.

PMID- 29028939
TI  - Serotonin 2A Receptor Signaling Underlies LSD-induced Alteration of the Neural
      Response to Dynamic Changes in Music.
AB  - Classic psychedelic drugs (serotonin 2A, or 5HT2A, receptor agonists) have
      notable effects on music listening. In the current report, blood oxygen level
      dependent (BOLD) signal was collected during music listening in 25 healthy adults
      after administration of placebo, lysergic acid diethylamide (LSD), and LSD
      pretreated with the 5HT2A antagonist ketanserin, to investigate the role of 5HT2A
      receptor signaling in the neural response to the time-varying tonal structure of
      music. Tonality-tracking analysis of BOLD data revealed that 5HT2A receptor
      signaling alters the neural response to music in brain regions supporting basic
      and higher-level musical and auditory processing, and areas involved in memory,
      emotion, and self-referential processing. This suggests a critical role of 5HT2A
      receptor signaling in supporting the neural tracking of dynamic tonal structure
      in music, as well as in supporting the associated increases in emotionality,
      connectedness, and meaningfulness in response to music that are commonly observed
      after the administration of LSD and other psychedelics. Together, these findings
      inform the neuropsychopharmacology of music perception and cognition, meaningful
      music listening experiences, and altered perception of music during psychedelic
      experiences.

PMID- 29028938
TI  - Impact of the US Maternal Tetanus, Diphtheria, and Acellular Pertussis
      Vaccination Program on Preventing Pertussis in Infants <2 Months of Age: A Case
      Control Evaluation.
AB  - Background: Infants aged <1 year are at highest risk for pertussis-related
      morbidity and mortality. In 2012, Tdap (tetanus toxoid, reduced diphtheria
      toxoid, and acellular pertussis) vaccine was recommended for women during each
      pregnancy to protect infants in the first months of life; data on effectiveness
      of this strategy are currently limited. Methods: We conducted a case-control
      evaluation among pertussis cases <2 months old with cough onset between 1 January
      2011 and 31 December 2014 from 6 US Emerging Infection Program Network states.
      Controls were hospital-matched and selected by birth certificate. Mothers were
      interviewed to collect information on demographics, household characteristics,
      and healthcare providers. Provider-verified immunization history was obtained on
      mothers and infants. Mothers were considered vaccinated during pregnancy if Tdap
      was received >=14 days before delivery; trimester was calculated using Tdap date,
      infant's date of birth, and gestational age. Odds ratios were calculated using
      multivariable conditional logistic regression; vaccine effectiveness (VE) was
      estimated as (1 - odds ratio) * 100%. Results: A total of 240 cases and 535
      controls were included; 17 (7.1%) case mothers and 90 (16.8%) control mothers
      received Tdap during the third trimester of pregnancy. The multivariable VE
      estimate for Tdap administered during the third trimester of pregnancy was 77.7%
      (95% confidence interval [CI], 48.3%-90.4%); VE increased to 90.5% (95% CI, 65.2%
      97.4%) against hospitalized cases. Conclusions: Vaccination during pregnancy is
      an effective way to protect infants during the early months of life. With a
      continuing resurgence in pertussis, efforts should focus on maximizing Tdap
      uptake among pregnant women.

PMID- 29028940
TI  - Optogenetic Activation of the Sensorimotor Cortex Reveals "Local Inhibitory and
      Global Excitatory" Inputs to the Basal Ganglia.
AB  - To understand how information from different cortical areas is integrated and
      processed through the cortico-basal ganglia pathways, we used optogenetics to
      systematically stimulate the sensorimotor cortex and examined basal ganglia
      activity. We utilized Thy1-ChR2-YFP transgenic mice, in which channelrhodopsin 2
      is robustly expressed in layer V pyramidal neurons. We applied light spots to the
      sensorimotor cortex in a grid pattern and examined neuronal responses in the
      globus pallidus (GP) and entopeduncular nucleus (EPN), which are the relay and
      output nuclei of the basal ganglia, respectively. Light stimulation typically
      induced a triphasic response composed of early excitation, inhibition, and late
      excitation in GP/EPN neurons. Other response patterns lacking 1 or 2 of the
      components were also observed. The distribution of the cortical sites whose
      stimulation induced a triphasic response was confined, whereas stimulation of the
      large surrounding areas induced early and late excitation without inhibition. Our
      results suggest that cortical inputs to the GP/EPN are organized in a "local
      inhibitory and global excitatory" manner. Such organization seems to be the
      neuronal basis for information processing through the cortico-basal ganglia
      pathways, that is, releasing and terminating necessary information at an
      appropriate timing, while simultaneously suppressing other unnecessary
      information.

PMID- 29028941
TI  - Dysregulation of Cortical Neuron DNA Methylation Profile in Autism Spectrum
      Disorder.
AB  - Autism Spectrum Disorder (ASD) is a complex neuropsychiatric syndrome whose
      etiology includes genetic and environmental components. Since epigenetic marks
      are sensitive to environmental insult, they may be involved in the development of
      ASD. Initial brain studies have suggested a dysregulation of epigenetic marks in
      ASD. However, due to cellular heterogeneity in the brain, these studies have not
      determined if there is a true change in the neuronal epigenetic signature. Here,
      we report a genome-wide methylation study on fluorescence-activated cell sorting
      sorted neuronal nuclei from the frontal cortex of 16 male ASD and 15 male control
      subjects. Using the 450 K BeadArray, we identified 58 differentially methylated
      regions (DMRs) that included loci associated to GABAergic system genes,
      particularly ABAT and GABBR1, and brain-specific MicroRNAs. Selected DMRs were
      validated by targeted Next Generation Bisulfite Sequencing. Weighted gene
      correlation network analysis detected 3 co-methylation modules which are
      significantly correlated to ASD that were enriched for genomic regions underlying
      neuronal, GABAergic, and immune system genes. Finally, we determined an overlap
      of the 58 ASD-related DMRs with neurodevelopment associated DMRs. This
      investigation identifies alterations in the DNA methylation pattern in ASD
      cortical neurons, providing further evidence that epigenetic alterations in
      disorder-relevant tissues may be involved in the biology of ASD.

PMID- 29028943
TI  - A joint model for mixed and truncated longitudinal data and survival data, with
      application to HIV vaccine studies.
AB  - In HIV vaccine studies, a major research objective is to identify immune response
      biomarkers measured longitudinally that may be associated with risk of HIV
      infection. This objective can be assessed via joint modeling of longitudinal and
      survival data. Joint models for HIV vaccine data are complicated by the following
      issues: (i) left truncations of some longitudinal data due to lower limits of
      quantification; (ii) mixed types of longitudinal variables; (iii) measurement
      errors and missing values in longitudinal measurements; (iv) computational
      challenges associated with likelihood inference. In this article, we propose a
      joint model of complex longitudinal and survival data and a computationally
      efficient method for approximate likelihood inference to address the foregoing
      issues simultaneously. In particular, our model does not make unverifiable
      distributional assumptions for truncated values, which is different from methods
      commonly used in the literature. The parameters are estimated based on the h
      likelihood method, which is computationally efficient and offers approximate
      likelihood inference. Moreover, we propose a new approach to estimate the
      standard errors of the h-likelihood based parameter estimates by using an
      adaptive Gauss-Hermite method. Simulation studies show that our methods perform
      well and are computationally efficient. A comprehensive data analysis is also
      presented.

PMID- 29028942
TI  - Association of high-evidence gastric cancer susceptibility loci and somatic gene
      expression levels with survival.
AB  - Eleven high-evidence single-nucleotide polymorphisms (SNPs) at nine loci for
      gastric cancer (GC) risk were reported, but their associations with survival
      remain unknown. In this study, we examined associations between SNP and GC
      survival by anatomic location and histology among 1147 incident cases from the
      Shanxi Upper Gastrointestinal Genetics Project. We further examined whether SNPs
      were expression quantitative trait loci in normal and tumor gastric tissues, and
      whether tumor versus normal somatic mRNA differences in 126 cases were associated
      with survival. No SNPs were associated with GC survival overall. However, subtype
      specific associations were observed for gastric cardia adenocarcinomas at
      MUC1/TRIM46/1q22 rs2070803 [HRAA versus GA+GG = 2.16; 95% confidence interval
      (CI) = 1.24-3.78; P = 0.0068] and LTA/TNF/6p21.33 rs1799724 (HRTT+CT versus CC =
      1.30; 95% CI = 1.07-1.57; P = 0.0077), and for diffuse-type GC at PSCA/8q24.3
      rs2294008 (HRTT versus CT+CC = 1.99; 95% CI = 1.33-2.97; P = 7.8E-04). Rs2294008T
      was a cis-expression quantitative trait loci for PSCA, upregulating mRNA in
      normal gastric (beta = 0.60; P = 5.7E-21) and GC (beta = 0.30; P = 0.0089)
      tissues. Cases in the highest quartile (the smallest downregulation of tumor
      PSCA) had shortest survival than cases with the most downregulated PSCA (median
      survival of 0.47 years in the highest quartile versus 3.73 years in the lowest
      quartile; hazard ratio = 9.70; 95% CI = 2.46-38.4; P = 0.0012). Less striking
      effects for mRNA levels were observed for MTX1 at 1q22 in gastric cardia
      adenocarcinoma and for JRK at 8q24.3 in diffuse GC. Our results suggest three
      high-evidence GC risk loci have prognostic importance in GC subtypes. Future
      studies in well-characterized independent populations are warranted to validate
      our findings and further investigate the clinical utility of these variants in
      predicting GC prognosis.

PMID- 29028946
TI  - Mouse Cntnap2 and Human CNTNAP2 ASD Alleles Cell Autonomously Regulate PV+
      Cortical Interneurons.
AB  - Human mutations in CNTNAP2 are associated with an array of neuropsychiatric and
      neurological syndromes, including speech and language disorders, epilepsy, and
      autism spectrum disorder (ASD). We examined Cntnap2's expression and function in
      GABAergic cortical interneurons (CINs), where its RNA is present at highest
      levels in chandelier neurons, PV+ neurons and VIP+ neurons. In vivo functions
      were studied using both constitutive Cntnap2 null mice and a transplantation
      assay, the latter to assess cell autonomous phenotypes of medial ganglionic
      eminence (MGE)-derived CINs. We found that Cntnap2 constitutive null mutants had
      normal numbers of MGE-derived CINs, but had reduced PV+ CINs. Transplantation
      assays showed that Cntnap2 cell autonomously regulated the physiology of
      parvalbumin (PV)+, fast-spiking CINs; no phenotypes were observed in
      somatostatin+, regular spiking, CINs. We also tested the effects of 4 human
      CNTNAP2 ASD missense mutations in vivo, and found that they impaired PV+ CIN
      development. Together, these data reveal that reduced CNTNAP2 function impairs
      PV+ CINs, a cell type with important roles in regulating cortical circuits.

PMID- 29028944
TI  - Identification and replication of the interplay of four genetic high-risk
      variants for urinary bladder cancer.
AB  - Little is known whether genetic variants identified in genome-wide association
      studies interact to increase bladder cancer risk. Recently, we identified two-
      and three-variant combinations associated with a particular increase of bladder
      cancer risk in a urinary bladder cancer case-control series (Leibniz Research
      Centre for Working Environment and Human Factors at TU Dortmund (IfADo), 1501
      cases, 1565 controls). In an independent case-control series (Nijmegen Bladder
      Cancer Study, NBCS, 1468 cases, 1720 controls) we confirmed these two- and three
      variant combinations. Pooled analysis of the two studies as discovery group
      (IfADo-NBCS) resulted in sufficient statistical power to test up to four-variant
      combinations by a logistic regression approach. The New England and Spanish
      Bladder Cancer Studies (2080 cases and 2167 controls) were used as a replication
      series. Twelve previously identified risk variants were considered. The strongest
      four-variant combination was obtained in never smokers. The combination of
      rs1014971[AA] near apolipoprotein B mRNA editing enzyme, catalytic polypeptide
      like 3A (APOBEC3A) and chromobox homolog 6 (CBX6), solute carrier family 1s4
      (urea transporter), member 1 (Kidd blood group) (SLC14A1) exon single nucleotide
      polymorphism (SNP) rs1058396[AG, GG], UDP glucuronosyltransferase 1 family,
      polypeptide A complex locus (UGT1A) intron SNP rs11892031[AA] and rs8102137[CC,
      CT] near cyclin E1 (CCNE1) resulted in an unadjusted odds ratio (OR) of 2.59 (95%
      CI = 1.93-3.47; P = 1.87 * 10-10), while the individual variant ORs ranged only
      between 1.11 and 1.30. The combination replicated in the New England and Spanish
      Bladder Cancer Studies (ORunadjusted = 1.60, 95% CI = 1.10-2.33; P = 0.013). The
      four-variant combination is relatively frequent, with 25% in never smoking cases
      and 11% in never smoking controls (total study group: 19% cases, 14% controls).
      In conclusion, we show that four high-risk variants can statistically interact to
      confer increased bladder cancer risk particularly in never smokers.

PMID- 29028945
TI  - Sphingosine Kinase 1 expression in peritoneal macrophages is required for colon
      carcinogenesis.
AB  - Accumulating evidence suggests that the sphingosine kinase 1 (SphK1)/sphingosine
      1-phosphate (S1P) pathway plays a pivotal role in colon carcinogenesis. Our
      previous studies indicate that the SphK1/S1P pathway mediates colon
      carcinogenesis at least by regulating cyclooxygenase 2 (COX-2) expression and
      prostaglandin E2 (PGE2) production. However, the mechanisms by which this pathway
      regulates colon carcinogenesis are still unclear. First, we show that SphK1
      deficient mice significantly attenuated azoxymethane (AOM)-induced colon
      carcinogenesis as measured by colon tumor incidence, multiplicity, and volume. We
      found that AOM activates peritoneal macrophages to induce SphK1, COX-2, and tumor
      necrosis factor (TNF)-alpha expression in WT mice. Interestingly, SphK1 knockout
      (KO) mice revealed significant reduction of COX-2 and TNF-alpha expression from
      AOM-activated peritoneal macrophages, suggesting that SphK1 regulates COX-2 and
      TNF-alpha expression in peritoneal macrophages. We found that inoculation of WT
      peritoneal macrophages restored the carcinogenic effect of AOM in Sphk1 KO mice
      as measured by aberrant crypt foci (ACF) formation, preneoplastic lesions of
      colon cancer. In addition, downregulation of SphK1 only in peritoneal macrophage
      by short hairpin RNA (shRNA) reduced the number of ACF per colon induced by AOM.
      Intraperitoneal injection of sphingolipids demonstrates that S1P enhanced AOM
      induced ACF formation, while ceramide inhibited. Finally, we show that SphK
      inhibitor SKI-II significantly reduced the number of ACF per colon. These results
      suggest that SphK1 expression plays a pivotal role in the early stages of colon
      carcinogenesis through regulating COX-2 and TNF-alpha expression from activated
      peritoneal macrophages.

PMID- 29028948
TI  - Volumes of the spinal canal and caudal space in children zero to three years of
      age assessed by magnetic resonance imaging: implications for volume dosage of
      caudal blockade.
AB  - Background: The primary aim of this study was to objectively assess the different
      spinal and caudal volumes that are of interest for caudal block volume dosing.
      Methods: Three directly assessed (volume of spinal canal/caudal space, volume of
      the dural sac and volume of spinal cord) and two derived volumes (volume of the
      epidural space and cerebrospinal fluid volume) were determined from magnetic
      resonance images (MRI) in 20 children (zero - three yr of age). The assessed
      volumes were correlated to age, height and weight. Furthermore, the volumes of
      the epidural space from caudal canal to three different clinically relevant
      target levels (L 1, Th 10 and Th 6) and the epidural volume of each individual
      spinal segment at the caudal, lumbar and thoracic levels were calculated.
      Results: All volumes correlated in a linear manner to length and weight (R2 0.614
      - 0.867) whereas a curvilinear correlation was associated with best curve fit for
      age (R2 0.696 - 0.883). The median volumes of the epidural space from caudal
      canal to L 1, Th 10 and Th 6 were 1.30 ml kg-1 (95%CI 1.08-1.51), 1.57 ml kg-1
      (95%CI 1.29-1.81) and 1.78 ml kg-1 (95%CI 1.52-2.08), respectively. The median
      volumes of the epidural space per vertebral segment were Thoracic: 0.60 ml (95%CI
      0.38-0.75); Lumbar: 1.18 ml (95%CI 0.94-1.43) and Caudal: 0.85 ml (95%CI 0.56
      1.18). Conclusions: The spinal volumes of interest show a linear correlation to
      height and weight whereas a curvilinear correlation was found for age. The volume
      of the epidural space per segment was found to be significantly higher at the
      lumbar level compared with the caudal and thoracic levels.

PMID- 29028947
TI  - Dlx1 and Dlx2 Promote Interneuron GABA Synthesis, Synaptogenesis, and
      Dendritogenesis.
AB  - The postnatal functions of the Dlx1&2 transcription factors in cortical
      interneurons (CINs) are unknown. Here, using conditional Dlx1, Dlx2, and Dlx1&2
      knockouts (CKOs), we defined their roles in specific CINs. The CKOs had
      dendritic, synaptic, and survival defects, affecting even PV+ CINs. We provide
      evidence that DLX2 directly drives Gad1, Gad2, and Vgat expression, and show that
      mutants had reduced mIPSC amplitude. In addition, the mutants formed fewer
      GABAergic synapses on excitatory neurons and had reduced mIPSC frequency.
      Furthermore, Dlx1/2 CKO had hypoplastic dendrites, fewer excitatory synapses, and
      reduced excitatory input. We provide evidence that some of these phenotypes were
      due to reduced expression of GRIN2B (a subunit of the NMDA receptor), a high
      confidence Autism gene. Thus, Dlx1&2 coordinate key components of CIN postnatal
      development by promoting their excitability, inhibitory output, and survival.

PMID- 29028949
TI  - Pyramidal Cell Subtypes and Their Synaptic Connections in Layer 5 of Rat Frontal
      Cortex.
AB  - The frontal cortical areas make a coordinated response that generates appropriate
      behavior commands, using individual local circuits with corticostriatal and
      corticocortical connections in longer time scales than sensory areas. In
      secondary motor cortex (M2), situated between the prefrontal and primary motor
      areas, major subtypes of layer 5 corticostriatal cells are crossed
      corticostriatal (CCS) cells innervating both sides of striatum, and
      corticopontine (CPn) cells projecting to the ipsilateral striatum and pontine
      nuclei. CCS cells innervate CPn cells unidirectionally: the former are therefore
      hierarchically higher than the latter among L5 corticostriatal cells. CCS cells
      project directly to both frontal and nonfrontal areas. On the other hand, CPn
      cells innervate the thalamus and layer 1a of frontal areas, where thalamic fibers
      relaying basal ganglia outputs are distributed. Thus, CCS cells can make
      activities of frontal areas in concert with those of nonfrontal area using
      corticocortical loops, whereas CPn cells are more involved in closed
      corticostriatal loops than CCS cells. Since reciprocal connections between CPn
      cells with facilitatory synapses may be related to persistent activity, CPn cells
      play a key role of longer time constant processes in corticostriatal as well as
      in corticocortical loops between the frontal areas.

PMID- 29028951
TI  - Big data, small airways, big problems.

PMID- 29028950
TI  - Epidemiology and Relative Severity of Influenza Subtypes in Singapore in the Post
      Pandemic Period from 2009 to 2010.
AB  - Background: After 2009, pandemic influenza A(H1N1) [A(H1N1)pdm09] cocirculated
      with A(H3N2) and B in Singapore. Methods: A cohort of 760 participants
      contributed demographic data and up to 4 blood samples each from October 2009 to
      September 2010. We compared epidemiology of the 3 subtypes and investigated
      evidence for heterotypic immunity through multivariable logistic regression using
      a generalized estimating equation. To examine age-related differences in severity
      between subtypes, we used LOESS (locally weighted smoothing) plots of
      hospitalization to infection ratios and explored birth cohort effects referencing
      the pandemic years (1957; 1968). Results: Having more household members aged 5-19
      years and frequent public transport use increased risk of infection, while
      preexisting antibodies against the same subtype (odds ratio [OR], 0.61; P = .002)
      and previous influenza infection against heterotypic infections (OR, 0.32; P =
      .045) were protective. A(H1N1)pdm09 severity peaked in those born around 1957,
      while A(H3N2) severity was least in the youngest individuals and increased until
      it surpassed A(H1N1)pdm09 in those born in 1952 or earlier. Further analysis
      showed that severity of A(H1N1)pdm09 was less than that for A(H3N2) in those born
      in 1956 or earlier (P = .021) and vice versa for those born in 1968 or later (P <
      .001), with no difference in those born between 1957 and 1967 (P = .632).
      Conclusions: Our findings suggest that childhood exposures had long-term impact
      on immune responses consistent with the theory of antigenic sin. This, plus
      observations on short-term cross-protection, have implications for vaccination
      and influenza epidemic and pandemic mitigation strategies.

PMID- 29028952
TI  - The efficacy of GlideScope(r) videolaryngoscopy compared with direct laryngoscopy
      in children who are difficult to intubate: an analysis from the paediatric
      difficult intubation registry.
AB  - Background: We analysed data from the Paediatric Difficult Intubation Registry
      examining the use of direct laryngoscopy and GlideScope(r) videolaryngoscopy.
      Methods: Data collected by a multicentre, paediatric difficult intubation
      registry from 1295 patients were analysed. Rates of success and complications
      between direct laryngoscopy and GlideScope videolaryngoscopy were analysed.
      Results: Initial (464/877 = 53% vs 33/828 = 4%, Z-test = 22.2, P < 0.001) and
      eventual (720/877 = 82% vs. 174/828 = 21%, Z-test = 25.2, P < 0.001) success
      rates for GlideScope were significantly higher than direct laryngoscopy. Children
      weighing <10 kg had lower success rates with the GlideScope than the group as a
      whole. There were no differences in complication rates per attempt between direct
      laryngoscopy and GlideScope. The direct laryngoscopy group had more complications
      associated with the greater number of attempts needed to intubate. There were no
      increased risks of hypoxia or trauma with GlideScope use. Each additional attempt
      at intubation with either device resulted in a two-fold increase in complications
      (odds ratio: 2.0, 95% confidence interval: 1.5-2.5, P < 0.001). Conclusions:
      During difficult tracheal intubation in children, direct laryngoscopy is an
      overly used technique with a low chance of success. GlideScope use was associated
      with a higher chance of success with no increased risk of complications.
      GlideScope use in children with difficult tracheal intubation has a lower success
      rate than in adults with difficult tracheal intubation. Children weighing less
      than 10 kilograms had lower success rates with either device. Attempts should be
      minimized with either device to decrease complications.

PMID- 29028953
TI  - Overutilization of Antibiotics in Children With Diarrhea: First Do No Harm.

PMID- 29028955
TI  - Gamma-Band Oscillations Preferential for Nociception can be Recorded in the Human
      Insula.
AB  - Transient nociceptive stimuli elicit robust phase-locked local field potentials
      (LFPs) in the human insula. However, these responses are not preferential for
      nociception, as they are also elicited by transient non-nociceptive vibrotactile,
      auditory, and visual stimuli. Here, we investigated whether another feature of
      insular activity, namely gamma-band oscillations (GBOs), is preferentially
      observed in response to nociceptive stimuli. Although nociception-evoked GBOs
      have never been explored in the insula, previous scalp electroencephalography and
      magnetoencephalography studies suggest that nociceptive stimuli elicit GBOs in
      other areas such as the primary somatosensory and prefrontal cortices, and that
      this activity could be closely related to pain perception. Furthermore, tracing
      studies showed that the insula is a primary target of spinothalamic input. Using
      depth electrodes implanted in 9 patients investigated for epilepsy, we acquired
      insular responses to brief thermonociceptive stimuli and similarly arousing non
      nociceptive vibrotactile, auditory, and visual stimuli (59 insular sites). As
      compared with non-nociceptive stimuli, nociceptive stimuli elicited a markedly
      stronger enhancement of GBOs (150-300 ms poststimulus) at all insular sites,
      suggesting that this feature of insular activity is preferential for
      thermonociception. Although this activity was also present in temporal and
      frontal regions, its magnitude was significantly greater in the insula as
      compared with these other regions.

PMID- 29028956
TI  - Age Differences in the Neural Mechanisms of Intertemporal Choice Under Subjective
      Decision Conflict.
AB  - Older decision-makers may capitalize on their greater experiences in financial
      decisions and by this offset decline in cognitive abilities. However, this
      pattern of results should reverse in situations that place high demands on
      cognitive control functions. In this study, we investigated how decision conflict
      affects the neural mechanisms of intertemporal decision-making in younger and
      older adults. To individually adjust the level of decision conflict we determined
      the indifference point (IDP) in intertemporal decision-making for each
      participant. During functional magnetic resonance imaging, participants performed
      choice options close to their IDP (high conflict) or far away from the IDP (low
      conflict). In younger adults, decision conflict leads to reduced delay
      discounting and lower discount rates are associated with higher working memory
      (WM) capacity. In older adults, high decision conflict is associated with
      enhanced discounting, hypoactivation in the ventral striatum as well diminished
      ventral striatal representations of differences in subjective values. Taken
      together, our results show that under enhanced decision conflict, younger adults
      engage in a more reflective decision mode that reflects individual differences in
      WM capacity. In contrast, older adults get more present-oriented under high
      demands on cognitive control and this decision bias is associated with changes in
      striatal value signaling.

PMID- 29028954
TI  - 1-Benzyl-indole-3-carbinol is a highly potent new small molecule inhibitor of
      Wnt/beta-catenin signaling in melanoma cells that coordinately inhibits cell
      proliferation and disrupts expression of microphthalmia-associated transcription
      factor isoform-M.
AB  - 1-Benzyl-indole-3-carbinol (1-benzyl-I3C), a synthetic analogue of the crucifer
      derived natural phytochemical I3C, displayed significantly wider sensitivity and
      anti-proliferative potency in melanoma cells than the natural compound. Unlike
      I3C, which targets mainly oncogenic BRAF-expressing cells, 1-benzyl-I3C
      effectively inhibited proliferation of melanoma cells with a more extensive range
      of mutational profiles, including those expressing wild-type BRAF. In both
      cultured melanoma cell lines and in vivo in melanoma cell-derived tumor
      xenografts, 1-benzyl-I3C disrupted canonical Wnt/beta-catenin signaling that
      resulted in the downregulation of beta-catenin protein levels with a concomitant
      increase in levels of the beta-catenin destruction complex components such as
      glycogen synthase kinase-3beta (GSK-3beta) and Axin. Concurrent with the
      inhibition of Wnt/beta-catenin signaling, 1-benzyl-I3C strongly downregulated
      expression of the melanoma master regulator, microphthalmia-associated
      transcription factor isoform-M (MITF-M) by inhibiting promoter activity through
      the consensus lymphoid enhancer factor-1 (LEF-1)/T-cell transcription factor
      (TCF) DNA-binding site. Chromatin immunoprecipitation revealed that 1-benzyl-I3C
      downregulated interactions of endogenous LEF-1 with the MITF-M promoter. 1-Benzyl
      I3C ablated Wnt-activated LEF-1-dependent reporter gene activity in a TOP FLASH
      assay that was rescued by expression of a constitutively active form of the Wnt
      co-receptor low-density lipoprotein receptor-related protein (LRP6), indicating
      that 1-benzyl-I3C disrupts Wnt/beta-catenin signaling at or upstream of LRP6. In
      oncogenic BRAF-expressing melanoma cells, combinations of 1-benzyl-I3C and
      Vemurafenib, a clinically employed BRAF inhibitor, showed strong anti
      proliferative effects. Taken together, our observations demonstrate that 1-benzyl
      I3C represents a new and highly potent indolecarbinol-based small molecule
      inhibitor of Wnt/beta-catenin signaling that has intriguing translational
      potential, alone or in combination with other anti-cancer agents, to treat human
      melanoma.

PMID- 29028957
TI  - Long-term Mortality and Disability in Cryptococcal Meningitis: A Systematic
      Literature Review.
AB  - Cryptococcal meningitis (CM) is the primary cause of meningitis in adults with
      human immunodeficiency virus (HIV) infection and an emerging disease in HIV
      seronegative individuals. No literature review has studied the long-term outcome
      of CM. We performed a systematic review on the long-term (>=3-month) impact of CM
      (Cryptococcus neoformans and Cryptococcus gattii) on mortality and disability in
      HIV-infected and non-HIV-infected adults. Although the quality of current
      evidence is limited, the long-term impact of CM on survival and disability seems
      to be high. One-year mortality ranged from 13% in an Australian non-HIV-infected
      C. gattii-infected cohort to 78% in a Malawian HIV-infected cohort treated with
      fluconazole monotherapy. One-year impairment proportions among survivors ranged
      from 19% in an Australian C. gattii cohort to >70% in a Taiwanese non-HIV- and
      HIV-infected cohorts. Ongoing early therapeutic interventions, early detection of
      impairments and access to rehabilitation services may significantly improve
      patients' survival and quality of life.

PMID- 29028959
TI  - Effectiveness of Measles Vaccination and Immune Globulin Post-Exposure
      Prophylaxis in an Outbreak Setting-New York City, 2013.
AB  - Background: Measles, mumps, and rubella vaccine (MMR) or immune globulin (IG) are
      routinely used for measles post-exposure prophylaxis (PEP). However, current
      literature on the effectiveness of measles PEP is limited and variable. Here, we
      examined the effectiveness of MMR and IG PEP among children exposed to measles
      during an outbreak in New York City (NYC) in 2013. Methods: Contacts were
      identified by the NYC Department of Health and Mental Hygiene between 13 March
      2013 and 30 June 2013. Immunity to measles and receipt of PEP was determined for
      contacts. PEP effectiveness [(1 - relative risk of developing measles) * 100] was
      calculated for MMR, IG, and any PEP (MMR or IG) for nonimmune contacts aged <19
      years. Results: A total of 3409 contacts were identified, of which 208 (6.1%),
      274 (8.0%), and 318 (9.3%) met the inclusion criteria for analysis of MMR, IG,
      and any PEP effectiveness, respectively. Of the contacts included, 44 received
      MMR PEP and 77 received IG PEP. Effectiveness of MMR PEP was 83.4% (95%
      confidence interval [CI], 34.4%, 95.8%). No contact who received IG PEP developed
      measles; effectiveness of IG PEP was 100% (approximated 95% CI, 56.2%, 99.8%).
      Effectiveness of receiving any PEP (MMR or IG) was 92.9% (95% CI, 56.2%, 99.8%).
      Conclusions: Contacts who received PEP were less likely to develop disease. Our
      findings support current recommendations for administration of PEP following
      exposure to measles. These results highlight the importance of a rapid public
      health outbreak response to limit measles transmission following case
      identification.

PMID- 29028958
TI  - Development of Clinical Prediction Models for Surgery and Complications in
      Crohn's Disease.
AB  - Background and Aims: Crohn's disease-related complications account for a
      substantial proportion of inflammatory bowel disease-associated health care
      expenditure. Identifying patients at risk for complications may allow for
      targeted use of early therapeutic interventions to offset this natural course. We
      aimed to develop risk prediction models for Crohn's disease-related surgery and
      complications. Methods: Using data from the Randomised Evaluation of an Algorithm
      for Crohn's Disease cluster-randomised clinical Trial [REACT], which involved
      1898 patients from 40 community practices, separate prediction models were
      derived and internally validated for predicting Crohn's disease-related surgery
      and disease-related complications [defined as the first disease-related surgery,
      hospitalisation, or complication within 24 months]. Model performance was
      assessed in terms of discrimination and calibration, decision curves, and net
      benefit analyses. Results: There were 130 [6.8%] disease-related surgeries and
      504 [26.6%] complications during the 24-month follow-up period. Selected baseline
      predictors of surgery included age, gender, disease location, Harvey-Bradshaw
      Index [HBI] score, stool frequency, antimetabolite or 5-aminosalicylate use, and
      the presence of a fistula, abscess, or abdominal mass. Selected predictors of
      complications included those same factors for surgery, plus corticosteroid or
      anti-tumour necrosis factor use, but excluded 5-aminosalicylate use.
      Discrimination ability, as measured by validated c-statistics, was 0.70 and 0.62
      for the surgery and complication models, respectively. Score charts and nomograms
      were developed to facilitate future risk score calculation. Conclusions: Separate
      risk prediction models for Crohn's disease-related surgery and complications were
      developed using clinical trial data involving community gastroenterology
      practices. These models could be used to guide Crohn's disease management.
      External validation is warranted.

PMID- 29028961
TI  - Towards unified quality verification of synthetic count data with countsimQC.
AB  - Summary: Statistical tools for biological data analysis are often evaluated using
      synthetic data, designed to mimic the features of a specific type of experimental
      data. The generalizability of such evaluations depends on how well the synthetic
      data reproduce the main characteristics of the experimental data, and we argue
      that an assessment of this similarity should accompany any synthetic dataset used
      for method evaluation. We describe countsimQC, which provides a straightforward
      way to generate a stand-alone report that shows the main characteristics of (e.g.
      RNA-seq) count data and can be provided alongside a publication as verification
      of the appropriateness of any utilized synthetic data. Availability and
      implementation: countsimQC is implemented as an R package (for R versions >= 3.4)
      and is available from https://github.com/csoneson/countsimQC under a GPL (>=2)
      license. Contact: charlotte.soneson@uzh.ch or mark.robinson@imls.uzh.ch.

PMID- 29028963
TI  - ZCCHC17 is a master regulator of synaptic gene expression in Alzheimer's disease.
AB  - Motivation: In an effort to better understand the molecular drivers of synaptic
      and neurophysiologic dysfunction in Alzheimer's disease (AD), we analyzed
      neuronal gene expression data from human AD brain tissue to identify master
      regulators of synaptic gene expression. Results: Master regulator analysis
      identifies ZCCHC17 as normally supporting the expression of a network of synaptic
      genes, and predicts that ZCCHC17 dysfunction in AD leads to lower expression of
      these genes. We demonstrate that ZCCHC17 is normally expressed in neurons and is
      reduced early in the course of AD pathology. We show that ZCCHC17 loss in rat
      neurons leads to lower expression of the majority of the predicted synaptic
      targets and that ZCCHC17 drives the expression of a similar gene network in
      humans and rats. These findings support a conserved function for ZCCHC17 between
      species and identify ZCCHC17 loss as an important early driver of lower synaptic
      gene expression in AD. Availability and implementation: Matlab and R scripts used
      in this paper are available at https://github.com/afteich/AD_ZCC. Contact:
      aft25@cumc.columbia.edu. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29028960
TI  - Ovarian Follicular Theca Cell Recruitment, Differentiation, and Impact on
      Fertility: 2017 Update.
AB  - The major goal of this review is to summarize recent exciting findings that have
      been published within the past 10 years that, to our knowledge, have not been
      presented in detail in previous reviews and that may impact altered follicular
      development in polycystic ovarian syndrome (PCOS) and premature ovarian failure
      in women. Specifically, we will cover the following: (1) mouse models that have
      led to discovery of the derivation of two precursor populations of theca cells in
      the embryonic gonad; (2) the key roles of the oocyte-derived factor growth
      differentiation factor 9 on the hedgehog (HH) signaling pathway and theca cell
      functions; and (3) the impact of the HH pathway on both the specification of
      theca endocrine cells and theca fibroblast and smooth muscle cells in developing
      follicles. We will also discuss the following: (1) other signaling pathways that
      impact the differentiation of theca cells, not only luteinizing hormone but also
      insulinlike 3, bone morphogenic proteins, the circadian clock genes, androgens,
      and estrogens; and (2) theca-associated vascular, immune, and fibroblast cells,
      as well as the cytokines and matrix factors that play key roles in follicle
      growth. Lastly, we will integrate what is known about theca cells from mouse
      models, human-derived theca cell lines from patients who have PCOS and patients
      who do not have PCOS, and microarray analyses of human and bovine theca to
      understand what pathways and factors contribute to follicle growth as well as to
      the abnormal function of theca.

PMID- 29028965
TI  - Tuberculin Skin Test Conversions and Occupational Exposure Risk in US Healthcare
      Workers.
AB  - Background: Healthcare workers (HCWs) undergo occupational tuberculosis screening
      at regular intervals. However, the risk of contracting tuberculosis at the
      workplace in a setting with a low background tuberculosis incidence is unclear.
      We aimed to evaluate the risk of tuberculin skin test (TST) conversion and the
      risk of occupational tuberculosis infection among HCWs in such a setting.
      Methods: We conducted a retrospective cohort study of employees of a large
      tertiary medical center in the US Midwest who had undergone TST screening during
      the study period 1 January 1998 to 31 May 2014. Results: Among 40142 HCWs who
      received a TST, only 123 converted over 16.4 years. Only 9 (7%) of the converters
      had a suspected tuberculosis exposure at the workplace and none developed active
      tuberculosis. The majority of TST converters (66%) had a negative QuantiFERON-TB
      test at the time of the conversion. Conclusions: In one of the largest cohorts of
      HCWs in a low-tuberculosis-incidence setting, we demonstrated an extremely low
      risk of occupational tuberculosis exposure among TST converters and no resulting
      active tuberculosis cases. In this setting, the approach of testing HCWs at
      baseline and after tuberculosis exposure, rather than at regular intervals,
      should be considered.

PMID- 29028962
TI  - Clinical Features of Acute Flaccid Myelitis Temporally Associated With an
      Enterovirus D68 Outbreak: Results of a Nationwide Survey of Acute Flaccid
      Paralysis in Japan, August-December 2015.
AB  - Background: Acute flaccid myelitis (AFM) is an acute flaccid paralysis syndrome
      with spinal motor neuron involvement of unknown etiology. We investigated the
      characteristics and prognostic factors of AFM clusters coincident with an
      enterovirus D68 (EV-D68) outbreak in Japan during autumn 2015. Methods: An AFM
      case series study was conducted following a nationwide survey from August to
      December 2015. Radiographic and neurophysiologic data were subjected to
      centralized review, and virology studies were conducted for available specimens.
      Results: Fifty-nine AFM cases (58 definite, 1 probable) were identified,
      including 55 children and 4 adults (median age, 4.4 years). The AFM epidemic
      curve showed strong temporal correlation with EV-D68 detection from pathogen
      surveillance, but not with other pathogens. EV-D68 was detected in 9 patients: 5
      in nasopharyngeal, 2 in stool, 1 in cerebrospinal fluid (adult case), and 1 in
      tracheal aspiration, nasopharyngeal, and serum samples (a pediatric case with
      preceding steroid usage). Cases exhibited heterogeneous paralysis patterns from 1
      to 4-limb involvement, but all definite cases had longitudinal spinal gray
      matter lesions on magnetic resonance imaging (median, 20 spinal segments).
      Cerebrospinal fluid pleocytosis was observed in 50 of 59 cases (85%), and 8 of 29
      (28%) were positive for antiganglioside antibodies, as frequently observed in
      Guillain-Barre syndrome. Fifty-two patients showed variable residual weakness at
      follow-up. Good prognostic factors included a pretreatment manual muscle strength
      test unit score >3, normal F-wave persistence, and EV-D68-negative status.
      Conclusions: EV-D68 may be one of the causative agents for AFM, while host
      susceptibility factors such as immune response could contribute to AFM
      development.

PMID- 29028964
TI  - The Cost-Effectiveness of Human Immunodeficiency Virus Testing and Treatment
      Engagement Initiatives in British Columbia, Canada: 2011-2013.
AB  - Background: Recognition of the secondary preventive benefits of antiretroviral
      therapy (ART) has mobilized global efforts to "seek, test, treat, and retain"
      people living with human immunodeficiency virus [HIV]/AIDS (PLHIV) in HIV care.
      We aimed to determine the cost-effectiveness of a set of HIV testing and
      treatment engagement interventions initiated in British Columbia, Canada, in 2011
      2013. Methods: Using a previously validated dynamic HIV transmission model,
      linked individual-level health administrative data for PLHIV, and aggregate-level
      HIV testing data, we estimated the cost-effectiveness of primary care testing
      (hospital, emergency department [ED], outpatient), ART initiation, and ART
      retention initiatives vs a counterfactual scenario that approximated the status
      quo. HIV incidence, mortality, costs (in 2015$CDN), quality-adjusted life years
      (QALYs), and incremental cost-effectiveness ratios were estimated. Analyses were
      executed over 5- to 25-year time horizons from a government-payer perspective.
      Results: ED testing was the best value at $30216 per QALY gained and had the
      greatest impact on incidence and mortality among PLHIV, while ART initiation
      provided the greatest QALY gains. The ART retention initiative was not cost
      effective. Delivered in combination at the observed scale and sustained
      throughout the study period, we estimated a 12.8% reduction in cumulative HIV
      incidence and a 4.7% reduction in deaths among PLHIV at $55258 per QALY gained.
      Results were most sensitive to uncertainty in the number of undiagnosed PLHIV.
      Conclusions: HIV testing and ART initiation interventions were cost-effective,
      while the ART retention intervention was not. Developing strategies to reengage
      PLHIV lost to care is a priority moving forward.

PMID- 29028967
TI  - Response to 'The end of the dosage of 6 Thioguanine nucleotides? Not so sure...'.

PMID- 29028966
TI  - High Rates of Subsequent Asymptomatic Sexually Transmitted Infections and Risky
      Sexual Behavior in Patients Initially Presenting With Primary Human
      Immunodeficiency Virus-1 Infection.
AB  - Background: Knowledge of the risk factors of individuals with an asymptomatic
      sexually transmitted infection (STI) is essential for implementation of targeted
      STI screening strategies. Methods: Between June 2015 and January 2017, an STI
      screening was offered to all participants in the Zurich Primary human
      immunodeficiency virus (HIV)-1 Infection study. Patients were tested for
      gonorrhea, chlamydia, syphilis, and hepatitis C virus (HCV). Results: Of 214
      participants, 174 (81%) were screened at least once. Most patients were men who
      have sex with men (MSM) (87.4%). Presenting with a primary HIV infection was
      associated with higher odds for later risky sexual behavior, as compared with
      presenting in the chronic phase (odds ratio [OR], 5.58; 95% confidence interval
      [CI], 3.68-8.8). In total, 79 STIs were detected, reflecting a high period
      prevalence of 33.3% (58 of 174 patients). Sixty-six percent of patients (52 of
      79) were asymptomatic. Most common STIs were chlamydia (50.6%; 40 of 79
      patients), gonorrhea (25.3%; 20 of 79), and syphilis (19%; 15 of 79). In a
      multivariable model, engaging in insertive (OR, 6.48; 95% CI, 1.14-36.76) or both
      insertive and receptive (4.61; 1.01-20.96) anal intercourse, STI symptoms (3.4;
      1.68-6.89), and condomless sex (2.06; 1.14-3.74) were positively correlated with
      a positive screening result. The hazard of an incident STI increased with the
      presence of STI symptoms (hazard ratio, 3.03; 95% CI, 1.17-7.84) and any recent
      drug use (2.63; 1-6.9). Conclusions: A trimonthly STI screening including
      asymptomatic individuals should be considered in this population, particularly in
      MSM who report sexual risk behavior. Clinical Trial Registration: NCT 00537966.

PMID- 29028968
TI  - "Cleaved Lymphocytes" Could Be Induced by Pertussis Toxin Injection in Mice, and
      Are Actually Not Lymphocytes.

PMID- 29028969
TI  - Corrigendum: Correlation of defective mitotic checkpoint with aberrantly reduced
      expression of MAD2 protein in nasopharyngeal carcinoma cells.

PMID- 29028971
TI  - Infrequent Testing of Women for Rectal Chlamydia and Gonorrhea in the United
      States.
AB  - Background: Anal sex is a common sexual behavior among women that increases their
      risk of acquiring rectal infection with Chlamydia trachomatis (CT) and Neisseria
      gonorrhoeae (GC). Methods: We estimated the frequency and positivity of rectal CT
      and GC tests for women aged 15-60 years performed by a large US commercial
      laboratory between November 2012 and September 2015. We also estimated the
      frequency and positivity of pharyngeal and genital specimens also performed on
      the same date. Among women with a positive CT or GC result, we estimated the
      frequency and positivity of recommended repeat testing within 12 months. Results:
      Of 5499 women who had rectal CT and GC tests, positivity was 10.8%. On the same
      date, approximately 80% also had genital CT tests, genital GC tests, and
      pharyngeal GC tests, while 40% had pharyngeal CT tests. Rectal CT or GC infection
      was associated with genital CT or GC infection, but 46.5% of rectal CT and GC
      infections would not have been identified with genital testing alone. Among women
      with a rectal CT or GC infection, only 20.0% had a recommended repeat rectal
      test. Of those who had a repeat test, 17.7% were positive. Conclusions: Testing
      women for rectal CT and GC was infrequent, but positive tests were often found in
      women with negative genital tests. Most women with positive rectal tests were not
      retested. Interventions are needed to increase extragenital CT and GC testing of
      at-risk women.

PMID- 29028970
TI  - Poor Obstetric and Infant Outcomes in Human Immunodeficiency Virus-Infected
      Pregnant Women With Tuberculosis in South Africa: The Tshepiso Study.
AB  - Background: Before the wide availability of antiretroviral therapy (ART),
      tuberculosis and human immunodeficiency virus (HIV) disease among pregnant women
      resulted in poor maternal and neonatal outcomes, including high rates of mother
      to-child transmission of both HIV and tuberculosis. We aimed to describe the
      impact of tuberculosis among HIV-infected mothers on obstetric and infant
      outcomes in a population with access to ART. Methods: In this prospective cohort
      study, we followed up HIV-infected pregnant women with or without tuberculosis
      disease from January 2011 through January 2014 in Soweto, South Africa. Two
      controls were enrolled for each case patient, matched by enrollment time,
      maternal age, gestational age, and planned delivery clinic and followed up for 12
      months after delivery. Results: We recruited 80 case patients and 155 controls,
      resulting in 224 live-born infants. Infants of mothers with HIV infection and
      tuberculosis disease had a higher risk of low birth weight (20.8% vs 10.7%; P =
      .04), prolonged hospitalization at birth (51% vs 16%; P < .001), infant death (68
      vs 7 deaths per 1000 births; P < .001), and tuberculosis disease (12% vs 0%; P <
      .001) despite appropriate maternal therapy and infant tuberculosis preventive
      therapy. HIV transmission was higher among these infants (4.1% vs 1.3%; P = .20),
      though this difference was not statistically significant. Obstetric outcomes in
      coinfected women were also poorer with higher risks of maternal hospitalization
      (25% vs 11%; P = .005) and preeclampsia (5.5% vs 0.7%; P = .03). Conclusions:
      Tuberculosis in HIV coinfected pregnant women remains a significant threat to the
      health of both mothers and infants. Improving tuberculosis prevention and early
      diagnosis among pregnant women is critical.

PMID- 29028972
TI  - The Challenge of Vaccine Policy-making With Imperfect Data.

PMID- 29028974
TI  - Temporal Dynamics of Human Frontal and Cingulate Neural Activity During Conflict
      and Cognitive Control.
AB  - Cognitive control refers to the ability to produce flexible, goal-oriented
      behavior in the face of changing task demands and conflicting response
      tendencies. A classic cognitive control experiment is the Stroop-color naming
      task, which requires participants to name the color in which a word is written
      while inhibiting the tendency to read the word. By comparing stimuli with
      conflicting word-color associations to congruent ones, control processes over
      response tendencies can be isolated. We assessed the spatial specificity and
      temporal dynamics in the theta and gamma bands for regions engaged in detecting
      and resolving conflict in a cohort of 13 patients using a combination of high
      resolution surface and depth recordings. We show that cognitive control manifests
      as a sustained increase in gamma band power, which correlates with response time.
      Conflict elicits a sustained gamma power increase but a transient theta power
      increase, specifically localized to the left cingulate sulcus and bilateral
      dorsolateral prefrontal cortex (DLPFC). Additionally, activity in DLPFC is
      affected by trial-by-trial modulation of cognitive control (the Gratton effect).
      Altogether, the sustained local neural activity in dorsolateral and medial
      regions is what determines the timing of the correct response.

PMID- 29028975
TI  - Comparative Responses of Rhagoletis zephyria and Rhagoletis pomonella (Diptera:
      Tephritidae) to Commercial and Experimental Sticky Traps and Odors in Washington
      State.
AB  - Rhagoletis zephyria Snow and Rhagoletis pomonella (Walsh) (Diptera: Tephritidae)
      are morphologically similar flies that attack white-colored snowberry fruit
      (Symphoricarpos spp.) and yellow/red or dark-colored apple/hawthorn fruit
      (Malus/Crataegus spp.), respectively. The two flies are caught together on traps
      in R. pomonella surveys in the western United States, increasing labor needed to
      process catches. Comparing responses of the two species with different traps
      could help identify best practices for reducing R. zephyria captures in these
      surveys and could contribute to understanding population divergence in Rhagoletis
      flies. In Washington State, United States, we found that R. zephyria responded
      most to yellow rectangles and more to white than red spheres (RSs) baited with
      ammonium carbonate (AC), whereas R. pomonella responded most to RSs with AC.
      Yellow plastic rectangles with AC were more effective in capturing R. zephyria
      than cardboard rectangles, as has been found for R. pomonella. R. zephyria did
      not respond to apple fruit volatiles associated with RSs that were attractive to
      R. pomonella. In contrast, R. zephyria responded more to yellow rectangles with
      snowberry than apple volatiles. Both species responded to AC. Our results suggest
      that RSs are better than yellow rectangles for surveying R. pomonella when
      snowberries are abundant. However, if discrimination from R. zephyria is
      paramount, RSs with apple volatiles should be used. Differences in the species'
      responses to traps appear related to odor/color cues of the flies' host fruit,
      while commonalties appear related to visual/olfactory stimuli associated with
      protein feeding, for which AC is a general attractant.

PMID- 29028976
TI  - Atherosclerotic plaque characterization: a need for a paradigm shift for
      prediction of risk.

PMID- 29028973
TI  - Safety and Immunogenicity of Newborn MVA85A Vaccination and Selective, Delayed
      Bacille Calmette-Guerin for Infants of Human Immunodeficiency Virus-Infected
      Mothers: A Phase 2 Randomized, Controlled Trial.
AB  - Background: Vaccination of human immunodeficiency virus (HIV)-infected infants
      with bacille Calmette-Guerin (BCG) is contraindicated. HIV-exposed newborns need
      a new tuberculosis vaccination strategy that protects against tuberculosis early
      in life and avoids the potential risk of BCG disease until after HIV infection
      has been excluded. Methods: This double-blind, randomized, controlled trial
      compared newborn MVA85A prime vaccination (1 * 108 PFU) vs Candin(r) control,
      followed by selective, deferred BCG vaccination at age 8 weeks for HIV-uninfected
      infants and 12 months follow-up for safety and immunogenicity. Results: A total
      of 248 HIV-exposed infants were enrolled. More frequent mild-moderate
      reactogenicity events were seen after newborn MVA85A vaccination. However, no
      significant difference was observed in the rate of severe or serious adverse
      events, HIV acquisition (n = 1 per arm), or incident tuberculosis disease (n = 5
      MVA85A; n = 3 control) compared to the control arm. MVA85A vaccination induced
      modest but significantly higher Ag85A-specific interferon gamma (IFNgamma)+ CD4+
      T cells compared to control at weeks 4 and 8 (P < .0001). BCG did not further
      boost this response in MVA85A vaccinees. The BCG-induced Ag85A-specific IFNgamma+
      CD4+ T-cell response at weeks 16 and 52 was of similar magnitude in the control
      arm compared to the MVA85A arm at all time points. Proliferative capacity,
      functional profiles, and memory phenotype of BCG-specific CD4 responses were
      similar across study arms. Conclusions: MVA85A prime vaccination of HIV-exposed
      newborns was safe and induced an early modest antigen-specific immune response
      that did not interfere with, or enhance, immunogenicity of subsequent BCG
      vaccination. New protein-subunit and viral-vectored tuberculosis vaccine
      candidates should be tested in HIV-exposed newborns. Clinical Trials
      Registration: NCT01650389.

PMID- 29028977
TI  - Evolving Understanding of the Causes of Pneumonia in Adults, With Special
      Attention to the Role of Pneumococcus.
AB  - Before 1945, Streptococcus pneumoniae caused more than 90% of cases of pneumonia
      in adults. After 1950, the proportion of pneumonia caused by pneumococcus began
      to decline. Pneumococcus has continued to decline; at present, this organism is
      identified in fewer than fewer10%-15% of cases. This proportion is higher in
      Europe, a finding likely related to differences in vaccination practices and
      smoking. Gram-negative bacilli, Staphylococcus aureus, Chlamydia, Mycoplasma, and
      Legionella are each identified in 2%-5% of patients with pneumonia who require
      hospitalization. Viruses are found in 25% of patients, up to one-third of these
      have bacterial coinfection. Recent studies fail to identify a causative organism
      in more than 50% of cases, which remains the most important challenge to
      understanding lower respiratory infection. Our findings have important
      implications for antibiotic stewardship and should be considered as new policies
      for empiric pneumonia management are developed.

PMID- 29028978
TI  - Comparative Epidemiology and Outcomes of Human Immunodeficiency virus (HIV), Non
      HIV Non-transplant, and Solid Organ Transplant Associated Cryptococcosis: A
      Population-Based Study.
AB  - In this population-based study in the contemporary era in the United States, the
      proportion of human immunodeficiency virus (HIV)-negative patients with
      cryptococcosis approaches that in HIV-infected patients. Cryptococcosis is
      associated with higher mortality rates in HIV-negative patients (including organ
      transplant recipients).

PMID- 29028979
TI  - 2017 European Society of Cardiology (ESC) focused update on dual antiplatelet
      therapy in collaboration with the European Association for Cardio-Thoracic
      Surgery (EACTS).

PMID- 29028982
TI  - TROVE: A User-friendly Tool for Visualizing and Analyzing Cancer Hallmarks in
      Signaling Networks.
AB  - Summary: Cancer hallmarks, a concept that seeks to explain the complexity of
      cancer initiation and development, provide a new perspective of studying cancer
      signaling which could lead to a greater understanding of this complex disease.
      However, to the best of our knowledge, there is currently a lack of tools that
      support such hallmark-based study of the cancer signaling network, thereby
      impeding the gain of knowledge in this area. We present TROVE, a user-friendly
      software that facilitates hallmark annotation, visualization and analysis in
      cancer signaling networks. In particular, TROVE facilitates hallmark analysis
      specific to particular cancer types. Availability and Implementation: Available
      under the Eclipse Public License from:
      https://sites.google.com/site/cosbyntu/softwares/trove and
      https://github.com/trove2017/Trove. Contact: hechua@ntu.edu.sg or
      assourav@ntu.edu.sg.

PMID- 29028980
TI  - Influenza Among Young Children in Bangladesh: Clinical Characteristics and
      Outcomes From a Randomized Clinical Trial.
AB  - Background: Influenza causes substantial morbidity in children worldwide,
      although influenza vaccine is seldom used in low-resource settings. More
      information on the clinical presentation of influenza and the efficacy of vaccine
      is needed to inform policy. Methods: In 2013 we conducted a randomized, placebo
      controlled clinical trial of live attenuated influenza vaccine (LAIV) in children
      aged 24-59 months in Bangladesh (N = 1761). If participants met prespecified
      specimen collection criteria, we collected nasopharyngeal washes for testing by
      singleplex reverse-transcription polymerase chain reaction (RT-PCR) for
      laboratory-confirmed influenza virus infection (LCI). A panel of RT-PCR assays
      was used to detect noninfluenza respiratory viruses. Primary efficacy results
      have been reported. In this analysis of prespecified and post hoc objectives from
      the trial, we compared signs and symptoms between LCI and non-LCI cases and
      estimated the efficacy of LAIV against moderate-to-severe LCI and other
      prespecified non-LCI clinical outcomes including all-cause pneumonia and acute
      otitis media. Results: The most common signs and symptoms of LCI were fever,
      cough, and runny nose. The combination of subjective fever and cough had a 63%
      sensitivity for LCI. The combination of measured fever, cough, and runny nose was
      most specific (90%) but had low sensitivity (32%) for LCI. The efficacy of LAIV
      against vaccine-strain moderate-to-severe LCI was 56.7% (95% confidence interval,
      9.5%-79.2%). No statistically significant vaccine efficacy was found against the
      non-laboratory-confirmed clinical outcomes. Conclusions: It was not possible to
      distinguish LCI from noninfluenza viral infections on clinical evaluations alone
      in this population of Bangladeshi children. LAIV was efficacious against moderate
      to-severe LCI. Clinical Trials Registration: NCT01797029.

PMID- 29028983
TI  - Guidelines on informed consent in anaesthesia: unrealistic, unethical,
      untenable....

PMID- 29028981
TI  - Tofacitinib in Patients with Ulcerative Colitis: Health-Related Quality of Life
      in Phase 3 Randomised Controlled Induction and Maintenance Studies.
AB  - Background and Aims: Tofacitinib is an oral, small molecule Janus kinase [JAK]
      inhibitor that is being investigated for ulcerative colitis [UC]. We evaluated
      health-related quality of life [HRQoL] in tofacitinib UC Phase 3 studies.
      Methods: Patients >= 18 years old in OCTAVE Induction 1 [N = 598] and 2 [N = 541]
      with moderately to severely active UC were randomised [1:4] to placebo or
      tofacitinib 10 mg twice daily [BID] for 8 weeks. Subsequently, OCTAVE Sustain re
      randomised [1:1:1] clinical responders [N = 593] from induction studies to
      placebo, tofacitinib 5 mg BID, or 10 mg BID, for 52 weeks. Inflammatory Bowel
      Disease Questionnaire [IBDQ] and SF-36v2(r) Health Survey [SF-36v2] assessed
      HRQoL. Results: In OCTAVE Induction 1 and 2, mean changes from baseline IBDQ were
      greater with tofacitinib 10 mg BID at Week 8 [28.9 and 31.5] versus placebo [15.4
      and 17.2; p < 0.0001]; mean changes from baseline SF-36v2 Physical and Mental
      Component Summaries [PCS/MCS] were also greater with 10 mg BID [PCS: 6.8 and 6.8;
      MCS: 6.8 and 7.6] versus placebo [PCS: 2.5 and 4.6; MCS: 3.5 and 4.4; p < 0.01].
      In OCTAVE Sustain atWeek 52, changes in IBDQ were maintained with tofacitinib 5
      mg [-1.3] and 10 mg BID [0.6], and larger with placebo [-20.2; p < 0.0001].
      Changes in SF-36v2 PCS/MCS were also maintained with 5 mg [PCS: 0.0; MCS: -1.0]
      and 10 mg BID [PCS: 0.3; MCS: 0.1] versus placebo [PCS: -5.2; MCS: -6.7; p <
      0.0001] at Week 52 in OCTAVE Sustain. Conclusions: Tofacitinib 10 mg BID
      induction therapy significantly improved HRQoL versus placebo at Week 8.
      Improvements were maintained through 52 weeks' maintenance therapy with
      tofacitinib 5 mg and 10 mg BID. ClinicalTrials.gov registration numbers:
      NCT01465763, NCT01458951 and NCT01458574.

PMID- 29028984
TI  - A Bayesian framework for the inference of gene regulatory networks from time and
      pseudo-time series data.
AB  - Motivation: Molecular profiling techniques have evolved to single-cell assays,
      where dense molecular profiles are screened simultaneously for each cell in a
      population. High-throughput single-cell experiments from a heterogeneous
      population of cells can be experimentally and computationally sorted as a
      sequence of samples pseudo-temporally ordered samples. The analysis of these
      datasets, comprising a large number of samples, has the potential to uncover the
      dynamics of the underlying regulatory programmes. Results: We present a novel
      approach for modelling and inferring gene regulatory networks from high
      throughput time series and pseudo-temporally sorted single-cell data. Our method
      is based on a first-order autoregressive moving-average model and it infers the
      gene regulatory network within a variational Bayesian framework. We validate our
      method with synthetic data and we apply it to single cell qPCR and RNA-Seq data
      for mouse embryonic cells and hematopoietic cells in zebra fish. Availability and
      implementation: The method presented in this article is available at
      https://github.com/mscastillo/GRNVBEM. Contact: mscastillo@ugr.es.

PMID- 29028985
TI  - Impact of coronary lumen reconstruction on the estimation of endothelial shear
      stress: in vivo comparison of three-dimensional quantitative coronary angiography
      and three-dimensional fusion combining optical coherent tomography.
AB  - Aims: It is not clearly elucidated how the fusion technique improves the accuracy
      of endothelial shear stress (ESS) prediction, in comparison with that of three
      dimensional (3D) quantitative coronary angiography (QCA) alone. We aimed to
      evaluate the difference in geometric measurements and haemodynamic estimation
      between 3D QCA and a 3D fusion model combining 3D QCA and optical coherence
      tomography (OCT). Methods and results: Computational fluid dynamics was assessed
      in the coronary models of 20 patients. In the plane-per-plane comparison, the
      difference and agreement were assessed using a generalized linear mixed model and
      concordance correlation coefficient (CCC), respectively. The haemodynamic feature
      around minimum-lumen-diameter (MLD) was characterized using CCC values calculated
      for 1-mm segments. In comparison with the 3D fusion model, 3D QCA showed a
      shorter maximum lumen diameter (2.54 +/- 0.67 mm vs. 2.78 +/- 0.73 mm, P < 0.001)
      and smaller lumen area (4.81 +/- 2.56 mm2 vs. 5.66 +/- 2.97 mm2, P < 0.001),
      resulting in a significantly higher ESS (4.64 Pa vs. 3.78 Pa, p = 0.029). A more
      asymmetric lumen shape of the 3D fusion model was more likely associated with
      under- and over-estimation of the maximum and minimum lumen diameters in the 3D
      QCA model, respectively. The circumferential ESS variations, which were blunted
      by 3D QCA, showed the worst concordance near the MLD site (CCC = 0.370) on
      segment-based comparison. Conclusion: The 3D fusion technique may be a more
      relevant tool for the haemodynamic simulation of coronary arteries through
      providing more accurate lumen characterization than 3D QCA.

PMID- 29028986
TI  - A new haplotype block detection method for dense genome sequencing data based on
      interval graph modeling of clusters of highly correlated SNPs.
AB  - Motivation: Linkage disequilibrium (LD) block construction is required for
      research in population genetics and genetic epidemiology, including specification
      of sets of single nucleotide polymorphisms (SNPs) for analysis of multi-SNP based
      association and identification of haplotype blocks in high density sequencing
      data. Existing methods based on a narrow sense definition do not allow
      intermediate regions of low LD between strongly associated SNP pairs and tend to
      split high density SNP data into small blocks having high between-block
      correlation. Results: We present Big-LD, a block partition method based on
      interval graph modeling of LD bins which are clusters of strong pairwise LD SNPs,
      not necessarily physically consecutive. Big-LD uses an agglomerative approach
      that starts by identifying small communities of SNPs, i.e. the SNPs in each LD
      bin region, and proceeds by merging these communities. We determine the number of
      blocks using a method to find maximum-weight independent set. Big-LD produces
      larger LD blocks compared to existing methods such as MATILDE, Haploview, MIG ++,
      or S-MIG ++ and the LD blocks better agree with recombination hotspot locations
      determined by sperm-typing experiments. The observed average runtime of Big-LD
      for 13 288 240 non-monomorphic SNPs from 1000 Genomes Project autosome data (286
      East Asians) is about 5.83 h, which is a significant improvement over the
      existing methods. Availability and implementation: Source code and documentation
      are available for download at http://github.com/sunnyeesl/BigLD. Contact:
      yyoo@snu.ac.kr. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 29028987
TI  - In silico structural modeling of multiple epigenetic marks on DNA.
AB  - Availability and implementation: The code together with examples and tutorials
      are available from http://www.cs.ox.ac.uk/mosaics. Contact:
      peter.minary@cs.ox.ac.uk. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29028989
TI  - PHAST, PHASTER and PHASTEST: Tools for finding prophage in bacterial genomes.
AB  - PHAST (PHAge Search Tool) and its successor PHASTER (PHAge Search Tool - Enhanced
      Release) have become two of the most widely used web servers for identifying
      putative prophages in bacterial genomes. Here we review the main capabilities of
      these web resources, provide some practical guidance regarding their use and
      discuss possible future improvements. PHAST, which was first described in 2011,
      made its debut just as whole bacterial genome sequencing and was becoming
      inexpensive and relatively routine. PHAST quickly gained popularity among
      bacterial genome researchers because of its web accessibility, its ease of use
      along with its enhanced accuracy and rapid processing times. PHASTER, which
      appeared in 2016, provided a number of much-needed enhancements to the PHAST
      server, including greater processing speed (to cope with very large submission
      volumes), increased database sizes, a more modern user interface, improved
      graphical displays and support for metagenomic submissions. Continuing
      developments in the field, along with increased interest in automated phage and
      prophage finding, have already led to several improvements to the PHASTER server
      and will soon lead to the development of a successor to PHASTER (to be called
      PHASTEST).

PMID- 29028990
TI  - A giant pulmonary artery aneurysm.

PMID- 29028988
TI  - QuASAR-MPRA: accurate allele-specific analysis for massively parallel reporter
      assays.
AB  - Motivation: The majority of the human genome is composed of non-coding regions
      containing regulatory elements such as enhancers, which are crucial for
      controlling gene expression. Many variants associated with complex traits are in
      these regions, and may disrupt gene regulatory sequences. Consequently, it is
      important to not only identify true enhancers but also to test if a variant
      within an enhancer affects gene regulation. Recently, allele-specific analysis in
      high-throughput reporter assays, such as massively parallel reporter assays
      (MPRAs), have been used to functionally validate non-coding variants. However, we
      are still missing high-quality and robust data analysis tools for these datasets.
      Results: We have further developed our method for allele-specific analysis QuASAR
      (quantitative allele-specific analysis of reads) to analyze allele-specific
      signals in barcoded read counts data from MPRA. Using this approach, we can take
      into account the uncertainty on the original plasmid proportions, over
      dispersion, and sequencing errors. The provided allelic skew estimate and its
      standard error also simplifies meta-analysis of replicate experiments.
      Additionally, we show that a beta-binomial distribution better models the
      variability present in the allelic imbalance of these synthetic reporters and
      results in a test that is statistically well calibrated under the null. Applying
      this approach to the MPRA data, we found 602 SNPs with significant (false
      discovery rate 10%) allele-specific regulatory function in LCLs. We also show
      that we can combine MPRA with QuASAR estimates to validate existing experimental
      and computational annotations of regulatory variants. Our study shows that with
      appropriate data analysis tools, we can improve the power to detect allelic
      effects in high-throughput reporter assays. Availability and implementation:
      http://github.com/piquelab/QuASAR/tree/master/mpra. Contact: fluca@wayne.edu or
      rpique@wayne.edu. Supplementary information: Supplementary data are available
      online at Bioinformatics.

PMID- 29028991
TI  - A Bayesian procedure for estimating the causal effects of nursing home bed-hold
      policy.
AB  - Nursing home bed-hold policies provide continuity of care for Medicaid
      beneficiaries by paying nursing homes to reserve beds so residents can return to
      their facility of occupancy following an acute hospitalization. In 2001, Michigan
      implemented bed-hold policies in nursing homes. We investigated the impact of
      these policies on mortality and hospitalizations using 1999-2004 quarterly data
      from nursing homes in Michigan and nursing homes in 11 states that did not
      implement such policies. Synthetic Control has been used to estimate the effects
      of policies by accounting for changes over time unrelated to the intervention.
      Synthetic Control is intended for scalar continuous outcome at each period, and
      assumes a single treated unit and multiple control units. We propose a Bayesian
      procedure to overcome these limitations. It imputes the outcomes of nursing homes
      in Michigan if they were not exposed to the policy by matching to non-exposed
      nursing homes that are associated with the exposed ones in the pre-policy period.
      Because sampling from a Bayesian model is computationally challenging, we
      describe an approximation procedure that can be implemented using existing
      software. Our approach can be applied to other studies that examine the impact of
      policies.

PMID- 29028992
TI  - Spatial Distribution of Megacopta cribraria (Hemiptera: Plataspidae) Adults, Eggs
      and Parasitism by Paratelenomus saccharalis (Hymenoptera: Platygastridae) in
      Soybean.
AB  - Since 2014, populations of the kudzu bug, Megacopta cribraria (F.) (Hemiptera:
      Plataspidae), have declined in the southeastern United States and seldom require
      treatment. This decline follows the discovery of Paratelenomus saccharalis (Dodd;
      Hymenoptera: Platygastridae), a non-native egg parasitoid. The objective of this
      project was to observe the temporal and spatial dynamics of P. saccharalis
      parasitism of kudzu bug egg masses in commercial soybean fields. Four fields were
      sampled weekly for kudzu bugs and egg masses at a density of one sample per 0.6
      ha. Sampling commenced when soybean reached the R2 maturity stage and continued
      until no more egg masses were present. Responses including kudzu bugs, egg
      masses, and parasitism rates were analyzed using ANOVA, Spatial Analysis by
      Distance Indices (SADIE), and SaTScan spatial analysis software. Egg masses were
      collected from the field, held in the lab and monitored for emergence of kudzu
      bug nymphs or P. saccharalis. Kudzu bug populations were generally lower than
      previously reported in the literature and spatial aggregation was not
      consistently observed. Egg parasitism was first detected in early July and
      increased to nearly 40% in mid-August. Significant spatial patterns in parasitism
      were observed with spatio-temporal clusters being loosely associated with
      clusters of egg masses. There were no significant differences in parasitism rates
      between field margins and interiors, suggesting that P. saccharalis is an
      effective parasitoid of kudzu bug egg masses on a whole-field scale.

PMID- 29028993
TI  - High Prevalence of Multidrug-Resistant Mycoplasma genitalium in Human
      Immunodeficiency Virus-Infected Men Who Have Sex With Men in Alabama.
AB  - We tested for Mycoplasma genitalium in 157 HIV-infected men. Urogenital and
      rectal prevalence were 10.8% and 6.4%. Macrolide resistance mutations were
      detected in 70.6% and 80% of urogenital and rectal samples, and fluoroquinolone
      resistance mutations in 26.7% and 40%, respectively.

PMID- 29028994
TI  - An atypical cause of ST elevation.

PMID- 29028995
TI  - Sinus of Valsalva aneurysm protruding intramurally into right ventricle: does
      size really matter?

PMID- 29028996
TI  - Cold Tolerance of Megacopta cribraria (Hemiptera: Plataspidae): An Invasive Pest
      of Soybeans.
AB  - Kudzu bug, Megacopta cribraria Fabricius (Hemiptera: Plataspidae), first
      discovered in the United States in 2009, is an invasive pest of soybeans. From
      2013 to 2016, Maryland has been the northern limit of its distribution in the
      United States. We sought to determine the physiological cold temperature limits,
      timing of movement to overwintering locations, and to characterize overwintering
      microhabitat temperature. We measured supercooling point (SCP) on three
      populations from distinct USDA plant hardiness zones in Maryland and Virginia
      between October and December of 2015. The average SCP across all sample months
      and populations was -12.6 degrees C and no consistent trend of month or
      population location were observed. Additionally, we assessed the lower lethal
      temperature to kill 50% of the population (LLT50) at the same population
      locations in October and November 2015. The average LLT50 over both months and
      all three population locations was -5.1 degrees C. Again, no consistent trend
      based on population location was observed but we did find a modest depression in
      the LLT50 values between October and November. We observed that kudzu bug
      overwinters in leaf litter and begins to move into the litter in late November to
      early December. Leaf litter moderates day to night temperature differences and
      was warmer than ambient temperature by an average of 0.7 degrees C. Evidence
      suggests that the cold tolerance of the kudzu bug limits its distribution north
      of Maryland.

PMID- 29028997
TI  - Serum Quantitative Proteomic Analysis Reveals Soluble EGFR To Be a Marker of
      Insulin Resistance in Male Mice and Humans.
AB  - To identify circulating factors as candidates involved in type 2 diabetes
      mellitus (T2DM), we conducted two different quantitative proteomic analyses: (1)
      db/db mouse sera were compared with db/+ mouse sera obtained at 4, 8, 12, and 24
      weeks of age, and (2) db/db mouse sera from animals treated with liraglutide were
      compared with sera from animals without liraglutide treatment. Twenty proteins
      were differentially expressed in db/db mouse sera in the first experiment and
      eight proteins were differentially expressed in db/db mouse sera after
      liraglutide treatment in the second experiment. Soluble epidermal growth factor
      receptor (sEGFR) was identified as a common factor, and its protein level was
      significantly affected in both experiments. An enzyme-linked immunosorbent assay
      confirmed that the relatively low serum sEGFR levels in db/db mice were restored
      by liraglutide treatment. The serum sEGFR levels were elevated in diabetic mice
      with impaired insulin secretion and decreased in high-fat diet-fed mice and ob/ob
      mice. The serum sEGFR levels increased after the administration of a dual
      inhibitor of IGF-1/insulin receptor or streptozotocin. In humans with normal
      glucose tolerance or T2DM, the serum sEGFR levels were correlated with the
      fasting blood glucose, fasting serum insulin, homeostatic model assessment of
      insulin resistance, HbA1c, total cholesterol, low-density lipoprotein
      cholesterol, and triglycerides levels. These findings suggest that sEGFR might be
      a biomarker for evaluating insulin resistance or a therapeutic target of
      liraglutide.

PMID- 29028998
TI  - High Cryptococcal Antigen Titers in Blood Are Predictive of Subclinical
      Cryptococcal Meningitis Among Human Immunodeficiency Virus-Infected Patients.
AB  - Background: High mortality rates among asymptomatic cryptococcal antigen (CrAg)
      positive patients identified through CrAg screening, despite preemptive
      fluconazole treatment, may be due to undiagnosed cryptococcal meningitis.
      Methods: Symptoms were reviewed in CrAg-positive patients identified by screening
      19233 individuals with human immunodeficiency virus infection and CD4 cell counts
      <100/uL at 17 clinics and 3 hospitals in Johannesburg from September 2012 until
      September 2015, and at 2 hospitals until June 2016. Cerebrospinal fluid samples
      from 90 of 254 asymptomatic patients (35%) and 78 of 173 (45%) with headache only
      were analyzed for cryptococcal meningitis, considered present if Cryptococcus was
      identified by means of India ink microscopy, culture, or CrAg test. CrAg titers
      were determined with stored blood samples from 62 of these patients. The
      associations between blood CrAg titer, concurrent cryptococcal meningitis, and
      mortality rate were assessed. Results: Cryptococcal meningitis was confirmed in
      34% (95% confidence interval, 25%-43%; 31 of 90) of asymptomatic CrAg-positive
      patients and 90% (81%-96%; 70 of 78) with headache only. Blood CrAg titer was
      significantly associated with concurrent cryptococcal meningitis in asymptomatic
      patients (P < .001) and patients with headache only (P = .003). The optimal titer
      for predicting cryptococcal meningitis was >160 (sensitivity, 88.2%; specificity,
      82.1%); the odds ratio for concurrent cryptococcal meningitis was 34.5 (95%
      confidence interval, 8.3-143.1; P < .001). Conclusions: About a third of
      asymptomatic CrAg-positive patients have concurrent cryptococcal meningitis. More
      effective clinical assessment strategies and antifungal regimens are required for
      CrAg-positive patients, including investigation for cryptococcal meningitis
      irrespective of symptoms. Where it is not possible to perform lumbar punctures in
      all CrAg-positive patients, blood CrAg titers should be used to target those most
      at risk of cryptococcal meningitis.

PMID- 29028999
TI  - Control of Pecan Weevil With Microbial Biopesticides.
AB  - The pecan weevil, Curculio caryae (Horn) (Coleoptera: Curculionidae), is a key
      pest of pecans Carya illinoinensis ([Wangenh.] K. Koch) (Fagales: Juglandaceae).
      Control recommendations rely on broad spectrum chemical insecticides. Due to
      regulatory and environmental concerns, effective alternatives for C. caryae
      control must be sought for pecan production in conventional and organic systems.
      We explored the use of microbial biopesticides for control of C. caryae in
      Georgia pecan orchards. Three experiments were conducted. The first investigated
      an integrated microbial control approach in an organic system at two locations.
      Three microbial agents, Grandevo (based on byproducts of the bacterium
      Chromobacterium subtsugae Martin, Gundersen-Rindal, Blackburn & Buyer), the
      entomopathogenic nematode Steinernema carpocapsae (Weiser), and entomopathogenic
      fungus Beauveria bassiana (Balsamo) Vuillemin, were applied to each treatment
      plot (0.6 ha) at different times during the season. A second experiment compared
      the effects of S. carpocapsae and B. bassiana applied as single treatments
      relative to application of both agents (at different times); survival of C.
      caryae was assessed approximately 11 mo after larvae were added to pots sunk in
      an organic pecan orchard. In a conventional orchard (with 1.0 ha plots), the
      third experiment compared Grandevo applications to a commonly used regime of
      chemical insecticides (carbaryl alternated with a pyrethroid). All experiments
      were repeated in consecutive years. The combined pest management tactic
      (experiment 1) reduced C. caryae infestation relative to non-treated control
      plots in both locations in 2014 and one of the two locations in 2015 (the other
      location had less than 1% infestation). In experiment 2, no differences among
      combined microbial treatments, single-applied microbial treatments or different
      numbers of application were observed, yet all microbial treatments reduced C.
      caryae survival relative to the control. In the third experiment, both Grandevo
      and standard chemical insecticide applications resulted in lower weevil
      infestation than the control (both years) and there was no difference between the
      insecticide treatments in 2014 although the chemical insecticide regime had
      slightly lower infestation in 2015. These results provide evidence that microbial
      biopesticides can substantially reduce pecan weevil infestations in organic and
      nonorganic systems.

PMID- 29029000
TI  - Spindle cell sarcoma of the mitral valve: a rare indication for mitral valve
      replacement.
AB  - Primary cardiac tumours are a rare finding and even rarer cause of valvular heart
      disease. We report a case of cardiac spindle cell sarcoma mimicking mitral valve
      stenosis and the subsequent operative management.

PMID- 29029001
TI  - Comparative study of bicuspid vs. tricuspid aortic valve stenosis.
AB  - Aims: To examine differences and similarities in bicuspid aortic valve (BAV) and
      tricuspid aortic valve (TAV) stenosis occurring during the same age and whether
      any differences impact outcomes following aortic valve replacement (AVR). Methods
      and results: An age-matched cohort of 198 BAV stenosis and 198 TAV stenosis
      patients was identified from 888 consecutive patients undergoing AVR for severe
      AS. Mean age 68 +/- 6 years; 68% male. Patients with BAV were less likely to have
      multiple comorbidities, as measured by the Charlson Comorbidity Index (CCI) >2 (3
      vs. 10%, P = 0.007). Indexed aortic valve area (0.44 +/- 0.09 vs. 0.42 +/- 0.08
      cm2/m2, P = 0.17) and left ventricular ejection fraction (LVEF) were similar (62
      +/- 11 vs. 61 +/- 12%, P = 0.12), but E/e' >=15 (46 vs. 66%, P = 0.0002) was less
      common in BAV stenosis. A tissue aortic valve prosthesis was more commonly
      utilized in both groups (81 vs. 78%, P = 0.54). Overall indexed effective orifice
      area was larger in BAV compared with TAV (1.08 +/- 0.33 vs. 0.96 +/- 0.25 cm2/m2,
      P = 0.0008). Five-year survival following AVR was lower in TAV compared with BAV
      stenosis (61 vs. 79%, P = 0.02). Independent predictors of survival following AVR
      were LVEF < 50% [hazard ratio (HR): 4.8, P = 0.0005], CCI > 2 (HR: 3.1, P =
      0.015), effective orifice area index <=0.85 cm2/m2 (HR: 2.5, P = 0.004), and
      bioprosthesis (HR: 3.7, P = 0.02). Conclusion: In an age-matched cohort, TAV
      compared with BAV stenosis is associated with greater prevalence of
      cardiovascular risk factors and cardiac impairment and worse survival after AVR.

PMID- 29029002
TI  - Infrared intraoperative fluorescence imaging using indocyanine green in thoracic
      surgery.
AB  - Thoracic surgery faces many unique challenges that require innovative solutions.
      The increase in utilization of minimally invasive practices, poor overall cancer
      survival and significant morbidity of key operations remain key obstacles to
      overcome. Intraoperative fluorescence imaging is a process by which fluorescent
      dyes and imaging systems are used as adjuncts for surgeons in the operating room.
      Other surgical subspecialists have shown that intraoperative fluorescence imaging
      can be applied as a practical adjunct to their practices. Thoracic surgeons over
      the last 15 years have also used intraoperative fluorescence imaging for sentinel
      lymph node mapping, lung mapping, oesophageal conduit vascular perfusion and lung
      nodule identification. This review describes some of the key studies that
      demonstrate the applications of intraoperative near-infrared fluorescence
      imaging.

PMID- 29029003
TI  - Rearing Xyleborus volvulus (Coleoptera: Curculionidae) on Media Containing
      Sawdust from Avocado or Silkbay, With or Without Raffaelea lauricola
      (Ophiostomatales: Ophiostomataceae).
AB  - Like other ambrosia beetles, Xyleborus volvulus Fabricius (Coleoptera:
      Curculionidae) lives in a mutualistic symbiotic relationship with fungi that
      serve as food source. Until recently, X. volvulus was not considered a pest, and
      none of its symbionts were considered plant pathogens. However, recent reports of
      an association between X. volvulus and Raffaelea lauricola T.C. Harr., Fraedrich
      & Aghayeva (Ophiostomatales: Ophiostomataceae), the cause of the laurel wilt
      disease of avocado (Persea americana Mill. [Laurales: Lauraceae]), and its
      potential role as vector of the pathogen merit further investigation. The
      objective of this study was to evaluate three artificial media containing sawdust
      obtained from avocado or silkbay (Persea humilis Nash) for laboratory rearing of
      X. volvulus. The effect of R. lauricola in the media on the beetle's reproduction
      was also evaluated. Of the three media, the one with the lowest content of
      sawdust and intermediate water content provided the best conditions for rearing
      X. volvulus. Reproduction on this medium was not affected by the sawdust species
      or the presence of R. lauricola. On the other two media, there was a significant
      interaction between sawdust species and R. lauricola. The presence of R.
      lauricola generally had a negative effect on brood production. There was limited
      colonization of the mycangia of X. volvulus by R. lauricola on media inoculated
      with the pathogen. From galleries formed within the best medium, there was 50%
      recovery of R. lauricola, but recovery was much less from the other two media.
      Here, we report the best artificial substrate currently known for X. volvulus.

PMID- 29029004
TI  - Right ventricular thickening and extensive late gadolinium enhancement in a
      patient with rare case of isolated cardiac sarcoidosis and initially negative
      biopsy.

PMID- 29029006
TI  - Large-scale assessment of aortic stenosis: facing the next cardiac epidemic?
AB  - Aims: Aortic stenosis (AS) is the most frequent valvular disease in developed
      countries. As society grows older, the prevalence of AS increases. However, the
      real burden, current aetiology, severity distribution, and echocardiographic
      patterns of AS are not fully clear. The aim of the present study is to provide an
      accurate overall picture of AS, focusing on its epidemiology, aetiology, and
      echocardiographic features. Methods and results: A total of 29 502 consecutive
      echocardiograpies were prospectively included in this multicentre study. The
      present sample was composed of patients with advanced age (mean 75.2 years) and
      similar gender distribution. High proportion (7.2%) showed any grade of AS, with
      important number of patients (2.8%) presenting severe AS, most of them aged 75
      years or more. Coexisting valvular disease appeared in almost half of the sample
      (49.6%), being the most frequently diagnosed aortic regurgitation (AR) (22%)
      followed by mitral regurgitation (MR) (15.6%). Degenerative aetiology was found
      in the vast majority (93.4%) of the studies whereas rheumatic is currently
      infrequent (3.35%). Low flow-low gradient (LFLG) appeared in 24.6% of patients
      with severe AS. Atrial fibrillation (23.1% vs. 11.6%; P = 0.002), MR (23.3% vs.
      15.1%; P = 0.018), and right ventricle dysfunction (13.3% vs. 5.2%; P = 0.003)
      appeared frequently in LFLG group. Conclusions: Burden of AS is higher than
      previously assumed. Degenerative aetiology is the main cause of AS. Most of the
      patients are elder with high prevalence of significant co-existing valvular
      disease. LFLG severe AS is present in an important proportion of patients,
      showing high grade of left ventricle remodelling.

PMID- 29029005
TI  - Biopsy-derived Intestinal Epithelial Cell Cultures for Pathway-based
      Stratification of Patients With Inflammatory Bowel Disease.
AB  - Background: Endoplasmic reticulum [ER] stress was shown to be pivotal in the
      pathogenesis of inflammatory bowel disease. Despite progress in inflammatory
      bowel disease [IBD] drug development, not more than one-third of patients achieve
      steroid-free remission and mucosal healing with current therapies. Furthermore,
      patient stratification tools for therapy selection are lacking. We aimed to
      identify and quantify epithelial ER stress in a patient-specific manner in an
      attempt towards personalised therapy. Methods: A biopsy-derived intestinal
      epithelial cell culture system was developed and characterised. ER stress was
      induced by thapsigargin and quantified with a BiP enzyme-linked immunosorbent
      assay [ELISA] of cell lysates from 35 patients with known genotypes, who were
      grouped based on the number of IBD-associated ER stress and autophagy risk
      alleles. Results: The epithelial character of the cells was confirmed by E
      cadherin, ZO-1, and MUC2 staining and CK-18, CK-20, and LGR5 gene expression.
      Patients with three risk alleles had higher median epithelial BiP-induction [vs
      untreated] levels compared with patients with one or two risk alleles [p = 0.026
      and 0.043, respectively]. When autophagy risk alleles were included and patients
      were stratified in genetic risk quartiles, patients in Q2, Q3, and Q4 had
      significantly higher ER stress [BiP] when compared with Q1 [p = 0.034, 0.040, and
      0.034, respectively]. Conclusions: We developed and validated an ex vivo
      intestinal epithelial cell culture system and showed that patients with more ER
      stress and autophagy risk alleles have augmented epithelial ER stress responses.
      We thus presented a personalised approach whereby patient-specific defects can be
      identified, which in turn could help in selecting tailored therapies.

PMID- 29029007
TI  - Presence of micro- and macroalbuminuria and the association with cardiac
      mechanics in patients with type 2 diabetes.
AB  - Aims: Albuminuria-a marker of generalized vascular dysfunction-is a strong
      predictor of heart failure in patients with type 2 diabetes which may be caused
      by concomitant myocardial dysfunction reflecting the same underlying
      pathogenesis. Methods and results: We included 915 patients with type 2 diabetes
      from two secondary care centres and stratified according to albuminuria status in
      normo-, micro-, and macroalbuminuria. We performed comprehensive echocardiography
      including conventional imaging, tissue Doppler imaging, and 2D speckle tracking.
      Cardiac remodelling occurred in patients with increasing left ventricular (LV)
      mass index and LV wall thicknesses with increasing severity of albuminuria.
      Diastolic measures worsened across groups of albuminuria severity (normo-, micro
      , and macroalbuminuria, respectively): septal e' velocity [mean: 6.9 cm/s (SD
      1.9), 6.4 (1.7), and 5.9 (1.7), P < 0.001], septal E/e' (median: 10.6
      [interquartile range: 8.9-13.2], 12.1 [10.3-14.8], and 12.7 [10.4-16.6], P <
      0.001), and left atrial volume index (24.3 mL/m2 [19.1-29.9], 25.7 [20.0-31.6],
      and 29.0 [22.2-34.9], P < 0.001) In contrast, systolic measures were only
      impaired in patients with macroalbuminuria: global longitudinal strain (GLS): [
      14.6% (2.7) in normo- and -13.3 (2.9) in macroalbuminuria, P < 0.001] and GLS
      rate [mean: -0.79 s-1 (0.17) in normo- and -0.72 (0.16) in macroalbuminuria, P =
      0.001]. The findings persisted in subgroup analyses of patients without known
      coronary heart disease and with normal ejection fraction and in multivariable
      adjusted analyses. Conclusion: In patients with type 2 diabetes, microalbuminuria
      is associated with decreased diastolic function whereas decreased systolic
      function was only associated with macroalbuminuria supporting the notion of
      similar pathogenic mechanisms of albuminuria and impaired myocardial function.

PMID- 29029008
TI  - Complete arterial revascularization using bilateral internal mammary artery in T
      graft technique for multivessel coronary artery disease in on- or off-pump
      approach: does gender lose its historical impact on clinical outcome?
AB  - OBJECTIVES: Higher rates of mortality and morbidity have been reported in women
      undergoing coronary artery bypass grafting (CABG) compared with men. Different
      revascularization techniques (on-pump and off-pump) might influence this outcome.
      METHODS: We retrospectively analysed 3445 consecutively recruited patients (all
      comers) undergoing complete arterial CABG (CACABG) at a single centre between
      January 2000 and December 2012. CACABG was performed in all patients using
      bilateral skeletonized internal mammary artery in T-graft technique, either on
      pump (n = 2216) or off-pump (n = 1229). Early results (30-day) and long-term
      follow-up data were analysed with respect to gender-specific outcome. RESULTS:
      Women were older than men in both groups (P < 0.001), and men had a higher body
      mass index (on-pump: P < 0.001; off-pump: P = 0.02) compared with women. Men
      displayed a higher extent of coronary artery disease (P < 0.001) and an overall
      lower ejection fraction (P < 0.001) when undergoing on-pump CABG. No gender
      differences were observed for late survival (P = 0.74 vs P = 0.52) in on-pump and
      off-pump procedures, respectively. Late follow-up revealed a higher rate of
      FitzGibbon A graft patency in men undergoing the on-pump approach (P = 0.006).
      CONCLUSIONS: CACABG using bilateral internal mammary artery in T-graft technique
      showed excellent early and long-term results. No significant gender-specific
      differences were observed in both groups undergoing CACABG with respect to 30
      days mortality and morbidity as well as late survival. However, late follow-up
      revealed a higher graft patency in men undergoing the on-pump approach, compared
      to women.

PMID- 29029009
TI  - The Effect of Physical Activity and Cardiorespiratory Fitness on All-Cause
      Mortality in Hong Kong Chinese Older Adults.
AB  - Background: It is unclear whether physical activity (PA) could predict all-cause
      mortality independently of cardiorespiratory fitness, and there are relatively
      few studies evaluating the combined effect of PA and cardiorespiratory fitness on
      mortality. Methods: We invited 1,242 Chinese older adults aged 69-94 years from
      the MrOs and MsOs cohort (Hong Kong) study for a 7-year follow-up. PA was
      measured by the Physical Activity Scale of the Elderly (PASE). Cardiorespiratory
      fitness, expressed as maximal oxygen uptake (VO2max), was assessed by performing
      symptom-limited maximal exercise testing on an electrically braked bicycle
      ergometer and 6-m walk test. We aimed to examine the independent and combined
      effect of PA and VO2max with all-cause mortality by cox proportional hazards
      models. Results: Ninety-nine deaths occurred over a mean follow-up of 5.3 +/- 0.8
      years. PA was inversely associated with all-cause mortality in unadjusted and
      fully-adjusted models, and the association was still significant after further
      adjusted for VO2max. In stratified analysis, PA was significantly related to all
      cause mortality within both unfit and fit strata. As compared with those being
      active and fit, physically inactive and cardiorespiratory unfit individuals had
      the highest all-cause mortality risk. Physically active but unfit individuals and
      inactive but fit individuals had similar all-cause mortality risk. Conclusions:
      Among older adults, PA was an important predictor of all-cause mortality
      independently of VO2max. High cardiorespiratory fitness does not necessarily
      confer low mortality risk in physically inactive older adults.

PMID- 29029011
TI  - Obesity and prognosis: Time to forget about metabolically healthy obesity.

PMID- 29029010
TI  - Call for Action: Invasive Fungal Infections Associated With Ibrutinib and Other
      Small Molecule Kinase Inhibitors Targeting Immune Signaling Pathways.
AB  - Opportunistic infections caused by Pneumocystis jirovecii, Cryptococcus
      neoformans, and ubiquitous airborne filamentous fungi have been recently reported
      in patients with hematological cancers historically considered at low risk for
      invasive fungal infections (IFIs), after receipt of the Bruton tyrosine kinase
      inhibitor ibrutinib. The spectrum and severity of IFIs often observed in these
      patients implies the presence of a complex immunodeficiency that may not be
      solely attributed to mere inhibition of Bruton tyrosine kinase. In view of the
      surge in development of small molecule kinase inhibitors for treatment of
      malignant and autoimmune diseases, it is possible that there would be an
      emergence of IFIs associated with the effects of these molecules on the immune
      system. Preclinical assessment of the immunosuppressive effects of kinase
      inhibitors and human studies aimed at improving patient risk stratification for
      development of IFIs could lead to prevention, earlier diagnosis, and better
      outcomes in affected patients.

PMID- 29029012
TI  - Heterogeneity of studies in anesthesiology systematic reviews: a meta
      epidemiological review and proposal for evidence mapping.
AB  - Heterogeneity among the primary studies included in a systematic review (SR) is
      one of the most challenging considerations for systematic reviewers. Current
      practices in anaesthesiology SRs have not been evaluated, but traditional methods
      may not provide sufficient information to evaluate the true nature of these
      differences. We address these issues by examining the practices for evaluating
      heterogeneity in anesthesiology reviews. Also, we propose a mapping method for
      presenting heterogeneous aspects of the primary studies in SRs.We evaluated
      heterogeneity practices reported in SRs published in highly ranked anesthesiology
      journals and Cochrane reviews. Elements extracted from the SRs included
      heterogeneity tests, models used, analyses conducted, plots used, and I2 values.
      Additionally, we selected a SR to develop an evidence map in order to display
      clinical heterogeneity.Our statistical analysis showed 150/207 SRs reporting a
      test for statistical heterogeneity. Plots were used in 138 reviews to display
      heterogeneity. Subgroup analyses were the most commonly reported analysis (54%).
      Meta-regression and sensitivity analyses were used sparingly (25%; 23%
      respectively). A random effects model was most commonly reported (33%).
      Heterogeneity statistics across meta-analyses suggested that, in our sample, the
      majority (55%) did not present sufficient heterogeneity to be of great concern.
      Cochrane reviews (n=58) were also analysed. Plots were used in 88% of Cochrane
      reviews. Subgroup analysis was used in 59% Cochrane reviews, while sensitivity
      analysis was used in 62%.Many reviews did not provide sufficient detail regarding
      heterogeneity. We are calling for improvement to reporting practices.

PMID- 29029013
TI  - An empirical Bayes approach for multiple tissue eQTL analysis.
AB  - Expression quantitative trait locus (eQTL) analyses identify genetic markers
      associated with the expression of a gene. Most up-to-date eQTL studies consider
      the connection between genetic variation and expression in a single tissue. Multi
      tissue analyses have the potential to improve findings in a single tissue, and
      elucidate the genotypic basis of differences between tissues. In this article, we
      develop a hierarchical Bayesian model (MT-eQTL) for multi-tissue eQTL analysis.
      MT-eQTL explicitly captures patterns of variation in the presence or absence of
      eQTL, as well as the heterogeneity of effect sizes across tissues. We devise an
      efficient Expectation-Maximization (EM) algorithm for model fitting. Inferences
      concerning eQTL detection and the configuration of eQTL across tissues are
      derived from the adaptive thresholding of local false discovery rates, and
      maximum a posteriori estimation, respectively. We also provide theoretical
      justification of the adaptive procedure. We investigate the MT-eQTL model through
      an extensive analysis of a 9-tissue data set from the GTEx initiative.

PMID- 29029015
TI  - An experimental study comparing the respiratory effects of tapentadol and
      oxycodone in healthy volunteers.
AB  - Background: There is a clinical need for potent opioids that produce little or no
      respiratory depression. In the current study we compared the respiratory effects
      of tapentadol, a mu-opioid receptor agonist and noradrenaline reuptake inhibitor,
      and oxycodone, a selective mu-opioid receptor agonist. We hypothesize that
      tapentadol 100 mg has a lesser effect on the control of breathing than oxycodone
      20 mg. Methods: Fifteen healthy volunteers were randomized to receive oral
      tapentadol (100 and 150 mg), oxycodone 20 mg or placebo immediate release tablets
      in a crossover double-blind randomized design. The main end-point of the study
      was the effect of treatment on the ventilatory response to hypercapnia and
      ventilation at an extrapolated end-tidal PCO2 of 7.3 kPa (55 mmHg, VE55); VE55
      was assessed prior and for 6-h following drug intake. Results: All three
      treatments had typical opioid effects on the hypercapnic ventilatory response: a
      shift to the right coupled to a decrease of the response slope. Oxycodone 20 mg
      had a significantly larger respiratory depressant effect than tapentadol 100 mg
      (mean difference -5.0 L min-1, 95% confidence interval: -7.1 to -2.9 L min-1,
      P<0.01), but not larger than tapentadol 150 mg (oxycodone vs. tapentadol 150 mg:
      P>0.05). Conclusions: In this exploratory study we observed that both tapentadol
      and oxycodone produce respiratory depression. Tapentadol 100 mg but not 150 mg
      had a modest respiratory advantage over oxycodone 20 mg. Further studies are
      needed to explore how these results translate to the clinical setting.

PMID- 29029014
TI  - 1,25-Dihydroxyvitamin D Regulation of Glutamine Synthetase and Glutamine
      Metabolism in Human Mammary Epithelial Cells.
AB  - Genomic profiling has identified a subset of metabolic genes that are altered by
      1,25-dihydroxyvitamin D (1,25D) in breast cells, including GLUL, the gene that
      encodes glutamine synthetase (GS). In this study, we explored the relevance of
      vitamin D modulation of GLUL and other metabolic genes in the context of
      glutamine utilization and dependence. We show that exposure of breast epithelial
      cells to glutamine deprivation or a GS inhibitor reduced growth and these effects
      were exacerbated by cotreatment with 1,25D. 1,25D downregulation of GLUL was
      sufficient to reduce abundance and activity of GS. Flow cytometry demonstrated
      that glutamine deprivation induced S phase arrest, likely due to reduced
      availability of glutamine for DNA synthesis. In contrast, 1,25D induced G0/G1
      arrest, indicating that its effects are not solely due to reduced glutamine
      synthesis. Indeed, 1,25D also reduced expression of GLS1 and GLS2 genes, which
      code for glutaminases that shunt glutamine into the tricarboxylic acid (TCA)
      cycle. Consistent with reduced entry of glutamine into the TCA cycle, 1,25D
      inhibited glutamine oxidation and the metabolic response to exogenous glutamine
      as analyzed by Seahorse Bioscience extracellular flux assays. Effects of 1,25D on
      GLUL/GS expression and glutamine oxidation were retained in human mammary
      epithelial (HME) cells that express SV-40 (HME-LT cells) but not in those that
      express SV-40 and oncogenic H-Ras (HME-PR cells). Furthermore, HME-PR cells
      exhibited glutamine independence and expressed constitutively high levels of
      GLUL/GS, which were unaffected by 1,25D. Collectively, these data suggest that
      1,25D alters glutamine availability, dependence, and metabolism in nontransformed
      and preneoplastic mammary epithelial cells in association with cell cycle arrest.

PMID- 29029016
TI  - diffuStats: an R package to compute diffusion-based scores on biological
      networks.
AB  - Summary: Label propagation and diffusion over biological networks are a common
      mathematical formalism in computational biology for giving context to molecular
      entities and prioritizing novel candidates in the area of study. There are
      several choices in conceiving the diffusion process-involving the graph kernel,
      the score definitions and the presence of a posterior statistical normalization
      which have an impact on the results. This manuscript describes diffuStats, an R
      package that provides a collection of graph kernels and diffusion scores, as well
      as a parallel permutation analysis for the normalized scores, that eases the
      computation of the scores and their benchmarking for an optimal choice.
      Availability and implementation: The R package diffuStats is publicly available
      in Bioconductor, https://bioconductor.org, under the GPL-3 license. Contact:
      sergi.picart@upc.edu. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29029017
TI  - Region-Specific Suppression of Hypothalamic Responses to Insulin To Adapt to
      Elevated Maternal Insulin Secretion During Pregnancy.
AB  - As part of the adaptation of maternal glucose regulation during pregnancy to
      ensure glucose provision to the fetus, maternal insulin concentrations become
      elevated. However, increased central actions of insulin, such as suppression of
      appetite, would be maladaptive during pregnancy. We hypothesized that central
      nervous system targets of insulin become less responsive during pregnancy to
      prevent overstimulation by the increased circulating insulin concentrations. To
      test this hypothesis, we have measured insulin-induced phosphorylation of Akt
      (pAkt) in specific hypothalamic nuclei as an index of hypothalamic insulin
      responsiveness. Despite higher endogenous insulin concentrations following
      feeding, arcuate nucleus pAkt levels were significantly lower in the pregnant
      group compared with the nonpregnant group. In response to an
      intracerebroventricular injection of insulin, insulin-induced pAkt was
      significantly reduced in the arcuate nucleus and ventromedial nucleus of pregnant
      rats compared with nonpregnant rats. Similar levels of insulin receptor beta and
      PTEN, a negative regulator of the phosphoinositide 3-kinase/Akt pathway, were
      detected in hypothalamic areas of nonpregnant and pregnant rats. In the
      ventromedial nucleus, however, levels of phosphorylated PTEN were significantly
      lower in pregnancy, suggesting that reduced inactivation of PTEN may contribute
      to the attenuated insulin signaling in this area during pregnancy. In conclusion,
      these results demonstrate region-specific changes in responsiveness to insulin in
      the hypothalamus during pregnancy that may represent an adaptive response to
      minimize the impact of elevated circulating insulin on the maternal brain.

PMID- 29029018
TI  - Corrigendum to 'Chewing 50 times per bite could help to resume oral feeding on
      the first postoperative day following minimally invasive oesophagectomy' [Eur J
      Cardiothorac Surg 2017].

PMID- 29029020
TI  - The Endometrial Polarity Paradox: Differential Regulation of Polarity Within
      Secretory-Phase Human Endometrium.
AB  - A major cause of infertility in normal and assisted reproduction cycles is
      failure of the endometrium to undergo appropriate changes during the secretory
      phase of the menstrual cycle as it acquires receptivity for an implanting
      blastocyst. Current dogma states that loss of epithelial polarity in the luminal
      epithelial cells, the point of first contact between maternal endometrium and
      blastocyst, may facilitate embryo implantation. Loss of polarity is likely an
      important change during the secretory phase to overcome mutual repulsion between
      otherwise polarized epithelial surfaces. Although "plasma membrane
      transformation" describes morphological/molecular alterations associated with
      loss of polarity, direct measures of polarity have not been investigated.
      Transepithelial resistance, a proxy measure of polarity, was downregulated in
      endometrial epithelial (ECC-1) cells by combined estrogen/progestin, mimicking
      the hormonal milieu of the secretory phase. Examination of defined polarity
      markers within human endometrium throughout the menstrual cycle identified
      downregulation of atypical protein kinase C, Stardust, Crumbs, and Scribble
      within the luminal-epithelial layer, with upregulation of Scribble within the
      stromal compartment as the menstrual cycle progressed from the estrogen-dominated
      proliferative to progesterone-dominated secretory phase. Epithelial (ECC-1)
      Scribble expression was downregulated in vitro by combined estrogen/progestin and
      estrogen/progestin/human chorionic gonadotropin treatment, whereas knockdown of
      Scribble in these cells enhanced "embryo" (trophectodermal spheroid) adhesion. In
      contrast, Scribble was upregulated within decidualized primary human endometrial
      stromal cells, with decidualization downregulated upon Scribble knockdown. These
      data highlight an important contribution of polarity modulation within the human
      endometrium, likely important for receptivity. Clinical investigations examining
      how polarity may be modulated in the infertile endometrium may facilitate
      fertility.

PMID- 29029021
TI  - Aetiological heterogeneity of head and neck squamous cell carcinomas: the role of
      human papillomavirus infections, smoking and alcohol.
AB  - Tobacco and alcohol consumption are the main risk factors for head and neck
      squamous cell carcinoma (HNSCC). In addition, human papillomavirus (HPV)
      infection plays a causal role in oropharyngeal cancer (OPC), a subset of HNSCC.
      We assessed the independent effects of tobacco, alcohol and HPV infection on OPC
      risk in the head and neck cancer (HeNCe) Life study, a hospital-based case
      control study of HNSCC with frequency-matched controls by age and sex from four
      Montreal hospitals. Interviewers collected information on socio-demographic and
      behavioural factors. We tested exfoliated oral cells for HPV DNA by polymerase
      chain reaction (PCR). We included only OPC cases (n = 188) and controls (n = 427)
      without missing values for HPV, smoking or alcohol. We examined associations by
      estimating odds ratios (ORs) and corresponding 95% confidence intervals (CI)
      using unconditional logistic regression. Smoking (OR = 1.90, 95% CI: 1.04-3.45)
      and alcohol (OR = 2.74, 95% CI: 1.45-5.15) were associated with an increased risk
      of OPC independent of HPV status. Positivity for HPV 16 among heavy smokers and
      heavy alcohol users was associated with a 30.4-fold (95% CI: 8.94-103.26) and
      18.6-fold (95% CI: 5.75-60.13) elevation in risk of OPC relative to participants
      who were HPV negative, respectively. Moreover, the combined effect of heavy
      smoking and alcohol comsumption with HPV 16 infection substantially increased OPC
      risk (OR = 48.76, 95% CI: 15.83-150.17) and (OR = 50.60, 95% CI: 15.96-160.40),
      respectively. Our results support the independent roles of smoking, alcohol and
      HPV infection in OPC risk and a possible combined effect. Efforts should be made
      to tackle these major risk factors simultaneously.

PMID- 29029019
TI  - Combined Loss of EAF2 and p53 Induces Prostate Carcinogenesis in Male Mice.
AB  - Mutations in the p53 tumor suppressor are frequent in patients with castration
      resistant prostate cancer but less so in patients with localized disease, and
      patients who have Li-Fraumeni with germline p53 mutations do not have an
      increased incidence of prostate cancer, suggesting that additional molecular
      and/or genetic changes are required for p53 to promote prostate carcinogenesis.
      ELL-associated factor 2 (EAF2) is a tumor suppressor that is frequently
      downregulated in advanced prostate cancer. Previous studies have suggested that
      p53 binds to EAF2, providing a potential mechanism for their functional
      interactions. In this study, we tested whether p53 and EAF2 could functionally
      interact in prostate cancer cells and whether concurrent inactivation of p53 and
      EAF2 could promote prostate carcinogenesis in a murine knockout model. Endogenous
      p53 coprecipitated with EAF2 in prostate cancer cells, and deletion mutagenesis
      indicated that this interaction was mediated through the C terminus of EAF2 and
      the DNA binding domain of p53. Concurrent knockdown of p53 and EAF2 induced an
      increase in proliferation and migration in cultured prostate cancer cells, and
      conventional p53 and EAF2 knockout mice developed prostate cancer. In human
      prostate cancer specimens, concurrent p53 nuclear staining and EAF2
      downregulation was associated with high Gleason score. These findings suggest
      that EAF2 and p53 functionally interact in prostate tumor suppression and that
      simultaneous inactivation of EAF2 and p53 can drive prostate carcinogenesis.

PMID- 29029022
TI  - Functional Characterization of MicroRNA-27a-3p Expression in Human Polycystic
      Ovary Syndrome.
AB  - The goal of this study was to characterize the function of microRNA-27a-3p (miR
      27a-3p) in polycystic ovary syndrome (PCOS). miR-27a-3p expression was analyzed
      in excised granulosa cells (GCs) from 21 patients with PCOS and 12 normal
      patients undergoing in vitro fertilization cycle treatments and in 17 nontreated
      cuneiform ovarian resection PCOS samples and 13 control ovarian samples from
      patients without PCOS. We found that the expression of miR-27a-3p was
      significantly increased in both excised GCs and the ovaries of patients with PCOS
      compared with the controls. Insulin treatment of the human granulosa-like tumor
      cell line (KGN) resulted in decreased downregulated expression of miR-27a-3p, and
      this effect appeared to be mediated by signal transducer and activator of
      transcription STAT1 and STAT3. The overexpression of miR-27a-3p in KGN cells
      inhibited SMAD5, which in turn decreased cell proliferation and promoted cell
      apoptosis. After KGN cells were stimulated with insulin for 48 hours, there was
      increased expression of SMAD5 protein and decreased apoptosis. Additionally,
      knockdown/overexpression of SMAD5 in KGN cells reduced/increased cell number and
      promoted/inhibited cell apoptosis. Insulin-stimulated primary GCs isolated from
      patients with PCOS, in contrast to normal GCs or KGN cells, did not exhibit
      decreased miR-27a-3p expression. The differences in the expression levels in KGN
      cells and human PCOS GCs are likely explained by increased miR-27a-3p expression
      in the GCs caused by insulin resistance in PCOS. Taken together, our data
      provided evidence for a functional role of miR-27a-3p in the GCs' dysfunction
      that occurs in patients with PCOS.

PMID- 29029023
TI  - Comprehensive evaluation of the effectiveness and safety of balloon pulmonary
      angioplasty for inoperable chronic thrombo-embolic pulmonary hypertension: long
      term effects and procedure-related complications.
AB  - Aims: Although balloon pulmonary angioplasty (BPA) improves haemodynamics and
      short-term prognosis in patients with inoperable chronic thrombo-embolic
      pulmonary hypertension (CTEPH), the long-term effects of BPA, and procedure
      related complications remain to be fully elucidated. Methods and results: From
      July 2009 to October 2016, we performed a total of 424 BPA sessions in 84
      consecutive patients with inoperable CTEPH. We used 3D reconstructed computed
      tomography to determine target lesions of pulmonary arteries and optical computed
      tomography to select balloon size, if needed. In 77 patients (92%) who completed
      the BPA treatment [65 +/- 14 (SD) years-old, male/female 14/63], haemodynamics
      and exercise capacity were examined at 6 months after last BPA and in the chronic
      phase [>12 months after first BPA, 31 (20, 41) months]. The BPA treatment
      significantly improved mean pulmonary arterial pressure (38 +/- 10 to 25 +/- 6
      mmHg), pulmonary vascular resistance (7.3 +/- 3.2 to 3.8 +/- 1.0 Wood units), and
      6-minute walk distance (380 +/- 138 to 486 +/- 112 m) (all P < 0.01), and the
      improvements persisted throughout the follow-up period (43 +/- 27 months) (N =
      53). In the 424 sessions, haemoptysis was noted in 60 sessions (14%), and non
      invasive positive pressure ventilation (NPPV) was used to treat haemoptysis
      and/or hypoxemia in 33 sessions (8%). Furthermore, 5-year survival was 98.4%
      (only one patient died of colon cancer) with no peri-procedural death.
      Conclusion: These results indicate that BPA improves haemodynamics and exercise
      capacity in inoperable CTEPH patients with acceptable complication rate and that
      the beneficial haemodynamic effects of BPA persist for years with resultant good
      long-term prognosis.

PMID- 29029024
TI  - DiversePathsJ: diverse shortest paths for bioimage analysis.
AB  - Motivation: We introduce a formulation for the general task of finding diverse
      shortest paths between two end-points. Our approach is not linked to a specific
      biological problem and can be applied to a large variety of images thanks to its
      generic implementation as a user-friendly ImageJ/Fiji plugin. It relies on the
      introduction of additional layers in a Viterbi path graph, which requires slight
      modifications to the standard Viterbi algorithm rules. This layered graph
      construction allows for the specification of various constraints imposing
      diversity between solutions. Results: The software allows obtaining a collection
      of diverse shortest paths under some user-defined constraints through a
      convenient and user-friendly interface. It can be used alone or be integrated
      into larger image analysis pipelines. Availability and implementation:
      http://bigwww.epfl.ch/algorithms/diversepathsj. Contact: michael.unser@epfl.ch or
      fred.hamprecht@iwr.uni-heidelberg.de. Supplementary information: Supplementary
      data are available at Bioinformatics online.

PMID- 29029025
TI  - Insulin-Deficient Mouse beta-Cells Do Not Fully Maturebut Can Be Remedied Through
      Insulin Replacementby Islet Transplantation.
AB  - Insulin receptor (IR) insufficiency in beta-cells leads to impaired insulin
      secretion and reduced beta-cell hyperplasia in response to hyperglycemia.
      Selective IR deficiency in beta-cells in later embryological development may lead
      to compensatory beta-cell hyperplasia. Although these findings suggest insulin
      signaling on the beta-cell is important for beta-cell function, they are
      confounded by loss of signaling by the insulinlike growth factors through the IR.
      To determine whether insulin itself is necessary for beta-cell development and
      maturation, we performed a characterization of pancreatic islets in mice with
      deletions of both nonallelic insulin genes (Ins1-/-Ins2-/-). We immunostained
      neonatal Ins1-/-Ins2-/- and Ins1+/+Ins2+/+ pancreata and performed quantitative
      polymerase chain reaction on isolated neonatal islets. Insulin-deficient islets
      had reduced expression of factors normally expressed in maturing beta-cells,
      including muscoloaponeurotic fibrosarcoma oncogene homolog A, homeodomain
      transcription factor 6.1, and glucose transporter 2. Ins1-/-Ins2-/-beta-cells
      expressed progenitor factors associated with stem cells or dedifferentiated beta
      cells, including v-myc avian myolocytomatosis viral oncogene lung carcinoma
      derived and homeobox protein NANOG. We replaced insulin by injection or islet
      transplantation to keep mice alive into adulthood to determine whether insulin
      replacement was sufficient for the completed maturation of insulin-deficient beta
      cells. Short-term insulin glargine (Lantus(r)) injections partially rescued the
      beta-cell phenotype, whereas long-term replacement of insulin by isogenic islet
      transplantation supported the formation of more mature beta-cells. Our findings
      suggest that tightly regulated glycemia, insulin species, or other islet factors
      are necessary for beta-cell maturation.

PMID- 29029026
TI  - Long-segment pulmonary artery resection to avoid pneumonectomy: long-term results
      after prosthetic replacement.
AB  - OBJECTIVES: Resection of a long pulmonary artery (PA) segment infiltrated by
      tumour and reconstruction by conduit interposition or wide patch is a challenging
      but feasible option to avoid pneumonectomy. Our goal was to report the long-term
      results of our experience with this type of operation using various techniques
      and materials. METHODS: Between 1991 and 2015, 24 patients underwent sleeve
      resection of a long PA segment or extended resection (>2.5 cm) of 1 aspect of the
      circumference of the PA associated with lobectomy for centrally located lung
      cancer. Materials used for conduit reconstruction (20 patients) included
      pulmonary vein in 12 patients, autologous pericardium in 4, porcine pericardium
      in 3 and bovine pericardium in 1. Patches used in 4 patients consisted of porcine
      pericardium (2 patients) and pulmonary vein (2 patients). RESULTS: Twenty-three
      patients underwent left upper lobectomy without associated bronchoplasty. One
      patient underwent bronchovascular left upper sleeve lobectomy. The postoperative
      morbidity rate was 29.1%. No complications related to the reconstructive
      procedure occurred. There were no postoperative deaths. Complete patency of the
      reconstructed PA was shown in all patients by postoperative contrast computed
      tomography performed every 6 months. Pathological tumour stage ranged from I to
      IIIA. Five-year overall survival and disease-free survival rates were 69.9% and
      52.7%, respectively, at a median follow-up of 41 months. CONCLUSIONS: Resection
      of the long PA segment followed by conduit or wide patch reconstruction is a
      feasible, safe and effective option to avoid pneumonectomy. Different biological
      materials can be used to provide adequate tissue characteristics; the choice is
      made on a case-by-case basis. Long-term results confirm the oncological
      reliability of this operation.

PMID- 29029027
TI  - Patent protection for microbial technologies.
AB  - Microbial technologies often serve as the basis of fundamental research tools in
      molecular biology. These present a variety of ethical, legal and social issues
      concerning their patenting. This commentary presents several case studies of
      these issues across three major microbiological tools: CRISPR, viral vectors and
      antimicrobial resistance drugs. It concludes that the development of these
      technologies-both scientifically and commercially-depend, in part, on the patent
      regime available for each, and researchers' willingness to enforce those patents
      against others.

PMID- 29029028
TI  - Intralobar pulmonary sequestration with an aortic aneurysm.

PMID- 29029030
TI  - Outcomes of surgery for infective endocarditis: a single-centre experience of 801
      patients.
AB  - OBJECTIVES: Infective endocarditis (IE) remains a life-threatening disease,
      despite the improvement in diagnostic and therapeutic measures. We reviewed our
      outcomes for all adults who underwent surgery for endocarditis at our centre.
      METHODS: Between January 1995 and December 2013, 801 patients [586 men (73%)]
      underwent surgery for IE. Mean age was 60 +/- 14.7 years. Native endocarditis
      (NE) was present in 372 patients (46%), and 379 (47%) patients had active IE. The
      mean follow-up period was 4.6 +/- 4.75 years (maximum 20 years). RESULTS: Single
      valve endocarditis was present in 551 (69%) patients (392 aortic and 159 mitral).
      Multivalve involvement was present in 250 (31%) patients. Preoperative stroke was
      present in 149 (19%) patients, while 62 (8%) patients were on dialysis prior to
      surgery. Valve repair was possible in 122 (15%) patients, while 679 (85%)
      patients underwent valve replacement. Mechanical valves were used in 312 (39%)
      patients. Aortic homografts were used in 84 (10%) patients. Early mortality
      occurred in 64 (8%) patients. Overall survival at 5, 10 and 20 years was 68%, 45%
      and 8.4%, respectively. Postoperative stroke occurred in 16 (2%) patients, while
      59 (7%) patients required new dialysis postoperatively. Multivariate analysis
      revealed active IE (P = 0.002), preoperative dialysis (P = 0.007), previous
      coronary artery bypass grafting (P = 0.001), root abscess (P = 0.006) and
      tricuspid valve or multivalve involvement (P = 0.002) to be predictors of early
      mortality. The need for dialysis (P < 0.001), previous coronary artery bypass
      grafting (P < 0.001) and mitral valve (P = 0.002) and tricuspid valve/multivalve
      involvement (P < 0.001) were significant predictors of late mortality.
      CONCLUSIONS: Active IE is associated with high perioperative mortality especially
      with multivalve and aortic root involvement. Preoperative stroke has no impact on
      perioperative mortality. Long-term survival for those who survived the immediate
      postoperative period is satisfactory, and mechanical valves are associated with
      the best long-term survival.

PMID- 29029029
TI  - A manifesto for cardiovascular imaging: addressing the human factor.
AB  - Our use of modern cardiovascular imaging tools has not kept pace with their
      technological development. Diagnostic errors are common but seldom investigated
      systematically. Rather than more impressive pictures, our main goal should be
      more precise tests of function which we select because their appropriate use has
      therapeutic implications which in turn have a beneficial impact on morbidity or
      mortality. We should practise analytical thinking, use checklists to avoid
      diagnostic pitfalls, and apply strategies that will reduce biases and avoid
      overdiagnosis. We should develop normative databases, so that we can apply
      diagnostic algorithms that take account of variations with age and risk factors
      and that allow us to calculate pre-test probability and report the post-test
      probability of disease. We should report the imprecision of a test, or its
      confidence limits, so that reference change values can be considered in daily
      clinical practice. We should develop decision support tools to improve the
      quality and interpretation of diagnostic imaging, so that we choose the single
      best test irrespective of modality. New imaging tools should be evaluated
      rigorously, so that their diagnostic performance is established before they are
      widely disseminated; this should be a shared responsibility of manufacturers with
      clinicians, leading to cost-effective implementation. Trials should evaluate
      diagnostic strategies against independent reference criteria. We should exploit
      advances in machine learning to analyse digital data sets and identify those
      features that best predict prognosis or responses to treatment. Addressing these
      human factors will reap benefit for patients, while technological advances
      continue unpredictably.

PMID- 29029031
TI  - Impact of Field Densities of the Naturalized Defoliator Caloptilia triadicae
      (Lepidoptera: Gracillariidae) on the Invasive Weed Chinese Tallowtree.
AB  - Chinese tallowtree, Triadica sebifera (L.) Small (Euphoriaceae), is one of the
      most aggressive weeds of coastal wetlands and forests of the southeastern United
      States. The lack of specialist herbivores in the invaded range may be one of the
      factors that contribute to the invasive nature of this weed. Chinese tallowtree
      has been the target of a classical biological control project since 2006. Several
      herbivore species are being tested for biological control of Chinese tallowtree.
      Concurrently, an adventive herbivore, Caloptilia triadicae Davis (Lepidoptera:
      Gracillariidae), was found feeding on Chinese tallowtree in the southeastern
      United States in 2004 and now occurs throughout the invaded range. Field
      populations of C. triadicae from two sites caused extensive mining damage to the
      Chinese tallowtree leaves. The greatest damage occurred after 30 d of exposure to
      C. triadicae in the herbivory treatment and amounted to about 25-30 leaf mines
      (early instars) and leaf rolls (late instars) per plant. Insecticide-treated
      plants had atmost 5-10 leaf mines and rolls per plant. Despite this difference,
      plant growth in height, number of new branches, and leaves did not differ
      significantly from plants protected from herbivory. Analysis of harvested plant
      results suggested that, in general, herbivory had little impact on biomass.
      However, there was a slight reduction in trunk weights in the unrestriced
      herbivory treatment compared with the insecticide-treated plants. Although this
      study exposed experimental plants to only 60 d of herbivory, these results
      suggested that C. triadicae alone will not exert sufficient control of invasive
      populations of Chinese tallowtree. Furthermore, they indicated that continued
      development of biological control agents that target Chinese tallowtree are
      needed.

PMID- 29029032
TI  - FOXA1 expression is a strong independent predictor of early PSA recurrence in ERG
      negative prostate cancers treated by radical prostatectomy.
AB  - FOXA1 (Fork-head box protein A1, HNF-3a) is a transcription factor involved in
      androgen signaling with relevance for lineage-specific gene expression of the
      prostate. The expression was analyzed by immunohistochemistry on a tissue
      microarray containing 11152 prostate cancer specimens. Results were compared with
      tumor phenotype, biochemical recurrence, androgen receptor expression, ETS
      related gene (ERG) status and other recurrent genomic alterations. FOXA1
      expression was detectable in 97.6% of 8227 interpretable cancers and considered
      strong in 28.5%, moderate in 46.2% and weak in 22.9% of cases. High FOXA1
      expression was associated with TMPRSS2:ERG rearrangement and ERG expression (P <
      0.0001). High FOXA1 expression was linked to high Gleason grade, advanced
      pathological tumor (pT) stage and early PSA recurrence in ERG negative cancers (P
      < 0.0001), while these associations were either weak or absent in ERG positive
      cancers. In ERG negative cancers, the prognostic role of FOXA1 expression was
      independent of Gleason grade, pathological tumor stage, lymph node stage,
      surgical margin status and preoperative PSA. Independent prognostic value became
      even more evident if the analysis was limited to preoperatively available
      features such as biopsy Gleason grade, preoperative PSA, cT stage and FOXA1
      expression (P < 0.0001). Within ERG negative cancers, FOXA1 expression was also
      strongly associated with PTEN and 5q21 deletions (P < 0.0001). High expression of
      FOXA1 is an independent prognostic parameter in ERG negative prostate cancer.
      Thus, FOXA1 measurement might provide clinically useful information in prostate
      cancer.

PMID- 29029034
TI  - Ten-year experience of endocardial linear infarct exclusion technique for
      ischaemic cardiomyopathy.
AB  - OBJECTIVES: To report the mid-term results of our surgical ventricular
      restoration procedure, called the endocardial linear infarct exclusion technique
      (ELIET), for ischaemic cardiomyopathy. METHODS: From 2006 to 2015, 43 consecutive
      patients who underwent surgical ventricular restoration with ELIET for ischaemic
      cardiomyopathy were retrospectively analysed. RESULTS: The mean age of patients
      at surgery was 65.3 +/- 9.2 years and EuroSCORE II was 13.7 +/- 12.0% (median
      9.3%). The mean number of distal anastomoses of coronary artery bypass was 2.8 +/
      1.5. A concomitant mitral procedure was performed in 58.1% of patients. The
      hospital mortality rate was 11.6% (5 patients). The ejection fraction was
      improved from 24.1 +/- 9.2% to 31.7 +/- 8.2% in 2 weeks after surgery. The end
      systolic left ventricular volume index was effectively reduced, irrespective of
      performing a concomitant mitral procedure (reduction rate, ELIET: 35.6% vs ELIET
      + mitral: 39.2%). After ELIET, the sphericity index of the left ventricle did not
      worsen, and the conicity index was significantly improved. The 5-year estimated
      rates of survival and freedom from cardiac events were 71.3 +/- 7.9 and 61.1 +/-
      8.3%, respectively. A concomitant mitral procedure was significantly associated
      with cardiac events based on univariate Cox hazard analysis. CONCLUSIONS: This
      study showed that ELIET can effectively reduce the ventricular volume and create
      an ellipsoidal left ventricle.

PMID- 29029035
TI  - Long-term survival and causes of death in patients with ST-elevation acute
      coronary syndrome without obstructive coronary artery disease.
AB  - Aims: We aimed to study survival and causes of death in patients with ST
      elevation acute coronary syndrome (STE-ACS) with and without obstructive coronary
      artery disease (CAD). Methods and results: We included 4793 consecutive patients
      with STE-ACS triaged for acute coronary angiography at a large cardiac invasive
      centre (2009-2014). Of these, 88% had obstructive CAD (stenosis >=50%), 6% had
      non-obstructive CAD (stenosis 1-49%), and 5% had normal coronary arteries.
      Patients without obstructive CAD were younger and more often female with fewer
      cardiovascular risk factors. Median follow-up time was 2.6 years. Compared with
      patients with obstructive CAD, the short-term hazard of death (<=30 days) was
      lower in both patients with non-obstructive CAD [hazard ratio (HR) 0.49, 95%
      confidence interval (CI) 0.27-0.89, P = 0.018] and normal coronary arteries (HR
      0.31, 95% CI 0.11-0.83, P = 0.021). In contrast, the long-term hazard of death
      (>30 days) was similar in patients with non-obstructive CAD (HR 1.15, 95% CI 0.77
      1.72, P = 0.487) and higher in patients with normal coronary arteries (HR 2.44,
      95% CI 1.58-3.76, P < 0.001), regardless of troponin levels. Causes of death were
      cardiovascular in 70% of patients with obstructive CAD, 38% with non-obstructive
      CAD, and 32% with normal coronary arteries. Finally, patients without obstructive
      CAD had lower survival compared with an age and sex matched general population.
      Conclusions: STE-ACS patients without obstructive CAD had a long-term risk of
      death similar to or higher than patients with obstructive CAD. Causes of death
      were less often cardiovascular. This suggests that STE-ACS patients without
      obstructive CAD warrant medical attention and close follow-up.

PMID- 29029036
TI  - Intracellular superoxide level controlled by manganese superoxide dismutases
      affects trichothecene production in Fusarium graminearum.
AB  - The intracellular superoxide level is a clue to clarification of the regulatory
      mechanism for mycotoxin production in Fusarium graminearum. In this study, we
      focused on two manganese superoxide dismutases (SODs) of the fungus, FgSOD2 and
      FgSOD3, to investigate the relationship of the superoxide level to trichothecene
      production. Recombinant FgSOD2 and FgSOD3 showed SOD activity, and they were
      localized mainly in the mitochondria and cytoplasm, respectively. Trichothecene
      production and mRNA levels of Tri5 and Tri6, which encode a trichothecene
      biosynthetic enzyme and a key regulator of trichothecene production,
      respectively, were greatly reduced in gene-deletion mutants of FgSod2 and FgSod3
      (DeltaFgSod2 and DeltaFgSod3). Significant increases in the cytosolic and
      mitochondrial superoxide levels were observed in DeltaFgSod2 and DeltaFgSod3,
      respectively. These results suggested that the cellular superoxide level affects
      trichothecene production in F. graminearum.

PMID- 29029037
TI  - Functional variants in the low-density lipoprotein receptor gene are associated
      with clear cell renal cell carcinoma susceptibility.
AB  - Recent studies indicate that abnormal levels of low-density lipoprotein (LDL),
      which is an important component of dyslipidaemia, are associated with alterations
      to cancer risk, including that of renal cell carcinoma (RCC). Single nucleotide
      polymorphisms at microRNA-binding sites contribute to cancer susceptibility and
      progression by affecting the messenger RNA (mRNA) function of target genes. In
      this case-control study, we examined the frequency of six potentially functional
      single nucleotide polymorphisms in the LDL receptor gene (LDLR) in 1004 clear
      cell RCC (ccRCC) patients and 1065 cancer-free subjects. Logistic regression
      analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs). The
      association between genetic variants and levels of LDLR mRNA and protein was also
      evaluated. Compared with the CC genotype, multivariate logistic regression
      analysis showed that the LDLR rs2738464 variant GG genotype was associated with a
      significantly decreased ccRCC risk (P = 0.002, OR: 0.605, 95% CI: 0.439-0.833).
      Further functional experiments showed that the rs2738464 variant G allele
      affected miR-330 regulation of the LDLR 3'-untranslated region (UTR), increasing
      LDLR mRNA levels in patient kidney tissues. These findings suggest that LDLR
      rs2738464 may affect the affinity of miR-330 binding to the LDLR 3'-UTR, thus
      regulating LDLR expression and contributing to ccRCC risk.

PMID- 29029033
TI  - Trial Evaluating Ambulatory Therapy of Travelers' Diarrhea (TrEAT TD) Study: A
      Randomized Controlled Trial Comparing 3 Single-Dose Antibiotic Regimens With
      Loperamide.
AB  - Background: Recommended treatment for travelers' diarrhea includes the
      combination of an antibiotic, usually a fluoroquinolone or azithromycin, and
      loperamide for rapid resolution of symptoms. However, adverse events, postdose
      nausea with high-dose azithromycin, effectiveness of single-dose rifaximin, and
      emerging resistance to front-line agents are evidence gaps underlying current
      recommendations. Methods: A randomized, double-blind trial was conducted in 4
      countries (Afghanistan, Djibouti, Kenya, and Honduras) between September 2012 and
      July 2015. US and UK service members with acute watery diarrhea were randomized
      and received single-dose azithromycin (500 mg; 106 persons), levofloxacin (500
      mg; 111 persons), or rifaximin (1650 mg; 107 persons), in combination with
      loperamide (labeled dosing). The efficacy outcomes included clinical cure at 24
      hours and time to last unformed stool. Results: Clinical cure at 24 hours
      occurred in 81.4%, 78.3%, and 74.8% of the levofloxacin, azithromycin, and
      rifaximin arms, respectively. Compared with levofloxacin, azithromycin was not
      inferior (P = .01). Noninferiority could not be shown with rifaximin (P = .07).
      At 48 and 72 hours, efficacy among regimens was equivalent (approximately 91% at
      48 and 96% at 72 hours). The median time to last unformed stool did not differ
      between treatment arms (azithromycin, 3.8 hours; levofloxacin, 6.4 hours;
      rifaximin, 5.6 hours). Treatment failures were uncommon (3.8%, 4.4%, and 1.9% in
      azithromycin, levofloxacin, and rifaximin arms, respectively) (P = .55). There
      were no differences between treatment arms with postdose nausea, vomiting, or
      other adverse events. Conclusions: Single-dose azithromycin, levofloxacin, and
      rifaximin with loperamide were comparable for treatment of acute watery diarrhea.
      Clinical Trial Registration: NCT01618591.

PMID- 29029038
TI  - Geographical distance and local environmental conditions drive the genetic
      population structure of a freshwater microalga (Bathycoccaceae; Chlorophyta) in
      Patagonian lakes.
AB  - The patterns and mechanisms underlying the genetic structure of microbial
      populations remain unresolved. Herein we investigated the role played by two non
      mutually exclusive models (i.e. isolation by distance and isolation by
      environment) in shaping the genetic structure of lacustrine populations of a
      microalga (a freshwater Bathycoccaceae) in the Argentinean Patagonia. To our
      knowledge, this was the first study to investigate the genetic population
      structure in a South American microorganism. Population-level analyses based on
      ITS1-5.8S-ITS2 sequences revealed high levels of nucleotide and haplotype
      diversity within and among populations. Fixation index and a spatially explicit
      Bayesian analysis confirmed the occurrence of genetically distinct microalga
      populations in Patagonia. Isolation by distance and isolation by environment
      accounted for 38.5% and 17.7% of the genetic structure observed, respectively,
      whereas together these models accounted for 41% of the genetic differentiation.
      While our results highlighted isolation by distance and isolation by environment
      as important mechanisms in driving the genetic population structure of the
      microalga studied, none of these models (either alone or together) could explain
      the entire genetic differentiation observed. The unexplained variation in the
      genetic differentiation observed could be the result of founder events combined
      with rapid local adaptations, as proposed by the monopolisation hypothesis.

PMID- 29029039
TI  - The Effects of Audiovisual Inputs on Solving the Cocktail Party Problem in the
      Human Brain: An fMRI Study.
AB  - At cocktail parties, our brains often simultaneously receive visual and auditory
      information. Although the cocktail party problem has been widely investigated
      under auditory-only settings, the effects of audiovisual inputs have not. This
      study explored the effects of audiovisual inputs in a simulated cocktail party.
      In our fMRI experiment, each congruent audiovisual stimulus was a synthesis of 2
      facial movie clips, each of which could be classified into 1 of 2 emotion
      categories (crying and laughing). Visual-only (faces) and auditory-only stimuli
      (voices) were created by extracting the visual and auditory contents from the
      synthesized audiovisual stimuli. Subjects were instructed to selectively attend
      to 1 of the 2 objects contained in each stimulus and to judge its emotion
      category in the visual-only, auditory-only, and audiovisual conditions. The
      neural representations of the emotion features were assessed by calculating
      decoding accuracy and brain pattern-related reproducibility index based on the
      fMRI data. We compared the audiovisual condition with the visual-only and
      auditory-only conditions and found that audiovisual inputs enhanced the neural
      representations of emotion features of the attended objects instead of the
      unattended objects. This enhancement might partially explain the benefits of
      audiovisual inputs for the brain to solve the cocktail party problem.

PMID- 29029041
TI  - Long-Term Effects of Berberis thunbergii (Ranunculales: Berberidaceae) Management
      on Ixodes scapularis (Acari: Ixodidae) Abundance and Borrelia burgdorferi
      (Spirochaetales: Spirochaetaceae) Prevalence in Connecticut, USA.
AB  - Japanese barberry (Berberis thunbergii de Candolle; Ranunculales: Berberidaceae)
      is an exotic invasive shrub that escaped cultivation in the United States and is
      now permanently established in many eastern and midwestern states. This study
      examined the long-term impacts of Japanese barberry management on blacklegged
      tick (Ixodes scapularis Say; Acari: Ixodidae) abundances and associated
      prevalence of Borrelia burgdorferi (Johnson, Schmid, Hyde, Steigerwalt, and
      Brenner; Spirochaetales: Spirochaetaceae), the etiologic agent of Lyme disease.
      At six locations across Connecticut, adult I. scapularis were sampled for up to
      10 yr. At each location, we sampled an area where barberry infestations were
      unmanipulated, adjacent areas where barberry was virtually nonexistent, and areas
      where barberry was managed utilizing a variety of techniques. Barberry management
      reduced B. burgdorferi-infected adult I. scapularis (BBIAIS) abundances (191/ha
      +/- 64 SE) over 6 yr to statistically indifferent from that of no barberry areas
      (140/ha +/- 47 SE; P = 0.080) and significantly less than intact barberry stands
      (458/ha +/- 80 SE; P = 0.026). Over 9 yr, BBIAIS abundances in managed barberry
      remained lower than intact barberry stands (P = 0.037), but increased to be
      significantly greater than no barberry areas (P = 0.007) as cover increased over
      time. Longer-term data further document that Japanese barberry infestations are
      favorable habitat for I. scapularis. Control of Japanese barberry and other
      invasives should be at least on a 5-yr rotation to maintain low levels of
      invasive cover and eliminate humidity refugia to expose juvenile I. scapularis to
      more hostile environmental conditions in the interest of public health.

PMID- 29029042
TI  - Does pharmacokinetic/pharmacodynamic model-guided anaesthesia improve outcome
      after hip fracture surgery?

PMID- 29029040
TI  - Herbacetin suppresses cutaneous squamous cell carcinoma and melanoma cell growth
      by targeting AKT and ODC.
AB  - Herbacetin is a flavonol compound that is found in plants such as flaxseed and
      ramose scouring rush herb, it possesses a strong antioxidant capacity, and exerts
      anticancer effects on colon and breast cancer. However, the effect of herbacetin
      on skin cancer has not been investigated. Herein, we identified herbacetin as a
      dual V-akt murine thymoma viral oncogene homolog (AKT) and ornithine
      decarboxylase (ODC) inhibitor, and illustrated its anticancer effects in vitro
      and in vivo against cutaneous squamous cell carcinoma (SCC) and melanoma cell
      growth. To identify the direct target(s) of herbacetin, we screened several skin
      cancer-related protein kinases, and results indicated that herbacetin strongly
      suppresses both AKT and ODC activity. Results of cell-based assays showed that
      herbacetin binds to both AKT and ODC, inhibits TPA-induced neoplastic
      transformation of JB6 mouse epidermal cells, and suppresses anchorage-independent
      growth of cutaneous SCC and melanoma cells. The inhibitory activity of herbacetin
      was associated with markedly reduced NF-kappaB and AP1 reporter activity.
      Interestingly, herbacetin effectively attenuated TPA-induced skin cancer
      development and also exhibited therapeutic effects against solar-UV-induced skin
      cancer and melanoma growth in vivo. Our findings indicate that herbacetin is a
      potent AKT and ODC inhibitor that should be useful for preventing skin cancers.

PMID- 29029043
TI  - Degradation of the recalcitrant oil spill components anthracene and pyrene by a
      microbially driven Fenton reaction.
AB  - Oil spill components include a range of toxic saturated, aromatic and polar
      hydrocarbons, including pyrene and anthracene. Such contaminants harm natural
      ecosystems, adversely affect human health and negatively impact tourism and the
      fishing industries. Current physical, chemical and biological remediation
      technologies are often unable to completely remove recalcitrant oil spill
      components, which accumulate at levels greater than regulatory limits set by the
      Environmental Protection Agency. In the present study, a microbially driven
      Fenton reaction, previously shown to produce hydroxyl (HO * ) radicals that
      degrade chlorinated solvents and associated solvent stabilizers, was also found
      to degrade source zone concentrations of the oil spill components, pyrene (10
      MUM) and anthracene (1 MUM), at initial rates of 0.82 and 0.20 MUM h -1 ,
      respectively. The pyrene- and anthracene-degrading Fenton reaction was driven by
      the metal-reducing facultative anaerobe Shewanella oneidensis exposed to
      alternating aerobic and anaerobic conditions in the presence of Fe(III). Similar
      to the chlorinated solvent degradation system, the pyrene and anthracene
      degradation systems required neither the continual supply of exogenous H 2 O 2
      nor UV-induced Fe(III) reduction to regenerate Fe(II). The microbially driven
      Fenton reaction provides the foundation for the development of alternate ex situ
      and in situ oil and gas spill remediation technologies.

PMID- 29029044
TI  - Enhanced killing of Escherichia coli using a combination of polyhexamethylene
      biguanide hydrochloride and 1-bromo-3-chloro-5,5- dimethylimidazolidine-2,4
      dione.
AB  - The bactericidal activities of polyhexamethylene biguanide hydrochloride (PHMB),
      1-bromo-3-chloro-5,5-dimethylimidazolidine-2,4-dione (BCDMH) and the combination
      of the two (designated as PB) were compared using Escherichia coli as the test
      organism. PB exhibited strong bactericidal activity: 10 mg/L PHMB combined with 8
      mg/L BCDMH resulted in approximately 5.74 log10 reduction (LR), whereas 320 mg/L
      PHMB or 20 mg/L BCDMH was about 5.53 and 6.56 LR, respectively. Analyses using
      scanning electron microscopy, flow cytometry and atomic absorption spectroscopy
      indicated that PB, PHMB and BCDMH disrupted cell membranes and changed membrane
      structure and permeability, resulting in the leakage of intracellular soluble
      proteins and ions. PB exerted stronger effects on potassium and magnesium
      leakage, membrane potential and permeability than BCDMH did. PB caused less
      protein leakage than PHMB did. These results suggest that at a relatively low
      concentration, PB exhibited good bactericidal activity and physiological effect
      on E. coli.

PMID- 29029045
TI  - Revisiting the contribution of gene duplication of blaOXA-23 in carbapenem
      resistant Acinetobacter baumannii.

PMID- 29029046
TI  - Ammonia oxidisers in a non-nitrifying Brazilian savanna soil.
AB  - Low nitrification rates in Brazilian savanna (Cerrado) soils have puzzled
      researchers for decades. Potential mechanisms include biological inhibitors, low
      pH, low microbial abundance and low soil moisture content, which hinders
      microbial activity, including ammonia oxidation. Two approaches were used to
      evaluate these potential mechanisms: (i) manipulation of soil moisture and pH in
      microcosms containing Cerrado soil and (ii) assessment of nitrification
      inhibition in slurries containing mixtures of Cerrado soil and an actively
      nitrifying agricultural soil. Despite high ammonium concentration in Cerrado soil
      microcosms, little NO3- accumulation was observed with increasing moisture or pH,
      but in some Cerrado soil slurries, ammonia-oxidising archaea (AOA) amoA
      transcripts were detected after 14 days. In mixed soil slurries, the final NO3-
      concentration reflected the initial proportions of agricultural and Cerrado soils
      in the mixture, providing no evidence of nitrification inhibitors in Cerrado
      soil. AOA community denaturing gradient gel electrophoresis profiles were similar
      in the mixed and nitrifying soils. These results suggest that nitrification in
      Cerrado soils is not constrained by water availability, ammonium availability,
      low pH or biological inhibitors, and alternative potential explanations for low
      nitrification levels are discussed.

PMID- 29029048
TI  - General practitioners' perception of being a doctor in urban vs. rural regions in
      Germany - A focus group study.
AB  - Background: Inadequate recruitment numbers for GPs in rural regions give cause
      for concern. Working in rural regions is less attractive among medical students
      because of strong associations concerning a higher workload, restriction of
      privacy and demands exceeding their competences. We aimed to explore perceptions
      of GPs working in urban versus rural regions to contrast these prejudices.
      Methods: We conducted nine focus groups with GPs [female = 21, male = 44] from
      urban and rural regions, using a semi-structured guideline. Transcripts were
      content analyzed using deductive and inductive categories. Results: Urban GPs
      perceived themselves as a provider of medical services and rural GPs as being a
      medical companion. Compared to urban GPs, GPs from non-urban regions portray
      themselves more strongly as a family physician that accompanies patients 'from
      the cradle to the grave' and is responsible for the treatment of any medical
      issue. They emphasized their close relationship with their patients. Rural GPs
      establish a close relationship with their patients and considered this as
      beneficial for the treatment relationship. This aspect seems to play a
      subordinate role for urban GPs. Conclusions: GPs enjoy their work and the role
      they play in their patients' lives. Being a rural GP was described very
      positively. Greater emphasis should be made on positive aspects of being a GP in
      rural regions, e.g. by university lectures given by rural GPs, campaigns
      emphasizing the positive aspects of working as a GP [in rural regions], promotion
      of work placements or incentives for working in rural general practices.

PMID- 29029047
TI  - Community structure of rare methanogenic archaea: insight from a single
      functional group.
AB  - The rare biosphere, the low abundant microbial populations, is suggested to be a
      conserved way of microbial life. Here we conducted a molecular survey of rare
      methanogenic archaea in the environment targeting the mcrA gene in order to test
      if general concepts associated with the structure of the rare bacterial biosphere
      also apply to single functional groups. Similar to what is known about rare
      bacterial communities, the contribution of rare methanogens to the alpha
      diversity is much larger than to Bray-Curtis measures. Moreover, a similar core
      group of methanogens harbored by the abundant and rare communities suggests
      similar sources and environmental controls of both groups. Among the communities
      of different levels of rarity, the conditionally rare methanogenic taxa largely
      account for the overall community dynamics of the rare biosphere and likely enter
      the dominant community under favorable environmental conditions. In addition, we
      observed a positive correlation between the alpha diversity and the production of
      methane when the rare taxa were taken into account. This supports the concept
      that increasing microbial biodiversity enhances ecological function. The
      composition and environmental associations of the rare methanogenic biosphere
      allow us to conclude that rarity is a conserved way also for single functional
      groups.

PMID- 29029049
TI  - Intraoperative naloxone reduces remifentanil-induced postoperative hyperalgesia
      but not pain: a randomized controlled trial.
AB  - Background: Intraoperative use of a high-dose remifentanil may induce
      postoperative hyperalgesia. Low-dose naloxone can selectively reverse some
      adverse effects of opioids without compromising analgesia. We thus hypothesized
      that the intraoperative use of a high-dose remifentanil combined with a low-dose
      naloxone infusion reduces postoperative hyperalgesia compared with the use of
      remifentanil alone. Methods: Patients undergoing elective thyroid surgery were
      randomly assigned into one of three groups, depending on the intraoperative
      effect-site concentration of remifentanil, with or without a continuous infusion
      of naloxone: 4 ng ml-1 remifentanil with 0.05 MUg kg-1 h-1 naloxone in the high
      remifentanil with naloxone group, and 4 or 1 ng ml-1 remifentanil with a placebo
      in the high- or low-remifentanil groups, respectively. We measured the pain
      thresholds (primary outcome) to mechanical stimuli using von Frey filaments and
      incidence of hyperalgesia on the peri-incisional area 24 h after surgery. We also
      measured pain intensity, analgesic consumptions and adverse events up to 48 h
      after surgery. Results: The pain threshold presented as von Frey numbers [median
      (interquartile range)] was significantly lower in the high-remifentanil group
      (n=31) than in the high-remifentanil with naloxone (n=30) and the low
      remifentanil (n=30) groups [3.63 (3.22-3.84) vs 3.84 (3.76-4.00) vs 3.80 (3.69
      4.08), P=0.011]. The incidence of hyperalgesia was also higher in the high
      remifentanil group than in the other groups [21/31 vs 10/30 vs 9/30, P=0.005].
      Postoperative pain intensity, analgesic consumptions and adverse events were
      similar between groups. Conclusions: The intraoperative use of low-dose naloxone
      combined with high-dose remifentanil reduced postoperative hyperalgesia but not
      pain. Clinical trial registration: NCT02856087.

PMID- 29029050
TI  - Small-sized conduits in the right ventricular outflow tract in young children:
      bicuspidalized homografts are a good alternative to standard conduits.
AB  - OBJECTIVES: Downsizing a homograft (HG) through bicuspidalization has been used
      for more than 2 decades to overcome the shortage of small-sized conduits for
      reconstruction of the right ventricular outflow tract (RVOT) in young children.
      Our goal was to investigate the durability of bicuspidalized HGs compared with
      other small HGs. METHODS: A retrospective analysis of 93 conduits <=20 mm,
      implanted over 23 years, was performed. The end-points were survival, structural
      valve degeneration and conduit replacement. The conduits comprised 40 pulmonary
      HGs, 12 aortic HGs, 17 bicuspidalized HGs and 24 xenografts. RESULTS: The median
      age, mean conduit diameter and z-value at implantation were 1.4 (interquartile
      range 0.3-3) years, 16.5 +/- 2.7 mm and 2.8 +/- 1.3, respectively. Valve position
      was heterotopic in 59 patients and orthotopic in 34 patients. At a mean follow-up
      period of 7.6 +/- 5.9 years, the hospital survival rate was 89%. Freedom from
      explant at 5 and 10 years was 83 +/- 5% and 52 +/- 6%, respectively. Freedom from
      structural valve degeneration was 79 +/- 5% at 5 years and 47 +/- 6% at 10 years
      [68 +/- 8% for pulmonary HG, 42 +/- 16% for bicuspidalized HG, 31 +/- 15% for
      aortic HG and 20 +/- 9% for xenografts (log rank P < 0.001)]. Multivariable
      analysis indicated an increased risk for structural valve degeneration with
      smaller conduit size (hazard ratio 0.79, 95% confidence interval 0.67-0.94; P <
      0.008), extra-anatomic position (hazard ratio 2.71, 95% confidence interval 1.33
      5.50; P = 0.006) and the use of xenografts compared with non-downsized pulmonary
      HGs (hazard ratio 4.90, 95% confidence interval 2.23-10.76; P < 0.001).
      CONCLUSIONS: Appropriately sized pulmonary HGs remain the most durable option for
      a right ventricular outflow tract conduit in young children. However, when a
      small pulmonary HG is unavailable, bicuspidalization offers a valid alternative,
      preferable to xenograft conduits, at mid-term follow-up.

PMID- 29029052
TI  - Corrigendum to: Adenoviral intramyocardial VEGF-DDeltaNDeltaC gene transfer
      increases myocardial perfusion reserve in refractory angina patients: a phase
      I/IIa study with 1-year follow-up.

PMID- 29029051
TI  - Multilocus sequence typing and virulence genotyping of Streptococcus suis
      serotype 9 isolates revealed high genetic and virulence diversity.
AB  - Streptococcus suis is an important swine pathogen that can cause a variety of
      diseases. Streptococcus suis serotype 9 (SS9) is a prevalent serotype, but
      limited information is available. Here, we studied and compared 30 SS9 isolates,
      including 24 isolates from China between year 2004 and 2013, 5 isolates from
      Vietnam and a serotype reference isolate from Denmark. A multilocus sequence
      typing (MLST) analysis was performed to exploit the genetic relationships between
      those isolates. The phylogenetic tree based on the MLST data divides those
      isolates into two clades (I and II), revealing different evolutionary paths of
      collected strains. A virulence genotyping analysis was performed by detecting 23
      virulence-related genes; the clustering result also revealed two clusters (I and
      II), highly in accordance with MLST analysis result, showing that phylogenetic
      relatedness led to the presence of similar virulence genotypes. Murine model
      infection experiment was performed to assess the virulence of those strains in
      cluster I and cluster II, which displayed high virulence diversity even within a
      same cluster/ST. Notably, ST 243 could be regarded as an ST with high virulence
      potential in SS9. In conclusion, this study has revealed high genetic and
      virulence diversity in SS9 isolates.

PMID- 29029053
TI  - A 12-Year Follow-up on the Long-Term Effectiveness of the Quadrivalent Human
      Papillomavirus Vaccine in 4 Nordic Countries.
AB  - Background: The long-term effectiveness of the quadrivalent human papillomavirus
      (qHPV) vaccine was assessed by monitoring the combined incidence of cervical
      intraepithelial neoplasia (CIN2, CIN3), adenocarcinoma in situ (AIS), and
      cervical cancer related to HPV16 or HPV18. Methods: Women from Nordic countries
      of Denmark, Iceland, Norway, and Sweden who received a 3-dose regimen of the qHPV
      vaccine in the beginning of FUTURE II (Females United to Unilaterally Reduce
      Endo/Ectocervical Disease; V501-015, base study NCT00092534) are followed through
      different national registries. Effectiveness analyses were conducted
      approximately 2 years following completion of the base study and occur
      approximately every 2 years thereafter for 10 years (ie, 14 years from day 1 of
      the base study). Vaccine effectiveness against HPV16/18-related CIN2 or worse
      (CIN2+) was estimated by comparing the observed incidence with the expected
      incidence of CIN2+ in an unvaccinated cohort using historical registry data.
      Results: In the per-protocol population (2084 women) analysis of effectiveness
      after the first 12 years, there were no breakthrough cases of HPV16/18 CIN2+
      after 9437 person- years of follow-up. Statistical power was sufficient to
      conclude that qHPV vaccine effectiveness remains above 90% for at least 10 years.
      The number of person-years during the follow-up interval of 10-12 years is
      continuing to accrue and shows a trend toward continuing effectiveness of the
      vaccine during that period. Conclusion: The qHPV vaccine shows continued
      protection in women through at least 10 years, with a trend for continued
      protection through 12 years of follow-up. Clinical Trials Registration:
      NCT00092534. Study Identification: V501-015.

PMID- 29029055
TI  - Prognostic Models for 9-Month Mortality in Tuberculous Meningitis.
AB  - Background: Tuberculous meningitis (TBM) is the most severe form of
      extrapulmonary tuberculosis. We developed and validated prognostic models for 9
      month mortality in adults with TBM, with or without human immunodeficiency virus
      (HIV) infection. Methods: We included 1699 subjects from 4 randomized clinical
      trials and 1 prospective observational study conducted at 2 major referral
      hospitals in Southern Vietnam from 2001-2015. Modeling was based on multivariable
      Cox proportional hazards regression. The final prognostic models were validated
      internally and temporally and were displayed using nomograms and a Web-based app
      (https://thaole.shinyapps.io/tbmapp/). Results: 951 HIV-uninfected and 748 HIV
      infected subjects with TBM were included; 219 of 951 (23.0%) and 384 of 748
      (51.3%) died during 9-month follow-up. Common predictors for increased mortality
      in both populations were higher Medical Research Council (MRC) disease severity
      grade and lower cerebrospinal fluid lymphocyte cell count. In HIV-uninfected
      subjects, older age, previous tuberculosis, not receiving adjunctive
      dexamethasone, and focal neurological signs were additional risk factors; in HIV
      infected subjects, lower weight, lower peripheral blood CD4 cell count, and
      abnormal plasma sodium were additional risk factors. The areas under the receiver
      operating characteristic curves (AUCs) for the final prognostic models were 0.77
      (HIV-uninfected population) and 0.78 (HIV-infected population), demonstrating
      better discrimination than the MRC grade (AUC, 0.66 and 0.70) or Glasgow Coma
      Scale score (AUC, 0.68 and 0.71) alone. Conclusions: The developed models showed
      good performance and could be used in clinical practice to assist physicians in
      identifying patients with TBM at high risk of death and with increased need of
      supportive care.

PMID- 29029054
TI  - Prostaglandin-Endoperoxide Synthase 1 Mediates the Timing of Parturition in Mice
      Despite Unhindered Uterine Contractility.
AB  - Cyclooxygenase (COX)-derived prostaglandins stimulate uterine contractions and
      prepare the cervix for parturition. Prior reports suggest Cox-1 knockout (KO)
      mice exhibit delayed parturition due to impaired luteolysis, yet the mechanism
      for late-onset delivery remains unclear. Here, we examined key factors for normal
      onset of parturition to determine whether any could account for the delayed
      parturition phenotype. Pregnant Cox-1KO mice did not display altered timing of
      embryo implantation or postimplantation growth. Although messenger RNAs of
      contraction-associated proteins (CAPs) were differentially expressed between Cox
      1KO and wild-type (WT) myometrium, there were no differences in CAP agonist
      induced intracellular calcium release, spontaneous or oxytocin (OT)-induced ex
      vivo uterine contractility, or in vivo uterine contractile pressure. Delayed
      parturition in Cox-1KO mice persisted despite exogenous OT treatment.
      Progesterone (P4) withdrawal, by ovariectomy or administration of the P4
      antagonist RU486, diminished the delayed parturition phenotype of Cox-1KO mice.
      Because antepartum P4 levels do not decline in Cox-1KO females, P4-treated WT
      mice were examined for the effect of this hormone on in vivo uterine
      contractility and ex vivo cervical dilation. P4-treated WT mice had delayed
      parturition but normal uterine contractility. Cervical distensibility was
      decreased in Cox-1KO mice on the day of expected delivery and reduced in WT mice
      with long-term P4 treatment. Collectively, these findings show that delayed
      parturition in Cox-1KO mice is the result of impaired luteolysis and cervical
      dilation, despite the presence of strong uterine contractions.

PMID- 29029056
TI  - Time to Switch to Second-line Antiretroviral Therapy in Children With Human
      Immunodeficiency Virus in Europe and Thailand.
AB  - Background: Data on durability of first-line antiretroviral therapy (ART) in
      children with human immunodeficiency virus (HIV) are limited. We assessed time to
      switch to second-line therapy in 16 European countries and Thailand. Methods:
      Children aged <18 years initiating combination ART (>=2 nucleoside reverse
      transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase
      inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to
      second-line was defined as (i) change across drug class (PI to NNRTI or vice
      versa) or within PI class plus change of >=1 NRTI; (ii) change from single to
      dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch
      was calculated with death and loss to follow-up as competing risks. Results: Of
      3668 children included, median age at ART initiation was 6.1 (interquartile range
      (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP)
      based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9
      8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence
      interval, 20%-23%), with significant regional variations. Median time to switch
      was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment
      failure. In multivariable analysis, older age, severe immunosuppression and
      higher viral load (VL) at ART start, and NVP-based initial regimens were
      associated with increased risk of switch. Conclusions: One in 5 children switched
      to a second-line regimen by 5 years of ART, with two-thirds failure related.
      Advanced HIV, older age, and NVP-based regimens were associated with increased
      risk of switch.

PMID- 29029057
TI  - Patient-specific modelling of regional tobramycin concentration levels in airways
      of patients with cystic fibrosis: can we dose once daily?
AB  - Background: Inhaled tobramycin is important in the treatment of Pseudomonas
      aeruginosa (Pa) infections in cystic fibrosis (CF). However, despite its use it
      fails to attenuate the clinical progression of CF lung disease. The bactericidal
      efficacy of tobramycin is known to be concentration-dependent and hence changing
      the dosing regimen from a twice-daily (q12h) inhalation to a once-daily (q24h)
      inhaled double dose could improve treatment outcomes. Objectives: To predict
      local concentrations of nebulized tobramycin in the airways of patients with CF,
      delivered with the small airway-targeting Akita(r) system or standard PARI-LC(r)
      Plus system, with different inspiratory flow profiles. Methods: Computational
      fluid dynamic (CFD) methods were applied to patient-specific airway models
      reconstructed from chest CT scans. The following q12h and q24h dosing regimens
      were evaluated: Akita(r) (150 and 300 mg) and PARI-LC(r) Plus (300 and 600 mg).
      Site-specific concentrations were calculated. Results: Twelve CT scans from
      patients aged 12-17 years (median = 15.7) were selected. Small airway
      concentrations were 762-2999 mg/L for the q12h dosing regimen and 1523-5997 mg/L
      for the q24h dosing regimen, well above the MIC for WT Pa strains. Importantly,
      the q24h regimen appeared to be more suitable than the q12h regimen against more
      resistant Pa strains and the inhibitory effects of sputum on tobramycin activity.
      Conclusions: CFD modelling showed that high concentrations of inhaled tobramycin
      are indeed delivered to the airways, with the Akita(r) system being twice as
      efficient as the PARI-LC(r) system. Ultimately, the q24h dosing regimen appears
      more effective against subpopulations with high MICs (i.e. more resistant
      strains).

PMID- 29029058
TI  - Inter-ethnic differences in valve morphology, valvular dysfunction, and
      aortopathy between Asian and European patients with bicuspid aortic valve.
AB  - Background: Transcatheter aortic valve replacement (TAVR) has been shown safe and
      feasible in patients with bicuspid aortic valve (BAV) morphology. Evaluation of
      inter-ethnic differences in valve morphology and function and aortic root
      dimensions in patients with BAV is important for the worldwide spread of this
      therapy in this subgroup of patients. Comparisons between large European and
      Asian cohorts of patients with BAV have not been performed, and potential
      differences between populations may have important implications for TAVR. Aim:
      The present study evaluated the differences in valve morphology and function and
      aortic root dimensions between two large cohorts of European and Asian patients
      with BAV. Methods and results: Aortic valve morphology was defined on
      transthoracic echocardiography according to the number of commissures and raphe:
      type 0 = no raphe and two commissures, type 1 = one raphe and two commissures,
      type 2 = two raphes and one commissure. Aortic stenosis and regurgitation were
      graded according to current recommendations. For this study, aortic root
      dimensions were manually measured on transthoracic echocardiograms at the level
      of the aortic annulus, sinus of Valsalva (SOV), sinotubular junction (STJ), and
      ascending aorta (AA). Of 1427 patients with BAV (45.2 +/- 18.1 years, 71.9% men),
      794 (55.6%) were Europeans and 633 (44.4%) were Asians. The groups were
      comparable in age and proportion of male sex. Asians had higher prevalence of
      type 1 BAV with raphe between right and non-coronary cusps than Europeans (19.7%
      vs. 13.6%, respectively; P < 0.001), whereas the Europeans had higher prevalence
      of type 0 BAV (two commissures, no raphe) than Asians (14.5% vs. 6.8%,
      respectively; P < 0.001). The prevalence of moderate and severe aortic
      regurgitation was higher in Europeans than Asians (44.2% vs. 26.8%, respectively;
      P < 0.001) whereas there were no differences in BAV with normal function or
      aortic stenosis. After adjusting for demographics, comorbidities, and valve
      function, the dimensions of the aortic annulus [mean difference 1.17 mm/m2, 95%
      confidence interval (CI) 0.96-1.39], SOV (mean difference 1.86 mm/m2, 95% CI 1.47
      2.24), STJ (mean difference 0.52 mm/m2, 95% CI 0.14-0.90) and AA (mean difference
      1.05 mm/m2, 95% CI 0.57-1.52) were significantly larger among Asians compared
      with Europeans. Conclusions: This large multicentre registry reports for the
      first time that Asians with BAV showed more frequently type 1 BAV (with fusion
      between right and non-coronary cusp) and have larger aortic dimensions than
      Europeans. These findings have important implications for prosthesis type and
      size selection for TAVR.

PMID- 29029059
TI  - Canonical Wnt/beta-Catenin Signaling Regulates Postnatal Mouse Epididymal
      Development But Does Not Affect Epithelial Cell Differentiation.
AB  - The epithelial lining of the epididymis establishes an optimal environment in
      which spermatozoa acquire the ability to fertilize an oocyte. This highly
      specialized organ develops from a simple embryonic tube known as the Wolffian
      duct (WD). How the simple columnar epithelium of WD acquires the complex features
      of the adult epididymal epithelium is currently unclear. During these first few
      weeks after birth, the epididymal epithelium undergoes major changes and by 5
      weeks consists of four different cell types. The main objective of this study was
      to evaluate potential roles of Wnt signaling during postnatal epididymal
      development and differentiation. To analyze the activity of Wnt signaling during
      postnatal development, we evaluated the epididymis of TCFGFP mice, a Wnt reporter
      mouse model. Wnt signaling activity as indicated by green fluorescent protein
      expression was detected in the whole epididymis of TCFGFP mice during the first 2
      weeks of life but was localized only to the caput region by 5 weeks of age. Using
      a genetic cell lineage tracing approach, we showed that all four of the
      epididymal epithelial cell types originated from the simple columnar epithelium
      of WD. To delineate the functional significance of epithelial Wnt signaling in
      epididymal development and differentiation, we generated a mouse model in which
      beta-catenin (Ctnnb1) was specifically ablated from the epididymal epithelium
      upon administration of doxycycline. Genetic suppression of epithelial Wnt/beta
      catenin signaling inhibited epididymal development by affecting cell
      proliferation but had no effect on epithelial cell differentiation.

PMID- 29029060
TI  - Metagenomics: novel enzymes from non-culturable microbes.
AB  - In the transition to the post-petroleum economy, there is a growing demand for
      novel enzymes with high process performances to replace traditional chemistry
      with a more 'green' approach. To date, microorganisms encompass the richest
      source of industrial biocatalysts, but the Earth-living microbiota remains
      largely untapped by using traditional isolation and cultivation methods.
      Metagenomics, which is culture independent, represents a powerful tool for
      discovering novel enzymes from unculturable microorganisms. Herein, we summarize
      the variety of approaches adopted for mining environmental DNA and, based on a
      systematic literature review, we provide a comprehensive list of 332 industrially
      relevant enzymes discovered from metagenomes within the last three years.

PMID- 29029061
TI  - Effects of access to radiology in out-of-hours primary care in the Netherlands: a
      prospective observational study.
AB  - Background: In the Netherlands, out-of-hours primary care is provided in general
      practitioner-cooperatives (GPCs). These are increasingly located on site with
      emergency departments (ED), forming Emergency-Care-Access-Points (ECAP). A more
      efficient and economical organization of out-of-hours primary emergency care
      could be realized by increased collaboration at an ECAP. In this study, we
      compared the effects of different models with respect to access to (hospital)
      radiology by the GPC. We investigated patient and care characteristics,
      indication for diagnostics and outcomes at GPCs with and without access to
      radiology. Methods: A prospective observational record review study of patients
      referred for conventional radiology for trauma by one of five GPCs in the period
      April 2014-October 2015, covering three organizational models. Results: The mean
      age was 31 years and 56% was female. Extremities were predominately involved
      (91%). There was a medical indication for radiology in 85% and the assessed risk
      by requesting GPs on abnormalities was high in 66%. There was a significant
      difference in outcomes between models. Radiological abnormalities
      (fractures/luxations) were present in 51% without direct access and in 35% with
      partial and unlimited access. Overall, 61% of the included patients were referred
      to the ED; 100% in the models without access and 38% in the models with (partial)
      access. Conclusions: GPC access to radiology is beneficial for patients and
      professionals. The diagnostics were adequately used. With access to radiology,
      unnecessary referrals and specialist care are prevented. This may lead to a
      decrease in ED attendance and overcrowding.

PMID- 29029062
TI  - Multicentric evaluation of the impact of central tumour location when comparing
      rates of N1 upstaging in patients undergoing video-assisted and open surgery for
      clinical Stage I non-small-cell lung cancer.
AB  - OBJECTIVES: Large retrospective series have indicated lower rates of cN0 to pN1
      nodal upstaging after video-assisted thoracic surgery (VATS) compared with open
      resections for Stage I non-small-cell lung cancer (NSCLC). The objective of our
      multicentre study was to investigate whether the presumed lower rate of N1
      upstaging after VATS disappears after correction for central tumour location in a
      multivariable analysis. METHODS: Consecutive patients operated for PET-CT based
      clinical Stage I NSCLC were selected from prospectively managed surgical
      databases in 11 European centres. Central tumour location was defined as contact
      with bronchovascular structures on computer tomography and/or visibility on
      standard bronchoscopy. RESULTS: Eight hundred and ninety-five patients underwent
      pulmonary resection by VATS (n = 699, 9% conversions) or an open technique (n =
      196) in 2014. Incidence of nodal pN1 and pN2 upstaging was 8% and 7% after VATS
      and 15% and 6% after open surgery, respectively. pN1 was found in 27% of patients
      with central tumours. Less central tumours were operated on by VATS compared with
      the open technique (12% vs 28%, P < 0.001). Logistic regression analysis showed
      that only tumour location had a significant impact on N1 upstaging (OR 6.2,
      confidence interval 3.6-10.8; P < 0.001) and that the effect of surgical
      technique (VATS versus open surgery) was no longer significant when accounting
      for tumour location. CONCLUSIONS: A quarter of patients with central clinical
      Stage I NSCLC was upstaged to pN1 at resection. Central tumour location was the
      only independent factor associated with N1 upstaging, undermining the evidence
      for lower N1 upstaging after VATS resections. Studies investigating N1 upstaging
      after VATS compared with open surgery should be interpreted with caution due to
      possible selection bias, i.e. relatively more central tumours in the open group
      with a higher chance of N1 upstaging.

PMID- 29029063
TI  - Impact of Pneumococcal Vaccination on Pneumonia Hospitalizations and Related
      Costs in Ontario: A Population-Based Ecological Study.
AB  - Background: In Ontario, Canada, pneumococcal conjugate vaccine (PCV) was approved
      for infants in 2001 and became part of the publicly funded routine immunization
      schedule in 2005. We assessed the population-level impact of PCV on pneumonia
      hospitalizations and related costs. Methods: We used the difference-in
      differences approach to evaluate the impact of pneumococcal vaccination on
      pneumonia hospitalizations and related costs, using nonpneumonia hospitalization
      as the control condition. We extracted monthly hospitalization costs, stratified
      by age group, from population-based health administrative data between April 1992
      and March 2014. The study period was divided into 5 intervals: prevaccine period,
      availability of 7-valent PCV (PCV7) for private purchase, public funding for
      PCV7, replacement of PCV7 with 10-valent PCV (PCV10), and replacement of PCV10
      with 13-valent PCV (PCV13). Results: A total of 1063700 pneumonia
      hospitalizations were recorded during the study period. In the vaccine-eligible
      age group, pneumonia hospitalizations declined by 34% (95% confidence interval,
      32%-37%), 38% (32%-43%), and 45% (40%-51%) and hospitalization-related costs
      declined by 38% (25%-51%), 39% (33%-45%), and 46% (41%-52%) after public funding
      for PCV7, PCV10, and PCV13, respectively. Pneumonia hospitalizations and related
      costs also declined substantially for PCV-ineligible older children and elderly
      persons (aged >65 years). Conclusions: Our results suggest that the publicly
      funded PCV immunization program is responsible for substantial reductions in
      pneumonia hospitalizations and related healthcare costs, among both young
      children eligible for publicly funded vaccination and other age groups not
      included in the publicly funded program.

PMID- 29029065
TI  - Emergence of Escherichia coli co-producing NDM-1 and KPC-2 carbapenemases from a
      retail vegetable, China.

PMID- 29029064
TI  - 2015-2016 Vaccine Effectiveness of Live Attenuated and Inactivated Influenza
      Vaccines in Children in the United States.
AB  - Background: In the 2015-2016 season, quadrivalent live attenuated influenza
      vaccine (LAIV) and both trivalent and quadrivalent inactivated influenza vaccine
      (IIV) were available in the United States. Methods: This study, conducted
      according to a test-negative case-control design, enrolled children aged 2-17
      years presenting to outpatient settings with fever and respiratory symptoms for
      <5 days at 8 sites across the United States between 30 November 2015 and 15 April
      2016. A nasal swab was obtained for reverse-transcriptase polymerase chain
      reaction (RT-PCR) testing for influenza, and influenza vaccination was verified
      in the medical record or vaccine registry. Influenza vaccine effectiveness (VE)
      was estimated using a logistic regression model. Results: Of 1012 children
      retained for analysis, most children (59%) were unvaccinated, 10% received LAIV,
      and 31% received IIV. Influenza A (predominantly antigenically similar to the
      A/California/7/2009 strain) was detected in 14% and influenza B (predominantly a
      B/Victoria lineage) in 10%. For all influenza, VE was 46% (95% confidence
      interval [CI], 7%-69%) for LAIV and 65% (48%-76%) for IIV. VE against influenza
      A(H1N1)pdm09 was 50% (95% CI, -2% to 75%) for LAIV and 71% (51%-82%) for IIV. The
      odds ratio for vaccine failure with RT-PCR-confirmed A(H1N1)pdm09 was 1.71 (95%
      CI, 0.78-3.73) in LAIV versus IIV recipients. Conclusions: LAIV and IIV
      demonstrated effectiveness against any influenza among children aged 2-17 years
      in 2015-2016. When compared to all unvaccinated children, VE against influenza
      A(H1N1)pdm09 was significant for IIV but not LAIV. Clinical Trials Registration:
      NCT01997450.

PMID- 29029066
TI  - National disparities in the relationship between antimicrobial resistance and
      antimicrobial consumption in Europe: an observational study in 29 countries
      authors' response.

PMID- 29029067
TI  - Pharmacodynamics of fosfomycin against ESBL- and/or carbapenemase-producing
      Enterobacteriaceae.
AB  - Background: The increase in antibiotic resistance in Gram-negative bacteria and
      the limited therapeutic options due to the shortage of new antibiotics have
      increased the interest of the 'old' antibiotic fosfomycin in the treatment of
      infections. However, there are contradictory reports on the pharmacodynamics of
      and emergence of resistance to fosfomycin. Methods: Time-kill assays were
      performed with 11 ESBL-positive and 3 ESBL-negative strains, exposing the
      bacteria to 2-fold static concentrations from 0.125* to 32* MIC. The sigmoid
      maximum effect (Emax) model was fitted to the time-kill curve data. Amplification
      of resistance over time was evaluated under various conditions of selective
      pressure by plating on 16* MIC plates. Results: Fosfomycin was bactericidal for
      all strains within 8 h. Using the Emax model, no significant differences between
      strains were observed for the pharmacodynamic parameters. However, the large
      variation in Hill slope factors for Escherichia coli of 0.87 up to 4.02 indicates
      that the killing behaviour appears to be more time dependent for some strains but
      concentration dependent for others. In the fosfomycin-exposed cultures under low
      and high selective pressure (>=2* MIC) the median resistance proportions between
      the resistant and total population increased from <=2 * 10-6 (T = 0 h) to 0.652
      0.899 (T = 24 h). Resistance appeared stable after repeated subculturing.
      Conclusions: Killing behaviour of fosfomycin does not only differ between species
      but also within species and may have an impact on the design of optimal dosing
      regimens. Although fosfomycin was bactericidal against all strains (re)growth of
      resistant subpopulations occurred relatively fast. This may limit the use of
      fosfomycin as a single drug therapy.

PMID- 29029069
TI  - Molting Site Fidelity in Workers of Formosan Subterranean Termites (Isoptera:
      Rhinotermitidae).
AB  - Spatial assessment of molting in workers of Coptotermes formosanus Shiraki was
      conducted in laboratory-reared colonies using extended foraging arenas. Workers
      at a premolt stage were found concentrated in the nest or in a planar arena near
      the nest. However, molting individuals were found exclusively in the central nest
      and they stayed inside or near the central nest for at least 36 h postmolting.
      The absence of premolt workers at foraging sites suggests that the workers have
      an affinity to the nest for molting and the second study on nest-fidelity
      evaluation suggested that the workers molt in the proximity of eggs. The molting
      site fidelity by workers in a colony ensures that speeding up the time for
      mortality induced by chitin synthesis inhibitor (CSI) baits will not result in an
      inhibitory cascade of dead termites around the bait stations. Thus, speeding up
      the elimination of a C. formosanus colony using CSI baits with the addition of
      molt-accelerating compounds will not lead to secondary repellency. Reasons for
      the molting-site fidelity amongst workers in a colony are discussed.

PMID- 29029068
TI  - Considering health equity when moving from evidence-based guideline
      recommendations to implementation: a case study from an upper-middle income
      country on the GRADE approach.
AB  - The availability of evidence-based guidelines does not ensure their
      implementation and use in clinical practice or policy making. Inequities in
      health have been defined as those inequalities within or between populations that
      are avoidable, unnecessary and also unjust and unfair. Evidence-based clinical
      practice and public health guidelines ('guidelines') can be used to target health
      inequities experienced by disadvantaged populations, although guidelines may
      unintentionally increase health inequities. For this reason, there is a need for
      evidence-based clinical practice and public health guidelines to intentionally
      target health inequities experienced by disadvantaged populations. Current
      guideline development processes do not include steps for planned implementation
      of equity-focused guidelines. This article describes nine steps that provide
      guidance for consideration of equity during guideline implementation. A critical
      appraisal of the literature followed by a process to build expert consensus was
      undertaken to define how to include consideration of equity issues during the
      specific GRADE guideline development process. Using a case study from Colombia we
      describe nine steps that were used to implement equity-focused GRADE
      recommendations: (1) identification of disadvantaged groups, (2) quantification
      of current health inequities, (3) development of equity-sensitive
      recommendations, (4) identification of key actors for implementation of equity
      focused recommendations, (5) identification of barriers and facilitators to the
      implementation of equity-focused recommendations, (6) development of an equity
      strategy to be included in the implementation plan, (7) assessment of resources
      and incentives, (8) development of a communication strategy to support an equity
      focus and (9) development of monitoring and evaluation strategies. This case
      study can be used as model for implementing clinical practice guidelines, taking
      into account equity issues during guideline development and implementation.

PMID- 29029070
TI  - Development and validation of an LC tandem MS assay for the quantification of
      beta-lactam antibiotics in the sputum of cystic fibrosis patients.
AB  - Objectives: Antibiotic therapy is of vital importance for the control of
      infectious exacerbations in cystic fibrosis (CF) patients. However, very little
      is known regarding the fraction of systemically administered antibiotics reaching
      the lower respiratory tract secretions. We developed and validated a method to
      measure the concentrations of piperacillin, ceftazidime, meropenem and aztreonam
      in CF sputum, and present the validation data. Methods: Ultra-performance LC
      coupled to tandem MS was used. A single sample can be measured in 2.5 min with
      multiple reaction monitoring in positive electrospray ionization mode. Deuterated
      internal standards were used and a concentration range of 0.7-160 mg/L was
      covered. The method was validated according to the EMA guideline on analytical
      method validation. Results: The boundaries within which a reliable measurement in
      CF sputum can be performed were determined. A few constraints are linked to the
      instability of the antibiotics in sputum. Piperacillin showed limited stability
      at room temperature and during freeze-thaw cycles. Autosampler instability was
      observed after 15 h for aztreonam at low concentrations. Conclusions: The method
      allows a reliable measurement of the selected antibiotics, if precautions are
      taken regarding the limited stability of piperacillin at room temperature. Due to
      freeze-thaw instability, piperacillin should always be analysed on the day of
      sampling. Quick review of the analytical data and reanalysis are needed as low
      concentrations of aztreonam are not stable in the autosampler.

PMID- 29029071
TI  - Visual Cortex Limits Pop-Out in the Superior Colliculus of Awake Mice.
AB  - We detect objects more readily if they differ from their surroundings in motion,
      color, or texture. This increased saliency is thought to be related to increased
      responses in the visual cortex. The superior colliculus is another brain area
      involved in vision and especially in directing gaze and attention. In this study,
      we show that differences in texture orientation also increase responses in the
      superficial layers of the superior colliculus that receive retinal and cortical
      input. We found that gratings evoke more neural response when surrounded by
      orthogonal gratings than when surrounded by parallel gratings, particularly in
      the awake mouse. This pop-out is not originating from the visual cortex, and
      silencing visual cortex increased the relative difference in response. A model
      shows that this can result from retinotopically matched excitation from visual
      cortex to the superior colliculus. We suggest that the perceptual saliency of a
      stimulus differing from its surround in a low-level feature like grating
      orientation could depend on visual processing in the superior colliculus.

PMID- 29029072
TI  - Detection of optrA in the African continent (Tunisia) within a mosaic
      Enterococcus faecalis plasmid from urban wastewaters.
AB  - Objectives: Oxazolidinone resistance is a serious limitation in the treatment of
      MDR Enterococcus infections. Plasmid-mediated oxazolidinone resistance has been
      strongly linked to animals where the use of phenicols might co-select resistance
      to both antibiotic families. Our goal was to assess the diversity of genes
      conferring phenicol/oxazolidinone resistance among diverse enterococci and to
      characterize the optrA genetic environment. Methods: Chloramphenicol-resistant
      isolates (>16 mg/L, n = 245) from different sources (hospitals/healthy
      humans/wastewaters/animals) in Portugal, Angola and Tunisia (1996-2016) were
      selected. Phenicol (eight cat variants, fexA, fexB) or phenicol + oxazolidinone
      [cfr, cfr(B), optrA] resistance genes were searched for by PCR. Susceptibility
      (disc diffusion/microdilution), filter mating, stability of antibiotic resistance
      (500 bacterial generations), plasmid typing (S1-PFGE/hybridization), MLST and WGS
      (Illumina-HiSeq) were performed for optrA-positive isolates. Results: Resistance
      to phenicols (n = 181, 74%) and phenicols + oxazolidinones (n = 2, 1%) was
      associated with the presence of cat(A-8) (40%, predominant in hospitals and
      swine), cat(A-7) (29%, predominant in poultry and healthy humans), cat(A-9) (2%),
      fexB (2%) and fexA + optrA (1%). fexA and optrA genes were co-located in a
      transferable plasmid (pAF379, 72 918 bp) of two ST86 MDR Tunisian Enterococcus
      faecalis (wastewaters) carrying several putative virulence genes. MICs of
      chloramphenicol, linezolid and tedizolid were stably maintained at 64, 4 and 1
      mg/L, respectively. The chimeric pAF379 comprised relics of genetic elements from
      different Gram-positive bacteria and origins (human/porcine). Conclusions: To the
      best of our knowledge, we report the first detection of optrA in an African
      country (Tunisia) within a transferable mosaic plasmid of different origins. Its
      identification in isolates from environmental sources is worrisome and alerts for
      the need of a concerted global surveillance on the occurrence and spread of
      optrA.

PMID- 29029074
TI  - Multimodality imaging evaluation of Chagas disease: an expert consensus of
      Brazilian Cardiovascular Imaging Department (DIC) and the European Association of
      Cardiovascular Imaging (EACVI).
AB  - Aims: To develop a document by Brazilian Cardiovascular Imaging Department (DIC)
      and the European Association of Cardiovascular Imaging (EACVI) to review and
      summarize the most recent evidences about the non-invasive assessment of patients
      with Chagas disease, with the intent to set up a framework for standardized
      cardiovascular imaging to assess cardiovascular morphologic and functional
      disturbances, as well as to guide the subsequent process of clinical decision
      making. Methods and results: Chagas disease remains one of the most prevalent
      infectious diseases in Latin America, and has become a health problem in non
      endemic countries. Dilated cardiomyopathy is the most severe manifestation of
      Chagas disease, which causes substantial disability and early mortality in the
      socially most productive population leading to a significant economical burden.
      Prompt and correct diagnosis of Chagas disease requires specialized clinical
      expertise to recognize the unique features of this disease. The appropriate and
      efficient use of cardiac imaging is pivotal for diagnosing the cardiac
      involvement in Chagas disease, to stage the disease, assess patients' prognosis
      and address management. Echocardiography is the most common imaging modality used
      to assess, and follow-up patients with Chagas disease. The presence of
      echocardiographic abnormalities is of utmost importance, since it allows to stage
      patients according to disease progression. In early stages of cardiac
      involvement, echocardiography may demonstrate segmental left ventricuar wall
      motion abnormalities, mainly in the basal segments of inferior, inferolateral
      walls, and the apex, which cannot be attributed to obstructive coronary artery
      arteries. The prevalence of segmental wall motion abnormalities varies according
      to the stage of the disease, reaching about 50% in patients with left ventricular
      dilatation and dysfunction. Speckle tracking echocardiography allows a more
      precise and quantitative measurement of the regional myocardial function. Since
      segmental wall motion abnormalities are frequent in Chagas disease, speckle
      tracking echocardiography may have an important clinical application in these
      patients, particularly in the indeterminate forms when abnormalities are more
      subtle. Speckle tracking echocardiography can also quantify the heterogeneity of
      systolic contraction, which is associated with the risk of arrhythmic events.
      Three-dimensional (3D) echocardiography is superior to conventional two
      dimensional (2D) echocardiography for assessing more accurately the left
      ventricular apex and thus to detect apical aneurysms and thrombus in patients in
      whom ventricular foreshortening is suspected by 2D echocardiography. In addition,
      3D echocardiography is more accurate than 2D Simpson s biplane rule for assessing
      left ventricular volumes and function in patients with significant wall motion
      abnormalities, including aneurysms with distorted ventricular geometry. Contrast
      echocardiography has the advantage to enhancement of left ventricular endocardial
      border, allowing for more accurate detection of ventricular aneurysms and
      thrombus in Chagas disease. Diastolic dysfunction is an important hallmark of
      Chagas disease even in its early phases. In general, left ventricular diastolic
      and systolic dysfunction coexist and isolated diastolic dysfunction is uncommon
      but may be present in patients with the indeterminate form. Right ventricular
      dysfunction may be detected early in the disease course, but in general, the
      clinical manifestations occur late at advanced stages of Chagas cardiomyopathy.
      Several echocardiographic parameters have been used to assess right ventricular
      function in Chagas disease, including qualitative evaluation, myocardial
      performance index, tissue Doppler imaging, tricuspid annular plane systolic
      excursion, and speckle tracking strain. Cardiac magnetic resonance (CMR) is
      useful to assess global and regional left ventricular function in patients with
      Chagas diseases. Myocardial fibrosis is a striking feature of Chagas
      cardiomyopathy and late gadolinium enhancement (LGE) is used to detect and
      quantify the extension of myocardial fibrosis. Myocardial fibrosis might have a
      role in risk stratification of patients with Chagas disease. Limited data are
      available regarding right ventricular function assessed by CMR in Chagas disease.
      Radionuclide ventriculography is used for global biventricular function
      assessment in patients with suspected or definite cardiac involvement in Chagas
      disease with suboptimal acoustic window and contraindication to CMR. Myocardial
      perfusion scintigraphy may improve risk stratification to define cardiac
      involvement in Chagas disease, especially in the patients with devices who cannot
      be submitted to CMR and in the clinical setting of Chagas patients whose main
      complaint is atypical chest pain. Detection of reversible ischemic defects
      predicts further deterioration of left ventricular systolic function and helps to
      avoid unnecessary cardiac catheterization and coronary angiography. Conclusion:
      Cardiac imaging is crucial to detect the cardiac involvement in patients with
      Chagas disease, stage the disease and stratify patient risk and address
      management. Unfortunately, most patients live in regions with limited access to
      imaging methods and point-of-care, simplified protocols, could improve the access
      of these remote populations to important information that could impact in the
      clinical management of the disease. Therefore, there are many fields for further
      research in cardiac imaging in Chagas disease. How to better provide an earlier
      diagnosis of cardiac involvement and improve patients risk stratification remains
      to be addressed using different images modalities.

PMID- 29029073
TI  - Clinical genetics and outcome of left ventricular non-compaction cardiomyopathy.
AB  - Aims: In this study, we aimed to clinically and genetically characterize LVNC
      patients and investigate the prevalence of variants in known and novel LVNC
      disease genes. Introduction: Left ventricular non-compaction cardiomyopathy
      (LVNC) is an increasingly recognized cause of heart failure, arrhythmia,
      thromboembolism, and sudden cardiac death. We sought here to dissect its genetic
      causes, phenotypic presentation and outcome. Methods and results: In our registry
      with follow-up of in the median 61 months, we analysed 95 LVNC patients (68
      unrelated index patients and 27 affected relatives; definite familial LVNC =
      23.5%) by cardiac phenotyping, molecular biomarkers and exome sequencing.
      Cardiovascular events were significantly more frequent in LVNC patients compared
      with an age-matched group of patients with non-ischaemic dilated cardiomyopathy
      (hazard ratio = 2.481, P = 0.002). Stringent genetic classification according to
      ACMG guidelines revealed that TTN, LMNA, and MYBPC3 are the most prevalent
      disease genes (13 patients are carrying a pathogenic truncating TTN variant, odds
      ratio = 40.7, Confidence interval = 21.6-76.6, P < 0.0001, percent spliced in 76
      100%). We also identified novel candidate genes for LVNC. For RBM20, we were able
      to perform detailed familial, molecular and functional studies. We show that the
      novel variant p.R634L in the RS domain of RBM20 co-segregates with LVNC, leading
      to titin mis-splicing as revealed by RNA sequencing of heart tissue in mutation
      carriers, protein analysis, and functional splice-reporter assays. Conclusion:
      Our data demonstrate that the clinical course of symptomatic LVNC can be severe.
      The identified pathogenic variants and distribution of disease genes-a titin
      related pathomechanism is found in every fourth patient-should be considered in
      genetic counselling of patients. Pathogenic variants in the nuclear proteins
      Lamin A/C and RBM20 were associated with worse outcome.

PMID- 29029075
TI  - Improving health systems performance in low- and middle-income countries: a
      system dynamics model of the pay-for-performance initiative in Afghanistan.
AB  - System dynamics methods were used to explore effective implementation pathways
      for improving health systems performance through pay-for-performance (P4P)
      schemes. A causal loop diagram was developed to delineate primary causal
      relationships for service delivery within primary health facilities. A
      quantitative stock-and-flow model was developed next. The stock-and-flow model
      was then used to simulate the impact of various P4P implementation scenarios on
      quality and volume of services. Data from the Afghanistan national facility
      survey in 2012 was used to calibrate the model. The models show that P4P bonuses
      could increase health workers' motivation leading to higher levels of quality and
      volume of services. Gaming could reduce or even reverse this desired effect,
      leading to levels of quality and volume of services that are below baseline
      levels. Implementation issues, such as delays in the disbursement of P4P bonuses
      and low levels of P4P bonuses, also reduce the desired effect of P4P on quality
      and volume, but they do not cause the outputs to fall below baseline levels.
      Optimal effect of P4P on quality and volume of services is obtained when P4P
      bonuses are distributed per the health workers' contributions to the services
      that triggered the payments. Other distribution algorithms such as equal
      allocation or allocations proportionate to salaries resulted in quality and
      volume levels that were substantially lower, sometimes below baseline. The system
      dynamics models served to inform, with quantitative results, the theory of change
      underlying P4P intervention. Specific implementation strategies, such as prompt
      disbursement of adequate levels of performance bonus distributed per health
      workers' contribution to service, increase the likelihood of P4P success. Poorly
      designed P4P schemes, such as those without an optimal algorithm for distributing
      performance bonuses and adequate safeguards for gaming, can have a negative
      overall impact on health service delivery systems.

PMID- 29029076
TI  - Neoliberal Long-Term Care: From Community to Corporate Control.
AB  - Publicly (mainly Medicaid) funded long-term care (LTC) services have evolved from
      a nursing home dominated system of service to a much more balanced system
      including home- and community-based services (HCBS) programs over the last 30
      years. The HCBS programs have been largely administered by the state and local
      level nonprofit aging networks (ANs) consisting of Area Agencies on Aging and
      thousands of service providers. Over the last decade, however, for-profit HMOs
      administered primarily by large insurance companies have begun to displace AN
      organizations. State policymakers have embraced for-profit privatizations under
      the rationale that this approach will generate greater savings, efficiencies, and
      higher quality outcomes than the traditional public or private nonprofit models
      of program administration. As we show here, there is very little evidence for
      this rationale; yet, this lack of evidence has not prevented the continuing
      growth of for-profit managed LTC programs supported more by an ideology of market
      fundamentalism than empirical evidence. We also describe six possible
      consequences of the trend toward corporate control of public LTC services in the
      years ahead.

PMID- 29029077
TI  - Association of Obesity, Diabetes, and Risk of Tuberculosis: Two Population-Based
      Cohorts.
AB  - Background: Mounting data have revealed that body mass index (BMI) is inversely
      associated with risk of active tuberculosis. The inverse association presents a
      "paradox" with regard to diabetes, because obesity is a major determinant of
      diabetes, and diabetes is a well-known risk factor for tuberculosis. Methods: We
      conducted 2 population-based cohort studies involving 167392 participants. The
      main exposure was BMI and diabetes ascertained at baseline. Occurrence of
      incident tuberculosis was ascertained from Taiwan's National Tuberculosis
      Registry. We conducted a causal mediation analysis and a joint effects analysis
      to characterize the relationship between BMI, diabetes, and tuberculosis.
      Results: During a median of >7 years of follow-up, 491 individuals developed
      incident tuberculosis. Compared with normal-weight individuals, obese individuals
      (>30 kg/m2) had a 67% (95% confidence interval [CI], -3% to -90%) and 64% (31%
      81%) reduction in tuberculosis hazard in the 2 cohorts. In the causal mediation
      analysis, obesity had a harmful effect on tuberculosis mediated through diabetes
      (0.8% and 2.7% increased odds in the 2 cohorts, respectively) but had a strongly
      protective effect not mediated through diabetes (72% and 67% decreased odds,
      respectively). Individuals who were simultaneously obese and diabetic had a lower
      but statistically insignificant risk of tuberculosis (adjusted hazard ratio,
      0.30; 95% CI, .08-1.22) compared with nondiabetic normal-weight individuals.
      Conclusions: Our analyses revealed that the relationship between obesity,
      diabetes, and risk of tuberculosis was complex and nonlinear. Better
      understanding of the interplay between host metabolism and tuberculosis
      immunology may lead to novel therapeutic or preventive strategies.

PMID- 29029078
TI  - Prebiotic potential of pectin and pectic oligosaccharides to promote anti
      inflammatory commensal bacteria in the human colon.
AB  - Dietary plant cell wall carbohydrates are important in modulating the composition
      and metabolism of the complex gut microbiota, which can impact on health. Pectin
      is a major component of plant cell walls. Based on studies in model systems and
      available bacterial isolates and genomes, the capacity to utilise pectins for
      growth is widespread among colonic Bacteroidetes but relatively uncommon among
      Firmicutes. One Firmicutes species promoted by pectin is Eubacterium eligens.
      Eubacterium eligens DSM3376 utilises apple pectin and encodes a broad repertoire
      of pectinolytic enzymes, including a highly abundant pectate lyase of around 200
      kDa that is expressed constitutively. We confirmed that certain Faecalibacterium
      prausnitzii strains possess some ability to utilise apple pectin and report here
      that F. prausnitzii strains in common with E. eligens can utilise the
      galacturonide oligosaccharides DP4 and DP5 derived from sugar beet pectin.
      Faecalibacterium prausnitzii strains have been shown previously to exert anti
      inflammatory effects on host cells, but we show here for the first time that E.
      eligens strongly promotes the production of the anti-inflammatory cytokine IL-10
      in in vitro cell-based assays. These findings suggest the potential to explore
      further the prebiotic potential of pectin and its derivatives to re-balance the
      microbiota towards an anti-inflammatory profile.

PMID- 29029079
TI  - Sialylation of extracellular superoxide dismutase (EC-SOD) enhances furin
      mediated cleavage and secretion.
AB  - Extracellular superoxide dismutase (EC-SOD, SOD3) protects tissues against
      oxidative damage by detoxifying superoxide anions, particularly in the lungs and
      cardiovascular system. EC-SOD undergoes several posttranslational modifications
      including N-glycosylation and proteolytic cleavage. While the roles of
      proteolytic cleavage have been well studied, the structure and function of EC-SOD
      N-glycans are poorly understood. Here we analyzed glycan structures on native EC
      SOD purified from human sera, and identified sialylated biantennary structures.
      Using glycan maturation-defective CHO mutant cells, we further revealed that the
      presence of terminal sialic acids in the N-glycans of EC-SOD enhanced both the
      secretion and furin-mediated C-terminal cleavage of EC-SOD. These results provide
      new insights into how the posttranslational modifications of EC-SOD control its
      functions.

PMID- 29029080
TI  - Recurrent purulent pericarditis secondary to a giant bronchogenic cyst.

PMID- 29029081
TI  - Rapid Cold-Hardening of a Subtropical Species, Maruca vitrata (Lepidoptera:
      Crambidae), Accompanies Hypertrehalosemia by Upregulating Trehalose-6-Phosphate
      Synthase.
AB  - A subtropical insect, Maruca vitrata (F.) (Lepidoptera: Crambidae), is invasive
      to temperate zones, in which low temperatures during winter would be a serious
      challenge for colonization. This study assessed cold tolerance and cold-hardening
      of M. vitrata to understand its overwintering mechanism. Supercooling capacity
      was confirmed in all developmental stages exhibiting body freezing points at
      lower than -10 degrees C, in which supercooling points (SCPs) were significantly
      different among developmental stages, with eggs having the lowest SCP (at -22.5
      degrees C). However, all developmental stages suffered significant mortality
      after being exposed to low temperatures much higher than SCPs. Furthermore,
      nonfreezing injury increased with elapsed time at 25 degrees C after cold shock.
      One of the nonfreezing symptoms was a darkening on thorax, which was explained by
      uncontrolled prophenoloxidase activation. Pre-exposure to 8 degrees C for 1 h
      significantly increased the survival of both young and old larvae to a low
      temperature treatment (-5 degrees C for 1 h). Rapid cold-hardening (RCH) was
      accompanied by significant increase in hemolymph trehalose concentration. During
      RCH, trehalose-6-phosphate synthase was significantly upregulated in its
      expression level. These results suggest that M. vitrata is a freeze-susceptible
      species and becomes cold-hardy via hypertrehalosemia.

PMID- 29029082
TI  - Decreased Homocysteine Trans-Sulfuration in Hypertension With
      Hyperhomocysteinemia: Relationship With Insulin Resistance.
AB  - Context: Homocysteine is an independent cardiovascular risk factor and is
      elevated in essential hypertension. Insulin stimulates homocysteine catabolism in
      healthy individuals. However, the mechanisms of hyperhomocysteinemia and its
      relationship with insulin resistance in essential hypertension are unknown.
      Objective: To investigate whole body methionine and homocysteine kinetics and the
      effects of insulin in essential hypertension. Design and Setting: Eight
      hypertensive male subjects and six male normotensive controls were infused with l
      [methyl-2H3,1-13C]methionine for 6 hours. In the last 3 hours a euglycemic,
      hyperinsulinemic clamp was performed. Steady-state methionine and homocysteine
      kinetics were determined in postabsorptive and hyperinsulinemic conditions.
      Results: Postabsorptive hypertensive subjects had elevated homocysteine
      concentrations (+30%, P = 0.035) and slightly (by 15% to 20%) but insignificantly
      lower methionine rates of appearance (Ras) (P = 0.07 to P = 0.05) and utilization
      for protein synthesis (P = 0.06) than postabsorptive normotensive controls.
      Hyperinsulinemia suppressed methionine Ra and protein synthesis, whereas it
      increased homocysteine trans-sulfuration, clearance, and methionine
      transmethylation (the latter only in the normotensive subjects). However, in the
      hypertensive subjects trans-sulfuration was significantly lower (P < 0.05) and
      increased ~50% less [by +1.59 +/- 0.34 vs +3.45 +/- 0.52 umol/kg lean body mass
      (LBM) per hour, P < 0.005] than in normotensive controls. Homocysteine clearance
      through trans-sulfuration was ~50% lower in hypertensive than in normotensive
      subjects (P < 0.005). In the hypertensive subjects, insulin-mediated glucose
      disposal was ~45% lower (460 +/- 44 vs 792 +/- 67 mg/kg LBM per hour, P < 0.0005)
      than in normotensive controls and was positively correlated with the increase of
      trans-sulfuration (P < 0.0015). Conclusions: In subjects with essential
      hypertension, hyperhomocysteinemia is associated with decreased homocysteine
      trans-sulfuration and probably represents a feature of insulin resistance.

PMID- 29029083
TI  - Unravelling the genome of a Pseudomonas aeruginosa isolate belonging to the high
      risk clone ST235 reveals an integrative conjugative element housing a blaGES-6
      carbapenemase.
AB  - Objectives: In Pseudomonas aeruginosa, the blaGES-6 carbapenemase gene was
      previously associated with an In1076 class I integron. Here, we conducted a
      genome-based analysis and explored the genetic platform associated with the
      mobility of this gene. Methods: WGS of a blaGES-6-harbouring P. aeruginosa
      isolate (FFUP_PS_690) was performed with Illumina HiSeq, de novo assembly was
      performed using SPAdes and subsequent bioinformatic analysis was performed
      concerning antibiotic resistance genes, virulence features and mobile genetic
      elements. Results: The FFUP_PS_690 isolate belongs to the ST235 high-risk clone
      and houses a novel integrative conjugative element (ICE), hereby named ICEPae690.
      This clc-like ICE comprises the blaGES-6-harbouring In1076 integron and specific
      modules. An ExoU island A variant was also identified. Conclusions: The presence
      of a 'hitch-hiking' blaGES-6-harbouring In1076 integron in an ICE and an exoU
      carrying genomic island highlight the potential spread of these elements through
      conjugation and/or clonal expansion of the ST235 lineage.

PMID- 29029084
TI  - Penicillin-binding protein encoded by pbp4 is involved in mediating copper stress
      in Listeria monocytogenes.
AB  - Listeria monocytogenes raises major food safety and public health concerns due to
      its potential for severe foodborne disease and persistent colonization of food
      processing facilities. Copper is often employed to control pathogens in
      agriculture and is increasingly used in healthcare facilities, but mechanisms
      mediating tolerance of L. monocytogenes to copper remain poorly understood. A
      mariner-based mutant library of L. monocytogenes 2011L-2858, implicated in the
      2011 listeriosis outbreak via whole cantaloupe, was screened for growth at
      sublethal levels of copper yielding mutant G2B4 with decreased copper tolerance.
      The transposon was localized in pbp4 (lmo2229 homolog), encoding a penicillin
      binding protein (PBP). In addition to reduced copper tolerance, G2B4 exhibited
      increased susceptibility to beta-lactam antibiotics, reduced biofilm formation
      and reduced virulence in the Galleria mellonella model. Mutant phenotypes were
      fully restored upon genetic complementation of G2B4 with intact pbp4. Findings
      provide the first evidence for the role of a PBP in copper tolerance of L.
      monocytogenes and suggest that pbp4 may be a suitable target to enable the use of
      lower levels of copper or enhance the effectiveness of levels currently in use.
      Given the wide distribution of PBPs and their highly conserved nature, this could
      have profound impacts in regard to ecology and control of L. monocytogenes and
      other microorganisms.

PMID- 29029085
TI  - Impairment of elastic properties of the aorta in bicuspid aortic valve:
      relationship between biomolecular and aortic strain patterns.
AB  - Aims: Bicuspid aortic valve (BAV) is associated with aortic wall alterations. We
      aimed to detect any correlation between aortic elasticity and genetic and
      biomolecular patterns of elastin. Methods and results: Forty-nine BAV patients
      (mean age: 38 +/- 17.05) were prospectively enrolled. A blood sample was drawn
      for analysis of a single nucleotide polymorphism of elastin gene (ELN rs2071307)
      responsible for misfolding of elastin, and for the amount of elastin soluble
      fragments (ESF) in the plasma. Aortic dimensions and elastic properties were
      determined by echocardiography, aortic stiffness (AS) by M-mode analysis, and
      longitudinal strain (LS) of the ascending aorta (AA) by speckle-tracking
      echocardiography; values of aortic strain were compared with 45 age-matched
      subjects (mean age: 33 +/- 9.67) with tricuspid aortic valve (TAV). BAV patients
      had greater aortic dimensions [Valsalva sinus (P = 0.004), sinotubular junction
      (P = 0.013), AA (P < 0.001)] and stiffness (P = 0.002) but lower LS (P = 0.04)
      than those with TAV. Results from comparisons of mutated genotype patients (AA, n
      = 10) with heterozygous (GA, n = 21) and wild-types ones (GG, n = 16) revealed
      that the presence of mutation was associated with increased ESF (P = 0.010 GG vs.
      GA; P = 0.035 GA vs. AA), larger AA (P = 0.019 GG vs. GA; P = 0.001 GG vs. AA),
      and lower LS (P = 0.032 GG vs. AA). Patients with a dilated AA showed greater ESF
      (P < 0.001), greater AS (P = 0.007), and lower LS of the AA (P = 0.002) than
      those with a normal AA. The same parameters were not significantly different
      comparing patients with moderate or severe aortic valve disease and patients with
      less than moderate valve disease. Conclusions: Our results show a close
      correlation between genetic and biomolecular patterns of elastin and mechanical
      properties of the aorta in patients with BAV.

PMID- 29029086
TI  - HIV prevention costs and their predictors: evidence from the ORPHEA Project in
      Kenya.
AB  - We estimate costs and their predictors for three HIV prevention interventions in
      Kenya: HIV testing and counselling (HTC), prevention of mother-to-child
      transmission (PMTCT) and voluntary medical male circumcision (VMMC). As part of
      the 'Optimizing the Response of Prevention: HIV Efficiency in Africa' (ORPHEA)
      project, we collected retrospective data from government and non-governmental
      health facilities for 2011-12. We used multi-stage sampling to determine a sample
      of health facilities by type, ownership, size and interventions offered totalling
      144 sites in 78 health facilities in 33 districts across Kenya. Data sources
      included key informants, registers and time-motion observation methods. Total
      costs of production were computed using both quantity and unit price of each
      input. Average cost was estimated by dividing total cost per intervention by
      number of clients accessing the intervention. Multivariate regression methods
      were used to analyse predictors of log-transformed average costs. Average costs
      were $7 and $79 per HTC and PMTCT client tested, respectively; and $66 per VMMC
      procedure. Results show evidence of economies of scale for PMTCT and VMMC:
      increasing the number of clients per year by 100% was associated with cost
      reductions of 50% for PMTCT, and 45% for VMMC. Task shifting was associated with
      reduced costs for both PMTCT (59%) and VMMC (54%). Costs in hospitals were higher
      for PMTCT (56%) in comparison to non-hospitals. Facilities that performed testing
      based on risk factors as opposed to universal screening had higher HTC average
      costs (79%). Lower VMMC costs were associated with availability of male
      reproductive health services (59%) and presence of community advisory board
      (52%). Aside from increasing production scale, HIV prevention costs may be
      contained by using task shifting, non-hospital sites, service integration and
      community supervision.

PMID- 29029088
TI  - Plant-Herbivore and Plant-Pollinator Interactions of the Developing Perennial
      Oilseed Crop, Silphium integrifolium.
AB  - Sampling in Kansas and North Dakota documented the plant-herbivore and plant
      pollinator interactions of the developing perennial oilseed crop, Silphium
      integrifolium Michx. The larva of the tortricid moth, Eucosma giganteana (Riley),
      was the most damaging floret- and seed-feeding pest in Kansas, with infested
      heads producing ~85% (2015) or ~45% (2016) fewer seeds than apparently undamaged
      heads. Necrosis of apical meristems caused stunting and delayed bloom in Kansas;
      though the source of the necrosis is not known, observations of the tarnished
      plant bug, Lygus lineolaris (Palisot de Beauvois; Hemiptera: Miridae), in S.
      integrifolium terminals suggest a possible cause. In North Dakota, E. giganteana
      larvae were not found, but pupae of Neotephritis finalis (Loew; Diptera:
      Tephritidae), a minor pest of cultivated sunflower, were common in the heads of
      S. integrifolium. Bees appeared highly attracted to S. integrifolium, and in all
      but one observation, bees were seen actively collecting pollen. The most common
      bees included large apids (Apis mellifera L., Svastra obliqua [Say], Melissodes
      spp.) and small-bodied halictids (Lasioglossum [Dialictus] spp.). Controlled
      pollination experiments demonstrated that S. integrifolium is pollinator
      dependent, due to both mechanical barriers (imperfect florets and protogyny) and
      genetic self-incompatibility. Subsequent greenhouse tests and AFLP confirmation
      of putative self-progeny show that a low (<1%) level of self-pollination is
      possible. If genetic self-incompatibility is eventually reduced through breeding,
      mechanical barriers would maintain a reliance on bees to move pollen between male
      and female florets. Collectively, observations on S. integrifolium show that both
      herbivore and pollinator management are important to maximize seed production.

PMID- 29029089
TI  - Geostatistics and Geographic Information System to Analyze the Spatial
      Distribution of the Diversity of Anastrepha Species (Diptera: Tephritidae): the
      Effect of Forest Fragments in an Urban Area.
AB  - Fruit flies are among the most damaging insect pests of commercial fruit in
      Brazil. It is important to understand the landscape elements that may favor these
      flies. In the present study, spatial data from surveys of species of Anastrepha
      Schiner (Diptera: Tephritidae) in an urban area with forest fragments were
      analyzed, using geostatistics and Geographic Information System (GIS) to map the
      diversity of insects and evaluate how the forest fragments drive the spatial
      patterns. The results indicated a high diversity of species associated with large
      fragments, and a trend toward lower diversity in the more urbanized area, as the
      fragment sizes decreased. We concluded that the diversity of Anastrepha species
      is directly and positively related to large and continuous forest fragments in
      urbanized areas, and that combining geostatistics and GIS is a promising method
      for use in insect-pest management and sampling involving fruit flies.

PMID- 29029087
TI  - The effect of sacubitril/valsartan compared to olmesartan on cardiovascular
      remodelling in subjects with essential hypertension: the results of a randomized,
      double-blind, active-controlled study.
AB  - Aims: Progressive aortic stiffening eventually leads to left ventricular (LV)
      hypertrophy and heart failure if left untreated. Anti-hypertensive agents have
      been shown to reverse this to some extent. The effects of sacubitril/valsartan
      (LCZ696), a dual-action angiotensin receptor blocker (ARB), and neprilysin
      inhibitor, on arterial stiffness and LV remodelling have not been investigated.
      Methods and results: This was a randomized, multi-centre, double-blind, double
      dummy, active-controlled, parallel group, study to compare the effects on
      cardiovascular remodelling of sacubitril/valsartan with those of olmesartan in
      patients with hypertension and elevated pulse pressure. Magnetic resonance
      imaging scans were used to assess LV mass and local aortic distensibility, at
      baseline and at 12 and 52 weeks after initiation of treatment. Central pulse and
      systolic pressure were determined using a SphymoCor(r) XCEL device at each time
      point. A total of 114 patients were included, with 57 in each treatment group.
      The mean age was 59.8 years, and 67.5% were male. Demographic characteristics did
      not vary between the two sets of patients. Left ventricular mass index decreased
      to a greater extent in the sacubitril/valsartan group compared to the olmesartan
      group from baseline to 12 weeks (-6.36 vs. -2.32 g/m2; P = 0.039) and from
      baseline to 52 weeks (-6.83 vs. -3.55 g/m2; P = 0.029). These differences
      remained significant after adjustment for systolic blood pressure (SBP) at follow
      up (P = 0.036 and 0.019 at 12 and 52 weeks, respectively) and similar signals
      (though formally non-significant) were observed after adjusting for changes in
      SBP (P = 0.0612 and P = 0.0529, respectively). There were no significant
      differences in local distensibility changes from baseline to 12 or 52 weeks
      between the two groups; however, there was a larger reduction in central pulse
      pressure for the sacubitril/valsartan group compared to the olmesartan group (P =
      0.010). Conclusion: Since LV mass change correlates with cardiovascular
      prognosis, the greater reductions in LV mass indicate valuable advantages of
      sacubitril/valsartan compared to olmesartan. The finding that LV mass index
      decrease might be to some extent independent of SBP suggests that the effect of
      the dual-acting agent may go beyond those due to its BP-lowering ability.

PMID- 29029090
TI  - Comparative Toxicities of Newer and Conventional Insecticides: Against Four
      Generalist Predator Species.
AB  - Generalist insect predators play an essential role in regulating the populations
      of Bemisia tabaci and other pests in agricultural systems, but may be affected
      negatively by insecticides applied for pest management. Evaluation of insecticide
      compatibility with specific predator species can provide a basis for making
      treatment decisions with the aim of conserving natural enemies. Eleven
      insecticides representing six modes of action groups were evaluated for toxicity
      against four predator species and at different developmental stages. Full
      concentration series bioassays were conducted on laboratory-reared or insectary
      supplied predators using Petri dish and systemic uptake bioassay techniques.
      Highest toxicities were observed with imidacloprid and clothianidin against first
      and second instar nymphs of Geocoris punctipes (Say) (Hemiptera: Geocoridae).
      Later instar nymphs were less susceptible to neonicotinoid treatments based on
      higher LC50s observed with imidacloprid, thiamethoxam, and dinotefuran against
      third or fourth instar nymphs. The pyrethroid insecticide bifenthrin was highly
      toxic against adults of G. punctipes and Orius insidiosus (Say) (Hemiptera:
      Anthocoridae). Standard concentration/mortality evaluation of nonacute toxicity
      insecticides, including buprofezin, pyriproxyfen, spirotetramat, and
      spiromesifen, was inconclusive in terms of generating probit statistics. However,
      low mortality levels of insects exposed for up to 120 h suggested minimal
      lethality with the exception of pyriproxyfen that was mildly toxic to Chrysoperla
      rufilabris (Burmeister) (Neuroptera: Chrysopidae).

PMID- 29029092
TI  - CORRIGENDUM FOR "Dapagliflozin Lowers Plasma Glucose Concentration and Improves
      beta-Cell Function".

PMID- 29029091
TI  - Cockroach Oothecal Parasitoid, Evania appendigaster (Hymenoptera: Evaniidae)
      Exhibits Oviposition Preference Towards Oothecal Age Most Vulnerable to Host
      Cannibalism.
AB  - Many female parasitoid wasps optimize host selection to balance the benefits of
      high-quality hosts and the costs of predator- or hyperparasitoid-induced
      mortality risks to maximize their fitness. Cannibalism exists in many insect
      species and affects survival of parasitoid larvae developing in or on parasitized
      hosts. However, little is known about how parasitoid wasps resolve the fitness
      consequence of host cannibalism-induced mortality risk during host selection. We
      examined the effect of oothecal age on cannibalism in the American cockroach
      Periplaneta americana (L.) (Dictyoptera: Blattidae) and its effect on host age
      selection and fitness of its oothecal parasitoid Evania appendigaster (L.)
      (Hymenoptera: Evaniidae). P. americana differentially cannibalized 1-d-old (30
      60%) versus 10- to 40-d-old oothecae (<9%). However, parasitoid females did not
      avoid but still preferred to parasitize 1-d-old (45%) over 10- to 40-d-old
      oothecae (1.6-20%). The parasitism rate was greater and the handling time was
      shorter on 1-d-old compared to older oothecae. For parasitoid progeny emerging
      from different-aged oothecae, regression analysis showed that development time
      increased and body size (measured as hind tibia length) and longevity decreased
      with oothecal age. These results demonstrate that reduced parasitoid progeny
      survival due to host cannibalism did not change the parasitoid's oviposition
      preference for newly laid oothecae, and that E. appendigaster females traded
      progeny survival for fitness gains for themselves and their progeny.

PMID- 29029093
TI  - Electronegative Low-Density Lipoprotein L5 Induces Adipose Tissue Inflammation
      Associated With Metabolic Syndrome.
AB  - Context: Electronegative low-density lipoprotein (LDL) L5 is a naturally
      occurring, atherogenic entity found at elevated levels in the plasma of patients
      with metabolic syndrome (MetS) in the absence of elevated plasma LDL levels.
      Objective: To investigate the role of L5 in the mechanism of adipose tissue
      inflammation associated with MetS. Patients/Setting: Plasma LDL isolated from
      patients with MetS (n = 29) and controls (n = 29) with similar plasma LDL levels
      was separated into five subfractions, L1 to L5, with increasing
      electronegativity. Design: We examined the invivo effects of L5 on adipose tissue
      in mice and the in vitro effects of L5 on adipocytokine signaling and monocytes.
      Results: Tail-vein injection of human L5 but not L1 into C57BL/6 mice induced the
      accumulation of F4/80+ and CD11c+ M1 macrophages. The effects of L5 were
      attenuated in mice deficient for L5's receptor, lectin-like oxidized LDL receptor
      1 (LOX-1). L5 but not L1 induced human adipocytes to release inflammatory
      adipocytokines. Incubating human THP-1 monocytes with LDL-free culture media from
      L5-treated adipocytes enhanced the migration of monocytes by 300-fold (P < 0.001
      vs L1-treated adipocyte media)-effects that were attenuated by LOX-1 neutralizing
      antibody. Migrated cells were positive for mature macrophage marker PM-2K,
      indicating the transformation of monocytes into macrophages. The infiltration of
      M1 macrophages in adipose tissue was also observed in a previously established
      hamster model of endogenously elevated L5. Conclusions: L5 induces adipose
      inflammation through LOX-1 by promoting macrophage maturation and infiltration
      into adipose tissue. Elevated plasma L5 levels may be a novel etiology of adipose
      tissue inflammation in patients with MetS.

PMID- 29029094
TI  - Thyroid Hormone Metabolism Defects in a Mouse Model of SBP2 Deficiency.
AB  - Selenocysteine insertion sequence binding protein 2 (SBP2) is an essential factor
      in selenoprotein synthesis. Patients with SBP2 defects have a characteristic
      thyroid phenotype and additional manifestations such as growth delay, male
      infertility, impaired motor coordination, and developmental delay. The thyroid
      phenotype has become pathognomonic for this defect, and putative deficiencies in
      the iodothyronine deiodinases selenoenzymes have been implicated. To investigate
      the role of SBP2 and selenoproteins in thyroid physiology and answer questions
      raised by the human syndrome, we generated a tamoxifen-inducible Sbp2 conditional
      knockout (iCKO) mouse model. These Sbp2-deficient mice have high serum thyroxine
      (T4), thyrotropin, and reverse triiodothyronine (T3), similar to the human
      phenotype of SBP2 deficiency, whereas serum T3 is normal. Their liver T4 and T3
      content reflect the serum levels, and deiodinase 1 expression and enzymatic
      activity were decreased. In contrast, brain T3 content is decreased, indicative
      of local hypothyroidism, confirmed by the decreased expression of the thyroid
      hormone (TH) positively regulated gene hairless. Interestingly, the cerebrum T4
      content did not parallel the high serum T4 levels, and the expression of TH
      transporters was decreased. Deiodinase 2 enzymatic activity and deiodinase 3
      expression were decreased in cerebrum. The expression and/or activity of other
      selenoproteins were decreased in brain, liver, and serum, thus demonstrating a
      global deficiency in selenoprotein synthesis. Sbp2 iCKO mice replicate the
      thyroid phenotype of SBP2 deficiency and represent an important tool to advance
      our understanding of the role of SBP2 in thyroid homeostasis and for
      investigating selenoprotein biology relevant to human disease.

PMID- 29029095
TI  - Identification of novel bifunctional HIV-1 reverse transcriptase inhibitors.
AB  - Objectives: The increasing prevalence of mutations in HIV-1 reverse transcriptase
      (RT) that confer resistance to existing NRTIs and NNRTIs underscores the need to
      develop RT inhibitors with novel mode-of-inhibition and distinct resistance
      profiles. Methods: Biochemical assays were employed to identify inhibitors of RT
      activity and characterize their mode of inhibition. The antiviral activity of the
      inhibitors was assessed by cell-based assays using laboratory HIV-1 isolates and
      MT4 cells. RT variants were purified via avidin affinity columns. Results:
      Compound A displayed equal or greater potency against many common NNRTI-resistant
      RTs (K103N and Y181C RTs) relative to WT RT. Despite possessing certain NNRTI
      like properties, such as being unable to inhibit an engineered variant of RT
      lacking an NNRTI-binding pocket, we found that compound A was dependent on Mg2+
      for binding to RT. Optimization of compound A led to more potent analogues, which
      retained similar activities against WT and K103N mutant viruses with
      submicromolar potency in a cell-based assay. One of the analogues, compound G,
      was crystallized in complex with RT and the structure was determined at 2.6 A
      resolution. The structure indicated that compound G simultaneously interacts with
      the active site (Asp186), the highly conserved primer grip region (Leu234 and
      Trp229) and the NNRTI-binding pocket (Tyr188). Conclusions: These findings reveal
      a novel class of RT bifunctional inhibitors that are not sensitive to the most
      common RT mutations, which can be further developed to address the deficiency of
      current RT inhibitors.

PMID- 29029096
TI  - Novel roles of glycosaminoglycans in the degradation of type I collagen by
      cathepsin K.
AB  - Glycosaminoglycans (GAGs) and collagen are the major organic components of bone
      matrix. However, their roles and functional relationships remain elusive. To
      investigate the role of GAGs in bone matrix degradation, the effects of GAGs on
      collagen were examined under acidic conditions that recapitulate the
      microenvironment of osteoclast resorption pits. We found that sulfated GAGs
      protect collagen fibrils against acid denaturation. Scanning electron microscopy
      demonstrated that collagen fibrils retain the fibril structure at pH 4.0 in the
      presence of chondroitin 6-sulfate. By surface plasmon resonance analysis, we
      found that sulfated GAGs, but not non-sulfated GAGs, bind to triple-helix type I
      collagen below pH 4.5. The binding of collagen in an acidic solution was
      dependent upon the GAG sugar chain length. Functionally, the acid-resistant
      collagen fibrils generated in the presence of sulfated GAGs were resistant to
      cathepsin K degradation in vitro below pH 4.0. As the pH increased from 4.0 to
      5.0, the acid-resistant collagen fibrils were degraded by cathepsin K. Our
      results highlight the possibility that the interaction between GAGs and collagen
      under acidic conditions has a regulatory impact on cathepsin K-mediated bone
      degradation.

PMID- 29029097
TI  - Impact of Three Doses of Vitamin D3 on Serum 25(OH)D Deficiency and Insufficiency
      in At-Risk Schoolchildren.
AB  - Objective: We investigated the daily dose of vitamin D needed to achieve serum 25
      hydroxyvitamin D [25(OH)D] sufficiency among schoolchildren at risk for
      deficiency. Study Design: The Daily D Health Study was a randomized double-blind
      vitamin D supplementation trial among racially/ethnically diverse schoolchildren
      (n = 685) in the northeastern United States. Children were supplemented with
      vitamin D3 at 600, 1000, or 2000 IU/d for 6 months. Measurements included serum
      25(OH)D at baseline (October to December), 3 months (January to March), 6 months
      (April to June), and 12 months (6 months after supplementation). Results: At
      baseline, mean +/- standard deviation serum 25(OH)D level was 22.0 +/- 6.8 ng/mL,
      with 5.5% severely vitamin D deficient (<12 ng/mL), 34.1% deficient (12 to 19
      ng/mL), 49.0% insufficient (20 to 29 ng/mL), and 11.4% sufficient (>=30 ng/mL).
      The lowest levels of serum 25(OH)D were found among black (17.9 +/- 6.7 ng/mL)
      and Asian children (18.9 +/- 4.8 ng/mL), with no baseline differences by weight
      status. Serum 25(OH)D increased over 6 months in all three dose groups. The 2000
      IU/d group achieved a higher mean serum 25(OH)D level than the other two dose
      groups (33.1 vs 26.3 and 27.5 ng/mL; P < 0.001), with 59.9% of this group
      attaining sufficiency at 3 months and only 5.3% remaining severely
      deficient/deficient at 6 months. All dose groups demonstrated a fall in 25(OH)D
      at 12 months. Conclusions: Children at risk for vitamin D deficiency benefited
      from daily sustained supplementation of 2000 IU/d compared with lower doses
      closer to the current recommended daily allowance for vitamin D intake. This
      benefit occurred over the winter months, when serum 25(OH)D level tend to fall.

PMID- 29029098
TI  - Genital Granulomatosis in Male and Female Patients With Crohn's Disease: Clinical
      Presentation and Treatment Outcomes.
AB  - Background: Genital granulomatosis [GG] is a metastatic form of Crohn's disease
      [CD], characterised by granulomatous inflammation of the genital skin without
      contact with the gastrointestinal tract. Little is known about GG, as most
      publications are case reports or small series, and only sporadic in male cases.
      Methods and Aims: Cases of GG were retrospectively collected through the
      Collaborative Network For Exceptionally Rare case reports project of the European
      Crohn's and Colitis Organisation. Results: A total of 43 patients [9 males, 34
      females] were diagnosed as having GG, mostly as oedema and/or ulcers.
      Histological confirmation of granulomas was obtained in 70% of the cases. CD
      location was colonic or ileocolonic in 97% and perianal disease was documented in
      57%. There was no significant difference between males and females in CD
      phenotype or genital lesions. GG was the first manifestation of inflammatory
      bowel disease [IBD] in one-third of the patients; these patients were younger at
      the time of GG occurrence and they all were non-smokers. GG occurred in the
      absence of gastrointestinal disease activity in 30% of the cases. Ten out of 11
      patients [91%] responded to systemic corticosteroid treatment, 5/9 patients
      responded to immunomodulators, and 9/11 patients responded to anti-tumour
      necrosis factor alpha [TNF-alpha] agents. Conclusions: GG is a rare
      extraintestinal manifestation of CD. It mainly occurs among women, in the setting
      of colonic involvement of CD, and perianal disease is often associated. Most
      cases are successfully managed with systemic corticosteroids or anti-TNF agents.

PMID- 29029100
TI  - 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac
      surgery.

PMID- 29029101
TI  - Growth Outcomes After GH Therapy of Patients Given Long-Term Corticosteroids for
      Juvenile Idiopathic Arthritis.
AB  - Context: Growth hormone (GH) therapy may improve statural growth outcomes in
      patients with severe juvenile idiopathic arthritis (JIA). Objectives: To evaluate
      the effect of GH treatment on adult height and to identify determinants of growth
      outcomes in JIA. Design and Patients: Data from 58 patients with JIA, including
      53 receiving GH, enrolled in three prospective clinical trials between 1997 and
      2002 were analyzed. Intervention: GH (0.056 mg/kg/d [interquartile range (IQR),
      0.050 to 0.062]) for a median duration of 6.5 years (IQR, 4.7 to 7.9 years). Main
      Outcome Measures: Factors associated with a favorable growth outcome (adult
      height - target height <= -1.5 standard deviations) were identified by
      multivariate logistic regression. Results: Adult height was available for 48
      patients 8.6 years after GH initiation (IQR, 6.0 to 10.2 years). Height standard
      deviation score (SDS) increased from -2.9 (IQR, -4.4 to -1.6) at baseline to -1.7
      (IQR, -3.9 to -0.1) in adulthood (P < 0.001). Median adult height was below
      target height [SDS, -0.2 (IQR, -1.4 to 0.4); P < 0.001]. Corrected adult height
      SDS was -1.3 (IQR, -3.0 to -0.2). Growth outcome was favorable in 24 (52.2%)
      patients. Significant independent determinants of growth outcome were age at GH
      initiation [adjusted odds ratio (aOR), 0.68 per additional year; 95% confidence
      interval (CI), 0.47 to 0.99], height at GH initiation (aOR, 2.6 per additional
      SDS; 95% CI, 1.15 to 5.9), and mean C-reactive protein levels during follow up
      (aOR, 0.51 per additional 10 mg/L; 95% CI, 0.28 to 0.92). Conclusion: Long-term
      GH treatment significantly increased growth in patients with JIA but did not
      fully restore the genetic growth potential. The response showed marked
      interindividual variability and was weaker in patients with severe inflammation.

PMID- 29029099
TI  - Biomarkers of Mineral and Bone Metabolism and 20-Year Risk of Hospitalization
      With Infection: The Atherosclerosis Risk in Communities Study.
AB  - Context: Mineral and bone disorders (MBDs) might be relevant in the etiology of
      infection. Objective: To determine whether MBD biomarkers were associated with
      the incidence of hospitalization with infection. We also assessed the cross
      sectional association between MBD biomarker levels and kidney function. Design,
      Setting, Participants: Community-based cohort study of 11,218 participants with
      an estimated glomerular filtration rate (eGFR) >=30 mL/min/1.73m2 in the
      Atherosclerosis Risk in Communities study. We assessed the cross-sectional
      associations of five MBD markers-fibroblast growth factor 23 (FGF23), 25
      hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), calcium corrected for
      hypoalbuminemia, and phosphorus-with eGFR from 1990 to 1992 and their
      longitudinal associations with incident hospitalization with infection in 1990 to
      2013. Main Outcome: Incident hospitalization with infection. Results: In age-,
      sex-, and race-adjusted models, lower eGFRs were significantly associated with
      greater levels of FGF23, PTH, and corrected calcium but not 25(OH)D or
      phosphorus. During follow-up, 5078 hospitalizations with infection occurred. In
      fully adjusted Cox models, with the second quartile as the reference, the hazard
      ratio (HR) was significantly greater in the highest quartile of FGF23 [HR, 1.12;
      95% confidence interval (CI), 1.03 to 1.21], PTH (HR, 1.09; 95% CI, 1.01 to
      1.18), and corrected calcium (HR, 1.11; 95% CI, 1.03 to 1.20), and lowest
      quartile for 25(OH)D (HR, 1.11; 95% CI, 1.03 to 1.21). The association with
      phosphorus was significant only when the outcome was restricted to primary
      diagnosis of infection. These findings were consistent across subgroups of age,
      sex, race, and eGFR (<60 vs >=60 mL/min/1.73 m2). Conclusions: MBD biomarkers
      were associated with eGFR and the subsequent risk of infection, supporting MBD
      involvement in the etiology of infection.

PMID- 29029104
TI  - Adoptive Immunotherapy of Viral Infections: Should Infectious Disease Embrace
      Cellular Immunotherapy?

PMID- 29029103
TI  - Cardiovascular Disease Prevention Policy in Human Immunodeficiency Virus:
      Recommendations From a Modeling Study.
AB  - Background: Cardiovascular disease (CVD) is expected to contribute a large
      noncommunicable disease burden among human immunodeficiency virus (HIV)-infected
      people. We quantify the impact of prevention interventions on annual CVD burden
      and costs among HIV-infected people in the Netherlands. Methods: We constructed
      an individual-based model of CVD in HIV-infected people using national ATHENA
      (AIDS Therapy Evaluation in The Netherlands) cohort data on 8791 patients on
      combination antiretroviral therapy (cART). The model follows patients as they
      age, develop CVD (by incorporating a CVD risk equation), and start cardiovascular
      medication. Four prevention interventions were evaluated: (1) increasing the rate
      of earlier HIV diagnosis and treatment; (2) avoiding use of cART with increased
      CVD risk; (3) smoking cessation; and (4) intensified monitoring and drug
      treatment of hypertension and dyslipidemia, quantifying annual number of averted
      CVDs and costs. Results: The model predicts that annual CVD incidence and costs
      will increase by 55% and 36% between 2015 and 2030. Traditional prevention
      interventions (ie, smoking cessation and intensified monitoring and treatment of
      hypertension and dyslipidemia) will avert the largest number of annual CVD cases
      (13.1% and 20.0%) compared with HIV-related interventions-that is, earlier HIV
      diagnosis and treatment and avoiding cART with increased CVD risk (0.8% and 3.7%,
      respectively)-as well as reduce cumulative CVD-related costs. Targeting high-risk
      patients could avert the majority of events and costs. Conclusions: Traditional
      CVD prevention interventions can maximize cardiovascular health and defray future
      costs, particularly if targeting high-risk patients. Quantifying additional
      public health benefits, beyond CVD, is likely to provide further evidence for
      policy development.

PMID- 29029102
TI  - Nucleos(t)ide Analogue Treatment for Patients With Hepatitis B Virus (HBV) e
      Antigen-Positive Chronic HBV Genotype C Infection: A Nationwide, Multicenter,
      Retrospective Study.
AB  - Background: Antiviral treatment for hepatitis B virus (HBV) e antigen (HBeAg)
      positive chronic HBV infection is still controversial. We assessed whether
      antiviral treatment reduces the risk of liver disease progression in these
      patients. Methods: This study included consecutive patients in 8 large-volume
      hospitals in Korea who tested positive for HBeAg and had an HBV DNA level of
      >20000 IU/mL, an alanine aminotransferase (ALT) level of <40 IU/L, and no
      evidence of cirrhosis. The primary end point was the development of
      hepatocellular carcinoma (HCC), and the secondary end point was the development
      of cirrhosis. Results: A total of 484 patients were included: 87 were in the
      antiviral treatment group, and 397 were in the control group. Baseline liver
      function was significantly more favorable for the control group. After matching
      for propensity score to overcome those differences, the antiviral treatment group
      had a significantly reduced risk for HCC (hazard ratio [HR], 0.234; log-rank P =
      .046) and cirrhosis (HR, 0.235; log-rank P = .015), compared with the control
      group. After balancing the baseline characteristics by using inverse probability
      weighting, antiviral therapy significantly decreased the risk of HCC (HR, 0.189;
      log-rank P = .004) and cirrhosis (HR, 0.347; log-rank P = .036). Conclusion:
      Antiviral therapy for patients with HBeAg-positive chronic HBV infection and have
      a high HBV load reduces the risk of HCC, even if the ALT level is below the upper
      limit of normal.

PMID- 29029105
TI  - Comparative performance of transcatheter aortic valve-in-valve implantation
      versus conventional surgical redo aortic valve replacement in patients with
      degenerated aortic valve bioprostheses: systematic review and meta-analysis.
AB  - The objective of this report was to directly compare, by means of a systematic
      review and meta-analysis, redo surgical aortic valve replacement (re-sAVR) with
      valve-in-valve transcatheter aortic valve implantation (ViV TAVI) for patients
      with failed degenerated aortic bioprostheses. Multiple databases were screened
      for all available reports comparing ViV TAVI with re-sAVR in patients with
      failing degenerated aortic bioprostheses. The primary outcome was all-cause
      mortality determined from the longest available survival data. Five observational
      studies (n = 342) were included in the meta-analysis; patients in the ViV TAVI
      group were older and had a higher baseline risk compared to those in the re-sAVR
      group. Although there was no statistical difference in procedural mortality [risk
      ratio (RR) 0.74, 95% confidence interval (CI) 0.18-2.97; P = 0.67], 30-day
      mortality (RR 1.29, 95% CI 0.44-3.78; P = 0.64) and cardiovascular mortality (RR
      0.91, 95% CI 0.30-2.70; P = 0.86) at a mean follow-up period of 18 months,
      cumulative survival analysis favoured surgery with borderline statistical
      significance (ViV TAVI versus re-sAVR: hazard ratio 1.91, 95% CI 1.03-3.57; P =
      0.039). ViV TAVI was associated with a significantly lower rate of permanent
      pacemaker implantations (RR 0.37, 95% CI 0.20-0.68; P = 0.002) and shorter
      intensive care unit (P < 0.001) and hospital stays (P = 0.020). In contrast, re
      sAVR offered superior echocardiographic outcomes: lower incidence of patient
      prosthesis mismatch (P = 0.008), fewer paravalvular leaks (P = 0.023) and lower
      mean postoperative aortic valve gradients in the prespecified analysis (P =
      0.017). The ViV TAVI approach is a safe and feasible alternative to re-sAVR that
      may offer an effective, less invasive treatment for patients with failed surgical
      aortic valve bioprostheses who are inoperable or at high risk. Re-sAVR should
      remain the standard of care, particularly in the low-risk population, because it
      offers superior haemodynamic outcomes with low mortality rates.

PMID- 29029106
TI  - Iatrogenic Cushing Syndrome in a Child With Congenital Adrenal Hyperplasia:
      Erroneous Compounding of Hydrocortisone.
AB  - Context: Patients with 21-hydroxylase deficiency congenital adrenal hyperplasia
      (CAH) require lifelong treatment with glucocorticoids. In growing children, the
      drug of choice is hydrocortisone. Commercially available hydrocortisone tablets
      do not conform to very low doses prescribed to infants and toddlers, and
      compounded hydrocortisone is often dispensed to meet therapeutic needs. However,
      safety, efficacy, and uniformity of compounded products are not tested. We report
      a case of Cushing syndrome in a child with CAH who was inadvertently receiving
      excessive hydrocortisone in compounded form. Design: A 20-month-old girl with CAH
      developed growth deceleration, excessive weight for length, irritability,
      increased facial fat, plethora, and excess body hair while receiving
      hydrocortisone from a local compounding pharmacy. The signs and symptoms
      persisted despite decreasing hydrocortisone dose. Iatrogenic Cushing syndrome was
      suspected. The prescribed hydrocortisone capsules were sent for analysis to the
      Sports Medicine Research & Testing Laboratory, where testing revealed that each 1
      mg hydrocortisone capsule contained five to 10 times the dose prescribed and
      listed on the label. Conclusion: Physicians must be aware that errors in
      compounded medications may lead to unanticipated adverse effects. Iatrogenic
      Cushing syndrome should be suspected in any child receiving compounded
      glucocorticoid treatment who develops growth arrest and excess weight gain.

PMID- 29029107
TI  - New Food Baits for Trapping German Cockroaches, Blattella germanica (L.)
      (Dictyoptera: Blattellidae).
AB  - German cockroaches (GCRs), Blattella germanica (L.) (Dictyoptera: Blattellidae),
      are attracted to those beer semiochemicals (e.g., ethanol) that formerly living
      and active yeasts have produced or otherwise formed in the brewing process. We
      predicted that an earlier step in the production of beer, where yeasts actively
      metabolize the sugar in malted barley powder (dry malt extract [DME]), is very
      attractive to GCRs. In laboratory experiments, a 3-component composition (3CC)
      comprising DME, water, and Brewer's yeast strongly attracted GCR nymphs, females,
      and males. Both Brewers' yeast and 'spoilage organisms' in the DME or water seem
      to add to the attractiveness of the 3CC, but there is no additive or synergistic
      effect between them. The 3CC becomes optimally attractive to GCRs after 12 h of
      fermentation and stays that attractive for at least 120 h. In field trapping
      experiments, the 3CC and-unexpectedly-also the DME each proved as effective for
      attracting and capturing GCRs as a commercial cockroach bait (Combat Roach Gel).
      Future studies will investigate lethal biocontrol agents that can be added to the
      3CC, or the DME, and will explore the efficacy of such lethal baits for GCR
      control.

PMID- 29029108
TI  - Relative Risks of Contributing Factors to Morbidity and Mortality in Adults With
      Craniopharyngioma on Growth Hormone Replacement.
AB  - Context: In adults, craniopharyngioma (CP) of either childhood-onset (CO-CP) or
      adult-onset (AO-CP) is associated with increased morbidity and mortality, but
      data on the relative risks (RRs) of contributing factors are lacking. Objective:
      To assess the RRs of factors contributing to morbidity and mortality in adults
      with CO-CP and AO-CP. Methods: Data on 1669 patients with CP from KIMS (Pfizer
      International Metabolic Database) were analyzed using univariate and multiple
      Poisson and Cox regression methods. Results: When CO-CP and AO-CP groups were
      combined, history of stroke and hyperlipidemia increased cardiovascular risk,
      higher body mass index (BMI) and radiotherapy increased cerebrovascular risk, and
      increased waist circumference increased the risk of developing diabetes mellitus
      (DM). Compared with patients with CO-CP, patients with AO-CP had a threefold
      higher risk of tumor recurrence, whereas being female and previous radiotherapy
      exposure conferred lower risks. Radiotherapy and older age with every 10 years
      from disease onset conferred a 2.3- to 3.5-fold risk for developing new
      intracranial tumors, whereas older age, greater and/or increasing BMI, history of
      stroke, and lower insulinlike growth factor I (IGF-I) standard deviation score
      measured at last sampling before death were related to increased all-cause
      mortality. Compared with the general population, adults with CP had 9.3-, 8.1-,
      and 2.2-fold risks of developing DM, new intracranial tumors, and early death,
      respectively. Conclusion: Conventional factors that increase the risks of cardio-
      and cerebrovascular diseases and DM and risks for developing new intracranial
      tumors contributed to excess morbidity and mortality. In addition, lower serum
      IGF-I level measured from the last sample before death was inversely associated
      with mortality risk in patients with CP.

PMID- 29029110
TI  - 2017 EACTS Guidelines on perioperative medication in adult cardiac surgery.

PMID- 29029109
TI  - Early diagnosis of acute coronary syndrome.
AB  - The diagnostic evaluation of acute chest pain has been augmented in recent years
      by advances in the sensitivity and precision of cardiac troponin assays, new
      biomarkers, improvements in imaging modalities, and release of new clinical
      decision algorithms. This progress has enabled physicians to diagnose or rule-out
      acute myocardial infarction earlier after the initial patient presentation,
      usually in emergency department settings, which may facilitate prompt initiation
      of evidence-based treatments, investigation of alternative diagnoses for chest
      pain, or discharge, and permit better utilization of healthcare resources. A non
      trivial proportion of patients fall in an indeterminate category according to
      rule-out algorithms, and minimal evidence-based guidance exists for the optimal
      evaluation, monitoring, and treatment of these patients. The Cardiovascular Round
      Table of the ESC proposes approaches for the optimal application of early
      strategies in clinical practice to improve patient care following the review of
      recent advances in the early diagnosis of acute coronary syndrome. The following
      specific 'indeterminate' patient categories were considered: (i) patients with
      symptoms and high-sensitivity cardiac troponin <99th percentile; (ii) patients
      with symptoms and high-sensitivity troponin <99th percentile but above the limit
      of detection; (iii) patients with symptoms and high-sensitivity troponin >99th
      percentile but without dynamic change; and (iv) patients with symptoms and high
      sensitivity troponin >99th percentile and dynamic change but without coronary
      plaque rupture/erosion/dissection. Definitive evidence is currently lacking to
      manage these patients whose early diagnosis is 'indeterminate' and these areas of
      uncertainty should be assigned a high priority for research.

PMID- 29029111
TI  - Short-term and mid-term survival in bronchial sleeve resection by robotic system
      versus thoracotomy for centrally located lung cancer.
AB  - OBJECTIVES: The aim of this study was to compare the short-term and mid-term
      results of patients with centrally located lung cancer who underwent bronchial
      sleeve resection by robotic system or thoracotomy. METHODS: From September 2014
      to September 2015, 103 patients, including 17 robotic and 86 open cases, were
      included in our study. All the clinicopathological data, operative details and
      follow-up information were investigated. RESULTS: There were no intraoperative
      deaths. The mean console time was 113.59 min. The operative time for robotic
      surgery (155.06 +/- 44.75 min), even in our initial cases, was comparable to that
      for thoracotomy (150.30 +/- 47.84 min, P = 0.71). The 30-day mortality rate in
      the robotic and thoracotomy groups was 1 (6%) patient and 2 (2%) patients,
      respectively, with no significant difference (P = 0.43). A total of 4 (24%)
      patients in the robotic group and 22 (26%) patients in the thoracotomy group
      experienced postoperative complications (P = 0.86). In multivariable analysis,
      tumour size and postoperative radiotherapy were significant predictors of relapse
      free survival, whereas only the intensive care unit stay was a significant
      predictor of overall survival. There was no significant difference in relapse
      free survival (log-rank P = 0.16) and overall survival (log-rank P = 0.59)
      between the 2 groups. CONCLUSIONS: Robotic surgery for bronchial sleeve resection
      is safe and feasible and has similar oncological outcomes compared with open
      procedures. But long-term survival still needs to be investigated.

PMID- 29029112
TI  - Diversity and regulation of intrinsic beta-lactamases from non-fermenting and
      other Gram-negative opportunistic pathogens.
AB  - This review deeply addresses for the first time the diversity, regulation and
      mechanisms leading to mutational overexpression of intrinsic beta-lactamases from
      non-fermenting and other non-Enterobacteriaceae Gram-negative opportunistic
      pathogens. After a general overview of the intrinsic beta-lactamases described so
      far in these microorganisms, including circa. 60 species and 100 different
      enzymes, we review the wide array of regulatory pathways of these beta
      lactamases. They include diverse LysR-type regulators, which control the
      expression of beta-lactamases from relevant nosocomial pathogens such as
      Pseudomonas aeruginosa or Stenothrophomonas maltophilia or two-component
      regulators, with special relevance in Aeromonas spp., along with other pathways.
      Likewise, the multiple mutational mechanisms leading to beta-lactamase
      overexpression and beta-lactam resistance development, including AmpD (N-acetyl
      muramyl-L-alanine amidase), DacB (PBP4), MrcA (PPBP1A) and other PBPs, BlrAB (two
      component regulator) or several lytic transglycosylases among others, are also
      described. Moreover, we address the growing evidence of a major interplay between
      beta-lactamase regulation, peptidoglycan metabolism and virulence. Finally, we
      analyse recent works showing that blocking of peptidoglycan recycling (such as
      inhibition of NagZ or AmpG) might be useful to prevent and revert beta-lactam
      resistance. Altogether, the provided information and the identified gaps should
      be valuable for guiding future strategies for combating multidrug-resistant Gram
      negative pathogens.

PMID- 29029113
TI  - Estrogen Metabolism in Abdominal Subcutaneous and Visceral Adipose Tissue in
      Postmenopausal Women.
AB  - Context: In postmenopausal women, adipose tissue (AT) levels of estrogens exceed
      circulating concentrations. Although increased visceral AT after menopause is
      related to metabolic diseases, little is known about differences in estrogen
      metabolism between different AT depots. Objective: We compared concentrations of
      and metabolic pathways producing estrone and estradiol in abdominal subcutaneous
      and visceral AT in postmenopausal women. Design, Setting, Patients, and
      Interventions: AT and serum samples were obtained from 37 postmenopausal women
      undergoing surgery for nonmalignant gynecological reasons. Serum and AT estrone,
      estradiol, and serum estrone sulfate (E1S) concentrations were quantitated using
      liquid chromatography-tandem mass spectrometry. Activity of steroid sulfatase and
      reductive 17beta-hydroxysteroid dehydrogenase enzymes was measured using
      radiolabeled precursors. Messenger RNA (mRNA) expression of estrogen-converting
      enzymes was analyzed by real-time reverse transcription quantitative polymerase
      chain reaction. Results: Estrone concentration was higher in visceral than
      subcutaneous AT (median, 928 vs 706 pmol/kg; P = 0.002) and correlated positively
      with body mass index (r = 0.46; P = 0.011). Both AT depots hydrolyzed E1S to
      estrone, and visceral AT estrone and estradiol concentrations correlated
      positively with serum E1S. Compared with visceral AT, subcutaneous AT produced
      more estradiol from estrone (median rate of estradiol production, 1.02 vs 0.57
      nmol/kg AT/h; P = 0.004). In visceral AT, the conversion of estrone to estradiol
      increased with waist circumference (r = 0.65; P = 0.022), and estradiol
      concentration correlated positively with mRNA expression of HSD17B7 (r = 0.76; P
      = 0.005). Conclusions: Both estrone and estradiol production in visceral AT
      increased with adiposity, but estradiol was produced more effectively in
      subcutaneous fat. Both AT depots produced estrone from E1S. Increasing visceral
      adiposity could increase overall estrogen exposure in postmenopausal women.

PMID- 29029114
TI  - Carbapenem-resistant Citrobacter spp. isolated in Spain from 2013 to 2015
      produced a variety of carbapenemases including VIM-1, OXA-48, KPC-2, NDM-1 and
      VIM-2.
AB  - Objectives: There is little information about carbapenemase-producing (CP)
      Citrobacter spp. We studied the molecular epidemiology and microbiological
      features of CP Citrobacter spp. isolates collected in Spain (2013-15). Methods:
      In total, 119 isolates suspected of being CP by the EUCAST screening cut-off
      values were analysed. Carbapenemases and ESBLs were characterized using PCR and
      sequencing. The genetic relationship among Citrobacter freundii isolates was
      studied by PFGE. Results: Of the 119 isolates, 63 (52.9%) produced
      carbapenemases, of which 37 (58.7%) produced VIM-1, 20 (31.7%) produced OXA-48,
      12 (19%) produced KPC-2, 2 (3.2%) produced NDM-1 and 1 (1.6%) produced VIM-2; 9
      C. freundii isolates co-produced VIM-1 plus OXA-48. Fourteen isolates (22.2%)
      also carried ESBLs: 8 CTX-M-9 plus SHV-12, 2 CTX-M-9, 2 SHV-12 and 2 CTX-M-15.
      Fifty-seven isolates (90.5%) were C. freundii, 4 (6.3%) were Citrobacter koseri,
      1 (1.6%) was Citrobacter amalonaticus and 1 (1.6%) was Citrobacter braakii. By
      EUCAST breakpoints, eight (12.7%) of the CP isolates were susceptible to the four
      carbapenems tested. In the 53 CP C. freundii analysed by PFGE, a total of 44
      different band patterns were observed. Four PFGE clusters were identified:
      cluster 1 included eight isolates co-producing VIM-1 and OXA-48; blaVIM-1 was
      carried in a class 1 integron (intI-blaVIM-1-aacA4-dfrB1-aadA1-catB2
      qacEDelta1/sul1) and blaOXA-48 was carried in a Tn1999.2 transposon. Conclusions:
      We observed the clonal and polyclonal spread of CP Citrobacter spp. across
      several Spanish geographical areas. Four species of Citrobacter spp. produced up
      to five carbapenemase types, including co-production of VIM-1 plus OXA-48. Some
      CP Citrobacter spp. isolates were susceptible to the four carbapenems tested, a
      finding with potential clinical implications.

PMID- 29029115
TI  - Whole-Genome Next-Generation Sequencing to Study Within-Host Evolution of
      Norovirus (NoV) Among Immunocompromised Patients With Chronic NoV Infection.
AB  - Background: The genus Norovirus comprises large genetic diversity, and new GII.4
      variants emerge every 2-3 years. It is unknown in which host these new variants
      originate. Here we study whether prolonged shedders within the immunocompromised
      population could be a reservoir for newly emerging strains. Methods: Sixty-five
      fecal samples from 16 immunocompromised patients were retrospectively selected.
      Isolated viral RNA was enriched by hybridization with a custom norovirus whole
      genome RNA bait set and deep sequenced on the Illumina MiSeq platform. Results:
      Patients shed virus for average 352 days (range, 76-716 days). Phylogenetic
      analysis showed distinct GII.4 variants in 3 of 13 patients (23%). The viral
      mutation rates were variable between patients but did not differ between various
      immune status groups. All within-host GII.4 viral populations showed amino acid
      changes at blocking epitopes over time, and the majority of VP1 amino acid
      mutations were located at the capsid surface. Conclusions: This study found
      viruses in immunocompromised hosts that are genetically distinct from viruses
      circulating in the general population, and these patients therefore may contain a
      reservoir for newly emerging strains. Future studies need to determine whether
      these new strains are of risk to other immunocompromised patients and the general
      population.

PMID- 29029117
TI  - The European Registry for Patients with Mechanical Circulatory Support (EUROMACS)
      of the European Association for Cardio-Thoracic Surgery (EACTS): second report.
AB  - OBJECTIVES: The European Registry for Patients with Mechanical Circulatory
      Support (EUROMACS) was founded in Berlin, Germany. EUROMACS is supported fully by
      the European Association for Cardio-Thoracic Surgery (EACTS) and, since 2014, has
      functioned as a committee of the EACTS. The purpose of having the EUROMACS as a
      part of the EACTS is to accumulate clinical data related to long-term mechanical
      circulatory support for scientific purposes and to publish annual reports.
      METHODS: Participating hospitals contributed surgical and cardiological pre-,
      peri- and long-term postoperative data of mechanical circulatory support implants
      to the registry. Data for all implants performed from 1 January 2011 to 31
      December 2016 were analysed. Several auditing methods were used to monitor the
      quality of the data. Data could be provided for in-depth studies, and custom data
      could be provided at the request of clinicians and scientists. This report
      includes updates of patient characteristics, implant frequency, mortality rates
      and adverse events. RESULTS: Fifty-two hospitals participated in the registry.
      This report is based on 2947 registered implants in 2681 patients. Survival of
      adult patients (>17 years of age) with continuous-flow left ventricular assist
      devices with a mean follow-up of 391 days was 69% (95% confidence interval 66
      71%) 1 year after implantation. On average, patients were observed for 12 months
      (median 7 months, range 0-70 months). When we investigated for adverse events, we
      found an overall event rate per 100 patient-months of 3.56 for device
      malfunction, 6.45 for major bleeding, 6.18 for major infection and 3.03 for
      neurological events within the first 3 months after implantation. CONCLUSIONS:
      Compared to the first EUROMACS report, the number of participating hospitals
      increased from 21 to 52 (+148%), whereas the number of registered implants more
      than tripled from 825 to 2947 (+257%). The increase in the number of
      participating hospitals led us to increase the quality control measures through
      data input control, on-site audits and statistical analyses.

PMID- 29029118
TI  - Potential Side Effects of the Entomopathogenic Fungus Metarhizium anisopliae on
      the Egg Parasitoid Trichogramma pretiosum (Hymenoptera: Trichogrammatidae) Under
      Controlled Conditions.
AB  - The purpose was to evaluate the side effects of strains Metarhizium anisopliae
      (Metsch.) Sorokin sensu lato Unioeste 43 and M. anisopliae sensu stricto ESALQ
      1641 on Trichogramma pretiosum Riley (Hymenoptera: Trichogrammatidae) under
      controlled conditions. A free-choice test for parasitism was performed, with the
      confinement of T. pretiosum females mated with cards (1 * 5 cm) containing age
      standardized Anagasta kuehniella Zeller eggs, either sprayed with a fungal strain
      (109 conidia/ml) or 0.01% v/v Tween 80 (control). For the no-choice tests, T.
      pretiosum females mated were confined with cards sprayed with fungal strains
      before or after parasitism, and cards with fungal applications at different
      times. The number of parasitized eggs, percentage of emergence, longevity, egg-to
      adult period, sex ratio, total and confirmed mortality by the fungus, and
      longevity of females that parasitized previously sprayed eggs, were assessed.
      Histological analysis of immature phases was also performed. The fungus was
      repellent to T. pretiosum in the free-choice test, while in the no-choice test,
      fungal applications before and after parasitism did not affect the number of eggs
      parasitized by T. pretiosum or the sex ratio of emerging adults. However, both
      strains affected adult emergence rates, the egg-to-adult period, and longevity.
      Overall, both M. anisopliae strains had minor effects on these biological
      parameters of T. pretiosum under controlled conditions. Hyphae were not detected
      in histological observations of immature stages of the parasitoid.

PMID- 29029116
TI  - Upregulation of IRS1 Enhances IGF1 Response in Y537S and D538G ESR1 Mutant Breast
      Cancer Cells.
AB  - Increased evidence suggests that somatic mutations in the ligand-binding domain
      of estrogen receptor [ER (ERalpha/ESR1)] are critical mediators of endocrine
      resistant breast cancer progression. Insulinlike growth factor-1 (IGF1) is an
      essential regulator of breast development and tumorigenesis and also has a role
      in endocrine resistance. A recent study showed enhanced crosstalk between IGF1
      and ERalpha in ESR1 mutant cells, but detailed mechanisms are incompletely
      understood. Using genome-edited MCF-7 and T47D cell lines harboring Y537S and
      D538G ESR1 mutations, we characterized altered IGF1 signaling. RNA sequencing
      revealed upregulation of multiple genes in the IGF1 pathway, including insulin
      receptor substrate-1 (IRS1), consistent in both Y537S and D538G ESR1 mutant cell
      line models. Higher IRS1 expression was confirmed by quantitative reverse
      transcription polymerase chain reaction and immunoblotting. ESR1 mutant cells
      also showed increased levels of IGF-regulated genes, reflected by activation of
      an IGF signature. IGF1 showed increased sensitivity and potency in growth
      stimulation of ESR1 mutant cells. Analysis of downstream signaling revealed the
      phosphoinositide 3-kinase (PI3K)-Akt axis as a major pathway mediating the
      enhanced IGF1 response in ESR1 mutant cells. Decreasing IRS1 expression by small
      interfering RNA diminished the increased sensitivity to IGF1. Combination
      treatment with inhibitors against IGF1 receptor (IGF1R; OSI-906) and ER
      (fulvestrant) showed synergistic growth inhibition in ESR1 mutant cells,
      particularly at lower effective concentrations. Our study supports a critical
      role of enhanced IGF1 signaling in ESR1 mutant cell lines, pointing toward a
      potential for cotargeting IGF1R and ERalpha in endocrine-resistant breast tumors
      with mutant ESR1.

PMID- 29029119
TI  - The end of the unique myocardial band: Part II. Clinical and functional
      considerations.
AB  - Two of the leading concepts of mural ventricular architecture are the unique
      myocardial band and the myocardial mesh model. We have described, in an
      accompanying article published in this journal, how the anatomical, histological
      and high-resolution computed tomographic studies strongly favour the latter
      concept. We now extend the argument to describe the linkage between mural
      architecture and ventricular function in both health and disease. We show that
      clinical imaging by echocardiography and magnetic resonance imaging, and
      electrophysiological studies, all support the myocardial mesh model. We also
      provide evidence that the unique myocardial band model is not compatible with
      much of scientific research.

PMID- 29029120
TI  - Diagnostic Usefulness of Varicella-Zoster Virus Real-Time Polymerase Chain
      Reaction Analysis of DNA in Saliva and Plasma Specimens From Patients With Herpes
      Zoster.
AB  - Background: We evaluated the diagnostic usefulness of polymerase chain reaction
      (PCR) analysis for detecting varicella-zoster virus (VZV) infection and
      reactivation of VZV, using DNA extracted from saliva and plasma specimens
      obtained from subjects with suspected herpes zoster and from healthy volunteers
      during stressful and nonstressful conditions. Methods: There were 52 patients
      with a diagnosis of herpes zoster (group 1), 30 with a diagnosis of zoster
      mimicking disease (group 2), and 27 healthy volunteers (group 3). Saliva and
      plasma samples were evaluated for VZV DNA by real-time PCR analysis. Results:
      Among patients with suspected herpes zoster (ie, patients in groups 1 and 2), the
      sensitivity of PCR analysis of salivary DNA for detecting VZV (88%; 95%
      confidence interval [CI], 74%-95%) was significantly higher than that of PCR
      analysis of plasma DNA (28%; 95% CI, 16%-44%; P < .001), whereas the specificity
      of PCR analysis of salivary DNA (100%; 95% CI, 88%-100%) was similar to that of
      PCR analysis of plasma DNA (100%; 95% CI, 78%-100%; P > .99). VZV DNA was not
      detected in saliva and plasma samples from group 3 (0%; 95% CI, 0%-14%).
      Conclusions: Real-time PCR analysis of salivary DNA is more sensitive than that
      of plasma DNA for detecting VZV among patients with suspected herpes zoster. We
      found no subclinical reactivation of VZV in group 3 following exposure to common
      stressful conditions.

PMID- 29029121
TI  - Clinical Heterogeneity and Phenotypic Expansion of NaPi-IIa-Associated Disease.
AB  - Context: NaPi-IIa, encoded by SLC34A1, is a key phosphate transporter in the
      mammalian proximal tubule and plays a cardinal role in renal phosphate handling.
      NaPi-IIa impairment has been linked to various overlapping clinical syndromes,
      including hypophosphatemic nephrolithiasis with osteoporosis, renal Fanconi
      syndrome with chronic kidney disease, and, most recently, idiopathic infantile
      hypercalcemia and nephrocalcinosis. Objectives: We studied the molecular basis of
      idiopathic infantile hypercalcemia with partial proximal tubulopathy in two
      apparently unrelated patients of Israeli and Turkish descent. Design: Genetic
      analysis in two affected children and their close relatives was performed using
      whole-exome sequencing, followed by in vitro localization and trafficking
      analysis of mutant NaPi-IIa. Results: Mutation and haplotype analyses in both
      patients revealed a previously described homozygous loss-of-function inserted
      duplication (p.I154_V160dup) in NaPi-IIa, which is inherited identical-by-descent
      from a common ancestor. The shared mutation was originally reported by our team
      in two adult siblings with renal Fanconi syndrome, hypophosphatemic bone disease,
      and progressive renal failure who are family members of one of the infants
      reported herein. In vitro localization assays and biochemical analysis of
      p.I154_V160dup and of additional NaPi-IIa mutants harboring a trafficking defect
      indicate aberrant retention at the endoplasmic reticulum in an immature and
      underglycosylated state, leading to premature proteasomal degradation.
      Conclusions: Our findings expand the phenotypic spectrum of NaPi-IIa disruption,
      reinforce its link with proximal tubular impairment, enable longitudinal study of
      the natural history of the disease, and shed light on cellular pathways
      associated with loss of function and impaired trafficking of NaPi-IIa mutants.

PMID- 29029123
TI  - Outcome of elevated CA125 values from primary care following implementation of
      ovarian cancer guidelines.
AB  - Background: Ovarian cancer presents later in the UK compared to economically
      similar countries. National guidance suggests measuring CA125 in primary care as
      a means of bringing patients to specialist attention. Aim: To investigate the
      outcome of CA125 values measured in accordance with this policy. Setting and
      design: Examination of the laboratory records of female patients from the usual
      catchment population of one general hospital in whom CA125 was measured from
      primary care in a calendar year. Methods: Those with values >35 u/ml were
      identified. Electronic records within the hospital were interrogated to identify
      what further evaluation had been undertaken whether ovarian or primary peritoneal
      cancer had been diagnosed or what other pathology was identified. We also
      reviewed the CA125 measurement history of patients diagnosed over 3 years by any
      route. Results: One hundred and sixty-four new cases of CA125 >=35 u/ml were
      found. Further information was available for 152 of them. Sixteen had ovarian or
      primary peritoneal cancer and 16 had other cancers. In 50 no cause for the
      abnormality was found. The remainder had various non-malignant conditions. The
      specificity for carcinoma of ovary/primary peritoneal carcinoma was 95.4% [95%
      confidence interval: 94.8-96.0). In a 3-year period, 65 patients were diagnosed
      with ovarian or primary peritoneal cancer, 5 had values of CA125 between 20 and
      35 u/ml shortly before diagnosis. Conclusions: The CA125 level is a useful
      diagnostic test for ovarian cancer which has been embraced by primary care but
      higher sensitivity for earlier disease will require strategies to improve the
      specificity.

PMID- 29029124
TI  - Benzalkonium Chloride Provides Remarkable Stability to Liquid Protein Lures for
      Trapping Anastrepha obliqua (Diptera: Tephritidae).
AB  - Hydrolyzed protein lures are widely used to monitor fruit fly pests but are
      rapidly degraded by microbial activity and must be replaced frequently. To
      improve the stability of lures, the quaternary ammonium biocide, benzalkonium
      chloride (BC), was evaluated in mixtures with two hydrolyzed proteins commonly
      used to monitor Anastrepha spp. The mean number of Anastrepha obliqua adults
      captured during six consecutive weeks using Captor + borax with the addition of
      240 mg BC/liter, not renewed during the test, was similar to Captor + borax that
      was replaced at weekly intervals and was more effective than Captor + borax
      without BC. Numbers of A. obliqua flies captured in 30% CeraTrap diluted in water
      containing 240 mg BC/liter were similar to those caught in traps baited with
      Captor + borax or 30% CeraTrap without BC in the first 9 d of evaluation but was
      significantly more effective than both lures after 56 d. After >2 mo of use, 30%
      CeraTrap containing 240 mg BC/liter remained as effective as newly prepared 30%
      CeraTrap. The addition of BC to lures reduced surface tension of liquid lures by
      ~40-50%. However, when BC was increased to 720 mg BC/liter, only a small
      additional reduction in surface tension was observed and higher concentrations of
      BC did not increase capture rates. These findings could contribute to reduced
      costs for trapping networks and the development of long-lasting formulations of
      liquid protein lures for bait stations and mass-trapping targeted at major
      tephritid pests.

PMID- 29029122
TI  - Immunogenicity and Safety of the HZ/su Adjuvanted Herpes Zoster Subunit Vaccine
      in Adults Previously Vaccinated With a Live Attenuated Herpes Zoster Vaccine.
AB  - Background: Protection against herpes zoster (HZ) induced by the live attenuated
      zoster vaccine Zostavax (ZVL) wanes within 3-7 years. Revaccination may renew
      protection. We assessed whether (re)vaccination with the adjuvanted HZ subunit
      vaccine candidate (HZ/su) induced comparable immune responses in previous ZVL
      recipients and ZVL-naive individuals (HZ-NonVac). Methods: In an open-label,
      multicenter study, adults >=65 years of age, vaccinated with ZVL >=5 years
      previously (HZ-PreVac), were matched to ZVL-naive adults (HZ-NonVac).
      Participants received 2 doses of HZ/su 2 months apart. The primary objective of
      noninferiority of the humoral immune response 1 month post-dose 2 was considered
      demonstrated if the upper limit of the 95% confidence interval (CI) of the
      adjusted anti-glycoprotein E geometric mean concentration (GMC) ratio of HZ
      NonVac over HZ-PreVac was <1.5. HZ/su cellular immunogenicity, reactogenicity,
      and safety were also assessed. Results: In 430 participants, humoral immune
      response to HZ/su was noninferior in HZ-PreVac compared with HZ-NonVac (adjusted
      GMC ratio, 1.04 [95% CI, .92-1.17]). Cellular immunogenicity, reactogenicity, and
      safety appeared to be comparable between groups. HZ/su was well-tolerated, with
      no safety concerns raised within 1 month post-dose 2. Conclusions: HZ/su induces
      a strong immune response irrespective of prior vaccination with ZVL, and may be
      an attractive option to revaccinate prior ZVL recipients. Clinical Trials
      Registration: NCT02581410.

PMID- 29029125
TI  - Vaccine Prevention of Respiratory Syncytial Virus Infection in Older Adults: The
      Work Continues.

PMID- 29029126
TI  - Hyalomma dromedarii (Acari: Ixodidae) Salivary Gland Extract Inhibits
      Angiogenesis and Exhibits In Vitro Antitumor Effects.
AB  - Hard ticks (Acari: Ixodidae) are blood-sucking ectoparasites characterized by the
      extended period of their attachment to their host. To access their bloodmeal,
      ticks secrete saliva containing a range of molecules that target the host's
      inflammation, immune system, and hemostatic components. Some of these molecules
      reportedly possess antiangiogenic and antitumor properties. The present study
      describes our investigation, the first of its kind, of the antiangiogenic and
      antitumoral effects of the Hyalomma dromedarii Koch, 1844 (Acari: Ixodidae),
      salivary gland extract (SGE), which inhibited the adhesion and migration of Human
      Umbilical Vein Endothelial Cells (HUVECs) in a dose-dependent manner, as well as
      angiogenesis in the Chick Chorioallantoic Membrane model. Interestingly, H.
      dromedarii SGE exerted an antiproliferative effect on U87 glioblastoma cells and
      inhibited their adhesion and migration to fibrinogen. These results open up new
      possibilities for characterizing and developing new molecules involved in the key
      steps of tumor progression.

PMID- 29029129
TI  - A visual review of the human pathogen Streptococcus pneumoniae.
AB  - Being the principal causative agent of bacterial pneumonia, otitis media,
      meningitis and septicemia, the bacterium Streptococcus pneumoniae is a major
      global health problem. To highlight the molecular basis of this problem, we have
      portrayed essential biological processes of the pneumococcal life cycle in eight
      watercolor paintings. The paintings are done to a consistent nanometer scale
      based on currently available data from structural biology and proteomics. In this
      review article, the paintings are used to provide a visual review of protein
      synthesis, carbohydrate metabolism, cell wall synthesis, cell division, teichoic
      acid synthesis, virulence, transformation and pilus synthesis based on the
      available scientific literature within the field of pneumococcal biology.
      Visualization of the molecular details of these processes reveals several
      scientific questions about how molecular components of the pneumococcal cell are
      organized to allow biological function to take place. By the presentation of this
      visual review, we intend to stimulate scientific discussion, aid in the
      generation of scientific hypotheses and increase public awareness. A narrated
      video describing the biological processes in the context of a whole-cell
      illustration accompany this article.

PMID- 29029127
TI  - Antibody Kinetics and Response to Routine Vaccinations in Infants Born to Women
      Who Received an Investigational Trivalent Group B Streptococcus Polysaccharide
      CRM197-Conjugate Vaccine During Pregnancy.
AB  - Background: Maternal vaccination against group B Streptococcus (GBS) might
      provide protection against invasive GBS disease in infants. We investigated the
      kinetics of transplacentally transferred GBS serotype-specific capsular
      antibodies in the infants and their immune response to diphtheria toxoid and
      pneumococcal vaccination. Methods: This phase 1b/2, observer-blind, single-center
      study (NCT01193920) enrolled infants born to women previously randomized
      (1:1:1:1) to receive either GBS vaccine at dosages of 0.5, 2.5, or 5.0 MUg of
      each of 3 CRM197-glycoconjugates (serotypes Ia, Ib, and III), or placebo. Infants
      received routine immunization: combination diphtheria vaccine (diphtheria-tetanus
      acellular pertussis-inactivated poliovirus/Haemophilus influenzae type b vaccine;
      age 6/10/ 14 weeks) and 13-valent pneumococcal CRM197-conjugate vaccine (PCV13;
      age 6/14 weeks and 9 months). Antibody levels were assessed at birth, day (D) 43,
      and D91 for GBS serotypes; 1 month postdose 3 (D127) for diphtheria; and 1 month
      postprimary (D127) and postbooster (D301) doses for pneumococcal serotypes.
      Results: Of 317 infants enrolled, 295 completed the study. In infants of GBS
      vaccine recipients, GBS serotype-specific antibody geometric mean concentrations
      were significantly higher than in the placebo group at all timepoints and
      predictably decreased to 41%-61% and 26%-76% of birth levels by D43 and D91,
      respectively. Across all groups, >=95% of infants were seroprotected against
      diphtheria at D127 and >=91% of infants had seroprotective antibody levels
      against each PCV13 pneumococcal serotype at D301. Conclusions: Maternal
      vaccination with an investigational CRM197-glycoconjugate GBS vaccine elicited
      higher GBS serotype-specific antibody levels in infants until 90 days of age,
      compared with a placebo group, and did not affect infant immune responses to
      diphtheria toxoid and pneumococcal vaccination. Clinical Trials Registration:
      NCT01193920.

PMID- 29029128
TI  - Evolution and Spatiotemporal Dynamics of Enterovirus A71 Subgenogroups in
      Vietnam.
AB  - Background: Enterovirus A71 (EV-A71) is the major cause of severe hand, foot, and
      mouth disease and viral encephalitis in children across the Asia-Pacific region,
      including in Vietnam, which has experienced a high burden of disease in recent
      years. Multiple subgenogroups (C1, C4, C5, and B5) concurrently circulate in the
      region with a large variation in epidemic severity. The relative differences in
      their evolution and epidemiology were examined within Vietnam and globally.
      Methods: A total of 752 VP1 gene sequences were analyzed (413 generated in this
      study combined with 339 obtained from GenBank), collected from patients in 36
      provinces in Vietnam during 2003-2013, along with epidemiological metadata.
      Globally representative VP1 gene datasets of subgenogroups were used to
      coestimate time-resolved phylogenies and relative genetic diversity to infer
      virus origins and regional transmission network. Results: Despite frequent virus
      migration between countries, the highest genetic diversity of individual
      subgenogroups was maintained independently for several years in specific Asian
      countries representing genogroup-specific sources of EV-A71 diversity.
      Conclusion: This study highlights a persistent transmission network of EV-A71,
      with specific Asian countries seeding other countries in the region and beyond,
      emphasizing the need for improved EV-A71 surveillance and detailed genetic and
      antigenic characterization.

PMID- 29029130
TI  - Alternative Sample Types for HIV-1 Antiretroviral Drug Resistance Testing.
AB  - Monitoring human immunodeficiency virus type 1 (HIV-1) drug resistance is
      critical for assessing ART effectiveness and treatment outcomes for HIV-1
      infected individuals, including children, worldwide. Traditionally, testing for
      HIV-1 drug resistance has primarily been performed on plasma samples, and with
      commercially available, clinically validated assays that are costly and difficult
      to access. While plasma is the preferred sample for HIV-1 drug resistance
      genotyping, plasma analysis requires sophisticated laboratory equipment,
      personnel, space, and stringent storage conditions for maintenance of sample
      integrity and transport. With the limitations in feasibility and affordability of
      providing these ideal conditions for plasma genotyping in resource-constrained
      settings, the field has gained substantial experience with the dried blood spot
      (DBS) technique as an alternative. Moreover, DBS analysis can be used to
      comprehensively monitor the spread of the epidemic with applications to more
      sensitive and quantitative technologies to assess HIV-1 globally.

PMID- 29029132
TI  - General practitioners' strategies in consultations with immigrants in Norway
      practice-based shared reflections among participants in focus groups.
AB  - Background: Immigrants comprise 16.8% of the population in Norway and meet
      General Practitioners (GPs) as their first point of contact with most health care
      services as do others in Norway. While Norwegian GPs are not trained in cultural
      competence, little is known about the extent to which they see good care for
      immigrants as relying on specific strategies. Objectives: To explore the thoughts
      of GPs in Norway about strategies they might use with immigrant patients.
      Methods: We performed focus groups posing the question 'What strategies do you
      use when meeting immigrant patients?' to three groups of GPs working in Norway.
      Two groups comprised 10 trainee GPs each; the final group comprised eight
      certified GPs. Verbatim transcripts were analysed by systematic text
      condensation. Results: Strategies for consultations with immigrants emerged
      gradually throughout the focus groups, coalescing around (i) Respect and learn
      about immigrant culture. (ii) Particularize diagnosis and care, accommodating
      epidemiological and cultural knowledge for a given group, while keeping a keen
      eye on the individual. (iii) Inform about Norwegian health care. (iv) Organize
      resources such as time, translators and interdisciplinary teams. Other core
      elements of cultural competence, including reflections on the GP's own cultural
      background, were conspicuously absent, however. Conclusion: Given the growing
      numbers of immigrants and the early transfer of refugees to general practice, our
      study points to the urgent need of supplementing teaching in patient-centred
      clinical method with cultural competence. Our study also highlights the potential
      of educational GP groups to develop strategies for cross-cultural consultations.

PMID- 29029131
TI  - Plasma Amino Acids Stimulate Uncoupled Respiration of Muscle Subsarcolemmal
      Mitochondria in Lean but Not Obese Humans.
AB  - Context: Obesity is associated with mitochondrial dysfunction in skeletal muscle.
      Increasing the plasma amino acid (AA) concentrations stimulates mitochondrial
      adenosine triphosphate (ATP) production in lean individuals. Objective: To
      determine whether acute elevation in plasma AAs enhances muscle mitochondrial
      respiration and ATP production in subsarcolemmal (SS) and intermyofibrillar (IMF)
      mitochondria in obese adults. Design: Assessment of SS and IMF mitochondrial
      function during saline (i.e., control) and AA infusions. Participants: Eligible
      participants were healthy lean (body mass index, <25 kg/m2; age, 37 +/- 3 years;
      n = 10) and obese (body mass index >30 kg/m2; age 35 +/- 3 years; n = 11)
      subjects. Intervention: Single trial of saline infusion followed by AA infusion.
      SS and IMF mitochondria were isolated from muscle biopsies collected at the end
      of the saline and AA infusions. Main Outcomes: Mitochondrial respiration and ATP
      production. Results: AA infusion increased adenosine 5'-diphosphate (ADP)
      stimulated respiration and ATP production rates of SS mitochondria in the lean (P
      < 0.05), but not obese, subjects. Furthermore, AA infusion increased the
      uncoupled (i.e., non-ADP-stimulated) respiration of SS mitochondria in the lean
      subjects only (P < 0.05). AA infusion had no effect on any of these parameters in
      IMF mitochondria in either lean or obese subjects (P > 0.05). Conclusions:
      Increasing the plasma AA concentrations enhances the capacity for respiration and
      ATP production of muscle SS, but not IMF, mitochondria in lean individuals, in
      parallel with increases in uncoupled respiration. However, neither of these
      parameters increases in muscle SS or IMF mitochondria in obese individuals.

PMID- 29029133
TI  - Rapid Determination of Ebolavirus Infectivity in Clinical Samples Using a Novel
      Reporter Cell Line.
AB  - Modern ebolavirus diagnostics rely primarily on quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR), a sensitive method to detect
      viral genetic material in the acute phase of the disease. However, qRT-PCR does
      not confirm presence of infectious virus, presenting limitations in patient and
      outbreak management. Attempts to isolate infectious virus rely on in vivo or
      basic cell culture approaches, which prohibit rapid results and screening. In
      this study, we present a novel reporter cell line capable of detecting live
      ebolaviruses. These cells permit sensitive, large-scale screening and titration
      of infectious virus in experimental and clinical samples, independent of
      ebolavirus species and variant.

PMID- 29029135
TI  - Small increase in dolutegravir trough, but equivalent total dolutegravir exposure
      with simeprevir in HIV/HCV seronegative volunteers.
AB  - Background: Dolutegravir, an HIV integrase strand-transfer inhibitor, and
      simeprevir, an HCV NS3/4A PI, have the potential to interact as dolutegravir is a
      P-glycoprotein, uridine glucuronosyl transferase 1A1 and cytochrome P4503A
      substrate and simeprevir has been shown to mildly inhibit these. Objectives: To
      compare dolutegravir and simeprevir pharmacokinetics (PK) when given separately
      versus in combination. Methods: Healthy volunteers received: (i) 150 mg of
      simeprevir once daily for 7 days; (ii) 50 mg of dolutegravir once daily for 7
      days; and (iii) 150 mg of simeprevir once daily plus 50 mg of dolutegravir once
      daily for 7 days, with randomization to treatment sequence. Twenty-four hour
      intensive PK sampling was performed on day 7 of each sequence following observed
      dosing and a standardized meal. PK parameters were determined using non
      compartmental methods and compared using paired t-tests. Bioequivalence for area
      under the curve (AUCtau) and maximum concentration (Cmax) were also assessed.
      NCT02404805. Results: Twenty-four subjects completed all three sequences.
      Dolutegravir trough was increased 24% (P = 0.0003) with simeprevir. Dolutegravir
      AUCtau was increased 15% (P = 0.002), but was deemed bioequivalent as the 90% CI
      for the geometric mean ratio was 107%-123%. Dolutegravir Cmax was bioequivalent.
      Simeprevir PK was unaffected by dolutegravir. There were no discontinuations due
      to adverse events and all adverse events were mild to moderate in severity.
      Conclusions: Dolutegravir trough was increased slightly with simeprevir, but
      AUCtau was bioequivalent. Despite the increase in trough, dolutegravir
      concentrations were well within the range with established safety data.
      Suggesting that simeprevir and dolutegravir can be safely co-administered.

PMID- 29029134
TI  - The natural history and surgical outcome of patients with scimitar syndrome: a
      multi-centre European study.
AB  - Aims: Treatment decisions in patients with scimitar syndrome (SS) are often
      challenging, especially in patients with isolated SS who are often asymptomatic
      and who might be diagnosed accidentally. We queried a large multi-institutional
      registry of SS patients to evaluate the natural history of this condition and to
      determine the efficacy of surgical treatment in terms of survival and clinical
      status. Methods and results: We collected data on 485 SS patients from 51
      institutions; 279 (57%) patients were treated surgically (STPs) and 206 (43%)
      were clinically monitored (CMPs). Median age at last follow-up was 11.6 years
      (interquartile range 4-22 years). Overall survival probability at 30 years of age
      was 88% [85-92% confidence intervals (CI)] and was lower in patients with
      associated congenital heart disease (CHD) (P < 0.001) and pulmonary hypertension
      (P < 0.001). Most patients were asymptomatic at last follow-up (279/451, 62%);
      STPs were more frequently asymptomatic than CMPs (73% vs. 47%, P < 0.001), with
      fewer cardiac [odds ratio (OR) 0.42, 95% CI 0.22-0.82] and respiratory symptoms
      (OR 0.08, 95% CI 0.02-0.28). Many STPs (63/254, 25%) had stenosis/occlusion of
      the scimitar drainage, and this was associated with a younger age at surgery (OR
      0.4, CI 0.21-0.78). Conclusion: Patients with SS have a high overall survival.
      Survival probability was lower in patients with associated CHDs and in patients
      with pulmonary hypertension. Surgical treatment of SS is beneficial in reducing
      symptoms, however, given the significant risk of post-operative scimitar drainage
      stenosis/occlusion, it should be tailored to a comprehensive haemodynamic
      evaluation and to the patient's age.

PMID- 29029136
TI  - Susceptibility of Culex quinquefasciatus (Diptera: Culicidae) in Southern
      Louisiana to Larval Insecticides.
AB  - Mosquito control districts conduct rigorous insecticide treatments against both
      larval and adult Culex quinquefasciatus Say (Diptera: Culicidae), the primary
      vector of West Nile virus in the southern United States. However, the development
      of resistant populations of Cx. quinquefasciatus in response to extensive
      larvicide or adulticide applications has been demonstrated repeatedly across the
      world. Examining changes in insecticide susceptibility in treated field areas can
      help inform mosquito control districts as to whether or not their treatments
      remain effective. We hypothesized that frequent insecticide applications for the
      control of mosquitoes in East Baton Rouge Parish, Louisiana, lowered
      susceptibility of wild Cx. quinquefasciatus to larvicides. Larvicide
      susceptibility was measured using Lysinibacillus sphaericus, spinosad, and
      temephos in populations of Cx. quinquefasciatus sampled from sites in three
      Parishes where frequencies of insecticide applications varied, and frequencies of
      resistance were measured relative to a susceptible reference colony.
      Susceptibility to these larvicides was widespread, although fourfold resistance
      to the organophosphate temephos was detected at one site in East Baton Rouge
      Parish in the spring of 2016, which increased to eightfold resistance by the end
      of the mosquito season. Activities of esterases were found to be elevated in
      wild, temephos-resistant mosquitoes, indicating the potential role of these
      enzymes as a mechanism of resistance. The results of this study provide a
      baseline of comparison for future measurements of susceptibility in Cx.
      quinquefasciatus in Louisiana, and may help inform local mosquito control
      districts as to the effectiveness and sustainability of their insecticide
      programs.

PMID- 29029139
TI  - Quantitative deformation analysis differentiates ischaemic and non-ischaemic
      cardiomyopathy: sub-group analysis of the VINDICATE trial.
AB  - Aims: To test the hypothesis that patients with ischaemic cardiomyopathy (ICM)
      and non-ischaemic cardiomyopathy (NICM) have different torsion and strain
      parameters, and compare to healthy, age-matched controls. VINDICATE investigated
      efficacy of high-dose vitamin D on patients with heart failure (HF) secondary to
      left ventricular (LV) systolic dysfunction of any aetiology. It is important to
      differentiate ICM and NICM as treatment and prognosis varies significantly.
      Cardiovascular magnetic resonance (CMR) reliably determines aetiology of HF and
      tissue tagging techniques are recognized as the reference standard measures of
      strain and torsion. Methods and results: Fifty three patients (31 ICM, 22 NICM)
      from VINDICATE and 25 controls underwent CMR at 3.0T, including cine imaging in
      multiple planes and tissue tagging by spatial modulation of magnetization. CMR
      data were analysed blinded, by quantitatively reporting circumferential strain
      and torsion from tagged images and global longitudinal strain from feature
      tracking. HF patients had larger ventricles indexed to body surface area, lower
      left ventricular ejection fraction (LVEF), LV torsion, twist, and strain
      parameters compared to controls. There were no significant differences between
      ICM and NICM in age, blood pressure, heart rhythm, or NYHA status. There was no
      significant difference in LV dimensions, EF, and strain parameters between ICM
      and NICM. NICM patients had significantly lower LV twist (6.0 +/- 3.7 degrees 
      vs. 8.8 +/- 4.3 degrees , P = 0.023) and torsion (5.9 +/- 3.5 degrees  vs. 8.8 +/
      4.7 degrees , P = 0.017) compared to ICM. Conclusion: Twist, torsion, and strain
      are reduced in HF patients compared to controls. Torsion and twist are
      significantly lower in patients with NICM compared to ICM, despite similar
      volumetric dimensions, circumferential and longitudinal strain parameters, and
      LVEF.

PMID- 29029141
TI  - Targeted antiplatelet therapy: novel treatment options for ischaemic heart
      disease.

PMID- 29029137
TI  - Comparison of Thaumarchaeotal populations from four deep sea basins.
AB  - The nitrogen cycle in the marine environment is strongly affected by ammonia
      oxidizing Thaumarchaeota. In some marine settings, Thaumarchaeotes can comprise a
      large percentage of the prokaryotic population. To better understand the
      biogeographic patterns of Thaumarchaeotes, we sought to investigate differences
      in their abundance and phylogenetic diversity between geographically distinct
      basins. Samples were collected from four marine basins (The Caspian Sea, the
      Great Australian Bight, and the Central and Eastern Mediterranean). The
      concentration of bacterial and archaeal 16S rRNA genes and archaeal amoA genes
      were assessed using qPCR. Minimum entropy decomposition was used to elucidate the
      fine-scale diversity of Thaumarchaeotes. We demonstrated that there were
      significant differences in the abundance and diversity of Thaumarchaeotes between
      these four basins. The diversity of Thaumarchaeotal oligotypes differed between
      basins with many oligotypes only present in one of the four basins, which
      suggests that their distribution showed biogeographic patterning. There were also
      significant differences in Thaumarchaeotal community structure between these
      basins. This would suggest that geographically distant, yet geochemically similar
      basins may house distinct Thaumarchaeaotal populations. These findings suggest
      that Thaumarchaeota are very diverse and that biogeography in part contributes in
      determining the diversity and distribution of Thaumarchaeotes.

PMID- 29029140
TI  - Structural valve deterioration in the Mitroflow biological heart valve
      prosthesis.
AB  - OBJECTIVES: Concern has been raised regarding the long-term durability of the
      Mitroflow biological heart valve prosthesis. Our aim was to assess the incidence
      of structural valve degeneration (SVD) for the Mitroflow bioprosthesis in a
      nationwide study in Denmark including all patients alive in Denmark who had
      received a Mitroflow aortic bioprosthesis since 2000. METHODS: Patients alive in
      Denmark with a Mitroflow bioprosthesis implanted since January 2000 were invited
      to participate in a nationwide cross-sectional study with a predefined definition
      of SVD. Of 1552 patients, 861 patients had died and 47 patients had been
      reoperated with 40 reoperations due to SVD. The remaining 644 patients were
      invited for evaluation; 574 patients accepted and were evaluated for SVD. The
      incidence of SVD was calculated using competing risk regression analysis with
      death as the competing event. RESULTS: A total of 173 patients were diagnosed
      with SVD by echocardiography. Of these, 64 (11%) patients had severe SVD and 109
      (19%) patients moderate SVD. Severe SVD was associated with the age of the
      prosthesis and small prosthesis size [Size 21: hazard ratio (95% confidence
      interval, CI) 2.72 (0.97-8.56), P = 0.06; Size 19: 6.26 (1.63-24.06), P = 0.008].
      The cumulative incidences of reoperation or severe SVD at Year 9 were 12.5% for
      Size 19, 7.6% for Size 21 and 3.1 (1.2-6.4)% for Size 23. Median survival in
      patients with prosthesis Sizes 23-29 was 6.4 (95% CI 5.7-7.0) years, with Size 21
      it was 6.5 (95% CI 5.9-7.1) years and with Size 19 it was 6.9 (95% CI 5.7-8.2)
      years (P = 0.78). CONCLUSIONS: The incidence of undetected severe SVD was as high
      as the incidence of operated SVD. The overall risk for SVD is high for the
      Mitroflow bioprosthesis, especially if the prosthesis is small and older than 5
      years.

PMID- 29029142
TI  - Detecting myocardial infarction type 2: targetting the right patients.

PMID- 29029138
TI  - The Female Genital Tract Microbiome Is Associated With Vaginal Antiretroviral
      Drug Concentrations in Human Immunodeficiency Virus-Infected Women on
      Antiretroviral Therapy.
AB  - Background: The female genital tract (FGT) microbiome may affect vaginal pH and
      other factors that influence drug movement into the vagina. We examined the
      relationship between the microbiome and antiretroviral concentrations in the FGT.
      Methods: Over one menstrual cycle, 20 human immunodeficiency virus (HIV)-infected
      women virologically suppressed on tenofovir (TFV) disoproxil
      fumarate/emtricitabine and ritonavir-boosted atazanavir (ATV) underwent serial
      paired cervicovaginal and plasma sampling for antiretroviral concentrations using
      high-performance liquid chromatography-tandem mass spectrometry. Analysis of 16S
      ribosomal RNA gene sequencing of cervicovaginal lavage clustered each participant
      visit into a unique microbiome community type (mCT). Results: Participants were
      predominantly African American (95%), with a median age of 38 years.
      Cervicovaginal lavage sequencing (n = 109) resulted in a low-diversity mCT
      dominated by Lactobacillus (n = 40), and intermediate-diversity (n = 28) and high
      diversity (n = 41) mCTs with abundance of anaerobic taxa. In multivariable
      models, geometric mean FGT:plasma ratios varied significantly by mCT for all 3
      drugs. For both ATV and TFV, FGT:plasma was significantly lower in participant
      visits with high- and low-diversity mCT groups (all P < .02). For emtricitabine,
      FGT:plasma was significantly lower in participant visits with low- vs
      intermediate-diversity mCT groups (P = .002). Conclusions: Certain FGT mCTs are
      associated with decreased FGT antiretroviral concentrations. These findings are
      relevant for optimizing antiretrovirals used for biomedical HIV prevention in
      women.

PMID- 29029143
TI  - Genome-Wide Analysis of Genetic Risk Factors for Rheumatic Heart Disease in
      Aboriginal Australians Provides Support for Pathogenic Molecular Mimicry.
AB  - Background: Rheumatic heart disease (RHD) after group A streptococcus (GAS)
      infections is heritable and prevalent in Indigenous populations. Molecular
      mimicry between human and GAS proteins triggers proinflammatory cardiac valve
      reactive T cells. Methods: Genome-wide genetic analysis was undertaken in 1263
      Aboriginal Australians (398 RHD cases; 865 controls). Single-nucleotide
      polymorphisms were genotyped using Illumina HumanCoreExome BeadChips. Direct
      typing and imputation was used to fine-map the human leukocyte antigen (HLA)
      region. Epitope binding affinities were mapped for human cross-reactive GAS
      proteins, including M5 and M6. Results: The strongest genetic association was
      intronic to HLA-DQA1 (rs9272622; P = 1.86 * 10-7). Conditional analyses showed
      rs9272622 and/or DQA1*AA16 account for the HLA signal. HLA-DQA1*0101_DQB1*0503
      (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.09-1.90; P = 9.56 * 10-3)
      and HLA-DQA1*0103_DQB1*0601 (OR, 1.27; 95% CI, 1.07-1.52; P = 7.15 * 10-3) were
      risk haplotypes; HLA_DQA1*0301-DQB1*0402 (OR 0.30, 95%CI 0.14-0.65, P = 2.36 * 10
      3) was protective. Human myosin cross-reactive N-terminal and B repeat epitopes
      of GAS M5/M6 bind with higher affinity to DQA1/DQB1 alpha/beta dimers for the 2
      risk haplotypes than the protective haplotype. Conclusions: Variation at HLA_DQA1
      DQB1 is the major genetic risk factor for RHD in Aboriginal Australians studied
      here. Cross-reactive epitopes bind with higher affinity to alpha/beta dimers
      formed by risk haplotypes, supporting molecular mimicry as the key mechanism of
      RHD pathogenesis.

PMID- 29029145
TI  - Blood Meal Source Characterization Using Illumina Sequencing in the Chagas
      Disease Vector Rhodnius pallescens (Hemiptera: Reduviidae) in Panama.
AB  - Accurate blood meal identification is critical to understand hematophagous vector
      host relationships. This study describes a customizable Next-Generation
      Sequencing (NGS) approach to identify blood meals from Rhodnius pallescens
      (Hemiptera: Reduviidae) triatomines using multiple barcoded primers and existing
      software to pick operational taxonomic units and match sequences for blood meal
      identification. We precisely identified all positive control samples using this
      method and further examined 74 wild-caught R. pallescens samples. With this novel
      blood meal identification method, we detected 13 vertebrate species in the blood
      meals, as well as single and multiple blood meals in individual bugs. Our results
      demonstrate the reliability and descriptive uses of our method.

PMID- 29029146
TI  - A Real-Time PCR Assay for the Separation of Autographa gamma (Noctuidae:
      Plusiinae) From Morphologically Similar Species in North America.
AB  - The silver Y moth, Autographa gamma L. (Noctuidae: Plusiinae), is a pest of major
      economic importance in its native range of Europe, Asia, and North Africa.
      Although not present in North America, larvae of A. gamma are commonly
      intercepted in commodity shipments at U.S. ports, and adult surveys are conducted
      each year in more than 20 states. Because of the similarity of A. gamma to
      several native North American species that are attracted to the same pheromone
      lure, morphological identification of adults is difficult and requires
      dissection. In 2010, a specimen of Autographa californica (Speyer, 1875)
      (Lepidoptera: Noctuidae) from Pennsylvania was incorrectly identified as A.
      gamma, signaling the need for an alternative method of rapid identification. Here
      we detail a real-time PCR assay capable of identifying A. gamma specimens in
      approximately 45 min using extracted DNA. The assay uses a hydrolysis probe that
      targets a species-specific segment of the CO1 DNA barcode region, while a control
      probe targets a conserved region of 18S rDNA. The assay was tested with two
      independent runs of 452 specimens of Plusiinae representing 23 different species.
      The assay provided unambiguous data 99.7% of the time and did not result in any
      false positives; these data were used to develop a rule set for interpreting the
      real-time PCR results. In addition, the same diagnostic probe was tested in bulk
      sample simulations using real-time PCR and droplet digital PCR where A. gamma
      could be detected in concentrations as low as 1:1,000,000 (gamma:californica).
      These experiments provide baseline data for developing a bulk sample assay.

PMID- 29029147
TI  - Maternal and Fetal Outcomes Among Pregnant Women With Human Monkeypox Infection
      in the Democratic Republic of Congo.
AB  - Human monkeypox is an endemic disease in rain-forested regions of central
      Democratic Republic of Congo. We report fetal outcomes for 1 of 4 pregnant women
      who participated in an observational study at the General Hospital of Kole
      (Sankuru Province), where 222 symptomatic subjects were followed between 2007 and
      2011. Of the 4 pregnant women, 1 gave birth to a healthy infant, 2 had
      miscarriages in the first trimester, and 1 had fetal death, with the macerated
      stillborn showing diffuse cutaneous maculopapillary skin lesions involving the
      head, trunk and extremities, including palms of hands and soles of feet.

PMID- 29029144
TI  - Broad-range survey of vector-borne pathogens and tick host identification of
      Ixodes ricinus from Southern Czech Republic.
AB  - Ixodes ricinus ticks are vectors of numerous human and animal pathogens. They are
      host generalists able to feed on more than 300 vertebrate species. The prevalence
      of tick-borne pathogens is influenced by host-vector-pathogen interactions that
      results in spatial distribution of infection risk. Broad-range polymerase chain
      reaction electrospray ionization mass spectrometry (PCR/ESI-MS) was used to
      analyze 435 I. ricinus nymphs from four localities in the south of the Czech
      Republic for the species identification of tick-borne pathogens. Borrelia
      burgdorferi sensu lato spirochetes were the most common pathogen detected in the
      ticks; 21% of ticks were positive for a single genospecies and 2% were co
      infected with two genospecies. Other tick-borne pathogens detected included
      Rickettsia helvetica (3.9%), R. monacensis (0.2%), Anaplasma phagocytophilum
      (2.8%), Babesia venatorum (0.9%), and Ba. microti (0.5%). The vertebrate host of
      the ticks was determined using PCR followed by reverse line blot hybridization
      from the tick's blood-meal remnants. The host was identified for 61% of ticks.
      DNA of two hosts was detected in 16% of samples with successful host
      identification. The majority of ticks had fed on artiodactyls (50.7%) followed by
      rodents (28.6%) and birds (7.8%). Other host species were wild boar, deer,
      squirrels, field mice and voles.

PMID- 29029148
TI  - The Crux of Ebola Diagnostics.

PMID- 29029149
TI  - No Clinical Benefit of Empirical Antimicrobial Therapy for Pediatric Diarrhea in
      a High-Usage, High-Resistance Setting.
AB  - Background: Pediatric diarrheal disease presents a major public health burden in
      low- to middle-income countries. The clinical benefits of empirical antimicrobial
      treatment for diarrhea are unclear in settings that lack reliable diagnostics and
      have high antimicrobial resistance (AMR). Methods: We conducted a prospective
      multicenter cross-sectional study of pediatric patients hospitalized with
      diarrhea containing blood and/or mucus in Ho Chi Minh City, Vietnam. Clinical
      parameters, including disease outcome and treatment, were measured. Shigella,
      nontyphoidal Salmonella (NTS), and Campylobacter were isolated from fecal
      samples, and their antimicrobial susceptibility profiles were determined.
      Statistical analyses, comprising log-rank tests and accelerated failure time
      models, were performed to assess the effect of antimicrobials on disease outcome.
      Results: Among 3166 recruited participants (median age 10 months; interquartile
      range, 6.5-16.7 months), one-third (1096 of 3166) had bloody diarrhea, and 25%
      (793 of 3166) were culture positive for Shigella, NTS, or Campylobacter. More
      than 85% of patients (2697 of 3166) were treated with antimicrobials;
      fluoroquinolones were the most commonly administered antimicrobials. AMR was
      highly prevalent among the isolated bacteria, including resistance against
      fluoroquinolones and third-generation cephalosporins. Antimicrobial treatment and
      multidrug resistance status of the infecting pathogens were found to have no
      significant effect on outcome. Antimicrobial treatment was significantly
      associated with an increase in the duration of hospitalization with particular
      groups of diarrheal diseases. Conclusions: In a setting with high antimicrobial
      usage and high AMR, our results imply a lack of clinical benefit for treating
      diarrhea with antimicrobials; adequately powered randomized controlled trials are
      required to assess the role of antimicrobials for diarrhea.

PMID- 29029151
TI  - Combined Toxicity of Three Essential Oils Against Aedes aegypti (Diptera:
      Culicidae) Larvae.
AB  - Essential oils are potential alternatives to synthetic insecticides because they
      have low mammalian toxicity, degrade rapidly in the environment, and possess
      complex mixtures of bioactive constituents with multi-modal activity against the
      target insect populations. Twenty-one essential oils were initially screened for
      their toxicity against Aedes aegypti (L.) larvae and three out of the seven most
      toxic essential oils (Manuka, oregano, and clove bud essential oils) were
      examined for their chemical composition and combined toxicity against Ae. aegypti
      larvae. Manuka essential oil interacted synergistically with oregano essential
      oil and antagonistically with clove bud essential oil. GC-MS analysis revealed
      the presence of 21 components in Manuka essential oil and three components each
      in oregano and clove bud essential oils. Eugenol (84.9%) and eugenol acetate
      (9.6%) were the principal constituents in clove bud essential oil while carvacrol
      (75.8%) and m-isopropyltoluene (15.5%) were the major constituents in oregano
      essential oil. The major constituents in Manuka essential oil were calamenene
      (20%) and 3-dodecyl-furandione (11.4%). Manuka essential oil interacted
      synergistically with eugenol acetate and antagonistically with eugenol,
      suggesting that eugenol was a major contributor to the antagonistic interaction
      between Manuka and clove bud essential oils. In addition, Manuka interacted
      synergistically with carvacrol suggesting its contribution to the synergistic
      interaction between Manuka and oregano essential oils. These findings provide
      novel insights that can be used to develop new and safer alternatives to
      synthetic insecticides.

PMID- 29029150
TI  - Antibiotic Use and New-Onset Inflammatory Bowel Disease in Olmsted County,
      Minnesota: A Population-Based Case-Control Study.
AB  - Background and Aims: Several studies have suggested significant associations
      between environmental factors and the risk of developing inflammatory bowel
      disease [IBD]. However, data supporting the role of antibiotics are conflicting.
      The aim of this study was to evaluate the association between antibiotic use and
      new-onset IBD. Methods: We conducted a population-based case-control study using
      the Rochester Epidemiology Project of Olmsted County, Minnesota. We identified
      736 county residents diagnosed with IBD between 1980 and 2010 who were matched to
      1472 controls, based on age, sex and date of IBD diagnosis. Data on antibiotic
      use between 3 months and 5 years before IBD diagnosis were collected. Logistic
      regression models were used to estimate associations between antibiotic use and
      IBD, and were expressed as adjusted odds ratio [AOR] with 95% confidence interval
      [CI]. Results: Antibiotic use occurred in 455 IBD cases [61.8%] and 495 controls
      [33.6%] [p < 0.001]. In multivariate analysis, there were statistically
      significant associations between antibiotic use and new-onset IBD [AOR, 2.93; 95%
      CI, 2.40-3.58], Crohn's disease [CD] [AOR, 3.01; 2.27-4.00] and ulcerative
      colitis [UC] [AOR, 2.94; 95% CI, 2.23-3.88]. A cumulative duration of antibiotic
      use >= 30 days had the strongest AOR [6.01; 95% CI, 4.34-8.45]. AOR for those
      receiving antibiotics under the age of 18 years was 4.27 [95% CI, 2.39-7.91],
      2.97 for age 18-60 years [2.36-3.75] and 2.72 for age > 60 years [1.60-4.67].
      Conclusions: This population-based case-control study suggests a strong
      association between antibiotic use and the risk of both new-onset CD and new
      onset UC. The risk was increased among all age-onset IBD.

PMID- 29029152
TI  - Surgical Treatment in Childhood-onset Inflammatory Bowel Disease-A Nationwide
      Register-based Study of 4695 Incident Patients in Sweden 2002-2014.
AB  - Background and Aims: The incidence of childhood-onset [< 18 years] inflammatory
      bowel disease [IBD] is increasing worldwide, and some studies suggest that it
      represents a more severe disease phenotype. Few nationwide, population-based
      studies have evaluated the surgical burden in patients with childhood-onset IBD,
      and whether the improved medical treatment has influenced the need for
      gastrointestinal surgery. The aim was to examine whether the surgical treatment
      at any age of patients with childhood-onset IBD has changed over time. Methods:
      In a nationwide cohort study we identified 4695 children [< 18 years] diagnosed
      with incident IBD in 2002-2014 through the Swedish Patient Register [ulcerative
      colitis: n = 2295; Crohn's disease: n = 2174; inflammatory bowel disease
      unclassified: n = 226]. Abdominal [intestinal resections and colectomies] and
      perianal surgeries were identified through the Swedish Patient Register. The
      cumulative incidences of surgeries were calculated using the Kaplan-Meier method.
      Results: In the cohort, 44% were females and 56% males. The median age at
      inflammatory bowel disease diagnosis was 15 years and the maximum age at end of
      follow-up was 31 years. The 3-year cumulative incidence of intestinal surgery was
      5% in patients with ulcerative colitis and 7% in patients with Crohn's disease,
      and lower in children aged < 6 years at inflammatory bowel disease diagnosis [3%]
      than in those aged 15-17 years at diagnosis [7%]. Calendar period of inflammatory
      bowel disease diagnosis was not associated with risk of surgery. Conclusion: Over
      the past 13 years, the risk of surgery in childhood-onset inflammatory bowel
      disease has remained unchanged.

PMID- 29029154
TI  - Interrogating resilience in health systems development.
AB  - The Fourth Global Symposium on Health Systems Research was themed around
      'Resilient and responsive health systems for a changing world.' This commentary
      is the outcome of a panel discussion at the symposium in which the resilience
      discourse and its use in health systems development was critically interrogated.
      The 2014-15 Ebola outbreak in West-Africa added momentum for the wider adoption
      of resilient health systems as a crucial element to prepare for and effectively
      respond to crisis. The growing salience of resilience in development and health
      systems debates can be attributed in part to development actors and
      philanthropies such as the Rockefeller Foundation. Three concerns regarding the
      application of resilience to health systems development are discussed: (1) the
      resilience narrative overrules certain democratic procedures and priority setting
      in public health agendas by 'claiming' an exceptional policy space; (2)
      resilience compels accepting and maintaining the status quo and excludes
      alternative imaginations of just and equitable health systems including the socio
      political struggles required to attain those; and (3) an empirical case study
      from Gaza makes the case that resilience and vulnerability are symbiotic with
      each other rather than providing a solution for developing a strong health
      system. In conclusion, if the normative aim of health policies is to build
      sustainable, universally accessible, health systems then resilience is not the
      answer. The current threats that health systems face demand us to imagine beyond
      and explore possibilities for global solidarity and justice in health.

PMID- 29029153
TI  - Modeling the Environmental Suitability for Aedes (Stegomyia) aegypti and Aedes
      (Stegomyia) albopictus (Diptera: Culicidae) in the Contiguous United States.
AB  - The mosquitoes Aedes (Stegomyia) aegypti (L.)(Diptera:Culicidae) and Ae.
      (Stegomyia) albopictus (Skuse) (Diptera:Culicidae) transmit dengue, chikungunya,
      and Zika viruses and represent a growing public health threat in parts of the
      United States where they are established. To complement existing mosquito
      presence records based on discontinuous, non-systematic surveillance efforts, we
      developed county-scale environmental suitability maps for both species using
      maximum entropy modeling to fit climatic variables to county presence records
      from 1960-2016 in the contiguous United States. The predictive models for Ae.
      aegypti and Ae. albopictus had an overall accuracy of 0.84 and 0.85,
      respectively. Cumulative growing degree days (GDDs) during the winter months, an
      indicator of overall warmth, was the most important predictive variable for both
      species and was positively associated with environmental suitability. The number
      (percentage) of counties classified as environmentally suitable, based on models
      with 90 or 99% sensitivity, ranged from 1,443 (46%) to 2,209 (71%) for Ae.
      aegypti and from 1,726 (55%) to 2,329 (75%) for Ae. albopictus. Increasing model
      sensitivity results in more counties classified as suitable, at least for summer
      survival, from which there are no mosquito records. We anticipate that Ae.
      aegypti and Ae. albopictus will be found more commonly in counties classified as
      suitable based on the lower 90% sensitivity threshold compared with the higher
      99% threshold. Counties predicted suitable with 90% sensitivity should therefore
      be a top priority for expanded mosquito surveillance efforts while still keeping
      in mind that Ae. aegypti and Ae. albopictus may be introduced, via accidental
      transport of eggs or immatures, and potentially proliferate during the warmest
      part of the year anywhere within the geographic areas delineated by the 99%
      sensitivity model.

PMID- 29029155
TI  - The Role of Phylogenetics as a Tool to Predict the Spread of Resistance.
AB  - Drug resistance mutations emerge in genetic sequences of HIV through drug
      selective pressure. Drug resistance can be transmitted. In this review we discuss
      phylogenetic methods used to study the emergence of drug resistance and the
      spread of resistant viruses.

PMID- 29029157
TI  - Stings of the Ant Wasmannia auropunctata (Hymenoptera: Formicidae) as Cause of
      Punctate Corneal Lesions in Humans and Other Animals.
AB  - Numerous researchers have observed a form of punctate corneal lesions causing
      leukomas (corneal opacities) in humans, domestic animals, and wild animals in
      different parts of the world. This condition has been reported under different
      names, including West Indian (or Caribbean) punctate keratopathy, West Indian
      dots, tropical punctate keratopathy, Rice's keratopathy, Florida keratopathy, and
      Florida spots. Many of these cases, appear to have a common cause, the stings of
      a small red ant, Wasmannia auropunctata (Hymenoptera: Formicidae), originally
      from the Neotropics, but spread to other parts of the world through human
      commerce. The purpose of this article is to link disparate literature on punctate
      or nummular corneal lesions published in medical, veterinary, wildlife, and
      entomology journals, because many researchers seem largely unaware of the
      literature from disciplines other than their own. Recognizing a common cause of
      this corneal condition is important to insure proper medical treatment and foster
      efforts to limit the spread and negative impact of W. auropunctata.

PMID- 29029156
TI  - Detailed Transmission Network Analysis of a Large Opiate-Driven Outbreak of HIV
      Infection in the United States.
AB  - In January 2015, an outbreak of undiagnosed human immunodeficiency virus (HIV)
      infections among persons who inject drugs (PWID) was recognized in rural Indiana.
      By September 2016, 205 persons in this community of approximately 4400 had
      received a diagnosis of HIV infection. We report results of new approaches to
      analyzing epidemiologic and laboratory data to understand transmission during
      this outbreak. HIV genetic distances were calculated using the polymerase region.
      Networks were generated using data about reported high-risk contacts, viral
      genetic similarity, and their most parsimonious combinations. Sample collection
      dates and recency assay results were used to infer dates of infection.
      Epidemiologic and laboratory data each generated large and dense networks.
      Integration of these data revealed subgroups with epidemiologic and genetic
      commonalities, one of which appeared to contain the earliest infections.
      Predicted infection dates suggest that transmission began in 2011, underwent
      explosive growth in mid-2014, and slowed after the declaration of a public health
      emergency. Results from this phylodynamic analysis suggest that the majority of
      infections had likely already occurred when the investigation began and that
      early transmission may have been associated with sexual activity and injection
      drug use. Early and sustained efforts are needed to detect infections and prevent
      or interrupt rapid transmission within networks of uninfected PWID.

PMID- 29029159
TI  - Impact evaluation of free delivery care on maternal health service utilisation
      and neonatal health in Nepal.
AB  - Nepal introduced free delivery services for births in public facilities in 2005
      in 25 districts with the intervention initially restricted to women with less
      than two living children and/or women with obstetric complications. After
      November 2007, eligibility conditions were relaxed to include all women, and the
      programme was later expanded to cover an additional 50 districts in December
      2008. We exploit the phased expansion of the free birth delivery programme to
      identify its impact on place of delivery, the presence of skilled birth
      attendants (SBAs) and neonatal mortality using difference-in-difference methods,
      on data for 4457 live-births reported between 2001 and 2008 from Nepal
      Demographic and Health Surveys for 2006 and 2011. Programme impacts were
      estimated for: (1) initial implementation until the relaxation of eligibility
      criteria to include all women in November 2007 (early phase); and (2) initial
      implementation until the programme was expanded nationwide in December 2008
      (longer phase). Early implementing districts were treatment districts, while late
      implementing hill districts were control districts. In the early phase, the
      likelihood of delivery by SBAs was 5.6 percentage points higher (95%CI 0.002,
      0.111) and the likelihood of delivery in a public facility was 5.1 percentage
      points higher (95%CI -0.003, 0.106) in treatment districts compared with control
      districts. The programme lowered the likelihood of neonatal mortality by 4.0 (
      0.072, -0.009) percentage points for women with less than two living children and
      by 6.9 percentage points (95%CI -0.104, -0.035) for women from lower castes and
      indigenous groups in treatment districts compared with women in control
      districts, during the early phase. Programme effects on use of public facilities
      for births and deliveries attended by SBAs were not sustained over a longer
      exposure period. The results on neonatal mortality persisted with longer
      programme exposure, although the effects were smaller in magnitude.

PMID- 29029158
TI  - Genetic Interaction Network as an Important Determinant of Gene Order in Genome
      Evolution.
AB  - Although it is generally accepted that eukaryotic gene order is not random, the
      basic principles of gene arrangement on a chromosome remain poorly understood.
      Here, we extended existing population genetics theories that were based on two
      locus models and proposed a hypothesis that genetic interaction networks drive
      the evolution of eukaryotic gene order. We predicted that genes with positive
      epistasis would move toward each other in evolution, during which a negative
      correlation between epistasis and gene distance formed. We tested and confirmed
      our prediction with computational simulations and empirical data analyses.
      Importantly, we demonstrated that gene order in the budding yeast could be
      successfully predicted from the genetic interaction network. Taken together, our
      study reveals the role of the genetic interaction network in the evolution of
      gene order, extends our understanding of the encoding principles in genomes, and
      potentially offers new strategies to improve synthetic biology.

PMID- 29029161
TI  - Society for Glycobiology Awards-2017.

PMID- 29029160
TI  - Characterization of the Actinobacillus pleuropneumoniae SXT-related integrative
      and conjugative element ICEApl2 and analysis of the encoded FloR protein:
      hydrophobic residues in transmembrane domains contribute dynamically to
      florfenicol and chloramphenicol efflux.
AB  - Objectives: To characterize ICEApl2, an SXT-related integrative and conjugative
      element (ICE) found in a clinical isolate of the porcine pathogen Actinobacillus
      pleuropneumoniae, and analyse the functional nature of the encoded FloR. Methods:
      ICEApl2 was identified in the genome of A. pleuropneumoniae MIDG3553. Functional
      analysis was done using conjugal transfer experiments. MIDG3553 was tested for
      susceptibility to the antimicrobials for which resistance genes are present in
      ICEApl2. Lack of florfenicol/chloramphenicol resistance conferred by the encoded
      FloR protein was investigated by cloning and site-directed mutagenesis
      experiments in Escherichia coli. Results: ICEApl2 is 92660 bp and contains 89
      genes. Comparative sequence analysis indicated that ICEApl2 is a member of the
      SXT/R391 ICE family. Conjugation experiments showed that, although ICEApl2 is
      capable of excision from the chromosome, it is not self-transmissible. ICEApl2
      encodes the antimicrobial resistance genes floR, strAB, sul2 and dfrA1, and
      MIDG3553 is resistant to streptomycin, sulfisoxazole and trimethoprim, but not
      florfenicol or chloramphenicol. Cloning and site-directed mutagenesis of the floR
      gene revealed the importance of the nature of the hydrophobic amino acid residues
      at positions 160 and 228 in FloR for determining resistance to florfenicol and
      chloramphenicol. Conclusions: Our results indicate that the nature of hydrophobic
      residues at positions 160 and 228 of FloR contribute dynamically to specific
      efflux of florfenicol and chloramphenicol, although some differences in
      resistance levels may depend on the bacterial host species. This is also, to our
      knowledge, the first description of an SXT/R391 ICE in A. pleuropneumoniae or any
      member of the Pasteurellaceae.

PMID- 29029163
TI  - Toxicity and Sublethal Effects of Cantharidin on Musca domestica (Diptera:
      Muscidae).
AB  - The house fly, Musca domestica L. (Diptera: Muscidae), is a major pest of medical
      and veterinary importance all over the world. Management efforts for house flies
      are usually compromised owing to their resistance to many groups of conventional
      insecticides. Cantharidin, a natural toxin produced by meloid beetles, is a
      biopesticide with a reported toxicity to some insect pests including house flies.
      However, the effects of cantharidin on biological and fitness parameters of house
      flies have not yet been investigated. In the present study, we investigated the
      toxicity and sublethal effects of cantharidin on biological parameters of house
      flies for two consecutive generations. The results revealed that the values of
      LC50, LC25, LC10, and LC2 against house flies were to be 2.45, 1.23, 0.66, and
      0.30 mg/liter, respectively. Sublethal effects of these concentrations on the
      development and reproduction parameters of house flies revealed that cantharidin
      reduced population growth by affecting pupation rate, adult emergence, and by
      lengthening developmental time. The female ratio, fecundity, egg hatching, and
      survival of adult flies were significantly reduced at LC2, LC10, LC25, and LC50
      of cantharidin when compared with the control group. Furthermore, the increase in
      concentration of cantharidin had a significant effect on reducing the mean values
      of mean relative growth rate, net reproductive rate (Ro), intrinsic rate of
      natural increase (rm), and biotic potential (bp). In conclusion, the results of
      this study revealed the toxicity of cantharidin against house flies and the
      adverse effects of sublethal concentrations on biological parameters which may
      have positive implications for effective management of house flies.

PMID- 29029162
TI  - Aberrant Global and Jagged-Mediated Notch Signaling Disrupts Segregation Between
      wt1-Expressing and Steroidogenic Tissues in Zebrafish.
AB  - Although the zebrafish interrenal tissue has been used as a model for
      steroidogenesis and genesis of the adrenal gland, its specification and
      morphogenesis remains largely unclear. In the present study, we explored how the
      Wilms tumor 1 (WT1)-expressing cells are segregated from the SF-1-expressing
      steroidogenic cells in the zebrafish model. The interrenal tissue precursors
      expressing ff1b, the equivalent of mammalian SF-1, were derived from wt1
      expressing pronephric primordia in the zebrafish embryo. Through histochemistry
      and in situ hybridization, we demonstrated that the size of functionally
      differentiated interrenal tissue was substantially increased on global inhibition
      of the Notch signaling pathway and was accompanied by a disrupted segregation
      between the wt1- and ff1b-expressing cells. As the Notch pathway was
      conditionally activated during interrenal specification, differentiation, but not
      ff1b expression, of interrenal tissue was drastically compromised. In embryos
      deficient for Notch ligands jagged 1b and 2b, transgenic reporter activity of
      wt1b promoter was detected within the steroidogenic interrenal tissue. In
      conclusion, our results indicate that Jagged-Notch signaling is required (1) for
      segregation between wt1-expressing cells and differentiated steroidogenic tissue;
      and (2) to modulate the extent of functional differentiation in the steroidogenic
      interrenal tissue.

PMID- 29029165
TI  - Depicting new pharmacological strategies for familial hypercholesterolaemia
      involving lipoprotein (a).
AB  - Approximately 35 million people worldwide suffer from heterozygous familial
      hypercholesterolaemia (HeFH), a condition characterized by genetically determined
      life-long elevation of plasma low-density lipoprotein cholesterol (LDL-C). One in
      three of these patients also inherit an elevated plasma concentration of
      lipoprotein (a) [Lp(a)], a lipoprotein particle with atherogenic, inflammatory
      and prothrombotic properties. Accordingly, the combination of high plasma LDL-C
      and Lp(a) can markedly accelerate premature atherosclerotic cardiovascular
      disease (ASCVD). Neither statin nor ezetimibe lowers Lp(a), so that FH patients
      with high Lp(a) remain at high residual risk of ASCVD. PCSK9 monoclonal
      antibodies are indicated for HeFH patients not at guideline-recommended LDL-C
      target, but only lower Lp(a) concentration by 15-30%. Recent trials employing
      apo(a) antisense therapy show more potent (up to 90%) reductions in plasma Lp(a).
      The combination of PCSK9 inhibitor and apo(a) antisense therapy appears the
      optimal strategy for mitigating residual risk of ASCVD in HeFH patients with high
      Lp(a).

PMID- 29029164
TI  - Aging Parents' Disabilities and Daily Support Exchanges With Middle-Aged
      Children.
AB  - Background and Objectives: Aging parents often incur disabilities in activities
      of daily living, which may limit their ability to give support and necessitate
      increased support from middle-aged children. Research has predominantly assessed
      disabled parents' retrospective reports of receiving support, but we know little
      about their daily support exchanges with middle-aged children. This study
      examined practical support, emotional support, and advice that aging parents with
      and without disabilities provided and received from middle-aged children, and
      links between these support exchanges and parents' daily mood. Research Design
      and Methods: Aging parents (N = 202, Mage = 79.86) from the Family Exchanges
      Study II indicated their disabilities and background characteristics. They also
      reported daily exchanges of practical, emotional support, and advice with each
      middle-aged child and their daily mood for 7 days. Results: Multilevel models
      revealed that aging parents suffering disabilities were equally likely to provide
      each type of support but more likely to receive practical support. Aging parents'
      disabilities seemed to buffer the effects of these support exchanges, such that
      parents with disabilities versus parents without disabilities reported less
      negative mood when providing practical support or emotional support, and more
      positive mood when receiving practical support. Discussion and Implications:
      Exploring the role of aging parents' disabilities in their daily support
      exchanges with middle-aged children expands on the literature of late-life
      disabilities and parent-child ties. Despite increasing disabilities, aging
      parents continue to engage in support exchanges with middle-aged children in
      daily life and these parents appear to benefit from such involvement.

PMID- 29029167
TI  - 124 Low-Back Pain Relief With a New 32-Contact Surgical Lead and Neural Targeting
      Algorithm.

PMID- 29029166
TI  - Beyond Antigenic Match: Possible Agent-Host and Immuno-epidemiological Influences
      on Influenza Vaccine Effectiveness During the 2015-2016 Season in Canada.
AB  - Background: Vaccine effectiveness (VE) estimates for 2015-2016 seasonal influenza
      vaccine are reported from Canada's Sentinel Practitioner Surveillance Network
      (SPSN). This season was characterized by a delayed 2009 pandemic influenza
      A(H1N1) virus (A[H1N1]pdm09) epidemic and concurrent influenza B(Victoria) virus
      activity. Potential influences on VE beyond antigenic match are explored,
      including viral genomic variation, birth cohort effects, prior vaccination, and
      epidemic period. Methods: VE was estimated by a test-negative design comparing
      the adjusted odds ratio for influenza test positivity among vaccinated compared
      to unvaccinated participants. Vaccine-virus relatedness was assessed by gene
      sequencing and hemagglutination inhibition assay. Results: Analyses included 596
      influenza A(H1N1)pdm09 and 305 B(Victoria) cases and 926 test-negative controls.
      A(H1N1)pdm09 viruses were considered antigenically related to vaccine (unchanged
      since 2009), despite phylogenetic clustering within emerging clade 6B.1. The
      adjusted VE against A(H1N1)pdm09 was 43% (95% confidence interval [CI], 25%-57%).
      Compared to other age groups, VE against A(H1N1)pdm09 was lower for adults born
      during 1957-1976 (25%; 95% CI, -16%-51%). The VE against A(H1N1)pdm09 was also
      lower for participants consecutively vaccinated during both the current and prior
      seasons (41%; 95% CI, 18%-57%) than for those vaccinated during the current
      season only (75%; 95% CI, 45%-88%), and the VE among participants presenting in
      March-April 2016 (19%; 95% CI, -15%-44%) was lower than that among those
      presenting during January-February 2016 (62%; 95% CI, 44%-74%). The adjusted VE
      for B(Victoria) viruses was 54% (95% CI, 32%-68%), despite lineage-level mismatch
      to B(Yamagata) vaccine. The further variation in VE as observed for A(H1N1)pdm09
      was not observed for B(Victoria). Conclusions: Influenza VE findings may require
      consideration of other agent-host and immuno-epidemiologic influences on vaccine
      performance beyond antigenic match, including viral genomic variation, repeat
      vaccination, birth (immunological) cohort effects, and potential within-season
      waning of vaccine protection.

PMID- 29029168
TI  - Effects of Foliar Insecticides on Leaf-Level Spectral Reflectance of Soybean.
AB  - Pest-induced changes in plant reflectance are crucial for the development of pest
      management programs using remote sensing. However, it is unknown if plant
      reflectance data is also affected by foliar insecticides applied for pest
      management. Our study assessed the effects of foliar insecticides on leaf
      reflectance of soybean. A 2-yr field trial and a greenhouse trial were conducted
      using randomized complete block and completely randomized designs, respectively.
      Treatments consisted of an untreated check, a new systemic insecticide
      (sulfoxaflor), and two representatives of the most common insecticide classes
      used for soybean pest management in the north-central United States (i.e., lambda
      cyhalothrin and chlorpyrifos). Insecticides were applied at labeled rates
      recommended for controlling soybean aphid; the primary insect pest in the north
      central United States. Leaf-level reflectance was measured using ground-based
      spectroradiometers. Sulfoxaflor affected leaf reflectance at some red and blue
      wavelengths but had no effect at near-infrared or green wavelengths. Chlorpyrifos
      affected leaf reflectance at some green, red, and near-infrared wavelengths but
      had no effect at blue wavelengths. lambda-cyhalothrin had the least effect on
      spectral reflectance among the insecticides, with changes to only a few near
      infrared wavelengths. Our results showing immediate and delayed effects of foliar
      insecticides on soybean reflectance indicate that application of some
      insecticides may confound the use of remote sensing for detection of not only
      insects but also plant diseases, nutritional and water deficiencies, and other
      crop stressors.

PMID- 29029169
TI  - A Family Affair: Family Typologies of Problems and Midlife Well-Being.
AB  - Background and Objectives: Midlife adults are a "pivot" generation, responding to
      parents' and grown children's problems. Yet, some midlife adults may have
      families where multiple members suffer sorrows, whereas other midlife adults may
      have families with few problems. This study examined: (a) typologies of problems
      across generations and (b) associations between profiles of problems and midlife
      adults' well-being. Research Design and Methods: Midlife adults (N = 633)
      reported their own, each parent's (n = 868), and grown child's (n = 1,785)
      physical (e.g., injury, cancer), psychological (e.g., anxiety, addiction), and
      lifestyle problems (e.g., divorce, job loss), and parents' functional
      disabilities. Midlife adults reported their own depressive symptoms. Results:
      Latent profile analysis revealed four family typologies: (a) lowest problems
      across generations (n = 364), (b) offspring and midlife adult moderate problems,
      parent high physical problems and disability (n = 165), (c) offspring and parent
      moderate problems (n = 90), and (d) offspring highest problems (n = 14). Midlife
      adults in the lowest problems group (Profile a) reported higher income and fewer
      depressive symptoms than midlife adults in the other groups. Discussion and
      Implications: Midlife adults cope with challenges when grown children or parents
      suffer problems, and their well-being may suffer as a result. In this study,
      regardless of the profile, higher problems in either generation were associated
      with more depressive symptoms for midlife adults.

PMID- 29029170
TI  - Use of a structured panel process to define antimicrobial prescribing
      appropriateness in critical care.
AB  - Background: Antimicrobial prescribing is frequently reported as appropriate or
      inappropriate, particularly in the ICU. However, the definitions used are non
      standardized and lack validity and reliability. Objectives: To develop
      standardized definitions of appropriateness for antimicrobial prescribing in the
      critical care setting. Methods: We used consensus-based modified Delphi and RAND
      appropriateness methodology to develop criteria to define appropriateness of
      antimicrobial prescribing. A multiphased approach with an online questionnaire
      followed by a facilitated in-person meeting was utilized and included clinicians
      from a variety of practice areas (e.g. surgeons, infectious diseases specialists,
      intensivists, transplant specialists and pharmacists). Results: There were a
      total of 23 criteria agreed upon to define the following categories of
      antimicrobial prescribing: appropriate; effective but unnecessary; inappropriate;
      and under-treatment. Conclusions: These standardized criteria for appropriateness
      may be generalizable to other patient populations and utilized with other tools
      to adjudicate prescribing practices.

PMID- 29029172
TI  - DnaSP 6: DNA Sequence Polymorphism Analysis of Large Data Sets.
AB  - We present version 6 of the DNA Sequence Polymorphism (DnaSP) software, a new
      version of the popular tool for performing exhaustive population genetic analyses
      on multiple sequence alignments. This major upgrade incorporates novel
      functionalities to analyze large data sets, such as those generated by high
      throughput sequencing technologies. Among other features, DnaSP 6 implements: 1)
      modules for reading and analyzing data from genomic partitioning methods, such as
      RADseq or hybrid enrichment approaches, 2) faster methods scalable for high
      throughput sequencing data, and 3) summary statistics for the analysis of multi
      locus population genetics data. Furthermore, DnaSP 6 includes novel modules to
      perform single- and multi-locus coalescent simulations under a wide range of
      demographic scenarios. The DnaSP 6 program, with extensive documentation, is
      freely available at http://www.ub.edu/dnasp.

PMID- 29029171
TI  - Effect of HIV on the Frequency and Number of Mycobacterium tuberculosis-Specific
      CD4+ T Cells in Blood and Airways During Latent M. tuberculosis Infection.
AB  - Human immunodeficiency virus type 1 (HIV) infection substantially increases the
      risk of developing tuberculosis. There is extensive depletion of Mycobacterium
      tuberculosis-specific CD4+ T cells in blood during early HIV infection, but
      little is known about responses in the lungs at this stage. Given that mucosal
      organs are a principal target for HIV-mediated CD4+ T-cell destruction, we
      investigated M. tuberculosis-specific responses in bronchoalveolar lavage (BAL)
      from persons with latent M. tuberculosis infection and untreated HIV coinfection
      with preserved CD4+ T-cell counts. M. tuberculosis-specific CD4+ T-cell cytokine
      (interferon gamma, tumor necrosis factor alpha, and interleukin 2) responses were
      discordant in frequency and function between BAL and blood. Responses in BAL were
      15-fold lower in HIV-infected persons as compared to uninfected persons (P =
      .048), whereas blood responses were 2-fold lower (P = .006). However, an increase
      in T cells in the airways in HIV-infected persons resulted in the overall number
      of M. tuberculosis-specific CD4+ T cells in BAL being similar. Our study
      highlights the important insights gained from studying M. tuberculosis immunity
      at the site of disease during HIV infection.

PMID- 29029173
TI  - First Report of Aedes (Stegomyia) albopictus (Skuse) (Diptera: Culicidae), the
      Asian Tiger Mosquito, in Ecuador.
AB  - Aedes (Stegomyia) albopictus (Skuse), (Diptera: Culicidae), the Asian tiger
      mosquito, is one of the most widespread invasive vector-borne disease insect in
      tropical and temperate zones. This species has invaded the Americas over the past
      3 decades and has spread to six countries. We report Ae. albopictus in Guayaquil
      city, the first time it has been identified in Ecuador. Outdoor BG-Sentinel traps
      without lures collected a total of 21 Ae. albopictus.

PMID- 29029174
TI  - Statistical Package for Growth Rates Made Easy.
AB  - Growth rates are an important tool in microbiology because they provide high
      throughput fitness measurements. The release of GrowthRates, a program that uses
      the output of plate reader files to automatically calculate growth rates, has
      facilitated experimental procedures in many areas. However, many sources of
      variation within replicate growth rate data exist and can decrease data
      reliability. We have developed a new statistical package, CompareGrowthRates
      (CGR), to enhance the program GrowthRates and accurately measure variation in
      growth rate data sets. We define a metric, Variability-score (V-score), that can
      help determine if variation within a data set might result in false
      interpretations. CGR also uses the bootstrap method to determine the fraction of
      bootstrap replicates in which a strain will grow the fastest. We illustrate the
      usage of CGR with growth rate data sets similar to those in Mira, Meza, et al.
      (Adaptive landscapes of resistance genes change as antibiotic concentrations
      change. Mol Biol Evol. 32(10): 2707-2715). These statistical methods are
      compatible with the analytic methods described in Growth Rates Made Easy and can
      be used with any set of growth rate output from GrowthRates.

PMID- 29029175
TI  - Beyond Antigenic Match: Moving Toward Greater Understanding of Influenza Vaccine
      Effectiveness.

PMID- 29029176
TI  - Spontaneous mechanical rupture of a papillary muscle effectively resolved by
      mitral valve repair.
AB  - We report a case of spontaneous mechanical papillary muscle rupture. In theory,
      the papillary muscle works as a shock absorber that compensates for geometric
      changes of left ventricular wall. We believe that the aetiology of papillary
      muscle rupture, in this case, is linked to the physical and mechanical strains
      exerted on the papillary. We performed a mitral valve repair with excellent short
      and long-term results.

PMID- 29029177
TI  - Influence of Traditional Management and Environmental Variables on Mediterranean
      Saproxylic Beetle Assemblages.
AB  - Mediterranean oak forests of the Iberian Peninsula host a great diversity of
      saproxylic beetles. For centuries, humans have carried out traditional management
      practices in this area, at both habitat and tree level, causing changes in forest
      structure. The aim of this study was to evaluate the anthropic effect of these
      traditional practices on saproxylic beetle diversity by measuring a set of
      environmental variables related to forest structure at both plot and tree level.
      Fauna was collected using window traps over a period of 12 mo. Multiple
      regression procedures showed which variables significantly affected the diversity
      of the studied assemblage. Our results demonstrated that the different metrics
      used to assess the diversity of assemblages responded variably depending on the
      management strategies applied and the level at which they were carried out.
      Certain management practices that disrupted the landscape from its natural state,
      such as the introduction of livestock or the local removal of particular trees,
      maximized species richness but, nevertheless, had a negative effect on the rest
      of diversity metrics analyzed. However, other practices such as pollarding, which
      involves the suppression of the main branch of the tree, had a positive effect on
      all diversity metrics evaluated as it promoted the formation of potential
      microhabitats for saproxylic fauna. We concluded that not all types and degrees
      of traditional forest management favor saproxylic beetle diversity and that
      different diversity metrics should be taken into consideration in future
      strategies for the protection and conservation of this fauna.

PMID- 29029178
TI  - Expansion of Viral Load Testing and the Potential Impact on Human
      Immunodeficiency Virus Drug Resistance.
AB  - Increasing the volume, strengthening the quality, and proactively using data of
      human immunodeficiency virus (HIV) load testing are pivotal to limiting the
      threat of HIV drug resistance (HIVDR) accumulation,and allow for optimal case
      based HIVDR surveillance. Triangulation of viral load (VL) and HIVDR testing data
      could be pursued to answer key questions and translate data and results for
      program and public policy. Identification of virologic failure and early
      management mitigates the greater risk of HIVDR. Routine VL monitoring and
      evaluation systems are necessary, and countries should consider reviewing system
      requirements, structural needs, and procedural and technical factors for the
      entire VL cascade, with special emphasis on post-test result use.

PMID- 29029180
TI  - Cerebral strokes in children on intracorporeal ventricular assist devices:
      analysis of the EUROMACS Registry.
AB  - OBJECTIVES: Little is known about cerebral strokes in paediatric patients
      supported by intracorporeal continuous-flow ventricular assist devices. METHODS:
      We retrospectively investigated patients younger than 19 years of age who were
      treated with an intracorporeal continuous-flow ventricular assist device in the
      European Registry for Patients with Mechanical Circulatory Support (EUROMACS)
      database. The patients were stratified by body surface area in Group 1 [<1.2 m2
      (n = 13)] and Group 2 [>=1.2 m2 (n = 38)]. Cerebral strokes, both ischaemic and
      haemorrhagic, were studied. RESULTS: Of the 2941 patients with ventricular assist
      device (VAD) implants listed in the database, 124 (4%) patients were less than 19
      years of age. Fifty-one of them (2%) were supported with a continuous-flow
      ventricular assist device. Group 1 (6 female and 7 male) had a mean age (+/-SD)
      of 9 +/- 2.3 years compared with 15.6 +/- 1.8 years in Group 2 (21 female and 17
      male). Three (23%) patients died in Group 1 on VAD support, whereas 5 (13%)
      patients died in Group 2 (P = 0.21; log-rank test). Seven (54%) patients with a
      VAD in Group 1 and 17 (45%) patients in Group 2 underwent transplantation (P =
      0.29); of these, 1 (8%) patient recovered (Group 1) with subsequent device
      explantation. The other patients, 2 in Group 1 and 16 in Group 2, were still on
      device support at the time of the analysis. There were no cerebral strokes in
      Group 1, but 4 cerebral strokes (11% of Group 2, 8% of a total of 51 patients in
      Groups 1 and 2 combined) occurred in Group 2 (3 patients died; P = 0.26; log-rank
      test). Taken together, the incidence of cerebral strokes in this paediatric
      cohort of patients with an intracorporeal VAD was 0.1 per patient-year.
      CONCLUSIONS: The incidence of cerebral strokes in children with intracorporeal
      VADs (0.1 per patient-year) seems to be low irrespective of the body surface
      area.

PMID- 29029181
TI  - Characterization of Odorant Receptors from a Non-ditrysian Moth, Eriocrania
      semipurpurella Sheds Light on the Origin of Sex Pheromone Receptors in
      Lepidoptera.

PMID- 29029179
TI  - Sustained Malaria Control Over an 8-Year Period in Papua New Guinea: The
      Challenge of Low-Density Asymptomatic Plasmodium Infections.
AB  - Background: The scale-up of effective malaria control in the last decade has
      resulted in a substantial decline in the incidence of clinical malaria in many
      countries. The effects on the proportions of asymptomatic and submicroscopic
      infections and on transmission potential are yet poorly understood. Methods: In
      Papua New Guinea, vector control has been intensified since 2008, and improved
      diagnosis and treatment was introduced in 2012. Cross-sectional surveys were
      conducted in Madang Province in 2006 (with 1280 survey participants), 2010 (with
      2117 participants), and 2014 (with 2516 participants). Infections were quantified
      by highly sensitive quantitative polymerase chain reaction (PCR) analysis, and
      gametocytes were quantified by reverse-transcription qPCR analysis. Results:
      Plasmodium falciparum prevalence determined by qPCR decreased from 42% in 2006 to
      9% in 2014. The P. vivax prevalence decreased from 42% in 2006 to 13% in 2010 but
      then increased to 20% in 2014. Parasite densities decreased 5-fold from 2006 to
      2010; 72% of P. falciparum and 87% of P. vivax infections were submicroscopic in
      2014. Gametocyte density and positivity correlated closely with parasitemia, and
      population gametocyte prevalence decreased 3-fold for P. falciparum and 29% for
      P. vivax from 2010 to 2014. Conclusions: Sustained control has resulted in
      reduced malaria transmission potential, but an increasing proportion of
      gametocyte carriers are asymptomatic and submicroscopic and represent a challenge
      to malaria control.

PMID- 29029182
TI  - Overlapping Surgeries Are Not Associated With Worse Patient Outcomes:
      Retrospective Multivariate Analysis of 14 872 Neurosurgical Cases Performed at a
      Single Institution.
AB  - BACKGROUND: Overlapping surgeries have recently become a controversial topic.
      OBJECTIVE: To evaluate the effect of overlapping surgeries on patient outcomes.
      METHODS: A retrospective analysis of all neurosurgical procedures performed at a
      single institution from July 2013 to May 2016 was conducted. Variables extracted
      from the electronic medical records included sex, age, procedure type, resident
      years of training, evening case, emergency case, American Society of
      Anesthesiologists Physical Status Score, illness severity, mortality risk, and
      percentage of case overlap. Univariate and multivariate analyses were performed
      for the following primary outcomes: procedure length, length of hospital stay,
      return to operating room (OR), disposition upon discharge, hospital readmission,
      and mortality. Separate analyses were performed for overlap thresholds of 0%,
      20%, 50%, and 100%. RESULTS: A total of 14 872 cases were performed during the
      study period, and all were included in the statistical analyses. Univariate
      analysis showed a benefit for overlapping surgeries in terms of hospital length
      of stay, return to OR, and disposition status (all P < .001). No difference was
      found for hospital readmission or mortality. Overlapping surgeries were
      significantly longer and were staffed by more senior residents (P < .001).
      Multivariate analysis showed a benefit for overlapping surgeries, or no
      difference, for all the measured outcomes except procedure length. CONCLUSION:
      These results reject the hypothesis that overlapping surgeries are predictive of
      worse outcomes. When considered in the context of the current debate regarding
      overlapping surgeries, these results argue against claims that overlapping
      surgeries are dangerous or harmful to patients.

PMID- 29029183
TI  - Evaluation of the Constituents of Vetiver Oil Against Anopheles minimus (Diptera:
      Culicidae), a Malaria Vector in Thailand.
AB  - The development of resistance by mosquitoes to current synthetic compounds has
      resulted in reduced effectiveness of prevention and control methods worldwide. An
      alternative nonchemical based control tools are needed to be evaluated
      particularly plant-derived essential oils. Several components of vetiver oil have
      been documented as insect repellents. However, detailed knowledge of those
      components action against insect remains unknown. In this study, behavioral
      response of Anopheles minimus to four constituents of vetiver oil (valencene,
      terpinen-4-ol, isolongifolene, vetiverol) was evaluated by using the high
      throughput screening assay system. Vetiverol and isolongifolene exhibited strong
      contact irritancy action at 1.0% (80.2% escaping) and 5.0% (81.7% escaping)
      concentration, respectively, while moderate action was found in both valencene
      and terpinen-4-ol at 5.0% (57.6% escaping). Only at 1.0% (0.7 spatial activity
      index [SAI]) and 5.0% (1.0 SAI) of valencene and 0.5% (0.7 SAI) of isolongifolene
      showed spatial repellency activity. High mortality (58.9-98.2%) was recorded in
      all concentration of vetiverol and isolongifolene. Meanwhile, valencene exhibited
      high mortality only at 5.0%, terpinen-4-ol showed very low toxic action (0-4.3%)
      in all concentration. These proved that valencene in vetiver oil is the promising
      constituent that can be developed as an alternative mosquito control mean in
      efforts to prevent disease transmission.

PMID- 29029185
TI  - Patient-reported outcomes in newly diagnosed early rheumatoid arthritis patients
      treated to target with a tocilizumab- or methotrexate-based strategy.
AB  - Objective: To evaluate the effect of initiation of tocilizumab, with or without
      MTX, compared with MTX alone on patient-reported outcomes (PROs), in DMARD-naive
      patients with early RA. Methods: In U-Act-Early, patients initiated treat-to
      target step-up MTX, tocilizumab or tocilizumab plus MTX therapy. PROs assessed
      included the Functional Assessment of Chronic Illness Therapy-Fatigue, 36-item
      Short Form (SF-36), five dimensional EuroQol (EQ-5D) and the Revised Illness
      Perception Questionnaire. Differences between strategy groups over time and
      proportions of patients exceeding minimum clinically important differences (MCID)
      were evaluated. Results: During the 2-year study period, significant improvements
      were found in the tocilizumab strategies in the SF-36 physical component score
      (tocilizumab, P = 0.012; tocilizumab plus MTX, P = 0.044) and EQ-5D score
      (tocilizumab plus MTX, P = 0.020) when compared with the MTX strategy. No
      significant differences were noted in other PROs (P ? 0.052, except for the
      domain 'identity' in the Illness Perception Questionnaire; tocilizumab vs MTX, P
      = 0.048). The proportions of patients achieving MCID in SF-36 physical component
      score were significantly higher at 12 and 52 weeks (P ? 0.049) in the tocilizumab
      arms when compared with the MTX arm. At week 24, the proportion achieving MCID in
      EQ-5D was significantly higher in the tocilizumab plus MTX arm vs the MTX arm (P
      = 0.045). Conclusion: Initiation of treat-to-target tocilizumab therapy resulted
      in significantly improved PROs, especially within the first 24 weeks, when
      compared with initiation of MTX therapy. Also on the patients' level, initiating
      tocilizumab may be considered as a valuable strategy in DMARD-naive patients with
      early RA. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov,
      NCT01034137.

PMID- 29029184
TI  - Low Plasma Adiponectin Concentrations Predict Increases in Visceral Adiposity and
      Insulin Resistance.
AB  - Context: Plasma adiponectin concentration has been shown to be inversely
      associated with body mass index (BMI) and insulin resistance in cross-sectional
      research. However, it is unclear whether adiponectin predicts future body
      composition and insulin resistance. Objective: We aimed to investigate the
      potential relationship between adiponectin concentration and future regional body
      fat distribution and insulin resistance. Design and Setting: This was a community
      based prospective cohort study with 5 years of follow-up. Participants: A total
      of 218 Japanese Americans without diabetes (79 men, 139 women, mean age 51.7 +/-
      10.1 years) were assessed at baseline and after 5 years of follow-up. Main
      Outcome Measures: Abdominal visceral and subcutaneous fat area and thigh
      subcutaneous fat area were measured by computed tomography (CT). Insulin
      resistance was evaluated by homeostasis model assessment 2 of insulin resistance
      (HOMA2-IR). Plasma total adiponectin was measured by radioimmunoassay. Results:
      Baseline adiponectin was inversely associated with abdominal visceral fat area (P
      = 0.037) and HOMA2-IR (P = 0.002) at 5 years in a multiple linear regression
      model after adjustment for baseline traits (including age, sex, BMI, abdominal
      visceral fat area, abdominal subcutaneous fat area, thigh subcutaneous fat area,
      HOMA2-IR) and weight change. However, no association was seen between baseline
      adiponectin concentration and BMI or other CT-measured regional fat depots at 5
      years. Conclusions: Low plasma adiponectin concentration independently predicted
      future abdominal visceral fat accumulation and increased insulin resistance in
      Japanese Americans.

PMID- 29029186
TI  - Improved Algorithmic Complexity for the 3SEQ Recombination Detection Algorithm.
AB  - Identifying recombinant sequences in an era of large genomic databases is
      challenging as it requires an efficient algorithm to identify candidate
      recombinants and parents, as well as appropriate statistical methods to correct
      for the large number of comparisons performed. In 2007, a computation was
      introduced for an exact nonparametric mosaicism statistic that gave high
      precision P values for putative recombinants. This exact computation meant that
      multiple-comparisons corrected P values also had high precision, which is crucial
      when performing millions or billions of tests in large databases. Here, we
      introduce an improvement to the algorithmic complexity of this computation from
      O(mn3) to O(mn2), where m and n are the numbers of recombination-informative
      sites in the candidate recombinant. This new computation allows for recombination
      analysis to be performed in alignments with thousands of polymorphic sites.
      Benchmark runs are presented on viral genome sequence alignments, new features
      are introduced, and applications outside recombination analysis are discussed.

PMID- 29029187
TI  - Evidence for the Selective Basis of Transition-to-Transversion Substitution Bias
      in Two RNA Viruses.
AB  - The substitution rates of transitions are higher than expected by chance relative
      to those of transversions. Many have argued that selection disfavors
      transversions, as nonsynonymous transversions are less likely to conserve
      biochemical properties of the original amino acid. Only recently has it become
      feasible to directly test this selective hypothesis by comparing the fitness
      effects of a large number of transition and transversion mutations. For example,
      a recent study of six viruses and one beta-lactamase gene did not find evidence
      supporting the selective hypothesis. Here, we analyze the relative fitness
      effects of transition and transversion mutations from our recently published
      genome-wide study of mutational fitness effects in influenza virus. In contrast
      to prior work, we find that transversions are significantly more detrimental than
      transitions. Using what we believe to be an improved statistical framework, we
      also identify a similar trend in two HIV data sets. We further demonstrate a
      fitness difference in transition and transversion mutations using four deep
      mutational scanning data sets of influenza virus and HIV, which provided adequate
      statistical power. We find that three of the most commonly cited
      radical/conservative amino acid categories are predictive of fitness, supporting
      their utility in studies of positive selection and codon usage bias. We conclude
      that selection is a major contributor to the transition:transversion substitution
      bias in viruses and that this effect is only partially explained by the greater
      likelihood of transversion mutations to cause radical as opposed to conservative
      amino acid changes.

PMID- 29029189
TI  - Identification of a mutarotase gene involved in D-galactose utilization in
      Aspergillus nidulans.
AB  - Aldose 1-epimerases or mutarotases (EC 5.1.3.3) are catalyzing the
      interconversion of alpha- and beta-anomers of hemiacetals of aldose sugars such
      as D-glucose and D-galactose, and are presumed to play an auxiliary role in
      carbohydrate metabolism as mutarotation occurs spontaneously in watery solutions.
      The first step in the Leloir pathway of D-galactose breakdown is preceded by
      accelerated conversion of beta-D-galactopyranose into the alpha-anomer, the
      substrate of the anomer-specific D-galactose 1-kinase. Here, we identified two
      putative aldose-1-epimerase genes (galmA and galmB) in the model organism
      Aspergillus nidulans, and characterized them upon generation of single- and
      double deletion mutant strains, as well as overexpressing mutants carrying
      multiple copies of either. Assaying cell-free extracts from the galmB single- and
      galm double mutants, we observed that the mutarotation hardly exceeded
      spontaneous anomer conversion, while galmB multicopy strains displayed higher
      activities than the wild type, increasing with the copy number. When grown on D
      galactose in submerged cultures, biomass formation and D-galactose uptake rates
      in mutants lacking galmB were considerably reduced. None such effects were
      observed studying galmA deletion mutants, which consistently behave like the wild
      type. We conclude that GalmB is the physiologically relevant mutarotase for the
      utilization of D-galactose in A. nidulans.

PMID- 29029188
TI  - An Analysis of the Epidemic of Klebsiella pneumoniae Carbapenemase-Producing K.
      pneumoniae: Convergence of Two Evolutionary Mechanisms Creates the "Perfect
      Storm".
AB  - Background: Carbapenem resistance is a critical healthcare challenge worldwide.
      Particularly concerning is the widespread dissemination of Klebsiella pneumoniae
      carbapenemase (KPC). Klebsiella pneumoniae harboring blaKPC (KPC-Kpn) is endemic
      in many areas including the United States, where the epidemic was primarily
      mediated by the clonal dissemination of Kpn ST258. We postulated that the spread
      of blaKPC in other regions occurs by different and more complex mechanisms. To
      test this, we investigated the evolution and dynamics of spread of KPC-Kpn in
      Colombia, where KPC became rapidly endemic after emerging in 2005. Methods: We
      sequenced the genomes of 133 clinical isolates recovered from 24 tertiary care
      hospitals located in 10 cities throughout Colombia, between 2002 (before the
      emergence of KPC-Kpn) and 2014. Phylogenetic reconstructions and evolutionary
      mapping were performed to determine temporal and genetic associations between the
      isolates. Results: Our results indicate that the start of the epidemic was driven
      by horizontal dissemination of mobile genetic elements carrying blaKPC-2,
      followed by the introduction and subsequent spread of clonal group 258 (CG258)
      isolates containing blaKPC-3. Conclusions: The combination of 2 evolutionary
      mechanisms of KPC-Kpn within a challenged health system of a developing country
      created the "perfect storm" for sustained endemicity of these multidrug-resistant
      organisms in Colombia.

PMID- 29029190
TI  - Pharmacokinetics of IGF-1 in PAPP-A2-Deficient Patients, Growth Response, and
      Effects on Glucose and Bone Density.
AB  - Context: The pregnancy-associated plasma protein A2 (PAPP-A2) cleaves insulinlike
      growth factor binding proteins 3 and 5, releasing free insulinlike growth factor
      1 (IGF-1). Homozygous mutations in PAPP-A2 result in growth failure with elevated
      total but low free IGF-1. Objective: To determine the 24-hour pharmacokinetic
      (PK) profile of free and total IGF-1 after a dose of recombinant human
      insulinlike growth factor 1 (rhIGF-1). We describe the growth response and
      effects on glucose metabolism and bone mineral density (BMD) after 1 year of
      rhIGF-1 therapy. Design and Patients: Three affected siblings, their heterozygous
      parents, and two healthy controls participated. The subjects received a dose of
      rhIGF-1, followed by serial blood samples collected over 24 hours. The two
      younger siblings were started on rhIGF-1 treatment. An oral glucose tolerance
      test and dual-energy X-ray absorptiometry scans were obtained at baseline and
      after 1 year of treatment. Results: Subcutaneous administration of rhIGF-1
      increased the concentration of free and total IGF-1 in patients with PAPP-A2
      deficiency. The PK profile was comparable in all participants. At baseline, all
      three subjects demonstrated insulin resistance and below-average BMD. Treatment
      with rhIGF-1 is ongoing in the youngest patient but was discontinued in his
      brother because of the development of pseudotumor cerebri. The treated patient
      had an increase in height velocity from 3.0 to 6.2 cm/y, resolution of insulin
      resistance, and an increase in total body BMD. Conclusions: rhIGF-1 at standard
      dosages resulted in similar PK characteristics in patients with PAPP-A2
      deficiency, heterozygous relatives, and healthy controls. The youngest affected
      patient experienced a modest growth response to therapy with rhIGF-1, as well as
      beneficial effects on glucose metabolism and bone mass.

PMID- 29029191
TI  - Evaluating the Neolithic Expansion at Both Shores of the Mediterranean Sea.
AB  - During the Neolithic, human populations underwent cultural and technological
      developments that led to an agricultural revolution. Although the population
      genetics and evolution of European Neolithic populations have been extensively
      studied, little is known regarding the Neolithic expansion in North Africa with
      respect to Europe. One could expect that the different environmental and
      geological conditions at both shores of the Mediterranean Sea could have led to
      contrasting expansions. In order to test this hypothesis, we compared the
      Neolithic expansion in Europe and North Africa accounting for possible migration
      between them through the Strait of Gibraltar. We analyzed the entire X chromosome
      of 580 individuals from 20 populations spatially distributed along the North of
      Africa and Europe. Next, we applied approximate Bayesian computation based on
      extensive spatially explicit computer simulations to select among alternative
      scenarios of migration through the Strait of Gibraltar and to estimate population
      genetics parameters in both expansions. Our results suggest that, despite being
      more technologically advanced, Neolithic populations did not expand faster than
      Paleolithic populations, which could be interpreted as a consequence of a more
      sedentary lifestyle. We detected reciprocal Neolithic migration between the
      Iberian Peninsula and North Africa through the Strait of Gibraltar.
      Counterintuitively, we found that the studied Neolithic expansions presented
      similar levels of carrying capacity and migration, and occurred at comparable
      speeds, suggesting a similar demic process of substitution of hunter-gatherer
      populations. Altogether, the Neolithic expansion through both Mediterranean
      shores was not so different, perhaps because these populations shared similar
      technical abilities and lifestyle patterns.

PMID- 29029192
TI  - Paracoccidioidomycosis Associated With a Heterozygous STAT4 Mutation and Impaired
      IFN-gamma Immunity.
AB  - Background: Mutations in genes affecting interferon-gamma (IFN-gamma) immunity
      have contributed to understand the role of IFN-gamma in protection against
      intracellular pathogens. However, inborn errors in STAT4, which controls
      interleukin-12 (IL-12) responses, have not yet been reported. Our objective was
      to determine the genetic defect in a family with a history of
      paracoccidioidomycosis. Methods: Genetic analysis was performed by whole-exome
      sequencing and Sanger sequencing. STAT4 phosphorylation (pSTAT4) and
      translocation to the nucleus, IFN-gamma release by patient lymphocytes, and
      microbicidal activity of patient monocytes/macrophages were assessed. The effect
      on STAT4 function was evaluated by site-directed mutagenesis using a
      lymphoblastoid B cell line (B-LCL) and U3A cells. Results: A heterozygous
      missense mutation, c.1952 A>T (p.E651V) in STAT4 was identified in the index
      patient and her father. Patient's and father's lymphocytes showed reduced pSTAT4,
      nuclear translocation, and impaired IFN-gamma production. Mutant B-LCL and U3A
      cells also displayed reduced pSTAT4. Patient's and father's peripheral blood
      mononuclear cells and macrophages demonstrated impaired fungicidal activity
      compared with those from healthy controls that improved in the presence of
      recombinant human IFN-gamma, but not rhIL-12. Conclusion: Our data suggest
      autosomal dominant STAT4 deficiency as a novel inborn error of IL-12-dependent
      IFN-gamma immunity associated with susceptibility to paracoccidioidomycosis.

PMID- 29029193
TI  - Sex and Iron Modify Fibroblast Growth Factor 23 Concentration in 1-Year-Old
      Children.
AB  - Context: Fibroblast growth factor 23 (FGF23) plays an important role in phosphate
      homeostasis, but its regulation is inadequately characterized. Objective: To
      examine FGF23 regulators, especially sex and iron status, in early childhood.
      Design: A cross-sectional study involving 1-year-old children. Setting and
      Participants: Healthy term infants with a birth weight appropriate for
      gestational age were recruited to an ongoing vitamin D trial at Katiloopisto
      Maternity Hospital, Helsinki, Finland. At 12-month follow-up visits, serum FGF23,
      25-hydroxyvitamin D (25OHD), phosphate, ionized calcium, parathyroid hormone, and
      iron status were measured. All 721 children (51% girls) with complete data were
      included. Main Outcome Measures: Intact and C-terminal FGF23 concentrations and
      iron status at 1 year of age. Results: Intact FGF23 was greater in girls than in
      boys [median, 44.4 pg/mL; interquartile range (IQR), 36.8 to 51.9; median, 40.9
      pg/mL; IQR, 34.5 to 49.0, respectively; P < 0.001]. C-terminal FGF23 was similar
      in boys and girls (median, 2.8 pmol/L; IQR, 2.1 to 3.7; median, 2.9 pmol/L; IQR,
      2.2 to 3.7, respectively; P = 0.393). The iron concentration was positively
      associated with intact FGF23 and was the strongest modifier of intact FGF23
      (regression coefficient, 0.498; 95% confidence interval, 0.333 to 0.663; P <
      0.001) with ferritin, season, ionized calcium, 25OHD, and sex as other
      covariates. The association between iron and C-terminal FGF23 was inversely
      related (regression coefficient, -0.072; 95% confidence interval, -0.092 to 
      0.051; P < 0.001). Conclusions: At 1 year of age, FGF23 status was different in
      girls and boys, with intact FGF23 concentrations higher in girls. Iron modified
      FGF23 concentrations, with intact FGF23 higher and C-terminal lower, in those
      with greater iron concentrations.

PMID- 29029194
TI  - Envelope proteome changes driven by RamA overproduction in Klebsiella pneumoniae
      that enhance acquired beta-lactam resistance.
AB  - Objectives: In Klebsiella pneumoniae, overproduction of RamA results in reduced
      envelope permeability and reduced antimicrobial susceptibility but clinically
      relevant resistance is rarely observed. Here we have tested whether RamA
      overproduction can enhance acquired beta-lactam resistance mechanisms in K.
      pneumoniae and have defined the envelope protein abundance changes upon RamA
      overproduction during growth in low and high osmolarity media. Methods: Envelope
      permeability was estimated using a fluorescent dye accumulation assay. beta
      Lactam susceptibility was measured using disc testing. Total envelope protein
      production was quantified using LC-MS/MS proteomics and transcript levels were
      quantified using real-time RT-PCR. Results: RamA overproduction enhanced beta
      lactamase-mediated beta-lactam resistance, in some cases dramatically, without
      altering beta-lactamase production. It increased production of efflux pumps and
      decreased OmpK35 porin production, though micF overexpression showed that OmpK35
      reduction has little impact on envelope permeability. A survey of K. pneumoniae
      bloodstream isolates revealed ramA hyperexpression in 3 of 4 carbapenemase
      producers, 1 of 21 CTX-M producers and 2 of 19 strains not carrying CTX-M or
      carbapenemases. Conclusions: Whilst RamA is not a key mediator of antibiotic
      resistance in K. pneumoniae on its own, it is potentially important for enhancing
      the spectrum of acquired beta-lactamase-mediated beta-lactam resistance. LC-MS/MS
      proteomics analysis has revealed that this enhancement is achieved predominantly
      through activation of efflux pump production.

PMID- 29029195
TI  - Helpfulness, Trust, and Safety of Neighborhoods: Social Capital, Household
      Income, and Self-Reported Health of Older Adults.
AB  - Background and Objectives: Growing literature documents that where you live has
      an impact on your health, due in part to social capital. Building on social
      capital literature, we assess how subjective appraisals of neighborhood quality
      are associated with self-reported health (SRH) for older adults. Research Design
      and Methods: Cross-sectional analysis of the 2014 California Health Interview
      Survey, a representative survey of diverse, noninstitutionalized California
      residents. We use three measures of neighborhood quality: trustworthy neighbors,
      helpful neighbors, and feeling safe. Using weighted ordinary least squares
      regression, we assess the associations of trust, helpfulness, and safety to SRH,
      controlling for neighborhood, demographic, and health care variables. We then
      examine how these associations vary by household income. Results: We find that
      characterizing neighbors as helpful and feeling safe are associated with better
      SRH, even controlling for community, demographic, and health care variables.
      However, the importance of these dimensions varies across household income:
      helpfulness is positively associated, whereas trust is negatively associated with
      SRH for lower income residents; safety is positively associated with SRH in all
      but the lowest income residents. These findings show that social capital
      dimensions work differently from one another, and differentially affect the
      health of older adults. Discussion and Implications: Scholarly analyses of
      neighborhood effects should include a range of social capital measures and
      stratify by household income. Our findings may also inform priority setting for
      social capital programs, especially for older adults with limited economic
      resources. Policies and programs should consider actions that raise perceptions
      of helpfulness and safety.

PMID- 29029197
TI  - Microsurgical Clip Reconstruction of a 1 cm Complex Anterior Communicating Artery
      Aneurysm via an Orbitozygomatic Approach: 2-Dimensional Operative Video.

PMID- 29029196
TI  - Association Between Coronary Artery Calcification and the Hemoglobin Glycation
      Index: The Kangbuk Samsung Health Study.
AB  - Context: The hemoglobin glycation index (HGI) is known to be correlated with the
      risk for cardiovascular disease. Objective: To analyze the association between
      incident coronary artery calcification (CAC) and the changes in HGI among
      participants without diabetes, over 4 years. Design, Setting, Participants, and
      Outcome Measures: A retrospective study of 2052 nondiabetic participants in whom
      the coronary artery calcium score was measured repeatedly over 4 years, as part
      of a health checkup program in Kangbuk Samsung Hospital in Korea, and who had no
      CAC at baseline. The HGI was defined as the difference between the measured and
      predicted hemoglobin A1c (HbA1c) levels. Results: A total of 201 participants
      developed CAC after 4 years, and the mean baseline HGI was significantly higher
      in those patients. The incidence of CAC gradually increased from the first to the
      fourth quartile groups of baseline HGI. The odds ratio (OR) for incident CAC was
      the highest among the four groups divided by the quartiles of the baseline HGI
      and was significant after adjustment for confounding variables (vs first quartile
      group: OR, 1.632; 95% confidence interval, 1.024 to 2.601). The incidence of and
      risk for CAC development were significantly higher than in other groups compared
      with the low-to-low group after adjustment for confounding factors; however, when
      baseline HbA1c level was included in the model, only participants with a low-to
      high HGI over 4 years showed a significantly increased OR for CAC development
      compared with the low-to-low group (OR, 1.722; 95% confidence interval, 1.046 to
      2.833). Conclusions: The participants with a high baseline HGI and consistently
      high HGI showed a higher risk for incident CAC than those with a low baseline
      HGI. An increased HGI over 4 years significantly increased the risk for CAC
      regardless of the baseline HbA1c levels.

PMID- 29029198
TI  - Different genomic changes underlie adaptive evolution in populations of
      contrasting history.
AB  - Experimental evolution is a powerful tool to understand the adaptive potential of
      populations under environmental change. Here, we study the importance of the
      historical genetic background in the outcome of evolution at the genome-wide
      level. Using the natural clinal variation of Drosophila subobscura, we sampled
      populations from two contrasting latitudes (Adraga, Portugal and Groningen,
      Netherlands) and introduced them in a new common environment in the laboratory.
      We characterized the genome-wide temporal changes underlying the evolutionary
      dynamics of these populations, which had previously shown fast convergence at the
      phenotypic level, but not at chromosomal inversion frequencies. We found that
      initially differentiated populations did not converge either at genome-wide level
      or at candidate SNPs with signs of selection. In contrast, populations from
      Portugal showed convergence to the control population that derived from the same
      geographical origin and had been long-established in the laboratory. Candidate
      SNPs showed a variety of different allele frequency change patterns across
      generations, indicative of an underlying polygenic basis. We did not detect
      strong linkage around candidate SNPs, but rather a small but long-ranging effect.
      In conclusion, we found that history played a major role in genomic variation and
      evolution, with initially differentiated populations reaching the same adaptive
      outcome through different genetic routes.

PMID- 29029199
TI  - A Surrogate Function for One-Dimensional Phylogenetic Likelihoods.
AB  - Phylogenetics has seen a steady increase in data set size and substitution model
      complexity, which require increasing amounts of computational power to compute
      likelihoods. This motivates strategies to approximate the likelihood functions
      for branch length optimization and Bayesian sampling. In this article, we develop
      an approximation to the 1D likelihood function as parametrized by a single branch
      length. Our method uses a four-parameter surrogate function abstracted from the
      simplest phylogenetic likelihood function, the binary symmetric model. We show
      that it offers a surrogate that can be fit over a variety of branch lengths, that
      it is applicable to a wide variety of models and trees, and that it can be used
      effectively as a proposal mechanism for Bayesian sampling. The method is
      implemented as a stand-alone open-source C library for calling from phylogenetics
      algorithms; it has proven essential for good performance of our online
      phylogenetic algorithm sts.

PMID- 29029200
TI  - Lateral Cerebellar Nucleus Stimulation has Selective Effects on Glutamatergic and
      GABAergic Perilesional Neurogenesis After Cortical Ischemia in the Rodent Model.
AB  - BACKGROUND: Chronic deep brain stimulation of the rodent lateral cerebellar
      nucleus (LCN) has been demonstrated to enhance motor recovery following cortical
      ischemia. This effect is concurrent with synaptogenesis and expression of long
      term potentiation markers in the perilesional cerebral cortex. OBJECTIVE: To
      further investigate the cellular changes associated with chronic LCN stimulation
      in the ischemic rodent by examining neurogenesis along the
      cerebellothalamocortical pathway. METHODS: Rats were trained on the pasta matrix
      task, followed by induction of cortical ischemia and electrode implantation in
      the contralesional LCN. Electrical stimulation was initiated 6 wk after stroke
      induction and continued for 4 wk prior to sacrifice. Neurogenesis was examined
      using immunohistochemistry. RESULTS: Treated animals showed enhanced performance
      on the pasta matrix task relative to sham controls. Increased cell proliferation
      colabeled with 5'-Bromo-2'-deoxyuridine and neurogenic markers (doublecortin) was
      observed in the perilesional cortex as well as bilateral mediodorsal and
      ventrolateral thalamic subnuclei in treated vs untreated animals. The neurogenic
      effect at the level of motor cortex was selective, with stimulation-treated
      animals showing greater glutamatergic neurogenesis but significantly less
      GABAergic neurogenesis. CONCLUSION: These findings suggest that LCN deep brain
      stimulation modulates postinjury neurogenesis, providing a possible mechanistic
      foundation for the associated enhancement in poststroke motor recovery.

PMID- 29029201
TI  - A Comprehensive Comparison of Quantifications of Intraindividual Variability in
      Response Times: A Measurement Burst Approach.
AB  - Objectives: To formally identify and contrast the most commonly-employed
      quantifications of response time inconsistency (RTI) and elucidate their utility
      for understanding within-person (WP) and between-person (BP) variation in
      cognitive function with increasing age. Method: Using two measurement burst
      studies of cognitive aging, we systematically identified and computed five RTI
      quantifications from select disciplines to examine: (a) correlations among RTI
      quantifications; (b) the distribution of BP and WP variation in RTI; and (c) the
      comparability of RTI quantifications for predicting attention switching. Results:
      Comparable patterns were observed across studies. There was significant variation
      in RTI BP as well as WP across sessions and bursts. Correlations among RTI
      quantifications were generally strong and positive both WP and BP, except for the
      coefficient of variation. Independent prediction models indicated that slower
      mean response time (RT) and greater RTI were associated with slower attention
      switching both WP and BP. For selecting simultaneous prediction models,
      collinearity resulted in inflated standard errors and unstable model estimates.
      Discussion: RTI reflects a novel dimension of performance that is a robust and
      theoretically informative predictor of BP and WP variation in cognitive function.
      Among the plenitude of RTI quantifications, not all are interchangeable, nor of
      comparable predictive utility.

PMID- 29029203
TI  - Prognostic significance of computed tomography criteria for pulmonary veno
      occlusive disease in systemic sclerosis-pulmonary arterial hypertension.
AB  - Objectives: SSc-pulmonary arterial hypertension (SSc-PAH) is associated with
      worse response to therapy and survival when compared with idiopathic PAH. It is
      suggested that the vasculopathy in SSc may involve postcapillary pulmonary
      venules resulting in pulmonary veno-occlusive disease (PVOD). This may underlie
      the lower gas transfer and worse outcome on therapy. We sought to test whether CT
      signs of PVOD (CTS-PVOD) were frequent in SSc-PAH and whether they were
      associated with pulmonary oedema on therapy and worse survival. Methods: CT
      thorax of 66 SSc patients with precapillary pulmonary hypertension (PH) were
      blindly scored by two radiologists for CTS-PVOD (?1 or ? 2). Case note and
      radiograph review determined the presence of pulmonary oedema on therapy.
      Results: Fifty-nine patients (89%) had ?1 CTS-PVOD and only 7 (11%) had ?2 CTS
      PVOD. Pulmonary oedema on therapy was relatively common in those with ?2 CTS
      PVOD. On univariate analysis ?2 CTS-PVOD were associated with a trend towards
      worse survival. Conclusion: CTS-PVOD were less frequent in this SSc-PAH cohort
      than in previous reports but the presence of at least two of these signs is
      associated with pulmonary oedema on therapy and a trend towards worse survival on
      univariate analysis.

PMID- 29029202
TI  - A Metabolomic Signature of Acute Caloric Restriction.
AB  - Context: The experimental paradigm of acute caloric restriction (CR) followed by
      refeeding (RF) can be used to study the homeostatic mechanisms that regulate
      energy homeostasis, which are relevant to understanding the adaptive response to
      weight loss. Objective: Metabolomics, the measurement of hundreds of small
      molecule metabolites, their precursors, derivatives, and degradation products,
      has emerged as a useful tool for the study of physiology and disease and was used
      here to study the metabolic response to acute CR. Participants, Design, and
      Setting: We used four ultra high-performance liquid chromatography-tandem mass
      spectrometry methods to characterize changes in carbohydrates, lipids, amino
      acids, and steroids in eight normal weight men at baseline, after 48 hours of CR
      (10% of energy requirements) and after 48 hours of ad libitum RF in a tightly
      controlled environment. Results: We identified a distinct metabolomic signature
      associated with acute CR characterized by the expected switch from carbohydrate
      to fat utilization with increased lipolysis and beta-fatty acid oxidation. We
      found an increase in omega-fatty acid oxidation and levels of endocannabinoids,
      which are known to promote food intake. These changes were reversed with RF.
      Several plasmalogen phosphatidylethanolamines (endogenous antioxidants)
      significantly decreased with CR (all P <= 0.0007). Additionally, acute CR was
      associated with an increase in the branched chain amino acids (all P <= 1.4 * 10
      7) and dehydroepiandrosterone sulfate (P = 0.0006). Conclusions: We identified a
      distinct metabolomic signature associated with acute CR. Further studies are
      needed to characterize the mechanisms that mediate these changes and their
      potential contribution to the adaptive response to dietary restriction.

PMID- 29029204
TI  - Evidence of Premating Isolation Between Two Sibling Moths: Ectropis grisescens
      and Ectropis obliqua (Lepidoptera: Geometridae).
AB  - The sex pheromones of Ectropis grisescens Warren and Ectropis obliqua Prout were
      both reported to contain (Z,Z,Z)-3,6,9-octadecatriene (Z3,Z6,Z9-18:H) and (Z,Z)
      3,9-cis-6,7-epoxy-octadecadiene (Z3,epo6,Z9-18:H). To clarify how these two
      sibling geometrids maintain premating isolation, the female sex pheromones of the
      two species were reexamined. Gas chromatography-electroantennographic detection
      (GC-EAD) and gas chromatography-mass spectrometry revealed two GC-EAD-active
      compounds, Z3,Z6,Z9-18:H and Z3,epo6,Z9-18:H, in E. grisescens female pheromone
      glands as well as an additional GC-EAD-active compound, (Z,Z)-3,9-cis-6,7-epoxy
      nonadecadiene (Z3,epo6,Z9-19:H), in E. obliqua female pheromone glands.
      Synthesized Z3,Z6,Z9-18:H and Z3,epo6,Z9-18:H elicited dose-dependent
      electroantennogram (EAG) responses from male antennae of both E. grisescens and
      E. obliqua. However, Z3,epo6,Z9-19:H only elicited dose-dependent EAG responses
      from E. obliqua and limited EAG responses from E. grisescens at all doses. In
      wind-tunnel studies, lures that contained Z3,Z6,Z9-18:H and Z3,epo6,Z9-18:H
      attracted E. grisescens males and had no effect on E. obliqua males. The addition
      of Z3,epo6,Z9-19:H to the blend of Z3,Z6,Z9-18:H and Z3,epo6,Z9-18:H strongly
      attracted E. obliqua males but had a limited attraction for E. grisescens males.
      Thus, Z3,Z6,Z9-18:H and Z3,epo6,Z9-18:H were sex pheromone components of E.
      grisescens, whereas Z3,Z6,Z9-18:H, Z3,epo6,Z9-18:H and Z3,epo6,Z9-19:H were sex
      pheromone components of E. obliqua. The presence or absence of Z3,epo6,Z9-19:H
      played a central role in the premating isolation of these two sibling species.

PMID- 29029205
TI  - Transcriptome Analysis of the Triatoma infestans (Hemiptera: Reduviidae)
      Integument.
AB  - The insect integument, formed by the cuticle and the underlying epidermis, is
      essential for insect fitness, regulation of lipid biosynthesis and storage,
      insect growth and feeding, together with development progress. Its participation
      in insecticide resistance has also been outlined. Triatoma infestans Klug
      (Hemiptera: Reduviidae) is one of the major vectors of Chagas disease in South
      America; however, genomic data are scarce. In this study, we performed a
      transcriptome analysis of the nymph integument in order to identify which genes
      are expressed and their putative role. Using the 454 GS-FLX sequencing platform,
      we obtained approximately 144,620 reads from the integument tissue. These reads
      were assembled into 6,495 isotigs and 8,504 singletons. Based on BLAST similarity
      searches, about 8,000 transcripts were annotated with known genes, conserved
      domains, and/or Gene Ontology terms.The most abundant transcripts corresponded to
      transcription factors and nucleic acid metabolism, membrane receptors, cell
      signaling, and proteins related to cytoskeleton, transport, and cell energy
      processes, among others. More than 10% of the transcripts-encoded proteins
      putatively involved in the metabolism of fatty acids and related components
      (fatty acid synthases, elongases, desaturases, fatty alcohol reductases),
      structural integument proteins, and the insecticide detoxification system (among
      them, cytochrome P450s, esterases, and glutathione transferases). Real-time qPCR
      assays were used to investigate their putative participation in the resistance
      mechanism. This preliminary study is the first transcriptome analysis of a
      triatomine integument, and together with prior biochemical information, will help
      further understandthe role of the integument in a wide array of mechanisms.

PMID- 29029208
TI  - Dust storms, heart attacks, and protecting those at risk.

PMID- 29029207
TI  - European Association of Preventive Cardiology (EAPC) and European Association of
      Cardiovascular Imaging (EACVI) joint position statement: recommendations for the
      indication and interpretation of cardiovascular imaging in the evaluation of the
      athlete's heart.

PMID- 29029206
TI  - Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T-Cell
      Decline, and Per-Parasite Pathogenicity.
AB  - Pathogen strains may differ in virulence because they attain different loads in
      their hosts, or because they induce different disease-causing mechanisms
      independent of their load. In evolutionary ecology, the latter is referred to as
      "per-parasite pathogenicity". Using viral load and CD4+ T-cell measures from 2014
      HIV-1 subtype B-infected individuals enrolled in the Swiss HIV Cohort Study, we
      investigated if virulence-measured as the rate of decline of CD4+ T cells-and per
      parasite pathogenicity are heritable from donor to recipient. We estimated
      heritability by donor-recipient regressions applied to 196 previously identified
      transmission pairs, and by phylogenetic mixed models applied to a phylogenetic
      tree inferred from HIV pol sequences. Regressing the CD4+ T-cell declines and per
      parasite pathogenicities of the transmission pairs did not yield heritability
      estimates significantly different from zero. With the phylogenetic mixed model,
      however, our best estimate for the heritability of the CD4+ T-cell decline is 17%
      (5-30%), and that of the per-parasite pathogenicity is 17% (4-29%). Further, we
      confirm that the set-point viral load is heritable, and estimate a heritability
      of 29% (12-46%). Interestingly, the pattern of evolution of all these traits
      differs significantly from neutrality, and is most consistent with stabilizing
      selection for the set-point viral load, and with directional selection for the
      CD4+ T-cell decline and the per-parasite pathogenicity. Our analysis shows that
      the viral genotype affects virulence mainly by modulating the per-parasite
      pathogenicity, while the indirect effect via the set-point viral load is minor.

PMID- 29029209
TI  - Genetic Evidence for the Introduction of Rhagoletis pomonella (Diptera:
      Tephritidae) into the Northwestern United States.
AB  - The apple maggot fly, Rhagoletis pomonella Walsh (Diptera: Tephritidae), is a
      serious quarantine pest in the apple-growing regions of central Washington and
      Oregon. The fly is believed to have been introduced into the Pacific Northwest
      via the transport of larval-infested apples near Portland, Oregon, within the
      last 40 yr. However, R. pomonella also attacks native black hawthorn, Crataegus
      douglasii Lindley (Rosales: Rosaceae), and introduced ornamental hawthorn,
      Crataegus monogyna Jacquin, in the region. It is, therefore, possible that R.
      pomonella was not introduced but has always been present on black hawthorn. If
      true, then the fly may have independently shifted from hawthorn onto apple in the
      Pacific Northwest within the last 40 yr after apples were introduced. Here, we
      test the introduction hypothesis through a microsatellite genetic survey of 10 R.
      pomonella sites in Washington and 5 in the eastern United States, as well as a
      comparison to patterns of genetic variation between populations of Rhagoletis
      cingulata Loew and Rhagoletis indifferens Curran, two sister species of cherry
      infesting flies known to be native to the eastern and western United States,
      respectively. We report results based on genetic distance networks, patterns of
      allelic variation, and estimated times of population divergence that are
      consistent with the introduction hypothesis for R. pomonella. The results have
      important implications for R. pomonella management, suggesting that black
      hawthorn-infesting flies near commercial apple-growing regions of central
      Washington may harbor sufficient variation to utilize apple as an alternate host,
      urging careful monitoring, and possible removal of hawthorn trees near orchards.

PMID- 29029211
TI  - What is value health care and who is the judge?

PMID- 29029210
TI  - Lesinurad monotherapy in gout patients intolerant to a xanthine oxidase
      inhibitor: a 6 month phase 3 clinical trial and extension study.
AB  - Objective: To investigate the efficacy and safety of lesinurad, a selective uric
      acid reabsorption inhibitor, in a 6 month, phase 3 clinical trial and extension
      study. Methods: Patients with gout who cannot take a xanthine oxidase inhibitor
      (XOI) and have serum uric acid (sUA) ?6.5 mg/dl were randomized to receive oral
      lesinurad (400 mg daily) or placebo. The primary endpoint was the proportion of
      patients with sUA <6.0 mg/dl at month 6. Safety assessments included treatment
      emergent adverse events (TEAEs) and laboratory data. Patients who completed the
      study were eligible for an open-label, uncontrolled extension study of lesinurad
      400 mg monotherapy. Results: Patients (n = 214) were primarily white males (mean
      age 54.4 years; gout duration 11.2 years). Significantly more patients achieved
      the primary endpoint with lesinurad than placebo (29.9 vs 1.9%; P < 0.0001).
      Overall TEAE rates were higher with lesinurad (77.6 vs 65.4%); renal-related
      TEAEs (17.8%), renal-related serious TEAEs (4.7%) and serum creatinine elevations
      (1.5 times baseline, 24.3%) occurred only with lesinurad. A total of 143 patients
      (65 lesinurad, 78 placebo) enrolled in the extension study. Treatment with
      lesinurad 400 mg resulted in rapid and sustained sUA lowering that persisted for
      up to 18 months before the study was terminated prematurely. No new safety
      findings were observed in the extension. Conclusion: In patients with gout and
      intolerance/contraindication to XOIs, lesinurad 400 mg monotherapy demonstrated
      superior sUA lowering compared with placebo, with sustained effects for up to 18
      months. Due to a high incidence of serum creatinine elevations and renal-related
      adverse events, including serious adverse events with lesinurad 400 mg, lesinurad
      should not be used as monotherapy. Trial registration: ClinicalTrials.gov
      (http://clinincaltrials.gov), NCT01508702.

PMID- 29029212
TI  - Galaxy sign in alveolar sarcoidosis: An unusual radiological presentation of
      Lofgren's syndrome.

PMID- 29029213
TI  - Recovery Kinetics of Radiographic and Implant-Related Revision Patients Following
      Adult Spinal Deformity Surgery.
AB  - BACKGROUND: Prior studies have observed similar health-related quality of life
      (HRQL) in revisions and nonrevision (NR) patients following adult spinal
      deformity (ASD) correction. However, a novel comparison approach may allow better
      comparisons in spine outcomes groups. OBJECTIVE: To determine if ASD revisions
      for radiographic and implant-related complications undergo a different recovery
      than NR patients. METHODS: Inclusion: ASD patients with complete HRQL (Oswestry
      Disability Index, Short-Form-36 version 2 (SF-36), Scoliosis Research Society
      [SRS]-22) at baseline, 6 wk, 1 yr, 2 yr. Generated revision groups: nonrevision
      (NR), revised-complete data (RC; with follow-up 2 yr after revision), and revised
      incomplete data (RI; without 2-yr follow-up after revision). In a traditional
      analysis, analysis of variance (ANOVA) compared baseline HRQLs to follow-up
      changes. In a novel approach, integrated health state was normalized at baseline
      using area under curve analysis before ANOVA t-tests compared follow-up statuses.
      RESULTS: Two hundred fifty-eight patients were included with 50 undergoing
      reoperations (19.4%). Rod fractures (n = 15) and proximal joint kyphosis (n = 9)
      were most common. In standard HRQL analysis, comparing RC index surgery and RC
      revision surgery HRQLS revealed no significant differences throughout the 2-yr
      follow-up from either the initial index or revision procedure. Using normalized
      HRQL/integrated health state, RI displayed worse scores in SF-36 Physical
      Component Score, SRS activity, and SRS appearance relative to NR (P < .05),
      indicating less improvement over the 2-yr period. RC were significantly worse
      than RI in SF-36 Mental Component Score, SRS mental, SRS satisfaction, and SRS
      total (P < .05). CONCLUSION: ASD patients indicated for revisions for
      radiographic and implant-related complications differ significantly in their
      overall 2-yr recovery compared to NR, using a normalized integrated health state
      method. Traditional methods for analyzing revision patients' recovery kinetics
      may overlook delayed improvements.

PMID- 29029215
TI  - Child Sexual Abuse and Depression in Late Life for Men: A Population-Based,
      Longitudinal Analysis.
AB  - Objective: Research investigating long-term effects of childhood sexual abuse
      (CSA) on mental health for men is vastly underdeveloped. This study strengthened
      the knowledge base by examining: (a) long-term trajectories of depressive
      symptoms for men with and without a history of CSA, and (b) moderating effects of
      social support over time. Method: We analyzed multiple waves of data from the
      Wisconsin Longitudinal Study. The sample (N = 2,451) consisted of men with
      histories of CSA and a stratified, randomly sampled comparison group. Growth
      curve modeling was employed for analyses. Results: After controlling for
      demographic, parental, and health factors, men with CSA histories had greater
      depressive symptoms than those with no history of CSA. For both groups,
      depressive symptoms decreased over time; slope patterns did not differ. We found
      a significant moderating effect of social support on the relationship between CSA
      and depressive symptoms. Discussion: This innovative, population-based,
      longitudinal study demonstrated that CSA can undermine mental health for men
      across the life span and into old age. Social support appears to mitigate these
      deleterious effects. In early, middle, and late adulthood, practitioners should
      assess for CSA and strengthen support resources for male survivors.

PMID- 29029214
TI  - Sleepless Night and Day, the Plight of Progressive Supranuclear Palsy.
AB  - Objectives: To elucidate the unique sleep and waking characteristics in
      progressive supranuclear palsy (PSP), a neurodegenerative disease associated with
      motor deficits and dementia that largely affects the brainstem and thalamic
      regions. Methods: A total of 20 PSP and 16 healthy older adult controls
      participated in this study. The participants underwent an overnight
      polysomnography and multiple sleep latency test (MSLT) the following day. Prior
      to the MSLT last trial, they were asked to complete the Stanford Sleepiness
      Scale. Data were assessed for measures of latency to sleep onset, sleep duration,
      waking, and sleep staging during the night. Mean sleep latency, a measure of
      daytime sleepiness, sleep onset rapid eye movement (REM) periods, and microsleeps
      were studied with the MSLT. Spectral analysis of wake electroencephalogram (EEG)
      was performed for 30-second periods at the start of each MSLT trial. Results: PSP
      took significantly longer time to fall asleep (p < .001), slept less during the
      night (p <= .001), and had more wake after sleep onset than controls (p <= .001).
      PSP had less N2 sleep (p < .05) and N3 sleep (p < .05), and REM sleep (p < .001)
      than controls. During the MSLT, PSP took significantly longer to fall asleep (p <
      .001), did not have microsleeps when they remained awake throughout the
      assessment periods, but were subjectively sleepier than controls (p < .05). Gamma
      power was increased during wake EEG in PSP (p < .01). Conclusions: Sleep/waking
      regulation and REM sleep regulation are disrupted in PSP, leading to profound
      sleep deprivation without recuperation. Our findings suggest a diminished
      homeostatic sleep drive in PSP. This hyperaroused state is unique and is a
      severely disabling feature of PSP.

PMID- 29029216
TI  - Diversity and Distribution of Cryptic Species of the Bemisia tabaci (Hemiptera:
      Aleyrodidae) complex in Pakistan.
AB  - Bemisia tabaci (Gennadius; Hempitera: Aleyrodidae) is considered to be a cryptic
      (sibling) species complex, the members of which exhibit morphological
      invariability while being genetically and behaviorally distinct. Members of the
      complex are agricultural pests that cause direct damage by feeding on plants, and
      indirectly by transmitting viruses that cause diseases leading to reduced crop
      yield and quality. In Pakistan, cotton leaf curl disease, caused by multiple
      begomovirus species, is the most economically important viral disease of cotton.
      In the study outlined here, the diversity and geographic distribution of B.
      tabaci cryptic species was investigated by analyzing a taxonomically informative
      fragment of the mitochondrial cytochrome c oxidase 1 gene (mtCOI-3'). The mtCOI
      3' sequence was determined for 285 adult whiteflies and found to represent six
      cryptic species, the most numerous being Asia II-1 and Middle East Asia Minor 1
      (MEAM-1), the later also referred to as the B-biotype, which was previously
      thought to be confined to Sindh province but herein, was also found to be present
      in the Punjab province. The endemic Asia I was restricted to Sindh province,
      while an individual in the Asia II-8 was identified in Pakistan for the first
      time. Also for the first time, samples were collected from northwestern Pakistan
      and Asia II-1 was identified. Results indicate that in Pakistan the overall
      diversity of B. tabaci cryptic species is high and, based on comparisons with
      findings from previous studies, the distribution is dynamic.

PMID- 29029217
TI  - High levels of susceptibility to new and older antibiotics in Neisseria
      gonorrhoeae isolates from Saskatchewan (2003-15): time to consider point-of-care
      or molecular testing for precision treatment?
AB  - Objectives: The antimicrobial susceptibility of Neisseria gonorrhoeae isolates
      from Saskatchewan was determined retrospectively (2003-15) to ascertain temporal
      trends to both current and older antimicrobials used for treatment. Method: The
      agar dilution method was used to test the antimicrobial susceptibilities of 685
      isolates to seven antibiotics. Results: Over the period, only three (0.4%)
      gonococcal isolates had reduced susceptibility to cefixime and/or ceftriaxone.
      All isolates were susceptible to spectinomycin. Over 95% of the isolates tested
      were susceptible to azithromycin except in 2010 and 2013 (27.6% and 7.2%
      resistant, respectively). One isolate was resistant to both azithromycin and
      cefixime. Ciprofloxacin resistance was seen in < 5% of isolates prior to 2010,
      but in > 5% thereafter. From 2006 to 2012, and in 2015, penicillin resistance was
      detected in < 5% (0%-4.0%) of isolates, but in > 5% for the rest of the study
      period. Tetracycline resistance remained >5% (11.8%-89.1%) throughout the study.
      Plasmid-mediated resistance to tetracycline fluctuated between 0% and 17.5% of
      isolates tested. Four isolates were MDR and two isolates were XDR. Conclusions:
      N. gonorrhoeae isolates were largely susceptible (~85%) to antibiotics no longer
      recommended for treatment, such as penicillin and ciprofloxacin. Gonorrhoea in
      Saskatchewan is primarily (>95%) diagnosed by nucleic acid amplification testing,
      which does not permit antimicrobial susceptibility testing. The development of
      molecular testing, or point-of-care tests, to evaluate antimicrobial
      susceptibility, would enhance knowledge of true levels of resistance and allow
      discretion as to whether older but still effective antibiotics could be used in
      individual patient care.

PMID- 29029218
TI  - Dose-Dependent Effects on Replication and Persistence of Salmonella enterica
      serovar Typhimurium in House Flies (Diptera: Muscidae).
AB  - Adult house flies (Musca domestica L.) ingest variable numbers of bacteria when
      they encounter microbe-rich substrates. Bacterial abundance may affect
      replication within the fly gut, which subsequently impacts vector potential. This
      study investigated the dose-dependent replication of GFP-expressing Salmonella
      enterica serovar Typhimurium (ex Kauffmann and Edwards1952) Le Minor and Popoff
      1987, (Enterobacteriales: Enterobacteriaceae) (GFP S. Typhimurium) within the fly
      alimentary canal. Adult house flies were fed two doses (colony forming units,
      CFU) of GFP S. Typhimurium (high, ~105 CFU and low, ~104 CFU). Bacteria were
      examined at 2-, 4-, 6-, 12-, and 24-h postingestion (PI) in situ in the gut via
      epifluorescence microscopy and enumerated by culture on selective media. In both
      treatment groups, GFP S. Typhimurium proliferated and persisted in flies for 24
      h. In the high-dose group, proliferation peaked at 6 h PI (>500% increase). In
      the low-dose group, proliferation peaked at both 4 and 6 h PI (>900% increase).
      Dose significantly affected bacterial replication within the house fly alimentary
      canal, particularly at 4-, 6-, and 12-h PI. The ability of S. Typhimurium to
      proliferate and persist in the alimentary canal demonstrates that house flies may
      serve as significant reservoirs and probable disseminators of this pathogen. Our
      results show that bacterial abundance should be considered when assessing the
      potential of house flies to harbor and transmit pathogens.

PMID- 29029219
TI  - Pupation Behavior and Predation on Drosophila suzukii (Diptera: Drosophilidae)
      Pupae in Maine Wild Blueberry Fields.
AB  - Drosophila suzukii (Matsumura; Diptera: Drosophilidae) is an invasive vinegar fly
      and pest of soft fruits in North America, including wild blueberries (Vaccinium
      angustifolium Aiton) in Maine. Despite its presence in the continental United
      States for 9 yr, little is known about its natural enemy complex. Here we report
      the results of a 3-yr study designed to identify naturally-occurring predators in
      Maine's wild blueberry fields. Experiments were conducted to determine pupation
      site and pupation depth to understand D. suzukii's predation vulnerability.
      Predation rates in the field of fully-exposed, caged, and buried pupae were
      measured. Pitfall traps were deployed to identify the potential predator
      assemblage, and laboratory experiments were conducted to determine how many pupae
      were consumed by commonly occurring ground beetle species (Carabidae) and field
      crickets (Gryllus pennsylvanicus Burmeister). The most commonly collected
      predators were ants, ground beetles, harvestmen, and field crickets.
      Significantly more pupae were found to occur in the soil compared to blueberry
      fruit, with most pupae in the top 0.5 cm layer of soil. Pupal predation rates in
      the field were high, with higher rates of predation on exposed pupae compared to
      buried pupae. Laboratory studies revealed that ground beetles and field crickets
      are likely predators of D. suzukii pupae.

PMID- 29029220
TI  - Effects of host traits and land-use changes on the gut microbiota of the Namibian
      black-backed jackal (Canis mesomelas).
AB  - Host traits and environmental factors drive the natural variation in gut
      microbiota, and disruption in homeostasis can cause infections and chronic
      diseases. African wildlife is increasingly facing human-induced agricultural
      habitats, which also amplifies the contact probability with livestock with
      unknown consequences for wildlife gut microbiotas and the risk of transmission of
      potentially pathogenic bacteria. We applied high-throughput sequencing of
      bacterial 16S rRNA genes and microsatellite genotyping to investigate the impact
      of host traits and habitat use on the gut microbiotas of black-backed jackals
      (Canis mesomelas). This abundant carnivore inhabits livestock and game farms in
      central Namibia and is often persecuted as pathogen reservoir and vector. We
      further compared the gut microbiotas of black-backed jackals to other wild and
      domestic carnivores, herbivores and an omnivore, to disentangle the effects of
      environment, host species and dietary preference. In black-backed jackals,
      intrinsic host traits had a stronger impact in shaping the host-bacteria
      relationship than environmental factors. Nevertheless, the abundance of bacterial
      operational taxonomic units (OTUs) differed in individuals from livestock and
      game farms for specific bacterial genera such as Lactobacillus and Clostridium.
      We found, however, no evidence that black-backed jackals harbour abnormal levels
      of OTUs related to potential bacterial pathogens or that livestock farming has a
      negative impact on their health. We present here the first study investigating
      simultaneously the impact of host traits and environmental factors on gut
      microbiotas of a wildlife carnivore that occurs in a human-modified habitat.

PMID- 29029222
TI  - The Scarring Effects of Father's Unemployment? Job-Security Satisfaction and
      Mental Health at Midlife.
AB  - Objectives: We investigate the association between early-life paternal
      unemployment and midlife mental health, examining whether the impact of father's
      unemployment may vary contingent on the broader economic context on which it
      occurred. We also investigate job-security satisfaction as a potential mediator
      of this association. Method: We utilize random-effects models, drawing on 15
      waves of data from the Household, Income and Labour Dynamics in Australia (HILDA)
      Survey, with 7,438 individuals and 42,309 individual-time observations. Results:
      We find respondents whose father was unemployed report worse mental health at
      midlife (-2.27; p < .01), with the association being modest, though statistically
      significant. This association is also stronger for younger respondents, whose
      paternal unemployment was more likely during the economic downturn of the mid
      1970s in Australia. Paternal unemployment is also associated with lower
      satisfaction with job security at midlife (-0.17; p < 0.05), which is related to
      worse mental health; however, it explains little of the association between
      paternal unemployment and mental health. Discussion: Existing research finds
      paternal unemployment relates to educational attainment, socioeconomic
      achievement, and wellbeing in the shorter term, but exposure to this event may
      also have enduring implications for the wellbeing of the offspring.

PMID- 29029221
TI  - Analysis of Clostridium difficile biofilms: imaging and antimicrobial treatment.
AB  - Background: Clostridium difficile, a spore-forming Gram-positive anaerobic
      bacillus, is the most common causative agent of healthcare-associated diarrhoea.
      Formation of biofilms may protect C. difficile against antibiotics, potentially
      leading to treatment failure. Furthermore, bacterial spores or vegetative cells
      may linger in biofilms in the gut causing C. difficile infection recurrence.
      Objectives: In this study, we evaluated and compared the efficacy of four
      antibiotics (fidaxomicin, surotomycin, vancomycin and metronidazole) in
      penetrating C. difficile biofilms and killing vegetative cells. Methods: C.
      difficile biofilms grown initially for 48 or 72 h using the colony biofilm model
      were then treated with antibiotics at a concentration of 25 * MIC for 24 h.
      Vegetative cells and spores were enumerated. The effect of treatment on biofilm
      structure was studied by scanning electron microscopy (SEM). The ability of
      fidaxomicin and surotomycin to penetrate biofilms was studied using fluorescently
      tagged antibiotics. Results: Both surotomycin and fidaxomicin were significantly
      more effective than vancomycin or metronidazole (P < 0.001) at killing vegetative
      cells in established biofilms. Fidaxomicin was more effective than metronidazole
      at reducing viable spore counts in biofilms (P < 0.05). Fluorescently labelled
      surotomycin and fidaxomicin penetrated C. difficile biofilms in < 1 h. After 24 h
      of treatment, SEM demonstrated that both fidaxomicin and surotomycin disrupted
      the biofilm structure, while metronidazole had no observable effect. Conclusions:
      Fidaxomicin is effective in disrupting C. difficile biofilms, killing vegetative
      cells and decreasing spore counts.

PMID- 29029223
TI  - Age and the Factor Structure of Emotional Experience in Adulthood.
AB  - Objectives: The current study examined the factor structure of emotional
      experience across adults 34-50, 51-65, and 66-84 year olds. Method: Participants
      (N = 2,022) were asked about 14 negative and 13 positive emotions across 8 days
      in the National Study of Daily Experiences II study. Factor analysis computed
      both inter-individual factors (between-person structure of emotional experience)
      and intra-individual factors (factors describing emotions in daily life) for each
      age group. Results: For inter-individual variation, one positive and one negative
      factor captured emotions experienced for the first two age groups, but the 66 to
      84-year-old adults had an additional factor for anger. For intra-individual
      variation, two factors (fear and sadness; anger) captured negative emotions for
      the first two age groups. The oldest age group had three negative factors: fear;
      anger (with additional sadness emotions); and sadness. Four factors captured
      positive emotions for the middle-aged groups and three for the oldest group;
      interpersonally oriented emotions (e.g. sense of belonging) were the primary
      sources of age differences. Discussion: Findings suggest that subtle age
      differences exist in the factor structure of daily emotional experience when
      comparing middle-aged and older adults.

PMID- 29029224
TI  - Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Vaccine
      Coadministered With Seasonal Influenza Vaccine in Adults Aged 50 Years or Older.
AB  - Background: The immunogenicity and safety of an adjuvanted herpes zoster subunit
      (HZ/su) vaccine when coadministered with a quadrivalent seasonal inactivated
      influenza vaccine (IIV4) was investigated in a phase 3, open-label, randomized
      clinical trial in adults aged >=50 years. Methods: Subjects were randomized 1:1
      to receive either HZ/su (varicella zoster virus glycoprotein E; AS01B Adjuvant
      System) and IIV4 at day 0 followed by a second HZ/su dose at month 2
      (coadministration group), or IIV4 at month 0 and HZ/su at months 2 and 4 (control
      group). The primary objectives were the HZ/su vaccine response rate in the
      coadministration group and the noninferiority of the antibody responses to HZ/su
      and IIV4 in the coadministration compared with the control group. Safety
      information was collected throughout the duration of the study. Results: A total
      of 413 subjects were vaccinated in the coadministration group and 415 in the
      control group. The HZ/su vaccine response rate in the coadministration group was
      95.8% (95% confidence interval, 93.3%-97.6%) and the anti-glycoprotein E
      GMCControl/Coadmin ratio was 1.08 (.97-1.20). The primary noninferiority
      objectives were met. No safety concerns were observed. Conclusions: No
      interference in the immune responses to either vaccine was observed when the
      vaccines were coadministered, and no safety concerns were identified. Clinical
      Trials Registration: NCT01954251.

PMID- 29029227
TI  - Local Versus Global Enterovirus (EV) Surveillance: A Discussion for the Need for
      Active Surveillance to Guide EV-A71 Vaccines.

PMID- 29029229
TI  - Implementing National HIV/AIDS Strategy 2015 Treatment Targets Is Cost-effective
      and Would Save Lives: What Other Evidence Do We Need?

PMID- 29029225
TI  - Glucocorticoid Signaling in Health and Disease: Insights From Tissue-Specific GR
      Knockout Mice.
AB  - Glucocorticoids are adrenally produced hormones critically involved in
      development, general physiology, and control of inflammation. Since their
      discovery, glucocorticoids have been widely used to treat a variety of
      inflammatory conditions. However, high doses or prolonged use leads to a number
      of side effects throughout the body, which preclude their clinical utility. The
      primary actions of glucocorticoids are mediated by the glucocorticoid receptor
      (GR), a transcription factor that regulates many complex signaling pathways.
      Although GR is nearly ubiquitous throughout the body, glucocorticoids exhibit
      cell- and tissue-specific effects. For example, glucocorticoids stimulate glucose
      production in the liver, reduce glucose uptake in the skeletal muscle, and
      decrease insulin secretion from the pancreatic beta-cells. Mouse models represent
      an important approach to understanding the dynamic functions of GR signaling in
      normal physiology, disease, and resistance. In the absence of a viable GR null
      model, gene-targeting techniques utilizing promoter-driven recombination have
      provided an opportunity to characterize the tissue-specific actions of GR. The
      aim of the present review is to describe the organ systems in which GR has been
      conditionally deleted and summarize the functions ascribed to glucocorticoid
      action in those tissues.

PMID- 29029228
TI  - Development of a Whole-Task Simulator for Carotid Endarterectomy.
AB  - BACKGROUND: Surgical education relies on operative exposure with live patients.
      Carotid endarterectomy (CEA) demands an experienced surgeon with a very low
      complication rate. The high-risk nature of this procedure and the decline in
      number of CEAs performed annually has created a gap in residency training.
      OBJECTIVE: To develop a high-fidelity whole-task simulation for CEA that
      demonstrates content, construct, and face validity. METHODS: Anatomically
      accurate models of the human neck were created using multilayered poly-vinyl
      alcohol hydrogels. Graded polymerization of the hydrogel was achieved by inducing
      crosslinks during freeze/thaw cycles, stiffening the simulated tissues to achieve
      realistic tactile properties. Venous bleeding was simulated using pressure bags
      and a ventricular assistive device created pulsatile flow in the carotid. Ten
      surgeons performed the simulation under operating room conditions, and metrics
      were compared among experience levels to determine construct validity.
      Participants completed surveys about realism and usefulness to evaluate face
      validity. RESULTS: A significant difference was found in operative measures
      between attending and resident physicians. The mean operative time for the expert
      group was 63.6 min vs 138.8 for the resident group (P = .002). There was a
      difference in mean internal carotid artery clamp time of 43.4 vs 83.2 min (P =
      .04). There were only 2 hypoglossal nerve injuries, both in the resident group (P
      = .009). CONCLUSION: The whole-task CEA simulator is a realistic, inexpensive
      model that offers comprehensive training and allows residents to master skills
      prior to operating on live patients. Overall, the model demonstrated face and
      construct validity among neurosurgery and vascular surgeons.

PMID- 29029230
TI  - Microbial organic acid production as carbon dioxide sink.
AB  - Mixed-substrate conversions are an under-regarded option to fix carbon dioxide in
      significant amounts. In such a conversion, carbon dioxide together with one other
      carbon source such as glucose is converted to a single carbon product. With mixed
      substrate conversions, it is possible to incorporate carbon dioxide into products
      with higher oxidation states than the co-substrate. Using abundant co-substrates
      such as glucose, glycerol or methanol, it is possible to produce organic acids
      anaerobically, using CO 2 both as an electron acceptor and as an additional
      carbon source. Here, we outline the thermodynamic feasibility to produce
      industrially important organic acids with this approach to provide guidance for
      future metabolic engineering endeavours.

PMID- 29029226
TI  - New Insights into the Genetic Basis of Monge's Disease and Adaptation to High
      Altitude.
AB  - Human high-altitude (HA) adaptation or mal-adaptation is explored to understand
      the physiology, pathophysiology, and molecular mechanisms that underlie long-term
      exposure to hypoxia. Here, we report the results of an analysis of the largest
      whole-genome-sequencing of Chronic Mountain Sickness (CMS) and nonCMS
      individuals, identified candidate genes and functionally validated these
      candidates in a genetic model system (Drosophila). We used PreCIOSS algorithm
      that uses Haplotype Allele Frequency score to separate haplotypes carrying the
      favored allele from the noncarriers and accordingly, prioritize genes associated
      with the CMS or nonCMS phenotype. Haplotypes in eleven candidate regions, with
      SNPs mostly in nonexonic regions, were significantly different between CMS and
      nonCMS subjects. Closer examination of individual genes in these regions revealed
      the involvement of previously identified candidates (e.g., SENP1) and also
      unreported ones SGK3, COPS5, PRDM1, and IFT122 in CMS. Remarkably, in addition to
      genes like SENP1, SGK3, and COPS5 which are HIF-dependent, our study reveals for
      the first time HIF-independent gene PRDM1, indicating an involvement of wider,
      nonHIF pathways in HA adaptation. Finally, we observed that down-regulating
      orthologs of these genes in Drosophila significantly enhanced their hypoxia
      tolerance. Taken together, the PreCIOSS algorithm, applied on a large number of
      genomes, identifies the involvement of both new and previously reported genes in
      selection sweeps, highlighting the involvement of multiple hypoxia response
      systems. Since the overwhelming majority of SNPs are in nonexonic (and possibly
      regulatory) regions, we speculate that adaptation to HA necessitates greater
      genetic flexibility allowing for transcript variability in response to graded
      levels of hypoxia.

PMID- 29029231
TI  - Analysis of Phylogenomic Tree Space Resolves Relationships Among Marsupial
      Families.
AB  - A fundamental challenge in resolving evolutionary relationships across the tree
      of life is to account for heterogeneity in the evolutionary signal across loci.
      Studies of marsupial mammals have demonstrated that this heterogeneity can be
      substantial, leaving considerable uncertainty in the evolutionary timescale and
      relationships within the group. Using simulations and a new phylogenomic data set
      comprising nucleotide sequences of 1550 loci from 18 of the 22 extant marsupial
      families, we demonstrate the power of a method for identifying clusters of loci
      that support different phylogenetic trees. We find two distinct clusters of loci,
      each providing an estimate of the species tree that matches previously proposed
      resolutions of the marsupial phylogeny. We also identify a well-supported
      placement for the enigmatic marsupial moles (Notoryctes) that contradicts
      previous molecular estimates but is consistent with morphological evidence. The
      pattern of gene-tree variation across tree-space is characterized by changes in
      information content, GC content, substitution-model adequacy, and signatures of
      purifying selection in the data. In a simulation study, we show that incomplete
      lineage sorting can explain the division of loci into the two tree-topology
      clusters, as found in our phylogenomic analysis of marsupials. We also
      demonstrate the potential benefits of minimizing uncertainty from phylogenetic
      conflict for molecular dating. Our analyses reveal that Australasian marsupials
      appeared in the early Paleocene, whereas the diversification of present-day
      families occurred primarily during the late Eocene and early Oligocene. Our
      methods provide an intuitive framework for improving the accuracy and precision
      of phylogenetic inference and molecular dating using genome-scale data.

PMID- 29029232
TI  - Immune checkpoint inhibitor-induced myo-fasciitis.

PMID- 29029233
TI  - Anticoagulation combined with antiplatelet therapy in patients with left
      ventricular thrombus after first acute myocardial infarction.
AB  - Aims: There are limited data about the optimal anti-thrombotic therapy for
      preventing embolism while minimizing bleeding events in patients with first acute
      myocardial infarction (AMI) complicated by left ventricular thrombus (LVT).
      Methods and results: Among 2301 consecutive patients with AMI hospitalized
      between 2001 and 2014, we studied 1850 patients with first AMI who discharged
      alive to investigate clinical characteristics, incidence of systemic embolism
      (SE), and association between anticoagulation and embolic or bleeding events.
      Left ventricular thrombus was diagnosed by echocardiography, left
      ventriculography, or cardiac magnetic resonance imaging in 92 (5.0%) patients (62
      +/- 12 years). During a median follow-up period of 5.4 years (interquartile range
      2.1-9.1 years), SE occurred in 15 of 92 patients with LVT (16.3%) and 51 of 1758
      patients without LVT (2.9%), respectively. Kaplan-Meier analysis showed a
      significantly higher incidence of SE in the LVT group (log-rank test, P < 0.001).
      Multivariate analysis showed that LVT was an independent predictor of SE. Among
      the LVT patients treated with vitamin K antagonists (n = 84), we compared the
      patients with therapeutic range (TTR) >=50% (n = 34) and those with TTR <50% (n =
      50). Only one embolic event developed in the TTR >=50% group and nine embolic
      events developed in the TTR <50% group (2.9% vs. 19%, P = 0.036). There was no
      difference in major bleeding events (TTR >=50%; 9% vs. TTR <50%; 8%, P = 0.89).
      Conclusion: Appropriate anticoagulation therapy may decrease the incidence of
      embolic events without increasing the incidence of bleeding events in patients
      with first AMI complicated by LV thrombus.

PMID- 29029234
TI  - Keeping education fresh-not just in microbiology.
AB  - Innovative practice from around the globe, addressing a range of recent
      educational themes and trends, was published in the FEMS Microbiology Letters
      virtual Thematic Issue 'Keeping Education Fresh' in October 2017. Its thought
      provoking content is reviewed here to more directly facilitate reflections and
      discussions in the professional community. The focus is on best practice
      approaches when enhancing student engagement, how to adjust those to the
      diversity of learners, learning situations and infrastructures, and to a broad
      range of subjects. The need for authentic learning and to move away from didactic
      teaching is emphasized. The 'students as researchers' theme is featured e.g. in
      context of service learning. Creative approaches are presented such as using
      performing arts, popular culture and gamification. The development of
      interdisciplinary and intercultural competences, and the exploration of
      socioscientific themes and philosophical issues are considered. Revisions of
      curricula and programmes, reflective of educational advancements and sector
      drivers, are discussed from undergraduate to postgraduate and professional
      specialist level also in light of problem-based learning, interactive distance
      and on-campus learning, and even the legacy of Massive Open Online Courses. Such
      changes always require resources and skills, and carry risks. Yet, innovation is
      a risk worth taking to keep education fresh.

PMID- 29029235
TI  - Predicting Nut Damage at Harvest Using Different in-Season Density Estimates of
      Amyelois Transitella: Analysis of Data from Commercial Almond Production.
AB  - Despite decades of research on management tactics for the navel orangeworm,
      Amyelois transitella (Walker) (Lepidoptera: Pyralidae), on almonds, we still do
      not have an established means of using in-season pest-density estimates to
      predict damage to nuts at harvest. As a result, hull-split pesticide
      applications, although timed carefully to coincide with navel orangeworm
      oviposition and with crop vulnerability, are not tied to pest densities-thus
      falling short of our goals under modern pest management. Here we use an
      ecoinformatics approach, analyzing a pre-existing data set collected in
      commercial almond production in California, to ask: 1) are navel orangeworm
      density estimates obtained using different sampling methods in strong agreement
      with one another? and 2) can we use either single density estimates or
      combinations of density estimates to explain variation in nutmeat damage at
      harvest? We find that correlations between density estimates of navel orangeworm
      made over a single growing season are often weak, and suggest that density
      estimates taken closer to the time of harvest (catches of adult females between
      hull split and harvest; infestation of early-split nuts) may be most useful for
      predicting damage at harvest. Single-density estimates explained <=39.1% of
      variation in harvest damage, whereas a combination of predictors explained 51.5%
      of the total variance in nutmeat damage at harvest. Our results suggest that
      density estimates taken just prior to harvest may, with refinement, be usable
      within a predictive framework to guide late-season control decisions.

PMID- 29029236
TI  - First In-Human Experience With Complete Integration of Neuromodulation Device
      Within a Customized Cranial Implant.
AB  - BACKGROUND: Neuromodulation devices have the potential to transform modern day
      treatments for patients with medicine-resistant neurological disease. For
      instance, the NeuroPace System (NeuroPace Inc, Mountain View, California) is a
      Food and Drug Administration (FDA)-approved device developed for closed-loop
      direct brain neurostimulation in the setting of drug-resistant focal epilepsy.
      However, current methods require placement either above or below the skull in
      nonanatomic locations. This type of positioning has several drawbacks including
      visible deformities and scalp pressure from underneath leading to eventual wound
      healing difficulties, micromotion of hardware with infection, and extrusion
      leading to premature explantation. OBJECTIVE: To introduce complete integration
      of a neuromodulation device within a customized cranial implant for
      biocompatibility optimization and prevention of visible deformity. METHODS: We
      report a patient with drug-resistant focal epilepsy despite previous seizure
      surgery and maximized medical therapy. Preoperative imaging demonstrated severe
      resorption of previous bone flap causing deformity and risk for injury. She
      underwent successful responsive neurostimulation device implantation via complete
      integration within a clear customized cranial implant. RESULTS: The patient has
      recovered well without complication and has been followed closely for 180 d.
      Device interrogation with electrocorticographic data transmission has been
      successfully performed through the clear implant material for the first time with
      no evidence of any wireless transmission interference. CONCLUSION: Cranial
      contour irregularities, implant site infection, and bone flap
      resorption/osteomyelitis are adverse events associated with implantable
      neurotechnology. This method represents a novel strategy to incorporate all
      future neuromodulation devices within the confines of a low-profile, computer
      designed cranial implant and the newfound potential to eliminate contour
      irregularities, improve outcomes, and optimize patient satisfaction.

PMID- 29029238
TI  - Toward Understanding the Outcomes of Monkeypox Infection in Human Pregnancy.

PMID- 29029237
TI  - CPAP Does Not Reduce Inflammatory Biomarkers in Patients With Coronary Artery
      Disease and Nonsleepy Obstructive Sleep Apnea: A Randomized Controlled Trial.
AB  - Objectives: Obstructive sleep apnea (OSA) and enhanced vascular inflammation
      coexist in patients with coronary artery disease (CAD). Continuous positive
      airway pressure (CPAP) is first-line treatment for OSA with daytime sleepiness.
      This analysis of data from the RICCADSA (Randomized Intervention with CPAP in
      Coronary Artery Disease and Sleep Apnea) trial investigated the effects of CPAP
      on inflammatory markers in patients with CAD and nonsleepy OSA. Methods: This
      single-center, randomized, controlled, open-label trial enrolled consecutive
      revascularized patients with nonsleepy OSA (apnea-hypopnea index >15/h; Epworth
      Sleepiness Scale score <10). Levels of high-sensitivity C-reactive protein (hs
      CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) were
      measured in blood samples taken at baseline (median 94 days after
      revascularization) and after 1 year of follow-up in patients randomized to CPAP
      or no-CPAP. Results: A total of 220 patients with analyzable blood samples at
      baseline and 1 year were included. Baseline IL-6 levels were significantly lower
      in the CPAP versus no-CPAP group (median 3.1 pmol/L [interquartile range 1.3-5.7]
      vs. 4.2 pmol/L [2.0-8.9], respectively; p = .005). At 1-year follow-up, median IL
      6 levels were significantly reduced in both groups (to 2.2 pmol/L [1.2-3.9] in
      the CPAP group and to 2.2 [1.2-4.7] in no-CPAP group; both p < .001 vs.
      baseline). IL-8, hs-CRP, and TNF-alpha did not change significantly from
      baseline. There was no association between CPAP adherence and changes in
      inflammatory marker levels. Conclusions: In patients with stable CAD and
      nonsleepy OSA, inflammatory biomarkers did not change significantly over time
      except for IL-6 levels, which reduced to the same extent in the CPAP and no-CPAP
      groups. Clinical Trial Registration: ClinicalTrials.gov, ID: NCT00519597;
      researchweb.org, VGSKAS-4731.

PMID- 29029239
TI  - What Does the Sleeping Brain Say? Syntax and Semantics of Sleep Talking in
      Healthy Subjects and in Parasomnia Patients.
AB  - Objectives: Speech is a complex function in humans, but the linguistic
      characteristics of sleep talking are unknown. We analyzed sleep-associated speech
      in adults, mostly (92%) during parasomnias. Methods: The utterances recorded
      during night-time video-polysomnography were analyzed for number of words,
      propositions and speech episodes, frequency, gaps and pauses (denoting turn
      taking in the conversation), lemmatization, verbosity,
      negative/imperative/interrogative tone, first/second person, politeness, and
      abuse. Results: Two hundred thirty-two subjects (aged 49.5 +/- 20 years old; 41%
      women; 129 with rapid eye movement [REM] sleep behavior disorder and 87 with
      sleepwalking/sleep terrors, 15 healthy subjects, and 1 patient with sleep apnea
      speaking in non-REM sleep) uttered 883 speech episodes, containing 59% nonverbal
      utterance (mumbles, shouts, whispers, and laughs) and 3349 understandable words.
      The most frequent word was "No": negations represented 21.4% of clauses (more in
      non-REM sleep). Interrogations were found in 26% of speech episodes (more in non
      REM sleep), and subordinate clauses were found in 12.9% of speech episodes. As
      many as 9.7% of clauses contained profanities (more in non-REM sleep). Verbal
      abuse lasted longer in REM sleep and was mostly directed toward insulting or
      condemning someone, whereas swearing predominated in non-REM sleep. Men sleep
      talked more than women and used a higher proportion of profanities. Apparent turn
      taking in the conversation respected the usual language gaps. Conclusions: Sleep
      talking parallels awake talking for syntax, semantics, and turn-taking in
      conversation, suggesting that the sleeping brain can function at a high level.
      Language during sleep is mostly a familiar, tensed conversation with inaudible
      others, suggestive of conflicts.

PMID- 29029240
TI  - A Greater Extent of Insomnia Symptoms and Physician-Recommended Sleep Medication
      Use Predict Fall Risk in Community-Dwelling Older Adults.
AB  - Study Objectives: Cross-sectional studies suggest that insomnia symptoms are
      associated with falls in later life. This longitudinal study examines the
      independent and interactive effects of the extent of insomnia symptoms (i.e.,
      multiple co-existing insomnia symptoms) and sleep medications on fall risk over a
      2-year follow-up among community-dwelling older adults. Methods: Using data from
      the Health and Retirement Study (2006-2014, N = 6882, Mage = 74.5 years +/- 6.6
      years), we calculated the extent of insomnia symptoms (range = 0-4) participants
      reported (i.e., trouble falling asleep, waking up during the night, waking up too
      early, and not feeling rested). At each wave, participants reported recent sleep
      medications use and falls since the last wave, and were evaluated for balance and
      walking speed. Results: A greater burden of insomnia symptoms and using physician
      recommended sleep medications at baseline independently predicted falling after
      adjusting for known risk factors of falling. The effects of insomnia symptoms on
      fall risk differed by sleep medications use. The extent of insomnia symptoms
      exhibited a positive, dose-response relation with risk of falling among those not
      using sleep medications. Older adults using physician-recommended sleep
      medications exhibited a consistently higher fall risk irrespective of the extent
      of insomnia symptoms. Conclusions: The number of insomnia symptoms predicts 2
      year fall risk in older adults. Taking physician-recommended sleep medications
      increases the risks for falling in older adults, irrespective of the presence of
      insomnia symptoms. Future efforts should be directed toward treating insomnia
      symptoms, and managing and selecting sleep medications effectively to decrease
      the risk of falling in older adults.

PMID- 29029241
TI  - Fragmentary Gene Sequences Negatively Impact Gene Tree and Species Tree
      Reconstruction.
AB  - Species tree reconstruction from genome-wide data is increasingly being
      attempted, in most cases using a two-step approach of first estimating individual
      gene trees and then summarizing them to obtain a species tree. The accuracy of
      this approach, which promises to account for gene tree discordance, depends on
      the quality of the inferred gene trees. At the same time, phylogenomic and
      phylotranscriptomic analyses typically use involved bioinformatics pipelines for
      data preparation. Errors and shortcomings resulting from these preprocessing
      steps may impact the species tree analyses at the other end of the pipeline. In
      this article, we first show that the presence of fragmentary data for some
      species in a gene alignment, as often seen on real data, can result in
      substantial deterioration of gene trees, and as a result, the species tree. We
      then investigate a simple filtering strategy where individual fragmentary
      sequences are removed from individual genes but the rest of the gene is retained.
      Both in simulations and by reanalyzing a large insect phylotranscriptomic data
      set, we show the effectiveness of this simple filtering strategy.

PMID- 29029243
TI  - Considerations in the Use of MDS Research Criteria for Prodromal Parkinson's in
      Rapid Eye Movement Sleep Behaviour Disorder and Population Cohorts.

PMID- 29029242
TI  - Germ Cell Neoplasia in Situ and Preserved Fertility Despite Suppressed
      Gonadotropins in a Patient With Testotoxicosis.
AB  - Context: Testotoxicosis is an autosomal-dominant, male-limited disorder.
      Activating mutations in the luteinizing hormone receptor gene (LHCGR) cause high
      autonomous testosterone secretion, resulting in early-onset peripheral precocious
      puberty. Little is known about long-term consequences of testotoxicosis. Case
      Description: We present a rare case of a patient followed for 25 years with two
      remarkable outcomes: preserved fertility and germ cell neoplasia in situ (GCNIS).
      He presented with precocious puberty at 10 months of age and was diagnosed with
      testotoxicosis due to a de novo heterozygous Asp578Tyr mutation in LHCGR.
      Testicular biopsy in childhood showed Leydig cell hyperplasia with altered cell
      maturation. From infancy throughout adulthood, elevated testosterone and
      estradiol, low inhibin B and anti-Mullerian hormone, and completely suppressed
      follicle-stimulating hormone and luteinizing hormone were noted. Height
      acceleration and advanced bone age resulted in a reduced final height. Semen
      analysis revealed ongoing spermatogenesis, and the patient fathered a child by
      natural conception. Ketoconazole treatment decreased circulating testosterone in
      childhood, supported by experimental suppression of testosterone production in
      his adult testis tissue cultured ex vivo. At 25 years of age, ultrasound revealed
      a testicular tumor, identified as a Leydig cell adenoma, but unexpectedly with
      GCNIS present in adjacent seminiferous tubules. Conclusion: The case illustrates
      that absence of gonadotropins but high intratesticular testosterone concentration
      is sufficient for spermatogenesis and to allow fatherhood. Our study is also the
      first description, to our knowledge, of GCNIS in a patient with testotoxicosis.
      We recommend regular clinical examination and ultrasonic evaluation of the testes
      in these patients due to potential increased risk of malignancy.

PMID- 29029244
TI  - ELMO1 Regulates Autophagy Induction and Bacterial Clearance During Enteric
      Infection.
AB  - Macrophages are specialized phagocytic cells involved in clearing invading
      pathogens. Previously we reported that engulfment and cell motility protein 1
      (ELMO1) in macrophages mediates bacterial internalization and intestinal
      inflammation. Here we studied the role of ELMO1 in the fate of internalized
      targets. ELMO1 is present in the intracellular vesicles and enhances accumulation
      of the protein LC3B following engulfment of Salmonella or treatment with
      autophagy-inducing rapamycin. The protein ATG5 and the kinase ULK1 are involved
      in classical autophagy, while LC3-associated phagocytosis is ULK1 independent.
      ATG5 but not ULK1 cooperated with ELMO1 in LC3 accumulation after infection,
      suggesting the ELMO1 preferentially regulated LC3-associated phagocytosis.
      Because LC3-associated phagocytosis delivers cargo for degradation, the
      contribution of ELMO1 to the lysosome degradation pathways was evaluated by
      studying pH and cathepsin B activity. ELMO1-depleted macrophages showed a time
      dependent increase in pH and a decrease in cathepsin B activity associated with
      bacterial survival. Together, ELMO1 regulates LC3B accumulation and antimicrobial
      responses involved in the clearance of enteric pathogens. This paper investigated
      how innate immune pathways involving ELMO1 work in a coordinated fashion to
      eliminate bacterial threats. ELMO1 is present in the phagosome and enhances
      bacterial clearance by differential regulation of lysosomal acidification and
      enzymatic activity.

PMID- 29029246
TI  - The epidermal growth factor network: role in oocyte growth, maturation and
      developmental competence.
AB  - BACKGROUND: The LH surge induces great physiological changes within the
      preovulatory follicle, which culminate in the ovulation of a mature oocyte that
      is capable of supporting embryo and foetal development. However, unlike mural
      granulosa cells, the oocyte and its surrounding cumulus cells are not directly
      responsive to LH, indicating that the LH signal is mediated by secondary factors
      produced by the granulosa cells. The mechanisms by which the oocyte senses the
      ovulatory LH signal and hence prepares for ovulation has been a subject of
      considerable controversy for the past four decades. Within the last 15 years
      several significant insights have been made into the molecular mechanisms
      orchestrating oocyte development, maturation and ovulation. These findings centre
      on the epidermal growth factor (EGF) pathway and the role it plays in the complex
      signalling network that finely regulates oocyte maturation and ovulation.
      OBJECTIVE AND RATIONALE: This review outlines the role of the EGF network during
      oocyte development and regulation of the ovulatory cascade, and in particular
      focuses on the effect of the EGF network on oocyte developmental competence.
      Application of this new knowledge to advances in ART is examined. SEARCH METHODS:
      The PubMed database was used to search for peer-reviewed original and review
      articles concerning the EGF network. Publications offering a comprehensive
      description of the role of the EGF network in follicle and oocyte development
      were used. OUTCOMES: It is now clear that acute upregulation of the EGF network
      is an essential component of the ovulatory cascade as it transmits the LH signal
      from the periphery of the follicle to the cumulus-oocyte complex (COC). More
      recent findings have elucidated new roles for the EGF network in the regulation
      of oocyte development. EGF signalling downregulates the somatic signal 3'5'
      cyclic guanine monophosphate that suppresses oocyte meiotic maturation and
      simultaneously provides meiotic inducing signals. The EGF network also controls
      translation of maternal transcripts in the quiescent oocyte, a process that is
      integral to oocyte competence. As a means of restricting the ovulatory signal to
      the Graffian follicle, most COCs in the ovary are unresponsive to EGF-ligands.
      Recent studies have revealed that development of a functional EGF signalling
      network in cumulus cells requires dual endocrine (FSH) and oocyte paracrine cues
      (growth differentiation factor 9 and bone morphogenetic protein 15), and this
      occurs progressively in COCs during the last stages of folliculogenesis. Hence, a
      new concept to emerge is that cumulus cell acquisition of EGF receptor
      responsiveness represents a developmental hallmark in folliculogenesis, analogous
      to FSH-induction of LH receptor signalling in mural granulosa cells. Likewise,
      this event represents a major milestone in the oocyte's developmental progression
      and acquisition of developmental competence. It is now clear that EGF signalling
      is perturbed in COCs matured in vitro. This has inspired novel concepts in IVM
      systems to ameliorate this perturbation, resulting in improved oocyte
      developmental competence. WIDER IMPLICATIONS: An oocyte of high quality is
      imperative for fertility. Elucidating the fundamental molecular and cellular
      mechanims by which the EGF network regulates oocyte maturation and ovulation can
      be expected to open new opportunities in ART. This knowledge has already led to
      advances in oocyte IVM in animal models. Translation of such advances into a
      clinical setting should increase the efficacy of IVM, making it a viable
      treatment option for a wide range of patients, thereby simplifying fertility
      treatment and bringing substantial cost and health benefits.

PMID- 29029245
TI  - Host Transcription Profile in Nasal Epithelium and Whole Blood of Hospitalized
      Children Under 2 Years of Age With Respiratory Syncytial Virus Infection.
AB  - Background: Most insights into the cascade of immune events after acute
      respiratory syncytial virus (RSV) infection have been obtained from animal
      experiments or in vitro models. Methods: In this study, we investigated host gene
      expression profiles in nasopharyngeal (NP) swabs and whole blood samples during
      natural RSV and rhinovirus (hRV) infection (acute versus early recovery phase) in
      83 hospitalized patients <2 years old with lower respiratory tract infections.
      Results: Respiratory syncytial virus infection induced strong and persistent
      innate immune responses including interferon signaling and pathways related to
      chemokine/cytokine signaling in both compartments. Interferon-alpha/beta, NOTCH1
      signaling pathways and potential biomarkers HIST1H4E, IL7R, ISG15 in NP samples,
      or BCL6, HIST2H2AC, CCNA1 in blood are leading pathways and hub genes that were
      associated with both RSV load and severity. The observed RSV-induced gene
      expression patterns did not differ significantly in NP swab and blood specimens.
      In contrast, hRV infection did not as strongly induce expression of innate
      immunity pathways, and significant differences were observed between NP swab and
      blood specimens. Conclusions: We conclude that RSV induced strong and persistent
      innate immune responses and that RSV severity may be related to development of T
      follicular helper cells and antiviral inflammatory sequelae derived from high
      activation of BCL6.

PMID- 29029247
TI  - Plasmodium falciparum Infection Early in Pregnancy has Profound Consequences for
      Fetal Growth.
AB  - Malaria during pregnancy constitutes a large health problem in areas of
      endemicity. The World Health Organization recommends that interventions are
      initiated at the first antenatal visit, and these improve pregnancy outcomes.
      This study evaluated fetal growth by ultrasonography and birth outcomes in women
      who were infected prior to the first antenatal visit (gestational age, <120 days)
      and not later in pregnancy. Compared with uninfected controls, women with early
      Plasmodium falciparum exposure had retarded intrauterine growth between
      gestational ages of 212 and 253 days (difference between means, 107 g [95%
      confidence interval {CI}, 26-188]; P = .0099) and a shorter pregnancy duration
      (difference between means, 6.6 days [95% CI, 1.0-112.5]; P = .0087). The birth
      weight (difference between means, 221 g [95% CI, 6-436]; P = .044) and the
      placental weight (difference between means, 84 g [95% CI, 18-150]; P = .013) at
      term were also reduced. The study suggests that early exposure to P. falciparum,
      which is not targeted for prevention by current control strategies, has a
      profound impact on fetal growth, pregnancy duration, and placental weight at
      term.

PMID- 29029249
TI  - Prognostic Factors in Patients With Spinal Chordoma: An Integrative Analysis of
      682 Patients.

PMID- 29029248
TI  - Efficacy of Nanoencapsulated Thymus eriocalyx and Thymus kotschyanus Essential
      Oils by a Mesoporous Material MCM-41 Against Tetranychus urticae (Acari:
      Tetranychidae).
AB  - Inspite of well-established potentiality of plant essential oils as
      biopesticides, their environmentally low persistence is considered as a hindering
      obstacle for its commercialization. In the present study, chemical composition
      and toxicity of essential oils isolated from leaves of Thymus eriocalyx and
      Thymus kotschyanus were evaluated against two-spotted spider mite, Tetranychus
      urticae. The chemicals present in the crude oil were found to be thymol (28.83%),
      oleic acid (11.51%), palmitic acid (8.60%), borneol (5.72%), rho-cymene (3.60%),
      and 1,8-cineole (3.57%) in the essential oil of T. eriocalyx, and camphene
      (35.59%), linalyl acetate (20.47%), linalool (14.75%), alpha-terpineol (13.87%),
      and geranyl acetate (3.07%) in the essential oil of T. kotschyanus. The essential
      oils had strong fumigant toxicity on the adult females of Te. urticae and their
      fumigation persistence was prolonged until 6 and 5 d, respectively, for T.
      eriocalyx and T. kotschyanus. Loading of essential oils in MCM-41 increased their
      stability and persistence was extended up to 20 and 18 d for T. eriocalyx and T.
      kotschyanus. Further, mite mortality increased from 80 to 203 mites by T.
      eriocalyx and from 58 to 186 mites by T. kotschyanus nanoencapsulated essential
      oils. Based on these results, nanoencapsulation of T. eriocalyx and T.
      kotschyanus essential oils in MCM-41 may be a useful method for their application
      in the management of Te. urticae.

PMID- 29029251
TI  - Effects of the Botanical Compound p-Anisaldehyde on Horn Fly (Diptera: Muscidae)
      Repellency, Mortality, and Reproduction.
AB  - The horn fly, Haematobia irritans irritans (L.) (Diptera: Muscidae), is an
      economically important obligate blood feeder that mainly attacks cattle in
      Europe, Asia, and North and South America. As horn fly resistance to conventional
      insecticides becomes more common, alternative control tactics, such as
      application of bioactive botanical natural products are being investigated. p
      Anisaldehyde has been found in many plant species, and it has shown effects that
      include mortality, attractancy, and interference with host seeking. The series of
      bioassays we developed was effective for assessing a range of horn fly responses
      to chemicals and probably those of some other filth fly species. In our study, p
      anisaldehyde was lethal to horn fly eggs at concentrations of 0.00001%, and
      possibly less. Mixed into cow manure, 5000-20,000 ppm p-anisaldehyde reduced horn
      fly larvae by 85.4%-100%. p-Anisaldehyde caused some immobilization of adult horn
      flies when exposed by direct contract with spray droplets and by fumigation.
      Mortality was 90%-100% in response to 5%-10% concentrations by 30 min, and LD50
      and LD90 values are reported for five times from 30 min-4 h. Complete horn fly
      mortality was achieved by fumigation with 0.75% p-anisaldehyde by 3 h in an
      enclosed space, and we determined that fumigation was more (~12.5-fold) lethal to
      adult horn flies than sprayed droplets. Although horn flies were not repelled by
      p-anisaldehyde in static air tube olfactometers, the compound completely deterred
      feeding from cotton pads soaked in bovine blood in response to concentrations of
      0.6% and greater in ventilated containers. Although horn fly control is not
      likely to use fumigation methods, p-anisaldehyde might be useful for adult
      control using sprays and egg and larval control using feed-through techniques.
      Exposure to sublethal concentrations of p-anisaldehyde did not affect horn fly
      egg production and hatching. Aside from causing different responses in the same
      species of arthropod, p-anisaldehyde has a variety of effects on other
      arthropods. Research on this compound as a potentially multifaceted pest
      management tool has been sparse. This study, for example, is the first to
      demonstrate p-anisaldehyde's feeding deterrent and immobilization properties and
      effects on different life stages.

PMID- 29029250
TI  - Actigraphy-Derived Daily Rest-Activity Patterns and Body Mass Index in Community
      Dwelling Adults.
AB  - Study Objectives: To examine associations between 24-hour rest-activity patterns
      and body mass index (BMI) among community-dwelling US adults. Rest-activity
      patterns provide a field method to study exposures related to circadian rhythms.
      Methods: Adults (N = 578) wore an actigraph on their nondominant wrist for 7
      days. Intradaily variability and interdaily stability (IS), M10 (most active 10
      hours), L5 (least active 5-hours), and relative amplitude (RA) were derived using
      nonparametric rhythm analysis. Mesor, acrophase, and amplitude were calculated
      from log-transformed count data using the parametric cosinor approach. Results:
      Participants were 80% female and mean (standard deviation) age was 52 (15) years.
      Participants with higher BMI had lower values for magnitude, RA, IS, total sleep
      time (TST), and sleep efficiency. In multivariable analyses, less robust 24-hour
      rest-activity patterns as represented by lower RA were consistently associated
      with higher BMI: comparing the bottom quintile (least robust) to the top quintile
      (most robust 24-hour rest-activity pattern) of RA, BMI was 3-kg/m2 higher (p =
      .02). Associations were similar in magnitude to an hour less of TST (1-kg/m2
      higher BMI) or a 10% decrease in sleep efficiency (2-kg/m2 higher BMI), and
      independent of age, sex, race, education, and the duration of rest and/or
      activity. Conclusions: Lower RA, reflecting both higher night activity and lower
      daytime activity, was associated with higher BMI. Independent of the duration of
      rest or activity during the day or night, 24-hour rest, and activity patterns
      from actigraphy provide aggregated measures of activity that associate with BMI
      in community-dwelling adults.

PMID- 29029252
TI  - Time-on-Task Effect During Sleep Deprivation in Healthy Young Adults Is Modulated
      by Dopamine Transporter Genotype.
AB  - Study Objectives: The time-on-task (TOT) effect and total sleep deprivation (TSD)
      have similar effects on neurobehavioral functioning, including increased
      performance instability during tasks requiring sustained attention. The TOT
      effect is exacerbated by TSD, suggesting potentially overlapping mechanisms. We
      probed these mechanisms by investigating genotype-phenotype relationships on
      psychomotor vigilance test (PVT) performance for 3 a-priori selected genes
      previously linked to the TOT effect and/or TSD: dopamine active transporter 1
      (DAT1), catechol-O-methyltransferase (COMT), and tumor necrosis factor alpha
      (TNFalpha). Methods: N = 82 healthy adults participated in 1 of 3 laboratory
      studies. A 10-min PVT was administered repeatedly during 38 h of TSD. We assessed
      changes in response time (RT) across each minute of the PVT as a function of time
      awake and genotype. Additionally, cumulative relative RT frequency distributions
      were constructed to examine changes in performance from the first to the second 5
      min of the PVT as a function of genotype. Results: DAT1, COMT, and TNFalpha were
      associated with differences in the build-up of the TOT effect across the 10-min
      PVT. DAT1 additionally modulated the interaction between TSD and the TOT effect.
      Subjects homozygous for the DAT1 10-repeat allele were relatively protected
      against TOT deficits on the PVT during TSD compared to carriers of the 9-repeat
      allele. Conclusions: DAT1 is known to regulate dopamine reuptake and is highly
      expressed in the striatum. Our results implicate striatal dopamine in mechanisms
      involved in performance instability that appear to be common to TSD and the TOT
      effect. Furthermore, DAT1 may be a candidate biomarker of resilience to the build
      up of performance impairment across TOT due to TSD.

PMID- 29029254
TI  - Retrospective Proteomic Analysis of Serum After Akhmeta Virus Infection: New
      Suspect Case Identification and Insights Into Poxvirus Humoral Immunity.
AB  - Serologic cross-reactivity, a hallmark of orthopoxvirus (OPXV) infection, makes
      species-specific diagnosis of infection difficult. In this study, we used a
      variola virus proteome microarray to characterize and differentiate antibody
      responses to nonvaccinia OPXV infections from smallpox vaccination. The profile
      of 2 case patients infected with newly discovered OPXV, Akhmeta virus, exhibited
      antibody responses of greater intensity and broader recognition of viral proteins
      and includes the B21/22 family glycoproteins not encoded by vaccinia virus
      strains used as vaccines. An additional case of Akhmeta virus, or nonvaccinia
      OPXV infection, was identified through community surveillance of individuals with
      no or uncertain history of vaccination and no recent infection. The results
      demonstrate the utility of microarrays for high-resolution mapping of antibody
      response to determine the nature of OPXV exposure.

PMID- 29029253
TI  - Breathing Disturbances Without Hypoxia Are Associated With Objective Sleepiness
      in Sleep Apnea.
AB  - Study Objectives: To determine whether defining two subtypes of sleep-disordered
      breathing (SDB) events-with or without hypoxia-results in measures that are more
      strongly associated with hypertension and sleepiness. Methods: A total of 1022
      participants with 2112 nocturnal polysomnograms from the Wisconsin Sleep Cohort
      were analyzed with our automated algorithm, developed to detect breathing
      disturbances and desaturations. Breathing events were time-locked to
      desaturations, resulting in two indices-desaturating (hypoxia-breathing
      disturbance index [H-BDI]) and nondesaturating (nonhypoxia-breathing disturbance
      index [NH-BDI]) events-regardless of arousals. Measures of subjective (Epworth
      Sleepiness Scale) and objective (2981 multiple sleep latency tests from a subset
      of 865 participants) sleepiness were analyzed, in addition to clinically relevant
      clinicodemographic variables. Hypertension was defined as BP >= 140/90 or
      antihypertensive use. Results: H-BDI, but not NH-BDI, correlated strongly with
      SDB severity indices that included hypoxia (r >= 0.89, p <= .001 with 3% oxygen
      desaturation index [ODI] and apnea hypopnea index with 4% desaturations). A
      doubling of desaturation-associated events was associated with hypertension
      prevalence, which was significant for ODI but not H-BDI (3% ODI OR = 1.06, 95% CI
      = 1.00-1.12, p < .05; H-BDI OR 1.04, 95% CI = 0.98-1.10) and daytime sleepiness
      (beta = 0.20 Epworth Sleepiness Scale [ESS] score, p < .0001; beta = -0.20
      minutes in MSL on multiple sleep latency test [MSLT], p < .01). Independently,
      nondesaturating event doubling was associated with more objective sleepiness
      (beta = -0.52 minutes in MSL on MSLT, p < .001), but had less association with
      subjective sleepiness (beta = 0.12 ESS score, p = .10). In longitudinal analyses,
      baseline nondesaturating events were associated with worsening of H-BDI over a 4
      year follow-up, suggesting evolution in severity. Conclusions: In SDB,
      nondesaturating events are independently associated with objective daytime
      sleepiness, beyond the effect of desaturating events.

PMID- 29029255
TI  - Plasmids can transfer to Clostridium difficile CD37 and 630Deltaerm both by a
      DNase resistant conjugation-like mechanism and a DNase sensitive mechanism.
AB  - Broad host range conjugative plasmids that replicate in Escherichia coli have
      been widely used to mobilise smaller replicons, bearing their cognate origin of
      transfer (oriT) into a variety of organisms that are less tractable genetically,
      such as Clostridium (Clostridioides) difficile. In this work we demonstrated that
      the oriT region of pMTL9301 (derived from RK2) is not required for transfer
      between E. coli and C. difficile strains 630Deltaerm and CD37 and that this oriT
      independent transfer is abolished in the presence of DNase when CD37 is the
      recipient. Transfer to the 630Deltaerm strain is DNase resistant even without an
      obvious oriT, when E. coli CA434 is used as a donor and is sensitive to DNase
      when E. coli HB101 is the donor.

PMID- 29029256
TI  - Multicentre validation of 4-well azole agar plates as a screening method for
      detection of clinically relevant azole-resistant Aspergillus fumigatus.
AB  - Objectives: Azole-resistant Aspergillus fumigatus is emerging worldwide.
      Reference susceptibility testing methods are technically demanding and no
      validated commercial susceptibility tests for moulds currently exist. In this
      multicentre study a 4-well azole-containing screening agar method was evaluated
      using clinically relevant isolates. Methods: Forty WT and 39 cyp51A mutant A.
      fumigatus [G54 (n = 10), M220 (n = 10), TR34/L98H (n = 9) and TR46/Y121F/T289A (n
      = 10)] were tested individually and as simulated mixed samples (sampling 4 WT and
      1 mutant colonies). EUCAST MICs were determined following E.Def 9.3. In-house and
      commercial 4-well plates containing agars supplemented with 4 mg/L itraconazole,
      1 mg/L voriconazole, 0.5 mg/L posaconazole and no antifungal, respectively, were
      evaluated. Growth was scored (0-3) by two independent observers in three
      laboratories. Inter-plate, inter-observer, essential and categorical agreement,
      sensitivity and specificity were calculated. Results: CYP51A genotype and
      antifungal compound-specific MICs and growth patterns were documented. The inter
      observer agreement was excellent with 86%-99% identical scores (range 80%-100%)
      for both plates. The qualitative agreement (no growth versus growth) was
      excellent (median 95%-100%, range 87%-100%, overall). The overall sensitivity and
      specificity for the 4-well plate (no growth versus growth) was 99% (range 97%
      100%) and 99% (95%-100%), respectively. The sensitivity for simulated WT/mutant
      specimens was 94% (range 83%-100%) for the WT-TR34/L98H combination, but 100% for
      the WT/G54W combination. The performance remained unchanged using only
      itraconazole- and voriconazole-containing agars, but was lower for the other
      combinations. Conclusions: Implementation of the 4-well screening plate in
      routine laboratories will allow easy and reliable detection of the most common
      azole-resistant A. fumigatus.

PMID- 29029258
TI  - Acupuncture Improves Peri-menopausal Insomnia: A Randomized Controlled Trial.
AB  - Study Objectives: To evaluate the short-term efficacy of acupuncture for the
      treatment of peri-menopausal insomnia (PMI). Methods: Design: A randomized,
      participant-blind, placebo-controlled trial consisted of the acupuncture group (n
      = 38) and placebo-acupuncture group (n = 38). Setting: A tertiary teaching and
      general hospital. Participants: 76 peri-menopausal women with insomnia disorder
      based on the International Classification of Sleep Disorders, Third Edition.
      Interventions: A 10-session of acupuncture at bilateral Shenshu (BL 23) and
      Ganshu (BL 18) with unilateral Qimen (LR 14) and Jingmen (GB 25) or Streitberger
      needles at the same acupoints was performed for over 3 weeks. Measurements:
      Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) with over
      night polysomnography (PSG) exam were completed at baseline and post-treatment.
      Results: After the treatments, the decrease from baseline in PSQI score was 8.03
      points in acupuncture group and 1.29 points in placebo-acupuncture group. The
      change from baseline in ISI score was 11.35 points in acupuncture group and 2.87
      points in placebo-acupuncture group. In PSG data, acupuncture significantly
      improved the sleep efficiency and total sleep time, associated with less wake
      after sleep onset and lower percent stage 1 after the treatment. No significant
      differences from baseline to post-treatment were found in placebo-acupuncture
      group. Conclusions: Acupuncture can contribute to a clinically relevant
      improvement in the short-term treatment of PMI, both subjectively and
      objectively. Clinical Trial Registration: Acupuncture for peri-menopause
      insomnia: a randomized controlled trial,
      http://www.chictr.org.cn/showproj.aspx?proj=12118 ChiCTR-IPR-15007199, China.

PMID- 29029259
TI  - First Experimental Assessment of Protein Intrinsic Disorder Involvement in an RNA
      Virus Natural Adaptive Process.
AB  - Intrinsic disorder (ID) in proteins is defined as a lack of stable structure in
      physiological conditions. Intrinsically disordered regions (IDRs) are highly
      abundant in some RNA virus proteomes. Low topological constraints exerted on IDRs
      are expected to buffer the effect of numerous deleterious mutations and could be
      related to the remarkable adaptive potential of RNA viruses to overcome
      resistance of their host. To experimentally test this hypothesis in a natural
      pathosystem, a set of four variants of Potato virus Y (PVY; Potyvirus genus)
      containing various ID degrees in the Viral genome-linked (VPg) protein, a key
      determinant of potyvirus adaptation, was designed. To estimate the ID
      contribution to the VPg-based PVY adaptation, the adaptive ability of the four
      PVY variants was monitored in the pepper host (Capsicum annuum) carrying a
      recessive resistance gene. Intriguingly, the two mutants with the highest ID
      content displayed a significantly higher ability to restore infection in the
      resistant host, whereas the less intrinsically disordered mutant was unable to
      restore infection. The role of ID on virus adaptation may be due either to a
      larger exploration of evolutionary pathways or the minimization of fitness
      penalty caused by resistance-breaking mutations. This pioneering study strongly
      suggests the positive impact of ID in an RNA virus adaptive capacity.

PMID- 29029261
TI  - From the Cover: Selective Enhancement of Domoic Acid Toxicity in Primary Cultures
      of Cerebellar Granule Cells by Lowering Extracellular Na+ Concentration.
AB  - Domoic acid (DOM) is an excitatory amino acid analog of kainic acid (KA) that
      acts through glutamic acid (GLU) receptors, inducing a fast and potent neurotoxic
      response. Here, we present evidence for an enhancement of excitotoxicity
      following exposure of cultured cerebellar granule cells to DOM in the presence of
      lower than physiological Na+ concentrations. The concentration of DOM that
      reduced by 50% neuronal survival was approximately 3 uM in Na+-free conditions
      and 16 uM in presence of a physiological concentration of extracellular Na+. The
      enhanced neurotoxic effect of DOM was fully prevented by AMPA/KA receptor
      antagonist, while N-methyl-D-aspartate-receptor-mediated neurotoxicity did not
      seem to be involved, as the absence of extracellular Na+ failed to potentiate GLU
      excitotoxicity under the same experimental conditions. Lowering of extracellular
      Na+ concentration to 60 mM eliminated extracellular recording of spontaneous
      electrophysiological activity from cultured neurons grown on a multi electrode
      array and prevented DOM stimulation of the electrical activity. Although changes
      in the extracellular Na+ concentration did not alter the magnitude of the rapid
      increase in intracellular Ca2+ levels associated to DOM exposure, they did change
      significantly the contribution of voltage-sensitive calcium channels (VScaCs) and
      the recovery time to baseline. The prevention of Ca2+ influx via VSCaCs by
      nifedipine failed to prevent DOM toxicity at any extracellular Na+ concentration,
      while the reduction of extracellular Ca2+ concentration ameliorated DOM toxicity
      only in the absence of extracellular Na+, enhancing it in physiological
      conditions. Our data suggest a crucial role for extracellular Na+ concentration
      in determining excitotoxicity by DOM.

PMID- 29029260
TI  - An Adjuvanted, Postfusion F Protein-Based Vaccine Did Not Prevent Respiratory
      Syncytial Virus Illness in Older Adults.
AB  - Background: Respiratory syncytial virus (RSV) is an important cause of illness in
      older adults. This study assessed efficacy of a vaccine for prevention of RSV
      associated acute respiratory illness (ARI), defined by specified symptoms with
      virologic confirmation. Methods: This phase 2b study evaluated RSV postfusion F
      protein (120 ug) with glucopyranosyl lipid adjuvant (5 ug) in 2% stable emulsion.
      Subjects aged >=60 years were randomly assigned at a ratio of 1:1 to receive
      vaccine or placebo (all received inactivated influenza vaccine). Ill subjects
      recorded symptoms and provided blood and nasal swab samples. Results: In the per
      protocol population (n = 1894), the incidence of RSV-associated ARI occurring
      >=14 days after dosing was 1.7% and 1.6% in the vaccine and placebo groups,
      respectively, for a vaccine efficacy (VE) of -7.1% (90% confidence interval [CI],
      -106.9%-44.3%). Efficacy was not observed in secondary analyses that included
      seroresponse to nonvaccine RSV antigens (VE, 8.9%; 90% CI, -28.5%-35.4%) or
      symptoms combined with seroresponse (VE, 10.0%; 90% CI, -45.4%-44.4%). On day 29,
      92.9% of vaccinees had an anti-F immunoglobulin G antibody seroresponse. Overall,
      48.5% and 30.9% of RSV vaccine recipients reported local and systemic solicited
      symptoms, respectively. Conclusion: The RSV vaccine was immunogenic but did not
      protect older adults from RSV illness. Clinical Trials Registration: NCT02508194.

PMID- 29029262
TI  - Chikungunya fever outbreak identified in North Bali, Indonesia.
AB  - Background: Chikungunya virus (CHIKV) infections have been reported sporadically
      within the last 5 years in several areas of Indonesia including Bali. Most of the
      reports, however, have lacked laboratory confirmation. Method: A recent fever
      outbreak in a village in the North Bali area was investigated using extensive
      viral diagnostic testing including both molecular and serological approaches.
      Results and conclusions: Ten out of 15 acute febrile illness samples were
      confirmed to have CHIKV infection by real-time PCR or CHIKV-specific IgM enzyme
      linked immunosorbent assay (ELISA). The outbreak strain belonged to the Asian
      genotype with highest homology to other CHIKV strains currently circulating in
      Indonesia. The results are of public health concern particularly because Bali is
      a popular tourist destination in Indonesia and thereby the potential to spread
      the virus to non-endemic areas is high. GenBank accession numbers: KY885022,
      KY885023, KY885024, KY885025, KY885026, KY885027.

PMID- 29029264
TI  - A General Model for Estimating Macroevolutionary Landscapes.
AB  - The evolution of quantitative characters over long timescales is often studied
      using stochastic diffusion models. The current toolbox available to students of
      macroevolution is however limited to two main models: Brownian motion and the
      Ornstein-Uhlenbeck process, plus some of their extensions. Here, we present a
      very general model for inferring the dynamics of quantitative characters evolving
      under both random diffusion and deterministic forces of any possible shape and
      strength, which can accommodate interesting evolutionary scenarios like
      directional trends, disruptive selection, or macroevolutionary landscapes with
      multiple peaks. This model is based on a general partial differential equation
      widely used in statistical mechanics: the Fokker-Planck equation, also known in
      population genetics as the Kolmogorov forward equation. We thus call the model
      FPK, for Fokker-Planck-Kolmogorov. We first explain how this model can be used to
      describe macroevolutionary landscapes over which quantitative traits evolve and,
      more importantly, we detail how it can be fitted to empirical data. Using
      simulations, we show that the model has good behavior both in terms of
      discrimination from alternative models and in terms of parameter inference. We
      provide R code to fit the model to empirical data using either maximum-likelihood
      or Bayesian estimation, and illustrate the use of this code with two empirical
      examples of body mass evolution in mammals. FPK should greatly expand the set of
      macroevolutionary scenarios that can be studied since it opens the way to
      estimating macroevolutionary landscapes of any conceivable shape. [Adaptation;
      bounds; diffusion; FPK model; macroevolution; maximum-likelihood estimation; MCMC
      methods; phylogenetic comparative data; selection.].

PMID- 29029263
TI  - Role of STAT3 in skin fibrosis and transforming growth factor beta signalling.
AB  - Objective: SSc is an autoimmune disease characterized by progressive fibrosis of
      the skin and internal organs. IL-6 and related cytokines that signal through
      STAT3 have been implicated in the pathogenesis of SSc and mouse models of
      fibrosis. The aim of this study was to investigate the efficacy of inhibiting
      STAT3 in the development of fibrosis in two mouse models of skin fibrosis.
      Methods: Biopsy samples of skin from SSc patients and healthy control subjects
      were used to determine the expression pattern of phosphotyrosyl (pY705)-STAT3.
      C188-9, a small molecule inhibitor of STAT3, was used to treat fibrosis in the
      bleomycin-induced fibrosis model and Tsk-1 mice. In vitro studies were performed
      to determine the extent to which STAT3 regulates the fibrotic phenotype of dermal
      fibroblasts. Results: Increased STAT3 and pY705-STAT3 was observed in SSc skin
      biopsies and in both mouse models of SSc. STAT3 inhibition with C188-9 resulted
      in attenuated skin fibrosis, myofibroblast accumulation, pro-fibrotic gene
      expression and collagen deposition in both mouse models of skin fibrosis. C188-9
      decreased in vitro dermal fibroblast production of fibrotic genes induced by IL-6
      trans-signalling and TGF-beta. Finally, TGF-beta induced phosphotyrosylation of
      STAT3 in a SMAD3-dependent manner. Conclusion: STAT3 inhibition decreases dermal
      fibrosis in two models of SSc. STAT3 regulates dermal fibroblasts function in
      vitro and can be activated by TGF-beta. These data suggest that STAT3 is a
      potential therapeutic target for dermal fibrosis in diseases such as SSc.

PMID- 29029266
TI  - Investigation of Human Immunodeficiency Virus Outbreaks Among People Who Inject
      Drugs: Timely Diagnosis and Molecular Surveillance are Crucial.

PMID- 29029257
TI  - Beyond the bulk: disclosing the life of single microbial cells.
AB  - Microbial single cell analysis has led to discoveries that are beyond what can be
      resolved with population-based studies. It provides a pristine view of the
      mechanisms that organize cellular physiology, unbiased by population
      heterogeneity or uncontrollable environmental impacts. A holistic description of
      cellular functions at the single cell level requires analytical concepts beyond
      the miniaturization of existing technologies, defined but uncontrolled by the
      biological system itself. This review provides an overview of the latest advances
      in single cell technologies and demonstrates their potential. Opportunities and
      limitations of single cell microbiology are discussed using selected application
      related examples.

PMID- 29029265
TI  - Preclinical testing of a broad-spectrum antimicrobial endotracheal tube coated
      with an innate immune synthetic mimic.
AB  - Background: Endotracheal tubes provide an abiotic surface on which bacteria and
      fungi form biofilms, and the release of endotoxins and planktonic organisms can
      cause damaging inflammation and infections. Objectives: Ceragenins are small
      molecule mimics of antimicrobial peptides with broad-spectrum antibacterial and
      antifungal activity, and a ceragenin may be used to provide antimicrobial
      protection to the abiotic surface of an endotracheal tube. Methods: A hydrogel
      film, containing CSA-131, was generated on endotracheal tubes. Elution of CSA-131
      was quantified in drip-flow and static systems, antifungal and antibacterial
      activity was measured with repeated inoculation in growth media, biofilm
      formation was observed through electron microscopy, safety was determined by
      intubation of pigs with coated and uncoated endotracheal tubes. Results:
      Optimized coatings containing CSA-131 provided controlled elution of CSA-131,
      with concentrations released of less than 1 MUg/mL. The eluting ceragenin
      prevented fungal and bacterial colonization of coated endotracheal tubes for
      extended periods, while uncoated tubes were colonized by bacteria and fungi.
      Coated tubes were well tolerated in intubated pigs. Conclusions: Thin films
      containing CSA-131 provide protection against microbial colonization of
      endotracheal tubes. This protection prevents fungal and bacterial biofilm
      formation on the tubes and reduces endotoxin associated with tubes. This coating
      is well suited for decreasing the adverse effects of intubation associated with
      infection and inflammation.

PMID- 29029267
TI  - Evaluation of universal versus genotype-guided efavirenz dose reduction in
      pregnant women using population pharmacokinetic modelling.
AB  - Objectives: Lack of data on the pharmacokinetics of efavirenz in pregnant women
      at the 400 mg reduced dose currently prevents universal roll-out. Population
      pharmacokinetic modelling was used to explore pharmacokinetic endpoints at 200,
      400 and 600 mg daily doses in pregnant women stratified by CYP2B6 metabolic
      status. Methods: The analysis was based on 252 plasma efavirenz concentrations
      from 77 pregnant women (77 sparse, 175 intensive) who received antiretroviral
      regimens containing 600 mg of efavirenz. The model was developed using NONMEM(r).
      The effect of genetics was investigated and concentration-time courses at steady
      state were simulated for individuals (n = 1000 each) classified as CYP2B6 slow,
      intermediate and fast metabolizers at 200, 400 and 600 mg daily doses. Results:
      At a 400 mg reduced dose, predicted mean (90% CI) mid-dose efavirenz
      concentration (C12) was 2.24 MUg/mL (0.89-4.18) in pregnant women classified as
      slow metabolizers, compared with 0.87 MUg/mL (0.34-1.64) in intermediate
      metabolizers and 0.78 MUg/mL (0.30-1.47) in fast metabolizers. C12 was below the
      0.47 MUg/mL threshold determined within the ENCORE 1 trial in 10% at 400 mg, 4.6%
      at 600 mg and 3.4% with genotype-guided dosing. The 4.0 MUg/mL toxicity threshold
      was exceeded in 4.6% at 400 mg, 13.5% at 600 mg and 5.2% with genotype-guided
      dosing. Conclusions: These data provide context for the ongoing debate about
      reduction in efavirenz dose to 400 mg during pregnancy and should be interpreted
      alongside the lower toxicity expected with the lower dose. Additional research is
      required to investigate genotype-guided dose reduction in pregnant women.

PMID- 29029268
TI  - Development and Validation of a Method for the Detection of alpha- and beta
      Endosulfan (Organochlorine Insecticide) in Calliphora vomitoria (Diptera:
      Calliphoridae).
AB  - Entomotoxicology studies employ analytical methods and instrumentation to detect
      chemical substances in carrion insects feeding from the decomposing tissues. The
      identification of such chemicals may determine the cause of death and may be used
      for the estimation of the minimum time since death. To date, the main focus of
      entomotoxicological studies has been the detection of drugs, whereas little
      information concerns the effects of pesticides on blowflies. Pesticides are
      generally freely available and more affordable than drugs but they can also be a
      home hazard and an accessible candidate poison at a crime scene. A QuEChERS
      extraction method followed by Gas chromatography-mass spectrometry (GC-MS)
      analysis was developed for the detection of alpha- and beta-endosulfan
      (organochlorine insecticide and acaricide) in Calliphora vomitoria L. (Diptera:
      Calliphoridae) and validated. Furthermore, the effects of endosulfan on the
      morphology, development time and survival of the immature blowflies were
      investigated. Larvae were reared on liver substrates homogeneously spiked with
      aliquots of endosulfan corresponding to the concentrations found in body tissues
      of humans and animals involved in endosulfan poisoning. Results demonstrated that
      the combination of QuEChERS extraction and GC-MS provide an adequate methods to
      detect both alpha- and beta-endosulfan in blowfly immatures. Furthermore, the
      presence of alpha- and beta-endosulfan in the food source 1) prevented C.
      vomitoria immatures reaching the pupal instar and, therefore, the adult instar at
      high concentrations, 2) did not affect the developmental time of blowflies at low
      concentrations 3) affected the size of immatures only at high concentrations,
      resulting in significantly smaller larvae.

PMID- 29029269
TI  - An Overlooked Paleotetraploidization in Cucurbitaceae.
AB  - Cucurbitaceae plants are of considerable biological and economic importance, and
      genomes of cucumber, watermelon, and melon have been sequenced. However, a
      comparative genomics exploration of their genome structures and evolution has not
      been available. Here, we aimed at performing a hierarchical inference of genomic
      homology resulted from recursive paleopolyploidizations. Unexpectedly, we found
      that, shortly after a core-eudicot-common hexaploidy, a cucurbit-common
      tetraploidization (CCT) occurred, overlooked by previous reports. Moreover, we
      characterized gene loss (and retention) after these respective events, which were
      significantly unbalanced between inferred subgenomes, and between plants after
      their split. The inference of a dominant subgenome and a sensitive one suggested
      an allotetraploid nature of the CCT. Besides, we found divergent evolutionary
      rates among cucurbits, and after doing rate correction, we dated the CCT to be 90
      102 Ma, likely common to all Cucurbitaceae plants, showing its important role in
      the establishment of the plant family.

PMID- 29029270
TI  - Does Active Oral Sex Contribute to Female Infertility?
AB  - Based on recent, historical, and circumstantial evidence, we present a
      multifactorial hypothesis that has potential direct implications on the
      epidemiology and management of chlamydial infection and disease in humans. We
      propose that (1) like its veterinary relatives, the oculogenital pathogen
      Chlamydia trachomatis evolved as a commensal organism of the human
      gastrointestinal (GI) tract primarily transmissible via the fecal-oral route; (2)
      in the modern era, C. trachomatis causes "opportunistic" infection at non-GI
      sites under conditions driven by improved sanitation/hygiene and reduced fecal
      oral transmission; and (3) the rise in the practice of oral sex is contributing
      to the increased prevalence of C. trachomatis in the human GI tract. Infectious
      organisms produced in the GI tract and reaching the rectum may then chronically
      contaminate and infect the female urogenital tract, thereby potentially
      contributing to the most serious sequelae of chlamydial infection in women:
      pelvic inflammatory disease, ectopic pregnancy, and tubal factor infertility.

PMID- 29029272
TI  - BSR and BHPR guideline for the prescription and monitoring of non-biologic
      disease-modifying anti-rheumatic drugs.

PMID- 29029273
TI  - The Citizen Science Project 'Mueckenatlas' Helps Monitor the Distribution and
      Spread of Invasive Mosquito Species in Germany.
AB  - The citizen science project 'Mueckenatlas' (mosquito atlas) was implemented in
      early 2012 to improve mosquito surveillance in Germany. Citizens are asked to
      support the spatiotemporal mapping of culicids by submitting mosquito specimens
      collected in their private surroundings. The Mueckenatlas has developed into an
      efficient tool for data collection with close to 30,000 mosquitoes submitted by
      the end of 2015. While the vast majority of submissions included native mosquito
      species, a small percentage represented invasive species. The discovery of Aedes
      albopictus (Skuse) (Diptera: Culicidae), Aedes japonicus japonicus (Theobald)
      (Diptera: Culicidae) and Aedes koreicus (Edwards) (Diptera: Culicidae) specimens
      via the Mueckenatlas project prompted targeted monitoring activities in the field
      which produced additional information on the distribution of these species in
      Germany. Among others, Mueckenatlas submissions led to the detection of three
      populations of Ae. j. japonicus in West, North and Southeast Germany in 2012,
      2013, and 2015, respectively. As demonstrated by on-site monitoring, the origins
      of Ae. j. japonicus specimens submitted to the Mueckenatlas mirror the
      distribution areas of the four presently known German populations as found by
      active field sampling (the fourth population already reported prior to the launch
      of the Mueckenatlas). The data suggest that a citizen science project such as the
      Mueckenatlas may aid in detecting changes in the mosquito fauna and can therefore
      be used to guide the design of more targeted field surveillance activities.

PMID- 29029271
TI  - Sequence and Structural Diversity of Mouse Y Chromosomes.
AB  - Over the 180 My since their origin, the sex chromosomes of mammals have evolved a
      gene repertoire highly specialized for function in the male germline. The mouse Y
      chromosome is unique among mammalian Y chromosomes characterized to date in that
      it is large, gene-rich and euchromatic. Yet, little is known about its diversity
      in natural populations. Here, we take advantage of published whole-genome
      sequencing data to survey the diversity of sequence and copy number of sex-linked
      genes in three subspecies of house mice. Copy number of genes on the repetitive
      long arm of both sex chromosomes is highly variable, but sequence diversity in
      nonrepetitive regions is decreased relative to expectations based on autosomes.
      We use simulations and theory to show that this reduction in sex-linked diversity
      is incompatible with neutral demographic processes alone, but is consistent with
      recent positive selection on genes active during spermatogenesis. Our results
      support the hypothesis that the mouse sex chromosomes are engaged in ongoing
      intragenomic conflict.

PMID- 29029274
TI  - Mutation-Driven Parallel Evolution during Viral Adaptation.
AB  - Convergent evolution has been demonstrated across all levels of biological
      organization, from parallel nucleotide substitutions to convergent evolution of
      complex phenotypes, but whether instances of convergence are the result of
      selection repeatedly finding the same optimal solution to a recurring problem or
      are the product of mutational biases remains unsettled. We generated 20 replicate
      lineages allowed to fix a single mutation from each of four bacteriophage
      genotypes under identical selective regimes to test for parallel changes within
      and across genotypes at the levels of mutational effect distributions and gene,
      protein, amino acid, and nucleotide changes. All four genotypes shared a
      distribution of beneficial mutational effects best approximated by a distribution
      with a finite upper bound. Parallel adaptation was high at the protein, gene,
      amino acid, and nucleotide levels, both within and among phage genotypes, with
      the most common first-step mutation in each background fixing on an average in 7
      of 20 replicates and half of the substitutions in two of the four genotypes
      occurring at shared sites. Remarkably, the mutation of largest beneficial effect
      that fixed for each genotype was never the most common, as would be expected if
      parallelism were driven by selection. In fact, the mutation of smallest benefit
      for each genotype fixed in a total of 7 of 80 lineages, equally as often as the
      mutation of largest benefit, leading us to conclude that adaptation was largely
      mutation-driven, such that mutational biases led to frequent parallel fixation of
      mutations of suboptimal effect.

PMID- 29029275
TI  - Surgical Management of Intrinsic Tumors of the Facial Nerve.
AB  - BACKGROUND: Intrinsic tumors of the facial nerve are a rare entity. Dealing with
      this subset of tumors is challenging both in terms of decision making and
      surgical intervention. OBJECTIVE: To review the outcomes of surgical management
      of facial nerve tumors and cable nerve graft interpositioning. METHODS: A
      retrospective analysis was performed at a referral center for skull base
      pathology. One hundred fifteen patients who were surgically treated for facial
      nerve tumors were included. In case of nerve interruption during surgery, the
      cable nerve interpositioning technique was employed wherein the facial nerve
      palsy lasted for less than 1-yr duration. In cases of facial nerve palsy lasting
      for greater than 1 yr, the nerve was restituted by a hypoglossal facial
      coaptation. RESULTS: Various degrees of progressive paralysis were seen in 84
      (73%) cases. Sixty nine (60%) of the tumors involved multiple segments of the
      facial nerve. Sixty-two (53.9%) tumors involved the geniculate ganglion. Seventy
      four (64.3%) of the cases were schwannomas. Hearing preservation surgeries were
      performed in 60 (52.1%). Ninety one (79.1%) of the nerves that were sectioned in
      association with tumor removal were restituted primarily by interposition cable
      grafting. The mean preoperative House-Brackmann grading of the facial nerve was
      3.6. The mean immediate postoperative grading was 5.4, which recovered to a mean
      of 3.4 at the end of 1 yr. CONCLUSION: In patients with good facial nerve
      function (House-Brackmann grade I-II), a wait-and-scan approach is recommended.
      In cases where the facial nerve has been interrupted during surgery, the cable
      nerve interpositioning technique is a convenient and well-accepted procedure for
      immediate restitution of the nerve.

PMID- 29029276
TI  - Complement C3 Associates With Incidence of Diabetes, but No Evidence of a Causal
      Relationship.
AB  - Purpose: This study explored whether complement factor 3 (C3) in plasma is
      associated with incidence of diabetes in a population-based cohort. We also
      identified genetic variants related to C3 and explored whether C3 and diabetes
      share common genetic determinants. Methods: C3 was analyzed in plasma from 4368
      nondiabetic subjects, 46 to 68 years old, from the Malmo Diet and Cancer Study.
      Incidence of diabetes was studied in relationship to C3 levels during 17.7+/- 4.4
      years of follow-up. Genotypes associated with C3 were identified in a genome-wide
      association study. Diabetes Genetics Replication and Meta-Analysis and the
      European Genetic Database were used for in silico look-up. Results: In all, 538
      (12.3%) subjects developed diabetes during 18 years of follow-up. High C3 was
      significantly associated with incidence of diabetes after risk factor adjustments
      (hazard ratio comparing 4th vs 1st quartile, 1.54 (95% confidence interval, 1.13
      to 2.09; P = 0.005). C3 was associated with polymorphisms at the complement
      factor H locus (P < 10-8). However, no relationship with diabetes was observed
      for this locus. Another eight loci were associated with C3 with P < 10-5. One of
      them, the glucose kinase regulatory protein (GCKR) locus, has been previously
      associated with diabetes. The relationship between C3 levels and the GCKR locus
      was replicated in the European Genetic Database cohort. Conclusions: Plasma
      concentration of C3 is a risk marker for incidence of diabetes. The results
      suggest that this association could, in part, be explained by pleiotropic effects
      related to the GCKR gene.

PMID- 29029277
TI  - miR-122 Release in Exosomes Precedes Overt Tolvaptan-Induced Necrosis in a
      Primary Human Hepatocyte Micropatterned Coculture Model.
AB  - Idiosyncratic drug-induced liver injury (IDILI) is thought to often result from
      an adaptive immune attack on the liver. However, it has been proposed that the
      cascade of events culminating in an adaptive immune response begins with drug
      induced hepatocyte stress, release of exosomal danger signals, and innate immune
      activation, all of which may occur in the absence of significant hepatocelluar
      death. A micropatterned coculture model (HepatoPac) was used to explore the
      possibility that changes in exosome content precede overt necrosis in response to
      the IDILI drug tolvaptan. Hepatocytes from 3 human donors were exposed to a range
      of tolvaptan concentrations bracketing plasma Cmax or DMSO control continuously
      for 4, 24, or 72 h. Although alanine aminotransferase release was not
      significantly affected at any concentration, tolvaptan exposures at approximately
      30-fold median plasma Cmax resulted in increased release of exosomal microRNA-122
      (miR-122) into the medium. Cellular imaging and microarray analysis revealed that
      the most significant increases in exosomal miR-122 were associated with
      programmed cell death and small increases in membrane permeability. However,
      early increases in exosome miR-122 were more associated with mitochondrial
      induced apoptosis and oxidative stress. Taken together, these data suggest that
      tolvaptan treatment induces cellular stress and exosome release of miR-122 in
      primary human hepatocytes in the absence of overt necrosis, providing direct
      demonstration of this with a drug capable of causing IDILI. In susceptible
      individuals, these early events may occur at pharmacologic concentrations of
      tolvaptan and may promote an adaptive immune attack that ultimately results in
      clinically significant liver injury.

PMID- 29029279
TI  - Radical, Staged Approach to Extensive Posterior Fossa Pediatric Ependymoma: 3
      Dimensional Operative Video.

PMID- 29029278
TI  - Efficacy and safety of delafloxacin compared with vancomycin plus aztreonam for
      acute bacterial skin and skin structure infections: a Phase 3, double-blind,
      randomized study.
AB  - Background: Delafloxacin is an investigational anionic fluoroquinolone in
      development for oral or intravenous administration for the treatment of
      infections caused by Gram-positive (including MRSA), Gram-negative, atypical and
      anaerobic organisms. Objectives: To establish the non-inferiority of delafloxacin
      compared with vancomycin plus aztreonam for the treatment of acute bacterial skin
      and skin structure infections and to compare the safety of the two
      antimicrobials. Patients and methods: A Phase 3, multicentre, randomized, double
      blind, active-controlled study with 660 patients compared delafloxacin 300 mg or
      vancomycin 15 mg/kg plus aztreonam 2 g each administered twice daily
      intravenously for 5-14 days. Non-inferiority was evaluated by objective response
      (>=20% erythema reduction) at 48-72 h after initiation of study drug,
      investigator subjective assessment of outcome and microbiological responses.
      Clinical Trials Registration: NCT01811732. EudraCT number: 2012-001767-71.
      Results: In the ITT analysis set, the objective response was 78.2% in the
      delafloxacin arm and 80.9% in the vancomycin/aztreonam arm (mean treatment
      difference, -2.6%; 95% CI, -8.78% to 3.57%). Investigator-assessed cure was
      similar between the two groups at follow-up (52.0% versus 50.5%) and late follow
      up (70.4% versus 66.6%). Bacterial eradication of MRSA was 100% and 98.5% in the
      delafloxacin group and the vancomycin/aztreonam group, respectively. Frequency of
      treatment-emergent adverse events in the delafloxacin and vancomycin/aztreonam
      groups was similar. Treatment-emergent adverse events leading to study drug
      discontinuation were higher in the vancomycin/aztreonam group compared with the
      delafloxacin group (4.3% versus 0.9%). Conclusions: Delafloxacin, an anionic
      fluoroquinolone, was statistically non-inferior to vancomycin/aztreonam at 48-72
      h following the start of therapy and was well tolerated as monotherapy in the
      treatment of acute bacterial skin and skin structure infections.

PMID- 29029280
TI  - Pharmacokinetics and safety results from the Phase 3 randomized, open-label,
      study of intravenous posaconazole in patients at risk of invasive fungal disease.

PMID- 29029281
TI  - Rabies-what is necessary to achieve 'zero by 30'?

PMID- 29029282
TI  - Ecoinformatics Can Infer Causal Effects of Crop Variety on Insect Attack by
      Capitalizing on 'Pseudoexperiments' Created When Different Crop Varieties Are
      Interspersed: A Case Study in Almonds.
AB  - Capturing the complementary strengths of observational and experimental research
      methods usually requires the researcher to gather separate experimental and
      observational data sets. In some cases, however, commercial agricultural
      practices produce the spatial and temporal mixing of 'treatments' independently
      of other possibly covarying factors that is normally achieved only with formal
      experimentation. The resulting 'pseudoexperiments' can provide strong evidence
      for causal relationships. Here, we analyze a large observational data set that
      creates a series of such pseudoexperiments to assess the effect of different
      commercial varieties of almond, Prunus dulcis (Mill.) on the impact of two key
      lepidopteran pests, the navel orangeworm Amyelois transitella (Walker)
      (Lepidoptera: Pyralidae), and the peach twig borer Anarsia lineatella Zeller
      (Lepidoptera: Gelechiidae). Almonds are universally planted as polycultures of
      different varieties to obtain efficient cross-pollination. We find substantial
      differences across almond varieties in the rates of infestation of almond hulls
      and nutmeats by the two pests. We find no support for the hypothesis that earlier
      maturing varieties sustain higher attack; for A. transitella, later-maturing
      varieties instead had more frequent infestation. On many almond varieties, A.
      lineatella reaches high infestation levels by feeding almost exclusively on the
      hulls, rather than nutmeats. Given the importance of these pests in directly
      destroying almond nuts and in promoting aflatoxin-producing Aspergillus sp.
      fungal infections of almonds, further work exploring the impact of these pests is
      warranted. Because many crops requiring cross-pollination are planted as mixtures
      of different varieties, commercial agricultural production data hold great
      potential for studying within-crop variation in susceptibility to insect attack.

PMID- 29029284
TI  - The Influence of CO2 on Genioglossus Muscle After-Discharge Following Arousal
      From Sleep.
AB  - Objectives: Ventilatory after-discharge (sustained elevation of ventilation
      following stimulus removal) occurs during sleep but not when hypocapnia is
      present. Genioglossus after-discharge also occurs during sleep, but CO2 effects
      have not been assessed. The relevance is that postarousal after-discharge may
      protect against upper airway collapse. This study aimed to determine whether
      arousal elicits genioglossus after-discharge that persists into sleep, and
      whether it is influenced by CO2. Methods: Twenty-four healthy individuals (6
      female) slept with a nasal mask and ventilator. Sleep (EEG, EOG, EMG),
      ventilation (pneumotachograph), end-tidal CO2 (PETCO2), and intramuscular
      genioglossus EMG were monitored. NREM eucapnia was determined during 5 minutes on
      continuous positive airway pressure (4 cmH2O). Inspiratory pressure support was
      increased until PETCO2 was >=2 mm Hg below NREM eucapnia. Supplemental CO2 was
      added to reproduce normocapnia, without changing ventilator settings. Arousals
      were induced by auditory tones and genioglossus EMG compared during steady-state
      hypocapnia and normocapnia. Results: Eleven participants (4 female) provided
      data. Prearousal PETCO2 was less (p < .05) during hypocapnia (40.74 +/- 2.37)
      than normocapnia (43.82 +/- 2.89), with differences maintained postarousal. After
      discharge, defined as an increase in genioglossus activity above prearousal
      levels, occurred following the return to sleep. For tonic activity, after
      discharge lasted four breaths irrespective of CO2 condition. For peak activity,
      after-discharge lasted one breath during hypocapnia and 6 breaths during
      normocapnia. However, when peak activity following the return to sleep was
      compared between CO2 conditions no individual breath differences were observed.
      Conclusions: Postarousal genioglossal after-discharge may protect against upper
      airway collapse during sleep. Steady-state CO2 levels minimally influence
      postarousal genioglossus after-discharge.

PMID- 29029283
TI  - Trajectories of cardiorespiratory fitness in patients with juvenile
      dermatomyositis.
AB  - Objectives: Previous research demonstrated decreased cardiorespiratory fitness
      (CRF) in patients with JDM during active disease and remission. However,
      longitudinal data regarding trajectories of CRF are currently lacking. The
      objective of this study was to determine trajectories of CRF in patients with
      both monocyclic and chronic JDM, and to identify potential predictors of these
      trajectories. Methods: Thirty-six patients with JDM [median age (interquartile
      range) at diagnosis: 8.3 (6.3-15.4) years] treated in our paediatric rheumatology
      outpatient clinic were included. All patients performed multiple cardiopulmonary
      exercise tests between 2003 and 2016. Relevant CRF parameters were analysed,
      including peak oxygen uptake, maximal workload, mechanical efficacy and oxygen
      uptake at ventilatory anaerobic threshold. We analysed trajectories up to 10
      years after diagnosis and determined predictors of CRF outcome parameters by
      multilevel analyses. Results: Trajectories demonstrated significant declines in
      CRF during the active phase of the disease with subsequent improvement in CRF
      during the initial years after diagnosis. However, hereafter no further
      improvements, and even a decrease, in CRF were observed over time in both
      monocyclic and chronic subtypes of JDM. We found that a longer disease duration,
      younger age of onset and higher prednisone dose negatively influence CRF.
      Conclusion: Patients with both monocyclic and chronic JDM show decreases in long
      term CRF trajectories. Longer disease duration, younger age of onset and higher
      prednisone dose negatively influence CRF. This study stresses the need for
      regular evaluation of CRF and implementation of (exercise) interventions to
      improve CRF in patients with JDM, even in monocyclic patients.

PMID- 29029285
TI  - Selection of Reference Genes for Expression Studies in Diaphorina citri
      (Hemiptera: Liviidae).
AB  - The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae), is
      considered the main vector of the bacteria associated with huanglongbing, a very
      serious disease that has threatened the world citrus industry. The absence of
      efficient control management protocols, including a lack of resistant cultivars,
      has led to the development of different approaches to study this pathosystem. The
      production of resistant genotypes relies on D. citri gene expression analyses by
      RT-qPCR to assess control of the vector population. High-quality, reliable RT
      qPCR analyses depend upon proper reference gene selection and validation.
      However, adequate D. citri reference genes have not yet been identified. In the
      present study, we evaluated the genes EF 1-alpha, ACT, GAPDH, RPL7, RPL17, and
      TUB as candidate reference genes for this insect. Gene expression stability was
      evaluated using the mathematical algorithms deltaCt, NormFinder, BestKeeper, and
      geNorm, at five insect developmental stages, grown on two different plant hosts
      [Citrus sinensis (L.) Osbeck (Sapindales: Rutaceae) and Murraya paniculata (L.)
      Jack (Sapindales: Rutaceae)]. The final gene ranking was calculated using
      RefFinder software, and the V-ATPase-A gene was selected for validation.
      According to our results, two reference genes are recommended when different
      plant hosts and developmental stages are considered. Considering gene expression
      studies in D. citri grown on M. paniculata, regardless of the insect
      developmental stage, GAPDH and RPL7 have the best fit as reference genes in RT
      qPCR analyses, whereas GAPDH and EF 1-alpha are recommended as reference genes in
      insect studies using C. sinensis.

PMID- 29029286
TI  - Patterns of Abundance and Host Specificity of Bat Ectoparasites in the Central
      Balkans.
AB  - Bats are hosts to a number of ectoparasites-acarines (ticks, chiggers, other
      mites), bat flies, and fleas. Bat ectoparasites might have significant ecological
      and public health importance as they may be potential vectors of zoonotic agents.
      It is important to identify their distribution, diversity, and host-parasite
      associations. Bat ectoparasites in the central Balkans have been largely
      understudied. The present research was conducted in 45 localities at the
      territory of Bosnia and Herzegovina, former Yugoslav Republic of Macedonia,
      Montenegro, and Serbia. In total, 1,143 individuals of 18 species of bats have
      been examined for the presence and abundance of ectoparasite species during 3 yr
      of research. In total, 21 ectoparasite species have been identified: three
      species of ticks, seven species of mites (including one species of chigger),
      eight species of bat flies, and three species of fleas. In total, 80 host
      parasite associations have been identified. The largest number of ectoparasites
      parasitized primarily only one host species. The highest total number of hosts
      was identified for ectoparasite species Ixodes vespertilionis Koch, Nycteribia
      schmidlii Schiner, and Spinturnix myoti Kolenati. The spinturnicid mite
      Spinturnix psi Kolenati was the most abundant ectoparasite species and together
      with Penicilidia dufouri Westwood the most widely distributed species of bat
      ectoparasite, being present at 21 localities in the central Balkans. The
      presented data include the first systematic records of patterns of prevalence,
      mean intensity, mean abundance, and host specificity for bat ectoparasites in the
      central Balkans.

PMID- 29029288
TI  - Microsurgical Clipping of a Blister-like Basilar Tip Aneurysm: 2-Dimensional
      Operative Video.

PMID- 29029287
TI  - Survival in Response to Multimodal Therapy in Anaplastic Thyroid Cancer.
AB  - Context: Historical outcomes in anaplastic thyroid cancer (ATC) have been dismal.
      Objective: To determine whether an initial intensive multimodal therapy (MMT) is
      associated with improved ATC survival. Design: MMT was offered to all patients
      with newly diagnosed ATC treated at the Mayo Clinic from 2003 through 2015; MMT
      vs care with palliative intent (PI) was individualized considering clinical
      status and patient preferences. Outcomes were retrospectively analyzed by
      American Joint Committee on Cancer stage and treatments compared with patient
      cohort data from 1949 through 1999. Patients: Forty-eight patients (60% male;
      median age, 62 years); 18 treated with PI, 30 with MMT. Main Outcome Measure:
      Overall survival (OS) and progression-free survival determined by Kaplan-Meier
      method. Results: Median OS and 1-year survival for the later cohort were 9 months
      [95% confidence interval (CI), 4 to 22 months] and 42% (95% CI, 28% to 56%) vs 3
      months and 10% for the earlier cohort. Median OS was 21 months compared with 3.9
      months in the pooled MMT vs PI groups for the later cohort [hazard ratio (HR),
      0.32; P = 0.0006]. Among only patients in the later cohort who had stage IVB
      disease, median OS was 22.4 vs 4 months (HR, 0.12; 95% CI, 0.03 to 0.44; P =
      0.0001), with 68% vs 0% alive at 1 year (MMT vs PI). Among patients with stage
      IVC cancer, OS did not differ by therapy. Conclusion: MMT appears to convey
      longer survival in ATC among patients with stage IVA/B disease.

PMID- 29029289
TI  - Post-Traumatic Hydrocephalus in Children: A Retrospective Study in 42 Pediatric
      Hospitals Using the Pediatric Health Information System.
AB  - BACKGROUND: Post-traumatic hydrocephalus (PTH) is a potentially treatable cause
      of poor recovery from traumatic brain injury (TBI) that remains poorly
      understood, particularly among children. OBJECTIVE: To better understand the risk
      factors for pediatric PTH using a large, multi-institutional database. METHODS:
      We conducted a retrospective cohort study using administrative data from 42
      pediatric hospitals participating in the Pediatric Health Information System. All
      patients <=21 yr surviving a hospitalization with an International Classification
      of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for TBI were
      identified. The primary outcome was PTH, defined by an ICD-9-CM procedure code
      for surgical management of hydrocephalus within 6 mo. Data were analyzed using
      multivariable logistic regression. RESULTS: We identified 91 583 patients <=21 yr
      with TBI, 846 of whom developed PTH. Odds of PTH were significantly higher in
      children <1 yr compared to older age groups. A total of 48.7% of PTH cases were
      victims of abuse (adjusted odds ratio [aOR] 2.62, 95% confidence interval [CI]
      2.16-3.18). PTH was more common after craniotomy (aOR 1.60, 95% CI 1.30-1.97).
      Craniectomy without early cranioplasty was associated with markedly increased
      odds of PTH (aOR 3.67, 95% CI 2.66-5.07), an effect not seen in those undergoing
      cranioplasty within 30 d (aOR 1.19, 95% CI 0.75-1.89). CONCLUSION: PTH was seen
      in 0.9% of children who sustained a TBI and was more common in those <1 yr.
      Severe injury, abuse, and craniectomy with delayed cranioplasty were associated
      with greatly increased likelihood of PTH. Early cranioplasty in children who
      require craniectomy may reduce the risk for PTH.

PMID- 29029290
TI  - NMDA Receptor-mediated Ca2+ Influx in the Absence of Mg2+ Block Disrupts Rest:
      Activity Rhythms in Drosophila.
AB  - Study Objectives: The correlated activation of pre- and postsynaptic neurons is
      essential for the NMDA receptor-mediated Ca2+ influx by removing Mg2+ from block
      site and NMDA receptors have been implicated in phase resetting of circadian
      clocks. So we assessed rest:activity rhythms in Mg2+ block defective animals.
      Methods: Using Drosophila locomotor monitoring system, we checked circadian
      rest:activity rhythms of different mutants under constant darkness (DD) and
      light:dark (LD) conditions. We recorded NMDA receptor-mediated currents or Ca2+
      increase in neurons using patch-clamp and Ca2+ imaging techniques. Results: We
      found that Mg2+ block defective mutant flies were completely arrhythmic under DD.
      To further understand the role of Mg2+ block in daily circadian rest:activity, we
      observed the mutant files under LD cycles, and we found severely reduced morning
      anticipation and advanced evening peak compared to control flies. We also used
      tissue-specific expression of Mg2+ block defective NMDA receptors and
      demonstrated pigment-dispersing factor receptor (PDFR)-expressing circadian
      neurons were implicated in mediating the circadian rest:activity deficits.
      Endogenous functional NMDA receptors are expressed in most Drosophila neurons,
      including in a subgroup of dorsal neurons (DN1s). Subsequently, we determined
      that the uncorrelated extra Ca2+ influx may act in part through Ca2+/Calmodulin
      (CaM)-stimulated PDE1c pathway leading to morning behavior phenotypes.
      Conclusions: These results demonstrate that Mg2+ block of NMDA receptors at
      resting potential is essential for the daily circadian rest:activity rhythms and
      we propose that Mg2+ block functions to suppress CaM-stimulated PDE1c activation
      at resting potential, thus regulating Ca2+ and cyclic AMP oscillations in
      circadian and sleep circuits.

PMID- 29029292
TI  - Minimizing Retraction by Pia-Arachnoidal 10-0 Sutures in Intrasulcal Dissection.
AB  - BACKGROUND: In contemporary microneurosurgery reducing retraction-induced injury
      to the brain is essential. Self-retaining retractor systems are commonly used to
      improve visualization and decrease the repetitive microtrauma, but sometimes self
      retaining retractor systems can be cumbersome and the force applied can cause
      focal ischemia or contusions. This may increase the morbidity and mortality.
      Here, we describe a technique of retraction using 10-0 sutures in the arachnoid.
      OBJECTIVE: To evaluate the imaging and clinical results in patients where 10-0
      suture retraction was used to aid the surgical procedure. METHODS: Adjacent
      cortex was retracted by placing 10-0 nylon suture in the arachnoid of the bank or
      banks of the sulcus. The suture was secured to the adjacent dural edge by using
      aneurysm clips, allowing for easy adjustability of the amount of retraction. We
      retrospectively analyzed the neurological outcome, signal changes in
      postoperative imaging, and ease of performing surgery in 31 patients with various
      intracranial lesions including intracranial aneurysms, intra- and extra-axial
      tumors, and cerebral ischemia requiring arterial bypass. RESULTS: Clinically,
      there were no injuries, vascular events, or neurological deficits referable to
      the relevant cortex. Postoperative imaging did not show changes consistent with
      ischemia or contusion due to the retraction. This technique improved the
      visualization and illumination of the surgical field in all cases. CONCLUSION:
      Retraction of the arachnoid can be used safely in cases where trans-sulcal
      dissection is required. This technique may improve initial visualization and
      decrease the need for dynamic or static retraction.

PMID- 29029291
TI  - Nutrition Influences Caffeine-Mediated Sleep Loss in Drosophila.
AB  - Study objectives: Plant-derived caffeine is regarded as a defensive compound
      produced to prevent herbivory. Caffeine is generally repellent to insects and
      often used to study the neurological basis for aversive responses in the model
      insect, Drosophila melanogaster. Caffeine is also studied for its stimulatory
      properties where sleep or drowsiness is suppressed across a range of species.
      Since limiting access to food also inhibits fly sleep-an effect known as
      starvation-induced sleep suppression-we tested whether aversion to caffeinated
      food results in reduced nutrient intake and assessed how this might influence fly
      studies on the stimulatory effects of caffeine. Methods: We measured sleep and
      total consumption during the first 24 hours of exposure to caffeinated diets
      containing a range of sucrose concentrations to determine the relative influence
      of caffeine and nutrient ingestion on sleep. Experiments were replicated using
      three fly strains. Results: Caffeine reduced total consumption and nighttime
      sleep, but only at intermediate sucrose concentrations. Although sleep can be
      modeled by an exponential dose response to nutrient intake, caffeine-mediated
      sleep loss cannot be explained by absolute caffeine or sucrose ingestion alone.
      Instead, reduced sleep strongly correlates with changes in total consumption due
      to caffeine. Other bitter compounds phenocopy the effect of caffeine on sleep and
      food intake. Conclusions: Our results suggest that a major effect of dietary
      caffeine is on fly feeding behavior. Changes in feeding behavior may drive
      caffeine-mediated sleep loss. Future studies using psychoactive compounds should
      consider the potential impact of nutrition when investigating effects on sleep.

PMID- 29029293
TI  - Multiple Chronic Conditions in Spousal Caregivers of Older Adults With Functional
      Disability: Associations With Caregiving Difficulties and Gains.
AB  - Objectives: Multiple chronic conditions (MCCs) are common and have harmful
      consequences in later life. Along with managing their own health, many aging
      adults care for an impaired partner. Spousal caregiving may be more stressful
      when caregivers have MCCs, particularly those involving complex management. Yet,
      little is known about combinations of conditions that are most consequential for
      caregiving outcomes. Method: Using a U.S. sample of 359 spousal caregivers and
      care recipients from the 2011 National Aging Trends Study and National Study of
      Caregiving, we examined three categories of MCCs based on similarity of
      management strategies (concordant only, discordant only, and both concordant and
      discordant) and their associations with caregiving difficulties and gains. We
      also considered gender differences. Results: Relative to caregivers without MCCs,
      caregivers with discordant MCCs reported fewer gains, whereas caregivers with
      both concordant and discordant MCCs reported greater emotional and physical
      difficulties. Wives with discordant MCCs only reported a trend for greater
      physical difficulties. Caregivers with concordant MCCs did not report more
      difficulties or gains. Discussion: Spousal caregivers with MCCs involving
      discordant management strategies appear to be at risk for adverse care-related
      outcomes and may benefit from support in maintaining their own health as well as
      their caregiving responsibilities.

PMID- 29029294
TI  - Cardiovascular events in anti-neutrophil cytoplasmic antibody-associated
      vasculitis: a meta-analysis of observational studies.
AB  - Objectives: Several chronic inflammatory diseases are associated with
      cardiovascular disease, but the risk in ANCA-associated vasculitis is poorly
      quantified. The aim of the present study was to review the evidence for an
      increased cardiovascular risk, including ischaemic heart disease, cerebrovascular
      accidents and peripheral arterial disease, in patients with ANCA-associated
      vasculitis. Methods: A comprehensive systematic review was conducted in
      accordance with guidelines of preferred reporting items for systematic reviews
      and meta-analyses. The databases PubMed, Embase.com and the Cochrane Library
      (Wiley) were searched for original observational studies comparing vasculitis
      patients with at least one control group. Summary estimates were derived with a
      random-effects model and reported as relative risks. Results: One thousand three
      hundred and seventy-five studies were identified. Seven studies were included,
      comprising almost 14 000 ANCA-associated vasculitis patients vs general
      population controls in six studies and chronic kidney disease patients in one
      study. ANCA-associated vasculitis carried a relative risk of 1.65 (95% CI: 1.23,
      2.22) for all cardiovascular events, 1.60 (95% CI: 1.39, 1.84) for ischaemic
      heart disease and 1.20 (95% CI: 0.98, 1.48) for cerebrovascular accidents. We did
      not find studies that addressed the risk for peripheral arterial disease
      separately. No heterogeneity was seen in the estimates. Conclusion: This meta
      analysis of observational studies supports an increase in cardiovascular risk in
      patients with ANCA-associated vasculitis of ~65%, similar to that found in other
      chronic inflammatory diseases. Hence, there is a clear need for active
      cardiovascular risk management in patients with ANCA-associated vasculitis.

PMID- 29029295
TI  - Probabilistic Distances Between Trees.
AB  - Most existing measures of distance between phylogenetic trees are based on the
      geometry or topology of the trees. Instead, we consider distance measures which
      are based on the underlying probability distributions on genetic sequence data
      induced by trees. Monte Carlo schemes are necessary to calculate these distances
      approximately, and we describe efficient sampling procedures. Key features of the
      distances are the ability to include substitution model parameters and to handle
      trees with different taxon sets in a principled way. We demonstrate some of the
      properties of these new distance measures and compare them to existing distances,
      in particular by applying multidimensional scaling to data sets previously
      reported as containing phylogenetic islands. [Metric; probability distribution;
      multidimensional scaling; information geometry.

PMID- 29029296
TI  - The British Society for Rheumatology guideline for the management of systemic
      lupus erythematosus in adults: Executive Summary.

PMID- 29029297
TI  - Cytomegalovirus-Specific T-Cell Transfer for Refractory Cytomegalovirus Infection
      After Haploidentical Stem Cell Transplantation: The Quantitative and Qualitative
      Immune Recovery for Cytomegalovirus.
AB  - Background: The efficiency and mechanisms of adoptive transfer of cytomegalovirus
      (CMV)specific T cells for refractory CMV infection after haploidentical stem cell
      transplantation (haplo-SCT) remain largely unknown. Methods: Thirty-two patients
      with refractory CMV infection who accepted treatment with adoptive CMV-specific T
      cell infusion following haplo-SCT were prospectively enrolled. Another 32
      patients with nonrefractory CMV infection after haplo-SCT were selected as
      control subjects. The phenotypical and functional characteristics of CMV-specific
      T cells were analyzed before and after cellular therapy in the refractory cohort,
      as well as in the nonrefractory cohort. Results: In the refractory cohort, 27 of
      the 32 treated patients exhibited CMV clearance within 4 weeks after adoptive T
      cell transfer without recurrence. The in vivo expansion of CMV-specific T cells
      and improvements in the cytokine production and proliferation ability of the CMV
      specific T cells were observed after cellular therapy. Moreover, a reduced
      expression of programmed death-1 (PD-1) on CMV-specific T cells was observed.
      However, in the remaining 5 patients who showed CMV recurrence 4 weeks after
      transfer, neither the quantity nor the function of CMV-specific T cells was
      restored. Conclusions: The adoptive transfer of CMV-specific T cells promotes
      quantitative and functional recovery of CMV-specific T cells to guard against
      refractory CMV infection after haplo-SCT.

PMID- 29029298
TI  - The Effect of Larval Diet on Adult Survival, Swarming Activity and Copulation
      Success in Male Aedes aegypti (Diptera: Culicidae).
AB  - Control of Aedes aegypti (L.) (Diptera: Culicidae) populations is vital for
      reducing the transmission of several pervasive human diseases. The success of new
      vector control technologies will be influenced by the fitness of laboratory
      reared transgenic males. However, there has been relatively little published data
      on how rearing practices influence male fitness in Aedes mosquitoes. In the
      laboratory, the effect of larval food availability on adult male fitness was
      tested, using a range of different fitness measures. Larval food availability was
      demonstrated to be positively correlated with adult body size. Larger males
      survived longer and exhibited greater swarming activity. As a consequence, larger
      males may have more mating opportunities in the wild. However, we also found that
      within a swarm larger males did not have an increased likelihood of copulating
      with a female. The outcome of the mating competition experiments depended on the
      methodology used to mark the males. These results show that fitness assessment
      can vary depending on the measure analyzed, and the methodology used to determine
      it. Continued investigation into these fitness measures and methodologies, and
      critically, their utility for predicting male performance in the field, will
      increase the efficiency of vector control programs.

PMID- 29029299
TI  - Weak Regulation of Many Targets Is Cumulatively Powerful-An Evolutionary
      Perspective on microRNA Functionality.
AB  - Why do microRNAs (miRNAs) weakly repress so many targets such that most targets
      do not have phenotypic effects? An increasingly accepted view posits that weak
      targeting has no biological function and each miRNA effectively has only a few
      functional targets. Here, we review the evolutionary arguments for this postulate
      and find these arguments seriously flawed. In contrast, from the systems
      perspective, the power of broad and weak targeting may reside in the cumulative
      effects of all repressions, which collectively stabilize gene regulatory
      networks. This view predicts that miRNAs would show little tendency to downsize
      their target pools. A survey of "twin-miRs" production indeed validates this
      prediction.

PMID- 29029300
TI  - Flight Activity and Field Infestation Relationships for Coffee Berry Borer in
      Commercial Coffee Plantations in Kona and Kau Districts, Hawaii.
AB  - The coffee berry borer (CBB), Hypothenemus hampei Ferrari (Coleoptera:
      Curculionidae: Scolytinae) is a recent invader to Hawaii. To date, limited
      information regarding the seasonal phenology of this pest on the islands limits
      the implementation of integrated control strategies. As part of a coffee farmer
      training program, we monitored CBB flight activity in 15 coffee plantations (Kona
      and Kau Districts) over 10 mo with methanol-ethanol (3:1 ratio) baited traps.
      Concurrently, we quantified CBB infestation and penetration rates inside
      developing coffee berries through the end of harvest. Approximately 1 million CBB
      were captured, with the highest activity (e.g., >500 CBB/trap/wk) in December
      through February, coinciding with end of main regional harvesting periods.
      Relatively high activity (>250 CBB/trap/wk) was also observed during berry
      development, in May and June (Kona) and June and July (Kau). Field infestation
      rates were higher overall in Kau (9.6 +/- 1.1%) compared with coffee plantations
      in Kona (4.7 +/- 0.4%). Linear regression investigated relationships between CBB
      trap data and berry infestation rates. Trap catch data generally correlated
      better with the proportion of shallow entries (AB position) compared with deeper
      penetrations (CD position) or total infestation. Pearson correlation coefficients
      based on different parameters (i.e., region, altitude, and berry phenology)
      revealed positive and mostly significant correlations between these variables (R
      values 0.410 to 0.837). Timing peak flight activity of CBB with insecticide
      applications will help coffee growers improve pest control. The ability of trap
      data to calculate reliable economic (action) thresholds for the CBB is discussed.

PMID- 29029301
TI  - Attractiveness of Host Plants at Different Growth Stage to Kudzu Bug, Megacopta
      cribraria (Heteroptera: Plataspidae): Behavioral Responses to Whole Plant and
      Constitutive Volatiles.
AB  - The kudzu bug, Megacopta cribraria (Fabricius), is an invasive pest of soybeans,
      Glycine max (L.) Merr., that has recently been detected in the United States.
      This study investigated whether there was a differential attraction of adult bugs
      to soybean growth stages, and whether the attraction was related to soybean
      constitutive volatiles. Greenhouse choice assays examined the behavioral
      orientation preference of adult bugs exposed to four growth stages of whole
      soybean plants: vegetative (V2), flowering (R1), pod (R3), and seed (R5). Results
      show that significantly more adults landed on plants in the early reproductive
      stage R1 than in other stages. Laboratory olfactometer assays also demonstrate
      that significantly more adult bugs were attracted to R1 plants, with females
      responding more strongly than males. Both greenhouse and olfactometer assays
      indicate that the differential attraction of adult bugs to soybean growth stages
      was mediated by plant constitutive volatiles. These results offer an insight into
      kudzu bug chemical and behavioral ecology and thus are of great significance for
      optimizing the timing of field scouting and treatment as well as the development
      of soybean pest management programs.

PMID- 29029303
TI  - Clinical Usage of the Adjuvanted Herpes Zoster Subunit Vaccine (HZ/su):
      Revaccination of Recipients of Live Attenuated Zoster Vaccine and
      Coadministration With a Seasonal Influenza Vaccine.

PMID- 29029304
TI  - Conventional and Advanced Imaging of Spine Oncologic Disease, Nonoperative Post
      treatment Effects, and Unique Spinal Conditions.
AB  - In this review, we discuss the imaging features of diseases and conditions
      ranging from neoplastic to nonoperative post-treatment effects to unique
      conditions of the spine. Additionally, advanced imaging may increase diagnostic
      certainty in cases where conventional imaging characteristics of benign lesions
      and malignant pathology are variable.

PMID- 29029302
TI  - Acute Kynurenine Challenge Disrupts Sleep-Wake Architecture and Impairs
      Contextual Memory in Adult Rats.
AB  - Study Objectives: Tryptophan metabolism via the kynurenine pathway may represent
      a key molecular link between sleep loss and cognitive dysfunction. Modest
      increases in the kynurenine pathway metabolite kynurenic acid (KYNA), which acts
      as an antagonist at N-methyl-d-aspartate and alpha7 nicotinic acetylcholine
      receptors in the brain, result in cognitive impairments. As glutamatergic and
      cholinergic neurotransmissions are critically involved in modulation of sleep,
      our current experiments tested the hypothesis that elevated KYNA adversely
      impacts sleep quality. Methods: Adult male Wistar rats were treated with vehicle
      (saline) and kynurenine (25, 50, 100, and 250 mg/kg), the direct bioprecursor of
      KYNA, intraperitoneally at zeitgeber time (ZT) 0 to rapidly increase brain KYNA.
      Levels of KYNA in the brainstem, cortex, and hippocampus were determined at ZT 0,
      ZT 2, and ZT 4, respectively. Analyses of vigilance state-related parameters
      categorized as wake, rapid eye movement (REM), and non-REM (NREM) as well as
      spectra power analysis during NREM and REM were assessed during the light phase.
      Separate animals were tested in the passive avoidance paradigm, testing
      contextual memory. Results: When KYNA levels were elevated in the brain, total
      REM duration was reduced and total wake duration was increased. REM and wake
      architecture, assessed as number of vigilance state bouts and average duration of
      each bout, and theta power during REM were significantly impacted. Kynurenine
      challenge impaired performance in the hippocampal-dependent contextual memory
      task. Conclusions: Our results introduce kynurenine pathway metabolism and
      formation of KYNA as a novel molecular target contributing to sleep disruptions
      and cognitive impairments.

PMID- 29029306
TI  - An Assessment of Phylogenetic Tools for Analyzing the Interplay Between
      Interspecific Interactions and Phenotypic Evolution.
AB  - Much ecological and evolutionary theory predicts that interspecific interactions
      often drive phenotypic diversification and that species phenotypes in turn
      influence species interactions. Several phylogenetic comparative methods have
      been developed to assess the importance of such processes in nature; however, the
      statistical properties of these methods have gone largely untested. Focusing
      mainly on scenarios of competition between closely-related species, we assess the
      performance of available comparative approaches for analyzing the interplay
      between interspecific interactions and species phenotypes. We find that many
      currently used statistical methods often fail to detect the impact of
      interspecific interactions on trait evolution, that sister-taxa analyses are
      particularly unreliable in general, and that recently developed process-based
      models have more satisfactory statistical properties. Methods for detecting
      predictors of species interactions are generally more reliable than methods for
      detecting character displacement. In weighing the strengths and weaknesses of
      different approaches, we hope to provide a clear guide for empiricists testing
      hypotheses about the reciprocal effect of interspecific interactions and species
      phenotypes and to inspire further development of process-based models.

PMID- 29029305
TI  - Large-Scale Automated Sleep Staging.
AB  - Study Objectives: Automated sleep staging has been previously limited by a
      combination of clinical and physiological heterogeneity. Both factors are in
      principle addressable with large data sets that enable robust calibration.
      However, the impact of sample size remains uncertain. The objectives are to
      investigate the extent to which machine learning methods can approximate the
      performance of human scorers when supplied with sufficient training cases and to
      investigate how staging performance depends on the number of training patients,
      contextual information, model complexity, and imbalance between sleep stage
      proportions. Methods: A total of 102 features were extracted from six
      electroencephalography (EEG) channels in routine polysomnography. Two thousand
      nights were partitioned into equal (n = 1000) training and testing sets for
      validation. We used epoch-by-epoch Cohen's kappa statistics to measure the
      agreement between classifier output and human scorer according to American
      Academy of Sleep Medicine scoring criteria. Results: Epoch-by-epoch Cohen's kappa
      improved with increasing training EEG recordings until saturation occurred (n =
      ~300). The kappa value was further improved by accounting for contextual
      (temporal) information, increasing model complexity, and adjusting the model
      training procedure to account for the imbalance of stage proportions. The final
      kappa on the testing set was 0.68. Testing on more EEG recordings leads to kappa
      estimates with lower variance. Conclusion: Training with a large data set enables
      automated sleep staging that compares favorably with human scorers. Because
      testing was performed on a large and heterogeneous data set, the performance
      estimate has low variance and is likely to generalize broadly.

PMID- 29029307
TI  - Droplet Digital PCR Diagnosis of Human Schistosomiasis: Parasite Cell-Free DNA
      Detection in Diverse Clinical Samples.
AB  - Background: Schistosomiasis japonica remains a major public health and
      socioeconomic concern in Southeast Asia. Sensitive and accurate diagnostics can
      play a pivotal role in achieving disease elimination goals. Methods: We
      previously reported a novel droplet digital polymerase chain reaction (ddPCR)
      assay targeting the mitochondrial gene nad1 to diagnose schistosomiasis japonica.
      The tool identified both prepatent and patent infections using Schistosoma
      japonicum DNA isolated from serum, urine, salivary glands, and feces in a murine
      model. The assay was validated here using clinical samples collected from 412
      subjects resident in an area moderately endemic for schistosomiasis in the
      Philippines. Results: S. japonicum DNA present in human stool, serum, urine, and
      saliva was detected quantitatively with high sensitivity. The capability to
      diagnose cases of human schistosomiasis using noninvasively collected clinical
      samples, the higher level of sensitivity obtained compared with the microscopy
      based Kato-Katz test, and the capacity to quantify infection intensity have
      important public health implications for schistosomiasis control and programs
      targeting other neglected tropical diseases. Conclusions: This verified ddPCR
      method represents a valuable new tool for the diagnosis and surveillance of
      schistosomiasis, particularly in low-prevalence and low-intensity areas
      approaching elimination and in monitoring where disease emergence or re-emergence
      is a concern.

PMID- 29029308
TI  - Difficult-to-treat rheumatoid arthritis: an area of unmet clinical need.
AB  - Increased effectiveness of pharmacological treatments in early RA has led many to
      believe that difficult-to-treat, established RA is a condition of the past.
      However, there are still plenty of RA patients who continue to have signs and
      symptoms suggestive of inflammatory disease activity, despite consecutive
      treatment with multiple conventional synthetic and biological DMARDs. We argue
      that difficult-to-treat RA constitutes an area of unmet clinical need and propose
      a definition of this concept. An overview of what is known about the multiple
      contributory factors varying for each individual patient, and an approach towards
      improved patient-tailored management are presented. This management approach
      involves thorough assessment to determine whether persistence of signs and
      symptoms is based on inflammatory disease activity, and the role of
      comorbidities. Furthermore, it addresses medication-related issues, such as non
      adherence, patient beliefs and expectations, and setting of realistic treatment
      goals.

PMID- 29029309
TI  - Limited Efficacy of Caffeine and Recovery Costs During and Following 5 Days of
      Chronic Sleep Restriction.
AB  - Objectives: To investigate the effects of caffeine on psychomotor vigilance and
      sleepiness during sleep restriction and following subsequent recovery sleep.
      Methods: Participants were N = 48 healthy good sleepers. All participants
      underwent five nights of sleep satiation (time-in-bed [TIB]: 10 hours), followed
      by five nights of sleep restriction (TIB: 5 hours), and three nights of recovery
      sleep (TIB: 8 hours) in a sleep laboratory. Caffeine (200 mg) or placebo was
      administered in the form of chewing gum at 08:00 am and 12:00 pm each day during
      the sleep restriction phase. Participants completed hourly 10-minute psychomotor
      vigilance tests and a modified Maintenance of Wakefulness Test approximately
      every 4 hours during the sleep restriction and recovery phases. Results: Caffeine
      maintained objective alertness compared to placebo across the first 3 days of
      sleep restriction, but this effect was no longer evident by the fourth day. A
      similar pattern of results was found for Maintenance of Wakefulness Test sleep
      latencies, such that those in the caffeine group (compared to placebo) did not
      show maintenance of wakefulness relative to baseline after the second night of
      restriction. Compared to placebo, participants in the caffeine condition
      displayed slower return to baseline in alertness and wakefulness across the
      recovery sleep period. Finally, the caffeine group showed greater N3 sleep
      duration during recovery. Conclusions: Caffeine appears to have limited efficacy
      for maintaining alertness and wakefulness across 5 days of sleep restriction.
      Perhaps more importantly, there may be recovery costs associated with caffeine
      use following conditions of prolonged sleep loss.

PMID- 29029310
TI  - Editor's Highlight: Fragrance Allergens Linalool and Limonene Allylic
      Hydroperoxides in Skin Allergy: Mechanisms of Action Focusing on Transcription
      Factor Nrf2.
AB  - Allergic contact dermatitis is regarded as the most frequent expression of
      immunotoxicity in humans. Many odorant terpenes commonly used in fragrance
      compositions are considered as weak skin sensitizers, whereas some of their
      autoxidation products, allylic hydroperoxides, are classified as strong
      sensitizers according to the local lymph node assay. However, the mechanism of
      their effects on the immune system remains unclear. Since dendritic cells play a
      key role in allergic contact dermatitis, we studied their activation by the
      frequently used linalool (LINA) and limonene (LIMO), and their respective
      sensitizing allylic hydroperoxides (LINA-OOH, LIMO-OOH). The THP-1 cell-line was
      used as a surrogate for dendritic cells, the model currently employed in the
      validated h-CLAT in vitro test. Our data showed that allylic hydroperoxides
      behave differently. Both LINA-OOH and LIMO-OOH oxidized cell surface thiols 30
      min after stimulation. However, the oxidative stress induced by LINA-OOH was
      stronger, with a higher decreased GSH/GSSG ratio and a stronger reactive species
      production. Moreover, LINA-OOH induced a stronger Nrf2 accumulation in
      correlation with nqo1 and ho-1 gene expression, 2 Nrf2 target genes. Regarding
      signaling pathways involved in these effects, P38 mitogen-activated protein
      kinase and P-ERK were activated in response to LINA-OOH but not with LIMO-OOH.
      CD54 and CD86 were induced 24-h postexposure. In contrast, LINA and LIMO did not
      modify THP-1 phenotype. This work underlies that autoxidation forming allylic
      hydroperoxide (ROOH) does not lead to equal chemical reactivity since LINA-OOH
      appears to be a stronger activator than LIMO-OOH, in regard to oxidative stress
      and Nrf2 pathway activation.

PMID- 29029311
TI  - Use of colchicine in pregnancy: a systematic review and meta-analysis.
AB  - Objectives: Colchicine is an anti-inflammatory agent used in the treatment of
      several rheumatological conditions. The use of colchicine in pregnancy is
      controversial. The current study aimed to systematically review and meta-analyse
      the existing data in the literature regarding the safety of colchicine in
      pregnancy. Methods: A systematic review was carried out using six electronic
      databases, identifying all relevant studies where colchicine was administered to
      pregnant women, and where pregnancy-related outcomes were measured. The primary
      endpoints were miscarriage and major foetal malformation. Secondary endpoints
      included birthweight and gestational age at birth. Results: Four studies were
      included for meta-analysis. Use of colchicine throughout pregnancy was not
      associated with an increased incidence of miscarriage or major foetal
      malformations. The incidence of miscarriage was significantly lower in women who
      took colchicine compared with those that did not. In women with FMF who took
      colchicine throughout the pregnancy, there was no significant difference in
      birthweight or gestational age compared with those who did not take colchicine.
      When not limited to FMF, colchicine use was associated with a significantly lower
      birthweight and gestational age compared with a control group including healthy
      women who did not take colchicine. Conclusions: Colchicine therapy did not
      significantly increase the incidence of foetal malformations or miscarriage when
      taken during pregnancy. Colchicine therapy for FMF should not be withheld on this
      basis during pregnancy.

PMID- 29029312
TI  - Prefusion F, Postfusion F, G Antibodies, and Disease Severity in Infants and
      Young Children With Acute Respiratory Syncytial Virus Infection.
AB  - Background: Respiratory syncytial virus (RSV) is the most frequent cause of lower
      respiratory tract infection in infants. Maternally derived RSV-specific
      antibodies play a role in protection against RSV infection in early life, but
      data regarding the concentration and specificity of those antibodies are
      incomplete. Methods: We prospectively enrolled a cohort of previously healthy
      infants and young children hospitalized (n = 45) or evaluated as outpatients (n =
      20) for RSV infection, and healthy noninfected age-matched controls (n = 18).
      Serum samples were obtained at enrollment to quantify the concentrations and
      neutralizing activity of serum immunoglobulin G antibodies to the RSV prefusion
      (pre-F), postfusion (post-F), and G glycoproteins. We also assessed the
      associations between antibody concentrations and clinical disease severity.
      Results: Concentrations of pre-F antibodies were >=3-fold higher than post-F
      antibodies and >30-fold higher than G antibodies in serum from infants with acute
      RSV infection. Antibody concentrations and neutralizing activity inversely
      correlated with age. The pre-F antibodies displayed the greatest neutralizing
      activity (55%-100%), followed by G (0%-45%), and post-F (0%-29%) antibodies.
      Higher concentrations of pre-F and G antibodies, but not post-F antibodies, were
      associated with lower clinical disease severity scores. Conclusions: Maternal
      antibodies directed to pre-F, followed by antibodies directed to G, can modulate
      RSV disease severity in young infants.

PMID- 29029314
TI  - Small Aneurysms Account for the Majority and Increasing Percentage of Aneurysmal
      Subarachnoid Hemorrhage: A 25-Year, Single Institution Study.
AB  - BACKGROUND: Prospective studies of unruptured aneurysms have shown very low rates
      of rupture for small aneurysms (<10 mm) and suggested that the risk of treatment
      outweighs benefit. However, common clinical practice shows that patients with
      aneurysmal subarachnoid hemorrhage (aSAH) frequently have small aneurysms.
      OBJECTIVE: To investigate trends in size and location of ruptured aneurysms over
      a 25-yr period. METHODS: A prospective, Institutional Review Board-approved
      database of all patients presenting to our institution with aSAH from 1991 to
      2016 was analyzed. Cerebral angiography identified the source of hemorrhage.
      Patients with nonaneurysmal etiologies were excluded. RESULTS: Complete data were
      available for 1306/1562 patients (84%) with aSAH from 1991 to 2016. The average
      age was 53 yr and 72% of patients were female. The average size of ruptured
      aneurysms over 25 yr was 8.0 mm. The average size of ruptured aneurysms decreased
      steadily with each 5-yr interval from 10.1 mm (1991-1996) to 6.6 mm (2012-2016; P
      < .001). Overall, very small aneurysms (<5 mm) were responsible for aSAH in 41%
      of patients. The percentage of very small ruptured aneurysms rose from 29% during
      the initial 5-yr period (1991-1996) to 50% in the most recent period. Likewise,
      the percentage of ruptured aneurysms that were 5 to 9 mm rose from 26% to 34% (P
      < .001). In the past 5 yr, aneurysms <10 mm accounted for 84% of aSAH. Vessel of
      origin (P = .097) and aneurysm location (P = .322) did not vary with time.
      CONCLUSION: Ruptured small and very small aneurysms represent a majority and
      increasing share of aSAH. Identification and prophylactic treatment of these
      aneurysms remains an important clinical role for cerebrovascular neurosurgery.

PMID- 29029313
TI  - Subjective-Objective Sleep Discrepancy Is Associated With Alterations in Regional
      Glucose Metabolism in Patients With Insomnia and Good Sleeper Controls.
AB  - Objectives: Sleep discrepancies are common in primary insomnia (PI) and include
      reports of longer sleep onset latency (SOL) than measured by polysomnography
      (PSG) or "negative SOL discrepancy." We hypothesized that negative SOL
      discrepancy in PI would be associated with higher relative glucose metabolism
      during nonrapid eye movement (NREM) sleep in brain networks involved in conscious
      awareness, including the salience, left executive control, and default mode
      networks. Methods: PI (n = 32) and good sleeper controls (GS; n = 30) completed
      [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans during NREM
      sleep, and relative regional cerebral metabolic rate for glucose (rCMRglc) was
      measured. Sleep discrepancy was calculated by subtracting PSG-measured SOL on the
      PET night from corresponding self-report values the following morning. We tested
      for interactions between group (PI vs. GS) and SOL discrepancy for rCMRglc during
      NREM sleep using both a region of interest mask and exploratory whole-brain
      analyses. Results: Significant group by SOL discrepancy interactions for rCMRglc
      were observed in several brain regions (pcorrected < .05 for all clusters). In
      the PI group, more negative SOL discrepancy (self-reported > PSG-measured SOL)
      was associated with significantly higher relative rCMRglc in the right anterior
      insula and middle/posterior cingulate during NREM sleep. In GS, more positive SOL
      discrepancy (self-reported < PSG-measured SOL) was associated with significantly
      higher relative rCMRglc in the right anterior insula, left anterior cingulate
      cortex, and middle/posterior cingulate cortex. Conclusions: Although preliminary,
      these findings suggest regions of the brain previously shown to be involved in
      conscious awareness, and the perception of PSG-defined states may also be
      involved in the phenomena of SOL discrepancy.

PMID- 29029316
TI  - The Need for, and the Role of the Toxicological Chemist in the Design of Safer
      Chemicals.
AB  - During the past several decades, there has been an ever increasing emphasis for
      designers of new commercial (nonpharmaceutical) chemicals to include
      considerations of the potential impacts a planned chemical may have on human
      health and the environment as part of the design of the chemical, and to design
      chemicals such that they possess the desired use efficacy while minimizing
      threats to human health and the environment. Achievement of this goal would be
      facilitated by the availability of individuals specifically and formally trained
      to design such chemicals. Medicinal chemists are specifically trained to design
      and develop safe and clinically efficacious pharmaceutical substances. No such
      formally trained science hybrid exists for the design of safer commercial
      (nonpharmaceutical) chemicals. This article describes the need for and role of
      the "toxicological chemist," an individual who is formally trained in synthetic
      organic chemistry, biochemistry, physiology, toxicology, environmental science,
      and in the relationships between structure and commercial use efficacy, structure
      and toxicity, structure and environmental fate and effects, and global hazard,
      and trained to integrate this knowledge to design safer commercially efficacious
      chemicals. Using examples, this article illustrates the role of the toxicological
      chemist in designing commercially efficacious, safer chemical candidates.

PMID- 29029315
TI  - From the Cover: 7,8-Dihydroxyflavone Rescues Lead-Induced Impairment of Vesicular
      Release: A Novel Therapeutic Approach for Lead Intoxicated Children.
AB  - Childhood lead (Pb2+) intoxication is a public health problem of global
      proportion. Lead exposure during development produces multiple effects on the
      central nervous system including impaired synapse formation, altered synaptic
      plasticity, and learning deficits. In primary hippocampal neurons in culture and
      hippocampal slices, Pb2+ exposure inhibits vesicular release and reduces the
      number of fast-releasing sites, an effect associated with Pb2+ inhibition of NMDA
      receptor-mediated trans-synaptic Brain-Derived Neurotrophic Factor (BDNF)
      signaling. The objective of this study was to determine if activation of TrkB,
      the cognate receptor for BDNF, would rescue Pb2+-induced impairments of vesicular
      release. Rats were chronically exposed to Pb2+ prenatally and postnatally until
      50 days of age. This chronic Pb2+ exposure paradigm enhanced paired-pulse
      facilitation of synaptic potentials in Schaffer collateral-CA1 synapses in the
      hippocampus, a phenomenon indicative of reduced vesicular release probability.
      Decreased vesicular release probability was confirmed by both mean-variance
      analysis and direct 2-photon imaging of vesicular release from hippocampal slices
      of rats exposed to Pb2+in vivo. We also found a Pb2+-induced impairment of
      calcium influx in Schaffer collateral-CA1 synaptic terminals. Intraperitoneal
      injections of Pb2+ rats with the TrkB receptor agonist 7,8-dihydroxyflavone (5
      mg/kg) for 14-15 days starting at postnatal day 35, reversed all Pb2+-induced
      impairments of presynaptic transmitter release at Schaffer collateral-CA1
      synapses. This study demonstrates for the first time that in vivo pharmacological
      activation of TrkB receptors by small molecules such as 7,8-dihydroxyflavone can
      reverse long-term effects of chronic Pb2+ exposure on presynaptic terminals,
      pointing to TrkB receptor activation as a promising therapeutic intervention in
      Pb2+-intoxicated children.

PMID- 29029317
TI  - The Critical Role of Supply Chains in Preventing Human Immunodeficiency Virus
      Drug Resistance in Low- and Middle-Income Settings.
AB  - The functioning of the supply chain may be a driving factor behind the
      development of human immunodeficiency virus (HIV) drug resistance (HIVDR) in many
      low- and middle-income countries (LMICs). Additionally, the effectiveness of
      supply chains will likely impact the scale-up of both viral-load monitoring and
      HIVDR testing. This article describes the complexities of global supply chains
      relevant for LMICs and presents early data on stock-outs and drug substitutions
      in several countries supported by the US President's Emergency Plan for AIDS
      Relief. Supply chain systems will need to be strengthened to minimize
      interruptions as new antiretroviral therapy regimens are introduced and to
      facilitate adoption of new laboratory technologies.

PMID- 29029318
TI  - Eliminating the Controlled Napping Policy at CSX Is a Blow to Public Safety.

PMID- 29029319
TI  - New Records of Phlebotomine Sand Flies (Diptera: Psychodidae) From the State of
      Alagoas, Northeast of Brazil.
AB  - Phlebotomine sand flies are small insects of great medical importance. This study
      presents new records of phlebotomine sand flies, which augment the list of
      species, recorded in the state of Alagoas, Brazil. Sand flies were collected
      using CDC miniature light traps. Collections were made between November 2008 and
      April 2016, in 47 municipalities within the state of Alagoas. Twenty-seven
      thousand two-hundred forty-four sand flies were collected, representing 18
      species in seven genera. Lutzomyia longipalpis was the predominant species (85.4%
      of total), and it was recorded in all biomes. Three species (Evandromyia evandroi
      (Costa Lima and Antunes 1936), Evandromyia tupynambai (Mangabeira 1942), and
      Pressatia choti (Floch and Abonnenc 1941)) were collected in coastal and Atlantic
      forest biomes; five species (Lutzomyia villelai (Mangabeira 1942), Micropygomyia
      oswaldoi (Mangabeira 1942), Nyssomyia umbratilis (Ward and Frahia 1977),
      Nyssomyia intermedia (Lutz and Neiva 1912), and Nyssomyia whitmani (Antunes and
      Coutinho 1939)) were collected in Atlantic forest and Caatinga biomes. The
      species Evandromyia corumbaensis (Galati, Nunes, Oshiro and Rego 1989) and
      Psathyromyia naftalekatzi (Falcao, Andrade-Filho, Almeida and Brandao-Filho 2000)
      were found only in the coastal zones. This work provides an updated list of the
      phlebotomine sand flies of Alagoas, with some notes on their taxonomy, ecology,
      distribution, and epidemiological relevance.

PMID- 29029320
TI  - Insecticidal Mechanism of Wintergreen Oil Against the Health Pest Paederus
      fuscipes (Coleoptera: Staphylinidae).
AB  - Paederus fuscipes, a health pest, causes dermatitis linearis in humans.
      Wintergreen oil exhibits optimal insecticidal activity against P. fuscipes.
      However, the insecticidal mechanism remains unclear not only in P. fuscipes but
      also in other pests. In this study, we explored the insecticidal mechanism of
      wintergreen oil in terms of its effect on the activity of acetylcholinesterase
      (AChE) enzyme and detoxifying enzymes (carboxylesterase, glutathione-S
      transferase, and mixed function oxidase); such effect was studied by fumigation
      both in vivo and in vitro in P. fuscipes male and female adults. In the in vivo
      and in vitro experiments on male and female adults, wintergreen oil did not
      significantly affect the activities of the three detoxifying enzymes. Hence, the
      mode of action of wintergreen oil may be unrelated to the three detoxifying
      enzymes. Wintergreen oil significantly inhibited AChE activity. When wintergreen
      oil was tested at different times in vivo, the highest inhibition rates were
      41.99% (male) and 40.91% (female). When different doses of wintergreen oil were
      used for in vivo treatment, the highest inhibition rates were 33.78% (male) and
      43.33% (female). When wintergreen oil was tested in vitro, the highest inhibition
      rates were 31.06% (male) and 35.57% (female). In vitro with chlorpyrifos as a
      positive control, the AChE activity of 3-MUl wintergreen oil treatment was
      significantly lower than that of 10 mg/liter chlorpyrifos in both P. fuscipes
      male and female adults. The results demonstrated that AChE is a potential key
      factor, maybe a target enzyme, in the mechanism of wintergreen oil against P.
      fuscipes.

PMID- 29029321
TI  - Rapid Novel Facile Biosynthesized Silver Nanoparticles From Bacterial Release
      Induce Biogenicity and Concentration Dependent In Vivo Cytotoxicity With
      Embryonic Zebrafish-A Mechanistic Insight.
AB  - In this study, rapid one step facile synthesis of silver nanoparticles (AgNPs)
      was done using culture supernatant of two Gram positive (B. thuringiensis and S.
      aureus) and Gram negative (E. coli and Salmonella typhimurium [STAgNP]) bacterial
      strains and were termed as "Bacillus thuringiensis," "Staphylococcus aureus,"
      "Escherichia coli," and "STAgNP," respectively. Synthesized AgNPs were well
      characterized with the help of different standard techniques like FESEM, DLS, UV
      Vis spectroscopy, and Fourier transform infrared. Mechanism of AgNPs synthesis
      was elucidated using in silico approach. In vivo cytotoxicity of synthesized
      AgNPs was assessed in embryonic Zebrafish model with the help of uptake,
      oxidative stress, and apoptosis induction experimental assays, and the mechanism
      was investigated through in silico approach at the molecular level. The result
      showed successful biosynthesis of 20-40 nm sized AgNPs stable with zeta potential
      of - 45 to - 35 mV having standard silver nanoparticles SPR peaks due to the
      interaction of reduced silver particles with amino acid residues of bapA proteins
      of the bacterial supernatant. In vivo cytotoxicity with embryonic Zebrafish was
      found to be dependent on biogenicity and concentration of biosynthesized AgNPs as
      consequence of oxidative stress induction and apoptosis due to the influential
      regulation of sod1 and tp53 genes clarified by pathway analysis with reference to
      experimental and computational results. The study suggested that cytotoxicity of
      biologically synthesized silver nanoparticles from bacteria depends on strain
      specificity with significant difference in use of Gram positive and Gram negative
      bacterial strains.

PMID- 29029322
TI  - A Dynamic Mathematical Model of Bile Acid Clearance in HepaRG Cells.
AB  - A dynamic model based on ordinary differential equations that describes uptake,
      basolateral and canalicular export of taurocholic acid (TCA) in human HepaRG
      cells is presented. The highly reproducible inter-assay experimental data were
      used to reliably estimate model parameters. Primary human hepatocytes were
      similarly evaluated to establish a mathematical model, but with notably higher
      inter-assay differences in TCA clearance and bile canaliculi dynamics. By use of
      the HepaRG cell line, the simultaneous TCA clearance associated to basolateral
      uptake, canalicular and sinusoidal efflux, was predicted. The mathematical model
      accurately reproduced the dose-dependent inhibition of TCA clearance in the
      presence and absence of the prototypical cholestatic drugs cyclosporine A (CsA)
      and chlorpromazine. Rapid inhibition of TCA clearance and recovery were found to
      be major characteristics of CsA. Conversely, the action of chlorpromazine was
      described by slow onset of inhibition relative to inhibition of TCA clearance by
      CsA. The established mathematical model, validated by the use of these 2
      prototypical cholestatic drugs and the integration of bile canalicular dynamics,
      provides an important development for the further study of human hepatobiliary
      function, through simultaneous temporal and vectorial membrane transport of bile
      acids in drug-induced cholestasis.

PMID- 29029323
TI  - Editor's Highlight: lncRNAL20992 Regulates Apoptotic Proteins to Promote Lead
      Induced Neuronal Apoptosis.
AB  - Lead is a heavy metal pollutant that is widely present in the environment and can
      seriously harm human health, especially the nervous system. Long noncoding RNAs
      (lncRNAs) play important roles in many physiological and pathological processes;
      however, there remains a lack of in-depth studies on the molecular mechanisms
      associated with lead neurotoxicity. Here, our results showed that lead exposure
      inhibited cell proliferation and promoted cell apoptosis. We observed that
      lncRNAL20992 was significantly upregulated in a lead-induced neuronal-injury cell
      model according to quantitative reverse transcription polymerase chain reaction.
      Silencing lncRNAL20992 revealed its significant functions involved in promoting
      cell apoptosis and inhibiting cell proliferation according to cell-counting kit
      8, EdU assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling, and
      western blot. To elucidate the molecular mechanisms of lncRNAL20992, we used RNA
      pulldown mass spectrometry combined with bioinformatics analysis to discover 4
      proteins (AIFM1, HSP7C, GRP78, and LMNA) that interacted with lncRNAL20992.
      Western blot analysis indicated that lncRNAL20992 involved in lead-induced
      neuronal injury was mediated by the 4 proteins. Our study constitutes the first
      investigation of the functions and related mechanisms of lncRNAL20992 and offered
      valuable insight into understanding the roles of lncRNA in lead-induced
      neurotoxicity.

PMID- 29029325
TI  - Guidelines for the Use of Electrophysiological Monitoring for Surgery of the
      Human Spinal Column and Spinal Cord.

PMID- 29029326
TI  - Letter: Electric Beats Open New Frontiers for Deep Brain Stimulation.

PMID- 29029324
TI  - Cadmium Exposure Impairs Cognition and Olfactory Memory in Male C57BL/6 Mice.
AB  - Cadmium (Cd) is a heavy metal of high interest to the superfund initiative.
      Recent epidemiology studies have suggested a possible association between Cd
      exposure and cognitive as well as olfactory impairments in humans. However,
      studies in animal models are needed to establish a direct causal relationship
      between Cd exposure and impairments in cognition and olfaction. This study aims
      to investigate the toxic effect of Cd on cognition and olfactory function in
      mice. One group of 8-week-old C57BL/6 male mice was exposed to 3 mg/l Cd (in the
      form of CdCl2) through drinking water for 20 weeks for behavior tests and final
      blood Cd concentration analysis. The behavior tests were conducted before,
      during, and after Cd exposure to analyze the effects of Cd on cognition and
      olfactory function. Upon completion of behavior tests, blood was collected to
      measure final blood Cd concentration. Two additional groups of mice were
      similarly exposed to Cd for 5 or 13 weeks for peak blood Cd concentration
      measurement. The peak blood Cd concentration was 2.125-2.25 MUg/l whereas the
      final blood Cd concentration was 0.18 MUg/l. At this exposure level, Cd impaired
      hippocampus-dependent learning and memory in novel object location test, T-maze
      test, and contextual fear memory test. It also caused deficits in short-term
      olfactory memory and odor-cued olfactory learning and memory. Results in this
      study demonstrate a direct relationship between Cd exposure and cognitive as well
      as olfactory impairments in an animal model.

PMID- 29029327
TI  - The Exonization and Functionalization of an Alu-J Element in the Protein Coding
      Region of Glycoprotein Hormone Alpha Gene Represent a Novel Mechanism to the
      Evolution of Hemochorial Placentation in Primates.
AB  - Alu elements contribute considerably to gene regulation and genome evolution in
      primates. The generation of new exons from Alu elements has been found in various
      human genes, and the regulatory function of the Alu exon has been investigated in
      many studies. However, the functionalization of Alu elements in protein coding
      regions remains unknown. Here, we reported that an Alu-J element exonized in the
      glycoprotein hormone alpha (GPHA) gene and encoded an additional N-terminal
      peptide (Alu-J encoding peptide) of the mature GPHA peptide, leading to a
      splicing variant of Alu-GPHA in anthropoid primates ~35 Ma. Interestingly,
      adaptive evolution of the Alu-J exon occurred in the human and ape lineages
      during anthropoid evolution. The Alu-J encoding peptide is found to be a new
      biomarker in human early pregnancy and prolongs the serum half-life of human
      chorionic gonadotropin (HCG) circulation. Moreover, Alu-J encoding peptide
      enhances the bioactivity of HCG protein, both in vivo and in vitro. Our study
      reveals the first example of an Alu element functioning as the encoding peptide
      to increase the whole protein stability and provides insight into the potential
      multi-functionalization of the Alu exon in the protein coding regions.
      Furthermore, with the chorionic gonadotropin linking with hemochorial
      placentation, the exonization and functionalization of the Alu-J exon in GPHA
      gene represent a novel mechanism to the evolution of hemochorial placentation in
      primates.

PMID- 29029328
TI  - Predicting deaths in a resource-limited neonatal intensive care unit in Nepal.
AB  - Background: This study aimed to determine whether the Neonatal Acute Physiology
      (SNAP) scoring system (SNAP II) and with perinatal extension (SNAP II PE) can be
      used to predict neonatal deaths in a resource-limited neonatal intensive care
      unit in Nepal. Methods: A prospective observational study was conducted in a
      neonatal intensive care unit (NICU) of Kanti Children's Hospital in Kathmandu,
      Nepal. Data required for the SNAP II and SNAP II PE scores were collected. The
      relationships between the SNAP II and SNAP II PE scores and neonatal mortality
      were analyzed. Results: There were 135 neonates admitted during the 6 month study
      period, of whom 126 met the inclusion criteria. Of these 126 neonates, 29 (23.0%)
      died. Mortality was 83% (5/6) when SNAP II was >40, and 66.7% (6/9) when SNAP II
      PE was >50. A SNAP II score of >=12 had a sensitivity of 75.9%, and specificity
      of 73.2% for predicting mortality, and a SNAP II PE score of >=14 had a
      sensitivity of 82.8% and specificity of 67.0% for it. Conclusions: SNAP II and
      SNAP II PE scoring of neonates can be used to predict prognosis of neonates in
      resource-limited NICUs in Nepal.

PMID- 29029329
TI  - A New Anthropophilic Species of Simulium (Trichodagmia) (Diptera: Simuliidae)
      From Amazonia: Morphology, Chromosomes, and DNA Sequences.
AB  - The black fly Simulium (Trichodagmia) hirtipupa Lutz (Diptera: Simuliidae) is
      widely distributed in southern Brazil, with one report from Amapa state in the
      northern region of Brazilian Amazonia. Morphological comparison of northern and
      southern populations revealed differences in all life stages, corroborated by
      chromosomal and molecular analyses, and indicated that the population previously
      identified as S. hirtipupa from Amapa state represents an undescribed species.
      This new species is described based on all life stages above the egg, and its
      chromosomal and molecular divergence from S. hirtipupa is highlighted. Simulium
      criniferum n. sp. can be diagnosed by the deeply concave male ventral plate with
      a prominent median projection bearing a ventral keel; female anal lobe in lateral
      view with a broadly rounded, distal membranous area about as long as wide; pupa
      with a boot-shaped cocoon bearing a minutely bubbled surface, cephalic plate and
      thorax with abundant hair-like tubercles, and gill of 12 translucent filaments
      with darkly sclerotized, acuminate tips; and larva with the body cuticle bearing
      spiniform setae, abdomen truncated posteriorly, and gill histoblast in situ with
      the filament tips directed ventrally. Chromosomally, the new species has five
      unique fixed inversions and uniquely shares three additional fixed inversions
      with its nearest relative, S. hirtipupa. Partial COI sequences indicate a genetic
      distance of ~9% between the new species and S. hirtipupa. Females of the new
      species are anthropophilic.

PMID- 29029331
TI  - The clinical utility of human leucocyte antigen B27 in axial spondyloarthritis.
AB  - The association between HLA-B27 and AS was first established in the early 1970s.
      Since then, our understanding of this disease has changed, such that we now
      recognize AS to be the extreme of the clinical phenotype within a disease
      spectrum known as axial SpA (axSpA). Recent advances in therapeutic options have
      driven the need for earlier diagnosis and many screening strategies have been
      proposed to facilitate this. In parallel, our understanding of axSpA genetics,
      and especially the contribution of HLA-B27, has expanded. In this article we will
      present and discuss the evidence supporting the use of HLA-B27 in clinical
      practice. We will briefly summarize the evolution of the concept of axSpA, the
      prevalence of HLA-B27 and axSpA and the potential role of HLA-B27 in the
      aetiopathogenesis of axSpA and focus on the utility of HLA-B27 in everyday
      clinical practice.

PMID- 29029330
TI  - The association between omega-3 fatty acid biomarkers and inflammatory arthritis
      in an anti-citrullinated protein antibody positive population.
AB  - Objectives: Higher circulating omega-3 fatty acids (n-3 FAs) are associated with
      a lower prevalence of anti-CCP antibodies and RF in subjects without RA. We
      examined whether, in anti-CCP+ subjects, n-3 FAs also play a role in development
      of inflammatory arthritis (IA). Methods: At Colorado-based health fairs from 2008
      to 2014, participants without a previous diagnosis of RA who were anti-CCP3+ (n =
      47) were recruited into a follow-up study; symptom assessments and joint
      examinations were conducted every 6 months for the determination of IA. We
      measured n-3 FAs as a percentage of total lipids in red blood cell membranes (n-3
      FA%) at each visit. Results: We detected IA in 10 anti-CCP3+ subjects (21%) at
      the baseline visit. Increased total n-3 FA% in red blood cell membranes [odds
      ratio (OR) = 0.09, 95% CI: 0.01, 0.76], specifically docosapentaenoic acid (OR =
      0.16, 95% CI: 0.03, 0.83) and docosahexaenoic acid (OR = 0.23, 95% CI: 0.06,
      0.86), was associated with a lower odds of IA at the baseline visit, adjusting
      for n-3 FA supplement use, current smoking, RF+, elevated CRP+ and shared
      epitope. We followed 35 of the anti-CCP3+ subjects who were IA negative at
      baseline and detected 14 incident IA cases over an average of 2.56 years of
      follow-up. In a time-varying survival analysis, increasing docosapentaenoic acid
      significantly decreased risk of incident IA (hazard ratio = 0.52, 95% CI: 0.27,
      0.98), adjusting for age at baseline, n-3 FA supplement use, RF+, CRP+ and shared
      epitope. Conclusion: n-3 FAs may potentially lower the risk of transition from
      anti-CCP positivity to IA, an observation that warrants further investigation.

PMID- 29029332
TI  - Identification of a Novel Subset of Myeloid-Derived Suppressor Cells During
      Chronic Staphylococcal Infection That Resembles Immature Eosinophils.
AB  - We have previously reported that myeloid-derived suppressor cells (MDSC), which
      are a heterogeneous population of immunosuppressive immature myeloid cells,
      expanded during chronic Staphylococcus aureus infection and promoted bacterial
      persistence by inhibiting effector T cells. Two major MDSC subsets, including
      monocytic MDSC and granulocytic MDSC, have been described to date. Here, we
      identified a new subset of MDSC (Eo-MDSC) in S. aureus-infected mice that
      phenotypically resembles eosinophils. Eo-MDSC exhibit eosinophilic cytoplasmic
      granules and express CD11b, the eosinophil marker Syglec-F, variable levels of
      CCR3, and low levels of interleukin-5Ralpha. Furthermore, Eo-MDSC accumulated at
      the site of infection and exerted a potent immunosuppressive effect on T-cell
      responses that was mediated by nitric oxide-dependent depletion of l-arginine.
      Increases in the number of Eo-MDSC by adoptive transfer caused a significant
      exacerbation of infection in S. aureus-infected mice. This study sheds new light
      on the heterogeneity and complexity of MDSC during chronic infection.

PMID- 29029334
TI  - Effect of long-term hydroxychloroquine on vascular events in patients with
      systemic lupus erythematosus: a database prospective cohort study.
AB  - Objectives: The incidence of thromboembolism in patients with SLE is higher than
      that in the general population. HCQ, widely used to treat lupus, may have
      vascular protective effects. The aim of this study was to determine whether long
      term HCQ exposure is associated with decreased thromboembolism risk in SLE.
      Methods: We designed a prospective cohort study within an SLE population based on
      the National Health Insurance Research Database in Taiwan. We divided
      participants into HCQ and control groups according to HCQ prescription during the
      first year. These groups were defined by medication possession ratio (MPR) ?80%
      and MPR = 0%, respectively. Patients with an MPR between 0 and 80% were excluded.
      The primary outcome was a composite vascular event, including acute coronary
      syndrome, ischaemic stroke, pulmonary embolism, deep vein thrombosis and
      peripheral arterial disease 1 year after inclusion. We excluded patients from the
      cohort if they had outcomes within the first year. Results: A total of 8397
      patients were eligible for analysis. After propensity-score matching, we included
      1946 patients in each group. During a mean follow-up of 7.4 years, the number of
      events was 139 in the HCQ group (7.1%) and 149 in the control group (7.7%). The
      risk of vascular events in the HCQ group was similar to that in the control group
      (hazard ratio = 0.91; 95% CI: 0.72, 1.15). Further subgroup analyses confirmed no
      statistically significant differences between the groups. Conclusion: Long-term
      HCQ appears to have no vascular protective effect in patients with SLE.

PMID- 29029335
TI  - Cortical Reorganization in Dual Innervation by Single Peripheral Nerve.
AB  - BACKGROUND: Functional recovery after peripheral nerve injury and repair is
      related with cortical reorganization. However, the mechanism of innervating dual
      targets by 1 donor nerve is largely unknown. OBJECTIVE: To investigate the
      cortical reorganization when the phrenic nerve simultaneously innervates the
      diaphragm and biceps. METHODS: Total brachial plexus (C5-T1) injury rats were
      repaired by phrenic nerve-musculocutaneous nerve transfer with end-to-side (n =
      15) or end-to-end (n = 15) neurorrhaphy. Brachial plexus avulsion (n = 5) and
      sham surgery (n = 5) rats were included for control. Behavioral observation,
      electromyography, and histologic studies were used for confirming peripheral
      nerve reinnervation. Cortical representations of the diaphragm and reinnervated
      biceps were studied by intracortical microstimulation techniques before and at
      months 0.5, 3, 5, 7, and 10 after surgery. RESULTS: At month 0.5 after complete
      brachial plexus injury, the motor representation of the injured forelimb
      disappeared. The diaphragm representation was preserved in the "end-to-side"
      group but absent in the "end-to-end" group. Rhythmic contraction of biceps
      appeared in "end-to-end" and "end-to-side" groups, and the biceps representation
      reappeared in the original biceps and diaphragm areas at months 3 and 5. At month
      10, it was completely located in the original biceps area in the "end-to-end"
      group. Part of the biceps representation remained in the original diaphragm area
      in the "end-to-side" group. Destroying the contralateral motor cortex did not
      eliminate respiration-related contraction of biceps. CONCLUSION: The brain tends
      to resume biceps representation from the original diaphragm area to the original
      biceps area following phrenic nerve transfer. The original diaphragm area partly
      preserves reinnervated biceps representation after end-to-side transfer.

PMID- 29029333
TI  - More than Counting: An Intraindividual Variability Approach to Categorical
      Repeated Measures.
AB  - Objectives: Age-related differences in daily experiences are often described
      using summaries of categorical repeated measures, including typologies of
      stressors, activities, social partners, and coping strategies. This paper
      illustrates how an intraindividual variability (IIV) framework can be used to
      extract additional meaning from categorical IIV data. Method: Using 8-occasion
      categorical data on daily stressors from the National Study of Daily Experiences
      (N = 1,499, MAge = 46.74, SDAge= 12.91), we derive and compute six IIV metrics
      that invoke numeric and nominal measurement of the central tendency, dispersion,
      and asymmetry of individuals' stressor experiences and examine how these metrics,
      relative dominance, diversity, log-skew and mode, spread, order, are related to
      age and interindividual differences in negative affect. Results: Results
      demonstrate the utility of the numeric and nominal categorical IIV metrics, with
      theoretically meaningful age gradients in the three numeric IIV stressor metrics
      and five of six IIV metrics mapping differences in negative affect. Discussion:
      Findings highlight how the unique constructs measured by these six metrics of
      categorical IIV may be used to examine dynamic process, study interindividual and
      age-related differences, and expand the variety of developmental research
      questions that may be answered using categorical repeated measures data.

PMID- 29029336
TI  - Editor's Highlight: Differential Effects of Exposure to Single Versus a Mixture
      of Endocrine-Disrupting Chemicals on Steroidogenesis Pathway in Mouse Testes.
AB  - Endocrine-disrupting chemicals (EDCs) generate reproductive dysfunctions
      affecting the biosynthesis of steroid hormones and genes of the steroidogenic
      pathway. EDCs effects are mainly reported as a result of exposure to single
      compounds. However, humans are environmentally exposed to a mixture of EDCs.
      Herein, we assess chronic exposure to single alkylphenols and phthalates versus a
      mixture in mouse testes histology and steroidogenesis. Pregnant mice were exposed
      through drinking water to: 0.3 mg/kg-body weight (BW)/d of each phthalate (bis (2
      ethylhexyl) phthalate, dibutyl phthalate, benzyl butyl phthalate), 0.05 mg/kg
      BW/d of each alkylphenol (4-nonylphenol, 4-tert-octylphenol), or their mixture,
      covering from 0.5 postcoital day to weaning, continuing in the male offspring
      each exposure until adulthood (60-days old). Body and relative testis weight were
      increased in mixture-exposed mice along with histological alterations.
      Intratesticular testosterone (T) changed only in mice exposed to DBP, whereas
      estradiol (E2) levels were altered in all groups (except benzyl butyl phthalate).
      mRNA levels of genes encoding hormones of the steroid pathway (Cyp11a1, Hsd3b1,
      Cyp17a1, and Cyp19a1), cholesterol transporters (Star), and transcriptional
      factors (Sp1) showed that mice exposed to single or mixed compounds had
      alterations in at least 2 transcripts. However, none of the different types of
      exposure induced changes in all transcripts. In addition, changes at the mRNA or
      protein levels with single compounds were not always the same as those with a
      mixture. In conclusion, the effects of a chronic exposure to a mixture of EDCs on
      the expression of genes and proteins of the steroidogenic pathway and hormonal
      status were different from those exposed to single EDC.

PMID- 29029337
TI  - Protective Effect of Indoor Residual Spraying of Insecticide on Preterm Birth
      Among Pregnant Women With HIV Infection in Uganda: A Secondary Data Analysis.
AB  - Background: Recent evidence demonstrated improved birth outcomes among human
      immunodeficiency virus (HIV)-uninfected pregnant women protected by indoor
      residual spraying of insecticide (IRS). Evidence regarding its impact on HIV
      infected pregnant women is lacking. Methods: Data were pooled from 2 studies
      conducted before and after an IRS campaign in Tororo, Uganda, among HIV-infected
      pregnant women who received bed nets, daily trimethoprim-sulfamethoxazole, and
      combination antiretroviral therapy at enrollment. Exposure was the proportion of
      pregnancy protected by IRS. Adverse birth outcomes included preterm birth, low
      birth weight, and fetal or neonatal death. Multivariate Poisson regression with
      robust standard errors was used to estimate risk ratios. Results: Of 565 women in
      our analysis, 380 (67%), 88 (16%), and 97 (17%) women were protected by IRS for
      0%, >0% to 90%, and >90% of their pregnancy, respectively. Any IRS protection
      significantly reduced malaria incidence during pregnancy and placental malaria
      risk. Compared with no IRS protection, >90% IRS protection reduced preterm birth
      risk (risk ratio, 0.35; 95% confidence interval, .15-.84), with nonsignificant
      decreases in the risk of low birth weight (0.68; .29-1.57) and fetal or neonatal
      death (0.24; .04-1.52). Discussion: Our exploratory analyses support the
      hypothesis that IRS may significantly reduce malaria and preterm birth risk among
      pregnant women with HIV receiving bed nets, daily trimethoprim-sulfamethoxazole,
      and combination antiretroviral therapy.

PMID- 29029338
TI  - To Include or Not to Include: The Impact of Gene Filtering on Species Tree
      Estimation Methods.
AB  - With the increasing availability of whole genome data, many species trees are
      being constructed from hundreds to thousands of loci. Although concatenation
      analysis using maximum likelihood is a standard approach for estimating species
      trees, it does not account for gene tree heterogeneity, which can occur due to
      many biological processes, such as incomplete lineage sorting. Coalescent species
      tree estimation methods, many of which are statistically consistent in the
      presence of incomplete lineage sorting, include Bayesian methods that coestimate
      the gene trees and the species tree, summary methods that compute the species
      tree by combining estimated gene trees, and site-based methods that infer the
      species tree from site patterns in the alignments of different loci. Due to
      concerns that poor quality loci will reduce the accuracy of estimated species
      trees, many recent phylogenomic studies have removed or filtered genes on the
      basis of phylogenetic signal and/or missing data prior to inferring species
      trees; little is known about the performance of species tree estimation methods
      when gene filtering is performed. We examine how incomplete lineage sorting,
      phylogenetic signal of individual loci, and missing data affect the absolute and
      the relative accuracy of species tree estimation methods and show how these
      properties affect methods' responses to gene filtering strategies. In particular,
      summary methods (ASTRAL-II, ASTRID, and MP-EST), a site-based coalescent method
      (SVDquartets within PAUP*), and an unpartitioned concatenation analysis using
      maximum likelihood (RAxML) were evaluated on a heterogeneous collection of
      simulated multilocus data sets, and the following trends were observed. Filtering
      genes based on gene tree estimation error improved the accuracy of the summary
      methods when levels of incomplete lineage sorting were low to moderate but did
      not benefit the summary methods under higher levels of incomplete lineage
      sorting, unless gene tree estimation error was also extremely high (a model
      condition with few replicates). Neither SVDquartets nor concatenation analysis
      using RAxML benefited from filtering genes on the basis of gene tree estimation
      error. Finally, filtering genes based on missing data was either neutral (i.e.,
      did not impact accuracy) or else reduced the accuracy of all five methods. By
      providing insight into the consequences of gene filtering, we offer
      recommendations for estimating species tree in the presence of incomplete lineage
      sorting and reconcile seemingly conflicting observations made in prior studies
      regarding the impact of gene filtering.

PMID- 29029339
TI  - Targeted Enrichment of Large Gene Families for Phylogenetic Inference: Phylogeny
      and Molecular Evolution of Photosynthesis Genes in the Portullugo Clade
      (Caryophyllales).
AB  - Hybrid enrichment is an increasingly popular approach for obtaining hundreds of
      loci for phylogenetic analysis across many taxa quickly and cheaply. The genes
      targeted for sequencing are typically single-copy loci, which facilitate a more
      straightforward sequence assembly and homology assignment process. However, this
      approach limits the inclusion of most genes of functional interest, which often
      belong to multi-gene families. Here, we demonstrate the feasibility of including
      large gene families in hybrid enrichment protocols for phylogeny reconstruction
      and subsequent analyses of molecular evolution, using a new set of bait sequences
      designed for the "portullugo" (Caryophyllales), a moderately sized lineage of
      flowering plants (~ 2200 species) that includes the cacti and harbors many
      evolutionary transitions to C$_{?mathrm{4}}$ and CAM photosynthesis. Including
      multi-gene families allowed us to simultaneously infer a robust phylogeny and
      construct a dense sampling of sequences for a major enzyme of C$_{?mathrm{4}}$
      and CAM photosynthesis, which revealed the accumulation of adaptive amino acid
      substitutions associated with C$_{?mathrm{4}}$ and CAM origins in particular
      paralogs. Our final set of matrices for phylogenetic analyses included 75-218
      loci across 74 taxa, with ~ 50% matrix completeness across data sets.
      Phylogenetic resolution was greatly improved across the tree, at both shallow and
      deep levels. Concatenation and coalescent-based approaches both resolve the
      sister lineage of the cacti with strong support: Anacampserotaceae $+$
      Portulacaceae, two lineages of mostly diminutive succulent herbs of warm, arid
      regions. In spite of this congruence, BUCKy concordance analyses demonstrated
      strong and conflicting signals across gene trees. Our results add to the growing
      number of examples illustrating the complexity of phylogenetic signals in genomic
      scale data.

PMID- 29029340
TI  - Circadian Phase and Phase Angle Disorders in Primary Insomnia.
AB  - Objectives: We aimed to identify the prevalence of circadian phase and phase
      angle abnormalities in patients with insomnia. Methods: We conducted a cross
      sectional, multicenter study at three sleep laboratories in the United States and
      Australia. Patients with insomnia and healthy control participants completed a
      sleep log for 7 days. Circadian phase was assessed from salivary dim light
      melatonin onset (DLMO) time during a 12-hour laboratory visit. Results: Seventy
      nine patients meeting the Research Diagnostic Criteria for Primary,
      Psychophysiological, Paradoxical, and/or Idiopathic Childhood Insomnia (46
      females, 35.5 +/- 12.3 years [M +/- SD]) and 21 controls (14 females, 34.4 +/-
      11.8 years). As compared to controls, patients with insomnia tried to initiate
      sleep on average at the same clock time (24:17 +/- 1:17 hours vs. 24:13 +/- 1:30
      hours, respectively; p = .84) but had a later average DLMO times (20:56 +/- 1:55
      hours, 18:17-01:21 vs. 22:02 +/- 2:02 hours, 17:11-04:52, respectively; p = .04).
      Consequently, patients with insomnia slept at an earlier circadian phase than
      controls (phase angle, bedtime-DLMO 2:13 hours (+/- 1:43) vs. 3:10 hours (+/-
      1:08), respectively; p = .008), of whom 10% tried to sleep at or before DLMO
      (compared to 0 controls), and 22% tried to sleep before or within 1 hour after
      DLMO (compared to 6% of controls). Conclusions: A substantial proportion (10%
      22%) of patients with insomnia initiate sleep at too early a circadian phase,
      implicating a circadian etiology for their insomnia. Outpatient circadian phase
      assessments should be considered to improve differential diagnoses in insomnia
      and to inform the development of appropriately timed circadian-based treatments.

PMID- 29029341
TI  - An increased concentration of receptor activator of nuclear factor kappa-B ligand
      pre-dates the onset of rheumatoid arthritis.
AB  - Objectives: RANK ligand (RANKL) is involved in destruction and osteoporosis in
      RA. In this study, the relationships between RANKL and ACPA, anti-carbamylated
      protein antibodies (anti-CarP), cytokines and chemokines were analysed in
      individuals before the onset of RA symptoms, and their associations with
      radiological findings at disease onset were assessed. Methods: This was a case
      control study performed within the Medical Biobank of Northern Sweden that
      included 470 pre-symptomatic individuals [334 women and 136 men; mean (s.d.) age
      52.3 (9.4) years] using blood samples donated before symptom onset (pre-dating
      time; 5.0 years) and 96 controls (60 women and 36 men). Plasma was analysed for
      RANKL (BioVendor, Karasek, Brno, Czech Republic), anti-CCP2 antibodies
      (Eurodiagnostics, Malmo, Sweden), anti-CarP antibodies (in-house ELISA), ACPA
      specificities (ISAC-platform, Phadia AB, Uppsala, Sweden) and
      cytokines/chemokines (Meso Scale Discovery methods, Rockville, MD, USA).
      Radiographs of hands and feet were graded using the Larsen score. Results: The
      concentration of RANKL was higher in the pre-symptomatic individuals compared
      with controls; mean (s.e.m.): 0.50 (0.03) vs 0.22 (0.02) nmol/l (P < 0.001). The
      concentration increased gradually over time until symptom onset but appeared
      later than ACPA/RF/anti-CarP antibodies. Positivity for these antibodies yielded
      higher levels of RANKL compared with seronegativity (P < 0.001). RANKL
      concentrations were significantly associated with IL-6 and IL-10 concentrations.
      The combination of positivity for RANKL and anti-CarP antibodies resulted in a
      higher Larsen score at diagnosis beta = 6.18 (95% CI: 0.93, 11.43; P = 0.022).
      Conclusion: RANKL concentrations were increased several years before symptom
      onset for RA, particularly in ACPA/RF/anti-CarP-positive individuals, all
      detectable earlier than RANKL. Positivity for RANKL and anti-CarP antibodies
      yielded the highest Larsen score at disease onset.

PMID- 29029342
TI  - STRIDE: Species Tree Root Inference from Gene Duplication Events.
AB  - The correct interpretation of any phylogenetic tree is dependent on that tree
      being correctly rooted. We present STRIDE, a fast, effective, and outgroup-free
      method for identification of gene duplication events and species tree root
      inference in large-scale molecular phylogenetic analyses. STRIDE identifies sets
      of well-supported in-group gene duplication events from a set of unrooted gene
      trees, and analyses these events to infer a probability distribution over an
      unrooted species tree for the location of its root. We show that STRIDE correctly
      identifies the root of the species tree in multiple large-scale molecular
      phylogenetic data sets spanning a wide range of timescales and taxonomic groups.
      We demonstrate that the novel probability model implemented in STRIDE can
      accurately represent the ambiguity in species tree root assignment for data sets
      where information is limited. Furthermore, application of STRIDE to outgroup-free
      inference of the origin of the eukaryotic tree resulted in a root probability
      distribution that provides additional support for leading hypotheses for the
      origin of the eukaryotes.

PMID- 29029345
TI  - Evacuating People and Their Pets: Older Floridians' Need for and Proximity to Pet
      Friendly Shelters.
AB  - Objectives: Pets influence evacuation decisions, but little is known about pet
      friendly emergency shelters' availability or older adults' need for them. Our
      study addresses this issue, focusing on the most densely populated area of
      Florida (Miami-Dade)-the state with the oldest population and greatest hurricane
      susceptibility. Method: We use Geographic Information Systems (GIS)-based
      methodology to identify the shortest paths to pet-friendly shelters, based on
      distance and congested and uncongested travel times-taking into account the older
      population's spatial distribution. Logistic regression models using the 2013
      American Housing Survey's Disaster Planning Module examine anticipated shelter
      use as a function of pet ownership and requiring pet evacuation assistance.
      Results: Thirty-four percent of older adults in the Miami-Dade area have pets-35%
      of whom report needing pet evacuation assistance. However, GIS accessibility
      measures show that travel time factors are likely to impede older adults' use of
      the area's few pet-friendly shelters. Logistic regression results reveal that pet
      owners are less likely to report anticipating shelter use; however, the opposite
      holds for pet owners reporting they would need help evacuating their pets-they
      anticipate using shelters. Discussion: High pet shelter need coupled with low
      availability exacerbates older adults' heightened vulnerability during Florida's
      hurricane season.

PMID- 29029343
TI  - An Evaluation of Different Partitioning Strategies for Bayesian Estimation of
      Species Divergence Times.
AB  - The explosive growth of molecular sequence data has made it possible to estimate
      species divergence times under relaxed-clock models using genome-scale data sets
      with many gene loci. In order to improve both model realism and to best extract
      information about relative divergence times in the sequence data, it is important
      to account for the heterogeneity in the evolutionary process across genes or
      genomic regions. Partitioning is a commonly used approach to achieve those goals.
      We group sites that have similar evolutionary characteristics into the same
      partition and those with different characteristics into different partitions, and
      then use different models or different values of model parameters for different
      partitions to account for the among-partition heterogeneity. However, how to
      partition data in practical phylogenetic analysis, and in particular in relaxed
      clock dating analysis, is more art than science. Here, we use computer simulation
      and real data analysis to study the impact of the partition scheme on divergence
      time estimation. The partition schemes had relatively minor effects on the
      accuracy of posterior time estimates when the prior assumptions were correct and
      the clock was not seriously violated, but showed large differences when the clock
      was seriously violated, when the fossil calibrations were in conflict or
      incorrect, or when the rate prior was mis-specified. Concatenation produced the
      widest posterior intervals with the least precision. Use of many partitions
      increased the precision, as predicted by the infinite-sites theory, but the
      posterior intervals might fail to include the true ages because of the
      conflicting fossil calibrations or mis-specified rate priors. We analyzed a data
      set of 78 plastid genes from 15 plant species with serious clock violation and
      showed that time estimates differed significantly among partition schemes,
      irrespective of the rate drift model used. Multiple and precise fossil
      calibrations reduced the differences among partition schemes and were important
      to improving the precision of divergence time estimates. While the use of many
      partitions is an important approach to reducing the uncertainty in posterior time
      estimates, we do not recommend its general use for the present, given the
      limitations of current models of rate drift for partitioned data and the
      challenges of interpreting the fossil evidence to construct accurate and
      informative calibrations.

PMID- 29029346
TI  - Botanical Compound p-Anisaldehyde Repels Larval Lone Star Tick (Acari: Ixodidae),
      and Halts Reproduction by Gravid Adults.
AB  - The lone star tick, Amblyomma americanum (L.), widely distributed across eastern,
      southeastern, and midwestern regions of the United States and south into Mexico,
      is an obligate blood feeder that attaches to three hosts during the larval,
      nymphal, and adult stages. White-tailed deer and wild turkey are common hosts, as
      well as a wide variety of other avian and mammalian hosts. Amblyomma americanum
      is the most frequently reported species of tick to bite humans in the
      southeastern and southcentral United States, and it can transmit diseases that
      include erhlichiosis, rickettsiosis, tularemia, and protozoan infections. As A.
      americanum resistance to conventional insecticides becomes more common,
      alternative control tactics, such as application of bioactive botanical natural
      products are being investigated. p-Anisaldehyde has been found in many plant
      species and it has shown effects that include mortality, attractancy, and
      interference with host seeking. The series of bioassays we developed was
      effective for assessing a range of ixodid tick responses to chemicals. This first
      assessment of p-anisaldehyde on ticks focused mostly on larvae, usually the most
      vulnerable free-living stage, and on egg production by adults. Contact exposure
      to larvae resulted in an LD50 of 0.162% and an LD90 of 0.311% p-anisaldehyde.
      Although fumigation was not lethal to larval A. americanum, p-anisaldehyde was
      strongly repellent against them in several bioassays that indicate aspects of the
      repellency such as counteracting the negative geotaxic orientation on a vertical
      surface, the ability to trap larvae between and inside treatment barriers on
      different substrates and to divert upward larval movement from one surface to
      another, and the extent to which larvae fall from a treated surface. The compound
      at a relatively low concentration applied to gravid adults strongly reduces egg
      laying and the few eggs that are produced do not hatch. Aside from repelling
      larval A. americanum and halting reproduction, p-anisaldehyde has a variety of
      effects on other arthropods including attraction. Research on this compound as a
      potentially multifaceted pest management tool has been sparse. This study, for
      example, is the first to demonstrate p-anisaldehyde's repellent properties
      against an arthropod pest. p-Anisaldehyde might also act as a strong repellent
      against other tick species.

PMID- 29029344
TI  - The Clinical and Economic Impact of Attaining National HIV/AIDS Strategy
      Treatment Targets in the United States.
AB  - Background: The US National HIV/AIDS Strategy (NHAS) aims for 72% (90% diagnosed
      times 80% of those virally suppressed) viral suppression among persons with human
      immunodeficiency virus (HIV) by 2020. We examined the clinical and economic
      impact of reaching this target, in the general US population and among black men
      who have sex with men (MSM), the group with the highest HIV prevalence. Methods:
      Using a mathematical simulation, we project the 5- and 20-year clinical outcomes,
      costs, and incremental cost-effectiveness ratios for (1) Current Pace of
      detection, linkage, retention, and virologic suppression and (2) NHAS investments
      in expanded testing ($24-$74 per test) and adherence ($400 per person-year),
      calibrated to achieve 72% suppression by 2020. We examined alternative rates of
      testing, retention, and suppression and the efficacy and cost of adherence
      interventions. Results: Compared with Current Pace over 20 years, NHAS averted
      280000 HIV transmissions (80000 in black MSM) and 199000 (45000) deaths and saved
      2138000 (453000) years of life, while increasing costs by 23%. The incremental
      cost-effectiveness ratio for NHAS compared with Current Pace was $68900 per
      quality-adjusted life-year ($38300 for black MSM) and was most sensitive to
      antiretroviral therapy costs. Conclusions: Reaching NHAS targets would yield
      substantial clinical benefits and be cost-effective in both the general US and
      black MSM populations.

PMID- 29029347
TI  - Childhood Health and Educational Outcomes Associated With Maternal Sleep Apnea: A
      Population Record-Linkage Study.
AB  - Objectives: Sleep apnea in pregnancy is known to adversely affect birth outcomes.
      Whether in utero exposure to maternal sleep apnea is associated with long-term
      childhood consequences is unclear. Methods: Population-based longitudinal study
      of singleton infants born during 2002-2012 was conducted using linked birth,
      hospital, death, developmental, and educational records from New South Wales,
      Australia. Maternal sleep apnea during pregnancy was identified from hospital
      records. Outcomes were mortality and hospitalizations up to age 6, developmental
      vulnerability in the first year of school (aged 5-6 years), and performance on
      standardized tests in the third year of school (aged 7-9 years). Cox proportional
      hazards and modified Poisson regression models were used to calculate hazard and
      risk ratios for outcomes in children exposed to maternal apnea compared with
      those not exposed. Results: Two hundred nine of 626188 singleton infants were
      exposed to maternal sleep apnea. Maternal apnea was not significantly associated
      with mortality (Fisher's exact p = .48), developmental vulnerability (adjusted RR
      1.29; 95% CI 0.75-2.21), special needs status (1.58; 0.61-4.07), or low numeracy
      test scores (1.03; 0.63-1.67) but was associated with low reading test scores
      (1.55; 1.08-2.23). Maternal apnea significantly increased hospitalizations in the
      first year of life (adjusted HR 1.81; 95% CI 1.40-2.34) and between the first and
      sixth birthdays (1.41; 1.14-1.75). This is partly due to admissions for suspected
      pediatric sleep apnea. Conclusions: Maternal sleep apnea during pregnancy is
      associated with poorer childhood health. Its impact on developmental and
      cognitive outcomes warrants further investigation.

PMID- 29029348
TI  - Dysregulation of Sleep Behavioral States in Narcolepsy.
AB  - Study Objectives: Patients with narcolepsy experience poor maintenance of
      wakefulness and fragmented night sleep, but the underlying mechanism of sleep
      boundary dysregulation remains little understood. The goal of this study was to
      quantify abnormal sleep-wake regulation in narcolepsy patients. Methods: Using a
      model-based approach (state space analysis), we analyzed overnight
      electroencephalography recordings in 10 patients with narcolepsy type 1 and age-
      and gender-matched healthy control subjects. We analyzed consolidated sleep
      states using cluster analysis in state space and transitional sleep periods as
      trajectories between stable clusters. Results: Patients with narcolepsy showed a
      dislocation of rapid eye movement (REM) sleep in state space and overlap of REM
      and WAKE behavioral states. Narcolepsy patients had more trajectories between the
      REM and the WAKE clusters and also between the non-rapid eye movement (NREM) and
      WAKE clusters. Point density analysis showed more transitional periods between
      WAKE and REM in narcolepsy, less consolidated NREM sleep, and higher velocities
      between WAKE and NREM in patients. Conventional sleep analysis revealed increased
      NREM1 and decreased NREM2 sleep and reduced REM latency in narcolepsy patients.
      Conclusions: This study provides further evidence for narcolepsy as a disorder of
      state boundaries including but not limited to REM sleep and wakefulness. In
      particular, the increase in transitional periods between REM and WAKE but also
      between NREM and WAKE indicates abnormal state dynamics in narcolepsy. This
      pattern may be a consequence of disrupted sleep/wake stabilizing mechanisms due
      to loss of hypocretin/orexin neurons in the hypothalamus.

PMID- 29029349
TI  - Letter: Surgical Decision Making From Image-Based Biophysical Modeling of
      Glioblastoma: Not Ready for Primetime.

PMID- 29029350
TI  - The British Society for Rheumatology guideline for the management of systemic
      lupus erythematosus in adults.

PMID- 29029352
TI  - Patient Satisfaction Outcomes after Robotic Arm-Assisted Total Knee Arthroplasty:
      A Short-Term Evaluation.

PMID- 29029351
TI  - From the Cover: Development and Application of a Dual Rat and Human AHR
      Activation Assay.
AB  - Significant prolonged aryl hydrocarbon receptor (AHR) activation, classically
      exhibited following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin, can cause a
      variety of undesirable toxicological effects. Novel pharmaceutical chemistries
      also have the potential to cause activation of AHR and consequent toxicities in
      pre-clinical species and man. Previous methods either employed relatively
      expensive and low-throughput primary hepatocyte dosing with PCR endpoint, or low
      resolution overexpressing reporter gene assays. We have developed, validated and
      applied an in vitro microtitre plate imaging-based medium throughput screening
      assay for the assessment of endogenous species-specific AHR activation potential
      via detection of induction of the surrogate transcriptional target Cytochrome
      P450 CYP1A1. Routine testing of pharmaceutical drug development candidate
      chemistries using this assay can influence the chemical design process and
      highlight AHR liabilities. This assay should be introduced such that human AHR
      activation liability is flagged early for confirmatory testing.

PMID- 29029353
TI  - Centralization of Pediatric Surgery: European Perspective.

PMID- 29029354
TI  - Cost Analysis of Sending Routine Pathology Specimens following Total Joint
      Arthroplasty in the Age of Bundled Payments.
AB  - Bundled payment plans are being developed as a means to curb healthcare spending.
      Routine histology following total hip arthroplasties (THA) and total knee
      arthroplasties (TKA) is standard practice at many institutions. Recently, the
      value of this practice has been questioned as histologic diagnoses in THA and TKA
      rarely differ from the clinical diagnoses. The goal of this study is to identify
      discrepant and discordant diagnoses following THA and TKA at an academic medical
      center and to calculate the cost-saving potential in the setting of a bundled
      payment plan. A retrospective chart review was conducted on 1,213 primary THA and
      TKA performed by two orthopaedic surgeons from 2012 to 2014. The clinical and
      histologic diagnoses were compared and classified as concordant, discrepant, or
      discordant. Cost information was obtained from the institutional billing office.
      One thousand one hundred and sixty-six THA and TKA were analyzed in the final
      cohort. Nineteen (1.6%) diagnoses were classified as discrepant while none were
      discordant. The cost of histologic examination per specimen was estimated to be
      $48.56. The total cost of all arthroplasties was $14,999,512.46, of which
      histologic examination made up 0.31% of the total cost. The results of this study
      corroborate the results of previous studies and support the proposition that
      routine histologic examination is not cost-effective. The cost incurred to
      perform histologic examination will become a cost deduction from future bundled
      payments. The practice of sending routine histologic specimens following TJA
      should be decided upon by the operating orthopaedic surgeon.

PMID- 29029355
TI  - Over-Sewing of Staple Line in Laparoscopic Sleeve Gastrectomy: Initial Experience
      of a Comparative Study.
AB  - INTRODUCTION: The main drawback of laparoscopic sleeve gastrectomy (LSG) is the
      severity of postoperative complications. Staple line reinforcement (SLR) is
      strongly advocated. Recently, over-sewing has been proposed as a cost-effective
      and helpful method for reinforcing the staple line. The purpose of this study was
      to report our initial experience with LSG comparing over-sewing over the entire
      staple line with the upper-third staple line. MATERIALS AND METHODS: All obese
      patients seen at Negrar Sacro Cuore, Don Calabria Hospital were entered into our
      prospective database and were retrospectively evaluated. Complications (divided
      as major complications: leaks and bleeding; and minor complications: dysphagia,
      esophagitis, and reflux disease) and reoperations were recorded for all patients.
      Complications were graded according to the Clavien classification system.
      RESULTS: From February 2015 to March 2016, 30 patients underwent LSG. Patients
      were divided in two groups according to over-sewing: Group A-over-sewing over the
      entire staple line; and Group B upper-third over-sewing. Mean total operative
      time was longer in Group A-90 minutes-compared with 85 minutes in Group B. In
      regard to minor complications, we reported one esophagitis and two cases of
      dysphagia in Group B and one dysphagia in Group A. Gastroesophageal reflux was
      higher in Group B than in Group A (3 vs. 1, p=0.149). Three major complications
      were observed (10%): two bleeding and one hematoma in Group B and no major
      complications occurred in Group A. All major complications were conservatively
      treated. No leaks were reported in both groups. No mortality was observed.
      CONCLUSIONS: Over-sewing of the staple line was associated with fewer leaks but
      no conclusions can be drawn regarding the effects of over-sewing on staple line
      bleedings. Before standardizing surgical techniques further, trials are necessary
      to improve our knowledge about over-sewing in LSG.

PMID- 29029356
TI  - Total Hip Arthroplasty Dislocation after Cardioversion: A Case Report.
AB  - New onset postoperative atrial fibrillation (AF) is the most common perioperative
      arrhythmia in the elderly. The incidence after total joint arthroplasty is much
      lower than other non-cardiac surgeries. Since postoperative atrial fibrillation
      can cause increased length of hospital stay, mortality, and healthcare costs, it
      is critical to focus on prevention and prompt management. New onset atrial
      fibrillation is treated with rhythm control for patients who demonstrate
      hemodynamic instability or refractory to rate control measures. Electrical
      cardioversion is an effective option for unstable patients with known
      complications. However, there is limited data on orthopedic problems after
      cardioversion. A unique case is reported presenting postoperative total hip
      arthroplasty (THA) dislocation after electrical cardioversion for new onset
      atrial fibrillation in the postanesthesia care unit (PACU).

PMID- 29029357
TI  - A Pilot Retrospective Study to Evaluate Two Multi-Layer Foam Dressings for the
      Management of Moderately Exudative Pressure Injuries.
AB  - Prevention and treatment of pressure injuries (PI) is a standard benchmark for
      quality of care, performance, risk reduction, and patient safety. Foam dressings
      are designed to wick away a large volume of exudate with minimal lateral movement
      to prevent periwound skin maceration; this renders foam dressings a popular
      choice for the treatment of chronic wounds with high to moderate amounts of
      exudate. In addition, multi-layer foam dressings may have added benefits to
      alleviate pressure and minimize shear as the dressing materials slide against
      each other. The purpose of this retrospective pilot study was to evaluate the
      effectiveness and safety of two different multi-layer foam dressings (Optifoam(r)
      Gentle, Medline Industries, Inc. Northfield, Illinois; Mepilex(r) Border,
      Molnlycke Health Care, Gothenburg, Sweden) for the management of pressure
      injuries that produce a moderate amount of exudate. A total of 15 patients and 25
      wound treatments were reviewed over a period of 12 months in the study. The
      difference in the mean surface areas at baseline between the two dressings was
      not statistically significant (p=.38). All wounds improved over time. There was
      no difference in healing rate (cm2/day) for wounds that were treated with the
      Mepilex(r) Border dressing (M=.12 cm2/day, SD=.19) compared to the Optifoam(r)
      Gentle dressing (M=.18 cm2/day; SD=.25); t (23)= .85, p=.40. Findings of this
      study suggest similar clinical performance between the two foam dressings. Foam
      dressings were used for the management of several shallow stage 3 and 4 PIs in
      place of packing. Results of this study challenge the commonly accepted notion
      that wounds with depth should always be packed with dressing material.

PMID- 29029358
TI  - Topographical Variations between Splenic Flexure and Spleen: A Study with CT
      Image-Based Reconstruction.
AB  - INTRODUCTION: An issue that is seldom seen in the literature relates the detailed
      relationship of the splenic flexure (SF) and the spleen-both carefully examined
      with a prospective approach in patients undergoing computer tomography (CT) scan.
      MATERIALS AND METHODS: SF localization has been searched and examined in 120
      consecutive CT scans. Several different variables (age, gender, BMI, indication
      of CT scan, etc.) have been considered. In cooperation with the Radiology
      Division, we brought to completion a dedicated topographic outline, with the
      purpose of providing a detailed classification for SF localization. RESULTS: The
      SF lies, in 52% of cases, in what we called the inferior (I) position, below the
      spleen. Other categories of our classification were anterior (A) and posterior
      (P) positions, which were found respectively in 42% and 8% of analyzed cases.
      Considering all the variables given, we did not find any significant statistical
      correlation (p > 0.05). CONCLUSIONS: This study was carried out to classify types
      of SF in terms of its positional relationship with the spleen. We investigated
      120 CT scans and classified the SF into three types, according to its
      localization: inferior (I), anterior (A), and posterior (P) types. A better
      understanding of the anatomic variability in SF may be useful for minimizing
      complications and performing an accurate surgical dissection.

PMID- 29029359
TI  - A probabilistic network for the diagnosis of acute cardiopulmonary diseases.
AB  - In this paper, the development of a probabilistic network for the diagnosis of
      acute cardiopulmonary diseases is presented in detail. A panel of expert
      physicians collaborated to specify the qualitative part, which is a directed
      acyclic graph defining a factorization of the joint probability distribution of
      domain variables into univariate conditional distributions. The quantitative
      part, which is a set of parametric models defining these univariate conditional
      distributions, was estimated following the Bayesian paradigm. In particular, we
      exploited an original reparameterization of Beta and categorical logistic
      regression models to elicit the joint prior distribution of parameters from
      medical experts, and updated it by conditioning on a dataset of hospital records
      via Markov chain Monte Carlo simulation. Refinement was iteratively performed
      until the probabilistic network provided satisfactory concordance index values
      for several acute diseases and reasonable diagnosis for six fictitious patient
      cases. The probabilistic network can be employed to perform medical diagnosis on
      a total of 63 diseases (38 acute and 25 chronic) on the basis of up to 167
      patient findings.

PMID- 29029360
TI  - Laser desorption ionization mass spectrometry: Recent progress in matrix-free and
      label-assisted techniques.
AB  - The MALDI-based mass spectrometry, over the last three decades, has become an
      important analytical tool. It is a gentle ionization technique, usually
      applicable to detect and characterize analytes with high molecular weights like
      proteins and other macromolecules. The earlier difficulty of detection of
      analytes with low molecular weights like small organic molecules and metal ion
      complexes with this technique arose due to the cluster of peaks in the low
      molecular weight region generated from the matrix. To detect such molecules and
      metal ion complexes, a four-prong strategy has been developed. These include use
      of alternate matrix materials, employment of new surface materials that require
      no matrix, use of metabolites that directly absorb the laser light, and the laser
      absorbing label-assisted LDI-MS (popularly known as LALDI-MS). This review will
      highlight the developments with all these strategies with a special emphasis on
      LALDI-MS.

PMID- 29029361
TI  - The mechanism of attenuation of epithelial-mesenchymal transition by a
      phosphodiesterase 5 inhibitor via renal klotho expression.
AB  - Phosphodiesterase-5 (PDE-5) inhibitors induces vasodilation in several organs by
      blocking cyclic GMP (guanosine monophosphate) degradation. However, the existence
      of alternative mechanism of action in case of an impaired nitric oxide (NO)
      system remains controversial. Previous studies suggested that decreased NO
      bioavailability may result in the downregulation of klotho expression, but the
      relationship between klotho and NO remains obscure. Therefore, we investigated
      whether a PDE-5 inhibitor could preserve epithelial-mesenchymal transition (EMT)
      and relationship exists between the NO and renal klotho expression. Ten-week-old
      SD rats (N = 24, 200 g, male) were divided (N = 6) into four groups, which
      received: A LSD, L-NAME 1 mg/mL in drinking water, Udenafil 5 mg/kg
      subcutaneously and both for 4 weeks. Urine nitrate/nitrite, NGAL (Neutrophil
      gelatinase-associated lipocalin), and cGMP were measured using ELISA. Kidney was
      subjected to evaluate PCNA (proliferative cell nuclear antigen), alpha-SMA
      (smooth muscle cell antigen), E-cadherin, and klotho expression. Urine cGMP
      decreased after treatment of PDE-5 inhibitor compared with control due to
      blocking degradation of cGMP (P < .05, control vs Udenafil and L-NAME with
      Udenafil groups). Urine NGAL increased after treating of L-NAME and attenuated
      after using PDE-5 inhibitor (P < .05, control vs L-NAME and L-NAME with
      Udenafil). PCNA, alpha-SMA, and E-cadherin (EMT markers) increased after L-NAME
      treatment and normalized after using PDE-5 inhibitor. Klotho expression showed
      trend to increase in the L-NAME with PDE-5 inhibitor group compared with the L
      NAME group, however, eNOS expression did not change after treatment of L-NAME or
      PDE-5 inhibitor compared with control. PDE-5 inhibitor alleviates EMT in the
      kidney via klotho modulation independent of the NO system.

PMID- 29029362
TI  - Altered TDP-43-dependent splicing in HSPB8-related distal hereditary motor
      neuropathy and myofibrillar myopathy.
AB  - BACKGROUND AND PURPOSE: Mutations in the small heat-shock protein 22 gene (HSPB8)
      have been associated with Charcot-Marie-Tooth disease type 2L, distal hereditary
      motor neuropathy (dHMN) type IIa and, more recently, distal myopathy/myofibrillar
      myopathy (MFM) with protein aggregates and TDP-43 inclusions. The aim was to
      report a novel family with HSPB8K141E -related dHMN/MFM and to investigate, in a
      patient muscle biopsy, whether the presence of protein aggregates was paralleled
      by altered TDP-43 function. METHODS: We reviewed clinical and genetic data. We
      assessed TDP-43 expression by qPCR and alternative splicing of four previously
      validated direct TDP-43 target exons in four genes by reverse transcriptase
      polymerase chain reaction. RESULTS: The triplets and their mother presented in
      the second to third decade of life with progressive weakness affecting distal and
      proximal lower limb and truncal muscles. Nerve conduction study showed a motor
      axonal neuropathy. The clinical features, moderately raised creatin kinase
      levels, selective pattern of muscle involvement on magnetic resonance imaging and
      pathological changes on muscle biopsy, including the presence of protein
      aggregates, supported the diagnosis of a contemporary primary muscle involvement.
      In affected muscle tissue we observed a consistent alteration of TDP-43-dependent
      splicing in three out of four TDP-43-target transcripts (POLDIP3, FNIP1 and
      BRD8), as well as a significant decrease of TDP-43 mRNA levels. CONCLUSIONS: Our
      study confirmed the role of mutated HSPB8 as a cause of a combined neuromuscular
      disorder encompassing dHMN and MFM with protein aggregates. We identified
      impaired RNA metabolism, secondary to TDP-43 loss of function, as a possible
      pathological mechanism of HSPB8K141E toxicity, leading to muscle and nerve
      degeneration.

PMID- 29029363
TI  - Synergistic induction of astrocytic differentiation by factors secreted from
      meninges in the mouse developing brain.
AB  - Astrocytes, which support diverse neuronal functions, are generated from
      multipotent neural stem/precursor cells (NS/PCs) during brain development.
      Although many astrocyte-inducing factors have been identified and studied in
      vitro, the regions and/or cells that produce these factors in the developing
      brain remain elusive. Here, we show that meninges-produced factors induce
      astrocytic differentiation of NS/PCs. Consistent with the timing when astrocytic
      differentiation of NS/PCs increases, expression of astrocyte-inducing factors is
      upregulated. Meningeal secretion-mimicking combinatorial treatment of NS/PCs with
      bone morphogenetic protein 4, retinoic acid and leukemia inhibitory factor
      synergistically activate the promoter of a typical astrocytic marker, glial
      fibrillary acidic protein. Taken together, our data suggest that meninges play an
      important role in astrocytic differentiation of NS/PCs in the developing brain.

PMID- 29029364
TI  - Ecm33 is a novel factor involved in efficient glucose uptake for nutrition
      responsive TORC1 signaling in yeast.
AB  - Glucose uptake is crucial for providing both an energy source and a signal that
      regulates cell proliferation. Therefore, it is important to clarify the
      mechanisms underlying glucose uptake and its transmission to intracellular
      signaling pathways. In this study, we searched for a novel regulatory factor
      involved in glucose-induced signaling by using Saccharomyces cerevisiae as a
      eukaryotic model. Requirement of the extracellular protein Ecm33 in efficient
      glucose uptake and full activation of the nutrient-responsive TOR kinase complex
      1 (TORC1) signaling pathway is shown. Cells lacking Ecm33 elicit a series of
      starvation-induced pathways even in the presence of extracellular high glucose
      concentration. This results in delayed cell proliferation, reduced ATP, induction
      of autophagy, and dephosphorylation of the TORC1 substrates Atg13 and Sch9.

PMID- 29029365
TI  - Eighteen-month lamivudine prophylaxis on preventing occult hepatitis B virus
      infection reactivation in patients with haematological malignancies receiving
      immunosuppression therapy.
AB  - This study evaluated the long-term efficacy and safety of an 18-month lamivudine
      prophylaxis in 68 HBsAg-negative/anti-HBc-positive patients with
      oncohaematological disease. All 68 consecutive HBsAg-negative/anti-HBc-positive
      patients with an oncohaematological disease and naive for chemotherapy observed
      from April 2008 to December 2012 at 2 Hematology Units in Naples were treated
      with lamivudine for 18 months after stopping chemotherapy and monitored for HBsAg
      at months 1 and 3 during chemotherapy and then every 3 months after its
      discontinuation. During follow-up, 13 (19.1%) of the 68 patients died of
      complications related to their oncohaematological disease, and 3 (4%) showed a
      virological HBV reactivation (retroconversion to HBsAg positivity) 1-7 months
      after the discontinuation of lamivudine prophylaxis (2 treated for chronic
      lymphocytic leukaemia and one for Waldenstrom's disease); of these, 2 showed a
      biochemical reactivation. Comparing the demographic and clinical characteristics
      of the 3 patients with a virological HBV reactivation to the 65 without, the
      former were older (median age and range: 67 years [75-78] vs. 61 [24-88]; P =
      .05) and were less frequently treated for B-cell non-Hodgkin lymphoma (B-NHL) (0
      vs. 70.7%, P = .03). In conclusion, a 18 months of lamivudine prophylaxis was
      effective in preventing HBV reactivation in HBsAg-negative/anti-HBc-positive
      patients treated for B-NHL. However, in patients with chronic and severe
      immunodepression, such as those with chronic lymphocytic leukaemia and
      Waldenstrom's disease, prophylaxis should be continued for an indefinite period.

PMID- 29029366
TI  - Directly Coupled Versus Spectator Linkers on Diimine PtII Acetylides-Change the
      Structure, Keep the Function?
AB  - Modification of light-harvesting units with anchoring groups for surface
      attachment often compromises light-harnessing properties. Herein, a series of
      [donor-acceptor-anchor] platinum(II) diimine (bis-)acetylides was developed in
      order to systematically compare the effect of conjugated versus electronically
      decoupled modes of attachment of protected anchoring groups on the photophysical
      properties of light-harvesting units. The first examples of "decoupled"
      phosphonate diimine PtII complexes are reported, and their properties are
      compared and contrasted to those of carboxylate analogues studied by a diversity
      of methods. Ultrafast time-resolved IR and transient absorption spectroscopy
      revealed that all complexes have a charge-transfer (CT) lowest excited state with
      lifetimes between 2 and 14 ns. Vibrational signatures and dynamics of CT states
      were identified; the assignment of electronic states and their vibrational origin
      was aided by TDDFT calculations. Ultrafast energy redistribution accompanied by
      structural changes was directly captured in the CT states. A significant
      difference between the structures of the electronic ground and CT excited states,
      as well as differences in the structural reorganisation in the complexes bearing
      directly attached or electronically decoupled anchoring groups, was discovered.
      This work demonstrates that decoupling of the anchoring group from the light
      harvesting core by a saturated spacer is an easy approach to combine surface
      attachment with high reduction potential and ten times longer lifetime of the CT
      excited state of the light-absorbing unit, and retain electron-transfer
      photoreactivity essential for light-harvesting applications.

PMID- 29029367
TI  - Genetic diversity of Plasmodium falciparum merozoite surface protein-1 (block 2),
      glutamate-rich protein and sexual stage antigen Pfs25 from Chandigarh, North
      India.
AB  - OBJECTIVE: To elucidate the genetic diversity of Plasmodium falciparum in
      residual transmission foci of northern India. METHODS: Clinically suspected
      patients with malaria were screened for malaria infection by microscopy. 48 P.
      falciparum-infected patients were enrolled from tertiary care hospital in
      Chandigarh, India. Blood samples were collected from enrolled patients, genomic
      DNA extraction and nested PCR was performed for further species confirmation.
      Sanger sequencing was carried out using block 2 region of msp1, R2 region of
      glurp and pfs25-specific primers. RESULTS: Extensive diversity was found in msp1
      alleles with predominantly RO33 alleles. Overall allelic prevalence was 55.8% for
      RO33, 39.5% for MAD20 and 4.7% for K1. Six variants were observed in MAD20,
      whereas no variant was found in RO33 and K1 alleles. A phylogenetic analysis of
      RO33 alleles indicated more similarity to South African isolates, whereas MAD20
      alleles showed similarity with South-East Asian isolates. In glurp, extensive
      variation was observed with eleven different alleles based on the AAU repeats.
      However, pfs25 showed less diversity and was the most stable among the targeted
      genes. CONCLUSION: Our findings document the genetic diversity among circulating
      strains of P. falciparum in an area of India with low malaria transmission and
      could have implications for control strategies to reach the national goal of
      malaria elimination.

PMID- 29029368
TI  - Who accesses surgery at district level in sub-Saharan Africa? Evidence from
      Malawi and Zambia.
AB  - OBJECTIVES: To examine age and gender distribution for the most common types of
      surgery in Malawi and Zambia. METHODS: Data were collected from major operating
      theatres in eight district hospitals in Malawi and nine in Zambia. Raw data on
      surgical procedures were coded by specialist surgeons for frequency analyses.
      RESULTS: In Malawi female surgical patients had a mean age of 25 years, with 91%
      aged 16-40 years. Females accounted for 85%, and obstetric cases for 75%, of all
      surgical patients. In Zambia, female surgical patients had a mean age of 26, with
      75% aged 16-40 years. They accounted for 55% of all cases, 34% being obstetric.
      Male surgical patients in Malawi were on average older (33 years) than in Zambia
      (23 years). General surgical cases in men and women, respectively, had a median
      age of 42 and 32 in Malawi and 26 and 30 in Zambia. The median age of trauma
      patients was 12 in males and 10 in females in both countries. Children aged 0-15
      years accounted for 64-65% of all trauma cases in Malawi and 57-58% in Zambia,
      with peak incidences in 6- to 10-year-olds. CONCLUSIONS: Women of reproductive
      (16-45 years) mainly undergoing Caesarean sections and children aged 0-15 years
      who accounted for two-thirds of trauma cases are the main patient populations
      undergoing surgery at district hospitals in Zambia and Malawi. Verification and
      analysis of routine hospital data, across 10-30% of districts countrywide,
      demonstrated the need to prioritise quality assurance in surgery and anaesthesia,
      and preventive interventions in children.

PMID- 29029370
TI  - Elder neglect-Oral diseases and injuries.
AB  - Elder neglect (EN) is the failure of a designated caregiver to meet the needs of
      a dependent older person. World EN prevalence, meta-analyzed in this study, is
      1.0% or 1.8% according to different statistical methods. Referring alleged EN
      cases to Adult Protective Services (APSs) by healthcare workers (HCWs) is
      mandatory in many countries. However, only few claims are substantiated, as EN
      could be confused with Self-Neglect, and neglect could be unintentional or due to
      caregiver unawareness. Screening tools are inaccurate, and their use is
      discouraged by public health organizations, because they lead to too many false
      positives, which engulf the already overwhelmed APSs. HCWs need effective tools
      with objective judgments, which do not hamper the HCW-caregiver-patient rapport
      and prevent lawsuits when allegations are unfounded. Orofacial EN manifestations
      (poor oral/denture hygiene, lack of needed/improper dentures, dry mouth,
      skin/mucosal rashes) are essential Forensic Markers of EN. I classified EN
      associated oral diseases according to the unmet needs into four groups: (1)
      traumatic injuries due to lack of caregiver vigilance (e.g., maxillofacial
      fractures); (2) diseases due to oral hygiene deficiency (e.g., root caries); (3)
      diseases typical of the elderly with late/no diagnosis (e.g., oral cancer); and
      (4) diseases typical of the elderly exacerbated by psychological distress (e.g.,
      oral lichen planus).

PMID- 29029371
TI  - Structures of a Complex Hydrazinium Lead Iodide, (N2 H5 )15 Pb3 I21 , Possessing
      [Pb2 I9 ]5- , [PbI6 ]4- , and I- Ions and alpha- and beta-(N2 H5 )PbI3.
AB  - Photovoltaic perovskites, most notably methylammonium lead triiodide, (NH3
      Me)PbI3 , have recently attracted considerable attention, and based upon the
      modified "Goldschmidt" as well as a "revised" tolerance factors, hydrazinium
      should be able to occupy the same cation site as methylammonium, and form a cubic
      unit cell. The reaction of N2 H5+ I- with PbI2 in dimethylformamide results in
      three types of yellow crystals; hexagonal, needle-like, and rod-like, the
      structures of which were determined at 100 K. The hexagonal (P63 /m:
      a=10.8906(10) A; b=37.845(5) A) crystals possess isolated face-sharing octahedral
      [Pb2 I9 ]5- , [PbI6 ]4- , and I- ions. IR spectroscopy indicates the presence of
      hydrogen-bonded N2 H5+ and the composition was determined by single-crystal X-ray
      diffraction, density measurements, combustion elemental analysis, and
      thermogravimetric analysis to be (N2 H5 )15 Pb3 I21 , which is photoluminescent
      at 50 K, but not at room temperature. The needle and rod crystals have an
      orthorhombic (Pnma: a=11.1385(7) A; b=4.4806(3) A; c=17.6241(11) A) and hexagonal
      (P63 /mmc: a=8.7386(9) A; b=8.2006(9) A) unit cells, respectively, possessing the
      perovskite ABX3 composition of (N2 H5 )PbI3 , but neither exhibits the cubic
      Perovskite structure type. The structures of alpha- and beta-(N2 H5 )PbI3 possess
      parallel ribbons of Pb2 I4 and chains of PbI2 , respectively. Strong inter
      hydrazinium hydrogen bonding due to it possessing both hydrogen bonding donor and
      acceptor sites (unlike NH3 Me+ ) appear to stabilize the observed extended ribbon
      motif for (N2 H5 )15 Pb3 I21 and alpha-(N2 H5 )PbI3 . (N2 H5 )15 Pb3 I21 has a
      band-gap-like absorption of 2.34 eV, and both alpha- and beta-(N2 H5 )PbI3 have a
      2.70 eV band-gap-like absorptions.

PMID- 29029373
TI  - Meet NPInfluence, an exclusive panel of nurse practitioner opinion leaders
      impacting the future of health care.

PMID- 29029369
TI  - No disparity of the efficacy and all-cause mortality between Asian and non-Asian
      type 2 diabetes patients with sodium-glucose cotransporter 2 inhibitors
      treatment: A meta-analysis.
AB  - AIMS/INTRODUCTION: To evaluate whether there is disparity of the efficacy and all
      cause mortality and other adverse effects between Asian and non-Asian patients
      with sodium-glucose cotransporter 2 (SGLT2) inhibitors treatment. MATERIALS AND
      METHODS: Randomized clinical trials publicly available before January 2017,
      comparing SGLT2 inhibitors treatment with a placebo in type 2 diabetes patients
      were identified. The association between treatment and outcomes was estimated by
      computing the weighted mean difference for glycated hemoglobin level, blood
      pressure level, lipid profile levels and bodyweight, and the odds ratios for
      adverse events. RESULTS: A total of 17 trials with Asian patients were included
      and 39 trials with non-Asian patients were included. Comparison of the glycated
      hemoglobin decreases corrected by a placebo between Asian and non-Asian patients
      showed that there was a non-significant difference of 0.05% between groups (P >
      0.05). Comparisons of the bodyweight changes and blood pressure changes corrected
      by a placebo between Asian and non-Asian patients did not show a significant
      difference between groups (P > 0.05). The risk of all-cause mortality was not
      increased when compared with a placebo both in Asian and non-Asian populations,
      and the risk of genital infection in Asian and non-Asian populations were both
      significant increased. CONCLUSIONS: Overall, according to the present meta
      analysis, comparison of the efficacy in SGLT2 inhibitors treatment between Asian
      and non-Asian type 2 diabetes patients showed no significant difference in
      glycated hemoglobin reduction and bodyweight reduction. Furthermore, no disparity
      was found in the risk of all-cause mortality or hypoglycemia in SGLT2 inhibitors
      treatment between Asian and non-Asian patients.

PMID- 29029374
TI  - A look at some changes in publishing infrastructure.

PMID- 29029376
TI  - AANP News.

PMID- 29029375
TI  - Treatment and disease management of multiple sclerosis patients: A review for
      nurse practitioners.
AB  - BACKGROUND AND PURPOSE: This review discusses the role of the nurse practitioner
      (NP) in evaluating the clinical effects, potential side effects, and monitoring
      requirements for treatment options in multiple sclerosis (MS) and provides
      guidance on how to help patients understand these issues. METHODS: A literature
      search was conducted on PubMed to identify publications on monitoring and disease
      management of MS patients. Additional resources included drug information web
      sites and package inserts. CONCLUSIONS: NPs play an active role in the management
      of MS patients via effective monitoring and communication throughout the
      patient's treatment regimen and disease course. In the shared decision-making
      model of MS treatment, NPs ensure that patients understand the implications of
      their disease-modifying therapies (DMTs). As patients move through treatments
      during the course of their disease, the importance of this role increases, and it
      is critical that NPs follow the guidelines in each medication's product label and
      take into account any potential lingering effects of prior medications.
      IMPLICATIONS FOR PRACTICE: It is critical for NPs to promote patient adherence,
      to ensure that patients understand treatment side effects and monitoring
      requirements, and to take sequencing and reversibility implications of DMTs into
      account when making clinical decisions.

PMID- 29029377
TI  - Gain-of-function mutations in G-protein-coupled receptor genes associated with
      human endocrine disorders.
AB  - The human genome encodes more than 700 G-protein-coupled receptors (GPCRs), many
      of which are involved in hormone secretion. To date, more than 100 gain-of
      function (activating) mutations in at least ten genes for GPCRs, in addition to
      several loss-of-function mutations, have been implicated in human endocrine
      disorders. Previously reported gain-of-function GPCR mutations comprise various
      missense substitutions, frameshift mutations, intragenic inframe deletions and
      copy-number gains. Such mutations appear in both germline and somatic tumour
      cells, and lead to various hormonal abnormalities reflecting excessive receptor
      activity. Phenotypic consequences of these mutations include distinctive
      endocrine syndromes, as well as relatively common hormonal abnormalities. Such
      mutations encode hyperfunctioning receptors with increased constitutive activity,
      broadened ligand specificity, increased ligand sensitivity and/or delayed
      receptor desensitization. Furthermore, recent studies proposed a paradoxical gain
      of-function mechanism caused by inactive GPCR mutants. Molecular diagnosis of
      GPCR activating mutations serves to improve the clinical management of mutation
      positive patients. This review aims to introduce new aspects regarding gain-of
      function mutations in GPCR genes associated with endocrine disorders.

PMID- 29029378
TI  - Gpn3 is polyubiquitinated on lysine 216 and degraded by the proteasome in the
      cell nucleus in a Gpn1-inhibitable manner.
AB  - Gpn1 associates with Gpn3, and both are required for RNA polymerase II nuclear
      targeting. Global studies have identified by mass spectrometry that human Gpn3 is
      ubiquitinated on lysines 189 and 216. Our goals here were to determine the type,
      physiological importance, and regulation of Gpn3 ubiquitination. After inhibiting
      the proteasome with MG132, Gpn3-Flag was polyubiquitinated on K216, but not K189,
      in HEK293T cells. Gpn3-Flag exhibited nucleo-cytoplasmic shuttling, but
      polyubiquitination and proteasomal degradation of Gpn3-Flag occurred only in the
      cell nucleus. Polyubiquitination-deficient Gpn3-Flag K216R displayed a longer
      half-life than Gpn3-Flag in two cell lines. Interestingly, Gpn1-EYFP inhibited
      Gpn3-Flag polyubiquitination in a dose-dependent manner. In conclusion, Gpn1
      inhibitable, nuclear polyubiquitination on lysine 216 regulates the half-life of
      Gpn3 by tagging it for proteasomal degradation.

PMID- 29029379
TI  - Role of 24-epibrassinolide (EBL) in mediating heavy metal and pesticide induced
      oxidative stress in plants: A review.
AB  - Industrialization and urbanization have posed serious threats to the environment.
      Excessive release of heavy metals from industrial effluents and overuse of
      pesticides in modern agriculture are limiting crop production by polluting
      environment and deteriorating food quality. Sustaining food quality under heavy
      metals and pesticide stress is crucial to meet the increasing demands for food.
      24-Epibrassinolide (EBL), a ubiquitously occurring plant growth hormone shows
      great potential to alleviate heavy metals and pesticide stress in plants. This
      review sums up the potential role of EBL in ameliorating heavy metals and
      pesticide toxicity in plants extensively. EBL application increases plant's
      overall growth, biomass accumulation and photosynthetic efficiency by the
      modulation of numerous biochemical and physiological processes under heavy metals
      and pesticide stress. In addition, EBL scavenges reactive oxygen species (ROS) by
      triggering the production of antioxidant enzymes such as SOD, CAT, POX etc. EBL
      also induces the production of proline and soluble proteins that helps in
      maintaining osmotic potential and osmo-protection under both heavy metals and
      pesticide stress. At the end, future needs of research about the application of
      24-epibrassinolide have also been discussed.

PMID- 29029380
TI  - Is the microcosm approach using meiofauna community descriptors a suitable tool
      for ecotoxicological studies?
AB  - The usual approaches used in ecological risk assessment have been based on
      individual and population level standard procedures. Although these have been
      important tools to assess adverse effects on ecosystems, they are generally
      simplified and therefore lack ecological realism. Microcosm studies using
      meiobenthic communities offer a good compromise between the complexity of the
      ecosystem and the often highly artificial settings of laboratory experiments. An
      experiment was designed to investigate the potential of the microcosm approach
      using meiofauna as a tool for ecotoxicological studies. The experiment tested the
      ecological effects of exposure to sewage-impacted pore water simultaneously at
      the community level using meiofauna microcosms and at the individual level using
      laboratory fecundity tests with the copepod Nitokra sp. Specifically, the
      experiment tested the toxicity of pore water from three sites according to a
      contamination gradient. Both approaches were efficient in detecting differences
      in toxicity between the less and more contaminated sites. However, only
      multivariate data from community analysis detected differences in the gradient of
      contamination. In addition to information about toxicity, the community level
      microcosm experiment gave indications about sensitive and tolerant species,
      indirect ecological effects, as well as raised hypothesis about contamination
      routes and bioavailability to be tested. Considering the importance of meiofauna
      for benthic ecosystems, the microcosm approach using natural meiobenthic
      communities might be a valuable addition as a higher tier approach in ecological
      risk assessment, providing highly relevant ecological information on the toxicity
      of contaminated sediments.

PMID- 29029381
TI  - Biochemical responses and accumulation patterns of Mytilus galloprovincialis
      exposed to thermal stress and Arsenic contamination.
AB  - Organisms in marine systems are exposed to multiple stressors that create a range
      of associated environmental and ecotoxicological risks. Examples of stressors
      include alterations related to climate change, such as temperature increase, and
      the exposure to pollutants arising from human activities. The present study
      evaluated the impacts of Arsenic exposure (1mg/L) and warming (21 degrees C) in
      Mytilus galloprovincialis, acting alone and in combination. Our results
      demonstrated that both Arsenic exposure and warming induced oxidative stress and
      reduced mussels metabolism, with changes becoming more prominent with the
      exposure time and when mussels were exposed to both stressors in combination.
      Furthermore, results obtained showed higher As accumulation in organisms exposed
      to warming treatments. The present study showed that under warming scenarios, the
      negative impacts induced by As may be enhanced in ecologically and economically
      relevant bivalves, with potential impacts on population stocks due to increased
      sensitivity to pollutants, which may eventually result in biodiversity loss and
      socio-economic impacts.

PMID- 29029382
TI  - Differential impacts of six insecticides on a mealybug and its coccinellid
      predator.
AB  - Broad-spectrum insecticides may disrupt biological control and cause pest
      resurgence due to their negative impacts on natural enemies. The preservation of
      sustainable pest control in agroecosystems requires parallel assessments of
      insecticide toxicity to target pests and their key natural enemies. In the
      present study, the leaf dipping method was used to evaluate the relative toxicity
      of six insecticides to the striped mealybug, Ferrisia dasylirii (Cockerell)
      (Hemiptera: Pseudococcidae) and its predator, Tenuisvalvae notata (Mulsant)
      (Coleoptera: Coccinellidae). Three neurotoxic insecticides, lambda-cyhalothrin,
      methidathion and thiamethoxam, caused complete mortality of both pest and
      predator when applied at their highest field rates. In contrast, lufenuron,
      pymetrozine and pyriproxyfen caused moderate mortality of third-instar mealybug
      nymphs, and exhibited low or no toxicity to either larvae or adults of the lady
      beetle. At field rates, lufenuron and pymetrozine had negligible effects on prey
      consumption, development or reproduction of T. notata, but adults failed to
      emerge from pupae when fourth instar larvae were exposed to pyriproxyfen. In
      addition, pyriproxyfen caused temporary sterility; T. notata females laid non
      viable eggs for three days after exposure, but recovered egg fertility
      thereafter. Our results indicate that the three neurotoxic insecticides can
      potentially control F. dasylirii, but are hazardous to its natural predator. In
      contrast, lufenuron and pymetrozine appear compatible with T. notata, although
      they appear less effective against the mealybug. Although the acute toxicity of
      pyriproxyfen to T. notata was low, some pupal mortality and reduced egg fertility
      suggest that this material could impede the predator's numerical response to
      mealybug populations.

PMID- 29029383
TI  - DPP4 inhibition prevents AKI.

PMID- 29029384
TI  - p53 upregulates PLCepsilon-IP3-Ca2+ pathway and inhibits autophagy through its
      target gene Rap2B.
AB  - The tumor suppressor p53 plays a pivotal role in numerous cellular responses as
      it regulates cell proliferation, metabolism, cellular growth, and autophagy. In
      order to identify novel p53 target genes, we utilized an unbiased microarray
      approach and identified Rap2B as a robust candidate, which belongs to the Ras
      related GTP-binding protein superfamily and exhibits increased expression in
      various human cancers. We demonstrated that p53 increases the intracellular IP3
      and Ca2+ levels and decreases the LC3 protein levels through its target gene
      Rap2B, suggesting that p53 can inhibit the autophagic response triggered by
      starvation via upregulation of the Rap2B-PLCepsilon-IP3-Ca2+ pathway. As a
      confirmed target gene of p53, we believe that further investigating potential
      functions of Rap2B in autophagy and tumorigenesis will provide a novel strategy
      for cancer therapy.

PMID- 29029387
TI  - The beta-NAD+ salvage pathway and PKC-mediated signaling influence localized PARP
      1 activity and CTCF Poly(ADP)ribosylation.
AB  - Poly(ADP)ribosylation (PARylation) of the chromatin architectural protein CTCF is
      critical for CTCF-dependent regulation of chromatin boundary and insulator
      elements. Loss of CTCF PARylation results in epigenetic silencing of certain
      tumor suppressor genes through destabilization of nearby chromatin boundaries. We
      investigated the metabolic and mechanistic processes that regulate PARP-1
      mediated CTCF PARylation in human cancer cell lines and discovered a key role for
      the expression and activity of beta-NAD+ salvage enzymes, NAMPT and NMNAT-1.
      These enzymes are downregulated in cells that exhibit reduced CTCF PARylation,
      resulting in a decreased concentration of nuclear beta-NAD+. In these cells,
      decreased NMNAT-1 expression is enforced by a proteasome-mediated feedback loop
      resulting in degradation of NMNAT-1, transcriptional repression of NAMPT, and
      suppression of PARP-1 activity. Interestingly, dePARylated CTCF is associated in
      a stable protein complex with PARP-1 and NMNAT-1 in cancer cells harboring
      silenced tumor suppressor genes. Although the metabolic context in these cells
      favors suppression of PARP-1 activity, CTCF PARylation can be restored by Protein
      Kinase C (PKC) signaling. PKC induces dissociation of the catalytically inactive
      PARP-1/NMNAT-1/CTCF protein complex and phosphorylation of NMNAT-1, which
      stimulates its proteasome-mediated degradation. Our findings suggest that CTCF
      PARylation is underpinned by a cellular metabolic context engendered by
      regulation of the beta-NAD+ salvage pathway in which NMNAT-1 acts as a rheostat
      to control localized beta-NAD+ synthesis at CTCF/PARP-1 complexes.

PMID- 29029386
TI  - Exome sequencing analysis of murine medulloblastoma models identifies WDR11 as a
      potential tumor suppressor in Group 3 tumors.
AB  - Mouse models of human cancers are widely used in cancer research, yet questions
      frequently arise regarding their faithfulness in recapitulating their human
      counterparts. To compare the somatic mutations of murine models with human
      medulloblastoma (MB), we performed whole-exome sequencing on 12 tumors
      representing three distinct medulloblastoma subgroups: Wnt, Sonic Hedgehog (Shh)
      and Group 3 (G3). In total, 64 somatic mutations were identified and validated,
      including 40 predicted to cause amino acid changes. After filtering and cross
      species analysis with 366 human MBs from four independent studies, human
      orthologs for 16 of the 40 mouse genes were found to harbor non-silent mutations
      in human MB. Loss-of-function Kmt2d mutations detected in one mouse tumor was
      previously reported in 30 of 366 human MBs. In mice bearing G3 MB, one mouse
      succumbed to tumor burden at least 15 days earlier than other mice, raising the
      possibility that somatic mutations may have accelerated the tumorigenesis
      process. In this mouse tumor, four novel candidate genes harbored non-silent
      somatic mutations, Lrfn2, Smyd1, Ubn2 and Wdr11. Extended survival was found in
      mice harboring mouse G3 overexpressing WDR11 but not the other three genes. Genes
      in the KEGG WNT signaling pathway, including Ccnd1/2/3, Myc and Tcf7l1, were down
      regulated in the transcriptome of G3 MB tumorspheres overexpressing WDR11,
      consistent with reduced tumor progression. In conclusion, we demonstrated that
      common spontaneous mutations were shared between human and murine models of MB
      suggesting similar molecular mechanisms of tumorigenesis, and identified WDR11 as
      a protein with tumor suppressive activity in G3 MB.

PMID- 29029388
TI  - Rapamycin-induced miR-21 promotes mitochondrial homeostasis and adaptation in
      mTORC1 activated cells.
AB  - mTORC1 hyperactivation drives the multi-organ hamartomatous disease tuberous
      sclerosis complex (TSC). Rapamycin inhibits mTORC1, inducing partial tumor
      responses; however, the tumors regrow following treatment cessation. We
      discovered that the oncogenic miRNA, miR-21, is increased in Tsc2-deficient cells
      and, surprisingly, further increased by rapamycin. To determine the impact of miR
      21 in TSC, we inhibited miR-21 in vitro. miR-21 inhibition significantly
      repressed the tumorigenic potential of Tsc2-deficient cells and increased
      apoptosis sensitivity. Tsc2-deficient cells' clonogenic and anchorage independent
      growth were reduced by ~50% (p<0.01) and ~75% (p<0.0001), respectively, and
      combined rapamycin treatment decreased soft agar growth by ~90% (p<0.0001). miR
      21 inhibition also increased sensitivity to apoptosis. Through a network biology
      driven integration of RNAseq data, we discovered that miR-21 promotes
      mitochondrial adaptation and homeostasis in Tsc2-deficient cells. miR-21
      inhibition reduced mitochondrial polarization and function in Tsc2-deficient
      cells, with and without co-treatment with rapamycin. Importantly, miR-21
      inhibition limited Tsc2-deficient tumor growth in vivo, reducing tumor size by
      approximately 3-fold (p<0.0001). When combined with rapamcyin, miR-21 inhibition
      showed even more striking efficacy, both during treatment and after treatment
      cessation, with a 4-fold increase in median survival following rapamycin
      cessation (p=0.0008). We conclude that miR-21 promotes mTORC1-driven
      tumorigenesis via a mechanism that involves the mitochondria, and that miR-21 is
      a potential therapeutic target for TSC-associated hamartomas and other mTORC1
      driven tumors, with the potential for synergistic efficacy when combined with
      rapalogs.

PMID- 29029389
TI  - A ketogenic diet supplemented with medium-chain triglycerides enhances the anti
      tumor and anti-angiogenic efficacy of chemotherapy on neuroblastoma xenografts in
      a CD1-nu mouse model.
AB  - Neuroblastoma (NB) is a pediatric malignancy characterized by a marked reduction
      in aerobic energy metabolism. Recent preclinical data indicate that targeting
      this metabolic phenotype by a ketogenic diet (KD), especially in combination with
      calorie restriction, slows tumor growth and enhances metronomic cyclophosphamide
      (CP) therapy of NB xenografts. Because calorie restriction would be
      contraindicated in most cancer patients, the aim of the present study was to
      optimize the KD such that the tumors are sensitized to CP without the need of
      calorie restriction. In a NB xenograft model, metronomic CP was combined with KDs
      of different triglyceride compositions and fed to CD1-nu mice ad libitum.
      Metronomic CP in combination with a KD containing 8-carbon medium-chain
      triglycerides exerted a robust anti-tumor effect, suppressing growth and causing
      a significant reduction of tumor blood-vessel density and intratumoral
      hemorrhage, accompanied by activation of AMP-activated protein kinase in NB
      cells. Furthermore, the KDs caused a significant reduction in the serum levels of
      essential amino acids, but increased those of serine, glutamine and glycine. Our
      data suggest that targeting energy metabolism by a modified KD may be considered
      as part of a multimodal treatment regimen to improve the efficacy of classic anti
      NB therapy.

PMID- 29029385
TI  - Analyses of germline variants associated with ovarian cancer survival identify
      functional candidates at the 1q22 and 19p12 outcome loci.
AB  - We previously identified associations with ovarian cancer outcome at five genetic
      loci. To identify putatively causal genetic variants and target genes, we
      prioritized two ovarian outcome loci (1q22 and 19p12) for further study.
      Bioinformatic and functional genetic analyses indicated that MEF2D and ZNF100 are
      targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12,
      the chromatin interaction of a putative regulatory element with the ZNF100
      promoter region correlated with candidate outcome variants. At 1q22, putative
      regulatory elements enhanced MEF2D promoter activity and haplotypes containing
      candidate outcome variants modulated these effects. In a public dataset, MEF2D
      and ZNF100 expression were both associated with ovarian cancer progression-free
      or overall survival time. In an extended set of 6,162 epithelial ovarian cancer
      patients, we found that functional candidates at the 1q22 and 19p12 loci, as well
      as other regional variants, were nominally associated with patient outcome;
      however, no associations reached our threshold for statistical significance
      (p<1*10-5). Larger patient numbers will be needed to convincingly identify any
      true associations at these loci.

PMID- 29029391
TI  - Ginsenoside Rg3 inhibits the senescence of prostate stromal cells through down
      regulation of interleukin 8 expression.
AB  - Senescent stromal cells support the development of prostate cancer and are
      considered potential therapeutic targets. This research evaluated the regulatory
      effects of ginsenoside Rg3 on the senescence of prostatic stromal cells pre
      incubated in medium supplemented with 0.5% fetal bovine serum. The results
      revealed that ginsenoside Rg3 decreased the number of stromal cells positively
      stained with a senescent cell marker (senescence-associated beta-galactosidase).
      Ginsenoside Rg3 also increased the viability of stromal cells and promoted cell
      cycle transition from G0/G1 to S phase, as well as inhibited the carcinoma
      associated fibroblast-like phenotype in prostate stromal cells, through the up
      regulation of smooth muscle cell markers SM22 and smooth muscle myosin heavy
      chain. Conditioned medium collected from stromal cells treated with ginsenoside
      Rg3 exhibited an attenuated effect on the promotion of prostate cancer cell
      migration compared with conditioned medium from stromal cells without Rg3
      treatment. Down-regulation of interleukin 8 (IL-8) in a dose- and time-dependent
      manner was observed in ginsenoside Rg3-treated stromal cells, and over-expression
      or addition of IL-8 reversed the anti-senescence role of Rg3 in prostate stromal
      cells. Furthermore, ginsenoside Rg3 down-regulated IL-8 expression by decreasing
      the reactive oxygen species level in prostatic stromal cells and reducing the
      transcriptional activity of IL-8 promoter by damping the transcription factors
      C/EBP beta and p65 binding to IL-8 promoter. Our research revealed that
      ginsenoside Rg3 was able to inhibit prostate stromal cell senescence by down
      regulating IL-8 expression. The results suggest a potential value for ginsenoside
      Rg3 in prostate cancer treatment through the targeting of pro-carcinogenic
      senescent stromal cells.

PMID- 29029392
TI  - Spermine and spermidine reversed age-related cardiac deterioration in rats.
AB  - Aging is the most important risk factor for cardiovascular disease (CVD). Slowing
      or reversing the physiological impact of heart aging may reduce morbidity and
      mortality associated with age-related CVD. The polyamines, spermine (SP) and
      spermidine (SPD) are essential for cell growth, differentiation and apoptosis,
      and levels of both decline with age. To explore the effects of these polyamines
      on heart aging, we administered SP or SPD intraperitoneally to 22- to 24-month
      old rats for 6 weeks. Both treatments reversed and inhibited age-related
      myocardial morphology alterations, myocardial fibrosis, and cell apoptosis. Using
      combined proteomics and metabolomics analyses, we identified proteins and
      metabolites up- or downregulated by SP and SPD in aging rat hearts. SP
      upregulated 51 proteins and 28 metabolites while downregulating 80 proteins and
      29 metabolites. SPD upregulated 44 proteins and 24 metabolites and downregulated
      84 proteins and 176 metabolites. These molecules were mainly associated with
      immune responses, blood coagulation, lipid metabolism, and glutathione metabolism
      pathways. Our study provides novel molecular information on the cardioprotective
      effects of polyamines in the aging heart, and supports the notion that SP and SPD
      are potential clinical therapeutics targeting heart disease.

PMID- 29029394
TI  - Long non-coding RNA H19 induces hippocampal neuronal apoptosis via Wnt signaling
      in a streptozotocin-induced rat model of diabetes mellitus.
AB  - Defects in hippocampal synaptic plasticity and disorders of memory and learning
      are the central nervous system complications of diabetes mellitus (DM). Here, we
      used a streptozotocin-induced rat DM model to investigate the effects of long non
      coding RNA H19 (lncRNA H19) on learning and memory and apoptosis of hippocampal
      neurons, and the involvement of the Wnt signaling. Our data demonstrate that
      lncRNA H19 is highly expressed in rats with DM. Over-expression of lncRNA H19
      increased positioning navigation latency in DM rats and decreased duration of
      space exploration. lncRNA H19 over-expression also increased hippocampal neuronal
      apoptosis and expression of Wnt3, beta-catenin, TCF-1, Bax, caspase-8 and caspase
      3. By contrast, expression of GSK-3beta and Bcl-2 was suppressed in DM rats over
      expressing lncRNA H19. These results suggest that lncRNA H19 induces hippocampal
      neuronal apoptosis via Wnt signaling, and that inhibition of lncRNA H19 may serve
      as a promising novel target for the treatment of cognitive decline in patients
      with DM.

PMID- 29029393
TI  - Intermittent treatment with farnesyltransferase inhibitor and sulforaphane
      improves cellular homeostasis in Hutchinson-Gilford progeria fibroblasts.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic condition
      associated with mutations in the LMNA gene. This disease recapitulates some
      aspects of normal aging, such as hair loss, thin skin, joint stiffness, and
      atherosclerosis. The latter leads to heart attack or stroke that causes death at
      an average age of 14.6 years in children with HGPS. The typical LMNA mutation
      results in the production of a truncated prelamin A protein, progerin, that
      remains permanently farnesylated and abnormally associated with the nuclear
      envelope. Farnesyltransferase inhibitors (FTIs) reverse nuclear structure
      abnormalities that are characteristic of HGPS cells. The first clinical trial
      using the FTI, Ionafarnib, demonstrated some improvements in HGPS children and,
      in particular, showed a decrease in arterial stiffness. Recently, we reported
      that sulforaphane, an antioxidant derived from cruciferous vegetables,
      efficiently stimulates autophagy and enhances progerin clearance in HGPS
      fibroblasts. In the present study, we investigated the effect of combined
      lonafarnib and sulforaphane treartment in HGPS fibroblast cultures. We report
      that co-administration of both drugs exerts a synergistic and additive positive
      effect on autophagy activity but was cytotoxic to HGPS cells. In contrast,
      intermittent treatment with lonafarnib followed by sulforaphane separately and in
      repeated cycles rescued the HGPS cellular phenotype. We propose that intermittent
      treatment with FTI and SFN separately might be a promising therapeutic avenue for
      children with HGPS.

PMID- 29029395
TI  - RASAL1 is a potent regulator of hepatic stellate cell activity and liver
      fibrosis.
AB  - Liver fibrosis, leading to cirrhosis and liver failure, can occur after chronic
      liver injury. The transition of hepatic stellate cells (HSCs) from quiescent
      cells into proliferative and fibrogenic cells is a central event in liver
      fibrosis. Here, we show that RAS protein activator like-1 (RASAL1), a RAS-GTPase
      activating protein, which switches off RAS activity, is significantly decreased
      during HSC activation, and that HSC activation can be antagonized by forced
      expression of the RASAL1 protein. We demonstrate that RASAL1 suppresses HSC
      proliferation by regulating the Ras-MAPK pathway, and that RASAL1 suppresses HSC
      fibrogenic activity by regulating the PKA-LKB1-AMPK-SRF pathway by interacting
      with angiotensin II receptor, type 1. We also show that RASAL1-deficient mice are
      more susceptible to liver fibrosis. These data demonstrate that deregulated
      RASAL1 expression levels and the affected downstream intracellular signaling are
      central mediators of perpetuated HSC activation and fibrogenesis in the liver.

PMID- 29029390
TI  - Extracellular truncated tau causes early presynaptic dysfunction associated with
      Alzheimer's disease and other tauopathies.
AB  - The largest part of tau secreted from AD nerve terminals and released in cerebral
      spinal fluid (CSF) is C-terminally truncated, soluble and unaggregated supporting
      potential extracellular role(s) of NH2 -derived fragments of protein on synaptic
      dysfunction underlying neurodegenerative tauopathies, including Alzheimer's
      disease (AD). Here we show that sub-toxic doses of extracellular-applied human
      NH2 tau 26-44 (aka NH 2 htau) -which is the minimal active moiety of neurotoxic
      20-22kDa peptide accumulating in vivo at AD synapses and secreted into parenchyma
      acutely provokes presynaptic deficit in K+ -evoked glutamate release on
      hippocampal synaptosomes along with alteration in local Ca2+ dynamics. Neuritic
      dystrophy, microtubules breakdown, deregulation in presynaptic proteins and loss
      of mitochondria located at nerve endings are detected in hippocampal cultures
      only after prolonged exposure to NH 2 htau. The specificity of these biological
      effects is supported by the lack of any significant change, either on neuronal
      activity or on cellular integrity, shown by administration of its reverse
      sequence counterpart which behaves as an inactive control, likely due to a poor
      conformational flexibility which makes it unable to dynamically perturb
      biomembrane-like environments. Our results demonstrate that one of the AD
      relevant, soluble and secreted N-terminally truncated tau forms can early
      contribute to pathology outside of neurons causing alterations in synaptic
      activity at presynaptic level, independently of overt neurodegeneration.

PMID- 29029396
TI  - Activation of cannabinoid receptor type II by AM1241 protects adipose-derived
      mesenchymal stem cells from oxidative damage and enhances their therapeutic
      efficacy in myocardial infarction mice via Stat3 activation.
AB  - The poor survival of cells in ischemic sites diminishes the therapeutic efficacy
      of stem cell therapy. Previously we and others have reported that Cannabinoid
      receptor type II (CB2) is protective during heart ischemic injury for its anti
      oxidative activity. However, whether CB2 activation could improve the survival
      and therapeutic efficacy of stem cells in ischemic myocardium and the underlying
      mechanisms remain elusive. Here, we showed evidence that CB2 agonist AM1241
      treatment could improve the functional survival of adipose-derived mesenchymal
      stem cells (AD-MSCs) in vitro as well as in vivo. Moreover, AD-MSCs adjuvant with
      AM1241 improved cardiac function, and inhibited cardiac oxidative stress,
      apoptosis and fibrosis. To unveil possible mechanisms, AD-MSCs were exposed to
      hydrogen peroxide/serum deprivation to simulate the ischemic environment in
      myocardium. Results delineated that AM1241 blocked the apoptosis, oxidative
      damage and promoted the paracrine effects of AD-MSCs. Mechanistically, AM1241
      activated signal transducers and activators of transcription 3 (Stat3) through
      the phosphorylation of Akt and ERK1/2. Moreover, the administration of AM630,
      LY294002, U0126 and AG490 (inhibitors for CB2, Akt, ERK1/2 and Stat3,
      respectively) could abolish the beneficial actions of AM1241. Our result support
      the promise of CB2 activation as an effective strategy to optimize stem cell
      based therapy possibly through Stat3 activation.

PMID- 29029397
TI  - Tsp1 promotes alveolar stem cell proliferation and its down-regulation relates to
      lung inflammation in intralobar pulmonary sequestration.
AB  - An aberrant systemic artery supply results in recurrent infections in the
      abnormal lung lobe of intralobar pulmonary sequestration (ILS). The mechanisms
      underlying such persistent inflammation are unknown. Here, we hypothesize that
      alteration of an endothelial cell niche for alveolar epithelial cells results in
      the impaired proliferation potential of alveolar progenitor cells, leading to the
      defective defense mechanism in intralobar pulmonary sequestration. Paraffin
      sections of lung tissues from patients with intralobar pulmonary sequestration or
      from healthy controls were collected for analysis of alveolar epithelial
      alterations in intralobar pulmonary sequestration by quantitative RT-PCR or
      immunofluorescent staining. Differential transcripts were identified between
      human pulmonary artery endothelial cells and human aortic endothelial cells by
      microarray. Validation of microarray data by quantitative PCR analysis indicated
      that thrombospondin-1 expression level is low in near-lesion part but high in
      lesion part of ILS lobe as compared to healthy controls. In vitro 3-D matrigel
      culture was adopted to evaluate the regulation of alveolar progenitor cells by
      thrombospondin-1 and CD36. We found that the proliferative potential of alveolar
      type 2 stem/progenitor cells was impaired in intralobar pulmonary sequestration.
      Mechanistically, we discovered that endothelial thrombospondin-1 promotes
      alveolar type 2 cell proliferation through the interaction with CD36. These data
      demonstrate that alveolar stem cells are impaired in the abnormal lobe from
      patients with intralobar pulmonary sequestration and imply that restoring
      epithelial integrity can be beneficial for the future treatments of recurrent
      infections in lung pathologies.

PMID- 29029398
TI  - Dietary ZnO nanoparticles alters intestinal microbiota and inflammation response
      in weaned piglets.
AB  - The present study was carried out to determine whether low dose of zinc oxide
      nanoparticles (Nano-ZnO) could serve as a potential substitute of pharmacological
      dose of traditional ZnO in weaned piglets. 180 crossbred weaning piglets were
      randomly assigned to 3 treatments. Experimental animals were fed basal diet
      supplemented with 0 mg Zn/kg (Control), 600 mg Zn/kg (Nano-ZnO) and 2000 mg Zn/kg
      (ZnO) for 14 days. On day 14 after weaning, the piglets fed Nano-ZnO did not
      differ from those fed traditional ZnO in growth performance and jejunal
      morphology, while Nano-ZnO treatment could significantly alleviate the incidence
      of diarrhea (P < 0.05). In jejunum, the mRNA expressions of intestinal
      antioxidant enzymes and tight junction proteins were increased (P < 0.05) in Nano
      ZnO treatment. In ileum, the expression levels of IFN-gamma, IL-1beta, TNF-alpha
      and NF-kappaB were decreased (P < 0.05). Gene sequencing analysis of 16S rRNA
      revealed that dietary Nano-ZnO increased the bacterial richness and diversity in
      ileum, while decreased both of them in cecum and colon. Specifically, the
      relative abundances of Streptococcus in ileum, Lactobacillus in colon were
      increased, while the relative abundances of Lactobacillus in ileum, Oscillospira
      and Prevotella in colon were decreased (P < 0.05). In conclusion, our data reveal
      that low dose of Nano-ZnO (600 mg Zn/kg) can effectively reduce piglet diarrhea
      incidence, similar to high dose of traditional ZnO (2000 mg Zn/kg), which may be
      mediated by improving intestinal microbiota and inflammation response in piglets,
      and help to reduce zinc environmental pollution.

PMID- 29029399
TI  - A cellular platform for the evaluation of immune checkpoint molecules.
AB  - Blockade of the T cell coinhibitory molecules CTLA-4 and PD-1 has clinical
      utility to strengthen T cell responses. In addition to these immune checkpoints
      an ever-growing number of molecules has been implicated in generating
      coinhibitory signals in T cells. However, investigating coinhibitory molecules in
      primary human cells is complicated by the restricted expression and promiscuity
      of both coinhibitory receptors and their ligands. Here we have evaluated the
      potential of fluorescence-based transcriptional reporters based on the human
      Jurkat T cell line in conjunction with engineered T cell stimulator cell lines
      for investigating coinhibitory pathways. CTLA-4, PD-1, TIGIT, BTLA and 2B4
      expressing reporter cells were generated and activated with T cell stimulator
      cells expressing cognate ligands of these molecules. All accessory molecules
      tested were functional in our reporter system. Engagement of CTLA-4, PD-1, BTLA
      and TIGIT by their ligands significantly inhibited T cell activation, whereas
      binding of 2B4 by CD48 resulted in enhanced responses. Mutational analysis
      revealed intracellular motifs that are responsible for BTLA mediated T cell
      inhibition and demonstrates potent reporter inhibition by CTLA-4 independent of
      cytoplasmic signaling motifs. Moreover, considerably higher IC50 values were
      measured for the CTLA-4 blocker Ipilimumab compared to the PD-1 antibody
      Nivolumab. Our findings show that coinhibitory pathways can be evaluated in
      Jurkat-based transcriptional reporters and yield novel insights on their
      function. Results obtained from this robust reductionist system can complement
      more time consuming and complex studies of such pathways in primary T cells.

PMID- 29029400
TI  - Rat embryonic fibroblasts immortalized by MRPS18-2 protein are target for NK
      cells.
AB  - Overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2) led
      to immortalization of primary rat embryonic fibroblasts (REFs). The derived cells
      (18IM) expressed embryonic stem cell markers. Noteworthy, genes encoding the COX
      family proteins were up-regulated significantly. It is known that the COX family
      proteins are involved in the regulation of immune response. In the present work
      we demonstrate that 18IM cells behave like stem cells when subjected to directed
      differentiation in vitro. However, unlike stem cells, 18IM cells do not develop
      tumors in vivo, in SCID mice. This phenomenon is observed due to the strong
      natural killer (NK) cell immunogenicity. 18IM cells were better recognized by NK
      cells, compared with primary REFs, as was shown by a standard NK killing assay.
      Our data explain asymmetry in behavior of stem-like cells in vivo and in vitro,
      and this support the notion that stem and/or cancer-initiating cells are
      preferred targets for NK-cells. Concluding, the S18-2 protein is a putative
      target for cancer vaccines.

PMID- 29029401
TI  - Lysine methylation of FEN1 by SET7 is essential for its cellular response to
      replicative stress.
AB  - The DNA damage response (DDR) is central to the cell survival and it requires
      post-translational modifications, in part, to sense the damage, amplify the
      signaling response and recruit and regulate DNA repair enzymes. Lysine
      methylation of histones such as H4K20 and non-histone proteins including p53 has
      been shown to be essential for the mounting of the DDR. It is well-known that the
      lysine methyltransferase SET7 regulates the DDR, as cells lacking this enzyme are
      hypersensitive to chemotherapeutic drugs. To define addition substrates of SET7
      involved in the DDR, we screened a peptide array encompassing potential lysine
      methylation sites from >100 key DDR proteins and identified peptides from 58
      proteins to be lysine methylated defining a methylation consensus sequence of
      [S>K-2; S>R-1; K0] consistent with previous findings. We focused on K377
      methylation of the Flap endonuclease 1 (FEN1), a structure specific endonuclease
      with important functions in Okazaki fragment processing during DNA replication as
      a substrate of SET7. FEN1 was monomethylated by SET7 in vivo in a cell cycle
      dependent manner with levels increasing as cells progressed through S phase and
      decreasing as they exited S phase, as detected using K377me1 specific antibodies.
      Although K377me1 did not affect the enzymatic activity of FEN1, it was required
      for the cellular response to replicative stress by FEN1. These finding define
      FEN1 as a new substrate of SET7 required for the DDR.

PMID- 29029403
TI  - Marital status and survival in patients with primary liver cancer.
AB  - BACKGROUND: Marital status is viewed as an independent prognostic factor for
      survival in various cancer types. However, its role in primary liver cancer has
      yet to be thoroughly explored. OBJECTIVE: To investigate the impact of marital
      status on survival outcomes among liver cancer patients. RESULTS: We finally
      identified 40,809 eligible liver cancer patients between 2004 and 2012, including
      21,939 (53.8%) patients were married at diagnosis and 18,870 (46.2%) were
      unmarried (including 5,871 divorced/separated, 4,338 widowed and 8,660 single).
      Married patients enjoyed overall and cause-specific survival outcomes compared
      with patients who were divorced/separated, widowed, single, respectively. The
      survival benefit associated with marriage still persisted even after adjusted for
      known confounders. Widowed individuals were at greater risk of overall and cancer
      specific mortality compared to other groups. Similar associations were observed
      in subgroup analyses according to SEER stage. MATERIALS AND METHODS: We used the
      Surveillance, Epidemiology and End Results (SEER) database to identify 40,809
      patients diagnosed with primary liver cancer between 2004 and 2012. Kaplan-Meier
      analysis and Cox regression were performed to identify the influence of marital
      status on overall survival (OS) and liver cancer-specific survival (CSS).
      CONCLUSIONS: In primary liver cancer patients, married patients enjoyed survival
      benefits while widowed persons suffered survival disadvantages in both overall
      survival and cancer-specific survival.

PMID- 29029402
TI  - Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells.
AB  - Glioblastoma (GBM) stem cells (GSCs) reside in both hypoxic and vascular
      microenvironments within tumors. The molecular mechanisms that allow GSCs to
      occupy such contrasting niches are not understood. We used patient-derived GBM
      cultures to identify GSC subtypes with differential activation of Notch
      signaling, which co-exist in tumors but occupy distinct niches and match their
      metabolism accordingly. Multipotent GSCs with Notch pathway activation reside in
      perivascular niches, and are unable to entrain anaerobic glycolysis during
      hypoxia. In contrast, most CD133-expressing GSCs do not depend on canonical Notch
      signaling, populate tumors regardless of local vascularity and selectively
      utilize anaerobic glycolysis to expand in hypoxia. Ectopic activation of Notch
      signaling in CD133-expressing GSCs is sufficient to suppress anaerobic glycolysis
      and resistance to hypoxia. These findings demonstrate a novel role for Notch
      signaling in regulating GSC metabolism and suggest intratumoral GSC heterogeneity
      ensures metabolic adaptations to support tumor growth in diverse tumor
      microenvironments.

PMID- 29029404
TI  - Quercetin induced ROS production triggers mitochondrial cell death of human
      embryonic stem cells.
AB  - Small molecules to selectively induce cell death of undifferentiated human
      pluripotent stem cells (hPSCs) have been developed with the aim of lowering the
      risk of teratoma formation during hPSC-based cell therapy. In this context, we
      have reported that Quercetin (QC) induces cell death selectively in hESCs via p53
      mitochondrial localization. However, the detailed molecular mechanism by which
      hESCs undergo selective cell death induced by QC remains unclear. Herein, we
      demonstrate that mitochondrial reactive oxygen species (ROS), strongly induced by
      QC in human embryonic stem cells (hESCs) but not in human dermal fibroblasts
      (hDFs), were responsible for QC-mediated hESC's cell death. Increased p53 protein
      stability and subsequent mitochondrial localization by QC treatment triggered
      mitochondrial cell death only in hESCs. Of interest, peptidylprolyl isomerase D
      [PPID, also called cyclophilin D (CypD)], which functions in mitochondrial
      permeability transition and mitochondrial cell death, was highly expressed in
      hESCs. Inhibition of CypD by cyclosporine A (CsA) clearly inhibited the QC
      mediated loss of mitochondrial membrane potential and mitochondrial cell death.
      These results suggest that p53 and CypD in the mitochondria are critical for the
      QC-mediated induction of cell death in hESCs.

PMID- 29029405
TI  - SOX7 promotes the maintenance and proliferation of B cell precursor acute
      lymphoblastic cells.
AB  - B cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most frequent type
      of cancer in children. Despite progresses in curative treatment, intensive
      chemotherapy regimens still cause life threatening complications. A better
      understanding of the molecular mechanisms underlying the emergence and
      maintenance of BCP-ALL is fundamental for the development of novel therapies.
      Here, we establish that SOX7 is frequently and specifically expressed in BCP-ALL
      and that the expression of this transcription factor does not correlate with any
      specific cytogenetic abnormalities. Using human leukemia model systems, we
      establish that the down-regulation of SOX7 in BCP-ALL causes a significant
      decrease in proliferation and clonogenicity in vitro that correlates with a delay
      in leukemia initiation and burden in vivo. Overall, these results identify a
      novel and important functional role for the transcription factor SOX7 in
      promoting the maintenance of BCP-ALL.

PMID- 29029406
TI  - Lyn mediates FIP1L1-PDGFRA signal pathway facilitating IL-5RA intracellular
      signal through FIP1L1-PDGFRA/JAK2/Lyn/Akt network complex in CEL.
AB  - The Fip1-like1 (FIP1L1)-platelet-derived growth factor receptor alpha (PDGFRA)
      (F/P) oncogene can cause chronic eosinophilic leukemia (CEL), but requires IL-5
      cytokine participation. In this study, we investigate the mechanism of F/P in
      collaboration with IL-5 in CEL. The results showed that Lyn, a key effector in
      the IL-5-motivated eosinophil production, is extensively activated in F/P
      positive CEL cells. Lyn can associate and phosphorylate IL-5 receptor alpha (IL
      5RA) in F/P-positive cells. Moreover, the activation of Lyn and IL-5R kinase were
      strengthened when the cells were stimulated by IL-5. Lyn inhibition in F/P
      positive CEL cells attenuated cellular proliferation, induced apoptosis, and
      blocked cell migration and major basic protein (MBP) release. We identified the
      FIP1L1-PDGFRA/JAK2/Lyn/Akt complex in the F/P-expressing cells which can be
      disrupted by dual inhibition of JAK2 and Lyn, repressing cell proliferation in
      both EOL-1(F/P-positive human eosinophilic cell line) and imatinib-resistance
      (IR) cells. Altogether, our data demonstrate that Lyn is a vital downstream
      kinase activated by F/P converged with IL-5 signals in CEL cells. Lyn activate
      and expand IL-5RA intracellular signaling through FIP1L1-PDGFRA/JAK2/Lyn/Akt
      network complex, provoking eosinophils proliferation and exaggerated activation
      manifested as CEL.

PMID- 29029407
TI  - Molecular profiling of colorectal pulmonary metastases and primary tumours:
      implications for targeted treatment.
AB  - This study aimed to molecularly characterise colorectal pulmonary metastases (PM)
      and investigate whether their molecular profiles were concordant with those of
      the primary tumour. Clinical data and archival formalin fixed paraffin embedded
      tissue samples were retrospectively collected from patients who underwent >= 1
      pulmonary metastasectomies for colorectal cancer between 1997-2012. Primary
      tumour and metastatic samples were analysed using a targeted capture sequencing
      panel of 46 cancer-associated genes. The 5-year progression-free and overall
      survival rates for the 81 patients in this study were 32% (95% CI 22-42%) and 77%
      (95% CI 66-85%) respectively. Fifty-four patients had samples available from >= 1
      PM, and sequencing data were successfully obtained from 33 PM from 24 patients.
      The most frequently mutated genes were APC (71%), KRAS (58%) and TP53 (46%).
      Seventy-three percent of the 15 patients with matched primary and PM samples and
      6 of the 7 patients (86%) with data from >= 2 PM had concordant molecular
      profiles. The concordance for KRAS and NRAS was 100%. At our institutions,
      patients with resectable colorectal PM had a favourable prognosis. RAS mutations
      were commonly detected in PM and the molecular profiles of colorectal PM were
      highly concordant with the primary tumour.

PMID- 29029408
TI  - RNAi targeting Nogo Receptor enhanced survival and proliferation of murine
      retinal ganglion cells during N-methyl-D-aspartate-induced optic nerve crush.
AB  - We investigated the effects of lentivirus-mediated RNAi targeting of Nogo
      Receptor (NgR) on the proliferation and survival of murine retinal ganglion cells
      (mRGCs) in vitro and in vivo. Cultured mRGCs and C57BL/6 male mice were divided
      into 4 experimental groups: blank, model [100 MUM N-methyl-D-aspartate (NMDA)],
      nscRNA (100 MUM NMDA+ nscRNA vectors) and siNgR (100 MUM NMDA+ siNgR vectors).
      CCK-8 and flow cytometry analyses revealed that silencing NgR enhanced
      proliferation, cell cycling and survival of NMDA-treated mRGCs. H&E staining
      showed that NgR silencing enhanced mRGC cell density and reduced angiogenesis in
      NMDA-treated retinal tissues. TUNEL assays showed that mRGC apoptosis was
      significantly diminished by NgR silencing in NMDA-treated retinal tissues.
      Western blotting and qRT-PCR analysis in NMDA-treated mRGCs and murine retinal
      tissues revealed that NgR silencing resulted in downregulation of RhoA signaling
      (RhoA and ROCK2). Western blotting showed that levels of activated Bax and
      cleaved caspase 3 were decreased, while Bcl-2 and pro-caspase 3 were increased in
      NMDA-treated mRGCs and murine retinal tissues, which corroborated the decreased
      apoptosis. These findings indicate that NgR gene silencing increases
      proliferation and survival of mRGCs in NMDA-treated murine retinas, which
      suggests a potential for therapeutic application to preventing optic nerve
      damage.

PMID- 29029409
TI  - Metabolic characterization and pathway analysis of berberine protects against
      prostate cancer.
AB  - Recent explosion of biological data brings a great challenge for the traditional
      methods. With increasing scale of large data sets, much advanced tools are
      required for the depth interpretation problems. As a rapid-developing technology,
      metabolomics can provide a useful method to discover the pathogenesis of
      diseases. This study was explored the dynamic changes of metabolic profiling in
      cells model and Balb/C nude-mouse model of prostate cancer, to clarify the
      therapeutic mechanism of berberine, as a case study. Here, we report the findings
      of comprehensive metabolomic investigation of berberine on prostate cancer by
      high-throughput ultra performance liquid chromatography-mass spectrometry coupled
      with pattern recognition methods and network pathway analysis. A total of 30
      metabolite biomarkers in blood and 14 metabolites in prostate cancer cell were
      found from large-scale biological data sets (serum and cell metabolome),
      respectively. We have constructed a comprehensive metabolic characterization
      network of berberine to protect against prostate cancer. Furthermore, the results
      showed that berberine could provide satisfactory effects on prostate cancer via
      regulating the perturbed pathway. Overall, these findings illustrated the power
      of the ultra performance liquid chromatography-mass spectrometry with the pattern
      recognition analysis for large-scale biological data sets may be promising to
      yield a valuable tool that insight into the drug action mechanisms and drug
      discovery as well as help guide testable predictions.

PMID- 29029410
TI  - Efficient intracellular delivery makes cancer cells sensitive to nanoemulsive
      chemodrugs.
AB  - Evodiamine has been documented to possess activities in numerous cancer cells.
      Our preliminary study showed that A549 cells were insensitive to evodiamine. In
      this paper, A549 cells are sensitive to nanoemulsive evodiamine (EVONE) through
      an efficient intracellular and systematic delivery. EVONE entered tumor cells by
      energy-dependent and mainly through clathrin-mediated endocytosis. EVONE exerted
      a higher cytotoxicity in a dose- and time-dependent manner. The enhanced
      induction of cell cycle arrest was ascribed to the down-regulation of cyclin B
      and cyclin dependent kinase 1, while the enhanced induction of apoptosis was due
      to the activation of caspase -3, -8 and -9 and the decreased B-cell lymphoma 2/
      assaciated X protein ratio. Furthermore, the in vivo kinetic, bioavailability and
      in situ absorption characteristics of EVONE were much better than those of free
      evodiamine. The cancer cells insensitive to free chemodrugs became sensitive to
      nanoemulsive chemodrugs.

PMID- 29029411
TI  - Nestin expression involves invasiveness of esophageal carcinoma and its
      downregulation enhances paclitaxel sensitivity to esophageal carcinoma cell
      apoptosis.
AB  - Paclitaxel has been generally used to treat primary and metastatic esophageal
      carcinoma. It has been shown that nestin is highly expressed in esophageal
      carcinoma and that there is a strong association of nestin expression with poor
      prognosis in esophageal carcinoma patients. In this study, using
      immunohistochemistry, in situ hybridization and Western blotting we demonstrated
      that nestin was overexpressed in the invasive esophageal carcinoma. To further
      elucidate whether nestin inhibition could enhance paclitaxel sensitivity to
      esophageal carcinoma cells, we applied nestin siRNA in esophageal squamous cell
      carcinoma Eca-109 cells. Flow cytometry and TUNEL staining both showed that
      combination of paclitaxel treatment and nestin knockdown resulted in greater
      induction of apoptosis of esophageal carcinoma cells as compared with the cells
      transfected with control siRNA (also treated with paclitaxel). This study
      indicates that nestin knockdown enhances chemotherapeutic sensitivity of
      paclitaxel to esophageal carcinoma, and suggests that silencing of nestin could
      be a valuble therapeutic approach for enhancing drug sensitivity and thereby
      improving the treatment outcome of esophageal carcinoma patients.

PMID- 29029412
TI  - The value of phosphohistone H3 as a proliferation marker for evaluating invasive
      breast cancers: A comparative study with Ki67.
AB  - BACKGROUND: Established measurements of proliferation in breast cancer are Ki67
      and mitotic-activity-index (MAI), with problems in reproducibility and prognostic
      accuracy. Phosphohistone H3 (PHH3), a relatively novel IHC marker is specific for
      mitosis with good reproducibility. We hypothesized that PHH3 would be more
      reproducible and better represent proliferation than Ki67. RESULTS: PHH3
      identified easily-missed mitosis by MAI, as demonstrated by upgrading M grade at
      diagnosis (n = 29/218, evenly distributed). PHH3 accurately found hot-spots,
      supported by mitotic count agreement between low-power and 10HPFs (R2 = 0.999; P
      = 0.001). PHH3 was more reproducible than Ki67, measured by five-rater inter
      class correlation coefficient (0.904 > 0.712; P = 0.008). Finally, despite a
      relatively short follow-up (median 46 months; 7 recurrences) PHH3 was the only
      variable correlated with disease-free survival (P = 0.043), while all other
      conventional clinicopathologic variables, including Ki67 (P = 0.356), did not.
      MATERIALS AND METHODS: We compared Ki67 and PHH3 for 218 breast cancer surgical
      cases diagnosed from 2012 to 2013 at Severance hospital. The most representative
      invasive breast cancer surgical slides were immunohistochemically stained for
      Ki67 and PHH3. CONCLUSIONS: Poor reproducibility and inadequate representation of
      proliferation of Ki67 and MAI may be improved by PHH3, allowing better accuracy
      in breast cancer diagnostics.

PMID- 29029413
TI  - Targeting SHP-1-STAT3 signaling: A promising therapeutic approach for the
      treatment of cholangiocarcinoma.
AB  - Sorafenib is a multiple kinase inhibitor which targets Raf kinases, VEGFR, and
      PDGFR and is approved for the treatment of hepatocellular carcinoma (HCC).
      Previously, we found that p-STAT3 is a major target of SC-43, a sorafenib
      derivative. In this study, we report that SC-43-induced apoptosis in
      cholangiocarcinoma (CCA) via a novel mechanism. Three CCA cell lines (HuCCT-1,
      KKU-100 and CGCCA) were treated with SC-43 to determine their sensitivity to SC
      43-induced cell death and apoptosis. We found that SC-43 activated SH2 domain
      containing phosphatase 1 (SHP-1) activity, leading to p-STAT3 and downstream
      cyclin B1 and Cdc2 downregulation, which induced G2-M arrest and apoptotic cell
      death. Importantly, SC-43 augmented SHP-1 activity by direct binding to N-SH2 and
      relief of its autoinhibition. Deletion of the N-SH2 domain (dN1) or point
      mutation (D61A) of SHP-1 counteracted the effect of SC-43-induced SHP-1
      phosphatase activation and antiproliferation ability in CCA cells. In vivo assay
      revealed that SC-43 exhibited xenograft tumor growth inhibition, p-STAT3
      reduction and SHP-1 activity elevation. In conclusion, SC-43 induced apoptosis in
      CCA cells through the SHP-1/STAT3 signaling pathway.

PMID- 29029415
TI  - Oxymatrine suppresses the growth and invasion of MG63 cells by up-regulating PTEN
      and promoting its nuclear translocation.
AB  - Studies demonstrated that reduced PTEN levels are associated with poor prognoses
      of osteosarcoma. The nuclear localization of PTEN is important for its tumor
      suppressive function. Equally importantly, PTEN is the most significant negative
      regulator of PI3K/Akt signaling cascade, the constitutively activated pathway in
      osteosarcoma. In our study MG63 cells and U2OS cells were treated with the
      indicated concentrations of oxymatrine, in order to find the inhibition of
      oxymatrine to cells. We found the functions of oxymatrine on proliferation,
      apoptosis and invasion in cells. Oxymatrine could increase the expression of PTEN
      and promote its nuclear translocation in MG63 cells. In addition, oxymatrine
      could induce cell cycle arrest in G1 phase and apoptosis of MG63 cells. The
      migration and invasion potential of MG63 cells were also markedly inhibited by
      oxymatrine. Oxymatrine could suppress the growth and invasion of MG63 human
      osteosarcoma cells by up-regulating PTEN and promoting its nuclear translocation
      and inhibiting PI3K/Akt signaling pathway.

PMID- 29029414
TI  - Targeting ADAM17 inhibits human colorectal adenocarcinoma progression and tumor
      initiating cell frequency.
AB  - ADAM17 (a disintegrin and metalloproteinase 17)/TACE (TNFalpha converting enzyme)
      has emerged as a potential therapeutic target in colorectal cancer (CRC) and
      other cancers, due in part to its role in regulating various tumor cell surface
      proteins and growth factors and cytokines in the tumor microenvironment. The
      emergence of MEDI3622, a highly potent and specific antibody-based ADAM17
      inhibitor, has allowed testing of the concept that targeting ADAM17 may be an
      important new therapeutic approach for CRC patients. We demonstrate that MEDI3622
      is highly efficacious on tumor growth in multiple human CRC PDX models, resulting
      in improved survival of animals bearing tumor xenografts. MEDI3622 was further
      found to impact Notch pathway activity and tumor-initiating cells. The promising
      preclinical activity seen here supports further clinical investigation of this
      treatment approach to improve therapeutic outcome for patients diagnosed with
      metastatic CRC, including patients with KRAS-mutant tumors for whom other
      therapeutic options are currently limited.

PMID- 29029416
TI  - Detection of activating and acquired resistant mutation in plasma from EGFR
      mutated NSCLC patients by peptide nucleic acid (PNA) clamping-assisted
      fluorescence melting curve analysis.
AB  - This study was designed to prospectively examine whether peptide nucleic acid
      clamping-assisted fluorescence melting curve analysis (PANAMutyperTM) is feasible
      for the detection of activating and acquired resistant epidermal growth factor
      receptor (EGFR) mutation in plasma. Patients with non-small cell lung cancer
      harboring activating EGFR mutations who were scheduled to undergo EGFR-tyrosine
      kinase inhibitors (EGFR-TKIs) were enrolled between September 2011 and March
      2015. A total of 102 patients with EGFR-mutated lung cancer were enrolled, 53 had
      available plasma samples at disease progression, and 28 underwent serial plasma
      sampling during EGFR-TKI treatment. EGFR-TKI-sensitizing and T790M mutations were
      detected in the plasma of 68.6% (70/102) at baseline and 30.2% (16/53) at disease
      progression, respectively. The concordance rates for matched tissue and plasma
      samples were 80.4% and 90.2% for E19del and L858R mutations at baseline and 56.3%
      for T790M mutation at disease progression. The sustained presence of plasma EGFR
      mutations four weeks after EGFR-TKI predicted a poor objective response rate
      (30.0% vs. 87.5%, P = 0.025), as well as worse progression-free survival (hazard
      ratio [HR], 4.381) and overall survival (HR, 5.475). Longitudinal analysis could
      detect T790M mutations earlier than disease progression based on imaging study
      (median time from appearance of T790M in plasma samples to progression at imaging
      scan, 103 days). In conclusion, PANAMutyperTM is reliable for detecting
      activating and acquired resistant EGFR mutation in plasma, and predicts responses
      to EGFR-TKI via longitudinal monitoring of EGFR mutation during treatment.

PMID- 29029417
TI  - Anti-tumor activity of anthrax toxin variants that form a functional
      translocation pore by intermolecular complementation.
AB  - Anthrax lethal toxin is a typical A-B type protein toxin secreted by Bacillus
      anthracis. Lethal factor (LF) is the catalytic A-subunit, a metalloprotease
      having MEKs as targets. LF relies on the cell-binding B-subunit, protective
      antigen (PA), to gain entry into the cytosol of target cells. PA binds to cell
      surface toxin receptors and is activated by furin protease to form an LF-binding
      competent oligomer-PA pre-pore, which converts to a functional protein-conductive
      pore in the acidic endocytic vesicles, allowing translocation of LF into the
      cytosol. During PA pre-pore-to-pore conversion, the intermolecular salt bridge
      interactions between Lys397 and Asp426 on adjacent PA protomers play a critical
      role in positioning neighboring luminal Phe427 residues to form the Phe-clamp, an
      essential element of the PA functional pore. This essential intermolecular
      interaction affords the opportunity to create pairs of PA variants that depend on
      intermolecular complementation to form a functional pore. We have previously
      generated PA variants with furin-cleavage site replaced by substrate sequences of
      tumor-associated proteases, such as urokinase or MMPs. Here we show that PA-U2
      K397Q, a urokinase-activated PA variant with Lys397 residue replaced by
      glutamine, and PA-L1-D426K, a MMP-activated PA variant with Asp426 changed to
      lysine, do not form functional pores both in vitro or in vivo unless they are
      used together. Further, the mixture of PA-U2-K397Q and PA-L1-D426K displayed
      potent anti-tumor activity in the presence of LF. Thus, PA-U2-K397Q and PA-L1
      D426K form a novel intermolecular complementation system with toxin activation
      relying on the presence of two distinct tumor-associated proteases, i.e.,
      urokinase and MMPs.

PMID- 29029418
TI  - Identification of circulating microRNA signatures as potential noninvasive
      biomarkers for prediction and prognosis of lymph node metastasis in gastric
      cancer.
AB  - Circulating microRNAs (miRNAs) are emerging as novel noninvasive biomarkers for
      prediction of lymph node metastasis (LNM) in cancer. The aim of this study was to
      identify serum miRNA signatures for prediction and prognosis of LNM in gastric
      cancer (GC). MiSeq sequencing was performed for an initial screening of serum
      miRNAs in 10 GC patients with LNM, 10 patients without LNM and 10 healthy
      controls. Reverse transcription quantitative real-time PCR was applied to confirm
      concentration of candidate miRNAs using a training cohort (n = 279) and a
      validation cohort (n = 180). We identified a four-miRNA panel (miR-501-3p, miR
      143-3p, miR-451a, miR-146a) by multivariate logistic regression model that
      provided high predictive accuracy for LNM with an area under the receiver
      operating characteristic curve (AUC) of 0.891 (95% CI, 0.840 to 0.930) in
      training set. Prospective evaluation of this panel revealed an AUC of 0.822 (95%
      CI, 0.758 to 0.875, specificity = 87.78%, sensitivity = 63.33%) in validation
      set. Moreover, Kaplan-Meier analysis showed that LNM patients with low miR-451a
      and miR-146a levels had worse overall survival (OS) (p < 0.05). In Cox regression
      analysis, miR-451a was independently associated with OS of LNM (p = 0.028). Our
      results suggested that use of serum miRNAs seems promising in estimating the
      probability GC patients harbor LNM and providing prognostic information for LNM.

PMID- 29029419
TI  - CD44 regulates prostate cancer proliferation, invasion and migration via PDK1 and
      PFKFB4.
AB  - Our recent studies have shown that CD44, a cell-surface protein with functions in
      many biologic processes, involved in glucose metabolism of prostate cancer cells.
      However, the molecular mechanisms of the regulation need to be further
      elucidated. In present study, LNCaP cells infected with lentivirus vector
      overexpressing CD44. The expression levels of key enzymes in glucose metabolism
      known as PDK1 and PFKFB4 were determined using QRT-PCR and western blot. PDK1 and
      PFKFB4 in LNCaP and PC3 cells were knocked down with shRNA respectively, and then
      cell proliferation, invasion and cell migration assay were performed. We found
      that overexpression of CD44 increased expression levels of PDK1 and PFKFB4 in
      LNCaP cells. Silencing of PDK1 and PFKFB4 could decrease cell proliferation,
      inhibit invasion and migration ability of prostate cancer cells. In addition,
      CD44 inhibitor could decrease glucose consumption and increase ROS levels of PC-3
      cells significantly, as well as sensitize PC-3 cells to docetaxel. Taken
      together, CD44 could modulate aggressive phenotype of prostate cancer cells, by
      regulation of the expression of PDK1 and PFKFB4. CD44 may be a novel potential
      therapeutic target.

PMID- 29029420
TI  - Generation and evaluation of antibody agents for molecular imaging of CD44v6
      expressing cancers.
AB  - AIM: The aim of this study was to generate and characterize scFv antibodies
      directed to human CD44v6, as well as to radiolabel and evaluate top candidates in
      vitro and in vivo for their potential use in CD44v6-targeted molecular imaging in
      cancer patients. MATERIALS AND METHODS: Phage display selections were used to
      isolate CD44v6-specific scFvs. A chain shuffling strategy was employed for
      affinity maturation based on a set of CD44v6-specific first-generation clones.
      Two second-generation scFv clones were then chosen for labeling with 111In or
      125I and assessed for CD44v6-specific binding on cultured tumor cells. In vivo
      uptake and distribution was evaluated in tumor-bearing mice using a dual tumor
      model. Finally, a proof-of-concept small animal PET-CT study was performed on one
      of the candidates labeled with 124I. RESULTS: Two affinity-matured clones, CD44v6
      scFv-A11 and CD44v6-scFv-H12, displayed promising binding kinetics. Seven out of
      eight radiolabeled conjugates demonstrated CD44v6-specific binding. In vivo
      studies on selected candidates demonstrated very advantageous tumor-to-organ
      ratios, in particular for iodinated conjugates, where 125I-labeled scFvs
      exhibited favorable kinetics and tumor-to-blood ratios above five already at 24
      hours p.i.. The small animal PET-CT study using 124I-labeled CD44v6-scFv-H12 was
      in line with the biodistribution data, clearly visualizing the high CD44v6
      expressing tumor. CONCLUSION: The single chain fragments, CD44v6-scFv-A11 and
      CD44v6-scFv-H12 specifically bind to CD44v6, and the radiolabeled counterparts
      provide high tumor-to-blood ratios and fast clearance from organs and blood. We
      conclude that radioiodinated CD44v6-scFv-A11 and CD44v6-scFv-H12 possess features
      highly suitable for stringent molecular imaging.

PMID- 29029421
TI  - Prognostic value of supraclavicular nodes and upper abdominal nodes metastasis
      after definitive chemoradiotherapy for patients with thoracic esophageal squamous
      cell carcinoma.
AB  - The purpose of this study is to assess the prognostic value of supraclavicular
      nodes, left gastric nodes, celiac nodes and common hepatic nodes metastasis in
      esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. A
      total of 293 ESCC patients treated with radiotherapy or chemoradiotherapy entered
      the study. The results showed that the presence of supraclavicular nodes (chi2 =
      0.075, P = 0.785) and left gastric nodes (chi2 = 3.603, P = 0.058) metastasis had
      no significant influence on survival, while celiac nodes (chi2 = 33.775, P <
      0.001) and common hepatic nodes (chi2 = 42.350, P < 0.001) metastasis were
      associated with significantly shorter survival, regardless of the sites of
      primary tumor. Multivariate analysis showed that celiac nodes (HR: 0.457, 95% CI:
      0.256-0.816; P = 0.008) and common hepatic nodes (HR: 0.241, 95% CI: 0.092-0.630;
      P = 0.004) metastasis were independently adverse indicator of survival in upper
      ESCC. While in the middle and lower ESCC, only the common hepatic nodes (middle
      ESCC: HR: 0.345, 95% CI: 0.161-0.738, P = 0.006; lower ESCC: HR: 0.377, 95% CI:
      0.160-0.890, P = 0.026) metastasis was an independently adverse indicator of
      survival. In conclusion, our study demonstrated that in ESCC treated with
      definitive radiotherapy, both of celiac nodes and common hepatic nodes metastasis
      were adverse indicator of survival in upper ESCC, and common hepatic nodes
      metastasis were adverse indicator of survival in middle and lower ESCC.
      Supraclavicular nodes an left gastric nodes metastasis is not associated with
      patients survival in ESCC.

PMID- 29029422
TI  - Serine 207 phosphorylated lysyl-tRNA synthetase predicts disease-free survival of
      non-small-cell lung carcinoma.
AB  - It has been shown that various tRNA synthetases exhibit non-canonical activities
      unrelated to their original role in translation. We have previously described a
      signal transduction pathway in which serine 207 phosphorylated lysyl-tRNA
      synthetase (P-s207 LysRS) is released from the cytoplasmic multi-tRNA synthetase
      complex (MSC) into the nucleus, where it activates the transcription factor MITF
      in stimulated cultured mast cells and cardiomyocytes. Here we describe a similar
      transformation of LysRS due to EGFR signaling activation in human lung cancer.
      Our data shows that activation of the EGFR results in phosphorylation of LysRS at
      position serine 207, its release from the MSC and translocation to the nucleus.
      We then generated a P-s207 LysRS rabbit polyclonalantibody and tested 242 tissue
      micro-array samples derived from non-small-cell lung cancer patients. Highly
      positive nuclear staining for P-s207 LysRS was noted in patients with EGFR
      mutations as compared to WT EGFR patients and was associated with improved mean
      disease-free survival (DFS). In addition, patients with mutated EGFR and negative
      lymph node metastases had better DFS when P-s207 LysRS was present in the
      nucleus. The data presented strongly suggests functional and prognostic
      significance of P-s207 LysRS in non-small-cell lung cancer.

PMID- 29029423
TI  - DISC1 overexpression promotes non-small cell lung cancer cell proliferation.
AB  - Neuropsychiatric disorder-associated disrupted-in-schizophrenia-1 (DISC1)
      activates Wnt/beta-catenin signaling by inhibiting glycogen synthase kinase 3
      beta (GSK3beta) phosphorylation, and may promote neural progenitor cell and
      pancreatic beta-cell proliferation. The present study found that DISC1 promotes
      non-small cell lung cancer (NSCLC) cell growth. Western blotting and
      immunohistochemistry analyses showed that DISC1 was highly expressed in NSCLC
      cell lines and patient tissues. DISC1 expression was negatively associated with
      phosphorylated (p-) GSK3beta, but positively correlated with a more invasive
      tumor phenotype and predicted poor NSCLC patient prognosis. siRNA-mediated DISC1
      silencing increased p-GSK3beta expression and decreased expression of beta
      catenin and Cyclin D1, while DISC1 upregulation produced the opposite results.
      DISC1 knockdown also reduced NSCLC cell proliferation rates in vitro. These
      results suggest that DISC1 promotes NSCLC growth, likely through GSK3beta/beta
      catenin signaling, and that DISC1 may function as an oncogene and novel anti
      NSCLC therapeutic target.

PMID- 29029424
TI  - microRNA-22 can regulate expression of the long non-coding RNA MEG3 in acute
      myeloid leukemia.
AB  - AIM: Acute myeloid leukemia (AML) is the most common blood tumor with poor
      prognosis. At present, the research found that the pathogenesis of AML is related
      to many factors, such as recurrent somatic mutations and gene expression and
      epigenetic changes, however, the molecular mechanism of AML is still unclear.
      Long non-coding RNA MEG3 is a newly found tumor suppressor and plays a very
      important role in the regulation of a variety of tumor formation and progression.
      Studies found that the MEG3 expression was significantly decreased in AML.
      However, to date, it is not clear the cause of its abnormal expression.
      Therefore, the molecular mechanism of AML is urgently needed to study the
      molecular mechanism of AML. METHODS: The different expression level of MEG3,
      TET2, miR-22-3p, miR-22-5p in AML was detected by real-time quantification PCR.
      MEG3, TET2, miR-22-3p, miR-22-3p expression cell pools in K562 cells was used to
      interfering and TET2, MEG3 TET2, relations with miR-22-3p, miR-22-5p. The effect
      of AML cell on proliferation was evaluated by TET2 lower expression. RESULTS: 1.
      The lower expression of MEG3 and TET2 in AML cell lines was detected by RT-qPCR.
      2. The stable MEG3, TET2 overexpression cell pools in K562 cells was successful
      established. 3. After transfection, MTT assay revealed that cell growth was
      significantly increased in AML cell lines transfected with TET2 compared with
      controls. CONCLUSIONS: Our findings suggested that MEG3 is significantly down
      regulated in AML cell lines.

PMID- 29029425
TI  - MiR-346 suppresses cell proliferation through SMYD3 dependent approach in
      hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: The miRNAs are demonstrated to be involved in the
      carcinogenesis of hepatocellular carcinoma (HCC) and some exhibit potential value
      for oncotherapy. This study was designed to explore the role of miR-346 in the
      pathogenesis of hepatocellular carcinoma. METHODS: High throughput screening was
      employed following with Real time-PCR to investigate the candidate miRNAs. 5
      ethynyl-2-deoxyuridine (EdU) assay, CCK-8, transwell assay, cell cycle assay,
      luciferase reporter assay, western blot and mice xenotransplantation model were
      performed in the present study. RESULTS: We found miR-346 was significantly down
      regulated in the HCC tissues compared with the non-tumor controls and was
      associated with the tumor size and TNM grade. Additionally, the in vitro and in
      vivo assays confirmed that miR-346 suppressed the proliferation of HCC. Then,
      bioinformatic algorithms and luciferase reporter assays proved that miR-346
      directly targeted SET and MYND domain containing 3(SMYD3). We also performed the
      rescue experiments by inhibiting the expression of SMYD3 and found the down
      regulation of SMYD3 could neutralize the inhibitory effects of miR-346 on HCC. At
      last, the cox proportional hazards analysis showed that low expression of miR-346
      was an an independent prognostic factor for HCC. CONCLUSION: Our findings
      illuminated miR-346 targeting SMYD3 to inhibit the proliferation of HCC and its
      down-regulation predicts a poor prognosis.

PMID- 29029426
TI  - A20 functions as mediator in TNFalpha-induced injury of human umbilical vein
      endothelial cells through TAK1-dependent MAPK/eNOS pathway.
AB  - A20, a negative regulator of nuclear factor kappaB signaling, has been shown to
      attenuate atherosclerotic events. Transforming growth factor beta-activated
      kinase 1 (TAK1) plays a critical role in TNFalpha-induced atherosclerosis via
      endothelial nitric oxide (NO) synthase (eNOS) uncoupling and NO reduction. In the
      study, we investigated the hypothesis that A20 protected endothelial cell injury
      induced by TNFalpha through modulating eNOS activity and TAK1 signalling. Human
      umbilical vein endothelial cells (HUVECs) were stimulated by TNFalpha. The impact
      of A20 on cell apoptosis, eNOS expression and NO production and related TAK1
      pathway were detected. Both eNOS and NO production were remarkably reduced. TAK1,
      p38 MAPK phosphorylation and HUVECs apoptosis were enhanced after TNFalpha
      stimulation for 2 hrs. Inhibition of A20 significantly activated TAK1, p38 MAPK
      phosphorylation, and cell apoptosis, but blocked eNOS expression and NO
      production. Furthermore, p38 MAPK expression was suppressed by A20 over
      expression, but re-enhanced by inhibiting A20 or activation of TAK1. Furtherly,
      TNFalpha-induced suppression of eNOS and NO production were largely prevented by
      silencing p38 MAPK. Collectively, our results suggested that A20-mediated TAK1
      inactivation suppresses p38 MAPK and regulated MAPK/eNOS pathway, which
      contributes to endothelial cell survival and function preservation.

PMID- 29029427
TI  - Environment and bladder cancer: molecular analysis by interaction networks.
AB  - Bladder cancer (BC) is the 9th most common cancer worldwide, and the 6th most
      common cancer in men. Its development is linked to chronic inflammation, genetic
      susceptibility, smoking, occupational exposures and environmental pollutants. Aim
      of this work was to identify a sub-network of genes/proteins modulated by
      environmental or arsenic exposure in BC by computational network approaches. Our
      studies evidenced the presence of HUB nodes both in "BC and environment" and "BC
      and arsenicals" networks. These HUB nodes resulted to be correlated to circadian
      genes and targeted by some miRNAs already reported as involved in BC, thus
      suggesting how they play an important role in BC development due to environmental
      or arsenic exposure. Through data-mining analysis related to putative effect of
      the identified HUB nodes on survival we identified genes/proteins and their
      mutations on which it will be useful to focus further experimental studies
      related to the evaluation of their expression in biological matrices and to their
      utility as biomarkers of BC development.

PMID- 29029428
TI  - Long non-coding RNA TUG1 promotes cervical cancer progression by regulating the
      miR-138-5p-SIRT1 axis.
AB  - Increasing evidences showed that long non-coding RNAs (lncRNAs) play vital roles
      in tumor progression. Recent studies indicated that lncRNA TUG1 was upregulated
      and promoted tumor processes in several cancers. However, the expression and
      underlying mechanism of TUG1 in cervical cancer remain unclear. In the present
      study, we found that TUG1 expression was upregulated in cervical cancer tissues
      and correlated with advanced clinical features and poor overall survival. TUG1
      knockdown suppressed cervical cancer cell growth and metastasis in vitro and
      tumor growth in vivo. In addition, our results indicated that TUG1 could act as
      an endogenous sponge by directly binding to miR-138-5p and suppressed miR-138-5p
      expression. Furthermore, we found that TUG1 could reverse the inhibitory effect
      of miR-138-5p on cervical cancer cells processes, which might be involved in the
      activation of SIRT1, a target gene of miR-138-5p, and activation of Wnt/beta
      catenin signaling pathway. Taken together, we elucidated that TUG1 might promote
      cervical cancer malignant progression via miR-138-5p-SIRT1-Wnt/beta-catenin
      signaling pathway axis.

PMID- 29029429
TI  - Twist1 is highly expressed in cancer-associated fibroblasts of esophageal
      squamous cell carcinoma with a prognostic significance.
AB  - Cancer-associated fibroblasts (CAFs) play important roles in cancer progression.
      Twist1 was recently reported to be a key regulator of CAFs in gastric cancer, but
      its role in other types of cancer remains unclear, especially for esophageal
      squamous cell carcinoma (ESCC). We assessed the Twist1 expression on stromal
      fibroblasts using immunohistochemistry in 169 tissue specimens from ESCC
      patients, and performed in vitro and in vivo experiments to confirm the role of
      Twist1 in CAFs of ESCC. And we investigated the biological pathways that are
      activated in Twist1-high ESCC using The Cancer Genome Atlas (TCGA) data. The
      expression of Twist1 in stromal fibroblasts was observed in 89.9% of ESCC
      patients and positively associated with the increased depth of tumor invasion,
      lymph node metastasis, and advanced clinical stage, and a significant adverse
      prognostic factor in overall survival. Twist1-expressing stromal fibroblasts also
      expressed representative CAF markers, and co-localization of Twist1 and CAF
      markers were confirmed by confocal immunofluorescence imaging. Bioinformatic
      analysis of mRNA expression data of esophageal cancer from TCGA revealed that
      gene sets of CAFs were highly enriched in Twist1-high ESCC. Depletion of Twist1
      in ex vivo cultured ESCC CAFs induced significant decrease in migration,
      invasion, colony formation, sphere formation, and contractibility of ESCC cancer
      cells compared to control CAFs. Furthermore, Twist1-expressing fibroblasts
      remarkably enhanced the in vivo tumorigenicity of ESCC in a xenograft model. In
      conclusion, Twist1 could be a novel CAF marker for the prognostic evaluation of
      ESCC patients as well as a potent therapeutic target for ESCC.

PMID- 29029431
TI  - Does uneven geographic distribution of urologists effect bladder and prostate
      cancers mortality? National health insurance data in Korea from 2007-2011.
AB  - The relationship between distribution of urologists and mortality of bladder and
      prostate cancers has not been clearly established. The aim of this study was to
      investigate the relationship between uneven distribution of urologists and
      urologic cancer specific mortality at country level. Data from the National
      Health Insurance Service and National Statistical Office in Korea from 2007 to
      2011 were analyzed in this ecological study. Univariate and multivariable
      regression analyses were performed to determine risk factors for age standardized
      mortality rates (ASMR) of bladder and prostate cancers. Linear regression
      analysis showed a markedly (p < 0.001) uneven distribution of urologists between
      metropolitan and non-metropolitan areas. There was no significant difference in
      cancer specific ASMRs for either bladder cancer or prostate cancer. Univariate
      analysis after adjusting for time showed that country area, urologist density,
      and income were significant factors affecting bladder cancer incidence (p <
      0.001, p = 0.013, and p < 0.001, respectively). It also showed that the number of
      training hospitals was a significant factor for prostate cancer incidence (p =
      0.002). Although country area showed borderline significance (p = 0.056) for ASMR
      of bladder cancer, urologist density was not related to ASMR of bladder cancer or
      prostate cancer. Although there was a marked difference in urologist density
      between metropolitan and non-metropolitan areas for these years analyzed,
      mortality rates of bladder and prostate cancers were not significantly affected
      by country area or urologist density.

PMID- 29029430
TI  - Methylomics of nitroxidative stress on precancerous cells reveals DNA methylation
      alteration at the transition from in situ to invasive cervical cancer.
AB  - Epigenetic dysregulation is important in cervical cancer development, but the
      underlying mechanism is largely unknown. Increasing evidence indicates that DNA
      methylation is sensitive to changes in microenvironmental factors, such as nitric
      oxide (NO) in the chronic inflammatory cervix. However, the epigenomic effects of
      NO in cancer have not been investigated. In this study, we explored the
      methylomic effects of nitroxidative stress in HPV-immortalized precancerous
      cells. Chronic NO exposure promoted the acquisition of malignant phenotypes such
      as cell growth, migration, invasion, and anchorage-independent growth. Epigenetic
      analysis confirmed hypermethylation of PTPRR. Whole-genome methylation analysis
      showed BOLA2B, FGF8, HSPA6, LYPD2, and SHE were hypermethylated in cells. The
      hypermethylation BOLA2B, FGF8, HSPA6, and SHE was confirmed in cervical scrapings
      from invasive cancer, but not in CIN3/CIS, CIN2 and CIN1 (p=0.019, 0.023, 0.023
      and 0.027 respectively), suggesting the role in the transition from in situ to
      invasive process. Our results reveal that nitroxidative stress causes epigenetic
      changes in HPV-infected cells. Investigation of these methylation changes in
      persistent HPV infection may help identify new biomarkers of DNA methylation for
      cervical cancer screening, especially for precancerous lesions.

PMID- 29029432
TI  - The involvement of Nrf2 in the protective effects of (-)-Epigallocatechin-3
      gallate (EGCG) on NaAsO2-induced hepatotoxicity.
AB  - Arsenic exposure produces hepatotoxicity. The common mechanism determining its
      toxicity is the generation of oxidative stress. Oxidative stress induced by
      arsenic leads to the activation of nuclear factor erythroid 2-related factor 2
      (Nrf2) pathway. (-)-Epigallocatechin-3-gallate (EGCG) possesses a potent
      antioxidant capacity and exhibits extensive pharmacological activities. This
      study aims to evaluate effects of EGCG on arsenic-induced hepatotoxicity and
      activation of Nrf2 pathway. Plasma activities of alanine aminotransferase,
      aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase were
      measured; Histological analyses were conducted to observe morphological changes;
      Biochemical indexes such as oxidative stress (Catalase (CAT), malonyldialdehyde
      (MDA), superoxide dismutase (SOD), glutathione (GSH), reactive oxygen species
      (ROS)), Nrf2 signaling related genes (Nrf2, Nqo1, and Ho-1) were assessed. The
      results showed that EGCG inhibited arsenic-induced hepatic pathological damage,
      liver ROS level and MDA level. Arsenic decreases the antioxidant enzymes SOD,
      GPX, and CAT activity and the decrease was inhibited by treatment of EGCG.
      Furthermore, EGCG attenuated the retention of arsenic in liver tissues and
      improved the expressions of Nrf2 signaling related genes (Nrf2, Nqo1, and Ho-1).
      These findings provide evidences that EGCG may be useful for reducing
      hepatotoxicity associated with oxidative stress by the activation of Nrf2
      signaling pathway. Our findings suggest a possible mechanism of antioxidant EGCG
      in preventing hepatotoxicity, which implicate that EGCG may be a potential
      treatment for arsenicosis therapy.

PMID- 29029433
TI  - H2O2 attenuates IGF-1R tyrosine phosphorylation and its survival signaling
      properties in neuronal cells via NR2B containing NMDA receptor.
AB  - Impairment of insulin-like growth factor I (IGF-I) signaling plays an important
      role in the development of neurodegeneration. In the present study, we
      investigated the effect of H2O2 on the survival signaling of IGF-1 and its
      underlying mechanisms in human neuronal cells SH-SY5Y. Our results showed that
      IGF-1 promoted cell survival and stimulated phosphorylation of IGF-1R as well as
      its downstream targets like AKT and ERK1/2 in these cells. Meanwhile, these
      effects of IGF-1 were abolished by H2O2 at 200MUM concentration which did not
      cause any significant toxicity to cells itself in our experiments. Moreover,
      studies using various glutamate receptor subtype antagonists displayed that N
      methyl-D -aspartate (NMDA) receptor antagonist dizocilpine maleate (MK-801)
      blocked the effects of H2O2, whereas other glutamate receptor subtype
      antagonists, such as non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3
      dione (DNQX), metabolic glutamate receptor antagonists LY341495 and CPCCOEt, had
      no effect. Further studies revealed that NR2B-containing NMDARs are responsible
      for these effects as its effects were blocked by pharmacological inhibitor Ro25
      698 or specific siRNA for NR2B, but not NR2A. Finally, our data also showed that
      Ca2+ influx contributes to the effects of H2O2. Similar results were obtained in
      primary cultured cortical neurons. Taken together, the results from the present
      study suggested that H2O2 attenuated IGF-1R tyrosine phosphorylation and its
      survival signaling properties via NR2B containing NMDA receptors and Ca2+ influx
      in SH-SY5Y cells. Therefore, NMDAR antagonists, especially NR2B-selective ones,
      combined with IGF-1 may serve as an alternative therapeutic agent for oxidative
      stress related neurodegenerative disease.

PMID- 29029434
TI  - Silencing protein kinase C zeta by microRNA-25-5p activates AMPK signaling and
      inhibits colorectal cancer cell proliferation.
AB  - Developing novel strategies against human colorectal cancer (CRC) cells is
      needed. Activation of AMP-activated protein kinase (AMPK) could possibly inhibit
      CRC cells. Protein kinase C zeta (PKCzeta) is an AMPK negative regulator. Here we
      found that PKCzeta expression was significantly elevated in human colon cancer
      tissues and CRC cells. PKCzeta upregulation was correlated with AMPK in
      activation and mTOR complex 1 (mTORC1) over-activation. Reversely, PKCzeta shRNA
      knockdown activated AMPK signaling and inhibited HT-29 cell proliferation.
      Significantly, downregulation of microRNA-25-5p (miR-25-5p), a PKCzeta-targeting
      miRNA, could be the cause of PKCzeta upregulation. Exogenous expression of miR-25
      5p silenced PKCzeta to activate AMPK signaling, which inhibited HT-29 cell
      proliferation. In vivo studies showed that HT-29 xenograft growth in mice was
      inhibited after expressing PKCzeta shRNA or miR-25-5p. Collectively, PKCzeta
      could be a novel oncogenic protein of human CRC. PKCzeta silence, by targeted
      shRNA or miR-25-5p expression, activates AMPK and inhibits HT-29 cell
      proliferation.

PMID- 29029435
TI  - Anti-SSTR2 peptide based targeted delivery of potent PLGA encapsulated 3,3'
      diindolylmethane nanoparticles through blood brain barrier prevents glioma
      progression.
AB  - Current therapy for Glioblastoma is insufficient because of the presence of blood
      brain barrier. It limits the transport of essential drugs to the tumor sites. To
      overcome this limitation we strategized the delivery of an anticancer compound
      3,3'-diindolylmethane by encapsulation in poly (lactic-co-glycolic acid)
      nanoparticles. These nanoparticles were tagged with a novel peptide against
      somatostatin receptor 2 (SSTR2), a potential target in glioma. The
      nanoformulation (27-87nm) had loading and encapsulation efficiency of 7.2% and
      70% respectively. It was successfully internalized inside the glioma cells
      resulting in apoptosis. Furthermore, an in vivo bio-distribution study revealed
      the selective accumulation of the nanoformulation into rat brain tumor sites by
      crossing the blood brain barrier. This resulted in abrogation of epidermal growth
      factor receptor pathway activation in glioma cells. Our novel nanopreparation
      therefore shows great promise to serve as a template for targeted delivery of
      other therapeutics in treating GBM.

PMID- 29029436
TI  - XIST/miR-139 axis regulates bleomycin (BLM)-induced extracellular matrix (ECM)
      and pulmonary fibrosis through beta-catenin.
AB  - Pulmonary fibrosis (PF), characterized by the destruction of lung tissue
      architecture and the abnormal deposition of extracellular matrix (ECM) proteins,
      currently has no satisfactory treatment. In the present study, we investigated
      the hypothesis that XIST play a promotive role in bleomycin (BLM)-induced ECM and
      pulmonary fibrosis; XIST exerts its effect through miR-139 regulation. XIST
      expression was upregulated in lung tissues derived from BLM-induced mouse model
      of PF, and was positively correlated with beta-catenin and ECM protein levels,
      respectively. LV-sh-XIST-induced XIST knockdown led to decreased PF, reduced beta
      catenin and ECM protein levels in lung tissues. XIST knockdown suppressed the
      proliferation of IMR-90 (human fibroblast) and murine lung fibroblasts (MLFCs)
      and ECM protein expression. Moreover, miR-139 could directly bind to XIST and the
      3'UTR of beta-catenin; XIST competed with beta-catenin for miR-139 binding both
      in IMR-90 and MLFCs. In MLFCs, miR-139 inversely regulated XIST, and could
      partially reverse the effect of XIST on beta-catenin and ECM proteins. In lung
      tissues of PF mice, miR-139 expression was downregulated, whereas beta-catenin
      expression was upregulated. In conclusion, XIST exerts positive effects on BLM
      induced PF through inhibiting miR-139 to promote human/mouse fibroblast
      proliferation and ECM proteins.

PMID- 29029437
TI  - Long non-coding RNA UBE2CP3 promotes tumor metastasis by inducing epithelial
      mesenchymal transition in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a highly aggressive, solid malignancy that has
      a poor prognosis. Long non-coding RNAs (lncRNAs) have been found to be
      dysregulated in various cancers, including HCC. However, the molecular mechanism
      involving lncRNAs in HCC remains largely unknown. In this study, lncRNAs
      differentially expressed between HCC and corresponding non-cancerous tissue were
      identified by microarray analysis. A specific differentially expressed lncRNA
      UBE2CP3 (ubiquitin conjugating enzyme E2 C pseudogene 3) was identified. LncRNA
      UBE2CP3 was frequently up-regulated in HCC samples as assessed by quantitative
      real-time polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH)
      experiments. Clinical data showed that high levels of lncRNA UBE2CP3 were
      correlated with poor prognosis in HCC patients. Functional studies demonstrated
      that over-expression of lncRNA UBE2CP3 promoted cell invasion and migration in
      vitro and in vivo. Mechanistically, enhanced expression of lncRNA UBE2CP3
      increased the expression of Snail1 and N-cadherin, but decreased the expression
      of E-cadherin, thus promoting the process of epithelial to mesenchymal transition
      (EMT) and finally inducing cell invasion and migration. Furthermore, serum levels
      of lncRNA UBE2CP3 were increased in HCC patients and decreased after surgery. Our
      results suggest that lncRNA UBE2CP3 promotes the metastasis of HCC and that serum
      lncRNA UBE2CP3 may be a new biomarker for the diagnosis of HCC.

PMID- 29029438
TI  - Lipocalin 2 regulates intestine bacterial survival by interplaying with
      siderophore in a weaned piglet model of Escherichia coli infection.
AB  - Iron is an essential nutrient that facilitates cell proliferation and growth,
      which plays a pivotal role in modulating the battle for survival between
      mammalian hosts and their pathogens. Pathogenic bacteria secrete siderophores to
      acquire iron from the host. However, lipocalin 2 (Lcn2), a siderophore-binding
      antimicrobial protein, binds to siderophores to prevent bacterial uptake of iron,
      which is critical for the control of systemic infection with Escherichia coli (E.
      coli). But few studies focus on the anti-infective response of Lcn2 in the
      intestines by inhibiting bacterial proliferation based on microbial iron
      metabolism. In this study, we showed that iron was sequestrated within cells in a
      piglet model of E. coli K88 infection. Siderophores was produced following E.
      coli K88 infection and siderophore-related genes expression was upregulated in
      iron-deficiency environment in vitro. Meanwhile, we found that Lcn2 expression
      was rapidly and robustly induced in jejunum by E. coli K88 infection and could be
      stimulated by IL-17 and IL-22. Furthermore, both Lcn2 induced in epithelial cells
      IPEC-1 and added exogenously as a recombinant protein could inhibit the growth of
      E. coli. We can conclude that Lcn2 is a crucial component of mucosal immune
      defense against intestinal infection with E. coli K88.

PMID- 29029439
TI  - MicroRNA-149* suppresses hepatic inflammatory response through antagonizing STAT3
      signaling pathway.
AB  - Chronic inflammation is increasingly recognized as an important component of
      tumorigenesis and metabolic diseases. The roles of microRNA149* (miRNA149*) in
      inflammation remain poorly understood. Here, we demonstrate that miR-149* is a
      suppressor of STAT3-mediated inflammation. MiR-149*-/- mice were generated with
      CRISPR/CAS9 technique. In a lipopolysaccharide (LPS)-induced inflammation model,
      miR-149*-/- mice show more severe liver injury and inflammation, compared with
      wild-type (WT) mice. MiR-149*-/- mice also displayed elevated messenger RNA
      (mRNA) levels of interleukin (IL)-6, inducible nitric oxide synthase (iNOS),
      complement C3 (C3) and IL-4 in response to LPS. Then miR-149* agomir
      administration is largely able to alleviate the LPS-induced some inflammatory
      gene expression in WT mouse liver. In vitro, miR-149* mimics inhibited expression
      of STAT3-meidated inflammatory mediators induced by LPS and suppresses the
      phosphorylation of STAT3 and its transcription activity in HepG2 cells. These
      findings identify miR-149* as a negative mediator of inflammation that may serve
      as an attractive therapeutic tool for immune and inflammatory liver diseases.

PMID- 29029440
TI  - Colorectal carcinoma with osseous metaplasia.
AB  - Osseous metaplasia (OM) is rarely observed in colorectal cancer (incidence < 0.4%
      in rectal cancer), where it has a non-specific clinical presentation and unknown
      pathogenesis. Here, we report three cases of colorectal carcinoma with OM and
      propose a new hypothesis. All three patients (two males and one female) were
      Chinese and had different sites of colorectal carcinoma with OM: rectum, sigmoid
      colon, and appendix. The pathologic diagnoses were serrated adenocarcinoma;
      moderately to poorly differentiated adenocarcinoma with micropapillary carcinoma
      and cribriform comedo-type adenocarcinoma; and mucinous adenocarcinoma,
      respectively. Clinical follow-up showed that one patient died 5 months after
      surgery, but the others are alive after 68 months and 53 months.
      Immunohistochemistry revealed that CD44, MAPK, MDM2, OPN and PEDF were expressed
      by both tumor cells and stromal cells, while P53 was expressed only by tumor
      cells. KRAS/NRAS/BRAF genotyping revealed different KRAS mutations in each of the
      three cases, but the NRAS and BRAF exons were all wild-type. These findings
      suggest OM has no relation with NRAS and BRAF mutation, and it is uncertain
      whether there is a relationship between ossification and KRAS mutation. OPN,
      MAPK, MDM2, P53, PEDF and CD44 may act as osteogenic factors in colorectal cancer
      with OM.

PMID- 29029441
TI  - Curcumin protects against hepatic ischemia/reperfusion induced injury through
      inhibiting TLR4/NF-kappaB pathway.
AB  - The TLR4/NF-kappaB pathway had important roles in hepatic ischemia/reperfusion
      (I/R) injury. In this study, we reported a protective effect of curcumin against
      hepatic I/R injury via TLR4/NF-kappaB pathway. Curcumin significantly inhibited
      cell apoptosis, and decreased levels of LDH and production of TNF-a, IL-1b, and
      IL-6 in the cell supernatant. In addition, curcumin ameliorated elevated TLR4 and
      NF-kappaB caused by hypoxia/reoxygenation stimulation in BRL-3A cells. In vivo
      assays revealed that curcumin reduce levels of ALT and AST, and reversed TLR4/NF
      kappaB signaling pathway caused by hepatic I/R stimulation in liver tissues.
      These results suggested that curcumin ameliorates hepatic I/R injury, which may
      be mediated in part via the TLR4/NF-kappaB signaling pathway.

PMID- 29029442
TI  - Transcriptomic profiling of long non-coding RNAs in hepatitis B virus-related
      hepatocellular carcinoma.
AB  - Long non-coding RNAs (lncRNAs) have been reported to be involved in the
      development and progression of hepatocellular carcinoma (HCC). However, few
      studies have focus on the dyregulation and the role of lncRNAs in HBV-related
      HCC. We performed a comprehensive analysis of lncRNAs expression profile in HBV
      related HCC tissues samples using deep sequencing. We revealed that a total of
      1242 lncRNA transcripts (983 up-regulated and 259 down-regulated) and 1841 mRNA
      transcripts were significantly differentially expressed in HBV-related HCC
      patients. Pathway and gene ontology analysis showed that they are involved in the
      biological process related to HCC development by cis-regulation of co-expressed
      protein-coding genes. 10 candidate lncRNAs were selected and validated with
      quantitative real-time PCR analysis. Furthermore, we found that one of most down
      regulated lncRNAs, n346077, could suppress HCC cells invasion and migration in
      vitro. Our findings provide an overview of aberrantly expressed lncRNAs in HBV
      related HCC and will be useful for further functional studies of lncRNAs in HBV
      related pathogenesis.

PMID- 29029443
TI  - Quantitative evaluation of Gd-EOB-DTPA uptake in focal liver lesions by using T1
      mapping: differences between hepatocellular carcinoma, hepatic focal nodular
      hyperplasia and cavernous hemangioma.
AB  - OBJECTIVES: To investigate the difference of T1 relaxation time on Gd-EOB-DTPA
      enhanced MRI in hepatocellular carcinoma (HCC), hepatic focal nodular hyperplasia
      (FNH) and cavernous hemangioma of liver (CHL), and to quantitatively evaluate the
      uptake of Gd-EOB-DTPA in these three focal liver lesions (FLLs). RESULTS: The T1P
      of CHL was significantly higher than those of HCC and FNH (P < 0.05). Reduction
      of T1 relaxation time on hepatobiliary phase could be observed in all three types
      of lesions. There were significant differences of T1P, T1E, T1D and T1D% between
      FNH, CHL and HCC (P < 0.001). Spearman correlation analysis revealed that T1D%
      was the best indicator for diagnostic differentiation, with a correlation
      coefficient of 0.702. Discriminant analysis using three variables (T1P, T1E, and
      T1D%) showed that the classification accuracy was 88.2%. MATERIALS AND METHODS:
      74 patients diagnosed with focal liver lesions underwent Gd-EOB-DTPA-enhanced MRI
      including T1 mapping were enrolled, consisting of 51 HCCs, 10 FNHs, and 13 CHLs.
      T1 relaxation times of these lesions were measured on pre-contrast (T1P) and on
      hepatobiliary phase images at 20 minute after contrast (T1E). The reduction of T1
      relaxation time on hepatobiliary (T1D) and the percentage reduction (T1D%) was
      calculated. The differences of T1P, T1E, T1D and T1D% in these FLLs were
      analyzed. The usefulness of these parameters for classification of FLLs was
      evaluated. CONCLUSIONS: Uptake of Gd-EOB-DTPA is different between in HCC, FNH
      and CHL. These three lesions can be distinguished using T1 mapping.

PMID- 29029444
TI  - The prohibitin protein complex promotes mitochondrial stabilization and cell
      survival in hematologic malignancies.
AB  - Prohibitins (PHB1 and PHB2) have been proposed to play important roles in cancer
      development and progression, however their oncogenic mechanism of action has not
      been fully elucidated. Previously, we showed that the PHB1 and PHB2 protein
      complex is required for mitochondrial homeostasis and survival of normal human
      lymphocytes. In this study, novel evidence is provided that indicates
      mitochondrial prohibitins are overexpressed in hematologic tumor cells and
      promote cell survival under conditions of oxidative stress. Immunofluorescent
      confocal microscopy revealed both proteins to be primarily confined to
      mitochondria in primary patient lymphoid and myeloid tumor cells and tumor cell
      lines, including Kit225 cells. Subsequently, siRNA-mediated knockdown of PHB1 and
      PHB2 in Kit225 cells significantly enhanced sensitivity to H2O2-induced cell
      death, suggesting a protective or anti-apoptotic function in hematologic
      malignancies. Indeed, PHB1 and PHB2 protein levels were significantly higher in
      tumor cells isolated from leukemia and lymphoma patients compared to PBMCs from
      healthy donors. These findings suggest that PHB1 and PHB2 are upregulated during
      tumorigenesis to maintain mitochondrial integrity and therefore may serve as
      novel biomarkers and molecular targets for therapeutic intervention in certain
      types of hematologic malignancies.

PMID- 29029445
TI  - MicroRNA-200c increases radiosensitivity of human cancer cells with activated
      EGFR-associated signaling.
AB  - MicroRNA-200c (miR-200c) recently was found to have tumor-suppressive properties
      by inhibiting the epithelial-mesenchymal transition (EMT) in several cancers. miR
      200c also interacts with various cellular signaling molecules and regulates many
      important signaling pathways. In this study, we investigated the radiosensitizing
      effect of miR-200c and its mechanism in a panel of human cancer cell lines.
      Malignant glioma (U251, T98G), breast cancer (MDA-MB-468), and lung carcinoma
      (A549) cells were transfected with control pre-microRNA, pre-miR-200c, or anti
      miR-200c. Then, RT-PCR, clonogenic assays, immunoblotting, and immunocytochemisty
      were performed. To predict the potential targets of miR-200c, microRNA databases
      were used for bioinformatics analysis. Ectopic overexpression of miR-200c
      downregulated p-EGFR and p-AKT and increased the radiosensitivity of U251, T98G,
      A549, and MDA-MB-468 cells. In contrast, miR-200c inhibition upregulated p-EGFR
      and p-AKT, and decreased radiation-induced cell killing. miR-200c led to
      persistent gammaH2AX focus formation and downregulated pDNA-PKc expression.
      Autophagy and apoptosis were major modes of cell death. Bioinformatics analysis
      predicted that miR-200c may be associated with EGFR, AKT2, MAPK1, VEGFA, and
      HIF1AN. We also confirmed that miR-200c downregulated the expression of VEGF, HIF
      1alpha, and MMP2 in U251 and A549 cells. In these cells, overexpressing miR-200c
      inhibited invasion, migration, and vascular tube formation. These phenotypic
      changes were associated with E-cadherin and EphA2 downregulation and N-cadherin
      upregulation. miR-200c showed no observable cytotoxic effect on normal human
      fibroblasts and astrocytes. Taken together, our data suggest that miR-200c is an
      attractive target for improving the efficacy of radiotherapy via a unique
      modulation of the complex regulatory network controlling cancer pro-survival
      signaling and EMT.

PMID- 29029446
TI  - A potential prognostic biomarker SPC24 promotes tumorigenesis and metastasis in
      lung cancer.
AB  - RESULTS: SPC24 is over-expressed in clinical lung adenocarcinoma samples, and
      high level of SPC24 is associated with advanced stages of lung tumors. Knocking
      down SPC24 repressed cell growth and promoted apoptosis. SPC24 deficiency reduced
      cancer cell migration as well. E-cadherin, one of the epithelial-mesenchymal
      transition markers, was up-regulated in the knockdown cells, along with down
      regulation of N-cadherin and Vimentin. Oncomine expression analyses further
      confirmed that high level of SPC24 is associated with tumors from smokers,
      recurrent patients, or patients with shorter survivals. PURPOSE AND METHODS: To
      reveal the role of SPC24, an important component of kinetochore, in the
      tumorigenesis of lung cancer, we performed Oncomine and immunohistochemistry
      (IHC) analyses for SPC24 in human lung adenocarcinoma tumors. We knocked down
      SPC24 in two non-small cell lung cancer (NSCLC) cell lines, PC9 and A549, by
      siRNA and evaluated cell proliferation, apoptosis, and migration in the SPC24
      deficient cells. Using a mouse xenograft model, we compared in vivo tumor growth
      of the knockdown and control cells. We further performed multiple Oncomine
      expression analyses for SPC24 in various lung cancer datasets with important
      clinical characteristics and risk factors, including survival, recurrence, and
      smoking status. CONCLUSIONS: SPC24 is a novel oncogene of lung cancer, and can
      serve as a promising prognostic biomarker to differentiate lung tumors that have
      various clinicopathological characteristics. The findings of the current study
      will benefit the diagnosis, management, and targeted therapy of lung cancer.

PMID- 29029447
TI  - The association between renal sinus fat area and the progression-free survival in
      Chinese non-metastatic clear-cell renal cell carcinoma patients.
AB  - In this retrospective study, we evaluated the association between renal sinus fat
      area (RSFA) and survival in 268 Chinese non-metastatic clear-cell renal cell
      carcinoma (ccRCC) patients. Patients with high RSFA exhibited better progression
      free survival than those with low RSFA in both univariable (HR: 0.240; 95% CI:
      0.119-0.482; p < 0.001) and multivariable (HR: 0.432; 95% CI: 0.369-2.749; p =
      0.027) analyses. A propensity-score matched (PSM) analysis using Kaplan-Meier
      curves confirmed our findings (log-rank test; p = 0.028). Based on the
      multivariable analysis, we constructed a prognostic nomogram with 4 factors,
      namely, RSFA, Fuhrman grade, AJCC stage and sarcomatoid component. The c-index
      values for the Leibovich scoring system and the nomogram were 0.762 (95%CI, 0.688
      0.835) and 0.823 (95%CI, 0.759-0.888), respectively. These findings demonstrate
      that high RSFA is associated with better progression-free survival in non
      metastatic ccRCC.

PMID- 29029448
TI  - Risk-stratified surveillance and cost effectiveness of follow-up after radical
      cystectomy in patients with muscle-invasive bladder cancer.
AB  - BACKGROUND: The recurrence risk stratification and the cost effectiveness of
      oncological surveillance after radical cystectomy are not clear. We aimed to
      develop a risk stratification and a surveillance protocol with improved cost
      effectiveness after radical cystectomy. RESULTS: Of 581 enrolled patients, 175
      experienced disease recurrences. The pathology-based protocol presented
      significant differences in recurrence-free survival between normal- and high-risk
      patients, but the medical expense was high, especially in normal-risk (<=pT2pN0)
      patients. Cox regression analysis identified six factors associated with
      recurrence-free survival. Risk score-based 5-year follow-up was significantly
      more cost effective than the pathology-based protocol. MATERIALS AND METHODS: We
      retrospectively evaluated 581 patients with radical cystectomy for muscle
      invasive bladder cancer at 4 hospitals. Patients with routine oncological follow
      up were stratified into normal- and high-risk groups by a pathology-based
      protocol utilizing pT, pN, lymphovascular invasion, and histology. Cost
      effectiveness of the pathology-based protocol was evaluated and a risk-score
      based protocol was developed to optimize cost effectiveness. Risk-scores were
      calculated by summing risk factors independently associated with recurrence-free
      survival. Patients were stratified by low-, intermediate-, and high-risk score.
      Estimated cost per one recurrence detection by the pathology and by risk-scores
      were compared. CONCLUSIONS: Risk-score-stratified surveillance protocol has
      potential to reduce over-evaluation after radical cystectomy without adverse
      effects on medical cost.

PMID- 29029450
TI  - New insights in the clinical and translational relevance of miR483-5p in
      adrenocortical cancer.
AB  - Adrenocortical cancer (ACC) is a rare aggressive malignancy. Recent ACC
      integrated genomics analysis contributed to redefine the risk groups on molecular
      basis, including tumor microRNAs (miRs), detectable also in the bloodstream. We
      developed a quantitative real-time (RT) assay for the measurement of miR483 and
      miR483-5p absolute levels in plasma samples. miR483/miR483-5p levels were
      evaluated in plasma samples of 27 patients with ACC before surgery and at follow
      up. Statistically significant differences in miR483-5p and miR483 levels were
      found between stage 1/2 and stage 3/4 ACCs in pre-surgery and post-surgery
      samples. ROC curve analysis of miR483-5p levels gave a prediction of the clinical
      stage (accuracy 0.917+/-0.084), with the best cut-off value of 0.221 ng/ml,
      prognosticating overall and recurrence-free survival. In a multivariate Cox
      analysis (HR 16.2, 95%CI[1.39-188.6, P<0.026]), miR483-5p was the only variable
      that significantly predicted recurrence, but not overall survival. In addition,
      miR483 and miR483-5p levels correlated with the number of circulating tumor cells
      (CTCs) detected in the same blood samples, independently of the timing of
      sampling. In conclusion, we demonstrated that miR483-5p absolute plasma levels in
      ACC patients are powerful molecular markers that may help in the follow-up of
      patients after surgery and chemotherapy, and contribute to more accurately
      classify and predict tumor progression.

PMID- 29029449
TI  - Disrupted small-world brain network topology in pure conduct disorder.
AB  - OBJECTIVES: Conduct disorder (CD) is characterized by the violation of the rights
      of others or basic social rules and a repetitive, persistent pattern of
      antisocial and aggressive behaviors. A large number of functional and structural
      neuroimaging studies have identified widely abnormalities in specific brain
      regions in CD, but the alterations in the topological organization of functional
      networks among them remain largely unknown. METHODS: Resting-state functional
      magnetic resonance imaging was applied to investigate the intrinsic functional
      connectivity in 18 pure CD patients and eighteen typically developing healthy
      controls. We first constructed the functional networks and then examined the CD
      related alteration in topology properties using graph theoretical analysis.
      RESULTS: Both the CD group and healthy controls exhibited small-world topology.
      However, the CD group showed decreased global and local efficiency. Changes in
      the nodal characteristics in CD group were found predominantly in the default
      mode network, visual, and striatum regions. In addition, altered fronto-limbic
      striatum network topology was found to have a relationship with clinical scores.
      CONCLUSIONS: Our findings indicate the altered nodal topology of brain functional
      connectivity networks in CD. SIGNIFICANCE: The results provide unequivocal
      evidence of a topological disruption in the brain networks that suggest some
      possible pathophysiological mechanisms underlying CD.

PMID- 29029451
TI  - Transcriptome analysis reveals a role for the endothelial ANP-GC-A signaling in
      interfering with pre-metastatic niche formation by solid cancers.
AB  - Cancer establishes a microenvironment called the pre-metastatic niche in distant
      organs where disseminated cancer cells can efficiently metastasize. Pre
      metastatic niche formation requires various genetic factors. Previous studies
      suggest that inhibiting a single niche-factor is insufficient to completely block
      pre-metastatic niche formation especially in human patients. Here we show that
      the atrial natriuretic peptide (ANP), an endogenous hormone produced by the
      heart, inhibits pre-metastatic niche formation and metastasis of murine solid
      cancer models when pharmacologically supplied in vivo. On the basis of a wealth
      of comprehensive RNA-seq data, we demonstrated that ANP globally suppressed
      expression of cancer-induced genes including known niche-factors in the lung. The
      lungs of mice overexpressing GC-A, a receptor for ANP in endothelial cells, were
      conferred resistance against pre-metastatic niche formation. Importantly, neither
      ANP administration nor GC-A overexpression had a detrimental effect on lung gene
      expression in a cancer-free condition. The current study establishes endothelial
      ANP-GC-A signaling as a therapeutic target to control the pre-metastatic niche.

PMID- 29029452
TI  - The H3K27me3-demethylase KDM6A is suppressed in breast cancer stem-like cells,
      and enables the resolution of bivalency during the mesenchymal-epithelial
      transition.
AB  - The deposition of the activating H3K4me3 and repressive H3K27me3 histone
      modifications within the same promoter, forming a so-called bivalent domain,
      maintains gene expression in a repressed but transcription-ready state. We
      recently reported a significantly increased incidence of bivalency following an
      epithelial-mesenchymal transition (EMT), a process associated with the initiation
      of the metastatic cascade. The reverse process, known as the mesenchymal
      epithelial transition (MET), is necessary for efficient colonization. Here, we
      identify numerous genes associated with differentiation, proliferation and
      intercellular adhesion that are repressed through the acquisition of bivalency
      during EMT, and re-expressed following MET. The majority of EMT-associated
      bivalent domains arise through H3K27me3 deposition at H3K4me3-marked promoters.
      Accordingly, we show that the expression of the H3K27me3-demethylase KDM6A is
      reduced in cells that have undergone EMT, stem-like subpopulations of mammary
      cell lines and stem cell-enriched triple-negative breast cancers. Importantly,
      KDM6A levels are restored following MET, concomitant with CDH1/E-cadherin
      reactivation through H3K27me3 removal. Moreover, inhibition of KDM6A, using the
      H3K27me3-demethylase inhibitor GSK-J4, prevents the re-expression of bivalent
      genes during MET. Our findings implicate KDM6A in the resolution of bivalency
      accompanying MET, and suggest KDM6A inhibition as a viable strategy to suppress
      metastasis formation in breast cancer.

PMID- 29029453
TI  - PTEN loss detection in prostate cancer: comparison of PTEN immunohistochemistry
      and PTEN FISH in a large retrospective prostatectomy cohort.
AB  - PTEN deletion is an established prognostic biomarker in prostate cancer. We
      compared PTEN immunohistochemistry (IHC) and PTEN fluorescence in situ
      hybridization (FISH) in the largest existing radical prostatectomy cohort with
      clinical follow-up data. There was high concordance between IHC and FISH: 93%
      (3098/3330) of tumors with intact PTEN IHC showed absence of PTEN gene deletion
      and 66% (720/1087) of cases with PTEN protein loss by IHC showed PTEN gene
      deletion by FISH. 84% (447/533) of cases with PTEN homozygous gene deletion had
      PTEN protein loss by IHC. PTEN loss by IHC was associated with reduced PSA
      recurrence-free survival (RFS) in multivariable models (HR=1.3; 95% CI: 1.16
      1.47). Among cases with either PTEN deletion or absence of PTEN deletion by FISH,
      PTEN loss by IHC was strongly associated with reduced RFS on univariable analysis
      (p=0.0005 and p<0.0001 respectively). Among cases with intact PTEN by IHC,
      homozygous (p=0.04) but not heterozygous (p=0.10) PTEN gene deletion was weakly
      associated with reduced RFS. Among cases with PTEN loss by IHC, both homozygous
      (p=0.0044) and heterozygous (p=0.0017) PTEN gene deletion were associated with
      reduced RFS. These data support the utility of PTEN IHC and PTEN FISH as
      complementary screening tools for PTEN loss in prostate cancer.

PMID- 29029454
TI  - Long noncoding RNA AB073614 promotes the malignance of glioma by activating
      Wnt/beta-catenin signaling through downregulating SOX7.
AB  - Long noncoding RNA (lncRNA) AB073614 has recently shown to be aberrantly
      increased and identified as a poor prognostic biomarker in human glioma. However,
      the potential mechanisms remain unknown. This study demonstrated that AB073614
      expression was significantly upregulated in both glioma tissues and cell lines,
      and glioma patients with high AB073614 expression had lower overall survival
      rates. Importantly, silencing AB073614 expression remarkably inhibited U251 cell
      proliferation, migration, and invasion in vitro, as well as suppressed tumor
      formation in vivo. The level of AB073614 was found to correlate inversely with
      sex-determining region Y-box 7 (SOX7) expression but correlate positively with
      Wnt/beta-catenin signaling activity. Of note, the data showed that the inhibition
      of SOX7 could reverse the tumor-suppressive effect of the silencing AB073614 on
      glioma in vitro and in vivo. Furthermore, the results indicated that AB073614
      induced Wnt/beta-catenin signaling activity by repressing SOX7 expression. In
      conclusion, the findings demonstrated that AB073614 promoted the progression of
      glioma by targeting SOX7 to activate the Wnt/beta-catenin signaling pathway,
      suggesting that the inhibition of AB073614 might be a potential target for
      therapeutic intervention in glioma patients.

PMID- 29029455
TI  - Mobilization studies in mice deficient in sphingosine kinase 2 support a crucial
      role of the plasma level of sphingosine-1-phosphate in the egress of
      hematopoietic stem progenitor cells.
AB  - Sphingosine-1-phosphate (S1P) is a bioactive lipid involved in cell signaling
      and, if released from cells, also plays a crucial role in regulating the
      trafficking of lympho-hematopoietic cells, including primitive hematopoietic
      stem/progenitor cells (HSPCs). It has been demonstrated that S1P chemoattracts
      HSPCs, and its level in peripheral blood creates a gradient directing egress of
      these cells during mobilization. In this paper we analyzed hematopoiesis in mice
      deficient in sphingosine kinase 2 (Sphk2-KO mice) and studied the effect of this
      mutation on plasma S1P levels. We found that Sphk2-KO mice have normal
      hematopoiesis, and, in contrast to Sphk1-KO mice, the circulating S1P level is
      highly elevated in these animals and correlates with the fact that HSPCs in Sphk2
      KO animals, also in contrast to Sphk1-KO animals, show enhanced mobilization.
      These results were recapitulated in wild type (WT) animals employing an Sphk2
      inhibitor. We also administered an inhibitor of the S1P-degrading enzyme S1P
      lyase, known as tetrahydroxybutylimidazole (THI), to WT mice and observed that
      this resulted in an increase in S1P level in PB and enhanced mobilization of
      HSPCs. In sum, our results support a crucial role for S1P gradients in blood
      plasma in the mobilization process and indicate that small-molecule inhibitors of
      Sphk2 and Sgpl1 could be employed as mobilization-facilitating compounds. At the
      same time, further studies are needed to explain the unexpected effect of Sphk2
      inhibition on increasing S1P levels in plasma.

PMID- 29029457
TI  - Prognostic relevance of protein expression, clinical factors, and MYD88 mutation
      in primary bone lymphoma.
AB  - Primary bone lymphomas (PBLs) are composed of malignant lymphoid cells presenting
      in osseous sites, without supra-regional lymph node or extranodal involvement. We
      systematically characterized the immunophenotype and the myeloid differentiation
      factor 88 (MYD88)-L265P gene mutation status in PBL. Clinical data from 19
      patients with PBL treated at Nanjing Drum Tower Hospital between 2009 and 2015
      were analyzed retrospectively. Protein expression patterns were identified
      immunohistochemically, and MYD88 mutation was assessed using polymerase chain
      reaction and direct DNA sequencing. Fifteen patients presented with diffuse large
      B-cell lymphoma. Clinical factors favoring a good prognosis were an age < 60
      years and rituximab treatment. B-cell lymphoma 2 expression was detected in 5/15
      diffuse large B-cell lymphoma patients, and was associated with a poor prognosis
      in a univariate model. Janus kinase/signal transducer and activator of
      transcription 3 (JAK/STAT3) signaling factors were upregulated in PBLs. All
      eighteen evaluable PBL samples harbored wild-type MYD88. These data thus suggest
      that age and rituximab treatment are independent prognostic factors determining
      overall survival, and that activation of JAK/STAT3 signaling may promote the
      pathogenesis of PBL. Moreover, the absence of MYD88-L265P mutation in PBL
      indicate there are distinct pathogenetic backgrounds among extranodal lymphomas.

PMID- 29029456
TI  - Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene single nucleotide
      polymorphisms and its interaction with T2DM on pulmonary tuberculosis in Chinese
      Uygur population.
AB  - AIMS: To investigate the association of several single nucleotide polymorphisms
      (SNPs) within Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene and
      additional gene- gene and gene- type 2 diabetes mellitus (T2DM) interaction with
      pulmonary tuberculosis (PTB) risk in Chinese Uygur population. METHODS: A total
      of 722 participants (186 males, 536 females) were selected, including 360 PTB
      patients and 362 control participants. Generalized multifactor dimensionality
      reduction (GMDR) was used to screen the best interaction combination among SNPs
      and T2DM. Logistic regression was performed to investigate association between 3
      SNPs within PTPN22 gene, additional gene- gene and gene- T2DM interaction on PTB
      risk. RESULTS: Logistic regression analysis showed that PTB risk was
      significantly lower in carriers with rs2476601- CT genotype than those with CC
      genotype (CT versus CC), adjusted OR (95%CI) =0.42 (0.17-0.83), and higher in
      carriers with the rs33996649- GA genotype than those with GG genotype (GA versus
      GG), adjusted OR (95%CI) = 5.66 (2.24-9.47). We found a significant two-locus
      model (p=0.0010) involving rs33996649 and T2DM. Overall, the cross-validation
      consistency of this two- locus model was 10/ 10, and the testing accuracy was
      60.11%. We also conducted stratified analysis for rs33996649 and T2DM using
      logistic regression. We found that T2DM patients with rs33996649 - GA genotype
      have the highest PTB risk, compared to non- T2DM patients with rs33996649- GG
      genotype, OR (95%CI) = 4.52 (2.71 -6.43), after covariates adjustment.
      CONCLUSIONS: We found that the T allele of rs2476601 and the A allele of
      rs33996649within PTPN22 gene, interaction between rs2476601 and T2DM were all
      associated with increased PTB risk.

PMID- 29029458
TI  - LMO1 polymorphisms reduce neuroblastoma risk in Chinese children: a two-center
      case-control study.
AB  - Previous genome-wide association and validation studies suggest that LIM domain
      only 1 (LMO1) gene polymorphisms affect neuroblastoma susceptibility. In this
      work, we used Taqman methodology to genotype four LMO1 polymorphisms (rs110419 A
      > G, rs4758051 G > A, rs10840002 A > G and rs204938 A > G) in 118 neuroblastoma
      cases and 281 controls from Northern China. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were used to evaluate the association. We found that rs4758051 G
      > A was associated with a decreased neuroblastoma risk (AA vs. GG: adjusted OR =
      0.28, 95% CI = 0.13-0.62; AG/AA vs. GG: adjusted OR = 0.62, 95% CI = 0.40-0.97;
      AA vs. GG/AG: adjusted OR = 0.33, 95% CI = 0.15-0.69). Likewise, carrying the
      rs10840002 G allele was also associated with a decreased neuroblastoma risk in
      this Northern Chinese population. In a combination analysis using Southern and
      Northern Chinese populations, we found that those carrying the rs110419 G,
      rs4758051 A or rs10840002 G allele were at decreased neuroblastoma risk, and this
      finding was supported by a false-positive report probability analysis. These
      results further verify that LMO1 polymorphisms are protective against
      neuroblastoma. Case-control studies with larger samples and using other
      ethnicities are still needed to confirm our conclusion.

PMID- 29029460
TI  - VRK1 promotes cisplatin resistance by up-regulating c-MYC via c-Jun activation
      and serves as a therapeutic target in esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is a common malignant disease
      characterized by poor prognosis. Chemoresistance remains a major cause of ESCC
      relapse. Vaccinia-related kinase 1 (VRK1) has previously been identified as a
      cancer-related gene. However, there is little research demonstrating an
      association between VRK1 and ESCC. In this study, we show that VRK1 is
      overexpressed in ESCC primary tumor samples and cell lines. VRK1 expression was
      significantly correlated with clinical characteristics and predicted poor
      outcomes in ESCC patients. Functionally, knockdown of VRK1 inhibited ESCC cell
      proliferation, survival, migration and invasion; conversely, VRK1 overexpression
      produced the opposite effects. Furthermore, we found that up-regulation of VRK1
      promoted cisplatin (CDDP) resistance in ESCC both in vitro and in vivo, whereas
      knockdown of VRK1 reduced this resistance. Further studies verified that VRK1
      phosphorylated c-Jun and that the VRK1/c-Jun pathway contributed to CDDP
      resistance in ESCC. Mechanistically, a dual luciferase reporter assay revealed
      that c-Jun transcriptionally activated the expression of c-MYC. Silencing c-MYC
      abolished the c-Jun-mediated CDDP resistance of ESCC cells. A Kaplan-Meier
      analysis indicated that c-MYC is a potential prognostic factor in ESCC. Finally,
      luteolin, a VRK1 inhibitor, attenuated the malignant biological behaviors and
      CDDP resistance in ESCC cells. Collectively, we conclude that VRK1 promotes CDDP
      resistance through c-MYC by activating c-Jun and potentiating a malignant
      phenotype in ESCC. Our studies provide novel insight into the role of VRK1 in
      carcinogenesis and indicate that VRK1 can serve as a potential therapeutic target
      in ESCC.

PMID- 29029461
TI  - Prognostic value of long non-coding RNA TUG1 in various tumors.
AB  - Taurine up-regulated gene 1 (TUG1) is a long non-coding RNA (lncRNA), has been
      reported that be dysregulated in various tumors, involved in proliferation and
      apoptosis in a variety of tumor cells. To detect the clinical significance of
      TUG1 expression in tumor patients, we carried out current systematic review and
      meta-analysis investigating its relation with the prognosis and
      clinicopathological features of cancers. A total of 15 studies comprise 1560
      patients were analyzed. The pooled results showed that no significant
      relationship between high TUG1 expression and overall survival (OS) (HR = 1.28,
      95% CI: 0.96-1.69, P = 0.091) in various tumors. In the subgroup analysis by
      cancer type, elevated TUG1 expression was associated with poorer survival in
      cancer patients with high TUG1 expression subgroup but better survival in
      patients with low TUG1 expression subgroup. Over-expression of TUG1 associated
      with significantly unfavorable survival for bladder cancer (HR=2.67, 95% CI: 1.47
      4.87, P = 0.001). Up-regulation of TUG1 correlated with distant metastasis (DM)
      (OR = 4.22, 95% CI: 2.66-6.70, P < 0.001) and tumor differentiation (OR = 2.45,
      95% CI: 1.28-4.70, P = 0.007), but failed to show inline to gender (OR = 1.04,
      95% CI: 0.77-1.42, P = 0.774), age (OR = 0.75, 95% CI: 0.51-1.10, P = 0.136),
      lymph node metastasis (LNM) (OR = 1.45, 95% CI: 0.85-2.50, P = 0.177), and TNM
      stage (OR = 0.55, 95% CI: 0.17-1.81, P = 0.326). The overall results suggest
      lncRNA TUG1 may be a useful prognostic biomarker in cancer patients.

PMID- 29029459
TI  - Melatonin promotes the proliferation of GC-1 spg cells by inducing
      metallothionein-2 expression through ERK1/2 signaling pathway activation.
AB  - Synthesized by the pineal gland, melatonin is a neurohormone implicated in
      diverse physiological functions via several mechanisms. However, the role of
      melatonin in spermatogenesis and its underlying mechanisms have yet to be
      completely understood. In the present study, transcriptome sequencing was
      performed to characterize the mechanism of melatonin-induced GC-1 spg
      proliferation. Gene ontology (GO) enrichment and pathway analyses were also
      conducted to identify the signaling pathways and biological processes involved in
      differential mRNA expression. Results revealed 28 differential genes. Of these
      genes, 11 were upregulated and 17 were downregulated. Melatonin increased the
      expression of metallothionein-2 (Mt2), a gene that acts as a protector to
      sequester nonessential toxic heavy metals. Functional investigations demonstrated
      that Mt2 overexpression promoted the proliferation of GC-1 spg cells, but Mt2
      knockdown significantly suppressed their proliferation and increased their
      apoptosis. Mechanistic analysis indicated that the extracellular-signal-regulated
      kinase 1/2 (ERK1/2) pathway participated in melatonin-promoted proliferation of
      GC-1 spg cells. Therefore, melatonin induces the proliferation of GC-spg 1 cells
      by stimulating Mt2 expression, and this process is mediated by the ERK1/2
      signaling pathway.

PMID- 29029462
TI  - The appropriate number of ELNs for lymph node negative breast cancer patients
      underwent MRM: a population-based study.
AB  - Whether number of examed lymph nodes (ELNs) would bring survival benefit for
      patients with negative lymph nodes after modified radical mastectomy (MRM) is
      uncertain. In our study, using the Surveillance Epidemiology and End Results
      (SEER) database between 2004 and 2009, we screened the appropriate patients with
      negative lymph nodes underwent MRM. The Cox proportional hazard analysis was used
      to determine the effect of number of ELNs on cancer specific survival (CSS). The
      results showed that the number of ELNs was not an independent prognostic factor
      on CSS (P = 0.940). Then the X-tile mode was used to determine the appropriate
      threshold for ELNs count. The results showed that 9 was the appropriate cut-off
      point. Next, the log-rank chi2 test was used to analyze the CSS based on
      different subgroup variables. The results showed that some subgroup variables
      including age < 50/ >= 50, grade I/III, AJCC T1/T2, ER positive/negative and PR
      positive/negative ,demonstrated significant CSS benefits among the patients with
      the number of ELNs <= 9 (all, P < 0.05). However, three subgroup variables
      including grade II, AJCC T3 and AJCC T4, the patients with the number of ELNs <=
      9 did not bring significant CSS benefits (all, P > 0.1). In conclusion, our study
      demonstrated that the number of ELNs was not an independent prognostic factor on
      CSS, and 9 can be selected as the appropriate cut-off point of ELNs for patients
      with negative lymph nodes who underwent MRM.

PMID- 29029463
TI  - Cystathionine- gamma-lyase promotes process of breast cancer in association with
      STAT3 signaling pathway.
AB  - Here we provide evidences to link cystathionine-gamma-lyase (CSE) to the
      development of breast cancer. CSE expression is up-regulated in both breast
      cancers and breast cancer cell lines and results in proliferation and migration
      of breast cancer cells. CSE Function in breast cancer depends on the STAT3
      signaling pathway, a regulator of critical cell functions including cell growth
      in a wide variety of human cancer cells via activating the expression of relative
      genes. STAT3 positively relates to CSE expression. It activates the CSE promoter
      via a direct binding to the promoter. Moreover, CSE could reversely regulate
      STAT3 expression and consequently enhance the effect of STAT3 on CSE. Taken
      together, these data demonstrate for the first time the roles of CSE in breast
      cancer leading to breast cancer development in association with STAT3 signaling
      pathway.

PMID- 29029464
TI  - MiR-324-3p promotes tumor growth through targeting DACT1 and activation of
      Wnt/beta-catenin pathway in hepatocellular carcinoma.
AB  - Recently, it has been reported that miR-324-3p participates in regulation of the
      carcinogenesis and tumor progression in various cancers. However, the expression
      and function of miR-324-3p in hepatocellular carcinoma (HCC) remain unclear. In
      the current study, miR-324-3p expression was significantly up-regulated in HCC
      tissues and cell lines. HCC patients with high miR-324-3p level showed poor
      prognostic features and shorter overall survival and disease-free survival. And
      in vitro and in vivo experiments revealed that miR-324-3p promoted cell
      viability, colony formation, proliferation and cell cycle progression of HCC
      cells. Further studies demonstrated that miR-324-3p could directly target DACT1
      (dishevelled binding antagonist of beta catenin 1) and negatively regulated its
      expression in HCC cells. And rescue experiments revealed that DACT1 could reverse
      the effects of miR-324-3p on HCC cells. Furthermore, the accumulation of both
      cytoplasmic and nuclear beta-catenin as well as its downstream targets including
      c-Myc and cyclin D1 could be positively regulated by miR-324-3p. The regulatory
      effects of miR-324-3p on beta-catenin, c-Myc and cyclin D1 levels could be
      reversed by DACT1. Overall, we concluded that miR-324-3p could promote tumor
      growth through targeting DACT1 and activation of Wnt/beta-catenin pathway in HCC.
      MiR-324-3p may be a ponderable and promising therapeutic target for HCC.

PMID- 29029465
TI  - Alterations in DNA methylation/demethylation intermediates predict clinical
      outcome in chronic lymphocytic leukemia.
AB  - Cytosine derivative dysregulations represent important epigenetic modifications
      whose impact on the clinical outcome in chronic lymphocytic leukemia (CLL) is
      incompletely understood. Hence, global levels of 5-methylcytosine (5-mCyt), 5
      hydroxymethylcytosine (5-hmCyt), 5-carboxylcytosine (5-CaCyt) and 5
      hydroxymethyluracil were tested in purified B cells from CLL patients (n = 55)
      and controls (n = 17). The DNA methylation 'writers' (DNA methyltransferases
      [DNMT1/3A/3B]), 'readers' (methyl-CpG-binding domain [MBD2/4]), 'editors' (ten
      eleven translocation [TET1/2/3]) and 'modulators' (SAT1) were also evaluated.
      Accordingly, patients were stratified into three subgroups. First, a subgroup
      with a global deficit in cytosine derivatives characterized by
      hyperlymphocytosis, reduced median progression free survival (PFS = 52 months)
      and shorter treatment free survival (TFS = 112 months) was identified. In this
      subgroup, major epigenetic modifications were highlighted including a reduction
      of 5-mCyt, 5-hmCyt, 5-CaCyt associated with DNMT3A, MBD2/4 and TET1/2
      downregulation. Second, the cytosine derivative analysis revealed a subgroup with
      a partial deficit (PFS = 84, TFS = 120 months), mainly affecting DNA
      demethylation (5-hmCyt reduction, SAT1 induction). Third, a subgroup
      epigenetically similar to controls was identified (PFS and TFS > 120 months). The
      prognostic impact of stratifying CLL patients within three epigenetic subgroups
      was confirmed in a validation cohort. In conclusion, our results suggest that
      dysregulations of cytosine derivative regulators represent major events acquired
      during CLL progression and are independent from IGHV mutational status.

PMID- 29029466
TI  - A comparative study of anti-aging properties and mechanism: resveratrol and
      caloric restriction.
AB  - Resveratrol and caloric restriction (CR) are the powerful therapeutic options for
      anti-aging. Here, their comparative effect on longevity-associated gene silencing
      information regulator (SIRT1) were evaluated in vitro and in vivo. IMR-90 cells
      treated with 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) were applied
      to establish a cellular senescence model, and rats treated with D-galactose (D
      gal) were used as an aging animal model. Resveratrol and CR exhibited similar
      anti-aging activities, evidenced by inhibiting senescence and apoptosis, and
      restoring cognitive impairment and oxidative damage. Moreover, they could up
      regulate telomerase (TE) activity, increase expressions of SIRT1, forkhead box 3a
      (Foxo3a), active regulator of SIRT1 (AROS) and Hu antigen R (HuR ), but decrease
      p53 and deleted in breast cancer 1 (DBC1) levels. However, 10 MUM resveratrol in
      vitro and the high dose group in vivo showed relatively stronger activities of
      anti-aging and stimulating SIRT1 level than CR. In conclusion, resveratrol and CR
      showed similar anti-aging activities on SIRT1 signaling, implicating the
      potential of resveratrol as a CR mimetic.

PMID- 29029467
TI  - NHERF1 together with PARP1 and BRCA1 expression as a new potential biomarker to
      stratify breast cancer patients.
AB  - It has been recognized that Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) in
      breast cancer (BC) acts as a tumor suppressor or as an oncogenic protein,
      depending on its subcellular localization. This study aims to correlate NHERF1
      expression to BRCA1 and PARP1 proteins, to investigate their relationship, and
      their biological and clinical significance. Using immunohistochemistry on tissue
      microarrays, we evaluated subcellular NHERF1, BRCA1 and PARP1 expression in 308
      BCs including a subgroup (n=80) of triple negative BCs (TNBCs). Herein, we show
      that nuclear NHERF1 (nNHERF1) expression was significantly associated with
      nuclear BRCA1 (nBRCA1) expression (p=0.0008), and an association was also found
      between nuclear PARP1 (nPARP1) and nBRCA1 (p<0.0001). Cytoplasmic NHERF1
      (cNHERF1) was correlated to nPARP1 (p<0.0001). Survival analyses showed that the
      patients with positive nPARP1 and nNHERF1 tended toward a shorter 5-year overall
      survival (OS) (p=0.057). In TNBCs, the association between nBRCA1 and nPARP1 was
      maintained (p<0.0001), and an association between nNHERF1 and nPARP1 was observed
      (p=0.010). Univariate analysis revealed that TNBCs with positive cNHERF1 and
      nPARP1 had a shorter 5-year OS (p=0.048). Our data suggest that NHERF1 could be a
      new potential biomarker in combination with PARP1 and BRCA1 expression to
      stratify BC patients. In particular, in TNBCs, cNHERF1 associated with nPARP1
      expression identified a patient subgroup with a shorter survival, for whom it may
      be useful to develop novel therapeutic strategies.

PMID- 29029468
TI  - Resveratrol promotes MICA/B expression and natural killer cell lysis of breast
      cancer cells by suppressing c-Myc/miR-17 pathway.
AB  - Major histocompatibility complex class I chain-related proteins A and B (MICA and
      MICB) are important ligands for recognition of tumor cells by immune effector
      cells. Here, we report that resveratrol upregulated the protein and mRNA
      expression of MICA and MICB in breast cancer cells, which in turn promoted breast
      cancer cell lysis by natural killer (NK) cells in vitro and in vivo. Antibodies
      against NK group 2 member D blocked this effect. The 3'-untranslated regions of
      MICA and MICB were found to be direct binding targets of miR-17. MICA and MICB
      expression increased or decreased in breast cancer cells transfected with a miR
      17 inhibitor or mimic, respectively. C-Myc overexpression/knockdown
      increased/decreased transcription of the miR-17-92 cluster host gene. Resveratrol
      suppressed c-Myc expression, which inhibited the transcription of miR-17-92
      cluster, thereby downregulating miR-17. MiR-17 expression correlated inversely
      with MICA and MICB expression and overall survival in two sets of breast cancer
      specimens. Resveratrol thus upregulates MICA and MICB by suppressing the c
      Myc/miR-17 pathway in breast cancer cells, and increases the cytolysis of breast
      cancer cells by NK cells. This suggests resveratrol has the potential to promote
      antitumor immune responses in breast cancer patients.

PMID- 29029469
TI  - Genetic and environmental factors and serum hormones, and risk of estrogen
      receptor-positive breast cancer in pre- and postmenopausal Japanese women.
AB  - Breast cancer incidence in Japanese women has more than tripled over the past two
      decades. We have previously shown that this marked increase is mostly due to an
      increase in the estrogen receptor (ER)-positive, HER2-negative subtype. We
      conducted a case-control study; ER-positive, HER2-negative breast cancer patients
      who were diagnosed since 2011 and women without disease were recruited.
      Environmental factors, serum levels of testosterone and 25-hydroxyvitamin D, and
      common genetic variants reported as predictors of ER-positive breast cancer or
      found in Asian women were evaluated between patients and controls in pre- and
      postmenopausal women. To identify important risk predictors, risk prediction
      models were created by logistic regression models. In premenopausal women, two
      environmental factors (history of breastfeeding, and history of benign breast
      disease) and four genetic variants (TOX3-rs3803662, ESR1-rs2046210, 8q24
      rs13281615, and SLC4A7-rs4973768) were considered to be risk predictors, whereas
      three environmental factors (body mass index, history of breastfeeding, and
      hyperlipidemia), serum levels of testosterone and 25-hydroxyvitamin D, and two
      genetic variants (TOX3-rs3803662 and ESR1-rs2046210) were identified as risk
      predictors. Inclusion of common genetic variants and serum hormone measurements
      as well as environmental factors improved risk assessment models. The decline in
      the birthrate according to recent changes of lifestyle might be the main cause of
      the recent notable increase in the incidence of ER-positive breast cancer in
      Japanese women.

PMID- 29029470
TI  - Real-time in vivo imaging of metastatic bone tumors with a targeted near-infrared
      fluorophore.
AB  - Tumors of the prostate or breast are particularly likely to metastasize to the
      bone, and early diagnosis of metastatic bone tumors is important for designing an
      effective treatment strategy. Imaging modalities for the detection of bone
      metastasis are limited, and radiation-based techniques are commonly used. Here,
      we investigated the efficacy of selective near-infrared (NIR) fluorescence
      detection of metastatic bone tumors and its role in the detection of bone
      metastasis in prostate and breast cancer cell lines and in a xenograft mouse
      model. A targeted NIR fluorophore was used to monitor metastatic bone tumors
      using a NIR fluorescence imaging system in real time, enabling the diagnosis of
      bone metastasis in vivo by providing the location of the metastatic bone tumor.
      The NIR fluorescence imaging technique using targeted NIR contrast agents is a
      potential tool for the early diagnosis of bone tumors.

PMID- 29029471
TI  - Protective effect of resveratrol against light-induced retinal degeneration in
      aged SAMP8 mice.
AB  - PURPOSE: The purpose of this study was to determine the protective effects of
      Resveratrol (RESV) on acute bright light-induced retinal degeneration in aged
      senescence accelerated mouse strain. METHODS: Ten three-month-old male SAMP8 mice
      (prone to aging) were randomly assigned to two experimental dietary groups: one
      untreated group and one RESV treatment group (n=20 eyes for each group). After 30
      days of treatment, mice were exposed to intense bright light. Ten male SAMR1 mice
      (resistant to aging) served as control (n=20 eyes). The protective effects of
      RESV administration on light-induced retinal degeneration in SAMP8 strain as well
      as the effect of bright light damage in the retinas of SAMP8 mice were analyzed
      by electroretinography (ERG), retinal histology, mRNA, protein and lipid profile.
      RESULTS: 68%-85% of a-wave amplitude and 72%-92% of b-wave amplitude were
      persevered by RESV in SAMP8 mice that were exposed to light damage. Also, RESV
      preserved their photoreceptor nuclei. mRNA expression of neuroprotective factors
      leukemia inhibitory factor (LIF), brain derived neurotrophic factor (BDNF),
      oncostatin M (OSM), cardiotrophin 1(CT-1) and cardiotrophin-like cytokine (CLC)
      were up-regulated 28, 8, 7, 5 and 9-fold in SAMP8 mice after RESV treatment. In
      addition, RESV could suppress the NF-kappaB pathway by down-regulating the
      expression of pIkappaB. Light damage led to increase of saturated FA, monoenoic
      FA, n6 PUFA and n6/n3 ratio and decrease of Docosahexaenoic acid (DHA). There was
      no significant difference on DHA and the ratio of n6/n3-FA between the untreated
      and RESV treated SAMP8 mice. CONCLUSIONS: Collectively, our study provides
      evidence that RESV prevents light-induced retinal damage associated with aging.

PMID- 29029472
TI  - Up-regulation of brain-expressed X-linked 2 is critical for hepatitis B virus X
      protein-induced hepatocellular carcinoma development.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death
      worldwide. Chronic hepatitis B virus (HBV) infection is a major cause for HCC.
      Hepatitis B virus X (HBx), one of four proteins encoded by HBV genome, plays a
      vital role in the pathogenesis of HBV-induced HCC. However, the molecular
      mechanisms of HBx-triggered HCC remain largely undetermined. Here we revealed
      that the expression of Brain-expressed X-linked 2 (BEX2) and Osteopontin (OPN)
      were elevated in liver tissues of HBV transgenic mice and human HCC specimens.
      Moreover, a positive correlation between BEX2 and OPN was exhibited in samples
      from HCC patients with HBV infection. The protein levels of BEX2 and OPN were
      both higher in HBV-positive HCC specimens compared to that of HBV-negative HCC
      specimens. HBx potentiated OPN expression through up-regulation of BEX2.
      Importantly, the depletion of BEX2 suppressed tumorigenic potential of HCC cells
      with highly expressed HBx. We demonstrated the important role of BEX2 in HCC
      pathogenesis, and BEX2 may be a novel therapeutic target for HCC patients with
      HBV infection. The newly identified HBx/BEX2/OPN signaling cassette is implicated
      in the pathogenesis of HBV-induced HCC.

PMID- 29029473
TI  - NBPF7 promotes the proliferation of alpha-catenin-knockdown HaCaT cells via
      functional interaction with the NF-kappaB pathway.
AB  - Loss of key components that form cell-cell adherens junctions, such as alpha
      catenin, triggers severe epidermal hyperproliferation. However, the underlying
      molecular mechanisms remain largely unknown. We report here that neuroblastoma
      breakpoint family (NBPF) genes are upregulated and that NBPF7 specifically
      promotes cellular proliferation of alpha-catenin-silenced HaCaT cells through
      functional linkage with the NF-kappaB pathway. Genome-wide profiling of HaCaT
      cells shows that NBPF genes are upregulated following alpha-catenin knockdown.
      Data from western blot analyses are consistent with the activation of the NF
      kappaB pathway as well as increased expression of NBPF7 by alpha-catenin
      knockdown. Co-immunoprecipitation assays indicate that NBPF7 could be detected in
      endogenous activated NF-kappaB immunoprecipitates. Immunoflurence analyses
      demonstrate that NBPF7 co-localizes with activated NF-kappaB in the nucleus after
      alpha-catenin silencing. Moreover, inhibition of NBPF7 decreases the
      proliferation of HaCaT cells and abolishes the enhanced proliferation associated
      with alpha-catenin knockdown in HaCaT cells. These results indicate that NBPF7
      plays a key role in the alpha-catenin signaling pathway that regulates cell
      proliferation of keratinocytes. Our findings suggest that the classical NF-kappaB
      pathway plays a critical role in cellular proliferation and that NBPF7 is a
      functional mediator for alpha-catenin in the regulation of keratinocyte growth.

PMID- 29029474
TI  - Regulatory actions of ToxR and CalR on their own genes and type III secretion
      system 1 in Vibrio parahaemolyticus.
AB  - Vibrio parahaemolyticus is the leading cause of seafood-associated
      gastroenteritis. Type III secretion system 1 (T3SS1) is one of the virulence
      determinants of this bacteria. T3SS1 expression is regulated by ToxR and CalR.
      ToxR represses the transcription of T3SS1 genes via activation of CalR, which
      acts as a transcriptional repressor of T3SS1 genes. However, the transcriptional
      regulation mechanisms have not been elucidated. As showing in the present work,
      ToxR binds to the promoter DNA region of calR to activate its transcription. CalR
      occupies the promoter-proximal regions of each detected target operons in T3SS1
      loci to repress their transcription, and thereby inhibiting T3SS1-dependent
      cytotoxicity. Moreover, a feedback CalR inhibits toxR and its own gene in a
      direct manner. Collectively, this work reported an interesting gene regulatory
      network involving the reciprocal regulation of ToxR and CalR, and their
      regulation on T3SS1 genes transcription in V. parahaemolyticus.

PMID- 29029475
TI  - The prognostic potential and carcinogenesis of long non-coding RNA TUG1 in human
      cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is a fatal disease with increasing worldwide incidence
      and is characterized by poor prognosis due to its poor response to conventional
      chemotherapy or radiotherapy. Long non-coding RNAs (lncRNAs) play key roles in
      multiple human cancers, including CCA. Cancer progression related lncRNA taurine
      up-regulated gene 1 (TUG1) was reported to be involved in human carcinomas.
      However, the impact of TUG1 in CCA is unclear. The aim of this study was to
      explore the expression pattern of TUG1 and evaluate its clinical significance as
      well as prognostic potential in CCA. In addition, the functional roles of TUG1
      including cell proliferation, apoptosis, migration, invasion and epithelial
      mesenchymal transition (EMT), were evaluated after TUG1 silencing. Our data
      demonstrated up-regulation of TUG1 in both CCA tissues and cell lines. Moreover,
      overexpression of TUG1 is linked to tumor size (p=0.005), TNM stage (p=0.013),
      postoperative recurrence (p=0.036) and overall survival (p=0.010) of CCA
      patients. Furthermore, down-regulation of TUG1 following RNA silencing reduced
      cell growth and increased apoptosis in CCA cells. Additionally, TUG1 suppression
      inhibited metastasis potential in vitro by reversing EMT. Overall, our results
      suggest that TUG1 may be a rational CCA-related prognostic factor and therapeutic
      target.

PMID- 29029476
TI  - Contrastive study of two screening criteria for active surveillance in patients
      with low-risk papillary thyroid microcarcinoma: a retrospective analysis of 1001
      patients.
AB  - Screening out patients who do not require immediate surgery is a growing trend in
      the field of thyroid research. In this study, we retrospectively compared the
      application of two surveillance selection criteria in 1001 patients who had
      undergone surgical treatment of papillary thyroid microcarcinoma (PTMC): low-risk
      PTMC characteristics defined by Kuma Hospital and CATO consensus on PTMC
      management of active surveillance. Treatment outcomes were compared between
      groups. We then analyzed the prognostic indicators of patients who could be
      managed by surveillance. A total of 724 patients met Kuma screening criteria and
      135 met CATO screening criteria. The Kuma low-risk group had a lower incidence of
      multifocal lesions and CLNM than Kuma high-risk group. We also found more obvious
      differences in multifocal lesions, CLNM and extrathyroidal extension when
      evaluating the CATO low-risk criteria in the same manner. On the other hand,
      patients in the CATO low-risk group had a lower disease progression rate and
      longer disease-free survival than those in CATO high-risk group. There was no
      significant difference in prognosis between the Kuma low-risk group and Kuma high
      risk group. Our logistic regression analysis showed that a preoperative
      ultrasound size of >5 mm, male sex, younger age, and malignant lesions without
      concurrent benign nodules could be predictors of CLNM. In conclusion, patients
      classified in CATO low-risk criteria had lower proportion of clinicopathological
      risk factors than the ones in Kuma low-risk criteria. We also found more risk
      factors may not be suitable for surveillance, such as tumors without concurrent
      benign nodules.

PMID- 29029477
TI  - Coexpression analysis identifies nuclear reprogramming barriers of somatic cell
      nuclear transfer embryos.
AB  - The success of cloned animal "Dolly Sheep" demonstrated the somatic cell nuclear
      transfer (SCNT) technique holds huge potentials for mammalian asexual
      reproduction. However, the extremely poor development of SCNT embryos indicates
      their molecular mechanism remain largely unexplored. Deciphering the
      spatiotemporal patterns of gene expression in SCNT embryos is a crucial step
      toward understanding the mechanisms associated with nuclear reprogramming. In
      this study, a valuable transcriptome recourse of SCNT embryos was firstly
      established, which derived from different inter-/intra donor cells. The gene co
      expression analysis identified 26 cell-specific modules, and a series of
      regulatory pathways related to reprogramming barriers were further enriched.
      Compared to the intra-SCNT embryos, the inter-SCNT embryos underwent only
      complete partially reprogramming. As master genome trigger genes, the transcripts
      related to TFIID subunit, RNA polymerase and mediators were incomplete activated
      in inter-SCNT embryos. The inter-SCNT embryos only wasted the stored maternal
      mRNA of master regulators, but failed to activate their self-sustained pathway of
      RNA polymerases. The KDM family of epigenetic regulator also seriously delayed in
      inter-SCNT embryo reprogramming process. Our study provided new insight into
      understanding of the mechanisms of nuclear reprogramming.

PMID- 29029478
TI  - Effects of exercise on capillaries in the white matter of transgenic AD mice.
AB  - Previous studies have shown that exercise can prevent white matter atrophy in
      APP/PS1 transgenic Alzheimer's disease (AD) mice. However, the mechanism of this
      protective effect remains unknown. To further understand this issue, we
      investigated the effects of exercise on the blood supply of white matter in
      transgenic AD mice. Six-month-old male APP/PS1 mice were randomly divided into a
      control group and a running group, and age-matched non-transgenic littermates
      were used as a wild-type control group. Mice in the running group ran on a
      treadmill at low intensity for four months. Then, spatial learning and memory
      abilities, white matter and white matter capillaries were examined in all mice.
      The 10-month-old AD mice exhibited deficits in cognitive function, and 4 months
      of exercise improved these deficits. The white matter volume and the total
      length, total volume and total surface area of the white matter capillaries were
      decreased in the 10-month-old AD mice, and 4 months of exercise dramatically
      delayed the changes in these parameters in the AD mice. Our results demonstrate
      that even low-intensity running exercise can improve spatial learning and memory
      abilities, delay white matter atrophy and protect white matter capillaries in
      early-stage AD mice. Protecting capillaries might be an important structural
      basis for the exercise-induced protection of the structural integrity of white
      matter in AD.

PMID- 29029479
TI  - The genetically engineered drug rhCNB induces apoptosis via a mitochondrial route
      in tumor cells.
AB  - The calcineurin B subunit (CNB) has antitumor activity. We showed previously that
      recombinant human CNB (rhCNB) also had strong anti-tumor activity in vivo, and
      was thus a promising candidate anti-tumor drug. It appeared to kill tumor cells
      via immunomodulation. Here, we show that rhCNB inhibits the proliferation of
      human hepatoma HepG-2 cells, resulting in their apoptosis. Exogenous CNB was
      found to localize to mitochondria in tumor cells and activate the mitochondrial
      apoptosis pathway, as indicated by a decrease of mitochondrial transmembrane
      potential, release of cytochrome C and activation of caspase-9, which then
      activates caspase-3. At the same time Bcl-2 &Bcl-xL expression decreased, Bim
      expression increased, and Bax was activated. Interaction between rhCNB and Bcl-xL
      was detected, which may inhibit the function of Bcl-xL. Long-term tumor targeting
      was also observed in nude mice. These data deepened our understanding of the anti
      tumor mechanism of rhCNB and provided guidance for its drug development.

PMID- 29029480
TI  - Small molecule CP-31398 induces reactive oxygen species-dependent apoptosis in
      human multiple myeloma.
AB  - Reactive oxygen species (ROS) are normal byproducts of a wide variety of cellular
      processes. ROS have dual functional roles in cancer cell pathophysiology. At low
      to moderate levels, ROS act as signaling transducers to activate cell
      proliferation, migration, invasion, and angiogenesis. In contrast, high levels of
      ROS induce cell death. In multiple myeloma (MM), ROS overproduction is the
      trigger for apoptosis induced by several anticancer compounds, including
      proteasome inhibitors. However, no drugs for which oxidative stress is the main
      mechanism of action are currently used for treatment of MM in clinical
      situations. In this study, we demonstrate that the p53-activating small molecule
      CP-31398 (CP) effectively inhibits the growth of MM cell lines and primary MM
      isolates from patients. CP also suppresses the growth of MM xenografts in mice.
      Mechanistically, CP was found to induce intrinsic apoptosis in MM cells via
      increasing ROS production. Interestingly, CP-induced apoptosis occurs regardless
      of the p53 status, suggesting that CP has additional mechanisms of action. Our
      findings thus indicate that CP could be an attractive candidate for treatment of
      MM patients harboring p53 abnormalities; this satisfies an unmet clinical need,
      as such individuals currently have a poor prognosis.

PMID- 29029481
TI  - Cell cycle specific radiosensitisation by the disulfiram and copper complex.
AB  - The disulfiram and copper complex (DSF:Cu) has emerged as a potent
      radiosensitising anti-cancer agent. The ability of copper to stabilise DSF in a
      planar conformation and to inhibit DNA replication enzymes stimulated our
      investigation of the effect of DSF:Cu on cell cycle regulation. Flow cytometry
      and immunoblotting were used to assess the effect of DSF:Cu on cell cycle
      progression of the neuroblastoma cell line SK-N-BE(2c) and the glioma cell line
      UVW. Treatment with 0.1 and 0.3 MUM DSF:Cu inhibited DNA synthesis in SK-N-BE(2c)
      and UVW cells, respectively. The increased potency of ionising radiation
      treatment induced by DSF:Cu and/or gemcitabine was determined by clonogenic
      assay. Treatment with 0.3 MUM DSF:Cu resulted in greater radiation kill,
      exemplified by dose enhancement factor values of 2.64 and 2.84 in SK-N-BE(2c) and
      UVW cells, respectively. Although DSF:Cu failed to sensitise S phase cells to
      irradiation, we observed that DSF:Cu radiosensitisation was potentiated by the S
      phase-specific cytotoxic drug gemcitabine. The efficacy of the combination
      treatment consisting of DSF:Cu, gemcitabine and ionising radiation was schedule
      dependent. Together, these results describe cell cycle specific
      radiosensitisation by DSF:Cu. The well-established toxicity profiles of DSF and
      gemcitabine should facilitate their evaluation as a combination treatment in
      patients undergoing radiotherapy.

PMID- 29029482
TI  - In vivo immuno-targeting of an extracellular epitope of membrane bound
      preferentially expressed antigen in melanoma (PRAME).
AB  - Preferentially Expressed Antigen in Melanoma (PRAME) is a cancer/testis antigen
      that is overexpressed in a broad range of malignancies, while absent in most
      healthy human tissues, making it an attractive diagnostic cancer biomarker and
      therapeutic target. Although commonly viewed as an intracellular protein, we have
      demonstrated that PRAME has a membrane bound form with an external epitope
      targetable with conventional antibodies. We generated a polyclonal antibody
      (Membrane associated PRAME Antibody 1, MPA1) against an extracellular peptide
      sequence of PRAME. Binding of MPA1 to recombinant PRAME was evaluated by Enzyme
      Linked Immunosorbent Assay (ELISA). Flow cytometry and confocal
      immunofluorescence microscopy of MPA1 was performed on multiple tumor cell lines.
      Reverse Transcription Polymerase Chain Reaction (RT-PCR) for PRAME was conducted
      to compare protein and transcriptional expression levels. We demonstrated a
      robust proof-of-concept for PRAME targeting in vivo by radiolabeling MPA1 with
      zirconium-89 (89Zr-DFO-MPA1) and demonstrating high specific uptake in PRAME
      expressing tumors. To our knowledge, this is the first time a cancer testis
      antigen has been targeted using conventional antibody technologies. Thus, PRAME
      can be exploited for multiple clinical applications, including targeted therapy,
      diagnostic imaging and treatment guidance in a wide-range of malignancies, with
      minimal off-target toxicity.

PMID- 29029484
TI  - YBX1 promotes tumor growth by elevating glycolysis in human bladder cancer.
AB  - Aerobic glycolysis, also known as Warburg effect, is a key hallmark of cancers.
      The Y-box-binding protein 1 (YBX1) is a well-known oncoprotein implicated in
      multiple malignant phenotypes of cancers. Meanwhile, little is known about the
      oncogenic functions and mechanisms of YBX1 in bladder cancer. Based on gene set
      enrichment analysis (GSEA) of TCGA RNAseq data, we find that YBX1 was profoundly
      involved in the glycolysis part of glucose metabolism. Loss- and gain-of-function
      studies show that YBX1 can enhance glycolysis as revealed by expression of
      glycolytic enzymes, glucose uptake, lactate secretion and extracellular
      acidification rate (ECAR). Inhibition of glycolysis completely compromises the
      tumor-promoting effect of YBX1 on tumor growth. Mechanistically, YBX1 regulates
      the expression of c-Myc and HIF1alpha, which further upregulate glycolytic
      enzymes to facilitate glycolysis. Moreover, in vivo study further confirms that
      genetic silencing of YBX1 markedly attenuates tumor growth and this tumor
      suppressive effect is largely dependent on reduced glycolysis. Taken together,
      these results, as a proof of principle, provide a novel insight into the
      oncogenic role of YBX1 in glycolysis and suggest the potential therapeutic
      strategy by targeting YBX1 in bladder cancer.

PMID- 29029483
TI  - The long noncoding RNA TUG1 acts as a competing endogenous RNA to regulate the
      Hedgehog pathway by targeting miR-132 in hepatocellular carcinoma.
AB  - Emerging evidence shows that the Hedgehog pathway and the long noncoding RNA TUG1
      play pivotal roles in cell proliferation, migration, and invasion in tumors.
      However, the mechanism underlying the effect of TUG1 and the Hedgehog pathway in
      hepatoma remains undefined. In the present study, we showed that the expression
      of TUG1 was negatively correlated with that of microRNA (miR)-132, and depletion
      of TUG1 inhibited the activation of the Hedgehog pathway in vitro and in vivo. We
      showed that TUG1 functions as a competing endogenous (ceRNA) by competing with
      miR-132 for binding to the sonic hedgehog protein in HCC, thereby suppressing the
      activation of Hedgehog signaling and its tumorigenic effect. These data indicate
      that targeting the TUG1-miR132-Hedgehog network could be a new strategy for the
      treatment of HCC.

PMID- 29029485
TI  - FZD7 is a novel prognostic marker and promotes tumor metastasis via WNT and EMT
      signaling pathways in esophageal squamous cell carcinoma.
AB  - Frizzled (FZD) proteins are receptors for secreted WNT proteins and play a
      critical role in the malignant progression of various cancers. However, the role
      of human FZD family members in esophageal squamous cell carcinoma (ESCC) was
      rarely investigated. In this study, we found that the FZD7 gene was the most
      commonly up-regulated FZD member in ESCC cell lines compared with other FZDs. TMA
      studies further validated that FZD7 protein was up-regulated in 165 of 252
      (65.5%) informative ESCC patients and significantly correlated with poor overall
      survival (P=0.001). Additionally, multivariate Cox regression analysis showed
      that FZD7 overexpression was an independent prognostic factor for ESCC patients.
      Ectopic expression of FZD7 could promote ESCC cell metastasis both in vitro and
      in vivo. Under WNT3A stimulation, FZD7 was able to induce the nuclear
      translocation of beta-catenin and activate the downstream targets of WNT/beta
      catenin signaling, as well as promote epithelial-mesenchymal transition (EMT)
      potential in ESCC cells. Our study demonstrated for the first time that FZD7
      contributes to the malignant progression of ESCC and represents a novel
      prognostic marker and a potential therapeutic target for ESCC patients.

PMID- 29029486
TI  - EGF stimulates glioblastoma metastasis by induction of matrix metalloproteinase-9
      in an EGFR-dependent mechanism.
AB  - Epidermal growth factor (EGF) and EGF receptor (EGFR) play prominent roles in the
      metastasis of glioblastoma (GBM). However, the molecular mechanisms for the
      function of EGF and EGFR in GBM metastasis have not been elucidated. Herein, we
      demonstrate that coactivation of EGF and EGFR drives tumor metastasis in a matrix
      metalloproteinase-9 (MMP-9)-dependent manner. Expression levels of EGF, EGFR, and
      MMP-9 were substantially upregulated in the GBM and edema zones of patients,
      compared with those of paired unaffected participants. Secretion of EGF and MMP-9
      was reduced in the cerebrospinal fluid (CSF) after removing GBM for 2 weeks by
      operation. To the mechanism, MMP-9 was upregulated by activating EGF and EGFR via
      PI3K/AKT- and ERK1/2-dependent pathways. Moreover, signal transducer and
      activator of transcription (STAT) 3 and STAT5 mediated the activation of NF
      kappaB by PI3K/AKT and ERK1/2 pathways. This resulted in transactivation of MMP-9
      in GBM. Finally, MMP-9 induction facilitated abnormal proliferation, migration,
      and invasion of cells, which contributed to GBM metastasis.

PMID- 29029487
TI  - Prognostic factors and outcomes of primary transitional cell carcinoma of the
      ureter: a population-based study.
AB  - OBJECTIVE: This study investigated the prognostic factors and outcomes of a large
      observational cohort of patients with primary transitional cell carcinoma of the
      ureter, which was obtained from the Surveillance, Epidemiology, and End Results
      database. METHODS: We used the Surveillance, Epidemiology, and End Results
      program to identify 1910 patients who had available clinical and follow-up
      information and were diagnosed for primary transitional cell carcinoma of the
      ureter between 2004 and 2013. Descriptive statistics were used to explore the
      epidemiology, treatment practices, and tumor characteristics of the patients.
      Univariate and multivariable Cox regression models were used to analyze the
      patient data. RESULTS: The median overall survival (OS) was 46 months, and the 5
      year OS rate was 41.8%. The median CSS was 78 months, and the 5-year CSS rate was
      54.3%. Multivariate analysis identified tumor grade, tumor size, AJCC stage, M
      stage, cancer-directed surgical procedure and radiation as independent factors of
      primary transitional cell carcinoma of the ureter. For early stage patients, the
      surgical procedure was associated with fairly longer survival and additional
      radiation may cause more harm than benefit. Meanwhile, for advanced stage
      patients, the impact of surgery on OS and CSS greatly decreased. Radiation
      exerted a very limited impact on clinical outcomes. Patients with bad tumor
      differentiation or a large tumor size were more likely to have advanced stage
      disease. CONCLUSION: Durable cancer control can be expected in patients treated
      with surgery for early stage UTUC. The presence of advanced stage disease exerts
      a profound detrimental effect on the survival of patients.

PMID- 29029488
TI  - Integrated analysis of competing endogenous RNA network revealing lncRNAs as
      potential prognostic biomarkers in human lung squamous cell carcinoma.
AB  - Accumulating evidence shows the important role of long non-coding RNAs (lncRNAs)
      in competing endogenous RNA (ceRNA) networks for predicting survival in tumor
      patients. However, prognostic biomarkers for lung squamous cell carcinoma (LUSC)
      are still lacking. The objective of this study is to identify a lncRNA signature
      for evaluation of overall survival (OS) in 474 LUSC patients from The Cancer
      Genome Atlas (TCGA) database. A total of 474 RNA sequencing profiles in LUSC
      patients with clinical data were obtained, providing a large sample of RNA
      sequencing data, and 83 LUSC-specific lncRNAs, 26 miRNAs, and 85 mRNAs were
      identified to construct the ceRNA network (fold change>2, P<0.05). Among these
      above 83 LUSC-specific lncRNAs, 22 were assessed as closely related to OS in LUSC
      patients using a univariate Cox proportional regression model. Meanwhile, two
      (FMO6P and PRR26) of the above 22 OS-related lncRNAs were identified using a
      multivariate Cox regression model to construct a risk score as an independent
      indicator of the prognostic value of the lncRNA signature in LUSC patients. LUSC
      patients with low-risk scores were more positively correlated with OS (P<0.001).
      The present study provides a deeper understanding of the lncRNA-related ceRNA
      network in LUSC and suggests that the two-lncRNA signature could serve as an
      independent biomarker for prognosis of LUSC.

PMID- 29029489
TI  - Similar response profile to neoadjuvant chemotherapy, but different survival, in
      inflammatory versus locally advanced breast cancers.
AB  - : Inflammatory breast cancer (IBC) is a very aggressive form of breast cancer, as
      compared to locally advanced breast cancer (LABC). Neoadjuvant chemotherapy
      followed by surgery is the standard treatment in both cases. Whether IBC is less
      chemosensitive than LABC remains unclear. We retrospectively compared the rate of
      pathological complete response (pCR) to neoadjuvant chemotherapy in IBC and LABC.
      METHODS: Patients with IBC or LABC treated with neoadjuvant anthracycline-based
      chemotherapy followed by surgery were selected from our institutional database.
      The primary endpoint was the pCR rate, defined as absence of invasive tumor in
      breast and axillary lymph nodes. RESULTS: A total of 450 patients were included,
      144 with IBC and 306 with LABC. The pCR rate was similar between the two groups,
      in the whole population (31%) and in each molecular subtype separately.
      Univariate analyses for pCR in IBC and LABC separately identified the same
      predictive variables, except the pathological type that was associated with pCR
      in LABC only, but not in IBC. IBC patients displayed shorter 5-year metastasis
      free survival and overall survival than LABC patients in the whole population
      (57% and 69% versus74% and 88% respectively), and in each molecular subtype
      separately. The IBC phenotype was an independent prognostic feature. Similarly,
      IBC patients displayed shorter 5-year loco-regional relapse-free survival than
      LABC patients (86% versus 95%). CONCLUSIONS: Similar pCR rates to chemotherapy
      were found in IBC and LABC, suggesting that IBC is not less chemosensitive than
      LABC. Survival was shorter in IBC, suggesting that the corresponding poorer
      prognosis is more due to a higher metastatic risk and/or other feature(s) than to
      a lesser chemosensitivity.

PMID- 29029490
TI  - 7-ketocholesterol and 27-hydroxycholesterol decreased doxorubicin sensitivity in
      breast cancer cells: estrogenic activity and mTOR pathway.
AB  - Hypercholesterolemia is one of the risk factors for poor outcome in breast cancer
      therapy. To elucidate the influence of the main circulating oxysterols,
      cholesterol oxidation products, on the cell-killing effect of doxorubicin, cells
      were exposed to oxysterols at a subtoxic concentration. When cells were exposed
      to oxysterols in fetal bovine serum-supplemented medium, 7-ketocholesterol (7
      KC), but not 27-hydroxycholesterol (27-HC), decreased the cytotoxicity of
      doxorubicin in MCF-7 (high estrogen receptor (ER)alpha/ERbeta ratio) cells and
      the decreased cytotoxicity was restored by the P-glycoprotein inhibitor
      verapamil. 7-KC stimulated the efflux function of P-glycoprotein and reduced
      intracellular doxorubicin accumulation in MCF-7 but not in ERalpha(-) MDA-MB-231
      and the resistant MCF-7/ADR cells. In MCF-7 cells, 7-KC increased the mRNA and
      protein levels of P-glycoprotein. The 7-KC-suppressed doxorubicin accumulation
      was restored by the fluvestrant and ERalpha knockdown. In a yeast reporter assay,
      the ERalpha activation by 7-KC was more potent than 27-HC. 7-KC, but not 27-HC,
      stimulated the expression of an ER target, Trefoil factor 1 in MCF-7 cells. When
      charcoal-stripped fetal bovine serum was used, both 7-KC and 27-HC induced
      Trefoil factor 1 expression and reduced doxorubicin accumulation in MCF-7 cells.
      7-KC-reduced doxorubicin accumulation could be reversed by inhibitors of
      phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin (mTOR).
      These findings demonstrate that 7-KC decreases the cytotoxicity of doxorubicin
      through the up-regulation of P-glycoprotein in an ERalpha- and mTOR-dependent
      pathway. The 7-KC- and 27-HC-elicited estrogenic effects are crucial in the P
      glycoprotein induction in breast cancer cells.

PMID- 29029491
TI  - BMI and serum lipid parameters predict increasing risk and aggressive prostate
      cancer in Chinese people.
AB  - OBJECTIVES: To determine if obesity and serum lipid parameters are associated
      with increased risk and more aggressive prostate cancer in Chinese population.
      MATERIALS AND METHODS: We conducted a retrospective cohort analysis including
      3102 patients. Kruskal-Wallis test for continuous variables and the chi-squared
      tests for categorical variables were used for univariate comparison of the
      differences in patient characteristics across BMI categories between different
      groups. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for the
      association between prostate cancer and the various patient characteristics.
      Multivariable Cox proportional hazards regression was performed to assess the
      risk of prostate cancer recurrence. RESULTS: 974 consecutive men were diagnosed
      as prostate cancer and 700 patients subsequently received radical prostatectomy
      immediately, and 1031 patients were pathologically diagnosed as biopsy negative.
      The level of low-density-lipoprotein cholesterol (LDL-c) and total cholesterol
      was significantly higher and the high-density-lipoprotein cholesterol (HDL-c)
      level is much lower in prostate cancer patients. Patients with low level of HDL
      c, who subsequently received radical prostatectomy, had increased risk of high
      risk disease. In addition, patients with normal weight were less likely to
      develop a biochemical recurrence. Combined analysis revealed that obese patients
      had significantly higher rates of PSA recurrence over time than nonobese
      patients. CONCLUSIONS: In our study, lipid parameters are supposed to be
      associated with prostate cancer risk and aggressiveness. Obese men are at
      increased risk of PSA recurrence after radical prostatectomy.

PMID- 29029492
TI  - GATA2 regulates the erythropoietin receptor in t(12;21) ALL.
AB  - The t(12;21) (p13;q22) chromosomal translocation resulting in the ETV6/RUNX1
      fusion gene is the most frequent structural cytogenetic abnormality in children
      with acute lymphoblastic leukemia (ALL). The erythropoietin receptor (EPOR),
      usually associated with erythroid progenitor cells, is highly expressed in
      ETV6/RUNX1 positive cases compared to other B-lineage ALL subtypes. Gene
      expression analysis of a microarray database and direct quantitative analysis of
      patient samples revealed strong correlation between EPOR and GATA2 expression in
      ALL, and higher expression of GATA2 in t(12;21) patients. The mechanism of EPOR
      regulation was mainly investigated using two B-ALL cell lines: REH, which harbor
      and express the ETV6/RUNX1 fusion gene; and NALM-6, which do not. Expression of
      EPOR was increased in REH cells compared to NALM-6 cells. Moreover, of the six
      GATA family members only GATA2 was differentially expressed with substantially
      higher levels present in REH cells. GATA2 was shown to bind to the EPOR 5'-UTR in
      REH, but did not bind in NALM-6 cells. Overexpression of GATA2 led to an increase
      in EPOR expression in REH cells only, indicating that GATA2 regulates EPOR but is
      dependent on the cellular context. Both EPOR and GATA2 are hypomethylated and
      associated with increased mRNA expression in REH compared to NALM-6 cells.
      Decitabine treatment effectively reduced methylation of CpG sites in the GATA2
      promoter leading to increased GATA2 expression in both cell lines. Although
      Decitabine also reduced an already low level of methylation of the EPOR in NALM-6
      cells there was no increase in EPOR expression. Furthermore, EPOR and GATA2 are
      regulated post-transcriptionally by miR-362 and miR-650, respectively. Overall
      our data show that EPOR expression in t(12;21) B-ALL cells, is regulated by GATA2
      and is mediated through epigenetic, transcriptional and post-transcriptional
      mechanisms, contingent upon the genetic subtype of the disease.

PMID- 29029493
TI  - Systemic immune-inflammation index predicts the clinical outcome in patients with
      nasopharyngeal carcinoma: a propensity score-matched analysis.
AB  - Systemic immune-inflammation index (SII), based on peripheral lymphocyte,
      neutrophil, and platelet counts, was recently investigated as a prognostic marker
      in several tumors. However, SII has not been reported in nasopharyngeal carcinoma
      (NPC). We evaluated the prognostic value of the SII in 327 patients with NPC.
      Univariate and multivariate analyses were calculated by the Cox proportional
      hazards regression model. The time-dependent receiver operating characteristics
      (ROC) curve was used to compare the discrimination ability for OS. PSM
      (propensity score matching) was carried out to imbalance the baseline
      characteristics. Our results showed that SII, PLR, NLR and MLR were all
      associated with OS in NPC patients in the Kaplan-Meier survival analysis. SII
      (HR: 2.26; 95% CI: 1.40-3.66; P=0.001), NLR (HR: 1.66; 95% CI: 1.08-2.53;
      P=0.020), and MLR (HR: 1.99; 95% CI: 1.17-3.39; P=0.011) were identified to be
      the independent prognostic factors. The AUC for SII was bigger than NLR, PLR and
      MLR for predicting survival in patients with NPC in 3 or 5-years. In the PSM
      analysis, SII remained an independent predictor for OS in NPC patients (HR=2.08,
      CI 1.22-3.55, P=0.007). SII is a novel, simple and inexpensive prognostic
      predictor for patients with NPC. The prognostic value of SII is superior to PLR,
      NLR and MLR.

PMID- 29029494
TI  - KRAS overexpression independent of RAS mutations confers an adverse prognosis in
      cytogenetically normal acute myeloid leukemia.
AB  - The prognostic value of RAS mutations has been systematically investigated in
      acute myeloid leukemia (AML). However, clinical significance of RAS expressions
      in AML remains poorly determined. To explore the clinical significance, we
      analyzed KRAS and NRAS expressions in 143 de novo AML patients by real-time
      quantitative PCR. KRAS and NRAS expressions were significantly up-regulated in
      AML patients. KRAS and NRAS mutations were identified in 4% (6/143) and 8%
      (12/143) of these patients, respectively. However, no significant association was
      observed between RAS mutations and expressions. High KRAS expression was
      associated with older age, higher white blood cells, and a tendency of higher
      platelets, whereas high NRAS expression was only correlated with older age.
      Complete remission (CR) rate and overall survival of AML patients were adversely
      affected by KRAS overexpression, but not NRAS overexpression. Multivariate
      analysis revealed that KRAS acted as an independent prognostic predictor in
      cytogenetically normal AML (CN-AML). Moreover, the prognostic value of KRAS
      expression was validated using the published data from Gene Expression Omnibus
      datasets. In the follow-up patients, KRAS expression rather than NRAS expression
      in CR time tended to decrease compared to newly diagnosis time, and both KRAS and
      NRAS expressions were significantly increased when in relapse time. Our findings
      revealed that RAS overexpression and mutations were common events in AML with
      potential therapeutic target value. KRAS overexpression independent of RAS
      mutations conferred an adverse prognosis in CN-AML.

PMID- 29029496
TI  - 177Lu-PSMA-617 radioligand therapy for a patient with lymph node metastatic
      prostate cancer.
AB  - Prostate specific membrane antigen (PSMA) is expressed in unfavorable prostate
      cancer. PSMA is basis for new diagnostics and theranostics. PET/CT using PSMA is
      more sensitive than choline PET/CT. 177Lu-PSMA radioligand therapy is mainly used
      for patients with end-stage prostate cancer. This report describes a patient with
      a third recurrence in lymph nodes. The recurrence was treated with 177Lu-PSMA
      radioligand therapy instead of chemotherapy with docetaxel. The effect was in
      part evaluated relative to that of two established salvage treatments. Prior
      salvage radiotherapy and abiraterone of the first and second recurrence in lymph
      nodes had given only a partial reduction of PSA. Nevertheless within five months
      of follow-up, 177Lu-PSMA radioligand therapy of the third recurrence in lymph
      nodes reduced PSA for a period to unmeasurable levels. 177Lu-PSMA radioligand
      therapy gave only mild adverse effects. In conclusion, for a patient with lymph
      node metastatic prostate cancer, 177Lu-PSMA-617 radioligand therapy had an
      attractive therapeutic profile. A follow-up study of similar patients is being
      planned.

PMID- 29029495
TI  - Metadherin promotes metastasis by supporting putative cancer stem cell properties
      and epithelial plasticity in pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) has a high metastatic potential. However,
      the mechanism of metastatic colonization in PDAC remains poorly understood.
      Metadherin (MTDH) has emerged in recent years as a crucial mediator of metastasis
      in several cancer types, although the biological role of MTDH in PDAC has not
      been investigated. Here, we demonstrated the functional roles of MTDH in PDAC
      progression, especially focusing on the metastatic cascade. In vitro studies
      showed that MTDH provides cancer stem cell (CSC) properties in metastatic PDAC
      cells and contributes to anoikis resistance with epithelial characteristics in
      PDAC cells. We also performed in vivo studies using both orthotopic
      transplantation and intra-portal vein injection as experimental models of liver
      metastasis to examine the function of MTDH at the metastatic site. MTDH knockdown
      dramatically reduced the incidence of liver metastases along with epithelial
      features in both experimental mouse models. Collectively, MTDH facilitates
      metastatic colonization with putative CSC and epithelial properties in PDAC
      cells. PDAC cells were transiently treated with TGF-beta1 to investigate the
      roles of MTDH on epithelial plasticity. Intriguingly, MTDH expression was
      negatively correlated with Twist1 expression during the Mesenchymal-Epithelial
      transition (MET) induction in metastatic PDAC cells. These results suggest that
      MTDH may contribute to MET induction via downregulation of Twsit1. Lastly,
      immunohistochemistry indicated that MTDH overexpression is closely associated
      with hematogenous metastasis and predicts poor prognosis in patients with PDAC.
      This is the first demonstration of MTDH function in PDAC metastatic colonization.
      Our data suggest that MTDH targeting therapy could be applied to control PDAC
      metastasis.

PMID- 29029497
TI  - Kras mutation is a marker of worse oncologic outcomes after percutaneous
      radiofrequency ablation of colorectal liver metastases.
AB  - BACKGROUND: Kras mutation has been associated with shorter overall survival and
      time to disease recurrence after resection of colorectal liver metastases (CLM).
      This study evaluated the prognostic value of Kras mutation in patients with CLM
      treated by percutaneous radiofrequency ablation (RFA). METHODS: This is an IRB
      waived retrospective analysis of the impact of KRAS mutation status on oncologic
      outcomes after CLM RFA. The endpoints were overall survival (OS), local tumor
      progression (LTP) rates, and incidence of new liver, lung, and peritoneal
      metastases. Survival times were calculated using Kaplan-Meier methodology from
      the time of RFA. RESULTS: The study enrolled 97 patients. Kras exon 2 mutation
      was detected in 39% (38/97) of patients. On univariate analysis, Kras mutation
      (P=0.016) (HR: 1.8; 95% CI: 1.1 - 2.9) was a significant predictor of OS and
      retained significance on multivariate analysis. Kras mutation was a significant
      predictor of new liver metastases (P=0.037) (SHR: 2.0; CI: 1.0-3.7) and
      peritoneal metastases (P=0.015) (sHR: 3.0; 95% CI: 1.2-7.2) on multivariate
      analysis. Kras mutation was a significant predictor of LTP after RFA of CLM
      ablated with margins of 1-5 mm (P=0.018) (SHR: 3.0; 95% CI: 1.2-7.7) with an LTP
      rate of 80% (12/15) versus 41% (11/27) for wild type. CONCLUSION: Kras mutation
      is a significant predictor of overall survival, new liver, and peritoneal
      metastases after RFA of CLM. A minimal radiographic ablation margin >= 6 mm is
      essential for local tumor control especially for mutant CLM.

PMID- 29029498
TI  - Diffusion-kurtosis imaging predicts early radiotherapy response in nasopharyngeal
      carcinoma patients.
AB  - In this prospective study, we analyzed diffusion kurtosis imaging (DKI)
      parameters to predict the early response to radiotherapy in 23 nasopharyngeal
      carcinoma (NPC) patients. All patients underwent conventional magnetic resonance
      imaging (MRI) and DKI before and after radiotherapy. The patients were divided
      into response (RG; no residual tumors; 16/23 patients) and no-response (NRG;
      residual tumors; 7/23 patients) groups, based on MRI and biopsy results 3 months
      after radiotherapy. The maximum diameter of tumors in RG and NRG patients were
      similar prior to radiotherapy (p=0.103). The pretreatment diffusion coefficient
      (D) parameters (Daxis, Dmean and Drad) were higher in RG than NRG patients
      (p=0.022, p=0.027 and p=0.027). Conversely, the pre-treatment fractional
      anisotropy (FA) and kurtosis coefficient (K) parameters (Kaxis, Kfa, Kmean, Krad
      and Mkt) were lower in RG than NRG patients (p=0.015, p=0.022, p=0.008, p=0.004,
      p=0.001, p=0.002). The Krad coefficient (0.76) was the best parameter to predict
      the radiotherapy response. Based on receiver operating characteristic curve
      analysis Krad showed 71.4% sensitivity and 93.7% specificity (AUC: 0.897, 95% CI,
      0.756-1). Multivariate analysis indicated DKI parameters were independent
      prognostic factors for the short-term effect in NPC. Thus, DKI predicts the early
      response to radiotherapy in NPC patients.

PMID- 29029499
TI  - Generation and characterization of ErbB2-CAR-engineered cytokine-induced killer
      cells for the treatment of high-risk soft tissue sarcoma in children.
AB  - Pediatric patients with recurrent, refractory or advanced soft tissue sarcoma
      (STS) who are simultaneously showing signs of cumulative treatment toxicity are
      in need of novel therapies. In this preclinical analysis, we identified ErbB2 as
      a targetable antigen on STS cells and used cytokine-induced killer (CIK) cells
      transduced with the lentiviral 2nd-generation chimeric antigen receptor (CAR)
      vector pS-5.28.z-IEW to target ErbB2-positive tumors. Solely CIK cell subsets
      with the CD3+ T cell phenotype showed up to 85% cell surface expression of the
      respective CAR. A comparison of wildtype (WT), mock-vector and ErbB2-CAR-CIK
      cells showed, that engineered cells exhibited diminished in vitro expansion,
      retained WT CIK cell phenotype with higher percentages of differentiated effector
      memory/effector cells. Activating natural killer (NK) cell receptor NKG2D
      restricted target cell recognition and killing of WT and ErbB2-CAR-CIK cells was
      maintained against ErbB2-negative tumors, while ErbB2-CAR-CIK cells demonstrated
      significantly increased cytotoxicity against ErbB2-positive targets, including
      primary tumors. ErbB2-CAR- but not WT CIK cells proliferated, infiltrated and
      efficiently lysed tumor cell monolayers as well as 3D tumor spheroids. Here, we
      demonstrate a potential cell therapeutic approach using ErbB2-CAR-CIK cells for
      the recognition and elimination of tumor cells expressing ErbB2, which we
      identified as a targetable antigen on high-risk STS cells.

PMID- 29029500
TI  - EDG2 enhanced the progression of hepatocellular carcinoma by LPA/PI3K/AKT/ mTOR
      signaling.
AB  - HCC is the leading type of the malignant liver tumors with the unsatisfied
      prognosis. Liver resection has been considered as the predominant curative
      therapy, however, the post-surgical prognostic evaluation remains an urgent
      problem and the mechanism of HCC metastases has not been understood completely.
      EDG2 has been found to accelerate tumor progression through mediating different
      cell pathways, however, it remains unclear about the role of EDG2 on
      hepatocarcinogenesis. Here, EDG2 expression was found increased notably in HCC
      tissues by immunohistochemistry compared with adjacent liver tissues and
      comparison of survival curves revealed that EDG2 upregulation in HCC tissues was
      associated with the worse prognosis after liver resection. The positive
      correlation between EDG2 up-regulation and EMT was observed in HCC samples.
      Furthermore, EDG2 over-expression in HCC cells brought the typical EMT
      characteristics including up-regulation of Vimentin, Fibronectin and N-cadherin,
      suppression of E-cadherin, and enhanced cell migration and invasion capacities.
      Knockdown of EDG2 reversed the EMT phenotype in HCC cells. The in vivo
      experiments also identified the oncogenic role of EDG2 on HCC growth. The
      mechanistic studies elucidated that EDG2 enhanced mTOR phosphorylation via
      PI3K/AKT signaling and consequently induced EMT of HCC cells. Moreover, EDG2 was
      found to promote cell viability and proliferation of HCC cell through
      PI3K/AKT/mTOR/Skp2/p27Kip1 signaling. Taken together, the data here demonstrated
      EDG2 was a potential predictor for HCC patients receiving liver resection and
      accelerated HCC progression via regulating EMT driven by PI3K/AKT/mTOR signaling.

PMID- 29029501
TI  - Metformin and endometrial cancer survival: a quantitative synthesis of
      observational studies.
AB  - Metformin has been reported to have anticancer effect and can affect patient
      survival in several malignancies. However, the results are inconclusive for
      endometrial cancer. Hence, we conducted a systematic review and meta-analysis to
      investigate the prognostic role of metformin in patients with endometrial cancer.
      Studies were identified from Pubmed and Embase database through March 2017.
      Observational studies reporting hazard ratios (HRs) with 95% confidence intervals
      (CIs) for overall survival (OS) and progression-free survival (PFS) were
      selected. Data were abstracted and summarised using random-effects models. From
      250 unique citations, we identified ten studies including 6242 patients with nine
      studies examining OS and five studies examining PFS. Meta-analysis demonstrated
      that metformin users had better OS (HR, 0.58; 95% CI, 0.45 to 0.76; P = 0.207, I2
      = 26.6%) and PFS (HR, 0.61; 95% CI, 0.49 to 0.76; P =0.768, I2 = 0%) than non
      users for endometrial cancer patients. Similar findings were observed using
      sensitivity analysis adjusted by trim and filled methods (HR, 0.47; 95% CI, 0.37
      to 0.58) and subgroup analyses. Based on the current evidence, we find that
      metformin use is associated with better OS and PFS in patients with endometrial
      cancer. However, further large-scale prospective studies are needed to establish
      its validity.

PMID- 29029502
TI  - Clinicopathologic implications of the miR-197/PD-L1 axis in oral squamous cell
      carcinoma.
AB  - Immune escape of a tumor from tumor-infiltrating lymphocytes (TILs) is induced by
      PD-L1, which is suppressed by miR-197. We investigated the clinicopathologic
      implications of the miR-197/PD-L1 axis and its effects on TILs and the
      clinicopathologic features of oral squamous cell carcinoma (OSCC). We used RT-PCR
      and immunohistochemistry in 68 OSCC patients to analyze the correlations between
      tumoral expression of miR-197 and PD-L1 and the degree of tumoral invasion by
      TILs (CD3+, CD4+, CD8+, PD-1+, FoxP3+, and CD20+ lymphocytes). PD-L1 levels
      correlated inversely with miR-197 but correlated positively with TILs. The
      aggressive features of OSCC, including high stage, angiolymphatic invasion,
      perineural invasion, and death, were associated with TIL depletion. High T stage
      (T4) tumors also had low PD-L1 but had high miR-197 expression. In a univariate
      survival analysis of the full cohort, high miR-197 was associated with poor
      overall survival, whereas high PD-L1 expression (2+) associated with good overall
      survival. In a multivariate analysis stratified based on miR-197 (median), high
      PD-L1 expression (2+) was an independent favorable prognostic factor for overall
      survival (P = 0.040) in the miR-197high subgroup but not the miR-197low subgroup.
      These findings may have clinicopathologic implications for the miR-197/PD-L1 axis
      and TILs in OSCC.

PMID- 29029503
TI  - Slingshot-1L, a cofilin phosphatase, induces primary breast cancer metastasis.
AB  - Slingshot (SSH) is a member of the conserved family of cofilin phosphatases that
      plays a critical role in cell membrane protrusion and migration by transforming
      inactive phosphorylated cofilin to an active form. SSH-like protein 1 (SSH-1L)
      expression is detected in various types of tumors; insulin induces the
      phosphatases activity of SSH-1L in a phosphoinositide 3-kinase-dependent manner.
      However, little is known about the expression and role of SSH-1L in breast
      cancer. Here, we analyzed 295 human breast cancer tissue specimens for SSH-1L
      expression by immunohistochemistry. The correlation between SSH-1L level and
      patients' clinical characteristics was analyzed with Pearson's chi2 test. The
      function of SSH-1L was evaluated by gene knockdown and quantitative real-time
      polymerase chain reaction detection of cofilin expression in MDA-MB-231, MCF-7,
      and SK-BR-3 human breast cancer cell lines. SSH-1L expression was detected in
      88.1% of tissue specimens by immunohistochemistry and was strongly associated
      with increased metastasis and mortality. Loss of SSH-1L expression decreased the
      nonphosphorylated, active form of cofilin in SK-BR-3 and MDA-MB-231 cell lines,
      which was associated with reduced cell motility. Accordingly, SSH-1L/cofilin
      signaling played a critical role in primary breast cancer metastasis and was a
      potential therapeutic target for breast cancer treatment.

PMID- 29029504
TI  - Interleukin 10 gene rs1800896 polymorphism is associated with the risk of
      prostate cancer.
AB  - Numerous studies have uncovered the association of Interleukin-10 (IL-10) gene
      rs1800896 polymorphism with the risk of prostate cancer (PCa); however, their
      conclusions were inconsistent. Therefore, we conducted this meta-analysis to
      evaluate the role of IL-10 rs1800896 polymorphism in the risk of PCa. 16 eligible
      studies in 15 articles involving 6,301 cases and 6,510 controls were identified
      by researching PubMed, Google, CNKI, and EMBASE up to April 1, 2017. Our results
      revealed that IL-10 rs1800896 polymorphism was associated with the decreased risk
      of PCa under the homozygous model. Subgroup analysis by ethnicity revealed that
      rs1800896 polymorphism decreased the risk of PCa among Caucasians. In conclusion,
      IL-10 gene rs1800896 polymorphism is associated with the decreased risk of PCa.
      Larger studies with more diverse ethnic populations are needed to confirm these
      results.

PMID- 29029505
TI  - The deubiquitinating enzyme USP5 promotes pancreatic cancer via modulating cell
      cycle regulators.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid tumors.
      With an overall five-year survival rate remaining below 6%, there is an explicit
      need to search for new molecular targets for therapeutic interventions. We
      undertook a barcode labelled short-hairpin (shRNA) library screen in pancreatic
      cancer cells in order to identify novel genes promoting cancer survival and
      progression. Among the candidate genes identified in this screen was the
      deubiquitinase USP5, which subsequent gene expression analyses demonstrated to be
      significantly upregulated in primary human pancreatic cancer tissues. Using
      different knockdown approaches, we show that expression of USP5 is essential for
      the proliferation and survival of pancreatic cancer cells, tested under different
      2D and 3D cell culture conditions as well as in in vivo experiments. These growth
      inhibition effects upon knockdown of USP5 are mediated primarily by the
      attenuation of G1/S phase transition in the cells, which is accompanied by
      accumulation of DNA damage, upregulation of p27, and increased apoptosis rates.
      Since USP5 is overexpressed in cancer tissues, it can thus potentially serve as a
      new target for therapeutic interventions, especially given the fact that
      deubiquitinases are currently emerging as new class of attractive drug targets in
      cancer.

PMID- 29029506
TI  - Bitter melon extract inhibits breast cancer growth in preclinical model by
      inducing autophagic cell death.
AB  - Breast cancer is a major public health problem worldwide in women and current
      therapeutic strategies are not adequately effective for this deadly disease. We
      have previously shown the anti-proliferative activity of bitter melon extract
      (BME) in breast cancer cells. In this study, we observed that BME treatment
      induces autophagosome-bound Long chain 3 (LC3)-B and accumulates protein
      p62/SQSTM1 (p62) in breast cancer cells. Additionally, we observed that BME
      treatment in breast cancer cells increases phospho-AMPK expression and inhibits
      the mTOR/Akt signaling pathway. Subsequently, we demonstrated that BME feeding
      effectively inhibited breast cancer growth in syngeneic and xenograft mouse
      models. Further, we observed the increased p62 accumulation, induction of
      autophagy and apoptotic cell death in tumors from BME-fed animals. Taken
      together, our results demonstrate that BME treatment inhibits breast tumor
      growth, and this anti-tumor activity in breast cancer is, in part, mediated by
      induction of autophagy and modulation of the AMPK/mTOR pathway. The antitumor
      activity of BME by oral feeding in breast cancer models suggested the high
      potential for a clinical application.

PMID- 29029507
TI  - PIK3CA amplification and PTEN loss in diffused large B-cell lymphoma.
AB  - Although it has been known that PIK3CA was amplified and PTEN was deficient on
      protein level in DLBCL, the clinicopathological significance of PIK3CA and PTEN
      genetic change on DNA level hasn't been established. Here, in our present study,
      to understand the clinical significance of genetic status of PIK3CA and PTEN in
      DLBCL, fluorescent in-situ hybridization (FISH) was employed to evaluate the
      genetic change of PIK3CA and PTEN in clinical sample tissues consist of 205
      cases. Incidentally, to understand the clinicopathological significance of
      genetic change of PIK3CA and PTEN, Cross-table analysis was used to analyze the
      association between genetic change of PIK3CA and PTEN versus clinicopathological
      variables available to us, including age, gender, size, location, international
      prognosis index, performance state, B-symptom, clinical stage, Extra nodal site,
      concentration of lactate dehydrogenase, therapeutic effects, treatment and
      overall prognosis. It was found that PIK3CA was amplified and PTEN was deficient
      on DNA level, the percentage of amplification and loss was 12.7% (26/205) and
      12.2% (25/205), respectively. Additionally, no significant association was
      observed between genetic change of PIK3CA and PTEN versus clinicopathological
      variables available. Nor was the significant correlation found between loss of
      PTEN versus PIK3CA amplification. Our results suggest that PTEN deficiency and
      amplification of PIK3CA on DNA level was an event in the pathogenesis of DLBCL.

PMID- 29029508
TI  - Efficiency of low dosage apatinib in post-first-line treatment of advanced lung
      adenocarcinoma.
AB  - Chemotherapy is the standard treatment of in advanced lung adenocarcinoma
      patients without driver mutation. However, few drugs could be selected when
      diseases progressed after second-line treatment. As a small molecule inhibitor of
      vascular endothelial growth factor receptor-2 (VEGFR-2), apatinib was suggested
      mainly using in advanced gastric cancer. In this study, we showed the results of
      apatinib as second-line to fourth-line treatment in EGFR wild-type advanced lung
      adenocarcinoma patients. 16 EGFR wild-type advanced lung adenocarcinoma patients
      were administrated apatinib (250-500 mg/d) orally. 3 patients showed partial
      response and 8 patients showed stable diseases response to apatinib, with a
      medium progression-free survival (PFS) of 4.4 month (2-10 months). The objective
      remission rate (ORR) was 18.75%(3/16). The total disease control rate (DCR) was
      68.75% (11/16). The main toxicities were hypertension, hand-foot syndrome,
      proteinuria and thrombocytopenia which were tolerable and manageable. So,
      apatinib might be an optional choice for post-first-line treatment of EGFR wild
      type advanced lung adenocarcinoma patients.

PMID- 29029510
TI  - Adenovirus-mediated delivery of Sema3A alleviates rheumatoid arthritis in a serum
      transfer induced mouse model.
AB  - Rheumatoid arthritis is a chronic autoimmune disease characterized by
      infiltration of inflammatory cells into the synovium and destruction of cartilage
      and bone. Macrophages, fibroblast-like synoviocytes (FLS), and osteoclasts are
      critical cells driving the pathogenesis of RA. Semaphorin 3A (Sema3A) is recently
      identified as an essential player in the bone homeostasis, however its role in RA
      progression especially in the macrophage polarization are poorly understood. In
      the present study, we found that Sems3A levels were significantly decreased in RA
      serum and synovial fluid compared to OA controls. There was a negative
      correlation between Sema3A levels and RA severity. Using in vitro cell cultures,
      we showed for the first time that Sema3A promoted IL-4 induced M2 macrophage
      polarization, whereas prohibited LPS/IFN-gamma induced M1 polarization. Sema3A
      inhibited VEGF-induced endothelial cells proliferation and migration, suppressed
      VEGF-mediated invasion and IL-6 production of FLS while stimulating their
      apoptosis. In addition, Sema3A retarded osteoclastogenesis. In vivo data
      demonstrated that Sema3A administration attenuated joint tissue damage and the
      severity of experimental arthritis. Our findings uncovered Sema3A as a promising
      diagnostic biomarker and novel prevention and treatment strategies in arthritis
      treatment.

PMID- 29029509
TI  - Establishment of oral squamous cell carcinoma cell line and magnetic bead-based
      isolation and characterization of its CD90/CD44 subpopulations.
AB  - In this study, we describe the establishment of the human papillomavirus 18
      positive, stage II, grade 1, T2N0M0 head and neck tumor primary cell line derived
      from oral squamous cell carcinoma of a non-smoking patient by using two different
      protocols. Furthermore, a preparation of subpopulations derived from this primary
      cell line according to the cluster of differentiation molecules CD44/CD90 status
      using magnetic bead-based separation and their characterization was performed.
      Impedance-based real-time cell analysis, enzyme-linked immunsorbant assay
      (ELISA), wound-healing assay, flow-cytometry, gene expression analysis, and MTT
      assay were used to characterize these four subpopulations (CD44+/CD90-, CD44
      /CD90-, CD44+/CD90+, CD44-/CD90-). We optimised methodics for establishement of
      primary cell lines derived from oral squamous cell carcinoma tissue samples and
      subsequent separation of mesenchymal (CD90+) and epithelial (CD90-) types of
      tumorous cells. Primary cell line prepared by using trypsin proteolysis was more
      viable than the one prepared by using collagenase. According to our results, CD90
      separation is a necessary step in preparation of permanent tumor-tissue derived
      cell lines. Based on the wound-healing assay, CD44+ cells exhibited stronger
      migratory capacity than CD44- subpopulations. CD44+ subpopulations had also
      significantly higher expression of BIRC5 and SOX2, lower expression of FLT1 and
      IL6, and higher levels of basal autophagy compared to CD44- subpopulations.
      Furthermore, co-cultivation experiments revealed that CD44-/CD90+ cells supported
      growth of epithelial tumor cells (CD44+/CD90-). On the contrary, factors released
      by CD44+/CD90+ type of cells seem to have rather inhibiting effect. The most
      cisplatin-resistant subpopulation with the shortest doubling time was CD44
      /CD90+, but this subpopulation had a low migratory capacity.

PMID- 29029511
TI  - Mesenchymal stromal cells promote B-cell lymphoma in lacrimal glands by inducing
      immunosuppressive microenvironment.
AB  - Mesenchymal stromal cells (MSCs) have therapeutic potential for various diseases
      because of their anti-inflammatory and immunosuppressive properties. However, the
      immunosuppressive microenvironment allows tumor cells to evade immune
      surveillance, whereas maintenance of inflammation is required for tumor
      development and progression. Hence, MSCs may promote or suppress tumors in a
      context-dependent manner. We here investigated the effects of bone marrow-derived
      MSCs in a murine model of lacrimal gland B-cell lymphoma. Co-injection of MSCs
      with B lymphoma cells enhanced tumor growth in lacrimal glands without long-term
      engraftment. Of note, MSCs induced greater infiltration of immune and immune
      regulatory cells near tumor: CD4+ cells, CD11b+ cells, CD4+Foxp3+ regulatory T
      cells and CD11b+Ly6C+Ly6G- myeloid-derived suppressor cells. Concurrently, there
      was up-regulation of immune-related molecules including TNF-alpha, IL-1beta, TGF
      beta1, and arginase in glands treated with MSCs. Apoptosis in tumor was less
      severe in mice treated with MSCs compared to those without MSCs; however, MSCs
      did not directly inhibit apoptosis of B lymphoma cells in an in vitro co-culture.
      Together, data demonstrate that MSCs create immunosuppressive milieu by
      recruiting regulatory immune cells and promote B-cell lymphoma growth in lacrimal
      glands.

PMID- 29029512
TI  - PD-L1 expression indicates favorable prognosis for advanced lung adenocarcinoma
      patients treated with pemetrexed.
AB  - Conventional chemotherapy for lung cancer exerts anti-tumor effects through
      cytotoxicity, and through immunologic regulation by reducing specific T cell
      subsets and inducing the expression of programmed death ligand 1 (PD-L1) on tumor
      cells. Even though pemetrexed has shown huge potential in combination with other
      targeted or immune therapies, there is still little information about the values
      of specific immune checkpoint markers for advanced lung adenocarcinoma treated
      with pemetrexed. In the present study, a total of 56 patients with advanced lung
      adenocarcinoma, who received pemetrexed-based chemotherapy, were included
      retrospectively. Immunohistochemistry was performed to assess PD-L1, programmed
      death 1 (PD-1), thymidylate synthase, and tumor infiltrating lymphocytes (TILs).
      In this cohort, the positive expression of PD-L1 and PD-1 were 26.8% and 33.9%
      respectively. PD-L1, PD-1, and thymidylate synthase expression were not
      significantly associated with any clinical features, while the expression of both
      PD-L1 and PD-1 were correlated with Ki-67 expression. Furthermore, the expression
      of PD-1 was significantly correlated with TILs. The progression-free survival
      (PFS) in patients with PD-L1+ specimens was significantly longer compared to PD
      L1- specimens. Moreover, PD-L1 expression was an independent protective factor
      for PFS, and the smoking status was an independent risk factor. PD-L1 expression
      was significantly associated with better prognosis for patients with pemetrexed
      based treatment. Our findings suggested that PD-L1 expression might be a
      favorable prognostic biomarker for pemetrexed-based regimen, which is a rationale
      for combining immunotherapy with chemotherapy for lung cancer.

PMID- 29029513
TI  - Development of mesenchymal subtype gene signature for clinical application in
      gastric cancer.
AB  - Previously, in the Asian Cancer Research Group (ACRG) project, we defined four
      distinct molecular subtypes in gastric cancer (GC). Mesenchymal (microsatellite
      stable with epithelial-to-mesenchymal transition phenotype, MSS/EMT) tumors
      showed the worst prognosis among all the subtypes. To develop a gene signature
      for predicting mesenchymal subtype GC, we conducted gene expression profiling
      using a NanoString assay in 70 ACRG specimens. The gene signature was validated
      in an independent set obtained from the prospective Adjuvant chemoRadioTherapy In
      Stomach Tumor (ARTIST) trial. The association between the mesenchymal subtype and
      survival was investigated. After cross-platform concordance test performed in 70
      ACRG specimens, a 71-gene MSS/EMT signature was obtained. In the validation set,
      the gene signature predicted that 20 of 73 (27%) patients had mesenchymal tumors.
      Patients with mesenchymal subtype had diffuse GC, poorly-differentiated or signet
      ring cell carcinoma, and were microsatellite stable. The estimated hazard ratio
      for survival in patients with mesenchymal GC compared to those with non
      mesenchymal tumors was 2.262 (95% confidence interval, 1.410 to 3.636; P=0.001).
      The survival difference remained significant when the subtypes were analyzed
      according to clinical prognostic parameters. This study suggested that the
      NanoString-based 71-gene signature for mesenchymal subtype is a strong predictor
      of the outcome in patients with GC.

PMID- 29029514
TI  - Targeting of CCN2 suppresses tumor progression and improves chemo-sensitivity in
      urothelial bladder cancer.
AB  - Urothelial bladder cancer (UBC) is the most common urinary neoplasm in China. CCN
      family protein 2 (CCN2), a cysteine-rich matricellular protein, is abnormally
      expressed in several cancer types and involved in tumor progression or chemo
      resistance. However, detailed expression patterns and effects of CCN2 in UBC
      still remain unknown. We found that down-regulation of CCN2 suppressed
      proliferation, migration and invasion of UBC cells in vitro and targeting of CCN2
      decelerated xenograft growth in vivo. When treated with mitomycin C (MMC), CCN2
      scilencing UBC cells showed lower survival and higher apoptotic rates and these
      effects were probably mediated via inactivation of Akt and Erk pathways. We also
      demonstrated the clinical significance of CCN2 expression, which was higher in
      UBC tissues and associated with advanced tumor stage and high pathologic grade.
      Taken together, our data suggest that CCN2 is an oncogene in UBC and might serve
      as a matricellular target for improving chemotherapeutic efficacy.

PMID- 29029515
TI  - Discovery of NKCC1 as a potential therapeutic target to inhibit hepatocellular
      carcinoma cell growth and metastasis.
AB  - Metastasis is the essential cause for the high mortality of hepatocellular
      carcinoma (HCC). In order to investigate the mechanism of metastasis, and to
      discover therapeutic targets for HCC, the quantitative proteomic technique was
      applied to characterize the plasma membrane proteins of two HCC cell lines with
      low (MHCC97L) or high (MHCC97H) metastatic potentials. One of the plasma membrane
      proteins, sodium-potassium-chloride cotransporter 1 (NKCC1), was upregulated in
      MHCC97H cell line. Immunohistochemistry result in HCC patients showed that NKCC1
      expression was associated with poor differentiation and microvascular invasion.
      Knockdown of NKCC1 via RNA interference reduced HCC cell proliferation and
      invasion abilities in vitro and in vivo, whereas over-expression of NKCC1
      significantly increased HCC cell proliferation and invasion abilities in vitro
      and in vivo. Additionally, blocking NKCC1 activity with bumetanide attenuated the
      proliferation and invasion abilities of HCC cells in vitro and limited the HCC
      growth in vivo. Further results suggested that NKCC1 promotes the invasion
      ability via MMP-2 activity, and that the WNK1/OSR1/NKCC1 signal pathway might
      play roles in HCC metastasis. For the first time, our study demonstrated that
      NKCC1 plays a role in HCC metastasis, and could be served as a potential target
      to inhibit HCC cell growth and metastasis.

PMID- 29029516
TI  - The prognostic role of Sirt1 expression in solid malignancies: a meta-analysis.
AB  - Although many studies have discussed the association of abnormally expressed
      silent information regulator 1 (Sirt1) with the prognosis of patients with a
      variety of solid carcinomas, they failed to agree on whether excessive Sirt1
      indicates a good or poor overall survival for the patients. We conducted the
      current meta-analysis to illustrate the prognostic value of Sirt1 in solid
      malignancies. Articles published before December 2016 were searched using Pubmed
      and Web of Science. The studies were selected for the meta-analysis based on
      certain criteria. A total of 7,369 cases from 37 studies were included, in which
      48.6% of the patients overexpressed Sirt1. The overall survival (OS) and clinical
      features, such as age and TNM stage, were analyzed using RevMan 5.3 software.
      Sirt1 overexpression was significantly correlated with the OS (HR: 1.52, 95% CI:
      [1.23, 1.88], P = 0.0001), especially in liver cancer (HR: 1.78, 95% CI: [1.46,
      2.18], P < 0.00001) and lung cancer (HR: 1.80, 95% CI: [1.06, 3.05], P = 0.03),
      which suggested that the overexpression of Sirt1 indicates poor prognosis of
      patients with solid cancers.

PMID- 29029517
TI  - Prognostic value of HPV DNA status in cervical cancer before treatment: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Human papillomavirus (HPV), has been recognized as an vital
      preliminary event in the oncogenesis of cervical cancer. But the prognostic value
      is not well defined, because of past studies showing conflicting results. So we
      conducted this meta-analysis to evaluate whether HPV DNA status was associated
      with prognosis in cervical cancer. MATERIALS AND METHODS: A total of 17
      previously published eligible studies including 2,838 cases were identified and
      included in this meta-analysis. Positive HPV DNA was associated with good
      prognosis in patients with cervical cancer (overall survival [OS]: pooled hazard
      ratio (HR) = 0.610, 95% confidence interval (CI) = 0.457-0.814, P = 0.001;
      disease free survival [DFS]: pooled HR = 0.362, 95% CI = 0.252-0.519, P < 0.001).
      Furthermore, in subgroup analysis, the results revealed that the association
      between HPV DNA positive cervical cancers and better OS (pooled HR = 0.534, 95 %
      CI = 0.355-0.804, P = 0.003) in Mongoloid patients. Similarly, it existed in good
      OS (pooled HR = 0.628, 95 % CI 0.429-0.922, P = 0.017) and DFS (pooled HR =
      0.355, 95% CI = 0.226-0.559, P < 0.001) in Caucasian patients. CONCLUSIONS: HPV
      DNA status in cervical cancer may be a useful prognostic biomarker before
      carcinomas are treated. However, larger sample sizes and more comprehensive
      studies are required in the future studies to verify our findings.

PMID- 29029518
TI  - Meta-analysis of the clinical characteristics and prognostic relevance of NOTCH1
      and FBXW7 mutation in T-cell acute lymphoblastic leukemia.
AB  - The NOTCH1 signaling pathway is crucial for T-cell development, and NOTCH1 and/or
      FBXW7 mutations are frequently detected in T-cell acute lymphoblastic leukemia (T
      ALL). We performed a systematic review and meta-analysis of 18 randomized
      controlled trials (RCTs) to assess the prognostic impact of mutations in the
      NOTCH1 pathway. After retrieving relevant articles from PubMed, EMBASE, and the
      Cochrane Library, we investigated overall survival (OS) and event-free survival
      (EFS) with hazard ratios (HRs) using fixed-effects or random-effects models and
      conducted subgroup analyses based on population and mutation status. NOTCH1/FBXW7
      mutations correlated significantly with better prognosis (5-year EFS: HR, 0.57;
      95% confidence interval [CI], 0.46 to 0.68; P < 0.001 and 5-year OS: HR, 0.61;
      95% CI, 0.51 to 0.74; P < 0.001). The HR for 5-year EFS and OS with NOTCH1
      mutations were 0.63 (95% CI, 0.53 to 0.75) and 0.76 (95% CI, 0.60 to 0.95),
      respectively; with FBXW7 mutations, they were 0.82 (95% CI, 0.60 to 1.11) and
      0.79 (95% CI, 0.55 to 1.12), respectively. However, differences between children
      and adults showed no significance. We conclude that the presence of NOTCH1/FBXW7
      mutations is an independent prognostic factor for 5-year EFS and 5-year OS.

PMID- 29029519
TI  - Genetic polymorphisms in human UDP-glucuronosyltransferases 1A7 and the risk of
      gastrointestinal carcinomas: A systematic review and network meta-analysis.
AB  - OBJECTIVE: To identify the association between gastrointestinal carcinomas (GIC)
      risk and UDP-glucuronosyltransferases (UGTs) 1A7 polymorphisms through a
      systematic review and network meta-analysis. RESULTS: Seventeen studies were
      eligible, which included 7738 patients and 18 analyses. First, it was found that
      compared with non-cancer participants, UGT1A7*1 were significantly decreased in
      cancer patient groups, especially in hepatocellular carcinoma, colorectal
      carcinoma, and Asian population groups; UGT1A7*2 was significantly increased in
      hepatocellular carcinoma and Asian population groups; and UGT1A7*3 was
      significantly increased in hepatocellular carcinoma, colorectal carcinoma,
      Caucasian, and Asian population groups. Second, the UGT1A7 polymorphism alleles
      contrast model and the categorized UGT 1A7 genotypes were compared, and the
      outcomes revealed that the ratio of UGT1A7*3 vs *2 increased, which may indicate
      an increased risk for cancer, especially for the pancreatic carcinoma and
      Caucasian groups. The ratio of Intermediate vs Low increased as well, which may
      also indicate an increased risk for GIC. MATERIALS AND METHODS: PubMed, Embase,
      and the Cochrane library were searched for publications up until May 2017. First,
      the UGT 1A7 gene polymorphisms genotype in GIC patients were compared with a non
      cancer control group, and second, the UGT1A7 polymorphism alleles contrast model
      and UGT 1A7 genotypes categorized according to enzymatic activity were examined.
      CONCLUSIONS: There is a cancer risk associated with increased UGT1A7 *2 for the
      hepatocellular carcinoma and Asian groups and with increased UGT1A7 *3 for the
      hepatocellular carcinoma, colorectal carcinoma, Caucasian, and Asian groups.
      Moreover, in Caucasian patients with GIC, the ratio of UGT1A7 *3 vs *2 was
      increased.

PMID- 29029520
TI  - Prognostic role of intratumoral IL-17A expression by immunohistochemistry in
      solid tumors: a meta-analysis.
AB  - IL-17A is an important proinflammatory cytokine which is frequently elevated in
      tumor microenvironment. However, the role of intratumoral IL-17A in solid tumors
      remains controversial. Herein, we conducted a meta-analysis to assess the
      prognostic impact of intratumoral IL-17A in patients with solid tumor. PubMed and
      EBSCO were searched to identify the studies evaluating the associations between
      intratumoral IL-17A measured by immunohistochemistry (IHC) and overall survival
      (OS) and disease-free survival (DFS) in solid tumors. A total of 2972 patients
      with solid tumor from 21 published studies were incorporated into this meta
      analysis. We found that high level of intratumoral IL-17A was significantly
      associated with worse 3-year, 5-year OS and 1-year, 3-year DFS, but not with 1
      year OS or 5-year DFS in solid tumors. In addition, in stratified analyses by
      cancer types, IL-17A overexpression was significantly associated with worse OS in
      hepatic carcinoma, but with improved OS in esophageal squamous cell carcinoma
      (ESCC). Furthermore, high IL-17A expression positively correlated with advanced
      TNM stage. In conclusion, High expression of intratumoral IL-17A leads to an
      unfavorable clinical outcome in majority of solid tumors, implicating IL-17A is a
      valuable biomarker for prognostic prediction of human solid malignances and
      targeting it may have a potential for effective treatment.

PMID- 29029521
TI  - Contrast-enhanced endoscopic ultrasound for differential diagnosis of pancreatic
      cancer: an updated meta-analysis.
AB  - AIM: We aim to assess the diagnostic value of contrast-enhanced endoscopic
      ultrasound (CE-EUS) for pancreatic cancer and inflammatory lesions by pooling
      current evidence. MATERIALS AND METHODS: A systematical search of PubMed, Web of
      Science and the Cochrane Library was performed from inception to January 2016.
      Two authors independently screened and extracted detailed data from included
      studies. A random effect model was adopted to estimate the pooled sensitivity,
      specificity in order to determine the diagnostic ablitity of CE-EUS. Furthermore,
      we conducted the meta-regression and subgroup analyses to explore possible
      heterogeneity. RESULTS: Eighteen eligible studies enrolling 1668 patients were
      finally included in the study. The pooled sensitivity of CE-EUS for
      distinguishing pancreatic cancers from solid inflammatory masses was 0.93 (95%
      CI, 0.91-0.94), and the specificity was 0.88 (95% CI, 0.84-0.90). The area under
      summary receiver operating characteristic curve yielded 0.97. No publication bias
      was observed by Deeks' funnel plot in current meta-analysis. CONCLUSIONS: We
      provided evidence that CE-EUS is a promising modality for differential diagnosis
      of pancreatic adenocarcinomas. Further multicenter prospective studies should be
      carried out to certify its utility.

PMID- 29029522
TI  - Circulating miRNAs as novel diagnostic biomarkers in hepatocellular carcinoma
      detection: a meta-analysis based on 24 articles.
AB  - The diagnostic value and suitability of circulating miRNAs for the detection of
      hepatocellular carcinoma have been inconsistent in the literature. A meta
      analysis is used to systematically evaluate the diagnostic value of circulating
      miRNAs. Eligible studies were selected and the heterogeneity was assessed by
      subgroup analysis, meta-regression, and publication bias. After strictly and
      comprehensive screening, the source methods, internal reference and the cut-off
      values of the included miRNAs were first listed. Circulating miRNAs demonstrated
      a relatively good diagnostic value in hepatocellular carcinoma, In the subgroup
      analysis, diagnosis odds ratio showed a higher accuracy with multiple miRNAs than
      with a single miRNA as well as with serum types than plasma types. In addition,
      although miRNAs have many expression patterns, the high frequency expression
      miRNAs (miR-21, miR-199 and miR-122) might be more specific for the diagnosis of
      hepatocellular carcinoma.The sources of heterogeneity might be related to the
      number of miRNAs and the specimen types in meta-regression. Furthermore, it's
      surprised that the pooled studies were first demonstrated publication bias (P <
      0.05). In conclusion, multiple miRNAs in serum have a better diagnostic value,
      and the publication bias was stable. To validate the potential applicability of
      miRNAs in the diagnosis of hepatocellular carcinoma, more rigorous studies are
      needed to confirm these conclusions.

PMID- 29029523
TI  - Systematic review and meta-analysis of the utility of long non-coding RNA GAS5 as
      a diagnostic and prognostic cancer biomarker.
AB  - The growth arrest-specific 5 transcript (GAS5) is a long non-coding RNA (lncRNA)
      involved in the control of cell cycle progression and apoptosis in a wide variety
      of cells. To determine the clinical value of GAS5 expression in cancer patients,
      we performed a systematic review and meta-analysis exploring its association with
      the diagnosis, prognosis, and clinicopathological characteristics of cancer. Ten
      articles on prognosis, 15 on clinicopathology, and 5 on diagnosis were analyzed.
      Overall results showed that decreased GAS5 expression associated with unfavorable
      overall survival (OS) (HR = 2.50, 95%CI: 1.85-3.38, P < 0.001) and disease-free
      survival (DFS) (HR = 2.24, 95%CI: 1.58-3.18, P < 0.001) in several tumor types.
      Down-regulation of GAS5 correlated with poor recurrence-free survival (RFS) in
      hepatocellular carcinoma (HR = 2.40, 95%CI: 1.27-4.54, P = 0.007), and was
      associated with lymph node metastasis (OR = 1.92, 95% CI: 1.44-2.57, P < 0.001),
      distant metastasis (OR = 2.7, 95% CI: 1.05-6.97, P = 0.040), poor clinical stage
      (OR = 0.26, 95% CI: 0.18-0.38, P < 0.001), larger tumor size (OR = 3.21, 95% CI:
      2.08-4.95, P < 0.001), and poor tumor differentiation (OR = 1.98, 95% CI: 1.40
      2.80, P < 0.001). Pooled results of diagnostic data analysis showed that GAS5
      exhibited a sensitivity of 0.76 and specificity of 0.64 for cancer diagnosis, and
      an area under the curve of 0.76 (95% CI: 0.72-0.80) indicated moderate diagnostic
      accuracy. This meta-analysis suggests GAS5 lncRNA may be a useful diagnostic and
      prognostic cancer biomarker, and may be especially useful for identifying
      patients prone to developing lymph node or distant metastasis.

PMID- 29029524
TI  - Comparative efficacy and safety of antibody induction therapy for the treatment
      of kidney: a network meta-analysis.
AB  - To evaluate the efficacy and safety of antibody induction therapies in kidney
      transplantation. Systematic literature searches were undertaken using MEDLINE,
      Embase, and Cochrane Library database from 1980 to 2016. Randomized controlled
      trials (RCTs) comparing three antibody induction therapies (alemtuzumab,
      interleukin-2 receptor antibodies and antithymocyte globulin) between each other
      were identified. Bayesian network meta-analysis was used to combine both the
      direct and indirect evidence on treatment efficacy and its safety. Antibody
      induction therapy studies, comprising of 18 RCTs (3444 kidney transplant
      recipients), were included. Overall, alemtuzumab treatment was superior to the
      ATG group (OR: 0.49, 95% CI: 0.32 to 0.71) and IL-2RAs group (OR: 0.36, 95% CI:
      0.25 to 0.52) for reducing the 1-year acute rejection in kidney transplant
      recipients. Although alemtuzumab treatment was nearly same with ATG group and IL
      2RAs group in improving patient survival and renal function, it can reduce the
      adverse effects of cytomegalovirus infection more efficiently than ATG group (OR:
      0.59, 95% CI: 0.32 to 0.95) and IL-2RAs group (OR: 1.08, 95% CI: 0.61 to 1.73).
      Alemtuzumab was not associated with increased other adverse effects. Alemtuzumab
      treatment is safe and effective for kidney transplant recipients. No serious
      adverse effects were observed in trials or in general populations.

PMID- 29029525
TI  - Association between air pollution and cardiovascular mortality in China: a
      systematic review and meta-analysis.
AB  - Air pollutant levels in many Chinese cities remained significantly higher than
      the upper limits stated in World Health Organization guidelines. In light of
      limited evidence in China, we conducted a meta-analysis summarizing the
      association between acute exposure of air pollution and cardiovascular mortality.
      We searched PubMed, and CNKI databases etc. for literature published in English
      or Chinese up to January 2017. Outcomes were pooled and compared using random
      effects model. Excess risks (ERs) per 10 MUg/m3 increase in PM2.5, PM10, NO2, SO2
      and O3 were evaluated. Subgroup analysis was conducted according to lag patterns
      (lags 0, 1, 2, 0-1, 0-2 days), gender (male vs. female), temperature (cool vs.
      warm) and age (< 65 vs. >= 65). Study bias was detected using Begg's and Egger's
      test. Of 299 articles identified, 30 met inclusion criteria. Each 10 MUg/m3
      increase in the concentration was associated with a higher incidence of
      cardiovascular mortality for PM2.5 (0.68%, 95% CI: 0.39-0.97%), PM10 (0.39%, 95%
      CI: 0.26-0.53%), NO2 (1.12%, 95% CI: 0.76-1.48%), SO2 (0.75%, 95% CI: 0.42
      1.09%), and O3 (0.62%, 95% CI: 0.33-0.92%), respectively. Air pollution conferred
      greater adverse impacts on cardiovascular mortality for longer duration of
      exposures. Strongest associations were seen for lag 0-1 day of exposure among all
      pollutants. Female, lower temperature, and age > 65 years were associated with
      greater risks of cardiovascular mortality for all pollutants. Higher
      concentrations of air pollutants correlated with a greater short-term increase in
      cardiovascular mortality. Further high-quality studies in China are urgently
      warranted to determine the susceptible population, which would offer reference
      for policy-making to minimize adverse health effects.

PMID- 29029526
TI  - Percutaneous coronary intervention using drug-eluting stents versus coronary
      artery bypass graft surgery in left main coronary artery disease an updated meta
      analysis of randomized clinical trials.
AB  - OBJECTIVES: To compare the safety and efficacy of percutaneous coronary
      intervention (PCI) using drug-eluting stent (DES) and coronary artery bypass
      graft (CABG) for the treatment of left main coronary artery (LMCA) disease.
      BACKGROUND: Several new randomized trials have recently examined the clinical
      outcomes of PCI and CABG in LMCA disease. However, the results of these studies
      were inconsistent. MATERIALS AND METHODS: We searched five online electronic
      databases to identify all the randomized clinical trials assessing the outcomes
      of PCI using DES and CABG in patients with LMCA. The clinical outcomes were the
      major adverse cardiac and cerebrovascular event (MACCE), all-cause death,
      myocardial infarction (MI), stroke, and repeat revascularization (RR). RESULTS: A
      total of 5 randomized clinical trials with 4595 LMCA patients were included in
      this meta-analysis. For one year follow-up, the results indicated that PCI were
      associated with a lower risk of stroke (RR = 0.21, 95% CI = 0.07-0.65, P =
      0.007), a higher risk of RR (RR = 1.72, 95% CI = 1.28-2.33, P < 0.001) than CABG.
      Moreover, for long-term follow-up, there were significant higher risks of MACCE
      and RR with PCI versus CABG (MACCE: HR = 1.26, 95% CI = 1.11-1.44, P = 0.001; RR:
      HR = 1.70, 95% CI = 1.42-2.05, P < 0.001). However, there were no significant
      differences between the two groups in all-cause death and MI risks, regardless of
      follow-up duration. CONCLUSIONS: PCI is noninferior to CABG in short term follow
      up of patients with LMCA disease, but CABG is more safety and efficacy than PCI
      using DES in long-term follow-up.

PMID- 29029527
TI  - Targeted first-line therapies for advanced colorectal cancer: a Bayesian meta
      analysis.
AB  - BACKGROUND: Colorectal cancer is common and deadly. First-line treatments for
      patients with metastatic disease include FOLFIRI and FOLFOX, which have been
      combined with anti-EGFR or anti-VEGF antibodies to achieve benefit in selected
      populations. However, optimal therapy remains unclear. RESULTS: Fifteen
      publications on 10 trials were identified. There was a lack of decisive evidence
      that FOLFIRI or FOLFOX impact efficacy of either anti-EGFR or anti-VEGF, across
      mutational status groups. On the other hand, evidence suggests both anti-EGFR and
      anti-VEGF may be more effective for KRAS WT than MT patients. KRAS WT results
      provided evidence that anti-EGFR treatments may be more effective than anti-VEGF
      treatments when combined with FOLFIRI or FOLFOX. Further, evidence suggests that
      both anti-EGFR and anti-VEGF therapies, when combined with FOLFIRI or FOLFOX, may
      be harmful as compared to chemotherapy for KRAS MT patients. MATERIALS AND
      METHODS: Literature was searched for randomized trials comparing anti-EGFR or
      anti-VEGF antibodies, paired with FOLFIRI or FOLFOX, as first-line therapy for
      advanced colorectal cancer. Meta-estimates were generated via Bayesian
      hierarchical log-linear model. The primary endpoint was overall survival.
      CONCLUSIONS: Further studies examining impact of all-RAS mutation status, left or
      right side location of primary tumor, and combination anti-VEGF with modern bolus
      fluoropyrimidine are needed.

PMID- 29029528
TI  - Loss of heterozygosity on chromosome 16q increases relapse risk in Wilms' tumor:
      a meta-analysis.
AB  - Wilms' tumor (WT) is the most frequent malignant renal tumor in children. The
      survival rate is lower in patients with recurrence, and the factors that
      influence relapse in WT are not fully understood. Loss of heterozygosity on
      chromosome 16q (LOH 16q) has been reported to be associated with the relapse in
      WT, but this remains controversial. We performed a meta-analysis to clarify this.
      PUBMED, EMBASE, and the Cochrane Library were searched up to March 17, 2017. Ten
      studies involving 3385 patients were ultimately included in the meta-analysis.
      The meta-analysis showed that LOH 16q was significantly associated with the
      relapse in WT (relative risk [RR] = 1.74, 95% confidence interval [CI] = 1.43
      2.13, P < 0.00001; hazard ratio [HR] = 1.76, 95% CI = 1.38-2.24, P < 0.00001). No
      significant heterogeneity among studies or publication bias was found.
      Sensitivity analysis showed omitting one study in each turn could not change the
      results. Subgroup analysis based on two studies indicated LOH 16q was more
      effective on elevated replase risk in patients with favorable-histology WT (RR =
      2.52, 95% CI = 1.68-3.78, P < 0.00001; HR = 2.99, 95% CI = 1.84-4.88, P < 0.0001)
      but further work are needed to confirm this. These findings confirm that LOH 16q
      increased the relapse risk in WT, but more studies are required to further assess
      the association between LOH 16q and WT relapse among different subgroups.

PMID- 29029529
TI  - The roles of maspin expression in gastric cancer: a meta- and bioinformatics
      analysis.
AB  - Maspin is a mammary serine protease inhibitor that is encoded by human SERPINB5
      gene, and inhibits invasion and metastasis of cancer cells as a tumor suppressor.
      We performed a systematic meta- and bioinformatics analysis through multiple
      online databases up to Feb 10, 2017. We found down-regulated maspin expression in
      gastric cancer, compared with normal mucosa and dysplasia (p < 0.05). Maspin
      expression was negatively correlated with depth of invasion, TNM staging and
      dedifferentiation of gastric cancer (p < 0.05). Nuclear maspin expression was
      higher in intestinal- than diffuse-type carcinoma (p < 0.05). An inverse
      association between maspin expression and unfavorable overall survival was found
      in patients with gastric cancer (p < 0.005). According to bioinformatics
      databases, SERPINB5 mRNA expression was higher in gastric cancer than normal
      tissues (p < 0.05), and negatively correlated with depth of invasion, TNM staging
      and dedifferentiation of gastric cancer (p < 0.05). According to KM plotter, we
      found that a higher SERPINB5 expression was positively correlated with overall
      and progression-free survival rates of all cancer patients, even stratified by
      aggressive parameters (p < 0.05). These findings indicated that maspin expression
      might be employed as a potential marker to indicate gastric carcinogenesis,
      subsequent progression, and even prognosis.

PMID- 29029530
TI  - Which treatment is preferred for advanced non-small-cell lung cancer with wild
      type epidermal growth factor receptor in second-line therapy? A meta-analysis
      comparing immune checkpoint inhibitor, tyrosine kinase inhibitor and
      chemotherapy.
AB  - BACKGROUND: The recommendations regarding the optimum treatment for advanced non
      small-cell lung cancer (NSCLC) patients with wild-type (WT) epidermal growth
      factor receptor (EGFR) tumors remain unclear. This meta-analysis was conducted to
      assess the efficacy among programmed death-ligand 1 (PD-L1)/programmed death-1
      (PD-1) antibody, EGFR-tyrosine kinase inhibitors (TKI) and chemotherapy in second
      and third-line therapy. PATIENTS AND METHODS: Randomized trials investigating two
      of the three treatments were searched and included. Multiple treatments
      comparison and pairwise comparison were performed to assess overall survival (OS)
      and progression-free survival (PFS), expressed as hazard ratios (HRs). The effect
      of prespecified study-level characteristics was assessed by subgroup analysis and
      meta-regression. RESULTS: 12 randomized trials accruing 3341 advanced patients
      with WT EGFR tumors were analyzed. PD-1/PD-L1 antibody was associated with
      significantly longer OS and PFS than chemotherapy (OS: HR 0.67, 95% CrI 0.60
      0.75; PFS: HR 0.83, 95% CrI 0.73-0.95) and TKI (OS: HR 0.59, 95% CrI 0.50-0.70;
      PFS: HR 0.75, 95% CrI 0.66-0.84) , while chemotherapy was associated with
      significantly longer OS (HR 0.88, 95% CrI 0.77-0.99) and PFS (HR 0.75, 95% CrI
      0.66-0.84) than TKI. CONCLUSIONS: For advanced NSCLC patients with WT-EGFR tumors
      in second- or third-line therapy, PD-1/PD-L1 antibody appeared to be the most
      efficacious treatment, which was followed by chemotherapy. EGFR-TKI was worse
      than chemotherapy.

PMID- 29029531
TI  - Efficacy and safety of pramlintide injection adjunct to insulin therapy in
      patients with type 1 diabetes mellitus: a systematic review and meta-analysis.
AB  - AIMS: We aim to assess the efficacy and safety of pramlintide plus insulin
      therapy in patients with type 1 diabetes. METHODS: We included clinical studies
      comparing pramlintide plus insulin to placebo plus insulin. Efficacy was
      reflected by glycemic control and reduction in body weight and insulin use.
      Safety concerns were hypoglycemia and other adverse events. Subgroup analysis was
      performed for different doses (30, 60, 90 ug/meal) and durations (<=4, 26, 29,
      >29 weeks) of the treatment. RESULTS: A total of 10 randomized placebo-controlled
      studies were included for this meta-analysis (pramlintide, n=1978; placebo,
      n=1319). Compared with controls, patients given pramlintide had significantly
      lower HbA1c (p < 0.001), total daily insulin dose (p = 0.024), mean mealtime
      insulin dose (p < 0.001), body weight (p < 0.001) and postprandial glucose level
      (p = 0.002). The addition of pramlintide increased the incidence of nausea (p <
      0.001), vomiting (p < 0.001), anorexia (p < 0.001) and hypoglycemia (p < 0.05) at
      the initiation of the treatment. The efficacy and adverse reactions of
      pramlintide were largely significant for the different doses and durations of the
      treatment. CONCLUSIONS: The addition of pramlintide to insulin therapy in
      patients with type 1 diabetes improves glycemic control and reduces insulin
      requirement and body weight while bringing transient hypoglycemia and digestive
      disorders.

PMID- 29029532
TI  - 11C-choline PET/CT and whole-body MRI including diffusion-weighted imaging for
      patients with recurrent prostate cancer.
AB  - PURPOSE: To compare the detection efficacy of 11C-choline positron emission
      tomography and computed tomography (PET/CT) with whole-body magnetic resonance
      imaging (MRI) including diffusion-weighted imaging (DWI) in patients with
      suspected recurrent prostate cancer. MATERIALS AND METHODS: Fifty-seven patients
      (mean age 68, range 54-80 years) underwent 11C-choline PET/CT and MRI using T1
      weighted (T1w), short-tau inversion recovery (STIR), and DWI. Two readers
      visually rated suspicious lesions on a 5-point scale in 20 different regions.
      Clinical follow-up and histopathology served as the standard of reference (SOR).
      RESULTS: Fifty patients (mean PSA 29.9, range 1.0-670 ng/mL) had at least one
      positive lesion according to the SOR. Twenty-four patients had local recurrence
      (LR), 27 had lymph node (LN) involvement, and 22 had bone metastases. The overall
      detection rates for PET/CT and MRI on a patient basis were 94% and 88%,
      respectively (p = 0.07). The PSA level (>2 ng/mL vs <=2 ng/mL) significantly
      influenced the overall performance of PET/CT (p = 0.003) and MRI (p = 0.03).
      PET/CT was significantly superior to MRI in detecting LR (p = 0.03) and bone
      metastasis (p = 0.02). We found no difference with respect to the detection of LN
      metastasis (p = 0.65). CONCLUSION: 11C-choline PET/CT was superior in the
      detection of local recurrence and bone metastasis on a regional basis. Whole-body
      MRI including DWI showed similar diagnostic accuracy only for detecting lymph
      node metastases. Compared with 11C-choline PET/CT, therefore, whole-body MRI
      including DWI cannot serve as alternative imaging modality for restaging prostate
      cancer.

PMID- 29029533
TI  - The immune impact of mimic endoscopic retrograde appendicitis therapy and
      appendectomy on rabbits of acute appendicitis.
AB  - This study was conducted to evaluate the immune impact of mimic endoscopic
      retrograde appendicitis therapy and appendectomy on rabbits of acute suppurative
      appendicitis and to determine whether TLR4/MYD88/NF-kappaB signaling pathway was
      activated in this process. 48 rabbits were assigned into 4 groups: group I, the
      mimic endoscopic retrograde appendicitis therapy group; group II, the
      appendectomy group; group III, the model group; and group IV, the blank group.
      White blood cells decreased, while levels of C-reactive protein, tumor necrosis
      factor-alpha, interleukin-6, interleukin-4, and interleukin-10 increased on the
      2nd day in group I and II. IgA in feces decreased at 2 weeks, while fecal
      microbiota changed at 2 and 4 weeks after appendectomy. CD8+ cells in appendix of
      group I increased within 8 weeks. Upregulated expression of TLR4, MYD88, and
      nuclear NF-kappaB were detected on the 2nd day in group I and II. Mimic
      endoscopic retrograde appendicitis therapy and appendectomy are effective ways
      for acute suppurative appendicitis. Mimic endoscopic retrograde appendicitis
      therapy was more preferable due to its advantage in maintaining intestinal immune
      function. TLR4/MYD88/NF-kappaB signaling pathway was activated in acute phase of
      appendicitis.

PMID- 29029535
TI  - Leucine-rich alpha-2-glycoprotein-1, relevant with microvessel density, is an
      independent survival prognostic factor for stage III colorectal cancer patients:
      a retrospective analysis.
AB  - BACKGROUND: Leucine-rich alpha-2-glycoprotein-1 (encoded by LRG1) has been shown
      to be involved in multiple cancer progression and angiogenesis. LRG1 has been
      shown to be one of the five plasma proteins that can be used for colorectal
      cancer (CRC) diagnosis. The objective of the current study was to explore
      relationship between LRG1 protein expression and microvessel density (MVD) in
      stage III CRC. METHODS: A single-center retrospective analysis of all stage III
      CRC who underwent surgery and adjuvant chemotherapy was carried out. LRG1 and
      CD34 were tested in tumor tissues by immunohistochemistry (IHC). RESULTS: LRG1
      protein expression was significantly associated with MVD (P <0.001) and other
      clinicopathological parameters, including T stage (P=0.028), differentiation
      (P=0.035) and vascular invasion (P=0.007). Cox multivariate regression analysis
      showed that LRG1 protein expression was an independent poor predictive factor for
      both disease-free and overall survival. CONCLUSION: LRG1 protein expression can
      be used as a prognostic marker for stage III CRC along with its use as a
      diagnostic marker for CRC in general.

PMID- 29029534
TI  - Is preoperative chronic kidney disease status associated with oncologic outcomes
      in upper urinary tract urothelial carcinoma? A multicenter propensity score
      matched analysis.
AB  - PURPOSE: The aim of this study was to determine the effect of preoperative
      chronic kidney disease (CKD) on the prognosis of patients with upper urinary
      tract urothelial carcinoma (UTUC) who had undergone radical nephroureterectomy
      (RNU). RESULTS: The median follow-up period was 31.1 months (interquartile range:
      16.2-55.7 months). Among the study patients, 224 patients in the non-CKD group
      were selected via propensity score matching. The median recurrence-free, cancer
      specific, and overall survival were significantly shorter for patients with
      preoperative CKD than for non-CKD patients (p = 0.001, p = 0.001, and p = 0.001,
      respectively). According to multivariable Cox regression analysis, preoperative
      CKD was related to worse recurrence-free (hazard ratio [HR]: 1.81, 95% confidence
      interval [CI]: 1.15-2.86, p = 0.011), cancer-specific (HR: 2.44, 95% CI: 1.44
      4.14, p = 0.001), and overall survival (HR: 1.66, 95% CI: 1.15-2.40, p = 0.007).
      METHODS: A total of 566 patients who underwent RNU at 6 institutions from 2004 to
      2014 were retrospectively reviewed. Of these patients, 342 had an estimated
      glomerular filtration rate (eGFR) >= 60 ml/min/1.73 m2 (non-CKD group) and 224
      patients had an eGFR <60 ml/min/1.73 m2 (CKD group). To adjust for potential
      baseline confounders, 224 patients in the non-CKD group were selected by
      propensity matching. Clinicopathological variables and survival rates were
      compared between the 2 groups. CONCLUSIONS: Preoperative CKD appears to be an
      important independent prognostic factor for oncologic outcomes in patients with
      UTUC.

PMID- 29029536
TI  - The optimal chemotherapeutic regimen in D2-resected locally advanced gastric
      cancer: a propensity score-matched analysis.
AB  - Adjuvant chemotherapy using TS-1 or capecitabine plus oxaliplatin improves
      survival outcomes after radical gastrectomy, with both regimens showing similar
      efficacies. A total of 494 patients with stage II-III gastric cancer who
      underwent curative D2 gastrectomy and received adjuvant chemotherapy from April
      2004 to June 2014 were included in this study. 219 patients received TS-1, and
      275 received platinum-based chemotherapy. The disease-free survival associated
      with adjuvant chemotherapy with TS-1 was compared with that associated with
      fluoropyrimidine plus platinum chemotherapy to identify the subgroups that would
      benefit most from platinum-based chemotherapy. The platinum group consisted of
      younger individuals, more males and more stage III patients compared with the TS
      1 group. To reduce selection bias and its effects on treatment results, we
      performed a propensity score-matched analysis. The matched cohort consisted of
      219 TS-1 and 219 platinum treatment patients, respectively. In the matched
      cohort, the chemotherapeutic regimen did not affect disease-free survival
      according to stage (stage II: platinum vs. TS-1, P = 0.348; stage III: P =
      0.132). According to the subgroup analysis, platinum-based chemotherapy resulted
      in an improved 3-year disease-free survival compared with TS-1 treatment (66.8%
      vs. 57.8%, P = 0.015) for patients with high-risk features (any two or more of
      pT4, pN3, and lymphovascular invasion positivity). Our results suggest that TS-1
      alone is acceptable for patients without high-risk features, while platinum-based
      adjuvant chemotherapy should be administered to patients with high-risk features
      in D2-resected gastric cancer.

PMID- 29029537
TI  - The synergistic effect of dual use of amphetamine-type stimulants and ketamine on
      drug-induced psychotic symptoms in Chinese synthetic drug users.
AB  - The use of amphetamine-type stimulants (ATS) and ketamine is of particular
      clinical concern because of its associated psychotic symptoms. In Chinese
      clinical practice, ATS and ketamine are commonly used simultaneously, but very
      few studies have reported the symptom profile of users who use both drugs. This
      study determined whether the combined use of ATS and ketamine is associated with
      more psychotic symptoms than either ATS or ketamine alone. According to drug use
      characteristics, 375 Chinese synthetic drug users were categorized into 2 pairs
      of comparison groups: ATS-only (n=125) vs. ATS-mainly (ATS most of the time and
      ketamine sometimes, n=150) and ketamine-only (n=38) vs. ketamine-mainly (ketamine
      most of the time and ATS sometimes, n=62). We used the Chinese Brief Psychiatric
      Rating Scale (BPRS) to assess these patients' psychotic symptoms. ATS-mainly
      group had more anxiety/depression and anergia symptoms than ATS-only group
      (p<0.001), and ketamine-mainly group had more thinking-disorder, activity and
      hostility-suspicion symptoms than ketamine-only group (p<=0.001). These findings
      indicate that ATS may exacerbate the thinking-disorders, activity and hostility
      suspicion symptoms of ketamine users, and ketamine may exacerbate
      anxiety/depression and anergia symptoms of ATS users.

PMID- 29029538
TI  - Visceral pleural invasion predict a poor survival among lung adenocarcinoma
      patients with tumor size <= 3cm.
AB  - INTRODUCTION: The impact of visceral pleural invasion (VPI) on survival remains
      controversial for patients with early stage non-small cell lung cancer (NSCLC).
      This study investigated the survival status of VPI among patients with lymph node
      negative lung invasive adenocarcinoma smaller than 3cm. METHODS: We
      retrospectively reviewed 2537 consecutive patients with pathologic stage I lung
      invasive adenocarcinoma. All patients had received lobectomy and system lymph
      nodes resection. Patients were classified into 4 groups according to tumor size
      and visceral pleural invasion status. Disease-free survival (DFS) and overall
      survival (OS) were analyzed to evaluate survival difference between these groups.
      RESULTS: 548 patients with VPI while 1989 patients without VPI were included in
      this study. For patients with tumor size <=2cm, patients with VPI had significant
      worse DFS (HR,4.85; 95% CI, 2.98-7.91; p = .000) and OS(HR,3.52; 95% CI, 1.59
      7.78; p = .002) compared with non-VPI group. For patients with tumor size between
      2-3cm, patients with VPI had significant worse DFS (HR, 1.72; 95% CI, 1.16-2.55;
      p = .006) but no significant OS (HR, 1.31; 95% CI, 0.76-2.24; p = .330) compared
      with non-VPI group. For patients with VPI, there were no survival difference
      between tumor size 2-3cm group and <=2cm group for both DFS(HR,1.02; 95% CI, 0.65
      1.61; p = .939) and OS(HR,1.45; 95% CI, 0.71-2.97; p = .315). CONCLUSIONS: VPI
      could predict a poor survival even for node-negative invasive lung adenocarcinoma
      patients with tumor size less than 3cm.

PMID- 29029539
TI  - Therapeutic evaluation of arterio-portal fistula-related gastroesophageal
      variceal bleeding.
AB  - BACKGROUND & AIMS: Intrahepatic arterio-portal fistula is an uncommon etiology of
      portal hypertension, which presents diagnostic and therapeutic challenges. This
      study aimed to assess the efficacy and outcomes of gastroesophageal variceal
      bleeding caused by arterio-portal fistula using different therapeutic approaches.
      METHODS: Medical records of 451 consecutive patients with arterio-portal fistula
      were reviewed from January 1, 2009, to July 15, 2016, and patients suffered
      variceal bleeding were eligible for the study. RESULTS: Among 57 patients with
      arterio-portal fistula, hepatocellular carcinoma was existed in 61.4% patients. A
      combination of radiological intervention and endoscopic treatment was performed
      in 8 (14.0%) patients; the remainder were treated using radiological intervention
      alone (n = 20, 35.1%), endoscopic treatment alone (n = 18, 31.6%), or without any
      intervention (n = 11, 19.3%). No patient died in the combination group, while 20
      patients in the single-treatment group and 6 in the untreated group died during
      follow-up. A significant difference in the survival rate was found between the
      combination group and the other two groups. Treatment selection between
      combination and untreated groups was the only parameter significantly associated
      with survival (p = 0.002). CONCLUSIONS: For patients diagnosed with arterio
      portal fistula, combination treatment is the most optimal strategy in managing
      variceal bleeding, especially in patient with severe type of fistula.

PMID- 29029540
TI  - Timing of chemotherapy-induced neutropenia: the prognostic factor in advanced
      pancreatic cancer patients treated with gemcitabine / gemcitabine-based
      chemotherapy.
AB  - Chemotherapy-induced neutropenia (CIN) was reported to be a predictor of better
      survival in several cancers. The objective of our study is to evaluate the
      relationship between the timing (onset) of CIN and prognosis. Between June 2008
      and June 2015, 134 patients with confirmed advanced pancreatic cancer received at
      least one cycle of gemcitabine / gemcitabine-based chemotherapy as first-line
      chemotherapy were eligible for assessment. Timing of CIN was categorized into
      early onset and non-early onset CIN group. The end of cycle 2 was the cutoff to
      differentiate early onset or non-early onset. The correlation between timing of
      CIN with survival was analyzed by Kaplan-Meier method and Cox proportional
      hazards model. Median overall survival (OS) was 8.05 months (95% CI: 5.97-10.13)
      for patients with early onset CIN compared with 5.82 months (95% CI: 5.00-6.63)
      for patients without early-onset neutropenia (P = 0.022). Multivariate analysis
      proved that timing of CIN was an independent prognostic factor, hazard ratios of
      death was 0.696 (95% CI: 0.466-0.938) for patients with early onset CIN. In
      conclusion, timing of CIN is an independent predictor of prognosis in patients
      with advanced pancreatic cancer undergoing gemcitabine / gemcitabine based
      chemotherapy. Early-onset CIN predicts better survival.

PMID- 29029542
TI  - Comprehensive analysis on diagnostic value of circulating miRNAs for patients
      with ovarian cancer.
AB  - We performed a meta-analysis to assess the diagnostic accuracy of circulating
      miRNA for patients with ovarian cancer. We systematically searched several online
      databases, including PubMed, Web of Science, Chinese National Knowledge
      Infrastructure, and Wanfang from inception to February 20, 2017. We used the
      bivariate mixed-effect models to pool positive likelihood ratios, negative
      likelihood ratios, diagnostic odds ratios and their 95% CI confidence intervals
      (CIs). We used the Quality Assessment of Diagnostic Accuracy Studies 2 for
      quality assessment of diagnostic accuracy studies. This meta-analysis included
      ten studies with the number of 1356 participants. The pooled sensitivity and
      specificity were 0.75 (95%CI: 0.69-0.80) and 0.75 (95%CI: 0.69-0.81). We also
      calculated the positive likelihood ratios (3.03, 95%CI: 2.44-3.76), and negative
      likelihood ratios (0.33, 95%CI: 0.27-0.41). The diagnostic odds ratio was 9.09
      (95%CI: 6.51-12.69). The summary receiver operator characteristic was 0.82
      (95%CI: 0.78-0.85). Sensitivity analysis showed similar results. No publication
      bias existed (t=0.380, P=0.712). The diagnostic ability of miRNAs were moderate
      for ovarian cancer. Further research was required to obtain accurate results.

PMID- 29029541
TI  - Cancer and the kidney: dangereoux liasons or price paid for the progress in
      medicine?
AB  - A long time ago, the links between renal disease and malignancy were observed,
      however, quite recently, their importance was recognized and 'new' subspecialty
      in nephrology, namely 'onconephrology' was established. In the XXI century,
      patients with malignancy make up the most growing number of the subjects seen for
      nephrology consult and/or critical care nephrology services. A plethora of renal
      problems may be found in patients with malignancy. They may influence not only
      their short-term outcomes but also the adequate therapy of the underlying
      oncological problem. Thus, all these kidney-related issues pose an important
      challenge for both specialities: oncology and nephrology. In the review a
      spectrum of acute and chronic renal injury caused by the malignancy is presented
      as well as the associations between renal disease and cancer. Assessment of
      kidney function and its importance in patients with malignancy is also discussed
      as medical oncologists should check the appropriate dose of chemotherapeutic
      drugs in relation to the actual renal function before prescribing them to the
      patients. Moreover, effects of kidney function on outcomes in oncology is
      presented. In addition, nephrology services should better understand both the
      biology of malignancy with its treatment to become a valuable part treating team
      to yield the best possible outcome. It is important for nephrology services to be
      acknowledged and to take an active participation in care of oncology patients.

PMID- 29029543
TI  - The miR-200 family in ovarian cancer.
AB  - Ovarian cancer (OC) is the most lethal gynecological malignancy. Its insidious
      nature, manifesting with little to no symptoms until the disease progresses to
      metastasis, along with a wide diversity of histological subtypes and
      corresponding clinical behavior, poses significant therapeutic challenges. The
      genetic profiling of this aggressive tumor and its subtypes has led to the
      identification of various molecular markers of prognosis. Among these, the miR
      200 family of miRNAs appears to play an important role. The deregulated
      expression of the miR-200 family members has been detected in a variety of OC
      studies. The present review examines the potential usefulness of the miR-200
      family members as prognostic indicators in ovarian cancer and their impact across
      different OC publications, with a particular focus on prognostic features, such
      as disease stage, tumor histology, survival and response to chemotherapy. We
      present the potential usefulness of the miR-200 family genes as prognostic
      indicators in OC and highlight the tendency that miR-200 overexpression
      corresponds with an advanced cancer stage.

PMID- 29029544
TI  - Melflufen - a peptidase-potentiated alkylating agent in clinical trials.
AB  - Aminopeptidases like aminopeptidase N (APN, also known as CD13) play an important
      role not only in normal cellular functioning but also in the development of
      cancer, including processes like tumor cell invasion, differentiation,
      proliferation, apoptosis, motility, and angiogenesis. An increased expression of
      APN has been described in several types of human malignancies, especially those
      characterized by fast-growing and aggressive phenotypes, suggesting APN as a
      potential therapeutic target. Melphalan flufenamide ethyl ester (melflufen,
      previously denoted J1) is a peptidase-potentiated alkylating agent. Melflufen
      readily penetrates membranes and an equilibrium is rapidly achieved, followed by
      enzymatic cleavage in aminopeptidase positive cells, which results in trapping of
      less lipophilic metabolites. This targeting effect results in very high
      intracellular concentrations of its metabolite melphalan and subsequent apoptotic
      cell death. This results in a potency increase (melflufen vs melphalan) ranging
      from 10- to several 100-fold in different in vitro models. Melflufen triggers a
      rapid, robust, and an irreversible DNA damage which may account for its ability
      to overcome melphalan-resistance in multiple myeloma cells. Furthermore, anti
      angiogenic properties of melflufen have been described. Consequently, it is
      hypothesized that melflufen could provide better efficacy but no more toxicity
      than what is achieved with melphalan, an assumption so far supported by
      experiences from hollow fiber and xenograft studies in rodents as well as by
      clinical data from patients with solid tumors and multiple myeloma. This review
      summarizes the current preclinical and clinical knowledge of melflufen.

PMID- 29029545
TI  - The role of toll-like receptor 4 in tumor microenvironment.
AB  - Tumors are closely related to chronic inflammation, during which there are
      various changes in inflammatory sites, such as immune cells infiltration, pro
      inflammation cytokines production, and interaction between immune cells and
      tissue cells. Besides, substances, released from both tissue cells attacked by
      exogenous etiologies, also act on local cells. These changes induce a dynamic and
      complex microenvironment favorable for tumor growth, invasion, and metastasis.
      The toll-like receptor 4 (TLR4) is the first identified member of the toll-like
      receptor family that can recognize pathogen-associated molecular patterns (PAMPs)
      and damage-associated molecular pattern (DAMPs). TLR4 expresses not only on
      immune cells but also on tumor cells. Accumulating evidences demonstrated that
      the activation of TLR4 in tumor microenvironment can not only boost the anti
      tumor immunity but also give rise to immune surveillance and tumor progression.
      This review will summarize the expression and function of TLR4 on dendritic cells
      (DCs), tumor-associated macrophages (TAMs), T cells, myeloid-derived suppressor
      cells (MDSCs), tumor cells as well as stromal cells in tumor microenvironment.
      Validation of the multiple role of TLR4 in tumors could primarily pave the road
      for the development of anti-tumor immunotherapy.

PMID- 29029546
TI  - Bladder cancer stem cells: clonal origin and therapeutic perspectives.
AB  - In this article, we review the origin and therapeutic perspectives of bladder
      cancer stem cells (BCSCs), which are integral to the initiation, high recurrence
      and chemoresistance of bladder cancer. BCSCs are heterogenous and originate from
      multiple cell types, including urothelial stem cells and differentiated cell
      types, including basal, intermediate stratum and umbrella cells. Cell surface
      markers, including CD44, CD67LR, EMA, ALDH1A1 and BCMab1, are used to identify
      and isolate BCSCs. The Hedgehog, Notch, Wnt and JAK-STAT signaling pathways play
      key roles in maintaining the stemness, self-renewal and proliferative potential
      of BCSCs. High expression of ABC transporters, acetaldehyde dehydrogenase,
      antioxidants and apoptosis resistance proteins in BCSCs play a critical role in
      chemoresistance. Consequently, a greater understanding of the biology of BCSCs
      will be important for identifying effective therapeutic targets to improve
      clinical outcomes for bladder cancer patients.

PMID- 29029547
TI  - Nanoformulations of curcumin: an emerging paradigm for improved remedial
      application.
AB  - Curcumin is a natural polyphenol and essential curcuminoid derived from the
      rhizome of the medicinal plant Curcuma longa (L.) is universally acknowledged as
      "Wonder drug of life". It is a vital consumable and restorative herb, commonly
      keened for several ailments such as cancer, arthritis, pain, bruises,
      gastrointestinal quandaries, swelling and much more. Despite its enormous
      curative potential, the poor aqueous solubility and consequently, minimal
      systemic bioavailability with rapid degradation are some of the major factors
      which restrict the utilization of curcumin at medical perspective. However, to
      improve its clinically relevant parameters, nanoformulation of curcumin is
      emerging as a novel substitute for their superior therapeutic modality. It
      enhances its aqueous solubility and targeted delivery to the tissue of interest
      that prompts to enhance the bioavailability, better drug conveyance, and more
      expeditious treatment. Subsequent investigations are endeavored to enhance the
      bio-distribution of native curcumin by modifying with felicitous nano-carriers
      for encapsulation. In this review, we specifically focus on the recent
      nanotechnology based implementations applied for overcoming the innate
      constraints of native curcumin and additionally the associated challenges which
      restrict its potential therapeutic applications both in vivo and in-vitro
      studies, as well as their detailed mechanism of action, have additionally been
      discussed.

PMID- 29029548
TI  - Antiangiogenic agents after first line and sorafenib plus chemoembolization: a
      systematic review.
AB  - Transarterial chemoembolization (TACE) is the standard treatment for intermediate
      stage, although the combination of TACE with sorafenib may theoretically benefit
      HCC patients in intermediate stage. Owing to the significant antiangiogenic
      effect of sorafenib and the limitation of TACE, it is rational to combine them.
      Though the strategy of combining TACE and sorafenib has been increasingly used in
      patients with unresectable HCC but the current evidence is controversial and its
      clinical role has not been determined yet. In first-line therapy, patients
      receiving sorafenib had increased overall survival and progression free survival.
      Therefore several antiangiogenic agents have entered clinical studies on HCC,
      many with negative results. This review discusses the current drug development
      for patients with HCC and role of TACE plus sorafenib.

PMID- 29029551
TI  - Low Back Pain: Investigation of Biases in Outpatient Canadian Physical Therapy.
AB  - Background: Previous research suggested that physical therapy services can be
      influenced by patient characteristics (age, sex, socioeconomic status) or
      insurance status rather than their clinical need. Objective: The aim of this
      study was to determine whether patient-related factors (age, sex, SES) and the
      source of reimbursement for physical therapy services (insurance status)
      influence wait time for, frequency of, and duration of physical therapy for low
      back pain. Design: This study was an empirical cross-sectional online survey of
      Canadian physical therapy professionals (defined as including physical therapists
      and physical rehabilitation specialists). Methods: A total of 846 physical
      therapy professionals received 1 of 24 different (and randomly selected) clinical
      vignettes (ie, patient case scenarios) and completed a 40-item questionnaire
      about how they would treat the fictional patient in the vignette as well as their
      professional clinical practice. Each vignette described a patient with low back
      pain but with variations in patient characteristics (age, sex, socioeconomic
      status) and insurance status (no insurance, private insurance, Workers'
      Compensation Board insurance). Results: The age, sex, and socioeconomic status of
      the fictional vignette patients did not affect how participants would provide
      service. However, vignette patients with Workers' Compensation Board insurance
      would be seen more frequently than those with private insurance or no insurance.
      When asked explicitly, study participants stated that insurance status, age, and
      chronicity of the condition were not factors associated with wait time for,
      frequency of, or duration of treatment. Limitations: This study used a
      standardized vignette patient and may not accurately represent physical therapy
      professionals' actual clinical practice. Conclusions: There appears to be an
      implicit professional bias in relation to patients' insurance status; the
      resulting inequity in service provision highlights the need for further research
      as a basis for national guidelines to promote equity in access to and provision
      of quality physical therapy services.

PMID- 29029550
TI  - B lymphoblastic leukemia/lymphoma: new insights into genetics, molecular
      aberrations, subclassification and targeted therapy.
AB  - B lymphoblastic leukemia/lymphoma (B-ALL) is a clonal hematopoietic stem cell
      neoplasm derived from B-cell progenitors, which mostly occurs in children and
      adolescents and is regarded as one of top leading causes of death related to
      malignancies in this population. Despite the majority of patients with B-ALL have
      fairly good response to conventional chemotherapeutic interventions followed by
      hematopoietic stem cell transplant for the last decades, a subpopulation of
      patients show chemo-resistance and a high relapse rate. Adult B-ALL exhibits
      similar clinical course but worse prognosis in comparison to younger individuals.
      Ample evidences have shown that the clinical behavior, response rate and clinical
      outcome of B-ALL rely largely on its genetic and molecular profiles, such as the
      presence of BCR-ABL1 fusion gene which is an independent negative prognostic
      predictor. New B-ALL subtypes have been recognized with recurrent genetic
      abnormalities, including B-ALL with intrachromosomal amplification of chromosome
      21 (iAMP21), B-ALL with translocations involving tyrosine kinases or cytokine
      receptors ("BCR-ABL1-like ALL"). Genome-wide genetic profiling studies on B-ALL
      have extended our understanding of genomic landscape of B-ALL, and genetic
      mutations involved in various key pathways have been illustrated. These include
      CRLF2 and PAX5 alterations, TP53, CREBBP and ERG mutations, characteristic
      genetic aberrations in BCR-ABL1-like B-ALL and others. The review further
      provides new insights into clinical implication of the genetic aberrations in
      regard to targeted therapy development.

PMID- 29029552
TI  - Using Rasch Analysis to Validate the Motor Activity Log and the Lower Functioning
      Motor Activity Log in Patients With Stroke.
AB  - Background: The Motor Activity Log (MAL) and Lower-Functioning MAL (LF-MAL) are
      used to assess the amount of use of the more impaired arm and the quality of
      movement during activities in real-life situations for patients with stroke.
      Objective: This study used Rasch analysis to examine the psychometric properties
      of the MAL and LF-MAL in patients with stroke. Design: This is a methodological
      study. Methods: The MAL and LF-MAL include 2 scales: the amount of use (AOU) and
      the quality of movement (QOM). Rasch analysis was used to examine the
      unidimensionality, item difficulty hierarchy, targeting, reliability, and
      differential item functioning (DIF) of the MAL and LF-MAL. Results: A total of
      403 patients with mild or moderate stroke completed the MAL, and 134 patients
      with moderate/severe stroke finished the LF-MAL. Evidence of disordered
      thresholds and poor model fit were found both in the MAL and LF-MAL. After the
      rating categories were collapsed and misfit items were deleted, all items of the
      revised MAL and LF-MAL exhibited ordering and constituted unidimensional
      constructs. The person-item map showed that these assessments were difficult for
      our participants. The person reliability coefficients of these assessments ranged
      from .79 to .87. No items in the revised MAL and LF-MAL exhibited bias related to
      patients' characteristics. Limitations: One limitation is the recruited patients,
      who have relatively high-functioning ability in the LF-MAL. Conclusions: The
      revised MAL and LF-MAL are unidimensional scales and have good reliability. The
      categories function well, and responses to all items in these assessments are not
      biased by patients' characteristics. However, the revised MAL and LF-MAL both
      showed floor effect. Further study might add easy items for assessing the
      performance of activity in real-life situations for patients with stroke.

PMID- 29029549
TI  - Progress and future prospect of in vitro spermatogenesis.
AB  - Infertility has become a major health issue in the world. It affects the social
      life of couples and of all infertility cases; approximately 40-50% is due to
      "male factor" infertility. Male infertility could be due to genetic factors,
      environment or due to gonadotoxic treatment. Developments in reproductive
      biotechnology have made it possible to rescue fertility and uphold biological
      fatherhood. In vitro production of haploid male germ cell is a powerful tool, not
      only for the treatment of infertility including oligozoospermic or azoospermic
      patient, but also for the fertility preservation in pre-pubertal boys whose
      gonadal function is threatened by gonadotoxic therapies. Genomic editing of in
      vitro cultured germ cells could also potentially cure flaws in spermatogenesis
      due to genomic mutation. Furthermore, this ex-vivo maturation technique with
      genomic editing may be used to prevent paternal transmission of genomic diseases.
      Here, we summarize the historical progress of in vitro spermatogenesis research
      by using organ and cell culture techniques and the future clinical application of
      in vitro spermatogenesis.

PMID- 29029553
TI  - Systematic Review of Costs and Effects of Self-Management Interventions for
      Chronic Musculoskeletal Pain: Spotlight on Analytic Perspective and Outcomes
      Assessment.
AB  - Background: Evidence for the cost-effectiveness of self-management interventions
      for chronic musculoskeletal pain (CMP) lacks consensus, which may be due to
      variability in the costing methods employed. Purpose: The purposes of the study
      were to identify how costs and effects have been assessed in economic analysis of
      self-management interventions for CMP and to identify the effect of the chosen
      analytical perspective on cost-effectiveness conclusions. Data Sources: Five
      databases were searched for all study designs using relevant terms. Study
      Selection: Two independent researchers reviewed all titles for predefined
      inclusion criteria: adults (>=18 years of age) with CMP, interventions with a
      primary aim of promoting self-management, and conducted a cost analysis. Data
      Extraction: Descriptive data including population, self-management intervention,
      analytical perspective, and costs and effects measured were collected by one
      reviewer and checked for accuracy by a second reviewer. Data Synthesis: Fifty
      seven studies were identified: 65% (n = 37) chose the societal perspective, of
      which 89% (n = 33) captured health care utilization, 92% (n = 34) reported labor
      productivity, 65% (n = 24) included intervention delivery, and 59% (n = 22)
      captured patient/family costs. Types of costs varied in all studies. Eight
      studies conducted analyses from both health service and societal perspectives;
      cost-effectiveness estimates varied with perspective chosen, but in no case was
      the difference sufficient to change overall policy recommendations. Limitations:
      Chronic musculoskeletal pain conditions where self-management is recommended, but
      not as a primary treatment, were excluded. Gray literature was excluded.
      Conclusion: Substantial heterogeneity in the cost components captured in the
      assessment of self-management for CMP was found; this was independent of the
      analytic perspective used. Greater efforts to ensure complete and consistent
      costings are required if reliable cost-effectiveness evidence of self-management
      interventions is to be generated and to inform the most appropriate perspective
      for economic analyses in this field.

PMID- 29029555
TI  - Turning Over the Hourglass.

PMID- 29029554
TI  - Cross-Sectional Relationships of Physical Activity and Sedentary Behavior With
      Cognitive Function in Older Adults With Probable Mild Cognitive Impairment.
AB  - Background: Mild cognitive impairment (MCI) represents a transition between
      normal cognitive aging and dementia and may represent a critical time frame for
      promoting cognitive health through behavioral strategies. Current evidence
      suggests that physical activity (PA) and sedentary behavior are important for
      cognition. However, it is unclear whether there are differences in PA and
      sedentary behavior between people with probable MCI and people without MCI or
      whether the relationships of PA and sedentary behavior with cognitive function
      differ by MCI status. Objective: The aims of this study were to examine
      differences in PA and sedentary behavior between people with probable MCI and
      people without MCI and whether associations of PA and sedentary behavior with
      cognitive function differed by MCI status. Design: This was a cross-sectional
      study. Methods: Physical activity and sedentary behavior in adults dwelling in
      the community (N = 151; at least 55 years old) were measured using a wrist-worn
      actigraphy unit. The Montreal Cognitive Assessment was used to categorize
      participants with probable MCI (scores of <26/30) and participants without MCI
      (scores of >=26/30). Cognitive function was indexed using the Alzheimer Disease
      Assessment Scale-Cognitive-Plus (ADAS-Cog Plus). Physical activity and sedentary
      behavior were compared based on probable MCI status, and relationships of ADAS
      Cog Plus with PA and sedentary behavior were examined by probable MCI status.
      Results: Participants with probable MCI (n = 82) had lower PA and higher
      sedentary behavior than participants without MCI (n = 69). Higher PA and lower
      sedentary behavior were associated with better ADAS-Cog Plus performance in
      participants without MCI (beta = -.022 and beta = .012, respectively) but not in
      participants with probable MCI (beta < .001 for both). Limitations: This study
      was cross-sectional and therefore could not establish whether conversion to MCI
      attenuated the relationships of PA and sedentary behavior with cognitive
      function. The diagnosis of MCI was not confirmed with a physician; therefore,
      this study could not conclude how many of the participants categorized as having
      probable MCI would actually have been diagnosed with MCI by a physician.
      Conclusions: Participants with probable MCI were less active and more sedentary.
      The relationships of these behaviors with cognitive function differed by MCI
      status; associations were found only in participants without MCI.

PMID- 29029558
TI  - A Bold Vision for Physical Therapy.

PMID- 29029556
TI  - Wheelchair Shuttle Test for Assessing Aerobic Fitness in Youth With Spina Bifida:
      Validity and Reliability.
AB  - Background: Testing aerobic fitness in youth is important because of expected
      relationships with health. Objective: The purpose of the study was to estimate
      the validity and reliability of the Shuttle Ride Test in youth who have spina
      bifida and use a wheelchair for mobility and sport. Design: Ths study is a
      validity and reliability study. Methods: The Shuttle Ride Test, Graded Wheelchair
      Propulsion Test, and skill-related fitness tests were administered to 33
      participants for the validity study (age = 14.5 +/- 3.1 y) and to 28 participants
      for the reliability study (age = 14.7 +/- 3.3 y). Results: No significant
      differences were found between the Graded Wheelchair Propulsion Test and the
      Shuttle Ride Test for most cardiorespiratory responses. Correlations between the
      Graded Wheelchair Propulsion Test and the Shuttle Ride Test were moderate to high
      (r = .55-.97). The variance in peak oxygen uptake (VO2peak) could be predicted
      for 77% of the participants by height, number of shuttles completed, and weight,
      with large prediction intervals. High correlations were found between number of
      shuttles completed and skill-related fitness tests (CI = .73 to -.92). Intraclass
      correlation coefficients were high (.77-.98), with a smallest detectable change
      of 1.5 for number of shuttles completed and with coefficients of variation of
      6.2% and 6.4% for absolute VO2peak and relative VO2peak, respectively.
      Conclusions: When measuring VO2peak directly by using a mobile gas analysis
      system, the Shuttle Ride Test is highly valid for testing VO2peak in youth who
      have spina bifida and use a wheelchair for mobility and sport. The outcome
      measure of number of shuttles represents aerobic fitness and is also highly
      correlated with both anaerobic performance and agility. It is not possible to
      predict VO2peak accurately by using the number of shuttles completed. Moreover,
      the Shuttle Ride Test is highly reliable in youth with spina bifida, with a good
      smallest detectable change for the number of shuttles completed.

PMID- 29029559
TI  - Congratulations to the 2017 PODS and NIFTI Recipients.

PMID- 29029557
TI  - Do Exercise Interventions Improve Participation in Life Roles in Older Adults? A
      Systematic Review and Meta-Analysis.
AB  - Background: The World Health Organization recognizes participation in meaningful
      life roles as a key component of health. However, the evidence base for
      interventions to improve participation remains inconclusive. In particular,
      whether exercise interventions improve participation in life roles is unclear.
      Purpose: The aim of this review was to evaluate the effect of physical exercise
      interventions on participation in life roles in older adults residing in the
      community. Data sources: The PubMed, Embase, CINAHL, Cochrane, and PEDro
      databases were searched from inception through March 2015. Study selection:
      Randomized controlled trials comparing the effects of an exercise intervention to
      usual care on participation in life roles in adults who were 60 years of age or
      older were included in this review. Data extraction: Teams of 2 investigators
      independently extracted data on participation. Methodological quality was
      appraised using the Cochrane tool for assessing the risk of bias. The protocol
      was registered with Prospero (CRD42014014880). Data synthesis: Eighteen
      randomized controlled trials with a total of 2,315 participants met the inclusion
      criteria. Standardized mean differences (SMDs) with 95% CIs were calculated using
      a random-effects model. A meta-analysis of 16 studies showed no overall effect of
      the exercise interventions on participation (SMD = 0.03; 95% CI = -0.10 to 0.16).
      Subgroup analysis showed that exercise interventions lasting 12 months or more
      had a small positive effect on participation (SMD = 0.15; 95% CI = 0.02 to 0.28).
      Limitations: Limitations included variability in definitions and measures of
      participation. Conclusions: In general, exercise interventions do not improve
      participation in life roles in older adults. The results do not support the
      implicit assumption that exercise-based interventions associated with improved
      function/activity also result in improved participation. Investigation of complex
      interventions that go beyond exercise to address participation in life roles for
      older adults is warranted.

PMID- 29029562
TI  - The Role of Emotion Regulation and Socialization in Behavioral Parent Training: A
      Proof-of-Concept Study.
AB  - Low-income families are less likely to effectively engage in Behavioral Parent
      Training (BPT), the standard of care for early-onset (3-8 years old) disruptive
      behavior disorders (DBDs); however, relatively little is known about predictors
      of treatment process and outcome within this vulnerable group. Given literature
      to suggest compromises associated with both low-income status and DBDs, this
      study examined the role of caregiver emotion regulation and socialization
      practices in 15 low-income families who participated in one evidence-based BPT
      program, Helping the Noncompliant Child (HNC). Findings suggest baseline
      caregiver emotion regulation predicted variability in BPT treatment duration and
      outcomes, whereas baseline caregiver emotion socialization practices explained
      variation in the severity of child disruptive behaviors concurrently, as well as
      BPT treatment outcomes. Furthermore, BPT yielded pre- to posttreatment effect
      sizes that were equivalent to or better than treatments designed to more
      explicitly target emotion regulation and socialization processes. Clinical
      implications and future directions are discussed.

PMID- 29029563
TI  - Development of a Single-Session, Transdiagnostic Preventive Intervention for
      Young Adults at Risk for Emotional Disorders.
AB  - Cognitive-behavioral prevention programs have demonstrated efficacy in reducing
      subclinical symptoms of anxiety and depression, and there is some evidence to
      suggest that they can lower the risk of future disorder onset. However, existing
      interventions tend to be relatively lengthy and target specific disorders or
      problem areas, both of which limit their potential for widespread dissemination.
      To address these limitations, we aimed to develop a single-session,
      transdiagnostic preventive intervention based on the Unified Protocol for
      Transdiagnostic Treatment of Emotional Disorders for young adults at risk for
      developing anxiety and/or depressive disorders within a college setting. Results
      from this proof-of-concept study indicated that the intervention was viewed as
      highly satisfactory and acceptable. The intervention also was successful at
      delivering adaptive emotion management skills in its 2-hr workshop format. Future
      studies evaluating the efficacy of this novel transdiagnostic, emotion-focused
      prevention program are warranted.

PMID- 29029560
TI  - Failure and Redemption of Statistical and Nonstatistical Rate Theories in the
      Hydroboration of Alkenes.
AB  - Our previous work found that canonical forms of transition state theory
      incorrectly predict the regioselectivity of the hydroboration of propene with BH3
      in solution. In response, it has been suggested that alternative statistical and
      nonstatistical rate theories can adequately account for the selectivity. This
      paper uses a combination of experimental and theoretical studies to critically
      evaluate the ability of these rate theories, as well as dynamic trajectories and
      newly developed localized statistical models, to predict quantitative
      selectivities and qualitative trends in hydroborations on a broader scale. The
      hydroboration of a series of terminally substituted alkenes with BH3 was examined
      experimentally, and a classically unexpected trend is that the selectivity
      increases as the alkyl chain is lengthened far from the reactive centers.
      Conventional and variational transition state theories can predict neither the
      selectivities nor the trends. The canonical competitive nonstatistical model
      makes somewhat better predictions for some alkenes but fails to predict trends,
      and it performs poorly with an alkene chosen to test a specific prediction of the
      model. Added nonstatistical corrections to this model make the predictions worse.
      Parametrized Rice-Ramsperger-Kassel-Marcus (RRKM)-master equation calculations
      correctly predict the direction of the trend in selectivity versus alkene size
      but overpredict its magnitude, and the selectivity with large alkenes remains
      unpredictable with any parametrization. Trajectory studies in explicit solvent
      can predict selectivities without parametrization but are impractical for
      predicting small changes in selectivity. From a lifetime and energy analysis of
      the trajectories, "localized RRKM-ME" and "competitive localized noncanonical"
      rate models are suggested as steps toward a general model. These provide the best
      predictions of the experimental observations and insight into the selectivities.

PMID- 29029561
TI  - Women with PSVT are often misdiagnosed, referred later than men, and have more
      symptoms after ablation.
AB  - OBJECTIVES: Using a patient and gender perspective, this study evaluates the
      experiences and perspectives of referral for paroxysmal supraventricular
      tachycardia (PSVT), and symptoms, Health-Related Quality of Life (HRQOL) and
      functional impairment before and six months after ablation. DESIGN: This
      prospective study includes 214 (109 women) patients with PSVT who completed
      questionnaires before and after ablation addressing referral patterns, duration
      of arrhythmia, socioeconomic status, symptoms, HRQOL, and functional impairment.
      RESULT: Women had a longer history of symptomatic arrhythmia before ablation
      compared to men (16.2 +/- 14.6 vs. 9.9 +/- 13.1 years, p = .001). From the
      patient's perspective, physicians more often incorrectly interpreted women's
      symptoms as anxiety, stress, panic attacks, or depression compared to men,
      delaying referral for ablation. More women than men stated they were not taken
      seriously when consulting for their tachycardia symptoms (17% vs.7%, p = .03). At
      baseline, there were minor differences between the sexes in HRQOL and functional
      impairment, but women had a higher symptom score on Symptoms Checklist Frequency
      (19 vs. 14, p < .001) and Severity Scale (12 vs. 16, p = .001). At six months,
      women were more symptomatic and their HRQOL improved less than in men. Both sexes
      reported improvement in recreation and pastime (p = .001). CONCLUSION: Women with
      PSVT are referred for ablation later, and are more symptomatic before and after
      ablation than men. Symptoms due to PSVT are often incorrectly diagnosed as panic
      attacks, stress, anxiety, or depression, misdiagnoses that delay referral for
      ablation, especially for women.

PMID- 29029564
TI  - Psychometric Validation of the Revised Child Anxiety and Depression Scales-Parent
      Version (RCADS-P) in Children Evaluated for ADHD.
AB  - Children with attention-deficit/hyperactivity disorder (ADHD) frequently
      experience comorbid internalizing symptoms. The Revised Child Anxiety and
      Depression Scales-Parent Version (RCADS-P) is a frequently used measure of
      anxiety and depression in children, though its psychometric properties remain
      unexamined in children referred for ADHD specifically. The present study
      evaluated the RCADS-P in 372 children (age 7-12 years; 68% male) referred for
      evaluation at an ADHD specialty clinic (89% met criteria for ADHD). In addition
      to the RCADS-P, parents completed the Vanderbilt ADHD Diagnostic Rating Scale and
      Child Behavior Checklist and were administered the Kiddie Schedule for Affective
      Disorders and Schizophrenia for School-Age Children semistructured diagnostic
      interview. Teacher ratings were available for approximately half of the sample.
      Factor structure, reliability, convergent/discriminant validity, and
      sensitivity/specificity were examined. Results supported the six-factor structure
      of the RCADS-P. The RCADS-P demonstrated adequate internal consistency as well as
      convergent and discriminant validity with other parent ratings and, to a somewhat
      lesser extent, teacher ratings. Children with an internalizing diagnosis had
      higher RCADS-P scores than children without an internalizing diagnosis. Finally,
      the RCADS-P had good-to-excellent diagnostic efficiency, and a total sum score of
      25 had excellent sensitivity and fair specificity. Findings provide psychometric
      support for the RCADS-P in children with ADHD.

PMID- 29029566
TI  - Associations Among Quadriceps Strength and Rate of Torque Development 6 Weeks
      Post Anterior Cruciate Ligament Reconstruction and Future Hop and Vertical Jump
      Performance: A Prospective Cohort Study.
AB  - Study Design Prospective cohort. Background Quadriceps strength is associated
      with hop distance and jump height in persons who have undergone anterior cruciate
      ligament (ACL) reconstruction. However, it is unknown whether the ability to
      rapidly generate quadriceps torque in the early phase of recovery is associated
      with future hopping and jumping performance in this population. Objective To
      evaluate the prospective associations among quadriceps strength and rate of
      torque development (RTD) and single-leg hop for distance, vertical jump height,
      vertical ground reaction force (vGRF), and vertical force loading rate during a
      landing task in persons who have undergone ACL reconstruction. Methods Seventy
      patients with unilateral ACL reconstruction participated. At 6 weeks post ACL
      reconstruction, isometric quadriceps strength and RTD were measured using a
      dynamometer. At 6 months following ACL reconstruction, patients performed the
      single-leg hop for distance test. Patients also performed the single-leg vertical
      jump test on a force plate that measured maximum jump height, vGRF, and average
      loading rate during landing. Results Both quadriceps strength and RTD at 6 weeks
      post ACL reconstruction were associated with all hopping and jumping measures at
      6 months post ACL reconstruction (P<=.04). Single-leg hop distance was associated
      more closely with quadriceps strength than with quadriceps RTD (P = .05), and
      vertical jump height and vGRF measures were associated more closely with
      quadriceps RTD than with quadriceps strength (P = .05 and P<.01, respectively).
      Both quadriceps measures were associated with loading rate. Conclusion Quadriceps
      strength and RTD are complementary but distinct predictors of future hopping and
      jumping performance in persons who have undergone ACL reconstruction. These
      findings may contribute to improved rehabilitation of patients who are at risk
      for poor jumping/hopping performance and abnormal knee loading. J Orthop Sports
      Phys Ther 2017;47(11):845-852. Epub 13 Oct 2017. doi:10.2519/jospt.2017.7133.

PMID- 29029567
TI  - More than 20 years' experience of left ventricular assist device implantation at
      a non-transplant Centre.
AB  - OBJECTIVES: Over recent decades implantable left ventricular assist devices
      (LVAD) have increased the possibility of improved survival in patients with
      advanced heart failure who also benefit from a better quality of life. The aim of
      this retrospective survey was to review the clinical results of LVAD implantation
      at a low-volume non-transplant centre (Linkoping, Sweden) between 1993 and 2016.
      Our aim was also to assess the mortality and morbidity rates associated with
      implantation of three LVAD versions at our centre, and to compare our results
      with those from transplant centres. DESIGN: A retrospective cohort study was
      performed examining the medical records of patients who had a HeartMate(r) (HMI,
      HMII, HMIII) LVAD implanted as a bridge to heart transplantation (BTT) or as
      destination therapy (DT) at the University Hospital, Linkoping. RESULTS: Our main
      finding was a survival to heart transplantation rate of 82% among our BTT LVAD
      patients. The most common adverse event among our patients was infection. A
      higher frequency of temporary dialysis was seen in the HMII group compared to the
      HMI group, and the frequency of right ventricular failure was higher in our HMII
      material. CONCLUSIONS: Our data suggests that patients requiring long-term LVAD
      support can safely have their device implanted and cared for at a non-transplant
      centre.

PMID- 29029568
TI  - Quaternized chitosan nanoparticles loaded with the combined attenuated live
      vaccine against Newcastle disease and infectious bronchitis elicit immune
      response in chicken after intranasal administration.
AB  - Newcastle disease (ND) and infectious bronchitis (IB) are important diseases,
      which cause respiratory diseases in chickens, resulting in severely economic
      losses in the poultry industry. In this study, N-2-hydroxypropyl trimethyl
      ammonium chloride chitosan (N-2-HACC) and N,O-carboxymethyl chitosan (CMC) were
      synthesized as adjuvant and delivery carrier for vaccine antigens. N-2-HACC
      CMC/NDV/IBV nanoparticles (NPs) (NDV/La Sota and IBV/H120 encapsulated in N-2
      HACC-CMC NPs) and N-2-HACC-CMC/NDV-IBV NPs (the mixing of N-2-HACC-CMC/NDV NPs
      and N-2-HACC-CMC/IBV NPs in a ratio of 1:1) were prepared by the polyelectrolyte
      composite method, respectively. Both nanoparticles exhibited lower cytotoxicity
      and higher stability. Their bioactivities were maintained when they were stored
      at 37  degrees C for three weeks. Release assay in vitro showed that both NDV and
      IBV could be sustainably released from the nanoparticles after an initial burst
      release. In vivo immunization of chickens showed that N-2-HACC-CMC/NDV/IBV NPs or
      N-2-HACC-CMC/NDV-IBV NPs intranasally induced higher titers of IgG and IgA
      antibodies, significantly promoted proliferation of lymphocytes and induced
      higher levels of interleukine-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma)
      than the commercially combined attenuated live vaccine did. This is the first
      study in the field of animal vaccines demonstrating that intranasal
      administration of chickens with antigens (NDV and IBV) encapsulated with chitosan
      derivative could induce humoral, cellular, and mucosal immune responses, which
      protected chickens from the infection of highly virulent NDV and IBV. This study
      indicated that N-2-HACC-CMC could be used as an efficient adjuvant and delivery
      carrier for further development of mucosal vaccines and drugs and could have an
      immense application potential in medicine.

PMID- 29029569
TI  - Friendship Quality in Adolescents With ADHD.
AB  - OBJECTIVE: This study compared the quality of friendships (same- and other-sex)
      in adolescents with and without ADHD, across age and gender. METHOD: A community
      sample of 115 participants (61 ADHD, 54 Comparison), ages 13 to 18, completed a
      questionnaire assessing perceived levels of social support and negative
      interactions experienced in their friendships. RESULTS: Ratings of friendship
      social support diminished across age in youth with ADHD, but increased in
      typically developing youth. Adolescents with and without ADHD, however, did not
      differ on ratings of negative interactions experienced in their friendships.
      Compared with males, females rated their friendships to be more supportive,
      irrespective of ADHD status. Adolescents with and without ADHD rated their same
      sex friendships to be simultaneously more supportive and more conflictual than
      their other-sex friendships. CONCLUSION: Assessments of adolescents with ADHD
      should include a careful examination of their social functioning with particular
      attention devoted to the quality of their friendships.

PMID- 29029570
TI  - Clinical characteristics of poly-drug abuse among heroin dependents and
      association with other psychopathology in compulsory isolation treatment settings
      in China.
AB  - OBJECTIVE: To investigate clinical characteristics and associations of polydrug
      abuse among heroin-dependent patients in compulsory isolation settings in China.
      METHODS: Structured interviews were conducted in 882 heroin-dependent patients in
      two compulsory isolation settings in Changsha, China. Descriptive statistics were
      employed to report prevalence and general information of polydrug abuse among the
      participants. Bivariate associations were examined between polydrug abuse and
      variables regarding demographics, heroin use profile and psychopathology.
      Multivariate logistic regressions were conducted to determine independent factors
      associated with polydrug abuse. RESULTS: Of all the participants, 40.6% reported
      abuse of/dependence on at least one other type of drug/alcohol than
      heroin/opioids during the month preceding admission, with benzodiazepines and
      alcohol being the most common type of drugs abused apart from heroin. Antisocial
      and depressive personality disorders, as well as more severe heroin use patterns,
      including younger age at initiate use and larger amount used per day, were found
      to be independently associated with polydrug abuse. CONCLUSIONS: The prevalence
      of polydrug abuse and its associated severe heroin use patterns and personality
      disorders suggests an urgent need of promoting treatment policies and strategies
      for heroin patients in China to address these issues.

PMID- 29029572
TI  - Response to: The death of ward-based learning.

PMID- 29029573
TI  - "Time and space". a further development in consent for elective spinal
      neurosurgery.

PMID- 29029574
TI  - Early Postoperative Infection Following Open Reduction Internal Fixation Repair
      of Closed Malleolar Fractures.
AB  - BACKGROUND: Early postoperative infection (EPI) following hardware placement in
      patients with malleolar fractures is a serious complication. Identifying factors
      that place patients at risk for early infection may help target interventions to
      prevent infections. METHODS: Data for the study included all adult patients who
      underwent operative management for closed malleolar fracture from 2006 to 2013 in
      the National Surgical Quality Improvement Program database. Characteristics of
      patients with and without EPI were compared using univariate tests. Logistic
      regression was used to perform a multivariable analysis of risk factors for EPI
      while controlling for covariates. Length of stay was analyzed using a generalized
      linear model. RESULTS: The analysis sample included 7054 patients, of whom 116
      developed EPI. Patients with EPI were slightly older on average, more likely to
      have diabetes, and had higher anesthesia class. Multivariable analysis identified
      several risk factors for EPI, including diabetes (odds ratio [OR] = 2.6; 95% CI =
      1.5-4.5; P < .0001), American Society of Anaesthesiology (ASA) class 3+ (OR =
      2.3; 95% CI = 1.03-5.0; P = .04), unclean surgery (OR = 2.4; 95% CI = 1.3-4.2; P
      < .0001), and inpatient location (OR 1.7, 1.1-2.7; P = .01). After controlling
      for other factors, EPI was not significantly associated with a longer hospital
      stay (0.2 days, P = .55). CONCLUSION: In the 30 days after hardware placement for
      malleolar fracture, infection occurs with increased frequency in older patients,
      diabetics, those with higher anesthesia class, and in the setting of unclean
      surgery and inpatient operative location. Patients with the identified risk
      factors should be followed closely for development of infection. LEVELS OF
      EVIDENCE: Level III: Retrospective cohort study.

PMID- 29029571
TI  - Encoding strategy training and self-reported everyday prospective memory in
      people with Parkinson disease: a randomized-controlled trial.
AB  - Objective To compare the effects of laboratory-based training in implementation
      intentions (II; experimental strategy) and verbal rehearsal (VR; control
      strategy) on self-reported everyday prospective memory among people with
      Parkinson disease (PD) and to investigate potential correlates of change in self
      reported everyday prospective memory in response to this training. Method This
      was a randomized-controlled trial. Participants with mild to moderate PD without
      dementia underwent one session of training in either II (n = 25) or VR (n = 27).
      Then they were instructed to use their strategy as much as possible in their
      everyday lives to help them remember to do things. The Prospective and
      Retrospective Memory Questionnaire Prospective Scale (PRMQ-Pro) administered at
      baseline and one month after training assessed training-related change in self
      reported everyday prospective memory. Baseline depressive symptoms, perceptions
      of the strategy (credibility, expectancy), prospective memory-related awareness,
      global cognition, and disease severity were correlated to PRMQ-Pro Change scores
      (post minus pre) to determine their association with response to training.
      Results The VR group's PRMQ-Pro scores declined from pre to post training, while
      the II group's remained stable (p = .03). This effect was driven by change in
      self-cued everyday prospective memory tasks. Higher baseline depressive symptoms,
      treatment expectancy, and global cognition related to better response to training
      in the II group (rs <= -.40, ps <= .05). Conclusions II training may prevent
      everyday prospective memory decline among people with PD. In addition, people
      with higher depression, stronger expectations of improvement from strategy
      training, or better global cognition may benefit the most from II training.

PMID- 29029575
TI  - Effect of Gender on Mechanical Properties of the Plantar Fascia and Heel Fat Pad.
AB  - BACKGROUND: The purpose of the study was to investigate the plantar fascia and
      heel fat pad stiffness and thickness parameters in females and compare these
      values with those of males. METHODS: This study was carried out in 60 healthy
      sedentary participants (30 female, 30 male) between the ages of 19 and 50 years.
      Shear wave velocity (SWV) and thickness of the plantar fascia and heel fat pad
      were measured with an ultrasonography device. RESULTS: Males had a higher plantar
      fascia ( P = .037) and heel fat pad ( P = .001) thickness compared with females,
      but SWV of the plantar fascia ( P = .673), heel fat pad microchamber layer ( P =
      .240), and heel fat pad macrochamber layer ( P = .636) were similar in both
      groups. Body mass had a strong correlation with the plantar fascia ( r = 0.64, P
      < .001) and heel fat pad thickness ( r = 0.68, P < .001). Height had a moderate
      correlation with the plantar fascia ( r = 0.44, P < .001) and heel fat pad
      thickness ( r = 0.42, P = .001). CONCLUSION: Plantar fascia and heel fat pad
      stiffness were similar in both genders; however, females had a lower plantar
      fascia and heel fat pad thickness compared with males. Correlation analysis
      results suggest that higher plantar fascia and heel fat pad thickness in males
      may be related to higher body mass and height. LEVELS OF EVIDENCE: Level III:
      Retrospective comparative study.

PMID- 29029576
TI  - Marine Aerosols and Clouds.
AB  - The role of marine bioaerosols in cloud formation and climate is currently so
      uncertain that even the sign of the climate forcing is unclear. Marine aerosols
      form through direct emissions and through the conversion of gas-phase emissions
      to aerosols in the atmosphere. The composition and size of aerosols determine how
      effective they are in catalyzing the formation of water droplets and ice crystals
      in clouds by acting as cloud condensation nuclei and ice nucleating particles,
      respectively. Marine organic aerosols may be sourced both from recent regional
      phytoplankton blooms that add labile organic matter to the surface ocean and from
      long-term global processes, such as the upwelling of old refractory dissolved
      organic matter from the deep ocean. Understanding the formation of marine
      aerosols and their propensity to catalyze cloud formation processes are
      challenges that must be addressed given the major uncertainties associated with
      aerosols in climate models.

PMID- 29029578
TI  - The empathy test.

PMID- 29029577
TI  - A novel core-shell lipid nanoparticle for improving oral administration of water
      soluble chemotherapeutic agents: inhibited intestinal hydrolysis and enhanced
      lymphatic absorption.
AB  - The oral administration of water-soluble chemotherapeutical agents is limited by
      their serious gastrointestinal side effects, instability at intestinal pH, and
      poor absorption. Aiming to solve these problems, we chose topotecan (TPT) as a
      model drug and developed a novel lipid formulation containing core-shell lipid
      nanoparticle (CLN) that makes the water-soluble drug to 'dissolve' in oil. TPT
      molecules can be encapsulated into nanoparticles surrounded by oil barrier while
      avoiding the direct contact with intestinal environment, thus easing the
      intestinal hydrolytic degradation and gastrointestinal (GI) irritation.
      Microstructure and mean particle size of TPT-CLN were characterized by
      Transmission Electron Microscope (TEM) and Dynamic Light Scattering (DLS),
      respectively. The average size of nanoparticles was approximately 60 nm with a
      homogeneous distribution in shapes of spheres or ellipsoid. According to in vitro
      stability studies, more initial form of TPT was observed in presence of lipid
      nanoparticle compared with free topotecan solution in artificial intestinal juice
      (pH 6.5). After oral administration of TPT-CLN in rats, AUC and Cmax of TPT were
      all increased compared with free TPT, indicating significant enhancement of oral
      absorption. Intestinal lymphatic transport was confirmed as the major way for CLN
      to enhance oral absorption of TPT by the treatment of blocking chylomicron flow.
      Lower GI irritation of TPT-CLN was observed in the gastrointestinal damage
      studies. The in vivo antitumor activity of TPT-CLN showed an improved antitumor
      efficacy by oral treatment of TPT-CLN compared to free TPT. From the obtained
      data, the systems appear an attractive progress in oral administration of
      topotecan.

PMID- 29029579
TI  - Fatigue - but not mTBI history, PTSD, or sleep quality - directly contributes to
      reduced prospective memory performance in Iraq and Afghanistan era Veterans.
AB  - OBJECTIVE: Memory problems that affect daily functioning are a frequent complaint
      among Veterans reporting a history of repetitive mild traumatic brain injury
      (mTBI), especially in cohorts with comorbid PTSD. Here, we test the degree to
      which subjective sleep impairment and daytime fatigue account for the association
      of PTSD and self-reported mTBI history with prospective memory. METHOD: 82
      Veterans with and without personal history of repeated blast-related mTBI during
      deployment were administered the Clinician Administered PTSD Scale (CAPS), Memory
      for Intentions Test (MIST), Patient Health Questionnaire-9 (PHQ-9),
      Neurobehavioral Symptom Inventory (NSI), and the Pittsburgh Sleep Quality Index
      (PSQI). Relationships between self-reported mTBI, PTSD, self-reported poor sleep
      and daytime fatigue, and MIST performance were modeled using partial least
      squares structural equation modeling (PLS-SEM). RESULTS: Reported daytime fatigue
      was strongly associated with poorer prospective memory performance. Poor
      subjective sleep quality was strongly and positively associated with reported
      daytime fatigue, but had no significant direct effect on prospective memory
      performance. PTSD diagnosis and self-reported mTBI history were only associated
      with prospective memory via their impact on subjective sleep quality and daytime
      fatigue. CONCLUSIONS: Results suggest that daytime fatigue may be a mediating
      factor by which both mTBI and PTSD can interfere with prospective memory.
      Additional attention should be given to complaints of daytime fatigue,
      independent of subjective sleep quality, in the clinical care of those with a
      self-reported history of mTBI, and/or PTSD. Further research into whether
      interventions that decrease daytime fatigue lead to improvement in prospective
      memory and subjective cognitive functioning is warranted.

PMID- 29029580
TI  - Uncovering Longitudinal Health Care Behaviors for Millions of Medicaid Enrollees:
      A Multistate Comparison of Pediatric Asthma Utilization.
AB  - BACKGROUND: This study introduces a framework for analyzing and visualizing
      health care utilization for millions of children, with a focus on pediatric
      asthma, one of the major chronic respiratory conditions. METHODS: The data source
      is the 2005 to 2012 Medicaid Analytic Extract claims for 10 Southeast states. The
      study population consists of Medicaid-enrolled children with persistent asthma.
      We translate multiyear, individual-level medical claims into sequences of
      discrete utilization events, which are modeled using Markov renewal processes and
      model-based clustering. Network analysis is used to visualize utilization
      profiles. The method is general, allowing the study of other chronic conditions.
      RESULTS: The study population consists of 1.5 million children with persistent
      asthma. All states have profiles with high probability of asthma controller
      medication, as large as 60.6% to 90.2% of the state study population. The
      probability of consecutive asthma controller prescriptions ranges between 0.75
      and 0.95. All states have utilization profiles with uncontrolled asthma with 4.5%
      to 22.9% of the state study population. The probability for controller medication
      is larger than for short-term medication after a physician visit but not after an
      emergency department (ED) visit or hospitalization. Transitions from ED or
      hospitalization generally have a lower probability into physician office (between
      0.11 and 0.38) than into ED or hospitalization (between 0.20 and 0.59).
      CONCLUSIONS: In most profiles, children who take asthma controller medication do
      so regularly. Follow-up physician office visits after an ED encounter or
      hospitalization are observed at a low rate across all states. Finally, all states
      have a proportion of children who have uncontrolled asthma, meaning they do not
      take controller medication while they have severe outcomes.

PMID- 29029581
TI  - Prevalence of urinary tract infections mimicking respiratory infections and risk
      factors associated.

PMID- 29029582
TI  - New Concepts in the Treatment of Malignant Pleural Mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is a highly aggressive and generally
      incurable cancer. Current anti-MPM chemotherapy-based treatments are only
      marginally effective, and long-term survival remains an unmet goal. Nonetheless,
      in selected cases, personalized surgery-based multimodality treatments (MMT) have
      been shown to significantly extend survival. The design of MMT and selection of
      patients are challenging, and optimal results require accurate presurgical
      diagnosis, staging, and risk stratification. Further, meticulous surgical
      techniques and advanced radiation protocols must be applied. We review key
      principles and evolving concepts in the care of MPM patients with a focus on the
      expanding role of MMT in MPM.

PMID- 29029583
TI  - New-Generation High-Potency and Designer Antibodies: Role in HIV-1 Treatment.
AB  - Broadly neutralizing antibodies (bNAbs) have been evaluated as promising agents
      in the fight against infectious diseases. HIV-1-specific bNAbs, in particular,
      have been tested in both preventive and therapeutic modalities. Multiple bNAbs
      have been isolated, characterized, and assessed in vitro and in vivo, but no
      single antibody appears to possess the breadth and potency that may be needed if
      it is to be used in the treatment of HIV-1 infection. With the technological
      advances of the past decades, novel and more effective bNAbs have been identified
      or engineered for higher neutralizing potency, greater breadth, and increased
      serum half-life. In this review, we discuss the development of a new generation
      of anti-HIV-1 bNAbs and their potential to be used clinically for treatment and
      prevention of HIV-1 infection.

PMID- 29029584
TI  - Evidence for Genetic Risk Contributing to Long-Term Adverse Treatment Effects in
      Childhood Cancer Survivors.
AB  - Survivors of childhood cancer are at increased risk for therapy-related
      morbidities and mortality. Although the demographic and clinical factors
      predicting the risk for long-term effects of cancer therapy are well known, the
      impact of genetic risk for specific late effects is less clearly defined. Here,
      we review the extant literature and recent research describing genetic modifiers
      to risk for the more common late effects of childhood cancer therapy. Results of
      this research support the need for clinical trials that attempt to further refine
      risk prediction by incorporating genetic testing into existing algorithms that
      are primarily based on clinical and demographic factors. Confirmation of genetic
      predisposition, as defined by reproducibility and prospective validation, would
      permit therapeutic modification and discussion of individualized survivor care
      plans even at initial cancer diagnosis.

PMID- 29029585
TI  - Refinement of the Affordable Care Act: A Progressive Perspective.
AB  - The Affordable Care Act (ACA) was the most significant expansion of health
      coverage since Medicare and Medicaid were enacted. The law resulted in
      approximately 13-20 million uninsured persons gaining coverage. Despite these
      gains, the ACA has numerous shortcomings. For progressives, the ACA was a unique
      opportunity to provide access to high-quality, comprehensive, equitable health
      coverage to all persons living in the United States. Using this perspective as
      our framework, in this review we highlight some of the limitations of the ACA and
      potential areas for refinement. We conclude that the ACA fell far short of the
      goal of achieving universal coverage and that the coverage made available through
      the ACA was not equitable. In addition, the ACA expanded coverage by building
      onto a highly fragmented, inefficient, and costly health system. Thus, it did
      little to control health costs. A more fiscally prudent approach would have been
      built upon more successful existing programs, such as a Medicare for All.

PMID- 29029586
TI  - Use and Misuse of Opioids in Chronic Pain.
AB  - The prescribing of opioid analgesics for pain management-particularly for
      management of chronic noncancer pain (CNCP)-has increased more than fourfold in
      the United States since the mid-1990s. Yet there is mounting evidence that
      opioids have only limited effectiveness in the management of CNCP, and the
      increased availability of prescribed opioids has contributed to upsurges in
      opioid-related addiction cases and overdose deaths. These concerns have led to
      critical revisiting and modification of prior pain management practices (e.g.,
      guidelines from the Centers for Disease Control and Prevention), but the much
      needed changes in clinical practice will be facilitated by a better understanding
      of the pharmacology and behavioral effects of opioids that underlie both their
      therapeutic effects (analgesia) and their adverse effects (addiction and
      overdose). With these goals in mind, this review first presents an overview of
      the contemporary problems associated with opioid management of CNCP and the
      related public health issues of opioid diversion, overdose, and addiction. It
      then discusses the pharmacology underlying the therapeutic and main adverse
      effects of opioids and its implications for clinical management of CNCP within
      the framework of recent clinical guidelines for prescribing opioids in the
      management of CNCP.

PMID- 29029587
TI  - "Here if you need me": exploring peer support to enhance access to physical
      health care.
AB  - BACKGROUND: People diagnosed with mental illness (hereinafter "consumers") have
      higher rates of chronic disease and significantly shorter lives than the wider
      population. Peer workers have become increasingly involved in facilitating access
      to physical health care, yet the consumer perspective regarding peer involvement
      is unknown. This absent voice is needed to inform strategic planning and generate
      solutions to address the current inequity in health status. AIM: To articulate
      the views of consumers in regards to the potential use of peer workers to further
      the physical health of people with mental illness. METHODS: A qualitative
      exploratory study was conducted involving four focus groups with 31 consumer
      participants. Focus group responses were analysed thematically. RESULTS: Three
      themes pertaining to enhancing physical health care emerged: (1) the potential of
      peer workers in mitigating existing barriers, (2) consumer advocacy organisations
      expanding their agenda and (3) benefits of segregated activities as a segue to
      mainstream options. CONCLUSIONS: The envisaged forms of peer contribution have
      far greater scope and depth than is currently considered in policy, the research
      literature and health practice. Innovative solutions are required for this
      neglected population. Individual and systemic advocacy led by peer workers can
      enhance access to physical health care and have the potential to reduce physical
      health inequalities.

PMID- 29029588
TI  - Society for the Advancement of Transplant Anesthesia: Liver Transplant Anesthesia
      Fellowship-White Paper Advocating Measurable Proficiency in Transplant
      Specialties Training.
AB  - The anesthesia community has openly debated if the care of transplant patients
      was generalist or specialist care ever since the publication of an opinion paper
      in 1999 recommended subspecialty training in the field of liver transplantation
      anesthesia. In the past decade, liver transplant anesthesia has become more
      complex with a sicker patient population and evolving evidence-based practices.
      Transplant training is currently not required for accreditation or certification
      in anesthesiology, and not all anesthesia residency programs are associated with
      transplant centers. Yet there is evidence that patient outcome is affected by the
      experience of the anesthesiologist with liver transplants as part of a
      multidisciplinary care team. Requests for a formal review of the inequities in
      training opportunities and requirements led the Society for the Advancement for
      Transplant Anesthesia (SATA) to begin the task of developing post-graduate
      fellowship training recommendations. In this article, members of the SATA Working
      Group on Transplant Anesthesia Education present their reasoning for specialized
      education and conclusions about which pathways can better prepare trainees to
      care for complex transplant patients.

PMID- 29029589
TI  - Environmental Adaptations, Ecological Filtering, and Dispersal Central to Insect
      Invasions.
AB  - Insect invasions, the establishment and spread of nonnative insects in new
      regions, can have extensive economic and environmental consequences. Increased
      global connectivity accelerates rates of introductions, while climate change may
      decrease the barriers to invader species' spread. We follow an individual-level
      insect- and arachnid-centered perspective to assess how the process of invasion
      is influenced by phenotypic heterogeneity associated with dispersal and stress
      resistance, and their coupling, across the multiple steps of the invasion
      process. We also provide an overview and synthesis on the importance of
      environmental filters during the entire invasion process for the facilitation or
      inhibition of invasive insect population spread. Finally, we highlight important
      research gaps and the relevance and applicability of ongoing natural range
      expansions in the context of climate change to gain essential mechanistic
      insights into insect invasions.

PMID- 29029590
TI  - Nutritional Physiology and Ecology of Honey Bees.
AB  - Honey bees feed on floral nectar and pollen that they store in their colonies as
      honey and bee bread. Social division of labor enables the collection of stores of
      food that are consumed by within-hive bees that convert stored pollen and honey
      into royal jelly. Royal jelly and other glandular secretions are the primary food
      of growing larvae and of the queen but are also fed to other colony members.
      Research clearly shows that bees regulate their intake, like other animals,
      around specific proportions of macronutrients. This form of regulation is done as
      individuals and at the colony level by foragers.

PMID- 29029591
TI  - Application of Microphysiological Systems to Enhance Safety Assessment in Drug
      Discovery.
AB  - Enhancing the early detection of new therapies that are likely to carry a safety
      liability in the context of the intended patient population would provide a major
      advance in drug discovery. Microphysiological systems (MPS) technology offers an
      opportunity to support enhanced preclinical to clinical translation through the
      generation of higher-quality preclinical physiological data. In this review, we
      highlight this technological opportunity by focusing on key target organs
      associated with drug safety and metabolism. By focusing on MPS models that have
      been developed for these organs, alongside other relevant in vitro models, we
      review the current state of the art and the challenges that still need to be
      overcome to ensure application of this technology in enhancing drug discovery.

PMID- 29029592
TI  - Pharmacoepigenetics and Toxicoepigenetics: Novel Mechanistic Insights and
      Therapeutic Opportunities.
AB  - Pharmacological treatment and exposure to xenobiotics can cause substantial
      changes in epigenetic signatures. The majority of these epigenetic changes,
      caused by the compounds in question, occur downstream of transcriptional
      activation mechanisms, whereby the epigenetic alterations can create a
      transcriptional memory and stably modulate cell function. The increasing
      understanding of epigenetic mechanisms and their importance in disease has
      prompted the development of therapeutic interventions that target epigenetic
      modulatory mechanisms, particularly in oncology where inhibitors of epigenetic
      modifying proteins (epidrugs) have been successfully used in treatment, mostly in
      combination with standard-of-care chemotherapy, either provoking direct
      cytotoxicity or inhibiting resistance to anticancer drugs. In addition, emerging
      methods for detecting epigenetically modified DNA in bodily fluids may provide
      information about tumor phenotype or drug treatment success. However, it is
      important to note that many technical pitfalls, such as the nondeconvolution of
      methylcytosine and hydroxymethylcytosine, compromise epigenetic analyses and the
      interpretation of results. In this review, we provide an update on the field,
      with an emphasis on the novel therapeutic opportunities made possible by
      epidrugs.

PMID- 29029593
TI  - Lymphatic Dysfunction, Leukotrienes, and Lymphedema.
AB  - The lymphatic system is essential for the maintenance of tissue fluid
      homeostasis, gastrointestinal lipid absorption, and immune trafficking. Whereas
      lymphatic regeneration occurs physiologically in wound healing and tissue repair,
      pathological lymphangiogenesis has been implicated in a number of chronic
      diseases such as lymphedema, atherosclerosis, and cancer. Insight into the
      regulatory mechanisms of lymphangiogenesis and the manner in which uncontrolled
      inflammation promotes lymphatic dysfunction is urgently needed to guide the
      development of novel therapeutics: These would be designed to reverse lymphatic
      dysfunction, either primary or acquired. Recent investigation has demonstrated
      the mechanistic role of leukotriene B4 (LTB4) in the molecular pathogenesis of
      lymphedema. LTB4, a product of the innate immune response, is a constituent of
      the eicosanoid inflammatory mediator family of molecules that promote both
      physiological and pathological inflammation. Here we provide an overview of
      lymphatic development, the pathophysiology of lymphedema, and the role of
      leukotrienes in lymphedema pathogenesis.

PMID- 29029594
TI  - Chemoreceptors in the Gut.
AB  - The gastrointestinal tract represents the largest interface between the human
      body and the external environment. It must continuously monitor and discriminate
      between nutrients that need to be assimilated and harmful substances that need to
      be expelled. The different cells of the gut epithelium are therefore equipped
      with a subtle chemosensory system that communicates the sensory information to
      several effector systems involved in the regulation of appetite, immune
      responses, and gastrointestinal motility. Disturbances or adaptations in the
      communication of this sensory information may contribute to the development or
      maintenance of disease. This is a new emerging research field in which perception
      of taste can be considered as a novel key player participating in the regulation
      of gut function. Specific diets or agonists that target these chemosensory
      signaling pathways may be considered as new therapeutic targets to tune adequate
      physiological processes in the gut in health and disease.

PMID- 29029595
TI  - 2-Hydroxyoleic acid-inserted liposomes as a multifunctional carrier of anticancer
      drugs.
AB  - Studies have shown that insertion of oleic acid into lipid bilayers can modulate
      the membrane properties of liposomes so as to improve their function as drug
      carriers. Considering that 2-hydroxyoleic acid (2OHOA), a potential antitumor
      agent currently undergoing clinical trials, is a derivative of oleic acid, we
      explored the possibility of developing 2OHOA-inserted liposomes as a
      multifunctional carrier of antitumor drugs in the present study. The insertion of
      2OHOA into lipid bilayers was confirmed by surface charge determination and
      differential scanning calorimetry. 2OHOA insertion greatly decreased the order of
      dimyristoylphosphatidylcholine packing, produced a nanosized (<100 nm)
      dispersion, and improved the colloidal stability of liposomes during storage.
      Moreover, 2OHOA-inserted liposome forms exhibited greater growth inhibitory
      activity against cancer cells compared with free 2OHOA, and the growth-inhibitory
      activity of liposomal 2OHOA was selective for tumor cells. 2OHOA insertion
      greatly increased the liposome-incorporated concentration of hydrophobic model
      drugs, including mitoxantrone, paclitaxel, and all-trans retinoic acid (ATRA).
      The in vitro anticancer activity of ATRA-incorporated/2OHOA-inserted liposomes
      was significantly higher than that of ATRA-incorporated conventional liposomes.
      In a B16-F10 melanoma syngeneic mouse model, the tumor growth rate was
      significantly delayed in mice treated with ATRA-incorporated/2OHOA-inserted
      liposomes compared with that in the control group. Immunohistochemical analyses
      revealed that the enhanced antitumor activity of ATRA-incorporated/2OHOA-inserted
      liposomes was due, at least in part, to increased induction of apoptosis.
      Collectively, our findings indicate that 2OHOA-inserted liposomes exhibit
      multiple advantages as antitumor drug carriers, including the ability to
      simultaneously deliver two anticancer drugs - 2OHOA and incorporated drug - to
      the tumor tissue.

PMID- 29029597
TI  - Identification of novel natural inhibitors of Opisthorchis felineus cytochrome
      P450 using structure-based screening and molecular dynamic simulation.
AB  - Opisthorchis felineus is the etiological agent of opisthorchiasis in humans. O.
      felineus cytochrome P450 (OfCYP450) is an important enzyme in the parasite
      xenobiotic metabolism. To identify the potential anti-opisthorchid compound, we
      conducted a structure-based virtual screening of natural compounds from the ZINC
      database (n = 1,65,869) against the OfCYP450. The ligands were screened against
      OfCYP450 in four sequential docking modes that resulted in 361 ligands having
      better docking score. These compounds were evaluated for Lipinski and ADMET
      prediction, and 10 compounds were found to fit well with re-docking studies.
      After refinement by docking and drug-likeness analyses, four potential inhibitors
      (ZINC2358298, ZINC8790946, ZINC70707116, and ZINC85878789) were identified. These
      ligands with reference compounds (itraconazole and fluconazole) were further
      subjected to molecular dynamics simulation (MDS) and binding energy analyses to
      compare the dynamic structure of protein after ligand binding and the stability
      of the OfCYP450 and bound complexes. The binding energy analyses were also
      calculated. The results suggested that the compounds had a negative binding
      energy with -259.41, -110.09, -188.25, -163.30, -202.10, and -158.79 kJ mol-1 for
      itraconazole, fluconazole, and compounds with IDs ZINC2358298, ZINC8790946,
      ZINC70707116, and ZINC85878789, respectively. These lead compounds displayed
      significant pharmacological and structural properties to be drug candidates. On
      the basis of MDS results and binding energy analyses, we concluded that
      ZINC8790946, ZINC70707116, and ZINC85878789 have excellent potential to inhibit
      OfCYP450.

PMID- 29029596
TI  - Additional Visualization via Smart Glasses Improves Accuracy of Wire Insertion in
      Fracture Surgery.
AB  - BACKGROUND: Smart glasses (SG) are a wearable device consisting of a small
      computer built into a head-mounted monitor (HMM) that can display various kinds
      of information. Lateral side visualization is displayed on the HMM of SG so the
      operator may also see it and the anteroposterior (AP) direction simultaneously.
      The present pilot study aimed to investigate the usefulness of SG in wire
      insertion for bone fracture. METHODS: We marked both the front and lateral sides
      of the shaft of an artificial femur bone. From the tip of the greater trochanter,
      we inserted a 2.4-mm Kirschner wire (K-wire) so that it could be directed toward
      the marks in both planes. Three surgeons enrolled in the study each performed 10
      trials, both with SG (SG arm) and without (direct vision arm). We defined the
      error angle as the angle between the K-wire and the line connecting the marking
      point from the insertion point in both the front and lateral view images. We also
      measured the time it took to insert the K-wire in both arms. RESULTS: The SG had
      a significantly reduced (mean = 3.2 degrees ) error angle ( P = .02) when
      compared to the direct vision group (mean = 4.8 degrees ). However, no
      significant difference was found between direct vision (mean = 17.5 seconds) and
      SG arms (mean = 14.9 seconds) in the insertion time. CONCLUSION: While keeping
      the AP image view in primary focus, simultaneously viewing the lateral side of
      the surgical field using SG helps achieve more accurate wire insertion in
      surgery.

PMID- 29029598
TI  - A method for named entity normalization in biomedical articles: application to
      diseases and plants.
AB  - BACKGROUND: In biomedical articles, a named entity recognition (NER) technique
      that identifies entity names from texts is an important element for extracting
      biological knowledge from articles. After NER is applied to articles, the next
      step is to normalize the identified names into standard concepts (i.e., disease
      names are mapped to the National Library of Medicine's Medical Subject Headings
      disease terms). In biomedical articles, many entity normalization methods rely on
      domain-specific dictionaries for resolving synonyms and abbreviations. However,
      the dictionaries are not comprehensive except for some entities such as genes. In
      recent years, biomedical articles have accumulated rapidly, and neural network
      based algorithms that incorporate a large amount of unlabeled data have shown
      considerable success in several natural language processing problems. RESULTS: In
      this study, we propose an approach for normalizing biological entities, such as
      disease names and plant names, by using word embeddings to represent semantic
      spaces. For diseases, training data from the National Center for Biotechnology
      Information (NCBI) disease corpus and unlabeled data from PubMed abstracts were
      used to construct word representations. For plants, a training corpus that we
      manually constructed and unlabeled PubMed abstracts were used to represent word
      vectors. We showed that the proposed approach performed better than the use of
      only the training corpus or only the unlabeled data and showed that the
      normalization accuracy was improved by using our model even when the dictionaries
      were not comprehensive. We obtained F-scores of 0.808 and 0.690 for normalizing
      the NCBI disease corpus and manually constructed plant corpus, respectively. We
      further evaluated our approach using a data set in the disease normalization task
      of the BioCreative V challenge. When only the disease corpus was used as a
      dictionary, our approach significantly outperformed the best system of the task.
      CONCLUSIONS: The proposed approach shows robust performance for normalizing
      biological entities. The manually constructed plant corpus and the proposed model
      are available at http://gcancer.org/plant and http://gcancer.org/normalization ,
      respectively.

PMID- 29029599
TI  - LiverWiki: a wiki-based database for human liver.
AB  - BACKGROUND: Recent advances in omics technology have produced a large amount of
      liver-related data. A comprehensive and up-to-date source of liver-related data
      is needed to allow biologists to access the latest data. However, current liver
      related data sources each cover only a specific part of the liver. It is
      difficult for them to keep pace with the rapid increase of liver-related data
      available at those data resources. Integrating diverse liver-related data is a
      critical yet formidable challenge, as it requires sustained human effort.
      RESULTS: We present LiverWiki, a first wiki-based database that integrates liver
      related genes, homolog genes, gene expressions in microarray datasets and RNA-Seq
      datasets, proteins, protein interactions, post-translational modifications,
      associated pathways, diseases, metabolites identified in the metabolomics
      datasets, and literatures into an easily accessible and searchable resource for
      community-driven sharing. LiverWiki houses information in a total of 141,897
      content pages, including 19,787 liver-related gene pages, 17,077 homolog gene
      pages, 50,251 liver-related protein pages, 36,122 gene expression pages, 2067
      metabolites identified in the metabolomics datasets, 16,366 disease-related
      molecules, and 227 liver disease pages. Other than assisting users in searching,
      browsing, reviewing, refining the contents on LiverWiki, the most important
      contribution of LiverWiki is to allow the community to create and update
      biological data of liver in visible and editable tables. This integrates newly
      produced data with existing knowledge. Implemented in mediawiki, LiverWiki
      provides powerful extensions to support community contributions. CONCLUSIONS: The
      main goal of LiverWiki is to provide the research community with comprehensive
      liver-related data, as well as to allow the research community to share their
      liver-related data flexibly and efficiently. It also enables rapid sharing new
      discoveries by allowing the discoveries to be integrated and shared immediately,
      rather than relying on expert curators. The database is available online at
      http://liverwiki.hupo.org.cn /.

PMID- 29029600
TI  - Clinical features and CKD-related quality of life in patients with CKD G3a and
      CKD G3b in China: results from the Chinese Cohort Study of Chronic Kidney Disease
      (C-STRIDE).
AB  - BACKGROUND: This study aimed to compare clinical features and health-related
      quality of life (HRQoL) in the Chinese chronic kidney disease (CKD) 3 population
      and determined the necessity of the subdivision of CKD3 in Chinese patients with
      CKD. METHODS: Participants with stage 3 CKD (18-74 years of age) were recruited
      at 39 clinical centers located at 28 cities in 22 provinces of China. The
      sociodemographic status, medical history, anthropometric measurements, and
      lifestyle behaviors were documented at entry, and blood and urine samples were
      collected. The estimated glomerular filtration rate was calculated using the CKD
      EPI creatinine equation. The HRQoL was evaluated using the kidney disease quality
      of-life instrument. A linear regression model was used to estimate the
      association between HRQoL and CKD stages (G3b vs G3a). RESULTS: The levels of
      intact parathyroid hormone, systolic blood pressure, uric acid, and high-density
      lipoprotein cholesterol were statistically significantly higher, whereas the
      levels of serum bicarbonate and hemoglobin were statistically significantly lower
      in the G3b group compared with the G3a group. Compared with CKD G3a group, the
      proportions of subjects with hyperuricemia and anemia were significantly higher
      in CKD G3b group (61.4% vs. 52.0% and 26.4% vs. 17.9%, respectively, P< 0.01).
      The HRQoL scores in "physical functioning (PCS)", "symptoms and problems",
      "effects of the kidney disease" and "burden of the kidney disease" were
      statistically significantly lower in the CKD G3b group compared with the CKD G3a
      group (90.88 +/- 11.05 vs. 89.30 +/- 11.52, 88.29 +/- 11.94 vs. 86.49 +/- 13.45,
      55.86 +/- 26.40 vs. 52.10 +/- 27.64, 46.56 +/- 8.16 vs. 44.51 +/- 9.22,
      respectively, P< 0.01). Further, CKD G3b was associated with a lower score of
      physical functioning compared with G3a (regression coefficient =-1.12 [95%CI: 
      2.23, -0.16]). CONCLUSIONS: The preliminary results of this study suggested that
      modest differences existed in many important clinical features and KDQoL between
      patients with G3a and G3b CKD in a Chinese population. Also, a significant
      association between CKD3 subdivision of the disease and PCS was detected.
      Although further work is needed, we can speculate based on these results the CKD3
      subdivision may be clinically meaningful for Chinese patients with CKD.

PMID- 29029601
TI  - Prevalence and risk factors for myopia in older adult east Chinese population.
AB  - BACKGROUND: To determine the prevalence and associated factors for myopia and
      high myopia among older population in a rural community in Eastern China.
      METHODS: A community-based, cross-sectional survey was conducted in the Weitang
      town located in Suzhou, an urban metropolis in East China. A total of 5613
      Chinese residents aged 60 years and older were invited to complete a
      questionnaire and participated in a detailed eye examination,including
      measurements of visual acuity and refractive error using autorefraction and
      subjective refraction. Myopia and high myopia was defined as SE < -0.5 diopters
      (D) and < -5.0 D, respectively. RESULTS: Among the 5613 participating
      individuals, 4795 (85.4%) complete refraction data of phakic right eye was
      included for analysis. The age-adjusted prevalence was 21.1% (95% confidence
      interval [CI], 19.9-22.2) for myopia and 2.5% (95% CI, 2.1-2.9) for high myopia.
      The prevalence of myopia tended to increase significantly with age(p < 0.001),and
      women had a higher rate of myopia than men (p < 0.001). According to multivariate
      logistic regression analysis, adults who were older (odds ration[OR]:1.05; 95%
      CI:1.04-1.07), spent more time for sleeping at night (OR:1.12;95% CI: 1.06
      1.18),or had cataract (OR:1.60;95% CI:1.36-1.88) and family history of myopia
      (OR:1.47;95% CI:1.23-1.77), are more susceptible to myopia (p < 0.001). People
      who had older age, family history, cataract and specially longer night-time sleep
      duration, would have a higher risk of myopia. CONCLUSION: Myopia and high myopia
      among rural old adult population in Eastern China presents common. The current
      literature unanticipated suggests that there was a positive significant
      association between prevalence of myopia and night-time sleep duration among
      adult. Our data provide some evidence of this relationship and highlight the need
      for larger studies to further investigate this relationship longitudinally and
      explore mechanism therein.

PMID- 29029602
TI  - eRP arrangement: a strategy for assembled genomic contig rearrangement based on
      replication profiling in bacteria.
AB  - BACKGROUND: The reduced cost of sequencing has made de novo sequencing and the
      assembly of draft microbial genomes feasible in any ordinary biology lab.
      However, the process of finishing and completing the genome remains labor
      intensive and computationally challenging in some cases, such as in the study of
      complete genome sequences, genomic rearrangements, long-range syntenic
      relationships, and structural variations. METHODS: Here, we show a contig
      reordering strategy based on experimental replication profiling (eRP) to
      recapitulate the bacterial genome structure within draft genomes. During the
      exponential growth phase, the majority of bacteria show a global genomic copy
      number gradient that is enriched near the replication origin and gradually
      declines toward the terminus. Therefore, if genome sequencing is performed with
      appropriate timing, the short-read coverage reflects this copy number gradient,
      providing information about the contig positions relative to the replication
      origin and terminus. RESULTS: We therefore investigated the appropriate timing
      for genomic DNA sampling and developed an algorithm for the reordering of the
      contigs based on eRP. As a result, this strategy successfully recapitulates the
      genomic structure of various structural mutants with draft genome sequencing.
      CONCLUSIONS: Our strategy was successful for contig rearrangement with
      intracellular DNA replication behavior mechanisms and can be applied to almost
      all bacteria because the DNA replication system is highly conserved. Therefore,
      eRP makes it possible to understand genomic structural information and long-range
      syntenic relationships using a draft genome that is based on short reads.

PMID- 29029604
TI  - Trauma burden in Tanzania: a one-day survey of all district and regional public
      hospitals.
AB  - BACKGROUND: Trauma contributes significantly to the burden of disease and
      mortality throughout the world, but particularly in developing countries. In
      Tanzania, there is an enormous research gap on trauma; the limited data available
      reflects realities in cities and areas with moderately- to highly-resourced
      treatment centers. Our aim was to provide a description of the injury
      epidemiology across all of Tanzania. Our data will serve as a basis for future
      larger studies. METHODS: This is a subgroup analysis of a cross-sectional,
      prospective study of the clinical epidemiology of patients presenting at all
      public district and regional hospitals in Tanzania. The study was conducted
      between May 2012 and December 2012. A team of emergency doctors used a purpose
      designed data collection sheet to gather the demographic and clinical information
      of all patients presenting during the day-site visit to each hospital.
      Descriptive statistics, including means, standard deviations, medians, and ranges
      are reported. RESULTS: A total of 5227 patients were seen in 24-h period in 105
      (100% response rate) district (or designated district) and regional hospitals in
      mainland Tanzania. Of these patients, 508 (9.7%) presented with trauma-related
      complaints. Among patients with trauma-related complaints, 286 (56.3%) were male,
      and the overall median age of 30 (interquartile range of 22-35) years. Road
      traffic crash was the most common mechanism of injury, accounting for 227 (44.7%)
      complaints. Open wounds and bone fractures were the two most frequent diagnoses,
      with a combined 300 (59%) cases. Most of the patients - 325 (64%) - were
      discharged, 11 (2.2%) went to operating theatres and 4 (0.8%) of patients died
      while receiving care at the acute intake areas. CONCLUSIONS: Trauma-related
      complaints constitute a substantial burden among patients seeking care in acute
      intake areas of hospitals across Tanzania. There is a need to develop, implement
      and study systems that can support the improvement of trauma care and optimize
      outcomes of trauma patients.

PMID- 29029603
TI  - The pathophysiological role of mitochondrial oxidative stress in lung diseases.
AB  - Mitochondria are critically involved in reactive oxygen species (ROS)-dependent
      lung diseases, such as lung fibrosis, asbestos, chronic airway diseases and lung
      cancer. Mitochondrial DNA (mtDNA) encodes mitochondrial proteins and is more
      sensitive to oxidants than nuclear DNA. Damage to mtDNA causes mitochondrial
      dysfunction, including electron transport chain impairment and mitochondrial
      membrane potential loss. Furthermore, damaged mtDNA also acts as a damage
      associated molecular pattern (DAMP) that drives inflammatory and immune
      responses. In this review, crosstalk among alveolar epithelial cells, alveolar
      macrophages and mitochondria is examined. ROS-related transcription factors and
      downstream cell signaling pathways are also discussed. We conclude that targeting
      oxidative stress with antioxidant agents, such as thiol molecules, polyphenols
      and superoxide dismutase (SOD), and promoting mitochondrial biogenesis should be
      considered as novel strategies for treating lung diseases that currently have no
      effective treatment options.

PMID- 29029605
TI  - Monitoring multiple myeloma by idiotype-specific peptide binders of tumor-derived
      exosomes.
AB  - Tumor-derived exosomes (TDEs) play a pivotal role in tumor establishment and
      progression, and are emerging biomarkers for tumor diagnosis in personalized
      medicine. To date, there is a lack of efficient technology platforms for exosome
      isolation and characterization. Multiple myeloma (MM) is an incurable B-cell
      malignancy due to the rapid development of drug-resistance. MM-released exosomes
      express the immunoglobulin B-cell receptor (Ig-BCR) of the tumor B-cells, which
      can be targeted by Idiotype-binding peptides (Id-peptides). In this study, we
      analyzed the production of MM-released exosomes in the murine 5T33MM multiple
      myeloma model as biomarkers of tumor growth. To this end, we selected Id-peptides
      by screening a phage display library using as bait the Ig-BCR expressed by 5T33MM
      cells. By FACS, the FITC-conjugated Id-peptides detected the MM-released exosomes
      in the serum of 5T33MM-engrafted mice, levels of which are correlated with tumor
      progression at an earlier time point compared to serum paraprotein. These results
      indicate that Id-peptide-based recognition of MM-released exosomes may represent
      a very sensitive diagnostic approach for clinical evaluation of disease
      progression.

PMID- 29029606
TI  - Patient-centered professional practice models for managing low back pain in older
      adults: a pilot randomized controlled trial.
AB  - BACKGROUND: Low back pain is a debilitating condition for older adults, who may
      seek healthcare from multiple providers. Few studies have evaluated impacts of
      different healthcare delivery models on back pain outcomes in this population.
      The purpose of this study was to compare clinical outcomes of older adults
      receiving back pain treatment under 3 professional practice models that included
      primary medical care with or without chiropractic care. METHODS: We conducted a
      pilot randomized controlled trial with 131 community-dwelling, ambulatory older
      adults with subacute or chronic low back pain. Participants were randomly
      allocated to 12 weeks of individualized primary medical care (Medical Care),
      concurrent medical and chiropractic care (Dual Care), or medical and chiropractic
      care with enhanced interprofessional collaboration (Shared Care). Primary
      outcomes were low back pain intensity rated on the numerical rating scale and
      back-related disability measured with the Roland-Morris Disability Questionnaire.
      Secondary outcomes included clinical measures, adverse events, and patient
      satisfaction. Statistical analyses included mixed-effects regression models and
      general estimating equations. RESULTS: At 12 weeks, participants in all three
      treatment groups reported improvements in mean average low back pain intensity
      [Shared Care: 1.8; 95% confidence interval (CI) 1.0 to 2.6; Dual Care: 3.0; 95%
      CI 2.3 to 3.8; Medical Care: 2.3; 95% CI 1.5 to 3.2)] and back-related disability
      (Shared Care: 2.8; 95% CI 1.6 to 4.0; Dual Care: 2.5; 95% CI 1.3 to 3.7; Medical
      Care: 1.5; 95% CI 0.2 to 2.8). No statistically significant differences were
      noted between the three groups on the primary measures. Participants in both
      models that included chiropractic reported significantly better perceived low
      back pain improvement, overall health and quality of life, and greater
      satisfaction with healthcare services than patients who received medical care
      alone. CONCLUSIONS: Professional practice models that included primary care and
      chiropractic care led to modest improvements in low back pain intensity and
      disability for older adults, with chiropractic-inclusive models resulting in
      better perceived improvement and patient satisfaction over the primary care model
      alone. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01312233 , 4 March 2011.

PMID- 29029607
TI  - miRNAs involved in the development and differentiation of fertile and sterile
      flowers in Viburnum macrocephalum f. keteleeri.
AB  - BACKGROUND: Sterile and fertile flowers are important evolutionary developmental
      phenotypes in angiosperm flowers. The development of floral organs, critical in
      angiosperm reproduction, is regulated by microRNAs (miRNAs). However, the
      mechanisms underpinning the miRNA regulation of the differentiation and
      development of sterile and fertile flowers remain unclear. RESULTS: Here, based
      on investigations of the morphological differences between fertile and sterile
      flowers, we used high-throughput sequencing to characterize the miRNAs in the
      differentiated floral organs of Viburnum macrocephalum f. keteleeri. We
      identified 49 known miRNAs and 67 novel miRNAs by small RNA (sRNA) sequencing and
      bioinformatics analysis, and 17 of these known and novel miRNA precursors were
      validated by polymerase chain reaction (PCR) and Sanger sequencing. Furthermore,
      by comparing the sequencing results of two sRNA libraries, we found that 30 known
      and 39 novel miRNA sequences were differentially expressed, and 35 were
      upregulated and 34 downregulated in sterile compared with fertile flowers.
      Combined with their predicted targets, the potential roles of miRNAs in V.
      macrocephalum f. keteleeri flowers include involvement in floral organogenesis,
      cell proliferation, hormonal pathways, and stress responses. miRNA precursors and
      targets were further validated by quantitative real-time PCR (qRT-PCR).
      Specifically, miR156a-5p, miR156g, and miR156j expression levels were
      significantly higher in fertile flowers than in sterile flowers, while SPL genes
      displayed the opposite expression pattern. Considering that the targets of miR156
      are predicted to be SPL genes, we propose that miR156 may be involved in the
      regulation of stamen development in V. macrocephalum f. keteleeri. CONCLUSIONS:
      We identified miRNAs differentially expressed between fertile and sterile flowers
      in V. macrocephalum f. keteleeri and provided new insights into the important
      regulatory roles of miRNAs in the differentiation and development of fertile and
      sterile flowers.

PMID- 29029609
TI  - Modelling the implications of stopping vector control for malaria control and
      elimination.
AB  - BACKGROUND: Increasing coverage of malaria vector control interventions globally
      has led to significant reductions in disease burden. However due to its high
      recurrent cost, there is a need to determine if and when vector control can be
      safely scaled back after transmission has been reduced. METHODS AND FINDINGS: A
      mathematical model of Plasmodium falciparum malaria epidemiology was simulated to
      determine the impact of scaling back vector control on transmission and disease.
      A regression analysis of simulation results was conducted to derive predicted
      probabilities of resurgence, severity of resurgence and time to resurgence under
      various settings. Results indicate that, in the absence of secular changes in
      transmission, there are few scenarios where vector control can be removed without
      high expectation of resurgence. These, potentially safe, scenarios are
      characterized by low historic entomological inoculation rates, successful vector
      control programmes that achieve elimination or near elimination, and effective
      surveillance systems with high coverage and effective treatment of malaria cases.
      CONCLUSIONS: Programmes and funding agencies considering scaling back or
      withdrawing vector control from previously malaria endemic areas need to first
      carefully consider current receptivity and other available interventions in a
      risk assessment. Surveillance for resurgence needs to be continuously conducted
      over a long period of time in order to ensure a rapid response should vector
      control be withdrawn.

PMID- 29029608
TI  - Association of trace metal elements with lipid profiles in type 2 diabetes
      mellitus patients: a cross sectional study.
AB  - BACKGROUND: It is well known that dyslipidemia and chronic hyperglycemia increase
      the onset of diabetes and diabetic complication. The aim of this study is to see
      the association of trace metals elements and lipid profile among type 2 diabetes
      mellitus patients. METHODS: The study was conducted on 214 type 2 diabetic
      patients at Jimma University Specialized Hospital, Jimma, Ethiopia. All the
      eligible study participants responded to the structured interviewer administered
      questionnaire and fasting venous blood was drawn for biochemical analysis. Trace
      metal elements (zinc(Zn+2), magnesium(Mg+2), chromium(Cr+3), calcium(Ca+2),
      phosphorus(Po4-3), manganese(Mn+2), copper(Cu+2), and iron(Fe+3)) and lipid
      profiles (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C),
      high-density lipoprotein (HDL-C), and triglycerides (TG)) were measured by atomic
      absorption spectrophotometry and enzymatic determination method respectively.
      Data were analyzed by SPSS version 24 software for windows. Bonferroni correction
      for multiple statistical comparisons was used and a p-value less than 0.01 were
      accepted as a level of significance. RESULT: The mean age of study participants
      was 42.95(+/-12.6) with an average of 5.83(+/-3.1) years being diagnosed with
      diabetes mellitus. The BMI of female (27.1(+/-4.9)) was significantly higher than
      male (25.21(+/-4.2)). BMI shows positive and significant (p < 0.01) association
      with lipid profiles (TC, LDL-C, and TG) among type 2 diabetic patients in the
      liner regression model. In addition, WH-R was positively associated with TG. In
      Pearson partial correlation adjusted for sex and age, Za+2 shown to have
      statistically significant and negative correlations with TC, LDL-C and with TG.
      Mg+2 and Cr+2 negatively and significantly correlated with the lipid profile TC
      and LDL-C. Ca+2 negatively correlated with TC and TG. Po-34 positively correlated
      with HDL-C; iron negatively correlated with TC. However, in the liner regression
      model, only calcium positively and significantly (Beta = -0.21, p < 0.01)
      associated with TG. CONCLUSION: In the current study, a negative correlation was
      observed between trace metal elements (Zn+2, Mg+2, Cr+3, Ca+2 and Fe+3) and lipid
      profile (TC, LDL-C and TG) among type 2 diabetes mellitus patients. In addition,
      Ca+2 observed to be associated with TG. Future studies are highly advised to
      uncover the bidirectional association between trace metal element and
      dyslipidemia in diabetic patients.

PMID- 29029610
TI  - Infection by and genotype characteristics of Enterocytozoon bieneusi in HIV/AIDS
      patients from Guangxi Zhuang autonomous region, China.
AB  - BACKGROUND: Enterocytozoon bieneusi has been increasingly reported to infect
      humans and various mammals. Microsporidia cause diarrhea in HIV-infected patients
      worldwide. PCR amplification and sequencing based on the internal transcribed
      spacer region have been used to describe the genotypes of E. bieneusi and
      transmission of microsporidiosis. METHODS: In this study, we examined E. bieneusi
      infection and genotypes in HIV-positive patients in Guangxi, China. Stool
      specimens were collected from 285 HIV-positive patients and 303 HIV-negative
      individuals. E. bieneusi genotypes were characterized using nested PCR and
      sequencing. RESULTS: Thirty-three (11.58%) HIV-positive patients were infected
      with microsporidia, and no infection was found in the 303 healthy controls. Three
      new genotypes were identified and named as GX25, GX456, and GX458; four known
      genotypes, PigEBITS7, Type IV/K, D, and Ebpc, were also identified. Our data
      showed that the positive rate for microsporidia was significantly higher in the
      rural patients than in the other occupation groups. In addition, the positive
      rate for microsporidia was significantly higher in the patients who drink
      unboiled water than in those with other drinking water sources. CONCLUSIONS: Our
      results will provide baseline data for preventing and controlling E. bieneusi
      infection in HIV/AIDS patients. Further studies are required to clarify the
      epidemiology and potential sources of microsporidia. Our study showed that
      microsporidium infection occurs in the HIV/AIDS patients in Guangxi, China.

PMID- 29029612
TI  - The relative efficiency of Iranian's rural traffic police: a three-stage DEA
      model.
AB  - BACKGROUND: Road traffic Injuries (RTIs) as a health problem imposes governments
      to implement different interventions. Target achievement in this issue required
      effective and efficient measures. Efficiency evaluation of traffic police as one
      of the responsible administrators is necessary for resource management.
      Therefore, this study conducted to measure Iran's rural traffic police
      efficiency. METHODS: This was an ecological study. To obtain pure efficiency
      score, three-stage DEA model was conducted with seven inputs and three output
      variables. At the first stage, crude efficiency score was measured with BCC-O
      model. Next, to extract the effects of socioeconomic, demographic, traffic count
      and road infrastructure as the environmental variables and statistical noise, the
      Stochastic Frontier Analysis (SFA) model was applied and the output values were
      modified according to similar environment and statistical noise conditions. Then,
      the pure efficiency score was measured using modified outputs and BCC-O model.
      RESULTS: In total, the efficiency score of 198 police stations from 24 provinces
      of 31 provinces were measured. The annual means (standard deviation) of damage,
      injury and fatal accidents were 247.7 (258.4), 184.9 (176.9), and 28.7 (19.5),
      respectively. Input averages were 5.9 (3.0) patrol teams, 0.5% (0.2) manpower
      proportions, 7.5 (2.9) patrol cars, 0.5 (1.3) motorcycles, 77,279.1 (46,794.7)
      penalties, 90.9 (2.8) cultural and educational activity score, 0.7 (2.4) speed
      cameras. The SFA model showed non-significant differences between police station
      performances and the most differences attributed to the environmental and random
      error. One-way main road, by road, traffic count and the number of household
      owning motorcycle had significant positive relations with inefficiency score. The
      length of freeway/highway and literacy rate variables had negative relations,
      significantly. Pure efficiency score was with mean of 0.95 and SD of 0.09.
      CONCLUSIONS: Iran's traffic police has potential opportunity to reduce RTIs.
      Adjusting police performance with environmental conditions is necessary.
      Capability of DEA method in setting quantitative targets for every station
      induces motivation for managers to reduce RTIs. Repetition of this study is
      recommended, annually.

PMID- 29029611
TI  - Identification of 15 candidate structured noncoding RNA motifs in fungi by
      comparative genomics.
AB  - BACKGROUND: With the development of rapid and inexpensive DNA sequencing, the
      genome sequences of more than 100 fungal species have been made available. This
      dataset provides an excellent resource for comparative genomics analyses, which
      can be used to discover genetic elements, including noncoding RNAs (ncRNAs).
      Bioinformatics tools similar to those used to uncover novel ncRNAs in bacteria,
      likewise, should be useful for searching fungal genomic sequences, and the
      relative ease of genetic experiments with some model fungal species could
      facilitate experimental validation studies. RESULTS: We have adapted a
      bioinformatics pipeline for discovering bacterial ncRNAs to systematically
      analyze many fungal genomes. This comparative genomics pipeline integrates
      information on conserved RNA sequence and structural features with alternative
      splicing information to reveal fungal RNA motifs that are candidate regulatory
      domains, or that might have other possible functions. A total of 15 prominent
      classes of structured ncRNA candidates were identified, including variant HDV
      self-cleaving ribozyme representatives, atypical snoRNA candidates, and possible
      structured antisense RNA motifs. Candidate regulatory motifs were also found
      associated with genes for ribosomal proteins, S-adenosylmethionine decarboxylase
      (SDC), amidase, and HexA protein involved in Woronin body formation. We
      experimentally confirm that the variant HDV ribozymes undergo rapid self
      cleavage, and we demonstrate that the SDC RNA motif reduces the expression of SAM
      decarboxylase by translational repression. Furthermore, we provide evidence that
      several other motifs discovered in this study are likely to be functional ncRNA
      elements. CONCLUSIONS: Systematic screening of fungal genomes using a
      computational discovery pipeline has revealed the existence of a variety of novel
      structured ncRNAs. Genome contexts and similarities to known ncRNA motifs provide
      strong evidence for the biological and biochemical functions of some newly found
      ncRNA motifs. Although initial examinations of several motifs provide evidence
      for their likely functions, other motifs will require more in-depth analysis to
      reveal their functions.

PMID- 29029613
TI  - Right precordial-directed electrocardiographical markers identify arrhythmogenic
      right ventricular cardiomyopathy in the absence of conventional depolarization or
      repolarization abnormalities.
AB  - BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)
      carries a risk of sudden death. We aimed to assess whether vectorcardiographic
      (VCG) parameters directed toward the right heart and a measured angle of the S
      wave would help differentiate ARVD/C with otherwise normal electrocardiograms
      from controls. METHODS: Task Force 2010 definite ARVD/C criteria were met for all
      patients. Those who did not fulfill Task Force depolarization or repolarization
      criteria (-ECG) were compared with age and gender-matched control subjects.
      Electrocardiogram measures of a 3-dimentional spatial QRS-T angle, a right
      precordial-directed orthogonal QRS-T (RPD) angle, a root mean square of the right
      sided depolarizing forces (RtRMS-QRS), QRS duration (QRSd) and the corrected QT
      interval (QTc), and a measured angle including the upslope and downslope of the S
      wave (S-wave angle) were assessed. RESULTS: Definite ARVD/C was present in 155
      patients by 2010 Task Force criteria (41.7 +/- 17.6 years, 65.2% male). -ECG
      ARVD/C patients (66 patients) were compared to 66 control patients (41.7 +/- 17.6
      years, 65.2% male). All parameters tested except the QRSd and QTc significantly
      differentiated -ECG ARVD/C from control patients (p < 0.004 to p < 0.001). The
      RPD angle and RtRMS-QRS best differentiated the groups. Combined, the 2 novel
      criteria gave 81.8% sensitivity, 90.9% specificity and odds ratio of 45.0 (95%
      confidence interval 15.8 to 128.2). CONCLUSION: ARVD/C disease process may lead
      to development of subtle ECG abnormalities that can be distinguishable using
      right-sided VCG or measured angle markers better than the spatial QRS-T angle,
      the QRSd or QTc, in the absence of Taskforce ECG criteria.

PMID- 29029614
TI  - Field assessment of a novel spatial repellent for malaria control: a feasibility
      and acceptability study in Mondulkiri, Cambodia.
AB  - BACKGROUND: Large-scale use of insecticide-treated nets and indoor residual
      spraying have contributed to a significant decrease in malaria transmission
      worldwide. Further reduction and progress towards elimination, however, require
      complementary control measures which can address the remaining gaps in protection
      from mosquito bites. Following the development of novel pyrethroids with high
      knockdown effects on malaria vectors, programmatic use of spatial repellents has
      been suggested as one potential strategy to fill the gaps. This report explores
      social and contextual factors that may influence the relevance, uptake and
      sustainable use of a spatial repellent in two remote villages in Mondulkiri
      province, Cambodia, with endemic malaria transmission. The repellent consisted of
      polyethylene emanators, held in an open plastic frame and impregnated with 10%
      metofluthrin. RESULTS: In a baseline survey, 90.9% of households in Ou Chra (n =
      30/33) and 96.6% in Pu Cha (n = 57/59) were interviewed. Behavioural data were
      collected for all household occupants (n = 448). In both villages, there were
      times and places in which people remained exposed to mosquito bites. Prior to the
      installation of the repellent, 50.6 and 59.5% of respondents noted that bites
      occurred "very often" inside the house and in the outdoor area surrounding the
      house, respectively. Indoor biting was reported to occur more frequently in the
      evening, followed by at night, while outdoor biting occurred more frequently in
      the early morning. In a follow-up survey, spatial repellents were well received
      in both villages, although 63.2% of respondents would not replace bed nets with
      repellents. Most participants (96.6%) were willing to use the product again; the
      mean willingness to pay was US$ 0.3 per unit. A preference for local procurement
      methods emerged. CONCLUSION: Widespread use of spatial repellents would not fill
      all protective gaps, but, if their entomological efficacy can be ascertained,
      outdoor application has the potential to enhance vector control strategies in
      Cambodia. Successful implementation would require subsidisation and integration
      with the existing national malaria control strategy. It is hoped that this study,
      while contributing to a better understanding of the social contexts of residual
      malaria transmission, will generate further interest in the evaluation of spatial
      repellents for malaria control.

PMID- 29029615
TI  - Fenofibrate decreases the bone quality by down regulating Runx2 in high-fat-diet
      induced Type 2 diabetes mellitus mouse model.
AB  - BACKGROUND: This study is to investigate the effect of fenofibrate on the bone
      quality of Type 2 diabetes mellitus (T2DM) mouse model. METHODS: T2DM mouse model
      was induced by high-fat-diet, and the mice were treated with fenofibrate (100
      mg/kg) (DIO-FENO) or PBS (DIO-PBS) for 4 weeks. The bone microstructure and
      biomechanical properties of femora were analyzed by micro-CT and 3-Point bending
      test. The protein expression was detected by immunohistochemical staining and
      Western blot. The cell apoptosis was evaluated by TUNEL staining. The Bcl2,
      caspase 3, and osteoblast marker genes were detected by RT-qPCR. RESULTS: The
      biomechanical properties of bones from DIO-FENO group were significantly lower
      than those in the control and DIO-PBS groups. Besides, the trabecular number was
      lower than those of the other groups, though the cortical porosity was decreased
      compared with that of DIO-PBS group because of the increase of apoptotic cells.
      The expression of osteocalcin and collagen I were decreased after treatment with
      fenofibrate in T2DM mice. Moreover, the cell viability was decreased after
      treated with different concentrations of fenofibrate, and the expression of Runx2
      decreased after treated with high dose of fenofibrate. CONCLUSION: Fenofibrate
      decreases the bone quality of T2DM mice through decreasing the expression of
      collagen I and osteocalcin, which may be resulted from the down regulation of
      Runx2 expression.

PMID- 29029616
TI  - Short term effectiveness and experiences of a peer guided web-based self
      management intervention for young adults with juvenile idiopathic arthritis.
AB  - BACKGROUND: A web-based self-management intervention guided by peer-trainers was
      developed to support young adults' self-management in coping with Juvenile
      Idiopathic Arthritis (JIA). To investigate its effectiveness, a randomized
      controlled trial (RCT) was conducted. In addition, the content of the chat and
      participants' goals were studied to identify underlying processes. METHODS: An
      RCT with a six-month follow up period was conducted among 72 young adults with
      JIA, aged between 16 and 25 years old, randomly assigned to the intervention or
      to the usual care control group. After 24 weeks, in both groups 24 participants
      completed all measurements. Intentions to treat analyses were carried out by
      means of linear mixed models for longitudinal measurements. With self-efficacy as
      primary outcome, self-management, disease activity, quality of life, absenteeism
      of school/work, health care medication use and adherence to the intervention were
      studied. The participants' goals, personal achievements, interactions on the
      chat, and their appreciation of the intervention were analyzed using thematic
      analyses. RESULTS: No significant differences were found on self-efficacy,
      quality of life, and self-management between the participants of the control
      group and the intervention group. In the intervention group, modeling and sharing
      experiences were the most recognized themes. Fifty-five goals were formulated and
      divided into the following categories: improvement and maintaining balance,
      setting and recognizing boundaries, communicating and coping with
      incomprehension. Adherence, appreciation of the own learning experience, and
      personal achievements were rated positively. CONCLUSION: The web-based
      intervention did not lead to an improvement of self-efficacy. However, additional
      qualitative analyses showed that the intervention was appreciated and valuable
      for the participants. More research is needed on how to measure the added value
      of this intervention compared to the usual care. TRIAL REGISTRATION: Trial
      registration number NTR4679 .

PMID- 29029617
TI  - Association of red cell distribution width with all-cause and cardiovascular
      specific mortality in African American and white adults: a prospective cohort
      study.
AB  - BACKGROUND: While the mortality rate is declining in the United States, the life
      expectancy gap among different population groups suggests a need to identify
      biomarkers to improve early identification of individuals at risk. Red cell
      distribution width (RDW), a measure of anisocytosis, is an emerging biomarker of
      chronic disease morbidity and mortality, particularly in the elderly. However,
      little is known about its association with mortality risk in younger adults. The
      objectives of this study were to investigate the association between RDW and
      overall and cause-specific mortality risk, and to identify novel determinants of
      RDW level. METHODS: We used prospectively collected data from the Healthy Aging
      in Neighborhoods of Diversity across the Life Span study conducted in Baltimore,
      Maryland. At baseline (2004-2009), the study recruited 3720 African American and
      white men and women aged 30-64 years. Participants provided peripheral venous
      blood for RDW measurement as part of complete blood count, and genotyping.
      Mortality status was ascertained using the National Death Index database through
      December 31, 2013. Multivariable adjusted Cox proportional hazards regression
      models were fitted to assess mortality risk, and multiple linear regression
      models to identify determinants of RDW level. RESULTS: Participants' mean age was
      48.1 (9.2) years. Of 2726 participants included in the present analyses, 57% were
      African Americans, and 56% were women. After 18,424 person-years of follow-up
      time, there were 226 deaths, and the leading cause of death were cardiovascular
      diseases (31.9%). Participants in the highest quartile of RDW had a 1.73-fold
      increased all-cause mortality risk (highest quartile vs. lowest quartile,
      multivariable adjusted hazard ratio = 1.73, 95% confidence interval: 1.10-2.74, p
      trend = 0.006). This effect was significantly modified by body mass index (p
      interaction = 0.004). Similar risk was observed for cardiovascular disease
      specific mortality. Independent of body mass index, waist-hip ratio and illicit
      drug use were significantly associated with RDW. CONCLUSIONS: Elevated RDW was
      associated with a substantial risk of all-cause and cardiovascular disease
      specific mortalities that was modified by body mass index. Central obesity and
      illicit drug use influence RDW level. In vulnerable populations at-risk for
      health disparities, RDW could provide a useful and inexpensive biomarker of
      mortality.

PMID- 29029618
TI  - Balneotherapeutic effects of high mineral spring water on the atopic dermatitis
      like inflammation in hairless mice via immunomodulation and redox balance.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing allergic inflammatory
      skin disease that currently affects millions of children and adults worldwide.
      Drugs used to treat these inflammatory diseases include anti-histamines,
      corticosteroids and calcineurin inhibitors but these drugs have their limitations
      such as adverse effects with their long-term usage. Thus, researcher's interest
      in several alternative and complementary therapies are continually growing and
      balneotherapy is one of these approaches. Therefore, we investigate the bathing
      effect of high concentration mineral spring water (HMW) on redox balance and
      immune modulation in 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis
      like inflammation in hairless mice. METHODS: We induced AD-like inflammation by
      application of DNCB on the dorsal skin of female skh-1 hairless mice. The mice
      were treated with 100% pure HMW (PHMW) and 10% diluted HMW (DHMW) through bathing
      once a day for 4 weeks. Tacrolimus ointment (0.1%) was used as positive control
      (PC) and only DNCB treatment as negative control (NeC) group. The severity of
      skin lesion inflammation was assessed through clinical scoring and observing
      scratching behavior. Levels of immunoglobulin E (IgE) and inflammatory cytokines
      in serum were detected by ELISA and multiplex bead array system, and the levels
      of oxidative stress-related biomarkers and antioxidant enzyme were also measured.
      RESULTS: We found that HMW significantly decreased the scratching behavior in
      PHMW and DHMW groups at the 2nd week and in PHMW group at 4th week compared to
      NeC group. Likewise, serum IgE level was significantly decreased in DHMW group as
      compared to NeC group. In line, the level of inflammatory cytokines in serum such
      as interleukin (IL)-1beta, IL-13 and tumor necrosis factor-alpha were
      significantly inhibited in PHMW and DHMW groups compared to NeC group. In
      parallel, total reactive oxygen species (ROS) of serum level was significantly
      decreased in PHMW treatment groups compared to NeC group. Consistently, serum
      malondialdehyde (MDA) level in PHMW group was lower than in NeC group. By
      contrast, glutathione peroxidase (GPx) activity was significantly enhanced in
      PHMW than NeC. CONCLUSION: Collectively, our study indicates a balneotherapeutic
      effect of HMW on DNCB-induced AD like inflammation in hairless mice via
      immunomodulation and redox balance.

PMID- 29029619
TI  - Malaria prevalence, prevention and treatment seeking practices among nomadic
      pastoralists in northern Senegal.
AB  - BACKGROUND: Malaria transmission in Senegal is highly stratified, from low in the
      dry north to moderately high in the moist south. In northern Senegal, along the
      Senegal River Valley and in the Ferlo semi-desert region, annual incidence is
      less than five cases per 1000 inhabitants. Many nomadic pastoralists have
      permanent dwellings in the Ferlo Desert and Senegal River Valley, but spend dry
      season in the south with their herds, returning north when the rains start,
      leading to a concern that this population could contribute to ongoing
      transmission in the north. METHODS: A modified snowball sampling survey was
      conducted at six sites in northern Senegal to determine the malaria prevention
      and treatment seeking practices and parasite prevalence among nomadic
      pastoralists in the Senegal River Valley and the Ferlo Desert. Nomadic
      pastoralists aged 6 months and older were surveyed during September and October
      2014, and data regarding demographics, access to care and preventive measures
      were collected. Parasite infection was detected using rapid diagnostic tests
      (RDTs), microscopy (thin and thick smears) and polymerase chain reaction (PCR).
      Molecular barcodes were determined by high resolution melting (HRM). RESULTS: Of
      1800 participants, 61% were male. Sixty-four percent had at least one bed net in
      the household, and 53% reported using a net the night before. Only 29% had
      received a net from a mass distribution campaign. Of the 8% (142) who reported
      having had fever in the last month, 55% sought care, 20% of whom received a
      diagnostic test, one-third of which (n = 5) were reported to be positive.
      Parasite prevalence was 0.44% by thick smear and 0.50% by PCR. None of the
      molecular barcodes identified among the nomadic pastoralists had been previously
      identified in Senegal. CONCLUSIONS: While access to and utilization of malaria
      control interventions among nomadic pastoralists was lower than the general
      population, parasite prevalence was lower than expected and sheds doubt on the
      perception that they are a source of ongoing transmission in the north. The
      National Malaria Control Program is making efforts to improve access to malaria
      prevention and case management for nomadic populations.

PMID- 29029621
TI  - Uncertainty on the effectiveness and safety of rivaroxaban in premenopausal women
      with atrial fibrillation: empirical evidence needed.
AB  - BACKGROUND: Novel anticoagulations (NOACs) are increasingly prescribed for the
      prevention of stroke in premenopausal women with atrial fibrillation. Small
      studies suggest NOACs are associated with a higher risk of abnormal uterine
      bleeds than vitamin K antagonists (VKAs). Because there is no direct empirical
      evidence on the benefit/risk profile of rivaroxaban compared to VKAs in this
      subgroup, we synthesize available indirect evidence, estimate decision
      uncertainty on the treatments, and assess whether further research in
      premenopausal women is warranted. METHODS: A Markov model with annual cycles and
      a lifetime horizon was developed comparing rivaroxaban (the most frequently
      prescribed NOAC in this population) and VKAs. Clinical event rates, associated
      quality adjusted life years, and health care costs were obtained from different
      sources and adjusted for gender, age, and history of stroke. A Monte Carlo
      simulation with 10,000 iterations was then performed for a hypothetical cohort of
      premenopausal women, estimated to be reflective of the population of
      premenopausal women with AF in The Netherlands. RESULTS: In the simulation,
      rivaroxaban is the better treatment option for the prevention of ischemic strokes
      in premenopausal women in 61% of the iterations. Similarly, this is 98% for
      intracranial hemorrhages, 24% for major abnormal uterine bleeds, 1% for minor
      abnormal uterine bleeds, 9% for other major extracranial hemorrhages, and 23% for
      other minor extracranial hemorrhages. There is a 78% chance that rivaroxaban
      offers the most quality-adjusted life years. The expected value of perfect
      information in The Netherlands equals 122 quality-adjusted life years and 22
      million Euros. CONCLUSIONS: There is a 22% risk that rivaroxaban offers a worse
      rather than a better benefit/risk profile than vitamin K antagonists in
      premenopausal women. Although rivaroxaban is preferred over VKAs in this
      population, further research is warranted, and should preferably take the shape
      of an internationally coordinated registry study including other NOACs.

PMID- 29029620
TI  - TGFbeta superfamily signaling and uterine decidualization.
AB  - Decidualization is an intricate biological process where extensive morphological,
      functional, and genetic changes take place in endometrial stromal cells to
      support the development of an implanting blastocyst. Deficiencies in
      decidualization are associated with pregnancy complications and reproductive
      diseases. Decidualization is coordinately regulated by steroid hormones, growth
      factors, and molecular and epigenetic mechanisms. Transforming growth factor beta
      (TGFbeta) superfamily signaling regulates multifaceted reproductive processes.
      However, the role of TGFbeta signaling in uterine decidualization is poorly
      understood. Recent studies using the Cre-LoxP strategy have shed new light on the
      critical role of TGFbeta signaling machinery in uterine decidualization. Herein,
      we focus on reviewing exciting findings from studies using both mouse genetics
      and in vitro cultured human endometrial stromal cells. We also delve into
      emerging mechanisms that underlie decidualization, such as non-coding RNAs and
      epigenetic modifications. We envision that future studies aimed at defining the
      interrelationship among TGFbeta signaling circuitries and their potential
      interactions with epigenetic modifications/non-coding RNAs during uterine
      decidualization will open new avenues to treat pregnancy complications associated
      with decidualization deficiencies.

PMID- 29029622
TI  - Paracrine and autocrine regulation of gene expression by Wnt-inhibitor Dickkopf
      in wild-type and mutant hepatocytes.
AB  - BACKGROUND: Cells are able to communicate and coordinate their function within
      tissues via secreted factors. Aberrant secretion by cancer cells can modulate
      this intercellular communication, in particular in highly organised tissues such
      as the liver. Hepatocytes, the major cell type of the liver, secrete Dickkopf
      (Dkk), which inhibits Wnt/ beta-catenin signalling in an autocrine and paracrine
      manner. Consequently, Dkk modulates the expression of Wnt/ beta-catenin target
      genes. We present a mathematical model that describes the autocrine and paracrine
      regulation of hepatic gene expression by Dkk under wild-type conditions as well
      as in the presence of mutant cells. RESULTS: Our spatial model describes the
      competition of Dkk and Wnt at receptor level, intra-cellular Wnt/ beta-catenin
      signalling, and the regulation of target gene expression for 21 individual
      hepatocytes. Autocrine and paracrine regulation is mediated through a feedback
      mechanism via Dkk and Dkk diffusion along the porto-central axis. Along this axis
      an APC concentration gradient is modelled as experimentally detected in liver.
      Simulations of mutant cells demonstrate that already a single mutant cell
      increases overall Dkk concentration. The influence of the mutant cell on gene
      expression of surrounding wild-type hepatocytes is limited in magnitude and
      restricted to hepatocytes in close proximity. To explore the underlying molecular
      mechanisms, we perform a comprehensive analysis of the model parameters such as
      diffusion coefficient, mutation strength and feedback strength. CONCLUSIONS: Our
      simulations show that Dkk concentration is elevated in the presence of a mutant
      cell. However, the impact of these elevated Dkk levels on wild-type hepatocytes
      is confined in space and magnitude. The combination of inter- and intracellular
      processes, such as Dkk feedback, diffusion and Wnt/ beta-catenin signal
      transduction, allow wild-type hepatocytes to largely maintain their gene
      expression.

PMID- 29029623
TI  - Hydrogen peroxide is involved in hydrogen sulfide-induced lateral root formation
      in tomato seedlings.
AB  - BACKGROUND: Both hydrogen sulfide (H2S) and hydrogen peroxide (H2O2) are
      separately regarded as a highly reactive molecule involved in root morphogenesis.
      In this report, corresponding causal link governing lateral root formation was
      investigated. METHODS: By using pharmacological, anatomic, and molecular
      approaches, evidence presented here revealed the molecular mechanism underlying
      tomato lateral root development triggered by H2S. RESULTS: A H2S donor sodium
      hydrosulfide (NaHS) triggered the accumulation of H2O2, the up-regulation of
      RBOH1 transcript, and thereafter tomato lateral root formation. Above responses
      were sensitive to the H2O2 scavenger (dimethylthiourea; DMTU) and the inhibitor
      of NADPH oxidase (diphenylene idonium; DPI), showing that the accumulations of
      H2O2 and increased RBOH1 transcript were respectively prevented. Lateral root
      primordial and lateral root formation were also impaired. Further molecular
      evidence revealed that H2S-modulated gene expression of cell cycle regulatory
      genes, including up-regulation of SlCYCA2;1, SlCYCA3;1, and SlCDKA1, and the down
      regulation of SlKRP2, were prevented by the co-treatment with DMTU or DPI. Above
      mentioned inducing phenotypes were consistent with the changes of lateral root
      formation-related microRNA transcripts: up-regulation of miR390a and miR160, and
      with the opposite tendencies of their target genes (encoding auxin response
      factors). Contrasting tendencies were observed when DMTU or DPI was added
      together. The occurrence of H2S-mediated S-sulfhydration during above responses
      was preliminarily discovered. CONCLUSIONS: Overall, these results suggested an
      important role of RBOH1-mediated H2O2 in H2S-elicited tomato lateral root
      development, and corresponding H2S-target proteins regulated at transcriptional
      and post-translational levels.

PMID- 29029624
TI  - Characteristics of spontaneous coagulase-negative staphylococcal
      spondylodiscitis: a retrospective comparative study versus Staphylococcus aureus
      spondylodiscitis.
AB  - BACKGROUND: Coagulase-negative staphylococci (CoNS) are increasingly implicated
      in recent patient series of spondylodiscitis, but there are no series of CoNS
      spondylodiscitis available. The objective of this study was to compare the
      characteristics of patients with spontaneous CoNS-spondylodiscitis with those
      patients with Staphylococcus aureus (SA) spondylodiscitis. METHODS: This was a
      retrospective single center study involving 147 spontaneous infectious
      spondylodiscitis cases observed between 2000 and 2015. The 26 cases of CoNS
      spondylodiscitis (15 confirmed) were compared with 30 cases of SA
      spondylodiscitis. CoNS infection was considered confirmed if the same CoNS was
      isolated in at least two samples at two different times. RESULT: Patients with
      CoNS-spondylodiscitis were older (70 vs. 61 years of age; p = 0.01), had
      associated cancer more often (15% vs. 0%; p = 0.04) and had a longer diagnostic
      delay (>15 days in 88% vs. 60%; p = 0.01); experienced fever less often (19% vs.
      50%; p = 0.01), and had lower white blood cell (7.6 vs. 9.9G/L; p = 0.01) and
      polymorphonuclear leucocyte counts (5.6 vs. 7.5G/L; p = 0.04). Patients with CoNS
      spondylodiscitis had less pronounced inflammatory syndrome (erythrocyte
      sedimentation rate [ESR]: 62 vs. 81 mm at 1 h; p = 0.03; CRP: 60 vs. 147 mg/L; p
      = 0.0003) and less common (ESR < 30 mm: 23% vs. 0%; p = 0.01; CRP < 10 mg/L: 23%
      vs. 0%; p = 0.005) in comparison with patients with SA infection. The infection
      entry site was most often an intravascular catheter (20% vs. 3%; p = 0.008). The
      level of positive percutaneous needle biopsies was comparable between CoNS and
      SA. Two patients who died both had SA infections. CONCLUSION: CoNS
      spondylodiscitis involved at least 10% of spontaneous spondylodiscitis cases and
      was more common in elderly patients, afflicted by comorbidities, and its
      presentation was less virulent than that of those with SA-spondylodiscitis.

PMID- 29029625
TI  - A strategy for evaluating pathway analysis methods.
AB  - BACKGROUND: Researchers have previously developed a multitude of methods designed
      to identify biological pathways associated with specific clinical or experimental
      conditions of interest, with the aim of facilitating biological interpretation of
      high-throughput data. Before practically applying such pathway analysis (PA)
      methods, we must first evaluate their performance and reliability, using datasets
      where the pathways perturbed by the conditions of interest have been well
      characterized in advance. However, such 'ground truths' (or gold standards) are
      often unavailable. Furthermore, previous evaluation strategies that have focused
      on defining 'true answers' are unable to systematically and objectively assess PA
      methods under a wide range of conditions. RESULTS: In this work, we propose a
      novel strategy for evaluating PA methods independently of any gold standard,
      either established or assumed. The strategy involves the use of two mutually
      complementary metrics, recall and discrimination. Recall measures the consistency
      of the perturbed pathways identified by applying a particular analysis method to
      an original large dataset and those identified by the same method to a sub
      dataset of the original dataset. In contrast, discrimination measures specificity
      the degree to which the perturbed pathways identified by a particular method to a
      dataset from one experiment differ from those identifying by the same method to a
      dataset from a different experiment. We used these metrics and 24 datasets to
      evaluate six widely used PA methods. The results highlighted the common challenge
      in reliably identifying significant pathways from small datasets. Importantly, we
      confirmed the effectiveness of our proposed dual-metric strategy by showing that
      previous comparative studies corroborate the performance evaluations of the six
      methods obtained by our strategy. CONCLUSIONS: Unlike any previously proposed
      strategy for evaluating the performance of PA methods, our dual-metric strategy
      does not rely on any ground truth, either established or assumed, of the pathways
      perturbed by a specific clinical or experimental condition. As such, our strategy
      allows researchers to systematically and objectively evaluate pathway analysis
      methods by employing any number of datasets for a variety of conditions.

PMID- 29029626
TI  - Higher educational attainment associated with reduced likelihood of abnormal
      cervical lesions among Zambian women - a cross sectional study.
AB  - BACKGROUND: The high burden of cervical cancer in Zambia prompted the Ministry of
      Health and partners to develop the cervical cancer prevention program in Zambia
      (CCPPZ) in 2006. Despite this intervention more women continue to die from the
      disease and there is little understanding of factors that may be linked with
      abnormal cervical lesions in the general population. We therefore examined if
      educational attainment is associated with abnormal cervical lesions among Zambian
      women aged 15 to 49 years. METHODS: This study used data from the cervical cancer
      prevention program in Zambia, where a total of 14,294 women aged 15 to 49 years
      were screened for cervical cancer at nine health facilities between October 2013
      and September 2014. The data represents women from six provinces of Zambia,
      namely Southern, Central, Copperbelt, Luapula, North-western and Eastern
      provinces. Step-wise logistic regression analysis using the Statistical Package
      for the Social Sciences (SPSS) version 21 was used to estimate adjusted odds
      ratios (AOR) and 95% confidence intervals (CIs) for educational attainment with
      presence of abnormal cervical lesions as outcome. Multiple imputation was further
      used to obtain the imputed stabilized estimates for educational attainment.
      RESULTS: The prevalence of abnormal cervical lesions, using the Visual Inspection
      with Acetic-acid (VIA) test was 10.7% (n = 1523). Educational attainment was
      inversely associated with abnormal cervical lesions (AOR = 0.75; 95% CI:0.70
      0.81, AOR = 0.74; 95% CI:0.68-0.81 and AOR = 0.46; 95% CI:0.41-0.51) among women
      with primary, secondary and tertiary education, respectively, compared to those
      with no formal education. CONCLUSION: We find reduced likelihood of abnormal
      cervical lesions in educated women, suggesting a differential imbalance with
      women who have no formal education. These findings may be a reflection of
      inequalities associated with access to cervical cancer screening, making the
      service inadequately accessible for lower educated groups. This might also
      indicate serious limitations in awareness efforts instituted in the formative
      phases of the program. These findings underline the prevailing need for urgent
      concerted efforts in repackaging cervical cancer awareness programs targeting
      women with low or no formal education in whom the risk may be even higher.

PMID- 29029627
TI  - Determinants of self-rated health among shanghai elders: a cross-sectional study.
AB  - BACKGROUND: As the most populous nation in the world, China has now becoming an
      emerging ageing society. Shanghai is the first city facing the challenge of
      ageing demographics. Against this background, a study that employs self-rated
      health (SRH) assessment system was designed to explore the health status of
      Shanghai elders, and learn their attitudes toward health issues; as well as to
      investigate the determinants of SRH among Shanghai elders. Understanding SRH is
      crucial for finding appropriate solutions that could effectively tackle the
      increasing eldercare demand. METHODS: This study adopted a quantitative research
      strategy. Using a multistage stratified cluster sampling method, we conducted a
      questionnaire survey in August 2011 in Shanghai, which collected 2001 valid
      survey responses. SRH assessments were categorized by five levels: very good,
      fairly good, average, fairly poor, or poor. The respondents' functional status
      was evaluated using the Barthel index of activities for daily living. In the data
      analysis, we used chi-squared test to determine differences in socio-demographic
      characteristics among various groups. Along with statistics, several logistic
      regression models were designed to determine the associations between internal
      influence factors and SRH. RESULTS: Younger age (chi2 = 27.5, p < 0.05), male sex
      (chi2 = 11.5, p < 0.1), and living in the suburbs (chi2 = 55.1, p < 0.05) were
      associated with better SRH scores. Higher SRH scores were also linked with health
      behaviour of the respondents; namely, do not smoke (chi2 = 18.0, p < 0.1), do not
      drink (chi2 = 18.6, p < 0.1), or engage in regular outdoor activities (chi2 =
      69.3, p < 0.05). The respondents with better social support report higher SRH
      scores than those without. Respondents' ability to hear (chi2 = 38.7, p < 0.05),
      speak (chi2 = 16.1, p < 0.05) and see (chi2 = 78.3, p < 0.05) impacted their SRH
      scores as well. Meanwhile, chronic illness except asthma was a major influence
      factor in low SRH score. Applying multiple regression models, a series of
      determinants were analysed to establish the extent to which they contribute to
      SRH. The impact of these variables on SRH scores were 6.6% from socio-demographic
      and health risk behaviours, 2.4% from social support, 8.5% from mental health,
      20% from physical conditions, and13% from chronic diseases. CONCLUSIONS: This is
      the first study that examines the determinants of SRH among Shanghai elders.
      Nearly 40% of our study's respondents reported their health status as "good". The
      main determinants of SRH among elders include living condition, health risk
      behaviour, social support, health status, and the economic status of the
      neighbourhood.

PMID- 29029630
TI  - Correction to: Correlation of CSF flow using phase-contrast MRI with
      ventriculomegaly and CSF opening pressure in mucopolysaccharidoses.
AB  - After publication of the article [1], it has been brought to our attention that
      the full funding acknowledgement is missing from the original article.

PMID- 29029628
TI  - Erythropoietin reduces experimental autoimmune encephalomyelitis severity via
      neuroprotective mechanisms.
AB  - BACKGROUND: Treatment with erythropoietin (Epo) in experimental autoimmune
      encephalomyelitis (EAE), the rodent model of multiple sclerosis (MS), has
      consistently been shown to ameliorate disease progression and improve overall
      outcome. The effect has been attributed to modulation of the immune response
      and/or preservation of the central nervous system (CNS) tissue integrity. It
      remains unclear, however, if (a) Epo acts primarily in the CNS or the periphery
      and if (b) Epo's beneficial effect in EAE is mainly due to maintaining CNS tissue
      integrity or to modulation of the immune response. If Epo acts primarily by
      modulating the immune system, where is this modulation required? In the
      periphery, the CNS or both? METHODS: To address these questions, we used two well
      characterized transgenic mouse strains that constitutively overexpress
      recombinant human Epo (rhEpo) either systemically (tg6) or in CNS only (tg21) in
      a MOG-induced EAE model. We assessed clinical severity, disease progression,
      immunomodulation, and CNS tissue integrity, including neuronal survival. RESULTS:
      Although disease onset remained unaffected, EAE progression was alleviated in
      transgenic animals compared to controls with both lines performing equally well
      showing that expression of Epo in the periphery is not required; Epo expression
      in the CNS is sufficient. Immunomodulation was observed in both strains but
      surprisingly the profile of modulation differed substantially between strains.
      Modulation in the tg21 strain was limited to a reduction in macrophages in the
      CNS, with no peripheral immunomodulatory effects observed. In contrast, in the
      tg6 strain, macrophages were upregulated in the CNS, and, in the periphery of
      this strain, T cells and macrophages were downregulated. The lack of a consistent
      immunomodulatory profile across both transgenic species suggests that
      immunomodulation by Epo is unlikely to be the primary mechanism driving
      amelioration of EAE. Finally, CNS tissue integrity was affected in all strains.
      Although myelin appeared equally damaged in all strains, neuronal survival was
      significantly improved in the spinal cord of tg21 mice, indicating that Epo may
      ameliorate EAE predominantly by protecting neurons. CONCLUSIONS: Our data
      suggests that moderate elevated brain Epo levels provide clinically significant
      neuroprotection in EAE without modulation of the immune response making a
      significant contribution.

PMID- 29029629
TI  - Effects of age and gender on reference levels of biomarkers comprising the
      pediatric Renal Activity Index for Lupus Nephritis (p-RAIL).
AB  - BACKGROUND: Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune
      disease that disproportionately effects women and children of minorities. Renal
      involvement (lupus nephritis, or LN) occurs in up to 80% of children with SLE and
      is a major determinant of poor prognosis. We have developed a non-invasive
      pediatric Renal Activity Index for Lupus (p-RAIL) that consists of laboratory
      measures that reflect histologic LN activity. These markers are neutrophil
      gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1),
      monocyte chemotactic protein (MCP-1), adiponectin (APN), ceruloplasmin (CP) and
      hemopexin (HPX). A major gap in the knowledge base and a barrier to clinical
      utility is how these markers behave in healthy children. We set out to establish
      a reference range for the p-RAIL markers in a population of healthy children, and
      to determine if levels of these markers fluctuate with age or gender. METHODS:
      Urine was collected from 368 healthy children presenting to Cincinnati Children's
      primary care clinic for well child visits and assayed for NGAL, KIM-1, MCP-1,
      APN, CP and HPX using commercially available kits or assay materials. RESULTS:
      Specimens were grouped by age (0-5 years (n = 94); 5-10 (n = 89); 10-15 (n = 93);
      15-20 (n = 91)) and gender (M = 184, F = 184). For age and gender comparisons,
      values were log transformed prior to analysis. The medians (minimums, maximums)
      of each marker in the combined population were as follows: NGAL 6.65 (0.004,
      391.52) ng/ml, KIM-1416.84 (6.22, 2512.43) pg/ml, MCP-1209.36 (9.49, 2237.06)
      pg/ml, APN 8.05 (0.07, 124.50) ng/ml, CP 465.15 (8.02, 7827.00) ng/ml, HPX 588.70
      (6.85, 17,658.40)ng/ml. All p-RAIL biomarkers but adiponectin had weak but
      significant positive correlations with age, with NGAL being the strongest (r =
      0.33, p < 0.001). For gender comparisons, NGAL, CP and HPX were elevated in
      females vs males (86%, p < 0.0001; 3%, p = 0.007, and 5%, p = 0.0005 elevation of
      the log transformed mean, respectively). CONCLUSIONS: We have established a
      reference range for the p-RAIL biomarkers and have highlighted age and gender
      differences. This information is essential for rational interpretation of studies
      and clinical trials utilizing the p-RAIL algorithm.

PMID- 29029631
TI  - Neurotrophic support by traumatized muscle-derived multipotent progenitor cells:
      Role of endothelial cells and Vascular Endothelial Growth Factor-A.
AB  - BACKGROUND: Adult mesenchymal stem cells (MSCs) have been shown to increase nerve
      regeneration in animal models of nerve injury. Traumatized muscle-derived
      multipotent progenitor cells (MPCs) share important characteristics with MSCs and
      are isolated from severely damaged muscle tissue following surgical debridement.
      Previous investigations have shown that MPCs may be induced to increase
      production of several neurotrophic factors, suggesting the possible utility of
      autologous MPCs in peripheral nerve regeneration following injury. Recent
      findings have also shown that components of the vascular niche, including
      endothelial cells (ECs) and vascular endothelial growth factor (VEGF)-A, regulate
      neural progenitor cells and sensory neurons. METHODS: In this study, we have
      investigated the neuroinductive activities of MPCs, particularly MPC-produced
      VEGF-A, in the context of an aligned, neuroconductive nerve guide conduit and the
      endothelial component of the vascular system. Embryonic dorsal root ganglia (DRG)
      seeded on poly-epsilon-caprolactone aligned nanofibrous scaffold (NF) constructs
      and on tissue culture plastic, were cocultured with induced MPCs or treated with
      their conditioned medium (MPC-CM). RESULTS: Increased neurite extension was
      observed on both NF and tissue culture plastic in the presence of MPC-CM versus
      cell-free control CM. The addition of CM from ECs significantly increased the
      neurotrophic activity of induced MPC-CM, suggesting that MPC and EC neurotrophic
      activity may be synergistic. Distinctly higher VEGF-A production was seen in MPCs
      following neurotrophic induction versus culture under normal growth conditions.
      Selective removal of VEGF-A from MPC-CM reduced the observed DRG neurite
      extension length, indicating VEGF-A involvement in neurotrophic activity of the
      CM. CONCLUSIONS: Taken together, these findings suggest the potential of MPCs to
      encourage nerve growth via a VEGF-A-dependent action, and the use of MPC-CM or a
      combination of MPC and CM from ECs for peripheral nerve repair in conjunction
      with NFs in a nerve guide conduit. Due to the ease of use, application of
      bioactive agents derived from cultured cells to enhance neurotrophic support
      presents a promising line of research into peripheral nerve repair.

PMID- 29029632
TI  - Fatal haemorrhage and neoplastic thrombosis in a captive African lion (Panthera
      leo) with metastatic testicular sex cord-stromal tumour.
AB  - BACKGROUND: The study of neoplasia in wildlife species contributes to the
      understanding of cancer biology, management practices, and comparative pathology.
      Higher frequencies of neoplasms among captive non-domestic felids have been
      reported most commonly in aging individuals. However, testicular tumours have
      rarely been reported. This report describes a metastatic testicular sex cord
      stromal tumour leading to fatal haemorrhage and thrombosis in a captive African
      lion (Panthera leo). CASE PRESENTATION: During necropsy of a 16-year-old male
      African lion, the left testicle and spermatic cord were found to be intra
      abdominal (cryptorchid), semi-hard and grossly enlarged with multiple pale-yellow
      masses. Encapsulated haemorrhage was present in the retroperitoneum around the
      kidneys. Neoplastic thrombosis was found at the renal veins opening into the
      caudal vena cava. Metastases were observed in the lungs and mediastinal lymph
      nodes. Histology revealed a poorly differentiated pleomorphic neoplasm comprised
      of round to polygonal cells and scattered spindle cells with eosinophilic
      cytoplasm. An immunohistochemistry panel of inhibin-alpha, Ki-67, human placental
      alkaline phosphatase, cytokeratin AE1/AE3, cKit, vimentin and S100 was conducted.
      Positive cytoplasmic immunolabeling was obtained for vimentin and S100.
      CONCLUSIONS: The gross, microscopic and immunohistochemical findings of the
      neoplasm were compatible with a poorly differentiated pleomorphic sex cord
      stromal tumour. Cause of death was hypovolemic shock from extensive
      retroperitoneal haemorrhage and neoplastic thrombosis may have contributed to the
      fatal outcome. To our knowledge, this is the first report of sex cord-stromal
      tumour in non-domestic felids.

PMID- 29029633
TI  - Pattern of improvement in upper limb pointing task kinematics after a 3-month
      training program with robotic assistance in stroke.
AB  - BACKGROUND: When exploring changes in upper limb kinematics and motor impairment
      associated with motor recovery in subacute post stroke during intensive therapies
      involving robot-assisted training, it is not known whether trained joints improve
      before non-trained joints and whether target reaching capacity improves before
      movement accuracy. METHODS: Twenty-two subacute stroke patients (mean delay post
      stroke at program onset 63 +/- 29 days, M2) underwent 50 +/- 17 (mean +/- SD) 45
      min sessions of robot-assisted (InMotionTM) shoulder/elbow training over 3
      months, in addition to conventional occupational therapy. Monthly evaluations (M2
      to M5) included Fugl-Meyer Assessment (FM), with subscores per joint, and four
      robot-based kinematic measures: mean target distance covered, mean velocity,
      direction accuracy (inverse of root mean square error from straight line) and
      movement smoothness (inverse of mean number of zero-crossings in the velocity
      profile). We assessed delays to reach statistically significant improvement for
      each outcome measure. RESULTS: At M5, all clinical and kinematic parameters had
      markedly improved: Fugl-Meyer, +65% (median); distance covered, +87%; mean
      velocity, +101%; accuracy, +134%; and smoothness, +96%. Delays to reach
      statistical significance were M3 for the shoulder/elbow Fugl-Meyer subscore
      (+43%), M4 for the hand (+80%) and M5 for the wrist (+133%) subscores. For
      kinematic parameters, delays to significant improvements were M3 for distance
      (+68%), velocity (+65%) and smoothness (+50%), and M5 for accuracy (+134%).
      CONCLUSIONS: An intensive rehabilitation program combining robot-assisted
      shoulder/elbow training and conventional occupational therapy was associated with
      improvement in shoulder and elbow movements first, which suggests focal behavior
      related brain plasticity. Findings also suggested that recovery of movement
      quantity related parameters (range of motion, velocity and smoothness) might
      precede that of movement quality (accuracy). TRIAL REGISTRATION: EudraCT 2016
      005121-36 . Date of Registration: 2016-12-20. Date of enrolment of the first
      participant to the trial: 2009-11-24 (retrospective data).

PMID- 29029634
TI  - Is MMTV associated with human breast cancer? Maybe, but probably not.
AB  - BACKGROUND: Conflicting results regarding the association of MMTV with human
      breast cancer have been reported. Published sequence data have indicated unique
      MMTV strains in some human samples. However, concerns regarding contamination as
      a cause of false positive results have persisted. METHODS: We performed PCR
      assays for MMTV on human breast cancer cell lines and fresh frozen and formalin
      fixed normal and malignant human breast epithelial samples. Assays were also
      performed on peripheral blood mononuclear cells from volunteer blood donors and
      subjects at risk for human retroviral infections. In addition, assays were
      performed on DNA samples from wild and laboratory mice. Sequencing of MMTV
      positive samples from both humans and mice were performed and phylogenetically
      compared. RESULTS: Using PCR under rigorous conditions to prevent and detect
      "carryover" contamination, we did detect MMTV DNA in human samples, including
      breast cancer. However, the results were not consistent and seemed to be an
      artifact. Further, experiments indicated that the probable source of false
      positives was murine DNA, containing endogenous MMTV, present in our building.
      However, comparison of published and, herein, newly described MMTV sequences with
      published data, indicates that there are some very unique human MMTV sequences in
      the literature. CONCLUSION: While we could not confirm the true presence of MMTV
      in our human breast cancer subjects, the data indicate that further, perhaps more
      traditional, retroviral studies are warranted to ascertain whether MMTV might
      rarely be the cause of human breast cancer.

PMID- 29029635
TI  - Individual signatures and environmental factors shape skin microbiota in healthy
      dogs.
AB  - BACKGROUND: The individual, together with its environment, has been reported as
      the main force driving composition and structure of skin microbiota in healthy
      dogs. Therefore, one of the major concerns when analyzing canine skin microbiota
      is the likely influence of the environment. Despite the dense fur covering,
      certain skin diseases exhibit differential prevalence among skin sites, dog
      breeds, and individuals. RESULTS: We have characterized the normal variability of
      dog skin microbiota in a well-controlled cohort of a large number of Golden
      Labrador Retriever crossed dogs (N = 35) with similar ages, related genetic
      background, and a shared environment. We found that the individual drives the
      skin microbiota composition and structure followed by the skin site. The main
      bacterial classes inhabiting dog skin in this cohort are Gammaproteobacteria and
      Bacilli. We also detected bacteria associated to the environment on different dog
      skin sites that could be reflecting the different degrees of exposure of each
      skin site and each dog. Network analyses elucidated bacterial interactions within
      and between skin sites, especially in the chin, abdomen, axilla, and perianal
      region, with the highly shared interactions probably representing an anatomical,
      behavioral, or environmental component. When analyzing each skin site
      independently to assess host-specific factors, we found that temporality (season
      of birth and time spent in the kennel) affected all the skin sites and specially
      the inner pinna. The most abundant taxon driving this difference was
      Sphingomonas. We also found taxonomic differences among male and female dogs on
      the abdomen, axilla, and back. CONCLUSIONS: We observed a large inter-individual
      variability and differences among skin sites. Host-specific variables, such as
      temporality or sex, were also shaping skin microbiota of healthy dogs, even in an
      environmental homogenous cohort.

PMID- 29029637
TI  - Drug resistance patterns following pharmacy stock shortage in Nigerian
      Antiretroviral Treatment Program.
AB  - BACKGROUND: For patients on antiretroviral therapy (ART), treatment interruptions
      can impact patient outcomes and result in the accumulation of drug resistance
      mutations leading to virologic failure. There are minimal published data on the
      impact of an ART stock shortage on development of drug resistance mutations
      (DRMs). In this report, we evaluate data from patients enrolled in the Government
      of Nigeria National ART Program that were receiving treatment at the time of a
      national drug shortage in late 2003. METHODS: We conducted a cross-sectional
      evaluation of samples collected between December 2004 and August 2005 from ART
      patients in virologic failure that either had a treatment interruption or did not
      during the late 2003 drug shortage period at the Jos University Teaching Hospital
      (JUTH). Plasma virus was genotyped, sequence data were edited and analyzed, and
      mutation profiles were categorized to evaluate predicted drug susceptibility.
      Data were analyzed to examine factors associated with development of resistance
      mutations. A genotypic sensitivity score to the alternate recommended regimen was
      computed to assess drug susceptibility if regimens were changed. RESULTS: A total
      of 56 patients were included in this evaluation (28 interrupted, 28
      uninterrupted). Patients in the interrupted group had more DRMs than those in the
      uninterrupted group (p < 0.001); interrupted patients were more likely than
      uninterrupted patients to have one or more TAM-2 mutations (57.1% interrupted vs.
      21.3% uninterrupted; p = 0.04). There was a statistically significant difference
      in resistance to both d4T (53.7% interrupted vs. 17.9 uninterrupted; p = 0.011)
      and AZT (64.3% interrupted vs. 25.0% uninterrupted; p = 0.003) by drug
      interruption status. Examining genotypic sensitivity scores, we found that 67.9%
      of the interrupted patients, as compared to 25.0% of the uninterrupted patients,
      did not have full susceptibility to one drug in the regimen to which guidelines
      recommended they be switched (p = 0.001). DISCUSSION: In this small observational
      study, we found evidence of a difference in resistance profiles and ART
      susceptibility between those that were stocked-out of drug versus those that were
      not. We believe that these data are relevant for many other low- and middle
      income countries (LMIC) that also experienced similar ART shortages as they
      rapidly scaled up their national programs.

PMID- 29029636
TI  - Gene expression modules in primary breast cancers as risk factors for
      organotropic patterns of first metastatic spread: a case control study.
AB  - BACKGROUND: Metastases from primary breast cancers can involve single or multiple
      organs at metastatic disease diagnosis. Molecular risk factors for particular
      patterns of metastastic spread in a clinical population are limited. METHODS: A
      case-control design including 1357 primary breast cancers was used to study three
      distinct clinical patterns of metastasis, which occur within the first six months
      of metastatic disease: bone and visceral metasynchronous spread, bone-only, and
      visceral-only metastasis. Whole-genome expression profiles were obtained using
      whole genome (WG)-DASL assays from formalin-fixed paraffin-embedded (FFPE)
      samples. A systematic protocol was developed for handling FFPE samples together
      with stringent data quality controls to identify robust expression profiling
      data. A panel of published and novel gene sets were tested for association with
      these specific patterns of metastatic spread and odds ratios (ORs) were
      calculated. RESULTS: Metasynchronous metastasis to bone and viscera was found in
      all intrinsic breast cancer subtypes, while immunohistochemically (IHC)-defined
      receptor status and specific IntClust subgroups were risk factors for visceral
      only or bone-only first metastases. Among gene modules, those related to
      proliferation increased the risk of metasynchronous metastasis (OR (95% CI) = 2.3
      (1.1-4.8)) and visceral-only first metastasis (OR (95% CI) = 2.5 (1.2-5.1)) but
      not bone-only metastasis (OR (95% CI) = 0.97 (0.56-1.7)). A 21-gene module (BV)
      was identified in estrogen-receptor-positive breast cancers with metasynchronous
      metastasis to bone and viscera (area under the curve = 0.77), and its expression
      increased the risk of bone and visceral metasynchronous spread in this
      population. BV was further orthogonally validated with NanoString nCounter in
      primary breast cancers, and was reproducible in their matched lymph nodes
      metastases and an external cohort. CONCLUSION: This case-control study of WG-DASL
      global expression profiles from FFPE tumour samples, after careful quality
      control and RNA selection, revealed that gene modules in the primary tumour have
      differing risks for clinical patterns of metasynchronous first metastases.
      Moreover, a novel gene module was identified as a putative risk factor for
      metasynchronous bone and visceral first metastatic spread, with potential
      implications for disease monitoring and treatment planning.

PMID- 29029638
TI  - Indoor microbiota in severely moisture damaged homes and the impact of
      interventions.
AB  - BACKGROUND: The limited understanding of microbial characteristics in moisture
      damaged buildings impedes efforts to clarify which adverse health effects in the
      occupants are associated with the damage and to develop effective building
      intervention strategies. The objectives of this current study were (i) to
      characterize fungal and bacterial microbiota in house dust of severely moisture
      damaged residences, (ii) to identify microbial taxa associated with moisture
      damage renovations, and (iii) to test whether the associations between the
      identified taxa and moisture damage are replicable in another cohort of homes. We
      applied bacterial 16S rRNA gene and fungal ITS amplicon sequencing complemented
      with quantitative PCR and chemical-analytical approaches to samples of house
      dust, and also performed traditional cultivation of bacteria and fungi from
      building material samples. RESULTS: Active microbial growth on building materials
      had significant though small influence on the house dust bacterial and fungal
      communities. Moisture damage interventions-including actual renovation of damaged
      homes and cases where families moved to another home-had only a subtle effect on
      bacterial community structure, seen as shifts in abundance weighted bacterial
      profiles after intervention. While bacterial and fungal species richness were
      reduced in homes that were renovated, they were not reduced for families that
      moved houses. Using different discriminant analysis tools, we were able identify
      taxa that were significantly reduced in relative abundance during renovation of
      moisture damage. For bacteria, the majority of candidates belonged to different
      families within the Actinomycetales order. Results for fungi were overall less
      consistent. A replication study in approximately 400 homes highlighted some of
      the identified taxa, confirming associations with observations of moisture damage
      and mold. CONCLUSIONS: The present study is one of the first studies to analyze
      changes in microbiota due to moisture damage interventions using high-throughput
      sequencing. Our results suggest that effects of moisture damage and moisture
      damage interventions may appear as changes in the abundance of individual, less
      common, and especially bacterial taxa, rather than in overall community
      structure.

PMID- 29029641
TI  - Sequence-specific detection of different strains of LCMV in a single sample using
      tentacle probes.
AB  - BACKGROUND: Virus infections often result in quasispecies of viral strains that
      can have dramatic impacts on disease outcomes. However, sequencing of viruses to
      determine strain composition is time consuming and often cost-prohibitive. Rapid,
      cost-effective methods are needed for accurate measurement of virus diversity to
      understand virus evolution and can be useful for experimental systems. METHODS:
      We have developed a novel molecular method for sequence-specific detection of RNA
      virus genetic variants called Tentacle Probes. The probes are modified molecular
      beacons that have dramatically improved false positive rates and specificity in
      routine qPCR. To validate this approach, we have designed Tentacle Probes for two
      different strains of Lymphocytic Choriomeningitis Virus (LCMV) that differ by
      only 3 nucleotide substitutions, the parental Armstrong and the more virulent
      Clone-13 strain. One of these mutations is a missense mutation in the receptor
      protein GP1 that leads to the Armstrong strain to cause an acute infection and
      Clone-13 to cause a chronic infection instead. The probes were designed using
      thermodynamic calculations for hybridization between target or non-target
      sequences and the probe. RESULTS: Using this approach, we were able to
      distinguish these two strains of LCMV individually by a single nucleotide
      mutation. The assay showed high reproducibility among different concentrations of
      viral cDNA, as well as high specificity and sensitivity, especially for the Clone
      13 Tentacle Probe. Furthermore, in virus mixing experiments we were able to
      detect less than 10% of Clone-13 cDNA diluted in Armstrong cDNA. CONCLUSIONS:
      Thus, we have developed a fast, cost-effective approach for identifying Clone-13
      strain in a mix of other LCMV strains.

PMID- 29029640
TI  - Breast carcinomas with low amplified/equivocal HER2 by Ish: potential supporting
      role of multiplex ligation-dependent probe amplification.
AB  - BACKGROUND: This is a retrospective cross sectional study aimed to verify whether
      Multiplex Ligation-dependent Probe Amplification (MLPA), a quantitative molecular
      assay, may represent a valuable reflex test in breast cancer with equivocal HER2
      expression by immunohistochemistry and HER2 gene signals/nucleus (s/n) ranging
      between 4.0 and 5.9 by in situ hybridization. METHODS: A series of 170 breast
      carcinomas scored as 2+ for HER2 expression by immunohistochemistry, were
      selected from our files and analyzed in parallel by silver in situ hybridization
      and by MLPA. According to ASCO-CAP 2013 guidelines, 54/170 tumors, displaying 4.0
      5.9 HER2 gene s/n, were defined as low amplified (ratio >= 2) or equivocal (ratio
      < 2) on the basis of centromere enumeration probe 17 (CEP17) status. An
      independent set of 108 score 2+ breast cancers represented the external
      validation set. Concordance between the two techniques was assessed through the
      use of Cohen's K statistic. RESULTS: A concordance rate of 78.2% (Cohen's K
      statistic: 0,548 95% CI:[0,419-0,677]) between in situ hybridization and MLPA was
      found in the whole series of 170 cases and of 55.5% (Cohen's K statistic: -0,043
      95% CI:[-0,271-0,184]) in the 54 tumors presenting 4.0-5.9 HER2 gene s/n. By
      MLPA, we found HER2 amplification or gain in 14% of the 21 BC presenting a
      disomic status and in 18% of the 33 BC presenting a CEP17 > 2.0. These data were
      further confirmed in the external validation set. Interestingly, the 54 low
      amplified/equivocal breast carcinomas presented a frequency of hormonal receptor
      positivity significantly higher than that observed in the amplified tumors and
      similar to the non-amplified one (p = 0.016 for estrogen receptor and p = 0.001
      for progesterone receptor). CONCLUSIONS: To avoid to offer patients an
      ineffective therapy, HER2 status should be studied more thoroughly in low
      amplified and equivocal cases which can have lower response rates and shorter
      time to progression to trastuzumab. In this context, our data indicate that MLPA
      may be a reliable, objective supporting test in selecting HER2 positive breast
      cancer patients.

PMID- 29029639
TI  - Efficacy differences of electroacupuncture with single acupoint or matching
      acupoints for chemotherapy-induced nausea and vomiting: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Previous studies have shown that acupuncture is beneficial for the
      alleviation of chemotherapy-induced nausea and vomiting. However, there is a lack
      of clinical evidence concerning the effects of acupoint-matching on chemotherapy
      induced nausea and vomiting. METHODS/DESIGN: This is a parallel randomized
      controlled trial to evaluate the occurrence of nausea and vomiting after
      chemotherapy (the incidence of nausea and vomiting, frequency, VAS score, RINVR
      rating) as the main outcome for cancer. Quality of life, anxiety and depression
      scores are the secondary outcomes. Quality of life, anxiety and depression scores
      are the secondary phase. Use of remedy drugs, routine blood examination, and
      blood biochemical tests are the safety evaluation. We also compare the different
      effects of ST36 (single acupoint), CV12 (single acupoint), and ST36-CV12 matching
      groups. DISCUSSION: The results of this trial are expected to explore the effects
      of matching different acupoints and to offer biologic plausibility for the use of
      acupuncture in the treatment of chemotherapy-induced nausea and vomiting (CINV).
      TRIAL REGISTRATION: This trial is registered with clinicaltrials.gov NCT02195921
      , The date of registration was 17 July 2014.

PMID- 29029642
TI  - Post-trauma morbidity, measured as sick leave, is substantial and influenced by
      factors unrelated to injury: a retrospective matched observational cohort study.
AB  - BACKGROUND: Mortality as an endpoint has been the focus of trauma research
      whereas few studies investigate long-term outcomes in terms of morbidity. An
      adequate analysis of post-injury morbidity includes several dimensions, for this
      reason sick leave has been used as a proxy for morbidity in the current study.
      The aim of this retrospective matched observational cohort study was to
      investigate sick leave before and after trauma and factors associated with
      prolonged sick leave. METHODS: Patients from a level one trauma centre 2005-2010
      were matched in a 1:5 ratio with uninjured controls. By linkage to national
      registries, sick leave rates were compared. The association between potential
      risk factors and full-time sick leave at twelve months post injury, the primary
      end-point, was examined in trauma patients by logistic regression. RESULTS: Four
      thousand seven hundred twelve patients and 25,013 controls aged 20-63 were
      included. Trauma patients had more sick leave both before and after trauma. Age,
      psychiatric disease, low level of education, serious injury, spinal injury,
      reduced consciousness at admission, discharge destination other than home, and
      hospital length of stay >7 days were all associated with the primary end-point.
      The strongest risk factor was sick leave before trauma; this was also noted in
      the most seriously injured patients. DISCUSSION: In this retrospective matched
      observational cohort study we found a significant long-term morbidity, measured
      as sick leave, among trauma patients. Compared to controls the difference was
      maximal early after trauma and sustained throughout the follow up period. In the
      logistic regression, factors associated with the traumatic injury as well as host
      factors increased the probability of not returning to work. Full sick leavemonth
      twelve post injury was strongly associated with pre-injury sick leave but also
      with age, psychiatric comorbidity, level of education, injury severity, spinal
      injury, low GCS at admission, length of stay at hospital and discharge to other
      destination than home. CONCLUSIONS: Trauma patients suffer from significant long
      term morbidity. The sustained post-trauma morbidity is largely influenced by
      factors not related to injury per se. These insights enable identification of
      patients at risk for prolonged sick leave after trauma.

PMID- 29029645
TI  - On the implications of desexualizing vaccines against sexually transmitted
      diseases: reflections from a practicing pediatrician.
AB  - Human papillomavirus (HPV) vaccination holds great promise for drastically
      reducing the incidence of HPV-associated cancers of the genital tract, and
      possibly also certain head and neck cancers. Unfortunately, rates of HPV vaccine
      utilization among adolescents are low in many countries. Many research studies
      have identified the fact that HPV is a sexually transmitted infection as a
      barrier to higher vaccination rates. This is related to providers' and parents'
      reluctance to discuss or consider the burgeoning sexuality of their child. An
      approach suggested to overcome this barrier is to "desexualize" the vaccine. This
      entails focusing discussions and public messages on the cancer-preventing
      properties of the vaccine and ignoring or minimizing information about HPV's
      sexual transmissibility. In an article by Velan and Yadgar, the authors argue
      that this approach does more harm than good. This associated commentary offers a
      slightly different viewpoint from one who has been "in the trenches" both
      clinically and from a research standpoint for many years.

PMID- 29029644
TI  - Varying intervals of antiretroviral medication dispensing to improve outcomes for
      HIV patients (The INTERVAL Study): study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Requirements for frequent dispensing of antiretroviral therapy (ART)
      place demands on health systems and can lead to suboptimal adherence and
      disengagement in care for patients due to the time and cost of frequent clinic
      visits. Rigorous data are needed to define optimal ART dispensing strategies and
      to evaluate the impact of a longer medication supply on retention and virologic
      suppression and determine whether this strategy lowers costs for both the patient
      and the health system. To date, no randomized studies have tested the benefits of
      6-month dispensing of ART compared to 3-month and standard of care approaches.
      METHODS: This study will be an unblinded cluster-randomized, matched controlled
      trial conducted among 8200 stable, HIV-infected individuals age 18 years and
      older on ART in Malawi and Zambia, to compare three ART dispensing intervals on
      the outcomes of retention in care (primary outcome), virologic suppression, and
      cost-effectiveness. Thirty clusters will be matched according to country,
      facility type, and ART cohort size and randomized to one of three study arms:
      standard of care, 3-month dispensing, and 6-month dispensing. Study participants
      will be followed, and outcomes will be measured at 12, 24, and 36 months. A
      subset of participants (n = 240) and providers (n = 180) will also participate in
      qualitative interviews to evaluate feasibility and acceptability of different ART
      dispensing intervals. DISCUSSION: This study will be the first to compare 6-month
      and 3-month ART dispensing intervals for stable, HIV-infected individuals in
      Malawi and Zambia. We focus on outcomes relevant to country programs, including
      retention, virologic suppression, and cost-effectiveness. Results from the study
      will help resource-limited health systems better understand the full scope of
      outcomes resulting from various ART dispensing intervals and help to inform
      health policy decisions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03101592 .
      Registered on 18 March 2017. Pan African Clinical Trials, PACTR201706002336105 .
      Registered on 2 June 2017.

PMID- 29029643
TI  - An integrated methodology for assessing the impact of food matrix and
      gastrointestinal effects on the biokinetics and cellular toxicity of ingested
      engineered nanomaterials.
AB  - BACKGROUND: Engineered nanomaterials (ENMs) are increasingly added to foods to
      improve their quality, sensory appeal, safety and shelf-life. Human exposure to
      these ingested ENMs (iENMS) is inevitable, yet little is known of their hazards.
      To assess potential hazards, efficient in vitro methodologies are needed to
      evaluate particle biokinetics and toxicity. These methodologies must account for
      interactions and transformations of iENMs in foods (food matrix effect) and in
      the gastrointestinal tract (GIT) that are likely to determine nano
      biointeractions. Here we report the development and application of an integrated
      methodology consisting of three interconnected stages: 1) assessment of iENM-food
      interactions (food matrix effect) using model foods; 2) assessment of
      gastrointestinal transformations of the nano-enabled model foods using a three
      stage GIT simulator; 3) assessment of iENMs biokinetics and cellular toxicity
      after exposure to simulated GIT conditions using a triculture cell model. As a
      case study, a model food (corn oil-in-water emulsion) was infused with Fe2O3
      (Iron(III) oxide or ferric oxide) ENMs and processed using this three-stage
      integrated platform to study the impact of food matrix and GIT effects on
      nanoparticle biokinetics and cytotoxicity . METHODS: A corn oil in phosphate
      buffer emulsion was prepared using a high speed blender and high pressure
      homogenizer. Iron oxide ENM was dispersed in water by sonication and combined
      with the food model. The resulting nano-enabled food was passed through a three
      stage (mouth, stomach and small intestine) GIT simulator. Size distributions of
      nano-enabled food model and digestae at each stage were analyzed by DLS and laser
      diffraction. TEM and confocal imaging were used to assess morphology of digestae
      at each phase. Dissolution of Fe2O3 ENM along the GIT was assessed by ICP-MS
      analysis of supernatants and pellets following centrifugation of digestae. An in
      vitro transwell triculture epithelial model was used to assess biokinetics and
      toxicity of ingested Fe2O3 ENM. Translocation of Fe2O3 ENM was determined by ICP
      MS analysis of cell lysates and basolateral compartment fluid over time. RESULTS:
      It was demonstrated that the interactions of iENMs with food and GIT components
      influenced nanoparticle fate and transport, biokinetics and toxicological
      profile. Large differences in particle size, charge, and morphology were observed
      in the model food with and without Fe2O3 and among digestae from different stages
      of the simulated GIT (mouth, stomach, and small intestine). Immunoflorescence and
      TEM imaging of the cell culture model revealed markers and morphology of small
      intestinal epithelium including enterocytes, goblet cells and M cells. Fe2O3 was
      not toxic at concentrations tested in the digesta. In biokinetics studies,
      translocation of Fe2O3 after 4 h was <1% and ~2% for digesta with and without
      serum, respectively, suggesting that use of serum proteins alters iENMs
      biokinetics and raises concerns about commonly-used approaches that neglect iENM 
      food-GIT interactions or dilute digestae in serum-containing media. CONCLUSIONS:
      We present a simple integrated methodology for studying the biokinetics and
      toxicology of iENMs, which takes into consideration nanoparticle-food-GIT
      interactions. The importance of food matrix and GIT effects on biointeractions
      was demonstrated, as well as the incorporation of these critical factors into a
      cellular toxicity screening model. Standardized food models still need to be
      developed and used to assess the effect of the food matrix effects on the fate
      and bioactivity of iENMs since commercial foods vary considerably in their
      compositions and structures.

PMID- 29029646
TI  - Paretic versus non-paretic stepping responses following pelvis perturbations in
      walking chronic-stage stroke survivors.
AB  - BACKGROUND: The effects of a stroke, such as hemiparesis, can severely hamper the
      ability to walk and to maintain balance during gait. Providing support to stroke
      survivors through a robotic exoskeleton, either to provide training or daily-life
      support, requires an understanding of the balance impairments that result from a
      stroke. Here, we investigate the differences between the paretic and non-paretic
      leg in making recovery steps to restore balance following a disturbance during
      walking. METHODS: We perturbed 10 chronic-stage stroke survivors during walking
      using mediolateral perturbations of various amplitudes. Kinematic data as well as
      gluteus medius muscle activity levels during the first recovery step were
      recorded and analyzed. RESULTS: The results show that this group of subjects is
      able to modulate foot placement in response to the perturbations regardless of
      the leg being paretic or not. Modulation in gluteus medius activity with the
      various perturbations is in line with this observation. In general, the foot of
      the paretic leg was laterally placed further away from the center of mass than
      that of the non-paretic leg, while subjects spent more time standing on the non
      paretic leg. CONCLUSIONS: The findings suggest that, though stroke-related gait
      characteristics are present, the modulation with the various perturbations
      remains unaffected. This might be because all subjects were only mildly impaired,
      or because these stepping responses partly occur through involuntary pathways
      which remain unaffected by the complications after the stroke.

PMID- 29029648
TI  - Screening for Oral Cancer in a Mixed General Dental Practice.
AB  - How effectively is oral cancer screening being performed in a mixed general
      dental practice? Screening for oral cancer is a powerful tool in early detection
      and treatment of cancer. This audit aims to assess the effectiveness of oral
      cancer screening at a mixed NHS and private general dental practice in the West
      Midlands. A retrospective review of 100 case notes were audited for recording of
      soft tissue examination and social history, including alcohol consumption and
      cigarette smoking. The standards were set at 100% for both soft tissue
      examination and social history. The results showed that 100% of patients had
      received a soft tissue examination and 99% had their social history recorded. An
      attempt to eliminate the deficit to the set standard was by changing the medical
      history form to include social history. A re-audit is planned for six months'
      time.

PMID- 29029649
TI  - Chronic Facial Pain.
AB  - Orofacial pain is a common complaint with the vast majority of cases the result
      of an acute dental cause. There are, however, a number of patients who experience
      chronic orofacial pain in whom no dental cause can be found, and it is therefore
      important to identify these patients in order to avoid unnecessary dental
      procedures. Successful management of chronic orofacial pain depends on the
      correct diagnosis and appropriate interventions with a biopsychosocial approach.

PMID- 29029647
TI  - Renal manifestations of HIV during the antiretroviral era in South Africa: a
      systematic scoping review.
AB  - BACKGROUND: It is estimated that 650,000 patients may develop human
      immunodeficiency virus (HIV)-related renal disease in South Africa. South Africa
      has recently adopted WHO policy, stipulating that all HIV-infected patients have
      access to antiretroviral treatment (ART) irrespective of CD4 cell count. METHODS:
      We searched Google Scholar, PubMed, Medline, Cochrane Library, Worldcat.org and
      EBSCO host databases from July 2015 to December 2015. Eligibility criteria
      included articles pertaining to renal manifestations of HIV in South Africa from
      2004 to 2015 in adult patients (>= 18 years). We independently reviewed the
      articles for quality. Thematic content analysis was performed to identify
      patterns of renal manifestations from the included studies. The risk of bias
      (e.g. internal validity) in the included studies was evaluated using the mixed
      methods appraisal tool. RESULTS: Eleven out 21 studies were eligible for data
      extraction. The prevalence of urine abnormalities on urine dipsticks was high but
      had poor sensitivity and specificity for detecting renal impairment. Normal renal
      function occurred in 28.4 to 79% of patients, mild renal impairment occurred in
      19 to 57.1% and moderate renal impairment in 2 to 14.4%. Severe renal impairment
      occurred in 1.3% of patients. Both the Cockcroft-Gault equation (after correcting
      for bias) and the 4-variable Modification of Diet in Renal Disease equation
      (without the ethnicity factor for African Americans) have been validated for the
      estimation of glomerular filtration rate (eGFR) in Black South Africans. HIV
      associated nephropathy was the most prevalent histology seen (57.2%). Older age,
      a lower CD4 count, a low haemoglobin and a detectable viral load were associated
      with renal impairment. Renal function improved in the first year of commencing
      ART as evidenced by the regression of proteinuria and the increase in eGFR.
      CONCLUSION: The findings of the review have implications to the recently adopted
      'test and treat' approach to HIV prevention and management. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42016039270.

PMID- 29029650
TI  - Oral Ulceration: An Overview of Diagnosis and Management.
AB  - Mouth ulcers are a common complaint by patients, with individuals regularly
      presenting to primary care practitioners for diagnosis and treatment. The
      aetiology and pathogenesis of oral ulceration is, however, both varied and
      complex. This article highlights the importance of differentiating recurrent
      aphthous stomatitis (RAS) in otherwise healthy individuals from recurrent oral
      ulceration (ROU) secondary to known or unknown systemic disease. An overview of
      the diagnosis and management of such patients is provided as a framework to guide
      general dental practitioners' with clinical decision making on whether to treat
      or refer to secondary care.

PMID- 29029651
TI  - Oral Lichenoid and Lichen Planus-like Lesions.
AB  - Many red and white lesions of the mouth are clinically indistinguishable from
      those of oral lichen planus (OLP). These lesions, often referred to as oral
      lichenoid lesions (OLL), can occur as a result of contact sensitivity (lichenoid
      contact reactions), drug reactions or as part of chronic graft versus host
      disease (GVHD). Oral lesions in discoid lupus erythematosus (DLE) and systemic
      lupus erythematosus (SLE) can also have a similar clinical appearance to OLP.
      Distinguishing oral lichen planus from oral lichenoid lesions, lupus lesions, or
      other red and white lesions of the mouth can be difficult (even impossible) but
      it is important, for optimal management of each condition. All patients with red
      and white pathological lesions should be referred to an oral medicine or a local
      oral or maxillofacial surgery department, where a biopsy and other investigations
      can help to establish a diagnosis, and appropriate treatment and monitoring can
      be commenced. Dentists and other members of the dental team, such as hygienists
      and dental therapists, should also equip themselves with the knowledge to be able
      to explain different pathologies of the mouth to their patients and discuss risk
      factors.

PMID- 29029652
TI  - Oral Lichen Planus.
AB  - Lichen planus (LP) is a relatively common autoimmune T-cell-mediated disease of
      unknown aetiology affecting the mucous membranes, skin and nails. Its prevalence
      varies between 0.5 and 2.2% of the population in epidemiological studies with a
      peak incidence in the 30-60 years range and with a female predominance of 2:1.
      Mucosal lichen planus tends to follow a chronic course with acute exacerbations.
      Spontaneous remission of oral lichen planus (OLP) is uncommon, and indeed mucosal
      LP may become worse with time. In contrast, cutaneous lichen planus may follow a
      milder clinical course though some variants may be severe such as those affecting
      the palms and soles and the scalp and the genital tract in females (vulvovaginal
      gingival LP) where scarring leads to significant complications. It is important
      to identify those cases that may be drug induced or be associated with a contact
      allergic or irritant reaction (lichenoid reaction) or the rarer oral presentation
      of discoid lupus erythematosus. There is a very small risk of malignancy
      (approximately 1:200 patients/year) associated with oral lichen planus; thus
      patients should be informed that long term monitoring via their general dental
      practitioner is appropriate. This review will focus on the clinical presentation
      and management of oral lichen planus.

PMID- 29029653
TI  - An Overview of Vesicobullous Conditions Affecting the Oral Mucosa.
AB  - Vesicobullous diseases are characterised by the presence of vesicles or bullae at
      varying locations in the mucosa. The most common occurring in the oral cavity are
      mucous membrane pemphigoid (MMP) and pemphigus vulgaris (PV). Both are autoimmune
      diseases with a peak age onset of over 60 years and females are more commonly
      affected than men. This paper reviews the structure of the oral mucosa, with
      specific reference to the basement membrane zone, as well as bullous conditions
      affecting the mucosa, including PV and pemphigoid, their aetiology, clinical
      presentation, and management.

PMID- 29029654
TI  - The Clinical Presentation of Oral Potentially Malignant Disorders.
AB  - Early detection of oral cancer improves survival rates significantly, however,
      the incidence of oral cancer has continued to rise in the UK - between 2002-2012,
      it increased by more than 30%. There is currently no national screening programme
      for oral cancer, so undertaking a full examination of the oral mucosa during
      routine dental appointments is vital. Although strong evidence is still lacking,
      oral cancer is thought to be preceded by oral potential malignant disorders
      (OPMDs) or oral precancerous diseases. These mainly present as white/red lesions
      within the mouth and their clinical appearance can be challenging to diagnose
      accurately, which can lead to them being misdiagnosed as negligible problems.
      Dentists must keep up to date with OPMDs detection and ensure they are capable of
      correctly recognising lesions that carry a potential risk. This paper aims to
      provide a brief overview on OPMDs, highlighting potentially malignant disorders
      as they may present to the practitioner, showing their typical clinical
      appearance, and suggesting differential diagnosis and clinical management in
      dental practice.

PMID- 29029655
TI  - Oral Cancer Diagnosis in Primary Care.
AB  - The incidence of oral cancer in the UK is rising, with approximately 7,300 new
      cases diagnosed in 2012. The number of oral cancer cases in the UK has risen by
      more than a quarter in the last decade. Mouth cancer is within the ten most
      common cancers encountered among men in the UK. Primary care practitioners, both
      in a dental and medical setting, have a role in the early diagnosis of oral
      malignancy, and in providing patients with information regarding risk factors
      such as smoking, alcohol and betel quid use. The purpose of this paper is to
      present the epidemiology and risk factors related to oral cancer and particularly
      review the literature regarding the level of awareness and practice in primary
      care as recorded in relevant research.

PMID- 29029656
TI  - Dry Mouth and Sjogren's Syndrome: An Overview.
AB  - Dry mouth is a common condition presenting to a GP or general dental
      practitioner. The most common cause of a dry mouth is related to medication use,
      however patients with Sjogren's syndrome, a multisystem autoimmune condition, may
      present to their dentist rather than their GP complaining of dry mouth and dry
      eyes. This article explores the causes of dry mouth and how a patient can be
      investigated to find the cause of their dry mouth. An overview of Sjogren's
      syndrome, the relevant diagnostic criteria, presenting signs and symptoms,
      investigations and management principles are outlined.

PMID- 29029657
TI  - Dry Mouth and Clinical Oral Dryness Scoring Systems.
AB  - Dry mouth or xerostomia is the feeling that there is not sufficient saliva in the
      mouth. If this is present all or most of the time then it can be uncomfortable.
      It can also sometimes indicate health problems and as a result should be brought
      to the attention of a health care professional. Xerostomia does not always equate
      to hyposalivation. There are ways to assess degrees of oral dryness, namely-CODS
      (clinical oral dryness scoring) which helps to give a numerical value to the oral
      signs.

PMID- 29029658
TI  - Update on Orofacial Granulomatosis.
AB  - Orofacial granulomatosis (OFG) is a condition manifesting clinically with chronic
      swelling of the mouth and/or face, notably with swelling of the lips and oral
      mucosa, a full-thickness, erythematous gingivitis and mucosal ulceration of
      various clinical types. Some patients may also present with neurological
      findings, for example facial palsy. Biopsy of affected tissue shows lymphoedema,
      with or without granulomatous inflammation. The oral lesions in OFG are
      histologically indistinguishable from the oral lesions in Crohn's disease (CD)
      and other systemic granulomatous disorders. It is a condition which may respond
      to the exclusion of certain food-related chemicals from the diet in up to 60% of
      patients and, as such, is distinct from gastrointestinal CD. CD is a relapsing
      systemic inflammatory disease which predominantly affects the gut, and patients
      suffering from this disease frequently present with abdominal pain, fever and
      altered bowel habit. A proportion of patients with clinical OFG (without other
      systemic disease) may have asymptomatic gastrointestinal involvement or go on to
      develop gut CD suggesting an association between the two diseases. It is
      estimated that 1% of CD sufferers may have a diagnosis of OFG, but the majority
      of patients in specialist OFG clinics do not have gut symptoms.

PMID- 29029659
TI  - Real Time Optical Vascular Imaging: A Potential Technique for the Diagnosis of
      Mucosal Disease Including Early Oral Cancer.
AB  - Early detection of oropharyngeal carcinoma is imperative in order to minimise
      morbidity and increase survival rate, but most of these patients present to the
      specialist with already advanced stages of malignancy, when the prognosis is
      relatively poor. General dental practitioners and dental care professionals have
      a unique opportunity during routine examination to detect any suspicious lesions.
      However, we continue to rely mostly on conventional examination, which is known
      to have limitations. There are diagnostic adjuncts available to help detect oral
      squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD),
      such as vital staining, brush cytology and macroscopic light-based detection
      techniques, discussed elsewhere in this issue. However a recent meta-analysis
      demonstrated that these techniques are not reliable enough as standalone
      diagnostics and that conventional biopsy remains the diagnostic gold standard.
      This article shows a new imaging technique which has the potential to detect
      early signs of oral cancer. This technique is based on the use of green light
      which allows the observation of oral microvasculature. General dental
      practitioners and dental care practitioners have a privileged opportunity during
      routine examination to detect any suspicious lesions in the head and neck region
      and refer when necessary to specialist care. However, they rely mostly on
      conventional examination, which is known to be insufficient for the detection of
      early signs of malignancy. There are diagnostic adjuncts available to help detect
      oral cancer and oral premalignant disorders, such as vital staining, brush
      cytology and macroscopic light-based detection techniques, but a recent meta
      analysis has concluded that alone, these are not reliable enough to make a full
      tissue diagnosis. In the main, their value is more as a guide to indicate need
      for and to locate sites for conventional biopsy, which remains the diagnostic
      gold standard. However, biopsy also has inherent limitations such as sample
      handling and site errors and is associated with patient morbidity at every
      sampling event. The authors have developed and tested a new real-time optical
      vascular imaging technique (RTOVI) to observe the gingival microvasculature as a
      direct reporter of local tissue function and behaviour. In addition to direct
      imaging, the reliability of a potential image analysis method, developed for
      microvascular images, was assessed. The images were assessed for number of
      capillaries, capillary area (CA), total capillary area (TCA) and aspect ratio
      (AR). The mean number of capillaries found in our study (45.06 per mm2) which was
      higher than figures identified in previous 'same-location' oral mucosal studies
      (15.42 per mm2). This may reflect the wide variation between individuals and
      potentially improved resolution and contrast optics between studies. This small
      study suggests that mean values in CA, TCA and AR may be reliable parameters for
      thresholding normal values, for comparison between individuals and for the
      assessment of the microvasculature over time. This assessment of normal is
      essential to pave the way for further studies involving inflammatory and mitotic
      lesions.

PMID- 29029662
TI  - Robert Warnock: Make Sure Your Voice is Heard.

PMID- 29029661
TI  - When Enough Is Enough.

PMID- 29029664
TI  - 2017 ASCP Annual Meeting & Exhibition.

PMID- 29029663
TI  - Demystifying Probiotics: Use in the Elderly.
AB  - Pharmacists and other health care professionals can be perplexed by the growing
      body of literature regarding the use of probiotics for a variety of symptoms and
      conditions and by an increasing number of probiotic products available to
      consumers. Understanding the functions of the intestinal microbiome, the possible
      mechanisms of actions of probiotics, the research supporting or refuting
      probiotic use, and criteria for selecting a probiotic product is essential to
      making a rational recommendation for patients.

PMID- 29029665
TI  - Mohs Micrographic Surgery: Key Pharmacologic Considerations.
AB  - OBJECTIVE: To describe Mohs micrographic surgery and evaluate whether direct oral
      anticoagulants should be withheld in patients with atrial fibrillation (Afib)
      prior to the procedure and to consider what type of antibiotic prophylaxis should
      be used. SETTING: A community setting in which an elderly patient is living
      independently at home. PRACTICE DESCRIPTION: Academic-affiliated internal
      medicine clinic that cares for adult patients of all ages, including elderly
      patients living independently in their own home. The practice occasionally
      consults with geriatric specialty pharmacists to obtain drug information
      regarding drug therapy. PRACTICE INNOVATION: Identify and assess literature
      regarding therapeutic issues regarding patients with Afib, whether direct oral
      anticoagulants should be withheld prior to dermatologic surgery, and what type of
      antibiotic prophylaxis should be provided prior to the procedure. MAIN OUTCOME
      MEASUREMENTS: Highlight literature that assesses surgical bleeding risk if direct
      oral anticoagulants are continued, and alternatively, the risk of a
      thromboembolic event if discontinued; and address antibiotic prophylaxis prior to
      Mohs micrographic surgery in a patient with Afib. RESULTS: In an elderly patient
      with Afib, a pharmacist should evaluate bleeding risk if direct oral
      anticoagulants are continued, risk for stroke if anticoagulants are discontinued,
      and determine appropriate antibiotic prophylaxis prior to Mohs micrographic
      surgery. CONCLUSION: In patients with Afib treated with direct oral
      anticoagulants who will have dermatologic surgery, the bleeding risk is usually
      low, whereas risk of a possible thromboembolic event is high, and antibiotic
      prophylaxis should be done to prevent infection.

PMID- 29029666
TI  - Exercising with Veterans: How Social Interaction with a Pharmacy Student Improves
      Patient Care.
AB  - With the baby boomer population anticipated to explode between 2010 and 2030, it
      is essential that student pharmacists learn how to properly care for older
      patients. One way for pharmacy students to prepare for providing health care to
      the elderly is to partake in an Advanced Pharmacy Practice Experience (APPE)
      elective course in geriatrics. Pharmacy students, and health care professionals
      in general, have an immense amount of information available to them that is not
      found in a patient's chart or textbook, but can be uncovered through increased
      social interaction with patients, promoting the best possible care. Although
      these are not novel ideas, this article describes a unique experience I recently
      had with the veterans at the Alvin C. York Campus of the Veterans Affairs (VA)
      Tennessee Valley Healthcare System. While completing an APPE elective in
      geriatrics, I was given the opportunity to attend twice-weekly exercise classes
      with the veterans. When my preceptor first told me about this project, I was both
      excited and intrigued because I thought it would be an interesting way to
      interact with my patients, but I never imagined how much the relationships I
      formed would positively impact my ability to care for my patients.

PMID- 29029667
TI  - Prediction Accuracy of Winter-Tozer Equations to Estimate Free Phenytoin
      Concentrations in Non-Critically Ill Hospitalized Patients.
AB  - OBJECTIVE: To assess the accuracy of the standard and revised Winter-Tozer (WT)
      equations of predicting free phenytoin (PHT) concentrations in non-critically
      ill, hospitalized patients. DESIGN: Retrospective chart review. SETTING: Single
      center, large urban community hospital. PATIENTS, PARTICIPANTS: Patients with
      free PHT levels obtained during the study period were reviewed. Thirty-nine non
      critically ill, hospitalized adults met the inclusion criteria. The study
      population consisted of 77% African-Americans and 77% individuals 65 years of age
      and older. INTERVENTIONS: PHT concentrations were measured at ambient
      temperature. Predicted free PHT concentrations were estimated as 10% of
      normalized total PHT concentrations using standard or revised WT equations in two
      groups of patients with hypoalbuminemia and end-stage renal disease (ESRD). MAIN
      OUTCOME MEASURE(S): Correlation between measured versus predicted free PHT
      concentrations in patients with hypoalbuminemia or ESRD. RESULTS: Strong positive
      correlations were identified between measured and predicted free PHT
      concentrations for 27 patients with hypoalbuminemia (r [the Pearson correlation
      coefficient] = 0.96; P < 0.001) and 12 patients with ESRD (r = 0.95; P < 0.001).
      CONCLUSION: This study population represented a largely understudied population
      in this research area. Use of traditional and revised WT equations in primarily
      elderly, non-critically ill African-American populations can be considered to
      accurately predict PHT levels in populations with altered PHT albumin binding
      resulting from hypoalbuminemia or ESRD and settings where free PHT levels are not
      readily obtainable.

PMID- 29029668
TI  - The DE-PHARM Project: A Pharmacist-Driven Deprescribing Initiative in a Nursing
      Facility.
AB  - OBJECTIVE: Many residents with life-limiting illnesses are being prescribed and
      taking potentially inappropriate medications (PIMs) and questionably beneficial
      medications either near or at the end of life. These medications can contribute
      to adverse drug reactions, increase morbidity, and increase unnecessary burden
      and cost. It is crucial that the process of deprescribing be incorporated into
      the care of these residents. After developing a clinical pharmacist-driven
      deprescribing initiative in the nursing facility, the objective of this project
      was to reduce the number of PIMs via accepted recommendations from the clinical
      pharmacist to the primary team. DESIGN/SETTING/PARTICIPANTS: The Discussion to
      Ensure the Patient-centered, Health-focused, prognosis-Appropriate, and Rational
      Medication regimen (DE-PHARM) quality improvement-approved project was conducted
      in an urban, academic nursing facility in Pittsburgh, Pennsylvania. The pilot
      phase occurred between October 2015 and April 2016. To be included in this study,
      participants had to be a custodial resident of the nursing facility with a
      previously documented comfort-focused treatment plan. All medications used for
      the management of chronic comorbid diseases were eligible for review. RESULTS:
      Forty-seven residents managed by eight different primary teams met inclusion
      criteria. Thirty-nine recommendations for 23 residents were made by the clinical
      pharmacist, with an average of 0.82 and range of 0-5 recommendations per
      resident, respectively. Of those, only 10 (26%) were accepted, 1 (3%) was
      modified, 3 (7%) were rejected, and 25 (64%) had no response within the 120-day
      response period. Additionally, two residents died during the project, and one
      resident was readmitted to the hospital for a prolonged period of time.
      CONCLUSION: The pilot phase of the DE-PHARM project, a clinical pharmacist-driven
      deprescribing initiative, was designed and assessed. This project demonstrated
      the feasibility of such an initiative. Because of the complexity of such a
      process, special attention must be paid to eligible residents and medications,
      the need for interprofessional collaboration, and the operational process. This
      project is ongoing in other nursing facilities in Western Pennsylvania.

PMID- 29029669
TI  - CMS Moves Toward a New Payment System for Nursing Facilities.

PMID- 29029670
TI  - ?

PMID- 29029671
TI  - Presidential Address: Embracing the Repulsive: The Case for Disgust as a
      Functionally Central Emotional State in the Theory, Practice, and Dissemination
      of Cognitive-Behavior Therapy.
AB  - Disgust is a primary emotion, but it is also understudied in general, and in
      psychopathology in particular. Disgust plays a potential role in the reluctance
      of many non-scientifically minded practitioners from adopting evidence-based
      methods of treatment. This article summarizes findings from psychopathology
      research and treatment, and highlights basic science that potentially accounts
      for the hesitancy for some therapists to adopt evidence-based methods. Several
      recommendations are provided for future research in disgust related to both
      psychopathology and dissemination research.

PMID- 29029672
TI  - Emotion Regulation Protects Against Recurrence of Depressive Symptoms Following
      Inpatient Care for Major Depressive Disorder.
AB  - Relapse following response in psychotherapy for major depressive disorder (MDD)
      is a major concern. Emotion regulation (ER) has been discussed as a putative
      emerging and maintaining factor for depression. The purpose of the present study
      was to examine whether ER protects against recurrence of depression over and
      above residual symptoms of depression following inpatient care for MDD. ER skills
      (ERSQ-ES) and depression (HEALTH-49) were assessed in 193 patients with MDD (age,
      M = 47.4, SD = 9.6, 75.1% female, 100% Caucasian) at treatment discontinuation, 3
      and 12 months after treatment. Multiple hierarchical regressions were used to
      examine general and specific ER as predictors of depressive symptoms at follow
      ups. Higher general ER predicted lower depression over and beyond residual
      symptoms of depression at 3-month follow-up among treatment responders but not
      among treatment nonresponders. With regard to specific ER skills, readiness to
      confront and acceptance of undesired emotions predicted lower depressive symptoms
      beyond residual symptoms of depression 12 months, respectively 3 and 12 months
      after treatment. Findings of the present study indicate that targeting general ER
      might be more important for remitted and less important for nonremitted patients.
      Enhancing ER should hence be realized in a sequential treatment design, in which
      a continuation phase treatment with a specific focus on ER directly follows, once
      patients sufficiently responded to treatment. Acceptance of undesired emotion and
      readiness to confront situations that cue these emotions appear to be
      particularly important for protecting against recurrence of depression. Future
      research should clarify whether findings can be generalized to outpatient care.

PMID- 29029673
TI  - Emotion Regulation in Borderline Personality Disorder: An Experimental
      Investigation of the Effects of Instructed Acceptance and Suppression.
AB  - Difficulties with emotion regulation are central to borderline personality
      disorder (BPD). Recent research suggests that avoidance of emotions in general,
      and emotion suppression specifically, may be commonly used among those who meet
      criteria for the disorder. Contemporary behavioral interventions for BPD
      incorporate cognitive and behavioral skills to increase emotional experiencing
      and acceptance while decreasing behaviors that function to escape or avoid from
      emotions. Few studies, however, have experimentally examined the effects of
      instructed emotion suppression and acceptance in BPD. The present study examined
      the effects of instructed use of different emotion regulation strategies on
      emotions, psychophysiology, and behavior in BPD. Participants with BPD, major
      depressive disorder (MDD), and nonpsychiatric controls (N = 193) were randomly
      assigned to either suppress or accept emotions during an audio recording of a
      social rejection scenario, and completed a behavioral measure of distress
      tolerance. BPD participants exhibited greater heart rate variability in the
      acceptance (vs. suppression) condition; this pattern was not evident within the
      other groups. These results suggest that deliberate use of acceptance-based
      emotion regulation strategies may have unique physiological effects among
      individuals with BPD.

PMID- 29029674
TI  - Patterns of Anxious Arousal During a Speech Task Between Nonanxious Controls and
      Individuals With Social Anxiety Disorder Pre- and Posttreatment.
AB  - Although research indicates that anxious arousal in response to feared stimuli is
      related to treatment outcome (Heimberg et al., 1990), less is known about the
      patterns of anxious arousal. We identified patterns of anxious arousal in
      individuals with social anxiety disorder (SAD) at pre- (n= 61) and posttreatment
      (n= 40; 12-session CBGT, Heimberg & Becker, 2002), and in non-anxious controls
      (NACs; n= 31) using an assessment speech task administered at pretreatment (SAD)
      or the pretreatment equivalent (NACs), as well as at posttreatment (SAD only). We
      identified nine patterns of anxious arousal across groups that we further
      clustered into three groups: fear habituation, fear plateau, and fear increase.
      Chi-square and adjusted standardized residual analyses revealed that individuals
      in the pretreatment SAD group displayed the fear habituation patterns
      significantly more than chance and the fear plateau patterns significantly less
      than chance. In contrast, NACs displayed the fear plateau patterns significantly
      more than chance and the fear habituation patterns significantly less than
      chance. At posttreatment, treatment non-responders displayed fear habituation
      patterns significantly more than chance, whereas treatment responders displayed
      the fear habituation patterns significantly less than chance. Findings indicate
      that fear habituation during an anxiety-provoking assessment task is not
      necessary for treatment response.

PMID- 29029676
TI  - Childhood ADHD and Negative Self-Statements: Important Differences Associated
      With Subtype and Anxiety Symptoms.
AB  - The current study examined the role negative self-statements have on the
      comorbidity between anxious symptomatology and ADHD-combined presentation (ADHD
      C) and ADHD-predominantly inattentive (ADHD-I). A total of 114 children and
      adolescents with ADHD (M age = 10.15; SD = 2.30; range = 7-16) from a clinic
      referred sample were grouped based on a semistructured diagnostic interview and
      consensus approach (ADHD-C, n = 62; ADHD-I, n = 52). Negative self-statements
      were measured using the Children's Automatic Thoughts Scale and the total score
      from the Multidimensional Anxiety Scale for Children was used to measure anxious
      symptomatology. Findings indicated youth diagnosed with ADHD-C, compared to those
      diagnosed with ADHD-I, had more frequent personal failure (Cohen's d =.40) and
      hostile intent negative self-statements (Cohen's d =.47). The association of ADHD
      subtype and negative self-statements was moderated by anxiety; negative self
      statements of personal failure were highest in anxious ADHD-C children (beta
      =.31). A second sample of 137 children and adolescents (M age = 10.61; SD = 2.26;
      range = 7-16) from a larger clinic-referred sample was utilized to replicate our
      results dimensionally. Results indicated that both hyperactivity/impulsivity
      (beta = .23, p < .01) and the interaction of hyperactivity/impulsivity and
      anxiety (beta = .17, p < .05) were significant predictors of negative self
      statements regarding personal failure, while holding child age, child gender,
      oppositional symptoms, and inattention constant. In all, negative self-statements
      should be considered in the treatment and assessment of ADHD with particular
      attention paid to ADHD subtype and internalizing comorbidity.

PMID- 29029675
TI  - A Meta-Analysis of Compassion-Based Interventions: Current State of Knowledge and
      Future Directions.
AB  - OBJECTIVE: Scientific research into compassion has burgeoned over the past 20
      years and interventions aiming to cultivate compassion towards self and others
      have been developed. This meta-analysis examined the effects of compassion-based
      interventions on a range of outcome measures. METHOD: Twenty-one randomized
      controlled trials (RCTs) from the last 12 years were included in the meta
      analysis, with data from 1,285 participants analyzed. Effect sizes were
      standardized mean differences calculated using the difference in pre-post change
      in the treatment group and control group means, divided by the pooled pre
      intervention standard deviation. RESULTS: Significant between-group differences
      in change scores were found on self-report measures of compassion (d = 0.55, k =
      4, 95% CI [0.33-0.78]), self-compassion (d = 0.70, k = 13, 95% CI [0.59-0.87]),
      mindfulness (d = 0.54, k = 6, 95% CI [0.38-0.71]), depression (d = 0.64, k = 9,
      95% CI [0.45-0.82]), anxiety (d = 0.49, k = 9, 95% CI [0.30-0.68]), psychological
      distress (d = 0.47, k = 14, 95% CI [0.19-0.56]), and well-being (d = 0.51, k = 8,
      95% CI [0.30-0.63]). These results remained when including active control
      comparisons. Evaluations of risk of bias across studies pointed towards a
      relative lack of publication bias and robustness of findings. However, the
      evidence base underpinning compassion interventions relies predominantly on small
      sample sizes. CONCLUSIONS: Future directions are provided for compassion
      research, including the need for improved methodological rigor, larger scale
      RCTs, increased specificity on the targets of compassion, and examination of
      compassion across the lifespan. Although further research is warranted, the
      current state of evidence highlights the potential benefits of compassion-based
      interventions on a range of outcomes.

PMID- 29029677
TI  - Exposure-Based Therapy for Symptom Preoccupation in Atrial Fibrillation: An
      Uncontrolled Pilot Study.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia. Patients often
      experience a range of symptoms resulting in a markedly reduced quality of life,
      and commonly show symptom preoccupation in terms of avoidance and control
      behaviors. Cognitive behavior therapy (CBT) has been shown to improve symptom
      burden and quality of life in other somatic disorders, but has never been
      evaluated in patients with AF. The purpose of this study was to evaluate the
      potential efficacy and feasibility of an AF-specific CBT protocol in an
      uncontrolled pilot study. The study included 19 patients with symptomatic
      paroxysmal (intermittent) atrial fibrillation who were assessed pre- and
      posttreatment and at 6-month follow-up. The CBT lasted 10 weeks and included
      exposure to physical sensations similar to AF symptoms, exposure to avoided
      situations or activities, and behavioral activation. We observed large within
      group improvements on the primary outcome AF-specific quality of life measurement
      AFEQT posttreatment (Cohen's d = 1.54; p < . 001) and at 6-month follow-up (d =
      1.15; p < . 001). We also observed improvements in self-reported frequency and
      severity of AF symptoms. All participants completed the treatment and treatment
      satisfaction was high. This study demonstrates the potential efficacy and
      feasibility of a novel CBT approach to reduce symptoms and increase quality of
      life in AF patients.

PMID- 29029678
TI  - Positive and Negative Affect as Links Between Social Anxiety and Depression:
      Predicting Concurrent and Prospective Mood Symptoms in Unipolar and Bipolar Mood
      Disorders.
AB  - The co-occurrence of social anxiety and depression is associated with increased
      functional impairment and a more severe course of illness. Social anxiety
      disorder is unique among the anxiety disorders in sharing an affective profile
      with depression, characterized by low levels of positive affect (PA) and high
      levels of negative affect (NA). Yet it remains unclear how this shared affective
      profile contributes to the covariation of social anxiety and depressive symptoms.
      We examined whether self-reported PA and NA accounted for unique variance in the
      association between social anxiety and depressive symptoms across three groups
      (individuals with remitted bipolar disorder, type I [BD; n = 32], individuals
      with remitted major depressive disorder [MDD; n = 31], and nonpsychiatric
      controls [n = 30]) at baseline and follow-ups of 6 and 12 months. Low levels of
      PA, but not NA, accounted for unique variance in both concurrent and prospective
      associations between social anxiety and depression in the BD group; in contrast,
      high levels of NA, but not PA, accounted for unique variance in concurrent and
      prospective associations between social anxiety and depression in the MDD group.
      Limitations include that social anxiety and PA/NA were assessed concurrently and
      all measurement was self-report. Few individuals with MDD/BD met current
      diagnostic criteria for social anxiety disorder. There was some attrition at
      follow-up assessments. Results suggest that affective mechanisms may contribute
      to the high rates of co-occurrence of social anxiety and depression in both MDD
      and BD. Implications of the differential role of PA and NA in the relationship
      between social anxiety and depression in MDD and BD and considerations for
      treatment are discussed.

PMID- 29029680
TI  - Long-Term Effectiveness of Treatment-as-Usual Couple Therapy for Military
      Veterans.
AB  - Despite the fact that veterans face increased psychological and relationship
      distress as a result of their service-related experiences, no study to date has
      explored the long-term effectiveness of couple therapy for veterans. In the
      present investigation, 238 individuals (113 couples and 12 additional
      individuals) completed assessments 18 months after termination of treatment-as
      usual couple therapy at two Veteran Administration Medical Centers. From
      pretreatment to 18-month follow-up, couples experienced significant increases in
      relationship satisfaction (d = 0.59) and significant decreases in both
      psychological distress (d = -0.31) and presence of intimate partner violence (d =
      -0.47). Overall, pretreatment demographic, psychological, and relationship
      characteristics did not significantly moderate maintenance of gains across 18
      months. However, African American individuals (d = -0.58) and individuals not
      reporting intimate partner violence at pretreatment (d = -0.46) experienced
      smaller improvements in relationship satisfaction through 18-month follow-up.
      Further, older participants showed smaller reductions in psychological symptoms
      18 months after treatment (d = 0.16). Thus, for many veterans and their spouses,
      treatment-as-usual couple therapy is effective at intervening in psychological
      and relationship distress long-term. Moreover, the long-term effectiveness of
      couple therapy with veterans appears to generalize across many demographic,
      intrapersonal, and interpersonal factors.

PMID- 29029681
TI  - Does Situation-Specificity Affect the Operation of Implementation Intentions?
AB  - Interventions that encourage people to link critical situations with appropriate
      responses (i.e., "implementation intentions") show promise in increasing physical
      activity. The study tested whether implementation intentions designed to deal
      with generic situations are more effective than implementation intentions
      designed to respond to specific situations. One hundred thirty-three participants
      either: (a) formed implementation intentions using a volitional help sheet with
      10 critical situations (i.e., standard volitional help sheet); (b) formed
      implementation intentions using a volitional help sheet with one generic
      situation (i.e., single situation volitional help sheet); or (c) did not form
      implementation intentions (i.e., control condition). Participants who formed
      implementation intentions reported more physical activity and greater self
      regulation than those in the control condition. There were no differences between
      participants who were provided with one generic critical situation and those who
      were provided with 10 specific critical situations. Implementation intentions
      successfully increased self-reported physical activity irrespective of critical
      situation specificity. The implication is that implementation intention-based
      interventions are robust and require minimal tailoring.

PMID- 29029679
TI  - Investigating Habituation to Premonitory Urges in Behavior Therapy for Tic
      Disorders.
AB  - Behavior therapy is effective for Persistent Tic Disorders (PTDs), but behavioral
      processes facilitating tic reduction are not well understood. One process,
      habituation, is thought to create tic reduction through decreases in premonitory
      urge severity. The current study tested whether premonitory urges decreased in
      youth with PTDs (N = 126) and adults with PTDs (N = 122) who participated in
      parallel randomized clinical trials comparing behavior therapy to psychoeducation
      and supportive therapy (PST). Trends in premonitory urges, tic severity, and
      treatment outcome were analyzed according to the predictions of a habituation
      model, whereby urge severity would be expected to decrease in those who responded
      to behavior therapy. Although adults who responded to behavior therapy showed a
      significant trend of declining premonitory urge severity across treatment,
      results failed to demonstrate that behavior therapy specifically caused changes
      in premonitory urge severity. In addition, reductions in premonitory urge
      severity in those who responded to behavior therapy were significant greater than
      those who did not respond to behavior therapy but no different than those who
      responded or did not respond to PST. Children with PTDs failed to show any
      significant changes in premonitory urges. Reductions in premonitory urge severity
      did not mediate the relationship between treatment and outcome in either adults
      or children. These results cast doubt on the notion that habituation is the
      therapeutic process underlying the effectiveness of behavior therapy, which has
      immediate implications for the psychoeducation and therapeutic rationale
      presented in clinical practice. Moreover, there may be important developmental
      changes in premonitory urges in PTDs, and alternative models of therapeutic
      change warrant investigation.

PMID- 29029683
TI  - Corrigendum.

PMID- 29029682
TI  - A Comparison of Veterans Who Repeat Versus Who Do Not Repeat a Course of
      Manualized, Cognitive-Behavioral Therapy for Posttraumatic Stress Disorder.
AB  - Despite evidence that cognitive-behavioral therapy (CBT) for posttraumatic stress
      disorder (PTSD) is effective, some individuals do not experience clinically
      significant reduction or remission of their PTSD symptoms. These individuals may
      return for additional PTSD-focused psychotherapy. However, there is no research
      to know whether PTSD treatment repeaters have worse symptoms prior to the initial
      treatment episode or display differences in other pretreatment characteristics
      versus nonrepeaters. Research is also needed to explore whether treatment
      repeaters exhibit PTSD symptom changes during an initial or second course of
      treatment. The current study examines differences in pretreatment characteristics
      and treatment response among U.S. military veterans who participated in either a
      single course (n = 711) or in two separate courses (n = 87) of CBT for PTSD
      through an outpatient Veterans Affairs PTSD treatment program. Veterans
      completing two courses of CBT for PTSD were more likely to be married and
      employed and more likely to drop out of their initial course of treatment versus
      those who completed a single course. Hierarchical linear models showed that
      reductions in PTSD symptoms during treatment were not different for those who
      completed a second versus single course of CBT for PTSD. However, for those
      participating in two courses of CBT for PTSD, a relapse in PTSD symptoms was
      observed between the first and second course. These findings show that a second
      course of CBT may be viable for those with ongoing PTSD symptoms.

PMID- 29029684
TI  - Validation of the three web quality dimensions of a minimally invasive surgery e
      learning platform.
AB  - INTRODUCTION: E-learning web environments, including the new TELMA platform, are
      increasingly being used to provide cognitive training in minimally invasive
      surgery (MIS) to surgeons. A complete validation of this MIS e-learning platform
      has been performed to determine whether it complies with the three web quality
      dimensions: usability, content and functionality. METHODS: 21 Surgeons
      participated in the validation trials. They performed a set of tasks in the TELMA
      platform, where an e-MIS validity approach was followed. Subjective
      (questionnaires and checklists) and objective (web analytics) metrics were
      analysed to achieve the complete validation of usability, content and
      functionality. RESULTS: The TELMA platform allowed access to didactic content
      with easy and intuitive navigation. Surgeons performed all tasks with a close-to
      ideal number of clicks and amount of time. They considered the design of the
      website to be consistent (95.24%), organised (90.48%) and attractive (85.71%).
      Moreover, they gave the content a high score (4.06 out of 5) and considered it
      adequate for teaching purposes. The surgeons scored the professional language and
      content (4.35), logo (4.24) and recommendations (4.20) the highest. Regarding
      functionality, the TELMA platform received an acceptance of 95.24% for navigation
      and 90.48% for interactivity. CONCLUSIONS: According to the study, it seems that
      TELMA had an attractive design, innovative content and interactive navigation,
      which are three key features of an e-learning platform. TELMA successfully met
      the three criteria necessary for consideration as a website of quality by
      achieving more than 70% of agreements regarding all usability, content and
      functionality items validated; this constitutes a preliminary requirement for an
      effective e-learning platform. However, the content completeness, authoring tool
      and registration process required improvement. Finally, the e-MIS validity
      methodology used to measure the three dimensions of web quality in this work can
      be applied to other clinical areas or training fields.

PMID- 29029685
TI  - Using structured and unstructured data to identify patients' need for services
      that address the social determinants of health.
AB  - INTRODUCTION: Increasingly, health care providers are adopting population health
      management approaches that address the social determinants of health (SDH).
      However, effectively identifying patients needing services that address a SDH in
      primary care settings is challenging. The purpose of the current study is to
      explore how various data sources can identify adult primary care patients that
      are in need of services that address SDH. METHODS: A cross-sectional study
      described patients in need of SDH services offered by a safety-net hospital's
      federally qualified health center clinics. SDH services of social work,
      behavioral health, nutrition counseling, respiratory therapy, financial planning,
      medical-legal partnership assistance, patient navigation, and pharmacist
      consultation were offered on a co-located basis and were identified using
      structured billing and scheduling data, and unstructured electronic health record
      data. We report the prevalence of the eight different SDH service needs and the
      patient characteristics associated with service need. Moreover, characteristics
      of patients with SDH services need documented in structured data sources were
      compared with those documented by unstructured data sources. RESULTS: More than
      half (53%) of patients needed SDH services. Those in need of such services tended
      to be female, older, more medically complex, and higher utilizers of services.
      Structured and unstructured data sources exhibited poor agreement on patient SDH
      services need. Patients with SDH services need documented by unstructured data
      tended to be more complex. DISCUSSION: The need for SDH services among a safety
      net population is high. Identifying patients in need of such services requires
      multiple data sources with structured and unstructured data.

PMID- 29029686
TI  - Online written consultation, telephone consultation and offline appointment: An
      examination of the channel effect in online health communities.
AB  - INTRODUCTION: The emergence of online health communities broadens and diversifies
      channels for patient-doctor interaction. Given limited medical resources, online
      health communities aim to provide better treatment by decreasing medical costs,
      making full use of available resources and providing more diverse channels for
      patients. OBJECTIVES: This research examines how online channel usage affects
      offline channels, i.e., "Online Booking, Service in Hospitals" (OBSH), and how
      the channel effects change with doctors' online and offline reputation. METHODS:
      The study uses data of 4254 doctors from a Chinese online health community.
      RESULTS: Our findings demonstrate a strong relationship between online health
      communities and offline hospital communication with an important moderating role
      for reputation. There are significant channel effects, wherein written
      consultation complements OBSH (beta=3.320, p<0.10), but telephone consultation
      can be a readily substitute for OBSH (beta=-9.854, p<0.001). We also find that
      doctors with higher online and offline reputations can attract more patients to
      use the OBSH (betaonline=0.433, p<0.001; betaoffline=2.318&2.123, p<0.001).
      Third, channel effects fluctuate, relative to doctors' online and offline
      reputations: doctors with higher online reputations mitigate substitution effects
      between telephone consultation and OBSH (beta=0.064, p<0.01), and doctors with
      higher offline reputations mitigate complementary effects between written
      consultation and OBSH (beta=-1.586&-1.417, p<0.001). CONCLUSIONS: This study
      contributes to both knowledge and practice. This study shows that there is
      channel effect in healthcare, websites' managers can encourage physicians to
      provide online services, especially for these physicians who do not have enough
      patients.

PMID- 29029687
TI  - A qualitative study of COPD-patients' experience of a telemedicine intervention.
AB  - BACKGROUND: Clinically stable patients with chronic obstructive pulmonary disease
      (COPD) are often followed at regular intervals regardless of the needs. Our aim
      was to investigate the patient perspective on receiving telemedicine with weekly
      submission of readings and regular video consultations (Net-COPD) as an
      alternative to visits in the respiratory outpatient clinic and investigating the
      role of telemedicine in management of severe COPD. DESIGN: Descriptive design and
      the method is qualitative based on semistructured interviews. METHODS: Fourteen
      intervention patients participated from the Danish randomized clinical trial Net
      COPD project. The transcribed interviews were analysed using manifest and latent
      content analysis. FINDINGS: Participants reported that Net-COPD brought enhanced
      wellbeing and a sense of security in knowing that nurses kept an eye on them and
      initiated appropriate interventions in case of changes in the patient's
      condition. This was experienced as a lifeline to the respiratory outpatient
      clinic, which could be contacted when needed. Through monitoring, moreover,
      patients developed increased awareness and better self-management of their
      disease. Patients also experienced more focused and less stressful meetings via
      video consultations, than in respiratory outpatient visits. Nevertheless it was
      important that it was the same health staff patient met in the video
      consultations. CONCLUSION: Participation in telemedicine increased the patient
      empowerment primarily by the sharing of data with a permanent staff of nurses.
      This knowledge was used to keep control of the disease in the form of extra
      readings and the systematic use of learned initiatives. This gave patients and
      relatives a sense of security.

PMID- 29029689
TI  - Implementation of a cloud-based electronic medical record exchange system in
      compliance with the integrating healthcare enterprise's cross-enterprise document
      sharing integration profile.
AB  - In 2011, the Ministry of Health and Welfare of Taiwan established the National
      Electronic Medical Record Exchange Center (EEC) to permit the sharing of medical
      resources among hospitals. This system can presently exchange electronic medical
      records (EMRs) among hospitals, in the form of medical imaging reports,
      laboratory test reports, discharge summaries, outpatient records, and outpatient
      medication records. Hospitals can send or retrieve EMRs over the virtual private
      network by connecting to the EEC through a gateway. International standards
      should be adopted in the EEC to allow users with those standards to take
      advantage of this exchange service. In this study, a cloud-based EMR-exchange
      prototyping system was implemented on the basis of the Integrating the Healthcare
      Enterprise's Cross-Enterprise Document Sharing integration profile and the
      existing EMR exchange system. RESTful services were used to implement the
      proposed prototyping system on the Microsoft Azure cloud-computing platform. Four
      scenarios were created in Microsoft Azure to determine the feasibility and
      effectiveness of the proposed system. The experimental results demonstrated that
      the proposed system successfully completed EMR exchange under the four scenarios
      created in Microsoft Azure. Additional experiments were conducted to compare the
      efficiency of the EMR-exchanging mechanisms of the proposed system with those of
      the existing EEC system. The experimental results suggest that the proposed
      RESTful service approach is superior to the Simple Object Access Protocol method
      currently implemented in the EEC system, according to the irrespective response
      times under the four experimental scenarios.

PMID- 29029688
TI  - Subject-enabled analytics model on measurement statistics in health risk expert
      system for public health informatics.
AB  - PURPOSE: This study applied open source technology to establish a subject-enabled
      analytics model that can enhance measurement statistics of case studies with the
      public health data in cloud computing. METHODS: The infrastructure of the
      proposed model comprises three domains: 1) the health measurement data warehouse
      (HMDW) for the case study repository, 2) the self-developed modules of online
      health risk information statistics (HRIStat) for cloud computing, and 3) the
      prototype of a Web-based process automation system in statistics (PASIS) for the
      health risk assessment of case studies with subject-enabled evaluation. The
      system design employed freeware including Java applications, MySQL, and R
      packages to drive a health risk expert system (HRES). In the design, the HRIStat
      modules enforce the typical analytics methods for biomedical statistics, and the
      PASIS interfaces enable process automation of the HRES for cloud computing. The
      Web-based model supports both modes, step-by-step analysis and auto-computing
      process, respectively for preliminary evaluation and real time computation.
      RESULTS: The proposed model was evaluated by computing prior researches in
      relation to the epidemiological measurement of diseases that were caused by
      either heavy metal exposures in the environment or clinical complications in
      hospital. The simulation validity was approved by the commercial statistics
      software. The model was installed in a stand-alone computer and in a cloud-server
      workstation to verify computing performance for a data amount of more than 230K
      sets. Both setups reached efficiency of about 105 sets per second. CONCLUSIONS:
      The Web-based PASIS interface can be used for cloud computing, and the HRIStat
      module can be flexibly expanded with advanced subjects for measurement
      statistics. The analytics procedure of the HRES prototype is capable of providing
      assessment criteria prior to estimating the potential risk to public health.

PMID- 29029690
TI  - Identifying and eliminating inefficiencies in information system usage: A lean
      perspective.
AB  - OBJECTIVES: Mismatches frequently occur between information system (IS) dictated
      workflows and actual workflows of IS users. The resulting impeded workflows
      negatively influence the efficiency with which goods or services are produced and
      delivered to customers. Within a healthcare context, impeded workflows can
      additionally have a negative impact on the safety and effectiveness of care
      delivered to patients. METHODS: This study evaluates the impact of an electronic
      health record system of a large university hospital on workflows of healthcare
      professionals from a lean management waste perspective. Workflow mismatches were
      identified from direct observations and follow-up semi-structured interviews with
      physicians and nurses and assessed in terms of waste generated. RESULTS: In
      total, 241 manifestations of waste were identified and classified according to 8
      types of waste. Furthermore, noteworthy relationships among the identified
      manifestations of waste were found. These include differences in frequency per
      type of waste, certain types of waste having a cascading effect, and waste
      proliferating as a result of mimicked and routinized behavior. CONCLUSIONS: The
      knowledge obtained from this study can support (re)design of IS to better match
      workflows which may subsequently lead to more safe, effective and efficient
      patient care.

PMID- 29029691
TI  - Geo-spatial reporting for monitoring of household immunization coverage through
      mobile phones: Findings from a feasibility study.
AB  - BACKGROUND: The addition of Global Positioning System (GPS) to a mobile phone
      makes it a very powerful tool for surveillance and monitoring coverage of health
      programs. This technology enables transfer of data directly into computer
      applications and cross-references to Geographic Information Systems (GIS) maps,
      which enhances assessment of coverage and trends. OBJECTIVE: Utilization of these
      systems in low and middle income countries is currently limited, particularly for
      immunization coverage assessments and polio vaccination campaigns. We piloted the
      use of this system and discussed its potential to improve the efficiency of field
      based health providers and health managers for monitoring of the immunization
      program. METHODS: Using "30*7" WHO sampling technique, a survey of children less
      than five years of age was conducted in random clusters of Karachi, Pakistan in
      three high risk towns where a polio case was detected in 2011. Center point of
      the cluster was calculated by the application on the mobile. Data and location
      coordinates were collected through a mobile phone. This data was linked with an
      automated mHealth based monitoring system for monitoring of Supplementary
      Immunization Activities (SIAs) in Karachi. After each SIA, a visual report was
      generated according to the coordinates collected from the survey. RESULT: A total
      of 3535 participants consented to answer to a baseline survey. We found that the
      mobile phones incorporated with GIS maps can improve efficiency of health
      providers through real-time reporting and replacing paper based questionnaire for
      collection of data at household level. Visual maps generated from the data and
      geospatial analysis can also give a better assessment of the immunization
      coverage and polio vaccination campaigns. CONCLUSION: The study supports a model
      system in resource constrained settings that allows routine capture of individual
      level data through GPS enabled mobile phone providing actionable information and
      geospatial maps to local public health managers, policy makers and study staff
      monitoring immunization coverage.

PMID- 29029692
TI  - e-Health readiness assessment factors and measuring tools: A systematic review.
AB  - BACKGROUND: The evolving, adoption and high failure nature of health information
      technology (HIT)/IS/T systems requires effective readiness assessment to avert
      increasing failures while increasing system benefits. However, literature on HIT
      readiness assessment is myriad and fragmented. This review bares the contours of
      the available literature concluding in a set of manageable and usable
      recommendations for policymakers, researchers, individuals and organizations
      intending to assess readiness for any HIT implementation. OBJECTIVES: Identify
      studies, analyze readiness factors and offer recommendations. METHOD: Published
      articles 1995-2016 were searched using Medline/PubMed, Cinahl, Web of Science,
      PsychInfo, ProQuest. Studies were included if they were assessing IS/T/mHealth
      readiness in the context of HIT. Articles not written in English were excluded.
      Themes that emerged in the process of the data synthesis were thematically
      analysed and interpreted. RESULTS: Analyzed themes were found across 63 articles.
      In accordance with their prevalence of use, they included but not limited to
      "Technological readiness", 30 (46%); "Core/Need/Motivational readiness", 23
      (37%); "Acceptance and use readiness", 19 (29%); "Organizational readiness", 20
      (21%); "IT skills/Training/Learning readiness" (18%), "Engagement readiness", 16
      (24%) and "Societal readiness" (14%). Despite their prevalence in use,
      "Technological readiness", "Motivational readiness" and "Engagement readiness"
      all had myriad and unreliable measuring tools. Core readiness had relatively
      reliable measuring tools, which repeatedly been used in various readiness
      assessment studies CONCLUSION: Thus, there is the need for reliable measuring
      tools for even the most commonly used readiness assessment factors/constructs:
      Core readiness, Engagement and buy-ins readiness, Technological readiness and IT
      Skills readiness as this could serve as an immediate step in conducting
      effective/reliable e-Health readiness assessment, which could lead to reduced HIT
      implementation failures.

PMID- 29029693
TI  - What can Google and Wikipedia can tell us about a disease? Big Data trends
      analysis in Systemic Lupus Erythematosus.
AB  - OBJECTIVE: To investigate trends of Internet search volumes linked to Systemic
      Lupus Erythematosus (SLE), on-going clinical trials and research developments
      associated to the disease, using Big Data monitoring and data mining. METHODS: We
      performed a longitudinal analysis based on the large amount of data generated by
      Google Trends, scientific search tools (SCOPUS,
      Medline/Pubmed/ClinicalTrails.gov) considering 'SLE', and 'lupus' in a 5-year web
      based research. Wikipedia page views were also analysed using WikiTrends and the
      results were compared with the search volumes generated by Google Trends.
      RESULTS: We observed an overall higher distribution of search volumes from Google
      Trends in United States, South America, Canada, South Africa, Australia and
      Europe (mainly Italy, United Kingdom, Spain, France, Germany), showing a
      geographically heterogeneity in insight into health-related behaviour of the
      different populations towards SLE. By comparing the search volumes analysing the
      Wikipedia page views of both SLE and belimumab, we found a close peak trend,
      reflecting the knowledge translation after the approval of belimumab for the
      treatment of SLE. When focusing on search volumes of Google Trends, we noticed
      that the highest peaks were related to news headlines that involved celebrities
      affected by SLE, also when comparing to the peak generated by the approval of
      belimumab. CONCLUSION: This new approach, able to investigate health information
      seeking, might give an estimate of the health-related demand and even of the
      health-related behaviour of SLE, bringing new light to unanswered questions.

PMID- 29029694
TI  - Prescriber response to computerized drug alerts for electronic prescriptions
      among hospitalized patients.
AB  - BACKGROUND: Clinical decision support systems (CDSS) reduce prescription errors,
      but their effectiveness is reduced by high alert rates, "alert fatigue", and
      indiscriminate rejection. OBJECTIVES: To compare acceptance rates of alerts
      generated by the SafeRx(r) prescription CDSS among different alert types and
      departments in a tertiary care hospital, identify factors associated with alert
      acceptance, and determine whether alert overrides were justified. METHODS: In a
      retrospective study, we compared acceptance rates of all prescription alerts
      generated in 2013 in 18 departments of Israel's largest tertiary care center. In
      a prospective study in 2 internal medicine departments, we collected data on
      factors potentially associated with alert override, and an expert panel evaluated
      the justification for each overridden alert. We used multivariate analyses to
      examine the association between patient and physician-related factors and alert
      acceptance. RESULTS: In the retrospective study, of 390,841 prescriptions, 37.1%
      triggered at least one alert, 5.3% of which were accepted. Acceptance rates
      ranged from 7.9% for excessive dose alerts to 4.0% for duplicate drug and major
      drug-drug interactions alerts (p<0.001). In the prospective study, common reasons
      for alert overriding included "irrelevance to the specific condition" and
      "medication previously tolerated by the patient". Weekend shifts (incident rate
      ratio [IRR]=1.50 [95% CI, 1.01-2.22]) and a specific department (IRR=1.87 [1.23
      2.87]) were associated with higher alert acceptance, while night shift (IRR=0.47
      [0.26-0.85]) was associated with alert override. Most alert overrides (88.6%)
      were judged justified. CONCLUSIONS: The vast majority of SafeRx(r) alerts are
      overridden, and overriding is justified in most cases. Minimizing the number of
      alerts is essential to reduce the likelihood of developing "alert fatigue". Our
      findings may inform a rational, department-specific approach for alert silencing.

PMID- 29029696
TI  - Perceived critical success factors of electronic health record system
      implementation in a dental clinic context: An organisational management
      perspective.
AB  - BACKGROUND: Electronic health records (EHR) make health care more efficient. They
      improve the quality of care by making patients' medical history more accessible.
      However, little is known about the factors contributing to the successful EHR
      implementation in dental clinics. OBJECTIVES: This article aims to identify the
      perceived critical success factors of EHR system implementation in a dental
      clinic context. METHODS: We used Grounded Theory to analyse data collected in the
      context of Brunei's national EHR - the Healthcare Information and Management
      System (Bru-HIMS). Data analysis followed the stages of open, axial and selective
      coding. RESULTS: Six perceived critical success factors emerged: usability of the
      system, emergent behaviours, requirements analysis, training, change management,
      and project organisation. The study identified a mismatch between end-users and
      product owner/vendor perspectives. DISCUSSION: Workflow changes were significant
      challenges to clinicians' confident use, particularly as the system offered
      limited modularity and configurability. Recommendations are made for all the
      parties involved in healthcare information systems implementation to manage the
      change process by agreeing system goals and functionalities through wider
      consensual debate, and participated supporting strategies realised through common
      commitment.

PMID- 29029695
TI  - Continued use of an interactive computer game-based visual perception learning
      system in children with developmental delay.
AB  - This study developed an interactive computer game-based visual perception
      learning system for special education children with developmental delay. To
      investigate whether perceived interactivity affects continued use of the system,
      this study developed a theoretical model of the process in which learners decide
      whether to continue using an interactive computer game-based visual perception
      learning system. The technology acceptance model, which considers perceived ease
      of use, perceived usefulness, and perceived playfulness, was extended by
      integrating perceived interaction (i.e., learner-instructor interaction and
      learner-system interaction) and then analyzing the effects of these perceptions
      on satisfaction and continued use. Data were collected from 150 participants
      (rehabilitation therapists, medical paraprofessionals, and parents of children
      with developmental delay) recruited from a single medical center in Taiwan.
      Structural equation modeling and partial-least-squares techniques were used to
      evaluate relationships within the model. The modeling results indicated that both
      perceived ease of use and perceived usefulness were positively associated with
      both learner-instructor interaction and learner-system interaction. However,
      perceived playfulness only had a positive association with learner-system
      interaction and not with learner-instructor interaction. Moreover, satisfaction
      was positively affected by perceived ease of use, perceived usefulness, and
      perceived playfulness. Thus, satisfaction positively affects continued use of the
      system. The data obtained by this study can be applied by researchers, designers
      of computer game-based learning systems, special education workers, and medical
      professionals.

PMID- 29029697
TI  - The identification of transcriptional regulation related gene of laccase poxc
      through yeast one-hybrid screening from Pleurotus ostreatus.
AB  - Pleurotus ostreatus laccase gene poxc is transcriptionally induced by copper, and
      several putative MREs have been found and confirmed in its promoter region.
      However, the related transcription factors mediating copper response via MREs
      have not been reported. To isolate MRE binding proteins, we carried out yeast one
      hybrid screens. Reporter genes containing two trimers of the cMRE2 and cMRE3
      element were prepared and introduced into a yeast strain. The yeast was
      transformed with library cDNA that represents RNA isolated from CuSO4-treated
      fungi of P. ostreatus. From the screen of yeast transformants, we isolated ltf4
      which encoded protein with HTH DNA binding domain. Electrophoretic mobility shift
      assay suggested direct and specific interaction of ltf4 with the MRE2 of poxc.
      Quantitative RT-PCR showed that the transcription of ltf4 was significantly up
      regulated after the copper addition, and the expression trend was consistent with
      the poxc after copper introduction. The results indicated that ltf4 could
      interact with cMRE2 and thus participated in the regulation of copper mediated
      poxc transcription in P. ostreatus.

PMID- 29029698
TI  - Intrinsic disorder is a common structural characteristic of RxLR effectors in
      oomycete pathogens.
AB  - Intrinsic disorder is common in nature and has been studied to play important
      biological roles in bacterial effectors. However, disorder in oomycete RxLR
      effectors has not been investigated previously and the roles are unknown. Our
      results of PONDR VL-XT disorder analysis showed that predicted oomycete RxLR
      effectors were significantly more disordered than other effectors and secretome.
      The distribution of disorder content presented preference that RxLR-dEER regions
      were enriched in disordered residues, suggesting potential role of disorder in
      effector translocation. In contrast, the disorder content was depleted in the C
      terminal regions, especially for W/Y/L motifs. We also found that around 42 % of
      putative RxLR proteins were predicted to contain at least one alpha-helix-forming
      molecular recognition feature (alpha-MoRF), and most alpha-MoRFs were located in
      the C-terminal regions. Furthermore, both of the disorder mutants of PsAvh18 and
      PcAvh207 lost the cell death-inducing activity, indicating the potential
      important role of disordered structure in RxLR effector function. Overall, these
      results demonstrate that intrinsic disorder is a common characteristic of
      oomycete RxLR proteins, and we postulate that such structure feature may be
      important for effector translocation or function. This study extends our
      understanding of RxLR effectors in protein structures, and opens up new
      directions to explore novel mechanisms of oomycete RxLR effectors.

PMID- 29029699
TI  - Viability, purity, and genetic stability of entomopathogenic fungi species using
      different preservation methods.
AB  - Preservation methods for entomopathogenic fungi (EPF) require effective protocols
      to ensure uniform processes and to avoid alterations during storage. The aim of
      this study was to preserve Beauveria bassiana, Metarhizium acridum, M.
      anisopliae, M. rileyi, Isaria javanica, Hirsutella thompsonii, H. citriformis and
      Lecanicillium lecanii in mineral oil (MO), sterile water (SW), silica gel (SG),
      lyophilisation (L), ultracold-freezing at -70  degrees C, and cryopreservation at
      -196  degrees C. The viability and purity of the fungi were then verified:
      phenotypic characteristics were evaluated qualitatively at 6, 12 and 24 m.
      Genetic stability was tested by amplified fragment length polymorphisms (AFLP)
      analysis at 24 m. Of the eight species of EPF, three remained viable in SW, five
      in MO and L, six at -70  degrees C, seven in SG, and eight at -196  degrees C. No
      significant changes were observed in AFLP patterns at 24 m of storage. The most
      effective preservation methods for EPF were SG, L, -70 and -196  degrees C.
      Beauveria bassiana, M. acridum, M. anisopliae, M. rileyi and I. javanica remained
      stable with all methods, while the remaining species were less compatible. The
      optimisation of preservation methods for EPF facilitates the development of
      reliable protocols to ensure their inherent characteristics in culture
      collections.

PMID- 29029700
TI  - Lipid components of bile increase the protective effect of conjugated bile salts
      against antifungal drugs.
AB  - Fungi and bacteria can persist in the human gall bladder. Previous studies have
      shown that bile protects Candida albicans in this cryptic host niche from
      antifungals, providing a reservoir for intestinal re-colonization after
      discontinuation of antifungal therapy. Bile and conjugated bile salts trap
      antifungals in micelles, thereby reducing their bioavailability and possibly
      promoting the development of drug resistance. Here we show that the protective
      effect of bile and conjugated bile salts is not limited to C. albicans, but also
      observed with other fungi. Interestingly, bile, but not conjugated bile salts
      conferred resistance of C. albicans against fluconazole and only bile mediated
      resistance of Aspergillus terreus against voriconazole. To investigate this
      higher potency of bile we aimed in a step-wise reconstitution of bile from
      conjugated bile salts. Neither addition of phospholipids nor saturated fatty
      acids protected from azoles. In contrast, supplementation with polyunsaturated
      fatty acids increased azole resistance and decreased the critical micelle
      concentration of conjugated bile salts to the level of bile. Therefore,
      polyunsaturated fatty acids are vital for mixed micelle formation with high
      potential to trap antifungals. As biliary infections are difficult to treat, drug
      efficacy in the biliary system should be tested by using reconstituted synthetic
      bile.

PMID- 29029701
TI  - Out of Asia: Biogeography of fungal populations reveals Asian origin of
      diversification of the Laccaria amethystina complex, and two new species of
      violet Laccaria.
AB  - Purple Laccaria are ectomycorrhizal basidiomycetes associated with temperate
      forests all over the Northern Hemisphere in at least two taxa: Laccaria
      amethysteo-occidentalis in North America, and L. amethystina complex in Eurasia,
      as shown by Vincenot et al. (2012). Here, we combine a further study of the
      genetic structure of L. amethystina populations from Europe to southwestern China
      and Japan, using neutral Single Sequence Repeat (SSR; microsatellite) markers;
      and a systematic description of two novel Asian species, namely Laccaria
      moshuijun and Laccaria japonica, based on ecological, morphological, and
      molecular criteria (rDNA sequences). Population genetics provides evidence of the
      ancient isolation of three regional groups, with strong signal for speciation,
      and suggests a centre of origin of modern populations closest to present-day
      Chinese populations. Phylogenetic analyses confirm speciation at the molecular
      level, reflected in morphological features: L. moshuijun samples (from Yunnan,
      China) display strongly variable cheilocystidia, while L. japonica samples (from
      Japan) present distinctive globose to subglobose spores and clavate
      cheilocystidia. This study of a species complex primarily described with an
      extremely wide ecological and geographical range sheds new light on the
      biodiversity and biogeography of ectomycorrhizal fungi.

PMID- 29029702
TI  - Lysyl-tRNA synthetase (Krs) acts a virulence factor of Beauveria bassiana by its
      vital role in conidial germination and dimorphic transition.
AB  - Krs is a class II lysyl-tRNA synthetase (KRS) that is involved in cytosolic
      protein synthesis in budding yeast but functionally has not been explored in
      filamentous fungi. Previous transcriptomic analysis has revealed that a Krs
      coding gene is likely involved in pathogenesis of Beauveria bassiana, a classic
      insect pathogen as a global source of fungal insecticides. Here, we show that Krs
      is localized in the cytoplasm of hyphal cells and acts as a substantial virulence
      factor in B. bassiana. Deletion of krs resulted in 10-h delayed germination,
      decreased (15 %) thermotolerance, and lowered (46 %) UV-B resistance of aerial
      conidia despite limited impact on conidiation capacity and slight or
      inconspicuous influence on radial growth on rich and minimal media with different
      carbon (10 sugars/polyols) and nitrogen (17 amino acids) sources. The deletion
      mutant suffered 58 % reduction in submerged blastospore yield (an index of in
      vitro dimorphic transition rate) in a minimal medium, and the reduction increased
      to 71 % in another trehalose-based medium mimic to insect haemolymph. In
      standardized bioassays, median lethal actions of Deltakrs against Galleria
      mellonella larvae through the infections passing and bypassing the insect cuticle
      were prolonged to 192 and 153 h from wild-type median lethal time (LT50)
      estimates of 119 and 109 h, respectively. Microscopic examination revealed 2-d
      delayed presence of in vivo formed hyphal bodies in the haemolymph of the larvae
      infected by Deltakrs in either mode. These findings unveil a vital role of Krs in
      conidial germination and dimorphic transition and its contribution to the fungal
      potential against arthropod pests.

PMID- 29029703
TI  - Comparative genomics of maize ear rot pathogens reveals expansion of carbohydrate
      active enzymes and secondary metabolism backbone genes in Stenocarpella maydis.
AB  - Stenocarpella maydis is a plant pathogenic fungus that causes Diplodia ear rot,
      one of the most destructive diseases of maize. To date, little information is
      available regarding the molecular basis of pathogenesis in this organism, in part
      due to limited genomic resources. In this study, a 54.8 Mb draft genome assembly
      of S. maydis was obtained with Illumina and PacBio sequencing technologies, and
      analyzed. Comparative genomic analyses with the predominant maize ear rot
      pathogens Aspergillus flavus, Fusarium verticillioides, and Fusarium graminearum
      revealed an expanded set of carbohydrate-active enzymes for cellulose and
      hemicellulose degradation in S. maydis. Analyses of predicted genes involved in
      starch degradation revealed six putative alpha-amylases, four extracellular and
      two intracellular, and two putative gamma-amylases, one of which appears to have
      been acquired from bacteria via horizontal transfer. Additionally, 87 backbone
      genes involved in secondary metabolism were identified, which represents one of
      the largest known assemblages among Pezizomycotina species. Numerous secondary
      metabolite gene clusters were identified, including two clusters likely involved
      in the biosynthesis of diplodiatoxin and chaetoglobosins. The draft genome of S.
      maydis presented here will serve as a useful resource for molecular genetics,
      functional genomics, and analyses of population diversity in this organism.

PMID- 29029705
TI  - Introduction.

PMID- 29029704
TI  - Wood decay fungus Flavodon ambrosius (Basidiomycota: Polyporales) is widely
      farmed by two genera of ambrosia beetles.
AB  - The ambrosia fungus Flavodon ambrosius is the primary nutritional mutualist of
      ambrosia beetles Ambrosiodmus and Ambrosiophilus in North America. F. ambrosius
      is the only known ambrosial basidiomycete, unique in its efficient lignocellulose
      degradation. F. ambrosius is associated with both native American beetle species
      and species introduced from Asia. It remains unknown whether F. ambrosius is
      strictly a North American fungus, or whether it is also associated with these
      ambrosia beetle genera on other continents. We isolated fungi from the mycangia
      and galleries of ambrosia beetles Ambrosiodmus rubricollis, Ambrosiodmus minor,
      Ambrosiophilus atratus, and Ambrosiophilus subnepotulus in China, South Korea,
      and Vietnam. Phylogenetic analyses suggest that all Asian and North American
      isolates represent a single haplotype. These results confirm Flavodon ambrosius
      as the exclusive mutualistic fungus of multiple Ambrosiodmus and Ambrosiophilus
      beetle species around the world, making it the most widespread known ambrosia
      fungus species, both geographically and in terms of the number of beetle species.
      The Flavodon-beetle symbiosis appears to employ an unusually strict mechanism for
      maintaining fidelity, compared to the symbioses of the related Xyleborini
      beetles, which mostly vector more dynamic fungal communities.

PMID- 29029706
TI  - Pulmonary Embolism in 2017: How We Got Here and Where Are We Going?
AB  - In the 1970s, both the Urokinase Pulmonary Embolism and Urokinase-Streptokinase
      Pulmonary Embolism trials began the quest to develop thrombolytic therapy for the
      treatment of acute massive and submassive pulmonary embolism (PE). The goals of
      these studies were the immediate reduction in clot burden, restoration of
      hemodynamic stability, and improved survival. Major bleeding became the major
      barrier for clinicians to employ these therapies. From 1980s to the present time,
      a number of studies using recombinant tissue-type plasminogen activator for
      achieving these same above outcomes were completed but major bleeding continued
      to remain an adoption barrier. Finally, the concept of bringing the thrombolytic
      agent into the clot has entered the quest for the Holy Grail in the treatment of
      PE. This article will review all the major trials using peripheral thrombolysis
      and provide insight into the need for a team approach to pulmonary care
      (Pulmonary Embolism Response Team), standardization of pulmonary classification,
      and the need for trials designed for both short- and long-term outcomes using
      thrombolysis for selected PE populations.

PMID- 29029707
TI  - Epidemiology, Pathophysiology, Stratification, and Natural History of Pulmonary
      Embolism.
AB  - Pulmonary embolism (PE) is a common and potentially fatal form of venous
      thromboembolism that can be challenging to diagnose and manage. PE occurs when
      there is obstruction of the pulmonary vasculature and is a common cause of
      morbidity and mortality in the United States. A combination of acquired and
      inherited factors may contribute to the development of this disease and should be
      considered, since they have implications for both susceptibility to PE and
      treatment. Patients with suspected PE should be evaluated efficiently to diagnose
      and administer therapy as soon as possible, but the presentation of PE is
      variable and nonspecific so diagnosis is challenging. PE can range from small,
      asymptomatic blood clots to large emboli that can occlude the pulmonary arteries
      causing sudden cardiovascular collapse and death. Thus, risk stratification is
      critical to both the prognosis and management of acute PE. In this review, we
      discuss the epidemiology, risk factors, pathophysiology, and natural history of
      PE and deep vein thrombosis.

PMID- 29029708
TI  - Anticoagulation in Pulmonary Embolism: Update in the Age of Direct Oral
      Anticoagulants.
AB  - The emergence of direct oral anticoagulants (DOACs) represents a major
      advancement and paradigm shift in the treatment of venous thromboembolism.
      Currently, dabigatran, rivaroxaban, apixiban, and edoxoban are approved and used
      routinely for the prevention and treatment of patients with venous
      thromboembolism. Because each of the DOACs has different doses and dosing
      regimens, clinicians need to become familiar with their use. This article focuses
      on the practical considerations of how and when to use the DOACs. It also aims to
      explore follow-up monitoring, use in special populations, reversal agents,
      periprocedural management, and how to handle bleeding complications with the
      DOACs.

PMID- 29029709
TI  - Medical Management of Pulmonary Embolism: Beyond Anticoagulation.
AB  - Pulmonary embolism (PE) is a common medical condition that carries significant
      morbidity and mortality. Although diagnosis, anticoagulation, and interventional
      clot-burden reduction strategies represent the focus of clinical research and
      care in PE, appropriate risk stratification and supportive care are crucial to
      ensure good outcomes. In this chapter, we will discuss the medical management of
      PE from the time of presentation to discharge, focusing on the critical care of
      acute right ventricular failure, anticoagulation of special patient populations,
      and appropriate follow-up testing after acute PE.

PMID- 29029710
TI  - Systemic Thrombolysis for Pulmonary Embolism: Who and How.
AB  - Anticoagulation has been shown to improve mortality in acute pulmonary embolism
      (PE). Initiation of anticoagulation should be considered when PE is strongly
      suspected and the bleeding risk is perceived to be low, even if acute PE has not
      yet been proven. Low-risk patients with acute PE are simply continued on
      anticoagulation. Severely ill patients with high-risk (massive) PE require
      aggressive therapy, and if the bleeding risk is acceptable, systemic thrombolysis
      should be considered. However, despite clear evidence that parenteral
      thrombolytic therapy leads to more rapid clot resolution than anticoagulation
      alone, the risk of major bleeding including intracranial bleeding is
      significantly higher when systemic thrombolytic therapy is administered. It has
      been demonstrated that right ventricular dysfunction, as well as abnormal
      biomarkers (troponin and brain natriuretic peptide) are associated with increased
      mortality in acute PE. In spite of this, intermediate-risk (submassive) PE
      comprises a fairly broad clinical spectrum. For several decades, clinicians and
      clinical trialists have worked toward a more aggressive, yet safe solution for
      patients with intermediate-risk PE. Standard-dose thrombolysis, low-dose systemic
      thrombolysis, and catheter-based therapy which includes a number of devices and
      techniques, with or without low-dose thrombolytic therapy, have offered potential
      solutions and this area has continued to evolve. On the basis of heterogeneity
      within the category of intermediate-risk as well as within the high-risk group of
      patients, we will focus on the use of systemic thrombolysis in carefully selected
      high- and intermediate-risk patients. In certain circumstances when the need for
      aggressive therapy is urgent and the bleeding risk is acceptable, this is an
      appropriate approach, and often the best one.

PMID- 29029711
TI  - Surgical Embolectomy for Massive and Submassive Pulmonary Embolism and Pulmonary
      Thromboendarterectomy for Chronic Thromboembolic Pulmonary Hypertension.
AB  - Surgical therapy for massive acute pulmonary embolism has improved with the use
      of rapid response teams and selective bedside extracorporeal membrane oxygenation
      initiation. The chronic consequence of unresolved pulmonary embolism is a
      treatable form of pulmonary hypertension. Pulmonary thromboendarterectomy is a
      curative operation in selected cases, operated upon in an experienced center with
      the multidisciplinary team including imaging, pulmonary medicine, and
      cardiothoracic surgery.

PMID- 29029712
TI  - Advanced Cardiopulmonary Support for Pulmonary Embolism.
AB  - Management of high-risk pulmonary embolism (PE) requires an understanding of the
      pathophysiology of PE, options for rapid clot reduction, critical care
      interventions, and advanced cardiopulmonary support. PE can lead to rapid
      respiratory and hemodynamic collapse via a complex sequence of events leading to
      acute right ventricular failure. Importantly, reduction in pulmonary vascular
      resistance must be accomplished either by systemic thrombolytics, catheter
      directed thrombolytics, endovascular clot extraction, or surgical embolectomy.
      There are important advances in these techniques all of which have a niche role
      in the cardiopulmonary stabilization of critically ill patient with PE. Critical
      care support surrounding the above interventions is necessary. Maintenance of
      systemic perfusion and cardiac output may require careful titration of
      vasopressors, inotropes, and preload. Extreme caution should be taken with
      approach to intubation and positive pressure ventilation. A hemodynamically
      neutral induction with preparations for circulatory collapse should be the goal.
      Once intubated, the effect of positive pressure on pulmonary vascular resistance
      and right ventricular hemodynamics is necessary. Veno-arterial extra corporeal
      membrane oxygenation plays an increasingly important role in the stabilization of
      the hemodynamically collapsed patient who either has a contraindication to
      systemic lytics, failed systemic lytics, or requires a bridge to surgical or
      catheter embolectomy. Veno-arterial extra corporeal membrane oxygenation has also
      been used alone to stabilize the circulation until hemodynamics normalize on
      anticoagulation and has also been used in tenuous patient as a safety net for
      endovascular procedures.

PMID- 29029714
TI  - Catheter-Directed Therapy for Acute Submassive Pulmonary Embolism: Summary of
      Current Evidence and Protocols.
AB  - Treatment of acute submassive pulmonary embolism (PE) with thrombolytic therapy
      remains an area of controversy. For patients who fail or who have
      contraindications to systemic thrombolysis, catheter-directed therapy (CDT) may
      be offered depending on the patient's condition and the available institutional
      resources to perform CDT. Although various CDT techniques and protocols exist,
      the most studied method is low-dose catheter-directed thrombolytic infusion
      without mechanical thrombectomy. This article reviews current protocols and data
      on the use of CDT for acute submassive pulmonary embolism.

PMID- 29029713
TI  - Techniques and Devices for Catheter-Directed Therapy in Pulmonary Embolism.
AB  - The clinical presentation of a patient with acute pulmonary embolism (PE) can be
      classified into 3 categories: low-risk, submassive (presence of right heart
      strain), and massive (hemodynamic compromise). Massive PE is associated with high
      morbidity or mortality and typically treated with systemic intravenous
      thrombolysis. Over the last 2 decades, however, catheter-directed techniques have
      become an increasingly popular treatment modality for patients with a
      contraindication to systemic thrombolysis or without clinical improvement after
      systemic thrombolysis. Furthermore, endovascular treatment for patients with
      submassive PE has been of great interest due to the significantly increased
      mortality associated with right heart strain, and prospective clinical trials
      have demonstrated catheter-directed thrombolysis to decrease right heart strain
      earlier than systemic anticoagulation alone. This article describes available
      devices and endovascular techniques used to treat patients with massive and
      submassive acute PE.

PMID- 29029715
TI  - The Role of Inferior Vena Cava Filters in Pulmonary Embolism.
AB  - Pulmonary embolism (PE) is a cause of significant morbidity and mortality, with
      an estimated 600,000 cases of clinically significant PE in the United States
      annually, and roughly 200,000 deaths per annum directly attributable to PE. By
      far the most frequent cause of PE is deep vein thrombosis originating in the
      lower extremities, which travels to the pulmonary vasculature. The mainstay of
      treatment is anticoagulation, but multiple additional treatments exist for
      patients in whom anticoagulation is inadequate or contraindicated. The absolute
      indications for inferior vena cava (IVC) filtration are narrow, but many filters
      are placed in patients with relative indications. There is growing concern for
      overuse of IVC filters, with a relatively low rate of retrieval. It is essential
      for interventional radiologists to understand the appropriate and correct use and
      retrieval of IVC filters. Familiarity with placement techniques, protocols and
      techniques for retrieval, current and emerging technologies, and the clinical
      model for management of venous thromboembolism, will ensure that interventional
      radiologists remain an integral member of the care team for these often complex
      patients.

PMID- 29029716
TI  - Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Hypertension:
      New Horizons in the Interventional Management of Pulmonary Embolism.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed
      potential complication of acute or recurrent pulmonary thromboembolic disease.
      Multiple studies suggest that up to 5% of patients with acute pulmonary
      thromboembolic disease go on to develop CTEPH. The prognosis of untreated CTEPH
      is poor, but advances in medical and surgical treatments over the past few
      decades have improved patient outcomes. The gold standard and curative treatment
      for CTEPH is pulmonary endarterectomy; however, some patients are inoperable and
      others who have undergone pulmonary endarterectomy experience persistent or
      recurrent pulmonary hypertension despite medical therapy. In recent years,
      balloon pulmonary angioplasty has emerged as a primary and adjunctive treatment
      for these CTEPH patients at expert or specialized centers. This review outlines
      an approach to balloon pulmonary angioplasty for CTEPH, including clinical
      presentation and evaluation; patient selection and indications; treatment
      planning; equipment and technique; overcoming technical challenges; recognition
      and management of complications; postprocedural care and clinical follow-up; and
      expected outcomes.

PMID- 29029717
TI  - The Role of the Pulmonary Embolism Response Team: How to Build One, Who to
      Include, Scenarios, Organization, and Algorithms.
AB  - Pulmonary embolism response teams (PERTs) are multidisciplinary response teams
      aimed at delivering a range of diagnostic and therapeutic modalities to patients
      with pulmonary embolism. These teams have gained traction on a national scale.
      However, despite sharing a common goal, individual PERT programs are quite
      individualized-varying in their methods of operation, team structures, and
      practice patterns. The tendency of such response teams is to become intensely
      structured, algorithmic, and inflexible. However, in their current form, PERT
      programs are quite the opposite. They are being creatively customized to meet the
      needs of the individual institution based on available resources, skills,
      personnel, and institutional goals. After a review of the essential core elements
      needed to create and operate a PERT team in any form, this article will discuss
      the more flexible feature development of the nascent PERT team. These include
      team planning, member composition, operational structure, benchmarking, market
      analysis, and rudimentary financial operations.

PMID- 29029718
TI  - The Future of Catheter-Directed Therapy: Data Gaps, Unmet Needs, and Future
      Trials.
AB  - This article will focus on 3 avenues for future research: (1) addressing the lack
      of short- and long-term clinical outcome research on catheter-directed therapy;
      (2) determining the safety and efficacy of novel thrombus removal devices; and
      (3) translating our knowledge of the pathobiology and pathophysiology of
      pulmonary embolism into novel diagnostic and therapeutic strategies.

PMID- 29029719
TI  - Erratum to "Not just guess work: Tips for observation, brainstorming, and
      prototyping." Vasc Interv Radiol 20 (2017) 94-100.

PMID- 29029720
TI  - Corrigendum to "Associations of herd-level housing, management, and lameness
      prevalence with productivity and cow behavior in herds with automated milking
      systems" (J. Dairy Sci. 99:9069-9079).

PMID- 29029721
TI  - Corrigendum to "A survey of dairy calf management practices among farms using
      manual and automated milk feeding systems in Canada" (J. Dairy Sci. 100:6872
      6884).

PMID- 29029722
TI  - The First "Virus Hunters".
AB  - The history of virology is a history of conceptual and technological inventions
      and breakthroughs. The development of filters made of porcelain or kieselgur by
      the end of the 19th century which withheld bacteria allowed the identification of
      infectious agents smaller than bacteria and noncultivable on the media known at
      that time and used to grow bacteria. Even finer-grain filters resulted in the
      observation that the ultravisible novel infectious agents are in fact of
      particulate nature. Infections of plants and animals were the first to be
      attributed to these tiny entities. Proof resulted from experimental infection of
      the natural hosts (including humans). Thus, of the first 30 viruses identified,
      20 are veterinary viruses, i.e. infectious agents of poultry and livestock. The
      discovery that bacteria also have viruses in the 1910s expanded the viral
      universe which continues today. Filterability and ultravisibility remained a
      hallmark for the identification of viruses until the advent of the electron
      microscope in the late 1930s marking another technological breakthrough in
      virology. Cell culture techniques allowed virus propagation outside the infected
      organism. In the past decades, the advent and development of molecular biology
      has brought more innovations culminating in the rapid and accurate determination
      of genomic material of a variety of living beings including viruses in a hitherto
      unknown speed and depth using next-generation sequencing and metagenomic
      analyses. Thus, it is no surprise that new viruses are detected constantly
      including specimens of unprecedented size and shape. Virologists agree that the
      viral universe is immense, and only a small fraction has been explored yet.

PMID- 29029723
TI  - The Expanding Field of Mammalian Astroviruses: Opportunities and Challenges in
      Clinical Virology.
AB  - Astroviruses are best known as being one of the leading causes of diarrhea in
      infants and were first described in this context in 1975. In its first years,
      astrovirus research was mainly restricted to electron microscopy and serology
      studies. The ability to culture some of these viruses in vitro allowed a first
      consequent step forward, especially at the molecular level. Since the emergence
      of more powerful genetic methods, though, the face of this research field has
      dramatically changed and evolved. From the exponential number of discoveries of
      new astrovirus strains in the most varied of animal species to their association
      with atypical diseases, these viruses revealed a lot of surprises, and many more
      are probably still waiting to be uncovered. This chapter summarizes the most
      important knowledge about astroviruses and discusses the implication of the
      latest findings in this area of research.

PMID- 29029724
TI  - New Leaves in the Growing Tree of Pestiviruses.
AB  - Pestiviruses are a group of viruses of veterinary importance infecting livestock
      animals like pigs, cattle, and sheep, and also wildlife animals like wild boar
      and different deer species. While for decades only four classical species
      (Classical swine fever virus, Bovine viral diarrhea virus types 1 and 2, Border
      disease virus), and a few so-called atypical pestiviruses were known (e.g.,
      Giraffe virus, Pronghorn virus, HoBi virus), a series of novel pestiviruses was
      identified in the last years (Bungowannah virus, Bat pestivirus, Norway rat
      pestivirus, Atypical porcine pestivirus, LINDA virus). The Australian Bungowannah
      virus could be isolated and further characterized by classical sequencing, but
      all the other latest novel pestiviruses were identified by metagenomics using
      next-generation sequencing technologies. Here, we describe these new viruses and
      their discovery and characterization. Differentiation is made between the
      occurrence of classical pestiviruses in new species and novel viruses or virus
      types.

PMID- 29029725
TI  - Bluetongue Virus: From BTV-1 to BTV-27.
AB  - Bluetongue virus (BTV) is the type species of genus Orbivirus within family
      Reoviridae. Bluetongue virus is transmitted between its ruminant hosts by the
      bite of Culicoides spp. midges. Severe BT cases are characterized by symptoms
      including hemorrhagic fever, particularly in sheep, loss of productivity, and
      death. To date, 27 BTV serotypes have been documented. These include novel
      isolates of atypical BTV, which have been almost fully characterized using deep
      sequencing technologies and do not rely on Culicoides vectors for their
      transmission among hosts. Due to its high economic impact, BT is an Office
      International des Epizooties (OIE) listed disease that is strictly controlled in
      international commercial exchanges. During the 20th century, BTV has been endemic
      in subtropical regions. In the last 15 years, novel strains of nine "typical" BTV
      serotypes (1, 2, 4, 6, 8, 9, 11, 14, and 16) invaded Europe, some of which caused
      disease in naive sheep and unexpectedly in bovine herds (particularly serotype
      8). Over the past few years, three novel "atypical" serotypes (25-27) were
      characterized during sequencing studies of animal samples from Switzerland,
      Kuwait, and France, respectively. Classical serotype-specific inactivated
      vaccines, although expensive, were very successful in controlling outbreaks as
      shown with the northern European BTV-8 outbreak which started in the summer of
      2006. Technological jumps in deep sequencing methodologies made rapid full
      characterizations of BTV genome from isolates/tissues feasible. Next-generation
      sequencing (NGS) approaches are powerful tools to study the variability of BTV
      genomes on a fine scale. This paper provides information on how NGS impacted our
      knowledge of the BTV genome.

PMID- 29029726
TI  - Loeffler 4.0: Diagnostic Metagenomics.
AB  - A new world of possibilities for "virus discovery" was opened up with high
      throughput sequencing becoming available in the last decade. While scientifically
      metagenomic analysis was established before the start of the era of high
      throughput sequencing, the availability of the first second-generation sequencers
      was the kick-off for diagnosticians to use sequencing for the detection of novel
      pathogens. Today, diagnostic metagenomics is becoming the standard procedure for
      the detection and genetic characterization of new viruses or novel virus
      variants. Here, we provide an overview about technical considerations of high
      throughput sequencing-based diagnostic metagenomics together with selected
      examples of "virus discovery" for animal diseases or zoonoses and metagenomics
      for food safety or basic veterinary research.

PMID- 29029727
TI  - The Recently Discovered Bokeloh Bat Lyssavirus: Insights Into Its Genetic
      Heterogeneity and Spatial Distribution in Europe and the Population Genetics of
      Its Primary Host.
AB  - In 2010, a novel lyssavirus named Bokeloh bat lyssavirus (BBLV) was isolated from
      a Natterer's bat (Myotis nattereri) in Germany. Two further viruses were isolated
      in the same country and in France in recent years, all from the same bat species
      and all found in moribund or dead bats. Here we report the description and the
      full-length genome sequence of five additional BBLV isolates from Germany (n=4)
      and France (n=1). Interestingly, all of them were isolated from the Natterer's
      bat, except one from Germany, which was found in a common Pipistrelle bat
      (Pipistrellus pipistrellus), a widespread and abundant bat species in Europe. The
      latter represents the first case of transmission of BBLV to another bat species.
      Phylogenetic analysis clearly demonstrated the presence of two different lineages
      among this lyssavirus species: lineages A and B. The spatial distribution of
      these two lineages remains puzzling, as both of them comprised isolates from
      France and Germany; although clustering of isolates was observed on a regional
      scale, especially in Germany. Phylogenetic analysis based on the mitochondrial
      cytochrome b (CYTB) gene from positive Natterer's bat did not suggest a
      circulation of the respective BBLV sublineages in specific Natterer's bat
      subspecies, as all of them were shown to belong to the M. nattereri sensu stricto
      clade/subspecies and were closely related (German and French positive bats). At
      the bat host level, we demonstrated that the distribution of BBLV at the late
      stage of the disease seems large and massive, as viral RNA was detected in many
      different organs.

PMID- 29029728
TI  - Software Dedicated to Virus Sequence Analysis "Bioinformatics Goes Viral".
AB  - Computer-assisted technologies of the genomic structure, biological function, and
      evolution of viruses remain a largely neglected area of research. The attention
      of bioinformaticians to this challenging field is currently unsatisfying in
      respect to its medical and biological importance. The power of new genome
      sequencing technologies, associated with new tools to handle "big data", provides
      unprecedented opportunities to address fundamental questions in virology. Here,
      we present an overview of the current technologies, challenges, and advantages of
      Next-Generation Sequencing (NGS) in relation to the field of virology. We present
      how viral sequences can be detected de novo out of current short-read NGS data.
      Furthermore, we discuss the challenges and applications of viral quasispecies and
      how secondary structures, commonly shaped by RNA viruses, can be computationally
      predicted. The phylogenetic analysis of viruses, as another ubiquitous field in
      virology, forms an essential element of describing viral epidemics and challenges
      current algorithms. Recently, the first specialized virus-bioinformatic
      organizations have been established. We need to bring together virologists and
      bioinformaticians and provide a platform for the implementation of
      interdisciplinary collaborative projects at local and international scales. Above
      all, there is an urgent need for dedicated software tools to tackle various
      challenges in virology.

PMID- 29029729
TI  - Schmallenberg Virus: A Novel Virus of Veterinary Importance.
AB  - In late 2011, unspecific clinical symptoms such as fever, diarrhea, and decreased
      milk production were observed in dairy cattle in the Dutch/German border region.
      After exclusion of classical endemic and emerging viruses by targeted diagnostic
      systems, blood samples from acutely diseased cows were subjected to metagenomics
      analysis. An insect-transmitted orthobunyavirus of the Simbu serogroup was
      identified as the causative agent and named Schmallenberg virus (SBV). It was one
      of the first detections of the introduction of a novel virus of veterinary
      importance to Europe using the new technology of next-generation sequencing. The
      virus was subsequently isolated from identical samples as used for metagenomics
      analysis in insect and mammalian cell lines and disease symptoms were reproduced
      in calves experimentally infected with both, this culture-grown virus and blood
      samples of diseased cattle. Since its emergence, SBV spread very rapidly
      throughout the European ruminant population causing mild unspecific disease in
      adult animals, but also premature birth or stillbirth and severe fetal
      malformation when naive dams were infected during a critical phase of gestation.
      In the following years, SBV recirculated regularly to a larger extend; in the
      2014 and 2016 vector seasons the virus was again repeatedly detected in the blood
      of adult ruminants, and in the following winter and spring months, a number of
      malformed calves and lambs was born. The genome of viruses present in viremic
      adult animals showed a very high sequence stability; in sequences generated
      between 2012 and 2016, only a few amino acid substitutions in comparison to the
      initial SBV isolate could be detected. In contrast, a high sequence variability
      was identified in the aminoterminal part of the glycoprotein Gc-encoding region
      of viruses present in the brain of malformed newborns. This mutation hotspot is
      independent of the region or host species from which the samples originated and
      is potentially involved in immune evasion mechanisms.

PMID- 29029730
TI  - Assessing the Diversity of Rodent-Borne Viruses: Exploring of High-Throughput
      Sequencing and Classical Amplification/Sequencing Approaches.
AB  - Rodents are distributed throughout the world and interact with humans in many
      ways. They provide vital ecosystem services, some species are useful models in
      biomedical research and some are held as pet animals. However, many rodent
      species can have adverse effects such as damage to crops and stored produce, and
      they are of health concern because of the transmission of pathogens to humans and
      livestock. The first rodent viruses were discovered by isolation approaches and
      resulted in break-through knowledge in immunology, molecular and cell biology,
      and cancer research. In addition to rodent-specific viruses, rodent-borne viruses
      are causing a large number of zoonotic diseases. Most prominent examples are
      reemerging outbreaks of human hemorrhagic fever disease cases caused by arena-
      and hantaviruses. In addition, rodents are reservoirs for vector-borne pathogens,
      such as tick-borne encephalitis virus and Borrelia spp., and may carry human
      pathogenic agents, but likely are not involved in their transmission to human. In
      our days, next-generation sequencing or high-throughput sequencing (HTS) is
      revolutionizing the speed of the discovery of novel viruses, but other molecular
      approaches, such as generic RT-PCR/PCR and rolling circle amplification
      techniques, contribute significantly to the rapidly ongoing process. However, the
      current knowledge still represents only the tip of the iceberg, when comparing
      the known human viruses to those known for rodents, the mammalian taxon with the
      largest species number. The diagnostic potential of HTS-based metagenomic
      approaches is illustrated by their use in the discovery and complete genome
      determination of novel borna- and adenoviruses as causative disease agents in
      squirrels. In conclusion, HTS, in combination with conventional RT-PCR/PCR-based
      approaches, resulted in a drastically increased knowledge of the diversity of
      rodent viruses. Future improvements of the used workflows, including
      bioinformatics analysis, will further enhance our knowledge and preparedness in
      case of the emergence of novel viruses. Classical virological and additional
      molecular approaches are needed for genome annotation and functional
      characterization of novel viruses, discovered by these technologies, and
      evaluation of their zoonotic potential.

PMID- 29029731
TI  - Dual-target inhibitor screening against thrombin and factor Xa simultaneously by
      mass spectrometry.
AB  - An accurate, rapid, and cost-effective methodology for enzyme assay is highly
      demanded to screen the effect of compounds on target at the molecular level.
      Thrombin (EC 3.4.21.5) and factor Xa (FXa, EC 3.4.21.6) have been identified as
      the critical targets for the development of potential drugs with anticoagulant
      activity. In this study, a rapid, sensitive and accurate assay based on UHPLC
      MS/MS method has been developed for inhibitor screening against thrombin and
      factor Xa simultaneously. For thrombin and factor Xa, the Michaelis-Menten
      constants (Km) were calculated to be 6.14 and 57.27 MUM, respectively. The
      inhibition constants (Ki) for two known inhibitors, argatroban and rivaroxaban,
      were determined to be 16.23 and 0.41 nM, respectively. The assay was further
      validated through the determination of a high Z' factor value of 0.89. Finally,
      the developed assay was applied to screen a chemical library against two enzymes.
      Three hit compounds belonging to a class of sulfated polysaccharides were
      identified and their targets of inhibition action were further evaluated. The
      results indicated that the dual-target assay by UHPLC-MS/MS analysis could be
      used as a reliable method for screening anticoagulant agents.

PMID- 29029732
TI  - Determination of cyanocobalamin by isotope dilution LC-MS/MS.
AB  - Cyanocobalamin (CNCbl) is an active form of vitamin B12, commonly employed for
      the preparation of multivitamin supplements and fortified food. In this study, we
      present a novel analytical method for its determination based on stable isotope
      dilution liquid chromatography electrospray tandem mass spectrometry (ID LC
      MS/MS). Isotopically enriched 13C15NCbl was synthesized in-house and used as
      internal standard. The method was validated using NIST SRM 3280 multivitamin
      reference material and by comparison with an independent methodology based on LC
      ICPMS. The proposed method provided a detection limit of 57 pg/g and could be
      applied for the determination of trace level of CNCbl in multivitamin supplements
      with a relative standard uncertainty better than 3%. The novel ID LC-MS/MS is a
      primary ratio method that could become a reference for CNCbl determination in
      multivitamins and food supplements. The method was applied for the
      characterization of two NRC multivitamin tablet Certified Reference Material
      (CRM) candidates, VITA-1 and VITB-1 whose CNCbl levels were quantified as 2.64 +/
      0.09 and 1.75 +/- 0.12 MUg/g, respectively.

PMID- 29029733
TI  - Voltammetric determination of metal ions beyond mercury electrodes. A review.
AB  - For a long time mercury electrodes have been the main choice for the analysis of
      metal ions and some metalloids. However, in the last years, safety and
      environmental considerations have restricted their use and encouraged the search
      for alternative materials more environmentally friendly and with more
      possibilities for in-situ and flow analysis. This research has been reinforced by
      the popularisation of nanomaterials, biomolecules and screen-printed electrodes,
      as well as for the new advances in sensor miniaturization and integration of the
      electrodes in multi-sensor platforms and electronic tongues. The present review
      critically summarizes and discusses the progress made since 2010 in the
      development and application of new electrodes for the analysis of metals and
      metalloids.

PMID- 29029734
TI  - 3D lung spheroid cultures for evaluation of photodynamic therapy (PDT) procedures
      in microfluidic Lab-on-a-Chip system.
AB  - The purpose of this paper is to present a fully integrated microchip for the
      evaluation of PDT procedures efficiency on 3D lung spheroid cultures. Human lung
      carcinoma A549 and non-malignant MRC-5 spheroids were utilized as culture models.
      Spheroid viability was evaluated 24 h after PDT treatment, in which 5
      aminolevulinic acid (ALA) had been used as a precursor of a photosensitizer
      (protoporphyrin IX - PpIX). Moreover, spheroid viability over a long-term (10
      day) culture was also examined. We showed that the proposed PDT treatment was
      toxic only for cancer spheroids. This could be because of a much-favoured
      enzymatic conversion of ALA to PpIX in cancer as opposed normal cells. Moreover,
      we showed that to obtain high effectiveness of ALA-PDT on lung cancer spheroids
      additional time of spheroid after light exposure was required. It was found that
      PDT had been effective 5 days after PDT treatment with 3 mM ALA. To the best of
      our knowledge this has been the first presentation of such research performed on
      a 3D lung spheroids culture in a microfluidic system.

PMID- 29029735
TI  - Reduction of production rate in Y-shaped microreactors in the presence of
      viscoelasticity.
AB  - The viscoelasticity effects on the reaction-diffusion rates in a Y-shaped
      microreactor are studied utilizing the PTT rheological model. The flow is assumed
      to be fully developed and considered to be created under a combined action of
      electroosmotic and pressure forces. In general, finite-volume-based numerical
      simulations are conducted to handle the problem; however, analytical solutions
      based on the depthwise averaging approach are also obtained for the case for
      which there is no reaction between the inlet components. The analytical solutions
      are found to predict accurate results when the width to height ratio is at least
      10 and acceptable results for lower aspect ratios. An investigation of the
      viscoelasticity effect reveals that it is accompanied by a significant reduction
      of the production rate and the production efficiency, defined as the ratio of the
      average product concentration to the inlet concentration of the limiting
      reactant. In addition, this effect gives rise to a more uniform transport with
      more symmetric concentration distributions. The pressure effects on the reaction
      diffusion rates are also pronounced in the presence of viscoelasticity. Finally,
      the influences of the product diffusivity are investigated for the first time
      revealing that the lower it is the thinner the area of significant production
      becomes.

PMID- 29029736
TI  - Rapid visual and spectrophotometric nitrite detection by cyclometalated ruthenium
      complex.
AB  - Quantitative determination of nitrite ion (NO2-) is of great importance in
      environmental and clinical investigations. A rapid visual and spectrophotometric
      assay for NO2- detection was developed based on a newly designed ruthenium
      complex, [Ru(npy)([9]aneS3)(CO)](ClO4) (denoted as RuNPY; npy = 2-(1
      naphthyl)pyridine, [9]aneS3 = 1,4,7-trithiacyclononane). This complex traps NO+
      produced in acidified NO2- solution, and yields observable color change within 1
      min at room temperature. The assay features excellent dynamic range (1-840 MUmol
      L-1) and high selectivity, and its limit of detection (0.39 MUmol L-1) is also
      well below the guideline values for drinking water recommended by WHO and U.S.
      EPA. Practical use of this assay in tap water and human urine was successfully
      demonstrated. Overall, the rapidity and selectivity of this assay overcome the
      problems suffered by the commonly used modified Griess assays for nitrite
      determination.

PMID- 29029737
TI  - Surface enhanced infrared absorption spectroscopy based on gold nanostars and
      spherical nanoparticles.
AB  - Plasmonic anisotropic nanoparticles possess a number of hot spots on their
      surface due to the presence of sharp edges, tips or vertices, leading to a high
      electric field strength surrounding the nanostructures. In this paper, we explore
      different plasmonic nanostructures, including anisotropic gold nanostars (AuNSts)
      and spherical gold nanoparticles, in surface-enhanced infrared absorption
      spectroscopy (SEIRAS) in an attenuated total reflection (ATR) configuration. In
      our experiments, we observed up to 10-times enhancement of the infrared (IR)
      absorption of thioglycolic acid (TGA) and up to 2-times enhancement of signals
      for bovine serum albumin (BSA) protein on plasmonic nanostructure-based films
      deposited on a silicon (Si) internal reflection element (IRE) compared to bare Si
      IRE. The dependence of the observed enhancement on the amount of AuNSts present
      at the surface of the IRE has been demonstrated. Quantitative studies with both,
      TGA and BSA were performed, observing that the SEIRA signal can be correlated to
      the concentration of analyte molecules present within the evanescent field. The
      calibration curves in the presence of the AuNSts showed enhanced sensitivity as
      compared with the bare Si IRE. We finally compare efficiencies of anisotropic
      AuNSts and spherical citrate-capped and "bare" laser-synthesized gold
      nanoparticles as SEIRAS substrates for the detection of TGA and BSA. The signal
      obtained from AuNSts was at least 2 times higher for TGA molecules in comparison
      with spherical gold nanoparticles, which was explained by a more efficient
      generation of hot spots on anisotropic surface due to the presence of sharp
      edges, tips or vertices, leading to a high electric field strength surrounding
      the AuNSts.

PMID- 29029738
TI  - A redox-modulated fluorescent strategy for the highly sensitive detection of
      metabolites by using graphene quantum dots.
AB  - In this paper, a redox-modulated fluorescent strategy based on the transformation
      of Fe2+/Fe3+ couple and enzymatic reaction for rapid monitoring glucose and uric
      acid using graphene quantum dots (GQDs) as fluorescent probe was developed.
      Hydrogen peroxide (H2O2) can be produced by the enzymatic reaction of a series of
      metabolites, such as glucose and uric acid. In the presence of hydrogen peroxide,
      Fe2+ can be oxidized and converted to Fe3+, which have a significant quenching
      difference in the fluorescence of graphene quantum dots (GQDs). Thus, a sensitive
      and label-free biosensor for the detection of uric acid and glucose was
      developed. Under the optimized experimental conditions, the fluorescence
      intensity was linearly correlated with the concentration of uric acid and glucose
      in the range of 0.1-45 MUmolL-1 and 0.1-30 MUmolL-1 with a detection limit of
      0.026 MUmolL-1and 0.021 MUmolL-1, respectively. The proposed method was applied
      to the determination of uric acid and glucose in human serum samples with
      satisfactory results, which had potential application to detect metabolites
      associated with H2O2 release.

PMID- 29029739
TI  - Studying the influence of stem composition in pH-sensitive molecular beacons onto
      their sensing properties.
AB  - Intracellular sensing using fluorescent molecular beacons is a potentially useful
      strategy for real-time, in vivo monitoring of important cellular events. This
      work is focused on evaluation of pyrene excimer signaling molecular beacons (MBs)
      for the monitoring of pH changes in vitro as well as inside living cells. The
      recognition element in our MB called pHSO (pH-sensitive oligonucleotide) is the
      loop enclosing cytosine-rich fragment that is able to form i-motif structure in a
      specific pH range. However, alteration of a sequence of the 6 base pairs
      containing stem of MB allowed the design of pHSO probes that exhibited different
      dynamic pH range and possessed slightly different transition midpoint between i
      motif and open loop configuration. Moreover, this conformational transition was
      accompanied by spectral changes showing developed probes different pyrene excimer
      monomer emission ratio triggered by pH changes. The potential of these MBs for
      intracellular pH sensing is demonstrated on the example of HeLa cells line.

PMID- 29029741
TI  - Enantioseparation of single layer native cyclodextrin chiral stationary phases:
      Effect of cyclodextrin orientation and a modeling study.
AB  - A novel native cyclodextrin (CD) chiral stationary phase (CSP) with single
      triazole-bridge at CD C2 position (CSP1) was prepared by anchoring mono(2A-azido
      2A-deoxy)-beta-CD onto alkynyl silica via click chemistry. The effect of CD
      orientation on single layer CD-CSP's enantioseparation was comprehensively
      investigated using CSP1 (reversed orientation) and our previously reported CSP2
      (C6 single triazole-bridge, normal orientation) as well as a commercial CD-CSP
      (Cyclobond I 2000, hybrid orientation) by separating several groups of analytes
      in chiral high performance liquid chromatography. It is found that the CD
      orientation on silica surface plays an important role in separating different
      racemates. CSP2 with normal CD orientation affords best separation for
      isoxazolines while CSP1 with reversed CD orientation better separates naringenin,
      hesperetin and Troger's base. CSP2 and Cyclobond I 2000 show comparable
      separation ability for dansyl amino acids while poor separation was found on
      CSP1. Besides, molecular dynamics simulation was performed under "real"
      separation conditions using flavanone as model analyte to reveal the essential
      factors for CD's chiral discrimination behaviors.

PMID- 29029740
TI  - A quantitative homogeneous assay for global DNA methylation levels using CpG
      binding domain- and methyl-CpG-binding domain-fused luciferase.
AB  - Global DNA methylation levels have been considered as biomarkers for cancer
      diagnostics because transposable elements that constitute approximately 45% of
      the human genome are hypomethylated in cancer cells. We have previously reported
      a homogeneous assay for measuring methylated CpG content of genomic DNA based on
      bioluminescence resonance energy transfer (BRET) using methyl-CpG-binding domain
      (MBD)-fused luciferase (MBD-luciferase). In this study, a homogeneous assay for
      measuring unmethylated CpG content of genomic DNA in the same platform was
      developed using CXXC domain-fused luciferase (CXXC-luciferase) that specifically
      recognizes unmethylated CpG. In this assay, CXXC-luciferase recognizes
      unmethylated CpG on genomic DNA, whereby BRET between luciferase and the
      fluorescent DNA intercalating dye is detected. We demonstrated that the BRET
      signal depended on the genomic DNA concentration (R2 = 0.99) and unmethylated CpG
      content determined by the bisulfite method (R2 = 0.97). There was a significant
      negative correlation between the BRET signal of the CXXC-luciferase-based assay
      and that of the MBD-luciferase-based assay (R2 = 0.92). Moreover, we demonstrated
      that the global DNA methylation level determined using the bisulfite method was
      dependent on the ratio of the BRET signal in the MBD-luciferase-based assay to
      the total BRET signal in the MBD-luciferase- and CXXC-luciferase-based assays (R2
      = 0.99, relative standard deviation < 2.2%, and analysis speed < 35 min). These
      results demonstrated that global DNA methylation levels can be quantified by
      calculating the BRET signal ratio without any calibration curve.

PMID- 29029742
TI  - Preparative isoelectric focusing of microorganisms in cellulose-based separation
      medium and subsequent analysis by CIEF and MALDI-TOF MS.
AB  - Pre-separation and pre-concentration of bacteria is an important step especially
      when they are uncultured and bacterial concentration in the matrix is low. This
      study describes a preparative method based on isoelectric focusing of colored
      microorganisms in a cellulose-based separation medium from a high conductivity
      matrix. The isoelectric points found for the examined cells were 1.8 for
      Micrococcus luteus, 3.5 for Dietzia sp., and 4.7 for Rhodotorula mucilaginosa
      using capillary isoelectric focusing. The final positions of the zones of colored
      microbial cells in the cellulose-bed are indicated by colored pI markers.
      Segments of the separation medium with cells were harvested by a spatula, simply
      purified using centrifugation and analyzed by capillary isoelectric focusing and
      matrix-assisted laser desorption/ionization time of flight mass spectrometry. The
      determined recovery ranged from 78% to 93%. The viability of the harvested cells
      was verified by their cultivation.

PMID- 29029743
TI  - Advances of Vibrational Circular Dichroism (VCD) in bioanalytical chemistry. A
      review.
AB  - Vibrational Circular Dichroism (VCD) is a unique and relatively new spectroscopic
      technique that is capable of determining an absolute configuration of chiral
      molecules. VCD can be also used to determine structure of large macromolecules.
      This review highlights the most recent advances of VCD in bioanalytical
      chemistry. It shows that VCD is capable of unraveling supramolecular organization
      of peptides, proteins, saccharides, glycerophospholipids, polypeptide
      microcrystals, as well as amyloid fibrils and DNA. This review also demonstrates
      how VCD can be utilized to explore molecule-molecule interactions that determine
      mechanisms of chiral separations in chromatography. It aims to attract attention
      of scientists from all different research areas demonstrating the strength and
      capability of this very powerful spectroscopic technique.

PMID- 29029744
TI  - Hydrogels of polyaniline with graphene oxide for highly sensitive electrochemical
      determination of lead ions.
AB  - Conducting polymers with graphene/graphene oxide hydrogels represent a unique
      class of electrode materials for sensors and energy storage applications. In this
      article, we report a facile in situ method for the polymerisation of aniline
      resulting in the decoration of 1D conducting polyaniline (PANI) nanofibers onto
      the surface of 2D graphene oxide (GO) nanosheets followed by hydrogel formation
      at elevated temperature. The synthesized nanomaterial exhibits significant
      properties for the highly sensitive electrochemical determination as well as
      removal of environmentally harmful lead (Pb2+) ions. The square wave anodic
      stripping voltammetry (SWASV) determination of Pb2+ ions showed good
      electroanalytical performance with two linear ranges in 0.2-250 nM (correlation
      coefficient = 0.996) and 250-3500 nM (correlation coefficient = 0.998). The
      developed protocol has shown a limit of detection (LOD) of about 0.04 nM, which
      is much lower than that of the World Health Organization (WHO) threshold limits.
      The prepared electrode showed an average of ~99.4% removal of Pb2+ ions with a
      relative standard deviation (RSD) of 3.4%. Selectivity of the electrode towards
      Pb2+ ions were tested in presence of potential interferences such as Na+, K+,
      Ca2+, Mg2+, Cu2+, Cd2+, Hg2+, Zn2+, Co2+, Ni2+, Fe2+ and Fe3+ of similar and
      higher concentrations. The sensor showed good repeatability and reproducibility.
      The developed protocol was used to analyse samples from industrial effluents and
      natural water samples. The results obtained were correlated with atomic
      absorption spectroscopy (AAS).

PMID- 29029745
TI  - Synthesis of robust electrochemical substrate and fabrication of immobilization
      free biosensors for rapid sensing of salicylate and beta-hydroxybutyrate in whole
      blood.
AB  - An electrochemical latent redox probe, SAF 5 was designed, synthesized and
      characterized. A rapid and sensitive solution-based assay was demonstrated for
      salicylate hydroxylase (SHL). In presence of NADH at aerobic conditions, SHL
      catalyzed the decarboxylative hydroxylation of SAF and released a redox reporter
      amino ferrocene (AF 6). The release of AF 6 was monitored at interference free
      potential region (-50 mV vs. Ag|AgCl) using differential pulse voltammetry as
      signal read-out. The current signal generated by this process is highly specific,
      and insensitive to other biological interfering compounds. Next, the SAF
      incorporated SHL assay was extended to fabricate immobilization-free biosensors
      for rapid sensing of salicylic acid (SA) and beta-hydroxybutyrate (beta-HB) in
      whole blood. The described method rapidly detects SA in a linear range of 35-560
      MUM with detection limit of 5.0 MUM. For beta-HB determination, the linear range
      was 10-600 MUM and detection limit was 2.0 MUM. Besides, the assay protocols are
      simple, fast, reliable, selective, sensitive and advantageous over existing
      methods. The whole blood assay did not required cumbersome steps such as, enzyme
      immobilization, pre-treatments and holds great practical potential in clinical
      diagnosis.

PMID- 29029748
TI  - Insufficient evidence for the effectiveness of nonfluoride agents on caries
      prevention in primary dentition.

PMID- 29029746
TI  - Liquid chromatography tandem mass spectrometric determination of triterpenes in
      human fluids: Evaluation of markers of dietary intake of olive oil and metabolic
      disposition of oleanolic acid and maslinic acid in humans.
AB  - Olive oil is rich in several minor components like maslinic (MA) and oleanolic
      (OA) acids which have cardioprotective, antitumor, and anti-inflammatory
      properties. In order to assess the health benefits in humans provided by the
      olive oil triterpenes (MA and OA), suitable analytical methods able to quantify
      the low concentrations expected in human fluids are required. In this study, the
      LC-MS/MS quantification of both OA and MA in plasma and urine has been evaluated.
      The plasmatic method is based on the direct determination of the analytes. The
      urinary detection requires more sensitivity which was reached by derivatization
      with 2-picolylamine. Additionally, the urinary species present after MA and OA
      ingestion were evaluated by the direct detection of several phase II metabolites
      previously synthesized. Our results showed that OA is metabolized as both sulfate
      and glucuronide conjugates whereas MA is mainly excreted as glucuronide. Based on
      this information, the method for the urinary detection of MA and OA involved an
      enzymatic hydrolysis. Both plasmatic and urinary methods were validated with
      suitable precision and accuracy at all tested levels. Required sensitivity was
      achieved in both matrices. Up to our knowledge, this is the first method able to
      quantify the low concentration levels of triterpenes present in urine. Samples
      from two healthy volunteers who received virgin olive oils with different
      triterpenes content were analyzed. Some preliminary clues on the metabolic
      disposition of OA and MA after olive oil intake are provided.

PMID- 29029747
TI  - An alignment algorithm for LC-MS-based metabolomics dataset assisted by MS/MS
      information.
AB  - Liquid chromatography-mass spectrometry (LC-MS) is an important analytical
      platform for metabolomics study. Peak alignment of metabolomics dataset is one of
      the keys for a successful metabolomics study. In this work, a MS/MS-based peak
      alignment method for LC-MS metabolomics data was developed. A rigorous strategy
      for screening endogenous reference variables was proposed. Firstly, candidate
      endogenous reference variables were selected based on MS, MS/MS and retention
      time in all samples. Multiple robust endogenous reference variables were obtained
      through further evaluation and confirmation. Then retention time of each
      metabolite feature was corrected by local linear regression using the four
      nearest neighbor robust reference variables. Finally, peak alignment was carried
      out based on corrected retention time, MS and MS/MS. Comparing with the other two
      peak alignment methods, the developed method showed a good performance and was
      suitable for metabolomics data with larger retention time drift. Our approach
      provides a simple and robust alignment method which is reliable to align LC-MS
      metabolomics dataset.

PMID- 29029749
TI  - Titanium-zirconium narrow-diameter implants may have high survival rates after 1
      year.

PMID- 29029750
TI  - No differences important to patients between orthodontic treatment with
      customized fixed appliances and conventional appliances.

PMID- 29029751
TI  - Molar-incisor hypomineralization seems to be associated with caries experience,
      but the magnitude of this association is yet to be reliably determined.

PMID- 29029752
TI  - Low-level laser therapy may not provide any benefit in preventing and minimizing
      tooth sensitivity after dental bleaching.

PMID- 29029753
TI  - Decision aid did not reduce decision conflict in adolescents considering
      receiving orthodontic treatment with fixed appliances at an orthodontic clinic.

PMID- 29029754
TI  - Oral pathology patterns in late farmers of the Central Andes: A comparative
      perspective between coastal and highland populations.
AB  - Aiming at future comparisons with earlier hunter-gatherers or transitional
      populations, this paper intends to characterize and describe the oral pathology
      pattern of late agriculturalists from Central Andes dating to the Late
      Intermediate Period (LIP) and Inca periods (1000-1532 CE), and identify
      differences and/or similarities between coastal and highland populations.
      Although the botanical inventories of the LIP suggest carbohydrate-rich diets and
      similar components, it has been hypothesized that coastal and highland
      populations had, nevertheless, substantially different oral pathology patterns.
      We evaluated 14 indicators of oral pathology from Los Pinos (n=200) and Armatambo
      (n=25) sites in the Central Coast and two chronological phases from Laguna de los
      Condores site (LC-Inca, n=23; and LC-LIP, n=55), in the Peruvian northern
      highlands. The results showed a recurrent pattern of oral pathologies
      characterized by cervical caries (above 30%), extra-occlusal caries (above 60%),
      high rates of gross-gross caries, high frequency of ante mortem tooth loss, and
      signals of periodontal disease among these four populations. The diets of the
      coast were slightly more abrasive than those of the highlands. Oral pathology
      patterns were compatible with a slightly more cariogenic diet in the coast than
      in the highlands. In all four populations, those patterns were modulated by other
      common factors such as consumption of fermented drinks (maize beer - chicha) and
      the coca leaf chewing habit.

PMID- 29029755
TI  - Giant parathyroid lesion.

PMID- 29029756
TI  - Does prehospital care influence the profile of patients with acute cardiac
      failure?

PMID- 29029757
TI  - Palliative care and end-of-life care for polypathological patients.
AB  - Patients with advanced chronic diseases receive fragmented care, which entails
      high resource consumption and a poor quality of life. Uncertainty in the
      prognosis and scarce investigation into the importance of symptomatic control in
      this patient group hinders a proper therapeutic approach. Palliative care teams
      optimise the use of resources through comprehensive patient care, the
      optimization of the patient's environment, communication, the preparation of
      early care plans and the creation of coordinated healthcare circuits, which
      improve the quality of the patient's care in advanced stages of the disease. In
      the end-of-life phase, the therapeutic approach is focused on symptomatic
      control, selecting treatments according to the cause, comorbidities and the
      patient's wishes. To control refractory symptoms, palliative sedation is
      considered an indispensable option.

PMID- 29029758
TI  - Aspergillus flavus infection in an aortic graft: Imaging findings.

PMID- 29029759
TI  - Patient-centered research priorities in ovarian cancer: A systematic review of
      potential determinants of guideline care.
AB  - OBJECTIVE: To (a) determine what is known about the individual and contextual
      factors that may influence whether a woman with ovarian cancer receives guideline
      care, and (b) identify patient-centered research priorities in ovarian cancer.
      METHODS: A systematic review of the PubMed, MEDLINE, CINAHL Complete, and
      PsycInfo online databases. Eligible articles were published in English, described
      original research, and either (a) identified factors associated with the receipt
      of guideline care for ovarian cancer, or (b) described treatment decision making
      by women with ovarian cancer. Studies were excluded in which women with ovarian
      cancer did not comprise the entire sample of patient participants. Data were
      collected in accordance with Garrard's Matrix Method. Study quality was evaluated
      using the QualSyst tool for evaluating primary research papers. Relevant study
      findings were imported into NVivo Pro 11 for qualitative synthesis. RESULTS: The
      search strategy yielded 502 unique citations, of which 78 full-text articles were
      reviewed. Thirty-three articles met the criteria for inclusion. Study quality was
      high overall. Factors associated with the receipt of guideline care included race
      and ethnicity, socioeconomic status, insurance type, age, comorbidity, disease
      stage, tumor characteristics, hospital volume, hospital type, physician volume,
      and geographic location. Influences on treatment decision making among women with
      ovarian cancer included the desire to prolong survival, the patient-provider
      relationship, perceived ability to participate in the treatment decision, values
      and preferences, information needs, side effects, cost of care, and past
      experiences with chemotherapy. CONCLUSIONS: There is a need for further research
      that examines ovarian cancer treatment decision making from the perspective of
      the patient. Priority topics for future research may include the experiences of
      diverse women receiving treatment for ovarian cancer and the role of shared
      decision making with providers, referral networks, and practice patterns in the
      delivery of guideline care.

PMID- 29029760
TI  - [Pulmonary function alteration in laparoscopic surgery with pneumoperitoneum and
      abdominal wall elevation].

PMID- 29029761
TI  - Multiple effects of a Gracilaria vermiculophylla invasion on estuarine mudflat
      functioning and diversity.
AB  - The invasive Japanese seaweed Gracilaria vermiculophylla has become established
      over the past several years in numerous European estuaries, from Portugal to
      Norway. In the Faou estuary (48.295 degrees N-4.179 degrees W, Brittany, France),
      it forms a dense population at the mud's surface. The effects of G.
      vermiculophylla on metabolism, diversity, and the food web were studied.
      Community gross primary production (GPP) and respiration (CR) during emersion,
      chlorophyll-a content, macrofaunal and meiofaunal diversity and abundance, and
      stable isotopes (delta13C and delta15N) of representative macrofaunal species and
      main food sources were measured at low tide in winter, spring, summer 2014, and
      winter 2015. Results show significant seasonal variation in GPP and CR. Moreover,
      GPP was significantly higher in areas where G. vermiculophylla was present than
      in the control area (bare mud). However, this high GPP appeared to be linked to
      the increase in biomass in primary producers, with their efficiency (primary
      productivity, i.e. assimilation number) remaining relatively stable compared with
      the control area. Significant variation in abundance of meiofauna and macrofauna
      was also detected and new epifaunal species were collected, mainly in Gracilaria
      colonized areas. Isotopic food-web Bayesian mixing models strongly suggested that
      G. vermiculophylla plays a major role in the diet of some dominant species.
      Mechanisms interacting with the functioning and diversity of the mudflat are
      discussed. Finally, the invasive seaweed G. vermiculophylla affected the mudflat
      ecosystem in three ways: as a new primary producer (increase in metabolism), as a
      habitat-forming species (changes in diversity and abundance of macrofauna and
      meiofauna), and as a new abundant food source, likely through the detrital
      pathway.

PMID- 29029762
TI  - Thinner cortex in patients with subjective cognitive decline is associated with
      steeper decline of memory.
AB  - We aimed to investigate associations between regional cortical thickness and rate
      of decline over time in 4 cognitive domains in patients with subjective cognitive
      decline (SCD). We included 233 SCD patients with the total number of 654
      neuropsychological assessments (median = 3, range = 2-8) and available baseline
      magnetic resonance imaging from the Amsterdam Dementia Cohort (125 males, age: 63
      +/- 9, Mini-Mental State Examination score: 28 +/- 2). We assessed longitudinal
      cognitive functioning at baseline and follow-up in 4 cognitive domains (composite
      Z-scores): memory, attention, executive function, and language. Thickness
      (millimeter) was estimated using FreeSurfer for frontal, temporal, parietal,
      cingulate, and occipital cortices. We used linear mixed models to estimate
      effects of cortical thickness on cognitive performance (dependent variables).
      There were no associations between cortical thickness and baseline cognition, but
      a faster subsequent rate of memory loss was associated with thinner cortex of the
      frontal [beta (SE) = 0.20 (0.07)], temporal [beta (SE) = 0.18 (0.07)], and
      occipital [beta (SE) = 0.22 (0.09)] cortices (all p < 0.05FDR). These findings
      illustrate that early cortical changes, particularly in the temporal cortex,
      herald incipient cognitive decline related to neurodegenerative diseases, most
      prominently Alzheimer's disease.

PMID- 29029763
TI  - Serotype, virulence profile, antimicrobial resistance and macrolide-resistance
      determinants in Streptococcus agalactiae isolates in pregnant women and neonates
      in Catalonia, Spain.
AB  - INTRODUCTION: Streptococcus agalactiae, or group B streptococci (GBS), is the
      main aetiological agent of early neonatal sepsis in developed countries. This
      microorganism belongs to the gastrointestinal tract microbiota wherefrom it can
      colonize the vagina and be vertically transmitted to the child either before or
      at birth, and subsequently cause infection in the newborn. Approximately, 50% of
      newborns born to women with GBS become colonized, with 1-2% developing early
      neonatal infection if no preventive intervention is performed. The aim of this
      study was to characterize and compare serotypes, virulence factors and
      antimicrobial resistance of GBS isolates collected from pregnant women and
      newborns in several hospitals in Catalonia. METHODS: 242 GBS strains were
      analyzed including 95 colonizers and 68 pathogenic strains isolated from pregnant
      women, and 79 strains isolated from neonates with sepsis in order to determine
      serotype, virulence and antimicrobial resistance. RESULTS: Serotype distribution
      was different among the three groups, with serotypes Ia and II being
      significantly more frequent among colonizing strains (p=0.001 and 0.012,
      respectively). Virulence factors bca and scpB were significantly more frequent
      among neonatal strains than pathogenic or colonizing strains (p=0.0001 and 0.002,
      respectively). Pathogenic strains were significantly more resistant to
      erythromycin, clindamycin and azithromycin than their non-pathogenic
      counterparts. CONCLUSIONS: Taking into account that neonatal sepsis represents a
      significant problem on a global scale, epidemiological surveillance,
      antimicrobial resistance and GBS virulence at the local level could provide
      important knowledge about these microorganisms as well as help to improve
      treatment and prevent invasive infection caused by this microorganism.

PMID- 29029764
TI  - Application of ISOCS system in the laboratory efficiency calibration.
AB  - ISOCS (In Situ Counting Object System) from Canberra is applied in laboratory for
      creating efficiency calibrations of good quality without using radioactive
      standards. Besides of typical sample containers used in laboratory, ISOSC system
      also allows modelling containers and objects of almost any shape and elemental
      composition. The study was based on gamma spectrometry with HPGe semiconductor
      detector with electronics and software spectrum analysis GENIE 2000 + ISOCS.
      Measuring set is equipped with portable shield system with set of collimators
      ISOCS Shield Systems Model ISOXSHLD from Canberra. This shielding system provides
      attenuation of gamma background radiation with average value 33 (for gamma
      energies from 186 keV to 2615.5 keV). The portable shield system can be used for
      low-background laboratory measurements. For this purpose a measuring vessel of
      new geometry was constructed: the polystyrene cylinder with a height of 40 mm and
      a diameter of 70 mm. The efficiency calibration for this container was performed
      using both ISOCS system and classical calibration standard in the same geometry.
      In order to verify the correctness of performed calibration procedures, the
      measurements of radioactive standard CBSS 2 were made. The results of both
      calibrations were compared with the data from the standard certificate.
      Satisfactory agreement was achieved. Mean percentage difference between results
      from ISOCS calibration compared to reference values is 6% for all isotopes
      activities in CBSS 2 standard. The set of collimators was used to develop
      efficiency calibration for in situ measurements of the soil surface. Test
      measurements were carried out at the area of the Institute of Nuclear Physics
      Polish Academy of Sciences in Krakow, Poland (IFJ PAN). Two measurement methods
      were compared: in situ and laboratory gamma spectroscopy. The obtained average
      results (from all 10 measuring points) are consistent within the range of
      measurement uncertainty.

PMID- 29029765
TI  - Radioactive and stable cesium isotope distributions and dynamics in Japanese
      cedar forests.
AB  - Dynamics of the Fukushima-derived radiocesium and distribution of the natural
      stable isotope 133Cs in Japanese cedar (Cryptomeria japonica D. Don) forest
      ecosystems were studied during 2014-2016. For the experimental site in Yamakiya,
      Fukushima Prefecture, we present the redistribution of radiocesium among
      ecosystem compartments during the entire observation period, while the results
      obtained at another two experimental site were used to demonstrate similarity of
      the main trends in the Japanese forest ecosystems. Our observations at the
      Yamakiya site revealed significant redistribution of radiocesium between the
      ecosystem compartments during 2014-2016. During this same period radionuclide
      inventories in the aboveground tree biomass were relatively stable, however,
      radiocesium in forest litter decreased from 20 +/- 11% of the total deposition in
      2014 to 4.6 +/- 2.7% in 2016. Radiocesium in the soil profile accumulated in the
      5-cm topsoil layers. In 2016, more than 80% of the total radionuclide deposition
      in the ecosystem resided in the 5-cm topsoil layer. The radiocesium distribution
      between the aboveground biomass compartments at Yamakiya during 2014-2016 was
      gradually approaching a quasi-equilibrium distribution with stable cesium. Strong
      correlations of radioactive and stable cesium isotope concentrations in all
      compartments of the ecosystem have not been reached yet. However, in some
      compartments the correlation is already strong. An increase of radiocesium
      concentrations in young foliage in 2016, compared to 2015, and an increase in
      2015-2016 of the 137Cs/133Cs concentration ratio in the biomass compartments with
      strong correlations indicate an increase in root uptake of radiocesium from the
      soil profile. Mass balance of the radionuclide inventories, and accounting for
      radiocesium fluxes in litterfall, throughfall and stemflow, enabled a rough
      estimate of the annual radiocesium root uptake flux as 2 +/- 1% of the total
      inventory in the ecosystem.

PMID- 29029767
TI  - PET/CT and PET/MRI in head and neck malignancy.
AB  - Combined 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography
      (PET)/computed tomography (CT) has an established role in the staging of
      difficult cases of head and neck (HN) squamous cell carcinoma (SCC), looking for
      an unknown primary, assessing response post-chemotherapy at 3-6 months, and
      differentiating relapse from treatment effects in patients suspected to have
      tumour recurrence. The PET NECK trial, comparing PET/CT surveillance versus neck
      dissection in advanced head and neck cancer showed survival was similar among
      patients who underwent PET/CT-guided surveillance and those who underwent planned
      neck dissection, but surveillance was more cost-effective. There is growing
      interest in the use of hypoxia PET tracers, especially in targeting radiotherapy,
      where the radiotherapy dose can be boosted in regions of hypoxia; the use of 68Ga
      peptide tracers in neuroendocrine malignancy and also in the growing field of
      combined PET/magnetic resonance imaging (MRI). PET/MRI has the advantage of
      increased anatomical detail and radiation dose reduction combined with the
      molecular and metabolic data from PET, although PET/CT has the advantage in
      better sensitivity for imaging lung metastases. Thus far, there is good agreement
      between PET/CT and PET/MRI with high correlation between semi-quantitative
      measurements in primary, nodal, osseous, and soft-tissue lesions imaging. PET/MRI
      may indeed provide greater accuracy than the currently available imaging
      procedures in the staging and later treatment response evaluation in HNSCC.

PMID- 29029766
TI  - Diagnostic performance of gadofosveset-enhanced axillary MRI for nodal
      (re)staging in breast cancer patients: results of a validation study.
AB  - AIM: To evaluate diagnostic performance of gadofosveset (GDF)-enhanced magnetic
      resonance imaging (MRI) in addition to T2-weighted (T2W) MRI for nodal
      (re)staging in newly diagnosed breast cancer patients. MATERIALS AND METHODS:
      Ninety patients underwent axillary T2W- and GDF-MRI. Two radiologists
      independently scored each lymph node; first on T2W-MRI, subsequently adjusting
      their score on GDF-MRI. Diagnostic performance parameters were calculated on node
      by-node and patient-by-patient validation with histopathology as the reference
      standard. Furthermore, learning curve analysis for reading GDF-MRI was performed.
      RESULTS: In patient-by-patient validation, overall reader performances for T2W-
      and GDF-MRI were similar with area under the receiver operating characteristic
      curves (AUC) of 0.75 and 0.77 (p=0.731) for reader 1 and 0.79 and 0.72 (p=0.156)
      for reader 2. For node-by-node validation, AUC values of T2W- and GDF-MRI were
      0.76 and 0.82 (p=0.018) and 0.77 and 0.77 (p=0.998) for reader 1 and 2. The AUC
      for reader 1 was 0.71 for first one-third of nodes evaluated, improving to 0.80
      and 0.95 for the next and last one-third, respectively. Sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV) improved
      from 38%, 89%, 56%, and 79% to 60%, 93%, 64%, and 92%. The AUC of reader 2
      improved from 0.69 to 0.79. CONCLUSION: The present study confirmed that GDF-MRI,
      in addition to T2W-MRI, has potential as a non-invasive method for nodal
      (re)staging in breast cancer.

PMID- 29029769
TI  - Role of imaging techniques in the diagnosis and follow-up of muscle-invasive
      bladder carcinoma.
AB  - INTRODUCTION: Muscle-invasive bladder malignancies represent 20-30% of all
      bladder cancers. These patients require imaging tests to determine the regional
      and distant staging. OBJECTIVE: To describe the role of various imaging tests in
      the diagnosis, staging and follow-up of muscle-invasive bladder cancer. To assess
      recent developments in radiology aimed at improving the sensitivity and
      specificity of local staging and treatment response. ACQUISITION OF EVIDENCE: We
      conducted an updated literature review. SYNTHESIS OF THE EVIDENCE: Computed
      tomography and magnetic resonance imaging (MRI) are the tests of choice for
      performing proper staging prior to surgery. Computed tomography urography is
      currently the most widely used technique, although it has limitations in local
      staging. Ultrasonography still has a limited role. Recent developments in MRI
      have improved its capacity for local staging. MRI has been suggested as the test
      of choice for the follow-up, with promising results in assessing treatment
      response. Positron emission tomography could improve the detection of
      adenopathies and extrapelvic metastatic disease. CONCLUSIONS: Imaging tests are
      essential for the diagnosis, staging and follow-up of muscle-invasive bladder
      cancer. Recent technical developments represent important improvements in local
      staging and have opened the possibility of assessing treatment response.

PMID- 29029770
TI  - Why women are not small men.

PMID- 29029768
TI  - Value of 100 kVp scan with sinogram-affirmed iterative reconstruction algorithm
      on a single-source CT system during whole-body CT for radiation and contrast
      medium dose reduction: an intra-individual feasibility study.
AB  - AIM: To perform an intra-individual investigation of the usefulness of a contrast
      medium (CM) and radiation dose-reduction protocol using single-source computed
      tomography (CT) combined with 100 kVp and sinogram-affirmed iterative
      reconstruction (SAFIRE) for whole-body CT (WBCT; chest-abdomen-pelvis CT) in
      oncology patients. MATERIALS AND METHODS: Forty-three oncology patients who had
      undergone WBCT under both 120 and 100 kVp protocols at different time points
      (mean interscan intervals: 98 days) were included retrospectively. The CM doses
      for the 120 and 100 kVp protocols were 600 and 480 mg iodine/kg, respectively;
      120 kVp images were reconstructed with filtered back-projection (FBP), whereas
      100 kVp images were reconstructed with FBP (100 kVp-F) and the SAFIRE (100 kVp
      S). The size-specific dose estimate (SSDE), iodine load and image quality of each
      protocol were compared. RESULTS: The SSDE and iodine load of 100 kVp protocol
      were 34% and 21%, respectively, lower than of 120 kVp protocol (SSDE: 10.6+/-1.1
      versus 16.1+/-1.8 mGy; iodine load: 24.8+/-4versus 31.5+/-5.5 g iodine, p<0.01).
      Contrast enhancement, objective image noise, contrast-to-noise-ratio, and visual
      score of 100 kVp-S were similar to or better than of 120 kVp protocol.
      CONCLUSION: Compared with the 120 kVp protocol, the combined use of 100 kVp and
      SAFIRE in WBCT for oncology assessment with an SSCT facilitated substantial
      reduction in the CM and radiation dose while maintaining image quality.

PMID- 29029771
TI  - [Therapeutic itinerary and radiological features of positive microscopy
      tuberculosis patients at Centre Hospitalier National Universitaire de Fann
      (CHNUF), Dakar].
AB  - INTRODUCTION: The long diagnostic delay is responsible for the extension of
      radiological lesions and spread of TB in the community. These radiological
      lesions can leave significant scars responsible for respiratory disability.
      OBJECTIVE: The aim of the study is to characterize radiologic features according
      to tuberculosis diagnostic delay. METHODS: We conducted a prospective cross
      sectional study, about 66 patients with positive sputum. RESULTS: The average
      diagnostic delay was 16 (+/-15) weeks; whether 22 (+/-14.1) weeks in the female
      gender versus 14.6 (+/-14.3) weeks in the male gender (P=0.10). The first care
      use was respectively health centers (62.1%), drugstores (51.9%), and traditional
      medicine (28.7%). Only 27.2% of patients used the marabouts care. Bilateral
      radiographic abnormalities in bivariate analysis were associated with
      consultation at the health center (66.7% versus 33.3%; P<0.031), as is the
      extension of the lesions (70.2% versus 29.8% RP=1.66 [1.05 to 2.91]; P<0.03).
      Lake of knowledge of the symptoms of TB was associated with the use of marabouts
      care (12.5% versus 87.5; PR=0.35 [0.11 to 1.08], P<0.04). CONCLUSION: These
      results should prompt consideration in an emergency, appropriate control
      interventions, advocacy, patient information and medical personnel on the reality
      of tuberculosis to prevent its spread often causing respiratory disability with
      radological effects.

PMID- 29029773
TI  - Post-resuscitation myocardial injury: MRI and MDCT patterns.

PMID- 29029772
TI  - Inhibition of Mammalian Target of Rapamycin Signaling with Rapamycin Prevents
      Trauma-Induced Heterotopic Ossification.
AB  - A pressing clinical need exists for 63% to 65% of combat-wounded service members
      and 11% to 20% of civilians who develop heterotopic ossification (HO) after blast
      related extremity injury and traumatic injuries, respectively. The mammalian
      target of rapamycin pathway is a central cellular sensor of injury. We evaluated
      the prophylactic effects of rapamycin, a selective inhibitor of mammalian target
      of rapamycin signaling, on HO formation in a rat model of blast-related,
      polytraumatic extremity injury. Rapamycin was administered intraperitoneally
      daily for 14 days at 0.5 mg/kg or 2.5 mg/kg. Ectopic bone formation was monitored
      by micro-computed tomography and confirmed by histologic examination. Connective
      tissue progenitor cells, platelet-derived growth factor receptor-alpha-positive
      cells, and alpha-smooth muscle actin-positive blood vessels were assayed at
      postoperative day 7 by colony formation and immunofluorescence. Early gene
      expression changes were determined by low-density microarray. There was
      significant attenuation of 1) total new bone and soft tissue ectopic bone with
      0.5 mg/kg (38.5% and 14.7%) and 2.5 mg/kg rapamycin (90.3% and 82.9%),
      respectively, 2) connective tissue progenitor cells, 3) platelet-derived growth
      factor receptor-alpha-positive cells, 4) alpha-smooth muscle actin-positive blood
      vessels, and 5) of key extracellular matrix remodeling (CD44, Col1a1, integrins),
      osteogenesis (Sp7, Runx2, Bmp2), inflammation (Cxcl5, 10, IL6, Ccl2), and
      angiogenesis (Angpt2) genes. No wound healing complications were noted. Our data
      demonstrate the efficacy of rapamycin in inhibiting blast trauma-induced HO by a
      multipronged mechanism.

PMID- 29029774
TI  - Immediate coronary angiography in survivors of out-of-hospital cardiac arrest
      without obvious extracardiac cause: Who benefits?
AB  - BACKGROUND: Immediate coronary angiography (iCA) and primary percutaneous
      coronary angioplasty (pPCI) in patients successfully resuscitated after out-of
      hospital cardiac arrest (OHCA) of suspected cardiac cause is controversial. Our
      aims were to assess the results of iCA, the prognostic impact of pPCI after OHCA,
      and to identify subgroups most likely to benefit from this strategy. METHODS: In
      this single-centre retrospective study, patients aged >=18 years with sustained
      return of spontaneous circulation after OHCA and no evidence of a non-cardiac
      cause underwent routine iCA at admission, with pPCI if indicated. Results of iCA,
      and factors associated with in-hospital survival were analysed. RESULTS: Between
      2006 and 2013, 160 survivors from OHCA presumed of cardiac origin were included
      (median age, 60 years; 85% males). iCA showed significant coronary-artery lesions
      in 75% of patients, and acute occlusion or unstable lesion in only 41%. pPCI was
      performed in 34% of patients and was not associated with survival by univariate
      or multivariate analysis (P=0.67). ST-segment elevation predicted acute coronary
      occlusion in 40%. An initial shockable rhythm was associated with higher in
      hospital survival (52% vs. 19%; P<0.001). After initial defibrillation, the first
      rhythm recorded by 12-lead electrocardiography was highly associated with
      prognosis: secondary asystole had a very low survival rate (5%, 1/21) despite PCI
      in 43% of patients, compared to sustained ventricular tachycardia/fibrillation
      (42%, 15/36) and supraventricular rhythm (71%, 50/70) (P<0.001). CONCLUSIONS: In
      our experience, the prevalence of acute coronary occlusion or unstable lesion
      immediately after OHCA of likely cardiac cause is only 41%. Immediate CA in OHCA
      survivors, with pPCI if indicated, should be restricted to highly selected
      patients.

PMID- 29029775
TI  - [Management of NSTEMI in a hospital without interventional cardiology and without
      use of GRACE score: Does the clinician appreciation match the GRACE score
      calculated retrospectively for the coronarography delay?]
AB  - PURPOSE: The management of non-ST segment elevation acute coronary syndromes
      (NSTEACS) remains an issue for mobidity, mortality, and an economic stake. The
      first aim of the study was to evaluate the additional value of the GRACE score
      for the compliance with the recommended times to coronary angiography in an
      hospital without interventional cardiology. We also analysed the in-hospital and
      6-month mortality and the predictive factors of compliance for the coronarography
      delays. METHODS: Retrospective monocenter cross-sectional study including
      consecutive patients with chest pain suggestive of a NSTEACS during 1 year. Data
      of the delay to coronarography were collected and GRACE score was calculated a
      posteriori. RESULTS: The time to perform coronary angiography was non-compliant
      in 49% of cases (27 patients out of 55). The calculation of the GRACE score would
      have allowed correcting the delay for two patients of our cohort. Clinical
      appreciation, troponin elevation, ECG modifications were associated with the
      delay compliance. Age <75 years predisposed to recommended delays. Renal failure
      and history of coronaropathy were significantly associated with non compliant
      delays. A non-compliant delay was significantly associated with higher mortality.
      CONCLUSION: In our experience, the knowledge of the GRACE score had little impact
      on the timing of coronary angiography. However, as a predictor of mid and long
      term mortality, GRACE score remains SCA ST+ useful to intensify surveillance of
      high-risk patients.

PMID- 29029776
TI  - Accelerated idioventricular rhythm requiring catheter ablation in a child: The
      dark side of a benign arrhythmia.
AB  - A 12 year-old boy, with no history of cardiac disease, was referred to our
      department for evaluation of an incessant accelerated idioventricular rhythm
      (AIVR) complicated with severe left ventricular (LV) dysfunction and cardiogenic
      shock. Extensive diagnostic work-up failed to reveal any structural heart
      disease. During electrophysiological study, AIVR originated from the right
      ventricular endocardial anterior wall and was successfully ablated using remote
      magnetic navigation. LV function showed complete recovery four weeks after the
      procedure. This case highlights a life-threatening evolution of an arrhythmia
      generally presented as a benign entity in children.

PMID- 29029777
TI  - [Management of high-risk pulmonary embolism with pulmonary artery trunk mobile
      thrombus].
AB  - The presence of a right intraventricular thrombus is a marker of severity of
      pulmonary embolism (PE), and is associated with high mortality. We report the
      case of a young patient with a PE postoperative of patellar tendon surgery. The
      cardiac echocardiography at its admission revealed a voluminous mobile thrombus
      of 1.7cm diameter located on the pulmonary trunk. Systemic thrombolysis was
      performed because of respiratory deterioration allowing a rapid disappearance of
      the thrombus and recovery. Our case emphasizes the value of a complete ultrasound
      analysis centered on the pulmonary trunk in the case of intermediate-risk PE. No
      recommendation exists on the management of these right ventricular thrombi,
      thrombolysis appearing to be the first-line treatment.

PMID- 29029778
TI  - Discussion of: "Redefining the abdominal seatbelt sign: Enhanced CT imaging
      metrics improve injury prediction".

PMID- 29029779
TI  - Redefining the abdominal seatbelt sign: Enhanced CT imaging metrics improve
      injury prediction.
AB  - INTRODUCTION: The abdominal seatbelt sign (ASBS) has an established association
      with abdominal injury, yet its definition remains ill-defined. We hypothesize
      specific imaging characteristics associated with the ASBS such as location above
      the pelvic brim and depth of abdominal wall contusion would better predict
      underlying injury and need for operative intervention. METHODS: We performed a
      retrospective chart review of subjects suffering from restrained motor vehicle
      collisions (MVC) evaluated at a level one trauma facility from 2010 to 2015. CT
      imaging was reviewed for the presence of a transverse abdominal wall contusion
      consistent with lap belt use. Contusion location was determined in relation to
      the anterior superior iliac spine (ASIS). Abdominal wall thickness as well as
      contusion depth were measured at the contusion level and an abdominal seatbelt
      sign depth index (ASBSI) was calculated. RESULTS: Sample size for the cohort was
      551 subjects. Operative need was 19.73% in those with ASBS on CT (CT ASBS) above
      the ASIS and 4.05% (p-value < 0.01) in those with only clinical evidence of ASBS
      (CL ASBS). CT ASBS above the ASIS was associated with higher incidence of intra
      abdominal injuries (31.97% vs 16.45%; p = 0.01) and a higher rate of abdominal
      operations (19.73% vs. 7.59%; p < 0.01) compared to below the ASIS. In contrast,
      CT ASBS below the ASIS was associated with a higher incidence of pelvic fractures
      (17.72% vs. 8.16%; p = 0.01) with fractures being an independent risk factor for
      abdominal injury requiring intervention. Logistic regression analyses and
      receiver-operator characteristic curves demonstrated ASBSI was significantly
      associated with abdominal injury requiring operative intervention. CONCLUSION:
      Characteristics of abdominal wall injury on imaging such as location and
      contusion depth (ASBSI) are better predictors of abdominal operative need than
      standard clinical measures. This analysis substantiates a novel diagnostic tool
      which may have the potential to facilitate clinical diagnosis and management
      decisions in patients with abdominal seatbelt sign.

PMID- 29029780
TI  - Risk factors for surgical site infection after stoma closure comparison between
      pursestring wound closure and conventional linear wound closure: Propensity score
      matching analysis.
AB  - PURPOSE: Stoma closure has been associated with a high rate of surgical site
      infection (SSI) and the optimal skin closure method is still controversial. The
      aim of this study was to compare the short-term and long-term outcomes between
      the conventional linear closure (CC) and the persestring closure (PC) using
      propensity score matching analysis. METHODS: We analysed the data of 360 patients
      who underwent stoma closure with CC or PC between January 2000 and December 2014.
      The propensity score was calculated from age, gender, body mass index, primary
      disease, type of stoma, diabetes mellitus, history of smoking, steroid use, the
      American Society of Anesthesiologists score, Prognostic Nutritional Index and
      modified Glasgow Prognostic Score. RESULTS: There was no difference in operative
      variables between the two groups. The CC group and the PC group were comparable
      with regards to overall SSI (25.0 vs. 7.8%; P = 0.007), superficial SSI (21.9 vs.
      4.7%; P = 0.003). Significant risk factor for SSI was conventional linear closure
      (OR, 4.14; 95% CI, 1.448-13.91). CONCLUSION: Our study suggests that a
      pursestring stoma closure leads to less SSI.

PMID- 29029781
TI  - Discussion of: "Returning from the acidotic abyss: Mortality in trauma patients
      with a pH < 7.0".

PMID- 29029782
TI  - Discussion of: "A nationwide evaluation of robotic ventral hernia surgery".

PMID- 29029783
TI  - Follow-up trends after Emergency Department discharge for acutely symptomatic
      hernias.
AB  - BACKGROUND: Patients frequently present to the Emergency Department (ED) with
      symptomatic hernias. This study evaluated the outcomes of patients presenting
      with symptomatic hernias without indication for immediate operation who are
      discharged for elective repair. METHODS: A three-year retrospective analysis of
      patients discharged from the ED with a symptomatic hernia was performed at a
      university affiliated county referral center. The incidences of ED revisits,
      clinic follow up and repairs occurring in the elective versus emergency setting
      were assessed. RESULTS: There were 111 patients evaluated and discharged from the
      ED with a symptomatic hernia where 21% (23) were recurrent and 27% (30) were
      chronically incarcerated. Of the 111 patients only 23% (26) followed-up in clinic
      and only 18% (20) underwent hernia repair. However, 25% (28) of all patients
      required a return visit to the ED and 45% (9) of herniorrhaphies were emergent.
      CONCLUSIONS: Discharge and failure of follow-up after an ED visit for a
      symptomatic hernia leaves many patients at risk for recurrent ED visits and
      emergent surgery.

PMID- 29029786
TI  - Cell calcium special issue: Preface.

PMID- 29029785
TI  - A single dose of cocaine potentiates glutamatergic synaptic transmission onto
      locus coeruleus neurons.
AB  - The brainstem locus coeruleus (LC), the primary norepinephrinergic (NE) nucleus
      in the brain, has been implicated in the abuse of drugs such as opioids. However,
      whether and how the LC-NE system is involved in cocaine addiction remains
      elusive. Here, we demonstrated cocaine-evoked synaptic plasticity of
      glutamatergic transmission onto LC neurons as one of the earliest traces
      occurring after a single injection of cocaine. Twenty-four hours after mice were
      injected intraperitoneally with cocaine, the evoked alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid receptor (AMPAR) mediated synaptic transmission
      onto LC neurons were strongly potentiated without major effect on N-methyl-d
      aspartate receptor (NMDAR) mediated synaptic transmission. Compared with saline
      pretreated mice, AMPAR-mediated excitatory postsynaptic currents (EPSCs) of
      cocaine-pretreated mice showed a marked inward rectification, demonstrating the
      insertion of GluR2-lacking AMPARs to plasma membrane. In addition, the single
      injection of cocaine did not affect presynaptic glutamate release probability
      measured by paired pulse ratio. Furthermore, we found that the cocaine-induced
      potentiation of AMPAR EPSCs could be blocked by prazosin, an inhibitor of alpha1
      adrenoreceptor (AR), indicating that cocaine increases AMPAR transmission via
      alpha1-ARs. These results reveal that LC-NE serves as an initial target of drug
      intake.

PMID- 29029787
TI  - Early testosterone replacement attenuates intracellular calcium dyshomeostasis in
      the heart of testosterone-deprived male rats.
AB  - BACKGROUND: Testosterone deficiency in elderly men increases the risk of
      cardiovascular disease. In bilateral orchiectomized (ORX) animals, impaired
      cardiac Ca2+ regulation was observed, and this impairment could be improved by
      testosterone replacement, indicating the important role of testosterone in
      cardiac Ca2+ regulation. However, the temporal changes of Ca2+ dyshomeostasis in
      testosterone-deprived conditions are unclear. Moreover, the effects of early vs.
      late testosterone replacement are unknown. We hypothesized that the longer the
      deprivation of testosterone, the greater the impairment of cardiac Ca2+
      homeostasis, and that early testosterone replacement can effectively reduce this
      adverse effect. METHODS: Male Wistar rats were randomly divided into twelve
      groups, four sets of three. The first set were ORX for 2, 4 and 8 weeks, the
      second set were sham-operated groups of the same periods, the third set were ORX
      for 8 weeks coupled with a subcutaneous injection of vehicle (control),
      testosterone during weeks 1-8 (early replacement) or testosterone during weeks 5
      8 (late replacement), and finally the 12-week sham-operated, ORX and ORX treated
      with testosterone groups. Cardiac Ca2+ transients (n=4-5/group), L-type calcium
      current (ICa-L) (n=4/group), Ca2+ regulatory proteins (n=6/group) and cardiac
      function (n=5/group) were determined. RESULTS: In the ORX rats, impaired cardiac
      Ca2+ transients and reduced ICa-L were observed initially 4 weeks after ORX as
      shown by decreased Ca2+ transient amplitude, rising rate and maximum and average
      decay rates. No alteration of Ca2+ regulatory proteins such as the L-type Ca2+
      channels, ryanodine receptor type 2, Na+-Ca2+ exchangers and SERCA2a were
      observed. Early testosterone replacement markedly improved cardiac Ca2+
      transients, whereas late testosterone replacement did not. The cardiac
      contractility was also improved after early testosterone replacement.
      CONCLUSIONS: Impaired cardiac Ca2+ homeostasis is time-dependent after
      testosterone deprivation. Early testosterone replacement improves cardiac Ca2+
      transient regulation and contractility, suggesting the necessity of early
      intervention in conditions of testosterone-deprivation.

PMID- 29029784
TI  - Regulation of insulin exocytosis by calcium-dependent protein kinase C in beta
      cells.
AB  - The control of insulin release from pancreatic beta cells helps ensure proper
      blood glucose level, which is critical for human health. Protein kinase C has
      been shown to be one key control mechanism for this process. After glucose
      stimulation, calcium influx into beta cells triggers exocytosis of insulin
      containing dense-core granules and activates protein kinase C via calcium
      dependent phospholipase C-mediated generation of diacylglycerol. Activated
      protein kinase C potentiates insulin release by enhancing the calcium sensitivity
      of exocytosis, likely by affecting two main pathways that could be linked: (1)
      the reorganization of the cortical actin network, and (2) the direct
      phosphorylation of critical exocytotic proteins such as munc18, SNAP25, and
      synaptotagmin. Here, we review what is currently known about the molecular
      mechanisms of protein kinase C action on each of these pathways and how these
      effects relate to the control of insulin release by exocytosis. We identify
      remaining challenges in the field and suggest how these challenges might be
      addressed to advance our understanding of the regulation of insulin release in
      health and disease.

PMID- 29029788
TI  - Differential Ca2+ mobilization and mast cell degranulation by FcepsilonRI- and
      GPCR-mediated signaling.
AB  - Mast cells play a primary role in allergic diseases. During an allergic reaction,
      mast cell activation is initiated by cross-linking IgE-FcepsilonRI complex by
      multivalent antigen resulting in degranulation. Additionally, G protein-coupled
      receptors also induce degranulation upon activation. However, the spatio-temporal
      relationship between Ca2+ mobilization and mast cell degranulation is not well
      understood. We investigated the relationship between oscillations in Ca2+ level
      and mast cell degranulation upon stimulation in rat RBL-2H3 cells. Nile red and
      Fluo-4 were used as probes for monitoring histamine and intracellular Ca2+
      levels, respectively. Histamine release and Ca2+ oscillations in real-time were
      monitored using total internal reflection fluorescence microscopy (TIRFM). Mast
      cell degranulation followed immediately after FcepsilonRI and GPCR-mediated Ca2+
      increase. FcepsilonRI-induced Ca2+ increase was higher and more sustained than
      that induced by GPCRs. However, no significant difference in mast cell
      degranulation rates was observed. Although intracellular Ca2+ release was both
      necessary and sufficient for mast cell degranulation, extracellular Ca2+ influx
      enhanced the process. Furthermore, cytosolic Ca2+ levels and mast cell
      degranulation were significantly decreased by downregulation of store-operated
      Ca2+ entry (SOCE) via Orai1 knockdown, 2-aminoethyl diphenylborinate (2-APB) or
      tubastatin A (TSA) treatment. Collectively, this study has demonstrated the role
      of Ca2+ signaling in regulating histamine degranulation.

PMID- 29029789
TI  - Vesicle fusion and fission in plants and yeast.
AB  - Measurements of the membrane capacitance on animal cells has provided an
      excellent technique for monitoring of exo- and endocytotic activity in intact
      living cells. Here we review recent data in which the same technique was applied
      to plant cells and cells of the budding yeast Saccharomyces cerevisiae. The data
      show that unitary exo- and endocytotic events can also be measured with the same
      technique after removing the cell wall from these cells. The resulting
      protoplasts execute the same type of transient and permanent fusion/fission that
      is known from animal cells. Also the size of the vesicles, which are fusing or
      budding, are of the same order of magnitude as those recorded in animal cells.
      Together these data support the view of an evolutionary conserved mechanism for
      unitary exo- and endocytosis events in eukaryotes. The successful recordings of
      exo- and endocytotic activity in Saccharomyces cerevisiae by capacitance
      measurements now pave the way for correlating the abundant information on the
      molecular machinery of exo- and endocytosis in this model organism with distinct
      functional properties.

PMID- 29029790
TI  - Dynamics of surface neurotransmitter receptors and transporters in glial cells:
      Single molecule insights.
AB  - The surface dynamics of neurotransmitter receptors and transporters, as well as
      ion channels, has been well-documented in neurons, revealing complex molecular
      behaviour and key physiological functions. However, our understanding of the
      membrane trafficking and dynamics of the signalling molecules located at the
      plasma membrane of glial cells is still in its infancy. Yet, recent breakthroughs
      in the field of glial cells have been obtained using combination of
      superresolution microscopy, single molecule imaging, and electrophysiological
      recordings. Here, we review our current knowledge on the surface dynamics of
      neurotransmitter receptors, transporters and ion channels, in glial cells. It has
      emerged that the brain cell network activity, synaptic activity, and calcium
      signalling, regulate the surface distribution and dynamics of these molecules.
      Remarkably, the dynamics of a given neurotransmitter receptor/transporter at the
      plasma membrane of a glial cell or neuron is unique, revealing the existence of
      cell-type specific regulatory pathways. Thus, investigating the dynamics of
      signalling proteins at the surface of glial cells will likely shed new light on
      our understanding of glial cell physiology and pathology.

PMID- 29029791
TI  - In search for globally disordered apo-parvalbumins: Case of parvalbumin beta-1
      from coho salmon.
AB  - Parvalbumin (PA) is a classical EF-hand calcium-binding protein of muscle,
      neuronal, and other tissues, and a major fish allergen. Although certain apo-PAs
      lack tertiary structure, functional implications of that feature and its
      structural prerequisites remain unclear. In a search for unstable PAs, we probed
      conformational stability of parvalbumin beta-1 from coho salmon (csPA), a cold
      water fish species, using circular dichroism, scanning calorimetry, hydrophobic
      probe fluorescence, limited proteolysis, chemical crosslinking and dynamic light
      scattering techniques. Apo-csPA is shown to be mainly monomeric protein with
      markedly disorganized secondary structure and lack of rigid tertiary structure.
      Examination of per-residue propensity for intrinsic disorder in the PA groups
      with either folded or unfolded apo-form using the average PONDR(r) VSL2P profiles
      revealed that the N-terminal region that includes alpha-helix A, AB-loop and N
      terminal half of alpha-helix B is predicted to be less ordered in PAs with
      disordered apo-state. Application of the structural criteria developed for
      discrimination of disordered PAs indicate that the latter comprise about 16-19%
      of all PAs. We show that structural instability of apo-beta-PA serves as a
      hallmark of elevated calcium affinity of the protein. Therefore, the successful
      predictions of unstable apo-PAs might facilitate search for PAs with maximal
      calcium affinity and possibly serving as calcium sensors.

PMID- 29029792
TI  - Analyzing optical imaging of Ca2+ signals via TIRF microscopy: The limits on
      resolution due to chemical rates and depth of the channels.
AB  - High resolution total internal reflection (TIRF) microscopy (TIRFM) together with
      detailed computational modeling provides a powerful approach towards the
      understanding of a wide range of Ca2+ signals mediated by the ubiquitous inositol
      1,4,5-trisphosphate (IP3) receptor (IP3R) channel. Exploiting this fruitful
      collaboration further requires close agreement between the models and
      observations. However, elementary Ca2+ release events, puffs, imaged through
      TIRFM do not show the rapid single-channel openings and closings during and
      between puffs as are present in simulated puffs using data-driven single channel
      models. TIRFM also shows a rapid equilibration of 10ms after a channel opens or
      closes which is not achievable in simulation using standard Ca2+ diffusion
      coefficients and reaction rates between indicator dye and Ca2+. Furthermore,
      TIRFM imaging cannot decipher the depth of the channel with respect to the
      microscope, which will affect the change in fluorescence that the microscope
      detects, thereby affecting its sensitivity to fast single-channel activity. Using
      the widely used Ca2+ diffusion coefficients and reaction rates, our simulations
      show equilibration rates that are eight times slower than TIRFM imaging. We show
      that to get equilibrium rates consistent with observed values, the diffusion
      coefficients and reaction rates have to be significantly higher than the values
      reported in the literature, and predict the channel depth to be 200-250nm.
      Finally, we show that with the addition of noise, short events due to 1-2ms
      opening and closing of channels that are observed in computational models can be
      missed in TIRFM.

PMID- 29029793
TI  - High extracellular Ca2+ enhances the adipocyte accumulation of bone marrow
      stromal cells through a decrease in cAMP.
AB  - Bone marrow stromal cells (BMSCs) are common progenitors of both adipocytes and
      osteoblasts. We recently suggested that increased [Ca2+]o caused by bone
      resorption might accelerate adipocyte accumulation in response to treatment with
      both insulin and dexamethasone. In this study, we investigated the mechanism by
      which high [Ca2+]o enhances adipocyte accumulation. We used primary mouse BMSCs
      and evaluated the levels of adipocyte accumulation by measuring Oil Red O
      staining. CaSR agonists (both Ca2+ and Sr2+) enhanced the accumulation of
      adipocytes among BMSCs in response to treatment with both insulin and
      dexamethasone. We showed that high [Ca2+]o decreases the concentration of cAMP
      using ELISA. Real-time RT-PCR revealed that increasing the intracellular
      concentration of cAMP (both chemical inducer (1MUM forskolin and 200nM IBMX) and
      a cAMP analog (10MUM pCPT-cAMP)) suppressed the expression of PPARgamma and
      C/EBPalpha. In addition, forskolin, IBMX, and pCPT-cAMP inhibited the enhancement
      in adipocyte accumulation under high [Ca2+]o in BMSCs. However, this inhibited
      effect was not observed in BMSCs that were cultured in a basal concentration of
      [Ca2+]o. We next observed that the accumulation of adipocytes in the of bone
      marrow of middle-aged mice (25-40 weeks old) is higher than that of young mice (6
      weeks old) based on micro CT. ELISA results revealed that the concentration of
      cAMP in the bone marrow mononuclear cells of middle-aged mice is lower than that
      of young mice. These data suggest that increased [Ca2+]o caused by bone
      resorption might accelerate adipocyte accumulation through CaSR following a
      decrease in cAMP.

PMID- 29029795
TI  - Autonomous health management for PMSM rail vehicles through demagnetization
      monitoring and prognosis control.
AB  - Autonomous vehicles are playing an increasingly importance in support of a wide
      variety of critical events. This paper presents a novel autonomous health
      management scheme on rail vehicles driven by permanent magnet synchronous motors
      (PMSMs). Firstly, the PMSMs are modeled based on first principle to deduce the
      initial profile of pneumatic braking (p-braking) force, then which is utilized
      for real-time demagnetization monitoring and degradation prognosis through
      similarity-based theory and generate prognosis-enhanced p-braking force strategy
      for final optimal control. A case study is conducted to demonstrate the
      feasibility and benefit of using the real-time prognostics and health management
      (PHM) information in vehicle 'drive-brake' control automatically. The results
      show that accurate demagnetization monitoring, degradation prognosis, and real
      time capability for control optimization can be obtained, which can effectively
      relieve brake shoe wear.

PMID- 29029796
TI  - Robust cubature Kalman filter for GNSS/INS with missing observations and colored
      measurement noise.
AB  - In order to improve the accuracy of GNSS/INS working in GNSS-denied environment,
      a robust cubature Kalman filter (RCKF) is developed by considering colored
      measurement noise and missing observations. First, an improved cubature Kalman
      filter (CKF) is derived by considering colored measurement noise, where the time
      differencing approach is applied to yield new observations. Then, after analyzing
      the disadvantages of existing methods, the measurement augment in processing
      colored noise is translated into processing the uncertainties of CKF, and new
      sigma point update framework is utilized to account for the bounded model
      uncertainties. By reusing the diffused sigma points and approximation residual in
      the prediction stage of CKF, the RCKF is developed and its error performance is
      analyzed theoretically. Results of numerical experiment and field test reveal
      that RCKF is more robust than CKF and extended Kalman filter (EKF), and compared
      with EKF, the heading error of land vehicle is reduced by about 72.4%.

PMID- 29029794
TI  - Rho-kinase inhibition reverses impaired Ca2+ handling and associated left
      ventricular dysfunction in pressure overload-induced cardiac hypertrophy.
AB  - Recent studies have implicated a relationship between RhoA/ROCK activity and
      defective Ca2+ homeostasis in hypertrophic hearts. This study investigated
      molecular mechanism underlying ROCK inhibition-mediated cardioprotection against
      pressure overload-induced cardiac hypertrophy, with a focus on Ca2+ homeostasis.
      Cardiac hypertrophy model was established by performing transverse aortic
      constriction (TAC) in 8-week-old male rats. Groups were assigned as SHAM, TAC and
      TAC+Fas (rats undergoing TAC and treated with fasudil). Rats in the TAC+Fas group
      were administered fasudil (5mg/kg/day), and rats in the SHAM and TAC groups were
      treated with vehicle for 10 weeks. Electrophysiological recordings were obtained
      from isolated left ventricular myocytes and expression levels of proteins were
      determined using western blotting. Rats in the TAC group showed remarkable
      cardiac hypertrophy, and fasudil treatment significantly reversed this
      alteration. TAC+Fas myocytes showed significant improvement in reduced
      contractility and Ca2+ transients. Moreover, these myocytes showed restoration of
      slow relaxation rate and Ca2+ reuptake. Although L-type Ca2+ currents did not
      change in TAC group, there was a significant reduction in the triggered Ca2+
      transients which was reversed either by long-term fasudil treatment or incubation
      of TAC myocytes with fasudil. The hearts of rats in the TAC group showed a
      significant decrease in ROCK1, ROCK2, RyR2 protein levels and p-PLBS16/T17/SERCA2
      ratio and increase in RhoA expression and MLC phosphorylation. However, fasudil
      treatment largely reversed TAC-induced alterations in protein expression. Thus,
      our findings indicate that upregulation of the RhoA/ROCK pathway is significantly
      associated with cardiac hypertrophy-related Ca2+ dysregulation and suggest that
      ROCK inhibition prevents hypertrophic heart failure.

PMID- 29029798
TI  - Effect of intravenous ondansetron on QTc interval in children with
      gastroenteritis.
AB  - BACKGROUND: The potential for ondansetron to cause QT prolongation and fatal
      dysrhythmia is well-reported, including a 2011 FDA report on the topic. Few
      clinical trials evaluating this phenomenon in the ED setting exist, and only one
      is pediatric. OBJECTIVE: We have sought to determine the effect of a standardized
      dose of intravenous ondansetron on the QTc duration of children under 14years of
      age treated for gastroenteritis-associated vomiting in a pediatric ED. This study
      is modeled closely after an FDA "thorough QT study". METHODS: EGCs were obtained
      before and 15, 30, 45, and 60min after a 0.15mg/kg IV dose of ondansetron given
      for gastroenteritis-associated vomiting. QT intervals were measured manually with
      digital calipers, and the QTc interval calculated both by Bazett's (QTcB) and
      Fridericia's (QTcF) correction. A paired t-test comparing QTc was conducted, and
      frequency of categorical outcomes of prolongation>30msec, >60 msec, and absolute
      prolongation >450 msec, >480 msec, and >500msec were evaluated. RESULTS: In a 4
      month period, 134 patients were included in the study, 46% were male. The average
      QTc prior to ondansetron administration was: QTcB 415 msec (95% CI 343-565) and
      QTcF 373 (95% CI 304-499). The mean difference in QTc after ondansetron was
      0.4msec for QTcB (95% CI -35-45msec) and 0.1msec for QTcF (95% CI -40-18msec).
      CONCLUSION: In these children, 0.15mg/kg of intravenous ondansetron did not cause
      prolongation of QTcB or QTcF measured 15min after administration, nor at later
      times.

PMID- 29029797
TI  - Comparison of IV dexketoprofen trometamol, fentanyl, and paracetamol in the
      treatment of renal colic in the ED: A randomized controlled trial.
AB  - OBJECTIVE: In this study, we aimed to compare the analgesic efficacy of
      intravenous dexketoprofen trometamol, fentanyl, and paracetamol in patients
      presenting to the emergency department with renal colic. MATERIALS AND METHOD:
      Data obtained from the emergency departments of Gaziantep University's Hospital
      for Research and Practice along with two other state hospitals in Gaziantep,
      Turkey between January 2016 and January 2017 was used for this study. A total of
      three hundred patients (n=300), who presented to the ER with complaints most
      common to renal colic whose diagnoses were subsequently confirmed with
      Computerized Tomography were included in the study. Patients' pain scores were
      recorded using the Visual Analogue Scale, at admission (immediately before drug
      administration), then at the 15th, and 30th minutes. SPSS 22.0 software package
      was used for analysis. p<0.05 was considered significant. RESULTS: At the 15th
      minute comparison, the efficacies of the three groups of drugs were not superior
      to one other, but at the 30th minute, dexketoprofen trometamol was statistically
      more effective than paracetamol and fentanyl. There was no statistically
      significant difference between fentanyl and paracetamol. The need for additional
      analgesia in the group receiving dexketoprofen trometamol was found to be lower.
      Dexketoprofen trometamol was statistically superior to the other two agents in
      achieving full analgesia at the end of the thirty-minute period. Fentanyl was
      found to be statistically significant in achieving moderate analgesia.
      CONCLUSION: As a Non-steroidal antiinflammatory drug dexketoprofen trometamol is
      superior to paracetamol and fentanyl in achieving analgesia and reducing the need
      for additional drugs for the treatment of renal colic.

PMID- 29029799
TI  - Interdependent and independent multidimensional role of tumor microenvironment on
      hepatocellular carcinoma.
AB  - The novelty of an effective therapeutic targeting for hepatocellular carcinoma
      (HCC) is based on improved understanding of each component of tumor
      microenvironment (TME) and its correspondent interactions at biological and
      molecular levels. In this context, new expansions for the treatment against TME
      and its communication with HCC are under exploration. Despite of the fact that
      blockage of growth factor receptors has become a treatment of choice in late
      phases of HCC in clinical practice, still a precise targeted treatment should
      address all the components of TME. Targeting one specific element out of cellular
      (cancer associated fibroblasts, endothelial cells, hepatic stellate cells,
      Kupffer cells and lymphocytes) or non-cellular (extracellular matrix, growth
      factors, inflammatory cytokines, proteolytic enzymes) parts of TME may not be a
      successful remedy for the disease because of well-designed hindrances of each
      component and their functional alternativeness. Meanwhile there are some elements
      of TME like epithelial-mesenchymal transition and CAF, which are considerably
      important and need thorough investigations. Ascertaining the potential role of
      these elements, and a single or combinational drug therapy targeting these
      elements of TME simultaneously, may provide the appreciable considerations to
      eventually improve in clinical practices and may also minimize the chances of
      reoccurrence of HCC.

PMID- 29029800
TI  - Surgical treatment of neuronal-glial tumors of mesial-basal part of temporal
      lobe: Long term outcome and control of epilepsy in pediatric patients.
AB  - BACKGROUND: Neuronal-glial tumors (ganglioglioma and dysembryoplastic
      neuroepithelial tumor) are a frequent cause of focal, drug-resistant and epilepsy
      in children and young adults, that is amenable for surgical treatment. AIM OF
      PAPER: Assessment of late outcome of surgical treatment and degree of seizure
      control, as well as prognostic significance of selected clinical factors.
      MATERIAL AND METHOD: 52 Pediatric patients presenting with epilepsy, lesion of
      mesio-basal temporal lobe and histologically verified neuronal-glial tumor
      treated at our facility since 2000-2011. RESULTS: After the mean follow-up of
      2.94 years, satisfactory treatment outcome (Engel classes I and II) was obtained
      in 92% of the patients (n=48). Poor outcome (Engel class III) was seen in 8% of
      patients (n=4). New neurological deficits appeared in 28% of the patients (n=20)
      but in most of them resolved over time. CONCLUSIONS: In patients with drug
      resistant epilepsy and a lesion of mesial-basal part of temporal lobe suggestive
      of a glial-neuronal tumor, surgical treatment is strongly recommended, aiming at
      excision of tumor and elimination of seizures. Histological verification of the
      lesion is a pre-requisite for optimal treatment planning. In most patients, both
      treatment goals may be reached. Short duration of epilepsy prior to surgery and
      young age are favorable prognostic factors. Histological diagnosis of GG, co
      existence of cortical dysplasia and location of tumor extending beyond mesial
      basal temporal structures are associated with a higher risk of postoperative
      complications. These may out-weight expected benefits of surgery.

PMID- 29029801
TI  - Throwing out the good with the bad: Declining potential donor hearts with left
      ventricular dysfunction.

PMID- 29029803
TI  - Introduction to the special issue 'unintended effects of international
      cooperation'.
AB  - The 'Evaluation and Program Planning' journal has contributed to the launch of an
      academic discussion of unintended effects of international cooperation, notably
      by publishing in 2016 articles by Bamberger, Tarsilla, & Hesse-Biber and by
      Jabeen. This special issue aims to take up the academic challenges as laid down
      by those authors, by providing among others a clear typology and applying it, by
      outlining various methodological options and testing them, and elaborating on
      suggestions on how to deal with the barriers that prevent unintended effects
      being taken into account. This special issue makes clear that it is possible to
      reduce the share of unforeseen effects of international cooperation. Turning the
      spotlight on unintended effects that can be anticipated, and aiming to make
      progress on uncovering those that are particularly difficult to detect and
      debunking those that are exaggerated is the task that lies ahead of us.

PMID- 29029802
TI  - Early-life environmental exposures interact with genetic susceptibility variants
      in pediatric patients with eosinophilic esophagitis.
AB  - BACKGROUND: Although eosinophilic esophagitis (EoE) is associated with certain
      gene variants, the rapidly increasing incidence of EoE suggests that
      environmental factors contribute to disease development. OBJECTIVE: We tested for
      gene-environment interaction between EoE-predisposing polymorphisms (within TSLP,
      LOC283710/KLF13, CAPN14, CCL26, and TGFB) and implicated early-life factors
      (antibiotic use in infancy, cesarean delivery, breast-feeding, neonatal intensive
      care unit [NICU] admission, and absence of pets in the home). METHODS: We
      conducted a case-control study using hospital-based cases (n = 127) and control
      subjects representative of the hospital catchment area (n = 121). We computed
      case-only interaction tests and in secondary analyses evaluated the combined and
      independent effects of genotype and environmental factors on the risk of EoE.
      RESULTS: Case-only analyses identified interactions between rs6736278 (CAPN14)
      and breast-feeding (P = .02) and rs17815905 (LOC283710/KLF13) and NICU admission
      (P = .02) but not with any of the factors examined. Case-control analyses
      suggested that disease risk might be modifiable in subjects with certain gene
      variants. In particular, breast-feeding in those with the susceptibility gene
      variant at rs6736278 (CAPN14) reduced the risk of EoE (adjusted odds ratio, 0.08;
      95% CI, 0.01-0.59). Admission to the NICU in those without the susceptibility
      gene variant at rs17815905 (LOC283710/KLF13) significantly increased the risk of
      having disease (adjusted odds ratio, 4.83; 95% CI, 1.49-15.66). CONCLUSIONS: The
      interplay of gene (CAPN14 and LOC283710/KLF13) and early-life environment factors
      (breast-feeding and NICU admission) might contribute to EoE susceptibility.

PMID- 29029804
TI  - A weight-of-evidence approach for the bioaccumulation assessment of triclosan in
      aquatic species.
AB  - The bioaccumulation assessment of chemicals is challenging because of various
      metrics and criteria, multiple lines of evidence and underlying uncertainty in
      the data. Measured in vivo laboratory and field bioaccumulation data are
      generally considered preferable; however, quantitative structure-activity
      relationships (QSARs), mass balance models and in vitro data can also be
      considered. This case study critically evaluates in vivo, in vitro and in silico
      data and provides new data for the bioaccumulation assessment of triclosan (TCS).
      The review focusses on measured fish bioconcentration factors (BCFs) because this
      is the most commonly used regulatory metric. Reported measured fish BCFs range
      from about 20 to 8700L/kg-ww spanning a range of possible bioaccumulation
      assessment outcomes, i.e. from "not bioaccumulative" to "very bioaccumulative".
      Estimated biotransformation rate constants for fish obtained from in vivo, in
      vitro and in silico methods show general consensus fostering confidence in the
      selection of plausible values to confront uncertainty in the measured fish BCF
      tests. Other measurements (lines of evidence) from various species are also
      collected and reviewed. The estimated biotransformation rate constants and
      selected chemical property data are used to parameterize bioaccumulation models
      for aquatic species. Collectively the available lines of evidence are presented
      using a weight of evidence approach for assessing the bioaccumulation of TCS in
      aquatic species. Acceptable quality measured data and model predictions for TCS
      BCFs and bioaccumulation factors are lower than 2000L/kg. Biomagnification
      factors are <1 (kg/kg). The general consistency in the acceptable quality data is
      largely explained by the relatively efficient rates of TCS biotransformation in a
      range of species including measurements of significant in vitro activity of phase
      II conjugation reactions. The review demonstrates the value of combining models
      and measurements and, when necessary, applying multiple lines of evidence for
      chemical assessment.

PMID- 29029805
TI  - Glycan diversity in the vomeronasal organ of the Korean roe deer, Capreolus
      pygargus: A lectin histochemical study.
AB  - Glycans in the epithelium play an important role in cell-to-cell communication
      and adhesion. No detailed evaluation of glycoconjugates in the vomeronasal organs
      (VNO) of the roe deer has been published previously. The aim of this study was to
      characterize glycan epitopes in the vomeronasal sensory epithelium (VSE) and non
      sensory epithelium (VNSE) using lectin histochemistry. Glycan epitopes identified
      by lectin histochemistry were grouped as follows: N-acetylglucosamine (s-WGA,
      WGA, BSL-II, DSL, LEL, STL), mannose (Con A, LCA, PSA), galactose (RCA120, BSL-I,
      Jacalin, PNA, ECL), N-acetylgalactosamine (VVA, DBA, SBA, and SJA), fucose (UEA
      I) and complex type N-glycan (PHA-E and PHA-L) groups. The free border of the VSE
      was positive for all 21 lectins, and 18 of the lectins (excluding DBA, SJA, and
      PHA-L) showed weak and/or moderate staining in the receptor cells. The supporting
      cells were weakly positive for 19 lectins (excluding PNA and SJA). Moreover, 17
      lectins (excluding BSL-II, Jacalin, PNA, and SJA) were expressed in the basal
      cells. In the VNSE of roe deer, the free border showed staining for all 21
      lectins examined. The ciliated cells were positive for 16 lectins (excluding BSL
      II, DSL, PNA, VVA, and SJA). Furthermore, 15 lectins (excluding DSL, LEL, ECL,
      UEA-I, PHA-E, and PHA-L) were expressed in goblet cells. Twenty lectins
      (excluding SJA) were expressed in the acini of the vomeronasal glands.
      Collectively, both VSE and VNSE were rich in N-acetylglucosamine, mannose,
      galactose, N-acetylgalactosamine, fucose, and complex-type N-glycans, although
      the different cell types of the VSE and VNSE expressed different glycoconjugates
      of varying intensities, suggesting that these carbohydrate residues may be
      involved in odor perception as well as cell-to-cell communication in the VNO.

PMID- 29029806
TI  - "Mojito's" phytophotodermatitis, the other "lime" disease.

PMID- 29029807
TI  - Binding and neutralizing anti-cytomegalovirus activities in immune globulin
      products.
AB  - Congenital infection as well as infection of immunocompromised individuals by
      cytomegalovirus (CMV) can be associated with significant morbidity, mortality,
      and long-term adverse health outcomes. Assessment of anti-viral activity using
      appropriate assays is essential for ensuring safe and efficacious use of
      therapeutic CMV immune globulin (IG) products. In this study, we used commercial
      ELISA kits to compare anti-CMV antibody binding activity and avidity for lots of
      CMV-specific and normal IG products available in the US market. Additionally,
      neutralizing activity of IG products was measured against CMV strains (AD169wt131
      or TB40E-GFP) in MRC-5 human fibroblasts and ARPE-19 human epithelial cells. Our
      data revealed that, regardless of the method, anti-CMV activity was higher in CMV
      IG lots we tested compared with normal IG lots; CMV binding activity was at least
      4-fold higher, and neutralizing activity at least 2- and 3-fold higher for
      epithelial and fibroblast cells, respectively, in CMV IG lots compared with
      normal IG lots. Furthermore, anti-CMV activity values from all three methods
      (ELISA, neutralization in MRC-5 cells, and neutralization in ARPE-19 cells) were
      highly correlated, whereas avidity, although higher in CMV IG lots, did not
      correlate well with either binding or neutralizing activities.

PMID- 29029809
TI  - Reply to "Comment on "Ecological niche of Neanderthals from Spy Cave revealed by
      nitrogen isotopes of individual amino acids in collagen." [J. Hum. Evol. 93
      (2016) 82-90]" [J. Hum. Evol. 117 (2018) 53-55].

PMID- 29029808
TI  - Potassium Homeostasis in Health and Disease: A Scientific Workshop Cosponsored by
      the National Kidney Foundation and the American Society of Hypertension.
AB  - While much emphasis, and some controversy, centers on recommendations for sodium
      intake, there has been considerably less interest in recommendations for dietary
      potassium intake, in both the general population and patients with medical
      conditions, particularly acute and chronic kidney disease. Physiology literature
      and cohort studies have noted that the relative balance in sodium and potassium
      intakes is an important determinant of many of the sodium-related outcomes. A
      noteworthy characteristic of potassium in clinical medicine is the extreme
      concern shared by many practitioners when confronted by a patient with
      hyperkalemia. Fear of this often asymptomatic finding limits enthusiasm for
      recommending potassium intake and often limits the use of renin-angiotensin
      aldosterone system blockers in patients with heart failure and chronic kidney
      diseases. New agents for managing hyperkalemia may alter the long-term management
      of heart failure and the hypertension, proteinuria, and further function loss in
      chronic kidney diseases. In this jointly sponsored effort between the American
      Society of Hypertension and the National Kidney Foundation, 3 panels of
      researchers and practitioners from various disciplines discussed and summarized
      current understanding of the role of potassium in health and disease, focusing on
      cardiovascular, nutritional, and kidney considerations associated with both hypo-
      and hyperkalemia.

PMID- 29029810
TI  - Characteristics and Changes of Pediatric Therapeutic Trials under the Best
      Pharmaceuticals for Children Act.

PMID- 29029812
TI  - Child survival in England: Strengthening governance for health.
AB  - The United Kingdom, like all European countries, is struggling to strengthen
      health systems and improve conditions for child health and survival. Child
      mortality in the UK has failed to improve in line with other countries. Securing
      optimal conditions for child health requires a healthy society, strong health
      system, and effective health care. We examine inter-sectoral and intra-sectoral
      policy and governance for child health and survival in England. Literature
      reviews and universally applicable clinical scenarios were used to examine child
      health problems and English policy and governance responses for improving child
      health through integrating care and strengthening health systems, over the past
      15 years. We applied the TAPIC framework for analysing policy governance:
      transparency, accountability, participation, integrity, and capacity. We
      identified strengths and weaknesses in child health governance in all the five
      domains. However there remain policy failures that are not fully explained by the
      TAPIC framework. Other problems with successfully translating policy to improved
      health that we identified include policy flux; policies insufficiently supported
      by delivery mechanisms, measurable targets, and sufficient budgets; and policies
      with unintended or contradictory aspects. We make recommendations for inter
      sectoral and intra-sectoral child health governance, policy, and action to
      improve child health in England with relevant lessons for other countries.

PMID- 29029811
TI  - How has the management of acute coronary syndrome changed in the Russian
      Federation during the last 10 years?
AB  - METHODS: We report trends and patterns of percutaneous cardiovascular
      interventions (PCI) by region for 2005-2009, with more detailed data on
      management of myocardial infarctions in 2009-2103, relating them to regional
      economic development and changes in mortality from myocardial infarction.
      RESULTS: PCIs per 100,000 population increased from 8.7 in 2005-71.3 in 2013,
      with considerable regional variation. In 2013 the highest rates were in the
      wealthiest regions, although not in some remote regions dependent on oil and
      mineral extraction. Between 2009 and 2013 rates of thrombolysis in those with
      acute myocardial infarctions potentially eligible for treatment remained broadly
      similar at about 28% but rates of primary revascularisation with stenting rose
      rapidly, from 6.5% to 23.7%. In-hospital mortality from myocardial infarction
      since 2009 has declined most in regions achieving highest rates of primary
      revascularisation. CONCLUSIONS: The sustained investment in advanced
      cardiovascular technology has been associated with substantial increases in
      revascularisation in some but not all regions. However, rates overall remain far
      behind those in Western Europe. Further research is in progress to understand the
      reasons for these variations and the barriers to further expansion of services.

PMID- 29029813
TI  - Innovative Therapy, Monoclonal Antibodies and Beyond.
AB  - The seventh Edition of "Innovative Therapy, Monoclonal Antibodies and Beyond"
      Meeting took place in Milan, Italy, on January 27, 2017. The two sessions of the
      meeting were focused on: 1) Preclinical assays and novel biotargets; and 2)
      monoclonal antibodies, cell therapies and targeted molecules. Between these two
      sessions, a lecture entitled "HLA-antigens modulation and response to immune
      checkpoint inhibitor immunotherapy" was also presented. Despite the impressive
      successes in cancer immunotherapy in recent years, the response to immune based
      interventions occurs only in a minority of patients (~20%). Several basic and
      translational mechanisms of resistance to immune checkpoint blockers (ICBs) were
      discussed during the meeting: 1. the impact of tumor microenvironment on the
      activity of immune system; 2. strategies to inhibit the cross-talk between
      extracellular matrix and myeloid-derived suppressor cells (MDSC) in the
      preclinical setting; 3. microRNA expression as a biomarker and as a target of
      therapy in non-small cell lung cancer (NSCLC); 4. the significance of complement
      activation pathways in response to immune checkpoint inhibitors; 5. the
      immunosuppressive activity of the microbiota by inducing IL-17 producing cells;
      and 6. modulation of HLA antigens as possible markers of response to ICB therapy.
      In order to overcome the deficiency in active anti-tumor T cells, several
      clinically applicable combination strategies were also discussed: 1. strategies
      to enhance the anticancer effects of immunogenic cell death inducing
      chemotherapy; 2. the use of CAR T-cells in solid tumors; 3. the use of
      combination strategies involving oncolytic viruses and ICBs; 4. combinations of
      new ICBs with anti-PD-1/CTLA-4 therapy; and 4. combinations of targeted therapies
      and ICBs in melanoma. Overall, this conference emphasized the many novel
      strategies that are being investigated to improve the overall patient response to
      cancer immunotherapy. Optimization of biomarkers to accurately select patients
      who will respond to immunotherapy, coupled with combination strategies to improve
      long term patient survival remain critical challenges in the immuno-oncology
      field.

PMID- 29029814
TI  - Systematic review of electronic surveillance of infectious diseases with emphasis
      on antimicrobial resistance surveillance in resource-limited settings.
AB  - BACKGROUND: Electronic surveillance of infectious diseases involves rapidly
      collecting, collating, and analyzing vast amounts of data from interrelated
      multiple databases. Although many developed countries have invested in electronic
      surveillance for infectious diseases, the system still presents a challenge for
      resource-limited health care settings. METHODS: We conducted a systematic review
      by performing a comprehensive literature search on MEDLINE (January 2000-December
      2015) to identify studies relevant to electronic surveillance of infectious
      diseases. Study characteristics and results were extracted and systematically
      reviewed by 3 infectious disease physicians. RESULTS: A total of 110 studies were
      included. Most surveillance systems were developed and implemented in high-income
      countries; less than one-quarter were conducted in low-or middle-income
      countries. Information technologies can be used to facilitate the process of
      obtaining laboratory, clinical, and pharmacologic data for the surveillance of
      infectious diseases, including antimicrobial resistance (AMR) infections. These
      novel systems require greater resources; however, we found that using electronic
      surveillance systems could result in shorter times to detect targeted infectious
      diseases and improvement of data collection. CONCLUSIONS: This study highlights a
      lack of resources in areas where an effective, rapid surveillance system is most
      needed. The availability of information technology for the electronic
      surveillance of infectious diseases, including AMR infections, will facilitate
      the prevention and containment of such emerging infectious diseases.

PMID- 29029815
TI  - Induced effect of Ca2+ on dalesconols A and B biosynthesis in the culture of
      Daldinia eschscholzii via calcium/calmodulin signaling.
AB  - Dalesconols (dalesconols A and B) were isolated from Daldinia eschscholzii and
      have remarkable immunosuppressive activity. In this study, the response of fungal
      growth, intra- and extracellular Ca2+, and dalesconols production after CaCl2
      addition were reported for the first time. After supplementation with 5 mM Ca2+
      at 24 h, dalesconols production reached 84.33 mg/L, which resulted in a 1.57-fold
      enhancement compared to the control. The key role of calcium/calmodulin signaling
      in dalesconols biosynthesis was confirmed by treatment with Ca2+ channel and
      calmodulin inhibitors. The transcriptional levels of dalesconols biosynthetic
      genes were up-regulated after CaCl2 addition and down-regulated after inhibitors
      were added. The results demonstrated that Ca2+ addition induces dalesconols
      biosynthesis through up-regulation of dalesconols biosynthesis genes via
      regulation of calcium/calmodulin signaling. This study provided an efficient
      strategy for improving dalesconols production and would facilitate further
      research on the biosynthesis and regulation of dalesconols.

PMID- 29029817
TI  - Predictable or fateful-a short guide for how to anticipate risk to keep the
      incidence of aortoesophageal fistulation to a minimum.

PMID- 29029816
TI  - Functional analysis of methyltransferases participating in streptothricin-related
      antibiotic biosynthesis.
AB  - Streptothricin (ST) and its related compounds produced by Streptomyces strains
      are broad-spectrum antibiotics that consist of carbamoylated d-gulosamine, amino
      acid side chain, and streptolidine lactam moieties. BD-12, a streptothricin
      related antibiotic, has a glycine-derived side chain and two N-methyl groups,
      whereas ST-F carrying the l-beta-lysine side chain has no methyl group. In our
      previous studies, we identified and characterized the BD-12 and ST biosynthetic
      gene clusters. Here we report the functional analysis of two methyltransferase
      genes (orf 6 and orf 13) in the BD-12 biosynthetic gene cluster. Combinatorial
      biosynthesis using these two methyltransferase genes and the ST biosynthetic gene
      cluster resulted in the production of three methylated forms of ST-F. Among them,
      N,N'-dimethyl-ST-F, a novel compound generated in the present study, showed
      bacteria-specific antibiotic activities, although ST-F exhibits antibiotic
      activities against both prokaryotes and eukaryotes. Our findings also
      demonstrated that the orf 6 and orf 13 genes are responsible for the N
      methylations of the amide bonds in the streptolidine lactam and in the amino-acid
      side chain linkage, respectively, and that N-methyl modification of the
      streptolidine lactam confers resistance in part against an ST hydrolase, SttH.

PMID- 29029818
TI  - Anomalous aortic origin of a coronary artery: 90% of optimal therapy is 50%
      improved technology.

PMID- 29029819
TI  - The left internal thoracic artery supplying a major part of the gastrointestinal
      tract.

PMID- 29029820
TI  - To breathe or to breathe better: Is that the question?

PMID- 29029821
TI  - The thoracoabdominal saga and heroes.

PMID- 29029822
TI  - Which aortic valve prosthesis I would implant on myself?

PMID- 29029823
TI  - Open melody implant in a vascular graft-An alternative to the bioprosthetic
      valve?

PMID- 29029824
TI  - Increased cerebrospinal fluid levels of cytokines monocyte chemoattractant
      protein-1 (MCP-1) and macrophage inflammatory protein-1beta (MIP-1beta) in
      patients with amyotrophic lateral sclerosis.
AB  - INTRODUCTION: Neuroinflammation has recently been described in amyotrophic
      lateral sclerosis (ALS). However, the precise role of such proinflammatory
      cytokines as monocyte chemoattractant protein-1 (MCP-1) and macrophage
      inflammatory protein-1beta (MIP-1beta) in ALS has not yet been determined. In
      this study, we determined cerebrospinal fluid (CSF) MCP-1 and MIP-1beta levels
      and assessed their association with the duration and severity of ALS. METHODS:
      Concentrations of MCP-1 and MIP-1beta were determined in the CSF of 77 patients
      diagnosed with ALS and 13 controls. Cytokine levels were analysed in relation to
      ALS duration (<12months vs. >12months) and severity (<30points vs. >30points on
      the ALS Functional Rating Scale administered at hospital admission). RESULTS:
      Higher CSF MIP-1beta (10.68pg/mL vs. 4.69pg/mL, P<.0001) and MCP-1 (234.89pg/mL
      vs. 160.95pg/mL, P=.011) levels were found in the 77 patients with ALS compared
      to controls. There were no differences in levels of either cytokine in relation
      to disease duration or severity. However, we did observe a significant positive
      correlation between MIP-1beta and MCP-1 in patients with ALS. CONCLUSIONS: The
      increase in MIP-1beta and MCP-1 levels suggests that these cytokines may have a
      synergistic effect on ALS pathogenesis. However, in our cohort, no association
      was found with either the duration or the clinical severity of the disease.

PMID- 29029825
TI  - [Cherry red spot macula in the context of Tay-Sachs disease].

PMID- 29029826
TI  - [Fear the power of the fingers!]

PMID- 29029827
TI  - Dancing with the Stars: An Asterid NLR Family.
AB  - Wu and co-workers show how a network of sensor and helper NOD-like receptor
      proteins (NLRs) act together to confer robust resistance to diverse plant
      pathogens.

PMID- 29029828
TI  - Bridging Scales in Plant Biology Using Network Science.
AB  - Three recent studies have captured the organizational properties of plants at
      each the cellular, organ, and whole organism level. Data abstraction into
      networks enabled topological analyses to be performed, identifying optimizations
      within each scale. Multiscale network analysis provides the opportunity to
      integrate these levels, and quantitatively link genotype to phenotype.

PMID- 29029829
TI  - Oxygen, Energy, and Light Signalling Direct Meristem Fate.
AB  - Light, nutrition, and oxygen are each important cues for developmental
      transitions in plants. A small number of recent studies have converged to give
      the first indication of how these environmental cues act together and
      independently via auxin, cytokinin, and ethylene to regulate cell proliferation
      in the root and shoot meristems.

PMID- 29029830
TI  - Responsiveness of Persian Version of Consensus Auditory Perceptual Evaluation of
      Voice (CAPE-V), Persian Version of Voice Handicap Index (VHI), and Praat in Vocal
      Mass Lesions with Muscle Tension Dysphonia.
AB  - OBJECTIVES: This study was aimed at determining the internal and external
      responsiveness of the Persian version of the Consensus Auditory-Perceptual
      Evaluation of Voice (called ATSHA), Persian version of the Voice Handicap Index
      (VHI), and Praat scales among patients with vocal mass lesions and secondary
      muscle tension dysphonia. STUDY DESIGN: Prospective, within-participant repeated
      measures. METHOD: Thirty patients with vocal fold nodules, polyps, and cysts
      related to secondary muscle tension dysphonia participated in the study. The
      measures of interest and videostroboscopy examination were used before and after
      treatment. The Global Perceived Effect questionnaire was used to separate those
      improved (moderately or greatly improved) and stable (slightly improved)
      patients. RESULTS: The mean standardized response, standardized effect size, and
      Guyatt analyses indicated high internal responsiveness for the all target
      parameters of the ATSHA, total score of the VHI, and two parameters of the Praat
      (0.8<). There was poor correlation between the videostroboscopy and the other
      target scales (r Pearson = -0.1-0.1). The receiver operating characteristic
      analysis indicated that all the target scales did not significantly separate
      those improved and stable subjects (area under the curve = 0), except for the
      overall severity and roughness parameters of the ATSHA scale (area under the
      curve = 1). CONCLUSION: This study recommends both the Consensus Auditory
      Perceptual Evaluation of Voice and the VHI scales to show voice therapy changes.
      The target voice scale changes were not able to predict the videostroboscopy
      changes as external standard. Furthermore, we recommend that the overall severity
      and roughness may properly classify those improved and stable patients.

PMID- 29029831
TI  - Transmission Electron Microscopy of the Presbylarynx in the Process of Voice
      Aging.
AB  - INTRODUCTION: Microscopy studies of presbylarynx have identified epithelial
      atrophy, as well as vocal muscle atrophy, increased collagen, and decreased
      nonfibrous proteins of the extracellular matrix. Studies on the ultrastructure of
      presbylarynx are rare and can help us understand the pathophysiology of
      presbyphonia. OBJECTIVE: To describe details on the ultrastructure of
      presbylarynx by transmission electron microscopy (TEM). SUBJECTS AND METHODS:
      Sixteen human larynges were removed and distributed in two groups: control (n =
      8; 30-50 years; six females, two males) and seniors (n = 8; 75-92 years; six
      females, two males). After preparation for TEM, the specimens, including
      epithelium and lamina propria, were examined and photographed at increasing
      magnification. RESULTS: Control: the epithelium was intact, with overlapped
      cells, and with desmosomes between the intercellular junctions. The basement
      membrane was continuous and uniform, and the lamina propria contained collagen
      and elastic fibers in a regularly distributed loose arrangement, as well as some
      fibroblasts of different shapes. Senior: the epithelial cells were separated by
      enlarged intercellular junctions. The basement membrane was delicate and
      continuous. In the lamina propria there was predominance of elongated
      fibroblasts. Under the basement membrane a dense network of collagen fibers could
      be identified. CONCLUSIONS: In this study with TEM some structural changes were
      identified, particularly in the larynx of the elderly, both in the epithelium and
      lamina propria, some of them with likely participation of fibroblasts, which
      reinforces the importance of additional ultrastructure as well as molecular
      studies targeting those cells, as they are the main precursors of the components
      of the extracellular matrix.

PMID- 29029832
TI  - Tumour auto-contouring on 2d cine MRI for locally advanced lung cancer: A
      comparative study.
AB  - BACKGROUND AND PURPOSE: Radiotherapy guidance based on magnetic resonance imaging
      (MRI) is currently becoming a clinical reality. Fast 2d cine MRI sequences are
      expected to increase the precision of radiation delivery by facilitating tumour
      delineation during treatment. This study compares four auto-contouring algorithms
      for the task of delineating the primary tumour in six locally advanced (LA) lung
      cancer patients. MATERIAL AND METHODS: Twenty-two cine MRI sequences were
      acquired using either a balanced steady-state free precession or a spoiled
      gradient echo imaging technique. Contours derived by the auto-contouring
      algorithms were compared against manual reference contours. A selection of eight
      image data sets was also used to assess the inter-observer delineation
      uncertainty. RESULTS: Algorithmically derived contours agreed well with the
      manual reference contours (median Dice similarity index: ?0.91). Multi-template
      matching and deformable image registration performed significantly better than
      feature-driven registration and the pulse-coupled neural network (PCNN). Neither
      MRI sequence nor image orientation was a conclusive predictor for algorithmic
      performance. Motion significantly degraded the performance of the PCNN. The inter
      observer variability was of the same order of magnitude as the algorithmic
      performance. CONCLUSION: Auto-contouring of tumours on cine MRI is feasible in LA
      lung cancer patients. Despite large variations in implementation complexity, the
      different algorithms all have relatively similar performance.

PMID- 29029833
TI  - Interim 18F-FDG-PET/CT during chemo-radiotherapy in the management of oesophageal
      cancer patients. A systematic review.
AB  - Oesophageal cancer is an aggressive disease. The possibility to early stratify
      patients as responsive and non-responsive with a non-invasive method is extremely
      appealing. The uptake of Fluorodeoxyglucose (18F-FDG) in tumours, provided by
      positron emission tomography (PET) images, has been proved to be useful to assess
      the initial staging of the disease, recurrence, and response to chemotherapy and
      chemo-radiotherapy (CRT). In the last years, efforts have been focused on the
      possibility to use ad interim 18F-FDG-PET/CT (PETint) to evaluate response during
      radiation therapy. However, controversial findings have been reported, although
      some relevant results would support its use for individual therapeutic decision.
      The present review assembles the comprehensive literature of the last decade to
      evaluate whether and in which cases PETint may offer predictive potential in
      oesophageal cancer. All the analysed studies (13 studies, 697 patients) denoted
      PETint as a challenging examination for early assessment of outcomes during CRT.
      In particular, 8 studies advocated the predictivity of PETint, whilst 5 did not
      find any correlation between the interim variation of PET parameters and the
      pathological complete response and/or the clinical outcome. The reasons that
      possibly have caused contradictions among the studies demand further research
      with prospective and uniform protocols and methods of analysis to assess the
      predictive and prognostic value of PETint in oesophageal cancer.

PMID- 29029834
TI  - Biochar composite membrane for high performance pollutant management:
      Fabrication, structural characteristics and synergistic mechanisms.
AB  - Biochar, a natural sourced carbon-rich material, has been used commonly in
      particle shape for carbon sequestration, soil fertility and environmental
      remediation. Here, we report a facile approach to fabricate freestanding biochar
      composite membranes for the first time. Wood biochars pyrolyzed at 300  degrees C
      and 700  degrees C were blended with polyvinylidene fluoride (PVdF) in three
      percentages (10%, 30% and 50%) to construct membranes through thermal phase
      inversion process. The resultant biochar composite membranes possess high
      mechanical strength and porous structure with uniform distribution of biochar
      particles throughout the membrane surface and cross-section. The membrane pure
      water flux was increased with B300 content (4825-5411 +/- 21 L m-2 h-1) and B700
      content (5823-6895 +/- 72 L m-2 h-1). The membranes with B300 were more
      hydrophilic with higher surface free energy (58.84-60.31 mJ m-2) in comparison to
      B700 (56.32-51.91 mJ m-2). The biochar composite membranes indicated promising
      adsorption capacities (47-187 mg g-1) to Rhodamine B (RhB) dye. The biochar
      membranes also exhibited high retention (74-93%) for E. coli bacterial
      suspensions through filtration. After simple physical cleaning, both the
      adsorption and sieving capabilities of the biochar composite membranes could be
      effectively recovered. Synergistic mechanisms of biochar/PVdF in the composite
      membrane are proposed to elucidate the high performance of the membrane in
      pollutant management. The multifunctional biochar composite membrane not only
      effectively prevent the problems caused by directly using biochar particle as
      sorbent but also can be produced in large scale, indicating great potential for
      practical applications.

PMID- 29029835
TI  - Large-scale multi-stage constructed wetlands for secondary effluents treatment in
      northern China: Carbon dynamics.
AB  - Multi-stage constructed wetlands (CWs) have been proved to be a cost-effective
      alternative in the treatment of various wastewaters for improving the treatment
      performance as compared with the conventional single-stage CWs. However, few long
      term full-scale multi-stage CWs have been performed and evaluated for polishing
      effluents from domestic wastewater treatment plants (WWTP). This study
      investigated the seasonal and spatial dynamics of carbon and the effects of the
      key factors (input loading and temperature) in the large-scale seven-stage Wu
      River CW polishing domestic WWTP effluents in northern China. The results
      indicated a significant improvement in water quality. Significant seasonal and
      spatial variations of organics removal were observed in the Wu River CW with a
      higher COD removal efficiency of 64-66% in summer and fall. Obvious seasonal and
      spatial variations of CH4 and CO2 emissions were also found with the average CH4
      and CO2 emission rates of 3.78-35.54 mg m-2 d-1 and 610.78-8992.71 mg m-2 d-1,
      respectively, while the higher CH4 and CO2 emission flux was obtained in spring
      and summer. Seasonal air temperatures and inflow COD loading rates significantly
      affected organics removal and CH4 emission, but they appeared to have a weak
      influence on CO2 emission. Overall, this study suggested that large-scale Wu
      River CW might be a potential source of GHG, but considering the sustainability
      of the multi-stage CW, the inflow COD loading rate of 1.8-2.0 g m-2 d-1 and
      temperature of 15-20  degrees C may be the suitable condition for achieving the
      higher organics removal efficiency and lower greenhouse gases (GHG) emission in
      polishing the domestic WWTP effluent. The obtained knowledge of the carbon
      dynamics in large-scale Wu River CW will be helpful for understanding the carbon
      cycles, but also can provide useful field experience for the design, operation
      and management of multi-stage CW treatments.

PMID- 29029836
TI  - Uranium in agricultural soils and drinking water wells on the Swiss Plateau.
AB  - Mineral phosphorus fertilizers are regularly applied to agricultural sites, but
      their uranium (U) content is potentially hazardous to humans and the environment.
      Fertilizer-derived U can accumulate in the soil, but might also leach to ground-,
      spring and surface waters. We sampled 19 mineral fertilizers from the canton of
      Bern and soils of three arable and one forest reference sites at each of four
      locations with elevated U concentrations (7-28 MUg L-1) in nearby drinking water
      wells. The total U concentrations of the fertilizers were measured. The soils
      were analysed at three depth intervals down to 1 m for general soil parameters,
      total Cd, P, U and NaHCO3-extractable U concentrations, and 234/238U activity
      ratios (AR). The U concentrations and AR values of the drinking water samples
      were also measured. A theoretical assessment showed that fertilizer-derived U may
      cause high U concentrations in leaching waters (up to approx. 25 MUg L-1), but
      normally contributes only a small amount (approx. 0-3 MUg L-1). The arable soils
      investigated showed no significant U accumulation compared to the forest sites.
      The close positive correlation of AR with NaHCO3-extractable U (R = 0.7, p <
      0.001) indicates that application of fertilizer can increase the extractable U
      pool. The lack of depth gradients in the soil U concentrations (1.5-2.7 mg kg-1)
      and AR (0.90-1.06) ratios are inconsistent with the accumulation of U in the
      surface soil, and might indicate some leaching of fertilizer-derived U. The AR
      values in the water samples were close to 1, possibly suggesting an influence of
      fertilizer-derived U. However, based on findings from the literature and
      considering the heterogeneity of the catchment area, the agricultural practices,
      and the comparatively long distance to the groundwater, we conclude that
      fertilizer-derived U makes only a minor contribution to the elevated U
      concentrations in the water samples.

PMID- 29029837
TI  - A review of current evidence regarding the ICD-11 proposals for diagnosing PTSD
      and complex PTSD.
AB  - The World Health Organization's proposals for posttraumatic stress disorder
      (PTSD) in the 11th edition of the International Classification of Diseases,
      scheduled for release in 2018, involve a very brief set of symptoms and a
      distinction between two sibling disorders, PTSD and Complex PTSD. This review of
      studies conducted to test the validity and implications of the diagnostic
      proposals generally supports the proposed 3-factor structure of PTSD symptoms,
      the 6-factor structure of Complex PTSD symptoms, and the distinction between PTSD
      and Complex PTSD. Estimates derived from DSM-based items suggest the likely
      prevalence of ICD-11 PTSD in adults is lower than ICD-10 PTSD and lower than DSM
      IV or DSM-5 PTSD, but this may change with the development of items that directly
      measure the ICD-11 re-experiencing requirement. Preliminary evidence suggests the
      prevalence of ICD-11 PTSD in community samples of children and adolescents is
      similar to DSM-IV and DSM-5. ICD-11 PTSD detects some individuals with
      significant impairment who would not receive a diagnosis under DSM-IV or DSM-5.
      ICD-11 CPTSD identifies a distinct group who have more often experienced multiple
      and sustained traumas and have greater functional impairment than those with
      PTSD.

PMID- 29029838
TI  - Global analysis of neurological disease: burden and benefit.

PMID- 29029840
TI  - Pathology and hippocampal atrophy in Alzheimer's disease.

PMID- 29029839
TI  - Restless legs syndrome: is it all in the genes?

PMID- 29029841
TI  - Challenges and unfulfilled promises in Parkinson's disease.

PMID- 29029842
TI  - Palliative care in neurology.

PMID- 29029843
TI  - Palliative care in neurology.

PMID- 29029844
TI  - Trying to change the stroke landscape in Nigeria.

PMID- 29029845
TI  - Andrew Maas (and the bird on his shoulder).

PMID- 29029847
TI  - The diagnostic challenge of small fibre neuropathy: clinical presentations,
      evaluations, and causes.
AB  - Small fibre neuropathies are a heterogeneous group of disorders affecting thinly
      myelinated Adelta-fibres and unmyelinated C-fibres. Although multiple causes of
      small nerve fibre degeneration have been reported, including via genetic
      mutations, the cause of small fibre neuropathy remains unknown in up to 50% of
      cases. The typical clinical presentation of small fibre neuropathy is that of a
      symmetrical, length-dependent polyneuropathy associated with sensory or autonomic
      symptoms. More rarely, the clinical presentation is characterised by non-length
      dependent, focal, or multifocal symptoms. The diagnostic tests to identify small
      fibre neuropathy include skin biopsy, quantitative sensory, and autonomic
      testing. Additional tests, such as those measuring small fibre-related evoked
      potentials and corneal confocal microscopy, might contribute to a better
      understanding of these neuropathies. Biochemical markers can also help in
      screening patients for the presence of small fibre neuropathy and to assess
      disease progression.

PMID- 29029848
TI  - Fluoride containing bioactive glass composite for orthodontic adhesives - ion
      release properties.
AB  - OBJECTIVE: Dental materials that release calcium, phosphate and fluoride ions
      could prevent demineralisation and/or enhance remineralisation of enamel. The
      objective was to develop a novel bioactive glass (BAG) resin and investigate pH
      changes and ion release in 3 immersion media. METHODS: Quench melt derived BAG
      (35.25% SiO2, 6% Na2O, 43% CaO, 5.75% P2O5, and 10% CaF2) was incorporated into a
      resin (42.25% BisEMA, 55% TEGDMA, 0.25% DMAEM, 0.5% camphorquinone and 2% 4
      Meta), with a filler load of 80% by weight. Ninety composite disks for each BAG
      loading of 80%, 60%, 50%, 40%, 20%, and 0% were made and each disk was immersed
      in 10ml of either tris buffer (TB), or artificial saliva at pH=7 (AS7) or pH=4
      (AS4), n=30 for each solution. Three disks of each loading were taken from each
      of the solutions, at ten time points (6h-6months), for measurement of pH,
      fluoride, calcium and phosphate. RESULTS: The BAG adhesive raised the pH in all
      the solutions, release Ca, PO4 and F ions especially in AS4. The rise in pH and
      the release of Ca and F are directly related to the BAG loading and the time of
      immersion. The pH and the ion releases were maintained and continued over
      6months. SIGNIFICANCE: Unlike glass ionomer resins, favourable ions F, Ca and PO4
      releases were maintained over a long time period especially in acidic condition
      for this novel BAG-resin composite. This indicates the resin has the potential to
      prevent formation and progression of early caries lesions.

PMID- 29029849
TI  - Impact of the heating/quenching process on the mechanical, optical and
      thermodynamic properties of polyetheretherketone (PEEK) films.
AB  - OBJECTIVE: The aim of this study was to investigate the impact of a
      heating/quenching process on the optical, mechanical and thermodynamic properties
      of filled (20%_4000) and unfilled PEEK films (0%_2000 and 0%_4000).
      Heating/quenching was performed to simulate thermoforming as possible method to
      process thermoplastic polymers for dental application. METHODS: For the
      investigation, films of different PEEK qualities (0%_2000, 0%_4000, 20%_4000)
      were produced using isostatic pressing (n=10/quality). From each PEEK film, round
      specimens (n=20/PEEK film) with a diameter of 34mm were cut and following
      parameters were determined: translucency (T%), Martens-Hardness (HM), indentation
      modulus (EIT), glass transition temperature (TG), melting temperature (TM) and
      enthalpy of fusion (DeltaHf). Same specimens were exposed to heating/quenching
      using defined parameters. Afterwards, T%, HM, EIT, TG, TM and DeltaHf were
      determined again. Data were analysed using Kolmogorov-Smirnov test, univariate
      ANOVA followed by post-hoc Scheffe test with partial eta squared (etap2), Kruskal
      Wallis and Mann Whitney U test. Level of significance was defined to 95%.
      RESULTS: Materials showed significant differences for all investigated parameters
      in the initial state, except of TG (p=0.249). The heating/quenching process
      showed a significant increase on T% for the unfilled materials 0%_2000 and
      0%_4000. HM and EIT decreased significantly through heating/quenching for all
      materials. Moreover, heating/quenching showed a reduction of TG for 0%_2000 and
      20%_4000, while TM decreased for 0%_2000 and 0%_4000. DeltaHf confirms different
      crystallinities of tested materials. SIGNIFICANCE: The heating/quenching process
      showed a significant impact on all investigated parameters. The highest impact
      was found for mechanical properties resulting in decreased values of HM and EIT.

PMID- 29029850
TI  - Surface characteristics of dental implants: A review.
AB  - OBJECTIVES: During the last decades, several changes of paradigm have modified
      our view on how biomaterials' surface characteristics influence the bioresponse.
      After becoming aware of the role of a certain microroughness for improved
      cellular contact and osseointegration of dental titanium implants, the likewise
      important role of surface energy and wettability was increasingly strengthened.
      Very recently, synergistic effects of nanoscaled topographical features and
      hydrophilicity at the implant/bone interface have been reported. METHODS:
      Questions arise about which surface roughness and wetting data are capable to
      predict the bioresponse and, ultimately, the clinical performance. Current
      methods and approaches applied for topographical, wetting and surface energetic
      analyses are highlighted. Current knowledge of possible mechanisms explaining the
      influence of roughness and hydrophilicity at the biological interface is
      presented. RESULTS: Most marketed and experimental surfaces are based on commonly
      available additive or subtractive surface modifying methods such as blasting,
      etching or anodizing. Different height, spatial, hybrid and functional roughness
      parameters have been identified as possible candidates able to predict the
      outcome at hard and soft tissue interfaces. Likewise, hydrophilic implants have
      been proven to improve the initial blood contact, to support the wound healing
      and thereby accelerating the osseointegration. SIGNIFICANCE: There is clear
      relevance for the influence of topographical and wetting characteristics on a
      macromolecular and cellular level at endosseous implant/biosystem interfaces.
      However, we are still far away from designing sophisticated implant surfaces with
      the best possible, selective functionality for each specific tissue or cavity
      interface. Firstly, because our knowledge of the respective surface related
      reactions is at best fragmentary. Secondly, because manufacturing of multi-scaled
      complex surfaces including distinct nanotopographies, wetting properties, and
      stable cleanliness is still a technical challenge and far away from being
      reproducibly transferred to implant surfaces.

PMID- 29029852
TI  - Human adipose tissue-derived stem cells inhibit the activity of keloid
      fibroblasts and fibrosis in a keloid model by paracrine signaling.
AB  - BACKGROUND: Human adipose tissue-derived mesenchymal stem cells (ASCs) have
      potential utility as modulators of the regeneration of tissue that is inflamed or
      scarred secondary to injuries such as burns or trauma. However, the effect of
      ASCs on one particular type of scarring, keloidal disease, remains unknown. The
      absence of an optimal model for investigation has hindered the development of an
      effective therapy using ASCs for keloids. OBJECTIVE: To investigate the influence
      of ASCs on angiogenesis, extracellular matrix deposition, and inflammatory cell
      influx in keloids. METHODS: We analyzed the proliferation, migration, and
      apoptosis of human keloid-derived fibroblasts treated with a starvation-induced,
      conditioned medium from ASCs (ASCs-CM). This was achieved by Brdu proliferation
      assay, a validated co-culture migration assay, and flow cytometry, respectively.
      To assess the change in phenotype to a pro-fibrotic state, fibroblasts were
      analyzed by real-time PCR and contraction assay. A keloid implantation animal
      model was used to assess the paracrine effect of ASCs histochemically and
      immunohistochemically on scar morphology, collagen deposition, inflammatory cell
      composition, and blood vessel density. In tandem, an antibody-based array was
      used to identify protein concentration in the presence of ASCs-CM at time point
      0, 24, and 48h. RESULTS: ASCs-CM inhibited the proliferation and collagen
      synthesis of human keloid-derived fibroblasts. ASCs-CM was associated with
      reduced inflammation and fibrosis in the keloid implantation model. Thirty-four
      cytokines were differentially regulated by ASCs-CM at 24h. These included
      molecules associated with apoptosis, matrix metalloproteases, and their
      inhibitors. The same molecules were present at relatively higher concentrations
      at the 48h timepoint. CONCLUSION: These results suggest that ASCs are associated
      with the inhibition of fibrosis in keloids by a paracrine effect. This phenomenon
      may have utility as a therapeutic approach in the clinical environment.

PMID- 29029853
TI  - Response to Letter to the Editor 'Long term mortality in critically ill burn
      survivors: Methodological issues'.

PMID- 29029846
TI  - Identification of novel risk loci for restless legs syndrome in genome-wide
      association studies in individuals of European ancestry: a meta-analysis.
AB  - BACKGROUND: Restless legs syndrome is a prevalent chronic neurological disorder
      with potentially severe mental and physical health consequences. Clearer
      understanding of the underlying pathophysiology is needed to improve treatment
      options. We did a meta-analysis of genome-wide association studies (GWASs) to
      identify potential molecular targets. METHODS: In the discovery stage, we
      combined three GWAS datasets (EU-RLS GENE, INTERVAL, and 23andMe) with diagnosis
      data collected from 2003 to 2017, in face-to-face interviews or via
      questionnaires, and involving 15 126 cases and 95 725 controls of European
      ancestry. We identified common variants by fixed-effect inverse-variance meta
      analysis. Significant genome-wide signals (p<=5 * 10-8) were tested for
      replication in an independent GWAS of 30 770 cases and 286 913 controls, followed
      by a joint analysis of the discovery and replication stages. We did gene
      annotation, pathway, and gene-set-enrichment analyses and studied the genetic
      correlations between restless legs syndrome and traits of interest. FINDINGS: We
      identified and replicated 13 new risk loci for restless legs syndrome and
      confirmed the previously identified six risk loci. MEIS1 was confirmed as the
      strongest genetic risk factor for restless legs syndrome (odds ratio 1.92, 95% CI
      1.85-1.99). Gene prioritisation, enrichment, and genetic correlation analyses
      showed that identified pathways were related to neurodevelopment and highlighted
      genes linked to axon guidance (associated with SEMA6D), synapse formation
      (NTNG1), and neuronal specification (HOXB cluster family and MYT1).
      INTERPRETATION: Identification of new candidate genes and associated pathways
      will inform future functional research. Advances in understanding of the
      molecular mechanisms that underlie restless legs syndrome could lead to new
      treatment options. We focused on common variants; thus, additional studies are
      needed to dissect the roles of rare and structural variations. FUNDING: Deutsche
      Forschungsgemeinschaft, Helmholtz Zentrum Munchen-Deutsches Forschungszentrum fur
      Gesundheit und Umwelt, National Research Institutions, NHS Blood and Transplant,
      National Institute for Health Research, British Heart Foundation, European
      Commission, European Research Council, National Institutes of Health, National
      Institute of Neurological Disorders and Stroke, NIH Research Cambridge Biomedical
      Research Centre, and UK Medical Research Council.

PMID- 29029851
TI  - Arresting Evolution.
AB  - Evolution in the form of selective breeding has long been harnessed as a useful
      tool by humans. However, rapid evolution can also be a danger to our health and a
      stumbling block for biotechnology. Unwanted evolution can underlie the emergence
      of drug and pesticide resistance, cancer, and weeds. It makes live vaccines and
      engineered cells inherently unreliable and unpredictable, and therefore
      potentially unsafe. Yet, there are strategies that have been and can possibly be
      used to stop or slow many types of evolution. We review and classify existing
      population genetics-inspired methods for arresting evolution. Then, we discuss
      how genome editing techniques enable a radically new set of approaches to limit
      evolution.

PMID- 29029854
TI  - Hospitalized burns in Finland: 36305 cases from 1980-2010.
AB  - To analyse the epidemiology of burns in Finland, a comprehensive study was
      conducted among all hospitalized burn patients between 1980 and 2010. All
      patients with burn injury as the main diagnosis, 36305 cases in total, treated in
      the public and private sectors, were included. Patient data were obtained from
      the Finnish Hospital Discharge Register (FHDR). The incidence of hospitalized
      injuries declined from over 30 to 17 per 100000 persons. Men were at higher risk
      than women in all age groups. Children aged under ten years were overrepresented
      throughout the period and the highest incidence was found among one year old
      boys. The median total length of stay shortened from seven days in 1980-1995 to
      five days in 1996-2010. The annual number of hospitalized patients is recently
      under 1000 cases (17/100000). The male predominance (70%) did not change but the
      age group with the most injuries shifted from 20-39 years to 40-59 years.
      Injuries were most common during the summer months. This study of all
      hospitalized burn injuries of one entire country shows similar tendency of
      diminishing numbers and rising age of burn victims as in other western countries.
      The FHDR is a reliable source of data in epidemiological studies but precise
      recording of E- and N-codes in the registry would enable the accurate analysis of
      types and extent of injury.

PMID- 29029855
TI  - Improving mortality outcomes of Stevens Johnson syndrome/toxic epidermal
      necrolysis: A regional burns centre experience.
AB  - INTRODUCTION: Stevens Johnson Syndrome/toxic epidermal necrolysis (SJS/TEN) are
      rare, potentially fatal desquamative disorders characterised by large areas of
      partial thickness skin and mucosal loss. The degree of epidermal detachment that
      occurs has led to SJS/TEN being described as a burn-like condition. These
      patients benefit from judicious critical care, early debridement and meticulous
      wound care. This is best undertaken within a multidisciplinary setting led by
      clinicians experienced in the management of massive skin loss and its sequelae.
      In this study, we examined the clinical outcomes of SJS/TEN overlap & TEN
      patients managed by our regional burns service over a 12-year period. We present
      our treatment model for other burn centres treating SJS/TEN patients. METHODS: A
      retrospective case review was performed for all patients with a clinical
      diagnosis of TEN or SJS/TEN overlap admitted to our paediatric and adult burns
      centre between June 2004 and December 2016. Patient demographics, percentage
      total body surface area (%TBSA), mucosal involvement, causation, severity of
      illness score (SCORTEN), length of stay and survival were appraised with
      appropriate statistical analysis performed using Graph Pad Prism 7.02 Software.
      RESULTS: During the study period, 42 patients (M26; F: 16) with TEN (n=32) and
      SJS/TEN overlap (n=10) were managed within our burns service. Mean %TBSA of
      cutaneous involvement was 57% (range 10-100%) and mean length of stay (LOS) was
      27 days (range 1-144 days). We observed 4 deaths in our series compared to 16
      predicted by SCORTEN giving a standardised mortality ratio (SMR) of 24%.
      CONCLUSION: Management in our burns service with an aggressive wound care
      protocol involving debridement of blistered epidermis and wound closure with
      synthetic and biological dressings seems to have produced benefits in mortality
      when compared to predicted outcomes.

PMID- 29029856
TI  - What about HES in burn patients?: Evaluation of the actual evidence.

PMID- 29029857
TI  - The clinical utility of extracorporeal shock wave therapy for burn pruritus: A
      prospective, randomized, single-blind study.
AB  - PURPOSES: To investigate the effect and mechanisms of extracorporeal shock wave
      therapy (ESWT) on burn scar pruritus. METHODS: Forty-six patients participated
      (experimental group, n=23; sham stimulation group, n=23). Patients had complaints
      of severe pruritus ranging from 5 to 10 on the visual analog scale. The
      experimental group received 1000-2000 shock waves for each treatment with 100
      impulses/cm2, each with low-energy flux density (0.05-0.20mJ/mm2) and a 1-week
      interval between treatments for 3 weeks. The numerical rating scale (NRS), 5D
      Itch Scale, and Leuven Itch Scale were evaluated immediately before ESWT and
      after the third session. Laser Doppler blood perfusion imaging (LDI) was
      performed immediately before ESWT and after the first and third sessions.
      RESULTS: In the experimental group, mean NRS scores were 6.30+/-1.29 before
      therapy and 3.57+/-2.09 after the third session, and the difference was
      significant (p<0.001). NRS scores in the experimental group after the third ESWT
      were significantly decreased compared to those of the sham stimulation group
      (p=0.009). The duration, severity, and consequences scores of pruritus on the
      Leuven Itch Scale after the third ESWT were significantly decreased in the
      experimental group compared with the sham stimulation group (p=0.033, p=0.007,
      and p=0.009, respectively). The direction score on the 5-D Itch Scale after the
      third ESWT was significantly decreased in the experimental group compared to the
      sham stimulation group (p=0.033). After the first ESWT session and after 3
      sessions, the burn area had a significant increase in perfusion according to LDI,
      compared with the scores before treatment in the experimental group (p=0.023 and
      p=0.013, respectively). CONCLUSION: ESWT is a non-invasive modality that
      significantly reduced burn-associated pruritus.

PMID- 29029858
TI  - The WHO well known report on preventing suicide has neglected self-immolation.

PMID- 29029859
TI  - Intensive insulin therapy, insulin sensitisers and insulin secretagogues for
      burns: A systematic review of effectiveness and safety.
AB  - This systematic review investigated the effectiveness and safety of intensive
      insulin therapy (IIT), insulin secretagogues and sensitisers in burn patients.
      PubMed, Embase, clinicaltrials.gov and Cochrane central were searched from 1990
      to 2016. Title/abstract screening, full-text review, critical appraisal and data
      extraction were carried out by two independent reviewers. Inclusion criteria were
      hospitalised burn patients, IIT, insulin sensitisers or secretagogues and the
      outcomes mortality, length of stay, resting energy expenditure, blood glucose,
      catabolism, or complications. We identified 594 potential studies of which 13
      were included. Five studies investigated IIT in paediatric patients, 3
      investigated IIT in adults and 5 investigated sensitisers or secretagogues.
      Glycaemic targets differed with age group - paediatric studies compared IIT to
      loose glycaemic control while adult studies compared IIT to more moderate
      control. Meta-analyses were limited by differences in outcome reporting, however
      mortality was increased in children by loose glycaemic control (OR=3.78, 95%CI
      1.19-12.02) but not significantly affected in adults by moderate compared to
      tight control. Meta-analyses could not be performed for sensitisers or
      secretagogues. These findings support recommendations that moderate insulin
      administration (130-150mg/dL) is the prudent approach in burn patients. The
      evidence is relatively sparse and further research is warranted.

PMID- 29029860
TI  - Chemical burns: Diphoterine untangled.
AB  - OBJECTIVE: Diphoterine is a hypertonic, amphoteric, polyvalent and chelating
      decontamination solution used in the treatment of cutaneous and ocular chemical
      burns. Due to infrequent use by emergency physicians along with the small number
      of available studies, its debate in the literature as to its efficacy and safety
      remains inconclusive. METHODS: A structured literature search was performed in
      MEDLINE, EMBASE BIOLOGICAL ABSTRACTS and TOXNET to June 2016 for original English
      language studies reporting on the safety and effectiveness of Diphoterine.
      Methodological and reporting quality of pre-clinical animal studies was assessed
      using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE)
      risk of bias tool and Animal Research: Reporting of In Vivo Experiments (ARRIVE)
      guidelines. Clinical studies were assessed using Chambers' criteria. RESULTS: 13
      studies (seven in the pre-clinical, five in the clinical setting and one mixed)
      met the study inclusion criteria. Pre-clinical studies showed a faster resolution
      of pH and reduced tissue necrosis with Diphoterine. Clinical studies showed
      reduced tissue necrosis/severity of symptoms, faster pH resolution and a
      reduction in pain when using Diphoterine. No adverse events were attributable to
      Diphoterine. Reporting and methodology of the studies was poor or showed a high
      risk of bias. CONCLUSIONS: Diphoterine appears to be safe to use and is probably
      superior to other rinsing solutions. However, immediate decontamination is
      imperative and if Diphoterine is not available a different rinsing solution
      should be used. The methodology of the published literature for Diphoterine is
      generally poor and future publications should use the frameworks given as
      templates.

PMID- 29029861
TI  - Burn injury outcomes in patients with pre-existing diabetic mellitus: Risk of
      hospital-acquired infections and inpatient mortality.
AB  - BACKGROUND: Diabetes mellitus (DM) is a major cause of illness and death in the
      United States, and diabetic patients are at increased risk for burn injury. We
      therefore sought to examine the impact of pre-existing DM on the risk of
      inpatient mortality and hospital acquired infections (HAI) among burn patients.
      METHODS: Adult patients (>=18 years old) admitted from 2004 to 2013 were
      analyzed. Weighted Kaplan-Meier survival curves - adjusting for patient
      demographics, burn mechanism, presence of inhalation injury, total body surface
      area, additional comorbidities, and differential lengths of stay - were used to
      estimate the 30-day and 60-day risk of mortality and HAIs. RESULTS: A total of
      5539 adult patients were admitted and included in this study during the study
      period. 655 (11.8%) had a pre-existing DM. The crude incidence of HAIs and in
      hospital mortality for the whole burn cohort was 8.5% (n=378) and 4.4% (n=243),
      respectively. Diabetic patients were more likely to be older, female, have
      additional comorbidities, inhalational injury, and contact burns. After adjusting
      for patient and burn characteristics, the 60-day risk of HAI among patients with
      DM was significantly higher, compared to non-diabetic patients (RR 2.07, 95% CI
      1.28, 6.79). However, no significant difference was seen in the 60-day risk of
      mortality (RR 1.34, 95% CI 0.44, 3.10). CONCLUSIONS: Pre-existing DM
      significantly increases the risk of developing an HAI in patients following burn
      injury, but does not significantly impact the risk of inpatient mortality.
      Further understanding of the immune modulatory mechanism of burn injury and DM is
      imperative to better attenuate the acquisition of HAIs.

PMID- 29029862
TI  - Hidden dangers revealed by misdiagnosed diabetic neuropathy: A comparison of
      simple clinical tests for the screening of vibration perception threshold at
      primary care level.
AB  - AIM: Diabetic peripheral neuropathy is an important complication and contributes
      to the morbidity of diabetes mellitus. Evidence indicates early detection of
      diabetic peripheral neuropathy results in fewer foot ulcers and amputations. The
      aim of this study was to compare different screening modalities in the detection
      of diabetic peripheral neuropathy in a primary care setting. METHOD: A
      prospective non-experimental comparative multi-centre cross sectional study was
      conducted in various Primary Health Centres. One hundred participants living with
      Type 2 diabetes for at least 10 years were recruited using a convenience sampling
      method. The Vibratip, 128Hz tuning fork and neurothesiometer were compared in the
      detection of vibration perception. RESULTS: This study showed different results
      of diabetic peripheral neuropathy screening tests, even in the same group of
      participants. This study has shown that the percentage of participants who did
      not perceive vibrations was highest when using the VibraTip (28.5%). This was
      followed by the neurothesiometer (21%) and the 128Hz tuning fork (12%) (p<0.001).
      CONCLUSION: Correct diagnosis and treatment of neuropathy in patients with
      diabetes is crucial. This study demonstrates that some instruments are more
      sensitive to vibration perception than others. We recommend that different
      modalities should be used in patients with diabetes and when results do not
      concur, further neurological evaluation should be performed. This would
      significantly reduce the proportion of patients with diabetes who would be
      falsely identified as having no peripheral neuropathy and subsequently denied the
      benefit of beneficial and effective secondary risk factor control.

PMID- 29029864
TI  - Elective repeat caesarean delivery may affect bone mineral density compared with
      normal vaginal delivery.

PMID- 29029863
TI  - Changes in Local Bone Density in Early Thumb Carpometacarpal Joint
      Osteoarthritis.
AB  - PURPOSE: Thumb carpometacarpal (CMC) osteoarthritis (OA) represents a major
      source of functional morbidity. The effects of early CMC OA on loading and use
      patterns potentially lead to changes in local bone density and microarchitecture.
      Hounsfield units (HU), a quantitative attenuation coefficient obtained from
      computed tomography (CT) scans, have been shown to be a reliable marker of bone
      density. We hypothesized that early CMC OA is associated with lower local bone
      density about the CMC joint as assessed by HU. METHODS: We examined HU units from
      CT scans in 23 asymptomatic subjects and 91 patients with early CMC OA. The HU
      measurements were obtained within cancellous portions of the trapezium, capitate,
      first and third metacarpal bases, and distal radius. Linear regression models,
      with age and sex included as covariates, were used to assess the relationship
      between CMC OA and HU values at each anatomical site. RESULTS: Early OA patients
      had significantly lower HU than asymptomatic subjects within the trapezium (mean,
      377 HU vs 436 HU) and first metacarpal bases (265 HU vs 324 HU). No significant
      group differences were noted at the capitate, third metacarpal, or distal radius.
      Male sex and younger age were associated with significantly higher HU at all the
      anatomical sites, except the first metacarpal base, where age had no significant
      effect. CONCLUSIONS: Subjects presenting with early CMC OA had significantly
      lower bone density as assessed with HU at the thumb CMC joint (trapezium and
      first metacarpal base). Early thumb CMC OA and discomfort may lead to diminished
      loading across the basal joint, producing focal disuse osteopenia. These findings
      in symptomatic early arthritis suggest a relationship between symptoms,
      functional use of the CMC joint, and local bone density. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Diagnostic II.

PMID- 29029865
TI  - Total proteolytic activity and concentration of alpha-1 antitrypsin in meconium
      for assessment of the protease/antiprotease balance.
AB  - BACKGROUND: During intrauterine life, various proteolytic enzymes and their main
      inhibitor, alpha-1 antitrypsin, accumulate naturally in meconium. A
      protease/antiprotease balance is required to maintain the biological stability of
      the environment in which the fetus develops. METHODS: The pool of active
      proteases was determined using the EnzChek Protease Assay Kit. The concentration
      of alpha-1 antitrypsin in meconium was measured by enzyme-linked immunosorbent
      assay. Serial portions of meconium (n=80) were collected from healthy full-term
      neonates (n=19). RESULTS: Mean concentrations of active proteases and alpha-1
      antitrypsin were 1.55 [standard deviation (SD) 1.3]mgg-1 (range 0.15-6.17) and
      3.72 (SD 1.78)mgg-1 (range 0.76-8.55), respectively, with significant correlation
      (Rs=0.32, p=0.004). A significant increase in the concentration of active
      proteases was found between the first and last meconium portions (p<0.05). The
      proteases in the last meconium portions had a higher reaction velocity and
      affinity for the substrate than the proteases in the first meconium portions. The
      active protease:alpha-1 antitrypsin ratio was <0.5 in all first meconium
      portions, but was higher in the last meconium portions. CONCLUSIONS: Strong
      correlation between the concentrations of active proteases and alpha-1
      antitrypsin in meconium may indicate their mutual interaction in the intrauterine
      environment. Alpha-1 antitrypsin maintains the protease/antiprotease balance
      during fetal development.

PMID- 29029866
TI  - Optic Chiasm Involvement With Concurrent Typical Wernicke Encephalopathy Magnetic
      Resonance Findings: A Case Report.
AB  - The variable clinical presentation of Wernicke encephalopathy often complicates
      interpretation. Prompt and accurate diagnosis relies on a constellation of
      typical and atypical magnetic resonance imaging (MRI) findings, which are not
      always simultaneously present. Our case demonstrates concurrent presentation of
      all typical Wernicke encephalopathy MRI findings with additional signal
      abnormalities involving the optic chiasm and optic tract. We suggest that optic
      pathway involvement may be considered among several atypical MRI manifestations,
      reinforcing the prompt diagnosis of the potentially life-threatening
      encephalopathy.

PMID- 29029867
TI  - A Text Messaging Intervention to Support Option B+ in Kenya: A Qualitative Study.
AB  - Key challenges in providing lifelong antiretroviral therapy (ART) to pregnant and
      breastfeeding women (Option B+) in sub-Saharan Africa include achieving long-term
      adherence and retention in care. One intervention that may help address these
      challenges is mobile text messaging. We evaluated the acceptability of a text
      messaging intervention to support women's ART adherence and retention in care in
      rural western Kenya. Forty in-depth interviews with 20 pregnant/postpartum women
      infected with HIV, their male partners, and four focus groups with 30 health care
      providers were conducted during September-November 2014. Data were coded and
      analyzed using thematic analysis. Findings revealed the following themes: (a)
      overall acceptability of the text messaging intervention; (b) proposed content of
      text messages; (c) format, timing, and language of text messages; and (d)
      potential challenges of the text messaging intervention. Findings were used to
      refine a text messaging intervention being evaluated at Kenyan study sites
      rolling out Option B+.

PMID- 29029868
TI  - Does severe osteoarthritis in knees with varus deformity alter the adductor
      ratio?
AB  - OBJECTIVE: In our retrospective study, we aimed to investigate the differences
      between the adductor ratio (AR) in knees with and without osteoarthritis, and its
      validity in determining the articular level. METHODS: Data from 80 knees of 80
      patients were retrospectively evaluated. Anteroposterior weight-bearing knee
      radiographs of the patients with and without osteoarthritis (40 knees in each
      group) were obtained. The adductor ratio was determined using the following
      formula: ATJL/FW (adductor tubercle-joint line distance/femoral width). All
      radiographs were evaluated at the baseline and at one-month intervals afterwards.
      Intraobserver reliability of the two measurements was assessed using interclass
      correlations (ICC). Pearson's correlation test was used to evaluate the
      correlation between the ATJL and the FW. The differences between the adductor
      ratios of the two groups were evaluated by the independent samples two-tailed t
      test. RESULTS: Most of the ICC values were well above 0.95, indicating a very
      high intraobserver reliability. The adductor ratio was significantly greater in
      Group 2 in comparison to Group 1 (Mean AR in Group 2: 0.522 +/- 0.031 and Mean AR
      in Group 1: 0.502 +/- 0.032; p = 0.005). There was a significant correlation
      between the ATJL and FW in the groups when assessed both separately and combined.
      CONCLUSION: In conclusion, we can assert that if the AR is used to determine the
      articular level in revision arthroplasty cases, it may be sensible to measure the
      FW intraoperatively rather than measuring it on primary or contralateral
      radiographs of arthritic patients. LEVEL OF EVIDENCE: Level III, Diagnostic
      study.

PMID- 29029870
TI  - An obesity paradox with myocardial infarction in the elderly.

PMID- 29029869
TI  - Determination of the hip rotation centre from landmarks in pelvic radiograph.
AB  - OBJECTIVE: The hip rotation centre (HRC) is an important reference point in cases
      of total hip arthroplasty (THA). The aim of this study is to investigate the
      reference points in the Turkish population that enable the identification of the
      HRC in standard pelvic radiographs. METHODS: The pelvic radiographs of 50 women
      and 50 men were examined. The mean age was 46.2 (range; 18-91). Patients with
      deformity of the hip joint and non-standard pelvic radiograph due to hip flexion
      contracture were excluded from the study. The pelvic height (PH), the distance
      between the HRC and teardrop (HRC-Td), and the HRC and the line tangent tuber
      ischiadicums (HRC-TI) were measured. The ratio of HRC-Td and HRC-TI to PH were
      calculated. The first is called "the horizontal-HRC ratio" and the second, "the
      vertical-HRC ratio". RESULTS: Mean PH was 239 (+/-13.58) mm in males and 225 (+/
      12.52) in females (p < 0.0001). The distances of HRC-TI were 71 (+/-6.35) and 65
      (+/-6.72) mm (p < 0.0001) and the distance of HRC-Td were 34 (+/-3.73) and 30 (+/
      4.05) mm (p = 0.0007), respectively. The vertical-HRC ratios were 30.01% (+/
      2.05) for males, 29.10% (+/-2.35) for females, the horizontal-HRC ratio, 14.25%
      (+/-1.42) and 13.69% (+/-1.38), respectively (p > 0.05). CONCLUSION: Although the
      quantitative values obtained in the present study differ between the genders, the
      ratios ("vertical-HRC" and "horizontal-HRC") are comparable in both sexes. The
      results show that these proposed ratios can be used in THA planning, regardless
      of gender in the Turkish population LEVEL OF EVIDENCE: Level IV, diagnostic
      study.

PMID- 29029871
TI  - Nanocasting synthesis of chromium doped mesoporous CeO2 with enhanced visible
      light photocatalytic CO2 reduction performance.
AB  - Chromium doped mesoporous CeO2 catalysts were synthesized via a simple
      nanocasting route by using silica SBA-15 as the template and metal nitrates as
      precursors. The effect of Cr doping concentration (5%, 10%, 15% and 20% of the
      initial Cr/(Cr+Ce) molar percentage) on the structures of these catalysts and
      their photocatalytic performances in reduction of CO2 with H2O were investigated.
      The results indicated that the introduction of Cr species could effectively
      extend the spectral response range from UV to visible light region (400-700nm)
      and improve the electronic conductivity for the mesoporous CeO2 catalysts which
      exhibited an enhanced photocatalytic activity in the reduction of CO2 with H2O
      when compared with the non-doped counterpart. The highest CO and CH4 yield of
      16.2MUmol/g-cat. and 10.1MUmol/g-cat., respectively, were acquired on the optimal
      chromium doped CeO2 catalyst with the initial Cr(Cr+Ce) molar percentage of 15%
      under 8h visible-light irradiation, which were more than twice as high as that of
      bare CeO2. The remarkably increased photocatalytic performance should be
      attributed to the advantageous structural and compositional features of the
      chromium doped mesoporous CeO2.

PMID- 29029872
TI  - Inhibition of deubiquitinases alters gamete ubiquitination states and sperm
      oocyte binding ability in pigs.
AB  - This study was undertaken to investigate the dynamics of protein ubiquitination
      in pig gametes and their micro-environments, as well as to explore the action of
      deubiquitinases (DUBs) in sperm-oocyte binding. Protein ubiquitination states
      were evaluated by in the ejaculated sperm, seminal plasma, epididymal sperm,
      oocytes, zona pellucida (ZP) and follicular fluid (FF) by western blotting.
      Different concentrations of PR-619, a non-selective inhibitor of DUBs, were used
      to treat oocytes during in vitro maturation (IVM), the maturation rate, amount of
      ubiquitinated ZP proteins, and ZP solubility were assessed. The PR-619 was also
      used to treat sperms during capacitation, then the ubiquitinated amounts of
      acrosin inhibitor (AI) proteins were evaluated. The number of sperm attached to
      the ZP of each oocyte was subsequently determined after gamete co-incubation. The
      study indicates the existence of ubiquitinated proteins (76kDa) in sperm, seminal
      plasma, oocytes, and follicular fluid (FF). The amount of ubiquitinated ZP
      proteins changed as growth of follicles progressed. Treatment with PR-619 at 10
      and 15MUM concentrations during IVM reduced the maturation rate of pig oocytes
      (P<0.05), while treatments with 10MUM of PR-619 extended the ZP dissolution time
      (P<0.05). Treatment with PR-619 enhanced AI ubiquitination and improved amounts
      of 30-kDa ubiquitinated proteins (P<0.05). Treatment with PR-619 at the 10MUM
      dose effectively reduced the number of sperm attached to per oocyte (P<0.05).
      Ubiquitinated proteins were present in gametes and their micro-environments. The
      DUBs were important in regulating pig gamete ubiquitination and sperm-oocyte
      binding.

PMID- 29029873
TI  - Prediction of calving time in dairy cattle.
AB  - This prospective study was carried out to predict the calving time in primiparous
      (n=11) and multiparous (n=22) Holstein-Friesian cows using the combination of
      data obtained from the RumiWatch noseband-sensor and 3D-accelerometer. The
      animals included in the study were fitted with the RumiWatch noseband-sensor and
      3D-accelerometer at least 10days before the expected calving day. The calving
      event was defined as the time of the first appearance of the calves' feet outside
      the vulva, and this moment was determined by farm staff and/or confirmed by video
      monitor. As primiparous and multiparous cows behaved differently, two models
      including data of noseband-sensors and 3D-accelerometers were used to predict the
      calving time in each group. Lying bouts (LB) increased and rumination chews (RC)
      decreased similarly in both groups; besides that, boluses (B) decreased and other
      activities (OA) increased significantly in multiparous and primiparous cows,
      respectively. The sensitivity (Se) and specificity (Sp) for prediction of the
      onset of calving within the next 3h were determined with the logistic regression
      and ROC analysis (Se=88.9%, 85% and Sp=93.3%, 74% for multiparous and primiparous
      cows, respectively). This pilot study revealed that the RumiWatch system is a
      useful tool to predict calving time under farm conditions.

PMID- 29029874
TI  - Sperm subpopulations in ejaculated sperm and spermatozoa recovered from ovine
      epididymides up to 48h after death.
AB  - The objectives of this study were threefold: to identify subpopulations of sperm
      based on the kinetics of frozen/thawed sheep epididymal spermatozoa or semen
      collected with an artificial vagina; to evaluate the effects on sperm
      subpopulations in the thawed samples of post mortem storage at room temperature
      and the addition of 20% of seminal plasma to the freezing extender and to
      correlate the percentage of subpopulations with gestation rate following
      artificial intrauterine insemination. The categorization of the subpopulations
      was based on sperm kinetic data from Computer Assisted Sperm Analysis (CASA). A
      hundred ewes were inseminated with thawed spermatozoa and gestation rate was
      correlated with the proportions of each subpopulation using Pearson correlation
      matrix and linear regression. Three distinct subpopulations were identified in
      the thawed samples of either ovine ejaculate collected in artificial vaginas (AV)
      or ovine spermatozoa retrieved from the cauda epididymis. Subpopulation 1 (SP1)
      was characterized by spermatozoa with slow and non-linear motion, subpopulation 2
      (SP2) was classified as hyperactived spermatozoa and subpopulation 3 (SP3) was
      composed of spermatozoa with fast, linear motion. The largest subpopulation in
      all groups was SP1. The semen collected in an artificial vagina had a higher
      (P<0.05) percentage of SP2 and lower (P<0.05) percentage of SP1 when compared to
      spermatozoa recovered after death. Increasing time of storage after death had a
      detrimental effect on sperm samples, increasing (P<0.05) the percentage of SP1
      and decreasing (P<0.05) SP2. Length of storage after death was the only variable
      that influenced, with an inversely proportional relationship, SP3. In samples
      stored for 48h after death no SP3 spermatozoa were present. The addition of
      seminal plasma to the cryopreservative decreased (P<0.05) the subpopulation of
      hyperactived spermatozoa (SP2). We conclude that, after thawing there are three
      sperm subpopulations in the spermatozoa obtained from the cauda epididymides and
      the semen collected in AVs and that the relative proportions of these
      subpopulations varies with the time of storage post mortem and the presence of
      20% of seminal plasma in the extender. However, we conclude that these
      subpopulations do not correlate with fertility after intrauterine artificial
      insemination.

PMID- 29029875
TI  - Oxytocin is not involved in luteolysis and early maternal recognition of
      pregnancy (MRP) in alpacas.
AB  - Pregnancy maintenance depends on the maternal recognition of pregnancy (MRP), a
      physiological process by which the lifespan of the corpus luteum is prolonged.
      This mechanism is not well characterized in camelids. The objectives of the
      present research were to determine if exogenous oxytocin prolongs the corpus
      luteum activity in alpacas and to evaluate expression and localization of
      oxytocin receptors within the endometrium at 9 and 14days post-mating. In the
      oxytocin studies, plasma progesterone profiles were determined after ovulation in
      the same alpacas on 2 cycles: one cycle without oxytocin treatment and one cycle
      with oxytocin treatment. Oxytocin was administered daily by intramuscular
      injections (IM) at a dose of 20IU (experiment 1, n=6) or 60IU (experiment 2, n=7
      from day 3 through day 10 after induction of ovulation with GnRH IM. There was no
      significant difference in the length of the luteal phase (i.e. corpus luteum
      lifespan) between the treated and control cycles using either 20 or 60IU of
      oxytocin. In the final experiment, uteri from open and pregnant alpacas (n=4 per
      group) at 9 and 14days post-mating were evaluated for expressions of oxytocin
      receptors by immunohistochemistry. No significant difference (P<=0.05) in the
      expression of oxytocin receptors was observed between open and pregnant animals
      in either staining intensity or tissue localization. We conclude that oxytocin is
      not involved in luteolysis and early MRP in alpacas.

PMID- 29029876
TI  - "Hidden" nephropathy after oral phosphate preparation to colonoscopy.

PMID- 29029877
TI  - Substitutions of S101 decrease proton and hydride transfers in the oxidation of
      betaine aldehyde by choline oxidase.
AB  - Choline oxidase oxidizes choline to glycine betaine, with two flavin-mediated
      reactions to convert the alcohol substrate to the carbon acid product. Proton
      abstraction from choline or hydrated betaine aldehyde in the wild-type enzyme
      occurs in the mixing time of the stopped-flow spectrophotometer, thereby
      precluding a mechanistic investigation. Mutagenesis of S101 rendered the proton
      transfer reaction amenable to study. Here, we have investigated the aldehyde
      oxidation reaction catalyzed by the mutant enzymes using steady-state and rapid
      kinetics with betaine aldehyde. Stopped-flow traces for the reductive half
      reaction of the S101T/V/C variants were biphasic, corresponding to the reactions
      of proton abstraction and hydride transfer. In contrast, the S101A enzyme yielded
      monophasic traces like wild-type choline oxidase. The rate constants for proton
      transfer in the S101T/C/V variants decreased logarithmically with increasing
      hydrophobicity of residue 101, indicating a behavior different from that seen
      previously with choline for which no correlation was determined. The rate
      constants for hydride transfer also showed a logarithmic decrease with increasing
      hydrophobicity at position 101, which was similar to previous results with
      choline as a substrate for the enzyme. Thus, the hydrophilic character of S101 is
      necessary not only for efficient hydride transfer but also for the proton
      abstraction reaction.

PMID- 29029878
TI  - Dielectric properties of plasma membrane: A signature for dyslipidemia in
      diabetes mellitus.
AB  - Dielectric properties of a living biological membrane play crucial role
      indicating the status of the cell in pathogenic or healthy condition. A distinct
      variation in membrane capacitance and impedance was observed for peripheral blood
      mononuclear cell (PBMC) suspensions for diabetic and diabetic-dyslipidemic
      subjects compared to healthy control. Low frequency region were explicitly
      considered in electrical analysis to address complex membrane dielectric factors
      that alter the system capacitance of a PBMC suspension. Such variation was marked
      in size, morphology and membrane function of PBMCs for control and diseased
      cases. Scanning electron microscopy (SEM) and atomic force microscopy (AFM)
      studies reveal significant alteration in surface morphology of PBMCs in diseased
      condition. Side scatter of flow cytometry reveals complexity of PBMCs in diseased
      condition. Changes in size between groups were not found by SEM and forward
      scatter. Functional alteration in PBMCs was manifested by significant changes in
      cell membrane properties like Na+, K+ ATPase and Ca2+, Mg2+ ATPase activity,
      reduced plasma membrane fluidity and changes in intracellular Ca2+ content, which
      bear significant correlation in diabetic and diabetic dyslipidemic subjects.
      Therefore, dielectric parameters of PBMCs in diabetic-dyslipidemic challenges may
      led to interesting correlation opening the possibility of identifying crucial
      signature biomarkers.

PMID- 29029879
TI  - Reduced renal function in patients with Myotonic Dystrophy type 1 and the
      association to CTG expansion and other potential risk factors for chronic kidney
      disease.
AB  - Myotonic dystrophy type 1 (DM1) affects several organs. Disease severity and age
      at onset are correlated to the CTG repeat expansion. The aim of this study was to
      assess renal function and the association to numbers of CTG repeat expansion in
      patients with DM1. Ninety-eight patients with DM1 were included. Glomerular
      filtration rate (measured GFR) was measured using iohexol clearance. Data on CTG
      repeats were available in 83/98 (85%) patients. The overall mGFR was 74 (16)
      ml/min/1.73 m2 (range 38-134). Sixty-four patients (69%) had a mild and sixteen
      patients (17%) a moderate decrease in renal function (mGFR 60-89 and 30-59
      ml/min/1.73 m2, respectively). No correlations were found between CTG repeats and
      mGFR (r = 0.10, p = 0.4) or between CTG repeats and serum cystatin C (r = 0.12, p
      = 0.29). CTG repeats was positively correlated to creatinine-based estimates of
      GFR (eGFR) (modified diet in renal disease r = 0.49, p < 0.001, CKD-EPI
      creatinine equation; r = 0.50, p < 0.001), but analyses using Structural Equation
      Modeling showed no correlation. The correlation was explained by an indirect
      effect via serum creatinine and skeletal muscle mass index. In conclusion,
      patients with DM1 seem to have a slight decrease in renal function but there is
      no association between renal function and the number of CTG repeats, a marker of
      disease severity.

PMID- 29029880
TI  - Open versus endovascular repair of ruptured abdominal aortic aneurysms: What have
      we learned after more than 2 decades of ruptured endovascular aneurysm repair?
AB  - BACKGROUND: Ruptured abdominal aortic aneurysm is one of the most difficult
      clinical problems in surgical practice, with extraordinarily high morbidity and
      mortality. During the past 23 years, the literature has become replete with
      reports regarding ruptured endovascular aneurysm repair. METHODS: A variety of
      study designs and databases have been utilized to compare ruptured endovascular
      aneurysm repair and open surgical repair for ruptured abdominal aortic aneurysm
      and studies of various designs from different databases have yielded vastly
      different conclusions. It therefore remains controversial whether ruptured
      endovascular aneurysm repair improves outcomes after ruptured abdominal aortic
      aneurysm in comparison to open surgical repair. RESULTS: The purpose of this
      article is to review the best available evidence comparing ruptured endovascular
      aneurysm repair and open surgical repair of ruptured abdominal aortic aneurysm,
      including single institution and multi-institutional retrospective observational
      studies, large national population-based studies, large national registries of
      prospectively collected data, and randomized controlled clinical trials.
      CONCLUSION: This article will analyze the study designs and databases utilized
      with their attendant strengths and weaknesses to understand the sometimes vastly
      different conclusions the studies have reached. This article will attempt to
      integrate the data to distill some of the lessons that have been learned
      regarding ruptured endovascular aneurysm repair and identify ongoing needs in
      this field.

PMID- 29029881
TI  - Comparison of self-gripping mesh and sutured mesh in open inguinal hernia repair:
      A meta-analysis of long-term results.
AB  - BACKGROUND: Complications after inguinal hernioplasty pose a significant burden
      on individual patients and society because of high numbers of repair procedures.
      Recently, the long-term results of a self-gripping ProGrip mesh for open inguinal
      hernia repair have become available. The aim of this meta-analyses was to compare
      these long-term results with the results of a Lichtenstein hernioplasty with a
      sutured mesh focusing on chronic pain, recurrence rate, foreign body sensation,
      and operation duration. METHODS: A systematic review of the literature was
      undertaken to identify randomized controlled trials comparing open inguinal
      hernia repair with a self-gripping ProGrip mesh and a conventional Lichtenstein
      hernioplasty. RESULTS: In the present meta-analysis, the outcomes of 10
      randomized controlled trials enrolling 2,541 patients were pooled. The mean
      follow-up was 24 months (range 6-72 months). There was no significant difference
      in the incidence of chronic pain (odds ratio = 0.93; 95% confidence interval,
      0.74-1.18), recurrence (odds ratio = 1.34; 95% confidence interval, 0.82-2.19),
      or foreign body sensation (odds ratio = 0.82; 95% confidence interval, 0.65
      1.03), between the self-gripping mesh and sutured mesh group at all follow-up
      time points. The mean operating time was significantly shorter (odds ratio = 
      7.58; 95% confidence interval, -9.58 to -5.58) in the self-gripping mesh group.
      CONCLUSION: The self-gripping mesh has comparable results with a sutured mesh
      regarding the incidence of chronic postoperative inguinal pain, recurrence and
      foreign body sensation. However, long-term results still are based on relatively
      small patient numbers and outcomes measures are heterogenic. The main advantage
      of the self-gripping mesh is the consistently significantly reduced operation
      time.

PMID- 29029882
TI  - Anesthetic considerations in a parturient with renal tubular acidosis and
      hypothyroidism undergoing cesarean delivery.
AB  - Renal tubular acidosis, associated with hypothyroidism, is rare. We present the
      case of a woman with known renal tubular acidosis and treated hypothyroidism who
      underwent emergency cesarean delivery under uneventful combined spinal-epidural
      anesthesia. The rationale for choosing the anesthetic technique and the potential
      risks associated with anesthesia and renal tubular acidosis are discussed.

PMID- 29029883
TI  - Brain sexual differentiation and effects of cross-sex hormone therapy in
      transpeople: A resting-state functional magnetic resonance study.
AB  - OBJECTIVES: It is hypothesized that transpeople show sex-atypical differentiation
      of the brain. Various structural neuroimaging studies provide support for this
      notion, but little is known about the sexual differentiation of functional
      resting-state networks in transpeople. In this study we therefore aimed to
      determine whether brain functional connectivity (FC) patterns in transpeople are
      sex-typical or sex-atypical, before and after the start of cross-sex hormone
      therapy (CHT). METHODS: We acquired resting-state functional magnetic resonance
      data in 36 transpeople (22 with female sex assigned at birth), first during
      gonadal suppression, and again four months after start of CHT, and in 37
      cisgender people (20 females), both sessions without any hormonal intervention.
      We used independent component analysis to identify the default mode network
      (DMN), salience network (SN), and left and right working memory network (WMN).
      These spatial maps were used for group comparisons. RESULTS: Within the DMN, SN,
      and left WMN similar FC patterns were found across groups. However, within the
      right WMN, cisgender males showed significantly greater FC in the right caudate
      nucleus than cisgender females. There was no such sex difference in FC among the
      transgender groups and they did not differ significantly from either of the
      cisgender groups. CHT (in transgender participants) and circulating sex steroids
      (in cisgender participants) did not affect FC. CONCLUSION: Our findings may
      suggest that cisgender males and females experience a dissimilar (early)
      differentiation of the right WMN and that such differentiation is less pronounced
      in transpeople.

PMID- 29029885
TI  - Cost-Effectiveness of Thoracic Radiation Therapy for Extensive-Stage Small Cell
      Lung Cancer Using Evidence From the Chest Radiotherapy Extensive-Stage Small Cell
      Lung Cancer Trial (CREST).
AB  - PURPOSE: The Chest Radiotherapy Extensive-Stage Small Cell Lung Cancer Trial
      (CREST) showed that adding thoracic radiation therapy (TRT) to the standard
      treatment (ST) paradigm of chemotherapy and prophylactic cranial irradiation
      improves overall survival and progression-free survival (PFS) in patients with
      extensive-stage small cell lung cancer (ES-SCLC). We evaluated the cost
      effectiveness of adding TRT to ST in ES-SCLC patients. METHODS AND MATERIALS: A
      cost-utility analysis was performed comparing TRT plus ST versus ST alone. The
      base-case time horizon was 24 months, consistent with the maximum PFS reported in
      the CREST. Overall survival was partitioned into 2 health states: PFS and
      postprogression survival. The proportion of patients in each health state over
      time was estimated by fitting parametric probability distributions to the CREST
      survival data. Costs were from a US health care payer perspective, and utilities
      were derived from the literature. Incremental cost-effectiveness ratios (ICERs)
      were calculated per quality-adjusted life-year (QALY) using a 3% discount rate.
      Sensitivity analyses addressed uncertainty in key variables. RESULTS: In the base
      case analysis, adding TRT to ST was both cost saving and more effective, thereby
      strongly dominating ST alone. At willingness-to-pay thresholds of $50,000/QALY,
      $100,000/QALY, and $200,000/QALY, TRT was preferred 68%, 81%, and 96% of the
      time, respectively. In the lifetime scenario analysis, the TRT ICER increased to
      $194,726/QALY. CONCLUSIONS: By use of the actual follow-up interval reported in
      the CREST, adding TRT to ST strongly dominates a strategy of ST alone in ES-SCLC
      patients. Since the long-term survival benefit of TRT is small relative to
      ongoing costs of progressive metastatic disease, we estimate less favorable ICERs
      for TRT over a lifetime horizon.

PMID- 29029884
TI  - Identification of ATIC as a Novel Target for Chemoradiosensitization.
AB  - PURPOSE: Mutations in the gene encoding 5-aminoimidazole-4-carboxamide
      ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), a bifunctional enzyme
      that catalyzes the final 2 steps of the purine de novo biosynthetic pathway, were
      identified in a subject referred for radiation sensitivity testing. Functional
      studies were performed to determine whether ATIC inhibition was radiosensitizing
      and, if so, to elucidate the mechanism of this effect and determine whether small
      molecule inhibitors of ATIC could act as effective radiosensitizing agents.
      METHODS AND MATERIALS: Both small interfering RNA knockdown and small molecule
      inhibitors were used to inactivate ATIC in cell culture. Clonogenic survival
      assays, the neutral comet assay, and gammaH2AX staining were used to assess the
      effects of ATIC inhibition or depletion on cellular DNA damage responses.
      RESULTS: Depletion of ATIC or inhibition of its transformylase activity
      significantly reduced the surviving fraction of cells in clonogenic survival
      assays in multiple cancer cell lines. In the absence of ionizing radiation
      exposure, ATIC knockdown or chemical inhibition activated cell cycle checkpoints,
      shifting cells to the more radiosensitive G2/M phase of the cell cycle, and
      depleted cellular adenosine triphosphate but did not result in detectable DNA
      damage. Cells in which ATIC was knocked down or inhibited and then treated with
      ionizing radiation displayed increased numbers of DNA double-strand breaks and a
      delay in the repair of those breaks relative to irradiated, but otherwise
      untreated, controls. Supplementation of culture media with exogenous adenosine
      triphosphate ameliorated the DNA repair phenotypes. CONCLUSIONS: These findings
      implicate ATIC as an effective, and previously unrecognized, target for
      chemoradiosensitization and, more broadly, suggest that purine levels in cells
      might have an underappreciated role in modulating the efficiency of DNA damage
      responses that could be exploited in radiosensitizing strategies.

PMID- 29029886
TI  - Heterogeneity in Treatment Response of Spine Metastases to Spine Stereotactic
      Radiosurgery Within "Radiosensitive" Subtypes.
AB  - PURPOSE: To characterize outcomes of metastatic colorectal and non-small cell
      lung cancer (NSCLC) histologies, compared with other radiosensitive histologies,
      treated with spine stereotactic radiosurgery with regard to local control,
      overall survival, and predictors of response. METHODS AND MATERIALS: A total of
      127 patients with 148 spine stereotactic radiosurgery-treated metastatic lesions
      at our institution between 2003 and 2013 were reviewed. We assessed clinical
      endpoints in relation to histologic type, including local control (LC) and
      overall survival (OS), using univariate and multivariate analyses. RESULTS: For
      all patients, the 1- and 2-year actuarial rates for LC were 82.6% and 75.8%, and
      rates for OS were 72.9% and 51.5% respectively. Among tumor histologies, 1-year
      cumulative incidence rates of local failure for thyroid, breast, lung, and colon
      cancer were 8.7%, 7.0%, 26.6%, and 39.6%, respectively. When analyzed together,
      NSCLC and colorectal cancers had significantly greater cumulative incidence rates
      at 1 and 2 years (30.4% and 38.7%, respectively) than other histologies (8.0% and
      14.1% respectively, P=.0008). Non-small cell lung cancer/colorectal tumor status
      was a significant predictor of local failure in a competing risk univariate model
      (hazard ratio 2.12, 95% confidence interval 1.07-4.17, P=.03) and multivariate
      model (hazard ratio 2.35, 95% confidence interval 1.12-4.92, P=.024).
      CONCLUSIONS: Spine stereotactic radiosurgery is an effective strategy in
      achieving local control of spine metastases, particularly among radiosensitive
      histologies. However, a subset of these classically defined histologies (NSCLC
      and colorectal) has a propensity toward local failure. In addition to resulting
      in poorer OS outcomes, the poor LC rates seen in NSCLC and colorectal cancers in
      this study are more consistent with a radioresistant phenotype, suggesting the
      need for optimized dosing regimens in this subgroup.

PMID- 29029887
TI  - Long-Term Clinical Safety of High-Dose Proton Radiation Therapy Delivered With
      Pencil Beam Scanning Technique for Extracranial Chordomas and Chondrosarcomas in
      Adult Patients: Clinical Evidence of Spinal Cord Tolerance.
AB  - PURPOSE: To assess the radiation dose tolerance of the spinal cord by reviewing
      our institutional experience regarding the incidence of radiation-induced spinal
      cord toxicity after high-dose pencil beam scanning proton therapy (PBSPT).
      METHODS AND MATERIALS: Seventy-six patients (median age 53 years; range, 23-79
      years) treated for spinal chordoma (n=55) or chondrosarcoma (n=21) met the
      following criteria and were retrospectively analyzed: PBSPT only, no
      reirradiation or concomitant chemotherapy, maximum dose (Dmax) to the spinal cord
      of >=45 Gy(relative biological effectiveness [RBE]), >=18 years of age, and
      follow-up of >=12 months. The delivered dose was 59.4 to 75.2 Gy(RBE) [median
      73.9 Gy(RBE)] delivered with conventional fractionation between 2000 and 2014.
      The Dmax, D2%, and V40-V60 of the surface (sSC) and center (cSC) of the spinal
      cord were recorded. Toxicity was scored according to the Common Terminology
      Criteria for Adverse Events, version 4.03. RESULTS: Median follow-up was 65.5
      months (range, 13-173 months). Patients received a mean Dmax and D2% to the sSC
      of 59.0 (median 58.7; range, 48.3-75.9) and 55.3 (median 52.7; range, 43.1-73.8)
      Gy(RBE), respectively. The corresponding values for the cSC were 52.3 (median
      52.7; range, 32.3-73.3) and 51.1 (median 52.0; range, 25.3-73.1) Gy(RBE),
      respectively. Four patients (5%) developed acute radiation-induced neurotoxicity
      (grade [G] 1, n=1; G2, n=3). Twelve patients (16%) experienced late neurologic
      toxicities (G1, n=7; G2, n=4; G4, n=1). One patient with a history of pre-PBSPT
      symptomatic spinal cord compression redeveloped tetraplegia (G4) after receiving
      a Dmax of 57.8 Gy(RBE) to the sSC and 54.1 Gy(RBE) to the cSC. No significant
      correlation was found between sSC Dmax and D2%, cSC Dmax and D2%, or the length
      of CTV and toxicity. CONCLUSIONS: High-dose conformal PBSPT may be delivered
      safely in close proximity to the spinal cord with minimal neurotoxicity. Dose
      constraints of 64 Gy(RBE) as D2% for the sSC and 54 Gy(RBE) for the cSC seem
      appropriate for clinical use.

PMID- 29029888
TI  - Reirradiation Using Permanent Interstitial Brachytherapy: A Potentially Durable
      Technique for Salvaging Recurrent Pelvic Malignancies.
AB  - PURPOSE: To present a time-to-failure (TTF) analysis for all patients treated
      with permanent interstitial brachytherapy (PIB) at our institution, with
      additional analyses to correlate successful reirradiation and to identify the
      frequency of severe grade 3 to 4 toxicity. METHODS AND MATERIALS: Forty-two
      previously irradiated patients received curative or palliative intent PIB for a
      recurrent pelvic malignancy between January 2009 and August 2016. Minimum follow
      up was 6 months after the PIB procedure. All patients had a biopsy-proven
      recurrence and were treated using PIB alone (n=32) or in combination with a short
      course of additional radiation therapy (n=10). Competing risk analyses were
      performed to assess the risk of failures in the presence of death without
      failure. Exploratory analyses were performed for factors related to failure using
      competing risk analyses and the Gray statistic. RESULTS: A total of 61 PIB
      implants were performed among 42 patients with a median follow-up of 16.3 months.
      Fifty-two implants were performed as the first salvage reirradiation to a
      solitary recurrence (8 patients had more than 1 lesion); the success rate for
      initial reirradiation using PIB was 73% (38 cases out of 52), and the median TTF
      was not reached. Nine patients underwent a second repeat PIB to the same
      recurrence as a form of salvage; 3 (33%) remain without evidence of recurrence.
      The median TTF after second salvage was 7.7 months. Even with the limited sample
      size, prolonged TTF was marginally associated with definitive intent (P=.07) and
      the extent of disease at the time of PIB (P=.08). Grade 3+ toxicities were seen
      in 8 patients (16.7%). CONCLUSIONS: Permanent interstitial brachytherapy is a
      feasible and potentially durable treatment modality that can be used to
      curatively salvage selected recurrent pelvic malignancies in a previously
      irradiated field.

PMID- 29029889
TI  - Brachytherapy for Intermediate-Risk Prostate Cancer, Androgen Deprivation, and
      the Risk of Death.
AB  - PURPOSE: To determine whether the use of 6 months' adjuvant androgen deprivation
      therapy (ADT) combined with brachytherapy for intermediate-risk (IR) and low-risk
      (LR) prostate cancer is associated with an increased risk of cardiovascular
      death. METHODS AND MATERIALS: This is a retrospective analysis of prospectively
      collected data from men treated in the British Columbia Cancer Agency
      brachytherapy program from 1998 to 2012. Men were categorized by risk group and
      ADT use. Cardiac and other comorbidities were recorded and compared between
      groups. Biochemical control (Phoenix definition, nadir + 2 ng/mL) was
      ascertained. Overall, prostate, cardiac, and other-cause mortality were analyzed
      by the Kaplan-Meier method and Fine and Gray competing-risk analysis. RESULTS:
      The study included 3155 men (1142 with LR cancer and 2013 with IR cancer) who
      have been followed up for a median of 7.9 years. ADT was received by 47% of IR
      patients and 37% of LR patients for a median of 6 months. Men with IR cancer were
      older and had more cardiac and other comorbidities than LR cases (P<.01).
      Biochemical control improved from 86% to 89% at 10 years with the use of ADT
      (P=.006). Overall survival was inferior in patients receiving ADT (84% vs 86% at
      10 years, P=.0274), and on competing-risk analysis, cardiovascular mortality in
      patients receiving ADT was higher in IR cases, 5.2% versus 3.6% at 10 years
      (P=.0493), but not in LR cases. Multivariate analysis confirmed increased cardiac
      mortality in IR patients receiving ADT (hazard ratio, 1.95 [95% confidence
      interval, 1.15-3.34]; P=.014). CONCLUSIONS: ADT adds little meaningful benefit in
      terms of biochemical control for IR men treated with low-dose-rate brachytherapy
      but likely decreases overall survival because of increased cardiac mortality. IR
      patients were older and had more cardiac risk factors than LR prostate cases;
      this may be because of a screening effect, case selection, or common etiologic
      cause.

PMID- 29029891
TI  - Imaging Findings Within the First 12 Months of Hepatocellular Carcinoma Treated
      With Stereotactic Body Radiation Therapy.
AB  - PURPOSE: To correlate the imaging findings of treated hepatocellular carcinoma
      (HCC) after stereotactic body radiation therapy (SBRT) with explant pathology and
      alpha-fetoprotein (AFP) response. METHODS AND MATERIALS: From 2007 to 2015, of
      146 patients treated with liver SBRT for Barcelona Clinic Liver Cancer stage A
      hepatocellular carcinoma, 10 were identified with inclusion criteria and had
      regular interval follow-up magnetic resonance imaging/triple phase computed
      tomography and explant pathology or declining AFP values for radiology-pathology
      response correlation. Reference standards for successful response were >90%
      necrosis on explant pathology or pretreatment AFP >75 ng/mL normalizing to <10
      ng/mL within 1 year after SBRT without other treatment. Subjects were treated
      with 24 to 50 Gy in 3 to 5 fractions. Multiphasic magnetic resonance imaging or
      computed tomography performed at 3, 6, 9, and 12 months after SBRT was compared
      with pretreatment imaging by 2 expert radiologists. Descriptive statistics were
      calculated. RESULTS: There were 10 subjects with 10 treated HCCs, classified as 3
      Organ Procurement and Transplantation Network (OPTN) 5a, 4 OPTN 5b, and 3 OPTN
      5x. All had successfully treated HCCs, according to explant pathology or
      declining AFP. Four of 10 HCCs had persistent central arterial hyperenhancement 3
      to 12 months after SBRT; persistent wash-out was common up to 12 months (9 of
      10). Of 10 treated HCCs, 9 exhibited decreased size at 12 months. Liver
      parenchyma adjacent to the lesion showed early (3-6 months) hyperemia followed by
      late (6-12 months) capsular retraction and delayed enhancement. No patient had a
      significant decline in liver function. CONCLUSIONS: In the absence of increasing
      size, persistent central arterial hyperenhancement and wash-out can occur within
      the first 12 months after SBRT in successfully treated HCCs and may not represent
      residual viable tumor. Liver parenchyma adjacent to the treated lesion showed
      inflammation followed by fibrosis, without significant change in hepatic
      function. Until a radiologic signature of tumor control is determined, freedom
      from local progression seems to be the best measure of HCC control after SBRT.

PMID- 29029893
TI  - The prevalence of sarcopenia is markedly increased in patients with intestinal
      failure and associates with several risk factors.
AB  - BACKGROUND & AIMS: Intestinal insufficiency and intestinal failure are conditions
      associated with malabsorption of micro- and macronutrients. Consequently,
      malnutrition and ensuing alterations in body composition are common in this
      context and patients may have an increased risk of progressive loss of skeletal
      muscle mass and function (i.e. sarcopenia). We investigated the prevalence of
      sarcopenia in patients with intestinal insufficiency and intestinal failure and
      identified associated risk factors. METHODS: This was a cross-sectional study
      including 113 clinically stable outpatients with intestinal insufficiency or
      intestinal failure. Body composition was assessed using bioelectrical impedance
      analysis and muscle function (strength or performance) using a handheld
      dynamometer and a timed up-and-go test. Sarcopenia was classified using the
      European Working Group on Sarcopenia in Older People criteria. Several
      parameters, including smoking, alcohol, and concurrent morbidities, were analyzed
      for association with sarcopenia. RESULTS: The prevalence of sarcopenia was 53.1%
      (95% CI; 43.8 to 62.2) in the combined patient group. In patients with intestinal
      failure the prevalence of sarcopenia was 72.7% (95% CI; 59.3 to 83.0) compared to
      34.5% (95% CI; 23.3 to 47.8) in those with intestinal insufficiency (OR 5.07 [95%
      CI; 2.27 to 11.31]; p < 0.001). Excessive alcohol consumption (OR 7.69 [95% CI;
      1.50 to 39.34]; p = 0.014), intestinal failure (OR 4.16 [95% CI; 1.69 to 10.28];
      p = 0.002), and inflammatory activity (OR 3.83 [95% CI; 1.06 to 12.84]; p =
      0.041), were identified as independent risk factors of sarcopenia. A trend was
      observed for hypermetabolism in multivariate analysis (OR 7.55 [95% CI; 0.79 to
      72.03]; p = 0.079). CONCLUSIONS: Patients with intestinal insufficiency and
      intestinal failure are at immense risk of developing sarcopenia. Associated risk
      factors are excessive alcohol consumption, intestinal failure, and inflammatory
      activity.

PMID- 29029892
TI  - The expert's guide to mealtime interventions - A Delphi method survey.
AB  - BACKGROUND: Prevalence of malnutrition and a myriad of barriers to adequate oral
      diet in hospitalised patients warrants further investment to improve the patient
      mealtime experience. The aim of this study was to explore barriers and enablers
      to implementing effective mealtime interventions and develop a process framework
      to guide clinicians and researchers in the area. MATERIALS AND METHODS: Potential
      experts in the area of hospital mealtime intervention were identified as having
      published in this field of work within the Australasian setting. Further
      information was sought by email and telephone communication on professional
      background; research experience; interest; and capacity to participate. Recruited
      participants were surveyed using a modified Delphi method to establish opinion
      and experience in the area of mealtime interventions. Results were collated and
      content was coded using a thematic analysis approach by the primary researcher
      and two additional reviewers. RESULTS: Thirty-two Australian authors in the area
      of mealtime interventions within the hospital environment were identified from
      publication. Twenty-one participants were able to be contacted and nineteen of
      these consented to enrol in the study. Participants included those from a
      dietetic (n = 14), nursing (n = 4) and medical (n = 1) background. Participants
      were deemed to have expert knowledge if they had significant involvement in the
      published research and demonstrated a deep level of understanding of hospital
      mealtime interventions. All participants provided key insights into barriers to
      oral intake in the hospital environment and suggestions for interventions to
      address these barriers. From the survey, an eight step framework to guide
      mealtime interventions was developed. CONCLUSION: Hospital mealtime interventions
      are complex processes. Interventions should be implemented after careful
      consideration of the local context and baseline data; and tailored to address
      barriers. Roles and responsibilities for nutrition care should be clear and
      consistent. Implementation planning is recommended to ensure that an ongoing
      process is in place to engage executive support and staff involvement, foster
      project team resilience and ensure sustainability of interventions.

PMID- 29029890
TI  - Radiation Therapy Deficiencies Identified During On-Site Dosimetry Visits by the
      Imaging and Radiation Oncology Core Houston Quality Assurance Center.
AB  - PURPOSE: To review the dosimetric, mechanical, and programmatic deficiencies most
      frequently observed during on-site visits of radiation therapy facilities by the
      Imaging and Radiation Oncology Core Quality Assurance Center in Houston (IROC
      Houston). METHODS AND MATERIALS: The findings of IROC Houston between 2000 and
      2014, including 409 institutions and 1020 linear accelerators (linacs), were
      compiled. On-site evaluations by IROC Houston include verification of absolute
      calibration (tolerance of +/-3%), relative dosimetric review (tolerances of +/-2%
      between treatment planning system [TPS] calculation and measurement), mechanical
      evaluation (including multileaf collimator and kilovoltage-megavoltage isocenter
      evaluation against Task Group [TG]-142 tolerances), and general programmatic
      review (including institutional quality assurance program vs TG-40 and TG-142).
      RESULTS: An average of 3.1 deficiencies was identified at each institution
      visited, a number that has decreased slightly with time. The most common errors
      are tabulated and include TG-40/TG-142 compliance (82% of institutions were
      deficient), small field size output factors (59% of institutions had errors
      >=3%), and wedge factors (33% of institutions had errors >=3%). Dosimetric errors
      of >=10%, including in beam calibration, were seen at many institutions.
      CONCLUSIONS: There is substantial room for improvement of both dosimetric and
      programmatic issues in radiation therapy, which should be a high priority for the
      medical physics community. Particularly relevant was suboptimal beam modeling in
      the TPS and a corresponding failure to detect these errors by not including TPS
      data in the linac quality assurance process.

PMID- 29029894
TI  - Clemastine fumarate for promotion of optic nerve remyelination.

PMID- 29029895
TI  - Double-duty solutions for the double burden of malnutrition.

PMID- 29029896
TI  - Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD):
      a randomised, controlled, double-blind, crossover trial.
AB  - BACKGROUND: Multiple sclerosis is a degenerative inflammatory disease of the CNS
      characterised by immune-mediated destruction of myelin and progressive
      neuroaxonal loss. Myelin in the CNS is a specialised extension of the
      oligodendrocyte plasma membrane and clemastine fumarate can stimulate
      differentiation of oligodendrocyte precursor cells in vitro, in animal models,
      and in human cells. We aimed to analyse the efficacy and safety of clemastine
      fumarate as a treatment for patients with multiple sclerosis. METHODS: We did
      this single-centre, 150-day, double-blind, randomised, placebo-controlled,
      crossover trial (ReBUILD) in patients with relapsing multiple sclerosis with
      chronic demyelinating optic neuropathy on stable immunomodulatory therapy.
      Patients who fulfilled international panel criteria for diagnosis with disease
      duration of less than 15 years were eligible. Patients were randomly assigned
      (1:1) via block randomisation using a random number generator to receive either
      clemastine fumarate (5.36 mg orally twice daily) for 90 days followed by placebo
      for 60 days (group 1), or placebo for 90 days followed by clemastine fumarate
      (5.36 mg orally twice daily) for 60 days (group 2). The primary outcome was
      shortening of P100 latency delay on full-field, pattern-reversal, visual-evoked
      potentials. We analysed by intention to treat. The trial is registered with
      ClinicalTrials.gov, number NCT02040298. FINDINGS: Between Jan 1, 2014, and April
      11, 2015, we randomly assigned 50 patients to group 1 (n=25) or group 2 (n=25).
      All patients completed the study. The primary efficacy endpoint was met with
      clemastine fumarate treatment, which reduced the latency delay by 1.7 ms/eye (95%
      CI 0.5-2.9; p=0.0048) when analysing the trial as a crossover. Clemastine
      fumarate treatment was associated with fatigue, but no serious adverse events
      were reported. INTERPRETATION: To our knowledge, this is the first randomised
      controlled trial to document efficacy of a remyelinating drug for the treatment
      of chronic demyelinating injury in multiple sclerosis. Our findings suggest that
      myelin repair can be achieved even following prolonged damage. FUNDING:
      University of California, San Francisco and the Rachleff Family.

PMID- 29029898
TI  - Department of Error.

PMID- 29029899
TI  - Bite it forward ... bite it better? Incisor procumbency and mechanical advantage
      in the chisel-tooth and scratch-digger genus Ctenomys (Caviomorpha, Rodentia).
AB  - The subterranean genus Ctenomys (~60 species, ~100-1000g) constructs its burrows
      by using both forefeet and teeth throughout a wide range of habitats in South
      America. They show a high variation in the incisors' angle of attack
      (procumbency) and a mostly conserved skull morphology, not only amongst their
      congeners, but within the caviomorph rodents. Traditionally, procumbency has been
      largely related to tooth-digging. Looking for the possible influence of incisor
      procumbency on the mechanical advantage (MA) of each of the seven jaw adductor
      muscles in the genus, we examined 165 skulls representing 24 species. We also
      evaluated the role of two other relevant traits - i.e. mandibular width and
      diastema length - in jaw biomechanics and the existence of a relationship between
      procumbency angle and soil hardness. The in- and out-lever arms (Li and Lo) of
      the involve muscles were determined based on their insertion's 3D-coordinates and
      integrated to calculate their MA. Interspecific scaling relationships for skull
      and muscle measurements were analyzed through reduced major axis regression
      performed with phylogenetically independent standardized contrasts. Although the
      procumbency angle ranged between ~92.5 degrees  (C. mendocinus) and ~107.2 (C.
      occultus), we found that it was not significantly correlated with the MA of any
      jaw adductor muscle. This study also showed that the incisor procumbency
      variation was not associated with the relative rostral length or soil hardness.
      This result contradicts previous generalizations about a correlation between
      habitat conditions and the procumbency of the incisors in subterranean rodents.
      In sum, our results suggest that, within Ctenomys, possessing more procumbent
      incisors may not represent a biomechanical advantage, but might be beneficial in
      other aspects related to chisel-tooth digging or food processing behaviors.

PMID- 29029900
TI  - Teixobactin as a scaffold for unlimited new antimicrobial peptides: SAR study.
AB  - It looks that a new era of antimicrobial peptides (AMPs) started with the
      discovery of teixobactin, which is a "head to side-chain" cyclodepsipeptide. It
      was isolated from a soil gram-negative b-proteobacteria by means of a
      revolutionary technique. Since there, several groups have developed synthetic
      strategies for efficient synthesis of this peptide and its analogues as well.
      Herein, all chemistries reported as well as the biological activity of the
      analogues are analyzed. Finally, some inputs regarding new trends for the next
      generation of analogues are discussed.

PMID- 29029901
TI  - Spectrum of orocutaneous disease associations: Immune-mediated conditions.
AB  - There are a number of diseases that manifest both on the skin and the oral
      mucosa, and therefore the importance for dermatologists in clinical practice to
      be aware of these associations is paramount. In the following continuing medical
      education series, we outline orocutaneous disease associations with both
      immunologic and inflammatory etiologies.

PMID- 29029902
TI  - Spectrum of orocutaneous disease associations: Genodermatoses and inflammatory
      conditions.
AB  - The oral cavity and cutaneous organ systems share a close embryologic origin.
      Therefore, there are numerous dermatologic conditions presenting with concomitant
      oral findings of which the dermatologist must be aware. The second article in
      this continuing medical education series reviews inflammatory orocutaneous
      conditions and a number of genodermatoses. It is essential for dermatologists to
      be familiar with oral cavity manifestations associated with dermatologic diseases
      for prompt diagnosis, management, and appropriate referral to stomatology and
      dentistry.

PMID- 29029903
TI  - Folate and phototherapy: What should we inform our patients?
AB  - BACKGROUND: Ultraviolet (UV) degradation of folate has been studied in vitro and
      in vivo, but comprehensive reviews of the subject and recommendations for
      supplementing folate are lacking, especially for women of childbearing age, in
      whom decreases in folate predisposes newborns to neural tube defects. OBJECTIVE:
      We reviewed the effects of phototherapy on folate and provide a recommendation
      for women of childbearing age on phototherapy. METHODS: PubMed was searched for
      in vivo studies comparing folate levels before and after phototherapy. RESULTS:
      There is no evidence of decreased folate levels after UVA exposure. Decreased
      folate levels after sun exposure were limited to subjects taking folate
      supplements. Studies using narrowband UVB showed mixed results, potentially
      explained by dose-dependent degradation of folate; exposure >40 J/cm2
      cumulatively and >2 J/cm2 per treatment were associated with 19%-27% decreases in
      serum folate levels, while lower doses did not affect folate levels. LIMITATIONS:
      Extensive variability in results from studies and lack of considering
      confounders. CONCLUSIONS: We recommend all women of childbearing age on
      phototherapy take 0.8 mg/day of folate supplements, as suggested by current
      guidelines for women of childbearing age, to reduce the risk of neural tube
      defects in unplanned pregnancy.

PMID- 29029904
TI  - Incidental skin malignancies in teledermatology and in-person cohorts in the
      Veterans Affairs Health System.

PMID- 29029905
TI  - Perioperative complications with new oral anticoagulants dabigatran, apixaban,
      and rivaroxaban in Mohs micrographic surgery: A retrospective study.

PMID- 29029906
TI  - High prevalence of combination tanning among undergraduates: Survey at a
      southeastern US university.

PMID- 29029907
TI  - Acne, sexual orientation, and mental health among young adults in the United
      States: A population-based, cross-sectional study.

PMID- 29029908
TI  - Vancomycin and DRESS: A retrospective chart review of 32 cases in Los Angeles,
      California.

PMID- 29029909
TI  - Implementation of a dermatology teletriage system to improve access in an
      underserved clinic: A retrospective study.

PMID- 29029910
TI  - Assessment of dermatology clinic resources at safety-net hospitals: Results from
      a national survey.

PMID- 29029911
TI  - Oral tofacitinib monotherapy in Korean patients with refractory moderate-to
      severe alopecia areata: A case series.

PMID- 29029912
TI  - Prevalence of pediatric alopecia areata among 572,617 dermatology patients.

PMID- 29029913
TI  - Lack of an association between alopecia areata and visceral or hematopoietic
      cancers.

PMID- 29029914
TI  - Recurrence of genital aphthosis in girls: A retrospective analysis.

PMID- 29029915
TI  - Frequent skin examinations in patients with actinic keratoses: Ethical,
      financial, and moral implications.

PMID- 29029916
TI  - The specimen that did not survive processing: Ethical considerations pertaining
      to open disclosure.

PMID- 29029917
TI  - Dihydroxyacetone and sunless tanning: Knowledge, myths, and current
      understanding.

PMID- 29029918
TI  - The demand for skin biopsy from a patient with delusional parasitosis.

PMID- 29029919
TI  - The doll hairline: A clue for the diagnosis of frontal fibrosing alopecia.

PMID- 29029920
TI  - Mitigation or prevention of mild hair dye contact dermatitis after pretreatment
      with clobetasol foam.

PMID- 29029921
TI  - The modified purse-string suture: A useful technique for the repair of cutaneous
      surgical wounds.

PMID- 29029922
TI  - Submitting tangential nail-matrix specimens.

PMID- 29029923
TI  - Subcutaneous island flap on the nasal ala.

PMID- 29029924
TI  - Smoke-evacuating cautery pencils for dermatologic surgery.

PMID- 29029925
TI  - Does the dermatology standardized letter of recommendation alter applicants'
      chances of matching into residency?

PMID- 29029926
TI  - Comment on "Psychocutaneous disease: Clinical perspectives".

PMID- 29029927
TI  - Onychophagia and onychotillomania can be effectively managed.

PMID- 29029928
TI  - Recurrence, evolution, and re-excision of moderately dysplastic nevi.

PMID- 29029929
TI  - Approach to moderately dysplastic nevi with positive histologic margins.

PMID- 29029930
TI  - Histopathologic features of melanoma in difficult-to-diagnose lesions: A case
      control study; methodological issues.

PMID- 29029931
TI  - Reply to: "Histopathologic features of melanoma in difficult-to-diagnose lesions:
      A case-control study; methodological issues".

PMID- 29029932
TI  - Quantitative analysis of O-GlcNAcylation in combination with isobaric tag
      labeling and chemoenzymatic enrichment.
AB  - Protein O-GlcNAcylation regulates various biological processes, and is associated
      with several diseases. Therefore, the development of quantitative proteomics is
      important for understanding the mechanisms of O-GlcNAc-related diseases. We
      previously reported selective enrichment of O-GlcNAcylated peptides, which
      provided high-selectivity and effective release by a novel thiol-alkyne and thiol
      disulfide exchange. Here, we describe a new approach using initial isobaric tag
      labeling for relative quantification followed by enrichment and beta
      elimination/Michael addition with dithiothreitol for identification of both
      proteins and modification sites. The approach was validated using model proteins
      and peptides. This novel strategy could be used for quantitative O-GlcNAcome of
      biological samples.

PMID- 29029934
TI  - Ability of pulse wave transit time to detect changes in stroke volume and to
      estimate cardiac output compared to thermodilution technique in isoflurane
      anaesthetised dogs.
AB  - OBJECTIVE: To evaluate the ability of pulse wave transit time (PWTT) to detect
      changes in stroke volume (SV) and to estimate cardiac output (CO) compared with
      the thermodilution technique in isoflurane-anaesthetized dogs. STUDY DESIGN:
      Prospective, experimental study. ANIMALS: Eight adult laboratory dogs. METHODS:
      The dogs were anaesthetized with isoflurane and mechanically ventilated.
      Reference CO (TDCO) was measured via a pulmonary artery catheter using the
      thermodilution technique and reference SV (TDSV) was calculated. PWTT was
      calculated as the time from the electrocardiogram R-wave peak to the rise point
      of the pulse oximeter wave. Estimated CO (esCO) was derived from PWTT after
      calibration with arterial pulse pressure (both non-invasive and invasive methods)
      and TDCO. Haemodynamic changes were induced by administration of phenylephrine
      (vasoconstriction), high isoflurane (vasodilatation and negative inotropy) and
      dobutamine (vasodilatation and positive inotropy). Trending between percentage
      change in PWTT and TDSV was assessed using concordance analysis and receiver
      operator characteristic (ROC) curve. The agreement between esCO and TDCO was
      evaluated using the Bland-Altman method. RESULTS: The direction of percentage
      change between consecutive PWTT and the corresponding TDSV showed a concordance
      rate of 95%, with correlation coefficients of -0.86 (p<0.001). Area under the ROC
      curve for the change in PWTT to detect 15% change in TDSV was 0.91 (p<0.001).
      TDCO compared with esCO calibrated with invasive and non-invasive blood pressure
      showed a bias (precision of agreement) of 0.58 (1.54) and 0.57 (1.59) L minute-1
      with a percentage error of +/-61% and +/-63%, respectively. CONCLUSIONS AND
      CLINICAL RELEVANCE: In isoflurane-anaesthetized dogs, PWTT showed a good trending
      ability to detect 15% changes in SV. This technique is easy to use, inexpensive,
      non-invasive and could become routine anaesthetic monitoring. However, the
      agreement between absolute esCO and TDCO was unacceptable.

PMID- 29029933
TI  - Highly potent and selective NaV1.7 inhibitors for use as intravenous agents and
      chemical probes.
AB  - The discovery and selection of a highly potent and selective NaV1.7 inhibitor PF
      06456384, designed specifically for intravenous infusion, is disclosed. Extensive
      in vitro pharmacology and ADME profiling followed by in vivo preclinical PK and
      efficacy model data are discussed. A proposed protein-ligand binding mode for
      this compound is also provided to rationalise the high levels of potency and
      selectivity over inhibition of related sodium channels. To further support the
      proposed binding mode, potent conjugates are described which illustrate the
      potential for development of chemical probes to enable further target evaluation.

PMID- 29029897
TI  - Worldwide trends in body-mass index, underweight, overweight, and obesity from
      1975 to 2016: a pooled analysis of 2416 population-based measurement studies in
      128.9 million children, adolescents, and adults.
AB  - BACKGROUND: Underweight, overweight, and obesity in childhood and adolescence are
      associated with adverse health consequences throughout the life-course. Our aim
      was to estimate worldwide trends in mean body-mass index (BMI) and a
      comprehensive set of BMI categories that cover underweight to obesity in children
      and adolescents, and to compare trends with those of adults. METHODS: We pooled
      2416 population-based studies with measurements of height and weight on 128.9
      million participants aged 5 years and older, including 31.5 million aged 5-19
      years. We used a Bayesian hierarchical model to estimate trends from 1975 to 2016
      in 200 countries for mean BMI and for prevalence of BMI in the following
      categories for children and adolescents aged 5-19 years: more than 2 SD below the
      median of the WHO growth reference for children and adolescents (referred to as
      moderate and severe underweight hereafter), 2 SD to more than 1 SD below the
      median (mild underweight), 1 SD below the median to 1 SD above the median
      (healthy weight), more than 1 SD to 2 SD above the median (overweight but not
      obese), and more than 2 SD above the median (obesity). FINDINGS: Regional change
      in age-standardised mean BMI in girls from 1975 to 2016 ranged from virtually no
      change (-0.01 kg/m2 per decade; 95% credible interval -0.42 to 0.39, posterior
      probability [PP] of the observed decrease being a true decrease=0.5098) in
      eastern Europe to an increase of 1.00 kg/m2 per decade (0.69-1.35, PP>0.9999) in
      central Latin America and an increase of 0.95 kg/m2 per decade (0.64-1.25,
      PP>0.9999) in Polynesia and Micronesia. The range for boys was from a non
      significant increase of 0.09 kg/m2 per decade (-0.33 to 0.49, PP=0.6926) in
      eastern Europe to an increase of 0.77 kg/m2 per decade (0.50-1.06, PP>0.9999) in
      Polynesia and Micronesia. Trends in mean BMI have recently flattened in
      northwestern Europe and the high-income English-speaking and Asia-Pacific regions
      for both sexes, southwestern Europe for boys, and central and Andean Latin
      America for girls. By contrast, the rise in BMI has accelerated in east and south
      Asia for both sexes, and southeast Asia for boys. Global age-standardised
      prevalence of obesity increased from 0.7% (0.4-1.2) in 1975 to 5.6% (4.8-6.5) in
      2016 in girls, and from 0.9% (0.5-1.3) in 1975 to 7.8% (6.7-9.1) in 2016 in boys;
      the prevalence of moderate and severe underweight decreased from 9.2% (6.0-12.9)
      in 1975 to 8.4% (6.8-10.1) in 2016 in girls and from 14.8% (10.4-19.5) in 1975 to
      12.4% (10.3-14.5) in 2016 in boys. Prevalence of moderate and severe underweight
      was highest in India, at 22.7% (16.7-29.6) among girls and 30.7% (23.5-38.0)
      among boys. Prevalence of obesity was more than 30% in girls in Nauru, the Cook
      Islands, and Palau; and boys in the Cook Islands, Nauru, Palau, Niue, and
      American Samoa in 2016. Prevalence of obesity was about 20% or more in several
      countries in Polynesia and Micronesia, the Middle East and north Africa, the
      Caribbean, and the USA. In 2016, 75 (44-117) million girls and 117 (70-178)
      million boys worldwide were moderately or severely underweight. In the same year,
      50 (24-89) million girls and 74 (39-125) million boys worldwide were obese.
      INTERPRETATION: The rising trends in children's and adolescents' BMI have
      plateaued in many high-income countries, albeit at high levels, but have
      accelerated in parts of Asia, with trends no longer correlated with those of
      adults. FUNDING: Wellcome Trust, AstraZeneca Young Health Programme.

PMID- 29029935
TI  - Review: The relationship of hemoglobin A1c to postoperative surgical risk with an
      emphasis on joint replacement surgery.
AB  - Patients with diabetes mellitus are known to have a high risk of postoperative
      complications, including infections, impaired wound healing, cardiovascular
      events, venous thromboembolism, and mortality. Because hyperglycemia has been
      thought to mediate this risk, there is a clinical propensity for improving
      glycemic control, as assessed by hemoglobin A1c (HbA1c) level, prior to
      proceeding with elective surgery, particularly joint replacement surgery.
      However, it is not established whether chronic poor glycemic control, indicated
      by elevated HbA1c levels, predicts increased risk of postoperative complications.
      The benefit of improving glycemic control must be weighed against risks of
      delaying necessary elective surgery, such as joint replacement surgery, which
      risks may include negative impact on long-term glycemic control. Thus, we review
      the current evidence to determine the relationship between HbA1c and
      postoperative surgical risk, especially on joint replacement surgery.

PMID- 29029936
TI  - Excellence, Like Beauty, May Be in the Eyes of the Beholder.

PMID- 29029937
TI  - Neoadjuvant trials can accelerate research on novel systemic treatment modalities
      in cancer of the uterine cervix.

PMID- 29029938
TI  - Dengvaxia sensitizes seronegatives to vaccine enhanced disease regardless of age.
AB  - During a large scale clinical efficacy trial of the Sanofipasteur live-attenuated
      tetravalent dengue vaccine (Dengvaxia), features of hospitalized disease
      accompanying dengue infections in placebo recipients were closely similar to
      those in vaccinated children. However, the age specific hospitalization curves
      for these two populations differed. The curve for children vaccinated at ages 2
      16 years closely resembled the 1981 age specific hospitalization rate curve for
      Cuban children infected with DENV 2 who were sensitized by a prior DENV 1
      infection. The corresponding age specific hospitalization curve for placebos
      experiencing heterotypic secondary dengue infections peaked at age, 9-11 years.
      These differing epidemiological features support the conclusion that antibody
      dependent enhanced (ADE) dengue disease occurred in seronegatives who were
      sensitized by vaccine. As hospitalizations continue to occur in all age groups
      Dengvaxia consumers should be warned that sensitized vaccinated seronegatives
      will experience enhanced dengue disease into the forseeable future.

PMID- 29029940
TI  - Antibody-dependent phagocytosis (ADP) responses following trivalent inactivated
      influenza vaccination of younger and older adults.
AB  - Globally the most commonly utilised immunisation against influenza is the
      trivalent inactivated influenza vaccine (TIV) derived from an A/H1N1, an A/H3N2
      and aB type influenza virus. Vaccine effectiveness of TIV varies year to year,
      depending on how well antigenically matched the strains in the vaccine are
      compared to circulating strains [1,2]. Moreover, vaccine effectiveness can vary
      within certain subpopulations such as HIV-positive, young children and the
      elderly. Decreased vaccine effectiveness in the elderly is associated with
      impaired Ab production, as measured by standard hemagglutination inhibition (HAI)
      assays. We investigated the level of Antibody Dependent Phagocytosis (ADP)
      mediating Abs induced by the 2008-TIV in healthy Australian adults aged over and
      under 60years to determine if this immune function was also reduced in the
      elderly. We utilised an ADP assay that measures the uptake of IgG-opsonised HA
      coated fluorescent microspheres by a monocytic cell line. We also measured HA
      specific Abs that are close enough to bind to dimeric FcgammaRIIa ectodomains in
      an ELISA-based assay. Furthermore, we compared the extent of cross-reactive
      recognition of diverse influenza strains by ADP-mediating Abs found in pre- and
      post-vaccination sera in both of these groups. We found that young adults and
      older adults mounted similar ADP activity against HAs contained in the 2008-TIV,
      despite older adults have diminished HI responses. The level of cross-reactive
      antibodies against other HAs was limited in both groups. We conclude that
      seasonal influenza vaccination elicits limited cross-reactive ADP to HA in both
      young and older adults. New influenza vaccination strategies that elicit cross
      reactive and polyfunctional antibodies are needed.

PMID- 29029939
TI  - A novel therapeutic vaccine composed of a rearranged human papillomavirus type 16
      E6/E7 fusion protein and Fms-like tyrosine kinase-3 ligand induces CD8+ T cell
      responses and antitumor effect.
AB  - The development of cervical cancer is mainly caused by infection with high risk
      genotypes of human papillomavirus, particularly type 16 (HPV16), which accounts
      for more than 50% of cervical cancer. The two early viral oncogenes, E6 and E7,
      are continuously expressed in cervical cancer cells and are necessary to maintain
      the malignant cellular phenotype, thus providing ideal targets for immunotherapy
      of cervical cancer. In this study, a novel vaccine strategy was developed based
      on a rationally shuffled HPV16 E6/E7 fusion protein, the addition of Fms-like
      tyrosine kinase-3 ligand (Flt3L) or the N domain of calreticulin (NCRT), and the
      usage of a CpG adjuvant. Four recombinant proteins were constructed: m16E6E7
      (mutant E6/E7 fusion protein), rm16E6E7 (rearranged mutant HPV16 E6/E7 fusion
      protein), Flt3L-RM16 (Flt3L fused to rm16E6E7), and NCRT-RM16 (NCRT fused to
      rm16E6E7). Our results suggest that Flt3L-RM16 was the most potent of these
      proteins in terms of inducing E6- and E7-specific CD8+ T cell responses.
      Additionally, Flt3L-RM16 significantly induced regression of established E6/E7
      expressing TC-1 tumors. Higher doses of Flt3L-RM16 trended toward higher levels
      of antitumor activity, but these differences did not reach statistical
      significance. In summary, this study found that Flt3L-RM16 fusion protein is a
      promising therapeutic vaccine for immunotherapy of HPV16-associated cervical
      cancer.

PMID- 29029941
TI  - Timeliness of childhood vaccination in the Federated States of Micronesia.
AB  - BACKGROUND: Vaccination coverage is typically measured as the proportion of
      individuals who have received recommended vaccine doses by the date of
      assessment. This approach does not provide information about receipt of vaccines
      by the recommended age, which is critical for ensuring optimal protection from
      vaccine-preventable diseases (VPDs). OBJECTIVE: To assess vaccination timeliness
      in the Federated States of Micronesia (FSM), and the projected impact of
      suboptimal vaccination in the event of an outbreak. METHODS: Timeliness of the
      4th dose of diphtheria, tetanus, and acellular pertussis vaccine (DTaP) and 1st
      dose of measles, mumps, and rubella vaccine (MMR) among children 24-35 months was
      assessed in FSM. Both doses are defined as on time if administered from 361
      through 395 days in age. Timeliness was calculated by one-way frequency analysis,
      and dose delays, measured in months after recommended age, were described using
      inverse Kaplan-Meier analysis. A time-series susceptible-exposed-infected
      recovery (TSEIR) model simulated measles outbreaks in populations with on time
      and late vaccination. RESULTS: Total coverage for the 4th dose of DTaP ranged
      from 36.6% to 98.8%, and for the 1st dose of MMR ranged from 80.9% to 100.0%
      across FSM states. On time coverage for the 4th dose of DTaP ranged from 3.2% to
      52.3%, and for the 1st dose of MMR ranged from 21.1% to 66.9%. Maximum and median
      dose delays beyond the recommended age varied by state. TSEIR models predicted
      10.8-13.7% increases in measles cases during an outbreak based on these delays.
      CONCLUSIONS: In each of the FSM states, a substantial proportion of children
      received DTaP and MMR doses outside the recommended timeframe. Children who
      receive vaccinations later than recommended remain susceptible to VPDs during the
      period they remain unvaccinated, which may have a substantial impact on health
      systems during an outbreak. Immunization programs should consider vaccination
      timeliness in addition to coverage as a measure of susceptibility to VPDs in
      young children.

PMID- 29029942
TI  - Immunogenicity of aluminum-adsorbed hepatitis A vaccine (Havrix(r)) administered
      as a third dose after primary doses of Japanese aluminum-free hepatitis A vaccine
      (Aimmugen(r)) for Japanese travelers to endemic countries.
AB  - BACKGROUND: Hepatitis A vaccination is recommended for travelers to endemic
      countries. Several inactivated aluminum-adsorbed hepatitis A vaccines are
      available worldwide, but only one licensed hepatitis A vaccine is available in
      Japan. This vaccine is a lyophilized inactivated aluminum-free hepatitis A
      vaccine (Aimmugen(r)). The standard schedule of Aimmugen(r) is three doses (at 0,
      2-4 weeks, and 6 months). Japanese people will go abroad after receiving 2 doses
      of Aimmugen(r). Some long-term travelers will receive the third dose of hepatitis
      A vaccine at their destination, at 6-24 months after 2 doses of Aimmugen(r).
      Aimmugen(r) is not available in countries other than Japan. They receive
      inactivated aluminum-adsorbed hepatitis A vaccine instead of a third dose of
      Aimmugen(r). This study was undertaken to determine whether the booster
      vaccination with an aluminum-adsorbed hepatitis A vaccine is effective following
      two doses of Aimmugen(r). METHODS: Subjects were healthy Japanese adults aged 20
      years or older who had received two doses of Aimmugen(r). Subjects received a
      booster dose of Havrix(r)1440 intramuscularly as the third dose. Serology samples
      for hepatitis A virus antibody titers were taken 4-6 weeks later. Anti-hepatitis
      A virus antibody titers were measured by an inhibition enzyme-linked
      immunosorbent assay. RESULTS: Subjects were 20 healthy Japanese adults, 6 men and
      14 women. The mean age +/- standard deviation was 37.2 +/- 13.3. The
      seroprotection rate (SPR, anti-hepatitis A virus antibody titer >=10 mIU/mL) was
      85% at enrollment, and increased to 100% after vaccination with Havrix(r). The
      geometric mean anti-hepatitis A virus antibody titer increased from 39.8 mIU/mL
      to 2938.2 mIU/mL. CONCLUSION: The three scheduled doses consisting of two doses
      of Aimmugen(r) plus a third dose with Havrix(r) is more immunogenic than using
      only two doses of Aimmugen(r). The vaccination with Havrix(r) could be allowed to
      be used instead of a third dose of Aimmugen(r). (UMIN000009351).

PMID- 29029943
TI  - BCG immune activation reduces growth and angiogenesis in an in vitro model of
      head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent cancers
      worldwide and is associated with poor survival and significant treatment
      morbidity. The immune profile in patients with HNSCC is immunosuppressive and
      presents cytokine-mediated adaptive immune responses, triggered apoptosis of T
      cells, and alterations in antigen processing machinery. Bacille Calmette-Guerin
      (BCG) immunotherapy has been used successfully as a treatment for several types
      of cancer. In the present study, we sought to determine the antitumor effect of
      soluble mediators from peripheral blood mononuclear immune cells (PBMCs)
      activated with BCG vaccine in a three-dimensional coculture model of HNSCC growth
      using FaDu hypopharynx carcinoma squamous cells. BCG activation of PBMCs led to
      an increase in CD4+ and CD8+ lymphocyte subsets concomitant with an elevation in
      the levels of the antitumor cytokines IL-6, TNF-alpha and IFN-gamma, and a EGFR
      in FaDu cells. In addition, coculture with BCG-activated PBMCs reduced FaDu
      proliferation and increased cytotoxicity and apoptosis in parallel with an
      increase in caspase-3 activity and p53 expression. Finally, conditioned medium
      from BCG-activated PBMCs reduced the levels of the angiogenic factors vascular
      endothelial growth factor and angiopoietin-2 produced by human aortic endothelial
      cells (HAECs), and inhibited their proliferation and differentiation into
      capillary-like structures. Taken together, these results demonstrate that BCG
      vaccination induces antitumor responses in an HNSCC in vitro model and suggest
      that the BCG vaccine could be an effective alternative therapy for the treatment
      of HNSCC.

PMID- 29029944
TI  - [Antithrombotic treatment consensus protocol (anticoagulation and antiplatelet
      therapy) during the perioperative and periprocedural period in neurosurgery].
AB  - The use of antithrombotic medication (antiplatelet and/or anticoagulant therapy)
      is widespread. Currently, the management of neurosurgical patients receiving this
      type of therapy continues to be a problem of special importance. Patients
      receiving antithrombotic treatment may need neurosurgical care because of
      bleeding secondary to such treatment, non-haemorrhagic neurosurgical lesions
      requiring urgent attention, or simply elective neurosurgical procedures. In
      addition, the consequences of reintroducing early (bleeding or rebleeding) or
      late (thrombotic or thromboembolic) anticoagulation can be devastating. In this
      paper we present the antithrombotic treatment consensus protocol during the
      perioperative and periprocedural period, both in emergent surgery and in elective
      neurosurgical procedures.

PMID- 29029945
TI  - Continuous positive airway pressure improves sleep quality, but not glycaemic
      control, in patients with poorly controlled long-standing type 2 diabetes.

PMID- 29029946
TI  - Hypoglycaemia causes both daytime and nighttime QTc interval prolongation in
      patients with type 2 diabetes receiving insulin treatment.

PMID- 29029948
TI  - Erratum.

PMID- 29029947
TI  - A "Neurological Emergency Trolley" reduces turnaround time for high-risk
      medications in a general intensive care unit.
AB  - OBJECTIVES: To reduce medication turnaround times during neurological
      emergencies, a multidisciplinary team developed a neurological emergency crash
      trolley in our intensive care unit. This trolley includes phenytoin, hypertonic
      saline and mannitol, as well as other equipment. The aim of this study was to
      assess whether the cart reduced turnaround times for these medications. RESEARCH
      METHODOLOGY/DESIGN: In this retrospective cohort study, medication delivery times
      for two year epochs before and after its implementation were compared. Eligible
      patients were identified from our intensive care unit screening log. Adults who
      required emergent use of phenytoin, hypertonic saline or mannitol while in the
      intensive care unit were included. Groups were compared with nonparametric
      analyses. SETTING: 33-bed general medical-surgical intensive care unit in an
      academic teaching hospital. MAIN OUTCOME MEASURES: Time to medication
      administration. RESULTS: In the pre-intervention group, there were 43 patients
      with 66 events. In the post-intervention group, there were 45 patients with 80
      events. The median medication turnaround time was significantly reduced after
      implementation of the neurological emergency trolley (25 vs. 10minutes, p=0.003).
      There was no statistically significant difference in intensive care or 30-day
      survival between the two cohorts. CONCLUSION: The implementation of a novel
      neurological emergency crash trolley in our intensive care unit reduced
      medication turnaround times.

PMID- 29029949
TI  - Mitral Valve Replacement Using Carpentier-Edwards Pericardial Bioprosthesis in
      Patients With Rheumatic Heart Disease Aged Below 40 Years: 17-Year Results.
AB  - BACKGROUND: This study was designed to evaluate patients aged less than 40 years
      implanted with tissue heart valves with respect to survival, thromboembolism,
      structural degeneration and quality of life. METHODS: Between January, 2000 and
      December, 2016, 132 patients (51 males) with rheumatic heart disease underwent
      mitral valve replacement using Carpentier-Edwards, perimount, pericardial
      bioprostheses. The patients' ages ranged between 12 and 39 years (mean+/-SD
      30.12+/-5.51 years). RESULTS: The hospital and late mortality were 1.5% and 1.5%
      respectively. The total cumulative follow-up period was 1330.98 patient-years
      with a mean of 124.78+/-50.3 months (range, 1-204 months). The actuarial survival
      and actuarial event-free survival at 204 months was 96.9% (+/-0.01%) and 93.4%(+/
      0.03%) respectively. There was one episode of thromboembolism (0.32 events per
      100 patient years). Six (4.7%) patients underwent redo mitral valve replacement
      for severe bioprosthetic degeneration with stiffening and calcification using a
      Medtronic mechanical prosthesis (Medtronic Open Pivot, MN, USA). CONCLUSIONS: We
      conclude that Carpentier-Edwards perimount pericardial prosthesis provides
      satisfactory clinical performance in a young population with a low risk of
      degeneration and other valve-related events.

PMID- 29029950
TI  - Survival of Idiopathic Pulmonary Arterial Hypertension Patients in the Modern Era
      in Australia and New Zealand.
AB  - BACKGROUND: Epidemiology and treatment strategies continue to evolve in pulmonary
      arterial hypertension (PAH). We sought to define the characteristics and survival
      of patients with idiopathic, heritable and drug-induced PAH in the current
      management era. METHODS: Consecutive cases of idiopathic, heritable and drug
      induced PAH were prospectively enrolled into an Australian and New Zealand
      Registry. RESULTS: Between January 2012 and December 2016, a total of 220
      incident cases were enrolled (mean age 57.2+/-18.7years, female 69.5%) and
      followed for a median duration of 26 months (IQR17-39). Co-morbidities were
      common such as obesity (34.1%), systemic hypertension (30.5%), coronary artery
      disease (16.4%) and diabetes mellitus (19.5%). Initial combination therapy was
      used in 54 patients (dual, n=50; triple, n=4). Estimated survival rates at 1
      year, 2-years and 3-years were 95.6% (CI 92.8-98.5%), 87.3% (CI 82.5-92.4%) and
      77.0% (CI 70.3-84.3%), respectively. Multivariate analysis showed that male sex
      and lower 6-minute distance at diagnosis independently predicted worse survival,
      whereas obesity was associated with improved survival. Co-morbidities other than
      obesity did not impact survival. Initial dual oral combination therapy was
      associated with a trend towards better survival compared with initial oral
      monotherapy (adjusted HR=0.27, CI 0.06-1.18, p=0.082) CONCLUSIONS: The
      epidemiology and survival of patients with idiopathic PAH in Australia and New
      Zealand are similar to contemporary registries reported in Europe and North
      America. Male sex and poorer exercise capacity are predictive of mortality
      whereas obesity appears to exert a protective effect. Despite current therapies,
      PAH remains a life-threatening disease associated with significant early
      mortality.

PMID- 29029951
TI  - Intrahepatic Vgamma9Vdelta2 T-cells from HCV-infected patients show an exhausted
      phenotype but can inhibit HCV replication.
AB  - Hepatitis C virus (HCV) persistence results from inefficiencies of both innate
      and adaptive immune responses to eradicate the infection. A functional impairment
      of circulating Vgamma9Vdelta2 T-cells was described but few data are available on
      Vgamma9Vdelta2 T-cells in the liver that, however, represents the battlefield in
      the HCV/host interaction. Aim of this work was to compare circulating and
      intrahepatic Vgamma9Vdelta2 T-cells in chronic HCV-infected patients (HCVpos) and
      in HCV-negative (HCVneg) subjects. Phenotypic and functional analysis was
      performed by flow cytometry. Anti-HCV activity was analyzed by using an in vitro
      autologous liver culture system. Independently from HCV infection, the liver was
      enriched of Vgamma9Vdelta2 T-cells expressing an effector/activated phenotype. In
      contrast, an enrichment of PD-1 expressing Vgamma9Vdelta2 T-cells was observed
      both in the peripheral blood and in the liver of HCVpos patients, probably due to
      a persistent antigenic stimulation. Moreover, a lower frequency of IFN-gamma
      producing Vgamma9Vdelta2 T-cells was observed in the liver of HCVpos patients,
      suggesting a functional impairment in the cytokine production in HCVpos liver.
      Despite this hypo-responsiveness, intrahepatic Vgamma9Vdelta2 T-cells are able to
      exert an anti-HCV activity after specific stimulation. Altogether, our data show
      that HCV infection induced a dysregulation of intrahepatic Vgamma9Vdelta2 T cells
      that maintain their anti-HCV activity after specific stimulation. A study aimed
      to evaluate the mechanisms of the antiviral activity may be useful to identify
      new pathways able to improve Vgamma9Vdelta2 T-cells intrahepatic function during
      HCV infection.

PMID- 29029953
TI  - Acute calcific periarthritis in proximal interphalangeal joint: An unusual cause
      of acute finger pain.

PMID- 29029952
TI  - Survival Disparity Following Abdominal Aortic Aneurysm Repair Highlights
      Inequality in Ethnic and Socio-economic Status.
AB  - OBJECTIVES: Socio-economic status (SES) and ethnicity have been reported as
      markers influencing the likelihood of increased mortality. The aim of this study
      was to investigate how SES and ethnicity impacted patient survival after
      abdominal aortic aneurysm (AAA) repair. METHODS: Consecutive patients undergoing
      open and endovascular AAA repair during a 14.5 year period were identified.
      Ethnicity was defined as recorded on health records and SES (a score of 10, where
      1 is least deprived and 10 being most deprived) and was linked to census data.
      Operative outcomes were reported at 30 days and a medium-term survival analysis
      used the Cox model to report adjusted hazard ratios (HR). RESULTS: A total of
      6239 patients with a median age of 75 years and 78.7% males were included. The
      majority (5,654) were identified as New Zealand (NZ) Europeans, with 421
      identified as NZ Maori, 97 identified as belonging to a Pacific ethnic group, and
      67 identified as an Asian ethnic group. The median survival follow-up period was
      5 years and after adjusting for confounders, those who identified as NZ Maori had
      the lowest survival compared with all other ethnic groups with a HR of 1.46 (95%
      CI 1.23-1.72). Living in areas of high social deprivation >= 7 was an independent
      predictor of short and medium-term overall mortality when compared with living in
      deprivation deciles 1 or 2. CONCLUSIONS: Low SES was identified as a marker of
      risk for all ethnic groups in relation to both reduced short and medium-term
      survival. However, regardless of SES, NZ Maori had worse overall medium-term
      survival following AAA repair than the other ethnic groups. Therefore it appears
      that both SES and being Maori were markers of increased exposure to risk that
      negatively impact upon survival after AAA repair. There is a need to ensure
      systemic processes support initiatives that reduce this inequality.

PMID- 29029954
TI  - Cast immobilization of the lower-leg: No indication for thromboprophylactic
      therapy.

PMID- 29029955
TI  - Assessing incidence and risk factors of acute kidney injury in traumatic
      patients.

PMID- 29029956
TI  - Adipose stem cell neurospheres for Huntington's disease.

PMID- 29029957
TI  - A model-based approach for estimation of changes in lumbar segmental kinematics
      associated with alterations in trunk muscle forces.
AB  - The kinematics information from imaging, if combined with optimization-based
      biomechanical models, may provide a unique platform for personalized assessment
      of trunk muscle forces (TMFs). Such a method, however, is feasible only if
      differences in lumbar spine kinematics due to differences in TMFs can be captured
      by the current imaging techniques. A finite element model of the spine within an
      optimization procedure was used to estimate segmental kinematics of lumbar spine
      associated with five different sets of TMFs. Each set of TMFs was associated with
      a hypothetical trunk neuromuscular strategy that optimized one aspect of lower
      back biomechanics. For each set of TMFs, the segmental kinematics of lumbar spine
      was estimated for a single static trunk flexed posture involving, respectively,
      40 degrees  and 10 degrees  of thoracic and pelvic rotations. Minimum changes in
      the angular and translational deformations of a motion segment with alterations
      in TMFs ranged from 0 degrees  to 0.7 degrees  and 0 mm to 0.04 mm, respectively.
      Maximum changes in the angular and translational deformations of a motion segment
      with alterations in TMFs ranged from 2.4 degrees  to 7.6 degrees  and 0.11 mm to
      0.39 mm, respectively. The differences in kinematics of lumbar segments between
      each combination of two sets of TMFs in 97% of cases for angular deformation and
      55% of cases for translational deformation were within the reported accuracy of
      current imaging techniques. Therefore, it might be possible to use image-based
      kinematics of lumbar segments along with computational modeling for personalized
      assessment of TMFs.

PMID- 29029958
TI  - Innate Lymphoid Cell Regulation: Meeting the Long-Lost Cousin.
AB  - Innate lymphoid cells (ILCs) play critical roles in immune homeostasis and
      immunity to pathogens. Increasing evidence implicates dysregulated ILC responses
      as drivers of disease pathogenesis in multiple inflammatory disorders. A recent
      study reveals how inflammatory ILC responses can be suppressed by a newly defined
      subset of ILCs with regulatory function.

PMID- 29029959
TI  - LDT classification and therapeutic strategy of congenital body wall defects.
AB  - BACKGROUND: Repairing body wall defects is a critical step in the treatment of
      some congenital deformities, and this procedure may need the help from plastic
      surgeons. Although there are many articles about congenital deformities, body
      wall defects of these malformations are rarely studied as independent targets.
      METHODS: In this article, the authors present an LDT classification for
      congenital body wall defects according to the position of the defects, the tissue
      layers involved, and the surgical urgency, each of which is represented by
      letters L, D, and T, respectively. That is, the defects in different areas (L),
      full-thickness (D1), or partial (D0A, D0B) defects, defects needing instant
      repair (T2), semi-elective repair (T1), or elective repair (T0). Based on this
      classification system, the authors have performed body wall reconstruction on two
      pairs of thoraco-omphalopagus twins, one pair of ischiopagus tetrapus twins, and
      an infant and an adult, both of whom were diagnosed with pentalogy of Cantrell
      associated with ectopia cordis. RESULTS: Except for one pair of thoraco
      omphalopagus twins who died after emergency separation, all the other patients
      survived. Another pair of thoraco-omphalopagus twins suffered from wound
      dehiscence and partial flap necrosis, respectively, after surgery. An expanded
      polytetrafluoroethylene mesh in one sister of the ischiopagus twins was removed
      because of infection. CONCLUSIONS: LDT classification not only can help doctors
      categorise different congenital body wall defects rapidly and easily, but can
      also guide the reconstruction of these defects. It may have clinical value to
      plastic surgeons to some extent.

PMID- 29029960
TI  - Considerations for the correct interpretation of confidence intervals in nursing
      research.

PMID- 29029961
TI  - A critical analysis towards research perspectives: Reply to comments on "Modeling
      human behavior in economics and social science".
AB  - We take advantage of the challenging comments to the modeling approach we
      proposed in [35] to look ahead at a number of applications of the methods to the
      alternative questions these comments raise. In turn, our effort results in a
      number of interesting and valuable research perspectives. The presentation goes
      along three main lines. In the first line, we summarize briefly the aims and
      results in [35]. In the second section we give a technical the issues raised and,
      finally, the focus moves to the above mentioned research perspectives.

PMID- 29029962
TI  - Answering Schrodinger's question: A free-energy formulation.
AB  - The free-energy principle (FEP) is a formal model of neuronal processes that is
      widely recognised in neuroscience as a unifying theory of the brain and
      biobehaviour. More recently, however, it has been extended beyond the brain to
      explain the dynamics of living systems, and their unique capacity to avoid decay.
      The aim of this review is to synthesise these advances with a meta-theoretical
      ontology of biological systems called variational neuroethology, which integrates
      the FEP with Tinbergen's four research questions to explain biological systems
      across spatial and temporal scales. We exemplify this framework by applying it to
      Homo sapiens, before translating variational neuroethology into a systematic
      research heuristic that supplies the biological, cognitive, and social sciences
      with a computationally tractable guide to discovery.

PMID- 29029964
TI  - Corrigendum to "Avoidable cancer cases in the Nordic countries - The impact of
      overweight and obesity" [Eur J Cancer 79 (2017) 106-118].

PMID- 29029963
TI  - Genetic risk factors in Finnish patients with Parkinson's disease.
AB  - INTRODUCTION: Variation contributing to the risk of Parkinson's disease (PD) has
      been identified in several genes and at several loci including GBA, SMPD1, LRRK2,
      POLG1, CHCHD10 and MAPT, but the frequencies of risk variants seem to vary
      according to ethnic background. Our aim was to analyze how variation in these
      genes contributes to PD in the Finnish population. METHODS: The subjects
      consisted of 527 Finnish patients with early-onset PD, 325 patients with late
      onset PD and 403 population controls. We screened for known genetic risk variants
      in GBA, SMPD1, LRRK2, POLG1, CHCHD10 and MAPT. In addition, DNA from 225 patients
      with early-onset Parkinson's disease was subjected to whole exome sequencing
      (WES). RESULTS: We detected a significant difference in the length variation of
      the CAG repeat in POLG1 between patients with early-onset PD compared to
      controls. The p.N370S and p.L444P variants in GBA contributed to a relative risk
      of 3.8 in early-onset PD and 2.5 in late-onset PD. WES revealed five variants in
      LRRK2 and SMPD1 that were found in the patients but not in the Finnish ExAC
      sequences. These are possible risk variants that require further confirmation.
      The p.G2019S variant in LRRK2, common in North African Arabs and Ashkenazi Jews,
      was not detected in any of the 849 PD patients. CONCLUSIONS: The POLG1 CAG repeat
      length variation and the GBA p.L444P variant are associated with PD in the
      Finnish population.

PMID- 29029965
TI  - Contemporary Epidemiology, Management, and Outcomes of Patients Hospitalized for
      Heart Failure in China: Results From the China Heart Failure (China-HF) Registry.
AB  - BACKGROUND: Contemporary data on the epidemiology of heart failure (HF) in China
      are scarce. The China-HF Registry was designed to investigate clinical
      characteristics, management, and outcomes of patients hospitalized for HF in
      China. METHODS AND RESULTS: Data were collected prospectively on 13,687 patients
      with a primary discharge diagnosis of HF who were enrolled from 132 participating
      hospitals from January 2012 to September 2015. Data from the China-HF Registry
      was compared with previously published literature. The mean age was 65 +/- 15
      years, 59.1% were male, and 36.0% had preserved ejection fraction. Age, body mass
      index, and systolic blood pressure were lower than in high-income countries.
      Common comorbidities included hypertension (50.9%), coronary heart disease
      (49.6%), and atrial fibrillation (24.4%). The overall use of diuretics,
      angiotensin-converting enzyme inhibitors or angiotensin receptor blockers
      (ACEI/ARB), and beta-blockers at admission was 30.1%, 27.0%, and 25.6%,
      respectively, which was lower than in other registries. For patients discharged
      alive, ACEI/ARB, beta-blocker, and mineralocorticoid receptor antagonist use in
      patients with reduced ejection fraction was 67.5%, 70.0%, and 74.1%,
      respectively; device use was much lower. The median length of hospital stay was
      10 (range 7-15) days, and in-hospital mortality was 4.1 +/- 0.3%. Predictors of
      mortality included low systolic blood pressure, acute myocardial infarction,
      infection, right bundle branch block, and elevated total bilirubin and blood urea
      nitrogen level. CONCLUSIONS: Several important findings in patient profile and
      treatment patterns among Chinese patients with HF were noted compared with
      published literature. These data underscore the need for regional
      characterization of HF for global clinical trials and for the identification of
      several quality improvement opportunities.

PMID- 29029967
TI  - [10 years of external quality assurance in dialysis in Germany: Results and
      future prospects].
AB  - BACKGROUND: In 2006, the Federal Joint Committee introduced a quality assurance
      programme for ambulatory dialysis treatment in Germany. Regarding the impact of
      chronic dialysis treatment on the quality of life of patients and on health care
      costs, quality assurance in dialysis is considered highly relevant. The directive
      on Quality Assurance in Dialysis (QSD-RL) established an external quality
      assurance programme on the basis of the assessment of certain quality parameters
      combined with an internal quality management system based on benchmarking
      parameters in all dialysis practices and centres. Data on quality parameters are
      collected and analysed quarterly. Regional associations of statutory health
      insurance physicians take responsibility for quality improvement measures and
      sanctions. This article aims to provide an overview of the development of quality
      parameters from 2008 to 2015. METHODS: We analysed the summarised annual quality
      reports published on the website of the Federal Joint Committee between 2009 and
      2016. We present results on the so-called core quality parameters duration and
      frequency of dialysis sessions (both for haemodialysis patients), wKt/V for
      peritoneal dialysis patients, and percentage of haemodialysis patients with
      central venous catheters which has only been measured since 2014. RESULTS AND
      CONCLUSIONS: In 2015, 92,000 patients received outpatient dialysis. Between 2008
      and 2015, the results for the core quality parameters duration and frequency of
      haemodialysis improved while the results for wKt/V seemingly show an unfavourable
      trend. The percentage of patients with central venous catheters appears to be
      quite high, and thus indicates that there is potential for quality improvement.
      FUTURE PERSPECTIVES: For the future, the Federal Joint Committee has resolved to
      merge the quality assurance programmes in dialysis and in kidney transplantation
      into a newly designed programme that has the potential to follow patients through
      all stages and kinds of renal replacement therapy and to focus on further aspects
      of treatment quality.

PMID- 29029968
TI  - Linking Editorial / Anknupfungseditorial.

PMID- 29029966
TI  - Softening Among U.S. Smokers With Psychological Distress: More Quit Attempts and
      Lower Consumption as Smoking Drops.
AB  - INTRODUCTION: It has been argued that as smoking prevalence declines, the
      remaining smokers represent a "hard core" who are unwilling or unable to quit, a
      process known as hardening. However, as recently shown, the general smoking
      population is softening not hardening (i.e., as prevalence falls, more quit
      attempts and lower consumption among continuing smokers). People with
      psychological distress smoke more, so they may represent hard-core smokers.
      METHODS: Using cross-sectional time series analysis, in 2016-2017 changes in quit
      attempts and cigarette consumption were evaluated over 19 years among smokers
      with serious psychological distress (Kessler-6 score >=13) based on the National
      Health Interview Survey (1997-2015), controlling for sociodemographic variables.
      RESULTS: People with psychological distress had higher smoking prevalence and
      consumed more cigarettes/day than people without distress. The percentage of
      those with at least one quit attempt was higher among those with psychological
      distress. The increase in quit attempts over time was similar among smokers in
      each of the distress levels. For every 10 years, the OR of a quit attempt
      increased by a factor of 1.13 (95% CI=1.02, 1.24, p<0.05). Consumption declined
      by 3.35 (95% CI= -3.94, -2.75, p<0.01) cigarettes/day for those with serious
      psychological distress. CONCLUSIONS: Although smoking more heavily than the
      general population, smokers with psychological distress, like the general
      population, are softening over time. To improve health outcomes and increase
      health equity, tobacco control policies should continue moving all subgroups of
      smokers down these softening curves, while simultaneously incorporating
      appropriately tailored quitting help into mental health settings.

PMID- 29029969
TI  - Cross-year peer-assisted learning using the inverted ("flipped") classroom
      design: A pilot study in dentistry.
AB  - BACKGROUND: The inverted classroom model (ICM) represents a special combination
      of online and attendance learning. The implementation of the didactic concept of
      "peer-assisted learning" (PAL) within an ICM design has not yet been described in
      the literature for the field of restorative dentistry. OBJECTIVE: It was the goal
      of the present study to develop an ICM offering in a cross-year PAL format (ICM
      cyPAL), and then introduce and evaluate it. METHOD: The pilot project was
      conducted at the dental clinic at the Goethe University of Frankfurt/Main, where
      following its conceptual development and implementation with three consecutive
      cohorts of students in their first clinical semester (the sixth semester at
      university) the ICM-cyPAL offering was evaluated. Data on acceptance, tutor
      effectiveness, group interaction models and learning strategies were collected
      using an evaluative instrument. RESULTS: 121 students (tutees) participated in
      three cohorts. The response rate reached 98.3 %. In total, the offering was given
      an average rating of 6.97+/-1.93 (from 1 = unsatisfactory to 10 = excellent). As
      the tutees explained the attention that the tutors employed gave to the group was
      "just right" (4.65+/-1.04; where 1 = too controlling and 4 = just right to 7 =
      left the group on their own too long) and talked "just the right amount" (4.54+/
      0.95; where 1 = too much and 4 = just right to 7 = talked too little). The
      results for tutor effectiveness reached values between 3.26+/-0.94 and 3.78+/
      0.87; for the evaluation of group interaction models average values were obtained
      from 3.41+/-0.98 to 3.89+/-0.73 (on a Likert scale of 1 = do not at all agree to
      5 = completely agree). Concerning the surveyed learning strategies, the
      dimensions of "resource management" and "implementation of the learning
      materials" were given the highest and lowest rankings, respectively. CONCLUSION:
      The tutees' ratings of the newly developed and implemented ICM-cyPAL offering in
      the dental context were mainly positive. The thematic orientation of the
      structured training program needs to be optimized. The offering itself requires
      both a high degree of organization and solid financial and staffing resources.

PMID- 29029970
TI  - ?

PMID- 29029971
TI  - ?

PMID- 29029972
TI  - Development of indicators for a nationwide cross-sectoral quality assurance
      procedure for mental health care of patients with schizophrenia, schizotypal and
      delusional disorders in Germany.
AB  - PURPOSE: This paper describes the development of quality indicators for an
      external statutory and cross-sectoral quality assurance (QA) procedure in the
      context of the German health care system for adult patients suffering from
      schizophrenia, schizotypal and delusional disorders (F20-F29). METHODS:
      Indicators were developed by a modified RAND/UCLA Appropriateness Method with 1)
      the compilation of an indicator register based on a systematic literature search
      and analyses of health care claims data, 2) the selection of indicators by an
      expert panel that rated them for relevance and for feasibility regarding
      implementation. Indicators rated positive for both relevance and feasibility
      formed the final indicator set. RESULTS: 847 indicators were identified by
      different searches. Out of these, 56 were selected for the indicator register.
      During the formal consensus process the expert panel recommended another 45
      indicators so that a total of 101 indicators needed to be considered by the
      panel. Of these, 27 indicators rated both relevant and feasible were included in
      the final set of indicators: this set included 4 indicators addressing
      structures, 19 indicators addressing processes and 4 indicators addressing
      outcomes. 17 indicators of the set will be reported by hospitals and 8 by
      psychiatric outpatient facilities. Two indicators considered to be cross-sectoral
      will be reported by both sectors. DISCUSSION: F20-F29 and its treatment show some
      specific features which so far have not been addressed by any procedure within
      the statutory QA program of the German health care system. These features
      include: Schizophrenia and related disorders a) are potentially chronic
      conditions, b) are mainly treated in outpatient settings, c) require a multi
      professional treatment approach and d) are treated regionally in catchment areas.
      These specific features in combination with the peculiarities of some legal,
      political and organizational characteristics of the German health care system and
      its statutory QA program have strongly influenced the development of indicators.
      The result was a seemingly "imbalanced" set of indicators with a greater number
      of indicators for inpatient than for outpatient care despite the fact that
      clinical reality is otherwise. CONCLUSIONS: The circumstances of the German
      health care system that restricted the development of this cross-sectoral QA
      procedure addressing care for F20-F29 are also most likely to emerge with the
      development of cross-sectoral QA procedures for other (potentially) chronic
      conditions that are mainly treated in the outpatient setting by multi
      professional teams or by networks of different providers. In order to be able to
      develop a QA procedure that mirrors the reality of service provision for
      (potentially) chronic diseases such as F20-F29 we need to explore further current
      and new data sources, diminish sectoral borders, and implement health care
      responsibility on the level of catchment areas.

PMID- 29029973
TI  - Comparing the management of constipation and distal intestinal obstruction
      syndrome between paediatricians and adult physicians.

PMID- 29029974
TI  - Altered cardiac gene expression of noradrenaline enzymes, transporter and beta
      adrenoceptors in rat model of rheumatoid arthritis.
AB  - Baseline sympathetic activity was found to be elevated in rheumatoid arthritis
      (RA) patients and it is related to increased cardiovascular risk in these
      patients. Although many studies have highlighted the association between RA and
      increased cardiac sympathetic activity, the underlying mechanistic links remain
      unclear. The aim of the present study was to understand how diseases-triggered
      changes in gene expression may result in maladaptive physiological changes. Our
      results suggest that the equilibrium between noradrenaline synthesis, release and
      reuptake was disrupted in the ventricles of arthritic rats. In the acute phase of
      the arthritic process, decreased gene expression of MAO-A might lead to
      accumulation of noradrenaline in myocardial interstitial space, whereas increased
      gene expression of NET protected cardiomyocytes from the deleterious effects of
      enhanced noradrenaline. During the chronic phase, reduced expression of beta1
      adrenoceptor and decreased efficiency of noradrenaline reuptake contribute to
      progressive damage of the myocardium and limits heart efficiency.

PMID- 29029975
TI  - Distressed setting and profound challenges: Pandemic influenza preparedness plans
      in the Eastern Mediterranean Region.
AB  - BACKGROUND: Influenza pandemics are unpredictable and can have severe health and
      economic implications. Preparedness for pandemic influenza as advised by the
      World Health Organization (WHO) is key in minimizing the potential impacts.
      Pandemic Influenza Preparedness (PIP) Framework is a global public-private
      initiative to strengthen the preparedness. A total of 43 countries receive funds
      through Partnership Contribution (PC) component of PIP Framework to enhance
      preparedness; seven of these fall in the WHO's Eastern Mediterranean Region. We
      report findings of a desk review of preparedness plans of six such countries from
      the Region. METHODS: The assessment was done using a standardized checklist
      containing five criteria and 68 indicators. The checklist was developed using the
      latest WHO guidelines, in consultation with influenza experts from the Region.
      The criteria included preparation, surveillance, prevention and containment, case
      investigation and treatment, and risk communication. Two evaluators independently
      examined and scored the plans. RESULTS: Pandemic preparedness plan of only one
      country scored above 70% on aggregate and above 50% on all individual criteria.
      Plans from rest of the countries scored below satisfactory on aggregate, as well
      as on individual preparedness criteria. Among the individual criteria, prevention
      and containment scored highest while case investigation and treatment, the lowest
      for majority of the countries. In general, surveillance also scored low while it
      was absent altogether, in one of the plans. CONCLUSIONS: This was a desk review
      of the plans and not the actual assessment of the influenza preparedness.
      Moreover, only plans of countries facilitated through funds provided under the PC
      implementation plan were included. The preparedness scores of majority of
      reviewed plans were not satisfactory. This warrants a larger study of a
      representative sample from the Region and also calls for immediate policy action
      to improve the pandemic influenza preparedness plans and thereby enhance pandemic
      preparedness in the Region.

PMID- 29029976
TI  - Extraction and RT-qPCR detection of enteroviruses from solid environmental
      matrixes: Method decision tree for different sample types and viral
      concentrations.
AB  - Quantitative RT-PCR methods (RT-qPCR) are becoming increasingly desirable for the
      detection of enteric viruses in solid environmental matrixes such as sediments,
      soils and sewage sludge. However, effective methodologies that allow the
      extraction of high quality RNA ready for molecular quantification continue to be
      evaluated. In the present study, four different methods for enterovirus
      extraction from solid environmental matrixes were compared in terms of viral
      recovery and inhibitor removal. Three indirect methods based on glycine elution
      and concentration by ultracentrifugation were tested. The main differences
      between indirect methods were the sample to glycine buffer ratio, and the
      ultracentrifugation protocol applied. One commercial direct method was also
      tested. The indirect methods produced better results than the direct method. The
      ultracentrifugation led to viral losses in samples with high titers; however, as
      the virus concentration reduced, the ultracentrifugation became increasingly
      important for viral recovery. Two commercial RNA extraction kits were also
      evaluated and it was selected the most effective in removing RT-qPCR inhibitors.
      The results obtained allowed the development of a method decision tree with three
      versions that are suitable for different samples and viral concentrations.

PMID- 29029977
TI  - Spontaneous luminescence color change in the firefly luciferase assay system.
AB  - The temporal effects of luciferase reaction luminescence have only been discussed
      in the context of light intensity (flash vs. glow). However, alterations in the
      color of the light emitted over the course of the luciferase reaction have not
      been reported. Here, we show a temporal change in the light color emitted during
      the reaction catalyzed by unmodified firefly luciferase when concentrations of
      one of the substrates, adenosine triphosphate (ATP), are gradually increased. The
      temporal color change from green to red occurs within the first few minutes of
      the luciferase reaction when an ATP-containing solution is either added or
      synthesized in situ with the aid of an autocatalytic reaction occurring
      simultaneously. This color change is not accompanied by pH changes. An analysis
      of the red and green channels demonstrates dissimilar kinetics, suggesting the co
      existence of two or more temporally shifted luminescence pathways. The
      implications of these findings might improve dual-color biosensing/imaging
      protocols and influence the engineering of biophotonic systems.

PMID- 29029978
TI  - A multiplex RNA quantification method to determine the absolute amounts of mRNA
      without reverse transcription.
AB  - We have developed a highly sensitive microarray-based method that determines the
      absolute amounts of mRNA in a total RNA sample in a multiplex manner without
      reverse transcription. This direct mRNA measurement promotes high-throughput
      testing and reduces bias in transcriptome analyses. Furthermore, quantification
      of the absolute amount of mRNA allows transcriptome analysis without common
      controls or additional, complicated normalization. The method, called Photo-DEAN,
      was validated using chemically synthesized RNAs of known quantities and mouse
      liver total RNA samples. We found that the absolute amounts of mRNA were
      successfully measured without the cDNA synthesis step, with a sensitivity of 15
      zmol achieved in 7 h.

PMID- 29029979
TI  - Immunoaffinity capture coupled with capillary electrophoresis - mass spectrometry
      to study therapeutic protein stability in vivo.
AB  - Protein engineering is at an all-time high in biopharmaceutics. As a result,
      absorption, distribution, metabolism and excretion (ADME) of proteins has become
      more important to understand in the context of engineering strategies to optimize
      therapeutic properties of potential lead constructs. Immunoaffinity capture
      coupled with a newly developed capillary electrophoresis - mass spectrometry (CE
      MS) system was used to characterize intact protein mass analysis of a wild type
      Fc-FGF21 construct and a sequence re-engineered Fc-FGF21 construct from an in
      vivo study. A number of truncated forms were observed and the time courses of the
      various proteolytic products were identified and compared between the two
      constructs. The abundances of the intact and truncated forms were used to provide
      the basis to semi-quantify ADME properties of the two protein forms. The use of
      this immunoaffinity capture followed by CE-MS based intact mass analysis workflow
      provided a qualitative and quantitative analysis of the pharmacokinetic profiles
      of the two proteins. The platform presented here holds great potential in
      characterization of the ADME properties of proteins.

PMID- 29029980
TI  - Sol-gel derived flexible silica aerogel as selective adsorbent for water
      decontamination from crude oil.
AB  - Oil spills are the most important threat to the sea ecosystem. The present study
      is an attempt to investigate the effects of sol-gel parameters on seawater
      decontamination from crude oil by use of flexible silica aerogel. To this goal,
      methyltrimethoxysilane (MTMS) based silica aerogels were prepared by two-step
      acid-base catalyzed sol-gel process, involving ambient pressure drying (APD)
      method. To investigate the effects of sol-gel parameters, the aerogels were
      prepared under two different acidic and basic pH values (i.e. 4 and 8) and varied
      ethanol/MTMS molar ratios from 5 to 15. The adsorption capacity of the prepared
      aerogels was evaluated for two heavy and light commercial crude oils under
      multiple adsorption-desorption cycles. To reduce process time, desorption cycles
      were carried out by using roll milling for the first time. At optimum condition,
      silica aerogels are able to uptake heavy and light crude oils with the order of
      16.7 and 13.7, respectively.

PMID- 29029981
TI  - Beach litter dynamics on Mediterranean coasts: Distinguishing sources and
      pathways.
AB  - We assessed amounts, composition and net accumulation rates every ~15days of
      beach macro litter (>=2.5cm) on 4 Mediterranean beaches, on Corfu island, N.
      Ionian Sea, taking into account natural and anthropogenic drivers. Average net
      accumulation rate on all beaches was found 142+/-115N/100m/15d. By applying a
      Generalized Linear Model (GzLM) it was shown that sea transport is the dominant
      pathway affecting the amount and variability in beach litter loadings. Principal
      Component Analysis (PCA) on compositional data and indicator items discerned two
      more pathways of beach litter, i.e. in situ litter from beach goers and wind
      and/or runoff transport of litter from land. By comparing the PCA results to
      those from a simple item to source attribution, it is shown that regardless their
      source litter items arrive at beaches from various pathways. Our data provide
      baseline knowledge for designing monitoring strategies and for setting management
      targets.

PMID- 29029982
TI  - A change in phytoplankton community index with water quality improvement in Tolo
      Harbour, Hong Kong.
AB  - Water quality in Tolo Harbour and Channel (Tolo) has been improved since 1998
      after the diversion of sewage effluent. However, it remains poorly understood how
      nutrient loading reduction has impacted the phytoplankton community. To evaluate
      this, we applied a Phytoplankton Community Index PI(mp) to the 23-year data (1991
      2013) at inner (TM4) and outer (TM8) sites in Tolo, with the former being more
      eutrophic than the latter. The results show that 1) the phytoplankton community
      changed with time after sewage diversion; 2) "diatoms and dinoflagellates" were
      better indicators of nutrient impact than "autotrophic/mixotrophic and
      heterotrophic dinoflagellates"; 3) the rate of recovery differed between the two
      stations, but both reached a similar state at a similar time; 4) seasonality of
      the phytoplankton community showed greater disturbance in spring than in other
      seasons. Our findings indicate that the nutrient reduction in the Tolo resulted
      in a positive change in the phytoplankton community.

PMID- 29029983
TI  - Distribution and key influential factors of dissolved oxygen off the Changjiang
      River Estuary (CRE) and its adjacent waters in China.
AB  - Based on two multidisciplinary investigations conducted in summer and winter
      2015, the distribution of dissolved oxygen (DO) and the associated seasonal
      variations off the Changjiang River Estuary (CRE) were studied. The DO content
      was high in winter, ranging from 6.81-10.29mg/L, and the distribution was mainly
      controlled by temperature and salinity. The DO concentration was 1.92-9.67mg/L in
      summer, and a hypoxic zone (DO<3mg/L) covered 14,800km2, which was mainly
      controlled by stratification and organic matter decomposition. The hypoxic zone
      exhibited a "dual-core" structure and the differences in the biochemical and
      physical processes between the southern and northern regions were compared: the
      northern region exhibited stronger pycnocline intensity; while larger biomass and
      higher TOC as well as TN contents were observed in the southern region. Hypoxia
      in the northern region might be mainly dominated by stratification, while that in
      the southern region was mainly associated with organic matter decomposition.

PMID- 29029984
TI  - Sleep, sleep apnea and atrial fibrillation: Questions and answers.
AB  - Sleep apnea (SA) is a common sleep disorder increasingly recognized as a risk for
      cardiovascular disease. Atrial fibrillation (AF) is the most common cardiac
      arrhythmia and is associated with significant morbidity and mortality. An
      increasing number of investigations in recent years have linked SA to AF. In this
      review, we aim to provide a critical overview of the existing evidence in a
      question and answer format by addressing the following: What is the prevalent
      association between the two conditions (separating nocturnally detected AF
      episodes from AF as a prevalent condition)? Is SA a risk factor for incident AF?
      Is SA a risk factor for recurrence of AF following cardioversion/catheter-based
      ablation? What is the association between SA and AF in patients with heart
      failure? Are there signature electrocardiographic markers of AF found in patients
      with SA? Are there electrophysiology-based studies supporting the link between SA
      and AF? What other sleep characteristics (beyond SA) are found in patients with
      AF? What is the impact of SA treatment on AF? What is the effect of AF treatment
      on sleep? Finally, we address unsolved questions and suggest future directions to
      enhance our understanding of the AF-SA relationship.

PMID- 29029985
TI  - Clinical and pathological outcomes after irreversible electroporation of the
      pancreas using two parallel plate electrodes: a porcine model.
AB  - BACKGROUND: Irreversible electroporation (IRE) by inserting needles around the
      tumor as treatment for locally advanced pancreatic cancer entails several
      disadvantages, such as incomplete ablation due to field inhomogeneity, technical
      difficulties in needle placement and a risk of pancreatic fistula development.
      This experimental study evaluates outcomes of IRE using paddles in a porcine
      model. METHODS: Six healthy pigs underwent laparotomy and were treated with 2
      separate ablations (in head and tail of the pancreas). Follow-up consisted of
      clinical and laboratory parameters and contrast-enhanced computed tomography
      (ceCT) imaging. After 2 weeks, pancreatoduodenectomy was performed for histology
      and the pigs were terminated. RESULTS: All animals survived 14 days. None of the
      animals developed signs of infection or significant abdominal distention. Serum
      amylase and lipase peaked at day 1 postoperatively in all pigs, but normalized
      without signs of pancreatitis. On ceCT-imaging the ablation zone was visible as
      an ill-defined, hypodense lesion. No abscesses, cysts or ascites were seen.
      Histology showed a homogenous fibrotic lesion in all pigs. CONCLUSION: IRE
      ablation of healthy porcine pancreatic tissue using two plate electrodes is
      feasible and safe and creates a homogeneous fibrotic lesion. IRE-paddles should
      be tested on pancreatic adenocarcinoma to determine the effect in cancer tissue.

PMID- 29029986
TI  - Radiofrequency ablation for colorectal cancer liver metastases initially greater
      than 25 mm but downsized by neo-adjuvant chemotherapy is associated with
      increased rate of local tumor progression.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is a valid treatment for liver
      metastases from colorectal cancer (CRLM) smaller than 25 mm and unsuitable for
      surgical resection. Tumor size is predictive for local tumor progression (LTP).
      The aim of this study was to evaluate whether RFA is indicated for lesions >25 mm
      at presentation but <25 mm after chemotherapy. METHOD: Patients who underwent RFA
      for CRLM after chemotherapy (January 2004-December 2012) were reviewed.
      Metastases were classified according to their size. Group 1: <=25 mm before and
      after chemotherapy. Group 2A: >25 mm before but <=25 mm after chemotherapy. Group
      2B: >25 mm before and after chemotherapy. RESULTS: 133 CRLM were ablated in 83
      patients (median follow-up 56 months). At 1-year, the LTP rate was higher in
      group 2A than in group 1 (32% vs. 16%, p <= 0.001). The highest rate of 1-year
      LTP was 64% in group 2B. Time to LTP (TLTP) was shorter in group 2A than in group
      1 (HR: 2.89; 95% CI [1.04-8.01]; p = 0.004). Following multivariate analysis, the
      group type was the only predictive factor for TLTP (p < 0.001). CONCLUSIONS: RFA
      is not the optimal treatment for CRLM > 25 mm at presentation.

PMID- 29029987
TI  - Multiple extensor tendons reconstruction with hamstring tendon grafts and flap
      coverage for severe dorsal hand injuries.
AB  - : Treatment of patients with traumatic loss of skin and multiple extensor tendons
      on the dorsum of the hand is a challenge. The aim of this study was to assess the
      outcome after reconstruction of soft tissues and multiple extensor tendons in
      patients who suffered traumatic loss of skin and multiple extensor tendons. Ten
      patients were enrolled in the study. These patients underwent single-stage
      reconstruction with autogenous hamstring tendon grafts for multiple extensor
      tendon defects and fasciocutaneous flaps for coverage of dorsal hand defects. In
      total, 25 tendons (2 tendons in 5 patients and 3 tendons in 5 patients) were
      reconstructed. The semitendinosus tendon was used in all patients and the
      gracilis tendon was added in five patients for tendon reconstruction. Total
      tendon length requiring reconstruction was between 9cm and 31cm. Free
      anterolateral thigh flaps were used in six patients and reverse pedicled forearm
      flaps were used in four patients. According to Miller's scoring system, 8 fingers
      had excellent results, 12 fingers had good results and 5 fingers had fair results
      at the final follow-up. Hamstring tendons can be used satisfactorily for primary
      reconstruction of multiple digital extensor tendons due to their availability and
      compatibility, with a fasciocutaneous flap. LEVEL OF EVIDENCE: IV.

PMID- 29029988
TI  - Mandibular embryonal rhabdomyosarcoma with cartilaginous metaplasia: report of a
      case and review of literature.
AB  - Rhabdomyosarcoma (RMS) is a malignant tumor of skeletal muscle origin and
      frequently involves the head and neck region. It represents the second most
      common pediatric soft tissue sarcoma and accounts for 3% of all childhood
      cancers. Here, we report a case of embryonal RMS presenting as a right-sided
      facial swelling in a 7-year-old boy. Histologically, the tumor consisted of
      classic embryonal rhabdosarcomatous areas with metaplastic cartilage, in both
      initial biopsy and final resection specimens. Cartilaginous metaplasia arising in
      the background of RMS is a rare finding, thus raising a diagnostic challenge. To
      the best of our knowledge, this represents the first case of RMS with
      cartilaginous metaplasia in the oral cavity.

PMID- 29029989
TI  - The effect of demographic and disease variables on Schneiderian membrane
      thickness and appearance.
AB  - OBJECTIVES: The purpose of this study was to evaluate the prevalence of sinus
      mucosal thickening (MT) and mucosal appearance (MA) in a patient population as
      detected with cone beam computed tomography (CBCT) and to determine the effects
      of various disease and demographic factors on MT and MA. STUDY DESIGN: The
      retrospective study consisted of CBCT images of 1000 maxillary arches in 500
      patients. The arches were divided into 3 groups (atrophic, partially atrophic,
      and nonatrophic) according to the type of the maxillary dental crest. The CBCT
      scans were assessed to detect the prevalence of maxillary sinus MT and MA. chi2
      analysis was used to determine the significance of association of periodontal
      bone loss (PBL), periapical (PA) status, alveolar crest type, age, and gender on
      sinus MT and MA. RESULTS: MT was significantly associated with PBL (P = .004), PA
      status (P = .001), and gender (P < .01). MA was significantly associated with PBL
      (P = .038), PA status (P = .009), and gender (P < .020). There were no
      significant associations between age or crest type and either MT or MA.
      CONCLUSIONS: Periodontal bone loss, PA lesions, and gender may have an
      association with MT of the maxillary sinus.

PMID- 29029990
TI  - 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac
      surgery.

PMID- 29029992
TI  - Rebuttal From Drs Koenig and Lakticova.

PMID- 29029991
TI  - Summary measures of agreement and association between many raters' ordinal
      classifications.
AB  - PURPOSE: Interpretation of screening tests such as mammograms usually require a
      radiologist's subjective visual assessment of images, often resulting in
      substantial discrepancies between radiologists' classifications of subjects' test
      results. In clinical screening studies to assess the strength of agreement
      between experts, multiple raters are often recruited to assess subjects' test
      results using an ordinal classification scale. However, using traditional
      measures of agreement in some studies is challenging because of the presence of
      many raters, the use of an ordinal classification scale, and unbalanced data.
      METHODS: We assess and compare the performances of existing measures of agreement
      and association as well as a newly developed model-based measure of agreement to
      three large-scale clinical screening studies involving many raters' ordinal
      classifications. We also conduct a simulation study to demonstrate the key
      properties of the summary measures. RESULTS: The assessment of agreement and
      association varied according to the choice of summary measure. Some measures were
      influenced by the underlying prevalence of disease and raters' marginal
      distributions and/or were limited in use to balanced data sets where every rater
      classifies every subject. Our simulation study indicated that popular measures of
      agreement and association are prone to underlying disease prevalence.
      CONCLUSIONS: Model-based measures provide a flexible approach for calculating
      agreement and association and are robust to missing and unbalanced data as well
      as the underlying disease prevalence.

PMID- 29029993
TI  - Rebuttal From Drs Cardenas-Garcia and Feller-Kopman.

PMID- 29029994
TI  - POINT: Should All Initial Episodes of Hemoptysis Be Evaluated by Bronchoscopy?
      Yes.

PMID- 29029995
TI  - COUNTERPOINT: Should All Initial Episodes of Hemoptysis Be Evaluated by
      Bronchoscopy? No.

PMID- 29029996
TI  - Erratum to "A dynamic population model for estimating all-cause mortality due to
      lifetime exposure history" [Regul. Toxicol. Pharmacol. 67 (2013) 246-251].

PMID- 29029997
TI  - Correlation of general and oral health-related quality of life in malocclusion
      patients treated with a combined orthodontic and maxillofacial surgical approach.
AB  - PURPOSE: The aim of the study was to collect information about the oral health
      related quality of life (OHRQoL) after combined orthodontic and maxillofacial
      surgical treatment as well as its influence on health-related quality of life
      (HRQoL). MATERIALS AND METHODS: The study includes data from a total of 130
      subjects, 65 of whom (21 male, 44 female, mean age at baseline: 24 years, mean
      age at the time of surgery: 26 years) were compared with control subjects matched
      on the basis of gender and age. The set of questionnaires used consisted of a
      questionnaire advanced by the authors including 35 general and treatment-specific
      questions, and the German version of the validated "Orthognathic Quality of Life
      Questionnaire" (OQLQ) to analyze the specific OHRQoL, and the SF-36 to measure
      HRQoL. RESULTS: The main reason for treatment was most often a combination of
      esthetic and functional complaints. In most cases, the treatment results met the
      expectations of subjects well or very well, particularly in the areas of
      aesthetics and masticatory function. Postoperative numbness or paresthesia were
      present in 59% of patients, especially in the chin and lower lip areas. In all,
      20% of subjects considered the temporary restriction of mouth opening as very
      bothersome. A decrease in HRQoL was noted as compared with the control group in
      the subscales of "role physical" (p < 0.001), "general health" (p = 0.023), and
      "role emotional" (p = 0.007). No differences were found in the "physical
      functioning," "bodily pain," "vitality," "social functioning," and "mental
      health" subscales. The specific OHRQoL resulted in statistically significant
      limitations in the patient group for all areas examined. The "oral function" (p <
      0.001), "dentofacial aesthetics" (p = 0.005), "social aspects" (p = 0.002), and
      "awareness of dentofacial aesthetics" (p = 0.004) values were significantly
      decreased. CONCLUSIONS: Overall, patients expressed a high level of satisfaction
      and approval with regard to the combined orthodontic and maxillofacial surgical
      treatment. However, even after combined orthodontic and maxillofacial surgical
      treatment of malocclusion patients, it is possible to detect smaller limitations
      with regard to the specific OHRQoL, which may have a negative impact on HRQoL.
      Based on the results, a participatory decision-making process focusing on the
      individual therapy-related expectations, desires, and psychological factors of
      the patient concerning the improvements effected by the treatment appears to be
      advisable.

PMID- 29029998
TI  - Introducing the understanding research series.

PMID- 29029999
TI  - DNA-guided assembly of a five-component enzyme cascade for enhanced conversion of
      cellulose to gluconic acid and H2O2.
AB  - Enzymatic fuel cells have received considerable attention because of their
      potential for direct conversion of abundant raw materials such as cellulose to
      electricity. The use of multi-enzyme cascades is particularly attractive as they
      offer the possibility of achieving a series of complex reactions at higher
      efficiencies. Here we reported the use of a DNA-guided approach to assemble a
      five-component enzyme cascade for direct conversion of cellulose to gluconic acid
      and H2O2. Site-specific co-localization of beta-glucosidase and glucose oxidase
      resulted in over 11-fold improvement in H2O2 production from cellobiose,
      highlighting the benefit of substrate channeling. Although a more modest 1.5-fold
      improvement in H2O2 production was observed using a five-enzyme cascade, due to
      H2O2 inhibition on enzyme activity, these results demonstrated the possibility to
      enhance the production of gluconic acid and H2O2 directly from cellulose by DNA
      guided enzyme assembly.

PMID- 29030000
TI  - Occupational asthma from biological pest control in greenhouses.

PMID- 29030001
TI  - The occurrence and characteristics of endoscopically unexpected malignant
      degeneration in large rectal adenomas.
AB  - BACKGROUND AND AIMS: Large non-pedunculated rectal polyps are most commonly
      resected by endoscopic mucosal resection (EMR) or transanal endoscopic
      microsurgery (TEM). Despite pre-procedural diagnostics, unexpected rectal cancer
      is incidentally encountered within the resected specimen. This study aimed to
      compare the diagnostic assessment and procedural characteristics of lesions with
      and without unexpected submucosal invasion. METHODS: A post-hoc analysis of a
      multicenter randomized trial (TREND study) was performed in which patients with a
      non-pedunculated rectal polyp of >=3 cm without endoscopic suspicion of invasive
      growth were randomized between EMR and TEM. RESULTS: Unexpected rectal cancer was
      detected in 13% (27/203) of patients; 15 after EMR and 12 after TEM. Most
      consisted of low-risk T1 cancers (78%, n = 18). There were no differences in the
      diagnostic assessment between lesions with and without unexpected submucosal
      invasion. Diagnostic biopsies revealed similar rates of high-grade dysplasia (28%
      [7/25] vs 18% [26/144]). When compared with EMR of adenomas, EMR procedures of
      unexpected cancers had a lower success rate of submucosal lifting (60% vs 93%, P
      < .001), were more often assessed as endoscopically incomplete (33% vs 10%, P =
      .01), and were more frequently terminated prematurely (60% vs 8%, P = .001).
      CONCLUSIONS: Diagnostic assessment of large non-pedunculated rectal polyps
      revealed similar characteristics between unexpected cancers and adenomas.
      Unexpected cancers during EMR were non-lifting in 40%, endoscopically assessed as
      incomplete in 33%, and terminated prematurely in 60%. In treatment-naive
      patients, these factors should raise suspicion of malignancy and need discussion
      in a multidisciplinary team meeting for decision on further treatment strategies.

PMID- 29030003
TI  - Antegrade ERCP through a spontaneous gastrogastric fistula in a patient with Roux
      en-Y postsurgical anatomy.

PMID- 29030002
TI  - An unusual cause of bowel obstruction diagnosed by EUS.

PMID- 29030004
TI  - Hepatic leukemia-associated macrophages exhibit a pro-inflammatory phenotype in
      Notch1-induced acute T cell leukemia.
AB  - Tumor-associated macrophages (TAMs) are well accepted and the pathological role
      of macrophages in hematopoietic malignancies have been proposed. Hepatomegaly is
      frequently observed in T cell acute lymphoblastic leukemia (T-ALL) patients with
      poor prognosis. However, the role of leukemia-associated macrophages (LAMs) in
      hepatic microenvironment remains unclear. Here, the characteristics of hepatic
      LAMs (H-LAMs) were studied in Notch1 induced T-ALL model. Increase in proportion
      and absolute counts of H-LAMs was detected with infiltration of inflammatory
      cells. Furthermore, H-LAMs exhibited a more M1-like phenotype distinct from that
      of TAMs in hepatocellular carcinoma and LAMs from BM or spleen in leukemia.
      Moreover, H-LAMs expressed increased level of cytokines in charge of recruiting
      inflammatory cells, which contributed to pro-inflammatory hepatic
      microenvironment.

PMID- 29030005
TI  - FOXP3, ICOS and ICOSL gene polymorphisms in systemic sclerosis: FOXP3 rs2294020
      is associated with disease progression in a female Italian population.
AB  - Systemic sclerosis (SSc), an autoimmune disorder, is characterized by
      vasculopathy, inflammation, progressive perivascular and interstitial fibrosis.
      Its pathogenesis is largely unknown, however strong evidences suggest that
      genetic predisposition may contribute to SSc development. Several gene
      polymorphisms involved in regulatory T cell function have been identified in many
      autoimmune diseases, including SSc. Moreover, dysregulation of co-stimulatory
      and/or co-inhibitory signals, including ICOS signalling, can lead to
      autoimmunity. The aim of the present study was to investigate the association of
      the FOXP3 rs2294020, ICOS rs6726035 and ICOSL rs378299 SNPs with both the
      susceptibility and the progression to SSc in an Italian case-series of patients.
      SNP genotyping results were successfully obtained from a total of 350 subjects
      including 166 individuals with SSc and 184 healthy controls. Although analysis
      tests did not show any significant associations between the SNPs under study and
      susceptibility to SSc, the occurrence of FOXP3 rs2294020 in female patients was
      associated with decreased time to progression from early to definite SSc (allelic
      model: HR=1.43; CI=1.03-1.99; p=0.03; dominant model: HR=1.54; CI=1.04-2.28;
      p=0.03). The inclusion of presence of ACA autoantibodies in the model did not
      significantly change the estimates. No conclusions can be drawn for the
      susceptibility to the disease or the time to progression in men due to the low
      statistical power. This study provides evidence of the association of rs2294020
      with SSc evolution in female patients, modulating the time of progression from
      the diagnosis of early SSc to the diagnosis of definite SSc, while no effect on
      SSc susceptibility per se was found. rs2294020 may be considered a disease
      modifying gene-variant rather than a disease-susceptibility SNP in SSc.

PMID- 29030006
TI  - Dexmedetomidine mitigate acute lung injury by inhibiting IL-17-induced
      inflammatory reaction.
AB  - Interleukin-17 (IL-17) is considered to play an important role in the
      pathogenesis of a number of inflammatory conditions. Previous studies
      demonstrated that intranasal injections of IL-17 resulted in pulmonary
      inflammation and lung damage, we therefore hypothesize that dexmedetomidine, a
      potent alpha2 adrenergic receptor agonist that shows anti-inflammation effects in
      several animal models of inflammation, would attenuate IL-17 induced lung injury.
      We examined the lung damage using a histological approach, and assessed the
      number of lung-infiltrating neutrophils in the bronchoalveolar lavage fluid. We
      then compared the production of selected cytokines by measuring their serum
      concentration after various treatments. Finally, we evaluated the expression of
      selected inflammatory genes and activation of NF-kappaB in the lung epithelial
      cells, using real-time PCR and western blot assay, respectively. In every aspect
      of pulmonary inflammation investigated, dexmedetomidine significantly and dose
      dependently attenuated the inflammatory effects of IL-17. Our results not only
      give a comprehensive description of the protective action of dexmedetomidine on
      IL-17 induced acute lung injury, but also provide insights to the underlying
      cellular and molecular mechanisms.

PMID- 29030007
TI  - Pretreatment of a matrix metalloproteases inhibitor and aprotinin attenuated the
      development of acute pancreatitis-induced lung injury in rat model.
AB  - OBJECTIVE: Acute lung injury (ALI) is one of the most common extra-pancreatic
      complications of acute pancreatitis. In this study, we examined the protective
      effect of protease inhibitor aprotinin and a matrix metalloproteinase inhibitor
      (MMPi) on pulmonary inflammation in rats with severe pancreatitis-associated ALI.
      METHOD: A rat model of acute pancreatitis (AP) was established by injecting
      sodium glycodeoxycholate (GDOC) into the pancreatic duct. Pharmacological
      interventions included pretreatment with a protease inhibitor aprotinin (10mg/kg)
      and a matrix metalloproteinase inhibitor (MMPi, 100g/kg). The extent of
      pancreatic and lung injury and systemic inflammation was assessed by examinations
      of blood, bronchoalveolar lavage (BAL), and lung tissue. Pancreatic or lung
      tissue edema was evaluated by tissue water content. Pulmonary arterial pressure
      and alveolar-capillary membrane permeability were evaluated post-injury via a
      catheter inserted into the pulmonary artery in an isolated, perfused lung model.
      RESULTS: Pre-treatment with aprotinin or MMPi significantly decreased amylase and
      lactate dehydrogenase (LDH), and the wet/dry weight ratio of the lung and
      pancreas in AP rats. Compared to the GDOC alone group, administration of
      aprotinin or MMPi prevented pancreatitis-induced IL-6 increases in the lung.
      Similarly, treatment with aprotinin or MMPi significantly decreased the
      accumulation of white blood cells, oxygen radicals, nitrite/nitrates in both
      blood and BAL, and markedly reduced lung permeability. CONCLUSION: Pretreatment
      with either aprotinin or MMPi attenuated the systemic inflammation and reduced
      the severity of lung and pancreas injuries. In short, our study demonstrated that
      inhibition of protease may be therapeutic to pulmonary inflammation in this GDOC
      induced AP model.

PMID- 29030008
TI  - Assessment of leukocyte activity in mice devoid of the glucocorticoid receptor in
      the noradrenergic system (GRDBHCre).
AB  - Disturbances in brain monoamines, overactivity of the hypothalamo-pituitary
      adrenal (HPA) axis and pro-inflammatory tendency in the immune system are the key
      features of depressive disorders. Recently, several murine lines with mutations
      in glucocorticoid receptors (GRs) have been generated and these animals may be
      utilized for study depressive-like disorders. In the present study, we have
      investigated whether selective ablation of GRs in noradrenergic neurons affects
      functional properties of leukocytes and redirects them towards pro-inflammatory
      activity. Transgenic mice selectively devoid of GRs on noradrenergic cells were
      constructed using the Cre/loxP approach. Peritoneal leukocytes were collected
      from mutant and wild type (WT) animals of both sexes and were cultured in vitro
      for 24h both in basal conditions and after application of selected pro- or anti
      inflammatory stimuli. Metabolic activity and adherence were measured in basal
      conditions. Nitric oxide (NO) synthesis and arginase (ARG) activity were assessed
      as the markers of functional status of the cells. Because adult mutant mice lack
      adrenal medulla and thereby peripheral adrenaline, we modulated pro- and anti
      inflammatory culture conditions by addition of noradrenaline (10-6M). Finally,
      effects of in vivo pro-inflammatory challenge (with intraperitoneal
      administration of lipopolysaccharide) on properties of leukocytes were assessed
      24h (in both sexes) and 48h later (in males only). The experiments indicated that
      selective ablation of GR in noradrenergic neurons did not affect fundamental
      properties of peritoneal leukocytes and exerted effects only under conditions of
      selected pro- or anti-inflammatory stimuli in vitro. Stronger response to pro
      inflammatory stimulation in terms of NO synthesis and ARG activity may suggest
      pro-inflammatory tendency in mutant mice. In vivo inflammatory challenge failed
      to show any effect of GR ablation on selected parameters of leukocyte activity.
      Both in vitro studies and in vivo challenge revealed mainly sex-related
      differences in leukocyte activity.

PMID- 29030009
TI  - Immunobiological efficacy and immunotoxicity of novel synthetically prepared
      fluoroquinolone ethyl 6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate.
AB  - The present study examined the cytotoxicity, anti-cancer reactivity, and
      immunomodulatory properties of new synthetically prepared fluoroquinolone
      derivative 6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate (6FN) in
      vitro. The cytotoxicity/toxicity studies (concentrations in the range 1-100MUM)
      are focused on the cervical cancer cells HeLa, murine melanoma cancer cells B16,
      non-cancer fibroblast NIH-3T3 cells and reconstructed human epidermis tissues
      EpiDermTM. The significant growth inhibition of cancer cells HeLa and B16 was
      detected. The cytotoxicity was mediated via apoptosis-associated with activation
      of caspase-9 and -3. After 72h of treatment, the two highest 6FN concentrations
      (100 and 50MUM) induced toxic effect on epidermis tissue EpiDermTM, even the
      structural changes in tissue were observed with concentration of 100MUM. The
      effective induction of RAW 264.7 macrophages cell-release of pro- and anti
      inflammatory TH1, TH2 and TH17 cytokines, with anti-cancer and/or anti-infection
      activities, respectively, has been revealed even following low-dose exposition.

PMID- 29030010
TI  - LPS priming in early life decreases antigen uptake of dendritic cells via NO
      production.
AB  - Immunological mechanisms of hygiene hypothesis are expected to develop a novel
      strategy for allergy prevention. Although a large number of studies has
      investigated the relation between allergies and infection, little is known about
      the influence of the exposure to infections on antigen uptake by dendritic cells
      (DCs). In this study, we examined the effect of lipopolysaccharide (LPS) priming
      in early life on the antigen uptake ability of DCs by using an original mouse
      model. LPS priming in juvenile mice decreased the migration of antigen-capturing
      CD11c+ cells in the lymph nodes, but not in aged mice. Besides, the bone marrow
      derived DCs (BMDCs) from juvenile LPS-primed mice had the poor antigen uptake
      ability, and constitutively produced NO through the inducible nitric oxide
      synthase (iNOS). Interestingly, the LPS priming-induced poor antigen uptake of
      BMDCs was mimicked by the NO donor, and recovered by the iNOS inhibitor.
      Additionally, LPS priming in juvenile mice prevented the allergic reactions, but
      not in aged mice. Our results suggested that an exposure to infections in early
      life prevents allergy through the alteration of the BM cells fate that is to
      induce the differentiation of BM cells into inhibitory DCs such as NO-producing
      DCs.

PMID- 29030011
TI  - Influence of Pasteurella multocida Toxin on the differentiation of dendritic
      cells into osteoclasts.
AB  - Dendritic cells (DC) are antigen-presenting cells that connect the innate and
      adaptive immune system to ensure an efficient immune response during the course
      of an infection. Recently, DC came into the spotlight as a potential source of
      osteoclast progenitors, especially under (auto)inflammatory conditions. The
      virulence factor Pasteurella multocida Toxin (PMT) causes atrophic rhinitis in
      pigs, a disease characterised by a severe reduction of nasal bone. Our group and
      others have shown the potential of PMT in mediating differentiation of
      monocytes/macrophages into bone-resorbing osteoclasts. However, whether DC are
      target cells for PMT-induced osteoclast differentiation, is currently unknown.
      Using different murine DC model systems, we investigated the ability of PMT to
      induce osteoclast formation in DC. Similar to our previous observations in
      macrophages, PMT was endocytosed by DC and triggered intracellular deamidation of
      residue Q209 of the Gq alpha subunit. Still, PMT failed to induce prolonged
      secretion of osteoclastogenic cytokines and osteoclast formation; instead PMT
      treated DC secreted interleukin-12 (IL-12), an inhibitor of osteoclastogenesis.
      In this study, we show that in comparison to bone marrow-derived macrophages, PMT
      induces maturation of DC through increased expression of the activation markers
      CD80 and CD86. As maturation of DC prevents their transdifferentiation into
      osteoclasts, we hypothesize that PMT, a potent osteoclastogenic toxin, fails to
      trigger osteoclastogenesis in DC due to its effect on DC maturation and IL-12
      production.

PMID- 29030013
TI  - Outcomes of patients at estimated low surgical risk undergoing transcatheter
      aortic valve implantation with balloon-expandable prostheses.
AB  - INTRODUCTION AND OBJECTIVES: Transcatheter aortic-valve implantation (TAVI) is an
      accepted treatment for patients with severe aortic stenosis and high surgical
      risk. However, there is lack in data about TAVI in low-risk patients that are
      already being treated with this therapy in some clinical contexts. METHODS: A
      retrospective analysis of patients treated with transfemoral TAVI using Edwards
      Sapien prosthesis in one center was performed, classifying the patients into
      three groups according to the surgical risk (high/intermediate/low risk for STS
      score>8/4-8/<4). Clinical characteristics, procedure and follow-up outcomes were
      collected, comparing the results between low and high surgical risk groups.
      RESULTS: 89 TAVIs using Edwards balloon expandable prosthesis were performed (9
      Sapien XT and 80 Sapien 3 valves were implanted). 40 patients (45%) presented a
      STS score<4, while 33 (37%) had a STS>8. Low-risk patients were significantly
      younger and had lower rates of coronary artery disease, peripheral vascular
      disease, pulmonary lung disease and atrial fibrillation. There were no
      significant differences in most of the technical variables of the procedure,
      apart from vascular complications and complete left bundle branch block after
      valve implant, which were higher in the group with STS>8. Patients of low risk
      presented shorter hospital stay (2,91+/-1,6, vs 4,8+/-3,9 days), with lower rates
      of mortality at mid- and long follow-up (death from any cause 15,2% vs 0%, p
      0,04). CONCLUSIONS: TAVI in low-risk patients is safe and associated with better
      outcome at mid and long-term follow-up compared to high-risk patients.

PMID- 29030012
TI  - MafB enhances efferocytosis in RAW264.7 macrophages by regulating Axl expression.
AB  - The transcription factor MafB is involved in cellular differentiation and
      phagocytosis in macrophages. Macrophages phagocytose apoptotic cells in vivo;
      this process, which is known as efferocytosis, requires Axl receptor tyrosine
      kinase (Axl) activity. However, the association between MafB and efferocytosis,
      as well as that between MafB and Axl, in macrophages is unknown. We hypothesized
      that MafB modulates macrophage efferocytosis by regulating Axl expression.
      Fluorescent-labeled apoptotic thymocytes were added to RAW264.7-MafB-shRNA and
      control cells, and the proportion of phagocytosis-positivey fluorescence
      microscopy and flow cytometry. In addition, Axl mRNA and protein were quantified
      by real-time PCR and western blotting in each group. RAW264.7-MafB-shRNA cells
      were transfected with a plasmid expressing green fluorescent protein (GFP)-tagged
      Axl or a control empty plasmid expressing only GFP. The capacity for phagocytosis
      of apoptotic cells was assessed in GFP-positive cells gated based on fluorescence
      intensity. In RAW264.7-MafB-shRNA cells, capacity for phagocytosis of apoptotic
      thymocytes was significantly reduced compared with that of control cells, as
      determined by fluorescence microscope and flow cytometry. Axl mRNA and protein
      expression was significantly reduced in RAW264.7-MafB-shRNA cells relative to
      control cells. Furthermore, the capacity of RAW264.7-MafB-shRNA cells,
      transfected with an Axl-expressing plasmid, for phagocytosis of apoptotic
      thymocytes was significantly greater than that of cells transfected with the
      control plasmid. Collectively, the present findings indicate that MafB enhances
      efferocytosis by regulating Axl expression in RAW264.7 macrophages.

PMID- 29030014
TI  - Nurses' intention to resign and avoidance of emergency department violence: A
      moderated mediation model.
AB  - BACKGROUND: Studies that examined the negative impact of violence in emergency
      departments on nurses' leave and avoidance behavior are well-documented. However,
      few studies provided an integrated model of how and when violence influences
      their leave and avoidance behavior. PURPOSE: The study adopted Affective Events
      Theory to propose and examine a model of violent events, negative emotions, and
      (leave and avoidance) behaviors on nurses in emergency departments and further
      analyzed whether the model is salient to nurses' occupational burnout, nursing
      experience, and nursing rank. METHOD: The sample included 123 emergency
      department nurses at a teaching hospital in northern, Taiwan. RESULTS: All
      participants had experienced violent incidents within the preceding 6 months.
      Moderated mediation analysis suggested that nurses experienced one of two
      emotional processes following violent incidents: "violence-negative feelings
      toward work-intention to resign" or "violence-negative emotion and physical
      symptoms-avoidance tendencies." Moreover, nurses with high burnout levels
      expressed weaker intention to resign after violent incidents, while nurses with
      more experience and higher rank were less likely to avoid violence after violent
      incidents. CONCLUSION: Emergency nurses do not simply elect to escape but may
      engage in avoidance behavior. This study revealed that how violent incidents
      affect nurses' resignation or avoidance behaviors depends on how they feel.
      Occupational burnout and nurses' attributes affected their behavior.

PMID- 29030015
TI  - Progressive white-matter demyelination in delayed CO poisoning encephalopathy.

PMID- 29030016
TI  - Does a two-year period of orthokeratology lead to changes in the endothelial
      morphology of children?
AB  - PURPOSE: To compare changes in endothelial morphology in the central and superior
      cornea in subjects wearing single-vision spectacles and orthokeratology lenses
      over two years. METHODS: Endothelial images of the two locations of 99 subjects
      (6-12 years) from completed myopia control studies were analysed. Endothelial
      cell density (ECD), coefficient of variation in cell size (CV), and hexagonality
      (HEX) before and two years after treatment were compared between the two groups
      of subjects. RESULTS: Baseline ECD and CV in the central cornea were slightly
      lower than those in the superior cornea, but no significant difference in HEX was
      found in the two corneal locations. After two years, reduction in ECD and
      increase in CV were only significant in the central cornea, but not in the
      superior cornea. Reduction in HEX was significant in both corneal locations.
      Subjects receiving orthokeratology had smaller reduction in ECD in the central
      cornea compared to the controls (orthokeratology: 56+/-94 cells/mm2; control:
      98+/-91 cells/mm2, p=0.024), otherwise, there were no significant differences in
      the changes in endothelial morphology in the two corneal locations between the
      two groups of subjects. CONCLUSIONS: The current study confirmed that there were
      differences in endothelial morphology of central and superior cornea of Chinese
      children aged 6-12 years. The morphological response to normal ageing differed
      between the two corneal locations as reduction in cell density and polymegathism
      were found only in the central cornea whilst pleomorphism was found in both
      locations. Orthokeratology lens wear had minimal effect on the developmental
      changes in endothelial morphology.

PMID- 29030017
TI  - The effect of ageing on the ocular surface parameters.

PMID- 29030018
TI  - Reply to the Letter to the editor.

PMID- 29030019
TI  - In situ different antioxidative systems contribute to the site-specific
      methylmercury neurotoxicity in mice.
AB  - Methylmercury (MeHg), an environmental toxicant, induces site-specific
      neurotoxicity in adult human and animal models. In this study, we demonstrated
      that MeHg-induced neuropathological changes of the brain in mice were remarkable
      in the cerebrocortical neurons of deeper layers (dl-CCNs), but not in the CCNs of
      shallow layers (sl-CCNs) and the hippocampal neurons of cornu ammonis 1 (CA1
      HNs). Total mercury concentration was not corresponded to the pathological
      changes. Here, we investigated the cause of such site-specific MeHg neurotoxicity
      with a focus on in situ antioxidative systems due to its critical role in MeHg
      intoxication. We performed in situ analyses of antioxidative enzymes expression
      using RT-qPCR analyses from laser microdissected sl-CCNs, dl-CCNs, and CA1-HNs
      samples, and immunohistochemistry. The results of antioxidative enzymes
      expression analyses demonstrated the lowest basal expression levels of mRNA and
      proteins, especially manganese superoxide dismutase (Mn-SOD) and glutathione
      peroxidase 1 (GPx1) in dl-CCNs. In addition, the Mn-SOD expression showed a
      lowest response to MeHg in dl-CCNs. We also performed enzymatic activity analyses
      for antioxidative enzymes using separated cerebral cortex and hippocampus. The
      results of enzymatic activity analyses indicate that the expression levels of
      antioxidative enzymes reflect their enzymatic activities. Immunostaining of
      thymidine glycerol, a sensitive oxidative stress marker, showed selectively
      increased expression in dl-CCNs after the exposure to MeHg but not in sl-CCNs and
      CA1-HNs, suggesting the occurrence of MeHg-induced oxidative stress in dl-CCNs.
      The differences in MeHg-induced occurrence of oxidative stress and pathological
      changes in sl-CCNs, dl-CCNs, and CA1-HNs corresponded to the basal level of Mn
      SOD and GPx1 expression and the different protective response of Mn-SOD
      expression to MeHg. These findings suggest that the in situ different
      antioxidative systems play a role in the site-specific neurotoxicity of MeHg.

PMID- 29030020
TI  - The trajectory of positive psychological change in a head and neck cancer
      population.
AB  - A stressful event may be sufficient to challenge a strongly held set of
      assumptions about the world and the self. In some people this may lead to post
      traumatic stress disorder (PTSD) and in others to positive psychological change
      (PPC), whereby a person's reactions to the challenge are beneficial. Little
      research has investigated PPC in people who have had head and neck cancer (HNC).
      The aim of this study was to identify demographic, clinical, and psychological
      factors associated with PPC over time. A cross-sequential study collected data
      over 5 years. Participants were sent the Silver Lining Questionnaire (SLQ; a
      measure of PPC), the University of Washington HNC quality of life measure, and
      the Medical Outcomes Short-Form 12 each year. Additional data were collected from
      clinical records. Analysis using linear mixed-effects modelling revealed that
      participants with lower stage tumours and those who only had a surgical
      intervention reported greater PPC over time. Multivariable modelling adjusting
      for psychosocial variables found that PPC had a quadratic relationship with time
      since diagnosis, increasing initially and levelling off after 18 months. These
      findings build on the minimal PPC research with people following HNC. In
      particular it demonstrates a model of trajectories for the development of PPC
      longitudinally over time.

PMID- 29030021
TI  - Hypoxic volume evaluated by 18F-fluoromisonidazole positron emission tomography
      (FMISO-PET) may be a prognostic factor in patients with oral squamous cell
      carcinoma: preliminary analyses.
AB  - Tumour hypoxia can be detected by 18F-fluoromisonidazole positron emission
      tomography (FMISO-PET). Few studies have assessed the relationships of new PET
      parameters, including hypoxic volume (HV), metabolic tumour volume (MTV), and
      total lesion glycolysis (TLG), with 5-year survival of patients treated
      surgically for oral squamous cell carcinoma (OSCC). This study evaluated the
      relationships between these PET parameters and 5-year survival in OSCC patients.
      Twenty-three patients (age 42-84 years; 15 male, eight female) with OSCC
      underwent FMISO- and 18F-fluoro-2-deoxyglucose (FDG)-PET computed tomography
      before surgery. All of them underwent radical surgery and were followed up for
      more than 5 years. The FDG-PET maximum standardized uptake value (SUVmax), HV,
      MTV, and TLG were measured. The ability of PET parameters to predict disease-free
      survival (DFS) and loco-regional recurrence (LR) was evaluated using receiver
      operating characteristic curve analysis. During the follow-up period, five of the
      23 patients (22%) died and six (26%) experienced LR. Although FDG-PET SUVmax was
      not significantly associated with DFS or LR, HV correlated significantly with
      both DFS and LR. TLG, but not MTV, was significantly associated with DFS; however
      neither MTV nor TLG was related significantly to LR. In conclusion, tumour HV may
      predict outcomes in patients with OSCC.

PMID- 29030023
TI  - On universal coding events in protein biogenesis.
AB  - The complete ribosomal protein synthesis cycle and codon-amino acids associations
      are universally preserved in all life taxa on Earth. This process is accompanied
      by a set of hierarchically organized recognition and controlling events at
      different complexity levels. It starts with amino acid activation by aminoacyl
      tRNA synthetases (aaRS) followed by matching with the acceptor units of their
      cognate tRNAs ("operational RNA code") and ribosomal codon-anticodon pairing of
      messenger RNA ("triplet code"). However, this codon-anticodon matching is
      possible only when protein translation machinery (translation factors, ribosome)
      accepts an esterified amino acid. This capacity ("charge code") correlates mainly
      with the amino acid nature and the identity elements in the tRNA 3D structure. A
      fourth potential "folding code" (also referred as "stereochemical code") between
      the translation dynamics, sequence composition and folding of the resulting
      protein can also be defined in the frame of the 'Anfinsen dogma' followed by post
      translational modifications. All these coding events as well as the basic
      chemistry of life are deemed invariant across biological taxa due to the
      horizontal gene transfer (HGT) making the 'universal genetic code' the 'lingua
      franca' of life of earth. When cells (or organelles) are prevented from
      transmitting genetic information (i.e., HGT) the deviations in the above
      mentioned coding events become inevitable. A better understanding of these codes,
      in particular the mechanisms of their conservation in the context of HGT could
      provide a guide for the experimental engineering1 of the ribosomal protein
      biosynthesis machinery. This is highly relevant, among others, in attempts to
      create synthetic life forms in genetic isolation by using tailored "minimal
      genomes" and may explain the necessity for multiple coding evens in nature.

PMID- 29030022
TI  - Impact of support networks for breastfeeding: A multicentre study.
AB  - BACKGROUND: The rates of breastfeeding worldwide are slowly improving since 1996.
      Europe is still trailing behind the global breastfeeding incidence and prevalence
      rates. Thus, breastfeeding promotion, protection, prolongation and support have
      become an important challenge as breastfeeding sharply decreases in the first six
      months of life. OBJECTIVES: The aim of this project is to determine, assess and
      identify the real impact of breastfeeding support networks in Murcia (Spain).
      METHODS: After searching unsuccessfully for a validated questionnaire, a specific
      one was developed and validated for measuring the impact of formal and informal
      support networks through five dimensions: satisfaction, consultation, experience,
      problems and support. The questionnaire was provided to 500 mothers with
      experience in breastfeeding, who brought their children to baby paediatricians
      between 2 June and 27 November 2014. Upon completion of the survey and fieldwork,
      a detailed statistical analysis was conducted. RESULTS: The degree of
      satisfaction perceived by the users of the services of support breastfeeding
      networks is remarkable. In addition, mothers who clarified their doubts and
      discussed their problems with health professionals and/or breastfeeding support
      networks were more likely to breastfeed for a longer duration compared to those
      who did not (p=0.005). Furthermore, mothers who sought support in breastfeeding
      are more likely to breastfeed for more than 6 months (p<0.0005). CONCLUSION:
      Based on this information, we conclude that breastfeeding support networks have a
      positive influence in the duration of a women's decision to breastfeed.

PMID- 29030024
TI  - Neurodevelopmental outcomes at 3 years old for infants with birth weights under
      500 g.
AB  - BACKGROUND: Marked improvements have been achieved in the survival of extremely
      low birth weight infants, but survival rates and prognoses of extremely small
      infants with birth weights <=500 g remain poor. The aim of this study was to
      clarify long-term outcomes for surviving infants with birth weights <=500 g.
      METHODS: The study population comprised fetuses of gestational age >=22 weeks,
      expected live- or stillbirth weight <=500 g, and birth date between 2003 and
      2012. Developmental assessments were performed prospectively at 3 years old.
      RESULTS: Data were obtained for 21 fetuses, including 10 live births and 11
      stillbirths. Of the 10 live births, median gestational age was 25.2 weeks (range,
      22.4-27.1 weeks), median birth weight was 426 g (range, 370-483 g), and two
      neonates died before discharge. One infant with severe asphyxia died within 12 h
      and another infant with Down syndrome died at 34 days. The survival rate was thus
      80%. All surviving infants were small for gestational age. Seven of the 8
      surviving infants (88%) weighed less than 2500 g at a corrected age of 40 weeks.
      Seven infants were available for developmental assessments at 3 years old. One
      infant could not be followed. Two of those seven infants (29%) showed normal
      development, three infants (42%) showed mild neurodevelopmental disability, and
      two infants (29%) showed severe neurodevelopmental disability. One infant had
      periventricular leukomalacia and cerebral palsy. Two of the seven infants (29%)
      had short stature (<3 SD) at 3 years old. CONCLUSION: Although the survival rate
      among live births was good (80%) in this study, neurodevelopmental outcomes
      remained poor in infants with birth weights <=500 g. Further large studies are
      needed to assess long-term outcomes for extremely small infants.

PMID- 29030025
TI  - Emerge of blaNDM-1 and blaOXA-48-like harboring carbapenem-resistant Klebsiella
      pneumoniae isolates from hospitalized patients in southwestern Iran.
AB  - BACKGROUND: One of the most important emerging carbapenem-resistant bacteria is
      Klebsiella pneumoniae (K. pneumoniae). The present study aimed to investigate the
      antibiotic susceptibility pattern of K. pneumoniae isolates and detection of
      carbapenemase producing K. pneumoniae obtained from Iranian hospitalized
      patients. METHODS: This cross-sectional study was performed on 211 K. pneumoniae
      isolates which were recovered from different clinical specimens from 2014 to
      2015. Modified Hodge test (MHT) and double disk synergy test (DDST) were done for
      detection of carbapenemase and metallo-beta-lactamase (MBL) producing K.
      pneumoniae. The presence of antibiotic resistance determinants was investigated
      by polymerase chain reaction (PCR) method. RESULTS: The results of antibiotic
      susceptibility showed that all isolates were resistant to ampicillin, and then
      mostly resistant to piperacillin and ceftazidime with 76.3% and 66.8%,
      respectively. On the other hand, the highest sensitivity was toward polymyxin B,
      followed by carbapenems. Of 29 carbapenem-resistant isolates, all were high-level
      imipenem-resistant isolates (Minimum inhibitory concentration >=4), except 4
      isolates. The results of MHT and DDST showed that 93.1% (27/29) of carbapenem
      resistant isolates were carbapenemase and MBL producing isolates, respectively.
      The presence of blaNDM-1 and blaOXA-48-like genes was detected in 27 (10.9%) and
      2 (0.9%) isolates, respectively. CONCLUSION: This is the first identification of
      blaNDM-1 and blaOXA-48-like in K. pneumoniae in Southwestern Iran and the highest
      reported prevalence of blaNDM in this bacterium from Iran. Since carbapenem
      resistant isolates containing New Delhi metallo-beta-lactamase 1 (NDM-1) were
      almost resistant to all the tested antibiotics, the resistance due to this gene
      may be increased in the near future as a potential health threat.

PMID- 29030026
TI  - Nephroprotective effect of electrolyzed reduced water against cisplatin-induced
      kidney toxicity and oxidative damage in mice.
AB  - BACKGROUND: Cisplatin is a potent chemotherapeutic drug for cancer therapy, but
      it has serious side effects in clinical treatment, particularly nephrotoxicity.
      The purpose of this study was to evaluate the protective effect of electrolyzed
      reduced water (ERW) on renal injury caused by cisplatin. METHODS: Animals were
      divided into four groups as follows: normal control group, cisplatin control
      group, ERW control group and ERW + cisplatin group. Each group comprised 10
      animals, which were orally treated with normal saline or ERW daily companion by
      administration of one dose of cisplatin for 28 days. Animals in the cisplatin
      group received an intraperitoneal single-dose injection of cisplatin (20 mg/kg
      body weight) as a single i.p. dose on the 25th day of the experiment. We
      determined the hydration state in urine and the level of serum markers of kidney
      function, the levels of glutathione (GSH) and thiobarbituric acid-reactive
      substances (TBARS) levels and the activities of glutathione peroxidase (GPx),
      glutathione reductase (GR), catalase (CAT) and superoxidase dismutase (SOD) in
      kidney and histopathological changes. RESULTS: After administration of ERW, the
      reduced urinary osmolality was increased and elevated Na+, K+, Mg2+ and Ca2+
      levels in urine were significantly decreased in cisplatin-induced renal injury
      mice. Besides, the results demonstrated that significantly decreased elevated
      serum levels of creatinine and blood urea nitrogen (BUN) and the levels of TBARS
      in the kidneys that were induced by cisplatin. Moreover, ERW treatment was also
      found to markedly increase (p < 0.05) the activities of GPx, GR, CAT and SOD, and
      to increase GSH content in the kidneys. Histopathology showed that ERW protects
      against cisplatin-induced renal injury to both the proximal and distal tubules.
      CONCLUSION: ERW exhibits potent nephroprotective effects on cisplatin-induced
      kidney damage in mice, likely due to both the increase in antioxidant-defense
      system activity and the inhibition of lipid peroxidation.

PMID- 29030027
TI  - Comparison of right ventricular measurements by perioperative transesophageal
      echocardiography as a predictor of hemodynamic instability following cardiac
      surgery.
AB  - BACKGROUND: The relationship between perioperative right ventricular (RV)
      performance and hemodynamic instability after cardiac surgery seemed less
      portrayed. Therefore, we sought to elucidate this relationship and compare the
      accuracy of different RV systolic indices in predicting outcome of cardiac
      surgery. METHODS: This study enrolled consecutive patients referred for cardiac
      surgeries. Exclusion criteria were non-sinus rhythm or contraindications to
      transesophageal echocardiography (TEE). TEE exam and simultaneous pulmonary
      hemodynamics were recorded in two stages: after induction of anesthesia and
      before sternotomy (stage 1), and after sternal closure (stage 2). RV measurements
      performed offline included fractional area change (RVFAC), tricuspid annular
      plane systolic excursion (TAPSE), peak systolic tricuspid annular velocity
      (RVS'), myocardial performance index (RVMPI), and global longitudinal strain
      (RVGLS). The end point was defined as prolonged use (>24 h) of postoperative
      inotropic agent in the intensive care unit (ICU). RESULTS: The study population
      included 68 patients (mean age 61 +/- 11 y; 49 men). Twenty-two of these patients
      (32%) were administered inotropic agents for a prolonged period with a mean
      duration of 63.9 +/- 5.3 h, accompanied with significantly longer ventilator use
      (p = 0.006) and longer ICU stay (p = 0.001) than patients without a prolonged
      inotropic agent use. Multivariable analysis demonstrated that only RVGLS in
      either stage 1 (odds ratio [OR] 1.11, p = 0.048) or stage 2 (OR 1.15, p = 0.018)
      was significantly associated with the outcome, especially a RVGLS > -13.5% in
      stage 2 demonstrating high risk of prolonged inotropic agent use after cardiac
      surgery (OR 7.37, p = 0.016). CONCLUSION: RVGLSs performed using perioperative
      TEE are reliably associated with hemodynamic instability following cardiac
      surgery. This finding adds substantial information to postoperative critical
      care.

PMID- 29030028
TI  - [Alberic Pont, the great war and the "broken faces"].
AB  - The First World War and the number of facial injuries made specialized trauma
      centers necessary. Alberic Pont was trained both in medicine and dentistry. He
      founded in Lyon one of the first French specialized wards, which received more
      than 7000 soldiers overall. Through his charisma, his skills, his creativity and
      his generosity, he must be considered as a symbol among the pioneers of maxillo
      facial surgery, which was then at its early stage. The centenary of World War I
      is the occasion to shed light on this man who dedicated his career to those who
      were renamed "broken faces".

PMID- 29030029
TI  - Improving free-flap survival using intra-operative heparin: Ritualistic practice
      or evidence-base medicine? A systematic review.
AB  - INTRODUCTION: The failure rate of free flaps is approximately 5%, mostly due to
      thrombosis of microvascular anastomosis. A number of pharmacological agents have
      been tested in order to enhance the patency of microvascular anastomosis and so
      to as extend the survival of free flaps. One of them is heparin, a very commonly
      used anticoagulant. However, there exists no consensus on its use in microsurgery
      as concerns time of introduction (pre-, intra- or post-operative), recommended
      dosage, or duration of utilization. The aim of this study was to determine
      whether or not the use of intra-operative heparin, in its systemic or topical
      forms, can bring about improved survival of free flaps, and if and when it should
      be recommended in microsurgery. MATERIAL AND METHODS: A systematic review on the
      PUBMED database enabled us to identify articles evaluating the benefits of intra
      operative heparin with regard to free-flap survival. All in all, fifteen articles
      in animal and human research were selected. RESULTS: As far as animal research is
      concerned, 9 studies out of 11 showed the superiority of topical intra-operative
      heparin compared to saline in improving free-flap survival rates through improved
      patency of the anastomosis. As regards systemic intra-operative heparin, on the
      other hand, only two trials out of four yielded favorable results. In clinical
      research in humans, there has been no prospective randomized trial studying the
      action of topical intra-operative heparin in vessel irrigation of ex-vivo free
      flaps before vascular repermeabilisation. However, the preliminary results of
      four trials seem to provide positive arguments for this practice. CONCLUSION: The
      use of systemic per-operative heparin (intravenous injection) does not improve
      the survival of free flaps in either animal models or humans. In animal models,
      however, the use of topical intra-operative heparin (vessel irrigation) has been
      shown to improve the free-flap survival rate by avoiding thrombosis of
      microvascular anastomosis. Finally, in clinical studies concerning humans, as of
      now no prospective randomized trial has proven that use of topical intra
      operative heparin to ensure vessel irrigation in ex-vivo flaps is likely to
      increase free-flap survival. Studies should be conducted to decide whether or not
      to validate a rather ritualistic practice that consists in irrigating the
      relevant vessels before anastomosis; does it or does it not improve the patency
      rate?

PMID- 29030030
TI  - Oncological safety of nipple-sparing prophylactic mastectomy: A review of the
      literature on 3716 cases.
AB  - INTRODUCTION: The objective of our study was to evaluate the risk of cancer after
      prophylactic nipple-sparing mastectomy (PNSM). MATERIAL AND METHODS: The PubMed
      database was consulted using the following key-words: "nipple-sparing
      mastectomy", "prophylactic", "locoregional recurrence", "oncological risk".
      Articles published between January 1995 and December 2016 were searched. RESULTS:
      Out of the 270 articles found, 19 were included. Overall, 15 studies were
      retrospective, 2 prospective, 2 prospective and retrospective and 3 were
      multicentric. All told, they involved 3890 patients corresponding to 6786
      mastectomies, among which the total number of prophylactic nipple-sparing
      mastectomies was 3716. Average age of the patients was 44.4years and average
      follow-up was 38.4months (8-168months); 29.4% of them had a BRCA 1 or 2 mutation;
      85 and 15% underwent prosthetic and autologous reconstructions, respectively.
      Average cancer rates exterior to and within the nipple areolar complex (NAC) were
      0.2 and 0.004%, respectively. The overall average rate of histological pre
      malignant lesions in the nipple areolar complex was 1.5%. The overall
      complication rate was 20.5%, and necrosis rates of the nipple areolar complex and
      the skin were 8.1 and 7.1%, respectively. CONCLUSION: In prophylactic breast
      surgery, conservation of the nipple areolar complex does not seem to increase the
      risk of cancer development. However, short follow-up time and the different
      methodologies applied in the different studies presently preclude generalization
      of the technique.

PMID- 29030031
TI  - Thermal desorption comprehensive two-dimensional gas chromatography coupled to
      time of flight mass spectrometry for vapour phase mainstream tobacco smoke
      analysis.
AB  - A thermal desorption comprehensive two-dimensional gas chromatography coupled to
      time-of-flight mass spectrometry (TD-GC*GC-TOFMS) method has been developed for
      the analysis of mainstream tobacco smoke (MTS) vapour phase (VP). The selection
      process of the sample introduction approach involved comparing the results
      obtained from three different approaches: a) use of gas sampling bag followed by
      SPME (Tedlar(r)-SPME), b) gas sampling bag followed by TD (Tedlar(r)-TD), and c)
      sampling directly on TD sorbents (Direct-TD). Six different SPME fibers and six
      different TD sorbent beds were evaluated for the extraction capacities in terms
      of total number of peaks and related intensities or peak areas. The best results
      were obtained for the Direct-TD approach using Tenax
      TA/Carbograph1TD/Carboxen1003 sorbent tubes. The optimisation of TD tube
      desorption parameters was carried out using a face-centered central composite
      experimental design and resulted in the use of the Tenax TA/Carbograph
      1TD/Carboxen 1003 sorbent with a 7.5min desorption time, a 60mL/min tube
      desorption flow, and a 250 degrees C tube desorption temperature. The optimised
      method was applied to the separation of MTS-VP constituents, with 665 analytes
      detected. The method precision ranged from 1% to 15% for over 99% of identified
      peak areas and from 0% to 3% and 0% to 1% for both first (1tR) and second (2tR)
      dimension retention times, respectively. The method was applied to the analyses
      of two cigarette types differing in their filter construction. Principal
      component analysis (PCA) allowed a clear differentiation of the studied cigarette
      types (PC1 describing 94% of the explained variance). Supervised Fisher ratio
      analysis permitted the identification of compounds responsible for the chemical
      differences between the two sample types. A set of 91 most relevant compounds was
      selected by applying a Fisher ratio cut-off approach and most of them were
      selectively removed by one of the cigarette filter types.

PMID- 29030032
TI  - A modified approach for isolation of essential oil from fruit of Amorpha
      fruticosa Linn using microwave-assisted hydrodistillation concatenated liquid
      liquid extraction.
AB  - In this work, a modified technique was developed to separate essential oil from
      the fruit of Amorpha fruticosa using microwave-assisted hydrodistillation
      concatenated liquid-liquid extraction (MHD-LLE). The new apparatus consists of
      two series-wound separation columns for separating essential oil, one is the
      conventional oil-water separation column, and the other is the extraction column
      of components from hydrosol using an organic solvent. Therefore, the apparatus
      can simultaneously collect the essential oil separated on the top of hydrosol and
      the components extracted from hydrosol using an organic solvent. Based on the
      yield of essential oil in the first and second separation columns, the effects of
      parameters were investigated by single factor experiments and Box-Behnken design.
      Under the optimum conditions (2mL ethyl ether as the extraction solvent in the
      second separation column, 12mL/g liquid-solid ratio, 4.0min homogenate time,
      35min microwave irradiation time and 540W microwave irradiation power),
      satisfactory yields for the essential oil in the first separation column (10.31+/
      0.33g/kg) and second separation column (0.82+/-0.03g/kg) were obtained. Compared
      with traditional methods, the developed method gave a higher yield of essential
      oil in a shorter time. In addition, GC-MS analysis of the essential oil indicated
      significant differences of the relative contents of individual volatile
      components in the essential oils obtained in the two separation columns.
      Therefore, the MHD-LLE technique developed here is a good alternative for the
      isolation of essential oil from A. fruticosa fruit as well as other herbs.

PMID- 29030033
TI  - A low-cost biosorbent-based coating for the highly sensitive determination of
      organochlorine pesticides by solid-phase microextraction and gas chromatography
      electron capture detection.
AB  - In this study, an environmentally friendly and low-cost biosorbent coating was
      evaluated, for the first time, as the extraction phase for solid-phase
      microextraction (SPME) supported on a nitinol alloy. The characterization of the
      new fiber was performed by Fourier transform infrared spectroscopy (FTIR),
      thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The
      applicability of the biosorbent-based fiber in the determination of delta
      hexachlorocyclohexane, aldrin, heptachlor epoxide, alpha-endosulfan, endrin and
      4,4'-DDD in water samples was verified, with separation/detection by gas
      chromatography coupled to electron capture detection (GC-ECD). The influencing
      parameters (temperature, extraction time and ionic strength) were optimized
      simultaneously using a central composite design. The optimum conditions were:
      extraction time of 80min at 80 degrees C and sodium chloride concentration of 15%
      (w/v). Satisfactory analytical performance was achieved with limits of detection
      (LOD) between 0.19 and 0.71ngL-1 and limits of quantification (LOQ) between 0.65
      and 2.38ngL-1. The relative recoveries for the analytes were determined using
      river and lake water samples spiked at different concentrations and ranged from
      60% for alpha-endosulfan to 113% for delta-hexachlorocyclohexane, with relative
      standard deviations (RSD) lower than 21%. The fiber-to-fiber reproducibility
      (n=3) was also evaluated and the RSD was lower than 14%. The extraction
      efficiency obtained for the proposed biosorbent coating was compared to a
      commercially available DVB/Car/PDMS coating. The proposed fiber provided very
      promising results, including LODs at the level of parts per trillion and highly
      satisfactory thermal and mechanical stability.

PMID- 29030034
TI  - A polyacrylamide-based silica stationary phase for the separation of
      carbohydrates using alcohols as the weak eluent in hydrophilic interaction liquid
      chromatography.
AB  - A hydrophilic interaction liquid chromatography (HILIC) stationary phase was
      prepared by a two-step synthesis method, immobilizing polyacrylamide on silica
      sphere particles. The stationary phase (named PA, 5MUm dia) was evaluated using a
      mixture of carbohydrates in HILIC mode and the column efficiency reached
      121,000Nm-1. The retention behavior of carbohydrates on PA stationary phase was
      investigated with three different organic solvents (acetonitrile, ethanol and
      methanol) employed as the weak eluent. The strongest hydrophilicity of PA
      stationary phase was observed in both acetonitrile and methanol as the weak
      eluent, when compared with another two amide stationary phases. Attributing to
      its high hydrophilicity, three oligosaccharides (xylooligosaccharide,
      fructooligosaccharide and chitooligosaccharides) presented good retention on PA
      stationary phase using alcohols/water as mobile phase. Finally, PA stationary
      phase was successfully applied for the purification of galactooligosaccharides
      and saponins of Paris polyphylla. It is feasible to use safer and cheaper
      alcohols to replace acetonitrile as the weak eluent for green analysis and
      purification of polar compounds on PA stationary phase.

PMID- 29030035
TI  - Quali-quantitative characterization of the volatile constituents in Cordia
      verbenacea D.C. essential oil exploiting advanced chromatographic approaches and
      nuclear magnetic resonance analysis.
AB  - Cordia verbenacea D.C. (Boraginaceae, Varronia curassavica Jacq. synonym) is a
      medicinal plant, native from Brazil, especially the leaves are used in folk
      medicine. The aim of this study was to extend the characterization of the
      volatile fraction of the essential oil obtained from this plant, by using GC-FID,
      GC-MS, and chiral GC. Moreover, to further clarify the composition of the
      volatile fraction, preparative multidimensional-GC (prep-MDGC) was used to
      collect unknown compounds, followed by NMR characterization. Specifically, the
      chemical characterization, both qualitative and quantitative, of the volatile
      fraction of the essential oil obtained from Cordia verbenacea cultivated in the
      Minas Gerais area (central area of Brazil) was investigated for the first time.
      The principal components from a quantitative point of view were alpha-pinene
      (25.32%; 24.48g/100g) and alpha-santalene (17.90%; 17.30g/100g), belonging to the
      terpenes family. Chiral-GC data are reported for the enantiomeric distribution of
      7 different components. Last, to obtain the complete characterization of the
      essential oil constituents, prep-MDGC analysis was used to attain the isolation
      of two compounds, not present in the principal MS databases, which were
      unambiguously identified by NMR investigation as (E)-alpha-santalal and (E)-alpha
      bergamotenal, reported for the first time in Cordia verbenacea essential oil.

PMID- 29030036
TI  - A single-step synthesized supehydrophobic melamine formaldehyde foam for trace
      determination of volatile organic pollutants.
AB  - Superhydrophobic materials have attracted many attentions in recent years while
      their application in sample preparation remained almost intact. In this project,
      a rough surface of melamine formaldehyde foam was silanized by chemical
      deposition of trichloromethylsilane to form a highly porous and superhydrophobic
      material, presumably a suitable medium for extracting non-polar compounds such as
      benzene and its methyl derivatives. The prepared sorbent was packed in a needle
      for the headspace needle-trap microextraction of benzene, toluene, ethylbenzene
      and xylenes (BTEX). Major parameters associated with the extraction/desorption
      processes were considered for optimization. Under the optimized condition, the
      linear dynamic range was from 20 to 1000ngL-1 (R2>0.98). For evaluating the
      method precision, inter-day, intra-day and needle-to-needle relative standard
      deviations (RSD%) were calculated (<13%) for water samples spiked at 500ngL-1 of
      BTEX. The LOD values were in the range of 5-10ngL-1 using gas chromatography
      flame ionization detector (GC-FID). Finally, hookah water was considered as
      suspicious real sample, assumed to contain volatile organic pollutants. Among
      these pollutants, toluene was identified, at the concentration level of 439ngL-1,
      in one of the hookah samples while benzene was detectable at much lower level.
      Also, some other organic pollutants were identified in the smoke and hookah water
      using GC-mass spectrometry (GC-MS). In addition, the suspicious BTEX-containing
      samples from petrochemical waste water of Asalooye (Persian Gulf) were analyzed.

PMID- 29030037
TI  - Solid phase extraction based on porous magnetic graphene oxide/beta-cyclodextrine
      composite coupled with high performance liquid chromatography for determination
      of antiepileptic drugs in plasma samples.
AB  - In this study, a novel solid phase extraction based on porous magnetic graphene
      oxide-cyclodextrin polymers (MGO-CD) was developed with aromatic linker and used
      for the simultaneous extraction and preconcentration of trace antiepileptic drugs
      in plasma. The characteristics of MGO-CD were assessed by Fourier transform
      infrared spectroscopy (FT-IR), Brunauer-Emmett-Teller surface areas (BET),
      Transmission Electron Microscope (TEM), Scanning Electron Microscope (SEM), X-ray
      diffraction (XRD) and vibrating sample magnetometer (VSM). Magnetic cyclodextrin
      polymeric material exhibited a high specific surface area (187m2g-1), large pore
      volume (0.12cm3g-1), good saturated magnetization (37.68emug-1), and excellent
      dispersibility in aqueous solution. Various parameters influencing the extraction
      recovery of drugs were studied. The method exhibited good linearity in the range
      of 1-50MUgmL-1, and the limit of quantitation of carbamazepine, phenytoin,
      diazepam was 11.89, 47.10 and 16.17ngmL-1, respectively. The recoveries of three
      antiepileptic drugs range from 78.49 to 100.93% with relative standard deviations
      less than 5.5%. These analytical results demonstrated that the proposed approach
      based on MGO-CD was applicable for analysis of antiepileptic drugs in plasma
      samples.

PMID- 29030038
TI  - A system map for the ionic liquid stationary phase 1,12
      di(tripropylphosphonium)dodecane bis(trifluoromethylsulfonyl)imide for gas
      chromatography.
AB  - The solvation parameter model is used to prepare a system map for the retention
      of volatile organic compounds on the ionic liquid stationary phase 1,12
      di(tripropylphosphonium)dodecane bis(trifluoromethylsulfonyl)imide (SLB-IL60) by
      gas chromatography over the temperature range 80-280 degrees C. Retention is
      governed by dispersion, dipole-type and hydrogen-bonding interactions with a
      different temperature dependence. The hydrogen-bond acidity of the SLB-IL60
      column is unexpected since the stationary phase contains no hydrogen-bond acid
      groups and is not obviously connected to contributions from the deactivated
      column wall. The polarity number is shown to be a poor indicator of column
      retention properties. Principal component analysis with the system constants of
      the solvation parameter model as variables indicates that the properties of SLB
      IL60 are not duplicated by any of the common poly(siloxane) and poly(ethylene
      glycol) stationary phase chemistries in common use for column preparation. The
      SLB-IL60 column has similar selectivity to a
      poly(cyanopropylphenyldimethylsiloxane) stationary phase containing 50%
      cyanopropylphenyl siloxane monomer but the two columns are not selectivity
      equivalent. Poly(ethylene glycol) stationary phases indicated as most similar to
      SLB-IL60 based on their polarity numbers are shown to have quite different
      selectivity.

PMID- 29030039
TI  - Effect of acidic and enzymatic pretreatment on the analysis of mountain tea
      (Sideritis spp.) volatiles via distillation and ultrasound-assisted extraction.
AB  - A number of beneficial medicinal properties are attributed to the extract and
      essential oil of the aerial parts of Sideritis species (Lamiaceae).
      Hydrodistillation of the aerial parts of wild Sideritis clandestina ssp.
      peloponnesiaca (an endemic taxon in northern Peloponnesus, Greece) gave a low
      essential oil yield (<0.12%); about 65 components, mainly alpha-pinene, beta
      caryophyllene, beta-pinene, globulol, caryophyllene oxide, were identified via GC
      MS. Internal and external standards were used for quantification. For
      miniaturization of the procedure, we studied side-by-side maceration (MAC) and
      ultrasound-assisted extraction (UAE) methods, as well as the effect of
      preincubation in acidic medium (pH 4.8) for 75min at 37 degrees C with or without
      a mixture of cellulase, hemicellulase and pectinase. Maceration and UAE provide
      consistent chemoprofiling of the main volatile compounds (about 20); UAE has
      lower demands on time, solvent, plant material (3g) and results in higher yields.
      Pretreatment with enzymes can increase the respective yields of hydrodistillation
      and UAE, but this effect is definitely attributed to the concurrent acidic
      pretreatment. In conclusion, incubation of plant material prior to
      hydrodistillation or UAE in citrate buffer, pH 4.8, significantly enhances the
      overall yield and number of components obtained and is recommended for the
      analysis of Sideritis volatiles. The acidic pre-treatment method was also
      successfully applied to analysis of cultivated Sideritis raeseri Boiss. & Heldr.
      in Boiss. ssp. raeseri; alpha-pinene, alpha- and gamma-terpinene and beta-thujene
      were predominant albeit in different percentages in flowers and leaves.

PMID- 29030040
TI  - Sedimentation assisted preparation of ground particles of silica monolith and
      their C18 modification resulting in a chromatographic phase of improved
      separation efficiency.
AB  - The sedimentation procedure has been adopted in production of ground silica
      monolith particles to improve chromatographic separation efficiency of the
      resultant phase. First, silica monolith particles have been successfully prepared
      in a large scale by a sol-gel process followed by grinding. The particles after
      calcination were separated by sedimentation into three zones using an Imhoff
      sedimentation cone. The particles of the bottom zone were derivatized with a C18
      ligand and end-capped. The sedimentation process was found to not only eliminate
      troublesome minute particles but also narrow down the particle size distribution.
      The resultant phase was packed in glass lined stainless steel micro-columns. The
      average number of theoretical plates (N) of the columns for a test mixture was
      47,000 and 29,300 for the 300 and 150mm columns (1mm internal diameter),
      corresponding to 157,000/m and 195,000/m, respectively.

PMID- 29030041
TI  - The application of chiral ultra-high-performance liquid chromatography tandem
      mass spectrometry to the separation of the zoxamide enantiomers and the study of
      enantioselective degradation process in agricultural plants.
AB  - In this study, an effective and sensitive chiral analytical method was developed
      to detect zoxamide enantiomers in vegetables, fruits and environmental matrices
      using ultra-high-performance liquid chromatography-tandem mass spectrometry.
      Optimal separation conditions were achieved with Lux Amylose-2 chiral column
      using acetonitrile/water (70:30v/v) as mobile phase with a flow rate and column
      temperature of 0.5mL/min and 25 degrees C. The absolute configuration, optical
      rotation and elution order were confirmed for the first time. The average
      recoveries in all matrices at four spiking levels (0.5, 5, 50, 250MUg/kg) ranged
      from 89.7 to 117.4%, with relative standard deviations being less than 10.9% for
      two enantiomers. The enantioselective dissipation of zoxamide in tomato showed
      that (-)-R-zoxamide was preferentially degraded leading to an enrichment of (+)-S
      isomer, with half-lives of 3.80 d and 5.17 d, respectively. Inversely, (+)-S
      zoxamide degraded faster than (-)-R-zoxamide in pepper (1.95day and 2.28day,
      respectively) and grape (2.03day and 2.87day). No significant enantioselectivity
      was observed in cucumber. The results of this study could help facilitate more
      accurate risk assessments of zoxamide in the future.

PMID- 29030042
TI  - Genetic variability and transcontinental sharing of Giardia duodenalis
      infrapopulations determined by glutamate dehydrogenase gene.
AB  - Microevolutionary data of Giardia duodenalis sub-assemblages is a prerequisite
      for determining the invasion zoonotic patterns of the parasite. To infer
      transmission patterns that could not be differentiated by the phenotypic
      features, a population genetic investigation is crucial for the elucidation of
      the genetic structure of G. duodenalis among the continents. Forty G. duodenalis
      positive fecal samples were collected from different foci of Northwest Iran. The
      specimens were subjected to Trichrome staining and sucrose gradient flotation.
      DNA samples were extracted, amplified, and sequenced by targeting glutamate
      dehydrogenase (gdh) gene. The global gdh sequences of sub-assemblages AII and BIV
      retrieved from NCBI GenBank were analyzed to estimate diversity indices,
      neutrality indices, and gene migration tests. Sequencing analyses indicated
      various levels of genetic variability of sub-assemblages AII and BIV among the
      five continents. Sub-assemblage BIV had greater genetic variability (haplotype
      diversity: 0.975; nucleotide diversity: 0.04246) than sub-assemblage AII. The
      statistical Fst value demonstrated that the genetic structure of sub-assemblages
      AII and BIV are moderately differentiated between European-American populations
      (Fst: 0.05352-0.15182), whereas a significant differentiation was not seen among
      other geographical population pairs. We conclude that a high gene flow of G.
      duodenalis sub-assemblages AII and BIV is unequivocally sharing among the
      continents. The current findings strengthen our knowledge to assess the
      evolutionary patterns of G. duodenalis in endemic foci of the world and it will
      become the basis of public health policy to control human giardiasis.

PMID- 29030043
TI  - Quality of anthelminthic medicines available in Jimma Ethiopia.
AB  - Soil-transmitted helminthiasis and schistosomiasis are major public health
      problems in Ethiopia. Mass deworming of at-risk population using a single dose
      administration of 400mg albendazole (ABZ) or 500mg mebendazole (MBZ) for
      treatment of common intestinal worms and 40mg of praziquantel (PZQ) per kg body
      weight for treatment of schistosomiasis is one of the strategies recommended by
      World Health Organization (WHO) in order to control the morbidity of soil
      transmitted helminthiasis and schistosomiasis. Since storage condition, climate,
      way of transportation and distribution route could all affect the quality of
      medicines, regular assessment by surveys is very critical to ensure the
      therapeutic outcome, to minimize risk of toxicity to the patient and resistance
      of parasites. Therefore, this study was conducted to assess the pharmaceutical
      quality of ABZ, MBZ and PZQ tablet brands commonly available in Jimma town (south
      west Ethiopia). Retail pharmacies (n=10) operating in Jimma town were selected
      using simple random sampling method. Samples of anthelminthic medicines available
      in the selected pharmacies were collected. Sample information was recorded and
      encompassed trade name, active ingredient name, manufacturer's name and full
      address, labeled medicine strength, dosage form, number of units per container,
      dosage statement, batch/lot number, manufacturing and expiry dates, storage
      information and presence of leaflets/package insert. Moreover, a first visual
      inspection was performed encompassing uniformity of color, uniformity of size,
      breaks, cracks, splits, embedded surface spots or visual contaminations. Finally,
      physico-chemical quality attributes investigated encompassed mass uniformity,
      quantity of active pharmaceutical ingredient (API), disintegration and
      dissolution, all following Pharmacopoeial test methods The physical
      characteristics of dosage form, packaging and labeling information of all samples
      complied with criteria given in the WHO checklists. The mass uniformity of
      tablets of each brand of ABZ, MBZ and PZQ complied with the pharmacopoeial
      specification limits, i.e no more than 2 individual masses >5% of average tablet
      weight, and none deviate by more than 10%. The quantity of APIs in all
      investigated tablet brands were within the 90-110% label claim (l.c.) limits,
      ranging between 95.05 and 110.09% l.c. Disintegration times were in line with the
      pharmacopoeial specification limit for immediate release (IR) tablets, ranging
      between 0.5 and 13min. However, the dissolution results (mean+/-SD, n=6) of one
      ABZ brand (i.e. Wormin(r), Q=59.21+/-0.99% at 30min) and two PZQ brands (i.e.
      Bermoxel(r), Q=63.43%+/-0.7 and Distocide(r), Q=62.43%+/-1.67, at 75min) showed
      poor dissolution, failing the United States Pharmacopoeia (USP) dissolution
      specification limit.

PMID- 29030044
TI  - Peripheral Blood Leukocyte Expression of lncRNA MIAT and Its Diagnostic and
      Prognostic Value in Ischemic Stroke.
AB  - BACKGROUND: Ischemic stroke (IS) is an extremely heterogeneous disease with
      variable pathogenesis. Due to the lack of early diagnostic markers, the mortality
      rate of IS remains high. Cumulative evidence shows that long noncoding RNAs among
      noncoding RNAs play important roles in cardiovascular diseases. In the present
      study, we focused on the expression pattern of myocardial infarction-associated
      transcript (MIAT) and its clinical significance in IS. METHODS: Blood samples
      were obtained from IS patients (n = 189) and healthy controls (n = 189). The
      National Institutes of Health Stroke Scale (NIHSS) was measured at the time of
      admission. Short-term functional outcome was measured by the modified Rankin
      Scale (mRS) at 3 months after admission. Multivariate analyses were performed
      using logistic regression models. The receiver operating characteristic (ROC)
      curve was used to evaluate the accuracy of MIAT in the diagnosis and prognosis of
      IS. RESULTS: In IS patients, MIAT expression level was significantly upregulated
      and correlated with NIHSS scores (r = .421, P <.001), mRS (r = .339, P <.001),
      high-sensitivity C-reactive protein (r = .309, P <.001), and infarct volume (r =
      .318, P <.001). ROC curves indicated that MIAT could serve as a potential marker
      for discriminating IS patients from the controls with an area under the curve of
      .842 (95% confidence interval, .802-.881). The overall survival analysis showed
      that patients with higher MIAT expression had a relatively poor prognosis.
      Meanwhile, the multivariate analysis revealed that MIAT was an independent
      prognostic marker of functional outcome and death in patients with IS.
      CONCLUSION: Our data suggested that MIAT might be a potential diagnostic and
      prognostic indicator in IS.

PMID- 29030045
TI  - The Potential Role of Thermography in Determining the Efficacy of Stroke
      Rehabilitation.
AB  - INTRODUCTION: Maintaining good physiological circulation in the extremities
      requires an optimally functioning muscle pump. Stroke symptoms indicate a change
      in venous circulation. In this study, changes were measured in joint function and
      microcirculation, and the correlation between them was examined. SETTING:
      Physiotherapy Center, Ss. Cosmas and Damian Rehabilitation Institute, Visegrad,
      Hungary. METHODOLOGY: Sixteen randomly selected poststroke patients with
      hemiparesis affecting mainly the upper extremities began undergoing
      rehabilitation 13 +/- 4 days following stroke. Thermograms were taken with a
      Fluke Ti 20 (Fluke Corporation, WA) pretreatment and post-treatment, and a
      physiotherapy documentation form was completed. Treatment comprised 15
      physiotherapy, massage, and galvanic therapy sessions per patient, with the side
      exhibiting no neurological symptoms as a control. RESULTS: Joint function showed
      significant improvement on the affected side (P < .05). Thermographic
      examinations revealed microcirculatory dysfunction in the affected extremities in
      100% of the cases. Following treatment, temperature increased significantly (P >=
      .5 degrees C) on the affected side. A strong correlation (r) was observed between
      joint function and temperature change (P < .05). CONCLUSION: Thermography is
      shown to be a reliable method for monitoring the effects of stroke rehabilitation
      treatment. Thermographic testing may enable us to predict the course of the
      trauma and the efficacy of treatment even at the acute stage.

PMID- 29030046
TI  - Ideal Cardiovascular Health and Incidence of Carotid Plaque among Middle-Aged and
      Elderly Adults.
AB  - BACKGROUND: The ideal cardiovascular health (CVH) has been reported to be
      associated with reduced risk of ischemic stroke (IS). Atherosclerosis is a
      fundamental precursor in progression to IS. This study aimed to investigate the
      association of CVH score and atherosclerosis defined by carotid plaque in a
      community-based cohort. METHODS: Data came from the Asymptomatic Polyvascular
      Abnormalities Community study. After exclusions for missing data and original
      carotid plaque, 1938 subjects were included. At baseline (2010), the 7 CVH
      factors were quantified on a 14-point scale with 2 points awarded for ideal
      status, 1 point for intermediate, and 0 point for poor. The incidence of carotid
      plaque from 2010 to 2012 was evaluated from bilateral common, internal, and
      external carotid arteries, and carotid bifurcations using high-resolution B-mode
      ultrasounds. Multivariable logistic models were used to assess the association
      between CVH score and carotid plaque incidence. RESULTS: After 2 years' follow
      up, 350 (18.06%) subjects developed carotid plaque. After adjusting for age, sex,
      education, and income, we observed a significant inverse association between the
      CVH score and incident carotid plaque. For every CVH score increase, the risk of
      carotid plaque incidence decreased by 8.10%. Stratified analysis showed the above
      association had no difference between sexes and age. CONCLUSIONS: Chinese
      subjects with a higher CVH score had a lower risk of developing carotid plaque
      after 2 years. The ideal CVH concept should be further promoted for protecting
      the arteries from atherosclerosis.

PMID- 29030047
TI  - Evaluation of the Time-Dependent Changes and the Vulnerability of Carotid Plaques
      Using Contrast-Enhanced Carotid Ultrasonography.
AB  - BACKGROUND: The association of carotid plaque enhancement on contrast-enhanced
      carotid ultrasound (CEUS) and plaque vulnerability evaluated by magnetic
      resonance imaging (MRI) was to be determined. MATERIALS AND METHODS: The 103
      patients underwent CEUS from May 2013 until June 2016. CEUS images of the carotid
      plaque were obtained offline. Plaque images obtained at 1, 3, 5, and 10 minutes
      were compared with the reference image, defined as the image obtained at 0
      minute. Plaque brightness was assessed using the gray-scale median during
      contrast enhancement (GSM-C). Plaque vulnerability was evaluated using T1- and T2
      weighted MRI and Volume ISotropic TSE Acquisition (VISTA), with a VISTA cutoff
      value for the plaque muscle ratio (PMR) of 1.5. Time-dependent changes in the GSM
      C were evaluated, and those between 0 and 1 minute were compared with the PMR
      values determined on MRI. FINDINGS: GSM-C decreased significantly over time, from
      32.0 at 0 minute to 28.0 at 1 minute, 25.0 at 3 minutes, and 19.0 at 10 minutes.
      The greater the increase in the changes in the GSM-C from 0 to 1 minute, the more
      significant the association with a PMR higher than the median on T1 (GSM-C: 0
      minute: 29.0, 1 minute: 24.0, P = .015), a PMR less than or equal to the median
      on T2 (0 min: 35.0, 1 min: 28.0, P = .003), and a PMR more than 1.5 determined on
      VISTA (GSM-C: 0 minute: 29.0, 1 minute: 24.0, P = .005). CONCLUSIONS: Early
      changes in the GSM-C evaluated with CEUS indicate significant plaque
      vulnerability on MRI.

PMID- 29030049
TI  - More evidence is needed to show any role of cytomegalovisrus and varicella zoster
      virus in pathogenesis of multiple sclerosis.

PMID- 29030048
TI  - Increased Prevalence of Cerebrovascular Disease in Hospitalized Patients with
      Marfan Syndrome.
AB  - BACKGROUND AND PURPOSE: Small studies have suggested that Marfan syndrome is
      associated with a number of cerebrovascular complications. We sought to determine
      whether a clinical diagnosis of Marfan syndrome is associated with a higher
      prevalence of cerebrovascular diseases than the general population by performing
      a case-control study of hospitalized patients in the Nationwide Inpatient Sample
      (NIS). METHODS: Using the 2000-2012 NIS, we performed a case-control study
      matching cases of Marfan syndrome to controls without such a diagnosis. The
      prevalence of various cerebrovascular diseases between the 2 groups were
      compared, and multivariate logistic regression was used to adjust for suspected
      comorbidities. RESULTS: Between 2000 and 2012, there were a total of 13,883
      discharges carrying a diagnosis of Marfan syndrome. On univariate analysis,
      patients with Marfan syndrome were more likely to have a primary or secondary
      diagnosis of hemorrhagic stroke (0.5% versus 0.3%, odds ratio [OR] = 1.56, 95%
      confidence interval [CI] = 1.06-2.29, P = 0.02) as well as intracranial
      hemorrhage (subarachnoid hemorrhage [SAH] and hemorrhagic stroke) (0.3% versus
      0.2%, OR = 1.72, 95% CI = 1.05-2.82, P = 0.03). Patients hospitalized with Marfan
      syndrome were significantly more likely to have carotid dissection (0.3% versus
      0.0%, OR = 11.69, 95% CI = 3.60-38.08, P <. 0001) and cerebral aneurysms (0.2%
      versus 0.1%, OR = 3.67, 95% CI = 1.76-7.68, P = 0.0002). On multivariate analysis
      adjusted for age, race, and comorbidities, patients with Marfan syndrome had
      significantly higher odds of ischemic stroke (OR = 1.20, 95% CI = 1.02-1.43, P =
      0.03), hemorrhagic stroke (OR = 1.75, 95% CI = 1.18-2.63, P = 0.005), carotid
      artery dissection (OR = 11.94, 95% CI = 4.23-50.03, P < 0.0001), and cerebral
      aneurysm (OR = 3.95, 95% CI = 1.95-8.90, P <0.0001). CONCLUSIONS: There is a
      modestly increased prevalence of ischemic stroke, hemorrhagic stroke, and
      cerebral aneurysms in hospitalized patients with Marfan syndrome when compared
      with controls.

PMID- 29030050
TI  - Neural Regeneration a Century after Ramon y Cajal's Decree.
AB  - This Guest Editorial introduces this month's special Neural Regeneration and
      Development Theme Issue, a series of reviews intended to highlight the advances
      in modern neuroscience and to depict the chasms in our understanding of the
      brain.

PMID- 29030051
TI  - Determinants of Axon Growth, Plasticity, and Regeneration in the Context of
      Spinal Cord Injury.
AB  - The mechanisms that underlie recovery after injury of the central nervous system
      have rarely been definitively established. Axon regrowth remains the major
      prerequisite for plasticity, regeneration, circuit formation, and eventually
      functional recovery. The attributed functional relevance of axon regrowth,
      however, will depend on several subsequent conditional neurobiological
      modifications, including myelination and synapse formation, but also pruning of
      aberrant connectivity. Despite the ability to revamp axon outgrowth by altering
      an increasing number of extracellular and intracellular targets, disentangling
      which axons are responsible for the recovery of function from those that are
      functionally silent, or even contributing to aberrant functions, represents a
      pertinent void in our understanding, challenging the intuitive translational link
      between anatomical and functional regeneration. Anatomic hallmarks of
      regeneration are not static and are largely activity dependent. Herein, we survey
      mechanisms leading to the formation of dystrophic growth cone at the injured
      axonal tip, the subsequent axonal dieback, and the molecular determinants of axon
      growth, plasticity, and regeneration in the context of spinal cord injury.

PMID- 29030054
TI  - Inhibiting the CD38/cADPR pathway protected rats against sepsis associated brain
      injury.
AB  - BACKGROUND: The CD38/cADPR pathway has been found to play roles in various
      inflammatory conditions. However, whether CD38 plays a protective or detrimental
      effect in the central nervous system (CNS) is controversial. The aim of this
      study was to determine the effect of CD38/cADPR pathway in sepsis associated
      brain injury. MATERIALS AND METHODS: Male Sprague-Dawley rats were undergone
      cecal ligation and puncture (CLP) or sham laparotomies. NAD+, cADPR and CD38 were
      measured in the hippocampus of septic rats at 0, 6, 12, 24, and 48h after CLP
      surgery. Rats were divided into the sham, CLP group, CLP+ CD38 expression
      lentivirus (CLP+ CD38 LV), CLP+ CD38 interference lentivirus (CLP+ CD38 Ri), CLP+
      negative control lentivirus (CLP+NC) and the CLP+8-Br-cADPR groups. The Western
      blots of Bcl-2, Bax and iNOS, TUNEL assays, malondialdehyde (MDA) and superoxide
      dismutase (SOD) assays, transmission electron microscope analysis were performed
      in the hippocampus of rats. RESULTS: NAD+, cADPR and CD38 levels increased
      significantly in the hippocampus of septic rats as early as 12-24h after CLP
      surgery. CD38 knockdown or blocking cADPR with 8-Br-cADPR significantly reduced
      apoptosis, MDA and SOD activity, iNOS expression and ultrastructural morphology
      damages in the hippocampus of septic rats. CONCLUSIONS: In this study, we found
      that the CD38/cADPR pathway was activated in sepsis associated brain injury.
      Blocking this pathway protected the hippocampus from apoptosis, oxidative stress
      and ultrastructural morphology damages in septic rats.

PMID- 29030052
TI  - Primary Cilia in Brain Development and Diseases.
AB  - The primary cilium, a sensory appendage that is present in most mammalian cells,
      plays critical roles in signaling pathways and cell cycle progression. Mutations
      that affect the structure or function of primary cilia result in ciliopathies, a
      group of developmental and degenerative diseases that affect almost all organs
      and tissues. Our understanding of the constituents, development, and function of
      primary cilia has advanced considerably in recent years, revealing pathogenic
      mechanisms that potentially underlie ciliopathies. In the brain, the primary
      cilia are crucial for early patterning, neurogenesis, neuronal maturation and
      survival, and tumorigenesis, mostly through regulating cell cycle progression,
      Hedgehog signaling, and WNT signaling. We review these advances in our knowledge
      of primary cilia, focusing on brain development, and discuss the mechanisms that
      may underlie brain abnormalities in ciliopathies.

PMID- 29030055
TI  - The heart of PD: Lewy body diseases as neurocardiologic disorders.
AB  - This review provides an update about cardiac sympathetic denervation in Lewy body
      diseases. The family of Lewy body diseases includes Parkinson's disease (PD),
      pure autonomic failure (PAF), and dementia with Lewy bodies (DLB). All three
      feature intra-neuronal cytoplasmic deposits of the protein, alpha-synuclein.
      Multiple system atrophy (MSA), the parkinsonian form of which can be difficult to
      distinguish from PD with orthostatic hypotension, involves glial cytoplasmic
      inclusions that contain alpha-synuclein. By now there is compelling neuroimaging,
      neuropathologic, and neurochemical evidence for cardiac sympathetic denervation
      in Lewy body diseases. In addition to denervation, there is decreased storage of
      catecholamines in the residual terminals. The degeneration develops in a
      centripetal, retrograde, "dying back" sequence. Across synucleinopathies the
      putamen and cardiac catecholaminergic lesions seem to occur independently of each
      other, whereas non-motor aspects of PD (e.g., anosmia, dementia, REM behavior
      disorder, OH) are associated with each other and with cardiac sympathetic
      denervation. Cardiac sympathetic denervation can be caused by synucleinopathy in
      inherited PD. According to the catecholaldehyde hypothesis, 3,4
      dihydroxyphenylacetaldehyde (DOPAL), an intermediary metabolite of dopamine,
      causes or contributes to the death of catecholamine neurons, especially by
      interacting with proteins such as alpha-synuclein. DOPAL oxidizes spontaneously
      to DOPAL-quinone, which probably converts alpha-synuclein to its toxic oligomeric
      form. Decreasing DOPAL production and oxidation might slow the neurodegenerative
      process. Tracking cardiac sympathetic innervation over time could be the basis
      for a proof of principle experimental therapeutics trial targeting DOPAL.

PMID- 29030053
TI  - Function and Dysfunction of Adult Hippocampal Neurogenesis in Regeneration and
      Disease.
AB  - The hippocampus is the only known brain region where physiological neurogenesis
      continues into adulthood across mammalian species and in humans. However, disease
      and injury can change the level of adult hippocampal neurogenesis, which plays an
      important role in regulating cognitive and emotional abilities. Alterations in
      hippocampal neurogenesis can mediate treatment of mental illness or affect the
      brain's capacity for repair and regeneration. In the present review, we evaluate
      how adult neurogenesis contributes to the repair and regeneration of hippocampal
      circuitry in the face of diseases and injuries. We also discuss possible future
      directions for harnessing adult neurogenesis for therapeutic use.

PMID- 29030056
TI  - Development of a generic wound care assessment minimum data set.
AB  - BACKGROUND: At present there is no established national minimum data set (MDS)
      for generic wound assessment in England, which has led to a lack of
      standardisation and variable assessment criteria being used across the country.
      This hampers the quality and monitoring of wound healing progress and treatment.
      AIM: To establish a generic wound assessment MDS to underpin clinical practice.
      METHOD: The project comprised 1) a literature review to provide an overview of
      wound assessment best practice and identify potential assessment criteria for
      inclusion in the MDS and 2) a structured consensus study using an adapted
      Research and Development/University of California at Los Angeles Appropriateness
      method. This incorporated experts in the wound care field considering the
      evidence of a literature review and their experience to agree the assessment
      criteria to be included in the MDS. RESULTS: The literature review identified 24
      papers that contained criteria which might be considered as part of generic wound
      assessment. From these papers 68 potential assessment items were identified and
      the expert group agreed that 37 (relating to general health information, baseline
      wound information, wound assessment parameters, wound symptoms and specialists)
      should be included in the MDS. DISCUSSION: Using a structured approach we have
      developed a generic wound assessment MDS to underpin wound assessment
      documentation and practice. It is anticipated that the MDS will facilitate a more
      consistent approach to generic wound assessment practice and support providers
      and commissioners of care to develop and re-focus services that promote
      improvements in wound care.

PMID- 29030057
TI  - Comparative pattern of growth and development of Echinostoma paraensei (Digenea:
      Echinostomatidae) in hamster and Wistar rat using light and confocal laser
      scanning microscopy.
AB  - Echinostoma paraensei (Digenea: Echinostomatidae) lives in the duodenum and bile
      duct of rodents and is reported as a useful model for studies on the biology of
      flatworms. Here, we compared the growth and development of pre and post ovigerous
      worms collected 3, 7, 14 and 21 days post infection from experimentally infected
      hamster (permissive host) and Wistar rat (less permissive hosts). Linear
      measurements and ratios were examined by light (morphology and morphometry) and
      confocal laser scanning microscopy. At day 3, either worm from hamsters or rats
      were small with poorly developed gonads. At seven day, worms increased in size
      and morphometric differences between hosts are statistically significant after
      this time. In addition, adult worms (14 and 21 days of age) harvested from
      hamster showed developed gonads and vitelline glands laterally distributed on the
      body, whereas worms from rat showed atrophied reproductive system characterized
      by underdeveloped vitelline glands and stunted ovary. The worm rate recovery in
      rat decreased from 29.3% (day 7) to 20.6% (day 14) and 8% (day 21), whilst it
      remained around 37% in hamster. In conclusion, this is the first appointment
      demonstrating that low permissiveness influences the reproductive system of
      echinostome since the immature stages of development. The phenotypic analysis
      evidenced that hamster provides a more favorable microenvironment for gonads
      development than rat, confirming golden hamster as a permissive host, whereas
      Wistar rat is less permissive host.

PMID- 29030059
TI  - Blood Transfusion in Elderly Patients with Acute Myocardial Infarction: Data from
      the RICO Survey.
AB  - BACKGROUND: Red blood cell transfusion benefit during acute myocardial infarction
      remains unclear in the elderly. We aimed to assess the transfusion impact on 1
      year mortality in acute myocardial infarction patients aged >=65 years, according
      to their age and hemoglobin nadir. METHODS: We included 3316 consecutive patients
      with acute myocardial infarction aged >=65 years from the "obseRvatoire des
      Infarctus de Cote d'Or" (RICO) survey. They were categorized according to their
      hemoglobin nadir (<=8, >8 to <=10, and >10 g/dL) and age (<80 or >=80 years).
      RESULTS: A total of 1906 patients (57%) were 65-79 years old, and 1410 (43%) were
      aged >=80 years, of whom 103 (5%) and 145 (10%) patients received red blood cell
      transfusion, respectively (P < .001). In Cox regression analysis, transfusion was
      associated with increased 1-year mortality for hemoglobin nadir >10 g/dL but no
      significant effect for hemoglobin nadir between 8 and 10 g/dL. When hemoglobin
      nadir was <=8 g/dL, transfusion did not influence 1-year mortality for younger
      patients (65-79 years). However, for older patients (>=80 years), transfusion was
      associated with lower mortality (hazard ratio 0.43 [95% confidence interval, 0.22
      0.86], P = .016). CONCLUSION: Among older patients with acute myocardial
      infarction, the effect of transfusion was largely dependent on hemoglobin
      threshold and age. Transfusion was associated with increased 1-year mortality
      when hemoglobin nadir was >10 g/dL. However, in patients aged >=80 years with
      hemoglobin nadir <8 g/dL, transfusion was associated with a 50% reduction in 1
      year mortality.

PMID- 29030060
TI  - Bedside Diagnosis of Deep Vein Thrombosis Using a Pocket-Sized Ultrasound Device.

PMID- 29030061
TI  - Disseminated Histoplasmosis: An Unusual Presentation of a Classic Midwest
      Infection.

PMID- 29030062
TI  - Rare Complication of Cough.

PMID- 29030058
TI  - MDM2 Antagonists Counteract Drug-Induced DNA Damage.
AB  - Antagonists of MDM2-p53 interaction are emerging anti-cancer drugs utilized in
      clinical trials for malignancies that rarely mutate p53, including melanoma. We
      discovered that MDM2-p53 antagonists protect DNA from drug-induced damage in
      melanoma cells and patient-derived xenografts. Among the tested DNA damaging
      drugs were various inhibitors of Aurora and Polo-like mitotic kinases, as well as
      traditional chemotherapy. Mitotic kinase inhibition causes mitotic slippage, DNA
      re-replication, and polyploidy. Here we show that re-replication of the polyploid
      genome generates replicative stress which leads to DNA damage. MDM2-p53
      antagonists relieve replicative stress via the p53-dependent activation of p21
      which inhibits DNA replication. Loss of p21 promoted drug-induced DNA damage in
      melanoma cells and enhanced anti-tumor activity of therapy combining MDM2
      antagonist with mitotic kinase inhibitor in mice. In summary, MDM2 antagonists
      may reduce DNA damaging effects of anti-cancer drugs if they are administered
      together, while targeting p21 can improve the efficacy of such combinations.

PMID- 29030063
TI  - Immediate and midterm results of balloon angioplasty for recurrent aortic
      coarctation in children aged<1 year.
AB  - BACKGROUND: Several publications have considered results of percutaneous
      angioplasty for aortic recoarctation, but none focused on procedures performed in
      children aged<1 year. AIMS: To describe the immediate and midterm results of
      balloon angioplasty for recoarctation before the age of 1 year, and to define the
      factors that might influence outcome. METHODS: We retrospectively reviewed data
      from 20 consecutive children undergoing percutaneous dilatation for aortic
      recoarctation before the age of 1 year in the University Hospitals of Tours and
      Nantes. RESULTS: In all patients except one, dilatation improved the median
      recoarctation diameter Z-score from -5.5 (range -10.6 to -2.5) to -2.8 (range 
      4.3 to 0.7) (P<0.001), and reduced the median peak systolic gradient from 33mmHg
      (range 20 to 60mmHg) to 21mmHg (range 6 to 50mmHg) (P<0.001). There was no
      procedure-induced mortality and no acute intimal flap or long-term aneurysm.
      Three patients experienced a transient femoral artery thrombosis, one of whom had
      a transient ischemic stroke. Eight children (40%) needed reintervention for
      further recoarctation (new surgery [n=4] or new dilatation [n=4]). A smaller
      balloon size was significantly associated with the risk of reintervention:
      balloon to recoarctation diameter ratio 2.0 (range 1.3 to 3.3) vs. 2.7 (range 2.1
      to 4.5) (P=0.05); balloon to descending aorta ratio 0.8 (range 0.7 to 1.2) vs.
      1.0 (range 0.9 to 1.3) (P<0.05). CONCLUSIONS: In this study, percutaneous balloon
      angioplasty for recoarctation in young infants aged<1 year improved aortic
      isthmus diameter with a low incidence of adverse event. However, the rate of
      further intervention is high, and is associated with a smaller balloon size.

PMID- 29030064
TI  - Five-year major clinical outcomes according to severity of coronary artery spasm
      as assessed by intracoronary acetylcholine provocation test.
AB  - BACKGROUND: Long-term clinical outcome data according to severity of coronary
      artery spasm (CAS) as assessed by an intracoronary acetylcholine provocation test
      are limited in series of Asian patients. AIM: To investigate 5-year clinical
      outcomes in patients with CAS according to CAS severity. METHODS: In total, 5873
      consecutive patients with insignificant coronary artery disease (<70% fixed
      stenosis) who underwent an acetylcholine provocation test were enrolled and
      divided into four groups according to CAS severity during the acetylcholine
      provocation test: negative, borderline positive, moderately positive and severely
      positive. CAS severity was assessed by quantitative coronary angiography. We
      investigated 5-year clinical outcomes according to CAS severity. RESULTS: Over a
      follow-up period of up to 5 years, before adjustment, the severely-positive CAS
      group showed a significantly higher incidence of major adverse cardiac events
      (MACE; composite of death, myocardial infarction and de novo revascularization)
      (hazard ratio [HR]: 1.834, 95% confidence interval [CI]: 1.047-3.211; P=0.033),
      total death (HR: 3.124, 95% CI: 1.047-9.322; P=0.041), myocardial infarction (HR:
      3.190, 95% CI: 1.069-9.519; P=0.037) and recurrent angina (HR: 1.762, 95% CI:
      1.363-2.278; P<0.001) compared with the negative group. However, after adjustment
      for baseline confounders, only the incidence of recurrent angina (HR: 1.323, 95%
      CI: 1.014-1.726; P=0.039) was significantly higher in the severely-positive CAS
      group compared with the negative group. CONCLUSIONS: The severity of CAS in the
      positive group was not associated with an increased incidence of MACE after
      adjustment for covariates compared with the negative group, but the severely
      positive CAS group was associated with a higher incidence of recurrent angina
      compared with the negative group.

PMID- 29030065
TI  - Diuretics versus volume expansion in acute submassive pulmonary embolism.
AB  - BACKGROUND: The benefit of volume expansion (VE) in submassive pulmonary embolism
      (PE) with right ventricular (RV) dysfunction is unclear. AIM: To compare the
      effects of diuretic treatment versus VE in patients hospitalized for PE with RV
      dysfunction. METHODS: We prospectively included 46 consecutive patients with
      submassive PE treated on admission with a 40mg bolus of furosemide (D group,
      n=24) or 500mL of saline infusion (VE group, n=22). The primary endpoint was the
      timing of normalization of B-type natriuretic peptide and troponin Ic
      concentrations. The secondary endpoints were variations in RV function variables,
      recorded at baseline, at the 4th hour after treatment initiation (H4) and every
      day until discharge, and a clinical composite endpoint of thrombolysis or death
      at 7 and 30 days. RESULTS: No differences were observed between patients at
      baseline. The primary endpoint occurred earlier in the D group than in the VE
      group (67.5+/-34.8 vs 111.6+/-63.3hours; P=0.006). Furosemide treatment on
      admission was well tolerated, and was not associated with serious adverse events.
      At H4, substantial improvements were observed in the D group versus the VE group
      in terms of heart rate reduction (-8.15+/-21.0 vs -0.71+/-6.30 beats/min; P<0.01)
      and peak tricuspid annular systolic velocity (Doppler tissue imaging) (11.4+/
      2.10 vs 9.90+/-2.80cm/s; P=0.02). There was no significant difference between
      groups in terms of severe outcomes at 7 and 30 days. CONCLUSIONS: In the acute
      management of submassive PE patients, a single furosemide bolus on admission
      seems to produce significant and earlier improvements in RV function markers
      compared with VE, without adverse events.

PMID- 29030066
TI  - Etoposide induced NMI promotes cell apoptosis by activating the ARF-p53 signaling
      pathway in lung carcinoma.
AB  - Lung carcinoma is one of the leading causes of cancer-related death. The N-Myc
      and STATs interactor (NMI) has been reported to take participate in lots of
      physiological processes, but the involvement and functional mechanisms of NMI in
      lung carcinoma are poorly understood. In this study, we found that etoposide
      induces proliferation suppression, cell apoptosis and increases caspase-3
      activity in A549 cells. Furthermore, etoposide treatment up-regulates the
      expression of NMI and ARF, enhances the interaction of NMI and ARF and promotes
      the p53 transcriptional activities. By contrast, when silencing NMI, the
      proliferation suppression and cell apoptosis caused by etoposide were repressed
      and the p53 signaling pathway activation was also suppressed. These
      investigations demonstrated etoposide-induced NMI can suppress tumor
      proliferation and promote cell apoptosis by activating the ARF-p53 signaling
      pathway in lung carcinoma. Our results provide an alternative mechanism for
      etoposide in lung carcinoma and suggest NMI has a critical role in suppressing
      lung carcinoma progression.

PMID- 29030067
TI  - Adipose tissue-derived stem cells in combination with xanthan gum attenuate
      osteoarthritis progression in an experimental rat model.
AB  - The current study explored the efficacy of an intra-articular (IA) injection of
      allogeneic adipose tissue-derived stem cells (ADSCs) combined with xanthan gum
      (XG) in a rat osteoarthritis (OA) model. We confirmed that XG significantly
      inproved proliferation of ADSCs in a dose dependent manner in vitro. The rat OA
      model was induced by an anterior cruciate ligament transection (ACLT), and at 4
      weeks after surgery, rats were divided into four groups: the XG-ADSCs group, the
      ADSCs group, the XG group and the phosphate-buffered saline (PBS) group. A single
      dose of 1 * 106 allogeneic ADSCs suspended in 1% XG, ADSCs suspended in PBS, 1%
      XG alone or PBS alone was injected into the OA joint of rats in the respective
      treatment groups. Rats were sacrificed at 8 weeks after surgery. Treatment
      outcomes were evaluated by weight-bearing control of the hind limbs, gross
      morphological analysis, histological analysis and specific staining of articular
      cartilage, and measurement of inflammatory factors in synovial fluid. For the
      rats in the XG-ADSC-s and ADSCs-treated groups, the weight-bearing percentage of
      the right hind limb was significantly increased compared to that in the PBS group
      and was sustained over 4 weeks. However, the positive effect in the XG-ADSCs
      group was significantly greater than that in the ADSCs group. For the rats in the
      XG group, the efficacy decreased during the third week after surgery. The
      articular cartilage was relatively normal in the XG-ADSCs group, and moderate
      degeneration was observed in the ADSCs and XG groups. ADSCs and XG-ADSC
      treatments significantly decreased the concentrations of IL-1beta, TNF-alpha, MMP
      3 and MMP-13 in synovial fluid; however, the attenuating effect of the XG-ADSCs
      treatment was significantly enhanced compared with that of the ADSCs treatment
      alone. These results indicate that a single IA injection of allogeneic ADSCs
      combined with XG efficiently attenuated OA progression with a therapeutic effect
      that was significantly greater than that of either ADSCs or XG alone. IA
      injection of XG-ADSCs might be an effective treatment for OA in humans.

PMID- 29030068
TI  - Double ovarian stimulation during the follicular and luteal phase in women >=38
      years: a retrospective case-control study.
AB  - Previous studies have shown that double ovarian stimulation could obtain more
      oocytes in women with poor ovarian response. This retrospective case-control
      study aimed to investigate the efficacy of double ovarian stimulation in older
      women. One hundred and sixteen women aged >=38 years who received double ovarian
      stimulation were assigned to the study, with 103 divided into four groups
      according to follicular-phase ovarian stimulation protocols, including
      gonadotrophin-releasing hormone agonist short protocol (n = 27), gonadotrophin
      releasing hormone antagonist protocol (n = 32), mild stimulation protocol (n =
      21) and medrocyprogesterone acetate (MPA) pituitary down-regulation protocol (n =
      23). Numbers of oocytes retrieved and available embryos after double ovarian
      stimulation were more than double those obtained after follicular-phase ovarian
      stimulation alone. In total 81.90% of patients had available embryos, and the
      cancellation rate decreased from 37.07% to 18.10%. Forty-eight cases underwent 50
      cryopreserved embryo transfer cycles, with a 22.00% clinical pregnancy rate. The
      implantation rate (10.53% versus 10.67%) was similar between the embryos derived
      from first and second stimulations. The results suggest that double ovarian
      stimulation could increase the chances of achieving pregnancy by accumulating
      more oocytes/embryos in a short time, which might serve as a useful strategy for
      older women.

PMID- 29030069
TI  - Sex differences and menstrual cycle effects in cognitive and sensory resting
      state networks.
AB  - It has not yet been established if resting state (RS) connectivity reflects
      stable characteristics of the brain, or if it is modulated by the psychological
      and/or physiological state of the participant. Based on research demonstrating
      sex hormonal effects in task-related brain activity, the present study aimed to
      investigate corresponding differences in RS networks. RS functional Magnetic
      Resonance Imaging (RS fMRI) was conducted in women during three different
      menstrual cycle phases, while men underwent three repeated RS fMRI testing
      sessions. Independent component analysis was used to identify the default mode
      network (DMN) and an auditory RS network. For the DMN, RS connectivity was stable
      across testing sessions in men, but varied across the menstrual cycle in women.
      For the auditory network (AN), retest reliable sex difference was found. Although
      RS activity in the DMN has been interpreted as trait characteristic of functional
      brain organization, these findings suggest that RS activity in networks involving
      frontal areas might be less stable than in sensory-based networks and can
      dynamically fluctuate. This also implies that some of the previously reported
      effects of sex hormones on task-related activity might to some extent be mediated
      by cycle-related fluctuations in RS activity, especially when frontal areas are
      involved.

PMID- 29030070
TI  - A latex agglutination assay to quantify the amount of hemagglutinin protein in
      adjuvanted low-dose influenza monovalent vaccines.
AB  - To formulate inactivated influenza vaccines, the concentration of hemagglutinin
      (HA) must be accurately determined. The standard test currently used to measure
      HA in influenza vaccines is the Single Radial Immunodiffusion (SRID) assay. We
      developed a very rapid, simple and sensitive alternative quantitative HA assay,
      namely the Latex Agglutination Assay (LAA). The LAA uses the Spherotest(r)
      technology, which is based on the agglutination of HA-specific immunoglobulin
      coated latex beads. The amount of HA in a sample is calculated from the level of
      bead agglutination by a simple absorbance measurement at 405nm against a standard
      curve generated using a monovalent vaccine standard. In less than 2hours, tens of
      samples could be quantified using the LAA as opposed to 2days for the SRID assay.
      Ten steps are required to complete an SRID assay as compared to 6 steps for the
      LAA, from sample preparation through spectrophotometric analysis. Furthermore,
      the limit of detection of the LAA was found to be approximately 15ng HA/mL,
      similar to an ELISA, with the quantification of less than 1.8MUg HA/mL. The
      quantification limit of the SRID is usually considered to be approximately 5MUg
      HA/mL. The development of the assay and a comparison of the titers obtained by
      SRID and LAA for several monovalent vaccines corresponding to various strains
      were performed. For A/H5N1 and A/H1N1 monovalent vaccines, the LAA was found to
      be linear and accurate as compared to the SRID. The precision of the LAA was
      close to that of the standard test, and good reproducibility from one laboratory
      to another was observed. Moreover, the LAA enabled HA quantification in AlOOH
      adjuvanted and in emulsion-adjuvanted low-dose vaccines as well as unadjuvanted
      vaccines. In conclusion, LAA may be useful to rapidly and accurately measure
      influenza HA protein in monovalent vaccines, especially in those containing less
      than 5MUg/mL of HA in the presence of an adjuvant.

PMID- 29030071
TI  - Single reaction, real time RT-PCR detection of all known avian and human
      metapneumoviruses.
AB  - Current molecular methods for the detection of avian and human metapneumovirus
      (AMPV, HMPV) are specifically targeted towards each virus species or individual
      subgroups of these. Here a broad range SYBR Green I real time RT-PCR was
      developed which amplified a highly conserved fragment of sequence in the N open
      reading frame. This method was sufficiently efficient and specific in detecting
      all MPVs. Its validation according to the NF U47-600 norm for the four AMPV
      subgroups estimated low limits of detection between 1000 and 10copies/MUL,
      similar with detection levels described previously for real time RT-PCRs
      targeting specific subgroups. RNA viruses present a challenge for the design of
      durable molecular diagnostic test due to the rate of change in their genome
      sequences which can vary substantially in different areas and over time. The fact
      that the regions of sequence for primer hybridization in the described method
      have remained sufficiently conserved since the AMPV and HMPV diverged, should
      give the best chance of continued detection of current subgroups and of potential
      unknown or future emerging MPV strains.

PMID- 29030072
TI  - Percutaneous Vesicoscopic Approach for Retrograde Ureteroscopy Following Cohen
      Cross-trigonal Ureteral Reimplantation.
AB  - Obtaining retrograde access into a ureter that has been previously reimplanted in
      a cross-trigonal fashion can be a challenging procedure. We describe a
      percutaneous vesicoscopic approach to obtain access into a reimplanted ureter to
      perform ureteroscopy and laser lithotripsy.

PMID- 29030073
TI  - Comparative Analysis of Surgery, Thermal Ablation, and Active Surveillance for
      Renal Oncocytic Neoplasms.
AB  - OBJECTIVE: To compare oncological and procedural outcomes for renal oncocytic
      tumors treated with surgery, thermal ablation, or active surveillance. METHODS:
      Clinical and pathologic data were collected for consecutive patients with a
      histologic diagnosis of oncocytoma, oncocytic neoplasm, or chromophobe renal cell
      cancer (chRCC) from 2003 to 2016. Independent pathology and radiology reviews
      were performed for this study. RESULTS: Of 171 patients, tumor histology included
      oncocytoma (n = 122), chRCC (n = 47), and oncocytic neoplasm not otherwise
      specified (n = 2). At the initial diagnosis, 67, 14, and 90 patients were treated
      with surgery, thermal ablation, and active surveillance. In 3 of 19 patients
      (16%) who had biopsy and subsequent surgery, diagnosis changed from oncocytoma to
      chRCC. The median follow-up was 39.9 months with no difference among choices of
      treatment modalities (P = .33). Of 90 patients who began active surveillance, 32
      (36%) switched to active treatments (19 underwent thermal ablation and 13
      underwent surgery). The median linear growth rate for patients on active
      surveillance was 1.2 mm/y. No patients who were managed with active surveillance
      developed metastatic renal cell cancer (mRCC). mRCC was identified in 3 patients
      and was the cause of death in 2 patients. Patients who developed metastatic
      disease presented with symptomatic tumors of >4 cm and were treated with
      immediate surgery. For oncocytic masses of <=4 cm (n = 126), the 5-year cancer
      specific survival was 100%. CONCLUSION: Renal oncocytic neoplasms have favorable
      oncological outcomes. Active surveillance is safe and is the preferred management
      for small (<=4 cm) oncocytic renal tumors in selected patients.

PMID- 29030074
TI  - A Survey of Morcellator Preference and Cost Comparison of the Lumenis VersaCut
      and Wolf Piranha Morcellators.
AB  - OBJECTIVE: To evaluate operating room (OR) costs associated with the 2 available
      morcellators in the United States in a matched cohort and to determine benign
      prostatic hyperplasia surgeon's morcellator preference. MATERIALS AND METHODS:
      Patients from 2013, the last year our institution exclusively used the VersaCut
      device, were matched 1:1 with the most recent patient cohort, utilizing the Wolf
      Piranha morcellator. Cost of morcellation including the expense of OR time and
      disposable instrument costs were calculated. A survey to the Endourological
      Society e-mail listserv was sent to determine morcellator preference. RESULTS: We
      identified 142 patients who underwent holmium laser enucleation of the prostate
      in 2013. When compared with the VersaCut group, morcellation efficiency (4.4 vs
      7.0 g/min, P <.01) and expense of OR time ($1420.80 vs $992.21, P <.005) both
      favored the Piranha morcellator system even when the costs of disposable
      instruments were factored into the analysis ($1338.81 vs $1637.50, P <.05). A
      total of 126 urologists responded to the survey. Of these, 56 (44.5%) perform
      transurethral prostate enucleations, which included 48 (86%) holmium. More
      endourologists use the VersaCut (n = 33, 59%) than the Piranha (n = 24, 43%)
      morcellator. Qualities that impacted the preference of morcellator included the
      preferred device is safer, faster, easier to use, reusable, and less expensive.
      CONCLUSION: We identified a significant improved efficiency and improved cost
      savings utilizing the Piranha morcellator even when controlling for disposable
      costs. Of the endourologists who responded to the survey, less than half perform
      transurethral enucleation. Morcellator preference is largely based on safety,
      efficiency, and ease of use, whereas cost and reusablility were of lesser
      importance.

PMID- 29030075
TI  - Giant Abdominal Wall Pseudocyst After Open Radical Cystectomy.
AB  - An abdominal wall pseudocyst refers to an encapsulated collection of fluid
      located superficially in the rectus abdominal muscles. This uncommon complication
      is diagnosed based on physical examination and computed tomography results.
      However, the etiology of its formation remains unclear. Abdominal wall pseudocyst
      can be effectively treated by surgery including complete excision of the cyst.
      Here, we report imaging findings of a giant pseudocyst in the anterior abdominal
      wall after an open radical cystectomy.

PMID- 29030076
TI  - Predictive Factors of De Novo Overactive Bladder After Artificial Urinary
      Sphincter Implantation in Men With Postprostatectomy Incontinence.
AB  - OBJECTIVE: To investigate the rates and predictive factors associated with the
      development of de novo overactive bladder (OAB) and to assess the effects of de
      novo OAB on surgical outcomes after an artificial urinary sphincter (AUS).
      MATERIALS AND METHODS: We performed a retrospective review of 132 patients with
      postprostatectomy incontinence who underwent AUS surgery. Urodynamic studies were
      performed during preoperative visits in all patients, and patients with OAB or
      neurogenic bladder were excluded. We assessed the development of de novo OAB
      based on patient symptoms. Treatment success was defined as no need for pads, and
      social continence was defined as the need for <=1pad per day at the end of the
      follow-up. A multivariate analysis was performed using a logistic regression
      model to assess predictors of de novo OAB. RESULTS: The rate of development of de
      novo OAB after surgery was 37.5%. The treatment success rate was significantly
      higher in the no-OAB group (72.4%) than in the de novo OAB group (55.4%) (P =
      .038). A low preoperative cystometric capacity of less than 300 mL (odds ratio
      5.27, confidence interval 1.02-27.28; P = .048) and pelvic irradiation (odds
      ratio 3.18, confidence interval 1.01-10.03; P = .049) were predictive factors of
      de novo OAB after AUS surgery. CONCLUSION: De novo OAB occurs commonly after AUS
      surgery, and the presence of de novo OAB adversely impacts treatment success. Low
      preoperative cystometric capacity of less than 300 mL and pelvic irradiation
      predict the occurrence of de novo OAB after AUS implantation.

PMID- 29030077
TI  - Corticomuscular coherence reflects somatosensory feedback gains during motor
      adaptation.
AB  - Beta-band corticomuscular coherence (CMC) observed between the sensorimotor
      cortex activity and contracting muscle is declaratively described as a
      neurophysiological reflection of sensorimotor binding. However, much remains
      unknown about the functional meaning of 'sensorimotor binding.' The efficacy of
      information binding in the sensorimotor system is assumed to be influenced by the
      gain of the feedback controller, which is regulated through a process that may in
      part be implemented in the primary sensorimotor cortex (SM1). Thus, we predicted
      that CMC is modulated together with feedback gains during motor learning. We
      examined this hypothesis using a hand-reaching adaptation task under a novel
      dynamical environment. CMC modulation was assessed before and after adaptation,
      and feedback gains were probed by long latency triggered muscle reactions.
      Overall, we found that CMC significantly decreased during the adaptation period,
      and such CMC decrease was associated with the decreased long latency reflexes.
      These results suggest that CMC has a related function to modulation of feedback
      gains. Our findings provided an electrophysiological hallmark of the sensorimotor
      binding process, which was stated as a function of CMC but poorly understood.

PMID- 29030079
TI  - Quantitative temporal changes in DTI values coupled with histological properties
      in cuprizone-induced demyelination and remyelination.
AB  - Diffusion tensor imaging (DTI) is widely used to evaluate microstructural
      variations in brain tissue. In particular, fractional anisotropy (FA), reflecting
      the magnitude and orientation of anisotropic water diffusion, allows us to detect
      pathological events in white matter. An ex vivo DTI study coupled with
      histological assessment is an efficient strategy to evaluate the myelination
      process, i.e. demyelination and remyelination. The relationship between DTI
      values and myelin content or the individual cellular components such as
      oligodendrocytes, microglia, and astrocytes during both processes of
      demyelination and remyelination are not well-understood. To address this issue,
      we employed a cuprizone-inducible demyelination mouse model. Demyelination can be
      induced in this model during cuprizone exposure and termination of cuprizone
      exposure induces remyelination. We fed the mice cuprizone-containing chow for 4
      weeks and then normal chow for an additional 4 weeks. The ex vivo DTI was
      performed to evaluate the white matter profiles observed by FA, mean diffusivity
      (MD), and radial diffusivity (RD) at both demyelinating and remyelinating time
      points, and then we evaluated histological properties at the same time points.
      The results indicated a gradual FA decrease during the cuprizone treatment (0, 2,
      3, 4 weeks). A lower peak was seen at 1 week after the normal chow was resumed,
      with recovery to baseline at 2 and 4 weeks. MD and RD showed an opposing pattern
      to that of FA. These DTI values were positively or negatively correlated with
      myelin content regardless of the status of the white matter. The RD value was
      more sensitive to myelination status than FA and MD. We have clarified the
      temporal changes in the DTI values coupled with histological properties over both
      the demyelination and remyelination processes.

PMID- 29030080
TI  - [Effectiveness of pelvic floor rehabilitation in erectile dysfunction: A
      literature review].
AB  - PURPOSE: The pelvic floor is now well known and its role in the mechanism of
      erection is demonstrated. We wanted to know what is the evidence of the
      effectiveness of perineal rehabilitation in erectile dysfunction. MATERIALS: An
      English search was performed in Google scholar and databases PubMed, Medline,
      Pedro with the keywords "pelvic floor, erectile dysfunction, impotence,
      physiotherapy, exercises, rehabilitation, PFMT". We have selected randomized
      clinical trials published in indexed journals. RESULTS: Six randomized trials
      were selected. Five of them have shown statistically and clinically significant
      effectiveness in populations of men with erectile dysfunction and various
      underlying pathologies. In the fifth trial, the difference in effectiveness was
      not statistically significant. At 3 months, the best-conducted study showed an
      average improvement of 7 points at IIEF-5 compared to the control group (P-value:
      0.004). Rehabilitation has not resulted in any adverse side effects. However,
      these studies were conducted in heterogeneous populations and the protocols for
      pelvic floor muscle strengthening rehabilitation differed from one study to
      another, making it impossible to formulate a specific recommendation for clinical
      practice. CONCLUSION: Based on the results of this literature review, perineal
      physiotherapy may have a role to play in the management of erectile dysfunction.

PMID- 29030081
TI  - Afterword.

PMID- 29030078
TI  - Evaluation of the prognostic value of neutrophil to lymphocyte ratio in patients
      with hypertriglyceridemia-induced acute pancreatitis.
AB  - INTRODUCTION: Recent studies attribute promising prognostic values to various
      inflammatory biomarkers in acute pancreatitis, including the following: the
      neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and red cell
      distribution width (RDW). We aimed to determine the performance of these
      biomarkers for detecting disease severity in patients with hypertriglyceridemia
      induced acute pancreatitis (HTG-AP). METHODS: We retrospectively reviewed 110
      patients with HTG-AP and compared the NLR, PLR, and RDW in different severity
      groups. We performed receiver-operating characteristic (ROC) analysis to identify
      the optimal cut-off value for NLR to predict severe AP. RESULTS: NLR was
      significantly higher in patients with severe AP than mild and moderately severe
      AP (14.6 vs. 6.9, p < 0.001), and higher with organ failure upon presentation
      (9.1 vs. 7.1, p = 0.026). After dichotomization by the optimal cut-off value of
      10 as determined by the ROC curve, the high-NLR group had a significantly longer
      length of stay (9.1 vs. 6.6 days, p = 0.001), duration of nil per os (4.9 vs. 3.7
      days, p = 0.007), and higher rates of complications, including systemic
      inflammatory response syndrome (81.5% vs. 44.6%, p = 0.001) and persistent acute
      kidney injury (25.9% vs. 3.6%, p < 0.001). High NLR independently predicted
      severe acute pancreatitis in multivariate analysis (Odds ratio 6.71, p = 0.019).
      CONCLUSION: NLR represents an inexpensive, readily available test with a
      promising value to predict disease severity in HTG-AP. Among the three
      inflammatory biomarkers, NLR has the highest discriminatory capacity for severe
      HTG-AP, with an optimal cut-off value of 10.

PMID- 29030082
TI  - ADX-47273, a mGlu5 receptor positive allosteric modulator, attenuates deficits in
      cognitive flexibility induced by withdrawal from 'binge-like' ethanol exposure in
      rats.
AB  - Repeated exposure to and withdrawal from ethanol induces deficits in spatial
      reversal learning. Data indicate that metabotropic glutamate 5 (mGlu5) receptors
      are implicated in synaptic plasticity and learning and memory. These receptors
      functionally interact with N-methyl-d-aspartate (NMDA) receptors, and activation
      of one type results in the activation of the other. We examined whether (S)-(4
      fluorophenyl)(3-(3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl)-piperidin-1-yl (ADX
      47273), a positive allosteric modulator (PAM) of mGlu5 receptor, attenuates
      deficits in reversal learning induced by withdrawal (11-13days) from 'binge-like'
      ethanol input (5.0g/kg, i.g. for 5days) in the Barnes maze (a spatial learning)
      task in rats. We additionally examined the effects of ADX-47273 on the expression
      of the NMDA receptors subunit, GluN2B, in the hippocampus and prefrontal cortex,
      on the 13th day of ethanol withdrawal. Herein, withdrawal from repeated ethanol
      administration impaired reversal learning, but not the probe trial. Moreover, ADX
      47273 (30mg/kg, i.p.) given prior to the first reversal learning trial for 3days
      in the Barnes maze, significantly enhanced performance in the ethanol-treated
      group. The 13th day of ethanol abstinence decreased the expression of the GluN2B
      subunit in the selected brain regions, but ADX-47273 administration increased it.
      In conclusion, positive allosteric modulation of mGlu5 receptors recovered
      spatial reversal learning impairment induced by withdrawal from 'binge-like'
      ethanol exposure. Such effect seems to be correlated with the mGlu5 receptors
      mediated potentiation of GluN2B-NMDA receptor mediated responses in the
      hippocampus and prefrontal cortex. Thus, our results emphasize the role of mGlu5
      receptor PAM in the adaptive learning impaired by ethanol exposure.

PMID- 29030083
TI  - Human bone marrow mesenchymal stem cells secrete endocannabinoids that stimulate
      in vitro hematopoietic stem cell migration effectively comparable to beta
      adrenergic stimulation.
AB  - Granulocyte colony-stimulating factor (G-CSF) is a well-known hematopoietic stem
      cell (HSC)-mobilizing agent used in both allogeneic and autologous
      transplantation. However, a proportion of patients or healthy donors fail to
      mobilize a sufficient number of cells. New mobilization agents are therefore
      needed. Endocannabinoids (eCBs) are endogenous lipid mediators generated in the
      brain and peripheral tissues and activate the cannabinoid receptors CB1 and CB2.
      We suggest that eCBs may act as mobilizers of HSCs from the bone marrow (BM)
      under stress conditions as beta-adrenergic receptors (Adrbeta). This study
      demonstrates that BM mesenchymal stem cells (MSCs) secrete anandamide (AEA) and 2
      arachidonylglycerol (2-AG) and the peripheral blood (PB) and BM microenvironment
      contain AEA and 2-AG. 2-AG levels are significantly higher in PB of the G-CSF
      treated group compared with BM plasma. BM mononuclear cells (MNCs) and CD34+ HSCs
      express CB1, CB2, and Adrbeta subtypes. CD34+ HSCs had higher CB1 and CB2
      receptor expression in G-CSF-untreated and G-CSF-treated groups compared with
      MSCs. MNCs but not MSCs expressed CB1 and CB2 receptors based on qRT-PCR and flow
      cytometry. AEA- and 2-AG-stimulated HSC migration was blocked by eCB receptor
      antagonists in an in vitro migration assay. In conclusion, components of the eCB
      system and their interaction with Adrbeta subtypes were demonstrated on HSCs and
      MSCs of G-CSF-treated and G-CSF-untreated healthy donors in vitro, revealing that
      eCBs might be potential candidates to enhance or facilitate G-CSF-mediated HSC
      migration under stress conditions in a clinical setting.

PMID- 29030085
TI  - Are emotionally driven and addictive-like eating behaviors the missing links
      between psychological distress and greater body weight?
AB  - There is now a large body of evidence suggesting a significant association
      between emotional discomfort management, disordered eating behaviors and weight
      status. In the field of overweight and obesity, emotionally driven eating habits
      that resemble addictive behaviors are considered as a risk factor. This study
      aimed to investigate in a large sample of French university students 1) the
      associations between self-reported levels of psychological distress (PD),
      emotional eating (EE), food addiction (FA) and Body Mass Index (BMI); and 2) the
      potential mediation effect of eating behaviors (EE and FA) between PD and BMI.
      The responses of 1051 students (76.3% females) to self-reports assessing PD
      (Perceived Stress Scale, Hospital Anxiety and Depression Scale), EE (Intuitive
      Eating Scale-2) and FA (modified Yale Food Addiction Scale) were analysed.
      Associations between variables (Spearman correlation) and group comparisons by
      sex and BMI categories (Student's t tests/ANOVA) were tested, followed by
      Structural Equation Modeling (SEM) by sex. Among females and males, EE and FA
      scores were positively inter-related and correlated with PD scores and BMI.
      Moreover, among females and males, SEM showed that both EE and FA acts as
      mediators between PD and BMI. Hence, among educated young adults, using food
      consumption for down-regulating negative mood places the individual at risk for
      overweight and obesity. This study further emphasizes the necessity to take into
      account emotionally driven and addictive-like eating behaviors in interventions
      for promoting healthy eating and weight management.

PMID- 29030084
TI  - Characterization and use of the novel human multiple myeloma cell line MC-B11/14
      to study biological consequences of CRISPR-mediated loss of immunoglobulin A
      heavy chain.
AB  - The genetic abnormalities underlying multiple myeloma (MM) are notoriously
      complex and intraclonal heterogeneity is a common disease feature. In the current
      study, we describe the establishment of a monoclonal immunoglobulin A (IgA) kappa
      (kappa) MM cell line designated MC-B11/14. Cytogenetic and fluorescence in situ
      hybridization analyses of the original and relapse patient samples revealed that
      the MM clone was nonhyperdiploid and possessed an 11;14 chromosomal
      translocation. The MC-B11/14 cell line, established from the relapse sample, is
      tetraploid and houses the t(11;14) abnormality. Given our long-standing interest
      in Ig function and secretion, we next used CRISPR technology to knock out IgA
      heavy-chain expression in the MC-B11/14 cells to assess the biological
      consequences of converting this cell line to one only expressing kappa light
      chains. As expected, secretion of intact IgA was undetectable from MC-B11/14IgA-
      cells. Sensitivity to pomalidomide treatment was similar between the MC-B11/14WT
      and MC-B11/14IgA- cells; however, MC-B11/14IgA- cells were found to be
      significantly more resistant to bortezomib treatment. This study describes the
      establishment of a new human MM cell line tool with which to study disease
      biology and the use of CRISPR technology to create a potentially useful model
      with which to study MM light-chain escape.

PMID- 29030086
TI  - Impact of type, size and shape of plates on hospital patients' perceptions of the
      quality of meals and satisfaction with foodservices.
AB  - Hospital meals are important for supporting nutrition goals and the overall
      hospital experience. The aim of this study was to assess if patients' perceptions
      of quality attributes of hot meals were impacted by the type of plate on which
      the meal was served. Eligible patients selected from medical and/or surgical
      wards at a 929 bed acute care hospital were randomised to receive hot meals
      served on either ceramic or disposable plates at eight evening meals. Patients
      from a multi-centre trial of pre-packaged meals where re-thermalised meals were
      presented on a variety of colour and shaped disposable plates were included in a
      second phase. Patient assessment of meal quality was undertaken using the Meal
      Assessment Tool (MAT)(Hannan-Jones & Capra, 2017) with data collected by
      interview. In phase one, 137 eligible patients competed the MAT (response 46.8%),
      with results showing no significant difference in the rating of appearance,
      quality, expectations or satisfaction when meals were served on disposable or
      ceramic plates. In phase two data were collected from 6189 patients (response
      47.4%). No practical difference in rating of meals was found in relation to
      colour and sectioning of plates, however a statistical but non-practical
      difference was found regarding plate shape, with meals served on
      oblong/rectangular plates rated more positively. Of 3078 comments made concerning
      the meals, 99 (3.2%) concerned the plates on which the meals were served. This
      study has shown that quality, appearance and taste of meals, rather than the
      serving ware are important to patients. Findings suggest that attending to other
      quality aspects of meals may be far more important than the plate itself, and
      deserve attention.

PMID- 29030087
TI  - Current insights on the role of iron and copper dyshomeostasis in the
      pathogenesis of bilirubin neurotoxicity.

PMID- 29030088
TI  - Effects of N-acetylcysteine on isolated skeletal muscle contractile properties
      after an acute bout of aerobic exercise.
AB  - AIMS: The current study tested the hypotheses that 1) an acute bout of aerobic
      exercise impairs isolated skeletal muscle contractile properties and 2) N
      acetylcysteine (a thiol antioxidant; NAC) administration can restore the impaired
      muscle contractility after exercise. MAIN METHODS: At rest or immediately after
      an acute bout of aerobic exercise, extensor digitorum longus (EDL) and soleus
      muscles from male Wistar rats were harvested for ex vivo skeletal muscle
      contraction experiments. Muscles from exercised animals were incubated in Krebs
      Ringer's buffer in absence or presence of 20mM of NAC. Force capacity and fatigue
      properties were evaluated. KEY FINDINGS: Exercised EDL and soleus displayed lower
      force production across various stimulation frequencies (p<0.001), indicating
      that skeletal muscle force production was impaired after an acute bout of
      exercise. However, NAC treatment restored the loss of force production in both
      EDL and soleus after fatiguing exercise (p<0.05). Additionally, NAC treatment
      increased relative force production at different time points during a fatigue
      induced protocol, suggesting that NAC treatment mitigates fatigue induced by
      successive contractions. SIGNIFICANCE: NAC treatment improves force capacity and
      fatigue properties in ex vivo skeletal muscle from rats submitted to an acute
      bout of aerobic exercise.

PMID- 29030089
TI  - Knockdown of HIF-1alpha inhibits the proliferation and migration of outer root
      sheath cells exposed to hypoxia in vitro: An involvement of Shh pathway.
AB  - AIMS: Outer root sheath (ORS) is a highly proliferative component of a hair
      follicle. This study is performed to investigate whether hypoxia-induced
      elevation of hypoxia-inducible factor (HIF)-1alpha, a transcriptional activator,
      contributes to the outgrowth of ORS cells in vitro. MAIN METHODS: Hair follicles
      with intact ORS collected from 4-month old male American minks were cultured in
      normoxic or hypoxic condition (3% oxygen) for 7days. Primary ORS cells isolated
      from the mink hair follicles were exposed to hypoxia for 12, 24 or 48h, and their
      proliferation was analyzed with immunofluorescence assay using anti-proliferating
      cell nuclear antigen (PCNA) antibody. The migratory ability of ORS cells was
      detected via the transwell chamber. The endogenous HIF-1alpha was knocked down
      with its specific siRNA in ORS cells. KEY FINDINGS: Hypoxic exposure induced an
      elevation of HIF-1alpha in ex vivo cultured hair follicles. The mRNA and protein
      levels of sonic hedgehog (Shh), Shh receptor Patched 1, Smoothened and glioma
      associated oncogene homologue 1 were upregulated. In vitro, hypoxia induced an
      increase in HIF-1alpha in ORS cells. Further, under hypoxic condition, the number
      of PCNA-positive cells was increased, and more cells migrated towards high serum
      media. Hypoxia-enhanced proliferation and migration of ORS cells were suppressed
      either by HIF-1alpha siRNA or by pharmacological inhibitors of Shh pathway,
      cyclopamine and GANT61. The activation of Shh pathway was attenuated in HIF
      1alpha-silenced ORS cells under hypoxic condition. SIGNIFICANCE: Our work
      demonstrates a direct role of activated HIF-1/Shh biological axis in sustaining
      the development of ORS in vitro.

PMID- 29030090
TI  - Differential expression of CCR4 in primary cutaneous gamma/delta (gamma/delta) T
      cell lymphomas and mycosis fungoides: Significance for diagnosis and therapy.

PMID- 29030091
TI  - Clinical characteristics of acute promyelocytic leukemia with the STAT5B-RARA
      fusion gene.

PMID- 29030092
TI  - A Phase II Study of CLAG Regimen Combined With Imatinib Mesylate for Relapsed or
      Refractory Acute Myeloid Leukemia.
AB  - INTRODUCTION: No standard salvage chemotherapy regimen is available for relapsed
      or refractory (RR) acute myeloid leukemia (AML). Preclinical data have suggested
      synergy in vitro between cytarabine and imatinib mesylate (IM) on AML cell growth
      inhibition. After demonstrating the safety and feasibility in a phase I study, we
      conducted a phase II clinical study of CLAG (cladribine, cytarabine, granulocyte
      colony-stimulating factor) regimen combined with IM for patients with RR-AML.
      PATIENTS AND METHODS: We performed a single-institution 2-stage phase II study.
      The primary endpoint was the remission rate measured using the standard AML
      response criteria. The secondary endpoints included overall survival (OS) and
      progression-free survival (PFS). RESULTS: From August 2009 to April 2011, 38
      patients were treated at the Moffitt Cancer Center. Their median age was 62 years
      (range, 26-79 years). Of the 38 patients, 7 (18%) had refractory AML, 19 (50%)
      had early relapse, and 12 (32%) had late relapse. At the original diagnosis, only
      2 patients had favorable risk factors, 18 had intermediate risk, and 16 had poor
      risk; for 2 patients, the karyotype was missing. The overall response rate for
      all 38 evaluable patients was 37%. The median OS was 11.1 months (95% CI, 4.8
      13.4 months), the median PFS was 4.9 months (95% CI, 1.6-11.7 months). Among the
      responders, 8 of 14 patients subsequently underwent allogeneic hematopoietic cell
      transplantation. CONCLUSION: CLAG plus IM was well tolerated, with encouraging
      signs of activity in patients with poor-risk AML.

PMID- 29030093
TI  - Estimating past inhalation exposure to asbestos: A tool for risk attribution and
      disease screening.
AB  - INTRODUCTION: Late presentation is common in mesothelioma. Reliable assessment of
      past exposure to asbestos is a necessary first step for risk attribution and for
      the development of a future screening programme. Such a programme could maximise
      access to trials of novel therapies and would pave the way for development of
      novel chemoprophylaxis strategies. This paper describes a method for individual
      exposure reconstruction along with data from a validation study. METHODS: The
      exposure assessment method uses only descriptive information about the
      circumstances of the work that could be obtained from questioning the worker. The
      assessment is based on the tasks carried out and includes parameters for
      substance emission potential, activity emission potential, the effectiveness of
      any local control measures, passive emission, the fractional time the asbestos
      source is active and the efficiency of any respiratory protection worn. RESULTS:
      There was a good association between the estimated and measured exposure levels.
      Pearson's correlation coefficient between the log-transformed measurements and
      estimates from the model was 0.86, and 95% of the estimated individual values
      were within about a factor of ten of the associated measured value. The method
      described would be suitable for pre-selecting individuals at high risk of
      malignant pleural mesothelioma for screening using appropriate tools and/or
      enrolment in clinical trials of chemo-prophylaxis. DISCUSSION: This method is of
      potential clinical value in developing novel treatment approaches for
      mesothelioma. Pilot studies to test this approach are urgently needed.

PMID- 29030095
TI  - Postoperative Rehabilitation Following Thumb Base Surgery: A Systematic Review of
      the Literature.
AB  - OBJECTIVE: To provide an overview of rehabilitation for patients who underwent
      first carpometacarpal joint (CMC-1) arthroplasty, with emphasis on early active
      mobilization. DATA SOURCES: PubMed/MEDLINE, Embase, CINAHL, and Cochrane were
      searched. STUDY SELECTION: Articles written in English that described the
      postoperative regimen (including immobilization period/method and/or description
      of exercises/physical therapy, follow-up 6wk) on CMC-1 arthroplasty were
      included. DATA EXTRACTION: The Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses statement was used as guidance in this review, and
      methodological quality was assessed using the Effective Public Health Practice
      Project quality assessment tool. Randomized studies were additionally scored
      using the Physiotherapy Evidence Database scale. DATA SYNTHESIS: Twenty-seven
      studies were included consisting of 1015 participants, in whom 1118 surgical
      procedures were performed. A summary of the components of postoperative
      rehabilitation used in the included studies of CMC-1 osteoarthritis is presented
      for different surgical interventions. We found that early active recovery
      (including short immobilization, early initiation of range of motion and strength
      exercises) provides positive outcomes for pain, limitations in activities of
      daily living, and grip and pinch strength, but comparative studies are lacking.
      Furthermore, 3 postoperative exercises/therapy phases were identified in the
      literature-the acute phase, the unloaded phase, and the functional phase-but
      again comparative studies are lacking. CONCLUSIONS: Early active recovery is used
      more often in the literature and does not lead to worse outcomes or more
      complications. This systematic review provides guidance for clinicians in the
      content of postoperative rehabilitation for CMC-1 arthroplasty. The review also
      clearly identifies the almost complete lack of high-quality comparative studies
      on postoperative rehabilitation after CMC-1 arthroplasty.

PMID- 29030094
TI  - Particulate matter air pollution, physical activity and systemic inflammation in
      Taiwanese adults.
AB  - BACKGROUND: The protective effects of physical activity (PA) against chronic
      disease can be partially ascribed to its anti-inflammatory effects. On the other
      hand, long-term exposure to particulate matter with an aerodynamic diameter less
      than 2.5MUm (PM2.5) may induce systemic inflammation. OBJECTIVE: To investigate
      the joint effects of habitual PA and long-term exposure to PM2.5 on systemic
      inflammation in a large cohort of Taiwanese adults. METHODS: We studied 359,067
      adult participants from a cohort consisting of Taiwanese residents who
      participated in a standard medical examination program from 2001 to 2014.
      Peripheral white blood cell (WBC) and differential counts were measured as
      indicators of systemic inflammation. Two-year average concentration of PM2.5 was
      estimated at each participant's address using a satellite-based spatio-temporal
      model. Habitual PA level was assessed by questionnaire (inactive, low, moderate
      and high). Mixed-effects linear regression model was used to examine the
      associations of WBC counts with PM2.5 and PA. RESULTS: Compared with inactive
      participants, those with low, moderate or high PA levels had 0.36% [95%
      confidence interval (CI): 0.31%, 0.41%], 0.70% (95%CI: 0.65%, 0.76%) and 1.16%
      (95%CI: 1.11%, 1.22%) lower WBC counts, respectively, after adjusting for PM2.5
      exposure and a wide range of confounders. Long-term PM2.5 exposure was associated
      with increased WBC counts at all PA levels. Analyses for differential counts
      generated similar results. No significant interaction was observed between PA and
      PM2.5 exposure (P for interaction=0.59). CONCLUSIONS: Habitual PA was associated
      with statistically significant lower markers of systemic inflammation across
      different levels of PM2.5. Effects of PA and PM2.5 exposure on systemic
      inflammation are independent.

PMID- 29030096
TI  - Medical Safety Huddles in Rehabilitation: A Novel Patient Safety Strategy.
AB  - OBJECTIVE: To describe the implementation process, outcomes, and lessons learned
      in the implementation of medical safety huddles, a novel patient safety
      monitoring strategy that promotes physician engagement with patient safety.
      DESIGN: Single-center observational study. SETTING: Brain and spinal cord injury
      rehabilitation program at an urban, academic adult rehabilitation hospital.
      PARTICIPANTS: Physicians associated with the program (N=18). INTERVENTIONS:
      Weekly physicians' safety huddles were implemented to review, anticipate, and
      address patient safety issues. MAIN OUTCOME MEASURES: Main outcome measures were
      the number and nature of identified and anticipated patient safety incidents,
      actions taken, and physician attendance during huddles. The number of adverse
      events in the program before and after huddle implementation were secondary
      measures. RESULTS: Over a 7-month period, average physician attendance at medical
      huddles was 76.0%. There were 1.0+/-0.8 patient safety incidents and 3.2+/-2.1
      anticipated patient safety issues identified in each weekly huddle. Most patient
      safety incidents identified were clinical administrative and clinical process
      related, which differed from information gathered from the organization's
      preexisting patient safety monitoring strategies. A total of 79 actions, or 3.3+/
      1.8 actions per huddle, were taken in response to improve patient safety for the
      program. Adverse events decreased from 31.2 (95% confidence interval [CI], 27.0
      35.3) to 22.9 per month (95% CI, 19.3-26.5) after implementation. CONCLUSIONS:
      Medical safety huddles are a novel strategy to engage physicians in patient
      safety and organizational quality improvement. They have the potential to enhance
      organizational anticipation of safety risks by supplementing existing methods.
      Other rehabilitation settings may wish to consider implementing and evaluating
      similar huddles into their existing patient safety and quality improvement
      frameworks.

PMID- 29030097
TI  - Transient vimentin expression during the embryonic development of the chicken
      cerebellum.
AB  - Complex morphogenetic events, critical for the development of normal cerebellum
      foliation and layering, are known to involve type III intermediate filament
      protein such as vimentin expressed by Bergmann glia. The present study aimed to
      determine aspects of intermediate and late embryonic pattern of vimentin
      expression during the corticogenesis of chicken cerebellum at embryonic days 10
      19 (E10-E19), using single and double immunohistochemistry/immunofluorescence.
      Vimentin expression showed partial co-localization with the glial markers GFAP
      and BLBP. Within cerebellar cortex, vimentin+ fibers were first found within
      lobules I and X (E10) and gradually extended to all folia (E15-E17), located
      within the external granule (EGL) the molecular cell layer, showing a radial
      orientation towards the inner granular layer and the cerebellar white matter
      oriented longitudinally. Interestingly, within the immature fissures base of most
      lobules, vimentin+ fibers radiate in a fan shape. Short-term BrdU experiments
      revealed that EGL cell proliferation was higher in the fissure base compared to
      folia apex. In addition, following 24-h survival, BrdU+ cells were found in close
      association to vimentin+ fibers in the EGL pre-migratory zone and within immature
      molecular layer. Paralleling cerebellum development, vimentin expression
      gradually extended to all folia sub-regions (base, wall, apex), but, at day E19,
      it was mainly confined to the folia apex and secondary fissure base. Taken
      together our data further support the possible role of vimentin+ fibers in the
      structural events of cerebellum corticogenesis, suggesting the participation of
      radial/Bergmann glia in chicken cerebellum foliation, similarly to that described
      for mammalian cerebellum morphogenesis.

PMID- 29030099
TI  - A Comprehensive Review of Hirudiniasis: From Historic Uses of Leeches to Modern
      Treatments of Their Bites.
AB  - Exposure to leeches in the wilderness setting is common. Leeches may attach
      themselves to exposed skin or pass through one of the body's orifices and attach
      internally. The condition of leech attachment is known as hirudiniasis, which can
      result in serious morbidity and, rarely, mortality. A comprehensive review of the
      literature was performed to detail the prevention of leech attachment, as well as
      both anecdotal and studied methods of removal. Complications from leech
      attachments include ongoing bleeding, wound infection, and poor wound healing.
      Although medicinal leeches are the most well-studied variety, this review
      examines all aspects of leech attachment, prevention, and management.

PMID- 29030098
TI  - MetaNetter 2: A Cytoscape plugin for ab initio network analysis and metabolite
      feature classification.
AB  - Metabolomics frequently relies on the use of high resolution mass spectrometry
      data. Classification and filtering of this data remain a challenging task due to
      the plethora of complex mass spectral artefacts, chemical noise, adducts and
      fragmentation that occur during ionisation and analysis. Additionally, the
      relationships between detected compounds can provide a wealth of information
      about the nature of the samples and the biochemistry that gave rise to them. We
      present a biochemical networking tool: MetaNetter 2 that is based on the original
      MetaNetter, a Cytoscape plugin that creates ab initio networks. The new version
      supports two major improvements: the generation of adduct networks and the
      creation of tables that map adduct or transformation patterns across multiple
      samples, providing a readout of compound relationships. We have applied this tool
      to the analysis of adduct patterns in the same sample separated under two
      different chromatographies, allowing inferences to be made about the effect of
      different buffer conditions on adduct detection, and the application of the
      chemical transformation analysis to both a single fragmentation analysis and an
      all-ions fragmentation dataset. Finally, we present an analysis of a dataset
      derived from anaerobic and aerobic growth of the organism Staphylococcus aureus
      demonstrating the utility of the tool for biological analysis.

PMID- 29030100
TI  - Antimicrobial susceptibility profiles of oral Treponema species.
AB  - Treponemes occur in the microflora of the dental plaque. Certain Treponema
      species that are frequently isolated from chronic periodontitis lesions are
      involved in its initiation and progression. In addition to mechanical
      instrumentation, antimicrobial agents are used as an adjunctive treatment
      modality for periodontitis. Despite its importance for successful antimicrobial
      treatment, information about susceptibility is limited for Treponema species. The
      aim of this study was to assess the susceptibility of Treponema denticola
      strains, Treponema socranskii, and Treponema vincentii to eleven antimicrobial
      agents. The minimum inhibitory and minimum bactericidal concentrations of these
      antimicrobial agents revealed strain-specific variation. Doxycycline,
      minocycline, azithromycin, and erythromycin were effective against all Treponema
      species tested in this study, whereas fluoroquinolones only exhibited an
      equivalent effectiveness on T. socranskii. The susceptibility of one T. denticola
      strain, T. socranskii, and T. vincentii to kanamycin was influenced by prior
      exposure to aerobic conditions. The susceptibility to quinolone drugs varied
      among strains of T. denticola, although they share an amino acid sequence
      identity of greater than 99% for DNA gyrase (type II topoisomerase) subunit A. In
      addition, an ATP-binding cassette (ABC) transporter inhibitor assay for T.
      denticola indicated that the transport of quinolone drugs is partially related to
      this transporter, although there may be parallel transport mechanisms. Our
      results provide important insights into antimicrobial agent-Treponema dynamics
      and establish a basis for developing an appropriate adjunctive therapy for
      periodontal disease.

PMID- 29030102
TI  - Lolium perenne peptides for treatment of grass pollen allergy: A randomized,
      double-blind, placebo-controlled clinical trial.

PMID- 29030101
TI  - Genome-wide association study and meta-analysis in multiple populations
      identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic
      risk factor for food allergy.
AB  - BACKGROUND: Peanut allergy (PA) is a complex disease with both environmental and
      genetic risk factors. Previously, PA loci were identified in filaggrin (FLG) and
      HLA in candidate gene studies, and loci in HLA were identified in a genome-wide
      association study and meta-analysis. OBJECTIVE: We sought to investigate genetic
      susceptibility to PA. METHODS: Eight hundred fifty cases and 926 hyper-control
      subjects and more than 7.8 million genotyped and imputed single nucleotide
      polymorphisms (SNPs) were analyzed in a genome-wide association study to identify
      susceptibility variants for PA in the Canadian population. A meta-analysis of 2
      phenotypes (PA and food allergy) was conducted by using 7 studies from the
      Canadian, American (n = 2), Australian, German, and Dutch (n = 2) populations.
      RESULTS: An SNP near integrin alpha6 (ITGA6) reached genome-wide significance
      with PA (P = 1.80 * 10-8), whereas SNPs associated with Src kinase-associated
      phosphoprotein 1 (SKAP1), matrix metallopeptidase 12 (MMP12)/MMP13, catenin
      alpha3 (CTNNA3), rho GTPase-activating protein 24 (ARHGAP24), angiopoietin 4
      (ANGPT4), chromosome 11 open reading frame (C11orf30/EMSY), and exocyst complex
      component 4 (EXOC4) reached a threshold suggestive of association (P <= 1.49 * 10
      6). In the meta-analysis of PA, loci in or near ITGA6, ANGPT4, MMP12/MMP13,
      C11orf30, and EXOC4 were significant (P <= 1.49 * 10-6). When a phenotype of any
      food allergy was used for meta-analysis, the C11orf30 locus reached genome-wide
      significance (P = 7.50 * 10-11), whereas SNPs associated with ITGA6, ANGPT4,
      MMP12/MMP13, and EXOC4 and additional C11orf30 SNPs were suggestive (P <= 1.49 *
      10-6). Functional annotation indicated that SKAP1 regulates expression of CBX1,
      which colocalizes with the EMSY protein coded by C11orf30. CONCLUSION: This study
      identifies multiple novel loci as risk factors for PA and food allergy and
      establishes C11orf30 as a risk locus for both PA and food allergy. Multiple genes
      (C11orf30/EMSY, SKAP1, and CTNNA3) identified by this study are involved in
      epigenetic regulation of gene expression.

PMID- 29030103
TI  - Combining region- and network-level brain-behavior relationships in a structural
      equation model.
AB  - Brain-behavior associations in fMRI studies are typically restricted to a single
      level of analysis: either a circumscribed brain region-of-interest (ROI) or a
      larger network of brain regions. However, this common practice may not always
      account for the interdependencies among ROIs of the same network or potentially
      unique information at the ROI-level, respectively. To account for both sources of
      information, we combined measurement and structural components of structural
      equation modeling (SEM) approaches to empirically derive networks from ROI
      activity, and to assess the association of both individual ROIs and their
      respective whole-brain activation networks with task performance using three
      large task-fMRI datasets and two separate brain parcellation schemes. The results
      for working memory and relational tasks revealed that well-known ROI-performance
      associations are either non-significant or reversed when accounting for the ROI's
      common association with its corresponding network, and that the network as a
      whole is instead robustly associated with task performance. The results for the
      arithmetic task revealed that in certain cases, an ROI can be robustly associated
      with task performance, even when accounting for its associated network. The SEM
      framework described in this study provides researchers additional flexibility in
      testing brain-behavior relationships, as well as a principled way to combine ROI-
      and network-levels of analysis.

PMID- 29030104
TI  - FReM - Scalable and stable decoding with fast regularized ensemble of models.
AB  - Brain decoding relates behavior to brain activity through predictive models.
      These are also used to identify brain regions involved in the cognitive
      operations related to the observed behavior. Training such multivariate models is
      a high-dimensional statistical problem that calls for suitable priors. State of
      the art priors -eg small total-variation- enforce spatial structure on the maps
      to stabilize them and improve prediction. However, they come with a hefty
      computational cost. We build upon very fast dimension reduction with spatial
      structure and model ensembling to achieve decoders that are fast on large
      datasets and increase the stability of the predictions and the maps. Our
      approach, fast regularized ensemble of models (FReM), includes an implicit
      spatial regularization by using a voxel grouping with a fast clustering
      algorithm. In addition, it aggregates different estimators obtained across splits
      of a cross-validation loop, each time keeping the best possible model.
      Experiments on a large number of brain imaging datasets show that our combination
      of voxel clustering and model ensembling improves decoding maps stability and
      reduces the variance of prediction accuracy. Importantly, our method requires
      less samples than state-of-the-art methods to achieve a given level of prediction
      accuracy. Finally, FreM is much faster than other spatially-regularized methods
      and, in addition, it can better exploit parallel computing resources.

PMID- 29030106
TI  - The Shift From Sentinel Lymph Node Biopsy Performed Either Before or After
      Neoadjuvant Systemic Therapy in the Clinical Negative Nodes of Breast Cancer
      Patients. Results, and the Advantages and Disadvantages of Both Procedures.
AB  - BACKGROUND: In patients with breast cancer who are candidates for neoadjuvant
      therapy (NAT), the timing of when to perform sentinel lymph node biopsy (SLNB)
      remains under discussion. The aim of this study was to compare the advantages and
      disadvantages of SLNB performed before and after NAT. PATIENTS AND METHODS: One
      hundred seventy-two patients, T1c to T3 and N0 (clinically and according to
      ultrasound) candidates for NAT were included. We compared the outcomes of 2
      groups: (1) 122 patients of whom SLNB was performed before NAT (pre-NAT) from
      December 2006 to April 2014; and (2) 50 patients with SLNB performed after NAT
      (post-NAT) from May 2014 to July 2016. RESULTS: Both groups were homogeneous in
      baseline patient characteristics. The SLNB was positive in 50 patients [41.7%]
      (33 macrometastases [66%] and 17 micrometastases [34%]) versus 6 patients [12%]
      (5 macrometastases [83.3%] and 1 micrometastases [16.7%]) in pre- and post-NAT
      groups, respectively. The lymphadenectomy was performed in 34 patients [28.3%]
      versus 4 patients [8%], with an odds ratio of 3.48 (95% confidence interval, 1.3
      9.3). The recurrences in the pre-NAT group after a median follow-up of 62 months
      were 12 systemic, 2 local and systemic, and none axillary. In the post-NAT group
      were no recurrences after a median follow-up of 16 months. Finally, SLNB after
      NAT reduces the delay in starting NAT from 24 to 14 days (medians; P < .001) and
      the identification of the SLNB was in 122 patients [100%] versus 49 patients
      [98%]. CONCLUSION: SLNB performed after NAT significantly reduces the rate of
      lymphadenectomies without any increase in recurrences at early follow-up.
      Furthermore, it allows systemic treatment to be started earlier without
      interfering in the SLNB identification rate.

PMID- 29030107
TI  - Ammodytin L is the main cardiotoxic component of the Vipera ammodytes ammodytes
      venom.
AB  - Venom of the nose-horned viper (V. a. ammodytes) as also venoms of some related
      European viperids can induce also cardiotoxic effects in mammals. In this work we
      demonstrated that the protein in the V. a. ammodytes venom acting on heart is a
      myotoxic secreted phospholipase A2 analogue ammodytin L (AtnL). In the isolated
      perfused rat heart AtnL induced significant and irreversible cardiotoxicity
      characterized by atrioventricular (AV) blockade. This venom protein induced
      appearance of high levels of creatine kinase, lactate dehydrogenase, aspartate
      aminotransferase and troponin I in the sinus effluent of the isolated heart,
      indicative for myocardial damage, which is obviously the primary cause of its
      cardiotoxic action. Gel filtration chromatography subfractions C1 and C2 of the
      V. a. ammodytes venom harboured most of the venom cardiotoxicity. As we showed,
      just these two subfractions contained also AtnL. Subfraction C1 in the final CF
      concentration 11.3 MUg/mL (containing 3.1 MUg/mL AtnL) induced a complete cardiac
      arrest while subfraction C2 in the final CF concentration 6.0 MUg/mL (containing
      0.8 MUg/mL AtnL) and the pure AtnL (1.0 MUg/mL) did not. Contrary to AtnL,
      subfraction C1 at 11.3 MUg/mL was not able to induce the AV blockade. This
      exposed the only other cardiotoxic subfractions-specific venom protein, a
      cysteine-rich secretory protein (CRISP), as an additional venom component
      potentially involved in modulation of the heart activity. Cardiotoxicity reported
      in some cases of the adder (V. berus) venom and the asp viper (V. aspis) venom
      poisonings may be assigned to AtnL in these venoms.

PMID- 29030105
TI  - Definition and characterization of an extended multiple-demand network.
AB  - Neuroimaging evidence suggests that executive functions (EF) depend on brain
      regions that are not closely tied to specific cognitive demands but rather to a
      wide range of behaviors. A multiple-demand (MD) system has been proposed,
      consisting of regions showing conjoint activation across multiple demands.
      Additionally, a number of studies defining networks specific to certain cognitive
      tasks suggest that the MD system may be composed of a number of sub-networks each
      subserving specific roles within the system. We here provide a robust definition
      of an extended MDN (eMDN) based on task-dependent and task-independent functional
      connectivity analyses seeded from regions previously shown to be convergently
      recruited across neuroimaging studies probing working memory, attention and
      inhibition, i.e., the proposed key components of EF. Additionally, we
      investigated potential sub-networks within the eMDN based on their connectional
      and functional similarities. We propose an eMDN network consisting of a core
      whose integrity should be crucial to performance of most operations that are
      considered higher cognitive or EF. This then recruits additional areas depending
      on specific demands.

PMID- 29030108
TI  - Enclosure utilisation and activity budgets of disabled Malayan sun bears
      (Helarctos malayanus).
AB  - Captive bears are housed in environments that differ greatly from their natural
      habitat, restricting their ability to perform normal species-specific behaviours.
      This may be detrimental to welfare, with disabled individuals at particular risk.
      The effect of physical disability on behaviour and enclosure utilisation was
      assessed in 12 adult Malayan sun bears (Helarctos malayanus) using 10min interval
      scan sampling. Amputees spent less time performing locomotor behaviours than able
      bodied bears, used their enclosures less evenly, but did not exhibit obvious
      stereotypies. This was possibly due to the increased energy demands of
      locomotion, or residual pain in amputated limbs. Amputees spent less time
      grooming, but did not differ in time spent climbing compared with non-amputees.
      Partially sighted bears did not differ from able-bodied controls in enclosure use
      or behaviour. Age was positively correlated with stereotypical behaviour, and
      negatively correlated with maintenance and resting. Medication use was associated
      with more resting and grooming, and reduced stereotypy. The findings suggest that
      enclosures for amputees can be smaller than those for able-bodied bears, but
      should still contain a variety of climbing structures. Partially sighted bears
      fare well in enclosures designed for able-bodied bears, not requiring any special
      provision.

PMID- 29030109
TI  - Social information changes stress hormone receptor expression in the songbird
      brain.
AB  - Social information is used by many vertebrate taxa to inform decision-making,
      including resource-mediated movements, yet the mechanisms whereby social
      information is integrated physiologically to affect such decisions remain
      unknown. Social information is known to influence the physiological response to
      food reduction in captive songbirds. Red crossbills (Loxia curvirostra) that were
      food reduced for several days showed significant elevations in circulating
      corticosterone (a "stress" hormone often responsive to food limitation) only if
      their neighbors were similarly food restricted. Physiological responses to
      glucocorticoid hormones are enacted through two receptors that may be expressed
      differentially in target tissues. Therefore, we investigated the influence of
      social information on the expression of the mineralocorticoid receptor (MR) and
      glucocorticoid receptor (GR) mRNA in captive red crossbill brains. Although the
      role of MR and GR in the response to social information may be highly complex, we
      specifically predicted social information from food-restricted individuals would
      reduce MR and GR expression in two brain regions known to regulate hypothalamic
      pituitary-adrenal (HPA) activity - given that reduced receptor expression may
      lessen the efficacy of negative feedback and release inhibitory tone on the HPA.
      Our results support these predictions - offering one potential mechanism whereby
      social cues could increase or sustain HPA-activity during stress. The data
      further suggest different mechanisms by which metabolic stress versus social
      information influence HPA activity and behavioral outcomes.

PMID- 29030110
TI  - Where and what TMS activates: Experiments and modeling.
AB  - BACKGROUND: Despite recent developments in navigation and modeling techniques,
      the type and location of the structures that are activated by transcranial
      magnetic stimulation (TMS) remain unknown. OBJECTIVE: We studied the
      relationships between electrophysiological measurements and electric fields
      induced in the brain to locate the TMS activation site. METHODS: The active and
      resting motor thresholds of the first dorsal interosseous muscle were recorded in
      19 subjects (7 female, 12 male, age 22 +/- 4 years) using anteromedially oriented
      monophasic TMS at multiple locations over the left primary motor cortex (M1).
      Structural MR images were used to construct electric field models of each
      subject's head and brain. The cortical activation site was estimated by finding
      where the calculated electric fields best explained the coil-location dependency
      of the measured MTs. RESULTS: The experiments and modeling showed individual
      variations both in the measured motor thresholds (MTs) and in the computed
      electric fields. When the TMS coil was moved on the scalp, the calculated
      electric fields in the hand knob region were shown to vary consistently with the
      measured MTs. Group-level analysis indicated that the electric fields were
      significantly correlated with the measured MTs. The strongest correlations (R2 =
      0.69), which indicated the most likely activation site, were found in the ventral
      and lateral part of the hand knob. The site was independent of voluntary
      contractions of the target muscle. CONCLUSION: The study showed that TMS combined
      with personalized electric field modeling can be used for high-resolution mapping
      of the motor cortex.

PMID- 29030112
TI  - Sailing in a sea of disbelief: In vivo measurements of transcranial electric
      stimulation in human subcortical structures.

PMID- 29030111
TI  - Double-blind, proof-of-concept (POC) trial of Low-Field Magnetic Stimulation
      (LFMS) augmentation of antidepressant therapy in treatment-resistant depression
      (TRD).
AB  - BACKGROUND: Low-Field Magnetic Stimulation (LFMS) is a novel, non-invasive, sub
      threshold neuromodulation technique, shown in preliminary studies to have
      immediate mood elevating effects in both unipolar and bipolar depressed patients.
      OBJECTIVE: We aimed to assess the antidepressant augmentation effects at 48 h of
      LFMS administered on two consecutive days compared to sham treatment in treatment
      resistant depression (TRD) subjects, using the Sequential Parallel Comparison
      Design (SPCD). METHODS: Eighty-four eligible subjects with TRD were randomly
      assigned to double-blind treatment with LFMS 20 min/day for four days, sham
      treatment 20 min/day for four days, or sham treatment 20 min/day for 2 days
      followed by LFMS treatment 20 min/day for two days, using the pre-randomization
      version of the SPCD (randomization 1:1:1). The SPCD analyses used a repeated
      measures linear modeling approach with maximum likelihood estimation to use all
      available data, and using a 60-40 weighting of Stage 1 vs. 2 responses, with the
      primary outcome being measured after 2 and 4 days. RESULTS: Both primary and
      secondary outcome measures consistently showed no differences between LFMS
      treated patients and those treated with sham, with the exception of a slight, non
      significantly greater improvement than sham in the visual analogue scale (VAS)
      sad mood on LFMS-treated patients. LFMS treatment was relatively well tolerated.
      CONCLUSIONS: We did not observe a significantly greater, rapid efficacy of LFMS
      compared to sham therapy. Future studies need to examine the possible therapeutic
      effects of more intensive forms of LFMS, as other forms of neurostimulation
      typically require longer duration of exposure.

PMID- 29030114
TI  - Impairment of energy sensors, SIRT1 and AMPK, in lipid induced inflamed adipocyte
      is regulated by Fetuin A.
AB  - Although several reports demonstrated that accumulation of excess lipid in
      adipose tissue produces defects in adipocyte which leads to the disruption of
      energy homeostasis causing severe metabolic problems, underlying mechanism of
      this event remains yet unclear. Here we demonstrate that FetuinA (FetA) plays a
      critical role in the impairment of two metabolic sensors, SIRT1 and AMPK, in
      inflamed adipocytes of high fat diet (HFD) mice. A linear increase in adipocyte
      hypertrophy from 10 to 16 week was in tandem with the increase in FetA and that
      coincided with SIRT1 cleavage and decrease in pAMPK which adversely affects
      PGC1alpha activation. Knock down (KD) of FetA gene in HFD mice could
      significantly improve this situation indicating FetA's contribution in the damage
      of energy sensors in inflamed adipocyte. However, FetA effect was not direct, it
      was mediated through TNF-alpha which again is dependent on FetA as FetA augments
      TNF-alpha expression. FetA being an upstream regulator of TNF-alpha, its
      suppression prevented TNF-alpha mediated Caspase-1 activation and cleavage of
      SIRT1. FetA induced inactivation of PGC1alpha due to SIRT1 cleavage decreased
      PPARUpsilon, adiponectin, NRF1 and Tfam expression. All these together caused a
      significant fall in mitochondrial biogenesis and bioenergetics that disrupted
      energy homeostasis resulting loss of insulin sensitivity. Taken together, our
      findings revealed a new dimension of FetA, it not only induced inflammation in
      adipocyte but also acts as an upstream regulator of SIRT1 cleavage and AMPK
      activation. Intervention of FetA may be worthwhile to prevent metabolic imbalance
      that causes insulin resistance and type 2 diabetes.

PMID- 29030113
TI  - Proteomic analyses of signalling complexes associated with receptor tyrosine
      kinase identify novel members of fibroblast growth factor receptor 3 interactome.
AB  - Receptor tyrosine kinases (RTKs) form multiprotein complexes that initiate and
      propagate intracellular signals and determine the RTK-specific signalling
      patterns. Unravelling the full complexity of protein interactions within the RTK
      associated complexes is essential for understanding of RTK functions, yet it
      remains an understudied area of cell biology. We describe a comprehensive
      approach to characterize RTK interactome. A single tag immunoprecipitation and
      phosphotyrosine protein isolation followed by mass-spectrometry was used to
      identify proteins interacting with fibroblast growth factor receptor 3 (FGFR3). A
      total of 32 experiments were carried out in two different cell types and
      identified 66 proteins out of which only 20 (30.3%) proteins were already known
      FGFR interactors. Using co-immunoprecipitations, we validated FGFR3 interaction
      with adapter protein STAM1, transcriptional regulator SHOX2, translation
      elongation factor eEF1A1, serine/threonine kinases ICK, MAK and CCRK, and
      inositol phosphatase SHIP2. We show that unappreciated signalling mediators exist
      for well-studied RTKs, such as FGFR3, and may be identified via proteomic
      approaches described here. These approaches are easily adaptable to other RTKs,
      enabling identification of novel signalling mediators for majority of the known
      human RTKs.

PMID- 29030116
TI  - Population genetic data for 21 autosomal STR loci for the Saudi Arabian
      population using the GlobalFiler(r) PCR amplification kit.

PMID- 29030117
TI  - Biohydrogen production from hyperthermophilic anaerobic digestion of fruit and
      vegetable wastes in seawater: Simplification of the culture medium of Thermotoga
      maritima.
AB  - Biohydrogen production by the hyperthermophilic and halophilic bacterium T.
      maritima, using fruit and vegetable wastes as the carbon and energy sources was
      studied. Batch fermentation cultures showed that the use of a culture medium
      containing natural seawater and fruit and vegetable wastes can replace certain
      components (CaCl2, MgCl2, Balch's oligo-elements, yeast extract, KH2PO4 and
      K2HPO4) present in basal medium. However, a source of nitrogen and sulfur
      remained necessary for biohydrogen production. When fruit and vegetable waste
      collected from a wholesale market landfill was used, no decreases in total H2
      production (139 mmol L-1) or H2 yield (3.46 mol mol-1) was observed.

PMID- 29030115
TI  - Store-Operated Ca2+ Entry Controls Clonal Expansion of T Cells through Metabolic
      Reprogramming.
AB  - Store-operated Ca2+ entry (SOCE) is the main Ca2+ influx pathway in lymphocytes
      and is essential for T cell function and adaptive immunity. SOCE is mediated by
      Ca2+ release-activated Ca2+ (CRAC) channels that are activated by stromal
      interaction molecule (STIM) 1 and STIM2. SOCE regulates many Ca2+-dependent
      signaling molecules, including calcineurin, and inhibition of SOCE or calcineurin
      impairs antigen-dependent T cell proliferation. We here report that SOCE and
      calcineurin regulate cell cycle entry of quiescent T cells by controlling
      glycolysis and oxidative phosphorylation. SOCE directs the metabolic
      reprogramming of naive T cells by regulating the expression of glucose
      transporters, glycolytic enzymes, and metabolic regulators through the activation
      of nuclear factor of activated T cells (NFAT) and the PI3K-AKT kinase-mTOR
      nutrient-sensing pathway. We propose that SOCE controls a critical "metabolic
      checkpoint" at which T cells assess adequate nutrient supply to support clonal
      expansion and adaptive immune responses.

PMID- 29030118
TI  - Seed germination test for toxicity evaluation of compost: Its roles, problems and
      prospects.
AB  - Compost is commonly used for the growth of plants and the remediation of
      environmental pollution. It is important to evaluate the quality of compost and
      seed germination test is a powerful tool to examine the toxicity of compost,
      which is the most important aspect of the quality. Now the test is widely
      adopted, but the main problem is that the test results vary with different
      methods and seed species, which limits the development and application of it. The
      standardization of methods and the modelization of seeds can contribute to
      solving the problem. Additionally, according to the probabilistic theory of seed
      germination, the error caused by the analysis and judgment methods of the test
      results can be reduced. Here, we reviewed the roles, problems and prospects of
      the seed germination test in the studies of compost.

PMID- 29030119
TI  - WEEE plastic sorting for bromine essential to enforce EU regulation.
AB  - The plastics of waste of electric and electronic equipment (WEEE) are improved
      for fire safety by flame retardants, and particularly brominated flame retardants
      (BFR). As waste, the management of these plastic fractions must comply with the
      update of the regulation of waste hazard classification (2014, 2017), the
      publication of a technical standard on management of WEEE (2015), and a
      restriction of use for decabromodiphenylether in the product regulation (2017).
      Data of bromine (n=4283) and BFR concentrations (n=98) in plastics from electric
      and electronic equipment (EEE), and from WEEE processing facilities before and
      after sorting for bromine in four sites in France have been studied for chemical
      composition and for regulatory classification. The WEEE was analysed by handheld
      X-ray fluorescence, and the waste was sorted after shredding, by on-line X-ray
      transmission for total bromine content (< or > 2000 mg/kg) in small household
      appliances (SHA), cathode ray tubes (CRT) and flat screens plastics. In equipment
      (n=347), 15% of the equipment items have no bromine, while 46% have at least one
      part with bromine, and 39% have all parts brominated. The bromine concentration
      in plastics is very heterogeneous, found in high concentrations in large
      household appliance (LHA) plastics, and also found in unexpected product
      categories, as observed by other authors. Clearly, an unwanted global loop of
      brominated substances occurs via the international recycling of plastic scrap. In
      waste (n=65), polybromobiphenyls, polybromodiphenylethers (PBDE),
      tetrabromobisphenol A (TBBPA) and hexabromocyclododecane were analysed. The most
      concentrated BFRs are decaBDE (3000 mg/kg) and TBBPA (8000 mg/kg). The bromine
      concentration of regulated brominated substances was identified in 2014 and 2015
      to be up to 86% of total bromine in "old" waste (SHA, CRT), 30-50% in "younger"
      waste (Flat screens), and a mean of only 8% in recent products (2009-2013).
      Regulated substances are a minority of all the brominated substances and the only
      practical way to sort is to measure total bromine on-line. The sorting reduces
      the mean bromine concentration in the "Low Br" fraction in all sites, and reduces
      the decaBDE concentration to levels below the restricted use limit. After
      sorting, the concentration in the "High Br" fractions exceeds all present or
      future regulatory limits. In conclusion, sorting of small household appliances,
      cathode ray tubes and flat screen plastics is necessary to avoid uncontrolled
      dispersion of regulated substances in recycled raw material. Other categories
      (large household appliances, electric and electronic tools, lighting equipment)
      should also be considered, since their total bromine content (unweighted mean
      concentration) is high for some of these products. A European campaign consisting
      of 7 countries and 35 sites will begin in 2017, directed by WEEE Forum, the
      European association speaking for thirty-one not-for-profit e-waste producer
      responsibility organisations, to assess the mean bromine content of plastics from
      large household appliances after shredding.

PMID- 29030120
TI  - Hydrometallurgical recycling of lithium-ion batteries by reductive leaching with
      sodium metabisulphite.
AB  - The hydrometallurgical extraction of metals from spent lithium-ion batteries
      (LIBs) was investigated. LIBs were first dismantled and a fraction rich in the
      active material was obtained by physical separation, containing 95% of the
      initial electrode, 2% of the initial steel and 22% of plastic materials. Several
      reducers were tested to improve metals dissolution in the leaching step using
      sulphuric acid. Sodium metabisulphite led to the best results and was studied in
      more detail. The best concentration of Na2S2O5 was 0.1 M. The metals dissolution
      increased with acid concentration, however, concentrations higher than 1.25 M are
      unnecessary. Best results were reached using a stirring speed of 400 min-1. The
      metals leaching efficiency from the active material (Li, Mn, Ni, Co) increased
      with the temperature and was above 80% for temperatures higher than 60  degrees
      C. The dissolution of metals also rose with the increase in the liquid/solid
      ratio (L/S), however, extractions above 85% can be reached at L/S as lower as 4.5
      L/kg, which is favourable for further purification and recovery operations. About
      90% of metals extraction can be achieved after only 0.5 h of leaching. Sodium
      metabisulphite can be an alternative reducer to increase the leaching of Li, Mn,
      Co, and Ni from spent LIBs.

PMID- 29030121
TI  - Estimation of optimal biomass fraction measuring cycle formunicipal solid waste
      incineration facilities in Korea.
AB  - This study estimates the optimum sampling cycle using a statistical method for
      biomass fraction. More than ten samples were collected from each of the three
      municipal solid waste (MSW) facilities between June 2013 and March 2015 and the
      biomass fraction was analyzed. The analysis data were grouped into monthly,
      quarterly, semi-annual, and annual intervals and the optimum sampling cycle for
      the detection of the biomass fraction was estimated. Biomass fraction data did
      not show a normal distribution. Therefore, the non-parametric Kruskal-Wallis test
      was applied to compare the average values for each sample group. The Kruskal
      Wallis test results showed that the average monthly, quarterly, semi-annual, and
      annual values for all three MSW incineration facilities were equal. Therefore,
      the biomass fraction at the MSW incineration facilities should be calculated on a
      yearly cycle which is the longest period of the temporal cycles tested.

PMID- 29030122
TI  - A novel approach for recovery of metals from waste printed circuit boards and
      simultaneous removal of iron from steel pickling waste liquor by two-step
      hydrometallurgical method.
AB  - Waste printed circuit boards (WPCBs) and steel pickling waste liquor (SPWL) have
      received extensive attention in recent years because of its harmfulness and
      resource. In this work, two-step leaching process was carried out by using SPWL
      as the leaching agent. A series of continuously domesticated bacteria were used
      for bioleaching and the bacterial strain was identified as Acidithiobacillus
      ferrooxidans (A. ferrooxidans) by 16S rDNA gene sequence analysis. The vast
      majority of the metals in WPCBs were recovered by two-step leaching, such as Cu,
      Pb, Zn, Sn, Al, Ni. Meanwhile, a large amount of iron was removed from SPWL,
      which greatly reduces the burden of the subsequent treatment. Pulp density and pH
      were optimized to achieve maximum recovery of copper and simultaneous removal of
      iron in bioleaching. It was found that the optimum conditions were pulp density
      60 g/L and pH 0.5-1.0. Nearly 100% of copper was recovered and 51.94% of iron was
      removed under optimum conditions. The kinetic experiments showed that the rate of
      copper leaching was controlled by external diffusion rather than internal
      diffusion, because the acidic environment of the leachate prevented the formation
      of the precipitate and maintained it in a smaller size.

PMID- 29030123
TI  - Results and complications of superficialis-to-profundus tendon transfer in brain
      damaged patients, a series of 26 patients.
AB  - INTRODUCTION: In hemiplegic patients with a spastic clenched fist deformity, one
      of the goals of surgery is to address the hygiene, nursing and appearance
      problems. Transfer of the flexor digitorum superficialis (FDS) to the flexor
      digitorum profundus (FDP), initially described by Braun and colleagues, opens the
      non-functional hand in these patients. The primary objective of our study was to
      confirm the effectiveness of this technique for correcting these deformities. The
      secondary objectives were to demonstrate potential functional gains and to
      identify potential complications. MATERIAL AND METHODS: A Braun procedure was
      performed in 26 patients (9 women, 17 men, ranging in age from 36 to 79 years).
      The overall appearance of the hand was graded using the Keenan classification
      system. Complications related to the surgery were documented. The hand's function
      was evaluated with the House score. RESULTS: The average follow-up was 47 months.
      Preoperatively, all patients had a class V hand: severe clenched-fist deformity
      with zero pulp-to-palm distance. Postoperatively, 10 patients had a type I hand
      (open hand, with less than 20 degrees  spontaneous extension deficit of the
      metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints) and 12
      patients had a type II hand (20 degrees  to 40 degrees  spontaneous extension
      deficit of the MCP and PIP joints). The mean House score for all patients went
      from 0 to 0.88, and seven patients had functional improvements. Four patients had
      a forearm supination posture, 10 had intrinsic deformity with spontaneous MCP
      flexion and 6 had a swan-neck deformity. CONCLUSION: Superficialis-to-profundus
      tendon transfer (STP) provides satisfactory outcomes in terms of hand opening,
      with some patients also experiencing improved hand function. However, the
      complications cannot be ignored. LEVEL OF EVIDENCE: IV-retrospective or
      historical series.

PMID- 29030124
TI  - Targeting nitric oxide and NMDA receptor-associated pathways in treatment of high
      grade glial tumors. Hypotheses for nitro-memantine and nitrones.
AB  - Glioblastoma multiforme (GBM) is a devastating brain cancer with no curative
      treatment. Targeting Nitric Oxide (NO) and glutamatergic pathways may help as
      adjunctive treatments in GBM. NO at low doses promotes tumorigenesis, while at
      higher levels (above 300 nM) triggers apoptosis. Gliomas actively secrete high
      amounts of glutamate which activates EGR signaling and mediates degradation of
      peritumoral tissues via excitotoxic injury. Memantine inhibits NMDA-subtype of
      glutamate receptors (NMDARs) and induces autophagic death of glioma cells in
      vitro and blocks glioma growth in vivo. Nitro-memantines may exert further
      benefits by limiting NMDAR signaling and by delivery of NO to the areas of
      excessive NMDAR activity leading NO-accumulation at tumoricidal levels within
      gliomas. Due to the duality of NO in tumorigenesis, agents which attenuate NO
      levels may also act beneficial in treatment of GBM. Nitrone compounds including N
      tert-Butyl-alpha-phenylnitrone (PBN) and its disulfonyl-phenyl derivative, OKN
      007 suppress free radical formation in experimental cerebral ischemia. OKN-007
      failed to show clinical efficacy in stroke, but trials demonstrated its high
      biosafety in humans including elderly subjects. PBN inhibits the signaling
      pathways of NF-kappaB, inducible nitric oxide synthase (iNOS) and cyclooxygenase
      (COX). In animal models of liver cancer and glioblastoma, OKN-007 seemed more
      efficient than PBN in suppression of cell proliferation, microvascular density
      and in induction of apoptosis. OKN-007 also inhibits SULF2 enzyme, which promotes
      tumor growth via versatile pathways. We assume that nitromemantines may be more
      beneficial concomitant with chemo-radiotherapy while nitrones alone may act
      useful in suppressing basal tumor growth and angiogenesis.

PMID- 29030125
TI  - Prolactin gene expression in the pituitary of rats subjected to vaginocervical
      stimulation requires Erk-1/2 signaling.
AB  - Vaginocervical stimulation (VCS) induces twice-daily prolactin (PRL) surges
      resulting in pseudopregnancy in the rat. Furthermore, activation of the
      extracellular signal-regulated kinase-1/2 (Erk-1/2) is involved in the effect of
      estradiol (E2) on the Prl gene expression in pituitary cells. Herein, we
      investigated whether Erk-1/2 signaling is involved in the control of Prl
      expression in the pituitary of VCS rats and whether VCS regulates the effect of
      E2 on Erk-1/2 and Prl in the pituitary. Estrous rats were assigned as control or
      VCS groups and 0, 6, 12 or 24h later the levels and localization of
      phosphorylated Erk-1/2 (p-Erk-1/2) were analyzed in the pituitary. The effect of
      an Erk-1/2 inhibitor PD98059 on the Prl level in the pituitary of control or VCS
      rats was also analyzed. Other control or VCS rats were treated with E2 and the
      level of p-Erk-1/2 and Prl were measured in the pituitary. In control rats, p-Erk
      1/2 decreased at 6 and 12h and increased at 24h while Erk-1/2 was phosphorylated
      at all time points in VCS rats. p-Erk-1/2 was localized only in the anterior
      pituitary. PD98059 decreased Prl level in VCS, but not in control rats. Estradiol
      decreased Erk-1/2 phosphorylation although did not change Prl level in the
      pituitary of control or VCS rats. These findings show that prolonged activation
      of Erk-1/2 is necessary to induce Prl expression in the pituitary of VCS rats;
      however, VCS does not influence the role of E2 on the activation of Erk-1/2 and
      Prl expression the pituitary.

PMID- 29030126
TI  - The pesticide Lindane induces dose-dependent damage to granulosa cells in an in
      vitro culture.
AB  - Lindane, which is one of the most persistent organochlorine pesticide
      contaminating the Aral Sea region, is associated with numerous pathologies of the
      female reproductive system, including infertility, due to its gap junction
      blocker activity. By using an in vitro model of reproductive toxicity consisting
      of mouse parietal granulosa cells (GCs) exposed to increasing concentrations of
      Lindane ranging from 1 to 100MUM (L1; L10; L100), we aimed to ascertain the
      Lindane toxicity by evaluating the ultrastructure and expression of the cell
      death protein p53. GCs exposed to L1 showed an early sign of degeneration as
      chromatin marginalization and initial reduction of cell-to-cell contacts. Such
      effects increased at L10 with nuclear membrane invagination, cytoplasmic
      blebbing, reduction of microvilli and intercellular connections. L100 induced
      evident cellular damages with an extensive presence of vacuoles, cytoplasmic
      fragments, nuclear membrane vesiculation and abundant cellular debris. A dose
      dependent increase of p53 expression was evident in the L1 and L10 groups but not
      in L100. These data provide evidence for a dose-dependent reproductive toxicity
      of the gap junction blocker Lindane, as seen in mouse GCs cultured in vitro by
      ultrastructural damage compatible with apoptosis. Since gap junctions may play a
      critical role in FSH-stimulated progesterone production, the ultrastructural
      damage here evidenced could explain the increase in the prevalence of
      reproductive pathologies and infertility in exposed women. Finally, this study
      provided a useful and repeatable model of reproductive toxicity in vitro, which
      is applicable to evaluate the detrimental effects of toxicants or the reversing
      effect of protective substances.

PMID- 29030127
TI  - A method for the isolation and enrichment of purified bovine milk exosomes.
AB  - Exosomes are nanovesicles that play important roles in intercellular
      communication as they carry information to target cells. Isolation of high purity
      exosomes will aid in studying the exosomal cargo and quantity as well as how cell
      specific messages are carried. We describe a new method incorporating size
      exclusion chromatography (SEC) to enrich milk-derived exosomes from extracellular
      vesicles (EVs). This involved the initial isolation of EVs from bovine milk via
      milk processing and ultracentrifugation; followed by a new method to enrich
      exosomes using SEC. This method was compared to buoyant density gradient
      centrifugation, a widely used method of enrichment. Exosomes were characterised
      by particle concentration and size (nanoparticle tracking analysis, NTA),
      morphology (transmission electron microscopy, TEM), presence of exosomal markers
      (immunoblotting) and protein concentration (bicinchoninic acid assay, BCA).
      Proteomic profiles of exosomal fractions were analyzed by mass spectrometry using
      Information Dependant Acquisition. Milk exosomal fractions were shown to contain
      exosomal markers flotillin-1 (FLOT-1) and tumor susceptibility gene-101 (TSG
      101). The new method produced a higher yield of exosomes compared to buoyant
      density gradient centrifugation. Pooled exosomal fractions exhibited intact
      morphology by TEM. The use of SEC confirmed the fractionation of exosomes based
      on size while minimizing the interference with proteins. Tetraspanins CD9 and
      CD81 were observed via mass spectrometry in exosomal fractions. This new and
      efficient method confirmed the signatures for exosomes derived from unpasteurized
      bovine milk. Purification of exosomes is a foundational technique in the study of
      biomarkers for pathological conditions and effective drug delivery systems.

PMID- 29030129
TI  - Laryngeal and vocal alterations after thyroidectomy.
AB  - INTRODUCTION: Dysphonia is a common symptom after thyroidectomy. OBJECTIVE: To
      analyze the vocal symptoms, auditory-perceptual and acoustic vocal,
      videolaryngoscopy, the surgical procedures and histopathological findings in
      patients undergoing thyroidectomy. METHODS: Prospective study. Patients submitted
      to thyroidectomy were evaluated as follows: anamnesis, laryngoscopy, and acoustic
      vocal assessments. Moments: pre-operative, 1st post (15 days), 2nd post (1
      month), 3rd post (3 months), and 4th post (6 months). RESULTS: Among the 151
      patients (130 women; 21 men). Type of surgery: lobectomy+isthmectomy n=40, total
      thyroidectomy n=88, thyroidectomy+lymph node dissection n=23. Vocal symptoms were
      reported by 42 patients in the 1st post (27.8%) decreasing to 7.2% after 6
      months. In the acoustic analysis, f0 and APQ were decreased in women.
      Videolaryngoscopies showed that 144 patients (95.3%) had normal exams in the
      preoperative moment. Vocal fold palsies were diagnosed in 34 paralyzes at the 1st
      post, 32 recurrent laryngeal nerve (lobectomy+isthmectomy n=6; total
      thyroidectomy n=17; thyroidectomy+lymph node dissection n=9) and 2 superior
      laryngeal nerve (lobectomy+isthmectomy n=1; Total thyroidectomy+lymph node
      dissection n=1). After 6 months, 10 patients persisted with paralysis of the
      recurrent laryngeal nerve (6.6%). Histopathology and correlation with vocal fold
      palsy: colloid nodular goiter (n=76; palsy n=13), thyroiditis (n=8; palsy n=0),
      and carcinoma (n=67; palsy n=21). CONCLUSION: Vocal symptoms, reported by 27.8%
      of the patients on the 1st post decreased to 7% in 6 months. In the acoustic
      analysis, f0 and APQ were decreased. Transient paralysis of the vocal folds
      secondary to recurrent and superior laryngeal nerve injury occurred in,
      respectively, 21% and 1.3% of the patients, decreasing to 6.6% and 0% after 6
      months.

PMID- 29030128
TI  - EXPANSION of diabetes education in a United States-Mexico border community
      (Expanding Services for Patients to Acquire New Skills, Set Goals, and Improve
      Overall Knowledge).
AB  - OBJECTIVES: To describe the process used by a pharmacy team at a community health
      center to coordinate and expand diabetes education services (English and Spanish)
      for a predominantly Hispanic, Spanish-speaking population. SETTING: The project
      was implemented at 2 clinics in a federally qualified community health center
      system based in a low-income southwest U.S.-Mexico border community. PRACTICE
      INNOVATION: This project enhanced accessibility to diabetes education to improve
      knowledge, skills, and goal setting through existing pharmacy services at the
      primary clinic and 1 rural satellite clinic. EVALUATION: The success of the
      project was evaluated quantitatively. Metrics used to evaluate enhancement of
      existing practices included enrollment and completion rates, number of sessions,
      and diabetes leadership meetings. RESULTS: Over the 5-month project period
      assessed, 7 interdisciplinary professionals were certified as Diabetes
      Empowerment Education Program educators. Four sessions were conducted at both
      clinics. A total of 31 participants completed the diabetes classes. An
      educational attainment of 8th grade or less was reported in 91% of the rural
      participants compared with 50% of the urban participants. Ten interdisciplinary
      leadership meetings centered on recruitment, progress toward goals, and action
      items to ensure quality of classes. A nurse practitioner and pharmacist piloted a
      shared-visit model with 5 patients during a 45-minute time period. CONCLUSION:
      Successful diabetes education services occurred by implementing an evidence-based
      curriculum, identifying provider champions, increasing patient enrollment through
      provider referrals, and generating reports. Patient accountability was
      facilitated by setting patient-centered goals for knowledge and skills. Last,
      support groups provided ongoing support once patients graduated from a structured
      diabetes program.

PMID- 29030130
TI  - Behavioural and objective vestibular assessment in persons with osteoporosis and
      osteopenia: a preliminary investigation.
AB  - INTRODUCTION: Calcium is vital for the functioning of the inner ear hair cells as
      well as for the neurotransmitter release that triggers the generation of a nerve
      impulse. A reduction in calcium level could therefore impair the peripheric
      vestibular functioning. However, the outcome of balance assessment has rarely
      been explored in cases with osteopenia and osteoporosis, the medical conditions
      associated with reduction in calcium levels. OBJECTIVE: The present study aimed
      to investigate the impact of osteopenia and osteoporosis on the outcomes of
      behavioural and objective vestibular assessment tests. METHODS: The study
      included 12 individuals each in the healthy control group and osteopenia group,
      and 11 individuals were included in the osteoporosis group. The groups were
      divided based on the findings of bone mineral density. All the participants
      underwent behavioural tests (Fukuda stepping, tandem gait and subjective visual
      vertical) and objective assessment using cervical and ocular vestibular evoked
      myogenic potentials. RESULTS: A significantly higher proportion of the
      individuals in the two clinical groups' demonstrated abnormal results on the
      behavioural balance assessment tests (p<0.05) than the control group. However,
      there was no significant difference in latencies or amplitude of cervical
      vestibular evoked myogenic potential and oVEMP between the groups. The proportion
      of individuals with absence of ocular vestibular evoked myogenic potential was
      significantly higher in the osteoporosis group than the other two groups
      (p<0.05). CONCLUSION: The findings of the present study confirm the presence of
      balance-related deficits in individuals with osteopenia and osteoporosis. Hence
      the clinical evaluations should include balance assessment as a mandatory aspect
      of the overall audiological assessment of individuals with osteopenia and
      osteoporosis.

PMID- 29030131
TI  - Effects of diabetes mellitus and systemic arterial hypertension on elderly
      patients' hearing.
AB  - INTRODUCTION: Chronic diseases can act as an accelerating factor in the auditory
      system degeneration. Studies on the association between presbycusis and diabetes
      mellitus and systemic arterial hypertension have shown controversial conclusions.
      OBJECTIVE: To compare the initial audiometry (A1) with a subsequent audiometry
      (A2) performed after a 3 to 4-year interval in a population of elderly patients
      with diabetes mellitus and/or systemic arterial hypertension, to verify whether
      hearing loss in these groups is more accelerated when compared to controls
      without these clinical conditions. METHODS: 100 elderly individuals participated
      in this study. For the auditory threshold assessment, a previous complete
      audiological evaluation (A1) and a new audiological evaluation (A2) performed 3-4
      years after the first one was utilized. The participants were divided into four
      groups: 20 individuals in the diabetes mellitus group, 20 individuals in the
      systemic arterial hypertension group, 20 individuals in the diabetes
      mellitus/systemic arterial hypertension group and 40 individuals in the control
      group, matching them with each study group, according to age and gender. ANOVA
      and Kruskal-Wallis statistical tests were used, with a significance level set at
      0.05. RESULTS: When comparing the mean annual increase in the auditory thresholds
      of the A1 with the A2 assessment, considering each study group and its respective
      control, it can be observed that there was no statistically significant
      difference for any of the frequencies for the diabetes mellitus group; for the
      systemic arterial hypertension group, significant differences were observed after
      4kHz. For the diabetes mellitus and systemic arterial hypertension group,
      significant differences were observed at the frequencies of 500, 2kHz, 3kHz and
      8kHz. CONCLUSION: It was observed that the systemic arterial hypertension group
      showed the greatest decrease in auditory thresholds in the studied segment when
      compared to the other groups, suggesting that among the three studied conditions,
      hypertension seems to have the greatest influence on hearing.

PMID- 29030132
TI  - Improved strategies for electrochemical 1,4-NAD(P)H2 regeneration: A new era of
      bioreactors for industrial biocatalysis.
AB  - Industrial enzymatic reactions requiring 1,4-NAD(P)H2 to perform redox
      transformations often require convoluted coupled enzyme regeneration systems to
      regenerate 1,4-NAD(P)H2 from NAD(P) and recycle the cofactor for as many
      turnovers as possible. Renewed interest in recycling the cofactor via
      electrochemical means is motivated by the low cost of performing electrochemical
      reactions, easy monitoring of the reaction progress, and straightforward product
      recovery. However, electrochemical cofactor regeneration methods invariably
      produce adventitious reduced cofactor side products which result in unproductive
      loss of input NAD(P). We review various literature strategies for mitigating
      adventitious product formation by electrochemical cofactor regeneration systems,
      and offer insight as to how a successful electrochemical bioreactor system could
      be constructed to engineer efficient 1,4-NAD(P)H2-dependent enzyme reactions of
      interest to the industrial biocatalysis community.

PMID- 29030133
TI  - Use of a national database as a tool to identify primary medication non
      adherence: The Estonian ePrescription system.
AB  - BACKGROUND: Medication adherence can be divided into primary and secondary
      adherence. Primary medication non-adherence (PMN) occurs when a patient does not
      obtain medicine with their initial prescription. Secondary non-adherence measures
      prescription refills among patients who previously filled their first
      prescription. While secondary non-adherence has been studied thoroughly, PMN has
      been assessed less extensively, due to lack of available data. Estonian
      ePrescription system might prove a valuable tool for this. OBJECTIVES: The aim of
      this study was to evaluate PMN and the interval between prescribing and
      dispensing of medicines using the Estonian ePrescriptions database to establish
      its potential use for this purpose and for other qualitative drug utilization
      research measures. Osteoporosis medicines were used as an example. METHODS: The
      Estonian Prescription Centre was used to evaluate if patients purchase medicines
      after initial prescription of osteoporosis medicine. Prescriptions from 2012 to
      2015 of all patients over 18 were included. PMN was defined as the first
      prescription not being dispensed before it expired (60 days). The rate of PMN was
      calculated. RESULTS: Estonian ePrescription System enabled fast evaluation of PMN
      of osteoporosis patients based on data about prescribing, dispensing and time
      intervals in-between. Of patients who started osteoporosis treatment 13.1% were
      primary non-adherent. Of primary non-adherent patients 42% still started
      treatment at some point during the study. Of patients who did purchase their
      first prescription 80.4% did so within a week and 95% within 25 days. CONCLUSION:
      The Estonian ePrescription system is a useful tool for monitoring PMN. The PMN of
      osteoporosis medicines was identified as lower than previously reported. More
      similar type of studies about other groups of medicines would be needed to
      understand the pattern of PMN and give valuable information to healthcare
      specialists about how to increase initiation of treatment.

PMID- 29030134
TI  - A1AT polymorphisms may be associated with clinical characteristics of retrovirus
      infections in a mixed ethnic population from the Brazilian Amazon region.
AB  - OBJECTIVES: This study investigated the association of alpha-1-antrypsin
      deficiency (A1AT; S and Z polymorphisms) with HIV-1 and HTLV-1 infection.
      METHODS: Blood samples from 201 HIV-1-infected and 115 HTLV-1-infected
      individuals were examined and compared with those from 300 healthy controls.
      Genotyping of A1AT (S and Z) and quantification of plasma viral load were
      performed using RT-PCR, and the CD4+/CD8+ T-cell count was determined by flow
      cytometry. RESULTS: The wild-type MM genotype showed the highest frequency in
      each of the three groups investigated. SS and ZZ homozygous genotypes (variants)
      were observed only among HTLV-1 patients and controls, respectively. Genotype MS
      was significantly less frequent in HTLV-1-positive persons than in controls.
      Statistically significant differences were observed when comparing genotype
      frequencies between symptomatic and asymptomatic HTLV-1-infected persons. The
      distribution of plasma HIV-1 viral load among individuals with different
      genotypes of A1AT polymorphism also differed significantly. CONCLUSIONS: The
      results suggest that A1AT polymorphisms may be associated with human retrovirus
      infections when dealing with an ethnically mixed population from the Amazon
      region of Brazil.

PMID- 29030135
TI  - Staphylococcus saprophyticus: Which beta-lactam?
AB  - BACKGROUND: Staphylococcus saprophyticus is resistant to the drugs most often
      used for the empirical treatment of urinary tract infections (UTI). The adequacy
      of antimicrobial treatments prescribed for UTI due to S. saprophyticus is not
      usually questioned. This study described the epidemiology of such infections and
      assessed the susceptibility of S. saprophyticus to ceftriaxone and amoxicillin
      clavulanic acid. METHODS: Methicillin-susceptible S. saprophyticus (MSSS)
      isolated from clinical samples between November 2014 and July 2016 were included.
      Clinical data were recorded. The minimum inhibitory concentrations (MICs) of
      amoxicillin-clavulanic acid and ceftriaxone were measured for these MSSS strains
      and for 17 randomly selected methicillin-susceptible Staphylococcus aureus (MSSA)
      strains. RESULTS: Of the S. saprophyticus isolates from urine, 59.5% were
      associated with a diagnosis of cystitis and 33.3% with pyelonephritis. Sixty
      percent of S. saprophyticus cystitis cases and 25% of pyelonephritis cases were
      given an inappropriate antibiotic regimen. The MICs of ceftriaxone ranged from 4
      to >32MUg/ml for MSSS, and from 1.5 to 4MUg/ml for MSSA. CONCLUSIONS: Many UTIs
      were treated with an empirical antibiotic therapy that was ineffective for S.
      saprophyticus, revealing that S. saprophyticus is an aetiology that is
      insufficiently considered in UTI. High MICs for ceftriaxone in MSSS were
      observed, which raises questions about the use of this antibiotic in UTIs due to
      S. saprophyticus.

PMID- 29030136
TI  - Implementation of a sentinel surveillance system for influenza-like illness (ILI)
      and severe acute respiratory infection (SARI) in the country of Georgia, 2015
      2016.
AB  - OBJECTIVES: Due to reports of substandard influenza preparedness, the country of
      Georgia developed two influenza surveillance systems. This paper describes these
      surveillance systems in their capacity to detect influenza. METHODS: Two
      surveillance systems for influenza operate in Georgia: an influenza-like illness
      (ILI) sentinel surveillance system for out-patient cases, based in the capital,
      Tbilisi, and a severe acute respiratory infection (SARI) sentinel surveillance
      system for in-patient cases with five sentinel sites - one in Tbilisi, and four
      in Kutaisi. Patients in these surveillance systems provide samples for laboratory
      testing, including influenza confirmation. RESULTS: From 2015-2016, 825 cases
      were surveilled in the ILI surveillance system and 1367 cases were surveilled in
      the SARI surveillance system, with 222 (26.9%) and 451 (33.0%) positive for
      influenza, respectively. Influenza positivity varied by age with adults 30-64
      years having highest proportion of influenza-positive cases at 42.2%.
      CONCLUSIONS: The sensitivity of the surveillance systems to influenza was
      relatively high compared to neighboring countries. These findings show the
      importance of influenza surveillance in the country of Georgia.

PMID- 29030137
TI  - Video Directly Observed Therapy to support adherence with treatment for
      tuberculosis in Vietnam: A prospective cohort study.
AB  - BACKGROUND: Ensuring patients fully adhere to their treatment is a major
      challenge for TB control programmes in resource-limited settings. This study was
      conducted three outpatient tuberculosis clinics in Hanoi, Vietnam. We aimed to
      evaluate the feasibility of using asynchronous Video Directly Observed Therapy
      (VDOT) to support treatment adherence among patients with bacteriologically
      confirmed pulmonary tuberculosis. METHODS: In this cohort study, consecutive
      adult patients with bacteriologically confirmed pulmonary TB were invited to
      enroll in a programme of VDOT. Patients were trained to use a smartphone to
      record themselves taking treatment for TB. Videos were uploaded to an online
      server and reviewed daily by study staff for at least two months. Adherence was
      evaluated based upon monthly pill count. RESULTS: Between November 2016 and
      January 2017, 40 of 78 eligible participants (51.3%) agreed to commence VDOT.
      Among participating patients, 27 (71.1%) of patients took all required doses. A
      median of 88.4% (interquartile range 75.8%-93.7%) of doses were correctly
      recorded and uploaded. Participants rated the VDOT interface highly, despite
      facing some initial technical difficulties. CONCLUSION: VDOT was feasible and
      resulted in high rates of treatment adherence in a resource-limited setting.

PMID- 29030138
TI  - Peculiar purulence: Hypervirulent Klebsiella pneumoniae causing pyomyositis.
AB  - This report describes the first confirmed case of isolated pyomyositis caused by
      a hypervirulent strain of Klebsiella pneumoniae. Pyomyositis is almost
      universally caused by gram-positive organisms and while the recent emergence of
      invasive disease due to hypervirulent K. pneumoniae has been well documented, the
      most common clinical manifestation reported is liver abscess. The K. pneumoniae
      isolate in our case had a hypermucousviscous phenotype as demonstrated by a
      positive string test and was confirmed to be hypervirulent with molecular
      testing. Documenting the extrahepatic manifestations of hypervirulent Klebsiella
      pneumoniae strains is important to increase clinical awareness and in guiding
      empiric antibiotic regimens.

PMID- 29030139
TI  - Reply to letter to the Editor: "Possible intermediary role of autophagy in serum
      albumin decrease-associated cardiovascular events among patients with coronary
      heart disease".

PMID- 29030140
TI  - Cangrelor compared with clopidogrel in patients with prior myocardial infarction 
      Insights from the CHAMPION trials.
AB  - BACKGROUND: Patients who have had a prior myocardial infarction (MI) are at
      increased risk for adverse outcomes after subsequent percutaneous coronary
      intervention (PCI). OBJECTIVE: The objective of this study is to examine the
      efficacy and safety of cangrelor, a potent intravenous P2Y12 inhibitor, in
      patients with prior MI. METHODS: Pooled data from the CHAMPION trials were
      examined. Prior MI was defined as a history of MI, excluding MI events at
      baseline. The primary endpoint was a composite of death, MI, ischemia-driven
      revascularization, or stent thrombosis at 48-h post-randomization. The primary
      safety endpoint was GUSTO-defined severe bleeding at 48h. RESULTS: Out of 24,691
      patients, 5699 (23%) had a prior MI. The primary endpoint was higher in patients
      with vs. without prior MI (4.9% vs. 4.0%, p=0.002). The primary endpoint was 4.2%
      with cangrelor vs. 5.7% with clopidogrel (absolute risk reduction=1.5%; OR 0.72
      [95%CI 0.57-0.92]) in patients with prior MI and 3.7% with cangrelor vs. 4.3%
      with clopidogrel (absolute risk reduction=0.6%; OR 0.85 [95%CI 0.74-0.99]) in
      patients without prior MI (P-interaction=0.25). The rate of GUSTO-defined severe
      bleeding was 0.1% with cangrelor vs. 0.1% with clopidogrel (OR 1.39 [95%CI 0.31
      6.24]) in patients with prior MI, and 0.2% with cangrelor vs. 0.2% with
      clopidogrel (OR 1.18 [95%CI 0.65-2.14]) in patients without prior MI (P
      interaction=0.84). CONCLUSION: In the CHAMPION trials, patients with prior MI had
      higher rates of ischemic outcomes within 48h after PCI. Cangrelor reduced
      ischemic events with no significant increase in GUSTO-defined severe bleeding in
      patients with or without prior MI.

PMID- 29030141
TI  - Feasibility and usefulness of three-dimensional optical coherence tomography
      guidance for optimal side branch treatment in coronary bifurcation stenting.
AB  - BACKGROUND: For the treatment of coronary bifurcation lesions, optimal guidewire
      (GW) recrossing after main vessel stenting is important for good stent apposition
      at the side branch (SB) orifice in kissing balloon inflation (KBI). METHODS: We
      analyzed 150 bifurcation lesions treated with single stenting following KBI in
      the three-dimensional optical coherence tomography (3D-OCT) bifurcation registry
      study (2015-16) and a single center experience (2012-16). OCT examination was
      performed after GW recrossing to the SB and after KBI. Patients were divided into
      two-dimensional (2D, n=78) and 3D groups (n=72) according to 2D- or 3D-OCT
      guidance. GW recrossing position, jailing configuration of the stent over the SB
      (divided into Link-connecting type: stent link connecting to the carina and Link
      free type: no stent link at the carina) and stent apposition were compared
      between the groups. RESULTS: Distal GW recrossing was achieved in 75.6% and 91.7%
      in the 2D and 3D groups, respectively (P=0.004). Compared with the 2D group, the
      incidence of incomplete stent apposition (ISA) toward the SB in the 3D group
      tended to be lower in the whole cohort (14.5+/-13.6% vs 10.0+/-9.0%, P=0.077),
      and was significantly lower in left main trunk bifurcations (18.7+/-12.8% vs
      10.3+/-8.9%, P=0.014). Independent contributors to ISA were the Link-connecting
      type (beta 0.089, P<0.001), distal GW recrossing (beta -0.078, P=0.001), and age
      (beta -0.0020, P=0.012). CONCLUSION: Optimal GW recrossing under 3D-OCT guidance
      is feasible and improves stent apposition, which may lead to a better clinical
      outcome in the treatment of bifurcation lesions.

PMID- 29030142
TI  - Possible intermediary role of autophagy in serum albumin decrease-associated
      cardiovascular events among patients with coronary heart disease.

PMID- 29030143
TI  - Impact of atrial fibrillation on outcomes with motor vehicle accidents.
AB  - BACKGROUND: We examined the effect of AF a commonly encountered arrhythmia with
      significant morbidity on mortality following a motor vehicle accident (MVA)
      related hospitalization. METHODS: The Nationwide Inpatient Sample (NIS) was
      queried to identify patients with AF (ICD-9 CM 427.31) and MVA (ICD-9 CM E810.0
      E819.9), considered separately and together, from 2003 through 2012. Baseline
      characteristics were identified and multilevel mixed model multivariate analysis
      was employed to verify the impact of AF on in-patient mortality in survivors.
      RESULTS: Of an estimated 2,978,630 MVA admissions reported, 79,687 (2.6%)
      hospitalizations also had a diagnosis of AF. The in-hospital mortality was 2.6%
      in MVA alone and 7.6% in MVA and AF. In multivariate analysis, after adjustment
      for age, gender, Charlson Comorbidity Index (CCI), the Trauma Mortality
      Prediction Model (TMPM), and hospital characteristics, AF was independently
      associated with in-hospital mortality [Odds ratio (OR) 1.52, confidence interval
      (CI) 1.41-1.69, P value<0.0001]. In patients with MVA and AF, increasing age,
      CCI, and TMPM were associated with higher mortality. Female gender is associated
      with lower mortality (OR 0.84, CI 0.81-0.88, P -0.0016). Most patients with MVA
      and AF had a CHADS2 score of 2 (34.6%). Mortality and transfusion rates were
      higher in MVA and AF patients compared to patients with MVA alone across all
      CHADS2 scores. CONCLUSION: In patients with a MVA, the presence of AF is an
      independent risk factor for in-hospital mortality.

PMID- 29030145
TI  - Introduction to the special section: Spinal Cord a model to understand CNS
      development and regeneration.

PMID- 29030144
TI  - Regulation of the membrane structure by brassinosteroids and progesterone in
      winter wheat seedlings exposed to low temperature.
AB  - Steroids constitute one of the most important groups of compounds of regulatory
      properties both in the animal and plant kingdom. In plants, steroids such as
      brassinosteroids or progesterone, by binding to protein receptors in cell
      membranes, regulate growth and initiate processes leading to increased tolerance
      to stress conditions. Due to their structural similarities to sterols, these
      steroids may also directly interact with cellular membranes. Our aim was to
      determine the changes of the structural parameters of lipid membranes under the
      influence of hydrophobic steroid compounds, i.e., 24-epibrassinolide (EBR) and
      its precursor-24-epicastasterone (ECS) and progesterone (PRO). Lipids were
      isolated from wheat seedlings with different tolerances to frost, grown at low
      temperatures (5  degrees C) for 1.5 and 3 weeks (acclimation process). Control
      plants were cultured continuously at 20  degrees C. From galactolipids and
      phospholipids, the main polar lipid fractions, the monolayers were formed, using
      a technique of Langmuir trough. EBR and ECS were introduced into monolayers,
      together with lipids, whereas the PRO was dissolved in the aqueous sub-phase upon
      which the monolayers were spread. Measurements performed at 25  degrees C and 10 
      degrees C showed a significant action of the tested compounds on the
      physicochemical properties of the monolayers. EBR and PRO increased the area per
      lipid molecule in monolayers, resulting in formation of more flexible surface
      structures while the presence of the ECS induced the opposite effect. The
      influence of the polarity of lipids and steroids on the interactions in the
      monolayer was discussed. Lipids extracted from the membranes of wheat with the
      most tolerance to frost were characterized by the highest fatty acid unsaturation
      and steroids had a relatively weak effect on the parameters of the structure of
      their monolayers.

PMID- 29030146
TI  - Salamander spinal cord regeneration: The ultimate positive control in vertebrate
      spinal cord regeneration.
AB  - Repairing injured tissues / organs is one of the major challenges for the
      maintenance of proper organ function in adulthood. In mammals, the central
      nervous system including the spinal cord, once established during embryonic
      development, has very limited capacity to regenerate. In contrast, salamanders
      such as axolotls can fully regenerate the injured spinal cord, making this a very
      powerful vertebrate model system for studying this process. Here we discuss the
      cellular and molecular requirements for spinal cord regeneration in the axolotl.
      The recent development of tools to test molecular function, including CRISPR
      mediated gene editing, has lead to the identification of key players involved in
      the cell response to injury that ultimately leads to outgrowth of neural stem
      cells that are competent to replay the process of spinal cord development to
      replace the damaged/missing tissue.

PMID- 29030147
TI  - [Report from the CFEF seminar on fetal biometry (June 2017)].
AB  - This article reports the conclusions and recommendations resulting from the
      seminar organized in Paris on June 15, 2017 by the scientific committee of the
      French College of Fetal Ultrasound (CFEF). The purpose of this meeting was to
      audit the practices in screening for SGA and IUGR fetuses in France and to
      discuss ways to improve ultrasound screening. A review of charts, references,
      standards and common practices was performed. The potential new biometric tools
      applicable in France were reviewed and analyzed. Eventually, options and
      recommendations for improvement are proposed.

PMID- 29030148
TI  - [Robot-assisted laparoscopic radical trachelectomy for early stage cervical
      cancer (with video)].

PMID- 29030149
TI  - Clinical management of women presenting with field effect of HPV and
      intraepithelial disease.
AB  - Anogenital human papillomavirus is the most common sexually transmitted infection
      acquired through skin-to-skin contact. Most infections are cleared by an intact
      immune system. Persistence of these infections results in precancerous lesions
      and, eventually, to cancers of the cervix, vagina, vulva, and perianal area. The
      introduction of the prophylactic human papilloma virus (HPV) vaccinations may
      reduce the incidence of these infections, but the effect of these vaccinations
      will be seen only in the decades that follow. In the meantime, multiple therapies
      such as immune modulators, ablative modalities, and surgical excision are used in
      an attempt to treat precancerous lesions and hence prevent cancer. There is an
      increase in multicentric disease in young women, especially with the HIV epidemic
      and in women who are immune compromised. This article aims to address the
      challenges and management options in women who have a field effect of HPV
      associated disease.

PMID- 29030150
TI  - Sociodemographic, socioeconomic, and clinical determinants of survival in
      patients with cancer: A systematic review of the literature focused on the
      elderly.
AB  - Studies on cancer survival have revealed disparities not only between the elderly
      and their younger counterparts, but also among the elderly themselves. The aim of
      this work was to identify sociodemographic, socioeconomic, clinical, and care
      related determinants of survival or mortality in older patients with cancer by a
      systematic synthesis of the literature. Understanding these factors is of great
      value for guiding health policies and programs aimed at reducing cancer survival
      disparities. We conducted a search of MEDLINE and SCOPUS databases under PRISMA
      guidelines. Results were limited to articles published in English and French from
      2005 to 2015, and focused on elderly patients with cancer. The article selection
      was performed in a stepwise fashion: title, abstract, and full-text selection.
      Studied determinants and results of each article were synthesized. Forty-five
      articles were eligible and included in the study. We observed different ways of
      measuring socioeconomic status, comorbidities, and treatment among studies.
      Cancer-specific and overall survival were the main studied outcomes. Advanced
      age, low income, low socioeconomic status, presence of comorbidities, advanced
      stage, and poor tumor grade were found to be associated with lower survival or
      higher mortality. On the other hand, female gender and being married were
      predictive of increased survival or lower mortality. The next logical step is to
      carry out studies on elderly patients from different countries and to incorporate
      pertinent factors in a unique model. Moreover, specific geriatric health
      impairments should be taken into account in further research because of their
      association with survival.

PMID- 29030151
TI  - Optimizing bicoid signal extraction.
AB  - Signal extraction and analysis is of great importance, not only in fields such as
      economics and meteorology, but also in genetics and even biomedicine. There
      exists a range of parametric and nonparametric techniques which can perform
      signal extractions. However, the aim of this paper is to define a new approach
      for optimising signal extraction from bicoid gene expression profile. Having
      studied both parametric and nonparametric signal extraction techniques, we
      identified the lack of specific criteria enabling users to select the optimal
      signal extraction parameters. Exploiting the expression profile of bicoid gene,
      which is a maternal segmentation coordinate gene found in Drosophila
      melanogaster, we introduce a new approach for optimising the signal extraction
      using a nonparametric technique. The underlying criteria are based on the
      distribution of the residual, more specifically its skewness.

PMID- 29030152
TI  - Identification of microbiota dynamics using robust parameter estimation methods.
AB  - The compositions of in-host microbial communities (microbiota) play a significant
      role in host health, and a better understanding of the microbiota's role in a
      host's transition from health to disease or vice versa could lead to novel
      medical treatments. One of the first steps toward this understanding is modeling
      interaction dynamics of the microbiota, which can be exceedingly challenging
      given the complexity of the dynamics and difficulties in collecting sufficient
      data. Methods such as principal differential analysis, dynamic flux estimation,
      and others have been developed to overcome these challenges. Despite their
      advantages, these methods are still vastly underutilized in fields such as
      mathematical biology, and one potential reason for this is their sophisticated
      implementation. While this paper focuses on applying principal differential
      analysis to microbiota data, we also provide comprehensive details regarding the
      derivation and numerics of this method and include a functional implementation
      for readers' benefit. For further validation of these methods, we demonstrate the
      feasibility of principal differential analysis using simulation studies and then
      apply the method to intestinal and vaginal microbiota data. In working with these
      data, we capture experimentally confirmed dynamics while also revealing potential
      new insights into the system dynamics.

PMID- 29030154
TI  - Simultaneous profiles of sulfonated androgens, sulfonated estrogens and
      sulfonated progestogens in postpubertal boars (sus scrofa domestica) measured by
      LC-MS/MS.
AB  - Sulfonated steroids (s-St) have been usually regarded as inactive metabolites but
      are progressively considered as precursors for the intra-tissue formation of
      bioactive steroids. Moreover, independent effects without preceding removal of
      the sulfate group have been observed. We use the porcine testicular-epididymal
      compartment as a model to investigate the still largely unknown s-St physiology
      as the boar exhibits an intriguingly broad s-St spectrum predominantly
      originating from the testis. The application of LC-MS/MS in steroidomics enables
      the determination of unconjugated and intact sulfonated steroids with currently
      highest specificity and good sensitivity, allowing the concurrent measuring of
      numerous analytes in larger quantities of samples. Profiles (6h, 20min intervals)
      were generated for sulfonated 5-androstene-3beta,17beta-diol (Adiol-S),
      androsterone (A-S), dehydroepiandrosterone (DHEA-S), epiandrosterone (EA-S),
      epitestosterone (ET-S), estrone (E1-S), estradiol-17beta (E2-S), pregnenolone (P5
      S), 17alphaOH-pregnenolone (OHP5-S) and unconjugated testosterone (T) in four
      unstimulated and four hCG-stimulated boars. Moreover, concentrations were
      measured in individual samples collected from testicular afferent and efferent
      blood to differentiate between testicular vs. extratesticular origin. Highest
      concentrations were found for EA-S, followed by ET-S, Adiol-S and DHEA-S, which
      mostly exceeded the levels of E1-S and A-S. Lowest concentrations were obtained
      for E2-S, P5-S and OHP5-S. The analytical profile also included sulfonated T,
      5alpha-dihydrotestosterone and cholesterol. However, their concentrations were
      below the limit of quantification. Profiles of quantifiable s-St were consistent
      with a wave-like pattern associated with T pulses. In postpartal females (n=5)
      concentrations of all analytes assessed were undetectable, suggesting that in
      pigs the adrenals are not a quantitatively significant source of s-St.

PMID- 29030153
TI  - Potassium homeostasis in health and disease: A scientific workshop cosponsored by
      the National Kidney Foundation and the American Society of Hypertension.
AB  - While much emphasis, and some controversy, centers on recommendations for sodium
      intake, there has been considerably less interest in recommendations for dietary
      potassium intake, in both the general population and patients with medical
      conditions, particularly acute and chronic kidney disease. Physiology literature
      and cohort studies have noted that the relative balance in sodium and potassium
      intakes is an important determinant of many of the sodium-related outcomes. A
      noteworthy characteristic of potassium in clinical medicine is the extreme
      concern shared by many practitioners when confronted by a patient with
      hyperkalemia. Fear of this often asymptomatic finding limits enthusiasm for
      recommending potassium intake and often limits the use of renin-angiotensin
      aldosterone system blockers in patients with heart failure and chronic kidney
      diseases. New agents for managing hyperkalemia may alter the long-term management
      of heart failure and the hypertension, proteinuria, and further function loss in
      chronic kidney diseases. In this jointly sponsored effort between the American
      Society of Hypertension and the National Kidney Foundation, 3 panels of
      researchers and practitioners from various disciplines discussed and summarized
      current understanding of the role of potassium in health and disease, focusing on
      cardiovascular, nutritional, and kidney considerations associated with both hypo-
      and hyperkalemia.

PMID- 29030155
TI  - High glucose impaired estrogen receptor alpha signaling via beta-catenin in
      osteoblastic MC3T3-E1.
AB  - Diabetic Mellitus is a risk factor for osteoporosis. It has been suggested that
      altered estrogen or estrogen receptor alpha/beta (ERalpha/beta) signaling may be
      involved in diabetic osteoporosis. The present study is to investigate the
      effects of high glucose on ERalpha/beta signaling in osteoblastic MC3T3-E1 and
      how the altered signaling of ERalpha/beta affect osteoblastic bone formation.
      ERalpha/beta signaling was demonstrated as ERalpha/beta protein expression
      (Western Blotting) and ER transcription activity (Luciferase Reporter assays).
      Proliferation (WSK-1 assaying), differentiation (ALP staining) and mineralization
      (Alizalard Red staining) of MC3T3-E1 were examined to evaluate bone formation
      function. It has been found that high glucose increased ERalpha/beta expression
      dose-dependently and time-dependently, but high glucose (33mM) decreased ERalpha
      transcription activity. 17beta-estradiol increased the ERalpha/beta expression
      dose-dependently in normal medium, but decreased the ERalpha/beta expression dose
      dependently in medium with high glucose (33mM). High glucose decreased bone
      formation and also decreased the osteogenic effects of 17beta-estradiol (10-8M).
      High glucose decreased beta-catenin expression dose-dependently and time
      dependently. LiCl, an inhibitor of beta-catenin degradation, decreased ERalpha
      expression but increased ERalpha transcription activity. When compared with high
      glucose treatment, LiCl (5mM) increased ALP activity and calcified nodes.
      Besides, high glucose also decreased the protein expression PI-3K, pAKT/AKT, GSK
      3beta. In conclusion, the present study suggested that high glucose may impair
      ERalpha transcription activity by inhibiting beta-catenin signaling in
      osteoblastic MC3T3-E1, leading decreased bone formation ligand-dependently or
      ligand-independently.

PMID- 29030156
TI  - Applicability of an innovative steroid-profiling method to determine synthetic
      growth promoter abuse in cattle.
AB  - A robust LC-MS/MS method was developed to quantify a large number of phase I and
      phase II steroids in urine. The decision limit is for most compounds lower than
      1ngml-1 with a measurement uncertainty smaller than 30%. The method is fully
      validated and was applied to assess the influence of administered synthetic
      steroids and beta-agonists on the steroidogenesis. From three animal experiments,
      clenbuterol, diethylstilbestrol and stanozolol, the steroid profiles in urine of
      bovine animals were compared before and after treatment. It was demonstrated that
      the steroid profiles were altered due to these treatments. A predictive
      multivariate model was built to identify deviations from normal population
      steroid profiles. The abuse of synthetic steroids can be detected in urine
      samples from bovine animals using this model. The samples from the animal
      experiments were randomly analysed using this method and predictive model. It was
      shown that these samples were predicted correctly in the exogenous steroids
      group.

PMID- 29030157
TI  - Bits and Pieces: A Crowd-Sourced Series of 54 Cases of Fractured Hormonal
      Implants.
AB  - STUDY OBJECTIVE: The fracture of hormonal implants, including Implanon, Nexplanon
      (both from Merck & Co, Inc), and histrelin acetate is rare. Our aim was to
      describe patient demographic characteristics, mechanisms, and consequences of
      fractured implants by surveying physicians' experience via listservs and social
      media. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES:
      We developed a Research Electronic Data Capture survey for physicians regarding
      their experience with implant fracture, including patient characteristics,
      mechanism of fracture, changes in menstrual bleeding patterns, time from
      insertion to fracture, and time from fracture to seeking care. We distributed the
      survey to providers in listservs for the North American Society for Pediatric and
      Adolescent Gynecology, the Family Planning Fellowship, the Ryan Program, and the
      Facebook Physician Moms Group and Facebook OB-GYN Mom Group. We performed
      descriptive analyses. RESULTS: We received 42 survey responses, representing 54
      discrete implant fractures of which 70% (n=14) were Nexplanon, 26% (n=38) were
      Implanon, and 4% (n=2) were histrelin acetate. Mechanisms of implant fracture
      included patient manipulation (23%, n=12), unintentional trauma (11%, n=6),
      interpersonal violence (8%, n=4), lifting/carrying (6%, n=3), fracture with
      removal (6%, n=3), and unknown (47%, n=25). Bleeding pattern was not altered in
      78% (n=42) of cases. Time interval between placement and fracture was less than 2
      years for 63% (n=34) of cases. Thirty-nine percent (n=21) of patients presented
      for care more than 1 month from the time of fracture. CONCLUSION: Patients should
      be counseled about potential for hormonal implant fracture, advised against
      excessive manipulation of implants, and counseled to present for care immediately
      upon noticing an implant fracture. Surveying physicians through listervs and
      social media is an effective strategy to increase the reporting of rare
      complications and events.

PMID- 29030158
TI  - Surgical Treatment of Adolescent Breast Disorders: Institutional Experience and
      National Trends.
AB  - STUDY OBJECTIVE: Adolescent breast disorders are rare and typically benign in
      nature; however, surgical treatments might require multiple surgeries. Because of
      the limited existing data, we sought to evaluate national trends and describe our
      institutional experience to help guide patient conversations. DESIGN:
      Retrospective review. SETTING: National database and academic institution.
      PARTICIPANTS: Patients 20 years old or younger who underwent a breast procedure
      in the Kids' Inpatient Database from January 2000 to December 2012 and at Mayo
      Clinic-Rochester from January 2000 to July 2016. Conditions were categorized into
      common and complex breast disorders. INTERVENTIONS: None. MAIN OUTCOME MEASURES:
      To assess any trend of adolescent breast procedures across the United States as a
      whole, weighted Kids' Inpatient Database data were assessed using a Rao-Scott
      chi2 test. Within the institutional data, the average number of procedures needed
      to correct common vs complex breast disorders were compared using an unequal
      variance t test. RESULTS: In recent years, the estimated number of
      hospitalizations for breast procedures decreased in the United States from 1661
      in 2000 to 1078 in 2012 (P < .001). At our institution, 241 patients underwent a
      breast procedure (75.1% [181/241] female) over 16 years. Common breast disorders
      were corrected with fewer procedures than complex breast disorders (mean 1.09 vs
      2.22 procedures; P = .0003). CONCLUSION: Inpatient treatment of adolescent breast
      disorders has been decreasing in recent years, likely reflecting a trend to
      outpatient procedures. Common adolescent breast disorders might be surgically
      corrected with 1 procedure, whereas complex disorders often require multiple
      surgeries to correct. It is important to discuss this with patients and their
      families to adequately set up expectations.

PMID- 29030159
TI  - Obstructive Mullerian Anomalies in Menstruating Adolescent Girls: A Report of 22
      Cases.
AB  - STUDY OBJECTIVE: To assess the clinical course of obstructive Mullerian anomalies
      found in girls after menarche. DESIGN: A retrospective case series of adolescents
      who, between 2009 and 2016, were treated for vaginal or uterine obstructive
      malformations diagnosed after menarche. SETTING: Division of Gynecology, Poznan
      University of Medical Sciences, Poznan, Poland. PARTICIPANTS AND INTERVENTIONS:
      Twenty-two patients who, at the age range between 11.4 and 18.2 (median, 13.1)
      years, between 2 and 74 (median 7.5) months after menarche, underwent surgical
      repair of obstructive genital anomaly. MAIN OUTCOME MEASURES: Mullerian defect
      type, presentation, radiologic findings, pre- and postoperative course. RESULTS:
      Eighteen patients (18 of 22; 81.8%) were diagnosed with obstructed hemivagina
      ipsilateral renal anomaly syndrome. One patient (1 of 22; 4.5%) was diagnosed
      with uterus didelphys and unilateral cervical atresia. Three patients (3 of 22;
      13.6%) had unicornuate uterus with a cavitated, noncommunicating rudimentary
      horn. The right side was affected in 13 patients (13 of 22; 59.1%), and the left
      side in 9 patients (9 of 22; 40.9%; P > .05). All but 1 patient had renal
      agenesis on the side of obstruction. Before repair of the obstructive genital
      anomaly, 4 patients underwent unnecessary surgeries for misdiagnosed ovarian
      cysts. Serious complications (pelvic inflammatory disease, vesicovaginal fistula)
      occurred in 2 patients with microperforated pyocolpos. Pelvic endometriosis was
      found in 4 of our patients. CONCLUSION: Our case series suggests that obstructed
      hemivagina ipsilateral renal anomaly syndrome is the most common obstructive
      Mullerian anomaly diagnosed in adolescents after menarche. The differential
      diagnosis for unilateral kidney agenesis accompanied by dysmenorrhea in
      adolescent girls should include obstructive genital tract anomaly. Accurate
      diagnosis of an obstructive genital anomaly early after menarche might help
      prevent unnecessary surgeries and infection-related complications. Meanwhile,
      prompt surgical correction of an obstructive genital tract anomaly results in
      relief of symptoms and might reduce the risk of endometriosis.

PMID- 29030160
TI  - Mobile Application vs Paper Pictorial Blood Assessment Chart to Track Menses in
      Young Women: A Randomized Cross-over Design.
AB  - STUDY OBJECTIVE: Heavy menstrual bleeding is a common symptom reported by
      approximately 30% of women. The Pictorial Blood Assessment Chart (PBAC) score is
      often used to quantify severity of menstrual bleeding. However, the traditional
      PBAC paper diary might be subject to recall bias and compliance issues,
      especially in adolescents. We developed a mobile application (app) version of the
      PBAC score and evaluated patient satisfaction and compliance with app reporting
      vs paper reporting. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN
      OUTCOME MEASURES: This study was a randomized cross-over study of 25
      postmenarchal female adolescents and young women ages 13-21 years. Participants
      agreed to track bleeding in 2 consecutive menstrual cycles and were randomized to
      use the PBAC paper diary or mobile app format first. At the end of each cycle, a
      satisfaction survey and system usability scale (app only) was used to assess the
      acceptability of the format used. RESULTS: Twenty-five participants had a median
      age of 15 years. Cross-over analysis showed that satisfaction level was
      significantly higher for the app (P < .001). Twenty of 25 (80%) participants
      preferred the app over the paper diary. For the app, 20 of 25 participants (80%)
      had high compliance for reporting bleeding, with a mean of 2 app entries per day.
      Participants' PBAC scores did not vary significantly between the paper diary
      (median, 95) and mobile app (median, 114). All paper diaries met definition for
      high compliance. There was no significant period or carryover effect. CONCLUSION:
      This study showed that a PBAC app compared with the paper diary was the preferred
      method of recording menstrual bleeding in adolescents and showed feasibility as a
      research data collection tool.

PMID- 29030161
TI  - ASGE EndoVators Summit: Defining the role and value of endoscopic therapies in
      obesity management.

PMID- 29030162
TI  - Commentary on EndoVators summit white paper.

PMID- 29030163
TI  - Metabolites related to renal function, immune activation, and carbamylation are
      associated with muscle composition in older adults.
AB  - Reduced skeletal muscle density in older adults is associated with insulin
      resistance, decreased physical function, and an increased all-cause mortality
      risk. To elucidate mechanisms that may underlie the maintenance of skeletal
      muscle density, we conducted a secondary analysis of previously published muscle
      composition and serum metabolomic data in 73 older adults (average age, 78y).
      Multivariable-adjusted linear regression was used to examine associations between
      321 metabolites with muscle composition, defined as the ratio between normal
      density (NDM) with low density (LDM) thigh muscle cross sectional area (NDM/LDM).
      Sixty metabolites were significantly (p<=0.05 and q<0.30) associated with
      NDM/LDM. Decreased renal function and the immune response have been previously
      linked with reduced muscle density, but the mechanisms underlying these
      connections are less clear. Metabolites that were significantly associated with
      muscle composition were then tested for their association with circulating
      markers of renal function (blood urea nitrogen, creatinine, uric acid), and with
      the immune response (neutrophils/lymphocytes) and activation
      (kynurenine/tryptophan). 43 significant NDM/LDM metabolites (including urea) were
      co-associated with at least 1 marker of renal function; 23 of these metabolites
      have been previously identified as uremic solutes. The neutrophil/lymphocyte
      ratio was significantly associated with NDM/LDM (beta+/-SE: -0.3+/-0.1, p=0.01,
      q=0.04). 35 significant NDM/LDM metabolites were co-associated with immune
      activation. Carbamylation (defined as homocitrulline/lysine) was identified as a
      pathway that may link renal function and immune activation with muscle
      composition, as 29 significant NDM/LDM metabolites were co-associated with
      homocitrulline/lysine, with at least 2 markers of renal function, and with
      kynurenine/tryptophan. When considering that elevated urea and uremic metabolites
      have been linked with an increased systemic microbial burden, that antimicrobial
      defense can be reduced in the presence of carbamylation, and that adipocytes can
      promote host defense, we propose the novel hypothesis that the age-related
      increase in adipogenesis within muscle may be a compensatory antimicrobial
      response to protect against an elevated microbial burden.

PMID- 29030164
TI  - Renal function as a cofactor for risk stratification and short-term outcome in
      acute pulmonary embolism.
AB  - BACKGROUND: In addition to right ventricular dysfunction (RVD) and myocardial
      injury, impaired renal function is connected with poorer prognosis in pulmonary
      embolism (PE). We aimed to investigate renal function as a cofactor for risk
      stratification in PE. METHODS: Data from 182 patients with PE, treated between
      May 2006 and June 2011, were analysed retrospectively. PE patients with elevated
      creatinine were compared with those with normal values. Logistic regression
      models were calculated to investigate associations between creatinine and
      myocardial necrosis, RVD and in-hospital death. Prognostic performance of
      creatinine for prediction of myocardial necrosis and RVD were computed. RESULTS:
      Overall, 182 patients (61.5% females,aged 68.5+/-15.3years) with confirmed PE
      were included in this study; 142 patients(78.0%) showed normal creatinine, and
      40(22.0%) had an elevated creatinine. Patients with elevated creatinine were
      older (75.9+/-10.7 vs. 66.5+/-15.7years, P=0.0003), more frequently female (77.5%
      vs. 57.0%,P=0.019), and had higher cardiac troponin I (0.19+/-0.23 vs. 0.11+/
      0.29ng/ml,P=0.0004), systolic pulmonary artery pressure (43.18+/-16.69 vs.
      30.83+/-17.53mmHG,P=0.0006) and percentage of RVD (77.1% vs. 54.1%,P=0.040).
      Creatinine was significantly and independently associated with myocardial
      necrosis (OR 10.192, 95%CI 2.850-36.452, P=0.0004), shock-index>=1.0 (OR 3.265,
      95%CI 1.067-9.992, P=0.0381) and RVD (OR 5.172, 95%CI 1.387-19.295, P=0.014).
      Creatinine>1.25mg/dl indicated for myocardial necrosis (AUC 0.680) and RVD (AUC
      0.663). CONCLUSIONS: Additionally, to RVD and myocardial necrosis, impaired renal
      function could give further information for risk stratification in PE. Cardio
      pulmonary-renal interactions in PE seem to be multi-factorial.

PMID- 29030165
TI  - Hippocampal mTOR signaling is required for the antidepressant effects of
      paroxetine.
AB  - Although thought as a selective serotonin reuptake inhibitor (SSRI), the
      antidepressant mechanisms of paroxetine remain unknown. Previous studies have
      shown the role of the mammalian target of rapamycin (mTOR) signaling in
      depression. In this study, we investigated whether the antidepressant effects of
      paroxetine require mTOR signaling. We first examined whether chronic paroxetine
      administration restores the effects of CUMS and CSDS on the mTOR signaling
      cascade in the hippocampus and prefrontal cortex. Then, the pharmacologcial
      inhibitors of mTOR signaling (LY294002, U0126 and rapamycin) were used to assay
      if the paroxetine-induced reversing effects in the CUMS and CSDS models were
      prevented by mTOR system blockade. Furthermore, gene knockdown of mTOR by mTOR
      shRNA was also used to test whether mTOR is necessary for the antidepressant
      effects of paroxetine. It was found that paroxetine treatment fully reversed the
      effects of CUMS and CSDS on the mTOR signaling in the hippocampus, but not the
      prefrontal cortex. Pharmacological inhibition of the mTOR signaling significantly
      blocked the antidepressant effects of paroxetine in the CUMS and CSDS models.
      Moreover, gene silencing of hippocampal mTOR by mTOR-shRNA also abolished the
      antidepressant effects of paroxetine. Taken together, hippocampal mTOR signaling
      is necessary for the antidepressant effects of paroxetine.

PMID- 29030166
TI  - MDPV and alpha-PVP use in humans: The twisted sisters.
AB  - The new psychoactive substances phenomenon continues to represent a considerable
      public health challenge. Synthetic cathinones are beta-keto amphetamine
      analogues, also known as legal highs, research chemicals, bath salts. These drugs
      have surfaced as a popular alternative to other illicit drugs of abuse, such as
      cocaine, MDMA, and methamphetamine, due to their potent psychostimulant and
      empathogenic effects. Pyrovalerone cathinones (a-pyrrolidinophenones) form a
      distinct group of designer cathinones, such as MDPV. After being listed as an
      illegal product, "second generation" compounds such as alpha-PVP, sharing a very
      similar chemical structure with MDPV, were developed. Clinical effects of these
      compounds are individual, dose- and route of administration-dependent. Both of
      them have been involved in an increased number of, not only acute intoxications
      but also fatalities over the past few years, raising concerns in the medical
      field. In this paper, we will review the available data regarding the use and
      effects of MDPV and alpha-PVP in humans in order to highlight their impact on
      public health. Health actors and general population need to be clearly informed
      of potential risks and consequences of these 2 novel psychoactive substances
      spread and use. The literature search conducted led to the identification of
      potentially 83 relevant articles. All articles were screened from their abstracts
      to determine their relevance in the framework of the current review. This article
      is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'

PMID- 29030167
TI  - Turnaround time of whole genome sequencing for mycobacterial identification and
      drug susceptibility testing in routine practice.
AB  - OBJECTIVES: Until recently whole genome sequencing (WGS) for mycobacteria has
      been restricted mostly to the research setting. However, in 2017 Public Health
      England has implemented WGS for routine mycobacterial identification and
      susceptibility testing for Mycobacterium tuberculosis. Our objective was to
      evaluate the impact of this change on the laboratory turnaround times and
      availability of results. METHODS: Over the years 2016 and 2017, the period 1
      January to 30 April was selected to represent before and after implementation of
      WGS. Prior to 2017, line probe assays were used for mycobacterial species
      identification. Turnaround times for the different steps of the diagnostic
      process were evaluated for all positive mycobacterial cultures that were sent
      from our hospital to the Reference Laboratory during the study period. RESULTS: A
      total of 161 positive mycobacterial cultures were sent to the Reference
      Laboratory. Half of the isolates (n=81/161, 50%) were M. tuberculosis and 80/161
      (50%) were non-tuberculous mycobacteria. The median number of workdays for
      mycobacterial species identification was 1 day (interquartile range (IQR) 1-3) in
      2016 and 6 days (IQR 5-7) in 2017, p <0.001. For M. tuberculosis complex, the
      median time to drug susceptibility testing results, either molecular or
      phenotypic, was 12 days (IQR 11-18) in 2016 and 8 days (IQR 7-10) in 2017, p
      <0.001. CONCLUSIONS: Routine WGS performed well in this setting for mycobacterial
      identification and susceptibility testing for M. tuberculosis and decreased time
      to drug susceptibility testing results. There was an increase in turnaround times
      for species identification using WGS, when compared with the previous methods.

PMID- 29030168
TI  - Shiga toxin-producing Escherichia coli: incidence and clinical features in a
      setting with complete screening of patients with suspected infective diarrhoea.
AB  - OBJECTIVES: Shiga toxin-producing Escherichia coli (STEC) causes diarrhoeal
      disease, bloody diarrhoea, and haemolytic uraemic syndrome. The aim of this study
      was to describe the incidence of STEC and the clinical features of STEC patients
      from a well-defined Danish population in which all fecal samples of patients with
      suspected infective gastroenteritis were analysed for STEC. METHODS: In this
      population-based cohort study, all stool samples referred to two clinical
      microbiology laboratories were screened for STEC by culture and/or PCR.
      Epidemiological (n=170) and clinical (n=209) characteristics were analysed using
      data from local and national registries. RESULTS: Overall, 75,132 samples from
      30,073 patients were screened resulting in 217 unique STEC-isolates. The
      epidemiological analysis showed an incidence of 10.1 cases per 100,000 person
      years, which was more than twofold higher than the incidence in the rest of
      Denmark (3.4 cases per 100,000 person-years, p <0.001). Three groups were
      associated with a higher incidence: age <5 years (n=28, p <0.001), age >=65 years
      (n=38, p 0.045), and foreign ethnicity (n=27, p 0.003). In the clinical analysis,
      patients with STEC harbouring only the Shiga toxin 1 gene (stx1-only isolates)
      showed a lower frequency of acute (n=11, p <0.05) and bloody diarrhoea (n=5, p
      <0.05) and a higher frequency of gastrointestinal symptoms for >=3 months (n=8, p
      <0.05) than the other STEC patients. CONCLUSIONS: We report a more than twofold
      higher incidence in the project area compared with the rest of Denmark,
      indicating that patients remain undiagnosed when selective STEC screening is
      used. We found an association between patients with stx1-only isolates and long
      term gastrointestinal symptoms.

PMID- 29030169
TI  - Clinical predictors and prediction rules to estimate initial patient risk for
      infective endocarditis in Staphylococcus aureus bacteraemia: attention must be
      paid to the reference standard.

PMID- 29030170
TI  - In utero negativization of Zika virus in a foetus with serious central nervous
      system abnormalities.
AB  - We describe a case of a pregnant woman with Zika virus (ZIKV) infection and a
      foetus with severe brain malformations. ZIKV tested positive in amniotic fluid at
      19 weeks but was negative at delivery. The newborn did not meet the case
      definition of congenital ZIKV syndrome because neither ZIKV RNA nor IgM
      antibodies were detected; however, prenatal brain lesions were confirmed after
      birth (Graphical Abstract).

PMID- 29030171
TI  - To test or not to test? Laboratory support for the diagnosis of Lyme borreliosis.

PMID- 29030172
TI  - Towards a structured examination of contextual flexibility in persistent pain.

PMID- 29030173
TI  - A novel miniature, wireless neurostimulator in the management of chronic
      craniofacial pain: Preliminary results from a prospective pilot study.
AB  - OBJECTIVE: To report a novel wireless neuromodulation system for treatment of
      refractory craniofacial pain. BACKGROUND: Previous studies utilizing peripheral
      nerve stimulation (PNS) of the occipital and trigeminal nerves reported positive
      outcomes for alleviating neuropathic pain localized to the craniofacial and
      occipital areas. However several technological limitations and cosmetic concerns
      inhibited a more widespread acceptance and use of neuromodulation. Also, a
      relatively high incidence of adverse events like electrode erosions, dislocation,
      wire fracture and/or infection at the surgical site mandates a change in our
      approach to neuromodulation technology and implant techniques in the craniofacial
      region. METHODS: We report a novel approach for the management of craniofacial
      pain with a wirelessly powered, minimally invasive PNS system. The system is
      percutaneously implanted and placed subcutaneously adjacent to affected facial
      nerves via visual guidance by the clinician. In this feasibility study, pilot
      evidence was gathered in a cohort of ten subjects suffering from a combination of
      chronic headaches, facial pain for at least 15 days per month and for at least
      4h/day. RESULTS: At four weeks post-implant follow up, all patients reported
      sustained pain relief of the primary pain area. Electrode location and total
      number of electrodes used per subject varied across the cohort. The average pain
      reduction using the visual analog scale was >=82%. The procedure had no adverse
      events or side effects. CONCLUSION: Percutaneous placement of a wireless
      neurostimulation device directly adjacent to affected craniofacial nerve(s) is a
      minimally invasive and reversible method of pain control in patients with
      craniofacial pain refractory to conventional medical managements. Preliminary
      results are encouraging and further larger scale studies are required for
      improved applications.

PMID- 29030174
TI  - Growth hormone protects against kainate excitotoxicity and induces BDNF and NT3
      expression in chicken neuroretinal cells.
AB  - There is increasing evidence to suggest a beneficial neuroprotective effect of
      growth hormone (GH) in the nervous system. While our previous studies have
      largely focused on retinal ganglion cells (RGCs), we have also found conclusive
      evidence of a pro-survival effect of GH in cells of the inner nuclear layer (INL)
      as well as a protective effect on the dendritic trees of the inner plexiform
      layer (IPL) in the retina. The administration of GH in primary neuroretinal cell
      cultures protected and induced neural outgrowths. Our results, both in vitro
      (embryo) and in vivo (postnatal), showed neuroprotective actions of GH against
      kainic acid (KA)-induced excitotoxicity in the chicken neuroretina. Intravitreal
      injections of GH restored brain derived neurotrophic factor (BDNF) expression in
      retinas treated with KA. In addition, we demonstrated that GH over-expression and
      exogenous administration increased BDNF and neurotrophin-3 (NT3) gene expression
      in embryonic neuroretinal cells. Thus, GH neuroprotective actions in neural
      tissues may be mediated by a complex cascade of neurotrophins and growth factors
      which have been classically related to damage prevention and neuroretinal tissue
      repair.

PMID- 29030176
TI  - Physiologically based pharmacokinetic modeling of disposition and drug-drug
      interactions for valproic acid and divalproex.
AB  - Valproic acid (VPA) is an older first-line antiepileptic drug with a complex
      pharmacokinetic (PK) profile, currently under investigation for several novel
      neurologic and non-neurologic indications. Our study objective was to design and
      validate a mechanistic model of VPA disposition in adults and children; and
      evaluate its predictive performance of drug-drug interactions (DDIs). This study
      expands upon existing physiologically based pharmacokinetic (PBPK) models for VPA
      by incorporating UGT enzyme kinetics and an advanced dissolution, absorption, and
      metabolism (ADAM) model for extended-release (ER) formulation. PBPK models for
      VPA IR and ER formulations were constructed using Simcyp Simulator (Version 15).
      First-order absorption was used for the immediate-release (IR) formulation and
      the ADAM model, including a controlled-release profile, for ER. Data from twenty
      one published clinical studies were used to assess model performance. The model
      accurately predicted the concentration-time profiles of IR formulation for single
      dose and steady-state doses ranging from 200mg to 1000mg. Similarly profiles were
      also simulated for ER formulation after a single-dose and steady-state doses of
      500mg and 1000mg, respectively. In addition, simulated PK profiles agreed well
      with the observed data from studies in which VPA ER formulation was given to
      pediatric patients and VPA IR formulation to adult patients with cirrhosis. The
      model was further validated with individual adult data from a Phase I clinical
      trial consisting of eight cohorts after IV infusion of VPA with doses ranging
      from 15 to 150mg/kg. Co-administrations of VPA as an enzyme-inhibitor with victim
      drug phenytoin or lorazepam, as well as a substrate with enzyme inducer
      carbamazepine or phenobarbital, were simulated with the model to evaluate drug
      drug interaction. The simulated serum concentration-time profiles were within the
      5th and 95th percentiles, and the majority of the predicted area-under-the-curve
      (AUC) and peak plasma concentration (Cmax) values were within 25% of the reported
      average values. The comprehensive VPA PBPK model defined by this study may be
      used to support dosage regimen optimization to improve the safety and efficacy
      profile of this agent under different scenarios.

PMID- 29030175
TI  - Characterization of the pleiotropic roles of Sonic Hedgehog during retinal
      regeneration in adult zebrafish.
AB  - In contrast to the mammalian retina, the zebrafish retina possesses the ability
      to regenerate. This is primarily accomplished through Muller glial cells, which,
      upon damage, re-enter the cell cycle to form retinal progenitors. The progenitors
      continue to proliferate as they migrate to the area of damage and ultimately
      differentiate into new neurons. The purpose of this study was to characterize the
      expression and function of Sonic Hedgehog (Shh) during regeneration of the adult
      zebrafish retina. Expression profiling of Shh pathway genes showed a significant
      upregulation of expression associated with stages of progenitor proliferation and
      neuronal differentiation. Activation of Shh signaling during early stages of
      retinal regeneration using intraocular injections of the recombinant human SHH
      (SHH-N) resulted in increased Muller cell gliosis, proliferation, and
      neuroprotection of damaged retinal neurons. Continued activation of Shh resulted
      in a greater number of differentiated amacrine and ganglion cells in the fully
      regenerated retina. Conversely, inhibition of Shh signaling using intraocular
      injections of cyclopamine resulted in decreased Muller glial cell proliferation
      and a fewer number of regenerated amacrine and ganglion cells. These data suggest
      that Shh signaling plays pleiotropic roles in proliferation and differentiation
      during adult zebrafish retinal regeneration.

PMID- 29030177
TI  - Eprosartan mesylate loaded bilosomes as potential nano-carriers against diabetic
      nephropathy in streptozotocin-induced diabetic rats.
AB  - The objective of the present study was to formulate eprosartan mesylate loaded
      nano-bilosomes and investigates its potential for controlling streptozotocin
      induced diabetes nephropathy in Wistar rats. The eprosartan mesylate loaded nano
      bilosomes comprising of various ratios of soybean phosphatidylcholine/sodium
      deoxycholate were prepared by thin film hydration technique. The prepared
      formulations were evaluated for vesicles size, polydispersity index, zeta
      potential and entrapment efficiency. Further the optimized formulation was
      characterized for vesicles morphology, and its efficacy for the management of
      diabetic nephropathy in Wistar rats. The optimized eprosartan mesylate loaded
      nano-bilosomes exhibited vesicles size, polydispersity index, zeta potential and
      entrapment efficiency of 63.88+/-3.46nm, 0.172+/-0.026, -30.40+/-2.75mV and
      61.19+/-0.88% respectively. In vivo activity demonstrated that the prepared
      eprosartan mesylate loaded nano-bilosomes formulation demonstrated a nephro
      protecting outcome as shown by the substantial decrease in serum creatinine,
      urea, lactate dehydrogenase, total albumin, and malondialdehyde. Additionally, an
      oral administration of eprosartan mesylate loaded nano-bilosomes decreases the
      raised expressions of Angiotensin II type 1 receptor, inducible nitric oxide
      synthase, and transforming growth factor-beta1 in Wistar rats. Further,
      histopathological examination established the nephro-protective effect of
      prepared formulation. In conclusion, the research work in the paper suggests that
      the prepared eprosartan mesylate loaded nano-bilosomes could serve as a practical
      oral formulation for diabetic nephropathy in future therapy and may offer
      potential benefits in cases with hypertension and renal disease.

PMID- 29030179
TI  - Designing probe from E6 genome region of human Papillomavirus 16 for sensing
      applications.
AB  - Human Papillomavirus (HPV) is a standout amongst the most commonly reported over
      100 types, among them genotypes 16, 18, 31 and 45 are the high-risk HPV. Herein,
      we designed the oligonucleotide probe for the detection of predominant HPV type
      16 for the sensing applications. Conserved amino acid sequences within E6 region
      of the open reading frame in the HPV genome was used as the basis to design
      oligonucleotide probe to detect cervical cancer. Analyses of E6 amino acid
      sequences from the high-risk HPVs were done to check the percentage of similarity
      and consensus regions that cause different cancers, including cervical cancer.
      Basic local alignment search tools (BLAST) have given extra statistical
      parameters, for example, desire values (E-values) and score bits. The probe, 'GGG
      GTC GGT GGA CCG GTC GAT GTA' was designed with 66.7% GC content. This
      oligonucleotide probe is designed with the length of 24 mer, GC percent is
      between 40 and 70, and the melting point (Tm) is above 50 degrees C. The probe
      needed an acceptable length between 22 and 31 mer. The choice of region is
      identified here can be used as a probe, has implications for HPV detection
      techniques in biosensor especially for clinical determination of cervical cancer.

PMID- 29030178
TI  - A lectin mediated delivery system for the intravesical treatment of bladder
      diseases using poly-(L)-glutamic acid as polymeric backbone.
AB  - In this study, we present a targeted drug delivery system to improve intravesical
      therapy of bladder diseases. The drug delivery system consists of wheat germ
      agglutinin (WGA) to facilitate specific interaction with the surface of bladder
      cells and alpha-poly-(L)-glutamic acid (PGA) as polymeric backbone to increase
      the number of drug molecules per targeting moiety. Additionally, fluorescein
      cadaverine was coupled to PGA to visualise and track the delivery system. Using
      5637 single cells and cell monolayers, the optimised F-PGA-WGA delivery system,
      with an approximate molecular weight of 670kDa, could convince with its promising
      cytoadhesive as well as cytoinvasive potential. Using the competitive inhibitor
      N, N', N"-triacetylchitotriose a specificity of the carbohydrate-mediated
      interaction between the cell and the delivery system of up to 98% was determined.
      F-PGA alone did not show any interaction with the cells. Moreover, a high drug
      loading of 77 molecules of the model drug Dansylcadaverine per backbone was
      achieved. Microscopic analysis further confirmed binding and uptake of the
      cytoadhesive polymer even after additional loading with the model drug. Combining
      the auspicious targeting properties of WGA with the high drug loading
      possibilities of the backbone might finally lead to an enhanced efficacy when
      used for intravesical therapy.

PMID- 29030180
TI  - Designing a direct ELISA kit for the detection of Staphylococcus aureus
      enterotoxin A in raw milk samples.
AB  - Under favorable growth conditions, Staphylococcus aureus infects and causes
      illnesses in humans and animals. Staphylococcal enterotoxins are considered the
      most important factor for food poisoning, with these toxins usually found in milk
      and its byproducts. This study investigated the presence of a classical
      enterotoxin of S. aureus (enterotoxin A) in raw cow milk samples obtained from
      Region 3 of Tehran. Sixty cow milk samples were collected from traditional dairy
      sales centers in the study site. Electrophoresis, high-performance liquid
      chromatography, sandwich ELISA, and direct ELISA were evaluated as methods for
      detecting toxins in the milk. A direct ELISA kit was designed, with the best
      factors, the most suitable densities, and the most optimal temperatures and
      temporal incubation conditions incorporated into the design. Among the evaluated
      methods, direct ELISA exhibited the highest accuracy in toxin detection. The
      designed kit achieved a correctness coefficient of 0.98 and detected enterotoxin
      A in 23% of the samples. It also exhibited a relative sensitivity and other
      features that are comparable to those of other bacterial detection techniques.
      Finally, the kit achieved good matching and repetition results, and no cross
      reactions occurred between enterotoxins during the procedure.

PMID- 29030181
TI  - Use of gelatin and gum Arabic for encapsulation of black raspberry anthocyanins
      by complex coacervation.
AB  - Protein-polysaccharide interactions offer opportunities for designing the new
      functional foods with applications in the food and pharmaceutical industries. In
      this work, we microencapsulated black raspberry water extracts by double emulsion
      technique prior to complex coacervation using gelatin and gum Arabic to diminish
      the instability of their anthocyanins (ANCs) as water soluble compounds,
      particularly under harsh processing and storage conditions. Subsequently, optical
      microscopy, moisture, hygroscopicity, solubility, particle size, loading
      capacity, zeta potential, color parameters (L*, a*, b*, C, H degrees  and TCD),
      stability, Fourier transform infrared spectroscopy (FTIR), and thermal behavior
      were evaluated. The microcapsules presented the lower moisture, hygroscopicity
      and solubility values as comparing the free form of ANCs. They showed the average
      sizes ranging from 35.34+/-3.21 to 80.22+/-5.21MUm and high loading capacity
      (29.67+/-0.66-38.54+/-0.08%). According to the HPLC results, the selected method
      significantly increased the stability of ANCs up to 23.66% after 2 months of
      storage at 37+/-2 degrees C. FT-IR spectra confirmed the negative zeta potential
      values of microcapsules and the occurrence of coacervation process. DSC results
      evidenced the thermostability of microcapsules. Furthermore, the selected optimal
      microcapsules revealed intense red color over the time of storage, implying the
      effectiveness of the method chosen to preserve anthocyanins.

PMID- 29030182
TI  - Biosynthesis of dextran by Weissella confusa and its In vitro functional
      characteristics.
AB  - The aim of this study was to monitor the influence of the fermentation conditions
      on the exopolysaccharides (EPS) biosynthesis. For this, different culture media
      compositions were tested on an isolated lactic acid bacteria (LAB) strain,
      identified by 16S rDNA sequence as being Weissella confusa. It was proved that
      this bacterial strain culture in MRS medium supplemented with 80g/L sucrose and
      dissolved in UHT milk produced up to 25.2g/L of freeze-dried EPS, in static
      conditions, after 48h of fermentative process. Using FTIR and NMR analysis, it
      was demonstrated that the obtained EPS is a dextran. The thermal analysis
      revealed a dextran structure with high purity while GPC analysis depicted more
      fractions, which is normal for a biological obtained polymer. A concentration up
      to 3mg/mL of dextran proved to have no cytotoxic effect on normal human dermal
      fibroblasts (NHDF). Moreover, at this concentration, dextran breaks up to 70% of
      the biofilms formed by the Candida albicans SC5314 strain, and has no
      antimicrobial activity against standard bacterial strains. Due to their
      characteristics, these EPS are suitable as hydrophilic matrix for controlled
      release of drugs in pharmaceutical industry.

PMID- 29030183
TI  - Modification by alpha-d-glucan branching enzyme lowers the in vitro digestibility
      of starch from different sources.
AB  - Granular corn starch, waxy corn starch, potato starch and tapioca starch were
      modified using the alpha-d-glucan branching enzyme (1,4-alpha-d-glucan:1,4-alpha
      d-glucan 6-alpha-d-(1,4-alpha-d-glucano)-transferase, GBE, EC 2.4.1.18) from
      Geobacillus thermoglucosidans. The GBE-catalyzed modification caused a time
      dependent increase in the ratios of alpha-1,6 linkages to total glycosidic
      linkages, as well as reductions in the average chain length and relative
      crystallinity. These modifications lowered the in vitro digestibility of the
      starch. Modification with GBE caused varying degrees of change in the in vitro
      digestibility of starches obtained from different sources. The highest slowly
      digestible starch (SDS) and resistant starch (RS) contents were found in modified
      tapioca starch. After modification of tapioca starch with GBE for 10h, the ratio
      of alpha-1,6 linkages to total glycosidic linkages was increased by 11.5%, while
      its relative crystallinity was decreased by 22.9%. Meanwhile, the SDS and RS
      contents of tapioca starch were increased by 47.3% and 13.5%, respectively. These
      results demonstrate that the digestibility of starch can be lowered through GBE
      modification, which may aid the development of modified starches that are
      digested more slowly.

PMID- 29030184
TI  - Screening of drug-sericin solid dispersions for improved solubility and
      dissolution.
AB  - The aim of present attempt deals with preparation of binary dispersion of
      sericin, waste of sericulture industry in order to enhance solubility and
      dissolution of poorly soluble drugs. Solid dispersions (SDs) of BCS-II drugs were
      prepared by spray drying, solvent evaporation, ball milling and physical mixing
      in ratio of drug:sericin (1:0.5, 1:1, 1:1.5, 1:2, 1:2.5 and 1:3). Further, SDs
      were investigated by solubility, ATR-FTIR, XRD, DSC, micromeritics and
      tablettability, surface morphology and in-vitro dissolution. Results demonstrated
      that, sericin improves solubility of drugs by 8-10 fold. The ATR-FTIR showed the
      slight shifting/broadening of principle peaks corresponding to NH and OH. Spray
      dried (1:2w/w) SDs showed maximum reduction in crystallinity of drugs indicating
      drug was molecularly distributed and was in amorphous state. Spray dried SDs of
      meloxicam showed better compressibility and compactibility. The microphotograph
      of spray dried SDs of lornoxicam and meloxicam showed bowl shaped and blend of
      bowl and spherical particles respectively, while spray dried SDs of felodepine
      showed spherical shape. The spray dried SDs (1:2w/w) displayed better dissolution
      performance than other methods Conclusively, sericin offers a hydrophilic matrix
      to deliver poor water soluble drugs and its aerodynamic shape may show a great
      potential for various drug deliveries.

PMID- 29030185
TI  - Inhibitory effect of tartrate against phosphate-induced DJ-1 aggregation.
AB  - The DJ-1 protein engages in diverse cellular and pathological processes,
      including tumorigenesis, apoptosis, sperm fertilization, and the progression of
      Parkinson's disease (PD). The functional dimeric form of DJ-1 transforms into non
      functional filamentous aggregates in an inorganic phosphate (Pi)-dependent manner
      in vitro. Here, we demonstrated that Pi and reactive oxygen species (ROS) induce
      DJ-1 aggregation in Neuro2A and SH-SY5Y cells. Remarkably, tartrate treatment
      significantly reduced Pi- and ROS-induced DJ-1 aggregation and restored Pi- and
      ROS-provoked cell death using quantitative data as mean+/-standard deviation, and
      statistics. Mechanistically, tartrate prevented DJ-1 aggregation via occupying
      the Pi-binding site. These findings revealed an unexpected physiological role of
      tartrate in the maintenance of DJ-1 function, and thus, a potential use as an
      inhibitor of DJ-1 aggregation.

PMID- 29030186
TI  - Counteraction of the deleterious effects of urea on structure and stability of
      mammalian kidney proteins by osmolytes.
AB  - Owing to the urine concentrating mechanism of kidney cells, urea concentration is
      very high (3.0-5.0M) in mammalian kidneys which may denature many kidney
      proteins. Methylamines are known to counteract the deleterious effects of urea on
      structure, stability and function of proteins at 2:1 molar ratio of urea to
      methylamines. It is known that mammalian kidney cells also contain stabilizing
      osmolytes, non-methylamines (myo-inositol and sorbitol). A question arises: Do
      these non-methylmine osmolytes have ability to counteract the deleterious effects
      of urea on kidney proteins? To answer this question, we took two kidney proteins,
      namely, sheep serum albumin and Human carbonic anhydrase II. We measured their
      thermodynamic stability (DeltaG0N<->D, the Gibbs free energy change in absence of
      GdmCl (guanidinium chloride) associated with the equilibrium, native (N) state<
      >denatured (D) state) from the GdmCl-induced denaturation curves in the presence
      of different concentrations of urea and each kidney osmolyte individually and in
      combination. For both proteins, we observed that (i) glycine betaine and myo
      inositol provide perfect counteraction at 2:1 molar ratio of urea to osmolyte,
      i.e., denaturing effect of 2M urea is 100% neutralized by 1M of glycine betaine
      (or myo-inositol), and (ii) sorbitol fails to refold urea denatured proteins.

PMID- 29030187
TI  - Not only tendons: The other architecture of collagen fibrils.
AB  - For many decades the fibrillar collagens have been the subject of a remarkable
      body of ultrastructural research. The vast majority of the studies, however, were
      carried out on tendon or on tendon-derived material. For many reasons this
      reflects an obvious choice but at the same time it also is an unfortunate
      circumstance, because this flooding of tendon-related data can easily encourage
      the false confidence that all connective tissues are similar. The reality is
      quite the opposite, and a different fibrillar structure has been long time
      observed on collagen fibrils from different tissues, the most notable example
      being offered by corneal fibrils. The same architecture can be found in a number
      of disparate tissues and may actually be the prevalent one on a whole-body scale.
      Although these fibrils diverge from those of tendon in their architecture, size,
      D-period, composition, cross-linking and fibrillogenesis mechanism, their
      structure was the subject of rather sparse ultrastructural studies and even today
      their mere existence is often overlooked or ignored. This paper summarizes the
      main aspects of the structural biology of these forgotten fibrils.

PMID- 29030188
TI  - The green fabrication, characterization and evaluation of catalytic antioxidation
      of gold nanoparticle-lignocellulose composite papers for active packaging.
AB  - Gold nanoparticles (AuNPs) were directly synthesized and anchored on
      lignocellulose fiber without an external immobilizing agent via a facile green
      approach using unbleached kraft (UBK) softwood pulp. The obtained AuNPs were
      confirmed by UV-vis diffuse reflectance spectroscopy, field-emission scanning
      electron microscopy, energy dispersive spectroscopy, X-ray diffraction, Fourier
      transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The
      antioxidant behavior of the as-prepared AuNP-UBK fiber nanocomposite was
      evaluated by free radical scavenging of 2,2-diphenyl-1-picrylhydrazyl hydrate
      (DPPH). The nanocomposite fiber exhibited greatly enhanced radical scavenging
      activity compared to that of the pure fiber. As a consequence, AuNP-UBK
      nanocomposite paper showed exceptional antioxidant performance with a radical
      scavenging rate of over 98%, which is attributed to the synergistic effects of
      adsorption by the fiber-fiber network and subsequent catalytic activity of the
      AuNPs. This research indicated that AuNP-UBK fiber nanocomposites could be a new
      candidate for antioxidant active packaging for use in food preservation.

PMID- 29030189
TI  - Thermostabilization of a thermophilic 1,4-alpha-glucan branching enzyme through C
      terminal truncation.
AB  - Thermophilic proteins are useful for the detailed investigation of
      thermostability because they function efficiently at high temperatures.
      Comparison of the amino acid sequences and three-dimensional structures of
      mesophilic and thermophilic 1,4-alpha-glucan branching enzymes (GBEs) shows that
      the amino acid sequence of the last 26 residues at the C-terminal end of the GBE
      from Geobacillus thermoglucosidans STB02 (GBEGt, GenBank accession no. KJ660983)
      are not conserved, and that their 3-dimensional structure is flexible. These
      residues appear to be modified based upon a balance between flexibility and
      rigidity that is related to thermostability. In this study, a truncated mutant of
      GBEGt made by removing the last 26 residues from its C-terminal end was found to
      have increased thermostability and solubility, compared with the wild-type
      enzyme. Additionally, truncation of a portion of the C-terminus resulted in a
      decrease in aqueous stability. The circular dichroism spectra of GBEGt and
      GBEGtDeltaC were also found to be different. These results suggest that deletion
      of flexible residues at the C-terminal end of GBEGt, which are located on the
      surface of the enzyme, enhances the thermostability of the enzyme without
      significantly compromising its enzymatic activity.

PMID- 29030190
TI  - Design of a pH-sensitive magnetic composite hydrogel based on salecan graft
      copolymer and Fe3O4@SiO2 nanoparticles as drug carrier.
AB  - Salecan, a novel water-soluble extracellular beta-glucan, is very suitable for
      the hydrogel preparation. Here, pH-sensitive magnetic composite hydrogel was
      fabricated by the graft copolymerization of crotonic acid (CA) and N
      (hydroxymethyl) acrylamide (HMAA) onto salecan in the presence of Fe3O4@SiO2
      nanoparticles for doxorubicin (DOX) delivery. The embedment of Fe3O4@SiO2
      nanoparticles into salecan-g-poly(CA-co-HMAA) hydrogel network endowed the
      material with magnetic property. In addition, DOX not only achieved effectively
      bound to the composite hydrogel, but also released in a controlled and pH
      dependent manner. The application of an external magnetic field could
      significantly enhance the drug release rate. More importantly, the released DOX
      preserved its bioavailability. Taken together, these hydrogel drug carriers
      provide a promising platform for magnetically targeted drug delivery.

PMID- 29030191
TI  - Effect of pH and surfactant on the protein: A perspective from theory and
      experiments.
AB  - In the present study, we are aimed to explore the bovine serum albumin (BSA) and
      sodium dodecyl sulfate (SDS) the interaction that can readily show the
      consequence of the change in concentration of protein with surfactants' various
      concentration and the different pH's, 4.0, 4.7, 7.0 of the medium through the
      many spectroscopic techniques. The BSA and SDS denaturation fully influenced by
      the pH. The results interpreted in terms of electrostatic and hydrophobic
      contributions to the stability of different phases formed in the system. Critical
      Micelle Concentration (CMC) of surfactant is influenced the protein folding and
      unfolding. The molecular docking supports the experiment data. This study
      demonstrates that the above and below the CMC of surfactant can significantly
      alter the binding interaction with the protein.

PMID- 29030192
TI  - Polyvinyl alcohol/Sodium alginate integrated silver nanoparticles as probable
      solution for decontamination of microbes contaminated water.
AB  - It is well known that the pathogenic multidrug resistant microbes are highly
      distributed and transferred to human through contaminated food and water.
      Advanced technologies have been developed for controlling these microbes using
      synthesized nanoparticles. In this study, biosynthesized silver nanoparticles
      were prepared, characterized and integrated with two synthetic and natural
      polymers. The polymers-silver nanoparticles were characterized using SEM, FTIR
      and mechanical properties of the membrane synthesized from either polymers
      with/without nanosilver. Both of pathogenic bacteria and yeast were tested for
      their resistance against 10 different antibiotics. The pathogens showed high
      resistance against 9 antibiotics and only one was recorded as potent. The
      cytotoxicity of nanosilver integrated polymers were tested against Hamster kidney
      cells and Human skin fibroblast cells, and the non-cytotoxic dose was checked for
      its antimicrobial activity against the selected pathogens. The obtained results
      in this study confirm that the using of the nanomaterials in safe doses could be
      a good substitution for biogenic antibiotics and chemicals used in water
      treatment. Moreover, the beads which were used in this study could be lasts for
      long period in water treatment station with high antibacterial capacity, in
      addition, it can be gathered easily at the end of the run.

PMID- 29030193
TI  - Inhibitory mechanism of two allosteric inhibitors, oleanolic acid and ursolic
      acid on alpha-glucosidase.
AB  - Glycemic control which can be efficaciously regulated by inhibiting alpha
      glucosidase activity is an effective therapy for diabetes mellitus. This work is
      to investigate the kinetics and inhibition mechanism of oleanolic acid and
      ursolic acid on alpha-glucosidase. Oleanolic acid and ursolic acid exhibited
      potent inhibitory activities with IC50 values of (6.35+/-0.02)*10-6 and (1.69+/
      0.03)*10-5molL-1 respectively in a reversible and non-competitive manner. Both of
      them binding to alpha-glucosidase induced the conformational change and intrinsic
      fluorescence quenching of alpha-glucosidase. The binding constants of oleanolic
      acid and ursolic acid with alpha-glucosidase at 298K were (2.04+/-0.02)*103 and
      (1.87+/-0.02)*103Lmol-1, respectively. Docking results showed that oleanolic acid
      and ursolic acid bound in different allosteric sites of cavity 2 and cavity 4 on
      alpha-glucosidase, respectively, which triggered allosteric regulation to perturb
      conformational dynamics of alpha-glucosidase, eventually leading to a decrease of
      catalytic activity of the enzyme. The substrate was not catalyzed by alpha
      glucosidase to generate further products due to formation of a nonreactive
      ternary complex of oleanolic acid- or ursolic acid-alpha-glucosidase-substrate.
      The combination of oleanolic acid and ursolic acid displayed a significant
      synergistic inhibition on alpha-glucosidase.

PMID- 29030194
TI  - Doughnut-shaped bovine serum albumin nanoparticles loaded with doxorubicin for
      overcoming multidrug-resistant in cancer cells.
AB  - Traditional spherical albumin nanoparticles remain as the dominant shape of nano
      carriers described in the literature at present, due to their simple desolvation
      method of synthesis. However, non-spherical shapes also show great promise as
      cancer drug delivery vectors. In this study, we report a novel synthetic strategy
      based on dimethyl sulfoxide (DMSO) addition during desolvation step, to produce
      doughnut-shaped bovine serum albumin nanoparticles (DBSA-NPs), while maintaining
      narrow size distributions and homogeneity. The characteristics such as size,
      polydispersity and doxorubicin loading of prepared DBSA-NPs in comparison with
      spherical ones were determined. The biodegradation of DBSA-NPs loaded with
      doxorubicin (Dox-DBSA-NPs) in the presence of trypsin enzyme was
      spectrophotometrically monitored directly based on doxorubicin release profile.
      The release profile was analyzed with different kinetic models and it was best
      fitted with Higuchi kinetics model. The anticancer effect of Dox-DBSA-NPs against
      lymphoblastic leukemia (MOLT-4) and multidrug resistant uterine sarcoma (MES
      SA/DX-5) cell lines were also investigated and the results were comparable with
      doxorubicin loaded spherical BSA nanoparticles. These results showed the
      potential of Dox-DBSA-NPs as a novel and high potential nano-carrier for
      management of non-resistance and also multidrug resistant cancer cells.

PMID- 29030195
TI  - Improvement of the catalytic characteristics of a salt-tolerant GH10 xylanase
      from Streptomyce rochei L10904.
AB  - A GH10 xylanase Srxyn10 from Streptomyce rochei L10904, and its truncated
      derivative, Srxyn10M, were investigated. Both displayed great salt-tolerant
      ability, retaining more than 95% and 91% activity after incubation at 37 degrees
      C for 1h in 3.0M and 5.0M NaCl, respectively. They exhibited a special hydrolytic
      property of forming xylobiose as the major product and produced fewer xylose
      compounds when combined with a reported xylanase while digesting corncob xylans.
      The mutant, Srxyn10M, was constructed from Srxyn10 by deleting the C-terminal
      carbohydrate-binding module. It possessed a 3.26-fold higher specific activity on
      beechwood xylan than Srxyn10. Moreover, Srxyn10M showed greater substrate
      affinity and catalytic efficiency than Srxyn10 when beechwood xylan, birchwood
      xylan, and oat-spelt xylan were used as substrates. The thermostability was also
      greatly improved. Therefore, the application potential was markedly enhanced by
      the improvement of these properties.

PMID- 29030196
TI  - Thiosemicarbazide and thiocarbohydrazide functionalized chitosan as ecofriendly
      corrosion inhibitors for carbon steel in hydrochloric acid solution.
AB  - Organically functionalized chitosan macromolecules namely Chitosan
      Thiosemicarbazide (CS-TS) and Chitosan-Thiocarbohydrazide (CS-TCH) were
      synthesized and evaluated as new corrosion inhibitors for mild steel corrosion in
      1M HCl. The FTIR and 1H NMR studies confirmed the formation of the derivatives.
      The corrosion tests were performed using weight loss method, electrochemical
      measurements, surface morphology (AFM), quantum chemical investigation and
      molecular dynamics simulation methods. The maximum efficiency of 92% was obtained
      at a concentration as low as 200mgL-1. The inhibitors were found to obey Langmuir
      adsorption isotherm and exhibited both physical and chemical adsorption.
      Electrochemical impedance spectroscopy (EIS) results showed an increase in
      polarization resistance which supported the adsorption of inhibitors on the mild
      steel surface. Tafel data showed a mixed type behavior with cathodic
      predominance. The data of quantum chemical calculations and molecular dynamics
      simulation supported the experimental findings.

PMID- 29030197
TI  - Green synthesis of degradable conductive thermosensitive oligopyrrole/chitosan
      hydrogel intended for cartilage tissue engineering.
AB  - Electroactive scaffolds containing conductive polymers can promote tissue repair
      and regeneration. However, these polymers are non-degradable and cannot be
      removed from body. To overcome this limitation of conductive polymers, we
      developed a novel injectable electroactive hydrogel containing pyrrole oligomers
      which possessed the unique properties of being both electrically conductive and
      biodegradable. First, pyrrole oligomers were synthesized via chemical
      polymerization and were found to be amorphous with a non-globular morphology.
      Then, three different compositions of injectable chitosan/beta glycerophosphate
      hydrogels containing different concentrations of pyrrole oligomers were
      synthesized and characterized for chemical structure, morphology, conductivity,
      swelling ratio, In vitro biodegradation and gelation time. An increase in
      oligopyrrole content resulted in decreased pore size, and increased gelation
      time, swelling ratio, conductivity and degradation time. Among all the hydrogel
      compositions, the sample with pyrrole oligomer:chitosan ratio of 0.1 (w/w) showed
      the most prominent biodegradability, biocompatibility, electro-activity, swelling
      ratio and pore size values and was chosen as the optimal electroactive hydrogel
      composition in this work.

PMID- 29030198
TI  - Potential of ionic liquids for inhibiting the growth and beta-lactamase
      production by Bacillus cereus EMB20.
AB  - Present work reports the inhibition of Bacillus cereus EMB20 beta-lactamase by a
      deep eutectic solvent, maline in an uncompetitive manner. Far-UV CD and intrinsic
      fluorescence spectroscopy revealed a disrupted secondary as well as tertiary
      structure as a function of maline concentration. The effect of individual
      components of maline on beta-lactamase inhibition showed that malonic acid was
      mainly responsible for inhibiting the beta-lactamase. Structural and docking
      studies found that malonic acid led to major perturbations in the secondary and
      tertiary structure of the enzyme while H-bonding with the active site residues.
      Further the antibacterial and cytotoxic studies also confirmed the potential of
      maline as a potent growth inhibitor of beta-lactamase producing B. cereus EMB20.

PMID- 29030200
TI  - Iodine supplementation in pregnancy in mildly deficient regions.

PMID- 29030199
TI  - Effect of iodine supplementation in pregnant women on child neurodevelopment: a
      randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Iodine deficiency during pregnancy might be associated with reduced
      intelligence quotient (IQ) score in offspring. We assessed the effect of iodine
      supplementation in mildly iodine-deficient pregnant women on neurodevelopment of
      their offspring in areas where schoolchildren were iodine sufficient. METHODS: In
      this randomised, placebo-controlled trial, pregnant women in Bangalore, India,
      and Bangkok, Thailand, were randomly assigned (1:1) to receive 200 MUg iodine
      orally once a day or placebo until delivery. Randomisation was done with a
      computer-generated sequence and stratified by site. Co-primary outcomes were
      verbal and performance IQ scores on the Wechsler Preschool and Primary Scale of
      Intelligence Third Edition (WPPSI-III) and the global executive composite score
      from the Behaviour Rating Inventory of Executive Function-Preschool Version
      (BRIEF-P) in the children at age 5-6 years. The trial was double-blinded; some
      unmasking took place at age 2 years for an interim analysis, but participants and
      nearly all investigators remained masked to group assignment until age 5-6 years.
      Analysis was by intention to treat using mixed-effects models. This trial is
      registered with ClinicalTrials.gov, number NCT00791466. FINDINGS: Between Nov 18,
      2008, and March 12, 2011, 832 women entered the trial at a mean gestational age
      of 10.7 weeks (SD 2.7); median urinary iodine concentration was 131 MUg/L (IQR 81
      213). Mean compliance with supplementation was 87%, assessed by monthly tablet
      counts. 313 children (iodine group, n=159; placebo group, n=154) were analysed
      for verbal and performance IQ with WPPSI-III and 315 (iodine group, n=159;
      placebo group, n=156) for overall executive function with BRIEF-P. Mean WPPSI-III
      scores for verbal IQ were 89.5 (SD 9.8) in the iodine group and 90.2 (9.8) in the
      placebo group (difference -0.7, 95% CI -2.9 to 1.5; p=0.77), and for performance
      IQ were 97.5 (12.5) in the iodine group and 99.1 (13.4) in the placebo group
      (difference -1.6, -4.5 to 1.3; p=0.44). The mean BRIEF-P global executive
      composite score was 90.6 (26.2) in the iodine group and 91.5 (27.0) in the
      placebo group (difference -0.9, -6.8 to 5.0; p=0.74). The frequency of adverse
      events did not differ between groups during gestation or at delivery: 24 women in
      the iodine group and 28 in the placebo group reported adverse events (iodine
      group: abortion, n=20; blighted ovum, and n=2; intrauterine death, n=2; placebo
      group: abortion, n=22; blighted ovum, n=1; intrauterine death, n=2; early
      neonatal death, n=1; and neonatal death, n=2). INTERPRETATION: Daily iodine
      supplementation in mildly iodine-deficient pregnant women had no effect on child
      neurodevelopment at age 5-6 years. FUNDING: Swiss National Science Foundation,
      Nestle Foundation, Wageningen University and Research, and ETH Zurich.

PMID- 29030201
TI  - SGLT2 inhibitors: hypotheses on the mechanism of cardiovascular protection.

PMID- 29030202
TI  - Improving the clinical impact of randomised trials in thyroidology.

PMID- 29030203
TI  - Characterization and clinical evaluation of a novel 2D detector array for
      conventional and flattening filter free (FFF) IMRT pre-treatment verification.
AB  - BACKGROUND AND PURPOSE: The novel MatriXXFFF (IBA Dosimetry, Germany) detector is
      a new 2D ionization chamber detector array designed for patient specific IMRT
      plan verification including flattening-filter-free (FFF) beams. This study
      provides a detailed analysis of the characterization and clinical evaluation of
      the new detector array. MATERIAL AND METHODS: The verification of the MatriXXFFF
      was subdivided into (i) physical dosimetric tests including dose linearity, dose
      rate dependency and output factor measurements and (ii) patient specific IMRT pre
      treatment plan verifications. The MatriXXFFF measurements were compared to the
      calculated dose distribution of a commissioned treatment planning system by gamma
      index and dose difference evaluations for 18 IMRT-sequences. All IMRT-sequences
      were measured with original gantry angles and with collapsing all beams to 0
      degrees  gantry angle to exclude the influence of the detector's angle
      dependency. RESULTS: The MatriXXFFF was found to be linear and dose rate
      independent for all investigated modalities (deviations <=0.6%). Furthermore, the
      output measurements of the MatriXXFFF were in very good agreement to reference
      measurements (deviations <=1.8%). For the clinical evaluation an average pixel
      passing rate for gamma(3%,3mm) of (98.5+/-1.5)% was achieved when applying a
      gantry angle correction. Also, with collapsing all beams to 0 degrees  gantry
      angle an excellent agreement to the calculated dose distribution was observed
      (gamma(3%,3mm)=(99.1+/-1.1)%). CONCLUSIONS: The MatriXXFFF fulfills all physical
      requirements in terms of dosimetric accuracy. Furthermore, the evaluation of the
      IMRT-plan measurements showed that the detector particularly together with the
      gantry angle correction is a reliable device for IMRT-plan verification including
      FFF.

PMID- 29030204
TI  - Interarterial Coronary Tract: Presumptive Echocardiographic Diagnosis.

PMID- 29030205
TI  - Large Congenital Coronary Fistula.

PMID- 29030207
TI  - Clinical Variety May Help Prevent Burnout After a Decade in Palliative Care.

PMID- 29030206
TI  - The Impact of Supporting Family Caregivers Before Bereavement on Outcomes After
      Bereavement: Adequacy of End-of-Life Support and Achievement of Preferred Place
      of Death.
AB  - CONTEXT: The investigation of the situation of bereaved family caregivers
      following caregiving during the end-of-life phase of illness has not received
      enough attention. OBJECTIVES: This study investigated the extent to which using
      the Carer Support Needs Assessment Tool (CSNAT) intervention during the
      caregiving period has affected bereaved family caregivers' perceptions of
      adequacy of support, their grief and well-being, and achievement of their
      preferred place of death. METHOD: All family caregivers who participated in a
      stepped-wedge cluster trial of the CSNAT intervention in Western Australia (2012
      2014) and completed the pre-bereavement study (n = 322) were invited to take part
      in a caregiver survey by telephone four to six months after bereavement (2015).
      The survey measured the adequacy of end-of-life support, the level of grief, the
      current physical and mental health, and the achievement of the preferred place of
      death. RESULTS: The response rate was 66% (152, intervention; 60, control). The
      intervention group perceived that their pre-bereavement support needs had been
      adequately met to a significantly greater extent than the control group (d =
      0.43, P < 0.001) and that patients have achieved their preferred place of death
      more often according to their caregivers (79.6% vs. 63.6%, P = 0.034). There was
      also a greater agreement on the preferred place of death between patients and
      their caregivers in the intervention group (P = 0.02). CONCLUSIONS: The results
      from this study provide evidence that the CSNAT intervention has a positive
      impact on perceived adequacy of support of bereaved family caregivers and
      achievement of preferred place of death according to caregivers. The benefits
      gained by caregivers in being engaged in early and direct assessment of their
      support needs before bereavement reinforce the need for palliative care services
      to effectively support caregivers well before the patient's death.

PMID- 29030208
TI  - Addressing a Patient's Hope for a Miracle.
AB  - Ill patients may make decisions to continue aggressive life-prolonging care based
      on hope for a miraculous recovery, and clinicians can find goals of care
      discussions with these patients extremely challenging. Thus, palliative care
      providers may be asked to help in these discussions. The concept of "miracle" can
      express a multitude of hopes, fears, and religious commitments. Effective,
      sensitive engagement requires the palliative care provider to attend to these
      variegated hopes, fears, and commitments. This case presents a typology of ways
      patients express hope for a miracle along with analysis of the motivations and
      beliefs underlying such hopes and suggestions for tailored responses by
      palliative care providers.

PMID- 29030209
TI  - Oncologists' and Patients' Perceptions of Initial, Intermediate, and Final Goals
      of Care Conversations.
AB  - CONTEXT: Although recommendations are for goals of care (GoC) conversations to
      happen early and often, their timing and content over the disease course remain
      unclear. OBJECTIVES: To describe perceptions of the timing and content of GoC
      conversations among oncologists and patients with advanced cancer. METHODS: Semi
      structured interviews with oncologists and patients at four hospitals in New York
      and Connecticut. We analyzed data using interpretive description. RESULTS:
      Oncologists (n = 21) were 67% male, averaged 46 years old (range 34-68 years),
      and had a mean 20 years (range 8-42 years) in practice. Advanced cancer patients
      (n = 39) were 59% female with a mean age of 58 years (range 26-88 years).
      Oncologists and patients viewed GoC conversations along an initial, intermediate,
      and final continuum. Oncologists reported having initial GoC conversations to
      build rapport, provide disease information, and clarify and consider treatment
      intent and options. Intermediate conversations focused on changes in treatment
      and side effects. Final conversations occurred when patients were hospice
      eligible and covered the shift to comfort care, a treatment summary, and advance
      directives. Timing and content were influenced by cancer type, disease status,
      and emotional state. Patients supported beginning GoC conversations early, but
      had different preferences for content of initial conversations. Some wanted
      complete information; others found this overwhelming. Patients felt intermediate
      GoC conversations should occur at decision points with time for processing.
      Content of intermediate and final conversations was dependent on patients'
      prognosis, questions, and treatment decisions. CONCLUSION: Although GoC
      conversations should follow individual patient preferences, our findings offer
      structure for their timing and content.

PMID- 29030210
TI  - Continuous Cardiac Inotropes in Patients With End-Stage Heart Failure: An
      Evolving Experience.
AB  - Heart failure (HF) experts recommend initiation of continuous inotrope therapy,
      such as milrinone or dobutamine, for clinically decompensating patients with
      stage D HF. Although originally intended to serve solely as a bridge to more
      definitive surgical therapies, more and more patients are receiving inotrope
      therapy for purely palliative purposes. In these cases, questions arise regarding
      care at the end of life. What criteria determine ongoing clinical benefit? Should
      the inotrope be continued until death? Should inotrope dosing be increased within
      recommended guidelines to improve symptoms? What is the role of inotropes in
      hospice care? Here, we describe such a case as a springboard to contemplate the
      evolving role of inotrope therapies and how hospice and palliative providers may
      interface with this rapidly developing face of advanced HF care.

PMID- 29030211
TI  - Identifying Opportunities to Improve Pain Among Patients With Serious Illness.
AB  - CONTEXT: Pain is a common and distressing symptom. Pain management is a core
      competency for palliative care (PC) teams. OBJECTIVE: Identify characteristics
      associated with pain and pain improvement among inpatients referred to PC.
      METHODS: Thirty-eight inpatient PC teams in the Palliative Care Quality Network
      entered data about patients seen between December 12, 2012 and March 15, 2016. We
      examined patient and care characteristics associated with pain and pain
      improvement. RESULTS: Of patients who could self-report symptoms, 30.7% (4959 of
      16,158) reported moderate-to-severe pain at first assessment. Over 40% of these
      patients had not been referred to PC for pain. Younger patients (P < 0.0001),
      women (P < 0.0001), patients with cancer (P < 0.0001), and patients in
      medical/surgical units (P < 0.0001) were more likely to report pain. Patients
      with pain had higher rates of anxiety (P < 0.0001), nausea (P < 0.0001), and
      dyspnea (P < 0.0001). Sixty-eight percent of patients with moderate-to-severe
      pain improved by the PC team's second assessment within 72 hours; 74.7% improved
      by final assessment. There was a significant variation in the rate of pain
      improvement between PC teams (P < 0.0001). Improvement in pain was associated
      with improvement in anxiety (OR = 2.9, P < 0.0001) and dyspnea (OR = 1.4, P =
      0.03). Patients who reported an improvement in pain had shorter hospital length
      of-stay by two days (P = 0.003). CONCLUSION: Pain is common among inpatients
      referred to PC. Three-quarters of patients with pain improve and improvement in
      pain is associated with other symptom improvement. Standardized, multisite data
      collection can identify PC patients likely to have marked and refractory pain,
      create benchmarks for the field, and identify best practices to inform quality
      improvement.

PMID- 29030213
TI  - Integrate and fire model with refractory period for synchronization of two
      cardiomyocytes.
AB  - We investigate an integrate and fire model for two cardiomyocytes interacting
      with each other. A feature of the model is to incorporate the refractory periods
      of the cardiomyocytes as well as the influence of firing of adjacent cells. The
      present model predicts that, if refractory periods of the two cells are nearly
      equal, the beating rhythms of the two cells always synchronize and their beating
      rate is tuned to the faster rate between the two cells. On the other hand, if
      their refractory periods significantly differ, they exhibit various kinds of
      harmonious beating rhythms. These results successfully explain the well known
      characteristics of synchronized beating of cultured cardiomyocytes. We also
      discuss effects of a delay time of cell-to-cell interaction, that gives further
      complicated phase diagrams for the beating rhythms.

PMID- 29030212
TI  - Modeling the chemotherapy-induced selection of drug-resistant traits during tumor
      growth.
AB  - The emergence of drug-resistance is a major challenge in chemotherapy. In this
      paper we develop a mathematical model to study the dynamics of drug-resistance in
      solid tumors. Our model follows the dynamics of the tumor, assuming that the
      cancer cell population depends on a phenotype variable that corresponds to the
      resistance level to a cytotoxic drug. The equation for the tumor density is
      written as a reaction-diffusion equation with a pressure term that depends on the
      local cell density. The model incorporates the dynamics of nutrients and two
      different types of drugs: a cytotoxic drug, which directly impacts the death rate
      of the cancer cells, and a cytostatic drug that reduces the proliferation rate.
      This model successfully integrates the phenotype structured drug-resistance
      approach with an asymmetric tumor growth model in space. Through analysis and
      simulations we study the impact of spatial and phenotypic heterogeneity on the
      tumor growth under chemotherapy. We demonstrate that heterogeneous cancer cells
      may emerge due to the selection dynamics of the environment. Our model predicts
      that under certain conditions, multiple resistant traits emerge at different
      locations within the tumor. We show that a higher dosage of the cytotoxic drug
      may delay a relapse, yet, when this happens, a more resistant trait emerges.
      Moreover, we estimate the expansion rate of the tumor boundary as well as the
      time of relapse, in terms of the resistance trait, the level of the nutrient, and
      the drug concentration. Finally, we propose an efficient drug schedule aiming at
      minimizing the growth rate of the most resistant trait. By combining the
      cytotoxic and cytostatic drugs, we demonstrate that the resistant cells can be
      eliminated.

PMID- 29030214
TI  - Fisher's fundamental theorem of natural selection, dynamic sufficiency, and the
      necessity of higher moments.
AB  - The "average effects" of alleles in Fisher's Fundamental Theorem of Natural
      Selection are meant to capture what having an allele does to fitness. These
      average effects however are generally not constant, because the way they are
      determined implies that they may depend on the composition of the current
      population. This can easily be mistaken for dynamic insufficiency. In a recent
      paper by Smerlak and Youssef (2017), both of these issues are moreover treated as
      related to the question whether or not there is a way around needing all higher
      moments for determining the long run behavior of a dynamical system. In this note
      I will argue that these are three unrelated issues.

PMID- 29030215
TI  - Analyzing cost-effectiveness of neural-monitoring in recurrent laryngeal nerve
      recovery course in thyroid surgery.
AB  - PURPOSE: The increasing use of intraoperative neural monitoring (IONM) of the
      recurrent laryngeal nerve (RLN) during thyroid surgery imposes an evaluation of
      cost-effectiveness. METHODS: The analysis estimated the cost versus utility of
      different alternatives that simulate nerve injury course and the consequences for
      the following cohorts of patients: (1) no RLN injury, or vocal fold palsy (VCP)
      recovery within 1 month (2), 2 months (3), 6 months (4), and after 12 months (5).
      In the model applied, the average simulated cohort consisted of a young female
      patient, 40 years old, employed, daily voice user, who underwent elective,
      conventional total thyroidectomy via cervical incision using a standardized
      intermittent IONM technique, for an operable benign, bilateral, diffuse,
      multinodular, non-toxic, non-retrosternal goiter. RESULTS: IONM was cost
      ineffective when parameters such as the rates of transient vocal fold palsy (VCP)
      reached 38.5%. IONM was cost-effective if the rate of VCP was 33.6% at 1 month,
      22.9% at 2 months, 9.8% at 6 months, and 3.8% at 12 months, independent of phono
      surgery. The described scenario is cost-effective only in a high-volume setting.
      CONCLUSIONS: This study used simulation economic modeling to assess clinical and
      cost-effectiveness utility of IONM implementation. In light of the limitations of
      a simulation-based study, we conclusively assumed that IONM is cost-effective for
      permeant RLN injuries.

PMID- 29030216
TI  - Disrupted physiological reactivity among children with a history of suicidal
      ideation: Moderation by parental expressed emotion-criticism.
AB  - OBJECTIVE: The goal of this study was to examine physiological reactivity during
      parent-child interactions in children with and without a history of suicidal
      ideation (SI), a group known to be at increased risk for suicidal thoughts and
      behaviors in the future. We also examined the potential moderating role of
      parental expressed emotion-criticism (EE-Crit) to determine whether the presence
      of parental criticism may help to identify a subgroup of children with a history
      of SI most at risk for physiological dysregulation. METHOD: Participants were 396
      children (age 7-11; 54% male, 71.7% Caucasian) and their biological parent.
      Children's levels of high frequency heart rate variability (HF-HRV) were assessed
      during a resting baseline period followed by a positive and negative discussion
      with their parent. Additionally, parents completed the Five-Minute Speech Sample
      to determine levels of EE-Crit toward their child, and children completed an
      interview assessing their history of SI. RESULTS: Consistent with our hypothesis,
      we found that exposure to parental criticism moderated the relation between a
      child's history of SI and their HF-HRV reactivity to the discussions.
      Specifically, while most children exhibited the typical pattern of HF-HRV
      suppression from baseline to both interactions, the highest risk children (i.e.,
      children with a history of SI who also had highly critical parents) did not
      display any change in HF-HRV across the tasks, suggesting a failure to engage a
      typical psychophysiological response during emotional contexts. CONCLUSIONS:
      These results suggest a specific physiological mechanism that may place these
      children at risk for suicidal thoughts and behaviors in the future.

PMID- 29030217
TI  - Impact of peripheral immune status on central molecular responses to facial nerve
      axotomy.
AB  - When facial nerve axotomy (FNA) is performed on immunodeficient recombinase
      activating gene-2 knockout (RAG-2-/-) mice, there is greater facial motoneuron
      (FMN) death relative to wild type (WT) mice. Reconstituting RAG-2-/- mice with
      whole splenocytes rescues FMN survival after FNA, and CD4+ T cells specifically
      drive immune-mediated neuroprotection. Evidence suggests that immunodysregulation
      may contribute to motoneuron death in amyotrophic lateral sclerosis (ALS).
      Immunoreconstitution of RAG-2-/- mice with lymphocytes from the mutant superoxide
      dismutase (mSOD1) mouse model of ALS revealed that the mSOD1 whole splenocyte
      environment suppresses mSOD1 CD4+ T cell-mediated neuroprotection after FNA. The
      objective of the current study was to characterize the effect of CD4+ T cells on
      the central molecular response to FNA and then identify if mSOD1 whole
      splenocytes blocked these regulatory pathways. Gene expression profiles of the
      axotomized facial motor nucleus were assessed from RAG-2-/- mice
      immunoreconstituted with either CD4+ T cells or whole splenocytes from WT or
      mSOD1 donors. The findings indicate that immunodeficient mice have suppressed
      glial activation after axotomy, and cell transfer of WT CD4+ T cells rescues
      microenvironment responses. Additionally, mSOD1 whole splenocyte recipients
      exhibit an increased astrocyte activation response to FNA. In RAG-2-/- + mSOD1
      whole splenocyte mice, an elevation of motoneuron-specific Fas cell death
      pathways is also observed. Altogether, these findings suggest that mSOD1 whole
      splenocytes do not suppress mSOD1 CD4+ T cell regulation of the microenvironment,
      and instead, mSOD1 whole splenocytes may promote motoneuron death by either
      promoting a neurotoxic astrocyte phenotype or inducing Fas-mediated cell death
      pathways. This study demonstrates that peripheral immune status significantly
      affects central responses to nerve injury. Future studies will elucidate the
      mechanisms by which mSOD1 whole splenocytes promote cell death and if inhibiting
      this mechanism can preserve motoneuron survival in injury and disease.

PMID- 29030219
TI  - Local infusion of ghrelin into the lateral amygdala blocks extinction of
      conditioned taste aversion in rats.
AB  - Ghrelin is an orexigenic brain-gut hormone promoting feeding and regulating
      energy metabolism in human and rodents. Our previous study showed that ghrelin
      locally infused into the lateral amygdala (LA) activates its receptor GHS-R1a and
      blocks acquisition of conditioned taste aversion (CTA) in rats. In this study, we
      further investigated the effect of ghrelin/GHS-R1a signaling on extinction of
      CTA. We found that local infusion of ghrelin (5MUM, 0.5MUl/side) into the LA not
      only interfered with CTA memory formation, but also the extinction of CTA memory.
      Pre-administration of GHS-R1a antagonist blocked ghrelin's effect on both CTA
      acquisition and extinction. However, pre-treatment with PI3K inhibitor only
      abolished the inhibitory effect of ghrelin on acquisition, but not on extinction.
      Altogether, our data indicated that ghrelin/GHS-R1a signaling in the LA circuit
      modulates both acquisition and extinction of CTA, the two forms of taste aversion
      processes with distinct mechanisms may also share certain molecular and circuit
      components in common.

PMID- 29030218
TI  - Acupuncture suppresses intravenous methamphetamine self-administration through
      GABA receptor's mediation.
AB  - OBJECTIVES: Methamphetamine is one of the widely abused drugs. In spite of a
      number of studies, there is still little successful therapy to suppress the
      methamphetamine abuse. Acupuncture has shown to attenuate the reinforcing effects
      of psychostimulant. Based on, the present study investigated if acupuncture could
      suppress intravenous methamphetamine self-administration behavior. In addition, a
      possible neuronal mechanism was investigated. MATERIALS & METHODS: Male Sprague
      Dawley rats weighing 270-300g were trained to intake food pellet. After catheter
      implantation, animal was trained to self-administer methamphetamine (0.05mg/kg)
      intravenously using fixed ratio 1 schedule in daily 2h session during 3 weeks.
      After training, rats who established baseline (infusion variation less than 20%
      of the mean for 3 consecutive days) received acupuncture treatment on the next
      day. Acupuncture was performed at each acupoint manually. In the second
      experiment, the selective antagonists of GABAA or GABAB receptor were given
      before acupuncture to investigate the possible neuronal involvement of GABA
      receptor pathway in the acupuncture effects. C-Fos expression was examined in the
      nucleus accumbens to support behavioral data. RESULTS: Acupuncture at HT7, but
      not at control acupoint LI5, reduced the self-administration behavior
      significantly. Also, the effects of acupuncture were blocked by the GABA receptor
      antagonists. C-Fos expression was shown to be parallel with the behavioral data.
      CONCLUSIONS: Results of this study have shown that acupuncture at HT7 suppressed
      methamphetamine self-administration through GABA receptor system, suggesting that
      acupuncture at HT7 can be a useful therapy for the treatment of methamphetamine
      abuse.

PMID- 29030220
TI  - The correlation between DNA methylation and transcriptional expression of human
      dopamine transporter in cell lines.
AB  - This study aims to investigate the relationship between DNA methylation and
      expression of human dopamine transporter (hDAT). We examined methylation status
      of hDAT in cells with various hDAT expression levels, including two dopaminergic
      neural cell lines (SK-N-AS and SH-SY-5Y) and one non-dopaminergic cell line
      (HEK293) by bisulfite sequencing PCR(BSP). The effects of DNA methyltransferase
      inhibitor 5-aza-dC or/and histone deacetylase inhibitor (HDACi, sodium butyrate,
      NaB) on the DNA methylation status and mRNA expression levels of hDAT were
      examined. The results revealed marked hypomethylation of the two promoter regions
      (-1214 to -856bp and -48 to 439bp, the first base of exon 1 was taken as +1 bp)of
      hDAT in SK-N-AS (4.7%+/-2.0mC and 3.5%+/-1.0mC, respectively) compared with SH-SY
      5Y (88.0%+/-4.4%mC and 81.1%+/-8.8%mC) and HEK293 (90.7%+/-2.4mC and 84.4%+/-8.6%
      mC) cell lines, indicating a cell-specific methylation regulation of hDAT. 5-aza
      dC and NaB decreased hypermethylation,while increase hDAT expression in SH-SY-5Y
      cells and recovered hDAT mRNA expression in HEK293 cells. DNA methylation enabled
      the cell-specific differential expression of the hDAT gene. hDAT silencing was
      reversed by the introduction of DNA hypomethylation via 5-aza-dC or/and NaB.

PMID- 29030221
TI  - Inhibition of BDNF production by MPP+ through up-regulation of miR-210-3p
      contributes to dopaminergic neuron damage in MPTP model.
AB  - The neurotrophin brain-derived neurotrophic factor (BDNF) has been involved in
      supporting of neuron survival. The observation of reduced level of BDNF in the
      substantia nigra (SN) of Parkinson's disease (PD) patients suggests its important
      role in neuron protection in PD pathogenesis. However, the mechanism underlying
      the down-regulation of BDNF in PD was largely unknown. In this study, we found
      that miR-210-3p is involved in the regulation of BDNF production by 1-methyl-4
      phenylpyridinium (MPP+). MPP+ inhibits the BDNF production in SH-SY5Y cells
      through a transcription independent manner. Moreover, miR-210-3p, which targets
      BDNF mRNA, is up-regulated by MPP+ in SH-SY5Y cells. Importantly, inhibition of
      miR-210-3p prevents the reduction of BDNF production by MPP+ and improves the DA
      neuron survival in 1-methyl-4-phenyl-1,2,3,6-tetra hydropyridine (MPTP) model.
      Together, we demonstrated up-regulation of miR-210-3p by MPP+ reduces the BDNF
      production and contributes to the DA neuron damage.

PMID- 29030223
TI  - 3D printed multi-compartment capsular devices for two-pulse oral drug delivery.
AB  - In the drug delivery area, versatile therapeutic systems intended to yield
      customized combinations of drugs, drug doses and release kinetics have drawn
      increasing attention, especially because of the advantages that personalized
      pharmaceutical treatments would offer. In this respect, a previously proposed
      capsular device able to control the release performance based on its design and
      composition, which could extemporaneously be filled, was improved to include
      multiple separate compartments so that differing active ingredients or
      formulations may be conveyed. The compartments, which may differ in thickness and
      composition, resulted from assembly of two hollow halves through a joint also
      acting as a partition. The systems were manufactured by fused deposition modeling
      (FDM) 3D printing, which holds special potential for product personalization, and
      injection molding (IM) that would enable production on a larger scale. Through
      combination of compartments having wall thickness of 600 or 1200MUm, composed of
      promptly soluble, swellable/erodible or enteric soluble polymers, devices showing
      two-pulse release patterns, consistent with the nature of the starting materials,
      were obtained. Systems fabricated using the two techniques exhibited comparable
      performance, thus proving the prototyping ability of FDM versus IM.

PMID- 29030222
TI  - Vascular changes in tumors resistant to a vascular disrupting nanoparticle
      treatment.
AB  - Anti-angiogenic and vascular disrupting therapies rely on the dependence of
      tumors on new blood vessels to sustain tumor growth. We previously reported a
      potent vascular disrupting agent, a theranostic nanosystem consisting of a tumor
      vasculature-homing peptide (CGKRK) fused to a pro-apoptotic peptide [D(KLAKLAK)2]
      coated on iron oxide nanoparticles. This nanosystem showed promising therapeutic
      efficacy in glioblastoma (GBM) and breast cancer models. However, complete
      control of the tumors was not achieved, and some tumors became non-responsive to
      the treatment. Here we examined the non-responder phenomenon in an aggressive
      MCF10-CA1a breast tumor model. In the treatment-resistant tumors we noted the
      emergence of CD31-negative patent neovessels and a concomitant loss of tumor
      homing of the nanosystem. In vivo phage library screening in mice bearing non
      responder tumors showed that compared to untreated and treatment-sensitive
      tumors, treatment sensitive tumors yield a distinct landscape of vascular homing
      peptides characterized by over-representation of peptides that target alphav
      integrins. Our approach may be generally applicable to the development of
      targeted therapies for tumors that have failed treatment.

PMID- 29030226
TI  - Self-sourced online and self-directed at home: a new frontier for abortion in the
      United States.

PMID- 29030224
TI  - Transfer-molded wrappable microneedle meshes for perivascular drug delivery.
AB  - After surgical procedures such as coronary/peripheral bypass grafting or
      endarterectomy for the treatment of organ ischemia derived from atherosclerosis,
      intimal hyperplasia (IH) which leads to restenosis or occlusion at the site of
      graft anastomosis frequently occurs. In order to inhibit IH caused by abnormal
      growth of smooth muscle cells (SMCs) in tunica media, various perivascular drug
      delivery devices are reported for delivery of anti-proliferation drugs into
      vascular tissue. However, there still remain conflicting requirements such as
      local and unidirectional delivery vs device porosity, and conformal tight device
      installation vs pulsatile expansion and constriction of blood vessels. In this
      study, a biodegradable microneedle (MN) array is developed on a flexible woven
      surgical mesh using a transfer molding method. Mechanical properties of
      'wrappable' MN meshes are investigated and compared to the properties of blood
      vessels. Ex vivo and in vivo animal studies demonstrate enhanced drug delivery
      efficiency, efficacy for IH reduction, and safety of MN mesh. In particular, MN
      mesh showed significantly reduced neointiamal formation (11.1%) compared to other
      competitive groups (23.7 and 22.2%) after 4-week in vivo animal study.
      Additionally, wrappable MN meshes effectively suppressed side effects such as IH
      due to mechanical constriction, loss of toxic drug to the surroundings, and cell
      death that were frequently observed with other previous perivascular drug
      delivery devices.

PMID- 29030225
TI  - An intelligent re-shieldable targeting system for enhanced tumor accumulation.
AB  - Programmed ligand targeting strategy promotes the blood circulation stability of
      nanoparticles by shielding the ligand. However, the irreversible shielding causes
      the deshielded nanoparticles to be easily recognized and cleared by the
      reticuloendothelial system (RES), impeding their further retention in the tumor.
      Here, we for the first time prove the superiority of the intelligent re
      shieldable targeting system that is based on the pH-responsive self
      assembly/disassembly of gold nanoparticles. The system can enhance the stability
      of gold nanoparticles in the blood circulation (2.6-fold at 24h), reduce uptake
      by the RES (35% lower) and improve tumor accumulation (41% higher by analysis of
      gold content in tumor) effectively compared with the conventional irreversible
      system. Furthermore, preliminary study indicates that the system could be applied
      as computed tomography contrast agent in tumor imaging. The in vivo validity of
      the intelligent re-shieldable targeting system provides inspiration for the
      design of nanomaterials for cancer diagnosis and treatment.

PMID- 29030227
TI  - Exploring the feasibility of obtaining mifepristone and misoprostol from the
      internet.
AB  - OBJECTIVES: We aimed to document the experience of buying abortion pills from
      online vendors that do not require a prescription and to evaluate the active
      ingredient content of the pills received. STUDY DESIGN: We searched the internet
      to identify a convenience sample of websites that sold mifepristone and
      misoprostol to purchasers in the United States and attempted to order these
      products. We documented price, shipping time and other aspects of ordering. We
      sent the samples received to a testing laboratory that measured the amount of
      active ingredient in individual tablets. RESULTS: We identified 18 websites and
      ordered 22 products: 20 mifepristone-misoprostol combination products and 2 that
      contained only misoprostol. We received 18 combination products and the 2
      misoprostol products from 16 different sites. No site required a prescription or
      any relevant medical information. The time between order and receipt of the 20
      products ranged from 3 to 21 business days (median 9.5 days). The price for the
      18 combination products ranged from $110 to $360, including shipping and fees;
      the products without mifepristone cost less. Chemical assays found that the 18
      tablets labeled 200 mg mifepristone contained between 184.3 mg and 204.1 mg
      mifepristone, while the 20 tablets labeled 200 mcg misoprostol contained between
      34.1 mcg and 201.4 mcg of the active ingredient. CONCLUSIONS: Obtaining abortion
      medications from online pharmaceutical websites is feasible in the United States.
      The mifepristone tablets received contained within 8% of the labeled amount of
      active agent. The misoprostol tablets all contained that compound but usually
      less than labeled. IMPLICATIONS STATEMENT: Given our findings, we expect that
      some people for whom clinic-based abortion is not easily available or acceptable
      may consider self-sourcing pills from the internet to be a rational option.

PMID- 29030228
TI  - The relation between young children's physiological arousal and their motivation
      to help others.
AB  - Children are motivated to help others from an early age. However, little is known
      about the internal biological mechanisms underlying their motivation to help.
      Here, we compiled data from five separate studies in which children, ranging in
      age from 18 months to 5.5 years, witnessed an adult needing help. In all studies,
      we assessed both (1) children's internal physiological arousal via changes in
      their pupil dilation, and (2) the latency and likelihood of them providing help.
      The results showed that the greater the baseline-corrected change in children's
      internal arousal in response to witnessing the need situation, the faster and
      more likely children were to help the adult. This was not the case for the
      baseline measure of children's tonic arousal state. Together, these results
      suggest that children's propensity to help is systematically related to their
      physiological arousal after they witness others needing help. This sheds new
      light on the biological mechanisms underlying not only young children's social
      perception but also their prosocial motivation more generally.

PMID- 29030229
TI  - Elevation of Proenkephalin 143-183 in Cerebrospinal Fluid in Moyamoya Disease.
AB  - BACKGROUND: In moyamoya disease (MMD), the causes of differences in clinical
      features between children and adults and of the dramatic temporal changes in
      moyamoya vessels are poorly understood. We previously discovered elevated levels
      of m/z 4588 and m/z 4473 peptides in cerebrospinal fluid (CSF) in patients with
      MMD. This study examined the amino acid sequences of these peptides and
      quantified in specimens. METHODS: The m/z 4588 and m/z 4473 peptides in CSF from
      patients with MMD were purified and concentrated by high-performance liquid
      chromatography and ultrafiltration. Liquid chromatography coupled with tandem
      mass spectrometry analysis was performed to identify the amino acid sequences of
      these peptides. We quantified these peptides in samples using sandwich enzyme
      linked immunosorbent assay, and concentrations in CSF were compared between MMD
      (n = 40, 19 male; median age, 37 years) and non-MMD intracranial disease (n = 40,
      19 male; median age, 39 years) as controls. RESULTS: These peptides were
      identified as proenkephalin 143-183 (PENK 143-183). The concentration of PENK 143
      183 was significantly greater in patients with MMD (median, 8,270 pmol/L) than
      control patients (median, 3,760 pmol/L; P < 0.001) and decreased in an age
      dependent manner in MMD (r = -0.57; P < 0.001). The area under the receiver
      operating characteristic curve in children (age <18 years) was 0.885 (95%
      confidence interval 0.741-1). The correlation between proenkephalin concentration
      and temporal changes in moyamoya vessels was suggested. CONCLUSIONS:
      Proenkephalin 143-183 in CSF may offer a helpful diagnostic biomarker in
      pediatric MMD. The effect of enkephalin peptides through opioid growth factor
      receptor or delta opioid receptor might be associated with the pathophysiology of
      MMD.

PMID- 29030230
TI  - Unilateral C1 Sagittal Split Fractures: An Unusual Entity Revisited.
AB  - BACKGROUND: An isolated, unilateral fracture of the C1 lateral mass is a rare
      condition that has been only minimally described in the literature. Historically,
      these fractures have predominantly been managed conservatively with either
      external immobilization or traction. CASE DESCRIPTION: We review the literature
      and present 2 patients that presented after failing conservative management, but
      demonstrated excellent clinical outcomes after surgical treatment. CONCLUSIONS:
      After failure of conservative management, unilateral sagittal split fractures may
      be safely and effectively managed with unilateral open reduction and placement of
      a lag screw.

PMID- 29030232
TI  - A novel bone targeting delivery system carrying phytomolecule icaritin for
      prevention of steroid-associated osteonecrosis in rats.
AB  - One of the effective strategies for prevention of steroid-associated
      osteonecrosis (SAON) is to inhibit bone resorption and fat formation and promote
      bone formation at osteonecrotic sensitive skeletal sites. We identified a novel
      phytomolecule that showed positive effects on osteogenesis, anti-bone resorption
      and anti-adipogenesis in vitro and also developed a bone-targeting delivery
      system (BTDS) for in vivo experimental study. The study investigated if our
      innovative synthesized BTDS carrying this phytomolecule would be able to
      effectively prevent SAON in a rat model. SAON was induced by combined injections
      of lipopolysaccharide and methylprednisolone. SAON rats were divided into four
      groups, one SAON untreated control group and three SAON treatment groups with
      different types of delivery systems (Asp8-liposome-icaritin, liposome-icaritin
      and Asp8-liposome) for two weeks. SAON lesions were identified and osteoclasts
      activity, osteogenesis and adipogenesis at these sites were evaluated by
      immunohistochemistry. Ex vitro study was also designed to evaluate the osteogenic
      and adipogenic potential of the isolated bone marrow stromal cells (BMSCs) via
      real-time PCR and histochemical staining. Our results showed that as a bone
      surface-specific BTDS, Asp8-liposome-icaritin effectively prevented steroids
      treated rats from SAON with significantly decreased osteocytes apoptosis, down
      regulated osteoclatsogenesis and up-regulated osteogenesis. However, both
      liposome-icaritin and Asp8-liposome treatment did not show significant efficacy
      for SAON prevention. In summary, this proof-concept-study showed for the first
      time that the innovative Asp8-liposome-icaritin BTDS was effective for prevention
      of SAON in terms of bone resorption prevention, adipogenesis suppression, and
      bone-formation enhancement.

PMID- 29030233
TI  - Percutaneous left atrial appendage closure is not ready for routine clinical use.

PMID- 29030231
TI  - ALS-associated mutation SOD1G93A leads to abnormal mitochondrial dynamics in
      osteocytes.
AB  - While the death of motor neuron is a pathological hallmark of amyotrophic lateral
      sclerosis (ALS), defects in other cell types or organs may also actively
      contribute to ALS disease progression. ALS patients experience progressive
      skeletal muscle wasting that may not only exacerbate neuronal degeneration, but
      likely has a significant impact on bone function. In our previous published
      study, we have discovered severe bone loss in an ALS mouse model with
      overexpression of ALS-associated mutation SOD1G93A (G93A). Here we further
      provide a mechanistic understanding of the bone loss in ALS animal and cellular
      models. Combining mitochondrial fluorescent indicators and confocal live cell
      imaging, we discovered abnormalities in mitochondrial network and dynamics in
      primary osteocytes derived from the same ALS mouse model G93A. Those
      mitochondrial defects occur in ALS mice after the onset of neuromuscular
      symptoms, indicating that mitochondria in bone cells respond to muscle atrophy
      during ALS disease progression. To examine whether ALS mutation has a direct
      contribution to mitochondrial dysfunction independent of muscle atrophy, we
      evaluated mitochondrial morphology and motility in cultured osteocytes (MLO-Y4)
      with overexpression of mitochondrial targeted SOD1G93A. Compared with osteocytes
      overexpressing the wild type SOD1 as a control, the SOD1G93A osteocytes showed
      similar defects in mitochondrial network and dynamic as that of the primary
      osteocytes derived from the ALS mouse model. In addition, we further discovered
      that overexpression of SOD1G93A enhanced the expression level of dynamin-related
      protein 1 (Drp1), a key protein promoting mitochondrial fission activity, and
      reduced the expression level of optic atrophy protein 1 (OPA1), a key protein
      related to mitochondrial fusion. A specific mitochondrial fission inhibitor
      (Mdivi-1) partially reversed the effect of SOD1G93A on mitochondrial network and
      dynamics, indicating that SOD1G93A likely promotes mitochondrial fission, but
      suppresses the fusion activity. Our data provide the first evidence that
      mitochondria show abnormality in osteocytes derived from an ALS mouse model. The
      accumulation of mutant SOD1G93A protein inside mitochondria directly causes
      dysfunction in mitochondrial dynamics in cultured MLO-Y4 osteocytes. In addition,
      the ALS mutation SOD1G93A-mediated dysfunction in mitochondrial dynamics is
      associated with an enhanced apoptosis in osteocytes, which could be a potential
      mechanism underlying the bone loss during ALS progression.

PMID- 29030234
TI  - Left atrial appendage closure devices: A reasonable therapeutic alternative.

PMID- 29030235
TI  - Impact of ventricular tachycardia ablation on health care utilization.
AB  - BACKGROUND: Catheter ablation of ventricular tachycardia (VT) has been shown to
      reduce the number of recurrent shocks in patients with an implantable
      cardioverter-defibrillator (ICD). However, how VT ablation affects postprocedural
      medical and pharmaceutical usage remains unclear. OBJECTIVE: The purpose of this
      study was to investigate changes in health care resource utilization (HCRU) after
      VT ablation. METHODS: This large-scale, real-world, retrospective study used the
      MarketScan databases to identify patients in the United States with an ICD or
      cardiac resynchronization therapy-defibrillator (CRT-D) undergoing VT ablation.
      We calculated cumulative medical and pharmaceutical expenditures, office visits,
      hospitalizations, and emergency room (ER) visits in the 1-year periods before and
      after ablation. RESULTS: A total of 523 patients met the study inclusion
      criteria. After VT ablation, median annual cardiac rhythm-related medical
      expenditures decreased by $5,408. Moreover, the percentage of patients with at
      least 1 cardiac rhythm-related hospitalization and ER visit decreased from 53%
      and 41% before ablation to 28% and 26% after ablation, respectively. Similar
      changes were observed in the number of all-cause hospitalizations and ER visits,
      but there were no significant changes in all-cause medical expenditures. During
      the year before VT ablation, there was an increasing rate of health care resource
      utilization, followed by drastic slowing after ablation. CONCLUSION: This
      retrospective study demonstrated that catheter ablation seems to reduce
      hospitalization and overall health care utilization in VT patients with an ICD or
      CRT-D in place.

PMID- 29030237
TI  - Contact force sensing for ablation of persistent atrial fibrillation: A
      randomized, multicenter trial.
AB  - BACKGROUND: Impact of contact force sensing (CFS) on ablation of persistent
      atrial fibrillation (PeAF) is unknown. OBJECTIVE: The purpose of the TOUCH AF
      (Therapeutic Outcomes Using Contact force Handling during Ablation of Persistent
      Atrial Fibrillation) randomized trial was to compare CFS-guided ablation to a CFS
      blinded strategy. METHODS: Patients (n = 128) undergoing first-time ablation for
      persistent AF were randomized to a CFS-guided vs CFS-blinded strategy. In the CFS
      guided procedure, operators visualized real-time force data. In the blinded
      procedure, force data were hidden. Wide antral pulmonary vein isolation plus a
      roof line were performed. Patients were followed at 3, 6, 9, and 12 months with
      clinical visit, ECG, and 48-hour Holter monitoring. The primary endpoint was
      cumulative radiofrequency (RF) time for all procedures. Atrial arrhythmia >30
      seconds after 3 months was a recurrence. RESULTS: PeAF was continuous for 26
      weeks (interquartile range [IQR] 13-52), and left atrial size was 45 +/- 5 mm.
      Force in the CFS-blinded and CFS-guided arms was 12 g [IQR 6-20] and 14 g [IQR 9
      20] (P = .10), respectively. Total RF time did not differ between CFS-guided and
      CFS-blinded groups (49 +/- 14 min vs 50 +/- 20 min, respectively; P = .70).
      Single procedure freedom from atrial arrhythmia was 60% in the CFS-guided arm and
      63% in the CFS-blinded arm off drugs. Lesions with gaps were associated with
      significantly less force (11.4 g [IQR 6-19] vs 13.2 g [IQR 8-20], respectively; P
      = .0007) and less force-time integral (174 gs [IQR 91-330] vs 210 gs [IQR 113
      388], respectively; P <.001). CONCLUSION: CFS-guided ablation resulted in no
      difference to RF time or 12-month outcome. Lower force/force-time integral was
      associated with significantly more gaps.

PMID- 29030236
TI  - Accentuated vagal antagonism paradoxically increases ryanodine receptor calcium
      leak in long-term exercised Calsequestrin2 knockout mice.
AB  - BACKGROUND: Long-term aerobic exercise alters autonomic balance, which may not be
      favorable in heart rate (HR)-dependent arrhythmic diseases including
      catecholaminergic polymorphic ventricular tachycardia (CPVT) because of
      preexisting bradycardia and increased sensitivity to parasympathetic stimulation.
      OBJECTIVE: The purpose of this study was to determine whether long-term exercise
      induced autonomic adaptations modify CPVT susceptibility. METHODS: We determined
      exercise-induced parasympathetic effects on HR, arrhythmia incidence, and
      intracellular sarcoplasmic reticulum (SR) Ca2+ leak in atrial (ACM) and
      ventricular (VCM) cardiomyocytes, in exercised (EX) calsequestrin knockout (CASQ2
      /-) mice, a model of CPVT. RESULTS: Although 8-week treadmill running improved
      exercise capacity in EX CPVT mice, the incidence and duration of ventricular
      tachycardia also increased. HR variability analyses revealed an increased high
      frequency component of the power spectrum and root mean square of successive
      differences in R-R intervals indicating accentuated vagal antagonism during beta
      adrenergic stimulation resulting in negligible HR acceleration. In EX CASQ2-/-
      VCM, peak amplitude of Ca2+ transient (CaT) increased, whereas SR Ca2+ content
      decreased. Aberrant Ca2+ sparks occurred at baseline, which was exacerbated with
      isoproterenol. Notably, although 10 MUM of the cholinergic agonist carbachol
      prevented isoproterenol-induced Ca2+ waves in ACM, CaT amplitude, SR Ca2+ load,
      and isoproterenol-induced Ca2+ waves paradoxically increased in VCM. In parallel,
      ventricular ryanodine receptor (RyR2) protein expression increased, whereas
      protein kinase A- and calmodulin-dependent protein kinase II-mediated
      phosphorylation of RyR2 was not significantly altered, which could imply an
      increased number of "leaky" channels. CONCLUSION: Our novel results suggest that
      long-term exercise in CASQ2-/- mice increases susceptibility to ventricular
      arrhythmias by accentuating vagal antagonism during beta-adrenergic challenge,
      which prevents HR acceleration and exacerbates abnormal RyR2 Ca2+ leak in EX
      CASQ2-/- VCM.

PMID- 29030238
TI  - Atrial fibrillation and cognitive decline: Another piece for a big puzzle.

PMID- 29030240
TI  - Postoperative Myocardial Infarction in Administrative Data vs Clinical Registry:
      A Multi-Institutional Study.
AB  - BACKGROUND: Previous studies have documented significant differences between
      administrative data and registry data in the determination of postoperative MI.
      The goal of this study was to characterize discordance between administrative and
      registry data in the determination of postoperative myocardial infarction (MI).
      STUDY DESIGN: This study was performed using data from the American College of
      Surgeons NSQIP merged with administrative data from 8 different hospitals,
      between 2013 and 2015. From each of these sources, the occurrence of a
      postoperative MI, as ascertained by administrative data and NSQIP data, were
      compared. In each situation in which the 2 sources disagreed (discordance), a 2
      clinician chart review was performed to generate a "gold standard" determination
      as to the occurrence of postoperative MI. RESULTS: A total of 43,289 operations
      met our inclusion criteria for analysis. Within this cohort a total of 230 cases
      of MI were identified by administrative data and/or NSQIP data (administrative
      rate 0.41%, NSQIP rate 0.42%). A total of 89 discordant ascertainments were
      identified, of which 42 were admin+/NSQIP- and 47 were admin-/NSQIP+. Accuracy
      (99.9% for both) and concordance (kappa = 0.89 [95% CI 0.86 to 0.92] for
      administrative data, kappa = 0.87 [95% CI 0.84 to 0.91] for NSQIP data) of the 2
      systems were similar when compared against our gold standard (chart review). The
      majority of errors were related to false negatives, with sensitivity rates of 81%
      in both data sources. CONCLUSIONS: In this multi-institutional study,
      administrative data and NSQIP demonstrated a similar ability to determine the
      occurrence of postoperative MI. These findings do not demonstrate an advantage of
      registry data over administrative data in the determination of postoperative MI.

PMID- 29030239
TI  - Surgical Antibiotic Prophylaxis and Risk for Postoperative Antibiotic-Resistant
      Infections.
AB  - BACKGROUND: Antibiotic-resistant infections have high rates of morbidity and
      mortality, and exposure to antibiotics is the crucial risk factor for development
      of antibiotic resistance. If surgical antibiotic prophylaxis (SAP) increases risk
      for antibiotic-resistant infections, prophylaxis may cause net harm, even if it
      decreases overall infection rates. STUDY DESIGN: This retrospective cohort study
      included adults who underwent elective surgical procedures and developed
      infections within 30 postoperative days. Procedures from multiple disciplines
      were included if SAP was considered discretionary by current guidelines.
      Postoperative antibiotic-resistant infections were defined as positive culture
      results from any site within 30 postoperative days, showing intermediate or
      nonsusceptibility across 1 or more antibiotic classes. Surgical antibiotic
      prophylaxis included use of antibiotics within any class and at any dose from 1
      hour before first incision until the end of the operation. RESULTS: Among 689
      adults with postoperative infections, 338 (49%) had postoperative resistant
      infections. Use of SAP was not associated with postoperative antibiotic-resistant
      infections (odds ratio [OR] 0.99; 95% CI 0.67 to 1.46). This result remained
      robust when the SAP definition was extended to antibiotics given within 4 hours
      before first incision (OR 0.94; 95% CI 0.63 to 1.40) and when the follow-up
      window was narrowed to 14 days (OR 0.82; 95% CI 0.50 to 1.34). Previous
      antibiotic-resistant infections were associated with risk for postoperative
      antibiotic-resistant infections (OR 1.81; 95% CI 1.16 to 2.83). CONCLUSIONS: Use
      of SAP was not associated with risk for postoperative antibiotic-resistant
      infections in a large cohort of patients with postoperative infections. This
      provides important reassurance regarding use of surgical antibiotic prophylaxis.

PMID- 29030241
TI  - Discovery of hidden allosteric sites as novel targets for allosteric drug design.
AB  - Hidden allosteric sites, as a novel type of allosteric site, are invisible in
      ligand-unbound (apo) crystal structures, but can emerge in ligand-bound (holo)
      crystal structures when a specific ligand binds to, and stabilizes, a unique
      conformation favored by the ligand. However, the identification of these sites is
      a significant challenge. Several computational and experimental approaches have
      been developed to identify such sites in proteins. Here, we outline these
      approaches, with a focus on examples of the successful use of such techniques.
      The discovery of hidden allosteric sites offers a new avenue for facilitating
      drug design by greatly expanding the repertoire of available drug targets,
      contributing to the search for allosteric drugs for the treatment of human
      diseases.

PMID- 29030242
TI  - Orodispersible dosage forms: biopharmaceutical improvements and regulatory
      requirements.
AB  - Orodispersible dosage forms have a growing presence in the pharmaceutical market
      because their administration can improve the bioavailability of some drugs and
      their prescription can ameliorate patient adherence and/or compliance. Here, we
      review the main features of orodispersible tablets, including oral lyophilisates,
      and orodispersible films along with their main production technologies. We
      summarize the bioavailability data and critically discussed their potential to
      improve patient adherence and/or compliance. We revisit this information in light
      of both the European Union (EU) and US regulatory frameworks, focusing on the
      differences in the definitions of such dosage forms and the requirements for
      marketing authorization.

PMID- 29030244
TI  - Pore formation and the key factors in antibacterial activity of aurein 1.2 and
      LLAA inside lipid bilayers, a molecular dynamics study.
AB  - Aurein 1.2 and LLAA are two antimicrobial peptides with different antibacterial
      activities (LLAA>Aurein 1.2), though their amino acid sequences are similar. In
      this manuscript, we study the key features for the different antibacterial
      activities of these peptides using molecular dynamics simulation. We find that in
      water, both peptides become disordered and LLAA is observed to have higher water
      solubility, a feature which may contribute to enhancing its propensity to disrupt
      the bilayer and thus higher activity. Both peptides are also investigated while
      they are initially located inside lipid bilayer as a pre-formed vertical channel
      composed of five parallel copies of each peptide. LLAA demonstrates larger
      structural deviation from the initial helical structure and also more structural
      flexibility which is concluded to be a key feature in its stronger activity. In
      the presence of LLAA, the bilayer order is perturbed more pronouncedly and the
      number of water molecules penetrating into bilayer is higher. It is shown that
      stronger electrostatic interactions, more hydrophobic contacts and more hydrogen
      bonds between lipid and LLAA also lead to stronger activity of LLAA. The
      simulation results show instability of the barrel-stave pores for our peptides
      inside lipid bilayers.

PMID- 29030245
TI  - Effect of phosphatidylcholine bilayer thickness and molecular order on the
      binding of the antimicrobial peptide maculatin 1.1.
AB  - Antimicrobial peptides (AMPs) interact directly with bacterial membrane lipids.
      Thus, changes in the lipid composition of bacterial membranes can have profound
      effects on the activity of AMPs. In order to understand the effect of bilayer
      thickness and molecular order on the activity of AMPs, the interaction of
      maculatin 1.1 (Mac1.1) with phosphatidylcholine (PC) model membranes composed of
      different monounsaturated acyl chain lengths between 14 and 22 carbons was
      characterised by dual polarisation interferometry (DPI) and 31P and 1H solid
      state NMR techniques. The thickness and bilayer order of each PC bilayer showed a
      linear dependence on the acyl chain length. The binding of Mac1.1 exhibited a
      biphasic dependency between the amount of bound Mac1.1 and bilayer thickness,
      whereby the mass of bound peptide increased from C14 to C16 and then decreased
      from C16 to C22. Significant perturbation of 31P chemical shift anisotropy (CSA)
      values was only observed for DOPC (C18) and DEPC (C22), respectively. In the case
      of DEPC, the greater range in CSA indicated different headgroup conformations or
      environments in the presence of Mac1.1. Overall, the results indicated that there
      is a significant change in the bilayer order upon binding of Mac1.1 and this
      change occurred in a co-operative manner at higher concentrations of Mac1.1 with
      increasing bilayer thickness and order. Overall, an optimum bilayer thickness and
      lipid order may be required for effective membrane perturbation by Mac1.1 and
      increasing the bilayer thickness and order may counteract the activity of Mac1.1
      and play a role in antimicrobial resistance to AMPs.

PMID- 29030243
TI  - The inhibition of the kynurenine pathway prevents behavioral disturbances and
      oxidative stress in the brain of adult rats subjected to an animal model of
      schizophrenia.
AB  - Evidence has shown that the kynurenine pathway (KP) plays a role in the onset of
      oxidative stress and also in the pathophysiology of schizophrenia. The aim of
      this study was to use a pharmacological animal model of schizophrenia induced by
      ketamine to investigate if KP inhibitors could protect the brains of Wistar rats
      against oxidative stress and behavioral changes. Ketamine, injected at the dose
      of 25mg/kg, increased spontaneous locomotor activity. However, the inhibitors of
      tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase (IDO) and
      kynurenine-3-monooxygenase (KMO) were able to reverse these changes. In addition,
      the IDO inhibitor prevented lipid peroxidation, and decreased the levels of
      protein carbonyl in the prefrontal cortex (PFC), hippocampus and striatum. It
      also increased the activity of superoxide dismutase (SOD) in the hippocampus, as
      well as increasing the levels of catalase activity in the PFC and hippocampus.
      The TDO inhibitor prevented lipid damage in the striatum and reduced the levels
      of protein carbonyl in the hippocampus and striatum. Also, the TDO inhibitor
      increased the levels of SOD activity in the striatum and CAT activity in the
      hippocampus of ketamine-induced pro-oxidant effects. Lipid damage was not
      reversed by the KMO inhibitor. The KMO inhibitor increased the levels of SOD
      activity in the hippocampus, and reduced the levels of protein carbonyl while
      elevating the levels of CAT activity in the striatum of rats that had been
      injected with ketamine. Our findings revealed that the KP pathway could be a
      potential mechanism by which a schizophrenia animal model induced by ketamine
      could cause interference by producing behavioral disturbance and inducing
      oxidative stress in the brain, suggesting that the inhibition of the KP pathway
      could be a potential target in treating schizophrenia.

PMID- 29030246
TI  - Interaction of a model apolipoprotein, apoLp-III, with an oil-phospholipid
      interface.
AB  - Lipid droplets are "small" organelles that play an important role in de novo
      synthesis of new membrane, and steroid hormones, as well as in energy storage.
      The way proteins interact specifically with the oil-(phospho-)lipid monolayer
      interface of lipid droplets is a relatively unexplored but crucial question.
      Here, we use our home built liquid droplet tensiometer to mimic intracellular
      lipid droplets and study protein-lipid interactions at this interface. As model
      neutral lipid binding protein, we use apoLp-III, an amphipathic alpha-helix
      bundle protein. This domain is also found in proteins from the perilipin family
      and in apoE. Protein binding to the monolayer is studied by the decrease in the
      oil/water surface tension. Previous work used POPC (one of the major lipids found
      on lipid droplets) to form the phospholipid monolayer on the triolein surface.
      Here we expand this work by incorporating other lipids with different physico
      chemical properties to study the effect of charge and lipid head-group size. This
      study sheds light on the affinity of this important protein domain to interact
      with lipids.

PMID- 29030249
TI  - Sex as a biological variable: Drug use and abuse.
AB  - The study of sex as a biological variable is a necessary emphasis across a wide
      array of endpoints, including basic neuroscience, medicine, mental health,
      physiology and behavior. The present review summarizes work from clinical and
      preclinical populations on sex differences in drug use and abuse, ranging from
      initiation to escalation/dysregulation and from drug cessation/abstinence to
      relapse. These differences are analyzed in the context of the addiction cycle
      conceptualization of Koob and his colleagues and address patterns of drug use
      (binge/intoxication), motivation underlying its use (withdrawal/negative affect)
      and likelihood and causes of craving and relapse of drug taking
      (preoccupation/anticipation). Following this overview, an assessment of the basis
      for the reported sex differences is discussed in the context of the affective
      (rewarding and aversive) properties of drugs of abuse and how such properties and
      their balance vary with sex and contribute to drug intake. Finally, the
      interaction of sex with several experiential (drug history) and subject (age)
      factors and how these interactions affect reward and aversion are discussed to
      highlight the importance of understanding such interactions in predicting drug
      use and abuse. We note that sex as a biological variable remains one of critical
      evaluation and that such investigations of sex differences in drug use and abuse
      continue and be expanded to assess all facets of their mediation, including these
      affective properties, how their balance may be impacted by the multiple
      conditions under which drugs are taken and how this overall balance affects drug
      use and addiction vulnerability.

PMID- 29030248
TI  - Explicit wanting and liking for palatable snacks are differentially affected by
      change in physiological state, and differentially related to salivation and
      hunger.
AB  - Incentive salience theory (IST) suggests that 'wanting' and liking are
      dissociable processes. We argue that explicit measures of wanting in humans can
      reflect the impact of implicit 'wanting' as envisaged by IST, suggesting that
      dissociations should also be evident for explicit judgments of wanting and
      liking. To test this, participants were asked to make ratings of these variables
      for 8 palatable snack foods - and in a related test salivation rate was also
      assessed. Participants viewed and sniffed each snack food and rated wanting, and
      then sampled it and rated liking and whether they wanted more of it. Following a
      lunch eaten to satiety, and composed in part of half of the palatable snack
      foods, participants repeated their evaluations of the snack foods (and salivation
      rate). Liking changed less across lunch than wanting and want more ratings, the
      last-mentioned changing the most. Change in liking was associated with change in
      salivation rate, independent of wanting, and change in wanting was associated
      with change in hunger independent of liking. We argue these dissociations are
      consistent with 'wanting' influencing explicit wanting, and that want more
      ratings may represent a 'purer' measure of IST 'wanting'.

PMID- 29030247
TI  - Inhibition of intestinal ascorbic acid uptake by lipopolysaccharide is mediated
      via transcriptional mechanisms.
AB  - Ascorbic acid (AA) accumulation in intestinal epithelial cells is an active
      transport process mainly mediated by two sodium-dependent vitamin C transporters
      (SVCT-1 and SVCT-2). To date, little is known about the effect of gut microbiota
      generated lipopolysaccharide (LPS) on intestinal absorption of water-soluble
      vitamins. Therefore, the objective of this study was to investigate the effects
      of bacterially-derived LPS on AA homeostasis in enterocytes using Caco-2 cells,
      mouse intestine and intestinal enteroids models. Pre-treating Caco-2 cells and
      mice with LPS led to a significant decrease in carrier-mediated AA uptake. This
      inhibition was associated with a significant reduction in SVCT-1 and SVCT-2
      protein, mRNA, and hnRNA expression. Furthermore, pre-treating enteroids with LPS
      also led to a marked decrease in SVCT-1 and SVCT-2 protein and mRNA expression.
      Inhibition of SVCT-1 and SVCT-2 occurred at least in part at the transcriptional
      level as promoter activity of SLC23A1 and SLC23A2 was attenuated following LPS
      treatment. Subsequently, we examined the protein and mRNA expression levels of
      HNF1alpha and Sp1 transcription factors, which are needed for basal SLC23A1 and
      SLC23A2 promoter activity, and found that they were significantly decreased in
      the LPS treated Caco-2 cells and mouse jejunum; this was reflected on level of
      the observed reduction in the interaction of these transcription factors with
      their respective promoters in Caco-2 cells treated with LPS. Our findings
      indicate that LPS inhibits intestinal carrier- mediated AA uptake by down
      regulating the expression of both vitamin C transporters and transcriptional
      regulation of SLC23A1 and SLC23A2 genes.

PMID- 29030250
TI  - Fructo-oligosaccharides reduce energy intake but do not affect adiposity in rats
      fed a low-fat diet but increase energy intake and reduce fat mass in rats fed a
      high-fat diet.
AB  - The ingestion of low or high lipid diets enriched with fructo-oligosaccharide
      (FOS) affects energy homeostasis. Ingesting protein diets also induces a
      depression of energy intake and decreases body weight. The goal of this study was
      to investigate the ability of FOS, combined or not with a high level of protein
      (P), to affect energy intake and body composition when included in diets
      containing different levels of lipids (L). We performed two studies of similar
      design over a period of 5weeks. During the first experiment (exp1), after a 3
      week period of adaptation to a normal protein-low fat diet, the rats received one
      of the following four diets for 5weeks (6 rats per group): (i) normal protein
      (14% P/E (Energy) low fat (10% L/E) diet, (ii) normal protein, low fat diet
      supplemented with 10% FOS, (iii) high protein (55%P/E) low fat diet, and (iv)
      high protein, low fat diet supplemented with 10% FOS. In a second experiment
      (exp2) after the 3-week period of adaptation to a normal protein-high fat diet,
      the rats received one of the following 4 diets for 5weeks (6 rats per group): (i)
      normal protein, high fat diet (35% of fat), (ii) normal protein, high fat diet
      supplemented with 10% FOS, (iii) high protein high fat diet and (iv) high protein
      high fat diet supplemented with 10% FOS. In low-fat fed rats, FOS did not affect
      lean body mass (LBM) and fat mass but the protein level reduced fat mass and
      tended to reduce adiposity. In high-fat fed rats, FOS did not affect LBM but
      reduced fat mass and adiposity. No additive or antagonistic effects between FOS
      and the protein level were observed. FOS reduced energy intake in low-fat fed
      rats, did not affect energy intake in normal-protein high-fat fed rats but
      surprisingly, and significantly, increased energy intake in high-protein high-fat
      fed rats. The results thus showed that FOS added to a high-fat diet reduced body
      fat and body adiposity.

PMID- 29030251
TI  - Intravenous immunoglobulin (IVIG) treatment modulates peripheral blood Th17 and
      regulatory T cells in recurrent miscarriage patients: Non randomized, open-label
      clinical trial.
AB  - BACKGROUND: Th17 cells and Treg cells have been proposed as new risk factors for
      recurrent miscarriage (RM). In this study, we investigated the effect of
      Intravenous immunoglobulin G (IVIG) on the levels and function of Th17 and Treg
      cells and pregnancy outcome in women with RM. MATERIALS AND METHODS: 94 pregnant
      women with RM were enrolled in this study. Blood was drawn at the time of
      positive pregnancy. On the same day, IVIG 400mg/kg was administered intravenously
      for 44 patients. 50 other RM patients were included as no IVIG interfering
      control group. Following the first administration, IVIG was given every 4 weeks
      through 32 weeks of gestation. Peripheral blood was drawn after the last
      administration (32 weeks after pregnancy). RESULTS: IVIG down-regulated Th17
      cells population and function and up-regulated Treg cells population and function
      were significant in the treated group. Pregnancy outcome in IVIG treated subjects
      was successful in 38 out of 44 RM women (86.3%). However, pregnancy outcome was
      successful in 21 out of 50 untreated RM women (42%). CONCLUSION: Administration
      of IVIG in RM women with cellular immune cells abnormalities during pregnancy
      influences Th17/Treg ratio in peripheral blood and enhances Treg and decreases
      Th17 responses.

PMID- 29030252
TI  - Sub-clonal analysis of the murine C1498 acute myeloid leukaemia cell line reveals
      genomic and immunogenic diversity.
AB  - BACKGROUND: In acute myeloid leukaemia (AML)-affected patients, the presence of
      heterogeneous sub-clones at diagnosis has been shown to be responsible for
      minimal residual disease and relapses. The role played by the immune system in
      this leukaemic sub-clonal hierarchy and maintenance remains unknown. As leukaemic
      sub-clone immunogenicity could not be evaluated in human AML xenograft models, we
      assessed the sub-clonal diversity of the murine C1498 AML cell line and the
      immunogenicity of its sub-clones in immune-competent syngeneic mice. METHODOLOGY:
      The murine C1498 cell line was cultured in vitro and sub-clonal cells were
      generated after limiting dilution. The genomic profiles of 6 different sub-clones
      were analysed by comparative genomic hybridization arrays (CGH). The sub-clones
      were then injected into immune-deficient and - competent syngeneic mice. The
      immunogenicities of the sub-clones was evaluated through 1) assessment of mouse
      survival, 2) determination of leukaemic cell infiltration into organs by flow
      cytometry and the expression of a fluorescent reporter gene, 3) assessment of the
      CTL response ex vivo and 4) detection of residual leukaemic cells in the organs
      via amplification of the genomic reporter gene by real-time PCR (qPCR). RESULTS:
      Genomic analyses revealed heterogeneity among the parental cell line and its
      derived sub-clones. When injected individually into immune-deficient mice, all
      sub-clones induced cases of AML with different kinetics. However, when
      administered into immune-competent animals, some sub-clones triggered AML in
      which no mice survived, whereas others elicited reduced lethality rates. The AML
      surviving mice presented efficient anti-leukaemia CTL activity ex vivo and
      eliminated the leukaemic cells in vivo. CONCLUSION: We showed that C1498 cell sub
      clones presented genomic heterogeneity and differential immunogenicity resulting
      either in immune escape or elimination. Such findings could have potent
      implications for new immunotherapeutic strategies in patients with AML.

PMID- 29030253
TI  - Polymorphisms in the TFAM and PGC1-alpha genes and their association with
      polycystic ovary syndrome among South Indian women.
AB  - We investigated the link between polymorphisms in genes involved in mitochondrial
      biogenesis, mitochondrial transcription factor A (TFAM) and Peroxisome
      proliferator activated receptor gamma coactivator-1 alpha (PGC-1alpha) and
      further studied the role of these genes on the pathophysiology of polycystic
      ovary syndrome (PCOS). This case-control study was carried out in 118 PCOS cases
      and 110 controls. In the present study we genotyped three polymorphisms of PGC1
      alpha gene (rs8192678-Gly482Ser, rs13131226 and rs2970856) and polymorphism of
      TFAM gene (rs1937-+35G/C) by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) analysis. In addition, to better understand
      genetic contributions to the pathophysiology of PCOS, mtDNA copy number (MCN) was
      quantified using a qRT-PCR assay in the subjects. The results revealed that the
      distribution of genotypes and allele frequency of the PGC-1alpha Gly482Ser
      polymorphism in PCOS patients was statistically significant from those of the
      control group respectively (OR-2.488; 95% CI-1.0673 to 5.7998; P=0.047), (OR
      1.6091; 95% CI-1.0955 to 2.3634; P=0.015) indicating that the presence of 'A'
      allele might confer risk to PCOS. Patients with the 'AA' genotype showed
      significantly lower levels of MCN compared with patients with other genotypes. In
      addition, patients carrying CT genotype of PGC1-alpha rs2970856 demonstrated
      significantly higher levels of LH (P=0.030) than TT and CC genotypes. In
      conclusion, our study indicates that carriers of the PGC-1alpha rs8192678 'Ser'
      allele have increased risk of developing PCOS.

PMID- 29030254
TI  - Complete structure and variation of the chloroplast genome of Agropyron cristatum
      (L.) Gaertn.
AB  - Agropyron cristatum (L.) Gaertner, a perennial grass in the tribe Triticeae
      (Poaceae), is a wild relative of cereal crops that is suitable for genetic
      improvement. In this study, we first sequenced the complete chloroplast (cp)
      genome of Ag. cristatum using Hiseq4000 PE150. The Ag. cristatum chloroplast
      genome is 135,554bp in length, has a typical quadripartite structure and contains
      76 protein-coding genes, 29 tRNA genes and four rRNA genes. The cp genome of Ag.
      cristatum was used for comparison with other seven Triticeae species. One large
      variable region (800bp), which primarily contained the rpl23 (non-reciprocally
      translocated from IRs) and accD genes, was detected between rbcL gene and psaI
      gene within LSC region. The deletion of the accD and translocated rpl23 genes in
      Ag. cristatum indicated an independent gene-loss events or an additional
      divergence in Triticeae. Analyses of the dn/ds ratio and K2-P's genetic distance
      for 76 protein-coding genes showed that genes with evolutionary divergence might
      suffer from the effect of sequence regional constraints or gene functional
      constraints in Triticeae species. Our research will generally contribute to the
      knowledge of plastid genome evolution in Triticeae.

PMID- 29030255
TI  - Molecular cloning and characterization of secretory carbonic anhydrase VI in
      pufferfish (Takifugu rubripes).
AB  - Carbonic anhydrase VI (CA VI) has been characterized as a secretory isozyme in
      mammals. Our present study confirmed the occurrence of CA VI in pufferfish
      (Takifugu rubripes). In this study, genomic sequence information for the CA VI of
      pufferfish was used for molecular cloning. We cloned a 1821 bp cDNA sequence,
      which consisted of a complete coding sequence of 1623bp and a deduced amino acid
      sequence of 540 amino acids from the open reading frame. A BLAST search indicated
      that this protein exhibits 53%, 79%, and 67% identity with human, tilapia, and
      gar CA VI, respectively. It also shows 63%-77% identity with other fish CA VI
      like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
      Moreover, alignment of two or more sequences revealed that the protein sequence
      of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
      An NH2-terminal signal peptide of 18 amino acids in length was predicted in the
      pufferfish CA VI sequence. Three potential N-linked glycosylation sites and two
      cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond
      were present in pufferfish CA VI. In silico and phylogenetic analyses revealed
      that pufferfish CA VI is an extracellular secretory protein. Active site analysis
      indicated that this protein is a low-activity CA isozymes due to a characteristic
      Val/Ile substitution at position 207. Homology modeling of puffer CA VI was
      performed using the crystal structure of human carbonic anhydrase XIV as a
      template structure, based on high similarity. Reverse transcription-polymerase
      chain reaction (PCR), quantitative PCR and in situ hybridization results revealed
      that, the pufferfish CA VI is highly expressed in liver tissue.

PMID- 29030256
TI  - Ficus virens proanthocyanidins induced apoptosis in breast cancer cells
      concomitantly ameliorated 5-fluorouracil induced intestinal mucositis in rats.
AB  - 5-Fluorouracil (5-FU) is a commonly used chemotherapeutic agent for breast
      cancer. However, its use often leads to drug resistance and mucositis. This study
      aimed to investigate whether proanthocyanidins from Ficus virens possessed anti
      breast cancer and anti-mucositis activities. The results showed that the
      cytotoxic effects of the proanthocyanidins against MDA-MB-231 and MCF-7 breast
      cancer cells were in the order of stem barks proanthocyanidins (SPAs) > leaves
      proanthocyanidins > fruits proanthocyanidins. Moreover, SPAs induced apoptosis in
      both cell lines which were accompanied with an increase in loss of mitochondrial
      membrane potential, production of reactive oxygen species, Bax to Bcl-2 protein
      expression ratio, and activated caspase 3. Furthermore, intraperitoneal injection
      of 5-FU (150 mg/kg body weight) resulted in body weight loss and jejunal injury
      in the rats while administration of SPAs (100 mg/kg body weight) counteracted
      these changes. Collectively, our study demonstrated that SPAs induced apoptosis
      cell death in breast cancer cells while ameliorating the symptoms of intestinal
      mucositis in rats.Therefore, SPAs merits further exploration as a potential
      therapeutic agent for breast cancer and chemotherapy-induced mucositis.

PMID- 29030257
TI  - RIFM fragrance ingredient safety assessment, 2-pentylcyclopentan-1-one, CAS
      Registry Number 4819-67-4.

PMID- 29030258
TI  - RIFM fragrance ingredient safety assessment, menthyl acetate (isomer
      unspecified), CAS Registry Number 16409-45-3.

PMID- 29030259
TI  - RIFM fragrance ingredient safety assessment, dihydro-beta-ionol, cas registry
      number 3293-47-8.

PMID- 29030260
TI  - Cyanidin-3-O-glucoside promotes the biosynthesis of progesterone through the
      protection of mitochondrial function in Pb-exposed rat leydig cells.
AB  - Cyanidin-3-O-glucoside (C3G) is an anthocyanin that has been reported to reduce
      the toxicity of heavy metals. In the present study, the protection effects of C3G
      on the biosynthesis of progesterone, the precursor of testosterone, against lead
      (Pb) in R2C rat Leydig cells were examined. Treatment of R2C cells with 100 MUM
      Pb resulted in a significant decrease in progesterone production. After being
      cultured in a medium containing C3G and Pb, R2C cells exhibited an increase in
      progesterone concentration compared with the Pb treatment, as a result of up
      regulation of the expression of the steroidogenic enzymes steroidogenic acute
      regulatory protein (StAR), 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and
      cytochrome P450 enzyme cholesterol side chain cleavage enzyme (CYP11A1). Pb
      induced inhibition of extracellular regulated Kinase 1/2 (ERK 1/2)
      phosphorylation and down-regulation of protein kinase A (PKA) expression were
      alleviated by C3G. In addition, Pb-induced reactive oxygen species (ROS)
      overproduction led to mitochondrial depolarization, resulting in a decrease in
      progesterone biosynthesis, while C3G intervention reduced the ROS level and
      increased progesterone production. In conclusion, C3G may alleviate the Pb
      induced decrease of progesterone biosynthesis by modulating the dysfunction of
      mitochondria, including decreasing oxidative stress and regulating expression of
      steroidogenic enzyme proteins.

PMID- 29030261
TI  - RIFM fragrance ingredient safety assessment, alpha-Isobutylphenethyl alcohol, CAS
      Registry Number 7779-78-4.

PMID- 29030262
TI  - Combining actigraphy, ecological momentary assessment and neuroimaging to study
      apathy in patients with schizophrenia.
AB  - BACKGROUND: Apathy can be defined as a reduction of goal-directed behavior and is
      a strong predictor for poor functional outcome in schizophrenia. However, no
      objective measure of apathy has been identified and assessment is limited to
      retrospective interview-based ratings. Here we aimed to identify more precise
      objective readouts of apathy for translational research and clinical practice.
      METHODS: We employed a combined approach including interview-based ratings of the
      two negative symptom factors apathy and diminished expression, actigraphy based
      measures of spontaneous motor activity and the evaluation of daily activities
      using ecological momentary assessment. Furthermore, a functional magnetic
      resonance imaging task for reward anticipation was applied to investigate shared
      and divergent neural correlates of interview-based and behaviorally measured
      apathy. RESULTS: We found in 18 schizophrenia patients with high interview-based
      apathy levels that motor activity was negatively correlated with apathy but not
      with diminished expression. In contrast, measures of daily activities were not
      associated with apathy. Neural activation during reward anticipation revealed an
      association between hypoactivation of the ventral striatum and interview-based
      apathy as well as hypoactivation of the inferior frontal gyrus and motor activity
      level. CONCLUSIONS: Spontaneous motor activity is an objective readout of apathy,
      which was specific and not present for diminished expression. On a neural level,
      interview-based and objective measures of apathy showed divergent neural
      correlates in the cortical-striatal network, which suggests dissociable neural
      processes. Finally, motor activity provides a promising readout for quantifying
      apathy in both translational research and clinical practice.

PMID- 29030263
TI  - The role of endemic plants in Mauritian traditional medicine - Potential
      therapeutic benefits or placebo effect?
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The Mauritian endemic flora has been recorded to
      be used as medicines for nearly 300 years. Despite acceptance of these endemic
      plants among the local population, proper documentation of their therapeutic uses
      is scarce. This review aims at summarising documented traditional uses of
      Mauritian endemic species with existing scientific data of their alleged
      bioactivities, in a view to appeal for more stringent validations for their
      ethnomedicinal uses. MATERIAL AND METHODS: A comprehensive bibliographic
      investigation was carried out by analysing published books on ethnopharmacology
      and international peer-reviewed papers via scientific databases namely
      ScienceDirect and PubMed. The keywords "Mauritius endemic plants" and "Mauritius
      endemic medicinal plants" were used and articles published from 1980 to 2016 were
      considered. 675 works of which 12 articles were filtered which documented the
      ethnomedicinal uses and 22 articles reported the biological activities of
      Mauritian endemic plants. Only materials published in English or French language
      were included in the review. Available data on the usage of Mauritian endemic
      plants in traditional medicine and scientific investigation were related. RESULTS
      AND DISCUSSION: We documented 87 taxa of Mauritian endemic plants for their
      medicinal value. Endemic plants are either used as part of complex herbal
      formulations or singly, and are prescribed by herbalists to mitigate a myriad of
      diseases from metabolic disorders, dermatological pathologies, arthritis to
      sexually transmissible diseases. However, these species have undergone a limited
      consistent evaluation to validate their purported ethnomedicinal claims. As the
      World Health Organization Traditional Medicine Strategy 2014-2023 emphasises on
      moving traditional medicine into mainstream medicine on an equally trusted
      footage, the re-evaluation and modernization of Mauritius cultural heritage
      become necessary. CONCLUSIONS: With a consumer-driven 'return to nature',
      scientific validation and valorization of the herbal remedies, including efficacy
      and safety are, therefore, important. This review reports the scarcity of
      research on validating the efficacy and safety of medicinal endemic plants. This
      calls for the use of optimised methodologies to investigate the claims of
      therapeutic effects resulting from the use of these traditional medicines.

PMID- 29030264
TI  - Exploring the effect of parental influence on children's physical activity: The
      mediating role of children's perceptions of parental support.
AB  - The purpose of this study was to test a conceptual model linking parental support
      and parental physical activity (PA), with children's perception of parental
      support and children's PA. Baseline data were drawn from the Grade 5 ACT-i-Pass
      community-based PA intervention conducted in London, Ontario between May and
      October 2014. Parent and child PA were measured using the International Physical
      Activity Questionnaire and Physical Activity Questionnaire for Children,
      respectively. Questions pertaining to parental support and children's perception
      of that parental support were obtained via questionnaires. We employed structural
      equation modeling techniques to test the conceptual model. In total, 467 boys and
      469 girls were included in the study. The model provided an acceptable model fit.
      Child's perception of parental support for PA had a positive effect on boys'
      (b=0.319) and girls' (b=0.326) PA. Parental PA was not significantly related to
      child's perception of parental support for PA. However, parent reported support
      for PA had a significant, positive effect on child's perception of parental
      support for boys (b=0.352) and girls (b=0.584). In terms of the indirect effects,
      the effect of parental PA on child's PA was not statistically significant;
      however, as expected, parental support for PA had a statistically significant
      indirect effect on child PA level in both groups. The findings of this study
      demonstrate the importance of children's perceptions of parental support in
      relation to their PA behaviours. Developing a better understanding of factors
      related to children's PA and identifying determinants and mediators of activity
      behaviours will help inform PA interventions.

PMID- 29030265
TI  - Associations of active commuting with body fat and visceral adipose tissue: A
      cross-sectional population based study in the UK.
AB  - The promotion of active travel (walking and cycling) is one promising approach to
      prevent the development of obesity and related cardio-metabolic disease. However
      the associations between active travel and adiposity remain uncertain. We used
      the Fenland study (a population based-cohort study; Cambridgeshire, UK, 2005-15)
      to describe the association of commuting means with DEXA measured body fat and
      visceral adipose tissue (VAT) among commuters (aged 29-65years; n=7680). We
      stratified our sample into those living near (within five miles) and far (five
      miles or further) from work, and categorised commuting means differently for each
      group reflecting their different travel options. Associations were adjusted for
      age, education, Mediterranean diet score, smoking, alcohol consumption, test site
      and either self-reported physical activity or objective physical activity. Among
      those living near to work, people who reported regularly cycling to work had
      lower body fat than those who only used the car (adjusting for self-reported
      physical activity: women, -1.74%, 95% CI: -2.27% to -0.76%; men, -1.30%, -2.26%
      to -0.33%). Among those who lived far from work, people who reported regular car
      use with active travel had lower body fat (women; -1.18%, 95% CI: -2.23% to 
      0.13%; men, -1.19%, -1.93% to -0.44%). Findings were similar for VAT and when
      adjusting for objectively measured physical activity instead of self-reported
      physical activity. In conclusion, active commuting may reduce adiposity and help
      prevent related cardio-metabolic disease. If people live too far from work to
      walk or cycle the whole journey, incorporating some active travel within the
      commute is also beneficial.

PMID- 29030266
TI  - Plasmid-mediated doxycycline resistance in a Yersinia pestis strain isolated from
      a rat.
AB  - The emergence of antibiotic-resistant Yersinia pestis strains represents a public
      health concern. Two antibiotic-resistant Y. pestis strains isolated from
      Madagascar have been previously identified and characterised. Both strains
      carried conjugative plasmids that conferred resistance to streptomycin or to
      multiple antibacterial drugs, respectively. Here we characterised a novel Y.
      pestis strain (IP2180H) that exhibited resistance to doxycycline. This strain was
      isolated from a rat in Antananarivo (Madagascar) in 1998. Resistance was carried
      by a conjugative plasmid (pIP2180H) homologous to pB71 from Salmonella enterica.
      The plasmid of the previously identified streptomycin-resistant Y. pestis strain
      was also sequenced and it was found that the three antibiotic resistance Y.
      pestis plasmids sequenced until now are genetically unrelated and are also
      unrelated to multidrug resistance plasmids from the phylogenetically close
      bacterial species Yersinia pseudotuberculosis. The fact that the three antibiotic
      resistant Malagasy Y. pestis strains were isolated from different hosts, at
      different times, from distant locations, and carried unrelated plasmids indicates
      independent horizontal acquisition of genetic material and further demonstrates
      the capacity of Y. pestis to acquire antibiotic resistance plasmids under natural
      conditions. Since these resistance plasmids can frequently carry or easily trap
      antibiotic resistance cassettes, the emergence of new multidrug-resistant Y.
      pestis strains may be expected and would represent a major health threat.

PMID- 29030267
TI  - Effects of pex1 disruption on wood lignin biodegradation, fruiting development
      and the utilization of carbon sources in the white-rot Agaricomycete Pleurotus
      ostreatus and non-wood decaying Coprinopsis cinerea.
AB  - Peroxisomes are well-known organelles that are present in most eukaryotic
      organisms. Mutant phenotypes caused by the malfunction of peroxisomes have been
      shown in many fungi. However, these have never been investigated in
      Agaricomycetes, which include white-rot fungi that degrade wood lignin in nature
      almost exclusively and play an important role in the global carbon cycle. Based
      on the results of a forward genetics study to identify mutations causing defects
      in the ligninolytic activity of the white-rot Agaricomycete Pleurotus ostreatus,
      we report phenotypes of pex1 disruptants in P. ostreatus, which are defective in
      two major features of white-rot Agaricomycetes: lignin biodegradation and
      mushroom formation. Pex1 disruption was also shown to cause defects in the hyphal
      growth of P. ostreatus on certain sawdust and minimum media. We also demonstrated
      that pex1 is essential for fruiting initiation in the non-wood decaying
      Agaricomycete Coprinopsis cinerea. However, unlike P. ostreatus, significant
      defects in hyphal growth on the aforementioned agar medium were not observed in
      C. cinerea. This result, together with previous C. cinerea genetic studies,
      suggests that the regulation mechanisms for the utilization of carbon sources are
      altered during the evolution of Agaricomycetes or Agaricales.

PMID- 29030268
TI  - Topical vancomycin to reduce surgical-site infections in neurosurgery: Study
      protocol for a multi-center, randomized controlled trial.
AB  - Surgical-site infections (SSIs) account for 20% of all healthcare-associated
      infections, are the most common nosocomial infection among surgical patients, and
      are a focus of quality improvement initiatives. Despite implementation of many
      quality care measures (e.g. prophylactic antibiotics), SSIs remain a significant
      cause of morbidity, mortality, and economic burden, particularly in the field of
      neurosurgery. Topical vancomycin is increasingly utilized in instrumented spinal
      and cardiothoracic procedures, where it has been shown to reduce the risk of
      SSIs. However, a randomized controlled trial assessing its efficacy in the
      general neurosurgical population has yet to be done. The principle aim of
      "Topical Vancomycin for Neurosurgery Wound Prophylaxis" (NCT02284126) is to
      determine whether prophylactic, topical vancomycin reduces the risk of SSIs in
      the adult neurosurgical population. This prospective, multicenter, patient
      blinded, randomized controlled trial will enroll patients to receive the standard
      of care plus topical vancomycin, or the standard of care alone. The primary
      endpoint of this study is a SSI by postoperative day (POD) 30. Patients must be
      over 18years of age. Patients are excluded for renal insufficiency, vancomycin
      allergy, and some ineligible procedures. Univariate analysis and logistic
      regression will determine the effect of topical vancomycin on SSIs at 30days. A
      randomized controlled trial is needed to determine the efficacy of this
      treatment. Results of this trial are expected to directly influence the standard
      of care and prevention of SSIs in neurosurgical patients.

PMID- 29030269
TI  - The importance of inclusion of kinetic information in the extrapolation of high
      to-low concentrations for human limit setting.
AB  - Human health risk assessment of inhalation exposures generally includes a high-to
      low concentration extrapolation. Although this is a common step in human risk
      assessment, it introduces various uncertainties. One of these uncertainties is
      related to the toxicokinetics. Many kinetic processes such as absorption,
      metabolism or excretion can be subject to saturation at high concentration
      levels. In the presence of saturable kinetic processes of the parent compound or
      metabolites, disproportionate increases in internal blood or tissue concentration
      relative to the external concentration administered may occur resulting in
      nonlinear kinetics. The present paper critically reviews human health risk
      assessment of inhalation exposure. More specific, it emphasizes the importance of
      kinetic information for the determination of a safe exposure in human risk
      assessment of inhalation exposures assessed by conversion from a high animal
      exposure to a low exposure in humans. For two selected chemicals, i.e. methyl
      tert-butyl ether and 1,2-dichloroethane, PBTK-modelling was used, for
      illustrative purposes, to follow the extrapolation and conversion steps as
      performed in existing risk assessments for these chemicals. Human health-based
      limit values based on an external dose metric without sufficient knowledge on
      kinetics might be too high to be sufficiently protective. Insight in the actual
      internal exposure, the toxic agent, the appropriate dose metric, and whether an
      effect is related to internal concentration or dose is important. Without this,
      application of assessment factors on an external dose metric and the conversion
      to continuous exposure results in an uncertain human health risk assessment of
      inhalation exposures.

PMID- 29030270
TI  - Preliminary data on citrinin kinetics in humans and their use to estimate
      citrinin exposure based on biomarkers.
AB  - Citrinin (CIT), a fungal metabolite causing nephrotoxicity, has a tolerable daily
      intake (TDI) value of 0.2MUg/kg bw. Contamination of food with CIT is not
      sufficiently known to allow dietary exposure assessment. Urinary biomonitoring
      data are available from cohorts of several countries. However, kinetic
      information is lacking for CIT, hampering the use of urinary biomonitoring data
      to estimate the daily intake. We have investigated the kinetics of CIT after oral
      intake in two human volunteers on two occasions. Urinary excretion showed that
      ingested CIT undergoes conversion to dihydro-citrinone (DH-CIT) which is then
      excreted in the urine along with parent compound. The cumulative urinary
      excretion within 24h was between 32.9% and 70.8% (median 40.2%) of the sum of CIT
      and DH-CIT ('total CIT'). The median half-life in urine was 6.7h for CIT and 8.9h
      for DH-CIT. The median half-life in plasma accounted to 9.4h. The daily urinary
      excretion for 'total CIT' served to estimate a provisional daily CIT intake using
      published urine biomarker data in several cohorts. European cohorts had an
      exposure well below the TDI whereas in Bangladesh the exposure in one cohort
      exceeded the TDI.

PMID- 29030271
TI  - NOAEL-dose of a neonicotinoid pesticide, clothianidin, acutely induce anxiety
      related behavior with human-audible vocalizations in male mice in a novel
      environment.
AB  - Neonicotinoids are novel systemic pesticides acting as agonists on the nicotinic
      acetylcholine receptors (nAChRs) of insects. Experimental studies have revealed
      that neonicotinoids pose potential risks for the nervous systems of non-target
      species, but the brain regions responsible for their behavioral effects remain
      incompletely understood. This study aimed to assess the neurobehavioral effects
      of clothianidin (CTD), a later neonicotinoid developed in 2001 and widely used
      worldwide, and to explore the target regions of neonicotinoids in the mammalian
      brain. A single-administration of 5 or 50mg/kg CTD to male C57BL/6N mice at or
      below the no-observed-adverse-effect level (NOAEL) induced an acute increase in
      anxiety during the elevated plus-maze test. In addition, mice in the CTD
      administered group spontaneously emitted human-audible vocalizations (4-16kHz),
      which are behavioral signs of aversive emotions, and showed increased numbers of
      c-fos immunoreactive cells in the paraventricular thalamic nucleus and dentate
      gyrus of the hippocampus. In conclusion, mice exposed to NOAEL-dose CTD would be
      rendered vulnerable to a novel environment via the activation of thalamic and
      hippocampal regions related to stress responses. These findings should provide
      critical insight into the neurobehavioral effects of neonicotinoids on mammals.

PMID- 29030272
TI  - Impact of fasting followed by short-term exposure to interleukin-6 on cytochrome
      P450 mRNA in mice.
AB  - The gene expression of the cytochrome P450 (CYP) enzyme family is regulated by
      numerous factors. Fasting has been shown to induce increased hepatic CYP mRNA in
      both humans and animals. However, the coordinated regulation of CYP, CYP
      regulating transcription factors, and transcriptional co-factors in the liver
      linking energy metabolism to detoxification has never been investigated.
      Interleukin-6 (IL-6) has been suggested to be released during fasting and has
      been shown to regulate CYP expression. The present study investigated the hepatic
      mRNA content of selected CYP, AhR, CAR, PXR and PPARalpha in mice fasted for 18h
      and subsequently exposed to IL-6. Furthermore, the impact of fasting on PGC
      1alpha, HNF-4alpha, SIRT1 and SIRT3 mRNA was examined. Fasting induced a marked
      increase in Cyp2b10, Cyp2e1 and Cyp4a10 mRNA, while CYP1a1, Cyp1a2, Cyp2a4 and
      Cyp3a11 mRNA levels remained unchanged. In accordance, the mRNA levels of CAR and
      PPARalpha were also increased with fasting. The PGC-1alpha, SIRT1 and SIRT3 mRNA
      levels were also increased after fasting, while the HNF-4alpha mRNA levels
      remained unchanged. In mice subjected to IL-6 injection, the fasting-induced PXR,
      PPARalpha and PGC-1alpha mRNA responses were lower than after saline injection.
      In conclusion, fasting was demonstrated to be a strong inducer of hepatic CYP
      mRNA as well as selected transcription factors controlling the expression of the
      investigated CYP. Moreover, the mRNA levels of transcriptional co-factors acting
      as energy sensors and co-factors for CYP regulation was also increased in the
      liver, suggesting crosstalk at the molecular level between regulation of energy
      metabolism and detoxification.

PMID- 29030273
TI  - Heterologous production of myxobacterial alpha-pyrone antibiotics in Myxococcus
      xanthus.
AB  - Myxopyronins (MXN) and corallopyronins (COR) are structurally related alpha
      pyrone antibiotics from myxobacteria that represent a highly promising compound
      class for the development of broad-spectrum antibacterial therapeutic agents.
      Their ability to inhibit RNA polymerase through interaction with the "switch
      region", a novel target, distant from previously characterized RNA polymerase
      inhibitors (e.g. rifampicin), makes them particularly promising candidates for
      further research. To improve compound supply for further investigation of MXN,
      COR and novel derivatives of these antibacterial agents, establishment of an
      efficient and versatile microbial production platform for myxobacterial alpha
      pyrone antibiotics is highly desirable. Here we describe design, construction and
      expression of a heterologous production and engineering platforms for MXN and COR
      to facilitate rational structure design and yield improvement approaches in the
      myxobacterial host strain Myxococcus xanthus DK1622. Optimization of the
      cultivation medium yielded significantly higher production titers of MXN A at
      around 41-fold increase and COR A at around 25-fold increase, compared to the
      standard CTT medium.

PMID- 29030274
TI  - Predicting novel substrates for enzymes with minimal experimental effort with
      active learning.
AB  - Enzymatic substrate promiscuity is more ubiquitous than previously thought, with
      significant consequences for understanding metabolism and its application to
      biocatalysis. This realization has given rise to the need for efficient
      characterization of enzyme promiscuity. Enzyme promiscuity is currently
      characterized with a limited number of human-selected compounds that may not be
      representative of the enzyme's versatility. While testing large numbers of
      compounds may be impractical, computational approaches can exploit existing data
      to determine the most informative substrates to test next, thereby more
      thoroughly exploring an enzyme's versatility. To demonstrate this, we used
      existing studies and tested compounds for four different enzymes, developed
      support vector machine (SVM) models using these datasets, and selected additional
      compounds for experiments using an active learning approach. SVMs trained on a
      chemically diverse set of compounds were discovered to achieve maximum accuracies
      of ~80% using ~33% fewer compounds than datasets based on all compounds tested in
      existing studies. Active learning-selected compounds for testing resolved
      apparent conflicts in the existing training data, while adding diversity to the
      dataset. The application of these algorithms to wide arrays of metabolic enzymes
      would result in a library of SVMs that can predict high-probability promiscuous
      enzymatic reactions and could prove a valuable resource for the design of novel
      metabolic pathways.

PMID- 29030275
TI  - Metabolite damage and repair in metabolic engineering design.
AB  - The necessarily sharp focus of metabolic engineering and metabolic synthetic
      biology on pathways and their fluxes has tended to divert attention from the
      damaging enzymatic and chemical side-reactions that pathway metabolites can
      undergo. Although historically overlooked and underappreciated, such metabolite
      damage reactions are now known to occur throughout metabolism and to generate
      (formerly enigmatic) peaks detected in metabolomics datasets. It is also now
      known that metabolite damage is often countered by dedicated repair enzymes that
      undo or prevent it. Metabolite damage and repair are highly relevant to
      engineered pathway design: metabolite damage reactions can reduce flux rates and
      product yields, and repair enzymes can provide robust, host-independent
      solutions. Herein, after introducing the core principles of metabolite damage and
      repair, we use case histories to document how damage and repair processes affect
      efficient operation of engineered pathways - particularly those that are
      heterologous, non-natural, or cell-free. We then review how metabolite damage
      reactions can be predicted, how repair reactions can be prospected, and how
      metabolite damage and repair can be built into genome-scale metabolic models.
      Lastly, we propose a versatile 'plug and play' set of well-characterized
      metabolite repair enzymes to solve metabolite damage problems known or likely to
      occur in metabolic engineering and synthetic biology projects.

PMID- 29030276
TI  - Dental occlusal-surface-supported titanium guide to assist cutting and drilling
      in mandibular bilateral sagittal split osteotomy.
AB  - INTRODUCTION: Cutting and drilling guides manufactured using computer-aided
      design/computer-aided manufacturing (CAD/CAM) technologies have attracted
      increasing interest in orthognathic surgery, particularly in complex cases. The
      development of these guides requires virtual surgery planning and three
      dimensional modelling before they can be printed in titanium, polyamide or resin.
      We report the use of a personalized titanium device to assist bilateral sagittal
      split osteotomy (BSSO) with or without genioplasty combined with individual
      implants for repositioning and fixation. This one-piece guide for both sides of
      the BSSO allows the initiation of cutting and drilling with less invasive drill
      placement and greater accuracy. PROCEDURE: The titanium guide was manufactured
      using CAD/CAM technologies after conventional digital planning of BSSO.
      Intraoperatively, the guide was fitted on each side of the mandibular occlusal
      surface and screwed to predesigned drill holes. The guide facilitates the
      predrilling of screw holes and the initiation of cutting for buccal, lingual and
      external oblique ridge corticotomy using a piezosurgery device. CONCLUSION: Based
      on our experience, we think that this guide is a promising new tool to assist
      BSSO. It helped limit the extent of tissue detachment required and provided the
      strength necessary for accurate bone cutting and drilling. It also allowed the
      accurate fixation of preformed plates to obtain occlusion as per virtual
      planning.

PMID- 29030277
TI  - Isolated unilateral temporalis muscle hypertrophy: First case in an 8-year-old
      boy and review.
AB  - INTRODUCTION: Isolated unilateral temporalis muscle hypertrophy (IUTMH) was first
      described in 1990 and few cases have been published since then. This disease
      occurs mainly in adults. There is no clear etiology of IUTMH, but bruxism is one
      of the risk factors. Only two cases have been described before the age of 20
      years. To our knowledge, no cases have been described in persons younger than 15
      years old. We report the first case of IUTMH in an 8-year-old and review the
      literature. MATERIAL AND METHODS: This section is separated into 3 parts: (1)
      search for and description of clinical cases of IUTMH in our department; (2)
      literature search to find similar cases; (3) data analysis of all cases found.
      RESULTS: Ten patients, including our case, were found over a period of 23 years:
      five females and five males with a mean age of 32.8 years. One patient was 15
      years old. Time between onset and diagnosis was 16.7 months. Half of the patients
      reported pain and three had experienced bruxism. Most of the patients had non
      surgical treatment. One patient evolved favorably with no treatment. One
      recurrence occurred 10 years later. DISCUSSION: IUTMH can occur in childhood in a
      high-stress environment. Diagnosis is based on the history and clinical and
      imaging findings. Biopsy helps to confirm the diagnosis, but electromyograms and
      neurological tests contribute little. Bruxism should be taken into account. The
      treatment with the least inconvenience must be given.

PMID- 29030278
TI  - Maxillofacial Mazabraud's syndrome: A case report & review.
AB  - Mazabraud's syndrome is characterized by myxomas of intramuscular type present in
      association with fibrous dysplasia. Up to this day, approximately 80 cases of
      Mazabraud's syndrome have been reported, although in the head and neck territory
      intramuscular myxoma reports in association with fibrous dysplasia of the bone
      are very scarce. An unusual case of Mazabraud's syndrome in a 63 years old female
      displaying fibrous dysplasia of the mandible and soft tissue myxoma in the
      edentulous alveolar ridge in the molar area is reported. After four years of
      follow-up, the clinical, imagenological and microscopical findings that led to
      the diagnosis and treatment are discussed. This report exemplifies the diagnostic
      and treatment challenge of this rare disease and enhances our clinical knowledge
      due to its long follow-up, highlighting the need of understanding better its
      behavior in order to establish proper guidelines for its treatment.

PMID- 29030279
TI  - Posterior cranial vault distraction osteogenesis in craniofacial surgery:
      Technical note.
AB  - INTRODUCTION: Posterior cranial vault distraction is a treatment for intracranial
      hypertension in certain cases of craniosynostosis and faciocraniosynostosis. It
      allows the harmonization of the skull back and prevents turricephaly. This study
      presents the surgical technique. TECHNICAL NOTE: Posterior cranial vault
      distraction osteogenesis consists of a circular osteotomy of the skull back. Four
      distractors are placed on the cranial flap without detachment of the dura mater.
      The distraction is carried out over nearly 1 month with an objective of 20mm. The
      technique's effectiveness is judged on the correction of the skull back shape and
      the disappearance of clinical and radiological signs of intracranial
      hypertension. DISCUSSION: Posterior cranial vault distraction osteogenesis
      enables a large increase in cranial volume and a correction of the dysmorphic
      skull back. This easy surgery and the low rate of complications make this
      technique a main surgical approach in the management of faciocraniosynostosis.

PMID- 29030281
TI  - Disc repositioning plus temporal eminectomy for temporomandibular joint internal
      derangement: A pilot study.
AB  - INTRODUCTION: Temporomandibular joint internal derangement is a common disorder,
      which usually resolves with conservative management. However, 5% of patients
      require surgery and although many techniques have been described, a gold standard
      surgical procedure has not yet been established. OBJECTIVES: The aim of this
      study was to compare the clinical outcome of disc repositioning plus temporal
      eminectomy versus disc repositioning alone, for the treatment of
      temporomandibular joint internal derangement. METHODOLOGY: Matched case-control
      retrospective pilot study. Records of patients diagnosed with temporomandibular
      joint internal derangement from January 2010 to December 2015 were studied.
      Eleven patients treated with disc repositioning plus temporal eminectomy for the
      case group and 11 patients treated with disc repositioning alone for the age- and
      gender-matched control group. RESULTS: No difference was found in terms of pain,
      noise or blockage with the maximum oral opening between the groups at the first
      or sixth month after surgery. However, there were differences in movement
      restriction at the first and sixth month after surgery, in favor of the temporal
      eminectomy group. These differences were statistically significant only at the
      sixth month after surgery (P: 0.03). CONCLUSIONS: Our results suggest that disc
      repositioning plus temporal eminectomy could be a short-term benefit in terms of
      mobility and oral opening. However, larger samples and prospective trials will be
      necessary to corroborate the current findings.

PMID- 29030280
TI  - Mobilization of malpositioned dental implant using segmental osteotomy: A case
      report.
AB  - By increasing the number of replaced tooth with dental implants, the number of
      poorly positioned implants is also increased. In this article, we present our
      experience about a 48-year-old female who was referred to our department for
      resolving prosthetic problem regarding two malpositioned implants inserted in the
      upper jaw. The interocclusal space was insufficient and the two adjacent implants
      had excessive buccal angulation. To overcome these problems, segmental osteotomy
      of the alveolar bone containing two implants has been done. After palatal and
      apical repositioning of the bone block, rigid fixation was performed using a 4
      hole miniplate and four 5mm monocortical screws. Two weeks after the procedure, a
      conventional fixed prosthesis was constructed with regard to the esthetic and
      functional aspects. During the two-year follow-up, the patient was satisfied with
      the result and there were no complications, such as alveolar bone necrosis,
      marginal bone loss, implant failure or infection.

PMID- 29030282
TI  - Epithelioid hemangioendothelioma, an uncommon tumor of the eyelid: A case report.
AB  - Epithelioid hemangioendothelioma (EHE) is an infrequent vascular tumor that has
      an intermediate prognosis between the prognosis of the angioma and that of the
      angiosarcoma. Its evolution is characterized by a tendency to recurrence and
      metastases. EHE has been reported in locations such as: lungs, liver, bone and
      soft tissues. There are very few reports of cases involving the head and neck
      region. The occurrence of EHE in the orbital region and/or the eyelid is
      extremely rare. The authors report a case of EHE in the right upper eyelid.
      Surgical excision has been performed resulting in a good local control of the
      disease after a 5-year follow up.

PMID- 29030283
TI  - Logistics of Three-dimensional Printing: Primer for Radiologists.
AB  - The Association of University Radiologists Radiology Research Alliance Task Force
      on three-dimensional (3D) printing presents a review of the logistic
      considerations for establishing a clinical service using this new technology,
      specifically focused on implications for radiology. Specific topics include
      printer selection for 3D printing, software selection, creating a 3D model for
      printing, providing a 3D printing service, research directions, and opportunities
      for radiologists to be involved in 3D printing. A thorough understanding of the
      technology and its capabilities is necessary as the field of 3D printing
      continues to grow. Radiologists are in the unique position to guide this emerging
      technology and its use in the clinical arena.

PMID- 29030284
TI  - Structured Reporting in Radiology.
AB  - Radiology reports are vital for patient care as referring physicians depend upon
      them for deciding appropriate patient management. Traditional narrative reports
      are associated with excessive variability in the language, length, and style,
      which can minimize report clarity and make it difficult for referring clinicians
      to identify key information needed for patient care. Structured reporting has
      been advocated as a potential solution for improving the quality of radiology
      reports. The Association of University Radiologists-Radiology Research Alliance
      Structured Reporting Task Force convened to explore the current and future role
      of structured reporting in radiology and summarized its finding in this article.
      We review the advantages and disadvantages of structured radiology reports and
      discuss the current prevailing sentiments among radiologists regarding structured
      reports. We also discuss the obstacles to the use of structured reports and
      highlight ways to overcome some of those challenges. We also discuss the future
      directions in radiology reporting in the era of personalized medicine.

PMID- 29030285
TI  - Clinical Applications of 3D Printing: Primer for Radiologists.
AB  - Three-dimensional (3D) printing refers to a number of manufacturing technologies
      that create physical models from digital information. Radiology is poised to
      advance the application of 3D printing in health care because our specialty has
      an established history of acquiring and managing the digital information needed
      to create such models. The 3D Printing Task Force of the Radiology Research
      Alliance presents a review of the clinical applications of this burgeoning
      technology, with a focus on the opportunities for radiology. Topics include uses
      for treatment planning, medical education, and procedural simulation, as well as
      patient education. Challenges for creating custom implantable devices including
      financial and regulatory processes for clinical application are reviewed.
      Precedent procedures that may translate to this new technology are discussed. The
      task force identifies research opportunities needed to document the value of 3D
      printing as it relates to patient care.

PMID- 29030286
TI  - Peptides Acting as Cognitive Enhancers.
AB  - The aim of this paper is to present an overview of three peptides that, by
      improving synaptic function, enhance learning and memory in laboratory rodents.
      We summarize their structure, their mechanisms of action, and their effects on
      synaptic and cognitive function. First we describe FGL, a peptide derived from
      the neural cell adhesion molecule which improves cognition by the activation of
      the PKC pathway that triggers an activity-dependent delivery of AMPA receptors to
      the synapses. Then we describe PTD4-PI3KAc peptide that by activating PI3K
      signaling pathway it promotes synapse and spine formation and enhances
      hippocampal dependent memory. Lastly, we describe a new peptide derived from the
      well-known tumor suppressor PTEN that prevents pathological interactions between
      PTEN and PDZ proteins at synapses during exposure to Amyloid beta. This action
      prevents memory deterioration in mouse model of Alzheimer's disease. Together,
      this review indicates how learning and memory can be improved by manipulating
      synaptic function and number through pharmacological treatment with peptides, and
      it establishes synaptic function as a valid target for cognitive enhancement.

PMID- 29030287
TI  - Inhibition of Pain and Pain-Related Brain Activity by Heterotopic Noxious Counter
      Stimulation and Selective Attention in Chronic Non-Specific Low Back Pain.
AB  - The aim of the present study was to assess inhibition of pain and somatosensory
      evoked potentials (SEPs) by heterotopic noxious counter-stimulation (HNCS) and by
      selective attention in patients with chronic non-specific LBP. Seventeen patients
      and age/sex-matched controls were recruited (10 men, 7 women; mean age +/- SD:
      43.3 +/- 10.4 and 42.7 +/- 11.1, respectively). On average, patients with LBP
      reported pain duration of 7.6 +/- 6.5 years, light to moderate disability (19.3
      +/- 5.7/100) and low clinical pain intensity (21.8 +/- 1.5/100), while pain
      catastrophizing, state and trait anxiety and depressive symptoms were not
      significantly different between groups (all p's >0.05). HNCS and selective
      attention had differential inhibitory effects on pain and SEP, but no difference
      was observed between groups. Across both groups, HNCS decreased pain (p = 0.06)
      as well as the N100 and the N150 components of SEP (p's <0.001), while selective
      attention only decreased pain (p < 0.01) and the N100 (p<0.001). In contrast, the
      P260 was decreased by HNCS only when attention was directed toward the HNCS
      stimulus (p<0.01). This indicates that patients with the characteristics
      described above do not show altered pain inhibitory mechanisms involved in HNCS
      and selective attention. Importantly, this experiment was carefully designed to
      control for non-specific effects associated with the repetition of the test
      stimulus and the effect of an innocuous counter-stimulation. It remains to be
      determined if these results hold for patients with severe LBP and psychological
      symptoms or whether symptom severity may be associated with pain inhibition
      deficits.

PMID- 29030288
TI  - In vitro characterization of zebrafish (Danio rerio) organic anion transporters
      Oat2a-e.
AB  - OATS/Oats are transmembrane proteins that transport a variety of drugs,
      environmental toxins and endogenous metabolites into the cell. Zebrafish (Danio
      rerio) has seven OAT orthologs: Oat1, Oat2a-e and Oat3. In this study we
      specifically address Oat2 (Slc22a7) family. Conserved synteny analysis showed
      localization of zebrafish oat2 genes on two chromosomes, 11 and 17. All five
      zebrafish Oats were localized by live cell imaging in membranes of transiently
      transfected HEK293-T cells, and Oat2a, b, d, and e were confirmed using western
      blot analysis. Functional studies using the HEK293T cells overexpressing
      zebrafish Oats revealed two model fluorescent substrates of three Oats: Lucifer
      yellow for Oat2a and Oat2d (Km 122, and 49.7MUM), and 6-carboxyfluorescein for
      Oat2b and Oat2d (Km 199.7, and 266.9MUM). The initial screening of a series of
      diverse endo- and xenobiotics showed interaction with a number of compounds,
      including cGMP and diclofenac (IC50 27.74, and 19.14MUM) with Oat2a; estrone-3
      sulfate and diclofenac (IC50 30.96, and 12.6MUM) with Oat2b; and fumarate and
      indomethacin (IC50 68.24, and 20.41MUM) with Oat2d. This study provides the first
      comprehensive data set on Oat2 in zebrafish and offers an important basis for
      more detailed molecular and (eco)toxicological characterizations of these
      transporters.

PMID- 29030289
TI  - Thermal properties of compacted pharmaceutical excipients.
AB  - Thermal properties of powders are critical material attributes that control
      temperature rise during tableting and roll compaction. In this study, various
      analytical methods were used to measure the thermal properties of widely used
      pharmaceutical excipients including microcrystalline cellulose (MCC) of three
      different grades (Avicel PH 101; Avicel PH 102 and Avicel DG), lactose and
      mannitol. The effect of relative density on the measured thermal properties was
      investigated by compressing the powders into specimen of different relative
      densities. Differential thermal analysis (DTA) was employed to explore
      endothermic or exothermic events in the temperature range endured during typical
      pharmaceutical manufacturing processes, such as tabletting and roll compaction.
      Thermogravimetric analysis (TGA) was performed to analyse the water/solvent
      content, either in the form as solvates or as loosely bound molecules on the
      particle surface. Thermal conductivity analysis (TCA) was conducted to measure
      thermal conductivity and volumetric heat capacity. It is shown that, for the MCC
      powders, almost no changes in morphology or structural changes were observed
      during heating to temperatures up to 200 degrees C. An increase in relative
      density or temperature leads to a high thermal conductivity and the volumetric
      heat capacity. Among all MCC powders considered, Avicel DG showed the highest
      increase in thermal conductivity and the volumetric heat capacity, but this heat
      capacity was not sensitive to the measurement temperature. For lactose and
      mannitol, some endothermic events occurred during heating. The thermal
      conductivity increased with the increase in temperature and relative density. A
      model was also developed to describe the variation of the thermal conductivity
      and the volumetric heat capacity with the relative density and the temperature.
      It was shown that the empirical model can well predict the dependency of the
      thermal conductivity and the volumetric heat capacity on the relative density and
      the temperature.

PMID- 29030290
TI  - Ex vivo evaluation of degradation rates of metronidazole and olsalazine in distal
      ileum and in cecum: The impact of prandial state.
AB  - PURPOSE: Evaluate ex vivo the bacterial metabolism induced degradation rates of
      mesalamine (negative control), metronidazole and olsalazine in distal ileum and
      in cecum. METHODS: The contents of distal ileum and cecum were collected during
      colonoscopy under anaerobic conditions from twelve healthy adults in the fasted
      and in the fed state. To eliminate potential effects of enzymes that may exist in
      the fluid of lower intestine, each sample was ultracentrifuged and the
      precipitate was diluted with a volume of normal saline equivalent to that of the
      supernatant, after ultracentrifugation of intestinal contents from which the
      specific precipitate had been obtained. Degradation of the three model drugs in
      individual materials was evaluated anaerobically. RESULTS: Mesalamine was stable
      in all cases. Degradation rates of metronidazole and olsalazine were higher in
      cecum than in distal ileum, only in the fasted state; no trend could be observed
      in the fed state. Degradation rates of metronidazole and olsalazine were
      decreased in the fed state in the cecum; no trend could be observed in distal
      ileum. CONCLUSIONS: In the fasted state, bacterial activity is higher in cecum
      than in distal ileum. Food residues decrease bacterial metabolism degradation
      rates of drugs in cecum.

PMID- 29030291
TI  - Evaluation of a Spray-type, Novel Dextrin Hydrogel Adhesion Barrier Under
      Laparoscopic Conditions in a Porcine Uterine Horn Adhesion Model.
AB  - STUDY OBJECTIVE: To establish a porcine uterine horn adhesion model that mimicked
      laparoscopic procedures and use it to investigate the effect of a spray-type,
      novel dextrin hydrogel adhesion barrier (AdSpray; Terumo Corporation, Tokyo,
      Japan) on postsurgical adhesions. DESIGN: A single-blind randomized controlled
      trial (Canadian Task Force Classification I). SETTING: A Certified animal
      research facility. SUBJECTS: Sixteen female pigs. INTERVENTIONS: All animals
      underwent laparoscopically assisted adhesion-inducing surgery. The uterine horns
      and the peritoneum of the pelvic sidewall were injured. In the experimental
      group, AdSpray was applied to the injured site, and the handling of the sprayer
      was assessed. At 28 +/- 1 days after surgery, animals were sacrificed, and
      adhesions at the injured site were evaluated. Uterine horn suture sites were
      examined under a light microscope to assess healing of the incised wound, the
      inflammatory reaction, abscess, and the foreign body reaction to the surgical
      suture. MEASUREMENTS AND MAIN RESULTS: The control group showed severe adhesions
      over the entire surface interface at the uterine horn suture sites and peritoneal
      resection site. Compared with the control treatment, AdSpray exhibited a higher
      percentage of adhesion-free sites (p < .001) and reduced the total adhesion score
      (p < .001). In the AdSpray group, no inflammation or abscess formation was
      observed on histopathological examination, and ideal healing of the suture sites
      was confirmed in all cases. CONCLUSION: Based on the results of the present
      study, the novel dextrin hydrogel shows excellent adhesion prevention and can be
      easily applied during laparoscopy using a dedicated sprayer.

PMID- 29030292
TI  - Multidisciplinary Resection of Deeply Infiltrative Endometriosis.
AB  - STUDY OBJECTIVE: To describe a multidisciplinary approach for the resection of
      deeply infiltrative endometriosis using the robotic platform. DESIGN: A technical
      video showing a step-by-step approach for the resection of deeply infiltrative
      endometriosis (Canadian Task Force classification level III). Institutional
      review board approval was not required for this study. SETTING: There is
      considerable involvement of the bowel and bladder with deeply infiltrative
      endometriosis [1-3]. The need for operative procedures involving multiple organs
      while performing a complete resection is common. The benefits of minimally
      invasive surgery for a gynecologic pathology have been documented in numerous
      studies. Patients had fewer medical and surgical complications postoperatively,
      better cosmesis, and better quality of life [4-6]. We believe that deeply
      infiltrative endometriosis does not preclude patients from having a minimally
      invasive resection procedure. In this video, we describe how the robotic platform
      was used for a seamless transition between surgical specialties including
      gynecology, colorectal, and urology to ensure complete resection of endometriosis
      lesions involving multiple organs. PATIENT: A 47-year-old woman with a 4-year
      history of severe pelvic pain, dysuria, dyspareunia, dyschezia, and dysmenorrhea
      failing multiple medical therapies presented to our clinic to discuss surgical
      options. After thorough counseling, the decision was made to proceed with
      definitive surgical management. Postoperatively, the patient was admitted for 2
      days of postoperative inpatient care. After meeting all immediate postoperative
      milestones, she was discharged with an indwelling Foley catheter and instructed
      to follow up in the clinic with all 3 surgical specialties. At the 1-week
      interval, she was seen by the urology team; her indwelling catheter was removed
      after a cystoscopy was performed documenting adequate healing. Two weeks
      postoperatively, the patient was seen by the gynecology and colorectal teams and
      was noted to be healing adequately from the procedure. Her six-week visit was
      also unremarkable. She continued to follow up with the gynecology team for her
      yearly well-woman examinations and has been symptom free for 2 years after the
      surgery. She takes norethindrone daily to minimize recurrence. INTERVENTIONS:
      Preoperative pelvic magnetic resonance imaging (MRI) showed bladder endometriosis
      and extensive rectovaginal endometriosis. We describe the multidisciplinary
      approach used for surgery and the procedures performed by each specialty. The
      urology team performed a cystoscopy preoperatively to assess for full-thickness
      erosions and the location of those lesions in that event. The urology team also
      reviewed the magnetic resonance images with the radiology team, and the
      endometriosis lesions were suspected to be close to the bladder trigone, keeping
      in mind that this finding could be overestimated given that the bladder was
      deflated at the time the imaging was obtained. Accordingly, at the time of
      surgery, the decision was made to proceed with cystoscopy and the placement of
      ureteral stents as a prophylactic measure. An intentional cystotomy and resection
      of the bladder section involved with endometriosis were performed followed by
      watertight closure. The trigone area of the bladder was not involved, and
      ureteral reimplantation was not needed in this case. The gynecology team operated
      second and performed an extensive dissection of the retroperitoneal space with
      the development of the pararectal and paravesical spaces. They also ligated the
      uterine artery at its origin followed by dissection of the uterovesical space,
      effectively reflecting the bladder off of the lower uterine segment. At this
      point, they proceeded with a total hysterectomy, and the specimen was removed
      from the pelvis through the vaginal cuff. Preoperatively, the colorectal surgeon
      ordered a colonoscopy to determine if full-thickness erosions were present and
      reviewed the magnetic resonance images with the radiology team. Based on the MRI
      and colonoscopy, all patients are counseled and consented for the possibility of
      a low anterior resection and loop ileostomy to protect the anastomosis. Based on
      the understanding that colorectal and gynecologic surgeries have a different
      approach when dissecting the pararectal space at our institution, a discussion
      between the 2 teams is initiated at the multidisciplinary session for surgery
      planning. In the case we present, the colorectal surgeon opted for the removal of
      the uterus before his dissection was initiated given that he dissects this space
      presacrally and not retroperitoneally like the gynecology counterpart. He would
      also benefit from the extra space for dissection with the uterus out of the
      pelvis. The colorectal part of the case was initiated by mobilization of the
      rectum and dissecting the obliterated rectovaginal space. The presacral space was
      then opened followed by mobilization of the rectosigmoid from its attachment. The
      case was concluded with full transection and reanastomosis of the rectum section
      involved with endometriosis. The specimen was also removed from the pelvis
      through the vaginal cuff. MEASUREMENTS AND MAIN RESULTS: Complete resection of
      deeply infiltrative endometriosis spanning beyond the scope of 1 surgical
      specialty. No immediate intraoperative, perioperative, or long-term complications
      from surgery. Complete resolution of endometriosis symptoms. CONCLUSION: We
      encourage collaborative care for planning and performing comprehensive and safe
      resection of deeply infiltrative endometriosis.

PMID- 29030293
TI  - Solving probability reasoning based on DNA strand displacement and probability
      modules.
AB  - In computation biology, DNA strand displacement technology is used to simulate
      the computation process and has shown strong computing ability. Most researchers
      use it to solve logic problems, but it is only rarely used in probabilistic
      reasoning. To process probabilistic reasoning, a conditional probability
      derivation model and total probability model based on DNA strand displacement
      were established in this paper. The models were assessed through the game "read
      your mind." It has been shown to enable the application of probabilistic
      reasoning in genetic diagnosis.

PMID- 29030294
TI  - Type I interferon pathway activation in COPA syndrome.
AB  - Mutations of the COPA gene cause an immune dysregulatory disease characterised by
      polyarticular arthritis and progressive interstitial lung disease with pulmonary
      haemorrhages. We report the case of a young girl that presented at age 3 with
      polyarticular arthritis, chronic cough and high titer rheumatoid factor.
      Radiologic imaging showed interstitial lung disease with tree-in-a-bud nodules
      and air-filled cysts. Targeted genetic analysis of COPA gene showed the reported
      c.698G>A mutation. The patient was lost to follow up for 3years during which
      therapy was discontinued with the development of joint damage and deformities.
      Analysis of peripheral blood showed activation of type 1 interferon pathway,
      which was also confirmed in 4 previously reported COPA patients. Our observations
      underline the importance of early treatment in COPA disease to avoid loss of
      joint function. Furthermore, our results suggest a role for type 1 interferon in
      disease pathogenesis opening the possibility for targeted therapeutic approaches.

PMID- 29030295
TI  - The new phylogeny of the genus Mycobacterium: The old and the news.
AB  - BACKGROUND: Phylogenetic studies of bacteria have been based so far either on a
      single gene (usually the 16S rRNA) or on concatenated housekeeping genes. For
      what concerns the genus Mycobacterium these approaches support the separation of
      rapidly and slowly growing species and the clustering of most species in well
      defined phylogenetic groups. The advent of high-throughput shotgun sequencing
      leads us to revise conventional taxonomy of mycobacteria on the light of genomic
      data. For this purpose we investigated 88 newly sequenced species in addition to
      60 retrieved from GenBank and used the Average Nucleotide Identity pairwise
      scores to reconstruct phylogenetic relationships within this genus. RESULTS: Our
      analysis confirmed the separation of slow and rapid growers and the intermediate
      position occupied by the M. terrae complex. Among the rapid growers, the species
      of the M. chelonae-abscessus complex belonged to the most ancestral cluster.
      Other major clades of rapid growers included the species related to M. fortuitum
      and M. smegmatis and a large grouping containing mostly environmental species
      rarely isolated from humans. The members of the M. terrae complex appeared as the
      most ancestral slow growers. Among slow growers two deep branches led to the
      clusters of species related to M. celatum and M. xenopi and to a large group
      harboring most of the species more frequently responsible of disease in humans,
      including the major pathogenic mycobacteria (M. tuberculosis, M. leprae, M.
      ulcerans). The species previously grouped in the M. simiae complex were allocated
      in a number of sub-clades; of them, only the one including the species M. simiae
      identified the real members of this complex. The other clades included also
      species previously not considered related to M. simiae. The ANI analysis, in most
      cases supported by Genome to Genome Distance and by Genomic Signature-Delta
      Difference, showed that a number of species with standing in literature were
      indeed synonymous. CONCLUSIONS: Genomic data revealed to be much more informative
      in comparison with phenotype. We believe that the genomic revolution enabled by
      high-throughput shotgun sequencing should now be considered in order to revise
      the conservative approaches still informing taxonomic sciences.

PMID- 29030296
TI  - Modulating influences of memory strength and sensitivity of the retrieval test on
      the detectability of the sleep consolidation effect.
AB  - Emotionality can increase recall probability of memories as emotional information
      is highly relevant for future adaptive behavior. It has been proposed that memory
      processes acting during sleep selectively promote the consolidation of emotional
      memories, so that neutral memories no longer profit from sleep consolidation
      after learning. This appears as a selective effect of sleep for emotional
      memories. However, other factors contribute to the appearance of a consolidation
      benefit and influence this interpretation. Here we show that the strength of the
      memory trace before sleep and the sensitivity of the retrieval test after sleep
      are critical factors contributing to the detection of the benefit of sleep on
      memory for emotional and neutral stimuli. 228 subjects learned emotional and
      neutral pictures and completed a free recall after a 12-h retention interval of
      either sleep or wakefulness. We manipulated memory strength by including an
      immediate retrieval test before the retention interval in half of the
      participants. In addition, we varied the sensitivity of the retrieval test by
      including an interference learning task before retrieval testing in half of the
      participants. We show that a "selective" benefit of sleep for emotional memories
      only occurs in the condition with high memory strength. Furthermore, this
      "selective" benefit disappeared when we controlled for the memory strength before
      the retention interval and used a highly sensitive retrieval test. Our results
      indicate that although sleep benefits are more robust for emotional memories,
      neutral memories similarly profit from sleep after learning when more sensitive
      indicators are used. We conclude that whether sleep benefits on memory appear
      depends on several factors, including emotion, memory strength and sensitivity of
      the retrieval test.

PMID- 29030299
TI  - Enhancing early consolidation of human episodic memory by theta EEG
      neurofeedback.
AB  - Consolidation of newly formed memories is readily disrupted, but can it be
      enhanced? Given the prominent role of hippocampal theta oscillations in memory
      formation and retrieval, we hypothesized that upregulating theta power during
      early stages of consolidation might benefit memory stability and persistence. We
      used EEG neurofeedback to enable participants to selectively increase theta power
      in their EEG spectra following episodic memory encoding, while other participants
      engaged in low beta-focused neurofeedback or passively viewed a neutral nature
      movie. Free recall assessments immediately following the interventions, 24h later
      and 7d later all indicated benefit to memory of theta neurofeedback, relative to
      low beta neurofeedback or passive movie-viewing control conditions. The degree of
      benefit to memory was correlated with the extent of theta power modulation, but
      not with other spectral changes. Theta enhancement may provide optimal conditions
      for stabilization of new hippocampus-dependent memories.

PMID- 29030298
TI  - Linking muscarinic receptor activation to UPS-mediated object memory
      destabilization: Implications for long-term memory modification and storage.
AB  - Consolidated memories can become destabilized during reactivation, resulting in a
      transient state of instability, a process that has been hypothesized to underlie
      long-term memory updating. Consistent with this notion, relatively remote
      memories, which are resistant to standard destabilization procedures, are
      reliably destabilized when novel information (i.e., the opportunity for memory
      updating) is present during reactivation. We have also shown that cholinergic
      muscarinic receptor (mAChR) activation can similarly destabilize consolidated
      object memories. Synaptic protein degradation via the ubiquitin proteasome system
      (UPS) has previously been linked to destabilization of fear and object-location
      memories. Given the role of calcium in regulating proteasome activity, we
      hypothesized that activation of cholinergic receptors, specifically M1 mAChRs,
      stimulates the UPS via inositol triphosphate receptor (IP3R)-mediated release of
      intracellular calcium stores to facilitate object memory destabilization. We
      present converging evidence for this hypothesis, which we tested using a modified
      spontaneous object recognition task for rats and microinfusions into perirhinal
      cortex (PRh), a brain region strongly implicated in object memory. We extend our
      previous findings by demonstrating that M1 mAChRs are necessary for novelty
      induced object memory destabilization. We also show that proteasome inhibition or
      IP3R antagonism in PRh prevents object memory destabilization induced by novelty
      or M1 mAChR stimulation. These results establish an intracellular pathway linking
      M1 receptors, IP3Rs, and UPS activity to object memory destabilization and
      suggest a previously unacknowledged role for cholinergic signaling in long-term
      memory modification and storage.

PMID- 29030297
TI  - Impaired extinction of cued fear memory and abnormal dendritic morphology in the
      prelimbic and infralimbic cortices in VPAC2 receptor (VIPR2)-deficient mice.
AB  - The structurally related neuropeptides vasoactive intestinal peptide (VIP) and
      pituitary adenylate cyclase-activating polypeptide (PACAP) have been implicated
      in stress regulation and learning and memory. Several bodies of research have
      shown the impact of the PACAP specific receptor PAC1 on fear memory, but the
      roles of other PACAP receptors in regulating fear stress responses remain to be
      elucidated. Here we aimed to investigate the effects of genetic deletion of VIPR2
      encoding the VPAC2 receptor, which binds both VIP and PACAP, on fear-related
      memory and on dendritic morphology in the brain regions of the fear circuitry.
      Male VPAC2 receptor knockout (VPAC2-KO) and littermate wild-type control mice
      were subjected to Pavlovian fear conditioning paradigm. VPAC2-KO mice displayed
      normal acquisition of fear conditioning, contextual and cued fear memory, but
      impaired extinction of cued fear memory. Morphological analyses revealed
      reductions in cell body size and total branch number and length of apical and
      basal dendrites of prelimbic cortex neurons in VPAC2-KO mice. In addition, Sholl
      analysis indicated that the amount of dendritic material distal to the soma was
      decreased, while proximal dendritic material was increased. In the infralimbic
      cortex, the amount of apical dendritic material proximal to the soma was
      increased in VPAC2-KO mice, while other indices of morphology did not differ.
      Finally, there were no differences in dendritic morphology in basolateral
      amygdala neurons between genotypes. These findings suggest that the VPAC2
      receptor plays an important role in the fear extinction processes and the
      regulation of the dendritic morphology in the prelimbic and infralimbic cortices.

PMID- 29030300
TI  - Gold nanocage decorated pH-sensitive micelle for highly effective photothermo
      chemotherapy and photoacoustic imaging.
AB  - : A pH-sensitive copolymer PAsp(DIP)-b-PAsp(MEA) (PDPM) was synthesized and self
      assembled to micelle loading chemotherapeutic drug doxorubicin (DOX) and
      introducing a gold nanocage structure for photothermo-chemotherapy and
      photoacoustic imaging. After further surface modification with polyethylene
      glycol (PEG), the DOX-loaded pH-sensitive gold nanocage (D-PGNC) around 100 nm
      possessed a uniform spherical structure with a pH-sensitive core of PAsp(DIP)
      incorporating DOX, an interlayer crosslinked via disulfide bonds and decorated
      with discontinuous gold shell, and a PEG corona. The release of DOX from D-PGNC
      was turned off in bloodstream due to the cross-linking and gold decoration of
      interlayer but turned on inside tumor tissue by multiple stimulations including
      the low pH value of tumor tissue (~6.8), the low lysosomal pH value of cancer
      cells (~5.0) and near-infrared (NIR) irradiation. The gold nanocage receiving NIR
      irradiation could generate hyperthermia to ablate tumor cells. Moreover, the
      photoacoustic (PA) imaging and analysis of DOX fluorescence inside tumor tissue
      demonstrated that photothermal therapy based on the gold nanocage effectively
      drove DOX penetration inside tumor. Owing to the rapid intratumor release and
      deep tissue penetration of drug favorable for killing cancer cells survived the
      photothermal therapy, the combined therapy based on D-PGNC via NIR irradiation
      exhibited a synergistic treatment effect superior to either chemotherapy or NIR
      induced photothermal therapy alone. STATEMENT OF SIGNIFICANCE: The novelty of the
      manuscript is its multifunctional system which incorporates anticancer drug DOX
      in its pH-sensitive core and acts as a template to introduce a gold nanocage.
      This nanomedicine presents potentials of sequestrating drug molecules in blood
      circulation but releasing them inside tumor upon responding to the acidic
      microenvironment therein. Exposure to NIR laser further expedited the pH
      sensitive DOX release and promoted DOX penetration into cancer tissues far away
      from the vasculature. Consequently, the combined photothermo-chemotherapy showed
      synergistic effects to inhibit tumor growth and prolong animal survival in nude
      mice bearing human SKOV-3 ovarian tumor. Moreover, owing to the decoration with
      gold nanocage, the tumor accumulation and intratumor diffusion of the micelles
      were easily trackable using photoacoustic imaging.

PMID- 29030302
TI  - Mesenchymal stem cell therapy for retro-corneal membrane - A clinical challenge
      in full-thickness transplantation of biosynthetic corneal equivalents.
AB  - : Artificial corneas (keratoprostheses) and biosynthetic collagen-based corneal
      equivalents are surgical implants designed to ease the global burden of corneal
      blindness. However, keratoprostheses in many cases fail due to development of
      fibrous retro-corneal membranes (RCM). Fibrous membranes which develop in the
      anterior chamber after prosthesis implantation do so on a matrix of fibrin. This
      study investigated fibrin deposition and RCM formation after full-thickness
      collagen-based hydrogel implants and compared them with syngeneic and allogeneic
      corneal grafts in mice. Fibrin cleared from the anterior chamber within 14 days
      in both allo- and syn-grafts but, persisted in hydrogel implants and developed
      into dense retro-corneal membrane (RCM) which were heavily infiltrated by
      activated myofibroblasts. In contrast, the number of CD11b+ macrophages
      infiltrating the initial deposition of fibrin in the anterior chamber (AC) after
      hydrogel implantation was markedly reduced compared to syn- and allo-grafts.
      Inoculation of mesenchymal stem cells prior to collagen gel implant promoted
      clearance of gel-associated fibrin from the anterior chamber. We propose that a
      failure of macrophage-mediated clearance of fibrin may be the cause of RCM
      formation after collagen-based hydrogel implants and that mesenchymal stem cell
      therapy promotes clearance of fibrin and prevents RCM formation. STATEMENT OF
      SIGNIFICANCE: The manuscript addresses the potential value of bone marrow-derived
      mesenchymal stem cell therapy for retro-corneal membrane (RCM) formation in full
      thickness transplantation of biosynthetic corneal equivalents. This work reports
      the pathophysiological changes in the anterior chamber of the mouse eye following
      full-thickness recombinant human cross-linked collagen-based hydrogel implants in
      which persistent fibrin promotes the development of dense RCM. Furthermore, pre
      treatment with mesenchymal stem cells reduces RCM formation and enhances corneal
      transparency.

PMID- 29030301
TI  - Biodegradable zwitterionic sulfobetaine polymer and its conjugate with paclitaxel
      for sustained drug delivery.
AB  - : A fully biodegradable zwitterionic polymer and the corresponding conjugate with
      paclitaxel (PTX) were synthesized as promising biomaterials. Allyl-functionalized
      polylactide (PLA) was employed as the precursor of polymer backbones. UV-induced
      thiol-ene reaction was conducted to conjugate thiol-functionalized sulfobetaine
      (SB) with the PLA-based backbone. The resulting zwitterionic polymer did not
      exhibit considerable cytotoxicity. A polymer-drug conjugate was also obtained by
      thiol-ene reaction of both thiol-functionalized SB and PTX with allyl
      functionalized PLA. The conjugate could readily form narrowly-dispersed
      nanoparticles in aqueous solutions with a volume-average hydrodynamic diameter
      (Dh,V) of 19.3 +/- 0.2 nm. Such a polymer-drug conjugate-based drug delivery
      system showed full degradability, well-suppressed non-specific interaction with
      biomolecules, and sustained drug release. In vitro assessments also confirmed the
      significant anti-cancer efficacy of the conjugate. After 72 h incubation with PLA
      SB/PTX containing 10 ug/mL of PTX, the cell viabilities of A549, MCF7, and PaCa-2
      cells were as low as 20.0 +/- 2.5%, 1.7 +/- 1.7%, and 14.8 +/- 0.9%,
      respectively. Both flow cytometry and confocal microscopy suggested that the
      conjugates could be easily uptaken by A549 cells before the major release of PTX
      moieties. Overall, this work elucidates promising potentials of biodegradable
      zwitterionic polymer-based materials in biomedical applications. STATEMENT OF
      SIGNIFICANCE: The applicability of FDA-approved biodegradable aliphatic
      polyesters has been significantly restricted because they are hydrophobic and
      lack functionalities. Recently zwitterionic polymers have emerged as promising
      hydrophilic biomaterials, but most of the reported zwitterionic polymers are non
      biodegradable. This study reports a novel aliphatic polyester-based zwitterionic
      polymer and the corresponding polymer-drug conjugate. Their aliphatic polyester
      and zwitterionic components provide them with high enzymatic degradability and
      low nonspecific interactions with biomolecules, respectively. While the
      zwitterionic polymer did not show noticeable cytotoxicity, the corresponding
      polymer-anticancer drug conjugate exhibited acid-sensitive sustained drug
      release, remarkable effectiveness in killing cancer cells, as well as the ready
      cellular internalization. This work lays a foundation for the further development
      of synthetic biodegradable zwitterionic polymer-based materials which potentially
      may have broad and significant biomedical applications.

PMID- 29030303
TI  - Electrospun formulations of bevacizumab for sustained release in the eye.
AB  - : Medicines based on vascular endothelial growth factor (VEGF) neutralising
      antibodies such as bevacizumab have revolutionized the treatment of age related
      macular degeneration (AMD), a common blinding disease, and have great potential
      in preventing scarring after surgery or accelerating the healing of corneal
      injuries. However, at present frequent invasive injections are required to
      deliver these antibodies. Such administration is uncomfortable for patients and
      expensive for health service providers. Much effort is thus focused on developing
      dosage forms that can be administered less frequently. Here we use
      electrospinning to prepare a solid form of bevacizumab designed for prolonged
      release while maintaining antibody stability. Electrospun fibers were prepared
      with bevacizumab encapsulated in the core, surrounded by a poly-epsilon
      caprolactone sheath. The fibers were generated using aqueous bevacizumab
      solutions buffered at two different pH values: 6.2 (the pH of the commercial
      product; Fbeva) and 8.3 (the isoelectric point of bevacizumab; FbevaP). The
      fibers had smooth and cylindrical morphologies, with diameters of ca. 500nm. Both
      sets of bevacizumab loaded fibers gave sustained release profiles in an in vitro
      model of the subconjunctival space of the eye. Fbeva displayed first order
      kinetics with t1/2 of 11.4+/-4.4 days, while FbevaP comprises a zero-order
      reservoir type release system with t1/2 of 52.9+/-14.8 days. Both SDS-PAGE and
      surface plasmon resonance demonstrate that the bevacizumab in FbevaP did not
      undergo degradation during fiber fabrication or release. In contrast, the
      antibody released from Fbeva had degraded, and failed to bind to VEGF. Our
      results demonstrate that pH control is crucial to maintain antibody stability
      during the fabrication of core/shell fibers and ensure release of functional
      protein. STATEMENT OF SIGNIFICANCE: Bevacizumab is a potent protein drug which is
      highly effective in the treatment of degenerative conditions in the eye. To be
      effective, frequent injections into the eye are required, which is deeply
      unpleasant for patients and expensive for healthcare providers. Alternative
      methods of administration are thus highly sought after. In our work, we use the
      electrospinning technique to prepare fiber-based formulations loaded with
      bevacizumab. By careful control of the experimental parameters we are able to
      stabilize the protein during processing and ensure a constant rate of release
      over more than two months in vitro. These fibers could thus be used to reduce the
      frequency of dosing required, reducing cost and improving patient outcomes.

PMID- 29030304
TI  - Interaction of cruciferin-based nanoparticles with Caco-2 cells and Caco-2/HT29
      MTX co-cultures.
AB  - : The objective of this work was to assess the potential of Cruciferin/Calcium
      (Cru/Ca) and Cruciferin/Chitosan (Cru/Cs) nanoparticles for oral drug delivery.
      For this purpose, Cru/Ca and Cru/Cs nanoparticles were developed through cold
      gelation of Cruciferin, a major canola protein, and in interaction with calcium
      and chitosan, respectively. The extent and rate of particle uptake in Caco-2
      cells and Caco-2/HT29 co-culture was then evaluated by fluorescence spectroscopy
      as well as flow cytometry. Through pre-incubation of Caco-2 cell monolayer with
      specific endocytosis inhibitors, the mechanism of cell uptake was investigated.
      Our results showed that the uptake of negatively-charged Cru/Ca particles to be
      ~3 times higher than positively-charged Cru/Cs ones by Caco-2 cells. Presence of
      mucus secreted by HT29 cells in their co-culture with Caco-2 had negligible
      influence on the uptake and transport of both particles. In contrast to Cru/Ca
      particles which were dissociated in the simulated gastrointestinal conditions,
      digestion of Cru/Cs particles resulted in 6- and 2-fold increase in the cellular
      uptake and transport of encapsulated coumarin in the latter particles,
      respectively. While the presence of mucus in Caco-2/HT29 co-culture caused 40-50%
      decrease of cellular uptake and transport for coumarin encapsulated in digested
      Cru/Cs particles, it had no significant effect on the cell uptake and transport
      of coumarin associated with Cru/Ca particles after digestion. Energy-dependent
      mechanisms were the dominant mechanism for uptake of both undigested and digested
      particles. Therefore, in Caco-2/HT29 co-culture which closely simulated
      intestinal epithelial cells, undigested Cru/Ca and Cru/Cs particles had the
      ability to penetrate mucus layers, while digested Cru/Cs particles showed
      mucoadhesive property, and digested Cru/Ca particles were dissociated. Our
      results points to a potential for cruciferin based nanoparticles for oral drug
      delivery. STATEMENT OF SIGNIFICANCE: The long-term objective of this research is
      to investigate the potential of edible and safe biopolymer in enhanced oral
      delivery of drugs and/or vaccines. Here, we investigated the potential
      application of nanoparticles based on a protein extracted from Canola seeds,
      i.e., cruciferin, for oral delivery of a model small molecule, i.e., coumarin,
      through cells representing gastrointestinal epithelium, Caco-2 and Caco-2/HT29
      cell monolayer. This study was completed for intact cruciferin nanoparticles and
      cruciferin coated chitosan nanoparticles, before and after digestion with gastric
      or intestine simulating fluids. This comparison was useful to understand the fate
      the cruciferin based particles in digestive mucosal tissues and their potential
      mucoadhesive and/or mucus-penetrating property.

PMID- 29030305
TI  - Entirely S-protected chitosan: A promising mucoadhesive excipient for
      metronidazole vaginal tablets.
AB  - AIM: Synthesis and evaluation of an entirely S-protected chitosan as mucoadhesive
      excipient for vaginal drug delivery. METHODS: N-acetyl-cysteine was linked to 6
      mercaptonicotinamide via disulphide exchange reaction. The obtained ligand, NAC-6
      MNA, was subsequently attached to chitosan by carbodiimide mediated amide bond
      formation in two concentrations. The synthesized S-protected chitosan was
      chemically characterized and mucoadhesive properties and stability against
      oxidation were investigated. Moreover, metronidazole tablets comprising the S
      protected chitosan were evaluated regarding water uptake capacity, disintegration
      behaviour, residence time on vaginal mucosa, release of the encapsulated drug and
      antimicrobial activity. RESULTS: S-protected chitosan displayed 160+/-19 (CS-MNA
      160) and 320+/-38 (CS-MNA-320)umol of ligand per gram of polymer. At pH 4.2, CS
      MNA-160 and CS-MNA-320 showed 5.2-fold and 6.2-fold increase in mucus viscosity
      in comparison to unmodified chitosan (One-way ANOVA, p<.001), whereas, 9.9-fold
      (CS-MNA-160) and 15.6-fold (CS-MNA-320) (One-way ANOVA, p<.001) increase in
      viscosity was measured at pH 6. The S-protected chitosan remained stable against
      oxidation in presence of 0.5%v/v hydrogen peroxide. Metronidazole tablets
      consisting in S-protected chitosan showed prolonged residence time on vaginal
      mucosa and improved water uptake capacity and disintegration time in comparison
      to tablets consisting of unmodified chitosan. Moreover, CS-MNA-320 metronidazole
      tablets displayed prolonged drug release and antimicrobial activity. CONCLUSIONS:
      On the basis of the achieved results, entirely S-protected chitosan represents a
      promising excipient for the development of metronidazole vaginal tablets.
      STATEMENT OF SIGNIFICANCE: S-protected thiomers are polymers modified with thiol
      groups protected by aromatic ligands and characterized by strong mucoadhesive
      properties and high stability against oxidation. Up to date, the entirely S
      protection of thiol groups was achieved via the synthesis of the ligand 2-((2
      amino-2-carboxyethyl)disulfanyl)nicotinic acid) which can be directly bound to
      the backbone of polymers bearing carboxylic moieties as pectin. However, this
      ligand is not suitable for positively charged polymers due to the negative
      charge. In this paper, the synthesis of a suitable ligand for the entirely S
      protection of positively charged polymers is presented. The first entirely S
      protected chitosan was synthesized, characterized and its mucoadhesive properties
      were assessed. Moreover, metronidazole tablets comprising the entirely S
      protected chitosan were developed and evaluated as vaginal drug delivery system.

PMID- 29030306
TI  - Electrospraying of microfluidic encapsulated cells for the fabrication of cell
      laden electrospun hybrid tissue constructs.
AB  - : The fabrication of functional 3D tissues is a major goal in tissue engineering.
      While electrospinning is a promising technique to manufacture a structure
      mimicking the extracellular matrix, cell infiltration into electrospun scaffolds
      remains challenging. The robust and in situ delivery of cells into such
      biomimetic scaffolds would potentially enable the design of tissue engineered
      constructs with spatial control over cellular distribution but often solvents
      employed in the spinning process are problematic due to their high cytotoxicity.
      Herein, microfluidic cell encapsulation is used to establish a temporary
      protection vehicle for the in situ delivery of cells for the development of a
      fibrous, cell-laden hybrid biograft. Therefore a layer-by-layer process is used
      by alternating fiber electrospinning and cell spraying procedures. Both
      encapsulation and subsequent electrospraying of capsules has no negative effect
      on the viability and myogenic differentiation of murine myoblast cells. Propidium
      iodide positive stained cells were analyzed to quantify the amount of dead cells
      and the presence of myosin heavy chain positive cells after the processes was
      shown. Furthermore, encapsulation successfully protects cells from cytotoxic
      solvents (such as dimethylformamide) during in situ delivery of the cells into
      electrospun poly(vinylidene fluoride-co-hexafluoropropylene) scaffolds. The
      resulting cell-populated biografts demonstrate the clear potential of this
      approach in the creation of viable tissue engineering constructs. STATEMENT OF
      SIGNIFICANCE: Infiltration of cells and their controlled spatial distribution
      within fibrous electrospun membranes is a challenging task but allows for the
      development of functional highly organized 3D hybrid tissues. Combining polymer
      electrospinning and cell electrospraying in a layer-by-layer approach is expected
      to overcome current limitations of reduced cell infiltration after traditional
      static seeding. However, organic solvents, used during the electrospinning
      process, impede often major issues due to their high cytotoxicity. Utilizing
      microfluidic encapsulation as a mean to embed cells within a protective polymer
      casing enables the controlled deposition of viable cells without interfering with
      the cellular phenotype. The presented techniques allow for novel cell
      manipulation approaches being significant for enhanced 3D tissue engineering
      based on its versatility in terms of material and cell selection.

PMID- 29030307
TI  - EGFR-targeted multifunctional polymersomal doxorubicin induces selective and
      potent suppression of orthotopic human liver cancer in vivo.
AB  - : Liver cancer is a globally leading malignancy that has a poor five-year
      survival rate of less than 20%. The systemic chemotherapeutics are generally
      ineffective for liver cancers partly due to fast clearance and low tumor uptake.
      Here, we report that GE11 peptide functionalized polymersomal doxorubicin (GE11
      PS-DOX) effectively targets and inhibits epidermal growth factor receptor (EGFR)
      positive SMMC7721 orthotopic human liver tumor xenografts in mice. GE11-PS-DOX
      with a GE11 surface density of 10% displayed a high drug loading of 15.4 wt%, a
      small size of 78 nm, and glutathione-triggered release of DOX. MTT assays, flow
      cytometry and confocal microscopy studies revealed that GE11-PS-DOX mediated
      obviously more efficient DOX delivery into SMMC7721 cells than the non-targeting
      PS-DOX and clinically used liposomal doxorubicin (Lipo-DOX) controls. The in vivo
      studies showed that GE11-PS-DOX had a long circulation time and an extraordinary
      accumulation in the tumors (13.3 %ID/g). Interestingly, GE11-PS-DOX caused much
      better treatment of SMMC7721 orthotopic liver tumor-bearing mice as compared to
      PS-DOX and Lipo-DOX. The mice treated with GE11-PS-DOX (12 mg DOX equiv./kg)
      exhibited a significantly improved survival rate (median survival time: 130 days
      versus 70 and 38 days for PS-DOX at 12 mg DOX equiv./kg and Lipo-DOX at 6 mg DOX
      equiv./kg, respectively) and achieved 50% complete regression. Notably, GE11-PS
      DOX induced obviously lower systemic toxicity than Lipo-DOX. EGFR-targeted
      multifunctional polymersomal doxorubicin with improved efficacy and safety has a
      high potential for treating human liver cancers. STATEMENT OF SIGNIFICANCE: Liver
      cancer is one of the top five leading causes of cancer death worldwide. The
      systemic chemotherapeutics and biotherapeutics generally have a low treatment
      efficacy for hepatocellular carcinoma partly due to fast clearance and/or low
      tumor uptake. Nanomedicines based on biodegradable micelle and polymersomes offer
      a most promising treatment for malignant liver cancers. Their clinical
      effectiveness remains, however, suboptimal owing to issues like inadequate
      systemic stability, low tumor accumulation and selectivity, and poor control over
      drug release. Here we report that GE11 peptide-functionalized, disulfide
      crosslinked multifunctional polymersomal doxorubicin (GE11-PS-DOX) can
      effectively suppress the growth of orthotopic SMMC7721 human liver tumors in nude
      mice. They showed significantly decreased systemic toxicity and improved mouse
      survival rate with 3.4-fold longer median survival time as compared to clinically
      used pegylated liposomal doxorubicin (Lipo-DOX) and achieving 50% complete
      regression. GE11-PS-DOX, based on PEG-PTMC is biodegradable, nontoxic, and easy
      to prepare, appears as a safe, robust, versatile and all-function-in-one
      nanoplatform that has a high potential in targeted chemotherapy of EGFR expressed
      hepatocellular carcinoma.

PMID- 29030308
TI  - Engineering intranasal mRNA vaccines to enhance lymph node trafficking and immune
      responses.
AB  - : Intranasal mRNA vaccination provides immediate immune protection against
      pandemic diseases. Recent studies have shown that diverse forms of
      polyethyleneimine (PEI) have potent mucosal adjuvant activity, which could
      significantly facilitate the delivery of intranasal mRNA vaccines. Nevertheless,
      optimizing the chemical structure of PEI to maximize its adjuvanticity and
      decrease its toxicity remains a challenge. Here we show that the chemical
      structure of PEI strongly influences how well nanocomplexes of PEI and mRNA
      migrate to the lymph nodes and elicit immune responses. Conjugating cyclodextrin
      (CD) with PEI600 or PEI2k yielded CP (CD-PEI) polymers with different CD/PEI
      ratios. We analyzed the delivery efficacy of CP600, CP2k, and PEI25k as
      intranasal mRNA vaccine carriers by evaluating the lymph nodes migration and
      immune responses. Among these polymers, CP2k/mRNA showed significantly higher in
      vitro transfection efficiency, stronger abilities to migrate to lymph nodes and
      stimulate dendritic cells maturation in vivo, which further led to potent humoral
      and cellular immune responses, and showed lower local and systemic toxicity than
      PEI25k/mRNA. These results demonstrate the potential of CD-PEI2k/mRNA nanocomplex
      as a self-adjuvanting vaccine delivery vehicle that traffics to lymph nodes with
      high efficiency. STATEMENT OF SIGNIFICANCE: As we face outbreaks of pandemic
      diseases such as Zika virus, intranasal mRNA vaccination provides instant massive
      protection against highly variant viruses. Various polymer-based delivery systems
      have been successfully applied in intranasal vaccine delivery. However, the
      influence of molecular structure of the polymeric carriers on the lymph node
      trafficking and dendritic cell maturation is seldom studied for intranasal
      vaccination. Therefore, engineering polymer-based vaccine delivery system and
      elucidating the relationship between molecular structure and the intranasal
      delivery efficiency are essential for maximizing the immune responses. We hereby
      construct self-adjuvanting polymer-based intranasal mRNA vaccines to enhance
      lymph node trafficking and further improve immune responses.

PMID- 29030309
TI  - Hearing the Voice of the Resident in Long-Term Care Facilities-An Internationally
      Based Approach to Assessing Quality of Life.
AB  - OBJECTIVES: interRAI launched this study to introduce a set of standardized self
      report measures through which residents of long-term care facilities (LTCFs)
      could describe their quality of life and services. This article reports on the
      international development effort, describing measures relative to privacy, food,
      security, comfort, autonomy, respect, staff responsiveness, relationships with
      staff, friendships, and activities. First, we evaluated these items individually
      and then combined them in summary scales. Second, we examined how the summary
      scales related to whether the residents did or did not say that the LTCFs in
      which they lived felt like home. DESIGN: Cross-sectional self-report surveys by
      residents of LTCFs regarding their quality of life and services.
      SETTING/PARTICIPANTS: Resident self-report data came from 16,017 individuals who
      resided in 355 LTCFs. Of this total, 7113 were from the Flanders region of
      Belgium, 5143 residents were from Canada, and 3358 residents were from the
      eastern and mid-western United States. Smaller data sets were collected from
      facilities in Australia (20), the Czech Republic (72), Estonia (103), Poland
      (118), and South Africa (87). MEASUREMENTS: The interRAI Self-Report Quality of
      Life Survey for LTCFs was used to assess residents' quality of life and services.
      It includes 49 items. Each area of inquiry (eg, autonomy) is represented by
      multiple items; the item sets have been designed to elicit resident responses
      that could range from highly positive to highly negative. Each item has a 5-item
      response set that ranges from "never" to "always." RESULTS: Typically, we scored
      individual items scored based on the 2 most positive categories: "sometimes" and
      "always." When these 2 categories were aggregated, among the more positive items
      were: being alone when wished (83%); decide what clothes to wear (85%); get
      needed services (87%); and treated with dignity by staff (88%). Areas with a less
      positive response included: staff knows resident's life story (30%); resident has
      enjoyable things to do on weekends (32%); resident has people to do things with
      (33%); and resident has friendly conversation with staff (45%). We identified 5
      reliable scales; these scales were positively associated with the resident
      statement that the LTCF felt like home. Finally, international score standards
      were established for the items and scales. CONCLUSIONS: This study establishes a
      set of standardized, self-report items and scales with which to assess the
      quality of life and services for residents in LTCFs. The study also demonstrates
      that these scales are significantly related to resident perception of the home
      like quality of the facilities.

PMID- 29030310
TI  - Dysphagia in Nursing Homes-Results From the NutritionDay Project.
AB  - OBJECTIVES: Dysphagia is a major healthcare problem as it increases the risk of
      malnutrition, dehydration, aspiration pneumonia, and death. The aims of this
      analysis of data from nursing homes (NHs) worldwide were to examine prevalence
      rates of dysphagia, to identify characteristics of residents with dysphagia, and
      to describe which type of nutrition residents with dysphagia receive. DESIGN: One
      day cross-sectional study, repeated in yearly intervals since 2007. SETTING: 926
      NH units from 19 countries. PARTICIPANTS: NH residents participating in the
      nutritionDay between 2007 and 2014, aged 65 years or older, from Europe and North
      America, and with available information on dysphagia. MEASUREMENTS: Data on
      resident and unit level were collected on nutritionDay by local nursing staff
      using standardized questionnaires. Residents' nutritional status, nutritional
      intake, general residents' characteristics, and unit characteristics were of
      interest as potential predictors of dysphagia (no vs yes). Univariable
      generalized estimating equations were performed for all variables, and
      significant predictors (P < .01) included in a multivariable analysis.
      Nutritional strategies (type of diet, use of oral nutritional supplements, tube
      feeding, and parenteral nutrition) are described for residents with and without
      dysphagia. RESULTS: Dysphagia was reported in 13.4% of the 23,549 residents
      included, with great variation in the prevalence rates between participating
      countries. Twelve variables of 23 remained in the multivariable model [area under
      the receiver operating curve = 0.898; 95% confidence interval (CI) 0.892-0.904; P
      < .001]. Residents who were not able to eat lunch orally on nutritionDay were
      14.90 [odds ratio (OR); 95% CI 9.61-23.11] times more likely to have dysphagia
      compared with residents who ate everything. ORs of dysphagia were higher for
      residents with chewing problems (OR 10.48; 95% CI 8.98-12.23), immobile (OR 5.10,
      95% CI 4.25-6.11) and partially mobile residents (OR 1.94; 95% CI 1.64-2.29)
      compared to mobile residents, and residents with severe cognitive impairment (OR
      1.99; 95% CI 1.64-2.42). Poor nutritional status, digestive diseases, neurologic
      diseases, dehydration, and use of antibiotics were also related to a higher risk
      of dysphagia. The most common nutritional strategy for residents with dysphagia
      was providing texture-modified diet (42.5%) followed by normal diet (28.2%). One
      quarter of residents with dysphagia received oral nutritional supplements
      additionally, 7.4% of residents with dysphagia received tube feeding exclusively,
      and 8.0% in combination with oral nutrition. CONCLUSIONS: This analysis of NHs
      participating in the nutritionDay provides important insight into the current
      awareness of dysphagia, associated factors, and nutritional strategies. Residents
      who were unable to eat orally, malnourished, or dehydrated suffered more often
      from dysphagia, which substantiates the challenges of providing safe and adequate
      nutrition for residents with dysphagia. Adequacy and efficiency of different
      nutritional strategies need to be clarified in future studies.

PMID- 29030311
TI  - Potential transmission opportunity of CTX-M-producing Escherichia coli on a large
      scale chicken farm in Vietnam.
AB  - OBJECTIVES: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli
      have disseminated worldwide. This study investigated blaCTX-M-positive E. coli on
      a large-scale Vietnamese chicken farm and analysed whether there was any
      difference in prevalence and molecular characteristics of blaCTX-M-positive E.
      coli between the farm and the Vietnamese community. METHODS: Faecal samples were
      collected from 24 human individuals and 38 chickens from the large-scale chicken
      farm as well as 51 humans and 36 chickens from the community. All samples were
      collected between June 2013 and June 2014 in Bavi Province in the Red River Delta
      region of Vietnam. Molecular characterisation of CTX-M-producing E. coli and
      genetic relatedness among the isolates were evaluated by conventional typing
      methods. Antimicrobial susceptibility of the isolates was evaluated by the disk
      diffusion method. RESULTS: The prevalence of blaCTX-M-positive E. coli was 83.3%,
      71.1%, 54.9% and 13.9% in farm workers, farm chickens, community individuals and
      community backyard chickens, respectively. On average, blaCTX-M-positive E. coli
      isolates from farm chickens were resistant to 8.3 different antibiotics. The
      average number of detected aminoglycoside-modifying enzyme genes (3.4 genes) and
      the detection rate of the plasmid-mediated colistin resistance gene mcr-1 (33.3%)
      were higher in blaCTX-M-positive E. coli isolated from farm chickens compared
      with other sampling groups. In addition, two types of indistinguishable pulsed
      field gel electrophoresis (PFGE) patterns were observed in six blaCTX-M-65
      positive E. coli and three blaCTX-M-55-positive E. coli from farm chickens.
      CONCLUSIONS: These results suggest a more frequent transmission opportunity of
      blaCTX-M-positive E. coli on the large-scale Vietnamese chicken farm.

PMID- 29030312
TI  - Antimicrobial resistance of Enterococcus spp. isolated from Thai fermented pork
      in Chiang Rai Province, Thailand.
AB  - OBJECTIVES: The aim of this study was to evaluate the prevalence of antimicrobial
      resistant phenotypes and genes of Enterococcus spp. in order to explore the range
      of resistance profiles from Thai traditional fermented pork. METHODS: A total of
      120 Thai fermented pork specimens were collected in Chiang Rai, Thailand.
      Antimicrobial resistance among isolated enterococci to 11 antimicrobial agents
      was determined by the agar disk diffusion method. Antibiotic resistance genes
      from resistant phenotypes and virulence genes were observed. RESULTS: A total of
      119 enterococci were found contaminating the collected samples. The most
      prevalent species was Enterococcus faecalis (68.9%), followed by Enterococcus
      hirae (16.0%), Enterococcus faecium (13.4%) and Enterococcus gallinarum (1.7%).
      The highest percentage of resistance was to ciprofloxacin (97.5%), followed by
      erythromycin (78.2%) and tetracycline (67.2%), whilst high-level gentamicin- and
      streptomycin-resistant isolates were of lower frequency (7.6% and 22.7%,
      respectively). All isolates were susceptible to the clinically important agents
      vancomycin and teicoplanin. Overall, a relatively high frequency of multidrug
      resistant (MDR) enterococci was observed (76.2%). Antimicrobial-resistant
      phenotypes were found to carry aacA-aphD, addE, erm(B), mefA/E, cat, tet(L) and
      tet(M) resistance genes. Virulence genes were also evaluated and the gelE gene
      was found to be the most common (37.8%). CONCLUSIONS: These data highlight the
      importance of MDR enterococci in fermented pork in Thailand. This is the first
      report to detect the unusual species E. hirae carrying the mefA/E macrolide
      resistance gene. These clinically important and unusual enterococci isolates from
      Thai fermented pork could be a source of transferable resistance genes to other
      bacteria.

PMID- 29030313
TI  - First description of the emergence of Enterobacter asburiae producing IMI-2
      carbapenemase in the Czech Republic.

PMID- 29030314
TI  - Distribution of Ixodes ricinus ticks and prevalence of tick-borne encephalitis
      virus among questing ticks in the Arctic Circle region of northern Norway.
AB  - This study investigated the geographical distribution of Ixodes ricinus and
      prevalence of the tick-borne encephalitis virus (TBEV) in northern Norway.
      Flagging for questing I. ricinus ticks was performed in areas ranging from Vikna
      in Nord-Trondelag County, located 190km south of the Arctic Circle (66.3 degrees
      N), to Steigen in Nordland County, located 155km north of the Arctic Circle. We
      found that ticks were abundant in both Vikna (64.5 degrees N) and Bronnoy (65.1
      degrees N). Only a few ticks were found at locations ~66 degrees N, and no ticks
      were found at several locations up to 67.5 degrees N. Real-time PCR (RT-PCR)
      analyses of the collected ticks (nymphs and adults) for the presence of TBEV
      revealed a low prevalence (0.1%) of TBEV among the nymphs collected in Vikna,
      while a prevalence of 0% to 3% was found among nymphs collected at five locations
      in Bronnoy. Adult ticks collected in Vikna and Bronnoy had higher rates of TBEV
      infection (8.6% and 0%-9.0%, respectively) than the nymphs. No evidence of TBEV
      was found in the few ticks collected further north of Bronnoy. This is the first
      report of TBEV being detected at locations up to 65.1 degrees N. It remains to be
      verified whether viable populations of I. ricinus exist at locations north of 66
      degrees N. Future studies are warranted to increase our knowledge concerning tick
      distribution, tick abundance, and tick-borne pathogens in northern Norway.

PMID- 29030315
TI  - Natural history of Ixodes affinis in Virginia.
AB  - The ixodid tick species Ixodes affinis is expanding its range northward, changing
      the tick community population dynamics in the Mid-Atlantic United States. We
      present five years of surveillance on newly established populations of I. affinis
      throughout southeastern Virginia and discuss the habitat and host associations of
      I. affinis in this northernmost extent of its range. We found that I. affinis
      populations tend to persist once they are established, and populations tend to
      increase as ecological succession progresses, provided a vegetated understory
      persists. Populations of I. affinis were never found in the smallest habitat
      fragments or in xeric dune habitats, and the highest densities of I. affinis were
      found in mixed pine-hardwood forests with an herbaceous understory. We also
      document several new mammalian hosts for I. affinis, including house mice (Mus
      musculus) and coyotes (Canis latrans) and discuss how these hosts may facilitate
      the continued dispersal of I. affinis and the maintenance of these newly
      established populations.

PMID- 29030316
TI  - Post-molting development of wind-elicited escape behavior in the cricket.
AB  - Arthropods including insects grow through several developmental stages by
      molting. The abrupt changes in their body size and morphology accompanying the
      molting are responsible for the developmental changes in behavior. While in
      holometabolous insects, larval behaviors are transformed into adult-specific
      behaviors with drastic changes in nervous system during the pupal stage,
      hemimetabolous insects preserve most innate behaviors whole life long, which
      allow us to trace the maturation process of preserved behaviors after the changes
      in body. Wind-elicited escape behavior is one of these behaviors and mediated by
      cercal system, which is a mechanosensory organ equipped by all stages of nymph in
      orthopteran insects like crickets. However, the maturation process of the escape
      behavior after the molt is unclear. In this study, we examined time-series of
      changes in the wind-elicited escape behavior just after the imaginal molt in the
      cricket. The locomotor activities are developed over the elapsed time, and
      matured 24h after the molt. In contrast, a stimulus-angle dependency of moving
      direction was unchanged over time, meaning that the cercal sensory system
      detecting airflow direction was workable immediately after the molt, independent
      from the behavioral maturation. The post-molting development of the wind-elicited
      behavior was considered to result not simply from maturation of the exoskeleton
      or musculature because the escape response to heat-shock stimulus did not change
      after the molt. No effect of a temporal immobilization after the imaginal molt on
      the maturation of the wind-elicited behavior also implies that the maturation may
      be innately programmed without experience of locomotion.

PMID- 29030317
TI  - Biopsy Core Features are Poor Predictors of Adverse Pathology in Men with Grade
      Group 1 Prostate Cancer.
AB  - PURPOSE: Active surveillance is often restricted to patients with low risk
      prostate cancer who have 3 or fewer positive cores. We aimed to identify
      predictors of adverse pathology results for low risk prostate cancer treated with
      radical prostatectomy and determine whether a threshold number of positive cores
      could help the decision process for active surveillance. MATERIALS AND METHODS: A
      total of 3,359 men with low risk prostate cancer underwent radical prostatectomy
      between January 2000 and August 2016. We analyzed the relationship between biopsy
      core features and adverse pathology at radical prostatectomy, defined as Grade
      Group 3 or greater, seminal vesicle invasion or lymph node involvement. RESULTS:
      Of the 171 cases (5.1%) with adverse pathology findings at radical prostatectomy
      144 (4.3%) were upgraded to Grade Group 3 or greater, 31 (0.9%) had seminal
      vesicle invasion and 15 (0.4%) had lymph node involvement. Prostate specific
      antigen and patient age were the only predictors of adverse pathology results.
      There was no significant association with the number of positive cores, the total
      mm of cancer or the maximum percent of cancer in any core. When we expanded the
      definition of adverse pathology to include Grade Group 2 and extraprostatic
      extension, the association between core features and outcome was statistically
      significant but clinically weak, and with no evidence of threshold effects.
      CONCLUSIONS: There is little basis for excluding patients with otherwise low risk
      prostate cancer on biopsy from active surveillance based on criteria such as the
      number of positive cores or the maximum cancer involvement of biopsy cores.

PMID- 29030318
TI  - The Association between Mortality and Distance to Treatment Facility in Patients
      with Muscle Invasive Bladder Cancer.
AB  - PURPOSE: Regionalization of bladder cancer treatment is suggested to improve
      quality of care. As an unintended consequence some patients travel farther for
      care with unknown implications on outcomes. We characterized the relationship
      between distance and overall mortality in patients with invasive bladder cancer
      and those who underwent radical cystectomy. MATERIALS AND METHODS: We performed a
      retrospective cohort study using NCDB (National Cancer Database) from 2004 to
      2012 to identify patients with muscle invasive bladder cancer (cT2a-T4 N0 M0). We
      also extracted a subgroup of patients who underwent radical cystectomy.
      Multivariate Cox proportional hazards and multinomial logistic regression
      analyses were performed in each group, controlling for demographic, clinical,
      hospital and geographic factors. RESULTS: For 34,729 patients with muscle
      invasive bladder cancer traveling farther for treatment was associated with a
      lower probability of overall mortality (referent less than 12.5 miles, 12.5 to
      49.9 miles HR 0.96, 95% CI 0.92-0.99 and 50 to 249.9 miles HR 0.91, 95% CI 0.86
      0.96). This was significant for patients with cT2 disease and those treated at
      academic centers (p <=0.05). For 11,059 patients who underwent radical cystectomy
      this trend did not reach significance. However, longer distance was associated
      with surgery at a high volume institution and receipt of neoadjuvant chemotherapy
      (each p <0.001). CONCLUSIONS: Patients who traveled farther for bladder cancer
      treatment did not experience inferior survival outcomes and traveling to academic
      institutions was associated with reduced mortality. For patients who undergo
      cystectomy this relationship was equivocal, although longer distance was
      associated with receiving neoadjuvant chemotherapy or surgery at a high volume
      facility. These findings may reflect a complex association of regionalization of
      bladder cancer care with patient individual health and health care seeking
      behavior.

PMID- 29030319
TI  - Coordination of different ligands to copper(II) and cobalt(III) metal centers
      enhances Zika virus and dengue virus loads in both arthropod cells and human
      keratinocytes.
AB  - : Trace elements such as copper and cobalt have been associated with virus-host
      interactions. However, studies to show the effect of conjugation of copper(II) or
      cobalt(III) metal centers to thiosemicarbazone ligand(s) derived from either food
      additives or mosquito repellent such as 2-acetylethiazole or citral,
      respectively, on Zika virus (ZIKV) or dengue virus (serotype 2; DENV2) infections
      have not been explored. In this study, we show that four compounds comprising of
      thiosemicarbazone ligand derived from 2-acetylethiazole viz., (E)-N-ethyl-2-[1
      (thiazol-2-yl)ethylidene]hydrazinecarbothioamide (acetylethTSC) (compound 1), a
      copper(II) complex with acetylethTSC as a ligand (compound 2), a
      thiosemicarbazone ligand-derived from citral (compound 3) and a cobalt(III)
      complex with a citral-thiosemicarbazone ligand (compound 4) increased DENV2 and
      ZIKV replication in both mosquito C6/36 cells and human keratinocytes (HaCaT
      cells). Treatment of both cell lines with compounds 2 or 4 showed increased
      dengue viral titers at all three tested doses. Enhanced dengue viral plaque
      formation was also noted at the tested dose of 100MUM, suggesting higher
      production of infectious viral particles. Treatment with the compounds 2 or 4
      enhanced ZIKV and DENV2 RNA levels in HeLa cell line and primary cultures of
      mouse bone marrow derived dendritic cells. Also, pre- or post treatments with
      conjugated compounds 2 or 4 showed higher loads of ZIKV or DENV2 envelope (E)
      protein in HaCaT cells. No changes in loads of E-protein were found in ZIKV
      infected C6/36 cells, when compounds were treated after infection. In addition,
      we tested bis(1,10-phenanthroline)copper(II) chloride ([Cu(phen)2]Cl2, (compound
      5) and tris(1,10-phenanthroline)cobalt(III) chloride ([Co(phen)3]Cl3, (compound
      6) that also showed enhanced DENV2 loads. Also, we found that copper(II) chloride
      dehydrate (CuCl2.2H2O) or cobalt(II) chloride hexahydrate (CoCl2.6H2O) alone had
      no effects as "free" cations. Taken together, these findings suggest that use of
      Cu(II) or Co(III) conjugation to organic compounds, in insect repellents and/or
      food additives could enhance DENV2/ZIKV loads in human cells and perhaps induce
      pathogenesis in infected individuals or individuals pre-exposed to such
      conjugated complexes. IMPORTANCE: Mosquito-borne diseases are of great concern to
      the mankind. Use of chemicals/repellents against mosquito bites and transmission
      of microbes has been the topic of interest for many years. Here, we show that
      thiosemicarbazone ligand(s) derived from 2-acetylethiazole or citral or 1,10
      phenanthroline upon conjugation with copper(II) or cobalt(III) metal centers
      enhances dengue virus (serotype 2; DENV2) and/or Zika virus (ZIKV) infections in
      mosquito, mouse and human cells. Enhanced ZIKV/DENV2 capsid mRNA or envelope
      protein loads were evident in mosquito cells and human keratinocytes, when
      treated with compounds before/after infections. Also, treatment with copper(II)
      or cobalt(III) conjugated compounds increased viral titers and number of plaque
      formations. These studies suggest that conjugation of compounds in
      repellents/essential oils/natural products/food additives with copper(II) or
      cobalt(III) metal centers may not be safe, especially in tropical and subtropical
      places, where several dengue infection cases and deaths are reported annually or
      in places with increased ZIKV caused microcephaly.

PMID- 29030320
TI  - ATP released from astrocytes modulates action potential threshold and spontaneous
      excitatory postsynaptic currents in the neonatal rat prefrontal cortex.
AB  - Maternal immune activation during pregnancy is a risk factor for
      neurodevelopmental disorders, such as schizophrenia; however, a full mechanistic
      understanding has yet to be established. The activity of a transient cell
      population, the subplate neurons, is critical for the development of cortical
      inhibition and functional thalamocortical connections. Sensitivity of these cells
      to factors released during inflammation, therefore, may offer a link between
      maternal immune activation and the aberrant cortical development underlying some
      neuropsychiatric disorders. An elevated extracellular ATP concentration is
      associated with inflammation and has been shown to have an effect on neuronal
      activity. Here, we investigated the effect of ATP on the electrophysiological
      properties of subplate neurons. Exogenous ATP increased the frequency and
      amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) at micromolar
      concentrations. Further, ATP released by astrocytes activated by the PAR-1
      agonist, TFLLR-NH2, also increased the amplitude and frequency of sEPSCs in
      subplate neurons. The electrophysiological properties of subplate neurons
      recorded from prefrontal cortical (PFC) slices from neonatal rats were also
      disrupted in a maternal immune activation rat model of schizophrenia, with a
      suramin-sensitive increase in frequency and amplitude of sEPSCs. An alternative
      neurodevelopmental rat model of schizophrenia, MAM-E17, which did not rely on
      maternal immune activation, however, showed no change in subplate neuron
      activity. Both models were validated with behavioral assays, showing
      schizophrenia-like endophenotypes in young adulthood. The purinergic modulation
      of subplate neuron activity offers a potential explanatory link between maternal
      immune activation and disruptions in cortical development that lead to the
      emergence of neuropsychiatric disorders.

PMID- 29030321
TI  - Destination specific risks of acquisition of notifiable food- and waterborne
      infections or sexually transmitted infections among Finnish international
      travellers, 1995-2015.
AB  - BACKGROUND: Overnight international travels made by Finns more than doubled
      during 1995-2015. To estimate risks and observe trends of travel-related
      notifiable sexually transmitted and food- and water-borne infections (STIs and
      FWIs) among travellers, we analysed national reports of gonorrhoea, syphilis,
      hepatitis A, shigellosis, campylobacteriosis and salmonellosis cases and related
      them to travel statistics. METHOD: Cases notified as travel-related to the
      Finnish infectious diseases register were used as numerators and overnight stays
      of Statistics Finland surveys as denominator. We calculated overall risks (per
      100,000 travellers) and assessed trends (using regression model) in various
      geographic regions. RESULTS: Of all travel-related cases during 1995-2015, 2304
      were STIs and 70,929 FWIs. During 2012-2015, Asia-Oceania showed highest risk
      estimates for gonorrhoea (11.0; 95%CI, 9.5-13), syphilis (1.4; 0.93-2.1),
      salmonellosis (157; 151-164), and campylobacteriosis (135; 129-141), and Africa
      for hepatitis A (4.5; 2.5-7.9), and shigellosis (35; 28-43). When evaluating at
      country level, the highest risks of infections was found in Thailand, except for
      hepatitis A ranking Hungary the first. During 2000-2011, significantly decreasing
      trends occurred for most FWIs particularly in the European regions and for STIs
      in Russia-Baltics. CONCLUSIONS: Our findings can be used in targeting pre-travel
      advice, which should also cover those visiting Thailand or European hepatitis A
      risk areas.

PMID- 29030322
TI  - Pain Affects Visual Orientation: an Eye-Tracking Study.
AB  - : Because of its unique evolutionary relevance, it is understood that pain
      automatically attracts attention. So far, such attentional bias has mainly been
      shown for pain-related stimuli whereas little is known about shifts in
      attentional focus after actual painful stimulation. This study investigated
      attentional shifts by assessing eye movements into the direction of painful
      stimulation. Healthy participants were presented either a blank screen or a
      picture showing a natural scene while painful electrical stimuli were applied to
      the left or right hand. In general, painful stimulation reduced exploratory
      behavior as reflected by less and slower saccades as well as fewer and longer
      fixations. Painful stimulation on the right hand induced a rightward bias (ie,
      increased initial saccades, total number and duration of fixations to the right
      hemifield of the screen). Pain applied to the left hand as well as no pain
      induced a leftward bias that was largest for the direction of first saccades.
      These findings are in line with previous observations of attentional biases
      toward pain-related information and highlight eye tracking as a valuable tool to
      assess involuntary attentional consequences of pain. Future studies are needed to
      investigate how the observed changes in eye movements relate to pain-induced
      changes in perception and cognition. PERSPECTIVE: The study investigated pain
      induced attentional shifts in terms of reflexive eye movements. This attention
      capturing quality of pain should be examined in chronic pain conditions because
      it might contribute to the cognitive impairments often observed in chronic pain
      patients.

PMID- 29030323
TI  - Gender and the Association between Long-Term Prescription Opioid Use and New
      Onset Depression.
AB  - : Women have a higher prevalence of chronic noncancer pain conditions and report
      more severe pain, yet, it is not known if the association between long-term
      opioid analgesic use (OAU) and risk of a new depression episode (NDE) differs
      according to gender. We analyzed patient data from the Veterans Health
      Administration (VHA; 2000-2012; n = 70,997) and a large private-sector health
      care organization (2003-2012; n = 22,981) to determine whether long-term OAU and
      risk of NDE differed according to gender. Patients were free of depression and
      OAU for 2 years before baseline. OAU duration was defined as 1 to 30, 31 to 90
      and more than 90 days, and NDE was defined according to International
      Classification of Diseases, Ninth Revision codes. Gender-stratified Cox
      proportional hazard models were used to estimate hazard ratios (HRs). Propensity
      scores and subsequent inverse probability of treatment weighting controlled for
      confounding. In the VHA, more than 90 compared with 1- to 30-day OAU was more
      strongly associated with NDE among female than male patients (female: HR = 1.79
      [95% confidence interval (CI), 1.45-2.22] vs male HR = 1.25 [95% CI, 1.16-1.34],
      P = .002). In private sector patients, there was no gender difference in the
      association between more than 90-day OAU and NDE (female HR = 1.97 [95% CI, 1.64
      2.37] vs male HR = 1.99 [95% CI, 1.44-2.74]). Risk of NDE after long-term OAU is
      similar in men and women in private sector patients but may differ for VHA
      patients. Future prospective studies are needed to identify mechanisms for the
      association between longer OAU and NDE. PERSPECTIVE: Existing research is mixed
      regarding gender differences in outcomes after long-term prescription opioid use.
      This study found both genders have increased risk of an NDE after more than 90
      days of opioid use. Women and men may benefit from closer monitoring of mood
      associated with chronic opioid use.

PMID- 29030324
TI  - Exploring the Therapeutic Affordances of Self-Harm Online Support Communities: An
      Online Survey of Members.
AB  - BACKGROUND: A growing number of online communities have been established to
      support those who self-harm. However, little is known about the therapeutic
      affordances arising from engagement with these communities and resulting
      outcomes. OBJECTIVE: The aim of this study was to explore the presence of
      therapeutic affordances as reported by members of self-harm online support
      communities. METHODS: In total, 94 respondents (aged 13-63 years, mean=23.5
      years; 94% female) completed an online survey exploring their experiences of
      engaging with a self-harm online support community. Respondents varied in terms
      of how long they had been accessing an online community, with 22% (21/94)
      accessing less than 1 year, 39% (37/94) 1 to 2 years, 14% (13/94) 2 to 3 years,
      and 24.5% (23/94) more than 3 years. Responses were analyzed using deductive
      thematic analysis. RESULTS: The results of our analysis describe each of the five
      therapeutic affordances that were present in the data, namely (1) connection, the
      ability to make contact with others who self-harm for the purposes of mutual
      support and in so doing reduce feelings of loneliness and isolation; (2)
      adaptation, that is, how use of online support varies in relation to the personal
      circumstances of the individual user; (3) exploration, that is, the ability to
      learn about self-harm and learn about strategies to reduce or stop self-harming
      behavior; (4) narration, that is, the ability to share experiences, as well as
      read about the experiences of others; and (5) self-presentation, that is, how and
      what users present about themselves to others in the online community.
      CONCLUSIONS: Our findings suggest that engagement with self-harm online support
      communities may confer a range of therapeutic benefits for some users, which may
      serve to minimize the psychosocial burden of self-harm and promote positive
      coping strategies. In addition, the online nature of the support available may be
      helpful to those who are unable to access face-to-face support.

PMID- 29030325
TI  - ADHD: Is There an App for That? A Suitability Assessment of Apps for the Parents
      of Children and Young People With ADHD.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a highly comorbid
      disorder that can impact significantly on the individual and their family. ADHD
      is managed via pharmacological and nonpharmacological interventions. Parents also
      gain support from parent support groups, which may include chat rooms, as well as
      face-to-face meetings. With the growth of technology use over recent years,
      parents have access to more resources that ever before. A number of mobile apps
      have been developed to help parents manage ADHD in their children and young
      people. Unfortunately many of these apps are not evidence-based, and little is
      known of their suitability for the parents or whether they are helpful in ADHD
      management. OBJECTIVE: The aim of this study was to explore the (1) parents'
      views of the suitability of the top ten listed apps for parents of children and
      young people with ADHD and (2) the views of clinicians that work with them on the
      suitability and value of the apps. METHODS: The top 10 listed apps specifically
      targeted toward the parents of children and young people with ADHD were
      identified via the Google Play (n=5) and iTunes store (n=5). Interviews were then
      undertaken with 7 parents of children or young people with ADHD and 6 clinicians
      who specialize in working with this population to explore their opinions of the
      10 apps identified and what they believe the key components are for apps to be
      suitable and valuable for this population. RESULTS: Four themes emerged from
      clinician and parent interviews: (1) the importance of relating to the app, (2)
      apps that address ADHD-related difficulties, (3) how the apps can affect family
      relationships, and (4) apps as an educational tool. Two additional themes emerged
      from the clinician interviews alone: monitoring ADHD symptoms and that apps
      should be practical. Parents also identified an additional theme: the importance
      of the technology. Overall, the characteristics of the current top 10 listed apps
      did not appear to match well to the views of our sample. CONCLUSIONS: Findings
      suggest that these apps may not fully meet the complex needs of this parent
      population. Further research is required to explore the value of apps with this
      population and how they can be tailored to their very specific needs.

PMID- 29030326
TI  - Consumer Health-Related Activities on Social Media: Exploratory Study.
AB  - BACKGROUND: Although a number of studies have investigated how consumers use
      social media for health-related purposes, there is a paucity of studies in the
      Australian context. OBJECTIVE: This study aimed to explore how Australian
      consumers used social media for health-related purposes, specifically how they
      identified social media platforms, which were used, and which health-related
      activities commonly took place. METHODS: A total of 5 focus groups (n=36
      participants), each lasting 60 to 90 minutes, were conducted in the Sydney
      metropolitan area. The group discussions were audiorecorded and transcribed
      verbatim. The transcripts were coded line-by-line and thematically analyzed.
      RESULTS: Participants used general search engines to locate health-related social
      media platforms. They accessed a wide range of social media on a daily basis,
      using several electronic devices (in particular, mobile phones). Although privacy
      was a concern, it did not prevent consumers from fully engaging in social media
      for health-related purposes. Blogs were used to learn from other people's
      experiences with the same condition. Facebook allowed consumers to follow health
      related pages and to participate in disease-specific group discussions. Wikipedia
      was used for factual information about diseases and treatments. YouTube was
      accessed to learn about medical procedures such as surgery. No participant
      reported editing or contributing to Wikipedia or posting YouTube videos related
      to health topics. Twitter was rarely used for health-related purposes. Social
      media allowed consumers to obtain and provide disease and treatment-related
      information and social and emotional support for those living with the same
      condition. Most considered their participation as observational, but some also
      contributed (eg, responded to people's questions). CONCLUSIONS: Participants used
      a wide range of social media for health-related purposes. Medical information
      exchange (eg, disease and treatment) and social and emotional support were the
      cornerstones of their online activities. Social media appears to be used as a key
      tool to support disease self-management.

PMID- 29030328
TI  - Studying Acute Coronary Syndrome Through the World Wide Web: Experiences and
      Lessons.
AB  - This study details my viewpoint on the experiences, lessons, and assessments of
      conducting a national study on care-seeking behavior for heart attack in the
      United States utilizing the World Wide Web. The Yale Heart Study (YHS) was funded
      by the National Heart, Lung, and Blood Institute (NHLBI) of the National
      Institutes of Health (NIH). Grounded on two prior studies, the YHS combined a Web
      based interview survey instrument; ads placed on the Internet; flyers and posters
      in public libraries, senior centers, and rehabilitation centers; information on
      chat rooms; a viral marketing strategy; and print ads to attract potential
      participants to share their heart attack experiences. Along the way, the grant
      was transferred from Ohio State University (OSU) to Yale University, and
      significant administrative, information technology, and personnel challenges
      ensued that materially delayed the study's execution. Overall, the use of the
      Internet to collect data on care-seeking behavior is very time consuming and
      emergent. The cost of using the Web was approximately 31% less expensive than
      that of face-to-face interviews. However, the quality of the data may have
      suffered because of the absence of some data compared with interviewing
      participants. Yet the representativeness of the 1154 usable surveys appears good,
      with the exception of a dearth of African American participants.

PMID- 29030327
TI  - The Effectiveness of eHealth Technologies on Weight Management in Pregnant and
      Postpartum Women: Systematic Review and Meta-Analysis.
AB  - BACKGROUND: The emergence and utilization of electronic health (eHealth)
      technologies has increased in a variety of health interventions. Exploiting the
      real-time advantages offered by mobile technologies during and after pregnancy
      has the potential to empower women and encourage behaviors that may improve
      maternal and child health. OBJECTIVE: The objective of this study was to assess
      the effectiveness of eHealth technologies for weight management during pregnancy
      and the postpartum period and to review the efficacy of eHealth technologies on
      health behaviors, specifically nutrition and physical activity. METHODS: A
      systematic search was conducted of the following databases: MEDLINE, EMBASE,
      Cochrane database of systematic reviews (CDSR), Cochrane central register of
      controlled trials (CENTRAL), CINAHL (Cumulative Index to Nursing and Allied
      Health Literature), and PsycINFO. The search included studies published from 1990
      to July 5, 2016. All relevant primary studies that involved randomized controlled
      trials (RCTs), non-RCTs, before-and-after studies, historically controlled
      studies, and pilot studies were included. The study population was adult women of
      childbearing age either during pregnancy or the postpartum period. eHealth weight
      management intervention studies targeting physical activity, nutrition, or both,
      over a minimum 3-month period were included. Titles and abstracts, as well as
      full-text screening were conducted. Study quality was assessed using Cochrane's
      risk of bias tool. Data extraction was completed by a single reviewer, which was
      then verified by a second independent reviewer. Results were meta-analyzed to
      calculate pooled estimates of the effect, wherever possible. RESULTS: Overall,
      1787 and 176 citations were reviewed at the abstract and full-text screening
      stages, respectively. A total of 10 studies met the inclusion criteria ranging
      from high to low risk of bias. Pooled estimates from studies of the effect for
      postpartum women resulted in a significant reduction in weight (-2.55 kg, 95% CI 
      3.81 to -1.28) after 3 to 12 months and six studies found a nonsignificant
      reduction in weight gain for pregnant women (-1.62 kg, 95% CI -3.57 to 0.33) at
      approximately 40 weeks. CONCLUSIONS: This review found evidence for benefits of
      eHealth technologies on weight management in postpartum women only. Further
      research is still needed regarding the use of these technologies during and after
      pregnancy.

PMID- 29030331
TI  - On OX40 and PD-1 Combination: Why Should OX40 Be First in Sequence?
AB  - The larger fraction of patients treated with immune checkpoint inhibitors remain
      nonresponding eventually. Combination of checkpoint inhibitor and costimulatory
      antibodies is thought additive, but for such effect, they may require to be given
      in the right sequence. Clin Cancer Res; 23(20); 5999-6001. (c)2017 AACRSee
      related article by Messenheimer et al., p. 6165.

PMID- 29030332
TI  - Genomics of Immunotherapy-Associated Hyperprogressors-Letter.

PMID- 29030333
TI  - Genomics of Immunotherapy-Associated Hyperprogressors-Response.

PMID- 29030329
TI  - Effect of a Website That Presents Patients' Experiences on Self-Efficacy and
      Patient Competence of Colorectal Cancer Patients: Web-Based Randomized Controlled
      Trial.
AB  - BACKGROUND: Patients often seek other patients' experiences with the disease. The
      Internet provides a wide range of opportunities to share and learn about other
      people's health and illness experiences via blogs or patient-initiated online
      discussion groups. There also exists a range of medical information devices that
      include experiential patient information. However, there are serious concerns
      about the use of such experiential information because narratives of others may
      be powerful and pervasive tools that may hinder informed decision making. The
      international research network DIPEx (Database of Individual Patients'
      Experiences) aims to provide scientifically based online information on people's
      experiences with health and illness to fulfill patients' needs for experiential
      information, while ensuring that the presented information includes a wide
      variety of possible experiences. OBJECTIVE: The aim is to evaluate the colorectal
      cancer module of the German DIPEx website krankheitserfahrungen.de with regard to
      self-efficacy for coping with cancer and patient competence. METHODS: In 2015, a
      Web-based randomized controlled trial was conducted using a two-group between
      subjects design and repeated measures. The study sample consisted of individuals
      who had been diagnosed with colorectal cancer within the past 3 years or who had
      metastasis or recurrent disease. Outcome measures included self-efficacy for
      coping with cancer and patient competence. Participants were randomly assigned to
      either an intervention group that had immediate access to the colorectal cancer
      module for 2 weeks or to a waiting list control group. Outcome criteria were
      measured at baseline before randomization and at 2 weeks and 6 weeks. RESULTS:
      The study randomized 212 persons. On average, participants were 54 (SD 11.1)
      years old, 58.8% (124/211) were female, and 73.6% (156/212) had read or heard
      stories of other patients online before entering the study, thus excluding any
      influence of the colorectal cancer module on krankheitserfahrungen.de. No
      intervention effects were found at 2 and 6 weeks after baseline. CONCLUSIONS: The
      results of this study do not support the hypothesis that the website studied may
      increase self-efficacy for coping with cancer or patient competencies such as
      self-regulation or managing emotional distress. Possible explanations may involve
      characteristics of the website itself, its use by participants, or methodological
      reasons. Future studies aimed at evaluating potential effects of websites
      providing patient experiences on the basis of methodological principles such as
      those of DIPEx might profit from extending the range of outcome measures, from
      including additional measures of website usage behavior and users' motivation,
      and from expanding concepts, such as patient competency to include items that
      more directly reflect patients' perceived effects of using such a website. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT02157454;
      https://clinicaltrials.gov/ct2/show/NCT02157454 (Archived by WebCite at
      http://www.webcitation.org/6syrvwXxi).

PMID- 29030334
TI  - Individualized Pazopanib Dosing-Letter.

PMID- 29030336
TI  - Global project to map drug resistance and tackle "superbugs" is launched.

PMID- 29030338
TI  - Estrogen replacement attenuates stress-induced pressor responses through
      vasorelaxation via beta2-adrenoceptors in peripheral arteries of ovariectomized
      rats.
AB  - We examined whether chronic estrogen replacement has an inhibitory effect on
      stress-induced pressor responses via activation of beta2-adrenoceptor (AR) in
      peripheral arteries of ovariectomized rats. Female Wistar rats aged 9 wk were
      ovariectomized. After 4 wk, pellets containing either 17beta-estradiol (E2) or
      placebo (Pla) were subcutaneously implanted into the rats. After 4 wk of
      treatment, rats underwent cage-switch stress, and, in a separate experiment, a
      subset received an infusion of isoproterenol (ISO) with or without pretreatment
      with the beta1-AR blocker atenolol or the beta2-AR blocker butoxamine. In
      addition, the isolated mesenteric artery was used to assess the concentration
      related relaxing responses to ISO and the beta1- or beta2-AR mRNA level. The cage
      switch stress-induced pressor response was significantly attenuated in the E2
      treated group compared with the Pla-treated group. Pretreatment with atenolol
      reduced blood pressure responses in both groups. However, butoxamine enhanced the
      pressor response only in the E2-treated group, resulting in no difference between
      the two groups. In addition, the intravenous ISO-induced depressor response was
      significantly enhanced in the E2-treated group compared with the Pla-treated
      group. Furthermore, the difference in the depressor response was abolished by
      pretreatment with butoxamine but not by atenolol. In the isolated mesenteric
      artery, butoxamine caused a rightward shift in ISO-induced concentration-related
      relaxation in the E2-treated group. The beta2-AR mRNA level in the mesenteric
      artery was higher in the E2-treated group than in the Pla-treated group. These
      results suggest that estrogen replacement attenuated the stress-induced pressor
      response probably by suppressing vasoconstriction via activation of beta2-ARs in
      peripheral arteries of ovariectomized rats. NEW & NOTEWORTHY In this study, we
      show, for the first time, that estrogen replacement has an inhibitory effect on
      the psychological stress-induced pressor response through vasorelaxation via
      beta2-adrenoceptors, probably due to overexpression of beta2-adrenoceptor mRNA,
      in peripheral arteries of ovariectomized rats.

PMID- 29030335
TI  - Single-cell RNA-seq reveals a distinct transcriptome signature of aneuploid
      hematopoietic cells.
AB  - Cancer cells frequently exhibit chromosomal abnormalities. Specific cytogenetic
      aberrations often are predictors of outcome, especially in hematologic neoplasms,
      such as monosomy 7 in myeloid malignancies. The functional consequences of
      aneuploidy at the cellular level are difficult to assess because of a lack of
      convenient markers to distinguish abnormal from diploid cells. We performed
      single-cell RNA sequencing (scRNA-seq) to study hematopoietic stem and progenitor
      cells from the bone marrow of 4 healthy donors and 5 patients with bone marrow
      failure and chromosome gain or loss. In total, transcriptome sequences were
      obtained from 391 control cells and 588 cells from patients. We characterized
      normal hematopoiesis as binary differentiation from stem cells to erythroid and
      myeloid-lymphoid pathways. Aneuploid cells were distinguished from diploid cells
      in patient samples by computational analyses of read fractions and gene
      expression of individual chromosomes. We confirmed assignment of aneuploidy to
      individual cells quantitatively, by copy-number variation, and qualitatively, by
      loss of heterozygosity. When we projected patients' single cells onto the map of
      normal hematopoiesis, diverse patterns were observed, broadly reflecting clinical
      phenotypes. Patients' monosomy 7 cells showed downregulation of genes involved in
      immune response and DNA damage checkpoint and apoptosis pathways, which may
      contribute to the clonal expansion of monosomy 7 cells with accumulated gene
      mutations. scRNA-seq is a powerful technique through which to infer the
      functional consequences of chromosome gain and loss and explore gene targets for
      directed therapy.

PMID- 29030339
TI  - Muscle alpha-adrenergic responsiveness during exercise and ATP-induced
      vasodilation in chronic obstructive pulmonary disease patients.
AB  - : Sympathetic vasoconstriction is blunted in exercising muscle (functional
      sympatholysis) but becomes attenuated with age. We tested the hypothesis that
      functional sympatholysis is further impaired in chronic obstructive pulmonary
      disease (COPD) patients. We determined leg blood flow and calculated leg vascular
      conductance (LVC) during 1) femoral-arterial Tyramine infusion (evokes endogenous
      norepinephrine release, 1 umol.min-1.kg leg mass-1), 2) one-legged knee extensor
      exercise with and without Tyramine infusion [10 W and 20% of maximal workload
      (WLmax)], 3) ATP (0.05 umol.min-1.kg leg mass-1) and Tyramine infusion, and 4)
      incremental ATP infusions (0.05, 0.3, and 3.0 umol.min-1.kg leg mass-1). We
      included 10 patients with moderate to severe COPD and 8 age-matched healthy
      control subjects. Overall, leg blood flow and LVC were lower in COPD patients
      during exercise ( P < 0.05). Tyramine reduced LVC in both groups at 10-W exercise
      (COPD: -3 +/- 1 ml.min-1.mmHg-1 and controls: -3 +/- 1 ml.min-1.mmHg-1, P < 0.05)
      and 20% WLmax (COPD: -4 +/- 1 ml.min-1.mmHg-1 and controls: -3 +/- 1 ml.min
      1.mmHg-1, P < 0.05) with no difference between groups. Incremental ATP infusions
      induced dose-dependent vasodilation with no difference between groups, and, in
      addition, the vasoconstrictor response to Tyramine infused together with ATP was
      not different between groups (COPD: -0.03 +/- 0.01 l.min-1.kg leg mass-1 vs.
      CONTROLS: -0.04 +/- 0.01 l.min-1.kg leg mass-1, P > 0.05). Compared with age
      matched healthy control subjects, the vasodilatory response to ATP is intact in
      COPD patients and their ability to blunt sympathetic vasoconstriction (functional
      sympatholysis) as evaluated by intra-arterial Tyramine during exercise or ATP
      infusion is maintained. NEW & NOTEWORTHY The ability to blunt sympathetic
      vasoconstriction in exercising muscle and ATP-induced dilation in chronic
      obstructive pulmonary disease patients remains unexplored. Chronic obstructive
      pulmonary disease patients demonstrated similar sympathetic vasoconstriction in
      response to intra-arterial Tyramine during exercise and ATP-induced vasodilation
      compared with age-matched healthy control subjects.

PMID- 29030340
TI  - microRNA-206 correlates with left ventricular function after transcatheter aortic
      valve implantation.
AB  - Transcatheter aortic valve implantation (TAVI) is the method of choice in
      patients with high risk or contraindications for conventional aortic valve
      replacement. However, it is not well understood which parameters predict the
      overall cardiac function postprocedurally. miRNAs are small noncoding RNA
      molecules that repress gene expression by different mechanisms and can also be
      detected in the blood. Recent studies have shown that miRNAs detected in the
      blood may serve as sensitive and specific biomarkers in various diseases;
      therefore, we examined the levels of different microRNAs in the serum of patients
      undergoing TAVI. We thereby intended to find potential predictors for cardiac
      function after TAVI. Serum from patients with aortic valve disease was obtained
      at five different points: before the TAVI procedure, at days 1 and 3 after the
      TAVI procedure, and the day of dischargement and after a period of 3 mo. We next
      performed quantitative real-time PCRs to examine the samples for changes in the
      level of miRNAs previously described as cardiac enriched. Our results show that
      the level of miR-206 in the serum of patients after TAVI correlated negatively
      with the left ventricular ejection fraction of individual patients. We found left
      ventricular function to be better in patients with lower levels of miR-206 after
      implantation of the new valve. A decrease in the serum level of miR-206 may be
      linked to changes in cardiac function of patients after TAVI. Further studies are
      necessary to test the miRNA for its potential value as a prognostic marker. NEW &
      NOTEWORTHY This study is the first to investigate novel miRNA-based biomarkers
      within the context of transcatheter aortic valve implantation. miRNA-206 proved
      to correlate inversely with the postprocedural left ventricular ejection fraction
      of patients.

PMID- 29030341
TI  - Macrophage overexpression of matrix metalloproteinase-9 in aged mice improves
      diastolic physiology and cardiac wound healing after myocardial infarction.
AB  - Matrix metalloproteinase (MMP)-9 increases in the myocardium with advanced age
      and after myocardial infarction (MI). Because young transgenic (TG) mice
      overexpressing human MMP-9 only in macrophages show better outcomes post-MI,
      whereas aged TG mice show a worse aging phenotype, we wanted to evaluate the
      effect of aging superimposed on MI to see if the detrimental effect of aging
      counteracted the benefits of macrophage MMP-9 overexpression. We used 17- to 28
      mo-old male and female C57BL/6J wild-type (WT) and TG mice ( n = 10-21
      mice/group) to evaluate the effects of aging superimposed on MI. Despite similar
      infarct areas and mortality rates at day 7 post-MI, aging TG mice showed improved
      diastolic properties and remodeling index compared with WT mice (both P < 0.05).
      Macrophage numbers were higher in TG than WT mice at days 0 and 7 post-MI, and
      the post-MI increase was due to elevated cluster of differentiation 18 protein
      levels (all P < 0.05). RNA sequencing analysis of cardiac macrophages isolated
      from day 7 post-MI infarcts identified 1,276 statistically different (all P <
      0.05) genes (994 increased and 282 decreased in TG mice). Reduced expression of
      vascular endothelial growth factor A, platelet-derived growth factor subunit A,
      and transforming growth factor-beta3, along with elevated expression of tissue
      inhibitor of MMP-4, in macrophages revealed mechanisms of indirect downstream
      effects on fibroblasts and neovascularization. While collagen accumulation was
      enhanced in TG mice compared with WT mice at days 0 and 7 post-MI ( P < 0.05 for
      both), the post-MI collagen cross-linking ratio was higher in WT mice ( P <
      0.05), consistent with increased diastolic volumes. Vessel numbers [by Griffonia
      ( Bandeiraea) simplicifolia lectin I staining] were decreased in TG mice compared
      with WT mice at days 0 and 7 post-MI ( P < 0.05 for both). In conclusion,
      macrophage-derived MMP-9 improved post-MI cardiac wound healing through direct
      and indirect mechanisms to improve diastolic physiology and remodeling. NEW &
      NOTEWORTHY Aging mice with macrophage overexpression of matrix metalloproteinase
      9 have increased macrophage numbers 7 days after myocardial infarction, resulting
      in improved diastolic physiology and left ventricular remodeling through effects
      on cardiac wound healing.

PMID- 29030342
TI  - Sex-specific impact of aging on the blood pressure response to exercise.
AB  - An exaggerated blood pressure (BP) response to exercise has been linked to
      cardiovascular disease, but little is known about the impact of age and sex on
      this response. Therefore, this study examined the hemodynamic and skeletal muscle
      metabolic response to dynamic plantar flexion exercise, at 40% of maximum plantar
      flexion work rate, in 40 physical activity-matched young (23 +/- 1 yr, n = 20)
      and old (73 +/- 2 yr, n = 20), equally distributed, male and female subjects.
      Central hemodynamics and BP (finometer), popliteal artery blood flow (Doppler
      ultrasound), and skeletal muscle metabolism (31P-magnetic resonance spectroscopy)
      were measured during 5 min of plantar flexion exercise. Popliteal artery blood
      flow and high-energy phosphate responses to exercise were not affected by age or
      sex, whereas aging, independent of sex, attenuated stroke volume and cardiac
      output responses. Systolic BP and mean arterial pressure responses were
      exaggerated in old women (Delta42 +/- 4 and Delta28 +/- 3 mmHg, respectively),
      with all other groups exhibiting similar increases in systolic BP (old men:
      Delta27 +/- 8 mmHg, young men: Delta27 +/- 3 mmHg, and young women: Delta22 +/- 3
      mmHg) and mean arterial pressure (old men: Delta15 +/- 4 mmHg, young men: Delta19
      +/- 2 mmHg, and young women: Delta17 +/- 2 mmHg). Interestingly, the exercise
      induced change in systemic vascular resistance in old women (?0.8 +/- 1.0 mmHg.l
      1.min-1) was augmented compared with young women and young and old men (?-2.8 +/-
      0.5, ?-1.6 +/- 0.6, and ?-3.18 +/- 1.4 mmHg.l-1.min-1, respectively, P < 0.05).
      Thus, in combination, advancing age and female sex results in an exaggerated BP
      response to exercise, likely the result of a failure to reduce systemic vascular
      resistance. NEW & NOTEWORTHY An exaggerated blood pressure response to exercise
      has been linked to cardiovascular disease; however, little is known about how age
      and sex impact this response in healthy individuals. During dynamic exercise,
      older women exhibited an exaggerated blood pressure response driven by an
      inability to lower systemic vascular resistance.

PMID- 29030343
TI  - Carbohydrate restriction with postmeal walking effectively mitigates postprandial
      hyperglycemia and improves endothelial function in type 2 diabetes.
AB  - Postprandial hyperglycemia has deleterious effects on endothelial function.
      Restricting carbohydrate intake and postmeal walking have each been shown to
      reduce postprandial hyperglycemia, but their combination and subsequent effects
      on endothelial function have not been investigated. Here, we sought to examine
      the effect of blunting postprandial hyperglycemia by following a low-carbohydrate
      diet, with or without postmeal walking exercise, on markers of vascular health in
      type 2 diabetes (T2D). In a randomized crossover design, individuals with T2D ( n
      = 11) completed three 4-day controlled diet interventions consisting of 1) low
      carbohydrate diet alone (LC), 2) low-carbohydrate diet with 15-min postmeal walks
      (LC + Ex), and 3) low-fat control diet (CON). Fasting blood samples and brachial
      artery flow-mediated dilation (%FMD) were measured before and after each
      intervention. Total circulating microparticles (MPs), endothelial MPs, platelet
      MPs, monocyte-platelet aggregates, and adhesion molecules were assessed as
      biomarkers of vascular health. There was a significant condition * time
      interaction for %FMD ( P = 0.01), with post hoc tests revealing improved %FMD
      after LC + Ex (+0.8 +/- 1.0%, P = 0.02), with no change after LC or CON.
      Endothelial MPs were significantly reduced with the LC diet by ~45% (from 99 +/-
      60 to 44 +/- 31 MPs/MUl, P = 0.02), with no change after LC + Ex or CON
      (interaction: P = 0.04). Total MPs were lower (main effect time: P = 0.02),
      whereas monocyte-platelet aggregates were higher (main effect time: P < 0.01)
      after all interventions. Plasma adhesion molecules and C-reactive protein were
      unaltered. Attenuating postprandial hyperglycemic excursions using a low
      carbohydrate diet combined with postmeal walking appears to be an effective
      strategy to improve endothelial function in individuals with T2D. NEW &
      NOTEWORTHY Carbohydrate restriction and postmeal walking lower postprandial
      hyperglycemia in individuals with type 2 diabetes. Here, we show that the
      combination significantly improved endothelial function and that carbohydrate
      restriction alone reduced circulating endothelial microparticles in individuals
      with type 2 diabetes. Listen to this article's corresponding podcast at
      http://ajpheart.podbean.com/e/low-carb-diet-and-exercise-improve-endothelial
      health/ .

PMID- 29030344
TI  - Cell Type-Specific Chromatin Signatures Underline Regulatory DNA Elements in
      Human Induced Pluripotent Stem Cells and Somatic Cells.
AB  - RATIONALE: Regulatory DNA elements in the human genome play important roles in
      determining the transcriptional abundance and spatiotemporal gene expression
      during embryonic heart development and somatic cell reprogramming. It is not well
      known how chromatin marks in regulatory DNA elements are modulated to establish
      cell type-specific gene expression in the human heart. OBJECTIVE: We aimed to
      decipher the cell type-specific epigenetic signatures in regulatory DNA elements
      and how they modulate heart-specific gene expression. METHODS AND RESULTS: We
      profiled genome-wide transcriptional activity and a variety of epigenetic marks
      in the regulatory DNA elements using massive RNA-seq (n=12) and ChIP-seq
      (chromatin immunoprecipitation combined with high-throughput sequencing; n=84) in
      human endothelial cells (CD31+CD144+), cardiac progenitor cells (Sca-1+),
      fibroblasts (DDR2+), and their respective induced pluripotent stem cells. We
      uncovered 2 classes of regulatory DNA elements: class I was identified with
      ubiquitous enhancer (H3K4me1) and promoter (H3K4me3) marks in all cell types,
      whereas class II was enriched with H3K4me1 and H3K4me3 in a cell type-specific
      manner. Both class I and class II regulatory elements exhibited stimulatory roles
      in nearby gene expression in a given cell type. However, class I promoters
      displayed more dominant regulatory effects on transcriptional abundance
      regardless of distal enhancers. Transcription factor network analysis indicated
      that human induced pluripotent stem cells and somatic cells from the heart
      selected their preferential regulatory elements to maintain cell type-specific
      gene expression. In addition, we validated the function of these enhancer
      elements in transgenic mouse embryos and human cells and identified a few
      enhancers that could possibly regulate the cardiac-specific gene expression.
      CONCLUSIONS: Given that a large number of genetic variants associated with human
      diseases are located in regulatory DNA elements, our study provides valuable
      resources for deciphering the epigenetic modulation of regulatory DNA elements
      that fine-tune spatiotemporal gene expression in human cardiac development and
      diseases.

PMID- 29030345
TI  - Runx1 Deficiency Protects Against Adverse Cardiac Remodeling After Myocardial
      Infarction.
AB  - BACKGROUND: Myocardial infarction (MI) is a leading cause of heart failure and
      death worldwide. Preservation of contractile function and protection against
      adverse changes in ventricular architecture (cardiac remodeling) are key factors
      to limiting progression of this condition to heart failure. Consequently, new
      therapeutic targets are urgently required to achieve this aim. Expression of the
      Runx1 transcription factor is increased in adult cardiomyocytes after MI;
      however, the functional role of Runx1 in the heart is unknown. METHODS: To
      address this question, we have generated a novel tamoxifen-inducible
      cardiomyocyte-specific Runx1-deficient mouse. Mice were subjected to MI by means
      of coronary artery ligation. Cardiac remodeling and contractile function were
      assessed extensively at the whole-heart, cardiomyocyte, and molecular levels.
      RESULTS: Runx1-deficient mice were protected against adverse cardiac remodeling
      after MI, maintaining ventricular wall thickness and contractile function.
      Furthermore, these mice lacked eccentric hypertrophy, and their cardiomyocytes
      exhibited markedly improved calcium handling. At the mechanistic level, these
      effects were achieved through increased phosphorylation of phospholamban by
      protein kinase A and relief of sarco/endoplasmic reticulum Ca2+-ATPase
      inhibition. Enhanced sarco/endoplasmic reticulum Ca2+-ATPase activity in Runx1
      deficient mice increased sarcoplasmic reticulum calcium content and sarcoplasmic
      reticulum-mediated calcium release, preserving cardiomyocyte contraction after
      MI. CONCLUSIONS: Our data identified Runx1 as a novel therapeutic target with
      translational potential to counteract the effects of adverse cardiac remodeling,
      thereby improving survival and quality of life among patients with MI.

PMID- 29030346
TI  - Diagnostic Accuracy of the Aortic Dissection Detection Risk Score Plus D-Dimer
      for Acute Aortic Syndromes: The ADvISED Prospective Multicenter Study.
AB  - BACKGROUND: Acute aortic syndromes (AASs) are rare and severe cardiovascular
      emergencies with unspecific symptoms. For AASs, both misdiagnosis and overtesting
      are key concerns, and standardized diagnostic strategies may help physicians to
      balance these risks. D-dimer (DD) is highly sensitive for AAS but is inadequate
      as a stand-alone test. Integration of pretest probability assessment with DD
      testing is feasible, but the safety and efficiency of such a diagnostic strategy
      are currently unknown. METHODS: In a multicenter prospective observational study
      involving 6 hospitals in 4 countries from 2014 to 2016, consecutive outpatients
      were eligible if they had >=1 of the following: chest/abdominal/back pain,
      syncope, perfusion deficit, and if AAS was in the differential diagnosis. The
      tool for pretest probability assessment was the aortic dissection detection risk
      score (ADD-RS, 0-3) per current guidelines. DD was considered negative (DD-) if
      <500 ng/mL. Final case adjudication was based on conclusive diagnostic imaging,
      autopsy, surgery, or 14-day follow-up. Outcomes were the failure rate and
      efficiency of a diagnostic strategy for ruling out AAS in patients with ADD
      RS=0/DD- or ADD-RS <=1/DD-. RESULTS: A total of 1850 patients were analyzed. Of
      these, 438 patients (24%) had ADD-RS=0, 1071 patients (58%) had ADD-RS=1, and 341
      patients (18%) had ADD-RS >1. Two hundred forty-one patients (13%) had AAS: 125
      had type A aortic dissection, 53 had type B aortic dissection, 35 had intramural
      aortic hematoma, 18 had aortic rupture, and 10 had penetrating aortic ulcer. A
      positive DD test result had an overall sensitivity of 96.7% (95% confidence
      interval [CI], 93.6-98.6) and a specificity of 64% (95% CI, 61.6-66.4) for the
      diagnosis of AAS; 8 patients with AAS had DD-. In 294 patients with ADD-RS=0/DD-,
      1 case of AAS was observed. This yielded a failure rate of 0.3% (95% CI, 0.1-1.9)
      and an efficiency of 15.9% (95% CI, 14.3-17.6) for the ADD-RS=0/DD- strategy. In
      924 patients with ADD-RS <=1/DD-, 3 cases of AAS were observed. This yielded a
      failure rate of 0.3% (95% CI, 0.1-1) and an efficiency of 49.9% (95% CI, 47.7
      52.2) for the ADD-RS <=1/DD- strategy. CONCLUSIONS: Integration of ADD-RS (either
      ADD-RS=0 or ADD-RS <=1) with DD may be considered to standardize diagnostic rule
      out of AAS. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov.
      Unique identifier: NCT02086136.

PMID- 29030353
TI  - RAD50 Expression Is Associated with Poor Clinical Outcomes after Radiotherapy for
      Resected Non-small Cell Lung Cancer.
AB  - Purpose: Although postoperative radiotherapy is often used to maintain local
      control after surgical resection and chemotherapy for locally advanced non-small
      cell lung cancer (NSCLC), both locoregional failure and distant metastasis remain
      problematic. The mechanisms of therapeutic resistance remain poorly
      understood.Experimental Design: We used reverse-phase protein arrays (RPPA) to
      profile the baseline expression of 170 total and phosphorylated proteins in 70
      NSCLC cell lines to categorize pathways that may contribute to radiation
      resistance. Significant markers identified by RPPA were further analyzed in
      tissue microarrays (TMA) of specimens from 127 patients with NSCLC who had
      received surgery before receiving postoperative radiotherapy. Cox regression
      analysis and log-rank tests were used to identify potential predictive factors.
      We then validated the biological function of the markers in NSCLC cell lines in
      vitroResults: Of the 170 proteins or phospho-proteins profiled, a subset of 12
      proteins was found to correlate with radiation response parameters. TMA analysis
      of the 12 proteins showing the greatest differences in expression in the RPPA
      analysis demonstrated that RAD50 had the strongest correlation with distant
      relapse-free survival, locoregional relapse-free survival, and disease-free
      survival in patients with NSCLC. We confirmed that knockdown of RAD50 sensitized
      NSCLC cells to radiation and that upregulation of RAD50 increased radioresistance
      in in vitro experiments.Conclusions: Upregulated RAD50 may be a predictor of
      radioresistance in patients with lung cancer who received radiotherapy. Clin
      Cancer Res; 24(2); 341-50. (c)2017 AACR.

PMID- 29030347
TI  - Extracellular Matrix Proteomics Reveals Interplay of Aggrecan and Aggrecanases in
      Vascular Remodeling of Stented Coronary Arteries.
AB  - BACKGROUND: Extracellular matrix (ECM) remodeling contributes to in-stent
      restenosis and thrombosis. Despite its important clinical implications, little is
      known about ECM changes post-stent implantation. METHODS: Bare-metal and drug
      eluting stents were implanted in pig coronary arteries with an overstretch under
      optical coherence tomography guidance. Stented segments were harvested 1, 3, 7,
      14, and 28 days post-stenting for proteomics analysis of the media and neointima.
      RESULTS: A total of 151 ECM and ECM-associated proteins were identified by mass
      spectrometry. After stent implantation, proteins involved in regulating
      calcification were upregulated in the neointima of drug-eluting stents. The
      earliest changes in the media were proteins involved in inflammation and
      thrombosis, followed by changes in regulatory ECM proteins. By day 28, basement
      membrane proteins were reduced in drug-eluting stents in comparison with bare
      metal stents. In contrast, the large aggregating proteoglycan aggrecan was
      increased. Aggrecanases of the ADAMTS (a disintegrin and metalloproteinase with
      thrombospondin motifs) family contribute to the catabolism of vascular
      proteoglycans. An increase in ADAMTS-specific aggrecan fragments was accompanied
      by a notable shift from ADAMTS1 and ADAMTS5 to ADAMTS4 gene expression after
      stent implantation. Immunostaining in human stented coronary arteries confirmed
      the presence of aggrecan and aggrecan fragments, in particular, at the contacts
      of the stent struts with the artery. Further investigation of aggrecan presence
      in the human vasculature revealed that aggrecan and aggrecan cleavage were more
      abundant in human arteries than in human veins. In addition, aggrecan synthesis
      was induced on grafting a vein into the arterial circulation, suggesting an
      important role for aggrecan in vascular plasticity. Finally, lack of ADAMTS-5
      activity in mice resulted in an accumulation of aggrecan and a dilation of the
      thoracic aorta, confirming that aggrecanase activity regulates aggrecan abundance
      in the arterial wall and contributes to vascular remodeling. CONCLUSIONS:
      Significant differences were identified by proteomics in the ECM of coronary
      arteries after bare-metal and drug-eluting stent implantation, most notably an
      upregulation of aggrecan, a major ECM component of cartilaginous tissues that
      confers resistance to compression. The accumulation of aggrecan coincided with a
      shift in ADAMTS gene expression. This study provides the first evidence
      implicating aggrecan and aggrecanases in the vascular injury response after
      stenting.

PMID- 29030355
TI  - A Prognostic Bio-Model Based on SQSTM1 and N-Stage Identifies Nasopharyngeal
      Carcinoma Patients at High Risk of Metastasis for Additional Induction
      Chemotherapy.
AB  - Purpose: Metastasis is one of the most important causes of treatment failure in
      nasopharyngeal carcinoma (NPC). In T4 or N2-3 patients at high-risk of
      metastasis, concurrent chemoradiotherapy (CCRT) is inadequate and additional
      induction chemotherapy (IC) is controversial. There is a critical need to develop
      a better patient stratification to efficiently identify patients at high-risk of
      metastasis for additional IC. Recently, Sequestosome 1 (SQSTM1)/p62, an autophagy
      adaptor protein, was identified as one of the metastasis-related proteins in NPC.
      However, the mechanism by which SQSTM1 is involved in NPC metastasis was not
      investigated.Experimental Design: The effect of SQSTM1 on cell migration and
      invasion was examined in vitro and in vivo SQSTM1 expression was analyzed in
      clinical NPC samples using IHC. Luciferase reporter analyses were conducted to
      identify the effects of SQSTM1 on NF-kappaB transcriptional activity. A
      prediction bio-model was constructed by Cox analysis. Retrospective and
      prospective randomized clinical data were adopted to build and test the model,
      respectively.Results: SQSTM1 mediated epithelial to mesenchymal transition (EMT)
      through the NF-kappaB pathway to promote NPC metastasis. Inhibiting SQSTM1
      enhanced sensitivity to cisplatin in NPC cells. In NPC patients, high SQSTM1
      expression was associated with increased risk of distant metastasis. Furthermore,
      we propose a prognostic bio-model based on SQSTM1 and N-stage to predict NPC
      metastasis. Most importantly, our prospective randomized study suggested that IC
      is beneficial for NPC patients with high metastasis risk.Conclusions: The
      prognostic bio-model identifies NPC patients at high-risk of metastasis for
      additional IC. Clin Cancer Res; 24(3); 648-58. (c)2017 AACR.

PMID- 29030354
TI  - Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in
      Patients with Advanced Solid Tumors.
AB  - Purpose: NC-6004, a novel cisplatin nanoparticle developed using micellar
      technology exhibits sustained release of cisplatin and selective distribution to
      tumors. Preclinical data demonstrated a favorable tolerability profile and
      preserved or improved antitumor activity compared with cisplatin across animal
      models. We evaluated the safety and tolerability of NC-6004 and gemcitabine using
      a Bayesian continual reassessment model (N-CRM) to determine the optimal
      dose.Experimental Design: Patients with advanced solid tumors received NC-6004 at
      60 to 180 mg/m2 on day 1 and gemcitabine at 1,250 mg/m2 on days 1 and 8 every 3
      weeks. Dose escalation of NC-6004 began with a single patient run-in until a dose
      limiting toxicity occurred at 180 mg/m2 Cohorts of four patients were enrolled at
      doses predicted by the N-CRM. The maximum tolerated dose (MTD) was defined as
      having the greatest probability of target toxicity <25%. Quality of life was
      assessed using EORTC-QLQ-C30.Results: Among 22 patients, the most common grade
      III/IV hematologic adverse events were leukopenia (68%) and thrombocytopenia
      (59%). Of 20 pretreated patients evaluable for response, half were previously
      exposed to a platinum agent. The MTD was 135 mg/m2 Nine patients were treated at
      the MTD with median treatment duration of 15 weeks (range, 3-50). Tumor shrinkage
      occurred in 11 (55%), partial responses in 3 (15%), and stable disease in 14
      (70%). Most patients reported stable or improved EORTC QLQ-C30
      scores.Conclusions: Greater cisplatin equivalent doses were achieved with no
      clinically significant neuro-, oto-, or nephrotoxicity. These data demonstrate
      tolerability and promising activity of NC-6004 in combination with gemcitabine.
      Clin Cancer Res; 24(1); 43-51. (c)2017 AACR.

PMID- 29030357
TI  - CQC is urged to speed up publication of inspection reports.

PMID- 29030356
TI  - Cell-Cycle and DNA-Damage Response Pathway Is Involved in Leptomeningeal
      Metastasis of Non-Small Cell Lung Cancer.
AB  - Purpose: Leptomeningeal metastasis (LM) is a detrimental complication of non
      small cell lung cancer (NSCLC) and associated with poor prognosis. However, the
      underlying mechanisms of the metastasis process are still poorly
      understood.Experimental Design: We performed next-generation panel sequencing of
      primary tumor tissue, cerebrospinal fluid (CSF), and matched normal controls from
      epidermal growth factor receptor (EGFR) mutation-positive NSCLC patients with
      LM.Results: The status of EGFR-activating mutations was highly concordant between
      primary tumor and CSF. PIK3CA aberrations were high in these patients,
      implicating an association with LM risk. Intriguingly, low overlapping of somatic
      protein-changing variants was observed between paired CSF and primary lesions,
      exhibiting tumor heterogeneity and genetic divergence. Moreover, genes with CSF
      recurrent genomic alterations were predominantly involved in cell-cycle
      regulation and DNA-damage response (DDR), suggesting a role of the pathway in LM
      development.Conclusions: Our study has shed light on the genomic variations of
      NSCLC-LM, demonstrated genetic heterogeneity and divergence, uncovered
      involvement of cell-cycle and DDR pathway, and paved the way for potential
      therapeutic approaches to this unmet medical need. Clin Cancer Res; 24(1); 209
      16. (c)2017 AACR.

PMID- 29030358
TI  - Hunger can be the driving force behind "relapse" of type 2 diabetes.

PMID- 29030359
TI  - CC-chemokine ligand 18 is a useful biomarker associated with disease activity in
      IgG4-related disease.

PMID- 29030360
TI  - Metabolic and cardiovascular benefits of hydroxychloroquine: exploration in a
      wider population at high CV risk.

PMID- 29030362
TI  - NHS staff who refuse flu vaccine this winter will have to give reasons.

PMID- 29030361
TI  - Lack of placental transfer of certolizumab pegol during pregnancy: results from
      CRIB, a prospective, postmarketing, pharmacokinetic study.
AB  - OBJECTIVES: There is a need for effective and safe treatment during pregnancy in
      women with chronic inflammatory diseases. This study evaluated placental transfer
      of certolizumab pegol (CZP), an Fc-free anti-tumour necrosis factor drug, from
      CZP-treated pregnant women to their infants. METHODS: CRIB was a pharmacokinetic
      (PK) study of women >=30 weeks pregnant receiving commercial CZP for a locally
      approved indication (last dose <=35 days prior to delivery). Blood samples were
      collected from mothers, umbilical cords and infants at delivery, and infants
      again at weeks 4 and 8 post-delivery. CZP plasma concentrations were measured
      with a highly sensitive and CZP-specific electrochemiluminescence immunoassay
      (lower limit of quantification 0.032 MUg/mL). RESULTS: Sixteen women entered and
      completed the study. Maternal CZP plasma levels at delivery were within the
      expected therapeutic range (median [range] 24.4 [5.0-49.4] MUg/mL). Of the 16
      infants, 2 were excluded from the per-protocol set: 1 due to missing data at
      birth and 1 due to implausible PK data. Of the remaining 14 infants, 13 had no
      quantifiable CZP levels at birth (<0.032 MUg/mL), and 1 had a minimal CZP level
      of 0.042 MUg/mL (infant/mother plasma ratio 0.0009); no infants had quantifiable
      CZP levels at weeks 4 and 8. Of 16 umbilical cord samples, 1 was excluded due to
      missing data; 3/15 had quantifiable CZP levels (maximum 0.048 MUg/mL).
      CONCLUSIONS: There was no to minimal placental transfer of CZP from mothers to
      infants, suggesting lack of in utero foetal exposure during the third trimester.
      These results support continuation of CZP treatment during pregnancy, when
      considered necessary. TRIAL REGISTRATION NUMBER: NCT02019602; Results.

PMID- 29030363
TI  - Isolated left ventricular non-compaction (LVNC) and recurrent strokes: to
      anticoagulate or not to anticoagulate, that is the question.
AB  - Isolated left ventricular non-compaction (LVNC) is an uncommon primary
      cardiomyopathy associated with significant risk of thromboembolic stroke. We
      report a case of a 69-year-old man with a medical history of ischaemic stroke who
      presented with a stroke for the second time, and during stroke workup
      transthoracic echo was suggestive of increased apical trabeculation. He underwent
      cardiac MRI study to evaluate the left ventricular structure, which revealed LVNC
      cardiomyopathy, which we believe is the main culprit of his recurrent strokes.
      Given the high risk of stroke recurrence, antiplatelets followed by
      anticoagulation for secondary prevention were initiated. This case demonstrates
      the association between LVNC and recurrent stroke, with a literature review
      trying to address the dilemma facing the clinician to decide on anticoagulation
      in such patients.

PMID- 29030364
TI  - So near, yet so far: access to safe abortion services remains elusive for poor
      women in India.
AB  - In this case study, we describe our experiences with a woman employed as a
      housemaid who sought unsafe abortion services from a private doctor. This was her
      sixth pregnancy, after previously giving birth to one son and two daughters and
      undergoing two induced abortions. Her husband remained opposed to the use of
      contraception. Initially, she had sought medical termination of pregnancy through
      a government hospital but was denied because of procedural delays, specifically
      the non-availability of an ultrasonography report consequent to a lack of proof
      of identity (ie, the AADHAAR card, a unique identification card for recording
      biometric and demographic data in India). She finally sought the services of an
      unqualified private physician and received oral abortifacient agents.
      Consequently, she was required to seek treatment for bleeding per vaginum from
      the dispensary staff at a government hospital. We note that many such incidents
      occur in our daily practice but remain unnoticed and undocumented. Although this
      patient was eligible for sterilisation (ie, tubectomy), her husband was
      uncooperative. This case illustrates the lack of decision-making power
      experienced by Indian women who have a low societal status.

PMID- 29030365
TI  - Transient global amnesia following a whole-body cryotherapy session.
AB  - Whole-body cryotherapy (WBC), which consists of a short exposure to very cold and
      dry air in special 'cryo-chambers', is believed to reduce inflammation and
      musculoskeletal pain as well as improve athletes' recovery. This is the case of a
      63-year-old male, who presented with transient global amnesia (TGA) after
      undertaking a WBC session. TGA is a clinical syndrome characterised by a sudden
      onset of anterograde amnesia, sometimes coupled with a retrograde component,
      lasting up to 24 hours without other neurological deficits. Even though the
      patient completely recovered, as expected, in 24 hours, this case highlights that
      WBC is potentially not as risk free as thought to be initially. To conclude,
      before WBC can be medically recommended, well-conducted studies investigating the
      possible adverse events are required.

PMID- 29030366
TI  - Role of transoesophageal echocardiography in renal cell carcinoma: a brief
      review.
AB  - Transoesophageal echocardiography (TOE) is regularly used in cardiac and also
      increasingly in non-cardiac surgeries. It has a leading role in the perioperative
      management of renal cell carcinoma with tumour extension into inferior vena cava.
      We report two cases in which TOE was of immense help for patient management. This
      report highlights the two cases where intraoperative TOE was of immense help to
      establish diagnosis, to modify surgical plan, to guide the surgeon during clamp
      placement, to monitor cardiac function, to rule out tumour embolism and to
      confirm the complete removal of tumour thrombus.

PMID- 29030367
TI  - Patients with common variable immunodeficiency paradoxically have increased rates
      of autoimmune disorders.
AB  - Common variable immunodeficiency (CVID), characterised by disordered B cell
      function, is one of the most common primary immunodeficiency disorders. Patients
      with CVID are at lifelong risk of recurrent infections, particularly of the
      respiratory and gastrointestinal tracts. Paradoxically, given their
      immunocompromised state, patients with CVID are also at significantly increased
      risk of autoimmune disorders, which are seen in almost 25% of cases. The authors
      report a 24-year-old female patient with CVID, manifested as severe
      hypogammaglobulinaemia with recurrent sinopulmonary infections and enterocolitis,
      who presented with transaminitis, chronic diarrhoea and haematemesis. No
      infectious aetiologies were identified. She was diagnosed with coeliac disease
      after a small bowel biopsy and positive response to gluten-free diet.
      Haematemesis was attributed to portal hypertension due to liver cirrhosis, which
      was confirmed via liver biopsy. Coeliac disease can be a cause of diarrhoea in
      patients with immunodeficiency disorders and is often underdiagnosed. It can also
      be the underlying source of liver disease and is an often under-recognised cause
      of cirrhosis. The case presented emphasises the paradoxical and challenging
      relationship that patients with CVID face between immunodeficiency and autoimmune
      disorders, and also highlights that coeliac disease is an under-recognised cause
      of liver disease.

PMID- 29030368
TI  - Iron deficiency anaemia in a coeliac: a cause for concern?
AB  - A 70-year-old woman with a 15-year history of coeliac disease was admitted for
      treatment and investigation of symptomatic anaemia. Of note, she was recently
      commenced on aspirin therapy for retinal artery occlusion. This followed a normal
      gastro-duodenoscopy, colonoscopy and CT abdomen as workup for iron deficiency
      anaemia. On this occasion, the patient was further investigated with small bowel
      capsule endoscopy. This revealed an ulcerated lesion in her proximal jejunum
      suspicious for malignancy, namely lymphoma. A biopsy of the lesion confirmed
      adenomatous changes and high-grade dysplasia without malignant changes. Given the
      endoscopic appearances of the lesion, she was further evaluated with a small
      bowel MRI. This revealed a 3 cm lesion with associated lymphadenopathy but no
      distant metastases. She proceeded to resection of her small bowel which confirmed
      an invasive adenocarcinoma of her proximal jejunum. She is currently undergoing
      adjuvant chemotherapy on an outpatient basis.

PMID- 29030369
TI  - Post laser-assisted in situ keratomileusis keratomycotic malignant glaucoma.
AB  - We report a case of a 24-year-old male patient with post-laser assisted in situ
      keratomileusis (LASIK) culture-proven mycotic keratitis who developed pupillary
      block glaucoma on day 19 of medical management. The case was initially managed
      with multiple Nd-Yag peripheral iridotomy along with systemic and topical
      antiglaucoma medications. However, an emergency therapeutic penetrating
      keratoplasty (TPK) with lens extraction was done in view of persistently raised
      intraocular pressure (IOP) and seclusio pupillae. On postoperative day 1, IOP was
      10 mm Hg with graft clarity 2 plus and deep anterior chamber with no evidence of
      residual infection or recurrence. Pupillary block glaucoma can occur in cases of
      post-LASIK mycotic keratitis, which may necessitate emergency TPK.

PMID- 29030370
TI  - "Golden hello" of L20 000 to be offered to 200 GPs a year, says health secretary.

PMID- 29030373
TI  - Letter by Heinrich-Nols and Kreuzer Regarding Article, "Increased Thromboembolic
      Events With Dabigatran Compared With Vitamin K Antagonism in Left Ventricular
      Assist Device Patients: A Randomized Controlled Pilot Trial".

PMID- 29030371
TI  - Patient and Spousal Health and Outcomes in Heart Failure.
AB  - BACKGROUND: A diagnosis of heart failure (HF) often requires a comprehensive
      lifestyle change to maintain disease stability. When patients with HF are
      married, the spouse frequently assumes the caregiving role. Our objectives were
      to describe the health of spouses of married patients with HF, and examine
      whether the health of a spouse impacts patient outcomes. METHODS AND RESULTS: We
      identified 905 patients that were married at the time of incident HF diagnosis in
      Olmsted County, MN, from 2000 to 2012. Using Rochester Epidemiology Project
      resources, the patient and their spouse's comprehensive longitudinal health
      histories were linked. Spousal health at patient HF diagnosis was assessed by
      comorbidity burden, self-reported difficulty with activities of daily living and
      prior hospitalizations. The associations of spousal health with patient outcomes
      and patient death with spousal outcomes were examined using Cox and Andersen-Gill
      models. Spouses of patients with HF were elderly (mean age, 71 years), often had
      comorbid conditions, and 16% had difficulty with >=1 activities of daily living.
      After adjustment for patient age, sex, and comorbidity, there were no independent
      associations of spousal health and patient risk of death or hospitalization after
      HF diagnosis. However, the risk of hospitalization (adjusted hazard ratio, 1.34;
      95% confidence interval, 1.11-1.60; P=0.002) and death (hazard ratio, 2.10; 95%
      confidence interval, 1.60-2.75; P<0.001) increased in the surviving spouse after
      patient death. CONCLUSIONS: We found no evidence that the health of a spouse
      impacts patient outcomes after HF diagnosis. However, after a patient with HF
      dies, their surviving spouse's risk of hospitalization and death increases.

PMID- 29030374
TI  - Response by Andreas et al to Letter Regarding Article, "Increased Thromboembolic
      Events With Dabigatran Compared With Vitamin K Antagonism in Left Ventricular
      Assist Device Patients: A Randomized Controlled Pilot Trial".

PMID- 29030375
TI  - Primary care improvement in Wales "over reliant" on key individuals.

PMID- 29030372
TI  - Dose-Dependent Effects of the Myosin Activator Omecamtiv Mecarbil on Cross-Bridge
      Behavior and Force Generation in Failing Human Myocardium.
AB  - BACKGROUND: Omecamtiv mecarbil (OM) enhances systolic function in vivo by
      directly binding the myosin cross-bridges (XBs) in the sarcomere. However, the
      mechanistic details governing OM-induced modulation of XB behavior in failing
      human myocardium are unclear. METHODS AND RESULTS: The effects of OM on steady
      state and dynamic XB behavior were measured in chemically skinned myocardial
      preparations isolated from human donor and heart failure (HF) left ventricle. HF
      myocardium exhibited impaired contractile function as evidenced by reduced
      maximal force, magnitude of XB recruitment (Pdf), and a slowed rate of XB
      detachment (krel) at submaximal Ca2+ activations. Ca2+ sensitivity of force
      generation (pCa50) was higher in HF myocardium when compared with donor
      myocardium, both prior to and after OM incubations. OM incubation (0.5 and 1.0
      MUmol/L) enhanced force generation at submaximal Ca2+ activations in a dose
      dependent manner. Notably, OM induced a slowing in krel with 1.0 MUmol/L OM but
      not with 0.5 MUmol/L OM in HF myocardium. Additionally, OM exerted other
      differential effects on XB behavior in HF myocardium as evidenced by a greater
      enhancement in Pdf and slowing in the time course of cooperative XB recruitment
      (Trec), which collectively prolonged achievement of peak force development (Tpk),
      compared with donor myocardium. CONCLUSIONS: Our findings demonstrate that OM
      augments force generation but also prolongs the time course of XB transitions to
      force-bearing states in remodeled HF myocardium, which may extend the systolic
      ejection time in vivo. Optimal OM dosing is critical for eliciting enhanced
      systolic function without excessive prolongation of systolic ejection time, which
      may compromise diastolic filling.

PMID- 29030376
TI  - Disfiguring facial pyoderma vegetans with an excellent outcome.
AB  - We describe a case of disfiguring facial pyoderma vegetans in order to highlight
      the challenges in managing this rare skin condition and review the literature.A
      54-year-old woman presented to dermatology clinic with a 3-month history of a
      left-sided facial lesion, which had been treated as an infected sebaceous cyst.
      The lesion had dramatically increased in size in the weeks prior to presentation.
      There was a history of Crohn's disease and ileal adenocarcinoma, both of which
      were in remission. A clinical diagnosis of pyoderma vegetans was made and the
      patient responded well to immunosuppressive therapy with oral ciclosporin. Carbon
      dioxide (CO2) laser resurfacing to residual scarring contributed to an excellent
      cosmetic result.

PMID- 29030377
TI  - Spontaneous closure of ventricular septal perforation following percutaneous
      coronary intervention for acute myocardial infarction.
AB  - We report on an 84-year-old woman with anteroseptal acute myocardial infarction.
      Emergency coronary angiography revealed the occlusion of proximal left anterior
      descending artery without collateral circulation, and percutaneous coronary
      intervention was performed. Two drug eluting stents were implanted, and the
      procedure was concluded with thrombolysis in myocardial infarction grade 3
      without complications. Postoperatively, no murmur was audible on auscultation and
      no shunt flow was observed on transthoracic echocardiography (TTE), and normal
      blood pressure was maintained. On day 2, however, the patient's vital signs
      deteriorated to a state of shock and systolic murmur appeared at the apical
      region. TTE showed a left-to-right shunt in the apical septal region, and
      ventricular septal perforation was diagnosed. Although emergency surgery was
      considered, the patient's vital signs improved the following day. The
      disappearance of the cardiac murmur and the shunt was confirmed. The clinical
      course was uneventful thereafter, and the patient was discharged.

PMID- 29030378
TI  - Worsening Guillain-Barre syndrome: harbinger of IRIS in HIV?
AB  - We report an HIV patient aged 38 years with acute inflammatory demyelinating
      polyradiculoneuropathy subtype of Guillain-Barre syndrome (GBS) as the only
      manifestation of seroconversion and worsening of GBS being the harbinger of
      immune reconstitution inflammatory syndrome (IRIS). To date, only 5 cases of GBS
      during IRIS are reported. They manifested either during the third week or later
      after starting highly active antiretroviral therapy (HAART). Our patient
      witnessed worsening weakness by fifth day after starting HAART, even before the
      occurrence of Pneumocystis jirovecii pneumonia, cautioning one of the impending
      serious complications of IRIS and helped us initiate steroids at an early date.

PMID- 29030379
TI  - Right Ventricular Pacing Increases Risk of Appropriate Implantable Cardioverter
      Defibrillator Shocks Asymmetrically: An Analysis of the ALTITUDE Database.
AB  - BACKGROUND: Right ventricular pacing (RVP) increases risk of atrial fibrillation
      in patients with implantable cardioverter-defibrillators (ICDs), but ventricular
      proarrhythmia is less clear. We analyzed a large remote monitoring database to
      assess this question. METHODS AND RESULTS: Patients with single- or dual-chamber
      ICDs, engaged in remote monitoring for at least 6 months and with unchanged
      tachycardia programming, were included. %RVP was derived for each weekly
      transmission. ICD electrograms preceding the first shock were adjudicated. Among
      425 625 transmissions received from 8435 patients, 389 appropriate shocks
      occurred over a mean follow-up of 15.0+/-8.8 months. In a time-dependent Cox
      proportional hazards model, transmissions with 80% to 98% RVP were associated
      with a hazard ratio of 1.56 for an appropriate shock in the subsequent week
      compared with <1% RVP (95% CI, 1.01-2.41; P=0.04). By contrast, >=98% RVP trended
      toward a lower risk of an appropriate shock (hazard ratio, 0.61; 95% CI, 0.33
      1.12; P=0.108). Lifetime cumulative %RVP was closely correlated with weekly %RVP
      (R2=0.907) and was similarly associated with increased risk of appropriate shocks
      at 80% to 98% RVP (hazard ratio, 1.57; 95% CI, 1.01-2.44; P=0.046) but not at
      >=98% RVP (hazard ratio, 0.49; 95% CI, 0.24-1.01; P=0.052). These results were
      driven by dual-chamber devices, but unaffected by PVC counts or programming. Male
      sex and age were also associated with appropriate ICD shocks. CONCLUSIONS:
      Increasing frequency of RVP is associated with a progressively increased risk of
      appropriate ICD shocks until >=98% RVP. RVP may have ventricular proarrhythmia
      because of competition of paced and intrinsic rhythm in ICD patients.

PMID- 29030381
TI  - Risk Stratification for Sudden Cardiac Death in Individuals Without Structural
      Disease: Implications From Studies of Rare Genetic Arrhythmic Disorders.

PMID- 29030382
TI  - Right Ventricular Pacing: Can More of a Bad Thing Be Good?

PMID- 29030380
TI  - Association Between QT-Interval Components and Sudden Cardiac Death: The ARIC
      Study (Atherosclerosis Risk in Communities).
AB  - BACKGROUND: Several reports have demonstrated that prolongation of the QT
      interval is associated with sudden cardiac death (SCD). However, it is unknown
      whether any of the components within the QT interval are responsible for its
      association with SCD. METHODS AND RESULTS: We examined the association of the
      individual QT-interval components (R-wave onset to R-peak, R-peak to R-wave end,
      ST-segment, T-wave onset to T-peak, and T-peak to T-wave end) with SCD in 12 241
      participants (54+/-5.7 years; 26% black; 55% women) from the ARIC study
      (Atherosclerosis Risk in Communities). The QT interval and its components were
      measured at baseline (1987-1989) from 12-lead ECGs. SCD cases were adjudicated by
      a group of physicians through December 31, 2012. During a median follow-up of
      23.6 years, a total of 346 cases of SCD were identified. Although prolongation of
      the QT interval was associated with a 49% increased risk of SCD (hazard ratio,
      1.49; 95% confidence interval, 1.01-2.18), only the T-wave onset to T-peak
      component (per 1-SD increase: hazard ratio, 1.19; 95% confidence interval, 1.06
      1.34) was associated with SCD and not any of the other components in separate
      models. When all of the QT-interval components were included in the same model, T
      wave onset to T-peak remained the strongest predictor of SCD (per 1-SD increase:
      hazard ratio, 1.21; 95% confidence interval, 1.06-1.37). CONCLUSIONS: The risk of
      SCD with the QT interval is driven by prolongation of the T-wave onset to T-peak
      component. This suggests that shifting the focus from the overall QT interval to
      its individual components will refine SCD prediction in the community.

PMID- 29030385
TI  - Long-term follow-up after bilateral percutaneous epiphysiodesis around the knee
      to reduce excessive predicted final height.
AB  - CONTEXT: Percutaneous epiphysiodesis (PE) around the knee to reduce predicted
      excessive final height. Studies until now included small numbers of patients and
      short follow-up periods. OBJECTIVE AND DESIGN: This Dutch multicentre, long-term,
      retrospective, follow-up study aimed to assess adult height (AH), complications,
      knee function and patient satisfaction after PE. The primary hypothesis was that
      PE around the knee in constitutionally tall boys and girls is an effective
      treatment for reducing final height with low complication rates and a high level
      of patient satisfaction. PARTICIPANTS: 77 treated adolescents and 60 comparisons.
      INTERVENTION: Percutaneous epiphysiodesis. OUTCOME: AH, complications, knee
      function, satisfaction. RESULTS: In the PE-treated group, final height was 7.0 cm
      (+/-6.3 cm) lower than predicted in boys and 5.9 cm (+/-3.7 cm) lower than
      predicted in girls. Short-term complications in file search were seen in 5.1%
      (three infections, one temporary nerve injury), one requiring reoperation. Long
      term complications in file search were seen in 2.6% (axis deformity 1.3%,
      prominent head of fibula 1.3%). No significant difference in knee function was
      found between treated cases and comparisons. Satisfaction was high in both the
      comparison and PE groups; most patients in the PE group recommended PE as the
      treatment for close relatives with tall stature. CONCLUSION: PE is safe and
      effective in children with predicted excessive AH. There was no difference in
      patient satisfaction between the PE and comparison group. Careful and detailed
      counselling is needed before embarking on treatment.

PMID- 29030383
TI  - Twelve-Week 24/7 Ambulatory Artificial Pancreas With Weekly Adaptation of Insulin
      Delivery Settings: Effect on Hemoglobin A1c and Hypoglycemia.
AB  - OBJECTIVE: Artificial pancreas (AP) systems are best positioned for optimal
      treatment of type 1 diabetes (T1D) and are currently being tested in outpatient
      clinical trials. Our consortium developed and tested a novel adaptive AP in an
      outpatient, single-arm, uncontrolled multicenter clinical trial lasting 12 weeks.
      RESEARCH DESIGN AND METHODS: Thirty adults with T1D completed a continuous
      glucose monitor (CGM)-augmented 1-week sensor-augmented pump (SAP) period. After
      the AP was started, basal insulin delivery settings used by the AP for
      initialization were adapted weekly, and carbohydrate ratios were adapted every 4
      weeks by an algorithm running on a cloud-based server, with automatic data upload
      from devices. Adaptations were reviewed by expert study clinicians and patients.
      The primary end point was change in hemoglobin A1c (HbA1c). Outcomes are reported
      adhering to consensus recommendations on reporting of AP trials. RESULTS: Twenty
      nine patients completed the trial. HbA1c, 7.0 +/- 0.8% at the start of AP use,
      improved to 6.7 +/- 0.6% after 12 weeks (-0.3, 95% CI -0.5 to -0.2, P < 0.001).
      Compared with the SAP run-in, CGM time spent in the hypoglycemic range improved
      during the day from 5.0 to 1.9% (-3.1, 95% CI -4.1 to -2.1, P < 0.001) and
      overnight from 4.1 to 1.1% (-3.1, 95% CI -4.2 to -1.9, P < 0.001). Whereas
      carbohydrate ratios were adapted to a larger extent initially with minimal
      changes thereafter, basal insulin was adapted throughout. Approximately 10% of
      adaptation recommendations were manually overridden. There were no protocol
      related serious adverse events. CONCLUSIONS: Use of our novel adaptive AP yielded
      significant reductions in HbA1c and hypoglycemia.

PMID- 29030387
TI  - Discharge communication: do parents hear what we say?

PMID- 29030386
TI  - Physiological stability in an indigenous sleep device: a randomised controlled
      trial.
AB  - OBJECTIVE: To compare overnight oxygen saturation, heart rate and the thermal
      environment of infants sleeping in an indigenous sleep device (wahakura) or
      bassinet to identify potential risks and benefits. DESIGN: Randomised controlled
      trial. SETTING: Family homes in low socio-economic areas in New Zealand.
      PATIENTS: 200 mainly Maori mothers and their infants. INTERVENTIONS: Participants
      received a wahakura or bassinet from birth. MAIN OUTCOME MEASURES: Overnight
      oximetry, heart rate and temperature at 1 month. RESULTS: Intention-to-treat
      analysis for 83 bassinet and 84 wahakura infants showed no significant
      differences between groups for the mean time oxygen saturation (SpO2) was less
      than 94% (0.54 min, 95% CI -1.36 to 2.45) or less than 90% (0.22 min, 95% CI 
      0.56 to 1.00), the mean number of SpO2 dips per hour >5% (-0.19, 95% CI -3.07 to
      2.69) or >10% (-0.41, 95% CI -1.63 to 0.81), mean heart rate (1.99 beats/min, 95%
      CI -1.02 to 4.99), or time shin temperature >36 degrees C (risk ratio (RR): 0.63,
      95% CI 0.13 to 2.99) or <34 degrees C (RR: 0.89, 95% CI 0.61 to 1.30). A per
      protocol analysis of 45 bassinet and 26 wahakura infants and an as-used analysis
      of 104 infants in a bassinet and 48 in a wahakura found no significant
      differences between groups for all outcome measures. CONCLUSIONS: This indigenous
      sleep device is at least as safe as the currently recommended bassinet, which
      supports its use as a sleep environment that offers an alternative way of bed
      sharing. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials
      Registry: ACTRN12610000993099.

PMID- 29030384
TI  - Follow-up brain imaging of 37 children with congenital Zika syndrome: case series
      study.
AB  - Objective To compare initial brain computed tomography (CT) scans with follow-up
      CT scans at one year in children with congenital Zika syndrome, focusing on
      cerebral calcifications.Design Case series study.Setting Barao de Lucena
      Hospital, Pernambuco state, Brazil.Participants 37 children with probable or
      confirmed congenital Zika syndrome during the microcephaly outbreak in 2015 who
      underwent brain CT shortly after birth and at one year follow-up.Main outcome
      measure Differences in cerebral calcification patterns between initial and follow
      up scans.Results 37 children were evaluated. All presented cerebral
      calcifications on the initial scan, predominantly at cortical-white matter
      junction. At follow-up the calcifications had diminished in number, size, or
      density, or a combination in 34 of the children (92%, 95% confidence interval 79%
      to 97%), were no longer visible in one child, and remained unchanged in two
      children. No child showed an increase in calcifications. The calcifications at
      the cortical-white matter junction which were no longer visible at follow-up
      occurred predominately in the parietal and occipital lobes. These imaging changes
      were not associated with any clear clinical improvements.Conclusion The detection
      of cerebral calcifications should not be considered a major criterion for late
      diagnosis of congenital Zika syndrome, nor should the absence of calcifications
      be used to exclude the diagnosis.

PMID- 29030388
TI  - Are prevalence measures better than incidence measures in sports injury research?

PMID- 29030389
TI  - High precompetition injury rate dominates the injury profile at the Rio 2016
      Summer Paralympic Games: a prospective cohort study of 51 198 athlete days.
AB  - OBJECTIVES: To describe the incidence of injury in the precompetition and
      competition periods of the Rio 2016 Summer Paralympic Games. METHODS: A total of
      3657 athletes from 78 countries, representing 83.4% of all athletes at the Games,
      were monitored on the web-based injury and illness surveillance system over 51
      198 athlete days during the Rio 2016 Summer Paralympic Games. Injury data were
      obtained daily from teams with their own medical support. RESULTS: A total of 510
      injuries were reported during the 14-day Games period, with an injury incidence
      rate (IR) of 10.0 injuries per 1000 athlete days (12.1% of all athletes
      surveyed). The highest IRs were reported for football 5-a-side (22.5), judo
      (15.5) and football 7-a-side (15.3) compared with other sports (p<0.05).
      Precompetition injuries were significantly higher than in the competition period
      (risk ratio: 1.40, p<0.05), and acute traumatic injuries were the most common
      injuries at the Games (IR of 5.5). The shoulder was the most common anatomical
      area affected by injury (IR of 1.8). CONCLUSION: The data from this study
      indicate that (1) IRs were lower than those reported for the London 2012 Summer
      Paralympic Games, (2) the sports of football 5-a-side, judo and football 7-a-side
      were independent risk factors for injury, (3) precompetition injuries had a
      higher IR than competition period injuries, (4) injuries to the shoulder were the
      most common. These results would allow for comparative data to be collected at
      future editions of the Games and can be used to inform injury prevention
      programmes.

PMID- 29030390
TI  - APC/CFZR-1 Controls SAS-5 Levels To Regulate Centrosome Duplication in
      Caenorhabditis elegans.
AB  - As the primary microtubule-organizing center, centrosomes play a key role in
      establishing mitotic bipolar spindles that secure correct transmission of genomic
      content. For the fidelity of cell division, centrosome number must be strictly
      controlled by duplicating only once per cell cycle. Proper levels of centrosome
      proteins are shown to be critical for normal centrosome number and function.
      Overexpressing core centrosome factors leads to extra centrosomes, while
      depleting these factors results in centrosome duplication failure. In this
      regard, protein turnover by the ubiquitin-proteasome system provides a vital
      mechanism for the regulation of centrosome protein levels. Here, we report that
      FZR-1, the Caenorhabditis elegans homolog of Cdh1/Hct1/Fzr, a coactivator of the
      anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase, functions
      as a negative regulator of centrosome duplication in the C. elegans embryo.
      During mitotic cell division in the early embryo, FZR-1 is associated with
      centrosomes and enriched at nuclei. Loss of fzr-1 function restores centrosome
      duplication and embryonic viability to the hypomorphic zyg-1(it25) mutant, in
      part, through elevated levels of SAS-5 at centrosomes. Our data suggest that the
      APC/CFZR-1 regulates SAS-5 levels by directly recognizing the conserved KEN-box
      motif, contributing to proper centrosome duplication. Together, our work shows
      that FZR-1 plays a conserved role in regulating centrosome duplication in C.
      elegans.

PMID- 29030391
TI  - The effect of plasma auto-IgGs on CD4+ T cell apoptosis and recovery in HIV
      infected patients under antiretroviral therapy.
AB  - Although effective antiretroviral therapy (ART) suppresses HIV viral replication,
      prevents AIDS-related complications, and prolongs life, a proportion of patients
      fails to restore the patients' CD4+ T cell number to the level of healthy
      individuals. Increased mortality and morbidity have been observed in these
      patients. In the current study, we have investigated the role of auto-IgGs in
      CD4+ T cell apoptosis and recovery in a cross-sectional study. All HIV+ subjects
      were on viral-suppressive ART treatment with a different degree of CD4+ T cell
      reconstitution. Total auto-IgG binding on CD4+ T cell surfaces and its associated
      apoptosis and CD4+ T cell recovery were analyzed by flow cytometry ex vivo. Total
      IgGs from plasma were tested for their binding capacities to CD4+ T cell surfaces
      and their mediation to CD4+ T cell death through NK cell cytotoxicity in vitro.
      HIV+ subjects had increased surface binding of auto-IgGs on CD4+ T cells compared
      with healthy controls, and IgG binding was associated with elevated CD4+ T cell
      apoptosis in HIV+ subjects but not in healthy controls. Plasma IgGs from HIV+
      subjects bound to CD4+ T cells and induced cell apoptosis through NK cytotoxicity
      in vitro. Soluble CD4 (sCD4) preincubation prevented NK cell-mediated CD4+ T cell
      death. Our results suggest that plasma autoantibodies may play a role in some
      HIV+ patients with poor CD4+ T cell recovery under viral-suppressive ART.

PMID- 29030392
TI  - Hydrogen Sulfide Preserves Endothelial Nitric Oxide Synthase Function by
      Inhibiting Proline-Rich Kinase 2: Implications for Cardiomyocyte Survival and
      Cardioprotection.
AB  - Hydrogen sulfide (H2S) exhibits beneficial effects in the cardiovascular system,
      many of which depend on nitric oxide (NO). Proline-rich tyrosine kinase 2 (PYK2),
      a redox-sensitive tyrosine kinase, directly phosphorylates and inhibits
      endothelial NO synthase (eNOS). We investigated the ability of H2S to relieve
      PYK2-mediated eNOS inhibition and evaluated the importance of the H2S/PYK2/eNOS
      axis on cardiomyocyte injury in vitro and in vivo. Exposure of H9c2
      cardiomyocytes to H2O2 or pharmacologic inhibition of H2S production increased
      PYK2 (Y402) and eNOS (Y656) phosphorylation. These effects were blocked by
      treatment with Na2S or by overexpression of cystathionine gamma-lyase (CSE). In
      addition, PYK2 overexpression reduced eNOS activity in a H2S-reversible manner.
      The viability of cardiomyocytes exposed to Eta2Omicron2 was reduced and declined
      further after the inhibition of H2S production. PYK2 downregulation, l-cysteine
      supplementation, or CSE overexpression alleviated the effects of H2O2 on H9c2
      cardiomyocyte survival. Moreover, H2S promoted PYK2 sulfhydration and inhibited
      its activity. In vivo, H2S administration reduced reactive oxygen species levels,
      as well as PYK2 (Y402) and eNOS (Y656) phosphorylation. Pharmacologic blockade of
      PYK2 or inhibition of PYK2 activation by Na2S reduced myocardial infarct size in
      mice. Coadministration of a PYK2 inhibitor and Na2S did not result in additive
      effects on infarct size. We conclude that H2S relieves the inhibitory effect of
      PYK2 on eNOS, allowing the latter to produce greater amounts of NO, thereby
      affording cardioprotection. Our results unravel the existence of a novel H2S-NO
      interaction and identify PYK2 as a crucial target for the protective effects of
      H2S under conditions of oxidative stress.

PMID- 29030395
TI  - Dignitarian medical ethics.
AB  - Philosophers and bioethicists are typically sceptical about invocations of
      dignity in ethical debates. Many believe that dignity is essentially devoid of
      meaning: either a mere rhetorical gesture used in the absence of good argument or
      a faddish term for existing values like autonomy and respect. On the other hand,
      the patient experience of dignity is a substantial area of research in healthcare
      fields like nursing and palliative care. In this paper, it is argued that
      philosophers have much to learn from the concrete patient experiences described
      in healthcare literature. Dignity is conferred on people when they are treated as
      having equal status, something the sick and frail are often denied in healthcare
      settings. The importance of equal status as a unique value has been forcefully
      argued and widely recognised in political philosophy in the last 15 years. This
      paper brings medical ethics up to date with philosophical discussion about the
      value of equal status by developing an equal status conception of dignity.

PMID- 29030393
TI  - Fanconi anemia FANCD2 and FANCI proteins regulate the nuclear dynamics of
      splicing factors.
AB  - Proteins disabled in the cancer-prone disorder Fanconi anemia (FA) ensure the
      maintenance of chromosomal stability during DNA replication. FA proteins regulate
      replication dynamics, coordinate replication-coupled repair of interstrand DNA
      cross-links, and mitigate conflicts between replication and transcription. Here
      we show that FANCI and FANCD2 associate with splicing factor 3B1 (SF3B1), a key
      spliceosomal protein of the U2 small nuclear ribonucleoprotein (U2 snRNP). FANCI
      is in close proximity to SF3B1 in the nucleoplasm of interphase and mitotic
      cells. Furthermore, we find that DNA replication stress induces the release of
      SF3B1 from nuclear speckles in a manner that depends on FANCI and on the activity
      of the checkpoint kinase ATR. In chromatin, both FANCD2 and FANCI associate with
      SF3B1, prevent accumulation of postcatalytic intron lariats, and contribute to
      the timely eviction of splicing factors. We propose that FANCD2 and FANCI
      contribute to the organization of functional domains in chromatin, ensuring the
      coordination of DNA replication and cotranscriptional processes.

PMID- 29030396
TI  - Faecal microbiota transplantation donor stools need screening for poliovirus.

PMID- 29030397
TI  - Poor health as a potential risk factor for job loss due to automation: the case
      of Norway.
AB  - OBJECTIVE: This study aimed to quantify the extent to which health
      characteristics of workers are related to the potential risk of experiencing job
      displacement due to automation. METHODS: Linking the 2015 Norwegian Statistics on
      Income and Living Conditions survey (n=6393) with predicted probabilities of
      automation by occupation, we used Kruskal-Wallis tests and multivariate
      generalised linear models to assess the association between long-standing
      illnesses and risk of job automation. RESULTS: Individuals with long-standing
      illnesses face substantially greater risks of losing their job due to automation.
      Whereas the average risk of job automation is 57% for men and 49% for women with
      long-standing illnesses, the risk is only 50% for men and 44% for women with
      limitations (p<0.001). Controlling for age, having a long-standing illness
      significantly increases the relative risk of facing job automation among men
      (risk ratio (RR) 1.13, 95% CI 1.09 to 1.19), as well as women (RR 1.11, 95% CI
      1.05 to 1.17). While, among men, the association between long-standing illness
      and risk of job automation remains significant when controlling for education and
      income, it becomes insignificant among women. CONCLUSIONS: Individuals with poor
      health are likely to carry the highest burden of technological change in terms of
      worsening employment prospects because of working in occupations
      disproportionally more likely to be automated. Although the extent of technology
      related job displacement will depend on several factors, given the far-reaching
      negative consequences of job loss on health and well-being, this process
      represents a significant challenge for public health and social equity.

PMID- 29030394
TI  - PtdIns3P controls mTORC1 signaling through lysosomal positioning.
AB  - The mechanistic target of rapamycin complex 1 (mTORC1) is a protein kinase
      complex that localizes to lysosomes to up-regulate anabolic processes and down
      regulate autophagy. Although mTORC1 is known to be activated by lysosome
      positioning and by amino acid-stimulated production of phosphatidylinositol 3
      phosphate (PtdIns3P) by the lipid kinase VPS34/PIK3C3, the mechanisms have been
      elusive. Here we present results that connect these seemingly unrelated pathways
      for mTORC1 activation. Amino acids stimulate recruitment of the PtdIns3P-binding
      protein FYCO1 to lysosomes and promote contacts between FYCO1 lysosomes and
      endoplasmic reticulum that contain the PtdIns3P effector Protrudin. Upon
      overexpression of Protrudin and FYCO1, mTORC1-positive lysosomes translocate to
      the cell periphery, thereby facilitating mTORC1 activation. This requires the
      ability of Protrudin to bind PtdIns3P. Conversely, upon VPS34 inhibition, or
      depletion of Protrudin or FYCO1, mTORC1-positive lysosomes cluster perinuclearly,
      accompanied by reduced mTORC1 activity under nutrient-rich conditions.
      Consequently, the transcription factor EB enters the nucleus, and autophagy is up
      regulated. We conclude that PtdIns3P-dependent lysosome translocation to the cell
      periphery promotes mTORC1 activation.

PMID- 29030398
TI  - On the effect of hyperaldosteronism-inducing mutations in Na/K pumps.
AB  - Primary aldosteronism, a condition in which too much aldosterone is produced and
      that leads to hypertension, is often initiated by an aldosterone-producing
      adenoma within the zona glomerulosa of the adrenal cortex. Somatic mutations of
      ATP1A1, encoding the Na/K pump alpha1 subunit, have been found in these adenomas.
      It has been proposed that a passive inward current transported by several of
      these mutant pumps is a "gain-of-function" activity that produces membrane
      depolarization and concomitant increases in aldosterone production. Here, we
      investigate whether the inward current through mutant Na/K pumps is large enough
      to induce depolarization of the cells that harbor them. We first investigate
      inward currents induced by these mutations in Xenopus Na/K pumps expressed in
      Xenopus oocytes and find that these inward currents are similar in amplitude to
      wild-type outward Na/K pump currents. Subsequently, we perform a detailed
      functional evaluation of the human Na/K pump mutants L104R, delF100-L104, V332G,
      and EETA963S expressed in Xenopus oocytes. By combining two-electrode voltage
      clamp with [3H]ouabain binding, we measure the turnover rate of these inward
      currents and compare it to the turnover rate for outward current through wild
      type pumps. We find that the turnover rate of the inward current through two of
      these mutants (EETA963S and L104R) is too small to induce significant cell
      depolarization. Electrophysiological characterization of another
      hyperaldosteronism-inducing mutation, G99R, reveals the absence of inward
      currents under many different conditions, including in the presence of the
      regulator FXYD1 as well as with mammalian ionic concentrations and body
      temperatures. Instead, we observe robust outward currents, but with significantly
      reduced affinities for intracellular Na+ and extracellular K+ Collectively, our
      results point to loss-of-function as the common mechanism for the
      hyperaldosteronism induced by these Na/K pump mutants.

PMID- 29030399
TI  - Robust lysosomal calcium signaling through channel TRPML1 is impaired by
      lysosomal lipid accumulation.
AB  - The transient receptor potential cation channel mucolipin 1 (TRPML1) channel is a
      conduit for lysosomal calcium efflux, and channel activity may be affected by
      lysosomal contents. The lysosomes of retinal pigmented epithelial (RPE) cells are
      particularly susceptible to build-up of lysosomal waste products because they
      must degrade the outer segments phagocytosed daily from adjacent photoreceptors;
      incomplete degradation leads to accumulation of lipid waste in lysosomes. This
      study asks whether stimulation of TRPML1 can release lysosomal calcium in RPE
      cells and whether such release is affected by lysosomal accumulations. The TRPML
      agonist ML-SA1 raised cytoplasmic calcium levels in mouse RPE cells, hesRPE
      cells, and ARPE-19 cells; this increase was rapid, robust, reversible, and
      reproducible. The increase was not altered by extracellular calcium removal or by
      thapsigargin but was eliminated by lysosomal rupture with glycyl-l-phenylalanine
      beta-naphthylamide. Treatment with desipramine to inhibit acid sphingomyelinase
      or YM201636 to inhibit PIKfyve also reduced the cytoplasmic calcium increase
      triggered by ML-SA1, whereas RPE cells from TRPML1-/- mice showed no response to
      ML-SA1. Cotreatment with chloroquine and U18666A induced formation of neutral,
      autofluorescent lipid in RPE lysosomes and decreased lysosomal Ca2+ release.
      Lysosomal Ca2+ release was also impaired in RPE cells from the ATP-binding
      cassette, subfamily A, member 4-/- mouse model of Stargardt's retinal dystrophy.
      Neither TRPML1 mRNA nor total lysosomal calcium levels were altered in these
      models, suggesting a more direct effect on the channel. In summary, stimulation
      of TRPML1 elevates cytoplasmic calcium levels in RPE cells, but this response is
      reduced by lysosomal accumulation.-Gomez, N. M., Lu, W. Lim, J. C., Kiselyov, K.,
      Campagno, K. E., Grishchuk, Y., Slaugenhaupt, S. A., Pfeffer, B., Fliesler, S.
      J., Mitchell, C. H. Robust lysosomal calcium signaling through channel TRPML1 is
      impaired by lysosomal lipid accumulation.

PMID- 29030400
TI  - MicroRNA Signature of Cigarette Smoking and Evidence for a Putative Causal Role
      of MicroRNAs in Smoking-Related Inflammation and Target Organ Damage.
AB  - BACKGROUND: Cigarette smoking increases risk for multiple diseases. MicroRNAs
      regulate gene expression and may play a role in smoking-induced target organ
      damage. We sought to describe a microRNA signature of cigarette smoking and
      relate it to smoking-associated clinical phenotypes, gene expression, and lung
      inflammatory signaling. METHODS AND RESULTS: Expression profiling of 283
      microRNAs was conducted on whole blood-derived RNA from 5023 Framingham Heart
      Study participants (54.0% women; mean age, 55+/-13 years) using TaqMan assays and
      high-throughput reverse transcription quantitative polymerase chain reaction.
      Associations of microRNA expression with smoking status and associations of
      smoking-related microRNAs with inflammatory biomarkers and pulmonary function
      were tested with linear mixed effects models. We identified a 6-microRNA
      signature of smoking. Five of the 6 smoking-related microRNAs were associated
      with serum levels of C-reactive protein or interleukin-6; miR-1180 was associated
      with pulmonary function measures at a marginally significant level. Bioinformatic
      evaluation of smoking-associated genes coexpressed with the microRNA signature of
      cigarette smoking revealed enrichment for immune-related pathways. Smoking
      associated microRNAs altered expression of selected inflammatory mediators in
      cell culture gain-of-function assays. CONCLUSIONS: We characterized a novel
      microRNA signature of cigarette smoking. The top microRNAs were associated with
      systemic inflammatory markers and reduced pulmonary function, correlated with
      expression of genes involved in immune function, and were sufficient to modulate
      inflammatory signaling. Our results highlight smoking-associated microRNAs and
      are consistent with the hypothesis that smoking-associated microRNAs serve as
      mediators of smoking-induced inflammation and target organ damage. These findings
      call for further mechanistic studies to explore the diagnostic and therapeutic
      use of smoking-related microRNAs.

PMID- 29030401
TI  - A Comparison of Whole Genome Sequencing to Multigene Panel Testing in
      Hypertrophic Cardiomyopathy Patients.
AB  - BACKGROUND: As DNA sequencing costs decline, genetic testing options have
      expanded. Whole exome sequencing and whole genome sequencing (WGS) are entering
      clinical use, posing questions about their incremental value compared with
      disease-specific multigene panels that have been the cornerstone of genetic
      testing. METHODS AND RESULTS: Forty-one patients with hypertrophic cardiomyopathy
      who had undergone targeted hypertrophic cardiomyopathy genetic testing (either
      multigene panel or familial variant test) were recruited into the MedSeq Project,
      a clinical trial of WGS. Results from panel genetic testing and WGS were
      compared. In 20 of 41 participants, panel genetic testing identified variants
      classified as pathogenic, likely pathogenic, or uncertain significance. WGS
      identified 19 of these 20 variants, but the variant detection algorithm missed a
      pathogenic 18 bp duplication in myosin binding protein C (MYBPC3) because of low
      coverage. In 3 individuals, WGS identified variants in genes implicated in
      cardiomyopathy but not included in prior panel testing: a pathogenic protein
      tyrosine phosphatase, non-receptor type 11 (PTPN11) variant and variants of
      uncertain significance in integrin-linked kinase (ILK) and filamin-C (FLNC). WGS
      also identified 84 secondary findings (mean=2 per person, range=0-6), which
      mostly defined carrier status for recessive conditions. CONCLUSIONS: WGS detected
      nearly all variants identified on panel testing, provided 1 new diagnostic
      finding, and allowed interrogation of posited disease genes. Several variants of
      uncertain clinical use and numerous secondary genetic findings were also
      identified. Whereas panel testing and WGS provided similar diagnostic yield, WGS
      offers the advantage of reanalysis over time to incorporate advances in
      knowledge, but requires expertise in genomic interpretation to appropriately
      incorporate WGS into clinical care. CLINICAL TRIAL REGISTRATION: URL:
      https://clinicaltrials.gov. Unique identifier: NCT01736566.

PMID- 29030402
TI  - Transcriptome and Functional Profile of Cardiac Myocytes Is Influenced by
      Biological Sex.
AB  - BACKGROUND: Although cardiovascular disease is the primary killer of women in the
      United States, women and female animals have traditionally been omitted from
      research studies. In reports that do include both sexes, significant sexual
      dimorphisms have been demonstrated in development, presentation, and outcome of
      cardiovascular disease. However, there is little understanding of the mechanisms
      underlying these observations. A more thorough understanding of sex-specific
      cardiovascular differences both at baseline and in disease is required to
      effectively consider and treat all patients with cardiovascular disease. METHODS
      AND RESULTS: We analyzed contractility in the whole rat heart, adult rat
      ventricular myocytes (ARVMs), and myofibrils from both sexes of rats and observed
      functional sex differences at all levels. Hearts and ARVMs from female rats
      displayed greater fractional shortening than males, and female ARVMs and
      myofibrils took longer to relax. To define factors underlying these functional
      differences, we performed an RNA sequencing experiment on ARVMs from male and
      female rats and identified ~600 genes were expressed in a sexually dimorphic
      manner. Further analysis revealed sex-specific enrichment of signaling pathways
      and key regulators. At the protein level, female ARVMs exhibited higher protein
      kinase A activity, consistent with pathway enrichment identified through RNA
      sequencing. In addition, activating the protein kinase A pathway diminished the
      contractile sexual dimorphisms previously observed. CONCLUSIONS: These data
      support the notion that sex-specific gene expression differences at baseline
      influence cardiac function, particularly through the protein kinase A pathway,
      and could potentially be responsible for differences in cardiovascular disease
      presentation and outcomes.

PMID- 29030404
TI  - A Smoking-Associated miRNA-mRNA Coexpression Network.

PMID- 29030405
TI  - Blood Pressure Genome-Wide Association Studies, Missing Heritability, and
      Omnigenics.

PMID- 29030406
TI  - Sex Determines Cardiac Myocyte Stretch and Relaxation.

PMID- 29030407
TI  - Hypertrophic Cardiomyopathy Gene Testing: Go Big?

PMID- 29030408
TI  - Unusual cause of opaque hemithorax.

PMID- 29030410
TI  - Shame and the vulnerable self in medical contexts: the compassionate solution.
AB  - Shame is a powerful experience that plays a vital role in a whole range of
      aspects of the clinical encounter. Shame experiences can have an impact on our
      psychological and physiological state and on how we experience ourselves, others
      and our relationships. The medical encounter is an obvious arena for shame
      because we are presenting (aspects of) our bodies and minds that can be seen as
      unattractive and undesirable, diseased, decayed and injured with the various
      excretions that typically might invite disgust. In contrast, experiences of
      compassion of acceptance, validation and kindness and can increase approach,
      openness and preparedness to engage with painful difficult scenarios. While shame
      is an experience that separates, segregates, marginalises and disengages people,
      caring and compassion facilitate integration, (re)connection and support. Given
      the potential opposite impacts of these different types of social experience,
      this paper will outline their evolutionary origins and compare and contrast them
      with particular reference to the medical context.

PMID- 29030403
TI  - New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000
      Individuals.
AB  - BACKGROUND: Genome-wide association studies have recently identified >400 loci
      that harbor DNA sequence variants that influence blood pressure (BP). Our earlier
      studies identified and validated 56 single nucleotide variants (SNVs) associated
      with BP from meta-analyses of exome chip genotype data. An additional 100
      variants yielded suggestive evidence of association. METHODS AND RESULTS: Here,
      we augment the sample with 140 886 European individuals from the UK Biobank, in
      whom 77 of the 100 suggestive SNVs were available for association analysis with
      systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one
      in individuals of European, South Asian, African, and Hispanic descent (pan
      ancestry, ~475 000), and the other in the subset of individuals of European
      descent (~423 000). Twenty-one SNVs were genome-wide significant (P<5*10-8) for
      BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940
      (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we
      identified a potentially independent novel BP-associated SNV, rs3416322
      (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported
      SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at
      3 loci are associated with other traits. One SNV with a minor allele frequency
      <0.01, (rs3025380 at DBH) was genome-wide significant. CONCLUSIONS: We report 4
      novel loci associated with BP regulation, and 1 independent variant at an
      established BP locus. This analysis highlights several candidate genes with
      variation that alter protein function or gene expression for potential follow-up.

PMID- 29030411
TI  - Global shortage of neonatal and paediatric antibiotic trials: rapid review.
AB  - OBJECTIVES: There have been few clinical trials (CTs) on antibiotics that inform
      neonatal and paediatric drug labelling. The rate of unlicensed and off-label
      prescribing in paediatrics remains high. It is unclear whether the current
      neonatal and paediatric antibiotic research pipeline is adequate to inform
      optimal drug dosing. Using the ClinicalTrials.gov registry, this review aims to
      establish the current global status of antibiotic CTs in children up to 18 years
      of age. METHODS: Studies were identified using key word searches of the
      ClinicalTrials.gov registry and were manually filtered using prespecified
      inclusion/exclusion criteria. RESULTS: 76 registered open CTs of antibiotics in
      children were identified globally; 23 (30%) were recruiting newborns (only 8
      (11%) included preterm neonates), 52 (68%) infants and toddlers, 58 (76%)
      children and 54 (71%) adolescents. The majority of registered trials were late
      phase (10 (15%) phase 3 and 23 (35%) phase 4/pharmacovigilance). Two-thirds were
      sponsored by non-profit organisations, compared with pharmaceutical companies (50
      (66%) vs 26 (34%), respectively). A greater proportion of non-profit funded
      trials were efficacy-based strategic trials (n=34, 68%), in comparison with
      industry-led trials, which were most often focused on safety or pharmacokinetic
      data (n=17, 65%). Only 2 of the 37 antibiotics listed on the May 2016 Pew
      Charitable Trusts antibiotic development pipeline, currently being studied in
      adults, appear to be currently recruiting in open paediatric CTs. CONCLUSIONS:
      This review highlights that very few paediatric antibiotic CTs are being
      conducted globally, especially in neonates. There is a striking disparity noted
      between antibiotic drug development programmes in adults and children.

PMID- 29030412
TI  - Strategies for developing sustainable health research capacity in low and middle
      income countries: a prospective, qualitative study investigating the barriers and
      enablers to locally led clinical trial conduct in Ethiopia, Cameroon and Sri
      Lanka.
AB  - OBJECTIVES: In 2013, the WHO stated that unless low-income and middle-income
      countries (LMICs) become producers of research, health goals would be hard to
      achieve. Among the capacities required to build a local evidence base, ability to
      conduct clinical trials is important. There is no evidence-based guidance for the
      best ways to develop locally led trial capacity. This research aims to identify
      the barriers and enablers to locally led clinical trial conduct in LMICs and
      determine strategies for their sustainable development. DESIGN: Prospective,
      multiple case study design consisting of interviews (n=34), focus group
      discussions (n=13) and process mapping exercises (n=10). SETTING: Case studies
      took place in Ethiopia (2011), Cameroon (2012) and Sri Lanka (2013).
      PARTICIPANTS: Local health researchers with previous experiences of clinical
      trials or stakeholders with an interest in trials were purposively selected
      through registration searches and snowball sampling (n=100). PRIMARY AND
      SECONDARY OUTCOME MEASURES: Discussion notes and transcripts were analysed using
      thematic coding analysis. Key themes and mechanisms were identified. RESULTS:
      Institutions and individuals were variably successful at conducting trials, but
      there were strong commonalities in the barriers and enablers across all levels
      and functions of the research systems. Transferable mechanisms were summarised
      into the necessary conditions for trial undertaking, which included: awareness of
      research, motivation, knowledge and technical skills, leadership capabilities,
      forming collaborations, inclusive trial operations, policy relevance and uptake
      and macro and institutional strengthening. CONCLUSIONS: Barriers and enablers to
      locally led trial undertaking exist at all levels and functions of LMIC research
      systems. Establishing the necessary conditions to facilitate this research will
      require multiple, coordinated interventions that seek to resolve them in a
      systemic manner. The strategies presented in the discussion provide an evidence
      based framework for a self-sustaining capacity development approach. This
      represents an important contribution to the literature that will be relevant for
      research funders, users and producers.

PMID- 29030409
TI  - Clinical relevance of androgen receptor alterations in prostate cancer.
AB  - Prostate cancer (PC) remains a leading cause of cancer-related deaths among men
      worldwide, despite continuously improved treatment strategies. Patients with
      metastatic disease are treated by androgen deprivation therapy (ADT) that with
      time results in the development of castration-resistant prostate cancer (CRPC)
      usually established as metastases within bone tissue. The androgen receptor (AR)
      transcription factor is the main driver of CRPC development and of acquired
      resistance to drugs given for treatment of CRPC, while a minority of patients
      have CRPC that is non-AR driven. Molecular mechanisms behind epithelial AR
      reactivation in CRPC include AR gene amplification and overexpression, AR
      mutations, expression of constitutively active AR variants, intra-tumoural and
      adrenal androgen synthesis and promiscuous AR activation by other factors. This
      review will summarize AR alterations of clinical relevance for patients with
      CRPC, with focus on constitutively active AR variants, their possible association
      with AR amplification and structural rearrangements as well as their ability to
      predict patient resistance to AR targeting drugs. The review will also discuss AR
      signalling in the tumour microenvironment and its possible relevance for
      metastatic growth and therapy.

PMID- 29030413
TI  - Patient-reported outcome measures for patients with meniscal tears: a systematic
      review of measurement properties and evaluation with the COSMIN checklist.
AB  - OBJECTIVE: Meniscal tears occur frequently in the population and the most common
      surgical treatment, arthroscopic partial meniscectomy, is performed in
      approximately two million cases worldwide each year. The purpose of this
      systematic review is to summarise and critically appraise the evidence for the
      use of patient-reported outcome measures (PROMs) in patients with meniscal tears.
      DESIGN: A systematic review was undertaken. Data on reported measurement
      properties were extracted and the quality of the studies appraised according to
      Consensus-based Standards for the Selection of Health Measurement Instruments.
      DATA SOURCES: A search of MEDLINE, Embase, AMED and PsycINFO, unlimited by
      language or publication date (last search 20 February 2017). ELIGIBILITY CRITERIA
      FOR SELECTING STUDIES: Development and validation studies reporting the
      measurement properties of PROMs in patients with meniscal tears were included.
      RESULTS: 11 studies and 10 PROMs were included. The overall quality of studies
      was poor. For measurement of symptoms and functional status, there is only very
      limited evidence supporting the selection of either the Lysholm Knee Scale,
      International Knee Documentation Committee Subjective Knee Form or the Dutch
      version of the Knee injury and Osteoarthritis Outcome Score. For measuring health
      related quality of life, only limited evidence supports the selection of the
      Western Ontario Meniscal Evaluation Tool (WOMET). Of all the PROMs evaluated,
      WOMET has the strongest evidence for content validity. CONCLUSION: For patients
      with meniscal tears, there is poor quality and incomplete evidence regarding the
      validity of the currently available PROMs. Further research is required to ensure
      these PROMs truly reflect the symptoms, function and quality of life of patients
      with meniscal tears. PROPERO REGISTRATION NUMBER: CRD42017056847.

PMID- 29030414
TI  - Longitudinal associations between marine omega-3 supplement users and coronary
      heart disease in a UK population-based cohort.
AB  - OBJECTIVES: Assess the association between marine omega-3 polyunsaturated fatty
      acid (n-3 PUFA) intake from supplements, mainly cod liver oil, and coronary heart
      disease (CHD) mortality. DESIGN: Prospective cohort study, with three exposure
      measurements over 22 years. SETTING: Norfolk-based European Prospective
      Investigation into Cancer (EPIC-Norfolk, UK). PARTICIPANTS: 22 035 men and women
      from the general population, 39-79 years at recruitment. EXPOSURE: Supplement use
      was assessed in three questionnaires (1993-1998; 2002-2004; 2004-2011).
      Participants were grouped into non-supplement users (NSU), n-3 PUFA supplement
      users (SU+n3) and non-n-3 PUFA supplement users (SU-n3). Cox regression adjusted
      for time-point specific variables: age, smoking, prevalent illnesses, body mass
      index, alcohol consumption, physical activity and season and baseline assessments
      of sex, social class, education and dietary intake (7-day diet diary). PRIMARY
      AND SECONDARY OUTCOME MEASURES: During a median of 19-year follow-up, 1562 CHD
      deaths were registered for 22 035 included participants. RESULTS: Baseline
      supplement use was not associated with CHD mortality, but baseline food and
      supplement intake of n-3 PUFA was inversely associated with CHD mortality after
      adjustment for fish consumption. Using time-varying covariate analysis,
      significant associations were observed for SU+n3 (HR: 0.74, 95% CI 0.66 to 0.84),
      but not for SU-n3 versus NSU. In further analyses, the association for SU+n3
      persisted in those who did not take other supplements (HR: 0.83, 95% CI 0.71 to
      0.97). Those who became SU+n3 over time or were consistent SU+n3 versus
      consistent NSU had a lower hazard of CHD mortality; no association with CHD was
      observed in those who stopped using n-3 PUFA-containing supplements. CONCLUSIONS:
      Recent use of n-3 PUFA supplements was associated with a lower hazard of CHD
      mortality in this general population with low fish consumption. Residual
      confounding cannot be excluded, but the findings observed may be explained by
      postulated biological mechanisms and the results were specific to SU+n3.

PMID- 29030415
TI  - Comorbidity and outcomes in traumatic brain injury: protocol for a systematic
      review on functional status and risk of death.
AB  - INTRODUCTION: Reports on the association between comorbidity and functional
      status and risk of death in patients with traumatic brain injury (TBI) have been
      inconsistent; it is currently unknown which additional clinical entities
      (comorbidities) have an adverse influence on the evolution of outcomes across the
      lifespan of men and women with TBI. The current protocol outlines a strategy for
      a systematic review of the current evidence examining the impact of comorbidity
      on functional status and early-term and late-term mortality, taking into account
      known risk factors of these adverse outcomes (ie, demographic (age and sex) and
      injury-related characteristics). METHODS AND ANALYSIS: A comprehensive search
      strategy for TBI prognosis, functional (cognitive and physical) status and
      mortality studies has been developed in collaboration with a medical information
      specialist of the large rehabilitation teaching hospital. All peer-reviewed
      English language studies with longitudinal design in adults with TBI of any
      severity, published from May 1997 to April 2017, found through Medline, Central,
      Embase, Scopus, PsycINFO and bibliographies of identified articles, will be
      considered eligible. Study quality will be assessed using published guidelines.
      ETHICS AND DISSEMINATION: The authors will publish findings from this review in a
      peer-reviewed scientific journal(s) and present the results at national and
      international conferences. This work aims to understand how comorbidity may
      contribute to adverse outcomes in TBI, to inform risk stratification of patients
      and guide the management of brain injury acutely and at the chronic stages
      postinjury on a population level. PROSPERO REGISTRATION NUMBER: CRD42017070033.

PMID- 29030417
TI  - Reply to 'Effects of sodium-glucose cotransporter 2 inhibitors on urinary
      excretion of intact and total angiotensinogen in patients with type 2 diabetes'
      by Yoshimoto et al.

PMID- 29030418
TI  - Short delay to initiate plasma exchange is the strongest predictor of outcome in
      severe attacks of NMO spectrum disorders.
AB  - INTRODUCTION: Severe attacks of neuromyelitis optica spectrum disorder (NMO-SD)
      are improved by plasma exchange (PLEX) given as an adjunctive therapy. Initial
      studies failed to demonstrate a delay of PLEX treatment influenced clinical
      outcome; however PLEX was always used late. We examine the clinical consequences
      of delay in PLEX initiation on severe optic neuritis and spinal cord attacks in
      NMO-SD. METHODS: All of our patients who suffered attacks of NMO-SD, treated in
      our centre by PLEX, were retrospectively considered for inclusion. Primary
      outcome was defined as complete improvement. Secondary poor/good outcomes were
      respectively defined to be the higher/lower third of Delta-Expanded Disability
      Status Scale (EDSS) (late minus baseline EDSS). Delays from clinical onset to
      PLEX initiation were categorised for multivariate analysis. RESULTS: Of the 60
      patients included, NMO-SD criteria (2015) were fulfilled in 92%. One hundred and
      fifteen attacks were included and received PLEX with a median of 7 days (0-54)
      after clinical onset. The probability to regain complete improvement continuously
      decreased from 50% for PLEX given at day 0 to 1%-5% after day 20. Through
      multivariate analysis, the baseline impairment and PLEX delay were associated
      with the probability to complete improvement (OR 5.3; 95% CI 1.8 to 15.9).
      Reducing the PLEX delay also influenced the good secondary outcome but not the
      poor secondary outcome. CONCLUSIONS: These results confirm an improved clinical
      benefit of early initiation of PLEX during severe attacks of NMO-SD. Perceiving
      PLEX as a rescue therapy only after steroid failure could be deleterious.

PMID- 29030419
TI  - Accuracy of clinical diagnosis of dementia with Lewy bodies: a systematic review
      and meta-analysis.
AB  - BACKGROUND: The diagnosis of dementia with Lewy bodies (DLB) is based on
      diagnostic clinical criteria, which were updated over the years. OBJECTIVE: To
      evaluate, through a systematic review, accuracy of the diagnostic criteria,
      testing a possible improvement over time. METHODS: We searched on MEDLINE and
      SCOPUS databases for studies reporting diagnostic parameters regarding the
      clinical diagnosis of DLB until October 2016. We performed meta-analysis, using a
      Bayesian approach, on those using pathological examination as gold standard,
      subclassified based on the different diagnostic criteria used. RESULTS: We
      selected 22 studies on 1585 patients. Pooled sensitivity, specificity and
      accuracy were 60.2%, 93.8%, 79.7%, respectively, for criteria antecedents to
      McKeith 1996. For McKeith 1996-possible, pooled sensitivity, specificity and
      accuracy were 65.6%, 80.6%, 77.9% in early stages and 72.3%, 64.3%, 66% in late
      stages, respectively. For McKeith 1996-probable, pooled sensitivity, specificity
      and accuracy were 19.4%, 95.1%, 77.7% in early stages and 48.6%, 88%, 79.2% in
      late stages, respectively. McKeith criteria 2005 were evaluated only in late
      stages: pooled sensitivity, specificity and accuracy were 91.3%, 66.7% and 81.6%,
      respectively, for possible diagnosis (only one study) and 88.3%, 80.8%, 90.7% for
      probable diagnosis, decreasing to 85.6%, 77.1% and 81.7% if only considering
      clinical settings focused on dementia diagnosis and care. CONCLUSIONS AND
      RELEVANCE: Diagnostic criteria have become more sensitive and less specific over
      time, without substantial change in the accuracy. Based on current data, about
      20% of DLB diagnosis are incorrect. Future studies are needed to evaluate if the
      recently released revised consensus criteria will improve the diagnostic accuracy
      of DLB.

PMID- 29030416
TI  - Genome-Wide Identification of Medicago Peptides Involved in Macronutrient
      Responses and Nodulation.
AB  - Growing evidence indicates that small, secreted peptides (SSPs) play critical
      roles in legume growth and development, yet the annotation of SSP-coding genes is
      far from complete. Systematic reannotation of the Medicago truncatula genome
      identified 1,970 homologs of established SSP gene families and an additional
      2,455 genes that are potentially novel SSPs, previously unreported in the
      literature. The expression patterns of known and putative SSP genes based on 144
      RNA sequencing data sets covering various stages of macronutrient deficiencies
      and symbiotic interactions with rhizobia and mycorrhiza were investigated.
      Focusing on those known or suspected to act via receptor-mediated signaling, 240
      nutrient-responsive and 365 nodulation-responsive Signaling-SSPs were identified,
      greatly expanding the number of SSP gene families potentially involved in
      acclimation to nutrient deficiencies and nodulation. Synthetic peptide
      applications were shown to alter root growth and nodulation phenotypes, revealing
      additional regulators of legume nutrient acquisition. Our results constitute a
      powerful resource enabling further investigations of specific SSP functions via
      peptide treatment and reverse genetics.

PMID- 29030420
TI  - New biomarker for acute ischaemic stroke: plasma glycogen phosphorylase isoenzyme
      BB.
AB  - BACKGROUND: Glycogen phosphorylase is the key enzyme that breaks down glycogen to
      yield glucose-1-phosphate in order to restore depleted energy stores during
      cerebral ischaemia. We sought to determine whether plasma levels of glycogen
      phosphorylase BB (GPBB) isoform increased in patients with acute ischaemic stroke
      (AIS). METHODS: We studied plasma GPBB levels within 12 hours and again at 48+/
      24 hours of symptom onset in 172 patients with imaging-confirmed AIS and 133
      stroke-free individuals. We determined the ability of plasma GPBB to discriminate
      between cases and controls and examined the predictive value of plasma GPBB for
      90-day functional outcome, 90-day survival and acute lesion volumes on
      neuroimaging. RESULTS: The mean (SD) GPBB levels were higher in cases (46.3+/
      38.6 ng/mL at first measurement and 38.6+/-36.5 ng/mL at second measurement) than
      in controls (4.1+/-7.6 ng/mL, p<0.01 for both). The area under the receiver
      operating characteristic (ROC) curve for case-control discrimination based on
      first GPBB measurement was 0.96 (95% CI 0.93 to 0.98). The sensitivity and
      specificity based on optimal operating point on the ROC curve (7.0 ng/mL) were
      both 93%. GPBB levels increased in 90% of patients with punctate infarcts (<1.5
      mL) and in all patients admitted within the first 4.5 hours of onset. There was
      no correlation between GPBB concentration and either clinical outcome or acute
      infarct volume. CONCLUSION: GPBB demonstrates robust response to acute ischaemia
      and high sensitivity for small infarcts. If confirmed in more diverse populations
      that also include stroke mimics, GPBB could find utility as a stand-alone marker
      for acute brain ischaemia.

PMID- 29030421
TI  - Serotonin transporter gene polymorphisms may be associated with poststroke
      neurological recovery after escitalopram use.
AB  - OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) putatively improve
      neurological recovery after stroke. We aimed to investigate whether serotonin
      transporter (SERT) gene polymorphisms are related to the responsiveness to SSRIs
      in the poststroke neurological recovery. METHODS: This was a post hoc analysis of
      the EMOTION study (ClinicalTrials.gov NCT01278498), a randomised, placebo
      controlled, double-blind trial examining the efficacy of escitalopram on
      emotional and neurological disturbances after acute stroke. Patients with
      no/minimal disability initially (modified Rankin Scale (mRS) 0-1) were excluded.
      Of the participants, 301 underwent genetic studies of the STin2 (a variable
      number tandem repeat (VNTR) in intron 2) (STin2 12/10 and STin2 12/12 genotypes)
      and 5-HTTLPR (a variable-length repeat in the promoter region) polymorphisms of
      SERT. We explored whether neurological function (National Institutes of Health
      Stroke Scale (NIHSS) score and mRS) at 3 months would differ according to SERT
      polymorphisms within each treatment arm (escitalopram and placebo). RESULTS:
      Among the escitalopram users (n=159), neurological function in subjects with
      STin2 12/10 (n=29) improved significantly more than that in STin2 12/12 carriers
      (n=130) at 3 months. After adjusting for age, initial NIHSS and depression, STin2
      12/10 independently predicted a good clinical outcome (mRS 0-1) (OR 2.99, 95% CI
      1.04 to 8.58) at 3 months. However, differences between STin2 polymorphisms were
      not shown in the placebo group (n=142). 5-HTTLPR polymorphisms were not
      associated with neurological recovery in any treatment group. CONCLUSION: STin2
      VNTR polymorphisms may be associated with poststroke neurological recovery after
      SSRI therapy. Further studies are needed to identify the role of serotonin in
      neurological recovery after stroke.

PMID- 29030422
TI  - Outcome of intracerebral haemorrhage related to non-vitamin K antagonists oral
      anticoagulants versus vitamin K antagonists: a comprehensive systematic review
      and meta-analysis.
AB  - INTRODUCTION: The characteristics and natural history of acute non-vitamin K
      antagonists oral anticoagulants (NOAC)-associated intracerebral haemorrhage (ICH)
      are largely unknown. We performed a comprehensive systematic review and meta
      analysis to compare baseline ICH volume, haematoma expansion and clinical
      outcomes between NOAC-ICH versus vitamin K antagonists-ICH (VKA-ICH). METHODS: We
      searched PubMed and conference abstracts for observational studies comparing
      baseline characteristics and outcomes in patients with NOAC-ICH versus VKA-ICH
      using an appropriate keyword/MeSH term search strategy. Data were extracted
      following PRISMA and MOOSE guidelines. The main outcome measures were mortality
      and unfavourable functional outcome (modified Rankin Score: 4-6) at discharge and
      at 3 months, as well as ICH volumes and haematoma expansion rates in the two
      groups. Random-effects models with DerSimonian-Laird weights were used for pooled
      estimates calculation. RESULTS: Twelve studies including 393 NOAC-ICH and 3482
      VKA-ICH were pooled in meta-analysis. There was no difference in mean ICH-volume
      between the two groups (standard mean difference: -0.24; 95% CI -0.52 to 0.04,
      p=0.093). The rates of haematoma expansion were comparable in NOAC-ICH versus VKA
      ICH (OR: 0.76; 95% CI 0.49 to 1.19, p=0.236). We did not find any difference
      between patients with NOAC-ICH versus VKA-ICH in all-cause mortality at discharge
      (OR: 0.66; 95% CI 0.42 to 1.05, p=0.077) and unfavourable functional outcome at
      discharge (OR: 0.77; 95% CI 0.41 to 1.44, p=0.413). The 3-month outcome was also
      comparable between the two ICH groups. Moderate-to-substantial statistical
      heterogeneity was noted. CONCLUSION: Our results confirm that ICH volume,
      haematoma expansion, mortality and functional outcome appear to be similar for
      NOAC-ICH versus VKA-ICH. Large prospective cohorts and updated meta-analyses are
      needed to provide more precise estimates.

PMID- 29030423
TI  - Graphics and statistics for cardiology: designing effective tables for
      presentation and publication.
AB  - Research is of little use if its results are not effectively communicated. Data
      visualised in tables (and graphs) are key components in any scientific report,
      but their design leaves much to be desired. This article focuses on table design,
      following two general principles: clear vision and clear understanding. Clear
      vision is achieved by maximising the signal to noise ratio. In a table, the
      signal is the data in the form of numbers, and the noise is the support structure
      necessary to interpret the numbers. Clear understanding is achieved when the
      story in the data is told effectively, through organisation of the data and use
      of text. These principles are illustrated by original and improved tables from
      recent publications. Two special cases are discussed separately: tables produced
      by the pharmaceutical industry (in clinical study reports and reports to data
      safety monitoring boards), and study flow diagrams as proposed by the
      Consolidated Standards of Reporting Trials and Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses initiatives.

PMID- 29030424
TI  - Stable coronary syndromes: pathophysiology, diagnostic advances and therapeutic
      need.
AB  - The diagnostic management of patients with angina pectoris typically centres on
      the detection of obstructive epicardial CAD, which aligns with evidence-based
      treatment options that include medical therapy and myocardial revascularisation.
      This clinical paradigm fails to account for the considerable proportion
      (approximately one-third) of patients with angina in whom obstructive CAD is
      excluded. This common scenario presents a diagnostic conundrum whereby angina
      occurs but there is no obstructive CAD (ischaemia and no obstructive coronary
      artery disease-INOCA). We review new insights into the pathophysiology of angina
      whereby myocardial ischaemia results from a deficient supply of oxygenated blood
      to the myocardium, due to various combinations of focal or diffuse epicardial
      disease (macrovascular), microvascular dysfunction or both. Macrovascular disease
      may be due to the presence of obstructive CAD secondary to atherosclerosis, or
      may be dynamic due to a functional disorder (eg, coronary artery spasm,
      myocardial bridging). Pathophysiology of coronary microvascular disease may
      involve anatomical abnormalities resulting in increased coronary resistance, or
      functional abnormalities resulting in abnormal vasomotor tone. We consider novel
      clinical diagnostic techniques enabling new insights into the causes of angina
      and appraise the need for improved therapeutic options for patients with INOCA.
      We conclude that the taxonomy of stable CAD could improve to better reflect the
      heterogeneous pathophysiology of the coronary circulation. We propose the term
      'stable coronary syndromes' (SCS), which aligns with the well-established
      terminology for 'acute coronary syndromes'. SCS subtends a clinically relevant
      classification that more fully encompasses the different diseases of the
      epicardial and microvascular coronary circulation.

PMID- 29030425
TI  - Quantitative time-course metabolomics in human red blood cells reveal the
      temperature dependence of human metabolic networks.
AB  - The temperature dependence of biological processes has been studied at the levels
      of individual biochemical reactions and organism physiology (e.g. basal metabolic
      rates) but has not been examined at the metabolic network level. Here, we used a
      systems biology approach to characterize the temperature dependence of the human
      red blood cell (RBC) metabolic network between 4 and 37  degrees C through
      absolutely quantified exo- and endometabolomics data. We used an Arrhenius-type
      model (Q10) to describe how the rate of a biochemical process changes with every
      10  degrees C change in temperature. Multivariate statistical analysis of the
      metabolomics data revealed that the same metabolic network-level trends
      previously reported for RBCs at 4  degrees C were conserved but accelerated with
      increasing temperature. We calculated a median Q10 coefficient of 2.89 +/- 1.03,
      within the expected range of 2-3 for biological processes, for 48 individual
      metabolite concentrations. We then integrated these metabolomics measurements
      into a cell-scale metabolic model to study pathway usage, calculating a median
      Q10 coefficient of 2.73 +/- 0.75 for 35 reaction fluxes. The relative fluxes
      through glycolysis and nucleotide metabolism pathways were consistent across the
      studied temperature range despite the non-uniform distributions of Q10
      coefficients of individual metabolites and reaction fluxes. Together, these
      results indicate that the rate of change of network-level responses to
      temperature differences in RBC metabolism is consistent between 4 and 37  degrees
      C. More broadly, we provide a baseline characterization of a biochemical network
      given no transcriptional or translational regulation that can be used to explore
      the temperature dependence of metabolism.

PMID- 29030426
TI  - Molecular insights into the m-AAA protease-mediated dislocation of transmembrane
      helices in the mitochondrial inner membrane.
AB  - Protein complexes involved in respiration, ATP synthesis, and protein import
      reside in the mitochondrial inner membrane; thus, proper regulation of these
      proteins is essential for cell viability. The m-AAA protease, a conserved hetero
      hexameric AAA (ATPase associated with diverse cellular activities) protease,
      composed of the Yta10 and Yta12 proteins, regulates mitochondrial proteostasis by
      mediating protein maturation and degradation. It also recognizes and mediates the
      dislocation of membrane-embedded substrates, including foreign transmembrane (TM)
      segments, but the molecular mechanism involved in these processes remains
      elusive. This study investigated the role of the TM domains in the m-AAA protease
      by systematic replacement of one TM domain at a time in yeast. Our data indicated
      that replacement of the Yta10 TM2 domain abolishes membrane dislocation for only
      a subset of substrates, whereas replacement of the Yta12 TM2 domain impairs
      membrane dislocation for all tested substrates, suggesting different roles of the
      TM domains in each m-AAA protease subunit. Furthermore, m-AAA protease-mediated
      membrane dislocation was impaired in the presence of a large downstream
      hydrophilic moiety in a membrane substrate. This finding suggested that the m-AAA
      protease cannot dislocate large hydrophilic domains across the membrane,
      indicating that the membrane dislocation probably occurs in a lipid environment.
      In summary, this study highlights previously underappreciated biological roles of
      TM domains of the m-AAA proteases in mediating the recognition and dislocation of
      membrane-embedded substrates.

PMID- 29030427
TI  - Structural insights into marine carbohydrate degradation by family GH16 kappa
      carrageenases.
AB  - Carrageenans are sulfated alpha-1,3-beta-1,4-galactans found in the cell wall of
      some red algae that are practically valuable for their gelation and biomimetic
      properties but also serve as a potential carbon source for marine bacteria.
      Carbohydrate degradation has been studied extensively for terrestrial
      plant/bacterial systems, but sulfation is not present in these cases, meaning the
      marine enzymes used to degrade carrageenans must possess unique features to
      recognize these modifications. To gain insights into these features, we have
      focused on kappa-carrageenases from two distant bacterial phyla, which belong to
      glycoside hydrolase family 16 and cleave the beta-1,4 linkage of kappa
      carrageenan. We have solved the crystal structure of the catalytic module of
      ZgCgkA from Zobellia galactanivorans at 1.66 A resolution and compared it with
      the only other structure available, that of PcCgkA from Pseudoalteromonas
      carrageenovora 9T (ATCC 43555T). We also describe the first substrate complex in
      the inactivated mutant form of PcCgkA at 1.7 A resolution. The structural and
      biochemical comparison of these enzymes suggests key determinants that underlie
      the functional properties of this subfamily. In particular, we identified several
      arginine residues that interact with the polyanionic substrate, and confirmed the
      functional relevance of these amino acids using a targeted mutagenesis strategy.
      These results give new insight into the diversity of the kappa-carrageenase
      subfamily. The phylogenetic analyses show the presence of several distinct clades
      of enzymes that relate to differences in modes of action or subtle differences
      within the same substrate specificity, matching the hybrid character of the kappa
      carrageenan polymer.

PMID- 29030428
TI  - A retractable lid in lecithin:cholesterol acyltransferase provides a structural
      mechanism for activation by apolipoprotein A-I.
AB  - Lecithin:cholesterol acyltransferase (LCAT) plays a key role in reverse
      cholesterol transport by transferring an acyl group from phosphatidylcholine to
      cholesterol, promoting the maturation of high-density lipoproteins (HDL) from
      discoidal to spherical particles. LCAT is activated through an unknown mechanism
      by apolipoprotein A-I (apoA-I) and other mimetic peptides that form a belt around
      HDL. Here, we report the crystal structure of LCAT with an extended lid that
      blocks access to the active site, consistent with an inactive conformation.
      Residues Thr-123 and Phe-382 in the catalytic domain form a latch-like
      interaction with hydrophobic residues in the lid. Because these residues are
      mutated in genetic disease, lid displacement was hypothesized to be an important
      feature of apoA-I activation. Functional studies of site-directed mutants
      revealed that loss of latch interactions or the entire lid enhanced activity
      against soluble ester substrates, and hydrogen-deuterium exchange (HDX) mass
      spectrometry revealed that the LCAT lid is extremely dynamic in solution. Upon
      addition of a covalent inhibitor that mimics one of the reaction intermediates,
      there is an overall decrease in HDX in the lid and adjacent regions of the
      protein, consistent with ordering. These data suggest a model wherein the active
      site of LCAT is shielded from soluble substrates by a dynamic lid until it
      interacts with HDL to allow transesterification to proceed.

PMID- 29030429
TI  - Activating mutations in quorum-sensing regulator Rgg2 and its conformational
      flexibility in the absence of an intermolecular disulfide bond.
AB  - Rap/Rgg/NprR/PlcR/PrgX (RRNPP) quorum-sensing systems use extracellular peptide
      pheromones that are detected by cytoplasmic receptors to regulate gene expression
      in firmicute bacteria. Rgg-type receptors are allosterically regulated through
      direct pheromone binding to control transcriptional activity; however, the
      receptor activation mechanism remains poorly understood. Previous work has
      identified a disulfide bond between Cys-45 residues within the homodimer
      interface of Rgg2 from Streptococcus dysgalactiae (Rgg2Sd). Here, we compared two
      Rgg2Sd(C45S) X-ray crystal structures with that of wild-type Rgg2Sd and found
      that in the absence of the intermolecular disulfide, the Rgg2Sd dimer interface
      is destabilized and Rgg2Sd can adopt multiple conformations. One conformation
      closely resembled the "disulfide-locked" Rgg2Sd secondary and tertiary
      structures, but another displayed more extensive rigid-body shifts as well as
      dramatic secondary structure changes. In parallel experiments, a genetic screen
      was used to identify mutations in rgg2 of Streptococcus pyogenes (rgg2Sp ) that
      conferred pheromone-independent transcriptional activation of an Rgg2-stimulated
      promoter. Eight mutations yielding constitutive Rgg2 activity, designated
      Rgg2Sp*, were identified, and five of them clustered in or near an Rgg2 region
      that underwent conformational changes in one of the Rgg2Sd(C45S) crystal
      structures. The Rgg2Sp* mutations increased Rgg2Sp sensitivity to pheromone and
      pheromone variants while displaying decreased sensitivity to the Rgg2 antagonist
      cyclosporine A. We propose that Rgg2Sp* mutations invoke shifts in free-energy
      bias to favor the active state of the protein. Finally, we present evidence for
      an electrostatic interaction between an N-terminal Asp of the pheromone and Arg
      153 within the proposed pheromone-binding pocket of Rgg2Sp.

PMID- 29030430
TI  - Direct binding to integrins and loss of disulfide linkage in interleukin-1beta
      (IL-1beta) are involved in the agonistic action of IL-1beta.
AB  - There is a strong link between integrins and interleukin-1beta (IL-1beta), but
      the specifics of the role of integrins in IL-1beta signaling are unclear. We
      describe that IL-1beta specifically bound to integrins alphavbeta3 and
      alpha5beta1. The E128K mutation in the IL1R-binding site enhanced integrin
      binding. We studied whether direct integrin binding is involved in IL-1beta
      signaling. We compared sequences of IL-1beta and IL-1 receptor antagonist
      (IL1RN), which is an IL-1beta homologue but has no agonistic activity. Several
      surface-exposed Lys residues are present in IL-1beta, but not in IL1RN. A
      disulfide linkage is present in IL1RN, but is not in IL-1beta because of natural
      C117F mutation. Substitution of the Lys residues to Glu markedly reduced integrin
      binding of E128K IL-1beta, suggesting that the Lys residues mediate integrin
      binding. The Lys mutations reduced, but did not completely abrogate, agonistic
      action of IL-1beta. We studied whether the disulfide linkage plays a role in
      agonistic action of IL-1beta. Reintroduction of the disulfide linkage by the
      F117C mutation did not affect agonistic activity of WT IL-1beta, but effectively
      reduced the remaining agonistic activity of the Lys mutants. Also, deletion of
      the disulfide linkage in IL1RN by the C116F mutation did not make it agonistic.
      We propose that the direct binding to IL-1beta to integrins is primarily
      important for agonistic IL-1beta signaling, and that the disulfide linkage
      indirectly affects signaling by blocking conformational changes induced by weak
      integrin binding to the Lys mutants. The integrin-IL-1beta interaction is a
      potential target for drug discovery.

PMID- 29030431
TI  - Distinctive Modulation of Dopamine Release in the Nucleus Accumbens Shell
      Mediated by Dopamine and Acetylcholine Receptors.
AB  - Nucleus accumbens (NAc) shell shows unique dopamine (DA) signals in vivo and
      plays a unique role in DA-dependent behaviors such as reward-motivated learning
      and the response to drugs of abuse. A disynaptic mechanism for DA release was
      reported and shown to require synchronized firing of cholinergic interneurons
      (CINs) and activation of nicotinic acetylcholine (ACh) receptors (nAChRs) in DA
      neuron (DAN) axons. The properties of this disynaptic mechanism of DA
      transmission are not well understood in the NAc shell. In this study, in vitro
      fast-scan cyclic voltammetry was used to examine the modulation of DA
      transmission evoked by CINs firing in the shell of mice and compared with other
      striatal regions. We found that DA signals in the shell displayed significant
      degree of summation in response to train stimulation of CINs, contrary to core
      and dorsal striatum. The summation was amplified by a D2-like receptor antagonist
      and experiments with mice with targeted deletion of D2 receptors to DANs or CINs
      revealed that D2 receptors in CINs mediate a fast inhibition observed within 100
      ms of the first pulse, whereas D2 autoreceptors in DAN terminals are engaged in a
      slower inhibition that peaks at ~500 ms. ACh also contributes to the use
      dependent inhibition of DA release through muscarinic receptors only in the
      shell, where higher activity of acetylcholinesterase minimizes nAChR
      desensitization and promotes summation. These findings show that DA signals are
      modulated differentially by endogenous DA and ACh in the shell, which may
      underlie the unique features of shell DA signals in vivoSIGNIFICANCE STATEMENT
      The present study reports that dopamine (DA) release evoked by activation of
      cholinergic interneurons displays a high degree of summation in the shell and
      shows unique modulation by endogenous DA and acetylcholine. Desensitization of
      nicotinic receptors, which is a prevailing mechanism for use-dependent inhibition
      in the nucleus accumbens core and dorsal striatum, is also minimal in the shell
      in part due to elevated acetylcholinesterase activity. This distinctive
      modulation of DA transmission in the shell may have functional implications in
      the acquisition of reward-motivated behaviors and reward seeking.

PMID- 29030432
TI  - Protein Kinase A Deregulation in the Medial Prefrontal Cortex Impairs Working
      Memory in Murine Oligophrenin-1 Deficiency.
AB  - Classical and systems genetics have identified wide networks of genes associated
      with cognitive and neurodevelopmental diseases. In parallel to deciphering the
      role of each of these genes in neuronal or synaptic function, evaluating the
      response of neuronal and molecular networks to gene loss of function could reveal
      some pathophysiological mechanisms potentially accessible to nongenetic
      therapies. Loss of function of the Rho-GAP oligophrenin-1 is associated with
      cognitive impairments in both human and mouse. Upregulation of both PKA and ROCK
      has been reported in Ophn1-/y mice, but it remains unclear whether kinase
      hyperactivity contributes to the behavioral phenotypes. In this study, we
      thoroughly characterized a prominent perseveration phenotype displayed by Ophn1
      deficient mice using a Y-maze spatial working memory (SWM) test. We report that
      Ophn1 deficiency in the mouse generated severe cognitive impairments,
      characterized by both a high occurrence of perseverative behaviors and a lack of
      deliberation during the SWM test. In vivo and in vitro pharmacological
      experiments suggest that PKA dysregulation in the mPFC underlies cognitive
      dysfunction in Ophn1-deficient mice, as assessed using a delayed spatial
      alternation task results. Functionally, mPFC neuronal networks appeared to be
      affected in a PKA-dependent manner, whereas hippocampal-PFC projections involved
      in SWM were not affected in Ophn1-/y mice. Thus, we propose that discrete gene
      mutations in intellectual disability might generate "secondary"
      pathophysiological mechanisms, which are prone to become pharmacological targets
      for curative strategies in adult patients.SIGNIFICANCE STATEMENT Here we report
      that Ophn1 deficiency generates severe impairments in performance at spatial
      working memory tests, characterized by a high occurrence of perseverative
      behaviors and a lack of decision making. This cognitive deficit is consecutive to
      PKA deregulation in the mPFC that prevents Ophn1 KO mice to exploit a correctly
      acquired rule. Functionally, mPFC neuronal networks appear to be affected in a
      PKA-dependent manner, whereas behaviorally important hippocampal projections were
      preserved by the mutation. Thus, we propose that discrete gene mutations in
      intellectual disability can generate "secondary" pathophysiological mechanisms
      prone to become pharmacological targets for curative strategies in adults.

PMID- 29030433
TI  - Dysregulation of the Mitochondrial Unfolded Protein Response Induces Non
      Apoptotic Dopaminergic Neurodegeneration in C. elegans Models of Parkinson's
      Disease.
AB  - Due to environmental insult or innate genetic deficiency, protein folding
      environments of the mitochondrial matrix are prone to dysregulation, prompting
      the activation of a specific organellar stress-response mechanism, the
      mitochondrial unfolded protein response (UPRMT). In Caenorhabditis elegans,
      mitochondrial damage leads to nuclear translocation of the ATFS-1 transcription
      factor to activate the UPRMT After short-term acute stress has been mitigated,
      the UPRMT is eventually suppressed to restore homeostasis to C. elegans
      hermaphrodites. In contrast, and reflective of the more chronic nature of
      progressive neurodegenerative disorders such as Parkinson's disease (PD), here,
      we report the consequences of prolonged, cell-autonomous activation of the UPRMT
      in C. elegans dopaminergic neurons. We reveal that neuronal function and
      integrity decline rapidly with age, culminating in activity-dependent, non
      apoptotic cell death. In a PD-like context wherein transgenic nematodes express
      the Lewy body constituent protein alpha-synuclein (alphaS), we not only find that
      this protein and its PD-associated disease variants have the capacity to induce
      the UPRMT, but also that coexpression of alphaS and ATFS-1-associated
      dysregulation of the UPRMT synergistically potentiate dopaminergic neurotoxicity.
      This genetic interaction is in parallel to mitophagic pathways dependent on the
      C. elegans PINK1 homolog, which is necessary for cellular resistance to chronic
      malfunction of the UPRMT Given the increasingly recognized role of mitochondrial
      quality control in neurodegenerative diseases, these studies illustrate, for the
      first time, an insidious aspect of mitochondrial signaling in which the UPRMT
      pathway, under disease-associated, context-specific dysregulation, exacerbates
      disruption of dopaminergic neurons in vivo, resulting in the neurodegeneration
      characteristic of PD.SIGNIFICANCE STATEMENT Disruptions or alterations in the
      activation of pathways that regulate mitochondrial quality control have been
      linked to neurodegenerative diseases due in part to the central role of
      mitochondria in metabolism, ROS regulation, and proteostasis. The extent to which
      these pathways, including the mitochondrial unfolded protein response (UPRMT) and
      mitophagy, are active may predict severity and progression of these disorders, as
      well as sensitivity to compounding stressors. Furthermore, therapeutic strategies
      that aim to induce these pathways may benefit from increased study into cellular
      responses that arise from long-term or ectopic stimulation, especially in
      neuronal compartments. By demonstrating the detrimental consequences of prolonged
      cellular activation of the UPRMT, we provide evidence that this pathway is not a
      universally beneficial mechanism because dysregulation has neurotoxic
      consequences.

PMID- 29030434
TI  - Cadherin-10 Maintains Excitatory/Inhibitory Ratio through Interactions with
      Synaptic Proteins.
AB  - Appropriate excitatory/inhibitory (E/I) balance is essential for normal cortical
      function and is altered in some psychiatric disorders, including autism spectrum
      disorders (ASDs). Cell-autonomous molecular mechanisms that control the balance
      of excitatory and inhibitory synapse function remain poorly understood; no
      proteins that regulate excitatory and inhibitory synapse strength in a
      coordinated reciprocal manner have been identified. Using super-resolution
      imaging, electrophysiology, and molecular manipulations, we show that cadherin
      10, encoded by CDH10 within the ASD risk locus 5p14.1, maintains both excitatory
      and inhibitory synaptic scaffold structure in cultured cortical neurons from rats
      of both sexes. Cadherin-10 localizes to both excitatory and inhibitory synapses
      in neocortex, where it is organized into nanoscale puncta that influence the size
      of their associated PSDs. Knockdown of cadherin-10 reduces excitatory but
      increases inhibitory synapse size and strength, altering the E/I ratio in
      cortical neurons. Furthermore, cadherin-10 exhibits differential participation in
      complexes with PSD-95 and gephyrin, which may underlie its role in maintaining
      the E/I ratio. Our data provide a new mechanism whereby a protein encoded by a
      common ASD risk factor controls E/I ratios by regulating excitatory and
      inhibitory synapses in opposing directions.SIGNIFICANCE STATEMENT The correct
      balance between excitatory/inhibitory (E/I) is crucial for normal brain function
      and is altered in psychiatric disorders such as autism. However, the molecular
      mechanisms that underlie this balance remain elusive. To address this, we studied
      cadherin-10, an adhesion protein that is genetically linked to autism and
      understudied at the cellular level. Using a combination of advanced microscopy
      techniques and electrophysiology, we show that cadherin-10 forms nanoscale puncta
      at excitatory and inhibitory synapses, maintains excitatory and inhibitory
      synaptic structure, and is essential for maintaining the correct balance between
      excitation and inhibition in neuronal dendrites. These findings reveal a new
      mechanism by which E/I balance is controlled in neurons and may bear relevance to
      synaptic dysfunction in autism.

PMID- 29030435
TI  - Dissociation of Self-Motion and Object Motion by Linear Population Decoding That
      Approximates Marginalization.
AB  - We use visual image motion to judge the movement of objects, as well as our own
      movements through the environment. Generally, image motion components caused by
      object motion and self-motion are confounded in the retinal image. Thus, to
      estimate heading, the brain would ideally marginalize out the effects of object
      motion (or vice versa), but little is known about how this is accomplished
      neurally. Behavioral studies suggest that vestibular signals play a role in
      dissociating object motion and self-motion, and recent computational work
      suggests that a linear decoder can approximate marginalization by taking
      advantage of diverse multisensory representations. By measuring responses of MSTd
      neurons in two male rhesus monkeys and by applying a recently-developed method to
      approximate marginalization by linear population decoding, we tested the
      hypothesis that vestibular signals help to dissociate self-motion and object
      motion. We show that vestibular signals stabilize tuning for heading in neurons
      with congruent visual and vestibular heading preferences, whereas they stabilize
      tuning for object motion in neurons with discrepant preferences. Thus, vestibular
      signals enhance the separability of joint tuning for object motion and self
      motion. We further show that a linear decoder, designed to approximate
      marginalization, allows the population to represent either self-motion or object
      motion with good accuracy. Decoder weights are broadly consistent with a readout
      strategy, suggested by recent computational work, in which responses are decoded
      according to the vestibular preferences of multisensory neurons. These results
      demonstrate, at both single neuron and population levels, that vestibular signals
      help to dissociate self-motion and object motion.SIGNIFICANCE STATEMENT The brain
      often needs to estimate one property of a changing environment while ignoring
      others. This can be difficult because multiple properties of the environment may
      be confounded in sensory signals. The brain can solve this problem by
      marginalizing over irrelevant properties to estimate the property-of-interest. We
      explore this problem in the context of self-motion and object motion, which are
      inherently confounded in the retinal image. We examine how diversity in a
      population of multisensory neurons may be exploited to decode self-motion and
      object motion from the population activity of neurons in macaque area MSTd.

PMID- 29030436
TI  - A Mutator Phenotype Promoting the Emergence of Spontaneous Oxidative Stress
      Resistant Mutants in Campylobacter jejuni.
AB  - Campylobacter jejuni is a leading cause of foodborne illnesses worldwide. As a
      microaerophilic organism, C. jejuni must be able to defend against oxidative
      stress encountered both in the host and in the environment. How Campylobacter
      utilizes a mutation-based mechanism for adaptation to oxidative stress is still
      unknown. Here we present a previously undescribed phenotypic and genetic
      mechanism that promotes the emergence of oxidative stress-resistant mutants.
      Specifically, we showed that a naturally occurring mutator phenotype, resulting
      from a loss of function mutation in the DNA repair enzyme MutY, increased
      oxidative stress resistance (OXR) in C. jejuni We further demonstrated that MutY
      malfunction did not directly contribute to the OXR phenotype but increased the
      spontaneous mutation rate in the peroxide regulator gene perR, which functions as
      a repressor for multiple genes involved in oxidative stress resistance. Mutations
      in PerR resulted in loss of its DNA binding function and derepression of PerR
      controlled oxidative stress defense genes, thereby conferring an OXR phenotype
      and facilitating Campylobacter survival under oxidative stress. These findings
      reveal a new mechanism that promotes the emergence of spontaneous OXR mutants in
      bacterial organisms.IMPORTANCE Although a mutator phenotype has been shown to
      promote antibiotic resistance in many bacterial species, little is known about
      its contribution to the emergence of OXR mutants. This work describes the link
      between a mutator phenotype and the enhanced emergence of OXR mutants as well as
      its underlying mechanism involving DNA repair and mutations in PerR. Since DNA
      repair systems and PerR are well conserved in many bacterial species, especially
      in Gram positives, the same mechanism may operate in multiple bacterial species.
      Additionally, we developed a novel method that allows for rapid quantification of
      spontaneous OXR mutants in a bacterial population. This method represents a
      technical innovation and may also be applied to other bacterial species. These
      findings significantly advance our understanding of bacterial mechanisms for
      survival under oxidative stress.

PMID- 29030437
TI  - Formation of Staphylococcus aureus Biofilm in the Presence of Sublethal
      Concentrations of Disinfectants Studied via a Transcriptomic Analysis Using
      Transcriptome Sequencing (RNA-seq).
AB  - Staphylococcus aureus is a common biofilm-forming pathogen. Low doses of
      disinfectants have previously been reported to promote biofilm formation and to
      increase virulence. The aim of this study was to use transcriptome sequencing
      (RNA-seq) analysis to investigate global transcriptional changes in S. aureus in
      response to sublethal concentrations of the commonly used food industry
      disinfectants ethanol (EtOH) and chloramine T (ChT) and their combination
      (EtOH_ChT) in order to better understand the effects of these agents on biofilm
      formation. Treatment with EtOH and EtOH_ChT resulted in more significantly
      altered expression profiles than treatment with ChT. Our results revealed that
      EtOH and EtOH_ChT treatments enhanced the expression of genes responsible for
      regulation of gene expression (sigB), cell surface factors (clfAB), adhesins
      (sdrDE), and capsular polysaccharides (cap8EFGL), resulting in more intact
      biofilm. In addition, in this study we were able to identify the pathways
      involved in the adaptation of S. aureus to the stress of ChT treatment. Further,
      EtOH suppressed the effect of ChT on gene expression when these agents were used
      together at sublethal concentrations. These data show that in the presence of
      sublethal concentrations of tested disinfectants, S. aureus cells trigger
      protective mechanisms and try to cope with them.IMPORTANCE So far, the effect of
      disinfectants is not satisfactorily explained. The presented data will allow a
      better understanding of the mode of disinfectant action with regard to biofilm
      formation and the ability of bacteria to survive the treatment. Such an
      understanding could contribute to the effort to eliminate possible sources of
      bacteria, making disinfectant application as efficient as possible. Biofilm
      formation plays significant role in the spread and pathogenesis of bacterial
      species.

PMID- 29030438
TI  - Role of Wall Shear Stress in Cryptosporidium parvum Oocyst Attachment to
      Environmental Biofilms.
AB  - This study investigated Cryptosporidium parvum oocyst deposition onto biofilms as
      a function of shear stress under laminar or turbulent flow. Annular rotating
      bioreactors were used to grow stabilized stream biofilms at shear stresses
      ranging from 0.038 to 0.46 Pa. These steady-state biofilms were then used to
      assess the impact of hydrodynamic conditions on C. parvum oocyst attachment. C.
      parvum deposition onto biofilms followed a pseudo-second-order model under both
      laminar (after a lag phase) and turbulent flows. The total number of oocysts
      attached to the biofilm at steady state decreased as the hydrodynamic wall shear
      stress increased. The oocyst deposition rate constant increased with shear stress
      but decreased at high shear, suggesting that increasing wall shear stress results
      in faster attachment of Cryptosporidium due to higher mass transport until the
      shear forces exceed a critical limit that prevents oocyst attachment. These data
      show that oocyst attachment in the short and long term are impacted differently
      by shear: higher shear (to a certain limit) may be associated with faster initial
      oocyst attachment, but lower shear is associated with greater numbers of oocysts
      attached at equilibrium.IMPORTANCE This research provides experimental evidence
      to demonstrate that shear stress plays a critical role in protozoan-pathogen
      transport and deposition in environmental waters. The data presented in this work
      expand scientific understanding of Cryptosporidium attachment and fate, which
      will further influence the development of timely and accurate sampling
      strategies, as well as advanced water treatment technologies, to target protozoan
      pathogens in surface waters that serve as municipal drinking water sources.

PMID- 29030439
TI  - Conjugation-mediated horizontal gene transfer of Clostridium perfringens plasmids
      in the chicken gastrointestinal tract results in the formation of new virulent
      strains.
AB  - Clostridium perfringens is a gastrointestinal pathogen capable of causing disease
      in a variety of hosts. Necrotic enteritis in chickens is caused by C. perfringens
      strains that produce the pore-forming toxin NetB, the major virulence factor for
      this disease. Like many other C. perfringens toxins and antibiotic resistance
      genes, NetB is encoded on a conjugative plasmid. Conjugative transfer of the netB
      containing plasmid pJIR3535 has been demonstrated in vitro with a netB null
      mutant. This study has investigated the effect of plasmid transfer on disease
      pathogenesis, with two genetically distinct transconjugants constructed under in
      vitro conditions, within the intestinal tract of chickens. This study also
      demonstrates that plasmid transfer can occur naturally in the host gut
      environment, without the need for antibiotic selective pressure to be applied.
      The demonstration of plasmid transfer within the chicken host may have
      implications for disease progression and pathogenesis of C. perfringens-mediated
      disease. Such horizontal gene transfer events are likely to be common in the
      clostridia and may be a key factor in strain evolution, both within animals and
      in the wider environment.ImportanceClostridium perfringens is a major
      gastrointestinal pathogen of poultry. C. perfringens strains that express the
      NetB pore-forming toxin, which is encoded on a conjugative plasmid, cause
      necrotic enteritis. This study demonstrated that the conjugative transfer of the
      netB containing plasmid to two different non-pathogenic strains converted them
      into disease causing strains with similar disease-causing capability as the donor
      strain. Plasmid transfer of netB and antibiotic resistance was also demonstrated
      to occur within the gastrointestinal tract of chickens, with approximately 14% of
      isolates recovered comprising of three distinct, in vivo derived, transconjugant
      types. The demonstration of in vivo plasmid transfer indicates the potential
      importance of strain plasticity and the contribution of plasmids to strain
      virulence.

PMID- 29030440
TI  - Multiple Roles for Two Efflux Pumps in the Polycyclic Aromatic Hydrocarbon
      Degrading Pseudomonas putida Strain B6-2 (DSM 28064).
AB  - Microbial bioremediation is a promising approach for the removal of polycyclic
      aromatic hydrocarbon (PAH) contaminants. Many degraders of PAHs possess efflux
      pump genes in their genomes; however, their specific roles in the degradation of
      PAHs have not been clearly elucidated. In this study, two efflux pumps, TtgABC
      and SrpABC, were systematically investigated to determine their functions in a
      PAH-degrading Pseudomonas putida strain B6-2 (DSM 28064). The disruption of genes
      ttgABC or srpABC resulted in a defect in organic solvent tolerance. TtgABC was
      found to contribute to antibiotic resistance; SrpABC only contributed to
      antibiotic resistance under an artificial overproduced condition. Moreover, a
      mutant strain without srpABC did not maintain its activity in long-term biphenyl
      (BP) degradation, which correlated with the loss of cell viability. The
      expression of SrpABC was significantly upregulated in the course of BP
      degradation. BP, 2-hydroxybiphenyl, 3-hydroxybiphenyl, and 2,3-dihydroxybiphenyl
      (2,3-DHBP) were revealed to be the inducers of srpABC 2,3-DHBP was verified to be
      a substrate of pump SrpABC; SrpABC can enhance the tolerance to 2,3-DHBP by
      pumping it out. The mutant strain B6-2DeltasrpS prolonged BP degradation with the
      increase of srpABC expression. These results suggest that the pump SrpABC of
      strain B6-2 plays a positive role in BP biodegradation by pumping out metabolized
      toxic substances such as 2,3-DHBP. This study provides insights into the
      versatile physiological functions of the widely distributed efflux pumps in the
      biodegradation of PAHs.IMPORTANCE Polycyclic aromatic hydrocarbons (PAHs) are
      notorious for their recalcitrance to degradation in the environment. A high
      frequency of the occurrence of the efflux pump genes was observed in the genomes
      of effective PAH degraders; however, their specific roles in the degradation of
      PAHs are still obscure. The significance of our study is in the identification of
      the function and mechanism of the efflux pump SrpABC of Pseudomonas putida strain
      B6-2 (DSM 28064) in the biphenyl degradation process. SrpABC is crucial for
      releasing the toxicity caused by intermediates that are unavoidably produced in
      PAH degradation, which enables an understanding of how cells maintain the
      intracellular balance of materials. The findings from this study provide a new
      perspective on PAH recalcitrance and shed light on enhancing PAH degradation by
      genetic engineering.

PMID- 29030441
TI  - Methanogenic Paraffin Biodegradation: Alkylsuccinate Synthase Gene Quantification
      and Dicarboxylic Acid Production.
AB  - Paraffinic n-alkanes (>C17) that are solid at ambient temperature comprise a
      large fraction of many crude oils. The comparatively low water solubility and
      reactivity of these long-chain alkanes can lead to their persistence in the
      environment following fuel spills and pose serious problems for crude oil
      recovery operations by clogging oil production wells. However, the degradation of
      waxy paraffins under the anoxic conditions characterizing contaminated
      groundwater environments and deep subsurface energy reservoirs is poorly
      understood. Here, we assessed the ability of a methanogenic culture enriched from
      freshwater fuel-contaminated aquifer sediments to biodegrade the model paraffin n
      octacosane (C28H58). Compared with that in controls, the consumption of n
      octacosane was coupled to methane production, demonstrating its biodegradation
      under these conditions. Smithella was postulated to be an important C28H58
      degrader in the culture on the basis of its high relative abundance as determined
      by 16S rRNA gene sequencing. An identified assA gene (known to encode the alpha
      subunit of alkylsuccinate synthase) aligned most closely with those from other
      Smithella organisms. Quantitative PCR (qPCR) and reverse transcription qPCR
      assays for assA demonstrated significant increases in the abundance and
      expression of this gene in C28H58-degrading cultures compared with that in
      controls, suggesting n-octacosane activation by fumarate addition. A metabolite
      analysis revealed the presence of several long-chain alpha,omega-dicarboxylic
      acids only in the C28H58-degrading cultures, a novel observation providing clues
      as to how methanogenic consortia access waxy hydrocarbons. The results of this
      study broaden our understanding of how waxy paraffins can be biodegraded in
      anoxic environments with an application toward bioremediation and improved oil
      recovery.IMPORTANCE Understanding the methanogenic biodegradation of different
      classes of hydrocarbons has important applications for effective fuel
      contaminated site remediation and for improved recovery from oil reservoirs.
      Previous studies have clearly demonstrated that short-chain alkanes (<C17) can be
      biodegraded anaerobically, but less is understood regarding the biodegradation of
      longer chain waxy alkanes (>C17) that comprise many fuel mixtures. Using an
      enrichment culture derived from a freshwater fuel-contaminated site, we
      demonstrate that the model waxy alkane n-octacosane can be biodegraded under
      methanogenic conditions by a presumed Smithella phylotype. Compared with that of
      controls, we show an increased abundance and expression of the assA gene, which
      is known to be important for anaerobic n-alkane metabolism. Metabolite analyses
      revealed the presence of a range of alpha,omega-dicarboxylic acids found only in
      n-octacosane-degrading cultures, a novel finding that lends insight as to how
      anaerobic communities may access waxes as growth substrates in anoxic
      environments.

PMID- 29030442
TI  - An A/U-Rich Enhancer Region Is Required for High-Level Protein Secretion through
      the HlyA Type I Secretion System.
AB  - Efficient protein secretion is often a valuable alternative to classic cellular
      expression to obtain homogenous protein samples. Early on, bacterial type I
      secretion systems (T1SS) were employed to allow heterologous secretion of fusion
      proteins. However, this approach was not fully exploited, as many proteins could
      not be secreted at all or only at low levels. Here, we present an engineered
      microbial secretion system which allows the effective production of proteins up
      to a molecular mass of 88 kDa. This system is based on the hemolysin A (HlyA)
      T1SS of the Gram-negative bacterium Escherichia coli, which exports polypeptides
      when fused to a hemolysin secretion signal. We identified an A/U-rich enhancer
      region upstream of hlyA required for effective expression and secretion of
      selected heterologous proteins irrespective of their prokaryotic, viral, or
      eukaryotic origin. We further demonstrate that the ribosomal protein S1 binds to
      the hlyA A/U-rich enhancer region and that this region is involved in the high
      yields of secretion of functional proteins, like maltose-binding protein or human
      interferon alpha-2.IMPORTANCE A 5' untranslated region of the mRNA of substrates
      of type I secretion systems (T1SS) drastically enhanced the secretion efficiency
      of the endogenously secreted protein. The identification of ribosomal protein S1
      as the interaction partner of this 5' untranslated region provides a rationale
      for the enhancement. This strategy furthermore can be transferred to fusion
      proteins allowing a broader, and eventually a more general, application of this
      system for secreting heterologous fusion proteins.

PMID- 29030443
TI  - Novel Metabolic Pathway for N-Methylpyrrolidone Degradation in Alicycliphilus sp.
      Strain BQ1.
AB  - The molecular mechanisms underlying the biodegradation of N-methylpyrrolidone
      (NMP), a widely used industrial solvent that produces skin irritation in humans
      and is teratogenic in rats, are unknown. Alicycliphilus sp. strain BQ1 degrades
      NMP. By studying a transposon-tagged mutant unable to degrade NMP, we identified
      a six-gene cluster (nmpABCDEF) that is transcribed as a polycistronic mRNA and
      encodes enzymes involved in NMP biodegradation. nmpA and the transposon-affected
      gene nmpB encode an N-methylhydantoin amidohydrolase that transforms NMP to gamma
      N-methylaminobutyric acid; this is metabolized by an amino acid oxidase (NMPC),
      either by demethylation to produce gamma-aminobutyric acid (GABA) or by
      deamination to produce succinate semialdehyde (SSA). If GABA is produced, the
      activity of a GABA aminotransferase (GABA-AT), not encoded in the nmp gene
      cluster, is needed to generate SSA. SSA is transformed by a succinate
      semialdehyde dehydrogenase (SSDH) (NMPF) to succinate, which enters the Krebs
      cycle. The abilities to consume NMP and to utilize it for growth were
      complemented in the transposon-tagged mutant by use of the nmpABCD genes.
      Similarly, Escherichia coli MG1655, which has two SSDHs but is unable to grow in
      NMP, acquired these abilities after functional complementation with these genes.
      In wild-type (wt) BQ1 cells growing in NMP, GABA was not detected, but SSA was
      present at double the amount found in cells growing in Luria-Bertani medium (LB),
      suggesting that GABA is not an intermediate in this pathway. Moreover, E. coli
      GABA-AT deletion mutants complemented with nmpABCD genes retained the ability to
      grow in NMP, supporting the possibility that gamma-N-methylaminobutyric acid is
      deaminated to SSA instead of being demethylated to GABA.IMPORTANCEN
      Methylpyrrolidone is a cyclic amide reported to be biodegradable. However, the
      metabolic pathway and enzymatic activities for degrading NMP are unknown. By
      developing molecular biology techniques for Alicycliphilus sp. strain BQ1, an
      environmental bacterium able to grow in NMP, we identified a six-gene cluster
      encoding enzymatic activities involved in NMP degradation. These findings set the
      basis for the study of new enzymatic activities and for the development of
      biotechnological processes with potential applications in bioremediation.

PMID- 29030444
TI  - Aerobic Anoxygenic Photosynthesis Is Commonly Present within the Genus
      Limnohabitans.
AB  - The genus Limnohabitans (Comamonadaceae, Betaproteobacteria) is a common and a
      highly active component of freshwater bacterioplanktonic communities. To date,
      the genus has been considered to contain only heterotrophic species. In this
      study, we detected the photosynthesis genes pufLM and bchY in 28 of 46 strains
      from three Limnohabitans lineages. The pufM sequences obtained are very closely
      related to environmental pufM sequences detected in various freshwater habitats,
      indicating the ubiquity and potential importance of photoheterotrophic
      Limnohabitans in nature. Additionally, we sequenced and analyzed the genomes of 5
      potentially photoheterotrophic Limnohabitans strains, to gain further insights
      into their phototrophic capacity. The structure of the photosynthesis gene
      cluster turned out to be highly conserved within the genus Limnohabitans and also
      among all potentially photosynthetic Betaproteobacteria strains. The expression
      of photosynthetic complexes was detected in a culture of Limnohabitans
      planktonicus II-D5T using spectroscopic and pigment analyses. This was further
      verified by a novel combination of infrared microscopy and fluorescent in situ
      hybridization.IMPORTANCE The data presented document that the capacity to perform
      anoxygenic photosynthesis is common among the members of the genus Limnohabitans,
      indicating that they may have a novel role in freshwater habitats.

PMID- 29030445
TI  - Microhomology-Mediated High-Throughput Gene Inactivation Strategy for the
      Hyperthermophilic Crenarchaeon Sulfolobus islandicus.
AB  - Sulfolobus islandicus is rapidly emerging as a model system for studying the
      biology and evolution within the TACK lineage of the archaeal domain. As the tree
      of life grows, identifying the cellular functions of genes within this lineage
      will have significant impacts on our understanding of the evolution of the last
      archaeal eukaryote common ancestor (LEACA) and the differentiation of archaea
      from eukaryotes during the evolution of the modern-day cell. To increase our
      understanding of this key archaeal organism, we report a novel high-throughput
      method for targeted gene inactivation in S. islandicus through one-step
      microhomology-directed homologous recombination (HR). We validated the efficacy
      of this approach by systematically deleting 21 individual toxin-antitoxin gene
      pairs and its application to delete chromosomal regions as large as 50 kb.
      Sequence analysis of 96 ArgD+ transformants showed that S. islandicus can
      effectively incorporate donor markers as short segments through HR in a
      continuous or discontinuous manner. We determined that the minimal size of
      homology allowing native argD marker replacement was as few as 10 bp, whereas
      argD marker replacement was frequently observed when increasing the size of
      homology to 30 to 50 bp. The microhomology-mediated gene inactivation system
      developed here will greatly facilitate isolation of S. islandicus gene deletion
      strains, making generation of a collection of genome-wide targeted mutants
      feasible and providing a tool to investigate homologous recombination in this
      organism.IMPORTANCE Current procedures for the construction of deletion mutants
      of S. islandicus are still tedious and time-consuming. We developed a novel
      procedure based on microhomology-mediated HR, allowing for rapid and efficient
      removal for genetic regions as large as 50 kb. Our work will greatly facilitate
      functional genomic studies in this promising model organism. Additionally, we
      developed a quantitative genetic assay to measure HR properties in S. islandicus,
      providing evidence that the ability to incorporate short, mismatched donor DNA
      into the genome through HR was probably a common trait for members of the
      Sulfolobus genus that are recombinogenic.

PMID- 29030446
TI  - Use of Comparative Genomics-Based Markers for Discrimination of Host Specificity
      in Fusarium oxysporum.
AB  - The polyphyletic nature of many formae speciales of Fusarium oxysporum prevents
      molecular identification of newly encountered strains based on conserved,
      vertically inherited genes. Alternative molecular detection methods that could
      replace labor- and time-intensive disease assays are therefore highly desired.
      Effectors are functional elements in the pathogen-host interaction and have been
      found to show very limited sequence diversity between strains of the same forma
      specialis, which makes them potential markers for host-specific pathogenicity. We
      therefore compared candidate effector genes extracted from 60 existing and 22
      newly generated genome assemblies, specifically targeting strains affecting
      cucurbit plant species. Based on these candidate effector genes, a total of 18
      PCR primer pairs were designed to discriminate between each of the seven
      Cucurbitaceae-affecting formae speciales When tested on a collection of strains
      encompassing different clonal lineages of these formae speciales, nonpathogenic
      strains, and strains of other formae speciales, they allowed clear recognition of
      the host range of each evaluated strain. Within Fusarium oxysporum f. sp. melonis
      more genetic variability exists than anticipated, resulting in three F. oxysporum
      f. sp. melonis marker patterns that partially overlapped with the cucurbit
      infecting Fusarium oxysporum f. sp. cucumerinum, Fusarium oxysporum f. sp.
      niveum, Fusarium oxysporum f. sp. momordicae, and/or Fusarium oxysporum f. sp.
      lagenariae For F. oxysporum f. sp. niveum, a multiplex TaqMan assay was evaluated
      and was shown to allow quantitative and specific detection of template DNA
      quantities as low as 2.5 pg. These results provide ready-to-use marker sequences
      for the mentioned F. oxysporum pathogens. Additionally, the method can be applied
      to find markers distinguishing other host-specific forms of F.
      oxysporumIMPORTANCE Pathogenic strains of Fusarium oxysporum are differentiated
      into formae speciales based on their host range, which is normally restricted to
      only one or a few plant species. However, horizontal gene transfer between
      strains in the species complex has resulted in a polyphyletic origin of host
      specificity in many of these formae speciales This hinders accurate and rapid
      pathogen detection through molecular methods. In our research, we compared the
      genomes of 88 strains of F. oxysporum with each other, specifically targeting
      virulence-related genes that are typically highly similar within each forma
      specialis Using this approach, we identified marker sequences that allow the
      discrimination of F. oxysporum strains affecting various cucurbit plant species
      through different PCR-based methods.

PMID- 29030447
TI  - Housefly (Musca domestica) and Blow Fly (Protophormia terraenovae) as Vectors of
      Bacteria Carrying Colistin Resistance Genes.
AB  - Flies have the capacity to transfer pathogens between different environments,
      acting as one of the most important vectors of human diseases worldwide. In this
      study, we trapped flies on a university campus and tested them for mobile
      resistance genes against colistin, a last-resort antibiotic in human medicine for
      treating clinical infections caused by multidrug-resistant Gram-negative
      bacteria. Quantitative PCR assays we developed showed that 34.1% of Musca
      domestica (86/252) and 51.1% of Protophormia terraenovae (23/45) isolates were
      positive for the mcr-1 gene, 1.2% of M. domestica (3/252) and 2.2% of P.
      terraenovae (2.2%, 1/45) isolates were positive for mcr-2, and 5.2% of M.
      domestica (13/252) and 44.4% of P. terraenovae (20/45) isolates were positive for
      mcr-3 Overall, 4.8% (9/189) of bacteria isolated from the flies were positive for
      the mcr-1 gene (Escherichia coli: 8.3%, 4/48; Enterobacter cloacae: 12.5%, 1/8;
      Providencia alcalifaciens: 11.8%, 2/17; Providencia stuartii: 4.9%, 2/41), while
      none were positive for mcr-2 and mcr-3 Four mcr-1-positive isolates (two P.
      stuartii and two P. alcalifaciens) from blow flies trapped near a dumpster had a
      MIC for colistin above 4 mg/ml. This study reports mcr-1 carriage in Providencia
      spp. and detection of mcr-2 and mcr-3 after their initial identification in
      Belgium and China, respectively. This study suggests that flies might contribute
      significantly to the dissemination of bacteria, carrying these genes into a large
      variety of ecological niches. Further studies are warranted to explore the roles
      that flies might play in the spread of colistin resistance genes.IMPORTANCE
      Antimicrobial resistance is recognized as one of the most serious global threats
      to human health. An option for treatment of the Gram-negative ESKAPE
      (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae,
      Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species)
      bacteria with multiple drug resistance was the reintroduction of the older
      antibiotic colistin. However, a mobile colistin resistance gene (mcr-1) has
      recently been found to occur widely; very recently, two other colistin resistance
      genes (mcr-2 and mcr-3) have been identified in Belgium and China, respectively.
      In this study, we report the presence of colistin resistance genes in flies. This
      study also reports the carriage of colistin resistance genes in the genus
      Providencia and detection of mcr-2 and mcr-3 after their initial identification.
      This study will stimulate more in-depth studies to fully elucidate the
      transmission mechanisms of the colistin resistance genes and their interaction.

PMID- 29030448
TI  - Prevalence and Antimicrobial Resistance of Enterococci Isolated from Retail Meats
      in the United States, 2002 to 2014.
AB  - Bacteria of the genus Enterococcus are important human pathogens that are
      frequently resistant to a number of clinically important antibiotics. They are
      also used as markers of animal fecal contamination of human foods and are
      employed as sentinel organisms for tracking trends in resistance to
      antimicrobials with Gram-positive activity. As part of the National Antimicrobial
      Resistance Monitoring System (NARMS), we evaluated several retail meat
      commodities for the presence of enterococci from 2002 to 2014, and we found 92.0%
      to be contaminated. The majority of isolates were either Enterococcus faecalis
      (64.0%) or Enterococcus faecium (28.6%), and the antimicrobial resistance of each
      isolate was assessed by broth microdilution. The resistance prevalences for
      several drugs, including erythromycin and gentamicin, were significantly higher
      among poultry isolates, compared to retail beef or pork isolates. None of the
      isolates was resistant to the clinically important human drug vancomycin, only 1
      isolate was resistant to linezolid, and resistance to tigecycline was below 1%.
      In contrast, a majority of both E. faecalis (67.5%) and E. faecium (53.7%)
      isolates were resistant to tetracycline. Overall, the robust NARMS testing system
      employed consistent sampling practices and methods throughout the testing period,
      with the only significant trend in resistance prevalence being decreased E.
      faecium resistance to penicillin. These data provide excellent baseline levels of
      resistance that can be used to measure future changes in resistance prevalence
      that may result from alterations in the use of antimicrobials in food animal
      production.IMPORTANCE Enterococci, including E. faecalis and E. faecium, are
      present in the guts of food-producing animals and are used as a measure of fecal
      contamination of meat. We used the large consistent sampling methods of NARMS to
      assess the prevalence of Enterococcus strains isolated from retail meats, and we
      found over 90% of meats to be contaminated with enterococci. We also assessed the
      resistance of the Enterococcus strains, commonly used as a measure of resistance
      to agents with Gram-positive activity, in foods. Resistance prevalence was over
      25% for some antimicrobials and sample sources but was less than 1% for several
      of the most important therapeutic agents used in human medicine.

PMID- 29030449
TI  - Plantaricyclin A, a Novel Circular Bacteriocin Produced by Lactobacillus
      plantarum NI326: Purification, Characterization, and Heterologous Production.
AB  - Bacteriocins from lactic acid bacteria (LAB) are of increasing interest in recent
      years due to their potential as natural preservatives against food and beverage
      spoilage microorganisms. In a screening study for LAB, we isolated from olives a
      strain, Lactobacillus plantarum NI326, with activity against the beverage
      spoilage bacterium Alicyclobacillus acidoterrestris Genome sequencing of NI326
      enabled the identification of a gene cluster (designated plc) encoding a putative
      circular bacteriocin and proteins involved in its modification, transport, and
      immunity. This novel bacteriocin, named plantaricyclin A (PlcA), was grouped into
      the circular bacteriocin subgroup II due to its high degree of similarity with
      other gassericin A-like bacteriocins. Purification of PlcA from the supernatant
      of Lb. plantarum NI326 resulted in an active peptide with a molecular mass of
      5,570 Da, corresponding to that predicted from the (processed) PlcA amino acid
      sequence. The plc gene cluster was cloned and expressed in Lactococcus lactis
      NZ9000, resulting in the production of an active 5,570-Da bacteriocin in the
      supernatant. PlcA is believed to be produced as a 91-amino-acid precursor with a
      33-amino-acid leader peptide, which is predicted to be removed, followed by
      joining of the N and C termini via a covalent linkage to form the mature 58-amino
      acid circular bacteriocin PlcA. We report the characterization of a circular
      bacteriocin produced by Lb. plantarum The inhibition displayed against A.
      acidoterrestris highlights its potential use as a preservative in food and
      beverages.IMPORTANCE In this work, we describe the purification and
      characterization of an antimicrobial peptide, termed plantaricyclin A (PlcA),
      produced by a Lactobacillus plantarum strain isolated from olives. This peptide
      has a circular structure, and all genes involved in its production,
      circularization, and secretion were identified. PlcA shows antimicrobial activity
      against different strains, including Alicyclobacillus acidoterrestris, a common
      spoilage bacterium, which causes substantial economic losses in the beverage
      industry every year. In this study, we describe a circular antimicrobial peptide,
      PlcA, for a Lactobacillus plantarum strain.

PMID- 29030450
TI  - Effect of concussion and blast exposure on symptoms after military deployment.
AB  - OBJECTIVE: To examine whether blast exposure alone and blast-associated
      concussion result in similar neurologic and mental health symptoms. METHODS: A 14
      item questionnaire was administered to male US Marines on their return from
      deployment in Iraq and/or Afghanistan. RESULTS: A total of 2,612 Marines (median
      age 22 years) completed the survey. Of those, 2,320 (88.9%) reported exposure to
      >=1 blast during their current and/or prior deployments. In addition, 1,022
      (39.1%) reported >=1 concussion during the current deployment, and 731 (28.0%)
      had experienced at least 1 prior lifetime concussion. Marines were more likely to
      have sustained a concussion during the current deployment if they had a history
      of 1 (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2-2.0) or >=1 (OR 2.3,
      95% CI 1.7-3.0) prior concussion. The most common symptoms were trouble sleeping
      (38.4%), irritability (37.9%), tinnitus (33.8%), and headaches (33.3%). Compared
      to those experiencing blast exposure without injury, Marines either experiencing
      a concussion during the current deployment or being moved or injured by a blast
      had an increased risk of postinjury symptoms. CONCLUSIONS: There appears to be a
      continuum of increasing total symptoms from no exposure to blast exposure plus
      both current deployment concussion and past concussion. Concussion had a greater
      influence than blast exposure alone on the presence of postdeployment symptoms. A
      high blast injury score can be used to triage those exposed to explosive blasts
      for evaluation.

PMID- 29030451
TI  - Weighting and standardization of frequencies to determine prevalence of AD
      imaging biomarkers.
AB  - OBJECTIVE: To estimate the prevalence of elevated brain amyloid and reduced
      cortical thickness (as a marker for neurodegeneration) in a defined population.
      METHODS: Mayo Clinic Study of Aging participants underwent MRI to assess a
      composite Alzheimer disease (AD) signature cortical thickness measure and PET to
      assess brain amyloid accumulation. Participants were characterized as having
      elevated amyloid (A+/A-), reduced cortical thickness (N+/N-), and A+N+, A+N-, A
      N+, or A-N-. The prevalence of AD biomarkers was derived by adjusting for
      nonparticipation and standardizing to the Olmsted County, Minnesota, population.
      RESULTS: Among 1,646 participants without dementia (mean age 70.8 years; 53.2%
      men), the prevalence (95% confidence interval) of amyloidosis was 21.1% (19.1%
      23.2%): women, 24.3%; men, 17.5%. The prevalence of reduced cortical thickness
      was 28.9% (26.4%-31.5%): women, 27.9%; men, 30.2%. The prevalence estimates of
      biomarker categories were as follows: A-N-: 61.4%; A+N-: 9.7%; A-N+: 17.4%; and
      A+N+: 11.5%, and varied by sex and by APOE epsilon4 carrier status. In men,
      prevalence estimates were as follows: A-N-: 62.6%; A+N-: 7.3%; A-N+: 19.9%; and
      A+N+: 10.2%. In women, prevalence estimates were as follows: A-N-: 60.4%; A+N-:
      11.7%; A-N+: 15.3%; and A+N+: 12.6%. In epsilon4 carriers, prevalence estimates
      were as follows: A-N-: 54.6%; A+N-: 16.6%; A-N+: 12.4%; and A+N+: 16.4%. In non
      epsilon4 carriers, prevalence estimates were as follows: A-N-: 63.3%; A+N-: 6.9%;
      A-N+: 19.9%; and A+N+: 10.0%. CONCLUSIONS: These prevalence estimates are
      important for understanding age-related trends in amyloid positivity and AD
      signature cortical thickness in the population, and for potentially projecting
      the future burden of biomarkers in elderly persons.

PMID- 29030453
TI  - GABA alterations in pediatric sport concussion.
AB  - OBJECTIVE: To evaluate whether frontal-lobe magnetic resonance spectroscopy
      measures of gamma-aminobutyric acid (GABA) would be altered in a sample of
      adolescents scanned after sport concussion because mild traumatic brain injury is
      often associated with working memory problems. METHODS: Eleven adolescents (age
      14-17 years) who had sustained a first-time sport concussion were studied with
      MRI/magnetic resonance spectroscopy within 23 to 44 days after injury (mean 30.4
      +/- 6.1 days). Age- and sex-matched healthy controls, being seen for sports
      related injuries not involving the head and with no history of concussion, were
      also examined. GABA/creatine + phosphocreatine (Cre) was measured in left-sided
      frontal lobe and central posterior cingulate regions. The frontal voxel was
      positioned to overlap with patient-specific activation on a 1-back working memory
      task. RESULTS: Increased GABA/Cre was shown in the frontal lobe for the concussed
      group. A decreased relationship was observed in the parietal region. High
      correlations between GABA/Cre and task activation were observed for the control
      group in the frontal lobe, a relationship not shown in the concussed
      participants. CONCLUSIONS: GABA/Cre appears increased in a region colocalized
      with working memory task activation after sport concussion. Further work
      extending these results in larger samples and at time points across the injury
      episode will aid in refining the clinical significance of these observations.

PMID- 29030454
TI  - Infliximab for the treatment of CNS sarcoidosis: A multi-institutional series.
AB  - OBJECTIVE: To describe clinical and imaging responses in neurosarcoidosis to
      infliximab, a monoclonal antibody against tumor necrosis factor-alpha. METHODS:
      Investigators at 6 US centers retrospectively identified patients with CNS
      sarcoidosis treated with infliximab, including only patients with definite or
      probable neurosarcoidosis following rigorous exclusion of other causes. RESULTS:
      Of 66 patients with CNS sarcoidosis (27 definite, 39 probable) treated with
      infliximab for a median of 1.5 years, the mean age was 47.5 years at infliximab
      initiation (SD 11.7, range 24-71 years); 56.1% were female; 62.1% were white,
      37.0% African American, and 3% Hispanic. Sarcoidosis was isolated to the CNS in
      19.7%. Using infliximab doses ranging from 3 to 7 mg/kg every 4-8 weeks, MRI
      evidence of a favorable treatment response was observed in 82.1% of patients with
      imaging follow-up (n = 56), with complete remission of active disease in 51.8%
      and partial MRI improvement in 30.1%; MRI worsened in 1 patient (1.8%). There was
      clinical improvement in 77.3% of patients, with complete neurologic recovery in
      28.8%, partial improvement in 48.5%, clinical stability in 18.2%, worsening in
      3%, and 1 lost to follow-up. In 16 patients in remission when infliximab was
      discontinued, the disease recurred in 9 (56%), typically in the same
      neuroanatomic location. CONCLUSIONS: Most patients with CNS sarcoidosis treated
      with infliximab exhibit favorable imaging and clinical treatment responses,
      including some previously refractory to other immunosuppressive treatments.
      CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for
      patients with CNS sarcoidosis infliximab is associated with favorable imaging and
      clinical responses.

PMID- 29030455
TI  - Optimal deep brain stimulation site and target connectivity for chronic cluster
      headache.
AB  - OBJECTIVE: To investigate the mechanism of action of deep brain stimulation for
      refractory chronic cluster headache and the optimal target within the ventral
      tegmental area. METHODS: Seven patients with refractory chronic cluster headache
      underwent high spatial and angular resolution diffusion MRI preoperatively. MRI
      guided and MRI-verified electrode implantation was performed unilaterally in 5
      patients and bilaterally in 2. Volumes of tissue activation were generated around
      active lead contacts with a finite-element model. Twelve months after surgery,
      voxel-based morphometry was used to identify voxels associated with higher
      reduction in headache load. Probabilistic tractography was used to identify the
      brain connectivity of the activation volumes in responders, defined as patients
      with a reduction of >=30% in headache load. RESULTS: There was no surgical
      morbidity. Average follow-up was 34 +/- 14 months. Patients showed reductions of
      76 +/- 33% in headache load, 46 +/- 41% in attack severity, 58 +/- 41% in
      headache frequency, and 51 +/- 46% in attack duration at the last follow-up. Six
      patients responded to treatment. Greatest reduction in headache load was
      associated with activation in an area cantered at 6 mm lateral, 2 mm posterior,
      and 1 mm inferior to the midcommissural point of the third ventricle. Average
      responders' activation volume lay on the trigeminohypothalamic tract, connecting
      the trigeminal system and other brainstem nuclei associated with nociception and
      pain modulation with the hypothalamus, and the prefrontal and mesial temporal
      areas. CONCLUSIONS: We identify the optimal stimulation site and structural
      connectivity of the deep brain stimulation target for cluster headache,
      explicating possible mechanisms of action and disease pathophysiology.

PMID- 29030452
TI  - Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy
      controls.
AB  - OBJECTIVE: To analyze longitudinal levels of CSF biomarkers in drug-naive
      patients with Parkinson disease (PD) and healthy controls (HC), examine the
      extent to which these biomarker changes relate to clinical measures of PD, and
      identify what may influence them. METHODS: CSF alpha-synuclein (alpha-syn), total
      and phosphorylated tau (t- and p-tau), and beta-amyloid 1-42 (Abeta42) were
      measured at baseline and 6 and 12 months in 173 patients with PD and 112 matched
      HC in the international multicenter Parkinson's Progression Marker Initiative.
      Baseline clinical and demographic variables, PD medications, neuroimaging, and
      genetic variables were evaluated as potential predictors of CSF biomarker
      changes. RESULTS: CSF biomarkers were stable over 6 and 12 months, and there was
      a small but significant increase in CSF Abeta42 in both patients with patients
      with PD and HC from baseline to 12 months. The t-tau remained stable. The p-tau
      increased marginally more in patients with PD than in HC. alpha-syn remained
      relatively stable in patients with PD and HC. Ratios of p-tau/t-tau increased,
      while t-tau/Abeta42 decreased over 12 months in patients with PD. CSF biomarker
      changes did not correlate with changes in Movement Disorder Society-sponsored
      revision of the Unified Parkinson's Disease Rating Scale motor scores or dopamine
      imaging. CSF alpha-syn levels at 12 months were lower in patients with PD treated
      with dopamine replacement therapy, especially dopamine agonists. CONCLUSIONS:
      These core CSF biomarkers remained stable over 6 and 12 months in patients with
      early PD and HC. PD medication use may influence CSF alpha-syn. Novel biomarkers
      are needed to better profile progressive neurodegeneration in PD.

PMID- 29030457
TI  - Adding quantitative muscle MRI to the FSHD clinical trial toolbox.
AB  - OBJECTIVE: To add quantitative muscle MRI to the clinical trial toolbox for
      facioscapulohumeral muscular dystrophy (FSHD) by correlating it to clinical
      outcome measures in a large cohort of genetically and clinically well
      characterized patients with FSHD comprising the entire clinical spectrum.
      METHODS: Quantitative MRI scans of leg muscles of 140 patients with FSHD1 and
      FSHD2 were assessed for fatty infiltration and TIRM hyperintensities and were
      correlated to multiple clinical outcome measures. RESULTS: The mean fat fraction
      of the total leg musculature correlated highly with the motor function measure,
      FSHD clinical score, Ricci score, and 6-minute walking test (correlation
      coefficients -0.845, 0.835, 0.791, -0.701, respectively). Fat fraction per muscle
      group correlated well with corresponding muscle strength (correlation
      coefficients up to -0.82). The hamstring muscles, adductor muscles, rectus
      femoris, and gastrocnemius medialis were affected most frequently, also in early
      stage disease and in patients without leg muscle weakness. Muscle involvement was
      asymmetric in 20% of all muscle pairs and fatty infiltration within muscles
      showed a decrease from distal to proximal of 3.9%. TIRM hyperintense areas,
      suggesting inflammation, were found in 3.5% of all muscles, with and without
      fatty infiltration. CONCLUSIONS: We show a strong correlation between
      quantitative muscle MRI and clinical outcome measures. Muscle MRI is able to
      detect muscle pathology before clinical involvement of the leg muscles. This
      indicates that quantitative leg muscle MRI is a promising biomarker that captures
      disease severity and motor functioning and can thus be included in the FSHD trial
      toolbox.

PMID- 29030456
TI  - Association between percent decline in serum total homocysteine and risk of first
      stroke.
AB  - OBJECTIVE: To examine whether a change in serum total homocysteine (tHcy) levels
      is associated with first stroke risk in a post hoc analysis of the China Stroke
      Primary Prevention Trial (CSPPT). METHODS: We analyzed 16,867 participants of the
      CSPPT with tHcy measurements at both baseline and exit visits. The primary
      outcome was first stroke. The secondary outcome was a composite of cardiovascular
      events consisting of cardiovascular death, myocardial infarction, and stroke. The
      percent decline in tHcy was calculated as [(baseline tHcy - exit tHcy)/baseline
      tHcy * 100]. RESULTS: Over the median treatment duration of 4.5 years,
      participants who developed a first stroke had a significantly lower percent
      decline in tHcy (beta = -5.7; 95% confidence interval [CI] -8.8 to -2.6) compared
      to their counterparts. A 20% tHcy decline was associated with a reduction in
      stroke risk of 7% (hazard ratio [HR] 0.93; 95% CI 0.90-0.97). When percent
      decline in tHcy was assessed as tertiles, a significantly lower stroke risk was
      found in those in tertiles 2-3 (HR 0.79; 95% CI 0.64-0.97) compared with
      participants in tertile 1. Similar results were observed for the composite of
      cardiovascular events. The beneficial effect associated with greater tHcy
      reduction was observed across strata for age, sex, treatment group (with vs
      without folic acid), MTHFR C677T genotypes, baseline tHcy and serum folate
      levels, and blood pressure control. CONCLUSIONS: Percent lowering in tHcy was
      significantly associated with a reduction in first stroke risk in Chinese adults
      with hypertension, and if further confirmed, may serve as a useful indicator for
      folic acid treatment efficacy on stroke prevention. CLINICALTRIALSGOV IDENTIFIER:
      NCT00794885.

PMID- 29030461
TI  - Varied terrain.

PMID- 29030458
TI  - A noncanonical function of cGAMP in inflammasome priming and activation.
AB  - Recognition of pathogen-associated molecular patterns and danger-associated
      molecular patterns by host cells is an important step in innate immune
      activation. The DNA sensor cyclic guanosine monophosphate-adenosine monophosphate
      (cGAMP) synthase (cGAS) binds to DNA and produces cGAMP, which in turn binds to
      stimulator of interferon genes (STING) to activate IFN-I. Here we show that cGAMP
      has a noncanonical function in inflammasome activation in human and mouse cells.
      Inflammasome activation requires two signals, both of which are activated by
      cGAMP. cGAMP alone enhances expression of inflammasome components through IFN-I,
      providing the priming signal. Additionally, when combined with a priming signal,
      cGAMP activates the inflammasome through an AIM2, NLRP3, ASC, and caspase-1
      dependent process. These two cGAMP-mediated functions, priming and activation,
      have differential requirements for STING. Temporally, cGAMP induction of IFN-I
      precedes inflammasome activation, which then occurs when IFN-I is waning. In
      mice, cGAS/cGAMP amplify both inflammasome and IFN-I to control murine
      cytomegalovirus. Thus, cGAMP activates the inflammasome in addition to IFN-I, and
      activation of both is needed to control infection by a DNA virus.

PMID- 29030459
TI  - Household triclosan and triclocarban effects on the infant and maternal
      microbiome.
AB  - In 2016, the US Food and Drug Administration banned the use of specific
      microbicides in some household and personal wash products due to concerns that
      these chemicals might induce antibiotic resistance or disrupt human microbial
      communities. Triclosan and triclocarban (referred to as TCs) are the most common
      antimicrobials in household and personal care products, but the extent to which
      TC exposure perturbs microbial communities in humans, particularly during infant
      development, was unknown. We conducted a randomized intervention of TC-containing
      household and personal care products during the first year following birth to
      characterize whether TC exposure from wash products perturbs microbial
      communities in mothers and their infants. Longitudinal survey of the gut
      microbiota using 16S ribosomal RNA amplicon sequencing showed that TC exposure
      from wash products did not induce global reconstruction or loss of microbial
      diversity of either infant or maternal gut microbiotas. Broadly antibiotic
      resistant species from the phylum Proteobacteria, however, were enriched in stool
      samples from mothers in TC households after the introduction of triclosan
      containing toothpaste. When compared by urinary triclosan level, agnostic to
      treatment arm, infants with higher triclosan levels also showed an enrichment of
      Proteobacteria species. Despite the minimal effects of TC exposure from wash
      products on the gut microbial community of infants and adults, detected taxonomic
      differences highlight the need for consumer safety testing of antimicrobial self
      care products on the human microbiome and on antibiotic resistance.

PMID- 29030460
TI  - HMG-CoA Reductase Inhibition Delays DNA Repair and Promotes Senescence After
      Tumor Irradiation.
AB  - Despite significant advances in combinations of radiotherapy and chemotherapy,
      altered fractionation schedules and image-guided radiotherapy, many cancer
      patients fail to benefit from radiation. A prevailing hypothesis is that
      targeting repair of DNA double strand breaks (DSB) can enhance radiation effects
      in the tumor and overcome therapeutic resistance without incurring off-target
      toxicities. Unrepaired DSBs can block cancer cell proliferation, promote cancer
      cell death, and induce cellular senescence. Given the slow progress to date
      translating novel DSB repair inhibitors as radiosensitizers, we have explored
      drug repurposing, a proven route to improving speed, costs, and success rates of
      drug development. In a prior screen where we tracked resolution of ionizing
      radiation-induced foci (IRIF) as a proxy for DSB repair, we had identified
      pitavastatin (Livalo), an HMG-CoA reductase inhibitor commonly used for lipid
      lowering, as a candidate radiosensitizer. Here, we report that pitavastatin and
      other lipophilic statins are potent inhibitors of DSB repair in breast and
      melanoma models both in vitro and in vivo When combined with ionizing radiation,
      pitavastatin increased persistent DSBs, induced senescence, and enhanced acute
      effects of radiation on radioresistant melanoma tumors. shRNA knockdown
      implicated HMG-CoA reductase, farnesyl diphosphate synthase, and protein farnesyl
      transferase in IRIF resolution, DSB repair, and senescence. These data confirm on
      target activity of statins, although via inhibition of protein prenylation rather
      than cholesterol biosynthesis. In light of prior studies demonstrating enhanced
      efficacy of radiotherapy in patients taking statins, this work argues for
      clinical evaluation of lipophilic statins as nontoxic radiosensitizers to enhance
      the benefits of image-guided radiotherapy. Mol Cancer Ther; 17(2); 407-18.
      (c)2017 AACRSee all articles in this MCT Focus section, "Developmental
      Therapeutics in Radiation Oncology."

PMID- 29030462
TI  - Selective ophthalmic artery chemosurgery (SOAC) for retinoblastoma: fluoroscopic
      time and radiation dose parameters. A baseline study.
AB  - OBJECTIVE: To evaluate fluoroscopic time and radiation dose parameters, and
      factors affecting these parameters, during selective ophthalmic artery
      chemosurgery (SOAC) for retinoblastoma. MATERIALS AND METHODS: Retrospective
      review from the prospective database of all patients with retinoblastoma treated
      with SOAC over a 5-year period (September 2009-January 2015) at a single
      institution after receiving institutional review board approval. Patient
      demographics, arterial approach, access device, side of treatment, number of SOAC
      cycles/patient, number of drugs/SOAC, and radiation parameters (outcome
      variables), including the fluoroscopic time, dose-area product (DAP), and total
      radiation dose, were obtained from the database. Generalized linear regression
      was used for univariate and multivariate analysis of the outcome variables.
      RESULTS: In 218 patients (M:F=94:124), 272 eyes were treated by 833 SOAC
      infusions during 792 procedures. Mean age, weight, SOAC cycle/patient, and
      drugs/cycle were 19+/-19.5 months, 11.4+/-6.4 kg, 2.72+/-1.6, and 2.48+/-0.8,
      respectively. Mean fluoroscopic time, DAP, and doses were 10.2+/-8.4 min, 218.7+/
      240.8 cGy.cm2, and 42.3+/-41.4 mGy, respectively. Radiation parameters
      (fluoroscopic time, DAP, and dose) were significantly lower (p<0.001) for the
      ophthalmic artery (OA) approach (7.5+/-5.4; 147.7+/-138.4; 28.5+/-29.4) than with
      middle meningeal artery (13.4+/-5.6; 242+/-138; 51.4+/-27) and balloon-assisted
      infusion in the internal carotid artery (ICA; 17.8+/-11.5; 449.8+/-361; 81.8+/
      63.3). Radiation parameters for microcatheter access (8.6+/-7.1; 193.4+/-181.3;
      42.3+/-37) were significantly lower (p<0.001) than with the ICA (17.8+/-11.5;
      449.8+/-361; 81.8+/-63.3). Radiation parameters for bilateral IA chemotherapy
      (IAC; 16.8+/-11.6; 320.7+/-268.7; 60.8+/-45.6) were significantly higher
      (p<0.001) than for unilateral IAC (8.9+/-6.6; 212.7+/-247; 42+/-41). CONCLUSIONS:
      In SOAC for retinoblastoma, the OA approach, microcatheter access, and unilateral
      treatment were associated with significantly lower radiation parameters. We
      established benchmark radiation parameters for retinoblastoma SOAC in our patient
      cohort.

PMID- 29030463
TI  - Efficacy and safety of the target puncture technique for treatment of
      osteoporotic vertebral compression fractures with intravertebral clefts.
AB  - OBJECTIVE: To compare the efficacy and safety of our target puncture technique
      with the traditional technique during percutaneous kyphoplasty (PKP) for
      osteoporotic vertebral compression fractures (OVCFs) with intravertebral clefts
      (IVCs). METHODS: 104 patients treated with PKP for single OVCFs with IVCs were
      retrospectively reviewed. All patients were divided into three groups: cleft
      filling by the traditional technique (Group A, n=18); interdigitated filling
      (Group B, n=50); and overfilling by the target technique (Group C, n=36).
      Oswestry disability index (ODI) and visual analog scale (VAS) scores and
      radiological evidence of vertebral body height and kyphotic angle, cement
      leakage, and adjacent vertebral fractures were studied before and after surgery
      (immediate, 1 and 2 years). RESULTS: The ODI and VAS scores decreased for all
      patients and no significant difference was found between the three groups after
      treatment. However, 1 and 2 years after surgery a greater increase in ODI and VAS
      scores was observed in Group A compared with the other two groups. The initial
      correction of vertebral body height and kyphotic angle was not significant among
      the three groups. However, loss of correction was greater in Group A. No
      significant difference was found in cement leakage. The incidence of adjacent
      vertebral fractures in Group C was higher than in the other two groups.
      CONCLUSIONS: Different puncture techniques were initially effective for all
      patients with IVCs. However, cement cleft filling by the traditional technique
      was found to have less stability causing higher VAS/ODI scores and greater loss
      of correction. Hence, our target puncture technique was recommended in this
      study.

PMID- 29030464
TI  - Computed tomography interobserver agreement in the assessment of aneurysmal
      subarachnoid hemorrhage and predictors for clinical outcome.
AB  - BACKGROUND: The severity of aneurysmal subarachnoid hemorrhage (SAH) is often
      assessed by the clinical state of the patient on presentation, but radiological
      evaluation of the extent of hemorrhage has rarely been examined in the
      literature. Several CT scan based grading systems exist yet only a few studies
      have investigated interobserver agreement. We evaluated five radiological grading
      systems and assessed their clinical value for early prognostication. METHODOLOGY:
      This was a retrospective study of patients diagnosed with aneurysmal SAH with a
      CT scan performed within 72 hours of symptom onset. Four independent observers,
      blinded to patient outcome, evaluated each scan using the five grading systems. A
      separate assessor determined 6 month outcome from clinical records. The primary
      outcome was interobserver agreement for each grading system using the Fleiss
      kappa statistic. The secondary endpoint was the 6 month modified Rankin Scale
      score, with poor outcome defined as a score of 4-6. RESULTS: 165 patients with a
      mean age of 59 years were assessed. Interobserver agreement for the Fisher,
      modified Fisher, Claassen, Barrow Neurological Institute, and Hijdra grading
      systems were as follows: k=0.53 (moderate), k=0.42 (moderate), k=0.38 (mild),
      k=0.20 (poor), and k=0.66 (good), respectively. The only independent clinical
      risk factor for poor outcome was a World Federation of Neurological Surgeons
      (WFNS) grade of 4 or 5 (adjusted OR 6.55; p<0.05). After adjusting for
      confounders, Fisher grade 4 (adjusted OR 17.84), modified Fisher grade 4
      (adjusted OR 5.65), and Hijdra grade 3 (adjusted OR 3.34) were associated with
      poor outcome. Receiver operator characteristic analysis revealed that the Hijdra
      grading system (area under the curve=0.76) was more predictive of outcome
      compared with the Fisher and modified Fisher systems. A Hijdra cut-off score of
      22 was associated with poor outcome (adjusted OR 5.92). CONCLUSIONS: The Hijdra
      grading system had the best interobserver agreement and was a better independent
      early predictor for 6 month clinical outcome than the other systems. A Hijdra
      score >=22 was associated with poor outcome.

PMID- 29030466
TI  - Modulation of Renal GLUT2 by the Cannabinoid-1 Receptor: Implications for the
      Treatment of Diabetic Nephropathy.
AB  - Altered glucose reabsorption via the facilitative glucose transporter 2 (GLUT2)
      during diabetes may lead to renal proximal tubule cell (RPTC) injury,
      inflammation, and interstitial fibrosis. These pathologies are also triggered by
      activating the cannabinoid-1 receptor (CB1R), which contributes to the
      development of diabetic nephropathy (DN). However, the link between CB1R and
      GLUT2 remains to be determined. Here, we show that chronic peripheral CB1R
      blockade or genetically inactivating CB1Rs in the RPTCs ameliorated diabetes
      induced renal structural and functional changes, kidney inflammation, and
      tubulointerstitial fibrosis in mice. Inhibition of CB1R also downregulated GLUT2
      expression, affected the dynamic translocation of GLUT2 to the brush border
      membrane of RPTCs, and reduced glucose reabsorption. Thus, targeting peripheral
      CB1R or inhibiting GLUT2 dynamics in RPTCs has the potential to treat and
      ameliorate DN. These findings may support the rationale for the clinical testing
      of peripherally restricted CB1R antagonists or the development of novel renal
      specific GLUT2 inhibitors against DN.

PMID- 29030467
TI  - Metabolic Acidosis and Subclinical Metabolic Acidosis in CKD.
AB  - Metabolic acidosis is not uncommon in CKD and is linked with bone
      demineralization, muscle catabolism, and higher risks of CKD progression and
      mortality. Clinical practice guidelines recommend maintaining serum total CO2 at
      >=22 mEq/L to help prevent these complications. Although a definitive trial
      testing whether correcting metabolic acidosis improves clinical outcomes has not
      been conducted, results from small, single-center studies support this notion.
      Furthermore, biologic plausibility supports the notion that a subset of patients
      with CKD have acid-mediated organ injury despite having a normal serum total CO2
      and might benefit from oral alkali before overt acidosis develops. Identifying
      these individuals with subclinical metabolic acidosis is challenging, but recent
      results suggest that urinary acid excretion measurements may be helpful. The dose
      of alkali to provide in this setting is unknown as well. The review discusses
      these topics and the prevalence and risk factors of metabolic acidosis,
      mechanisms of acid-mediated organ injury, results from interventional studies,
      and potential harms of alkali therapy in CKD.

PMID- 29030465
TI  - Cluster Analysis Identifies Distinct Pathogenetic Patterns in C3
      Glomerulopathies/Immune Complex-Mediated Membranoproliferative GN.
AB  - Membranoproliferative GN (MPGN) was recently reclassified as alternative pathway
      complement-mediated C3 glomerulopathy (C3G) and immune complex-mediated
      membranoproliferative GN (IC-MPGN). However, genetic and acquired alternative
      pathway abnormalities are also observed in IC-MPGN. Here, we explored the
      presence of distinct disease entities characterized by specific pathophysiologic
      mechanisms. We performed unsupervised hierarchical clustering, a data-driven
      statistical approach, on histologic, genetic, and clinical data and data
      regarding serum/plasma complement parameters from 173 patients with C3G/IC-MPGN.
      This approach divided patients into four clusters, indicating the existence of
      four different pathogenetic patterns. Specifically, this analysis separated
      patients with fluid-phase complement activation (clusters 1-3) who had low serum
      C3 levels and a high prevalence of genetic and acquired alternative pathway
      abnormalities from patients with solid-phase complement activation (cluster 4)
      who had normal or mildly altered serum C3, late disease onset, and poor renal
      survival. In patients with fluid-phase complement activation, those in clusters 1
      and 2 had massive activation of the alternative pathway, including activation of
      the terminal pathway, and the highest prevalence of subendothelial deposits, but
      those in cluster 2 had additional activation of the classic pathway and the
      highest prevalence of nephrotic syndrome at disease onset. Patients in cluster 3
      had prevalent activation of C3 convertase and highly electron-dense
      intramembranous deposits. In addition, we provide a simple algorithm to assign
      patients with C3G/IC-MPGN to specific clusters. These distinct clusters may
      facilitate clarification of disease etiology, improve risk assessment for ESRD,
      and pave the way for personalized treatment.

PMID- 29030468
TI  - Assessing the reliability of spike-in normalization for analyses of single-cell
      RNA sequencing data.
AB  - By profiling the transcriptomes of individual cells, single-cell RNA sequencing
      provides unparalleled resolution to study cellular heterogeneity. However, this
      comes at the cost of high technical noise, including cell-specific biases in
      capture efficiency and library generation. One strategy for removing these biases
      is to add a constant amount of spike-in RNA to each cell and to scale the
      observed expression values so that the coverage of spike-in transcripts is
      constant across cells. This approach has previously been criticized as its
      accuracy depends on the precise addition of spike-in RNA to each sample. Here, we
      perform mixture experiments using two different sets of spike-in RNA to quantify
      the variance in the amount of spike-in RNA added to each well in a plate-based
      protocol. We also obtain an upper bound on the variance due to differences in
      behavior between the two spike-in sets. We demonstrate that both factors are
      small contributors to the total technical variance and have only minor effects on
      downstream analyses, such as detection of highly variable genes and clustering.
      Our results suggest that scaling normalization using spike-in transcripts is
      reliable enough for routine use in single-cell RNA sequencing data analyses.

PMID- 29030471
TI  - Retraction for Lee et al., "The BCL11A Transcription Factor Directly Activates
      RAG Gene Expression and V(D)J Recombination".

PMID- 29030470
TI  - Single-cell sequencing data reveal widespread recurrence and loss of mutational
      hits in the life histories of tumors.
AB  - Intra-tumor heterogeneity poses substantial challenges for cancer treatment. A
      tumor's composition can be deduced by reconstructing its mutational history.
      Central to current approaches is the infinite sites assumption that every genomic
      position can only mutate once over the lifetime of a tumor. The validity of this
      assumption has never been quantitatively assessed. We developed a rigorous
      statistical framework to test the infinite sites assumption with single-cell
      sequencing data. Our framework accounts for the high noise and contamination
      present in such data. We found strong evidence for the same genomic position
      being mutationally affected multiple times in individual tumors for 11 of 12
      single-cell sequencing data sets from a variety of human cancers. Seven cases
      involved the loss of earlier mutations, five of which occurred at sites
      unaffected by large-scale genomic deletions. Four cases exhibited a parallel
      mutation, potentially indicating convergent evolution at the base pair level. Our
      results refute the general validity of the infinite sites assumption and indicate
      that more complex models are needed to adequately quantify intra-tumor
      heterogeneity for more effective cancer treatment.

PMID- 29030469
TI  - Single-cell gene expression analysis reveals regulators of distinct cell
      subpopulations among developing human neurons.
AB  - The stochastic dynamics and regulatory mechanisms that govern differentiation of
      individual human neural precursor cells (NPC) into mature neurons are currently
      not fully understood. Here, we used single-cell RNA-sequencing (scRNA-seq) of
      developing neurons to dissect/identify NPC subtypes and critical developmental
      stages of alternative lineage specifications. This study comprises an
      unsupervised, high-resolution strategy for identifying cell developmental
      bifurcations, tracking the stochastic transcript kinetics of the subpopulations,
      elucidating regulatory networks, and finding key regulators. Our data revealed
      the bifurcation and developmental tracks of the two NPC subpopulations, and we
      captured an early (24 h) transition phase that leads to alternative neuronal
      specifications. The consequent up-regulation and down-regulation of stage- and
      subpopulation-specific gene groups during the course of maturation revealed
      biological insights with regard to key regulatory transcription factors and
      lincRNAs that control cellular programs in the identified neuronal
      subpopulations.

PMID- 29030472
TI  - Erratum for Salma et al., "Tfe3 and Tfeb Transcriptionally Regulate Peroxisome
      Proliferator-Activated Receptor gamma2 Expression in Adipocytes and Mediate
      Adiponectin and Glucose Levels in Mice".

PMID- 29030473
TI  - Letter by Tsivgoulis et al Regarding Article, "Microbleeds, Cerebral Hemorrhage,
      and Functional Outcome After Stroke Thrombolysis: Individual Patient Data Meta
      Analysis".

PMID- 29030474
TI  - Off-Label Use of Direct Oral Anticoagulants in Intracerebral Hemorrhage Patients
      With Prosthetic Valves.

PMID- 29030475
TI  - Statins for Neuroprotection After Acute Ischemic Stroke: ASSORTed Results But
      More Trials Needed.

PMID- 29030476
TI  - Added Value of Vessel Wall Magnetic Resonance Imaging for Differentiation of
      Nonocclusive Intracranial Vasculopathies.
AB  - BACKGROUND AND PURPOSE: Our goal is to determine the added value of intracranial
      vessel wall magnetic resonance imaging (IVWI) in differentiating nonocclusive
      vasculopathies compared with luminal imaging alone. METHODS: We retrospectively
      reviewed images from patients with both luminal and IVWI to identify cases with
      clinically defined intracranial vasculopathies: atherosclerosis (intracranial
      atherosclerotic disease), reversible cerebral vasoconstriction syndrome, and
      inflammatory vasculopathy. Two neuroradiologists blinded to clinical data
      reviewed the luminal imaging of defined luminal stenoses/irregularities and
      evaluated the pattern of involvement to make a presumed diagnosis with diagnostic
      confidence. Six weeks later, the 2 raters rereviewed the luminal imaging in
      addition to IVWI for the pattern of wall involvement, presence and pattern of
      postcontrast enhancement, and presumed diagnosis and confidence. Analysis was
      performed on per-lesion and per-patient bases. RESULTS: Thirty intracranial
      atherosclerotic disease, 12 inflammatory vasculopathies, and 12 reversible
      cerebral vasoconstriction syndrome patients with 201 lesions (90 intracranial
      atherosclerotic disease, 64 reversible cerebral vasoconstriction syndrome, and 47
      inflammatory vasculopathy lesions) were included. For both per-lesion and per
      patient analyses, there was significant diagnostic accuracy improvement with
      luminal imaging+IVWI when compared with luminal imaging alone (per-lesion: 88.8%
      versus 36.1%; P<0.001 and per-patient: 96.3% versus 43.5%; P<0.001,
      respectively). There was substantial interrater diagnostic agreement for luminal
      imaging+IVWI (kappa=0.72) and only slight agreement for luminal imaging
      (kappa=0.04). Although there was a significant correlation for both luminal and
      IVWI pattern of wall involvement with diagnosis, there was a stronger correlation
      for IVWI finding of lesion eccentricity and intracranial atherosclerotic disease
      diagnosis than for luminal imaging (kappa=0.69 versus 0.18; P<0.001).
      CONCLUSIONS: IVWI can significantly improve the differentiation of nonocclusive
      intracranial vasculopathies when combined with traditional luminal imaging
      modalities.

PMID- 29030477
TI  - Response by Werring and Charidimou to Letter Regarding Article, "Microbleeds,
      Cerebral Hemorrhage, and Functional Outcome After Stroke Thrombolysis: Individual
      Patient Data Meta-Analysis".

PMID- 29030478
TI  - Randomized Controlled Trial of Early Versus Delayed Statin Therapy in Patients
      With Acute Ischemic Stroke: ASSORT Trial (Administration of Statin on Acute
      Ischemic Stroke Patient).
AB  - BACKGROUND AND PURPOSE: Several studies suggested that statins during
      hospitalization were associated with better disability outcomes in patients with
      acute ischemic stroke, but only 1 small randomized trial is available. METHODS:
      We conducted a multicenter, open-label, randomized controlled trial in patients
      with acute ischemic strokes in 11 hospitals in Japan. Patients with acute
      ischemic stroke and dyslipidemia randomly received statins within 24 hours after
      admission in the early group or on the seventh day in the delayed group, in a 1:1
      ratio. Statins were administered for 12 weeks. The primary outcome was patient
      disability assessed by modified Rankin Scale at 90 days. RESULTS: A total of 257
      patients were randomized and analyzed (early 131, delayed 126). At 90 days,
      modified Rankin Scale score distribution did not differ between groups (P=0.68),
      and the adjusted common odds ratio of the early statin group was 0.84 (95%
      confidence interval, 0.53-1.3; P=0.46) compared with the delayed statin group.
      There were 3 deaths at 90 days (2 in the early group, 1 in the delayed group)
      because of malignancy. Ischemic stroke recurred in 9 patients (6.9%) in the early
      group and 5 patients (4.0%) in the delayed group. The safety profile was similar
      between groups. CONCLUSIONS: Our randomized trial involving patients with acute
      ischemic stroke and dyslipidemia did not show any superiority of early statin
      therapy within 24 hours of admission compared with delayed statin therapy 7 days
      after admission to alleviate the degree of disability at 90 days after onset.
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT02549846.

PMID- 29030480
TI  - Intersectin-s interaction with DENND2B facilitates recycling of epidermal growth
      factor receptor.
AB  - Epidermal growth factor (EGF) activates the EGF receptor (EGFR) and stimulates
      its internalization and trafficking to lysosomes for degradation. However, a
      percentage of EGFR undergoes ligand-independent endocytosis and is rapidly
      recycled back to the plasma membrane. Importantly, alterations in EGFR recycling
      are a common hallmark of cancer, and yet, our understanding of the machineries
      controlling the fate of endocytosed EGFR is incomplete. Intersectin-s is a multi
      domain adaptor protein that is required for internalization of EGFR Here, we
      discover that intersectin-s binds DENND2B, a guanine nucleotide exchange factor
      for the exocytic GTPase Rab13, and this interaction promotes recycling of ligand
      free EGFR to the cell surface. Intriguingly, upon EGF treatment, DENND2B is
      phosphorylated by protein kinase D and dissociates from intersectin-s, allowing
      for receptor targeting to degradation. Our study thus reveals a novel mechanism
      controlling the fate of internalized EGFR with important implications for cancer.

PMID- 29030479
TI  - Lipids at membrane contact sites: cell signaling and ion transport.
AB  - Communication between organelles is essential to coordinate cellular functions
      and the cell's response to physiological and pathological stimuli. Organellar
      communication occurs at membrane contact sites (MCSs), where the endoplasmic
      reticulum (ER) membrane is tethered to cellular organelle membranes by specific
      tether proteins and where lipid transfer proteins and cell signaling proteins are
      located. MCSs have many cellular functions and are the sites of lipid and ion
      transfer between organelles and generation of second messengers. This review
      discusses several aspects of MCSs in the context of lipid transfer, formation of
      lipid domains, generation of Ca2+ and cAMP second messengers, and regulation of
      ion transporters by lipids.

PMID- 29030481
TI  - Antisense transcription represses Arabidopsis seed dormancy QTL DOG1 to regulate
      drought tolerance.
AB  - Plants have developed multiple strategies to sense the external environment and
      to adapt growth accordingly. Delay of germination 1 (DOG1) is a major
      quantitative trait locus (QTL) for seed dormancy strength in Arabidopsis thaliana
      that is reported to be expressed exclusively in seeds. DOG1 is extensively
      regulated, with an antisense transcript (asDOG1) suppressing its expression in
      seeds. Here, we show that asDOG1 shows high levels in mature plants where it
      suppresses DOG1 expression under standard growth conditions. Suppression is
      released by shutting down antisense transcription, which is induced by the plant
      hormone abscisic acid (ABA) and drought. Loss of asDOG1 results in constitutive
      high-level DOG1 expression, conferring increased drought tolerance, while
      inactivation of DOG1 causes enhanced drought sensitivity. The unexpected role of
      DOG1 in environmental adaptation of mature plants is separate from its function
      in seed dormancy regulation. The requirement of asDOG1 to respond to ABA and
      drought demonstrates that antisense transcription is important for sensing and
      responding to environmental changes in plants.

PMID- 29030482
TI  - Membrane scission driven by the PROPPIN Atg18.
AB  - Sorting, transport, and autophagic degradation of proteins in endosomes and
      lysosomes, as well as the division of these organelles, depend on scission of
      membrane-bound tubulo-vesicular carriers. How scission occurs is poorly
      understood, but family proteins bind these membranes. Here, we show that the
      yeast PROPPIN Atg18 carries membrane scission activity. Purified Atg18 drives
      tubulation and scission of giant unilamellar vesicles. Upon membrane contact,
      Atg18 folds its unstructured CD loop into an amphipathic alpha-helix that inserts
      into the bilayer. This allows the protein to engage its two lipid binding sites
      for PI3P and PI(3,5)P2 PI(3,5)P2 induces Atg18 oligomerization, which should
      concentrate lipid-inserted alpha-helices in the outer membrane leaflet and drive
      membrane tubulation and scission. The scission activity of Atg18 is compatible
      with its known roles in endo-lysosomal protein trafficking, autophagosome
      biogenesis, and vacuole fission. Key features required for membrane tubulation
      and scission by Atg18 are shared by other PROPPINs, suggesting that membrane
      scission may be a generic function of this protein family.

PMID- 29030483
TI  - RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling
      via histone demethylase KDM1A/LSD1.
AB  - Notch signaling is an evolutionarily conserved signal transduction pathway that
      is essential for metazoan development. Upon ligand binding, the Notch
      intracellular domain (NOTCH ICD) translocates into the nucleus and forms a
      complex with the transcription factor RBPJ (also known as CBF1 or CSL) to
      activate expression of Notch target genes. In the absence of a Notch signal, RBPJ
      acts as a transcriptional repressor. Using a proteomic approach, we identified
      L3MBTL3 (also known as MBT1) as a novel RBPJ interactor. L3MBTL3 competes with
      NOTCH ICD for binding to RBPJ In the absence of NOTCH ICD, RBPJ recruits L3MBTL3
      and the histone demethylase KDM1A (also known as LSD1) to the enhancers of Notch
      target genes, leading to H3K4me2 demethylation and to transcriptional repression.
      Importantly, in vivo analyses of the homologs of RBPJ and L3MBTL3 in Drosophila
      melanogaster and Caenorhabditis elegans demonstrate that the functional link
      between RBPJ and L3MBTL3 is evolutionarily conserved, thus identifying L3MBTL3 as
      a universal modulator of Notch signaling in metazoans.

PMID- 29030484
TI  - Aubergine and piRNAs promote germline stem cell self-renewal by repressing the
      proto-oncogene Cbl.
AB  - PIWI proteins play essential roles in germ cells and stem cell lineages. In
      Drosophila, Piwi is required in somatic niche cells and germline stem cells
      (GSCs) to support GSC self-renewal and differentiation. Whether and how other
      PIWI proteins are involved in GSC biology remains unknown. Here, we show that
      Aubergine (Aub), another PIWI protein, is intrinsically required in GSCs for
      their self-renewal and differentiation. Aub needs to be loaded with piRNAs to
      control GSC self-renewal and acts through direct mRNA regulation. We identify the
      Cbl proto-oncogene, a regulator of mammalian hematopoietic stem cells, as a novel
      GSC differentiation factor. Aub stimulates GSC self-renewal by repressing Cbl
      mRNA translation and does so in part through recruitment of the CCR4-NOT complex.
      This study reveals the role of piRNAs and PIWI proteins in controlling stem cell
      homeostasis via translational repression and highlights piRNAs as major post
      transcriptional regulators in key developmental decisions.

PMID- 29030485
TI  - Crosstalk between PKA and PKG controls pH-dependent host cell egress of
      Toxoplasma gondii.
AB  - Toxoplasma gondii encodes three protein kinase A catalytic (PKAc1-3) and one
      regulatory (PKAr) subunits to integrate cAMP-dependent signals. Here, we show
      that inactive PKAc1 is maintained at the parasite pellicle by interacting with
      acylated PKAr. Either a conditional knockdown of PKAr or the overexpression of
      PKAc1 blocks parasite division. Conversely, down-regulation of PKAc1 or
      stabilisation of a dominant-negative PKAr isoform that does not bind cAMP
      triggers premature parasite egress from infected cells followed by serial
      invasion attempts leading to host cell lysis. This untimely egress depends on
      host cell acidification. A phosphoproteome analysis suggested the interplay
      between cAMP and cGMP signalling as PKAc1 inactivation changes the
      phosphorylation profile of a putative cGMP-phosphodiesterase. Concordantly,
      inhibition of the cGMP-dependent protein kinase G (PKG) blocks egress induced by
      PKAc1 inactivation or environmental acidification, while a cGMP-phosphodiesterase
      inhibitor circumvents egress repression by PKAc1 or pH neutralisation. This
      indicates that pH and PKAc1 act as balancing regulators of cGMP metabolism to
      control egress. These results reveal a crosstalk between PKA and PKG pathways to
      govern egress in T. gondii.

PMID- 29030487
TI  - Macrophage-Specific Expression of IL-37 in Hyperlipidemic Mice Attenuates
      Atherosclerosis.
AB  - Atherosclerosis, the progressive buildup of plaque within arterial blood vessels,
      can lead to fatal downstream events, such as heart attack or stroke. A key event
      contributing to the development of atherosclerosis is the infiltration of
      monocytes and its associated inflammation, as well as the formation of lipid
      laden macrophage foam cells within the vessel wall. IL-37 is recognized as an
      important anti-inflammatory cytokine expressed especially by immune cells. This
      study was undertaken to elucidate the role of macrophage-expressed IL-37 in
      reducing the production and effects of proinflammatory cytokines, preventing foam
      cell formation, and reducing the development of atherosclerosis. Expression of
      human IL-37 was achieved with a macrophage-specific overexpression system, using
      the CD68 promoter in mouse primary bone marrow-derived macrophages via retroviral
      transduction. Macrophage IL-37 expression in vitro resulted in decreased mRNA
      (e.g., IL-1B, IL-6, and IL-12) and secreted protein production (e.g., IL-6, M
      CSF, and ICAM-1) of key inflammatory mediators. IL-37 expression also inhibited
      macrophage proliferation, apoptosis, and transmigration, as well as reduced lipid
      uptake, compared with controls in vitro. The in vivo effects of macrophage
      expressed IL-37 were investigated through bone marrow transplantation of
      transduced hematopoietic stem cells into irradiated atherosclerosis-prone Ldlr-/-
      mice. After 10 wk on a high-fat/high-cholesterol diet, mice with IL-37-expressing
      macrophages showed reduced disease pathogenesis, which was demonstrated by
      significantly less arterial plaque development and systemic inflammation compared
      with control mice. The athero-protective effect of macrophage-expressed IL-37 has
      implications for development of future therapies to treat atherosclerosis, as
      well as other chronic inflammatory diseases.

PMID- 29030486
TI  - Single-cell RNA sequencing reveals developmental heterogeneity among early
      lymphoid progenitors.
AB  - Single-cell RNA sequencing is a powerful technology for assessing heterogeneity
      within defined cell populations. Here, we describe the heterogeneity of a
      B220+CD117intCD19-NK1.1- uncommitted hematopoietic progenitor having combined
      lymphoid and myeloid potential. Phenotypic and functional assays revealed four
      subpopulations within the progenitor with distinct lineage developmental
      potentials. Among them, the Ly6D+SiglecH-CD11c- fraction was lymphoid-restricted
      exhibiting strong B-cell potential, whereas the Ly6D-SiglecH-CD11c- fraction
      showed mixed lympho-myeloid potential. Single-cell RNA sequencing of these
      subsets revealed that the latter population comprised a mixture of cells with
      distinct lymphoid and myeloid transcriptional signatures and identified a
      subgroup as the potential precursor of Ly6D+SiglecH-CD11c- Subsequent functional
      assays confirmed that B220+CD117intCD19-NK1.1- single cells are, with rare
      exceptions, not bipotent for lymphoid and myeloid lineages. A B-cell priming
      gradient was observed within the Ly6D+SiglecH-CD11c- subset and we propose a
      herein newly identified subgroup as the direct precursor of the first B-cell
      committed stage. Therefore, the apparent multipotency of B220+CD117intCD19-NK1.1-
      progenitors results from underlying heterogeneity at the single-cell level and
      highlights the validity of single-cell transcriptomics for resolving cellular
      heterogeneity and developmental relationships among hematopoietic progenitors.

PMID- 29030488
TI  - Long-Lived Innate IL-17-Producing gamma/delta T Cells Modulate Antimicrobial
      Epithelial Host Defense in the Colon.
AB  - Intestinal IL-17-producing cells, including Th17, gamma/delta T, and innate
      lymphoid cells, are differentially distributed along the gastrointestinal tract.
      In this study, we show that the gut IL-17-producing gamma/delta T (gamma/delta
      T17) cells develop before birth and persist in the tissue as long-lived cells
      with minimal turnover. Most colon gamma/delta T17 cells express, together with
      Vgamma4 and CCR6, the scavenger receptor 2 and are mainly restricted to innate
      lymphoid follicles in the colon. Colon gamma/delta T cells in mice that lack
      conventional dendritic cells 2 produced increased amounts of IL-17 with
      concomitant heightened epithelial antimicrobial response, such as the C-type
      lectins Reg3gamma and Reg3beta. In the absence of gamma/delta T cells or after IL
      17 neutralization, this epithelial response was dramatically reduced, underlining
      the protective role of this unique subpopulation of innate gamma/delta T17 cells
      in the colonic mucosa.

PMID- 29030490
TI  - Early sex-dependent differences in response to environmental stress.
AB  - Developmental plasticity enables the appearance of long-term effects in offspring
      caused by exposure to environmental stressors during embryonic and foetal life.
      These long-term effects can be traced to pre- and post-implantation development,
      and in both cases, the effects are usually sex specific. During preimplantation
      development, male and female embryos exhibit an extensive transcriptional
      dimorphism mainly driven by incomplete X chromosome inactivation. These early
      developmental stages are crucial for the establishment of epigenetic marks that
      will be conserved throughout development, making it a particularly susceptible
      period for the appearance of long-term epigenetic-based phenotypes. Later in
      development, gonadal formation generates hormonal differences between the sexes,
      and male and female placentae exhibit different responses to environmental
      stressors. The maternal environment, including hormones and environmental insults
      during pregnancy, contributes to sex-specific placental development that controls
      genetic and epigenetic programming during foetal development, regulating sex
      specific differences, including sex-specific epigenetic responses to
      environmental hazards, leading to long-term effects. This review summarizes
      several human and animal studies examining sex-specific responses to
      environmental stressors during both the periconception period (caused by
      differences in sex chromosome dosage) and placental development (caused by both
      sex chromosomes and hormones). The identification of relevant sex-dependent
      trajectories caused by sex chromosomes and/or sex hormones is essential to define
      diagnostic markers and prevention/intervention protocols.

PMID- 29030489
TI  - Glyoxals as in vivo RNA structural probes of guanine base-pairing.
AB  - Elucidation of the folded structures that RNA forms in vivo is vital to
      understanding its functions. Chemical reagents that modify the Watson-Crick (WC)
      face of unprotected nucleobases are particularly useful in structure elucidation.
      Dimethyl sulfate penetrates cell membranes and informs on RNA base-pairing and
      secondary structure but only modifies the WC face of adenines and cytosines. We
      present glyoxal, methylglyoxal, and phenylglyoxal as potent in vivo reagents that
      target the WC face of guanines as well as cytosines and adenines. Tests on rice
      (Oryza sativa) 5.8S rRNA in vitro read out by reverse transcription and gel
      electrophoresis demonstrate specific modification of almost all guanines in a
      time- and pH-dependent manner. Subsequent in vivo tests on rice, a eukaryote, and
      Bacillus subtilis and Escherichia coli, Gram-positive and Gram-negative bacteria,
      respectively, showed that all three reagents enter living cells without prior
      membrane permeabilization or pH adjustment of the surrounding media and
      specifically modify solvent-exposed guanine, cytosine, and adenine residues.

PMID- 29030491
TI  - Autophagy is activated in the ovarian tissue of polycystic ovary syndrome.
AB  - The importance of autophagy in polycystic ovary syndrome (PCOS)-related metabolic
      disorders is increasingly being recognized, but few studies have investigated the
      role of autophagy in PCOS. Here, transmission electron microscopy demonstrated
      that autophagy was enhanced in the ovarian tissue from both humans and rats with
      PCOS. Consistent with this, ovarian granulosa cells from PCOS rats showed
      increases in the autophagy marker protein light chain 3B (LC3B), whereas levels
      of the autophagy substrate SQSTM1/p62 were decreased. In addition, the ratio of
      LC3-II/LC3-I was markedly elevated in human PCOS ovarian tissue compared with
      normal ovarian tissue. Real-time PCR arrays indicated that 7 and 34 autophagy
      related genes were down- and up-regulated in human PCOS , Signal-Net, and
      regression analysis suggested that there are a wide range of interactions among
      these 41 genes, and a potential network based on EGFR, ERBB2, FOXO1, MAPK1,
      NFKB1, IGF1,TP53 and MAPK9 may be responsible for autophagy activation in PCOS.
      Systematic functional analysis of 41 differential autophagy-related genes
      indicated that these genes are highly involved in specific cellular processes
      such as response to stress and stimulus, and are linked to four significant
      pathways, including the insulin, ERBB, mTOR signaling pathways and protein
      processing in the endoplasmic reticulum. This study provides evidence for a
      potential role of autophagy disorders in PCOS in which autophagy may be an
      important molecular event in the pathogenesis of PCOS.

PMID- 29030492
TI  - Comparative analysis of activins A and B in the adult mouse epididymis and vas
      deferens.
AB  - Activin A regulates testicular and epididymal development, but the role of
      activin B in the epididymis and vas deferens is unknown. Mouse models with
      reduced activin A (Inhba+/- and InhbaBK/+), or its complete absence (InhbaBK/BK),
      were investigated to identify specific roles of activins in the male reproductive
      tract. In 8-week-old Inhba+/- mice, serum activin A decreased by 70%, with a 50%
      reduction of gene expression and protein in the testis, epididymis and vas
      deferens. Activin B and the activin-binding protein, follistatin, were similar to
      wild-type. Testis weights were slightly reduced in Inhba+/- mice, but the
      epididymis and vas deferens were normal, while the mice were fertile. Activin A
      was decreased by 70% in the serum, testis, epididymis and vas deferens of
      InhbaBK/+ mice and was undetectable in InhbaBK/BK mice, but activin B and
      follistatin levels were similar to wild-type. In 6-week-old InhbaBK/BK mice,
      testis weights were 60% lower and epididymal weights were 50% lower than in
      either InhbaBK/+ or wild-type mice. The cauda epididymal epithelium showed
      infoldings and less intra-luminal sperm, similar to 3.5-week-old wild-type mice,
      but at 8 weeks, no structural differences in the testis or epididymis were noted
      between InhbaBK/BK and wild-type mice. Thus, Inhbb can compensate for Inhba in
      regulating epididymal morphology, although testis and epididymal maturation is
      delayed in mice lacking Inhba Crucially, reduction or absence of activin A, at
      least in the presence of normal activin B levels, does not lead to major defects
      in the adult epididymis or vas deferens.

PMID- 29030493
TI  - Intrinsic aerobic capacity governs the associations between gut microbiota
      composition and fat metabolism age-dependently in rat siblings.
AB  - Host genetic factors affecting the gut microbiome play an important role in
      obesity, yet limited attention has been paid on the host genetic factors linked
      to physical fitness in modifying the microbiome. This study determined whether
      sibling-matched pairs of rats selectively bred for high (HCR) and low (LCR)
      aerobic capacity differ in their microbiome age-dependently and which taxa
      associate with differential in metabolism. Several taxa in young adult rats
      (hereafter young) linked to inherited aerobic capacity, while in older adult
      (hereafter old) rats most of the differences between the lines associated with
      body weight. Despite the absence of weight differential between LCR and HCR when
      young, the LCR microbiome contained more Actinobacteria, Veillonellaceae,
      Coriobacteriaceae, Phascolarctobacterium, and Ruminococcus; taxa previously
      linked to obesity. This raises the question whether the microbiome contributes to
      the later development of obesity in LCR. Age-related differences were detected in
      almost all taxa in both rat lines. The young HCR measured higher for serum
      glycerol and free fatty-acids and lower for cholesterol, HDL, LDL, and
      triglycerides than LCR. The old HCR differed from the old LCR by lower LDL.
      Several metabolites, including LDL, are associated age and genetic background
      dependently with the microbiome, which might explain the metabolic differences
      between the lines. While old lines did not differ in visceral adipose tissue gene
      expression, the young HCR expressed more inflammatory genes than LCR, and several
      taxa including Proteobacteria associated with these genes. In conclusion,
      intrinsic aerobic capacity governs the microbiome, which may influence body
      weight, metabolism, and gene expression.

PMID- 29030494
TI  - Reassurance for many healthy women considering HRT.

PMID- 29030495
TI  - Intracavitary ultrasound (ICARUS): a neuroendoscopic adaptation of intravascular
      ultrasound for intracerebral hemorrhage evacuation.
AB  - Neurosurgeons performing intracerebral hemorrhage evacuation procedures have
      limited options for monitoring hematoma evacuation and assessing residual
      hematoma burden intraoperatively. Here, we report the successful neuroendoscopic
      adaptation of intravascular ultrasound, referred to here as intracavitary
      ultrasound (ICARUS), in two patients. Pre-evacuation ICARUS demonstrated dense
      hematomas in both patients. Post-evacuation ICARUS in patient 1 demonstrated
      significant reduction in clot burden and two focal hyperechoic regions consistent
      with pockets of hematoma not previously seen with the endoscope or burr hole
      ultrasound. These areas were directly targeted and resected with the endoscope
      and suction device. Post-evacuation ICARUS in patient 2 showed significant
      reduction of hematoma volume without indication of residual blood. ICARUS
      findings were confirmed on intraoperative DynaCT and postoperative CT 24 hours
      later. ICARUS is feasibly performed in a hematoma cavity both before and after
      hematoma aspiration. ICARUS may provide additional information to the operating
      surgeon and assist in maximizing hematoma removal.

PMID- 29030496
TI  - Ruptured aneurysm of the artery of Adamkiewicz: is conservative management the
      standard of treatment in the current era?
AB  - Spinal aneurysms are rare lesions, and their natural history is not well known.
      In particular, aneurysms arising from the artery of Adamkiewicz (AA) are an
      extremely rare phenomenon, and given the lack of solid evidence its management
      remains unclear. We present the case of a 54-year-old woman with spinal
      subarachnoid hemorrhage. A spinal angiogram demonstrated a fusiform aneurysm
      arising from the AA. Based on the location, the absence of evident collateral
      circulation to the anterior spinal artery, and the available literature
      supporting spontaneous thrombosis, we opted for conservative management. Fifteen
      days after the diagnosis, a spinal angiogram demonstrated complete occlusion of
      the aneurysm with no visualization of the AA. At 10-month follow-up, the patient
      was able to walk without assistance. Management should be done on a case-by-case
      basis with the goal of preserving spinal cord perfusion. Similar to previous
      articles, our report reinforces conservative management as a valid strategy.

PMID- 29030497
TI  - Flanking the fenestration: circumferential limb-to-limb stent-assisted coiling of
      a basilar artery fenestration aneurysm.
AB  - A man aged 61 years with a history of a ruptured basilar fenestration aneurysm
      underwent unassisted coiling in 1997 and repeat intervention for a recurrence at
      the aneurysm mouth in 2011. At repeat intervention, the decision was made to
      intentionally leave some filling at the base to preserve the parent vessels.
      Stent-assisted coil embolization, although technically feasible, was not pursued
      given the relative risks of the procedure. In 2017, the patient returned for
      repeat surveillance and further coil compaction was found at the aneurysm base.
      With the advent of more compliant woven stents deliverable through 0.017
      microcatheters, stent-assisted coiling was possible. This case demonstrates
      hereto unseen agility afforded by novel low-profile stents allowing a
      circumferential approach to a basilar artery fenestration aneurysm and resultant
      limb-to-limb stent-assisted coiling. Techniques described here may be extended to
      more common anatomic variants that require stent-assisted coiling.

PMID- 29030498
TI  - Late recanalization of basilar artery occlusion in a previously healthy 17-month
      old child.
AB  - Endovascular treatment of acute ischemic stroke in children is increasingly being
      reported, although the time window for intervention is unclear. We describe a
      previously healthy 17-month-old child who presented with vertebral artery
      thrombosis and cerebellar stroke requiring posterior fossa decompression. She
      later progressed to basilar artery thrombosis treated with mechanical
      thrombectomy 50 hours after clinical decline. At 3 month follow-up, the patient
      had a modified Rankin Scale score of 0.

PMID- 29030499
TI  - Unexpected early radiographic findings associated with a ruptured blister-like
      carotid wall aneurysm.
AB  - A 33-year-old man presented with aneurysmal subarachnoid hemorrhage from a
      ruptured, blister-type sidewall internal carotid artery (ICA) aneurysm. Balloon
      assisted coiling was performed with residual neck. He subsequently developed
      severe vasospasm requiring intra-arterial therapies on multiple occasions, during
      which it was noted that despite widespread vasospasm, a focal segment of the ICA
      at the site of the aneurysm showed no significant spasm, suggesting underlying
      vessel abnormality. He was discharged without deficit and scheduled for flow
      diversion given concern over this potentially pathologic segment of vessel. At
      time of scheduled flow diversion 6 weeks later, a de novo unstable-appearing 6 mm
      stalk-like pseudoaneurysm was identified in this segment. Both aneurysms and the
      diseased vessel were successfully treated with Pipeline stenting, with excellent
      clinical and angiographic result. This case highlights the need for close
      angiographic follow-up when there is a heterogeneous vasospastic response in
      arterial segments adjacent to a ruptured aneurysm.

PMID- 29030500
TI  - Prolapsed antrochoanal polyp: an unusual cause of acute adult respiratory
      distress.
AB  - Here we describe an adult male who presented with acute dyspnoea and airway
      occlusion. Nasoendoscopy revealed a large antrochoanal polyp extending from his
      maxillary sinus to the level of the epiglottis. The patient underwent a
      successful semi-emergency polypectomy following initial stabilisation with
      medication.

PMID- 29030501
TI  - Enzymatic synthesis of core 2 O-glycans governs the tissue-trafficking potential
      of memory CD8+ T cells.
AB  - Trafficking of memory CD8+ T cells out of the circulation is essential to provide
      protective immunity against intracellular pathogens in nonlymphoid tissues.
      However, the molecular mechanisms that dictate the trafficking potential of
      diverse memory CD8+ T cell populations are not completely defined. We show that
      after infection or inflammatory challenge, central memory (TCM) CD8+ T cells
      rapidly traffic into nonlymphoid tissues, whereas most effector memory cells
      remain in the circulation. Furthermore, we demonstrate that cellular migration of
      memory CD8+ T cells into nonlymphoid tissues is driven by interleukin-15 (IL-15)
      stimulated enzymatic synthesis of core 2 O-glycans, which generates functional
      ligands for E- and P-selectins. Given that IL-15-stimulated expression of
      glycosyltransferase enzymes is largely a feature of TCM CD8+ T cells, this allows
      TCM to selectively migrate out of the circulation and into nonlymphoid tissues.
      Collectively, our data indicate that entry of memory CD8+ T cells into inflamed,
      nonlymphoid tissues is primarily restricted to TCM cells that have the capacity
      to synthesize core 2 O-glycans.

PMID- 29030502
TI  - Injury talk: spontaneous parent-child conversations in the aftermath of a
      potentially traumatic event.
AB  - BACKGROUND: While talking about traumatic experiences is considered central to
      psychological recovery, little is known about how these conversations occur in
      daily life. OBJECTIVE: We investigated spontaneous injury talk among parents and
      children in the aftermath of a child's hospitalisation due to physical trauma,
      and its relationship with children's socioemotional functioning. METHODS: In a
      prospective naturalistic observation study, we audio-sampled the daily life of 71
      families with the Electronically Activated Recorder after their child (3-16 years
      old) was discharged from hospital. We collected close to 20 000 snippets of audio
      information, which were double-coded for conversation characteristics, and
      measured children's socioemotional functioning with the Strengths and
      Difficulties Questionnaire (SDQ) at 6 weeks and 3 months postinjury. FINDINGS:
      The children were involved in injury talk for, on average, 46 min/day, 9 min of
      which referred to emotions. Children had significantly more injury conversations
      with their mothers than with their fathers. The tone of injury conversations was
      significantly more positive than that of non-injury conversations. More direct
      injury talk was associated with fewer problems on the emotion subscale of the SDQ
      at 3 months. Other associations between aspects of injury talk and children's
      socioemotional functioning were mostly non-significant, although they appeared to
      be stronger at 3 months than at 6 weeks. CONCLUSIONS: Families spontaneously
      talked about the injury and associated issues for about the same amount of time
      per day as a therapist might within a session (a 'therapy hour'). CLINICAL
      IMPLICATIONS: Making full use of naturally occurring injury talk may be a
      valuable direction for parent and family-focused postinjury interventions.
      However, the study design prevents causal inference, and further exploration is
      warranted.

PMID- 29030503
TI  - A qualitative study of a blended therapy using problem solving therapy with a
      customised smartphone app in men who present to hospital with intentional self
      harm.
AB  - BACKGROUND: Blended therapy describes the use of computerised therapy combined
      with face-to-face therapy to extend the depth, range and nature of the face-to
      face therapy. We wanted to develop a treatment manual for a randomised trial of
      blended therapy combining face-to-face problem solving and a smartphone app in
      men who present to hospital with self-harm. OBJECTIVE: To develop a treatment
      manual and to describe the experience of receiving and delivering a blended
      therapy. METHODS: After completion of the blended therapy, semistructured
      qualitative interviews were conducted with participants to describe their
      experience of the treatment. Two independent coders analysed the material using a
      thematic, grounded theory approach. FINDINGS: Seven men were enrolled in the
      study, and six completed the qualitative interviews. The two main themes
      identified were of trust and connection. Participants attended 85% of their
      appointments. CONCLUSIONS: In the treatment manual, we emphasised the themes of
      trust and connection by allowing time to discuss the app in the face-to-face to
      sessions, ensuring that therapists are familiar with the app and know how to
      respond to technical queries. Identification of trust and connection generates
      novel questions about the importance of the therapeutic alliance with technology
      rather than with people. CLINICAL IMPLICATIONS: Clinicians and app developers
      need to pay attention to the therapeutic relationship with technology as trust
      and good communication can be easily damaged, resulting in disengagement with the
      app. Blended therapy may result in increased adherence to face-to-face sessions.
      TRIAL REGISTRATION NUMBER: NCT02718248.

PMID- 29030504
TI  - SAC C VS disease surveillance, June 2017.
AB  - Shortened limbs in pedigree Aberdeen Angus calvesSpinal listeriosis in a suckled
      calfTickborne fever in lambsAeromonas hydrophila pleuropneumonia in finishing
      pigsThese are among matters discussed in the disease surveillance report for June
      2017 from SAC Consulting: Veterinary Services (SAC C VS).

PMID- 29030505
TI  - Infectious bovine rhinotracheitis in Scotland.
AB  - A cattle dashboard has recently been developed to share surveillance information
      gathered from submissions to the Great Britain veterinary diagnostic network.
      Data relating to Scotland come from the SAC C VS. This article, by Tim Geraghty,
      relates to cases of infectious bovine rhinotracheitis in Scotland, as summarised
      on the APHA Cattle Dashboard.

PMID- 29030506
TI  - Tackling brachycephaly head on.

PMID- 29030509
TI  - Aggressive or threatening behaviour a 'weekly occurrence' for vets in practice.

PMID- 29030508
TI  - Raw feeding of pets: safe and nutritious - or reckless and irresponsible?

PMID- 29030510
TI  - Demand for pets creates online pet sales epidemic.

PMID- 29030511
TI  - Meet El Rey Magnum.

PMID- 29030512
TI  - Gove announces plans to ban sale of ivory.

PMID- 29030513
TI  - Clinicians' attitudes to pain and the use of analgesia in cattle.

PMID- 29030514
TI  - Labelling of meat from non-stun slaughtered animals.

PMID- 29030515
TI  - Benchmarking antimicrobial use.

PMID- 29030516
TI  - Labelling of meat from non-stun slaughtered animals.

PMID- 29030522
TI  - Understanding and managing arthritis.
AB  - No-one is more surprised than Hannah Capon at her decision to leave clinical
      practice to help arthritic dogs. This is how it happened.

PMID- 29030517
TI  - Michael Alan Wright.
AB  - Michael Wright was a respected vet who had great pride in his profession.

PMID- 29030523
TI  - Rosie's diary.
AB  - Every month, Vet Record Careers checks in with fourth-year vet student Rosie
      Perrett.

PMID- 29030524
TI  - TodaysBaby Quality Improvement: Safe Sleep Teaching and Role Modeling in 8 US
      Maternity Units.
AB  - BACKGROUND AND OBJECTIVES: Nursing education and role modeling can increase
      adherence to safe sleep practices. Eight US hospital maternity units with
      variable baseline approaches to education participated in a national multicenter
      nursing quality improvement (QI) intervention to promote safe sleep practices.
      The goals at participating maternity units were to (1) increase the rate of
      mothers who reported receiving safe sleep information from nurses to >=90% and
      (2) increase the rates of infants observed sleeping supine in a safe environment
      to >=90%. METHODS: A safe sleep QI toolkit, designed for and provided to all
      sites, included an educational curriculum and tools to use for staff and parent
      education. Local teams implemented safe sleep education using the tools as plan
      do-study-act cycles. After each cycle, audits assessing maternal report of
      nursing education on safe sleep and inpatient infant sleep position and
      environment were performed. RESULTS: The QI interventions lasted a median of 160
      days (range, 101-273). Mothers reported receiving information on 4 primary safe
      sleep topics 72% to 95% of the time (a 24%-57% increase over the baseline).
      Additionally, 93% of infants were observed in a supine sleep position, and 88% of
      infants were observed in a safe sleep environment (a 24% and 33% increase over
      baseline, respectively). These rates were sustained up to 12 months later.
      CONCLUSIONS: Implementation of a multisite QI intervention for safe sleep
      parenting education and role modeling led to increased knowledge of and
      compliance with safe sleep practices during postpartum hospitalization.

PMID- 29030526
TI  - Guidelines for Risk-Based Changeover of Biopharma Multi-Product Facilities.
AB  - In multi-product biopharma facilities, the protection from product contamination
      due to the manufacture of multiple products simultaneously is paramount to assure
      product quality. To that end, the use of traditional changeover methods
      (elastomer change-out, full sampling, etc.) have been widely used within the
      industry and have been accepted by regulatory agencies. However, with the
      endorsement of Quality Risk Management (1), the use of risk-based approaches may
      be applied to assess and continuously improve established changeover processes.
      All processes, including changeover, can be improved with investment
      (money/resources), parallel activities, equipment design improvements, and
      standardization. However, processes can also be improved by eliminating waste.
      For product changeover, waste is any activity not needed for the new process or
      that does not provide added assurance of the quality of the subsequent product.
      The application of a risk-based approach to changeover aligns with the principles
      of Quality Risk Management. Through the use of risk assessments, the appropriate
      changeover controls can be identified and controlled to assure product quality is
      maintained. Likewise, the use of risk assessments and risk-based approaches may
      be used to improve operational efficiency, reduce waste, and permit concurrent
      manufacturing of products.

PMID- 29030527
TI  - Holistic Considerations in Optimizing a Sterile Product Package to Ensure
      Container Closure Integrity.
AB  - A new major chapter dealing with container closure integrity was released by the
      United States Pharmacopeial Convention. Chapter <1207> provides a significant
      amount of education and guidance concerning test methodologies to prove that a
      system is integral and safe for use. The test method used is only one of the
      major considerations in approaching the challenge of proving an integral system.
      This paper takes a holistic review of all the major considerations needed in
      qualifying a new vial system for container closure integrity. There is
      substantial interplay among many aspects in the process of sealing a vial. This
      review helps to define major risks that need to be considered and mitigated and
      reinforces the need to understand the maximum allowable leakage limit that is
      acceptable for a specific drug application. A typical risk-based approach
      considers materials, test methods, process, people, environment, and equipment.
      Each of these aspects is considered in some detail along with a recommended
      process flow for building a best practice, science-based approach. This approach
      will inform decision making for evaluating the correct combination of components
      and assuring they are assembled and tested in an appropriate manner. This work,
      once completed, can be the basis for a vial system platform or specific drug
      application qualification.LAY ABSTRACT: Container closure integrity is a
      fundamental requirement of every sterile drug package. With recent upgrading of
      compendia standards and guidance around this issue, there is an opportunity to
      better define a best practice approach to a complicated subject. It is important
      to recognize that there is substantial interplay among the components of the
      system, the process of assembly, and the test methods that are used. This paper
      takes a holistic approach to discussing these issues and identifying the risks
      that must be considered in assuring an integral container over the shelf life of
      a drug product.

PMID- 29030525
TI  - Neurodevelopment at Age 10 Years of Children Born <28 Weeks With Fetal Growth
      Restriction.
AB  - OBJECTIVES: We sought to evaluate the relationships between fetal growth
      restriction (FGR) (both severe and less severe) and assessments of cognitive,
      academic, and adaptive behavior brain function at age 10 years. METHODS: At age
      10 years, the Extremely Low Gestational Age Newborns Cohort Study assessed the
      cognitive function, academic achievement, social-communicative function,
      psychiatric symptoms, and overall quality of life of 889 children born before 28
      weeks' gestation. A pediatric epileptologist also interviewed parents as part of
      a seizure evaluation. The 52 children whose birth weight z scores were <-2 were
      classified as having severe FGR, and the 113 whose birth weight z scores were
      between -2 and -1 were considered to have less severe FGR. RESULTS: The more
      severe the growth restriction in utero, the lower the level of function on
      multiple cognitive and academic achievement assessments performed at age 10
      years. Growth-restricted children were also more likely than their extremely
      preterm peers to have social awareness impairments, autistic mannerisms, autism
      spectrum diagnoses, difficulty with semantics and speech coherence, and
      diminished social and psychosocial functioning. They also more frequently had
      phobias, obsessions, and compulsions (according to teacher, but not parent,
      report). CONCLUSIONS: Among children born extremely preterm, those with severe
      FGR appear to be at increased risk of multiple cognitive and behavioral
      dysfunctions at age 10 years, raising the possibility that whatever adversely
      affected their intrauterine growth also adversely affected multiple domains of
      cognitive and neurobehavioral development.

PMID- 29030528
TI  - Real-Time PCR Detection of Burkholderia cepacia in Pharmaceutical Products
      Contaminated with Low Levels of Bacterial Contamination.
AB  - A real-time polymerase chain reaction (RT-PCR) assay was developed to detect
      Burkholderia cepacia in pharmaceutical products contaminated with low levels of
      bacteria. Different pharmaceutical suspensions were artificially contaminated
      with B. cepacia, Escherichia coli, Staphylococcus aureus, and Bacillus megaterium
      After a 24 h incubation in trypticase soy broth with Tween 20, samples were
      streaked on mannitol salt, phenyl ethyl alcohol, eosin methylene blue, MacConkey,
      and pseudomonas isolation agar. Microbial DNA was extracted from each sample by
      using a Tris-EDTA, proteinase K, Tween 20 buffer. Regular PCR targeting the 1.5
      kilobases 16S rRNA eubacterial gene and cloning showed the predominant DNA in the
      extracted mix belonged to E. coli Selective media isolation of bacterial
      contamination showed B. cepacia only detected on pseudomonas isolation while
      eosin methylene blue and MacConkey detected only E. coli RT-PCR using primers
      PSL1 and PSR1 amplified a 209 bp 16S rRNA fragment using a Roche LightCycler
      96(r) system with SYBR green I, a common double-stranded binding dye. The cycle
      at which fluorescence from amplification exceeds the background fluorescence was
      referred to as quantification cycle. All samples were found to be positive by
      standard microbiological testing and RT-PCR. B. cepacia was detected within 30 h
      in all contaminated samples using RT-PCR. Based upon standard curve analysis of
      B. cepacia DNA, the minimum DNA concentration that could be detected was 10 fg/uL
      with a correlation value of 0.98. RT-PCR detection of B. cepacia allowed faster
      quality control analysis, corrective actions, and process optimization.LAY
      ABSTRACT: A real-time polymerase chain reaction (RT-PCR) assay was developed to
      detect Burkholderia cepacia in pharmaceutical products contaminated with low
      levels of bacteria. B. cepacia is the number one reason for microbial
      contamination recalls of non-sterile drug products in the USA. RT-PCR using
      primers PSL1 and PSR1 amplified a 209 bp 16S rRNA fragment using a Roche
      LightCycler 96(r) system with SYBR green I, a common double-stranded binding dye.
      All samples were found to be positive by standard microbiological testing and RT
      PCR. B. cepacia was detected within 30 h in all contaminated samples using RT
      PCR. RT-PCR detection of B. cepacia allowed faster quality control analysis,
      corrective actions, and process optimization.

PMID- 29030529
TI  - Microbiological Test Data-Assuring Data Integrity.
AB  - Marketed drugs and devices possess specifications including critical
      microbiological quality attributes purposed to assure efficacy and patient
      safety. These attributes are legislated requirements intended to protect the
      recipient patient. Sampling, microbiological testing, interpretation of data for
      final products, raw materials, and intermediates all contribute to a cohesive
      assessment in the assurance of finished product quality. Traditional culture
      based microbiological methods possess inherent and unavoidable variability,
      recognized by the compendia and which might lead to erroneous conclusion
      pertaining to product quality. Such variability has been associated and
      intrinsically linked with data integrity issues; manufacturers have subsequently
      been encouraged by regulatory authorities to introduce multiple microbiologists
      or checks to prevent such issues. Understanding microbiological variability is
      essential such that genuine data integrity issues are identified. Furthermore, a
      range of meaningful preventative strategies are feasible beyond increasing the
      capacity of the quality control microbiological laboratory. This short review
      describes the legislative requirements, inherent microbiological variability, and
      realistic actions and activities that genuinely assure patient safety.LAY
      ABSTRACT: Marketed drugs and devices possess specifications including critical
      microbiological quality attributes purposed to assure efficacy and patient
      safety. These attributes are legislated requirements intended to protect the
      recipient patient. Sampling, microbiological testing, interpretation of data for
      final products, raw materials, and intermediates all contribute to a cohesive
      assessment in the assurance of finished product quality. Traditional culture
      based microbiological methods possess inherent and unavoidable variability,
      recognized by the compendia and which might lead to erroneous conclusion
      pertaining to product quality. Such variability has been associated and
      intrinsically linked with data integrity issues; manufacturers have subsequently
      been encouraged by regulatory authorities to introduce multiple microbiologists
      or checks to prevent such issues. Understanding microbiological variability is
      essential such that genuine data integrity issues are identified. Furthermore, a
      range of meaningful preventative strategies are feasible beyond increasing the
      capacity of the quality control microbiological laboratory. This short review
      describes the legislative requirements, inherent microbiological variability, and
      realistic actions and activities that genuinely assure patient safety.

PMID- 29030530
TI  - Quality of Medicines in Portugal: A Retrospective Review of Medicine Recalls
      (2000-2015).
AB  - INFARMED, the Portuguese national health authority, alerts the general public and
      health care professionals about quality or safety issues detected in health
      products. The present study analyses recalls of substandard medicines in Portugal
      between 2005 and 2015. All 338 alerts for medicine recalls were analysed, which
      represents a total of 378 drugs withdrawn. Despite the fact that the total number
      of medicine alerts has increased during the past decade, the number of actual
      medicine recalls remained relatively constant. The number of batches affected in
      each recall varies from only one to several batches. In addition, 294 of the
      alerts are related to voluntary recalls, that is, those initiated by the
      marketing authorisation holder, whereas only 40 were mandatory recalls. There are
      marketing authorisation holders that have had several medicine recalls over the
      period studied. The main cause of product recall was the pharmaceutical dosage
      form, followed by packaging problems. Forty-two percent of the withdrawn
      medicines are from solid oral forms, a value slightly higher than that obtained
      for the injectables group. Finally, substandard medicines have been accessible in
      the Portuguese market for a period that varied between one month and over four
      years. The data seem to show that the number of substandard medicines in Portugal
      has not been increasing. However, this may be due to a variety of causes, that
      is, better performance of the industry, non-detection of these cases, and so
      on.LAY ABSTRACT: INFARMED, the Portuguese national health authority, alerts the
      general public and health care professionals about quality or safety issues
      detected in health products. The present study analyses market recalls of
      substandard medicines in Portugal between 2005 and 2015. All 338 alerts for
      medicine recalls were analysed, which represents a total of 378 drugs withdrawn.
      Despite the fact that the total number of medicine alerts has increased during
      the past decade, the number of actual medicine recalls has remained relatively
      constant. In addition, 294 of the alerts are related to voluntary recalls, that
      is, initiated by the marketing authorisation holder, whereas only 40 were
      mandatory recalls. There are marketing authorisation holders that have had
      several medicine recalls over the period studied. It was also found that
      substandard medicines have been accessible in the Portuguese market for a period
      that varied between 1 month and over 4 years. The data seem to show that the
      number of substandard medicines in Portugal has not been increasing. However,
      this may be due to a variety of causes, that is, better performance of the
      industry, non-detection of these cases, and so on.

PMID- 29030531
TI  - Impact of Drug Formulation Variables on Silicone Oil Structure and Functionality
      of Prefilled Syringe System.
AB  - Use of prefilled syringes to self-administer biologics via subcutaneous
      administration provides convenience to patients. The barrel interior of prefilled
      syringes is typically coated with silicone oil for lubrication to aid plunger
      movement at the time of administration. This study intended to evaluate the
      impact of formulation variables on the silicone oil on the barrel interior
      surface. Characterization techniques including syringe glide force, break loose
      force, Schlieren imaging, contact angle, inductively coupled plasma spectrometry,
      and thin film interference reflectometry were used in assessing the interactions.
      Data indicated that formulation variables such as pH, buffer/tonicity agent type
      and concentration, and surfactant present in the formulation can effect silicone
      oil lubrication of prefilled syringes, leading to changes in functional
      properties of the syringe over time. Syringe samples containing acetate and
      histidine buffers showed an increase in glide force at accelerated storage
      temperature conditions, but the change was minimal at 5  degrees C. The samples
      with the highest glide force correlated with the presence of mannitol in
      combination with sodium acetate buffer. Sodium chloride had lesser impact on
      glide force than mannitol. Samples with higher glide force exhibited a
      substantial change in the silicone oil layer of the syringe, as observed with
      Schlieren imaging, as well as a significant reduction in surface hydrophobicity,
      as demonstrated through contact angle measurement. These data indicated that the
      structure of the siliconized surface can change over time in contact with
      different formulations. During formulation development of drug products in
      prefilled syringes, in addition to potential impact on molecule stability, the
      selection of formulation variables should also be guided by assessing the impact
      to syringe functionality with the glide force as one of the key parameters.LAY
      ABSTRACT: Self-administering drug products packaged in prefilled syringes
      provides convenience to patients. The interior of a prefilled glass syringe is
      typically lubricated with silicone oil for easy plunger movement during
      injection. This article discusses the impact of formulation excipients on
      silicone oil coating inside the syringe. Characterization techniques were used to
      assess the ease of plunger movement and structure of the silicone coating. Data
      indicate formulation excipients can affect silicone oil distribution of prefilled
      syringes, leading to an increase in plunger glide force at accelerated storage
      temperature conditions. The increase in glide force within a prefilled syringe
      with or without an auto-injector can have an impact on dose accuracy and user
      experience. Syringes with a higher plunger glide force appeared to exhibit a
      change over time in surface energy and structure of the silicone oil layer in
      contact with particular formulations.

PMID- 29030532
TI  - Mechanistic Investigation on Grinding-Induced Subvisible Particle Formation
      during Mixing and Filling of Monoclonal Antibody Formulations.
AB  - Processing equipment involving grinding of two solid surfaces has been
      demonstrated to induce subvisible particle formation in monoclonal antibody drug
      product manufacturing processes. This study elucidated potential stress types
      associated with grinding action to identify the stress mechanism responsible for
      subvisible particle formation. Several potential stress types can be associated
      with the grinding action, including interfacial stresses (air-liquid and liquid
      solid), hydraulic/mechanical shear stress, cavitation, nucleation of stressed
      protein molecules, and localized thermal stress. More than one stress type can
      synergically affect monoclonal antibody product quality, making it challenging to
      determine the primary mode of stress. Our strategy was to assess and rule out
      some stress types through platform knowledge, rational judgments, or via small
      scale models, for example, rheometer/rotator-stator homogenizer for
      hydraulic/mechanical shear stress, sonicator for cavitation, etc. These models
      may not provide direct evidence but can offer rational correlations. Cavitation,
      as demonstrated by sonication, proved to be quite detrimental to monoclonal
      antibody molecules in forming not just subvisible particles but also soluble high
      molecular-weight species as well as low-molecular-weight species. This outcome
      was not consistent with that of grinding monoclonal antibodies between the
      impeller and the drive unit of a bottom-mounted mixer or between the piston and
      the housing of a rotary piston pump, both of which formed only subvisible
      particles without obvious high-molecular-weight species and low-molecular-weight
      species. In addition, a p-nitrophenol model suggested that cavitation in the
      bottom-mounted mixer is barely detectable. We attributed the grinding-induced,
      localized thermal effect to be the primary stress to subvisible particle
      formation based on a high-temperature, spray-drying model. The heat effect of
      spray drying also caused subvisible particles, in the absence of significant high
      molecular-weight species and low-molecular-weight species, in spray-dried
      monoclonal antibody powders. This investigation provides a mechanistic
      understanding of the underlying stress mechanism leading to monoclonal antibody
      subvisible particle formation as the result of drug product processing involving
      grinding of solid surfaces.LAY ABSTRACT: Subvisible particles present in
      therapeutic protein formulations could adversely affect drug product safety and
      efficacy. We previously illustrated that grinding action of the solid surfaces in
      some bottom-mounted mixers and piston pump is responsible for subvisible particle
      formation of monoclonal antibody formulations. In this study, we delved into
      mechanistic understanding of the stress types associated with solid surface
      grinding. The approach was to employ several scale-down stress models with known
      stress types. Protein formulations stressed in these models were analytically
      characterized for subvisible particles and other degradants. Some commonly known
      stress types-such as air-liquid interface, mechanical stress, cavitation,
      nucleation, and thermal effect-were assessed in this study. The stress model
      yielding a degradation profile matching that of bottom-mounted mixers and piston
      pump warranted further assessment. Localized, thermal stress proved to be the
      most feasible mechanism. This study, along with previously published results, may
      further advance our understanding of these particular drug product manufacturing
      processes and benefit scientists and engineers in overcoming these development
      challenges.

PMID- 29030533
TI  - Progress towards TB reduction targets is faltering, report finds.

PMID- 29030534
TI  - Herpes Simplex Virus 1, Macrophages, and the Cornea.

PMID- 29030536
TI  - Classic Spotlight, 2008 and 2009: Articles of Significant Interest Selected from
      the Journal of Virology Archives by the Editors.

PMID- 29030535
TI  - Reply to "Herpes Simplex Virus 1, Macrophages, and the Cornea".

PMID- 29030537
TI  - ATP/ADP turnover and import of glycolytic ATP into mitochondria in cancer cells
      is independent of the adenine nucleotide translocator.

PMID- 29030538
TI  - Proteasomes beyond proteolysis: Roles in heterochromatin maintenance.
AB  - In addition to its proteolytic roles, the 26S proteasome is involved in
      regulating transcription and in promoting sites of active chromatin. In this
      report, Seo et al. provide evidence that the non-proteolytic 19S subunit of the
      26S proteasome also regulates the spreading of inactive chromatin referred to as
      heterochromatin, suggesting further non-canonical roles of the proteasome in gene
      expression.

PMID- 29030539
TI  - The Herbert Tabor Best Paper Awards: Celebrating young authors who contribute top
      content to JBC.

PMID- 29030540
TI  - Hypoxia-Induced Activation of JAK/STAT3 Signaling Pathway Promotes Trophoblast
      Cell Viability and Angiogenesis in Preeclampsia.
AB  - BACKGROUND To explore the effect of hypoxic preconditioning on the JAK/STAT3
      signaling pathway and its effect on trophoblast cell viability and angiogenesis
      in preeclampsia (PE). MATERIAL AND METHODS Placental tissues from normal pregnant
      women and PE patients were collected to detect the expression levels of JAK and
      STAT3. Trophoblast cells separated from the PE patients were assigned to 4
      groups. The expression levels of phosphorylated p-JAK and p-STAT3 were measured
      by Western blot. Cell viability, colony-forming ability, and cell apoptosis were
      assessed. The levels of vascular endothelial growth factor (VEGF), basic
      fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF) were
      determined by enzyme-linked immunosorbent assay (ELISA). RESULTS The expression
      levels of JAK and STAT3 were higher in the placental tissues of PE patients than
      in those of normal pregnant women. Compared with the blank group, in the hypoxia
      group the expression levels of p-JAK and p-STAT3 were increased, cell viability
      was promoted, the number of colonies was increased, cell apoptosis was inhibited,
      and the levels of VEGF, bFGF, and HGF were all elevated. However, in comparison
      with the hypoxia group, the expression levels of p-JAK and p-STAT3 were reduced,
      the cell viability was inhibited, the colonies were decreased, the levels of
      VEGF, bFGF, and HGF were all decreased, and cell apoptosis was promoted in the
      hypoxia + si-JAK group. CONCLUSIONS These findings indicate that hypoxic
      preconditioning may contribute to activation of the JAK/STAT3 signaling pathway,
      thus promoting trophoblast cell viability and angiogenesis in PE.

PMID- 29030541
TI  - Inference of RNA decay rate from transcriptional profiling highlights the
      regulatory programs of Alzheimer's disease.
AB  - The abundance of mRNA is mainly determined by the rates of RNA transcription and
      decay. Here, we present a method for unbiased estimation of differential mRNA
      decay rate from RNA-sequencing data by modeling the kinetics of mRNA metabolism.
      We show that in all primary human tissues tested, and particularly in the central
      nervous system, many pathways are regulated at the mRNA stability level. We
      present a parsimonious regulatory model consisting of two RNA-binding proteins
      and four microRNAs that modulate the mRNA stability landscape of the brain, which
      suggests a new link between RBFOX proteins and Alzheimer's disease. We show that
      downregulation of RBFOX1 leads to destabilization of mRNAs encoding for synaptic
      transmission proteins, which may contribute to the loss of synaptic function in
      Alzheimer's disease. RBFOX1 downregulation is more likely to occur in older and
      female individuals, consistent with the association of Alzheimer's disease with
      age and gender."mRNA abundance is determined by the rates of transcription and
      decay. Here, the authors propose a method for estimating the rate of differential
      mRNA decay from RNA-seq data and model mRNA stability in the brain, suggesting a
      link between mRNA stability and Alzheimer's disease."

PMID- 29030542
TI  - Observation of spin-orbit effects with spin rotation symmetry.
AB  - The spin-orbit interaction enables interconversion between a charge current and a
      spin current. It is usually believed that in a nonmagnetic metal (NM) or at a
      NM/ferromagnetic metal (FM) bilayer interface, the symmetry of spin-orbit effects
      requires that the spin current, charge current, and spin orientation are all
      orthogonal to each other. Here we demonstrate the presence of spin-orbit effects
      near the NM/FM interface that exhibit a very different symmetry, hereafter
      referred to as spin-rotation symmetry, from the conventional spin Hall effect
      while the spin polarization is rotating about the magnetization. These results
      imply that a perpendicularly polarized spin current can be generated with an in
      plane charge current simply by use of a FM/NM bilayer with magnetization
      collinear to the charge current. The ability to generate a spin current with
      arbitrary polarization using typical magnetic materials will benefit the
      development of magnetic memories.Converting charge to spin currents using spin
      orbit interactions has useful applications in spintronics but symmetry
      constraints can limit the control over spin polarization. Here the authors
      demonstrate spin-orbit effects with a different symmetry, which could help
      generate arbitrary spin polarizations.

PMID- 29030543
TI  - Counteracting structural errors in ensemble forecast of influenza outbreaks.
AB  - For influenza forecasts generated using dynamical models, forecast inaccuracy is
      partly attributable to the nonlinear growth of error. As a consequence,
      quantification of the nonlinear error structure in current forecast models is
      needed so that this growth can be corrected and forecast skill improved. Here, we
      inspect the error growth of a compartmental influenza model and find that a
      robust error structure arises naturally from the nonlinear model dynamics. By
      counteracting these structural errors, diagnosed using error breeding, we develop
      a new forecast approach that combines dynamical error correction and statistical
      filtering techniques. In retrospective forecasts of historical influenza
      outbreaks for 95 US cities from 2003 to 2014, overall forecast accuracy for
      outbreak peak timing, peak intensity and attack rate, are substantially improved
      for predicted lead times up to 10 weeks. This error growth correction method can
      be generalized to improve the forecast accuracy of other infectious disease
      dynamical models.Inaccuracy of influenza forecasts based on dynamical models is
      partly due to nonlinear error growth. Here the authors address the error
      structure of a compartmental influenza model, and develop a new improved forecast
      approach combining dynamical error correction and statistical filtering
      techniques.

PMID- 29030544
TI  - Experimental certification of millions of genuinely entangled atoms in a solid.
AB  - Quantum theory predicts that entanglement can also persist in macroscopic
      physical systems, albeit difficulties to demonstrate it experimentally remain.
      Recently, significant progress has been achieved and genuine entanglement between
      up to 2900 atoms was reported. Here, we demonstrate 16 million genuinely
      entangled atoms in a solid-state quantum memory prepared by the heralded
      absorption of a single photon. We develop an entanglement witness for quantifying
      the number of genuinely entangled particles based on the collective effect of
      directed emission combined with the non-classical nature of the emitted light.
      The method is applicable to a wide range of physical systems and is effective
      even in situations with significant losses. Our results clarify the role of
      multipartite entanglement in ensemble-based quantum memories and demonstrate the
      accessibility to certain classes of multipartite entanglement with limited
      experimental control.The presence of entanglement in macroscopic systems is
      notoriously difficult to observe. Here, the authors develop a witness which allow
      them to demonstrate entanglement between millions of atoms in a solid-state
      quantum memory prepared by the heralded absorption of a single photon.

PMID- 29030546
TI  - Spontaneous jumping, bouncing and trampolining of hydrogel drops on a heated
      plate.
AB  - The contact between liquid drops and hot solid surfaces is of practical
      importance for industrial processes, such as thermal spraying and spray cooling.
      The contact and bouncing of solid spheres is also an important event encountered
      in ball milling, powder processing, and everyday activities, such as ball sports.
      Using high speed video microscopy, we demonstrate that hydrogel drops, initially
      at rest on a surface, spontaneously jump upon rapid heating and continue to
      bounce with increasing amplitudes. Jumping is governed by the surface
      wettability, surface temperature, hydrogel elasticity, and adhesion. A
      combination of low-adhesion impact behavior and fast water vapor formation
      supports continuous bouncing and trampolining. Our results illustrate how the
      interplay between solid and liquid characteristics of hydrogels results in
      intriguing dynamics, as reflected by spontaneous jumping, bouncing, trampolining,
      and extremely short contact times.Drops of liquid on a hot surface can exhibit
      fascinating behaviour such as the Leidenfrost effect in which drops hover on a
      vapour layer. Here Pham et al. show that when hydrogel drops are placed on a
      rapidly heated plate they bounce to increasing heights even if they were
      initially at rest.

PMID- 29030545
TI  - Fructose-1,6-bisphosphate couples glycolytic flux to activation of Ras.
AB  - Yeast and cancer cells share the unusual characteristic of favoring fermentation
      of sugar over respiration. We now reveal an evolutionary conserved mechanism
      linking fermentation to activation of Ras, a major regulator of cell
      proliferation in yeast and mammalian cells, and prime proto-oncogene product. A
      yeast mutant (tps1?) with overactive influx of glucose into glycolysis and
      hyperaccumulation of Fru1,6bisP, shows hyperactivation of Ras, which causes its
      glucose growth defect by triggering apoptosis. Fru1,6bisP is a potent activator
      of Ras in permeabilized yeast cells, likely acting through Cdc25. As in yeast,
      glucose triggers activation of Ras and its downstream targets MEK and ERK in
      mammalian cells. Biolayer interferometry measurements show that physiological
      concentrations of Fru1,6bisP stimulate dissociation of the pure Sos1/H-Ras
      complex. Thermal shift assay confirms direct binding to Sos1, the mammalian
      ortholog of Cdc25. Our results suggest that the Warburg effect creates a vicious
      cycle through Fru1,6bisP activation of Ras, by which enhanced fermentation
      stimulates oncogenic potency.Yeast and cancer cells both favor sugar fermentation
      in aerobic conditions. Here the authors describe a conserved mechanism from yeast
      to mammals where the glycolysis intermediate fructose-1,6-bisphosphate binds
      Cdc25/Sos1 and couples increased glycolytic flux to increased Ras proto
      oncoprotein activity.

PMID- 29030547
TI  - The Hidden Flow Structure and Metric Space of Network Embedding Algorithms Based
      on Random Walks.
AB  - Network embedding which encodes all vertices in a network as a set of numerical
      vectors in accordance with it's local and global structures, has drawn widespread
      attention. Network embedding not only learns significant features of a network,
      such as the clustering and linking prediction but also learns the latent vector
      representation of the nodes which provides theoretical support for a variety of
      applications, such as visualization, link prediction, node classification, and
      recommendation. As the latest progress of the research, several algorithms based
      on random walks have been devised. Although those algorithms have drawn much
      attention for their high scores in learning efficiency and accuracy, there is
      still a lack of theoretical explanation, and the transparency of those algorithms
      has been doubted. Here, we propose an approach based on the open-flow network
      model to reveal the underlying flow structure and its hidden metric space of
      different random walk strategies on networks. We show that the essence of
      embedding based on random walks is the latent metric structure defined on the
      open-flow network. This not only deepens our understanding of random- walk-based
      embedding algorithms but also helps in finding new potential applications in
      network embedding.

PMID- 29030548
TI  - Evidence of indirect gap in monolayer WSe2.
AB  - Monolayer transition metal dichalcogenides, such as MoS2 and WSe2, have been
      known as direct gap semiconductors and emerged as new optically active materials
      for novel device applications. Here we reexamine their direct gap properties by
      investigating the strain effects on the photoluminescence of monolayer MoS2 and
      WSe2. Instead of applying stress, we investigate the strain effects by imaging
      the direct exciton populations in monolayer WSe2-MoS2 and MoSe2-WSe2 lateral
      heterojunctions with inherent strain inhomogeneity. We find that unstrained
      monolayer WSe2 is actually an indirect gap material, as manifested in the
      observed photoluminescence intensity-energy correlation, from which the
      difference between the direct and indirect optical gaps can be extracted by
      analyzing the exciton thermal populations. Our findings combined with the
      estimated exciton binding energy further indicate that monolayer WSe2 exhibits an
      indirect quasiparticle gap, which has to be reconsidered in further studies for
      its fundamental properties and device applications.Monolayer transition metal
      dichalcogenides have so far been thought to be direct bandgap semiconductors.
      Here, the authors revisit this assumption and find that unstrained monolayer WSe2
      is an indirect-gap material, as evidenced by the observed photoluminescence
      intensity-energy correlation.

PMID- 29030549
TI  - Evidence of local and regional freshening of Northeast Greenland coastal waters.
AB  - The supply of freshwater to fjord systems in Greenland is increasing as a result
      of climate change-induced acceleration in ice sheet melt. However, insight into
      the marine implications of the melt water is impaired by lack of observations
      demonstrating the fate of freshwater along the Greenland coast and providing
      evaluation basis for ocean models. Here we present 13 years of summer
      measurements along a 120 km transect in Young Sound, Northeast Greenland and show
      that sub-surface coastal waters are decreasing in salinity with an average rate
      of 0.12 +/- 0.05 per year. This is the first observational evidence of a
      significant freshening on decadal scale of the waters surrounding the ice sheet
      and comes from a region where ice sheet melt has been less significant. It
      implies that ice sheet dynamics in Northeast Greenland could be of key importance
      as freshwater is retained in southward flowing coastal currents thus reducing
      density of water masses influencing major deep water formation areas in the
      Subarctic Atlantic Ocean. Ultimately, the observed freshening could have
      implications for the Atlantic meridional overturning circulation.

PMID- 29030550
TI  - A conserved KLF-autophagy pathway modulates nematode lifespan and mammalian age
      associated vascular dysfunction.
AB  - Loss of protein and organelle quality control secondary to reduced autophagy is a
      hallmark of aging. However, the physiologic and molecular regulation of autophagy
      in long-lived organisms remains incompletely understood. Here we show that the
      Kruppel-like family of transcription factors are important regulators of
      autophagy and healthspan in C. elegans, and also modulate mammalian vascular age
      associated phenotypes. Kruppel-like family of transcription factor deficiency
      attenuates autophagy and lifespan extension across mechanistically distinct
      longevity nematode models. Conversely, Kruppel-like family of transcription
      factor overexpression extends nematode lifespan in an autophagy-dependent manner.
      Furthermore, we show the mammalian vascular factor Kruppel-like family of
      transcription factor 4 has a conserved role in augmenting autophagy and improving
      vessel function in aged mice. Kruppel-like family of transcription factor 4
      expression also decreases with age in human vascular endothelium. Thus, Kruppel
      like family of transcription factors constitute a transcriptional regulatory
      point for the modulation of autophagy and longevity in C. elegans with conserved
      effects in the murine vasculature and potential implications for mammalian
      vascular aging.KLF family transcription factors (KLFs) regulate many cellular
      processes, including proliferation, survival and stress responses. Here, the
      authors position KLFs as important regulators of autophagy and lifespan in C.
      elegans, a role that may extend to the modulation of age-associated vascular
      phenotypes in mammals.

PMID- 29030551
TI  - Kif2 localizes to a subdomain of cortical endoplasmic reticulum that drives
      asymmetric spindle position.
AB  - Asymmetric positioning of the mitotic spindle is a fundamental process
      responsible for creating sibling cell size asymmetry; however, how the cortex
      causes the depolymerization of astral microtubules during asymmetric spindle
      positioning has remained elusive. Early ascidian embryos possess a large cortical
      subdomain of endoplasmic reticulum (ER) that causes asymmetric spindle
      positioning driving unequal cell division. Here we show that the microtubule
      depolymerase Kif2 localizes to this subdomain of cortical ER. Rapid live-cell
      imaging reveals that microtubules are less abundant in the subdomain of cortical
      ER. Inhibition of Kif2 function prevents the development of mitotic aster
      asymmetry and spindle pole movement towards the subdomain of cortical ER, whereas
      locally increasing microtubule depolymerization causes exaggerated asymmetric
      spindle positioning. This study shows that the microtubule depolymerase Kif2 is
      localized to a cortical subdomain of endoplasmic reticulum that is involved in
      asymmetric spindle positioning during unequal cell division.Early ascidian
      embryos have a cortical subdomain of endoplasmic reticulum (ER) that controls
      asymmetric spindle positioning driving unequal cell division. Here the authors
      show that the microtubule depolymerase Kif2 is localized to a cortical subdomain
      of the ER that is involved in asymmetric spindle positioning.

PMID- 29030552
TI  - BAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic
      cells.
AB  - Toll-like receptors (TLR) are essential components of the innate immune system.
      Several accessory proteins, such as UNC93B1, are required for transport and
      activation of nucleic acid sensing Toll-like receptors in endosomes. Here, we
      show that BAD-LAMP (LAMP5) controls TLR9 trafficking to LAMP1+ late endosomes in
      human plasmacytoid dendritic cells (pDC), leading to NF-kappaB activation and TNF
      production upon DNA detection. An inducible VAMP3+/LAMP2+/LAMP1- endolysosome
      compartment exists in pDCs from which TLR9 activation triggers type I interferon
      expression. BAD-LAMP-silencing enhances TLR9 retention in this compartment and
      consequent downstream signalling events. Conversely, sustained BAD-LAMP
      expression in pDCs contributes to their lack of type I interferon production
      after exposure to a TGF-beta-positive microenvironment or isolation from human
      breast tumours. Hence, BAD-LAMP limits interferon expression in pDCs indirectly,
      by promoting TLR9 sorting to late endosome compartments at steady state and in
      response to immunomodulatory cues.TLR9 is highly expressed by plasmacytoid
      dendritic cells and detects nucleic acids, but to discriminate between host and
      microbial nucleic acids TLR9 is sorted into different endosomal compartments.
      Here the authors show that BAD-LAMP limits type 1 interferon responses by sorting
      TLR9 to late endosomal compartments.

PMID- 29030553
TI  - Actomyosin polarisation through PLC-PKC triggers symmetry breaking of the mouse
      embryo.
AB  - Establishment of cell polarity in the mammalian embryo is fundamental for the
      first cell fate decision that sets aside progenitor cells for both the new
      organism and the placenta. Yet the sequence of events and molecular mechanism
      that trigger this process remain unknown. Here, we show that de novo polarisation
      of the mouse embryo occurs in two distinct phases at the 8-cell stage. In the
      first phase, an apical actomyosin network is formed. This is a pre-requisite for
      the second phase, in which the Par complex localises to the apical domain,
      excluding actomyosin and forming a mature apical cap. Using a variety of
      approaches, we also show that phospholipase C-mediated PIP2 hydrolysis is
      necessary and sufficient to trigger the polarisation of actomyosin through the
      Rho-mediated recruitment of myosin II to the apical cortex. Together, these
      results reveal the molecular framework that triggers de novo polarisation of the
      mouse embryo.The molecular trigger that establishes cell polarity in the
      mammalian embryo is unclear. Here, the authors show that de novo polarisation of
      the mouse embryo at the 8-cell stage is directed by Phospholipase C and Protein
      kinase C and occurs in two phases: polarisation of actomyosin followed by the Par
      complex.

PMID- 29030554
TI  - HDX reveals the conformational dynamics of DNA sequence specific VDR co-activator
      interactions.
AB  - The vitamin D receptor/retinoid X receptor-alpha heterodimer (VDRRXRalpha)
      regulates bone mineralization via transcriptional control of osteocalcin (BGLAP)
      gene and is the receptor for 1alpha,25-dihydroxyvitamin D3 (1,25D3). However,
      supra-physiological levels of 1,25D3 activates the calcium-regulating gene TRPV6
      leading to hypercalcemia. An approach to attenuate this adverse effect is to
      develop selective VDR modulators (VDRMs) that differentially activate BGLAP but
      not TRPV6. Here we present structural insight for the action of a VDRM compared
      with agonists by employing hydrogen/deuterium exchange. Agonist binding directs
      crosstalk between co-receptors upon DNA binding, stabilizing the activation
      function 2 (AF2) surfaces of both receptors driving steroid receptor co-activator
      1 (SRC1) interaction. In contrast, AF2 of VDR within VDRM:BGLAP bound heterodimer
      is more vulnerable for large stabilization upon SRC1 interaction compared with
      VDRM:TRPV6 bound heterodimer. These results reveal that the combination of ligand
      structure and DNA sequence tailor the transcriptional activity of VDR toward
      specific target genes.The vitamin D receptor/retinoid X receptor-alpha
      heterodimer (VDRRXRalpha) regulates bone mineralization. Here the authors employ
      hydrogen/deuterium exchange (HDX) mass spectrometry to study the conformational
      dynamics of VDRRXRalpha and give mechanistic insights into how VDRRXRalpha
      controls the transcriptional activity of specific genes.

PMID- 29030555
TI  - Highly compressed water structure observed in a perchlorate aqueous solution.
AB  - The discovery by the Phoenix Lander of calcium and magnesium perchlorates in
      Martian soil samples has fueled much speculation that flows of perchlorate brines
      might be the cause of the observed channeling and weathering in the surface.
      Here, we study the structure of a mimetic of Martian water, magnesium perchlorate
      aqueous solution at its eutectic composition, using neutron diffraction in
      combination with hydrogen isotope labeling and empirical potential structure
      refinement. We find that the tetrahedral structure of water is heavily perturbed,
      the effect being equivalent to pressurizing pure water to pressures of order 2
      GPa or more. The Mg2+ and ClO4- ions appear charge-ordered, confining the water
      on length scales of order 9 A, preventing ice formation at low temperature. This
      may explain the low evaporation rates and high deliquescence of these salt
      solutions, which are essential for stability within the low relative humidity
      environment of the Martian atmosphere.Significant amounts of different
      perchlorate salts have been discovered on the surface of Mars. Here, the authors
      show that magnesium perchlorate has a major impact on water structure in
      solution, providing insight into how an aqueous fluid might exist under the sub
      freezing conditions present on Mars.

PMID- 29030556
TI  - Entanglement between more than two hundred macroscopic atomic ensembles in a
      solid.
AB  - There are both fundamental and practical motivations for studying whether quantum
      entanglement can exist in macroscopic systems. However, multiparty entanglement
      is generally fragile and difficult to quantify. Dicke states are multiparty
      entangled states where a single excitation is delocalized over many systems.
      Building on previous work on quantum memories for photons, we create a Dicke
      state in a solid by storing a single photon in a crystal that contains many large
      atomic ensembles with distinct resonance frequencies. The photon is re-emitted at
      a well-defined time due to an interference effect analogous to multi-slit
      diffraction. We derive a lower bound for the number of entangled ensembles based
      on the contrast of the interference and the single-photon character of the input,
      and we experimentally demonstrate entanglement between over two hundred
      ensembles, each containing a billion atoms. We also illustrate the fact that each
      individual ensemble contains further entanglement.Multipartite entanglement is of
      both fundamental and practical interest, but is notoriously difficult to witness
      and characterise. Here, Zarkeshian et al. demonstrate multipartite entanglement
      in an atomic frequency comb storing a single photon in a Dicke state spread over
      a macroscopic ensemble.

PMID- 29030557
TI  - Heading representations in primates are compressed by saccades.
AB  - Perceptual illusions help to understand how sensory signals are decoded in the
      brain. Here we report that the opposite approach is also applicable, i.e.,
      results from decoding neural activity from monkey extrastriate visual cortex
      correctly predict a hitherto unknown perceptual illusion in humans. We record
      neural activity from monkey medial superior temporal (MST) and ventral
      intraparietal (VIP) area during presentation of self-motion stimuli and
      concurrent reflexive eye movements. A heading-decoder performs veridically during
      slow eye movements. During fast eye movements (saccades), however, the decoder
      erroneously reports compression of heading toward straight ahead. Functional
      equivalents of macaque areas MST and VIP have been identified in humans, implying
      a perceptual correlate (illusion) of this perisaccadic decoding error. Indeed, a
      behavioral experiment in humans shows that perceived heading is perisaccadically
      compressed toward the direction of gaze. Response properties of primate areas MST
      and VIP are consistent with being the substrate of the newly described visual
      illusion.Macaque higher visual areas MST and VIP encode heading direction based
      on self-motion stimuli. Here the authors show that, while making saccades, the
      heading direction decoded from the neural responses is compressed toward straight
      ahead, and independently demonstrate a perceptual illusion in humans based on
      this perisaccadic decoding error.

PMID- 29030558
TI  - Optical conversion of pure spin currents in hybrid molecular devices.
AB  - Carbon-based molecules offer unparalleled potential for THz and optical devices
      controlled by pure spin currents: a low-dissipation flow of electronic spins with
      no net charge displacement. However, the research so far has been focused on the
      electrical conversion of the spin imbalance, where molecular materials are used
      to mimic their crystalline counterparts. Here, we use spin currents to access the
      molecular dynamics and optical properties of a fullerene layer. The spin mixing
      conductance across Py/C60 interfaces is increased by 10% (5 * 1018 m-2) under
      optical irradiation. Measurements show up to a 30% higher light absorbance and a
      factor of 2 larger photoemission during spin pumping. We also observe a 0.15 THz
      slowdown and a narrowing of the vibrational peaks. The effects are attributed to
      changes in the non-radiative damping and energy transfer. This opens new research
      paths in hybrid magneto-molecular optoelectronics, and the optical detection of
      spin physics in these materials.Carbon-based molecules could prove useful in
      terahertz and optical devices controlled by pure spin currents. Here, conversely,
      the authors use spin currents to probe molecular dynamics and enhance the optical
      response of a fullerene layer, enabling hybrid magneto-molecular optoelectronic
      devices.

PMID- 29030559
TI  - Understanding seed-mediated growth of gold nanoclusters at molecular level.
AB  - The continuous development of total synthesis chemistry has allowed many organic
      and biomolecules to be produced with known synthetic history-that is, a complete
      set of step reactions in their synthetic routes. Here, we extend such molecular
      level precise reaction routes to nanochemistry, particularly to a seed-mediated
      synthesis of inorganic nanoparticles. By systematically investigating the time
      dependent abundance of 35 intermediate species in total, we map out relevant step
      reactions in a model size growth reaction from molecularly pure Au25 to Au44
      nanoparticles. The size growth of Au nanoparticles involves two different size
      evolution processes (monotonic LaMer growth and volcano-shaped aggregative
      growth), which are driven by a sequential 2-electron boosting of the valence
      electron count of Au nanoparticles. Such fundamental findings not only provide
      guiding principles to produce other sizes of Au nanoparticles (e.g., Au38), but
      also represent molecular-level insights on long-standing puzzles in
      nanochemistry, including LaMer growth, aggregative growth, and digestive
      ripening.Synthetic nanochemistry currently lacks the molecular step-by-step
      routes afforded to organic chemistry by total synthesis. Here, the authors track
      the seeded growth of atom-precise gold nanoclusters using mass spectrometry,
      revealing that the clusters evolve through a series of intermediates in two
      electron steps.

PMID- 29030560
TI  - Risk of Sarcopenia and Osteoporosis in Male Tuberculosis Survivors: Korea
      National Health and Nutrition Examination Survey.
AB  - Short-term prospective studies have suggested that pulmonary tuberculosis (TB)
      preludes permanent loss of lean tissue and fat mass even when TB treatment is
      effective. The aim of this study was to estimate the risk of sarcopenia and
      osteoporosis among Korean male TB survivors. Data of the population-based, Korea
      National Health and Nutrition Examination Survey (KNHANES) (2008-2011) were
      analyzed, including 3,228 males aged 50 years or older who underwent chest X-ray
      (CXR) and dual-energy x-ray absorptiometry (DEXA). TB survivors having both
      medical history and TB scars on CXR had increased risk of sarcopenia (odds ratio
      [OR] 3.44, 95% confidence interval [CI] 1.79-6.68) and osteoporosis (OR 1.75, 95%
      CI 1.04-2.95) after adjusting for age, height, smoking, alcohol, physical
      activity, serum 25-hydroxyvitamin D, parathyroid hormone level, education, and
      fat mass index. Having TB scars on CXR without medical history of TB was an
      independent risk factor of sarcopenia (OR 2.05, 95% CI 1.05-4.00), but not a risk
      factor of osteoporosis. Sarcopenia and low bone mineral density are prevalent in
      pulmonary TB survivors with TB scars on CXR. Medical history of TB with TB scars
      on CXR is an independent risk factor for sarcopenia and osteoporosis.

PMID- 29030561
TI  - Oxidative and anti-oxidative status in muscle of young rats in response to six
      protein diets.
AB  - We investigated the impact of six protein diets on oxidation and anti-oxidation
      status in the muscle of young rats. Rats were fed six protein diets for 14 days,
      including casein (control), and proteins isolated from soy, fish, chicken, pork
      and beef. Grx1, Trx1 and other oxidative metabolic indices in muscle were
      quantified. Compared with the casein diet, the soy protein diet had a similar
      oxidation level, but higher GSH and lower SOD activities. The chicken and fish
      protein groups had lower GSH and higher SOD activities, the pork protein group
      showed lower Grx1 levels than the casein group and the beef protein group showed
      the highest GSH, Grx1 and Trx1 levels as reflected by RT-PCR, Western blotting
      and immunohistochemistry analyses. Intake of meat proteins showed higher ROS and
      T-AOC but lower MDA levels than non-meat proteins, which may be due to the
      increase in Grx1 and Trx1 expression and other antioxidants. Meat proteins are
      more conducive to muscle of growing rats.

PMID- 29030562
TI  - Astrocyte calcium waves propagate proximally by gap junction and distally by
      extracellular diffusion of ATP released from volume-regulated anion channels.
AB  - Wave-like propagation of [Ca2+]i increases is a remarkable intercellular
      communication characteristic in astrocyte networks, intercalating neural circuits
      and vasculature. Mechanically-induced [Ca2+]i increases and their subsequent
      propagation to neighboring astrocytes in culture is a classical model of
      astrocyte calcium wave and is known to be mediated by gap junction and
      extracellular ATP, but the role of each pathway remains unclear. Pharmacologic
      analysis of time-dependent distribution of [Ca2+]i revealed three distinct
      [Ca2+]i increases, the largest being in stimulated cells independent of
      extracellular Ca2+ and inositol 1,4,5-trisphosphate-induced Ca2+ release. In
      addition, persistent [Ca2+]i increases were found to propagate rapidly via gap
      junctions in the proximal region, and transient [Ca2+]i increases were found to
      propagate slowly via extracellular ATP in the distal region. Simultaneous imaging
      of astrocyte [Ca2+]i and extracellular ATP, the latter of which was measured by
      an ATP sniffing cell, revealed that ATP was released within the proximal region
      by volume-regulated anion channel in a [Ca2+]i independent manner. This detailed
      analysis of a classical model is the first to address the different contributions
      of two major pathways of calcium waves, gap junctions and extracellular ATP.

PMID- 29030563
TI  - Methane fluxes from coastal sediments are enhanced by macrofauna.
AB  - Methane and nitrous oxide are potent greenhouse gases (GHGs) that contribute to
      climate change. Coastal sediments are important GHG producers, but the
      contribution of macrofauna (benthic invertebrates larger than 1 mm) inhabiting
      them is currently unknown. Through a combination of trace gas, isotope, and
      molecular analyses, we studied the direct and indirect contribution of two
      macrofaunal groups, polychaetes and bivalves, to methane and nitrous oxide fluxes
      from coastal sediments. Our results indicate that macrofauna increases benthic
      methane efflux by a factor of up to eight, potentially accounting for an
      estimated 9.5% of total emissions from the Baltic Sea. Polychaetes indirectly
      enhance methane efflux through bioturbation, while bivalves have a direct effect
      on methane release. Bivalves host archaeal methanogenic symbionts carrying out
      preferentially hydrogenotrophic methanogenesis, as suggested by analysis of
      methane isotopes. Low temperatures (8  degrees C) also stimulate production of
      nitrous oxide, which is consumed by benthic denitrifying bacteria before it
      reaches the water column. We show that macrofauna contributes to GHG production
      and that the extent is dependent on lineage. Thus, macrofauna may play an
      important, but overlooked role in regulating GHG production and exchange in
      coastal sediment ecosystems.

PMID- 29030564
TI  - Dynamic annealing in Ge studied by pulsed ion beams.
AB  - The formation of radiation damage in Ge above room temperature is dominated by
      complex dynamic annealing processes, involving migration and interaction of
      ballistically-generated point defects. Here, we study the dynamics of radiation
      defects in Ge in the temperature range of 100-160  degrees C under pulsed beam
      irradiation with 500 keV Ar ions when the total ion fluence is split into a train
      of equal square pulses. By varying the passive portion of the beam duty cycle, we
      measure a characteristic time constant of dynamic annealing, which rapidly
      decreases from ~8 to 0.3 ms with increasing temperature. By varying the active
      portion of the beam duty cycle, we measure an effective diffusion length of ~38
      nm at 110  degrees C. Results reveal a major change in the dominant dynamic
      annealing process at a critical transition temperature of ~130  degrees C. The
      two dominant dynamic annealing processes have an order of magnitude different
      activation energies of 0.13 and 1.3 eV.

PMID- 29030565
TI  - Proteolytic signatures define unique thrombin-derived peptides present in human
      wound fluid in vivo.
AB  - The disease burden of failing skin repair and non-healing ulcers is extensive.
      There is an unmet need for new diagnostic approaches to better predict healing
      activity and wound infection. Uncontrolled and excessive protease activity, of
      endogenous or bacterial origin, has been described as a major contributor to
      wound healing impairments. Proteolytic peptide patterns could therefore correlate
      and "report" healing activity and infection. This work describes a proof of
      principle delineating a strategy by which peptides from a selected protein, human
      thrombin, are detected and attributed to proteolytic actions. With a particular
      focus on thrombin-derived C-terminal peptides (TCP), we show that distinct
      peptide patterns are generated in vitro by the human S1 peptidases human
      neutrophil elastase and cathepsin G, and the bacterial M4 peptidases Pseudomonas
      aeruginosa elastase and Staphylococcus aureus aureolysin, respectively.
      Corresponding peptide sequences were identified in wound fluids from acute and
      non-healing ulcers, and notably, one peptide, FYT21 (FYTHVFRLKKWIQKVIDQFGE), was
      only present in wound fluid from non-healing ulcers colonized by P. aeruginosa
      and S. aureus. Our result is a proof of principle pointing at the possibility of
      defining peptide biomarkers reporting distinct proteolytic activities, of
      potential implication for improved diagnosis of wound healing and infection.

PMID- 29030566
TI  - Unobtrusive Nocturnal Heartbeat Monitoring by a Ballistocardiographic Sensor in
      Patients with Sleep Disordered Breathing.
AB  - Sleep disordered breathing (SDB) is known for fluctuating heart rates and an
      increased risk of developing arrhythmias. The current reference for heartbeat
      analysis is an electrocardiogram (ECG). As an unobtrusive alternative, we tested
      a sensor foil for mechanical vibrations to perform a ballistocardiography (BCG)
      and applied a novel algorithm for beat-to-beat cycle length detection. The aim of
      this study was to assess the correlation between beat-to-beat cycle length
      detection by the BCG algorithm and simultaneously recorded ECG. In 21 patients
      suspected for SDB undergoing polysomnography, we compared ECG to simultaneously
      recorded BCG data analysed by our algorithm. We analysed 362.040 heartbeats
      during a total of 93 hours of recording. The baseline beat-to-beat cycle length
      correlation between BCG and ECG was r s  = 0.77 (n = 362040) with a mean absolute
      difference of 15 +/- 162 ms (mean cycle length: ECG 923 +/- 220 ms; BCG 908 +/-
      203 ms). After filtering artefacts and improving signal quality by our algorithm,
      the correlation increased to r s  = 0.95 (n = 235367) with a mean absolute
      difference in cycle length of 4 +/- 72 ms (ECG 920 +/- 196 ms; BCG 916 +/- 194
      ms). We conclude that our algorithm, coupled with a BCG sensor foil provides good
      correlation of beat-to-beat cycle length detection with simultaneously recorded
      ECG.

PMID- 29030567
TI  - Plasmodium falciparum specific helicase 3 is nucleocytoplasmic protein and
      unwinds DNA duplex in 3' to 5' direction.
AB  - Plasmodium falciparum is responsible for most dangerous and prevalent form of
      malaria. The emergence of multi drug resistant parasite hindered the prevention
      of malaria burden worldwide. Helicases are omnipresent enzymes, which play
      important role in nucleic acid metabolism and can be used as potential targets
      for development of novel therapeutics. The genome wide analysis of P. falciparum
      3D7 strain revealed some novel parasite specific helicases, which are not present
      in human host. Here we report the detailed biochemical characterization of P.
      falciparum parasite specific helicase 3 (PfPSH3). The characteristic ATPase and
      helicase activities of PfPSH3 reside in its N-terminal region (PfPSH3N) as it
      contains all the conserved signature motifs whereas the C-terminal does not show
      any detectable biochemical activity. PfPSH3N also shows DNA helicase activity in
      the 3'-5' direction. The immunofluorescence microscopy results show that PSH3 is
      localized in nucleus as well as in cytoplasm during different stages such as
      trophozoite and early schizont stages of intraerythrocytic development. This
      report sets the foundation for further study of parasite specific helicases and
      will be helpful in understanding the parasite biology.

PMID- 29030568
TI  - Cognitive appraisal of environmental stimuli induces emotion-like states in fish.
AB  - The occurrence of emotions in non-human animals has been the focus of debate over
      the years. Recently, an interest in expanding this debate to non-tetrapod
      vertebrates and to invertebrates has emerged. Within vertebrates, the study of
      emotion in teleosts is particularly interesting since they represent a divergent
      evolutionary radiation from that of tetrapods, and thus they provide an insight
      into the evolution of the biological mechanisms of emotion. We report that Sea
      Bream exposed to stimuli that vary according to valence (positive, negative) and
      salience (predictable, unpredictable) exhibit different behavioural,
      physiological and neuromolecular states. Since according to the dimensional
      theory of emotion valence and salience define a two-dimensional affective space,
      our data can be interpreted as evidence for the occurrence of distinctive
      affective states in fish corresponding to each the four quadrants of the core
      affective space. Moreover, the fact that the same stimuli presented in a
      predictable vs. unpredictable way elicited different behavioural, physiological
      and neuromolecular states, suggests that stimulus appraisal by the individual,
      rather than an intrinsic characteristic of the stimulus, has triggered the
      observed responses. Therefore, our data supports the occurrence of emotion-like
      states in fish that are regulated by the individual's perception of environmental
      stimuli.

PMID- 29030569
TI  - Active GSK3beta and an intact beta-catenin TCF complex are essential for the
      differentiation of human myogenic progenitor cells.
AB  - Wnt-beta-catenin signalling is essential for skeletal muscle myogenesis during
      development, but its role in adult human skeletal muscle remains unknown. Here we
      have used human primary CD56Pos satellite cell-derived myogenic progenitors
      obtained from healthy individuals to study the role of Wnt-beta-catenin
      signalling in myogenic differentiation. We show that dephosphorylated beta
      catenin (active-beta-catenin), the central effector of the canonical Wnt cascade,
      is strongly upregulated at the onset of differentiation and undergoes nuclear
      translocation as differentiation progresses. To establish the role of Wnt
      signalling in regulating the differentiation process we manipulated key nodes of
      this pathway through a series of beta-catenin gain-of-function (GSK3 inhibition
      and beta-catenin overexpression) or loss-of-function experiments (dominant
      negative TCF4). Our data showed that manipulation of these critical pathway
      components led to varying degrees of disruption to the normal differentiation
      phenotype indicating the importance of Wnt signalling in regulating this process.
      We reveal an independent necessity for active-beta-catenin in the fusion and
      differentiation of human myogenic progenitors and that dominant negative
      inhibition of TCF4 prevents differentiation completely. Together these data add
      new mechanistic insights into both Wnt signalling and adult human myogenic
      progenitor differentiation.

PMID- 29030570
TI  - New insights into the degradation mechanism of metal-organic frameworks drug
      carriers.
AB  - A versatile method based on Raman microscopy was developed to follow the
      degradation of iron carboxylate Metal Organic Framework (MOF) nano- or micro
      particles in simulated body fluid (phosphate buffer). The analysis of both the
      morphology and chemical composition of individual particles, including
      observation at different regions on the same particle, evidenced the formation of
      a sharp erosion front during particle degradation. Interestingly, this front
      separated an intact non eroded crystalline core from an amorphous shell made of
      an inorganic network. According to Mossbauer spectrometry investigations, the
      shell consists essentially of iron phosphates. Noteworthy, neither drug loading
      nor surface modification affected the integrity of the tridimensional MOF
      network. These findings could be of interest in the further development of next
      generations of MOF drug carriers.

PMID- 29030571
TI  - Objective-lens-free Fiber-based Position Detection with Nanometer Resolution in a
      Fiber Optical Trapping System.
AB  - Position detection with high accuracy is crucial for force calibration of optical
      trapping systems. Most existing position detection methods require high-numerical
      aperture objective lenses, which are bulky, expensive, and difficult to
      miniaturize. Here, we report an affordable objective-lens-free, fiber-based
      position detection scheme with 2 nm spatial resolution and 150 MHz bandwidth.
      This fiber based detection mechanism enables simultaneous trapping and force
      measurements in a compact fiber optical tweezers system. In addition, we achieved
      more reliable signal acquisition with less distortion compared with objective
      based position detection methods, thanks to the light guiding in optical fibers
      and small distance between the fiber tips and trapped particle. As a
      demonstration of the fiber based detection, we used the fiber optical tweezers to
      apply a force on a cell membrane and simultaneously measure the cellular
      response.

PMID- 29030572
TI  - Transgenic Nicotiana benthamiana plants expressing a hairpin RNAi construct of a
      nematode Rs-cps gene exhibit enhanced resistance to Radopholus similis.
AB  - Burrowing nematodes (Radopholus similis) cause severe harm in many agronomic and
      horticultural crops and are very difficult to manage. Cathepsin S is one of the
      most important cysteine proteinases and plays key roles in nematodes and many
      other parasites. To evaluate the effect of in planta RNAi on the control of this
      nematode, a specific fragment from the protease gene, cathepsin S (Rs-cps), was
      cloned into the binary vector pFGC5941 in the forward and reverse orientations to
      construct recombinant plant RNAi vectors. Transgenic Nicotiana benthamiana plants
      expressing Rs-cps dsRNA were obtained and studied. The transcript abundance of Rs
      cps dsRNA appeared to be diverse in the different transgenic lines. Moreover, the
      bioassay results revealed that Rs-cps transgenic N. benthamiana plants were
      resistant to R. similis and the transcription level of Rs-cps in R. similis was
      drastically decreased. In addition, the reproduction and hatching rate of R.
      similis isolated from the Rs-cps transgenic plants were also significantly
      reduced. Our results suggest that Rs-cps is essential for the reproduction and
      pathogenicity of R. similis. This is the first study to employ in planta RNAi
      approach to target the Rs-cps gene for the control of plant parasitic nematodes.

PMID- 29030573
TI  - Adjusting the catalytic properties of cobalt ferrite nanoparticles by pulsed
      laser fragmentation in water with defined energy dose.
AB  - Highly active, structurally disordered CoFe2O4/CoO electrocatalysts are
      synthesized by pulsed laser fragmentation in liquid (PLFL) of a commercial
      CoFe2O4 powder dispersed in water. A partial transformation of the CoFe2O4 educt
      to CoO is observed and proposed to be a thermal decomposition process induced by
      the picosecond pulsed laser irradiation. The overpotential in the OER in aqueous
      alkaline media at 10 mA cm-2 is reduced by 23% compared to the educt down to 0.32
      V with a Tafel slope of 71 mV dec-1. Importantly, the catalytic activity is
      systematically adjustable by the number of PLFL treatment cycles. The occurrence
      of thermal melting and decomposition during one PLFL cycle is verified by
      modelling the laser beam energy distribution within the irradiated colloid volume
      and comparing the by single particles absorbed part to threshold energies.
      Thermal decomposition leads to a massive reduction in particle size and crystal
      transformations towards crystalline CoO and amorphous CoFe2O4. Subsequently,
      thermal melting forms multi-phase spherical and network-like particles.
      Additionally, Fe-based layered double hydroxides at higher process cycle
      repetitions emerge as a byproduct. The results show that PLFL is a promising
      method that allows modification of the structural order in oxides and thus access
      to catalytically interesting materials.

PMID- 29030574
TI  - Aggregation behavior and reproductive compatibility in the family Cimicidae.
AB  - Bed bugs (Cimex lectularius) provide a unique opportunity to understand
      speciation and host-associated divergence in parasites. Recently, two sympatric
      but genetically distinct lineages of C. lectularius were identified: one
      associated with humans and one associated with bats. We investigated two
      mechanisms that could maintain genetic differentiation in the field: reproductive
      compatibility (via mating crosses) and aggregation fidelity (via two-choice
      sheltering assays). Effects were assessed at the intra-lineage level (within
      human-associated bed bugs), inter-lineage level (between human- and bat
      associated bed bugs), and inter-species level (between C. lectularius and Cimex
      pipistrelli [bat bug]). Contrary to previous reports, bed bugs were found to be
      reproductively compatible at both the intra- and inter-lineage levels, but not at
      the inter-species level (although three hybrids were produced, one of which
      developed into an adult). Lineage- and species-specific aggregation fidelity was
      only detected in 8% (4 out of 48) of the aggregation fidelity assays run. These
      results indicate that under laboratory conditions, host-associated lineages of
      bed bugs are reproductively compatible, and aggregation pheromones are not
      capable of preventing gene flow between lineages.

PMID- 29030575
TI  - Adolescent Ethanol Exposure Enhances NMDA Receptor-Mediated Currents in
      Hippocampal Neurons: Reversal by Gabapentin.
AB  - Adolescent intermittent ethanol (AIE) exposure compromises neural function into
      adulthood. We have reported that astrocyte-secreted thrombospondins, and their
      target neuronal receptors (alpha2delta-1) are upregulated in the hippocampus in
      adulthood after AIE, suggesting aberrant excitatory synaptogenesis and
      hyperexcitability in memory-related circuits. Gabapentin antagonizes the
      interaction of thrombospondins (TSPs) with the alpha2delta-1 receptor, and thus
      may reverse or ameliorate the effects of AIE on hippocampal function. Adolescent
      rats were exposed to AIE or vehicle. In adulthood, hippocampal slices were
      prepared. Half of the slices from each animal were pre-incubated in normal
      artificial cerebrospinal fluid (aCSF) while half were pre-incubated in aCSF
      containing gabapentin. Whole-cell voltage clamp recordings were then made from
      CA1 pyramidal cells in normal aCSF. Evoked, N-methyl-D-aspartate (NMDA) receptor
      mediated currents were recorded at baseline, and after application of the GluN2B
      antagonist, RO25-6981. Current amplitudes were higher in neurons from AIE-exposed
      animals. However, no amplitude increase was observed in neurons from slices that
      had been pre-incubation in gabapentin. GluN2B antagonism reduced NMDA receptor
      mediated currents more efficaciously in cells from AIE-exposed animals, an effect
      that was also reversed by pre-incubation in gabapentin. These findings identify a
      mechanism underlying the enduring effects of AIE, and a clinically-utilized agent
      that may ameliorate those effects.

PMID- 29030576
TI  - Genetic induction of hypometabolism by ablation of MC4R does not suppress ALS
      like phenotypes in the G93A mutant SOD1 mouse model.
AB  - Dysfunction and death of motor neurons leads to progressive paralysis in
      amyotrophic lateral sclerosis (ALS). Recent studies have reported organism-level
      metabolic dysfunction as a prominent but poorly understood feature of the
      disease. ALS patients are hypermetabolic with increased resting energy
      expenditure, but if and how hypermetabolism contributes to disease pathology is
      unknown. We asked if decreasing metabolism in the mutant superoxide dismutase 1
      (SOD1) mouse model of ALS (G93A SOD1) would alter motor function and survival. To
      address this, we generated mice with the G93A SOD1 mutation that also lacked the
      melanocortin-4 receptor (MC4R). MC4R is a critical regulator of energy
      homeostasis and food intake in the hypothalamus. Loss of MC4R is known to induce
      hyperphagia and hypometabolism in mice. In the MC4R null background, G93A SOD1
      mice become markedly hypometabolic, overweight and less active. Decreased
      metabolic rate, however, did not reverse any ALS-related disease phenotypes such
      as motor dysfunction or decreased lifespan. While hypermetabolism remains an
      intriguing target for intervention in ALS patients and disease models, our data
      indicate that the melanocortin system is not a good target for manipulation.
      Investigating other pathways may reveal optimal targets for addressing metabolic
      dysfunction in ALS.

PMID- 29030577
TI  - Population admixture in Chinese and European Sus scrofa.
AB  - Relationships between different populations were investigated using Porcine 60 K
      data from 1,135 domestic pigs and wild boars across Europe and China. The results
      indicate that most European breeds have been introgressed with Chinese ancestry,
      but the extent of introgression varies considerably among breeds. Moreover, the
      main source of this introgression is pigs from South China, closely related to
      Bamaxiang and Dongshan pigs. Contributions from East and Central Chinese pig
      breeds are also detectable. Phylogeny reconstruction places European wild boars
      among European domestic breeds. Coalescent simulations indicate that this may be
      the result of gene flow from European wild boars to European domestic pigs. These
      results will facilitate further genomic studies such as genome-wide association
      studies, selection signature detection and genomic prediction.

PMID- 29030578
TI  - Simultaneous fusion, imaging and encryption of multiple objects using a single
      pixel detector.
AB  - A novel technique for the simultaneous fusion, imaging and encryption of multiple
      objects using a single-pixel detector is proposed. Here, encoded multiplexing
      patterns are employed to illuminate multiple objects simultaneously. The mixed
      light reflected from the objects is detected by a single-pixel detector. An
      iterative reconstruction method is used to restore the fused image by summing the
      multiplexed patterns and detected intensities. Next, clear images of the objects
      are recovered by decoding the fused image. We experimentally obtain fused and
      multiple clear images by utilizing a single-pixel detector to collect the direct
      and indirect reflected light. Technically, by utilizing the patterns with per
      pixel exposure control, multiple objects' information is multiplexed into the
      detected intensities and then demultiplexed computationally under the single
      pixel imaging and compressed sensing schemes. An encryption experiment is
      performed by setting the multiplexed patterns' encoding as keys.

PMID- 29030579
TI  - Effect of iodinated contrast media on renal perfusion: A randomized comparison
      study in pigs using quantitative contrast-enhanced ultrasound (CEUS).
AB  - The administration of iodinated contrast media (CM) can cause microcirculatory
      disorder leading to acute renal dysfunction. In a prospective, randomized
      investigation two CM (Iodixanol vs Iopromide) were compared in 16 pigs. Each
      animal received 10 intra-aortal injections (5 ml Iodixanol or 4.32 ml Iopromide).
      Microcirculation was assessed using contrast-enhanced ultrasound (CEUS) directly
      on the kidney surface using time-to-peak (TTP) and blood-volume-analysis.
      Macroscopic observations were documented. Post mortem residual CM distribution in
      the kidneys was detected using X-ray. TTP was significantly prolonged over the
      descending vasa recta of the Iopromide group. This coincided with a visible
      marble-like pattern on the kidney surface occurring in 30 out of 80 Iopromide
      injections but in 4 out of 80 Iodixanol-injections (p = 0.007). The blood volume
      over the entire kidney did not change after Iodixanol-application, but decreased
      by about 6.1% after Iopromide-application. The regional blood volume in the renal
      cortex showed a tendency to decrease by about 13.5% (p = 0.094) after Iodixanol
      application, and clearly decreased by about 31.7% (p = 0.022) after Iopromide
      application. The study revealed a consistent influence of repeated injections of
      two different CM on the kidney perfusion using three different imaging methods
      (CEUS analysis, macroscopic observation and X-ray analysis).

PMID- 29030580
TI  - Bony labyrinth morphology clarifies the origin and evolution of deer.
AB  - Deer are an iconic group of large mammals that originated in the Early Miocene of
      Eurasia (ca. 19 Ma). While there is some consensus on key relationships among
      their members, on the basis of molecular- or morphology-based analyses, or
      combined approaches, many questions remain, and the bony labyrinth has shown
      considerable potential for the phylogenetics of this and other groups. Here we
      examine its shape in 29 species of living and fossil deer using 3D geometric
      morphometrics and cladistics. We clarify several issues of the origin and
      evolution of cervids. Our results give new age estimates at different nodes of
      the tree and provide for the first time a clear distinction of stem and crown
      Cervidae. We unambiguously attribute the fossil Euprox furcatus (13.8 Ma) to
      crown Cervidae, pushing back the origin of crown deer to (at least) 4 Ma.
      Furthermore, we show that Capreolinae are more variable in bony labyrinth shape
      than Cervinae and confirm for the first time the monophyly of the Old World
      Capreolinae (including the Chinese water deer Hydropotes) based on morphological
      characters only. Finally, we provide evidence to support the sister group
      relationship of Megaloceros giganteus with the fallow deer Dama.

PMID- 29030581
TI  - Dielectric imaging for differentiation between cancer and inflammation in vivo.
AB  - In this study, we develop an in vivo dielectric imaging technique that measures
      capacitance using pin-type electrode arrays. Compared to normal tissues, cancer
      tissues exhibit higher capacitance values, allowing us to image the cancer region
      and monitor the chemotherapeutic effects of cancer in real-time. A comparison
      with the histopathological results shows that the in vivo dielectric imaging
      technique is able to detect small tumors (<3 mm) and tumor-associated changes. In
      addition, we demonstrate that cancer and inflammation may be distinguished by
      measuring the capacitance images at different frequencies. In contrast, the
      positron emission tomography using 2-[18F]-fluoro-2-deoxy-D-glucose was not
      capable of discriminating between cancer and inflammation.

PMID- 29030582
TI  - Non-contact method to freely control the radiation patterns of antenna with multi
      folded transformation optics.
AB  - In this paper, we propose to use multi-folded transformation optics method to
      design a non-contact illusion device that can distantly and freely manipulate the
      radiation behavior of antenna located at a certain distance and such manipulation
      is enabled by the use of mapped electromagnetic medium coated with the
      transformed medium. The proposed design aims to achieve the radiation pattern of
      our choice from the antenna that does not possess any electromagnetic medium.
      Based on this, the functionality of parabolic antenna is distantly achieved from
      the point source. We further extended our idea to array of antennas in which the
      proposed device distantly makes the linear array of antennas behave like a
      geometrically different array of antennas. Our work extends the concept of
      illusion optics for active scatterer that will be very helpful for future antenna
      design.

PMID- 29030583
TI  - Catastrophic failure of nacre under pure shear stresses of torsion.
AB  - Nacre, a composite made from biogenic aragonite and proteins, exhibits excellent
      strength and toughness. Here, we show that nacreous sections can exhibit complete
      brittle fracture along the tablet interfaces at the proportional limit under pure
      shear stresses of torsion. We quantitatively separate the initial tablet sliding
      primarily resisted by nanoscale aragonite pillars from the following sliding
      resisted by various microscale toughening mechanisms. We postulate that the
      ductility of nacre can be limited by eliminating tablet interactions during crack
      propagations. Our findings should help pursuing further insights of layered
      materials by using torsion.

PMID- 29030584
TI  - Brain activity to transitional objects in patients with borderline personality
      disorder.
AB  - Adult patients with borderline personality disorders (BPD) frequently have
      attachments to inanimate transitional objects (TOs) such as stuffed animals.
      Using event-related potential (ERP) recordings, we determined in patients with
      BPD the neural correlates of the processing of these attachment-relevant objects
      and their functional significance. Sixteen female patients with BPD viewed
      pictures of their TOs, other familiar stuffed toys (familiar objects, FOs), and
      unfamiliar objects (UOs). ERPs in the patients were compared to those in 16
      matched healthy controls who possessed a stuffed animal of comparably high
      familiarity. Here, we found a specific increase of frontal P3/LPP amplitude in
      patients with BPD, which was related to attachment anxiety and depression scores.
      Attachment-related TO stimuli in patients with BPD specifically modulated stages
      of emotional stimulus evaluation reflecting processing of self-relevance. The
      relation of the frontal ERP effect to patients' attachment anxiety and depression
      highlights the function of TOs for coping with anxiety about being abandoned by
      significant others and for dealing with depressive symptoms.

PMID- 29030585
TI  - Environmental controls on sap flow in black locust forest in Loess Plateau,
      China.
AB  - Black locust accounts for over 90% of artificial forests in China's Loess Plateau
      region. However, water use of black locust is an uphill challenge for this semi
      arid region. To accurately quantify tree water use and to explain the related
      hydrological processes, it is important to collect reliable data for application
      in the estimation of sap flow and its response to environmental factors. This
      study measured sap flow in black locust in the 2015 and 2016 growth seasons using
      the thermal dissipation probes technique and laboratory-calibrated Granier's
      equation. The study showed that the laboratory calibrated coefficient alpha was
      much larger than the original value presented by Granier, while the coefficient
      beta was similar to the original one. The average daily transpiration was 2.1 mm
      day-1 for 2015 and 1.6 mm day-1 for 2016. Net solar radiation (Rn) was the key
      meteorological factor controlling sap flow, followed by vapor pressure deficit
      (VPD) and then temperature (T). VPD had a threshold control on sap flow at
      threshold values of 1.9 kPa for 2015 and 1.6 kPa for 2016. The effects of diurnal
      hysteresis of Rn, VPD and T on sap flow were evident, indicating that black
      locust water use was conservative.

PMID- 29030586
TI  - Batrachochytrium salamandrivorans not detected in U.S. survey of pet salamanders.
AB  - We engaged pet salamander owners in the United States to screen their animals for
      two amphibian chytrid fungal pathogens Batrachochytrium dendrobatidis (Bd) and B.
      salamandrivorans (Bsal). We provided pet owners with a sampling kit and
      instructional video to swab the skin of their animals. We received 639 salamander
      samples from 65 species by mail, and tested them for Bd and Bsal using qPCR. We
      detected Bd on 1.3% of salamanders (95% CI 0.0053-0.0267) and did not detect Bsal
      (95% CI 0.0000-0.0071). If Bsal is present in the U.S. population of pet
      salamanders, it occurs at a very low prevalence. The United States Fish and
      Wildlife Service listed 201 species of salamanders as "injurious wildlife" under
      the Lacey Act (18 U.S.C. S 42) on January 28, 2016, a precautionary action to
      prevent the introduction of Bsal to the U.S. through the importation of
      salamanders. This action reduced the number of salamanders imported to the U.S.
      from 2015 to 2016 by 98.4%. Our results indicate that continued precautions
      should be taken to prevent the introduction and establishment of Bsal in the
      U.S., which is a hotspot of salamander biodiversity.

PMID- 29030587
TI  - NatD promotes lung cancer progression by preventing histone H4 serine
      phosphorylation to activate Slug expression.
AB  - N-alpha-acetyltransferase D (NatD) mediates N-alpha-terminal acetylation (Nt
      acetylation) of histone H4 known to be involved in cell growth. Here we report
      that NatD promotes the migratory and invasive capabilities of lung cancer cells
      in vitro and in vivo. Depletion of NatD suppresses the epithelial-to-mesenchymal
      transition (EMT) of lung cancer cells by directly repressing the expression of
      transcription factor Slug, a key regulator of EMT. We found that Nt-acetylation
      of histone H4 antagonizes histone H4 serine 1 phosphorylation (H4S1ph), and that
      downregulation of Nt-acetylation of histone H4 facilitates CK2alpha binding to
      histone H4 in lung cancer cells, resulting in increased H4S1ph and epigenetic
      reprogramming to suppress Slug transcription to inhibit EMT. Importantly, NatD is
      commonly upregulated in primary human lung cancer tissues where its expression
      level correlates with Slug expression, enhanced invasiveness, and poor clinical
      outcomes. These findings indicate that NatD is a crucial epigenetic modulator of
      cell invasion during lung cancer progression.NatD is an acetyltransferase
      responsible for N-alpha-terminal acetylation of the histone H4 and H2A and has
      been linked to cell growth. Here the authors show that NatD-mediated acetylation
      of histone H4 serine 1 competes with the phosphorylation by CK2alpha at the same
      residue thus leading to the upregulation of Slug and tumor progression.

PMID- 29030588
TI  - Impaired branched-chain amino acid metabolism may underlie the nonalcoholic fatty
      liver disease-like pathology of neonatal testosterone-treated female rats.
AB  - Polycystic ovary syndrome (PCOS) is frequently associated with non-alcoholic
      fatty liver disease (NAFLD), but the mechanisms involved in the development of
      NAFLD in PCOS are not well known. We investigated histological changes and
      metabolomic profile in the liver of rat models of PCOS phenotype induced by
      testosterone or estradiol. Two-day old female rats received sc injections of 1.25
      mg testosterone propionate (Testos; n = 10), 0.5 mg estradiol benzoate (E2; n =
      10), or vehicle (control group, CNT; n = 10). Animals were euthanized at 90-94 d
      of age and the liver was harvested for histological and metabolomic analyses.
      Findings showed only Testos group exhibited fatty liver morphology and higher
      levels of ketogenic and branched-chain amino acids (BCAA). Enrichment analysis
      showed effects of testosterone on BCAA degradation pathway and mitochondrial
      enzymes related to BCAA metabolism. Testos group also had a decreased liver fatty
      acid elongase 2 (ELOVL2) activity. E2 group had reduced lipid and acylcarnitine
      metabolites in the liver. Both groups had increased organic cation transporters
      (SLC22A4 and SLC16A9) activity. These findings indicate that neonatal
      testosterone treatment, but not estradiol, produces histological changes in
      female rat liver that mimic NAFLD with testosterone-treated rats showing impaired
      BCAA metabolism and dysfunctions in ELOVL2, SLC22A4 and SLC16A9 activity.

PMID- 29030589
TI  - Aberrant ocular architecture and function in patients with Klinefelter syndrome.
AB  - Klinefelter Syndrome (KS), the most common chromosomal disorder in men (47,XXY),
      is associated with numerous comorbidities. Based on a number of isolated case
      reports, we performed the first systematic and comprehensive evaluation of eye
      health in KS patients with a focus on ocular structure and vascularization.
      Twenty-one KS patients and 26 male and 38 female controls underwent a variety of
      non-invasive examinations investigating ocular morphology (examination of retinal
      thickness, optic nerve head, and cornea) and function (visual field testing and
      quantification of ocular vessel density by optical coherence tomography
      angiography). In comparison to healthy controls, KS patients exhibited a smaller
      foveal avascular zone and a decreased retinal thickness due to a drastically
      thinner outer nuclear layer. The cornea of KS patients showed a decreased
      peripheral thickness and volume. In perimetry evaluation, KS patients required
      brighter stimuli and gave more irregular values. KS patients show an ocular
      phenotype including morphological and functional features, which is very likely
      caused by the supernumerary X chromosome. Thus, KS should not be limited to
      infertility, endocrine dysfunction, neurocognitive and psychosocial
      comorbidities. Defining an aberrant ocular morphology and function, awareness for
      possible eye problems should be raised.

PMID- 29030590
TI  - Cytotoxicity of thymoquinone alone or in combination with cisplatin (CDDP)
      against oral squamous cell carcinoma in vitro.
AB  - Cisplatin (CDDP) is potent anticancer agent used for several tumor types.
      Thymoquinone (TQ) is naturally occurring compound drawing great attention as
      anticancer and chemomodulator for chemotherapies. Herein, we studied the
      potential cytotoxicity of thymoquinone, CDDP and their combination against human
      oral squamous cell carcinoma cell in contrast to normal oral epithelial cells.
      CDDP similarly killed both head and neck squamous cell carcinoma cells (UMSCC
      14C) and normal oral epithelial cells (OEC). TQ alone exerted considerable
      cytotoxicity against UMSCC-14C cells; while it induced weaker killing effect
      against normal oral epithelial cells (OEC). Equitoxic combination of TQ and CDDP
      showed additive to synergistic interaction against both UMSCC-14C and OEC cells.
      TQ alone increased apoptotic cell fraction in UMSCC-14C cells, as early as after
      6 hours. In addition, prolonged exposure of UMSCC-14C to TQ alone resulted in
      96.7 +/- 1.6% total apoptosis which was increased after combination with CDDP to
      99.3 +/- 1.2% in UMSCC-14C cells. On the other hand, TQ induced marginal increase
      in the apoptosis in OEC and even decreased the apoptosis induced by CDDP alone.
      Finally, apoptosis induction results were confirmed by the change in the
      expression levels of p53, Bcl-2 and Caspase-9 proteins in both UMSCC-14c and OEC
      cells.

PMID- 29030591
TI  - Enhanced terahertz fingerprint detection with ultrahigh sensitivity using the
      cavity defect modes.
AB  - We report a new scheme of realizing terahertz fingerprint detection with
      ultrahigh sensitivity. Instead of using the direct absorption of terahertz
      through a bare sample in the regular transmission scheme, a cavity mode
      resonating at the characteristic frequency of the sample is used and due to the
      high dependence of the cavity mode transmission on the material loss, an
      amplified transmission decaying is observed when the sample is loaded into the
      cavity. Furthermore, this scheme retains the feature of substance identification.
      A one-dimensional photonic crystal cavity is used as the example for the
      detection of alpha-lactose and an efficient detection of 10 nm alpha-lactose can
      be achieved, which corresponds to 1/57000 of the free space wavelength at the
      characteristic frequency of 0.529 THz, exhibiting a sensitivity over 400 times
      higher than the regular transmission method.

PMID- 29030592
TI  - Rare occurrence of inflammatory bowel disease in a cohort of Han Chinese
      ankylosing spondylitis patients- a single institute study.
AB  - Despite a high prevalence of ankylosing spondylitis (AS) in Han Chinese, the
      clinical experience remains very limited in the extra-articular presentation of
      inflammatory bowel disease (IBD). A monocentric retrospective study was performed
      for the AS-associated IBD manifestation. This study analyzed AS patients
      fulfilling the 1984 revised New York diagnostic criteria, excluding those who had
      the onset of IBD before or concurrently with the diagnosis of AS, for their
      demographic, clinical, laboratory, radiological, pathological and medication
      data, particularly in the usage of anti-TNF monoclonal antibody. Among 988 AS
      patients with 19.8% female, 4 (0.4%) had the overt IBD presentation, one female
      and 3 male aged 28 to 47 years (38.8 +/- 4.6), all ulcerative colitis with the
      characteristic histopathological findings. At the onset of colitis, all had a
      long-term disease duration of 10 to 25 years (17.5 +/- 6.5) and high BASDAI 7.5
      to 8.8 (8.2 +/- 0.5) with the hip joint involvement. There were recurrent flares
      of colitis despite the treatment with corticosteroids and
      messalazopyrin/salazopyrin, and no relapses of IBD were observed for 6.0 +/- 1.1
      years after the adalimumab (ADA) therapy. In this retrospective cohort, we
      demonstrate the rarity of AS-associated IBD manifestation in Han Chinese with a
      beneficent effect from the ADA therapy.

PMID- 29030593
TI  - Fish perform like mammals and birds in inhibitory motor control tasks.
AB  - Inhibitory control is an executive function that positively predicts performance
      in several cognitive tasks and has been considered typical of vertebrates with
      large and complex nervous systems such as primates. However, evidence is growing
      that some fish species have evolved complex cognitive abilities in spite of their
      relatively small brain size. We tested whether fish might also show enhanced
      inhibitory control by subjecting guppies, Poecilia reticulata, to the motor task
      used to test warm-blooded vertebrates. Guppies were trained to enter a horizontal
      opaque cylinder to reach a food reward; then, the cylinder was replaced by a
      transparent one, and subjects needed to inhibit the response to pass thought the
      transparency to reach the food. Guppies performed correctly in 58% trials, a
      performance fully comparable to that observed in most birds and mammals. In
      experiment 2, we tested guppies in a task with a different type of reward, a
      group of conspecifics. Guppies rapidly learned to detour a transparent barrier to
      reach the social reward with a performance close to that of experiment 1. Our
      study suggests that efficient inhibitory control is shown also by fish, and that
      its variation between-species is only partially explained by variation in brain
      size.

PMID- 29030594
TI  - Pollinator-mediated selection on flowering phenology and floral display in a
      distylous herb Primula alpicola.
AB  - The targets and causes of phenotypic selection are crucial to understanding
      evolutionary ecology. However, few studies have examined selection quantitatively
      from multiple sources on the same trait identified the agent of natural selection
      experimentally. Here we quantified phenotypic selection on traits, including
      flowering phenology and aspects of floral display via female fitness, in the
      distylous perennial herb Primula alpicola. To determine the role of pollinators
      in generating selection effects on floral traits, we compared the phenotypic
      selection gradients in open-pollinated and hand-pollinated plants. Our results
      show that pollinator-mediated linear selection on flowering start and
      correlational selection on the number of flowers and scape height explains most
      of the net phenotypic selection on these traits suggesting pollinators played an
      important role in shaping floral diversity. We used path analysis and structural
      equation modeling (SEM) to examine how herbivores affected the relationship
      between floral traits and female fitness, but no significant selection was caused
      by seed predators. These results suggest pollinators, not herbivores maybe the
      significant agent of selection on flora traits.

PMID- 29030595
TI  - Correlation between the Arrhenius crossover and the glass forming ability in
      metallic glasses.
AB  - The distinctive characteristic of the metallic glass-forming system is that the
      variation in viscosity with temperature obeys Vogel-Fulcher-Tammann (VFT)
      relationship in the undercooled state and Arrhenius relationship in the high
      temperature region. A dimensionless index has thus been proposed based on the
      Arrhenius-VFT crossover and the classical nucleation rate and growth rate theory
      to evaluate the glass-forming ability (GFA). The indicator G(a) is expressed with
      the combination of T g , the glass transition temperature, T x , the onset
      crystallization temperature, T l , the liquidus temperature, T 0, the VFT
      temperature, and a a constant that could be determined according to the best
      correlation between G(a) and the critical cooling rate (R c ). Compared with
      other GFA indexes, G(a) shows the best fit with R c , with the square of the
      correlation coefficient (R 2) being 0.9238 when a = 0.15 for the 23 various alloy
      systems concerned about. Our results indicate the crossover in the viscosity
      variation has key effect on GFA and one can use the index G(a) to predict R c and
      GFA for different alloys effectively.

PMID- 29030596
TI  - Mesenchymal stem cells from tumor microenvironment favour breast cancer stem cell
      proliferation, cancerogenic and metastatic potential, via ionotropic purinergic
      signalling.
AB  - Interaction between tumor cells and the microenvironment is key in initiation,
      progression, and invasiveness of cancer. In particular, mesenchymal stem cells
      (MSCs) are recruited to the sites of developing tumors, thus promoting metastasis
      formation. Although it is well known that MSCs migrate and integrate in the tumor
      microenvironment (TME), their fate and function inside the tumor is still not
      clear. In this study, we analyzed the role played by MSCs in breast cancer
      oncogenesis. Data indicate that interaction of breast cancer cells with MSCs
      results in an increased proliferation and metabolic activity of breast cancer
      cells, partially due to MSC-derived microvesicles that are shed in the TME.
      Moreover, we addressed the question of whether we could modulate such interaction
      by acting on P2X-mediated intercellular communication. By inhibiting P2X-mediated
      purinergic signaling, we succeeded in reducing both the cancerogenic as well as
      the metastatic potential of breast cancer cells co-cultured with MSCs, in 2D as
      well as in 3D in vitro models. Data obtained demonstrate for the first time that
      the trophic effect of MSCs on breast cancer cell growth is exerted via ionotropic
      purinergic signaling, thus suggesting the inhibition of the purinergic signaling
      system as a potential target for therapeutic intervention.

PMID- 29030597
TI  - Stabilization of a bat-pitcher plant mutualism.
AB  - Despite the long persistence of many mutualisms, it is largely unknown which
      mechanisms stabilize these interactions. This is especially true if only one
      mutualism partner can choose alternative partners while the other cannot,
      resulting in a power asymmetry. According to biological market theory the
      choosing partner should prefer the more dependent partner if the latter offers
      commodities of higher quality than its competitors. We tested this prediction
      using Bornean carnivorous pitcher plants (Nepenthes hemsleyana) that strongly
      rely on faecal nitrogen of bats (Kerivoula hardwickii) which roost inside the
      pitchers. The bats also roost in furled leaves of various plants. Surprisingly,
      during field observations the bats did not always choose N. hemsleyana pitchers
      despite their superior quality but were generally faithful either to pitchers or
      to furled leaves. In behavioural experiments 21% of the leaf-roosting bats
      switched to pitchers, while the majority of these bats and all pitcher-roosting
      individuals were faithful to the roost type in which we had found them. Genetic
      differentiation cannot explain this faithfulness, which likely results from
      different roosting traditions. Such traditions could have stabilizing or
      destabilizing effects on various mutualisms and should be investigated in more
      detail.

PMID- 29030598
TI  - Single nucleotide polymorphisms in the ETS1 gene are associated with idiopathic
      inflammatory myopathies in a northern Chinese Han population.
AB  - Single-nucleotide polymorphisms (SNPs) in the ETS1 gene are associated with
      several auto-inflammatory diseases. In this study, we determined whether ETS1
      gene polymorphisms confer susceptibility to idiopathic inflammatory myopathies
      (IIMs) in a northern Chinese Han population. DNA samples were collected from 1017
      IIM patients: 363 PM cases and 654 DM cases. The results were compared with those
      of 1280 healthy controls. Five SNPs in the ETS1 region (rs7117932, rs6590330,
      rs4937362, rs10893845 and rs1128334) were assessed and genotyped using the
      Sequenom platform. Our data indicated that the rs7117932 alleles and genotypes
      are associated with DM and IIMs (P c  = 6.0 * 10-3 and P c  = 0.029; P c  = 0.013
      and P c  = 0.019, respectively). We found a significantly greater percentage of
      DM and IIM patients with an A allele of rs6590330 than that in the control
      population (P c  = 0.033 and P c  = 0.013). Additionally, the rs6590330 genotype
      was associated with IIMs (P c  = 0.020). The percentages of rs7117932 and
      rs6590330 SNPs were significantly greater in DM and IIM patients with
      interstitial lung disease (ILD) (all P c  < 0.05). This is the first study to
      reveal that ETS1 polymorphisms are associated with IIMs alone and IIMs with ILD
      in a northern Chinese Han population.

PMID- 29030600
TI  - High-speed spinning disks on flexible threads.
AB  - A common spinning toy, called "buzzer", consists of a perforated disk and
      flexible threads. Despite of its simple construction, a buzzer can effectively
      transfer translational motions into high-speed rotations. In the present work, we
      find that the disk can be spun by hand at an extremely high rotational speed,
      e.g., 200,000 rpm, which is much faster than the previously reported speed of any
      manually operated device. We explore, both experimentally and theoretically, the
      detailed mechanics and potential applications of such a thread-disk system. The
      theoretical prediction, validated by experimental measurements, can help design
      and optimize the system for, e.g., easier operation and faster rotation.
      Furthermore, we investigate the synchronized motion of multiple disks spinning on
      a string. Distinctly different twist waves can be realized by the multi-disk
      system, which could be exploited in the control of mechanical waves. Finally, we
      develop two types of manually-powered electric generators based on the thread
      disk system. The high-speed rotation of the rotors enables a pulsed high current,
      which holds great promise for potential applications in, for instance, generating
      electricity and harvesting energy from ocean waves and other rhythmic
      translational motions.

PMID- 29030601
TI  - Interfering with the high-affinity interaction between wheat amylase trypsin
      inhibitor CM3 and toll-like receptor 4: in silico and biosensor-based studies.
AB  - Wheat amylase/trypsin bi-functional inhibitors (ATIs) are protein stimulators of
      innate immune response, with a recently established role in promoting both
      gastrointestinal and extra-gastrointestinal inflammatory syndromes. These
      proteins have been reported to trigger downstream intestinal inflammation upon
      activation of TLR4, a member of the Toll-like family of proteins that activates
      signalling pathways and induces the expression of immune and pro-inflammatory
      genes. In this study, we demonstrated the ability of ATI to directly interact
      with TLR4 with nanomolar affinity, and we kinetically and structurally
      characterized the interaction between these macromolecules by means of a
      concerted approach based on surface plasmon resonance binding analyses and
      computational studies. On the strength of these results, we designed an
      oligopeptide capable of preventing the formation of the complex between ATI and
      the receptor.

PMID- 29030602
TI  - Oscillatory electrostatic potential on graphene induced by group IV element
      decoration.
AB  - The structures and electronic properties of partial C, Si and Ge decorated
      graphene were investigated by first-principles calculations. The calculations
      show that the interaction between graphene and the decoration patches is weak and
      the semiconductor patches act as agents for weak electron doping without much
      disturbing graphene electronic pi-bands. Redistribution of electrons due to the
      partial decoration causes the electrostatic potential lower in the decorated
      graphene areas, thus induced an electric field across the boundary between the
      decorated and non-decorated domains. Such an alternating electric field can
      change normal stochastic adatom diffusion to biased diffusion, leading to
      selective mass transport.

PMID- 29030603
TI  - Conjugation with L,L-diphenylalanine Self-Assemblies Enhances In Vitro Antitumor
      Activity of Phthalocyanine Photosensitizer.
AB  - We present the synthesis and characterization of new peptide conjugates obtained
      by hierarchical co-assembly of L,L-diphenylalanine (FF) and zinc phthalocyanine
      complexes (ZnPc) in water. Self-assembly capabilities under defined conditions
      were investigated by scanning electron microscopy, and photophysical properties
      were evaluated using UV-Vis and fluorescence spectroscopy. AFM observations
      demonstrated that these ZnPcs form different highly ordered arrays on the
      crystalline faces of the FF microplates and that surface roughness significantly
      changes with the presence of differently substituted phthalocyanine units. XRD
      assays showed that the overall molecular packing of the conjugates is organized
      according to a hexagonal symmetry, with ZnPcs hosted in the interstices of the
      peptide phase. In vitro photodynamic studies were conducted on human breast
      cancer MCF-7 cells to investigate both cellular uptake and cytotoxicity. It was
      shown that FF self-assemblies are not toxicity and enhance accumulation of ZnPc
      in MCF-7 cells, improving apoptotic cell death upon irradiation. Our findings
      demonstrate enhancement of ZnPc antitumor efficiency by FF conjugates and a proof
      of-concept for new photosensitizer carriers based on peptide conjugates.

PMID- 29030599
TI  - Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors
      with human longevity.
AB  - Genomic analysis of longevity offers the potential to illuminate the biology of
      human aging. Here, using genome-wide association meta-analysis of 606,059
      parents' survival, we discover two regions associated with longevity (HLA
      DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5,
      CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up
      smoking, educational attainment, openness to new experience and high-density
      lipoprotein (HDL) cholesterol levels are most positively genetically correlated
      with lifespan while susceptibility to coronary artery disease (CAD), cigarettes
      smoked per day, lung cancer, insulin resistance and body fat are most negatively
      correlated. We suggest that the effect of education on lifespan is principally
      mediated through smoking while the effect of obesity appears to act via CAD.
      Using instrumental variables, we suggest that an increase of one body mass index
      unit reduces lifespan by 7 months while 1 year of education adds 11 months to
      expected lifespan.Variability in human longevity is genetically influenced. Using
      genetic data of parental lifespan, the authors identify associations at HLA
      DQA/DRB1 and LPA and find that genetic variants that increase educational
      attainment have a positive effect on lifespan whereas increasing BMI negatively
      affects lifespan.

PMID- 29030604
TI  - Flexible Semiconductor Technologies with Nanoholes-Provided High Areal Coverages
      and Their Application in Plasmonic-Enhanced Thin Film Photovoltaics.
AB  - Mechanical flexibility and advanced light management have gained great attentions
      in designing high performance, flexible thin film photovoltaics for the
      realization of building-integrated optoelectronic devices and portable energy
      sources. This study develops a soft thermal nanoimprint process for fabricating
      nanostructure decorated substrates integrated with amorphous silicon solar cells.
      Amorphous silicon (a-Si:H) solar cells have been constructed on nanoholes array
      textured polyimide (PI) substrates. It has been demonstrated that the
      nanostructures not only are beneficial to the mechanical flexibility improvement
      but also contribute to sunlight harvesting enhancement. The a-Si:H solar cells
      constructed on such nanopatterned substrates possess broadband-enhanced light
      absorption, high quantum efficiency and desirable power conversion efficiency
      (PCE) and still experience minimal PCE loss even bending around 180 degrees . The
      PCE performance without antireflection coatings increases to 7.70% and it
      improves 40% compared with the planar devices. Although the advantages and
      feasibility of the schemes are demonstrated only in the application of a-Si:H
      solar cells, the ideas are able to extend to applications of other thin film
      photovoltaics and semiconductor devices.

PMID- 29030605
TI  - Cubic gauche polymeric nitrogen under ambient conditions.
AB  - The long-sought cubic gauche phase of polymeric nitrogen (cg-PN) with nitrogen
      nitrogen single bonds has been synthesized together with a related phase by a
      radio-frequency plasma reaction under near-ambient conditions. Here, we report
      the synthesis of polymeric nitrogen using a mixture of nitrogen and argon flowing
      over bulk beta-sodium azide or beta-sodium azide dispersed on 100 nm long
      multiwall carbon nanotubes. The cg-PN phase is identified by Raman and attenuated
      total reflection-Fourier transform infrared spectroscopy, and powder X-ray
      diffraction. The synthesis of the cubic gauche allotrope of high energy density
      polymeric nitrogen under near-ambient conditions should therefore enable its
      optimized production and applications as a "green" energetic material and a
      potential catalyst for different chemical reactions.Polymeric phases of nitrogen
      are promising as environmentally-friendly, high energy-density materials, but are
      inherently unstable. Here, the authors report the synthesis and stabilization of
      polymeric nitrogen in its cubic gauche phase under near-ambient conditions, via
      plasma-enhanced chemical vapour deposition.

PMID- 29030606
TI  - Molecular mechanism of synergy between the antimicrobial peptides PGLa and
      magainin 2.
AB  - PGLa and magainin 2 (MAG2) are amphiphilic alpha-helical membranolytic peptides
      from frog skin with known synergistic antimicrobial activity. By systematically
      mutating residues in the two peptides it was possible to identify the ones
      crucial for the synergy, as monitored by biological assays, fluorescence vesicle
      leakage, and solid-state 15N-NMR. Electrostatic interactions between anionic
      groups in MAG2 and cationic residues in PGLa enhance synergy but are not
      necessary for the synergistic effect. Instead, two Gly residues (7 and 11) in a
      so-called GxxxG motif in PGLa are necessary for synergy. Replacing either of them
      with Ala or another hydrophobic residue completely abolishes synergy according to
      all three methods used. The designer-made peptide MSI-103, which has a similar
      sequence as PGLa, shows no synergy with MAG2, but by introducing two Gly
      mutations it was possible to make it synergistic. A molecular model is proposed
      for the functionally active PGLa-MAG2 complex, consisting of a membrane-spanning
      antiparallel PGLa dimer that is stabilized by intimate Gly-Gly contacts, and
      where each PGLa monomer is in contact with one MAG2 molecule at its C-terminus.

PMID- 29030607
TI  - CCDC88B is required for pathogenesis of inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) involves interaction between host genetic
      factors and environmental triggers. CCDC88B maps within one IBD risk locus on
      human chromosome 11q13. Here we show that CCDC88B protein increases in the colon
      during intestinal injury, concomitant with an influx of CCDC88B+lymphoid and
      myeloid cells. Loss of Ccdc88b protects against DSS-induced colitis, with fewer
      pathological lesions and reduced intestinal inflammation in Ccdc88b-deficient
      mice. In a T cell transfer model of colitis, Ccdc88b mutant CD4+ T cells do not
      induce colitis in immunocompromised hosts. Expression of human CCDC88B RNA and
      protein is higher in IBD patient colons than in control colon tissue. In human
      CD14+ myeloid cells, CCDC88B is regulated by cis-acting variants. In a cohort of
      patients with Crohn's disease, CCDC88B expression correlates positively with
      disease risk. These findings suggest that CCDC88B has a critical function in
      colon inflammation and the pathogenesis of IBD.Hook-related protein family member
      CCDC88b is encoded by a locus that has been associated with inflammatory bowel
      disease. Here the authors show that Ccdc88b inactivation in T cells prevents
      colitis in a transfer model, and detect high colonic levels of CCDC88b in
      patients with Crohn disease or ulcerative colitis, identifying that expression
      correlates with disease risk.

PMID- 29030608
TI  - Self-organisation of small-world networks by adaptive rewiring in response to
      graph diffusion.
AB  - Complex networks emerging in natural and human-made systems tend to assume small
      world structure. Is there a common mechanism underlying their self-organisation?
      Our computational simulations show that network diffusion (traffic flow or
      information transfer) steers network evolution towards emergence of complex
      network structures. The emergence is effectuated through adaptive rewiring:
      progressive adaptation of structure to use, creating short-cuts where network
      diffusion is intensive while annihilating underused connections. With adaptive
      rewiring as the engine of universal small-worldness, overall diffusion rate tunes
      the systems' adaptation, biasing local or global connectivity patterns. Whereas
      the former leads to modularity, the latter provides a preferential attachment
      regime. As the latter sets in, the resulting small-world structures undergo a
      critical shift from modular (decentralised) to centralised ones. At the
      transition point, network structure is hierarchical, balancing modularity and
      centrality - a characteristic feature found in, for instance, the human brain.

PMID- 29030609
TI  - Signatures of positive selection reveal a universal role of chromatin modifiers
      as cancer driver genes.
AB  - Tumors are composed of an evolving population of cells subjected to tissue
      specific selection, which fuels tumor heterogeneity and ultimately complicates
      cancer driver gene identification. Here, we integrate cancer cell fraction,
      population recurrence, and functional impact of somatic mutations as signatures
      of selection into a Bayesian model for driver prediction. We demonstrate that our
      model, cDriver, outperforms competing methods when analyzing solid tumors,
      hematological malignancies, and pan-cancer datasets. Applying cDriver to exome
      sequencing data of 21 cancer types from 6,870 individuals revealed 98 unreported
      tumor type-driver gene connections. These novel connections are highly enriched
      for chromatin-modifying proteins, hinting at a universal role of chromatin
      regulation in cancer etiology. Although infrequently mutated as single genes, we
      show that chromatin modifiers are altered in a large fraction of cancer patients.
      In summary, we demonstrate that integration of evolutionary signatures is key for
      identifying mutational driver genes, thereby facilitating the discovery of novel
      therapeutic targets for cancer treatment.

PMID- 29030610
TI  - Angiotensin-converting enzyme Ance is cooperatively regulated by Mad and Pannier
      in Drosophila imaginal discs.
AB  - Angiotensin-converting enzyme (ACE) is an evolutionarily conserved peptidyl
      dipeptidase. Mammalian ACE converts angiotensin I to the active vasoconstrictor
      angiotensin II, thus playing a critical role for homeostasis of the renin
      angiotensin system. In Drosophila, the ACE homolog Ance is expressed in specific
      regions of developing organs, but its regulatory mechanism has not been
      identified. Here we provide evidence that Ance expression is regulated by a
      combination of Mad and Pannier (Pnr) in imaginal discs. We demonstrate that Ance
      expression in eye and wing discs depends on Dpp signaling. The Mad binding site
      of Ance regulatory region is essential for Ance expression. Ance expression in
      imaginal discs is also regulated by the GATA family transcription factor Pnr. Pnr
      directly regulates Ance expression by binding to a GATA site of Ance enhancer. In
      addition, Pnr and Mad physically and genetically interact. Ance null mutants are
      morphologically normal but show genetic interaction with dpp mutants.
      Furthermore, we show that human SMAD2 and GATA4 physically interact and ACE
      expression in HEK293 cells is regulated by SMAD2 and GATA4. Taken together, this
      study reveals a cooperative mechanism of Ance regulation by Mad and Pnr. Our data
      also suggest a conserved transcriptional regulation of human ACE.

PMID- 29030611
TI  - DNA methylation and transcriptional trajectories during human development and
      reprogramming of isogenic pluripotent stem cells.
AB  - Determining cell identity and maturation status of differentiated pluripotent
      stem cells (PSCs) requires knowledge of the transcriptional and epigenetic
      trajectory of organs during development. Here, we generate a transcriptional and
      DNA methylation atlas covering 21 organs during human fetal development. Analysis
      of multiple isogenic organ sets shows that organ-specific DNA methylation
      patterns are highly dynamic between week 9 (W9) and W22 of gestation. We
      investigate the impact of reprogramming on organ-specific DNA methylation by
      generating human induced pluripotent stem cell (hiPSC) lines from six isogenic
      organs. All isogenic hiPSCs acquire DNA methylation patterns comparable to
      existing hPSCs. However, hiPSCs derived from fetal brain retain brain-specific
      DNA methylation marks that seem sufficient to confer higher propensity to
      differentiate to neural derivatives. This systematic analysis of human fetal
      organs during development and associated isogenic hiPSC lines provides insights
      in the role of DNA methylation in lineage commitment and epigenetic reprogramming
      in humans.While DNA methylation and gene expression data are widely available for
      animal models, comprehensive data from human development is rarer. Here, the
      authors generated transcriptional and DNA methylation data from 21 organs during
      human development and 6 isogenic induced pluripotent stem cell lines.

PMID- 29030612
TI  - Healing of Preterm Ruptured Fetal Membranes.
AB  - Preterm premature rupture of membrane (pPROM) is associated with 30-40% of
      preterm births. Infection is considered a leading cause of pPROM due to increased
      levels of proinflammatory cytokines in amniotic fluid. Only 30%, however, are
      positive for microbial organisms by amniotic fluid culture. Interestingly, in
      some pregnancies complicated by preterm premature rupture of membranes (pPROM),
      membranes heal spontaneously and pregnancy continues until term. Here, we
      investigated mechanisms of amnion healing. Using a preclinical mouse model, we
      found that small ruptures of the fetal membrane closed within 72 h whereas
      healing of large ruptures was only 40%. Small rupture induced transient
      upregulation of cytokines whereas large ruptures elicited sustained upregulation
      of proinflammatory cytokines in the fetal membranes. Fetal macrophages from
      amniotic fluid were recruited to the wounded amnion where macrophage adhesion
      molecules were highly expressed. Recruited macrophages released limited and well
      localized amounts of IL-1beta and TNF which facilitated epithelial-mesenchymal
      transition (EMT) and epithelial cell migration. Arg1 + macrophages dominated
      within 24 h. Migration and healing of the amnion mesenchymal compartment,
      however, remained compromised. These findings provide novel insights regarding
      unique healing mechanisms of amnion.

PMID- 29030613
TI  - Lipopolysaccharide enters the rat brain by a lipoprotein-mediated transport
      mechanism in physiological conditions.
AB  - Physiologically, lipopolysaccharide (LPS) is present in the bloodstream and can
      be bound to several proteins for its transport (i.e.) LPS binding protein (LBP)
      and plasma lipoproteins). LPS receptors CD14 and TLR-4 are constitutively
      expressed in the Central Nervous System (CNS). To our knowledge, LPS infiltration
      in CNS has not been clearly demonstrated. A naturalistic experiment with healthy
      rats was performed to investigate whether LPS is present with its receptors in
      brain. Immunofluorescences showed that lipid A and core LPS were present in
      circumventricular organs, choroid plexus, meningeal cells, astrocytes, tanycytes
      and endothelial cells. Co-localization of LPS regions with CD14/TLR-4 was found.
      The role of lipoprotein receptors (SR-BI, ApoER2 and LDLr) in the brain as
      targets for a LPS transport mechanism by plasma apolipoproteins (i.e. ApoAI) was
      studied. Co-localization of LPS regions with these lipoproteins markers was
      observed. Our results suggest that LPS infiltrates in the brain in physiological
      conditions, possibly, through a lipoprotein transport mechanism, and it is bound
      to its receptors in blood-brain interfaces.

PMID- 29030614
TI  - Retinal Degeneration Protein 3 (RD3) in normal human tissues: Novel insights.
AB  - The 195-amino-acid-long human Retinal Degeneration Protein 3 (RD3) is critical in
      the regulation of guanylate cyclase (GC) signaling and photoreceptor cell
      survival. Recently, we identified significant loss of RD3 in high-risk
      neuroblastoma and the influential role of RD3 in tumor progression. However, the
      functional characterization of RD3 in tumor systems has been hampered by the
      dearth of information on its localization in normal tissue and by the lack of
      antibodies suitable for staining FFPE tissue, primarily due to the
      inaccessibility of the epitopes. In this study, we validated a custom-synthesized
      RD3 antibody and investigated the expression/localization of RD3 in assorted
      human tissues. We observed stratified expression of RD3 in different cell types
      and subcellular location of retina. We demonstrated extensive positive RD3
      immunoreactivity in various normal tissues and particularly strong dot-like
      perinuclear staining in the lining epithelial cells, suggesting that RD3 may play
      an important role in the normal functioning of epithelial cells. RD3 expression
      is limited in the CNS. While neuroblastoma is often RD3-positive, the adrenal
      medulla, where many neuroblastomas originate, is RD3-negative. Meta-analysis of
      RD3 transcriptional expression across normal tissues confirmed tissue-specific
      RD3 mRNA levels. Our results revealed the tissue-specific expression/localization
      profile of RD3 for the first time.

PMID- 29030615
TI  - Electrokinetic Analysis of Energy Harvest from Natural Salt Gradients in
      Nanochannels.
AB  - The Gibbs free energy released during the mixing of river and sea water has been
      illustrated as a promising source of clean and renewable energy. Reverse
      electrodialysis (RED) is one major strategy to gain electrical power from this
      natural salinity, and recently by utilizing nanochannels a novel mode of this
      approach has shown improved power density and energy converting efficiency. In
      this work, we carry out an electrokinetic analysis of the work extracted from RED
      in the nanochannels. First, we outline the exclusion potential effect induced by
      the inhomogeneous distribution of extra-counterions along the channel axis. This
      effect is unique in nanochannel RED and how to optimize it for energy harvesting
      is the central topic of this work. We then discuss two important indexes of
      performance, which are the output power density and the energy converting
      efficiency, and their dependence on the nanochannel parameters such as channel
      material and geometry. In order to yield maximized output electrical power, we
      propose a device design by stepwise usage of the saline bias, and the lengths of
      the nanochannels are optimized to achieve the best trade-off between the input
      thermal power and the energy converting efficiency.

PMID- 29030616
TI  - Maternal consumption of fish oil programs reduced adiposity in broiler chicks.
AB  - Maternal intake of eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid
      (22:6 n-3) has been associated with reduced adiposity in children, suggesting the
      possibility to program adipose development through dietary fatty acids before
      birth. This study determined if enriching the maternal diet in fish oil, the
      primary source of EPA and DHA, affected adipose development in offspring. Broiler
      chickens were used because they are obesity-prone, and because fatty acids
      provided to the embryo can be manipulated through the hen diet. Hens were fed
      diets supplemented (2.8% wt:wt) with corn oil (CO; n-6) or fish oil (FO; n-3) for
      28 d. Chicks from both maternal diet groups were fed the same diet after hatch.
      Maternal FO consumption enriched chick adipose tissue in EPA and DHA and reduced
      adiposity by promoting more, but smaller, adipocytes. This adipocyte profile was
      paralleled by upregulated expression of the adipogenic regulator PPARG and its co
      activator PPARGC1B, and reduced expression of LPL. Proteomics identified 95
      differentially abundant proteins between FO and CO adipose tissue, including
      components of glucose metabolism, lipid droplet trafficking, and cytoskeletal
      organization. These results demonstrate that the maternal dietary fatty acid
      profile programs offspring adipose development.

PMID- 29030617
TI  - Oxygen isotope anomaly in tropospheric CO2 and implications for CO2 residence
      time in the atmosphere and gross primary productivity.
AB  - The abundance variations of near surface atmospheric CO2 isotopologues (primarily
      16O12C16O, 16O13C16O, 17O12C16O, and 18O12C16O) represent an integrated signal
      from anthropogenic/biogeochemical processes, including fossil fuel burning,
      biospheric photosynthesis and respiration, hydrospheric isotope exchange with
      water, and stratospheric photochemistry. Oxygen isotopes, in particular, are
      affected by the carbon and water cycles. Being a useful tracer that directly
      probes governing processes in CO2 biogeochemical cycles, Delta17O (=ln(1 +
      delta17O) - 0.516 * ln(1 + delta18O)) provides an alternative constraint on the
      strengths of the associated cycles involving CO2. Here, we analyze Delta17O data
      from four places (Taipei, Taiwan; South China Sea; La Jolla, United States;
      Jerusalem, Israel) in the northern hemisphere (with a total of 455 measurements)
      and find a rather narrow range (0.326 +/- 0.0050/00). A conservative estimate
      places a lower limit of 345 +/- 70 PgC year-1 on the cycling flux between the
      terrestrial biosphere and atmosphere and infers a residence time of CO2 of 1.9 +/
      0.3 years (upper limit) in the atmosphere. A Monte Carlo simulation that takes
      various plant uptake scenarios into account yields a terrestrial gross primary
      productivity of 120 +/- 30 PgC year-1 and soil invasion of 110 +/- 30 PgC year-1,
      providing a quantitative assessment utilizing the oxygen isotope anomaly for
      quantifying CO2 cycling.

PMID- 29030618
TI  - Experimental demonstration of magnetoplasmon polariton at InSb(InAs)/dielectric
      interface for terahertz sensor application.
AB  - We experimentally demonstrate surface plasmon resonance (SPR) in the terahertz
      range in InSb and InAs. The surface plasmon is excited on the interface between a
      thin polymer film and the semiconductor using a silicon prism in Otto
      configuration. The low effective mass of InSb and InAs permits tuning of the SPR
      by an external magnetic field in the transversal configuration. The data show a
      good agreement with a model. Strong excitation of the surface plasmon is present
      in both materials, with a shifting of resonance position by more than 100 GHz for
      the field of 0.25 T, to both higher and lower energies with opposite orientation
      of the magnetic field. Applicability of the terahertz SPR sensor is discussed,
      along with modeled design for the Kretschmann configuration.

PMID- 29030619
TI  - Unwavering Pathobiology of Volumetric Muscle Loss Injury.
AB  - Volumetric muscle loss (VML) resulting from extremity trauma presents chronic and
      persistent functional deficits which ultimately manifest disability. Acellular
      biological scaffolds, or decellularized extracellular matrices (ECMs), embody an
      ideal treatment platform due to their current clinical use for soft tissue
      repair, off-the-shelf availability, and zero autogenous donor tissue burden. ECMs
      have been reported to promote functional skeletal muscle tissue remodeling in
      small and large animal models of VML injury, and this conclusion was reached in a
      recent clinical trial that enrolled 13 patients. However, numerous other pre
      clinical reports have not observed ECM-mediated skeletal muscle regeneration. The
      current study was designed to reconcile these discrepancies. The capacity of ECMs
      to orchestrate functional muscle tissue remodeling was interrogated in a porcine
      VML injury model using unbiased assessments of muscle tissue regeneration and
      functional recovery. Here, we show that VML injury incites an overwhelming
      inflammatory and fibrotic response that leads to expansive fibrous tissue
      deposition and chronic functional deficits, which ECM repair does not augment.

PMID- 29030620
TI  - Transcriptomic profiles of Clostridium ljungdahlii during lithotrophic growth
      with syngas or H2 and CO2 compared to organotrophic growth with fructose.
AB  - Clostridium ljungdahlii derives energy by lithotrophic and organotrophic
      acetogenesis. C. ljungdahlii was grown organotrophically with fructose and also
      lithotrophically, either with syngas - a gas mixture containing hydrogen (H2),
      carbon dioxide (CO2), and carbon monoxide (CO), or with H2 and CO2. Gene
      expression was compared quantitatively by microarrays using RNA extracted from
      all three conditions. Gene expression with fructose and with H2/CO2 was compared
      by RNA-Seq. Upregulated genes with both syngas and H2/CO2 (compared to fructose)
      point to the urea cycle, uptake and degradation of peptides and amino acids,
      response to sulfur starvation, potentially NADPH-producing pathways involving (S)
      malate and ornithine, quorum sensing, sporulation, and cell wall remodeling,
      suggesting a global and multicellular response to lithotrophic conditions. With
      syngas, the upregulated (R)-lactate dehydrogenase gene represents a route of
      electron transfer from ferredoxin to NAD. With H2/CO2, flavodoxin and histidine
      biosynthesis genes were upregulated. Downregulated genes corresponded to an
      intracytoplasmic microcompartment for disposal of methylglyoxal, a toxic
      byproduct of glycolysis, as 1-propanol. Several cytoplasmic and membrane
      associated redox-active protein genes were differentially regulated. The
      transcriptomic profiles of C. ljungdahlii in lithotrophic and organotrophic
      growth modes indicate large-scale physiological and metabolic differences,
      observations that may guide biofuel and commodity chemical production with this
      species.

PMID- 29030621
TI  - Flow cytometry as a rapid analytical tool to determine physiological responses to
      changing O2 and iron concentration by Magnetospirillum gryphiswaldense strain MSR
      1.
AB  - Magnetotactic bacteria (MTB) are a diverse group of bacteria that synthesise
      magnetosomes, magnetic membrane-bound nanoparticles that have a variety of
      diagnostic, clinical and biotechnological applications. We present the
      development of rapid methods using flow cytometry to characterize several aspects
      of the physiology of the commonly-used MTB Magnetospirillum gryphiswaldense MSR
      1. Flow cytometry is an optical technique that rapidly measures characteristics
      of individual bacteria within a culture, thereby allowing determination of
      population heterogeneity and also permitting direct analysis of bacteria. Scatter
      measurements were used to measure and compare bacterial size, shape and
      morphology. Membrane permeability and polarization were measured using the dyes
      propidium iodide and bis-(1,3-dibutylbarbituric acid) trimethine oxonol to
      determine the viability and 'health' of bacteria. Dyes were also used to
      determine changes in concentration of intracellular free iron and
      polyhydroxylakanoate (PHA), a bacterial energy storage polymer. These tools were
      then used to characterize the responses of MTB to different O2 concentrations and
      iron-sufficient or iron-limited growth. Rapid analysis of MTB physiology will
      allow development of bioprocesses for the production of magnetosomes, and will
      increase understanding of this fascinating and useful group of bacteria.

PMID- 29030622
TI  - Sandwich-structured C/C-SiC composites fabricated by electromagnetic-coupling
      chemical vapor infiltration.
AB  - Carbon fiber (CF) reinforced carbon-silicon carbide (C/C-SiC) composites are one
      of the most promising lightweight materials for re-entry thermal protection,
      rocket nozzles and brake discs applications. In this paper, a novel sandwich
      structured C/C-SiC composite, containing two exterior C/SiC layers, two gradient
      C/C-SiC layers and a C/C core, has been designed and fabricated by two-step
      electromagnetic-coupling chemical vapor infiltration (E-CVI) for a 20-hour
      deposition time. The cross-section morphologies, interface microstructures and
      SiC-matrix growth characteristics and compositions of the composites were
      characterized by scanning electron microscopy (SEM), transmission electron
      microscopy (TEM) and X-ray diffraction (XRD), respectively. Microstructure
      characterization indicates that the SiC growth includes an initial amorphous SiC
      zone, a gradual crystallization of SiC and grow-up of nano-crystal, and a
      columnar grain region. The sandwich structure, rapid deposition rate and growth
      characteristics are attributed to the formation of thermal gradient and the
      establishment of electromagnetic field in the E-CVI process. The composite
      possesses low density of 1.84 g/cm3, high flexural strength of 325 MPa, and low
      linear ablation rate of 0.38 MUm/s under exposure to 5-cycle oxyacetylene flame
      for 1000 s at ~1700  degrees C.

PMID- 29030623
TI  - Monitoring cerebral hemodynamic change during transcranial ultrasound stimulation
      using optical intrinsic signal imaging.
AB  - Transcranial ultrasound stimulation (tUS) is a promising non-invasive approach to
      modulate brain circuits. The application is gaining popularity, however the full
      effect of ultrasound stimulation is still unclear and further investigation is
      needed. This study aims to apply optical intrinsic signal imaging (OISI) for the
      first time, to simultaneously monitor the wide-field cerebral hemodynamic change
      during tUS on awake animal with high spatial and temporal resolution. Three
      stimulation paradigms were delivered using a single-element focused transducer
      operating at 425 kHz in pulsed mode having the same intensity (ISPPA = 1.84
      W/cm2, ISPTA = 129 mW/cm2) but varying pulse repetition frequencies (PRF). The
      results indicate a concurrent hemodynamic change occurring with all actual tUS
      but not under a sham stimulation. The stimulation initiated the increase of
      oxygenated hemoglobin (HbO) and decrease of deoxygenated hemoglobin (RHb). A
      statistically significant difference (p < 0.05) was found in the amplitude change
      of hemodynamics evoked by varying PRF. Moreover, the acoustic stimulation was
      able to trigger a global as well as local cerebral hemodynamic alteration in the
      mouse cortex. Thus, the implementation of OISI offers the possibility of directly
      investigating brain response in an awake animal during tUS through cerebral
      hemodynamic change.

PMID- 29030624
TI  - Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms.
AB  - Psilocybin with psychological support is showing promise as a treatment model in
      psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral
      blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional
      connectivity (RSFC) were measured with functional magnetic resonance imaging
      (fMRI) before and after treatment with psilocybin (serotonin agonist) for
      treatment-resistant depression (TRD). Quality pre and post treatment fMRI data
      were collected from 16 of 19 patients. Decreased depressive symptoms were
      observed in all 19 patients at 1-week post-treatment and 47% met criteria for
      response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in
      CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF
      correlated with reduced depressive symptoms. Focusing on a priori selected
      circuitry for RSFC analyses, increased RSFC was observed within the default-mode
      network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral
      inferior lateral parietal cortex RSFC was predictive of treatment response at 5
      weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill
      an important knowledge gap regarding the post-treatment brain effects of
      psilocybin, and are the first in depressed patients. The post-treatment brain
      changes are different to previously observed acute effects of psilocybin and
      other 'psychedelics' yet were related to clinical outcomes. A 'reset' therapeutic
      mechanism is proposed.

PMID- 29030625
TI  - Pharmacological HIF-inhibition attenuates postoperative adhesion formation.
AB  - Peritoneal adhesions represent a common complication of abdominal surgery, and
      tissue hypoxia is a main determinant in adhesion formation. Reliable therapeutic
      options to reduce peritoneal adhesions are scarce. We investigated whether the
      formation of postsurgical adhesions can be affected by pharmacological
      interference with hypoxia-inducible factors (HIFs). Mice were treated with a
      small molecule HIF-inhibitor, YC-1 (3-[5'-Hydroxymethyl-2'-furyl]-1-benzyl
      indazole), or vehicle three days before and seven days after induction of
      peritoneal adhesions or, alternatively, once during induction of peritoneal
      adhesions. Pretreatment or single intraperitoneal lavage with YC-1 significantly
      reduced postoperative adhesion formation without prompting systemic adverse
      effects. Expression analyses of cytokines in peritoneal tissue and fluid and in
      vitro assays applying macrophages and peritoneal fibroblasts indicated that this
      effect was cooperatively mediated by various putatively HIF-1alpha-dependent
      mechanisms, comprising attenuated pro-inflammatory activation of macrophages,
      impaired recruitment and activation of peritoneal fibroblasts, mitigated
      epithelial-mesenchymal-transition (EMT), as well as enhanced fibrinolysis and
      impaired angiogenesis. Thus, this study identifies prevention of postsurgical
      peritoneal adhesions as a novel and promising field for the application of HIF
      inhibitors in clinical practice.

PMID- 29030626
TI  - Pectin methylesterases contribute the pathogenic differences between races 1 and
      4 of Fusarium oxysporum f. sp. cubense.
AB  - Plant cell walls, which are mainly composed of pectin, play important roles in
      plant defence responses to pathogens. Pectin is synthesised in a highly
      esterified form and then de-esterified by pectin methylesterases (PMEs). Because
      of this, PMEs are directly involved in plant defence. However, the molecular
      mechanisms of their interactions with pectins remain unclear. In this study, we
      compared the expression level and enzyme activities of PMEs in a banana Cavendish
      cultivar (Musa AAA 'Brazilian') inoculated with Fusarium oxysporum f. sp. cubense
      pathogenic races 1 (Foc1) and 4 (Foc4). We further examined the spatial
      distribution of PMEs and five individual homogalacturonans (HGs) with different
      degree of pectin methylesterification (DM). Results suggested that the banana
      roots infected with Foc1 showed lower PME activity than those infected with Foc4,
      which was consisted with observed higher level of pectin DM. The level of HGs
      crosslinked with Ca2+ was significantly higher in roots infected with Foc1
      compared with those infected with Foc4. Therefore, banana exhibited significantly
      different responses to Foc1 and Foc4 infection, and these results suggest
      differences in PME activities, DM of pectin and Ca2+-bridged HG production. These
      differences could have resulted in observed differences in virulence between Foc1
      and Foc4.

PMID- 29030627
TI  - Different levels of glyphosate-resistant Lolium rigidum L. among major crops in
      southern Spain and France.
AB  - Herbicides are the most effective tools for controlling almost 99% of weeds.
      However, herbicide resistance is a primary concern in modern agriculture. The
      characterization in new areas and elucidation of the mechanisms of resistance are
      of vital importance in maintaining the sustainability of herbicides, including
      glyphosate. Nine populations of Lolium rigidum, showing different response
      patterns, were characterized as being glyphosate resistant (GR). The wide range
      of values in fresh weight reduction, survival, shikimic acid and EPSPS enzyme
      activity indicates a different or a combination resistance mechanism. The Line-3
      population resulted in minimum reduction of fresh weight and survival values with
      respect to the glyphosate-susceptible (GS) population, showing 16.05- and 17.90
      fold higher values, respectively. There were significant differences in the 14C
      glyphosate translocation between GR and GS populations. Moreover, there were
      differences among the nine GR populations, but they exhibited a reduction in the
      remaining glyphosate translocation in the treated leaf. The EPSPS gene sequence
      revealed a Pro-106-Ser substitution in four populations, which could be
      characterized as being GR with non-target-site and target-site resistance
      mechanisms. This complexity of several resistance mechanisms makes it necessary
      to develop long-term integrated weed management strategies to limit further
      resistance dispersal.

PMID- 29030628
TI  - Synthetic/ECM-inspired hybrid platform for hollow microcarriers with ROS
      triggered nanoporation hallmarks.
AB  - Reactive oxygen species (ROS) are key pathological signals expressed in
      inflammatory diseases such as cancer, ischemic conditions and atherosclerosis. An
      ideal drug delivery system should not only be responsive to these signals but
      also should not elicit an unfavourable host response. This study presents an
      innovative platform for drug delivery where a natural/synthetic composite system
      composed of collagen type I and a synthesized polythioether, ensures a dual
      stimuli-responsive behaviour. Collagen type I is an extracellular matrix
      constituent protein, responsive to matrix metalloproteinases (MMP) cleavage per
      se. Polythioethers are stable synthetic polymers characterized by the presence of
      sulphur, which undergoes a ROS-responsive swelling switch. A polythioether was
      synthesised, functionalized and tested for cytotoxicity. Optimal conditions to
      fabricate a composite natural/synthetic hollow sphere construct were optimised by
      a template-based method. Collagen-polythioether hollow spheres were fabricated,
      revealing uniform size and ROS-triggered nanoporation features. Cellular
      metabolic activity of H9C2 cardiomyoblasts remained unaffected upon exposure to
      the spheres. Our natural/synthetic hollow microspheres exhibit the potential for
      use as a pathological stimuli-responsive reservoir system for applications in
      inflammatory diseases.

PMID- 29030629
TI  - Decadal Western Pacific Warm Pool Variability: A Centroid and Heat Content Study.
AB  - We examine several characteristics of the Western Pacific Warm Pool (WP) in the
      past thirty years of mixed interannual variability and climate change. Our study
      presents the three-dimensional WP centroid (WPC) movement, WP heat content
      anomaly (HC) and WP volume (WPV) on interannual to decadal time scales. We show
      the statistically significant correlation between each parameter's interannual
      anomaly and the NINO 3, NINO 3.4, NINO 4, SOI, and PDO indices. The longitudinal
      component of the WPC is most strongly correlated with NINO 4 (R = 0.78). The
      depth component of the WPC has the highest correlation (R = -0.6) with NINO3.4.
      The WPV and NINO4 have an R-Value of -0.65. HC has the highest correlation with
      NINO3.4 (R = -0.52). During the study period of 1982-2014, the non-linear trends,
      derived from ensemble empirical mode decomposition (EEMD), show that the WPV, WP
      depth and HC have all increased. The WPV has increased by 14% since 1982 and the
      HC has increased from -1 * 108 J/m2 in 1993 to 10 * 108 J/m2 in 2014. While the
      largest variances in the latitudinal and longitudinal WPC locations are
      associated with annual and seasonal timescales, the largest variances in the WPV
      and HC are due to the multi-decadal non-linear trend.

PMID- 29030630
TI  - Ecosystem carbon storage in forest fragments of differing patch size.
AB  - Forest fragmentation threatens the ecosystem carbon (C) storage. The distribution
      patterns of ecosystem C density are poorly documented for fragmented forests of
      differing patch size. The objectives of this study were to examine C density in
      these forest ecosystems and the influence of edge effects on C density.
      Allometric equations were used to quantify aboveground biomass. Carbon density
      was estimated by analyzing the C concentration of each component. We found that
      ecosystem carbon density ranged from 173.9 Mg ha-1 in the small sized forest
      fragments, to 341.1 Mg ha-1 in the contiguous evergreen sub-tropical forest.
      Trees (46.5%) and mineral soil (50.2%) were the two largest contributors to the
      total ecosystem C pool in all fragments. Both C and nitrogen (N) in soil and fine
      roots were highly heterogeneous among the different fragment sizes and soil
      depths. We concluded that ecosystem C density of forest fragments were
      significantly influenced by patch size and edge effects. The fragmented forests
      in southern China play an important role in the C budget, and need urgent
      conservation. These results are likely to be further integrated into forest
      management plans and generalized into other contexts, to evaluate C stocks at the
      landscape scale.

PMID- 29030631
TI  - Viscosity is an important factor of resistance to alcohol-based disinfectants by
      pathogens present in mucus.
AB  - Alcohol-based disinfectants play an important role in the prevention of
      healthcare-acquired infection (HAI). We investigated whether pathogens present in
      mucus acquire resistance to alcohol-based disinfectants, and elucidated the
      underlying mechanism. Both the resistance of influenza A virus and Escherichia
      coli to alcohol-based disinfectants or ultraviolet irradiation and the diffusion
      rate of ethanol were determined in artificial mucus or sputum samples obtained
      from 27 individuals with acute upper respiratory infection. Pathogens in mucus
      (artificial mucus or sputum samples) were not completely inactivated by alcohol
      based disinfectants (survival rate >10%), suggesting that the alcohol-based
      disinfectants were ineffective. Pathogen survival and mucus viscosity were
      strongly correlated (correlation coefficient >0.7, P < 0.001). Additionally, the
      ethanol diffusion rate decreased with increasing mucus viscosity, which
      contributed to ethanol resistance. Pronase treatment of sputum samples
      significantly decreased sputum viscosity and increased the disinfectant effect (P
      < 0.001 for all). In contrast, complete inactivation was achieved by ultraviolet
      irradiation independently of mucus viscosity. Thus, mucus viscosity contributes
      to resistance of pathogens to alcohol-based disinfectants by decreasing the
      alcohol diffusion rate. These findings can provide a basis for developing new
      strategies, including improved disinfectants, for overcoming HAI.

PMID- 29030633
TI  - The best platinum regimens for chemo-naive incurable non-small cell lung cancer:
      network meta-analysis.
AB  - Platinum regimens still play a key role in chemotherapy for incurable non-small
      cell lung cancer (NSCLC). Although guidelines list many platina regimens, the
      best regimens have not yet clarified. Electronic searches were carried out during
      November 26th-28th, 2016. We included individually randomized trials comparing
      two or more platinum regimes for incurable chemo-naive NSCLC published in English
      full papers. The platinum doublets should be either Cisplatin (CDDP), Carboplatin
      (CBDCA), or Nedaplatin (CDGP) plus one of the third-generation agents. The
      platinum triplet should be the doublet plus bevacizumab (BEV). The data were
      independently extracted and cross-checked by two investigators. We did not
      observed heterogeneity (whole network level Q = 28.9, df = 34, P = 0.717) among
      59 pairwise comparisons from 45 studies with 16141 cases for the primary outcome,
      hazard ratio for overall survival (HRos). Using CBDCA + Paclitaxel (PTX) + BEV as
      a common comparator, CDGP + Docetaxel (DTX) (HRos = 0.98, 95%CI: 0.75-1.29, P =
      0.884), CDDP + Tegafur gimeracil oteracil (S1) (HRos = 1.23, 95%CI: 0.96-1.57, P
      = 0.099), CBDCA + S1 (HRos = 1.23, 95%CI: 0.99-1.53, P = 0.062), and CDGP +
      Gemcitabine (GEM) (HRos = 1.24, 95%CI: 0.71-2.17, P = 0.45) did not have
      significantly poorer HRos. We suggest that these regimens as acceptable first
      choice regimens.

PMID- 29030632
TI  - Long-lasting antiviral innate immune priming in the Lophotrochozoan Pacific
      oyster, Crassostrea gigas.
AB  - In the last decade, a paradigm shift has emerged in comparative immunology.
      Invertebrates can no longer be considered to be devoid of specific recognition
      and immune memory. However, we still lack a comprehensive view of these phenomena
      and their molecular mechanisms across phyla, especially in terms of duration,
      specificity, and efficiency in a natural context. In this study, we focused on a
      Lophotrochozoan/virus interaction, as antiviral priming is mostly overlooked in
      molluscs. Juvenile Crassostrea gigas oysters experience reoccurring mass
      mortalities events from Ostreid herpes virus 1 with no existing therapeutic
      treatment. Our results showed that various nucleic acid injections can prime
      oysters to trigger an antiviral state ultimately protecting them against a
      subsequent viral infection. Focusing on poly(I:C) as elicitor, we evidenced that
      it protected from an environmental infection, by mitigating viral replication.
      That protection seemed to induce a specific antiviral response as poly(I:C) fails
      to protect against a pathogenic bacteria. Finally, we showed that this phenomenon
      was long-lasting, persisting for at least 5 months thus suggesting for the first
      time the existence of innate immune memory in this invertebrate species. This
      study strengthens the emerging hypotheses about the broad conservation of innate
      immune priming and memory mechanisms in Lophotrochozoans.

PMID- 29030634
TI  - X-ray spectroscopic study of amorphous and polycrystalline PbO films, alpha-PbO,
      and beta-PbO for direct conversion imaging.
AB  - We investigated the electronic structure of Lead Oxide (PbO) - one of the most
      promising photoconductor materials for direct conversion x-ray imaging detectors,
      using soft x-ray emission and absorption spectroscopy. Two structural
      configurations of thin PbO layers, namely the polycrystalline and the amorphous
      phase, were studied, and compared to the properties of powdered alpha-PbO and
      beta-PbO samples. In addition, we performed calculations within the framework of
      density functional theory and found an excellent agreement between the calculated
      and the measured absorption and emission spectra, which indicates high accuracy
      of our structural models. Our work provides strong evidence that the electronic
      structure of PbO layers, specifically the width of the band gap and the presence
      of additional interband and intraband states in both conduction and valence band,
      depend on the deposition conditions. We tested several model structures using DFT
      simulations to understand what the origin of these states is. The presence of O
      vacancies is the most plausible explanation for these additional electronic
      states. Several other plausible models were ruled out including interstitial O,
      dislocated O and the presence of significant lattice stress in PbO.

PMID- 29030635
TI  - Entanglement of photons in their dual wave-particle nature.
AB  - Wave-particle duality is the most fundamental description of the nature of a
      quantum object, which behaves like a classical particle or wave depending on the
      measurement apparatus. On the other hand, entanglement represents nonclassical
      correlations of composite quantum systems, being also a key resource in quantum
      information. Despite the very recent observations of wave-particle superposition
      and entanglement, whether these two fundamental traits of quantum mechanics can
      emerge simultaneously remains an open issue. Here we introduce and experimentally
      realize a scheme that deterministically generates entanglement between the wave
      and particle states of two photons. The elementary tool allowing this achievement
      is a scalable single-photon setup which can be in principle extended to generate
      multiphoton wave-particle entanglement. Our study reveals that photons can be
      entangled in their dual wave-particle behavior and opens the way to potential
      applications in quantum information protocols exploiting the wave-particle
      degrees of freedom to encode qubits.Here the authors experimentally realize a
      scheme that deterministically generates entanglement between the wave and
      particle states of two photons using a scalable all-optical scheme. They achieve
      this result by first showing generation of controllable single-photon wave
      particle superposition states.

PMID- 29030636
TI  - Cancer-associated fibroblasts induce metalloprotease-independent cancer cell
      invasion of the basement membrane.
AB  - At the stage of carcinoma in situ, the basement membrane (BM) segregates tumor
      cells from the stroma. This barrier must be breached to allow dissemination of
      the tumor cells to adjacent tissues. Cancer cells can perforate the BM using
      proteolysis; however, whether stromal cells play a role in this process remains
      unknown. Here we show that an abundant stromal cell population, cancer-associated
      fibroblasts (CAFs), promote cancer cell invasion through the BM. CAFs facilitate
      the breaching of the BM in a matrix metalloproteinase-independent manner.
      Instead, CAFs pull, stretch, and soften the BM leading to the formation of gaps
      through which cancer cells can migrate. By exerting contractile forces, CAFs
      alter the organization and the physical properties of the BM, making it
      permissive for cancer cell invasion. Blocking the ability of stromal cells to
      exert mechanical forces on the BM could therefore represent a new therapeutic
      strategy against aggressive tumors.Stromal cells play various roles in tumor
      establishment and metastasis. Here the authors, using an ex-vivo model, show that
      cancer-associated fibroblasts facilitate colon cancer cells invasion in a matrix
      metalloproteinase-independent manner, likely by pulling and stretching the
      basement membrane to form gaps.

PMID- 29030637
TI  - Molecular Mechanisms of the Binding and Specificity of Streptococcus Pneumoniae
      Sortase C Enzymes for Pilin Subunits.
AB  - Pili are elongated structures that protrude from bacteria and increase their
      virulence. The Streptococcus pnuenomae pilus island 1 pili are composed of three
      subunits, RrgA, RrgB, and RrgC, and are assembled by three class C sortase C
      (SrtC) enzymes: SrtC-1, SrtC-2, and SrtC-3. Pilin subunits are recognized by SrtC
      proteins through a pentapeptide sorting signal, and while previous studies have
      sought to characterize the selectivities of SrtC isoforms for these subunits, the
      molecular mechanisms underlying these interactions remain unclear. Here, we
      report a series of molecular dynamics simulations of each SrtC enzyme with the
      sorting signals of RrgA, RrgB, and RrgC to determine the structural and
      thermodynamic basis of pilin recognition. Results show that, in accordance with
      previous studies, both SrtC-1 and SrtC-3 are selective for RrgB, while SrtC-2 is
      selective for RrgA. This specificity is tuned by the sorting signal binding
      conformation in which the first two residue sidechains complement hydrophobic
      residues around the active site, while the third residue projects away from the
      catalytic triad and makes specific interactions based on its charge and reach.
      Together, these results provided atomic-scale descriptions of the SrtC substrate
      selectivity mechanisms and extend the emerging model of pilin construction in S.
      pnuenomae.

PMID- 29030638
TI  - UHPLC-MS/MS determination of varietal thiol precursors in Sauvignon Blanc grapes.
AB  - Varietal thiol precursors in grapes are subject to metabolic changes during post
      harvest treatments. Metabolic activity should therefore be limited after sampling
      to understand their biosynthesis in the berry and genetic regulation. In this
      study, berries were frozen in liquid nitrogen immediately after harvesting,
      transported in dry ice, stored briefly at -80  degrees C, cryo-milled and
      extracted without being thawed in cold methanol in a ratio of 1:4 (w/v). A UHPLC
      MS/MS method for quantitative determination of the thiol precursors 3-S
      glutathionylhexan-1-ol (G3MH), 3-S-cysteinylhexan-1-ol (Cys3MH), 4-S-glutathionyl
      4-methylpentan-2-one (G4MMP) and 4-S-cysteinyl-4-methylpentan-2-one (Cys4MMP),
      glutathione, oxidized glutathione and L-methionine in grapes was developed.
      Reference material was provided through synthesis of precursors and their
      deuterium labelled analogues. The average thiol precursor content in grapes in
      2013-15 was in the range 8-16 MUg kg-1 for G3MH, 1-6 MUg kg-1 for Cys3MH, 1-4 MUg
      kg-1 for Cys4MMP and 0.3 MUg kg-1 for G4MMP. In 2013 and 2014, the highest
      precursor content in mature Sauvignon Blanc grapes from vineyards located in
      Italy regarded G3MH, followed by Cys3MH, Cys4MMP and G4MMP. In 2015, G3MH was
      again the most abundant precursor, but followed by Cys4MMP, Cys3MH and G4MMP.

PMID- 29030639
TI  - Androgen receptor increases hematogenous metastasis yet decreases lymphatic
      metastasis of renal cell carcinoma.
AB  - Clear cell renal cell carcinoma (ccRCC) is a gender-biased tumor. Here we report
      that there is also a gender difference between pulmonary metastasis and lymph
      node metastasis showing that the androgen receptor (AR)-positive ccRCC may prefer
      to metastasize to lung rather than to lymph nodes. A higher AR expression
      increases ccRCC hematogenous metastasis yet decreases ccRCC lymphatic metastases.
      Mechanism dissection indicates that AR enhances miR-185-5p expression via binding
      to the androgen response elements located on the promoter of miR-185-5p, which
      suppresses VEGF-C expression via binding to its 3' UTR. In contrast, AR-enhanced
      miR-185-5p also promotes HIF2alpha/VEGF-A expression via binding to the promoter
      region of HIF2alpha. Together, these results provide a unique mechanism by which
      AR can either increase or decrease ccRCC metastasis at different sites and may
      help us to develop combined therapies using anti-AR and anti-VEGF-C compounds to
      better suppress ccRCC progression.The incidence of renal cell carcinoma is higher
      in males than in females due to the different androgen receptor signaling but the
      molecular mechanisms behind this gender bias are unclear. Here the authors show
      how androgen receptor expression influences the metastatic route through the
      regulation of miR-185 and VEGF isoforms.

PMID- 29030640
TI  - Insights into grapevine defense response against drought as revealed by
      biochemical, physiological and RNA-Seq analysis.
AB  - Grapevine is an important and extensively grown fruit crop, which is severely
      hampered by drought worldwide. So, comprehending the impact of drought on
      grapevine genetic resources is necessary. In the present study, RNA-sequencing
      was executed using cDNA libraries constructed from both drought-stress and
      control plants. Results generated 12,451 differentially expressed genes (DEGs),
      out of which 8,021 genes were up-regulated, and 4,430 were down-regulated.
      Further physiological and biochemical investigations were also performed to
      validate the biological processes associated with the development of grapevine in
      response to drought stress. Results also revealed that decline in the rate of
      stomatal conductance, in turn, decrease the photosynthetic activity and CO2
      assimilation in the grapevine leaves. Reactive oxygen species, including stress
      enzymes and their related proteins, and secondary metabolites were also activated
      in the present study. Likewise, various hormones also induced in response to
      drought stress. Overall, the present study concludes that these DEGs play both
      positive and negative roles in drought tolerance by regulating various biological
      pathways of grapevine. Nevertheless, our findings have provided valuable gene
      information for future studies of abiotic stress in grapevine and various other
      fruit crops.

PMID- 29030641
TI  - Lubricin binds cartilage proteins, cartilage oligomeric matrix protein,
      fibronectin and collagen II at the cartilage surface.
AB  - Lubricin, a heavily O-glycosylated protein, is essential for boundary lubrication
      of articular cartilage. Strong surface adherence of lubricin is required given
      the extreme force it must withstand. Disulfide bound complexes of lubricin and
      cartilage oligomeric matrix protein (COMP) have recently been identified in
      arthritic synovial fluid suggesting they may be lost from the cartilage surface
      in osteoarthritis and inflammatory arthritis. This investigation was undertaken
      to localise COMP-lubricin complexes within cartilage and investigate if other
      cartilage proteins are involved in anchoring lubricin to the joint.
      Immunohistochemical analysis of human cartilage biopsies showed lubricin and COMP
      co-localise to the cartilage surface. COMP knockout mice, however, presented with
      a lubricin layer on the articular cartilage leading to the further investigation
      of additional lubricin binding mechanisms. Proximity ligation assays (PLA) on
      human cartilage biopsies was used to localise additional lubricin binding
      partners and demonstrated that lubricin bound COMP, but also fibronectin and
      collagen II on the cartilage surface. Fibronectin and collagen II binding to
      lubricin was confirmed and characterised by solid phase binding assays with
      recombinant lubricin fragments. Overall, COMP, fibronectin and collagen II bind
      lubricin, exposed on the articular cartilage surface suggesting they may be
      involved in maintaining essential boundary lubrication.

PMID- 29030642
TI  - Saline is as effective as nitrogen scavengers for treatment of hyperammonemia.
AB  - Urea cycle enzyme deficiency (UCED) patients with hyperammonemia are treated with
      sodium benzoate (SB) and sodium phenylacetate (SPA) to induce alternative
      pathways of nitrogen excretion. The suggested guidelines supporting their use in
      the management of hyperammonemia are primarily based on non-analytic studies such
      as case reports and case series. Canine congenital portosystemic shunting (CPSS)
      is a naturally occurring model for hyperammonemia. Here, we performed cross-over,
      randomized, placebo-controlled studies in healthy dogs to assess safety and
      pharmacokinetics of SB and SPA (phase I). As follow-up safety and efficacy of SB
      was evaluated in CPSS-dogs with hyperammonemia (phase II). Pharmacokinetics of SB
      and SPA were comparable to those reported in humans. Treatment with SB and SPA
      was safe and both nitrogen scavengers were converted into their respective
      metabolites hippuric acid and phenylacetylglutamine or phenylacetylglycine, with
      a preference for phenylacetylglycine. In CPSS-dogs, treatment with SB resulted in
      the same effect on plasma ammonia as the control treatment (i.e. saline infusion)
      suggesting that the decrease is a result of volume expansion and/or forced
      diuresis rather than increased production of nitrogenous waste. Consequentially,
      treatment of hyperammonemia justifies additional/placebo-controlled trials in
      human medicine.

PMID- 29030643
TI  - Three-Dimensional Myoarchitecture of the Lower Esophageal Sphincter and
      Esophageal Hiatus Using Optical Sectioning Microscopy.
AB  - Studies to date have failed to reveal the anatomical counterpart of the lower
      esophageal sphincter (LES). We assessed the LES and esophageal hiatus morphology
      using a block containing the human LES and crural diaphragm, serially sectioned
      at 50 MUm intervals and imaged at 8.2 MUm/pixel resolution. A 3D reconstruction
      of the tissue block was reconstructed in which each of the 652 cross sectional
      images were also segmented to identify the boundaries of longitudinal (LM) and
      circular muscle (CM) layers. The CM fascicles on the ventral surface of LES are
      arranged in a helical/spiral fashion. On the other hand, the CM fascicles from
      the two sides cross midline on dorsal surface and continue as sling/oblique
      muscle on the stomach. Some of the LM fascicles of the esophagus leave the
      esophagus to enter into the crural diaphragm and the remainder terminate into the
      sling fibers of the stomach. The muscle fascicles of the right crus of diaphragm
      which form the esophageal hiatus are arranged like a "noose" around the
      esophagus. We propose that circumferential squeeze of the LES and crural
      diaphragm is generated by a unique myo-architectural design, each of which forms
      a "noose" around the esophagus.

PMID- 29030644
TI  - How to prevent the detrimental effects of two months of bed-rest on muscle, bone
      and cardiovascular system: an RCT.
AB  - Physical inactivity leads to a deconditioning of the skeletal, neuromuscular and
      cardiovascular system. It can lead to impaired quality of life, loss of autonomy,
      falls and fractures. Regular exercise would be a logical remedy, but the
      generally recommended high-volume endurance and strength training programs
      require a lot of time and equipment. In this randomized controlled study with 23
      healthy participants, we established that a short, intensive jump training
      program can prevent the large musculoskeletal and cardiovascular deconditioning
      effects caused by two months of physical inactivity during bed rest, particularly
      the loss of bone mineral mass and density, lean muscle mass, maximal leg strength
      and peak oxygen uptake. The jump training group showed no significant changes
      with respect to these indicators of musculoskeletal and cardiovascular health
      after 60 days of bed rest, whereas the control group exhibited substantial
      losses: up to -2.6% in tibial bone mineral content and density, -5% in leg lean
      mass, -40% in maximal knee extension torque and -29% in peak oxygen uptake.
      Consequently, we recommend jump training as a very time-efficient and effective
      type of exercise for astronauts on long-term space missions, the elderly and
      sedentary populations in general.

PMID- 29030645
TI  - No, we are not-we keep forgetting the right ventricle.

PMID- 29030646
TI  - [Systemic treatment of vitiligo : Balance and current developments].
AB  - Systemic drug treatment of vitiligo is currently limited to predominantly
      adjuvant measures for increasing the effectiveness of UV light therapy. We here
      present new approaches for the systemic treatment of vitiligo currently under
      clinical investigation. These include the alpha-MSH-analogue afamelatonide and
      oral immunosuppressants such as the Janus kinase (JAK) inhibitors which target
      interferon-alpha-dependent autotoxic inflammatory reactions. In 2015 the first
      publications on the successful systemic use of Janus kinase (JAK) inhibitors in
      vitiligo appeared. The effectiveness was experimentally supported by animal
      models of vitiligo and by the characterization of new biomarkers in the serum of
      vitiligo patients. This may significantly expand the range of treatment options
      for vitiligo. Topical antiinflammatory and UV therapies are still the main
      components of vitiligo treatment, often in combination. The main outcome
      parameters include the extent and duration of repigmentation, cessation of
      spreading, avoidance of side effects and improvement in the quality of life of
      patients.

PMID- 29030647
TI  - The diagnostic reliability of the quantitative pivot-shift evaluation using an
      electromagnetic measurement system for anterior cruciate ligament deficiency was
      superior to those of the accelerometer and iPad image analysis.
AB  - PURPOSE: Several non-invasive devices have been developed to obtain quantitative
      assessment of the pivot-shift test in clinical setting using similar but diverse
      measurement parameters. However, the clinical usability of those measurements has
      yet to be closely investigated and compared. The purpose of this study was to
      compare the diagnostic accuracy of three non-invasive measurement devices for the
      pivot-shift test. METHODS: Thirty patients with unilateral anterior cruciate
      ligament (ACL) injury were enrolled. The pivot-shift test was performed under
      general anaesthesia. Three devices, an accelerometer system (KiRA), an image
      analysis iPad application (iPad), and electromagnetic measurement system (EMS),
      were used simultaneously to provide two parameters, namely tibial acceleration
      monitored using KiRA and EMS, and tibial translation recorded using iPad and EMS.
      Side-to-side differences in each parameter and correlation between the
      measurements were tested, and a receiver-operating characteristic (ROC) curve
      analysis was conducted to compare their measurement accuracy. RESULTS:
      Significant side-to-side differences were successfully detected using any of the
      measurements (all p < 0.01). KiRA demonstrated moderate correlation with the EMS
      for tibial acceleration (r = 0.54; p < 0.01), while poor correlation was observed
      between iPad and the EMS for the translation (r = 0.28; p < 0.01). The ROC curve
      analysis demonstrated better accuracy for the detection of ACL insufficiency in
      the EMS than KiRA and iPad for tibial acceleration and translation, respectively.
      CONCLUSIONS: Although all three measurements were similarly capable of detecting
      ACL deficiency, the EMS has the advantage of comprehensive evaluation of the
      pivot-shift test by evaluating both tibial acceleration and translation with
      higher accuracy than those of KiRA and iPad. It could be suggested that any of
      those measurement tools might improve the clinical diagnosis of ACL
      insufficiency. LEVEL OF EVIDENCE: Diagnostic study of consecutive patients with a
      universally applied gold standard, Level Ib.

PMID- 29030648
TI  - [Interprofessional symptom management at the end of life].
AB  - At the end of life patients often show distressful symptoms which significantly
      reduce their quality of life. The goal of all healthcare professionals should be
      to recognize the beginning of this end of life period in order to provide good
      symptom management. For this purpose, existing symptoms have to be recorded,
      suitable therapeutic goals have to be defined for the current situation and
      potential therapeutic strategies have to be individually formulated. Besides the
      identification of underlying causes with the possibility of causal treatment, a
      symptom-based therapy is often necessary. Therapeutic approaches of different
      professions should be equally considered and should additionally be used for the
      benefit of the patient.

PMID- 29030649
TI  - The floating bowel sign.

PMID- 29030650
TI  - ThPP1 gene, encodes an inorganic pyrophosphatase in Thellungiella halophila,
      enhanced the tolerance of the transgenic rice to alkali stress.
AB  - KEY MESSAGE: An inorganic pyrophosphorylase gene, ThPP1 , modulated the
      accumulations of phosphate and osmolytes by up-regulating the differentially
      expression genes, thus enhancing the tolerance of the transgenic rice to alkali
      stress (AS). Inorganic pyrophosphorylase is essential in catalyzing the
      hydrolysis of pyrophosphate to inorganic phosphate during plant growth. Here, we
      report the changes of physiological osmolytes and differentially expression genes
      in the transgenic rice overexpressing a soluble inorganic pyrophosphatase gene
      ThPP1 of Thellungiella halophila in response to AS. Analyses showed that the
      ThPP1 gene was a PPase family I member which is located to the cytoplasm. Data
      showed that the transgenic lines revealed an enhanced tolerance to AS compared to
      the wild type, and effectively increased the accumulations of inorganic phosphate
      and organic small molecules starch, sucrose, proline and chlorophyll, and
      maintained the balance of osmotic potential by modulating the ratio of Na+/K+ in
      plant cells. Under AS, total 379 of differentially expression genes were up
      regulated in the leaves of the transgenic line compared with control, and the
      enhanced tolerance of the transgenic rice to the AS seemed to be associated with
      the up-regulations of the osmotic stress-related genes such as the L-type lectin
      domain containing receptor kinase (L-type LecRK), the cation/H+ antiporter gene
      and the vacuolar cation/proton exchanger 1 gene (CAX1), which conferred the
      involvements in the biosynthesis and metabolic pathways. Protein interaction
      showed that the ThPP1 protein specifically interacted with a 16# target partner
      of the photosystem II light-harvesting-Chl-binding protein. This study suggested
      that the ThPP1 gene plays an important regulatory role in conferring the
      tolerance of the transgenic rice to AS, and is an effective candidate in
      molecular breeding for crop cultivation of the alkali tolerance.

PMID- 29030651
TI  - Third symposium on Environmental Toxicology in North Rhine-Westphalia, Germany:
      Interdisciplinary Research Activities in Toxicology, Statistics, Hygiene and
      Medicine : Meeting report on a symposium held in Dortmund May 7-8, 2015.

PMID- 29030652
TI  - Evidence for a complex formation between CYP2J5 and mEH in living cells by FRET
      analysis of membrane protein interaction in the endoplasmic reticulum (FAMPIR).
AB  - The potential complex formation between microsomal epoxide hydrolase (mEH) and
      cytochrome P450-dependent monooxygenase (CYP) has been a subject of research for
      many decades. Such an association would enable efficient substrate channeling
      between CYP and mEH and as such represent an attractive strategy to prevent
      deleterious accumulation of harmful metabolic by-products such as CYP-generated
      epoxide intermediates. However, such complex formation is experimentally
      difficult to prove, because CYP and mEH are membrane-bound proteins that are
      prone to unspecific aggregation after solubilization. Here, we report the
      development of a FRET-based procedure to analyze the mEH-CYP interaction in
      living cells by fluorescence-activated cell sorting. With this non-invasive
      procedure, we demonstrate that CYP2J5 and mEH associate in the endoplasmic
      reticulum of recombinant HEK293 cells to the same extent as do CYP2J5 and its
      indispensible redox partner cytochrome P450 reductase. This presents final proof
      for a very close proximity of CYP and mEH in the endoplasmic reticulum,
      compatible with and indicative of their physical interaction. In addition, we
      provide with FAMPIR a robust and easy-to-implement general method for analyzing
      the interaction of ER membrane-resident proteins that share a type I topology.

PMID- 29030653
TI  - Lateral unicompartmental knee replacement: a systematic review of reasons for
      failure.
AB  - PURPOSE: Currently, individual studies lack the power to successively illustrate
      different failure modes; therefore, we undertook a systematic review to examine
      lateral unicompartmental knee replacement (lat UKR) failure modes. Furthermore,
      we compared early with midterm and late failures and fixed-bearing with mobile
      bearing implants. METHODS: A search using the databases of PubMed, EMBASE,
      Cochrane, and annual registries was performed to search for failed lat UKRs.
      Studies were included when they reported more than four failures, described
      failure modes and were minimum level IV studies. Data was analysed based on
      overall failure modes, fixed- vs. mobile bearing and early (<5 years) vs. midterm
      (5-10 years) vs. late failures (>10 years). RESULTS: Fourteen cohort studies and
      two registry-based studies were included. A total of 336 overall failures, 87
      time-dependent failures, and 175 implant-specific failures were identified. The
      main overall causes of failure were osteoarthritis (OA) progression (30%) and
      aseptic loosening (22%). These were followed by less common causes such as
      instability (7%), unexplained pain (5%), infection (5%), polyethylene wear (5%),
      and bearing dislocation (5%). Bearing dislocation was the most common early
      failure (29%) and also the most common failure among mobile-bearing implants
      (27%). In midterm and late failures, OA progression had the highest rates (59%
      and 78% respectively) and was also the most common type of failure in fixed
      bearing implants (44%). CONCLUSIONS: Progression of OA and aseptic loosening are
      the major overall failure modes in lat UKR. Bearing dislocation was the main
      failure mode in early years and in mobile-bearing implants, whereas OA
      progression caused most failures in late years and in fixed-bearing implants.
      LEVEL OF EVIDENCE: Systematic Review of minimum level IV studies.

PMID- 29030655
TI  - [Tendonitis calcarea of the piriformis muscle in a young amateur athlete].
AB  - Distinct calcific tendonitis associated with chronic pain refractory to
      conservative treatment can require operative treatment. Symptomatic calcific
      tendonitis of the piriform muscle, despite calcific tendonitis of other regions,
      is an extremely rare diagnosis. We report about a young athlete with persistent
      gluteal pain despite long-term conservative treatment. MRI scans revealed
      tendonitis calcarea with surrounding soft tissue inflammation. On open surgical
      removal of the calcification, pain symptoms were relieved and the patient was
      able to return to sports.

PMID- 29030656
TI  - [Pyoderma gangraenosum after implantation of a shoulder endoprothesis].
AB  - Pyoderma gangrenosum is an inflammatory, ulcerative, neutrophilic dermatosis that
      is clinically characterized by rapidly evolving, painful, necrotic skin lesions.
      It is typically associated with chronic systemic inflammatory or neoplastic
      diseases, but may also occur secondary to cutaneous injury or surgery (pathergy).
      Post-surgical pyoderma gangrenosum typically develops around surgical sites
      within the immediate postoperative period, mimicking early wound infection.
      However, common treatment strategies including antibiotics and debridement fail
      to improve or even worsen symptoms. Postoperative pyoderma gangrenosum has been
      most commonly reported from breast and visceral surgery. We present a case of
      postoperative pyoderma gangrenosum following total shoulder arthroplasty.

PMID- 29030654
TI  - Predictive and prognostic value of tumor volume and its changes during radical
      radiotherapy of stage III non-small cell lung cancer : A systematic review.
AB  - PURPOSE: Lung cancer remains the leading cause of cancer-related mortality
      worldwide. Stage III non-small cell lung cancer (NSCLC) includes heterogeneous
      presentation of the disease including lymph node involvement and large tumour
      volumes with infiltration of the mediastinum, heart or spine. In the treatment of
      stage III NSCLC an interdisciplinary approach including radiotherapy is
      considered standard of care with acceptable toxicity and improved clinical
      outcome concerning local control. Furthermore, gross tumour volume (GTV) changes
      during definitive radiotherapy would allow for adaptive replanning which offers
      normal tissue sparing and dose escalation. METHODS: A literature review was
      conducted to describe the predictive value of GTV changes during definitive
      radiotherapy especially focussing on overall survival. The literature search was
      conducted in a two-step review process using PubMed(r)/Medline(r) with the key
      words "stage III non-small cell lung cancer" and "radiotherapy" and "tumour
      volume" and "prognostic factors". RESULTS: After final consideration 17, 14 and 9
      studies with a total of 2516, 784 and 639 patients on predictive impact of GTV,
      GTV changes and its impact on overall survival, respectively, for definitive
      radiotherapy for stage III NSCLC were included in this review. Initial GTV is an
      important prognostic factor for overall survival in several studies, but the time
      of evaluation and the value of histology need to be further investigated. GTV
      changes during RT differ widely, optimal timing for re-evaluation of GTV and
      their predictive value for prognosis needs to be clarified. The prognostic value
      of GTV changes is unclear due to varying study qualities, re-evaluation time and
      conflicting results. CONCLUSION: The main findings were that the clinical impact
      of GTV changes during definitive radiotherapy is still unclear due to
      heterogeneous study designs with varying quality. Several potential confounding
      variables were found and need to be considered for future studies to evaluate GTV
      changes during definitive radiotherapy with respect to treatment outcome.

PMID- 29030657
TI  - Meloxicam and risk of myocardial infarction: a population-based nested case
      control study.
AB  - Certain non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with
      an increased risk of myocardial infarction (MI), a risk linked to cyclo-oxygenase
      2 inhibition. There are limited studies assessing the risk of MI associated with
      meloxicam, an increasingly popular drug with COX-2 inhibiting properties. A
      nested matched case-control study using The Health Improvement Network, a UK
      population-based database was conducted. NSAID users between 35 and 89 years of
      age with at least 1 year enrollment in the cohort were included. Incident MI
      cases were matched on age, sex, practice and event date with up to 4 controls.
      NSAID exposure was categorized as remote (between 60 days and 1 year), recent
      (between 1 and 60 days) or current relative to the event date. Current users were
      further classified as naproxen (negative control), diclofenac (positive control),
      meloxicam or other NSAID users. Multivariable conditional logistic regression was
      conducted to determine the risk of MI for each NSAID use categories compared with
      that of remote users. 9291 MI cases were matched with 30,676 controls. The cases
      had a higher prevalence of traditional cardiac risk factors, chronic kidney
      disease and inflammatory arthritis and cardioprotective drug utilization. The
      adjusted odds ratio of MI for current user compared to remote users were:
      meloxicam 1.38 (1.17-1.63), naproxen 1.12 (0.96-1.30) and diclofenac 1.37 (1.25
      1.50). In this large population-based study, meloxicam increased the risk of MI
      by 38%. This study warrants cautious use of this increasingly popular drug.

PMID- 29030658
TI  - Subgrouping fibromyalgia according to prevalence data may lead to a new
      therapeutic concept.

PMID- 29030659
TI  - Cyclophosphamide could be a better choice than methotrexate as induction
      treatment for patients with more severe Takayasu's arteritis.
AB  - To assess the effectiveness of cyclophosphamide (CYC) versus methotrexate (MTX)
      for active Takayasu's arteritis (TA). The current study was based on a cohort of
      TA at Zhongshan Hospital, Fudan University. TA was diagnosed using the 1990
      American College of Rheumatology criteria. Fifty-eight subjects receiving
      induction treatment with CYC (n = 46) or MTX (N = 12) were included in the
      analysis. Effectiveness and toxicity were assessed in all 58 cases. Clinical
      remission was defined as: Kerr score reduction to <= 1 and glucocorticoids (GC)
      treatment at a dose of <= 0.2 mg/kg/day (<= 15 mg/day) at the end of the 6th
      month. At the baseline, the CYC group had higher Kerr scores (60.9% vs. 16.7% at
      >=3, p = 0.044), higher ESR (55 +/- 52 vs. 25 +/- 22 mm/H, p = 0.048), ITAS_ESR
      (12.4 +/- 1.7 vs. 9.1 +/- 1.1 mg/L, p = 0.043). The 6-month clinical remission
      rate was 71.7% vs. 75% in the CYC and MTX group, respectively. In the CYC group,
      a significant decrease was observed in ESR (55 +/- 52 vs. 25 +/- 48 mm/H, p =
      0.008), hs-CRP (27 +/- 23 vs. 6.9 +/- 6.6 mg/L, p = 0.007), ITAS (11.7 +/- 2.2
      vs. 7.0 +/- 1.5, p = 0.048), and ITAS_ESR (7.1 +/- 2.0 vs. 12.4 +/- 1.7, p =
      0.033). However, no significant reductions in these measures were demonstrated in
      the MTX group. Whole-body contrast enhanced magnetic resonance angiography (MRA)
      revealed significant radiologic improvement (wall enhancement scores: 4.2 +/- 2.3
      vs. 10.3 +/- 3.8, p = 0.032) in the CYC group, but not in the MTX group. No
      severe adverse events occurred in any subject. Cyclophosphamide could be a better
      choice than methotrexate as induction treatment for patients with more severe
      Takayasu's arteritis.

PMID- 29030661
TI  - Identification of the major histocompatibility complex class-II DM and DO alleles
      in a cohort of northern pig-tailed macaques (Macaca leonina).
AB  - The northern pig-tailed macaque (Macaca leonina) has been considered as an
      independent species from the pig-tailed macaque group. We have previously
      reported that this species macaque has the potential to be a useful animal model
      in HIV/AIDS pathogenesis and vaccine studies due to its susceptibility to HIV-1.
      To develop this animal into a potential HIV/AIDS model, we have studied the
      classical MHC genes of this animal. In this study, the non-classical MHC genes
      Malo-DM and Malo-DO alleles were first characterized by sequencing and cloning in
      12 unrelated northern pig-tailed macaques. A total of 20 full-length sequences
      identified include 4 Malo-DMA, 5 Malo-DMB, 7 Malo-DOA, and 4 Malo-DOB alleles.
      Most of these allele sequences were shared between northern pig-tailed macaque
      and other macaque species in exon 2. The full-length MHC-DM and MHC-DO sequences
      provide more comprehensive analysis of immunogenetics of northern pig-tailed
      macaques and increase the value of the macaques in further biomedical studies.

PMID- 29030660
TI  - Tofacitinib improves atherosclerosis despite up-regulating serum cholesterol in
      patients with active rheumatoid arthritis: a cohort study.
AB  - Patients with rheumatoid arthritis (RA) have an increased cardiovascular (CV)
      risk. This study aimed to analyze the effects of Tofacitinib treatment, a Janus
      kinase inhibitor, on atherosclerosis in patients with RA. Patients with an active
      RA (28-joint disease activity score-erythrocyte sedimentation rate > 3.2) despite
      methotrexate (MTX) treatment 12 mg/week were included in this open-label
      prospective study and started on Tofacitinib (10 mg/day, 5 mg twice/day).
      Japanese guideline does not allow high dose of MTX. All patients used a stable
      dosage of MTX, steroids, and statins or lipid-lowering drugs. The primary
      endpoint was the comparison of the carotid intima-media thickness (CIMT) at the
      baseline and 54 weeks after Tofa treatment. Clinical data were collected at
      regular visits. Forty-six patients completed this study. CIMT did not
      significantly change from baseline to 54 weeks (1.09 +/- 0.69 and 1.08 +/- 0.78
      mm, p = 0.82). In 12 patients who had atherosclerosis at baseline (carotid intima
      media thickness > 1.10 mm), there was a significant decrease in CIMT (0.05+/-
      0.026 mm; p < 0.05). However, the decrease in CIMT was of limited clinical
      significance. Tofacitinib increased fasting total cholesterol levels from
      baseline to 54 weeks (216 +/- 25.3 and 234 +/- 28.8 mg/dL, p < 0.01). Tofacitinib
      affects atherosclerosis in patients with active RA The CIMT in RA patients was
      stable. Tofacitinib decreased the CIMT of patients who had increased CIMT at
      baseline. Tofacitinib reduced RA disease activity and limited vascular damage
      despite up-regulating cholesterol in patients with an active RA.

PMID- 29030662
TI  - Oral histone deacetylase inhibitor synergises with T cell targeted immunotherapy
      to preserve beta cell metabolic function and induce stable remission of new-onset
      autoimmune diabetes in NOD mice.
AB  - AIM/HYPOTHESIS: Combination therapy targeting the major actors involved in the
      immune-mediated destruction of pancreatic beta cells appears to be an
      indispensable approach to treat type 1 diabetes effectively. We hypothesised that
      the combination of an orally active pan-histone deacetylase inhibitor (HDACi:
      givinostat) with subtherapeutic doses of CD3 antibodies may provide ideal synergy
      to treat ongoing autoimmunity. METHODS: NOD mice transgenic for the human
      CD3epsilon (also known as CD3E) chain (NOD-huCD3epsilon) were treated for recent
      onset diabetes with oral givinostat, subtherapeutic doses of humanised CD3
      antibodies (otelixizumab, 50 MUg/day, 5 days, i.v.) or a combination of both
      drugs. Disease remission, metabolic profiles and autoreactive T cell responses
      were analysed in treated mice. RESULTS: We demonstrated that givinostat
      synergised with otelixizumab to induce durable remission of diabetes in 80% of
      recently diabetic NOD-huCD3epsilon mice. Remission was obtained in only 47% of
      mice treated with otelixizumab alone. Oral givinostat monotherapy did not reverse
      established diabetes but reduced the in situ production of inflammatory cytokines
      (IL-1beta, IL-6, TNF-alpha). Importantly, the otelixizumab + givinostat
      combination strongly improved the metabolic status of NOD-huCD3epsilon mice; the
      mice recovered the capacity to appropriately produce insulin, control
      hyperglycaemia and sustain glucose tolerance. Finally, diabetes remission induced
      by the combination therapy was associated with a significant reduction of
      insulitis and autoantigen-specific CD8+ T cell responses.
      CONCLUSIONS/INTERPRETATION: HDACi and low-dose CD3 antibodies synergised to
      abrogate in situ inflammation and thereby improved pancreatic beta cell survival
      and metabolic function leading to long-lasting diabetes remission. These results
      support the therapeutic potential of protocols combining these two drugs, both in
      clinical development, to restore self-tolerance and insulin independence in type
      1 diabetes.

PMID- 29030663
TI  - Extraction of microRNAs from biological matrices with titanium dioxide
      nanofibers.
AB  - MicroRNAs (miRNAs) are small RNAs that bind to mRNA targets and regulate their
      translation. A functional study of miRNAs and exploration of their utility as
      disease markers require miRNA extraction from biological samples, which contain
      large amounts of interfering compounds for downstream RNA identification and
      quantification. The most common extraction methods employ silica columns or the
      TRIzol reagent but give out low recovery for small RNAs probably due to their
      short strand lengths. Herein, we fabricated the titanium dioxide nanofibers using
      electrospinning to facilitate miRNA extraction and developed the optimal buffer
      conditions to improve miRNA recovery from biological matrices of cell lysate and
      serum. We found that our TiO2 fibers could obtain a recovery of 18.0 +/- 3.6% for
      miRNA fibers while carrying out the extraction in the more complex medium of cell
      lysate, much higher than the 0.02 +/- 0.0001% recovery from the commercial kit.
      The much improved extraction of miRNAs from our fibers could be originated from
      the strong coordination between TiO2 and RNA's phosphate backbone. In addition,
      the binding, washing, and elution buffers judiciously developed in the present
      study can achieve selective extraction of small RNA shorter than 500 nucleotides
      in length. Our results demonstrate that TiO2 nanofibers can work as a valuable
      tool for extraction of miRNAs from biological samples with high recovery.
      Graphical abstract Schematic for extraction of small RNAs using TiO2 nanofibers.

PMID- 29030664
TI  - SOFAST-HMQC-an efficient tool for metabolomics.
AB  - Nuclear magnetic resonance (NMR)-based metabolomics relies mostly on 1D NMR;
      however, the technique is limited by overlap of the signals from the metabolites.
      In order to circumvent this problem, 2D 1H-13C correlation spectroscopy
      techniques are often used. However owing to poorer natural abundance and
      gyromagnetic ratio of 13C, the acquisition time for 2D 1H-13C heteronuclear
      single quantum coherence spectroscopy (HSQC) is long. This makes it almost
      impossible to be used in high throughput study. We have reported the application
      of selective optimized flip angle short transient (SOFAST) technique coupled to
      heteronuclear multiple quantum correlation (HMQC) along with nonlinear sampling
      (NUS) in urine and serum samples. This technique takes sevenfold less
      experimental time than the conventional 1H-13C HSQC experiment with retention of
      almost all molecular information. Hence, this can be used for high throughput
      study. Graphical abstract SOFAST-HMQC is a two-dimensional NMR technique that
      significantly decreases experimental time without loss of information. This
      technique is applied in complex biofluid samples that are used for high
      throughput metabolomics studies and shows promise of better information recovery
      than conventional two-dimensional NMR technique in shorter time.

PMID- 29030665
TI  - Development and validation of a simple, rapid and sensitive LC-MS/MS method for
      the measurement of urinary neurotransmitters and their metabolites.
AB  - Neurotransmitters play crucial roles in physiological functions and their
      imbalances have demonstrated association in the pathology of several diseases.
      The measurement of neurotransmitters possesses a great potential as a significant
      clinical tool. This study presents the development and validation of an LC-MS/MS
      method for simultaneous quantification of multi-class neurotransmitters
      associated with dopamine, tryptophan and glutamate-gamma-aminobutyric acid
      pathways. A total of ten neurotransmitters and their metabolites (dopamine,
      epinephrine, metanephrine, tryptophan, serotonin, kynurenic acid, kynurenine,
      anthranilic acid, GABA, glutamic acid) were determined based on a simple and
      rapid 'dilute and shoot' method using minimal urine volume. The chromatographic
      separation was achieved using a Poroshell 120 Bonus-RP LC Column in combination
      with a gradient elution within an 8.5-min time frame. The method exhibited good
      sensitivity as the limits of quantification ranged between 0.025 and 0.075 MUg/mL
      with acceptable matrix effects (< +/- 14.5%), no carryover and good linearity (r
      2 > 0.98). The accuracy and precision for all analytes were within tolerances, at
      < +/- 9.9% mean relative error (MRE) and < 8.6% relative standard deviation
      (RSD), respectively. The method was successfully applied in measuring the
      neurotransmitter concentrations in urine of healthy donors. Furthermore, the
      undertaken stability experiments indicated that acidified urine specimens allowed
      the analytes to be stable for prolonged durations in comparison to those
      untreated. The study also reveals the performance of the method is unaffected by
      the absence of expensive deuterated reference standards under the experimental
      conditions employed which further simplifies the analytical procedures and
      provides a significant cost saving for running the assay. Graphical abstract The
      quantification of multi-class neurotransitters associated with the dopamine,
      tryptophan and GABA-glutamate pathways using a simple 'dilute and shoot' LC-MS/MS
      method.

PMID- 29030666
TI  - LC-PDA/APCIitMS identification of algal carotenoid and oxysterol precursors to
      fatty acid esters in hydrolyzed extracts of the freshwater mussel Dreissena
      bugensis.
AB  - Carotenyl fatty acid esters (carotenyl-FAEs) were extracted in acetone from
      freeze-dried Dreissena bugensis (Lakes Erie and Ontario) and hydrolyzed to
      identify the carotenoid precursors. Analysis by liquid chromatography (LC) with
      photodiode array (PDA) and atmospheric pressure chemical ionization-ion trap mass
      spectrometry (APCIitMS) revealed the major hydrolysis products: fucoxanthinol
      (FOH) from fucoxanthin (FX, diatoms); mactraxanthin (MX) from violaxanthin (VX,
      chlorophytes); 4-fold higher levels of an unknown, tentatively identified as an
      adduct of two closely eluting C27H46O3 and C27H48O3 steryl triols. Enzymatic
      hydrolysis (Candida rugosa) of dreissenid extracts yielded FOH and MX, but
      residual carotenyl-FAEs remained. Alkaline hydrolysis yielded isoFOH, MX, and
      steryl triols, without residual carotenyl-FAEs: isoFOH decreased, but two FOH
      hemiketal by-products increased, when the dose of potassium hydroxide in methanol
      was too high. The PDA detector profiled carotenyl-FAEs and products of enzymatic
      and alkaline hydrolysis, without interference. The APCIitMS detector revealed
      carotenoid and oxysterol products of alkaline hydrolysis but was adversely
      affected by background from bile salts used for enzymatic hydrolysis. LC
      retention times and elution order were correlated to solubility parameters,
      calculated from the analyte structure, to cross-check MS interpretations. A
      multiple linear regression of LC retention times on solubility parameters for 12
      carotenoid standards included FOH, isoFOH, and MX (r 2 0.97). The model revealed
      the close similarity of polar carotenoid metabolites to C27-steryl triols
      tentatively identified by APCIitMS, suggesting that further LC-MS analyses would
      be beneficial, to explicitly link oxysterols and the polar carotenoids, as
      metabolites of algal precursors in the dreissenid diet. Graphical abstract
      Methods of analysis and major neutral products of hydrolysis from fatty acid
      esters in D. bugensis.

PMID- 29030667
TI  - Sampling and analyte enrichment strategies for ambient mass spectrometry.
AB  - Ambient mass spectrometry provides great convenience for fast screening, and has
      showed promising potential in analytical chemistry. However, its relatively low
      sensitivity seriously restricts its practical utility in trace compound analysis.
      In this review, we summarize the sampling and analyte enrichment strategies
      coupled with nine modes of representative ambient mass spectrometry (desorption
      electrospray ionization, paper vhspray ionization, wooden-tip spray ionization,
      probe electrospray ionization, coated blade spray ionization, direct analysis in
      real time, desorption corona beam ionization, dielectric barrier discharge
      ionization, and atmospheric-pressure solids analysis probe) that have
      dramatically increased the detection sensitivity. We believe that these advances
      will promote routine use of ambient mass spectrometry. Graphical abstract Scheme
      of sampling stretagies for ambient mass spectrometry.

PMID- 29030668
TI  - Desktop NMR spectroscopy for real-time monitoring of an acetalization reaction in
      comparison with gas chromatography and NMR at 9.4 T.
AB  - Monitoring of chemical reactions in real-time is in demand for process control.
      Different methods such as gas chromatography (GC), mass spectroscopy, infrared
      spectroscopy, and nuclear magnetic resonance (NMR) are used for that purpose. The
      current state-of-the-art compact NMR systems provide a useful method to employ
      with various reaction conditions for studying chemical reactions inside the fume
      hood at the chemical workplace. In the present study, an acetalization reaction
      was investigated with compact NMR spectroscopy in real-time. Acetalization is
      used for multistep synthesis of the variety of organic compounds to protect
      particular chemical groups. A compact 1 T NMR spectrometer with a permanent
      magnet was employed to monitor the acid catalyzed acetalization of the p
      nitrobenzaldehyde with ethylene glycol. The concentrations of both reactant and
      product were followed by peak integrals in single-scan 1H NMR spectra as a
      function of time. The reaction conditions were varied in terms of temperature,
      agitation speed, catalyst loading, and feed concentrations in order to determine
      the activation energy with the help of a pseudo-homogeneous kinetic model. For
      low molar ratios of aldehyde and glycol, the equilibrium conversions were lower
      than for the stoichiometric ratio. Increasing catalyst concentration leads to
      faster conversion. The data obtained with low-field NMR spectroscopy were
      compared with data from GC and NMR spectroscopy at 9.4 T acquired in batch mode
      by extracting samples at regular time intervals. The reaction kinetics followed
      by either method agreed well. The activation energies for forward and backward
      reactions were determined by real-time monitoring with compact NMR at 1 T were 48
      +/- 5 and 60 +/- 4 kJ/mol, respectively. The activation energies obtained with
      gas chromatography for forward and backward reactions were 48 +/- 4 and 51 +/- 4
      kJ/mol. The equilibrium constant decreases with increasing temperature as
      expected for an exothermic reaction. The impact of dense sampling with online NMR
      and sparse sampling with GC was observed on the kinetic outcome using the same
      kinetic model. Graphical abstract Acetalization reaction kinetics were monitored
      with real-time desktop NMR spectroscopy at 1 T. Each data point was obtained at
      regular intervals with a single shot in 15 s. The kinetics was compared with
      sparsely sampled data obtained with GC and NMR at 9.4 T.

PMID- 29030669
TI  - Sol-gel-based SPME fiber as a reliable sampling technique for studying biogenic
      volatile organic compounds released from Clostridium tetani.
AB  - A novel and efficient headspace solid-phase microextraction (HS-SPME) method,
      followed by gas chromatography mass spectrometry (GC-MS), was developed to study
      volatile organic compounds (VOCs) emerging from microorganisms. Two homemade SPME
      fibers, a semi-polar poly (dimethylsiloxane) (PDMS) fiber, and a polar
      polyethylene glycol (PEG) fiber, along with two commercial fibers (PDMS and
      PDMS/DVB) were used to collect VOCs emerging from Clostridium tetani which was
      cultured in different media. The adsorbed VOCs were desorbed and identified, in
      vitro, using GC-MS. The adsorption efficiency was improved by optimizing the time
      duration of adsorption and desorption. About 50 components were identified by the
      proposed method. The main detected compounds appeared to be sulfur containing
      compounds such as butanethioic acid S-methyl ester, dimethyl trisulfide, and
      dimethyl tetrasulfide. These volatile sulfur containing compounds are derived
      from amino acids containing the sulfur element, which probably coexist in the
      mentioned bacterium or are added to the culture media. The developed HS-SPME-GC
      MS method allowed the determination of the chemical fingerprint of Clostridium
      tetani volatile constituents, and thus provides a new, simple, and reliable tool
      for studying the growth of microorganisms. Graphical abstract Investigation of
      biogenic VOCs released from Clostridium tetani using SPME-GC-MS.

PMID- 29030670
TI  - Ultra-high-performance supercritical fluid chromatography with quadrupole-time-of
      flight mass spectrometry (UHPSFC/QTOF-MS) for analysis of lignin-derived
      monomeric compounds in processed lignin samples.
AB  - The conversion of lignin to potentially high-value low molecular weight compounds
      often results in complex mixtures of monomeric and oligomeric compounds. In this
      study, a method for the quantitative and qualitative analysis of 40 lignin
      derived compounds using ultra-high-performance supercritical fluid chromatography
      coupled to quadrupole-time-of-flight mass spectrometry (UHPSFC/QTOF-MS) has been
      developed. Seven different columns were explored for maximum selectivity. Makeup
      solvent composition and ion source settings were optimised using a D-optimal
      design of experiment (DoE). Differently processed lignin samples were analysed
      and used for the method validation. The new UHPSFC/QTOF-MS method showed good
      separation of the 40 compounds within only 6-min retention time, and out of
      these, 36 showed high ionisation efficiency in negative electrospray ionisation
      mode. Graphical abstract A rapid and selective method for the quantitative and
      qualitative analysis of 40 lignin-derived compounds using ultra-high-performance
      supercritical fluid chromatography coupled to quadrupole-time-of-flight mass
      spectrometry (UHPSFC/QTOF-MS).

PMID- 29030671
TI  - Graphene-based label-free electrochemical aptasensor for rapid and sensitive
      detection of foodborne pathogen.
AB  - Reduced graphene oxide (rGO) has emerged as a promising nanomaterial for reliable
      detection of pathogenic bacteria due to its exceptional properties such as
      ultrahigh electron transfer ability, large surface to volume ratio,
      biocompatibility, and its unique interactions with DNA bases of the aptamer. In
      this study, rGO-azophloxine (AP) nanocomposite aptasensor was developed for a
      sensitive, rapid, and robust detection of foodborne pathogens. Besides providing
      an excellent conductive and soluble rGO nanocomposite, the AP dye also acts as an
      electroactive indicator for redox reactions. The interaction of the label-free
      single-stranded deoxyribonucleic acid (ssDNA) aptamer with the test organism,
      Salmonella enterica serovar Typhimurium (S. Typhimurium), was monitored by
      differential pulse voltammetry analysis, and this aptasensor showed high
      sensitivity and selectivity for whole-cell bacteria detection. Under optimum
      conditions, this aptasensor exhibited a linear range of detection from 108 to 101
      cfu mL-1 with good linearity (R 2 = 0.98) and a detection limit of 101 cfu mL-1.
      Furthermore, the developed aptasensor was evaluated with non-Salmonella bacteria
      and artificially spiked chicken food sample with S. Typhimurium. The results
      demonstrated that the rGO-AP aptasensor possesses high potential to be adapted
      for the effective and rapid detection of a specific foodborne pathogen by an
      electrochemical approach. Graphical abstract Fabrication of graphene-based
      nanocomposite aptasensor for detection of foodborne pathogen.

PMID- 29030672
TI  - Interference-free determination of sub ng kg-1 levels of long-lived 93Zr in the
      presence of high concentrations (MUg kg-1) of 93Mo and 93Nb using ICP-MS/MS.
AB  - Long-lived high abundance radionuclides are of increasing interest with regard to
      decommissioning of nuclear sites and longer term nuclear waste storage and
      disposal. In many cases, no routine technique is available for their measurement
      in nuclear waste and low-level (ng kg-1) environmental samples. Recent advances
      in ICP-MS technology offer attractive features for the selective and sensitive
      determination of a wide range of long-lived radionuclides. In this work,
      inductively coupled plasma-tandem mass spectrometry (ICP-MS/MS)-based
      methodology, suitable for accurate routine determinations of 93Zr at very low (ng
      kg-1) levels in the presence of high levels (MUg kg-1) of the isobaric
      interferents 93Nb and 93Mo (often present in nuclear waste samples), is reported
      for the first time. Additionally, a novel and systematic strategy for method
      development based on the use of non-radioactive isotopes is proposed. It relies
      on gas-phase chemical reactions for different molecular ion formation to achieve
      isobaric interference removal. Using cell gas mixtures of NH3/He/H2 or H2/O2, and
      suitable mass shifts, the signal from the 93Nb and 93Mo isobaric interferences on
      93Zr were suppressed by up to 5 orders of magnitude. The achieved limit of
      detection for 93Zr was 1.3 * 10-5 Bq g-1 (equivalent to 0.14 ng kg-1). The sample
      analysis time is 2 min, which represents a significant improvement in terms of
      sample throughput, compared to liquid scintillation counting methods. The method
      described here can be used for routine measurements of 93Zr at environmentally
      relevant levels. It can also be combined with radiometric techniques for use
      towards the standardisation of 93Zr measurements. Graphical abstract Interference
      free determination of 93Zr in the presence of high concentrations of isobaric
      93Mo and 93Nb by ICP-MS/MS.

PMID- 29030673
TI  - PRIMUM NON NOCERE: now and again an echo of DPD with capecitabine.

PMID- 29030674
TI  - Magnetic Resonance Neurography : Normal Values and Demographic Determinants of
      Nerve Caliber and T2 Relaxometry in 60 healthy individuals.
AB  - PURPOSE: To establish normal values and to identify demographic determinants of
      quantitative biomarkers in magnetic resonance neurography (MRN). METHODS: In this
      study 60 healthy individuals (5 men and 5 women of every decade between 20 and 80
      years) were examined according to a standardized MRN protocol at 3 T, including
      multiecho T2 relaxometry. Nerve cross-sectional area (CSA), transverse relaxation
      time (T2), and proton spin density (PSD) were assessed for the sciatic, tibial,
      median, ulnar, and radial nerves. Correlation with demographic variables, such as
      height, weight, body mass index (BMI), and age was expressed by Pearson
      coefficients and t-tests were used to compare MRN biomarkers between men and
      women with and without normalization to body weight and BMI by linear regression.
      RESULTS: The average nerve CSA correlated moderately with height (r = 0.28, p =
      0.04), weight (r = 0.40, p = 0.002), and BMI (r = 0.35, p = 0.008), but not with
      age (r = 0.23, p = 0.09). While T2 did not correlate with demographic parameters,
      PSD was strongly inversely associated with BMI (r = -0.64, p < 0.001) and weight
      (r = -0.557, p < 0.001). Sex-dependent differences in imaging marker values were
      found for CSA but became negligible after normalization to body weight.
      CONCLUSION: Quantitative biomarkers of MRN co-vary with demographic variables. As
      particularly important determinants, we identified body weight for nerve CSA and
      BMI for PSD. The presented normal values and demographic determinants may assist
      investigations into the potential of MRN biomarkers in further disease-specific
      studies.

PMID- 29030675
TI  - Evaluation of Prognostic Factors for Esophageal Squamous Cell Carcinoma Treated
      with Neoadjuvant Chemoradiotherapy Followed by Surgery.
AB  - BACKGROUND: Intensive trimodality therapy is needed for locally advanced
      esophageal squamous cell carcinoma (ESCC). However, some patients develop
      recurrence and die of cancer even after trimodality therapy. METHODS: We
      evaluated prognostic factors based on data from 125 patients with ESCC who
      underwent neoadjuvant chemoradiotherapy (NCRT) comprising concurrent chemotherapy
      and 40 Gy of radiation, followed by curative-intent esophagectomy. RESULTS:
      Thirty-four (27.2%) patients achieved a pathological complete response (pCR)
      after NCRT. The 5-year recurrence-free (RFS) and overall survival (OS) rates of
      all patients were 49.2 and 52.9%, respectively, and were significantly better for
      patients with pCR than without pCR (p = 0.01 and 0.02, respectively). Univariate
      and multivariate analyses selected performance status [PS 0 vs. 1: hazard ratio
      (HR) 2.05; 95% confidence interval (CI) 1.30-4.84; p = 0.01] and ypN (0 vs. 1: HR
      2.33; 95% CI 1.12-4.84; p = 0.02; 0 vs. 2/3: HR 3.73; 95% CI 1.68-8.28; p =
      0.001) as independent covariates for RFS. Furthermore, PS (0 vs. 1; HR 2.94; 95%
      CI 1.51-5.72; p = 0.002) and ypN (0 vs. 1; HR 2.26; 95% CI 1.09-4.69; p = 0.03; 0
      vs. 2/3: HR 3.90; 95% CI 1.79-8.48; p = 0.001) were also independent covariates
      for OS. CONCLUSIONS: Performance status 1 and ypN+ were significantly associated
      with a poor prognosis after trimodality therapy for ESCC.

PMID- 29030676
TI  - Papillary Thyroid Carcinoma (PTC) in Children and Adults: Comparison of Initial
      Presentation and Long-Term Postoperative Outcome in 4432 Patients Consecutively
      Treated at the Mayo Clinic During Eight Decades (1936-2015).
AB  - BACKGROUND: Contemporary guidelines for managing PTC advise an approach wherein
      primary tumor and regional metastases (RM) are completely resected at first
      surgery and radioiodine remnant ablation (RRA) is restricted to high-risk
      patients, policies our group has long endorsed. To assess our therapeutic
      efficacy, we studied 190 children and 4242 adults consecutively treated during
      1936-2015. SUBJECTS AND METHODS: Mean follow-up durations for children and adults
      were 26.9 and 15.2 years, respectively. Bilateral lobar resection was performed
      in 86% of children and 88% of adults, followed by RRA in 30% of children and 29%
      of adults; neck nodes were excised in 86% of children and 66% of adults. Tumor
      recurrence (TR) and cause-specific mortality (CSM) details were taken from a
      computerized database. RESULTS: Children, when compared to adults, had larger
      primary tumors which more often were grossly invasive and incompletely resected.
      At presentation, children, as compared to adults, had more RM and distant
      metastases (DM). Thirty-year TR rates were no different in children than adults
      at any site. Thirty-year CSM rates were lower in children than adults (1.1 vs.
      4.9%; p = 0.01). Comparing 1936-1975 (THEN) with 1976-2015 (NOW), 30-year CSM
      rates were similar in MACIS <6 children (p = 0.67) and adults (p = 0.08).
      However, MACIS <6 children and adults in 1976-2015 had significantly higher
      recurrence at local and regional, but not at distant, sites. MACIS 6+ adults,
      NOW, compared to THEN, had lower 30-year CSM rates (30 vs. 47%; p < 0.001),
      unassociated with decreased TR at any site. CONCLUSIONS: Children, despite
      presenting with more extensive PTC when compared to adults, have postoperative
      recurrences at similar frequency, typically coexist with DM and die of PTC less
      often. Since 1976, both children and adults with MACIS <6 PTC have a <1% chance
      at 30 years of CSM; adults with higher MACIS scores (6 or more) have a 30-year
      CSM rate of 30%.

PMID- 29030677
TI  - Safe Surgery for All: Early Lessons from Implementing a National Government
      Driven Surgical Plan in Ethiopia.
AB  - Recognizing the unmet need for surgical care in Ethiopia, the Federal Ministry of
      Health (FMOH) has pioneered innovative methodologies for surgical system
      development with Saving Lives through Safe Surgery (SaLTS). SaLTS is a national
      flagship initiative designed to improve access to safe, essential and emergency
      surgical and anaesthesia care across all levels of the healthcare system.
      Sustained commitment from the FMOH and their recruitment of implementing partners
      has led to notable accomplishments across the breadth of the surgical system,
      including but not limited to: (1) Leadership, management and governance-a
      nationally scaled surgical leadership and mentorship programme, (2)
      Infrastructure-operating room construction and oxygen delivery plan, (3) Supplies
      and logistics-a national essential surgical procedure and equipment list, (4)
      Human resource development-a Surgical Workforce Expansion Plan and Anaesthesia
      National Roadmap, (5) Advocacy and partnership-strong FMOH partnership with
      international organizations, including GE Foundation's SafeSurgery2020
      initiative, (6) Innovation-facility-driven identification of problems and
      solutions, (7) Quality of surgical and anaesthesia care service delivery-a
      national peri-operative guideline and WHO Surgical Safety Checklist
      implementation, and (8) Monitoring and evaluation-a comprehensive plan for short
      term and long-term assessment of surgical quality and capacity. As Ethiopia
      progresses with its commitment to prioritize surgery within its Health Sector
      Transformation Plan, disseminating the process and outcomes of the SaLTS
      initiative will inform other countries on successful national implementation
      strategies. The following article describes the process by which the Ethiopian
      FMOH established surgical system reform and the preliminary results of
      implementation across these eight pillars.

PMID- 29030678
TI  - Clock-Drawing Test as a Bedside Assessment of Post-operative Delirium Risk in
      Elderly Patients with Accidental Hip Fracture.
AB  - BACKGROUND: Currently applied cognitive tests for assessing the risk of post
      operative delirium require time and specialised medical staff, in addition to the
      patients' mental strain. We investigated the four-point scoring Clock-Drawing
      Test (CDT-4) as a preoperative independent predictor for post-operative delirium.
      METHODS: A total of 100 consecutive patients aged over 65 years admitted for
      accidental hip fracture were assessed for delirium using the Confusion Assessment
      Method Scale. The cognitive function was rated with mini-mental state
      examination, Montreal Cognitive Assessment Scale (MoCA), and CDT-4. Descriptive
      statistics were performed, and a logistic regression model for post-operative
      delirium was applied. RESULTS: Out of the 100 enrolled patients 98 underwent hip
      repair surgery and 65 (66%) had post-operative delirium, with 24 (42%) incident
      cases. The median (IQR) ages were 78 (72-83) and 84 (80-87) years for the non
      delirium and post-operative delirium groups, respectively. The logistic
      regression concluded with age and CDT-4 as independent preoperative predictors,
      while controlling for gender, pre-surgery delirium, MoCA visual, and MoCA
      attention: OR 1.32 [95% CI (1.099-1.585); p = 0.003] for age; OR 0.153 [95% CI
      (0.033-0.719); p = 0.017] for CDT-4. CONCLUSIONS: Employing CDT-4 as a bedside
      assessment of delirium risk may help to preoperatively stratify and prioritise
      the patients for preventive perioperative care in a timely manner.

PMID- 29030679
TI  - Correction to: A Global Assessment of Access to and Use of Medical Information:
      The State of Evidence-Based Surgery.
AB  - In the original article some funding information was inadvertently omitted. The
      complete funding information is as follows.

PMID- 29030680
TI  - [Modern non-cosmetic treatment with botulinum toxins].
AB  - Botulinum toxin has been known in medical history for a long time. The first
      scientific investigations and thoughts on possible indications in the treatment
      of muscular disorders were published by the German physician and poet Justinus
      Kerner in 1822. The physiological effect of botulinum toxin was identified in the
      middle of the twentieth century and the first clinical use was reported in 1977.
      It was first used in ophthalmology for the correction of strabismus and some
      years later the therapy of blepharospasm and cervical dystonia was established.
      Further indications, all supported by randomized controlled studies, are spastic
      tone increase of the limbs after lesions of the central nervous system,
      idiopathic axillar hyperhidrosis, chronic migraine and neurogenic or idiopathic
      bladder hyperactivity. In addition to these indications, a large number of
      further possible options have been published in the literature. Beside its effect
      on transmission at the neuromuscular synapses, botulinum toxin has also been
      shown to affect the sensory transmission of nociceptive fibers.

PMID- 29030683
TI  - Preoperative alkaline phosphatase elevation was associated with poor survival in
      colorectal cancer patients.
AB  - PURPOSE: Purpose To assess preoperative serum alkaline phosphatase (ALP) levels
      in colon adenocarcinomapatients with various clinical features and determine its
      prognostic value. METHODS: Between 2000 and 2013, 10,800 stage I-IV colon cancer
      patients who underwent surgery wereretrospectively enrolled. The relationship
      between ALP level and variables, including age, gender,carcinoembryonic Antigen
      (CEA) levels, aspartate aminotransferase (AST) level, bilirubin level, tumor
      size,liver cirrhosis, hepatitis, albumin level, histological type, and TNM-stage,
      were evaluated. The impact of ALP level elevation on survival was evaluated.
      RESULTS: Significant elevations in ALP level were found in patients with CEA >=5
      ng/ml (p<0.001); AST |>=43 U/L (p<0.001); total bilirubin >=1.5 U/L (p<0.001);
      liver cirrhosis (p<0.001); albumin; <3.5g/dL (p <0.001); and stage IV disease
      (p=0.03).Patients with elevated ALP levels had significantly worse 5-year overall
      survival (OS) for colon (5-year OSrate: 71.5% vs. 78.3%, p<0.001; Fig. 1a) and
      rectal (5-year OS rate: 64.5% vs. 72.3%, p<0.001; Fig. 1b)cancer than patients
      with normal ALP levels. CONCLUSIONS: Elevated preoperative ALP levels was not
      only associated with liver disease, but it was alsorelated with advanced tumor
      status, and indicated a poor survival in colon and rectal cancer patients.

PMID- 29030684
TI  - [Prevention of falls and fall-related injuries : Personal balance and future
      tasks].

PMID- 29030685
TI  - Combined effects of varicocele and cell phones on semen and hormonal parameters.
AB  - BACKGROUND: The objective of this study was to evaluate if there is a combined
      effect of varicocele and cell phone storage in trousers pockets on semen and
      hormonal parameters. METHODS: A retrospective analysis of 468 men attending an
      infertility clinic from 1993-2007 was performed. Varicoceles were determined by
      clinical examination and patients were questioned on cell phone usage and storage
      fashion. Semen samples were analyzed according to the World Health Organization
      (WHO) guidelines of 1999. Serum testosterone, luteinizing hormone (LH) and
      follicle stimulating hormone (FSH) were assessed. RESULTS: There was a
      significant effect of cell phone storage in trousers pockets and varicocele in
      multivariate analysis (both p < 0.001). Varicocele showed an effect on sperm
      concentration (p = 0.003), LH (p = 0.014) and testosterone (p = 0.003). Compared
      to grade 1, grade 2 varicoceles showed a difference in sperm concentration (p =
      0.004). Regarding testosterone differences were shown for grade 3 versus grade 1
      (p = 0.002) and grade 3 compared to grade 2 (p = 0.003). Cell phone storage in
      trousers pockets showed an influence on the percentage of normal sperm morphology
      and LH (both p < 0.001). Varicocele and cell phone storage in trousers pockets
      did not show a combined effect (p = 0.76). CONCLUSIONS: This analysis showed an
      inverse relation between sperm concentration and degree of varicocele, with lower
      concentrations in higher grade varicoceles. Testosterone was significantly higher
      in higher grade varicoceles, which could reflect a compensatory mechanism to the
      impaired testicular function. Cell phone storage in trousers pockets showed an
      effect on LH and sperm morphology. A combined effect of varicocele and cell phone
      storage in trousers pockets was not detected.

PMID- 29030686
TI  - Blood mercury concentration in relation to metabolic and weight phenotypes using
      the KNHANES 2011-2013 data.
AB  - PURPOSE: We assessed the association of blood mercury concentration with
      metabolic and weight phenotypes. METHODS: Blood mercury concentration, metabolic
      syndrome components, and body mass index (BMI) were measured in 6006 Korean
      adults (2963 men, 3043 women, mean age 44.7 +/- 14.7 years), using the 2011-2013
      Korean National Health and Nutrition Examination Survey data. Metabolic and
      weight phenotypes were classified based on BMI and metabolic syndrome (MetS)
      presence as metabolically healthy and normal weight (MHNW), metabolically
      unhealthy and normal weight (MUNW), metabolically healthy and obese (MHO), and
      metabolically unhealthy and obese (MUO). RESULTS: The geometric mean of blood
      mercury concentration was 3.37 MUg/L (95% CI 3.32-3.43). A higher quartile of
      blood mercury concentration was associated with older age, male sex, higher
      education, alcohol use, current smoking, low physical activity, greater energy
      intake, and hypertension history. After adjusting for confounding factors (age,
      sex, education, income, health behaviors, and energy intake), blood mercury
      concentration tended to increase across the MHNW, MUNW, MHO, and MUO groups in
      all subjects and each sex (P for trend < 0.01). Compared to the lowest mercury
      quartile group, adjusted odds ratios (95% CI) for MHO and MUO in those with the
      highest mercury quartile were, respectively, 1.67 (1.34, 2.09) and 2.02 (1.59,
      2.56) in all subjects: 1.58 (1.25, 1.99) and 1.72 (1.37, 2.16) for men; 1.33
      (0.94, 1.88) and 1.90 (1.34, 2.70) for women. CONCLUSIONS: Blood mercury
      concentration was associated with both metabolic syndrome and obesity, and the
      association was dose dependent across metabolic and weight phenotypes.

PMID- 29030687
TI  - Tolerability of Bisoprolol on Domiciliary Spirometry in COPD.
AB  - We investigated if serial domiciliary measures of spirometry were sensitive at
      detecting subtle effects of beta-2 blockade associated with bisoprolol in (n =
      17) patients with COPD. After a two-week run in on inhaled corticosteroid (ICS)
      and long acting beta-2 agonist (LABA): beclometasone/formoterol 100/6 ug,
      patients' started additional a long acting muscarinic receptor antagonist: (LAMA)
      Tiotropium 18 ug, with concomitant weekly dose titration of bisoprolol: 1.25-2.5
      5 mg. After a further week of bisoprolol 5 mg, they were stepped back down to
      (ICS/LABA) for one week. Mean age was 64 years, mean FEV1 52% predicted, and mean
      FEV1/FVC ratio of 0.46. Compared to baseline am FEV1 of 1.38 L (95% CI 1.14-1.61
      L), both ICS/LABA/LAMA and ICS/LABA in conjunction with bisoprolol showed
      statistically significant mean falls of 100 ml (1.28 L, 95% CI 1.03-1.53 L), and
      120 ml, respectively (1.26 L, 95% CI 1.01-1.51 L); equalling and exceeding the
      MCID of 100 ml, respectively. These changes were disconnected from symptoms,
      reliever use and oxygen saturation.

PMID- 29030689
TI  - The neurological outcome of radiotherapy versus surgery in patients with
      metastatic spinal cord compression presenting with myelopathy.
AB  - PURPOSE: While radiotherapy is generally an acceptable treatment for metastatic
      spinal cord compression, surgical intervention is controversial due to the
      invasiveness and diversity of diseases in the patients being considered. The
      ideal treatment, therefore, depends on the situation, and the most acute
      treatment possible is necessary in patients presenting with myelopathy. We
      compared the neurological outcomes between radiotherapy and surgery in patients
      with metastatic spinal cord compression presenting with myelopathy. METHODS: A
      total 54 patients with metastatic spinal cord compression presenting with
      myelopathy treated in our institution between 2006 and 2016 were analyzed
      retrospectively. Twenty patients were selected by radiotherapy alone (radiation
      group), and 36 patients were selected by decompression and stabilization surgery
      with or without radiotherapy (surgery group). The neurological outcomes and
      complications were compared between the two treatment groups. RESULTS: Seven
      patients initially in the radiation group underwent surgery because of a
      substantial decline in their motor strength during radiotherapy. One of the
      remaining 13 patients (8%) in the radiation group and 30 of the 34 patients (88%)
      in the surgery group showed improvement in their neurological symptoms (P <
      0.01). One patient (8%) in the radiation group and 21 patients (62%) in the
      surgery group were ambulatory after treatment (P < 0.01). There were no major
      complications related to radiotherapy, but surgery-related complications occurred
      in 9 of 34 (26%) patients, and 6 (18%) patients needed reoperation. CONCLUSIONS:
      Surgical decompression and stabilization may be required to improve the
      neurological function in patients with metastatic spinal cord compression
      presenting with myelopathy. However, the high rate of complications associated
      with surgery should be taken into consideration.

PMID- 29030690
TI  - Michelangelo Gangemi (1949-2017).

PMID- 29030688
TI  - Neurotrophic function of phytochemicals for neuroprotection in aging and
      neurodegenerative disorders: modulation of intracellular signaling and gene
      expression.
AB  - Bioactive compounds in food and beverages have been reported to promote health
      and prevent age-associated decline in cognitive, motor and sensory activities,
      and emotional function. Phytochemicals, a ubiquitous class of plant secondary
      metabolites, protect neuronal cells by interaction with cellular activities, in
      addition to the antioxidant and anti-inflammatory function. In aging and age
      associated neurodegenerative disorders, phytochemicals protect neuronal cells by
      neurotrophic factor-mimic activity, in addition to suppression of apoptosis
      signaling in mitochondria. This review presents the cellular mechanisms
      underlying anti-apoptotic function and neurotrophic function of phytochemicals in
      the brain. Phytochemicals bind to receptors of neurotrophic factors, and also
      receptors for gamma-aminobutyric acid, acetylcholine, serotonin, and glutamate
      and estrogen, and activate downstream signal pathways. Phytochemicals also
      directly intervene intracellular signaling molecules to modify the brain
      function. Finally, phytochemicals enhance the endogenous biosynthesis of genes
      coding anti-apoptotic Bcl-2 and neurotrophic factors, such as brain-derived and
      glial cell line-derived neurotrophic factor. The gene induction may play a major
      role in the neuroprotective function of dietary compounds shown by
      epidemiological studies. Quantitative measurement of neurotrophic factors induced
      by phytochemicals in the serum, cerebrospinal fluid, and other clinical samples
      is proposed as a surrogate assay method to evaluate the neuroprotective potency.
      Development of novel neuroprotective compounds is expected among compounds
      chemically synthesized from the brain-permeable basic structure of
      phytochemicals.

PMID- 29030692
TI  - Changes in aqueous concentrations of various cytokines after intravitreal
      bevacizumab and subtenon triamcinolone injection for diabetic macular edema.
AB  - PURPOSE: The purpose of this study was to compare the changes in the aqueous
      cytokine levels after intravitreal bevacizumab with those after combined
      intravitreal bevacizumab and subtenon triamcinolone injection in diabetic macular
      edema (DME). METHODS: This study examined 24 eyes of 23 patients with DME. Each
      patient with DME received randomly either an intravitreal injection of
      bevacizumab (IVBe) or IVBe with a subtenon triamcinolone injection (IVBe + STTA).
      Best corrected visual acuity and foveal thickness were evaluated and aqueous
      samples were obtained before and 4 weeks after the injection. The aqueous
      concentrations of interleukin (IL)-6, IL-8, interferon-induced protein (IP)-10,
      monocyte chemotactic protein (MCP)-1, platelet-derived growth factor (PDGF)-AA,
      and vascular endothelial growth factor (VEGF) were measured using a multiplex
      bead assay. RESULTS: After the injection, the foveal thickness decreased more in
      the IVBe + STTA group than in the IVBe group (P = 0.042). The MCP-1, PDGF-AA, and
      VEGF levels decreased significantly in the IVBe + STTA group (p = 0.013, p =
      0.004 and p = 0.018 respectively), but only the VEGF level decreased in the IVBe
      group (p = 0.001). IL-8 was significantly increased in the IVBe + STTA group (p =
      0.003) but the changes in the VEGF levels were smaller than in the IVBe group (p
      = 0.025). CONCLUSION: Intravitreal bevacizumab and subtenon triamcinolone
      injection reduces the VEGF, MCP-1 and PDGF-AA levels and increases the IL-8 level
      in the plural cytokine profiles of patients with DME, which might explain the
      limited therapeutic effect of combination therapy.

PMID- 29030693
TI  - Funaria hygrometrica Hedw. elevated tolerance to D2O: its use for the production
      of highly deuterated metabolites.
AB  - MAIN CONCLUSION: The method introduced here to grow F. hygrometrica in high
      concentrations of D 2 O is an excellent alternative to produce highly deuterated
      metabolites with broad applications in metabolic studies. Our mass spectrometry
      experiments strongly indicate the successful incorporation of deuterium into
      organic compounds. Deuterated metabolites are useful tracers for metabolic
      studies, yet their wide utilization in research is limited by the multi-step
      total synthesis required to produce them in the laboratory. Alternatively,
      deuterated metabolites can be obtained from organisms grown in D2O or deuterated
      nutrients. This approach also has limitations as D2O in high concentrations
      negatively affects the survival of most organisms. Here we report the moss
      Funaria hygrometrica as an unusual high tolerant to D2O in liquid culture. We
      found that this moss is able to grow in up to 90% D2O, a condition lethal for
      many eukaryotes. Mass spectrometric analyses of F. hygrometrica extracts showed a
      strong deuteration pattern. The ability to tolerate high concentrations of D2O
      together with the development of a rich molecular toolbox makes F. hygrometrica
      an ideal system for the production of valuable deuterated metabolites.

PMID- 29030694
TI  - Peer status in relation to psychotic experiences and psychosocial problems in
      adolescents: a longitudinal school-based study.
AB  - Social exclusion is related to many adverse mental health outcomes and may be
      particularly harmful for mental health in adolescence when peer relations become
      very important. This study examined associations between low peer status and
      psychotic experiences, psychosocial problems and short-term courses of these
      symptoms. A school-based sample of adolescents (N = 1171) was investigated in 2
      consecutive years using the 16-item Prodromal Questionnaire and the self-report
      and teacher-report version of the Strengths and Difficulties Questionnaire (SDQ).
      Peer status was measured in the second year with positive and negative peer
      nominations of classmates. Low peer status was, after adjusting for gender,
      ethnic minority status and level of education, associated with more psychosocial
      difficulties with a persistent course and a higher level of psychotic
      experiences. Of all peer status groups, being neglected had the strongest
      associations with mental health problems. The results of this study show that
      social exclusion in adolescence is related to psychotic experiences and
      psychosocial problems, emphasizing the importance of belonging to a social group.
      Customized prevention programs at individual, family and school level should
      target causes and consequences of social exclusion.

PMID- 29030695
TI  - Erratum to: Greater occipital nerve infiltration under MR guidance: Feasibility
      study and preliminary results.
AB  - The original version of this article, published on 12 July 2017, unfortunately
      contained mistakes. The following corrections have therefore been made in the
      original.

PMID- 29030696
TI  - Superposed epoch analysis of physiological fluctuations: possible space weather
      connections.
AB  - There is a strong connection between space weather and fluctuations in
      technological systems. Some studies also suggest a statistical connection between
      space weather and subsequent fluctuations in the physiology of living creatures.
      This connection, however, has remained controversial and difficult to
      demonstrate. Here we present support for a response of human physiology to
      forcing from the explosive onset of the largest of space weather events-space
      storms. We consider a case study with over 16 years of high temporal resolution
      measurements of human blood pressure (systolic, diastolic) and heart rate
      variability to search for associations with space weather. We find no
      statistically significant change in human blood pressure but a statistically
      significant drop in heart rate during the main phase of space storms. Our
      empirical findings shed light on how human physiology may respond to exogenous
      space weather forcing.

PMID- 29030697
TI  - Geomagnetic storm under laboratory conditions: randomized experiment.
AB  - The influence of the previously recorded geomagnetic storm (GS) on human
      cardiovascular system and microcirculation has been studied under laboratory
      conditions. Healthy volunteers in lying position were exposed under two
      artificially created conditions: quiet (Q) and storm (S). The Q regime playbacks
      a noise-free magnetic field (MF) which is closed to the natural geomagnetic
      conditions on Moscow's latitude. The S regime playbacks the initially recorded 6
      h geomagnetic storm which is repeated four times sequentially. The cardiovascular
      response to the GS impact was assessed by measuring capillary blood velocity
      (CBV) and blood pressure (BP) and by the analysis of the 24-h ECG recording. A
      storm-to-quiet ratio for the cardio intervals (CI) and the heart rate variability
      (HRV) was introduced in order to reveal the average over group significant
      differences of HRV. An individual sensitivity to the GS was estimated using the
      autocorrelation function analysis of the high-frequency (HF) part of the CI
      spectrum. The autocorrelation analysis allowed for detection a group of subjects
      of study which autocorrelation functions (ACF) react differently in the Q and S
      regimes of exposure.

PMID- 29030698
TI  - Biliary atresia and liver transplantation: results and thoughts for primary liver
      transplantation in select patients.
AB  - Biliary atresia (BA) is one of the most common indications for liver
      transplantation in children. Despite advances in biliary atresia surgical
      techniques, most children will ultimately require liver transplantation. Possible
      pre-operative predictors of outcome after the Kasai operation are: 1. Age at
      operation 2. Presence of the biliary atresia splenic malformation syndrome (BASM)
      3. Center specific factors 4. Liver histology and 5. Anatomic pattern of bile
      ducts found at surgery.Age at surgery is considered a strong predictor of success
      after portoenterostomy. In a recent study, age of 75 days or more at surgery was
      associated with less frequent resolution of jaundice and decreased transplant
      free survival. Similarly, the Ohi type II or III anatomy was associated with a
      higher risk of transplantation or death than type I. Inflammatory findings on pre
      operative biopsy predicted a pooreroutcome after a Kasai procedure than
      obstructive changes. Nodularity of the liver at surgery as well as ascites was
      associated with a poorer prognosis.Primary transplantation is rarely done despite
      excellent outcome. Deaths on the waiting list also have improved with routine use
      of split and live donor transplantation. The Kasai operation has the highest
      failure rate in its stated objective than any other operation in pediatric
      surgery. Failure to achieve any improvement in jaundice occurs in over 30% of all
      cases, even in the best of hands, and transplantation or listing for
      transplantation occurs in over half the children with type II and III BA by one
      year of age in countries where liver transplantation is readily available.There
      are almost no studies in children with BA that compare the outcome after liver
      transplantation for BA with or without a prior Kasai procedure. It is postulated
      that a prospective trial in children predicted to have a poor prognosis after the
      Kasai procedure based on anatomic pattern, liver histology and presence of BASM,
      would yield improved care, spare some infants needless surgery, and quite
      possibly result in diminished morbidity and mortality following liver transplant.

PMID- 29030699
TI  - Prematurity and biliary atresia: a 30-year observational study.
AB  - AIM OF STUDY: The diagnosis of biliary atresia (BA) remains challenging and delay
      can lead to significant morbidity with time to surgery a key factor in
      determining outcome. Prematurity may impact on outcome potentially delaying
      diagnosis. We sought to assess whether the premature BA infants (PBA) have a
      delayed time to surgery and as such, worse outcomes? METHODS: Review of a single
      centre prospectively maintained database. Prematurity was defined as delivery <
      37/40 gestation. PBA was compared with date-matched term biliary atresia controls
      on a 2:1 basis. Primary outcomes were clearance of jaundice (< 20 MUmol/L) and
      native liver survival. A retrospective assessment of liver fibrosis was made on
      biopsies at diagnosis and at Kasai portoenterostomy (KPE) in both premature and
      term cohorts. Data are quoted as median (range) unless indicated. A P value of <=
      0.05 was considered statistically significant. RESULTS: 21 (female n = 14, 67%)
      premature infants with BA were treated in the period Jan. 1988-Dec. 2016 and
      compared with 41 contemporaneous term BA controls. Median gestation was 33 (29
      36) weeks and birth weight 1930 (948-4230)g. Twin pregnancy (n = 10) was the
      leading cause for prematurity and significantly higher than the controls (48 vs.
      0%; P < 0.0001). Maternal co-morbidity was high (n = 10, 48%) including pre
      eclampsia (19%) and diabetes (14%). Liver biopsy was performed in 19 (90%)
      patients (all diagnostic) at a median of 57 (4-266) days. Delayed diagnosis (> 50
      days) was seen in n = 13 but not associated with parenteral nutrition use (46 vs.
      33%, P = 0.59) or phototherapy (50 vs. 83%, P = 0.19). Both BASM (33 vs. 7.5%; P
      = 0.01) and duodenal atresia (19 vs. 0%; P = 0.01) were seen more frequently in
      the PBA cohort. Mean fibrosis scores (Ishak) from diagnostic biopsies were lower
      in the premature group than the control group (2.71 vs. 3.53, P = 0.043)
      indicating less fibrosis but this equalized by time of subsequent KPE (P = 0.17).
      Primary surgery was Kasai portoenterostomy (n = 20) at an older median age than
      controls (65 vs. 56 days; P = 0.06). Liver transplantation was the primary
      procedure in one late-presenting child. There was an increased but non
      significant clearance of jaundice in the PBA group [n = 12/20 (60%) vs 20/41
      (48%); P = 0.23] post-KPE. Native liver survival and true survival were not
      different (P = 0.58 and 0.23). CONCLUSIONS: PBA infants have similar outcomes to
      term infants, despite delayed diagnosis and higher frequency of the syndromic
      form. The high incidence of discordant twins supports the theory that epigenetic
      modifications could contribute to the pathogenesis of BA. LEVEL OF EVIDENCE: IIIc
      Retrospective Matched Cohort Study.

PMID- 29030700
TI  - Pyloric stenosis: an enigma more than a century after the first successful
      treatment.
AB  - Despite hypertrophic pyloric stenosis (HPS) being one of the most frequently
      treated pediatric surgical conditions, its etiology remains incompletely
      understood. We review the diagnosis and treatment of this condition with an
      emphasis on the evolution of surgical techniques that led to laparoscopic
      pyloromyotomy, the most frequently performed technique for HPS today. In
      addition, we review key developments in the understanding of HPS etiology and
      treatment, including the postulated etiology of work-induced hypertrophy of the
      pylorus, its association with prokinetic macrolide antibiotics, and the emerging
      role of atropine sulfate as a medical treatment for HPS or a rescue treatment for
      incomplete myotomy.

PMID- 29030701
TI  - Letter to the Editor concerning ''Radiographic evaluation of indirect
      decompression of mini-open anterior retroperitoneal lumbar interbody fusion:
      oblique lateral interbody fusion for degenerated lumbar spondylolisthesis'' by
      Jun Sato et al. Eur Spine J (2017) 26: 671-678.

PMID- 29030702
TI  - The prevalence of lumbar spondylolysis in young children: a retrospective
      analysis using CT.
AB  - PURPOSE: Although lumbar spondylolysis is encountered in general population with
      an incidence estimated to be 3-10%, limited information is available for
      children. The aim of the study is to determine the prevalence of spondylolysis
      according to associated vertebral bony malformation and spinopelvic parameters in
      children under eight requiring CT evaluation for unrelated lumbar conditions.
      METHODS: Seven hundred and seventeen abdominal and pelvic multi-detector CT scans
      were obtained in patients under 8 years of age were reviewed. Two board
      certificated radiologists and two resident radiologists retrospectively evaluated
      CT scans for lumbar spondylolysis and associated malformations. Pelvic incidence
      and spondylolisthesis were reported. RESULTS: Our analysis included 717 CT scans
      in 532 children (259 girls and 273 boys). Twenty-five cases of spondylolysis were
      diagnosed (16 bilateral and 9 unilateral, 64 and 36%, respectively) in 14 boys
      (56%) and 11 girls (44%), associating with 12 grade I spondylolisthesis. The mean
      normal pelvic incidence was 45 degrees  (median 44 degrees , SD 7 degrees ). The
      prevalence of spondylolysis was 1% in children under age 3 (n = 3 among 292
      patients), 3.7% in children under age 6 (n = 17 among 454 patients) and 4.7%
      among the 532 patients. Unilateral spondylolysis was significantly associated
      with a spinal malformation (p = 0.04, Fisher's exact test), with normal pelvic
      incidence. Half of the patients with bilateral spondylolysis had high pelvic
      incidence. CONCLUSIONS: We observed a prevalence peak of unilateral spondylolysis
      in the context of a specific malformation in young infants under age 4 with
      normal pelvic incidence, and, then, a progressive increase in the prevalence of
      bilateral isolated spondylolysis.

PMID- 29030703
TI  - Osteoporotic vertebral fractures: predictive factors for conservative treatment
      failure. A systematic review.
AB  - PURPOSE: To analyze clinical, radiographic and magnetic resonance findings that
      might predict risk of complications and conservative treatment failure of
      osteoporotic vertebral fractures. METHODS: The authors conducted a systematic
      review of observational studies, collecting data on osteoporotic vertebral
      fracture and complications like vertebral collapse, kyphosis, pseudoarthrosis,
      and neurologic deficit. MeSH items such as 'spinal fracture/radiology,' 'spinal
      fracture/complications,' 'spinal fracture/diagnosis' were used. PRISMA statement
      criteria were applied, and the risk of bias was classified as low, medium, high,
      following the Newcastle-Ottawa Quality Assessment Scale (NOS). RESULTS: Eleven
      cohort studies, either retrospective or prospective, met the eligibility criteria
      and were included in the review. Major risk factors that were statistically
      predictive of the following complications were as follows; (1) vertebral
      collapse: presence of intravertebral cleft, MR T1-WI 'total type fractures' and
      T2-WI 'hypointense-wide-type'. (2) Pseudoarthrosis (nonunion): middle-column
      damage, thoracolumbar vertebrae involvement, MR T2-WI confined high-intensity
      pattern and diffuse low intensity pattern. (3) Kyphotic deformity: thoracolumbar
      fracture and superior endplate fracture. (4) Neurologic impairment: a retropulsed
      bony fragment occupying more than 42% of the sagittal diameter of the spinal
      canal and a change of more than 15 degrees  in vertebral wedge angle on lateral
      dynamic radiography. CONCLUSIONS: Shape and level of the fracture were risk
      factors associated with the progression of collapse, pseudoarthrosis, kyphotic
      deformity and neurologic impairment. MRI findings were often related to the
      failure of conservative treatment. If prognosis can be predicted at the early
      fracture stage, more aggressive treatment options, rather than conservative ones,
      might be considered.

PMID- 29030704
TI  - Expert's comment concerning Grand Rounds case entitled "Treatment of cervical
      subaxial injury in the very young child" by Z. Ozbek et al. (Eur Spine J; 2017.
      doi:10.1007/s00586-017-5316-z).

PMID- 29030705
TI  - Reviewer's comment concerning "Influence of a variation in the position of the
      arms on the sagittal connection of the gravity line with the spinal structures"
      (by J. Legaye and G. Duval-Beaupere, Eur Spine J; 2017: doi:10.1007/s00586-017
      4961-6).

PMID- 29030707
TI  - Characterization and genome comparison of an Indian isolate of bidensovirus
      infecting the silkworm Bombyx mori.
AB  - The bipartite genome of an Indian isolate of Bombyx mori bidensovirus (BmBDV),
      one of the causative agents of the fatal silkworm disease 'Flacherie', was cloned
      and completely sequenced. Nucleotide sequence analysis of this Indian isolate of
      BmBDV revealed two viral DNA segments, VD1 and VD2 as well as a DNA polymerase
      motif which supports its taxonomical status as the type species of a new family
      of Bidnaviridae. The Indian isolate of BmBDV was found to have a total of six
      putative ORFs four of which were located on the VD1 with the other two being on
      the VD2 DNA segment. The VD1 DNA segment was found to code for three non
      structural proteins including a viral DNA polymerase as well as one structural
      protein, while the VD2 DNA segment was found to code for one structural and one
      non-structural protein, similar to that of the Japanese and Zhenjiang isolates of
      BmBDV. A BmBDV ORF expression study was done through real time qPCR wherein the
      VD2 ORF 1 and 2 showed the maximum transcript levels. This is the first report of
      the genome characterization of an Indian isolate of BmBDV, infecting silkworm B.
      mori.

PMID- 29030706
TI  - Rare ADAR and RNASEH2B variants and a type I interferon signature in glioma and
      prostate carcinoma risk and tumorigenesis.
AB  - In search of novel germline alterations predisposing to tumors, in particular to
      gliomas, we studied a family with two brothers affected by anaplastic gliomas,
      and their father and paternal great-uncle diagnosed with prostate carcinoma. In
      this family, whole-exome sequencing yielded rare, simultaneously heterozygous
      variants in the Aicardi-Goutieres syndrome (AGS) genes ADAR and RNASEH2B co
      segregating with the tumor phenotype. AGS is a genetically induced inflammatory
      disease particularly of the brain, which has not been associated with a
      consistently increased cancer risk to date. By targeted sequencing, we identified
      novel ADAR and RNASEH2B variants, and a 3- to 17-fold frequency increase of the
      AGS mutations ADAR,c.577C>G;p.(P193A) and RNASEH2B,c.529G>A;p.(A177T) in the
      germline of familial glioma patients as well as in test and validation cohorts of
      glioblastomas and prostate carcinomas versus ethnicity-matched controls, whereby
      rare RNASEH2B variants were significantly more frequent in familial glioma
      patients. Tumors with ADAR or RNASEH2B variants recapitulated features of AGS,
      such as calcification and increased type I interferon expression. Patients
      carrying ADAR or RNASEH2B variants showed upregulation of interferon-stimulated
      gene (ISG) transcripts in peripheral blood as seen in AGS. An increased ISG
      expression was also induced by ADAR and RNASEH2B variants in tumor cells and was
      blocked by the JAK inhibitor Ruxolitinib. Our data implicate rare variants in the
      AGS genes ADAR and RNASEH2B and a type I interferon signature in glioma and
      prostate carcinoma risk and tumorigenesis, consistent with a genetic basis
      underlying inflammation-driven malignant transformation in glioma and prostate
      carcinoma development.

PMID- 29030708
TI  - Lethal infection of embryonated chicken eggs by Hazara virus, a model for Crimean
      Congo hemorrhagic fever virus.
AB  - Hazara virus (HAZV) is a member of the genus Orthonairovirus of the family
      Nairoviridae. HAZV is closely related to Crimean-Congo hemorrhagic fever virus
      but differs in that it is non-pathogenic to humans. To establish an infection
      model system, we tested whether embryonated chicken eggs, which are classically
      used for evaluating viral pathogenicity, are susceptible to HAZV infection. We
      demonstrated that HAZV replicates well in embryonated chicken eggs and kills 100%
      of the embryos. This can be a valuable tool to evaluate the lethality of
      nairoviruses in a biosafety level 2 laboratory.

PMID- 29030709
TI  - Bleeding risk of submuscular ICD implantation with continued oral anticoagulation
      versus heparin bridging therapy.
AB  - Recent studies have shown that subcutaneous or subfascial pacemaker- and ICD
      implantation with continued oral anticoagulation therapy is associated with lower
      risk for bleeding complications, when compared to heparin bridging strategies.
      However, ICD generators are often implanted submuscularly. We therefore compared
      the bleeding risk with continued phenprocoumon therapy vs. heparin bridging in
      patients receiving submuscular ICD implantation. Between 01/2013 and 12/2013, 104
      patients with need for oral anticoagulation received submuscular ICD or CRT-D
      implantation in our institution. 46 patients were implanted under continued
      phenprocoumon therapy while 58 patients received heparin bridging for
      implantation procedure. All ICD generators were placed submuscularly. The primary
      outcome of the study was clinically significant bleeding or device pocket
      hematoma with need for surgical revision. Mean patients age was 63.7 years, 72.1%
      were male. In patients with heparin bridging therapy, preoperative INR prior to
      ICD implantation was 1.2 +/- 0.31 while in the group of patients on continued
      phenprocoumon therapy, mean pre-OP INR was 2.4 +/- 0.47. In heparin bridging
      group, 8 (13.8%) patients experienced a clinically relevant pocket hematoma,
      while only 1 (2.2%) patient on continued phenprocoumon therapy needed surgical
      revision for pocket hematoma (P = 0.04). No further bleeding complications or
      clinically relevant pericardial effusion was observed in any of the groups and no
      perioperative thromboembolic event occurred. Submuscular ICD implantation under
      continued phenprocoumon therapy was safe and feasible. Compared to patients with
      heparin bridging therapy, those with continued phenprocoumon therapy had a lower
      incidence of clinically relevant bleeding complications.

PMID- 29030710
TI  - Comparison of functional outcome of bipolar hip arthroplasty and total hip
      replacement in displaced femoral neck fractures in elderly in a developing
      country: a 2-year prospective study.
AB  - PURPOSE: To compare the short-term functional outcome between bipolar hip
      arthroplasty (BHA) and total hip replacement (THR) in displaced femoral neck
      fractures in elderly patients in a developing country. MATERIALS AND METHODS: A
      prospective study was conducted which included a total of 42 patients of age more
      than 60 years with closed displaced femoral neck fractures, and the patients were
      randomized into two groups of 21 patients each and their outcomes were compared.
      RESULTS: At 24-month follow-up, patients in BHA group had a mean modified Harris
      hip score of 83.85 +/- 6.62 and patients in THR group had a mean modified Harris
      hip score of 88.00 +/- 5.76 (p value = 0.067). Seven (35%) patients in BHA group
      and 11 (55%) patients in THR group had hip scores from 91 to 100 (excellent), 9
      (45%) patients in BHA and seven patients (35%) in THR had hip scores 81-90 (fair)
      and 4 (20%) patients in BHA group and 2 (10%) patients in THR group were rated 71
      80 (good) and none was found in poor category. Total amount of blood  loss while
      performing BHA was 238.15 +/- 20.43 ml compared to 336.85 +/- 23.56 ml in THR (p
      < 0.0001). Mean of total duration of surgery was found to be 51.80 +/- 8.70 min
      in BHA group which was significantly lesser than 119.10 +/- 16.75 min of THR
      group (p < 0.0001). CONCLUSION: BHA being comparable to THR in terms of
      functional outcome by modified Harris hip scoring with significantly less blood
      loss during surgery, less duration of surgery, more cost-effective can be
      recommended as first line of surgical management in elderly patients with
      displaced femur neck fractures in developing countries. LEVEL OF EVIDENCE: Level
      II, lesser-quality randomized controlled trial.

PMID- 29030711
TI  - The learning curve in short-stem THA: influence of the surgeon's experience on
      intraoperative adjustments due to intraoperative radiography.
AB  - INTRODUCTION: Short-stem THA has become increasingly popular over the last
      decade. However, implantation technique differs from conventional THA and thus
      possibly involves a distinct learning curve. The purpose of this study was to
      evaluate the value of intraoperative radiography and the influence of the
      surgeon's experience on intraoperative adjustments in short-stem THA. METHODS: A
      total of 287 consecutive short-stem THAs, operated by a total of 24 senior
      consultants, consultants and residents in training, were prospectively included.
      Intraoperative radiography was performed after trial reduction. Preoperative
      planning and intraoperative outcome with regard to positioning, sizing of
      components as well as resulting offset and leg length were compared. Frequency,
      reason and type of intraoperative adjustments were documented in relation to the
      surgeon's experience. Operation time was assessed. RESULTS: One hundred and fifty
      six (54.4%) procedures were carried out by one of three senior consultants, and a
      total of nine consultants and 12 residents in training performed 105 (36.6%) and
      26 (9.0%) operations, respectively. In 121 cases (42.2%), intraoperative
      adjustments were made following intraoperative radiography. Intraoperative
      adjustments of one or more components were made by senior consultants in 51 cases
      (32.7%), by consultants in 53 cases (50.5%) and by residents in 17 cases (65.4%),
      respectively. The most common cause was undersizing of the stem. Operation time
      varied markedly between groups of surgeons. DISCUSSION: Short-stem THA involves a
      learning curve. Intraoperative radiography is decisive for prevention of
      malpositioning and undersizing of components, as well as loss of offset and leg
      length discrepancies. Hence, it should be considered mandatory, especially for
      less experienced surgeons.

PMID- 29030712
TI  - Calculating the Consequences of Left-Shifted Nav Channel Activity in Sick
      Excitable Cells.
AB  - Two features common to diverse sick excitable cells are "leaky" Nav channels and
      bleb damage-damaged membranes. The bleb damage, we have argued, causes a channel
      kinetics based "leakiness." Recombinant (node of Ranvier type) Nav1.6 channels
      voltage-clamped in mechanically-blebbed cell-attached patches undergo a damage
      intensity dependent kinetic change. Specifically, they experience a coupled
      hyperpolarizing (left) shift of the activation and inactivation processes. The
      biophysical observations on Nav1.6 currents formed the basis of Nav-Coupled Left
      Shift (Nav-CLS) theory. Node of Ranvier excitability can be modeled with Nav-CLS
      imposed at varying LS intensities and with varying fractions of total nodal
      membrane affected. Mild damage from which sick excitable cells might recover is
      of most interest pathologically. Accordingly, Na+/K+ ATPase (pump) activity was
      included in the modeling. As we described more fully in our other recent reviews,
      Nav-CLS in nodes with pumps proves sufficient to predict many of the pathological
      excitability phenomena reported for sick excitable cells. This review explains
      how the model came about and outlines how we have used it. Briefly, we direct the
      reader to studies in which Nav-CLS is being implemented in larger scale models of
      damaged excitable tissue. For those who might find it useful for teaching or
      research purposes, we coded the Nav-CLS/node of Ranvier model (with pumps) in
      NEURON. We include, here, the resulting "Regimes" plot of classes of excitability
      dysfunction.

PMID- 29030713
TI  - Nationwide survey for acute liver failure and late-onset hepatic failure in
      Japan.
AB  - BACKGROUND: A nationwide survey was performed to clarify the recent status of
      acute liver failure (ALF) and late-onset hepatic failure (LOHF) in Japan.
      METHODS: Two-step surveys for patients with ALF and LOHF meeting the Japanese
      diagnostic criteria were performed annually in 782 hospitals. The clinical
      features of the patients were then compared to those reported in previous
      surveys. RESULTS: In total, 1554 and 49 patients with ALF and LOHF, respectively,
      who were seen between 2010 and 2015 were enrolled. The subjects were classified
      into 1280 patients with hepatitis (642 non-comatose and 638 comatose) and 323
      patients without hepatitis (190 non-comatose and 133 comatose). Compared with
      patients seen between 1998 and 2009, an older patient age and a higher percentage
      of underlying extrahepatic disease were observed. Although hepatitis virus
      infection was the most frequent etiology, the percentage of patients with this
      etiology had decreased, compared with previous cohorts, while the percentages of
      patients with drug-induced liver injuries, autoimmune hepatitis, and an
      indeterminate etiology had increased. Liver transplantation was performed in 170
      patients (10.6%), whereas artificial liver support with plasmapheresis and/or
      hemodiafiltration were performed for most of the comatose patients. The outcomes
      of comatose patients were unfavorable, similar to previous surveys, especially
      the outcomes of hepatitis B virus carriers, including those with de novo
      hepatitis B (survival rate of 5.4% without liver transplantation). CONCLUSION:
      Although the clinical features, including the etiologies, of patients with ALF
      and LOHF have changed, the outcomes of patients have not improved in recent
      years.

PMID- 29030714
TI  - Cyclic fatigue resistance of XP-endo Shaper compared with different nickel
      titanium alloy instruments.
AB  - OBJECTIVE: The aims of this study were to assess and compare the resistance to
      cyclic fatigue of XP-endo Shaper (XPS; FKG Dentaire, La Chaux-de-Fonds,
      Switzerland) instruments with TRUShape (TRS; Dentsply Tulsa Dental Specialties,
      Tulsa, OK, USA), HyFlex CM (HCM; Coltene, Cuyahoga Falls, OH, USA), Vortex Blue
      (VB; Dentsply Tulsa Dental Specialties), and iRace (iR; FKG Dentaire) nickel
      titanium rotary instruments at body temperature. MATERIALS AND METHODS: Size 30,
      0.01 taper of XPS, size 30, 0.04 taper of HCM, VB, iR, and size 30, 0.06 taper of
      TRS instruments were immersed in saline at 37 +/- 1  degrees C during cyclic
      fatigue testing. The instruments were tested with 60 degrees  angle of curvature
      and a 3-mm radius of curvature. The number of cycles to failure (NCF) was
      calculated and the length of the fractured segment was measured. Fractographic
      examination of the fractured surface was performed using a scanning electron
      microscope. The data were analyzed statistically using Kruskal-Wallis H test and
      Mann-Whitney U tests. Statistical significance was set at P < 0.05. RESULTS: XPS
      had a significantly greater NCF compared with the other instruments (P < 0.001).
      The topographic appearance of the fracture surfaces of tested instruments
      revealed ductile fracture of cyclic fatigue failure. CONCLUSION: XPS instruments
      exhibited greater cyclic fatigue resistance compared with the other tested
      instruments. CLINICAL RELEVANCE: XP-endo Shaper instruments could be used more
      safely in curved canals due to their higher fatigue resistance.

PMID- 29030715
TI  - Point-of-care transcranial Doppler by intensivists.
AB  - In the unconscious patient, there is a diagnostic void between the neurologic
      physical exam, and more invasive, costly and potentially harmful investigations.
      Transcranial color-coded sonography and two-dimensional transcranial Doppler
      imaging of the brain have the potential to be a middle ground to bridge this gap
      for certain diagnoses. With the increasing availability of point-of-care
      ultrasound devices, coupled with the need for rapid diagnosis of deteriorating
      neurologic patients, intensivists may be trained to perform point-of-care
      transcranial Doppler at the bedside. The feasibility and value of this technique
      in the intensive care unit to help rule-in specific intra-cranial pathologies
      will form the focus of this article. The proposed scope for point-of-care
      transcranial Doppler for the intensivist will be put forth and illustrated using
      four representative cases: presence of midline shift, vasospasm, raised intra
      cranial pressure, and progression of cerebral circulatory arrest. We will review
      the technical details, including methods of image acquisition and interpretation.
      Common pitfalls and limitations of point-of-care transcranial Doppler will also
      be reviewed, as they must be understood for accurate diagnoses during
      interpretation, as well as the drawbacks and inadequacies of the modality in
      general.

PMID- 29030716
TI  - Prevalence, transmission, and host specificity of Cryptosporidium spp. in various
      animal groups from two French zoos.
AB  - Cryptosporidium represents a major cause of gastrointestinal illness in humans
      and animals including domestic, wild, and in captivity animals, and more than 30
      validated species of Cryptosporidium are recognized as infectious to different
      hosts such as mammals, birds, reptiles, amphibians, and fish. Therefore, numerous
      investigations have been conducted worldwide in order to shed light on the
      epidemiology of this parasite and to explore its potential reservoirs. Few
      surveys, targeting humans and animals have been carried out regarding the
      epidemiology of Cryptosporidium spp. in France and no data are available about
      the circulation of this parasite in French zoological gardens. Herein, we
      determined the prevalence of Cryptosporidium in animals housed in two French
      zoos. A total of 307 fecal samples belonging to 161 species were screened by
      nested PCR. Overall, Cryptosporidium DNA was detected in 1.9% of the 161 species
      and 1% of the total number of fecal samples tested. Additionally, three
      Cryptosporidium species were identified: C. galli, C. andersoni, and C. tyzzeri.
      To our knowledge, this is the first molecular study focused on Cryptosporidium
      infection in captivity animals in France. This study is of interest considering
      the exposure of a large number of humans and animals to this waterborne
      protozoan, found ubiquitously in the environment.

PMID- 29030717
TI  - Baseline Cigarette Smoking Status as a Predictor of Virologic Suppression and CD4
      Cell Count During One-Year Follow-Up in Substance Users with Uncontrolled HIV
      Infection.
AB  - Cigarette smoking is prevalent in people living with HIV/AIDS (PLHIV) who abuse
      alcohol and/or illicit substances. This study evaluated whether smoking is
      predictive of virologic non-suppression (> 200 copies/mL) and low CD4 count (<
      200 cells/mm3) during 1-year follow-up in medically hospitalized, substance-using
      PLHIV recruited for a multi-site trial. Smoking status was assessed with the
      Heaviness of Smoking Index (HSI). Analyses revealed that, controlling for
      baseline differences and adherence to antiretroviral therapy, non-smokers (n =
      237), compared to smokers scoring in the medium-to-high range on the HSI (n =
      386), were significantly more likely to achieve viral suppression (OR 1.50, 95%
      CI 1.02, 2.20). There was a significant smoking-by-time interaction for CD4 cell
      count (chi2(1) = 4.08, p < .05), with smokers less likely to have low CD4 count
      at baseline and 6-month follow-up, but more likely to have low CD4 count at 12
      month follow-up. The results suggest that smoking may play a role in
      immunological functioning in HIV-infected substance users. ClinicalTrials.gov
      Identifier: NCT01612169.

PMID- 29030718
TI  - Lacosamide in patients with gliomas and uncontrolled seizures: results from an
      observational study.
AB  - To report the efficacy and tolerability of lacosamide as an add-on treatment in
      patients with gliomas and uncontrolled seizures despite conventional
      antiepileptic drugs (AEDs). We conducted an observational study on 71 patients to
      describe patterns of response to lacosamide and the association between clinico
      pathological factors and seizure control. We observed at 3, 6 and 9 months a
      seizure reduction >= 50% in 74.6, 76 and 86.2% of patients and a seizure freedom
      in 42.2, 43 and 50%, respectively. The median number of seizures in the 3 months
      before treatment was 13, and decreased to 3 between baseline and 6 months, and to
      0.5 between 6 and 9 months. The best seizure response was observed at 3 months
      (62%). Sixty per cent of patients displayed the maximum seizure control with
      doses of lacosamide of 100-250 mg/day, while 21% needed doses up to 400 mg/day.
      Seizure reduction >= 50% and seizure freedom were higher in patients who received
      lacosamide as first add-on compared to those who received a later adjunctive
      therapy. A reduction >= 50% of seizures was observed in a proportion of patients
      with progressive disease on MRI. Age > 45 years (OR 0.11, 95% CI 0.02-0.63, p =
      0.013) was a significant predictor of seizure freedom at 9 months on multivariate
      analysis. The study suggests that lacosamide, when added to any baseline AEDs, is
      effective in obtaining a high seizure reduction and seizure freedom regardless of
      the tumor activity and response to antineoplastic therapies.

PMID- 29030719
TI  - Guidelines for the management of thoracic aortic disease in 2017.
AB  - This review provides a general overview of the consensus statement from the 2010
      more recent updates AHA/ACC Guidelines for the Diagnosis and Management of
      Patients with Thoracic Aortic Disease, and highlights current practice patterns.
      The suggestions herein are intended to facilitate clinical decision making in the
      management of thoracic aortic disease. The main intent of this report is to
      highlight screening, surveillance, initial and definitive management of thoracic
      aortic disease, and special populations that should be considered.

PMID- 29030720
TI  - Molecular Diagnostic Testing in Cardiac Transplantation.
AB  - PURPOSE OF REVIEW: Acute rejection is one of the most feared complications of
      cardiac transplantation. Developing non-invasive methods for detection and
      surveillance of acute rejection have long been a goal for post-transplant care.
      RECENT FINDINGS: Here, we will review molecular diagnostic tests that are
      currently in use or under development to diagnose acute cellular rejection after
      cardiac transplantation. Gene expression, microRNA, molecular microscope, and
      cell-free DNA assays offer non-invasive alternatives to the endomyocardial biopsy
      for acute rejection surveillance.

PMID- 29030721
TI  - Percutaneous treatment of hepatic cystic echinococcosis: the success of alcohol
      as a single endocavitary agent in PAIR, catheterization, and modified
      catheterization techniques.
AB  - OBJECTIVES: This retrospective study aims at demonstrating the success rate,
      effectiveness, and advantages of alcohol as a scolicidal and sclerosing agent for
      the percutaneous treatment of liver hydatid cysts. METHODS: A total of 554 liver
      hydatid cysts obtained from 347 patients admitted between January 2008 and
      February 2016 were retrospectively investigated. Of these, 435 (78.5%), 91
      (16.4%), and 28 (5%) were classified as Gharbi type 1, 2, and 3, respectively.
      Type 1 and 2 cysts were treated using PAIR (puncture, aspiration, injection,
      respiration) and single puncture catheterization methods; type 3 lesions were
      treated using a modified catheterization technique. Alcohol was used as a
      scolicidal and sclerosing agent in all procedures. RESULTS: After excluding three
      lesions (0.5%) because of lack of parenchymal support during catheterization, 274
      (49.7%), 250 (45.3%), and 27 (4.9%) of 551 lesions were treated with PAIR, single
      puncture catheterization, and modified catheterization techniques, respectively.
      Therefore, a 99.5% of technical success rate was obtained. Major complications in
      2 patients (0.5%) and minor complications were observed in 36 patients (10.3%).
      Mean hospital stay was 1.55+/-2.3 days (range: 0-23 days). Patients were followed
      up for mean 19.6 months (range: 6-83 months), during which recurrences were
      detected in 19 patients (5.4%). CONCLUSIONS: The use of alcohol as a scolicidal
      and sclerosing agent during the percutaneous treatment of liver hydatid cysts is
      associated with a high success rate and low rates of recurrence and
      complications, and should be considered an important alternative to surgical
      procedures.

PMID- 29030723
TI  - Eric Davidson and deep time.
AB  - Eric Davidson had a deep and abiding interest in the role developmental
      mechanisms played in generating evolutionary patterns documented in deep time,
      from the origin of the euechinoids to the processes responsible for the
      morphological architectures of major animal clades. Although not an evolutionary
      biologist, Davidson's interests long preceded the current excitement over
      comparative evolutionary developmental biology. Here I discuss three aspects at
      the intersection between his research and evolutionary patterns in deep time:
      First, understanding the mechanisms of body plan formation, particularly those
      associated with the early diversification of major metazoan clades. Second, a
      critique of early claims about ancestral metazoans based on the discoveries of
      highly conserved genes across bilaterian animals. Third, Davidson's own
      involvement in paleontology through a collaborative study of the fossil embryos
      from the Ediacaran Doushantuo Formation in south China.

PMID- 29030722
TI  - Predelivery uterine artery embolization for placental anomalies: some
      clarifications.

PMID- 29030724
TI  - Exploratory behavior of a native anuran species with high invasive potential.
AB  - Exploratory behavior can be a key component of survival in novel or changing
      environments, ultimately determining population establishment. While many studies
      have investigated the behavior of wild animals in response to novel food items or
      objects, our understanding of how they explore novel environments is limited.
      Here, we examine how experience affects the foraging behavior of a species with
      high invasive potential. In particular, we investigate the movement and behavior
      of cane toads as a function of experience in a novel environment, and how the
      presence of food modulates exploration. Cane toads, from a population in their
      native range, were repeatedly tested in a large, naturalistic arena with or
      without food present. Both groups exhibited significant but different changes in
      exploratory behavior. While toads in an environment without food reduced
      exploratory behavior over trials, those with food present increased both food
      intake per trial and the directness of their paths to food, resulting in fewer
      approaches to food patches over time. Our results suggest that cane toads learn
      patch location and provide preliminary evidence suggesting toads use spatial
      memory, not associative learning, to locate food. In sum, we show that with
      experience, cane toads alter their behavior to increase foraging efficiency. This
      study emphasizes the role of learning in foraging in cane toads, a characteristic
      that may have facilitated their success as invaders.

PMID- 29030725
TI  - Domestic horses (Equus caballus) prefer to approach humans displaying a
      submissive body posture rather than a dominant body posture.
AB  - Signals of dominance and submissiveness are central to conspecific communication
      in many species. For domestic animals, sensitivities to these signals in humans
      may also be beneficial. We presented domestic horses with a free choice between
      two unfamiliar humans, one adopting a submissive and the other a dominant body
      posture, with vocal and facial cues absent. Horses had previously been given food
      rewards by both human demonstrators, adopting neutral postures, to encourage
      approach behaviour. Across four counterbalanced test trials, horses showed a
      significant preference for approaching the submissive posture in both the first
      trial and across subsequent trials, and no individual subject showed an overall
      preference for dominant postures. There was no significant difference in latency
      to approach the two postures. This study provides novel evidence that domestic
      horses may spontaneously discriminate between, and attribute communicative
      significance to, human body postures of dominance; and further, that familiarity
      with the signaller is not a requirement for this response. These findings raise
      interesting questions about the plasticity of social signal perception across the
      species barrier.

PMID- 29030726
TI  - Correction to: A Scoping Review of Economic Evaluations Alongside Randomised
      Controlled Trials of Home Monitoring in Chronic Disease Management.
AB  - Table 2, 'Stoddart [19]' row: The cell entry in the 'Mean cost per control
      patient (SE)' column.

PMID- 29030727
TI  - [Parenteral nutrition in premature babies with a birth weight <1500g: a
      systematic single-center analysis and comparison with current guidelines].
AB  - BACKGROUND: Parenteral and enteral nutrition are essential for both growth and
      development of preterm infants. Based on the results of many studies, the rate of
      nutritional growth and the amount of substrate delivered parenterally are under
      debate. OBJECTIVE: The main aim of this study was to assess parenteral nutrition
      in very and extremely immature preterm infants, i.e. very low birth weight (VLBW,
      birth weight <1500g) and extremely low birth weight (ELBW, birth weight <1000g)
      neonates, and to compare the amount of parenterally delivered substrate in our
      neonatal intensive care unit (NICU) to current German guidelines. METHODS:
      Retrospective audit at our tertiary NICU at the University Children's Hospital of
      Saarland, Homburg, Germany between 1 January 2009 and 31 December 2010. RESULTS:
      In total, 100 premature neonates were included. The mean gestational age was 29.6
      weeks (range 24.4-34.1 weeks) and the mean birth weight was 1119 g +/- 260 g
      (range 570 g-1490 g). Comparing the amount of fluids, glucose, amino acids,
      lipids and kcals with the current guidelines of the German Society for
      Nutritional Medicine in preterm infants, only glucose was adequately given;
      however, a substantial number of weight-dependent (more often in ELBW neonates)
      episodes of hyperglycemia requiring insulin treatment were also seen. During the
      first 3 weeks of life a substantial drop in body weight, length and head
      circumference occurred in our study cohort. In contrast, at 2 years corrected
      age, catch-up growth was seen in our cohort with anthropometric data now
      comparable to healthy term infants. Using the Bayley II test for developmental
      outcome assessment, at 2 years corrected age 78.6% (33/42) of infants
      demonstrated normal development. CONCLUSIONS: This retrospective data analysis
      demonstrated inadequate provision of parenteral nutrition in our NICU, which was
      often not in line with current German guidelines. This was associated with
      inadequate growth in our cohort, most notably during the first 3 weeks of life;
      however, implementation of current guidelines is impeded by metabolic
      disturbances in this cohort, most notably in ELBW neonates. Whether adherence to
      published guidelines will result in better early ex utero growth, and whether
      this normalized growth pattern will translate into better long-term outcome on a
      metabolic and neurological level, remains unclear.

PMID- 29030728
TI  - Clinical trial design and recommendations: collectively, we can take them.
AB  - There is dynamic opportunity to advance medical research and clinical trial
      innovation in the USA and throughout the world. Identified problems and solutions
      in the clinical research and clinical trial enterprise have emerged over recent
      years. Strategic plans, public reports, expertise panels and international
      agreements have been produced, and now is the time to move forward collectively.
      Recommendations should be reviewed, especially because global healthcare can take
      them. A robust and future medical research enterprise hinges on maximized
      clinical trial efficiency, both in the USA and abroad.

PMID- 29030729
TI  - Long photoperiod affects the maize transition from vegetative to reproductive
      stages: a proteomic comparison between photoperiod-sensitive inbred line and its
      recurrent parent.
AB  - Maize (Zea mays L.) is a typical short-day plant that is produced as an important
      food product and industrial material. The photoperiod is one of the most
      important evolutionary mechanisms enabling the adaptation of plant developmental
      phases to changes in climate conditions. There are differences in the photoperiod
      sensitivity of maize inbred lines from tropical to temperate regions. In this
      study, to identify the maize proteins responsive to a long photoperiod (LP), the
      photoperiod-insensitive inbred line HZ4 and its near-isogenic line H496, which is
      sensitive to LP conditions, were analyzed under long-day conditions using
      isobaric tags for relative and absolute quantitation. We identified 5259 proteins
      in maize leaves exposed to the LP condition between the vegetative and
      reproductive stages. These proteins included 579 and 576 differentially
      accumulated proteins in H496 and HZ4 leaves, respectively. The differentially
      accumulated proteins (e.g., membrane, defense, and energy- and ribosome-related
      proteins) exhibited the opposite trends in HZ4 and H496 plants during the
      transition from the vegetative stage to the reproductive stage. These results
      suggest that the photoperiod-associated fragment in H496 plants considerably
      influences various proteins to respond to the photoperiod sensitivity. Overall,
      our data provide new insights into the effects of long-day treatments on the
      maize proteome, and may be useful for the development of new germplasm.

PMID- 29030730
TI  - Introduction: Eric Davidson and the molecular biology of evolution and
      development.
AB  - Between November 30th and December 2nd, 2015, the Jacques Loeb Centre for the
      History and Philosophy of the Life Sciences at Ben-Gurion University of the Negev
      in Beer Sheva (Israel) held its Eighth International Workshop under the title
      "From Genome to Gene: Causality, Synthesis and Evolution". Eric Davidson, the
      founder of the concept of developmental Gene Regulatory Networks, had regularly
      attended the previous meetings, and his participation in this one was expected,
      but he suddenly passed away 3 months before. In this paper, we provide an
      introduction and overview on five papers that were presented at the workshop and
      examine the importance of genomes and gene regulatory networks in extant biology,
      developmental biology, evolutionary biology and medicine, as well as a collection
      of remembrances of Eric Davidson, of his personality as well as of his scientific
      contributions. Historical perspectives are provided, and the ethical issues
      raised by the new tools developed to modify the genome are also discussed.

PMID- 29030731
TI  - Burden of migraine in a Kuwaiti population: a door-to-door survey.
AB  - BACKGROUND: Migraine prevalence and disability imprints on Kuwaiti population are
      underreported. We aimed to measure the prevalence of migraine and to assess its
      burden in Kuwait. METHODS: A cross-sectional community-based study was conducted
      which included biologically unrelated Kuwaiti adult population aged 18-65 years.
      They were randomly recruited from all six governments of Kuwait using stratified
      multistage cluster sampling. Trained interviewers visited the samples in door-to
      door approach. The Headache-Attributed Restriction, Disability, and Social
      Handicap and Impaired Participation (HARDSHIP) questionnaire was used to collect
      the data. Demographic enquires were followed by diagnostic and disability
      questions. RESULTS: A total of 15,523 subjects were identified; of whom 3588
      (23%) were diagnosed as episodic migraine and 845 (5.4%) as chronic headache.
      Prevalence of episodic migraine was 31.71% in female versus 14.88% in males (P <
      0.01) with a mean age of 34.56 +/- 10.17 years. Most of migraine cohort (64.4%)
      sought medical advice with respect to their migraine headaches and the majority
      (62.4%) were seen by general practitioners (GPs) while 17.2% were assessed by
      neurologists and 3.7% was seen by other specialties. Tension type headache and
      sinus-related headaches were diagnosed in 8.9% and 2.1% of migraine subjects
      respectively. The majority (94.6%) of migraine subjects used symptomatic drugs
      for headache attacks, whereas 39.9% were taking preventive medication. In the
      preceding 3 months to the survey, subjects with episodic migraine had lost a mean
      of 1.97 days from their paid work or school attendance compared to 6.62 days in
      chronic headache sufferers (P < 0.001). Additionally, subjects with episodic
      migraine lost a mean of 1.40 days from household work compared to 5.35 days in
      subjects with chronic headache (P < 0.001). Participants with episodic migraine
      and chronic headache missed a mean of 2.81 and 3.85 days on social occasions, in
      the preceding 3 months (P < 0.001). CONCLUSIONS: Migraine in Kuwait is highly
      prevalent and it has a significant impact on activity of daily living, schooling/
      employment and social occasions of patients. Accurate diagnosis, effective
      abortive and preventive treatments of migraine are paramount to improve quality
      of life and as well as cost saving.

PMID- 29030732
TI  - Deguelin induces PUMA-mediated apoptosis and promotes sensitivity of lung cancer
      cells (LCCs) to doxorubicin (Dox).
AB  - As a natural agent for chemotherapy, deguelin remarkably suppresses proliferation
      in numerous solid cancers. Nevertheless, the molecular mechanisms of its
      suppression are still insufficient. In our research, it was revealed that
      deguelin induced cell death of lung cancer cells (LCCs) by triggering expression
      of PUMA. Deguelin triggered PUMA induction independently of p53 via suppression
      of PI3K/AKT pathway, therefore stimulating Foxo3a to bind with PUMA promoter and
      stimulate its transcription. Subsequent to activation, PUMA motivated Bax as well
      as the intrinsic mitochondrial cell death pathway. Removal of PUMA from LCC cells
      led to deguelin resistance, suggesting deguelin-induced cell death was modulated
      by PUMA. Furthermore, we demonstrated that deguelin enhanced the chemotherapeutic
      sensitivity of doxorubicin in vitro and in vivo, which were associated with
      potentiated PUMA induction. Taken together, these results establish a critical
      role of PUMA in mediating the anticancer effects of deguelin in lung cancer cells
      and provide the rationale for clinical evaluation.

PMID- 29030733
TI  - High Yield Preparation of Functionally Active Catalytic-Translocation Domain
      Module of Botulinum Neurotoxin Type A That Exhibits Uniquely Different Enzyme
      Kinetics.
AB  - Botulinum neurotoxins (BoNTs) are the most toxic proteins known to cause flaccid
      muscle paralysis as a result of inhibition of neurotransmitter release from
      peripheral cholinergic synapses. BoNT type A (BoNT/A) is a 150 kDa protein
      consisting of two major subunits: light chain (LC) and heavy chain (HC). The LC
      is required for the catalytic activity of neurotoxin, whereas the C and N
      terminal domains of the HC are required for cell binding, and translocation of LC
      across the endosome membranes, respectively. To better understand the structural
      and functional aspects of BoNT/A intoxication we report here the development of
      high yield Escherichia coli expression system (2-20-fold higher yield than the
      value reported in the literature) for the production of recombinant light chain
      translocation domain (rLC-TD/A) module of BoNT/A which is catalytically active
      and translocation competent. The open reading frame of rLC-TD/A was PCR amplified
      from deactivated recombinant BoNT/A gene (a non-select agent reagent), and was
      cloned using pET45b (+) vector to express in E. coli cells. The purification
      procedure included a sequential order of affinity chromatography, trypsinization,
      and anion exchange column chromatography. We were able to purify > 95% pure,
      catalytically active and structurally well-folded protein. Comparison of enzyme
      kinetics of purified LC-TD/A to full-length toxin and recombinant light chain A
      suggest that the affinity for the substrate is in between endopeptidase domain
      and botulinum toxin. The potential application of the purified protein has been
      discussed in toxicity and translocation assays.

PMID- 29030734
TI  - Erratum to: Inhibition of Angiotensin II-Induced Cardiac Fibrosis by Atorvastatin
      in Adiponectin Knockout Mice.
AB  - In the original published article, Victor Serebruany was designated as the
      corresponding author in error. The corresponding author is Jong Sung Park. Dr.
      Park can be reached by email at thinkmed@dau.ac.kr.

PMID- 29030735
TI  - Suicide Attempts Among Adolescents with Self-Reported Disabilities.
AB  - This study examines the relative risk for suicide attempts (SA) among high-school
      students self-identifying with one or more disability classifications (nine);
      assesses the extent to which youth with disabilities are disproportionately
      vulnerable to risk factors that predict suicidal behavior among all adolescents;
      and explores whether disability status adds to risk for SA after accounting for a
      comprehensive set of known risk and protective factors for SA. Analyses using
      Wisconsin's 2012 Dane County Youth Assessment Survey data found that youth in
      each disability category were 3-9 times more likely to report suicide attempt(s)
      relative to peers, and the endorsement of multiple disabilities tripled the risk
      SA relative to youth reporting a single disability. Some disability sub-groups,
      including youth reporting autism spectrum disorder, hearing, and vision
      impairments reported surprisingly high rates of SA. While youth with disabilities
      reported disproportionate exposure to adversity in every life domain examined,
      similar to youth reporting SA, disability status added unique risk for suicidal
      behavior. This suggests that disability may be a 'fundamental cause' of suicidal
      behavior, a question that requires further investigation.

PMID- 29030736
TI  - N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) inhibits the angiogenic
      activity of heparin-binding growth factors.
AB  - The peptides N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) and BOC-Met-Leu
      Phe (BOC1) are widely used antagonists of formyl peptide receptors (FPRs), BOC2
      acting as an FPR1/FPR2 antagonist whereas BOC1 inhibits FPR1 only. Extensive
      investigations have been performed by using these FPR antagonists as a tool to
      assess the role of FPRs in physiological and pathological conditions. Based on
      previous observations from our laboratory, we assessed the possibility that BOC2
      may exert also a direct inhibitory effect on the angiogenic activity of vascular
      endothelial growth factor-A (VEGF-A). Our data demonstrate that BOC2, but not
      BOC1, inhibits the angiogenic activity of heparin-binding VEGF-A165 with no
      effect on the activity of the non-heparin-binding VEGF-A121 isoform. Endothelial
      cell-based bioassays, surface plasmon resonance analysis, and computer modeling
      indicate that BOC2 may interact with the heparin-binding domain of VEGF-A165,
      thus competing for heparin interaction and preventing the binding of VEGF-A165 to
      tyrosine kinase receptor VEGFR2, its phosphorylation and downstream signaling. In
      addition, BOC2 inhibits the interaction of a variety of heparin-binding
      angiogenic growth factors with heparin, including fibroblast growth factor 2
      (FGF2) whose angiogenic activity is blocked by the compound. Accordingly, BOC2
      suppresses the angiogenic potential of human tumor cell lines that co-express
      VEGF-A and FGF2. Thus, BOC2 appears to act as a novel multi-heparin-binding
      growth factor antagonist. These findings caution about the interpretation of FPR
      focusing experimental data obtained with this compound and set the basis for the
      design of novel BOC2-derived, FPR independent multi-target angiogenesis
      inhibitors.

PMID- 29030737
TI  - Comment on "Long-Term Survival Benefit and Potential for Cure after R1 Resection
      for Colorectal Liver Metastases": A Reply.

PMID- 29030738
TI  - Survival Analysis in a Randomized Trial of HIPEC in Ovarian Cancer.

PMID- 29030739
TI  - What Advisors Want from Advisees: A Survey Within One Academic Psychiatry
      Department.

PMID- 29030740
TI  - Much of What We Have Needed to Know as Academic Managers We Learned Leading
      Teenage Jazz Groups.

PMID- 29030741
TI  - The Role of Next-Generation Sequencing in Sarcomas: Evolution From Light
      Microscope to Molecular Microscope.
AB  - PURPOSE OF REVIEW: Sarcomas are rare, heterogeneous group of soft tissue and bone
      tumors. Precise diagnosis of specific subtypes is challenging using conventional
      methods. Herein, we review the role of next-generation sequencing (NGS)
      technology that is used for rapid sequencing of DNA and RNA. RECENT FINDINGS:
      Recent sarcoma specific studies recommend that molecular genetic testing should
      be added at diagnosis for appropriate clinical management in addition to
      diagnosis by expert pathologists. NGS has already been used to identify
      potentially actionable mutations, copy number alterations, and gene fusions.
      Rationally, choosing a drug based on an individual patient profile aka:
      "precision oncology" has been so far limited to few case reports in sarcomas. As
      we improve our ability to deliver personalized medicine using all modalities
      including conventional therapy, more patients may eventually benefit. As the cost
      and capacity of NGS outpace Moore's law, so does the probability of success.

PMID- 29030742
TI  - PTEN Gene Induces Cell Invasion and Migration via Regulating AKT/GSK-3beta/beta
      Catenin Signaling Pathway in Human Gastric Cancer.
AB  - BACKGROUND: Abnormality of PTEN gene and Wnt/beta-catenin signaling have been
      strongly implicated in various malignant cancers. Recently, it has been noted
      that a functional interaction/cross-talk was found between the PTEN/PI3K/AKT and
      Wnt/beta-catenin, which plays a key role in the development of cancers. However,
      few related studies on gastric cancer are available. AIM: We examined the
      expression of PTEN and beta-catenin in gastric cancer tissues and detected
      whether down-regulation of PTEN promotes the migration and invasion in gastric
      cancer cells along with its underlying mechanism. MATERIALS AND METHODS:
      Immunocytochemistry, a wound healing assay, a Matrigel invasion assay, an
      immunofluorescence staining were performed to detect expression of PTEN and beta
      catenin in gastric cancer and adjacent normal tissues, cell migration, cell
      invasion, and the effects of PTEN knockdown on beta-catenin in cells,
      respectively. Further, MMP-2 and MMP-9 activities were analyzed by zymography
      assay. The changes in related proteins were further quantified by western
      blotting. RESULTS: Low expression of PTEN was found in majority of gastric cancer
      tissues, which showed significant associations with differentiation grade in
      gastric cancer patients. Further, a negative correlation was revealed between
      PTEN and beta-catenin protein expression in gastric cancer tissues (r = - 0.546,
      P < 0.01). Additionally, PTEN knockdown promoted the migration and invasion of
      cells and caused an obvious increase in p-AKT, p-GSK-3beta, beta-catenin, E
      cadherin, MMP-7, MMP-2, and MMP-9 in gastric cancer cells. CONCLUSION: Our
      results indicated PTEN gene might induce cell invasion and migration via
      regulating AKT/GSK-3beta/beta-catenin signaling pathway, playing a vital role in
      the progression of gastric cancer.

PMID- 29030743
TI  - miR-182 and miR-135b Mediate the Tumorigenesis and Invasiveness of Colorectal
      Cancer Cells via Targeting ST6GALNAC2 and PI3K/AKT Pathway.
AB  - BACKGROUND: Metastasis is a leading cause of cancer-related death including
      colorectal cancer (CRC). MicroRNAs are known to regulate cancer pathways and to
      be expressed aberrantly in cancer. Aberrant sialylation is closely associated
      with malignant phenotype of tumor cells, including invasiveness and metastasis.
      AIM: This study aimed to investigate the association of miR-182 and miR-135b with
      proliferation and invasion by targeting sialyltransferase ST6GALNAC2 in CRC cells
      and explore the potential molecular mechanism. METHODS: We measured the levels of
      miR-182, miR-135b, and ST6GALNAC2 in a series of CRC cell lines and tissues using
      real-time PCR. Bioinformatics analysis and luciferase reporter assay were
      performed to test the direct binding of miR-182 and miR-135b to the target gene
      ST6GALNAC2. We also analyzed the possible role of miR-182/-135b on colony
      formation, wound healing, invasion, and tube formation. RESULTS: The expression
      of miR-182 and miR-135b was higher in tumor tissues compared to adjacent
      noncancerous tissues of CRC patients, as well as up-regulated in SW620 cells than
      in SW480 cells with different metastatic potential. By applying bioinformatics
      analysis and luciferase reporter assay, we identified ST6GALNAC2 as the direct
      target of miR-182/-135b. Furthermore, miR-182/-135b inhibited significantly
      ST6GALNAC2 expression, and consistently, ST6GALNAC2 mediated migration, adhesion,
      invasion, proliferation, and tumor angiogenesis in CRC cell lines. Additionally,
      PI3K/AKT signaling pathway was regulated by miR-182/135b, which was partially
      blocked by altered level of ST6GALNAC2 in CRC. CONCLUSIONS: The miR-182/
      135b/ST6GALNAC2/PI3K/AKT axis may serve as a predictive biomarker and a potential
      therapeutic target in CRC treatment.

PMID- 29030744
TI  - Peptide Tyrosine Tyrosine 3-36 Reduces Meal Size and Activates the Enteric
      Neurons in Male Sprague-Dawley Rats.
AB  - BACKGROUND: Peptide tyrosine tyrosine 3-36 (peptide YY 3-36 or PYY 3-36) reduces
      food intake by unknown site(s). AIM: To test the hypothesis that the
      gastrointestinal tract contains sites of action regulating meal size (MS) and
      intermeal interval (IMI) length by PYY 3-36. METHODS: Peptide YY 3-36 (0, 1, 5,
      10 and 20 nmol/kg) was injected in the aorta, the artery that supplies the
      gastrointestinal tract, prior to the onset of the dark cycle in free feeding male
      Sprague-Dawley rats and food intake was measured. Then, PYY 3-36 (25 nmol/kg) was
      injected intraperitoneally in these rats and Fos-like immunoreactivity (Fos-LI, a
      marker for neuronal activation) was quantified in the small intestinal enteric
      neurons, both myenteric and submucosal, and the dorsal vagal complex (DVC) of the
      hindbrain. RESULTS: PYY 3-36 reduced first MS, decreased IMI length, shortened
      duration of first meal and increased Fos-LI in enteric and DVC neurons. However,
      PYY 3-36 failed to change the size of the second meal, satiety ratio, latency to
      first meal, number of meals and 24 h intake relative to saline control.
      CONCLUSION: The gastrointestinal tract may contain sites of action regulating MS
      reduction by PYY 3-36.

PMID- 29030745
TI  - Modulation of Gut Microbiota by Maillard Reaction Products in Intestinal
      Inflammation: Are We What We Eat?

PMID- 29030747
TI  - 2017 CMP Honoree: Professor Shirley Lindenbaum.

PMID- 29030746
TI  - Platelet microRNA for predicting acute myocardial infarction.
AB  - Acute myocardial infarction (AMI) is one of the leading causes of morbidity and
      mortality worldwide, while early diagnosis still represents an upmost priority.
      While platelet activation is critical for AMI pathogenesis, the role of platelet
      microRNAs (pmiRNAs) as biomarkers for AMI is unclear. Furthermore, correlations
      between the levels of pmiRNAs and indices of platelet activity are also unknown.
      Expression of platelet miR-1, miR-21, miR-126, miR-150 and miR-223 were
      prospectively assessed in 20 ST-segment elevation myocardial infarction (STEMI)
      patients, and 40 healthy volunteers. Platelet reactive units (PRU) were assessed
      with cartridge analyzer, and vasodilator-stimulated phosphoprotein (VASP) was
      measured by flow cytometry. There were no significant changes in pmiR-1
      expression. Expressions of pmiR-21 and pmiR-126 were decreased, while pmiR-150
      and pmiR-223 were increased in STEMI patients when compared to controls (all p <
      0.01). However, only pmiR-126 exhibited correlation with plasma cardiac troponin
      I (r = - 0.556, p = 0.011) in STEMI. There was no correlation between pmiRNAs
      with PRU or VASP during admission, or at 48 h post-stenting. Among tested
      pmiRNAs, pmiR-126 may serve as a potential novel biomarker for STEMI, while pmiR
      1, pmiR-21, pmiR-150, and pmiR-223 were not particularly useful. Moreover, since
      assessed pmiRNA expression did not correlate well with platelet activity indices
      their potential diagnostic utility is quite limited.

PMID- 29030748
TI  - Neuroimaging of Cavernous Malformations.
AB  - PURPOSE OF REVIEW: Cerebral cavernous malformations (CCMs) are common vascular
      abnormalities often discovered on imaging as an incidental finding. The most
      common clinical presentations of CCMs include seizure, headache, focal
      neurological deficits, and intracranial hemorrhage. This article discusses the
      most recent guidelines including imaging diagnostic criteria and radiographic
      standards of CCMs and reviews the utility of currently available imaging
      techniques. RECENT FINDINGS: Gradient echo T2*-weighted imaging and
      susceptibility-weighted imaging are the recommended imaging protocols for
      evaluation of suspected CCMs. Diffusion tensor imaging-based tractography
      provides visualization of the eloquent white matter tracks in the brain. This
      imaging is increasingly used in clinical practice to assist in selecting the
      optimal surgical approach, especially for brainstem lesions. Quantitative
      susceptibility mapping and dynamic contrast-enhanced quantitative perfusion are
      presently considered experimental. Its proposed value might prove helpful in the
      future to monitor disease activity and response to treatments. The choice of
      imaging modality of CCMs depends on the goals the clinician expects to achieve,
      such as establishing the initial diagnosis, follow-up and monitoring disease
      activity, preoperative, intraoperative, and postoperative evaluation, or research
      and experimental work on patients with CCM.

PMID- 29030749
TI  - Bayesian Sensitivity Analysis of a Nonlinear Dynamic Factor Analysis Model with
      Nonparametric Prior and Possible Nonignorable Missingness.
AB  - Many psychological concepts are unobserved and usually represented as latent
      factors apprehended through multiple observed indicators. When multiple-subject
      multivariate time series data are available, dynamic factor analysis models with
      random effects offer one way of modeling patterns of within- and between-person
      variations by combining factor analysis and time series analysis at the factor
      level. Using the Dirichlet process (DP) as a nonparametric prior for individual
      specific time series parameters further allows the distributional forms of these
      parameters to deviate from commonly imposed (e.g., normal or other symmetric)
      functional forms, arising as a result of these parameters' restricted ranges.
      Given the complexity of such models, a thorough sensitivity analysis is critical
      but computationally prohibitive. We propose a Bayesian local influence method
      that allows for simultaneous sensitivity analysis of multiple modeling components
      within a single fitting of the model of choice. Five illustrations and an
      empirical example are provided to demonstrate the utility of the proposed
      approach in facilitating the detection of outlying cases and common sources of
      misspecification in dynamic factor analysis models, as well as identification of
      modeling components that are sensitive to changes in the DP prior specification.

PMID- 29030750
TI  - A New Explanation and Proof of the Paradoxical Scoring Results in
      Multidimensional Item Response Models.
AB  - In multidimensional item response models, paradoxical scoring effects can arise,
      wherein correct answers are penalized and incorrect answers are rewarded. For the
      most prominent class of IRT models, the class of linearly compensatory models, a
      general derivation of paradoxical scoring effects based on the geometry of item
      discrimination vectors is given, which furthermore corrects an error in an
      established theorem on paradoxical results. This approach highlights the very
      counterintuitive way in which item discrimination parameters (and also factor
      loadings) have to be interpreted in terms of their influence on the latent
      ability estimate. It is proven that, despite the error in the original proof, the
      key result concerning the existence of paradoxical effects remains true-although
      the actual relation to the item parameters is shown to be a more complicated
      function than previous results suggested. The new proof enables further insights
      into the actual mathematical causation of the paradox and generalizes the
      findings within the class of linearly compensatory models.

PMID- 29030751
TI  - Effects of regional perfusion block in healthy and injured lungs.
AB  - BACKGROUND: Severe hypoperfusion can cause lung damage. We studied the effects of
      regional perfusion block in normal lungs and in the lungs that had been
      conditioned by lavage with 500 ml saline and high V T (20 ml kg-1) ventilation.
      METHODS: Nineteen pigs (61.2 +/- 2.5 kg) were randomized to five groups: controls
      (n = 3), the right lower lobe block alone (n = 3), lavage and high V T (n = 4),
      lung lavage, and high V T plus perfusion block of the right (n = 5) or left (n =
      4) lower lobe. Gas exchange, respiratory mechanics, and hemodynamics were
      measured hourly. After an 8-h observation period, CT scans were obtained at 0 and
      15 cmH2O airway pressure. RESULTS: Perfusion block did not damage healthy lungs.
      In conditioned lungs, the left perfusion block caused more edema in the
      contralateral lung (777 +/- 62 g right lung vs 484 +/- 204 g left; p < 0.05) than
      the right perfusion block did (581 +/- 103 g right lung vs 484 +/- 204 g left; p
      n.s.). The gas/tissue ratio, however, was similar (0.5 +/- 0.3 and 0.8 +/- 0.5; p
      n.s.). The lobes with perfusion block were not affected (gas/tissue ratio right
      1.6 +/- 0.9; left 1.7 +/- 0.5, respectively). Pulmonary artery pressure,
      PaO2/FiO2, dead space, and lung mechanics were more markedly affected in animals
      with left perfusion block, while the gas/tissue ratios were similar in the non
      occluded lobes. CONCLUSIONS: The right and left perfusion blocks caused the same
      "intensity" of edema in conditioned lungs. The total amount of edema in the two
      lungs differed because of differences in lung size. If capillary permeability is
      altered, increased blood flow may induce or increase edema.

PMID- 29030752
TI  - Sphingorhabdus buctiana sp. nov., isolated from fresh water, and reclassification
      of Sphingopyxis contaminans as Sphingorhabdus contaminans comb. nov.
AB  - A Gram-stain-negative, strictly aerobic, non-motile and rod-shaped bacterial
      strain, designated T5T, was isolated from the Chishui River in Maotai town,
      Guizhou Province, Southwest of China. Strain T5T was found to grow optimally at
      pH 9.0 and 25  degrees C. The 16S rRNA gene sequence analysis indicated that
      strain T5T belongs to the family Sphingomonadaceae within the phylum
      Proteobacteria; the strain T5T clustered with the type strains of Sphingopyxis
      contaminans, Sphingorhabdus wooponensis and Sphingorhabdus rigui, with which it
      exhibits 16S rRNA gene sequence similarity values of 96.2-96.9%. The DNA G+C
      content was 58.5 mol%. The major respiratory quinone was Q-10 and the major polar
      lipid was phosphatidylethanolamine. The major polyamine was homospermidine and
      the major fatty acids were C18:1 omega7c (37.5%) and C16:1 omega7c (30.1%). On
      the basis of phylogenetic, phenotypic and genetic data, strain T5T represents a
      novel species of the genus Sphingorhabdus, for which the name Sphingorhabdus
      buctiana sp. nov. is proposed. The type strain is T5T (= CGMCC 1.12929T = JCM
      30114T). It is also proposed that Sphingopyxis contaminans should be reclassified
      as a member of the genus Sphingorhabdus.

PMID- 29030753
TI  - Successful implementation of Virtual Environment for Radiotherapy Training (VERT)
      in Medical Physics education: The University of Sydney's initial experience and
      recommendations.
AB  - This report outlines the University of Sydney's initial experience with the
      Virtual Environment for Radiotherapy Training (VERT) system in the Master of
      Medical Physics program. VERT is a commercially available system, simulating
      linear accelerators, patient computed tomography (CT) sets, plans and treatment
      delivery. It was purpose built for radiation therapy (RT) education and offers
      learners the opportunity to gain knowledge and skills within an interactive, risk
      free environment. The integration of VERT into the RT physics module of the
      Master of Medical Physics program was intended to enhance student knowledge and
      skills relevant to the curriculum's learning objectives, and to alleviate some of
      the burden associated with student access to clinical equipment. Three VERT
      practical sessions were implemented: "RT treatment planning systems", "(CT)
      Anatomy for physicists" and "Linear accelerator measurements". Our experience and
      student evaluations were positive and demonstrated the viability of VERT for
      medical physics (MP) student education. We anticipate that integration of VERT
      into MP teaching is a valuable addition to traditional methods and can aid MP
      students' understanding and readiness for practice. Additional evaluations should
      be conducted to ascertain VERT's role in delivering efficient quantity and
      quality of MP education, and its potential in alleviating burdens placed on
      clinical departments.

PMID- 29030754
TI  - Postural lung recruitment assessed by lung ultrasound in mechanically ventilated
      children.
AB  - BACKGROUND: Atelectasis is a common finding in mechanically ventilated children
      with healthy lungs. This lung collapse cannot be overcome using standard levels
      of positive end-expiratory pressure (PEEP) and thus for only individualized lung
      recruitment maneuvers lead to satisfactory therapeutic results. In this short
      communication, we demonstrate by lung ultrasound images (LUS) the effect of a
      postural recruitment maneuver (P-RM, i.e., a ventilatory strategy aimed at
      reaerating atelectasis by changing body position under constant ventilation).
      RESULTS: Data was collected in the operating room of the Hospital Privado de
      Comunidad, Mar del Plata, Argentina. Three anesthetized children undergoing
      mechanical ventilation at constant settings were sequentially subjected to the
      following two maneuvers: (1) PEEP trial in the supine position PEEP was increased
      to 10 cmH2O for 3 min and then decreased to back to baseline. (2) P-RM patient
      position was changed from supine to the left and then to the right lateral
      position for 90 s each before returning to supine. The total P-RM procedure took
      approximately 3 min. LUS in the supine position showed similar atelectasis before
      and after the PEEP trial. Contrarily, atelectasis disappeared in the non
      dependent lung when patients were placed in the lateral positions. Both lungs
      remained atelectasis free even after returning to the supine position.
      CONCLUSIONS: We provide LUS images that illustrate the concept and effects of
      postural recruitment in children. This maneuver has the advantage of achieving
      recruitment effects without the need to elevate airways pressures.

PMID- 29030755
TI  - Social-ecological system responses to Hurricane Sandy in the Hudson-Raritan
      Estuary.
AB  - The impact of Hurricane Sandy on the Hudson-Raritan estuary (HRE) provided a
      valuable case study for exploring interactions between long-term environmental
      degradation, new climatic disturbance stressors, and human behavioral responses.
      We extend previous research on the ecological effects of major storms to compare
      water quality and biological parameters three years before and three years after
      Hurricane Sandy and consider how ecosystem shifts relate to anglers' perceptions.
      Results indicate that water clarity and nutrients returned to pre-storm
      conditions in about one year, while shifts in the biological community, including
      a significant increase in harmful algal species and declines in zooplankton and
      Atlantic menhaden, persisted for multiple years, and anglers continued to fish
      amidst ecosystem decline. Biotic recovery time in the HRE was longer than reports
      for other shallow estuaries frequently disturbed by hurricanes. Ecological and
      social responses suggest that the post-storm regime shifts and continued fishing
      pressure could further environmental degradation.

PMID- 29030756
TI  - A Herald of Plasma Cell Myeloma: A Report of Malignant Plasma Cells Identified in
      Parathyroid Adenoma and a Review of Non-parathyroid Malignancies in Parathyroid
      Glands.
AB  - Involvement of the parathyroid glands by non-parathyroid neoplasia is an
      infrequent event. Rare cases of metastases to the parathyroid gland have been
      reported in parathyroidectomies and autopsies of patients with known solid or
      hematopoietic malignancies. Here, we present a case of atypical clonal plasma
      cells incidentally identified within a parathyroid adenoma resected for
      hyperparathyroidism and hypercalcemia, which served as the sentinel event for a
      subsequent diagnosis of plasma cell myeloma. To our knowledge, this is the only
      reported case of a hematopoietic malignancy involving a parathyroid adenoma and
      the only reported case of malignant hematopoietic cells initially detected in
      parathyroidectomy.

PMID- 29030757
TI  - Hemispheric asymmetry of liking for representational and abstract paintings.
AB  - Although the neural correlates of the appreciation of aesthetic qualities have
      been the target of much research in the past decade, few experiments have
      explored the hemispheric asymmetries in underlying processes. In this study, we
      used a divided visual field paradigm to test for hemispheric asymmetries in men
      and women's preference for abstract and representational artworks. Both male and
      female participants liked representational paintings more when presented in the
      right visual field, whereas preference for abstract paintings was unaffected by
      presentation hemifield. We hypothesize that this result reflects a facilitation
      of the sort of visual processes relevant to laypeople's liking for art
      specifically, local processing of highly informative object features-when
      artworks are presented in the right visual field, given the left hemisphere's
      advantage in processing such features.

PMID- 29030758
TI  - The perceptual wink model of non-switching attentional blink tasks.
AB  - The attentional blink (AB) is a temporary deficit for a second target (T2) when
      that target appears after a first target (T1). Although sophisticated models have
      been developed to explain the substantial AB literature in isolation, the current
      study considers how the AB relates to perceptual dynamics more broadly. We show
      that the time-course of the AB is closely related to the time course of the
      transition from positive to negative repetition priming effects in perceptual
      identification. Many AB tasks involve a switch between a T1 defined in one manner
      and a T2 defined in a different manner. Other AB tasks are non-switching, with
      all targets belonging to the same well-known category (e.g., letter targets
      versus number distractors) or sharing the same perceptual feature. We propose
      that these non-switching AB tasks reflect perceptual habituation for the target
      defining attribute; thus, a 'perceptual wink', with perception of one attribute
      (target identity) undisturbed while perception of another (target detection) is
      impaired. On this account, the immediate benefit following T1 (lag-1 sparing)
      reflects positive repetition priming and the subsequent deficit (the blink)
      reflects negative repetition priming for the realization that a target occurred.
      In developing the perceptual wink model, we extended the nROUSE model of
      perceptual priming to explain the results of two new experiments combining the AB
      and identity repetitions. This establishes important connections between non
      switching AB tasks and perceptual dynamics.

PMID- 29030759
TI  - Localizing semantic interference from distractor sounds in picture naming: A dual
      task study.
AB  - In this study we explored the locus of semantic interference in a novel picture
      sound interference task in which participants name pictures while ignoring
      environmental distractor sounds. In a previous study using this task (Madebach,
      Wohner, Kieseler, & Jescheniak, in Journal of Experimental Psychology: Human
      Perception and Performance, 43, 1629-1646, 2017), we showed that semantically
      related distractor sounds (e.g., BARKINGdog) interfere with a picture-naming
      response (e.g., "horse") more strongly than unrelated distractor sounds do (e.g.,
      DRUMMINGdrum). In the experiment reported here, we employed the psychological
      refractory period (PRP) approach to explore the locus of this effect. We combined
      a geometric form classification task (square vs. circle; Task 1) with the picture
      sound interference task (Task 2). The stimulus onset asynchrony (SOA) between the
      tasks was systematically varied (0 vs. 500 ms). There were three central
      findings. First, the semantic interference effect from distractor sounds was
      replicated. Second, picture naming (in Task 2) was slower with the short than
      with the long task SOA. Third, both effects were additive-that is, the semantic
      interference effects were of similar magnitude at both task SOAs. This suggests
      that the interference arises during response selection or later stages, not
      during early perceptual processing. This finding corroborates the theory that
      semantic interference from distractor sounds reflects a competitive selection
      mechanism in word production.

PMID- 29030760
TI  - Patient-specific dosimetry of 99mTc-HYNIC-Tyr3-Octreotide in children.
AB  - BACKGROUND: Technetium-99m-hydrazinonicotinamide-Tyr3-octreotide (99mTc-HYNIC
      TOC) is recognized as a promising radiopharmaceutical for diagnosing
      neuroendocrine tumors (NETs). However, 99mTc-HYNIC-TOC dosimetry has been
      investigated only for adults. As pediatric radionuclide therapies become
      increasingly common, similar dosimetric studies for children are urgently needed.
      The aim of this study is to report personalized image-based biodistributions and
      dosimetry evaluations for children studies performed using 99mTc-HYNIC-TOC and to
      compare them with those from adult subjects. Eleven children/teenage patients
      with suspected or diagnosed NETs were enrolled. Patient imaging included a series
      of 2-3 whole-body planar scans and SPECT/CT performed over 2-24 h after the 99mTc
      HYNIC-TOC injections. The time-integrated activity coefficients (TIACs) were
      obtained from the hybrid planar/SPECT technique. Patient-specific doses were
      calculated using both the voxel-level and the organ-level approaches. Estimated
      children doses were compared with adults' dosimetry. RESULTS: Pathologic uptake
      was observed in five patients. TIACs for normal organs with significant uptakes,
      i.e., kidneys, spleen, and liver, were similar to adults' TIACs. Using the voxel
      level approach, the average organ doses for children were 0.024 +/- 0.009, 0.032
      +/- 0.017, and 0.017 +/- 0.007 mGy/MBq for the kidneys, spleen, and liver,
      respectively, which were 30% larger than adults' doses. Similar values were
      obtained from the organ-level dosimetry when using OLINDA with adapted organ
      masses. Tumor doses were 0.010-0.024 mGy/MBq. However, cross-organ contributions
      were much larger in children than in adults, comprising about 15-40% of the total
      organ/tumor doses. No statistical differences were found between mean doses and
      dose distributions in patients with and without pathologic uptakes. CONCLUSION:
      Although the children TIACs were similar to those in adults, their doses were
      about 30% higher. No significant correlation was found between the children's
      doses and their ages. However, substantial inter-patient variability in
      radiotracer uptake, indicating disparity in expression of somatostatin receptor
      between different patients, emphasizes the importance and necessity of patient
      specific dosimetry for clinical studies.

PMID- 29030761
TI  - Monitoring the effects of a lepidopteran insecticide, Flubendiamide, on the
      biology of a non-target dipteran insect, Drosophila melanogaster.
AB  - Various organisms are adversely affected when subjected to chronic fluoride
      exposure. This highly electronegative ion present in several insecticide
      formulations is found to be lethal to target pests. In the present study,
      Drosophila melanogaster is treated with sub-lethal concentrations of a diamide
      insecticide formulation, Flubendiamide. Chronic exposure to the diamide (0.5-100
      MUg/mL) was found to be responsible for increase in fluoride ion concentration in
      larval as well as adult body fluid. Interestingly, 100 MUg/mL Flubendiamide
      exposure resulted in 107 and 298% increase in fluoride ion concentration whereas
      only 23 and 52% of Flubendiamide concentration increase in larval and adult body
      fluid, respectively. Further, in this study, selected life cycle parameters like
      larval duration, pupal duration and emergence time showed minimal changes,
      whereas percentage of emergence and fecundity revealed significant treatment
      associated variation. It can be noted that nearly 79% reduction in fecundity was
      observed with 100 MUg/mL Flubendiamide exposure. The variations in these
      parameters indicate probable involvement of fluoride ion in detectable
      alterations in the biology of the non-target model insect, D. melanogaster.
      Furthermore, the outcomes of life cycle study suggest change in resource
      allocation pattern in the treated flies. The altered resource allocation might
      have been sufficient to resist changes in selective life cycle parameters, but it
      could not defend the changes in fecundity. The significant alterations indicate a
      definite trade-off pattern, where the treated individuals happen to compromise.
      Thus, survival is apparently taking an upper hand in comparison to reproductive
      ability in response to Flubendiamide exposure. Graphical abstract The figure
      demonstrates increase in Fluoride and Flubendiamide concentrations in Drosophila
      melanogaster after chronic sub-lethal exposure to Flubendiamide. Treatment
      induced alterations in larval and pupal duration, reduction in fecundity and
      alteration in male-female ratio is also observed.

PMID- 29030762
TI  - Genetic diversity of avenin-like b genes in Aegilops tauschii Coss.
AB  - Avenin-like storage proteins influence the rheological properties and processing
      quality in common wheat, and the discovery of new alleles will benefit wheat
      quality improvement. In this study, 13 avenin-like b alleles (TaALPb7D-A-M) were
      discovered in 108 Aegilops tauschii Coss. accessions. Ten alleles were reported
      for the first time, while the remaining three alleles were the same as alleles in
      other species. A total of 15 nucleotide changes were detected in the 13 alleles,
      resulting in only 11 amino acid changes because of synonymous mutations. Alleles
      TaALPb7D-E, TaALPb7D-G, and TaALPb7D-J encoded the same protein. These
      polymorphic sites existed in the N-terminus, Repetitive region (Left), Repetitive
      region (Right) and C-terminus domains, with no polymorphisms in the signal
      peptide sequence nor in those encoding the 18 conserved cysteine residues.
      Phylogenetic analysis divided the TaALPb7Ds into four clades. The Ae. tauschii
      alleles were distributed in all four clades, while the alleles derived from
      common wheat, TaALPb7D-G and TaALPb7D-C, belonged to clade III and IV,
      respectively. Alleles TaALPb7D-G and TaALPb7D-C were the most widely distributed,
      being present in nine and six countries, respectively. Iran and Turkey exhibited
      the highest genetic diversity with respect to TaALPb7D alleles, accessions from
      these countries carrying seven and six alleles, respectively, which implied that
      these countries were the centers of origin of the avenin-like b gene. The new
      alleles discovered and the phylogenetic analysis of avenin-like b genes will
      provide breeding materials and a theoretical basis for wheat quality improvement.

PMID- 29030763
TI  - Conservation and genetic characterisation of common bean landraces from Cilento
      region (southern Italy): high differentiation in spite of low genetic diversity.
AB  - Since its introduction from Central-South America to Italy almost 500 years ago,
      the common bean (Phaseolus vulgaris L.) was largely cultivated across the
      peninsula in hundreds of different landraces. However, globalisation and
      technological modernisation of agricultural practices in the last decades
      promoted the cultivation of few varieties at the expense of traditional and local
      agro-ecotypes, which have been confined to local markets or have completely
      disappeared. The aim of this study was to evaluate the genetic diversity and
      differentiation in 12 common bean landraces once largely cultivated in the
      Cilento region (Campania region, southern Italy), and now the object of a
      recovery program to save them from extinction. The analysis conducted using 13
      nuclear microsatellite loci in 140 individuals revealed a high degree of
      homozygosity within each landrace and a strong genetic differentiation that was
      reflected in the success in assigning individuals to the source landrace. On the
      contrary, internal transcribed spacers 1 and 2, analysed in one individual per
      landrace, were highly similar among common bean landraces but allowed the
      identification of a cowpea variety (Vigna unguiculata Walp.), a crop largely
      cultivated in the Old World before the arrival of common bean from Americas. In
      conclusion, our study highlighted that conservation of landraces is important not
      only for the cultural and socio-economic value that they have for local
      communities, but also because the time and conditions in which they have been
      selected have led to that genetic distinctiveness that is at the basis of many
      potential agronomical applications and dietary benefits.

PMID- 29030764
TI  - Effect of including a gas layer on the gel formation process during the drying of
      a polymer solution.
AB  - In this paper, we study the influence of the upper gas layer on the drying and
      gelation of a polymer solution. The gel is formed due to the evaporation of the
      binary solution into (inert) air. A one-dimensional model is proposed, where the
      evaporation flux is more realistically described than in previous studies. The
      approach is based on general thermodynamic principles. A composition-dependent
      diffusion coefficient is used in the liquid phase and the local equilibrium
      hypothesis is introduced at the interface to describe the evaporation process.
      The results show that the high thickness of the gas layer reduces evaporation,
      thus leading to longer drying times. Our model is also compared with more
      phenomenological descriptions of evaporation, for which the mass flux through the
      interface is described by the introduction of a Peclet number. A global agreement
      is found for appropriate values of the Peclet numbers and our model can thus be
      considered as a tool allowing to link the value of the empirical Peclet number to
      the physics of the gas phase. Finally, in contrast with other models, our
      approach emphasizes the possibility of very fast gelation at the interface, which
      could prevent all Marangoni convection during the drying process.

PMID- 29030765
TI  - Cerebrospinal fluid analysis and the determination of oligoclonal bands.
AB  - This document presents the guidelines for the cerebrospinal fluid (CSF) analysis
      and the determination of oligoclonal bands (OCBs) as pivotal tests in
      neuroinflammatory pathologies of the central nervous system. The guidelines have
      been developed following a consensus process built on questionnaire-based
      surveys, internet contacts, and discussions at workshops of the sponsoring
      Italian Association of Neuroimmunology (AINI) congresses. Essential clinical
      information on the pathologies in which the CSF analysis is indicated, and,
      particularly, on those characterized by the presence of OCBs in the intrathecal
      compartment, indications and limits of CSF analysis and OCB determination,
      instructions for result interpretation, and agreed laboratory protocols
      (Appendix) are reported for the communicative community of neurologists and
      clinical pathologists.

PMID- 29030766
TI  - Diagnostics of paraneoplastic neurological syndromes.
AB  - This document presents the guidelines for onconeural antibody testing that have
      been developed following a consensus process built on questionnaire-based
      surveys, internet contacts, and discussions at workshops of the sponsoring
      Italian Association of Neuroimmunology (AINI) congresses. Essential clinical
      information on paraneoplastic neurological syndromes, indications and limits of
      onconeural antibody testing, instructions for result interpretation, and an
      agreed laboratory protocol (Appendix) are reported for the communicative
      community of neurologists and clinical pathologists.

PMID- 29030767
TI  - Diagnostics of autoimmune encephalitis associated with antibodies against
      neuronal surface antigens.
AB  - This document presents the guidelines for testing antibodies against neuronal
      surface antigens that have been developed following a consensus process built on
      questionnaire-based surveys, internet contacts, and discussions at workshops of
      the sponsoring Italian Association of Neuroimmunology (AINI) congresses.
      Essential clinical information on autoimmune encephalitis associated with
      antibodies against neuronal surface antigens, indications and limits of testing
      for such antibodies, instructions for result interpretation, and an agreed
      laboratory protocol (Appendix A) are reported for the communicative community of
      neurologists and clinical pathologists.

PMID- 29030768
TI  - Diagnostics of the neuromyelitis optica spectrum disorders (NMOSD).
AB  - This document presents the guidelines for anti-aquaporin-4 (AQP4) antibody
      testing that has been developed following a consensus process built on
      questionnaire-based surveys, internet contacts, and discussions at workshops of
      the sponsoring Italian Association of Neuroimmunology (AINI) congresses.
      Essential clinical information on neuromyelitis optica spectrum disorders,
      indications and limits of anti-AQP4 antibody testing, instructions for result
      interpretation, and an agreed laboratory protocol (Appendix) are reported for the
      communicative community of neurologists and clinical pathologists.

PMID- 29030769
TI  - Diagnostics of dysimmune peripheral neuropathies.
AB  - This document presents the guidelines for anti-ganglioside antibody testing that
      have been developed following a consensus process built on questionnaire-based
      surveys, internet contacts, and discussions at workshops of the sponsoring
      Italian Association of Neuroimmunology (AINI) congresses. Main clinical
      information on dysimmune peripheral neuropathies, indications and limits of anti
      ganglioside antibody testing, instructions for result interpretation, and an
      agreed laboratory protocol (Appendix) are reported for the communicative
      community of neurologists and clinical pathologists.

PMID- 29030770
TI  - Diagnostics of myasthenic syndromes: detection of anti-AChR and anti-MuSK
      antibodies.
AB  - This paper presents the Italian guidelines for autoantibody testing in myasthenia
      gravis that have been developed following a consensus process built on
      questionnaire-based surveys, internet contacts and discussions during dedicated
      workshops of the sponsoring Italian Association of Neuroimmunology (AINI).
      Essential clinical information on myasthenic syndromes, indications and limits of
      antibody testing, instructions for result interpretation and an agreed laboratory
      protocol (Appendix) are reported for the communicative community of neurologists
      and clinical pathologists.

PMID- 29030771
TI  - A bridge between evidence-based laboratory diagnostics and research in
      neuroimmunology: why standardizations and guidelines matter.

PMID- 29030772
TI  - Diagnostics of anti-MAG antibody polyneuropathy.
AB  - This document presents the guidelines for anti-myelin-associated glycoprotein
      (MAG) antibody testing that have been developed following a consensus process
      built on questionnaire-based surveys, internet contacts, and discussions at
      workshops of sponsoring Italian Association of Neuroimmunology (AINI) congresses.
      The main clinical information on anti-MAG antibody polyneuropathy, indications
      and limits of anti-MAG antibody testing, instructions for result interpretation,
      and an agreed laboratory protocol (Appendix) are reported for the communicative
      community of neurologists and clinical pathologists.

PMID- 29030773
TI  - Outcome prediction with the revised American joint committee on cancer staging
      system and American thyroid association guidelines for thyroid cancer.
AB  - BACKGROUND: Several staging systems have been developed to predict the risk of
      mortality in patients with differentiated thyroid cancer (DTC). However, none of
      them have been shown to be clearly superior to the other. METHODS: We compared
      the patient outcome predictability of recently revised staging systems
      predictability of patient outcome using data from The Cancer Genome Atlas. To set
      a comparison among American Joint Committee on Cancer (AJCC)/Union for
      International Cancer Control (UICC) staging 7th, 8th editions, American Thyroid
      Association guidelines 2009 and 2015, concordance index (c-index), Akaike
      information criterion (AIC), Bayesian information criterion (BIC), and Brier
      score were applied to quantify the predictive ability of a survival model, to
      select the statistical model, and to measure the accuracy of probabilistic
      predictions. RESULTS: A total of 457 patients with papillary thyroid cancer
      having a mean age of 45.9 years were included in this study (120 males, 337
      females). Among these patients, 43 (9.4%) experienced recurrence/progression
      during the follow-up (591.2 +/- 833.5 months). Among the models used, the
      AJCC/UICC 8th edition, which showed the highest c-index and lowest AIC, BIC, and
      Brier score, was identified as the best among the models used. CONCLUSION:
      AJCC/UICC 8th edition predicted patient outcome more accurately than the other
      staging systems.

PMID- 29030774
TI  - Effects of growth hormone therapy on bone density and fracture risk in age
      related osteoporosis in the absence of growth hormone deficiency: a systematic
      review and meta-analysis.
AB  - PURPOSE: In adults, growth hormone deficiency (GHD) has been associated with low
      bone mineral density (BMD), an effect counteracted by growth hormone (GH)
      replacement. Whether GH is beneficial in adults with age-related bone loss and
      without hypopituitarism is unclear. METHODS: We conducted a systematic literature
      search using Medline, Embase and the Cochrane Register of Controlled Trials. We
      extracted and analyzed data according to the bone outcome included [bone mineral
      content (BMC), BMD, and bone biomarker, fracture risk]. We performed a meta
      analysis when possible. RESULTS: We included eight studies. Seven randomized 272
      post-menopausal women, 61-69 years, to GH or control, for 6-24 months, and the
      eighth was an extension trial. Except for one study, all women received
      concurrent osteoporosis therapies. There was no significant effect of GH, as
      compared to control, on BMD at the lumbar spine (Weighted mean difference WMD = 
      0.01 [-0.04, 0.02]), total hip (WMD = 0 [-0.05, 0.06]) or femoral neck (WMD = 0 [
      0.03, 0.04]). Similarly, no effect was seen on BMC. GH significantly increased
      the bone formation marker procollagen type-I carboxy-terminal propeptide (PICP)
      (WMD = 14.03 [2.68, 25.38]). GH resulted in a trend for increase in osteocalcin
      and in bone resorption markers. Patients who received GH had a significant
      decrease in fracture risk as compared to control (RR = 0.63 [0.46, 0.87]).
      Reported adverse events were not major, mostly related to fluid retention.
      CONCLUSION: GH may not improve bone density in women with age-related bone loss
      but may decrease fracture risk. Larger studies of longer duration are needed to
      further explore these findings in both genders, and to investigate the effect of
      GH on bone quality.

PMID- 29030775
TI  - Improvement in pregnancy outcomes in couples with immunologically male
      infertility undergoing prednisolone treatment and conventional in vitro
      fertilization preceded by sperm penetration assay: a randomized controlled trial.
AB  - PURPOSE: Anti-sperm antibodies (ASA) in men impair not only sperm motility but
      also fertilization and conception. However, utilization of corticosteroids to
      suppress ASA has shown variable pregnancy outcomes. This controversy is also
      extended to include the usefulness of conventional in vitro fertilization (IVF)
      and intracytoplasmic sperm injection (ICSI) in treatments of men with ASA. This
      study was therefore designed to define factors contributing to these inconsistent
      results. METHODS: Infertile men having ASA (n = 241) were randomly assigned for
      treatment with or without prednisolone for three cycles each of 21 days of their
      partner's menstrual cycles. Control and treated men underwent then human sperm
      penetration assay (SPA), of hamster oocytes, to diagnose men with impaired sperm
      fusogenic capacity. Men with positive or negative SPA results were admitted to
      conventional IVF or ICSI programs, respectively. RESULTS: Treated patients had
      improved sperm motility and progressive motility when compared to control
      patients (P < 0.001). Fertilization (P = 0.04), embryo cleavage (P = 0.01), and
      chemical (P = 0.02) and clinical (P = 0.04) pregnancy rates were higher in
      treated patients than in control patients undergoing conventional IVF but not
      ICSI cycles. CONCLUSIONS: Men with ASA may also have compromised sperm fusogenic
      capacity, which can mask the clinical significance of corticosteroids.
      Corticosteroid administration in men with ASA, but without compromised sperm
      fusogenic capacity, improves conventional IVF but not ICSI outcomes; the reason
      being that ICSI bypasses issues of compromised fusogenic capacity. Inclusion of
      SPA in infertility clinics that offer both conventional IVF and ICSI services may
      be useful to identify which patients with ASA benefit from corticosteroid
      treatments.

PMID- 29030776
TI  - Oscillations of Cerium Oxidation State Driven by Oxygen Diffusion in Colloidal
      Nanoceria (CeO2 - x ).
AB  - The redox performance of CeO2 - x nanocrystals (nanoceria) is always accompanied
      by the switching of cerium oxidation state between Ce3+ and Ce4+. We monitored
      Ce3+ -> Ce4+ oxidation of nanoceria stimulated by oxidant in aqueous colloidal
      solutions controlling the luminescence of Ce3+ ions located at different
      distances from nanoceria surface. The observed Ce3+ luminescence changes indicate
      that Ce3+ -> Ce4+ reaction develops inside nanoceria being triggered by the
      diffusing oxygen originated from the water splitting on oxidized nanoceria
      surface. We present the first observation of the pronounced oscillations of Ce3+
      luminescence intensity arising from Ce3+ <-> Ce4+ reversible switching. This
      threshold effect is to be driven by uptaking and releasing oxygen by nanoceria,
      when the concentration of oxygen vacancies in nanoceria lattice, oxidant
      concentration in colloidal solution, and temperature reach certain critical
      values. So, the ability of nanoceria to uptake and release oxygen depending on
      the environmental redox conditions really makes it the self-sufficient eternal
      antioxidant.

PMID- 29030777
TI  - Energy transfer and trapping in Synechococcus WH 7803.
AB  - Excitation energy transfer (EET) and trapping in Synechococcus WH 7803 whole
      cells and isolated photosystem I (PSI) complexes have been studied by time
      resolved emission spectroscopy at room temperature (RT) and at 77 K. With the
      help of global and target analysis, the pathways of EET and the charge separation
      dynamics have been identified. Energy absorbed in the phycobilisome (PB) rods by
      the abundant phycoerythrin (PE) is funneled to phycocyanin (PC645) and from there
      to the core that contains allophycocyanin (APC660 and APC680). Intra-PB EET rates
      have been estimated to range from 11 to 68/ns. It was estimated that at RT, the
      terminal emitter of the phycobilisome, APC680, transfers its energy at a rate of
      90/ns to PSI and at a rate of 50/ns to PSII. At 77 K, the redshifted Chl a states
      in the PSI core were heterogeneous, with maximum emission at 697 and 707 nm. In
      72% of the PSI complexes, the bulk Chl a in equilibrium with F697 decayed with a
      main trapping lifetime of 39 ps.

PMID- 29030778
TI  - Acceleration of the excitation decay in Photosystem I immobilized on glass
      surface.
AB  - Femtosecond transient absorption was used to study excitation decay in monomeric
      and trimeric cyanobacterial Photosystem I (PSI) being prepared in three states:
      (1) in aqueous solution, (2) deposited and dried on glass surface (either
      conducting or non-conducting), and (3) deposited on glass (conducting) surface
      but being in contact with aqueous solvent. The main goal of this contribution was
      to determine the reason of the acceleration of the excitation decay in dried PSI
      deposited on the conducting surface relative to PSI in solution observed
      previously using time-resolved fluorescence (Szewczyk et al., Photysnth Res
      132(2):111-126, 2017). We formulated two alternative working hypotheses: (1) the
      acceleration results from electron injection from PSI to the conducting surface;
      (2) the acceleration is caused by dehydration and/or crowding of PSI proteins
      deposited on the glass substrate. Excitation dynamics of PSI in all three types
      of samples can be described by three main components of subpicosecond, 3-5, and
      20-26 ps lifetimes of different relative contributions in solution than in PSI
      substrate systems. The presence of similar kinetic components for all the samples
      indicates intactness of PSI proteins after their deposition onto the substrates.
      The kinetic traces for all systems with PSI deposited on substrates are almost
      identical and they decay significantly faster than the kinetic traces of PSI in
      solution. We conclude that the accelerated excitation decay in PSI-substrate
      systems is caused mostly by dense packing of proteins.

PMID- 29030779
TI  - Recurrence After Operative Treatment of Adhesive Small-Bowel Obstruction.
AB  - BACKGROUND: Postoperative adhesions are a common cause of small-bowel
      obstruction, and up to 53% of patients operated on for adhesive small-bowel
      obstruction (ASBO) experience recurrence. The primary aim of this study was to
      identify predictors for recurrence of ASBO. METHODS: We reviewed medical records
      including operation descriptions from patients who underwent emergency surgery
      due to ASBO at our institution between 2004 and 2013. Information on the peri-
      and postoperative periods, including conservatively and surgically treated
      recurrent ASBO, were obtained from medical records. RESULTS: In total, 478
      patients were included in the study. Of these, 58 (12.1%) patients experienced
      recurrence of ASBO during median 2.2 years follow-up. Female gender (hazard ratio
      [HR] 2.00, P = 0.023), multiple/matted adhesions (HR 1.72, P = 0.046), and
      fascial dehiscence (HR 3.26, P = 0.009) were associated with increased risk of
      recurrence. Conversely, intestinal resection decreased the risk of recurrence (HR
      0.47, P = 0.036). CONCLUSIONS: The overall recurrence rate after surgically
      treated ASBO was 12.1%, and the risk of recurrence was persistent several years
      after index operation. Factors associated with an increased risk were female
      gender, multiple/matted adhesions, and fascial dehiscence.

PMID- 29030780
TI  - Endoscopic Treatment Versus Esophagectomy for Early-Stage Esophageal Cancer: a
      Population-Based Study Using Propensity Score Matching.
AB  - BACKGROUND: Endoscopic treatment (ET) is an alternative for selected patients
      with early-stage esophageal cancer. The primary aim of this study was to compare
      overall survival (OS) and esophageal cancer-specific survival (ECSS) of such
      patients after ET or esophagectomy. METHODS: Propensity score matching (PSM) and
      Cox regression analysis were used to compare OS and ECSS of 2661 patients with ET
      or esophagectomy for early-stage (Tis-T1N0M0) disease. Patient information was
      retrieved from the Surveillance, Epidemiology, and End Results database. Subgroup
      analyses by T stage and tumor histology were also performed. RESULTS: There were
      significant differences in age, sex ratio, year of diagnosis, cancer site, cancer
      stage, differentiation grade, tumor histology, tumor size, lymph nodes examined,
      and receipt of radiation therapy in the two treatment groups. PSM created 621
      patient pairs. Multivariate analysis found no significant differences in OS (HR =
      1.216, P = 0.279) or ECSS (HR = 0.692, P = 0.179) in the esophagectomy and ET
      groups. The results were similar for subgroup analyses limited to stage Tis, T1a,
      and T1b patients. ET was also associated with similar OS and ECSS in esophageal
      adenocarcinoma and squamous cell carcinoma patients. CONCLUSION: In this
      population-based study using PSM, patients with stage Tis and T1N0M0 esophageal
      cancer with ET had OS and ECSS comparable to those treated by esophagectomy after
      adjusting for clinical variables. The results support ET as an alternative to
      esophagectomy in early esophageal cancer.

PMID- 29030781
TI  - Clinical and imaging features in lung torsion and description of a novel imaging
      sign.
AB  - PURPOSE: We set out to identify the clinical and imaging features seen in lung
      torsion, a rare but emergent diagnosis leading to vascular compromise of a lobe
      or entire lung. METHODS: We retrospectively identified 10 patients with torsion
      who underwent chest CT. We evaluated each case for the presence of bronchial
      obstruction and abnormal fissure orientation. In seven patients who underwent
      contrast-enhanced CTs, we assessed for the presence of the antler sign, a novel
      sign seen on axial images demonstrating abnormal curvature of the artery and
      branches originating on one side. RESULTS: Five patients had right middle lobe
      (RML) torsion after right upper lobectomy, and the remaining occurred following
      thoracentesis, aortic surgery, or spontaneously. Chest CTs demonstrated bronchial
      obstruction in eight cases and presence of abnormal fissure orientation in four
      patients. The antler sign was present in three patients with whole-lung torsion
      and one patient with lobar torsion; vascular swirling was seen on 3-D images in
      all seven patients with contrast-enhanced CTs. CONCLUSIONS: Lung parenchymal
      imaging findings in lung torsion may be non-specific. Identification of the
      antler sign on contrast-enhanced chest CT, in combination with other signs such
      as bronchial obstruction and abnormal fissure orientation, indicates rotation of
      the bronchovascular pedicle. The presence of this sign should prompt further
      evaluation with 3-dimensional reconstructions.

PMID- 29030782
TI  - Does radiography still have a significant diagnostic role in evaluation of acute
      traumatic wrist injuries? A prospective comparative study.
AB  - AIM: The aim of this study was to evaluate and compare the diagnostic role of
      radiography and multi-detector computed tomography (MDCT) in acute traumatic
      wrist injuries. PATIENTS AND METHODS: One hundred sixty-eight patients with acute
      wrist trauma were enrolled in our study. All patients had submitted to
      radiography and MDCT within 24 h after wrist trauma. The diagnostic role of
      radiography and MDCT was evaluated and compared. The effective radiation dose of
      the two techniques was calculated. RESULTS: One hundred four (61.9%) and 84 (50%)
      out of 168 patients had acute wrist injuries on MDCT and radiographic
      examinations, respectively. Using MDCT results as a reference standard, the
      sensitivity, specificity, and accuracy of radiography in the diagnosis of distal
      radius fracture were 85.7, 96, and 92.3%, respectively, and in the diagnosis of
      scaphoid fracture were 62.5, 97.3, and 88.5%, respectively. As regards detection
      of acute traumatic wrist injuries, we observed no significant difference between
      the two modalities (P = 0.1347); in addition, both modalities had high
      consistency (kappa = 0.8359). The mean effective radiation dose of radiography
      was 0.01 mSv and of MDCT was 0.1 mSv. CONCLUSION: Radiography still remains as
      the first screening tool in acute traumatic wrist injuries and MDCT is
      complementary to it and used as a problem-solving tool or for preoperative
      planning.

PMID- 29030783
TI  - The Head, the Heart, and Hysteria in Jeanne Flore's Tales and Trials of Love (c.
      1542).
AB  - This essay examines a challenge to common literary representations of female
      mental illness in the Early Modern period-the hysterical woman-in a collection of
      French short stories contemporary to Vesalius's De Fabrica: Jeanne Flore's Tales
      and Trials of Love (1542). Jeanne Flore's tales depict several mentally disturbed
      female protagonists, young women prone to paroxysms of madness and self
      mutilation. This study maintains that while Tales and Trials of Love
      superficially participates in the literary tradition that grew out of those
      accepted social and medical beliefs, it also questions the long-accepted paradigm
      of female hysteria and points to a shift in the socio-medical climate. Jeanne
      Flore's fictional narratives suggest that mental illness no longer consists in
      the realignment of a uterine imbalance, but rather in the telling of personal
      stories, a precursor to psychoanalysis and narrative medicine.

PMID- 29030784
TI  - Anti-TNF-alpha antibody alleviates insulin resistance in rats with sepsis-induced
      stress hyperglycemia.
AB  - PURPOSE: To explore the effects and mechanisms of anti-tumor necrosis factor
      alpha (TNF-alpha) antibody on insulin resistance (IR) in rats with sepsis-induced
      stress hyperglycemia. METHODS: The sepsis-induced stress hyperglycemic rat model
      was constructed by cecal ligation and puncture combined with the intraperitoneal
      injection of lipopolysaccharide. The rats were randomly divided into six groups:
      normal control (NC) group, surgical rats (Cntl) group, high-dose anti-TNF-alpha
      antibody therapy (TNF, 6 mg/kg) group, low-dose anti-TNF-alpha antibody therapy
      (Tnf, 3 mg/kg) group, insulin therapy (INS) group, and INS + Tnf group. The blood
      glucose and serum insulin concentrations were detected, followed by analysis of
      intraperitoneal glucose tolerance test (IPGTT) and hyperinsulinemic-euglycemic
      clamp. Finally, the expression levels of phospho-Akt (p-Akt), Akt, p-mTOR, mTOR,
      nuclear factor-kappaB (NFkappaB), I kappa beta kinase (IKKbeta), and suppressor
      of cytokine signaling (SOCS-3) were detected by western blotting. RESULTS: There
      was no significant difference in blood glucose concentrations among these groups,
      while the serum insulin concentration in TNF and Tnf groups was lower than that
      in the Cntl group at postoperative 6 h (P < 0.05). IPGTT analysis revealed that
      blood glucose level was lower in the TNF group than that in the Cntl group (P <
      0.05). The glucose infusion rate in the Cntl group was lower than that in the Tnf
      and TNF groups (P < 0.05). The p-Akt/Akt, p-mTOR/mTOR ratio, and expression
      levels of NFkappaB, IKKbeta and SOCS-3 were lower in the drug intervention than
      that in the Cntl group (P < 0.05). CONCLUSIONS: Anti-TNF-alpha antibody could
      reduce IR by inhibiting AKt/mTOR signaling pathway and the expression levels of
      NFkappaB, IKKbeta, and SOCS-3 in rats with sepsis-induced stress hyperglycemia.

PMID- 29030785
TI  - Usefulness of abbreviated breast MRI screening for women with a history of breast
      cancer surgery.
AB  - PURPOSE: We investigated the usefulness of abbreviated breast MRI (AB-MRI),
      including fat-suppressed T2-weighted imaging, pre- and postcontrast image
      acquisition, and subtracted maximum-intensity projection imaging, for the
      screening of women with a history of breast cancer surgery. METHODS: Between
      October 2014 and March 2016, a total of 799 AB-MRI examinations were performed
      for 725 women with a history of breast cancer surgery. The image acquisition time
      was 8.5 min. Screening mammography, ultrasound, and AB-MRI were generally
      performed around the same time. The cancer detection rate, positive predictive
      values for recall and biopsy, sensitivity and specificity of screening MRI, and
      rate of malignancy belonging to each breast imaging reporting and data system (BI
      RADS) category were assessed. RESULTS: AB-MRI detected 12 malignancies in 12
      women (15.0 cancers per 1000 cases). Seven of these 12 malignancies were
      initially invisible on ultrasound and mammography, although subsequent targeted
      ultrasound revealed lesions corresponding to the MRI-detected lesions. The
      positive predictive values for recall and biopsy and sensitivity and specificity
      values for screening MRI were 12.4, 61.5, 100, and 89.2%, respectively. The rates
      of malignancies belonging to categories 1, 2, 3, and 4 of the BI-RADS were 0, 0,
      4.8, and 57.1%, respectively. CONCLUSIONS: The diagnostic performance of
      screening AB-MRI for women with a history of breast cancer surgery is acceptable,
      with the advantages of short examination and interpretation times and low costs.
      Thus, it could be used as a main screening modality that may replace conventional
      imaging in breast cancer survivors.

PMID- 29030786
TI  - Routine treatment and outcome of breast cancer in younger versus elderly
      patients: results from the SENORA project of the prospective German TMK cohort
      study.
AB  - PURPOSE: There is an ongoing discussion about 'undertreatment' of breast cancer
      in elderly patients. Due to low accrual into clinical trials, level 1 evidence is
      scarce. We report prospective data of elderly patients with breast cancer treated
      by medical oncologists in Germany. METHODS: The SENORA project within the
      prospective cohort study TMK (Tumour Registry Breast Cancer) was conducted in 82
      centres from 2007-2015. Among 2316 patients, half were enrolled with curative and
      half with palliative treatment intention. Overall, 478 patients (21%) were aged
      >= 70. RESULTS: In the adjuvant setting, elderly patients aged >= 70 had more
      advanced tumour stages at diagnosis and a higher prevalence of comorbidities than
      younger patients. Elderly patients received adjuvant chemotherapy less
      frequently, yet the 3-year disease-free survival was similar (86% vs. 88%). In
      the palliative setting, elderly patients more frequently received endocrine
      therapy and less frequently chemotherapy. Their median overall survival [24.9
      months, 95% CI (confidence interval) 20.0-30.2] was significantly shorter than
      that of younger patients (39.7 months, 95% CI 34.9-44.2). A Cox proportional
      hazards model showed a significantly increased risk of mortality for: age >= 70
      at start of therapy, negative HR- or HER2-status, higher number of metastatic
      sites, more comorbidities and high tumour grading at diagnosis. CONCLUSIONS: Our
      results shed light on the routine treatment of elderly patients with breast
      cancer. A regression model demonstrated that age is but one of various prognostic
      factors determining the shorter overall survival of elderly patients.

PMID- 29030787
TI  - Armillifer-Infected Snakes Sold at Congolese Bushmeat Markets Represent an
      Emerging Zoonotic Threat.
AB  - African pythons (Pythonidae) and large vipers (Bitis spp.) act as definitive
      hosts for Armillifer armillatus and Armillifer grandis parasites (Crustacea:
      Pentastomida) in the Congo Basin. Since the proportion of snakes in bushmeat
      gradually increases, human pentastomiasis is an emerging zoonotic disease. To
      substantiate the significance of this threat, we surveyed snakes offered for
      human consumption at bushmeat markets in the Kole district, Democratic Republic
      of the Congo, for the presence of adult pentastomids. In Bitis vipers (n = 40),
      Armillifer spp. infestations exhibited an 87.5% prevalence and 6.0 median
      intensity. Parasite abundance covaried positively with viper length, but not with
      body mass. In pythons (n = 13), Armillifer spp. exhibited a 92.3% prevalence and
      3.5 median intensity. The positive correlations between parasite abundance and
      python length or mass were statistically nonsignificant. Ninety-one percent of A.
      grandis were discovered in vipers and 97% of infected vipers hosted A. grandis,
      whereas 81% of A. armillatus specimens were found in pythons and 63% of infected
      pythons hosted A. armillatus. Thus, challenging the widespread notion of strict
      host specificity, we found 'reversed' infections and even a case of coinfection.
      In this study, we also gathered information about the snake consumption habits of
      different tribal cultures in the area. Infective parasite ova likely transmit to
      humans directly by consumption of uncooked meat, or indirectly through
      contaminated hands, kitchen tools or washing water.

PMID- 29030788
TI  - Viral Richness is Positively Related to Group Size, but Not Mating System, in
      Bats.
AB  - Characterizing host traits that influence viral richness and diversification is
      important for understanding wildlife pathogens affecting conservation and/or
      human health. Behaviors that affect contact rates among hosts could be important
      for viral diversification because more frequent intra- and inter-specific
      contacts among hosts should increase the potential for viral diversification
      within host populations. We used published data on bats to test the contact-rate
      hypothesis. We predicted that species forming large conspecific groups, that
      share their range with more heterospecifics (i.e., sympatry), and with mating
      systems characterized by high contact rates (polygynandry: multi-male/multi
      female), would host higher viral richness than species with small group sizes,
      lower sympatry, or low contact-rate mating systems (polygyny: single male/multi
      female). Consistent with our hypothesis and previous research, viral richness was
      positively correlated with conspecific group size although the relationship
      plateaued at group sizes of approximately several hundred thousand bats. This
      pattern supports epidemiological theory that, up to a point, larger groups have
      higher contact rates, greater likelihood of acquiring and transmitting viruses,
      and ultimately greater potential for viral diversification. However, contrary to
      our hypothesis, there was no effect of sympatry on viral richness and no
      difference in viral richness between mating systems. We also found no residual
      effect of host phylogeny on viral richness, suggesting that closely related
      species do not necessarily host similar numbers of viruses. Our results support
      the contact-rate hypothesis that intra-specific viral transmission can enhance
      viral diversification within species and highlight the influence of host group
      size on the potential of viruses to propagate within host populations.

PMID- 29030789
TI  - Foreign bodies in sigmoid colon diverticulosis.
AB  - This review addresses the management of sigmoid colon diverticular disease
      associated with foreign bodies. In addition, two novel cases are presented. One
      case describes the management of diverticular bleeding secondary to a chicken
      bone and the other case reports retrieval of a retained EndoRingsTM Device. The
      review identified 40 relevant publications including 50 subjects. Foreign bodies
      within sigmoid diverticular disease may be associated with inflammation,
      perforation, abscess and fistula. In current practice, diagnosis is often
      achieved with CT scan. Patients with colonic perforation or fistula generally
      require colonic resection. Patients with inflammation may merit conservative
      management, including colonoscopic foreign body retrieval. Chicken bones, tooth
      picks, and biliary stents have been reported in patients with inflammation,
      perforation and fistula, whereas all published patients with fish bone related
      diverticulosis complications experienced inflammation. Treatment might be best
      guided by the consequences of the foreign body rather than the nature of the
      underlying retained object. Diverticular bleeding secondary to a chicken bone was
      diagnosed at CT angiography and treated with colonoscopic snare retrieval of the
      bone and clipping of the bleeding diverticulum. The EndoRingsTM Device was
      retrieved with a colonoscopic balloon.

PMID- 29030790
TI  - Acculturation Gap Distress among Latino Youth: Prospective Links to Family
      Processes and Youth Depressive Symptoms, Alcohol Use, and Academic Performance.
AB  - Latino youth have higher rates of educational and mental health difficulties
      compared to peers from other racial/ethnic groups. To understand the factors
      related to such maladjustment, a mediational model linking youth report of parent
      youth acculturation gaps to prospective changes (from spring to fall semester) in
      youth report of academic performance, depressive symptoms and alcohol use via
      youth report of parent-youth conflict and family cohesion, was studied in a
      sample of 248 U.S.-and foreign-born Latino youth (Mage = 15.21 years; 50% female;
      67% U.S.-born). Parent-youth acculturation gaps were associated with changes in
      youth academic performance across two semesters via their negative impact on
      family functioning. For U.S.-born youth, parent-youth acculturation gaps were
      also linked to changes in alcohol use via parent-adolescent conflict. Results
      provide some support for the acculturative gap hypotheses while unique findings
      across nativity groups suggest that such individual-level characteristics may
      serve as important sources of variation for Latino youth.

PMID- 29030792
TI  - A Universal Intervention Program Increases Ethnic-Racial Identity Exploration and
      Resolution to Predict Adolescent Psychosocial Functioning One Year Later.
AB  - Ethnic-racial identity formation represents a key developmental task that is
      especially salient during adolescence and has been associated with many indices
      of positive adjustment. The Identity Project intervention, which targeted ethnic
      racial identity exploration and resolution, was designed based on the theory that
      program-induced changes in ethnic-racial identity would lead to better
      psychosocial adjustment (e.g., global identity cohesion, self-esteem, mental
      health, academic achievement). Adolescents (N =215; Mage =15.02, SD =.68; 50%
      female) participated in a small-scale randomized control trial with an attention
      control group. A cascading mediation model was tested using pre-test and three
      follow-up assessments (12, 18, and 67 weeks after baseline). The program led to
      increases in exploration, subsequent increases in resolution and, in turn, higher
      global identity cohesion, higher self-esteem, lower depressive symptoms, and
      better grades. Results support the notion that increasing adolescents' ethnic
      racial identity can promote positive psychosocial functioning among youth.

PMID- 29030793
TI  - Right-sided Bochdalek hernia in an elderly adult: a case report with a review of
      surgical management.
AB  - BACKGROUND: Bochdalek hernias are one of the most common types of diaphragmatic
      hernia, with most cases diagnosed during the neonatal period. In contrast,
      diagnosis of a Bochdalek hernia in an adult is rare and is typically observed on
      the left side of the diaphragm. Even more rare is the diagnosis of a right-sided
      Bochdalek hernia in an adult, where there is concurrent visceral malformation in
      most cases. CASE PRESENTATION: We describe a case of an 89-year-old female who
      presented with abdominal pain. An abdominal computed tomography (CT) scan showed
      decreased intravenous contrast uptake and thickening of the wall of herniated
      small intestine through the right side of the diaphragm, which led to the
      diagnosis of a strangulated diaphragmatic hernia. The patient underwent emergent
      laparotomy and required a partial resection of the necrotic ileum and a hernia
      repair with direct closure. Interestingly, in this case, organ malformation was
      not observed. The patient was discharged approximately 2 weeks after surgery
      without complication. CONCLUSIONS: Adult right-sided Bochdalek hernia with
      strangulation in the absence of hepatic atrophy is a rare entity. Considering the
      severity of this condition, accurate diagnosis and proper treatment are needed. A
      tailored operative approach is required on an individual case basis.

PMID- 29030794
TI  - VEGF-A gene polymorphisms and responses to intravitreal ranibizumab treatment in
      patients with diabetic macular edema.
AB  - PURPOSE: To investigate the association between VEGF gene polymorphisms and the
      responses to treatment with intravitreal ranibizumab (IVR) in patients with
      diabetic macular edema (DME). METHODS: This prospective study, conducted at the
      Kutahya Dumlupinar University Faculty of Medicine, included 95 patients with DME
      that were treated with IVR and 32 patients without DME despite proliferative
      diabetic retinopathy (PDR). The participants were divided into three groups: DME
      with non-proliferative diabetic retinopathy, DME with PDR, and PDR without DME;
      patients with DME who were treated with IVR were further divided into two groups
      based on their response to the treatment. Each patient was genotyped for five
      single nucleotide variations (SNVs) in VEGF-A: rs2010963, rs2146323, rs10434,
      rs833069, and rs6921438. RESULT: There was a statistically significant difference
      in allelic distribution of VEGF-A rs833069 polymorphism in relation to the
      severity of diabetic retinopathy (DRP) (p = 0.031). The allelic distribution of
      VEGF-A rs2146323 polymorphism tended to be associated with the severity of DRP (p
      = 0.069). There were no statistically significant differences in the allelic
      distribution of the studied five SNVs in DME patients regarding the patients'
      responses to IVR therapy. CONCLUSIONS: There is no association between the
      studied VEGF-A SNVs and the responses to IVR therapy in DME. However, the VEGF-A
      rs833069 gene polymorphism has a clear association with the severity of diabetic
      retinopathy.

PMID- 29030795
TI  - A virtual model to assess maximum treatable area in LASIK and feasibility of a
      temporal hinge.
AB  - PURPOSE: To generate virtual models using different hinge locations and to
      investigate the advantages of a temporal hinge to a superior in LASIK. METHODS:
      The study design was cross sectional. An image processing software was used to
      construct virtual LASIK models of 56 slit lamp photos of eyes. For a given hinge
      location and width, the largest flap diameter and maximum treatable stromal bed
      area were calculated, comparing temporal hinge to superior. RESULTS: Temporal
      hinge allowed a greater flap diameter than superior and thus a greater treatment
      zone area for a given hinge width. A temporal hinge allowed a greater hinge width
      than a superior hinge for a given treatment zone area. CONCLUSION: We provide a
      rational basis for a mechanically stable temporal hinge. Moreover, we provide a
      method to pre-operative model flap size and hinge location, using a slit lamp
      camera and an image editing software.

PMID- 29030796
TI  - Classification and characterization of acute macular neuroretinopathy with
      spectral domain optical coherence tomography.
AB  - PURPOSE: To classify and characterize AMN lesions with SD-OCT during a follow-up
      as long as 5 years. METHODS: Retrospective study of 14 patients (18 eyes) with
      special focus on SD-OCT. We measured thickness of inner nuclear layer (INL),
      outer retinal layer (ONL), and hyperreflective band at baseline and during follow
      up. AMN lesions were classified as type 1 and type 2. RESULTS: Of 14 patients
      (six males, eight females, mean age 29.7 years), three patients (four eyes) had
      type 1 and nine (12 eyes) had type 2. Two patients did not meet the criteria for
      AMN type 1 or 2 and were therefore classified as new subtype of AMN. In all
      patients, statistically significant thinning of ONL and INL was observable. Mean
      ONL of all patients was 90.2 +/- 7.81 and 72.3 +/- 15.64 MUm (p < 0.05) during
      follow-up; mean INL was 54.4 +/- 10.71 and 37.5 +/- 6.18 MUm (p < 0.05) in the
      course. In the subgroup analysis in AMN type 2, the thinning of both ONL and INL
      was also statistically significant (mean ONL: 87.4 +/- 6.02 and 71.6 +/- 12.7 MUm
      (p < 0.05); mean INL: 48.5 +/- 5.04 and 38.5 +/- 5.6 MUm (p < 0.05)) in the
      course. CONCLUSION: SD-OCT allows for classification, characterization, and
      further understanding of AMN lesions. Up to now, this is one of the largest AMN
      case series differentiating into different subtypes and following up for up to 5
      years. Furthermore, we describe a new AMN subtype characterized by initially
      clinically visible yellowish parafoveal lesions, subtle pigmentary changes at
      late stage, lack of classic dark appearance on IR reflectance, involvement of
      RPE/Bruch's complex, and disruption of ellipsoid zone and interdigitation zone.
      The patients suffered from a prolonged visual impairment and paracentral
      scotomata. We propose the term AMN type 3 or "paracentral acute outer
      maculopathy."

PMID- 29030797
TI  - Corneal endothelial changes following a single session of selective laser
      trabeculoplasty for pseudoexfoliative glaucoma.
AB  - PURPOSE: To evaluate corneal endothelial cell parameters after a single session
      of selective laser trabeculoplasty (SLT) in pseudoexfoliative glaucoma (PEG)
      patients. METHODS: Corneal endothelial cell parameters of 18 PEG patients were
      compared with 18 healthy subjects following SLT treatment. All patients underwent
      SLT treatment to 180 degrees of inferior trabecular meshwork. Corneal
      measurements were performed using specular microscopy (Noncon Robo SP8000, Konan
      Medical, Hyogo, Japan). Endothelial cell density (ECD), hexagonal cell ratio
      (HEX), coefficient of variation (CV) of the corneal endothelial cell layer and
      central corneal thickness of the patients were measured at each visit. RESULTS:
      There was a statistically significant decrease in ECD (p = 0.004) and a
      statistically significant increase in CV (p = 0.041) at superior cornea 1 week
      after SLT. They returned to pre-SLT values at 1 month. One hour post-SLT HEX of
      inferior cornea was statistically significantly reduced (p = 0.01). At central
      cornea, there was a significant increase in HEX after 1 week (p = 0.001). Post
      SLT IOP showed a significant positive correlation with CV and significant
      negative correlation with HEX at superior and inferior cornea. There was no
      correlation between total laser energy used and endothelial cell parameters.
      CONCLUSION: Effect of a single session of SLT on corneal endothelium of PEG
      patients appears to be transient, and superior cornea was more affected than
      central and inferior cornea. All parameters returned to pre-SLT values at 1 month
      after treatment.

PMID- 29030798
TI  - What does the character of medicine as a social practice imply for professional
      conscientious objection?
AB  - The dispute over professional conscientious objection presumes a picture of
      medicine as a practice governed by rules. This rule-based conception of medical
      practice is identifiable with John Rawls's conception of social practices. This
      conception does not capture the character of medical practice as experienced by
      practitioners, for whom it is a sensibility or "form of life" rather than rules.
      Moreover, the sensibility of medical practice as experienced by physicians is at
      best neutral, and at worst hostile, to the demands of those who would override
      physician conscientious objection to the provision of currently contested
      services. That being so, calls for overriding physician conscientious objection
      are much more demanding of the medical profession than they appear in light of
      Rawls's view. As such overriding may entail the forcible transformation of
      medicine's form of life, the author contends that it would be more prudent to
      provide contested services by circumventing the medical profession than by
      compelling it.

PMID- 29030799
TI  - Gastric Peroral Endoscopic Pyloromyotomy Therapy for Refractory Gastroparesis.
AB  - OPINION STATEMENT: Purpose of review Gastroparesis is a complex dysmotility
      disorder in which a number of normal gastric emptying mechanisms can be affected.
      The pylorus as an apparatus is particularly important since it stands as the last
      final gateway for gastric emptying. As such, pyloric interventions seem to be
      successful in reducing symptoms and also improving emptying of solids, an effect
      not observed with other medical interventions. Recent findings Gastric peroral
      endoscopic myotomy (G-POEM) is a novel technique which offers the promise of
      mimicking the success of a traditional surgical pyloroplasty, while embracing the
      minimally invasive paradigm of flexible endoscopic surgery. Emerging data seems
      to suggest that not only does G-POEM offer symptomatic and clinical improvement
      but also objective improvement in follow-up gastric emptying studies in as much
      as 70% of patients. Summary We believe that with proper patient selection, G-POEM
      will become a powerful tool for gastroenterologists managing this chronic
      debilitating disease.

PMID- 29030800
TI  - Endoscopic Treatment of Subepithelial Lesions of the Gastrointestinal Tract.
AB  - Purpose of Review The study aimed to discuss novel endoscopic approaches to
      resection of submucosal lesions. Recent Findings Endoscopic resection by
      excavation, full-thickness resection, and submucosal tunneling are by now well
      documented techniques for submucosal tumor resection. Combined approaches with
      laparoscopy such as several variations of laparoscopic endoscopic cooperation
      surgery (LECS) and non-exposed wall-inversion surgery (NEWS) are also possible
      now. Reports of these approaches show good results. However, lesion size is the
      main limitation to these approaches. Summary Endoscopic submucosal tumor
      resection can be effectively done endoscopically or by endoscopy combined with
      laparoscopy. These techniques allow localized resection of lesions at difficult
      locations such as in the gastroesophageal junction with limited influence on the
      normal anatomy. Variations in techniques are being practiced worldwide striving
      to achieve complete resection with minimal disturbance of function or
      contamination. The choice between approaches depends largely on the size and site
      of the lesion and expertise available.

PMID- 29030801
TI  - Deep Arm/Ear-ECG Image Learning for Highly Wearable Biometric Human
      Identification.
AB  - In this study, to advance smart health applications which have increasing
      security/privacy requirements, we propose a novel highly wearable ECG-based user
      identification system, empowered by both non-standard convenient ECG lead
      configurations and deep learning techniques. Specifically, to achieve a super
      wearability, we suggest situating all the ECG electrodes on the left upper-arm,
      or behind the ears, and successfully obtain weak but distinguishable ECG
      waveforms. Afterwards, to identify individuals from weak ECG, we further present
      a two-stage framework, including ECG imaging and deep feature
      learning/identification. In the former stage, the ECG heartbeats are projected to
      a 2D state space, to reveal heartbeats' trajectory behaviors and produce 2D
      images by a split-then-hit method. In the second stage, a convolutional neural
      network is introduced to automatically learn the intricate patterns directly from
      the ECG image representations without heavy feature engineering, and then perform
      user identification. Experimental results on two acquired datasets using our
      wearable prototype, show a promising identification rate of 98.4% (single-arm
      ECG) and 91.1% (ear-ECG), respectively. To the best of our knowledge, it is the
      first study on the feasibility of using single-arm-ECG/ear-ECG for user
      identification purpose, which is expected to contribute to pervasive ECG-based
      user identification in smart health applications.

PMID- 29030802
TI  - Treatment of gastroesophageal reflux disease using radiofrequency ablation
      (Stretta procedure): An interim analysis of a randomized trial.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is the most common chronic
      gastrointestinal disorder, affecting one third of the population worldwide.
      Recently, there has been a renewed interest in Stretta therapy in view of
      potential long-term side effects of PPIs and the durability of relief with
      fundoplication. METHOD: Prospective randomized study comparing the Stretta
      treatment with controls receiving PPIs. Patient (> 18 years, n = 20) with
      symptoms of heartburn, regurgitation, abnormal esophageal acid exposure (>= 4%),
      and endoscopically confirmed esophagitis were included into the study. The
      primary measure was improvement in quality of life (QOL) and decrease in the
      frequency and severity of GERD symptoms. RESULTS: The mean age of the patients
      was 39 (+/- 15) years and controls were 34 (+/- 11) years. Three months after
      Stretta, 80% reported improvement in QOL compared to 40% in the control group. At
      the end of 3 months, significant (p < 0.05) improvement in GERD symptom score for
      heartburn, regurgitation, chest pain, and cough compared with the control group
      was observed. After Stretta treatment, 60% of the patients were free of PPIs
      whereas there was no change in the control group. Almost 80% of the patients on
      Stretta treatment were satisfied with the treatment compared to 30% of the
      patients in the control group. CONCLUSION: Stretta was effective in the short
      term for the management of GERD.

PMID- 29030803
TI  - 1H, 13C and 15N backbone resonance assignments of the beta-lactamase BlaP from
      Bacillus licheniformis 749/C and two mutational variants.
AB  - Class A beta-lactamases have been widely used as versatile scaffolds to create
      hybrid (or chimeric) proteins for a series of applications ranging from basic
      research to medicine. We have, in particular, used the beta-lactamase BlaP from
      Bacillus licheniformis 749/C (BlaP) as a protein scaffold to create model
      polyglutamine (polyQ) proteins in order to better understand the mechanism(s) by
      which an expanded polyQ sequence triggers the formation of amyloid fibrils. The
      model chimeras were designed by inserting a polyQ sequence of various lengths at
      two different locations within BlaP (i.e. position 197 or position 216) allowing
      a detailed comparison of the effects of subtle differences in the environment of
      the polyQ sequence on its ability to trigger protein aggregation. In order to
      investigate the effects of the polyQ insertion at both positions on the
      structure, stability and dynamics of BlaP, a series of NMR experiments including
      H/D exchange are foreseen. Accordingly, as necessitated by these studies, here we
      report the NMR assignment of the wild-type BlaP (BlaP-WT) and of the two
      reference proteins, BlaP197Q0 and BlaP216Q0, wherein a Pro-Gly dipeptide has been
      introduced at position 197 and 216, respectively; this dipeptide originates from
      the addition of the Sma1 restriction site at the genetic level to allow further
      polyQ sequence insertion.

PMID- 29030804
TI  - A Multi-stage Representation of Cell Proliferation as a Markov Process.
AB  - The stochastic simulation algorithm commonly known as Gillespie's algorithm
      (originally derived for modelling well-mixed systems of chemical reactions) is
      now used ubiquitously in the modelling of biological processes in which
      stochastic effects play an important role. In well-mixed scenarios at the sub
      cellular level it is often reasonable to assume that times between successive
      reaction/interaction events are exponentially distributed and can be
      appropriately modelled as a Markov process and hence simulated by the Gillespie
      algorithm. However, Gillespie's algorithm is routinely applied to model
      biological systems for which it was never intended. In particular, processes in
      which cell proliferation is important (e.g. embryonic development, cancer
      formation) should not be simulated naively using the Gillespie algorithm since
      the history-dependent nature of the cell cycle breaks the Markov process. The
      variance in experimentally measured cell cycle times is far less than in an
      exponential cell cycle time distribution with the same mean.Here we suggest a
      method of modelling the cell cycle that restores the memoryless property to the
      system and is therefore consistent with simulation via the Gillespie algorithm.
      By breaking the cell cycle into a number of independent exponentially distributed
      stages, we can restore the Markov property at the same time as more accurately
      approximating the appropriate cell cycle time distributions. The consequences of
      our revised mathematical model are explored analytically as far as possible. We
      demonstrate the importance of employing the correct cell cycle time distribution
      by recapitulating the results from two models incorporating cellular
      proliferation (one spatial and one non-spatial) and demonstrating that changing
      the cell cycle time distribution makes quantitative and qualitative differences
      to the outcome of the models. Our adaptation will allow modellers and
      experimentalists alike to appropriately represent cellular proliferation-vital to
      the accurate modelling of many biological processes-whilst still being able to
      take advantage of the power and efficiency of the popular Gillespie algorithm.

PMID- 29030805
TI  - An Explicit Structural Model of Root Hair and Soil Interactions Parameterised by
      Synchrotron X-ray Computed Tomography.
AB  - The rhizosphere is a zone of fundamental importance for understanding the
      dynamics of nutrient acquisition by plant roots. The canonical difficulty of
      experimentally investigating the rhizosphere led long ago to the adoption of
      mathematical models, the most sophisticated of which now incorporate explicit
      representations of root hairs and rhizosphere soil. Mathematical upscaling
      regimes, such as homogenisation, offer the possibility of incorporating into
      larger-scale models the important mechanistic processes occurring at the
      rhizosphere scale. However, we lack concrete descriptions of all the features
      required to fully parameterise models at the rhizosphere scale. By combining
      synchrotron X-ray computed tomography (SRXCT) and a novel root growth assay, we
      derive a three-dimensional description of rhizosphere soil structure suitable for
      use in multi-scale modelling frameworks. We describe an approach to mitigate sub
      optimal root hair detection via structural root hair growth modelling. The growth
      model is explicitly parameterised with SRXCT data and simulates three-dimensional
      root hair ideotypes in silico, which are suitable for both ideotypic analysis and
      parameterisation of 3D geometry in mathematical models. The study considers
      different hypothetical conditions governing root hair interactions with soil
      matrices, with their respective effects on hair morphology being compared between
      idealised and image-derived soil/root geometries. The studies in idealised
      geometries suggest that packing arrangement of soil affects hair tortuosity more
      than the particle diameter. Results in field-derived soil suggest that hair
      access to poorly mobile nutrients is particularly sensitive to the physical
      interaction between the growing hairs and the phase of the soil in which soil
      water is present (i.e. the hydrated textural phase). The general trends in fluid
      coincident hair length with distance from the root, and their dependence on
      hair/soil interaction mechanisms, are conserved across Cartesian and cylindrical
      geometries.

PMID- 29030806
TI  - Palliative Care in the Management of Patients with Advanced Heart Failure.
AB  - Globally, there are 18-million individuals living with heart failure, a disease
      that is responsible for 12-15 million office visits and 6.5 million inpatient
      hospitalizations each year. As HF becomes advanced or end-stage, patients often
      live in a cycle of frequent transitions between care settings, and with unmet
      needs, including distress from inadequately managed symptoms. Prognostication in
      patients with heart failure can be challenging due to the unpredictable
      exacerbating-remitting illness trajectory that is associated with this
      progressive disease. Recurrent hospitalizations, worsening functional status and
      refractory symptoms, despite optimal therapies, are among the most salient
      predictors indicating that patients with advanced heart failure are nearing the
      end of life. Palliative care is a specialized form of medical care that has been
      shown to help improve severity of symptoms, facilitate discussions regarding
      medical decision making/advance care planning, and provide support for patients
      and their families. Palliative care can be used alongside curative treatments and
      has been shown to improve patient satisfaction and quality of life. Anorexia
      cachexia syndrome, dyspnea, fatigue, pain and depression are among the most
      common symptoms experienced by patients suffering from advanced heart failure.
      Palliative care can help alleviate these symptoms and also facilitate
      conversations about decision making surrounding resuscitation status and use or
      deactivation of medical devices, such as an implantable-cardioverter
      defibrillator (ICD). Clinical practice guidelines from the American College of
      Cardiology and American Heart Association report that aggressive life-sustaining
      treatments and therapies should not be utilized in patients with advanced heart
      failure who have refractory symptoms that are not responding to medical therapy.
      The focus of care should switch to controlling symptoms, reducing hospital
      admissions and improving health-related quality of life, which can be supported
      by the incorporation of palliative care into the treatment plan.

PMID- 29030807
TI  - Trends in Cannabis Use Disorder among Pregnant Women in the U.S., 1993-2014.

PMID- 29030808
TI  - Child Overweight and Obesity in Shanghai, China: Contextualizing Chinese
      Socioeconomic and Gender Differences.
AB  - PURPOSE: Childhood overweight and obesity is on the rise in China and in Chinese
      cities in particular. The aim of this study is to explore the extent of income
      differences in childhood overweight in Shanghai, China, and examine demographic,
      social, and behavioral explanations for these differences. METHODS: Using the
      2014 Child Well-Being Study of Shanghai, China-a survey that included extensive
      contextual information on children and their families in China's most populous
      city, prevalence rates and adjusted odds ratios of child overweight and obesity
      at age 7 were calculated by income tercile controlling for a wide variety of
      sociodemographic variables. RESULTS: District aggregate income increases the odds
      of child overweight/obesity, but only for boys. In contrast, rural hukou status
      was associated with lower odds of overweight/obesity for girls. CONCLUSIONS: Boys
      at age 7 are more likely to be overweight and obese than girls. District income
      further increases this likelihood for boys, while rural hukou status decreases
      this likelihood for girls, suggesting that preferences for boys and thinness
      ideals for girls may play a role in the income patterning of childhood overweight
      and obesity.

PMID- 29030809
TI  - Molecular Regulation of Cellular Quiescence: A Perspective from Adult Stem Cells
      and Its Niches.
AB  - Cellular quiescence is a reversible growth arrest state. In response to
      extracellular environment, quiescent cells are capable of resuming proliferation
      for tissue homeostasis and tissue regeneration. Subpopulations of adult stem
      cells remain quiescent and reside in their specialized stem cell niches. Within
      the niche, they interact with a repertoire of niche components. Niche integrates
      signals to maintain quiescence or gear stem cells toward regeneration. Recent
      studies provide insights into the regulatory components of stem cell niche and
      their influence on residing stem cells. Aberrant niche activities perturb stem
      cell quiescence and activation, compromise stem cell functions, and contribute to
      tissue aging and disease pathogenesis. This review covers current knowledge
      regarding cellular quiescence with a focus on original and emerging concepts of
      how niches influence stem cell quiescence.

PMID- 29030811
TI  - Flow Cytometric Detection of G0 in Live Cells by Hoechst 33342 and Pyronin Y
      Staining.
AB  - Hoechst 33342 and Pyronin Y double staining can be used to measure DNA and RNA
      content in live cells by flow cytometry. Quiescent cells at G0 phase have the
      same amount of DNA as cells at G1 phase but lower RNA levels compared to
      proliferating cells. Therefore, resting cells in G0 phase can be distinguished
      from proliferating cells in G1, S, and G2 M phases. This chapter describes a
      protocol for double staining of live cells with Hoechst 33342 and Pyronin Y.
      Combined with immunophenotyping of intact and live cells Hoechst 33342 and
      Pyronin Y staining is a powerful noninvasive method for the analysis and
      isolation of quiescent cells from any defined cell population.

PMID- 29030810
TI  - An In Vitro Model of Cellular Quiescence in Primary Human Dermal Fibroblasts.
AB  - Cellular quiescence is a reversible mode of cell cycle exit that allows cells and
      organisms to withstand unfavorable stress conditions. The factors that underlie
      the entry, exit, and maintenance of the quiescent state are crucial for
      understanding normal tissue development and function as well as pathological
      conditions such as chronic wound healing and cancer. In vitro models of
      quiescence have been used to understand the factors that contribute to quiescence
      under well-controlled experimental conditions. Here, we describe an in vitro
      model of quiescence that is based on neonatal human dermal fibroblasts. The
      fibroblasts are induced into quiescence by antiproliferative signals, contact
      inhibition, and serum-starvation (mitogen withdrawal). We describe the isolation
      of fibroblasts from skin, methods for inducing quiescence in isolated
      fibroblasts, and approaches to manipulate the fibroblasts in proliferating and
      quiescent states to determine critical regulators of quiescence.

PMID- 29030812
TI  - Using Carboxy Fluorescein Succinimidyl Ester (CFSE) to Identify Quiescent
      Glioblastoma Stem-Like Cells.
AB  - Tumor resistance to conventional therapies is a major challenge toward the
      eradication of cancer, a life-threatening disease. This resistance mainly results
      from tumor heterogeneity and more specifically from the existence of "stem-like"
      cells that remain in a quiescent state for long periods of time and thus escape
      commonly used anti-cancer drugs resulting in treatment failure. Therefore,
      targeting this subpopulation would present a viable strategy to overcome tumor
      burden. This daunting task requires a deep and thorough understanding of the
      biology of the quiescent stem-cell population, their interaction with tumor
      microenvironments, and mechanisms used to sustain themselves despite aggressive
      therapies. In this chapter, we describe detailed technical procedures for the
      isolation of quiescent or infrequently dividing stem-like cells in cultured
      glioblastoma tumor cells using carboxy fluorescein succinimidyl ester (CFSE)
      staining and flow cytometric analysis. Quiescent glioblastoma cells with stem
      like features are characterized and subsequently isolated based on their ability
      to retain the CFSE labeling.

PMID- 29030813
TI  - Isolation of Neural Stem and Progenitor Cells from the Adult Brain and Live
      Imaging of Their Cell Cycle with the FUCCI System.
AB  - Neural stem cells (NSCs) enter quiescence in early embryonic stages to create a
      reservoir of dormant NSCs able to enter proliferation and produce neuronal
      precursors in the adult mammalian brain. Various approaches of fluorescent
      activated cell sorting (FACS) have emerged to allow the distinction between
      quiescent NSCs (qNSCs), their activated counterpart (aNSCs), and the resulting
      progeny. In this article, we review two FACS techniques that can be used
      alternatively. We also show that their association with transgenic Fluorescence
      Ubiquitination Cell Cycle Indicator (FUCCI) mice allows an unprecedented overlook
      on the cell cycle dynamics of adult NSCs.

PMID- 29030814
TI  - Determination of Histone 2B-Green Fluorescent Protein (GFP) Retention in
      Intestinal Stem Cells.
AB  - The epithelium of the gastrointestinal tract represents the interface between the
      luminal contents of the gut and that of the host tissues and plays a central role
      not only in regulating absorption of dietary nutrients but also in providing a
      barrier to prevent the entry of bacteria and other pathogens. Repair and
      replacement of damaged aging cells within the epithelium is modulated by stem
      cells, which are located in the intestinal crypts of the small intestine.Two
      distinct populations of intestinal stem cells have been described in the
      literature, one population at the very base of the crypt and a second population
      of long-lived stem cells located just above the Paneth cell zone. Herein, we
      describe a method to label this population of long-lived GFP label retaining
      cells. This method is free from confounding factors of previous methodologies
      based on radioactive tracers and also enables functional studies not previously
      possible using the radioactive tracer techniques described in the literature.

PMID- 29030815
TI  - Detecting Hematopoietic Stem Cell Proliferation Using BrdU Incorporation.
AB  - Cellular quiescence is a key component of hematopoietic stem cell (HSC)
      homeostasis; therefore, a reliable method to measure HSC cell division is
      critical in many studies. However, measuring the proliferation rate of largely
      quiescent and rare populations of cells can be challenging. Bromo-deoxyuridine
      (BrdU) incorporation into replicating DNA is a commonly used and highly
      reproducible method to detect cell division history. Here, we describe a protocol
      for BrdU incorporation analysis in hematopoietic stem and progenitor cells that
      can provide a sensitive measure of cell division even in rare cell populations.
      In combination with flow cytometry, this method can be generalized to analyze
      other cell populations and other tissues as identified by cell surface markers.

PMID- 29030816
TI  - Cell Cycle Analysis by Mass Cytometry.
AB  - The regulated progression of cells through the cell cycle during proliferation is
      a critical factor in tumor progression, anti-neoplastic therapy response, immune
      system regulation, and developmental biology. While flow cytometric measurement
      of cell cycle progression is well established, mass cytometry assays allow the
      cell cycle to be measured along with up to 39 other antigens enabling
      characterization of the complex interactions between the cell cycle and a wide
      variety of cellular processes. This method describes the use of mass cytometry
      for the analysis of cell cycle state for cells from three different sources: in
      vitro cultured cell lines, ex vivo human blood or bone marrow, and in vivo
      labeling and ex vivo analysis of murine tissues. The method utilizes
      incorporation of 5-Iodo-2'-deoxyuridine (IdU), combined with measurement of
      phosphorylated retinoblastoma protein (pRb), cyclin B1, and phosphorylated
      histone H3 (p-HH3). These measurements can be integrated into a gating strategy
      that allows for clear separation of all five phases of the cell cycle.

PMID- 29030817
TI  - Preparation and Analysis of Saccharomyces cerevisiae Quiescent Cells.
AB  - Saccharomyces cerevisiae enter quiescence during extended growth in culture
      (greater than 7 days). Here, we describe a method to separate quiescent from non
      quiescent cells by density gradient. We also describe approaches for DAPI
      staining the chromatin of quiescent cells, measuring quiescent cell viability,
      and extracting RNA from quiescent cells for use in genomics experiments.

PMID- 29030818
TI  - Identifying Quiescent Stem Cells in Hair Follicles.
AB  - Hair follicle stem cells (HFSCs) are noted for their relative quiescence and
      therefore can be distinguished from other cells by their differential history of
      cell division. Replicating cells can be labeled by pulsing the animals repeatedly
      with 5-bromo-2'-deoxyuridine (BrdU) or tritiated thymidine ([3H]TdR), thymidine
      analogs that get incorporated into DNA during DNA synthesis. Because dividing
      cells dilute the label after each cell division, frequently dividing cells will
      lose the label over time while slow cycling cells will retain the label and thus
      are termed label retaining cells (LRCs). [3H]TdR can be visualized by
      autoradiography and BrdU can be detected by immunofluorescence with anti-BrdU
      antibodies. Alternatively, a well-established tet-regulatable transgenic mouse
      model can be used to express histone H2B-GFP in epithelial proliferative cells
      and their dilution and retention of the GFP signal can be followed. In this
      chapter, we detail the steps to perform BrdU pulse-chase and H2B-GFP pulse-chase
      experiments to identify quiescent cells in the hair follicle.

PMID- 29030819
TI  - Single EDL Myofiber Isolation for Analyses of Quiescent and Activated Muscle Stem
      Cells.
AB  - Adult satellite cells are quiescent, but are poised for activation in response to
      exercise, injury, or disease allowing adult muscle growth or repair. Once
      activated, satellite cells proliferate extensively to produce enough myogenic
      progenitors in order to regenerate the muscles. In order to self-renew, a subset
      of activated satellite cells can resist the myogenic differentiation and return
      to quiescence to replenish the satellite cell pool. These cellular processes that
      normally occur during skeletal muscle regeneration can be recapitulated ex vivo
      using isolated and cultured myofibers. Here, we describe a protocol to isolate
      single myofibers from the extensor digitorum longus muscle. Moreover, we detail
      experimental conditions for analyzing satellite cells in quiescence and
      progression through the myogenic lineage.

PMID- 29030820
TI  - Investigating Cellular Quiescence of T Lymphocytes and Antigen-Induced Exit from
      Quiescence.
AB  - Naive T cells are in a quiescent state under homeostasis but respond to antigen
      stimulation by exiting from quiescence and entering the cell cycle. Appropriate
      regulation of quiescence is crucial for maintaining T cell homeostasis at steady
      state and initiating proper T cell responses to antigen stimulation. Emerging
      evidence indicates that signaling by mechanistic target of rapamycin (mTOR) plays
      a central role in the control of T cell quiescence and antigen-induced exit from
      quiescence through coordinating immune signals, cellular metabolic programs, and
      cell cycle machinery. The mTOR-dependent regulation of quiescence has also been
      implicated in the differentiation and function of memory T cells. In this
      chapter, we describe techniques to assess quiescent state of naive T cells under
      steady state and exit from quiescence upon TCR stimulation.

PMID- 29030821
TI  - Retroviral Transduction of Quiescent Murine Hematopoietic Stem Cells.
AB  - Hematopoietic stem cells (HSCs) represent an important target cell population in
      bone marrow transplantation, cell and gene therapy applications, and the
      development of leukemia models for research. Because the hematopoietic progeny
      carries the genetic information of HSCs and replenishes the blood and immune
      system, corrective gene transfer into HSCs provides an ideal therapeutic approach
      for many monogenic hematological diseases and a useful tool for studies of HSC
      function and blood formation in normal and malignant hematopoiesis. However, the
      efficiency of gene transfer into HSCs has been limited by several features of
      viral vectors, viral titer, methods of viral transduction, and the property of
      stem cell quiescence. In this chapter, we describe the production of retrovirus
      using murine stem cell virus (MSCV)-based retroviral vectors and purification and
      transduction of murine HSCs.

PMID- 29030822
TI  - Analysis of Murine Hematopoietic Stem Cell Proliferation During Inflammation.
AB  - Normally, quiescent hematopoietic stem cells (HSC) rapidly enter the cell cycle
      following exposure to inflammatory stimuli. The analysis of HSC cell cycle
      activity in murine bone marrow during inflammation is often complicated by the
      relative rarity of HSCs and shifts in Sca-1, a key cell surface marker used to
      identify HSCs. Here, we report a method to analyze HSC proliferation and cell
      cycle distribution under inflammatory conditions. Our approach uses EdU
      incorporation and Ki67 staining coupled with DNA content quantification by DAPI.
      We also incorporate the surface marker ESAM to help minimize the potential for
      contaminating events that may confound analysis in the HSC compartment.

PMID- 29030823
TI  - A Facile, In Vitro 384-Well Plate System to Model Disseminated Tumor Cells in the
      Bone Marrow Microenvironment.
AB  - Bone marrow disseminated tumor cells (DTCs) are dormant cancer cells that harbor
      themselves in a bone marrow niche for years after patient remission before
      potentially returning to a proliferative state, causing recurrent cancer. DTCs
      reside in bone marrow environments with physiologically important mesenchymal
      stem cells that are often negatively affected by chemotherapy treatments.
      Currently, there are very few models of DTCs that recapitulate their dormant
      phenotype while producing enough samples to accurately quantify cancer and
      surrounding stromal cell behaviors. We present a three-dimensional spheroid-based
      model system that uses dual-color bioluminescence imaging to quantify
      differential cell viability in response to various compounds. We successfully
      screened for compounds that selectively eliminated cancer cells versus supportive
      stromal cells and verified results with comparison to efficacy in vivo. The
      spheroid coculture system successfully modeled key aspects of DTCs in the bone
      marrow microenvironment, facilitating testing for compounds to selectively
      eliminate DTCs.

PMID- 29030824
TI  - Distinguishing States of Arrest: Genome-Wide Descriptions of Cellular Quiescence
      Using ChIP-Seq and RNA-Seq Analysis.
AB  - Regenerative potential in adult stem cells is closely associated with the
      establishment of-and exit from-a temporary state of quiescence. Emerging evidence
      not only provides a rationale for the link between lineage determination programs
      and cell cycle regulation but also highlights the understanding of quiescence as
      an actively maintained cellular program, encompassing networks and mechanisms
      beyond mitotic inactivity or metabolic restriction. Interrogating the quiescent
      genome and transcriptome using deep-sequencing technologies offers an
      unprecedented view of the global mechanisms governing this reversibly arrested
      cellular state and its importance for cell identity. While many efforts have
      identified and isolated pure target stem cell populations from a variety of adult
      tissues, there is a growing appreciation that their isolation from the stem cell
      niche in vivo leads to activation and loss of hallmarks of quiescence. Thus, in
      vitro models that recapitulate the dynamic reversibly arrested stem cell state in
      culture and lend themselves to comparison with the activated or differentiated
      state are useful templates for genome-wide analysis of the quiescence network.In
      this chapter, we describe the methods that can be adopted for whole genome
      epigenomic and transcriptomic analysis of cells derived from one such established
      culture model where mouse myoblasts are triggered to enter or exit quiescence as
      homogeneous populations. The ability to synchronize myoblasts in G0 permits
      insights into the genome in "deep quiescence." The culture methods for generating
      large populations of quiescent myoblasts in either 2D or 3D culture formats are
      described in detail in a previous chapter in this series (Arora et al. Methods
      Mol Biol 1556:283-302, 2017). Among the attractive features of this model are
      that genes isolated from quiescent myoblasts in culture mark satellite cells in
      vivo (Sachidanandan et al., J Cell Sci 115:2701-2712, 2002) providing a
      validation of its approximation of the molecular state of true stem cells. Here,
      we provide our working protocols for ChIP-seq and RNA-seq analysis, focusing on
      those experimental elements that require standardization for optimal analysis of
      chromatin and RNA from quiescent myoblasts, and permitting useful and revealing
      comparisons with proliferating myoblasts or differentiated myotubes.

PMID- 29030825
TI  - Analysis of lncRNA-Protein Interactions by RNA-Protein Pull-Down Assays and RNA
      Immunoprecipitation (RIP).
AB  - Long noncoding RNAs (lncRNAs) have important roles in shaping chromatin by
      targeting chromatin-modifying enzymes to distinct genomic sites. This section
      covers two methods to analyze lncRNA-protein interactions. The RNA-protein pull
      down assays use either bead-bound proteins to capture in vitro transcripts, or
      immobilized synthetic RNAs to bind proteins from cell lysates. In the RNA
      immunoprecipitation (RIP) assay, endogenous RNAs are co-immunoprecipitated with a
      protein of interest. Both the methods can be applied to material from
      proliferating and quiescent cells, thus providing insights into how lncRNA
      protein interactions are altered between these two cellular states.

PMID- 29030827
TI  - Genome-Wide Identification of Transcription Factor-Binding Sites in Quiescent
      Adult Neural Stem Cells.
AB  - Transcription factors bind to specific DNA sequences and control the
      transcription rate of nearby genes in the genome. This activation or repression
      of gene expression is further potentiated by epigenetic modifications of histones
      with active and silent marks, respectively. Resident adult stem cells in the
      hematopoietic system, skin, and brain exist in a non-proliferative quiescent
      resting state. When quiescent stem cells become activated and transition to
      dividing progenitors and distinct cell types, they can replenish and repair
      tissue. Thus, determination of the position of transcription factor binding and
      histone epigenetic modification on the chromatin is an essential step toward
      understanding the gene regulation of quiescent and proliferative adult stem cells
      for potential applications in regenerative medicine. Genome-wide transcription
      factor occupancy and histone modifications on the genome can be obtained by
      assessing DNA-protein interaction through next-generation chromatin
      immunoprecipitation sequencing technology (ChIP-seq). This chapter outlines the
      protocol to perform, analyze, and validate ChIP-seq experiments that can be used
      to identify protein-DNA interactions and histone marks on the chromatin. The
      methods described here are applicable to quiescent and proliferative neural stem
      cells, and a wide range of other cellular systems.

PMID- 29030826
TI  - Analysis of MicroRNA-Mediated Translation Activation of In Vitro Transcribed
      Reporters in Quiescent Cells.
AB  - Quiescence (G0) is defined as an assortment of cell cycle arrested states that
      exhibit distinct properties. Leukemias harbor a subpopulation of G0 cells that
      can be enriched by growth factor deprivation or serum starvation. Target site
      reporters with shortened poly(A) tails show translation activation by microRNAs,
      via a noncanonical mechanism, when introduced into the nucleus of G0 cells. This
      is because recruitment by the activation causing FXR1a-microRNA-protein complex
      (FXR1a-microRNP) is nuclear and requires shortened poly(A) tails to avoid
      repressive factors and canonical translation. When introduced into the cytoplasm,
      target mRNAs and microRNAs are directed toward repression rather than translation
      activation. Leukemic cell lines are difficult to transfect but can be routinely
      nucleofected-where in vitro transcribed mRNA reporters and microRNAs are
      introduced into the nucleus of G0 leukemic cells. Nucleofection of a microRNA
      target reporter and either cognate, targeting microRNA, or control microRNA, into
      the nucleus of G0 cells, enables analysis of translation activation by microRNAs
      in G0. We discuss a modified protocol that we developed for transfection of mRNAs
      along with microRNAs to test translation regulation by microRNAs in G0 leukemic
      cells.

PMID- 29030828
TI  - Study Quiescence Heterogeneity by Coupling Single-Cell Measurements and Computer
      Modeling.
AB  - Single-cell measurements combined with mathematical modeling and computer
      simulations are powerful tools for understanding and exploring dynamical
      behaviors of gene networks and cellular functions that they control. Here, we
      describe experimental and computational methods to study cellular quiescence and
      its heterogeneity at the single-cell level.

PMID- 29030829
TI  - Review: Diagnosing Common Variable Immunodeficiency Disorder in the Era of Genome
      Sequencing.
AB  - Common variable immunodeficiency disorders (CVID) are an enigmatic group of often
      heritable conditions, which may manifest for the first time in early childhood or
      as late as the eighth decade of life. In the last 5 years, next generation
      sequencing (NGS) has revolutionised identification of genetic disorders. However,
      despite the best efforts of researchers around the globe, CVID conditions have
      been slow to yield their molecular secrets. We have previously described the many
      clinical advantages of identifying the genetic basis of primary immunodeficiency
      disorders (PIDs). In a minority of CVID patients, monogenic defects have now been
      identified. If a causative mutation is identified, these conditions are
      reclassified as CVID-like disorders. Here we discuss recent advances in the
      genetics of CVID and discuss how NGS can be optimally deployed to identify the
      causal mutations responsible for the protean clinical manifestations of these
      conditions. Diagnostic criteria such as the Ameratunga et al. criteria will
      continue to play an important role in patient management as well as case
      selection and sequencing strategy design until the genetic conundrum of CVID is
      solved.

PMID- 29030830
TI  - Function and quality of life among primary osteosarcoma survivors in Iran:
      amputation versus limb salvage.
AB  - PURPOSE: This study aimed to evaluate the psychometric properties of the European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      (EORTC QLQ-C30) in Iranian osteosarcoma patients and apply this to compare the
      functional level, quality of life, symptoms and financial burden of the patients
      who underwent amputation and limb-salvage operations. METHODS: This study was
      conducted at the main referral orthopedic centers in the southwest of Iran from
      2006 to 2016. After complete review of medical records, 48 patients were invited
      to attend the outpatient clinic and participate in the study via initial
      telephone interview. All data were entered in the Statistical Package for the
      Social Sciences version 15.0, and p values <0.05 were considered statistically
      significant. RESULTS: In total, 48 patients with extremities osteosarcoma
      completed the study. Of these, 31 had been treated with limb-salvage operation
      and 17 had undergone amputation. In functioning subscale, all the mean score of
      items, except social function, were higher in the limb salvage group than the
      amputee group. The mean scores (SD) of global health and quality of life were
      64.5(13.2) and 61.2+/- 12.4 in the limb salvage and amputee groups, respectively.
      In the financial impact subscale, the mean score (SD) in the limb salvage group
      was 68.8+/- (29.7) compared to 74.5(25.0) in the amputee group. CONCLUSION:
      Results support the responsiveness of the EORTC QLQ-C30 for Iranian osteosarcoma
      patients. Applying this questionnaire revealed similar functional outcome,
      quality of life, symptoms and financial burden between amputation and limb
      salvage groups.

PMID- 29030831
TI  - Practical Considerations for Using Online Methods to Engage Patients in Guideline
      Development.
AB  - Clinical practice guidelines (CPGs) have been widely used in healthcare policy,
      practice, and for suggesting future research. As patients increasingly become
      involved in CPG development to produce patient-centered recommendations, more
      research is needed on methods to engage patients, particularly methods allowing
      for scalable engagement of large, diverse, and geographically distributed groups
      of patients. In this article, we discuss practical considerations for using
      online methods to engage patients in CPG development. To inform this discussion,
      we conducted a rapid, systematic review of literature on patient involvement in
      CPG development and used qualitative evidence synthesis techniques to make
      inferences about potential advantages and challenges of using online methods to
      engage patients in this context. We identified 79 articles containing information
      about involving patients in CPG development. Potential advantages include the
      ability of online methods to facilitate greater openness and honesty by patients,
      as well as to reflect the diversity of patient views, which in turn further
      improve the utility of CPGs. Potential challenges of using online methods may
      include the extra skill, time, and certain types of resources that may be needed
      for patient engagement, as well as the difficulty engaging specific patient
      populations. However, these challenges are mitigated by growing calls for patient
      engagement as normative for CPG development in addition to patients' increasing
      familiarity with online technologies. These practical considerations should be
      examined empirically as guideline development groups further explore the
      appropriateness of using online methods to engage patients across different
      stages of CPG development.

PMID- 29030832
TI  - Iron's fingerprint of deposits-iron speciation as a geochemical marker.
AB  - The article describes the studies of the iron speciation (the occurrence of
      Fe(II), Fe(III), and complexed iron) in acid leachable fraction of deposits. The
      speciation of iron was diverse for deposits of different origins and was the
      specific "fingerprint"-marker of deposition processes. The higher occurrence of
      Fe(II) may be connected with decantation which has been observed for lake
      sediments, the majority of Fe(III) with upper flow regime erosion-deposition
      processes, observed for river sediment deposition during flood episodes. As
      verification for this hypothesis, the explanation for the iron speciation in the
      different river sediment samples has been used.

PMID- 29030833
TI  - Voluminous pseudotumoral mass in a pregnant woman: an extraordinary presentation
      of retroperitoneal tuberculosis.

PMID- 29030834
TI  - Prognostic impact of minimal disseminated disease and immune response to NPM-ALK
      in Japanese children with ALK-positive anaplastic large cell lymphoma.
AB  - The prognostic impact of minimal disseminated disease (MDD) and anti-anaplastic
      lymphoma kinase (ALK) antibody titer in children with ALK-positive anaplastic
      large cell lymphoma (ALCL) was reported by an Italian/German group. Here, we
      examine their prognostic value in Japanese children with ALK-positive ALCL. We
      evaluated nucleophosmin (NPM)-ALK transcripts in 60 patients at diagnosis by RT
      PCR and real-time PCR (qPCR). The antibody titer was assessed in 35 patients.
      Fifty-two percent were MDD positive by RT-PCR and 37% had more than 10 copies of
      NPM-ALK per 104 copies of ABL (10NCNs) by qPCR. Fifty-one percent of 35 patients
      had high antibody titer (> 1/750). Progression-free survival (PFS) of the
      patients with > 10 NCNs or low antibody titers was significantly poorer than that
      of patients with <= 10 NCNs or high antibody titers (> 1/750) (P = 0.016, 0.029),
      respectively, although we observed no difference in PFS associated with positive
      MDD on RT-PCR. On stratification using a combination of MDD and antibody titer,
      PFS for patients with > 10 NCNs and low antibody titer was extremely low (30.0%).
      Combined evaluation of MDD and anti-ALK antibody titer at diagnosis may thus be
      valuable for stratification of treatment for childhood ALCL.

PMID- 29030835
TI  - A new technique for tension-free reconstruction in large incisional hernia.
AB  - In the surgical management of large incisional hernias, the main target is the
      closure of the abdominal wall defect on the midline without a dangerous increase
      in the intraabdominal pressure. In this setting, new intraperitoneal prosthesis
      and components separation techniques were proposed to solve this problem. Both
      solutions present some critical issues. A new surgical approach with a free
      lateral double layer prosthesis totally in polypropylene both sides (FLaPp(r)) is
      proposed to overcome this problem. This is a retrospective cohort analysis study
      with a prospectively collected database from two different Italian hospitals.
      Twenty-nine patients operated from April 2010 to December 2015 were treated using
      the new prosthesis. Four patients developed postoperative complications: one
      (3.4%) presented wound infection, two (6.9%) experienced seroma, and one had a
      hematoma (3.4%). No deaths were recorded. At a median follow-up of 28.5 months
      (IQR 22-36), no hernia relapse occurred. The application of FLaPp(r) mesh is a
      safe and feasible option that can be employed to manage Rives repair in cases of
      abdominal wall defects with difficult closure of the posterior plan when the
      conventional prosthetic meshes could be unsuitable.

PMID- 29030836
TI  - Quantitative Perspectives on Fifty Years of the Journal of the History of
      Biology.
AB  - Journal of the History of Biology provides a fifty-year long record for examining
      the evolution of the history of biology as a scholarly discipline. In this paper,
      we present a new dataset and preliminary quantitative analysis of the thematic
      content of JHB from the perspectives of geography, organisms, and thematic
      fields. The geographic diversity of authors whose work appears in JHB has
      increased steadily since 1968, but the geographic coverage of the content of JHB
      articles remains strongly lopsided toward the United States, United Kingdom, and
      western Europe and has diversified much less dramatically over time. The
      taxonomic diversity of organisms discussed in JHB increased steadily between 1968
      and the late 1990s but declined in later years, mirroring broader patterns of
      diversification previously reported in the biomedical research literature.
      Finally, we used a combination of topic modeling and nonlinear dimensionality
      reduction techniques to develop a model of multi-article fields within JHB. We
      found evidence for directional changes in the representation of fields on
      multiple scales. The diversity of JHB with regard to the representation of
      thematic fields has increased overall, with most of that diversification
      occurring in recent years. Drawing on the dataset generated in the course of this
      analysis, as well as web services in the emerging digital history and philosophy
      of science ecosystem, we have developed an interactive web platform for exploring
      the content of JHB, and we provide a brief overview of the platform in this
      article. As a whole, the data and analyses presented here provide a starting
      place for further critical reflection on the evolution of the history of biology
      over the past half-century.

PMID- 29030837
TI  - Totally Robotic Combined Roux-en-Y Gastric Bypass and Hiatal Hernia Repair with
      Biological Mesh: Technical Points.

PMID- 29030838
TI  - Cloning and Identification of Recombinant Argonaute-Bound Small RNAs Using Next
      Generation Sequencing.
AB  - Argonaute proteins (AGOs) are loaded with small RNAs as guides to recognize
      target mRNAs. Since the target specificity heavily depends on the base
      complementarity between two strands, it is important to identify small guide and
      long target RNAs bound to AGOs. For this purpose, next-generation sequencing
      (NGS) technologies have extended our appreciation truly to the nucleotide level.
      However, the identification of RNAs via NGS from scarce RNA samples remains a
      challenge. Further, most commercial and published methods are compatible with
      either small RNAs or long RNAs, but are not equally applicable to both.
      Therefore, a single method that yields quantitative, bias-free NGS libraries to
      identify small and long RNAs from low levels of input will be of wide interest.
      Here, we introduce such a procedure that is based on several modifications of two
      published protocols and allows robust, sensitive, and reproducible cloning and
      sequencing of small amounts of RNAs of variable lengths. The method was applied
      to the identification of small RNAs bound to a purified eukaryotic AGO. Following
      ligation of a DNA adapter to RNA 3'-end, the key feature of this method is to use
      the adapter for priming reverse transcription (RT) wherein biotinylated
      deoxyribonucleotides specifically incorporated into the extended complementary
      DNA. Such RT products are enriched on streptavidin beads, circularized while
      immobilized on beads and directly used for PCR amplification. We provide a
      stepwise guide to generate RNA-Seq libraries, their purification, quantification,
      validation, and preparation for next-generation sequencing. We also provide basic
      steps in post-NGS data analyses using Galaxy, an open-source, web-based platform.

PMID- 29030839
TI  - Quantification of miRNAs Co-Immunoprecipitated with Argonaute Proteins Using SYBR
      Green-Based qRT-PCR.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that trigger post-transcriptional
      gene silencing. These RNAs need to be associated with the Argonaute proteins to
      be functional. This assembly begins with loading of a miRNA duplex, followed by
      the ejection of one of the strands (passenger). The remaining strand (guide)
      together with the Argonaute protein forms a ribonucleoprotein effector complex
      (the RNA-induced silencing complex, RISC). Mutation on the Argonaute protein, if
      affecting either step of the RISC assembly, impacts the function of miRNAs.
      Therefore, any observation of decreased miRNA level of mutants will provide
      insights into the role of those amino acid residues in the mechanical function of
      the Argonaute protein. In this chapter, we introduce a method to relatively
      quantify a specific miRNA co-immunoprecipitated with wild type and mutant
      Argonaute proteins from HEK293T cells, using Real-Time Quantitative Reverse
      Transcription Polymerase Chain Reaction (qRT-PCR). Spiking a synthetic exogenous
      miRNA as an internal control with RNA extraction prior to cDNA synthesis will
      normalize the C t values obtained from the qRT-PCR assays and enable us to
      quantify the relative level of Argonaute-bound miRNA.

PMID- 29030840
TI  - Gateway to Understanding Argonaute Loading of Single-Stranded RNAs: Preparation
      of Deep Sequencing Libraries with In Vitro Loading Samples.
AB  - Identification of sequences preferred by individual RNA-binding proteins (RBPs)
      has been accelerated by recent advances in the quantitative analysis of protein
      RNA interactions on a massive scale, and such experiments have even revealed
      hidden sequence specificity of RBPs that were assumed to be non-specific.
      Argonaute (AGO) proteins bind diverse guide small RNAs and were believed to have
      no sequence specificity besides the preference for particular bases at the 5'
      nucleotide. However, we recently showed that short single-stranded RNAs (ssRNAs)
      are loaded to AGOs in vivo and in cell extracts with detectable sequence
      preferences. To study the sequence specificity, we established a protocol for
      preparing the oligo-specific deep-sequencing library. The protocol includes in
      vitro loading assay that uses RNA oligos containing randomized nucleotides at the
      first five positions and also splinted-ligation that specifically amplifies the
      introduced oligo RNA species from a complex mixture of endogenous small RNAs and
      exogenously introduced RNA oligos. With the current sequencing depth, this
      procedure will allow quantitative profiling of interactions between the AGO and
      ~1000 ssRNA species with different sequences. The method would aid in studying
      the mechanism behind the selective loading of ssRNAs to AGOs and may potentially
      be applied to study interactions between RNA and other RNA-binding proteins.

PMID- 29030841
TI  - Dumbbell-PCR for Discriminative Quantification of a Small RNA Variant.
AB  - Cellular RNAs are often expressed as multiple isoforms of complex heterogeneity
      in both length and terminal sequences. IsomiRs, the isoforms of microRNAs, are
      such an example. Distinct quantification of each RNA variant is necessary to
      unravel the biogenesis mechanism and biological significance of heterogenetic RNA
      expression. Here we describe Dumbbell-PCR (Db-PCR), a TaqMan RT-PCR-based method
      that distinctively quantifies a specific small RNA variant with single-nucleotide
      resolution at terminal sequences. Db-PCR enables the quantitative analysis of RNA
      terminal heterogeneity without performing Next-Generation Sequencing.

PMID- 29030842
TI  - MicroRNA Detection by Whole-Mount In Situ Hybridization in C. elegans.
AB  - MicroRNAs (miRNAs) loaded on argonaute proteins guide RNA-induced silencing
      complexes to target mRNAs. An excellent method to decipher the spatiotemporal
      expression patterns of miRNAs is whole-mount in situ hybridization (WISH), which
      has been successfully used in vertebrate embryos but still remains unavailable
      for many animal species. Here, we describe a WISH method for miRNA detection in
      Caenorhabditis elegans at both embryonic and post-embryonic stages. Strategies
      devised for detection include fixation of animals with carbodiimide at a high
      temperature and subsequent partial digestion of the fixed animals with an
      extremely high concentration of proteinase. WISH signals are visualized by
      staining with a chromogenic substrate or a fluorescent dye.

PMID- 29030843
TI  - cCLIP-Seq: Retrieval of Chimeric Reads from HITS-CLIP (CLIP-Seq) Libraries.
AB  - HITS-CLIP (High-Throughput Sequencing after in vivo Crosslinking and
      Immunoprecipitation, CLIP-Seq) libraries contain fragments of the RNA sequences
      bound in vivo by an RNA binding protein (RBP). Such fragments, especially if they
      represent RNA duplexes bound in vivo by the RBP, can occasionally be ligated
      together to form chimeric CLIP tags. Chimeric CLIP tags from Argonaute CLIP
      libraries can provide the exact base pairing profiles of small RNAs with their
      target RNA sequences, thus solving a critical problem in the field of post
      transcriptional regulation. We recently reported an analysis of chimeric reads
      from the Drosophila Piwi protein Aubergine, which revealed a novel mechanism for
      mRNA entrapment within germ RNP granules. We term this novel approach chimeric
      CLIP (cCLIP) and present here the main steps that a researcher can take after the
      acquisition of the deep sequencing data, for the identification of candidate
      chimeric reads in Piwi CLIP libraries. Extending the scope beyond small-RNA
      binding proteins, we believe that cCLIP can be utilized to elucidate the in vivo
      functions of RNA-binding proteins in general, and especially those that modulate
      RNA secondary structures. We, therefore, also describe aspects of the generalized
      chimeric read identification problem, which can find use in the analysis of the
      CLIP libraries of any RNA-binding protein.

PMID- 29030844
TI  - Kinetic Analysis of Small Silencing RNA Production by Human and Drosophila Dicer
      Enzymes In Vitro.
AB  - Dicer enzymes produce small silencing RNAs such as microRNAs (miRNAs) and small
      interfering RNAs (siRNAs), which then are loaded into Argonaute proteins and act
      as sequence-specific guides. A powerful tool to understand the molecular
      mechanism of small silencing RNA production by Dicers is an in vitro RNA
      processing assay using recombinant Dicer proteins. Such biochemical analyses have
      elucidated the substrate specificities and kinetics of Dicers, the mechanism by
      which the length of small RNAs produced by Dicers is determined, and the effects
      of Dicer-partner proteins and endogenous small molecules such as ATP and
      inorganic phosphate on small RNA production by Dicers, among others. Here, we
      describe methods for in vitro small RNA production assay using recombinant human
      and Drosophila Dicer proteins.

PMID- 29030845
TI  - Nucleic Acid-Binding Assay of Argonaute Protein Using Fluorescence Polarization.
AB  - Nucleic acid binding by the Argonaute protein is an important trigger step in the
      Argonaute-dependent gene silencing system. We established an in vitro method to
      detect the nucleic acid binding activity of the Argonaute protein by fluorescence
      polarization. In this chapter, we will describe the expression and purification
      of the prokaryotic (Rhodobacter sphaeroides) Argonaute protein, and the nucleic
      acid-binding analysis using a Fluorescence Polarization System (Beacon 2000).

PMID- 29030846
TI  - Reconstitution of RNA Interference Machinery.
AB  - Small RNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs),
      silence protein expression from target mRNAs bearing their complementary
      sequences, via the formation of the effector complex called RNA-induced silencing
      complex (RISC). Although the mechanism of RISC assembly has been studied for
      nearly two decades, the detailed mechanism has still remained unclear in part due
      to the lack of a pure reconstitution system. Recently, we identified all the core
      proteins necessary for RISC assembly in flies and successfully recapitulated the
      assembly of catalytically active RISC with eight recombinant proteins. The
      reconstitution system provides a versatile framework for detailed studies of RISC
      assembly, including single molecule analysis as described in another chapter in
      this issue.

PMID- 29030847
TI  - Single-Molecule Analysis for RISC Assembly and Target Cleavage.
AB  - RNA-induced silencing complex (RISC) is a small RNA-protein complex that mediates
      silencing of complementary target RNAs. Biochemistry has been successfully used
      to characterize the molecular mechanism of RISC assembly and function for nearly
      two decades. However, further dissection of intermediate states during the
      reactions has been warranted to fill in the gaps in our understanding of RNA
      silencing mechanisms. Single-molecule analysis with total internal reflection
      fluorescence (TIRF) microscopy is a powerful imaging-based approach to
      interrogate complex formation and dynamics at the individual molecule level with
      high sensitivity. Combining this technique with our recently established in vitro
      reconstitution system of fly Ago2-RISC, we have developed a single-molecule
      observation system for RISC assembly. In this chapter, we summarize the detailed
      protocol for single-molecule analysis of chaperone-assisted assembly of fly Ago2
      RISC as well as its target cleavage reaction.

PMID- 29030848
TI  - Profiling Open Chromatin Structure in the Ovarian Somatic Cells Using ATAC-seq.
AB  - The assay for transposase-accessible chromatin using sequencing (ATAC-seq) was
      recently established as a method to profile open chromatin, which overcomes the
      sample size limitations of the alternative methods DNase/MNase-seq. To
      investigate the role of Piwi in heterochromatin formation around transposable
      element loci, we have used ATAC-seq to examine chromatin accessibility at target
      transposable elements in a Drosophila cultured cell line, ovarian somatic cells
      (OSCs). In this chapter, we describe our method to profile open chromatin
      structure in OSCs using ATAC-seq.

PMID- 29030849
TI  - Assessing miR-451 Activity and Its Role in Erythropoiesis.
AB  - The ability to microinject small RNAs and mRNAs into zebrafish embryos, of
      different genetic backgrounds, allows for the precise dissection of microRNA
      processing pathways at the molecular level, while simultaneously provides insight
      into their physiologic role. Here, we apply such an approach to determine the
      impact of Argonaute 2 in the processing of miR-451, a vertebrate-specific
      microRNA required for terminal erythrocyte differentiation. This was achieved
      using fluorescent microRNA reporter sensor assays and phenotype rescue
      experiments.

PMID- 29030850
TI  - Functional Analysis of MicroRNAs in Neurogenesis During Mouse Cortical
      Development.
AB  - The advantage of using in utero electroporation is that it can study the gene
      function during neurodevelopment in vivo. Using functional analysis of a microRNA
      (miRNA) gene as an example, this protocol describes a set of techniques that are
      crucial for the success of neurogenesis studies, including mice time mating,
      plasmid preparation, utero electroporation following miRNA injection into mice
      embryonic brain ventricle, labeling of proliferating cells with EDU
      (ethynyldeoxyuridine), cryosectioning, immunofluorescence staining, and confocal
      microscopic analysis. This chapter also provides detailed technical tips
      regarding experimental planning, mouse surgery, multi-embryo injection with
      different plasmids, electroporation, and maintenance of pregnant mother with post
      electroporated embryo.

PMID- 29030851
TI  - Cellular Approaches in Investigating Argonaute2-Dependent RNA Silencing.
AB  - In mammals, there are four Argonaute (Ago) family proteins that play crucial
      roles in RNA silencing, a process wherein microRNA (miRNA) mediates inhibition of
      target mRNA translation. Among the Ago proteins, Argonaute2 (Ago2) uniquely
      possesses an endoribonuclease (slicer) activity that is critical for the
      biogenesis of specific miRNAs and mRNA cleavage. This Ago2 slicer activity is
      required for postnatal development. Despite its important roles, there are still
      gaps in our understanding of the mechanistic basis of Ago2's unique functions in
      vivo due to a limited availability of experimental tools. In order to investigate
      Ago2's functions, we generated a new cellular model of Ago2-deficiency in 3T3
      mouse embryonic fibroblasts (MEFs). This cell line can be used for investigating
      general Ago2 functions, but also for further understanding of Ago2's unique
      characteristics including the slicer activity, specific amino acid residues, and
      domains in Ago2 by reconstitution of Ago2 mutants. Here, we describe the methods
      for establishing Ago2-deficient MEFs and for reconstituting the MEFs with an Ago2
      mutant lacking its slicer activity by means of a retrovirus-mediated gene
      transfer.

PMID- 29030852
TI  - Genomic Tagging of AGO1 Using CRISPR/Cas9-Mediated Homologous Recombination.
AB  - Tagging of genes at the endogenous loci is a powerful strategy for the analysis
      of protein function. We have developed a homologous recombination-based approach
      for inserting epitope tag into Drosophila AGO1 locus by employing the CRISPR/Cas9
      technology. The methodology involves co-expression of sgRNA (containing 20
      nucleotide AGO1 targeting sequence) and Cas9 protein, together with a donor
      template that has HA-AGO1 cassette flanked by sequences homologous to the AGO1
      locus. The integration is efficient and readily monitored by immunostaining of
      the transgenic cell line. This method facilitates rapid generation of stable cell
      lines and allows insertion of any tag sequence into endogenous loci, thus
      accelerating characterization of the tagged proteins.

PMID- 29030853
TI  - Accurate Profiling and Quantification of tRNA Fragments from RNA-Seq Data: A Vade
      Mecum for MINTmap.
AB  - There is an increasing interest within the scientific community in identifying
      tRNA-derived fragments (tRFs) and elucidating the roles they play in the cell.
      Such endeavors can be greatly facilitated by mining the numerous datasets from
      many cellular contexts that exist publicly. However, the standard mapping tools
      cannot be used for the purpose. Several factors complicate this endeavor
      including: the presence of multiple identical or nearly identical isodecoders at
      various genomic locations; the presence of identical sequence segments that are
      shared by isodecoders of the same or even different anticodons; the existence of
      numerous partial tRNA sequences across the genome; the existence of hundreds of
      "lookalike" sequences that resemble true tRNAs; and others. This is generating a
      need for specialized tools that can mine deep sequencing data to identify and
      quantify tRFs. We discuss the various complicating factors and their
      ramifications, and how to use and run MINTmap, a tool that addresses these
      considerations.

PMID- 29030854
TI  - Acute Pancreatitis Secondary to Severe Hypertriglyceridaemia in a Patient with
      Type 1a Glycogen Storage Disease: Emergent Use of Plasmapheresis.
AB  - Acute pancreatitis is a well-recognised complication of hypertriglyceridaemia.
      High serum triglycerides may develop in the autosomal recessive disorder glycogen
      storage disease (GSD). Plasmapheresis has been effective in reducing triglyceride
      levels in pancreatitis secondary to other conditions but not previously described
      in GSD. We describe a 16-year-old male with type 1a GSD who presented with severe
      abdominal pain, tachycardia and tachypnoea. Abdominal computed tomography (CT)
      demonstrated acute pancreatitis. Serum triglycerides were 91.8 mM. Despite
      intravenous fluids and morphine sulphate, he remained seriously ill, and
      plasmapheresis was therefore started. After daily plasma exchange for 6 days,
      triglyceride levels dropped to 5 mM. This was associated with a rapid resolution
      of pancreatitis. Plasmapheresis is effective in rapidly reducing
      hypertriglyceridaemia from numerous causes, including glycogen storage disease,
      and may facilitate recovery from acute pancreatitis.

PMID- 29030855
TI  - Extended Experience of Lower Dose Sapropterin in Irish Adults with Mild
      Phenylketonuria.
AB  - Adherence to dietary and treatment recommendations is a long-standing concern for
      adults and adolescents with PKU and treating clinicians. In about 20-30% of PKU
      patients, Phe levels may be controlled by tetrahydrobiopterin (BH4) therapy. The
      European PKU 2017 Guidelines recommends treatment with BH4 for cases of proven
      long-term BH4 responsiveness, with a recommended dosage of Sapropterin 10-20
      mg/kg/day.We report four young Irish patients with mild PKU, known to be BH4
      responsive, who were treated with lower doses of Sapropterin for over 7
      years.Case 1: Female, currently age 20. Genotype p. 165T/p/F39L, c.[194T>C];
      [117C>G]. Newborn Phe: 851 MUmol/L. Pre-Sapropterin Phe tolerance: 600 mg Phe/day
      to maintain Phe levels <400 MUmol/L. Commenced on Sapropterin 400 mg (6.5
      mg/kg/day) with increase in Phe tolerance to 800 mg/day.Case 2: Female, currently
      age 23. Genotype p. 165T/pF39L; c.[194T>C]; [117C>G]. Newborn Phe: 714 MUmol/L.
      Pre-Sapropterin Phe tolerance: 700 mg Phe/day. Commenced on Sapropterin 400 mg (8
      mg/kg/day) with increase in Phe tolerance to 800 mg/day.Case 3: Male, currently
      age 22. Genotype p. 165T/p.S349P; c.[194T>C][1045T>C]. Newborn Phe: 1,036
      MUmol/L. Pre-Sapropterin Phe tolerance: 600 mg Phe/day. Commenced on Sapropterin
      400 mg (5.4 mg/kg/day). Increased to 1,600 mg Phe/day.Case 4: Female, currently
      age 29. Genotype p.R408W/p/p.Y414C; c.[1222C>T], [1241A>G]. Newborn Phe: 1,600
      MUmol/L. Pre-Sapropterin tolerance: 450 mg/day. Commenced on Sapropterin 400 mg
      (5.0 mg/kg/day). Increased to 900 mg Phe/day.Almost 7 years of surveillance for
      these four patients has shown that this dose of Sapropterin (range 5-8 mg/kg day)
      was well tolerated and effective with a significant response to treatment and a
      marked improvement in quality of life at these lower Sapropterin doses.

PMID- 29030856
TI  - Mitochondrial 3-Hydroxy-3-Methylglutaryl-CoA Synthase Deficiency: Unique
      Presenting Laboratory Values and a Review of Biochemical and Clinical Features.
AB  - We report an 8-month-old infant with decreased consciousness after a febrile
      episode and reduced oral intake. He was profoundly acidotic but his lactate was
      normal. Serum triglycerides were markedly elevated and HDL cholesterol was very
      low. The urine organic acid analysis during the acute episode revealed a complex
      pattern of relative hypoketotic dicarboxylic aciduria, suggestive of a potential
      fatty acid oxidation disorder. MRI showed extensive brain abnormalities
      concerning for a primary energy deficiency. Whole exome sequencing revealed
      heterozygotic HMGCS2 variants. HMGCS2 encodes mitochondrial 3-hydroxy-3
      methylglutaryl-CoA (HMG-CoA) synthase-2 (HMGCS2), which catalyzes the
      irreversible and rate-limiting reaction of ketogenesis in the mitochondrial
      matrix. Autosomal recessive HMG-CoA synthase deficiency (HMGCS2D) is
      characterized by hypoketotic hypoglycemia, vomiting, lethargy, and hepatomegaly
      after periods of prolonged fasting or illness. A retrospective analysis of the
      urine organic acid analysis identified 4-hydrox-6-methyl-2-pyrone, a recently
      reported putative biomarker of HMGCS2D. There was also a relative elevation of
      plasma acetylcarnitine as previously reported in one case. Our patient highlights
      a unique presentation of HMGCS2D caused by novel variants in HMGCS2. This is the
      first report of HMGCS2D with a significantly elevated triglyceride level and
      decreased HDL cholesterol level at presentation. Given this, we suggest that
      HMGCS2D should be considered in the differential diagnosis when
      hypertriglyceridemia, or low HDL cholesterol levels are seen in a child who
      presents with acidosis, mild ketosis, and mental status changes after illness or
      prolonged fasting. Although HMGCS2D is a rare disorder with nonspecific symptoms,
      with the advent of next-generation sequencing, and the recognition of novel
      biochemical biomarkers, the incidence of this condition may become better
      understood.

PMID- 29030857
TI  - Funding blood safety in the 21st century.
AB  - BACKGROUND: Since 2000, there has been an historic increase in international
      development assistance, including blood safety projects. The result has been
      increased blood donations and infectious disease screening in many beneficiary
      countries. A comprehensive examination of international development assistance
      for blood safety has yet to be completed. STUDY DESIGN AND METHODS: This report
      examines publicly available information, including donor agency websites and
      databases and data from the 2008 and 2012 World Health Organization Global
      Database on Blood Safety. RESULTS: Between 2000 and 2015, from $602.4 million to
      $2.1 billion in international development assistance was allocated to blood
      safety programs worldwide, mostly as part of the global response to the human
      immunodeficiency virus/acquired immunodeficiency syndrome epidemic. The US
      President's Emergency Plan for AIDS Relief and the Global Fund to Fight AIDS,
      Tuberculosis, and Malaria were responsible for the majority of blood safety
      funding, which peaked in 2010 and declined through 2015. CONCLUSION: Between 2000
      and 2015, countries with high burdens of human immunodeficiency virus/acquired
      immunodeficiency syndrome received funding and technical assistance to improve
      national laboratories, increase blood component production, and strengthen
      clinical practice. Global trends in international development assistance at
      large, including aid for blood safety, suggest that funding will not rebound.

PMID- 29030858
TI  - Longitudinal melanonychia due to voriconazole therapy during treatment of
      chromoblastomycosis.

PMID- 29030859
TI  - Outpatient parenteral antimicrobial therapy in Enterococcus faecalis infective
      endocarditis.
AB  - WHAT IS KNOWN AND OBJECTIVE: Enterococcus faecalis is the third most common
      causal agent of infective endocarditis. Currently, the treatment recommended is a
      combination of ampicillin (2 g/4 h) plus ceftriaxone (2 g/12 h), so patients must
      remain hospitalized for almost 6 weeks to receive the treatment. They are not
      generally included in outpatient parenteral antimicrobial therapy programs
      because 2 different electronic pumps are required to administer these 2
      antibiotics. To enable the treatment of patients with E. faecalis IE at home, we
      designed a continuation combination regimen of ceftriaxone 4 g once daily in a
      short infusion plus ampicillin 2 g/4 h using a programmable pump. METHODS: We
      analyzed a cohort of patients attended in an outpatient parenteral antimicrobial
      therapy program that has been working since 2012 in 2 tertiary hospitals. We
      selected patients attended in this program for E. faecalis IE treated with a
      continuation regimen of ampicillin 12 g daily (2 g/4 h) and ceftriaxone 4 g every
      24 hours between July 2012 and March 2017. RESULTS AND DISCUSSION: Of the 720
      patients included in the outpatient parenteral antimicrobial therapy program, 42
      had infective endocarditis, and 4 (9.52%) were treated using the combination
      regimen described above. All patients were men, and all had left-sided native
      valve infective endocarditis. All 4 patients received ampicillin 2 g every 4
      hours and ceftriaxone 2 g every 12 hours in hospital, for a median duration of 25
      days (IQR 15-32). Thereafter, in the program, they received the following
      regimen: a 30-minute infusion of ceftriaxone 4 g in 250 mL of saline solution,
      followed by ampicillin 12 g daily in 500 mL of saline solution delivered by a
      pump programmed to administer 2 g every 4 hours. Patients received this treatment
      at home for a median of 22.5 days (IQR 13-32). All patients achieved clinical and
      microbiological cure with no recurrences or complications after a lengthy follow
      up period (median 365 days, IQR 221-406). No drug-related adverse events or
      problems with the pump system were reported. WHAT IS NEW AND CONCLUSIONS: Use of
      ceftriaxone 4 g in a single dose yields a mean plasma concentration of 30 MUg/mL.
      Ceftriaxone also has a high plasma protein binding capability, and once this
      binding is saturated, there is no reason to administer higher doses. Therefore,
      it seems reasonable to use a dose of 4 g of ceftriaxone once daily to have a
      synergist effect with ampicillin within the vegetation, and enable the treatment
      of patients with E. faecalis infective endocarditis at home. In conclusion, the
      administration of ampicillin (2 g/4 h) plus ceftriaxone (4 g/24 h) as a
      continuation regimen in an outpatient parenteral antimicrobial therapy program
      may be as effective and safe as the usual lengthy in-hospital regimen (ampicillin
      2 g/4 h and ceftriaxone 2 g/12 h) in patients with E. faecalis infective
      endocarditis.

PMID- 29030860
TI  - The Effects of Short-Time Temperature Abuse on the Microbial and Sensory Quality
      of Chilled Saithe (Pollachius virens) Fillets.
AB  - : Chilled fish products are highly perishable with a limited shelf life (10 to 14
      d). For this reason, the control of the cold chain for fish is essential. This
      study's objective was to investigate the effects of short-time temperature abuse
      during processing on spoilage of chilled saithe (Pollachius virens) fillets.
      Analysis of microbial growth, freshness grades, and sensory score by Quality
      Index method, as well as pH, were carried out during a 10-d storage period at 2
      +/- 2  degrees C. Before storage, the fillets were kept at 16  degrees C for 0,
      1, and 2 h. The results showed that spoilage of the fillets was accelerated with
      longer holding time at 16  degrees C. The 1- and 2-h holding before packing and
      storage caused a 22% (2 d) and 44% (4 d) loss of shelf life, respectively,
      compared to fillets that were packed immediately after processing. These findings
      indicate how bottlenecks and delays during processing may result in loss of
      microbial and sensory quality of chilled fish products. PRACTICAL APPLICATION:
      The observations show the importance of maintaining a low temperature in fish,
      even for a short period such as during processing. Any delays, such as due to
      buffering or mechanical failure, may accelerate spoilage of chilled products
      during subsequent storage. This effect is even more pronounced when products are
      packed in bulk volumes as the cooling rate is much slower than the piece-by-piece
      cooling rate.

PMID- 29030861
TI  - Dynamics of plasma cytokines in a patient with deficiency of interleukin-36
      receptor antagonist successfully treated with anakinra.

PMID- 29030862
TI  - Establishing Standards on Colors from Natural Sources.
AB  - Color additives are applied to many food, drug, and cosmetic products. With up to
      85% of consumer buying decisions potentially influenced by color, appropriate
      application of color additives and their safety is critical. Color additives are
      defined by the U.S. Federal Food, Drug, and Cosmetic Act (FD&C Act) as any dye,
      pigment, or substance that can impart color to a food, drug, or cosmetic or to
      the human body. Under current U.S. Food and Drug Administration (FDA)
      regulations, colors fall into 2 categories as those subject to an FDA
      certification process and those that are exempt from certification often referred
      to as "natural" colors by consumers because they are sourced from plants,
      minerals, and animals. Certified colors have been used for decades in food and
      beverage products, but consumer interest in natural colors is leading market
      applications. However, the popularity of natural colors has also opened a door
      for both unintentional and intentional economic adulteration. Whereas FDA
      certifications for synthetic dyes and lakes involve strict quality control,
      natural colors are not evaluated by the FDA and often lack clear definitions and
      industry accepted quality and safety specifications. A significant risk of
      adulteration of natural colors exists, ranging from simple misbranding or misuse
      of the term "natural" on a product label to potentially serious cases of
      physical, chemical, and/or microbial contamination from raw material sources,
      improper processing methods, or intentional postproduction adulteration.
      Consistent industry-wide safety standards are needed to address the
      manufacturing, processing, application, and international trade of colors from
      natural sources to ensure quality and safety throughout the supply chain.

PMID- 29030863
TI  - HOTAIR but not ANRIL long non-coding RNA contributes to the pathogenesis of
      multiple sclerosis.
AB  - Studies have revealed that dysregulation in gene expression is one of the main
      aspects of multiple sclerosis (MS) pathogenesis. Although the molecular pathways
      underlying the immunomodulatory role of vitamin D (VD) in MS is not completely
      elucidated, VD has more recently become a topic of interest in immune regulation
      and is widely administered to patients with MS as an immunomodulatory supplement.
      Long non-coding RNAs (lncRNAs) are known to play important roles in regulation of
      gene expression via different mechanisms. Given that VD-related genes are
      regulated by epigenetic mechanisms, here we aimed to evaluate the role of VD in
      combination with HOTAIR and ANRIL lncRNAs using in vivo, in vitro and in silico
      experiments in MS pathogenesis. Our data revealed that HOTAIR but not ANRIL
      lncRNA is probably involved in the pathogenesis of MS and experimental autoimmune
      encephalomyelitis through an unclear mechanism and it seems that by affecting the
      expression, inflammation and VD can influence HOTAIR-related mechanisms, which
      require further study.

PMID- 29030864
TI  - Phase IV head-to-head randomized controlled trial comparing ingenol mebutate
      0.015% gel with diclofenac sodium 3% gel for the treatment of actinic keratosis
      on the face or scalp.
AB  - BACKGROUND: Ingenol mebutate (IngMeb) and diclofenac sodium (DS) are approved
      treatments for actinic keratosis (AK). OBJECTIVES: To compare the efficacy and
      safety of IngMeb 0.015% gel with DS 3% gel (NCT02406014). METHODS: Patients with
      4-8 visible, discrete AK lesions on the face/scalp in a 25 cm2 contiguous area of
      skin were randomized 1:1 to IngMeb once-daily for three consecutive days or DS
      twice-daily for 90 days. Patients with AK lesions at Week 8 following IngMeb were
      offered a second IngMeb course. Primary end point was complete clearance of AK
      lesions (AKCLEAR 100) at end of first treatment course (Week 8, IngMeb; Week 17,
      DS). Secondary end points included AKCLEAR 100 at end of last treatment course
      and Week 17; adverse events (AEs) were assessed at these time points. Patients
      completed treatment satisfaction questionnaires for medication (TSQM; Week 17).
      RESULTS: AKCLEAR 100 at end of first treatment course was higher with IngMeb
      (34%) vs. DS (23%; P = 0.006). AKCLEAR 100 at end of last IngMeb course (53%) and
      Week 17 (45%) was higher than DS (both P < 0.001). The most frequent AE was
      application-site erythema (IngMeb 19%; DS 12%). Treatment-related AE (TRAE)
      duration was shorter with IngMeb. TRAE withdrawals were lower for IngMeb (2%) vs.
      DS (6%). TSQM scores for global satisfaction (P < 0.001) and effectiveness (P =
      0.002) were higher with IngMeb, as was dosing instruction adherence (>= 90% vs.
      70%). CONCLUSIONS: AKCLEAR 100, patient treatment satisfaction and effectiveness
      were significantly higher with IngMeb compared with DS, demonstrating superiority
      of IngMeb for AK treatment on face/scalp.

PMID- 29030866
TI  - Characterization of Sensory Differences in Mixing and Premium Rums Through the
      Use of Descriptive Sensory Analysis.
AB  - : This study identified and quantitated perceived sensory differences between 7
      premium rums and 2 mixing rums using a hybrid of the Quantitative Descriptive
      Analysis and Spectrum methods. In addition, the results of this study validated
      the previously developed rum flavor wheel created from web-based materials.
      Results showed that the use of the rum flavor wheel aided in sensory term
      generation, as 17 additional terms were generated after the wheel was provided to
      panelists. Thirty-eight sensory terms encompassing aroma, aroma-by-mouth,
      mouthfeel, taste and aftertaste modalities, were generated and evaluated by the
      panel. Of the finalized terms, only 5 did not exist previously on the rum flavor
      wheel. Twenty attributes were found to be significantly different among rums. The
      majority of rums showed similar aroma profiles with the exception of 2 rums,
      which were characterized by higher perceived intensities of brown sugar, caramel,
      vanilla, and chocolate aroma, caramel, maple, and vanilla aroma-by-mouth and
      caramel aftertaste. PRACTICAL APPLICATION: These results demonstrate the
      previously developed rum flavor wheel can be used to adequately describe the
      flavor profile of rum. Additionally, results of this study document the sensory
      differences among premium rums and may be used to correlate with analytical data
      to better understand how changes in chemical composition of the product affect
      sensory perception.

PMID- 29030865
TI  - The 22Rv1 prostate cancer cell line carries mixed genetic ancestry: Implications
      for prostate cancer health disparities research using pre-clinical models.
AB  - BACKGROUND: Understanding how biological factors contribute to prostate cancer
      (PCa) health disparities requires mechanistic functional analysis of specific
      genes or pathways in pre-clinical cellular and animal models of this malignancy.
      The 22Rv1 human prostatic carcinoma cell line was originally derived from the
      parental CWR22R cell line. Although 22Rv1 has been well characterized and used in
      numerous mechanistic studies, no racial identifier has ever been disclosed for
      this cell line. In accordance with the need for racial diversity in cancer
      biospecimens and recent guidelines by the NIH on authentication of key biological
      resources, we sought to determine the ancestry of 22RV1 and authenticate
      previously reported racial identifications for four other PCa cell lines.
      METHODS: We used 29 established Ancestry Informative Marker (AIM) single
      nucleotide polymorphisms (SNPs) to conduct DNA ancestry analysis and assign
      ancestral proportions to a panel of five PCa cell lines that included 22Rv1, PC3,
      DU145, MDA-PCa-2b, and RC-77T/E. RESULTS: We found that 22Rv1 carries mixed
      genetic ancestry. The main ancestry proportions for this cell line were 0.41 West
      African (AFR) and 0.42 European (EUR). In addition, we verified the previously
      reported racial identifications for PC3 (0.73 EUR), DU145 (0.63 EUR), MDA-PCa-2b
      (0.73 AFR), and RC-77T/E (0.74 AFR) cell lines. CONCLUSIONS: Considering the
      mortality disparities associated with PCa, which disproportionately affect
      African American men, there remains a burden on the scientific community to
      diversify the availability of biospecimens, including cell lines, for mechanistic
      studies on potential biological mediators of these disparities. This study is
      beneficial by identifying another PCa cell line that carries substantial AFR
      ancestry. This finding may also open the door to new perspectives on previously
      published studies using this cell line.

PMID- 29030868
TI  - Comment on 'A visual literacy course for dermatology trainees'.

PMID- 29030867
TI  - Do host-associated gut microbiota mediate the effect of an herbicide on disease
      risk in frogs?
AB  - Environmental stressors, such as pollutants, can increase disease risk in
      wildlife. For example, the herbicide atrazine affects host defences (e.g.
      resistance and tolerance) of the amphibian chytrid fungus Batrachochytrium
      dendrobatidis (Bd), but the mechanisms for these associations are not entirely
      clear. Given that pollutants can alter the gut microbiota of hosts, which in turn
      can affect their health and immune systems, one potential mechanism by which
      pollutants could increase infection risk is by influencing host-associated
      microbiota. Here, we test whether early-life exposure to the estimated
      environmental concentration (EEC; 200 MUg/L) of atrazine affects the gut
      bacterial composition of Cuban tree frog (Osteopilus septentrionalis) tadpoles
      and adults and whether any atrazine-induced change in community composition might
      affect host defences against Bd. We also determine whether early-life changes in
      the stress hormone corticosterone affect gut microbiota by experimentally
      inhibiting corticosterone synthesis with metyrapone. With the exception of
      changing the relative abundances of two bacterial genera in adulthood, atrazine
      did not affect gut bacterial diversity or community composition of tadpoles (in
      vivo or in vitro) or adults. Metyrapone did not significantly affect bacterial
      diversity of tadpoles, but significantly increased bacterial diversity of adults.
      Gut bacterial diversity during Bd exposure did not predict host tolerance or
      resistance to Bd intensity in tadpoles or adults. However, early-life bacterial
      diversity negatively predicted Bd intensity as adult frogs. Specifically, Bd
      intensity as adults was associated negatively with the relative abundance of
      phylum Fusobacteria in the guts of tadpoles. Our results suggest that the effect
      of atrazine on Bd infection risk is not mediated by host-associated microbiota
      because atrazine does not affect microbiota of tadpoles or adults. However, host
      associated microbes seem important in host resistance to Bd because the early
      life microbiota, during immune system development, predicted later-life infection
      risk with Bd. Overall, our study suggests that increasing gut bacterial diversity
      and relative abundances of Fusobacteria might have lasting positive effects on
      amphibian health.

PMID- 29030869
TI  - Evaluation of the predictive performance of bleeding risk scores in patients with
      non-valvular atrial fibrillation on oral anticoagulants.
AB  - WHAT IS KNOWN AND OBJECTIVE: Bleeding risk scores (BRSs) aid in the assessment of
      oral anticoagulant-related bleeding risk in patients with atrial fibrillation.
      Ideally, the applicability of a BRS needs to be assessed, prior to its routine
      use in a population other than the original derivation cohort. Therefore, we
      evaluated the performance of 6 established BRSs to predict major or clinically
      relevant bleeding (CRB) events associated with the use of oral anticoagulant
      (OAC) among Malaysian patients. METHODS: The pharmacy supply database and the
      medical records of patients with non-valvular atrial fibrillation (NVAF)
      receiving warfarin, dabigatran or rivaroxaban at two tertiary hospitals were
      reviewed. Patients who experienced an OAC-associated major or CRB event within 12
      months of follow-up, or who have received OAC therapy for at least 1 year, were
      identified. The BRSs were fitted separately into patient data. The discrimination
      and the calibration of these BRSs as well as the factors associated with bleeding
      events were then assessed. RESULTS: A total of 1017 patients with at least 1-year
      follow-up period, or those who developed a bleeding event within 1 year of OAC
      use, were recruited. Of which, 23 patients experienced a first major bleeding
      event, whereas 76 patients, a first CRB event. Multivariate logistic regression
      results show that age of 75 or older, prior bleeding and male gender are
      associated with major bleeding events. On the other hand, prior gastrointestinal
      bleeding, a haematocrit value of less than 30% and renal impairment are
      independent predictors of CRB events. All the BRSs show a satisfactory
      calibration for major and CRB events. Among these BRSs, only HEMORR2 HAGES (C
      statistic = 0.71, 95% CI 0.60-0.82, P < .001) and ATRIA score (C-statistic =
      0.70, 95% CI 0.58-0.82, P < .001) show acceptable discrimination performance for
      major bleeding events. All the 6 BRSs, however, lack acceptable predictive
      performance for CRB events. WHAT IS NEW AND CONCLUSION: To the best of our
      knowledge, this is the first evaluation study of the predictive performance of
      these 6 BRSs on clinically relevant bleeding events applied to the same cohort
      consisting of mainly Asian novel oral anticoagulant users. These BRSs show poor
      to acceptable predictive performance on OAC-induced major or CRB events. An
      improvement in the existing BRSs for OAC users is warranted.

PMID- 29030870
TI  - The competitive nature of signal transducer and activator of transcription
      complex formation drives phenotype switching of T cells.
AB  - Signal transducers and activators of transcription (STATs) are key molecular
      determinants of T-cell fate and effector function. Several inflammatory diseases
      are characterized by an altered balance of T-cell phenotypes and cytokine
      secretion. STATs, therefore, represent viable therapeutic targets in numerous
      pathologies. However, the underlying mechanisms by which the same STAT proteins
      regulate both the development of different T-cell phenotypes and their plasticity
      during changes in extracellular conditions remain unclear. In this study, we
      investigated the STAT-mediated regulation of T-cell phenotype formation and
      plasticity using mathematical modelling and experimental data for intracellular
      STAT signalling proteins. The close fit of our model predictions to the
      experimental data allows us to propose a potential mechanism for T-cell
      switching. According to this mechanism, T-cell phenotype switching is the result
      of the relative redistribution of STAT dimer complexes caused by the
      extracellular cytokine-dependent STAT competition effects. The developed model
      predicts that the balance between the intracellular STAT species defines the
      amount of the produced cytokines and thereby T-cell phenotypes. The model
      predictions are consistent with the experimentally observed interferon-gamma to
      interleukin-10 switching that regulates human T helper type 1/type 1 regulatory T
      cell responses. The proposed model is applicable to a number of STAT signalling
      circuits.

PMID- 29030871
TI  - Fetal/neonatal alloimmune thrombocytopenia due to anti-CD36 antibodies: antibody
      evaluations by CD36-transfected cell lines.
AB  - BACKGROUND: Isoantibodies against CD36 (platelet glycoprotein 4), developed in
      Type I CD36-deficient mothers are frequently reported as the cause of
      fetal/neonatal alloimmune thrombocytopenia in the Asian population. Therefore,
      further detailed characterization of anti-CD36-mediated fetal/neonatal alloimmune
      thrombocytopenia is warranted. Here, we report the characterization of a patient
      with fetal/neonatal alloimmune thrombocytopenia in a Taiwanese family caused by
      anti-CD36 isoantibodies using a novel antigen-capture method. STUDY DESIGN AND
      METHODS: Platelets and monocytes were analyzed for CD36 expression by flow
      cytometry. Sequencing analysis of the CD36 gene was performed to identify the
      mutation underlying the CD36 deficiency. Stable transfected human embryonic
      kidney HEK293 cells expressing recombinant CD36 were established. These cells
      were used for the characterization of anti-CD36 isoantibodies by flow cytometry,
      immunoprecipitation, and antigen-capture assay. RESULTS: Flow cytometry analysis
      revealed a total absence of CD36 on both platelets and monocytes of the mother
      (Type I CD36-deficient) caused by heterozygous deletions of the CD36 gene
      (332_333delCA and c.1254 + 6_1254 + 11delTATTTG). Analysis of maternal serum with
      CD36-transfected HEK293 cells by flow cytometry, immunoprecipitation, and antigen
      capture assay demonstrated the presence of anti-CD36 isoantibodies in maternal
      serum. Interestingly, this antibody could not be detected by the monoclonal
      antibody immobilization of platelet antigens assay when anti-CD36 monoclonal
      antibody (clone FA6-152) was used as the capture antibody. CONCLUSION: This case
      reemphasizes the role of anti-CD36 isoantibodies on the pathomechanism of
      fetal/neonatal alloimmune thrombocytopenia. The fact that the monoclonal antibody
      immobilization of platelet antigens assay does not seem to be reliable for the
      identification of all anti-CD36 antibodies indicates that screening of anti-CD36
      isoantibodies by a monoclonal antibody-independent method, as presented here,
      should be considered.

PMID- 29030872
TI  - Survival and detection of Bacillus cereus in the presence of Escherichia coli,
      Salmonella enteritidis, Staphylococcus aureus, Pseudomonas aeruginosa and Candida
      albicans after rechallenge in make-up removers.
AB  - OBJECTIVE: Pathogenic contamination of cosmetics intended to be applied on or
      around the eye area, including make-up removers, may lead to severe eye
      infections. To assess the efficacy of antimicrobial preservatives in these
      products, we investigated the survival and detection of Bacillus cereus F 4227A
      spiked into make-up removers, alone and in the presence of other relevant micro
      organisms. METHODS: Four brands of make-up removers, A, B, C and D, were
      challenged three times (day 0, day 7 and day 14) using B. cereus, in pure and
      mixed cultures, at a final concentration of 5 log CFU per mL of Bacillus cereus
      or 6 log CFU per mL for other micro-organisms. Inoculated samples were diluted
      and spiral-plated after 30 min and 24 h of each challenge onto selective media
      for recovery of surviving micro-organisms: BACARA (B. cereus), MacConkey (E.
      coli), ChromID (P. aeruginosa), XLT4 (S. enteritidis), Baird Parker agar (Staph.
      aureus) and PDA+chlortetracycline HCL (C. albicans). RESULTS: The population of
      B. cereus spiked as a pure culture increased significantly from the first to the
      third challenge after 30-min exposure time, going from 0.73 to 2.59 in A, from
      0.80 to 2.69 in B and from 0.80 to 1.67 log CFU per mL in C (P < 0.05). Likewise,
      the B. cereus population from the mixed cultures had a significantly higher
      survival count at the third challenge: from 0.12 log MPN per mL to 2.16 log CFU
      per mL in A, 0.57 to 2.27 log CFU per mL in B and from undetected (LOD = 0.48 log
      MPN) to 0.98 log CFU per mL in C, respectively. After challenges, Staph. aureus,
      C. albicans and P. aeruginosa increased in B; Staph. aureus and C. albicans in C;
      and E. coli and Staph. aureus in D. The growth of other bacteria types was
      unaffected by the number of challenges, but B. cereus population was detected
      with the third challenge. CONCLUSION: It is appropriate to assess the
      antimicrobial efficacy of preservatives using at least three challenges,
      especially for cosmetics that are subjected to repetitive contamination by users.

PMID- 29030873
TI  - A feasibility study for a triple-blind randomized controlled trial investigating
      the effects of oral isotretinoin on mood and quality of life in patients with
      acne vulgaris.
AB  - Isotretinoin is used in the treatment of severe acne vulgaris (AV), but has
      controversially been associated with depression and suicide. Large prospective
      studies have failed to translate this clinically. We undertook a feasibility
      study to investigate the parameters of a triple-blind, randomized controlled
      trial (RCT) assessing the effect of oral isotretinoin on quality of life (QoL)
      and mood in patients with AV. Patients meeting the inclusion criteria were
      randomized for 2 weeks to isotretinoin or doxycycline. Participants completed
      verified depression and QoL screening questionnaires at baseline and week 2. In
      total, 194 patients with AV were screened, with 48 meeting the inclusion criteria
      and 13 of these being willing to participate. The follow-up rate was 92% and
      questionnaire response rate was 96%. To our knowledge, this is the first study to
      demonstrate a successful design for a triple-blind RCT investigating the effects
      of isotretinoin on mood in patients with AV.

PMID- 29030874
TI  - Depuration of Cadmium from Blue Mussel (Mytilus edulis) by Protein Hydrolysate
      Fe2+ Complex: The Role of Metallothionein.
AB  - : Metallothionein (MT) plays a major role in the detoxification of toxic metal
      ions in mussel. This study served to investigate the effects of prepared protein
      hydrolysate-Fe2+ (PH-Fe2+ ) on depuration of cadmium salt (Cd2+ ) from blue
      mussel (Mytilus edulis). The results indicated that Cd2+ concentrations in
      control ranged from 46.1 to 47.1 MUg/g during 15 d of depuration. While, 40 mg/L
      PH-Fe2+ feed mussels exhibited obvious changes in Cd2+ concentration variables,
      which decreased by 22.8 MUg/g after 15 d of depuration, making them significantly
      lower than the values of the control. Our assumption was that Cd2+ could be
      dissociated effectively from the complex of MT-Cd2+ in mussels affected by the
      incorporation of PH-Fe2+ during the feeding period. Further results of homology
      modeling and molecular dynamics (MD) confirmed that the combined power between MT
      and Cd2+ weakened significantly by PH-Fe2+ . This condition affected the charge
      density and/or the loop flexibility of MT and decreased the interaction energy
      within MT-Cd2+ complex and resulted in the release of Cd2+ from the complex,
      thereby exhibiting excretion detoxification. Finally, by comparing the
      experimental results to MD results, significant positive correlations were
      observed between PH-Fe2+ and the depuration of Cd2+ from MT-Cd2+ complex.
      Overall, the findings of this study may help better understand the depuration
      mechanisms of Cd2+ combined with MT, and the PH-Fe2+ can be recommended as a
      depuration agent to decrease Cd2+ concentrations in mussels. PRACTICAL
      APPLICATION: Metallothionein (MT) is a low-molecular-weight protein with high
      metal-ion affinity. If the intracellular concentrations of metals are too high or
      if toxic metals are present within the cell, then the synthesis of MTs is induced
      and generated. In our previous work, it was found that the prepared hydrolysate
      metal element complex showed obvious depuration activity of heavy metals (Cd2+ )
      from blue mussel (Mytilus edulis). This study provided further the depuration
      mechanisms of Cd2+ from mussel (M. edulis), in particular to the role of MT and
      its chelate during the depuration process.

PMID- 29030875
TI  - Protection of Grain Products from Sitophilus oryzae (L.) Contamination by Anti
      Insect Pest Repellent Sachet Containing Allyl Mercaptan Microcapsule.
AB  - : The purpose of this study was to develop an anti-insect pest repellent sachet
      to prevent Sitophilus oryzae (L.) (Coleoptera: Curculionidae) contamination in
      grain packaging. The anti-insect pest activities of essential oils (EOs) from
      garlic (Allium Sativum), ginger (Zingiber Officinalis), black pepper (Piper
      nigrum), onion (Allium cepa), and fennel (Foeniculum vulgare) as well as major
      compounds (allyl disulfide, AD; allyl mercaptan, AM) isolated from of garlic and
      onion (AD and AM) were measured against S. oryzae. The results revealed that
      garlic EO, onion EO, AD, and AM showed strong fumigant insecticidal activities.
      Among these, AM showed the highest acetylcholinesterase (AChE) inhibition rate,
      indicating that the fumigation insecticidal efficacy of AM is related with its
      AChE inhibition ability. Subsequently, the microcapsules were produced with a
      high efficiency (80.02%) by using AM as a core material and rice flour as a wall
      material. Finally, sachet composed of rice flour microcapsule containing 2% AM
      (RAM) was produced. Repellent assay was performed to measure anti-insect pest
      ability of the RAM sachet, showed remarkable repelling effect within 48 h both in
      the presence or absence of attractant. In a release profile of RAM sachet, it was
      expected to last over 20 mo during the distribution period of brown rice.
      Moreover, RAM sachet showed no undesirable changes to the sensory properties of
      the rice both before and after cooking. Taken together, these results suggest
      that the newly developed RAM sachet could be used as a packaging material to
      protect grain products from S. oryzae contamination. PRACTICAL APPLICATION: The
      rice weevil, Sitophilus oryzae (L.) (Coleoptera: Curculionidae), causes damages
      to stored products and its contamination in grain products has become a major
      problem in cereal market. To preserve brown rice, an anti-insect pest repellent
      sachet containing 2% allyl mercaptan was newly developed and it showed remarkable
      repellent abilities against S. oryzae. It could be used as an active food
      packaging system to protect grain products from insect pest contamination.

PMID- 29030876
TI  - Reproducibility of CMRO2 determination using dynamic 17 O MRI.
AB  - PURPOSE: To assess the reproducibility of 17 O MRI-based determination of the
      cerebral metabolic rate of oxygen consumption (CMRO2 ) in healthy volunteers. To
      assess the influence of image acquisition and reconstruction parameters on
      dynamic quantification of functional parameters such as CMRO2 . METHODS: Dynamic
      17 O MRI data were simulated and used to investigate influences of temporal
      resolution (Deltat) and partial volume correction (PVC) on the determination of
      CMRO2 . Three healthy volunteers were examined in two separate examinations. In
      vivo 17 O MRI measurements were conducted with a nominal spatial resolution of
      (7.5 mm)3 using a density-adapted radial sequence with golden angle acquisition
      scheme. In each measurement, 4.0 +/- 0.1 L of 70%-enriched 17 O gas were
      administered using a rebreathing system. Data were corrected with a PVC
      algorithm, and CMRO2 was determined in gray matter (GM) and white matter (WM)
      compartments using a three-phase metabolic model (baseline, 17 O inhalation,
      decay phase). RESULTS: Comparison with the ground truth of simulations revealed
      improved CMRO2 determination after application of PVC and with Deltat <= 2:00
      min. Evaluation of in vivo data yields to CMRO2,GM  = 2.31 +/- 0.1 MUmol/g/min
      and to CMRO2,WM  = 0.69 +/- 0.04 MUmol/g/min with coefficients of variation (CoV)
      of 0.3-5.5% and 4.3-5.0% for intra-volunteer and inter-volunteer data,
      respectively. CONCLUSION: This in vivo 17 O inhalation study demonstrated that
      the proposed experimental setup enables reproducible determination of CMRO2 in
      healthy volunteers. Magn Reson Med 79:2923-2934, 2018. (c) 2017 International
      Society for Magnetic Resonance in Medicine.

PMID- 29030877
TI  - Candida albicans possess a highly versatile and dynamic high-affinity iron
      transport system important for its commensal-pathogenic lifestyle.
AB  - Iron is an essential nutrient for nearly all organisms, but iron overdose is
      toxic. The human commensal-pathogenic fungus Candida albicans traverses host
      niches with markedly different iron availability. During systemic infection, C.
      albicans must activate the high-affinity iron permease Ftr1 to acquire iron
      sequestered by the host's iron-withholding defense and suppresses iron uptake
      while residing in the iron-rich gut to avoid toxicity. Ftr1 associates with a
      ferroxidase to form an iron transporter. C. albicans contains four permeases and
      five ferroxidase homologs, suggesting 20 possible subunit combinations. Here, we
      investigated the iron-dependent expression, cellular localization and interacting
      partners of all permeases and ferroxidases and the significance of each subunit
      for gastrointestinal colonization and systemic infection in mice. We uncovered
      three distinct patterns of iron-dependent expression and highly flexible
      ferroxidase-permease partnerships, which underlie a dynamic iron transport system
      that can be deftly tuned according to iron availability. We found functional
      differentiation as well as redundancy among the ferroxidases and permeases during
      both gastrointestinal colonization and bloodstream infection. We propose that C.
      albicans possesses a sophisticated iron acquisition and utilization system
      befitting its commensal-pathogenic lifestyle. Our findings reveal new
      possibilities for medical intervention of C. albicans infection.

PMID- 29030878
TI  - The Association Between PTSD and Functional Outcome Is Mediated by Perception of
      Cognitive Problems Rather Than Objective Neuropsychological Test Performance.
AB  - Posttraumatic stress disorder (PTSD) has been consistently linked to poorer
      functional outcomes, including quality of life, health problems, and social and
      occupational functioning. Less is known about the potential mechanisms by which
      PTSD leads to poorer functional outcomes. We hypothesized that neurocognitive
      functioning and perception of cognitive problems would both mediate the
      relationship between PTSD diagnosis and functioning. In a sample of 140 veterans
      of the recent wars and conflicts in Iraq and Afghanistan, we assessed PTSD
      symptoms, history of traumatic brain injury (TBI), depression, self-report
      measures of quality of life, social and occupational functioning, and
      reintegration to civilian life, as well as perception of cognitive problems.
      Veterans also completed a comprehensive neuropsychological battery of tests.
      Structural equation modeling revealed that perception of cognitive problems, but
      not objective neuropsychological performance, mediated the relationship between
      PTSD diagnosis and functional outcomes after controlling for TBI, depression,
      education, and a premorbid IQ estimate, b = -6.29, 95% bias-corrected
      bootstrapped confidence interval [-11.03, -2.88], showing a large effect size.
      These results highlight the importance of addressing appraisals of posttrauma
      cognitive functioning in treatment as a means of improving functional outcomes.

PMID- 29030879
TI  - Environmental and genetic regulation of white-opaque switching in Candida
      tropicalis.
AB  - Phenotypic switching is a strategy by which microbial organisms adapt to
      environmental changes. The human fungal pathogens, Candida albicans and Candida
      tropicalis, are closely related species and capable of undergoing morphological
      transitions. C. albicans primarily exists in human or warm-blooded animals as a
      commensal, whereas C. tropicalis not only exists as a commensal but also is
      widely distributed in the environment. In this study, we describe the
      environmental and genetic regulatory mechanisms of white-opaque switching in C.
      tropicalis, which is associated with virulence and sexual mating. A comparative
      study with C. albicans demonstrated that C. tropicalis responds to environmental
      stimuli, such as elevated CO2 levels and pH changes, in opposite manners. An
      acidic pH and elevated CO2 levels promote the opaque phenotype in C. albicans but
      have an opposite effect in C. tropicalis, whereas alkaline pH conditions
      facilitate white-to-opaque switching and sexual mating in C. tropicalis. The
      conserved Rim101-mediated pH sensing and Ras1-cAMP/PKA signaling pathways are
      involved in this regulation. By screening an overexpression library of
      transcription factors, we identified 26 white-opaque regulators, including WOR1,
      AHR1, EFG1, CUP9, BCR1 and SFL2. Transcriptional analysis indicated that the pH
      sensing and Ras1-cAMP/PKA signaling pathways and transcriptional regulators
      coordinately regulate white-to-opaque switching.

PMID- 29030881
TI  - Effects of dietary Greek oregano (Origanum vulgare ssp. hirtum) supplementation
      on rumen fermentation, enzyme profile and microbial communities in goats.
AB  - This study was conducted to examine in vivo long-term effects of dietary dried
      oregano (Origanum vulgare ssp. hirtum) whole plant on rumen fermentation, enzyme
      profile and microbial communities. For this purpose, eight healthy, adult, non
      lactating Alpine goats were kept in tie stalls equipped for individual feeding
      and randomly divided into two homogeneous groups: one fed 0.6 kg of a concentrate
      mixture and 0.6 kg of wheat straw without any supplementation and served as
      control group (CON) while the other group (OR) fed the same diet of CON but
      supplemented with 20 g of dried oregano plants (OPs) to provide daily dosage of 1
      ml of essential oil (EO) per animal. The experimental period lasted 69 days and
      individual rumen fluid samples were obtained every 2 weeks at 0 and 4 hr after
      feeding. The results showed that dietary supplementation with OPs increased the
      protease activity (p < .001) and ammonia concentration (p < .05) in the rumen.
      Among the studied microbial populations, Peptostreptococcus anaerobius (p = .028)
      and Clostridium sticklandii (p < .001) were found to be the most sensitive to
      oregano at the current dosage. Furthermore, the total methanogen population
      significantly decreased (p < .05). It is concluded that a long-term dietary
      administration of OPs can suppress specific rumen micro-organisms and modify
      rumen fermentation favourably at least by means of suppressing methanogens.

PMID- 29030880
TI  - Direct saturation-corrected chemical exchange saturation transfer MRI of glioma:
      Simplified decoupling of amide proton transfer and nuclear overhauser effect
      contrasts.
AB  - PURPOSE: Chemical exchange saturation transfer (CEST) MRI has shown promise in
      tissue characterization in diseases like stroke and tumor. However, in vivo CEST
      imaging such as amide proton transfer (APT) MRI is challenging because of
      concomitant factors such as direct water saturation, macromolecular magnetization
      transfer, and nuclear overhauser effect (NOE), which lead to a complex contrast
      in the commonly used asymmetry analysis (MTRasym). Here, we propose a direct
      saturation-corrected CEST (DISC-CEST) analysis for simplified decoupling and
      quantification of in vivo CEST effects. METHODS: CEST MRI and relaxation
      measurements were carried out on a classical 2-pool creatine-gel CEST phantom and
      normal rat brains (N = 6) and a rat model of glioma (N = 8) at 4.7T. The proposed
      DISC-CEST quantification was carried out and compared with conventional MTRasym
      and the original three-offset method. RESULTS: We demonstrated that the DISC-CEST
      contrast in the phantom had much stronger correlation with MTRasym than the three
      offset method, which showed substantial underestimation. In normal rat brains,
      the DISC-CEST approach revealed significantly stronger APT effect in gray matter
      and higher NOE effect in white matter. Furthermore, the APT and NOE maps derived
      from DISC-CEST showed significantly higher APT effect in the tumors than
      contralateral normal tissue but no apparent difference in NOE. CONCLUSION: The
      proposed DISC-CEST method, by correction of nonlinear direct water saturation
      effect, serves as a promising alternative to both the commonly used MTRasym and
      the simplistic three-offset analyses. It provides simple yet reliable in vivo
      CEST quantification such as APT and NOE mapping in brain tumor, which is
      promising for clinical translation. Magn Reson Med 78:2307-2314, 2017. (c) 2017
      International Society for Magnetic Resonance in Medicine.

PMID- 29030882
TI  - Accelerated multicontrast volumetric imaging with isotropic resolution for
      improved peri-infarct characterization using parallel imaging, low-rank and
      spatially varying edge-preserving sparse modeling.
AB  - PURPOSE: To achieve consistent effectiveness in reconstruction of fine image
      features for cases of varying contrast-to-noise ratio (CNR) to facilitate
      translating accelerated multicontrast volumetric imaging with isotropic
      resolution toward clinical utility in peri-infarct characterization. THEORY AND
      METHODS: A low-rank and spatially varying edge-preserving constrained compressed
      sensing parallel imaging reconstruction method (CP-LASER) is developed to
      effectively preserve contrast of small-scale structures for highly accelerated
      multicontrast volumetric imaging in CNR-limited scenarios. CP-LASER
      synergistically integrates parallel imaging, low-rank and spatially varying edge
      preserving sparse modeling to achieve high signal-to-noise-ratio efficiency by
      leveraging prior knowledge about signal properties including coil sensitivity
      weighting, spatiotemporally correlated signal relaxation, and spatially varying
      sparsity. RESULTS: In the preclinical study using highly accelerated
      multicontrast volumetric imaging with an isotropic 1.5-mm resolution, CP-LASER
      demonstrated robust multicontrast reconstruction of peri-infarct characteristics
      with excellent correspondence with histopathology. CP-LASER provides better
      delineation of the peri-infarct border zone with improved sharpness than
      alternative methods in a clinical demonstration on 1.5T with an isotropic 2.2-mm
      resolution achieved in a single breath-hold. CONCLUSION: Accelerated
      multicontrast volumetric imaging with isotropic resolution using CP-LASER has
      demonstrated the potential to improve peri-infarct characterization in a clinical
      setting. Magn Reson Med 79:3018-3031, 2018. (c) 2017 International Society for
      Magnetic Resonance in Medicine.

PMID- 29030883
TI  - Polyunsaturated fatty acids influence inflammatory markers in a cellular model
      for canine osteoarthritis.
AB  - Although it is well recognized that dietary supplementation with fish oil
      improves clinical symptoms in dogs suffering from osteoarthritis, the molecular
      basis for the dietary benefit is not yet completely resolved in dogs. This study
      was designed to further clarify how polyunsaturated fatty acids (PUFA) affect key
      factors of cartilage degeneration in a canine cell culture system mimicking
      osteoarthritis. Canine chondrocytes were incubated either without or with 10 MUm
      of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA)
      or 3.6 MUm ibuprofen (Ibu) as positive control for 6 days. After the
      supplementation, cells were stimulated with 10 ng/ml interleukin-1beta (IL-1beta)
      for another 48 hr to induce osteoarthritic changes, or left unstimulated. We
      analysed fatty acid uptake via gas-liquid chromatography, nitric oxide (NO)
      production via Griess assay, prostaglandin E (PGE) production via ELISA and
      relative gene expression of several cartilage matrix proteinases, inducible
      nitric oxide synthase (iNOS) and cyclooxygenase-2 via RT-qPCR. After
      supplementation, the chondrocytes rapidly incorporated the PUFA into their fatty
      acid pools. The stimulation with IL-1beta caused a marked increase of most of the
      inflammatory markers measured. N-3 PUFA EPA reduced IL-induced gene expression of
      iNOS and corresponding production of NO. N-6 PUFA AA also decreased iNOS and NO,
      but furthermore lowered gene expression of matrix metalloproteinase-3. On the
      other hand, AA upregulated the aggrecanase ADAMTS-5 and augmented the release of
      PGE. The effect of n-3 PUFA DHA turned out to be negligible. Our results reveal
      molecular mechanisms by which PUFA affect degenerative joint disease in dogs. Of
      particular importance is that not only EPA but also AA decreased several
      inflammatory markers in our model. Thus, we conclude that an appropriate balance
      of both n-3 and n-6 fatty acids deserves more attention in dietary interventions.

PMID- 29030884
TI  - How does dietary particle size affect carnivore gastrointestinal transit: A dog
      model.
AB  - The effect of dietary particle size on gastrointestinal transit in carnivores has
      not been studied and might offer more insight into their digestive physiology.
      This study evaluated the effect of two dietary particle sizes (fine = 7.8 mm vs.
      coarse = 13 mm) of chunked day-old chicks on transit parameters in dogs. Six
      beagle dogs were fed both dietary treatments in a crossover design of 7 days with
      transit testing on the fifth day. Transit parameters were assessed using two
      markers, that is a wireless motility capsule (IntelliCap(r) ) and titanium oxide
      (TiO2 ). Dietary particle size did not affect gastric emptying time (GRT), small
      bowel transit time (SBTT), colonic transit time (CTT) and total transit time
      (aTTT) of the capsule (p > .05). There was no effect of dietary particle size on
      TiO2 mean retention time (MRT) (p > .05). The time of last TiO2 excretion (MaxRT)
      differed (p = .013) between diets, being later for the coarse diet. Both MRT (R =
      0.617, p = .032) and MaxRT (R = 0.814; p = .001) were positively correlated to
      aTTT. The ratio MRT/aTTT tended towards a difference between diets (p = .059)
      with the coarse diet exceeding fine diet values. Results show that the difference
      between capsule measurements and TiO2 is larger for the fine than the coarse diet
      suggesting that the capsule becomes more accurate when dietary particle size
      approaches marker size. Dietary particle size might have affected transit
      parameters but differences are too small to claim major physiological
      consequences.

PMID- 29030885
TI  - Phylogenetic distribution of a male pheromone that may exploit a nonsexual
      preference in lampreys.
AB  - Pheromones are among the most important sexual signals used by organisms
      throughout the animal kingdom. However, few are identified in vertebrates,
      leaving the evolutionary mechanisms underlying vertebrate pheromones poorly
      understood. Pre-existing biases in receivers' perceptual systems shape visual and
      auditory signalling systems, but studies on how receiver biases influence the
      evolution of pheromone communication remain sparse. The lamprey Petromyzon
      marinus uses a relatively well-understood suite of pheromones and offers a unique
      opportunity to study the evolution of vertebrate pheromone communication.
      Previous studies indicate that male signalling with the mating pheromone 3-keto
      petromyzonol sulphate (3kPZS) may exploit a nonsexual attraction to juvenile
      released 3kPZS that guides migration into productive rearing habitat. Here, we
      infer the distribution of male signalling with 3kPZS using a phylogenetic
      comparison comprising six of 10 genera and two of three families. Our results
      indicate that only P. marinus and Ichthyomyzon castaneus release 3kPZS at high
      rates. Olfactory and behavioural assays with P. marinus, I. castaneus and a
      subset of three other species that do not use 3kPZS as a sexual signal indicate
      that male signalling might have driven the evolution of female adaptations to
      detect 3kPZS with specific olfactory mechanisms and respond to 3kPZS with
      targeted attraction relevant during mate search. We postulate that 3kPZS
      communication evolved independently in I. castaneus and P. marinus, but cannot
      eliminate the alternative that other species lost 3kPZS communication.
      Regardless, our results represent a rare macroevolutionary investigation of a
      vertebrate pheromone and provide insight into the evolutionary mechanisms
      underlying pheromone communication.

PMID- 29030888
TI  - The emperor redressed: treating osteoporosis to prevent hip fractures in the
      oldest old.

PMID- 29030887
TI  - The impact of direct-fed microbials and enzymes on the health and performance of
      dairy cows with emphasis on colostrum quality and serum immunoglobulin
      concentrations in calves.
AB  - Thirty-six cows were blocked by calving date and randomly assigned to one of
      three treatments. Cows were on treatments 3 weeks prepartum through 8 weeks post
      partum. Treatments were as follows: (i) no direct-fed microbial (DFM) or
      cellulase and amylase enzymes (C), (ii) 45.4 g/day of DFM (D) or (iii) 45.4 g/day
      of DFM and 18.2 g/day of enzyme (DE). Total mixed ration fed and refused were
      measured daily to determine dry matter intake (DMI). Blood samples were taken
      three times weekly and analysed for beta-hydroxybutyrate, glucose and non
      esterified fatty acids. Body weight (BW) was measured weekly. Colostrum was
      weighed and analysed for IgA and IgG concentration. Calves were fed 4 L of
      colostrum within 2 hr of birth. Calf blood samples were taken at 0 and 24 hr for
      analysis of IgA and IgG concentrations and apparent efficiency of absorption.
      Milk yield was measured daily and samples collected weekly. Initial BW was
      different among treatments with D being lesser than C or DE treatments. Body
      weight, weight gain, efficiency of gain, DMI and blood parameters were
      unaffected. Treatment did not affect colostrum yield. Ash percentage of colostrum
      tended to increase with D and DE, while IgA and total solids yield decreased with
      D. Colostrum fat yield was decreased in D and DE. Treatments did not impact BW,
      serum IgA and IgG concentrations or apparent efficiency of absorption of calves.
      Post-partum BW, DMI, blood parameters, milk production and composition were
      unaffected by treatment. However, cows on D gained more BW and tended to have
      greater efficiency of gain compared to those on DE, but were similar to C.
      Somatic cell scores were greatest for D. Results indicate that DFM and enzyme
      supplementation did not improve health and performance of dairy cattle during the
      pre- and post-partum periods under conditions of this study.

PMID- 29030889
TI  - Activating Inert Alkali-Metal Ions by Electron Transfer from Manganese Oxide for
      Formaldehyde Abatement.
AB  - Alkali-metal ions often act as promoters rather than active components due to
      their stable outermost electronic configurations and their inert properties in
      heterogeneous catalysis. Herein, inert alkali-metal ions, such as K+ and Rb+ ,
      are activated by electron transfer from a Hollandite-type manganese oxide (HMO)
      support for HCHO oxidation. Results from synchrotron X-ray diffraction,
      absorption, and photoelectron spectroscopies demonstrate that the electronic
      density of states of single alkali-metal adatoms is much higher than that of K+
      or Rb+ , because electrons transfer from manganese to the alkali-metal adatoms
      through bridging lattice oxygen atoms. Electron transfer originates from the
      interactions of alkali metal d-sp frontier orbitals with lattice oxygen sp3
      orbitals occupied by lone-pair electrons. Reaction kinetics data of HCHO
      oxidation reveal that the high electronic density of states of single alkali
      metal adatoms is favorable for the activation of molecular oxygen. Mn L3 -edge
      and O K-edge soft-X-ray absorption spectra demonstrate that lattice oxygen
      partially gains electrons from the Mn eg orbitals, which leads to the upshift in
      energy of lattice oxygen orbitals. Therefore, the facile activation of molecular
      oxygen by the electron-abundant alkali-metal adatoms and active lattice oxygen
      are responsible for the high catalytic activity in complete oxidation of HCHO.
      This work could assist the design of efficient and cheap catalysts by tuning the
      electronic states of active components.

PMID- 29030886
TI  - Genetics of acute rejection after kidney transplantation.
AB  - Treatment of acute rejection (AR) following kidney transplantation has improved
      in recent years, but there are still limitations to successful outcomes. This
      review article covers literature in regard to recipient and donor genetics of AR
      kidney and secondarily of liver allografts. Many candidate gene and some genome
      wide association studies (GWASs) have been conducted for AR in kidney
      transplantation. Genetic associations with AR in kidney and liver are mostly
      weak, and in most cases, the associations have not been reproducible. A
      limitation in the study of AR is the lack of sufficiently large populations that
      account for population stratification to study the AR phenotype which in this era
      occurs in <10% of transplants. Furthermore, the AR phenotype has been difficult
      to define and the definitions of classifications have evolved over time.
      Literature related to the pharmacogenomics of tacrolimus is robust and has been
      validated in many studies. Associations between gene expression and AR are
      emerging as markers of outcomes and AR classification. In the future,
      combinations of pretransplant genotype for AR risk prediction, genotype-based
      immune suppressant dosing, and pharmacogenomic markers to select AR maintenance
      or treatment and expression markers from biopsies may provide valuable clinical
      tools for guiding treatment.

PMID- 29030890
TI  - Influences of different dietary contents of macrominerals on the availability of
      trace elements in horses.
AB  - In this study, influences of a reduced macromineral intake on the trace element
      metabolism in horses at maintenance were investigated. Background of this study
      is the revised recommendation on the macromineral supply for horses (GfE ).
      Balance studies on three adult pony geldings with body weights of 405 / 348 / 384
      kg were performed to obtain data on apparent digestibility (aD), retention and
      serum concentrations of different trace elements (Cu, Zn, Se) at different
      dietary macromineral levels. A mineral supplement or a complementary feed-with a
      reduced macromineral content-was added to a hay-based diet (daily 5.5 kg hay per
      animal, split in three servings a day), beside distilled water was offered. The
      diets were offered one after the other in a way that all ponies had the same
      sequence of treatments. The native macromineral contents of the daily offered
      amount of hay already surpassed the new recommendations whereas dietary trace
      elements needed to be supplemented. There were no statistically significant
      differences (p <= .05) concerning the aD of copper, zinc and selenium comparing
      the diets with and without macromineral supplementation. Serum levels of these
      three trace elements were not affected by the different macromineral content of
      the diet. Results of this study, based on a 22-day feeding period for each
      treatment, indicate that a macromineral supplementation of a hay-based diet for
      adult horses at maintenance was not necessary. However, no negative effects of
      added macrominerals on the trace element metabolism occurred in this study.

PMID- 29030891
TI  - Seasonal below-ground metabolism in switchgrass.
AB  - Switchgrass (Panicum virgatum), a perennial, polyploid, C4 warm-season grass is
      among the foremost herbaceous species being advanced as a source of biomass for
      biofuel end uses. At the end of every growing season, the aerial tissues senesce,
      and the below-ground rhizomes become dormant. Future growth is dependent on the
      successful over-wintering of the rhizomes. Although the importance of rhizome
      health to overall year-upon-year plant productivity has been long recognized,
      there is limited information on seasonal changes occurring during dormancy at
      both the transcriptome and metabolite levels. Here, global changes in
      transcriptomes and metabolites were investigated over two growing seasons in
      rhizomes harvested from field-grown plants. The objectives were: (a) synthesize
      information on cellular processes that lead to dormancy; and (b) provide models
      that could account for major metabolic pathways present in dormant switchgrass
      rhizomes. Overall, metabolism during dormancy appeared to involve discrete but
      interrelated events. One was a response to abscisic acid that resulted in
      dehydration, increases in osmolytes and upregulation of autophagic processes,
      likely through the target of rapamycin complex and sucrose non-fermentative
      related kinase-based signaling cascades. Another was a recalibration of energy
      transduction through apparent reductions in mitochondrial oxidative
      phosphorylation, increases in substrate level generation of ATP and reducing
      equivalents, and recycling of N and possibly CO2 through refixation. Lastly,
      transcript abundances indicated that cold-related signaling was also occurring.
      Altogether, these data provide a detailed overview of rhizome metabolism,
      especially during dormancy, which can be exploited in the future to improve
      winter survival in switchgrass.

PMID- 29030892
TI  - Radical Behavior of CO2 versus its Deoxygenation Promoted by Vanadium Aryloxide
      Complexes: How the Geometry of Intermediate CO2 -Adducts Determines the
      Reactivity.
AB  - The reactivity of carbon dioxide with vanadium(III) aryloxo complexes has been
      investigated. The formation of either carbon monoxide or incorporation into the
      ligand system with the ultimate formation of organic ester was observed depending
      on the overall electron donor ability of the ligand field. DFT calculations were
      carried out to investigate the proposed mechanism for carbon dioxide coordination
      and reduction.

PMID- 29030895
TI  - Antagonistic pleiotropy can maintain fitness variation in annual plants.
AB  - Antagonistic pleiotropy (AP) is a genetic trade-off between different fitness
      components. In annual plants, a trade-off between days to flower (DTF) and
      reproductive capacity often determines how many individuals survive to flower in
      a short growing season, and also influences the seed set of survivors. We develop
      a model of viability and fecundity selection informed by many experiments on the
      yellow monkeyflower, Mimulus guttatus, but applicable to many annual species. A
      viability/fecundity trade-off maintains stable polymorphism under surprisingly
      general conditions. We also introduce both spatial heterogeneity and temporal
      stochasticity in environmental parameters. Neither is necessary for polymorphism,
      but spatial heterogeneity allows polymorphism while also generating the often
      observed non-negative correlations in fitness components.

PMID- 29030893
TI  - Sonic hedgehog antagonists reduce size and alter patterning of the frog inner
      ear.
AB  - Sonic hedgehog (Shh) signaling plays a major role in vertebrate development, from
      regulation of proliferation to the patterning of various organs. In amniotes, Shh
      affects dorsoventral patterning in the inner ear but affects anteroposterior
      patterning in teleost ears. It remains unknown how altered function of Shh
      relates to morphogenetic changes that coincide with the evolution of limbs and
      novel auditory organs in the ear. In this study, we used the tetrapod, Xenopus
      laevis, to test how increasing concentrations of the Shh signal pathway
      antagonist, Vismodegib, affects ear development. Vismodegib treatment dose
      dependently alters the development of the ear, hypaxial muscle, and indirectly
      the Mauthner cell through its interaction with the inner ear afferents. Together,
      these phenotypes have an effect on escape response. The altered Mauthner cell
      likely contributes to the increased time to respond to a stimulus. In addition,
      the increased hypaxial muscle in the trunk likely contributes to the subtle
      change in animal C-start flexion angle. In the ear, Vismodegib treatment results
      in decreasing segregation between the gravistatic sensory epithelia as the
      concentration of Vismodegib increases. Furthermore, at higher doses, there is a
      loss of the horizontal canal but no enantiomorphic transformation, as in bony
      fish lacking Shh. Like in amniotes, Shh signaling in frogs affects dorsoventral
      patterning in the ear, suggesting that auditory sensory evolution in
      sarcopterygians/tetrapods evolved with a shift of Shh function in axis
      specification. (c) 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1385-1400,
      2017.

PMID- 29030896
TI  - How good are the current guidelines on endometriosis?

PMID- 29030894
TI  - Pooled efficacy and safety of eslicarbazepine acetate as add-on treatment in
      patients with focal-onset seizures: Data from four double-blind placebo
      controlled pivotal phase III clinical studies.
AB  - PURPOSE: Pooled evaluation of the key efficacy and safety profile of
      eslicarbazepine acetate (ESL) added-on to stable antiepileptic therapy in adults
      with focal-onset seizures. METHODS: Data from 1703 patients enrolled in four
      phase III double-blind, randomized, placebo-controlled studies were pooled and
      analyzed. Following a 2 week titration period, ESL was administered at 400 mg,
      800 mg, and 1200 mg once-daily doses for 12 weeks (maintenance period). Pooled
      efficacy variable was standardized (/4 weeks) seizure frequency (SSF) analyzed
      over the maintenance period as reduction in absolute and relative SSF and
      proportion of responders (>=50% reduction in SSF). Pooled safety was analyzed by
      means of adverse events and clinical laboratory assessments. RESULTS: SSF was
      significantly reduced with ESL 800 mg (P < 0.0001) and 1200 mg (P < 0.0001)
      compared to placebo. Median relative reduction in SSF was 33.4% for ESL 800 mg
      and 37.8% for 1200 mg (placebo: 17.6%), and responder rate was 33.8% and 43.1%
      (placebo: 22.2%). ESL was more efficacious than placebo regardless of gender,
      geographical region, epilepsy duration, age at time of diagnosis, seizure type,
      and type of concomitant antiepileptic drugs (AED). Incidence of adverse events
      (AEs) and AEs leading to discontinuation was dose dependent. Most common AEs
      (>10% patients) were dizziness, somnolence, and nausea. The incidence of
      treatment-emergent AEs (dizziness, somnolence, ataxia, vomiting, and nausea) was
      lower in patients who began taking ESL 400 mg (followed by 400 mg increments to
      800 or 1200 mg) than in those who began taking ESL 600 mg or 800 mg. CONCLUSIONS:
      Once-daily ESL 800 mg and 1200 mg showed consistent results across all efficacy
      and safety endpoints, independent of study population characteristics and type of
      concomitant AEDs. Treatment initiated with ESL 400 mg followed by 400 mg
      increments to 800 or 1200 mg provides optimal balance of efficacy and
      tolerability.

PMID- 29030897
TI  - Stillbirth prevention: the challenges of public campaigns.

PMID- 29030898
TI  - Surgical innovation for obstetric fistula patients.

PMID- 29030899
TI  - Responses of the soil fungal communities to the co-invasion of two invasive
      species with different cover classes.
AB  - Soil fungal communities play an important role in the successful invasion of non
      native species. It is common for two or more invasive plant species to co-occur
      in invaded ecosystems. This study aimed to determine the effects of co-invasion
      of two invasive species (Erigeron annuus and Solidago canadensis) with different
      cover classes on soil fungal communities using high-throughput sequencing.
      Invasion of E. annuus and/or S. canadensis had positive effects on the sequence
      number, operational taxonomic unit (OTU) richness, Shannon diversity, abundance
      based cover estimator (ACE index) and Chao1 index of soil fungal communities, but
      negative effects on the Simpson index. Thus, invasion of E. annuus and/or S.
      canadensis could increase diversity and richness of soil fungal communities but
      decrease dominance of some members of these communities, in part to facilitate
      plant further invasion, because high soil microbial diversity could increase soil
      functions and plant nutrient acquisition. Some soil fungal species grow well,
      whereas others tend to extinction after non-native plant invasion with increasing
      invasion degree and presumably time. The sequence number, OTU richness, Shannon
      diversity, ACE index and Chao1 index of soil fungal communities were higher under
      co-invasion of E. annuus and S. canadensis than under independent invasion of
      either individual species. The co-invasion of the two invasive species had a
      positive synergistic effect on diversity and abundance of soil fungal
      communities, partly to build a soil microenvironment to enhance competitiveness
      of the invaders. The changed diversity and community under co-invasion could
      modify resource availability and niche differentiation within the soil fungal
      communities, mediated by differences in leaf litter quality and quantity, which
      can support different fungal/microbial species in the soil.

PMID- 29030900
TI  - Computational flow cytometry analysis reveals a unique immune signature of the
      human maternal-fetal interface.
AB  - PROBLEM: Decidual immune dysregulation is thought to underlie major pregnancy
      disorders; however, incomplete understanding of the decidual immune interface has
      hampered the mechanistic investigation. METHOD OF STUDY: Human term decidua was
      collected, and single-cell phenotypic information was acquired by highly
      polychromatic flow cytometry. Cellular identity analysis was performed with t
      distributed stochastic neighbor embedding, DensVM clustering, and matched to
      CellOntology database. RESULTS: Traditional analytical methods validated known
      cellular T and dendritic cell subsets in human term decidua. Computational
      analysis revealed a complex and tissue-specific decidual immune signature in both
      the innate and adaptive immune compartments. CONCLUSION: Polychromatic flow
      cytometry with a streamlined computational analysis pipeline is a feasible
      approach to comprehensive immunome mapping of human term decidua. As an unbiased,
      standardized method of investigation, computational flow cytometry promises to
      unravel the immune pathology of pregnancy disorders.

PMID- 29030902
TI  - The prognostic significance of early and late right precordial lead (V4 R) ST
      segment elevation in patients with acute anterior myocardial infarction.
AB  - BACKGROUND: The predictive significance of ST-segment elevation (STE) in lead V4
      R in patients with anterior ST-segment elevation myocardial infarction (STEMI)
      has not been well-understood. In this study, we evaluated the prognostic value of
      early and late STE in lead V4 R in patients with anterior STEMI. METHODS: A total
      451 patients with anterior STEMI who treated with primary percutaneous coronary
      intervention (PPCI) were prospectively enrolled in this study. All patients were
      classified according to presence of STE (>1 mm) in lead V4 R at admission and/or
      60 min after PPCI. Based on this classification, all patients were divided into
      three subgroups as no V4 R STE (Group 1), early but not late V4 R STE (Group 2)
      and late V4 R STE (Group 3). RESULTS: In-hospital mortality had higher rates at
      group 2 and 3 and that had 2.1 and 4.1-times higher mortality than group 1. Late
      V4 R STE remained as an independent risk factor for cardiogenic shock (odds ratio
      [OR] 2.6; 95% confidence interval [CI] 1.9-4.3; p < .001) and in-hospital
      mortality (OR 2.3; 95% CI 1.8-4.1; p < .001). The 12-month overall survival for
      group 1, 2, and 3 were 91.1%, 82.4%, and 71.4% respectively. However, the long
      term mortality also had the higher rate at group 3; late V4 R STE did not remain
      as an independent risk factor for long-term mortality (OR 1.5; 95% CI 0.8-4.1; p:
      .159). CONCLUSION: Late V4 R STE in patients with anterior STEMI is strongly
      associated with poor prognosis. The record of late V4 R in patients with anterior
      STEMI has an important prognostic value.

PMID- 29030901
TI  - Disrupted integration of exteroceptive and interoceptive signaling in autism
      spectrum disorder.
AB  - : In addition to deficits in social communication, individuals diagnosed with
      Autism Spectrum Disorder (ASD) frequently exhibit changes in sensory and
      multisensory function. Recent evidence has focused on changes in audiovisual
      temporal processing, and has sought to relate these sensory-based changes to
      weaknesses in social communication. These changes in audiovisual temporal
      function manifest as differences in the temporal epoch or "window" within which
      paired auditory and visual stimuli are integrated or bound, with those with ASD
      exhibiting expanded audiovisual temporal binding windows (TBWs). However, it is
      unknown whether this impairment is unique to audiovisual pairings, perhaps
      because of their relevance for speech processing, or whether it generalizes
      across pairings in different sensory modalities. In addition to the exteroceptive
      senses, there has been growing interest in ASD research in interoception (e.g.,
      the monitoring of respiration, heartbeat, hunger, etc.), as these internally
      directed sensory processes appear to be altered as well in autism. In the current
      study, we sought to examine both exteroception and interoception in individuals
      with ASD and a group of typically developing (TD) matched controls, with an
      emphasis on temporal perception of audiovisual (exteroceptive) and cardiovisual
      (interoceptive to exteroceptive) cues. Results replicate prior findings showing
      expanded audiovisual TBWs in ASD in comparison to TD. In addition, strikingly,
      cardiovisual TBWs were fourfold larger in ASD than in TD, suggesting a putative
      complete lack of cardiovisual temporal acuity in ASD individuals. Results are
      discussed in light of recent evidence indicating a reduced tendency to rely on
      sensory priors in ASD. Autism Res 2018, 11: 194-205. (c) 2017 International
      Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Studies have
      shown that individuals with autism have difficulty in separating auditory and
      visual events in time. People with autism also weight sensory evidence
      originating from the external world and from their body differently. We measured
      simultaneity judgments regarding visual and auditory events and between visual
      and heartbeat events. Results suggest that while individuals with autism show
      unusual temporal function across the senses in a general manner, this deficit is
      greater when pairings bridged between the external world and the internal body.

PMID- 29030903
TI  - Increased water-use efficiency translates into contrasting growth patterns of
      Scots pine and sessile oak at their southern distribution limits.
AB  - In forests, the increase in atmospheric CO2 concentrations (Ca ) has been related
      to enhanced tree growth and intrinsic water-use efficiency (iWUE). However, in
      drought-prone areas such as the Mediterranean Basin, it is not yet clear to what
      extent this "fertilizing" effect may compensate for drought-induced growth
      reduction. We investigated tree growth and physiological responses at five Scots
      pine (Pinus sylvestris L.) and five sessile oak (Quercus petraea (Matt.) Liebl.)
      sites located at their southernmost distribution limits in Europe for the period
      1960-2012 using annually resolved tree-ring width and delta13 C data to track
      ecophysiological processes. Results indicated that all 10 natural stands
      significantly increased their leaf intercellular CO2 concentration (Ci ), and
      consequently iWUE. Different trends in the theoretical gas-exchange scenarios as
      a response to increasing Ca were found: generally, Ci tended to increase
      proportionally to Ca , except for trees at the driest sites in which Ci remained
      constant. Ci from the oak sites displaying higher water availability tended to
      increase at a comparable rate to Ca . Multiple linear models fitted at site level
      to predict basal area increment (BAI) using iWUE and climatic variables better
      explained tree growth in pines (31.9%-71.4%) than in oak stands (15.8%-46.8%).
      iWUE was negatively linked to pine growth, whereas its effect on growth of oak
      differed across sites. Tree growth in the western and central oak stands was
      negatively related to iWUE, whereas BAI from the easternmost stand was positively
      associated with iWUE. Thus, some Q. petraea stands might have partially benefited
      from the "fertilizing" effect of rising Ca , whereas P. sylvestris stands due to
      their strict closure of stomata did not profit from increased iWUE and
      consequently showed in general growth reductions across sites. Additionally, the
      inter-annual variability of BAI and iWUE displayed a geographical polarity in the
      Mediterranean.

PMID- 29030905
TI  - Comparing the effects of age, pubertal development, and symptom profile on
      cortisol rhythm in children and adolescents with autism spectrum disorder.
AB  - : Previous studies in children with autism spectrum disorder (ASD) have shown
      elevated evening cortisol; however, few studies have examined diurnal rhythm in
      adolescents with ASD. Adolescence is a time of significant physical and
      psychological change, and dysregulation of the hypothalamic-pituitary-adrenal
      axis may put adolescents with ASD at increased risk for internalizing disorders,
      such as anxiety and depression. The extent to which cortisol levels are
      associated with age, puberty and symptom profile was examined in 113 youth (ages
      7-17) with ASD and typical development. Salivary samples were collected over 3
      days in the home, 4 times per day (waking, 30-min post-waking, afternoon,
      evening). Results showed youth with ASD had higher evening cortisol and a blunted
      diurnal slope relative to TD youth. Pubertal development and age were significant
      predictors of evening cortisol, and adolescents with ASD had higher evening
      cortisol levels compared to children with ASD. The study extends previous reports
      of elevated evening cortisol in children with ASD to reveal high levels in
      adolescence as well. Adolescents with ASD also show a significantly blunted
      diurnal slope, which may be associated with risk of internalizing symptoms.
      Findings suggest elevated evening cortisol persists across development in youth
      with ASD, thus emphasizing a need to identify potential negative effects of
      excess cortisol exposure on health in ASD individuals. Autism Res 2018, 11: 110
      120. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
      LAY SUMMARY: Elevations in stress hormone, cortisol, during the evening may
      indicate increased stress from changes throughout the day in youth with autism
      spectrum disorder (ASD). The current study shows that age and pubertal
      development are also related to increases in evening cortisol, and this
      maladaptive elevation in cortisol in ASD is not going away with age. These
      cortisol elevations may also be associated with other psychological symptoms and
      warrant further investigation in adolescents with ASD.

PMID- 29030904
TI  - Development and maintenance of the brain's immune toolkit: Microglia and non
      parenchymal brain macrophages.
AB  - Microglia and non-parenchymal macrophages located in the perivascular space, the
      meninges and the choroid plexus are independent immune populations that play
      vital roles in brain development, homeostasis, and tissue healing. Resident
      macrophages account for a significant proportion of cells in the brain and their
      density remains stable throughout the lifespan thanks to constant turnover.
      Microglia develop from yolk sac progenitors, later evolving through intermediate
      progenitors in a fine-tuned process in which intrinsic factors and external
      stimuli combine to progressively sculpt their cell type-specific transcriptional
      profiles. Recent evidence demonstrates that non-parenchymal macrophages are also
      generated during early embryonic development. In recent years, the development of
      powerful fate mapping approaches combined with novel genomic and transcriptomic
      methodologies have greatly expanded our understanding of how brain macrophages
      develop and acquire specialized functions, and how cell population dynamics are
      regulated. Here, we review the transcription factors, epigenetic remodeling, and
      signaling pathways orchestrating the embryonic development of microglia and non
      parenchymal macrophages. Next, we describe the dynamics of the macrophage
      populations of the brain and discuss the role of progenitor cells, to gain a
      better understanding of their functions in the healthy and diseased brain. (c)
      2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 561-579, 2018.

PMID- 29030906
TI  - Effects of interruptions of external beam radiation therapy on outcomes in
      patients with prostate cancer.
AB  - INTRODUCTION: To evaluate if interruptions of external beam radiation therapy
      impact outcomes in men with localized prostate cancer (PCa). METHODS: We included
      men with localized PCa treated with three-dimensional conformal radiotherapy (3D
      CRT) or intensity-modulated radiation therapy (IMRT) of escalated dose (>=74 Gy
      in 1.8 or 2 Gy fractions) between 1992 and 2013 at an NCI-designated cancer
      centre. Men receiving androgen deprivation therapy were excluded. The non
      treatment day ratio (NTDR) was defined as the number of non-treatment days
      divided by the total elapsed days of therapy. NTDR was analysed for each National
      Comprehensive Cancer Network (NCCN) risk group. RESULTS: There were 1728 men
      included (839 low-risk, 776 intermediate-risk and 113 high-risk), with a median
      follow up of 53.5 months (range 12-185.8). The median NTDR was 31% (range 23
      71%), translating to approximately 2 breaks (each break represents a missed
      treatment that will be made up) for 8 weeks of RT with 5 treatments per week. The
      75 percentile of NTDR was 33%, translating to approximately 4 breaks, which was
      used as the cutoff for analysis. There were no significant differences in freedom
      from biochemical failure, freedom from distant metastasis, cancer specific
      survival, or overall survival for men with NTDR >=33% compared to NTDR<33% for
      each risk group. Multivariable analyses including NTDR, age, race, Gleason score,
      T stage, and PSA were performed using the proportional hazards regression
      procedure. NTDR>=33% was not significantly associated with increased hazard ratio
      for outcomes in each risk group compared to NTDR<33%. CONCLUSION: Unintentional
      treatment breaks during dose escalated external beam radiation therapy for PCa
      did not cause a significant difference in outcomes, although duration of follow
      up limits the strength of this conclusion.

PMID- 29030907
TI  - Macromolecular rate theory (MMRT) provides a thermodynamics rationale to underpin
      the convergent temperature response in plant leaf respiration.
AB  - Temperature is a crucial factor in determining the rates of ecosystem processes,
      for example, leaf respiration (R) - the flux of plant respired CO2 from leaves to
      the atmosphere. Generally, R increases exponentially with temperature and
      formulations such as the Arrhenius equation are widely used in earth system
      models. However, experimental observations have shown a consequential and
      consistent departure from an exponential increase in R. What are the principles
      that underlie these observed patterns? Here, we demonstrate that macromolecular
      rate theory (MMRT), based on transition state theory (TST) for enzyme-catalyzed
      kinetics, provides a thermodynamic explanation for the observed departure and the
      convergent temperature response of R using a global database. Three meaningful
      parameters emerge from MMRT analysis: the temperature at which the rate of
      respiration would theoretically reach a maximum (the optimum temperature, Topt ),
      the temperature at which the respiration rate is most sensitive to changes in
      temperature (the inflection temperature, Tinf ) and the overall curvature of the
      log(rate) versus temperature plot (the change in heat capacity for the system,
      DeltaCP?). On average, the highest potential enzyme-catalyzed rates of
      respiratory enzymes for R are predicted to occur at 67.0 +/- 1.2 degrees C and
      the maximum temperature sensitivity at 41.4 +/- 0.7 degrees C from MMRT. The
      average curvature (average negative DeltaCP?) was -1.2 +/- 0.1 kJ mol-1  K-1 .
      Interestingly, Topt , Tinf and DeltaCP? appear insignificantly different across
      biomes and plant functional types, suggesting that thermal response of
      respiratory enzymes in leaves could be conserved. The derived parameters from
      MMRT can serve as thermal traits for plant leaves that represent the collective
      temperature response of metabolic respiratory enzymes and could be useful to
      understand regulations of R under a warmer climate. MMRT extends the classic TST
      to enzyme-catalyzed reactions and provides an accurate and mechanistic model for
      the short-term temperature response of R around the globe.

PMID- 29030908
TI  - Epidemiology of infertility in China: a population-based study.
AB  - OBJECTIVE: To assess the current prevalence of and risk factors for infertility
      among couples of reproductive age in China. DESIGN: Population-based cross
      sectional study. SETTING: We approached 25 270 couples in eight
      provinces/municipalities, of whom 18 571 (response rate 74%) were interviewed.
      POPULATION: Couples living together and married for more than 1 year, of whom the
      female spouse was 20-49 years old. METHODS: Women were approached via telephone
      and face-to-face conversation to complete the standardised and structured
      questionnaire by trained interviewers. MAIN OUTCOME MEASURES: Prevalence of and
      risk factors for infertility. RESULTS: Among women 'at risk' of pregnancy, the
      prevalence of infertility was 15.5% (2680/17 275). Among 10 742 women attempting
      to become pregnant, the prevalence of infertility was 25.0% (2680/10 742), which
      increased with age in the second population. Among women who failed to achieve
      pregnancy in the last 12 months, 3470 finished our questionnaire about fertility
      care, and 55.2% (1915/3470) of them had sought medical help. Sociodemographic
      risk factors for infertility included lower educational level [adjusted odds
      ratio (aOR) 3.4, 95% CI 2.0-5.5] and employment (aOR 2.3, 95% CI 1.9-2.9).
      Clinical risk factors were irregular menstrual cycle (aOR 1.8, 95% CI 1.2-2.5),
      light menstrual blood volume (aOR 1.6, 95% CI 1.2-2.0), history of cervicitis
      (aOR 1.5, 95% CI 1.2-2.0) and endometriosis (aOR 3.1, 95% CI 1.1-9.3), previous
      stillbirth (aOR 2.1, 95% CI 1.3-3.3) and miscarriage (aOR 2.7, 95% CI 2.1-3.5).
      In addition, history of operation was a significant risk factor of infertility.
      CONCLUSIONS: Among couples of reproductive age in China, the prevalence of
      infertility was 25%, and almost half of the couples experiencing infertility had
      not sought medical help. TWEETABLE ABSTRACT: In China, 25% of couples actively
      attempting to become pregnant suffered infertility.

PMID- 29030909
TI  - Global gene expression profiles of hematopoietic stem and progenitor cells from
      patients with chronic myeloid leukemia: the effect of in vitro culture with or
      without imatinib.
AB  - In this study, we determined the gene expression profiles of bone marrow-derived
      cell fractions, obtained from normal subjects and Chronic Myeloid Leukemia (CML)
      patients, that were highly enriched for hematopoietic stem (HSCs) and progenitor
      (HPCs) cells. Our results indicate that the profiles of CML HSCs and HPCs were
      closer to that of normal progenitors, whereas normal HSCs showed the most
      different expression profile of all. We found that the expression profiles of
      HSCs and HPCs from CML marrow were closer to each other than those of HSCs and
      HPCs from normal marrow. The major biologic processes dysregulated in CML cells
      included DNA repair, cell cycle, chromosome condensation, cell adhesion, and the
      immune response. We also determined the genomic changes in both normal and CML
      progenitor cells under culture conditions, and found that several genes involved
      in cell cycle, steroid biosynthesis, and chromosome segregation were upregulated,
      whereas genes involved in transcription regulation and apoptosis were
      downregulated. Interestingly, these changes were the same, regardless of the
      addition of Imatinib (IM) to the culture. Finally, we identified three genes
      PIEZO2, RXFP1, and MAMDC2- that are preferentially expressed by CML primitive
      cells and that encode for cell membrane proteins; thus, they could be used as
      biomarkers for CML stem cells.

PMID- 29030910
TI  - The role of general psychosocial factors for the use of cancer screening-Findings
      of a population-based observational study among older adults in Germany.
AB  - Within the framework of the health-belief model, some studies exist investigating
      the association between illness-specific psychosocial factors and the use of
      cancer screenings. However, studies investigating the association between general
      psychosocial factors and the use of cancer screenings are missing. Thus, this
      study aimed at examining the association between well-established general
      psychosocial factors and the use of cancer screenings. Data were gathered from a
      large, population-based sample of community-dwelling individuals aged 40 and
      above in Germany (n = 7673; in 2014). Loneliness, cognitive well-being, affective
      well-being (negative and positive affect), optimism, self-efficacy, self-esteem,
      self-regulation, perceived autonomy, perceived stress, and perceived social
      exclusion were used as general psychosocial factors. Furthermore, individuals
      were asked whether they regularly underwent early cancer screening in the past
      years (yes; no). A total of 65.6% of the individuals used cancer screening.
      Adjusting for sociodemographic factors, self-rated health, morbidity and
      lifestyle factors, multiple logistic regressions revealed that the use of cancer
      screening is positively associated with decreased loneliness, cognitive well
      being, optimism, self-efficacy, self-esteem, self-regulation, perceived autonomy,
      decreased perceived stress, decreased perceived social exclusion, and positive
      affect, while it is not associated with negative affect. This study stresses the
      strong association between general psychosocial factors and the use of cancer
      screening. This knowledge might be fruitful to address individuals at risk for
      underuse.

PMID- 29030912
TI  - The development and implementation of a performance appraisal framework for
      radiation therapists in planning and simulation.
AB  - It is a challenge for radiation therapists (RTs) to keep pace with changing
      planning technology and techniques while maintaining appropriate skills levels.
      The ability of individual RTs to meet the demands of this constantly changing
      practice can only be assured through establishing clearly defined standards for
      practice and a systematic process for providing feedback on performance.
      Investigation into existing models for performance appraisal produced minimal
      results so a radiation therapy-specific framework was developed. The goal for
      this initiative was to establish a framework that would reflect the complexity of
      practice and provide a clear measure of performance against them. This paper
      outlines the implementation of this framework into practice and discusses some
      lessons learned in the process. The framework was developed and implemented in
      six stages: (1) project team, (2) scope, (3) dosimetry pilot, (4) staff
      consultation, (5) finalisation and implementation and (6) future development and
      evaluation. Both cultural and organisational obstacles needed to be addressed
      before this framework could be successfully introduced. Even though this slowed
      progress, addressing these obstacles during the development process was essential
      to the success of this framework. The incremental approach provided the
      opportunity for each aspect to be tested and the development of subsequent stages
      to be informed by lessons learned during the previous one. This approach may be
      beneficial when developing and implementing projects involving performance
      appraisal to promote consistency, fairness and quality.

PMID- 29030911
TI  - Phosphorylated ERK is a potential prognostic biomarker for Sorafenib response in
      hepatocellular carcinoma.
AB  - Sorafenib, the only approved drug for hepatocellular carcinoma, acts as a
      remarkable inhibitor of Raf serine-threonine kinases. However, Sorafenib is
      expensive, and clinical experience shows that it is not an effective treatment
      for many patients. Previous study has demonstrated that phosphorylated ERK (pERK)
      is a key downstream component in the RAF/MEK/ERK signaling pathway. Here, we
      investigate whether pERK is a useful biomarker for treating HCC with Sorafenib.
      In vitro cell viability assays showed that the efficacy of Sorafenib was
      distinctly different according to the level of pERK. Furthermore, in established
      patient-derived xenografts from HCC specimens, we found that the growth rate of
      tumors with high levels of pERK was significantly decreased by Sorafenib
      treatment. Taken together, pERK is a potential biomarker for the sensitivity to
      Sorafenib in treating HCC.

PMID- 29030913
TI  - Effect of water restriction on milk yield and quality in Lacaune breed ewes.
AB  - The effect of water restriction on body weight, body condition score, milk yield,
      and milk composition and rheological characteristics in intensively reared
      Lacaune ewes was evaluated. After 7 days of adaptation, the trial lasted 28 days.
      Thirty lactating ewes (48 +/- 5 months of age; mean value +/- standard deviation)
      at the beginning of third lactation month were divided into three groups (n =
      10), corresponding to the following water restriction treatment: a group control
      received no drinking water restriction (W100), and two groups received water to
      the extent of 80% and 60% of W100 daily consumption (W80 and W60 group
      respectively). The effects of water restriction were assessed at the beginning of
      experiment (D0), at D14 and D28. The W60 group resulted in a significant decrease
      in body weight, body condition score, milk yield and feed consumption of hay due
      to the experimental treatment; whereas a marked increase in both W60 and W80
      groups of milk lactose, urea, sodium, sodium chloride content and titratable
      acidity was observed. Rheological parameters of milk, rennet coagulation time and
      curd-firming time were positively affected by water restriction treatments, with
      a decrease in both experimental groups of the time required for the formation of
      a stable and firm curd. Results highlight the importance of water consumption in
      dairy sheep. The scarce availability of water, significantly affecting ewes milk
      production, is worthy of particular attention in arid area where water stress
      resistant breeds should be considered. This study underlines that milk yield,
      being closely linked to the availability of water of the breeding habitat due to
      its high water content (about 81%), could be reached in area where water is not a
      limiting factor without reducing the genetic expression of the animals. Less
      severe water restrictions, such as 20% of daily voluntary water intake, produce
      no detrimental effect on milk yield.

PMID- 29030914
TI  - PufQ regulates porphyrin flux at the haem/bacteriochlorophyll branchpoint of
      tetrapyrrole biosynthesis via interactions with ferrochelatase.
AB  - Facultative phototrophs such as Rhodobacter sphaeroides can switch between
      heterotrophic and photosynthetic growth. This transition is governed by oxygen
      tension and involves the large-scale production of bacteriochlorophyll, which
      shares a biosynthetic pathway with haem up to protoporphyrin IX. Here, the
      pathways diverge with the insertion of Fe2+ or Mg2+ into protoporphyrin by
      ferrochelatase or magnesium chelatase, respectively. Tight regulation of this
      branchpoint is essential, but the mechanisms for switching between respiratory
      and photosynthetic growth are poorly understood. We show that PufQ governs the
      haem/bacteriochlorophyll switch; pufQ is found within the oxygen-regulated
      pufQBALMX operon encoding the reaction centre-light-harvesting photosystem
      complex. A pufQ deletion strain synthesises low levels of bacteriochlorophyll and
      accumulates the biosynthetic precursor coproporphyrinogen III; a suppressor
      mutant of this strain harbours a mutation in the hemH gene encoding
      ferrochelatase, substantially reducing ferrochelatase activity and increasing
      cellular bacteriochlorophyll levels. FLAG-immunoprecipitation experiments
      retrieve a ferrochelatase-PufQ-carotenoid complex, proposed to regulate the
      haem/bacteriochlorophyll branchpoint by directing porphyrin flux toward
      bacteriochlorophyll production under oxygen-limiting conditions. The co-location
      of pufQ and the photosystem genes in the same operon ensures that switching of
      tetrapyrrole metabolism toward bacteriochlorophyll is coordinated with the
      production of reaction centre and light-harvesting polypeptides.

PMID- 29030917
TI  - Discovery of new QTLs underlying hybrid fertility and reproductive isolation in
      rice.

PMID- 29030915
TI  - Political transition and emergent forest-conservation issues in Myanmar.
AB  - Political and economic transitions have had substantial impacts on forest
      conservation. Where transitions are underway or anticipated, historical precedent
      and methods for systematically assessing future trends should be used to
      anticipate likely threats to forest conservation and design appropriate and
      prescient policy measures to counteract them. Myanmar is transitioning from an
      authoritarian, centralized state with a highly regulated economy to a more
      decentralized and economically liberal democracy and is working to end a long
      running civil war. With these transitions in mind, we used a horizon-scanning
      approach to assess the 40 emerging issues most affecting Myanmar's forests,
      including internal conflict, land-tenure insecurity, large-scale agricultural
      development, demise of state timber enterprises, shortfalls in government revenue
      and capacity, and opening of new deforestation frontiers with new roads, mines,
      and hydroelectric dams. Averting these threats will require, for example,
      overhauling governance models, building capacity, improving infrastructure- and
      energy-project planning, and reforming land-tenure and environmental-protection
      laws. Although challenges to conservation in Myanmar are daunting, the political
      transition offers an opportunity for conservationists and researchers to help
      shape a future that enhances Myanmar's social, economic, and environmental
      potential while learning and applying lessons from other countries. Our approach
      and results are relevant to other countries undergoing similar transitions.

PMID- 29030918
TI  - Simple technique for management of anterior chamber-migrated Ozurdex(r) implant.

PMID- 29030916
TI  - Identification and characterization of a metastatic suppressor BRMS1L as a target
      gene of p53.
AB  - The tumor suppressor p53 and its family members, p63 and p73, play a pivotal role
      in the cell fate determination in response to diverse upstream signals. As
      transcription factors, p53 family proteins regulate a number of genes that are
      involved in cell cycle arrest, apoptosis, senescence, and maintenance of genomic
      stability. Recent studies revealed that p53 family proteins are important for the
      regulation of cell invasion and migration. Microarray analysis showed that breast
      cancer metastasis suppressor 1-like (BRMS1L) is upregulated by p53 family
      proteins, specifically p53, TAp63gamma, and TAp73beta. We identified two
      responsive elements of p53 family proteins in the first intron and upstream of
      BRMS1L. These response elements are well conserved among mammals. Functional
      analysis showed that ectopic expression of BRMS1L inhibited cancer cell invasion
      and migration; knockdown of BRMS1L by siRNA induced the opposite effect.
      Importantly, clinical databases revealed that reduced BRMS1L expression
      correlated with poor prognosis in patients with breast and brain cancer.
      Together, these results strongly indicate that BRMS1L is one of the mediators
      downstream of the p53 pathway, and that it inhibits cancer cell invasion and
      migration, which are essential steps in cancer metastasis. Collectively, our
      results indicate that BRMS1L is involved in cancer cell invasion and migration,
      and could be a therapeutic target for cancer.

PMID- 29030920
TI  - Identification of sesame (Sesamum indicum L.) chromosomes using the BAC-FISH
      system.
AB  - Sesame (Sesamum indicum L.; Pedaliaceae) is a commercially valuable oilseed crop
      with high oil content. Its small genome size favours the genomic analysis of key
      biological processes, such as oil synthesis and metabolism. However, the 13
      chromosome pairs of sesame have not been characterised because of technological
      limitations and their small size. We constructed a BAC library comprising 57,600
      BAC clones for sesame. The estimated genome coverage of the sesame BAC library
      was 13.8*. The successive double colour fluorescence in situ hybridisation (FISH)
      with bacterial artificial chromosomes (BACs) for sesame was established in this
      study. Subsequently, the 13 sesame chromosome pairs were individually
      differentiated using 17 specific BACs for the first time. The schematic of the
      sesame chromosome set was drawn according to the chromosome relative length and
      relative position of the BAC signal. The cytogenetic characteristics of sesame
      chromosomes were also explored. The results provide the technical background
      required for further cytogenetic map construction, genome assembly and
      localisation of the DNA sequence in sesame.

PMID- 29030919
TI  - Baseline fragmented QRS increases the risk of major arrhythmic events in Brugada
      syndrome: Systematic review and meta-analysis.
AB  - BACKGROUND: Fragmented QRS reflects disturbances in the myocardium predisposing
      the heart to ventricular tachyarrhythmias. Recent studies suggest that fragmented
      QRS (fQRS) is associated with major arrhythmic events in Brugada syndrome.
      However, a systematic review and meta-analysis of the literature has not been
      done. We assessed the association between fQRS and major arrhythmic events in
      Brugada syndrome by a systematic review of the literature and a meta-analysis.
      METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from
      inception to May 2017. Included studies were published prospective or
      retrospective cohort studies that compared major arrhythmic events (ventricular
      fibrillation, sustained ventricular tachycardia, sudden cardiac arrest, or sudden
      cardiac death) in Brugada syndrome with fQRS versus normal QRS. Data from each
      study were combined using the random-effects, generic inverse variance method of
      DerSimonian and Laird to calculate risk ratios and 95% confidence intervals.
      RESULTS: Nine studies from January 2012 to May 2017 were included in this meta
      analysis involving 2,360 subjects with Brugada syndrome (550 fQRS and 1,810 non
      fQRS). Fragmented QRS was associated with major arrhythmic events (pooled risk
      ratio =3.36, 95% confidence interval: 2.09-5.38, p < .001, I2  = 50.9%) as well
      as fatal arrhythmia (pooled risk ratio =3.09, 95% confidence interval: 1.40-6.86,
      p = .005, I2  = 69.7%). CONCLUSIONS: Baseline fQRS increased major arrhythmic
      events up to 3-fold. Our study suggests that fQRS could be an important tool for
      risk assessment in patients with Brugada syndrome.

PMID- 29030921
TI  - Development of short-range white matter in healthy children and adolescents.
AB  - Neural communication is facilitated by intricate networks of white matter (WM)
      comprised of both long and short range connections. The maturation of long range
      WM connections has been extensively characterized, with projection, commissural,
      and association tracts showing unique trajectories with age. There, however,
      remains a limited understanding of age-related changes occurring within short
      range WM connections, or U-fibers. These connections are important for local
      connectivity within lobes and facilitate regional cortical function and greater
      network economy. Recent studies have explored the maturation of U-fibers
      primarily using cross-sectional study designs. Here, we analyzed diffusion tensor
      imaging (DTI) data for healthy children and adolescents in both a cross-sectional
      (n = 78; mean age = 13.04 +/- 3.27 years) and a primarily longitudinal (n = 26;
      mean age = 10.78 +/- 2.69 years) cohort. We found significant age-related
      differences in fractional anisotropy (FA), mean diffusivity (MD), axial
      diffusivity (AD) and radial diffusivity (RD) across the frontal, parietal, and
      temporal lobes of participants within the cross-sectional cohort. By contrast, we
      report significant age-related differences in only FA for participants within the
      longitudinal cohort. Specifically, larger FA values were observed with age in
      frontal, parietal, and temporal lobes of the left hemisphere. Our results extend
      previous findings restricted to long range WM to demonstrate regional changes in
      the microstructure of short range WM during childhood and adolescence. These
      changes possibly reflect continued myelination and axonal organization of short
      range WM with increasing age in more anterior regions of the left hemisphere. Hum
      Brain Mapp 39:204-217, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29030923
TI  - Does cardiac resynchronization therapy restore peripheral circulatory
      homeostasis?
AB  - AIMS: To evaluate whether peripheral circulatory 'remodelling' as measured by
      changes in vascular compliance and in markers of nitric oxide signalling
      contributes to patient response to cardiac resynchronization therapy (CRT).
      METHODS AND RESULTS: Effects of CRT were evaluated in 33 patients pre-procedure
      and 6 months post-procedure. Peak oxygen consumption, 6 min walk distance, New
      York Heart Association class, and quality of life score were evaluated.
      Augmentation index and its interactions with nitric oxide (NO) were evaluated by
      applanation tonometry. Platelet NO responsiveness and content of thioredoxin
      interacting protein were assessed. Plasma concentrations of N-terminal proBNP,
      asymmetric and symmetric dimethylarginine (SDMA), high sensitivity C-reactive
      protein, catecholamines, and matrix metalloproteinases-2 and -9 were assessed.
      Despite significant improvement in 6 min walk distance (P = 0.005), New York
      Heart Association class (P < 0.001), quality of life (P = 0.001), and all
      echocardiographic parameters post-CRT, there were no significant changes in
      augmentation index measurements, thioredoxin-interacting protein content, and
      platelet NO response. Significant falls in N-terminal proBNP (P = 0.008) and SDMA
      (P = 0.013; independent of renal function) occurred. Falls in SDMA predicted
      reduction in high-sensitivity C-reactive protein (P = 0.04) and increases in peak
      oxygen consumption (P = 0.04). There were no correlations between changes in
      echocardiographic parameters and those in vascular function. CONCLUSIONS: These
      data suggest that the beneficial effects of CRT over 6 months are independent of
      any change in peripheral NO-related signalling. However, there is evidence that
      suppression of inflammation occurs, and its magnitude predicts extent of clinical
      improvement.

PMID- 29030922
TI  - The role of mitochondria in axon development and regeneration.
AB  - Mitochondria are dynamic organelles that undergo transport, fission, and fusion.
      The three main functions of mitochondria are to generate ATP, buffer cytosolic
      calcium, and generate reactive oxygen species. A large body of evidence indicates
      that mitochondria are either primary targets for neurological disease states and
      nervous system injury, or are major contributors to the ensuing pathologies.
      However, the roles of mitochondria in the development and regeneration of axons
      have just begun to be elucidated. Advances in the understanding of the functional
      roles of mitochondria in neurons had been largely impeded by insufficient
      knowledge regarding the molecular mechanisms that regulate mitochondrial
      transport, stalling, fission/fusion, and a paucity of approaches to image and
      analyze mitochondria in living axons at the level of the single mitochondrion.
      However, technical advances in the imaging and analysis of mitochondria in living
      neurons and significant insights into the mechanisms that regulate mitochondrial
      dynamics have allowed the field to advance. Mitochondria have now been attributed
      important roles in the mechanism of axon extension, regeneration, and axon
      branching. The availability of new experimental tools is expected to rapidly
      increase our understanding of the functions of axonal mitochondria during both
      development and later regenerative attempts. (c) 2017 Wiley Periodicals, Inc.
      Develop Neurobiol 78: 221-237, 2018.

PMID- 29030924
TI  - Longitudinal shortening of sub-epicardial myocytes in severe ischaemic
      cardiomyopathy: insights from gadolinium contrast cardiac magnetic resonance
      imaging.
AB  - We present two patients with three-vessel disease and severely depressed left
      ventricular (LV) systolic function where viability analysis by cardiac magnetic
      resonance imaging demonstrated areas of near-transmural sub-endocardial fibrosis
      and hence little chance of regaining systolic function as judged by conventional
      analysis from radial function. Despite the pessimistic cardiac magnetic resonance
      imaging analysis, however, the patients underwent full revascularization and
      regained impressive increases in LV systolic function mainly based on improved
      longitudinal systolic segment function. The cases highlight that sub-epicardial,
      longitudinally oriented myocytes can contribute to overall LV systolic function
      and suggest taking their 'piston-function' into consideration when analysing
      viability.

PMID- 29030925
TI  - Pediatric estimating endotracheal tube "4-3-2-1": A mnemonic for an age-based
      endotracheal tube selection.

PMID- 29030926
TI  - Sternal malformations and anesthetic management.
AB  - Shamberger and Welch classify sternal malformations into four types: thoracic
      ectopia cordis, cervical ectopia cordis, thoraco-abdominal ectopia cordis, and
      cleft sternum. Cleft sternum is the most common subset, with a reported incidence
      of 1 in 50,000 to 100,000 live births, representing 0.15% of all anterior chest
      wall malformations. Acostello et al further classify cleft sternum into complete
      or partial (superior, medium, inferior) with a simple superior partial cleft
      sternum being by far the most common with an orthotopic heart, intact
      pericardium, and normal skin coverage. Associated anomalies with superior partial
      cleft sternum are rare, but can include cervicofacial hemangiomas, midline raphe
      from the tip of the cleft to the umbilicus, and PHACES (posterior fossa
      malformations, facial hemangiomas, arterial anomalies with coarctation of aorta,
      cardiac defects, eye abnormalities, sternal cleft, and supraumbilical raphe)
      syndrome. The more rare inferior partial clefts are associated with thoraco
      abdominal ectopia cordis as part of the Pentalogy of Cantrell (omphalocele,
      anterior diaphragmatic hernia, sternal cleft, ectopia cordis, ventricular septal
      defect/left ventricular diverticulum). This review summarizes the current
      knowledge of all four types of sternal malformations, and provides guidance for
      optimal anesthetic and perioperative care of these children.

PMID- 29030927
TI  - Suitability of the forearm for non-invasive blood pressure measurement in
      children.
AB  - BACKGROUND: Measurement of forearm blood pressure (BP) in pediatric patients
      during general anesthesia is periodically employed despite a lack of evidence for
      this practice. Upper arm BP measurement may be impossible to perform for either
      patient or surgical reasons, and the forearm has theoretical benefits over the
      lower leg when an alternate site is required. We hypothesize that forearm BP
      measurement provides an accurate and reliable alternative to the upper arm.
      Published adult data do not support this hypothesis, and the little pediatric
      data published contain methodological shortcomings. METHODS: A dedicated,
      externally calibrated noninvasive oscillometer was used to compare BP
      measurements in the upper arm and ipsilateral forearm of pediatric patients
      undergoing general anesthesia prior to application of a surgical stimulus. Both
      upper arm BP and ipsilateral forearm BP were sequentially measured 20 seconds
      apart on 3 separate occasions with an appropriately sized cuff. The systolic,
      diastolic, and mean blood pressures were recorded under steady-state conditions.
      RESULTS: Thirty-five elective surgical patients aged 1 to 10 years were studied.
      The bias (+/-limits of agreement) for forearm minus upper arm blood pressures
      were as follows: mean BP -1.3 mm Hg (+/-7.2), diastolic BP -3.3 (+/-5.3), and
      systolic BP +3.2 mm Hg (+/-8.3). Differences greater than +/-5 mm Hg occurred in
      59% (systolic BP), 42% (diastolic BP), and 46% (mean BP) of all observations and
      greater than +/-10 mm Hg in 17% (systolic BP), 8.6% (diastolic BP), and 15% (mean
      BP). CONCLUSION: The differences within mean +/-1.96 standard deviations reside
      considerably outside the clinically accepted tolerance of +/-5 mm Hg. Thus, the
      forearm may not be used interchangeably with upper limb BP readings in
      anesthetized healthy children. Future use of the forearm for BP measurement
      requires a validated anthropomorphically appropriate forearm cuff.

PMID- 29030928
TI  - Pharmacokinetics of S-ketamine during prolonged sedation at the pediatric
      intensive care unit.
AB  - BACKGROUND: S-ketamine is the S(+)-enantiomer of the racemic mixture ketamine, an
      anesthetic drug providing both sedation and analgesia. In clinical practice,
      significant interpatient variability in drug effect of S-ketamine is observed
      during long-term sedation. AIMS: The aim of this study was to evaluate the
      pharmacokinetic variability of S-ketamine in children aged 0-18 years during long
      term sedation. Twenty-five children (median age: 0.42 years, range: 0.02-12.5)
      received continuous intravenous administrations of 0.3-3.6 mg/kg/h S-ketamine for
      sedation during mechanical ventilation. Infusion rates were adjusted to the
      desired level of sedation and analgesia based on the COMFORT-B score and Visual
      Analog Scale. Blood samples were drawn once daily at random time-points, and at 1
      and 4 hours after discontinuation of S-ketamine infusion. Time profiles of plasma
      concentrations of S-ketamine and active metabolite S-norketamine were analyzed
      using nonlinear mixed-effects modeling software. Clearance and volume of
      distribution were allometrically scaled using the 3/4 power model. RESULTS: A
      total of 86 blood samples were collected. A 2-compartment and 1-compartment model
      adequately described the PK of S-ketamine and S-norketamine, respectively. The
      typical parameter estimates for clearance and central and peripheral volumes of
      distribution were: CLS-KETAMINE =112 L/h/70 kg, V1S-KETAMINE =7.7 L/70 kg, V2S
      KETAMINE =545L/70 kg, QS-kETAMINE =196 L/h/70 kg, and CLS-NORKETAMINE =53 L/h/70
      kg. Interpatient variability of CLS-KETAMINE and CLS-NORKETAMINE was considerable
      with values of 40% and 104%, respectively, leading to marked variability in
      steady-state plasma concentrations. CONCLUSION: Substantial interpatient
      variability in pharmacokinetics in children complicates the development of
      adequate dosage regimen for continuous sedation.

PMID- 29030929
TI  - Infection prevention in pediatric anesthesia practice.
AB  - Healthcare-associated infections are an important source of morbidity and
      mortality in pediatric patients. Anesthesiologists have a unique role in
      infection prevention. Hand hygiene and anesthesia workspace decontamination
      decrease infection rates in surgical patients. Standard protocols exist for
      insertion and handling of central lines, arterial lines, and regional procedures,
      which should be strictly adhered to in order to prevent infectious complications.
      Temperature control and timely administration of antibiotics contribute to the
      prevention of surgical site infections. Education, culture shift, staff
      engagement, and effective change management are necessary for successful
      implementation of infection prevention strategies.

PMID- 29030930
TI  - Nursing initiated tracheal extubation in PACU, the risk of delegating critical
      anesthesiology tasks in the interest of speed.

PMID- 29030931
TI  - A rare case of giant tongue teratoma: Anesthetic management in low resource
      settings.

PMID- 29030932
TI  - A prospective audit of pain profiles following general and urological surgery in
      children.
AB  - BACKGROUND: Postoperative pain is frequently undertreated in children both in
      hospital and at home following discharge. Pain has both short- and long-term
      consequences for children, their families, and the healthcare system. A greater
      understanding of procedure-specific postoperative pain trajectories is required
      to improve pain management. AIM: To determine the duration and severity of acute
      postoperative pain experienced by children undergoing 8 different general and
      urological procedures (primary outcomes). Behavioral disturbance rates, nausea
      and vomiting scores, and parental satisfaction were also examined during the
      follow-up period (secondary outcomes). METHOD: Families of children (0-18 years)
      undergoing common general and urological procedures were invited to enroll in the
      study. Children's pain scores, measured using a parental proxy 0-10 numerical
      rating scale, were collected by telephone interview until pain was resolved.
      Analgesia prescribed and given, behavioral disturbance, nausea and vomiting
      scores, the method of medication education communication, and parental
      satisfaction were also measured. RESULTS: Of 360 patients recruited, 326 complete
      datasets were available. Patients underwent laparoscopic appendicectomy (57),
      open appendicectomy (19), circumcision (50), cystoscopy (52), hypospadias repair
      (22), inguinal hernia repair (51), orchidopexy (51), or umbilical hernia repair
      (24). Postoperative pain peaked on the day of or the day after surgery in all
      groups, and decreased over time. Pain lasted a median duration of 5 postoperative
      days following open appendicectomy, and 0-2 postoperative days for other
      procedures. Behavioral disturbance rates closely followed pain scores. Analgesia
      administration at home varied widely between and within groups. CONCLUSION: Pain
      management was inadequate in most of the groups studied, particularly after
      appendicectomy or umbilical hernia repair, with most children experiencing at
      least moderate pain on the day of and day after surgery. There was a need for a
      standardized management, with increased dual analgesia prescribing, to ensure
      that children receive adequate postoperative analgesia in hospital and at home.

PMID- 29030933
TI  - Technical success of the ultrasound-guided supra-inguinal fascia iliaca
      compartment block in older children and adolescents for hip arthroscopy.
AB  - BACKGROUND: Hip arthroscopic surgery is performed on older pediatric patients.
      Fascia iliaca compartment block has proven efficacy in providing analgesia
      following hip surgery and can be performed with target location of local
      anesthetic below or above the inguinal ligament. The reported success of
      ultrasound-guided infra-inguinal fascia iliaca compartment block is lower when
      compared to traditional landmark technique, while the reliability of supra
      inguinal fascia iliaca compartment block is unreported. AIM: The primary aim was
      to report the results in obtaining sensory changes in the distribution of the
      femoral and lateral femoral cutaneous nerves following supra-inguinal fascia
      iliaca compartment block in patients undergoing arthroscopic hip surgery.
      Secondary outcomes are the ability to find echogenic landmarks and to report pain
      scores and opioid consumption. METHODS: We reviewed the electronic medical record
      and regional anesthesia database of patients receiving ultrasound-guided fascia
      iliaca compartment block for arthroscopic hip surgery. Sensory changes to the
      femoral and lateral femoral cutaneous nerves were determined. Identification of
      echogenic landmarks was quantified. Pain scores and opioid consumption were
      determined. RESULTS: Seventeen patients of mean age 15.4 years old (SD 1.3; range
      13-17 years) were included. Sensory changes to both the femoral and lateral
      femoral cutaneous nerves occurred in 94% of patients (95% CI: 82%-100%). The
      average volume of ropivacaine 0.2% was 0.53 mL/Kg (SD 0.11 mL/Kg). Echogenic
      landmarks were identified in all patients. Pain scores and opioid consumption
      were generally low. CONCLUSION: A supra-inguinal location for the deposition of
      local anesthetic when performing fascia iliaca nerve block for hip surgery is
      reliable in anesthetizing the femoral and lateral femoral cutaneous nerves and
      should encourage investigation into the clinical efficacy.

PMID- 29030934
TI  - There's no anesthesia like no anesthesia.

PMID- 29030935
TI  - Rapid Response Team activation for pediatric patients on the acute pain service.
AB  - INTRODUCTION: Untreated pain or overly aggressive pain management may lead to
      adverse physiologic consequences and activation of the hospital's Rapid Response
      Team. This study is a quality improvement initiative that attempts to identify
      patient demographics and patterns associated with Rapid Response Team
      consultations for patients on the acute pain service. METHODS: A retrospective
      review of all patients on the acute pain service from February 2011 until June
      2015 was cross-referenced with inpatients requiring consultation from the Rapid
      Response Team. Two independent practitioners reviewed electronic medical records
      to determine which events were likely associated with pain management
      interventions. RESULTS: Over a 4-year period, 4872 patients were admitted to the
      acute pain service of whom 135 unique patients required Rapid Response Team
      consults. There were 159 unique Rapid Response Team activations among 6538 unique
      acute pain service consults. A subset of 27 pain management-related Rapid
      Response Team consultations was identified. The largest percentage of patients on
      the acute pain service were adolescents aged 12-17 (36%). Compared to this age
      group, the odds of Rapid Response Team activation were higher among infants <1
      year old (odds ratio = 2.85; 95% confidence interval: 1.59, 5.10; P < .001) and
      adults over 18 years (odds ratio = 1.68; 95% confidence interval: 1.01, 2.80; P =
      .046). DISCUSSION: Identifying demographics and etiologies of acute pain service
      patients requiring Rapid Response Team consultations may help to identify
      patients at risk for clinical decompensation.

PMID- 29030937
TI  - Changes in blood volume indicators and dynamic indicators measured with
      transpulmonary ultrasound velocity during blood depletion and repletion in a
      neonatal swine model.
AB  - BACKGROUND: Dynamic indicators such as pulse pressure and stroke volume
      variations can be measured to track changes in preload during hemorrhage, and
      evaluate fluid therapy. However, these dynamic indicators require mechanical
      ventilation, and might be affected by cardiac dysrhythmias and changes in
      vascular tone. Blood volume indicators may offer alternatives for assessing
      changes in volume status. AIMS: The aims of this study were to measure changes in
      blood volume indicators and dynamic indicators during removal of blood in two
      stages and subsequent blood replacement in anesthetized, mechanically ventilated,
      neonatal pigs. METHODS: In eight anesthetized, mechanically ventilated piglets (5
      6 weeks old), cardiac index, stroke volume index, total end-diastolic volume,
      central blood volume, active circulating volume, pulse pressure variation, and
      stroke volume variation were measured during blood removal in two stages (15 mL
      kg-1 each stage) and blood replacement (30 mL kg-1 ). Values after each
      intervention were measured for each parameter. RESULTS: All indicators differed
      from baseline after removal of 15 mL kg-1 of blood, except for stroke volume
      variation. Differences between both stages of hemorrhage were only observed for
      indexed stroke volume, total end-diastolic volume, central blood volume, and
      pulse pressure variation. CONCLUSION: Total end-diastolic volume and central
      blood volume changed during blood depletion and repletion, and differed between
      stages of hemorrhage. These indicators might be useful for assessing volume
      status instead of, or in addition to cardiac index and dynamic indicators.

PMID- 29030938
TI  - Opioid use disorder and misuse: A review of the epidemiology and medical
      implications for pediatric anesthesiologists.
AB  - This educational review presents an overview of opioid use disorder, misuse and
      overdose among adolescents, and the clinical implications for anesthesiologists.
      It provides definitions, discusses the epidemiology worldwide, (focusing on North
      America), and emphasizes the clinical implications of patients with chronic
      opioid exposure, including perioperative pain management, as well as opioid
      overdose and prolonged use of opioids after acute exposure. In the USA, opioid
      use disorder and negative outcomes related to opioids rose dramatically from 1999
      2010; concomitantly heroin use and fatal overdoses have increased as heroin use
      is associated with the disordered use of licit opioids. Among adolescents and
      young adults, opioid use disorder is significant, with continued increases in
      disordered use specifically among young adults. Acute opioid intoxication may
      have multiple medical implications in addition to respiratory depression, and
      children are susceptible to acute intoxication via accidental ingestion of
      prescription opioids. Novel opioid formulations, such as acetyl fentanyl, with
      unpredictable pharmacology may also be present in acute intoxication.
      Chronically, opioid use presents challenges for safe and adequate pain
      management, in the presence of opioid-induced hyperalgesia and differential
      tolerance as well as mental health issues including depression and anxiety.
      Predictors of prolonged opioid use in adolescents and adults after surgery is an
      area of ongoing research. Young patients encountered by pediatric
      anesthesiologists may be involved in diversion and disordered use of opioids.
      Increased awareness among anesthesiologists is important, as perioperative
      discussions often provide an opportunity to detect at risk patients.

PMID- 29030939
TI  - Cold shocks of Anammox biofilm stimulate nitrogen removal at low temperatures.
AB  - The adaptation of Anammox (ANaerobic AMMonium OXidation) to low temperatures (10
      15 degrees C) is crucial for sustaining energy-efficient nitrogen removal from
      the mainstream of municipal wastewater. But, current adaptation methods take
      months or even years. To speed up the adaption of Anammox to low temperatures,
      this study describes a new approach: exposing Anammox microorganisms to an abrupt
      temporary reduction of temperature, i.e., cold shock. Anammox biomass in a moving
      bed biofilm reactor was subjected to three consecutive cold shocks (reduction
      from 24 +/- 2 to 5.0 +/- 0.2 degrees C), each taking eight hours. Before the cold
      shocks, Anammox activity determined in ex situ tests using the temperature range
      of 12.5-19.5 degrees C was 0.005-0.015 kg-N kg-VSS-1 day-1 . Cold shocks
      increased the activity of Anammox at 10 degrees C to 0.054 kg-N kg-VSS-1 day-1
      after the third shock, which is similar to the highest activities obtained for
      cold-enriched or adapted Anammox reported in the literature (0.080 kg-N kg-VSS-1
      day-1 ). Fluorescence in situ hybridization analysis showed that Ca. Brocadia
      fulgida was the dominant species. Thus, cold shocks are an intriguing new
      strategy for the adaptation of Anammox to low temperature. (c) 2017 American
      Institute of Chemical Engineers Biotechnol. Prog., 34:277-281, 2018.

PMID- 29030940
TI  - Analysis of red blood cell parameters by Talbot-projected fringes.
AB  - Red blood cell (RBC) anomalies are significant symptoms for identification of
      health disorders and several blood diseases, which involve the modification of
      the parameters and biophysical characteristics of such cells. The aim of this
      study is to measure the three-dimensional phase information of healthy RBCs and
      their parameters, such as cell diameter, thickness, and hemoglobin (Hb) content,
      using Talbot-projected fringes. The Talbot image of linear grating is projected
      onto an RBC slide. The deformed grating lines due to the shape and refractive
      index of RBCs are recorded by a CCD camera through a 20* microscope objective.
      Hilbert transform is used to extract the phase image from the deformed projected
      grating lines. Experimentally calculated values of diameter (8.2  MUm), thickness
      (2.7  MUm), and Hb content (28.7  pg/cell) are well within the limits available
      in the literature. The proposed system is robust and user-friendly and performs
      the imaging of RBCs with high axial and lateral resolution (2.19  MUm).

PMID- 29030941
TI  - Spatiotemporal image correlation analysis of blood flow in branched vessel
      networks of zebrafish embryos.
AB  - Ramification of blood circulation is relevant in a number of physiological and
      pathological conditions. The oxygen exchange occurs largely in the capillary bed,
      and the cancer progression is closely linked to the angiogenesis around the tumor
      mass. Optical microscopy has made impressive improvements in in vivo imaging and
      dynamic studies based on correlation analysis of time stacks of images. Here, we
      develop and test advanced methods that allow mapping the flow fields in branched
      vessel networks at the resolution of 10 to 20  MUm. The methods, based on the
      application of spatiotemporal image correlation spectroscopy and its extension to
      cross-correlation analysis, are applied here to the case of early stage embryos
      of zebrafish.

PMID- 29030942
TI  - Toward jet injection by continuous-wave laser cavitation.
AB  - This is a study motivated by the need to develop a needle-free device for
      eliminating major global healthcare problems caused by needles. The generation of
      liquid jets by means of a continuous-wave laser, focused into a light absorbing
      solution, was studied with the aim of developing a portable and affordable jet
      injector. We designed and fabricated glass microfluidic devices, which consist of
      a chamber where thermocavitation is created and a tapered channel. The growth of
      a vapor bubble displaces and expels the liquid through the channel as a fast
      traveling jet. Different parameters were varied with the purpose of increasing
      the jet velocity. The velocity increases with smaller channel diameters and taper
      ratios, whereas larger chambers significantly reduce the jet speed. It was found
      that the initial position of the liquid-air meniscus interface and its dynamics
      contribute to increased jet velocities. A maximum velocity of 94+/-3  m/s for a
      channel diameter of D=120  MUm, taper ratio n=0.25, and chamber length E=200  MUm
      was achieved. Finally, agarose gel-based skin phantoms were used to demonstrate
      the potential of our devices to penetrate the skin. The maximum penetration depth
      achieved was ~1  mm, which is sufficient to penetrate the stratum corneum and for
      most medical applications. A meta-analysis shows that larger injection volumes
      will be required as a next step to medical relevance for laser-induced jet
      injection techniques in general.

PMID- 29030943
TI  - Noncontact holographic detection for photoacoustic tomography.
AB  - A holographic method for high-speed, noncontact photoacoustic tomography is
      introduced and evaluated. Relative changes of the object's topography, induced by
      the impact of thermoelastic pressure waves, were determined at nanometer
      sensitivity without physical contact. The object's surface was illuminated with
      nanosecond laser pulses and imaged with a high-speed CMOS camera. From two
      interferograms measured before and after excitation of the acoustic wave, surface
      displacement was calculated and then used as the basis for a tomographic
      reconstruction of the initial pressure caused by optical absorption. The
      holographic detection scheme enables variable sampling rates of the photoacoustic
      signal of up to 50 MHz. The total acquisition times for complete volumes with 230
      MVoxel is far below 1 s. Measurements of silicone and porcine skin tissue
      phantoms with embedded artificial absorbers, which served as a model for human
      subcutaneous vascular networks, were possible. Three-dimensional reconstructions
      of the absorbing structures show details with a diameter of 310  MUm up to a
      depth of 2.5 mm. Theoretical limitations and the experimental sensitivity, as
      well as the potential for in vivo imaging depending on the detection repetition
      rate, are analyzed and discussed.

PMID- 29030944
TI  - Noninvasive detection of nasopharyngeal carcinoma based on saliva proteins using
      surface-enhanced Raman spectroscopy.
AB  - The present study evaluated the capability of saliva analysis combining membrane
      protein purification with surface-enhanced Raman spectroscopy (SERS) for
      noninvasive detection of nasopharyngeal carcinoma (NPC). A rapid and convenient
      protein purification method based on cellulose acetate membrane was developed. A
      total of 659 high-quality SERS spectra were acquired from purified proteins
      extracted from the saliva samples of 170 patients with pathologically confirmed
      NPC and 71 healthy volunteers. Spectral analysis of those saliva protein SERS
      spectra revealed specific changes in some biochemical compositions, which were
      possibly associated with NPC transformation. Furthermore, principal component
      analysis combined with linear discriminant analysis (PCA-LDA) was utilized to
      analyze and classify the saliva protein SERS spectra from NPC and healthy
      subjects. Diagnostic sensitivity of 70.7%, specificity of 70.3%, and diagnostic
      accuracy of 70.5% could be achieved by PCA-LDA for NPC identification. These
      results show that this assay based on saliva protein SERS analysis holds
      promising potential for developing a rapid, noninvasive, and convenient clinical
      tool for NPC screening.

PMID- 29030945
TI  - Adenine-induced chronic kidney disease in rats.
AB  - Many animal models have been developed to study the causes and treatments of
      chronic kidney disease (CKD) in humans, an insidious disease resulting from
      kidney injury and characterized by persistent functional decline for more than 3
      months, with or without evidence of structural deficit. The eventual outcome of
      CKD may be end-stage kidney disease (ESKD), where patients need dialysis or
      transplantation to survive. Cardiovascular disease is accelerated in patients
      with CKD and contributes to increased mortality, with the relationship between
      CKD and cardiovascular disease being bi-directional. Most animal models do not
      mimic the complexity of the human disease as many do not develop CKD-associated
      cardiovascular disease. The adenine diet model of CKD in rodents is an exception.
      The original adenine diet model produced rapid-onset kidney disease with
      extensive tubulointerstitial fibrosis, tubular atrophy, crystal formation and
      marked vessel calcification. Since then, lower adenine intake in rats has been
      found to induce slowly progressive kidney damage and cardiovascular disease.
      These chronic adenine diet models allow the characterization of relatively stable
      kidney and cardiovascular disease, similar to CKD in humans. In addition,
      interventions for reversal can be tested. Here the key features of the adenine
      diet model of CKD are noted, along with some limitations of other available
      models. In summary, the data presented here support the use of chronic low-dose
      adenine diet in rats as an easy and effective model for understanding human CKD,
      especially the links with cardiovascular disease, and developing potential
      therapeutic interventions.

PMID- 29030946
TI  - Excrescent tumor on the left sole in a middle-aged man.

PMID- 29030947
TI  - Identification of the novel HLA-B*57:91 allele, by next-generation sequencing in
      a Spanish individual.
AB  - HLA-B*57:91 differs from HLA-B*57:01:01 by a single nucleotide substitution
      resulting in an amino acid change.

PMID- 29030948
TI  - Brief history and user's guide to the Australian National Disability Insurance
      Scheme.

PMID- 29030949
TI  - microRNA expression in the neural retina: Focus on Muller glia.
AB  - The neural retina hosts a unique specialized type of macroglial cell that not
      only preserves retinal homeostasis, function, and integrity but also may serve as
      a source of new neurons during regenerative processes: the Muller cell. Precise
      microRNA-driven mechanisms of gene regulation impel and direct the processes of
      Muller glia lineage acquisition from retinal progenitors during development, the
      triggering of their response to retinal degeneration and, in some cases, Muller
      cell reprogramming and regenerative events. In this review we survey the recent
      reports describing, through functional assays, the regulatory role of microRNAs
      in Muller cell physiology, differentiation potential, and retinal pathology. We
      discuss also the evidence based on expression analysis that points out the
      relevance of a Muller glia-specific microRNA signature that would orchestrate
      these processes.

PMID- 29030950
TI  - Description of four new HLA alleles in the Finnish population: A*03:283N,
      A*68:167, C*03:327, C*03:361.
AB  - New HLA alleles found in the Finnish population: A*03:283N, A*68:167, C*03:327
      and C*03:361.

PMID- 29030952
TI  - The novel allele, HLA-A*31:108, identified by sequence-based typing in a Chinese
      individual.

PMID- 29030951
TI  - Timeliness of Breast Cancer Treatment Within The Alaska Tribal Health System.
AB  - PURPOSE: This study examined the time from breast cancer diagnosis to initiation
      of treatment among Alaska Native (AN) women. We evaluated the impact of age,
      cancer stage, and rural/urban residence at diagnosis. METHODS: We evaluated
      characteristics of women recorded in the Alaska Native Tumor Registry who
      received a first diagnosis of breast cancer between 2009 and 2013. Median time
      from diagnosis to treatment was assessed. Associations of demographic and
      clinical characteristics with timely initiation of treatment were evaluated using
      logistic regression and Cox proportional hazards models. RESULTS: Two hundred
      seventy-eight (278) AN women were diagnosed with invasive breast cancer in years
      2009-2013. Mean age at diagnosis was 56.8 years (SD = 13.0). The median time from
      diagnosis to initiation of treatment was 23 days (P < .05) with most (94.6%, n =
      263) meeting the <=60-day guideline target. Time to treatment was not associated
      with rural/urban residence, age, or stage at cancer diagnosis. CONCLUSION: These
      findings indicate that most AN women diagnosed with breast cancer within the AN
      Tribal Health System receive timely treatment after diagnosis.

PMID- 29030953
TI  - Anti-desmoglein 1 IgG/IgA pemphigus associated with thymoma.

PMID- 29030954
TI  - An international investigation into AB plasma administration in hospitals: how
      many AB plasma units were infused? The HABSWIN study.
AB  - BACKGROUND: Typical practice is to transfuse group-specific plasma units;
      however, there are situations where group AB plasma (universal donor) is issued
      to group A, B, or O recipients. If demand for group AB plasma exceeds
      collections, there is potential for shortage. This project explored the patterns
      of group AB plasma utilization at hospitals around the world. STUDY DESIGN AND
      METHODS: The study had two phases: a survey that inquired about hospital group AB
      plasma inventory, policies, and transfusion practices and a retrospective review
      of 2014 calendar year data where participants submitted information on plasma
      disposition including ABO group of unit and recipient, transfusion location, and
      select indications. Recruitment occurred through snowball sampling. Descriptive
      analyses were performed. RESULTS: Survey data were received from 25 centers
      across 10 countries; of those, 15 participants contributed to the data collection
      component. These 15 centers transfused a total of 43,369 AB plasma units during
      the study period. Only 1496 of 5541 (27%) group AB plasma units were transfused
      to group AB recipients. Transfusion policies, practices, and patterns were
      variable across sites. CONCLUSION: Group AB plasma units are frequently
      transfused to non-AB recipients. Whether transfusing 73% of group AB plasma units
      to non-AB recipients is the ideal inventory management strategy remains to be
      determined.

PMID- 29030955
TI  - Vertically Aligned Co9 S8 Nanotube Arrays onto Graphene Papers as High
      Performance Flexible Electrodes for Supercapacitors.
AB  - Paper-like electrodes are emerging as a new category of advanced electrodes for
      flexible supercapacitors (SCs). Graphene, a promising two-dimensional material
      with high conductivity, can be easily processed into papers. Here, we report a
      rational design of flexible architecture with Co9 S8 nanotube arrays (NAs) grown
      onto graphene paper (GP) via a facile two-step hydrothermal method. When employed
      as flexible free-standing electrode for SCs, the proposed architectured Co9 S8
      /GPs exhibits superior electrochemical performance with ultrahigh capacitance and
      outstanding rate capability (469 F g-1 at 10 A g-1 ). These results demonstrate
      that the new nanostructured Co9 S8 /GPs can be potentially applied in high
      performance flexible supercapacitors.

PMID- 29030957
TI  - Mollusc shells as metagenomic archives: The true treasure is the chest itself.
AB  - Mollusc shells, beyond the treasure of information inherently conveyed through
      their morphology and chemical composition also have the capacity to preserve DNA
      sequences over the long term in their inner structure. This has been clearly
      demonstrated for the first time in the study published in this issue of Molecular
      Ecology Resources by Der Sarkissian et al. (). With a methodology specifically
      dedicated to ancient DNA and solid matrices, the authors were able to
      successfully extract and amplify DNA from marine shells spanning the last 7,000
      years. Furthermore, using metagenomic analyses, they could identify important
      factors affecting DNA recovery. Using reference genomes and sequences in a
      targeted approach to assign high-throughput sequencing reads, the authors
      revealed both the presence of endogenous mollusc DNA and a potent pathogen of
      Manilla clam. Collectively, the results presented in this study open extremely
      promising research avenues, from palaeogenomics and evolutionary biology to
      ecological genomics at population and community levels, as well as the
      opportunity to fine-tune diagnostic tools for conservation and aquaculture
      purposes. Last but not least, this study also offers exciting perspectives in
      epigenomics and the evolution of regulatory processes in the context of
      adaptation to global change. It can be easily expected that the approach
      developed by Der Sarkissian et al. () will be pursued and extensively
      investigated in the near future by the scientific community interested in these
      issues.

PMID- 29030956
TI  - Spatial transcriptomes within the Pseudomonas aeruginosa biofilm architecture.
AB  - Bacterial cooperative associations and dynamics in biofilm microenvironments are
      of special interest in recent years. Knowledge of localized gene-expression and
      corresponding bacterial behaviors within the biofilm architecture at a global
      scale has been limited, due to a lack of robust technology to study limited
      number of cells in stratified layers of biofilms. With our recent pioneering
      developments in single bacterial cell transcriptomic analysis technology, we
      generated herein an unprecedented spatial transcriptome map of the mature in
      vitro Pseudomonas aeruginosa biofilm model, revealing contemporaneous yet altered
      bacterial behaviors at different layers within the biofilm architecture (i.e.,
      surface, middle and interior of the biofilm). Many genes encoding unknown
      functions were highly expressed at the biofilm-solid interphase, exposing a
      critical gap in the knowledge of their activities that may be unique to this
      interior niche. Several genes of unknown functions are critical for biofilm
      formation. The in vivo importance of these unknown proteins was validated in
      invertebrate (fruit fly) and vertebrate (mouse) models. We envisage the future
      value of this report to the community, in aiding the further pathophysiological
      understanding of P. aeruginosa biofilms. Our approach will open doors to the
      study of bacterial functional genomics of different species in numerous settings.

PMID- 29030958
TI  - Association of MEOX2 polymorphism with nonsyndromic cleft palate only in a
      Vietnamese population.
AB  - To evaluate the association between the single nucleotide polymorphism (SNP)
      rs227493 in the MEOX2 gene and nonsyndromic cleft palate only, this research was
      conducted as a case-control study by comparing a nonsyndromic cleft palate only
      group with an independent, healthy, and unaffected control group who were both
      examined by specialists. Based on clinical examination and medical records, we
      analyzed a total of 570 DNA samples, including 277 cases and 293 controls, which
      were extracted from dry blood spot samples collected from both the Odonto and
      Maxillofacial Hospital in Ho Chi Minh City and Nguyen Dinh Chieu Hospital in Ben
      Tre province, respectively. The standard procedures of genotyping the specific
      SNP (rs2237493) for MEOX2 were performed on a StepOne Realtime PCR system with
      TaqMan SNP Genotyping Assays. Significant statistical differences were observed
      in allelic frequencies (allele T and allele G) between the non-syndromic cleft
      palate only and control groups in female subjects, with an allelic odds ratio of
      1.455 (95% confidence interval: 1.026-2.064) and P < 0.05. These study findings
      suggest that nonsyndromic isolated cleft palate might be influenced by variation
      of MEOX2, especially SNP rs2237493 in Vietnamese females.

PMID- 29030959
TI  - iPSC-Derived Vascular Cell Spheroids as Building Blocks for Scaffold-Free
      Biofabrication.
AB  - Recently a protocol is established to obtain large quantities of human induced
      pluripotent stem cells (iPSC)-derived endothelial progenitors, called endothelial
      colony forming cells (ECFC), and of candidate smooth-muscle forming cells (SMFC).
      Here, the suitability for assembling in spheroids, and in larger 3D cell
      constructs is tested. iPSC-derived ECFC and SMFC are labeled with tdTomato and
      eGFP, respectively. Spheroids are formed in ultra-low adhesive wells, and their
      dynamic proprieties are studied by time-lapse microscopy, or by confocal
      microscopy. Spheroids are also tested for fusion ability either in the wells, or
      assembled on the Regenova 3D bioprinter which laces them in stainless steel micro
      needles (the "Kenzan" method). It is found that both ECFC and SMFC formed
      spheroids in about 24 h. Fluorescence monitoring indicated a continuous
      compaction of ECFC spheroids, but stabilization in those prepared from SMFC. In
      mixed spheroids, the cell distribution changed continuously, with ECFC relocating
      to the core, and showing pre-vascular organization. All spheroids have the
      ability of in-well fusion, but only those containing SMFC are robust enough to
      sustain assembling in tubular structures. In these constructs a layered
      distribution of alpha smooth muscle actin-positive cells and extracellular matrix
      deposition is found. In conclusion, iPSC-derived vascular cell spheroids
      represent a promising new cellular material for scaffold-free biofabrication.

PMID- 29030960
TI  - Cell-free DNA noninvasive prenatal screening for aneuploidy versus conventional
      screening: A systematic review of economic evaluations.
AB  - Although noninvasive prenatal testing (NIPT) for aneuploidies using cell-free
      fetal DNA in maternal blood has been reported to have a high accuracy, only
      little evidence about its cost-effectiveness is available. We systematically
      reviewed and assessed quality of economic evaluation studies published between
      January 1, 2009 and January 1, 2016 where NIPT was compared to the current
      screening practices consisting of biochemical markers with or without nuchal
      translucency (NT) and/or maternal age. We included 16 studies and we found that,
      at current level of NIPT prices, contingent NIPT provide the best value for
      money, especially for publicly funded screening programs. NIPT as first-line test
      was found not cost-effective in the majority of studies. The NIPT unit cost, the
      risk cut-offs for current screening practice, the screening uptake rates (first-
      and second-line screening) as well as the costs and uptake rates of invasive
      diagnostic screening were the most common uncertain variables. The overall
      quality of included studies was fair. Considering a possible drop in prices and
      an ongoing NIPT expansion to include other chromosomes abnormalities other than
      T21, T18, T13 and sex chromosomes aneuploidies, future research are needed to
      examine the potential cost-effectiveness of implementing NIPT as first-line test.

PMID- 29030961
TI  - Overproduction of MCL-PHA with high 3-hydroxydecanoate Content.
AB  - Methods of producing medium-chain-length poly-3-hydroxyalkanoate (mcl-PHA) with
      high content of the dominant subunit, 3-hydroxydecanoate (HD), were examined with
      an emphasis on a high yield of polymer from decanoic acid. High HD content was
      achieved by using a beta-oxidation knockout mutant of Pseudomonas putida KT2440
      (designated as P. putida DBA-F1) or by inhibiting beta-oxidation with addition of
      acrylic acid (Aa) to wild type P. putida KT2440 in carbon-limited, fed-batch
      fermentations. At a substrate feed ratio of decanoic acid and acetic acid to
      glucose (DAA:G) of 6:4 g/g, P. putida DBA-F1 accumulated significantly higher HD
      (97 mol%), but much lower biomass (8.5 g/L) and PHA (42% of dry biomass) than the
      wild type. Both biomass and PHA concentrations were improved by decreasing the
      ratio of DAA:G to 4:6. Moreover, when the substrate feed ratio was further
      decreased to 2:8, 18 g/L biomass containing 59% mcl-PHA consisting of 100 mol% HD
      was achieved. The yield of PHA from decanoic acid was 1.24 (g/g) indicating that
      de novo synthesis had contributed to production. Yeast extract and tryptone (YET)
      addition allowed the mutant strain to accumulate 74% mcl-PHA by weight with 97
      mol% HD at a production rate of 0.41 g/L/hr, at least twice that of published
      data for any beta-oxidation knock-out mutant. Higher biomass concentration was
      achieved with Aa inhibition of beta-oxidation in the wild type but the HD content
      (84 mol%) was less than that of the mutant. A carbon balance showed a marked
      increase in supernantant organic carbon for the mutant indicating overflow
      metabolism. Increasing the dominant monomer content (HD) greatly increased
      melting point, crystallinity, and rate of crystallization.

PMID- 29030962
TI  - LncRNA DGCR5 promotes lung adenocarcinoma (LUAD) progression via inhibiting hsa
      mir-22-3p.
AB  - Long non-coding RNAs (lncRNAs) serve critical roles in the pathogenesis of
      various cancers, including lung adenocarcinoma (LUAD). Herein, in this study, we
      aimed to investigate the biological and clinical significance of lncRNA DiGeorge
      syndrome critical region gene 5 (DGCR5) in LUAD. It was observed that DGCR5 was
      upregulated in LUAD tissues and LUAD cell lines. Inhibition of DGCR5 can prevent
      LUAD progression via playing anti-apoptosis roles. Both mRNA expression and
      protein levels of BCL-2 were increased by DGCR5 downregulation while reversely
      BAX was increased. Additionally, a novel microRNA target of DGCR5, hsa-mir-22-3p
      was identified through bioinformatics search and confirmed by dual-luciferase
      reporter system. Gain and loss-of-function studies were performed to verify
      whether DGCR5 exerts its biological functions through regulating hsa-mir-22-3p in
      vitro. Overexpression of DGCR5 was able to reverse the tumor inhibitory effect of
      hsa-mir-22-3p mimics. Furthermore, in vivo tests tumor xenografts were
      established to detect the function of DGCR5 in LUAD tumorigenesis. Downregulated
      DGCR5 expression was greatly associated with smaller tumor size, implying a
      favorable prognosis of LUAD patients. Taken these together, DGCR5 could be
      considered as a prognostic biomarker and therapeutic target in LUAD diagnosis and
      treatment.

PMID- 29030963
TI  - Estrogen regulates stemness and senescence of bone marrow stromal cells to
      prevent osteoporosis via ERbeta-SATB2 pathway.
AB  - Decline of pluripotency in bone marrow stromal cells (BMSCs) associated with
      estrogen deficiency leads to a bone formation defect in osteoporosis. Special AT
      rich sequence binding protein 2 (SATB2) is crucial for maintaining stemness and
      osteogenic differentiation of BMSCs. However, whether SATB2 is involved in
      estrogen-deficiency associated-osteoporosis is largely unknown. In this study, we
      found that estrogen mediated pluripotency and senescence of BMSCs, primarily
      through estrogen receptor beta (ERbeta). BMSCs from the OVX rats displayed
      increased senescence and weaker SATB2 expression, stemness, and osteogenic
      differentiation, while estrogen could rescue these phenotypes. Inhibition of
      ERbeta or ERalpha confirmed that SATB2 was associated with ERbeta in estrogen
      mediated pluripotency and senescence of BMSCs. Furthermore, estrogen mediated the
      upregulation of SATB2 through the induction of ERbeta binding to estrogen
      response elements (ERE) located at -488 of the SATB2 gene. SATB2 overexpression
      alleviated senescence and enhanced stemness and osteogenic differentiation of OVX
      BMSCs. SATB2-modified BMSCs transplantation could prevent trabecular bone loss in
      an ovariectomized rat model. Collectively, our study revealed the role of SATB2
      in stemness, senescence, and osteogenesis of OVX-BMSCs. These results indicate
      that estrogen prevents osteoporosis by promoting stemness and osteogenesis, and
      inhibiting senescence of BMSCs through an ERbeta-SATB2 pathway. Therefore, SATB2
      is a novel anti-osteoporosis target gene.

PMID- 29030964
TI  - Transcription factor HMG box-containing protein 1 (HBP1) modulates mitotic clonal
      expansion (MCE) during adipocyte differentiation.
AB  - Transcription factor HMG box-containing protein 1 (HBP1) has been found to be up
      regulated in rat adipose tissue and differentiated preadipocyte; however, how
      HBP1 is involved in adipocyte formation remains unclear. In the present study, we
      demonstrated that under a standard differentiation protocol HBP1 expression
      fluctuates with down-regulation in the mitotic clonal expansion (MCE) stage
      followed by up-regulation in the terminal differentiation stage in both 3T3-L1
      and MEF cell models. Also, HBP1 knockdown accelerated cell cycle progression in
      the MCE stage, but it impaired final adipogenesis. To gain further insight into
      the role of HBP1 in the MCE stage, we found that the HBP1 expression pattern is
      reciprocal to that of C/EBPbeta, and ectopic expression of HBP1suppresses
      C/EBPbeta expression. These data indicate that HBP1 functions as a negative
      regulator of MCE. In contrast, when HBP1 expression was gradually elevated along
      with a concomitant induction of C/EBPalpha at the end of the MCE, HBP1 knockdown
      leads to a significant reduction of C/EBPalpha expression, suggesting that HBP1
      mediated C/EBPalpha expression may be needed for the termination of the cell
      cycle at the end of MCE for terminal differentiation. All told, our findings show
      that HBP1 is a key transcription factor in the already complicated regulatory
      cascade during adipocyte differentiation.

PMID- 29030965
TI  - Fear affects parental care, which predicts juvenile survival and exacerbates the
      total cost of fear on demography.
AB  - Fear itself (perceived predation risk) can affect wildlife demography, but the
      cumulative impact of fear on population dynamics is not well understood. Parental
      care is arguably what most distinguishes birds and mammals from other taxa, yet
      only one experiment on wildlife has tested fear effects on parental food
      provisioning and the repercussions this has for the survival of dependent
      offspring, and only during early-stage care. We tested the effect of fear on late
      stage parental care of mobile dependent offspring, by locating radio-tagged Song
      Sparrow fledglings and broadcasting predator or non-predator playbacks in their
      vicinity, measuring their parent's behavior and their own, and tracking the
      offspring's survival to independence. Fear significantly reduced late-stage
      parental care, and parental fearfulness (as indexed by their reduction in
      provisioning when hearing predators) significantly predicted their offspring's
      condition and survival. Combining results from this experiment with that on early
      stage care, we project that fear itself is powerful enough to reduce late-stage
      survival by 24%, and cumulatively reduce the number of young reaching
      independence by more than half, 53%. Experiments in invertebrate and aquatic
      systems demonstrate that fear is commonly as important as direct killing in
      affecting prey demography, and we suggest focusing more on fear effects and on
      offspring survival will reveal the same for wildlife.

PMID- 29030966
TI  - Metabolic reduction of resazurin; location within the cell for cytotoxicity
      assays.
AB  - Resazurin is widely used as a metabolic indicator for living cells, however,
      there has been considerable debate in the literature with regards to the specific
      location in the cell where the non-fluorescent resazurin is reduced to the
      strongly fluorescent resorufin. This lack of clarity about the reduction site
      makes the use of resazurin reduction data in cytotoxicity studies difficult to
      interpret. In this study, E. faecalis, a Gram-positive and facultative anaerobic
      bacterial strain, and the most toxic chlorophenol, pentachlorophenol (PCP), were
      chosen as models for an anaerobe and toxicant, respectively. By studying the
      kinetics of resazurin reduction by E. faecalis after different treatments (cell
      disruption, bacterial filtration, and pre-exposure to toxicant), we confirmed
      that resazurin reduction to resorufin by live Gram-positive and facultative
      anaerobic bacterial cells can only happen intracellularly under anaerobic
      conditions, while resorufin reduction to dihydroresorufin can happen both
      intracellularly and extracellularly. Based on the understanding of these
      fundamental mechanisms, we suggest that resazurin reduction can be used as a
      quick bioassay for measuring cytotoxicity.

PMID- 29030967
TI  - Preservation of Ceriporiopsis subvermispora and Lentinula edodes treated wheat
      straw under anaerobic conditions.
AB  - BACKGROUND: No attention has been paid so far to the preservation of fungal
      treated lignocellulose for longer periods. In the present study, we treated wheat
      straw (WS) with the white-rot fungi Ceriporiopsis subvermispora and Lentinula
      edodes for 8 weeks and assessed changes in pH, chemical composition and in vitro
      gas production (IVGP) weekly. Fungal-treated WS was also stored for 64 days 'as
      is', with the addition of lactic acid bacteria (LAB) or with a combination of LAB
      and molasses in airtight glass jars mimicking ensiling conditions. RESULTS: Both
      fungi significantly reduced the lignin and hemicellulose content of WS, and
      increased the cellulose content. The IVGP increased with increasing time of
      incubation, indicating the increase in digestibility. Both fungi lowered the pH
      of WS under 4.3, which guarantees an initial and stable low pH during anaerobic
      storage. Minor changes in fibre composition and IVGP were observed for stored L.
      edodes treated WS, whereas no change occurred for C. subvermispora. CONCLUSION:
      It is possible to conserve C. subvermispora and L. edodes treated straw under
      anaerobic condition without additives up to 64 days. This finding is important
      for practical application to supply fungi-treated feed to ruminant animals for a
      prolonged period. (c) 2017 The Authors. Journal of The Science of Food and
      Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical
      Industry.

PMID- 29030968
TI  - Mycoflora assessment, growth and toxigenic features of patulin-producers in
      kiwifruit in China.
AB  - BACKGROUND: Fungal development in agricultural products may cause mycotoxin
      contamination, which is a significant threat to food safety. Patulin (PAT) and
      PAT-producer contamination has been established as a worldwide problem. The
      present study aimed to investigate the mycoflora and PAT-producers present in
      kiwifruits and environmental samples collected from orchards and processing
      plants in Shaanxi Province, China. RESULTS: Variations in mycoflora were observed
      in different samples, with penicillia and aspergilli as the predominant genera.
      Approximately 42.86% of dropped fruits were contaminated with PAT-producers,
      which harbored the 6-methylsalicylic acid synthase and the isoepoxydon
      dehydrogenase genes that are involved in PAT biosynthesis. The growth of
      Penicillium expansum, Penicillium griseofulvum and Penicillium paneum in kiwi
      puree agar (KPA) medium and kiwi juice well fitted the modified Gompertz and
      Baranyi and Roberts models (R2 >= 0.95). A significant positive correlation
      between colony diameter and PAT content in KPA medium of P. expansum and P.
      griseofulvum was observed (P < 0.05). CONCLUSIONS: The present study analyzed the
      mycofloral composition and the potential risk for PAT and PAT-producer
      contamination in kiwifruit, which may be utilized in the establishment of proper
      management practices in the kiwifruit industry. (c) 2017 Society of Chemical
      Industry.

PMID- 29030970
TI  - Annexin A1, Annexin A2, and Dyrk 1B are upregulated during GAS1-induced cell
      cycle arrest.
AB  - GAS1 is a pleiotropic protein that has been investigated because of its ability
      to induce cell proliferation, cell arrest, and apoptosis, depending on the
      cellular or the physiological context in which it is expressed. At this point, we
      have information about the molecular mechanisms by which GAS1 induces
      proliferation and apoptosis; but very few studies have been focused on
      elucidating the mechanisms by which GAS1 induces cell arrest. With the aim of
      expanding our knowledge on this subject, we first focused our research on finding
      proteins that were preferentially expressed in cells arrested by serum
      deprivation. By using a proteomics approach and mass spectrometry analysis, we
      identified 17 proteins in the 2-DE protein profile of serum deprived NIH3T3
      cells. Among them, Annexin A1 (Anxa1), Annexin A2 (Anxa2), dual specificity
      tyrosine-phosphorylation-regulated kinase 1B (Dyrk1B), and Eukaryotic translation
      initiation factor 3, F (eIf3f) were upregulated at transcriptional the level in
      proliferative NIH3T3 cells. Moreover, we demonstrated that Anxa1, Anxa2, and
      Dyrk1b are upregulated at both the transcriptional and translational levels by
      the overexpression of GAS1. Thus, our results suggest that the upregulation of
      Anxa1, Anxa2, and Dyrk1b could be related to the ability of GAS1 to induce cell
      arrest and maintain cell viability. Finally, we provided further evidence showing
      that GAS1 through Dyrk 1B leads not only to the arrest of NIH3T3 cells but also
      maintains cell viability.

PMID- 29030969
TI  - Adropin preserves the blood-brain barrier through a Notch1/Hes1 pathway after
      intracerebral hemorrhage in mice.
AB  - Adropin is expressed in the CNS and plays a crucial role in the development of
      stroke. However, little is currently known about the effects of adropin on the
      blood-brain barrier (BBB) function after intracerebral hemorrhage (ICH). In this
      study, the role of adropin in collagenase-induced ICH was investigated in mice.
      At 1-h post-ICH, mice were administered with recombinant human adropin by
      intranasal. Brain water +content, BBB permeability, and neurological function
      were measured at different time intervals. Proteins were quantified using western
      blot analysis, and the localizations of adropin and Notch1 were visualized via
      immunofluorescence staining. It is shown that adropin reduced brain water content
      and improved neurological functions. Adropin preserved the functionality of BBB
      by increasing N-cadherin expression and reducing extravasation of albumin.
      Moreover, in vivo knockdown of Notch1 and Hes1 both abolished the protective
      effects of adropin. Taken together, our data demonstrate that adropin constitutes
      a potential treatment value for ICH by preserving BBB and improving functional
      outcomes through the Notch1 signaling pathway.

PMID- 29030972
TI  - White clover fractions as protein source for monogastrics: dry matter
      digestibility and protein digestibility-corrected amino acid scores.
AB  - BACKGROUND: The present study aimed to evaluate the use of white clover as an
      alternative protein source for monogastrics. White clover plant and leaves were
      processed using a screw-press resulting in a solid pulp and a juice from which
      protein was acid-precipitated. The chemical composition of all fractions was
      determined and digestibility of dry matter (DM) and protein was assessed in an
      experiment with growing rats. RESULTS: Protein concentrates were produced with
      crude protein (CP) contents of 451 g kg-1 and 530 g kg-1 DM for white clover
      plant and leaves, respectively, and a pulp with CP contents of 313 and 374 g kg-1
      DM from plant and leaves, respectively. The amino acid composition ranged from
      4.72 to 6.49 g per 16 g of nitrogen (N) for lysine, 1.82-2.6 g per 16 g N for
      methionine and cysteine, and 3.66-5.24 g per 16 g N for threonine. True faecal
      digestibility of protein varied from 0.81 to 0.88, whereas DM digestibility was
      in the range 0.72-0.80. Methionine and cysteine were found to be limiting in all
      fractions, regardless of the reference group used. CONCLUSION: A high
      digestibility of white clover protein was found irrespective of the physical
      fractionation. Together with a well-balanced amino acid composition, this makes
      white clover a promising protein source for monogastrics. (c) 2017 Society of
      Chemical Industry.

PMID- 29030973
TI  - Returning to work after laparoscopic myomectomy: a prospective observational
      study.
AB  - INTRODUCTION: Laparoscopic myomectomy offers women many benefits over
      conventional open surgery, including an expedited recovery and return to
      employment. Our study evaluates the time taken for women to return to work after
      laparoscopic myomectomy and identifies factors prolonging recovery to > 8 weeks.
      MATERIAL AND METHODS: We prospectively evaluated 94 women undergoing laparoscopic
      myomectomy by a single surgeon between January 2012 and March 2015. Women had
      standardized preoperative counseling and completed a validated return to work
      questionnaire 3 months postoperatively via telephone, post or in clinic. RESULTS:
      In all, 71/94 (75.5%) women completed the questionnaire. Results were analyzed
      comparing women who returned to work in <= 8 weeks [43/71 (60.6%)] with those who
      returned > 8 weeks postoperatively [28/71 (39.4%)]. A higher proportion of Asian
      and Caucasian women returned to work in <= 8 weeks (24/29) compared with black
      African and Caribbean women (19/42) (p = 0.003). Mean number of fibroids removed
      (2.59 and 5.75, respectively) was the only significantly differing factor between
      the two groups (p = 0.004). There was a significant difference in body mass index
      (BMI) and time to return to normal activity between the <= 8-week and > 8-week
      groups (p = 0.027, p = 0.011, respectively). Logistic regression analysis
      demonstrated that BMI and time to return to normal activity were the only factors
      prolonging recovery to > 8 weeks (p = 0.039, p = 0.015, respectively).
      CONCLUSIONS: Time to return to normal activity and BMI significantly influenced
      the time taken for women to work after laparoscopic myomectomy. Further data
      would support clinicians in counseling women appropriately and optimizing their
      postoperative return to employment.

PMID- 29030971
TI  - Nicotinic acetylcholine receptors in neuropathic and inflammatory pain.
AB  - Nicotinic acetylcholine receptors (nAChRs) are actively being investigated as
      therapeutic targets for the treatment of pain and inflammation, but despite more
      than 30 years of research, there are currently no FDA-approved analgesics that
      are specific for these receptors. Much of the initial research effort focused on
      the alpha4beta2 nAChR subtype, but more recently, additional subtypes have been
      identified as promising new leads and include alpha6beta4, alpha7, and alpha9
      containing nAChRs. This Review will focus on the distribution of these nAChRs in
      the cell types involved in neuropathic pain and inflammation and the activity of
      currently available nicotinic ligands.

PMID- 29030975
TI  - Real-time prediction of pre-cooked Japanese sausage color with different storage
      days using hyperspectral imaging.
AB  - BACKGROUND: Redness can greatly influence the freshness of sausages. A precise,
      rapid and noncontact analytical method or tool is needed to quantify the color.
      Hyperspectral imaging (HSI) is an emerging technique that integrates spectroscopy
      and imaging to obtain the spectral and spatial information simultaneously. In the
      present study, the redness of cooked sausages stored up to 57 days was predicted
      using HSI in tandem with multivariate data analysis. The mean spectra of the
      sausages were extracted from the hyperspectral images. Partial least squares
      regression (PLSR) and forward stepwise multiple regression (FSMR) models were
      used to develop the relavent spectral profiles with the redness of the cooked
      sausages. RESULTS: Ten important wavelengths were selected based on the
      regression coefficient values from the PLSR model. The PLSR model established
      using the full wavelengths presented a good performance, with Rc of 0.934 and a
      root mean square error of calibration of 0.642 (redness ranged between 14.99 and
      21.48). The prediction maps for demonstrating evolution of redness in sausages
      were developed for the first time using R statistics (R Foundation for
      Statistical Computing) and Matlab (MathWorks Inc., Natick, MA, USA). CONCLUSION:
      HSI combined with PLSR and FSMR can be used to quantify and visualize evolution
      of sausage redness under different storage days. (c) 2017 Society of Chemical
      Industry.

PMID- 29030974
TI  - Dopamine Transporter Gene Methylation is Associated with Nucleus Accumbens
      Activation During Reward Processing in Healthy but not Alcohol-Dependent
      Individuals.
AB  - BACKGROUND: Alcohol's reinforcement is mediated by dopamine signaling in the
      ventral striatum, which is modulated by the dopamine transporter (DAT). We
      hypothesized that methylomic variation in the DAT gene (DAT1/SLC6A3) affects DAT
      expression, thus contributing to differences in brain reward circuitry in
      individuals with alcohol dependence (ALC). METHODS: Blood from 45 recently
      detoxified ALC and 45 healthy control (HC) individuals was used to assess DNA
      methylation across 5 functional regions of SLC6A3. Participants completed the
      monetary incentive delay task in a 3-Tesla magnetic resonance imaging (MRI)
      scanner. Employing regression models, we examined effects of SLC6A3 methylation
      on nucleus accumbens (NAc) blood-oxygen-level dependent (BOLD) responses during
      anticipation of high/low reward/loss. RESULTS: Results showed that decreased
      methylation of the promoter region of SLC6A3 predicted NAc activation during high
      loss anticipation (p = 0.028) and low loss anticipation (at trend-level; p =
      0.057) in HC but not in individuals with ALC. Specifically, percentage of
      methylation at 2 CpG sites, located -1,001 and -993 base pairs from the
      transcription start site, accounted for significant variability in NAc activation
      in the HC group during high (ps <= 0.010) and low (ps <= 0.006) loss
      anticipation. There was no effect on reward anticipation. Furthermore, promoter
      methylation was positively associated with age, which replicates previous
      findings. CONCLUSIONS: Our data suggest that methylation in the promoter region
      of SLC6A3 predicts NAc activation during the anticipation of monetary loss in
      HCs. However, this effect was not present in the ALC group, suggesting that
      epigenetic regulation of striatal DAT expression might be disrupted in ALC, which
      may contribute to previously reported differences in sensitivity to reward and
      punishment in this population. Alternatively, it is possible that a similar
      relationship in the ALC group remained undetected possibly due to methodological
      limitations inherent in functional MRI (e.g., poor spatial resolution, low signal
      to-noise ratio) that generally restrict interpretations regarding mechanisms of
      epigenetic factors involved in group differences in BOLD responses. Future
      neuroimaging studies are needed to further elucidate the relationship between
      SLC6A3 methylation and NAc activation in ALC.

PMID- 29030977
TI  - Brenda Roe and Rita Pickler.

PMID- 29030976
TI  - Synergistic effect of HIF-1alpha and FoxO3a trigger cardiomyocyte apoptosis under
      hyperglycemic ischemia condition.
AB  - Cardiomyocyte death is an important pathogenic feature of ischemia and heart
      failure. Through this study, we showed the synergistic role of HIF-1alpha and
      FoxO3a in cardiomyocyte apoptosis subjected to hypoxia plus elevated glucose
      levels. Using gene specific small interfering RNAs (siRNA), semi-quantitative
      reverse transcriptase polymerase chain reaction (RT-PCR), Western blot,
      immunofluorescence, nuclear and cytosolic localization and TUNEL assay
      techniques, we determined that combined function of HIF-1alpha and FoxO3a under
      high glucose plus hypoxia condition lead to enhanced expression of BNIP3 inducing
      cardiomyocyte death. Our results highlighted the importance of the synergistic
      role of HIF-1alpha and FoxO3a in cardiomyocyte death which may add insight into
      therapeutic approaches to pathophysiology associated with ischemic diabetic
      cardiomyopathies.

PMID- 29030979
TI  - Pioglitazone inhibits cancer cell growth through STAT3 inhibition and enhanced
      AIF expression via a PPARgamma-independent pathway.
AB  - Pioglitazone is an anti-diabetic agent that belongs to the thiazolidinedione
      class, which target peroxisome proliferator-activated receptor gamma (PPARgamma),
      a transcription factor in the nuclear receptor family. Different cancer cells
      expressing high levels of PPARgamma and PPARgamma ligands induce cell cycle
      arrest, cell differentiation, and apoptosis. However, the mechanisms underlying
      these processes remain unknown. Here, we investigated the mechanism underlying
      pioglitazone-induced apoptosis in human cancer cells. We showed that at similar
      concentrations, pioglitazone induced death in cancer cells expressing high or low
      levels of PPARgamma. Combined treatment of pioglitazone and GW9662, a PPARgamma
      antagonist, did not rescue this cell death phenotype. Z-VAD-fmk, a pan-caspase
      inhibitor, did not reverse pioglitazone-induced apoptosis in cancer cells
      expressing PPARgamma at high or low levels. Pioglitazone suppressed the
      activation of signal transducers and activator of transcription 3 (STAT3) and
      Survivin expression, and enhanced the apoptosis-inducing factor (AIF) levels in
      these cells. Furthermore, pioglitazone enhanced the cytotoxic effect of cisplatin
      and oxaliplatin by suppressing Survivin and increasing AIF expression. These
      results indicated that pioglitazone induced apoptosis via a PPARgamma-independent
      pathway, thus describing pioglitazone as a potential therapeutic agent for
      controlling the progression of different cancers.

PMID- 29030978
TI  - Types of cell death and apoptotic stages in Chinese Hamster Ovary cells
      distinguished by Raman spectroscopy.
AB  - Cell death is the ultimate cause of productivity loss in bioreactors that are
      used to produce therapeutic proteins. We investigated the ability of Raman
      spectroscopy to detect the onset and types of cell death for Chinese Hamster
      Ovary (CHO) cells-the most widely used cell type for therapeutic protein
      production. Raman spectroscopy was used to compare apoptotic, necrotic,
      autophagic, and control CHO cells. Several specific nucleic acid-, protein-, and
      lipid-associated marker bands within the 650-850 cm-1 spectral region were
      identified that distinguished among cells undergoing different modes of cell
      death; supporting evidence was provided by principal component analysis (PCA) of
      the full spectral data. In addition to comparing the different modes of cell
      death, normal cells were compared to cells sorted at several stages of apoptosis,
      in order to explore the potential for early detection of apoptosis. Different
      stages of apoptosis could be distinguished via Raman spectroscopy, with multiple
      changes observed in nucleic acid peaks at early stages whereas an increase in
      lipid signals was a feature of late apoptosis/secondary necrosis.

PMID- 29030980
TI  - Beneficial Effect of Alcohol Withdrawal on Gut Permeability and Microbial
      Translocation in Patients with Alcohol Use Disorder.
AB  - BACKGROUND: The human intestinal microbiota exerts beneficial or harmful effects
      in several disorders. Many factors, including alcohol consumption, may influence
      its composition and trigger bacterial translocation. Excessive alcohol
      consumption increases gut permeability and translocation of endotoxin into
      peripheral circulation. Although plasma endotoxin concentrations have been
      measured often, quantitative changes following alcohol withdrawal have never been
      described in subjects with alcohol use disorder (AUD). The aim of this study was
      to measure microbial translocation (MT) and gut permeability markers in patients
      with AUD, to compare these markers to healthy controls (HC) and to monitor
      markers during the first 6 weeks of abstinence. METHODS: Sixty-five patients with
      AUD and hospitalized for alcohol withdrawal were included. Epidemiological,
      clinical, biological, and addictological data were gathered. Blood samples were
      collected at baseline, then 3 and 6 weeks after alcohol withdrawal. A hundred
      healthy volunteers were used as controls. Three markers of MT were monitored in
      plasma samples: sCD14 and lipopolysaccharide-binding protein (LBP) were
      quantified using ELISA, and 16S rDNA was quantified using real-time polymerase
      chain reaction. Zonulin and intestinal fatty acid binding protein (I-FABP) blood
      levels were also monitored as indirect markers of gut permeability, using ELISA.
      RESULTS: At baseline, LBP, 16S rDNA, sCD14 and I-FABP markers were significantly
      higher in patients with AUD than in HC. Six weeks after alcohol withdrawal plasma
      levels of sCD14 and LBP decreased significantly. Cannabis consumption and body
      mass index (BMI) before alcohol withdrawal influenced baseline MT levels and the
      decrease in MT markers after 6 weeks. Finally, markers of MT and gut permeability
      did not correlate with each other before and after alcohol withdrawal.
      CONCLUSIONS: Before alcohol withdrawal, MT markers were higher in patients with
      AUD than in HC. After 6 weeks of abstinence, an improvement in MT markers was
      observed. Our data suggest that there is a link between MT, its improvement, BMI,
      and cannabis consumption.

PMID- 29030981
TI  - Mesalazine treatment in organotypic culture of celiac patients: Comparative study
      with gluten free diet.
AB  - Given the central role of gluten in the pathogenesis of celiac disease (CD), a
      strict gluten-free diet (GFD) is the only validated treatment able to restore
      epithelium integrity and eliminate risks of complications. The risk of gluten
      contamination and the persistence of inflammation, even in patients strictly
      adhering to GFD, may render this treatment not always effective claiming the
      necessity of different new solutions. Oxidative and nitrosative stress have been
      indicated to play a pathophysiological role in CD. Mesalazine (5-ASA), a drug
      largely used in inflammatory bowel disease, has potent antinflammatory and
      antioxidant effects. In fact, mesalazine has been shown to decrease in vitro
      gluten induced cytokine response and it has been used in vivo in some refractory
      condition. However, its effect has never compared to that of GFD. The present
      study aimed to address this issue by comparing the ability of mesalazine and GFD
      in treating gluten-induced inflammation and oxidative stress. These effects were
      studied on duodenal mucosa biopsy cultures from newly diagnosed CD patients,
      treated or not in vitro with mesalazine, and CD biopsy cultures from patients on
      gluten-free diet for at least one year; and a cohort of controls constituted by
      healty subjects. On these models, the antioxidant cellular defences, the
      PPARgamma, NF-kB and NOS2 proteins levels were studied. This study shows that
      mesalazine is as effective as GFD in reducing oxidative burst and inducing
      PPARgamma expression; moreover it resulted more effective than GFD in decreasing
      NF-kB and NOS2 to the levels of controls.

PMID- 29030982
TI  - Racial disparities in comorbidity and severe maternal morbidity/mortality in the
      United States: an analysis of temporal trends.
AB  - INTRODUCTION: Severe maternal morbidity and mortality have increased in the USA
      in recent years. This trend has not been consistent across all racial groups. The
      reasons behind this, and the relation between preexisting conditions, pregnancy
      associated disease and severe maternal morbidity/mortality, have not been fully
      explored. MATERIAL AND METHODS: Annual data on delivery hospitalizations between
      1993 and 2012 were obtained from the Nationwide Inpatient Sample (NIS),
      representing a 20% sample of hospital discharges from across the USA. Chi-square
      tests for trend were used to examine temporal patterns in the proportion of
      pregnancies affected by comorbidities as defined by the Obstetric Comorbidity
      Score and were stratified by maternal race. Logistic regression was used to
      determine the impact of temporal increases in comorbidity on severe maternal
      morbidity/mortality. RESULTS: In 1993, 34.3% of pregnancies had a comorbidity
      score of >=1; this significantly increased to 44.1% by 2012 (p < 0.001). Baseline
      differences were observed between all races (Whites 33.7%, Blacks 34.5%,
      Hispanics 28.0%, Asian/Pacific Islanders 28.1%). Although significant increases
      were observed for all races, the relative rate of change was lowest for Whites
      (26.1% increase) and highest for Asian/Pacific Islanders (49.1% increase). The
      odds of severe maternal morbidity/mortality have steadily increased over time;
      however, adjustment for Obstetric Comorbidity Score significantly attenuates this
      correlation. CONCLUSION: The rate of both preexisting comorbidities and pregnancy
      associated disease is increasing in pregnant women in the USA and varies
      substantially by race. These trends provide valuable insight into the increasing
      complexity of pregnancy in the USA and explain a proportion of the observed
      increase in severe maternal morbidity/mortality.

PMID- 29030984
TI  - Erratum.

PMID- 29030983
TI  - Woody plant encroachment amplifies spatial heterogeneity of soil phosphorus to
      considerable depth.
AB  - The geographically extensive phenomenon of woody plant encroachment into grass
      dominated ecosystems has strong potential to influence biogeochemical cycles at
      ecosystem to global scales. Previous research has focused almost exclusively on
      quantifying pool sizes and flux rates of soil carbon and nitrogen (N), while few
      studies have examined the impact of woody encroachment on soil phosphorus (P)
      cycling. Moreover, little is known regarding the impact of woody encroachment on
      the depth distribution of soil total P at the landscape scale. We quantified
      patterns of spatial heterogeneity in soil total P along a soil profile by taking
      spatially explicit soil cores to a depth of 120 cm across a subtropical savanna
      landscape that has undergone encroachment by Prosopis glandulosa (an N2 -fixer)
      and other tree/shrub species during the past century. Soil total P increased
      significantly following woody encroachment throughout the entire 120-cm soil
      profile. Large groves (>100 m2 ) and small discrete clusters (<100 m2 )
      accumulated 53 and 10 g P/m2 more soil P, respectively, compared to grasslands.
      This P accumulation in soils beneath woody patches is most likely attributable to
      P uplift by roots located deep in the soil profile (>120 cm) and transfer to
      upper portions of the profile via litterfall and root turnover. Woody
      encroachment also altered patterns of spatial heterogeneity in soil total P in
      the horizontal plane, with highest values at the centers of woody patches,
      decreasing toward the edges, and reaching lowest values in the surrounding
      grassland matrix. These spatial patterns were evident throughout the upper 1.2 m
      of the soil profile, albeit at reduced magnitude deeper in the soil profile.
      Spatial generalized least squares models indicated that fine root biomass
      explained a significant proportion of the variation in soil total P both across
      the landscape and throughout the profile. Our findings suggest that transfer of P
      from deeper soil layers enlarges the P pool in upper soil layers where it is more
      actively cycled may be a potential strategy for encroaching woody species to
      satisfy their P demands.

PMID- 29030985
TI  - AGS Notices for JAGS October 2017.

PMID- 29030986
TI  - The small molecule AU14022 promotes colorectal cancer cell death via p53-mediated
      G2/M-phase arrest and mitochondria-mediated apoptosis.
AB  - The p53 tumor suppressor plays critical roles in cell cycle regulation and
      apoptotic cell death, with its activation capable of sensitizing cancer cells to
      radiotherapy or chemotherapy. To identify small molecules that induce apoptosis
      via increased p53 transcriptional activity, we used a novel in-house library
      containing 96 small-molecule compounds. Using a cell-based screening method with
      a p53-responsive luciferase-reporter assay system involving benzoxazole
      derivatives, we found that AU14022 administration significantly increased p53
      transcriptional activity in a concentration-dependent manner. Treatment with
      AU14022 increased p53 protein expression, p53 Ser15 phosphorylation, p53-mediated
      expression of downstream target genes, and apoptosis in p53-wild-type HCT116
      human colon cancer cells, but not in p53-knockout HCT116 cells. Additionally, p53
      wild-type HCT116 cells treated with AU14022 exhibited mitochondrial dysfunction,
      including modulated expression of B-cell lymphoma-2 family proteins and
      cytochrome c release. Combination treatment with AU14022 and ionizing radiation
      (IR) synergistically induced apoptosis as compared with IR or AU14022 treatment
      alone, with further investigation demonstrating that cell cycle progression was
      significantly arrested at the G2/M phase following AU14022 treatment.
      Furthermore, in a mouse p53-wild-type HCT116 colon cancer xenograft model,
      combined treatment with AU14022 and IR inhibited tumor growth more effectively
      than radiation alone. Therefore, AU14022 treatment induced apoptosis through p53
      mediated cell cycle arrest involving mitochondrial dysfunction, leading to
      enhanced radiosensitivity in colon cancer cells. These results provide a basis
      for further assessments of AU14022 as a promising anticancer agent.

PMID- 29030987
TI  - NOD1 downregulates intestinal serotonin transporter and interacts with other
      pattern recognition receptors.
AB  - Serotonin (5-HT) is an essential gastrointestinal modulator whose effects
      regulate the intestinal physiology. 5-HT effects depend on extracellular 5-HT
      bioavailability, which is controlled by the serotonin transporter (SERT)
      expressed in both the apical and basolateral membranes of enterocytes. SERT is a
      critical target for regulating 5-HT levels and consequently, modulating the
      intestinal physiology. The deregulation of innate immune receptors has been
      extensively studied in inflammatory bowel diseases (IBD), where an exacerbated
      defense response to commensal microbiota is observed. Interestingly, many innate
      immune receptors seem to affect the serotonergic system, demonstrating a new way
      in which microbiota could modulate the intestinal physiology. Therefore, our aim
      was to analyze the effects of NOD1 activation on SERT function, as well as NOD1's
      interaction with other immune receptors such as TLR2 and TLR4. Our results showed
      that NOD1 activation inhibits SERT activity and expression in Caco-2/TC7 cells
      through the extracellular signal-regulated kinase (ERK) signaling pathway. A
      negative feedback between 5-HT and NOD1 expression was also described. The
      results showed that TLR2 and TLR4 activation seems to regulate NOD1 expression in
      Caco-2/TC7 cells. To assess the extend of cross-talk between NOD1 and TLRs, NOD1
      expression was measured in the intestinal tract (ileum and colon) of wild type
      mice and mice with individual knockouts of TLR2, and TLR4 as well as double
      knockout TLR2/TLR4 mice. Hence, we demonstrate that NOD1 acts on the serotonergic
      system decreasing SERT activity and molecular expression. Additionally, NOD1
      expression seems to be modulated by 5-HT and other immune receptors as TLR2 and
      TLR4. This study could clarify the relation between both the intestinal
      serotonergic system and innate immune system, and their implications in
      intestinal inflammation.

PMID- 29030988
TI  - MiR-145-5p inhibits proliferation and inflammatory responses of RMC through
      regulating AKT/GSK pathway by targeting CXCL16.
AB  - The main pathological characteristics of chronic glomerulonephritis (CGN) are
      diffuse mesangial cells proliferation and inflammatory responses. Our previous
      studies have confirmed that miR-145-5p was abnormally elevated in CGN rats, but
      its mechanism remains unclear. Therefore, this study aimed to elucidate the
      mechanism of miR-145-5p in regulation of renal mesangial cells proliferation and
      inflammatory responses. In vivo study, the cationic bovine serum albumin (C-BSA)
      induced CGN rat model was established, and the content of miR-145-5p in renal was
      examined by qRT-PCR, meanwhile, we also determined the renal function and
      inflammatory infiltrate. In vitro, the cell proliferation rate, cell cycle and
      inflammatory changes of rat mesangial cells (RMCs) were measured. Our results
      suggested that miR-145-5p extended the G0-G1 phase, shortened S phase, inhibited
      cell proliferation and suppressed inflammatory responses in RMCs. Moreover, miR
      145-5p inhibited CXCL16 protein expression through binding the 3'-UTR of CXCL16,
      suppressed AKT/GSK signaling pathway, and decreased expression of inflammation
      related mRNAs, such as IL-1alpha, IL-2, IL-6, and TNF-alpha mRNAs. Further,
      locking CXCL16 alleviated inflammatory reactions and down-regulated AKT/GSK
      pathway in RMCs. Above all, we concluded that miR-145-5p inhibited proliferation
      and inflammatory responses of RMCs through regulation of AKT/GSK pathway by
      targeting CXCL16.

PMID- 29030989
TI  - Genetic and epigenetic factors influencing vitamin D status.
AB  - The global prevalence of vitamin D deficiency appears to be increasing, and the
      impact of this on human health is important because of the association of vitamin
      D insufficiency with increased risk of osteoporosis, cardiovascular disease and
      some cancers. There are few studies on the genetic factors that can influence
      vitamin D levels. In particular, the data from twin and family-based studies have
      reported that circulating vitamin D concentrations are partially determined by
      genetic factors. Moreover, it has been shown that genetic variants (e.g.,
      mutation) and alteration (e.g., deletion, amplification, inversion) in genes
      involved in the metabolism, catabolism, transport, or binding of vitamin D to it
      receptor, might affect vitamin D level. However, the underlying genetic
      determinants of plasma 25-hydroxyvitamin D3 [25(OH)D] concentrations remain to be
      elucidated. Furthermore, the association between epigenetic modifications such as
      DNA methylation and vitamin D level has now been reported in several studies. The
      aim of current review was to provide an overview of the possible value of loci
      associated to vitamin D metabolism, catabolism, and transport as well epigenetic
      modification and environmental factors influencing vitamin D status.

PMID- 29030990
TI  - Novel nanohydrogel of hyaluronic acid loaded with quercetin alone and in
      combination with temozolomide as new therapeutic tool, CD44 targeted based, of
      glioblastoma multiforme.
AB  - Glioblastoma multiforme is the most common and aggressive primary brain cancer
      with only ~3% of patients surviving more than 3 years from diagnosis. Several
      mechanisms are involved in drug and radiation resistance to anticancer treatments
      and among them one of the most important factors is the tumor microenvironment
      status, characterized by cancer cell hypersecretion of interleukins and
      cytokines. The aim of our research was the synthesis of a nanocarrier of
      quercetin combined with temozolomide, to enhance the specificity and efficacy of
      this anticancer drug commonly used in glioblastoma treatment. The nanohydrogel
      increased the internalization and cytotoxicity of quercetin in human glioblastoma
      cells and, when co-delivered with temozolomide, contribute to an improved
      anticancer effect. The nanohydrogel loaded with quercetin had the ability to
      recognize CD44 receptor, a brain cancer cell marker, through an energy and
      caveolae dependent mechanism of internalization. Moreover, nanohydrogel of
      quercetin was able to reduce significantly IL-8, IL-6, and VEGF production in pro
      inflammatory conditions with interesting implications on the mechanism of
      glioblastoma cells drug resistance. In summary, novel CD44 targeted polymeric
      based nanocarriers appear to be proficient in mediating site-specific delivery of
      quercetin via CD44 receptor in glioblastoma cells. This targeted therapy lead to
      an improved therapeutic efficacy of temozolomide by modulating the brain tumor
      microenvironment.

PMID- 29030991
TI  - OMIP-041: Optimized multicolor immunofluorescence panel rat microglial staining
      protocol.

PMID- 29030992
TI  - Inadequate safety reporting in pre-eclampsia trials: a systematic evaluation.
AB  - BACKGROUND: Randomised trials and their syntheses in meta-analyses offer a unique
      opportunity to assess the frequency and severity of adverse reactions. OBJECTIVE:
      To assess safety reporting in pre-eclampsia trials. SEARCH STRATEGY: Systematic
      search using bibliographic databases, including Cochrane Central Register of
      Controlled Trials, Embase, and MEDLINE, from inception to August 2017. SELECTION
      CRITERIA: Randomised trials evaluating anticonvulsant or antihypertensive
      medication for pre-eclampsia. DATA COLLECTION AND ANALYSIS: Descriptive
      statistics appraising the adequacy of adverse reaction and toxicity reporting.
      MAIN RESULTS: We included 60 randomised trials. Six trials (10%) were registered
      with the International Clinical Trials Registry Platform, two registry records
      referred to adverse reactions, stating 'safety and toleration' and 'possible side
      effects' would be collected. Twenty-six trials (43%) stated the frequency of
      withdrawals within each study arm, and five trials (8%) adequately reported these
      withdrawals. Adverse reactions were inconsistently reported across eligible
      trials: 24 (40%) reported no serious adverse reactions and 36 (60%) reported no
      mild adverse reactions. The methods of definition or measurement of adverse
      reactions were infrequently reported within published trial reports. CONCLUSIONS:
      Pre-eclampsia trials regularly omit critical information related to safety.
      Despite the paucity of reporting, randomised trials collect an enormous amount of
      safety data. Developing and implementing a minimum data set could help to improve
      safety reporting, permitting a more balanced assessment of interventions by
      considering the trade-off between the benefits and harms. FUNDING: National
      Institute for Health Research (DRF-2014-07-051), UK; Maternity Forum, Royal
      Society of Medicine, UK. TWEETABLE ABSTRACT: Developing @coreoutcomes could help
      to improve safety reporting in #preeclampsia trials. @NIHR_DC.

PMID- 29030993
TI  - Maternal provision of non-sex-specific transformer messenger RNA in sex
      determination of the wasp Asobara tabida.
AB  - In many insect species maternal provision of sex-specifically spliced messenger
      RNA (mRNA) of sex determination genes is an essential component of the sex
      determination mechanism. In haplodiploid Hymenoptera, maternal provision in
      combination with genomic imprinting has been shown for the parasitoid Nasonia
      vitripennis, known as maternal effect genomic imprinting sex determination
      (MEGISD). Here, we characterize the sex determination cascade of Asobara tabida,
      another hymenopteran parasitoid. We show the presence of the conserved sex
      determination genes doublesex (dsx), transformer (tra) and transformer-2 (tra2)
      orthologues in As. tabida. Of these, At-dsx and At-tra are sex-specifically
      spliced, indicating a conserved function in sex determination. At-tra and At-tra2
      mRNA is maternally provided to embryos but, in contrast to most studied insects,
      As. tabida females transmit a non-sex-specific splice form of At-tra mRNA to the
      eggs. In this respect, As. tabida sex determination differs from the MEGISD
      mechanism. How the paternal genome can induce female development in the absence
      of maternal provision of sex-specifically spliced mRNA remains an open question.
      Our study reports a hitherto unknown variant of maternal effect sex determination
      and accentuates the diversity of insect sex determination mechanisms.

PMID- 29030994
TI  - Transplant tourism following the declaration of Istanbul: Poor outcomes and
      nephrologist dilemma.
AB  - AIM: Transplant tourism (TT) violates many international laws and documents.
      Despite all efforts, TT seems to be increasing. The aim of this study is to
      review outcomes of recipients of commercially transplanted kidneys since the
      Declaration of Istanbul. METHODS: All recipients of kidney transplantation done
      abroad and then returning to our centre, from September 2008 to December 2015,
      were included (tourists). Demographics and outcomes were collected from patients'
      charts. All data were compared with all recipients of living donor kidney
      transplants done at our centre (locals). RESULTS: A total of 86 tourists and 365
      locals were included. Both groups had similar age and gender. Re-grafting rates
      were the same, however, more pre-emptive transplants were done abroad. TT
      increased over time. Tourists presented early after TT, median 17.5 (IQR 7-30)
      days, and 47.7% were encountered initially in the emergency department. One-year
      graft and patient survivals were significantly lower among tourists compared with
      locals (87.2% vs. 98.0%, P < 0.001 and 90.7% vs. 98.0%, P < 0.001, respectively).
      Tourists had a significantly higher rate of acute cellular rejection (19.8% vs.
      7.1%, P < 0.001), and they sustained significantly higher rates of serious viral,
      bacterial and fungal infections compared with the locals. CONCLUSION: Transplant
      tourism seems to be increasing despite international condemnation and efforts to
      stop it. Outcomes are significantly worse when compared to local transplant
      recipients. Concerted effort is needed to better inform patients about the
      ethical and physical harms related to TT, and to point them towards ethically
      sound and medically safer alternatives.

PMID- 29030995
TI  - Magnetic resonance elastography is as accurate as liver biopsy for liver fibrosis
      staging.
AB  - BACKGROUND: Liver MR elastography (MRE) is available for the noninvasive
      assessment of liver fibrosis; however, no previous studies have compared the
      diagnostic ability of MRE with that of liver biopsy. PURPOSE: To compare the
      diagnostic accuracy of liver fibrosis staging between MRE-based methods and liver
      biopsy using the resected liver specimens as the reference standard. STUDY TYPE:
      A retrospective study at a single institution. POPULATION: In all, 200 patients
      who underwent preoperative MRE and subsequent surgical liver resection were
      included in this study. Data from 80 patients were used to estimate cutoff and
      distributions of liver stiffness values measured by MRE for each liver fibrosis
      stage (F0-F4, METAVIR system). In the remaining 120 patients, liver biopsy
      specimens were obtained from the resected liver tissues using a standard biopsy
      needle. FIELD STRENGTH/SEQUENCE: 2D liver MRE with gradient-echo based sequence
      on a 1.5 or 3T scanner was used. ASSESSMENT: Two radiologists independently
      measured the liver stiffness value on MRE and two types of MRE-based methods
      (threshold and Bayesian prediction method) were applied. Two pathologists
      evaluated all biopsy samples independently to stage liver fibrosis. Surgically
      resected whole tissue specimens were used as the reference standard. STATISTICAL
      TESTS: The accuracy for liver fibrosis staging was compared between liver biopsy
      and MRE-based methods with a modified McNemar's test. RESULTS: Accurate fibrosis
      staging was achieved in 53.3% (64/120) and 59.1% (71/120) of patients using MRE
      with threshold and Bayesian methods, respectively, and in 51.6% (62/120) with
      liver biopsy. Accuracies of MRE-based methods for diagnoses of >=F2 (90-91% [108
      9/120]), >=F3 (79-81% [95-97/120]), and F4 (82-85% [98-102/120]) were
      statistically equivalent to those of liver biopsy (>=F2, 79% [95/120], P <= 0.01;
      >=F3, 88% [105/120], P <= 0.006; and F4, 82% [99/120], P <= 0.017). DATA
      CONCLUSION: MRE can be an alternative to liver biopsy for fibrosis staging. LEVEL
      OF EVIDENCE: 3. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1268
      1275.

PMID- 29030996
TI  - Re-examining the sensitivity of HbA1c to screen for diabetes mellitus.
AB  - BACKGROUND: One of the laboratory tests recommended by the American Diabetes
      Association (ADA) to screen for diabetes mellitus (DM) is HbA1c, and it is
      particularly suitable for segments of the population that cannot or are unwilling
      to fast for a screening test. The aim of this study was to determine whether
      HbA1c would be a useful tool to screen for DM in a real-world setting if ADA
      guidelines for repeat testing to confirm the diagnosis of DM are strictly adhered
      to. METHODS: A retrospective database study was performed by extracting
      demographic and laboratory data from a chronic disease registry that collects
      data on adults from three tertiary hospitals and nine large primary care clinics
      in Singapore. Data were extracted and analyzed for adults not previously known to
      have DM whose data was captured in the registry between 2005 and 2016 with HbA1c
      and at least two diagnostic tests for DM (fasting plasma glucose or 2-h plasma
      glucose) performed within 4 weeks after HbA1c determination. RESULTS: In all,
      3928 adults were included in this study. The sensitivity, specificity, and area
      under the receiver operating characteristic curve for HbA1c at a threshold of
      6.5% were 85.2%, 82.3%, and 0.914, respectively. A higher sensitivity was found
      in female adults, younger adults, and those of non-Chinese ethnicity.
      CONCLUSIONS: The sensitivity of HbA1c as a screening test for DM in this study
      was significantly higher than that reported previously. This work provides
      additional evidence supporting the inclusion of HbA1c as one of the screening
      tests for DM.

PMID- 29030997
TI  - RNA interference and functional characterization of a tergal gland alpha amylase
      in the German cockroach, Blattella germanica L.
AB  - German cockroach males possess tergal glands that secrete a combination of
      oligosaccharides, lipids and proteins. Four major proteins occur in the
      secretion, with one being the 63 kDa alpha-amylase Blattella germanica Tergal
      Gland protein-1 (BGTG-1). Denaturing and starch gel electrophoresis coupled with
      peptide sequencing verified amylase activity for the BGTG-1 protein. BGTG-1 gene
      expression profiles were determined by using quantitative real-time PCR to
      compare messenger RNA abundance among isolated tissues of males, females and
      gravid females. Differences in BGTG-1 gene expression occurred among male
      tissues, with tergal gland tissue showing the highest expression. Tissues of
      nongravid and gravid females had significantly lower expression in comparison
      with male tergal glands (gravid females lowest). RNA interference (RNAi) was used
      to silence BGTG-1 gene expression by injecting BGTG-1 homologous double-stranded
      RNA (dsRNA) into male cockroaches. Groups injected with BGTG-1 dsRNA showed ~90%
      lower BGTG-1 gene and protein expression compared to controls, which correlated
      with lower amylase activity in colorimetric assays. However, behavioural assays
      comparing precopulatory behaviour and mating success between RNAi and control
      males did not reveal differences. These results connect amylase gene expression
      and activity in tergal gland tissue but suggest other factors, such as other
      tergal gland components, may contribute more strongly to mating success.

PMID- 29030998
TI  - Hidden biases in observational epidemiology: the case of unmeasured confounding.

PMID- 29030999
TI  - Molecular characterizations of DNA methyltransferase 3 and its roles in
      temperature tolerance in the whitefly, Bemisia tabaci Mediterranean.
AB  - The Bemisia tabaci Mediterranean (MED) cryptic species is an invasive pest,
      distributed worldwide, with high ecological adaptability and thermotolerance. DNA
      methylation (a reversible chromatin modification) is one possible change that may
      occur within an organism subjected to environmental stress. To assess the effects
      of temperature stress on DNA methyltransferase 3 (Dnmt3) in MED, we cloned and
      sequenced BtDnmt3 and identified its functions in response to high and low
      temperatures. The full-length cDNA of BtDnmt3 was 3913 bp, with an open reading
      frame of 1962 bp, encoding a 73.89 kDa protein. In situ hybridization showed that
      BtDnmt3 was expressed mainly in the posterior region. BtDnmt3 messenger RNA
      expression levels were significantly down-regulated after exposure to heat shock
      and significantly up-regulated after exposure to cold shock. Furthermore, after
      feeding on double-stranded RNA specific for BtDnmt3, both heat resistance and
      cold resistance were significantly decreased, suggesting that BtDnmt3 is
      associated with thermal stress response and indicating a differential response to
      high- and low-temperature stress in MED. Together, these results highlight a
      potential role for DNA methylation in thermal resistance, which is a process
      important to successful invasion and colonization of an alien species in various
      environments.

PMID- 29031000
TI  - Medication contaminants as a potential cause of anaphylaxis to vincristine: What
      about drug-specific antigens?

PMID- 29031001
TI  - Experimental Evaluation of (L)Au Electron-Donor Ability in Cationic Gold Carbene
      Complexes.
AB  - 29 Si NMR spectroscopy was employed to evaluate the electron donor properties of
      the (L)Au fragments in the cationic gold (beta,beta-disilyl)vinylidene complexes
      [(L)Au=C=CSi(Me)2 CH2 CH2 Si(Me)2 ]+ B(C6 F5 )4- [L=P(tBu)2 o-biphenyl or NHC]
      relative to the p-substituted aryl group in the alpha-aryl-(beta,beta
      disilyl)vinyl cations [(p-C6 H4 X)-C= CSi(Me)2 CH2 CH2 Si(Me)2 ]+ B(C6 F5 )4- .
      Similarly, 19 F NMR was employed to evaluate the sigma- and pi-electron donor
      properties of the (L)Au fragments in the neutral gold fluorophenyl complexes
      (L)Au(C6 H4 F) and in the cationic (fluorophenyl)methoxycarbene complexes
      [(L)AuC(OMe)(C6 H4 F)]+ SbF6- [L=P(tBu)2 o-biphenyl or IPr] relative to the p
      substituted aryl group of the protonated monofluorobenzophenones [(p-C6 H4 X)(C6
      H4 F)COH]+ OTf- . The results of these studies indicate that relative to p
      substituted aryl groups, the gold (L)Au fragments [L=P(tBu)2 o-biphenyl or NHC]
      are significantly more inductively electron donating and are comparable pi-donors
      and for this reason, the extent of (L)Au->C1 electron donation in gold carbene
      complexes appears to exceed that provided by a p-(dimethyamino)phenyl group.
      Furthermore, the [L=P(tBu)2 o-biphenyl]Au fragment is a nominally stronger
      electron donor than the (IPr)Au fragment, and both are significantly more
      inductively electron donating than the (PPh3 )Au and [P(OMe)3 ]Au fragments.

PMID- 29031002
TI  - Resistance training reduces metabolic syndrome and inflammatory markers in older
      women: A randomized controlled trial.
AB  - BACKGROUND: This study analyzed the effects of a 12-week resistance training (RT)
      program without dietary interventions on metabolic syndrome (MetS) components and
      inflammatory biomarkers in older women. METHODS: Fifty-three older women (mean
      [+/-SD] age 70.4 +/- 5.7 years; mean body mass index 26.7 +/- 4.0 kg/m2 ) were
      randomly assigned to a training group (TG; n = 26) that performed 12 weeks of an
      RT program or a control group (CG; n = 27) that did not perform any type of
      physical exercise over the same period. Body composition (dual energy X-ray
      absorptiometry), muscular strength (one-repetition maximum tests), blood pressure
      (BP), and blood sample measurements were performed before and after intervention.
      RESULTS: After the 12-week period, there were significantly reductions (P < 0.05)
      in glucose levels (-20.4% vs -0.3%), waist circumference (-1.5% vs +2.0%), and
      systolic BP (-6.2% vs +0.9%), and complete normalization of MetS prevalence (18%
      at baseline vs. 0% after 12-weeks RT) in the TG. Moreover, C-reactive protein and
      tumor necrosis factor-alpha concentrations decreased in the TG (-28.6% and 
      21.6%, respectively), but increased in the CG (+34.5% and +13.3%, respectively).
      In addition there were positive improvements in the MetS Z-score in the TG but
      not CG (-21.6% vs +13.3%, respectively). CONCLUSION: The results suggest that a
      12-week RT program seems to effectively reduce MetS components and inflammatory
      biomarkers in older women, regardless of dietary intervention. The RT-induced
      adaptations in body composition and inflammatory biomarkers appear to be related
      to healthy adaptations in risk factors for MetS.

PMID- 29031003
TI  - Step-by-step calculation and spreadsheet tools for predicting stressor levels
      that extirpate genera and species.
AB  - In 2011, the United States Environmental Protection Agency (USEPA) released a
      field-based method for estimating the extirpation of freshwater aquatic benthic
      invertebrates by ionic mixtures dominated by HCO3- , SO42- , and Ca2+ measured as
      specific conductivity (SC). The estimate of extirpation was SC at the 95th
      centile (XC95) of a weighted cumulative frequency distribution (CFD) of a genus
      or species over a range of SC. A CFD of XC95 values was used to predict the SC at
      which 5% of genera were likely to be extirpated. Because there are many uses for
      XC95 values and many data sets that could be analyzed using this method, we laid
      out a step-by-step method for calculating XC95 values and the stressor level that
      predicts a 5% extirpation of genera (HC05). Although the calculations can be done
      with a handheld calculator, we developed 2 downloadable Microsoft Excel(r)
      spreadsheet calculation tools that are easy to use to calculate XC95 values, to
      plot a taxon's XC95 cumulative frequency distribution with increasing SC, and to
      plot probabilities of observing a taxon at a particular SC. They also plot
      cumulative frequency distributions of XC95 values and calculate HC05 values. In
      addition to the tools, we share an example and the output of XC95 values for 176
      distinct aquatic benthic invertebrates in Appalachia, in West Virginia, USA.
      Integr Environ Assess Manag 2018;14:174-180. (c) 2017 SETAC.

PMID- 29031004
TI  - Starting a uterus transplantation service: notes from a small island.

PMID- 29031005
TI  - Quantitative high-content/high-throughput microscopy analysis of lipid droplets
      in subject-specific adipogenesis models.
AB  - Neutral lipids packed in lipid droplets (LDs) are essential as a source of fuel
      for organisms, and specialized storing cells, the adipocytes, provide a buffer
      for energy variations. Many modern-society-disorders are connected with excess
      accumulation or deficiency of LDs in adipose tissue. Intracellular LD number and
      size distribution reflect the tissue conditions, while the associated mechanisms
      and genes rs are still poorly understood. Large-scale genetic screens using human
      in vitro differentiated primary adipocytes require cell samples donated from many
      patients. The heterogeneity appearing between donors highlighted the need for
      high-throughput methods robust to individual variations. Previous image analysis
      algorithms failed to handle individual LDs, but focused on averages, hiding
      population heterogeneity. We present a new high-content analysis (HCA) technique
      for analysis of fat cell metabolism using data from a large-scale RNAi screen
      including images of more than 500 k in vitro differentiated adipocytes from three
      donors. The RNAi-based suppression of Perilipin 1 (PLIN1), a protein involved in
      the adipocyte lipid metabolism, served as a positive control, while cells treated
      with randomized RNA served as negative controls. We validate our segmentation by
      comparing our results to those of previously published methods: We also evaluate
      the discriminative power of different morphological features describing LD size
      distribution. Classification of cells as containing few large or many small LDs
      followed by calculating the percentage of cells in each class proved to
      discriminate the positive PLIN1-suppressed phenotype from the untreated negative
      control with an area under the receiver operating characteristic curve of 0.98.
      The results suggest that this HCA method offers improved segmentation and
      classification accuracy, and can, thus, be utilized to quantify changes in LD
      metabolism in response to treatment in many cell models relevant to a variety of
      diseases. (c) 2017 International Society for Advancement of Cytometry.

PMID- 29031006
TI  - The kidney and cardiovascular outcome trials.
AB  - Chronic kidney disease (CKD) affects a substantial minority of people with type 2
      diabetes (T2D). Analysis of US National Health and Nutrition Examination Survey
      (NHANES) datasets from 2007 through 2012 showed Stage 3 or worse disease
      (estimated glomerular filtration rate [eGFR] <60 mL/min per 1.73 m2 ) in nearly
      one in five patients, with increasing age, blood pressure, obesity, and levels of
      glycemia all associated with higher likelihood of Stage 3 or worse CKD,
      comparable to findings from surveys from many other areas, which also show micro-
      or macroalbuminuria to be present in one-sixth to one-third of diabetic people.
      Improvement in albuminuria has been shown in clinical trials of glycemic
      interventions, including the Action to Control Cardiovascular Disease in Diabetes
      (ACCORD) trial, the Action in Diabetes and Vascular Disease: Preterax and
      Diamicron MR Controlled Evaluation (ADVANCE) trial, in which the nephroprotective
      effect of blood pressure lowering was also demonstrated, and the UK Prospective
      Diabetes Study (UKPDS). However, over the past decade a host of cardiovascular
      outcome trials (CVOTs) have been performed with newer T2D therapeutic agents, and
      many of these have included intriguing information pertaining to renal disease
      and renal outcomes not necessarily related to changes in glycemia. It is of
      interest to review some of these findings. Glucagon-like peptide-1 (GLP-1) has
      been reported to increase glomerular filtration rate (GFR), renal blood flow, and
      the fractional excretion both of sodium and potassium, with renal GLP-1 receptors
      present in afferent arteriolar vascular smooth muscle cells, glomerular
      endothelial cells and macrophages, juxtaglomerular cells, and the proximal
      tubule, perhaps mediating the greater natriuresis seen after oral than
      intravenous sodium. In the Liraglutide Effect and Action in Diabetes: Evaluation
      of Cardiovascular Outcome Results (LEADER) trial, the significant 13% reduction
      in the primary composite outcome of cardiovascular death, myocardial infarction,
      and stroke was found on subgroup analysis to particularly occur among
      participants with Stage 3 CKD, having eGFR 30-59 mL/min per 1.73 m2 . No
      significant effect on eGFR was found with liraglutide, although both those
      receiving and not receiving the drug showed a decline in eGFR from approximately
      75 to 65 mL/min per 1.73 m2 over the 48-month period of observation. Liraglutide
      administration was associated with a significant reduction in albuminuria, with
      nearly a 25% lower likelihood of development of macroalbuminuria, and with the
      albumin:  creatinine ratio (ACR) approximately 20% lower among treated people,
      regardless of the baseline level of eGFR. Similarly, in the Evaluation of
      Lixisenatide in Acute Coronary Syndrome (ELIXA) trial, a 34% increase in the
      urine ACR was reported among people receiving placebo, but the increase was 24%
      among those receiving lixisenatide, and in the Trial to Evaluate Cardiovascular
      and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes
      (SUSTAIN-6), persistent macroalbuminuria developed among 2.7% of those receiving
      semaglutide, but among 4.9% of those receiving placebo. The enzyme dipeptidyl
      peptidase (DPP)-4 is, like the GLP-1 receptor, present in multiple renal membrane
      bound locations, including afferent arteriolar vascular smooth muscle cells,
      mesangial cells, podocytes, and proximal tubular cells, and DPP-4 inhibitors
      appear to have salutary effects on albuminuria similar to those of the GLP-1
      agents. In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients
      with Diabetes Mellitus (SAVOR)-Thrombolysis in Myocardial Infarction (TIMI) 53
      trial, saxagliptin was associated with significantly less worsening and more
      improvement in microalbumin levels at 1 year, at 2 years, and by end-of
      treatment. The reduction in microalbumin levels was similar in patients with and
      without renal impairment. Interestingly, there was no relationship between
      improvement in albuminuria and improvement in HbA1c. The other DPP4i CVOTs have
      not reported effects of these agents on renal function or albuminuria, but
      studies of sitagliptin and linagliptin suggest that these agents may also reduce
      albuminuria. Sodium-glucose cotransporter (SGLT) 2 inhibitors affect multiple
      sites, with the potential to affect renal function. The Canagliflozin
      Cardiovascular Assessment Study (CANVAS) showed a 27% reduction in progression of
      albuminuria, with a 40% reduction in eGFR, need for renal-replacement therapy, or
      death from renal causes associated with the use of canagliflozin. After a fall in
      mean eGFR with canagliflozin from 76 to 73 mL/min per 1.73 m2 at 3 months, eGFR
      remained stable through 6 years while gradually declining during the period of
      observation with placebo. Evidence of dual effects of SGLT2 inhibition on both
      albuminuria and GFR was even more strongly shown in the Empagliflozin
      Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG
      OUTCOME); in that CVOT, although there was an initial decline in eGFR with
      empagliflozin, from 94 mL/min per 1.73 m2 through 192 weeks, eGFR was
      consistently higher with empagliflozin, although this was less clear in trial
      participants with baseline eGFR <60 mL/min per 1.73 m2 . Empagliflozin also
      reduced the development of acute renal failure. Further analysis showed
      empagliflozin to be associated with a reduction in albuminuria, regardless of the
      baseline urine albumin level. The CVOTs have offered the possibility that
      diabetes treatment may move beyond surrogate endpoints to actual cardiovascular
      outcome benefits. It appears that these drugs will also lead to a reduction in
      adverse renal outcomes. We should look with optimism at this potential approach
      to a major complication of diabetes.

PMID- 29031007
TI  - Acenequinocumulenes: Lateral and Vertical pi-Extended Analogues of
      Tetracyanoquinodimethane (TCNQ).
AB  - We have designed a series of molecules and developed synthetic methodology that
      allows for the inclusion of structural diversity along both the lateral and
      vertical axes of the basic TCNQ skeleton. In the lateral direction,
      benzoannulation extends the pi-system through (hetero)acene formation, whereas
      incorporation of a [3]cumulene increases delocalization vertically. The potential
      of these new molecules as semiconductors is explored through UV/Vis spectroscopy,
      cyclic voltammetry, X-ray crystallography, thin-film formation, and mobility
      measurements (using space charge limited current measurements).

PMID- 29031008
TI  - Identification of a novel homozygous TRAPPC9 gene mutation causing non-syndromic
      intellectual disability, speech disorder, and secondary microcephaly.
AB  - TRAPPC9 gene mutations have been linked recently to autosomal recessive mental
      retardation 13 (MRT13; MIM#613192) with only eight families reported world-wide.
      We assessed patients from two consanguineous pedigrees of Pakistani descent with
      non-syndromic intellectual disability and postnatal microcephaly through whole
      exome sequencing (WES) and cosegregation analysis. Here we report six further
      patients from two pedigrees with homozygous TRAPPC9 gene mutations, the novel
      nonsense mutation c.2065G>T (p.E689*) and the previously identified nonsense
      mutation c.1423C>T (p.R475*). We provide an overview of previously reported
      clinical features and highlight common symptoms and variability of MRT13. Common
      findings are intellectual disability and absent speech, and frequently
      microcephaly, motor delay and pathological findings on MRI including diminished
      cerebral white matter volume are present. Mutations in TRAPPC9 should be
      considered in non-syndromic autosomal recessive intellectual disability with
      severe speech disorder.

PMID- 29031009
TI  - Fabrication of biodegradable foams for deep tissue negative pressure treatments.
AB  - Devices for negative pressure wound therapy (NPWT) rely on compressible foams
      operating at the tissue-device interface. Clinically used foams are nonabsorbable
      and if used on deep wounds or left in place for an extended period of time,
      excessive cell ingrowth and formation of granulation tissue into the foam may
      require a surgical procedure to remove the foam. Foams with fast degradation and
      with low immunogenicity and fibrotic response are required. Foams composed of
      combinations of poly(lactide-co-glycolide) (PLGA), poly(lactide-co-caprolactone)
      (PLCL), and polycaprolactone (PCL) were created by combined salt leaching and
      solvent displacement protocols. In vitro and in vivo degradation studies and
      mechanical properties of foams were evaluated and compared to clinically used
      poly(vinyl alcohol) (PVA) foam and PCL foams. Foams composed of PLGA (50:50
      lactide:glycolide) of low molecular weight blended with PCL maintained mechanical
      properties and degraded significantly after 21 days of subcutaneous implantation
      in rats. The most ideal formulations for use in NPWT were identified as
      copolymeric PLGA (Mn 3000 Da) at a lactide:glycolide ratio of 50:50 combined with
      PCL at either a 75:25 or 50:50 ratio, and copolymeric PLGA (Mn 7500 Da) at a
      lactide:glycolide ratio of 50:50 combined with PCL at a 50:50 ratio. (c) 2017
      Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1998
      2007, 2018.

PMID- 29031010
TI  - Evaluation of aprepitant for acute chemotherapy-induced nausea and vomiting in
      children and adolescents with acute lymphoblastic leukemia receiving high-dose
      methotrexate.
AB  - BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) negatively impacts
      patients' quality of life. The emetogenicity of high-dose methotrexate in
      children and adolescents with cancer is incompletely characterized. At our
      institution, a number of patients with acute lymphoblastic leukemia (ALL) have
      received aprepitant with courses of high-dose methotrexate after poor CINV
      control with prior courses. PROCEDURE: We conducted a retrospective cohort
      analysis on patients with ALL who received methotrexate 5 g/m2 /dose with and
      without concomitant aprepitant at Texas. Children's Hospital between October 1,
      2010 and January 31, 2016. RESULTS: We identified 16 patients who received a
      total of 69 courses of methotrexate. An enhanced antiemetic regimen containing
      aprepitant was administered with 42 methotrexate courses and resulted in a 54%
      reduction in the use of as-needed antiemetics (P = 0.002, 95% CI: 21-89%). There
      were no statistically significant differences in methotrexate area under the
      curve values (2,209 MUM?hr/l +/- 151 vs. 2,051 MUM?hr/l +/- 94, P = 0.355) or end
      infusion methotrexate concentrations (80.5 MUM +/- 5.6 vs. 74.7 MUM +/- 3.2, P =
      0.335) in patients receiving a standard versus an enhanced antiemetic regimen.
      CONCLUSIONS: The addition of aprepitant reduces both CINV and the use of rescue
      antiemetics. Aprepitant does not appear to affect the pharmacokinetics of
      methotrexate. Granisetron was prescribed more frequently than ondansetron, but
      selection of secondary and tertiary agents, if any, was highly variable.

PMID- 29031011
TI  - A framework for the identification of hotspots of climate change risk for
      mammals.
AB  - As rates of global warming increase rapidly, identifying species at risk of
      decline due to climate impacts and the factors affecting this risk have become
      key challenges in ecology and conservation biology. Here, we present a framework
      for assessing three components of climate-related risk for species:
      vulnerability, exposure and hazard. We used the relationship between the observed
      response of species to climate change and a set of intrinsic traits (e.g. weaning
      age) and extrinsic factors (e.g. precipitation seasonality within a species
      geographic range) to predict, respectively, the vulnerability and exposure of all
      data-sufficient terrestrial non-volant mammals (3,953 species). Combining this
      information with hazard (the magnitude of projected climate change within a
      species geographic range), we identified global hotspots of species at risk from
      climate change that includes the western Amazon basin, south-western Kenya, north
      eastern Tanzania, north-eastern South Africa, Yunnan province in China, and
      mountain chains in Papua-New Guinea. Our framework identifies priority areas for
      monitoring climate change effects on species and directing climate mitigation
      actions for biodiversity.

PMID- 29031012
TI  - The role of diabetes mellitus and BMI in the surgical treatment of ankle
      fractures.
AB  - BACKGROUND: Open reduction and internal fixation is the standard treatment for
      displaced ankle fractures. However, the presence of comorbidities such as
      diabetes mellitus and body mass index (BMI) are associated with poor bone
      quality, and these factors may predict the development of postoperative
      complications. The study aim was to assess the role of diabetes mellitus and BMI
      in wound healing in patients younger than 65 years who were surgically treated
      for malleoli fractures. METHODS: Ninety patients, aged from 18 to 65 years old,
      with surgically treated ankle fracture, were retrospectively enrolled. Patients
      were classified in two groups: patient with diabetes and patients without
      diabetes (insulin-dependent and noninsulin dependent). All patients were assessed
      for wound complications, Visual Analogue Scale and Foot and Ankle Disability
      Index (FADI) were assessed for all patients. Logistic regression was used to
      identify the risk of wound complications after surgery using the following
      factors as explanatory variables: age, gender, duration of surgery, BMI,
      hypercholesterolemia, smoking history, diabetes mellitus, and high blood
      pressure. RESULTS: In total, 38.9% of patients showed wound complications. Of
      them, 17.1% were nondiabetics and 82.9% were diabetics. We observed a significant
      association between DM and wound complications after surgery (P = .005). Logistic
      regression analysis revealed that DM (P < .001) and BMI (P = .03) were associated
      with wound complications. The odds of having a postoperative wound complication
      were increased 0.16 times in the presence of diabetes and 1.14 times for
      increasing BMI. CONCLUSION: This study showed that diabetes mellitus and higher
      BMI delay the wound healing and increase the complication rate in young adult
      patients with surgically treated bimalleolar fractures.

PMID- 29031013
TI  - Intragenic hypomethylation of DNMT3A in patients with myelodysplastic syndrome.
AB  - BACKGROUND: DNMT3A is a DNA methyltransferase that acts in de novo methylation.
      Aberrant expression of DNMT3A has been reported in several human diseases,
      including myelodysplastic syndrome (MDS). However, the pattern of DNMT3A
      methylation remains unknown in MDS. METHODS: The present study was aimed to
      investigate the methylation status of DNMT3A intragenic differentially methylated
      region 2 (DMR2) using real-time quantitative methylation-specific PCR and analyze
      its clinical significance in MDS. RESULTS: Aberrant hypomethylation of DNMT3A was
      found in 57% (51/90) MDS cases. There were no significant differences in age,
      sex, white blood cell counts, platelet counts, hemoglobin counts and World Health
      Organization, International Prognostic Scoring System and karyotype
      classifications between DNMT3A hypomethylated and DNMT3A hypermethylated groups.
      However, the patients with DNMT3A hypomethylation had shorter overall survival
      time than those without DNMT3A hypomethylation (11 months vs. 36 months,
      p=0.033). Multivariate analysis confirmed the independent adverse impact of
      DNMT3A hypomethylation in MDS. CONCLUSIONS: Our data suggest that DNMT3A DMR2
      hypomethylation may be a negative prognostic hallmark in MDS.

PMID- 29031014
TI  - Indirect method for validating transference of reference intervals.
AB  - BACKGROUND: Transference of reference intervals (RIs) from multicentre studies
      are often verified by use of a small number of samples from reference individuals
      or by the use of one serum sample (Serum X for NORIP RI). Despite recommended and
      appropriate methods, both have inconveniencies and drawbacks. Several attempts
      have been made to develop an indirect method, which uses historical data from the
      laboratory. These methods are retrospective relying on older test results. A near
      prospective method would be preferable for the laboratories introducing new
      methods or changing analytical platforms. METHODS: We performed a data mining
      experiment using results from our laboratory information system covering patients
      from a large geographic area. Request patterns for patients with assumed healthy
      characteristics were identified and used to extract laboratory results for
      calculation of new RI by an indirect method. Calculated RI and confidence
      intervals (CIs) were compared to transferred NORIP RI verified by NFKK Reference
      Serum X. RESULTS: We found that our indirect method and NFKK Reference Serum X in
      general produced similar results when verifying transference of RI. The method
      produces results for all stratifications. Only single stratifications and one
      analyte showed unexplained incongruences to the NORIP RI. CONCLUSIONS: Our
      results suggest using request patterns as a surrogate measure for good health
      status. This allows for a data mining method for validation of RI or validating
      their transference, which is likely to be applicable in countries with similar
      healthcare and laboratory information system.

PMID- 29031016
TI  - Preanalytics of ammonia: stability, transport and temperature of centrifugation.

PMID- 29031015
TI  - The venous thromboembolic risk and the clot wave analysis: a useful relationship?
AB  - BACKGROUND: Hospitalized patients with acute medical conditions have higher
      venous thromboembolism (VTE) risk. A patient with a final Padua Prediction Score
      (PPS) of >=4 is considered to be at high risk for VTE. The aim of this study was
      to investigate on a possible relationship between PPS, the dynamics of the clot
      formation, i.e. the clot waveform analysis (CWA) of aPTT, fibrinogen and D-Dimer
      in a large group of medical patients. METHODS: CWA in terms of velocity (first
      derivative), acceleration (second derivative), density (Delta) of aPTT,
      fibrinogen, D-Dimer and PPS for VTE were determined in 801 medical patients
      divided in three groups (without antithrombotic prophylaxis and high PPS, without
      antithrombotic prophylaxis and low PPS, with antithrombotic prophylaxis and high
      PPS) and a group of healthy subjects. RESULTS: CWA, fibrinogen and D-Dimer values
      were higher in the medical patients with high PPS with or without antithrombotic
      prophylaxis when compared with patients without antithrombotic prophylaxis with
      low PPS and healthy subjects. The second derivative, fibrinogen and D-Dimer were
      significantly associated with a high PPS score (>=4): odds ratio (OR) = 1.53, 95%
      confidence interval (CI) = 1.03-2.28; OR = 1.91, 95% CI = 1.3-2.79; OR = 3.16,
      95% CI = 2.29-4.36, respectively. Interactions between first derivative and D
      Dimer (OR = 2.14, 95% CI = 1.23-3.72) and first derivative and fibrinogen (OR =
      1.75, 95% CI = 1.02-2.98) were found. CONCLUSIONS: CWA could give useful
      information to recognize a hypercoagulable state in patients admitted to a
      medical ward with high and low PPS. First and second derivative aPTT, D-Dimer and
      fibrinogen levels could be added to PPS to better assess the global
      thromboembolic risk of these patients.

PMID- 29031017
TI  - How to reduce scientific irreproducibility: the 5-year reflection.
AB  - We discuss in depth six causes of scientific irreproducibility and their
      ramifications for the clinical sciences: fraud, unfounded papers published by
      prominent authorities, bias, technical deficiencies, fragmented science and
      problems with big data. Some proposed methods to combat this problem are briefly
      described, including an effort to replicate results from some high impact papers
      and a proposal that authors include detailed preclinical data in papers with
      supposedly high translational value. We here advocate for a 5-year reflection on
      papers with seemingly high clinical/translational potential, published alongside
      the original paper where authors reflect on the quality, reproducibility and
      impact of their findings. These reflections can be used as a benchmark for
      credibility, and begin a virtuous cycle of improving the quality of published
      findings in the literature.

PMID- 29031018
TI  - Strategies to define performance specifications in laboratory medicine: 3 years
      on from the Milan Strategic Conference.
AB  - Measurements in clinical laboratories produce results needed in the diagnosis and
      monitoring of patients. These results are always characterized by some
      uncertainty. What quality is needed and what measurement errors can be tolerated
      without jeopardizing patient safety should therefore be defined and specified for
      each analyte having clinical use. When these specifications are defined, the
      total examination process will be "fit for purpose" and the laboratory
      professionals should then set up rules to control the measuring systems to ensure
      they perform within specifications. The laboratory community has used different
      models to set performance specifications (PS). Recently, it was felt that there
      was a need to revisit different models and, at the same time, to emphasize the
      presuppositions for using the different models. Therefore, in 2014 the European
      Federation of Clinical Chemistry and Laboratory Medicine (EFLM) organized a
      Strategic Conference in Milan. It was felt that there was a need for more
      detailed discussions on, for instance, PS for EQAS, which measurands should use
      which models to set PS and how to set PS for the extra-analytical phases. There
      was also a need to critically evaluate the quality of data on biological
      variation studies and further discussing the use of the total error (TE) concept.
      Consequently, EFLM established five Task Finish Groups (TFGs) to address each of
      these topics. The TFGs are finishing their activity on 2017 and the content of
      this paper includes deliverables from these groups.

PMID- 29031019
TI  - Reply to: Analytical evaluation of the performances of Diazyme and BRAHMS
      procalcitonin applied to Roche Cobas in comparison with BRAHMS PCT-sensitive
      Kryptor.

PMID- 29031020
TI  - Fetal MRI, lower acceptance by women in research vs. clinical setting.
AB  - AIM: To determine acceptance of pregnant women to undergo fetal magnetic
      resonance imaging (MRI) examination in research and clinical setting. METHODS: A
      prospective study included a research group [part of a study comparing brain
      ultrasound (US) to MRI in fetuses at risk for acquired brain damage] and a
      clinical group [fetuses with suspected (brain) anomalies after structural US
      examination] from 2011 to 2014. All women were advised to use sedatives. MRI
      declinations, use of sedation, MRI duration and imaging quality were compared
      between both groups. RESULTS: Study participation was accepted in 57/104 (55%)
      research cases. Fetal MRI was performed in 34/104 (33%) research and 43/44 (98%)
      clinical cases. Reasons to decline study participation were MRI related in 41%,
      and participation was too burdensome in 46%. Acceptance was highest for
      indication infection and lowest in alloimmune thrombocytopenia and monochorionic
      twin pregnancy. Sedatives were used in 14/34 research and 43/43 clinical cases.
      Scan duration and quality were comparable (21 and 20 min in research and clinical
      cases, respectively, moderate/good quality in both groups). CONCLUSIONS: Pregnant
      women consider MRI more burdensome than professionals realize. Two-third of women
      at risk for fetal brain damage decline MRI examination. Future studies should
      evaluate which information about fetal MRI is supportive.

PMID- 29031021
TI  - Re: Utility of routine urine CMV PCR and total serum IgM testing of small for
      gestational age infants: a single center review.

PMID- 29031022
TI  - Fetal analysis with invasive method (FA-I) and fetal analysis with non-invasive
      method (FA-NI): replacing current, deceptively imprecise clinical nomenclature.
AB  - There is a problem with the current nomenclature of prenatal evaluation. The
      current nomenclature of "prenatal testing" and "prenatal screening" - along with
      their subsets of "ultrasound testing," "ultrasound screening," "non-invasive
      prenatal testing," "non-invasive prenatal screening," and "prenatal diagnosis" -
      has become so imprecise that clinical misinterpretation and distortion of the
      informed consent process are increasingly difficult to avoid. To remedy this
      problem, we propose a new, precise nomenclature: "fetal analysis with invasive
      method" (FA-I) and "fetal analysis with non-invasive method," (FANI) using
      various techniques. This new nomenclature is designed to be precise and therefore
      facilitate effective communication among physicians and with pregnant women. For
      ease of use the new nomenclature can be formulated as an abbreviation: FA-I and
      FA-NI.

PMID- 29031023
TI  - Whole-Body Vibration Combined with Treadmill Training Improves Walking
      Performance in Post-Stroke Patients: A Randomized Controlled Trial.
AB  - BACKGROUND Stroke is characterized by an asymmetrical gait pattern that causes
      poor stability and reduces overall activity levels. The aim of this study was to
      investigate the effect of whole-body vibration combined with treadmill training
      (WBV-TT) on walking performance in patients with chronic stroke. MATERIAL AND
      METHODS Thirty ambulatory chronic stroke patients were randomly allocated to the
      WBV-TT group or the treadmill training (TT) group. The participants in the WBV-TT
      group performed 6 types of exercises on a vibrating platform for 4.5 minutes and
      then walked on the treadmill for 20 minutes. The participants in the TT group
      conducted the same exercise on a platform without vibration and then walked on
      the treadmill in the same manner. The vibration lasted for 45 seconds in each
      exercise, and the intervention was performed 3 times weekly for 6 weeks. The
      treadmill walking speed was gradually increased by 5% in both groups. The outcome
      measures included the temporospatial parameter of gait (GAITRite(r)) and 6-minute
      walk test. RESULTS The WBV-TT group showed significant improvements in walking
      performance with respect to walking speed, cadence, step length, stride length,
      single-limb support, double-limb support, and 6-minute walk test compared with
      baseline (p<0.05). Significant improvements were also seen in walking speed, step
      length, stride length, and double-limb support compared with the TT group
      (p<0.05). CONCLUSIONS These findings indicate that WBV-TT is more effective than
      TT for improving walking performance of patients with chronic stroke.

PMID- 29031024
TI  - Use of a LYSO-based Compton camera for prompt gamma range verification in proton
      therapy.
AB  - PURPOSE: A Compton camera (CC), which measures prompt gammas (PGs) emitted during
      proton therapy, is a potentially useful imaging device for proton range
      verification. The aim of this study was to evaluate how well the reconstructed PG
      images obtained from various two-stage CC configurations reproduce the distal
      falloff of the PG emission. METHODS: We conducted Monte Carlo simulations to
      evaluate different two-stage CCs positioned orthogonal to a proton pencil beam
      irradiating a water phantom. The results were compared with those obtained for a
      three-stage CC. In particular, all detectors were made of lutetium-yttrium
      orthosilicate (LYSO) crystals. RESULTS: We found that: (a) the position
      resolution of the detector led to more uncertainty in predicting the depth of
      maximum emission and distal falloff positions than did the energy resolution of
      the detector; (b) reducing the thickness of the absorber detector reduces the
      effect of position resolution on the quality of reconstructed images and improves
      falloff position estimates; (c) incomplete absorption of PGs can be filtered by
      restricting incident gamma energies to known PG energy spectral peaks; and (d)
      there is greater bias and less accuracy in predicting distal falloff positions
      with the three-stage CC compared with the two-stage CC. CONCLUSIONS: This study
      demonstrates the feasibility of using various CC designs and event selection
      methods to improve the imaging of PG rays. In our designed two-stage CCs, the
      thin LYSO-based absorber can provide better predictions of the distal falloff
      positions than the thick one. Compared to three-stage CCs, two-stage CCs are less
      biased and provide more accurate range verification.

PMID- 29031025
TI  - Measurement Variation and Repeatability of Echocardiographic Variables Used to
      Estimate Pulmonary Artery Pressure in Dogs.
AB  - BACKGROUND: Pulmonary hypertension (PH) is an important clinical entity in dogs.
      Pulmonary hypertension is generally identified based on echocardiographic
      findings, but measurement variation of the variables most often used in this
      context has not been reported. OBJECTIVE: To define measurement variation of
      echocardiographic variables that are used to estimate pulmonary artery pressure.
      ANIMALS: Four dogs with subclinical tricuspid valve regurgitation were selected
      from a hospital population. METHODS: Prospective descriptive study - dogs were
      subject to repeated echocardiographic examination by 2 operators. Each dog was
      echocardiographically examined 12 times, once by each operator during mornings
      and afternoons of 3 nonconsecutive days. Measurement variation was defined by
      coefficients of variation and by mean square errors (MSE) from ANOVA models.
      Repeatability coefficients (RC) were calculated from MSE. RESULTS: Of 50 within
      day, between-day, and interoperator coefficients of variation (CVs), 37 were less
      than 10% and 46 were less than 15%. The range of peak velocity of tricuspid valve
      regurgitation (VTR) VTR was 1.87-3.34 m/s. Analysis of variance revealed a
      significant effect (P < 0.05) of operator for 7 of 10 measurements. Within
      operator/between-day/within-subject and between-operator/between-day/within
      subject RCs of VTR were, respectively, 0.3 and 0.6 m/s. CONCLUSIONS AND CLINICAL
      IMPORTANCE: With regard to repeatability, VTR is superior to other methods used
      for echocardiographic estimation of systolic pulmonary artery pressure. When TR
      is absent, the acceleration time of pulmonary ejection and the acceleration-to
      ejection time ratio are alternative measures. A change in VTR exceeding 0.3 m/s
      might be outside the range of expected within-operator variation.

PMID- 29031026
TI  - Genome-wide characterization of differential transcript usage in Arabidopsis
      thaliana.
AB  - Alternative splicing and the usage of alternate transcription start- or stop
      sites allows a single gene to produce multiple transcript isoforms. Most plant
      genes express certain isoforms at a significantly higher level than others, but
      under specific conditions this expression dominance can change, resulting in a
      different set of dominant isoforms. These events of differential transcript usage
      (DTU) have been observed for thousands of Arabidopsis thaliana, Zea mays and
      Vitis vinifera genes, and have been linked to development and stress response.
      However, neither the characteristics of these genes, nor the implications of DTU
      on their protein coding sequences or functions, are currently well understood.
      Here we present a dataset of isoform dominance and DTU for all genes in the
      AtRTD2 reference transcriptome based on a protocol that was benchmarked on
      simulated data and validated through comparison with a published reverse
      transciptase-polymerase chain reaction panel. We report DTU events for 8148 genes
      across 206 public RNA-Seq samples, and find that protein sequences are affected
      in 22% of the cases. The observed DTU events show high consistency across
      replicates, and reveal reproducible patterns in response to treatment and
      development. We also demonstrate that genes with different evolutionary ages,
      expression breadths and functions show large differences in the frequency at
      which they undergo DTU, and in the effect that these events have on their protein
      sequences. Finally, we showcase how the generated dataset can be used to explore
      DTU events for genes of interest or to find genes with specific DTU in samples of
      interest.

PMID- 29031027
TI  - Evaluation of Renal Perfusion in Hyperthyroid Cats before and after Radioiodine
      Treatment.
AB  - BACKGROUND: Hyperthyroidism and chronic kidney disease (CKD) are common in
      elderly cats. Consequently, both diseases often occur concurrently. Furthermore,
      renal function is affected by thyroid status. Because changes in renal perfusion
      play an important role in functional renal changes in hyperthyroid cats,
      investigation of renal perfusion may provide novel insights. OBJECTIVES: To
      evaluate renal perfusion in hyperthyroid cats with contrast-enhanced ultrasound
      (CEUS). ANIMALS: A total of 42 hyperthyroid cats was included and evaluated
      before and 1 month after radioiodine treatment. METHODS: Prospective intrasubject
      clinical trial of contrast-enhanced ultrasound using a commercial contrast agent
      (SonoVue) to evaluate renal perfusion. Time-intensity curves were created, and
      perfusion parameters were calculated by off-line software. A linear mixed model
      was used to examine differences between pre- and post-treatment perfusion
      parameters. RESULTS: An increase in several time-related perfusion parameters was
      observed after radioiodine treatment, indicating a decreased blood velocity upon
      resolution of the hyperthyroid state. Furthermore, a small post-treatment
      decrease in peak enhancement was present in the renal medulla, suggesting a lower
      medullary blood volume. CONCLUSIONS AND CLINICAL IMPORTANCE: Contrast-enhanced
      ultrasound indicated a higher cortical and medullary blood velocity and higher
      medullary blood volume in hyperthyroid cats before radioactive treatment in
      comparison with 1-month post-treatment control.

PMID- 29031028
TI  - Risk Factors for Death in Dogs Treated for Esophageal Foreign Body Obstruction: A
      Retrospective Cohort Study of 222 Cases (1998-2017).
AB  - BACKGROUND: Limited data exist describing risk factors for death, and long-term
      outcomes in dogs with esophageal foreign body (EFB) obstruction.
      HYPOTHESIS/OBJECTIVES: To evaluate short- and long-term outcomes, and analyze
      risk factors for death in dogs with EFB obstruction. We hypothesized duration of
      entrapment and treatment type would affect outcome. ANIMALS: A total of 222 dogs
      were treated for EFB obstruction at an emergency and referral hospital between
      March 1998 and March 2017. METHODS: Medical records for dogs with EFB were
      retrospectively evaluated. RESULTS: Foreign material most frequently was osseous
      (180/222 [81%]), with distal esophagus the most common location (110/222
      [49.5%]). Duration of clinical signs was not associated with risk of death (OR =
      1.08, 95% CI 0.99-1.17; P = 0.2). Entrapment was treated by endoscopy (204/222
      [91.8%]), surgery after endoscopic attempt (13/222 [5.9%]), and repeat endoscopy
      after surgery was recommended but declined (5/222 [2.3%]). In-hospital case
      fatality rate was 11/222 (5%). Risk of death was significantly higher with
      surgery (OR = 20.1, 95% CI 3.59-112.44; P = 0.001), and 5/5 (100%) of dogs died
      if undergoing endoscopy after surgery was recommended but declined. Increasing
      numbers of postprocedural complications (OR = 3.44, CI 2.01-5.91; P < 0.001),
      esophageal perforation (OR = 65.47, CI 4.27-1004.15; P = 0.003), and
      postprocedure esophageal hemorrhage (OR = 11.81, CI 1.19-116.77; P = 0.04)
      increased in-hospital risk of death. Esophageal strictures were reported in 4/189
      (2.1%) of survivors available for follow-up. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Death is uncommon in canine EFB; however, treatment type affects outcome, and
      these data should be used to guide decision-making in dogs with EFB.

PMID- 29031029
TI  - Glutathione Peroxidase Activity, Plasma Total Antioxidant Capacity, and Urinary
      F2- Isoprostanes as Markers of Oxidative Stress in Anemic Dogs.
AB  - BACKGROUND: Oxidative stress plays a role in the pathophysiology of several
      diseases and has been documented as a contributor to disease in both the human
      and veterinary literature. One at-risk cell is the erythrocyte, however, the role
      of oxidative stress in anemia in dogs has not been widely investigated.
      HYPOTHESIS/OBJECTIVE: Anemic dogs will have an alteration in the activity of
      glutathione peroxidase (GPx), a decrease in of total antioxidant capacity (TAC),
      and an increased concentration of urinary 15-F2 -isoprostanes (F2 -IsoP) when
      compared to healthy dogs. ANIMALS: 40 client-owned dogs with anemia (PCV <30%)
      age-matched to 40 client-owned healthy control dogs. METHODS: Prospective, cross
      sectional study. Whole blood GPx activity, plasma TAC, and urinary F2 
      isoprostane concentrations were evaluated in each dog and compared between
      groups. RESULTS: Anemic dogs had significantly lower GPx activity (43.1 * 103 +/-
      1.6 * 103 U/L) than did dogs in the control group (75.8 * 103 +/- 2.0 * 103 U/L;
      P < 0.0001). The GPx activity in dogs with hemolysis (103 +/- 0.8 * 103 U/L) was
      not significantly different (P = 0.57) than in dogs with nonhemolytic anemia
      (43.5 * 103 +/- 1.1 * 103 U/L). The TAC concentrations (P = 0.15) and urinary F2 
      isoprostanes (P = 0.73) did not significantly differ between groups. CONCLUSIONS
      AND CLINICAL IMPORTANCE: Glutathione peroxidase activity was significantly
      decreased in anemic dogs indicating oxidative stress. Additional studies are
      warranted to determine if antioxidant supplementation would improve survival and
      overall outcome as part of a therapeutic regimen for anemic dogs.

PMID- 29031030
TI  - Ectopic Bone as a Nidus for Calcium Oxalate Urocystolithiasis in a Cat.
AB  - A 7-year-old female spayed domestic shorthair cat was referred to the urology
      service for nonsurgical urocystolith removal. A urolith was attached to the
      urothelium by ectopic bone. Interventional removal without surgery was
      successful. Follow-up evaluation 3 years after urolith removal revealed recurrent
      uroliths, bladder wall mineralization, and marked renal mineralization. This case
      illustrates the metaplastic potential of the urothelium and that ectopic bone
      should be included among the pathological factors that promote lithogenesis.

PMID- 29031031
TI  - RiceAntherNet: a gene co-expression network for identifying anther and pollen
      development genes.
AB  - In plants, normal anther and pollen development involves many important
      biological events and complex molecular regulatory coordination. Understanding
      gene regulatory relationships during male reproductive development is essential
      for fundamental biology and crop breeding. In this work, we developed a rice gene
      co-expression network for anther development (RiceAntherNet) that allows
      prediction of gene regulatory relationships during pollen development.
      RiceAntherNet was generated from 57 rice anther tissue microarrays across all
      developmental stages. The microarray datasets from nine rice male sterile
      mutants, including msp1-4, ostdl1a, gamyb-2, tip2, udt1-1, tdr, eat1-1, ptc1 and
      mads3-4, were used to explore and test the network. Among the changed genes,
      three clades showing differential expression patterns were constructed to
      identify genes associated with pollen formation. Many of these have known roles
      in pollen development, for example, seven genes in Clade 1 (OsABCG15, OsLAP5,
      OsLAP6, DPW, CYP703A3, OsNP1 and OsCP1) are involved in rice pollen wall
      formation. Furthermore, Clade 1 contained 12 genes whose predicted orthologs in
      Arabidopsis have been reported as key during pollen development and may play
      similar roles in rice. Genes in Clade 2 are expressed earlier than Clade 1
      (anther stages 2-9), while genes in Clade 3 are expressed later (stages 10-12).
      RiceAntherNet serves as a valuable tool for identifying novel genes during plant
      anther and pollen development. A website is provided
      (https://www.cpib.ac.uk/anther/riceindex.html) to present the expression profiles
      for gene characterization. This will assist in determining the key relationships
      between genes, thus enabling characterization of critical genes associated with
      anther and pollen regulatory networks.

PMID- 29031032
TI  - The Frequency and Clinical Implications of Bacteriuria in Chronically Paralyzed
      Dogs.
AB  - BACKGROUND: Paralysis is a known risk factor for urinary tract infections (UTI),
      sepsis, and death in paralyzed people, but there are no data available on
      diagnostic criteria for UTI versus bacteriuria, their frequency, or clinical
      implications in chronically paralyzed dogs. HYPOTHESIS/OBJECTIVES: That
      chronically paralyzed dogs suffer frequent bacteriuria causing reduced duration
      of survival. We documented the frequency of bacteriuria, associated clinical
      signs, and survival rate in chronically paralyzed dogs. ANIMALS: Forty-seven
      client-owned dogs paralyzed with no pelvic limb pain perception for >3 months and
      at least one urine culture (UC) performed. METHODS: Retrospective, observational
      study. Medical records of dogs meeting inclusion criteria were reviewed for
      results of UC, urinalysis, and clinical signs. Outcome was compared between dogs
      with and without bacteriuria. RESULTS: Thirty-five of 47 dogs had at least 1
      positive UC, and 13 had recurrent bacteriuria. Rectal temperature and urinalysis
      results were extracted from records. Fever was present at time of UC in 5 of 68
      observations, 2 with and 3 without bacteriuria. Pyuria was significantly
      associated with positive cultures (P < 0.001), cloudiness was not (P = 0.076).
      Survival data in 35 dogs (8 dead) showed no association between bacteriuria and
      survival (P = 0.69). CONCLUSIONS AND CLINICAL IMPORTANCE: Bacteriuria is common
      in paralyzed dogs but does not cause fever; diagnostic criteria of UTI are
      unclear. We did not detect an association of bacteriuria with survival, but this
      needs further confirmation.

PMID- 29031033
TI  - An Arabidopsis divergent pumilio protein, APUM24, is essential for embryogenesis
      and required for faithful pre-rRNA processing.
AB  - Pumilio RNA-binding proteins are largely involved in mRNA degradation and
      translation repression. However, a few evolutionarily divergent Pumilios are also
      responsible for proper pre-rRNA processing in human and yeast. Here, we describe
      an essential Arabidopsis nucleolar Pumilio, APUM24, that is expressed in tissues
      undergoing rapid proliferation and cell division. A T-DNA insertion for APUM24
      did not affect the male and female gametogenesis, but instead resulted in a
      negative female gametophytic effect on zygotic cell division immediately after
      fertilization. Additionally, the mutant embryos displayed defects in cell
      patterning from pro-embryo through globular stages. The mutant embryos were
      marked by altered auxin maxima, which were substantiated by the mislocalization
      of PIN1 and PIN7 transporters in the defective embryos. Homozygous apum24 callus
      accumulates rRNA processing intermediates, including uridylated and adenylated
      5.8S and 25S rRNA precursors. An RNA-protein interaction assay showed that the
      histidine-tagged recombinant APUM24 binds RNAin vitro with no apparent
      specificity. Overall, our results demonstrated that APUM24 is required for rRNA
      processing and early embryogenesis in Arabidopsis.

PMID- 29031034
TI  - [Potential of Using Vitamin D as an Adjuvant Treatment of Malignant Melanoma].
AB  - The incidence of malignant melanoma worldwide continues to grow despite the
      enormous advances in topical and systemic therapy. This increase is recorded
      regularly even in countries where, as a result of public health campaigns,
      dermatological examination and subsequent treatment have become more frequent.
      However, there have been reports of a stable or even decreasing mortality rate
      that seem to contradict the objective increase in its incidence. The well-known
      risk factors for malignant melanoma include sunburns and occasional sunbathing,
      whereas regular sunbathing is associated with a lower incidence. Besides DNA
      damage, exposure to the sun also results in the synthesis of vitamin D
      (cholecalciferol) in the skin, which contributes to over 90% of circulating
      Calcidiol (25 (OH) D) in serum. Current cultural norms (dressing, working
      indoors, avoiding sun exposure, and dietary choices) affect the serum vitamin D
      level, resulting in severely low serum levels of vitamin D in some sectors of
      todays society. Emerging data suggests that mild, unprotected exposure to UV
      radiation or dietary supplementation with oral vitamin D can reduce cancer
      mortality. Supplementation with vitamin D or alternatively UV exposure may be
      regarded as an adjuvant for the treatment of many types of tumors (e.g. tumors of
      the colon, prostate, and breast). The effect of vitamin D on malignant melanoma
      may be due to its non-calcemic systemic effects. Additionally, vitamin D may have
      more pronounced effects locally in the skin because of the unique ability of
      keratinocytes to synthesize the active form of vitamin D.Key words: malignant
      melanoma - vitamin D - adjuvant treatment therapy - clinical oncology The authors
      declare they have no potential conflicts of interest concerning drugs, products,
      or services used in the study. The Editorial Board declares that the manuscript
      met the ICMJE recommendation for biomedical papers.Submitted: 7. 10.
      2016Accepted: 26. 7. 2017.

PMID- 29031035
TI  - [Controversy in the Postoperative Treatment of Low-grade Gliomas].
AB  - BACKGROUND: The optimal treatment for low-grade gliomas remains controversial.
      Neurosurgery, radiotherapy, and chemotherapy are the main treatment options.
      Despite advances in oncology, there are still a lot of uncertainties, and the
      optimal sequences, combinations, and timings of these procedures have not yet
      been optimized. It is still unclear whether temozolomide can replace effective,
      but toxic PCV chemotherapy (procarbazine, lomustine, vincristine) and whether
      temozolomide can be used upfront alone instead of radiotherapy alone. Mature
      results from phase III trials (CODEL, EORTC 22033-26033) will provide answers to
      these questions. Correlative analyses of survival data and molecular marker
      findings (1p/19q codeletion, IDH1/2 mutation, and MGMT promoter methylation
      status) are essential. Due to slow progressive nature of the disease, all
      clinical trials with low-grade gliomas are complicated by the need for long-term
      follow-up to obtain valid mature data, which makes any new treatment procedures
      or developments in basic research developed during the course of closed clinical
      trials difficult to apply in daily clinical practice. An example is the recently
      published RTOG 9802 study evaluating the role of adjuvant PCV in combination with
      radiotherapy for the treatment of high-risk low-grade glioma patients where the
      recruitment of patients was initiated almost two decades ago. Health-related
      quality of life after treatment of patients with expected long-term survival is
      also very important and its maintenance is currently the focus of considerable
      interest. AIM: The main objective of the present review is to summarize the
      results of key clinical trials and highlight controversial issues that could have
      an impact on future daily practice. Another aim is to discuss these issues in the
      light of newly established molecular markers from the new 2016 WHO Classification
      of Tumors of the Central Nervous System.Key words: glioma - astrocytoma -
      radiotherapy - temozolomide - PCV - cognition This work was supported by MH CZ -
      RVO (MMCI, 00209805) and by project of the Ministry of Education, Youths and
      Sports of the Czech Republic CEITEC 2020 (LQ1601). The authors declare they have
      no potential conflicts of interest concerning drugs, products, or services used
      in the study. The Editorial Board declares that the manuscript met the ICMJE
      recommendation for biomedical papers.Submitted: 21. 2. 2017Accepted: 20. 3. 2017.

PMID- 29031036
TI  - [The Role of Chemotherapy in the Treatment of Low-grade Gliomas].
AB  - BACKGROUND: The standard postsurgical options for low-grade gliomas include
      watchful waiting or radiotherapy depending on the risk factors for recurrence.
      The use of chemotherapy for the treatment of this disease is generally
      controversial, although the recently published results of the first of two large
      randomized phase III clinical trials (RTOG 9802 a EORTC 22033-26033), focusing on
      the evaluation of chemotherapy for the upfront treatment of newly diagnosed low
      grade gliomas, are reassuring in this respect. The long-term results of a RTOG
      9802 comparing radiotherapy alone with radiotherapy and six cycles of adjuvant
      PCV chemotherapy (procarbazine, lomustine, vincristine) in patients with high
      risk low-grade gliomas will probably have an impact on daily clinical practice.
      The increase in median overall survival from 7.8 years to 13.3 years, mainly for
      patients with oligodendrogliomas, is unprecedented, but the toxicity of PCV is
      too high and molecular marker analysis remains inadequate. It is still unclear
      whether less toxic temozolomide can replace PCV and whether temozolomide can be
      used upfront alone instead of with radiotherapy. This question is addressed by
      the ongoing EORTC 22033-26033 study. The preliminary results show no significant
      difference in progression-free survival between patients receiving radiotherapy
      and those receiving temozolomide alone. Treatment with temozolomide was not
      associated with an improvement in cognitive function compared with treatment with
      radiotherapy. Despite limited follow-up, the study clearly confirmed the
      importance of molecular characterization of low-grade gliomas, as currently
      defined in the new 2016 WHO Classification of Tumors of the Central Nervous
      System. AIM: The aim of the review is to summarize available information from
      listed key clinical trials of chemotherapy for low-grade gliomas and draw
      attention to unresolved issues concerning the use of chemotherapy for the
      treatment of this disease.Key words: glioma - astrocytoma - chemotherapy - PCV -
      temozolomide - RTOG 9802 This work was supported by MH CZ - RVO (MMCI, 00209805)
      and by project of the Ministry of Education, Youths and Sports of the Czech
      Republic CEITEC 2020 (LQ1601). The authors declare they have no potential
      conflicts of interest concerning drugs, products, or services used in the study.
      The Editorial Board declares that the manuscript met the ICMJE recommendation for
      biomedical papers.Submitted: 21. 2. 2017Accepted: 20. 3. 2017.

PMID- 29031037
TI  - [Evaluation of Anti-cancer Therapies with Reimbursement Limited to Comprehensive
      Cancer Centres Using the European Society for Medical Oncology Magnitude of
      Clinical Benefit Scale].
AB  - BACKGROUND: The costs of oncology treatments are increasing, due to the rising
      prevalence of malignant diseases and the introduction of expensive novel anti
      cancer agents. The new European Society for Clinical Oncology (ESMO) has recently
      developed a new parametric system to evaluate the clinical benefit of drugs. The
      Magnitude of Clinical Benefit Scale (ESMO-MCBS) compares the contribution of a
      novel drug based on overall and progression-free survival and quality of life
      with those of current treatment options. MATERIAL AND METHODS: An expert group of
      the Czech Oncological Society conducted an assessment based on published data and
      an ESMO-MCBS methodology for antineoplastic agents used for the treatment of
      solid tumors with limited reimbursement to Comprehensive Cancer Centers. We
      evaluated drugs categorized as "S" that were eligible for public health insurance
      as of January 1, 2017. RESULTS AND CONCLUSION: The ESMO-MCBS score is a promising
      new parameter for the evaluation of new anticancer drugs. The ESMO-MCBS method
      for assessing the clinical benefit of drugs is simple, robust, and reproducible.
      The advantage of the assessment is that it is not based on a single index but
      rather combines several dimensions of drug performance. This parameter will be
      gradually added to Czech cancer guidelines. Scores obtained in the majority of
      cases correspond to the observed benefit of a drug in routine clinical
      practice.Key words: tumors - farmacotherapy - assesment study as a subject -
      survival - protocols of anti-cancer therapy The authors declare they have no
      potential conflicts of interest concerning drugs, products, or services used in
      the study. The Editorial Board declares that the manuscript met the ICMJE
      recommendation for biomedical papers.Submitted: 3. 5. 2017Accepted: 20. 6. 2017.

PMID- 29031038
TI  - Isocitrate Dehydrogenase Mutations are Better Prognostic Marker than O6
      methylguanine-DNA Methyltransferase Promoter Methylation in Glioblastomas - a
      Retrospective, Single-centre Molecular Genetics Study of Gliomas.
AB  - BACKGROUND: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are a
      promising prognostic biomarker of gliomas. The purpose of our study was to
      examine the clinical prognostic properties of IDH1/2 mutations in a glioma
      patient cohort from the Czech Republic using an improved platform for simple and
      reliable IDH genotyping. MATERIAL AND METHODS: We retrospectively analyzed a
      group of 145 glioma patients by testing for the three most frequent IDH
      mutations, IDH1 R132H, IDH1 R132C, and IDH2 R172K, through the competitive
      amplification of differentially melting amplicons (CADMA) polymerase chain
      reaction (PCR). O6-methylguanine-DNA methyltransferase (MGMT) promoter
      methylation, copy number of EGFR, p53, RB1, MDM2, CDKN2A genes, and deletions in
      1p, 19q and 10p chromosomal regions were also analyzed and correlated with
      clinical characteristics. RESULTS: Of 145 gliomas, 36 harbored IDH1 R132H
      mutation and 1 IDH1 R132C mutation. We did not detect any IDH2 R172K mutation.
      IDH1 mutations were positively associated with MGMT methylation (OR 3.08, 95% CI
      1.387-7.282; p = 0.007), 1p/19q co-loss (OR 8.85, 95% CI 2.367-42.786; p = 0.002)
      and negatively associated with epidermal growth factor receptor amplification (OR
      0.12, 95% CI 0.019-0.437; p = 0.006) and 10p loss (OR 0.09, 95% CI 0.005-0.436; p
      = 0.019). The overall survival of IDH-mutant was 25 months, but only 9 months in
      IDH-wild type gliomas (p = 0.035); at the same time, survival associated with
      methylated vs. unmethylated MGMT promoter did not significantly differ (p =
      0.166). CONCLUSION: Despite IDH1 mutations being closely associated with MGMT
      methylation in glioma patients, IDH1 mutations in glioblastoma patients are
      stronger marker of overall survival than MGMT methylation and should be the
      marker of choice, especially when using genotyping by CADMA PCR.Key words:
      isocitrate dehydrogenase - polymerase chain reaction - glioma - glioblastoma.

PMID- 29031039
TI  - The Anti-apoptotic Mechanism of Metformin Against Apoptosis Induced by Ionizing
      Radiation in Human Peripheral Blood Mononuclear Cells.
AB  - BACKGROUND: In a previous article, we showed that metformin (MET) can reduce
      ionizing radiation (IR) induced apoptosis in human peripheral blood mononuclear
      cells. However, the anti-apoptotic mechanism of MET against IR remains unclear.
      The present study attempts to investigate the mechanism of action of MET in
      limiting X-ray induced apoptosis in human peripheral blood mononuclear cells.
      MATERIAL AND METHODS: Mononuclear cells were treated with MET for 2 hours and
      irradiated with 6 MV X-rays. The gene expression levels of BAX, CASP3 and BCL2
      were determined 24 hours post irradiation using real time quantitative polymerase
      chain reaction (qPCR) technique. Furthermore, the protein levels of BAX, CASP3
      and BCL2 were analyzed by Western blotting assay. RESULTS: Radiation exposure
      increased the expressions of BAX and CASP3 genes, and decreased the expression of
      BCL2 gene in mononuclear cells. Conversely, an increase in BCL2 gene expression
      along with a decrease in BAX and CASP3 genes expression was observed in MET plus
      irradiated mononuclear cells. It was found that radiation increased BAX/BCL2
      ratio, while MET pretreatment reduced these ratios. Also, treatment with MET
      without irradiation did not change the expressions of BAX, CASP3 and BCL2 genes.
      On the other hand, downregulated expression of BCL2 protein and upregulated
      expressions of BAX and CASP3 proteins were found in 2 Gy irradiated mononuclear
      cells, while pretreatment with MET significantly reversed this tendency.
      CONCLUSION: These results suggest that MET can protect mononuclear cells against
      apoptosis induced by IR through induction of cellular anti-apoptotic
      signaling.Key words: ionizing radiation - metformin - apoptosis - genes -
      proteins - blood cells.

PMID- 29031040
TI  - [Treatment Refusal in Pediatric Oncology].
AB  - BACKGROUND: Pediatric oncologists are often faced with situations in which
      parents or guardians refuse recommended treatment for curable childhood cancer.
      Deciding how to proceed in such situations is an ethical dilemma. The aim of this
      article is to consider optimal approaches when parents are strongly against
      oncological treatment, potentially compromising their childrens rights for health
      care and to the chance for cure. CASES: In this paper, we report two cases of
      treatment refusal from our department and the impact of such decisions on the
      children themselves. Case no. 1 describes a child with retinoblastoma whose
      parents refused standard treatment in order to seek alternative treatment abroad.
      Case no. 2 describes a patient with a primary lymphoma of bone who received
      treatment by a court order after parental refusal. CONCLUSION: When parents
      refuse a treatment for potentially curable cancer, the medical team often focuses
      on the certainty of death without treatment. In the background, there is a
      smaller but still significant risk that - even if the treatment is eventually
      accepted or compelled - the child will still die from treatment-related
      complications or refractory disease, possibly with considerable suffering. The
      reasons for refusing a treatment vary. The entire medical team is tasked with
      trying to respectfully understand the reasoning behind the parents unwillingness
      to accept the treatment, in order to address all possible misunderstandings and
      to propose solutions that could be acceptable for the parents. In some situations
      however, it is necessary to resolve the dilemma by legal means in order to
      protect the life of the child.Key words: oncology - ethics - decision making -
      treatment refusal - legal guardians The authors declare they have no potential
      conflicts of interest concerning drugs, products, or services used in the study.
      The Editorial Board declares that the manuscript met the ICMJE recommendation for
      biomedical papers.Submitted: 7. 8. 2017Accepted: 7. 9. 2017.

PMID- 29031041
TI  - Concept Analysis of Growth Failure in Preterm Infants in the NICU.
AB  - Growth failure has not been consistently defined for preterm infants, which
      contributes to unclear clinical guidelines for optimal growth and development.
      Therefore, the purpose of this concept analysis was to identify all uses and
      attributes of the concept, present model and contrary cases, identify antecedents
      and consequences, define empirical referents, and provide an operational
      definition of growth failure among preterm infants in the NICU.

PMID- 29031043
TI  - Comment on "Sphincter-Sparing Excision and Reconstruction Using Facial Artery
      Perforator Flaps for Lower Lip Carcinoma" by Aksam et al.

PMID- 29031042
TI  - Humoral and cellular immune response of mice challenged with Yersinia pestis
      antigenic preparations.
AB  - OBJECTIVES: The plague, which is an infectious disease caused by Yersinia pestis,
      still threatens many populations in several countries. The worldwide increase in
      human plague cases and the potential use of the bacteria as a biological weapon
      reinforce the need to study the immunity that is induced by potential vaccine
      candidates. To determine the immunogenicity of antigenic preparations based on
      the F1 protein and the total extract from Y. pestis, we assessed the role of
      these antigens in inducing an immune response. METHODS: The immunogenicity of
      antigenic preparations based on the Y. pestis (YP) total extract and the Y.
      pestis fraction 1 capsular antigen protein (F1) was determined in Swiss-Webster
      mice immunized with 40MUg or 20MUg for each preparation. Immunophenotyping was
      performed by flow cytometry. RESULTS: Animals immunized with the YP total extract
      did not elicit detectable anti-F1 antibodies (Ab) in the
      hemaglutination/inhibition (HA/HI) test. Animals immunized with 40MUg or 20MUg of
      the F1 protein produced anti-F1 Abs, with titres ranging from 1/16 to 1/8132. The
      average of CD3+-CD4+ and CD3+-CD8+ T cells did not differ significantly between
      the groups. Neither YP total extract nor F1 protein induced a significant
      expression of IFN-gamma and IL-10 in CD4+ T lymphocytes. In addition, F1 failed
      to induce IFN-gamma expression in CD8+ T cells, unlike the YP total extract.
      CONCLUSION: The results showed that F1 protein is not an immunogenic T cell
      antigen, although the YP total extract (40MUg dose) favoured CD8+ T cell-mediated
      cellular immunity.

PMID- 29031044
TI  - The archaic roles of the lamprey NF-kappaB (lj-NF-kappaB) in innate immune
      responses.
AB  - The nuclear factor-kappa B (NF-kappaB) is a pleiotropic transcription factor
      regulating the expression of genes involved in various biological processes
      including the immune response and inflammation. Lamprey is regarded as a key
      species to provide meaningful clues for understanding the evolution of immune
      system; nevertheless, no information about lamprey NF-kappaB is reported. Thus,
      we have characterized a NF-kappaB homolog in lamprey (lj-NF-kappaB) for the
      deeper understanding of the role it played in lamprey immune system. The sequence
      and 3D structure analyses demonstrate that lj-NF-kappaB contained a Rel homology
      domain (RHD) and seven ankyrin repeats domains (ANKs), which would exhibit
      functional similarities to NF-kappaB superfamily proteins. This hypothesis was
      further proved by experiments. We found that the RHD of lj-NF-kappaB could
      interact with a mammalian kappaB response element, translocate to the nucleus to
      modulate gene (IL-6, IL-1beta and TNF-alpha) expression, and the nuclear
      localization signals (NLS) was essential for the nuclear translocation.
      Furthermore, the ANKs of lj-NF-kappaB are the inhibition signal for the RHD of lj
      NF-kappaB. The present results allow us to surmise that the lj-NF-kappaB should
      play a key role in immune response of lamprey, and the function of NF-kappaB has
      been maintained during evolution.

PMID- 29031046
TI  - Contributors to young drivers' driving styles - A comparison between Israel and
      Queensland.
AB  - Among the numerous factors that contribute to young novice drivers' driving
      styles, personality characteristics, sociodemographic variables, family
      atmosphere, and friends' norms are known to have an important impact. However,
      cross-cultural comparisons are relatively rare in the safety literature
      concerning young drivers. This study aimed at comparing young drivers from Israel
      and Queensland (Australia) and examining the contribution of personality,
      sociodemographic, family and friends' aspects to their driving styles (reckless
      and careless; hostile and angry; anxious; patient and careful). More
      specifically, this study examined the associations between young drivers' driving
      style and their perceptions of separation-individuation, the family climate for
      road safety, and the safe driving climate among friends. We also examined
      sociodemographic and driving history variables such as gender, the marital status
      of parents, and personal exposure to traffic crashes. The study consisted of two
      samples of male and female young drivers (age 17-22) from Israel (n=160) and
      Queensland (n=160), who completed a set of valid and reliable self-report
      questionnaires. Findings indicate that in general, maladaptive driving styles are
      associated with lower family tendency to engage in promoting road safety, higher
      pressure and costs of driving with peers, and unhealthier separation
      individuation aspects. The opposite is observed for the patient and careful
      driving style that relates to higher engagement of the family in road safety,
      lower pressure from friends, and healthier separation-individuation. Some
      differences were found regarding specific styles between the two samples. In
      addition, women scored lower than men in the reckless and careless style, and
      higher (in the Israeli sample) in the anxious as well as the patient and careful
      styles. Overall, similarities in the associations between the study variables in
      the samples exceed the differences, and the importance of examining variables on
      multi-levels when referring to young drivers' driving styles, is confirmed. The
      findings attest to the universal utility of the MDSI, together with the
      understanding that only a wider examination of personal and environmental
      contributors enables true insights into the complex behavior of driving among
      young drivers.

PMID- 29031045
TI  - Structural characterization of the Man5 glycoform of human IgG3 Fc.
AB  - Immunoglobulin G (IgG) consists of four subclasses in humans: IgG1, IgG2, IgG3
      and IgG4, which are highly conserved but have unique differences that result in
      subclass-specific effector functions. Though IgG1 is the most extensively studied
      IgG subclass, study of other subclasses is important to understand overall immune
      function and for development of new therapeutics. When compared to IgG1, IgG3
      exhibits a similar binding profile to Fcgamma receptors and stronger activation
      of complement. All IgG subclasses are glycosylated at N297, which is required for
      Fcgamma receptor and C1q complement binding as well as maintaining optimal Fc
      conformation. We have determined the crystal structure of homogenously
      glycosylated human IgG3 Fc with a GlcNAc2Man5 (Man5) high mannose glycoform at
      1.8A resolution and compared its structural features with published structures
      from the other IgG subclasses. Although the overall structure of IgG3 Fc is
      similar to that of other subclasses, some structural perturbations based on
      sequence differences were revealed. For instance, the presence of R435 in IgG3
      (and H435 in the other IgG subclasses) has been implicated to result in IgG3
      specific properties related to binding to protein A, protein G and the neonatal
      Fc receptor (FcRn). The IgG3 Fc structure helps to explain some of these
      differences. Additionally, protein-glycan contacts observed in the crystal
      structure appear to correlate with IgG3 affinity for Fcgamma receptors as shown
      by binding studies with IgG3 Fc glycoforms. Finally, this IgG3 Fc structure
      provides a template for further studies aimed at engineering the Fc for specific
      gain of function.

PMID- 29031047
TI  - Reducing the threat of wildlife-vehicle collisions during peak tourism periods
      using a Roadside Animal Detection System.
AB  - Roadside Animal Detection Systems (RADS) aim to reduce the frequency of wildlife
      vehicle collisions. Unlike fencing and wildlife passages, RADS do not attempt to
      keep animals off the road; rather, they attempt to modify driver behavior by
      detecting animals near the road and warning drivers with flashing signs. A RADS
      was installed in Big Cypress National Park (Florida, USA) in 2012 in response to
      an increased number of Florida panther mortalities. To assess driver response, we
      measured the speed of individual cars on the road when the RADS was active
      (flashing) and inactive (not flashing) during the tourist season (November-March)
      and the off-season (April-October), which vary dramatically in traffic volume. We
      also used track beds and camera traps to assess whether roadside activity of
      large mammal species varied between seasons. In the tourist season, the
      activation of the RADS caused a significant reduction in vehicle speed. However,
      this effect was not observed in the off-season. Track and camera data showed that
      the tourist season coincided with peak periods of activity for several large
      mammals of conservation interest. Drivers in the tourist season generally drove
      faster than those in the off-season, so a reduction in speed in response to the
      RADS is more beneficial in the tourist season. Because traffic volume and
      roadside activity of several species of conservation interest both peak during
      the tourist season, our study indicates that the RADS has the potential to reduce
      the number of accidents during this period of heightened risk.

PMID- 29031048
TI  - Trends in perinatal health in metropolitan France from 1995 to 2016: Results from
      the French National Perinatal Surveys.
AB  - OBJECTIVE: To study trends in the main indicators of perinatal health, medical
      practices and risk factors in France since 1995. POPULATION AND METHOD: All live
      births during one week in 1995 (n=13,318), 2003 (n=14,737), 2010 (n=14,903) and
      2016 (n=13,384). Data were from interviews of women in postpartum wards and from
      medical records and were compared between years. RESULTS: Between 1995 and 2016,
      maternal age and body mass index increased steadily. Pregnancies that occurred
      with use of contraception increased from 7.4% in 2010 to 9.3% in 2016. Smoking
      during pregnancy (16.6%) did not decrease since 2010. The frequency of more than
      three ultrasounds during pregnancy was 48.5% in 1995 and 74.7% in 2016.
      Deliveries in large public hospitals increased steadily. The caesarean section
      rate has been relatively stable since 2003 (20.4% in 2003, 21.1% in 2010 and
      20.4% in 2016). The rate of induction of labour was 22% in 2010 and 2016.
      Overall, 83.8% of women had epidural analgesia/anaesthesia in 2016. Rates of pre
      term birth in 2016 ranged from 7.5% among all live births to 6.0% among live born
      singletons; for singletons, this rate increased steadily from 1995 to 2016,
      whereas there was no clear trend for low birth weight. Exclusive breastfeeding
      decreased from 60.3% in 2010 to 52.2% in 2016. CONCLUSION: Routine national
      perinatal surveys highlight successful policies and recommendations but also
      point out some health indicators, practices, preventive behaviours and risk
      factors that need special attention.

PMID- 29031050
TI  - Paraquat affects mitochondrial bioenergetics, dopamine system expression, and
      locomotor activity in zebrafish (Danio rerio).
AB  - The dipyridyl herbicide paraquat induces oxidative stress in cells and is
      implicated in adult neurodegenerative diseases. However, less is known about
      paraquat toxicity in early stages of vertebrate development. To address this gap,
      zebrafish (Danio rerio) embryos were exposed to 1, 10 and 100 MUM paraquat for 96
      h. Paraquat did not induce significant mortality nor deformity in embryos and
      larvae, but it did accelerate time to hatch. To evaluate whether mitochondrial
      respiration was related to earlier hatch times, oxygen consumption rate was
      measured in whole embryos. Maximal respiration of embryos exposed to 100 MUM
      paraquat for 24 h was reduced by more than 70%, suggesting that paraquat
      negatively impacts mitochondrial bioenergetics in early development. Based upon
      this evidence for mitochondrial dysfunction, transcriptional responses of
      oxidative stress- and apoptosis-related genes were measured. Fish exposed to 1
      MUM paraquat showed higher expression levels of superoxide dismutase 2, heat
      shock protein 70, Bcl-2-associated X protein, and B-cell CLL/lymphoma 2a compared
      to control fish. No differences among groups were detected in larvae exposed to
      10 and 100 MUM paraquat, suggesting a non-monotonic response. We also measured
      endpoints related to larval behavior and dopaminergic signaling as paraquat is
      associated with degeneration of dopamine neurons. Locomotor activity was
      stimulated with 100 MUM paraquat and dopamine transporter and dopamine receptor 3
      mRNA levels were increased in larvae exposed to 1 MUM paraquat, interpreted to be
      a compensatory response at lower concentrations. This study improves mechanistic
      understanding into the toxic actions of paraquat on early developmental stages.

PMID- 29031049
TI  - Heart valve scaffold fabrication: Bioinspired control of macro-scale morphology,
      mechanics and micro-structure.
AB  - Valvular heart disease is currently treated with mechanical valves, which benefit
      from longevity, but are burdened by chronic anticoagulation therapy, or with
      bioprosthetic valves, which have reduced thromboembolic risk, but limited
      durability. Tissue engineered heart valves have been proposed to resolve these
      issues by implanting a scaffold that is replaced by endogenous growth, leaving
      autologous, functional leaflets that would putatively eliminate the need for
      anticoagulation and avoid calcification. Despite the diversity in fabrication
      strategies and encouraging results in large animal models, control over
      engineered valve structure-function remains at best partial. This study aimed to
      overcome these limitations by introducing double component deposition (DCD), an
      electrodeposition technique that employs multi-phase electrodes to dictate valve
      macro and microstructure and resultant function. Results in this report
      demonstrate the capacity of the DCD method to simultaneously control scaffold
      macro-scale morphology, mechanics and microstructure while producing fully
      assembled stent-less multi-leaflet valves composed of microscopic fibers. DCD
      engineered valve characterization included: leaflet thickness, biaxial
      properties, bending properties, and quantitative structural analysis of multi
      photon and scanning electron micrographs. Quasi-static ex-vivo valve coaptation
      testing and dynamic organ level functional assessment in a pressure pulse
      duplicating device demonstrated appropriate acute valve functionality.

PMID- 29031051
TI  - 17beta-Estradiol induces cyto-genotoxicity on blood cells of common carp
      (Cyprinus carpio).
AB  - 17beta-Estradiol, a natural hormone present at high concentrations in aquatic
      ecosystems, affects and modifies endocrine function in animals. In recent years
      research workers have expressed concern over its potential effects on aquatic
      organisms; however, little is known about its capacity to induce genetic damage
      or the pro-apoptotic effects of such damage on fish. Therefore, this study aimed
      to evaluate 17beta-estradiol-induced cyto-genotoxicity in blood cells of the
      common carp Cyprinus carpio exposed to different concentrations (1 ng, 1 MUg and
      1 mg L-1). Peripheral blood samples were collected and evaluated by comet assay,
      micronucleus test, determination of caspase-3 activity and TUNEL assay at 12, 24,
      48, 72 and 96 h of exposure. Increases in frequency of micronuclei, TUNEL
      positive cells and caspase-3 activity were observed, particularly at the highest
      concentration. In contrast, the comet assay detected significant increases at 24
      and 96 h with the 1 MUg and 1 ng L-1 concentrations respectively. The set of
      assays used in the present study constitutes a reliable early warning biomarker
      for evaluating the toxicity induced by this type of emerging contaminants on
      aquatic species.

PMID- 29031052
TI  - Dispersibility and biotransformation of oils with different properties in
      seawater.
AB  - Dispersants are used to remove oils slicks from sea surfaces and to generate
      small oil-droplet dispersions, which may result in enhanced biodegradation of the
      oil. In this study, dispersibility and biodegradation of chemically dispersed
      oils with different physical-chemical properties (paraffinic, naphthenic and
      asphaltenic oils) were compared in natural temperate SW at 13  degrees C. All
      selected oils were chemically dispersible when well-known commercial dispersants
      were used. However, interfacial tension (IFT) studies of the dispersed oils
      showed different IFT properties of the oils at 13  degrees C, and also different
      leaching of the dispersants from oil droplet surfaces. Biodegradation studies of
      the chemically dispersed oils were performed in a carousel system, with initial
      median droplet sizes <30 MUm and oil concentrations of 2.5-2.8 mg/L. During
      biodegradation, oil droplet concentrations were rapidly reduced, in association
      with the emergence of macroscopic 'flocs'. Biotransformation results showed that
      half-lives of semivolatile total extractable organic carbon (TEOC), single target
      2- to 4-ring PAH, and 22 oil compound groups used as input data in the oil spill
      contingency model OSCAR, did not differ significantly between the oils (P >
      0.05), while n-alkanes half-lives differed significantly (P < 0.05).
      Biotransformation was associated with rapid microbial growth in all oil
      dispersions, in association with n-alkane and PAH biotransformation. These
      results have implications for the predictions of biodegradation of oil slicks
      treated with dispersants in temperate SW.

PMID- 29031053
TI  - Enhanced degradation and mineralization of 4-chloro-3-methyl phenol by Zn-CNTs/O3
      system.
AB  - A novel zinc-carbon nanotubes (Zn-CNTs) composite was prepared, characterized and
      used in O3 system for the enhanced degradation and mineralization of chlorinated
      phenol. The Zn-CNTs was characterized by SEM, BET and XRD, and the degradation of
      4-chloro-3-methyl phenol (CMP) in aqueous solution was investigated using Zn
      CNTs/O3 system. The experimental results showed that the rate constant of total
      organic carbon (TOC) removal was 0.29 min-1, much higher than that of only O3
      system (0.059 min-1) because Zn-CNTs/O2 system could generate H2O2 in situ, the
      concentration of H2O2 could reach 156.14 mg/L within 60 min at pH 6.0. The high
      mineralization ratio of CMP by Zn-CNTs/O3 occurred at wide pH range (3.0-9.0).
      The increase of Zn-CNTs dosage or gas flow rate contributed to the enhancement of
      CMP mineralization. The intermediates of CMP degradation were identified and the
      possible degradation pathway was tentatively proposed.

PMID- 29031054
TI  - Magnetic biochar catalyst derived from biological sludge and ferric sludge using
      hydrothermal carbonization: Preparation, characterization and its circulation in
      Fenton process for dyeing wastewater treatment.
AB  - To solve sludge disposal and management problems during dyeing wastewater
      treatment, the produced excess biological sludge and ferric sludge were
      fabricated into a magnetic biochar composite (MBC) under the optimal hydrothermal
      carbonization (HTC) conditions. With ferric sludge mixing, the generated MBC
      contained paramagnetic Fe3O4, showed a smaller diameter of approximately 200 nm,
      a smaller pore size, a larger specific surface area and a higher carbonization
      degree than BC prepared using a single biological sludge process under the same
      HTC conditions. Additionally, biochar and Fe3O4 in the MBC were found to be
      tightly combined through chemical bonding, imparting MBC with its own property of
      magnetic recycling. The stable high Methylene Blue (MB) degradation performance
      in a Fenton reaction after recycling designated it as a good catalyst. The MB
      degradation pathway was proposed based on GC-MS results. When the MBC was used to
      treat actual dyeing wastewater through a Fenton process, the chemical oxygen
      demand (COD) and total organic carbon (TOC) removal efficiencies reached 47 +/-
      3.3% and 49 +/- 2.7%, respectively. Therefore, MBC could be recycled as a
      catalyst in dyeing wastewater treatment. And a methodology is described that
      minimizes the produced sludge and enables sludge internal recycling in a dyeing
      wastewater treatment plant.

PMID- 29031055
TI  - Iron chloride catalysed PCDD/F-formation: Experiments and PCDD/F-signatures.
AB  - Iron chloride is often cited as catalyst of PCDD/F-formation, together with
      copper chloride. Conversely, iron chloride catalysis has been less studied during
      de novo tests. This paper presents such de novo test data, derived from model fly
      ash incorporating iron (III) chloride and established over a vast range of
      temperature and oxygen concentration in the gas phase. Both PCDD/F-output and its
      signature are extensively characterised, including homologue and congener
      profiles. For the first time, a complete isomer-specific analysis is
      systematically established, for all samples. Special attention is paid to the
      chlorophenols route PCDD/F, to the 2,3,7,8-substituted congeners, and to their
      relationship and antagonism.

PMID- 29031056
TI  - Physiological and biochemical responses of wheat (Triticum aestivum L.) seedlings
      to three imidazolium-based ionic liquids in soil.
AB  - Ionic liquids (ILs) are considered environmentally friendly solvents and are
      widely applied in various fields; however, some researchers have noted the
      toxicity of ILs to plants cultivated in nutrient solution. To evaluate the
      toxicities of ILs to wheat seedlings in soil, the natural growth environment of
      plants, a study was performed using three imidazolium-based ionic liquids with
      different anions: 1-octyl-3-methylimidazolium chloride ([C8mim]Cl), 1-octyl-3
      methylimidazolium bromide ([C8mim]Br) and 1-octyl-3-methylimidazolium
      tetrafluoroborate ([C8mim]BF4). After 13 d of exposure to these three ILs at 0,
      100, 200, 400, 600 and 800 mg kg-1 in brown soil, wheat seedlings were randomly
      sampled to evaluate growth (shoot length, root length, pigment content and
      proline content), lipid peroxidation, oxygen species (H2O2 and O2-) and
      activities of the detoxification enzyme glutathione-s-transferase and other
      antioxidant enzymes, including superoxide dismutase, catalase and peroxidase. The
      experimental results showed that all three ILs had inhibitory effects on the
      growth of wheat seedlings and induced the generation of reactive oxygen species,
      which indicated that the wheat seedlings suffered oxidative stress. Moreover,
      antioxidant enzyme activity was enhanced after exposure to [C8mim]Cl, [C8mim]Br
      and [C8mim]BF4, demonstrating that oxidative damage may be the primary underlying
      mechanism of IL toxicity in wheat.

PMID- 29031057
TI  - Arsenic speciation in fish and shellfish from the North Sea (Southern bight) and
      Acu Port area (Brazil) and health risks related to seafood consumption.
AB  - In North Sea and Port Acu (Brazil) coastal areas, high arsenic (As)
      concentrations were observed in water, soil and sediments. Therefore, the impact
      of this contamination on fish and shellfish species bought from local fishermen
      was studied. Total As was assessed with ICP-OES (Brazil) and ICP-MS (North Sea)
      after microwave digestion. Toxic As was assessed with liquid chromatography-ICP
      MS (Brazil) and hydride generation-atomic fluorescence spectrometry (North Sea).
      All analytical methods comply with Quality Assurance/Quality Control procedures.
      Several fish species have average Total As concentrations above 1 MUg g-1 wet
      weight (ww), but the highest concentrations are found in less spotted dogfish,
      lemon sole and whelks from the North Sea, with respectively 50, 49 and 50 MUg g-1
      ww. High Total As concentrations correspond to high Toxic As concentrations,
      except for scallops having increased Toxic As concentrations. Toxic As fractions
      are highest in scallops (almost 10%) but rarely exceeds 2% in all other species.
      Liver samples were only analyzed in ray, dogfish and catfish and their Toxic As
      fractions are between 2 and 4 times higher than in muscle. For a consumption of
      150 g of seafood, only 3 samples exceed the provisional total daily intake of 2
      MUg kg-1 bw, however, cancer risks are non-negligible. Using mean Toxic As
      concentrations for each of the different fish and shellfish species studied,
      Lifetime Cancer Risk values at the actual global seafood consumption rate of 54 g
      day-1 are above 10-4 for whelks, scallops, dogfish, ray and lemon sole.

PMID- 29031058
TI  - Trimethoprim degradation by Fenton and Fe(II)-activated persulfate processes.
AB  - Trimethoprim is a pollutant ubiquitous in the environment due to its extensive
      application, and it cannot be effectively removed by conventional wastewater
      treatment processes. In this study, the Fenton and the Fe(II)-activated
      persulfate processes were employed to degrade trimethoprim in an aqueous
      solution. The results showed that the concentration of persulfate, H2O2 and
      Fe(II) a had significant influence on the degradation of trimethoprim in both
      processes. De-ionized water spiked with trimethoprim resulted in the complete
      degradation of trimethoprim (0.05 mM) by the mineralization of 54.9% of Fenton's
      reagent when the concentrations of H2O2 and Fe(II) were 1 mM and 0.05 mM,
      respectively. In contrast, 73.4% of trimethoprim was degraded by the
      mineralization of 40.5% of the Fe(II)-activated persulfate process when the
      concentration of persulfate and Fe(II) were each 4 mM. Intermediate compounds
      with different m/z were detected for the Fenton and the Fe(II)-activated
      persulfate processes, indicating alternative degradation pathways. In the actual
      wastewater spiked with trimethoprim, the removal efficiency of trimethoprim
      decreased to 35.8% and 43.6%, respectively, for the Fenton and the Fe(II)
      activated persulfate processes. In addition, the decomposition efficiencies for
      hydrogen peroxide and persulfate were 43.8% and 92.5%, respectively, which was
      lower than those in the de-ionized water system. These results demonstrated that
      wastewater components had a negative influence on trimethoprim degradation and
      the decomposition of the oxidants (persulfate and H2O2). In summary, the Fe(II)
      activated persulfate process could be used as an alternative technology for
      treating trimethoprim-containing wastewater.

PMID- 29031059
TI  - Tying up tranylcypromine: Novel selective histone lysine specific demethylase 1
      (LSD1) inhibitors.
AB  - Aberrant expression of lysine specific histone demethylase 1 (LSD1) has been
      increasingly associated with numerous cancer cells and several proof-of-concept
      studies are strongly suggestive of its potential as a druggable target.
      Tranylcypromine (TCP) is an antidepressant originally known to target the
      monoamine oxidases A and B (MAO-A and MAO-B), which are structurally related to
      LSD1. A number of TCP derivatives have been identified as potent LSD1 inhibitors,
      with a handful of them currently being tested in clinical trials. However, thus
      far the majority of structure-activity relationship studies reported on these TCP
      derivatives have been mostly limited to the racemates. In this study, we present
      the SAR data for a novel series of conformationally-restricted TCP-based LSD1
      inhibitors, both in their racemic and enantiomerically pure forms. Compounds 18b
      and 19b were identified as the most potent LSD1 inhibitors within this series,
      possessing excellent selectivity (>10,000-fold) against MAO-A and MAO-B. These
      compounds activated CD86 expression on the human MV4-11 AML cells following 10
      days of exposure, accompanied with the apparent cytotoxicity. Taken together,
      these findings are consistent with the pharmacological inhibition of LSD1 and
      further provide structural insights on the binding modes of these TCP derivatives
      and their enantiomers at the LSD1.

PMID- 29031060
TI  - An insight into the biological activities of heterocyclic-fatty acid hybrid
      molecules.
AB  - Heterocyclic compounds are the interesting core structures for the development of
      new bioactive compounds. Fatty acids are derived from renewable raw materials and
      exhibit various biological activities. Several researchers are amalgamating these
      two bioactive components to yield bioactive hybrid molecules with some desirable
      features. Heterocyclic-fatty acid hybrid derivatives are a new class of
      heterocyclic compounds with a broad range of biological activities and
      significance in the field of medicinal chemistry. Over the last few years, many
      research articles emphasized the significance of heterocyclic-fatty acid hybrid
      derivatives. The present review article focuses the developments in designing and
      biological evaluation of heterocyclic-fatty acid hybrid molecules.

PMID- 29031061
TI  - Crassiflorone derivatives that inhibit Trypanosoma brucei glyceraldehyde-3
      phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase
      (TcTR) and display trypanocidal activity.
AB  - Crassiflorone is a natural product with anti-mycobacterial and anti-gonorrhoeal
      properties, isolated from the stem bark of the African ebony tree Diospyros
      crassiflora. We noticed that its pentacyclic core possesses structural
      resemblance to the quinone-coumarin hybrid 3, which we reported to exhibit a dual
      targeted inhibitory profile towards Trypanosoma brucei glyceraldehyde-3-phosphate
      dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR).
      Following this basic idea, we synthesized a small library of crassiflorone
      derivatives 15-23 and investigated their potential as anti-trypanosomatid agents.
      19 is the only compound of the series showing a balanced dual profile at 10 MUM
      (% inhibitionTbGAPDH = 64% and % inhibitionTcTR = 65%). In phenotypic assay, the
      most active compounds were 18 and 21, which at 5 MUM inhibited Tb bloodstream
      form growth by 29% and 38%, respectively. Notably, all the newly synthesized
      compounds at 10 MUM did not affect viability and the status of mitochondria in
      human A549 and 786-O cell lines, respectively. However, further optimization that
      addresses metabolic liabilities including solubility, as well as cytochromes P450
      (CYP1A2, CYP2C9, CYP2C19, and CYP2D6) inhibition, is required before this class
      of natural product-derived compounds can be further progressed.

PMID- 29031063
TI  - Anticancer properties of 4-thiazolidinone derivatives depend on peroxisome
      proliferator-activated receptor gamma (PPARgamma).
AB  - Peroxisome proliferator-activated receptors (PPARs) play an important role in
      numerous chronic diseases such as diabetes, obesity, atherosclerosis and cancer,
      and PPAR modulators are among the approved drugs and drug-candidates for their
      treatment. The aim of this study was to elucidate the involvement of PPARs in the
      mechanism of cytotoxic and pro-apoptotic action of novel anticancer 4
      thiazolidinone derivatives (Les-2194, Les-3377, Les-3640) and approved 4
      thiazolidinones (Rosiglitazone, Pioglitazone) towards the human squamous
      carcinoma (SCC-15) cell line. Experiments with 4-thiazaolidinone derivatives and
      PPAR-specific siRNA were conducted and PPARalpha, PPARbeta and PPARgamma mRNA
      expression was studied. Moreover, after PPARalpha, PPARbeta and PPARgamma siRNA
      gene silencing, cell viability, cell metabolism and caspase-3 activity were
      measured. The results showed a decrease of mRNA expression of the studied PPARs
      in SCC-15 cells treated with 10 and 50 MUM Les-2194, Les-3377 and Les-3640.
      PPARgamma knockdown protected the cells from the cytotoxic effect of the tested
      compounds (50 MUM). It was established that novel anticancer 4-thiazolidinone
      derivatives act mainly through the PPARgamma pathway in SCC-15 cells. Our results
      suggest that all studied compounds act as PPARs agonists. Interestingly,
      silencing of PPARgamma gene increases the expression of PPARalpha, PPARbeta mRNA
      in SCC-15 cells. The anticancer potential of new studied compounds was more
      expressed as compared to Rosiglitazone and Pioglitazone.

PMID- 29031062
TI  - Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4
      diones as inhibitors of HIV reverse transcriptase-associated RNase H.
AB  - Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated
      ribonuclease H (RNase H) is the only HIV enzymatic function not targeted by
      current antiviral drugs. Although various chemotypes have been reported to
      inhibit HIV RNase H, few have shown significant antiviral activities. We report
      herein the design, synthesis and biological evaluation of a novel N-hydroxy
      thienopyrimidine-2,3-dione chemotype (11) which potently and selectively
      inhibited RNase H with considerable potency against HIV-1 in cell culture.
      Current structure-activity-relationship (SAR) identified analogue 11d as a
      nanomolar inhibitor of RNase H (IC50 = 0.04 MUM) with decent antiviral potency
      (EC50 = 7.4 MUM) and no cytotoxicity (CC50 > 100 MUM). In extended biochemical
      assays compound 11d did not inhibit RT polymerase (pol) while inhibiting
      integrase strand transfer (INST) with 53 fold lower potency (IC50 = 2.1 MUM) than
      RNase H inhibition. Crystallographic and molecular modeling studies confirmed the
      RNase H active site binding mode.

PMID- 29031065
TI  - Synthesis and antibacterial activity of new symmetric polyoxygenated
      dibenzofurans.
AB  - A series of symmetric polyoxygenated dibenzofurans with 2-methylbutyril moieties
      at C-4 and C-6 were obtained from commercial phloroglucinol through a sequence of
      reactions that include monoacylation, iodination, Suzuki-Miyaura coupling,
      oxidative dimerization and cyclization. Some of the compounds obtained were
      active against Gram-positive bacteria, including multiresistant Staphylococcus
      aureus clinical isolates. The dibenzofuran 28 with propyl chains at C-2 and C-8
      exhibited the best antibacterial activity with values comparable to those of the
      natural dibenzofuran achyrofuran. From the obtained results some structure
      activity relationships were outlined.

PMID- 29031064
TI  - Fragment-based approach to identify IDO1 inhibitor building blocks.
AB  - Indoleamine 2,3-dioxygenase 1 (IDO1) is attracting a great deal of interest as
      drug target in immune-oncology being highly expressed in cancer cells and
      participating to the tumor immune-editing process. Although several classes of
      IDO1 inhibitors have been reported in literature and patent applications, only
      few compounds have proved optimal pharmacological profile in preclinical studies
      to be advanced in clinical trials. Accordingly, the quest for novel structural
      classes of IDO1 inhibitors is still open. In this paper, we report a fragment
      based screening campaign that combines Water-LOGSY NMR experiments and microscale
      thermophoresis approach to identify fragments that may be helpful for the
      development of novel IDO1 inhibitors as therapeutic agents in immune-oncology
      disorders.

PMID- 29031066
TI  - Serendipitous discovery of potent human head and neck squamous cell carcinoma
      anti-cancer molecules: A fortunate failure of a rational molecular design.
AB  - Histone deacetylase inhibitors (HDACis) play an important role as valuable drugs
      targeted to cancer therapy: several HDACis are currently being tested in clinical
      trials. Two new potential HDACis 1a and 1d, characterized by the presence of a
      biphenyl-4-sulfonamide group as a connection unit between the N-{4-[(E)-(2
      formylhydrazinylidene)methyl]-3-hydroxyphenyl} and the 2-hydroxy-N
      (trifluoroacetyl)benzamide moiety, respectively, as two zinc-binding group (ZBG),
      have been designed, synthesized and tested for their biological activity.
      Surprisingly, compounds 1a and 12, this last exclusively obtained in place of 1d,
      exhibited a very low HDAC inhibitory activity. A serendipitous assay of these two
      compounds, conducted on three chemoresistant cell lines of head and neck squamous
      cell carcinoma (HNSCC), showed their antiproliferative activity at low nanomolar
      concentrations, better than cisplatin. In vitro, biological assays indicated that
      compounds 1a and 12 are able to increase acetylation of histone H3 and to
      interfere with the PI3K/Akt/mTOR pathway by inducing the accumulation of PTEN
      protein.

PMID- 29031067
TI  - New pyridine derivatives as inhibitors of acetylcholinesterase and amyloid
      aggregation.
AB  - A new series of pyridine derivatives with carbamic or amidic function has been
      designed and synthesized to act as cholinesterase inhibitors. The synthesized
      compounds were tested toward EeAChE and hAChE and toward eqBChE and hBChE. The
      carbamate 8 was the most potent hAChE inhibitor (IC50 = 0.153 +/- 0.016 MUM)
      while the carbamate 11 was the most potent inhibitor of hBChE (IC50 = 0.828 +/-
      0.067 MUM). A molecular docking study indicated that the carbamate 8 was able to
      bind AChE by interacting with both CAS and PAS, in agreement with the mixed
      inhibition mechanism. Furthermore, the carbamates 8, 9 and 11 were able to
      inhibit Abeta42 self-aggregation and possessed quite low toxicity against human
      astrocytoma T67 and HeLa cell lines, being the carbamate 8 the less toxic
      compound on both cell lines.

PMID- 29031068
TI  - Platinum(IV) prodrugs multiply targeting genomic DNA, histone deacetylases and
      PARP-1.
AB  - Several Pt(IV) prodrugs containing SAA, a histone deacetylases inhibitor, were
      designed and prepared for multiply targeting genomic DNA, histone deacetylases
      and PARP-1. The resulting Pt(IV) prodrug had significantly strong
      antiproliferative activity against the tested cancer cell lines, especially SAA1,
      derived from the conjugation of cisplatin and SAA, had potent ability to overcome
      cisplatin resistance. Under the combined action of DNA platination and inhibition
      of HDACs and PARP-1 activity, the cytotoxic activity of SAA1 was 174-fold higher
      than cisplatin against cisplatin-resistant SGC7901/CDDP cancer cells. The
      mechanism of action of SAA1 was preliminarily investigated, in which cellular
      uptake, cell apoptosis and cell cycle arrest as well as western blot analysis
      were made by treating SAA1 with SGC7901/CDDP cells. Besides, HDACs inhibition
      activity and PARP-1 enzyme inhibition of SAA1 were also studied.

PMID- 29031069
TI  - Synthesis and biological evaluation of a Platinum(II)-c(RGDyK) conjugate for
      integrin-targeted photodynamic therapy.
AB  - A cancer-targeting conjugate 4 of a cyclometalated [N,C,N-Pt(II)] complex bearing
      a N^C^N 1,3-di(2-pyridyl)-benzene with c(RGDyK) peptide as guiding molecule was
      designed and synthesized for real-time drug delivery monitoring in cancer cells
      and photodynamic therapy (PDT). This conjugate demonstrates a mild cytostatic
      effect to six cancer cell lines expressing integrins at different extent, while
      possessing promising features for PDT. Conjugate 4 demonstrated rapid cell uptake
      by receptor-mediated endocytosis and efficient generation of 1O2 upon
      irradiation. Incubation of rat bladder cancer cells AY27 with conjugate 4 (50
      MUMU) prior to blue light exposure (5 min) resulted in significant reduction
      (50%) of cell survival compared to control cells as measured by MTT assay post 24
      h after treatment.

PMID- 29031070
TI  - Nature-based molecules combined with rivastigmine: A symbiotic approach for the
      synthesis of new agents against Alzheimer's disease.
AB  - Starting from nature as original source, new potential agents with pleiotropic
      activities have been synthesized and evaluated as neuroprotective agents. In this
      work, novel nature-based hybrids, combining antioxidant motifs with rivastigmine,
      have been designed and synthesized. The biological results revealed that the new
      compounds inhibit both AChE and BuChE. In particular, lipoic acid hybrids LA1,
      LA2, LA3 resulted to be the most potent inhibitors of BuChE showing IC50 values
      ranging from 340 to 378 nM. Analogously, all the compounds were able to inhibit
      the self beta-amyloid1-42 aggregation. The gallic acid hybrid GA2 as well as the
      2-chromonecarboxylic acid hybrids CA1 and CA2 prevented the self-mediated Abeta
      aggregation with percentages of inhibition ranging from 53% to 59%. Finally, some
      of them also show potent neuroprotective effects against glutamate-induced cell
      death and low toxicity in HT22 cells.

PMID- 29031072
TI  - Recent advances in discovery and development of natural products as source for
      anti-Parkinson's disease lead compounds.
AB  - Parkinson's disease (PD) is a common chronic degenerative disease of the central
      nervous system. Although the cause remains unknown, several pathological
      processes and central factors such as oxidative stress, mitochondrial injury,
      inflammatory reactions, abnormal deposition of alpha-synuclein, and cell
      apoptosis have been reported. Currently, anti-PD drugs are classified into two
      major groups: drugs that affect dopaminergic neurons and anti-cholinergic drugs.
      Unfortunately, the existing conventional strategies against PD are with numerous
      side effects, and cannot fundamentally improve the degenerative process of
      dopaminergic neurons. Therefore, novel therapeutic approaches which have a novel
      structure, high efficiency, and fewer side effects are needed. For many years,
      natural products have provided an efficient resource for the discovery of
      potential therapeutic agents. Among them, many natural products possess anti-PD
      properties as a result of not only their wellrecognized anti-oxidative and anti
      inflammatory activities but also their inhibitory roles regarding protein
      misfolding and the regulatory effects of PD related pathways. Indeed, with the
      steady improvement in the technologies for the isolation and purification of
      natural products and the in-depth studies on the pathogenic mechanisms of PD,
      many monomer components of natural products that have anti-PD effects have been
      gradually discovered. In this article, we reviewed the research status of 37
      natural products that have been discovered to have significant anti-PD effects as
      well as their mode of action. Overall, this review may guide the design of novel
      therapeutic drugs in PD.

PMID- 29031071
TI  - Discovery of thienopyrrolotriazine derivatives to protect mitochondrial function
      against Abeta-induced neurotoxicity.
AB  - Recovery of mitochondrial dysfunction has gained increasing attention as an
      alternative therapeutic strategy for Alzheimer's disease (AD). Recent studies
      suggested that the 18 kDa mitochondrial translocator protein (TSPO) has the
      potential to serve as a drug target for the treatment of AD. In this study, we
      generated a structure-based pharmacophore model and virtually screened a
      commercial library, identifying SVH07 as a virtual hit, which contained a
      tricyclic core structure, thieno[2',3':4,5]pyrrolo[1,2-d][1,2,4]triazine group. A
      series of SVH07 analogues were synthesized and their effects on the mitochondrial
      membrane potential and ATP production were determined by using neuronal cells
      under Abeta-induced toxicity. Among these analogues, compound 26 significantly
      recovered mitochondrial membrane depolarization and ATP production. In vitro
      binding assays indicated that SVH07 and 26 showed high affinities to TSPO with
      the IC50 values in a nanomolar range. We believe that compound 26 is a promising
      lead compound for the development of TSPO-targeted mitochondrial functional
      modulators with therapeutic potential in AD.

PMID- 29031073
TI  - Discovery of novel diarylpyrazolylquinoline derivatives as potent anti-dengue
      virus agents.
AB  - A number of diarylpyrazolylquinoline derivatives were synthesized and evaluated
      for their anti-dengue virus (DENV) activity. Among them, 6-fluoro-2-(1-(4
      fluorophenyl)-3- (4-methoxyphenyl)-1H-pyrazol-5-yl)quinoline (11c), 2-[1,3-bis(4
      methoxyphenyl)-1H-pyrazol- 5-yl]-6-fluoroquinoline (12c), and 4-[5-(6
      fluoroquinolin-2-yl)-3-(4-methoxyphenyl)-1H-pyrazol- 1-yl]benzenesulfonamide
      (13c) exhibited approximately 10-folds more active anti-DENV-2 activity (IC50 of
      1.36, 1.09 and 0.81 MUM, respectively) than that of ribavirin (IC50 = 12.61 MUM).
      Compound 13c was also potent inhibited other sero-types of DENV. It reduced DENV
      replication in both viral protein and mRNA levels, and no significant cell
      cytotoxicity was detected, with greater than 50% viability of Huh-7-DV-Fluc cells
      at a concentration of 200 MUM. Furthermore, compound 13c can effectively protect
      mice from DENV infection by reducing disease symptoms and mortality of DENV
      infected mice. It represents a potential antiviral agent to block DENV
      replication in vitro and in vivo. Structural optimization of the initial lead
      compound, 13c, and the detailed molecular mechanism of action are ongoing.

PMID- 29031074
TI  - Synthesis, antiproliferative, anti-tubulin activity, and docking study of new
      1,2,4-triazoles as potential combretastatin analogues.
AB  - Combretastatin A4 (CA4) is a natural product characterized by a powerful
      inhibition of tubulin polymerization and a potential anticancer activity.
      However, therapeutic application of CA4 is substantially hindered due to
      geometric isomerization. In the current study, new cis-restricted Combretastatin
      A4 analogues containing 1,2,4-triazle in place of the olefinic bond were designed
      and synthesized. The synthesized compounds were evaluated for their in vitro
      antiproliferative activity in human hepatocellular carcinoma HepG2 and leukemia
      HL-60 cell lines using MTT assay. Moreover, fourteen compounds were selected and
      tested for their antiproliferative activity by the National Cancer Institute.
      Some of the tested compounds showed moderate activity against sixty cell lines.
      In vitro tubulin polymerization inhibitory activity was evaluated on HepG2 cells.
      The assay revealed that 6a showed a remarkable tubulin inhibition compared to
      CA4. Moreover, the cell cycle analysis revealed significant G2/M cell cycle
      arrest of the analogue 6c in HepG2 cells. Molecular docking combined with AMBER
      based molecular mechanical minimization results showed several noncovalent
      interactions, including van der Waals and hydrogen-bonding with several amino
      acids within the colchicine binding site of beta-subunit of tubulin.

PMID- 29031075
TI  - Discovery of new indomethacin-based analogs with potentially selective
      cyclooxygenase-2 inhibition and observed diminishing to PGE2 activities.
AB  - New ring-extended analogs of indomethacin were designed based on the structure of
      active binding site of both COX-1 and COX-2 isoenzymes and the interaction
      pattern required for selective inhibition of COX-2 to improve its selectivity
      against COX-2. The strategy adopted for designing the new inhibitors involved i)
      ring extension of indomethacin to reduce the possibility of analogs to be
      accommodated into the narrow hydrophobic tunnel of COX-1, ii) deletion of
      carboxylic acid to reduce the possibility of inhibitor to form salt bridge with
      Arg120 and eventually prevent COX-1 inhibition, and iii) introduction of
      methylsulfonyl group to increase the opportunity of the analogs to interact with
      the polar side pocket that's is crucial for inhibition process of COX-2. The
      three series of tetrahydrocarbazoles involving 4, 5, 9, 10 and 12 were
      synthesized in quantitative yields adopting limited number of reaction steps, and
      applying laboratory friendly reaction conditions. In vitro and in vivo assays for
      data profiling the new candidates revealed the significant improvement in the
      potency and selectivity against COX-2 of 6-methoxytetrahydrocarbazole 4 (IC50 =
      0.97 MUmol) to verify the effect of ring extension in comparison to indomethacin
      (IC50 = 2.63 MUmol), and 6-methylsulfonyltetrahydrocarbazole 10a (IC50 = 0.28
      MUmol) to verify the effect of ring extension and introduction of methylsulfonyl
      group. 9-(4-chlorobenzoyl)-6-(methylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4
      one 12a showed the most potential and selective activity against COX-2 (IC50 =
      0.23 MUmol) to be with superior potency to Celecoxib (IC50 = 0.30 MUmol).
      Consistently, 12a was the most active with all the other anti-inflammatory test
      descriptors and its activity in diminishing the PGE2 with the other analogs
      confirmed the elaboration of new class of selective COX-2 inhibitors beyond the
      diarylsulfonamides as a previously common class of selective COX-2 inhibitors.
      Molecular docking study revealed the high binding score of compound 12a (-30.78
      kcal/mol), with less clash contribution (7.2) that is close to indomethacin.
      Also, 12a showed low conformation entropy score (1.40). Molecular dynamic (MD)
      simulation identified the equilibrium of both potential and kinetic energies.

PMID- 29031076
TI  - Synthesis and evaluation of new pyridyl/pyrazinyl thiourea derivatives:
      Neuroprotection against amyloid-beta-induced toxicity.
AB  - Herein, we report synthesis and evaluation of new twenty six small molecules
      against beta amyloid (Abeta)-induced opening of mitochondrial permeability
      transition pore (mPTP) using JC-1 assay which measures the change of
      mitochondrial membrane potential (DeltaPsim). The neuroprotective effect of
      seventeen compounds against Abeta-induced mPTP opening was superior to that of
      the standard Cyclosporin A (CsA). Fifteen derivatives eliciting increased green
      to red fluorescence percentage less than 40.0% were evaluated for their impact on
      ATP production, cell viability and neuroprotection against Abeta-induced neuronal
      cell death. Among evaluated compounds, derivatives 9w, 9r and 9k had safe profile
      regarding ATP production and cell viability. In addition, they exhibited
      significant neuroprotection (69.3, 51.8 and 48.2% respectively). Molecular
      modeling study using CDocker algorithm predicted plausible binding modes
      explaining the elicited mPTP blocking activity. Hence, this study suggests
      compounds 9w, 9r and 9k as leads for further development of novel therapy to
      Alzheimer's disease.

PMID- 29031077
TI  - 4-Quinolone hybrids and their antibacterial activities.
AB  - The emergence and wide-spread of drug-resistant bacteria including multi-drug
      resistant and pan-drug resistant pathogens which are associated with considerable
      mortality, represent a significant global health threat. 4-Quinolones which are
      exemplified by fluoroquinolones are the second largest chemotherapy agents used
      in clinical practice for the treatment of various bacterial infections. However,
      the resistance of bacteria to 4-quinolones develops rapidly and spreads widely
      throughout the world due to the long-term, inappropriate use and even abuse. To
      overcome the resistance and improve the potency, several strategies have been
      developed. Amongst them, molecular hybridization, which is based on the
      incorporation of two or more pharmacophores into a single molecule with a
      flexible linker, is one of the most practical approaches. This review aims to
      summarize the recent advances made towards the discovery of 4-quinolone hybrids
      as potential antibacterial agents as well as their structure-activity
      relationship (SAR). The enriched SAR may pave the way for the further rational
      development of 4-quinolone hybrids with excellent potency against both drug
      susceptible and drug-resistant bacteria.

PMID- 29031078
TI  - Structural design, synthesis and pharmacological evaluation of thiazoles against
      Trypanosoma cruzi.
AB  - Chagas disease is one of the most significant health problems in the American
      continent. benznidazole (BDZ) and nifurtimox (NFX) are the only drugs approved
      for treatment and exhibit strong side effects and ineffectiveness in the chronic
      stage, besides different susceptibility among T. cruzi DTUs (Discrete Typing
      Units). Therefore, new drugs to treat this disease are necessary. Thiazole
      compounds have been described as potent trypanocidal agents. Here we report the
      structural planning, synthesis and anti-T. cruzi evaluation of a new series of
      1,3-thiazoles (7-28), which were designed by placing this heterocycle instead of
      thiazolidin-4-one ring. The synthesis was conducted in an ultrasonic bath with 2
      propanol as solvent at room temperature. By varying substituents attached to the
      phenyl and thiazole rings, substituents were observed to retain, enhance or
      greatly increase their anti-T. cruzi activity. In some cases, methyl at position
      5 of the thiazole (compounds 9, 12 and 23) increased trypanocidal property. The
      exchange of phenyl for pyridinyl heterocycle resulted in increased activity,
      giving rise to the most potent compound against the trypomasigote form (14,
      IC50trypo = 0.37 MUM). Importantly, these new thiazoles were toxic for
      trypomastigotes without affecting macrophages and cardiomyoblast viability. The
      compounds were also evaluated against cruzain, and five of the most active
      compounds against trypomastigotes (7, 9, 12, 16 and 23) inhibited more than 70%
      of enzymatic activity at 10 MUM, among which compound 7 had an IC50 in the
      submicromolar range, suggesting a possible mechanism of action. In addition,
      examination of T. cruzi cell death showed that compound 14 induces apoptosis. We
      also examined the activity against intracellular parasites, revealing that
      compound 14 inhibited T. cruzi infection with potency similar to benznidazole.
      The antiparasitic effect of 14 and benznidazole in combination was also
      investigated against trypomastigotes and revealed that they have synergistic
      effects, showing a promising profile for drug combination. Finally, in mice
      acutely-infected with T. cruzi,14 treatment significanty reduced the blood
      parasitaemia and had a protective effect on mortality. In conclusion, we report
      the identification of compounds (7), (12), (15), (23) and (26) with similar
      trypanocidal activity of benznidazole; compounds (9) and (21) as trypanocidal
      agents equipotent with BDZ, and compound 14 with potency 28 times better than the
      reference drug without affecting macrophages and cardiomyoblast viability.
      Mechanistically, the compounds inhibit cruzain, and 14 induces T. cruzi cell
      death by an apoptotic process, being considered a good starting point for the
      development of new anti-Chagas drug candidates.

PMID- 29031079
TI  - A CMT2 family carrying the P7R mutation in the N- terminal region of the HSPB1
      gene.

PMID- 29031080
TI  - Endovascular therapy for vasospasm secondary to subarachnoid hemorrhage: A meta
      analysis and systematic review.
AB  - Endovascular therapy has been used as an alternative treatment for vasospasm
      following subarachnoid hemorrhage. The effectiveness and safety of endovascular
      therapy are still controversial. We performed a systematic review and meta
      analysis to identify any advantage of endovascular therapy over traditional
      medical treatment. We systematically reviewed related English publications by
      searching PubMed, Ovid, Cochrane library, and Web of Science up to May 2017.The
      risk ratios (RR) and 95% confidence intervals (CI) were synthesized with fixed
      effect model. Subgroup analyses and sensitivity analyses were conducted to check
      the robustness the result. Publication bias was measured with funnel plot. Eight
      cohort studies were included, receiving a mean score of 7 on the Newcastle-Ottawa
      Scale. The overall effect (RR 1.01, [95% CI 0.80-1.26]) found no significant
      difference in the outcome between the endovascular treatment and control groups
      but with heterogeneity (Chi2=18.07, p=0.01, I2=61%). Subgroup analyses stratified
      by country, year of publication, treatment modality, follow-up time, and
      sensitivity analysis by excluding the most biased study yielded the same result
      (RR 1.19, [95% CI 0.94-1.52]), with rare heterogeneity (Chi2=4.21, p=0.65, I2=0).
      Funnel plot was visually symmetric in sensitivity analysis. Despite good
      performance in reversing vasospasm in previous studies, endovascular therapy did
      not show superiority to traditional medical treatment in improving patient
      outcomes. Further randomized controlled studies are needed to elucidate this
      issue.

PMID- 29031081
TI  - Optimization of the Promega PowerSeqTM Auto/Y system for efficient integration
      within a forensic DNA laboratory.
AB  - The application of massively parallel sequencing (MPS) is growing in the forensic
      DNA field, as forensic DNA laboratories are continuously seeking methods to gain
      information from a limited or degraded forensic sample. However, the laborious
      nature of current MPS methodologies required for successful library preparation
      and sequencing leave opportunities for improvement to make MPS a practical option
      for processing forensic casework. In this study, the Promega PowerSeqTM Auto/Y
      System Prototype, a MPS laboratory workflow that incorporates multiplex
      amplification, was selected for optimization with the objectives to introduce
      automation for relieving manual processing, and to reduce the number of steps
      recommended by the standard protocol. Successful changes in the optimized
      workflow included a switch from column-based PCR purification to automatable bead
      based purification, adoption of the library preparation procedures by a liquid
      handling robot platform, and removal of various time-consuming quality checks.
      All data in this study were found to be concordant with capillary electrophoresis
      (CE) data and previously-generated MPS results from this workflow. Read abundance
      and allele balance, metrics related to sample interpretation reliability, were
      not significantly different when compared to samples processed with the
      manufacturer's protocol. All the modifications implemented resulted in increased
      laboratory efficiency, reduced the protocol steps associated with risk of
      contamination and human error events, and decreased manual processing time by
      approximately 12h. These findings provide forensic DNA laboratories a more
      streamlined option when considering implementation of a MPS workflow.

PMID- 29031082
TI  - Quantum associative memory with linear and non-linear algorithms for the
      diagnosis of some tropical diseases.
AB  - This paper presents the QAMDiagnos, a model of Quantum Associative Memory (QAM)
      that can be a helpful tool for medical staff without experience or laboratory
      facilities, for the diagnosis of four tropical diseases (malaria, typhoid fever,
      yellow fever and dengue) which have several similar signs and symptoms. The
      memory can distinguish a single infection from a polyinfection. Our model is a
      combination of the improved versions of the original linear quantum retrieving
      algorithm proposed by Ventura and the non-linear quantum search algorithm of
      Abrams and Lloyd. From the given simulation results, it appears that the
      efficiency of recognition is good when particular signs and symptoms of a disease
      are inserted given that the linear algorithm is the main algorithm. The non
      linear algorithm helps confirm or correct the diagnosis or give some advice to
      the medical staff for the treatment. So, our QAMDiagnos that has a friendly
      graphical user interface for desktop and smart-phone is a sensitive and a low
      cost diagnostic tool that enables rapid and accurate diagnosis of four tropical
      diseases.

PMID- 29031083
TI  - Neural network robust tracking control with adaptive critic framework for
      uncertain nonlinear systems.
AB  - In this paper, we aim to tackle the neural robust tracking control problem for a
      class of nonlinear systems using the adaptive critic technique. The main
      contribution is that a neural-network-based robust tracking control scheme is
      established for nonlinear systems involving matched uncertainties. The augmented
      system considering the tracking error and the reference trajectory is formulated
      and then addressed under adaptive critic optimal control formulation, where the
      initial stabilizing controller is not needed. The approximate control law is
      derived via solving the Hamilton-Jacobi-Bellman equation related to the nominal
      augmented system, followed by closed-loop stability analysis. The robust tracking
      control performance is guaranteed theoretically via Lyapunov approach and also
      verified through simulation illustration.

PMID- 29031084
TI  - Moving towards the benign: Automatic interpretation bias modification in
      dysphoria.
AB  - Automatic cognitive biases are important to theories of depression and reducing
      such biases may contribute to therapeutic gains. The present study examined (1)
      whether it was possible to reduce automatic interpretation biases (AIB) in a
      single session among dysphoric subjects and (2) whether the effects of modifying
      AIB generalized to other measures of cognition and emotion. 76 dysphoric students
      completed a modified semantic association paradigm in which they were randomized
      to receive active or random-feedback-based training. Groups did not differ on AIB
      at baseline. Compared to the placebo group, the active training group
      demonstrated decreased endorsement of negative AIB, faster endorsement of benign
      AIB, and slower rejection of benign AIB. AIB modification generalized to a
      separate measure of interpretation bias. Further, greater reductions in AIB
      predicted a more resilient emotional response pattern to a laboratory stressor.
      Implications of AIB modification for basic and clinical research are discussed.

PMID- 29031085
TI  - A study on the extrinsic sensitivity and counting efficiency of a gamma camera
      for a cylindrical source and a rectangular detector.
AB  - In this work, the extrinsic counting efficiency and extrinsic sensitivity of a
      cylindrical source and a gamma camera with a rectangular detector were determined
      using homogeneous Tc-99m. Scattered radiation effects were evaluated by both
      analyzing the energy spectrum of 99mTc for the scatter fraction and plotting the
      extrinsic counting efficiency and sensitivity. It is found that the scattered
      fraction values increased with increasing source thickness. Calculated extrinsic
      sensitivity shows a gradually decreasing trend with increasing source thickness.
      The extrinsic efficiency decreases with increasing source thickness. It is
      concluded that increasing source to detector distances results with increasing
      extrinsic counting efficiency but decreasing extrinsic sensitivity.

PMID- 29031086
TI  - Natural iron isotopes influence on the neutron transport.
AB  - As an iron is the main structural component of nuclear power plants as well as
      future fusion power plants, the validation of neutron incident data libraries of
      iron is a must. Presented paper fits into ongoing validation activities and
      presents measuring neutron leakage spectra in the 0.1-1.0MeV region from iron
      sphere of 100cm in diameter by hydrogen proportional detectors. The experimental
      result is compared with ENDF/B-VII.1, JEFF-3.2 and CIELO nuclear data libraries.
      No library reasonably well describes whole region under study. Furthermore,
      elastic and inelastic XS sensitivity analysis for all iron isotopes was carried
      out. 54Fe isotope elastic XS influence is comparable with 56Fe XS influence up to
      0.8MeV. 57Fe isotope elastic XS is significant in the region of 0.14-0.15MeV.
      Additionally, there are large differences among libraries in both elastic and
      inelastic XS for 57Fe. Furthermore, it was found that 58Fe isotope XS has
      negligible influence on the results. As a neutron source, 252Cf with initial
      emission rate of 9.53E8 n/s was used in this experiment.

PMID- 29031087
TI  - Characterization of the radiosynthesis and purification of [18F]THK-5351, a PET
      ligand for neurofibrillary tau.
AB  - This work characterizes the radiochemical synthesis, purification, and
      formulation of [18F]THK-5351, a tau PET radioligand, and develops an automated
      radiosynthesis routine (ELIXYS, Sofie Biosciences). Nucleophilic
      radiofluorination reaction was complete by 7min at 110 degrees C with
      radiochemical yields proportional to precursor mass (0.1-0.5mg). Optimized HPLC
      purification produced radiotracer product with no chemical impurities observed on
      analytical HPLC in formulation. Automated radiosynthesis (ELIXYS), HPLC
      purification and formulation was completed in 86min producing formulated product
      suitable for human research use.

PMID- 29031090
TI  - Recreational drug use and risk of HIV infection among men who have sex with men:
      A cross-sectional study in Shenzhen, China.
AB  - BACKGROUND: Recreational drug use has increased in recent years, especially among
      MSM, and has been found to be associated with higher risk of HIV infection.
      However, there is limited information about current recreational drug use among
      MSM in Shenzhen which is an international gateway city to China with a rapidly
      expanding MSM population. METHODS: A cross-sectional survey among MSM in Shenzhen
      was conducted and was used to collected information on demographics, sexual
      behavior and drug use via questionnaires. Serologic results on HIV and syphilis
      were obtained from laboratory assays. We performed logistic regression analysis
      to evaluate correlates with drug use. RESULTS: Among the 1935 MSM surveyed, 12.7%
      reported use of recreational drugs in the past six months. Rush poppers had
      become the most frequently used drug (10.6%). Risk factors associated with the
      use of recreational drugs included being unmarried, non-Han ethnicity, having
      high education level, seeking male sex partners via the internet, having multiple
      male sex partners, performing receptive role during anal sex, and having
      unprotected anal intercourse. Recreational drug use was significantly associated
      with higher risk of both HIV and syphilis infections (aOR:1.89, 95% CI:1.28-2.79;
      aOR:1.79, 95% CI:1.25-2.60, respectively). CONCLUSIONS: Recreational drug use is
      associated with increased risk of HIV and syphilis infections among MSM in
      Shenzhen. Rush poppers were the most popular recreational drug. This finding
      suggests the need for targeted prevention and behavioral intervention programs to
      control the recreational drug use, and to reduce HIV and other sexually
      transmitted diseases among MSM in Shenzhen and internationally.

PMID- 29031088
TI  - Probing the correlation of neuronal loss, neurofibrillary tangles, and cell death
      markers across the Alzheimer's disease Braak stages: a quantitative study in
      humans.
AB  - Clarifying the mechanisms connecting neurofibrillary tangle (NFT) neurotoxicity
      to neuronal dysfunction in humans is likely to be pivotal for developing
      effective treatments for Alzheimer's disease (AD). To model the temporal
      progression of AD in humans, we used a collection of brains with controls and
      individuals from each Braak stage to quantitatively investigate the correlation
      between intraneuronal caspase activation or macroautophagy markers, NFT burden,
      and neuronal loss, in the dorsal raphe nucleus and locus coeruleus, the earliest
      vulnerable areas to NFT accumulation. We fit linear regressions with each count
      as outcomes, with Braak score and age as the predictors. In progressive Braak
      stages, intraneuronal active caspase-6 positivity increases both alone and
      overlapping with NFTs. Likewise, the proportion of NFT-bearing neurons showing
      autophagosomes increases. Overall, caspases may be involved in upstream cascades
      in AD and are associated with higher NFTs. Macroautophagy changes correlate with
      increasing NFT burden from early AD stages.

PMID- 29031089
TI  - 17beta-estradiol regulates the RNA-binding protein Nova1, which then regulates
      the alternative splicing of estrogen receptor beta in the aging female rat brain.
AB  - Alternative RNA splicing results in the translation of diverse protein products
      arising from a common nucleotide sequence. These alternative protein products are
      often functional and can have widely divergent actions from the canonical
      protein. Studies in humans and other vertebrate animals have demonstrated that
      alternative splicing events increase with advanced age, sometimes resulting in
      pathological consequences. Menopause represents a critical transition for women,
      where the beneficial effects of estrogens are no longer evident; therefore,
      factors underlying increased pathological conditions in women are confounded by
      the dual factors of aging and declining estrogens. Estrogen receptors (ERs) are
      subject to alternative splicing, the spliced variants increase following
      menopause, and they fail to efficiently activate estrogen-dependent signaling
      pathways. However, the factors that regulate the alternative splicing of ERs
      remain unknown. We demonstrate novel evidence supporting a potential biological
      feedback loop where 17beta-estradiol regulates the RNA-binding protein Nova1,
      which, in turn, regulates the alternative splicing of ERbeta. These data increase
      our understanding of ER alternative splicing and could have potential
      implications for women taking hormone replacement therapy after menopause.

PMID- 29031091
TI  - Hexavalent chromium removal by multilayer membrane assisted by photocatalytic
      couple nanoparticle from both permeate and retentate.
AB  - In this study, a novel photocatalytic thin film nanocomposite (TFC) membrane was
      prepared for removal of hexavalent chromium (Cr(VI)) from aqueous solution. In
      this regards, a TFC membrane was modified by a layer of chitosan as an adsorbent
      and then was coated with a layer of synthesized photocatalytic nanoscale
      zerovalent iron@titanium dioxide (nZVI@TiO2) nanoparticles via layer-by-layer
      (LBL) technology. Prepared membranes were characterized by X-ray diffraction
      (XRD), energy dispersive X-ray spectroscopy (EDX), field emission scanning
      electron microscopy (FESEM), atomic force microscopy (AFM) and contact angle
      analysis. The Cr(VI) removal efficiency of the membranes was evaluated by batch
      removal and dynamic filtration tests. The water flux was increased from 26.2 to
      39.7l/m2h as a consequence of improved hydrophilicity which was approved by
      contact angle analysis. The modified TFC membrane has shown the significant
      removal of Cr(VI) in retentate as well as the permeate stream. Further, the
      Cr(VI) removal of retentate flow decreased with increasing pH and feed
      concentration whereas the Cr(VI) removal of permeate was enhanced with increasing
      initial feed concentration. Increasing the flux recovery from 62% (for neat TFC)
      to 87% (for modified TFC membrane) demonstrated that the modification of membrane
      improved the anti-fouling property of the modified membrane.

PMID- 29031092
TI  - One-step synthesis of silicon carbide foams supported hierarchical porous sludge
      derived activated carbon as efficient odor gas adsorbent.
AB  - Hierarchical porous sludge-derived activated carbon coated on macroporous silicon
      carbide (SiC) foams substrate has been facilely fabricated via a simple one-step
      strategy by utilizing sludge as carbon source, and jointly using zinc chloride
      and hexadecanol as pore forming agents. The sludge-derived carbon has been
      confirmed to be hierarchical macro-meso-microporous structure based on detailed
      characterization by scanning electron microscopy (SEM), X-ray diffraction (XRD),
      Raman spectra and nitrogen adsorption-desorption measurement. The adsorption
      tests showed that the hierarchical porous sludge-derived activated carbon
      fabricated by one-step pore-forming (zinc chloride and hexadecanol microemulsion
      mixture) possesses excellent adsorption capacity (259.9mgg-1, breakthrough time
      reach 90min and saturation end-time up to 140min) of methyl mercaptan (CH3SH).
      The excellent adsorption performance can be attributed to the macroporous SiC
      foam skeleton and the mesopores channel formed by nonionic surfactant hexadecanol
      micelles, as well as the micropores activated by ZnCl2 as odor capture sites. The
      proposed pore-forming strategy paves an avenue for the sludge disposal and even
      the development of bio-derived materials.

PMID- 29031093
TI  - Three-dimensional Ag2O/Bi5O7I p-n heterojunction photocatalyst harnessing UV-vis
      NIR broad spectrum for photodegradation of organic pollutants.
AB  - Ag2O nanoparticles-loaded Bi5O7I microspheres forming a three dimensional
      Ag2O/Bi5O7I p-n heterojunction photocatalyst with wide-spectrum response were
      synthesized in this study. The results of transmission electron microscopy
      observations revealed that the Ag2O nanoparticles with the diameter of ca. 10
      20nm were distributed on the surfaces of Bi5O7I nanosheets. The as-synthesized
      Ag2O/Bi5O7I exhibited an excellent wide-spectrum response to wavelengths ranging
      from ultraviolet (UV) to near-infrared (NIR), indicating its potential for
      effective utilization of solar energy. Compared with pure Bi5O7I, the Ag2O/Bi5O7I
      composite also demonstrated excellent photocatalytic activity for the degradation
      of Bisphenol A and phenol in aqueous solution under visible LED light
      irradiation. Among samples, the 20% Ag2O/Bi5O7I composite photocatalyst showed
      the highest photocatalytic activity for the degradation of Bisphenol A and phenol
      in aqueous solution. In addition, the 20% Ag2O/Bi5O7I composite also exhibited a
      photocatalytic activity for the degradation of Bisphenol A under NIR light
      irradiation. The improved photocatalytic activity is attributed to the formation
      of a p-n heterojunction between Ag2O and Bi5O7I, allowing the efficient
      utilization of solar energy (from UV to NIR) and high separation efficiency of
      photogenerated electron-hole pairs. The present work is desirable to explore a
      possible avenue for the full utilization of solar energy.

PMID- 29031094
TI  - Risk assessment of dietary lead exposure among First Nations people living on
      reserve in Ontario, Canada using a total diet study and a probabilistic approach.
AB  - Indigenous peoples have elevated risk of lead (Pb) exposure as hunted traditional
      food can be contaminated with lead-containing ammunition. Recent scientific
      consensus states that there is no threshold level for Pb exposure. The objective
      of this study was to estimate dietary exposure to Pb among First Nations living
      on-reserve in the province of Ontario, Canada. A total diet study was constructed
      based on a 24-h recall and Pb concentrations for traditional foods from the First
      Nations Food, Nutrition, and Environment Study (FNFNES) and Pb concentrations in
      market foods from Health Canada. A probabilistic assessment of annual and
      seasonal traditional food consumption was conducted. Results indicate that
      traditional foods, particularly moose and deer meat. are the primary source of
      dietary Pb intake (73%), despite providing only 1.8% of the average caloric
      intake. The average dietary Pb exposure (0.21MUg/kg/d) in the First Nations
      population in Ontario was 1.7 times higher than the dietary Pb exposure in the
      general Canadian population. Pb intake was associated with an estimated average
      increase in systolic blood pressure of 1.2mmHg. These results indicate that
      consumption of foods hunted with Pb containing ammunition and shot puts the
      population at elevated risk of Pb toxicity.

PMID- 29031095
TI  - Sustainable superior function of the synthesized NixCo1-xFe2Oz nanosphere on the
      destruction of chlorinated biphenyls in the effluent.
AB  - NixCo1-xFe2Oz composite oxide nanosphere was successfully prepared, to degrade 2
      monochlorobiphenly (CB-1) in continuous-flow fixed-bed microreactor at GHSV of
      20000h-1. The five cycles of temperature-dependent run experiments between 150
      and 350 degrees C showed its superior activity with a CB-1 conversion of more
      than 95% above 300 degrees C over Ni0.5Co0.5Fe2Oz. Importantly, the sustainable
      higher reactivity could be observed over prolonged 600min reaction times after
      the 5th run test. The degradation products detected as biphenyl and
      monochlorobenzene with yield ratio of 129, account for 0.24% and 0.0011% of
      initial CB-1 respectively. This indicated the weak occurrence of
      hydrodechlorination and breakage of CC bridge bond during the degradation of CB
      1. The possibly dominant occurrence of oxidative degradation probably follows
      Mars-van Krevelen mechanism, resulting in the generation of the formic, acetic,
      propanoic and butyric acids and so on. Due to the high oxygen mobility over
      Ni0.5Co0.5Fe2Oz nanosphere, the consumed oxygen species could be compensated
      rapidly by the gas phase oxygen via O2->O2- -> 2O- -> 2O2-. The interaction among
      different elements in Ni0.5Co0.5Fe2Oz nanosphere confirmed by the derivation of
      the electron cloud, enhanced the mobility of the reactive oxygen species, which
      would be beneficial for the oxidation of chlorinated biphenyls.

PMID- 29031096
TI  - Removal of metallic Al and Al/Zn alloys in MSWI bottom ash by alkaline treatment.
AB  - In order to reduce the leaching of pollutants and remove the Al and Zn/Al alloy
      from municipal solid waste incineration bottom ash (MSWIBA), an optimized
      alkaline pre-treatment procedure was developed in this study. The influences of
      alkaline conditions on the removal rate of Al and Zn/Al alloy were investigated,
      including [OH]- concentration, temperature, particle size, liquid/solid ratio and
      treatment duration. The experimental results showed that the optimized alkaline
      pre-treatment conditions to efficiently remove the Al and Zn/Al alloy was by
      using a minimum of 1.0mol/l [OH]-, at 55 degrees C and with a minimal
      liquid/solid ratio of 5. The removal rate of Al and Zn/Al alloy followed an S
      shape curve, in which the slow beginning stage was attributed to the protection
      of the oxidation layer and the quenched product around the Al and Al/Zn alloy.
      After 3h of the optimized alkaline pre-treatment, the leaching of Cr, Cu, Pb and
      Zn of the treated MSWIBA was reduced by more than 90% of that of the original
      MSWIBA. The alkali-silica reaction test further indicated that the expansion of
      concrete prepared with the pre-treated MSWIBA was significantly reduced and there
      was no macro-crack or spalling damage on the surface of the tested specimens.

PMID- 29031097
TI  - The tall and the short of it: An investigation of height ideals, height
      preferences, height dissatisfaction, heightism, and height-related quality of
      life impairment among sexual minority men.
AB  - Human height has attracted empirical interest from a variety of psychological
      perspectives. However, little research has explored height from the perspective
      of sexual minority men, inclusive of their height beliefs, height preferences,
      height dissatisfaction, experiences of heightism, and height-related quality of
      life impairment. We explored these height variables in 2733 sexual minority men
      who completed a survey distributed nationwide to Australian and New Zealander
      users of geosocial-networking smartphone applications. Results showed that men's
      ideal height (M=182.26cm, SD=5.93cm) was taller than their actual height
      (M=178.96cm, SD=7.52cm). Shorter and taller men reported negative and positive
      treatment from others due to their height, respectively, with the cross-over
      (i.e., neutral) point at approximately 175-176cm. Heightism was reported by 11.0%
      of men. Height dissatisfaction and heightism were uniquely associated with
      quality of life impairment; the size of these associations was small.

PMID- 29031098
TI  - Stepwise construction of a metabolic network in Event-B: The heat shock response.
AB  - There is a high interest in constructing large, detailed computational models for
      biological processes. This is often done by putting together existing submodels
      and adding to them extra details/knowledge. The result of such approaches is
      usually a model that can only answer questions on a very specific level of
      detail, and thus, ultimately, is of limited use. We focus instead on an approach
      to systematically add details to a model, with formal verification of its
      consistency at each step. In this way, one obtains a set of reusable models, at
      different levels of abstraction, to be used for different purposes depending on
      the question to address. We demonstrate this approach using Event-B, a
      computational framework introduced to develop formal specifications of
      distributed software systems. We first describe how to model generic metabolic
      networks in Event-B. Then, we apply this method for modeling the biological heat
      shock response in eukaryotic cells, using Event-B refinement techniques. The
      advantage of using Event-B consists in having refinement as an intrinsic feature;
      this provides as a final result not only a correct model, but a chain of models
      automatically linked by refinement, each of which is provably correct and
      reusable. This is a proof-of-concept that refinement in Event-B is suitable for
      biomodeling, serving for mastering biological complexity.

PMID- 29031099
TI  - Shear wave elastography for characterization of breast lesions: Shearlet
      transform and local binary pattern histogram techniques.
AB  - Shear wave elastography (SWE) examination using ultrasound elastography (USE) is
      a popular imaging procedure for obtaining elasticity information of breast
      lesions. Elasticity parameters obtained through SWE can be used as biomarkers
      that can distinguish malignant breast lesions from benign ones. Furthermore, the
      elasticity parameters extracted from SWE can speed up the diagnosis and possibly
      reduce human errors. In this paper, Shearlet transform and local binary pattern
      histograms (LBPH) are proposed as an original algorithm to differentiate
      malignant and benign breast lesions. First, Shearlet transform is applied on the
      SWE images to acquire low frequency, horizontal and vertical cone coefficients.
      Next, LBPH features are extracted from the Shearlet transform coefficients and
      subjected to dimensionality reduction using locality sensitivity discriminating
      analysis (LSDA). The reduced LSDA components are ranked and then fed to several
      classifiers for the automated classification of breast lesions. A probabilistic
      neural network classifier trained only with seven top ranked features performed
      best, and achieved 98.08% accuracy, 98.63% sensitivity, and 97.59% specificity in
      distinguishing malignant from benign breast lesions. The high sensitivity and
      specificity of our system indicates that it can be employed as a primary
      screening tool for faster diagnosis of breast malignancies, thereby possibly
      reducing the mortality rate due to breast cancer.

PMID- 29031100
TI  - Discovery of a new mechanism for regulation of plant triacylglycerol metabolism:
      The peanut diacylglycerol acyltransferase-1 gene family transcriptome is highly
      enriched in alternative splicing variants.
AB  - Triacylglycerols (TAGs) are the most important energy storage form in oilseed
      crops. Diacylglycerol acyltransferase (DGAT) catalyzes the rate-limiting step of
      the Kennedy pathway of TAG biosynthesis. To date, little is known about the
      regulation of DGAT activity in peanut (Arachis hypogaea), an agronomically
      important oilseed crop that is cultivated in many parts of the world. In this
      study, seven distinct forms of type 1 DGAT (AhDGAT1.1-AhDGAT1.7) were identified,
      cloned, and characterized. Comparisons of the nucleotide sequences and gene
      structures revealed many different splicing variants of AhDGAT1, some of which
      displayed different organ-specific expression patterns. A representative gene
      (AhDGAT1.1) was transformed into wild-type tobacco and was shown to increase seed
      fatty acid (FA) content by 14.7%-20.9%. All seven AhDGAT1s were expressed in TAG
      deficient Saccharomyces cerevisiae strain H1246; the five longest AhDGAT1
      variants generated high levels of acyltransferase activity and complemented the
      free fatty acid lethality phenotype in this strain. The alternative splicing that
      gives rise to AhDGAT1.2 and AhDGAT1.4 creates predicted protein C-terminal
      truncations. The proteins encoded by these two variants were not active and did
      not complement the fatty acid sensitivity in H1246. These results were verified
      by visualization of intracellular lipid droplets using Nile Red staining.
      Collectively, the results presented here represent the first comprehensive
      analysis of the peanut DGAT1 gene family, which, unlike in other published plant
      DGAT1 sequences, shows widespread alternative splicing that may affect the
      expression patterns and enzyme activities of some members of the gene family.

PMID- 29031101
TI  - Radionuclides in mushrooms and soil-to-mushroom transfer factors in certain areas
      of China.
AB  - Activity concentrations of 238U, 226Ra, 228Ra, 137Cs and 40K in 64 mushroom
      samples collected in China from Yunnan, Fujian and Heilongjiang Provinces, were
      measured. Gamma-ray emissions were determined by using high-purity germanium
      (HPGe) gamma spectrometry. The range of concentrations (Bq kg-1 dry weight) for
      238U, 226Ra, 228Ra, 137Cs and 40K in all investigated mushroom samples were from
      0.12 to 12, 0.05 to 7.5, 0.14 to 14, MDC(<0.01) to 339, and 396 to 1880,
      respectively. Activity concentrations of 137Cs in mushrooms showed some variation
      between species sampled at the same site. To calculate soil to mushroom transfer
      factors, levels of radionuclide in 15 paired soil samples and mushrooms were also
      investigated. The median transfer factors for 238U, 226Ra, 228Ra, 137Cs and 40K
      were 8.32 * 10-2, 3.03 * 10-2, 6.69 * 10-2, 0.40 and 1.19, respectively. The
      results were compared with values of other areas.

PMID- 29031102
TI  - Identifying the loss of functional independence of older people residing in the
      community: Validation of the PRISMA-7 instrument in Brazil.
AB  - The identification of the older people who are functionally dependant is
      essential for planning interventions with emphasis on secondary and tertiary
      prevention. Therefore, a simplified tool, able to identify these individuals for
      a more comprehensive evaluation, is required. However, the use of a measuring
      tool in a different socio-cultural context requires prior adaptation. This
      article aims to verify the psychometric properties of the PRISMA-7 in Brazilian
      context. This instrument was previously shown as able to identify older persons
      living in the community who have risk of functional loss in a Canadian study. In
      a sample of 1748 older persons, the internal consistency assessed by Cronbach's
      alpha showed a borderline value credited to the reduced number of questionnaire
      items. Factor analysis identified two well correlated factors, except for items 2
      and 6. For criterion validity the SMAF scale (French acronym, Functional Autonomy
      Measurement System) was used as the gold standard. The analysis of the ROC curve
      indicated a sensitivity of 74.4% and specificity of 87.4% for the cut-off point
      of 4, while the Canadian version had a cut-off point of 3 for disability
      detection. Inter and intra-observer reliability, investigated by the Kappa Cohen
      were high and statistically significant. In conclusion, the results suggest that
      the validation process was adequate, and recommend the Brazilian version of
      PRISMA-7, to track older people with functional loss in the community.

PMID- 29031103
TI  - Kaposi's sarcoma herpesvirus-induced endothelial cell reprogramming supports
      viral persistence and contributes to Kaposi's sarcoma tumorigenesis.
AB  - Kaposi's sarcoma (KS) is an endothelial tumor causally linked to Kaposi's sarcoma
      herpesvirus (KSHV) infection. At early stages of KS, inflammation and aberrant
      neoangiogenesis are predominant, while at late stages the disease is
      characterized by the proliferation of KSHV-infected spindle cells (SC). Since
      KSHV infection modifies the endothelial cell (EC) identity, the origin of SCs
      remains elusive. Yet, pieces of evidence indicate the lymphatic origin. KSHV
      infected ECs display increased proliferative, angiogenic and migratory capacities
      which account for KS oncogenesis. Here we propose a model in which KSHV
      reprograms the EC identity, induces DNA damage and establishes a dysregulated
      gene expression program involving interplay of latent and lytic genes allowing
      continuous reinfection of ECs attracted to the tumor by the secretion of virus
      induced cellular factors.

PMID- 29031104
TI  - Evaluation of the Gauss-Eyring model to predict thermal inactivation of micro
      organisms at short holding times.
AB  - Application of mild (non)-thermal processing technologies have received
      considerable interest as alternative to thermal pasteurisation, because of its
      shorter holding time and lower temperature aiming for an improved product
      quality. To understand and develop these alternative technologies, like pulsed
      electric fields, a proper comparison between the conventional thermal and
      alternative process is necessary. Up to recent, no suitable models were available
      to predict the inactivation of micro-organisms by a thermal process at a chosen
      short holding time, due to non-linearity. The recently developed Gauss-Eyring
      model with two variables temperature and time has the properties to be a suitable
      model to apply for short holding times, and was tested for this purpose.
      Therefore, this study aims to validate if the Gauss-Eyring model can be used to
      describe non-linear isothermal (a fixed temperature with varying holding time)
      and isotime (a fixed holding time with varying temperature) thermal inactivation
      data, and if it is a suitable model to predict the thermal inactivation as a
      function of temperature for short holding times. Inactivation data of Escherichia
      coli, Listeria monocytogenes, Lactobacillus plantarum, Salmonella Senftenberg and
      Saccharomyces cerevisiae in orange juice were collected via isothermal and
      isotime inactivation kinetics. Survival of the tested micro-organisms was
      modelled with the Gauss-Eyring model, which contains three parameters sigma, Tr
      and Z. The transition of 'no inactivation' to 'inactivation' (i.e. the 'shoulder'
      in inactivation curves) can be characterised as the temperature-time (T,t)
      combination where T=Tr-Z.log10(t), with Tr as the reference temperature defined
      for 1s treatment, Z as the temperature needed for a 10-fold increase of decrease
      of the holding time t, and sigma as the temperature width of the distribution.
      The Gauss-Eyring model fitted well to the experimental data, and revealed
      different sensitivity for the tested micro-organisms. Based on the parameter
      estimations, survival curves for the desired short holding times were predicted.

PMID- 29031105
TI  - Effects of processing parameters on the inactivation of Bacillus cereus spores on
      red pepper (Capsicum annum L.) flakes by microwave-combined cold plasma
      treatment.
AB  - The efficacy of microwave-combined cold plasma treatment (MCPT) for inactivating
      Bacillus cereus spores contaminating red pepper (Capsicum annum L.) flakes was
      investigated. The effects of red pepper drying method, particle size, and water
      activity (aw) were also evaluated at two levels of microwave power (1700 and
      2500W/cm2). The inactivation effect of MCPT was higher at higher microwave power.
      Spore reduction was more effective with vacuum-dried red pepper than far-infrared
      dried flakes. A significantly higher level of spore reduction was observed with
      the red pepper sample with a smaller surface to volume ratio when one surface
      (exterior surface) was inoculated (p<0.05). Spore reduction by MCPT at high
      microwave power increased from 1.7 to 2.6logspores/cm2 when the aw of flake
      increased from 0.4 to 0.9 (p<0.05). MCPT did not change the color of red pepper
      flakes. MCPT demonstrated potential as a microbial decontaminating technology for
      red pepper flakes.

PMID- 29031106
TI  - New insights into resistance to colistin and third-generation cephalosporins of
      Escherichia coli in poultry, Portugal: Novel blaCTX-M-166 and blaESAC genes.
AB  - The increasing incidence of intestinal colonization with extended-spectrum beta
      lactamase (ESBL)-producing Enterobacteriaceae and Gram negative organisms that
      has been observed in food animals such as poultry, cattle and pigs, are
      suggestive that animals, food and environment are potential sources of ESBL
      producing bacteria. Hence, the aim of this study was to characterized commensal
      E. coli obtained from healthy broiler and turkey flocks at slaughter for the
      presence of penicillinases-, ESBL-, extended-spectrum AmpC (ESAC)-, plasmid
      mediated quinolone resistance- and MCR-encoding genes. Study of clonal
      relatedness showed genetic diversity among CTX-M-type, SHV-12 and TEM-52
      producing isolates with human isolates of the same type, was also assessed. We
      detected that eleven (5.4%, 11/202) and forty-five (2.2%, 45/185) E. coli
      isolates from broilers and turkeys, respectively, carried blaESBL or blaESAC
      genes and two isolates from turkeys carried mcr-1 gene. A new variant blaCTX-M
      166 was reported in a multidrug resistant isolate from a broiler flock. Overall,
      we detected a diversity of resistance mechanisms among E. coli from food
      producing animals, all of them with high importance at a public health level.

PMID- 29031107
TI  - Accuracy, precision and inter-rater reliability of micro-CT analysis of false
      starts on bones. A preliminary validation study.
AB  - Micro computed tomography (micro-CT) has already been proposed as a useful
      technique for the qualitative analysis of false starts (FS) produced on human
      bones, although the reliability and the error rate of this technique have not
      been tested yet, neither for qualitative nor for quantitative assessments. The
      aim of the present study was to test the morphological agreement, accuracy,
      precision and inter-rater reliability of micro-CT analysis of FS on bones. The
      morphological agreement was assessed through the degree of concordance among the
      3 independent blind raters in the identification of the shape of 24 FS manually
      produced on bones by 3 different saws (8 FS for each saw). The accuracy was
      calculated through the percentage of error in the automatic and manual
      measurement of the diameter of a reference object. The precision was calculated
      as CV% of multiple measurements performed by 3 independent blind raters on the
      reference object and one bone sample acquired 20 times. The inter-rater
      reliability was assessed as intraclass correlation coefficient (ICC) among
      measurements performed by 3 independent blind raters, assessing 24 FS produced
      using 3 different saws. The results demonstrated that both qualitative and
      quantitative analysis were reproducible and robust. Micro-CT analysis showed a
      100% morphological agreement, a high level of accuracy (percentage error < 0,5%),
      precision (CV% < 5%) and inter-rater reliability (ICC > 0.995), when FS were
      analyzed by forensic pathologists and/or radiologists with adequate expertise.
      Obviously, further validation studies are needed, including a higher number of
      samples produced by a wider variety of saws and multiple operators.

PMID- 29031108
TI  - Accessibility of fast food outlets is associated with fast food intake. A study
      in the Capital Region of Denmark.
AB  - Literature suggests that people living in areas with a wealth of unhealthy fast
      food options may show higher levels of fast food intake. Multilevel logistic
      regression analyses were applied to examine the association between GIS-located
      fast food outlets (FFOs) and self-reported fast food intake among adults (+ 16
      years) in the Capital Region of Denmark (N = 48,305). Accessibility of FFOs was
      measured both as proximity (distance to nearest FFO) and density (number of FFOs
      within a 1km network buffer around home). Odds of fast food intake >= 1/week
      increased significantly with increasing FFO density and decreased significantly
      with increasing distance to the nearest FFO for distances <= 4km. For long
      distances (>4km), odds increased with increasing distance, although this applied
      only for car owners. Results suggest that Danish health promotion strategies need
      to consider the contribution of the built environment to unhealthy eating.

PMID- 29031109
TI  - Application of novel ternary deep eutectic solvents as a functional monomer in
      molecularly imprinted polymers for purification of levofloxacin.
AB  - A series of ecofriendly ternary deep eutectic solvents (DESs) with different
      molar ratios were prepared as candidate functional monomers. Three of the optimal
      ternary DESs as functional monomers were applied to the preparation of
      molecularly imprinted polymers (MIPs). After synthesis, the proposed polymers
      were characterized by elemental analysis (EA), scanning electron microscopy
      (SEM), thermogravimetric analysis (TGA), Brunauer-Emmett-Teller surface area
      measurements (BET) and Fourier transform infrared spectroscopy (FT-IR). These
      MIPs based on ternary DESs with different molar ratios exhibited different
      absorption capacities of levofloxacin. A sample of levofloxacin (500ng) was
      dissolved in a millet extractive (10mL). All MIPs were used as SPE adsorbents to
      purify the extracts. According to characterization result, the ternary DES-3
      (1:3:1.5) was joined in the synthetic process of MIP-1. The green ternary DES-3
      based MIPs had the best selectivity recovery for levofloxacin (91.4%) from the
      millet extractive. The best selectivity of MIP-1 was attributed to the novel
      monomer (ternary DES) in the preparation of the materials. Overall, ternary DES
      based MIPs have potential applications as media in many research areas.

PMID- 29031110
TI  - Determination of l-glutamic acid and gamma-aminobutyric acid in mouse brain
      tissue utilizing GC-MS/MS.
AB  - A rapid and selective method for the quantitation of neurotransmitters, l
      Glutamic acid (GA) and gamma-Aminobutyric acid (GABA), was developed and
      validated using gas chromatography-tandem mass spectrometry (GC-MS/MS). The novel
      method utilized a rapid online hot GC inlet gas phase sample derivatization and
      fast GC low thermal mass technology. The method calibration was linear from 0.5
      to 100MUg/mL, with limits of detections of 100ng/mL and 250ng/mL for GA and GABA,
      respectively. The method was used to investigate the effects of deletion of
      organic anion transporter 1 (Oat1) or Oat3 on murine CNS levels of GA and GABA at
      3 and 18 mo of age, as compared to age matched wild-type (WT) animals. Whole
      brain concentrations of GA were comparable between WT, Oat1-/-, and Oat3-/- 18 mo
      at both 3 and 18 mo of age. Similarly, whole brain concentrations of GABA were
      not significantly altered in either knockout mouse strain at 3 or 18 mo of age,
      as compared to WT. These results indicate that the developed GC-MS/MS method
      provides sufficient sensitivity and selectivity for the quantitation of these
      neurotransmitters in mouse brain tissue. Furthermore, these results suggest that
      loss of Oat1 or Oat3 function in isolation does not result in significant
      alterations in brain tissue levels of GA or GABA.

PMID- 29031111
TI  - Immobilization of sugars in supermacroporous cryogels for the purification of
      lectins by affinity chromatography.
AB  - Lectins are glycoproteins that bind to carbohydrates or glycoconjugates by
      specific interactions. The specificity of lectins to various carbohydrates is a
      determinant factor in the choice of ligand for the chromatographic matrix when
      using chromatography as a lectin purification technique. In this work, the
      immobilization of three different aminated carbohydrates on the surface of
      macroporous polymeric cryogels was evaluated. Carbohydrates were immobilized on
      cryogel surfaces via the glutaraldehyde method to create spacer arms, reducing
      steric hindrance. The immobilized N-acetyl-d-glucosamine and N-acetyl-d
      mannosamine concentrations contained approximately 130mg of carbohydrate/g
      dehydrated cryogel, while the N-acetyl-d-galactosamine contained 105mg of
      carbohydrate/g dehydrated cryogel. Scanning electron microscopy showed that the
      physical structure and porosity of the chromatographic columns were not affected
      by the immobilization process, maintaining an elevated hydration capacity and the
      macroporous structure of the cryogels. Adsorption of concanavalin A on cryogels
      functionalized with N-acetyl-d-glucosamine (cryo-d-GlcNAc) was tested, as well as
      its reuse capability. After 5 cycles of use, cryo-d-GlcNAc was shown to be
      stable, with an adsorptive capacity of around 50mg/g. Carbohydrate immobilization
      in polyacrylamide cryogels was satisfactory, with promise for applications in
      lectin purification processes.

PMID- 29031112
TI  - Quantitative analysis of antithrombin III binding site in low molecular weight
      heparins by exhausetive heparinases digestion and capillary electrophoresis.
AB  - The antithrombin III (ATIII)-binding site, which contains a special 3-O-sulfated,
      N-sulfated glucosamine residue with or without 6-O-sulfation, is mainly
      responsible for the anticoagulant activity of heparin. Undergoing the chemical
      depolymerization process, the preservation of the ATIII-binding site in low
      molecular weight heparins (LMWHs) are varied leading to the fluctuation of the
      anticoagulant activity. Herein we report a capillary electrophoresis (CE) method
      in combination with heparinase digestion and affinity chromatography for the
      measurement of molar percentage of ATIII-binding site of LMWHs. After
      exhaustively digesting LMWHs with the mixture of heparinase I, II and III, almost
      all the resulting oligosaccharide building blocks, including the three 3-O
      sulfated tetrasaccharides derived from the ATIII-binding site, were resolved by
      CE separation. The peak area of each building block permits quantification of the
      molar percentage of the ATIII-binding site. The peaks corresponding to the 3-O
      sulfated tetrasaccharides were assigned based on the linear relationship between
      the electrophoretic mobilities of the oligosaccharides and their charge to mass
      ratios. The peak assignment was further confirmed by analysis of the high ATIII
      affinity fractions, which contains much high 3-O-sulfated tetrasaccharides. With
      the method, the molar percentage of the ATIII-binding site of enoxaparin from
      different batches and different manufactures were measured and compared. It was
      demonstrated that the CE method provides more precise data for assessing the anti
      FXa activity than that of the biochemical assay method.

PMID- 29031114
TI  - Neo-clerodane diterpenoids from the whole plants of Scutellaria formosana.
AB  - Scuteformoids A-J, ten previously undescribed neo-clerodane diterpenoids along
      with one known analogue, were isolated from petroleum ether soluable fraction of
      the whole plants of Scutellaria formosana. The differences among these compounds
      are the substituents and stereochemistry at C-13. Their structures were
      elucidated by 1D and 2D NMR experiments, and the absolute configurations of
      Scuteformoids A, C, E, F, and I were further confirmed by single-crystal X-ray
      diffraction. Scuteformoids A, C, D, F, H, and I were evaluated for their
      inhibitory effects against HIV lytic replication and cytotoxic activities. All of
      them showed weak anti-HIV activities, with EC50 values ranging from 48.24 to
      79.17 MUg/mL.

PMID- 29031113
TI  - Cross-sectional and longitudinal small animal PET shows pre and post-synaptic
      striatal dopaminergic deficits in an animal model of HIV.
AB  - INTRODUCTION: In vivo imaging biomarkers of various HIV neuropathologies,
      including dopaminergic dysfunction, are still lacking. Towards developing
      dopaminergic biomarkers of brain involvement in HIV, we assessed the pre and
      postsynaptic components of the dopaminergic system in the HIV-1 transgenic rat
      (Tg), a well-characterized model of treated HIV+ patients, using small-animal PET
      imaging. METHODS: Fifteen to 18 month-old Tg and wild type (WT) rats were imaged
      with both [18F]-FP-CMT, a dopamine transporter (DAT) ligand (n=16), and [18F]
      Fallypride, a D2/D3 dopamine receptor (D2/D3DR) ligand (n=16). Five to 8 month
      old Tg and WT rats (n=18) were also imaged with [18F]-FP-CMT. A subset of animals
      was imaged longitudinally at 7 and 17 months of age. Multiplex
      immunohistochemistry staining for DAT, tyrosine hydroxylase, D2DR, D3DR, GFAP,
      Iba1 and NeuN was performed on a subgroup of the scanned animals. RESULTS: [18F]
      FP-CMT and [18F]-Fallypride binding potential (BPND) values were significantly
      lower in 15-18 month-old Tg compared to age-matched WT rats (p<0.0001 and 0.001,
      respectively). [18F]-FP-CMT BPND values in 5-8 month-old rats, however, were not
      significantly different. Longitudinal age-related decrease in [18F]-FP-CMT BPND
      was exacerbated in the Tg rat. Immunohistochemistry showed decreased staining of
      dopaminergic markers in Tg rats. Rats with higher serum gp120 had lower mean BPND
      values for both ligands. CONCLUSIONS: We found presynaptic and postsynaptic
      dopaminergic dysfunction/loss in older Tg compared to WT rats. We believe this to
      be related to neurotoxicity of viral proteins present in the Tg rats' serum and
      brain. ADVANCES IN KNOWLEDGE: Our findings confirm prior reports of
      neurobehavioral abnormalities suggestive of dopaminergic dysfunction in this
      model. They also suggest similarities between the Tg rat and HIV+ patients as far
      as dopaminergic dysfunction. IMPLICATIONS FOR PATIENT CARE: The Tg rat, along
      with the above-described quantitative PET imaging biomarkers, can have a role in
      the evaluation of HIV neuroprotective therapies prior to human translation.

PMID- 29031115
TI  - Decolorization and detoxification of dye mixture and textile effluent by lichen
      Dermatocarpon vellereceum in fixed bed upflow bioreactor with subsequent
      oxidative stress study.
AB  - Navy Blue HE22 (NBHE22), dye mixture and real textile effluent were decolorized
      and degraded by lichen Dermatocarpon vellereceum. Up-flow bioreactor showed about
      80%, 70%, 80% and 65% removal of American dye manufacturer index (ADMI),
      biological oxygen demand (BOD), total suspended solids (TSS) and total dissolved
      solids (TDS), respectively of dye mixture at flow rate of 25mlh-1. The removal of
      ADMI, BOD, TSS and TDS of real textile effluent were 75%, 65%, 82% and 70%,
      respectively at flow rate of 30mlh-1. Significant induction of extracellular
      enzymes such as manganese peroxidase and lignin peroxidase was observed up to 46%
      and 36% during decolorization of dye mixture, while 43% and 24% during effluent
      treatment, respectively. Exponential enhancement in the activities of stress
      enzymes such as catalase (CAT) and guaiacol peroxidase (GPX) was observed after
      exposure to NBHE22 (116% and 125%, respectively), dye mixture (150% and 300%,
      respectively) and effluent (400% and 350%, respectively) endorsing the stress
      tolerance ability of model lichen. Phytotoxicity and genotoxicity studies
      demonstrated less toxic nature of metabolites resulted from biodegradation.

PMID- 29031116
TI  - Evaluation of fluoride bioremediation and production of biomolecules by living
      cyanobacteria under fluoride stress condition.
AB  - Application of microalgae for defluoridation has gained interest in recent years.
      In the present study, bioremediation of fluoride using living cyanobacteria,
      Starria zimbabweensis, collected from wastewater of coke-oven effluent treatment
      plant, Durgapur, India, has been investigated. Initially, the cyanobacterial
      strain was grown in BG11 medium at 25 degrees C, 45MUmol/m2/s irradiation in 18h:
      6h light:dark cycle in an algal incubator. Samples were withdrawn after 2 days
      interval and analyzed for its dry biomass and lipid content. Optimum inoculum
      size of 10% and age of 16th day were assessed based on maximum dry biomass (9.307
      +/- 0.01g/L) and lipid (244.05 +/- 0.02mg/L) production. SEM-EDX and FTIR studies
      of both native and fluoride treated biomass were done to emphasize the changes.
      During kinetic study of defluoridation, initial fluoride concentration was varied
      in the range of 10-50mg/L. Maximum fluoride removal (66.6 +/- 0.11%) and dry
      biomass (18.19 +/- 0.12g/L) were obtained at 10mg/L fluoride concentration using
      10% of 16th day's inoculum. Biomass and lipid content were found to increase 2
      and 4 folds, respectively under fluoride stress condition. Furthermore,
      chlorophyll, carbohydrate and protein content of the biomass were also compared
      between control and fluoride contaminated conditions. Fatty Acid Methyl Ester
      (FAME) analysis was done using Gas Chromatography (GC) to compare the lipid
      profile of native and fluoride loaded strain.

PMID- 29031117
TI  - Reactions of Melolontha hippocastani adults to high manganese content in food.
AB  - Rapid adaptation of insect species to environmental changes can be advantageous
      for their development. Forest cockchafer (Melolontha hippocastani) is herbivorous
      insect species with high food intake that has been widely studied within European
      conditions. It can cause huge economic and ecological losses especially in oak
      dominated forest stands. Food preference of this species is mainly comprised of
      trees with a potential to accumulate manganese in their assimilation apparatus.
      In order to determine cockchafer's reactions to increased Mn concentration in its
      food, the adults were reared in laboratory conditions controlled for temperature,
      humidity, and light on a natural diet of oak (Quercus petraea) leaves. Food was
      contaminated by soaking in solutions of MnCl2.4H2O in concentrations from 0.5 to
      10mgml-1. Food consumption, activity period of adults, quantity of eggs laid,
      body weights of individuals, as well as Mn concentrations in unconsumed food,
      excrement, and the bodies of cockchafers were determined to indicate how these
      change in reaction to food quality altered in terms of Mn content. The results
      showed that very high Mn content in the diet significantly influenced food
      consumption by M. hippocastani adults and thereby their development. This was in
      spite of the tendency of individuals to expel Mn through the faeces and
      incorporate it into undetermined parts of their bodies. Negative reactions of the
      experimental population were determined in treatments fed leaves with Mn
      concentration of 1800ppm and more. Our experiment proved that Mn can greatly
      influence the phytophagous cockchafer (decreased feeding time, food consumption,
      and fertility).

PMID- 29031118
TI  - Chemical elements in Mediterranean macroalgae. A review.
AB  - This review analyzes the state of knowledge on the capacity of Mediterranean
      macroalgae to accumulate, tolerate and biomonitor macro- and micro-elements
      present in seawater and sediments. The results show that the investigated
      macroalgal species amount to c. 5.0% of all Mediterranean native Rhodophyta,
      Chlorophyta and Ochrophyta. The most commonly analyzed elements in algae were Pb,
      Cd, Zn and Cu, whereas very few studies were available for macroelements such as
      Ca and K. Uptake mechanisms and the factors influencing accumulation are overall
      well known, but the available studies are restricted to a limited number of
      chemical elements and algal species. This review also shows that macroalgae can
      accumulate and tolerate high concentrations of chemical elements, and can act as
      effective bioindicators of marine pollution. Phytotoxic limits for algal species
      are not clearly identified by the available studies and require further
      investigation. Future research should focus on the development of protocols for
      long-term biomonitoring programmes through the use of macroalgae. Future studies
      also need to investigate the biomagnification of toxic trace elements in
      macroalgae-based food webs.

PMID- 29031119
TI  - Index analysis and human health risk model application for evaluating ambient air
      heavy metal contamination in Chemical Valley Sarnia.
AB  - The impacts of air emissions as a consequence of industrial activities around
      communities of human habitation have been extensively reported. This study is the
      first to assess potential adverse human health effects in the Chemical Valley
      Sarnia (CVS) area, around the St. Clair River, using health risk models,
      ecological and pollution indices. Large quantities of particulate matters (PM)
      are generated from anthropogenic activities, which contain several heavy metals
      in trace quantities with potentially adverse effects to humans and environmental
      health. The distribution, and human health impact assessment of trace element
      concentrations in PM fractions were examined. Elemental concentrations of As, Cd,
      Cr (VI), Cu, Fe, Mn, Pb, Ni, Zn were determined in the PM size-segregated samples
      collected from the CVS area between 2014 and 2017. The results showed relatively
      high concentration of PM<2.5 (87.19+/-8.1(mgm3)) which is approximately 4 times
      the WHO air quality guidelines. Pb concentration (143.03 +/- 46.87etag/m3) was
      3.6 times higher than the air quality standards of NAAQS. Cr (VI) showed moderate
      to considerable contamination ( Cf=4) in the CVS while Cr (VI), Pb, and Ni had
      enrichment factor Ef < 3 (minimal), signifying contributions from anthropogenic
      activities. Pollution load index (PLi) value observed was 1.4 indicating human
      health risk from the PM, especially for the children in the area. The deposition
      fluxes (DPhi) showed that PM-bound metals could potentially bypass the head
      airways and cause damages to the tracheobronchial tree, increasing the human
      health risks of nephroblastomasis development. The main route of entry for the
      heavy metal bound PM in humans were observed as through ingestion and inhalation.
      The highest total excess cancer risks observed for children (6.7*10-4) and adult
      (1.0*10-4) indicating potential cancer effects. The Incremental Lifetime Cancer
      Risk (ILCR) increased from Pb < Ni < Cd < Cr (VI) < As. Overall, children are
      more likely to develop carcinogenic and non-carcinogenic health effects from
      exposures to elemental concentrations of airborne PM in the study area.

PMID- 29031120
TI  - Enabling spontaneous analogy through heuristic change.
AB  - Despite analogy playing a central role in theories of problem solving, learning
      and education, demonstrations of spontaneous analogical transfer are rare. Here,
      we present a theory of heuristic change for spontaneous analogical transfer,
      tested in four experiments that manipulated the experience of failure to solve a
      source problem prior to attempting a target problem. In Experiment 1,
      participants solved more source problems that contained an additional financial
      constraint designed to signal the inappropriateness of moves that maximized
      progress towards the goal. This constraint also led to higher rates of
      spontaneous analogical transfer to a superficially similar problem. Experiments 2
      and 3 showed that the effects of this constraint extend to superficially and
      structurally different analogs. Experiment 4 generalized the finding to a non
      analogous target problem that also benefitted from inhibiting maximizing moves.
      The results indicate that spontaneous transfer can arise through experience
      during the solution of a source problem that alters the heuristic chosen for
      solving both analogical and non-analogical target problems.

PMID- 29031121
TI  - Facilitating decision-making in women undergoing genetic testing for hereditary
      breast cancer: BRECONDA randomized controlled trial results.
AB  - BACKGROUND: Decision-making concerning risk-reducing mastectomy for women at
      hereditary risk of breast cancer entails complex personal choices. Deciding
      whether and how to restore breast shape after risk-reducing mastectomy is a key
      part of this process. We developed a web-based decision aid, BRECONDA (Breast
      Reconstruction Decision Aid), to assist women in decision-making regarding breast
      reconstruction. METHOD: This study assessed the efficacy of BRECONDA to assist
      women at increased risk of breast cancer in making decisions regarding risk
      reducing mastectomy in terms of decisional conflict, knowledge, and satisfaction
      with information. Women at hereditary risk of breast cancer (N = 64) were
      recruited into this randomized controlled trial from four Australian hereditary
      cancer clinics. Participants initially provided online consent and completed
      baseline questionnaires assessing decisional conflict, knowledge, and
      satisfaction with information. They were then randomly assigned to either: 1)
      Intervention - unlimited access to BRECONDA, with usual care; or, 2) Control -
      usual care. At 2-months follow-up (N = 60) the outcomes were re-assessed.
      Intervention participants also completed user acceptability ratings for the
      intervention overall and specific key modules. RESULTS: MANCOVA analyses
      indicated that Intervention participants reported lower decisional conflict (P =
      0.027), and greater knowledge (P = 0.019) and satisfaction with information (P <
      0.0005) at 2-months follow-up compared with Controls. Intervention participants
      reported high user acceptability and satisfaction with the intervention.
      CONCLUSION: BRECONDA benefits women considering risk-reducing mastectomy by
      reducing decisional conflict, and improving knowledge and satisfaction with
      information. These benefits, coupled with high user acceptability, demonstrate
      the feasibility of implementing BRECONDA in the hereditary cancer risk context.

PMID- 29031122
TI  - Allocating effort and anticipating pleasure in schizophrenia: Relationship with
      real world functioning.
AB  - BACKGROUND: Poor motivation to engage in goal-oriented behavior has been
      recognized as a hallmark feature of schizophrenia spectrum disorders (SZ). Low
      drive in SZ may be related to anticipating rewards as well as to poor working
      memory. However, few studies to date have examined beliefs about self-efficacy
      and satisfaction for future rewards (anticipatory pleasure). Additionally, few
      studies to date have examined how these deficits may impact SZ patients' real
      world functioning. METHOD: The present study examined SZ patients' (n=57)
      anticipatory pleasure, working memory, self-efficacy and real world functioning
      in relation to their negative symptom severity. RESULTS: Results revealed that SZ
      patients' negative symptom severity was related to decisions in effort allocation
      and reward probability, working memory deficits, self-efficacy and anticipatory
      pleasure for future reward. Effort allocation deficits also predicted patients'
      daily functioning skills. CONCLUSIONS: SZ patients with high levels of negative
      symptoms are not merely effort averse, but have more difficulty effectively
      allocating effort and anticipating pleasure engaging in effortful activities. It
      may be the case that continuously failing to achieve reinforcement from
      engagement and participation may lead SZ patients to form certain negative
      beliefs about their abilities which contributes to amotivation and cognitive
      deficits. Lastly, our findings provide further support for a link between SZ
      patients functional daily living skills their effort allocation.

PMID- 29031123
TI  - Electric field standing wave effects in internal reflection and ATR spectroscopy.
AB  - We investigate electric field standing wave effects in the system semiinfinite
      incidence medium with high index of refraction/layer/vacuum, the latter being the
      semiinfinite exit medium. If the layer has a lower index of refraction than the
      incidence medium, then very strong resonances occur between the two critical
      angles of the system defined by the systems incidence medium/layer and incidence
      medium/vacuum, as the layer is then a cavity. In particular close to the lower
      critical angles, the evanescent fields extend strongly into the exit medium.
      Based on this effect we suggest two new spectroscopic modalities, namely
      interference-enhanced internal reflection Raman spectroscopy and interference
      enhanced attenuated total reflection infrared spectroscopy.

PMID- 29031124
TI  - A relay identification fluorescence probe for Fe3+ and phosphate anion and its
      applications.
AB  - A simple relay identification fluorescence probe for Fe3+ and phosphate anion
      with "on-off-on" switching was designed and synthesized based on the
      phenylthiazole and biphenylcarbonitrile. Probe 1 displayed highly selective and
      sensitive recognition to Fe3+ in HEPES aqueous buffer (EtOH/H2O=2:8, v/v, pH=7.4)
      solutions. The optimized structures and HOMO and LUMO of probe 1 and [1-Fe3+]
      complex were obtained by the density functional theory (DFT) calculations with
      B3LYP as the exchange and correlation functional using a suite of Gaussian 09
      programs. The [1-Fe3+] complex solution also showed a high selectivity toward
      PO43-. The lower limits of detection of probe 1 to Fe3+ and [1-Fe3+] complex to
      PO43- were estimated to 1.09*10-7M and 1.86*10-7M. Besides, the probe 1 also was
      used to detected the target ions in real water sample and living cells
      successfully.

PMID- 29031125
TI  - Low Protein Z levels in patients with plasma cell neoplasms are inversely
      correlated with IL-6 levels.
AB  - : Patients with multiple myeloma (MM) have an increased thrombotic risk, but
      pathogenesis remains uncertain. Low levels of Protein Z (PZ), a vitamin K
      dependent plasma protein, are associated with venous as well as arterial
      thrombosis. The purpose of this study was to analyze PZ levels in patients with
      plasma cell neoplasms. PATIENTS AND METHODS: The study consisted of 64 plasma
      cells neoplasm patients and 42 healthy individuals. Clinical investigations
      included measurement of plasma PZ and IL-6 levels. RESULTS: PZ levels in patients
      with plasma cell neoplasms were significantly lower compared to healthy controls
      in the entire cohort (1392+/-659 vs.2010+/-603ng/mL, P<0.01), as well as in
      specific disease subgroups; symptomatic MM (1428+/-652ng/mL, p<0.01), smoldering
      MM (1437+/-883ng/mL, p=0.045) and monoclonal gammopathy of undetermined
      significance (MGUS) (1247+/-593ng/mL, p=0.01). PZ was negatively correlated with
      IL-6 levels in MM patients (r=-0.7, P<0.01). There was no significant difference
      in PZ levels between patients with or without thrombotic event. CONCLUSION:
      Plasma cell neoplasm patients have low levels of PZ. This is presumably related
      to the increased IL-6 production by the bone marrow microenvironment, and could
      have a potential role in the increased thrombotic tendency in those patients.

PMID- 29031126
TI  - Artesunate induces apoptosis via inhibition of STAT3 in THP-1 cells.
AB  - OBJECTIVE: Our objective was to explore STAT3 expression in patients with acute
      myeloid leukaemia (AML), assess the anti-proliferative effects of artesunate
      (ART) on THP-1 cells in vivo and in vitro, and investigate the underlying
      mechanisms. METHODS: In this study, we examined 30 patients with acute myeloid
      leukaemia diagnosed in our hospital from January 2015 to January 2016. The 20
      control group patients had non-haematological diseases and were hospitalized for
      the same period. We extracted 2ml bone marrow, separated the mononuclear cells,
      obtained total proteins, and detected STAT3 protein levels with Western blot
      analyses. The THP-1 cells were treated with different concentrations of ART(0,
      10, 25, 50, 100, 200MUM). Then, THP-1 cell viability was detected with CCK-8
      assays, apoptosis was measured with flow cytometry, and the STAT3, caspase-3 and
      caspase-8 protein levels were assessed using Western blot analyses. THP-1 cells
      in logarithmic growth phase were subcutaneously injected into the necks of 5-week
      old nude mice. The control group was subcutaneously injected with 0.1ml PBS.
      After the nude mouse tumours grew, the mice were divided into the control group
      and drug intervention groups (ART 100MUM group, ART 200MUM group). The mice in
      the intervention groups were intraperitoneally injected with ART, and the control
      group was injected with the same amount of normal saline. Then, changes in the
      tumours were observed. After the drug intervention, the total protein was
      extracted, and STAT3 expression was detected by Western blot analysis. RESULTS:
      Compared with the control group, the AML patients had significantly increased
      STAT3 protein levels (P<0.01). ART significantly inhibited the proliferation of
      THP-1 cells in a dose-dependent and time-dependent manner. ART also increased THP
      1cell apoptosis. After treatment with ART, STAT3 protein was significantly down
      regulated, and apoptosis of the cells was induced by the activation of caspase-3
      and caspse-8. CONCLUSION: AML patients had higher expression of STAT3 than that
      of the controls. ART induced apoptosis in THP-1 cells and inhibited the growth of
      xenografts in nude mice, and we also observed that ART down-regulated the
      expression of STAT3 and activated the caspase-3 and caspase-8. We speculated that
      the effect of ART on THP-1 cells may be related to inhibition of STAT3 and
      activation of caspase3 and caspase-8.

PMID- 29031127
TI  - Patients' perceptions and experiences of living with a surgical wound healing by
      secondary intention: A qualitative study.
AB  - BACKGROUND: Most surgical wounds heal by primary intention, that is to say, the
      edges of the wound are brought together with sutures, staples, adhesive glue or
      clips. However, some wounds may be left open to heal (if there is a risk of
      infection, or if there has been significant tissue loss), and are known as
      'surgical wounds healing by secondary intention'. They are estimated to comprise
      approximately 28% of all surgical wounds and are frequently complex to manage.
      However, they are under researched and little is known of their impact on
      patients' lives. OBJECTIVES: To explore patients' views and experiences of living
      with a surgical wound healing by secondary intention. DESIGN: A qualitative,
      descriptive approach. SETTINGS: Participants were recruited from acute and
      community nursing services in two locations in the North of England characterised
      by high levels of deprivation and diverse populations. PARTICIPANTS: Participants
      were aged 18 years or older and had at least one surgical wound healing by
      secondary intention, which was slow to heal. Purposeful sampling was used to
      include patients of different gender, age, wound duration and type of surgery
      (general, vascular and orthopaedic). Twenty people were interviewed between
      January and July 2012. METHODS: Semi-structured interviews were conducted, guided
      by use of a topic guide developed with input from patient advisors. Data were
      thematically analysed using steps integral to the 'Framework' approach to
      analysis, including familiarisation with data; development of a coding scheme;
      coding, charting and cross comparison of data; interpretation of identified
      themes. FINDINGS: Alarm, shock and disbelief were frequently expressed initial
      reactions, particularly to "unexpected" surgical wounds healing by secondary
      intention. Wound associated factors almost universally had a profound negative
      impact on daily life, physical and psychosocial functioning, and wellbeing.
      Feelings of frustration, powerlessness and guilt were common and debilitating.
      Patients' hopes for healing were often unrealistic, posing challenges for the
      clinicians caring for them. Participants expressed dissatisfaction with a
      perceived lack of continuity and consistency of care in relation to wound
      management. CONCLUSIONS: Surgical wounds healing by secondary intention can have
      a devastating effect on patients, both physical and psychosocial. Repercussions
      for patients' family members can also be extremely detrimental, including
      financial pressures. Health care professionals involved in the care of patients
      with these wounds face multiple, complex challenges, compounded by the limited
      evidence base regarding cost-effectiveness of different treatment regimens for
      these types of wounds.

PMID- 29031128
TI  - Electrochemically mediated in situ growth of electroactive polymers for highly
      sensitive detection of double-stranded DNA without sequence-preference.
AB  - The ability to directly detect double-stranded DNA (dsDNA) without sequence
      preference continues to be a major challenge. Herein, we report an
      electrochemical method for the direct, highly sensitive detection of dsDNA based
      on the strand replacement of dsDNA by peptide nucleic acid (PNA) and the in situ
      growth of electroactive polymers through the surface-initiated electrochemically
      mediated atom transfer radical polymerization (SI-eATRP). Thiolated PNA molecules
      are firstly self-assembled onto gold electrode surface for the specific
      recognition of target dsDNA (dsDNA-T), which in turn leads to the formation of a
      high density of PNA/DNA heteroduplexes on the electrode surface for the
      subsequent attachment of ATRP initiators via the phosphate-Zr4+-carboxylate
      chemistry. By applying a negative potential to the electrode, the air-stable CuII
      deactivators can be reduced into the CuI activators so as to trigger the surface
      initiated polymerization for the in situ growth of electroactive polymers. Due to
      the strand replacement of dsDNA by PNA, dsDNA can be directly detected without
      sequence-preference. Besides, the growth of polymers enables the modification of
      numerous electroactive probes, thereby greatly improving the electrochemical
      signal. Under optimal conditions, a good linearity between the electrochemical
      signal and the logarithm of dsDNA-T concentration over the range from 1.0 fM to
      1.0nM, with a detection limit of 0.47 fM, can be obtained. Results indicate that
      it is highly selective, and holds high anti-interference capability in the
      presence of human serum samples. Therefore, this method offers great promises in
      providing a universal and efficient solution for the direct detection of dsDNA.

PMID- 29031129
TI  - A dual-type responsive electrochemical immunosensor for quantitative detection of
      PCSK9 based on n-C60-PdPt/N-GNRs and Pt-poly (methylene blue) nanocomposites.
AB  - In this study, a dual-type responsive electrochemical immunosensor was developed
      for the quantitative detection of proprotein convertase subtilisin/kexin type 9
      (PCSK9), a potential biomarker of cardiovascular disease in serum. N-doped
      graphene nanoribbons (N-GNRs) with good conductivity were used as the sensing
      matrix modifying the glassy carbon electrode. Palladium platinum alloy (PdPt)
      nanoparticles with high catalytic performance toward the reduction of hydrogen
      peroxide (H2O2) were reduced onto amino-functionalized fullerene (n-C60-PdPt) and
      significantly amplified the electrochemical signal recorded by the amperometric i
      t curve. Furthermore, staphylococcus protein A (SPA) with antibody orientation
      function was introduced to improve the immunoreaction efficiency. Accordingly, a
      label-free immunosensor was fabricated based on n-C60-PdPt/N-GNRs for the quick
      detection of PCSK9. Meanwhile, to realize ultrasensitive detection of PCSK9, Pt
      poly (methylene blue) (Pt-PMB) nanocomposites synthesized by a one-pot method for
      the first time were used as a novel signal label, which exhibited uniform
      morphology as well as good conductivity and produced an electrochemical signal
      recorded by differential pulse voltammetry (DPV). Herein, a novel sandwich-type
      immunosensor was designed using n-C60-PdPt/N-GNRs as the sensing matrix and Pt
      PMB as the signal label for sensitive detection of PCSK9. Under optimal
      conditions, the label-free immunosensor showed a linear range of 10pgmL-1 to
      100ngmL -1 with a detection limit of 3.33pgmL-1 (S/N=3), and the sandwich-type
      immunosensor exhibited a linear range of 100 fg mL-1 to 100ngmL -1 with a
      detection limit of 0.033pgmL-1 (S/N=3) for PCSK9 detection, indicating its
      potential application in clinical bioassay analysis.

PMID- 29031130
TI  - A Validated Prognostic Biomarker Score for Adult Patients with Nonmetastatic Soft
      Tissue Sarcomas of the Trunk and Extremities.
AB  - BACKGROUND: The prognostic value of serum biomarkers in soft tissue sarcoma (STS)
      is limited, and its clinical applicability is compromised by a common inability
      to adjust for important confounders. The aim of this study was to determine the
      prognostic value of pretreatment biomarkers on disease-specific survival (DSS)
      adjusted for confounders. METHODS: The study included 818 patients with localized
      STS. Pretreatment levels of albumin, C-reactive protein, hemoglobin, neutrophils,
      and lymphocytes were tested individually and combined in prognostic scores:
      neutrophil/lymphocyte ratio (NLR), Glasgow Prognostic Score (GPS), and Aarhus
      Composite Biomarker Score (ACBS) which includes all five biomarkers. Patients
      were randomly split into a test cohort and a validation cohort. The prognostic
      value of biomarkers on DSS was estimated using crude and adjusted Cox
      proportional hazard models. The different biomarker scores were compared using
      Akaike's information criteria. RESULTS: In the test cohort of 403 patients, all
      biomarkers except lymphocyte count were significant prognostic factors for DSS
      also after adjusting for confounders. NLR, GPS, and ACBS were independently
      associated with decreased survival; however, ACBS was significantly superior to
      NLR (P=.02) and GPS (P=.002). These findings were validated in the randomly
      assigned validation cohort of 415 patients. In the pooled data of 818 patients,
      the ACBS performed better than GPS and NLR. ACBS 2 was independently associated
      with decreased DSS compared to ACBS 0, hazard ratio 2.3[95% confidence interval:
      1.5-3.5], P<.001. CONCLUSION: Patients with abnormal values in more than one
      serum biomarkers had a significant additional risk of dying compared to patients
      with only one abnormal value. ACBS was validated as an independent prognostic
      factor that is superior to both NLR and GPS.

PMID- 29031131
TI  - Depression, sleep problems, and perceived stress among informal caregivers in 58
      low-, middle-, and high-income countries: A cross-sectional analysis of community
      based surveys.
AB  - Caregiving has been associated with adverse health outcomes. However, there is a
      paucity of multi-country, population-based studies on mental health outcomes of
      caregivers especially from low- and middle-income countries (LMICs). Thus, we
      assessed the association of caregiving with depression, sleep problems, and
      perceived stress in 10 high-, 27 middle-, and 21 low-income countries. Cross
      sectional community-based data of the World Health Survey including 258,793
      adults aged >=18 years were analyzed. Multivariable logistic and linear
      regression analyses were conducted to explore the association of past 12-month
      caregiving with past 12-month DSM-IV depression, and past 30-day perceived stress
      [range 0 (low)-100 (high)] and severe/extreme sleep problems. Nearly 20% of the
      individuals were engaged in caregiving with particularly high rates observed in
      high-income countries (HICs) (e.g., Finland 43.3%). Across the entire sample,
      after adjustment for potential confounders, caregivers had a significantly higher
      likelihood of having depression (OR = 1.54; 95%CI = 1.37-1.73), sleep problems
      (OR = 1.37; 95%CI = 1.25-1.50), while their mean perceived stress score was 3.15
      (95%CI = 2.46-3.84) points higher. These associations tended to be stronger in
      HICs. A greater number of caregiving activities was associated with a greater
      likelihood of depression, sleep problems, and perceived stress regardless of
      country income levels. In conclusion, caregiving has a negative impact on mental
      health worldwide with possibly greater effects in HICs. Given the growing
      contribution of caregivers in long-term care, interventions and policies to
      alleviate the mental health burden of caregivers are urgently needed to maintain
      sustainable and effective care practices.

PMID- 29031133
TI  - NMR diffusometry data sampling optimization for mixture analysis.
AB  - NMR diffusometry is a powerful but challenging method to analyze complex mixture.
      Each component diffuses differently, from the faster small species to the slower
      large species, corresponding to different signal attenuation. However, the method
      is highly sensitive to the quality of the acquired data and the performance of
      the processing used to resolve multiexponential signals influences. Adapting the
      signal decay sampling to the mixture composition is one way to improve the
      precision of the measure. In this work, we propose a prediction tool, based on
      the calculation of the Cramer-Rao lower bound to minimize the variance of
      diffusion coefficient estimation in order to determine the optimal number of
      diffusion gradient steps, the best diffusion gradient sampling (among linear,
      exponential, quadratic and sigmoidal ones) and the optimal maximum diffusion
      factor. The tool was validated experimentally on a unimer/micelle solution of
      sodium dodecyl sulfate and on Caelyx(r), a commercial liposomal preparation
      containing a mixture of pegylated-liposomes and sucrose.

PMID- 29031132
TI  - Effectiveness of policy changes to reduce harm from unrecorded alcohol in Russia
      between 2005 and now.
AB  - BACKGROUND: Consumption of unrecorded alcohol (alcohol that is not taxed and
      reflected in official statistics, but consumed as a beverage) has been identified
      as one of the main contributors to alcohol-attributable premature mortality in
      Russia. The problem was highlighted by a recent a mass poisoning with surrogate
      alcohol occurred in the Siberian city of Irkutsk. METHODS: Based on key
      publications and legislative documents, a narrative review was undertaken about
      alcohol-related harm reduction policies in Russia for the period between 2005 and
      2017, as well as the impact of these policies on the recorded and unrecorded
      alcohol consumption and alcohol market. RESULTS: Various policy measures mainly
      targeting availability and price of recorded and unrecorded alcohol have been
      introduced since 2005, which generally coincided with the decreases in alcohol
      related mortality observed at that time. However, regulations on medicinal and
      cosmetic products have remained inconsistent providing the foundations for the
      continued existence of a legal industry of surrogates with broad availability and
      misuse. CONCLUSION: The Russian experiences of introducing alcohol policies
      demonstrate that there are effective measures to reduce unrecorded alcohol
      consumption and attributable harm. The government's multi-level strategy of
      alcohol consumption and harm reduction should be pursued stringently and all the
      possible loop-holes for producers, sellers and distributors of illegal and/or
      unrecorded alcohol should be eliminated or at least critically reduced.

PMID- 29031134
TI  - The positive relationships between plant coverage, species richness, and
      aboveground biomass are ubiquitous across plant growth forms in semi-steppe
      rangelands.
AB  - The positive relationships between biodiversity and aboveground biomass are
      important for biodiversity conservation and greater ecosystem functioning and
      services that humans depend on. However, the interaction effects of plant
      coverage and biodiversity on aboveground biomass across plant growth forms
      (shrubs, forbs and grasses) in natural rangelands are poorly studied. Here, we
      hypothesized that, while accounting for environmental factors and disturbance
      intensities, the positive relationships between plant coverage, biodiversity, and
      aboveground biomass are ubiquitous across plant growth forms in natural
      rangelands. We applied structural equation models (SEMs) using data from 735
      quadrats across 35 study sites in semi-steppe rangelands in Iran. The combination
      of plant coverage and species richness rather than Shannon's diversity or species
      diversity (a latent variable of species richness and evenness) substantially
      enhance aboveground biomass across plant growth forms. In all selected SEMs,
      plant coverage had a strong positive direct effect on aboveground biomass (beta =
      0.72 for shrubs, 0.84 for forbs and 0.80 for grasses), followed by a positive
      effect of species richness (beta = 0.26 for shrubs, 0.05 for forbs and 0.09 for
      grasses), and topographic factors. Disturbance intensity had a negative effect on
      plant coverage, whereas it had a variable effect on species richness across plant
      growth forms. Plant coverage had a strong positive total effect on aboveground
      biomass (beta = 0.84 for shrubs, 0.88 for forbs, and 0.85 for grasses), followed
      by a positive effect of species richness, and a negative effect of disturbance
      intensity across plant growth forms. Our results shed light on the management of
      rangelands that is high plant coverage can significantly improve species richness
      and aboveground biomass across plant growth forms. We also found that high
      disturbance intensity due to heavy grazing has a strong negative effect on plant
      coverage rather than species richness in semi-steppe rangelands. This study
      suggests that proper grazing systems (e.g. rotational system) based on carrying
      capacity and stocking rate of a rangeland may be helpful for biodiversity
      conservation, better grazing of livestock, improvement of plant coverage and
      enhancement of aboveground biomass.

PMID- 29031135
TI  - Shared agenda making for quality improvement; towards more synergy in maternity
      care.
AB  - OBJECTIVES: Professionals in maternity care have started working in a network
      approach. To further enhance the efficacy of this multidisciplinary maternity
      network, the identification of priorities for improvement is warranted. The aim
      of this study was to create key recommendations for the improvement agenda, in co
      production with patients and professionals. STUDY DESIGN: We conducted a Delphi
      study to inventory (round 1), prioritize (round 2) and eventually approve (round
      3) the improvement agenda for the maternity network. Both patients and
      professionals joined this study. Initial input for the study consisted of
      experiences from 397 patients, collected using the ReproQ questionnaire. In round
      1, the expert panel, gave improvement recommendations, based on the ReproQ
      results. This resulted in 11 recommendations. In the second round, the expert
      panel prioritised these recommendations. In the consensus meeting then finally
      the concrete improvement agenda was composed. RESULTS: Priority scores differed
      considerably between patients and professionals in seven items, while four items
      received similar priority scores from both groups. The four most important
      improvement activities were: Realise more single bedrooms in hospitals; Create
      more opportunities for the continued presence of the community midwife during
      labour; Initiate a digital patient record view system for the network with a view
      function for patients; and Introduce a case manager for pregnant woman.
      CONCLUSION: Based on patient experience and the active involvement of patients
      and professionals, we were able to compose the shared agenda for quality
      improvement in maternity care.

PMID- 29031136
TI  - Increased sensory noise and not muscle weakness explains changes in non-stepping
      postural responses following stance perturbations in healthy elderly.
AB  - The response to stance perturbations changes with age. The shift from an ankle to
      a hip strategy with increasing perturbation magnitude occurs at lower
      accelerations in older than in young adults. This strategy shift has been related
      to age-related changes in muscle and sensory function. However, the effect of
      isolated changes in muscle or sensory function on the responses following stance
      perturbations cannot be determined experimentally since changes in muscle and
      sensory function occur simultaneously. Therefore, we used predictive simulations
      to estimate the effect of isolated changes in (rates of change in) maximal joint
      torques, functional base of support, and sensory noise on the response to
      backward platform translations. To evaluate whether these modeled changes in
      muscle and sensory function could explain the observed changes in strategy;
      simulated postural responses with a torque-driven double inverted pendulum model
      controlled using optimal state feedback were compared to measured postural
      responses in ten healthy young and ten healthy older adults. The experimentally
      observed peak hip angle during the response was significantly larger (5 degrees )
      and the functional base of support was smaller (0.04m) in the older than in the
      young adults but peak joint torques and rates of joint torque were similar during
      the recovery. The addition of noise to the sensed states in the predictive
      simulations could explain the observed increase in peak hip angle in the elderly,
      whereas changes in muscle function could not. Hence, our results suggest that
      strength training alone might be insufficient to improve postural control in
      elderly.

PMID- 29031137
TI  - The association between habitual walking speed and medial femoral cartilage
      deformation following 30minutes of walking.
AB  - Habitual walking speed is a key functional outcome that has implications for knee
      biomechanics that occur during gait. Lower extremity biomechanics during walking
      affects the loading of the femoral cartilage. Ultrasonography (US) can be used to
      assess resting femoral cartilage thickness and acute cartilage deformation in
      response to walking. The purpose of this study was to determine the association
      between habitual walking speed and both resting femoral cartilage thickness and
      deformation. Twenty-four healthy participants with no history of knee injury
      volunteered for this study. Habitual walking speed was assessed with a 20-m walk
      test. Femoral cartilage thickness was assessed with US in the medial condyle,
      lateral condyle, and intercondylar regions prior to and immediately following
      30min of walking. Femoral cartilage deformation was calculated as the percent
      change in cartilage thickness acutely following the walking protocol. Separate
      Pearson product moment correlations were used to assess the association between
      habitual walking speed and each US cartilage variable. Slower habitual walking
      speed was significantly associated with greater medial femoral cartilage
      deformation (r=0.48, P=0.018), but not with lateral and intercondylar
      deformation. Habitual walking speed was not significantly associated with the
      resting cartilage thickness in any cartilage region. These findings highlight the
      in vivo association between walking speed and medial femoral cartilage
      deformation. When controlling for body mass index, the association between
      walking speed and medial cartilage deformation was weakened (Deltar=-0.12).
      Future studies are needed to determine the extent to which BMI influences the
      association between walking speed and cartilage deformation.

PMID- 29031138
TI  - Similarity of muscle synergies extracted from the lower limb including the deep
      muscles between level and uphill treadmill walking.
AB  - This study aimed to examine muscle synergies involving the deeper muscles of the
      lower limb during level and uphill treadmill walking. Seven men and five women
      walked on a treadmill at three speeds (60, 80, and 100m/min) and two grades
      (level and 10% grade). Surface electromyographic (EMG) signals were recorded from
      10 muscles of the lower limb, including vastus intermedius, adductor magnus, and
      adductor longus. Muscle synergies were extracted applying non-negative matrix
      factorization, and the relative co-activation across muscles and the temporal
      information of synergy recruitment were identified by the muscle synergy vector
      and synergy activation coefficient, respectively. Correlation coefficients
      between a pair of synergy vectors during level and uphill walking were analyzed
      as a similarity index, with the similarity criterion at r=0.76. Changes in
      synergy activation coefficients between the walking conditions were evaluated by
      cross-correlation analysis. The mean number of synergies ranged from 3.8 to 4.0
      across all conditions, and they were not significantly different between level
      and uphill walking conditions. Similarity between walking conditions was high
      (r>0.76) for three muscle synergies, but not for one synergy that mainly
      consisted of the quadriceps femoris. The inter-condition similarity of the
      synergy activation coefficients was high for the four synergies, and a
      significant lag time for synergy 2, which consisted mainly of the activity of
      medial gastrocnemius, was found at 60 and 80m/min. The muscle synergies extracted
      from the lower limb involving the deeper muscles appear to be consistent during
      level and uphill treadmill walking.

PMID- 29031139
TI  - Biomechanics of the infant foot during the transition to independent walking: A
      narrative review.
AB  - Recognising structural and functional development of the paediatric foot is
      fundamental to ensuring a strong theoretical framework for health professionals
      and scientists. The transition of an infant from sitting to walking takes
      approximately 9 months and is when the structures and function of the foot must
      respond to the challenges of bearing load; becoming increasingly more essential
      for locomotion. Literature pertaining to the phase of development was searched. A
      narrative approach synthesised the information from papers written in English,
      with non-symptomatic infant participants up to the development stage of
      independent walking or two years of age. A range of literature was identified
      documenting morphological, physiological, neuromuscular and biomechanical aspects
      of the infant within this phase of development. The progression of variable gait
      to a regular pattern is documented within a range of studies focusing on
      neuromuscular control and ambulation development. However, methodological
      approaches may have compromised the external validity of such data. Additionally,
      limited consideration for the specific function and development of the foot is
      evident, despite its role as the primary site of weight bearing and interface
      with the floor. A lack of consideration of infants prior to ambulation (i.e.
      before cruising or walking) is also apparent which prevents a reference baseline
      being used effectively. This review also identifies future research priorities
      such that a comprehensive understanding of foot development from a non-weight
      bearing to a weight bearing structure during locomotor advancement can be gained.

PMID- 29031140
TI  - The effects of real and artificial Leg Length Discrepancy on mechanical work and
      energy cost during the gait.
AB  - BACKGROUND: The impacts of Leg Length Discrepancy (LLD) on the kinematic and
      dynamic parameters of walking have been widely discussed. But little is known on
      total mechanical work and energy cost. These two variables are more
      representative of the functional impairment undergone by the LLD patients. AIM:
      To assess the changes of the mechanical work and energy cost of walking in
      subjects with real LLD and to compare their results with healthy subjects in whom
      the LLD has been simulated. METHOD: The mechanical work and energy cost data of
      60 healthy subjects (speed: 4km/h) with artificial LLD induced by soles (2 and
      4cm), 20 patients (speed: 3.75+/-0.5km/h) with real LLD and 20 matched subjects
      (speed: 3.75+/-0.5km/h) were collected. Statistical comparisons between the
      groups were performed using a t-paired test and ANOVA. RESULTS: Patients with a
      real LLD showed a significant decrease in mechanical work and energy cost when
      compared to norms. Patients with real LLD provide a better recovery when compared
      to subjects with artificial LLD of 2cm, and a decrease of energy cost and higher
      muscular efficiency (mechanical work/energy cost) when compared to subjects with
      artificial LLD of 4cm. CONCLUSIONS: Our results showed that patients with a real
      LLD develop compensatory strategies during gait, probably to minimize the
      displacement of the body center of mass and consequently reduce the amount of
      energy expenditure useful for their displacement. Moreover, they adopt a better
      gait strategy compared to the subjects in whom LLD was simulated.

PMID- 29031141
TI  - Analysis of spastic gait in cervical myelopathy: Linking compression ratio to
      spatiotemporal and pedobarographic parameters.
AB  - BACKGROUND: Gait dysfunction associated with spasticity and hyperreflexia is a
      primary symptom in patients with compression of cervical spinal cord. The
      objective of this study was to link maximum compression ratio (CR) to
      spatiotemporal/pedobarographic parameters. METHODS: Quantitative gait analysis
      was performed by using a pedobarograph in 75 elderly males with a wide range of
      cervical compression severity. CR values were characterized on T1-weighted
      magnetic resonance imaging (MRI). Statistical significances in gait analysis
      parameters (speed, cadence, stride length, step with, and toe-out angle) were
      evaluated among different CR groups by the non-parametric Kruskal-Wallis test
      followed by the Mann-Whitney U test using Bonferroni correction. The Spearman
      test was performed to verify correlations between CR and gait parameters.
      RESULTS: The Kruskal-Wallis test revealed significant decline in gait speed and
      stride length and significant increase in toe-out angle with progression of
      cervical compression myelopathy. The post-hoc Mann-Whitney U test showed
      significant differences in these parameters between the control group (0.45<CR)
      and the worst myelopathy group (CR<=0.25). Cadence and step width did not
      significantly change with CR. On the other hand, the Spearman test revealed that
      CR was significantly correlated with speed, cadence, stride length, and toe-out
      angle. CONCLUSION: Gait speed, stride length, and toe-out angle can serve as
      useful indexes for evaluating progressive gait abnormality in cervical
      myelopathy. Our findings suggest that CR<=0.25 is associated with significantly
      poorer gait performance. Nevertheless, future prospective studies are needed to
      determine a potential benefit from decompressive surgery in such severe
      compression patients.

PMID- 29031142
TI  - Protective effects of Schisandrin B on cigarette smoke-induced airway injury in
      mice through Nrf2 pathway.
AB  - Schisandrin B (SchB), a dibenzocyclooctadiene derivative isolated from Schisandra
      chinensis, has been reported to have anti-inflammatory effects. However, the
      protective effects of SchB on cigarette smoke (CS)-induced lung inflammation
      remain unclear. This study was to investigate the effects of SchB on CS-induced
      lung inflammation in mice. The mice were exposed to CS to develop lung
      inflammation. SchB was given 1h before CS exposure daily for five consecutive
      days. The levels of inflammatory mediators TNF-alpha, IL-1beta, and IL-6 in
      bronchoalveolar lavage fluid (BALF) were measured in this study. SOD, GSH, MPO
      and MDA contents were also detected. Furthermore, the expression of Nrf-2 and NF
      kappaB were detected by western blot analysis. Histopathological analyses showed
      that SchB had protective effects against CS-induced lung inflammation. The levels
      of inflammatory mediators TNF-alpha, IL-1beta, and IL-6 in BALF were also
      inhibited by SchB. CS-induced MPO activity and MDA content were inhibited by
      SchB. The levels of SOD and GSH were up-regulated by SchB. SchB significantly
      inhibited CS-induced NF-kappaB activation and up-regulated the expression of Nrf2
      and HO-1. In conclusion, these data suggest that SchB protects against CS-induced
      lung inflammation by activating Nrf2 and inhibiting NF-kappaB signaling pathway.

PMID- 29031143
TI  - C5a/C5aR pathway accelerates renal ischemia-reperfusion injury by downregulating
      PGRN expression.
AB  - Recent reports indicate that the complement C5a/C5aR pathway and progranulin
      (PGRN) deficiency both contribute to ischemia-reperfusion (IR)-induced acute
      kidney injury. However, the underlying relationship between the C5a/C5aR
      signaling pathway and PGRN expression during acute kidney injury is poorly
      understood. In this study, we showed that C5aR expression was significantly
      upregulated after renal IR, and that C5aR deficiency led to a marked increase in
      PGRN expression and a significant reduction in tubular damage and production of
      inflammatory cytokines. In accordance with these results, recombinant C5a caused
      downregulation of PGRN protein and mRNA levels in renal tubular epithelial cells
      (HK-2 cells), which could be negated by disruption of C5a/C5aR signaling by the
      C5aR antagonist, as confirmed by immunofluorescence, western blotting, and
      quantitative real-time PCR. Moreover, C5aR deficiency resulted in attenuated NF
      kappaB expression 24h after IR, and recombinant C5a potentiated TNFalpha-induced
      NF-kappaB activation in HK-2 cells. Inhibition of NF-kappaB activation reversed
      C5a-induced downregulation of PGRN expression. Our results show for the first
      time that the complement C5a/C5aR pathway aggravates IR-induced acute kidney
      injury by suppressing PGRN expression and confirm that suppression of PGRN
      expression is associated with increased NF-kappaB activation induced by C5a.

PMID- 29031144
TI  - Senegenin exerts anti-depression effect in mice induced by chronic un-predictable
      mild stress via inhibition of NF-kappaB regulating NLRP3 signal pathway.
AB  - Depressive disorder is a kind of affective disturbance disease. Emerging evidence
      has suggested that inflammation may contribute to the pathologic process of
      depressive disorder. Senegenin (SEN), a major bioactive constituent in Polygala
      tenuifolia Willd, has much bioactivity including anti-inflammatory and
      neuroprotection effects. However, the mechanism of its anti-depressant effect in
      mice remains unknown. This study aimed to explore the anti-depressant effects of
      SEN on behavioral changes and inflammatory responses in mice induced by chronic
      un-predictable mild stress (CUMS). SEN treatment remarkably ameliorated CUMS
      induced behavioral abnormalities, such as improving locomotor activity,
      decreasing immobility time in Tail suspension test (TST) and Forced swimming test
      (FST), and increasing sucrose intake in Sucrose preference test (SPT).
      Additionally, SEN improve protein levels of Brain-derived neurotrophic factor
      (BDNF) and Neurotrophin-3 (NT-3) expression. In response to stress, p65 was
      activated to promote production of pro-IL-1beta, and then cleaved to mature IL
      1beta by NOD-like receptor protein 3 (NLRP3) inflammasome pathway in hippocampus
      of CUMS mice. After SEN treatment, protein activation related to NLRP3
      inflammasome pathway was down-regulated, which inhibited IL-1beta secretion.
      These results demonstrate that SEN plays an important role in treatment CUMS
      induced depression in mice, possibly via suppression of pathway activation
      associated with NLRP3 inflammasome.

PMID- 29031145
TI  - Small molecule-mediated upregulation of CCR7 ameliorates murine experimental
      autoimmune encephalomyelitis by accelerating T-cell homing.
AB  - Impairing the infiltration of immune cells into the CNS is a promising target for
      suppressing the development of multiple sclerosis (MS) and its animal model
      experimental autoimmune encephalomyelitis (EAE). Here, we found that oral
      administration of a synthetic small molecular compound Fc24 showed potential
      preventive effects on the development of EAE, including the reduction in EAE
      severity and a delay in the onset of the disease. Fc24 facilitated the
      accumulation of both CD4+ and CD8+ T cells within spleen and lymph nodes, while
      having no effect on MOG-specific T cell responses. Furthermore, CCR7 expression
      was upregulated by Fc24 on activated T cells in vivo and in vitro, accompanied by
      ERK activation in the treated T cells in response to CCL19. These findings
      demonstrate that small molecule-mediated CCR7 upregulation might ameliorate EAE
      by facilitating T cell homing into and within lymphoid organs, and that Fc24 may
      be a potential candidate for modifying the development of EAE.

PMID- 29031146
TI  - Facile synthesis of two clay minerals supported graphitic carbon nitride
      composites as highly efficient visible-light-driven photocatalysts.
AB  - To overcome rapid electron-hole recombination and low adsorption capacity of
      single g-C3N4 photocatalyst, the present work reports on the fabrication of two
      kinds of visible-light-driven composite photocatalysts (g-C3N4/kaolinite and g
      C3N4/illite composites). 2D/2D assembly was successfully achieved in this work.
      Furthermore, the as-synthesized composites exhibited significantly enhanced
      photocatalytic activity under visible-light irradiation, whose reaction rate
      constants were almost 4.13 times (g-C3N4/kaolinite) and 3.18 times (g
      C3N4/illite) that of pure g-C3N4. A plausible reaction mechanism over the as
      prepared composite photocatalysts was also proposed based on the experimental
      results obtained. The photocatalytic enhancement of synthesized composites should
      be attributed to the intimate interface contact between g-C3N4 and layered
      minerals, resulting in better dispersion performance, higher charge separation
      efficiency as well as stronger adsorption ability.

PMID- 29031147
TI  - As(III) and As(V) adsorption on nanocomposite of hydrated zirconium oxide coated
      carbon nanotubes.
AB  - Novel hydrated zirconium oxide (ZrO(OH)2) coated carbon nanotubes (CNTs) were
      prepared via a filtration-steam hydrolysis method, and were used to remove
      As(III) and As(V) from drinking water. This adsorbent was characterized by
      Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning
      electron microscope (SEM) and transmission electron microscope (TEM). The
      ZrO(OH)2 coated on the surface of CNTs was amorphous, and the coating thickness
      was in the range of 1-8 nm. The ZrO(OH)2/CNTs nanocomposite showed high
      adsorption for both As(III) and As(V) with the maximum adsorption capacities of
      78.2 and 124.6 mg/g, respectively, according to the Langmuir fitting. The
      adsorption capacities of ZrO(OH)2/CNTs at the equilibrium concentration of 10
      MUg/L were 2.0 mg/g for As(III) and 7.2 mg/g for As(V) at pH 7, much higher than
      those of ZrO(OH)2 nanoparticles. Meanwhile, the adsorption rates of As(III) and
      As(V) on the ZrO(OH)2/CNTs were higher than the ZrO(OH)2 nanoparticles. The spent
      adsorbent can be regenerated by re-coating ZrO(OH)2 as the preparation method,
      and the adsorbed amounts of As(III) and As(V) on the ZrO(OH)2/CNTs changed little
      within six cycles. This ZrO(OH)2/CNTs nanocomposite shows a promising application
      potential for the removal of As(III) and As(V) from drinking water.

PMID- 29031148
TI  - Fabrication of charge reversible graphene oxide-based nanocomposite with multiple
      antibacterial modes and magnetic recyclability.
AB  - In this work, N-alkylated poly (4-vinylpyridine) (NPVP), a cationic polymer, was
      firstly applied for the surface modification of Fe3O4 nanoparticles. Then the
      modified Fe3O4 nanoparticles (Fe3O4@NPVP NPs) combined with graphene oxide (GO)
      through simple electrostatic binding. Subsequently, deposited Ag nanoparticles
      (Ag NPs) procedure was carried out to form the multiple antibacterial
      nanocomposites (GO-Fe3O4@NPVP-Ag). The synthesized nanostructures were well
      characterized by Transmission Electron Microscope (TEM), X-ray powder diffraction
      (XRD), Fourier-transform infrared (FT-IR) and Raman spectroscopy. The zeta
      potentialmeasurement showed that the novel antibacterial nanocomposites exhibited
      a capacity of reversing its surface charge from negative (physiological pH) to
      positive (acidic condition). Furthermore, the incorporation of magnetic Fe3O4 NPs
      into the nanosystems facilitates the cyclic utilization of GO-Fe3O4@NPVP-Ag by
      magnetic separation. The antibacterial properties of GO-Fe3O4@NPVP-Ag
      nanocomposites were evaluated with Gram-negative Escherichia coli and Gram
      positive Staphylococcus aureus. Moreover, the cytotoxicity of GO-Fe3O4@NPVP-Ag
      nanocomposites was studied using NIH-3T3 cells. The results showed that the GO
      Fe3O4@NPVP-Ag nanocomposites exhibited excellent antibacterial properties and low
      cytotoxicity, thus confirming its application as a promising rapid bactericide in
      various antibacterial fields.

PMID- 29031149
TI  - Highly efficient photocatalysis toward tetracycline of nitrogen doped carbon
      quantum dots sensitized bismuth tungstate based on interfacial charge transfer.
AB  - In this study, a novel N-CQDs/Bi2WO6 was synthesized through a facile
      hydrothermal method. Multiple techniques were applied to investigate the
      structures, morphologies, optical and electronic properties and photocatalytic
      performance of as-prepared samples. The results indicated that the hybrid
      materials were formed with N-CQDs attached on the surface of sphere-like Bi2WO6.
      The photocatalytic activity of N-CQDs/Bi2WO6 materials was evaluated sufficiently
      by using tetracycline (TC) as target organic pollutant. N-CQDs/Bi2WO6-5 displayed
      superior photocatalytic efficiency with nearly 97% removal of TC in 25min and
      86.37% mineralization in 90min. The degradation reaction coefficient (kobs) was
      approximately two times higher than pure Bi2WO6 as a result of the synergistic
      effects of N-CQDs and Bi2WO6. Increased light harvesting capacity, excellent
      electron transfer ability and improved molecular oxygen activation ability were
      obtained in N-CQDs/Bi2WO6 hybrid materials caused by N-CQDs. The present study
      demonstrated that N-CQDs modification was an effective way to improve
      photocatalytic efficiency, which can be extended to a general strategy for other
      semiconductors. The study indicated that novel N-CQDs/Bi2WO6 has a great
      potential for rapid and efficient treatment of organic pollutants in water.

PMID- 29031151
TI  - Fabrication of green dye-sensitized solar cell based on ZnO nanoparticles as a
      photoanode and graphene quantum dots as a photo-sensitizer.
AB  - Zero-dimensional graphene quantum dots (GQDs) consist of single- or few-layer
      graphene with a size less than 20 nm and stand for a new type of QDs with unique
      properties combining the graphene nature and size-resulted quantum effects. GQDs
      possess unique optical and electronic properties, and in particular possess a
      band-gap less than 2.0 eV because of quantum confinement and edge effects. In
      this study, we investigated the performance of DSSCs using different thicknesses
      of ZnO nanoparticles as a photo-anode and GQDs as a green photosensitizer. The
      current voltage (I-V) test results indicate that the performance of DSSCs is
      improved by increasing the thickness of the photo-anode and the thickness of 40
      MUm shows the highest efficiency for DSSC device based on ZnO nanoparticles photo
      anodes. The DSSC using ZnO nanoparticles as a photo-anode with thickness of 40
      MUm shows almost same efficiency when we replaced N-719 with GQDs which is
      confirmed that using GQDs as an alternative to ruthenium based dyes is a new
      approach for DSSCs.

PMID- 29031150
TI  - The construction of carbon-coated Fe3O4 yolk-shell nanocomposites based on volume
      shrinkage from the release of oxygen anions for wide-band electromagnetic wave
      absorption.
AB  - The demand for microwave absorbing materials with strong absorption capability
      and wide absorption band is increasing due to serious electromagnetic
      interference issues and defense stealth technology needs. Here the carbon-coated
      Fe3O4 (Fe3O4@C) yolk-shell composites were successfully synthesized in a large
      scale for the application of microwave absorption through an in-situ reduction
      process from carbon-coated gamma-Fe2O3 precursor. The results show that the Fe3O4
      nanoparticles are uniformly coated with a thin carbon layer about 10nm in
      thickness and a clear void about 1 nm in width between Fe3O4 core and carbon
      shell are formed due to the volume shrinkage during the reduction treatment. The
      obtained yolk-shell composites exhibit excellent microwave absorption properties.
      The absorption bandwidth with RL values exceeding -10dB is up to 5.4GHz for the
      absorber with a thickness of 2.2mm. The optimal RL can reach up to -45.8dB at
      10.6GHz for the composite with a thickness of 3.0mm. The outstanding microwave
      absorption properties may be attributed to the multiple interfacial polarization,
      good impedance match and multiple reflections and scattering owing to the unique
      yolk-shell structures.

PMID- 29031152
TI  - Transferrin modified ruthenium nanoparticles with good biocompatibility for
      photothermal tumor therapy.
AB  - In the past two decades, there were various kinds of photothermal agents being
      synthesised and investigated for their photothermal effect in antitumor
      applications. However, it is barely reported that the photothermal effect of
      Ruthenium (Ru) nanoparticles was researched in depth. In this work, we introduced
      Ru nanoparticles which possess excellent biocompatibility and metabolize easily
      to the photothermal therapy field. In addition, to improve the cells capacity of
      absorbing Ru nanoparticles, these Ru nanoparticles were modified by transferrin
      (Tf-RuNPs). Subsequently, as is expected, the RuNPs exhibit a remarkably
      integrated and high-quality photothermal property. On the other hand, it is
      significantly that Tf modification could also strengthen the cells absorptive
      ability to uptake Ru nanoparticles through endocytosis., Furthermore, both the in
      vitro cell ablation and in vivo tumor treatment verified that the Tf-RuNPs became
      ideal photothermal agents for photothermal tumor ablation therapy owing to their
      low toxicity and high cell destruction capability.

PMID- 29031153
TI  - Facile displacement of citrate residues from gold nanoparticle surfaces.
AB  - The stability of citrate-residues on gold nanoparticles (AuNPs) against ligand
      displacement has been controversial. Using AuNPs synthesized with deuterated
      citrate in combination with in-situ surface-enhanced Raman spectroscopic (SERS)
      analysis, we report that both citrate-residues and solution impurities can be
      simultaneously adsorbed onto citrate-reduced AuNPs in solution. The citrate
      residues can be readily displaced from AuNPs by organosulfur such as organothiols
      (RS-H), organodisuflide (R-S-S-R), and non-specific ligands including halides and
      adenine. Control experiments conducted on high-purity gold films sputter-coated
      onto silicone substrates indicate that air-borne and solvent-borne impurities
      rapidly contaminate the gold surfaces. Head-to-head comparison of ligand
      functionalized AuNPs by in-situ SERS measurements verses those from the ex-situ X
      ray photoelectron spectroscopic (XPS) measurements reveal that the impurity
      deposition can compromise the reliability of ex-situ XPS identification of
      surface adsorbates on AuNPs in solution. These insights are of general
      significance to nanoscience research given the broad interest in nanoparticle
      surface chemistry and popularity of XPS for nanomaterial characterizations.

PMID- 29031154
TI  - Thermally stable microemulsions comprising imidazolium based surface active ionic
      liquids, non-polar ionic liquid and ethylene glycol as polar phase.
AB  - Ionic liquid (IL), 1-ethyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)imide, [C2mim] [Tf2N], as a non-polar phase in
      conjunction with polar ethylene glycol (EG) forms microemulsions stabilized by
      surface active ionic liquids (SAILs), N-methyl-N-alkylimidazolium chlorides,
      [Cnmim] [Cl], where n = 8, 12 and 16 in conjunction with decanol as co
      surfactant. The phase behaviour of the ternary systems has been investigated and
      three regions of microemulsions - polar-in-ionic liquid, bicontinuous and ionic
      liquid-in-polar, have been identified using electrical conductivity measurements.
      The effect of alkyl chain length on the phase behavior has been discussed in
      detail. The one-phase microemulsion region is found to decrease with the increase
      in the alkyl chain length of the SAILs. The microstructural characteristics have
      been investigated by using FTIR and NMR spectroscopy. The micropolarity of
      reverse micelles present in the microemulsions has been investigated using UV-Vis
      spectroscopy employing methyl orange as a polarity probe. The dynamics of solvent
      relaxation in microemulsions have been investigated by steady-state and time
      resolved fluorescence spectroscopy using coumarin 153 (C-153) as fluorescence
      probe at different compositions of microemulsions. The dynamic light scattering
      measurements (DLS) reveals the expansion of reverse micelles formed by
      [Cnmim][Cl] in non polar [C2mim] [Tf2N] upon the addition of polar component.
      Interestingly, the microemulsions have been found to be thermally stable in a
      wide temperature range as revealed from temperature dependence UV-Vis,
      fluorescence and DLS measurements.

PMID- 29031155
TI  - The effect of nanoparticle aggregation on surfactant foam stability.
AB  - The combination of nanoparticles (NPs) and surfactant may offer a novel technique
      of generating stronger foams for gas mobility control. This study evaluates the
      potential of silica NPs to enhance the foam stability of three nonionic
      surfactants. Results showed that the concentration of surfactant and NPs is a
      crucial parameter for foam stability and that there is certain concentrations for
      strong foam generation. A balance in concentration between the nonionic
      surfactants and the NPs can enhance the foam stability as a result of forming
      flocs in solutions. At fixed surfactant concentration, the addition of NPs at low
      to intermediate concentrations can produce a more stable foam compared to the
      surfactant. The production of small population of flocs as a result of mixing the
      surfactant and NPs can enhance the foam stability by providing a barrier between
      the gas bubbles and delaying the coalescence of bubbles. Moreover, these flocs
      can increase the solution viscosity and, therefore, slow the drainage rate of
      thin aqueous film (lamellae). The measurements of foam half-life, bubble size,
      and mobility tests confirmed this conclusion. However, the addition of more solid
      particles or surfactant might have a negative impact on foam stability and reduce
      the maximum capillary pressure of coalescence as a result of forming extensive
      aggregates.

PMID- 29031156
TI  - HIV misdiagnosis: A root cause analysis leading to improvements in HIV diagnosis
      and patient care.
AB  - BACKGROUND: Standard diagnostic testing for HIV infection has traditionally
      relied on a high sensitivity HIV antibody screening test using an enzyme-linked
      immunosorbent assay (ELISA) followed by a high specificity antibody confirmatory
      test such as a Western Blot. Recently several of the screening assays have been
      enhanced with an ability to identify p24 antigen thereby narrowing the diagnostic
      window. OBJECTIVES: To explore the implications of enhanced HIV screening methods
      that may be leading to HIV misdiagnoses. STUDY DESIGN: A patient deemed to be an
      HIV infected 'elite controller' was found to be misdiagnosed when undergoing
      detailed investigations prior to initiating antiretroviral therapy. A root cause
      analysis was performed to identify the causative factors of this misdiagnosis. A
      retrospective review of all "elite controllers" in Alberta, Canada revealed
      challenges of current HIV testing algorithms. RESULTS: Technical and human
      factors were identified as being causative in this HIV misdiagnosis including (i)
      high rates of false reactive results on the Abbott ARCHITECT HIV-1&2 COMBO EIA,
      (ii) human error in reading the initial Western blot, (iii) HIV algorithmic
      directives in which confirmatory (Western blot) testing was not performed on a
      repeatedly reactive screen test. The outcome of this analysis identified
      opportunities for improvement, including implementation of a newly approved
      (automated) confirmatory assay and improved communication between the clinician
      and laboratory. CONCLUSIONS: HIV testing remains problematic despite significant
      advances in HIV test performance and algorithm development, presenting new and
      unexpected issues. Ensuring a high-quality management system including
      implementation of the latest HIV technologies and algorithms along with human
      resources and policies are required to minimize the impact of false positive
      diagnoses, especially in the era of universal screening and 'test and treat'
      recommendations.

PMID- 29031157
TI  - A European multi-centre External Quality Assessment (EQA) study on phenotypic and
      genotypic methods used for Herpes Simplex Virus (HSV) drug resistance testing.
AB  - BACKGROUND: Herpes Simplex Virus (HSV) drug resistance is a significant public
      health concern among immunocompromised individuals. Phenotypic assays are
      considered the gold standard method for detecting HSV drug resistance. However,
      plaque reduction assays (PRAs) are technically demanding, often with long
      turnaround times of up to four weeks. In contrast, genotypic tests can be
      performed within a few days. OBJECTIVES: The development and coordination of the
      first European External Quality Assessment (EQA) study to evaluate phenotypic and
      genotypic methods used for HSV drug resistance testing in specialised reference
      laboratories. STUDY DESIGN: Four HSV-1 or HSV-2 strains with different antiviral
      susceptibility profiles were isolated from clinical samples. Isolates were
      quantified by qPCR, and aliquoted in culture medium. One isolate was distributed
      at two dilutions to help assess assay sensitivity. The panel was distributed to
      five European centres with a six-week deadline for the return of phenotypic and
      genotypic results, together with clinical reports. RESULTS: Four out of five
      participating labs returned results by the deadline. Limited results were later
      available from the fifth lab. Phenotypic and genotypic data were largely, but not
      completely, concordant. An unusual resistance profile shown by one of the samples
      was explained by the detection of a mixed virus population after extensive
      further investigation by one of the centres. CONCLUSIONS: Discordant clinical
      outputs reflecting the diversity of phenotypic methodologies demonstrated the
      utility of this exercise. With emerging genotypic technologies looking to
      supplant phenotyping, there is a need for curated public databases, accessible
      interpretation tools and standardised control materials for quality management.
      By establishing a network of testing laboratories, we hope that this EQA scheme
      will facilitate ongoing progress in this area.

PMID- 29031158
TI  - A potential contribution to human identification using peri-mortem trauma: An
      example from Peru.
AB  - This is an exploratory study into the need for additional lines of forensic
      evidence in humanitarian cases using applied research. One hundred and twenty
      four, still unidentified terrorism inmates, were killed after surrendering to the
      Peruvian Army once it took control of the San Pedro-Lurigancho prison in Lima,
      Peru in 1986. Two questions are put forward: first, to what extent mechanism of
      injury (gunshot, blunt, sharp force) and bodily distribution of those injuries
      allow us to classify individuals into discrete sub-groups of people? The second
      question is to what respect can such a classification become an additional line
      of evidence assisting in generating hypotheses of identity regarding those
      individuals? The analysis of the 109 recovered bodies and their associated
      evidence show a sub group of four individuals differentiated from the rest based
      on the combination of injuries (gunshot and blunt force trauma), opposing
      trajectories and weapons. While the results do not constitute per se proof of
      identity, they suggest that such a small group of people could have been singled
      out from the crowd and treated differently. Such information constitutes an
      additional line of evidence to formulate hypotheses of identity for certain
      individuals that could have been ring leaders/cadres of the Shining Path, a
      Maoist movement that started the Internal Armed Conflict (1980-2000) in Peru.

PMID- 29031159
TI  - Development of fingermarks on Latex gloves: The solution to a challenging
      surface.
AB  - Used Latex gloves found at crime scenes can provide strong evidence against a
      suspect as they almost certainly contain both the fingermarks and DNA of the
      perpetrator who had worn them. However, over the years, Latex gloves have proved
      to be a rather difficult substrate for fingermarks development, with most of the
      standard techniques producing poor results. In this study, the two main protocols
      for development on either porous or non-porous surfaces: Ninhydrin-HFE and
      superglue fuming followed by crystal violet (CV) dyeing, respectively, had been
      examined on 100 disposable Latex gloves from twenty five donors. The results
      distinctly showed a high superiority of Ninhydrin-HFE over the superglue fuming
      indicating the porous rather than the non-porous properties of the interior of
      the gloves. Yet, not all the usual ninhydrin development formulations yielded the
      desirable results, leading to the conclusion that the success of development
      rests on the solvent-sensitive structure of the gloves. As natural latex contains
      contaminant proteins, that were found to cause allergic reactions in different
      people, the manufacturing of disposable gloves had been altered over the years to
      prevent contact with these proteins by adding an intrinsic polymer-coating. Thus,
      it was essential to use an inert solvent system that should keep the interior
      polymer-coating intact, allowing a reaction only with the amino acids on the
      surface rather than the latex proteins in the glove. The SEM analyses showed that
      HFE-7100 as opposed to petroleum ether, does not harm the inner coating, hence,
      providing the ideal solution to this challenging surface.

PMID- 29031160
TI  - Examining temporal alterations in Social Anxiety Disorder and Posttraumatic
      Stress Disorder: The relation between autobiographical memory, future goals, and
      current self-views.
AB  - The self is a multi-faceted and temporally dynamic construct reflecting
      representations and beliefs about identity in the past, present, and future.
      Clinical studies have shown that individuals with Posttraumatic Stress Disorder
      (PTSD) and Social Anxiety Disorder (SAD) exhibit alterations in self-related
      processing but these studies have focused primarily on memory. Few studies in
      PTSD and SAD have examined self-related processing for the present and future,
      and no studies have directly compared these processes across these two disorders.
      Individuals diagnosed with PTSD (n=21), SAD (n=21), and healthy controls (n=21)
      completed cognitive tasks related to the past, present, and future. Disorder
      congruent temporal alterations were found across both disorders. Further,
      regression analyses revealed that trauma-related memories were significantly
      predicted by future goals related to the trauma, whereas social anxiety-related
      recall was predicted by current socially anxious self-views. Thus, although self
      related processing may be common in PTSD and SAD, those aspects of the self most
      strongly associated with disorder-congruent recall differ by disorder. Self
      alterations may be modifiable and developing a better understanding of past,
      present, and future self-processing might aid in the development of interventions
      that target these process.

PMID- 29031161
TI  - Understanding the role of DNA polymerase lambda gene in different growth and
      developmental stages of Oryza sativa L. indica rice cultivars.
AB  - DNA polymerase lambda (Pol lambda) is the only member of DNA polymerase family X
      present in plants. The enzyme is ddNTP sensitive as it contains the conserved C
      terminal Pol beta domain. The 1.1 kb partial coding sequence isolated spanned the
      whole 3' regions of the gene containing functionally important domains of the Pol
      lambda gene. Comparative in silico studies from both indica and japonica
      cultivars involving homology modelling showed that the model for the partial Pol
      lambda gene was stable and acceptable. The alignment of both the protein models
      showed a RMS value of 0.783. Apart from this, expression of Pol lambda and its
      relative activity is studied during different development stages of three
      different indica rice cultivars (IR29, Nonabokra and N22). Enhanced accumulation
      and higher activity of Pol lambda during the early seedling stage was detected.
      Higher expression and activity were observed in the anthers, which was probably
      necessary for DNA repair during microspore formation. However, during the
      maturation stage of seed development and plant growth, expression and the
      activity of Pol lambda decreased due to slow metabolic activity and a reduced
      rate of cell division respectively. Furthermore, the expression and activity of
      Pol lambda were found to be higher in IR29 in comparison to Nonabokra and N22.
      IR29 is a rice cultivar susceptible to environmental stresses and hence it
      encounters higher DNA damages. The enhanced presence and activity of the Pol
      lambda enzyme in IR29 with respect to the other two cultivars, which are more
      tolerant to the environmental stresses during various developmental stages, is
      therefore explainable.

PMID- 29031162
TI  - DNA demethylation activates genes in seed maternal integument development in rice
      (Oryza sativa L.).
AB  - DNA methylation is an important epigenetic modification that regulates various
      plant developmental processes. Rice seed integument determines the seed size.
      However, the role of DNA methylation in its development remains largely unknown.
      Here, we report the first dynamic DNA methylomic profiling of rice maternal
      integument before and after pollination by using a whole-genome bisulfite deep
      sequencing approach. Analysis of DNA methylation patterns identified 4238
      differentially methylated regions underpin 4112 differentially methylated genes,
      including GW2, DEP1, RGB1 and numerous other regulators participated in maternal
      integument development. Bisulfite sanger sequencing and qRT-PCR of six
      differentially methylated genes revealed extensive occurrence of DNA
      hypomethylation triggered by double fertilization at IAP compared with IBP,
      suggesting that DNA demethylation might be a key mechanism to activate numerous
      maternal controlling genes. These results presented here not only greatly
      expanded the rice methylome dataset, but also shed novel insight into the
      regulatory roles of DNA methylation in rice seed maternal integument development.

PMID- 29031163
TI  - Ebola virus requires phosphatidylinositol (3,5) bisphosphate production for
      efficient viral entry.
AB  - For entry, Ebola virus (EBOV) requires the interaction of its viral glycoprotein
      with the cellular protein Niemann-Pick C1 (NPC1) which resides in late endosomes
      and lysosomes. How EBOV is trafficked and delivered to NPC1 and whether this is
      positively regulated during entry remain unclear. Here, we show that the PIKfyve
      ArPIKfyve-Sac3 cellular complex, which is involved in the metabolism of
      phosphatidylinositol (3,5) bisphosphate (PtdIns(3,5)P2), is critical for EBOV
      infection. Although the expression of all subunits of the complex was required
      for efficient entry, PIKfyve kinase activity was specifically critical for entry
      by all pathogenic filoviruses. Inhibition of PIKfyve prevented colocalization of
      EBOV with NPC1 and led to virus accumulation in intracellular vesicles with
      characteristics of early endosomes. Importantly, genetically-encoded
      phosphoinositide probes revealed an increase in PtdIns(3,5)P2-positive vesicles
      in cells during EBOV entry. Taken together, our studies suggest that EBOV
      requires PtdIns(3,5)P2 production in cells to promote efficient delivery to NPC1.

PMID- 29031164
TI  - Productive replication of avian influenza viruses in chicken endothelial cells is
      determined by hemagglutinin cleavability and is related to innate immune escape.
AB  - Endotheliotropism is a hallmark of gallinaceous poultry infections with highly
      pathogenic avian influenza (HPAI) viruses and a feature that distinguishes HPAI
      from low pathogenic avian influenza (LPAI) viruses. Here, we used chicken aortic
      endothelial cells (chAEC) as a novel in vitro infection model to assess the
      susceptibility, permissiveness, and host response of chicken endothelial cells
      (EC) to infections with avian influenza (AI) viruses. Our data show that
      productive replication of AI viruses in chAEC is critically determined by
      hemagglutinin cleavability, and is thus an exclusive trait of HPAI viruses.
      However, we provide evidence for a link between limited (i.e. trypsin-dependent)
      replication of certain LPAI viruses, and the viruses' ability to dampen the
      antiviral innate immune response in infected chAEC. Strikingly, this cell
      response pattern was also detected in HPAI virus-infected chAEC, suggesting that
      viral innate immune escape might be a prerequisite for robust AI virus
      replication in chicken EC.

PMID- 29031165
TI  - Characterization and morphological analysis of individual aerosol of PM10 in
      urban area of Lucknow, India.
AB  - Airborne particulate matters were collected during the period of October 2015 to
      September 2016 in Lucknow at different sampling sites. The annual mean
      concentration of particulate matter was found to be relatively higher than the
      limits prescribed by National ambient air quality standards (NAAQS), United State
      Environmental Protection Agency (USEPA) and World Health Organization (WHO).
      Particulate matters were studied for morphological analysis, elemental
      composition and functional group variability with the help of Scanning Electron
      Microscope-Energy Dispersive Spectroscopy (SEM-EDS) followed by Fourier Transform
      Infrared spectroscopy (FTIR). Morphological characteristics viz. particle count,
      aspect ratio, circulatory, roundness, equivalent spherical diameter (ESD) and
      surface area revealed that the particles were perfectly spherical to irregular in
      shape. Based on the morphology and elemental composition, four clusters of a
      particulates namely organic particle with inorganic inclusion, soot, tar balls
      and aluminosilicates were found. FTIR spectra revealed the presence of sulfate,
      bisulfate, particulate water, silicate, ammonium, aliphatic carbon, aliphatic
      alcohol, carbonyl and organic nitrates.

PMID- 29031166
TI  - Can the Perceived Barriers to Psychological Treatment Scale be used to
      investigate treatment barriers among females with disordered and non-disordered
      eating behaviours?
AB  - There is a lack of psychometrically sound instruments to assess treatment
      barriers among individuals with disordered eating behaviours. This study examined
      the factor structure and psychometric properties of the Perceived Barriers to
      Psychological Treatment scale (PBPT; Mohr et al., 2010) among a sample of
      individuals with disordered eating behaviours. Participants were 708 females aged
      14 years and older who completed an online survey. The sample was randomly
      divided in two for the conduct of exploratory (EFA) and confirmatory (CFA) factor
      analyses. EFA suggested a seven-factor structure retaining 24 of the original 27
      items (variance explained = 60%, alpha = 0.91). Factors were stigma,
      participation restrictions, negative evaluation of treatment, lack of motivation,
      emotional concerns, access restrictions, and time constraints. To assess clinical
      sensitivity, we conducted a secondary EFA utilising only clinical cases from this
      sample, which supported the solution but suggested retaining 25 of the original
      27 items (variance explained = 58%, alpha = 0.89). The 25-item, seven-factor
      solution was further supported by CFA with an independent sample. Construct
      validity was also supported. The study suggests that the instrument will provide
      clinicians and researchers with a valid and reliable method of assessing
      treatment barriers in disordered eating samples.

PMID- 29031167
TI  - Impaired central coherence in patients with anorexia nervosa.
AB  - The purpose of this study was to investigate the characteristics of central
      coherence in patients with anorexia nervosa (AN). 22 female patients with AN
      (median age = 31.50 (QD = 8.13) years) and 33 female healthy controls (HC)
      (median age = 28.00 (QD = 8.50) years) participated in the study. Their central
      coherence was assessed with the Rey Complex Figure Task (RCFT). Clinical symptoms
      were evaluated with the Beck Depression Inventory-II and the State-Trait Anxiety
      Inventory-Form JYZ. The results showed that AN patients' Central Coherence Index
      and accuracy scores in copy, 3-min delayed recall and 30-min delayed recall tasks
      of the RCFT were significantly lower than those of HC. Moreover, the significant
      differences in Central Coherence Index score in copy task and accuracy scores in
      3-min delayed recall and 30-min delayed recall tasks remained when the effects of
      depression, anxiety and starvation were eliminated statistically. These findings
      may explain some characteristics of AN patients such as focusing on local rather
      than global picture in their perception of body or life.

PMID- 29031168
TI  - Effect of microstructural elongation on backscattered field: Intensity
      measurement and multiple scattering estimation with a linear transducer array.
AB  - The effect of microstructural elongation on ultrasonic backscattered fields was
      studied. Two methods for determining the elongation direction of macrozones in
      titanium alloys, using the anisotropic spatial coherence of the backscattered
      field, are presented. Both methods use a phased array attached on a rotative
      holder that records the array response matrix at several angles. Two titanium
      alloys were investigated: TA6V and Ti17. TA6V exhibited a strong macrozone
      elongation, whereas Ti17 macrozones were found equiaxial. The first method is
      based on the measurement of backscattered intensity in function of the probe
      angle relative to the macrozones elongation direction. An angular dependence of
      backscattered intensity is observed in presence of elongated scatterers, and
      their elongation direction is collinear with the probe direction corresponding to
      a minimal intensity. This variability is linked to both piezoelectric shape and
      the backscattered field spatial properties. The second method is based on the
      measurement of the relative proportion of single to multiple scattering in a
      diffusive media, using a simplified version of the single scattering filter
      developed in Aubry and Derode (2009). It allows the measurement of the level of
      multiple scattering: both titanium alloys exhibited strong multiple scattering.
      The elongation direction was determined as the direction of minimal multiple
      scattering. Furthermore, these results were confirmed by the measurement of the
      coherent backscattering cone on both samples.

PMID- 29031169
TI  - 3,4-Dimethoxybenzohydrazide derivatives as antiulcer: Molecular modeling and
      density functional studies.
AB  - 3,4-Dimethoxybenzohydrazide derivatives (1-25) have been synthesized and
      evaluated for their urease inhibitory potential. Among the series, compounds 2,
      3, 4 and 5 with IC50 values 12.61 +/- 0.07, 18.24 +/- 0.14, 19.22 +/- 0.21, and
      8.40 +/- 0.05 uM, respectively, showed excellent urease inhibitory potentials
      when compared with standard thiourea (IC50 value 21.40 +/- 0.21 uM). Compounds 1,
      6, 8, 18, 19 and 20 also showed good to moderate inhibition, while the remaining
      compounds were found to be completely inactive. The structures of compounds 6 and
      25 were confirmed through X-ray crystallography while the structures of remaining
      compounds were confirmed through ESI-MS and 1H NMR. Molecular docking studies
      were performed understand the binding interactions with enzyme active site. The
      synthesized compounds were evaluated for cytotoxicity and found to be nontoxic.

PMID- 29031170
TI  - A dose-escalation study of bi-daily once weekly oral docetaxel either as
      ModraDoc001 or ModraDoc006 combined with ritonavir.
AB  - INTRODUCTION: Two solid dispersions of docetaxel (denoted ModraDoc001 capsule and
      ModraDoc006 tablet (both 10 mg)) were co-administered with 100 mg ritonavir (/r)
      and investigated in a bi-daily once weekly (BIDW) schedule. Safety, maximum
      tolerated dose (MTD), pharmacokinetics (PK) and preliminary activity were
      explored. METHODS: Adult patients with metastatic solid tumours were included in
      two dose-escalation arms. PK sampling was performed during the first week and the
      second or third week. Safety was evaluated using US National Cancer Institute's
      Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0.
      Antitumour activity was assessed every 6 weeks according to Response Evaluation
      Criteria in Solid Tumours (RECIST) version 1.0. RESULTS: ModraDoc001 capsule/r
      and ModraDoc006 tablet/r were administered to 17 and 28 patients, respectively.
      The most common adverse events were nausea, vomiting, diarrhoea and fatigue,
      mostly of grade 1-2 severity. Grade 3/4 neutropenia/neutropenic fever was
      observed in 2 patients (4%). The MTD was determined as 20/20 mg ModraDoc001/r and
      30/20 mg ModraDoc006/r (morning/afternoon dose) once weekly. The mean area under
      the plasma concentration-time curve (AUC0-48) +/- standard deviation at the MTD
      for ModraDoc001/r and ModraDoc006/r were 686 +/- 388 ng/ml*h and 1126 +/- 382
      ng/ml*h, respectively. Five partial responses were reported as best response to
      treatment. CONCLUSION: Oral administration of BIDW ModraDoc001/r or ModraDoc006/r
      is feasible. The once weekly 30/20 mg ModraDoc006 tablet/r dose-level was
      selected for future clinical development. Antitumour activity is promising.

PMID- 29031171
TI  - Transverse testicular ectopia with inguinal hernia - A rare case report.
AB  - INTRODUCTION: Transverse aberrant testicular maldescent is an extremely rare
      congenital anomaly characterized by the migration of one testicle towards the
      opposite inguinal canal. Mostly such cases are reported in children and they are
      very rarely seen in adults. PRESENTATION OF CASE: We report a case of a 24year
      old male patient with left reducible indirect inguinal hernia with absence of
      testis in the right hemiscrotum.On surgical exploration, the patient had both the
      testicles on the left side. Left meshplasty with left orchidectomy for the
      atrophic ectopic testis was done. DISCUSSION: It can either be associated with
      inguinal hernia, persistent Mullerian duct structures, hypospadias, true or
      pseudo hermaphroditism or other scrotal abnormalities. Usually treatment includes
      transeptal orchiopexy or extra peritoneal transposition of the testis.
      CONCLUSION: This rare anomaly is usually diagnosed incidentally during surgical
      exploration and carries importance due to risk of malignant transformation of the
      ectopic testis. Therefore it needs specific long term follow up after orchiopexy.

PMID- 29031172
TI  - A parapharyngeal space schwannoma arising from the vagus nerve: A case report.
AB  - INTRODUCTION: Tumours of the parapharyngeal space are rare. Only 0.5% of head and
      neck tumours occur in this space. Surgical excision of parapharyngeal space
      lesions is challenging because of the anatomical complexity of the area.
      PRESENTATION OF CASE: A 31-year-old male patient was referred by his general
      dental practitioner for removal of lower wisdom teeth due to multiple episodes of
      pericoronitis. At the initial examination, an incidental finding was made of a
      large fluctuant posterior oropharyngeal swelling. A fluid aspirate was taken from
      the lesion but this was inconclusive. The patient underwent an urgent MRI and CT
      neck revealing a large parapharyngeal mass. An incisional biopsy of the lesion
      confirmed the presence of a vagal nerve schwannoma which was subsequently removed
      via a transcervical approach. DISCUSSION: Due to their slow growing and painless
      nature, they are often not detected until they are large enough to palpate or
      visualise. It may cause secondary symptoms such as dysphagia, hoarseness and
      nasal obstruction. This case represents a typical presentation of a
      parapharyngeal schwannoma and reiterates the subtle and often ambiguous nature of
      the lesion. CONCLUSION: Vagal schwannomas in the parapharyngeal space are rare.
      They usually present in the form of an isolated intraoral or neck mass. A
      positive diagnosis is made on imaging and confirmed by histopathological
      examination. Complete surgical excision is the treatment of choice and recurrence
      rates are low.

PMID- 29031173
TI  - An unusual case of transpelvic impalement injury: A case-report.
AB  - INTRODUCTION: Impalement injury is a rare type of mechanical injury following
      forceful insertion of projecting object into the body. Careful planning for
      removal of the impaling object is essential to decrease the blood loss and
      preserve the function of the injured organ. PRESENTATION OF CASE: A 27 year-old
      male fell from 4m height over a U shaped projecting up metallic bar. The bar
      penetrated the left side of the pelvis and traversed through the left iliac bone
      causing a comminuted fracture in the supra-acetabular region extending to the
      left psoas muscle, injuring the viscera and causing fracture of the right femur.
      Exploratory laparotomy was performed and the metallic bar was pulled out from the
      sigmoid colon through the inlet of the injury. Intramedullary nailing was
      performed for femur fracture. The patient developed infection (Methicillin
      sensitive Staphylococcus aureus and Escherichia coli) during the post-operative
      course that was successfully managed with antibiotic therapy. Finally the patient
      was sent home after a week in a good health condition. DISCUSSION: Two surgical
      teams worked in sequence to fix the injuries starting with the trauma team
      followed by the orthopedic surgeons. CONCLUSION: Impalement injury is a serious
      injury that needs a multidisciplinary team with a coordinated approach to achieve
      a favorable outcome.

PMID- 29031174
TI  - Dynamic right ventricular outflow obstruction: A rare cause of hypotension during
      anestesia induction.
AB  - INTRODUCTION: Dynamic obstruction of right ventricle outflow tract (RVOTO) is a
      rare condition that may acutely cause severe heart failure. It has been reported
      in some hypertrophic cardiomyopathies, after lung transplantation, and in some
      cases of hemodynamic instability after cardiopulmonary bypass. PRESENTATION OF
      CASE: We report the case of a 71-year-old man who developed severe hypotension
      during the induction of general anesthesia for surgical coronary
      revascularization. Hypotension did not respond to the initial treatment with
      vasoconstrictors and fluids. RVOTO was suspected during pulmonary artery
      catheterization because of the difficulty of the catheter tip to move from the
      right ventricle to the pulmonary artery and, successively, because of the finding
      of a large gradient between the systolic pressure in the right ventricle and in
      the pulmonary artery. The diagnosis was confirmed by transesophageal
      echocardiogram (TEE). Hemodynamics recovered after the infusion of cristalloids,
      1L, and the suspension of vasoconstrictors and inotropes. DISCUSSION: This is the
      first case in which RVOTO was observed during the induction of general
      anesthesia. Although this is a rare condition, the diagnostic suspect is of
      outmost importance because treatment is mainly based on fluid administration, and
      drugs with positive inotropic properties (like most vasoconstrictors) are
      contraindicated. CONCLUSIONS: RVOTO is an unusual, but possible cause of severe
      arterial hypotension during general anesthesia induction. TEE is useful for the
      evaluation of severely hypotensive patients who do not respond to routine
      treatment with fluids and vasoconstrictors.

PMID- 29031175
TI  - Parasitic leiomyoma: A case report with literature review.
AB  - INTRODUCTION: Parasitic leiomyoma is an extremely rare variant of uterine
      leiomyoma occurring outside uterus. The aim of this study is to report a case of
      parasitic leiomyoma with brief literature report. CASE REPORT: A 46-yearo-old
      lady presented with upper abdominal heaviness and swelling of about 6year
      duration. associated with nausea, shortness of breath and palpitation. There was
      large well defined, mobile, hard mass in epigastric area measuring about 12*10cm.
      Abdominal ultrasound showed well defined, solid, 94*76mm, mass in the epigastric
      region. Abdominal computed tomography scan showed round homogenous opacity at the
      epigastric region with features consistent with benign lesion. Laparotomy was
      done, histopathological examination confirmed the diagnosis of parasitic
      leiomyoma. CONCLUSION: Parasitic leiomyoma is an extremely rare subtype of
      uterine leiomyoma, presents with vague symptoms, diagnosed by ultrasound and
      managed by complete resection. Previous uterine procedures have been implicated
      in its etiology.

PMID- 29031176
TI  - A case of dedifferentiated liposarcoma of the heart and stomach.
AB  - INTRODUCTION: Liposarcoma of the heart and stomach is rare. PRESENTAION OF CASE:
      We report a case of liposarcoma in both organs with dedifferentiated histology. A
      patient was referred to our hospital with anorexia and weight loss. Upper
      gastrointestinal tract endoscopy revealed 5-10-mm elevated lesions, and
      echocardiography and computed tomography showed tumorous lesions in the left
      atrium. Tumor resection and mitral valve replacement were performed, and biopsy
      was performed for the gastric tumor. Both the tumors were diagnosed as
      dedifferentiated liposarcoma. DISCUSSION: Liposarcoma - a mesenchymal malignant
      tumor that contains lipoblasts - is the second most common soft tissue sarcoma.
      The tumor occurs most frequently in the limbs and retroperitoneum and rarely
      originates in the heart and the stomach. CONCLUSION: Chemotherapy and
      radiotherapy are only adjunctive therapies but not es as standard treatment for
      cardiac tumors. Therefore, we believe that wide surgical resection was the best
      choice of treatment in the present case.

PMID- 29031177
TI  - Giant gastric lipoma presenting as GI bleed: Enucleation or Resection?
AB  - INTRODUCTION: Gastric lipomas are unusual benign lesions and account for less
      than 1% of all tumours of the stomach and 5% of all gastrointestinal lipomas
      (Thompson et al.2003; Fernandez et al. 1983 [1,2]). Although predominantly
      asymptomatic and indolent; they may present with gastric outlet obstruction and
      upper gastrointestinal (GI) bleeding owing to size and ulceration. Only a few
      cases have been reported, presenting large in size with massive GI bleeding
      (Alcalde Escribano et al. 1989; Johnson et al. 1981 [3,4]). PRESENTATION OF CASE:
      We report the case of a 62-year-old gentleman who presented to the emergency
      department with massive upper GI hemorrhage. He was initially resuscitated and
      stabilized. Later gastroscopy showed a large submucosal tumour (Fig. 1). Biopsy
      revealed adipose tissue. Computed tomography (CT) scan of the abdomen and pelvis
      showed a huge well defined oval soft tissue lesion measuring about 16*8*8cm. The
      mass noted a homogenous fat density arising from the posterior wall of stomach
      with no extramural infiltration (Fig. 2). The tumour was completely enucleated
      through an explorative gastrotomy incision (Fig. 4). DISCUSSION AND CONCLUSION:
      Massive bleeding secondary to a giant gastric lipoma is a rare finding of a rare
      disease. The majority of cases in the literature result in major gastric
      resection. Familiarity with its radiological findings and a high index of
      suspicion can lead to proper diagnosis in the acute setting. If malignancy is
      carefully ruled out, stomach preserving surgery is an optimal treatment option.

PMID- 29031178
TI  - Undifferentiated pleomorphic sarcoma of the neck - A case report.
AB  - Undifferentiated pleomorphic sarcoma very rarely affect the neck. We report a
      case of a 62year old man who presented with a right sided skin lump which he
      noticed after sustaining a neck contusion in a road traffic accident about one
      year ago. The initial CT and ultrasound scans of the lump were suggestive of a
      thrombosed varix. Clinical examination showed a hard skin nodule with signs of
      tethering. He underwent a wide excision of the skin nodule and the histology
      showed undifferentiated pleomorphic sarcoma with margins involved. He
      subsequently underwent another re-excision of margins and pectoralis major flap
      reconstruction. Following surgery, he was also prescribed adjuvant radiotherapy
      and he remains well about 12 months after follow up. The surgical management of
      undifferentiated pleomorphic sarcoma in the neck is challenging due to the
      proximity of critical neck structures and the need to obtain clear margins. Thus,
      adjuvant radiotherapy is often used to improve disease control.

PMID- 29031179
TI  - Carbosilane metallodendrimers based on copper (II) complexes: Synthesis, EPR
      characterization and anticancer activity.
AB  - A series of new organometallic carbosilane dendrimers functionalized with
      Copper(II) complex on the surface were synthesized and characterized as potential
      anticancer agents. These metallodendrimers were synthesized through the reaction
      of dendritic ligands containing N,N- and N,O- donor atoms able to act as
      chelating agents with CuCl2 as metallic ion precursor. The structural
      characterization of these complexes was addressed through the use of different
      analytical and spectroscopical techniques. Particularly, an electron paramagnetic
      resonance study was performed to corroborate the coordination properties of these
      dendritic ligands. A preliminary study was carried out to establish the
      cytotoxicity of the new synthesized compounds in human prostate (PC3) and human
      cervical (HeLa) cancer cell lines in order to evaluate their potential as
      anticancer agents and compare their activity with other copper or analogous
      ruthenium metallodendrimers.

PMID- 29031180
TI  - Design of silk proteins with increased heme binding capacity and fabrication of
      silk-heme materials.
AB  - In our previous studies, heme was bound into honeybee silk to generate materials
      that could function as nitric oxide sensors or as recoverable heterogeneous
      biocatalysts. In this study, we sought to increase the heme-binding capacity of
      the silk protein by firstly redesigning the heme binding site to contain
      histidine as the coordinating residue and secondly, by adding multiple histidine
      residues within the core of the coiled coil core region of the modified silk
      protein. We used detergent and a protein denaturant to confirm the importance of
      the helical structure of the silk for heme coordination. Aqueous methanol
      treatment, which was used to stabilize the materials, transformed the low-spin,
      six-coordinate heme to a five-coordinate high-spin complex, thus providing a
      vacant site for ligand binding. The optimal aqueous methanol treatment time that
      simultaneously maintains the helical protein structure and stabilizes the silk
      material without substantial leaching of heme from the system was determined.

PMID- 29031181
TI  - MdHY5 positively regulates cold tolerance via CBF-dependent and CBF-independent
      pathways in apple.
AB  - Cold stress is a major external stimulator that affects crop quality and
      productivity. The CBF cold regulatory pathway has been regarded as a master
      regulator in the response to cold stress. In this study, we found that the apple
      bZIP transcription factor, MdHY5, was responsive to cold treatment both at the
      transcriptional and at the post-translational levels. Moreover, overexpression of
      MdHY5 enhanced cold tolerance in apple calli and Arabidopsis. Subsequently, EMSA
      assay and transient expression assay demonstrated that MdHY5 positively regulated
      the transcript of MdCBF1 by binding to G-Box motif of its promoter. Furthermore,
      MdHY5 also regulated the expression of CBF-independent cold-regulated genes.
      Taken together, our data suggest that MdHY5 positively modulates plant cold
      tolerance through CBF-dependent and CBF-independent pathways, providing a deeper
      understanding of MdHY5-regulated cold tolerance in apple.

PMID- 29031182
TI  - Translating the HAM-D into the MADRS and vice versa with equipercentile linking.
AB  - BACKGROUND: The Hamilton Depression Rating Scale (HAM-D) and the Montgomery
      Asberg Depression Rating Scale (MADRS) are scales used frequently to rate the
      symptoms of depression. There are many situations in which it is important to
      know what a given total score or a percent reduction from baseline score of one
      scale means in relation to the other scale. METHOD: We used the equipercentile
      linking method to identify corresponding scores of simultaneous HAM-D and MADRS
      ratings in 4388 patients from 31 mirtazapine trials in major depressive disorder.
      Data were collected at baseline and at weeks 1, 2 and 4. RESULTS: HAM-D scores of
      10, 20, 30 and 40 roughly corresponded to MADRS scores of 13, 26, 39 and 52-53,
      respectively. An absolute HAM-D improvement of 10, 20, 25 points corresponded to
      a MADRS improvement of 12, 26, and 34. A percentage improvement from baseline of
      the HAM-D was approximately the same as a percentage improvement on the MADRS.
      CONCLUSION: These results are important for the comparison of trials that used
      the HAM-D and MADRS. We present conversion tables for future research.

PMID- 29031183
TI  - Childhood hunger and depressive symptoms in adulthood: Findings from a population
      based study.
AB  - BACKGROUND: Several studies have linked childhood hunger to an increased risk for
      later depression. However, as yet, there has been little research on this
      relation in adults of all ages or whether there are sex differences in this
      association. The current study examined these issues using data from a national
      population-based sample. METHODS: Data were analyzed from 5095 adults aged 25-84
      collected during the Estonian Health Interview Survey 2006. Information was
      obtained on the frequency of going to bed hungry in childhood and on depressive
      symptoms using the Emotional State Questionnaire (EST-Q). Logistic regression
      analysis was used to examine the association between hunger and depression while
      controlling for other demographic, socioeconomic and health-related variables.
      RESULTS: In a fully adjusted model, going to bed hungry in childhood either
      sometimes or often was associated with significantly increased odds for
      depressive symptoms. When the analysis was stratified by sex the association was
      more evident in men where any frequency of childhood hunger was linked to adult
      depression while only women who had experienced hunger often had higher odds for
      depressive symptoms in the final model. LIMITATIONS: Data on childhood hunger
      were retrospectively reported and may have been affected by recall bias. We also
      lacked information on potentially relevant variables such as other childhood
      adversities that might have been important for the observed associations.
      CONCLUSION: Childhood hunger is associated with an increased risk for depressive
      symptoms among adults. Preventing hunger in childhood may be important for mental
      health across the life course.

PMID- 29031184
TI  - Gene-environment interactions between stress and 5-HTTLPR in depression: A meta
      analytic update.
AB  - BACKGROUND: Meta-analyses have yielded contradictory findings concerning the role
      of 5-HTTLPR in interaction with stress (GxE) in depression. The current meta
      analysis investigates if these contradictory findings are a result of differences
      between studies in methodological approaches towards the assessment of stress and
      depression. METHODS: After performing a systematic database search (February to
      December 2016), first, a meta-analysis was used to investigate the total effect
      size and publication bias. Second, stratified meta-analyses were used to
      investigate the potential moderating influence of different methodological
      approaches on heterogeneity of study findings. Third, a meta-regression was used
      to investigate the combined influence of the methodological approaches on the
      overall effect size. RESULTS: Results showed a small but significant effect of 5
      HTTLPR in interaction with stress in the prediction of depression (OR[95%CI] =
      1.18[1.09; 1.28], n = 48 effect sizes from 51 studies, totaling 51,449
      participants). There was no evidence of publication bias. Heterogeneity of effect
      sizes was a result of outliers and not due to different methodological approaches
      towards the assessment of stress and depression. Yet, there was some evidence
      that studies adopting a categorical and interview approach to the assessment of
      stress report higher GxE effects, but further replication of this finding is
      needed. LIMITATIONS: A large amount of heterogeneity (i.e., 46%) was not
      explained by the methodological factors included in the study and there was a low
      response rate of invited studies. CONCLUSIONS: The current meta-analysis provides
      new evidence for the robustness of the interaction between stress and 5-HTTLPR in
      depression.

PMID- 29031185
TI  - Diet quality and depression risk: A systematic review and dose-response meta
      analysis of prospective studies.
AB  - BACKGROUND: It has been claimed that the quality of a diet is associated with the
      incidence of depressive disorders. We sought to investigate the evidence for this
      claim. METHODS: Systematic searches were performed up to March 6th, 2017 in order
      to identify prospective cohort studies that reported on exposure to dietary
      patterns or food groups and the incidence of depression/depressive symptoms. Data
      from 24 independent cohorts (totalling 1,959,217 person-years) were pooled in
      random-effects meta-analyses. RESULTS: Adherence to a high-quality diet,
      regardless of type (i.e., healthy/prudent or Mediterranean), was associated with
      a lower risk of depressive symptoms over time (odds ratios ranged 0.64-0.78 in a
      linear dose-response fashion [P < 0.01]). A relatively low dietary inflammatory
      index was also associated with a somewhat lower incidence of depressive symptom
      (odds ratio = 0.81), although not in a dose-response fashion. Similar
      associations were found for the consumption of fish and vegetables (odds ratios
      0.86 and 0.82 respectively) but not for other high quality food groups (e.g.,
      fruit). Studies that controlled for depression severity at baseline or that used
      a formal diagnosis as outcome did not yield statistically significant findings.
      Adherence to low quality diets and food groups was not associated with higher
      depression incidence. LIMITATIONS: Our ability to detect confounders was only
      limited. CONCLUSION: There is evidence that a higher quality of a diet is
      associated with a lower risk for the onset of depressive symptoms, but not all
      available results are consistent with the hypothesis that diet influences
      depression risk. Prospective studies that control for relevant confounders such
      as obesity incidence and randomized controlled prevention trials are needed to
      increase the validity of findings in this field.

PMID- 29031186
TI  - Family functioning as perceived by parents and young offspring at high and low
      risk for depression.
AB  - BACKGROUND: Family dysfunction has been proposed as one of the environmental
      mechanisms whereby risk of depression is transmitted from mothers to their
      children. Using our sample of offspring at high and low familial risk for
      depression, we hypothesized that: a) high-risk offspring (n = 79) and their
      mothers will report more extensive family dysfunction than low-risk offspring (n
      = 82) and their mothers, b) family dysfunction will predict the extent of
      offspring's depressive symptoms, and c) family dysfunction will mediate the
      impact of mother's depression on offspring's depressive symptoms. METHODS: The
      study enrolled 161 offspring of parents who, in a previous study, were
      ascertained to have either childhood onset mood disorder or no history of a major
      psychiatric disorder. Parents completed questionnaires and a clinical interview
      about themselves, their offspring, and the family, while offspring also completed
      questionnaires about themselves and the family. RESULTS: We found support for all
      three hypotheses. The significant indirect effect between maternal depression and
      offspring depressive symptoms was driven primarily by offspring's, but not
      mothers', reports of family dysfunction. LIMITATIONS: Although our assessment of
      mother's early history of depression was done in a previous study, it is
      important to note that our results do not inform about causality because of the
      present study's cross-sectional nature. CONCLUSIONS: The results highlight the
      importance of detecting and treating family dysfunction, particularly via
      offspring report, as one way to lower the risk of depression transmission from
      mothers to their children.

PMID- 29031187
TI  - Modelling transitions in urban water systems.
AB  - Long term planning of urban water infrastructure requires acknowledgement that
      transitions in the water system are driven by changes in the urban environment,
      as well as societal dynamics. Inherent to the complexity of these underlying
      processes is that the dynamics of a system's evolution cannot be explained by
      linear cause-effect relationships and cannot be predicted under narrow sets of
      assumptions. Planning therefore needs to consider the functional behaviour and
      performance of integrated flexible infrastructure systems under a wide range of
      future conditions. This paper presents the first step towards a new generation of
      integrated planning tools that take such an exploratory planning approach. The
      spatially explicit model, denoted DAnCE4Water, integrates urban development
      patterns, water infrastructure changes and the dynamics of socio-institutional
      changes. While the individual components of the DAnCE4Water model (i.e. modules
      for simulation of urban development, societal dynamics and evolution/performance
      of water infrastructure) have been developed elsewhere, this paper presents their
      integration into a single model. We explain the modelling framework of
      DAnCE4Water, its potential utility and its software implementation. The
      integrated model is validated for the case study of an urban catchment located in
      Melbourne, Australia.

PMID- 29031188
TI  - Azithromycin sorption and biodegradation in a simulated California river system.
AB  - Azithromycin (AZ) is a widely-used macrolide antibiotic that is continually
      deposited into natural waterways by sewage effluent. Though recognized as an
      emerging contaminant of concern, little is known about its fate and transport in
      aquatic systems. American River soils and water were used to determine
      degradation of AZ in microcosms simulating flooded (anaerobic) and non-flooded
      (aerobic) California watershed conditions. Under aerobic conditions the
      degradation rate constant (k=0.0084 +/- 0.0039 day-1) and DT50 (82.52 +/- 56.54
      days) were calculated, as AZ disappearance indicated potential degradation.
      However, based on concurrent product appearance, less than one percent of the
      parent degraded over 150 days. Throughout the experiment microbial growth was
      observed by culturing in tryptic soy broth despite antibiotic addition and soil
      being autoclaved. Sorption likely contributes to AZ recalcitrance, thus the soil
      water partition coefficient (log Kd = 2.18 Lkg-1), Freundlich sorption and
      desorption coefficients (log Kf = 1.90 +/- 0.14 and log Kfd = 2.51 +/- 0.30,
      respectively), and organic-carbon-normalized distribution coefficient (log Koc =
      4.25 Lkg-1) were also calculated. Based on these results, AZ degradation in
      aquatic systems will likely be very limited and transport will fluctuate based on
      the extent of soil-water saturation or bulk movement of sediment.

PMID- 29031190
TI  - Basic actions to reduce dropout rates in distance learning.
AB  - Today's society, which is strongly based on knowledge and interaction with
      information, has a key component in technological innovation, a fundamental tool
      for the development of the current teaching methodologies. Nowadays, there are a
      lot of online resources, such as MOOCs (Massive Open Online Courses) and distance
      learning courses. One aspect that is common to all of these is a high dropout
      rate: about 90% in MOOCs and 50% in the courses of the Spanish National Distance
      Education University, among other examples. In this paper, we analyze a number of
      actions undertaken in the Master's Degree in Computational Mathematics at
      Universitat Jaume I in Castellon, Spain. These actions seem to help decrease the
      dropout rate in distance learning; the available data confirm their
      effectiveness.

PMID- 29031189
TI  - Renal Subcapsular xenografing of human fetal external genital tissue - A new
      model for investigating urethral development.
AB  - In this paper, we introduce our novel renal subcapsular xenograft model for the
      study of human penile urethral and clitoral development. We grafted fifteen
      intact fetal penes and clitorides 8-11 weeks fetal age under the renal capsules
      of gonadectomized athymic mice. The mice were treated with a subcutaneous pellet
      of dihydrotestosterone (DHT), diethylstilbestrol (DES) or untreated with
      hormones. Xenografts were harvested after fourteen days of growth and analyzed
      via serial histologic sectioning and immunostaining for Ki-67, cytokeratins 6, 7
      and 10, uroplakin and the androgen receptor. Non-grafted specimens of similar
      fetal age were sectioned and immunostained for the same antigenic markers. 14/15
      (93.3%) grafts were successfully propagated and harvested. The developing
      urethral plate, urethral groove, tubular urethra, corporal bodies and preputial
      lamina were easily identifiable. These structures demonstrated robust
      cellularity, appropriate architecture and abundant Ki-67 expression. Expression
      patterns of cytokeratins 6, 7 and 10, uroplakin and the androgen receptor in
      xenografted specimens demonstrated characteristic male/female differences
      analogous to non-grafted specimens. DHT treatment reliably produced
      tubularization of nascent urethral and vestibular structures and male patterns of
      androgen receptor expression in grafts of both genetic sexes while estrogenic or
      hormonally absent conditions reliably resulted in a persistent open
      urethral/vestibular groove and female patterns of androgen receptor expression.
      This model's success enables further study into causal pathways by which
      endocrine-disrupting and endocrine-mimicking substances may directly cause
      disruption of normal human urethral development or hypospadias.

PMID- 29031191
TI  - The effectiveness of a head-heart-hands model for natural and environmental
      science learning in urban schools.
AB  - We describe an environmental and natural science program called Nurture thru
      Nature (NtN) that seeks to improve mathematics and science performance of
      students in disadvantaged communities, and to increase student interest in
      Science, Technology, Engineering and Mathematics (STEM) careers. The program
      draws conceptual guidance from the Head-Heart-Hands model that informs the
      current educational movement to foster environmental understanding and
      sustainability. Employing an experimental design and data from seven cohorts of
      students, we find some promising, albeit preliminary, indications that the
      program can increase students' science knowledge and grades in mathematics,
      science and language arts. We discuss the special adaptations that environmental
      and sustainability education programs need to incorporate if they are to be
      successful in today's resource depleted urban schools.

PMID- 29031192
TI  - Growth and endocrine function in children with Dravet syndrome.
AB  - PURPOSE: Dravet syndrome is an intractable childhood epilepsy syndrome most often
      associated with an SCN1A mutation. In our clinical practice, several patients
      with Dravet syndrome were noted to have short stature and endocrine dysfunction.
      This has not been reported in the literature. Our study aim was to describe
      growth measurements and endocrine abnormalities in children with Dravet syndrome.
      METHOD: A retrospective chart review was performed at a single institution.
      Eligibility criteria included clinical and genetic (SCN1A) diagnosis of Dravet
      syndrome. Records were reviewed for height and weight measurements and serologic
      evidence of endocrine abnormality, as well as patient demographics, anti-seizure
      medication, and family history. Age and gender specific trend of height and
      weight measurements, using z-scores, were compared to CDC growth curves (Centers
      for Disease Control and Prevention [1]). RESULTS: Sixty-eight children were
      identified, 46% male, age 1-21 years, taking an average of 2.9 anti-seizure
      medications per patient. Mean growth parameter measurements were significant for
      decrease in height z-score of 0.10 (p=<0.001) and decrease in weight z-score of
      0.09 (p=<0.01) for every year increase in age, such that with increasing age the
      cohort moved farther away from the mean. The average group height and weight z
      score, at age 8, was -0.45 and -0.09, respectively. After adjusting for age,
      neither gender, family history, or anti-seizure medication was associated with
      height or weight z-score. Serologic endocrine results were available for 26
      children (38%). This identified low insulin-like growth factor 1 (IGF-1) in 7/15
      and low testosterone in 2/10. Two children received growth hormone
      supplementation. TSH testing was abnormal <10% of the time. CONCLUSIONS:
      Comorbidities in children with Dravet syndrome may involve more systems than
      previously reported. We report a cohort of children with Dravet syndrome with
      reduced height and weight growth trend, as well as a subset with endocrine
      dysfunction evidenced by low IGF-1 and testosterone levels. Additional
      prospective research is needed to further define the significance of this
      relationship.

PMID- 29031193
TI  - The retention of lacosamide in patients with epilepsy and intellectual disability
      in three specialised institutions.
AB  - PURPOSE: We describe the effectiveness of lacosamide as adjunctive therapy in
      patients with epilepsy and an intellectual disability. This information is
      relevant, as few data exist pertaining to this population with a high prevalence
      of (intractable) epilepsy. METHODS: We performed a retrospective study in three
      specialised institutions. Inclusion criteria were (1) focal onset or symptomatic
      generalized (2) therapy-resistant epilepsy, (3) intellectual disability and (4)
      residence in a care-facility for people with intellectual disabilities (PWID).
      The primary outcome variables were the retention rates of lacosamide, estimated
      through Kaplan-Meier survival analysis. Secondary outcomes were reported seizure
      control, side effects and clinical factors influencing discontinuation. RESULTS:
      One hundred and thirty-two patients were included. The median retention time of
      lacosamide in our cohort was four years. The estimated one-, two- and three-year
      retention rates of lacosamide were 64%, 57% and 56% respectively. Severity of
      intellectual disability and seizure type did not influence whether lacosamide was
      continued. In 48.5% of patients, a reduction of seizure activity was reported.
      Side effects were at least part of the reason for discontinuing treatment in
      26.5% of all patients. Common side effects were tiredness/somnolence (in 30.3%),
      aggression/agitation (24.2%), and instable gait (15.2%). Five deaths during
      follow-up were considered unlikely to be related to the use of lacosamide. One
      patient died unexpectedly within two months of treatment onset, probably this was
      a case of SUDEP. CONCLUSION: These retention rates of lacosamide in PWID are
      similar to rates of previously registered anti-epileptic drugs in PWID.
      Behavioural side effects were noted in a high proportion compared to the general
      literature on lacosamide. Other side effects were in line with this literature.
      Lacosamide seems effective and safe for PWID and refractory epilepsy.

PMID- 29031194
TI  - The prevalence and characteristics of epilepsy in patients with multiple
      sclerosis in Nordland county, Norway.
AB  - PURPOSE: The prevalence of epilepsy among patients with multiple sclerosis (MS)
      has been found higher than in the general population. Although cortical pathology
      may be involved, the causal link between MS and epileptic seizures is still
      unclear. We aimed to identify and describe the patients with active epilepsy in a
      previously described population based MS-cohort. METHODS: Medical records of all
      patients with MS in Nordland County on January 1, 2010, were scrutinizing for
      evidence of comorbid seizures and epilepsy. RESULTS: Among 431 patients with MS,
      we identified 19 (4.4%) with a history of seizures or epilepsy. Fourteen (3.2%)
      of these had active epilepsy defined as use of antiepileptic drugs or seizures
      within the last 5 years. One patient got epilepsy before other signs of MS. In
      patients with relapsing-remitting MS (RRMS) at onset and active epilepsy (n=10),
      70% had converted to secondary progressive (SPMS) at prevalence date, compared to
      only 35% of those without active epilepsy (p=0.02). 43% had converted to SPMS
      before they got epilepsy. Attack semiology or electroencephalogram recordings
      indicated a focal onset of seizures in 12 of 14 (86%) with active epilepsy.
      CONCLUSION: The frequency of active epilepsy among MS patients in Nordland was
      3.2%, approximately 4.5 times higher than in the general Norwegian population.
      RRMS patients with active epilepsy had more likely converted to SPMS than
      patients without active epilepsy. With a high frequency of focal epilepsy, the
      study supports that focal MS brain pathology is the cause of the comorbid
      epilepsy.

PMID- 29031195
TI  - Ginsenoside Rg3 attenuates cisplatin resistance in lung cancer by downregulating
      PD-L1 and resuming immune.
AB  - Programmed death ligand 1 (PD-L1) as one the most important immune checkpoint was
      verified to involve in chemotherapy resistance in non-small cell lung cancer
      (NSCLC). Ginsenoside Rg3 is isolated from Chinese herb-Panax ginseng which is
      recognized to boost immune and has anti-cancer activity against a majority of
      carcinomas including NSCLC. In this study, we aim to identify whether Rg3 could
      attenuate the PD-L1 expression induced by resistance to cisplatin and draw out
      the underlying mechanisms of PD-L1 in this process. Human lung cancer cell lines
      A549 and A549/DDP (cisplatin-resistance) were used. Cell viability was detected
      by MTT assay, the PD-L1, Akt and NF-kappaB p65 protein expression were detected
      using Western blot analysis, the T cells cytotoxity to tumor cells was detected
      by crystal violet staining living residual tumor cells after coculture of tumor
      cells and T cells. The results showed that Rg3 could inhibit the growth and
      alleviate the resistant to cisplatin of A549/DDP cells. PD-L1 was overexpression
      in A549/DDP cells than A549 cells. Rg3 could decrease the PD-L1 expression
      induced by chemoresistance and resume the T cells cytotoxity to cancer cells. NF
      kappaB p65 and Akt were involved in the PD-L1 overexpression and restrained by
      Rg3. Therefore, Rg3 could be regarded as a new agent targeting PD-L1 in
      chemotherapy refractory NSCLC.

PMID- 29031196
TI  - Anti-edematogenic and anti-inflammatory activity of the essential oil from Croton
      rhamnifolioides leaves and its major constituent 1,8-cineole (eucalyptol).
AB  - The species Croton rhamnifolioides, belonging to the Croton genus, is known in
      ethnomedicine as "quebra faca" and is used in the treatment of stomach pain,
      vomiting and fever. This study aims to evaluate the anti-edematogenic and anti
      inflammatory effect of Croton rhamnifolioides leaf essential oil (OEFC) and its
      major constituent: 1,8-cineole (eucalyptol). The essential oil was extracted from
      fresh leaves through a hydrodistillation system. The chemical analysis was
      determined by gas chromatography-mass spectrometry (GC-MS). The acute anti
      inflammatory activity was determined from the models of: ear edema by the single
      application of croton oil, paw edema induced by: carrageenan, dextran, histamine
      and arachidonic acid, while vascular permeability was determined by Evans blue
      extravasation and chronic anti-inflammatory activity by granuloma induction using
      the implantation of cotton pellets. The GC-MS results identified and quantified
      11 constituents, with the major component being 1,8-cineole (41.33%). The OEFC
      (20mg/mL) and 1,8-cineole (8.26mg/mL) significantly reduced the edema induced by
      croton oil by 42.1 and 34.9%, respectively. The OEFC (25, 50, 100 and 200mg/kg)
      and 1,8-cineole (10.33, 20.66, 41.33 and 82.66mg/kg) statistically reduced paw
      edema induced by carrageenan, dextran as well as vascular permeability (protein
      extravasation). The OEFC (25mg/kg) and 1,8-cineole (10.33mg/kg) demonstrated
      efficacy in reducing edema induced by histamine and arachidonic acid and
      granuloma. In conclusion, the OEFC and 1,8-cineole have anti-inflammatory
      activity in the acute and chronic phase, suggesting therapeutic potential as a
      source for the development of new anti-inflammatory agents.

PMID- 29031197
TI  - Mitochondrial dysfunction is responsible for fatty acid synthase inhibition
      induced apoptosis in breast cancer cells by PdpaMn.
AB  - Targeting cellular metabolism is becoming a hallmark to overcome drug resistance
      in breast cancer treatment. Activation of fatty acid synthase (FASN) has been
      shown to promote breast cancer cell growth. However, there is no concrete report
      underlying the mechanism associated with mitochondrial dysfunction in relation to
      fatty acid synthase inhibition-induced apoptosis in breast cancer cells. The
      current study is aimed at exploring the effect of the novel manganese (Mn)
      complex, labeled as PdpaMn, on lipid metabolism and mitochondrial function in
      breast cancer cells. Herein, we observed that PdpaMn displayed strong
      cytotoxicity on breast cancer cell lines and selectively targeted the tumor
      without affecting the normal organs or cells in vivo. We also observed that
      PdpaMn could bind to TE domain of FASN and decrease the activity and the level of
      expression of FASN, which is an indication that FASN could serve as a target of
      PdpaMn. In addition, we demonstrated that PdpaMn increased intrinsic apoptosis in
      breast cancer cells relayed by a suppressed the level of expression of FASN,
      followed by the release of mitochondrial cytochrome c and the activation of
      caspases-9. Instigated by the above observations, we hypothesized that PdpaMn
      induced apoptosis events are dependent on mitochondrial dysfunction. Indeed, we
      found that mitochondrial membrane potential (MMP) collapse, mitochondrial oxygen
      consumption reduction and adenosine triphosphate (ATP) release were deeply
      repressed. Furthermore, our results showed that PdpaMn significantly increased
      the reactive oxygen species (ROS) production, and the protection conferred by the
      free radical scavenger N-acetyl-cysteine (NAC) indicates that PdpaMn-induced
      apoptosis through an oxidative stress-associated mechanism. More so, the above
      results have demonstrated that mitochondrial dysfunction participated in FASN
      inhibition-induce apoptosis in breast cancer cells by PdpaMn. Therefore, PdpaMn
      may be considered as a good candidate for anti-breast cancer therapeutic option.

PMID- 29031198
TI  - Tretinoin-loaded lipid-core nanocapsules overcome the triple-negative breast
      cancer cell resistance to tretinoin and show synergistic effect on cytotoxicity
      induced by doxorubicin and 5-fluororacil.
AB  - Nanostructured drug delivery systems have been extensively studied, mainly for
      applications in cancer therapy. The advantages of these materials include
      protection against drug degradation and improvement in both the relative
      solubility of poorly water soluble drugs as in targeting of therapy, due to the
      enhanced permeability and retention effect on tumor sites. In this work, we
      evaluate the antitumor activity of tretinoin-loaded lipid core nanocapsules (TT
      LNC) in a tretinoin-resistant breast cancer cell-line, MDA-MB- 231, as well as
      the synergistic effect of combination of this treatment with 5-FU or DOXO. The
      inhibition of cell growth was assayed by MTT reduction. Live/Dead assay and DAPI
      staining evaluated cytotoxicity. Apoptosis was evaluated by Annexin V-PE/7AAD and
      the effect of chronic exposure was evaluated by colony formation assay. TT-LNC
      reduced the cell viability even at lower concentrations (1MUM) and displayed
      synergistic effect with 5-FU or DOXO on cytotoxicity and colony formation
      inhibition. Our work shows a possibility of using nanocapsules to improve the
      antitumoral activity of TT for its use either alone or in combination with other
      chemotherapeutic drugs, especially considering the chronic effect.

PMID- 29031199
TI  - Artesunate attenuates ACLT-induced osteoarthritis by suppressing
      osteoclastogenesis and aberrant angiogenesis.
AB  - Artesunate (ART) is a semi-synthetic derivative of artemisinin and used
      preferentially in treatment of malaria in China. ART has strong anti
      inflammatory, anti-tumor, and anti-angiogenic properties. Although the
      pharmacological effect of ART in osteoarthritis (OA) is unknown, evidence
      suggests that ART might regulate osteoclastogenesis through NF-kappaB signaling.
      In this study we explored the therapeutic effect of ART in an anterior cruciate
      ligament transection (ACLT)-induced OA model. We found that ART effectively
      relieved ACLT-induced osteoarthritis, as demonstrated by the improvement
      expression of pathological genes. We further demonstrated that ART markedly
      reduced OA-associated osteoclastogenesis and angiogenesis. In addition, ART also
      regulated inflammatory response and inhibited the activation of Janus
      Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling in
      ACLT rats. Taken together our study has identified a novel function of ART and
      provided a molecular basis for ART potential applications in the treatment of OA
      and other joint disorders.

PMID- 29031200
TI  - Oleanolic acid methyl ester, a novel cytotoxic mitocan, induces cell cycle arrest
      and ROS-Mediated cell death in castration-resistant prostate cancer PC-3 cells.
AB  - Oleanolic acid derivatives exhibit potent anticancer activities against numerous
      types of cancer. However, the antitumor activity of oleanolic acid methylester
      (OAME), an oleanolic acid derivative, against prostate cancer has not been
      studied. Hence, the present work was conducted to study the anticancer activities
      of OAME. Viability assay showed that treatment of cancer cells with OAME induced
      a significant cell death in concentration- and time-dependent manner. Of note,
      OAME displayed a selective cytotoxicity against cancer cells compared to normal
      epithelial cells. Cells treated with OAME exhibited cell cycle arrest at both G1
      and G2. Apoptotic induction potential of OAME was demonstrated using Annexin V
      assay, caspase activation, and DNA fragmentation methods Mechanistically, the
      results revealed that OAME strongly impacted the intrinsic apoptotic pathway in a
      concentration-dependent manner, as demonstrated by loss of mitochondrial membrane
      potential and release cytochrome c into the cytosol. ROS scavenger completely
      abrogated OAME-induced cell death. In vivo, OAME exerted concentration- dependent
      antiproliferative effect, associated with a significant level of apoptosis,
      potent antiangiogenic activity, and downregulation of survivin. This study
      provides significant insight into the therapeutic activities of OAME against
      prostate cancer in vitro and in vivo, suggesting that OAME might serve as a
      promising lead compound to treat hormonal-resistant prostate cancer.

PMID- 29031201
TI  - Long non-coding RNA OR3A4 promotes proliferation and migration in breast cancer.
AB  - More and more researches have shown the vital functions of long non-coding RNAs
      (LncRNAs) in modulating the biological progresses in tumorigenesis. OR3A4 is such
      a type of lncRNA. The long non-coding RNA (lncRNA) OR3A4 has recently been
      exposed to be exceptionally expressed and referred to the development of several
      cancers. Nevertheless, the biological function and clinical significance of OR3A4
      in the carcinogenesis of breast cancer (BC) are still blurry. Therefore, we
      carried out the following study to make sure the underlying functions of OR3A4 in
      breast cancer. In this article, by means of qRT-PCR assay, we found that OR3A4
      was over-expressed in human breast cancer tissues and cell lines and associated
      with clinicopathological characteristics. In addition, we also found that the
      silence of OR3A4 suppressed the proliferation of breast cancer cells by
      influencing cell cycle and apoptosis, and repressed the cell metastasis via EMT,
      which was contrary to the results in cells transfected with pcDNA-OR3A4. And all
      the functions of OR3A4 in breast cancer were realized in the transcriptional
      level according to the subcellular fractionation location assay. Thus, based upon
      all of the data above, our study might provide a better understanding of the
      pathogenesis of breast cancer and implied that OR3A4 might be a potent prognostic
      and therapeutic target in breast cancer.

PMID- 29031202
TI  - Targeting of cell cycle and let-7a/STAT3 pathway by niclosamide inhibits
      proliferation, migration and invasion in oral squamous cell carcinoma cells.
AB  - The low median survival rate of oral squamous cell carcinoma (OSCC) is associated
      with chemotherapeutic resistance. Niclosamide is an oral anti-helminthic drug,
      its anti-cancer effect has been reported in recent years. However, the effect of
      niclosamide on OSCC remains largely unknown. In this study, we, for the first
      time, investigated the underlying mechanisms from cell cycle arrest and let
      7a/STAT3 axis through CCK-8, cell cycle, apoptosis, wound healing, Transwell
      invasion, generation of stable cell line, real-time PCR, and western blot assays
      using two OSCC cell lines WSU-HN6 and Tca83. We showed that niclosamide could
      inhibit OSCC cells proliferation through causing cell cycle arrest in G1 phase
      and promoting apoptosis, while the cell cycle-related proteins MCM2, MCM7, CDK2
      and CDK4 were downregulated and the apoptosis-related proteins p53 and cleaved
      caspase-3 were upregulated. Furthermore, niclosamide could inhibit migration and
      invasion of OSCC through upregulation of let-7a expression and downregulation of
      p-STAT3 expression. What is more, we established the stably expressing let-7a
      cell line (HN6-let-7a). Like niclosamide, HN6-let-7a could decrease the ability
      of the cell migration, invasion as well as the expression of p-STAT3.
      Collectively, our study finds the new mechanisms that niclosamide inhibits OSCC
      proliferation through causing cell cycle arrest in G1 phase via downregulation of
      the above cell cycle-related genes; promotes OSCC apoptosis through upregulation
      of pro-apoptotic genes; decreases migration and invasion of OSCC by let-7a/STAT3
      axis, thus providing a preferred therapeutic candidate for OSCC in future.

PMID- 29031203
TI  - Local anaesthetic pain relief therapy: In vitro and in vivo evaluation of a
      nanotechnological formulation co-loaded with ropivacaine and dexamethasone.
AB  - Combination therapy is frequently applied to anesthesia and analgesia for its
      benefits, which includes prolonged analgesia following peripheral nerve blockade,
      and reduced side effects. The aim of this study was to develop chitosan (CH)
      coated poly(epsilon-caprolactone) (PCL) nanoparticles to co-deliver ropivacaine
      (RPV) and dexamethasone (DEM) (RPV/DEM CH-PCL NPs) for the prolongation of
      anesthesia and pain relief. In the present study, RPV/DEM CH-PCL NPs were
      fabricated. The properties of CH-PCL NPs were evaluated for their particle sizes,
      zeta potential, drug loading capacity and in vitro drug release profile. In vitro
      skin permeation and in vivo therapeutic effect in an animal model were further
      investigated. The results showed that the NPs was around 190nm, with PDI of less
      than 0.20. The zeta potentials of NPs were about 36mV. In vitro drug release of
      both RPV and DEM from NPs complied with sustained behaviors. All of the drugs
      loaded NPs samples studied exhibited no obvious L929 cells cytotoxicity. In vitro
      skin penetration profiles showed the amount of RPV permeated through the skin
      from NPs was significantly higher than free RPV. RPV and DEM co-loaded NPs
      induced remarkably better anesthetic effect than non DEM loaded RPV CH-PCL NPs.
      The results suggested that adding a small dosage of DEM could improve the
      anesthesia efficacy of RVP to a large content. The resulting formulation could be
      applied as a promising anesthesia system for local anesthetics therapy.

PMID- 29031204
TI  - Ginkgetin inhibits growth of breast carcinoma via regulating MAPKs pathway.
AB  - The purpose of present study was to investigate anti-tumor activity of Ginkgetin
      (GK) and its mechanism of action in breast cancer. The effects of GK on growth of
      human breast cancer cell lines MDA-MB-231, BT-474 and MCF-7 were examined by MTT
      assay. Cells apoptosis in MCF-7 cells were analyzed by TUNEL staining and annexin
      V and propidium iodide double staining. The effects of GK on expression of
      apoptotic associated proteins and mitogen-activated protein kinases (MAPKs) were
      determined by western blotting. The results showed that GK significantly
      inhibited proliferation of MDA-MB-231, BT-474 and MCF-7 cells in vitro with time
      and dose dependent manners and induced apoptosis in MCF-7 cells. GK treatment
      obviously induced the tumor cells apoptosis and inhibited tumor growth in the MCF
      7 xenograft nude mice. GK increased expression of Bax, cleaved-caspase-3, cleaved
      caspase-8, cleaved-caspase-9, cleaved-PARP, and decreased the levels of Bcl-2 and
      survivin in MCF-7 cells. Moreover, GK treatment up-regulated expression of
      phospho extracellular-related kinase (p-ERK), p-p38 and phospho Jun-amino
      terminal kinase (p-JNK) in MCF-7 cells in vitro, and increased numbers of p-p38,
      p-JNK and p-ERK positive cells in the tumor tissue in vivo. Strikingly, treatment
      of p38 inhibitor (or JNK inhibitor; ERK inhibitor) significantly prevented GK
      induced growth inhibition and apoptosis in MCF-7 cells. Collectively, our data
      exhibit GK exerts well anticancer effects in breast cancer cells, which at least
      in part, is via activation of the MAPKs. Our results provide a new approach for
      the treatment of breast cancer.

PMID- 29031205
TI  - Protective effect of alpha-lipoic acid against spleen toxicity of
      dimethylnitrosamine in male mice: Antioxidant and ultrastructure approaches.
AB  - The alpha-lipoic acid is a soft material and useful for the potential biomedical
      applications. The study was aimed to assess the potency of alpha-lipoic acid
      (ALA) against the toxicity of dimethylnitrosamine (DMN) on spleen of mice by
      assessing the antioxidants, histopathological and ultrastructure changes. The
      experiment was achieved on six groups of male mice as following; groups 1, 2, 3,
      and 4 were served as a control, ALA groups, low dose of DMN (DMN-LD; 2mgkg-1) and
      high dose of DMN (DMN-HD; 4mgkg-1). Group 5 was received DMN-LD plus ALA and
      group 6 was given DMN-HD plus ALA. The results indicated that DMN elevated lipid
      peroxidation, xanthine oxidase, nitric oxide, and decline the antioxidant enzymes
      as well as raise the C-reactive protein and tumor necrosis factor. A critical
      obstruction was harmonized with a reduced in lymphocyte number in the white pulp
      were observed. All the lymphatic nodules appeared smaller in DMN-HD group. In
      spleen tissues, marked changes of rough endoplasmic reticulum and appearance of
      three large lymphocytes were noticed. ALA/DMN treatments were improved all the
      oxidative damage and the ultrastructure changes. The data evince that ALA was
      eliminated the adverse effects of DMN on spleen of mice.

PMID- 29031206
TI  - Inhibitory effect of Triperygium wilfordii polyglucoside on dipeptidyl peptidase
      I in vivo and in vitro.
AB  - BACKGROUD: Dipeptidyl peptidase I (DPPI), a lysosomal cysteine protease is
      derived from granule immune cells including mast cell, neutrophils, and toxicity
      T cells. DPPI can activate serine proteases by removal of dipeptides from N
      termini of the pro-proteases, resulting in granule immune cells activation which
      involved in physiological or pathological responses. Triperygium Wilfordii
      Polyglucoside (TWP) is one of the traditional Chinese medicines, and commonly
      used in rheumatoid arthritis (RA) treatment. The present study intended to
      evaluate the effects of TWP on DPPI activity. METHODS: In vivo and in vitro
      studies were carried out to investigate the functions of TWP or triptolide (TP)
      on DPPI activities in serum, tissues of CIA rats. Rats were divided into five
      groups randomly: normal group, untreated CIA rat group, TWP treatment CIA groups
      (the low dose 2.5mg/100g body-weight and high dose 5mg/100g body-weight), and TP
      treatment CIA group (4MUg/100g body-weight). Arthritis development was monitored
      visually, and joint pathology was examined radiologically. Total protein
      concentrations in synovial fluids (SFs) were determined by BCA method. Serums and
      tissue homogenates from CIA rats were collected and DPPI activities were detected
      using fluorescence substrate GF-AFC. The in vitro interactions between DPPI in
      serums or in tissue homogenates and TWP or TP were assessed. RESULTS: TWP-treated
      CIA rats showed a significant improvement in bone erosion. TWP significantly
      suppressed paw swelling and total protein concentration in the SFs of CIA rats
      compared with untreated CIA rats. The elevated activities of DPPI in serums or
      tissues of CIA rats were significantly inhibited by TWP, but not by TP in vivo.
      The inhibitory effects of TWP on DPPI activities were also confirm by in vitro
      study. CONCLUSION: One of the therapeutic functions of TWP in RA treatment could
      be inhibiting DPPI activity in serums and synovial tissue produced during RA
      development, and then reducing inflammatory serine proteases activities and
      further recovering CIA rats from RA symptoms.

PMID- 29031207
TI  - MicroRNA-25 inhibits high glucose-induced apoptosis in renal tubular epithelial
      cells via PTEN/AKT pathway.
AB  - Diabetic nephropathy (DN) has become the major cause of end-stage renal disease
      (ESRD). It has been demonstrated that apoptosis of renal tubular epithelial cells
      induced by hyperglycemia contributes to the pathogenesis of DN. Recent researches
      have corroborated the critical roles of microRNAs (miRNAs) in the apoptosis of
      various types of cells including renal tubular epithelial cells. However, the eff
      ; ;ect of miRNAs on the hyperglycemia-induced apoptosis of renal tubular
      epithelial cells remains unclear. The aim of this study is to explore the eff ;
      ;ect of miRNAs on the hyperglycemia-induced apoptosis of renal tubular epithelial
      cells and its molecular mechanism. Using a miRNA microarray, miRNAs putatively
      associated with DN were examined in renal biopsy tissue samples from DN patients
      and healthy controls. Validation analysis of miR-25 level in serum samples and
      renal biopsy tissue samples was performed using quantitative reverse
      transcription PCR (qRT-PCR). Then, gain- and loss- of function experiments were
      performed to determine the protective roles of miR-25 in high glucose-induced
      damage to renal tubular epithelial cells. Furthermore, the target gene of miR-25
      and the downstream signaling pathway were also investigated. Microarray analysis
      and qRT-PCR revealed that miR-25 was significantly downregulated in renal biopsy
      tissue and serum samples from DN patients. We also observed that an inverse
      relationship between serum miR-25 level and proteinuria in DN patients.
      Meanwhile, miR-25 was decreased in human kidney (HK-2) cells subjected to HG
      treatment in a time dependent manner. Its overexpression reduced production of
      reactive oxygen species (ROS), suppressed cell apoptosis in HG-induced cell
      damage model, which was coupled with the decreased expression of cleaved caspase
      3 and activity of caspase-3. Subsequent analyses demonstrated that phosphatase
      and tensin homolog deleted on chromosome ten (PTEN) was a direct and functional
      target of miR-25, which was validated by the dual luciferase reporter assay. Most
      importantly, the overexpression of PTEN effectively reversed the protective
      effects of miR-25 mimics on renal tubular epithelial cell injury. We also found
      that the anti-apoptotic effects of miR-25 are dependent on the activation of
      PTEN/Akt pathway. In addition, we observed that PTEN was upregulated in renal
      biopsy tissue samples from patients with DN, and an inverse relationship was
      found between PTEN and miR-25 expression, suggesting that miR-25 may exert its
      function through regulation of PTEN in DN. Taken together, our study proved that
      overexpression of miR-25 could ameliorate HG-induced oxidative stress and
      apoptosis in renal tubular epithelial cells through activation of PTEN/AKT
      pathway, suggesting that overexpression of miR-25 might provide a potential
      therapeutic approach for DN.

PMID- 29031208
TI  - Phytoecdysteroids from Ajuga iva act as potential antidiabetic agent against
      alloxan-induced diabetic male albino rats.
AB  - The present study investigated the protective effect of phytoecdysteroids
      extracted from the Ajuga iva plant on body weight changes, blood glucose, insulin
      total protein, blood urea nitrogen (BUN), creatinine, triglycerides (TG),
      cholesterol, lipid peroxidation, antioxidant enzymes, pancreatic histopathology
      and hexokinase-I expression in the alloxan-induced diabetic rats. Experimental
      diabetes was induced following 15day intraperitoneal administration of alloxan.
      The rats were divided into four groups. Group I served as a sham group, and group
      II served as the diabetic control. Group III served as a treatment for
      phytoecdysteroids (10mg/kg), and group IV served as a treatment for
      phytoecdysteroids (20mg/kg). Phytoecdysteroids restored body weight loss to its
      antihyperglycemic effect. Blood glucose was reduced 19.2 and 52.9% in group III
      and IV respectively. Blood insulin (54.9 and 105.88%) and total protein (25 and
      72.2%) was increased in group III and IV respectively. BUN, creatinine, TG,
      cholesterol and lipid peroxidation was significantly reduced following treatment.
      Catalase, superoxide dismutase (SOD), and glutathione peroxidase activity were
      significantly increased following treatment. Islet beta-cells are lost in alloxan
      induced diabetic rats. Regeneration of islets and reduced atrophy of acinar cells
      were noted. The number of insulin-secreting cells was tremendously reduced in
      alloxan-induced diabetic rats. Insulin-secreting cells were increased 48 and 61%
      in group III and IV respectively. Hexokinase-I mRNA (28.3 & 93.5%) and protein
      (27.9 and 55.3%) expression were significantly increased following treatment.
      Taking all these data together, it is suggested that the phytoecdysteroid could
      be a potential therapeutic agent against experimental diabetes.

PMID- 29031209
TI  - Relative value of three whole-body MR approaches for PET-MR, including
      gadofosveset-enhanced MR, in comparison to PET-CT.
AB  - PURPOSE: Evaluate MR protocol for PET-MR including coronal DWI (cDWI), fat
      suppressed T2 (T2w), and gadofosveset-enhanced T1 (CE). MATERIALS AND METHODS: 18
      patients underwent same-day PET-CT and PET-MR. Image quality and performance of
      each sequence, and combination of all three sequences, was evaluated with respect
      to PET-CT. RESULTS: Lesion conspicuity was best on cDWI, while delineation was
      best on CE. Considering all three sequences combined, both readers showed good
      sensitivity and specificity (>80%). Relative sensitivity was highest on CE and
      lowest on T2w. CONCLUSIONS: Whole-body MR performed well in detecting malignant
      lesions compared to PET-CT. CE showed overall highest performance.

PMID- 29031210
TI  - Effect of photoactivated riboflavin on the biodegradation-resistance of root
      dentin collagen.
AB  - This study was conducted to evaluate the effect of UVA-activated 1% riboflavin
      solution on structural integrity; mechanical properties and stability; and
      collagenase-mediated collagen solubilisation resistance of demineralized root
      dentin collagen matrix. Root dentin specimens demineralized with 17% EDTA for
      7days were treated with 1% RF for 1min followed by UVA photo-activation at
      intensity 7mW/cm2 for 1min. Control specimens were completely devoid of
      riboflavin and/or UVA treatments. Specimens were challenged with bacterial
      collagenase type-I solution for different time-periods at 37 degrees C. Collagen
      solubilisation resistance was evaluated in terms of hydroxyproline (HYP)
      liberation. Mechanical characterization of dentin specimens before and after 24h
      of exposure to collagenase solution was done in terms of apparent-elastic modulus
      (Eappr) and ultimate tensile strength (UTS). Variations in dentin collagen
      network structure with exposure time in collagenase were visualized by TEM.
      Crosslinking dentin with UVA-activated riboflavin significantly decreased HYP
      release and increased Eappr and UTS compared to control specimens with storage
      time in collagenase. Moreover, crosslinked specimens showed higher structural
      resistance to collagenase effect reflected from dense, well-formed collagen
      fibrils-network with characteristic collagen cross-banding. UVA-activated
      riboflavin treatment increased collagenase-mediated collagen degradation
      resistance and enhanced mechanical stability against collagenase challenges of
      root dentin after EDTA demineralization.

PMID- 29031211
TI  - Cyanidin-3-O-glucoside inhibits the UVB-induced ROS/COX-2 pathway in HaCaT cells.
AB  - Ultraviolet (UV) radiation from sunlight, especially UVB (290-320nm), is one of
      the most important environmental factors that destroys the integrity of the skin
      and causes epidermal cell apoptosis, potentially even leading to skin cancer. UVB
      irradiation can cause skin damage by stimulating inflammatory and apoptotic
      pathways. Anthocyanins are flavonoids that are common in many vegetable foods,
      and have also demonstrated chemopreventive effects. Cyanidin-3-O-glucoside, as a
      typical anthocyanin, exhibits anti-inflammatory and anti-oxidant effects. This
      study aimed to investigate the effects, as well as the underlying mechanisms, of
      treating UVB-exposed HaCaT cells with Cyanidin-3-O-glucoside. We demonstrated
      that Cyanidin-3-O-glucoside could effectively prevent the UVB-induced apoptosis
      of HaCaT cells. This protective effect can be explained by the scavenging of ROS
      and the suppression of COX-2 expression by interaction with the MAPK and Akt
      signaling pathways. Furthermore, we used Celecoxib as a positive control, and
      results showed that Cyanidin-3-O-glucoside was more effective at decreasing EGFR
      phosphorylation than Celecoxib, which translated into a stronger inhibitory
      effect against the downstream elements p38, ERK, and JNK. Taken together, these
      results indicate that Cyanidin-3-O-glucoside can protect HaCaT cells against UVB
      radiation, which could provide a basis for the development of a potent
      nutritional therapy for UVB-induced skin disorders.

PMID- 29031212
TI  - A comprehensive analysis of direct and photosensitized attenuation of Toxoplasma
      gondii tachyzoites.
AB  - In the present work, we have evaluated the effect of three different types of
      radiation: UVC (254+/-5nm), UVA (365+/-20nm) and visible (420+/-20nm) on
      different morphological and biological functions of Toxoplasma gondii
      tachyzoites. Briefly, UVC and UVA showed an inhibitory effect on parasite
      invasion in a dose-dependent manner. UVC showed the strongest effect inducing
      both structural damage (antigens) and functional inhibition (i.e., invasion and
      replication). On its own, visible light induces a quite distinctive and selective
      pattern of parasite-attenuation. This type of incident radiation inhibits the
      replication of the parasite affecting neither the capability of
      invasion/attachment nor the native structure of proteins (antigens) on parasites.
      Such effects are a consequence of photosensitized processes where phenol red
      might act as the active photosensitizer. The potential uses of the methodologies
      investigated herein are discussed.

PMID- 29031213
TI  - Impairment of heart rhythm complexity in patients with drug-resistant epilepsy:
      An assessment with multiscale entropy analysis.
AB  - OBJECTIVE: Epilepsy and seizures can have dramatic effects on the cardiac
      function. The aim of this study was to investigate the heart rhythm complexity in
      patients with drug-resistant epilepsy (DRE). METHODS: Ambulatory 24-h
      electrocardiograms (ECG) from 70 DRE patients and 50 healthy control subjects
      were analyzed using conventional heart rate variability (HRV) and multiscale
      entropy (MSE) methods The variation of complexity indices (CI), which was
      calculated from MSE profile, was determined. RESULTS: DRE patients had
      significantly lower time domain (Mean RR, SDNN, RMSSD, pNN50) and frequency
      domain (VLF, LF, HF, TP) HRV measurements than healthy controls. Of the MSE
      analysis, MSE profile, CI including Slope 5, Area 1-5, Area 6-15 and Area 6-20
      were significantly lower than those in the healthy control group. In receiver
      operating characteristic (ROC) curve analysis, VLF had the greatest
      discriminatory power for the two groups. In both net reclassification improvement
      (NRI) model and integrated discrimination improvement (IDI) models, CI derived
      from MSE profiles significantly improved the discriminatory power of Mean RR,
      SDNN, RMSSD, pNN50, VLF, LF, HF and TP. SIGNIFICANCE: The heart rate complexity
      is impaired for DRE patients. CI are useful to discriminate DRE patients from
      subjects with normal cardiac complexity. These findings indicate that MSE method
      may serve as a complementary approach for characterizing and understanding
      abnormal heart rate dynamics in epilepsy. Furthermore, the CI may potentially be
      used as a biomarker in monitoring epilepsy.

PMID- 29031215
TI  - Comprehensive multipathway risk assessment of chemicals associated with recycled
      ("crumb") rubber in synthetic turf fields.
AB  - BACKGROUND: Thousands of synthetic turf fields in the US are regularly used by
      millions of individuals (particularly children and adolescents). Although many
      safety assessments have concluded that there are low or negligible risks related
      to exposure to chemicals found in the recycled rubber used to make these fields,
      concerns remain about the safety of this product. Existing studies of recycled
      rubber's potential health risks have limitations such as small sample sizes and
      limited evaluation of relevant exposure pathways and scenarios. OBJECTIVE:
      Conduct a comprehensive multipathway human health risk assessment (HHRA) of
      exposure to chemicals found in recycled rubber. METHODS: All available North
      American data on the chemical composition of recycled rubber, as well as air
      sampling data collected on or near synthetic turf fields, were identified via a
      literature search. Ingestion, dermal contact, and inhalation pathways were
      evaluated according to US Environmental Protection Agency (US EPA) guidance, and
      exposure scenarios for adults, adolescents, and children were considered.
      RESULTS: Estimated non-cancer hazards and cancer risks for all the evaluated
      scenarios were within US EPA guidelines. In addition, cancer risk levels for
      users of synthetic turf field were comparable to or lower than those associated
      with natural soil fields. CONCLUSIONS: This HHRA's results add to the growing
      body of literature that suggests recycled rubber infill in synthetic turf poses
      negligible risks to human health. This comprehensive assessment provides data
      that allow stakeholders to make informed decisions about installing and using
      these fields.

PMID- 29031214
TI  - Land use regression models for the oxidative potential of fine particles (PM2.5)
      in five European areas.
AB  - Oxidative potential (OP) of particulate matter (PM) is proposed as a biologically
      relevant exposure metric for studies of air pollution and health. We aimed to
      evaluate the spatial variability of the OP of measured PM2.5 using ascorbate (AA)
      and (reduced) glutathione (GSH), and develop land use regression (LUR) models to
      explain this spatial variability. We estimated annual average values (m-3) of
      OPAA and OPGSH for five areas (Basel, CH; Catalonia, ES; London-Oxford, UK (no
      OPGSH); the Netherlands; and Turin, IT) using PM2.5 filters. OPAA and OPGSH LUR
      models were developed using all monitoring sites, separately for each area and
      combined-areas. The same variables were then used in repeated sub-sampling of
      monitoring sites to test sensitivity of variable selection; new variables were
      offered where variables were excluded (p > .1). On average, measurements of OPAA
      and OPGSH were moderately correlated (maximum Pearson's maximum Pearson's R = =
      .7) with PM2.5 and other metrics (PM2.5absorbance, NO2, Cu, Fe). HOV (hold-out
      validation) R2 for OPAA models was .21, .58, .45, .53, and .13 for Basel,
      Catalonia, London-Oxford, the Netherlands and Turin respectively. For OPGSH, the
      only model achieving at least moderate performance was for the Netherlands (R2 =
      .31). Combined models for OPAA and OPGSH were largely explained by study area
      with weak local predictors of intra-area contrasts; we therefore do not endorse
      them for use in epidemiologic studies. Given the moderate correlation of OPAA
      with other pollutants, the three reasonably performing LUR models for OPAA could
      be used independently of other pollutant metrics in epidemiological studies.

PMID- 29031216
TI  - Description of Neoparamoeba longipodia n. sp. and a new strain of Neoparamoeba
      aestuarina (Page, 1970) (Amoebozoa, Dactylopodida) from deep-sea habitats.
AB  - Two strains of lobose amoebae have been isolated from the deep-sea bottom
      sediments of the Sea of Japan (3.6km deep) and Western Atlantic Ocean (5.1km
      deep). Amoebae of both strains have a dactylopodial mophotype, intracellular
      kinetoplastid symbiont (Perkinsela-like organism) and have no microscales on the
      cell surface. The morphology and molecular data of the Sea of Japan strain allow
      us to unambiguously identify it as Neoparamoeba aestuarina (Page, 1970). At the
      same time, the Atlantic strain is described as a new species Neoparamoeba
      longipodia as it differs from other species of the genus Neoparamoeba in
      morphology and gene sequence data. The data presented expand the range of known
      habitats for the genus Neoparamoeba and permit further analysis of the
      phylogenetic relationships within this clade with the expanded set of molecular
      data.

PMID- 29031218
TI  - Termination patterns of stimulus-induced rhythmic, periodic, or ictal patterns
      and spontaneous electrographic seizures.
AB  - OBJECTIVE: To investigate the ability of the evolution and termination patterns
      to distinguish stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs)
      from spontaneous electrographic seizures, a challenge to the neurophysiologist
      and clinician. METHODS: We screened the prospectively collected database of
      patients undergoing continuous EEG (cEEG) and identified 25 cases of SIRPIDs. We
      compared patients with SIRPIDs to 25 patients with spontaneous seizures. Two
      experienced neurophysiologists graded the termination pattern of both on fast
      fourier transform (FFT) as "abrupt" or "sputtering." RESULTS: The identification
      of a "sputtering" or cyclical tapering pattern accurately discriminated SIRPIDs
      from spontaneous seizures with 88% sensitivity and 87% specificity, yielding a
      positive predictive value of 82% for SIRPIDs when the pattern was present
      (negative predictive value 87% when the sputtering termination was not seen).
      Similarly, the identification of an "abrupt" termination pattern identified
      clinically determined seizures with 84% sensitivity and 88% specificity.
      CONCLUSIONS: The termination pattern quickly and accurately distinguishes SIRPIDs
      from spontaneous seizures, suggesting that at least some SIRPIDs have an
      underlying mechanism distinct from that of spontaneous seizures. SIGNIFICANCE: If
      validated in other studies, the use of evolution and termination patterns to
      classify EEG patterns as epileptiform seizures versus SIRPIDs will help guide
      treatment of these patients.

PMID- 29031217
TI  - Quality of life and burden in caregivers of youth with obsessive-compulsive
      disorder presenting for intensive treatment.
AB  - BACKGROUND: Pediatric obsessive-compulsive disorder (OCD) is associated with
      deleterious familial effects; caregivers are often enmeshed in the disorder and
      can experience considerable burden and decreased quality of life (QoL).
      Consequently, this study examined burden and QoL in caregivers of youth with OCD
      enrolled in an intensive outpatient or partial hospitalization program. METHOD:
      The relationships between caregiver QoL and burden and the following variables
      were investigated: OCD symptom severity, functioning (youth functional
      impairment, general family functioning), family (family accommodation, parental
      relationship satisfaction, positive aspects of caregiving), and comorbid
      psychopathology (caregiver anxiety and depressive symptoms, youth internalizing
      and externalizing behaviors). Seventy-two child and caregiver dyads completed
      clinician- and self-rated questionnaires. RESULTS: Components of caregiver QoL
      correlated with caregiver-rated functional impairment, family accommodation,
      youth externalizing behaviors, and caregiver psychopathology. Aspects of
      caregiver burden correlated with child OCD symptom severity, functional
      impairment related to OCD, as well as caregiver and child comorbid
      psychopathology. Caregiver depressive symptoms predicted caregiver QoL, and
      caregiver depressive symptoms and child externalizing symptoms both predicted
      caregiver burden. Caregiver burden did not mediate the relationship between
      obsessive-compulsive symptom severity and caregiver QoL. CONCLUSION: Ultimately,
      elucidating factors associated with increased caregiver burden and poorer QoL is
      pertinent for identifying at-risk families and developing targeted interventions.

PMID- 29031219
TI  - Long term correlation of subthalamic beta band activity with motor impairment in
      patients with Parkinson's disease.
AB  - OBJECTIVES: To investigate the long term association of subthalamic beta activity
      with parkinsonian motor signs. METHODS: We recruited 15 patients with Parkinson's
      disease undergoing subthalamic DBS for local field potential recordings after
      electrode implantation, and at 3 and 8months post-operatively using the
      implantable sensing enabled Activa PC+S (Medtronic). Three patients dropped out
      leaving 12 patients. Recordings were conducted ON and OFF levodopa at rest. Beta
      (13-35Hz) peak amplitudes were extracted, compared across time points and
      correlated with UPDRS-III hemibody scores. RESULTS: Peaks in the beta frequency
      band (13-35Hz) in the OFF medication state were found in all hemispheres. Mean
      beta activity was significantly suppressed by levodopa at all recorded time
      points (P<0.007) and individual beta power amplitude correlated with parkinsonian
      motor impairment across time points and dopaminergic states (pooled data;
      rho=0.25, P<0.001). CONCLUSIONS: Our results indicate that beta-activity is
      correlated with parkinsonian motor signs over a time period of 8months.
      SIGNIFICANCE: Beta-activity may be a chronically detectable biomarker of symptom
      severity in PD that should be further evaluated under ongoing DBS.

PMID- 29031220
TI  - Effects of glyphosate-based herbicide on pintado da Amazonia: Hematology,
      histological aspects, metabolic parameters and genotoxic potential.
AB  - Roundup Original(r) is an herbicide widely used in Mato Grosso's agriculture and
      it may contamine water bodies, being an unforeseen xenobiotic to aquatic
      organisms, particularly fish. This study investigated the effects on the hybrid
      fish jundiara (Leiarius marmoratus*Pseudoplatystoma reticulatum) of an
      environmentally relevant exposure to this herbicide. Glucose levels in liver,
      muscle and plasma decreased after exposure to 1.357mgL-1 of Roundup Original(r)
      (glyphosate nominal concentration), while glycogen levels reduced in liver and
      muscle for different times. Elevated cholesterol and triglycerides revealed an
      adaptive response. Protein and lactate levels also increased during the
      experiment, however no changes were observed for muscle lactate. Increment of the
      transaminases suggests damage to the liver cells. After 96hours of exposure,
      reductions in all hematological parameters were observed, whereas the
      micronucleus test findings showed genotoxic scenery. Histological analysis did
      not display pathological alterations of the hepatic tissue. The results obtained
      provide valuable data for noticing the effects of pollutants on non-target
      organisms.

PMID- 29031221
TI  - Effects of particulate matter from straw burning on lung fibrosis in mice.
AB  - OBJECTIVE: To investigate the impacts of particulate matter 2.5 (PM2.5) from
      straw burning on the acute exacerbation of lung fibrosis in mice and the
      preventive effects of N-acetylcysteine (NAC). METHODS: The composition, particle
      size, and 30-min concentration change in an exposure system of the PM2.5 from
      straw-burning were determined. Forty C57BL male mice were equally randomized to
      two groups: bleomycin (BLM)-induced lung fibrosis with an exposure to air
      (BLM+air) and BLM+PM2.5 groups. On day 7 after receiving intratracheal injection
      of BLM, mice were exposed to air or PM2.5 in an exposure system for 30min twice
      daily and then sacrificed after one-week or four-week exposure (10 mice/group).
      Mouse survival, lung histopathology, macrophage accumulation in the lung, and pro
      inflammatory cytokine levels in alveolar lavage fluid (ALF) were determined.
      RESULTS: PM2.5 from straw burning were mainly composed of organic matter (74.1%);
      10.92% of the inorganic matter of the PM2.5 were chloride ion; 4.64% were
      potassium ion; other components were sulfate, nitrate, and nitrite. Particle size
      was 10nm-2MUm. Histopathology revealed a greater extent of inflammatory cell
      infiltration in the lung, widened alveolar septum, and lung fibrosis in the
      BLM+PM2.5 group than in the BLM+air group and a greater extent of those adverse
      effects after four-week than after one-week exposure to PM2.5. The BLM+PM2.5
      group also showed macrophages containing particular matter and increased
      pulmonary collagen deposition as the exposure to PM2.5 increased. Interleukin
      (IL)-6 and TNF-alpha levels in ALF were significantly higher in the BLM+PM2.5
      group than in the BLM+air group (P<0.05) and significantly higher after four-week
      exposure than after one-week exposure to PM2.5 (P<0.05). TGF-beta levels in ALF
      after four-week exposure were significantly higher in the BLM+PM2.5 group than in
      the BLM+air group (P<0.05). The levels of IL-6, TNF-alpha, and TGF-beta in
      peripheral serum were not significantly different in the BLM+PM2.5 and BLM+air
      groups. Lung hydroxyproline contents increased as the exposure to PM2.5 increased
      and were significantly higher after four-week than after one-week exposure
      (P=0.019). Exposure to PM2.5 did not affect the survival of normal mice (100%)
      but reduced the survival of mice with BLM-induced IPF (30%), whereas NAC extended
      the survival (70%, vs. BLM+PM2.5, P=0.032). CONCLUSION: Exposure of mice with BLM
      induced IPF to PM2.5 from straw burning exacerbated lung inflammation and
      fibrosis and increased mortality; NAC increased the mouse survival, indicating
      protective effects.

PMID- 29031222
TI  - Apolipoproteins adsorption and brain-targeting evaluation of baicalin
      nanocrystals modified by combination of Tween80 and TPGS.
AB  - To help baicalin pass across BBB and improve its targeting in brain, we designed
      a novel formulation strategy of baicalin nanocrystals that preferentially
      adsorbing apolipoprotein E (ApoE) and repelling protein adsorption of opsonins.
      Intravenous baicalin nanocrystals suspensions (BCL-NS) modified by different
      surfactant were prepared by high-pressure homogenization. The targeting potential
      of surface-modified BCL-NS with mean particles size of about 250nm was assessed
      by in vitro protein adsorption studies using two-dimensional polyacrylamide gel
      electrophoresis (2-D PAGE), and further evaluated in vivo pharmacokinetics. The
      protein adsorption results showed that BCL-NS/TPGS, BCL-NS/TW80 and BCL
      NS/TPGS+TW80 adsorbed very high amounts of apolipoproteins (ApoA-I, ApoA-II, ApoA
      IV, ApoC-III, ApoE, ApoJ) and relative low amounts of opsonins (fibrinogen,
      immunoglobulin heavy chain gamma, immunoglobulin light chain). The
      pharmacokinetics results demonstrated the AUC (0-infinity) in brain of the BCL
      NS/TW80+TPGS was 6.67 times as high as that of the BCL solution, and 2.59 times
      as high as that of the BCL-NS/TW80. It could be attributed to the most ApoE and
      Apo J adsorption indicative of strong BBB penetration, and least IgG gamma and
      fibrinogen loading minimizing the risk of hepatic uptake. Combination of TW80 and
      TPGS can be rational choice of surfactants of baicalin nanocrystals for brain
      targeting mediated by ApoE adsorption.

PMID- 29031223
TI  - Enhanced antibacterial activity and biocompatibility of zinc-incorporated organic
      inorganic nanocomposite coatings via electrophoretic deposition.
AB  - Increased use of reconstruction procedures in orthopedics has improved the life
      of patients undergoing surgery. However, surgical site infection remains a major
      challenge. Efforts were made to fabricate antibacterial surfaces with good
      biocompatibility. This present study aimed to fabricate zinc-incorporated
      chitosan/gelatin (CS/G) nanocomposite coatings on the titanium substrates via
      electrophoretic deposition (EPD). Physicochemical characterization confirmed that
      zinc was successfully deposited in a metallic oxide/salt complex status.
      Transmission electron microscopic (TEM) results observed formation of core-shell
      nanosized particles released from the coatings. The selected-area electron
      diffraction (SAED) pattern of the particles presented faces of ZnO with organic
      background. Mechanical tests showed improved tensile and shear bond strength
      between substrates and zinc-incorporated coating surfaces. Zinc-incorporated CS/G
      coatings presented antibacterial abilities against both Gram-negative E. coli and
      Gram-positive S. aureus in a concentration-dependent manner. The generation of
      ZnO/Zn2+ complex in the coatings may contribute to bacteria inhibition. In vitro
      study demonstrated that appropriate concentration of zinc could promote
      proliferative and osteogenic activities of rat bone marrow stromal cells. The
      present study suggested that zinc-incorporated CS/G coating was a promising
      candidate for surface modification of biomedical materials.

PMID- 29031224
TI  - Direct one-pot synthesis of cinnamaldehyde immobilized on gold nanoparticles and
      their antibiofilm properties.
AB  - The objective of the present study was to develop a one-pot strategy to synthesis
      gold nanoparticle complexes using cinnamaldehyde, a potent antibiofilm agent
      which in its free form, exhibits high volatility and unstable nature. Hence, we
      developed cinnamaldehyde gold nanoparticles (CGNPs) in a single step to overcome
      the limitations of free cinnamaldehyde. Furthermore, reduction abilities of
      cinnamaldehyde under different experimental conditions, that is, varying
      precursor concentrations of cinnamaldehyde and gold, metal salts, pH,
      temperature, and light sources, were investigated. UV-vis spectroscopy,
      transmission electron microscopy, attenuated total reflectance Fourier transform
      infrared spectroscopy, and dynamic light-scattering measurements revealed that
      heat influenced the nanoparticle formation in the presence of cinnamaldehyde, and
      as produced cinnamaldehyde immobilized on gold nanoparticles were spherical,
      monodispersed, and stable by surface charge. CGNPs containing 0.01%
      cinnamaldehyde by weight exhibited effective biofilm inhibition of up to >80%
      against Gram positive bacteria (methicillin-sensitive and -resistant strains of
      Staphylococcus aureus, MSSA and MRSA, respectively) and Gram negative
      (Escherichia coli and Pseudomonas aeruginosa) and a fungus Candida albicans. In
      addition, CGNPs attenuated the virulence of C. albicans by inhibiting hyphae
      formation. Based on observations of their antibiofilm effects and confocal
      microscopy findings, CGNPs caused biofilm damage by direct contact. Thus,
      cinnamaldehyde appears to be a promising reduction material for the eco-friendly,
      one-pot synthesis of CGNPs with excellent antibiofilm activity.

PMID- 29031225
TI  - Cube-shaped theranostic paclitaxel prodrug nanocrystals with surface
      functionalization of SPC and MPEG-DSPE for imaging and chemotherapy.
AB  - As one of nanomedicine delivery systems (NDSs), drug nanocrystals exhibited an
      excellent anticancer effect. Recently, differences of internalization mechanisms
      and subcellular localization of both drug nanocrystals and small molecular free
      drug have drawn much attention. In this paper, paclitaxel (PTX) as a model
      anticancer drug was directly labeled with 4-chloro-7-nitro-1, 2, 3-benzoxadiazole
      (NBD-Cl) (a drug-fluorophore conjugate Ma et al. (2016) and Wang et al. (2016)
      [1,2] (PTX-NBD)). PTX-NBD was synthesized by nucleophilic substitution reaction
      of PTX with NBD-Cl in high yield and characterized by fluorescence, XRD, ESI-MS,
      and FT-IR analysis. Subsequently, the cube-shaped PTX-NBD nanocrystals were
      prepared with an antisolvent method followed by surface functionalization of SPC
      and MPEG-DSPE. The obtained specific shaped PTX-NBD@PC-PEG NCs had a hydrodynamic
      particle size of ~50nm, excellent colloidal stability, and a high drug-loading
      content of ~64%. Moreover, in comparison with free PTX-NBD and the sphere-shaped
      PTX-NBD nanocrystals with surface functionalization of SPC and MPEG-DSPE (PTX
      NBD@PC-PEG NSs), PTX-NBD@PC-PEG NCs remarkably reduced burst release and improved
      cellular uptake efficiency and in vitro cancer cell killing ability. In a word,
      the work highlights the potential of theranostic prodrug nanocrystals based on
      the drug-fluorophore conjugates for cell imaging and chemotherapy.

PMID- 29031226
TI  - Ectopic vascularized bone formation by human mesenchymal stem cell microtissues
      in a biocomposite scaffold.
AB  - Three-dimensional multicellular human bone marrow mesenchymal stem cells (hBM
      MSCs) are showing a great promise in the repair of bone tissue due to its
      osteogenic differentiation potential, mimicking in vivo microenvironment and
      immunomodulatory property. In the present study, the potential of hBM-MSC
      microtissues (MTs) in combination with a biocomposite material to form
      vascularized bone-like tissue at an ectopic site in an immunocompromised mouse
      was evaluated. The scaffold was fabricated using gelatin, carboxymethyl
      cellulose, polyvinyl alcohol and nano-hydroxyapatite (GCnHP) by the freeze-drying
      method. The physico-chemico-biological characteristics were compared with control
      scaffold devoid of polyvinyl alcohol (GCnH). The scaffolds (GCnH and GCnHP) were
      highly porous and had interconnected pores. GCnHP showed higher mechanical
      strength, higher water adsorption and a lower rate of collagenase-mediated
      degradation in comparison to GCnH. The scaffolds also supported growth and
      proliferation of hBM-MSCs MTs and subsequent differentiation into osteoblast-like
      cells. The differentiated cells showed matrix mineralization and high expression
      of runX2, alkaline phosphatase, collagen type 1 and osteocalcin genes. A high
      expression of VEGF was also observed suggesting the potential of hBM-MSC MTs to
      induce angiogenesis. H&E and Masson's trichrome staining of the 4-weeks in vivo
      implanted scaffold revealed the presence of newly synthesized collagen and
      infiltration of host vasculature. IHC assessment showed expression of osteocalcin
      and osterix. These results demonstrate the efficacy of the combination of hBM-MSC
      MTs and biocomposite material as a promising approach for in vivo non-load
      bearing bone tissue repair for future clinical and various regenerative medicine
      applications.

PMID- 29031227
TI  - Development of a graphene oxide/chitosan nanocomposite for the removal of picric
      acid from aqueous solutions: Study of sorption parameters.
AB  - The functionalization of graphene oxide (GO) with chitosan (Chi) has been
      investigated to prepare a nanocomposite material (GO-Chi) for the removal of
      picric acid from aqueous solutions. Materials were characterized by FT-IR, TGA,
      DTG, FESEM, EDX, XRD and BET. Batch experiments such as solution pH, amount of
      adsorbents, contact time, concentration of the picric acid and temperature were
      achieved to study sorption process. Kinetic studies were well described by pseudo
      second-order kinetic model for both adsorbents. Isotherm studies showed that the
      Langmuir isotherm for GO and Freundlich and Halsey models for GO-Chi were found
      to best represent the measured sorption data. Negative DeltaG degrees  values for
      GO-Chi and positive ones for GO indicated the nature of spontaneous and
      unspontaneous, respectively for adsorption process. In addition, picric acid
      molecules can be desorbed from GO-Chi up to 80% at pH=9 and that the consumed GO
      Chi could be reutilized up to 5th cycle of regeneration.

PMID- 29031228
TI  - Peptide-based electrochemical biosensor for juvenile idiopathic arthritis
      detection.
AB  - Juvenile idiopathic arthritis (JIA) is a wide group of diseases, characterized by
      synovial inflammation and joint tissue damage. Due to the delay in the
      implementation of biomarkers into clinical practice and the association with
      severe sequels, there is an imperative need for new JIA diagnosis strategies.
      Electrochemical biosensors based on screen-printed electrodes and peptides are
      promising alternatives for molecular diagnosis. In this work, a novel biosensor
      for detecting juvenile idiopathic arthritis (JIA) was developed based on the
      immobilization of the PRF+1 mimetic peptide, as recognition biological element,
      on the surface of screen-printed carbon electrode. This biosensor was able to
      discriminate the JIA positive and negative serum samples from different
      individuals using differential pulse voltammetry, presenting limits of detection
      and quantification in diluted samples of 1:784 (v/v) and 1:235 (v/v),
      respectively. Evaluation by electrochemical impedance spectroscopy showed RCT 3
      times higher for JIA positive sample than for a pool of human serum samples from
      healthy individuals. Surface analysis of the biosensor by atomic force
      microscopy, after contact with JIA positive serum, presented great globular
      clusters irregularly distributed. The long-term stability of the biosensor was
      evaluated, remaining functional for over 40 days of storage (after storage at 8
      degrees C). Therefore, a simple, miniaturized and selective biosensor was
      developed, being the first one based on mimetic peptide and screen-printed carbon
      electrode, aiming at the diagnosis of the juvenile idiopathic arthritis in real
      serum samples.

PMID- 29031229
TI  - [99mTc]duramycin for cell death imaging: Impact of kit formulation, purification
      and species difference.
AB  - INTRODUCTION: [99mTc]duramycin is a SPECT tracer for cell death imaging. We
      evaluated the impact of kit formulation, purification and species difference on
      the pharmacokinetic profile and cell death targeting properties of
      [99mTc]duramycin in order to define the optimal conditions for (pre-)clinical
      use. METHODS: Three kits were prepared (A: traditional formulation, B: containing
      1/3 of ingredients, C: containing HYNIC-PEG12-duramycin). Following labeling, the
      kits were used without purification, or with SPE or HPLC purification. The
      pharmacokinetic profile was evaluated in mice and rats at 24 h post tracer
      injection (p.i.). Non-specific accumulation of [99mTc]duramcyin was studied by
      MUSPECT imaging in chemotherapy treated COLO205 tumor bearing mice pre-treated
      with cold duramycin (0.01-50 MUg). Cell death targeting ability of the kits
      displaying the best pharmacokinetic profile was compared in a treatment response
      study in COLO205 tumor bearing mice treated with conatumumab (anti-DR5 antibody).
      RESULTS: HPLC purification of kit prepared [99mTc]duramycin and reducing the
      amount of kit ingredients resulted in the best pharmacokinetic profile with low
      accumulation in liver, spleen and kidneys. The use of PEGylated [99mTc]duramycin
      required longer circulation times (> 4 h pi) to obtain good imaging
      characteristics. Pre-treatment with duramycin significantly decreased tracer
      uptake in chemotherapy treated tumors in a dose-dependent manner. A blocking dose
      of 50 MUg significantly increased non-specific accumulation in liver and spleen.
      Non-specific accumulation of [99mTc]duramycin was however demonstrated to be
      species dependent. HPLC purified kit A (5.21+/-1.71 %ID/cc) and non-purified kit
      B (1.68+/-0.46 %ID/cc) demonstrated a significant increase in tumor uptake
      compared to baseline following conatumumab treatment. CONCLUSIONS: To obtain
      [99mTc]duramycin with favorable imaging characteristics for cell death imaging in
      mice [99mTc]duramycin needs to be prepared with high specific activity by
      applying HPLC purification. The need for HPLC purification appears to be a
      species dependent phenomenon and might therefore not be required for clinical
      translation.

PMID- 29031231
TI  - Does adolescents' psychopathology change in times of change?

PMID- 29031230
TI  - Astatine-211 labeled anti-HER2 5F7 single domain antibody fragment conjugates:
      radiolabeling and preliminary evaluation.
AB  - INTRODUCTION: Derived from heavy chain only camelid antibodies, ~15-kDa single
      domain antibody fragments (sdAbs) are an attractive platform for developing
      molecularly specific imaging probes and targeted radiotherapeutics. The rapid
      tumor accumulation and normal tissue clearance of sdAbs might be ideal for use
      with 211At, a 7.2-h half-life alpha-emitter, if appropriate labeling chemistry
      can be devised to trap 211At in cancer cells after sdAb binding. This study
      evaluated two reagents, [211At]SAGMB and iso-[211At]SAGMB, for this purpose.
      METHODS: [211At]SAGMB and iso-[211At]SAGMB, and their radioiodinated analogues
      [131I]SGMIB and iso-[131I]SGMIB, were synthesized by halodestannylation and
      reacted with the anti-HER2 sdAb 5F7. Radiochemical purity, immunoreactivity and
      binding affinity were determined. Paired-label internalization assays on HER2
      expressing BT474M1 breast carcinoma cells directly compared [131I]SGMIB
      5F7/[211At]SAGMB-5F7 and iso-[131I]SGMIB-5F7/iso-[211At]SAGMB-5F7 tandems. The
      biodistribution of the two tandems was evaluated in SCID mice with subcutaneous
      BT474M1 xenografts. RESULTS: Radiochemical yields for Boc2-iso-[211At]SAGMB and
      Boc2-[211At]SAGMB synthesis, and efficiencies for coupling of iso-[211At]SAGMB
      and [211At]SAGMB to 5F7 were similar, with radiochemical purities of [211At]SAGMB
      5F7 and iso-[211At]SAGMB-5F7 >98%. iso-[211At]SAGMB-5F7 and [211At]SAGMB-5F7 had
      immunoreactive fractions >80% and HER2 binding affinities of less than 5 nM.
      Internalization assays demonstrated high intracellular trapping of radioactivity,
      with little difference observed between corresponding 211At- and 131I-labeled 5F7
      conjugates. Higher BT474M1 intracellular retention was observed from 1-6 h for
      the iso-conjugates (iso-[211At]SAGMB-5F7, 74.3 +/- 2.8%, vs. [211At]SAGMB-5F7,
      63.7 +/- 0.4% at 2 h) with the opposite behavior observed at 24 h. Peak tumor
      uptake for iso-[211At]SAGMB-5F7 was 23.4 +/- 2.2% ID/g at 4 h, slightly lower
      than its radioiodinated counterpart, but significantly higher than observed with
      [211At]SAGMB-5F7. Except in kidneys and lungs, tumor-to-normal organ ratios for
      iso-[211At]SAGMB-5F7 were greater than 10:1 by 2 h, and significantly higher than
      those for [211At]SAGMB-5F7. CONCLUSION: These 211At-labeled sdAb conjugates,
      particularly iso-[211At]SAGMB-5F7, warrant further evaluation for targeted alpha
      particle radiotherapy of HER2-expressing cancers.

PMID- 29031232
TI  - Does prior domain-specific content knowledge influence students' recall of
      arguments surrounding interdisciplinary topics?
AB  - Awareness of various arguments can help interactants present opinions, stress
      points, and build counterarguments during discussions. At school, some topics are
      taught in a way that students learn to accumulate knowledge and gather arguments,
      and later employ them during debates. Prior knowledge may facilitate recalling
      information on well structured, fact-based topics, but does it facilitate
      recalling arguments during discussions on complex, interdisciplinary topics? We
      assessed the prior knowledge in domains related to a bioethical topic of 277
      students from Germany (approximately 15 years old), their interest in the topic,
      and their general knowledge. The students read a text with arguments for and
      against prenatal diagnostics and tried to recall the arguments one week later and
      again six weeks later. Prior knowledge in various domains related to the topic
      individually and separately helped students recall the arguments. These
      relationships were independent of students' interest in the topic and their
      general knowledge.

PMID- 29031233
TI  - Forensic and clinical significance of serum amylase, lipase and gamma glutamyl
      transferase as predictors of outcome in head injured patients.
AB  - : Head trauma is one of the leading causes of death and disability worldwide.
      Combined head lesions consist of more than one form of lesions. Biochemical
      markers of brain injury are used in determining the extent of brain injury and
      predicting its outcomes. The aim of this study was to investigate the forensic
      and clinical significance of serum amylase, lipase and gamma glutamyl transferase
      (GGT) as predictors of the outcome in head injured patients. PATIENTS AND
      METHODS: Sixty head injured patients were enrolled and subjected to personal
      history taking, general and local physical examination. Glasgow coma scale (GCS),
      head computed tomography scan and pelvi-abdominal ultrasound were performed. Two
      blood samples (each 3 mL) were drawn at the time of admission and after 24 h for
      measuring serum amylase, lipase and GGT levels using special kits. RESULTS: Most
      cases of head trauma occurred accidentally during daytime, in the street as a
      result of falls and road traffic accidents (RTA). Significant increase of serum
      amylase, lipase and GGT levels on re-evaluation after 24 h from admission were
      demonstrated in combined head lesions. There was a high significant negative
      correlation between GCS and these enzymes both on admission and 24 h after
      admission. Serum levels of measured enzymes were significantly higher in non
      survivors as compared to survivors. CONCLUSION: Serum amylase, lipase and GGT are
      good predictors of the outcome in head injured patients. This could be useful for
      forensic experts to deduce that the poor outcome of the victims was primarily
      related to the effects of head trauma and its sequences.

PMID- 29031234
TI  - Proposal of a new radiological classification system for spinal meningiomas as a
      descriptive tool and surgical guide.
AB  - OBJECTIVES: 1) To provide neurosurgeons and radiologists with a new quantitative
      and anatomical method to describe spinal meningiomas (SM) consistently. 2) To
      provide a guide to the surgical approach needed and amount of bony resection
      required based on the proposed classification. 3) To report the distribution of
      our 58 cases of SM over different Stages and Subtypes in correlation to the
      surgical treatment needed for each case. 4) To briefly review the literature on
      the rare non-conventional surgical corridors to resect SM. PATIENTS AND METHODS:
      We reviewed the literature to report on previously published cohorts and
      classifications used to describe the location of the tumor inside the spinal
      canal. We reviewed the cases that were published prior showing non-conventional
      surgical approaches to resect spinal meningiomas. We proposed our classification
      system composed of Staging based on maximal cross-sectional surface area of tumor
      inside canal, Typing based on number of quadrants occupied by tumor and Subtyping
      based on location of the tumor bulk to spinal cord. Extradural and extra-spinal
      growth were also covered by our classification. We then applied it
      retrospectively on our 58 cases. RESULTS: 12 articles were published illustrating
      overlapping terms to describe spinal meningiomas. Another 7 articles were
      published reporting on 23 cases of anteriorly located spinal meningiomas treated
      with approaches other than laminectomies/laminoplasties. 4 Types, 9 Subtypes and
      4 Stages were described in our Classification System. In our series of 58
      patients, no midline anterior type was represented. Therefore, all our cases were
      treated by laminectomies or laminoplasties (with/without facetectomies) except a
      case with a paraspinal component where a costotransversectomy was needed.
      CONCLUSION: Spinal meningiomas can be radiologically described in a precise
      fashion. Selection of surgical corridor depends mainly on location of tumor bulk
      inside canal.

PMID- 29031235
TI  - Homeobox genes and tooth development: Understanding the biological pathways and
      applications in regenerative dental science.
AB  - OBJECTIVES: Homeobox genes are a group of conserved class of transcription
      factors that function as key regulators during the embryonic developmental
      processes. They act as master regulator for developmental genes, which involves
      coordinated actions of various auto and cross-regulatory mechanisms. In this
      review, we summarize the expression pattern of homeobox genes in relation to the
      tooth development and various signaling pathways or molecules contributing to the
      specific actions of these genes in the regulation of odontogenesis. MATERIALS AND
      METHODS: An electronic search was undertaken using combination of keywords e.g.
      Homeobox genes, tooth development, dental diseases, stem cells, induced
      pluripotent stem cells, gene control region was used as search terms in PubMed
      and Web of Science and relevant full text articles and abstract were retrieved
      that were written in English. A manual hand search in text books were also
      carried out. Articles related to homeobox genes in dentistry and tissue
      engineering and regenerative medicine of odontogenesis were selected. RESULTS:
      The possible perspective of stem cells technology in odontogenesis and subsequent
      analysis of gene correction pertaining to dental disorders through the
      possibility of induced pluripotent stem cells technology is also inferred.
      CONCLUSIONS: We demonstrate the promising role of tissue engineering and
      regenerative medicine on odontogenesis, which can generate a new ray of hope in
      the field of dental science.

PMID- 29031236
TI  - Inhibitory effect of probiotic lactobacilli supernatants on single and mixed non
      albicans Candida species biofilm.
AB  - OBJECTIVES: Oral candidiasis is one of the most common human fungal infections.
      While most cases of the Candida species isolated from the oral cavity are Candida
      albicans, a large number of candidiasis is attributed to non-albicans Candida
      species. In this study, we aim to evaluate the in vitro inhibition of
      supernatants of Lactobacillus gasseri and Lactobacillus rhamnosus on the single
      and mixed species biofilm of non-albicans Candida species, including Candida
      tropicalis, Candida krusei and Candida parapsilosis. DESIGN: Cell-free
      supernatants of Lactobacillus gasseri and Lactobacillus rhamnosus were prepared.
      Single and mixed non-albicans Candida species biofilm were formed in the 96-well
      microplate and on the surfaces of medical grade silicone. Biomass and cell
      viability were tested with crystal violet and cell counting kit-8. In order to
      examine the ability of the supernatant to disrupt pre-formed biofilm, supernatant
      was added to 24h-old biofilms. Biofilm architecture on silicone was investigated
      by scanning electron microscopy and confocal laser scanning microscopy was used
      to examine live/dead organisms within biofilm. RESULTS: Single and mixed species
      biofilms and cell viability of non-albicans Candida biofilms were inhibited by
      probiotic lactobacilli supernatants. Matrue biofilm formation was disrupted by
      lactobacilli supernatants added at 24h after biofilm initiation. Examination with
      confocal laser scanning microscopy and scanning electron microscopy confirmed
      that lactobacilli supernatants inhibited the mixed biofilms and damaged the
      cells. CONCLUSIONS: Our data elucidate the inhibitory activity of probiotic
      lactobacilli on non-albicans Candida biofilm, so as to support their utility as
      an adjunctive therapeutic mode against oral candida infections.

PMID- 29031237
TI  - Novel methodology for determining the effect of adsorbates on human enamel acid
      dissolution.
AB  - OBJECTIVE: The effect of various interventions on enamel demineralisation can be
      determined by chemically measuring mineral ions dissolved by the attacking acid.
      Results are usually expressed as mineral loss per surface area of enamel exposed.
      Acid resistant varnish or adhesive tape are typically used to delineate an area
      of enamel. However, enamel surface curvature, rugosity and porosity reduce the
      reliability of simple area measurements made at the macro scale. Our aim was to
      develop a simple method for investigating the effect of adsorbates on enamel
      demineralisation that does not rely on knowing the area of enamel exposed. As an
      exemplar we have used salivary proteins as a model adsorbate. DESIGN: Natural
      human tooth enamel surfaces were subjected to five sequential acid challenges and
      then incubated in adsorbate (whole clarified saliva) followed by a further 15
      acid challenges. Demineralisation was determined by measuring the phosphate
      released into the acid during each exposure by a spectrophotometric assay. The
      initial five challenges established a mean baseline mineral loss for each tooth
      against which the effect of subsequently adsorbed proteins could be compared.
      RESULTS: Salivary proteins significantly reduced the acid demineralisation of
      human enamel by 43% (p<0.01). Loss of proteins during each challenge corresponded
      to a gradual reduction in the degree of protection afforded. CONCLUSIONS: The
      methodology provides a simple and flexible means to investigate the effect of any
      adsorbate on enamel acid dissolution. Knowledge of the area of exposed enamel is
      irrelevant as each tooth acts as its own negative control.

PMID- 29031238
TI  - The effect of supragingival biofilm re-development on the subgingival microbiota
      in chronic periodontitis.
AB  - OBJECTIVE: In this study, we hypothesized that in the absence of oral hygiene, re
      growth of the climax microbial communities of supra and subgingival biofilm
      happens in a faster and more intense fashion in individuals with chronic
      periodontitis (CP) compared to periodontally healthy controls (PH). DESIGN:
      Thirty patients (PH=15 and CP=15) received professional supragingival
      prophylaxis, and were asked to refrain from oral hygiene for 7days. Supra and
      subgingival biofilm samples and GCF were collected from randomly selected
      quadrants at baseline (before prophylaxis), immediately after prophylaxis, 2h,
      6h, 24h, and 7days after prophylaxis. The composition of the biofilm was
      determined by the checkerboard method. RESULTS: All subjects developed gingivitis
      at the end of 7days without oral hygiene. GCF mean volumes were significantly
      higher in CP than PH patients at baseline, but they started decreasing 2h after
      prophylaxis, returning to baseline levels after 24h in both groups. Significant
      increases in mean counts for most of the species evaluated were observed in both
      groups and biofilms over time (p<0.05). Few hours after prophylaxis, a more
      marked reduction in microbial counts happened in the supragingival biofilm of the
      CP group, and re-development of biofilm started later than in the PH group. At
      7days, no differences were seen between groups. Significant differences in
      kinetics of re-colonization between groups were observed only in the subgingival
      biofilm for T. denticola and F. nucleatum ss vicentii (increased in the CP), and
      N. mucosa (increased in the PH group; p<0.05). CONCLUSIONS: Biofilm re
      development was very similar between CP and PH individuals, although microbial re
      growth occurred few hours earlier in PH than PC. Only 3 species in the
      subgingival biofilm differed in re-colonization between groups. Thus, we reject
      the hypothesis that re-colonization of biofilm in CP patients is more intense and
      faster than in individuals with PH.

PMID- 29031239
TI  - Probiotic intervention influences the salivary levels of Matrix Metalloproteinase
      (MMP)-9 and Tissue Inhibitor of metalloproteinases (TIMP)-1 in healthy adults.
AB  - OBJECTIVE: To study the effect of orally administered Bifidobacterium animalis
      subsp. lactis BB-12 and Lactobacillus rhamnosus GG on the salivary levels of
      Matrix Metalloproteinases (MMP)-8, MMP-9 and of Tissue Inhibitor of
      Metalloproteinases (TIMP)-1 in healthy adults. Furthermore, the correlations
      between MMP-8, MMP-9 and TIMP-1 and plaque and gingival indices, salivary mutans
      streptococci and lactobacilli counts, and stimulated saliva secretion rate were
      analysed. DESIGN: The salivary samples originated from a randomized controlled
      trial where healthy student volunteers consumed probiotic or placebo lozenges
      twice a day for four weeks. The saliva samples were collected and clinical
      parameters measured at the baseline and at the end of the original study. For
      this study, the salivary levels of MMP-8, MMP-9 and TIMP-1 were analysed with
      immunofluorometric assay (IFMA) and enzyme-linked immunosorbent assay (ELISA).
      RESULTS: In the probiotic group (n=29), salivary MMP-9 levels increased (p<0.01)
      and TIMP-1 levels decreased (p<0.01) significantly during the intervention.
      Furthermore, MMP-9/TIMP-1 ratio differed significantly from the baseline level
      (p<0.01). These changes were not observed in the control group (n=31). In the
      whole data, salivary MMP-9 and gingival index correlated (r=0.260, p<0.05 at
      baseline and r=0.354, p<0.01 at the end of the study). Intergroup differences or
      correlations with other clinical parameters were not found. Probiotic consumption
      did not affect the saliva flow rate. CONCLUSIONS: Increased MMP-9 and decreased
      TIMP-1 levels in saliva may indicate that probiotics have immunomodulatory
      effects in the oral cavity. Furthermore, increased salivary MMP-9 levels may be
      an indication of the defensive potential of matrix metalloproteinases.

PMID- 29031240
TI  - Colonization of oropharynx and lower respiratory tract in critical patients: Risk
      of ventilator-associated pneumonia.
AB  - OBJECTIVE: To investigate the microbial diversity existing in oral cavity and
      respiratory tract samples (from mini-bronchoalveolar lavage (BAL), endotracheal
      aspirate, and orotracheal tube) of patients on mechanical ventilation by using
      the checkerboard DNA-DNA hybridisation. Also, the study aimed to evaluate whether
      the microbial profile in the oral cavity is found in respiratory tract samples,
      at different periods of mechanical ventilation time (12h, 48h, 96h) in attempt to
      identification of relationship between VAP (ventilator-associated pneumonia) and
      bacterial species studied. The last objective was to analyses correlation between
      blood cultures and VAP. DESIGN: The samples were collected from ten patients in
      intensive care unit with medical prescription of orotracheal intubation and
      mechanical ventilation. Clinical data were tabulated and blood cultures were
      performed according medical indication. For checkerboard samples collection,
      chosen sites were the dorsal side of the tongue and gingival sulcus at 12h, 48h,
      96h, BAL, at 12h, endotracheal aspirate at 48 and 96h, and orotracheal tube at
      extubation time, when feasible. RESULTS: It was possible to identify the presence
      of bacterial species in mouth and in the BAL/endotracheal aspirate. The data
      demonstrated an increase in the quantity of bacterial associated with prolonged
      use of mechanical ventilation (48 and 96h). CONCLUSIONS: Bacterial species may
      migrate rapidly from mouth and upper airways during orotracheal intubation which
      contributes to the pathogenesis of VAP. There were associations between VAP and
      Enterococcus faecalis, Fusobacterium periodonticum, Gemella morbillorum,
      Neisseria mucosa, Propionibacterium acnes, Prevotella melaninogenica,
      Streptococcus oralis, Streptococcus sanguinis, Treponema denticola, Treponema
      socransckii, and Veillonella parvula.

PMID- 29031241
TI  - Citrus pectin attenuates endotoxin shock via suppression of Toll-like receptor
      signaling in Peyer's patch myeloid cells.
AB  - Pectin, a water-soluble dietary fiber, has been found to improve survival in
      endotoxin shock. However, the underlying mechanism by which pectin exerts its
      protective effect against endotoxin shock remains unknown. Apart from its
      prebiotic effects, it has been suggested that pectin directly affects immune
      cells to regulate inflammatory responses. In this study, we investigated the
      direct effect of pectin in murine model of endotoxin shock. Citrus pectin
      solution was administered to male C57BL/6 mice for 10 days. Thereafter,
      hypothermia was induced in the mice with intraperitoneal injection of
      lipopolysaccharide (LPS). The pectin-treated mice showed attenuation of both the
      decrease in rectal temperature and increase in serum IL-6 level as compared to
      vehicle control mice. Simultaneously, the pectin-treated mice showed reduced
      levels of inflammatory cytokine mRNA in Peyer's patches and mesenteric lymph
      nodes, but not in the spleen. Peyer's patch cells from the pectin-treated mice
      were sorted and their levels of IL-6 production on LPS stimulation were measured.
      The results of ex vivo analysis indicated that IL-6 secretion from CD11c+ cells
      was suppressed by oral administration of pectin. Furthermore, IL-6 secretion from
      Toll-like receptor (TLR)-activated RAW264.7 cells was suppressed by pretreatment
      with pectin in vitro. This suppression was observed even with degraded pectin
      pretreatment but not with polygalacturonic acid, as the principal constituent of
      the pectin backbone. Taken together, these results suggest that pectin intake
      suppresses TLR-induced inflammatory cytokine expression in Peyer's patch myeloid
      cells, presumably through inhibition of TLR signaling by the pectin side chains.

PMID- 29031242
TI  - Dietary creatine supplementation lowers hepatic triacylglycerol by increasing
      lipoprotein secretion in rats fed high-fat diet.
AB  - Recent studies have shown that dietary creatine supplementation can prevent lipid
      accumulation in the liver. Creatine is a small molecule that plays a large role
      in energy metabolism, but since the enzyme creatine kinase is not present in the
      liver, the classical role in energy metabolism does not hold in this tissue. Fat
      accumulation in the liver can lead to the development of nonalcoholic fatty liver
      disease (NAFLD), a progressive disease that is prevalent in humans. We have
      previously reported that creatine can directly influence lipid metabolism in cell
      culture to promote lipid secretion and oxidation. Our goal in the current study
      was to determine whether similar mechanisms that occur in cell culture were
      present in vivo. We also sought to determine whether dietary creatine
      supplementation could be effective in reversing steatosis. Sprague-Dawley rats
      were fed a high-fat diet or a high-fat diet supplemented with creatine for 5
      weeks. We found that rats supplemented with creatine had significantly improved
      rates of lipoprotein secretion and alterations in mitochondrial function that
      were consistent with greater oxidative capacity. We also find that introducing
      creatine into a high-fat diet halted hepatic lipid accumulation in rats with
      fatty liver. Our results support our previous report that liver cells in culture
      with creatine secrete and oxidize more oleic acid, demonstrating that dietary
      creatine can effectively change hepatic lipid metabolism by increasing
      lipoprotein secretion and oxidation in vivo. Our data suggest that creatine might
      be an effective therapy for NAFLD.

PMID- 29031243
TI  - Preparation and Evaluation of Rifampicin and Co-trimoxazole-loaded Nanocarrier
      against Brucella melitensis Infection
AB  - Background: Brucellosis or Malta fever is a contagious infection common between
      human and domestic animals. Many antibiotics are used for brucellosis treatment,
      but they are not efficient and put heavy burden on society. Co-trimoxazole and
      rifampicin are two candidates for brucellosis treatment. In this study, we aimed
      to enhance the efficacy of these antibiotics using designed nanoparticles.
      Methods: Different concentrations of co-trimoxazole and rifampicin were used for
      loading onto a nanostructure of synthesized monomethoxy poly(ethylene glycol)
      oleate (mPEG-OA). The solubility, cytotoxicity, and efficacy of these nano-packed
      antibiotics on Brucella-infected murine phagocytic cells were examined, as
      compared with free antibiotics. Then the release  nanoparticles was increased
      approximately 3.5 and 1.5fold, respectively, which is considerable in comparison
      with free insoluble ones. Results: Despite acceptable loading percentage, the
      application of co-trimoxazole-loaded nanoparticle on Brucella-infected J774A.1
      murine macrophage-like cells did not lead to reduction in the number of bacteria;
      however, the efficacy of rifampicin on Brucella-infected murine phagocytic cells
      enhanced. Conclusion: In the current study, the efficacy of rifampicin on
      reducing the number of Brucella melitensis increased by the novel synthesized
      nanostructure. In contrast, since co-trimoxazole efficacy did not enhance by
      loading onto nanoparticles, the co-trimoxazole inefficiency is most likely not
      due to its low penetration or insolubility, and probably there are other factors
      that remain to be clarified in the future investigations.

PMID- 29031244
TI  - Development of New Recombinant DgK Antigen for Diagnosis of Dirofilaria immitis
      Infections in Dogs Using ELISA Technique and Its Comparison to Molecular Methods
AB  - Background: Dirofilaria immitis is a cosmopolitan zoonotic, vector-borne parasite
      of carnivorous animals causing dirofilariasis in human beings. Common commercial
      serodiagnostic tests for canine dirofilariasis usually lead to different results
      in their sensitivity and specificity. The present study reports development of
      recombinant DgK (rDgK) antigen of D. immitis for accurate immunodiagnosis of D.
      Immitis-infected dogs using indirect ELISA test. Methods: The rDgK coding
      sequence was successfully sequenced, codon optimized and cloned into pET-24a(+)
      expression vector and then expressed in Escherichia coli. The recombinant DgK was
      affinity purified using Ni2+-charged HiTrap chelating column, followed by testing
      in Western blotting and enzyme-linked immunosorbent assays (ELISA) with dog sera
      from a dirofilariasis endemic area. The performance of rDgK ELISA was evaluated
      using 60 sera collected from suspected dogs, while molecular technique was used
      as a reference test. Results: Sera from positive control D. immitis infection
      produced a strong IgG antibody response to rDgK both in ELISA and Western
      blotting tests. The sensitivity and specificity related to diagnostic potential
      of rDgK for ELISA were 92.5% and 87.5%, respectively. The results of rDgK ELISA
      showed a high agreement (0.764) with molecular identification. Conclusion: The
      findings revealed that the developed new rDgK antigen is sensitive and specific
      for immunodiagnosis of canine dirofilariasis using ELISA test.

PMID- 29031245
TI  - Decrease in Cavity Size and Oligodendrocyte Cell Death Using Neurosphere-Derived
      Oligodendrocyte-Like Cells in Spinal Cord Contusion Model
AB  - Background: Oligodendrocyte cell death is among the important features of spinal
      cord injury, which appears within 15 min and occurs intensely for 4 h after
      injury, in the rat spinal contusion model. Accordingly, the number of
      oligodendrocytes progressively reduced within 24 h after injury. Administration
      of oligodendrocyte-like cells (OLCs) into the lesion area is one of the
      approaches to counterbalance this condition. Methods: Bone marrow stromal cells
      were transdifferentiated into neurospheres and then into neural stem cells and
      later were differentiated into OLCs using triiodothyronine and transplanted into
      the spinal cord contusion rats. The post-injury functional recovery was explored
      and compared with the control group using Basso-Beattie-Bresnahan and narrow beam
      behavioral tests. At the end of 12th week, spinal cord segments T12-L1 were
      histomorphologically studied by immunohistochemistry. Results: Motor improvement
      was more obvious during 2nd to 4th weeks and got less prominent during 4th to
      12th weeks. Histomorphometric findings indicated that cavity formation decreased
      in epicenter of transplantation area in experimental groups in comparison with
      the control groups. Conclusion: The findings obtained in the present study showed
      that OLC therapy is a potential approach in the treatment of spinal cord
      traumatic injuries.

PMID- 29031246
TI  - Structural evolution and atomic dynamics in Ni-Nb metallic glasses: A molecular
      dynamics study.
AB  - The composition and temperature dependence of static and dynamic structures in
      NixNb1-x (x = 50-70 at. %) were systematically studied using molecular dynamics
      with a new-released semi-empirical embedded atom method potential by Mendelev.
      The calculated pair correlation functions and the structure factor match well
      with the experimental data, demonstrating the reliability of the potential within
      relatively wide composition and temperature ranges. The local atomic structures
      were then characterized by bond angle distributions and Voronoi tessellation
      methods, demonstrating that the icosahedral ?0,0,12,0? is only a small fraction
      in the liquid state but increases significantly during cooling and becomes
      dominant at 300 K. The most abundant clusters are identified as ?0,0,12,0? and
      distorted icosahedron ?0,2,8,2?. The large fraction of these two clusters hints
      that the relatively good glass forming ability is near the eutectic point. Unlike
      Cu-Zr alloys, both the self-diffusion coefficient and shear viscosity are
      insensitive to compositions upon cooling in Ni-Nb alloys. The breakdown of the
      Stokes-Einstein relation happens at around 1.6Tg (Tg: glass transition
      temperature). In the amorphous state, the solid and liquid-like atoms can be
      distinguished based on the Debye-Waller factor ?u2?. The insensitivity of the
      dynamic properties of Ni-Nb alloys to compositions may result from the relatively
      simple solidification process in the phase diagram, in which only one eutectic
      point exists in the studied composition range.

PMID- 29031247
TI  - Extracting spectroscopic molecular parameters from short pulse photo-electron
      angular distributions.
AB  - Using a quantum wave packet simulation including the nuclear and electronic
      degrees of freedom, we investigate the femtosecond and picosecond energy- and
      angle-resolved photoelectron spectra of the E(Sigmag+1) electronic state of Li2.
      We find that the angular distributions of the emitted photoelectrons depend
      strongly on the pulse duration in the regime of ultrashort laser pulses. This
      effect is illustrated by the extraction of a time-dependent asymmetry parameter
      whose variation with pulse duration can be explained by an incoherent average
      over different ion rotational quantum numbers. We then derive for the variation
      of the asymmetry parameter a simple analytical formula, which can be used to
      extract the asymptotic CW asymmetry parameters of individual transitions from
      measurements performed with ultra-short pulses.

PMID- 29031248
TI  - Characterizing and optimizing a laser-desorption molecular beam source.
AB  - The design and characterization of a new laser-desorption molecular beam source,
      tailored for use in x-ray free-electron laser and ultrashort-pulse laser imaging
      experiments, is presented. It consists of a single mechanical unit containing all
      source components, including the molecular-beam valve, the sample, and the fiber
      coupled desorption laser, which is movable in five axes, as required for
      experiments at central facilities. Utilizing strong-field ionization, we
      characterize the produced molecular beam and evaluate the influence of desorption
      laser pulse energy, relative timing of valve opening and desorption laser, sample
      bar height, and which part of the molecular packet is probed on the sample
      properties. Strong-field ionization acts as a universal probe and allows
      detecting all species present in the molecular beam, and hence enables us to
      analyze the purity of the produced molecular beam, including molecular fragments.
      We present optimized experimental parameters for the production of the purest
      molecular beam, containing the highest yield of intact parent ions, which we find
      to be very sensitive to the placement of the desorbed-molecule plumes within the
      supersonic expansion.

PMID- 29031249
TI  - Communication: Programmable self-assembly of thin-shell mesostructures.
AB  - We study numerically the possibility of programmable self-assembly of various
      thin-shell architectures. They include clusters isomorphic to fullerenes C20 and
      C60, finite and infinite sheets, tube-shaped and toroidal mesostructures. Our
      approach is based on the recently introduced directionally functionalized
      nanoparticle platform, for which we employ a hybrid technique of Brownian
      dynamics with stochastic bond formation. By combining a number of strategies, we
      were able to achieve a near-perfect yield of the desired structures with a
      reduced "alphabet" of building blocks. Among those strategies are the following:
      the use of bending rigidity of the interparticle bond as a control parameter,
      programming the morphology with a seed architecture, use of chirality-preserving
      symmetries for reduction of the particle alphabet, and the hierarchic approach.

PMID- 29031250
TI  - Communication: Relaxation-limited electronic currents in extended reservoir
      simulations.
AB  - Open-system approaches are gaining traction in the simulation of charge transport
      in nanoscale and molecular electronic devices. In particular, "extended
      reservoir" simulations, where explicit reservoir degrees of freedom are present,
      allow for the computation of both real-time and steady-state properties but
      require relaxation of the extended reservoirs. The strength of this relaxation,
      gamma, influences the conductance, giving rise to a "turnover" behavior analogous
      to Kramers turnover in chemical reaction rates. We derive explicit, general
      expressions for the weak and strong relaxation limits. For weak relaxation, the
      conductance increases linearly with gamma and every electronic state of the total
      explicit system contributes to the electronic current according to its "reduced"
      weight in the two extended reservoir regions. Essentially, this represents two
      conductors in series-one at each interface with the implicit reservoirs that
      provide the relaxation. For strong relaxation, a "dual" expression-one with the
      same functional form-results, except now proportional to 1/gamma and dependent on
      the system of interest's electronic states, reflecting that the strong relaxation
      is localizing electrons in the extended reservoirs. Higher order behavior (e.g.,
      gamma2 or 1/gamma2) can occur when there is a gap in the frequency spectrum.
      Moreover, inhomogeneity in the frequency spacing can give rise to a pseudo
      plateau regime. These findings yield a physically motivated approach to
      diagnosing numerical simulations and understanding the influence of relaxation,
      and we examine their occurrence in both simple models and a realistic,
      fluctuating graphene nanoribbon.

PMID- 29031251
TI  - Distance-including rigorous upper bounds and tight estimates for two-electron
      integrals over long- and short-range operators.
AB  - We introduce both rigorous and non-rigorous distance-dependent integral estimates
      for four-center two-electron integrals derived from a distance-including Schwarz
      type inequality. The estimates are even easier to implement than our so far most
      efficient distance-dependent estimates [S. A. Maurer et al., J. Chem. Phys. 136,
      144107 (2012)] and, in addition, do not require well-separated charge
      distributions. They are also applicable to a wide range of two-electron operators
      such as those found in explicitly correlated theories and in short-range hybrid
      density functionals. For two such operators with exponential distance decay [e
      r12 and erfc(0.11?r12)/r12], the rigorous bound is shown to be much tighter than
      the standard Schwarz estimate with virtually no error penalty. The non-rigorous
      estimate gives results very close to an exact screening for these operators and
      for the long-range 1/r12 operator, with errors that are completely controllable
      through the integral screening threshold. In addition, we present an alternative
      form of our non-rigorous bound that is particularly well-suited for improving the
      PreLinK method [J. Kussmann and C. Ochsenfeld, J. Chem. Phys. 138, 134114 (2013)]
      in the context of short-range exchange calculations.

PMID- 29031252
TI  - Reorientation-induced spectral diffusion of non-isotropic orientation
      distributions.
AB  - When reorientation of a vibrational chromophore is faster than the relaxation of
      its local environment, the frequency fluctuation correlation function (FFCF)
      measured by two-dimensional infrared spectroscopy (2D-IR) spectroscopy is an
      interplay of scalar structural spectral diffusion and vectorial reorientation
      induced spectral diffusion (RISD). Theory has been established to calculate the
      RISD component of different polarization configurations with the assumption that
      the molecule orients randomly in a local electric field. We show here that in the
      [BMIM][SCN]/AOT/chlorobenzene system, where the local electric field is strong,
      this assumption is incapable of reproducing the experimental results. We modify
      the current theory by assuming a Boltzmann distribution of transition dipoles of
      the chromophores in a local electric field and use a Markov chain model to
      calculate the RISD component of 2D-IR with different polarization configurations.
      The result reproduces key features of the experiment and suggests a potential ion
      exchange in the [BMIM][SCN]/AOT/chlorobenzene system.

PMID- 29031253
TI  - Controlling the crystal polymorph by exploiting the time dependence of nucleation
      rates.
AB  - Most substances can crystallise into two or more different crystal lattices
      called polymorphs. Despite this, there are no systems in which we can
      quantitatively predict the probability of one competing polymorph forming instead
      of the other. We address this problem using large scale (hundreds of events)
      studies of the competing nucleation of the alpha and gamma polymorphs of glycine.
      In situ Raman spectroscopy is used to identify the polymorph of each crystal. We
      find that the nucleation kinetics of the two polymorphs is very different.
      Nucleation of the alpha polymorph starts off slowly but accelerates, while
      nucleation of the gamma polymorph starts off fast but then slows. We exploit this
      difference to increase the purity with which we obtain the gamma polymorph by a
      factor of ten. The statistics of the nucleation of crystals is analogous to that
      of human mortality, and using a result from medical statistics, we show that
      conventional nucleation data can say nothing about what, if any, are the
      correlations between competing nucleation processes. Thus we can show that with
      data of our form it is impossible to disentangle the competing nucleation
      processes. We also find that the growth rate and the shape of a crystal depend on
      it when nucleated. This is new evidence that nucleation and growth are linked.

PMID- 29031254
TI  - Premelting, solid-fluid equilibria, and thermodynamic properties in the high
      density region based on the Lennard-Jones potential.
AB  - The Lennard-Jones potential is used to study the high density fluid and face
      centered cubic solid state region, including solid-fluid equilibria. Numerous
      thermodynamic properties are considered, elucidating the behavior of matter in
      this poorly studied region. The present molecular simulation results are
      extensively compared to the latest and most accurate equation of state models for
      fluid and solid phases. It is shown that current models do not cover the
      thermodynamics of the system adequately near the solid-fluid phase transition.
      Furthermore, thermodynamic stability is analyzed, indicating that published solid
      fluid coexistence data may not be correct at high temperatures. Particular
      attention is paid to the premelting zone, a range of states close to the melting
      line, which is characterized by strong variations of several thermodynamic
      properties. Because the underlying microscopic mechanisms are not yet fully
      understood, it is hoped that these data may contribute to the development of a
      theoretical framework for describing premelting effects.

PMID- 29031255
TI  - Compressed representation of dispersion interactions and long-range electronic
      correlations.
AB  - The description of electron correlation in quantum chemistry often relies on
      multi-index quantities. Here, we examine a compressed representation of the long
      range part of electron correlation that is associated with dispersion
      interactions. For this purpose, we perform coupled-cluster singles and doubles
      (CCSD) computations on localized orbitals, and then extract the portion of CCSD
      amplitudes corresponding to dispersion energies. Using singular value
      decomposition, we uncover that a very compressed representation of the amplitudes
      is possible in terms of occupied-virtual geminal pairs located on each monomer.
      These geminals provide an accurate description of dispersion energies at medium
      and long distances. The corresponding virtual orbitals are examined by further
      singular value decompositions of the geminals. We connect each component of the
      virtual space to the multipole expansion of dispersion energies. Our results are
      robust with respect to basis set change and hold for systems as large as the
      benzene-methane dimer. This compressed representation of dispersion energies
      paves the way to practical and accurate approximations for dispersion, for
      example, in local correlation methods.

PMID- 29031256
TI  - Formic acid aggregation in 2D supersonic expansions probed by FTIR imaging.
AB  - C=O stretching vibrations of formic acid trimers are assigned on the basis of
      FTIR and Raman jet spectroscopy and further validated by an FTIR imaging study
      based on their aggregation behavior in supersonic expansions. The effect of shock
      waves on cluster formation and decomposition is probed by shifting them into the
      field of view of the focal plane array detector. A double slit nozzle is
      presented that merges two supersonic jets for a more localized study of such
      shock waves.

PMID- 29031258
TI  - Ultrafast and nonlinear spectroscopy of brilliant green-based nanoGUMBOS with
      enhanced near-infrared emission.
AB  - The synthesis, characterization, ultrafast dynamics, and nonlinear spectroscopy
      of 30 nm nanospheres of brilliant green-bis(pentafluoroethylsulfonyl)imide
      ([BG][BETI]) in water are reported. These thermally stable nanoparticles are
      derived from a group of uniform materials based on organic salts (nanoGUMBOS)
      that exhibit enhanced near-infrared emission compared with the molecular dye in
      water. The examination of ultrafast transient absorption spectroscopy results
      reveals that the overall excited-state relaxation lifetimes of [BG][BETI]
      nanoGUMBOS are longer than the brilliant green molecular dye in water due to
      steric hindrance of the torsional degrees of freedom of the phenyl rings around
      the central carbon. Furthermore, the second harmonic generation signal of
      [BG][BETI] nanoGUMBOS is enhanced by approximately 7 times and 23 times as
      compared with colloidal gold nanoparticles of the same size and the brilliant
      green molecular dye in water, respectively. A very clear third harmonic
      generation signal is observed from the [BG][BETI] nanoGUMBOS but not from either
      the molecular dye or the gold nanoparticles. Overall, these results show that
      [BG][BETI] nanoGUMBOS exhibit altered ultrafast and nonlinear spectroscopy that
      is beneficial for various applications including nonlinear imaging probes,
      biomedical imaging, and molecular sensing.

PMID- 29031257
TI  - The effects of halogen elements on the opening of an icosahedral B12 framework.
AB  - The fully halogenated or hydrogenated B12X122- (X = H, F, Cl, Br and I) clusters
      are confirmed to be icosahedral. On the other hand, the bare B12 cluster is shown
      to have a planar structure. A previous study showed that a transformation from an
      icosahedron to a plane happens when 5 to 7 iodine atoms are remained [P. Farras
      et al., Chem. - Eur. J. 18, 13208-13212 (2012)]. Later, the transition was
      confirmed to be seven iodine atoms based on an infrared spectroscopy study [M. R.
      Fagiania et al., Chem. Phys. Lett. 625, 48-52 (2015)]. In this study, we
      investigated the effects of different halogen atoms on the opening of the B12
      icosahedral cage by means of density functional theory calculations. We found
      that the halogen elements do not have significant effects on the geometries of
      the clusters. The computed infrared (IR) spectra show similar representative
      peaks for all halogen doped clusters. Interestingly, we found a blue-shift in the
      IR spectra with the increase in the mass of the halogen atoms. Further, we
      compared the Gibbs free energies at different temperatures for different halogen
      atoms. The results show that the Gibbs free energy differences between open and
      close structures of B12X7- become larger when heavier halogen atoms are
      presented. This interesting finding was subsequently investigated by the energy
      decomposition analysis.

PMID- 29031259
TI  - An intrinsic representation of atomic structure: From clusters to periodic
      systems.
AB  - We have improved our distance matrix and eigen-subspace projection function (EPF)
      [X.-T. Li et al., J. Chem. Phys. 146, 154108 (2017)] to describe the atomic
      structure for periodic systems. Depicting the local structure of an atom, the EPF
      turns out to be invariant with respect to the choices of the unit cell and
      coordinate frame, leading to an intrinsic representation of the crystal with a
      set of EPFs of the nontrivial atoms. The difference of EPFs reveals the
      difference of atoms in local structure, while the accumulated difference between
      two sets of EPFs can be taken as the distance between configurations. Exemplified
      with the cases of carbon allotropes and boron sheets, our EPF approach shows
      exceptional rationality and efficiency to distinguish the atomic structures,
      which is crucial in structure recognition, comparison, and analysis.

PMID- 29031260
TI  - Aggregation of flexible polyelectrolytes: Phase diagram and dynamics.
AB  - Similarly charged polymers in solution, known as polyelectrolytes, are known to
      form aggregated structures in the presence of oppositely charged counterions.
      Understanding the dependence of the equilibrium phases and the dynamics of the
      process of aggregation on parameters such as backbone flexibility and charge
      density of such polymers is crucial for insights into various biological
      processes which involve biological polyelectrolytes such as protein, DNA, etc.
      Here, we use large-scale coarse-grained molecular dynamics simulations to obtain
      the phase diagram of the aggregated structures of flexible charged polymers and
      characterize the morphology of the aggregates as well as the aggregation
      dynamics, in the presence of trivalent counterions. Three different phases are
      observed depending on the charge density: no aggregation, a finite bundle phase
      where multiple small aggregates coexist with a large aggregate and a fully phase
      separated phase. We show that the flexibility of the polymer backbone causes
      strong entanglement between charged polymers leading to additional time scales in
      the aggregation process. Such slowing down of the aggregation dynamics results in
      the exponent, characterizing the power law decay of the number of aggregates with
      time, to be dependent on the charge density of the polymers. These results are
      contrary to those obtained for rigid polyelectrolytes, emphasizing the role of
      backbone flexibility.

PMID- 29031261
TI  - A study of accurate exchange-correlation functionals through adiabatic
      connection.
AB  - A systematic way of improving exchange-correlation energy functionals of density
      functional theory has been to make them satisfy more and more exact relations.
      Starting from the initial generalized gradient approximation (GGA) functionals,
      this has culminated into the recently proposed SCAN (strongly constrained and
      appropriately normed) functional that satisfies several known constraints and is
      appropriately normed. The ultimate test for the functionals developed is the
      accuracy of energy calculated by employing them. In this paper, we test these
      exchange-correlation functionals-the GGA hybrid functionals B3LYP and PBE0 and
      the meta-GGA functional SCAN-from a different perspective. We study how
      accurately these functionals reproduce the exchange-correlation energy when
      electron-electron interaction is scaled as alphaVee with alpha varying between 0
      and 1. Our study reveals interesting comparison between these functionals and the
      associated difference Tc between the interacting and the non-interacting kinetic
      energy for the same density.

PMID- 29031262
TI  - Communication: General variational approach to nuclear-quadrupole coupling in
      rovibrational spectra of polyatomic molecules.
AB  - A general algorithm for computing the quadrupole-hyperfine effects in the
      rovibrational spectra of polyatomic molecules is presented for the case of
      ammonia (NH3). The method extends the general variational approach TROVE [J. Mol.
      Spectrosc. 245, 126-140 (2007)] by adding the extra term in the Hamiltonian that
      describes the nuclear quadrupole coupling, with no inherent limitation on the
      number of quadrupolar nuclei in a molecule. We applied the new approach to
      compute the nitrogen-nuclear-quadrupole hyperfine structure in the rovibrational
      spectrum of NH314. These results agree very well with recent experimental
      spectroscopic data for the pure rotational transitions in the ground vibrational
      and nu2 states and the rovibrational transitions in the nu1, nu3, 2nu4, and nu1 +
      nu3 bands. The computed hyperfine-resolved rovibrational spectrum of ammonia will
      be beneficial for the assignment of experimental rovibrational spectra, further
      detection of ammonia in interstellar space, and studies of the proton-to-electron
      mass variation.

PMID- 29031263
TI  - 2D IR spectroscopy of high-pressure phases of ice.
AB  - We present experimental and simulated 2D IR spectra of some high-pressure forms
      of isotope-pure D2O ice and compare the results to those of ice Ih published
      previously [F. Perakis and P. Hamm, Phys. Chem. Chem. Phys. 14, 6250 (2012); L.
      Shi et al., ibid. 18, 3772 (2016)]. Ice II, ice V, and ice XIII have been chosen
      for this study, since this selection covers many aspects of the polymorphism of
      ice. That is, ice II is a hydrogen-ordered phase of ice, in contrast to ice Ih,
      while ice V and ice XIII are a hydrogen-disordered/ordered couple that shares
      essentially the same oxygen structure and hydrogen-bonded network. For the
      transmission 2D IR spectroscopy, a novel method had to be developed for the
      preparation of ultrathin films (1-2 MUm) of high-pressure ices with good optical
      quality. We also simulated 2D IR spectra based on molecular dynamics simulations
      connected to a vibrational exciton picture. These simulations agree with the
      experimental results in a semi-quantitative manner for ice II, while the same
      approach failed for ice V and ice XIII. From the perspective of 2D IR
      spectroscopy, ice II appears to be more inhomogeneously broadened than ice Ih,
      despite its hydrogen-order, which we attribute to the fact that ice II is
      structurally more complex with four distinguishable hydrogen bonds that mix due
      to exciton coupling. Ice V and ice XIII, on the other hand, behave as expected
      with the hydrogen-disordered case (ice V) being more inhomogenously broadened.
      Furthermore, in all hydrogen-ordered forms (ice II and ice XIII), cross peaks
      could be identified in the anisotropic 2D IR spectrum, whose signs reveal the
      relative direction of the corresponding excitonic states.

PMID- 29031264
TI  - Computing vibrational energy levels of CH4 with a Smolyak collocation method.
AB  - In this paper, we demonstrate that it is possible to apply collocation to compute
      vibrational energy levels of a five-atom molecule using an exact kinetic energy
      operator (with cross terms and coordinate-dependent coefficients). This is made
      possible by using (1) a pruned basis of products of univariate functions; (2) a
      Smolyak grid made from nested sequences of grids for each coordinate; (3) a
      collocation method that obviates the need to solve a generalized eigenvalue
      problem; (4) an efficient sequential transformation between the (nondirect
      product) grid and the (nondirect product) basis representations; and (5)
      hierarchical univariate functions that make it possible to avoid storing large
      intermediate vectors. The accuracy of the method is confirmed by computing 500
      vibrational energy levels of methane.

PMID- 29031265
TI  - Simplified expressions that incorporate finite pulse effects into coherent two
      dimensional optical spectra.
AB  - We derive general expressions that incorporate finite pulse envelope effects into
      a coherent two-dimensional optical spectroscopy (2DOS) technique. These
      expressions are simpler and less computationally intensive than the conventional
      triple integral calculations needed to simulate 2DOS spectra. The simplified
      expressions involving multiplications of arbitrary pulse spectra with 2D spectral
      response function are shown to be exactly equal to the conventional triple
      integral calculations of 2DOS spectra if the 2D spectral response functions do
      not vary with population time. With minor modifications, they are also accurate
      for 2D spectral response functions with quantum beats and exponential decay
      during population time. These conditions cover a broad range of experimental 2DOS
      spectra. For certain analytically defined pulse spectra, we also derived
      expressions of 2D spectra for arbitrary population time dependent 2DOS spectral
      response functions. Having simpler and more efficient methods to calculate
      experimentally relevant 2DOS spectra with finite pulse effect considered will be
      important in the simulation and understanding of the complex systems routinely
      being studied by using 2DOS.

PMID- 29031266
TI  - Effects of external electric field and anisotropic long-range reactivity on
      charge separation probability.
AB  - We consider the effects of external electric field and anisotropic long-range
      reactivity on the recombination dynamics of a geminate charge pair. A closed-form
      analytic expression for the ultimate separation probability of the pair is
      presented. In previous theories, analytic expressions for the separation
      probability were obtained only for the case where the recombination reaction can
      be assumed to occur at a contact separation. For this case, Noolandi and Hong
      obtained an exact solution, but their expression for the separation probability
      was too complicated to evaluate. Hence an approximate analytic expression
      proposed by Braun has been widely used. However, Braun's expression overestimates
      the separation probability when the electric field is large. In this work, we
      present an approximate analytic expression that is accurate enough for all
      parameter values. In addition, the expression is also applicable when the
      interaction between the geminate charge pair is described by screened Coulombic
      potential, and the recombination reaction has an anisotropic and long-range
      reactivity. We also provide the expression for the separation probability when
      the initial separation between the geminate charge pair is larger than the
      contact distance.

PMID- 29031267
TI  - Coherent laser-millimeter-wave interactions en route to coherent population
      transfer.
AB  - We demonstrate coherent two-photon population transfer to Rydberg states of
      barium atoms using a combination of a pulsed dye laser and a chirped-pulse
      millimeter-wave spectrometer. Numerical calculations, using a density matrix
      formalism, reproduce our experimental results and explain the factors responsible
      for the observed fractional population transferred, optimal experimental
      conditions, and possibilities for future improvements. The long coherence times
      associated with the millimeter-wave radiation aid in creating coherence between
      the ground state and Rydberg states, but higher-coherence laser sources are
      required to achieve stimulated Raman adiabatic passage and for applications to
      molecules.

PMID- 29031268
TI  - Multivalent cation induced attraction of anionic polymers by like-charged pores.
AB  - The efficiency of nanopore-based polymer sensing devices depends on the fast
      capture of anionic polyelectrolytes by negatively charged pores. This requires
      the cancellation of the electrostatic barrier associated with repulsive polymer
      pore interactions. We develop a correlation-corrected theory to show that the
      barrier experienced by the polymer can be efficiently overcome by the addition of
      multivalent cations into the electrolyte solution. Cation adsorption into the
      pore enhances the screening ability of the pore medium with respect to the bulk
      reservoir which translates into an attractive force on the polymer. Beyond a
      critical multivalent cation concentration, this correlation-induced attraction
      overcomes the electrostatic barrier and triggers the adsorption of the polymer by
      the like-charged pore. It is shown that like-charge polymer-pore attraction is
      suppressed by monovalent salt but enhanced by the membrane charge strength and
      the pore confinement. Our predictions may provide enhanced control over polymer
      motion in translocation experiments.

PMID- 29031269
TI  - Visualising crystal packing interactions in solid-state NMR: Concepts and
      applications.
AB  - In this article, we introduce and apply a methodology, based on density
      functional theory and the gauge-including projector augmented wave approach, to
      explore the effects of packing interactions on solid-state nuclear magnetic
      resonance (NMR) parameters. A visual map derived from a so-termed "magnetic
      shielding contribution field" can be made of the contributions to the magnetic
      shielding of a specific site-partitioning the chemical shift to specific
      interactions. The relation to the established approaches of examining the
      molecule to crystal change in the chemical shift and the nuclear independent
      chemical shift is established. The results are applied to a large sample of 71
      molecular crystals and three further specific examples from supermolecular
      chemistry and pharmaceuticals. This approach extends the NMR crystallography
      toolkit and provides insight into the development of both cluster based
      approaches to the predictions of chemical shifts and for empirical predictions of
      chemical shifts in solids.

PMID- 29031270
TI  - Robust determination of the chemical potential in the pole expansion and selected
      inversion method for solving Kohn-Sham density functional theory.
AB  - Fermi operator expansion (FOE) methods are powerful alternatives to
      diagonalization type methods for solving Kohn-Sham density functional theory
      (KSDFT). One example is the pole expansion and selected inversion (PEXSI) method,
      which approximates the Fermi operator by rational matrix functions and reduces
      the computational complexity to at most quadratic scaling for solving KSDFT.
      Unlike diagonalization type methods, the chemical potential often cannot be
      directly read off from the result of a single step of evaluation of the Fermi
      operator. Hence multiple evaluations are needed to be sequentially performed to
      compute the chemical potential to ensure the correct number of electrons within a
      given tolerance. This hinders the performance of FOE methods in practice. In this
      paper, we develop an efficient and robust strategy to determine the chemical
      potential in the context of the PEXSI method. The main idea of the new method is
      not to find the exact chemical potential at each self-consistent-field (SCF)
      iteration but to dynamically and rigorously update the upper and lower bounds for
      the true chemical potential, so that the chemical potential reaches its
      convergence along the SCF iteration. Instead of evaluating the Fermi operator for
      multiple times sequentially, our method uses a two-level strategy that evaluates
      the Fermi operators in parallel. In the regime of full parallelization, the wall
      clock time of each SCF iteration is always close to the time for one single
      evaluation of the Fermi operator, even when the initial guess is far away from
      the converged solution. We demonstrate the effectiveness of the new method using
      examples with metallic and insulating characters, as well as results from ab
      initio molecular dynamics.

PMID- 29031271
TI  - Two-dimensional mixture of amphiphilic dimers and spheres: Self-assembly
      behaviour.
AB  - The emergence of supramolecular aggregates from simple microscopic interaction
      rules is a fascinating feature of complex fluids which, besides its fundamental
      interest, has potential applications in many areas, from biological self-assembly
      to smart material design. We here investigate by Monte Carlo simulation the
      equilibrium structure of a two-dimensional mixture of asymmetric dimers and
      spheres (disks). Dimers and disks are hard particles, with an additional short
      range attraction between a disk and the smaller monomer of a dimer. The model
      parameters and thermodynamic conditions probed are typical of colloidal fluid
      mixtures. In spite of the minimalistic character of the interaction, we observe
      upon varying the relative concentration and size of the two colloidal species-a
      rich inventory of mesoscale structures at low temperature, such as clusters,
      lamellae (i.e., polymer-like chains), and gel-like networks. For colloidal
      species of similar size and near equimolar concentrations, a dilute fluid of
      clusters gives way to floating lamellae upon cooling; at higher densities, the
      lamellae percolate through the simulation box, giving rise to an extended
      network. A crystal-vapour phase-separation may occur for a mixture of dimers and
      much larger disks. Finally, when the fluid is brought in contact with a planar
      wall, further structures are obtained at the interface, from layers to branched
      patterns, depending on the nature of wall-particle interactions.

PMID- 29031272
TI  - Defect interaction and local structural distortions in Mg-doped LaGaO3: A
      combined experimental and theoretical study.
AB  - A combined experimental and theoretical study of Mg-doped LaGaO3 electrolyte was
      carried out, with the aim to unveil the interaction between oxygen vacancy (Vo)
      and perovskite B site cations. LaGaO3 (LG) and LaGa0.875Mg0.125O2.938 (LGM0125)
      samples were comprehensively characterized by X-ray absorption spectroscopy (XAS)
      and X-ray diffraction, in order to investigate short- and long-range structures
      of both undoped and Mg-doped materials. XAS analysis evidenced a preferential Ga
      Vo interaction in LGM0125, confirmed by periodic hybrid density functional theory
      calculations, which were combined with a symmetry-independent classes (SICs)
      approach in order to (a) obtain a detailed picture of the different Mg and Vo
      configurations in the doped material and (b) characterize the structural features
      of the conducting sites. Among the 28 structures of LGM0125 considered in the SIC
      approach, the Ga-Vo-Ga and Ga-Vo-Mg axial configurations (oriented along the b
      crystallographic axis) were found to be the most stable. The relative stability
      of all vacancy configurations considered could be related to geometric
      distortions of the B-sites, possibly significantly affecting the oxygen-ion
      diffusion process in such electrolytes.

PMID- 29031273
TI  - Post-transition state dynamics and product energy partitioning following thermal
      excitation of the F?HCH2CN transition state: Disagreement with experiment.
AB  - Born-Oppenheimer direct dynamics simulations were performed to study atomistic
      details of the F + CH3CN -> HF + CH2CN H-atom abstraction reaction. The
      simulation trajectories were calculated with a combined M06-2X/MP2 algorithm
      utilizing the 6-311++G** basis set. The experiments were performed at 300 K, and
      assuming the accuracy of transition state theory (TST), the trajectories were
      initiated at the F?HCH2CN abstraction TS with a 300 K Boltzmann distribution of
      energy and directed towards products. Recrossing of the TS was negligible,
      confirming the accuracy of TST. HF formation was rapid, occurring within 0.014 ps
      of the trajectory initiation. The intrinsic reaction coordinate (IRC) for
      reaction involves rotation of HF about CH2CN and then trapping in the CH2CN?HF
      post-reaction potential energy well of ~10 kcal/mol with respect to the HF +
      CH2CN products. In contrast to this IRC, five different trajectory types were
      observed: the majority proceeded by direct H-atom transfer and only 11%
      approximately following the IRC. The HF vibrational and rotational quantum
      numbers, n and J, were calculated when HF was initially formed and they increase
      as potential energy is released in forming the HF + CH2CN products. The
      population of the HF product vibrational states is only in qualitative agreement
      with experiment, with the simulations showing depressed and enhanced populations
      of the n = 1 and 2 states as compared to experiment. Simulations with an
      anharmonic zero-point energy constraint gave product distributions for relative
      translation, HF rotation, HF vibration, CH2CN rotation, and CH2CN vibration as
      5%, 11%, 60%, 7%, and 16%, respectively. In contrast, the experimental energy
      partitioning percentages to HF rotation and vibration are 6% and 41%. Comparisons
      are made between the current simulation and those for other F + H-atom
      abstraction reactions. The simulation product energy partitioning and HF
      vibrational population for F + CH3CN -> HF + CH2CN resemble those for other
      reactions. A detailed discussion is given of possible origins of the difference
      between the simulation and experimental energy partitioning dynamics for F +
      CH3CN -> HF + CH2CN. The F + CH3CN reaction also forms the CH3C(F)N intermediate,
      in which the F-atom adds to the C=N bond. However, this intermediate and F?CH3CN
      and CH3CN?F van der Waals complexes are not expected to affect the F + CH3CN ->
      HF + CH2CN product energy partitioning.

PMID- 29031274
TI  - A transition-state based rotational sudden (TSRS) approximation for polyatomic
      reactive scattering.
AB  - A transition-state based rotational sudden (TSRS) approximation for the
      calculation of differential and integral cross sections is introduced. The TSRS
      approach only requires data obtained from reactive scattering calculations for
      the vanishing total angular momentum (J = 0). It is derived within the quantum
      transition state framework and can be viewed as a generalization and improvement
      of existing J-shifting schemes. The TSRS approach assumes a sudden decay of the
      activated complex and separability of the overall rotation and motion in the
      internal coordinates. Depending on the choice of the body fixed frame, different
      variants of the TSRS can be derived. The TSRS approach is applied to the
      calculation of integral cross sections of various isotopomers of the H2O+H->H2+OH
      reaction, the reverse reaction H2+OH->H2O+H, and the H2O+Cl->HCl+OH reaction.
      Comparison with accurate close-coupling calculations and established approximate
      schemes shows that a scattering frame based TSRS approximation yields more
      accurate results than the centrifugal sudden approximation and standard J
      shifting for the H2O+H->H2+OH reaction and all isotopomers studied. For the H2+OH
      >H2O+H and the H2O+Cl->HCl+OH reactions, the TSRS results as well as the results
      of the other approximate schemes agree well with the exact ones. The findings are
      rationalized by an analysis of the different contributions to the moment of
      inertia matrix at the transition state geometry.

PMID- 29031275
TI  - Effective Floquet Hamiltonian theory of multiple-quantum NMR in anisotropic
      solids involving quadrupolar spins: Challenges and Perspectives.
AB  - The response of a quadrupolar nucleus (nuclear spin with I >12) to an oscillating
      radio-frequency pulse/field is delicately dependent on the ratio of the
      quadrupolar coupling constant to the amplitude of the pulse in addition to its
      duration and oscillating frequency. Consequently, analytic description of the
      excitation process in the density operator formalism has remained less
      transparent within existing theoretical frameworks. As an alternative, the
      utility of the "concept of effective Floquet Hamiltonians" is explored in the
      present study to explicate the nuances of the excitation process in multilevel
      systems. Employing spin I =32 as a case study, a unified theoretical framework
      for describing the excitation of multiple-quantum transitions in static isotropic
      and anisotropic solids is proposed within the framework of perturbation theory.
      The challenges resulting from the anisotropic nature of the quadrupolar
      interactions are addressed within the effective Hamiltonian framework. The
      possible role of the various interaction frames on the convergence of the
      perturbation corrections is discussed along with a proposal for a "hybrid method"
      for describing the excitation process in anisotropic solids. Employing suitable
      model systems, the validity of the proposed hybrid method is substantiated
      through a rigorous comparison between simulations emerging from exact numerical
      and analytic methods.

PMID- 29031276
TI  - Isotopic effects in vibrational relaxation dynamics of H on a Si(100) surface.
AB  - In a recent paper [U. Lorenz and P. Saalfrank, Chem. Phys. 482, 69 (2017)], we
      proposed a robust scheme to set up a system-bath model Hamiltonian, describing
      the coupling of adsorbate vibrations (system) to surface phonons (bath), from
      first principles. The method is based on an embedded cluster approach, using
      orthogonal coordinates for system and bath modes, and an anharmonic phononic
      expansion of the system-bath interaction up to second order. In this
      contribution, we use this model Hamiltonian to calculate vibrational relaxation
      rates of H-Si and D-Si bending modes, coupled to a fully H(D)-covered Si(100)
      (2*1) surface, at zero temperature. The D-Si bending mode has an anharmonic
      frequency lying inside the bath frequency spectrum, whereas the H-Si bending mode
      frequency is outside the bath Debye band. Therefore, in the present calculations,
      we only take into account one-phonon system-bath couplings for the D-Si system
      and both one- and two-phonon interaction terms in the case of H-Si. The
      computation of vibrational lifetimes is performed with two different approaches,
      namely, Fermi's golden rule, and a generalized Bixon-Jortner model built in a
      restricted vibrational space of the adsorbate-surface zeroth-order Hamiltonian.
      For D-Si, the Bixon-Jortner Hamiltonian can be solved by exact diagonalization,
      serving as a benchmark, whereas for H-Si, an iterative scheme based on the
      recursive residue generation method is applied, with excellent convergence
      properties. We found that the lifetimes obtained with perturbation theory, albeit
      having almost the same order of magnitude-a few hundred fs for D-Si and a couple
      of ps for H-Si-, are strongly dependent on the discretized numerical
      representation of the bath spectral density. On the other hand, the Bixon-Jortner
      model is free of such numerical deficiencies, therefore providing better
      estimates of vibrational relaxation rates, at a very low computational cost. The
      results obtained with this model clearly show a net exponential decay of the time
      dependent survival probability for the H-Si initial vibrational state, allowing
      an easy extraction of the bending mode "lifetime." This is in contrast with the D
      Si system, whose survival probability exhibits a non-monotonic decay, making it
      difficult to define such a lifetime. This different behavior of the vibrational
      decay is rationalized in terms of the power spectrum of the adsorbate-surface
      system. In the case of D-Si, it consists of several, non-uniformly distributed
      peaks around the bending mode frequency, whereas the H-Si spectrum exhibits a
      single Lorentzian lineshape, whose width corresponds to the calculated lifetime.
      The present work gives some insight into mechanisms of vibration-phonon coupling
      at surfaces. It also serves as a benchmark for multidimensional system-bath
      quantum dynamics, for comparison with approximate schemes such as reduced, open
      system density matrix theory (where the bath is traced out and a Liouville-von
      Neumann equation is solved) or approximate wavefunction methods to solve the
      combined system-bath Schrodinger equation.

PMID- 29031277
TI  - Resonant-convergent second-order nonlinear response functions at the levels of
      Hartree-Fock and Kohn-Sham density functional theory.
AB  - The second-order nonlinear (or cubic) response function is derived from the
      Ehrenfest theorem with inclusion made of the finite lifetimes of the excited
      states, representing the extension of the derivation of the quadratic response
      function in the same framework [P. Norman et al., J. Chem. Phys. 123, 194103
      (2005)]. The resulting damped response functions are physically sound and
      converging also in near-resonance and resonance regions of the spectrum. Being an
      accurate approximation for small complex frequencies (defined as the sum of an
      optical frequency and an imaginary damping parameter), the polynomial expansion
      of the complex cubic response function in terms of the said frequencies is
      presented and used to validate the program implementation. In terms of
      approximate state theory, the computationally tractable expressions of the damped
      cubic response function are derived and implemented at the levels of Hartree-Fock
      and Kohn-Sham density functional theory. Numerical examples are provided in terms
      of studies of the intensity-dependent refractive index of para-nitroaniline and
      the two-photon absorption cross section of neon. For the latter property, a
      numerical comparison is made against calculations of the square of two-photon
      matrix elements that are identified from a residue analysis of the resonance
      divergent quadratic response function.

PMID- 29031278
TI  - Activity coefficients from molecular simulations using the OPAS method.
AB  - A method for determining activity coefficients by molecular dynamics simulations
      is presented. It is an extension of the OPAS (osmotic pressure for the activity
      of the solvent) method in previous work for studying the solvent activity in
      electrolyte solutions. That method is extended here to study activities of all
      components in mixtures of molecular species. As an example, activity coefficients
      in liquid mixtures of water and methanol are calculated for 298.15 K and 323.15 K
      at 1 bar using molecular models from the literature. These dense and strongly
      interacting mixtures pose a significant challenge to existing methods for
      determining activity coefficients by molecular simulation. It is shown that the
      new method yields accurate results for the activity coefficients which are in
      agreement with results obtained with a thermodynamic integration technique. As
      the partial molar volumes are needed in the proposed method, the molar excess
      volume of the system water + methanol is also investigated.

PMID- 29031279
TI  - Rotationally inelastic collisions of excited NaK and NaCs molecules with noble
      gas and alkali atom perturbers.
AB  - We report measurements of rate coefficients at T ~ 600 K for rotationally
      inelastic collisions of NaK molecules in the 2(A)1Sigma+ electronic state with
      helium, argon, and potassium atom perturbers. Several initial rotational levels J
      between 14 and 44 were investigated. Collisions involving molecules in low-lying
      vibrational levels (v = 0, 1, and 2) of the 2(A)1Sigma+ state were studied using
      Fourier-transform spectroscopy. Collisions involving molecules in a higher
      vibrational level, v = 16, were studied using pump/probe, optical-optical double
      resonance spectroscopy. In addition, polarization spectroscopy measurements were
      carried out to study the transfer of orientation in these collisions. Many, but
      not all, of the measurements were carried out in the "single-collision regime"
      where more than one collision is unlikely to occur within the lifetime of the
      excited molecule. The analysis of the experimental data, which is described in
      detail, includes an estimate of effects of multiple collisions on the reported
      rate coefficients. The most significant result of these experiments is the
      observation of a strong propensity for DeltaJ = even transitions in collisions
      involving either helium or argon atoms; the propensity is much stronger for
      helium than for argon. For the initial rotational levels studied experimentally,
      almost all initial orientation is preserved in collisions of NaK 2(A)1Sigma+
      molecules with helium. Roughly between 1/3 and 2/3 of the orientation is
      preserved in collisions with argon, and almost all orientation is destroyed in
      collisions with potassium atoms. Complementary measurements on rotationally
      inelastic collisions of NaCs 2(A)1Sigma+ with argon do not show a DeltaJ = even
      propensity. The experimental results are compared with new theoretical
      calculations of collisions of NaK 2(A)1Sigma+ with helium and argon. The
      calculations are in good agreement with the absolute magnitudes of the
      experimentally determined rate coefficients and accurately reproduce the very
      strong propensity for DeltaJ = even transitions in helium collisions and the less
      strong propensity for DeltaJ = even transitions in argon collisions. The
      calculations also show that collisions with helium are less likely to destroy
      orientation than collisions with argon, in agreement with the experimental
      results.

PMID- 29031280
TI  - Factors influencing suicide in older rural males: a review of Australian studies.
AB  - INTRODUCTION: Suicide remains an important public health issue in Australia,
      responsible for around 2500 deaths each year. Although suicide only accounts for
      around 1.7% of total mortality in Australia per year, 75% of suicide deaths are
      in males. This article reviews the factors contributing to suicide in older rural
      males in Australia and then categorises the papers into themes for ease of
      explanation. Living with experiences of drought, dramatic weather change, lower
      employment opportunities, out-migration, changing family dynamics, ageism in the
      community, economic change and competitive labour markets, all add to the diverse
      experience for an older person who is ageing in a rural setting. METHODS: A
      literature search was conducted in March 2015, using the terms 'elderly' and
      'older males' and then combined with 'rural', 'suicide' and 'Australia', to
      investigate the amount of research that has been conducted on the factors
      relating to suicide in older rural Australian males. RESULTS: Reviewed articles
      consisted of research using either quantitative or qualitative approaches, which
      investigated suicide in older Australians published between 1950 and 2014. With
      strict adherence to the selection criteria, articles (21 in total) were removed
      because they were a literature review; a narrative review; they focused
      predominantly on youth or suicide risk, suicidal ideation or suicide attempts; or
      they discussed reasons for living. This article discusses the researcher's
      recommendations for further research into employment transitions for older
      Australian males, and the need to review policy change for further intervention
      in the future. CONCLUSIONS: This article highlights factors that may cause older
      rural Australians to be placed at a higher risk of suicide than their urban
      dwelling counterparts. With the impact of the changing economy, unpredictable
      climatic conditions and dynamic changes in rural Australian families, there is a
      need to highlight research that has been conducted in this area. Future research
      should focus on identification of misclassification of suicide deaths,
      investigation of the possible effect that retirement pathways may have on older
      Australian males, suicide prevention strategies, mental wellbeing and the risk of
      suicidal behaviour. This will ascertain any compounding or protective factors
      that could influence this current trend.

PMID- 29031281
TI  - Double disparities in the health care for people with schizophrenia of an ethnic
      national minority.
AB  - BACKGROUND: Studies have shown health care disparities among persons of minority
      status, including in countries with universal health care. Yet, a dearth of
      studies have addressed disparities resulting from the combined effect of two
      minority status groups: severe mental illness and ethnic-national sector
      filiation. This study aimed to compare the differential health care of Jewish-
      and Arab-Israelis with schizophrenia in a country with a universal health
      insurance. METHOD: This study builds on a large case-control epidemiological
      sample (N = 50,499) of Jewish- (92.9%) and Arab-Israelis (7.1%) service users
      with (n = 16,833) and without schizophrenia (n = 33,666). Health services records
      were collected in the years 2000-2009. Diabetes and cardiovascular disease (CVD)
      served as sentinel diseases. We compared annual number of LDL tests and visits to
      specialists in the entire sample, Hemoglobin-A1C test among people diagnosed with
      diabetes, and cardiac surgical interventions for those diagnosed with CVD.
      RESULTS: Service users with schizophrenia were less likely to meet identical
      indexes of care as their study counterparts: 95% of cholesterol tests (p < .001),
      and 92% visits to specialists (p < .001). These differences were greater among
      Arab- compared to Jewish-Israelis. Annual frequency of Hemoglobin-A1C test among
      people diagnosed with diabetes was lower (94%) in people with schizophrenia (p <
      0.01), but no ethnic-national differences were identified. Among service users
      with CVD less surgical interventions were done in people with schizophrenia (70%)
      compared to their counterparts, with no ethnic-national disparities. CONCLUSIONS:
      In Israel, service users with schizophrenia fail to receive equitable levels of
      medical and cardiac surgical care for CVD and regular laboratory tests for
      diabetes. Although disparities in some health indicators were enhanced among Arab
      Israelis, schizophrenia was a greater source of disparities than ethnic-national
      filiation.

PMID- 29031282
TI  - Dengue Virus Serotypes 1 and 2 Responsible for Major Dengue Outbreaks in Nepal:
      Clinical, Laboratory, and Epidemiological Features.
AB  - Dengue virus (DENV) is expanding toward previously nonendemic areas. DENV has
      recently been introduced in Nepal with limited information. We report the
      clinical features and serotype distribution of DENV in Nepal during the 2010
      outbreaks. A total of 1,215 clinical dengue cases at two major hospitals of
      central and western Nepal were investigated. Demographic, clinical, and
      laboratory parameters were recorded. Serum specimens were tested for DENV by
      IgM/IgG enzyme-linked immunosorbent assays (ELISAs) and reverse transcription
      polymerase chain reaction (RT-PCR). We confirmed DENV infection in 403 (33%)
      patients from 12 districts with an estimated case fatality rate of 1.5%. DENV
      infection was more common in adults (87%) and urban settings (74%). We detected
      all four serotypes but DENV-1 and -2 were mainly responsible for major outbreaks
      (92%). Overall, 60% of all DENV infections were secondary and 17% were severe
      dengue; both being more frequent among the DENV-2 infections. Rash, bleeding,
      abdominal pain, hepatomegaly, elevated liver enzymes, and thrombocytopenia were
      significantly more common in severe dengue compared with nonsevere infections. We
      also confirmed the expansion of dengue to hill urban areas (DENV-1 and -2),
      including the capital Kathmandu (altitude, 1,300 m) though > 90% cases were from
      southern plains. Differential clinical and laboratory features probably help in
      clinical decisions. Multiple serotypes circulation and elevated secondary
      infections pose potential risk of severe outbreaks and deaths in the future.
      Therefore, a country with recent dengue introduction, like Nepal, urgently
      requires a systematic surveillance and appropriate control measures in place to
      respond to any disastrous outbreaks.

PMID- 29031284
TI  - Papulonecrotic Tuberculid.

PMID- 29031283
TI  - Multipathway Quantitative Assessment of Exposure to Fecal Contamination for Young
      Children in Low-Income Urban Environments in Accra, Ghana: The SaniPath
      Analytical Approach.
AB  - Lack of adequate sanitation results in fecal contamination of the environment and
      poses a risk of disease transmission via multiple exposure pathways. To better
      understand how eight different sources contribute to overall exposure to fecal
      contamination, we quantified exposure through multiple pathways for children
      under 5 years old in four high-density, low-income, urban neighborhoods in Accra,
      Ghana. We collected more than 500 hours of structured observation of behaviors of
      156 children, 800 household surveys, and 1,855 environmental samples. Data were
      analyzed using Bayesian models, estimating the environmental and behavioral
      factors associated with exposure to fecal contamination. These estimates were
      applied in exposure models simulating sequences of behaviors and transfers of
      fecal indicators. This approach allows us to identify the contribution of any
      sources of fecal contamination in the environment to child exposure and use
      dynamic fecal microbe transfer networks to track fecal indicators from the
      environment to oral ingestion. The contributions of different sources to exposure
      were categorized into four types (high/low by dose and frequency), as a basis for
      ranking pathways by the potential to reduce exposure. Although we observed
      variation in estimated exposure (108-1016 CFU/day for Escherichia coli) between
      different age groups and neighborhoods, the greatest contribution was
      consistently from food (contributing > 99.9% to total exposure). Hands played a
      pivotal role in fecal microbe transfer, linking environmental sources to oral
      ingestion. The fecal microbe transfer network constructed here provides a
      systematic approach to study the complex interaction between contaminated
      environment and human behavior on exposure to fecal contamination.

PMID- 29031285
TI  - Evaluation of Community-Directed Operation of Black Fly Traps for Entomological
      Surveillance of Onchocerca volvulus Transmission in the Madi-Mid North Focus of
      Onchocerciasis in Northern Uganda.
AB  - Entomological measures of transmission are important metrics specified by the
      World Health Organization to document the suppression and interruption of
      transmission of Onchocerca volvulus, the causative agent of onchocerciasis. These
      metrics require testing of large numbers of vector black flies. Black fly
      collection has relied on human landing collections, which are inefficient and
      potentially hazardous. As the focus of the international community has shifted
      from onchocerciasis control to elimination, replacement of human landing
      collections has become a priority. The Esperanza window trap (EWT) has shown
      promise as an alternative method for collection of Simulium damnosum s.l., the
      primary vector of O. volvulus in Africa. Here, we report the results of a
      community-based trial of the EWT in northern Uganda. Traps operated by residents
      were compared with human landing collections in two communities over 5 months.
      Three traps, when operated by a single village resident, collected over four
      times as many S. damnosum as did the two-men collection team. No significant
      differences were noted among the bait formulations. The results suggest that EWTs
      may be effectively operated by community residents and that the trap represents a
      viable alternative to human landing collections for entomological surveillance of
      O. volvulus transmission.

PMID- 29031286
TI  - Surveillance of Vector-Borne Infections (Chikungunya, Dengue, and Malaria) in Bo,
      Sierra Leone, 2012-2013.
AB  - Malaria remains a significant cause of morbidity and mortality in West Africa,
      but the contribution of other vector-borne infections (VBIs) to the burden of
      disease has been understudied. We used rapid diagnostic tests (RDTs) for three
      VBIs to test blood samples from 1,795 febrile residents of Bo City, Sierra Leone,
      over a 1-year period in 2012-2013. In total, 24% of the tests were positive for
      malaria, fewer than 5% were positive for markers of dengue virus infection, and
      39% were positive for IgM directed against chikungunya virus (CHIKV) or a related
      alphavirus. In total, more than half (55%) of these febrile individuals tested
      positive for at least one of the three VBIs, which highlights the very high
      burden of vector-borne diseases in this population. The prevalence of positives
      on the Chikungunya IgM and dengue tests did not vary significantly with age (P >
      0.36), but higher rates of malaria were observed in children < 15 years of age (P
      < 0.001). Positive results on the Chikungunya IgM RDTs were moderately correlated
      with rainfall (r2 = 0.599). Based on the high prevalence of positive results on
      the Chikungunya IgM RDTs from individuals Bo and its environs, there is a need to
      examine whether an ecological shift toward a greater burden from CHIKV or related
      alphaviruses is occurring in other parts of Sierra Leone or the West African
      region.

PMID- 29031287
TI  - Leprosy Associated with Atypical Cutaneous Leishmaniasis in Nicaragua and
      Honduras.
AB  - In Central America, few cases of leprosy have been reported, but the disease may
      be unrecognized. Diagnosis is based on clinical criteria and histology.
      Preliminary field work in Nicaragua and Honduras found patients, including many
      children, with skin lesions clinically suggestive of atypical cutaneous
      leishmaniasis or indeterminate leprosy. Histology could not distinguish these
      diseases although acid-fast organisms were visible in a few biopsies. Lesions
      healed after standard antimicrobial therapy for leprosy. In the present study,
      patients, family members, and other community members were skin-tested and
      provided nasal swabs and blood samples. Biopsies were taken from a subgroup of
      patients with clinical signs of infection. Two laboratories analyzed samples,
      using local in-house techniques. Mycobacterium leprae, Leishmania spp. and
      Leishmania infantum were detected using polymerase chain reactions. Mycobacterium
      leprae DNA was detected in blood samples and nasal swabs, including some cases
      where leprosy was not clinically suspected. Leishmania spp. were also detected in
      blood and nasal swabs. Most biopsies contained Leishmania DNA and coinfection of
      Leishmania spp. with M. leprae occurred in 33% of cases. Mycobacterium leprae DNA
      was also detected and sequenced from Nicaraguan and Honduran environmental
      samples. In conclusion, leprosy and leishmaniasis are present in both regions,
      and leprosy appears to be widespread. The nature of any relationship between
      these two pathogens and the epidemiology of these infections need to be
      elucidated.

PMID- 29031288
TI  - Case Report: Old World Mucosal Leishmaniasis: Report of Five Imported Cases to
      the Hospital for Tropical Diseases, London, United Kingdom.
AB  - Old World species of Leishmania typically cause visceral and cutaneous
      leishmaniasis. Mucosal involvement is typically seen with infection by Leishmania
      species found in South America, usually after the healing of cutaneous
      leishmaniasis. We present five imported cases of mucosal leishmaniasis caused by
      Old World Mediterranean Leishmania infantum exclusively affecting the nasal
      mucosa or vocal cord. In only one case was there a recollection of a preceding
      cutaneous lesion compatible with cutaneous Leishmaniasis. Of significance was
      that four out of five cases were receiving local corticosteroids for chronic lung
      disorders and four were systemically immunosuppressed. This report highlights the
      importance of considering mucosal leishmaniasis in the differential diagnosis in
      those presenting with upper respiratory tract mucosal lesions with a relevant
      travel history to the Mediterranean and in whom malignancy has been excluded.

PMID- 29031289
TI  - Histological Examination in Obtaining a Diagnosis in Patients with
      Lymphadenopathy in Lima, Peru.
AB  - The differential diagnosis for lymphadenopathy is wide and clinical presentations
      overlap, making obtaining an accurate diagnosis challenging. We sought to
      characterize the clinical and radiological characteristics, histological
      findings, and diagnoses for a cohort of patients with lymphadenopathy of unknown
      etiology. 121 Peruvian adults with lymphadenopathy underwent lymph node biopsy
      for microbiological and histopathological evaluation. Mean patient age was 41
      years (Interquartile Range 26-52), 56% were males, and 39% were HIV positive.
      Patients reported fever (31%), weight loss (23%), and headache (22%); HIV
      infection was associated with fever (P < 0.05) and gastrointestinal symptoms (P <
      0.05). Abnormalities were reported in 40% of chest X-rays (N = 101). Physicians
      suspected TB in 92 patients (76%), lymphoma in 19 patients (16%), and other
      malignancy in seven patients (5.8%). Histological diagnoses (N = 117) included
      tuberculosis (34%), hyperplasia (27%), lymphoma (13%), and nonlymphoma malignancy
      (14%). Hyperplasia was more common (P < 0.001) and lymphoma less common (P =
      0.005) among HIV-positive than HIV-negative patients. There was a trend toward
      reduced frequency of caseous necrosis in samples from HIV-positive than HIV
      negative TB patients (67 versus 93%, P = 0.055). The spectrum of diagnoses was
      broad, and clinical and radiological features correlated poorly with diagnosis.
      On the basis of clinical features, physicians over-diagnosed TB, and under
      diagnosed malignancy. Although this may not be inappropriate in resource-limited
      settings where TB is the most frequent easily treatable cause of lymphadenopathy,
      diagnostic delays can be detrimental to patients with malignancy. It is important
      that patients with lymphadenopathy undergo a full diagnostic work-up including
      sampling for histological evaluation to obtain an accurate diagnosis.

PMID- 29031290
TI  - Privately practising nurse practitioners' provision of care subsidised through
      the Medicare Benefits Schedule and the Pharmaceutical Benefits Scheme in
      Australia: results from a national survey.
AB  - Objective Since legislative changes in 2010, certain health care services
      provided by privately practising nurse practitioners (PPNPs) in Australia have
      been eligible for reimbursement under the Medicare Benefits Schedule (MBS) and
      the Pharmaceutical Benefits Scheme (PBS). The aim of the present study was to
      describe survey results relating to the care provided by PPNPs subsidised through
      the MBS and PBS.Methods PPNPs in Australia were invited to complete an electronic
      survey exploring their practice activities. Quantitative data were analysed using
      descriptive statistics and 95% confidence intervals were calculated for
      percentages where relevant. Free text data were analysed using thematic
      analysis.Results Seventy-three PPNPs completed the survey. The most common form
      of payment reported (34%; n=25) was payment by direct fee for service (MBS rebate
      only, also known as bulk billing). Seventy-five per cent of participants (n=55)
      identified that there were aspects of care delivery not adequately described and
      compensated by the current nurse practitioner (NP) MBS item numbers. 87.7% (n=64)
      reported having a PBS prescriber authorisation number. Themes identified within
      the free text data that related to the constraints of the MBS and PBS included
      'duplication of services' and 'level of reimbursement'.Conclusion The findings of
      the present study suggest that PPNPs are providing subsidised care through the
      MBS and PBS. The PPNPs in the present study reported challenges with the current
      structure and breadth of the NP MBS and PBS items, which restrict them from
      providing complete episodes of patient care.What is known about the topic? Since
      the introduction of legislative changes in 2010, services provided by PPNPs in
      Australia have been eligible for subsidisation through the MBS and PBS.What does
      this paper add? This paper provides data on PPNPs' provision of care subsidised
      through the MBS and PBS.What are the implications for practitioners? Eligibility
      to provide care subsidised through the MBS and PBS has enabled the establishment
      of PPNP services. The current breadth and structure of the NP MBS and PBS item
      numbers have restricted the capacity of PPNPs to provide complete episodes of
      patient care.

PMID- 29031291
TI  - Metal speciation analysis of petroleum: Myth or reality?
AB  - Metals occurring in crude oil in a great variety of complexed forms are minor but
      important constituents as they affect the refining and production operations, as
      well as participate in geochemical processes. These roles of metals are thought
      to be related to their chemical state the knowledge of which requires performing
      speciation analysis. While exact metal speciation in crude oil still remains
      obscure, earnest efforts to decipher it based on using up-to-date hyphenated
      techniques have been attempted in the past decade. With various levels of
      fractionation of vanadium and nickel species, liquid chromatography with ICP-MS
      detection allows for an insight into metal distribution in crude oil or its
      fractions, according to species molecular weight or polarity. Further speciation
      information on the metal coordination in a variety of porphyrin compounds can be
      gained by the use of Fourier transform ion cyclotron resonance mass spectrometry.
      Individual species of mercury are often available for quantification with gas
      chromatography-ICP-MS as the method of choice. This mini-review is aimed at
      revealing and giving rise to the development of those speciation strategies and
      approaches that can achieve the objectives of identification, characterization
      and determination of metal species in crude oil and its fractions.

PMID- 29031292
TI  - A new integrated TLC/MU-ATR/SERS advanced approach for the identification of
      trace amounts of dyes in mixtures.
AB  - The present research is focused on the setting up of an advanced analytical
      system for the detection of synthetic dyes. The system is based on the
      combination of an innovative thin layer chromatography (TLC) plate coupled with
      enhanced infrared (MU-ATR, metal underlayer attenuated total reflection) and
      Surface Enhanced Raman (SERS) spectroscopy. In particular, a TLC plate made of
      silver iodide (AgI) applied onto a gold coated glass slide (AgI@Au) is proposed
      as an efficient stationary phase for the separation of dyes mixtures. The
      separated dyes are then identified by means of both enhanced FTIR and SERS,
      performed directly on the same eluted spots. The use of a mid-IR transparent
      inorganic salt as stationary phase coupled with the underneath gold layer avoids
      spectral interferences, enhancing the signal obtained from ATR analyses. At the
      same time, SERS spectra can be recorded as the TLC plate may act as a SERS active
      substrate due to the photoreduction of AgI to metallic Ag caused by the exposure
      to the laser during the Raman analysis. Different mixtures of synthetic dyes of
      known composition, widely used in dyeing processes, have been tested and the
      method resulted to be effective in identifying trace amounts in the order of tens
      nanograms. Moreover, the method has been further evaluated on a real case study
      represented by dyes extracted from dyed wool.

PMID- 29031293
TI  - In situ one-pot synthesis of graphitic carbon nitride quantum dots and its
      2,2,6,6-tetramethyl(piperidin-1-yl)oxyl derivatives as fluorescent nanosensors
      for ascorbic acid.
AB  - Graphitic carbon nitride quantum dots (gCNQDs) when alone or containing embedded
      4-amino-2,2,6,6-tetramethyl(piperidin-1-yl)oxyl) (4-AT) (gCNQDs-4-AT(embedded))
      were synthesized via low temperature in situ one-pot process from
      diaminomaleonitrile (DAMN). The blue emission of both gCNQDs and gCNQDs-4-AT were
      excitation wavelength-dependent with very high fluorescence quantum yields of 43
      and 51%, respectively. Further, the gCNQDs were covalently linked to 4-AT via an
      amide bond to give (gCNQDs-4-AT (linked)). gCNQDs were also non-covalently linked
      to 2,2,6,6-etramethyl(piperidin-1-yl)oxyl (TEMPO, not containing amino groups)
      derivatized zinc phthalocyanine (ZnPc) to form gCNQDs-TEMPO-ZnPc(pi-pi). The
      TEMPO-derivatized gCNQDs (gCNQDs-4-AT(embedded)), gCNQDs-4-AT(linked), or gCNQDs
      TEMPO-ZnPc(pi-pi) were found to be highly sensitive and selective fluorescent
      probes for ascorbic acid (AA) detection with limits of detection (LOD) in the
      nanomolar range. Hence, 4-AT (or TEMPO) functionality introduced into the gCNQDs
      (or ZnPc) afforded the derivation of selective and sensitive AA probes. Real
      samples were evaluated by the designed probes and satisfactory recoveries further
      confirmed the analytical applicability of the gCNQDs-based probes.

PMID- 29031294
TI  - A label-free and highly sensitive strategy for uracil-DNA glycosylase activity
      detection based on stem-loop primer-mediated exponential amplification (SPEA).
AB  - Uracil-DNA glycosylase (UDG) plays essential roles in base excision repair (BER)
      pathway by eliminating uracil from DNA to sustain the genome integrity. Sensitive
      detection of UDG activity is of great significance in the study of many
      fundamental biochemical processes and clinical applications. We develop a label
      free method for UDG activity detection using stem-loop primer-mediated
      exponential amplification (SPEA). In the presence of active UDG, the uracil base
      in helper hairpin probe (HP) can be excised to generate an abasic site (AP site),
      which can be cleaved by endonuclease IV (Endo IV) with a blocked primer released.
      This primer then triggers the strand displacement reaction to produce a dumb-bell
      structure DNA, which can initiate a loop-mediated isothermal amplification (LAMP)
      reaction. This reaction generates a large number of long double-strand DNA
      replicates, which can be stained by SYBR Green (SG) I to deliver enhanced
      fluorescence for quantitative detection of UDG activity. A linear range from
      0.001 U/mL to 1 U/mL and a detection limit down to 0.00068 U/mL are achieved.
      This strategy has also been demonstrated for UDG assay in complex cell lysates,
      implying its great potential for UDG based clinical diagnostics and therapeutics.

PMID- 29031295
TI  - Competitive amperometric immunosensor for determination of p53 protein in urine
      with carbon nanotubes/gold nanoparticles screen-printed electrodes: A potential
      rapid and noninvasive screening tool for early diagnosis of urinary tract
      carcinoma.
AB  - Since p53 protein has become recognized biomarker for both diagnostic and
      therapeutic purposes in oncological diseases with particular relevance for
      bladder cancer, it is highly desirable to search for a novel sensing tool for
      detecting the patient's p53 level at the early stage. Here we report the first
      study on the development and validation of a novel disposable competitive
      amperometric immunosensor for determination of p53 protein at subnanomolar
      levels, based on p53 immobilization on gold nanoparticles/carbon nanotubes
      modified screen-printed carbon electrodes. The assay protocol requires the use of
      single anti-p53 mouse monoclonal antibody (DO-7 clone), able to recognize both
      wild-type and mutant p53. The developed immunosensor as well as the protocol of
      the electrochemical immunoassay were optimized by means of an experimental design
      procedure to assess the suitability of the device to be validated and applied for
      the determination of p53 in untreated and undiluted urine samples. It was found
      that the developed competitive immunodevice was able to achieve wide linear range
      detection of wild-type p53 from 20 pM to 10 nM with a low detection limit of 14
      pM in synthetic urine samples, suggesting the sensor's capability of working in a
      complex sample matrix. The excellent performance results also in terms of
      selectivity, trueness and precision, coupled with the advantages of an easy
      preparation and low-cost assay in contrast to other methods which require very
      complex, time-consuming and costly nanostructured architectures, makes the
      developed competitive immunosensor an analytically robust diagnostic tool,
      valuable for implementation of screening and follow-up programs in patients with
      urologic malignancies.

PMID- 29031296
TI  - Corrigendum to "A simple and rapid method for isotopic analysis of nickel,
      copper, and zinc in seawater using chelating extraction and anion exchange"
      [Anal. Chim. Acta 967 (2017) 1-11].

PMID- 29031297
TI  - 3-Dimensional X-ray microtomography methodology for characterization of
      monolithic stationary phases and columns for capillary liquid chromatography - A
      tutorial.
AB  - In this tutorial we describe a fast, nondestructive, three-dimensional (3-D) view
      approach to be used in morphology characterization of capillary monoliths and
      columns by reconstruction from X-ray microtomography (XMT) obtained by acquiring
      projection images of the sample from a number of different directions. The method
      comprises imaging acquisition, imaging reconstruction using specific algorithms
      and imaging analysis by generation of a 3-D image of the sample from radiographic
      images. The 3-D images show the morphological data for bulk macropore space and
      skeleton connectivity of the monoliths and were compared with other images from
      imaging techniques such as scanning electron microscopy (SEM) and field emission
      scanning electron microscopy (FESEM) and with chromatographic performance. The 3
      D XMT methodology is applicable for organic and inorganic capillary
      chromatographic monolithic materials and it allows the acquisition of many
      hundreds (in our case 1001 projections) of longitudinal and cross-sectional
      images in a single session, resolving morphological details with a 3D-view of the
      monolithic structure, inclusive inside the column in a sectional structure with
      volume (three dimensions) when compared to the sectional structure area (with
      only two dimensions) when using SEM and FESEM techniques.

PMID- 29031298
TI  - Game meat authentication through rare earth elements fingerprinting.
AB  - Accurate labelling of meat (e.g. wild versus farmed, geographical and genetic
      origin, organic versus conventional, processing treatment) is important to inform
      the consumers about the products they buy. Meat and meat products declared as
      game have higher commercial value making them target to fraudulent labelling
      practices and replacement with non-game meat. We have developed and validated a
      new method for authentication of wild rabbit meat using elemental metabolomics
      approach. Elemental analysis was performed using rapid ultra-trace multi-element
      measurement by inductively coupled plasma mass spectrometry (ICP-MS). Elemental
      signatures showed excellent ability to discriminate the wild rabbit from non-wild
      rabbit meat. Our results demonstrate the usefulness of metabolic markers -rare
      earth signatures, as well as other trace element signatures for game meat
      authentication.

PMID- 29031299
TI  - Marker discovery in volatolomics based on systematic alignment of GC-MS signals:
      Application to food authentication.
AB  - Starting with an experiment to authenticate walnut oils based on GC-MS analysis
      of the volatolome, this paper aims to demonstrate the relevance of a two-step
      alignment-based strategy for the systematic research of VOC markers. The first
      step of the treatment consists of roughly reducing the time shifts with
      efficient, known warping techniques like COW (Correlation Optimized Warping). The
      second step relies on an accurate peak apex alignment in order to refine residual
      local misalignments and to enable further systematic marker research through
      univariate or multivariate data treatments. This two-step strategy was
      implemented on 117 GC-MS analyses of the volatolome of three vegetable oils with
      very similar composition. During the analysis campaign, the GC-MS system was
      intentionally subjected to instrumental drifts in order to generate realistic
      signal shifts. The first part of this study aims to assess the efficiency of the
      warping-based strategy in terms of signal alignment and sample discrimination.
      Whereas no distinction between the three oils was possible with unaligned raw GC
      MS data, the application of COW enabled a significant but insufficient
      improvement of both reduction of temporal drifts and between-group separation
      with 79% of samples being well-classified according to Linear Discriminant
      Analysis (LDA). Applying the peak apex alignment procedure to COW-treated signals
      resulted in a suitable correction of the remaining local distortions and improved
      the proportion of well-classified samples in LDA to 100%. The second part of this
      study assesses the robustness of the discriminant markers highlighted in this
      approach by: (i) discussing the relevance of the best markers involved in the LDA
      model, where a close review of literature confirmed the consistency for two of
      them, and (ii) validating highlighted makers by retrieving the set of the 23
      markers previously determined by manual processing among those automatically
      found. The third part shows the potential of the systematic approach for
      untargeted detection of 184 highly significant relevant markers from the oil
      volatolome. Finally, the fourth part presents a comparison of our hybrid
      alignment strategy with two reference alignment methods (iCoshift and STW) in
      order to assess quality alignment of the GC-MS data and to show the three
      methods' abilities to detect discriminant markers.

PMID- 29031300
TI  - Optimal preprocessing of serum and urine metabolomic data fusion for staging
      prostate cancer through design of experiment.
AB  - Accurate classification of cancer stages will achieve precision treatment for
      cancer. Metabolomics presents biological phenotypes at the metabolite level and
      holds a great potential for cancer classification. Since metabolomic data can be
      obtained from different samples or analytical techniques, data fusion has been
      applied to improve classification accuracy. Data preprocessing is an essential
      step during metabolomic data analysis. Therefore, we developed an innovative
      optimization method to select a proper data preprocessing strategy for
      metabolomic data fusion using a design of experiment approach for improving the
      classification of prostate cancer (PCa) stages. In this study, urine and serum
      samples were collected from participants at five phases of PCa and analyzed using
      a 1H NMR-based metabolomic approach. Partial least squares-discriminant analysis
      (PLS-DA) was used as a classification model and its performance was assessed by
      goodness of fit (R2) and predictive ability (Q2). Results show that data
      preprocessing significantly affect classification performance and depends on data
      properties. Using the fused metabolomic data from urine and serum, PLS-DA model
      with the optimal data preprocessing (R2 = 0.729, Q2 = 0.504, P < 0.0001) can
      effectively improve model performance and achieve a better classification result
      for PCa stages as compared with that without data preprocessing (R2 = 0.139, Q2 =
      0.006, P = 0.450). Therefore, we propose that metabolomic data fusion integrated
      with an optimal data preprocessing strategy can significantly improve the
      classification of cancer stages for precision treatment.

PMID- 29031301
TI  - Zwitterionic-hydrophilic interaction capillary liquid chromatography coupled to
      tandem mass spectrometry for the characterization of human alpha-acid
      glycoprotein N-glycan isomers.
AB  - In this work, a MUZIC-HILIC-MS/MS methodology was established in negative ion
      mode for the characterization of glycan isomers. The possibility to separate the
      glycan isomers by the MUZIC-HILIC strategy coupled to a high resolution tandem
      mass spectrometry detection permitted us to obtain valuable information about
      each glycan structure. The most important diagnostic ion fragments previously
      described to characterize structural features of glycans, were evaluated in this
      study using hAGP as model glycoprotein. The assignation of hAGP glycan isomers
      performed in our previous work using the GRIL strategy in combination with
      exoglycosidase digestion [1] was used in this paper to confirm or discard some
      ion fragments reported in the literature and delve into the structural
      characterization of glycan isomers. Sialic acid as well as fucose linkage-type
      glycan isomers were assigned using this approach and daughter ions with higher
      diagnostic value were determined. The location of alpha2-3/alpha2-6 sialic acids
      on antennas and a deeper characterization of several highly sialylated tri- and
      tetraantennary glycans was also possible using the established MS/MS method.
      Moreover, relying on the characterization performed in Ref. [1], core and antenna
      fucosylation were differentiated in this work using specific ion fragments
      obtained in the tandem mass spectra. This methodology was also applied to hAGP
      purified from control and pathological serum samples, which corroborated its
      robustness and its potential for finding novel glycan-based biomarkers in patho
      glycomic studies.

PMID- 29031302
TI  - Fast quantitation of opioid isomers in human plasma by differential mobility
      spectrometry/mass spectrometry via SPME/open-port probe sampling interface.
AB  - Mass spectrometry (MS) based quantitative approaches typically require a thorough
      sample clean-up and a decent chromatographic step in order to achieve needed
      figures of merit. However, in most cases, such processes are not optimal for
      urgent assessments and high-throughput determinations. The direct coupling of
      solid phase microextraction (SPME) to MS has shown great potential to shorten the
      total sample analysis time of complex matrices, as well as to diminish potential
      matrix effects and instrument contamination. In this study, we demonstrate the
      use of the open-port probe (OPP) as a direct and robust sampling interface to
      couple biocompatible-SPME (Bio-SPME) fibres to MS for the rapid quantitation of
      opioid isomers (i.e. codeine and hydrocodone) in human plasma. In place of
      chromatography, a differential mobility spectrometry (DMS) device was implemented
      to provide the essential selectivity required to quantify these constitutional
      isomers. Taking advantage of the simplified sample preparation process based on
      Bio-SPME and the fast separation with DMS-MS coupling via OPP, a high-throughput
      assay (10-15 s per sample) with limits of detection in the sub-ng/mL range was
      developed. Succinctly, we demonstrated that by tuning adequate ion mobility
      separation conditions, SPME-OPP-MS can be employed to quantify non-resolved
      compounds or those otherwise hindered by co-extracted isobaric interferences
      without further need of coupling to other separation platforms.

PMID- 29031303
TI  - Current advances and challenges in microfluidic free-flow electrophoresis-A
      critical review.
AB  - The research field on microfluidic free-flow electrophoresis has developed vast
      amounts of devices, methods, applications and raised new questions, often in
      analogy to conventional techniques from which it derives. Most efforts have been
      employed on device development and a myriad of architectures and fabrication
      techniques have been reported using simple proof-of-principle separations. As
      technological aspects reach a quite mature state, researchers' new challenges
      include the development of protocols for the separation of complex mixtures, as
      required in the fields of application. The success of this effort is extremely
      dependent on the capability to transfer the device's fabrication to an industrial
      setting as well as to ensure interfacing simplicity, namely at the solutions'
      supply and collection, and actuation such as electric potential application and
      temperature control. Other advanced applications such as direct interfacing to
      downstream systems such as mass spectrometry, integration of sensing and feedback
      controls will require further development in the laboratory. In this review we
      provide an overview on the field, from basic concepts, through advanced
      developments both in the theoretical and experimental arenas, and addressing the
      above details. A comprehensive survey of designs, materials and applications is
      presented with particular highlights to most recent developments, namely the
      integration of electrodes, flow control and hyphenation of microfluidic free-flow
      electrophoresis with other techniques.

PMID- 29031304
TI  - Coupling of the ring-oven-based preconcentration technique and surface-enhanced
      Raman spectroscopy: Application for the determination of purine bases in DNA.
AB  - In this paper, we present the advantages and limitations of the coupling of a
      ring-oven-based preconcentration technique and surface-enhanced Raman
      spectroscopy (SERS). Three different methods to promote analyte adsorption on
      gold nanoparticles using crystal violet as a probe molecule were assessed. The
      results showed significant improvements in sampling process, selectivity,
      sensitivity, repeatability (less than +/- 10%), and detection limits (nanomolar
      level) using a sample volume as small as 300 MUL. Finally, the standard addition
      method was successfully applied to the quantitative SERS detection of adenine and
      guanine in calf thymus DNA after ring-oven preconcentration with a calculated
      value of (G + C)/(A + T) close to the literature value. This work could therefore
      pave the way to quantifying a wide variety of biologically relevant compounds in
      real-world samples via the use of a biodegradable, low-cost and disposable paper
      platform for SERS.

PMID- 29031305
TI  - Do cancer patients with high levels of distress benefit more than less distressed
      patients from outpatient art therapy?
AB  - PURPOSE: Several studies have evaluated the effectiveness of art therapy for
      cancer patients. Our aim was to determine the effects of outpatient art therapy
      on the quality of life (QoL) of highly vs. less distressed cancer patients.
      METHODS: Participants completed the EORTC QLQ-C30 to measure QoL and the HADS to
      measure distress level before the intervention (t1), after completing the
      intervention (t2), and 6-months after t2 (t3). We performed analyses of
      covariance with repeated measures to test for group differences (highly vs. less
      distressed). We determined clinically relevant change scores and effect sizes in
      QoL domains (t1-t2; t1-t3) in patients with low vs. high levels of distress.
      RESULTS: 53 patient's participated at all three measuring points. Less (N = 22)
      vs. highly distressed patients (N = 31) differed at baseline and follow-up in
      their global QoL (mean t1:64.0 > 44.6; t2:65.5 > 55.6; t3:66.0 > 51.6; p = 0.01),
      emotional functioning (t1:65.2 > 37.4; t2:69.3 > 44.6; t3:57.8 > 48.5; p = 0.01),
      social functioning (t1:65.2 > 41.9; t2:77.3 > 52.7; t3:73.5 > 54.3; p = 0.01),
      cognitive functioning (t1:76.5 > 57.5; t2:74.4 > 62.4; t3:77.3 > 62.9; p = 0.02).
      There was no evidence of changes in physical functioning, role functioning,
      fatigue, pain, or insomnia. Interactions between distress, QoL, and time were not
      found. Effect sizes for clinical changes in QoL were medium regarding role
      functioning (Difft1-t3 = -14.4), fatigue (Difft1-t3 = -12.6) in the total group
      as well as in highly and less distressed patients. CONCLUSION: No evidence of
      outpatient art therapy having an effect on QoL in cancer patients over time was
      found, in patients with either high or low levels of distress at baseline.
      Consequently, it remains unclear which patients benefit the most from art
      therapy.

PMID- 29031306
TI  - Everyday life after a radical prostatectomy - A qualitative study of men under 65
      years of age.
AB  - PURPOSE: The purpose of this study was to illuminate how men under 65 years of
      age experience their everyday Life one year or more after a radical prostatectomy
      for localised prostate cancer. METHOD: Interviews with 19 men aged under 65 were
      performed 12-18 months after their radical prostatectomy. The interviews were
      analysed using a thematic content analysis. RESULTS: The analysis of the
      interviews revealed three categories of experiences: 'Paying a price for
      survival', 'Feeling sidestepped' and 'Living with death lurking around the
      corner'. The side effects of the prostatectomy, such as sexual dysfunction,
      resulted in a changed self-image with a loss of manliness and reduced self
      esteem. The men felt sidestepped and that they did not receive enough support.
      Prostate cancer was experienced as an embarrassing disease and the men felt their
      fundamental needs could not be openly discussed. Having cancer was associated
      with death. Thoughts about death faded away during recovery after the operation,
      but grew stronger in certain situations and reminded the men about their cancer.
      Returning to work and to previous activities helped them cope with the thoughts
      about death. CONCLUSIONS: Our study suggests a need for improved rehabilitation
      after a radical prostatectomy, including more structured sexual rehabilitation,
      and involving the partner. Sharing the experiences of other men who have
      undergone prostate cancer surgery may also be beneficial.

PMID- 29031307
TI  - Emotional concerns and coping strategies in Low Grade Glioma patients and
      reliability of their caregivers in reporting these concerns: Findings from a
      cross-sectional study.
AB  - PURPOSE: To explore the emotional concerns and coping strategies of patients with
      Low Grade Glioma (LGG) and whether or not their caregivers are reliable in
      reporting these concerns as surrogate informants. METHODS: An explorative cross
      sectional study. Patients who had undergone a neurosurgical procedure at least
      one year before this study for LGG and who were capable of participating in a
      face-to-face interview were included. Each patient nominated a reference
      caregiver. Both the patient and the caregiver were interviewed independently,
      using the Beck Depression Inventory Scale, the State - Trait Anxiety Inventory,
      and the Jalowiec Coping Scale. MAIN RESULTS: Forty-six patients and 46 caregivers
      were included. The average scores of the Beck scale were homogeneous between
      patients and caregivers (7.76 [CI 95% 5.76-9.75] vs. 6.23 [CI 95% 4.57-7.90]; p =
      0.102). Patients reported significantly greater state and trait anxiety (44.26
      [CI 95% 40.21-48.31] and 37.95 [CI 95% 34.97-40.94]), respectively compared to
      their caregivers (40.28 [CI 95% 36.64-43.91] and 35.17 [CI 95% 32.16-38.18]). The
      coping strategies enacted were homogeneous between patients and caregivers (82.78
      [CI 95% 77.21-88.35] vs (80.93 [CI 95% 76.32-85.55]; p = 0.102) while the kind of
      strategies adopted were significantly diverse. CONCLUSIONS: Patients suffer from
      depression and greater state anxiety as compared to trait anxiety; moreover, they
      enact less than half of the available coping strategies. Caregivers may be
      involved as surrogate informants when necessary for health-care professionals to
      detect depression while more caution is advised for what concerns anxiety and the
      coping strategies enacted by patients.

PMID- 29031308
TI  - Quality of life among Korean gastrointestinal cancer survivors.
AB  - PURPOSE: The number of gastrointestinal (GI) cancer survivors has been steadily
      increasing owing to early diagnosis and improved cancer treatment outcomes. The
      quality of life (QoL) of cancer survivors can provide distinct prognostic
      information and represent their functioning. This study aimed to investigate the
      levels of symptoms, psychological distress, and QoL of GI cancer survivors, and
      identify factors associated with QoL. METHOD: A cross-sectional survey was
      conducted among 145 survivors of gastric or colorectal cancer in a university
      affiliated hospital, Seoul, South Korea. The questionnaire consisted of the M. D.
      Anderson Symptom Inventory Gastrointestinal Cancer Module, Distress Thermometer,
      and brief version of the World Health Organization Quality of Life Assessment
      Instrument. Quantile regression was used to assess the associated factors of QoL.
      The 10th, 25th, 50th, 75th, and 90th conditional quantiles were considered.
      RESULTS: The most common symptoms were fatigue (24.9%), numbness or tingling
      (17.2%), feeling bloated (17.2%), dry mouth (15.9%), and difficulty remembering
      (11.8%). Thirty-two percent (47/145) of the participants reported severe
      distress. A level of symptoms was significantly associated in the 10th and 25th
      quantiles, representing poor QoL. Economic burden was a significant influencing
      factor in all quantiles. CONCLUSION: Our results indicate that high burden from
      symptoms might be associated with lower QoL in GI cancer survivors, and higher
      economic burden from cancer treatment was associated with lower QoL. These
      results suggest that symptom management and support for economic difficulties
      should be included in the strategies to enhance the QoL of GI cancer survivors.

PMID- 29031309
TI  - Measuring family needs of people living with cancer. Portuguese validation and
      descriptive studies of the Family Inventory of Needs.
AB  - PURPOSE: The aim of this study was to validate the Portuguese version of the
      Family Inventory of Needs (FIN). The FIN aims to measure important family needs
      and their fulfilment by a healthcare team. METHODS: This cross-sectional study
      involved a sample of 364 family members of cancer patients, recruited from three
      medical institutions and through online recruitment. Three instruments were used:
      a socio-demographic questionnaire, the FIN and the Brief Symptom Inventory - 18
      (BSI-18). Construct validity and reliability were considered regarding the FIN's
      psychometric properties. The method used to determine construct validity was
      factor structure analysis (confirmatory factor analysis), inter-factor
      correlations (Spearman's rank correlation) and convergent validity (Spearman's
      rank correlation). To assess scale reliability, the FIN's internal consistency
      was evaluated (Cronbach's alpha coefficient). Descriptive and frequency
      statistics and tests to compare means were used to assess important needs and to
      what extent they were met. RESULTS: The four-factor structure of the FIN was
      confirmed. Thus, the FIN has four domains: Basic Information, Information on
      treatment and care, Support and Patient Comfort. Convergent validity with the BSI
      18 was verified. Both subscales of the FIN and each domain exceeded the minimum
      reliability standard of 0.70. Family members also reported important needs that
      were not adequately met by healthcare professionals. CONCLUSIONS: The Portuguese
      version of the FIN seems to be a reliable and valid tool for identifying cancer
      patients' important family needs and to what extent these are met.

PMID- 29031310
TI  - In a bad place: Carers of patients with head and neck cancer experiences of
      travelling for cancer treatment.
AB  - PURPOSE: To explore the effect that treatment-related commuting has on carers of
      patients with head and neck cancer. METHOD: Semi-structured interviews,
      thematically analysed, with 31 carers. RESULTS: Treatment-related commuting had a
      considerable impact on carers of patients with head and neck cancer, both in
      practical terms (economic costs, disruption) and also in psychological terms.
      Many carers of patients with head and neck cancer described becoming distressed
      by their commute. Some carers from large urban cities appeared to have hidden
      commuting burdens. Some carers respond to commuting stress by 'zoning out' or
      becoming 'like zombies'. CONCLUSIONS: Treatment-related travel for head and neck
      cancer can have significant practical and psychological impacts. Health
      professionals should be aware of the impacts that commuting can have on head and
      neck caregivers. Health services may be able to take practical steps, such as
      providing subsidized parking, to address head and neck carergivers' difficulties.

PMID- 29031311
TI  - Nurses' perceptions of providing psychosexual care for women experiencing
      gynaecological cancer.
AB  - PURPOSE: To gain insight into how Western Australian nurses conceptualise the
      provision of psychosexual care for women undergoing gynaecological cancer
      treatment and how this aligns with nurses globally. METHODS: A qualitative
      descriptive design was chosen to facilitate insight into nurses' perspectives of
      their reality. Seventeen nurses working at a tertiary women's hospital in Western
      Australia participated in one-on-one interviews and were asked to describe their
      perceptions and identify factors that facilitate or challenge psychosexual care
      provision. RESULTS: Data analysis revealed five themes affecting the provision of
      psychosexual care: (1) Nurses use strategies to aid the conversation (subthemes:
      supporting the woman, facilitating engagement); (2) Women have unique
      psychosexual needs (subthemes: diversity, receptiveness); (3) Nurses are
      influenced by personal and professional experience and values (subthemes:
      confidence, values, making assumptions); (4) Systems within the health service
      affect care (subthemes: being supported by the system, working as a team); and
      (5) Society influences attitudes around sexuality. Nurses' views differed around
      whether these factors had a positive or negative impact on the conversation
      required to provide this care. CONCLUSIONS: Factors influencing nurses' provision
      of psychosexual care are multifaceted and differ amongst nurses. Recommended
      strategies to improve service provision include guidelines and documentation to
      integrate assessment of psychosexual issues as standard care, encouraging shared
      responsibility of psychosexual care amongst the multidisciplinary team and
      implementing education programs focussed on improving nurses' confidence and
      communication skills.

PMID- 29031312
TI  - Coping strategies of children treated for leukemia in China.
AB  - PURPOSE: To describe the coping strategies and preferred coping style of Chinese
      children with leukemia during hospitalization. METHODS: In-depth interview with a
      semi-structured interview were conducted with 29 Chinese children who underwent
      leukemia treatment. The Kippendorf's content analysis method was used to data
      analysis. RESULTS: During the hospitalization, children had three ways of
      psychological adjustment: Self-regulation, assistance of health professionals,
      helping of parents. There were many coping strategies. Problem-focused coping
      included seeking information and problem solving, and emotion-focused coping
      included seek emotional support, self-control, acceptance, seeking other rewards.
      CONCLUSIONS: Children use different coping styles consistent with their cognitive
      development stage, and Chinese traditional culture affects children's coping
      strategies.

PMID- 29031313
TI  - Routes to diagnosis for men with prostate cancer: men's cultural beliefs about
      how changes to their bodies and symptoms influence help-seeking actions. A
      narrative review of the literature.
AB  - PURPOSE: To examine the findings of existing studies in relation to men's
      cultural beliefs about changes to their bodies relevant to prostate cancer and
      how these affect interpretation of bodily changes and help-seeking actions.
      METHOD: We undertook a narrative review of studies conducted from 2004 to 2017 in
      6 databases that highlighted men's beliefs and help-seeking actions for bodily
      changes suggestive of prostate cancer. RESULTS: Eighteen (18) studies reflecting
      men from various ethnicities and nationalities were included. The belief that
      blood and painful urination were warning signs to seek medical help delayed help
      seeking among men compared to men that did not experience these symptoms. The
      belief that urinary symptoms such as dribbling, cystitis and urinary hesitancy
      were transient and related to ageing, normality and infection significantly
      delayed symptom appraisal and help-seeking. Men also held the belief that sexual
      changes, such as impotence and ejaculation dysfunction were private, embarrassing
      and a taboo. These beliefs impeded timely help-seeking. Cultural beliefs,
      spirituality and the role of wives/partners were significant for men to help
      appraise symptoms as requiring medical attention thus sanctioning the need for
      help-seeking. CONCLUSIONS: This review underscores a critical need for further
      empirical research into men's beliefs about bodily changes relevant to prostate
      health and how these beliefs affect their interpretation of symptoms and
      subsequent help-seeking actions.

PMID- 29031314
TI  - Corrigendum to "Aiming for a holistic integrated service for men diagnosed with
      prostate cancer - Definitions of standards and skill sets for nurses and allied
      healthcare professionals" [Eur. J. Oncol. Nurs. 29 (2017) 31-38].

PMID- 29031315
TI  - Exploration of life experiences of positive growth in long-term childhood cancer
      survivors.
AB  - PURPOSE: The aim of this study was to explore experiences of positive growth in
      long-term childhood cancer survivors, from their perspective. METHODS: Fifteen
      long-term survivors of childhood cancer provided descriptions of their
      experiences. Data were collected through face-to-face interviews and the analysis
      was based on Giorgi's phenomenological research method. RESULTS: The analysis of
      positive growth experienced by long-term childhood cancer survivors revealed
      three themes: self-directed life, normalcy in life, and inner maturity. Long-term
      survivors defined positive growth as a successful transition to a self
      satisfactory life based on motivation acquired through their cancer experience
      and on subjective goal-setting, as well as becoming cancer-free and living a
      normal life within society. They seemed to have acquired optimistic, flexible,
      active attitudes toward life while demonstrating profound gratefulness and
      consideration of people around them, as well as prudent approaches to health.
      CONCLUSIONS: The findings of this study verified that long-term survivors of
      childhood cancer have grown positively due to their negative past experience. We
      expect these findings to contribute to the development of programs that promote
      positive growth in long-term childhood cancer survivors.

PMID- 29031316
TI  - Identifying the unmet supportive care needs, with concomitant influencing
      factors, in adult acute leukemia patients in China.
AB  - PURPOSE: To understand the supportive care needs (SCNs), with associated
      influencing factors, related to five unmet need dimensions in adult Acute
      Leukemia (AL) patients, in China. METHODS: This multi-center cross-sectional
      study enrolled 340 pathologically confirmed adult, Chinese AL patients who were
      requested to complete a self-reported questionnaire, detailing demographic
      information, general status and physical functions, and Supportive Care Needs
      Survey-Short Form 34 (SCNS-SF34), revealing their unmet SCNs. The variables were
      statistically analyzed. RESULTS: A total of 311 (91.4%) effective questionnaires
      were retrieved. Among the 5 dimensions, the health information dimension scored
      the highest, 47.72(43.18), followed by psychological dimension, 35.00(32.50),
      while the sexual need scored the lowest, 0.00(24.99). As per multiple stepwise
      regression analysis, marital status, treatment stages and Karnofsky Performance
      Status index (KPS) score significantly influenced the health information
      dimension, while the age and "whether the treatment was the initial one or not"
      influenced sexual need dimension. KPS score and income were the common factors
      influencing the rest of the three dimensions with treatment stage adding to two
      of them except "physiological and daily living needs" dimension. "Being informed
      about your test results as soon as possible", "Being informed about things you
      can do to help yourself to get well" and "Being informed about cancer which is
      under control or in remission" were the three highest scoring entries.
      CONCLUSIONS: The results of this study reveal the unmet SCN's, with its
      influencing factors, in AL patients, the understanding of which may be of
      assistance in designing/delivering effective clinical nursing intervention.

PMID- 29031317
TI  - Emotional state and psychological flexibility in breast cancer survivors.
AB  - PURPOSE: This study analyses the premise that less time spent carrying out
      valuable activities and inflexible avoidance of thoughts, feelings and memories
      related to the oncological process may play an important role in the emotional
      problems of cancer survivors. METHODS: Emotional state was evaluated, as was
      quality of life and psychological flexibility in a sample of 122 breast cancer
      survivors (Mage = 52.40; SDage = 7.26). The analysis was carried out using a
      cross-sectional predictive study. RESULTS: Approximately half of those in the
      sample suffered from clinically significant emotional distress. The predictor
      variables selected explained a high percentage of the variability in emotional
      problems and quality of life (51.10-77.10%). CONCLUSION: Avoidance explained a
      high percentage of the variance in anxiety, depression and general distress. A
      lower degree of participation in valuable activities contributed, more
      specifically, to explaining variability in depression. The quantity and
      availability of environmental reinforcement was closely related to quality of
      life. A decisive contribution towards promoting emotional well-being and quality
      of life can be made by nursing action aimed at diminishing those avoidance
      strategies related to the oncological experience which may distance patients from
      daily activities which are gratifying and congruent with their values.

PMID- 29031318
TI  - Symptom clustering and quality of life in patients with ovarian cancer undergoing
      chemotherapy.
AB  - PURPOSE: The symptom clusters in patients with ovarian cancer undergoing
      chemotherapy have not been well evaluated. We investigated the symptom clusters
      and effects of symptom clusters on the quality of life of patients with ovarian
      cancer. METHOD: We recruited 210 ovarian cancer patients being treated with
      chemotherapy and used a descriptive cross-sectional study design to collect
      information on their symptoms. To determine inter-relationships among symptoms, a
      principal component analysis with varimax rotation was performed based on the
      patient's symptoms (fatigue, pain, sleep disturbance, chemotherapy-induced
      peripheral neuropathy, anxiety, depression, and sexual dysfunction). RESULTS: All
      patients had experienced at least two domains of concurrent symptoms, and there
      were two types of symptom clusters. The first symptom cluster consisted of
      anxiety, depression, fatigue, and sleep disturbance symptoms, while the second
      symptom cluster consisted of pain and chemotherapy-induced peripheral neuropathy
      symptoms. Our subgroup cluster analysis showed that ovarian cancer patients with
      higher-scoring symptoms had significantly poorer quality of life in both symptom
      cluster 1 and 2 subgroups, with subgroup-specific patterns. The symptom clusters
      were different depending on age, age at disease onset, disease duration,
      recurrence, and performance status of patients with ovarian cancer. In addition,
      ovarian cancer patients experienced different symptom clusters according to
      cancer stage. CONCLUSIONS: The current study demonstrated that there is a
      specific pattern of symptom clusters, and symptom clusters negatively influence
      the quality of life in patients with ovarian cancer. Identifying symptom clusters
      of ovarian cancer patients may have clinical implications in improving symptom
      management.

PMID- 29031319
TI  - Predictors of health-related quality of life in Korean prostate cancer patients
      receiving androgen deprivation therapy.
AB  - PURPOSE: We aimed to examine the level of psychological distress, fatigue, and
      health-related quality of life (HRQOL) and identify HRQOL predictors in men with
      prostate cancer receiving androgen deprivation therapy (ADT). METHODS: Using a
      cross-sectional design, we recruited 161 men with prostate cancer receiving ADT
      (mean age, 73 years) at two university-based hospitals in South Korea.
      Participants completed a self-reported questionnaire. Measures included the
      Hospital Anxiety and Depression Scale (HADS), the Functional Assessment of
      Chronic Illness Therapy-Fatigue (FACIT-F) subscale, and the Functional Assessment
      of Cancer Therapy-Prostate (FACT-P). RESULTS: The mean scores were 3.3 (SD = 2.8)
      for anxiety with a prevalence of 8.9%, 5.7 (SD = 3.8) for depression with a
      prevalence of 25.5%, and 30.3 (SD = 7.4) for fatigue with a prevalence of 15.6%.
      The five FACT-P subscale means were 23.9 (SD = 4.3) for physical well-being, 15.4
      (SD = 6.4) for social well-being, 18.5 (SD = 4.3) for emotional well-being, 17.3
      (SD = 5.6) for functional well-being, and 30.3 (SD = 7.4) for the prostate cancer
      specific subscale. Multiple linear regression analysis revealed that depression,
      which was inversely associated with all FACT-P subscales, was the strongest
      predictor of worse HRQOL. Fatigue and comorbid conditions were also associated
      with the HRQOL of multiple domains. CONCLUSION: This study suggests that
      intervention aimed at improving HRQOL of men receiving ADT should include
      depression, fatigue, and comorbidity management.

PMID- 29031320
TI  - Burnout and its relationship with personality factors in oncology nurses.
AB  - PURPOSE: To assess burnout levels in oncology nurses, to evaluate at what stage
      of burnout suffering they are and to analyze the relationship between burnout
      with personality factors. METHOD: A quantitative, observational, cross-sectional
      multicenter study was done. Oncology nurses (n = 101) from the Andalusian Health
      Service (Andalusia, Spain) were included. The main variables were personality
      factors, assessed with the NEO-FFI questionnaire, anxiety and depression,
      assessed with the Educational-Clinical Questionnaire: Anxiety and Depression, and
      burnout, evaluated with the Maslach Burnout Inventory. Student t-statistic was
      used for hypothesis contrasts and Pearson's correlation coefficient was used to
      establish the association between personality factors and burnout. RESULTS:
      According to the burnout phases model, 29.6% of the sample is in the most severe
      phases. Emotional exhaustion and depersonalization are positively correlated with
      neuroticism and negatively correlated with agreeableness, conscientiousness,
      extraversion and openness. Personal accomplishment has a negative correlation
      with neuroticism and negative correlations with agreeableness, conscientiousness,
      extraversion and openness. Finally, emotional exhaustion and depersonalization
      have a positive correlation with anxiety and depression, while personal
      accomplishment has a negative correlation with anxiety and depression.
      CONCLUSIONS: A significant number of oncology nurses are in the most severe
      stages of burnout suffering. Personality factors have a key role in burnout
      development. The importance of personality factors in burnout development should
      be taken into account.

PMID- 29031322
TI  - Cultural Factors in Ethics Consultations.

PMID- 29031321
TI  - Patients' experience of decision-making and receiving information during
      radiation therapy: A qualitative study.
AB  - PURPOSE: This study aimed to explore: (i) patient perceptions of how they are
      involved in treatment decisions about radiation therapy; (ii) patient knowledge
      and understanding of treatment; and (iii) what patients value in their
      interactions with the radiation therapy treatment team. METHOD: Patients were
      recruited through radiation oncology departments at metropolitan hospital sites
      located in Sydney, New South Wales, Australia. Semi-structured interviews were
      conducted with 21 radiation therapy patients with different types of cancer. Data
      were analysed using a Framework analysis to compare and contrast patient
      experiences. RESULTS: Most patients perceived the decision to undergo radiation
      therapy as agreeing to radiation oncologists recommendations rather than making a
      choice, but they trusted their radiation oncologist and were happy to follow
      their advice. Only a few participants reported their radiation oncologist had
      explained why radiation therapy was recommended, or discussed the benefits and
      harms. Some participants did not feel prepared for the intensity and disruption
      of side effects, and conveyed uncertainty about their diagnosis and the potential
      risk of recurrence. Most patients, irrespective of their type of cancer, valued
      the treatment team showing a genuine interest in how the treatment was effecting
      them, and being made to feel part of the department. CONCLUSION: Greater
      opportunities are needed to empower patients to ask questions about their
      uncertainties and concerns. Improvements in these areas will benefit patients and
      enable them to feel better prepared and know what to expect before and after
      their treatment.

PMID- 29031323
TI  - RE: Julie K. Silver, et al, Female Physicians Are Underrepresented in Recognition
      Awards from the AAPM&R.

PMID- 29031324
TI  - Thoroughbred fatality and associated jockey falls and injuries in races in New
      South Wales and the Australian Capital Territory, Australia: 2009-2014.
AB  - Monitoring racehorse fatality and associated jockey falls provides benchmarks for
      intervention strategies. The aims of this study were to describe the incidence of
      and reasons for fatalities in Thoroughbred horses during flat races in the
      Australian Capital Territory and New South Wales (NSW), Australia, and to
      describe reported jockey falls and injuries associated with racehorse fatalities.
      A cohort study identified all racehorse fatalities reported through Racing NSW
      for the 2009-2010 to 2013-2014 racing seasons. Risks of racehorse fatality, fatal
      musculoskeletal injury, spontaneous death (as distinct from euthanasia) and
      racehorse fatality associated jockey falls and injuries were calculated using
      Poisson regression. A total of 167 horse fatalities were reported, with an
      overall incidence of 0.59 deaths/1000 starts. Forty-nine reasons for horse
      fatality were reported, although post-mortem examinations were conducted on only
      52/165 (31.5%) horses. Musculoskeletal injury accounted for 144/167 (86.2%)
      fatalities, with an incidence of 0.52/1000 starts. Fractures comprised 96/167
      (57.5%) fatalities, with the fetlock or proximal sesamoid bones being the most
      common fracture location, comprising 36/96 (37.5%) fractures. Only 22/166 (13.3%)
      racehorse fatalities were due to spontaneous death, representing an incidence of
      0.08/1000 starts. A total of 50 racehorse fatality associated jockey falls were
      reported (incidence of 0.18/1000 starts), with 32 reported jockey injuries
      (incidence of 0.12/1000 starts). Most racehorse fatality associated jockey
      injuries occurred to the limbs (17/32, 53.1%), particularly the upper limb. The
      estimates for both horse fatality and associated jockey injury were comparable
      with previous estimates from other jurisdictions internationally.

PMID- 29031325
TI  - An observational study of the relationship between Capacity for Care as an animal
      shelter management model and cat health, adoption and death in three animal
      shelters.
AB  - Animal shelters struggle to function at their 'right size' in terms of physical,
      staffing and outcome capacity, especially with seasonal fluctuations in cat
      intake. To address this, a Capacity for Care (C4C) management model was devised
      to balance health and welfare requirements of all animals while maintaining or
      improving goals for positive outcomes, such as adoption or transfer. In this
      observational study of three shelters, applying the C4C management system gave
      each organization an optimal average daily shelter cat population target (to be
      achieved through proactive length of stay management) and helped each shelter to
      increase the size of their feline housing units. Pre- and post-C4C implementation
      data were evaluated to determine impact on average monthly isolation ward
      populations and cat outcomes such as adoptions and shelter deaths
      (euthanasia/died). Improved outcomes including increased adoption probability,
      decreased shelter death probability and fewer cats requiring infectious disease
      isolation were seen after C4C institution. Results suggest that implementation of
      this management model could help other shelters achieve similar results.

PMID- 29031326
TI  - Triglyceride concentrations in neonatal foals: Serial measurement and effects of
      age and illness.
AB  - Few studies have evaluated the effects of age and illness on serum triglyceride
      concentrations in neonatal foals. The objectives of this study were to evaluate
      triglyceride concentrations in neonatal foals and their dams through serial
      measurement immediately postpartum and at 1-2 days and 10-12 days of age, as well
      as to measure them in sick foals. Serially measured serum triglycerides in seven
      healthy foals varied with age. Median (range) triglyceride concentrations were
      28mg/dL (12-50mg/dL), 89mg/dL (51-264mg/dL), and 60mg/dL (28-135mg/dL)
      immediately postpartum, at 1-2 days of age, and 10-12 days of age, respectively
      (P<0.001). Triglyceride concentrations varied hourly by up to 117mg/dL in
      individual foals. The dams had lower triglycerides (median, 20mg/dL; range, 12
      49mg/dL) than the foals, once foals were >24h old. Sick foals <24h old had lower
      triglycerides than sick foals aged 1-7 days (median, 41mg/dL [range, 16-116];
      median, 110mg/dL [range, 24-379mg/dL]; P<0.001). Age and triglyceride
      concentration showed a non-linear association independent of foal health status
      (P=0.01). Sick foals with positive bacterial cultures had higher triglycerides
      than those with negative cultures (median, 111mg/dL [range, 10-379mg/dL] and
      median 53mg/dL [range, 17-271mg/dL], respectively; P=0.033). Nonsurvivors had
      higher triglycerides than survivors (median, 116mg/dL [range, 41-379mg/dL] and
      median, 55mg/dL [range, 10-311mg/dL], respectively; P=0.04). In conclusion,
      triglycerides were highest in healthy neonatal foals aged 1-2 days, and in
      nonsurviving sick foals and those with positive bacterial cultures. Age was
      associated with triglyceride concentration regardless of health status.

PMID- 29031327
TI  - Respiratory variation in aortic blood peak velocity and caudal vena cava diameter
      can predict fluid responsiveness in anaesthetised and mechanically ventilated
      dogs.
AB  - BACKGROUND AND M&MS: Dynamic preload indices, such as systolic pressure variation
      (SPV), aortic flow peak velocity variation (DeltaVpeak) and distensibility index
      of the caudal vena cava (CVCDI), are reliable indices for predicting fluid
      responsiveness in humans. This study aimed to investigate the ability of these
      indices to predict fluid response in 24 healthy dogs undergoing general
      anaesthesia and mechanical ventilation. Aortic flow peak velocity variation
      (?Vpeak), CVCDI, and SPV were calculated before volume expansion (5mL/kg bolus of
      lactated Ringer's solution). The aortic velocity time integral (VTI) was measured
      before and after volume expansion as a surrogate of stroke volume. Dogs were
      considered responders (n=9) when the VTI increase was >=15% and non-responders
      (n=15) when the increase was <15%. RESULTS AND CONCLUSIONS: Before volume
      expansion, DeltaVpeak, CVCDI and SPV were higher in responders than in non
      responders (P=0.0009, P=0.0003, and P=0.0271, respectively). Receiver operating
      characteristic (ROC) curves were plotted for the three indices. The areas under
      the ROC curves for SPV, DeltaVpeak, and CVCDI were 0.91 (CI 0.73-0.99; P=0.0001),
      0.95 (CI 0.77-1; P=0.0001), and 0.78 (CI 0.56-0.92; P=0.015), respectively. The
      best cut-offs were 6.7% for SPV (sensitivity, 77.78%; specificity, 93.33%), 9.4%
      for DeltaVpeak (sensitivity, 88.89%; specificity, 100%), and 24% for CVCDI
      (sensitivity, 77.78%; specificity, 73.33). In conclusion, DeltaVpeak, CVCDI, and
      SPV are reliable predictors of fluid responsiveness in healthy dogs undergoing
      general anaesthesia and mechanical ventilation.

PMID- 29031328
TI  - Minimally invasive wireless motility capsule to study canine gastrointestinal
      motility and pH.
AB  - The aim of this study was to describe the feasibility of using a gastrointestinal
      tract wireless motility capsule (WMC) that measured intraluminal pressure, pH and
      transit time through the gastrointestinal tract, in dogs in their home
      environment. Forty-four adult healthy dogs, eating a standard diet, were
      prospectively enrolled. The WMC was well tolerated by all dogs and provided data
      from the different sections of the gastrointestinal tract. Median gastric
      emptying time was 20h (range, 6.3-119h), demonstrating a large range. The gastric
      pressure pattern and pH depended on the phase of food consumption. The small
      bowel transit time was 3.1h (range, 1.6-5.4h) with average contraction pressures
      of 6.5mmHg (range, 1.1-21.4mmHg) and pH 7.8 (range, 7-8.9). The large bowel
      transit time was 21h (range, 1-69h) with average contractions pressures of
      0.9mmHg (range, 0.3-2.7mmHg) and pH 6.4 (range, 5.3-8.2). There was considerable
      individual variation in motility patterns and transit times between dogs. No
      difference was observed between the sexes. No relationships between any transit
      time, bowel pH or pressure pattern and bodyweights were identified. The WMC
      likely represents movement of a large non-digestible particle rather than normal
      ingesta. Due to its large size, the WMC should not be use in smaller dogs. The
      WMC is a promising minimally invasive tool to assess GIT solid phase transit
      times, pressures and pH. However, further studies are necessary due to the
      current limitations observed.

PMID- 29031329
TI  - Dogs with macroadenomas have lower body temperature and heart rate than dogs with
      microadenomas.
AB  - Pituitary macroadenomas compress the hypothalamus, which partly regulates heart
      rate and body temperature. The aim of this study was to investigate whether heart
      rate and/or body temperature could aid in clinically differentiating dogs with
      macroadenomas from dogs with microadenomas (i.e. small non-compressive pituitary
      mass). Two groups of dogs diagnosed with pituitary-dependent hyperadrenocorticism
      (i.e. Cushing's disease) were included. Heart rate and body temperature were
      collected on initial presentation before any procedure. Dogs with macroadenoma
      had a significantly lower heart rate and body temperature (P<0.01) compared to
      dogs with microadenoma. We suggest that the combined cut-off values of 84 beats
      per minutes and 38.3 degrees C in dogs with Cushing's disease, especially with
      vague neurological signs (nine of 12 dogs=75%), might help to suspect the
      presence of a macroadenoma.

PMID- 29031330
TI  - Histological changes in the proximal suspensory ligament after neurectomy of the
      deep branch of the lateral palmar nerve of horses with induced proximal
      suspensory desmitis.
AB  - Proximal suspensory desmitis (PSD) is a common cause of lameness in the pelvic
      limb, but could also affect the thoracic limb of competing and non-competing
      horses. Most horses diagnosed with PSD in a thoracic limb respond to rest
      followed by controlled exercise, but in a small percentage of affected horses,
      lameness persists. In one study, four horses chronically lame because of PSD in a
      thoracic limb became sound after neurectomy of the deep branch of the lateral
      palmar nerve (DBLPaN), which innervates the proximal aspect of the suspensory
      ligament (SL; Guasco et al., 2013). Whether neurectomy of the DBLPaN results in
      changes in the SL that might predispose the horse to re-injury is not known. The
      aim of this study was to describe the findings observed during quantitative
      lameness evaluation, gross and histological examination of the proximal portion
      of the suspensory ligament (SL) of the thoracic limbs of eight horses after
      neurectomy of the DBLPaN performed after inducing unilateral PSD by injecting
      collagenase into the proximal portion of the SL. The clinical response to
      neurectomy was resolution of lameness in all horses. Muscle fibers of the
      denervated ligaments presented atrophy and were infiltrated with fat and
      connective tissue, thereby reducing the strength and elasticity of the ligament.

PMID- 29031331
TI  - Comparing subjective and objective evaluation of show jumping competition and
      warm-up arena surfaces.
AB  - The development of safety and quality standards for equestrian surfaces needs to
      be based on objective, repeatable measurements which allow comparisons between
      surfaces. These measurements should incorporate the assessment of surface
      performance by riders. This study provides data from objective and subjective
      assessment of functional properties of high-level show jumping competition and
      warm-up arenas. Twenty-five arenas in nine international show jumping events were
      evaluated by mechanical in-situ testing with a surface tester, rider assessments
      using visual analogue scales (198 riders provided 749 arena evaluations),
      descriptions of arena constructions and by laboratory tests of surface material.
      Mixed models were used to present subjective evaluation of rider perception of
      the functional properties for each arena while controlling for rider and event.
      The association between objective and subjective assessments were also explored
      creating mixed models, controlling for rider and event. Mechanical measurements
      of impact firmness, and to a lesser extent cushioning and grip, had a significant
      positive association with the riders' perception. Responsiveness as assessed by
      the Orono biomechanical surface tester (OBST) was negatively associated with the
      riders' perceptions, which suggests riders and the OBST had different concepts of
      this functional property and that further developments of the OBST might be
      necessary. Objectively measured uniformity showed no useful association with
      riders' perception. Even though arena assessments were made by top level riders,
      a substantial inter-rider variation was demonstrated.

PMID- 29031332
TI  - Right ventricular function during pharmacological and exercise stress testing in
      horses.
AB  - The disproportionate rise of pulmonary artery pressure compared to systemic blood
      pressure during exercise can lead to detrimental right ventricular remodelling in
      endurance athletes. Horses may act as an extreme model of these athletic
      cardiovascular adaptations, as they show a three fold increase in pulmonary
      pressures during exercise. Right ventricular function was examined in ten healthy
      horses using post-exercise and pharmacological stress echocardiography in a
      randomised cross-over design. Exercise testing was performed on a treadmill while
      pharmacological testing was performed using an atropine-dobutamine infusion.
      Heart rate, systemic blood pressure and cardiac output during echocardiography
      were similar post-exercise compared to maximal pharmacological stress. Systolic
      pulmonary artery pressure was significantly higher during the exercise test
      (121+/-15mmHg) and during immediate post-exercise echocardiography (93+/-10mmHg)
      compared to maximal pharmacological stress (69+/-12mmHg). Right ventricular
      diameters as well as the ratio of systolic right to left ventricular area were
      higher post-exercise. Right ventricular fractional area change was significantly
      decreased post-exercise (40.5+/-6.2%) compared to a significant increase during
      pharmacological stress echocardiography (72.6+/-7.3%). Serum cardiac troponin I
      concentration was significantly higher 2h after the pharmacological test compared
      to baseline values and post-exercise, although the highest value was found post
      exercise in the horse with the highest systolic pulmonary artery pressure and
      lowest right ventricular fractional area change. Pharmacological stress testing
      is not recommended in further studies on right ventricular adaptations in
      athletic horses, as this does not reproduce the effects of exercise.

PMID- 29031333
TI  - Benefits of Exercise in the Older Population.
AB  - Older adults 65 years of age and older compose a great portion of the US
      population. Physiologic changes of aging that limit function and general quality
      of life occur at a faster rate as we get older. There is high-quality evidence
      that exercise activity has many favorable benefits for older adults. The ideal
      exercise program in older adults should include aerobic, resistance, flexibility,
      and balance training. The exercise recommendations should be individually
      tailored to the abilities, precautions, and goals of each person. They also
      should be of sufficient intensity, volume, and duration in order to achieve
      maximal benefits.

PMID- 29031334
TI  - Alternative Treatment Modalities and Its Effect in Older Populations.
AB  - Aging is an inevitable multifactorial process. Advances in health care and
      technology have led to an increase on expected life span that can reach an
      average of 90 years in the next few decades. Lifestyle changes that include
      activity, nutrition, stress management, and alternatives low-impact exercises
      like yoga and tai chi can help us modify some of these age-related changes and
      lead to an increase in the health span and quality of life of the older adults.

PMID- 29031335
TI  - Can We Increase Our Health Span?
AB  - The deterioration of physical and mental capabilities is inevitable with aging.
      Some hereditary factors cannot be changed, but other external factors can be
      manipulated to provide our body with better weapons to improve quality of life as
      we age. Different cellular pathways leading to cell deterioration and aging
      usually act through excessive oxidative damage and chronic inflammation.
      Suppression of inflammation is the most important driver of successful longevity
      and increases in importance with advancing age. Modifying caloric intake, amount
      and type of food, and maintaining an active lifestyle can decrease the risk of
      most common chronic diseases of aging.

PMID- 29031336
TI  - Psychosocial Issues in Geriatric Rehabilitation.
AB  - Geriatric patients present multiple age-related challenges and needs that must be
      taken into account during the rehabilitation process to achieve expected goals.
      This article examines the importance of identifying and managing psychosocial
      issues commonly observed in older adults and presents strategies to optimize
      their rehabilitation process. Depression, anxiety, fear of falling, adjustment
      issues, neurocognitive disorders, and caregiver support are discussed as a
      selection of factors that are relevant for geriatric patients undergoing
      rehabilitation. An argument is made for the importance of comprehensive geriatric
      assessment in older adults to identify salient issues that may impact
      rehabilitation and quality of life.

PMID- 29031337
TI  - Physiologic Changes of the Musculoskeletal System with Aging: A Brief Review.
AB  - Aging is one of the important challenges of modern society. Advanced adult age is
      associated with changes in many physiologic systems. Of particular interest is
      the musculoskeletal system because it directly contributes to mobility and
      functional independence. Skeletal muscle mass and strength decline with age.
      These changes are mostly due to a reduction in the number of muscle fibers and
      cellular and molecular changes that reduce the force-generation process. Bone
      mass and architecture are compromised and may result in fractures. Tendons and
      ligaments undergo significant biochemical alterations that directly compromise
      their biomechanical function.

PMID- 29031338
TI  - Normal Changes in Gait and Mobility Problems in the Elderly.
AB  - There are normal physiologic changes that occur as people age. Gait and mobility
      are altered with aging, and these changes are a combination of alterations in the
      gait pattern and in the function of organs. Changes in gait are associated with
      functional decline, less independence, and impaired quality of life. Reduced
      walking speed is the most consistent age-related change, but there are other
      contributors to an altered gait: impaired balance and stability, lower extremity
      strength, and the fear of falling.

PMID- 29031339
TI  - Balance Problems and Fall Risks in the Elderly.
AB  - Falls in the elderly are an increasing problem causing a high degree of
      morbidity, mortality, and use of health care services. Identification of risk
      factors through medical assessment supports the provision of appropriate
      interventions that reduce rates of falling. Evaluation and intervention
      strategies are generally challenging because of the complex and multifactorial
      nature of falls. The clinician should consider screening for falls an important
      part of the functional evaluation in older adults. Several potential
      interventions have proven helpful as preventive strategies. Optimal approaches
      involve interdisciplinary collaboration in assessment and interventions,
      particularly exercise, attention to coexisting medical conditions, and reduction
      of environmental hazards.

PMID- 29031340
TI  - Clinical Pharmacology and the Risks of Polypharmacy in the Geriatric Patient.
AB  - Elderly people have several characteristics that make them unique. They have
      several factors such as environmental factors and demographic factors such as
      age, sex, socioeconomic level, and schooling, which contribute to these
      differences being accentuated. As one ages, these various organic and systemic
      features are accentuated. The pace varies between people, and organs and systems
      suffer from several normal and adverse changes that make them more or less
      susceptible to diseases and injuries, and the medications are responsible for
      many of these threats. This article raises awareness about these changes.

PMID- 29031341
TI  - Nutritional Needs of the Older Adult.
AB  - Older adults are particularly vulnerable to compromised nutritional status. With
      advancing age, the consumption of a high-quality, nutritionally dense diet is
      increasingly essential to optimize health and well-being. Proportionally,
      macronutrient needs for older adults are similar to younger adults, however
      overall calorie requirements tend to decline with age. Unique factors influencing
      food intake should be considered and individualized guidance should be designed
      to help overcome medical, physical, and social barriers to a healthy diet. The
      goal for nutrition intervention should ultimately be to promote health and
      quality of life across the continuum of the aging process.

PMID- 29031342
TI  - The Competitive Senior Athlete.
AB  - Clinicians should discuss common health issues of the older population and how
      medical problems affect their sports performance. Patients with chronic
      conditions, such as hypertension and diabetes mellitus, benefit from
      participation in sports. However, special care should be taken to keep the
      patient healthy and minimize effects of these conditions and their treatments in
      athletic performance. Another important consideration in the older athlete is
      fluid ingestion and the increased risk of dehydration. There is evidence that
      physical exercise reduces pain in osteoarthritis and enhances physical function
      of affected joints. Older athletes often use multiple medications and dietary
      supplements; Clinicians should educate patients about possible effects of
      medications in sports performance.

PMID- 29031343
TI  - Musculoskeletal Injuries and Regenerative Medicine in the Elderly Patient.
AB  - Regenerative medicine has gained increasing popularity in its clinical
      applications, particularly in the field of musculoskeletal medicine. Regenerative
      medicine, a broad term, can be thought of as a particular medical strategy that
      strives to rebuild and restore diseased tissue to normal physiologic tissue
      baseline. Simply put, regenerative strategies augment the body's innate
      physiology to heal pathologic processes. This article focuses on specific
      regenerative strategies and the uses of them for common pathologies in the aging
      adult, including platelet-rich plasma, mesenchymal stem cells,
      viscosupplementation, and prolotherapy.

PMID- 29031344
TI  - Clinical Considerations for the Use Lower Extremity Arthroplasty in the Elderly.
AB  - There is an increase in the aging population that has led to a surge of reported
      cases of osteoarthritis and a greater demand for lower extremity arthroplasty.
      This article aims to review the current treatment options and expectations when
      considering lower extremity arthroplasty in the elderly patient with an emphasis
      on the following subjects: (1) updated clinical guidelines for the management of
      osteoarthritis in the lower extremity, (2) comorbidities and risk factors in the
      surgical patient, (3) preoperative evaluation and optimization of the surgical
      patient, (4) surgical approach and implant selection, and (5) rehabilitation and
      life after lower extremity arthroplasty.

PMID- 29031345
TI  - Rehabilitation Needs of the Elderly Patient with Cancer.
AB  - Physiatrist taking care of the geriatric patient with cancer should be able to
      manage an array of conditions that might present from diagnosis throughout
      completion of treatments and beyond. The elderly cancer population is at greater
      risk of functional impairments. The physician should anticipate changes in
      clinical status and must adjust rehabilitation goals accordingly. Treatment
      options and rehabilitation goals should be tailored to help maximize quality of
      life in these patients.

PMID- 29031346
TI  - Aging with Spinal Cord Injury: An Update.
AB  - The 2016 National Spinal Cord Injury Statistical Center's Spinal Cord Injury
      (SCI) Facts and Figures reports approximately 17,000 new cases yearly,
      approximately 54 cases per million. The past 40 years has brought a significant
      change in patterns of injury. The average age has increased from 29 years in the
      1970s to approximately 42 years currently; it is believed it has plateaued. Aging
      persons with SCI may have a higher risk of developing other medical
      complications. Studies report a perceived improvement in quality of life among
      persons with SCI with age, influenced by psychological, medical, and
      environmental factors.

PMID- 29031347
TI  - Rehabilitation Needs of the Elder with Traumatic Brain Injury.
AB  - The incidence of traumatic brain injury (TBI) in older adults is increasing. As
      the expected life expectancy increases, there is a heightened need for
      comprehensive rehabilitation for this population. Elderly patients with TBI
      benefit from rehabilitation interventions at all stages of injury and can achieve
      functional gains during acute inpatient rehabilitation. Clinicians should be
      vigilant of unique characteristics of this population during inpatient
      rehabilitation, including vulnerability to polypharmacy, posttraumatic
      hydrocephalus, neuropsychiatric sequelae, sleep disturbances, and sensory
      deficits. Long-term care should include fall prevention, assessment of cognitive
      deficits, aerobic activity, community reintegration, and caretaker support. Life
      expectancy is reduced after TBI.

PMID- 29031348
TI  - Foreword.

PMID- 29031349
TI  - Aging with Grace, Dignity, and Courage: A Mission for Physical Medicine and
      Rehabilitation.

PMID- 29031350
TI  - Preface.

PMID- 29031351
TI  - Hyperkalemia: Inpatient PaniK.

PMID- 29031352
TI  - Disturbances in Acid-Base, Potassium, and Sodium Balance in Patients With CKD:
      New Insights and Novel Therapies.

PMID- 29031353
TI  - Regulation of Acid-Base Balance in Chronic Kidney Disease.
AB  - The kidneys play a major role in the regulation of acid-base balance by
      reabsorbing bicarbonate filtered by the glomeruli and excreting titratable acids
      and ammonia into the urine. In CKD, with declining kidney function, acid
      retention and metabolic acidosis occur, but the extent of acid retention depends
      not only on the degree of kidney impairment but also on the dietary acid load.
      Acid retention can occur even when the serum bicarbonate level is apparently
      normal. With reduced kidney function, acid transport processes in the surviving
      nephrons are augmented but as disease progresses ammonia excretion and, in some
      individuals, the ability to reabsorb bicarbonate falls, whereas titratable acid
      excretion is preserved until kidney function is severely impaired. Urinary
      ammonia levels are used to gauge the renal response to acid loads and are best
      assessed by direct measurement of urinary ammonia levels rather than by indirect
      assessments. In individuals with acidosis from CKD, an inappropriately low degree
      of ammonia excretion points to the pathogenic role of impaired urinary acid
      excretion. The presence of a normal bicarbonate level in CKD complicates the
      interpretation of the urinary ammonia excretion as such individuals could be in
      acid-base balance or could be retaining acid without manifesting a low
      bicarbonate level. At this time, the decision to give bicarbonate supplementation
      in CKD is reserved for those with a bicarbonate level of 22 mEq/L, but because of
      potential harm of overtreatment, supplementation should be adjusted to maintain a
      bicarbonate level of <26 mEq/L.

PMID- 29031355
TI  - Adverse Effects of the Metabolic Acidosis of Chronic Kidney Disease.
AB  - The kidney has the principal role in the maintenance of acid-base balance, and
      therefore, a fall in renal net acid excretion and positive H+ balance often
      leading to reduced serum [HCO3-] are observed in the course of CKD. This
      metabolic acidosis can be associated with muscle wasting, development or
      exacerbation of bone disease, hypoalbuminemia, increased inflammation,
      progression of CKD, protein malnutrition, alterations in insulin, leptin, and
      growth hormone, and increased mortality. Importantly, some of the adverse effects
      can be observed even in the absence of overt hypobicarbonatemia. Administration
      of base decreases muscle wasting, improves bone disease, restores responsiveness
      to insulin, slows progression of CKD, and possibly reduces mortality. Base is
      recommended when serum [HCO3-] is <22 mEq/L, but the target serum [HCO3-] remains
      unclear. Evidence that increments of serum [HCO3-] >26 mEq/L might be associated
      with worsening of cardiovascular disease adds complexity to treatment decisions.
      Further study of the mechanisms through which positive H+ balance in CKD
      contributes to its various adverse effects and the pathways involved in mediating
      the benefits and complications of base therapy is warranted.

PMID- 29031354
TI  - Epidemiology of Acid-Base Derangements in CKD.
AB  - Acid-base disorders are in patients with chronic kidney disease, with chronic
      metabolic acidosis receiving the most attention clinically in terms of diagnosis
      and treatment. A number of observational studies have reported on the prevalence
      of acid-base disorders in this patient population and their relationship with
      outcomes, mostly focusing on chronic metabolic acidosis. The majority have used
      serum bicarbonate alone to define acid-base status due to the lack of widely
      available data on other acid-base disorders. This review discusses the time
      course of acid-base alterations in CKD patients, their prevalence, and
      associations with CKD progression and mortality.

PMID- 29031356
TI  - Management of the Metabolic Acidosis of Chronic Kidney Disease.
AB  - Subjects with CKD and reduced glomerular filtration rate are at risk for chronic
      metabolic acidosis, and CKD is its most common cause. Untreated metabolic
      acidosis, even in its mildest forms, is associated with increased mortality and
      morbidity and should therefore be treated. If reduced glomerular filtration rate
      or the tubule abnormality causing chronic metabolic acidosis cannot be corrected,
      it is typically treated with dietary acid (H+) reduction using Na+-based alkali,
      usually NaHCO3. Dietary H+ reduction can also be accomplished with the addition
      of base-producing foods such as fruits and vegetables and limiting intake of H+
      producing foods like animal-sourced protein. The optimal dose of Na+-based alkali
      that prevents the untoward effects of metabolic acidosis while minimizing adverse
      effects and the appropriate combination of this traditional therapy with dietary
      strategies remain to be determined by ongoing studies. Recent emerging evidence
      supports a phenomenon of H+ retention, which precedes the development of
      metabolic acidosis by plasma acid-base parameters, but further studies will be
      needed to determine how best to identify patients with this phenomenon and
      whether they too should be treated with dietary H+ reduction.

PMID- 29031357
TI  - Regulation of Potassium Homeostasis in CKD.
AB  - Disturbances of potassium homeostasis can cause either hyperkalemia or
      hypokalemia and result in serious consequences. Although the consequences of
      acute and chronic hyperkalemia and treatment of these conditions in CKD have been
      widely appreciated by nephrologists, more recent information has focused
      attention on the consequences of chronic hypokalemia. Several recent studies have
      documented a "U-shaped" relationship between the serum [K+] and higher mortality
      in several clinical studies. The causes of dyskalemias are placed into the unique
      perspective of patients with CKD and its evolution with progression of CKD to
      later stages and focuses on the pathophysiology of these disorders. Emphasis is
      placed on the high mortality associated with both low and high levels of
      potassium that are unique to patients with CKD. Recent information regarding
      sensors of changes in the serum [K+] that evoke changes in NaCl transport in the
      DCT1 and subsequent efferent responses by aldosterone-responsive cells in the
      DCT2 and cortical collecting duct to adjust K+ secretion by the renal outer
      medullary potassium channel is reviewed in detail. These sensing mechanisms can
      be interrupted by drugs, such as the calcineurin inhibitors to cause both
      hypertension and hyperkalemia in kidney transplant patients, or can be inherited
      as familial hypertensive hyperkalemia. The role and pathogenesis of angiotensin
      converting enzyme inhibitors and angiotensin receptor blockers in causing
      hyperkalemia is a common stop point for cessation of these important drugs, but,
      and newer agents to lower the serum [K+] that might allow continuation of
      angiotensin-converting enzyme or angiotensin receptor blocker therapy are
      examined. Finally, the importance of emphasis on potassium-containing foods, such
      as fresh produce and fruit in the diets of patients with early-stage CKD, is
      examined as an under-appreciated area requiring more emphasis by nephrologists
      caring for these patients and may be unique to food-challenged patients with CKD.

PMID- 29031358
TI  - Hyperkalemia and Hypokalemia in CKD: Prevalence, Risk Factors, and Clinical
      Outcomes.
AB  - Abnormalities of serum potassium are common in patients with CKD. Although
      hyperkalemia is a well-recognized complication of CKD, the prevalence rates of
      hyperkalemia (14%-20%) and hypokalemia (12%-18%) are similar. CKD severity, use
      of medications such as renin-angiotensin-aldosterone system inhibitors and
      diuretics, and dietary potassium intake are major determinants of serum potassium
      concentration in CKD. Demographic factors, acid-base status, blood glucose, and
      other comorbidities contribute as well. Both hyperkalemia and hypokalemia are
      associated with similarly increased risks of death, cardiovascular disease, and
      hospitalization. On the other hand, limited evidence suggests a link between
      hypokalemia, but not hyperkalemia, and progression of CKD. This article reviews
      the prevalence rates and risk factors for hyperkalemia and hypokalemia, and their
      associations with adverse outcomes in CKD.

PMID- 29031359
TI  - Treatment of Abnormalities of Potassium Homeostasis in CKD.
AB  - Hyperkalemia, defined as serum potassium concentrations greater than 5.0 to 5.5
      mEq/L, is a frequent occurrence in clinical practice because of the increasing
      incidence and prevalence of CKD. Patients at risk for this disorder are commonly
      treated with drugs that interfere in the renin-angiotensin-aldosterone system,
      thereby enhancing the occurrence and prevalence of this disorder. Discontinuation
      of these drugs because of the development of hyperkalemia deprives these patients
      the renal-protective and cardiovascular benefits this class of pharmacology has
      been shown to provide. Here we provide the clinician strategies to both prevent
      and treat hyperkalemia in patients with CKD who are prescribed these drugs. We
      emphasize the importance of limiting dietary potassium intake and avoiding either
      prescribed or over-the-counter medications that may impair renal potassium
      excretion. We discuss the role of kaliuretic diuretics and correction of
      metabolic acidosis as a therapeutic strategy. Additionally, we discuss the role
      of new agents designed to bind potassium in the gastrointestinal tract that can
      be used to maintain normokalemia in patients who previously developed
      hyperkalemia on renin-angiotensin-aldosterone blockers. Finally, we provide a
      brief discussion on how best to treat hypokalemia in patients with CKD.

PMID- 29031360
TI  - Sodium Homeostasis in Chronic Kidney Disease.
AB  - The pathologic consequences of sodium retention in the CKD population can lead to
      hypertension, edema, and progressive disease. Sodium excess is responsible for
      increases in oxidative stress, which alters kidney vasculature. As progression of
      CKD occurs, hyperfiltration by remaining nephrons compensates for an overall
      decrease in the filtered load of sodium. In the later stages of CKD, compensatory
      mechanisms are overcome and volume overload ensues. Nephrotic syndrome as it
      relates to sodium handling involves a different pathophysiology despite a common
      phenotype. Extrarenal sodium buffering is also examined as it has significant
      implications in the setting of advanced CKD.

PMID- 29031362
TI  - Letter from the Guest Editor: Imaging of Lymph Nodes in the Head and Neck.

PMID- 29031363
TI  - Chapter 1 Neck Anatomy, Imaging-Based Level Nodal Classification and Impact of
      Primary Tumor Site on Patterns of Nodal Metastasis.
AB  - The anatomy of the neck is complex, with many critical structures crowded
      together in a relatively small cross-sectional area. Many structures in the neck
      also have similar soft tissue density or signal that further complicates
      interpretation for the radiologist, who relies on tissue differences to create
      contrast resolution and distinguish structures. Head and neck cancer incidence
      exceeds 550,000 cases per year worldwide, with diagnosis, treatment, and
      prognosis relying highly on a thorough knowledge of this compact space. This
      article focuses on reviewing head and neck anatomy with special attention to
      nodal anatomy and on discussing the expected patterns of nodal spread in head and
      neck cancers.

PMID- 29031361
TI  - Treatment of Disorders of Sodium Balance in Chronic Kidney Disease.
AB  - Extracellular fluid volume expansion is nearly universal in patients with CKD.
      Such volume expansion has features similar to the syndrome of heart failure with
      preserved ejection fraction, which not only leads to symptoms but can also lead
      to further organ damage. Unique treatment challenges are present in this patient
      population, including low glomerular filtration, which limits sodium chloride
      filtration, intrinsic tubule predisposition to sodium chloride retention, and
      proteinuria. In addition, pharmacokinetic considerations alter the disposition of
      diuretics in patients with CKD and nephrotic syndrome. Maintaining extracellular
      fluid volume near to normal is often necessary for hypertension treatment in this
      population, but it may also help prevent progressive cardiovascular and kidney
      damage. Although powerful diuretics can often accomplish this goal, this often
      comes at a cost of competing adverse effects. An approach to reduce extracellular
      fluid volume while avoiding adverse effects, therefore, requires a nuanced yet
      aggressive therapeutic approach.

PMID- 29031364
TI  - Chapter 2 Squamous Cell Carcinoma of the Head and Neck-Imaging Evaluation of
      Regional Lymph Nodes and Implications for Management.
AB  - The presence of cervical lymph node metastases is a major prognostic factor in
      squamous cell carcinoma of the head and neck. The presence of a solitary
      ipsilateral metastatic lymph node reduces expected survival by almost 50%, and
      the presence of regional metastatic nodes at the time of presentation is the
      strongest predictor of recurrence or the development of distant metastases or
      both. Therefore, accurate identification of metastatic cervical lymph nodes is
      essential for staging and treatment planning. Pretreatment imaging is important
      for identifying clinically occult pathologic nodes as well as delineating nodal
      size and morphologic characteristics used in staging. The role of imaging and its
      implications for management are reviewed, with emphasis on the traditional
      modalities and imaging criteria, including evaluation for extranodal extension.

PMID- 29031365
TI  - Chapter 3 The Role of PET/CT in Squamous Cell Carcinoma of the Head and Neck.
AB  - Head and neck squamous cell carcinoma is an important cause of cancer morbidity
      worldwide and has been stratified into human papillomavirus-related and human
      papillomavirus-unrelated subgroups that affect prognosis and now staging.
      Conventional anatomical imaging methods are suboptimal for the detection of
      regional and distant metastases that are important prognosticators associated
      with poor outcomes. Functional imaging with (F18)-fluorodeoxyglucose-positron
      emission tomography/computed tomography (PET/CT) is a useful tool in the
      management of head and neck squamous cell carcinoma, providing complementary
      physiological and anatomical information. In this article, optimal PET/CT
      technique will be reviewed and the pretreatment and posttreatment applications of
      PET/CT will be described. A simplified approach to imaging interpretation,
      including review of pearls and pitfalls will be discussed. An initial framework
      for follow-up evaluation will be provided.

PMID- 29031366
TI  - Chapter 4 Thyroid Malignancy: Staging and Restaging.
AB  - Determining the extent of disease is necessary for guiding the management of
      thyroid carcinomas. Diagnostic imaging, including ultrasound, computed
      tomography, magnetic resonance imaging, and nuclear medicine scans, plays an
      essential role in staging and restaging of thyroid carcinomas. This article
      reviews the approaches and imaging findings for evaluating the primary tumor,
      regional lymph node metastases, and distant metastases. In addition, potential
      pitfalls are discussed and depicted.

PMID- 29031367
TI  - Chapter 5 Ultrasound Characteristics of Benign vs Malignant Cervical Lymph Nodes.
AB  - With approximately 800 lymph nodes in the body, and more than one-third found
      within the head and neck, lymph nodes are a common site for neck pathology.
      Differentiation between benign and malignant lymph nodes is critical in accurate
      prognosis; similarly, treatment hinges on accurate identification of the etiology
      of the pathologic process. Key gray-scale and color Doppler ultrasound criteria
      can help accurately distinguish between benign and malignant lymph nodes.

PMID- 29031368
TI  - Chapter 6 Non-Squamous Cell Causes of Cervical Lymphadenopathy.
AB  - Cervical lymphadenopathy is a common indication for imaging evaluation of the
      neck. Besides metastatic squamous cell carcinoma of the head and neck, cervical
      lymphadenopathy can be due to many causes, with simple reactive lymphadenopathy
      on one end of the spectrum and malignant lymphadenopathy due to a distant
      infraclavicular primary, on the other end. A systematic approach to the cause of
      cervical lymphadenopathy, which includes pattern of lymph node enlargement, lymph
      node characteristics, systemic symptoms, and extranodal abnormalities, can be
      very useful in arriving at the correct diagnosis. In this article, various
      patterns of cervical lymphadenopathy due to non-squamous cell causes are
      discussed.

PMID- 29031369
TI  - Chapter 7 Image-Guided Fine-Needle Aspiration and Core Needle Biopsy of Neck
      Lymph Nodes: Techniques, Pearls, and Pitfalls.
AB  - Image-guided percutaneous biopsy of cervical lymph nodes is a minimally invasive
      method performed for the characterization of abnormal lymph nodes, staging, and
      for the detection of regional tumor recurrence. When performed with proper
      technique and by a skilled proceduralist, this technique offers a very high
      diagnostic yield and can potentially save the patient from more invasive
      procedures. Its diagnostic role in different disease processes and the variations
      in technique as well as its potential risks and pitfalls will be discussed in
      this article.

PMID- 29031370
TI  - Chapter 8 On the Horizon: Advanced Imaging Techniques to Improve Noninvasive
      Assessment of Cervical Lymph Nodes.
AB  - Conventional imaging modalities are limited in the evaluation of lymph nodes as
      they predominantly rely on size and morphology, which have suboptimal sensitivity
      and specificity for malignancy. In this review we will explore the role of "on
      the horizon" advanced imaging modalities that can look beyond the size and
      morphologic features of a cervical lymph node and explore its molecular nature
      and can aid in personalizing therapy rather than use the "one-size-fits-all"
      approach.

PMID- 29031372
TI  - We have come a long way, baby: "Explaining positive adaptation of immigrant youth
      across cultures".
AB  - Immigrant youth are and will continue to be a diverse and important part of
      Western nations. In this context, the study of immigrant youth adaptation has
      burgeoned. The papers of this special section represent a shift from a deficit
      based to a strength-based approach to immigrant youth. They focus on unpacking
      the immigrant paradox, often based on longitudinal, multilevel data. In this
      commentary, we discuss how the research findings and themes that emerge from
      these papers contribute to our understanding of the processes of development and
      acculturation, of the importance of individual differences and the role of
      context for immigrant youth adaptation. These studies show that we have come a
      long way ... but that we still have a long way to go.

PMID- 29031371
TI  - ASGE EndoVators Summit: Defining the role and value of endoscopic therapies in
      obesity management.

PMID- 29031373
TI  - ?

PMID- 29031374
TI  - [Prediabetes, definition and treatment].
AB  - Prediabetes corresponds to high levels of glycaemia on an empty stomach and/or
      lower tolerance to glucose. It is necessary to detect and treat it in order to
      prevent type 2 diabetes and its long-term morbidity-mortality. Several clinical
      trials, based notably on modifying the patient's lifestyle, have shown that
      prevention is possible. Bariatric surgery could constitute a favoured treatment
      option in prediabetic obese patients.

PMID- 29031375
TI  - ?

PMID- 29031376
TI  - [Jihadi radicalisation, legal definitions and reference points].
AB  - Since the terrorist threat has become part of daily life in France, two terms are
      systematically used in the public debate: radicalisation and deradicalisation. It
      is essential to understand exactly what these words encompass, and to know the
      legal framework associated with them, in order to limit all sorts of
      interpretations which serve to add to the confusion related to the current
      context.

PMID- 29031377
TI  - [Radicalisation and geopolitics, the pathways to violence].
AB  - Although the reasons for radicalisation appear diverse, the overwhelming majority
      of radicalised individuals and announcements claiming responsibility for
      terrorist attacks make reference to the same cause: western military
      interventions in Muslim countries. This raises the question of the link between
      radicalisation and geopolitics and the need to identify the motivations and the
      pathway between radicalisation and violent actions.

PMID- 29031378
TI  - [Terrorism, youth, ideals and paranoia].
AB  - Adolescence is a period of initiation during which individuals learn to free
      themselves from the hold of their impulses. Fanaticism prevents this process: the
      subject regresses into a paranoid-type sectarian and murderous way of
      functioning. The fanaticism of the adolescent could thereby be related to a
      distorted spiritual search for his or her purpose.

PMID- 29031379
TI  - [Mobilising caregivers to prevent radicalisation].
AB  - The policy for the prevention of radicalisation is based on the mobilisation of
      all government departments and territorial authorities as well as the
      coordination of social partners. In response to this challenge, health and social
      sector professionals have a key role to play both in detecting and managing
      people in the process of becoming radicalised.

PMID- 29031380
TI  - [Remaining a caregiver in the face of radicalised patients].
AB  - Caregivers care for patients of all cultural and religious origins. However, the
      current context of terrorist threat raises specific questions due to the
      government's appeals to help spot radicalised patients or those in the process of
      becoming so. These fundamental questions are related to professional secrecy and
      the ethics of care.

PMID- 29031381
TI  - [Adolescent vulnerabilities and radicalisation].
AB  - Radicalisation resonates with the psychological vulnerabilities of adolescents.
      The ups and downs encountered as they attempt to construct their identity and
      their need to dominate favour the destructive nature of young people lacking a
      sense of filiation and belonging. An adolescent's engagement corresponds to a
      search for limits, with an adherence to religious values and to a group to
      establish self-esteem. Subjectification, authorising the adolescent to separate
      themselves from their parents and their values through a period of crisis must be
      supported.

PMID- 29031382
TI  - [School in the face of radicalisation].
AB  - The school is a living space for children and adolescents. It is therefore the
      ideal place to spot worrying changes of attitude such as those which indicate
      radicalisation. It is also here that the fundamental knowledge and values of our
      French society are passed on. In this respect, schools have a key role to play in
      preventing what could lead young people to radical indoctrination.

PMID- 29031383
TI  - [Preventing radicalisation, the role of a Maison des adolescents].
AB  - Maisons des adolescents (Adolescent Centres) have a key role to play in the
      prevention of radicalisation. The Strasbourg centre uses a secondary prevention
      approach with an assessment of the potential danger of the adolescent's
      situation, orientation towards relevant professionals where necessary, and
      support which is both symptomatic and which targets the vulnerabilities of the
      individual and the family. Faced with this new adolescent symptom, the support,
      designed over the long term and ideally in partnership, must be able to adapt.

PMID- 29031384
TI  - [The mobile telephone as a tool for resisting sectarian ideas].
AB  - The 'Pocket films empathy' activity is aimed at young people at risk of dropping
      out of school and those in crisis, often struggling to interact and show empathy
      with others. It provides support led by street educators trained in the use of
      the mobile telephone as a tool for talking and creating. By inviting them to put
      images and words to their emotions and compare their points of view, it enables
      these young people to express their anger, to escape from the fascination for
      sectarian ideas and to start to create their own personal history as well as
      their history within their family and society as a whole.

PMID- 29031385
TI  - ?

PMID- 29031386
TI  - Impact of conjugated linoleic acid administered to rats prior and after
      carcinogenic agent on arachidonic and linoleic acid metabolites in serum and
      tumors.
AB  - The objective of the study was to assess the influence of conjugated linoleic
      acid (CLA) daily supplementation prior and after carcinogenic agent on the
      concentrations of eicosanoids - metabolites of arachidonic acid (15-, 12- or 5
      hydroxyeicosatetraenoic acids (15-, 12-, 5-HETE), prostaglandin E2 (PGE2)) and
      linoleic acid (13- or 9-hydroxyoctadecadienoic acids (13-, 9-HODE)) in rat serum
      and 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumors. Female rats were
      randomised into six groups, receiving 1% or 2% Bio-C.L.A or plant oil since the
      37th day of life throughout the whole experiment. Some rats (50-day-old) were
      administered DMBA to induce tumors. Eicosanoids were analyzed with LC-MS/MS. The
      study indicated that CLA supplemented daily to rats prior and after carcinogen
      administration affected concentrations of arachidonic and linoleic acid
      metabolites in rat serum and induced tumors. However, ratios of eicosanoids
      exerting opposite activities (e.g. 12-HETE/15-HETE) appear to act as more precise
      factors reflecting pathological changes in an organism than individual compounds.

PMID- 29031387
TI  - Metabolic pathways of oleic and palmitic acid are intensified in PCOS patients
      with normal androgen levels.
AB  - CONTEXT: The aetiology and pathogenesis polycystic ovary syndrome (PCOS) remain
      uncertain and thus the relative studies are still crucial. OBJECTIVE: Our aim was
      to analyse the fatty acids profiles of the main phospholipids species in serum
      from women with PCOS classified into phenotypes, and to diagnose women more
      susceptible to the occurrence of inflammatory state. DESIGN: PCOS screening tests
      were performed in The Clinic of Gynecology and Urogynecology of Pomeranian
      Medical University in the 2014-2015 years. SETTING: The study are designed for
      general community and a primary care or referral center. PATIENTS: 39 patients
      with PCOS, diagnosed according to Rotterdam's criteria, and 14 healthy women, as
      a control group, participated in this study. Fatty acid profiles were
      investigated using gas chromatography. A total of 36 fatty acids and their
      derivatives were identified and quantified. MAIN OUTCOME MEASURE: Changes in
      fatty acids profile in plasma from women with PCOS phenotypes are not identical.
      RESULTS: The analyses showed lowered level of total SFA, increase in the
      concentration of caprylic acid and the activation of palmitic and oleic acids
      pathways. The level of nervonic acid was several times higher than in the control
      group, and the levels of behenic and tricosanoic acids were reduced. CONCLUSIONS:
      In both phenotypes the alternative metabolic pathways of oleic acid were
      activated, but they were more pronounced in women with proper level of androgens.
      Gamma-linolenic acid (C18:3n6) can be a factor protecting hyperandrogenic women.

PMID- 29031388
TI  - Postnatal RBC arachidonic and docosahexaenoic acids deficiencies are associated
      with higher risk of neonatal morbidities and mortality in preterm infants.
AB  - Arachidonic (AA) and docosahexaenoic (DHA) acids are essential for the health and
      development of the neonate. Red blood cell (RBC) fatty acids were analyzed in 583
      very low birth weight (VLBW) infants and 274 term infants using capillary gas
      chromatography. VLBW infants exhibited significantly lower RBC AA (13.0 +/- 0.89
      vs. 13.5 +/- 0.98) and DHA (3.77 +/- 0.60 vs. 3.80 +/- 0.62), but higher n6:n3
      ratio (3.97 +/- 0.46 vs. 3.63 +/- 0.37) than term infants. In VLBW infants, DHA
      was lower in those born with small for gestational age (3.69 +/- 0.57 vs. 3.86 +/
      0.58) and those who suffered from neonatal sepsis (3.73 +/- 0.60 vs. 3.86 +/-
      0.55). Both AA and DHA were significantly lower in infants who developed
      respiratory distress syndrome or intraventricular hemorrhage, and those who died
      during the hospital stay. VLBW infants had lower postnatal RBC AA and DHA levels
      than term infants did. These deficits are associated with higher risk of neonatal
      morbidities and mortality.

PMID- 29031389
TI  - Maternal n-6 and n-3 fatty acid status during pregnancy is related to infant
      heart rate and heart rate variability: An exploratory study.
AB  - Early life heart rate (HR) and heart rate variability (HRV) reflect autonomic
      system maturation. Intervention with n-3 long chain polyunsaturated fatty acids
      (LCPUFAs) during pregnancy favorably affects fetal HR and HRV, complementing
      previous observations for n-3 LCPUFA intervention during infancy. The
      relationship between maternal fatty acid status during pregnancy and infant
      HR/HRV has not previously been assessed. The aim of this study was to explore
      associations between maternal n-6 and n-3 fatty acid status during pregnancy and
      infant HR and HRV at 2 weeks, 4 months, and 6 months of age using linear
      regression models. Maternal n-3 fatty acids were inversely related to infant HR
      and positively related to HRV. Conversely, maternal n-6 fatty acids were
      positively related to infant HR and inversely related to HRV. These data build on
      existing literature evidencing a role for n-3 fatty acids in accelerating
      autonomic development and link n-6 fatty acids to HR/HRV.

PMID- 29031390
TI  - Effects of postnatal omega-3 fatty acid supplementation on offspring pro
      resolving mediators of inflammation at 6 months and 5 years of age: A double
      blind, randomized controlled clinical trial.
AB  - BACKGROUND: Resolution of inflammation is an active process involving specialised
      pro-resolving mediators (SPMs) generated from the omega-3 fatty acids
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acid
      supplementation during infancy may provide an intervention strategy to modify
      SPMs and reduce oxidative stress. This study evaluates the effect of omega-3
      fatty acid supplementation in infancy on SPMs and F2-isoprostanes from 6 months
      to 5 years of age. METHODS: In a double-blind, placebo-controlled, parallel-group
      study design, 420 infants were randomized to a daily supplement of omega-3 fatty
      acids (280mg DHA and 110mg EPA) or olive oil (control), from birth to age 6
      months. Blood was collected at birth (cord blood), 6 months, 12 months and 5
      years. Plasma SPMs included 18-HEPE, E-series resolvins, 17-HDHA, D-series
      resolvins, 14-HDHA, 10S,17S-DiHDoHE, MaR1 and PD1. F2-isoprostanes were measured
      in plasma and urine, as markers of oxidative stress in vivo. RESULTS: The change
      in the concentration of 18-HEPE from birth to 6 months was greater in the omega-3
      fatty acid group (Ptimepoint*group=0.04) with levels at 6 months significantly
      higher than controls (P=0.02). Other SPMs were not different between the groups
      at any time point. Plasma 18-HEPE concentration were associated with erythrocyte
      EPA concentrations after age and group adjustments (P<0.001), but not with
      allergic outcomes at 12 months. There were no between-group differences in plasma
      and urinary F2-isoprostanes at any time point. CONCLUSION: Omega-3 fatty acid
      supplementation from birth to 6 months of age increased SPM at 6 months but the
      effects were not sustained after supplementation ceased. Given that 18-HEPE is a
      biologically active metabolite, future studies should examine how the increase in
      18-HEPE relates to potential health benefits of omega-3 fatty acid
      supplementation in infancy.

PMID- 29031391
TI  - A dose response study of the effect of prostaglandin E2 on thermal nociceptive
      sensitivity.
AB  - Inhibition of prostaglandin (PG) biosynthesis has been used to relieve pain for
      thousands of years. Today non-steroidal anti-inflammatory drugs (which largely
      inhibit PG synthesis) are widely used to treat pain. Four main types of PGs
      (PGD2, PGE2, PGF2 and PGI2) are synthesized from arachidonic acid during
      inflammation and have been demonstrated to impact nociception. PGE2 has been the
      most studied and utilized for its pain producing properties and has been
      demonstrated to increase hypersensitivity in rodent nociceptive behavioral models
      when applied centrally and/or peripherally. Surprisingly, there are no published
      reports that use withdrawal from radiant light beam (Hargreaves apparatus) to
      examine the dose response effect of peripherally applied PGE2 on thermal
      nociceptive hypersensitivity. To address this gap in the literature, we performed
      a dose response study examining the effect of PGE2 on thermal hypersensitivity
      (assessed using a Hargreaves apparatus) where rats were injected with 0.003-30MUg
      of PGE2, intradermally into the hindpaw. Thermal hypersensitivity was assessed by
      measuring withdraw latency from a radiant light beam (Hargreaves test) and our
      primary objective was to determine the dose of PGE2 causing the most pronounced
      increase in thermal hypersensitivity (i.e. lowest withdraw latency). A secondary
      objective was to determine the minimum dose of PGE2 required to cause
      statistically significant decreases in thermal withdrawal latency as compared to
      rats injected with vehicle. We found that rats injected with the 30MUg dose of
      PGE2 exhibited the most pronounced thermal nociceptive hypersensitivity though
      secondary analysis showed that rats injected with PGE2 doses of 0.03-30MUg had
      lower withdrawal latencies as compared to rats injected with vehicle. This work
      fills an evidence gap and provides context to guide dose selection in future
      rodent pain behavior studies.

PMID- 29031392
TI  - Effects of aspirin in combination with EPA and DHA on HDL-C cholesterol and ApoA1
      exchange in individuals with type 2 diabetes mellitus.
AB  - BACKGROUND/SYNOPSIS: Low-dose aspirin is an effective drug for the prevention of
      cardiovascular disease (CVD) events but individuals with diabetes mellitus can be
      subject to 'aspirin resistance'. Thus, aspirin's effect in these individuals is
      controversial. Higher blood levels of seafood-derived omega-3 polyunsaturated
      fatty acids (omega3) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
      also have beneficial effects in reducing risk of CVD events but few studies have
      examined the interaction of plasma EPA and DHA with aspirin ingestion.
      OBJECTIVE/PURPOSE: Our study examined the combinatory effects of EPA, DHA, and
      aspirin ingestion on HDL-cholesterol (HDL-C) and apoA-I exchange (shown to be
      associated with CVD event risk). METHODS: 30 adults with Type 2 diabetes mellitus
      ingested aspirin (81mg/day) for 7 consecutive days, EPA+DHA (2.6g/day) for 28
      days, then both for 7 days. Plasma was collected at baseline and at 5 subsequent
      visits including 4h after each aspirin ingestion. Mixed model methods were used
      to determine HDL-C-concentrations and apoA-I exchange compared to the baseline
      visit values. LOWESS curves were used for non-linear analyses of outcomes to help
      discern change patterns, which was followed by piecewise linear functions for
      formal testing of curvilinear relationships. RESULTS: Significant changes (p <
      0.05) compared to baseline in both HDL-C-concentrations and apoA-I exchange were
      present at different times. After 7 days of aspirin-only ingestion, apoA-I
      exchange was significantly modified by increasing levels of DHA concentration,
      with increased apoA-I exchange observed up until log(DHA) of 4.6 and decreased
      exchange thereafter (p = 0.03). These LOWESS curve effects were not observed for
      EPA or HDL-C (p > 0.05). Aspirin's effects on apoA-I exchange were the greatest
      when EPA or DHA concentrations were moderate compared to high or low. Comparison
      of EPA, DHA, and EPA+DHA LOWESS curves, demonstrated that the majority of the
      effect is due to DHA. CONCLUSION: Our results strongly suggest that plasma
      concentrations of EPA and DHA influence aspirin effects on lipid mediators of CVD
      event risk where their concentrations are most beneficial when moderate, not high
      or low. These effects on HDL-C cholesterol and apoA-I exchange are novel.
      Personalized dosing of DHA in those who take aspirin may be a beneficial option
      for patients with type 2 diabetes mellitus.

PMID- 29031393
TI  - Cytokine distribution in mothers and breastfed children after omega-3 LCPUFAs
      supplementation during the last trimester of pregnancy and the lactation period:
      A randomized, controlled trial.
AB  - OBJECTIVE: To determine whether maternal diet supplementation with omega-3 long
      chain polyunsaturated fatty acids (omega-3 LC-PUFAs) during the last trimester of
      pregnancy and the breastfeeding period influences the levels of inflammatory
      cytokines in mother and infants. MATERIAL AND METHOD: This registered, double
      blind randomized study included 46 pregnant women, who were randomly allocated to
      either an experimental group receiving 400mL/day of a fish oil-enriched dairy
      drink [320mg docosahexaenoic acid (DHA) + 72mg eicoapentaenoic acid] (FO group, n
      = 24) or to a control group receiving 400mL/day of a non-supplemented dairy drink
      (CT group, n = 22), from week 28 of pregnancy until the fourth month of
      lactation. During the study, maternal dietary patterns were monitored by a
      nutritionist, who encouraged compliance with current recommendations of fatty
      acids intake. DHA concentrations and cytokine levels (GM-CSF, IL-2, IL-4, IL-6,
      IL-10, INF-gamma and TNF-alpha) were measured in maternal plasma at the moment of
      recruitment and in maternal (n = 46) and infant (n = 46) plasma at birth and 2.5
      months after birth. RESULTS: Maternal plasmatic IL-4 levels were higher in FO
      than in CT subjects (p = 0.009). Additionally, a tendency was observed to higher
      IL-10 and IL-2 in the FO group. Plasmatic IL-6 however, was higher in CT mothers
      (p = 0.001). TNF-alpha was higher in CT infants at birth and 2.5 months after
      birth (p = 0.005). An analysis of possible relationships between DHA and the
      concentrations of different cytokines revealed negative correlation between
      maternal plasmatic IL-6 and DHA (higher plasmatic DHA corresponded to lower IL
      6). CONCLUSIONS: Maternal dietary omega-3 LC-PUFAs supplementation during
      critical periods like pregnancy, lactation and early newborn development may
      influence the levels of certain inflammatory cytokines, reducing pro-inflammatory
      cytokines and promoting an anti-inflammatory "environment".

PMID- 29031394
TI  - The role of cysteinyl leukotrienes and their receptors in refractory nasal
      polyps.
AB  - Leukotriene signaling is essential in many diseases, including asthma, allergic
      rhinitis, atherosclerosis and inflammatory bowel disease. Nevertheless, the
      expression of cysteinyl leukotrienes (CysLTs) and its receptors (CYSLTRs) in
      different types of nasal polyps (NPs), and the role of their antagonist in the
      treatment of refractory chronic rhinosinusitis with nasal polyps (CRSwNP) are not
      well understood. The following study investigates the expression of CysLTs and
      CYSLTRs in different types of NPs, as well as the role of leukotriene receptor
      antagonist (montelukast) in refractory NPs. Our data showed that CysLTs and
      CYSLTRs were significantly elevated in CRSwNP group (p < 0.05), particularly in
      IL-5+NP patients, compared to patients with chronic rhinosinusitis but without
      NPs (CRSsNP) and the control group. Furthermore, montelukast have shown the
      ability to inhibit the expression of MUC5AC, TSLP, IL-4, IL-5, IL-13, and TGF
      beta in NP explants after treatment with Staphylococcal Enterotoxins B (SEB). In
      addition, the patients treated by additional montelukast have better outcomes
      compared to those with INCS only. To conclude, our results demonstrate that the
      inhibition of CysLTs signaling by montelukast decreases the expression of
      cytokines and mucin in polyp explants, and in turn promotes the recovery in
      patients with refractory CRSwNP.

PMID- 29031395
TI  - Habitual dietary intake of fatty acids are associated with leptin gene expression
      in subcutaneous and visceral adipose tissue of patients without diabetes.
AB  - The purpose of the study was to investigate the association of leptin gene
      expression in visceral and subcutaneous adipose tissues with habitual fatty acid
      intake and its subtypes in adults. Visceral and subcutaneous adipose tissues were
      gathered from 97 participants aged >= 20, who had undergone elective abdominal
      surgery. Dietary fatty acid intakes including total fatty acids (TFA), saturated
      fatty acid (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids
      (PUFA), n-3, n-6, and n-9 fatty acids were collected using a valid and reliable
      food-frequency questionnaire (FFQ). The leptin gene expression in visceral and
      subcutaneous adipose tissues was measured by Real-Time PCR. After controlling for
      body mass index (BMI) and insulin, energy-adjusted dietary intake of SFA was
      positively and MUFA and n-3 fatty acids were negatively associated with
      subcutaneous and visceral adipose tissues leptin gene expression. Besides, a
      significant negative association of PUFA, n-6, and n-9 fatty acids with leptin
      mRNA from visceral adipose tissue were observed. In order to better
      interpretations of the results, the participants were allocated two groups
      including non-obese (BMI < 30kg/m2) and obese subjects (BMI >= 30kg/m2). Among
      non-obese participants, the SFA had positive and PUFA had negative association
      with leptin gene expression in both adipose tissues. Furthermore, in obese
      participants, n-3, n-6, and n-9 fatty acids had a negative association with
      visceral leptin gene expression. Habitual intake of SFA, MUFA, and n-3 fatty
      acids were associated with leptin gene expression in visceral and subcutaneous
      adipose tissues, suggesting an important role of quality and quantity of fatty
      acids intake in adipose tissue to regulate leptin expression.

PMID- 29031396
TI  - Supplementing dams with both arachidonic and docosahexaenoic acid has beneficial
      effects on growth and immune development.
AB  - Omega-3 long-chain polyunsaturated fatty acids (LCPUFAS) modulate immune cells in
      vitro and in vivo. This study investigated the effects of enriching the maternal
      diet with the n-6 and n-3 LCPUFAs, arachidonic (20:4n-6, 0.6%wt ARA) and
      docosahexaenoic acid (22:6n-3, 0.32%wt DHA), or 1:1 and 2:1 ratios (ARA: DHA) on
      total lipids in milk, total lipids, and immunophenotypes in plasma, lymph nodes,
      and spleen from isolated immune cells from 28d old pups. From day 15 of gestation
      to day 3 pp, Sprague-Dawley dams were fed a commercial chow. On day 3 pp litters
      were culled and pups (4 males and 2 females) randomly cross-fostered to dams who
      were randomized to one of the 5 experimental diets resulting in 20 male and 10
      female pups/diet group. Dams fed ARA or ARA: DHA had 28-36% more 20:4n-6 in milk
      and feeding DHA or ARA: DHA doubled 22:6n-3 in milk lipids (P<0.05). Feeding 1:1
      or 2:1 ARA: DHA resulted in greater pup weight at weaning (P<0.05). Compared to
      the control pups, ARA + DHA fed pups had a lower proportion of splenic CD45RA+
      lymphocytes. In summary, postpartum supplementation with a combination of ARA +
      DHA, compared to ARA or DHA alone, resulted in a higher content of ARA and DHA in
      dam's milk and tissues and had positive effects on growth, accompanied by
      evidence of progression toward a mature immune phenotype, and suggests a need for
      ARA when DHA is supplemented in the early diet. Additional investigations are
      needed of ARA immunomodulation to better understand and estimate nutritional
      requirements for LCPUFAs during early development.

PMID- 29031397
TI  - Modulation of the biomarkers of inflammation and oxidative stress by ruminant
      trans fatty acids and dairy proteins in vascular endothelial cells (HUVEC).
AB  - This study aimed to determine whether dairy macronutrients alter markers of
      inflammation and oxidative stress in endothelial cells. Human endothelial cells
      (HUVEC) were treated with ruminant trans fatty acids (rTFA), either trans
      vaccenic acid (tVA) or trans-palmitoleic acid (tPA), whey protein hydrolysate,
      leucine or combinations of rTFA and dairy protein compounds. Industrial TFA
      elaidic acid (EA) was also investigated and compared with rTFA. Inflammatory
      prostaglandins (PG) and F2-isoprostanes (F2-isoP) isomers, markers of oxidative
      stress, were assessed in cell supernatants by LC-MS/MS. Both tVA and tPA, as well
      as whey protein hydrolysate, decreased TNFalpha-induced PG excretion.
      Combinations of rTFA and dairy protein compounds decreased inflammation to a
      similar extent than rTFA alone. EA increased class VI F2-isoP isomers, whereas
      tVA mostly raised class III isomers. In summary, rTFA decreased inflammatory
      markers and increased oxidative stress markers in endothelial cells. Combinations
      of rTFA with whey proteins or leucine showed no additive effect.

PMID- 29031398
TI  - Polyunsaturated fatty acid levels at birth and child-to-adult growth: Results
      from the MEFAB cohort.
AB  - BACKGROUND: Prenatal exposure to polyunsaturated fatty acids (PUFAs) may
      influence childhood growth. However, available evidence mostly derived from short
      term studies is inconsistent. OBJECTIVE: To assess whether fetal PUFA exposure is
      associated with height and body mass index (BMI), a common measure of adiposity,
      from 6 months to 23 years of age. METHODS: In the MEFAB cohort, we assessed cord
      blood phospholipid n-3 and n-6 PUFA levels, reflecting fetal exposure in late
      pregnancy. For 250 (45.2% females) participants, we collected a total of 1770 (n=
      802 for females) repeated growth measurements from infancy to young adulthood. We
      examined sex-specific associations of PUFAs with height and BMI at different
      developmental ages (infant: 6 months; toddler: 2 years; pre-schooler: 4 years;
      school-aged child: 7 years; adolescent: 12 years; and young adult: 23 years)
      using fractional polynomial mixed models adjusted for important covariates.
      RESULTS: Higher n-3 PUFA levels were associated with higher infant length in
      males (beta= 0.44cm [95% CI: 0.07, 0.82] per SD increase), whereas, for females,
      higher n-6 PUFA concentrations were associated with lower length in infancy
      (beta= -0.69cm [95% CI: -1.08, -0.30] per SD increase). A higher ratio of n-3 to
      n-6 PUFAs was associated with higher infant length in both sexes (beta= 0.40cm
      [95% CI: 0.01, 0.78] and 0.42cm [95% CI: 0.05, 0.79] per unit increase for males
      and females, respectively). These associations were not detectable later in
      childhood and young adulthood. No associations with BMI were found at any time
      point examined. CONCLUSIONS: Our findings suggest a small sex-specific influence
      of PUFA status at birth on length in infancy, but this does not persist in later
      life up to young adulthood. PUFA status at birth does not seem to affect BMI from
      infancy till young adulthood.

PMID- 29031399
TI  - Ozone exposure effect on systemic prostaglandin F2alpha in rat plasma and urine
      may not reveal pulmonary damage through inflammation.
AB  - The acute ozone induced lung injury model has been widely used to explore injury
      and repair processes induced by oxidant overload. The current study evaluated
      acute ozone exposure effects on prostaglandin F2alpha (PGF2alpha) in male Fischer
      rat plasma and urine with the hypothesis that ozone may induce an inflammatory
      response in the body that can be measured by the induction of PGF2alpha. That
      might then lead to the identification of potential marker for acute lung injury
      through systemic inflammation. The time and dose-dependent effects of ozone
      exposure on the plasma and urinary levels of a major PGF2alpha metabolite15-keto
      dihydro-PGF2alpha were determined using a radioimmunoassay. No statistically
      significant differences in the PGF2alpha metabolite were found between the
      control and the experimental groups at either ozone exposure dose (2ppm and 5ppm)
      or any time point (2h, 7h and 16h) post exposure for plasma and at 7 different
      post exposure time points (between 2 and 80h) for urine. It is concluded that
      acute ozone exposure does not cause changes in plasma and urinary PGF2alpha, and
      therefore their measurement in plasma and urine may not be used to reveal
      pulmonary inflammation and damage by ozone.

PMID- 29031400
TI  - Neither linoleic acid nor arachidonic acid promote white adipose tissue
      inflammation in Fads2-/- mice fed low fat diets.
AB  - Dietary n-6 polyunsaturated fatty acids (PUFA) are widely perceived to promote
      inflammation and contribute to the development of chronic diseases. This dogma
      has been recently questioned due to evidence that n-6 PUFA, specifically linoleic
      acid (LA, 18:2n-6) and arachidonic acid (AA, 20:4n-6), do not appear to activate
      inflammatory signalling pathways when consumed in moderate amounts. However,
      delineating the independent roles of different dietary n-6 PUFA in vivo is
      challenging because LA is continuously converted into AA in a pathway regulated
      by the fatty acid desaturase 2 (Fads2) gene. The objective of this study was to
      investigate the independent roles of LA and AA on white adipose tissue (WAT)
      inflammatory signalling pathways using Fads2-/- mice. We hypothesized that
      dietary LA would not induce WAT inflammation, unless it was endogenously
      converted into AA. Male C57BL/6 wild-type (WT) and Fads2-/- mice were fed low-fat
      isocaloric diets containing either 7% corn oil w/w (CD, containing ~42% LA) or 7%
      ARASCO oil w/w (AD, containing ~27% AA) for 9 weeks. WAT inflammatory gene
      expression, protein levels, as well as phospholipid (PL) and triacylglycerol
      (TAG) fatty acid composition, were analyzed by RT-qPCR, western blots, and gas
      chromatography, respectively. Fads2-/- mice fed CD had high LA, but little-to-no
      GLA (18:3n-6), DGLA (20:3n-6), and AA in PLs and TAGs compared to their WT
      counterparts. In comparison, Fads2-/- and WT mice fed AD showed minimal
      differences in n-6 PUFA content in serum and WAT, despite having significantly
      more AA than CD-fed mice. No differences in gene expression for common
      inflammatory adipokines (e.g. Mcp-1, Ccl5, Tnfalpha) or key regulators of
      eicosanoid production (e.g. Cox-2, Alox-12, Alox-15) were detected in WAT between
      any of the diet and genotype groups. Furthermore, no differences in MCP-1, and
      total or phosphorylated STAT3 and p38 inflammatory proteins, were observed.
      Collectively, these results demonstrate that neither LA nor AA promote WAT
      inflammation when consumed as part of a low-fat diet. Therefore, the existing
      dogma surrounding n-6 PUFA and inflammation needs to be reconsidered.

PMID- 29031401
TI  - Screening of some lesser known tree-borne oilseed plants from North-East India
      for their oil content and major fatty acid components.
AB  - Forest of North-East India is rich in a variety of tree borne oilseeds and there
      were no serious efforts to exploit the less known oilseeds of the forest origin.
      Considering the vast plant wealth and with an objective to explore these untapped
      potentialities of oilseed resources of NE India, a research program was
      undertaken. The present communication is based on the investigation of seeds of
      14 lesser known plant species for fats and oils. The screened plant species
      exhibited oil yield ranging from 4.71% to 48.43% on dry weight basis. Alseodaphne
      andersonii showed significant amount of tocols while Garcinia xanthochymus showed
      significant amount of phytosterol. Gas liquid chromatography analysis of methyl
      ester extracted fatty acid indicated dominant fraction of Oleic acid in 6 numbers
      of species, followed by Linoleic acid in 3 species, Lauric acid in 3 species, and
      Palmitic acid in 2 species. The majority of the species (9 species) showed higher
      amount of unsaturated fatty acid content in the oils which suggested that the
      species may serve as valuable raw materials for vegetable oil which can be
      explored as substitute for industrial feasibility while restshowed higher amount
      of saturated fatty acids which suggested that these species may serve as
      important industrial by-products.

PMID- 29031402
TI  - Associations between maternal long-chain polyunsaturated fatty acid
      concentrations and child cognition at 7 years of age: The MEFAB birth cohort.
AB  - INTRODUCTION: Concentrations of the fish fatty acids EPA and DHA are low among
      Dutch women of reproductive age. As the human brain incorporates high
      concentrations of these fatty acids in utero, particularly during third trimester
      of gestation, these low EPA and DHA concentrations may have adverse consequences
      for fetal brain development and functioning. METHODS: Analyses were conducted
      using longitudinal observational data of 292 mother-child pairs participating in
      the MEFAB cohort. Maternal AA, DHA, and EPA were determined in plasma
      phospholipids - obtained in three trimesters - by gas-liquid chromatography.
      Cognitive function was assessed at 7 years of age, using the Kaufman Assessment
      Battery for Children, resulting in three main outcome parameters: sequential
      processing (short-term memory), simultaneous processing (problem-solving skills),
      and the mental processing composite score. Spline regression and linear
      regression analyses were used to analyse the data, while adjusting for potential
      relevant covariates. RESULTS: Only 2% of the children performed more than one SD
      below the mental processing composite norm score. Children with lower test scores
      (<25%) were more likely to have a younger mother with a higher pre-gestational
      BMI, less likely to be breastfed, and more likely to be born with a lower birth
      weight, compared to children with higher test scores (>=25%). Fully-adjusted
      linear regression models did not show associations of maternal AA, DHA, or EPA
      status during any of the pregnancy trimesters with childhood sequential and
      simultaneous processing. CONCLUSION: Maternal fatty acid status during pregnancy
      was not associated with cognitive performance in Dutch children at age 7.

PMID- 29031404
TI  - Machine learning methods and systems for data-driven discovery in biomedical
      informatics.

PMID- 29031403
TI  - The role of specialized pro-resolving mediators in maternal-fetal health.
AB  - Infants developing in a pro-inflammatory intrauterine environment have a
      significant risk for severe complications after birth. It has been shown that
      omega-3 fatty acids reduce inflammation, and also reduce early preterm births and
      decrease risk of infant admission to the neonatal intensive care unit. However,
      the mechanism for omega-3 fatty acids exerting these effects was previously
      unknown. Recent evidence has shown that downstream products of polyunsaturated
      fatty acids called specialized pro-resolving mediators may mediate inflammatory
      physiology, thus playing an important role in maternal-fetal health. In this
      review, current knowledge relating to specialized pro-resolving mediators in
      pregnancy, delivery, and perinatal disease states will be summarized.

PMID- 29031405
TI  - Life span-resolved nanotoxicology enables identification of age-associated
      neuromuscular vulnerabilities in the nematode Caenorhabditis elegans.
AB  - At present, the majority of investigations concerning nanotoxicology in the
      nematode C. elegans address short-term effects. While this approach allows for
      the identification of uptake pathways, exposition and acute toxicity,
      nanoparticle-organism interactions that manifest later in the adult life of C.
      elegans are missed. Here we show that a microhabitat composed of liquid S-medium
      and live bacteria in microtiter wells prolongs C. elegans longevity and is
      optimally suited to monitor chronic eNP-effects over the entire life span (about
      34 days) of the nematode. Silver (Ag) nanoparticles reduced C. elegans life span
      in concentrations >=10 MUg/mL, whereas nano ZnO and CeO2 (1-160 MUg/mL) had no
      effect on longevity. Monitoring of locomotion behaviors throughout the entire
      life span of C. elegans showed that Ag NPs accelerate the age-associated decline
      of swimming and increase of uncoordinated movements at concentrations of >=10
      MUg/mL, whereas neuromuscular defects did not occur in response to ZnO and CeO2
      NPs. By means of a fluorescing reporter worm expressing tryptophan hydroxylase
      1::DsRed Ag NP-induced behavioral defects were correlated to axonal protein
      aggregation and neurodegeneration in single serotonergic HSN as well as sensory
      ADF neurons. Notably, serotonergic ADF neurons represented a sensitive target for
      Ag NPs in comparison to GABAergic neurons that showed no signs of degeneration
      under the same conditions. We conclude that due to its analogy to the jellylike
      boom culture of C. elegans on microbe-rich rotting plant material liquid S-medium
      culture in spatially confined microtiter wells represents a relevant as well as
      practical tool for comparative identification of age-resolved nanoparticle
      effects and vulnerabilities in a significant target organism. Consistent with
      this, specifically middle-aged nematodes showed premature neuromuscular defects
      after Ag NP-exposure.

PMID- 29031406
TI  - Prevalence of antibiotic resistance genes from effluent of coastal aquaculture,
      South Korea.
AB  - The wide use of antibiotics in aquaculture for prophylactic and therapeutic
      purposes can potentially lead to the prevalence of antibiotic resistance genes
      (ARGs). This study reports for the first time the profile of ARGs from effluents
      of coastal aquaculture located in South Jeolla province and Jeju Island, South
      Korea. Using quantitative PCR (qPCR), twenty-two ARGs encoding tetracycline
      resistance (tetA, tetB, tetD, tetE, tetG, tetH, tetM, tetQ, tetX, tetZ, tetBP),
      sulfonamide resistance (sul1, sul2), quinolone resistance (qnrD, qnrS, aac(6')-Ib
      cr), beta-lactams resistance (blaTEM, blaCTX, blaSHV), macrolide resistance
      (ermC), florfenicol resistance (floR) and multidrug resistance (oqxA) and a class
      1 integrons-integrase gene (intI1) were quantified. In addition, Illumina Miseq
      sequencing was applied to investigate microbial community differences across fish
      farm effluents. Results from qPCR showed that the total number of detected ARGs
      ranged from 4.24 * 10-3 to 1.46 * 10-2 copies/16S rRNA gene. Among them, tetB and
      tetD were predominant, accounting for 74.8%-98.0% of the total ARGs. Furthermore,
      intI1 gene showed positive correlation with tetB, tetD, tetE, tetH, tetX, tetZ
      tetQ and sul1. Microbial community analysis revealed potential host bacteria for
      ARGs and intI1. Two genera, Vibrio and Marinomonas belonging to
      Gammaproteobacteria, showed significant correlation with tetB and tetD, the most
      dominant ARGs in all samples. Also, operational taxonomic units (OTUs)-based
      network analysis revealed that ten OTUs, classified into the phyla
      Proteobacteria, Cyanobacteria/Chloroplast, Bacteroidetes, Verrucomicrobia and an
      unclassified phylum, were potential hosts of tetracycline resistance genes (i.e.,
      tetA, tetG, tetH, tetM, tetQ and tetZ). Further systematic monitoring of ARGs is
      warranted for risk assessment and management of antibacterial resistance from
      fish farm effluents.

PMID- 29031407
TI  - Biomass burning particles in the Brazilian Amazon region: Mutagenic effects of
      nitro and oxy-PAHs and assessment of health risks.
AB  - Emissions from burning of biomass in the Amazon region have adverse effects on
      the environment and human health. Herein, particulate matter (PM) emitted from
      biomass burning in the Amazon region during two different periods, namely intense
      and moderate, was investigated. This study focused on: i) organic
      characterization of nitro- and oxy-polycyclic aromatic hydrocarbons (PAHs); ii)
      assessment of the excess lifetime cancer risk (LCR); and iii) assessment of the
      in vitro mutagenic effects of extractable organic matter (EOM). Further, we
      compared the sensitivity of two mutagenicity tests: Salmonella/microsome test and
      cytokinesis-block micronucleus (CBMN) with human lung cells. Among the nitro
      PAHs, 2-nitrofluoranthene, 7-nitrobenz[a]anthracene, 1-nitropyrene, and 3
      nitrofluoranthene showed the highest concentrations, while among oxy-PAHs, 2
      metylanthraquinone, benz[a]anthracene-7,12-dione, and 9,10-anthraquinone were the
      most abundant. The LCR calculated for nitro-PAH exposure during intense biomass
      burning period showed a major contribution of 6-nitrochrysene to human
      carcinogenic risk. The EOM from intense period was more mutagenic than that from
      moderate period for both TA98 and YG1041 Salmonella strains. The number of
      revertants for YG1041 was 5-50% higher than that for TA98, and the most intense
      responses were obtained in the absence of metabolic activation, suggesting that
      nitroaromatic compounds with direct-acting frameshift mutagenic activity are
      contributing to the DNA damage. Treatment of cells with non-cytotoxic doses of
      EOM resulted in an increase in micronuclei frequencies. The minimal effective
      dose showed that Salmonella/microsome test was considerably more sensitive in
      comparison with CBMN mainly for the intense burning period samples. This was the
      first study to assess the mutagenicity of EOM associated with PM collected in the
      Amazon region using Salmonella/microsome test. The presence of compounds with
      mutagenic effects, particularly nitro- and oxy-PAHs, and LCR values in the range
      of 10-5 indicate that the population is potentially exposed to an increased risk
      of DNA damage, mutation, and cancer.

PMID- 29031408
TI  - Acute kidney injury, when to dialyze critically ill patients?

PMID- 29031409
TI  - A Study of the Pharmacokinetic Properties and the In Vivo Kinetics of
      Erythrocytes Loaded With Dexamethasone Sodium Phosphate in Healthy Volunteers.
AB  - The objectives of this 2-phase study were to elucidate pharmacokinetics (PK), in
      vivo 24-hour recovery, and red blood cell (RBC) survival properties of RBC
      encapsulated dexamethasone sodium phosphate (DSP) prepared using the EryDex
      System (EDS). The 24-hour RBC recovery and T50 survival phase studied subjects
      were randomized to receive autologous RBCs loaded with either 15-20 mg DSP (Group
      1A) or sham saline (Group 2A). Loaded RBCs were radiolabeled with 51-Cr, and the
      labeled RBCs were followed over time in vivo. The PK phase evaluated dose levels
      of 2.5-5 mg (Group 1B) and 15-20 mg (Group 2B) DSP encapsulated in RBCs infused
      into healthy randomized subjects. The mean +/- SD 24-hour RBC recovery was 77.9%
      +/- 3.3% and 72.7% +/- 10.5% for Groups 1A and 2A, respectively. The mean +/- SD
      RBC life span was 84.3 +/- 8.3 days in Group 1A and 88.9 +/- 6.2 days in Group
      2A. The PK phase actual DSP loading doses (mean +/- SEM) were 4.2 +/- 0.27 mg and
      16.9 +/- 0.90 mg in Groups 1B and 2B, respectively. Release of dexamethasone from
      RBCs in vivo peaked at 1 hour, and a sustained release of dexamethasone could be
      detected until 35 days after the single intravenous infusion in Group 2B. The
      mean RBC in vivo recovery for DSP-loaded processed cells compares similarly to
      the 24-hour recovery of regulated RBC products intended for transfusion. There
      was a minimal but acceptable adverse impact on the survival of EDS-processed
      RBCs. DSP-loaded autologous RBCs, prepared using the EDS, delivered a sustained
      dose of dexamethasone in vivo.

PMID- 29031411
TI  - In Vivo Brain Glycine and Glutamate Concentrations in Patients With First-Episode
      Psychosis Measured by Echo Time-Averaged Proton Magnetic Resonance Spectroscopy
      at 4T.
AB  - BACKGROUND: Accumulating evidence suggests the involvement of abnormal
      glutamateric neurotransmission and N-methyl-D-aspartate receptor hypofunction in
      the pathophysiology of psychotic disorders. The purpose of this study was to
      quantify in vivo glutamate (Glu) and glycine (Gly) levels in patients with first
      episode psychosis as well as age-matched healthy control subjects with magnetic
      resonance spectroscopy (MRS). METHODS: The subjects were 46 patients with first
      episode psychosis (20 with a schizophrenia spectrum disorder, 26 with bipolar
      disorder) and 50 age-matched healthy control subjects. Glu and Gly levels were
      measured in vivo in the anterior cingulate cortex and posterior cingulate cortex
      of the subjects by using the echo time-averaged proton MRS technique at 4T (i.e.,
      modified point resolved spectroscopy sequence: 24 echo time steps with 20-ms
      increments). Metabolite levels were quantified using LCModel with simulated basis
      sets. RESULTS: Significantly higher Glu and Gly levels were found in both the
      anterior cingulate cortex and posterior cingulate cortex of patients with first
      episode psychosis as compared with healthy control subjects. Glu and Gly levels
      were positively correlated in patients. Patients with a schizophrenia spectrum
      disorder and bipolar disorder showed similar abnormalities. CONCLUSIONS: Our
      findings demonstrate abnormally elevated brain Glu and Gly levels in patients
      with first-episode psychosis by means of echo time-averaged proton MRS at 4T. The
      findings implicate dysfunction of N-methyl-D-aspartate receptor and glutamatergic
      neurotransmission in the pathophysiology of the acute early phase of psychotic
      illnesses.

PMID- 29031410
TI  - Harnessing Gut Microbes for Mental Health: Getting From Here to There.
AB  - There has been an explosion of interest in the study of microorganisms inhabiting
      the gastrointestinal tract (gut microbiota) and their impact on host health and
      physiology. Accumulating data suggest that altered communication between gut
      microbiota and host systems could participate in disorders such as obesity,
      diabetes mellitus, and autoimmune disorders as well as neuropsychiatric
      disorders, including autism, anxiety, and major depressive disorders. The
      conceptual development of the microbiome-gut-brain axis has facilitated
      understanding of the complex and bidirectional networks between gastrointestinal
      microbiota and their host, highlighting potential mechanisms through which this
      environment influences central nervous system physiology. Communication pathways
      between gut microbiota and the central nervous system could include autonomic,
      neuroendocrine, enteric, and immune systems, with pathology resulting in
      disruption to neurotransmitter balance, increases in chronic inflammation, or
      exacerbated hypothalamic-pituitary-adrenal axis activity. However, uncertainty
      remains regarding the generalizability of controlled animal studies to the more
      multifaceted pattern of human pathophysiology, especially with regard to the
      therapeutic potential for neuropsychiatric health. This narrative review
      summarizes current understanding of gut microbial influence over physiological
      function, with an emphasis on neurobehavioral and neurological impairment based
      on growing understanding of the gut-brain axis. Experimental and clinical data
      regarding means of therapeutic manipulation of gut microbiota as a novel
      treatment option for mental health are described, and important knowledge gaps
      are identified and discussed.

PMID- 29031413
TI  - Experiences in digitizing and digitally measuring a paper-based ECG archive.
AB  - BACKGROUND: No established method for digitizing and digital measuring of paper
      electrocardiograms (ECG) exists. We describe a paper ECG digitizing and digital
      measuring process, and report comparability to manual measurements. METHODS: A
      paper ECG was recorded from 7203 health survey participants in 1978-1980. With
      specific software, the ECGs were digitized (ECG Trace Tool), and measured
      digitally (EASE). A sub-sample of 100 ECGs was selected for manual measurements.
      RESULTS: The measurement methods showed good agreement. The mean global (EASE)
      (manual) differences were 1.4ms (95% CI 0.5-2.2) for PR interval, -1.0ms (95% CI 
      1.5-[-0.5]) for QRS duration, and 11.6ms (95% CI 10.5-12.7) for QT interval. The
      mean inter-method amplitude differences of RampV5, RampV6, SampV1, TampII and
      TampV5 ranged from -0.03mV to 0.01mV. CONCLUSIONS: The presented paper-to-digital
      conversion and digital measurement process is an accurate and reliable method,
      enabling efficient storing and analysis of paper ECGs.

PMID- 29031414
TI  - The application of ultrasound elastography in the shoulder.
AB  - Ultrasound elastography (EUS) is a recently developed method for the assessment
      of tissue elasticity by applying mechanical stress and subsequently analyzing
      tissue displacement with ultrasound. To date, mainly two different techniques are
      used in clinical practice: strain (compression) EUS and shear wave EUS. However,
      shear wave EUS has been shown to be more examiner independent and more reliable
      as this technique allows a quantitative measurement of tissue elasticity. There
      is increasing evidence that EUS can be used to evaluate mechanical properties of
      musculoskeletal tissue. Thus, it might be a powerful tool to detect and to
      monitor pathologic processes affecting the shoulder girdle. As ultrasound is an
      essential clinical tool for the examination of the shoulder, this review
      describes the two most important EUS techniques available for clinical use,
      presenting the published evidence on the applications of EUS for the evaluation
      of pathologic processes affecting the shoulder joint. In addition, technical
      issues, limitations, and future perspectives of these methods for the assessment
      of the shoulder are outlined.

PMID- 29031415
TI  - Usefulness of the CRT-SCORE for Shared Decision Making in Cardiac
      Resynchronization Therapy in Patients With a Left Ventricular Ejection Fraction
      of <=35.
AB  - Individualized estimation of prognosis after cardiac resynchronization therapy
      (CRT) remains challenging. Our aim was to develop a multiparametric prognostic
      risk score (CRT-SCORE) that could be used for patient-specific clinical shared
      decision making about CRT implantation. The CRT-SCORE was derived from an ongoing
      CRT registry, including 1,053 consecutive patients (age 67 +/- 10 years, 76%
      male). Using preimplantation variables, 100 multiple imputed datasets were
      generated for model calibration. Based on multivariate Cox regression models,
      cross-validated linear prognostic scores were calculated, as well as survival
      fractions at 1 and 5 years. Specifically, the CRT-SCORE was calculated using
      atrioventricular junction ablation, age, gender, etiology, New York Heart
      Association class, diabetes, hemoglobin level, renal function, left bundle branch
      block, QRS duration, atrial fibrillation, left ventricular systolic and diastolic
      functions, and mitral regurgitation, and showed a good discriminative ability
      (areas under the curve 0.773 at 1 year and 0.748 at 5 years). During the long
      term follow-up (median 60 months, interquartile range 31 to 85), all-cause
      mortality was observed in 494 (47%) patients. Based on the distribution of the
      CRT-SCORE, lower- and higher-risk patient groups were identified. Estimated mean
      survival rates of 98% at 1 year and 92% at 5 years were observed in the lowest 5%
      risk group (L5 CRT-SCORE: -4.42 to -1.60), whereas the highest 5% risk group (H5
      CRT-SCORE: 1.44 to 2.89) showed poor survival rates: 78% at 1 year and 22% at 5
      years. In conclusion, the CRT-SCORE allows accurate prediction of 1- and 5-year
      survival rates after CRT using readily available and CRT-specific clinical,
      electrocardiographic, and echocardiographic parameters. The model may assist
      clinicians in counseling patients and in decision making.

PMID- 29031416
TI  - Zinc silicate mineral-coated scaffold improved in vitro osteogenic
      differentiation of equine adipose-derived mesenchymal stem cells.
AB  - In current study we aimed to coat the PLLA scaffold with zinc (Zn) silicate
      mineral nanoparticles. Then, using equine adipose-derived stem cells (ASCs) we
      intended to compare the osteogenic induction potency of Zn silicate mineral
      coated PLLA scaffold with uncoated PLLA scaffold and tissue culture plastic
      (TCPS). Adipose tissues were collected from 3 horses, and isolation of ASCs was
      achieved by enzymatic digestion. PLLA scaffold was successfully prepared using a
      phase separation method and coated with Zn silicate mineral nanoparticles. The
      coating efficiency was then characterized by scanning electron microscopy and
      further evaluated with the application of fourier transform infrared microscopic
      imaging. Viability and growth characteristics of ASCs on TCPS, uncoated and
      coated PLAA scaffolds were investigated by MTT assay. Alizarin Red staining was
      performed for determination of calcium deposition following the osteogenic
      induction. Furthermore, other common osteogenic markers such as alkaline
      phosphatase (ALP) activity, calcium content, as well as osteogenic (Runx2, ALP,
      osteonectin, and collagen I) marker genes were also evaluated. Our data showed
      that Zn silicate mineral nanoparticles was coated successfully on PLLA scaffold
      and such scaffold had no detrimental effect on cell growth rate as indicated by
      MTT assay. Moreover, ASCs that differentiated on Zn silicate mineral-coated PLLA
      scaffold indicated higher ALP activity, more calcium content, and higher
      expression of bone-related genes than that on uncoated PLLA scaffold and TCPS.
      Adequate proliferation rate and higher expression of osteogenic markers of stem
      cells, provides this scaffold as a suitable substrate to support proliferation
      and differentiation of ASCs in equine.

PMID- 29031417
TI  - [Skin pigmentation induced by meropenem and levofloxacin].
AB  - BACKGROUND: Various cutaneous side-effects, including, exanthema, pruritus,
      urticaria and Lyell or Stevens-Johnson syndrome, have been reported with
      meropenem (carbapenem), a rarely-prescribed antibiotic. Levofloxacin
      (fluoroquinolone), a more frequently prescribed antibiotic, has similar cutaneous
      side-effects, as well as photosensitivity. We report a case of cutaneous
      hyperpigmentation induced by meropenem and levofloxacin. PATIENTS AND METHODS: A
      67-year-old male was treated with meropenem (1g*4 daily), levofloxacin (500mg
      twice daily) and amikacin (500mg daily) for 2 weeks, followed by meropenem,
      levofloxacin and rifampicin (600mg twice daily) for 4 weeks for osteitis of the
      fifth metatarsal. Three weeks after initiation of antibiotic therapy, dark
      hyperpigmentation appeared on the lower limbs, predominantly on the anterior
      aspects of the legs. Histology revealed dark, perivascular and interstitial
      deposits throughout the dermis, which stained with both Fontana-Masson and Perls
      stains. Infrared microspectroscopy revealed meropenem in the dermis of involved
      skin. After withdrawal of the antibiotics, the pigmentation subsided slowly.
      DISCUSSION: Similar cases of cutaneous hyperpigmentation have been reported after
      use of minocycline. In these cases, histological examination also showed iron
      and/or melanin deposits within the dermis, but the nature of the causative
      pigment remains unclear. In our case, infrared spectroscopy enabled us to
      identify meropenem in the dermis. Two cases of cutaneous hyperpigmentation have
      been reported following use of levofloxacin, and the results of histological
      examination were similar. This is the first case of cutaneous hyperpigmentation
      induced by meropenem.

PMID- 29031418
TI  - Demographic and socioeconomic predictors of treatment delays, pathologic stage,
      and survival among patients with penile cancer: A report from the National Cancer
      Database.
AB  - OBJECTIVES: To evaluate whether socioeconomic factors affect pathologic stage,
      treatment delays, pathologic upstaging, and overall survival (OS) in patients
      with penile cancer (PC). PATIENTS AND METHODS: A total of 13,283 eligible
      patients diagnosed with PC from 1998 to 2012 were identified from the National
      Cancer Database. Socioeconomic, demographic and pathologic variables were used in
      multivariable regression models to identify predictors of pathologic T stage >=2,
      pathologic lymph node positivity, cT to pT upstaging, treatment delays, and OS.
      RESULTS: A 5-year OS was 61.5% with a median follow-up of 41.7 months. Pathologic
      T stage >=2 was identified in 3,521 patients (27.2%), 1,173 (9.2%) had >=pN1 and
      388 (7.9%) experienced cT to pT upstaging. Variables associated with a higher
      likelihood of pathologic T stage >=2 included no insurance (OR = 1.79, P<0.001),
      lower higher education based on zip code (OR = 1.13, P = 0.027), black race (OR =
      1.17, P = 0.046) and Hispanic ethnicity (OR = 1.66, P<0.001). Patients with
      Hispanic ethnicity (OR = 1.46; P<0.001) or living in nonmetropolitan areas were
      more likely to have >=pN1 (P = 0.001). Lack of insurance was associated with cT
      to pT upstaging (OR = 2.05, P = 0.001) as was living in an urban vs. metropolitan
      area (OR = 1.35, P = 0.031). In addition to TNM stage, black vs. white race (HR =
      1.56, P<0.001), living in an urban vs. metropolitan area (hazard ratio [HR] =
      1.18, P = 0.022), age (HR = 1.04, P<0.001) and Charlson score (HR = 1.49,
      P<0.001) were associated with lower OS. CONCLUSION: Socioeconomic variables
      including no insurance, lower education, race, Hispanic ethnicity, and
      nonmetropolitan residence were found to be poor prognostic factors. Increased
      educational awareness of this rare disease may help reduce delays in diagnosis,
      improve prognosis and ultimately prevent deaths among socioeconomically
      disadvantaged men with PC.

PMID- 29031419
TI  - Impact of surgical waiting time on survival in patients with upper tract
      urothelial carcinoma: A national cancer database study.
AB  - PURPOSE: To evaluate the impact of surgical waiting time (SWT) on the survival
      outcome in patients with upper tract urothelial carcinoma (UTUC). MATERIALS AND
      METHODS: We identified patients with nonmetastatic UTUC who underwent radical
      nephroureterectomy (RNU) between 2004 and 2013 in the National Cancer Database.
      The association between SWT and overall survival (OS) was evaluated using Cox
      proportional hazards regression. SWT was categorized into 6 groups: SWT <= 7
      days, SWT 8 to 30 days, SWT 31 to 60 days, SWT 61 to 90 days, SWT 91 to 120 days,
      and SWT 121 to 180 days. Multivariable analyses were adjusted for patient, tumor,
      and facility-related factors. RESULTS: A total of 3,581 patients were included in
      the final overall cohort and 2,397 (66.9%) patients had the higher-risk disease
      (high-grade or >=pT2). Multivariable Cox regressions showed that patients in the
      groups of SWT 31 to 60 days, SWT 61 to 90 days, and SWT 91 to 120 days had
      similar OS compared with patients who had SWT of 8 to 30 days in the overall
      cohort and higher-risk cohort. Patients with SWT 121 to 180 days had worse OS (HR
      = 1.61, 95% CI: 1.19-2.19, P = 0.002 in the overall cohort; HR = 1.56, 95% CI:
      1.11-2.20, P = 0.010 in the higher-risk cohort). CONCLUSIONS: Increased SWT from
      diagnosis to RNU appears to be not associated with worse OS within 120 days after
      the diagnosis of UTUC but SWT>120 days may be associated with worsened survival.
      These findings might have important implications for trial design in the
      evaluation of neoadjuvant chemotherapy for UTUC and future clinical practice.

PMID- 29031420
TI  - Concordance between patient-reported and physician-reported sexual function after
      radical prostatectomy.
AB  - PURPOSE: Accurately tracking health-related quality-of-life after radical
      prostatectomy is critical to counseling patients and improving technique.
      Physicians consistently overestimate functional recovery. We measured concordance
      between surgeon-assessed and patient-reported outcomes and evaluated a novel
      method to provide feedback to surgeons. MATERIALS AND METHODS: Men treated with
      radical prostatectomy self-completed the International Index of Erectile Function
      6 questionnaire at each postoperative visit. Separately, physicians graded sexual
      function on a 5-point scale. International Index of Erectile Function -6 score<22
      and grade >=3 defined patient-reported and physician-assessed erectile
      dysfunction (ED), respectively. Feedback on concordance was given to physicians
      starting in May 2013 with the implementation of the Amplio feedback system. Chi
      square tests were used to assess agreement proportions and linear regression to
      evaluate changes in agreement after implementation. RESULTS: From 2009 to 2015,
      3,053 men completed at least 1 postprostatectomy questionnaire and had a
      concurrent independent physician-reported outcome. Prior to implementation of
      feedback in 2013, patients and physicians were consistent as to ED 83% of the
      time; in 10% of cases, physicians overestimated function; in 7% of cases,
      physicians, but not patients reported ED. Agreement increased after
      implementation of feedback but this was not statistically significant, likely
      owing to a ceiling effect. Supporting this hypothesis, increase in agreement
      postfeedback was greater during late follow-up (>=12mo), where baseline agreement
      was lower compared to earlier follow-up. CONCLUSIONS: Agreement was higher than
      expected at baseline; implementation of feedback regarding discrepancies between
      patient-reported and physician-assessed outcomes did not further improve
      agreement significantly. Our observed high rate of agreement may be partly
      attributed to our institutional practice of systematically capturing patient
      reported outcomes as part of normal clinical care.

PMID- 29031421
TI  - TLR2 activation induced by H. pylori LPS promotes the differential expression of
      claudin-4, -6, -7 and -9 via either STAT3 and ERK1/2 in AGS cells.
AB  - Gastric carcinogenesis has been associated to H. pylori virulence factors that
      induce a chronic inflammation process. Lipopolysaccharides play a role in chronic
      inflammatory responses via TLR2- and TLR4-dependent signaling pathways.
      Similarly, cellular invasiveness, metastatic potential and prognosis are usually
      associated to claudin-4, -6, -7 and -9 expression in gastric carcinogenesis.
      Therefore, the aim of this study was to determine if H. pylori LPS exerts an
      influence on carcinogenesis-related claudin expression and if it was directly
      regulated through the TLR2 pathway. Human antrum gastric adenocarcinoma AGS cells
      exposed or not to H. pylori LPS were used. Polyclonal anti-claudin-4, -6, -7 and 
      9, anti-TLR2, anti-pERK1/2 as well as rabbit monoclonal anti-pNFkappaB p65 and
      mouse monoclonal anti-CdX2 were used. ERK1/2 inhibitor UO126 and STAT3 inhibitor
      Stattic were also used. Western blot, immunofluorescence and confocal experiments
      were performed in whole cells as well as total protein, nuclear and cell membrane
      fractions. The results showed that H. pylori LPS increased the expression of TLR2
      in a time dependent bi-phasic manner (<12 and >12h exposure). Immunofluorescence
      using AGS monolayers corroborated the double phase TLR2 expression mainly on the
      cell membrane but a detectable signal was also determined in the cytoplasm of the
      cells. Activation of NFkB was downstream and depended on TLR2 expression as a
      statistically significant increase in pNFkB, that followed a pattern highly
      similar to the TLR2 expression was observed on the cell membrane fraction. The
      increase in TLR2 expression was accompanied by dramatically increased claudin-4
      expression in cultures exposed from 30m to 8h to LPS. Increased expression of
      claudin-6, -7 and -9 also increases in >12h LPS exposure times. The increase in
      claudins expression was also dependent on NFkB activation. The results also
      showed an increase in pSTAT3 that followed a bi-phasic pattern that began 30min
      after stimulation and was compatible with the increase in TLR2 expression. The
      expression of the claudin-4 related CDX2 transcription factor did not followed
      the biphasic pattern. The results also showed that claudin-4 expression was STAT3
      dependent whereas claudin-6, 7 and 9 expressions was ERK1/2 dependent. Our
      results suggest that H. pylori LPS induces TLR2 expression in the AGS cells, and
      that the longer the exposure to LPS, the greater the expression of TLR2 in the
      cell membrane. Consequently the expression of claudin-4, -6, -7 and -9 also
      increases.

PMID- 29031422
TI  - Modulation of alveolar macrophage innate response in proinflammatory-, pro
      oxidant-, and infection- models by mint extract and chemical constituents: Role
      of MAPKs.
AB  - There is a continuing need for discovering novel primary or adjunct therapeutic
      agents to treat inflammatory conditions and infections. Natural products have
      inspired the discovery of several modern therapeutics; however, there is a
      paucity of mechanistic information on their mode of action. This study
      investigated the therapeutic potential and mode of action of corn mint's (Mentha
      arvensis) leaf extract (ME) in alveolar macrophages (AMs) challenged with model
      pro-inflammatory (LPS), pro- oxidant (LPS or H2O2), and infection (Mycobacterium)
      agents and contribution of its dominant constituents rosmarinic acid, l-menthol,
      and l-menthone. LPS-induced inflammatory response in the murine AM cell line MH-S
      was significantly reduced in terms of pro-inflammatory cytokines (TNF-alpha, IL
      1alpha) and nitric oxide (NO) when pre- or post-treated with ME. The ME
      pretreatment of macrophages led to a significant increase (P<=0.05) in phagocytic
      activity toward Mycobacterium smegmatis and a greater pathogen clearance in 24h
      in both ME pre-treated (P<=0.05) and post-treated cells. Significant attenuation
      (P<=0.01) of reactive oxygen species (ROS) production in LPS- or H2O2-treated
      macrophages by pretreatment with whole mint extract (ME) was accounted for in
      part by the mint constituents rosmarinic acid and l-menthone. Attenuation of pro
      inflammatory response by ME pretreatment coincided with the significant reduction
      in total and phosphorylated JNK1/2, decrease in total p38, and increase in
      phospho-ERK1/2 thereby implying a role of differential modulation of MAPKs. Taken
      together, the results demonstrate that corn mint leaf components cause potent
      anti-inflammatory, anti-oxidant, and anti-infection effects in AMs via
      suppression of the production of cytokines/soluble mediators and ROS and
      increased pathogen clearance, respectively. To our knowledge, this is the first
      report on the mode of action of corn mint targeting the alveolar macrophages and
      on the potential role of MAPKs in immunomodulation by this product.

PMID- 29031423
TI  - The State of Surgical Axillary Management and Adjuvant Radiotherapy for Early
      stage Invasive Breast Cancer in the Modern Era.
AB  - BACKGROUND: For clinical T1-2N0 breast cancer, sentinel lymph node biopsy (SLNB)
      has been shown in American College of Surgeons Oncology Group (ACOSOG) Z0011 to
      be sufficient for women with 1 to 2 positive sentinel lymph nodes with no added
      benefit for completion axillary lymph node dissection (ALND). Z0011 specified
      whole breast radiotherapy (RT) using standard tangential fields; however, later
      analysis showed variation in field design. We assessed nationwide practice
      patterns and examined factors associated with patients undergoing completion ALND
      and subsequent radiation field design. PATIENTS AND METHODS: Women with clinical
      T1-2N0 breast cancer who underwent breast-conserving surgery, axillary staging,
      and whole breast RT in 2012 to 2013 were identified in the National Cancer
      Database. Multivariable logistic regression modeling was used to examine axillary
      management and RT, adjusting for demographic and clinicopathologic factors.
      RESULTS: Among 83,555 patients meeting criteria, 9.3% underwent upfront ALND,
      75.8% underwent SLNB only, and 14.9% underwent SLNB with completion ALND. From
      2012 to 2013, upfront SLNB increased from 90.1% to 91.4% (odds ratio, 1.14; P <
      .001). Among 9474 patients that underwent SLNB with 1 to 2 positive sentinel
      nodes, 31.2% received completion ALND. Among patients with 1 to 2 positive
      sentinel nodes, SLNB increased from 65.8% to 72.1% from 2012 to 2013 (P < .001).
      For patients with 1 to 2 positive lymph nodes that underwent SLNB only, 63.4%
      underwent breast RT, whereas 36.6% received breast and nodal RT. CONCLUSIONS:
      Nationwide practice patterns of axillary management vary. Despite an increasing
      rate of SLNB, many patients still receive upfront and completion ALND.
      Furthermore, there is significant variation in RT field design, and modern
      treatment guidelines are warranted for this patient population.

PMID- 29031424
TI  - The experience and influence of social support and social dynamics on
      cardiovascular disease prevention in migrant Pakistani communities: A qualitative
      synthesis.
AB  - OBJECTIVE: The objective of this research was to synthesise qualitative
      literature about the perceived influence and experience of social support, in
      relation to cardiovascular disease (CVD) prevention in migrant Pakistani
      communities. METHODS: Articles were systematically reviewed, critically
      appraised, and analysed using an adapted meta-ethnography approach. RESULTS:
      Sixteen qualitative studies on health behaviours related to CVD prevention were
      included. FINDINGS: include four sub-themes under two substantive thematic areas
      that focus on: 1) family dynamics and 2) community dynamics influenced by
      discrimination. For members of the Pakistani community, gendered family dynamics
      and discrimination from outside and within community networks influenced
      behaviour change. CONCLUSION: The authors of the synthesis developed multi
      layered, contextualised interpretations of the care needs of an established multi
      generational community. Future qualitative studies taking an intersectional
      approach to interpreting the role of social networks in migrant communities
      should take into account gender, identity, culture and faith. PRACTICE
      IMPLICATIONS: Health care providers should focus on cultural awareness and
      sensitivity during consultations. In particular, general practitioners can
      benefit from the insight they gain from patient experiences, allowing for more
      appropriate recommendations.

PMID- 29031425
TI  - Contents of Japanese pro- and anti-HPV vaccination websites: A text mining
      analysis.
AB  - OBJECTIVE: In Japan, the human papillomavirus (HPV) vaccination rate has sharply
      fallen to nearly 0% due to sensational media reports of adverse events. Online
      anti-HPV-vaccination activists often warn readers of the vaccine's dangers. Here,
      we aimed to examine frequently appearing contents on pro- and anti-HPV
      vaccination websites. METHODS: We conducted online searches via two major search
      engines (Google Japan and Yahoo! Japan). Targeted websites were classified as
      "pro," "anti," or "neutral" according to their claims, with the author(s)
      classified as "health professionals," "mass media," or "laypersons." We then
      conducted a text mining analysis. RESULTS: Of the 270 sites analyzed, 16 contents
      were identified. The most frequently appearing contents on pro websites were
      vaccine side effects, preventable effect of vaccination, and cause of cervical
      cancer. The most frequently appearing contents on anti websites were vaccine side
      effects, vaccine toxicity, and girls who suffer from vaccine side effects. Main
      disseminators of each content according to the author's expertise were also
      revealed. CONCLUSION: Pro-HPV vaccination websites should supplement deficient
      contents and respond to frequent contents on anti-HPV websites. PRACTICE
      IMPLICATIONS: Effective tactics are needed to better communicate susceptibility
      to cervical cancer, frequency of side effects, and responses to vaccine toxicity
      and conspiracy theories.

PMID- 29031426
TI  - Measuring ventricular repolarisation dynamics from ambulatory electrocardiography
      as non-invasive cardiac risk indices.

PMID- 29031427
TI  - [Penile prosthesis implantation: Indications and outcomes].
AB  - OBJECTIVE: Our aim was to present the indications and the outcomes of penile
      prosthesis implantation. METHODS: A literature review was performed through
      PubMed using the following keywords: penile implantation ; penile prosthesis;
      erectile dysfunction. RESULTS: Evolution of penile prosthesis devices led to get
      a fiable and effective treatment for men with erectile dysfunction who do not
      respond to less invasive therapy. Penile implant can also be useful in the
      treatment of Peyronie's disease, priapism and transgender surgery. Precise
      information related to this surgery, especially complications, permits to obtain
      high satisfaction scores. CONCLUSION: Penile implant is a reliable and safe
      solution for the management of erectile dysfunction resulting to high couple
      satisfaction ratings.

PMID- 29031428
TI  - Aortic valve replacement in small patients.
AB  - OBJECTIVES: Asians are smaller than Europeans and North Americans, but aortic
      valve replacement (AVR) in small patients has not been examined. We aimed to
      compare short- and mid-term outcomes of AVR between small and non-small patients.
      METHODS: We retrospectively divided 173 patients who underwent AVR into small (S,
      n = 95) and non-small (NS, n = 78) groups according to body surface area (<=1.6
      in men, <=1.5 in women) and analyzed differences in baseline characteristics,
      procedural and post-procedural variables, and survival. RESULTS: Mean age
      differed significantly between the S and NS groups (71.9 +/- 11.2 vs. 66.2 +/-
      9.8 years), as did the proportion of women (60.0% vs. 24.4%). Implanted valves
      (19.6 +/- 1.6 mm vs. 20.7 +/- 1.7 mm) were significantly smaller and more
      bioprosthetic valves (57.9% vs. 41.0%) were used in the S group. Effective
      orifice area index and the rate of moderate and severe patient-prosthesis
      mismatch were not significantly different. No significant intergroup differences
      were found in hospitalization duration, 30-day mortality, survival rates, or
      valve related complications. CONCLUSIONS: Small patients were older and the
      proportion of women was higher. The implanted aortic valves were smaller and more
      were biological prostheses. However, mortality rate did not differ and short- and
      mid-term outcomes were safe and favorable.

PMID- 29031429
TI  - Outbreak of group A Streptococcus emm94.0 affecting people who inject drugs in
      southwest England, April 2017.
AB  - We report an outbreak of invasive and noninvasive group A Streptococcus during
      April 2017 among people who inject drugs in southwest England. To date we have
      identified 14 cases linked to a specific town, all confirmed as group A
      Streptococcus emm94.0, a strain type not previously reported in the area. We have
      yet to identify a source for this ongoing outbreak. Actions described here may
      help reduce the burden of infection in vulnerable populations.

PMID- 29031430
TI  - Leadership line care rounds: Application of the engage, educate, execute, and
      evaluate improvement model for the prevention of central line-associated
      bloodstream infections in children with cancer.
AB  - To prevent central line-associated bloodstream infections (CLABSIs), leadership
      line care rounds (LLCRs) used the engage, educate, execute, and evaluate
      improvement model to audit compliance, identify barriers and opportunities,
      empower patients and families, and engage leadership. Findings of excellence and
      improvement opportunities were communicated to unit staff and managers. LLCRs
      contributed to compliance with CLABSI prevention interventions.

PMID- 29031431
TI  - Implementing an antibiotic stewardship program at a long-term acute care hospital
      in Detroit, Michigan.
AB  - BACKGROUND: The objective of the study was to assess health care providers'
      (HCPs) knowledge and attitude toward antimicrobial resistance (AMR) and implement
      an antimicrobial stewardship program (ASP) in a long-term acute care hospital
      (LTACH). METHODS: A questionnaire on antibiotic use and resistance was
      administered to HCP in an LTACH in Detroit, Michigan, between August 2011 and
      October 2011. Concurrently, a retrospective review of common antibiotic
      prescription practices and costs was conducted. Then, a tailored ASP was launched
      at the LTACH followed by 2-phase postimplementation assessment aiming at
      evaluating the impact of the ASP on antibiotic expenditure. RESULTS: Of all
      respondents (N = 26), 65% viewed AMR as a national problem, but only 38%
      perceived AMR as a problem at their facility. Most respondents were familiar with
      infections caused by resistant organisms such as methicillin-resistant
      Staphylococcus aureus, vancomycin-resistant enterococci, and extended-spectrum
      beta-lactamase; however, only 35% expressed confidence in treating infected
      patients. In the preimplementation phase, 15% of antimicrobial doses were
      inappropriate and 10 of 13 de-escalation opportunities were missed, resulting in
      additional $23,524.00 expenditure. In the first postimplementation phase, there
      was a 42% and 58% decrease in the use of daptomycin and tigecycline,
      respectively, resulting in $55,000 savings. In the second postintervention phase,
      total antimicrobial cost for treating a cohort of 28 patients in 2016 and 2017
      was $26,837.85 and $22,397.15, respectively. CONCLUSIONS: Introduction of an ASP
      in an LTACH improves antimicrobial prescribing practices, reduces cost, and is
      sustainable.

PMID- 29031432
TI  - Discontinuing contact precautions for multidrug-resistant organisms: A systematic
      literature review and meta-analysis.
AB  - BACKGROUND: Several single-center studies have suggested that eliminating contact
      precautions (CPs) for methicillin-resistant Staphylococcus aureus (MRSA) and
      vancomycin-resistant enterococci (VRE) control in nonoutbreak settings has no
      impact on infection rates. We performed a systematic literature review and meta
      analysis on the impact of discontinuing contact precautions in the acute care
      setting. METHODS: We searched PubMed, CINAHL, Cochrane Database of Systematic
      Reviews, Database of Abstracts of Reviews of Effects, and Embase through December
      2016 for studies evaluating discontinuation of contact precautions for multidrug
      resistant organisms. We used random-effect models to obtain pooled risk ratio
      estimates. Heterogeneity was evaluated with I2 estimation and the Cochran Q
      statistic. Pooled risk ratios for MRSA and VRE were assessed separately. RESULTS:
      Fourteen studies met inclusion criteria and were included in the final review.
      Six studies discontinued CPs for both MRSA and VRE, 3 for MRSA only, 2 for VRE
      only, 2 for extended-spectrum beta-lactamase-producing Escherichia coli, and 1
      for Clostridium difficile infection. When study results were pooled, there was a
      trend toward reduction of MRSA infection after discontinuing CPs (pooled risk
      ratio, 0.84; 95% confidence interval, 0.70-1.02; P = .07) and a statistically
      significant reduction in VRE infection (pooled risk ratio, 0.82; 95% confidence
      interval, 0.72-0.94; P = .005). CONCLUSIONS: Discontinuation of CPs for MRSA and
      VRE has not been associated with increased infection rates.

PMID- 29031433
TI  - Risk factors for health care-associated infection in hospitalized adults:
      Systematic review and meta-analysis.
AB  - BACKGROUND: Health care-associated infections (HAIs) are a public health problem
      that increase health care costs. This article aimed to systematically review the
      literature and meta-analyze studies investigating risk factors (RFs)
      independently associated with HAIs in hospitalized adults. METHODS: Electronic
      databases (MEDLINE, Embase, and LILACS) were searched to identify studies from
      2009-2016. Pooled risk ratios (RRs) or odds ratios (ORs) or mean differences
      (MDs) and 95% confidence intervals (CIs) were calculated and compared across the
      groups. This review followed the Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses statement. RESULTS: Of 867 studies, 65 met the criteria for
      review, and the data of 18 were summarized in the meta-analysis. The major RFs
      independently associated with HAIs were diabetes mellitus (RR, 1.76; 95% CI, 1.27
      2.44), immunosuppression (RR, 1.24; 95% CI, 1.04-1.47), body temperature (MD,
      0.62; 95% CI, 0.41-0.83), surgery time in minutes (MD, 34.53; 95% CI, 22.17
      46.89), reoperation (RR, 7.94; 95% CI, 5.49-11.48), cephalosporin exposure (RR,
      1.77; 95% CI, 1.30-2.42), days of exposure to central venous catheter (MD, 5.20;
      95% CI, 4.91-5.48), intensive care unit (ICU) admission (RR, 3.76; 95% CI, 1.79
      7.92), ICU stay in days (MD, 21.30; 95% CI, 19.81-22.79), and mechanical
      ventilation (OR, 12.95; 95% CI, 6.28-26.73). CONCLUSIONS: Identifying RFs that
      contribute to develop HAIs may support the implementation of strategies for their
      prevention, therefore maximizing patient safety.

PMID- 29031434
TI  - Validation of an electronic tool for flagging surgical site infections based on
      clinical practice patterns for triaging surveillance: Operational successes and
      barriers.
AB  - BACKGROUND: Surveillance is an effective strategy for reducing surgical site
      infections (SSIs); however, current identification methods are resource
      intensive. Therefore, we sought to validate an electronic SSI triaging tool for
      detection of probable infections and identify operational barriers and
      challenges. METHODS: A retrospective cohort study was conducted among all
      Veterans Affairs Surgical Quality Improvement Program (VASQIP)-reviewed surgeries
      at 2 Veterans Affairs medical centers from October 1, 2011-September 30, 2014.
      During the postoperative period, clinical and administrative variables associated
      with SSI (relevant microbiology order, antibiotic order, radiology order, and
      administrative codes) were extracted from the electronic medical record and used
      to score the probability (high, intermediate, and low) that an SSI occurred.
      VASQIP manual chart review was used as the gold standard of comparison. RESULTS:
      VASQIP manual review identified 118 SSIs out of 3,700 surgeries (3.2%). There
      were 2,041, 1,428, and 231 surgeries that met criteria for low, intermediate, and
      high probability for SSI. The tool's area under the curve was 0.86 (95%
      confidence interval, 0.82-0.89). The sensitivity among low-probability surgeries
      was 92.4%, and the specificity among high-probability surgeries was 95.1%.
      CONCLUSIONS: The electronic SSI tool has the potential to be used for triaging
      VASQIP surveillance toward the high-probability surgeries and to avoid manual
      review of surgeries with low probability of SSI.

PMID- 29031435
TI  - Description of a restriction program for gram-positive antimicrobial agents at an
      academic medical center.
AB  - This report examines the effectiveness of antimicrobial restriction at 1 tertiary
      care health care system by analyzing the consumption of restricted versus
      nonrestricted gram-positive agents over time for medical versus surgical units.
      Significant reductions in restricted antibiotic use were detected in 57% of
      medical units versus none of the surgical units. There were no significant
      reductions in nonrestricted antibiotic use. We think looking at antibiotic
      consumption by service line provides opportunities for targeted antibiotic
      restriction program refinement.

PMID- 29031436
TI  - Detection of concentric left ventricular wall hypertrophy by contrast-enhanced
      non-electrocardiogram-gated chest computed tomography.
AB  - BACKGROUND: No established measure of concentric left ventricular wall
      hypertrophy (cLVH) on routine computed tomography (CT) of the adult chest
      currently exists. The objective of this study was to identify and test linear
      measures for the detection of cLVH using transthoracic echocardiography (TTE) as
      the reference standard. METHODS: Contrast-enhanced non-electrocardiogram-gated
      chest CTs acquired within two weeks of TTE were retrospectively evaluated. Two
      radiologists independently made trans-axial measurements in the proximal half of
      the left ventricle at its approximate widest internal diameter: maximum septal
      thickness (sept), maximum lateral wall thickness (lat), and inner (Id) and outer
      (Od) wall-wall diameters at the level of greatest combined myocardial thickness.
      The sum of sept and lat, hereafter Thmax, and modified cross-sectional area (Amod
      = Od2 - Id2) were calculated. Sept, lat, Thmax, and Amod were evaluated by
      receiver operating characteristic (ROC) curves using TTE as the reference
      standard. Thresholds were optimized for specificity and applied to a validation
      cohort. Inter-rater agreement was assessed by a simple unweighted Kappa statistic
      (kappa). RESULTS: Sept and Amod were selected based on areas under the ROC curves
      of 0.75 and 0.71, respectively, using 100 CTs. Thresholds of 1.6 cm and 30 cm2,
      respectively, showed similar specificities of 98% with sensitivities of 27% and
      30%, respectively. Applied to a validation cohort of 100 CTs, sept had higher
      combined positive predictive value (75%), inter-rater agreement (kappa = 0.58),
      specificity (91%), and sensitivity (24%). CONCLUSION: Linear measures demonstrate
      utility in the diagnosis of cLVH on routine contrast-enhanced chest CT.

PMID- 29031438
TI  - Photocatalysis: Preface.

PMID- 29031437
TI  - Incidental CT finding of myocardial calcifications following severe septic shock.

PMID- 29031439
TI  - Photoelectrocatalytic reduction of CO2 to methanol over a photosystem II-enhanced
      Cu foam/Si-nanowire system.
AB  - A solar-light double illumination photoelectrocatalytic cell (SLDIPEC) was
      fabricated for autonomous CO2 reduction and O2 evolution with the aid of
      photosystem II (PS-II, an efficient light-driven water-oxidized enzyme from
      nature) and utilized in a photoanode solution. The proposed SLPEC system was
      composed of Cu foam as the photoanode and p-Si nanowires (Si-NW) as the
      photocathode. Under solar irradiation, it exhibited a super-photoelectrocatalytic
      performance for CO2 conversion to methanol, with a high evolution rate
      (41.94mmol/hr), owing to fast electron transfer from PS-II to Cu foam. Electrons
      were subsequently trapped by Si-NW through an external circuit via bias voltage
      (0.5V), and a suitable conduction band potential of Si (-0.6eV) allowed CO2 to be
      easily reduced to CH3OH at the photocathode. The constructed Z-scheme between Cu
      foam and Si-NW can allow the SLDIPEC system to reduce CO2 (8.03mmol/hr) in the
      absence of bias voltage. This approach makes full use of the energy band mismatch
      of the photoanode and photocathode to design a highly efficient device for
      solving environmental issues and producing clean energy.

PMID- 29031440
TI  - Removal of antibiotics in a parallel-plate thin-film-photocatalytic reactor:
      Process modeling and evolution of transformation by-products and toxicity.
AB  - Photocatalytic degradation of sulfamethoxazole (SMX) antibiotic has been studied
      under recycling batch and homogeneous flow conditions in a thin-film coated
      immobilized system namely parallel-plate (PPL) reactor. Experimentally designed,
      statistically evaluated with a factorial design (FD) approach with intent to
      provide a mathematical model takes into account the parameters influencing
      process performance. Initial antibiotic concentration, UV energy level,
      irradiated surface area, water matrix (ultrapure and secondary treated
      wastewater) and time, were defined as model parameters. A full of 25 experimental
      design was consisted of 32 random experiments. PPL reactor test experiments were
      carried out in order to set boundary levels for hydraulic, volumetric and defined
      defined process parameters. TTIP based thin-film with polyethylene glycol+TiO2
      additives were fabricated according to pre-described methodology. Antibiotic
      degradation was monitored by High Performance Liquid Chromatography analysis
      while the degradation products were specified by LC-TOF-MS analysis. Acute
      toxicity of untreated and treated SMX solutions was tested by standard Daphnia
      magna method. Based on the obtained mathematical model, the response of the
      immobilized PC system is described with a polynomial equation. The statistically
      significant positive effects are initial SMX concentration, process time and the
      combined effect of both, while combined effect of water matrix and irradiated
      surface area displays an adverse effect on the rate of antibiotic degradation by
      photocatalytic oxidation. Process efficiency and the validity of the acquired
      mathematical model was also verified for levofloxacin and cefaclor antibiotics.
      Immobilized PC degradation in PPL reactor configuration was found capable of
      providing reduced effluent toxicity by simultaneous degradation of SMX parent
      compound and TBPs.

PMID- 29031441
TI  - Preparation of Ti species coating hydrotalcite by chemical vapor deposition for
      photodegradation of azo dye.
AB  - TiO2 in anatase crystal phase is a very effective catalyst in the photocatalytic
      oxidation of organic compounds in water. To improve its photocatalytic activity,
      the Ti-coating MgAl hydrotalcite (Ti-MgAl-LDH) was prepared by chemical vapor
      deposition (CVD) method. Response surface method (RSM) was employed to evaluate
      the effect of Ti species coating parameters on the photocatalytic activity, which
      was found to be affected by the furnace temperature, N2 flow rate and influx time
      of precursor gas. Application of RSM successfully increased the photocatalytic
      efficiency of the Ti-MgAl-LDH in methylene blue photodegradation under UV
      irradiation, leading to improved economy of the process. According to the results
      from X-ray diffraction, scanning electron microscopy, Brunner-Emmet-Teller and
      Barrett-Joyner-Hallender, thermogravimetric and differential thermal analysis, UV
      vis diffuse reflectance spectra analyses, the Ti species (TiO2 or/and Ti4+) were
      successfully coated on the MgAl-LDH matrix. The Ti species on the surface of the
      Ti-MgAl-LDH lead to a higher photocatalytic performance than commercial TiO2-P25.
      The results suggested that CVD method provided a new approach for the industrial
      preparation of Ti-coating MgAl-LDH material with good photocatalytic
      performances.

PMID- 29031442
TI  - Preparation and photocatalytic properties of porous C and N co-doped TiO2
      deposited on brick by a fast, one-step microwave irradiation method.
AB  - A one-step microwave irradiation method was used to deposit carbon and nitrogen
      co-doped TiO2 ((C, N)-TiO2) on commercial brick ((C, N)-TiO2/brick). The as
      prepared samples were characterized by X-ray diffraction, ultraviolet-visible (UV
      vis) diffuse reflectance spectroscopy, photoluminescence spectroscopy, X-ray
      photoelectron spectroscopy, and scanning electron microscopy (SEM). A selective
      technique was also used to investigate the concentration of hydroxyl radicals
      during UV-vis irradiation of the Methyl Orange solution with the as-prepared
      samples. The C and N dopants enhanced visible light absorption and provided a
      longer lifetime for the photo-generated electron-hole pairs. The SEM images
      showed that the as-prepared sample is porous. The dark adsorption and
      photodegradation test for (C, N)-TiO2/brick showed good photodegradation and good
      recyclability. The best photodegradation rate was 94% after 2hr. The maximum
      degradation rate was maintained even after the 6th cycle. The good photocatalytic
      properties are attributed to the enhanced visible light absorption, enhanced
      pollutant adsorption arising from the porous structure of the (C, N)-TiO2 thin
      film, and longer lifetime of the photo-generated electron-hole pairs. (C, N)
      TiO2/brick should have potential commercial applications in photodegradation
      processes because of its low cost, good photodegradation, and excellent
      recyclability.

PMID- 29031443
TI  - TiO2-PANI/Cork composite: A new floating photocatalyst for the treatment of
      organic pollutants under sunlight irradiation.
AB  - A novel photocatalyst based on TiO2-PANI composite supported on small pieces of
      cork has been reported. It was prepared by simple impregnation method of the
      polyaniline (PANI)-modified TiO2 on cork. The TiO2-PANI/Cork catalyst shows the
      unique feature of floating on the water surface. The as-synthesized catalyst was
      characterized by X-ray diffraction (XRD), scanning electron micrograph (SEM),
      transmission electron microscopy (TEM), thermogravimetric analysis (TGA), Fourier
      transform infrared spectroscopy (FT-IR), UV-vis diffuse reflectance spectra (UV
      vis DRS) and the Brunauer-Emmett-Teller (BET) surface area analysis.
      Characterization suggested the formation of anatase highly dispersed on the cork
      surface. The prepared floating photocatalyst showed high efficiency for the
      degradation of methyl orange dye and other organic pollutants under solar
      irradiation and constrained conditions, i.e., no-stirring and no-oxygenation. The
      TiO2-PANI/Cork floating photocatalyst can be reused for at least four consecutive
      times without significant decrease of the degradation efficiency.

PMID- 29031444
TI  - In-situ synthesis of TiO2 rutile/anatase heterostructure by DC magnetron
      sputtering at room temperature and thickness effect of outermost rutile layer on
      photocatalysis.
AB  - TiO2 rutile/anatase heterostructure thin films with varying rutile thickness have
      been in-situ synthesized via DC magnetron sputtering with Ar gas at room
      temperature. The crystal texture, surface morphology, energy gap and optical
      properties of the films have been investigated by X-ray diffraction meter,
      grazing incidence X-ray diffraction meter, Raman spectroscopy, scanning electron
      microscopy, and UV-visible spectrophotometer, which indicates that the
      rutile/anatase heterostructure films are successfully fabricated. The further
      degradation experiments display that the photocatalytic activity can be
      dramatically affected by the thickness of the outmost rutile layer and the 100nm
      thickness exhibits the best performance in all of the TiO2 thin films. With the
      increase of the outmost rutile layer, the optical band gap of TiO2 film displays
      a systematic decrease slightly. However, the change in photocatalytic activity
      does not coincide with that in the band gap. The photoresponse and
      electrochemical properties of the thin films have been characterized to
      understand the mechanism of the varied photocatalytic activity.

PMID- 29031445
TI  - Preparation of Ag@AgCl-doped TiO2/sepiolite and its photocatalytic mechanism
      under visible light.
AB  - A cube-like Ag@AgCl-doped TiO2/sepiolite (denoted Ag@AgCl-TiO2/sepiolite) was
      successfully synthesized via a novel method. X-ray diffraction, scanning electron
      microscopy, energy dispersion X-ray fluorescence, X-ray photoelectron
      spectroscopy, Fourier transform infrared spectroscopy, and diffuse reflectance
      ultraviolet-visible spectroscopy were performed to determine the structure and
      physicochemical properties of Ag@AgCl-TiO2/sepiolite. SEM micrographs revealed
      that Ag@AgCl nanoparticles and TiO2 film are well deposited on the surface of
      tube-like sepiolite. As a result, Ag@AgCl-TiO2/sepiolite exhibits a red shift
      relative to TiO2/sepiolite. Photocatalytic experiments demonstrated that the
      dosage of catalysts plays an important role during photocatalysis. The
      photoelectrochemical activities of Ag@AgCl-TiO2/sepiolite and TiO2/sepiolite were
      also investigated. Photocurrent responses confirmed that the ability of Ag@AgCl
      TiO2/sepiolite to separate photo-generated electron-hole pairs is stronger than
      that of TiO2/sepiolite. Methylene Blue degradation is also improved under
      alkaline conditions and visible light irradiation because more OH is produced by
      visible light excitation. This excellent catalytic ability is mainly attributed
      to the formed Ag nanoparticles and the Schottky barrier at the Ag/TiO2 interface.
      Active species analysis indicated that O2- and h+ are implicated as active
      species in photocatalysis. Therefore, catalysts are excited to produce abundant
      electron-hole pairs after they absorb photons in photocatalysis.

PMID- 29031446
TI  - Pd-MnO2 nanoparticles/TiO2 nanotube arrays (NTAs) photo-electrodes photo
      catalytic properties and their ability of degrading Rhodamine B under visible
      light.
AB  - Pd-MnO2/TiO2 nanotube arrays (NTAs) photo-electrodes were successfully fabricated
      via anodization and electro deposition subsequently; the obtained Pd-MnO2/TiO2
      NTAs photo electrodes were analyzed by scanning electron microscopy (SEM), X-ray
      diffraction (XRD) and characterized accordingly. Moreover, the light harvesting
      and absorption properties were investigated via ultraviolet-visible diffuse
      reflectance spectrum (DRS); photo degradation efficiency was investigated via
      analyzing the photo catalytic degradation of Rhodamine B under visible
      illumination (xenon light). The performed analyses illustrated that Pd-MnO2
      codoped particles were successfully deposited onto the surface of the TiO2
      nanotube arrays; DRS results showed significant improvement in visible light
      absorption which was between 400 and 700nm. Finally, the photo catalytic
      degradation efficiency results of the designated organic pollutant (Rhodamine B)
      illustrated a superior photocatalytic (PC) efficiency of approximately 95%
      compared to the bare TiO2 NTAs, which only exhibited a photo catalytic
      degradation efficiency of approximately 61%, thus it indicated the significant
      enhancement of the light absorption properties of fabricated photo electrodes and
      their yield of OH radicals.

PMID- 29031447
TI  - Highly efficient Zr doped-TiO2/glass fiber photocatalyst and its performance in
      formaldehyde removal under visible light.
AB  - Zr-doped-TiO2 loaded glass fiber (ZT/GF) composite photocatalysts with different
      Zr/Ti ratios were prepared with a sol-gel process. Zr4+ can replace Ti4+ in the
      TiO2 lattice, which is conducive to forming the anatase phase and reducing the
      calcination temperature. The glass fiber carrier was responsible for better
      dispersion and loading of Zr-doped-TiO2 particles, improving the applicability of
      the Zr-doped-TiO2. The ZT/GF photocatalysts were characterized by X-ray
      diffraction (XRD), scanning electron microscope (SEM), Fourier transform infrared
      spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-vis) and Barrett
      Joyner-Halenda (BJH). The performance of photocatalysts with different loading
      was evaluated in formaldehyde degradation under visible light at room
      temperature. ZT/GF0.2 exhibited the highest activity, with a formaldehyde removal
      rate as high as 95.14% being observed, which is better than that of the
      photocatalyst particles alone. The stability of the catalyst was also tested, and
      ZT/GF exhibited excellent catalytic performance with 94.38% removal efficiency,
      even after seven uses.

PMID- 29031448
TI  - La/Ce-codoped Bi2O3 composite photocatalysts with high photocatalytic performance
      in removal of high concentration dye.
AB  - A series of La/Ce-codoped Bi2O3 composite photocatalysts were fabricated via
      hydrothermal-calcination process. The as-prepared products were intensively
      characterized by some physicochemical characterizations like N2 physical
      adsorption, X-ray powder diffraction (XRD), scanning electron microscope (SEM),
      transmission electron microscope (TEM), UV-Vis diffuse reflectance (UV-Vis DRS),
      Fourier transform infrared spectroscopy (FT-IR), photoelectrochemical
      measurements, and photoluminescence (PL) spectroscopy. The characterization
      results indicated that La and Ce doping induced obvious crystal phase
      transformation in Bi2O3, from monoclinic to tetragonal phase. La and Ce codoping
      also gave rise to the obvious synergetic effects, e.g., the lattice contraction
      of Bi2O3, the decrease of crystal size and the increase of surface area. The
      photocatalytic performance of the prepared catalysts was evaluated by removal of
      dye acid orange II with high concentration under visible light irradiation.
      Results showed that La/Ce-codoped Bi2O3 displayed much higher photocatalytic
      performance than that of bare Bi2O3, single La or Ce doped Bi2O3 samples. The
      superior photocatalytic activity was mainly attributed to the improved texture
      and surface properties and the synergistic effects of La and Ce codoping on
      suppressing the recombination of photo-generated electrons (e-) and holes (h+).

PMID- 29031449
TI  - Enhancement of photocatalytic efficiency by in situ fabrication of BiOBr/BiVO4
      surface junctions.
AB  - Surface junctions between BiOBr and BiVO4 were synthesized. The BiOBr/BiVO4 with
      1wt.% of BiOBr exhibited the highest photocatalytic activity in the degradation
      of RhB under visible-light irradiation. It was found that the highly efficient
      adsorption of RhB molecules via the electrostatic attraction between Br- and
      cationic N(Et)2 group played a key role for the high photocatalytic activities of
      BiOBr/BiVO4. This efficient adsorption promoted the N-deethylation of RhB and
      thus accelerated the photocatalytic degradation of RhB. Moreover, the metal-to
      metal charge transfer (MMCT) mechanism was proposed, which revealed the concrete
      path paved with Bi-O-Bi chains for the carrier migration in BiOBr/BiVO4. The
      interaction between photoexcited RhB* and the Bi3+ in BiVO4 provided the driving
      force for the migration of photo-generated carriers along the Bi-O-Bi chains.
      This work has not only demonstrated the important role of efficient adsorption in
      the photocatalytic degradation of organic contaminants, but also developed a
      facile strategy to improve the efficiency of photocatalysts.

PMID- 29031450
TI  - Selective oxidation of benzyl alcohols to benzoic acid catalyzed by eco-friendly
      cobalt thioporphyrazine catalyst supported on silica-coated magnetic nanospheres.
AB  - A novel magnetically recoverable thioporphyrazine catalyst (CoPz(S
      Bu)8/SiO2@Fe3O4) was prepared by immobilization of the cobalt octkis(butylthio)
      porphyrazine complex (CoPz(S-Bu)8) on silica-coated magnetic nanospheres
      (SiO2@Fe3O4). The composite CoPz(S-Bu)8/SiO2@Fe3O4 appeared to be an active
      catalyst in the oxidation of benzyl alcohol in aqueous solution using hydrogen
      peroxide (H2O2) as oxidant under Xe-lamp irradiation, with 36.4% conversion of
      benzyl alcohol, about 99% selectivity for benzoic acid and turnover number (TON)
      of 61.7 at ambient temperature. The biomimetic catalyst CoPz(S-Bu)8 was supported
      on the magnetic carrier SiO2@Fe3O4 so as to suspend it in aqueous solution to
      react with substrates, utilizing its lipophilicity. Meanwhile the CoPz(S-Bu)8 can
      use its unique advantages to control the selectivity of photocatalytic oxidation
      without the substrate being subjected to deep oxidation. The influence of various
      reaction parameters on the conversion rate of benzyl alcohol and selectivity of
      benzoic acid was investigated in detail. Moreover, photocatalytic oxidation of
      substituted benzyl alcohols was obtained with high conversion and excellent
      selectivity, specifically conversion close to 70%, selectivity close to 100% and
      TON of 113.6 for para-position electron-donating groups. The selectivity and eco
      friendliness of the biomimetic photocatalyst give it great potential for
      practical applications.

PMID- 29031451
TI  - A metal-free composite photocatalyst of graphene quantum dots deposited on red
      phosphorus.
AB  - A simple approach to enhance the photocatalytic activity of red phosphorus (P)
      was developed. A mechanical ball milling method was applied to reduce the size of
      red P and to deposit graphene quantum dots onto red P. The product was
      characterized by scanning electron microscopy, transmission electron microscopy,
      contact angle measurements, zeta-potential measurements, X-ray diffraction and UV
      vis absorption spectroscopy. The product exhibited high visible-light-driven
      photocatalytic performance in the photodegradation of rhodamine B.

PMID- 29031452
TI  - Construction of vesicle CdSe nano-semiconductors photocatalysts with improved
      photocatalytic activity: Enhanced photo induced carriers separation efficiency
      and mechanism insight.
AB  - Visible-light-driven photocatalysis as a green technology has attracted a lot of
      attention due to its potential applications in environmental remediation. Vesicle
      CdSe nano-semiconductor photocatalyst are successfully prepared by a gas template
      method and characterized by a variety of methods. The vesicle CdSe nano
      semiconductors display enhanced photocatalytic performance for the degradation of
      tetracycline hydrochloride, the photodegradation rate of 78.824% was achieved by
      vesicle CdSe, which exhibited an increase of 31.779% compared to granular CdSe.
      Such an exceptional photocatalytic capability can be attributed to the unique
      structure of the vesicle CdSe nano-semiconductor with enhanced light absorption
      ability and excellent carrier transport capability. Meanwhile, the large surface
      area of the vesicle CdSe nano-semiconductor can increase the contact probability
      between catalyst and target and provide more surface-active centers. The
      photocatalytic mechanisms are analyzed by active species quenching. It indicates
      that h+ and O2- are the main active species which play a major role in catalyzing
      environmental toxic pollutants. Simultaneously, the vesicle CdSe nano
      semiconductor had high efficiency and stability.

PMID- 29031453
TI  - Whole-genome comparison of urinary pathogenic Escherichia coli and faecal
      isolates of UTI patients and healthy controls.
AB  - The faecal flora is a common reservoir for urinary tract infection (UTI), and
      Escherichia coli (E. coli) is frequently found in this reservoir without causing
      extraintestinal infection. We investigated these E. coli reservoirs by whole
      genome sequencing a large collection of E. coli from healthy controls (faecal),
      who had never previously had UTI, and from UTI patients (faecal and urinary)
      sampled from the same geographical area. We compared MLST types, phylogenetic
      relationship, accessory genome content and FimH type between patient and control
      faecal isolates as well as between UTI and faecal-only isolates, respectively.
      Comparison of the accessory genome of UTI isolates to faecal isolates revealed 35
      gene families which were significantly more prevalent in the UTI isolates
      compared to the faecal isolates, although none of these were unique to one of the
      two groups. Of these 35, 22 belonged to a genomic island and three putatively
      belonged to a type VI secretion system (T6SS). MLST types and SNP phylogeny
      indicated no clustering of the UTI or faecal E. coli from patients distinct from
      the control faecal isolates, although there was an overrepresentation of UTI
      isolates belonging to clonal lineages CC73 and CC12. One combination of mutations
      in FimH, N70S/S78N, was significantly associated to UTI, while phylogenetic
      analysis of FimH and fimH identified no signs of distinct adaptation of UTI
      isolates compared to faecal-only isolates not causing UTI. In summary, the
      results showed that (i) healthy women who had never previously had UTI carried
      faecal E. coli which were overall closely related to UTI and faecal isolates from
      UTI patients; (ii) UTI isolates do not cluster separately from faecal-only
      isolates based on SNP analysis; and (iii) 22 gene families of a genomic island,
      putative T6SS proteins as well as specific metabolism and virulence associated
      proteins were significantly more common in UTI isolates compared to faecal-only
      isolates and (iv) evolution of fimH for these isolates was not linked to the
      clinical source of the isolates, apart from the mutation combination N70S/S78N,
      which was correlated to UTI isolates of phylogroup B2. Combined, these findings
      illustrate that faecal and UTI isolates, as well as faecal-only and faecal-UTI
      isolates, are closely related and can only be distinguished, if at all, by their
      accessory genome.

PMID- 29031454
TI  - A new plasma biomarker enhance the clinical prediction of postoperative acute
      kidney injury in patients with hepatocellular carcinoma.
AB  - BACKGROUND: The ratio of serum gamma-glutamyl transferase (GGT) to alanine
      aminotransferase (ALT) (GGT/ALT) is a marker for evaluating effects to
      antivirotic treatment and a helpful predictive factor for the prognosis of Child
      Pugh A hepatocellular carcinoma (HCC) patients after surgery. The relationship
      between the incidence of postoperative acute kidney injury (AKI) and preoperative
      GGT/ALT is studied in hepatectomized hepatitis B- or C- associated HCC patients.
      METHODS: A total of 253 hepatitis B or C virus-related HCC patients undergoing
      hepatectomy between September 2012 and August 2016 at our hospital were included
      in the retrospective study. Serum ALT and GGT value were recorded, and the
      GGT/ALT was computed. AKI was defined that based on the "Kidney Disease Improving
      Global Outcomes (KDIGO) criteria". RESULTS: AKI was observed in 22 (8.7%)
      patients. Mean GGT/ALT of patients with AKI was significantly higher than in
      those without it (6.0 vs 2.1, P<0.001). Multivariate analysis revealed an
      increase in GGT/ALT as an independent risk factor for AKI in hepatitis B- or C-
      associated HCC patients, particularly in patients with Barcelona Clinic Liver
      Cancer (BCLC) stage 0 or A staged HCC (odds ratio (OR) 1.400, P<0.001).
      Multivariate analysis showed that ALT (OR 0.966, P=0.044) was somewhat inversely
      associated with the incidence of AKI in hepatitis B- or C- associated HCC
      patients. The best cutoff point of GGT/ALT was 2.92. Multivariate analysis showed
      that preoperative GGT/ALT >=2.92 predicted poor prognosis of postoperative AKI in
      patients with HCC after hepatectomy (odds ratio 17.697, P<0.001). After
      propensity score matching, preoperative GGT/ALT >=2.92 remained an independent
      risk factor for AKI in HCC patients (OR 13.947, P=0.003). CONCLUSIONS: The
      GGT/ALT of patients with AKI was significantly higher than those without it.
      Evaluation of GGT/ALT before surgery can be a helpful predictive tool for
      postoperative AKI in hepatitis B- or C- associated HCC patients undergoing
      hepatectomy, particularly in patients with BCLC stage 0 or A staged HCC.
      Hepatitis B- or C- associated HCC patients with low ALT especially within the
      normal range may have a high risk of AKI. However, the reason remains to be
      elucidated.

PMID- 29031455
TI  - Does permanent atrial fibrillation modify response to cardiac resynchronization
      therapy in heart failure patients?
AB  - INTRODUCTION: The benefits of cardiac resynchronization therapy (CRT) documented
      in heart failure (HF) may be influenced by atrial fibrillation (AF). We aimed to
      compare CRT response in patients in AF and in sinus rhythm (SR). METHODS: We
      prospectively studied 101 HF patients treated by CRT. Rates of clinical,
      echocardiographic and functional response, baseline NYHA class and variation,
      left ventricular ejection fraction, volumes and mass, atrial volumes,
      cardiopulmonary exercise test (CPET) duration (CPET dur), peak oxygen consumption
      (VO2max) and ventilatory efficiency (VE/VCO2 slope) were compared between AF and
      SR patients, before and at three and six months after implantation of a CRT
      device. RESULTS: All patients achieved >=95% biventricular pacing, and 5.7%
      underwent atrioventricular junction ablation. Patients were divided into AF
      (n=35) and SR (n=66) groups; AF patients were older, with larger atrial volumes
      and lower CPET dur and VO2max before CRT. The percentages of clinical and
      echocardiographic responders were similar in the two groups, but there were more
      functional responders in the AF group (71% vs. 39% in SR patients; p=0.012). In
      SR patients, left atrial volume and left ventricular mass were significantly
      reduced (p=0.015 and p=0.021, respectively), whereas in AF patients, CPET dur
      (p=0.003) and VO2max (p=0.001; 0.083 age-adjusted) showed larger increases.
      CONCLUSION: Clinical and echocardiographic response rates were similar in SR and
      AF patients, with a better functional response in AF. Improvement in left
      ventricular function and volumes occurred in both groups, but left ventricular
      mass reduction and left atrial reverse remodeling were seen exclusively in SR
      patients (ClinicalTrials.gov identifier: NCT02413151; FCT code:
      PTDC/DES/120249/2010).

PMID- 29031456
TI  - Reply to the Letter to the Editor: "A peripheral comment".

PMID- 29031457
TI  - Microvalve controlled multi-functional microfluidic chip for divisional cell co
      culture.
AB  - Pneumatic micro-valve controlled microfluidic chip provides precise fluidic
      control for cell manipulation. In this paper, a multi-functional microfluidic
      chip was designed for three separate experiments: 1. Different cell lines were
      dispensed and cultured; 2. Three transfected SH-SY5Y cells were introduced and
      treated with methyl-phenyl-pyridinium (MPP+) as drug delivery mode; 3. Specific
      protection and interaction were observed among cell co-culture after nerve
      damage. The outcomes revealed the potential and practicability of our entire
      multi-functional pneumatic chip system on different cell biology applications.

PMID- 29031458
TI  - Quiet eye training improves accuracy in basketball field goal shooting.
AB  - University students (N = 240) were randomly assigned to a quiet eye training
      (QET) or technical training (TT) group, and their shooting accuracy (%)
      determined during a pre-, post-, and transfer test in basketball field shooting.
      Both groups first received lectures on visuomotor processing and the quiet eye
      (QE), followed by a laboratory in which participants in the QET group were taught
      how to adopt the QE characteristics of elite free-throw shooters, which stresses
      optimal gaze control and focus relative to a single target location, while the TT
      participants were taught elite biomechanics which stresses optimal control of the
      shooting stance, arms, and hands. Overall, the QET group's accuracy was
      significantly higher than the TT group, but differences were found due to skill
      level and defensive pressure. From pre to post, the accuracy of the QET novices
      increased significantly compared to the TT novices, but declined during transfer.
      Both the QET and TT intermediates had relatively high accuracy scores during the
      pre- and posttests, which then declined, as expected, during the transfer test
      against defensive pressure. However, during transfer the QET group's accuracy
      remained higher than the TT group and was surprisingly similar to that found in
      elite competition. It is recommended that novice and intermediate basketball
      players be taught how to adopt the QE of elite players, rather than learning only
      the technical/mechanical aspects of shooting. Theoretically, the study is placed
      within the context of top-down "cognitive control," as proposed by Cavanagh and
      Frank (2014), and QET studies which show that when learners are taught how to
      adopt the QE of elite performers, this appears to contribute to a more optimal
      organization of the neural networks underlying control of the task which, in
      turn, leads to improved shooting performance.

PMID- 29031459
TI  - Effectiveness of above real-time training on decision-making in elite football: A
      dose-response investigation.
AB  - We examined the effects of video-based training in elite footballers' decision
      making by presenting videos with training and testing scenarios at above real
      time speeds. We also examined different training protocols to establish how much
      training is beneficial. We found that above real-time training improved accuracy
      and response time in football decision-making. In terms of scheduling, we found
      that the benefits were short lasting and did not last beyond 2 weeks.

PMID- 29031460
TI  - Can athletes benefit from difficulty? A systematic review of growth following
      adversity in competitive sport.
AB  - Research points to the notion that athletes have the potential to benefit from
      difficulty. This phenomenon-otherwise known as growth following adversity-has
      attracted increasing attention from sport psychology scholars. In this paper, we
      systematically review and synthesize the findings of studies in this area to
      better understand: (a) how growth has been conceptualized in competitive sport,
      (b) the theory underpinning the study of growth in sport performers, (c) the
      nature of research conducted in this area, and (d) the adversity- and growth
      related experiences of competitive athletes. Following the application of
      inclusion criteria and methodological quality assessment, 17 studies were deemed
      suitable for inclusion in the systematic review. The findings of these studies
      are reviewed and synthesized in relation to study characteristics (viz. growth
      terminology, theoretical underpinning, study design, participant details, and
      data analysis), quality appraisal, adversity-related experiences (viz. negative
      events and experiences, and response to negative events and experiences), and
      growth-related experiences (viz. mechanisms of growth and indicators of growth).
      To facilitate understanding of growth following adversity in competitive sport,
      we address the definitions and theories that have informed the body of research,
      discuss the associated findings related to the adversity- and growth-related
      experiences of competitive athletes, and outline avenues for future research. It
      is hoped that this review and synthesis will facilitate understanding and inform
      practice in this area.

PMID- 29031461
TI  - Sleep, sport, and the brain.
AB  - The recognition that sleep is one of the foundations of athlete performance is
      increasing both in the elite athlete arena as well as applied performance
      research. Sleep, as identified through sleep deprivation and sleep extension
      investigations, has a role in performance, illness, injury, metabolism,
      cognition, memory, learning, and mood. Elite athletes have been identified as
      having poorer quality and quantity of sleep in comparison to the general
      population. This is likely the result on training times, competition
      stress/anxiety, muscle soreness, caffeine use, and travel. Sleep, in particular
      slow wave sleep, provides a restorative function to the body to recover from
      prior wakefulness and fatigue by repairing processes and restoring energy. In
      addition, research in the general population is highlighting the importance of
      sleep on neurophysiology, cognitive function, and mood which may have
      implications for elite athlete performance. It is thus increased understanding of
      both the effects of sleep deprivation and potential mechanisms of influence on
      performance that may allow scientists and practitioners to positively influence
      sleep in athletes and ultimately maximize performances.

PMID- 29031462
TI  - Effects of acute high-intensity exercise on cognitive performance in trained
      individuals: A systematic review.
AB  - BACKGROUND: High-intensity exercise is generally considered to have detrimental
      effects on cognition. However, high fitness levels are suggested to alleviate
      this effect. OBJECTIVES: The specific objective of this review was to evaluate
      the literature on the effect of acute high-intensity exercise on cognitive
      performance in trained individuals. METHODS: Studies were sourced through
      electronic databases, reference lists of retrieved articles, and manual searches
      of relevant reviews. Included studies examined trained participants, included a
      high-intensity exercise bout, used a control or comparison group/condition, and
      assessed cognitive performance via general laboratory tasks during or <=10min
      following exercise cessation. RESULTS: Ten articles met the inclusion criteria.
      Results indicated that the effect of acute high-intensity exercise on cognitive
      performance in trained individuals is dependent on the specific cognitive domain
      being assessed. Generally, simple tasks were not affected, while the results on
      complex tasks remain ambiguous. Accuracy showed little tendency to be influenced
      by high-intensity exercise compared to measures of speed. CONCLUSION: Multiple
      factors influence the acute exercise-cognition relationship and thus future
      research should be highly specific when outlining criteria such as fitness
      levels, exercise intensity, and exercise mode. Furthermore, greater research is
      needed assessing more cognitive domains, greater exercise durations/types, and
      trained populations at high intensities.

PMID- 29031463
TI  - Changes in brain activity during action observation and motor imagery: Their
      relationship with motor learning.
AB  - Many studies have demonstrated that training utilizing action observation and/or
      motor imagery improves motor performance. These two techniques are widely used in
      sports and in the rehabilitation of movement-related disorders. Motor imagery has
      also been used for brain-machine/computer interfaces (BMI/BCI). During both
      action observation and motor imagery, motor-related regions such as the premotor
      cortex and inferior parietal lobule are activated. This is common to actual
      execution and are involved with the underlying mechanisms of motor learning
      without execution. Since it is easier to record brain activity during action
      observation and motor imagery than that during actual sport movements, action
      observation, and motor imagery of sports skills or complex whole body movements
      have been utilized to investigate how neural mechanisms differ across the
      performance spectrum ranging from beginner to expert. However, brain activity
      during action observation and motor imagery is influenced by task complexity
      (i.e., simple vs complex movements). Furthermore, temporal changes in brain
      activity during actual execution along the long time course of motor learning are
      likely nonlinear and would be different from that during action observation or
      motor imagery. Activity in motor-related regions during action observation and
      motor imagery is typically greater in experts than in nonexperts, while the
      activity during actual execution is often smaller in experts than in nonexperts.

PMID- 29031464
TI  - Moving concussion care to the next level: The emergence and role of concussion
      clinics in the UK.
AB  - Concussion is a worldwide issue in sports medicine at present, and in recent
      years has evolved into a major consideration for sports in the United Kingdom
      (UK). Governing bodies, sports clinicians, and indeed athletes themselves are
      dealing with the implications that this injury brings. In parallel with this,
      innovative means of managing this condition are emerging. The creation of
      specialized concussion clinics (which mirror those present in the United States
      and Canada) is one means of enhancing concussion care in the UK. In this chapter,
      the emergence of concussion clinics in the UK will be discussed. The specific
      roles of the multidisciplinary teams working in these clinics will be outlined
      (including the disciplines of sports medicine, radiology, neurology,
      physiotherapy, and psychology/psychiatry), and the approaches used in the
      management of concussion in this setting will be explored. Future recommendations
      for the growth and development of clinic-based concussion care in the UK will
      also be discussed.

PMID- 29031465
TI  - Neurocognitive mechanisms of the flow state.
AB  - While the experience of flow is often described in attentional terms-focused
      concentration or task absorption-specific cognitive mechanisms have received
      limited interest. We propose that an attentional explanation provides the best
      way to advance theoretical models and produce practical applications, as well as
      providing potential solutions to core issues such as how an objectively difficult
      task can be subjectively effortless. Recent research has begun to utilize brain
      imaging techniques to investigate neurocognitive changes during flow, which
      enables attentional mechanisms to be understood in greater detail. Some tensions
      within flow research are discussed; including the dissociation between
      psychophysiological and experiential measures, and the equivocal neuroimaging
      findings supporting prominent accounts of hypofrontality. While flow has received
      only preliminary investigation from a neuroscientific perspective, findings
      already provide important insights into the crucial role played by higher-order
      attentional networks, and clear indications of reduced activity in brain regions
      linked to self-referential processing. The manner in which these processes may
      benefit sporting performance are discussed.

PMID- 29031466
TI  - Discerning measures of conscious brain processes associated with superior early
      motor performance: Capacity, coactivation, and character.
AB  - This study explored the relationship between working memory (WM) capacity,
      corticocortical communication (EEG coherence), and propensity for conscious
      control of movement during the performance of a complex far-aiming task. We were
      specifically interested in the role of these variables in predicting motor
      performance by novices. Forty-eight participants completed (a) an assessment of
      WM capacity (an adapted Rotation Span task), (b) a questionnaire that assessed
      the propensity to consciously control movement (the Movement Specific
      Reinvestment Scale), and (c) a hockey push-pass task. The hockey push-pass task
      was performed in a single task (movement only) condition and a combined task
      (movement plus decision) condition. Electroencephalography (EEG) was used to
      examine brain activity during the single task. WM capacity best predicted single
      task performance. WM capacity in combination with T8-Fz coherence (between the
      visuospatial and motor regions of the brain) best predicted combined task
      performance. We discuss the implied roles of visuospatial information processing
      capacity, neural coactivation, and propensity for conscious processing during
      performance of complex motor tasks.

PMID- 29031467
TI  - Action-skilled observation: Issues for the study of sport expertise and the
      brain.
AB  - With a growing body of research devoted to uncovering regions of the brain
      implicated in action observation following various action-related experiences,
      including sport, we ask what we know from this research, and what we still need
      to know, as it pertains to sport and the brain. To do this, we review and
      integrate knowledge garnered from developmental work, short-term motor learning
      studies, and most significantly sport athletes across varying skill levels. We
      consider various neurophysiological methods, including TMS, fMRI, and EEG, which
      have been used to help uncover brain regions involved in action-skilled
      observation. We are particularly interested in how these processes are related to
      action prediction and the detection of deceptive actions among athlete groups.
      This research is considered within broad theoretical frameworks related to action
      simulation and prediction, although our main focus is on the brain regions that
      have been implicated in skilled action observation and the implications of this
      research for knowledge and further study of sport expertise.

PMID- 29031468
TI  - Gunslingers, poker players, and chickens 1: Decision making under physical
      performance pressure in elite athletes.
AB  - BACKGROUND: The cognitive skills required during sport are highly demanding;
      accurate decisions based on the processing of dynamic environments are made in a
      fraction of a second (Walsh, 2014). Optimal decision-making abilities are crucial
      for success in sporting competition (Bar-Eli et al., 2011; Kaya, 2014). Moreover,
      for the elite athlete, decision making is required under conditions of intense
      mental and physical pressure (Anshel and Wells, 2000), yet much of the work in
      this area has largely ignored the highly stressful context in which athletes
      operate. A number of studies have shown that conditions of elevated pressure
      influence athletes' decision quality (Kinrade et al., 2015; Smith et al., 2016),
      response times (Hepler, 2015; Smith et al., 2016) and risk taking (Pighin et al.,
      2015). However, almost all of this work has been undertaken in nonelite athletes
      and participants who do not routinely operate under conditions of high stress.
      Thus, there is very little known about the influence of pressure on decision
      making in elite athletes. OBJECTIVE: This study investigated the influence of
      physical performance pressure on decision making in a sample of world-class elite
      athletes. This allowed an examination of whether findings from the previous work
      in nonelite athletes extend to those who routinely operate under conditions of
      high stress. How this work could be applied to improve insight and understanding
      of decision making among sport professionals is examined. We sought to introduce
      a categorization of decision making useful to practitioners in sport:
      gunslingers, poker players, and chickens. METHODS: Twenty-three elite athletes
      who compete and have frequent success at an international level (including six
      Olympic medal winners) performed tasks relating to three categories of decision
      making under conditions of low and high physical pressure. Decision making under
      risk was measured with performance on the Cambridge Gambling Task (CGT; Rogers et
      al., 1999), decision making under uncertainty with the Balloon Analogue Risk Task
      (BART; Lejuez et al., 2002), and fast reactive responses and interference with
      the Stroop Task (Stroop, 1935). Performance pressures of physical exhaustion was
      induced via an exercise protocol consisting of intervals of maximal exertion
      undertaken on a watt bike. RESULTS: At a group level, under physical pressure
      elite athletes were faster to respond to control trials on the Stroop Task and to
      simple probabilistic choices on the CGT. Physical pressure was also found to
      increase risk taking for decisions where probability outcomes were explicit (on
      the CGT), but did not affect risk taking when probability outcomes were unknown
      (on the BART). There were no significant correlations in the degree to which
      individuals' responses changed under pressure across the three tasks, suggesting
      that elite athletes did not show consistent responses to physical pressure across
      measures of decision making. When assessing the applicability of results based on
      group averages to individual athletes, none of the sample showed an "average"
      response (within 1 SD of the mean) to pressure across all three decision-making
      tasks. CONCLUSION: There are three points of conclusion. First, an immediate
      scientific point that highlights a failure of transfer of work reported from
      nonelite athletes to elite athletes in the area of decision making under
      pressure. Second, a practical conclusion with respect to the application of this
      work to the elite sporting environment, which highlights the limitations of
      statistical approaches based on group averages and thus the beneficial use of
      individualized profiling in feedback sessions. Third, the application of this
      work in a sports setting is described, in particular the development and
      implementation of a decision-making taxonomy as a framework to conceptualize and
      communicate psychological skills among elite sporting professionals.

PMID- 29031469
TI  - Gunslingers, poker players, and chickens 2: Decision-making under physical
      performance pressure in subelite athletes.
AB  - BACKGROUND: Having investigated the influence of acute physical exhaustion on
      decision-making in world-class elite athletes in Parkin et al. (2017), here a
      similar method is applied to subelite athletes. These subelite athletes were
      enrolled on a Team GB talent development program and were undergoing training for
      possible Olympic competition in 4-8 years. They differ from elite athletes
      examined previously according to expertise and age. While considered elite (Swann
      et al., 2015), the subelite athletes had approximately 8 years fewer sporting
      experience and were yet to obtain sustained success on the international stage.
      Additionally, the average age of the subelite sample is 20 years; thus, they are
      still undergoing the behavioral, cognitive, and neuronal changes that occur
      during the transition from late adolescence to young adulthood (Blakemore and
      Robbins, 2012). Previous work has used broad definitions of elite status in
      sport, and as such overlooked different categories within the spectrum of elite
      athletes (Swann et al., 2015). Therefore it is important to consider subelite
      athletes as a discrete point on the developmental trajectory of elite sporting
      expertise. OBJECTIVE: This work aims to investigate the influence of physical
      pressure on key indicators of decision-making in subelite athletes. It forms part
      of a wider project examining decision-making across different stages of the
      developmental trajectory in elite sport. In doing so, it aims to examine how to
      apply and develop psychological insights useful to an elite sporting environment.
      METHODS: 32 subelite athletes (18 males, mean age: 20 years) participated in the
      study. Performance across three categories of decision-making was assessed under
      conditions of low and high physical pressure. Decision-making under risk was
      measured with performance of the Cambridge Gambling Task (CGT; Rogers et al.,
      1999), decision-making under uncertainty with the Balloon Analogue Risk Task
      (BART; Lejuez et al., 2002), and fast reactive responses and inhibition via the
      Stop Signal Reaction Time Task (SSRT; Logan, 1994). Physical exhaustion was
      induced via intervals of maximal exertion exercise on a wattbike. RESULTS: Under
      pressure subelite athletes showed increased risk taking for both decisions where
      probability outcomes were explicit (on the CGT), and those where probability
      outcomes were unknown (on the BART). Despite making quicker decisions under
      pressure, with fewer errors, on the CGT, subelite athletes showed a reduced
      ability to optimally adjust betting behavior according to reward and loss
      contingencies. Fast reactive responses to perceptual stimuli and response
      inhibition did not change as a result of physical pressure. Individual responses
      to pressure showed a negative correlation in that a decrease in reaction times on
      the SSRT Task under pressure was associated with an increase in risk taking on
      the BART. When assessing the applicability of results based on group averages to
      individual athletes, 17% of the sample showed an "average" response (within 1 SD
      of the mean) to pressure across all three decision-making tasks. CONCLUSION:
      Indicators of decision-making in a sample of subelite athletes are influenced by
      physical pressure, with a shift toward increased indiscriminate risk taking. The
      influence that physical pressure has on decision-making was different to that
      observed in world-class elite athletes; this highlights the importance of
      distinguishing between athletes at the elite level (Swann et al., 2015). The
      application of this work to a novel subgroup of elite athletes, including the
      implementation of a decision-making taxonomy, is discussed.

PMID- 29031470
TI  - The resonant system: Linking brain-body-environment in sport performance?.
AB  - The ecological dynamics approach offers new insights to understand how athlete
      nervous systems are embedded within the body-environment system in sport.
      Cognitive neuroscience focuses on the neural bases of athlete behaviors in terms
      of perceptual, cognitive, and motor functions defined within specific brain
      structures. Here, we discuss some limitations of this traditional perspective,
      addressing how athletes functionally adapt perception and action to the dynamics
      of complex performance environments by continuously perceiving information to
      regulate goal-directed actions. We examine how recent neurophysiological evidence
      of functioning in diverse cortical and subcortical regions appears more
      compatible with an ecological dynamics perspective, than traditional views in
      cognitive neuroscience. We propose how athlete behaviors in sports may be related
      to the tuning of resonant mechanisms indicating that perception is a dynamic
      process involving the whole body of the athlete. We emphasize the important role
      of metastable dynamics in the brain-body-environment system facilitating
      continuous interactions with a landscape of affordances (opportunities for
      action) in a performance environment. We discuss implications of these ideas for
      performance preparation and practice design in sport.

PMID- 29031471
TI  - Gunslingers, poker players, and chickens 3: Decision making under mental
      performance pressure in junior elite athletes.
AB  - BACKGROUND: Having investigated the decision making of world class elite and
      subelite athletes (see Parkin and Walsh, 2017; Parkin et al., 2017), here the
      abilities of those at the earliest stage of entry to elite sport are examined.
      Junior elite athletes have undergone initial national selection and are younger
      than athletes examined previously (mean age 13 years). Decision making under
      mental pressure is explored in this sample. During performance an athlete
      encounters a wide array of mental pressures; these include the psychological
      impact of errors, negative feedback, and requirements for sustained attention in
      a dynamic environment (Anshel and Wells, 2000; Mellalieu et al., 2009). Such
      factors increase the cognitive demands of the athletes, inducing distracting
      anxiety-related thoughts known as rumination (Beilock and Gray, 2007). Mental
      pressure has been shown to reduce performance of decision-making tasks where
      reward and loss contingencies are explicit, with a shift toward increased risk
      taking (Pabst et al., 2013; Starcke et al., 2011). Mental pressure has been shown
      to be detrimental to decision-making speed in comparison to physical stress,
      highlighting the importance of considering a range of different pressures
      encountered by athletes (Hepler, 2015). OBJECTIVE: To investigate the influence
      of mental pressure on key indicators of decision making in junior elite athletes.
      This chapter concludes a wider project examining decision making across
      developmental stages in elite sport. The work further explores how psychological
      insights can be applied in an elite sporting environment and in particular
      tailored to the requirements of junior athletes. METHODS: Seventeen junior elite
      athletes (10 males, mean age: 13.80 years) enrolled on a national youth athletic
      development program participated in the study. Performance across three
      categories of decision making was assessed under conditions of low and high
      mental pressure. Decision making under risk was measured via the Cambridge
      Gambling Task (CGT; Rogers et al., 1999), decision making under uncertainty via
      the Balloon Analogue Risk Task (BART; Lejuez et al., 2002), and fast reactive
      responses to perceptual stimuli via the Visual Search Task (Treisman, 1982).
      Mental pressure was induced with the addition of a concurrent verbal memory task,
      used to increase cognitive load and mimic the distracting effects of anxiety
      related rumination. RESULTS: In junior elite athletes, fast reactive responses to
      perceptual stimuli (on the Visual Search Task) were slower under conditions of
      mental pressure. For decision making under risk there was an interaction of
      mental pressure and gender on the amount of points gambled, under pressure there
      was a higher level of risk taking in male athletes compared to females. There was
      no influence of mental pressure on decision making under uncertainity. There were
      no significant correlations in the degree to which individual's responses changed
      under pressure across the three measures of decision making. When assessing the
      applicability of results based on group averages there were no junior elite
      athletes who showed an "average" response (within 1SD of the mean) to mental
      pressure across all the three decision-making tasks. CONCLUSION: Mental pressure
      affects decision making in a sample of junior elite athletes, with a slowing of
      response times, and modulations to performance of decision making under risk that
      have a high requirement for working memory. In relation to sport, these findings
      suggest that novel situations that place high cognitive demands on the athlete
      may be particularly influenced by mental pressure. The application of this work
      in junior elite athletes included the feedback of individual results and the
      implementation of a decision-making taxonomy.

PMID- 29031472
TI  - Catching on it early: Bodily and brain anticipatory mechanisms for excellence in
      sport.
AB  - Programming and executing a subsequent move is inherently linked to the ability
      to anticipate the actions of others when interacting. Such fundamental social
      ability is particularly important in sport. Here, we discuss the possible
      mechanisms behind the highly sophisticated anticipation skills that characterize
      experts. We contend that prediction in sports might rely on a finely tuned
      perceptual system that endows experts with a fast, partially unconscious, pickup
      of relevant cues. Furthermore, we discuss the role of the multimodal,
      perceptuomotor, multiple-duty cells (mirror neurons) that play an important
      function in action anticipation by means of an inner motor simulation process.
      Finally, we suggest the role of predictive coding, interoception, and the enteric
      nervous system as the processual and biological support for intuition and "gut
      feelings" in sports-the missing link that might explain outstanding expert
      performance based on action anticipation.

PMID- 29031473
TI  - Exploring the applicability of the contextual interference effect in sports
      practice.
AB  - This review will consider three key issues considered critical when determining
      the efficacy of the contextual interference effect when applied to sports
      practice. First, the issue of complexity is considered in relation to the amount
      of interference actually needed in the applied sports setting to create effective
      learning. Second, the traditional underpinning mechanism/s of contextual
      interference are discussed in relation to recent neurophysiological perspectives
      on their viability. A counter-position to these dominant theories is also
      presented drawing on an implicit learning framework. The final issue considers
      the typical measures of learning used within the contextual interference
      literature and scrutinizes them relative to the needs of bridging the apparent
      theory-practice divide. The concluding section then presents a model to measure
      the degree of contextual interference within the applied setting, which in turn
      offers both future research directions as well as guidelines for practitioners.

PMID- 29031474
TI  - Sport, time pressure, and cognitive performance.
AB  - Sport participation, fitness, and expertise have been associated with a range of
      cognitive benefits in a range of populations but both the factors that confer
      such benefits and the nature of the resulting changes are relatively unclear.
      Additionally, the interactions between time pressure and cognitive performance
      for these groups is little studied. Using a flanker task, which measures the
      ability to selectively process information, and with different time limits for
      responding, we investigated the differences in performance for participants in
      (1) an unpredictable, open-skill sport (volleyball), (2) an exercise group
      engaged in predictable, closed-skill sports (running, swimming), and (3)
      nonsporting controls. Analysis by means of a drift diffusion analysis of response
      times was used to characterize the nature of any differences. Volleyball players
      were more accurate than controls and the exercise group, particularly for shorter
      time limits for responding, as well as tending to respond more quickly. Drift
      diffusion model analysis suggested that better performance by the volleyball
      group was due to factors such as stimulus encoding or motor programming and
      execution rather than decision making. Trends in the pattern of data seen also
      suggest less noisy cognitive processing (rather than greater efficiency) and
      should be further investigated.

PMID- 29031475
TI  - Natural infection of croton yellow vein mosaic virus and its cognate
      betasatellite in germplasm of different Crambe spp in India.
AB  - Crambe is an important crop grown worldwide for industrial oil and seed meal.
      Besides the fungal and bacterial diseases, the crop is reported to be infected by
      tobacco mosaic virus, beet western yellows virus and turnip mosaic virus under
      experimental condition. Till now, there was no report of natural infection of any
      begomovirus in this crop. In the present study, a leaf curl disease was observed
      in germplasm accessions of three species of Crambe (C. abyssinica, C. glabrata
      and C. hispanica). Based on the symptoms and presence of whitefly population in
      the field, begomovirus infection was suspected. Molecular characterization
      through RCA approach, indicated presence of croton yellow vein mosaic virus
      (CYVMV, KJ747958) and croton yellow vein mosaic betasatellite (CroYVMB,
      KM229762). Co-agroinoculation of partial dimeric construct of CYVMV with complete
      dimeric construct of CroYVMB, produced typical leaf curl symptoms in C.
      abyssinica, whereas, agroinoculation of partial dimeric construct of CYVMV alone
      could not produce symptoms in the same plant. In contrast, the CYVMV construct
      alone could produce symptom in Nicotiana benthamiana, a model host for plant
      virus studies. In N. benthamiana co-inoculation of CroYVMV with CYVMV construct
      develop more severe symptoms. However, neither the CYVMV construct alone nor the
      co-inoculation with CroYVMB produce any symptom in Arabidopsis thaliana even with
      different methods of inoculation. Inoculated Arabidopsis thaliana also did not
      yield any amplification of the virus as assessed through PCR and rolling circle
      amplification (RCA). Thus it confirmed that for successful infection in crambe,
      CYVMV requires betasatellite, while in N. benthamiana, it does not require
      betasatellite for symptom induction and in Arabidopsis thaliana CYVMV alone or in
      presence of betasatellite did not replicate and produce any symptom. This study
      constitutes the first confirmed record of natural infection of a begomovirus in
      crambe and further confirmed that cognate betasatellite of CYVMV has differential
      role in infectivity in different hosts.

PMID- 29031476
TI  - IL-1beta upregulates Muc5ac expression via NF-kappaB-induced HIF-1alpha in
      asthma.
AB  - The manifest and important feature in respiratory diseases, including asthma and
      COPD (chronic obstructive pulmonary disease), is the increased numbers and
      hypersecretion of goblet cells and overexpression of mucins, especially Muc5ac.
      Many proinflammatory cytokines play important roles in goblet cell metaplasia and
      overproduction of Muc5ac. However, the effect of IL-1beta on Muc5ac expression in
      asthma remains unknown. Here, we detected the correlation between IL-1beta and
      Muc5ac in asthma patients and further explored the mechanism of IL-1beta-induced
      Muc5ac overexpression. Our results showed that Muc5ac and IL-1beta were up
      regulated in 41 patients with asthma and that Muc5ac overexpression was related
      with IL-1beta in asthma (R2=0.668, p?0.001). Furthermore, the correlation between
      IL-1beta and Muc5ac is higher in severe group than that in moderate group. In
      vitro experiments with normal human bronchial epithelial cells (NHBECs) showed
      that IL-1beta up-regulated Muc5ac expression in NHBEC in a time- and dosage
      dependent manner. Hypoxia-induced HIF-1alpha was responsible for Muc5ac
      expression mediated by IL-1beta. Knocking down HIF-1alpha by siRNA decreased
      Muc5ac expression under hypoxia even in IL-1beta-treated NHBEC cells. Luciferase
      reporter assay showed that HIF-1alpha enhanced Muc5ac promoter activity in
      HEK293T cells. HIF-1alpha could specifically bind to the promoter of Muc5ac by
      EMSA. The correlation among IL-1beta, HIF-1alpha and Muc5ac was observed in
      patients with asthma. Mechanically, NF-kappaB activation was essential to IL
      1beta-induced HIF-1alpha upregulation via the canonical pathway of NF-kappaB. The
      level of nuclear p65, a subunit of NF-kappaB, was obviously increased in NHBEC
      cells under IL-1beta treatment. IL-1beta did not change either HIF-1alpha or
      Muc5ac expression when inhibiting NF-kappaB signaling with Bay11-7082, an
      inhibitor of NF-kappaB. Collectively, we concluded that IL-1beta up-regulated
      Muc5ac expression via NF-kappaB-induced HIF-1alpha in asthma and provided a
      potential therapeutic target for asthma.

PMID- 29031477
TI  - Acute developmental exposure to 4-hydroxyandrostenedione has a long-term effect
      on visually-guided behaviors.
AB  - Estrogenic and anti-estrogenic endocrine disrupting compounds (EDCs) are
      recognized as critical modulators of neural development, including sensory system
      development. Using the zebrafish model, we tested the effect of transient
      developmental exposure to a known anti-estrogenic EDC on adult visually-guided
      behavior. In particular, we exposed zebrafish aged 24-hour post-fertilization
      (hpf), 72 hpf, or 7-days post-fertilization (dpf) to the aromatase inhibitor 4
      hydroxyandrostenedione (4-OH-A) for 24h. After this time, the fish were removed
      from treatment, placed into control conditions, and reared until adulthood (3
      4months) when visually-guided optomotor responses (OMR) were assessed. Our
      results show significant decreases in positive OMR in adults exposed to 4-OH-A at
      72 hpf and 7 dpf. These deficits were not accompanied by changes in overall
      swimming behaviors and startle responses, suggesting 4-OH-A specifically effected
      the visual system. Overall, this study identified long-term, quantifiable effects
      in visually-guided adult behaviors resulting from transient developmental
      exposure to the anti-estrogenic EDC, 4-OH-A. Further, these effects were noted
      when 4-OH-A exposure occurred after hatching, suggesting estrogen signaling is
      important for visual system maturation.

PMID- 29031478
TI  - Patterns of facial trauma before and after legalization of marijuana in Denver,
      Colorado: A joint study between two Denver hospitals.
AB  - INTRODUCTION: The effect of marijuana on human health has been studied
      extensively. Marijuana intoxication has been shown to affect performance,
      attention span, and reaction time. The public health relationship between trauma
      and cannabis use has also been studied, with mixed conclusions. In this report,
      the effect of marijuana legalization on many aspects of facial trauma at two
      hospitals in Denver, Colorado is examined. METHODS: A retrospective review of the
      electronic medical records was undertaken. Mann-Whitney U tests were used to
      compare age of patients before and after legalization, and chi squared analyses
      were used to compare mechanism of injury, and fracture types before and after
      recreational marijuana legalization in Denver, Colorado. Geographical location of
      patients was also considered. RESULTS: No significant increase was found in race
      before and after marijuana legalization (p=0.19). A significant increase in age
      was found before (M=39.54,SD=16.37), and after (M=41.38,SD=16.66) legalization
      (p<0.01). Maxillary and skull base fracture proportions significantly increased
      following legalization (p<0.001 and p<0.001respectively). No significant
      differences were seen in the proportion of patients who lived in urban and rural
      counties before and after legalization (p>0.05). CONCLUSION: Public health
      efforts should be directed towards educating residents and visitors of Colorado
      on the effects and toxicology of marijuana. More epidemiologic studies are needed
      for further assessment of the long-term effects of the legalization of marijuana
      on the population.

PMID- 29031479
TI  - The optimum chest compression site with regard to heart failure demonstrated by
      computed tomography.
AB  - BACKGROUND: To determine the optimum chest compression site during
      cardiopulmonary resuscitation (CPR) with regard to heart failure (HF) by applying
      three-dimensional (3D) coordinates on computed tomography (CT). METHODS: This
      retrospective, cross-sectional study involved adults who underwent
      echocardiography and CT on the same day from 2007 to 2017. Incomplete CT images
      or information on HF, cardiac medication between echocardiography and CT, or
      thoracic abnormalities were excluded. Cases were checked whether they had HF
      through symptom/sign assessment, N-terminal pro-B type natriuretic peptide, and
      echocardiography. We set the xiphisternal joint's midpoint as the reference (0,
      0, 0) to draw a 3D coordinate system, designating leftward, upward, and into-the
      thorax directions as positive. The coordinate of the maximum LV diameter's
      midpoint (P_max.LV) was identified. RESULTS: Enrolled were 148 patients (63.0+/
      15.1 years) with 87 females and 76 HF cases. P_max.LV of HF cases was located
      more leftwards, lower, and deeper than non-HF cases (5.69+/-0.98, -1.51+/-1.67,
      5.76+/-1.09 cm vs. 5.00+/-0.83, -0.99+/-1.36, 5.25+/-0.71 cm, all p<0.05). Fewer
      HF cases had their LV compressed than non-HF cases (59.2% vs. 77.8%, p=0.025)
      when being compressed according to the current guidelines. The aorta (vs. LV) was
      compressed in 85.5% and 81.9% of HF and non-HF cases, respectively, at 3 cm above
      the xiphisternal joint. At 6cm above the joint, the highest allowable position
      according to the current guidelines, all victims would have their aorta
      compressed directly during CPR rather than the LV. CONCLUSIONS: The lowest
      possible sternum just above the xiphisternal joint should be compressed
      especially for HF patients during CPR.

PMID- 29031480
TI  - More than a drink: A rare anaphylactic reaction to sparkling water.
AB  - Anaphylaxis is a potentially life threatening, type I hypersensitivity reaction
      which can occur within seconds to minutes after exposure to an allergen. Sulfites
      have been implicated in causing such reactions with symptoms ranging from mild to
      potentially life threatening. Here we present a patient who had an anaphylactic
      reaction secondary to exposure to sulfites found in sparkling water.

PMID- 29031481
TI  - Systemic lupus erythematosus following meningococcal vaccination.
AB  - Systemic erythematosus lupus (SLE) affects multiple organs and involves complex
      immune dysfunction. Because vaccinations are inherently designed to stimulate the
      immune response, they have been linked with increased risk for flare of SLE and
      other autoimmune disorders, and their association with new-onset autoimmune
      disease has been postulated in several case reports. To our knowledge, this is
      the first reported case of the meningococcal vaccine precipitating SLE in a
      previously undiagnosed patient. We present a case of a previously healthy, 17
      year old Asian female who presented to the ED with 14 days of fever and fatigue
      after administration of the meningococcal vaccine, as well as 5 days of facial
      rash. Initial labs showed pancytopenia, bandemia, proteinuria, elevated
      erythrocyte sedimentation rate, and elevated d-dimer. Both the antinuclear
      antibodies (ANA) and anti-double stranded DNA were positive and cervical
      lymphadenopathy was present. This case highlights the importance of considering
      acute autoimmune reactions such as SLE in the differential diagnosis when
      assessing previously healthy patients presenting with systemic symptoms such as
      fever and rash in the setting of recent vaccination.

PMID- 29031482
TI  - Toxicologic/transport properties of NCS-382, a gamma-hydroxybutyrate (GHB)
      receptor ligand, in neuronal and epithelial cells: Therapeutic implications for
      SSADH deficiency, a GABA metabolic disorder.
AB  - We report the in vitro assessment of pharmacotoxicity for the high-affinity GHB
      receptor ligand, NCS-382, using neuronal stem cells derived from mice with a
      targeted deletion of the aldehyde dehydrogenase 5a1 gene (succinic semialdehyde
      dehydrogenase(SSADH)-deficient mice). These animals represent a phenocopy of the
      human disorder of GABA metabolism, SSADH deficiency, that metabolically features
      accumulation of both GABA and the GABA-analog gamma-hydroxybutyric acid in
      conjunction with a nonspecific neurological phenotype. We demonstrate for the
      first time using MDCK cells that NCS-382 is actively transported and capable of
      inhibiting GHB transport. Following these in vitro assays with in vivo studies in
      aldh5a1-/- mice, we found the ratio of brain/liver GHB to be unaffected by
      chronic NCS-382 administration (300mg/kg; 7 consecutive days). Employing a
      variety of cellular parameters (reactive oxygen and superoxide species, ATP
      production and decay, mitochondrial and lysosomal number, cellular viability and
      necrosis), we demonstrate that up to 1mM NCS-382 shows minimal evidence of
      pharmacotoxicity. As well, studies at the molecular level indicate that the
      effects of NCS-382 at 0.5mM are minimally toxic as evaluated using gene
      expression assay. The cumulative data provides increasing confidence that NCS-382
      could eventually be considered in the therapeutic armament for heritable SSADH
      deficiency.

PMID- 29031483
TI  - DUOX expression in human keratinocytes and bronchial epithelial cells: Influence
      of vanadate.
AB  - Dual oxygenases (DUOX) 1 and 2, expressed in many animal tissues, participate in
      host defense at mucosal surfaces and may have important signaling roles through
      generation of reactive oxygen. Present work addresses their expression in
      cultured human epidermal keratinocytes and effects of cytokines and
      metal/metalloid compounds. Both DUOX1 and 2 were expressed at much higher levels
      after confluence than in the preconfluent state. Maximal DUOX1 mRNA levels were
      50 fold those of DUOX2. DUOX1 and 2 were induced ~3 fold by interleukin 4, but
      only DUOX1 was induced by interferon gamma (IFNgamma). In human bronchial HBE1
      cells, by contrast, interleukin 4 induced only DUOX 1, and IFNgamma induced only
      DUOX2. A survey in the keratinocytes of metal/metalloid compounds showed that
      arsenite, antimonite, chromate, cadmium, copper, lead and vanadate suppressed
      DUOX1 levels but did not prevent interleukin 4 stimulation. Effects on DUOX2 were
      less dramatic, except that vanadate potentiated the stimulation by IFNgamma up to
      7 fold. The results indicate that epithelial cell types of different tissue
      origins can differ in their cytokine regulation and that epidermal cells can
      exhibit striking alterations in response due to certain metal/metalloid
      exposures.

PMID- 29031484
TI  - Effects of leucine-enriched essential amino acid and whey protein bolus dosing
      upon skeletal muscle protein synthesis at rest and after exercise in older women.
AB  - BACKGROUND & AIMS: Impaired anabolic responses to nutrition and exercise
      contribute to loss of skeletal muscle mass with ageing (sarcopenia). Here, we
      tested responses of muscle protein synthesis (MPS), in the under represented
      group of older women, to leucine-enriched essential amino acids (EAA) in
      comparison to a large bolus of whey protein (WP). METHODS: Twenty-four older
      women (65 +/- 1 y) received (N = 8/group) 1.5 g leucine-enriched EAA supplements
      (LEAA_1.5), 6 g LEAA (LEAA_6) in comparison to 40 g WP. A primed constant I.V
      infusion of 13C6-phenylalanine was used to determine MPS at baseline and in
      response to feeding (FED) and feeding-plus-exercise (FED-EX; 6 * 8 unilateral leg
      extensions; 75%1-RM). We quantified plasma insulin/AA concentrations, leg femoral
      blood flow (LBF)/muscle microvascular blood flow (MBF), and anabolic signalling
      via immunoblotting. RESULTS: Plasma insulineamia and EAAemia were greater and
      more prolonged with WP than LEAA, although LEAA_6 peaked at similar levels to WP.
      Neither LEAA or WP modified LBF or MBF. FED increased MPS similarly in the
      LEAA_1.5, LEAA_6 and WP (P < 0.05) groups over 0-2 h, with MPS significantly
      higher than basal in the LEAA_6 and WP groups only over 0-4 h. However, FED-EX
      increased MPS similarly across all the groups from 0 to 4 h (P < 0.05). Only p
      p70S6K1 increased with WP at 2 h in FED (P < 0.05), and at 2/4 h in FED-EX (P <
      0.05). CONCLUSIONS: In conclusion, LEAA_1.5, despite only providing 0.6 g of
      leucine, robustly (perhaps maximally) stimulated MPS, with negligible trophic
      advantage of greater doses of LEAA or even to 40 g WP. Highlighting that
      composition of EAA, in particular the presence of leucine rather than amount is
      most crucial for anabolism.

PMID- 29031485
TI  - Allergic Contact Dermatitis by Anatomical Regions: Diagnostic Clues.
AB  - Allergic contact dermatitis (ACD) is a common disease in daily clinical practice,
      and its prevalence has increased in recent years. It is characterized clinically
      by varying degrees of erythema, vesiculation, flaking, and lichenification,
      though these signs can also be present in other eczematous diseases. Patch
      testing is the main diagnostic tool to confirm ACD, but its accurate
      interpretation requires correct correlation with the medical history (details of
      exposure) and physical examination. We provide a practical and instructive
      description of the most common clinical patters of ACD depending on the area
      affected. Knowledge of these patterns will not only help the clinician reach the
      diagnosis but will suggest possible allergens and forms of contact.

PMID- 29031486
TI  - Reply To: The Possible Combined Action of Different Trigger Agents in Rosacea.

PMID- 29031487
TI  - The Possible Combined Action of Different Trigger Agents in Rosacea.

PMID- 29031488
TI  - [Outcome of living kidney donors for transplantation].
AB  - Nowadays, several treatments exist to treat terminal chronic renal failure. Best
      results for the recipients are obtained with kidney transplantation concerning
      mortality and quality of life. Transplantation is also the cheaper option for
      society. Living kidney donation raises the issue of the becoming of the donor, an
      absolutely healthy subject who gets to a surgical procedure. The becoming of
      living kidney donors has been compared with the one of controls subjects in
      several studies. The evaluations focused on the complications of nephrectomy in
      the short and long-term: kidney failure, hypertension, proteinuria, possibility
      of pregnancy, quality of life, and mortality. The first results did not show any
      risk linked to kidney donation, compared to general population. However, since
      2013, kidney donors were found at higher risk for kidney failure and even for
      mortality, compared with controls selected like donor candidates. The risk of
      kidney donation is nevertheless acceptable and minimal, on the condition of
      rigorous selection of candidates and regular follow-up.

PMID- 29031489
TI  - [Pediatric nephrology: What should an adult nephrologist know about these
      diseases?]
AB  - In nephrology, some diseases begin specifically during childhood; however, they
      must be known by adult nephrologists so that to ensure continuity and homogeneity
      for their management. The aim of this review is therefore to propose a brief
      overview of the main pediatric diseases, for which a specific knowledge is
      warranted, and notably pediatric idiopathic nephrotic syndrome, cystinosis,
      primary hyperoxaluria and hereditaries tubulopathies.

PMID- 29031490
TI  - [Survey on the perception of competencies acquired during nephrology resident
      training in France].
AB  - Due to a national theoretical training provided to all resident for many years
      and the ongoing discussions to change the organization of the resident training
      of specialized study diploma (SSD) of nephrology, a survey was done to assess the
      perception of skills acquired in the management of different clinical situations
      in terms of knowledge, expertise and attitudes. The expected results are intended
      to identify new training procedures for future nephrologists in France. The study
      was performed in 112 resident from 3rd and 4th year of nephrology resident
      training attending an educational seminar of the University College of Nephrology
      Teachers in May 2014. The survey was conducted with a self-administered anonymous
      questionnaire to assess the perception of the acquisition of different skills.
      The results show a heterogeneity acquisition between different areas of skills
      suggesting possible improvement with development of outpatient activity or with
      training in specialized units such as for peritoneal dialysis or plasma exchange
      activity. Therefore, these findings suggest further structuring of the regional
      training and development of the simulation training to acquire the expertise and
      attitudes. Finally, the use of an evaluation book of skills acquired throughout
      the training could be interesting in the context of standardization of validating
      training of nephrologists as proposed in the reform of the SSD of nephrology.

PMID- 29031491
TI  - Measurement of absolute K X-ray emission intensities in the decay of 103mRh.
AB  - A new experiment was designed to measure the photon emission intensities in the
      decay of 103mRh. The rhodium samples were activated in the ISIS experimental
      nuclear reactor at CEA Saclay. The procedure includes an absolute activity
      measurement by liquid scintillation counting using the Triple-to-Double
      Coincidence Ratio method, followed by X-ray spectrometry using a high-purity
      germanium detector to determine the photon emission intensities. The new result
      (IX = 0.0825 (17)) is derived with a significant reduction of the uncertainty.

PMID- 29031492
TI  - Comprehensive vs. Assisted Management of Mood and Pain Symptoms (CAMMPS) trial:
      Study design and sample characteristics.
AB  - BACKGROUND: Pain is the most common presenting somatic symptom in medical
      outpatients, and depression and anxiety are the two most common mental disorders.
      They frequently co-occur, are under-treated, and result in substantial disability
      and reduced health-related quality of life. OBJECTIVES: The Comprehensive vs.
      Assisted Management of Mood and Pain Symptoms (CAMMPS) study is a randomized
      comparative effectiveness trial designed to test the relative effectiveness of a
      lower-resource vs. a higher-resource technology-assisted intervention for the
      management of patients suffering from pain plus anxiety and/or depression.
      METHODS/DESIGN: CAMMPS has enrolled 294 primary care patients with chronic pain
      plus comorbid anxiety and/or depression and randomized them to either: 1)
      Assisted Symptom Management (ASM) consisting of automated symptom monitoring by
      interactive voice recording or Internet and prompted pain and mood self
      management; or 2) Comprehensive Symptom Management (CSM) which combines ASM with
      optimized medication management delivered by a nurse-physician specialist team
      and facilitated mental health care. Outcomes are assessed at baseline, 1, 3, 6,
      and 12months. The primary outcome is a composite pain-anxiety-depression (PAD)
      severity score. Secondary outcomes include individual pain, anxiety, and
      depression scores, health-related quality of life, disability, healthcare
      utilization, and treatment satisfaction. DISCUSSION: CAMMPS provides an
      integrated approach to PAD symptoms rather than fragmented care of single
      symptoms; coordinated symptom management in partnership with primary care
      clinicians and psychologists embedded in primary care; efficient use of health
      information technology; attention to physical and psychological symptom
      comorbidity; and the coupling of self-management with optimized medication
      management and facilitated mental health care. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01757301.

PMID- 29031493
TI  - Beyond interstrand crosslinks repair: contribution of FANCD2 and other Fanconi
      Anemia proteins to the replication of DNA.
AB  - Biallelic mutations of FANCD2 and other components of the Fanconi Anemia (FA)
      pathway cause a disease characterized by bone marrow failure, cancer
      predisposition and a striking sensitivity to agents that induce crosslinks
      between the two complementary DNA strands (inter-strand crosslinks-ICL). Such
      genotoxins were used to characterize the contribution of the FA pathway to the
      genomic stability of cells, thus unravelling the biological relevance of ICL
      repair in the context of the disease. Notwithstanding this, whether the defect in
      ICL repair as the sole trigger for the multiple physiological alterations
      observed in FA patients is still under investigation. Remarkably, ICL-independent
      functions of FANCD2 and other components of the FA pathway were recently
      reported. FANCD2 contributes to the processing of very challenging double strand
      ends (DSEs: one ended Double Strand Breaks -DSBs- created during DNA
      replication). Other ICL-independent functions of FANCD2 include prevention of DNA
      breakage at stalled replication forks and facilitation of chromosome segregation
      at the end of M phase. The current understanding of replication-associated
      functions of FANCD2 and its relevance for the survival of genomically stable
      cells is herein discussed.

PMID- 29031494
TI  - NB 06: From a simple lysosomotropic aSMase inhibitor to tools for elucidating the
      role of lysosomes in signaling apoptosis and LPS-induced inflammation.
AB  - Ceramide generation is involved in signal transduction of cellular stress
      response, in particular during stress-induced apoptosis in response to stimuli
      such as minimally modified Low-density lipoproteins, TNFalpha and exogenous C6
      ceramide. In this paper we describe 48 diverse synthetic products and evaluate
      their lysosomotropic and acid sphingomyelinase inhibiting activities in
      macrophages. A stimuli-induced increase of C16-ceramide in macrophages can be
      almost completely suppressed by representative compound NB 06 providing an
      effective protection of macrophages against apoptosis. Compounds like NB 06 thus
      offer highly interesting fields of application besides prevention of apoptosis of
      macrophages in atherosclerotic plaques in vessel walls. Most importantly, they
      can be used for blocking pH-dependent lysosomal processes and enzymes in general
      as well as for analyzing lysosomal dependent cellular signaling. Modulation of
      gene expression of several prominent inflammatory messengers IL1B, IL6, IL23A,
      CCL4 and CCL20 further indicate potentially beneficial effects in the field of
      (systemic) infections involving bacterial endotoxins like LPS or infections with
      influenza A virus.

PMID- 29031495
TI  - Evidence of mechanism in the evaluation of streptomycin and thalidomide.
AB  - This paper considers what evidence is needed to establish the effectiveness and
      safety of a drug therapy. The claim that A cures D is a particular case of a
      causal claim in medicine. So the paper begins with a general analysis of the
      evidence for causal claims in medicine. Such evidence is divided into two types:
      statistical evidence and evidence of mechanism. These are further divided into
      observational and interventional, producing a 2x2 classification. It is shown
      that historically there have different assessments of the importance of these
      different types of evidence. Evidence-based medicine (EBM) puts forward the
      thesis that claims of the form 'A cures D without harming the patient' can be
      established using only randomized controlled trials or RCTs. This thesis of EBM
      is criticized by considering two historical examples: streptomycin and
      thalidomide. Generalizing from these, it is claimed that the effectiveness and
      safety of a drug therapy can only be established by using both statistical
      evidence and evidence of mechanism. This is a specific instance of the Russo
      Williamson thesis.

PMID- 29031496
TI  - Ischemic Stroke in a Patient with Parry-Romberg Syndrome.
AB  - OBJECTIVE: This study aimed to discuss a case of a patient with a known diagnosis
      of Parry-Romberg syndrome (PRS) presenting with ischemic stroke, the second such
      reported case. BACKGROUND: PRS is a rare genetic disorder with progressive
      hemifacial atrophy, which usually presents within the first 2 decades of life.
      Neurologic manifestations include trigeminal neuralgia with associated deafness,
      hemifacial pain with associated migraine headaches, seizures, movement disorders,
      and neuropsychiatric symptoms. Many patients have elevated antinuclear antibody
      (ANA) titers. However, stroke is uncommon. CASE DESCRIPTION: A 34-year-old right
      handed woman, diagnosed with PRS at age 15, presented with right-sided weakness
      on waking up. Brain magnetic resonance imaging revealed a small infarct of the
      posterior limb of the left internal capsule. Vessel imaging revealed an aberrant
      right subclavian artery. Atrophy of the right-sided muscles of mastication is
      consistent with her known diagnosis of right-sided PRS. Stroke workup revealed a
      patent foramen ovale; however, no evidence of deep venous thrombosis was found.
      Hypercoagulability workup revealed an elevated ANA. The cause of stroke in this
      patient with PRS remains unclear, as she has no known risk factors. CONCLUSION:
      It is possible that elevated inflammatory markers associated with PRS may cause a
      proinflammatory state and predispose patients to small-vessel vasculopathy. It is
      important to note the association between PRS and ischemic stroke.

PMID- 29031497
TI  - Patent Foramen Ovale and the Risk of Cerebral Infarcts in Acute Pulmonary
      Embolism-A Prospective Observational Study.
AB  - BACKGROUND: Pulmonary embolism (PE) is associated with a risk of consecutive
      paradoxical embolism with brain infarction through a patent foramen ovale (PFO).
      The aims of this study were to assess the rate of new ischemic brain lesions
      (IBLs) using magnetic resonance imaging (MRI) during a 12-month follow-up period
      with anticoagulation and to evaluate the potential relationship with the presence
      of PFO on transesophageal echocardiography (TEE). SUBJECTS AND METHODS: Seventy
      eight patients with acute PE underwent baseline contrast TEE with brain MRI.
      After the 12-month follow-up, 58 underwent brain MRI. The rates of MRI
      documenting new IBLs were measured based on the presence of PFO. RESULTS: PFO was
      detected in 31 patients (39.7%). At baseline MRI, IBL was present in 39 of 78
      patients (50%). The presence of IBL was not significantly higher in patients with
      PFO than in patients without PFO (20 [64.5% patients with PFO] versus 19 [40.4%
      without PFO] of 39 patients with baseline IBL, P = .063). At the follow-up MRI,
      in the group with new IBL (9 of 58 patients, 15.5%), the number of patients with
      PFO was significantly higher than that without PFO (7 [33.3%] versus 2 [5.4%], P
      = .008). PFO was identified as an independent predictor of new IBL (odds ratio
      4.6 [1.6-47.4], P = .008). CONCLUSIONS: The presence of PFO was associated with
      new IBL in patients with PE. These patients are at a higher risk of ischemic
      stroke despite effective anticoagulation therapy.

PMID- 29031498
TI  - Low Free Triiodothyronine at Admission Predicts Poststroke Infection.
AB  - BACKGROUND: Poststroke infection (PSI) is common and is usually associated with a
      severe prognosis. We investigated the association between PSI and thyroid
      hormones, which are critical to immune regulation, in patients with acute stroke.
      METHODS: We retrospectively enrolled 520 consecutive patients with acute ischemic
      stroke (326 men; age, 71.9 +/- 13.2 years) admitted to our department between
      September 2014 and June 2016. The impact of serum thyroid hormone levels measured
      at admission (thyroid-stimulating hormone [TSH], free triiodothyronine [FT3], and
      free thyroxine [FT4]) on the PSI was evaluated using multivariate logistic
      regression analysis. RESULTS: We diagnosed 107 patients (20.6%; pneumonia, 65;
      urinary tract infection, 19; others, 23) with PSIs. While age (P <.001), body
      mass index (P = .0012), preadmission modified Rankin scale score (P = .0001),
      National Institutes of Health Stroke Scale score on admission (P <.001),
      admission FT3 level (P <.001), atrial fibrillation (P <.001), and ischemic heart
      disease (P = .0451) were significantly associated with PSI, we found no
      relationship among TSH levels, FT4 levels, and PSI occurrence. After multivariate
      adjustment, patients with PSIs were more frequently in the Q1 quartile (<=2.25
      pg/mL) than in the Q2 (2.26-2.55 pg/mL; P = .0251), Q3 (2.56-2.89 pg/mL; P =
      .0007), or Q4 (>=2.90 pg/mL; P = .0010) quartiles of FT3 levels. Moreover, low
      FT3 levels (<2.29 pg/mL) were independently associated with PSI occurrence (P =
      .0013). CONCLUSIONS: Low FT3 levels at admission are independently associated
      with PSI occurrence.

PMID- 29031499
TI  - MicroRNAs 15A and 16-1 Activate Signaling Pathways That Mediate Chemotaxis of
      Immune Regulatory B cells to Colorectal Tumors.
AB  - BACKGROUND & AIMS: B cells infiltrate tumors, but little is known about how they
      affect tumor growth and progression. microRNA15A (MIR15A or miRNA15A) and
      microRNA16-1 (MIR16-1 or miRNA16-1) regulate cell proliferation, apoptosis, and
      drug resistance. We investigated their involvement in B-cell-mediated immune
      suppression by colorectal tumors. METHODS: Mice with disruptions of the gene
      cluster that encodes MIR15A and MIR16-1 (knockout mice), and control (C57BL/B6)
      mice were given azoxymethane with dextran sodium sulfate (AD) to induce formation
      of colorectal tumors. Mice were given anti-CD20 to delete B cells, or injections
      of agomir to increase MIR15A and MIR16-1. Proliferation of CD8+T cells was
      measured by carboxyfluorescein-succinimidyl-ester analysis. Colon tissues were
      collected from mice and analyzed by flow cytometry, microRNA (miRNA) sequencing,
      and for cytokine production. Intestinal epithelial cells (IECs) were isolated and
      transfected with miRNA mimics, to identify their targets. We analyzed miRNA
      expression patterns and quantified B cells in colorectal cancer tissue
      microarrays derived from 90 patients who underwent surgical resection, from July
      2006 through April 2008, in Shanghai, China; expression data were compared with
      clinical outcomes. RESULTS: Tumors that developed in knockout mice following
      administration of AD were larger and contained greater numbers of B cells than
      tumors that grew in control mice. Most of the B cells in the tumors were positive
      for immunoglobulin A (IgA+). IgA+ B cells expressed high levels of immune
      regulatory molecules (programmed death ligand 1, interleukin 10, and transforming
      growth factor beta), and repressed the proliferation and activation of CD8+ T
      cells. Levels of MIR15A and MIR16-1 were reduced in colon tumors from mice,
      compared with nontumor colon tissue. Incubation of IECs with IL17A reduced
      expression of MIR15A and MIR16-1. Transgenic expression of MIR15A and MIR16-1 in
      IECs decreased activation of NF-kappaB and STAT1 by reducing expression of I
      kappaB kinases; this resulted in reduced production of chemokine (C-X-C motif)
      ligands 9 and 10 and decreased chemotaxis of IgA+ B cells. Tumors in mice
      injected with AD and agomir grew more slowly than tumors in mice not given in
      agomir and contained fewer IgA+ B cells. We found a negative correlation between
      levels of MIR15A and MIR16-1 and numbers of IgA+B cells in human colorectal tumor
      tissues; high levels of MIR15A and MIR16-1 and low numbers of IgA+B cells were
      associated with longer survival times of patients. CONCLUSIONS: We found
      increased levels of MIR15A and MIR16-1 to reduce numbers of IgA+ B cells in
      colorectal tumor tissues and correlate with increased survival time of patients.
      In mice that lack MIR15A and MIR16-1, colon tumors grow more rapidly and contain
      increased numbers of IgA+ B cells. MIR15A and MIR16-1 appear to activate
      signaling pathways required for B-cell-mediated immune suppression.

PMID- 29031500
TI  - Transcription and Signaling Regulators in Developing Neuronal Subtypes of Mouse
      and Human Enteric Nervous System.
AB  - BACKGROUND & AIMS: The enteric nervous system (ENS) regulates gastrointestinal
      function via different subtypes of neurons, organized into fine-tuned neural
      circuits. It is not clear how cell diversity is created within the embryonic ENS;
      information required for development of cell-based therapies and models of
      enteric neuropathies. We aimed to identify proteins that regulate ENS
      differentiation and network formation. METHODS: We generated and compared RNA
      expression profiles of the entire ENS, ENS progenitor cells, and non-ENS gut
      cells of mice, collected at embryonic days 11.5 and 15.5, when different subtypes
      of neurons are formed. Gastrointestinal tissues from R26ReYFP reporter mice
      crossed to Sox10-CreERT2 or Wnt1-Cre mice were dissected and the 6 populations of
      cells were isolated by flow cytometry. We used histochemistry to map
      differentially expressed proteins in mouse and human gut tissues at different
      stages of development, in different regions. We examined enteric neuronal
      diversity and gastric function in Wnt1-Cre x Sox6fl/fl mice, which do not express
      the Sox6 gene in the ENS. RESULTS: We identified 147 transcription and signaling
      factors that varied in spatial and temporal expression during development of the
      mouse ENS. Of the factors also analyzed in human ENS, most were conserved. We
      uncovered 16 signaling pathways (such as fibroblast growth factor and Eph/ephrin
      pathways). Transcription factors were grouped according to their specific
      expression in enteric progenitor cells (such as MEF2C), enteric neurons (such as
      SOX4), or neuron subpopulations (such as SATB1 and SOX6). Lack of SOX6 in the ENS
      reduced the numbers of gastric dopamine neurons and delayed gastric emptying.
      CONCLUSIONS: Using transcriptome and histochemical analyses of the developing
      mouse and human ENS, we mapped expression patterns of transcription and signaling
      factors. Further studies of these candidate determinants might elucidate the
      mechanisms by which enteric stem cells differentiate into neuronal subtypes and
      form distinct connectivity patterns during ENS development. We found expression
      of SOX6 to be required for development of gastric dopamine neurons.

PMID- 29031501
TI  - DNA Methylation and Transcription Patterns in Intestinal Epithelial Cells From
      Pediatric Patients With Inflammatory Bowel Diseases Differentiate Disease
      Subtypes and Associate With Outcome.
AB  - BACKGROUND & AIMS: We analyzed DNA methylation patterns and transcriptomes of
      primary intestinal epithelial cells (IEC) of children newly diagnosed with
      inflammatory bowel diseases (IBD) to learn more about pathogenesis. METHODS: We
      obtained mucosal biopsies (N = 236) collected from terminal ileum and ascending
      and sigmoid colons of children (median age 13 years) newly diagnosed with IBD (43
      with Crohn's disease [CD], 23 with ulcerative colitis [UC]), and 30 children
      without IBD (controls). Patients were recruited and managed at a hospital in the
      United Kingdom from 2013 through 2016. We also obtained biopsies collected at
      later stages from a subset of patients. IECs were purified and analyzed for
      genome-wide DNA methylation patterns and gene expression profiles. Adjacent
      microbiota were isolated from biopsies and analyzed by 16S gene sequencing. We
      generated intestinal organoid cultures from a subset of samples and genome-wide
      DNA methylation analysis was performed. RESULTS: We found gut segment-specific
      differences in DNA methylation and transcription profiles of IECs from children
      with IBD vs controls; some were independent of mucosal inflammation. Changes in
      gut microbiota between IBD and control groups were not as large and were
      difficult to assess because of large amounts of intra-individual variation. Only
      IECs from patients with CD had changes in DNA methylation and transcription
      patterns in terminal ileum epithelium, compared with controls. Colon epithelium
      from patients with CD and from patients with ulcerative colitis had distinct
      changes in DNA methylation and transcription patterns, compared with controls. In
      IECs from patients with IBD, changes in DNA methylation, compared with controls,
      were stable over time and were partially retained in ex-vivo organoid cultures.
      Statistical analyses of epithelial cell profiles allowed us to distinguish
      children with CD or UC from controls; profiles correlated with disease outcome
      parameters, such as the requirement for treatment with biologic agents.
      CONCLUSIONS: We identified specific changes in DNA methylation and transcriptome
      patterns in IECs from pediatric patients with IBD compared with controls. These
      data indicate that IECs undergo changes during IBD development and could be
      involved in pathogenesis. Further analyses of primary IECs from patients with IBD
      could improve our understanding of the large variations in disease progression
      and outcomes.

PMID- 29031502
TI  - Low Rates of Gastrointestinal and Non-Gastrointestinal Complications for
      Screening or Surveillance Colonoscopies in a Population-Based Study.
AB  - BACKGROUND: The full spectrum of serious non-gastrointestinal post-colonoscopy
      complications has not been well characterized. We analyzed rates of and factors
      associated with adverse post-colonoscopy gastrointestinal (GI) and non
      gastrointestinal events (cardiovascular, pulmonary, or infectious) attributable
      to screening or surveillance colonoscopy (S-colo) and non-screening or non
      surveillance colonoscopy (NS-colo). METHODS: We performed a population-based
      study of colonoscopy complications using databases from California hospital-owned
      and nonhospital-owned ambulatory facilities, emergency departments, and hospitals
      from January 1, 2005 through December 31, 2011. We identified patients who
      underwent S-colo (1.58 million), NS-colo (1.22 million), or low-risk comparator
      procedures (joint injection, aspiration, lithotripsy; arthroscopy, carpal tunnel;
      or cataract; 2.02 million) in California's Ambulatory Services Databases. We
      identified patients who developed adverse events within 30 days, and factors
      associated with these events, through patient-level linkage to California's
      Emergency Department and Inpatient Databases. RESULTS: After S-colo, the numbers
      of lower GI bleeding, perforation, myocardial infarction, and ischemic stroke per
      10,000-persons were 5.3 (95% confidence interval [CI], 4.8-5.9), 2.9 (95% CI, 2.5
      3.3), 2.5 (95% CI, 2.1-2.9), and 4.7 (95% CI, 4.1-5.2) without biopsy or
      intervention; with biopsy or intervention, numbers per 10,000-persons were 36.4
      (95% CI, 35.1-37.6), 6.3 (95% CI, 5.8-6.8), 4.2 (95% CI, 3.8-4.7), and 9.1 (95%
      CI, 8.5-9.7). Rates of dysrhythmia were higher. After NS-colo, event rates were
      substantially higher. Most serious complications led to hospitalization, and most
      GI complications occurred within 14 days of colonoscopy. Ranges of adjusted odds
      ratios for serious GI complications, myocardial infarction, ischemic stroke, and
      serious pulmonary events after S-colo vs comparator procedures were 2.18 (95% CI,
      2.02-2.36) to 5.13 (95% CI, 4.81-5.47), 0.67 (95% CI, 0.56-0.81) to 0.99 (95% CI,
      0.83-1.19), 0.66 (95% CI, 0.59-0.75) to 1.13 (95% CI, 0.99-1.29), and 0.64 (95%
      CI, 0.61-0.68) to 1.05 (95% CI, 0.98-1.11). Biopsy or intervention, comorbidity,
      black race, low income, public insurance, and NS-colo were associated with post
      colonoscopy adverse events. CONCLUSIONS: In a population-based study in
      California, we found that following S-colo, rates of serious GI adverse events
      were low but clinically relevant, and that rates of myocardial infarction,
      stroke, and serious pulmonary events were no higher than after low-risk
      comparator procedures. Rates of myocardial infarction are similar to, but rates
      of stroke are higher than, those reported for the general population.

PMID- 29031503
TI  - Assessing dentists' human papillomavirus-related health literacy for
      oropharyngeal cancer prevention.
AB  - BACKGROUND: Oropharyngeal cancers related to human papillomavirus (HPV) are on
      the rise. Dentists may be the next group of providers participating in the
      prevention of HPV. The aim of this study was to assess dentists' health literacy
      regarding the connection of HPV and oropharyngeal cancer. METHODS: The authors
      conducted 4 focus groups with dentists (N = 33) during a regional dental
      conference in 2016. Guided by the health literacy competencies (that is, access,
      understand, appraise, and apply), the authors used constant comparison methods
      for data analysis. RESULTS: Dentists mentioned a variety of informational sources
      (for example, dental journals and colleagues). Knowledge about the link between
      HPV and oropharyngeal cancer varied among participants. Participants appraised
      multiple patient and practice factors when deciding to have the discussion with
      patients. Some dentists discussed the HPV and oropharyngeal cancer connection
      with patients, and most conducted secondary screenings. CONCLUSIONS: Findings
      indicate areas for intervention, including creating awareness of trusted
      informational sources, as well as increasing HPV knowledge and understanding the
      multiple patient (for example, age) and practice (for example, open operatories)
      appraisal factors. Moreover, enhancing the communication skills of dentists with
      patients is needed to improve HPV-related cancer prevention education. PRACTICAL
      IMPLICATIONS: Addressing dentists' HPV-related health literacy has the potential
      to improve dentists' HPV-related prevention practices, including expanding
      patient education about this topic and increasing HPV vaccination knowledge,
      ultimately contributing to the reduction of oropharyngeal cancers.

PMID- 29031504
TI  - [Therapeutic targeting of Notch signaling in cancer].
AB  - The Notch pathway plays an essential role during embryonal development and tissue
      in adults. Notch signaling occurs through transmembrane receptors which undergo
      several proteolytic cleavages that lead to the release of the Notch
      intracytoplasmic domain (NICD), which in turn activates the transcription of
      target genes. Oncogenic alterations of Notch receptors were first identified in T
      acute lymphoblastic leukemia and subsequently in solid tumors and other
      hematological malignancies. The important role of Notch signaling in cancer makes
      it an interesting target for drug development. Several classes of compounds
      targeting Notch signaling are currently in clinical development. However, the
      complexity of Notch signaling as well as its importance in tissue homeostasis
      makes the clinical development of these therapies more complex than anticipated.
      Additional clinical and preclinical investigations are needed to adequately
      target Notch signaling in cancer therapy.

PMID- 29031505
TI  - [Histological and molecular classification of endometrial carcinoma and
      therapeutical implications].
AB  - Endometrial cancer is the fourth cause of cancer in women in France and is the
      second most common cancer of the gynecologic cancer after breast cancer with 7275
      new cases in 2012. The incidence of this neoplasm tends to increase with
      population aging, diabetes and obesity's augmentation. In rare cases, a
      hereditary factor has been described: Lynch's syndrome. The therapeutic
      management of the patient depends on the endometrial biopsy which specifies the
      histological type and the histo-prognostic grade as well as the MRI which allow
      the tumor staging. Within the last decade, improvement in technologies such as
      genomic, transcriptomic and histological analyses, allowed the establishment of
      new and finer classifications of endometrial carcinomas. The latest
      classification proposed by The Cancer Genomic Atlas (TCGA), has been made
      routinely applicable through the international consortium TransPORTEC. It
      consists of 4 groups listed from good to poor prognosis: (1) ultra-mutated
      "POLE"; (2) hyper-mutated "MSI"; (3) low copy number "NSMP" and (4) high number
      of copies "TP53 mutated" (serous-like). This integrated characterization combined
      with mutational data opens new opportunities for therapeutic strategies.

PMID- 29031506
TI  - [Cyto-histological correlation in the management of parotid gland tumors: A
      retrospective study of 160 cases].
AB  - INTRODUCTION: The aim of this study was to correlate the cytological and
      histological results and evaluate the diagnostic performance of fine-needle
      aspiration cytology (FNAC) in the management of parotid gland tumors. METHODS:
      This retrospective study included 160 patients with a parotid gland tumor who
      underwent fine-needle aspiration and parotidectomy surgery between January 2005
      and August 2016 at the Limoges university hospital center. RESULTS: On 160 fine
      needle aspirations performed, fine-needle aspiration diagnoses were: 77 benign
      lesions, 35 malignant lesions and 48 non-diagnostic cases. Final histological
      diagnosis revealed there were 113 benign lesions and 47 malignant lesions. A
      hundred and one cytological diagnoses were accurate over 112 contributive fine
      needle aspirations: seven false-negative cases and 4 false-positive cases were
      observed. The sensitivity, specificity, and accuracy were 82, 95 and 90%
      respectively for fine-needle aspiration, and 83, 95 and 92% respectively for
      association of fine-needle aspiration and magnetic resonance imaging. Diagnostic
      concordance between fine-needle aspiration and final histology for malignant
      lesions was 78%. A greater number of contributive fine-needle aspirations was
      observed among experimented operators. DISCUSSION: Fine-needle aspiration is a
      reliable, safe and effective diagnostic tool that allows good differentiation
      between malignant and benign diagnosis in the preoperative management of parotid
      gland tumors. The association of fine-needle aspiration and magnetic resonance
      imaging (MRI) can improve diagnostic performance.

PMID- 29031507
TI  - [Sport coaching for psychological and social recovery after hematological cancer:
      An innovative perspective].
AB  - This study is a first step towards the transfer of knowledge and practices
      between psychological support and performance in elite sport and a patient's
      "social recovery" in oncology. This proposal brings together people engaged in a
      variety of healthcare and relationship support roles, and aims to set up a
      support system beyond the hospital context. It questions the ability of elite
      sport management and its main actors, the "Great Coaches", to contribute to the
      support of patients in cancer remission through an onco-coaching approach. This
      innovative proposal is initiated by a life coaching pilot study designed for
      hematologic cancer patients in remission after a hematopoietic stem cell
      transplantation.

PMID- 29031508
TI  - Specialist nurses' experiences when caring for preverbal children in pain in the
      prehospital context in Sweden.

PMID- 29031510
TI  - Pain and consciousness.
AB  - The aversive experience we call "pain" results from the coordinated activation of
      multiple brain areas, commonly described as a "pain matrix". This is not a fixed
      arrangement of structures but rather a fluid system composed of several
      interacting networks: A 'nociceptive matrix' includes regions receiving input
      from ascending nociceptive systems, and ensures the bodily characteristics of
      physical pain. A further set of structures receiving secondary input supports the
      'salience' attributes of noxious stimuli, triggers top-down cognitive controls,
      and -most importantly- ensures the passage from pre-conscious nociception to
      conscious pain. Expectations and beliefs can still modulate the conscious
      experience via activity in supramodal regions with widespread cortical
      projections such as the ventral tegmental area. Intracortical EEG responses in
      humans show that nociceptive cortical processing is initiated in parallel in
      sensory, motor and limbic areas; it progresses rapidly to the recruitment of
      anterior insular and fronto-parietal networks, and finally to the activation of
      perigenual, posterior cingulate and hippocampal structures. Functional
      connectivity between sensory and high-level networks increases during the first
      second post-stimulus, which may be determinant for access to consciousness. A
      model is described, progressing from unconscious sensori-motor and limbic
      processing of spinothalamic and spino-parabrachial input, to an immediate sense
      of awareness supported by coordinated activity in sensorimotor and fronto-parieto
      insular networks, and leading to full declarative consciousness through
      integration with autobiographical memories and self-awareness, involving
      posterior cingulate and medial temporal areas. This complete sequence is only
      present during full vigilance states. We contend, however, that even in
      unconscious subjects, repeated limbic and vegetative activation by painful
      stimuli via spino-amygdalar pathways can generate implicit memory traces and
      stimulus-response abnormal sequences, possibly contributing to long-standing
      anxiety or hyperalgesic syndromes in patients surviving coma.

PMID- 29031509
TI  - Mining Filarial Genomes for Diagnostic and Therapeutic Targets.
AB  - Filarial infections of humans cause some of the most important neglected tropical
      diseases. The global efforts for eliminating filarial infections by mass drug
      administration programs may require additional tools (safe macrofilaricidal
      drugs, vaccines, and diagnostic biomarkers). The accurate and sensitive detection
      of viable parasites is essential for diagnosis and for surveillance programs.
      Current community-wide treatment modalities do not kill the adult filarial worms
      effectively; hence, there is a need to identify and develop safe macrofilaricidal
      drugs. High-throughput sequencing, mass spectroscopy methods and advances in
      computational biology have greatly accelerated the discovery process. Here, we
      describe post-genomic developments toward the identification of diagnostic
      biomarkers and drug targets for the filarial infection of humans.

PMID- 29031511
TI  - The mechanical fingerprint of murine excisional wounds.
AB  - : A multiscale mechanics approach to the characterization of murine excisional
      wounds subjected to uniaxial tensile loading is presented. Local strain analysis
      at a physiological level of tension uncovers the presence of two distinct regions
      within the wound: i) a very compliant peripheral cushion and ii) a core area
      undergoing modest deformation. Microstructural visualizations of stretched wound
      specimens show negligible engagement of the collagen located in the center of a 7
      day old wound; fibers remain coiled despite the applied tension, confirming the
      existence of a mechanically isolated wound core. The compliant cushion located at
      the wound periphery appears to protect the newly-formed tissue from excessive
      deformation during the phase of new tissue formation. The early remodeling phase
      (day 14) is characterized by a restored mechanical connection between far field
      and wound center. The latter remains less deformable, a characteristic possibly
      required for cell activities during tissue remodeling. The distribution of
      fibrillary collagens at these two time points corresponds well to the identified
      heterogeneity of mechanical properties of the wound region. This novel approach
      provides new insight into the mechanical properties of wounded skin and will be
      applicable to the analysis of compound-treated wounds or wounds in genetically
      modified tissue. STATEMENT OF SIGNIFICANCE: Biophysical characterization of
      healing wounds is crucial to assess the recovery of the skin barrier function and
      the associated mechanobiological processes. For the first time, we performed
      highly resolved local deformation analysis to identify mechanical characteristics
      of the wound and its periphery. Our results reveal the presence of a compliant
      cushion surrounding a stiffer wound core; we refer to this heterogeneous
      mechanical behavior as "mechanical fingerprint" of the wound. The mechanical
      response is shown to progress towards that of the intact skin as healing takes
      place. Histology and multiphoton microscopy suggest that wounded skin recovers
      its mechanical function via progressive reconnection of the newly-deposited
      collagen fibers with the surrounding intact matrix.

PMID- 29031512
TI  - Current antiviral drugs and their analysis in biological materials - Part II:
      Antivirals against hepatitis and HIV viruses.
AB  - This review is a Part II of the series aiming to provide comprehensive overview
      of currently used antiviral drugs and to show modern approaches to their
      analysis. While in the Part I antivirals against herpes viruses and antivirals
      against respiratory viruses were addressed, this part concerns antivirals against
      hepatitis viruses (B and C) and human immunodeficiency virus (HIV). Many novel
      antivirals against hepatitis C virus (HCV) and HIV have been introduced into the
      clinical practice over the last decade. The recent broadening portfolio of these
      groups of antivirals is reflected in increasing number of developed analytical
      methods required to meet the needs of clinical terrain. Part II summarizes the
      mechanisms of action of antivirals against hepatitis B virus (HBV), HCV, and HIV,
      their use in clinical practice, and analytical methods for individual classes. It
      also provides expert opinion on state of art in the field of bioanalysis of these
      drugs. Analytical methods reflect novelty of these chemical structures and use by
      far the most current approaches, such as simple and high-throughput sample
      preparation and fast separation, often by means of UHPLC-MS/MS. Proper method
      validation based on requirements of bioanalytical guidelines is an inherent part
      of the developed methods.

PMID- 29031513
TI  - Effective cues for accelerating young drivers' time to transfer control following
      a period of conditional automation.
AB  - OBJECTIVE: During conditional automated driving, a transition from the automated
      driving suite to manual control requires the driver to take over control at a
      moment's notice. Thus, it is critical that a driver be made situationally aware
      as quickly as possible in those conditions where he or she may not be paying full
      attention. Recent research suggests that specific cues about upcoming hazards
      (e.g., "crosswalk ahead") can increase the drivers' situation awareness during
      these safety-critical take-over situations when compared with a general cue
      ("take over control"). The current study examines whether this increased
      situation awareness which occurs as a result of more specific cues translates
      into improved hazard mitigation performance within the same limited time window.
      METHOD: Fifty-seven drivers were randomly assigned to one of five between
      subjects conditions (one control condition and four experimental auditory cue
      conditions) that varied in the specificity of information provided about an
      upcoming hazard. The four experimental conditions included a period of
      conditional automated driving where the driver was engaged in a driving
      irrelevant task and looked away from the forward roadway prior to a take-over
      request. Drivers in the fifth condition had no cue and drove manually throughout.
      The same six simulator scenarios were used in all five conditions to evaluate how
      well the driver mitigated a hazard. The average velocity, standard deviation of
      velocity, and average absolute acceleration were recorded along with the glance
      behaviors of drivers. RESULTS: In general, during the 4s prior to a latent hazard
      (following the alerting cues in the automated driving conditions), the more
      likely a driver was to glance towards a latent hazard, the more likely the driver
      was to reduce his or her speed. Moreover, analyses focusing solely on hazard
      mitigation behavior revealed patterns that mirrored the glance behavior results.
      Specifically, drivers that were presented with cues that described the
      environments in which hazards were likely to occur were more likely to
      demonstrate vehicle behaviors that were consistent with speed reductions (lower
      velocity, higher speed variability, and higher absolute acceleration) than were
      drivers who were presented general cues or cues about the identity of the
      upcoming hazards. CONCLUSION: Even in as little as 4s prior to a potential
      hazard, cues that inform the driver of the environment in which the hazard is
      likely to occur increase the likelihood that the driver mitigates the crash
      compared with drivers who are provided general information or threat identity
      information.

PMID- 29031514
TI  - Erratum.

PMID- 29031516
TI  - Growth of adult spinal cord in knifefish: Development and parametrization of a
      distributed model.
AB  - The study of indeterminate-growing organisms such as teleost fish presents a
      unique opportunity for improving our understanding of central nervous tissue
      growth during adulthood. Integrating the existing experimental data associated
      with this process into a theoretical framework through mathematical or
      computational modeling provides further research avenues through sensitivity
      analysis and optimization. While this type of approach has been used extensively
      in investigations of tumor growth, wound healing, and bone regeneration, the
      development of nervous tissue has been rarely studied within a modeling
      framework. To address this gap, the present work introduces a distributed model
      of spinal cord growth in the knifefish Apteronotus leptorhynchus, an established
      teleostean model of adult growth in the central nervous system. The proposed
      model incorporates two mechanisms, cell proliferation by active stem/progenitor
      cells and cell drift due to population pressure, both of which are subject to
      global constraints. A coupled reaction-diffusion equation approach was adopted to
      represent the densities of actively-proliferating and non-proliferating cells
      along the longitudinal axis of the spinal cord. Computer simulations using this
      model yielded biologically-feasible growth trajectories. Subsequent comparisons
      with whole-organism growth curves allowed the estimation of previously-unknown
      parameters, such as relative growth rates.

PMID- 29031515
TI  - Association of Antidementia Drugs and Mortality in Community-Dwelling Frail Older
      Patients With Dementia: The Role of Mortality Risk Assessment.
AB  - OBJECTIVE: To evaluate whether treatment with antidementia drugs is associated
      with reduced mortality in older patients with different mortality risk at
      baseline. DESIGN: Retrospective. SETTING: Community-dwelling. PARTICIPANTS: A
      total of 6818 older people who underwent a Standardized Multidimensional
      Assessment Schedule for Adults and Aged Persons (SVaMA) evaluation to determine
      accessibility to homecare services or nursing home admission from 2005 to 2013 in
      the Padova Health District, Italy were included. MEASUREMENTS: Mortality risk at
      baseline was calculated by the Multidimensional Prognostic Index (MPI), based on
      information collected with the SVaMA. Participants were categorized to have mild
      (MPI-SVaMA-1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) mortality risk.
      Propensity score-adjusted hazard ratios (HR) of 2-year mortality were calculated
      according to antidementia drug treatment. RESULTS: Patients treated with
      antidementia drugs had a significant lower risk of death than untreated patients
      (HR 0.82; 95% confidence interval [CI] 0.73-0.92 and 0.56; 95% CI 0.49-0.65 for
      patients treated less than 2 years and more than 2 years treatment,
      respectively). After dividing patients according to their MPI-SVaMA grade,
      antidementia treatment was significantly associated with reduced mortality in the
      MPI-SVaMA-1 mild (HR 0.71; 95% CI 0.54-0.92) and MPI-SVaMA-2 moderate risk (HR
      0.61; 95% CI 0.40-0.91, matched sample), but not in the MPI-SVaMA-3 high risk of
      death. CONCLUSIONS: This large community-dwelling patient study suggests that
      antidementia drugs might contribute to increased survival in older adults with
      dementia with lower mortality risk.

PMID- 29031517
TI  - Promotion of cooperation in evolutionary game dynamics with local information.
AB  - In this paper, we propose a strategy-updating rule driven by local information,
      which is called Local process. Unlike the standard Moran process, the Local
      process does not require global information about the strategic environment. By
      analyzing the dynamical behavior of the system, we explore how the local
      information influences the fixation of cooperation in two-player evolutionary
      games. Under weak selection, the decreasing local information leads to an
      increase of the fixation probability when natural selection does not favor
      cooperation replacing defection. In the limit of sufficiently large selection,
      the analytical results indicate that the fixation probability increases with the
      decrease of the local information, irrespective of the evolutionary games.
      Furthermore, for the dominance of defection games under weak selection and for
      coexistence games, the decreasing of local information will lead to a speedup of
      a single cooperator taking over the population. Overall, to some extent, the
      local information is conducive to promoting the cooperation.

PMID- 29031518
TI  - Investigation of nonlinear epidemiological models for analyzing and controlling
      the MERS outbreak in Korea.
AB  - Much concern has arisen regarding serious epidemics due to the Middle East
      Respiratory Syndrome (MERS) coronavirus. The first MERS case of Korea was
      reported on 20 May 2015, and since then, the MERS outbreak in Korea has resulted
      in hundreds of confirmed cases and tens of deaths. Deadly infectious diseases
      such as MERS have significant direct and indirect social impacts, which include
      disease-induced mortality and economic losses. Also, a delayed response to the
      outbreak and underestimating its danger can further aggravate the situation.
      Hence, an analysis and establishing efficient strategies for preventing the
      propagation of MERS is a very important and urgent issue. In this paper, we
      propose a class of nonlinear susceptible-infectious-quarantined (SIQ) models for
      analyzing and controlling the MERS outbreak in Korea. For the SIQ based ordinary
      differential equation (ODE) model, we perform the task of parameter estimation,
      and apply optimal control theory to the controlled SIQ model, with the goal of
      minimizing the infectious compartment population and the cost of implementing the
      quarantine and isolation strategies. Simulation results show that the proposed
      SIQ model can explain the observed data for the confirmed cases and the
      quarantined cases in the MERS outbreak very well, and the number of the MERS
      cases can be controlled reasonably well via the optimal control approach.

PMID- 29031519
TI  - Every successful journal relies on its reviewers.

PMID- 29031520
TI  - Executive function: Responses to aerobic exercise in Alzheimer's disease.
AB  - Executive dysfunction occurs early and is prevalent in Alzheimer's disease (AD).
      This study tested the ability of different measures for identifying changes in
      executive function and the effect of 6-months of aerobic exercise on executive
      function in older adults with mild to moderate AD, using a single-group, repeated
      measures design (n = 28, age 78.1 +/- 8.37). Factor analysis and linear mixed
      effects model analyses showed that individually the Exit Interview-25 (EXIT-25),
      Behavioral Dyscontrol Scale (BDS), and Golden Stroop test were the preferred
      instruments for measuring changes in executive function in the sample. The COWAT
      and TMT had substantial floor effects limiting their ability to identify changes
      in executive function. A single latent factor was sufficient to describe the
      heterogeneity of executive function. Over 6 months, aerobic exercise maintained
      executive function (effect size = -0.11, -0.24, -0.27, and -0.21 for the EXIT-25,
      BDS, Stroop, and latent factor, respectively). Decline in the latent factor
      (effect size = -0.21, p = 0.06) was minimal and comparable to that in global
      cognition (effect size = -0.20, p = 0.34). Aerobic exercise may be effective on
      maintaining executive function in AD.

PMID- 29031521
TI  - Surgical Thoracic Transplant Training: Super Fellowship-Is It Super?
AB  - OBJECTIVE: The quality of training provided to thoracic transplant fellows is a
      critical step in the care of complex patients undergoing transplant. The training
      varies since it is not an accreditation council for graduate medical education
      accredited fellowship. METHOD: A total of 104 heart or lung transplant program
      directors throughout the United States were sent a survey of 24 questions
      focusing on key aspects of training, fellowship training content and thoracic
      transplant job satisfaction. Out of the 104 programs surveyed 45 surveys (43%)
      were returned. RESULTS: In total, 26 programs offering a transplant fellowship
      were included in the survey. Among these programs 69% currently have fellows of
      which 56% are American Board of Thoracic Surgery board eligible. According to the
      United Network for Organ Sharing (UNOS) requirements, 46% of the programs do not
      meet the requirements to be qualified as a primary heart transplant surgeon. A
      total of 23% of lung transplant programs also perform less than the UNOS minimum
      requirements. Only 24% have extra-surgical curriculum. Out of the participating
      programs, only 38% of fellows secured a job in a hospital setting for performing
      transplants. An astounding 77% of replies site an unpredictable work schedule as
      the main reason that makes thoracic transplant a less than favorable profession
      among new graduates. Long hours were also a complaint of 69% of graduates who
      agreed that their personal life is affected by excessive work hours. CONCLUSION:
      Annually, almost half of all thoracic transplant programs perform fewer than the
      UNOS requirements to be a primary thoracic surgeon. This results in a majority of
      transplant fellows not finding a suitable transplant career. The current and
      future needs for highly qualified thoracic transplant surgeons will not be met
      through our existing training mechanisms.

PMID- 29031522
TI  - Video-Based Surgical Learning: Improving Trainee Education and Preparation for
      Surgery.
AB  - BACKGROUND: Since the end of the XIX century, teaching of surgery has remained
      practically unaltered until now. With the dawn of video-assisted laparoscopy,
      surgery has faced new technical and learning challenges. Due to technological
      advances, from Internet access to portable electronic devices, the use of online
      resources is part of the educational armamentarium. In this respect, videos have
      already proven to be effective and useful, however the best way to benefit from
      these tools is still not clearly defined. AIMS: To assess the importance of video
      based learning, using an electronic questionnaire applied to residents and
      specialists of different surgical fields. METHODS: Importance of video-based
      learning was assessed in a sample of 141 subjects, using a questionnaire
      distributed by a GoogleDoc online form. RESULTS: We found that 98.6% of the
      respondents have already used videos to prepare for surgery. When comparing video
      sources by formation status, residents were found to use Youtube significantly
      more often than specialists (p < 0.001). Additionally, residents placed more
      value on didactic illustrations and procedure narration than specialists (p <
      0.001). On the other hand, specialists prized surgeon's technical skill and the
      presence of tips and tricks much more than residents (p < 0.001). CONCLUSION:
      Video-based learning is currently a hallmark of surgical preparation among
      residents and specialists working in Portugal. Based on these findings we believe
      that the creation of quality and scientifically accurate videos, and subsequent
      compilation in available video-libraries appears to be the future landscape for
      video-based learning.

PMID- 29031523
TI  - 6-Hydroxy-3-O-methyl-kaempferol 6-O-glucopyranoside potentiates the anti
      proliferative effect of interferon alpha/beta by promoting activation of the
      JAK/STAT signaling by inhibiting SOCS3 in hepatocellular carcinoma cells.
AB  - Suppressor of cytokine signaling 3 (SOCS3) is a key negative regulator of type I
      interferon (IFN alpha/beta) signaling. Inhibition of SOCS3 by small molecules may
      be a new strategy to enhance the efficacy of type I IFN and reduce its side
      effects. We established a cell-based screening assay using human hepatoma HepG2
      cells stably transfected with a plasmid wherein the luciferase reporter activity
      was propelled by interferon alpha-stimulated response element (ISRE), which is a
      motif specifically recognized by type I IFN-induced activation of Janus
      kinase/signal transducer and activator of transcription (JAK/STAT) pathway. After
      screening our chemical library, 6-hydroxy-3-O-methyl-kaempferol 6-O
      glucopyranoside (K6G) was identified to be a potent activator of type I IFN with
      EC50 value of 3.33+/-0.04MUM. K6G enhanced the phosphorylation of JAK1, Tyk2, and
      STAT1/2 but decreased the phosphorylation of STAT3. K6G also promoted endogenous
      IFN-alpha-regulated genes expression. More interestingly, K6G significantly
      decreased the expression of SOCS3 without affecting the expression of SOCS1.
      Furthermore, K6G enhanced the anti-proliferative effect of IFN-alpha on
      hepatocellular carcinoma (HCC) cells. These results suggested that K6G
      potentiated the inhibitory effect of IFN-alpha on HCC cell proliferation through
      activation of the JAK/STAT signaling pathway by inhibiting SOCS3 expression. K6G
      warrants further investigation as a novel therapeutic method to enhance the
      efficacy of IFN-alpha/beta.

PMID- 29031524
TI  - Analysis of pelvic strain in different gait configurations in a validated cohort
      of computed tomography based finite element models.
AB  - The pelvis functions to transmit upper body loads to the lower limbs and is
      critical in human locomotion. Semi-automated, landmark-based finite element (FE)
      morphing and mapping techniques eliminate the need for segmentation and have
      shown to accelerate the generation of multiple specimen-specific pelvic FE models
      to enable the study of pelvic mechanical behaviour. The purpose of this research
      was to produce an experimentally validated cohort of specimen-specific FE models
      of the human pelvis and to use this cohort to analyze pelvic strain patterns
      during gait. Using an initially segmented specimen-specific pelvic FE model asa
      source model, four more specimen-specific pelvic FE models were generated from
      target clinical CT scans using landmark-based morphing and mapping techniques. FE
      strains from the five models were compared to the experimental strains obtained
      from cadaveric testing via linear regression analysis, (R2 values ranging from
      0.70 to 0.93). Inter-specimen variability in FE strain distributions was seen
      among the five specimen-specific pelvic FE models. The validated cohort of
      specimen-specific pelvic FE models was utilized to examine pelvic strains at
      different phases of the gait cycle. Each validated specimen-specific FE model was
      reconfigured into gait cycle phases representing heel-strike/heel-off and
      midstance/midswing. No significant difference was found in the double-leg stance
      and heel-strike/heel-off models (p=0.40). A trend was observed between double-leg
      stance and midstance/midswing models (p=0.07), and a significant difference was
      found between heel-strike/heel-off models and midstance/midswing models (p=0.02).
      Significant differences were also found in comparing right vs. left models (heel
      strike/heel-off p=0.14, midstance/midswing p=0.04).

PMID- 29031525
TI  - Impact of CLSI and EUCAST Cefepime breakpoint changes on the susceptibility
      reporting for Enterobacteriaceae.
AB  - OBJECTIVE: We analyzed the effects of different cefepime MIC breakpoints on
      Enterobacteriaceae cefepime susceptibility and the presence of AmpC and extended
      spectrum beta-lactamase (ESBL) genes within the cefepime MIC interpretative
      categories. METHODS: Using Enterobacteriaceae susceptibility data from 2013
      comparisons of MIC breakpoints were performed using Pearson's chi-squared test.
      Molecular testing on a subset of isolates was done. RESULTS: Among 3784 non
      duplicate clinical isolates, cefepime susceptibility decreased from 97.6% to
      96.1% to 93.7% for CLSI 2013, CLSI 2014, and EUCAST 2011, respectively. In
      ceftriaxone non-susceptible isolates, cefepime susceptibility decreased from 79%
      to 66% (P<0.0001) using CLSI 2013 and 2014, respectively, which was greater and
      statistically significant for Escherichia coli and Klebsiella spp. but not for
      Enterobacter spp. (P=0.06). Isolates with MIC <=1MUg/mL more often harbored AmpC
      (77%) than ESBL (18%) genes. CONCLUSIONS: Lower cefepime MIC breakpoints decrease
      cefepime susceptibility for isolates harboring ESBLs, while sparing the majority
      of those with AmpCs.

PMID- 29031527
TI  - Erratum.

PMID- 29031526
TI  - The Temporal Artery Island Flap: A Good Reconstructive Option for Small to Medium
      Sized Facial Defects.
AB  - PURPOSE: The reconstruction of facial defects is esthetically vital because of
      the unique skin color and texture of the face. The aim of this study was to show
      the utility of different temporal artery island flap designs for the
      reconstruction of upper and middle facial defects without contrast to the color
      and texture of the face. MATERIALS AND METHODS: This study is a retrospective
      case series conducted from November 2004 through May 2015. Patients older than 18
      years with upper and middle facial defects smaller than 5 cm were included.
      RESULTS: The temporal artery island flap was used in 34 patients (21 men and 13
      women). The etiologies were skin tumor in 17 patients, trauma in 10 patients, and
      burns in 7 patients. Major defect localization was in the temporal area in 12
      patients, followed by the ear in 9 patients, the cheek in 6 patients, the eyebrow
      in 4 patients, and the nose in 3 patients. Flap designs consisted of the
      antegrade-flow island flap, the V-Y flap, and reverse-flow island flap in 23, 7,
      and 4 patients, respectively. All flaps survived completely except for 1 partial
      flap necrosis. Scars in the donor areas were inconspicuous. Patients' median age
      was 47.5 years (quartiles, 40.75 to 54), 61.8% were men, and median duration of
      follow-up was 11 months (range, 6 to 18 months). CONCLUSIONS: The temporal artery
      island flap could be a good option for the closure of minor to medium-size
      defects of the upper and middle face because of its good color and texture match,
      constant and reliable pedicle, wide pivotal movement, low donor site morbidity,
      and reverse-flow pattern.

PMID- 29031528
TI  - A Rare, Unusual Presentation of Primary Tuberculosis in the Temporomandibular
      Joint.
AB  - Tuberculosis (TB) is a very common health problem in developing nations such as
      India. It can present as its primary form or as secondary forms (extrapulmonary
      TB). Maxillofacial manifestations of TB compose nearly 10% of all extrapulmonary
      manifestations of the disease. Extrapulmonary TB involving the maxillofacial
      region is very rare and can present in any tissues in this region. These
      infections generally involve the head and neck through hematogenous or lymphatic
      routes. Very few cases of primary TB of the temporomandibular joint (TMJ) have
      been reported in the literature. The presentation of TB infection of the TMJ can
      resemble arthritis, osteomyelitis, or any other kind of chronic joint disease. It
      is very important to diagnose this disease at an early stage. If left untreated,
      it can prove fatal within 5 years in more than half the cases. Therefore, early
      diagnosis and management of these cases is critical. This article describes a
      case of primary TB of the TMJ that presented as a preauricular swelling.

PMID- 29031529
TI  - Enhanced Surgical Outcomes in Patients With Skeletal Class III Facial Asymmetry
      by 3-Dimensional Surgical Simulation.
AB  - PURPOSE: With the advance of image fusion techniques, the creation of 3
      dimensional (3D) virtual head and 3D surgical simulations has provided previews
      of surgical procedures. The aim of this study was to investigate the surgical
      outcomes in patients receiving orthognathic surgery (OGS) with the guidance of 3D
      computer-assisted surgical simulation. PATIENTS AND METHODS: The study included
      34 consecutive patients (15 men and 19 women; age, 18.1 to 33.0 yr) with skeletal
      Class III facial asymmetry who underwent bimaxillary OGS. One-week postoperative
      cone-beam computed tomographic craniofacial images (Ta) were constructed and
      superimposed on preoperative simulated virtual images (Ts) at the cranial base
      and surfaces of the frontal and periorbital regions. The 3D cephalometric
      landmarks were measured relative to 3 reference planes. The outcomes among
      different experience levels of surgeons also were compared. RESULTS: Although the
      mean values between Ta and Ts were small, statistical differences were observed
      in the center of maxillary and mandibular incisors and the B point relative to
      the midline and in the maxillary first molar in vertical distances, sagittal
      dentoskeletal dimensions, and pitch angles. The root mean square deviations
      (RMSDL) of measurement variables relative to center landmark accuracy were 1.5
      and less than 2 mm at the maxilla and mandible, respectively. RMSDL greater than
      2 mm was located at the maxillary first molar in the vertical distance and in the
      sagittal dimension at the anterior nasal spine and B point. Variables related to
      centering the midline structures were highly inter-related. The roll angle
      deviation was associated with centering the midline landmarks. The yaw angle
      deviation was not associated with midline correction. CONCLUSION: With guidance
      from 3D surgical simulation, surgeons could achieve similar outcomes to correct
      facial asymmetry regardless of their years of practice.

PMID- 29031530
TI  - Human torque is not present in chimpanzee brain.
AB  - We searched for positional brain surface asymmetries measured as displacements
      between corresponding vertex pairs in relation to a mid-sagittal plane in
      Magnetic Resonance (MR) images of the brains of 223 humans and 70 chimpanzees. In
      humans deviations from symmetry were observed: 1) a Torque pattern comprising
      right-frontal and left-occipital "petalia" together with downward and rightward
      "bending" of the occipital extremity, 2) leftward displacement of the anterior
      temporal lobe and the anterior and central segments of superior temporal sulcus
      (STS), and 3) posteriorly in the position of left occipito-temporal surface
      accompanied by a clockwise rotation of the left Sylvian Fissure around the left
      right axis. None of these asymmetries was detected in the chimpanzee, nor was
      associated with a sex difference. However, 4) an area of cortex with its long
      axis parallel to the olfactory tract in the orbital surface of the frontal lobe
      was found in humans to be located higher on the left in females and higher on the
      right in males. In addition whereas the two hemispheres of the chimpanzee brain
      are equal in extent in each of the three dimensions of space, in the human brain
      the left hemisphere is longer (p = 3.6e-12), and of less height (p = 1.9e-3), but
      equal in width compared to the right. Thus the asymmetries in the human brain are
      potential correlates of the evolution of the faculty of language.

PMID- 29031531
TI  - A functional connectivity-based neuromarker of sustained attention generalizes to
      predict recall in a reading task.
AB  - Sustaining attention to the task at hand is a crucial part of everyday life, from
      following a lecture at school to maintaining focus while driving. Lapses in
      sustained attention are frequent and often problematic, with conditions such as
      attention deficit hyperactivity disorder affecting millions of people worldwide.
      Recent work has had some success in finding signatures of sustained attention in
      whole-brain functional connectivity (FC) measures during basic tasks, but since
      FC can be dynamic and task-dependent, it remains unclear how fully these
      signatures would generalize to a more complex and naturalistic scenario. To this
      end, we used a previously defined whole-brain FC network - a marker of attention
      that was derived from a sustained attention task - to predict the ability of
      participants to recall material during a free-viewing reading task. Though the
      predictive network was trained on a different task and set of participants, the
      strength of FC in the sustained attention network predicted reading recall
      significantly better than permutation tests where behavior was scrambled to
      simulate chance performance. To test the generalization of the method used to
      derive the sustained attention network, we applied the same method to our reading
      task data to find a new FC network whose strength specifically predicts reading
      recall. Even though the sustained attention network provided significant
      prediction of recall, the reading network was more predictive of recall accuracy.
      The new reading network's spatial distribution indicates that reading recall is
      highest when temporal pole regions have higher FC with left occipital regions and
      lower FC with bilateral supramarginal gyrus. Right cerebellar to right frontal
      connectivity is also indicative of poor reading recall. We examine these and
      other differences between the two predictive FC networks, providing new insight
      into the task-dependent nature of FC-based performance metrics.

PMID- 29031533
TI  - Structural changes in brain morphology induced by brief periods of repetitive
      sensory stimulation.
AB  - There is a growing interest in identifying the neural mechanisms by which the
      human brain allows for improving performance. Tactile perceptual measurements,
      e.g. two-point discrimination (2ptD), can be used to investigate neural
      mechanisms of perception as well as perceptual improvement. Improvement can be
      induced in a practice-independent manner, e.g. in the tactile domain through
      repetitive somatosensory stimulation (rSS). With respect to tactile perception,
      the role of cortical excitability and activation within the somatosensory cortex
      has been investigated extensively. However, the role of structural properties,
      such as regional gray matter (GM) volume, is unknown. Using high resolution
      imaging and voxel-based morphometry (VBM), we sought to investigate how regional
      GM volume relates to individual 2ptD performance. Furthermore, we wanted to
      determine if electrical rSS has an influence on regional GM volume. 2ptD
      thresholds of the index fingers were assessed bilaterally. High-resolution (1
      mm3), T1-weighted images were obtained using a 3T scanner pre-and post
      stimulation. RSS was applied for 45 min to the dominant right hand, specifically
      to the fingertips of all fingers. At baseline, performance in the 2ptD task was
      associated with regional GM volume in the thalamus, primary somatosensory cortex,
      and primary visual cortex (negative association). After 45 min of rSS, we
      observed an improvement in 2ptD of the stimulated hand, whereas no improvement in
      tactile performance was seen on the non-stimulated side. These perceptual changes
      were accompanied by an increase in GM volume in the left somatosensory cortex and
      the degree of improvement correlated with GM volume changes in the insular
      cortex. Our results show that structural changes in the brain, specifically in
      regions receiving afferent input from the stimulated body site can be induced via
      a short-term intervention lasting only 45 min. However, the neurobiological
      correlates of these changes and the dynamics need to be further elucidated.

PMID- 29031532
TI  - Neuroimaging of vascular reserve in patients with cerebrovascular diseases.
AB  - Cerebrovascular reactivity, defined broadly as the ability of brain parenchyma to
      adjust cerebral blood flow in response to altered metabolic demand or a
      vasoactive stimulus, is being measured with increasing frequency and may have a
      use for portending new or recurrent stroke risk in patients with cerebrovascular
      disease. The purpose of this review is to outline (i) the physiological basis of
      variations in cerebrovascular reactivity, (ii) available approaches for measuring
      cerebrovascular reactivity in research and clinical settings, and (iii)
      clinically-relevant cerebrovascular reactivity findings in the context of
      patients with cerebrovascular disease, including atherosclerotic arterial steno
      occlusion, non-atherosclerotic arterial steno-occlusion, anemia, and aging.
      Literature references summarizing safety considerations for these procedures and
      future directions for standardizing protocols and post-processing procedures
      across centers are presented in the specific context of major unmet needs in the
      setting of cerebrovascular disease.

PMID- 29031534
TI  - Salidroside alleviates high glucose-induced oxidative stress and extracellular
      matrix accumulation in rat glomerular mesangial cells by the TXNIP-NLRP3
      inflammasome pathway.
AB  - Diabetic nephropathy (DN) is a metabolic disease characterized by mesangial cell
      proliferation and extracellular matrix (ECM) accumulation. Salidroside (SAL) is
      the major ingredient in Rhodiola rosea and possesses beneficial effects on DN.
      This study aimed to evaluate the effect of SAL on high glucose (HG)-induced
      oxidative stress and ECM accumulation and the underlying mechanism. Rat
      glomerular mesangial cells HBZY-1 were induced by high glucose (HG) in the
      presence or absence of SAL. Cell proliferation was measured by CCK-8 assay. The
      reactive oxygen species (ROS) level, malondialdehyde (MDA) level and superoxide
      dismutase (SOD) activity were detected to evaluate oxidative stress. The
      expression levels of ECM proteins including fibronectin (FN) and type IV collagen
      (Coll IV) were detected by qRT-PCR and western blot analysis. The expressions of
      thioredoxin-interacting protein (TXNIP), nod-like receptor protein 3 (NLRP3),
      apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 were
      assessed by western blot. Si-TXNIP or si-NC was transfected into HBZY-1 cells to
      inhibit TXNIP-NLRP3 inflammasome pathway. The results showed that SAL treatment
      alleviated HG-induced cell proliferation. SAL reduced the levels of ROS and MDA,
      and induced the SOD activity. Besides, the mRNA and protein expressions of FN and
      Coll IV were decreased by SAL. The expression levels of TXNIP, NLRP3, ASC, and
      caspase-1 were reduced in the SAL treated cells. In addition, TXNIP knockdown
      inhibited TXNIP-NLRP3 inflammasome activation and suppressed HG-induced cell
      proliferation, oxidative stress, and ECM accumulation. In conclusion, SAL
      alleviated HG-induced oxidative stress and ECM accumulation in rat glomerular
      mesangial cells by the TXNIP-NLRP3 inflammasome pathway.

PMID- 29031535
TI  - Baicalin protects AML-12 cells from lipotoxicity via the suppression of ER stress
      and TXNIP/NLRP3 inflammasome activation.
AB  - Baicalin (BA) is an active flavonoid compound originating from the root of
      Scutellaria baicalensis Georgi that has been reported to exert anti-inflammation
      and anti-oxidant effects in liver diseases with a long history. However, its
      protective and regulatory mechanisms on palmitic acid (PA) induced hepatocyte
      lipotoxicity remain elusive. In the present work, we investigated the
      cytoprotective effects of BA in AML-12 hepatocytes against lipotoxicity by
      inhibiting ER stress, oxidative stress and apoptosis. Our results demonstrated
      that ER stress was induced by 400 MUM PA in AML-12 cells with elevated expression
      of ER stress marker IRE1alpha hyperphosphorylation. BA at 12.5 MUM and 25 MUM
      effectively inhibited the expression of p-IRE1alpha as TUDCA. Flow cytometry
      analysis and immunofluorescence staining revealed that PA-induced ROS and cell
      apoptosis were reversed by BA. Furthermore, western blotting revealed that PA
      challenged expressions of TXNIP and NLRP3 were dramatically suppressed by BA and
      TUDCA, suggesting that BA inhibited ER stress through a TXNIP/NLRP3 pathway.
      Overall, our results indicate that BA alleviates PA-induced cytotoxicity in AML
      12 cells via suppression of ER stress and TXNIP/NLRP3 inflammasome activation.
      These results provide a possible basis of the underlying mechanism and a new
      insight into the application for BA in the treatment of NAFLD.

PMID- 29031536
TI  - Extraction of carboxylic acid-containing diterpenoids from Dodonaea viscosa via
      pressurised hot water extraction.
AB  - Pressurised hot water extraction (PHWE) was employed to effect the extraction of
      two carboxylic acid-containing ent-labdane diterpenoids from Dodonaea viscosa.
      The different extraction profile provided by PHWE in this case suggests that this
      recently developed method also has applications as a complementary tool for
      natural products extraction.

PMID- 29031537
TI  - Silybin counteracts doxorubicin resistance by inhibiting GLUT1 expression.
AB  - Despite significant advances in the diagnosis and treatment of cancer, the
      development of drug resistance still remains one of the principal causes that
      hampers the effectiveness of the therapy. Emerging evidences support the idea
      that the dysregulated metabolism could be related to drug resistance. The major
      goal of this study was to target cancer metabolic pathways using new
      pharmacological approaches coming from natural sources in order to possibly
      prevent or overcome this phenomenon. Firstly, the metabolic profile of human
      colorectal adenocarcinoma cells sensitive (LoVo WT) and resistant to doxorubicin
      (LoVo DOX) was delineated demonstrating that resistant cells remodel their
      metabolism toward a glycolytic phenotype. In particular it was observed that
      doxorubicin-resistant cancer cells exhibit an increased dependency from glucose
      for their survival, associated with overexpression of the glycolytic pathway.
      Moreover, both GLUT1 mRNA and protein expression significantly increased in LoVo
      DOX cells. Given the results about the metabolic profile, silybin, modulator of
      GLUTs, was selected as potential candidate to overcome doxorubicin resistance
      and, intriguingly, data revealed not only that silybin is more active in
      resistant cells than in wild type cells, but also that the combined treatment
      with doxorubicin and silybin presents a synergistic effect in LoVo DOX cells.
      Although many unanswered questions still remain about the molecular mechanism of
      silybin, these data suggest that targeting GLUTs may be a good strategy to
      restore doxorubicin sensitivity and elude drug resistance.

PMID- 29031538
TI  - Everyday stress response targets in the science of behavior change.
AB  - Stress is an established risk factor for negative health outcomes, and responses
      to everyday stress can interfere with health behaviors such as exercise and
      sleep. In accordance with the Science of Behavior Change (SOBC) program, we apply
      an experimental medicine approach to identifying stress response targets,
      developing stress response assays, intervening upon these targets, and testing
      intervention effectiveness. We evaluate an ecologically valid, within-person
      approach to measuring the deleterious effects of everyday stress on physical
      activity and sleep patterns, examining multiple stress response components (i.e.,
      stress reactivity, stress recovery, and stress pile-up) as indexed by two key
      response indicators (negative affect and perseverative cognition). Our everyday
      stress response assay thus measures multiple malleable stress response targets
      that putatively shape daily health behaviors (physical activity and sleep). We
      hypothesize that larger reactivity, incomplete recovery, and more frequent stress
      responses (pile-up) will negatively impact health behavior enactment in daily
      life. We will identify stress-related reactivity, recovery, and response in the
      indicators using coordinated analyses across multiple naturalistic studies. These
      results are the basis for developing a new stress assay and replicating the
      initial findings in a new sample. This approach will advance our understanding of
      how specific aspects of everyday stress responses influence health behaviors, and
      can be used to develop and test an innovative ambulatory intervention for stress
      reduction in daily life to enhance health behaviors.

PMID- 29031539
TI  - Fetal surgery for myelomeningocele: After the Management of Myelomeningocele
      Study (MOMS).
AB  - Myelomeningocele (MMC) is the most frequently occurring congenital abnormality of
      the central nervous system and leads to significant physical disabilities.
      Historically treatment involved postnatal closure with management of the
      associated sequelae including ventricular shunting. The mechanism of neurologic
      damage that begins with abnormal neurulation followed by continued injury over
      the course of gestation made MMC a plausible candidate for in-utero surgical
      repair. Animal and early human studies demonstrated the feasibility of fetal
      closure. The benefit of in-utero closure was debated until the results of the
      prospective randomized multicenter Management of Myelomeningocele Study (MOMS
      trial) were published, demonstrating a decreased need for shunting, reversal of
      hindbrain herniation, and better neurologic function in the prenatal repair group
      compared to postnatal repair with maternal complications and prematurity as a
      trade-off. As such, fetal MMC closure has become a standard of care option for
      prenatally diagnosed spina bifida. This paper reviews the MOMS trial and the
      journey of fetal MMC closure since that time.

PMID- 29031540
TI  - Maternal uterine artery VEGF gene therapy for treatment of intrauterine growth
      restriction.
AB  - Intrauterine growth restriction (IUGR) is a serious pregnancy complication
      affecting approximately 8% of all pregnancies. The aetiology is believed to be
      insufficient maternal uteroplacental perfusion which prevents adequate nutrient
      and oxygen availability for the fetus. There is no treatment that can improve
      uteroplacental perfusion and thereby increase fetal growth in the uterus.
      Maternal uterine artery gene therapy presents a promising treatment strategy for
      IUGR, with the use of adenoviral vectors encoding for proteins such as Vascular
      Endothelial Growth Factor (VEGF) demonstrating improvements in fetal growth and
      neonatal outcome in preclinical studies. Mechanistically, maternal VEGF gene
      therapy delivered to the uterine arteries increases uterine blood flow and
      enhances vascular relaxation short term, while reducing vascular contractility
      long term. It also leads to vascular remodeling with increased endothelial cell
      proliferation in the perivascular adventitia of uterine arteries. Safety
      assessments suggest no vector spread to the fetus and no adverse risk to the
      mother or fetus; a clinical trial is in development. This article assesses
      research into VEGF maternal uterine artery directed gene therapy for IUGR,
      investigating the use of transgenes and vectors, their route of administration in
      obstetrics, and the steps that will be needed to take this treatment modality
      into the clinic.

PMID- 29031541
TI  - How to boost marine fungal research: A first step towards a multidisciplinary
      approach by combining molecular fungal ecology and natural products chemistry.
AB  - Marine fungi have attracted attention in recent years due to increased
      appreciation of their functional role in ecosystems and as important sources of
      new natural products. The concomitant development of various "omic" technologies
      has boosted fungal research in the fields of biodiversity, physiological ecology
      and natural product biosynthesis. Each of these research areas has its own
      research agenda, scientific language and quality standards, which have so far
      hindered an interdisciplinary exchange. Inter- and transdisciplinary interactions
      are, however, vital for: (i) a detailed understanding of the ecological role of
      marine fungi, (ii) unlocking their hidden potential for natural product
      discovery, and (iii) designing access routes for biotechnological production. In
      this review and opinion paper, we describe the two different "worlds" of marine
      fungal natural product chemists and marine fungal molecular ecologists. The
      individual scientific approaches and tools employed are summarised and explained,
      and enriched with a first common glossary. We propose a strategy to find a
      multidisciplinary approach towards a comprehensive view on marine fungi and their
      chemical potential.

PMID- 29031542
TI  - Complications and 30-Day readmission rates after craniotomy/craniectomy: A single
      Institutional study of 243 consecutive patients.
AB  - Early hospital readmission has become a proxy for quality of care and contributes
      significantly to high health care costs in the United States, with more than $20
      billion health care dollars are spent on 30-day readmission annually. Cranial
      neurosurgical procedures (i.e., craniotomy, craniectomy) are associated with high
      readmission rates; however, studies examining readmission after cranial
      procedures are limited and relatively unknown. The aim of this study is to
      identify the drivers of 30-day unplanned readmission in consecutive patients
      undergoing craniotomies and craniectomies. The medical records of 243 consecutive
      patients undergoing either craniotomy or craniectomy at a major academic
      institution in 2011 were reviewed. Patient demographics, comorbidities, intra-
      and post-operative complication rates were collected for each patient. We
      identified all unplanned readmissions within 30 days of discharge. A total of 10
      (4.1%) unplanned 30-day readmissions were identified. The mean +/- SD age was
      58.58 +/- 15.12 years. The most common indication for surgery was malignancy
      (63.4%) followed by Chiari malformation (10.3%), epilepsy (5.3%), and skull
      lesion/deformity (2.9%). The majority of patients presented to the emergency
      department from home (80%), while 10% were readmitted from a skilled nursing
      facility and 10% were readmitted from an acute rehabilitation institution. The
      most common presented symptoms for readmitted patients were fever/presumed
      infection (40%) and altered mental status (40%), followed by new sensory/motor
      deficits (30%). This study suggests that infection, altered mental status, and
      new sensory/motor deficits were the primary complications leading to unplanned 30
      day readmission after cranial neurosurgery.

PMID- 29031543
TI  - Down-regulation of TGF-beta RII expression is correlated with tumor growth and
      invasion in non-functioning pituitary adenomas.
AB  - The two types of TGF-beta receptors play a crucial role in TGF-beta signaling. It
      has been reported that TGF-beta signaling activity may be associated with the
      development and invasion of NFPAs. However, the role of TGF-beta receptor
      signaling in NFPAs has not been fully explored. In this study, the expression of
      TGF-beta RI and TGF-beta RII in normal anterior pituitaries, invasive NFPAs and
      non-invasive NFPAs was analyzed by qRT-PCR, western blot, and
      immunohistochemistry. We found that TGF-beta RII protein and mRNA levels
      gradually decreased from normal anterior pituitaries, noninvasive NFPAs to
      invasive NFPAs. There was no significant difference in the expression of TGF-beta
      RI mRNA and protein level between normal anterior pituitaries and NFPAs. PCNA
      mRNA level was significantly higher in the invasive NFPAs than noninvasive NFPAs
      and PCNA mRNA had a negative correlation with TGF-beta RII mRNA. We may draw the
      conclusion that low expression of TGF-beta RII may contribute to the development
      and invasion of NFPAs and TGF-beta RII promises to be a useful biomarker for the
      diagnosis of invasive NFPAs.

PMID- 29031544
TI  - Effects of augmented corticosterone in painted turtle eggs on offspring
      development and behavior.
AB  - Maternal stressors can play an integral role in offspring development and
      ultimate behaviors in many vertebrates. Increased circulating stress avoidance
      hormones can be reflected in elevated concentrations in ova, thus providing a
      potential mechanism for maternal stress to be transmitted to offspring even in
      taxa without parental care. In this study, we assessed the potential impacts of
      augmented stress avoidance hormones on offspring development and anti-predator
      behaviors in a freshwater turtle, Chrysemys picta. We exposed C. picta eggs to
      biologically relevant amounts of the stress avoidance hormone, corticosterone, as
      a proxy for maternal stressors. We allowed the eggs to incubate in the field,
      then measured offspring phenotypes, conducted performance trials, and simulated
      nest emergence in a field experiment. Exogenous corticosterone reduced
      survivorship to hatch, but did not affect incubation duration, offspring size,
      overwinter survival, or size after hibernation. In performance trials, this
      hormone treatment reduced the frequency of righting, yet enhanced the righting
      speed of neonates. Regardless, these performance differences did not detectably
      alter survivorship in the nest emergence experiment. These results lend insight
      into the potential effects of maternal stress levels on offspring phenotypes, as
      well as the robustness of offspring fitness to altered levels of maternal stress
      in freshwater turtles.

PMID- 29031545
TI  - Social modeling of eating mediated by mirror neuron activity: A causal model
      moderated by frontal asymmetry and BMI.
AB  - The social modeling of eating effect refers to the consistently demonstrated
      phenomenon that individuals tend to match their quantity of food intake to their
      eating companion. The current study sought to explore whether activity within the
      mirror neuron system (MNS) mediates the social modeling of eating effect as a
      function of EEG frontal asymmetry and body mass index (BMI). Under the guise of
      rating empathy, 93 female undergraduates viewed a female video confederate
      "incidentally" consume either a low or high intake of chips while
      electroencephalogram (EEG) activity was recorded. Subsequent ad libitum chip
      consumption was quantified. A first- and second-stage dual moderation model
      revealed that frontal asymmetry and BMI moderated an indirect effect of model
      consumption on participants' food consumption as mediated by MNS activity at
      electrode site C3, a3b3=-0.718, SE=0.365, 95% CI [-1.632, -0.161]. Left frontal
      asymmetry was associated with greater mu activity and a positive association
      between model and participant chip consumption, while right frontal asymmetry was
      associated with less mu activity and a negative association between model and
      participant consumption. Across all levels of frontal asymmetry, the effect was
      only significant among those with a BMI at the 50th percentile or lower. Thus,
      among leaner individuals, the MNS was demonstrated to mediate social modeling of
      eating, as moderated by frontal asymmetry. These findings are integrated within
      the normative account of social modeling of eating. It is proposed that the
      normative framework may benefit from consideration of both conscious and
      unconscious operation of intake norms.

PMID- 29031546
TI  - Influenza virus but not MERS coronavirus circulation in Iran, 2013-2016:
      Comparison between pilgrims and general population.
AB  - BACKGROUND: The pilgrimage to Mecca and Karbala bring many Muslims to a confined
      area. Respiratory tract infections are the most common diseases transmitted
      during mass gatherings in Hajj, Umrah and Karbala. The aim of this study was to
      determine and compare the prevalence of Middle East respiratory syndrome
      coronavirus (MERS-CoV) and influenza virus infections among Iranian general
      population and pilgrims with severe acute respiratory infections (SARI) returning
      from Mecca and Karbala during 2013-2016. METHODS: During 2013-2016, a total of
      42351 throat swabs were examined for presence of influenza viruses and MERS-CoV
      in Iranian general population and pilgrims returning from Mecca and Karbala with
      SARI by using one step RT-PCR kit. RESULTS: None of the patients had MERS-CoV but
      influenza viruses were detected in 12.7% with high circulation of influenza
      A/H1N1 (47.1%). CONCLUSION: This study showed the prevalence of influenza
      infections among Iranian pilgrims and general population and suggests continuing
      surveillance, infection control and appropriate vaccination especially nowadays
      that the risk of influenza pandemic threatens the world, meanwhile accurate
      screening for MERS-CoV is also recommended.

PMID- 29031547
TI  - Forebrain activation during social exposure in wild-type guppies.
AB  - The neural mechanisms regulating social behaviour have received extensive
      attention in recent years, with much focus on 'complex' forms of sociality.
      Comparatively little research has addressed fundamental social behaviour, such as
      grouping, which impacts multiple determinants of fitness, such as foraging and
      avoiding predation. We are interested in the degree to which brain areas that
      regulate other forms of sociality are also involved in grouping behaviour, and so
      we investigated shoal-elicited activation of the brain in the guppy (Poecilia
      reticulata). Guppies are small, social fish that live in the rivers of Trinidad
      and, like many social fish, exhibit preferences for larger shoals. We first
      confirmed that our study population of wild-type guppies preferred to join a
      larger shoal, and then investigated the activation of four brain regions proposed
      to be involved in social behaviour and reward (the preoptic area, the dorsal part
      of the ventral telencephalon, the ventral part of the ventral telencephalon, and
      the supracommissural part of the ventral pallium). Subjects were exposed to a
      large shoal, a small shoal, or to a tank empty of conspecifics, and we used
      immediate early gene expression (egr-1) to assess neuronal activation. We found
      increased activation in the preoptic area when fish were exposed to a large shoal
      compared to controls that had no social exposure. There were no significant
      differences in activation within the other brain areas examined, possibly because
      these brain areas are not key regulators of grouping behaviour or have only a
      secondary role. The higher activation of the preoptic area during social exposure
      suggests functional homology in this highly-conserved region across all
      vertebrates.

PMID- 29031548
TI  - Green tea protects against memory deficits related to maternal deprivation.
AB  - Maternal deprivation (MD) in early life affects the development of the brain,
      causing cognitive losses in adulthood. Oxidative imbalance may be one of the
      factors that trigger these deficits. Therapies with antioxidant components, like
      green tea from Camellia sinensis (GT) has been used to treat or prevent memory
      deficits in a variety of conditions related to oxidative stress. Here we
      demonstrate that memory deficits caused by MD can be prevented by GT antioxidant
      activity in hippocampus. Pregnant female rats were used. Her puppies were
      submitted to MD and intake of GT. Recognition and aversive memory were evaluated,
      as well as hippocampal oxidative status. Data showed that MD prejudice short and
      long-term recognition and aversive memory and that GT protected memory.
      Hippocampal reactive oxygen species levels were increased in MD rats; this
      increase was avoided by GT supplementation. GSH was decreased on hippocampus MD
      rats. GT did not avoid GSH decrease, but promote the increase of total
      antioxidant capacity in MD rats' hippocampus. In conclusion, GT protects against
      memory deficits related to MD, and one of the implicated mechanism seems to be
      the antioxidant effects of GT.

PMID- 29031549
TI  - Assessment of social behavior directed toward sick partners and its relation to
      central cytokine expression in rats.
AB  - Acute illness not only reduces the expression of social behavior by sick rodents,
      but can also lead to avoidance responses when detected by healthy, would-be
      social partners. When healthy animals interact with a sick partner, an intriguing
      question arises: does exposure to a sick conspecific elicit an anticipatory
      immune response that would facilitate defense against future infection? To
      address this question, healthy adult male Sprague-Dawley rats (N=64) were given a
      brief social interaction (30min) with a partner that was either sick (250MUg/kg
      injection with lipopolysaccharide [LPS] 3h prior to test) or healthy (sterile
      saline injection). During this exposure, social behavior directed toward the
      healthy or sick conspecific was measured. Additionally, the impact of housing
      condition was assessed, with rats group- or isolate-housed. Immediately after
      social interaction, brains were harvested for cytokine assessments within
      socially-relevant brain structures (olfactory bulb, amygdala, hippocampus and
      PVN). As expected, behavioral results demonstrated that (i) there was a robust
      suppression of social interaction directed against sick conspecifics; and (ii)
      isolate-housing generally increased social behavior. Furthermore, examination of
      central cytokine expression in healthy experimental subjects revealed a modest
      increase in TNF-alpha in rats that interacted with a sick social partner, but
      only in the olfactory bulb. Among the LPS-injected partners, expected increases
      in IL-1beta, IL-6, and TNF-alpha expression were observed across all brain sites.
      Moreover, IL-1beta and IL-6 expression was exacerbated in LPS-injected partners
      that interacted with isolate-housed experimental subjects. Together, these data
      replicate and extend our prior work showing that healthy rats avoid sick
      conspecifics, and provide preliminary evidence for an anticipatory cytokine
      response when rats are exposed to a sick partner. These data also provide new
      evidence to suggest that recent housing history potently modulates cytokine
      responses evoked by LPS.

PMID- 29031551
TI  - Neuroinflammation and neurosteroidogenesis: Reciprocal modulation during injury
      to the adult zebra finch brain.
AB  - Estrogens like estradiol (E2) via their receptors are pluripotent steroid
      hormones that exert a profound influence on the developing and adult brain in
      many vertebrates. In songbirds and mammals, acute brain injury resulting from
      mechanical damage, anoxia and ischemia rapidly upregulates aromatase and E2
      synthesis. Interestingly, this E2 provision occurs due to the induction of
      aromatase expression in reactive astrocytes in areas surrounding brain injury.
      The resultant increase in E2 is neuroprotective with established influences on
      apoptosis, gliosis, cytogenesis, neurogenesis and neuroinflammation.
      Correspondingly, E2 decreases secondary damage following acute brain trauma and
      may improve recovery. Until very recently however, the signals responsible for
      the induction of astrocytic aromatase expression in reactive astrocytes were
      unknown. In the current review, we discuss what is known about the role of
      astrocytic E2 in neuroprotection with a particular emphasis on a recently
      discovered interaction between neuroinflammatory and steroidogenic signaling in
      the zebra finch. We first describe the role of acute inflammatory signaling in
      the regulation of astrocytic aromatase and central E2 levels. Next, we discuss
      the emerging role of central E2 in the control of chronic neuroinflammation.
      Finally, we provide a framework for further work investigating the important role
      of the interaction between inflammatory and steroidogenic signaling in the
      protection of neural circuits and behavior following traumatic brain injury
      (TBI). We also highlight dimorphisms that point to important aspects of sex
      specific pathways that underlie the interactions of neuroinflammation and
      neurosteroidogenesis.

PMID- 29031550
TI  - Mechanisms for AgRP neuron-mediated regulation of appetitive behaviors in
      rodents.
AB  - The obesity epidemic is a major health and economic burden facing both developed
      and developing countries worldwide. Interrogation of the central and peripheral
      mechanisms regulating ingestive behaviors have primarily focused on food intake,
      and in the process uncovered a detailed neuroanatomical framework controlling
      this behavior. However, these studies have largely ignored the behaviors that
      bring animals, including humans, in contact with food. It is therefore useful to
      dichotomize ingestive behaviors as appetitive (motivation to find and store food)
      and consummatory (consumption of food once found), and utilize an animal model
      that naturally displays these behaviors. Recent advances in genetics have
      facilitated the identification of several neuronal populations critical for
      regulating ingestive behaviors in mice, and novel functions of these neurons and
      neuropeptides in regulating appetitive behaviors in Siberian hamsters, a natural
      model of food foraging and food hoarding, have been identified. To this end,
      hypothalamic agouti-related protein/neuropeptide Y expressing neurons (AgRP
      neurons) have emerged as a critical regulator of ingestive behaviors. Recent
      studies by Dr. Timothy Bartness and others have identified several discrete
      mechanisms through which peripheral endocrine signals regulate AgRP neurons to
      control food foraging, food hoarding, and food intake. We review here recent
      advances in our understanding of the neuroendocrine control of ingestive
      behaviors in Siberian hamsters and other laboratory rodents, and identify novel
      mechanisms through which AgRP neurons mediate appetitive and consummatory
      behaviors.

PMID- 29031552
TI  - AgRP knockdown blocks long-term appetitive, but not consummatory, feeding
      behaviors in Siberian hamsters.
AB  - Arcuate hypothalamus-derived agouti-related protein (AgRP) and neuropeptide Y
      (NPY) are critical for maintaining energy homeostasis. Fasting markedly
      upregulates AgRP/NPY expression and circulating ghrelin, and exogenous ghrelin
      treatment robustly increases acute food foraging and food intake, and chronic
      food hoarding behaviors in Siberian hamsters. We previously demonstrated that 3rd
      ventricular AgRP injection robustly stimulates acute and chronic food hoarding,
      largely independent of food foraging and intake. By contrast, 3rd ventricular NPY
      injection increases food foraging, food intake, and food hoarding, but this
      effect is transient and gone by 24h post-injection. Because of this discrepancy
      in AgRP/NPY-induced ingestive behaviors, we tested whether selective knockdown of
      AgRP blocks fasting and ghrelin-induced increases in food hoarding. AgRP gene
      knockdown by a novel DICER small interfering RNA (AgRP-DsiRNA) blocked food
      deprivation induced increases in AgRP expression, but had no effect on NPY
      expression. AgRP-DsiRNA attenuated acute (1day), and significantly decreased
      chronic (4-6days), food deprivation-induced increases in food hoarding. In
      addition, AgRP-DsiRNA treatment blocked exogenous ghrelin-induced increases in
      food hoarding through day 3, but had no effect on basal food foraging, food
      intake, or food hoarding prior to ghrelin treatment. Lastly, chronic AgRP
      knockdown had no effect on body mass, fat mass, or lean mass in either food
      deprived or ad libitum fed hamsters. These data collectively suggest that the
      prolonged increase in food hoarding behavior following energetic challenges, and
      food deprivation especially, is primarily regulated by downstream AgRP signaling.

PMID- 29031553
TI  - Relationship Between HIV and Depressive Symptomatology in Patients From Northern
      Portugal: Analysis of Individual, Health, and Social Predictors.
AB  - Depression is the most prevalent mental disorder in people living with HIV. Our
      study involved 371 participants in outpatient treatment for HIV in hospitals in
      northern Portugal. Participants were referred to the study by the attending
      physician/nurse, and data were collected through an individual interview at a
      single evaluation moment. Participants were mostly male (70%), with an average
      age of 46.63 years (SD = 11.77), and a known diagnosis of HIV for an average of
      10.13 years (SD = 6.42). Severe depressive symptoms were identified in 18% of
      participants. We identified several significant predictors of depressive
      symptoms: being female, being in a situation of social exclusion, having adverse
      experiences throughout life, infection by sexual contact in a stable marital
      relationship, daily concerns regarding health, negative family relationships, and
      dissatisfaction with social support. Findings suggest the need to include regular
      mental health assessments and referral for specialized psychological support
      services.

PMID- 29031554
TI  - Unruptured intracranial aneurysms: It is not a bomb!

PMID- 29031555
TI  - Beneficial effects of dietary restriction in aging brain.
AB  - Aging is a multifactorial complex process that leads to the deterioration of
      biological functions wherein its underlying mechanism is not fully elucidated. It
      affects the organism at the molecular and cellular level that contributes to the
      deterioration of structural integrity of the organs. The central nervous system
      is the most vulnerable organ affected by aging and its effect is highly
      heterogeneous. Aging causes alteration in the structure, metabolism and
      physiology of the brain leading to impaired cognitive and motor-neural functions.
      Dietary restriction (DR), a robust mechanism that extends lifespan in various
      organisms, ameliorates brain aging by reducing oxidative stress, improving
      mitochondrial function, activating anti-inflammatory responses, promoting
      neurogenesis and increasing synaptic plasticity. It also protects and prevents
      age-related structural changes. DR alleviates many age-associated diseases
      including neurodegeneration and improves cognitive functions. DR
      inhibits/activates nutrient signaling cascades such as insulin/IGF-1, mTOR, AMPK
      and sirtuins. Because of its sensitivity to energy status and hormones, AMPK is
      considered as the global nutrient sensor. This review will present an elucidative
      potential role of dietary restriction in the prevention of phenotypic features
      during aging in brain and its diverse mechanisms.

PMID- 29031556
TI  - Corrigendum to "Long-term results of a phase II study of gemcitabine and
      cisplatin chemotherapy combined with intensity-modulated radiotherapy in
      locoregionally advanced nasopharyngeal carcinoma" [Oral Oncol. 73 (2017) 118
      123].
AB  - OBJECTIVES: To evaluate long-term results of a phase II study of induction and
      adjuvant gemcitabine and cisplatin (GP) chemotherapy with intensity-modulated
      radiotherapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (NPC).
      MATERIALS AND METHODS: One hundred and twelve patients (Stage III: 65, IVA-B: 47)
      with locoregionally advanced NPC were enrolled in this study. All patients
      received induction chemotherapy consisting of 1000 mg/m2 gemcitabine on day 1 and
      8, and cisplatin 25 mg/m2 on day 1-3, every 3 weeks for 2 cycles. Adjuvant
      chemotherapy for 2 cycles of the same regime was given 28 days after the end of
      IMRT. The IMRT technique was utilized for all patients. RESULTS: In total, 97.3%
      patients completed 2 cycles of induction chemotherapy. The overall response rate
      (RR) of cervical lymph nodes was 89.0%. Acute toxicities were mainly grade 1-2
      myleosuppression and vomiting. And 83.9% patients completed 2 cycles of adjuvant
      chemotherapy. All patients finished IMRT with RR at the end of IMRT for
      nasopharynx, lymph nodes of neck and retropharyngeal area being 99.1%, 97.9% and
      97.7%, respectively. The 5-year local control, regional control, distant
      metastasis-free and overall survival rates were 93.2%, 92.3%, 89.0% and 82.1%,
      respectively. The 5-year overall survival of stage III and IVA-B were 87.0%, and
      75.5%, respectively. The incidence of grade 3-4 acute radiotherapy-related
      mucositis was 28.6%. Severe late toxicities were uncommon. CONCLUSION: IMRT
      combined with GP for locoregionally advanced NPC is well tolerated, effective,
      and convenient, and warrants further studies.

PMID- 29031557
TI  - Regulation of HC11 mouse breast epithelial cell differentiation by the E
      cadherin/Rac axis.
AB  - It was previously demonstrated that differentiation of some established breast
      epithelial cell lines requires confluence and stimulation with hydrocortisone,
      insulin and prolactin inducers. We and others previously demonstrated that E
      cadherin engagement, which is favored under conditions of confluence, increases
      the levels and activity of the Rac small GTPase. To investigate the functional
      relationship between the transforming ability of Rac and its role as an integral
      component of the differentiative E-cadherin signaling pathway, we introduced a
      mutationally activated form of Rac, RacV12, into the mouse breast epithelium
      derived cell line, HC11. Our results demonstrate that the strength of the Rac
      signal is key for the outcome of the differentiation process; cRac1 is critically
      required for differentiation, and at low levels, mutationally activated RacV12 is
      able to increase differentiation, presumably reinforcing the E-cadherin/Rac
      differentiative signal. However, high RacV12 expression blocked differentiation
      concomitant with E-cadherin downregulation, while inducing neoplastic
      transformation. Therefore, the intensity of the Rac signal is a central
      determinant in the balance between cell proliferation vs differentiation, two
      fundamentally opposed processes, a finding which could also have important
      therapeutic implications.

PMID- 29031558
TI  - Resolution and identification of scalemic caged xanthones from the leaf extract
      of Garcinia propinqua having potent cytotoxicities against colon cancer cells.
AB  - A new scalemic 8,8a-dihydro caged xanthone (1) was isolated from the leaf extract
      of Garcinia propinqua. Five other known natural products, the three caged
      xanthones (2, 5 and 6) and the two neocaged xanthones, (3 and 4) were also
      isolated as scalemic mixtures. Their structures were characterized by
      spectroscopic methods. The enantiomeric ratios (er) of compounds 1-6 ranged from
      1:0.7 to 1:0.9. These compounds were also resolved by semipreparative chiral
      HPLC. The absolute configurations of (+)-2 and (+)-3 were determined by single
      crystal X-ray diffraction analysis using Cu Kalpha radiation while the absolute
      configurations of the other compounds were determined by comparisons of their ECD
      spectra. Compounds (-)-4, (+)-4, (-)-5, (+)-5, and (-)-6 showed potent
      cytotoxicities against a colon cancer cell line HCT116 with IC50 values of 2.60,
      7.02, 1.47, 3.37, and 4.14MUM, respectively, which were better than the standard
      control doxorubicin (IC50 9.74MUM).

PMID- 29031559
TI  - New sesquiterpenoid isonitriles from three species of phyllidid nudibranchs.
AB  - Chemical investigation of the two nudibranch species Phyllidiella pustulosa and
      Phyllidia ocellata collected in Queensland, Australia, provided new stereoisomers
      of 4-isocyano-9-amorphene (1) and of 10-isocyano-4-amorphene (2), respectively. A
      specimen of Phyllidia picta collected from Bali, Indonesia, contained the axane
      sesquiterpenoids pictaisonitrile-1 (3) and pictaisonitrile-2 (4). The planar
      structures were elucidated using 1D and 2D NMR spectroscopy, while relative
      configurations were established using NOESY correlations, coupling constant data,
      and comparison with literature data.

PMID- 29031560
TI  - Expanding nursing knowledge for therapeutic plasma exchange a literature review
      paper.

PMID- 29031561
TI  - A century of introductions by coastal sessile marine invertebrates in Angola,
      South East Atlantic Ocean.
AB  - South Atlantic studies referring to non-native taxa are mostly restricted to
      Argentinean, Brazilian, and South African coasts. In this study we examined the
      literature to provide a list of sessile marine invertebrates along the Angolan
      coast, to infer its introduction status according to their biogeographical
      distribution and natural history. We reported 29 non-native and 7 cryptogenic
      species, a small number when compared to other South Atlantic regions of similar
      extension. Half of the non-native species were reported for Luanda. The majority
      of the introduced species had a northern hemisphere origin, a consequence of the
      main introduction route being from the North Atlantic/Mediterranean Sea during
      the Portuguese colonization. This is the first comprehensive assessment of this
      kind for the Angolan coast and the diversity of introduced species is certainly
      underestimated. Regular and rigorous assessments and monitoring of introduced
      marine species will help to understand the vectors, routes and time of
      introductions.

PMID- 29031562
TI  - Marine litter at the seafloor - Abundance and composition in the North Sea and
      the Baltic Sea.
AB  - Litter is present in all marine waters around the globe. It consists of several
      compound classes of which plastic is of special interest because of its high
      abundance and possible threat to marine organisms. The regional distribution,
      composition and abundance of large litter items (LI) at the sea floor of the
      North Sea and the Baltic Sea were investigated based on 175 bottom trawls between
      2013 and 2015. Different types of marine litter >2.5cm were classified according
      to the protocol of the ICES International Bottom Trawl Survey. The results showed
      considerable geographical variation: In the North Sea, a mean litter abundance of
      16.8LI/km2 was found, whereas the litter abundance in the Baltic Sea was
      significantly lower (5.07LI/km2). In general, plastic represented 80% of the
      litter items. During the study, some methodical aspects with possible impact on
      the results were identified that need to be addressed in future sampling
      campaigns.

PMID- 29031563
TI  - Gender-Specific Association of Desacylated Ghrelin with Subclinical
      Atherosclerosis in the Metabolic Syndrome.
AB  - OBJECTIVE: Ghrelin, a gastric hormone with pleiotropic effects modulates vascular
      function and may influence atherosclerosis. Plasma ghrelin is reduced in the
      metabolic syndrome (MS), which is also characterized by early atherosclerosis.
      Ghrelin circulates in acylated (AG) and desacylated (DAG) forms. Their relative
      impact and that of gender on subclinical atherosclerosis in MS is unknown. AIM OF
      THE STUDY: To investigate potential associations of total, AG and DAG with
      carotid atherosclerosis and with gender in the MS. METHODS: Plasma total ghrelin,
      AG, DAG and carotid artery IMT (cIMT) were measured in 46 MS patients (NCEP-ATP
      III criteria, 22M/24F). RESULTS: Compared with males, females had higher (p
      <0.05) total and DAG. In the association analysis, age and plasma glucose were
      positively (p <0.05) correlated with cIMT in all MS patients. The positive (p
      <0.05) association between cIMT and age was also confirmed in males, while that
      between cIMT and glucose was significant in women. In contrast, neither total
      ghrelin nor AG and DAG were associated with cIMT in all MS patients nor in the
      male subgroup. In females, a negative (p <0.05) association between carotid
      artery IMT, DAG and glucose was detected, but not between cIMT, total ghrelin and
      AG. In multivariate modeling, DAG remained negatively (p <0.05) associated with
      cIMT after adjusting for plasma glucose and cardiovascular risk factors.
      CONCLUSIONS: These data indicate a negative independent association between DAG
      and cIMT in middle-aged women with the MS and suggest a gender-specific
      modulatory function of DAG in the development of atherosclerosis.

PMID- 29031564
TI  - eIF3a: A new anticancer drug target in the eIF family.
AB  - eIF3a is the largest subunit of eIF3, which is a key player in all steps of
      translation initiation. During the past years, eIF3a is recognized as a proto
      oncogene, which is an important discovery in this field. It is widely reported to
      be correlated with cancer occurrence, metastasis, prognosis, and therapeutic
      response. Recently, the mechanisms of eIF3a action in the carcinogenesis are
      unveiled gradually. A number of cellular, physiological, and pathological
      processes involving eIF3a are identified. Most importantly, it is emerging as a
      new potential drug target in the eIF family, and some small molecule inhibitors
      are being developed. Thus, we perform a critical review of recent advances in
      understanding eIF3a physiological and pathological functions, with specific focus
      on its role in cancer and anticancer drug targets.

PMID- 29031565
TI  - Quantified postsurgical small cell size CTCs and EpCAM+ circulating tumor stem
      cells with cytogenetic abnormalities in hepatocellular carcinoma patients
      determine cancer relapse.
AB  - Detection of hepatocellular carcinoma circulating tumor cells performed with
      conventional strategies, is significantly limited due to inherently heterogeneous
      and dynamic expression of EpCAM, as well as degradation of cytokeratins during
      epithelial-to-mesenchymal transition, which inevitably lead to non-negligible
      false negative detection of such "uncapturable and invisible" CTCs. A novel SE
      iFISH strategy, improved for detection of HCC CTCs in this study, was applied to
      comprehensively detect, in situ phenotypically and karyotypically characterize
      hepatocellular and cholangiocarcinoma CTCs (CD45-/CD31-) in patients subjected to
      surgical resection. Clinical significance of diverse subtypes of CTC was
      systematically investigated. Existence of small cell size CTCs (<=5 MUm of WBCs)
      with cytogenetic abnormality of aneuploid chromosome 8, which constituted
      majority of the detected CTCs in HCC patients, was demonstrated for the first
      time. The stemness marker EpCAM+ aneuploid circulating tumor stem cells (CTSCs),
      and EpCAM- small CTCs with trisomy 8, promote tumor growth. Postsurgical quantity
      of small triploid CTCs (>=5 cells/6 ml blood), multiploid (>=pentasomy 8) CTSCs
      or CTM (either one >= 1) significantly correlated to HCC patients' poor
      prognosis, indicating that detection of those specific subtypes of CTCs and CTSCs
      in post-operative patients help predict neoplasm recurrence.

PMID- 29031566
TI  - High NRF2 expression controls endoplasmic reticulum stress induced apoptosis in
      multiple myeloma.
AB  - Multiple myeloma (MM) is an incurable disease characterized by clonal plasma cell
      proliferation. The stress response transcription factor Nuclear factor erythroid
      2 [NF-E2]-related factor 2 (NRF2) is known to be activated in MM in response to
      proteasome inhibitors (PI). Here, we hypothesize that the transcription factor
      NRF2 whose physiological role is to protect cells from reactive oxygen species
      via the regulation of drug metabolism and antioxidant gene plays an important
      role in MM cells survival and proliferation. We report for the first time that
      NRF2 is constitutively activated in circa 50% of MM primary samples and all MM
      cell lines. Moreover, genetic inhibition of constitutively expressed NRF2 reduced
      MM cell viability. We confirm that PI induced further expression of NRF2 in MM
      cell lines and primary MM. Furthermore, genetic inhibition of NRF2 of PI treated
      MM cells increased ER-stress through the regulation of CCAAT-enhancer-binding
      protein homologous protein (CHOP). Finally, inhibition of NRF2 in combination
      with PI treatment significantly increased apoptosis in MM cells. Here we identify
      NRF2 as a key regulator of MM survival in treatment naive and PI treated cells.

PMID- 29031567
TI  - Operation Breakthrough in 2017 Builds on the Past.
AB  - Operation Breakthrough (OB) is one of Missouri's largest early Head Start program
      and provides a variety of other services related to early childhood education and
      family support to low-income families who live in the poorest neighborhoods of
      Kansas City. Currently 96% of its preschool children enter kindergarten ready to
      learn. Current CLASSTM scores for Emotional Support, Organizational Support, and
      Instructional Support exceed national averages. In this paper, we describe the
      range of services it provides and give details of its organizational structure
      and budget.

PMID- 29031568
TI  - Anxiety Disorders in Old Age: Psychiatric Comorbidities, Quality of Life, and
      Prevalence According to Age, Gender, and Country.
AB  - OBJECTIVES: Previous estimates of the prevalence of anxiety disorders in late
      life vary greatly due to the lack of reliable diagnostic tools. This
      MentDis_ICF65+ study assessed 12-month prevalence rates of anxiety disorders and
      age- and gender-related differences in comorbidities, as well as impact on
      quality of life. DESIGN: The study used a cross-sectional multicenter survey.
      PARTICIPANTS: The study sample comprised 3,142 men and women aged 65 to 84 years,
      living in five European countries and Israel. MEASUREMENTS: Anxiety disorders
      were assessed using computer-assisted face-to-face interviews with an age
      appropriate diagnostic interview (CIDI65+). RESULTS: The prevalence of anxiety
      disorders was 17.2%. Agoraphobia was the most frequent disorder (4.9%), followed
      by panic disorder (3.8%), animal phobia (3.5%), general anxiety disorder (3.1%),
      post-traumatic stress disorder (1.4%), social phobia (1.3%), and obsessive
      compulsive disorder (0.8%). The prevalence rate of any anxiety disorder dropped
      by 40% to 47% in adults aged 75-84 years compared with those aged 65-74 years.
      Women were twice as likely to present with agoraphobia or general anxiety
      disorder as men. Only panic disorder and phobia were associated with comorbid
      major depression. The negative relationship with quality of life was limited to
      agoraphobia and generalized anxiety disorder. CONCLUSIONS: The age-appropriate
      CIDI65+ led to higher prevalence rates of anxiety disorders in the elderly, yet
      to weaker associations with comorbidities and impaired quality of life compared
      with previous studies.

PMID- 29031569
TI  - Response to: Measuring Loneliness: Are There Method Factors?

PMID- 29031570
TI  - Relationship among Depression, Gait Disturbance, Disability, and Neurobiological
      Abnormalities.

PMID- 29031571
TI  - Bipolar Disorder in Nursing Homes: Impact on Antipsychotic Use, Diagnosis
      Patterns, and New Diagnoses in People with Dementia.
AB  - OBJECTIVES: Nursing home quality measures include the proportion of residents who
      receive antipsychotics. Residents with bipolar disorder are included even though
      antipsychotics are FDA-approved for this indication. We evaluated how including
      residents with bipolar disorder impacted the antipsychotic use quality measure
      for long-stay residents. We evaluated the agreement of minimum data set (MDS)
      bipolar disorder diagnoses with Medicare data, whether dementia was diagnosed
      before bipolar disorder, and how less-specific bipolar disorder diagnoses
      impacted findings. DESIGN: Cross-sectional study. SETTING: Nursing homes in Iowa.
      PARTICIPANTS: 21,955 long-stay nursing home residents in the first quarter of
      2014. MEASUREMENTS: We identified antipsychotic use and bipolar disorder using
      MDS data. We compared MDS bipolar disorder diagnoses with Chronic Conditions
      Warehouse (CCW) "ever" bipolar disorder indicators, and prior year claims. We
      compared CCW condition onset dates to identify bipolar disorder diagnosed after
      dementia. RESULTS: The mean (SD) proportion receiving antipsychotics was 19.6%
      (11.1%) with bipolar disorder and 18.3% (10.8%) without. The positive predictive
      value (PPV) of MDS bipolar disorder diagnoses was 80.2% versus CCW lifetime
      indicators, and 74.6% versus claims. PPV decreased by 27.1% when "bipolar
      disorder, unspecified" and "other bipolar disorders" diagnoses were excluded.
      Nearly three-quarters of residents with bipolar disorder had dementia. Over half
      of those with dementia had dementia first per CCW records. This proportion was
      lower among those with more specific bipolar disorder diagnoses or MDS bipolar
      disorder indicators. CONCLUSIONS: Bipolar disorder in nursing home residents is
      often first diagnosed after dementia using nonspecific diagnoses. This practice
      deserves further evaluation.

PMID- 29031572
TI  - Nature, Nurture, Personality and Behavior: What's the Formula for Survival?

PMID- 29031574
TI  - A new all-purpose bilateral cleft lip repair: Bilateral cheiloplasty suitable for
      most conditions.
AB  - BACKGROUND: Only experienced surgeons can produce satisfactory results with most
      of the current surgical methods for bilateral cleft lip repair. The existing
      methods require not only preoperative orthodontic maneuvers but also accurate
      measurements for surgical design. We describe an easy-to-design and simple-to
      execute general purpose surgical technique to repair most bilateral cleft lips.
      METHODS: A retrospective review was performed for the patients who underwent
      bilateral cleft lip repair using our novel method between 2003 and 2016. The
      authors collected data from medical records, and the aesthetic results were
      judged using the aesthetic result categories by three independent surgeons;
      indirect anthropometry was applied to patients over 9 years of age. In addition,
      we investigated the complications, the reoperation rate, and the reasons for
      reoperation. RESULTS: Bilateral cleft lip surgery was performed in 146 cases
      between 2003 and 2016. Seventy-eight patients had bilateral complete cleft lips,
      47 patients had bilateral incomplete cleft lips, and 21 patients had bilateral
      complete and incomplete cleft lips (asymmetric patients). There were no acute
      complications requiring re-surgery, such as wound dehiscence, hematoma, and
      infection. According to aesthetic classification, 74 patients (51%) were
      classified into category I and 72 patients (49%) into category II; no patients
      were classified into categories III and IV. Seventy patients (48%) underwent
      secondary lip operations. In anthropometry, the measurements were observed to be
      symmetrical; left and right measurement data were not significantly different.
      The main purposes of the revision were excision of widened philtral scars (42
      cases) and correction of lateral vermilion bulging (28 cases). CONCLUSIONS: We
      have found our novel technique to be simple and capable of providing consistent,
      reproducible, and reliable results.

PMID- 29031573
TI  - Aerosol furosemide for dyspnea: Controlled delivery does not improve
      effectiveness.
AB  - Aerosolized furosemide has been shown to relieve dyspnea; nevertheless, all
      published studies have shown great variability in response. This dyspnea relief
      is thought to result from the stimulation of slowly adapting pulmonary stretch
      receptors simulating larger tidal volume. We hypothesized that better control
      over aerosol administration would produce more consistent dyspnea relief; we used
      a clinical ventilator to control inspiratory flow and tidal volume. Twelve
      healthy volunteers inhaled furosemide (40mg) or placebo in a double blind,
      randomized, crossover study. Breathing Discomfort was induced by hypercapnia
      during constrained ventilation before and after treatment. Both treatments
      reduced breathing discomfort by 20% full scale. Effectiveness of aerosol
      furosemide treatment was weakly correlated with larger tidal volume. Response to
      inhaled furosemide was inversely correlated to furosemide blood level, suggesting
      that variation among subjects in the fate of deposited drug may determine
      effectiveness. We conclude that control of aerosol delivery conditions does not
      improve consistency of treatment effect; we cannot, however, rule out placebo
      effect.

PMID- 29031575
TI  - Debunking the myth of e-cigarettes: A case of free flap compromise due to e
      cigarette use within the first 24 hours.

PMID- 29031576
TI  - Acute and long-term effects of trophic exposure to silver nanospheres in the
      central nervous system of a neotropical fish Hoplias intermedius.
AB  - Nanotechnologies are at the center of societal interest, due to their broad
      spectrum of application in different industrial products. The current concern
      about nanomaterials (NMs) is the potential risks they carry for human health and
      the environment. Considering that NMs can reach bodies of water, there is a need
      for studying the toxic effects of NMs on aquatic organisms. Among the NMs' toxic
      effects on fish, the interactions between NMs and the nervous system are yet to
      be understood. For this reason, our goal was to assess the neurotoxicity of
      polyvinylpyrrolidone coated silver nanospheres [AgNS (PVP coated)] and compare
      their effects in relation to silver ions (Ag+) in carnivorous Hoplias intermedius
      fish after acute and subchronic trophic exposure through the analysis of
      morphological (retina), biochemical (brain) and genetic biomarkers (brain and
      blood). For morphological biomarkers, damage by AgNS (PVP coated) in retina was
      found, including morphological changes in rods, cones, hemorrhage and epithelium
      rupture, and also deposition of AgNS (PVP coated) in retina and sclera. In the
      brain biomarkers, AgNS (PVP coated) did not disturb acetylcholinesterase
      activity. However, lowered migration of the DNA tail in the Comet Assay of blood
      and brain cells was observed for all doses of AgNS (PVP coated), for both acute
      and subchronic bioassays, and in a dose-dependent manner in acute exposure. Ag+
      also reduced the level of DNA damage only under subchronic conditions in the
      brain cells. In general, the results demonstrated that AgNS (PVP coated) do not
      cause similar effects in relation to Ag+. Moreover, the lowered level of DNA
      damage detected by Comet Assay suggests that AgNS (PVP coated) directly interacts
      with DNA of brain and blood cells, inducing DNA-DNA or DNA-protein crosslinks.
      Therefore, the AgNS (PVP coated) accumulating, particularly in the retina, can
      lead to a competitive disadvantage for fish, compromising their survival.

PMID- 29031577
TI  - Structural biology of GABAB receptor.
AB  - Metabotropic GABAB receptor is a G protein-coupled receptor (GPCR) that mediates
      slow and prolonged inhibitory neurotransmission in the brain. It functions as a
      constitutive heterodimer composed of the GABAB1 and GABAB2 subunits. Each subunit
      contains three domains; the extracellular Venus flytrap module, seven-helix
      transmembrane region and cytoplasmic tail. In recent years, the three-dimensional
      structures of GABAB receptor extracellular and intracellular domains have been
      elucidated. These structures reveal the molecular basis of ligand recognition,
      receptor heterodimerization and receptor activation. Here we provide a brief
      review of the GABAB receptor structures, with an emphasis on describing the
      different ligand-bound states of the receptor. We will also compare these with
      the known structures of related GPCRs to shed light on the molecular mechanisms
      of activation and regulation in the GABAB system, as well as GPCR dimers in
      general. This article is part of the "Special Issue Dedicated to Norman G.
      Bowery".

PMID- 29031578
TI  - Short-term exposure to bisphenol A affects water and salt intakes differently in
      male and ovariectomised female rats.
AB  - Thirst and sodium appetite are motivational states that lead to the search for
      and ingestion of water and sodium, thus contributing to maintenance of
      hydromineral balance. Oestrogens affect fluid intake and sodium preference.
      Bisphenol A (BPA) is an environmental endocrine-disrupting substance with
      oestrogenic activity. Whether there are sex differences in the ingestive effects
      of BPA is unknown. Therefore, the aim of the present work was to determine the
      effect of short-term treatment of low doses of BPA on thirst and sodium appetite
      in adult male and ovariectomised Wistar rats. Rats were subcutaneously injected
      with either vehicle or 10, 50, 100, or 500 MUg/kg/day BPA for a week. Two-bottle
      tests (water and 2.7% NaCl solution) were conducted in the animals' home cages
      with and without 24 h water deprivation. BPA reduced water and 2.7% NaCl intakes
      in a sex-dependent-manner. Fluid intakes displayed inverted U-shaped dose
      response curves, with different dose dependencies in spontaneously drinker rats
      than after 24 h water deprivation dehydration. Future studies on the role of BPA
      in sex-dependent body fluid homeostasis should elucidate the effects of BPA on
      the neuroendocrine controls of thirst and salt appetite.

PMID- 29031579
TI  - CD4+ CD52lo T-cell expression contributes to the development of systemic lupus
      erythematosus.
AB  - The cell-surface glycoprotein CD52 is widely expressed in lymphocytes. CD4+CD52hi
      T cells are functioning suppressor CD4+T cells. We investigated the role of the
      immune regulation of CD4+CD52 T cells in systemic lupus erythematosus (SLE).
      CD4+CD52lo T cells were increased in SLE patients, in positive correlation with
      SLEDAI, anti-ds-DNA antibody, and IgG concentration. Circulating follicular
      helper-like T cells (Tfh-like cells) were also increased in SLE, in positive
      correlation with CD4+CD52lo T cells. Chemokine receptor 8 (CCR8) expression in
      CD4+CD52lo T cells was increased. In vitro experiments using CD4 T cells of SLE
      patients showed that thymus and activation-regulated chemokine (TARC), a ligand
      of CCR8, contributed to the development of CD4+CD52hi T cells into CD4+CD52lo T
      cells. Our findings suggest that CD4+CD52lo T-cell upregulation is involved in
      the production of pathogens by autoantibodies, and TARC may contribute to the
      development of SLE through an aberrant induction of CD4+CD52lo T cells.

PMID- 29031580
TI  - Prevalence and characteristics of coronary artery disease in heart failure with
      preserved and mid-range ejection fractions: A systematic angiography approach.
AB  - BACKGROUND: Guidelines recommend careful screening and treatment of coronary
      artery disease (CAD) in heart failure with preserved or mid-range ejection
      fraction (HFpEF/HFmEF). AIM: We aimed to determine the prevalence and
      characteristics of CAD using a prospective systematic coronary angiography
      approach. METHODS: A systematic coronary angiography protocol was applied in
      consecutive patients admitted for HFpEF/HFmEF during a 6-month period in a single
      centre. History of CAD and results of angiography, including revascularization,
      were reported. RESULTS: Of the 164 patients with HFpEF/HFmEF who were included,
      an angiography assessment was applied in 108 (66%) (median age: 79 years
      [interquartile range: 70-85 years]; 54% were women). In our analysis, 64% (95%
      confidence interval [CI] 55-73%) of patients had a significant coronary stenosis
      corresponding to a global CAD prevalence of 80% (95% CI 73-88%). The prevalence
      of CAD was similar for HFpEF and HFmEF. The left main coronary artery presented a
      significant stenosis in 6.5% of cases and 39% of patients had a two- or three
      vessel disease. The rate of significant coronary stenosis was non-significantly
      higher in patients with a history of CAD. Patients with HFpEF/HFmEF with and
      without CAD did not differ in clinically meaningful ways, in terms of symptoms or
      laboratory and echocardiography results. This strategy led to complete
      revascularization in 36% of patients with significant stenosis and in 23% of all
      patients with HFpEF/HFmEF. CONCLUSIONS: Our study differs from others in that we
      used a systematic angiography approach. The results suggest a much higher
      prevalence of CAD in HFpEF/HFmEF than previously reported and should encourage
      clinicians to aggressively identify this co-morbidity.

PMID- 29031581
TI  - Parent Perceptions of Mobile Device Use Among Preschool-Aged Children in Rural
      Head Start Centers.
AB  - OBJECTIVE: To describe child use and parents' beliefs and comfort with young
      children's use of mobile devices in low-income, rural communities. METHODS: This
      was a descriptive, cross-sectional study. The survey, which consisted of 18
      multiple-part questions, was distributed to families at 5 Head Start/preschool
      centers in Colorado. RESULTS: In total, 192 surveys were returned (28.5% response
      rate). Most children (92%) used a smartphone or tablet at some frequency and most
      parents (90%) had downloaded apps specifically for their child. Education and
      ethnicity were related to parents' technology beliefs. Parent comfort with
      technology was positively associated with greater child use of technology (P <
      .001). CONCLUSIONS AND IMPLICATIONS: Mobile device use was relatively high in
      this sample. Mobile devices appear to be a feasible platform to offer nutrition
      and physical activity education for this audience. Ensuring parent comfort with
      technology and apps will be important.

PMID- 29031582
TI  - Validation of a Shortened Version of the Children's Eating Behavior Questionnaire
      and Associations with BMI in a Clinical Sample of Latino Children.
AB  - OBJECTIVE: To examine the validity of the Children's Eating Behavior
      Questionnaire (CEBQ) through the associations of its 3 subscale scores (food
      responsiveness, slowness in eating, and satiety responsiveness) with body mass
      index (BMI). DESIGN: Cross-sectional study of baseline data from a clinic-based
      obesity prevention and control randomized controlled trial. PARTICIPANTS: Latino
      pediatric patients (n = 295) aged 5-11 years from a federally qualified health
      center in San Diego County, CA, with BMI percentiles ranging from 75.5 to 99.0.
      MAIN OUTCOME MEASURE: Child BMI-for-age percentile computed using the
      standardized program for the 2000 Centers for Disease Control and Prevention
      growth charts. ANALYSIS: Principal components analysis and multivariate linear
      regressions. RESULTS: Principal components analysis showed a factor structure
      relatively similar to that of the original 3 CEBQ subscales, with acceptable
      internal consistency and between-subscale correlations. Analyses demonstrated the
      validity of the 3 subscales: child BMI was positively associated with food
      responsiveness (beta = .336; P <= .001) and negatively associated with slowness
      in eating (beta = -.209; P <= .001) and satiety responsiveness (beta = -.211; P
      <= .001). CONCLUSIONS AND IMPLICATIONS: The 14-item CEBQ scale may be useful for
      assessing obesogenic eating behaviors of Latino children. Further study is needed
      to replicate these findings.

PMID- 29031583
TI  - Model selection for high b-value diffusion-weighted MRI of the prostate.
AB  - PURPOSE: To assess the abilities of the standard mono-exponential (ME), bi
      exponential (BE), diffusion kurtosis (DK) and stretched exponential (SE) models
      to characterize diffusion signal in malignant and prostatic tissues and determine
      which of the four models best characterizes these tissues on a per-voxel basis.
      MATERIALS AND METHODS: This institutional-review-board-approved, HIPAA-compliant,
      retrospective study included 55 patients (median age, 61years; range, 42-77years)
      with untreated, biopsy-proven PCa who underwent endorectal coil MRI at 3-Tesla,
      diffusion-weighted MRI acquired at eight b-values from 0 to 2000s/mm2. Estimated
      parameters were apparent diffusion coefficent (ME model); diffusion coefficients
      for the fast (Dfast) and slow (Dslow) components and fraction of fast component,
      ffast (BE model); diffusion coefficient D, and kurtosis K (DK model); distributed
      diffusion coefficient DDC and alpha for (SE model). For one region-of-interest
      (ROI) in PZ and another in PCa in each patient, the corrected Akaike information
      criterion (AICc) and the Akaike weight (w) were calculated for each voxel.
      RESULTS: Based on AICc and w, all non-monoexponential models outperformed the ME
      model in PZ and PCa. The DK model in PZ and SE model in PCa ROIs best fit the
      greatest average percentages of voxels (39% and 43%, respectively) and had the
      highest mean w (35+/-16*10-2 and 41+/-22*10-2, respectively). CONCLUSION: DK and
      SE models best fit DWI data in PZ and PCa, and non-ME models consistently
      outperformed the ME model. Voxel-wise mapping of the preferential model
      demonstrated that the vast majority of voxels in either tissue type were best fit
      with one of the non-monoexponential models. At the given SNR levels, the maximum
      b-value of 2000s/mm2 is not sufficiently high to identify the preferred non
      monoexponential model.

PMID- 29031584
TI  - Validation of diffusion measurements obtained on a 0.35T MR in Malawi: Important
      insights for radiologists in low income settings with low field MRI.
AB  - PURPOSE: To investigate the reliability of diffusion weighted image (DWI)
      measurements obtained on a 0.35T MR scanner in Malawi for malaria research.
      MATERIALS AND METHODS: The same healthy volunteers (n=6) were scanned on a 0.35T
      MR scanner in Malawi and a 3T scanner in the US. Three subjects had two repeated
      DWI scans at 0.35T. Due to scanner constraints, only three diffusion gradient
      directions for DWI on 0.35T could be obtained. An apparent diffusion coefficient
      (ADC) map was reconstructed from the 0.35T and the result was compared to
      standard DWI acquisition on the 3T scanner. The mean ADC from 15 different
      regions and the voxel-wise coefficient of variation (CV) were calculated to
      investigate the intra-scanner and inter-scanner variability. Reproducibility was
      calculated using intra-class correlation coefficient (ICC). RESULTS: The 0.35T
      intra-scanner ADC repeatability was high for all three subjects with repeated
      scans (ICC>0.7). The intra-scanner correlation between repeated scans was also
      high (r>0.67, p< 0.01). Comparing the ADC findings from the 0.35T and 3T MRs, the
      high inter-scanner correlation suggested that the 0.35T ADC results were valid
      (ICC>0.7, r>0.5, p<0.01). Voxel-wise CV revealed a few regions with larger
      variation (CV>20%), which were primarily located in peripheral regions and the
      boundary of lateral ventricles, and likely due to partial volume effects in low
      field scans. CONCLUSION: These findings support the validity of DWI obtained from
      low field MR scanners used in many low income countries.

PMID- 29031585
TI  - Exon-based phylogenomics strengthens the phylogeny of Neotropical cichlids and
      identifies remaining conflicting clades (Cichliformes: Cichlidae: Cichlinae).
AB  - The phenotypic, geographic, and species diversity of cichlid fishes have made
      them a group of great interest for studying evolutionary processes. Here we
      present a targeted-exon next-generation sequencing approach for investigating the
      evolutionary relationships of cichlid fishes (Cichlidae), with focus on the
      Neotropical subfamily Cichlinae using a set of 923 primarily single-copy exons
      designed through mining of the Nile tilapia (Oreochromis niloticus) genome.
      Sequence capture and assembly were robust, leading to a complete dataset of 415
      exons for 139 species (147 terminals) that consisted of 128 Neotropical species,
      six African taxa, and five Indo-Malagasy cichlids. Gene and species trees were
      calculated using alternative partitioning schemes and reconstruction methods. In
      general, all methods yielded similar topologies to previously hypothesized
      relationships within the Cichlinae and clarified several relationships that were
      previously poorly supported or in conflict. Additional work will be needed to
      fully resolve all aspects of Cichlinae phylogeny. Overall, this approach yielded
      a well-resolved phylogeny of Neotropical cichlids that will be of utility for
      future assessments of the evolutionary and ecological processes within this
      diverse group of fishes. Furthermore, the general methodology employed here of
      exon targeting and capture should be applicable to any group of organisms with
      the availability of a reference genome.

PMID- 29031586
TI  - Complement C5a/C5aR pathway potentiates the pathogenesis of gastric cancer by
      down-regulating p21 expression.
AB  - Although the complement C5a/C5aR pathway is suggested to play a critical role in
      tumor pathogenesis, the underlying mechanism has yet to be fully elucidated. In
      the present study, we found that in patients with gastric cancer in different
      clinical stages (from stageIto stage IV), both C5aR and p-PI3K/AKT levels were
      significantly higher in tumoral tissues than in adjacent non-tumoral tissues. In
      contrast, p21/p-p21 levels were significantly lower in tumoral tissues than in
      adjacent non-tumoral tissues. In vitro recombinant C5a administration remarkably
      promoted p-PI3K/p-AKT expression, but inhibited p21/p-p21 expression. Blockage of
      C5a/C5aR signaling with a C5aR antagonist reversed the C5a-induced inhibitory
      effect on p21/p-p21 expression. C5a administration to cells pre-treated with a
      PI3K inhibitor also prevented this inhibitory effect, suggesting the involvement
      of the PI3K/AKT signaling pathway in C5a/C5aR-mediated suppression of p21/p-p21
      expression. In vivo C5aR antagonist treatment caused significant reduction in
      tumor growth in mice, accompanied by a remarkable elevation in p21/p-p21
      expression and reduction in p-PI3K/AKT activation. These results indicate that
      the C5a/C5aR pathway promotes gastric cancer pathogenesis by suppressing p21/p
      p21 expression via activation of PI3K/AKT signaling.

PMID- 29031587
TI  - A modified von Bertalanffy growth model dependent on temperature and body size.
AB  - Fish growth models are widely used in fisheries as well in aquacultures and
      ecology. Water temperature is one of the most important factors determining the
      growth of fish. In the present study, we propose a growth model that includes the
      effect of water temperature on the growth in the von Bertalanffy growth model.
      Our model was applied to fit the growth data of bullhead (Cottus gobio), brown
      trout (Salmo trutta L.), juvenile salmon (Salmo salar), and Araucanian herring
      (Strangomera bentincki). The model reproduces the growth patterns of each species
      and fits a set of appropriate parameter values for each species. Moreover, the
      model reflects the seasonal growth rates quite well.

PMID- 29031588
TI  - Swertisin rich fraction from Enicostema littorale ameliorates hyperglycemia and
      hyperlipidemia in high-fat fed diet and low dose streptozotacin induced type 2
      diabetes mellitus in rats.
AB  - INTRODUCTION: Enicostema littorale blume (A. Raynal) is a traditional Indian
      plant belongs to the Gentianaceae family. A lot of research has been done on this
      plant for its antidiabetic activity. However, there are no reports on flavonoids
      from E. littorale for its antidiabetic activity and their mechanism of action.
      Thus, the aim of this study is to evaluate the antidiabetic activity of Swertisin
      rich flavonoid fraction (SRF) from Enicostema littorale blume and their mechanism
      of action. MATERIALS & METHODS: Type 2 Diabetes Mellitus rat model was
      established by inducing insulin resistance using high fat diet and low dose of
      streptozotacin injection and was authenticated by HOMA index. The antidiabetic
      effect of SRF was evaluated on diabetic rats to investigate its long term effects
      on fasting blood glucose, OGTT, weight of rats, insulin, liver profile, lipid
      profile, kidney profile, histopathology of liver and pancreas. In addition,
      antioxidant activity by lipid peroxidation and catalase assay, ex vivo assays and
      hepatic glycogen content were performed to determine its effect on glycogenesis
      and hepatic glucose production. Furthermore, the mechanism of action of SRF was
      evaluated by Real time PCR and the mRNA expression was quantified for Glucokinase
      (GCK), Insulin receptor substrate (IRS-1), Glucose transporter-2 (GLUT-2) and
      Glucose transporter-4 (GLUT-4) genes. RESULTS: Treatment of diabetic rats with
      SRF demonstrated significant (p<0.0001) dose dependant hypoglycemic activity as
      compared to positive control metformin group. A decrease in liver, lipid and
      kidney function tests was seen as compared to diabetic control indicating
      normalization of organ function tests. Also, antioxidant activity showed
      significant decrease in malondialdehyde (MDA) content in liver (p<0.001) as
      compared to pancreas and increased catalytic activity in liver, kidney, spleen
      and pancreas. The hepatic glycogen content was significantly (p<0.001) increased
      in SRF treated rats indicating its inhibition of hepatic glucose production.
      Furthermore, ex vivo assays showed the significant (p<0.05) increase in glucose
      uptake by diaphragm. The mRNA expression for GCK, IRS-1, GLUT-2 and GLUT-4 genes
      showed significant up regulation as compared to diabetic control indicating its
      mechanism via insulin signalling pathway. CONCLUSION: The studies suggest that
      SRF ameliorates the insulin resistance by increasing glucose uptake and
      sensitizing cells towards insulin via IRS1/PI3K/Akt2 pathway.

PMID- 29031589
TI  - Implicit evaluations and physiological threat responses in people with persistent
      low back pain and fear of bending.
AB  - BACKGROUND AND AIMS: Pain and protective behaviour are dependent on implicit
      evaluations of danger to the body. However, current assessment of perceived
      danger relies on self-report, on information of which the person is aware and
      willing to disclose. To overcome this limitation, attempts have been made to
      investigate implicit evaluation of movement-related threatening images in people
      with persistent low back pain (PLBP) and pain-related fear. Lack of specificity
      of the sample and stimuli limited those explorations. This study investigated
      implicit evaluations and physiological responses to images of tasks commonly
      reported as threatening by people with PLBP: bending and lifting. We hypothesized
      that people who differ in self-reported fear of bending with a flexed lumbar
      spine (fear of bending) would also differ in implicit evaluations and
      physiological responses. METHODS: This study used a convenience sample of 44
      people (54% female) with PLBP, who differed in self-reported fear of bending.
      Participants completed a picture-viewing paradigm with pleasant, neutral and
      unpleasant images, and images of people bending and lifting with a flexed lumbar
      spine ('round-back') to assess physiological responses (eye-blink startle
      modulation, skin conductance). They also completed an implicit association test
      (IAT) and an affective priming task (APT). Both assessed implicit associations
      between (i) images of people bending/lifting with a flexed lumbar spine posture
      ('round-back' posture) or bending/lifting with a straight lumbar spine posture
      ('straight-back' posture), and (ii) perceived threat (safe vs. dangerous).
      RESULTS: An implicit association between 'danger' and 'round-back'
      bending/lifting was evident in all participants (IAT (0.5, CI [0.3; 0.6];
      p<0.001) and APT (24.2, CI [4.2; 44.3]; p=0.019)), and unrelated to self-reported
      fear of bending (IAT (r=-0.24, 95% CI [-0.5, 0.04], p=0.117) and APT (r=-0.00,
      95% CI [-0.3, 0.3], p=0.985)). Levels of self-reported fear of bending were not
      associated with eye-blink startle (F(3, 114)=0.7, p=0.548) or skin conductance
      responses (F(3, 126)=0.4, p=0.780) to pictures of bending/lifting. CONCLUSIONS:
      Contrary to our expectation, self-reported fear of bending was not related to
      physiological startle response or implicit measures. People with PLBP as a group
      (irrespective of fear levels) showed an implicit association between images of a
      round-back bending/lifting posture and danger, but did not display elevated
      physiological responses to these images. These results provide insight to the
      understanding of the relationship between pain and fear of movement.
      IMPLICATIONS: The potential clinical implications of our findings are twofold.
      First, these results indicate that self-report measures do not always reflect
      implicit associations between particular movements and threat. Implicit
      association tasks may help overcome this limitation. Second, a lack of the
      predicted physiological and behavioural responses may reflect that the
      visualization of a threatening task by people in pain does not elicit the same
      physiological defensive responses measured in people with fear of specific
      objects. It may be necessary to expose the person to the actual movement to
      elicit threat-responses. Together, these results are consistent with current
      views of the role of 'fear' in the fear-avoidance model, in which a fear response
      may only be elicited when the threat is unavoidable.

PMID- 29031590
TI  - Association Between Iron-Deficiency Anemia and Hypophosphatemia.

PMID- 29031591
TI  - Implications of Anomalous Left Coronary Artery Origin.

PMID- 29031592
TI  - A Traveler's Unwanted Souvenir.

PMID- 29031593
TI  - A Closer Look at Frederic Chopin's Cause of Death.

PMID- 29031594
TI  - The Latest Scoop: A Rare Case of Vitamin D Toxicity.

PMID- 29031595
TI  - Unexpected Diagnosis in a Man with Painful and Swollen Leg.

PMID- 29031596
TI  - The ranking of scientists based on scientific publications assessment.
AB  - It is generally accepted that the scientific impact factor (Web of Science) and
      the total number of citations of the articles published in a journal, are the
      most relevant parameters of the journal's significance. However, the significance
      of scientists is much more complicated to establish and the value of their
      scientific production cannot be directly reflected by the importance of the
      journals in which their articles are published. Evaluating the significance of
      scientists' accomplishments involves more complicated metrics than just their
      publication records. Based on a long term of academic experience, the author
      proposes objective criteria to estimate the scientific merit of an individual's
      publication record. This metric can serve as a pragmatic tool and the nidus for
      discussion within the readership of this journal.

PMID- 29031597
TI  - Lower airway microbiota and mycobiota in children with severe asthma.

PMID- 29031598
TI  - Clinical relevance of sensitization to hydrolyzed wheat protein in wheat
      sensitized subjects.

PMID- 29031599
TI  - Interaction of DJ-1 with Lyn is essential for IgE-mediated stimulation of human
      mast cells.
AB  - BACKGROUND: DJ-1 is a redox-sensitive protein with multiple roles in cell
      homeostasis, levels of which are altered in patients with mast cell (MC)-related
      disorders. However, whether DJ-1 can regulate human MC function is unknown.
      OBJECTIVE: We sought to investigate the potential role of DJ-1 in the responses
      of human MCs to antigen stimulation. METHODS: DJ-1 was silenced in human CD34+
      derived MCs and in the LAD2 MC line by using lentiviral short hairpin RNA
      constructs. Release of beta-hexosaminidase, prostaglandin D2, and GM-CSF and
      changes in reactive oxygen species levels were measured after FcepsilonRI
      engagement. Enzymatic assays, sucrose density gradient centrifugation,
      immunoprecipitation, dot and Western blotting, and confocal imaging were
      performed for signaling, cellular localization, and coassociation studies.
      RESULTS: DJ-1 knockdown substantially reduced mediator release, as well as Lyn
      kinase and spleen tyrosine kinase activation and signaling through mechanisms
      that appeared largely unrelated to DJ-1 antioxidant activity. Following
      FcepsilonRI activation, nonoxidized rather than oxidized DJ-1 translocated to
      lipid rafts, where it associated with Lyn, an interaction that appeared critical
      for maximal Lyn activation and initiation of signaling. Using purified
      recombinant proteins, we demonstrated that DJ-1 directly bound to Lyn but not to
      other Src kinases, and this interaction was specific for human but not mouse
      proteins. In addition, DJ-1 reduced Src homology 2 domain-containing phosphatase
      2 phosphatase activity by scavenging reactive oxygen species, thus preventing
      spleen tyrosine kinase dephosphorylation and perpetuating MC signaling.
      CONCLUSION: We demonstrate a novel role for DJ-1 in the early activation of Lyn
      by FcepsilonRI, which is essential for human MC responses and provides the basis
      for an alternative target in allergic disease therapy.

PMID- 29031600
TI  - Transcriptional determinants of individualized inflammatory responses at
      anatomically separate sites.

PMID- 29031601
TI  - Enhancing Generalization of Visuomotor Adaptation by Inducing Use-dependent
      Learning.
AB  - Learning a motor task in one condition typically generalizes to another, although
      it is unclear why it generalizes substantially in certain situations, but only
      partially in other situations (e.g., across movement directions and motor
      effectors). Here, we demonstrate that generalization of motor learning across
      directions and effectors can be enhanced substantially by inducing use-dependent
      learning, that is, by having subjects experience motor actions associated with a
      desired trajectory repeatedly during reaching movements. In Experiments 1 and 2,
      healthy human adults adapted to a visuomotor rotation while concurrently
      experiencing repetitive passive movements guided by a robot. This manipulation
      increased the extent of generalization across movement directions (Expt. 1) and
      across the arms (Expt. 2) by up to 50% and 42%, respectively, indicating crucial
      contribution of use-dependent learning to motor generalization. In Experiment 3,
      we applied repetitive transcranial magnetic stimulation (rTMS) to the left
      primary motor cortex (M1) of the human subjects prior to passive training with
      the right arm to increase cortical excitability. This intervention resulted in
      increased motor-evoked potentials (MEPs) and decreased short-interval
      intracortical inhibition (SICI) in the rTMS group, but not in the sham group.
      These changes observed in the rTMS group were accompanied by enhanced
      generalization of visuomotor adaptation across the arms, which was not the case
      in the sham group. Collectively, these findings confirm the involvement of M1 in
      use-dependent learning, and suggest that use-dependent learning can contribute
      not only to motor learning, but also to motor generalization.

PMID- 29031602
TI  - Microstructural MRI Basis of the Cognitive Functions in Patients with
      Spinocerebellar Ataxia Type 2.
AB  - Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative
      disease involving the cerebellum. The particular atrophy pattern results in some
      typical clinical features mainly including motor deficits. In addition, the
      presence of cognitive impairments, involving language, visuospatial and executive
      functions, has been also shown in SCA2 patients and it is now widely accepted as
      a feature of the disease. The aim of the study is to investigate the
      microstructural patterns and the anatomo-functional substrate that could account
      for the cognitive symptomatology observed in SCA2 patients. In the present study,
      diffusion tensor imaging (DTI) based-tractography was performed to map the main
      cerebellar white matter (WM) bundles, such as Middle and Superior Cerebellar
      Peduncles, connecting cerebellum with higher order cerebral regions. Damage
      related diffusivity measures were used to determine the pattern of pathological
      changes of cerebellar WM microstructure in patients affected by SCA2 and
      correlated with the patients' cognitive scores. Our results provide the first
      evidence that WM diffusivity is altered in the presence of the cerebellar
      cortical degeneration associated with SCA2 thus resulting in a cerebello-cerebral
      dysregulation that may account for the specificity of cognitive symptomatology
      observed in patients.

PMID- 29031604
TI  - Sex Mediates the Effects of High-Definition Transcranial Direct Current
      Stimulation on "Mind-Reading".
AB  - Sex differences in social cognitive ability are well established, including
      measures of Theory of Mind (ToM). The aim of this study was to investigate if sex
      mediates the effects of high-definition transcranial direct current stimulation
      (HD-tDCS) administered to a key hub of the social brain (i.e., the dorsomedial
      prefrontal cortex, dmPFC) on the Reading the Mind in the Eyes Test (RMET). Forty
      healthy young adults (18-35 years) were randomly allocated to receive either
      anodal or cathodal HD-tDCS in sham HD-tDCS controlled, double blind designs. In
      each of the two sessions, subjects completed the RMET. Anodal stimulation to the
      dmPFC increased accuracy on the RMET in females only. To assure regional
      specificity we performed a follow-up study stimulating the right temporoparietal
      junction and found no effect in either sex. The current study is the first to
      show improved performance on the RMET after tDCS to the dmPFC in females only.
      The polarity-specific effects and use of focal HD-tDCS provide evidence for sex
      dependent differences in dmPFC function in relation to the RMET. Future studies
      using tDCS to study or improve ToM, need to consider sex.

PMID- 29031603
TI  - Xanthurenic Acid Formation from 3-Hydroxykynurenine in the Mammalian Brain:
      Neurochemical Characterization and Physiological Effects.
AB  - Xanthurenic acid (XA), formed from 3-hydroxykynurenine (3-HK) in the kynurenine
      pathway of tryptophan degradation, may modulate glutamatergic neurotransmission
      by inhibiting the vesicular glutamate transporter and/or activating Group II
      metabotropic glutamate receptors. Here we examined the molecular and cellular
      mechanisms by which 3-HK controls the neosynthesis of XA in rat, mouse and human
      brain, and compared the physiological actions of 3-HK and XA in the rat brain. In
      tissue homogenates, XA formation from 3-HK was observed in all three species and
      traced to a major role of kynurenine aminotransferase II (KAT II). Transamination
      of 3-HK to XA was also demonstrated using human recombinant KAT II. Neosynthesis
      of XA was significantly increased in the quinolinate-lesioned rat striatum,
      indicating a non-neuronal localization of the process. Studies using rat cortical
      slices revealed that newly produced XA is rapidly released into the extracellular
      compartment, and that XA biosynthesis can be manipulated experimentally in the
      same way as the production of kynurenic acid from kynurenine (omission of Na+ or
      glucose, depolarizing conditions, or addition of 2-oxoacids). The synthesis of XA
      from 3-HK was confirmed in vivo by striatal microdialysis. In slices from the rat
      hippocampus, both 3-HK and XA reduced the slopes of dentate gyrus field EPSPs.
      The effect of 3-HK was reduced in the presence of the KAT inhibitor
      aminooxyacetic acid. Finally, both 3-HK and XA reduced the power of gamma
      oscillatory activity recorded from the hippocampal CA3 region. Endogenous XA,
      newly formed from 3-HK, may therefore play a physiological role in attentional
      and cognitive processes.

PMID- 29031605
TI  - A waterborne outbreak of multiple diarrhoeagenic Escherichia coli infections
      associated with drinking water at a school camp.
AB  - BACKGROUND: In June 2015, a local public health laboratory was notified that
      students had developed gastroenteritis symptoms after attending a camp. An
      outbreak investigation was conducted to determine the extent and cause of the
      outbreak. METHOD: A retrospective cohort study was conducted to determine the
      correlations between the illness and specific exposures at the school camp. All
      attendees were interviewed with a standard questionnaire that addressed clinical
      symptoms, food consumption, and environmental exposures. Clinical specimens were
      cultured using standard microbiological methods for bacterial and viral
      pathogens. The genetic relationships of all isolates were determined using pulsed
      field gel electrophoresis (PFGE). RESULTS: A total 188 patients with symptoms of
      diarrhoea, abdominal pain, and nausea were identified. The completed
      questionnaires suggested that the consumption of drinking water was likely to be
      linked to this outbreak. Using microbiological methods, enterohaemorrhagic
      Escherichia coli, enteropathogenic E. coli, and enteroaggregative E. coli were
      isolated, and the isolates from both patient stool and environmental water
      samples displayed indistinguishable XbaI-PFGE patterns. The water system in the
      camp used groundwater drawn from a private underground reservoir for cooking and
      drinking. The environmental investigation revealed some problems with the water
      supply system, such as the use of inappropriate filters in the water purifier and
      a defect in the pipeline between the reservoir and the chlorination device.
      CONCLUSIONS: This outbreak points to the importance of drinking water quality
      management in group facilities where underground water is used and emphasizes the
      need for periodic sanitation and inspection to prevent possible waterborne
      outbreaks.

PMID- 29031606
TI  - An acute gastroenteritis outbreak caused by GII.P16-GII.2 norovirus associated
      with airborne transmission via the air conditioning unit in a kindergarten in
      Lianyungang, China.
AB  - Noroviruses are a common cause of acute gastroenteritis outbreaks in institutions
      including schools and kindergartens around the world. An outbreak caused by
      GII.P16-GII.2 norovirus in a kindergarten in Lianyungang, Jiangsu Province, China
      is reported here. An epidemiological investigation was conducted, and pathogen
      detection was performed. The descriptive analysis indicated that this outbreak in
      middle class 1 had a point source. Twenty cases of acute gastroenteritis occurred
      in this class within a period of 8.5h; the attack rate was 52.6% (20/38).
      Airborne transmission via the air conditioning unit in a confined restroom could
      have played a critical role in this outbreak. Sequence analysis of GII-positive
      samples confirmed that the norovirus GII.P16-GII.2 variant was the etiological
      agent of this outbreak.

PMID- 29031607
TI  - Hearing Without Neuroglobin.
AB  - Neuroglobin (Ngb) is a member of the globin family of respiratory proteins, which
      was recently observed in many neurons of the auditory pathways. Up to now,
      however, nothing was known about the role of Ngb in hearing processes. We
      therefore studied auditory function by recording distortion-product otoacoustic
      emissions (DPOAE) and auditory brainstem responses (ABRs) in wild-type (C57BL/6N)
      and Ngb-knockout mice. In KO mice, DPOAE thresholds were moderately augmented in
      the range of 5-18 kHz, reaching statistical significance at 8 and 10 kHz, while
      the ABR thresholds were not different between groups. The activation of the
      efferent system by an additional noise given to the contralateral ear resulted in
      an increased f2-f1-emission level only in WT animals. A noise exposure resulted
      in similar acute threshold shifts in the DPOAE and ABR of both animal groups. The
      recovery of hearing function, expressed by decreased DPOAE thresholds, was not
      significantly different between groups after four days and after four weeks. ABR
      recordings showed that threshold shifts elicited by noise-trauma were slightly
      better revised in wild-type mice. While ABR amplitudes were similar in both
      groups before noise overexposure, four weeks after trauma a moderate but
      statistically significant decrease of the latest peak-to-peak response amplitude
      (originating in the inferior colliculus) was observed in KO mice. Our results
      suggest that the lack of Ngb, at least in the model used in the present study,
      results in only marginal deficits in hearing ability. A putative functional role
      of Ngb in the efferent system warrants further studies.

PMID- 29031608
TI  - Steroidogenesis: Unanswered Questions.
AB  - Until the mid-1980s studies of steroidogenesis largely depended on identifying
      steroid structures and measuring steroid concentrations in body fluids. The
      molecular biology revolution radically revolutionized studies of steroidogenesis
      with the cloning of known steroidogenic enzymes, by identifying novel factors,
      and delineating the genetic basis of known and newly discovered diseases.
      Unfortunately, this dramatic success has led many young research-oriented
      endocrinologists to regard steroidogenesis as a 'solved area'. However, many
      important and exciting questions remain, especially concerning the mechanisms of
      cholesterol delivery to the steroidogenic machinery, the biochemistry of androgen
      synthesis, the regulation and biological role of adrenarche, fetal adrenal
      development and involution, the roles of steroids made in 'extraglandular' cells,
      and the search for genetic disorders. This review outlines some of these
      questions, but this list is necessarily incomplete.

PMID- 29031609
TI  - Multi-atlas-based segmentation of prostatic urethra from planning CT imaging to
      quantify dose distribution in prostate cancer radiotherapy.
AB  - BACKGROUND AND PURPOSE: Segmentation of intra-prostatic urethra for dose
      assessment from planning CT may help explaining urinary toxicity in prostate
      cancer radiotherapy. This work sought to: i) propose an automatic method for
      urethra segmentation in CT, ii) compare it with previously proposed surrogate
      models and iii) quantify the dose received by the urethra in patients treated
      with IMRT. MATERIALS AND METHODS: A weighted multi-atlas-based urethra
      segmentation method was devised from a training data set of 55 CT scans of
      patients receiving brachytherapy with visible urinary catheters. Leave-one-out
      cross validation was performed to quantify the error between the urethra
      segmentation and the catheter ground truth with two scores: the centerlines
      distance (CLD) and the percentage of centerline within a certain distance from
      the catheter (PWR). The segmentation method was then applied to a second test
      data set of 95 prostate cancer patients having received 78Gy IMRT to quantify
      dose to the urethra. RESULTS: Mean CLD was 3.25+/-1.2mm for the whole urethra and
      3.7+/-1.7mm, 2.52+/-1.5mm, and 3.01+/-1.7mm for the top, middle, and bottom
      thirds, respectively. In average, 53% of the segmented centerlines were within a
      radius<3.5mm from the centerline ground truth and 83% in a radius<5mm. The
      proposed method outperformed existing surrogate models. In IMRT, urethra DVH was
      significantly higher than prostate DVH from V74Gy to V79Gy. CONCLUSION: A multi
      atlas-based segmentation method was proposed enabling assessment of the dose
      within the prostatic urethra.

PMID- 29031610
TI  - Characteristics of 2.5 MV beam and imaging dose to patients.
AB  - PURPOSE: This work provides the beam characteristics and evaluates the imaging
      dose to patients for a 2.5 MV portal imaging beam. METHOD AND MATERIALS: The
      Monte Carlo technique has been used to simulate the 2.5 MV imaging beam. Beam
      characteristics have been analyzed including the energy spectra and the fluence
      distributions as a function of position away from the beam central axis. The
      accuracy of a simulated beam was validated through comparisons between the Monte
      Carlo calculated and measured dose distributions in a water phantom. The
      simulated 2.5 MV beam was also used to obtain the absorbed-dose beam quality
      conversion factor, kQ, for absorbed dose calibration. The simulated beams were
      then used to evaluate the imaging dose to patients compared with that from a
      conventional therapeutic 6 MV beam. RESULTS: The mean energies of photons and
      electrons in the 2.5 MV beam are 0.48 MeV and 0.37 MeV respectively. The photon
      fluence decreases at 20 cm away from the central axis by only up to 30% for this
      flattening-filter free beam. The values of %dd curves at depth = 10 cm are 53%
      and 63% for 10 * 10 cm2 and 40 * 40 cm2 fields respectively. Portal imaging doses
      (D50 of the DVHs) to the eyes, heart and bladder from representative pairs of 2.5
      MV (or 6 MV) setup images are 1.8 cGy (3.5 cGy), 1.1 cGy (2.5 cGy) and 1.0 cGy
      (2.4 cGy) for head, thorax and pelvis image acquisitions respectively.
      CONCLUSION: We provide dosimetric data, as well as estimates of organ imaging
      doses, for this 2.5 MV beam. When clinical default imaging protocols are used,
      the imaging dose from the 2.5 MV beam is about 50% of that from a 6 MV beam. The
      information can be used to select image procedures and to estimate organ dose
      from imaging procedures.

PMID- 29031611
TI  - Dose to mass for evaluation and optimization of lung cancer radiation therapy.
AB  - PURPOSE: To evaluate potential organ at risk dose-sparing by using dose-mass
      histogram (DMH) objective functions compared with dose-volume-histogram (DVH)
      objective functions. METHODS: Treatment plans were retrospectively optimized for
      10 locally advanced non-small cell lung cancer patients based on DVH and DMH
      objectives. DMH-objectives were the same as DVH objectives, but with mass
      replacing volume. Plans were normalized to dose to 95% of the PTV volume (PTV
      D95v) or mass (PTV-D95m). For a given optimized dose, DVH and DMH were
      intercompared to ascertain dose-to-volume vs. dose-to-mass differences.
      Additionally, the optimized doses were intercompared using DVH and DMH metrics to
      ascertain differences in optimized plans. Mean dose to volume, Dv?, mean dose to
      mass, DM?, and fluence maps were intercompared. RESULTS: For a given dose
      distribution, DVH and DMH differ by >5% in heterogeneous structures. In
      homogeneous structures including heart and spinal cord, DVH and DMH are nearly
      equivalent. At fixed PTV-D95v, DMH-optimization did not significantly reduce dose
      to OARs but reduced PTV-Dv? by 0.20+/-0.2Gy (p=0.02) and PTV-DM? by 0.23+/-0.3Gy
      (p=0.02). Plans normalized to PTV-D95m also result in minor PTV dose reductions
      and esophageal dose sparing (Dv? reduced 0.45+/-0.5Gy, p=0.02 and DM? reduced
      0.44+/-0.5Gy, p=0.02) compared to DVH-optimized plans. Optimized fluence map
      comparisons indicate that DMH optimization reduces dose in the periphery of lung
      PTVs. CONCLUSIONS: DVH- and DMH-dose indices differ by >5% in lung and lung
      target volumes for fixed dose distributions, but optimizing DMH did not reduce
      dose to OARs. The primary difference observed in DVH- and DMH-optimized plans
      were variations in fluence to the periphery of lung target PTVs, where low
      density lung surrounds tumor.

PMID- 29031612
TI  - Variants at HLA-A, HLA-C, and HLA-DQB1 Confer Risk of Psoriasis Vulgaris in
      Japanese.
AB  - Psoriasis vulgaris (PsV) is an autoimmune disease of skin and joints with
      heterogeneity in epidemiologic and genetic landscapes of global populations. We
      conducted an initial genome-wide association study and a replication study of PsV
      in the Japanese population (606 PsV cases and 2,052 controls). We identified
      significant associations of the single nucleotide polymorphisms with PsV risk at
      TNFAIP3-interacting protein 1and the major histocompatibility complex region (P =
      3.7 * 10-10 and 6.6 * 10-15, respectively). By updating the HLA imputation
      reference panel of Japanese (n = 908) to expand HLA gene coverage, we fine-mapped
      the HLA variants associated with PsV risk. Although we confirmed the PsV risk of
      HLA-C*06:02 (odds ratio = 6.36, P = 0.0015), its impact was relatively small
      compared with those in other populations due to rare allele frequency in Japanese
      (0.4% in controls). Alternatively, HLA-A*02:07, which corresponds to the cysteine
      residue at HLA-A amino acid position 99 (HLA-A Cys99), demonstrated the most
      significant association with PsV (odds ratio = 4.61, P = 1.2 * 10-10). In
      addition to HLA-A*02:07 and HLA-C*06:02, stepwise conditional analysis identified
      an independent PsV risk of HLA-DQbeta1 Asp57 (odds ratio = 2.19, P = 1.9 * 10-6).
      Our PsV genome-wide association study in Japanese highlighted the genetic
      architecture of PsV, including the identification of HLA risk variants.

PMID- 29031613
TI  - Pathogenic mutations of the human mitochondrial citrate carrier SLC25A1 lead to
      impaired citrate export required for lipid, dolichol, ubiquinone and sterol
      synthesis.
AB  - Missense mutations of the human mitochondrial citrate carrier, encoded by the
      SLC25A1 gene, lead to an autosomal recessive neurometabolic disorder
      characterised by neonatal-onset encephalopathy with severe muscular weakness,
      intractable seizures, respiratory distress, and lack of psychomotor development,
      often resulting in early death. Here, we have measured the effect of all twelve
      known pathogenic mutations on the transport activity. The results show that nine
      mutations abolish transport of citrate completely, whereas the other three reduce
      the transport rate by >70%, indicating that impaired citrate transport is the
      most likely primary cause of the disease. Some mutations may be detrimental to
      the structure of the carrier, whereas others may impair key functional elements,
      such as the substrate binding site and the salt bridge network on the matrix side
      of the carrier. To understand the consequences of impaired citrate transport on
      metabolism, the substrate specificity was also determined, showing that the human
      citrate carrier predominantly transports citrate, isocitrate, cis-aconitate,
      phosphoenolpyruvate and malate. Although D-2- and L-2 hydroxyglutaric aciduria is
      a metabolic hallmark of the disease, it is unlikely that the citrate carrier
      plays a significant role in the removal of hydroxyglutarate from the cytosol for
      oxidation to oxoglutarate in the mitochondrial matrix. In contrast, computer
      simulations of central metabolism predict that the export of citrate from the
      mitochondrion cannot be fully compensated by other pathways, restricting the
      cytosolic production of acetyl-CoA that is required for the synthesis of lipids,
      sterols, dolichols and ubiquinone, which in turn explains the severe disease
      phenotypes.

PMID- 29031614
TI  - High Mobility Group Box 1 is a novel pathogenic factor and a mechanistic
      biomarker for epilepsy.
AB  - Approximately 30% of epilepsy patients experience seizures that are not
      controlled by the available drugs. Moreover, these drugs provide mainly a
      symptomatic treatment since they do not interfere with the disease's mechanisms.
      A mechanistic approach to the discovery of key pathogenic brain modifications
      causing seizure onset, recurrence and progression is instrumental for designing
      novel and rationale therapeutic interventions that could modify the disease
      course or prevent its development. In this regard, increasing evidence shows that
      neuroinflammation is a pathogenic factor in drug-resistant epilepsies. The High
      Mobility Group Box 1 (HMGB1)/Toll-like receptor 4 axis is a key initiator of
      neuroinflammation following brain injuries leading to epilepsy, and its
      activation contributes to seizure mechanisms in animal models. Recent findings
      have shown dynamic changes in HMGB1 and its isoforms in the brain and blood of
      animals exposed to acute brain injuries and undergoing epileptogenesis, and in
      surgically resected epileptic foci in humans. HMGB1 isoforms reflect different
      pathophysiological processes, and the disulfide isoform, which is generated in
      the brain during oxidative stress, is implicated in seizures, cell loss and
      cognitive dysfunctions. Interfering with disulfide HMGB1-activated cell signaling
      mediates significant therapeutic effects in epilepsy models. Moreover, both
      clinical and experimental data suggest that HMGB1 isoforms may serve as
      mechanistic biomarkers for epileptogenesis and drug-resistant epilepsy. These
      novel findings suggest that the HMGB1 system could be targeted to prevent seizure
      generation and may provide clinically useful prognostic biomarkers which may also
      predict the patient's response to therapy.

PMID- 29031615
TI  - The leukotriene receptor antagonist pranlukast attenuates airway remodeling by
      suppressing TGF-beta signaling.
AB  - BACKGROUND/OBJECTIVE: Asthma is a chronic airway disease characterized by airway
      eosinophilic inflammation and remodeling, which are associated with a loss in
      lung function. Although both contribute significantly to asthma pathogenesis,
      mechanistic studies and drug discovery have focused on inflammatory targets. In
      this study, we investigated the effect of the leukotriene receptor antagonist
      pranlukast on allergic airway inflammation and remodeling in vivo and in vitro.
      METHOD: Four groups of female BALB/c mice (control; ovalbumin [OVA]-sensitized
      and -challenged; dimethyl sulfoxide [DMSO]-treated OVA; and pranlukast-treated
      OVA) were examined. Lung pathology, cytokine production, and airway
      hyperresponsiveness (AHR) measurements were compared among these groups. A human
      fetal lung fibroblast HFL-1 cell line was used in the peribranchial fibrosis
      analysis. RESULTS: OVA-sensitized and -challenged mice exhibited allergic airway
      inflammation and significant increases in Th2 cytokines. Pranlukast-treated mice
      showed significant attenuation of allergic airway inflammation. The pranlukast
      treatment decreased AHR and attenuated airway remodeling to goblet cell
      hyperplasia, collagen deposition, alpha-smooth muscle actin expression, and pro
      fibrotic gene expression. We further demonstrated that pranlukast not only
      inhibited transforming growth factor-beta 1 (TGF-beta1)-induced Smad signaling in
      human fetal lung fibroblast cells but also simultaneously reduced collagen
      synthesis and pro-fibrotic gene expression. CONCLUSIONS: The leukotriene receptor
      antagonist pranlukast can reduce airway inflammation and remodeling by inhibiting
      TGF-beta/Smad signaling in an OVA-sensitized and -challenged asthma mouse model,
      thus suppressing AHR.

PMID- 29031616
TI  - Factors affecting the selection of an inhaler device for COPD and the ideal
      device for different patient profiles. Results of EPOCA Delphi consensus.
AB  - BACKGROUND: This study aimed to identify the relevant factors for the choice of
      an inhaler device by physicians and the selection of the most important
      characteristics of a device according to different characteristics of patients
      with COPD. METHOD: In this two-round Delphi survey, 96 Spanish COPD-expert
      pulmonologists completed an internet-based, self-administered questionnaire,
      which consisted of a first part with 19 items related to the prioritization of
      the drug or the device, the experience, ability and preference of the patient,
      and the experience and preferences of the healthcare professional. For each item,
      responses were grouped into three categories based on a 9-point Likert-type
      scale, calculating the response frequency and the degree of consensus. The second
      part included 18 items related to the inhalation devices with the aim to identify
      the main characteristics of a device for 8 different profiles of patients with
      COPD. RESULTS: Experts considered that the selection of a device was relevant
      when choosing the treatment for COPD patients, although 62.5% of them prioritised
      the selection of the drug over the device. The experience of the patient (89.6%)
      and his/her ability to handle the device (97.9%), together with coordination
      (96.9%), ability to learn (87.5%) and adherence to therapy (84.4%) were the main
      aspects considered in the selection of inhalation device. The panel identified
      Respimat(r) as the most adequate device for patients with either low inspiratory
      flow or severely impaired lung function and Spiromax(r) for patients with either
      impaired fine motor skills or older than 70 years. CONCLUSIONS: Selection of the
      inhalation device is recognized by specialists as a strategic therapeutic
      decision and should be based on the characteristics of the individual patient.
      Some devices may be more adequate for different patient profiles.

PMID- 29031617
TI  - Steroid sparing effects of doxofylline.
AB  - Glucocorticosteroids are widely used in the treatment of asthma and chronic
      obstructive pulmonary disease (COPD). However, there are growing concerns about
      the side effect profile of this class of drug, particularly an increased risk of
      pneumonia. Over the last two decades there have been many attempts to find drugs
      to allow a reduction of glucocorticosteroids, including xanthines such as
      theophylline. Use of xanthines has been shown to lead to a reduction in the
      requirement for glucocorticosteroids, although xanthines also have a narrow
      therapeutic window limiting their wider use. Doxofylline is another xanthine that
      has been shown to be of clinical benefit in patients with asthma or COPD, but to
      have a wider therapeutic window than theophylline. In the present study we have
      demonstrated that doxofylline produces a clear steroid sparing effect in both an
      allergic and a non-allergic model of lung inflammation. Thus, we have shown that
      concomitant treatment with a low dose of doxofylline and a low dose of the
      glucocorticosteroid dexamethasone (that alone had no effect) significantly
      reduced both allergen-induced eosinophil infiltration into the lungs of allergic
      mice, and lipopolysaccharide (LPS)-induced neutrophil infiltration into the lung,
      equivalent to a higher dose of each drug. Our results suggest that doxofylline
      demonstrates significant anti-inflammatory activity in the lung which can result
      in significant steroid sparing activity.

PMID- 29031618
TI  - Characterization of the inhibitory activity of natural tanshinones from Salvia
      miltiorrhiza roots on protein tyrosine phosphatase 1B.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator that plays an
      important role in many signaling pathways, especially those associated with
      insulin resistance. In this study, we investigated the anti-diabetic potential of
      12 natural tanshinones isolated from Salvia miltiorrhiza (S. miltiorrhiza) Bunge
      (Lamiaceae), deoxyneocryptotanshinone (1), grandifolia F (2), ferruginol (3),
      cryptotanshinone (4), tanshinone IIA (5), tanshinol B (6), tanshinone IIB (7),
      tanshinonal (8), methyl tanshinonate (9), 15,16-dihydrotanshinone I (10),
      tanshinone I (11), and dehydrodanshenol A (12) and evaluated their inhibitory
      activity against PTP1B. Tanshinones 4, 6 and 12 exhibited potent PTP1B inhibitory
      activity with IC50 values of 5.5 +/- 0.9, 4.7 +/- 0.4 and 8.5 +/- 0.5 MUM,
      respectively. In addition, tanshinones 1-3, 5 and 7-11 showed promising dose
      dependent inhibition of PTP1B over IC50 values ranging from 18.6 to 254.8 MUM.
      Enzyme kinetic analysis of PTP1B inhibition revealed that 4 and 6 were mixed 
      noncompetitive type inhibitors, whereas 12 was a classical-noncompetitive type
      inhibitor. Furthermore, 4, 6 and 12 were docked with the PTP1B enzyme using
      molecular docking simulations (AutoDock 4.2) and exhibited negative binding
      energy (-6.4 to -8.7 kcal/mol), indicating high binding affinity to PTP1B active
      site residues. Structure-activity relationships (SAR) analysis revealed that
      structural modifications of ring A and furan or dihydrofuran ring D on the basic
      structure of tanshinones influenced their activity. Overall, results indicated
      that tanshinones from S. miltiorrhiza are potential anti-diabetic candidates that
      should be explored in the development of preventive and therapeutic modalities
      for the treatment of diabetes as well as diabetes-associated complications.

PMID- 29031619
TI  - Chemoprevention by artesunate in a preclinical model of colorectal cancer
      involves down regulation of beta-catenin, suppression of angiogenesis, cellular
      proliferation and induction of apoptosis.
AB  - Use of anti-inflammatory drugs is well known to decrease the risk of colorectal
      cancer, one of the most common causes of cancer related mortality. In view of
      anti-inflammatory property of artesunate reported in various experimental models,
      the present study was carried out to evaluate its efficacy in rat model where
      colon carcinogenesis was induced by 1, 2 dimethylhydrazine (DMH). A time course
      study revealed that two injections of DMH given at an interval of one week
      resulted in appearance of multiple plaque lesions and aberrant crypt foci in the
      colon with a peak effect occurring at the end of 8 weeks. An efficacy study
      carried out with daily oral administration of artesunate (50 and 150 mg/kg) and
      aspirin (60 mg/kg) showed a marked reduction in pre-neoplastic changes with a
      significant decrease in the number of aberrant crypt foci, crypt multiplicity and
      restoration of histoarchitecture. Both the drugs down regulated beta-catenin
      signaling, reduced the levels of angiogenic markers like VEGF, MMP-9 and
      inhibited cellular proliferation. The anti-cancer effect of these drugs was
      concomitant with the pro-apoptotic effect as revealed by increased DNA
      fragmentation, TUNEL positivity and Bax/Bcl2 immunoreactivity. This is the first
      study to evaluate the inhibitory effect of artesunate on pre-neoplastic changes
      in colon where its chemopreventive effect was found to be comparable to that of
      aspirin. Our study strengthens the previous findings and shows that it has a
      preventive and therapeutic potential in the treatment of colon cancer.

PMID- 29031620
TI  - Targeting non-small cell lung cancer with small-molecule EGFR tyrosine kinase
      inhibitors.
AB  - Epidermal growth factor (EGFR) tyrosine kinase inhibitors (TKIs), such as
      gefitinib and erlotinib, show excellent clinical efficacy for patients with non
      small cell lung cancer (NSCLC) with EGFR mutations, including Exon 19 deletion
      and single-point substitution, and L858R of exon 21. The reason for the reduction
      in effectiveness of these EGFR TKIs is the T790M gatekeeper mutation in the ATP
      binding pocket of Exon 20, which increases the affinity of EGFR for ATP. Newer
      EGFR TKIs, such as afatinib, osimertinib, rociletinib, EGF816 and ASP8273,
      selectively target T790M mutants, sparing wild-type EGFR. EGFR TKIs have fewer
      adverse effects than chemotherapy and also improve progression-free survival.
      Combination therapy of EGFR TKIs with anti-EGFR antibodies is recommended for
      overcoming the problem of resistance to some extent. This review could help
      medicinal chemists to design novel EGFR TKIs against NSCLC.

PMID- 29031621
TI  - Medicinal chemistry in drug discovery in big pharma: past, present and future.
AB  - The changes in synthetic and medicinal chemistry and related drug discovery
      science as practiced in big pharma over the past few decades are described. These
      have been predominantly driven by wider changes in society namely the computer,
      internet and globalisation. Thoughts about the future of medicinal chemistry are
      also discussed including sharing the risks and costs of drug discovery and the
      future of outsourcing. The continuing impact of access to substantial computing
      power and big data, the use of algorithms in data analysis and drug design are
      also presented. The next generation of medicinal chemists will communicate in
      ways that reflect social media and the results of constantly being connected to
      each other and data.

PMID- 29031622
TI  - Haspin: a promising target for the design of inhibitors as potent anticancer
      drugs.
AB  - Protein kinases constitute a large group of enzymes in eukaryotes and have an
      important role in many cellular processes. Several of these proteins are active
      kinases, such as haploid germ cell-specific nuclear protein kinase (Haspin), an
      atypical eukaryotic protein kinase that lacks sequence similarity with other
      eukaryotic protein kinases. Haspin is a serine/threonine kinase that associates
      with chromosome and phosphorylates threonine 3 of histone 3 during mitosis.
      Haspin overexpression or deletion results in defective mitosis. It has been shown
      that Haspin inhibitors have potent anti-tumoral effects. Given that the only
      Haspin substrate is threonine 3 of histone 3, inhibition of Haspin might have
      fewer adverse effects compared with other anticancer agents. Here, we highlight
      the chemical structures and actions of currently known Haspin inhibitors.

PMID- 29031623
TI  - Molecular dynamics simulation strategies for designing carbon-nanotube-based
      targeted drug delivery.
AB  - The carbon nanotube (CNT)-based target-specific delivery of drugs, or other
      molecular cargo, has emerged as one of the most promising biomedical applications
      of nanotechnology. To achieve efficient CNT-based drug delivery, the interactions
      between the drug, CNT and biomolecular target need to be properly optimized.
      Recent advances in the computer-aided molecular design tools, in particular
      molecular dynamics (MD) simulation studies, offer an appropriate low-cost
      approach for such optimization. This review highlights the various potential MD
      approaches for the simulation of CNT interactions with cell membranes while
      emphasizing various methods of cellular internalization and toxicities of CNTs to
      build new strategies for designing rational CNT-based targeted drug delivery to
      circumvent the limitations associated with the various clinically available
      nonspecific therapeutic agents.

PMID- 29031624
TI  - Impact of timing of cardiac arrest during hospitalization on survival outcomes
      and subsequent length of stay.
AB  - BACKGROUND: In-hospital cardiac arrest (IHCA) is common and often fatal. However,
      the association between timing of cardiac arrest and likelihood of survival to
      discharge, neurological status, and subsequent hospital length of stay (LOS) is
      unknown. METHODS: Within the Get-With-The-Guidelines Resuscitation registry, we
      identified 175,904 patients between 2000 and 2014 with an IHCA. Time from
      admission to IHCA was categorized as <3, 3-7, or >7days from admission.
      Multivariable hierarchical logistic regression models examined the association
      between timing of IHCA and survival to discharge, and, among survivors, favorable
      neurological survival (cerebral performance category score of 1) and LOS after
      IHCA. RESULTS: Overall, 83,811 (47.6%) of IHCAs occurred <3days from admission,
      whereas 47,713 (27.1%) and 44,380 (25.5%) occurred between 3 and 7 and >7days
      from admission, respectively. Cardiac arrests occurring later during the
      hospitalization were associated with lower survival ([reference: <3days]; for 3
      7days: adjusted OR 0.93 [0.90-0.96]; for >7days: adjusted OR 0.89 [0.86-0.92];
      P<0.01) and favorable neurological survival ([reference: <3days]; for 3-7days:
      adjusted OR 0.83 [0.77-0.89], for >7days: adjusted OR 0.55 [0.51-0.59]; P<0.01).
      Among survivors, later timing of IHCA was associated with longer subsequent LOS
      ([reference: <3days]; for 3-7days: 2.7 additional days [2.2-3.2]; for >7days: 6.8
      additional days [6.3-7.3]; P<0.001). CONCLUSION: Most IHCA occur after 3
      hospitalization days. Patients with IHCA after 3 hospital days had lower rates of
      survival to discharge, and, among survivors, lower rates of favorable
      neurological survival and longer duration of hospitalization from the time of
      cardiac arrest.

PMID- 29031625
TI  - Ideal (i) CPR: Looking beyond shadows in a cave.
AB  - Survival rates after cardiac arrest have shown minimal improvement in the last 60
      years. However, in some forward-thinking cities and hospitals, out-of and in
      hospital cardiac arrest survival rates exceed 20% and 40% respectively. These
      beacons of hope can enlighten us, providing a clearer vision of what it takes to
      provide Ideal cardiopulmonary resuscitation. To make progress in a field that has
      seemingly stagnated for too many decades, we must be open to new ideas and
      develop bundles of care that work in communities with varying EMS systems and
      various existing infrastructure to bring the best practices to the rest of the
      country.

PMID- 29031626
TI  - A better understanding of lay providers' CPR performance during resuscitation of
      out-of-hospital cardiac arrest.

PMID- 29031627
TI  - Development of a SYBR green-based real-time quantitative PCR assay to detect PCV3
      in pigs.
AB  - Porcine circovirus 3 (PCV3) has been reported in cases of porcine dermatitis and
      nephropathy syndrome, reproductive failure, cardiac and multi-systemic
      inflammation. A SYBR green-based real-time quantitative PCR (qPCR) assay was
      established in this study to detect PCV3 in 203 clinical samples from suckling
      piglets affected by congenital tremors in China. The limit of detection (LOD) of
      PCV3 was 1.73*104 copies/MUL for gel electrophoresis and 1.73*102 copies/MUL for
      SYBR green-based real-time qPCR. The melt curve analysis showed a single melt
      peak at 82.5 degrees C.The intra-assay coefficient of variation was up to 1.83%
      and the inter-assay coefficient of variation was up to 2.27%. The PCV3 positive
      detection rate of 203 clinical samples for the SYBR green-based real-time qPCR
      and the conventional PCR was 86.70% (176/203) and 26.60% (54/203), respectively.
      Each tissue detected in the SYBR green-based real-time qPCR showed a higher
      positive rate than that detected in the conventional PCR. These results indicated
      that the SYBR green-based real-time qPCR assay is a powerful method with high
      sensitivity, specificity and reproducibility for epidemiological investigations
      of PCV3.

PMID- 29031628
TI  - Ultrasound and the Complete Urologist Part 1: Methodology.
AB  - Computed tomography (CT) scanning is considered as the imaging study of choice
      for asymptomatic microhematuria according to the American Urological Association
      guidelines. For those patients with persistence of microhematuria after a
      negative initial examination, the guidelines suggest repeating the evaluation
      including CT scanning within 3 to 5 years. However, the cost and risk involved
      for utilizing this technology going forward is an issue, especially when the
      yield of finding significant pathology on subsequent imaging studies is
      exceedingly low. To minimize those concerns, I have proposed incorporating the
      utilization of ultrasound rather than the guideline-recommended CT for reasons
      and considerations to be discussed. In addition, I propose extending the use of
      ultrasound beyond evaluation of asymptomatic microhematuria to the routine
      urologic physical examination as it is superior to the current standard of
      palpation and percussion. The original concept of applying sound to a physical
      examination led to the technique of percussion. Technological advancement has
      taken the same sound, converted it to a digital image, and allowed us to see what
      we hear to achieve a greater diagnostic accuracy. The literature on this subject
      is reviewed and demonstrates support for just such a change in the delivery of
      urologic healthcare. I conclude by proposing that the quality of urologic care
      can be enhanced during a routine urologic physical examination through upgrading
      the technique of palpation and percussion by routinely utilizing ultrasound,
      creating the Complete Urologist.

PMID- 29031629
TI  - Ultrasound and the Complete Urologist Part 2: Outcomes.
AB  - Outcome studies help establish the benefits of tests or procedures that can
      change the delivery of medical care. Through this discourse, the current status
      of outcomes with respect to the use of ultrasound imaging for AMH as well as its
      general use during a routine urologic physical examination are explored. The
      changes in today's health care environment focus on cost reduction and outcomes
      that produce value in the context of patient satisfaction. The question is
      whether we have to wait for outcome results (that can take a lengthy period of
      time to achieve) before the benefits produced by ultrasound can be applied. This
      report reviews the literature and the role ultrasound can play in today's
      urologic health care environment. Supportive evidence demonstrates the value that
      ultrasound use brings to the urologic examining table for AMH and to daily
      urologic practice to the benefit of both patient and physician.

PMID- 29031630
TI  - The ZtVf1 transcription factor regulates development and virulence in the foliar
      wheat pathogen Zymoseptoria tritici.
AB  - The dimorphic fungal pathogen, Zymoseptoria tritici undergoes discrete
      developmental changes to complete its life cycle on wheat. Molecular mechanisms
      underlying morphogenesis during infection process of Z. tritici are poorly
      understood. In this study, we have investigated the role of ZtVf1 gene encoding a
      transcription factor belonging to C2-H2 subfamily. In planta assays revealed that
      ZtVf1 is required for virulence. Reduced necrotic lesions and low pycnidia
      density within the lesions resulted in significantly reduced virulence of ZtVf1
      mutants. Cytological analysis showed that the impaired virulence of ZtVf1 mutants
      attributed to reduced penetration and colonization along with hampered pycnidia
      differentiation. In vitro phenotyping showed that ZtVf1 deletion affects hyphal
      branching and biomass production suggesting that the reduced tissue colonization
      by the ZtVf1 mutant might be due to lower hyphal branching and less fungal
      biomass production. In addition, the majority of infected substomatal cavities by
      the ZtVf1 mutant filled with compacted mycelia mat that did not differentiate to
      mature pycnidia indicating that the impaired melanization negatively affected
      pycnidia formation and maturation. The ZtVf1 might target multiple genes
      belonging to different cellular processes whose identification is of eminent
      interest to increase our understanding of this pathosystem. Overall, the data
      provided in this study indicates that attenuated pathogenicity of ZtVf1 mutant is
      due to involvement of this gene in the regulation of both early and late stages
      of infection.

PMID- 29031631
TI  - Most probable number with visual based LAMP for the quantification of reductive
      dehalogenase genes in groundwater samples.
AB  - The remediation of chlorinated solvent contaminated sites frequently involves
      bioaugmentation with mixed cultures containing Dehalococcoides mccartyi. Their
      activity is then examined by quantifying reductive dehalogenase (RDase) genes.
      Recently, we described a rapid, low cost approach, based on loop mediated
      isothermal amplification (LAMP), which allowed for the visual detection of RDase
      genes from groundwater. In that study, samples were concentrated (without DNA
      extraction), incubated in a water bath (avoiding the use of a thermal cycler) and
      amplification was visualized by the addition of SYBR green (post incubation).
      Despite having a detection limit less than the threshold recommended for
      effective remediation, the application of the assay was limited because of the
      semi-quantitative nature of the data. Moreover, the assay was prone to false
      positives due to the aerosolization of amplicons. In this study, deoxyuridine
      triphosphate (dUTP) and uracil DNA glycosylase (UNG) were incorporated into the
      assay to reduce the probability of false positives. Optimization experiments
      revealed a UNG concentration of 0.2units per reaction was adequate for degrading
      trace levels of AUGC based contamination (~1.4*104 gene copies/reaction) without
      significant changes to the detection limit (~100 gene copies/reaction).
      Additionally, the optimized assay was used with the most probable number (MPN)
      method to quantify RDase genes (vcrA and tceA) in multiple groundwater samples
      from a chlorinated solvent contaminated site. Using this approach, gene
      concentrations were significantly correlated to concentrations obtained using
      traditional methods (qPCR and DNA templates). Although the assay underestimated
      RDase genes concentrations, a strong correlation (R2=0.78 and 0.94) was observed
      between the two data sets. The regression equations obtained will be valuable to
      determine gene copies in groundwater using the newly developed, low cost and time
      saving method.

PMID- 29031632
TI  - Separate transcriptionally regulated pathways specify distinct classes of sister
      dendrites in a nociceptive neuron.
AB  - The dendritic processes of nociceptive neurons transduce external signals into
      neurochemical cues that alert the organism to potentially damaging stimuli. The
      receptive field for each sensory neuron is defined by its dendritic arbor, but
      the mechanisms that shape dendritic architecture are incompletely understood.
      Using the model nociceptor, the PVD neuron in C. elegans, we determined that two
      types of PVD lateral branches project along the dorsal/ventral axis to generate
      the PVD dendritic arbor: (1) Pioneer dendrites that adhere to the epidermis, and
      (2) Commissural dendrites that fasciculate with circumferential motor neuron
      processes. Previous reports have shown that the LIM homeodomain transcription
      factor MEC-3 is required for all higher order PVD branching and that one of its
      targets, the claudin-like membrane protein HPO-30, preferentially promotes
      outgrowth of pioneer branches. Here, we show that another MEC-3 target, the
      conserved TFIIA-like zinc finger transcription factor EGL-46, adopts the
      alternative role of specifying commissural dendrites. The known EGL-46 binding
      partner, the TEAD transcription factor EGL-44, is also required for PVD
      commissural branch outgrowth. Double mutants of hpo-30 and egl-44 show strong
      enhancement of the lateral branching defect with decreased numbers of both
      pioneer and commissural dendrites. Thus, HPO-30/Claudin and EGL-46/EGL-44
      function downstream of MEC-3 and in parallel acting pathways to direct outgrowth
      of two distinct classes of PVD dendritic branches.

PMID- 29031633
TI  - Translation of noncoding RNAs: Focus on lncRNAs, pri-miRNAs, and circRNAs.
AB  - Mammalian genome is pervasively transcribed, producing large number of noncoding
      RNAs (ncRNAs), including long noncoding RNAs (lncRNAs), primary miRNAs (pri
      miRNA), and circular RNAs (circRNAs). The translation of these ncRNAs has long
      been overlooked. Increasing studies, however, based on ribosome profiling in
      various organisms provide important clues to unanticipated translation potential
      of lncRNAs. Moreover, a few functional peptides encoded by lncRNAs and pri-miRNAs
      underline the significance of their translation. Recently, several novel
      researches also evidence the translation of endogenous circRNAs. Given the
      functional significance exemplified by peptides translated by some ncRNAs and
      their pervasive translation, it is not too far-fetched to image that abnormal
      translation of ncRNAs may contribute to human diseases. Through challenging,
      deciphering ncRNA translation is required for comprehensive understanding of
      biology and medicine. In this review, we firstly present evidence concerning
      translation potential of lncRNAs and go on to introduce a few functional short
      peptides encoded by lncRNAs. Then, salient observations showing translation of
      pri-miRNAs and circRNAs are described in detail. We end by discussing the impact
      of ncRNA translation beyond producing peptides and referring briefly to the
      potential role of abnormal ncRNA translation in human diseases.

PMID- 29031634
TI  - Fecal bacteria from treatment-naive Crohn's disease patients can skew helper T
      cell responses.
AB  - Many studies have demonstrated that the inflamed mucosa of Crohn's disease (CD)
      patients presented a disturbed gut commensal community, and the shift in
      microbial composition and species variety is associated with disease severity. To
      establish a link between changes in the intestinal bacterial composition and the
      alteration of inflammation, we obtained fecal bacteria from CD patients and non
      CD controls. The bacteria were then used to stimulate the peripheral blood
      mononuclear cells (PBMCs) from one non-CD individual. We found that the frequency
      of IFN-gamma- and IL-17-expressing CD4 T cells was significantly higher after
      stimulation with CD bacteria than with non-CD bacteria, while the frequency of IL
      4- and IL-10-expressing CD4 T cells was significantly decreased after stimulation
      with CD bacteria. A similar trend was observed in the level of cytokine
      expression and transcription expression. However, this difference was not clear
      cut, as overlapping regions were observed between the two groups. With longer
      stimulation using CD bacteria, the skewing toward Th1/Th17 responses were further
      increased. This increase depended on the presence of monocytes/macrophages.
      Interestingly, we also found that B cells presented an inhibitory effect in CD
      bacteria-mediated skewing toward Th1/Th17 cells and promoted IL-10 secretion in
      CD bacteria-stimulated PBMCs. Together, our results demonstrated that CD bacteria
      could promote Th1/Th17 inflammation in a host factor-independent fashion.

PMID- 29031635
TI  - Correlation of altered expression of a long non-coding RNA, NEAT1, in peripheral
      blood mononuclear cells with dengue disease progression.
AB  - The association of long non-coding RNAs (lncRNAs) with dengue disease progression
      is currently unknown. Therefore, the present study aimed to identify lncRNAs in
      different categories of dengue patients and evaluate their association with
      dengue disease progression. Herein, we examined the expression profiles of
      lncRNAs and protein-coding genes between other febrile illness (OFI) and
      different grade of dengue patients through high-throughput RNA sequencing. We
      identified Nuclear Enriched Abundant Transcript 1 (NEAT1) as one of the
      differentially expressed lncRNAs (adjusted P <= 0.05 and log-fold change >= 2)
      and subsequently validated the expression by qRT-PCR. The co-expression analysis
      further revealed that NEAT1 and the coding gene IFI27 were highly co-expressed
      and negatively correlated with dengue severity. Using regression analysis, we
      observed that NEAT1 expression was significantly dependent on disease progression
      (Coefficient = -0.27750, SE Coefficient = 0.07145, and t = -3.88).Further,
      receiver operating characteristic (ROC) curve revealed that NEAT1 expression
      could discriminate DI from DS (sensitivity and specificity of 100% (95%CI: 85.69 
      97.22) and area under the curve (AUC) = 0.97). Overall, the results of this
      study offer the first experimental evidence demonstrating the correlation between
      lncRNAs and severe dengue phenotype. Monitoring NEAT1and IFI27 expression in PBMC
      may be useful in understanding dengue virus-induced disease progression.

PMID- 29031636
TI  - Rotavirus vaccination takes seasonal signature of childhood diarrhea back to pre
      sanitation era in Brazil.
AB  - OBJECTIVES: This study aimed to examine the previously unknown long-term spatio
      temporal patterns in diarrheal morbidity and mortality across age groups and
      geography in Brazil under the light of evolving socioeconomic factors and
      interventions. METHODS: Nationwide mortality (1979-2014) and hospitalization
      (1998-2014) data were obtained from the Brazilian Ministry of Health. Analyses of
      long-term secular trends and seasonality of diarrheal morbidity and mortality
      were performed in EPIPOI (www.epipoi.info). RESULTS: For most states, the primary
      peak in mortality risk among children under 5 years occurred from December-April
      (summer/early autumn) from 1979-1988. From 2000-2005 (before the 2006
      implementation of rotavirus vaccination), the pattern switched to June-October
      (winter/early spring). By 2007-2014, the peak in mortality shifted back towards
      summer/early autumn. A similar pattern was observed for hospitalizations. These
      patterns were particularly apparent in non-equatorial regions of the country. In
      contrast, the risk of diarrhea-related death among older children (5-19 years)
      did not demonstrate well-defined seasonality or spatial patterns. CONCLUSIONS:
      Rotavirus vaccination policies were associated with a shift in the timing of
      seasonal peaks in children under 5, reminiscent of the summer diarrhea period
      common decades prior. Additionally, young children were shown to have distinct
      disease patterns compared to other age groups, suggesting different etiologies.

PMID- 29031637
TI  - Molecular epidemiology of multi- and extensively-drug-resistant Mycobacterium
      tuberculosis in Ireland, 2001-2014.
AB  - OBJECTIVES: The primary objective of this work was to examine the acquisition and
      spread of multi-drug resistant (MDR) tuberculosis (TB) in Ireland. METHODS: All
      available Mycobacterium tuberculosis complex (MTBC) isolates (n = 42), from MDR
      TB cases diagnosed in Ireland between 2001 and 2014, were analysed using
      phenotypic drug-susceptibility testing, Mycobacterial-Interspersed-Repetitive
      Units Variable-Number Tandem-Repeat (MIRU-VNTR) genotyping, and whole-genome
      sequencing (WGS). RESULTS: The lineage distribution of the MDR-TB isolates
      comprised 54.7% Euro-American, 33.3% East Asian, 7.2% East African Indian, and
      4.8% Indo-Oceanic. A significant association was identified between the East
      Asian Beijing sub-lineage and the relative risk of an isolate being MDR. Over 75%
      of MDR-TB cases were confirmed in non-Irish born individuals and 7 MIRU-VNTR
      genotypes were identical to clusters in other European countries indicating cross
      border spread of MDR-TB to Ireland. WGS data provided the first evidence in
      Ireland of in vivo microevolution of MTBC isolates from drug-susceptible to MDR,
      and from MDR to extensively-drug resistant (XDR). In addition, they found that
      the katG S315T isoniazid and rpoB S450L rifampicin resistance mutations were
      dominant across the different MTBC lineages. CONCLUSIONS: Our molecular
      epidemiological analyses identified the spread of MDR-TB to Ireland from other
      jurisdictions and its potential to evolve to XDR-TB.

PMID- 29031638
TI  - dbGAPs: A comprehensive database of genes and genetic markers associated with
      psoriasis and its subtypes.
AB  - Psoriasis is a systemic hyperproliferative inflammatory skin disorder, although
      rarely fatal but significantly reduces quality of life. Understanding the full
      genetic component of the disease association may provide insight into biological
      pathways as well as targets and biomarkers for diagnosis, prognosis and therapy.
      Studies related to psoriasis associated genes and genetic markers are scattered
      and not easily amendable to data-mining. To alleviate difficulties, we have
      developed dbGAPs an integrated knowledgebase representing a gateway to psoriasis
      associated genomic data. The database contains annotation for 202 manually
      curated genes associated with psoriasis and its subtypes with cross-references.
      Functional enrichment of these genes, in context of Gene Ontology and pathways,
      provide insight into their important role in psoriasis etiology and pathogenesis.
      The dbGAPs interface is enriched with an interactive search engine for data
      retrieval along with unique customized tools for Single Nucleotide Polymorphism
      (SNP)/indel detection and SNP/indel annotations. dbGAPs is accessible at
      http://www.bmicnip.in/dbgaps/.

PMID- 29031639
TI  - Oscillatory neural representations in the sensory thalamus predict neuropathic
      pain relief by deep brain stimulation.
AB  - OBJECTIVE: Understanding the function of sensory thalamic neural activity is
      essential for developing and improving interventions for neuropathic pain.
      However, there is a lack of investigation of the relationship between sensory
      thalamic oscillations and pain relief in patients with neuropathic pain. This
      study aims to identify the oscillatory neural characteristics correlated with
      pain relief induced by deep brain stimulation (DBS), and develop a quantitative
      model to predict pain relief by integrating characteristic measures of the neural
      oscillations. APPROACH: Measures of sensory thalamic local field potentials
      (LFPs) in thirteen patients with neuropathic pain were screened in three
      dimensional feature space according to the rhythm, balancing, and coupling neural
      behaviours, and correlated with pain relief. An integrated approach based on
      principal component analysis (PCA) and multiple regression analysis is proposed
      to integrate the multiple measures and provide a predictive model. MAIN RESULTS:
      This study reveals distinct thalamic rhythms of theta, alpha, high beta and high
      gamma oscillations correlating with pain relief. The balancing and coupling
      measures between these neural oscillations were also significantly correlated
      with pain relief. SIGNIFICANCE: The study enriches the series research on the
      function of thalamic neural oscillations in neuropathic pain and relief, and
      provides a quantitative approach for predicting pain relief by DBS using thalamic
      neural oscillations.

PMID- 29031640
TI  - The application of mesenchymal stem cells to treat thermal and radiation burns.
AB  - Mesenchymal stem cells (MSCs) have been developed for a number of indications due
      to their regenerative and anti-inflammatory phenotypes and their utility is
      enhanced by the fact that allogeneic transplant is feasible with this cell type.
      Animal studies and early human cases indicate that this has the potential to be
      an exciting new therapy for treating chronic non-healing wounds such as diabetic
      ulcers, burns and cutaneous radiation burns. This review will focus on the use of
      MSCs to treat thermal and radiation burns. Large, severe burns are difficult to
      treat and pose a major public health burden worldwide. They are characterized by
      an extensive loss of the outer protective barrier, delayed wound healing,
      increased oxidative stress and a heightened inflammatory state. The breakdown of
      the protective barrier results in increased susceptibility to fluid loss and
      bacterial sepsis. In the case of radiation burns, chronic inflammation can result
      in subsequent waves of tissue injury leading to skin breakdown and necrosis. The
      aim of this review is to summarize the current knowledge on MSCs in treating
      thermal and radiation burns along with the specific scope of characterizing the
      biologic function of MSCs that help enhance wound healing in these chronic
      injuries.

PMID- 29031641
TI  - Recovery of human Achilles tendon three-dimensional deformation following
      conditioning.
AB  - OBJECTIVES: The tendon conditioning effect is transient, but the time course of
      recovery from conditioning is not known. This study examined the time-course
      recovery of three-dimensional (3D) Achilles tendon (AT) deformation immediately
      following a standardised AT conditioning protocol. DESIGN: Randomised crossover.
      METHODS: Ten healthy male adults (age: 24+/-5 years; height: 175.8+/-4.1cm; body
      mass: 78.4+/-6.3kg) attended the laboratory on 6 occasions. ATs were scanned
      using freehand 3D ultrasound during a 50% maximal voluntary isometric contraction
      (MVIC) of the plantarflexors immediately prior to and following the conditioning
      protocol (10*25s plantarflexion contractions at 50% MVIC), and then at either 15,
      30, 60, 90 or 120min post-conditioning, randomised by session. RESULTS: Free AT
      longitudinal strain was significantly increased from 3.13+/-0.19% pre
      conditioning to 7.49+/-0.20% immediately post-conditioning and was accompanied by
      a corresponding reduction in free AT transverse strain from -5.35+/-0.48% to 
      10.16+/-0.49% (p<0.001). There were no significant differences in free AT
      longitudinal or transverse strains at 60min relative to 0min post-conditioning,
      or between pre-conditioning strains and strains measured at 2h (p>0.05).
      CONCLUSIONS: The free AT undergoes a creep response during conditioning which is
      recoverable within 2h following conditioning. Recovery from conditioning has the
      potential to be a source of error during in vivo measurement of AT mechanical
      properties. The time window in which the free AT longitudinal and transverse
      strains could be achieved without a large confounding effect of creep recovery is
      0-60min post-conditioning.

PMID- 29031642
TI  - The effect of oral contraceptive use on salivary testosterone concentrations and
      athlete performance during international field hockey matches.
AB  - OBJECTIVES: To investigate the effect of oral contraceptive (OC) use on salivary
      testosterone (sal-T) concentrations and performance-related statistics in
      international field hockey matches. DESIGN: A cohort observational study with
      repeated measures. METHODS: Twenty-three elite female athletes were monitored
      across four international field hockey matches over a nine-day period. Salivary T
      was assessed 45min before each match and several match performance statistics
      were collated; load (i.e. ratings of perceived exertion*playing time), video
      derived positive actions (PA) and negative actions (NA), plus coach and player
      ratings of performance. The sal-T and match performance profiles of OC (n=7) and
      Non-OC (n=16) players were compared and predictive relationships tested. RESULTS:
      Pre-match sal-T concentrations were 35% higher in the Non-OC than the OC group
      (p=0.001), representing a large effect size (ES) difference of 0.96. The OC and
      Non-OC groups did not differ on any performance statistic (p>=0.348) with ES
      differences from -0.22 to 0.11. Salivary T was positively related to the number
      of PA during match play (p=0.017). Additional linkage between sal-T and NA
      emerged, but with opposing slopes (p=0.008) in the OC (B=-1.783, p=0.030) and Non
      OC (B=0.692, p=0.127) groups. CONCLUSIONS: OC usage by elite women athletes was
      accompanied by lower sal-T concentrations, but the performance outputs of the OC
      and Non-OC groups were similar. This suggests that the T differences had no
      impact on match performance. On an individual (population-averaged) level, sal-T
      was associated with PA and NA during these matches, though the response curves
      predicting NA differed for OC and Non-OC athletes.

PMID- 29031643
TI  - Physical fitness and psychological health in overweight/obese children: A cross
      sectional study from the ActiveBrains project.
AB  - OBJECTIVES: To examine the associations of physical fitness (i.e.
      cardiorespiratory fitness, muscular strength, and speed/agility) with
      psychological distress and psychological well-being in overweight/obese pre
      adolescent children. DESIGN: 110 overweight/obese children (10.0+/-1.1years old,
      61 boys) from the ActiveBrains project (http://profith.ugr.es/activebrains)
      participated in this cross-sectional study. METHODS: Physical fitness was
      evaluated by the ALPHA battery test. Cardiorespiratory fitness was additionally
      evaluated by a maximal incremental treadmill. Stress was assessed by the
      Children's Daily Stress Inventory, anxiety by the State-Trait Anxiety Inventory,
      depression by the Children Depression Inventory, positive affect and negative
      affect by the Positive and Negative Affect Scale for Children, happiness by the
      Subjective Happiness Scale, optimism by the Life Orientation Test, and self
      esteem by the Rosenberg Self-Esteem questionnaire. Linear regression adjusted for
      sex and peak height velocity was used to examine associations. RESULTS: Absolute
      upper-body muscular strength was negatively associated with stress and negative
      affect (beta=-0.246, p=0.047; beta=-0.329, p=0.010, respectively). Furthermore,
      absolute lower-body muscular strength was negatively associated with negative
      affect (beta=-0.301, p=0.029). Cardiorespiratory fitness, expressed by the last
      completed lap, and relative upper-body muscular strength were positively
      associated with optimism (beta=0.220, p=0.042; beta=0.240, p=0.017,
      respectively). Finally, absolute upper-body muscular strength was positively
      associated with self-esteem (beta=0.362, p=0.003) independently of sex and weight
      status (p for interactions >0.3), and absolute lower-body muscular strength was
      also positively associated with self-esteem (beta=0.352, p=0.008). CONCLUSIONS:
      Muscular strength was associated with psychological distress (i.e. stress and
      negative affect) and psychological well-being (i.e. optimism and self-esteem) as
      well as cardiorespiratory fitness was associated with optimism. Therefore,
      increased levels of physical fitness, specifically muscular strength, could have
      significant benefits for overweight/obese children psychological health.

PMID- 29031644
TI  - A preliminary evaluation of glial cell line-derived neurotrophic factor (GDNF)
      levels in cerebrospinal fluid across various gestational ages and clinical
      conditions of the neonate.
AB  - BACKGROUND: This study aims to investigate glial cell derived neurotrophic factor
      (GDNF) levels in newborns' umbilical cord blood and cerebrospinal fluid across
      various perinatal growth parameters and clinical conditions. METHODS: Cord blood
      from 20 newborns and 58 residual CSF samples (stored after completion of clinical
      testing) were collected. GDNF levels were determined using GDNF ELISA kits from
      R&D Systems in triplicates with appropriate controls to eliminate background.
      RESULTS: Cord blood GDNF levels were significantly higher (p=0.004) in preterm
      newborns (n=6) (115.05+/-57.17,pg/ml) when compared to term newborns (n=14)
      (19.67+/-10.67,pg/ml). GDNF levels in CSF trended (p=0.07) higher in term
      newborns (n=10) (19.56+/-9.11,pg/ml) when compared to preterm newborns at term or
      post term corrected gestational ages (n=5) (14.49+/-3.53,pg/ml). CONCLUSIONS:
      GDNF levels in preterm newborns were higher in cord blood and lower in CSF as
      compared to term newborns. It is important to further study circulating and CSF
      GDNF levels in newborns at different gestational ages and clinical conditions.

PMID- 29031646
TI  - International publication trends in dry eye disease research: A bibliometric
      analysis.
AB  - PURPOSE: To perform a bibliometric analysis in the field of dry eye disease (DED)
      research to characterize the current international status of DED research and to
      identify the most effective actors (journals, countries, authors) involved in
      this field. METHODS: Scientometric methods were used to evaluate global
      scientific production and development trends in DED research, using the Web of
      Science Core Collection. RESULTS: The growth of the literature related to DED
      averaged 12.18% over the last 10 years. A total of 5522 original and review
      articles, published in 821 different journals, were identified. The USA was the
      most productive country with 34.53% of the overall articles studied and 46.10% of
      the overall citations. The Ocular Surface published a very high percentage of
      articles related to DED relative to the total number of articles published
      (31.87%). The most productive institutions and the most frequently cited articles
      were from the USA and Japan. A network visualization map for country
      collaboration revealed that most European countries developed most of their
      collaborations with countries belonging to their own continent, which was not the
      case for the USA or Japan. A total of 41,956 KeyWords Plus were found with an
      average of 7.6 (SD = 3.15) KeyWords Plus per article. CONCLUSIONS: This study
      provides a broad view of the current status and trends in DED research and may
      help clinicians, researchers and policy makers better understand this research
      field and predict its dynamic directions.

PMID- 29031647
TI  - Barriers to antenatal psychosocial assessment and depression screening in private
      hospital settings.
AB  - PROBLEM: The evidence of benefit for antenatal psychosocial assessment and
      depression screening has been sufficient to lead the implementation of screening
      in public hospitals in all states of Australia. Details of the implementation of
      perinatal screening in private obstetric settings is less well known. AIM: As any
      successful implementation relies on the identification of local barriers, we
      aimed to determine what perceived or actual barriers may exist for the
      implementation of evidence-based perinatal screening interventions in private
      obstetric care, and specifically within small private hospitals. METHOD: The
      integrative literature review method offers a structured systematic approach to
      organise, synthesize and critique research from a range of sources. This method
      was used to determine what barriers have been identified in implementing
      psychosocial assessment and depression screening with women receiving obstetric
      care in private hospital settings. FINDINGS: The integrative review findings
      suggest that barriers to implementing psychosocial screening in the private
      sector are similar to those experienced in the public sector but may also be
      influenced by the corporate focus of private services. Barriers were identified
      among health professionals, within the personal and psychosocial context of women
      and their families, and at provider or system level. CONCLUSION: Once identified,
      barriers can be systematically addressed to enhance the success of implementing
      psychosocial and depression screening in the private sector. Screening is likely
      to be influenced by the business models and operating systems of private service
      providers. Health professionals working within this environment need more support
      to conduct perinatal assessment within this context.

PMID- 29031645
TI  - Neuropathic pain and dry eye.
AB  - Dry eye is a common, multifactorial disease currently diagnosed by a combination
      of symptoms and signs. Its epidemiology and clinical presentation have many
      similarities with neuropathic pain outside the eye. This review highlights the
      similarities between dry eye and neuropathic pain, focusing on clinical features,
      somatosensory function, and underlying pathophysiology. Implications of these
      similarities on the diagnosis and treatment of dry eye are discussed.

PMID- 29031648
TI  - A historical account of the governance of midwifery education in Australia and
      the evolution of the Continuity of Care Experience.
AB  - BACKGROUND: Midwifery programs leading to registration as a midwife in Australia
      have undergone significant change over the last 20 years. During this time
      accreditation and governance around midwifery education has been reviewed and
      refined, moving from state to national jurisdiction. A major change has been the
      mandated inclusion of Continuity of Care Experiences as a clinical practice-based
      learning component. AIM: The purpose of this discussion is to present the history
      of the governance and accreditation of Australian midwifery programs. With a
      particular focus on the evolution of the Continuity of Care Experience as a now
      mandated clinical practice based experience. METHODS: Historical and contemporary
      documents, research and grey literature, are drawn together to provide a
      historical account of midwifery programs in Australia. This will form the
      background to the inclusion of the Continuity of Care Experience and discuss
      research requirements to enhance the model to ensure it is educationally sound.
      DISCUSSION: The structure and processes for the Continuity of Care Experience
      vary between universities and there is currently no standard format across
      Australia. As such, how it is interpreted and conducted varies amongst students,
      childbearing women, academics and midwives. The Continuity of Care Experience has
      always been strongly advocated for; however there is scant evidence available in
      terms of its educational theory underpinnings. CONCLUSION: Research concerned
      with the intended learning objectives and outcomes for the Continuity of Care
      Experience will support the learning model and ensure it continues into the
      future as an educationally sound learning experience for midwifery students.

PMID- 29031649
TI  - [The 2015-2016 influenza epidemic: Late onset, clinical severity and emergence of
      the B Victoria virus].

PMID- 29031650
TI  - Tigecycline-based prolonged salvage therapy in patients presenting with complex
      bone and joint infection.
AB  - OBJECTIVES: To assess the clinical experience of tigecycline-based salvage
      therapy in patients presenting with Bone and Joint Infections (BJI). PATIENTS AND
      METHODS: Multicenter retrospective cohort study in France and Turkey (2007-2014).
      RESULTS: Thirty-six patients (age 58.2+/-17.8 years; 21 men) were included. The
      most frequently isolated bacteria were Enterobacteriaceae and staphylococci.
      Tigecycline (50mg BID, mainly in combination (69.4%), mean duration of 58 days)
      was indicated for multidrug resistance (90.6%) and/or previous antibiotic
      intolerance (36.1%), and/or as second- or third-line therapy (69.4%). Six
      patients (16.7%) experienced early treatment discontinuation for adverse event (4
      severe vomiting, 1 pancreatitis, 1 asymptomatic lipase increase). Clinical
      success was observed in 23 of 30 assessable patients who completed the
      tigecycline therapy (mean follow-up: 54.1+/-57.7 weeks). CONCLUSION: Prolonged
      tigecycline-based therapy could be an alternative in patients presenting with BJI
      requiring salvage therapy, especially if multidrug-resistant Enterobacteriaceae
      and/or staphylococci are involved.

PMID- 29031651
TI  - Vaccine criticism: Presence and arguments on French-speaking websites.
AB  - OBJECTIVE: To evaluate the presence of vaccine criticism on the French Web and to
      analyze strategies and arguments used by opponents of vaccination. METHODS: The
      most frequently used keywords associated with the terms "vaccination" and
      "vaccine" on Google.fr in September 2013 were identified and searched for
      individually on Google.fr. The links presented in the first three pages of
      results were reviewed to identify the most frequent providers of information. The
      proportion of critical content was determined by website type and a content
      analysis was performed. RESULTS: The main preoccupations about vaccination were
      general concerns; <1% of searches were guided by negative keywords. Institutional
      websites, healthcare websites, news websites and anti-vaccine websites were the
      most frequent providers of results. The proportion of anti-vaccine websites among
      the results was 11% for a neutral search and 24% for a search guided by negative
      keywords. Critical content was observed in other types of website. Six major
      strategies and categories of arguments used by opponents of vaccination were
      identified: the manipulation of science, the use of shocking images and an appeal
      to emotions via testimonies, a general vaccination conspiracy, the individual's
      freedom of choice not respected, an unnatural act and a negative benefit/risk
      balance. CONCLUSION: It seems important to monitor online vaccination debates, to
      develop an institutional presence that meets the needs of Internet users and to
      help them develop a critical view.

PMID- 29031652
TI  - [Scedosporium apiospermum skin infection mimicking a pyoderma gangrenosum].

PMID- 29031653
TI  - Discussion of: "Operative versus non-operative management in the care of patients
      with complicated appendicitis".

PMID- 29031654
TI  - Discussion of: "Disparate effects of catecholamines under stress conditions on
      endothelial glycocalyx injury: An in vitro model".

PMID- 29031655
TI  - Discussion of: "Is routine head CT indicated in awake stable older patients after
      a ground level fall?"

PMID- 29031656
TI  - Disparities in incidence of early- and late-onset colorectal cancer between
      Hispanics and Whites: A 10-year SEER database study.

PMID- 29031657
TI  - Achyrocline alata potentiates repair of skin full thickness excision in mice.
AB  - Plants of the Asteraceae family have been traditionally used as medicinal plants.
      The species Achyrocline satureioides and Achyrocline alata present anti
      inflammatory properties and great chemical similarity. However, no study has been
      performed to evaluate the influence of these plants on skin wound healing in
      vivo. Here, we have assessed the effect of these plants extracts on skin wound
      healing in mice. Mice were randomly arranged into three groups (n = 10), an
      injury was performed on the dorsal area of the animals, which received the
      following topical treatment: group 1, control (ointment base); group 2, A.
      satureioides extract; group 3, A. alata extract. The solution for treatment was
      prepared as 10% (w/w) concentration. The wound area was measured on days 1, 4, 9,
      15 and 17 after treatment and tissues of local lesion were collected on the ninth
      day for histological analysis. A. alata was more effective since it induced
      earlier wound closure associated with decreasing initial inflammatory response,
      faster reepithelialization and collagen remodeling. A. satureioides improved the
      collagen renovation, but induced slower closure, which may be due to different
      concentrations of phenolic compounds among the plants here studied. Both plants
      did not alter the ultrastructural characteristics of cells in the healing
      process. In conclusion, our findings suggest the potent wound healing capacity of
      A. alata extracts, as demonstrated by more efficient and faster induction of
      wound closure. We believe this plant is a potential wound healing treatment for
      humans and further studies are necessary to assess its clinical practice.

PMID- 29031658
TI  - Randomized controlled pilot study of the preoperative use of brimonidine 0.33%
      topical gel for hemostasis in Mohs micrographic surgery.
AB  - BACKGROUND: Brimonidine topical gel may be useful in cutaneous surgical
      procedures because of its vasoconstricting properties. OBJECTIVE: Assess the
      hemostatic effect of topically applied brimonidine in patients being treated with
      anticoagulants and undergoing Mohs micrographic surgery (MMS). METHODS: Subjects
      undergoing MMS were randomly assigned to the control (n = 10) or study arm (n =
      14). Controls received standard-of-care MMS, whereas the study arm received the
      same and preoperative application of brimonidine. Evaluations included rate of
      blood flow, percentage of wound bed surface area needing electrocautery, and
      changes in skin colorimeter readings. RESULTS: The treatment arm had 68% less
      blood loss over 30 seconds versus the control arm (P < .05). No patient in the
      brimonidine arm had more than 50% of the wound bed cauterized versus 80% in the
      controls. Erythema in the treatment arm was decreased by 3.89 times (P < .01)
      versus in the control arm. LIMITATIONS: Limitations were small sample size; sites
      limited to the face; the fact that measurement of bleeding did not account for
      anesthetic mixed with blood; visual estimation of percentage of wound surface
      area requiring cauterization; and no measurement of volume of anesthesia, wound
      depth, or postoperative complications. CONCLUSION: Preoperative application of
      brimonidine 0.33% gel may help decrease blood loss and the need for
      electrocautery during MMS for patients taking anticoagulants.

PMID- 29031659
TI  - Validity of skin cancer malignancy reporting to the Organ Procurement Transplant
      Network: A cohort study.
AB  - BACKGROUND: The Organ Procurement Transplant Network (OPTN) registry collects
      data on posttransplant malignancies in solid organ transplant recipients.
      Complete and accurate registry data on skin cancer is critical for research on
      epidemiology and interventions. OBJECTIVE: The study goal was to determine the
      validity of Organ Procurement Transplant Network skin cancer data. METHODS: This
      cohort study compared reporting of posttransplant squamous cell carcinoma (SCC)
      and malignant melanoma (MM) in OPTN to medical-record review-derived data from
      the Transplant Skin Cancer Network (TSCN) database. In total, 4934 organ
      transplant recipients from the TSCN database were linked to patient-level OPTN
      malignancy data. We calculated sensitivity, specificity, correct classification
      (CC), positive predictive value (PPV), and negative predictive value (NPV) for
      SCC and MM reporting in the OPTN database. RESULTS: OPTN reporting for SCC
      (population prevalence 11%) had sensitivity 41%, specificity 99%, PPV 88%, NPV
      93%, and CC 93%. OPTN reporting for MM (population prevalence 1%) had sensitivity
      22%, specificity 100%, PPV 73%, NPV 99%, and CC 99%. LIMITATIONS: Only a subset
      of patients in the TSCN cohort had matched United Network for Organ Sharing
      cancer registry data for comparison. CONCLUSION: OPTN reporting had poor
      sensitivity but excellent specificity for SCC and MM. Dermatologists and
      transplant physicians are encouraged to improve the validity of OPTN skin cancer
      data through improved communication and reporting.

PMID- 29031660
TI  - Lichen planus affecting the female genitalia: A retrospective review of patients
      at Mayo Clinic.
AB  - BACKGROUND: Genital or vulval lichen planus (VLP) may have a disabling effect on
      a patient's quality of life. Evidence-based management guidelines are lacking for
      VLP. OBJECTIVE: We sought to review clinical presentation and treatment of
      patients who received a diagnosis of VLP. METHODS: The 100 consecutive patients
      who received a diagnosis of VLP at Mayo Clinic between January 1, 1997, and
      December 31, 2015, were reviewed retrospectively. Descriptive statistics were
      used for data analysis. Fisher's exact test and the Wilcoxon rank sum test were
      used for analysis of categorical and continuous variables, respectively. All
      statistical tests were 2 sided, with the alpha level set at .05 for statistical
      significance. RESULTS: The time to diagnosis for 49% of patients was more than 1
      year. Three patients (3%) had vulval dysplasia, including invasive squamous cell
      carcinoma. Sixty-eight patients (68%) had multisite lichen planus disease. Eleven
      patients (11%) had disease remission. Dermatology was the lead specialty for 9 of
      these cases of remission. LIMITATIONS: This was a retrospective, small-cohort
      study. CONCLUSION: A low frequency of disease remission was seen in patients with
      VLP. Patients with lichen planus benefit considerably from dermatology
      consultation. Further research is warranted to establish high-quality, evidence
      based guidelines for multidisciplinary management of this challenging disease.

PMID- 29031661
TI  - Guidelines and algorithms for managing the difficult airway.
AB  - The difficult airway constitutes a continuous challenge for anesthesiologists.
      Guidelines and algorithms are key to preserving patient safety, by recommending
      specific plans and strategies that address predicted or unexpected difficult
      airway. However, there are currently no "gold standard" algorithms or universally
      accepted standards. The aim of this article is to present a synthesis of the
      recommendations of the main guidelines and difficult airway algorithms.

PMID- 29031662
TI  - Percutaneous treatment of hepatocellular carcinoma: State of the art and
      innovations.
AB  - Percutaneous treatment of hepatocellular carcinoma (HCC) encompasses a vast range
      of techniques, including monopolar radiofrequency ablation (RFA), multibipolar
      RFA, microwave ablation, cryoablation and irreversible electroporation. RFA is
      considered one of the main curative treatments for HCC of less than 5 cm
      developing on cirrhotic liver, together with surgical resection and liver
      transplantation. However, controversies exist concerning the respective roles of
      ablation and liver resection for HCC of less than 3 to 5 cm on cirrhotic liver.
      In line with the therapeutic algorithm of early HCC, percutaneous ablation could
      also be used as a bridge to liver transplantation or in a sequence of upfront
      percutaneous treatment, followed by transplantation if the patient relapses.
      Moreover, several innovations in ablation methods may help to efficiently treat
      early HCC, initially considered as "non-ablatable", and might, in some cases,
      extend ablation criteria beyond early HCC, enabling treatment of more patients
      with a curative approach.

PMID- 29031664
TI  - Nonlinearity-aware based dimensionality reduction and over-sampling for AD/MCI
      classification from MRI measures.
AB  - Alzheimer's disease (AD) has been not only a substantial financial burden to the
      health care system but also an emotional burden to patients and their families.
      Making accurate diagnosis of AD based on brain magnetic resonance imaging (MRI)
      is becoming more and more critical and emphasized at the earliest stages.
      However, the high dimensionality and imbalanced data issues are two major
      challenges in the study of computer aided AD diagnosis. The greatest limitations
      of existing dimensionality reduction and over-sampling methods are that they
      assume a linear relationship between the MRI features (predictor) and the disease
      status (response). To better capture the complicated but more flexible
      relationship, we propose a multi-kernel based dimensionality reduction and over
      sampling approaches. We combined Marginal Fisher Analysis with l2,1-norm based
      multi-kernel learning (MKMFA) to achieve the sparsity of region-of-interest
      (ROI), which leads to simultaneously selecting a subset of the relevant brain
      regions and learning a dimensionality transformation. Meanwhile, a multi-kernel
      over-sampling (MKOS) was developed to generate synthetic instances in the optimal
      kernel space induced by MKMFA, so as to compensate for the class imbalanced
      distribution. We comprehensively evaluate the proposed models for the diagnostic
      classification (binary class and multi-class classification) including all
      subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. The
      experimental results not only demonstrate the proposed method has superior
      performance over multiple comparable methods, but also identifies relevant
      imaging biomarkers that are consistent with prior medical knowledge.

PMID- 29031663
TI  - Advances in fMRI Real-Time Neurofeedback.
AB  - Functional magnetic resonance imaging (fMRI) neurofeedback is a type of
      biofeedback in which real-time online fMRI signals are used to self-regulate
      brain function. Since its advent in 2003 significant progress has been made in
      fMRI neurofeedback techniques. Specifically, the use of implicit protocols,
      external rewards, multivariate analysis, and connectivity analysis has allowed
      neuroscientists to explore a possible causal involvement of modified brain
      activity in modified behavior. These techniques have also been integrated into
      groundbreaking new neurofeedback technologies, specifically decoded neurofeedback
      (DecNef) and functional connectivity-based neurofeedback (FCNef). By modulating
      neural activity and behavior, DecNef and FCNef have substantially advanced both
      basic and clinical research.

PMID- 29031666
TI  - Reply by Authors.

PMID- 29031665
TI  - Stress distribution of metatarsals during forefoot strike versus rearfoot strike:
      A finite element study.
AB  - Due to the limitations of experimental approaches, comparison of the internal
      deformation and stresses of the human man foot between forefoot and rearfoot
      landing is not fully established. The objective of this work is to develop an
      effective FE modelling approach to comparatively study the stresses and energy in
      the foot during forefoot strike (FS) and rearfoot strike (RS). The stress level
      and rate of stress increase in the Metatarsals are established and the injury
      risk between these two landing styles is evaluated and discussed. A detailed
      subject specific FE foot model is developed and validated. A hexahedral dominated
      meshing scheme was applied on the surface of the foot bones and skin. An explicit
      solver (Abaqus/Explicit) was used to stimulate the transient landing process. The
      deformation and internal energy of the foot and stresses in the metatarsals are
      comparatively investigated. The results for forefoot strike tests showed an
      overall higher average stress level in the metatarsals during the entire landing
      cycle than that for rearfoot strike. The increase rate of the metatarsal stress
      from the 0.5 body weight (BW) to 2 BW load point is 30.76% for forefoot strike
      and 21.39% for rearfoot strike. The maximum rate of stress increase among the
      five metatarsals is observed on the 1st metatarsal in both landing modes. The
      results indicate that high stress level during forefoot landing phase may
      increase potential of metatarsal injuries.

PMID- 29031667
TI  - Editorial Comment.

PMID- 29031668
TI  - Editorial Comment.

PMID- 29031669
TI  - Reply by Authors.

PMID- 29031670
TI  - Editorial Comment.

PMID- 29031671
TI  - Editorial Comment.

PMID- 29031672
TI  - Editorial Comment.

PMID- 29031673
TI  - Editorial Comment.

PMID- 29031674
TI  - Editorial Comment.

PMID- 29031676
TI  - Persistent hyperplastic primary vitreous (PHPV).

PMID- 29031677
TI  - Spheno-orbital meningioma during pregnancy: Case report of a 37-year-old woman.

PMID- 29031678
TI  - Ileum Endometriosis: A Cause of Bowel Obstruction.

PMID- 29031679
TI  - "We Can Work It Out:" The Hundred Years' War between Experts of Surgical and
      Medical Treatment for Symptomatic Deep Endometriosis.

PMID- 29031680
TI  - Soluble expression and purification of a full-length asparaginyl tRNA synthetase
      from Fasciola gigantica.
AB  - We report the molecular cloning, expression, and single-step homogeneous
      purification of a full-length asparaginyl tRNA synthetase (NRS) from Fasciola
      gigantica (FgNRS). Fasciola gigantica is a parasitic liver fluke of the class
      Trematoda. It causes fascioliasis that infects the liver of various mammals,
      including humans. Aminoacyl tRNA synthetases (AARS) catalyze the first step of
      protein synthesis. They attach an amino acid to its cognate tRNA, forming an
      amino acid-tRNA complex. The gene that codes for FgNRS was generated by
      amplification by polymerase chain reaction. It was then inserted in the
      expression vector pQE30 under the transcriptional control of the bacteriophage T5
      promoter and lac operator. M15 Escherichia coli strain transformed with the FgNRS
      expression vector pQE30-NRS accumulates large amounts of a soluble protein of
      about 61 kDa. The protein was purified to homogeneity using immobilized metal
      affinity chromatography. The recombinant protein was further confirmed by
      immunoblotting with anti-His antibody. Following size exclusion chromatography,
      the FgNRS was stable and observed to be a dimeric protein. In this study, the
      expression and purification procedures have provided a simple and efficient
      method to obtain full-length FgNRS in large quantities. This will provide an
      opportunity to study the structure, dynamics and function of NRS.

PMID- 29031681
TI  - Altered rPrP substrate structures and their influence on real-time quaking
      induced conversion reactions.
AB  - BACKGROUND: Bacterially-produced recombinant prion protein (rPrP) has
      traditionally been used for in vitro fibrillation assays and reagent development
      for prion disease research. In recent years, it has also been used as a substrate
      for real-time quaking-induced conversion (RT-QuIC), a very sensitive method of
      detecting the presence of the misfolded, disease-associated isoform of the prion
      protein (PrPd). Multi-centre trials have demonstrated that RT-QuIC is a suitably
      reliable and robust technique for clinical practice; however, in the absence of a
      commercial supplier of rPrP as a substrate for RT-QuIC, laboratories have been
      required to independently generate this key component of the assay. No harmonized
      method for producing the protein has been agreed upon, in part due to the variety
      of substrates that have been applied in RT-QuIC. METHODS: This study examines the
      effects of two different rPrP refolding protocols on the production, QuIC
      performance, and structure characteristics of two constructs of rPrP commonly
      used in QuIC: full length hamster and a sheep-hamster chimeric rPrP. RESULTS:
      Under the described conditions, the best performing substrate was the chimeric
      sheep-hamster rPrP produced by shorter guanidine-HCl exposure and faster gradient
      elution. CONCLUSIONS: The observation that different rPrP production protocols
      influence QuIC performance indicates that caution should be exercised when
      comparing inter-laboratory QuIC results.

PMID- 29031682
TI  - [Rates of total and free PSA prescriptions in France (2012-2014)].
AB  - BACKGROUND: In 2010, the French Haute Autorite de sante (National Health
      Authority) confirmed the limited value of prostate cancer (PCa) screening by
      total prostate-specific antigen (PSA) assay. OBJECTIVE: This study was designed
      to determine the modalities of ordering total PSA or free PSA assays (in the
      absence of PCa) according to various parameters and the corresponding sums
      reimbursed. METHODS: Men aged 40 years and older covered by the national health
      insurance general scheme (73% of the French population) between 2012 and 2014
      were selected. Data were derived from the Systeme national d'information inter
      regimes de l'assurance maladie (Sniiram) (National health insurance information
      system) database. RESULTS: In 2014, 27% of the 11.6 million men 40 years and
      older underwent at least one total PSA assay and 5.6% underwent at least one free
      PSA assay, with marked variations according to the presence or absence of treated
      lower urinary tract symptoms (LUTS) (53% and 15% vs 24% and 5%) and from one
      administrative department to another. The peak total PSA assay rate was observed
      between the ages of 65 and 74 years: 64% of men with LUTS, 46% without LUTS.
      Between 2012 and 2014, men in whom at least one PSA assay had been performed
      underwent a mean of 1.8 total PSA assays and 1.7 free PSA assays, with means of
      2.3 and 2, respectively, in the presence of LUTS. General practice specialists
      ordered 91% of the PSA tests reimbursed in 2014 (92% for total PSA and 87% for
      free PSA) and urologists ordered 4% of reimbursed tests. The total sum reimbursed
      was ?28.5 million, comprising ?8.7 million for free PSA. An average of 10
      laboratory tests was performed at the same time as the PSA assay in the absence
      of treated LUTS. CONCLUSION: Total PSA and free PSA assays are performed in a
      large number of men, although the value of these tests as first-line test before
      biopsy remains controversial. These PSA assays are associated with many other
      laboratory tests looking for possible abnormalities, especially in younger men,
      and their relevance may therefore not be specifically discussed with the patient.

PMID- 29031683
TI  - [Focal therapies: An alternative option for low-risk prostate cancer management?]
AB  - Recommended options for low-risk prostate cancer treatment are active
      surveillance, radical treatments or watchful waiting. Focal therapies are
      currently assessed for low risk prostate cancer treatment. Focal therapies can be
      performed in research protocols. Oncologic results of these focal treatments are
      encouraging and show excellent tolerance with few complications. Radical
      treatments are still possible after focal therapies failure. Focal therapies are
      a possible solution to over-treatment issue of low risk prostate cancers.

PMID- 29031684
TI  - [Management of prostate cancer: The new challenges].

PMID- 29031685
TI  - Comparison of the composition of bile acids in bile of patients with
      adenocarcinoma of the pancreas and benign disease.
AB  - Bile acids have been implicated in the development of gastrointestinal
      malignancies. Both the specific nature of individual bile acids and their
      concentration appear key factors in the carcinogenic potency of bile. Using
      liquid chromatography mass spectrometry (LC-MS) we performed quantitative
      profiling of bile extracted directly from the common bile duct in 30 patients (15
      patients with pancreatic cancer and 15 patients with benign disease). Separation
      and detection of bile acids was performed using a 1.7MUm particle size reversed
      phase C18 LC column at a flow rate of 200MUL/min with negative electrospray
      ionization MS. A significant difference (p=0.018) was seen in the concentration
      of unconjugated cholic acid in the malignant group (0.643mmol/L) compared to the
      benign group (0.022mmol/L), with an overall significant difference (p=0.04) seen
      in the level of total unconjugated bile acids in the malignant group
      (1.816mmol/L) compared to the benign group (0.069mmol/L). This finding may offer
      the possibility of both understanding the biology of cancer development in the
      pancreas, as well as offering a potential diagnostic avenue to explore. However,
      a larger study is necessary to confirm the alterations in bile acid profiles
      reported here and explore factors such as diet and microbial populations on the
      bile acid profiles of these patient groups.

PMID- 29031686
TI  - Oestrogen receptor beta (ERbeta) regulates osteogenic differentiation of human
      dental pulp cells.
AB  - Estradiol (E2) has many important actions in the tissues of the oral cavity.
      Disruption of E2 metabolism or alterations in systemic E2 concentrations have
      been associated with compromised periodontal health. In many instances such
      changes occur secondarily to the well characterised effects of E2 on bone
      physiology -especially maintenance of bone mineral density (BMD). Despite these
      important epidemiological findings, little is known about the mechanism of action
      of E2 in oral tissues or the expression and function of oestrogen receptor (ER)
      isoforms in these tissues. We have isolated human dental pulp cells (hDPCs),
      which are able to differentiate towards an osteogenic lineage under appropriate
      culture conditions. We show that hDPCs express ERalpha, ERbeta1, ERbeta2 and the
      cell membrane associated G protein-coupled ER (GPR30). Following osteogenic
      differentiation of hDPCs, ERbeta1 and ERbeta2 were up regulated approximately 50
      fold while ERalpha and GPR30 were down regulated, but to a much lesser degree
      (approximately 2-fold). ERbeta was characterised as a 59kDa protein following
      Western blot analysis with validated antibodies and ERbeta was detected in both
      nuclear and cytoplasmic cell compartments following immunofluorescence (IF) and
      immunohistochemical (IHC) analysis of cultured cells. Furthermore isoform
      specific antibodies detected both ERbeta1 and ERbeta2 in DPC cultures and in situ
      analysis of ERbeta expression in decalcified tooth/pulp sections identified the
      odontoblast layer of pulp cells juxtaposed to the tooth enamel as strongly
      reactive for both ERbeta isoforms. Finally the use of isoform specific agonists
      identified ERbeta as the main receptor responsible for the pro-osteogenic effect
      of oestrogenic hormones in this tissue. Our data suggest that oestrogens
      stimulated osteogenic differentiation in hDPCs and that this action is mediated
      principally through the ERbeta isoform. These findings may have important
      consequences for the investigation and treatment of oral and periodontal
      pathologies which are associated with imbalances in oestrogen concentrations and
      action.

PMID- 29031687
TI  - Structure-function relationships for the selective inhibition of human 3beta
      hydroxysteroid dehydrogenase type 1 by a novel androgen analog.
AB  - 3beta-Hydroxysteroid dehydrogenase type 1 (3beta-HSD1) is selectively expressed
      in human placenta, mammary glands and breast tumors in women. Human 3beta-HSD2 is
      selectively expressed in adrenal glands and ovaries. Based on AutoDock 3 and 4
      results, we have exploited key differences in the amino acid sequences of 3beta
      HSD1 (Ser194, Arg195) and 3beta-HSD2 (Gly194, Pro195) by designing a selective
      inhibitor of 3beta-HSD1. 2,16-Dicyano-4,5-epoxy-androstane-3,17-dione (16-cyano
      17-keto-trilostane or DiCN-AND) was synthesized in a 4-step procedure from
      androstenedione. In purified 3beta-HSD inhibition studies, DiCN-AND competitively
      inhibited 3beta- HSD1 with Ki=4.7MUM and noncompetitively inhibited 3beta-HSD2
      with a 6.5-fold higher Ki=30.7MUM. We previously reported similar isoenzyme
      specific inhibition profiles for trilostane. Based on our docking results, we
      created, expressed and purified the chimeric S194G-1 mutant of 3beta-HSD1.
      Trilostane inhibited S194G-1 (Ki=0.67MUM) with a noncompetitive mode compared to
      its 6.7-fold higher affinity, competitive inhibition of 3beta-HSD1 (Ki=0.10MUM).
      DiCN-AND inhibited S194G-1 with a 6.3-fold higher Ki (29.5MUM) than measured for
      3beta-HSD1 (Ki=4.7MUM) but with the same competitive mode for both enzyme
      species. Since DiCN-AND noncompetitively inhibits 3beta-HSD2, which has the
      Gly194 and Pro195 of 3beta-HSD2 in place of the Ser194 and Arg195 in 3beta-HSD1,
      this suggests that Arg195 alone in 3beta-HSD1 or S194G-1 is required to bind DiCN
      AND in the substrate binding site (competitive inhibition). However, both Ser194
      and Arg195 are required to bind trilostane in the 3beta-HSD1 substrate site based
      on its noncompetitive inhibition of S194G-1 and 3beta-HSD2. In support of this
      hypothesis, DiCN-AND inhibited our chimeric R195P-1 mutant noncompetitively with
      a Ki=41.3MUM (similar to the 3beta-HSD2 inhibition profile). Since DiCN-AND
      competitively inhibited S194G-1 that still contains R195 but noncompetitively
      inhibited R195P-1 that still contains S194, our data provides strong evidence
      that the Arg195 being mutated to Pro195 (as present in 3beta-HSD2) shifts the
      inhibition mode from competitive to noncompetitive in 3beta-HSD1. This supports
      the key role of Arg195 in 3beta-HSD1 for the high affinity, competitive binding
      of the trilostane analogs. Our new structure/function information for the design
      of targeted 3beta-HSD1 inhibitors may lead to important new treatments for the
      prevention of spontaneous premature birth.

PMID- 29031690
TI  - Considerations for using ETEC and Shigella disease burden estimates to guide
      vaccine development strategy.
AB  - Enterotoxigenic E. coli (ETEC) and Shigella are enteropathogens causing
      significant global morbidity and mortality, particularly in low-income countries.
      No licensed vaccine exists for either pathogen, but candidates are in
      development, with the most advanced candidates potentially approaching pivotal
      efficacy testing within the next few years. A positive policy recommendation for
      introduction of any vaccine, following licensure, depends on evidence of vaccine
      cost-effectiveness and impact on morbidity and mortality. The mortality estimates
      for these two pathogens have fluctuated over recent years, which has led to
      uncertainty in the assessment of their relative public health importance for use
      in low and middle-income countries. This paper summarizes the various ETEC and
      Shigella disease burden estimates, based on a review of current literature and
      informal consultations with leading stakeholders in enteric disease modelling. We
      discuss the factors that underpin the variability, including differences in the
      modelling methodology; diagnostic tools used to ascertain diarrheal etiology;
      epidemiological setting; the data that are available to incorporate; and absolute
      changes in the total number of diarrheal deaths over time. We consider the
      further work that will strengthen the evidence needed to support future decision
      making with respect to recommendations on the relative utility of these vaccines.

PMID- 29031689
TI  - Oral administration of kaempferol inhibits bone loss in rat model of ovariectomy
      induced osteopenia.
AB  - BACKGROUND: Postmenopausal osteoporosis and osteoporotic fractures constitute an
      increasing problem in developing countries. Kaempferol, isolated from seeds of
      Cuscuta chinensis, is an active flavonoid inhibiting in vitro osteoclast
      activity. The aim of the presented research was an assessment of kaempferol
      effect on estrogen-deficiency-induced bone structure disturbances in rats.
      METHODS: The study was performed on 24 Wistar female rats divided into 3 groups:
      SHAM - rats undergoing a "sham" surgery, OVX-C - control group of animals that
      underwent ovariectomy, OVX-K - rats undergoing ovariectomy and receiving
      kaempferol for 8 weeks (from day 56 to day 112). RESULTS: In the OVX-K group,
      contrary to the OVX-C one, there was no significant decrease in femoral bone
      mineral density (BMD). A significant increase in Young's modulus was observed in
      the OVX-K group compared to the OVX-C (15.33+/-2.51GPa vs. 11.14+/-1.93GPa,
      p<0.05). A decreased bone turnover was detected in the OVX-K group. Tissue volume
      ratio (BV/TV) and trabecular bone perimeter were increased in the OVX-K group
      compared to the OVX-C one (0.241+/-0.037 vs. 0.170+/-0.022, p<0.05 and 15.52+/
      2.78mm vs. 9.67+/-3.07mm, p<0.05, respectively). CONCLUSION: Kaempferol has a
      beneficial influence on estrogen-deficiency-induced disturbances of bone
      structure in rats.

PMID- 29031688
TI  - Vitamin D deficiency is associated with poor breast cancer prognostic features in
      postmenopausal women.
AB  - This study aimed to evaluate the association between pretreatment vitamin D (VD)
      deficiency with breast cancer prognostic features in Brazilian postmenopausal
      women. An analytical cross sectional study was conducted with 192 women, aged 45
      75 years, attended at University Hospital. Women with recent diagnosis of breast
      cancer, in amenorrhea >12months and age >=45 years, without medication use or
      clinical conditions that interfere with VD values were included. Clinical and
      anthropometric data were collected. Serum level of 25 hydroxyvitamin D [25(OH)D]
      was measured in all patients until 20days after breast cancer diagnosis, and was
      classified as normal (>=30ng/mL), insufficiency (20-29ng/mL) and deficiency
      (<20ng/mL). Data on breast cancer (histopathological type, grade, tumor stage,
      lymph node status), hormone status (estrogen receptor, ER, progesterone receptor,
      PR), human epidermal growth factor receptor type 2 (HER2) and epithelial
      proliferative activity (Ki-67) were collected. For statistical analysis, the t
      student test, the Gamma Distribution (asymmetric variables), the chi-square test
      and the logistic regression (OR-odds ratio) were used. The median 25(OH)D level
      was 25.8ng/mL (range 12.0-59.2ng/mL). Sufficient vitamin D levels were detected
      in 65 patients (33.9%), whereas insufficient levels in 92 patients (47.9%), and
      deficient levels in 35 patients (18.2%). Participants with insufficient and
      deficient 25(OH)D levels had a higher proportion of tumors with a high grade and
      locally advanced and metastatic disease, more positive lymph node, a lower
      proportion of ER, PR positives tumors and higher Ki-67(p<0.05). Patients with
      normal vitamin D had a higher frequency of luminal A (47.7%) and luminal B
      (32.2%) tumors when compared to patients with vitamin D insufficiency or
      deficiency. Furthermore, all cases of triple negative were detected in women with
      low VD levels. Multivariate analysis, after adjusting for age, time since
      menopause and BMI, showed that insufficient and deficient level of vitamin D were
      significantly associated with negative estrogen receptor (OR 3.77 CI 95% 1.76
      8.09 and OR 3.99 CI 95% 1.83-8.68), high Ki-67 (OR 2.50, CI 95% 1.35-4.63, and OR
      2.62, CI 95% 1.40-4.98), and positive axillary lymph node status (OR 1.59, CI 95%
      1.03-2.33, and OR 1.58, CI 95% 1.02-2.92) respectively. In Brazilian
      postmenopausal women with breast cancer, there was an association between vitamin
      D insufficiency or deficiency and tumors with worse prognostic features. Low
      vitamin D levels were shown to be a risk factor for ER negative tumors, with
      positive axilla and a higher rate of cell proliferation.

PMID- 29031691
TI  - Understanding vaccine hesitancy in polio eradication in northern Nigeria.
AB  - BACKGROUND: Vaccine hesitancy constitutes a major threat to the Global Polio
      Eradication Initiative (GPEI), and to further expansion of routine immunisation.
      Understanding hesitancy, leading in some cases to refusal, is vital to the
      success of GPEI. Re-emergence of circulating wild poliovirus in northern Nigeria
      in mid-2016, after 24months polio-free, gives urgency to this. But it is equally
      important to protect and sustain the global gains available through routine
      immunisation in a time of rising scepticism and potential rejection of specific
      vaccines or immunisation more generally. METHODS AND FINDINGS: This study is
      based on a purposive sampling survey of 1653 households in high- and low
      performing rural, semiurban and urban areas of three high-risk states of northern
      Nigeria in 2013-14 (Sokoto, Kano and Bauchi). The survey sought to understand
      factors at household and community level associated with propensity to refuse
      polio vaccine. Wealth, female education and knowledge of vaccines were associated
      with lower propensity to refuse oral polio vaccine (OPV) among rural households.
      But higher risk of refusal among wealthier, more literate urban household
      rendered these findings ambiguous. Ethnic and religious identity did not appear
      to be associated with risk of OPV refusal. Risk of vaccine refusal was highly
      clustered among households within a small sub-group of sampled settlements.
      Contrary to expectations, households in these settlements reported higher levels
      of expectation of government as service provider, but at the same time lesser
      confidence in the efficacy of their relations with government. CONCLUSIONS:
      Results suggest that strategies to address the micro-political dimension of
      vaccination - expanding community-level engagement, strengthening the role of
      local government in public health, and enhancing public participation of women -
      should be effective in reducing non-compliance, asan important set of strategies
      complementary to conventional didactic/educational approaches and working through
      religious and traditional 'influencers'.

PMID- 29031692
TI  - Development and application of a bioluminescent imaging mouse model for
      Chikungunya virus based on pseudovirus system.
AB  - Chikungunya virus (CHIKV) is an arthropod-borne virus that is transmitted to
      humans primarily via the bite of an infected mosquito. Infection of humans by
      CHIKV can cause chikungunya fever which is an acute febrile illness associated
      with severe, often debilitating polyarthralgias. Since a re-emergence of CHIKV in
      2004, the virus has spread into novel locations in nearly 40 countries including
      non-endemic regions and has led to millions of cases of disease throughout
      countries. Handling of CHIKV is restricted to the high-containment Biosafety
      Level 3 (BSL-3) facilities, which greatly impede the research progress of this
      virus. In this study, an envelope-pseudotyped virus expressing the firefly
      luciferase reporter protein (pHIV-CHIKV-Fluc) was generated. An in vitro
      sensitive neutralizing assay and an in vivo bioluminescent-imaging-based mouse
      infection model had been developed based on the CHIKV pseudovirus. Utilizing the
      platform, protection effect of DNA vaccine was evaluated. Therefore, this study
      provides a safe, sensitive and visualizing model for evaluating vaccines and
      antiviral therapies against CHIKV in low containment BSL-2 laboratories.

PMID- 29031693
TI  - A brief review on the immunological scenario and recent developmental status of
      vaccines against enteric fever.
AB  - Enteric fever has been one of the leading causes of severe illness and deaths
      worldwide. S. Typhi and S. Paratyphi A, B and C are important enteric fever
      causing organisms globally. This infection causes about 21 million cases among
      which 222,000 typhoid related deaths occurred in 2015. These estimates do not
      reflect the ultimate and real status of the disease due to the lack of unified
      diagnostic and proper reporting system from typhoid endemic and other regions.
      Current control strategies have become increasingly ineffective due to the
      emergence of multi-drug resistance among the strains. This situation worsens the
      disease-burden in developing as well as in developed countries. Moreover the
      emergence of S. Paratyphi A as a major enteric fever-causing organism in several
      Asian countries, demands a prophylactic measure at this hour. Other than two
      licensed vaccines of S. Typhi, there are no exsisting vaccines for S. Paratyphi
      A. Moreover, travelers returning from endemic regions are becoming more
      susceptible to have these infections. In this situation, a need for bivalent
      approach is required where a single immunogen (consisting from each organism)
      will be effective against the disease. In this review, we have focused on the
      general information about typhoidal fever, its spread and epidemiology in brief
      and the present status of typhoidal vaccines and its future. This review
      highlights existing gaps in the typhoidal salmonellae research with a special
      emphasis on the status of present typhoidal salmonellae vaccine research.

PMID- 29031694
TI  - A formative research-guided educational intervention to improve the knowledge and
      attitudes of seniors towards influenza and pneumococcal vaccinations.
AB  - BACKGROUND: Adult influenza and pneumococcal vaccination rates in Singapore are
      low, and factors influencing knowledge and attitudes of seniors towards
      influenza, pneumonia and their respective vaccines are not well-known. Our study
      aims to understand the barriers and facilitators towards getting influenza and
      pneumococcal vaccinations among seniors in Singapore, and subsequently inform the
      conduct of a relevant community-based educational intervention, as well as
      evaluate the intervention outcomes. METHODS: We performed a mixed methods study
      with two components: Firstly, formative research was conducted among community
      dwelling seniors, using focus group discussions (FGDs), to understand their
      knowledge and attitudes towards influenza, pneumonia and their respective
      vaccines. Next, a quantitative study was conducted to evaluate knowledge of
      seniors and the effectiveness of an educational intervention. RESULTS: Four FGDs
      were organised with 32 participants, who were predominantly female, of lower
      educational background, and residing in government rental flats. Participants had
      varying levels of knowledge and many misconceptions about influenza, pneumonia
      and their respective vaccinations, with concerns about side effects and vaccine
      effectiveness. The formative research results were used to inform a community
      based educational intervention for seniors. Our subsequent evaluation included
      604 elderly participants, mainly from lower educational and socio-economic
      strata, who initially demonstrated poor knowledge scores (median score 5 out of
      9, IQR 4-5). Following our intervention, median knowledge score improved to 7
      (IQR 6-8) (p < .0001). Significant improvements in knowledge scores were observed
      across genders, age strata, education levels, and housing types. DISCUSSION: Our
      formative research identified knowledge gaps among community-dwelling seniors
      which affected their attitudes towards vaccination uptake. Key findings were
      taken into consideration when implementing the educational intervention. Our
      community-based intervention was effective in improving knowledge and attitudes,
      and could be used as a cue to action for short-term behaviour changes.

PMID- 29031695
TI  - 'Hesitant compliers': Qualitative analysis of concerned fully-vaccinating
      parents.
AB  - OBJECTIVE: Some parents are hesitant about vaccines and yet still vaccinate their
      children. Vaccine behaviours are not fixed and parents who are concerned but
      nonetheless adherent to standard schedules could switch to an unconventional
      schedule, delaying or cherry-picking vaccines. There is a need to better
      understand vaccine hesitancy in specific contexts, acknowledging cultural and
      geographical variation, to ensure interventions targeting hesitancy are well
      directed and received. METHODS: To identify the behaviours, knowledge and
      attitudes of 'hesitant compliers' in Perth, Western Australia, nine one-on-one in
      depth interviews were conducted with vaccinating parents of children (<5 years)
      who were identified as being hesitant. Interview transcripts were analysed
      qualitatively and themes developed inductively, following a constructivist
      paradigm. RESULTS: Parents saw vaccination as important for themselves and their
      community, despite their limited knowledge of vaccine preventable diseases.
      Parents reported concerns about potential side effects, and worried about the
      safety of the measles-mumps-rubella (MMR) and seasonal influenza vaccines.
      Concerned about the role of anti-vaccination information in the community, some
      sought to isolate themselves from parents who did not vaccinate, although others
      were concerned that this could entrench non-vaccinators' behaviours. Parents'
      views were all underlaid by two pivotal 'vaccine-related events' that had
      occurred in the community: the severe injury of a baby from seasonal influenza
      vaccination in 2010, and the death of a baby from whooping cough in 2015.
      CONCLUSIONS: Parents interpreted pivotal vaccine-related events in the community
      as requiring them to take personal responsibility for vaccine decisions. Their
      reports of continued vaccine fears (evident in international studies in recent
      decades) demonstrate that vaccine scares have long lasting effects. With vaccine
      rates high and stable, current strategies appear to be have little impact on
      addressing parental vaccine concerns. Further research is required to determine
      the prevalence of hesitancy amongst vaccinating parents and identify critical
      points for intervention.

PMID- 29031696
TI  - Safety assessment of immunization in pregnancy.

PMID- 29031698
TI  - Aggregation of Abeta(17-36) in the Presence of Naturally Occurring Phenolic
      Inhibitors Using Coarse-Grained Simulations.
AB  - Although some naturally occurring polyphenols have been found to inhibit amyloid
      beta (Abeta) fibril formation and reduce neuron cell toxicity in vitro, their
      exact inhibitory mechanism is unknown. In this work, discontinuous molecular
      dynamics combined with the PRIME20 force field and a newly built inhibitor model
      are performed to examine the effect of vanillin, resveratrol, curcumin, and
      epigallocatechin-3-gallate (EGCG) on the aggregation of Abeta(17-36) peptides.
      Four sets of peptide/inhibitor simulations are performed in which inhibitors (1)
      bind to Abeta(17-36) monomer (2) interfere with Abeta(17-36) oligomerization (3)
      disrupt a pre-formed Abeta(17-36) protofilament, and (4) prevent the growth of
      Abeta(17-36) protofilament. The single-ring compound, vanillin, slightly slows
      down but cannot inhibit the formation of a U-shaped Abeta(17-36) protofilament.
      The multiple-ring compounds, EGCG, resveratrol, and curcumin, redirect Abeta(17
      36) from a fibrillar aggregate to an unstructured oligomer. The three aromatic
      groups of the EGCG molecule are in a stereo (nonplanar) configuration, helping it
      contact the N-terminal, middle, and C-terminal regions of the peptide.
      Resveratrol and curcumin bind only to the hydrophobic residues near peptide
      termini. The rank order of inhibitory effectiveness of Abeta(17-36) aggregation
      is as follows: EGCG > resveratrol > curcumin > vanillin, consistent with
      experimental findings on inhibiting full-length Abeta fibrillation. Furthermore,
      we learn that the inhibition effect of EGCG is specific to the peptide sequence,
      while those of resveratrol and curcumin are non-specific in that they stem from
      strong interference with hydrophobic side-chain association, regardless of the
      residues' location and peptide sequence. Our studies provide molecular-level
      insights into how polyphenols inhibit Abeta fibril formation, knowledge that
      could be useful for designing amyloid inhibitors.

PMID- 29031697
TI  - Ubiquitin-Modifying Enzymes and Regulation of the Inflammasome.
AB  - Ubiquitin and ubiquitin-modifying enzymes play critical roles in a wide variety
      of intracellular signaling pathways. Inflammatory signaling cascades downstream
      of TNF, TLR agonists, antigen receptor cross-linking, and cytokine receptors, all
      rely on ubiquitination events to direct subsequent immune responses. In the past
      several years, inflammasome activation and subsequent signal transduction have
      emerged as an excellent example of how ubiquitin signals control inflammatory
      responses. Inflammasomes are multiprotein signaling complexes that ultimately
      lead to caspase activation and release of the interleukin-1 (IL-1) family
      members, IL-1beta and IL-18. Inflammasome activation is critical for the host's
      defense against pathogens, but dysregulation of inflammasomes may contribute to
      the pathogenesis of multiple diseases. Ultimately, understanding how various
      ubiquitin interacting proteins control inflammatory signaling cascades could
      provide new pathways for therapeutic intervention. Here we review specific
      ubiquitin-modifying enzymes and ubiquitination events that orchestrate
      inflammatory responses, with an emphasis on the NLRP3 inflammasome.

PMID- 29031699
TI  - A Genetic Tool to Quantify trans-Translation Activity in Vivo.
AB  - In bacteria, trans-translation is the main quality control mechanism for rescuing
      ribosomes arrested during translation. This key process is universally conserved
      and plays a critical role in the viability and virulence of many pathogens. We
      developed a reliable in vivo double-fluorescence reporter system for the
      simultaneous quantification of both trans-translation and the associated
      proteolysis activities in bacteria. The assay was validated using mutant bacteria
      lacking tmRNA, SmpB, and the ClpP protease. Both antisense tmRNA-binding RNA and
      a peptide mimicking the SmpB C-terminal tail proved to be potent inhibitors of
      trans-translation in vivo. The double-fluorescent reporter was also tested with
      KKL-35, an oxadiazole derivative that is supposed to be a promising trans
      translation inhibitor, and it surprisingly turns out that trans-translation is
      not the only target of KKL-35 in vivo.

PMID- 29031700
TI  - Cost Benefit of Comprehensive Primary and Preventive School-Based Health Care.
AB  - INTRODUCTION: The Rales Health Center is a comprehensive school-based health
      center at an urban elementary/middle school. Rales Health Center provides a full
      range of pediatric services using an enriched staffing model consisting of
      pediatrician, nurse practitioner, registered nurses, and medical office
      assistant. This staffing model provides greater care but costs more than
      traditional school-based health centers staffed by part-time nurses. The
      objective was to analyze the cost benefit of Rales Health Center enhanced
      staffing model compared with a traditional school-based health center (standard
      care), focusing on asthma care, which is among the most prevalent chronic
      conditions of childhood. METHODS: In 2016, cost-benefit analysis using a decision
      tree determined the net social benefit of Rales Health Center compared with
      standard care from the U.S. societal perspective based on the 2015-2016 academic
      year. It was assumed that Rales Health Center could handle greater patient
      throughput related to asthma, decreased prescription costs, reduced parental
      resources in terms of missed work time, and improved student attendance.
      Univariate and multivariate probabilistic sensitivity analyses were conducted.
      RESULTS: The expected cost to operate Rales Health Center was $409,120, compared
      with standard care cost of $172,643. Total monetized incremental benefits of
      Rales Health Center were estimated to be $993,414. The expected net social
      benefit for Rales Health Center was $756,937, which demonstrated substantial
      societal benefit at a return of $4.20 for every dollar invested. This net social
      benefit estimate was robust to sensitivity analyses. CONCLUSIONS: Despite the
      greater cost associated with the Rales Health Center's enhanced staffing model,
      the results of this analysis highlight the cost benefit of providing
      comprehensive, high-quality pediatric care in schools, particularly schools with
      a large proportion of underserved students.

PMID- 29031701
TI  - [Old privilege and enthusiast progress].

PMID- 29031702
TI  - Complications following open reduction and internal fixation versus external
      fixation in treating unstable distal radius fractures: Grading the evidence
      through a meta-analysis.
AB  - BACKGROUND: The common fixation techniques for unstable distal radius fractures
      include open reduction and internal fixation (ORIF) with plates and closed
      reduction and external fixation (EF). There is controversy over the choice of
      surgical approach in treating unstable distal radius fractures. HYPOTHESIS: This
      meta-analysis was performed to compare complication rates in patients treated
      with ORIF or EF for unstable distal radius fractures and to develop GRADE
      (grading of recommendations, assessment, development, and evaluation)-based
      recommendations for using the procedures to treat unstable distal radius
      fractures. MATERIALS AND METHODS: A systematic search of all the studies
      published was conducted using the Pubmed, ScienceDirect, Embase, BIOSIS,
      Springer, Cochrane Library databases. The randomized controlled trials (RCTs)
      that compared ORIF with EF in treating adult patients with unstable distal radius
      fractures and provided data regarding the complication were identified. The
      demographic characteristics and adverse events were manually extracted from all
      of the included studies. RevMan 5.1 was used for data analysis. PRISMA guidelines
      were followed. RESULTS: Sixteen studies that included a total of 1280 patients
      met the inclusion criteria. Compared with ORIF, EF results in higher incidence of
      total complications, infection and malunion. The overall GRADE system evidence
      quality was very low, which reduces our confidence in the recommendations of this
      system. DISCUSSION: This meta-analysis indicates that ORIF and EF are both
      effective procedures for treating unstable distal radius fractures. ORIF may be
      superior to EF in the treatment of unstable distal radius fractures. Because of
      the low quality evidence currently available, high-quality RCTs are required.
      LEVEL OF EVIDENCE: Level II: low-powered prospective randomized trial meta
      analysis.

PMID- 29031703
TI  - Comparative approximations of criticality in a neural and quantum regime.
AB  - Under a variety of conditions, stochastic and non-linear systems with many
      degrees of freedom tend to evolve towards complexity and criticality. Over the
      last decades, a steady proliferation of models re: far-from-equilibrium
      thermodynamics of metastable, many-valued systems arose, serving as attributes of
      a 'critical' attractor landscape. Building off recent data citing trademark
      aspects of criticality in the brain-including: power-laws, scale-free (1/f)
      behavior (scale invariance, or scale independence), critical slowing, and
      avalanches-it has been conjectured that operating at criticality entails
      functional advantages such as: optimized neural computation and information
      processing; boosted memory; large dynamical ranges; long-range communication; and
      an increased ability to react to highly diverse stimuli. In short, critical
      dynamics provide a necessary condition for neurobiologically significant elements
      of brain dynamics. Theoretical predictions have been verified in specific models
      such as Boolean networks, liquid state machines, and neural networks. These
      findings inspired the neural criticality hypothesis, proposing that the brain
      operates in a critical state because the associated optimal computational
      capabilities provide an evolutionarily advantage. This paper develops in three
      parts: after developing the critical landscape, we will then shift gears to
      rediscover another inroad to criticality via stochastic quantum field theory and
      dissipative dynamics. The existence of these two approaches deserves some
      consideration, given both neural and quantum criticality hypotheses propose
      specific mechanisms that leverage the same phenomena. This suggests that
      understanding the quantum approach could help to shed light on brain-based
      modeling. In the third part, we will turn to Whitehead's actual entities and
      modes of perception in order to demonstrate a concomitant logic underwriting both
      models. In the discussion, I briefly motivate a reading of criticality and its
      properties as responsive to the characterization of tenets from Eastern wisdom
      traditions.

PMID- 29031704
TI  - Evaluation of cooperative antileukemic effects of nilotinib and vildagliptin in
      Ph+ chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) is a stem cell (SC) neoplasm characterized by the
      BCR/ABL1 oncogene. Although the disease can be kept under control using BCR/ABL1
      tyrosine kinase inhibitors (TKIs) in most cases, some patients relapse or have
      resistant disease, so there is a need to identify new therapeutic targets in this
      malignancy. Recent data suggest that leukemic SCs (LSCs) in CML display the stem
      cell (SC)-mobilizing cell surface enzyme dipeptidyl-peptidase IV (DPPIV = CD26)
      in an aberrant manner. In the present study, we analyzed the effects of the DPPIV
      blocker vildagliptin as single agent or in combination with the BCR/ABL1 TKI
      imatinib or nilotinib on growth and survival of CML LSCs in vitro and on LSC
      engraftment in an in vivo xenotransplantation nonobese diabetic SCID-IL-2Rgamma-/
      (NSG) mouse model. We found that nilotinib induces apoptosis in CML LSCs and
      inhibits their engraftment in NSG mice. In contrast, no substantial effects were
      seen with imatinib or vildagliptin. Nevertheless, vildagliptin was found to
      reduce the "mobilization" of CML LSCs from a stroma cell layer consisting of
      mouse fibroblasts in an in vitro co-culture model, suggesting reduced disease
      expansion. However, although vildagliptin and nilotinib produced cooperative
      effects in individual experiments, overall, no significant effects of
      coadministered vildagliptin over nilotinib or imatinib treatment alone were seen
      on the engraftment of CML cells in NSG mice. Gliptins may be interesting drugs in
      the context of CML and nilotinib therapy, but our preclinical studies did not
      reveal a major cooperative effect of the drug-combination vildagliptin +
      nilotinib on engraftment of CML cells in NSG mice.

PMID- 29031705
TI  - Laparoscopic Repair of Large Hiatal Hernia Without the Need for Esophageal
      Lengthening With Low Morbidity and Rare Symptomatic Recurrence.
AB  - The aim of this study was to assess symptomatic recurrence in patients who
      underwent a laparoscopic repair of large hiatal hernia without an esophageal
      lengthening procedure. Patients who underwent a laparoscopic repair of a large
      hiatal hernia from September 2009 to September 2015 by a single surgeon were
      identified in the retrospective review. The patients were followed up
      prospectively by the operating surgeon using a structured questionnaire,
      administered by telephone, to assess the symptoms. Symptomatic recurrence was
      defined as the requirement for a reoperative procedure for symptomatic recurrent
      hiatal hernia. There were 215 laparoscopic repairs. Reoperations (n = 35) and
      type I hernias of <4 cm (n = 49) were excluded. The study population included 131
      patients: 36 had type I hernia, 4 had type II hernia, 37 had type III hernia, and
      54 had type IV hernia. There were 102 women and 29 men, aged 63 (56-74) years.
      For repair, 102 Toupet, 28 Nissen, and 1 Dor fundoplications were performed. The
      duration of the operation was 138 (119-172) minutes. Adequate esophageal length
      was obtained by mediastinal esophageal mobilization in all patients, without
      Collis gastroplasty. A mesh was used in 106 patients. There was 1 conversion and
      2 delayed esophageal leaks. The length of stay was 2 (1-3) days. Perioperative
      complications included atrial fibrillation in 5 patients, gastric distension or
      ileus in 5 patients, reintubation in 3 patients, heparin-induced thrombocytopenia
      in 1 patient, and temporary dialysis in 1 patient. There was no 30-day or in
      hospital mortality. The questionnaire was completed by 99 out of 131 patients
      (76%) at 24 (9-38) months; of the 99 patients, 85 (86%) were free of preoperative
      symptoms; 91 (92%) were satisfied with the operation; and 73 (74%) were off
      proton pump inhibitors. Reoperation for symptomatic recurrent hiatal hernia
      occurred in 8 of the 99 patients (8%), 2 in the perioperative period and 6 at 25
      (8-31) months. Laparoscopic repair of large hiatal hernia can be performed with
      low morbidity and results in excellent patient satisfaction. Tension-free, intra
      abdominal esophageal length can be achieved laparoscopically without Collis
      gastroplasty. Reoperation for symptomatic recurrence is rare.

PMID- 29031706
TI  - Early Outcomes with Rapid-deployment vs Stented Biological Valves: A Propensity
      match Analysis.
AB  - Rapid-deployment valves could potentially reduce cross-clamping time and
      cardiopulmonary bypass time in complex combined procedures and facilitate
      minimally invasive surgery. This propensity-matched study compared clinical and
      echographic outcomes between patients undergoing rapid-deployment aortic valve
      replacement (RDAVR) compared with stented biological aortic valve replacement
      (SAVR), with or without concomitant procedures. Between 2012 and 2015, 61
      consecutive patients (age 70 +/- 7 years, European System for Cardiac Operative
      Risk Evaluation [EuroSCORE] II 2.1%) underwent aortic valve replacement with
      Intuity prosthesis (Edwards, Irvine, CA) at the Montreal Heart Institute. This
      group was compared to 1496 consecutive patients (age 74 +/- 8 years, logistic
      EuroSCORE II 2.8%) who underwent SAVR in the same period. After propensity score
      matching (1:3), 59 patients in the RDAVR group were matched to 177 patients in
      the SAVR group. Preoperative characteristics and risk scores were similar in
      matched groups. Cardiopulmonary bypass, cross-clamp, and total surgical times
      were lower in the RDAVR group compared with the SAVR group (P < 0.001). Within 30
      days, 1 patient died in the SAVR group and none died in the RDAVR group (P =
      0.31). The need for pacemaker implantation was higher in the RDAVR group,
      although the difference was not significant (12% vs 5%, P = 0.13). RDAVR patients
      less frequently required transfusions (P = 0.025) and had a shorter intubation
      time (P = 0.002). RDAVR facilitates minimally invasive aortic valve replacement
      and is associated with shorter bypass and cross-clamp times. Moreover, RDAVR
      compares favorably with SAVR in terms of mortality and outcome variables.

PMID- 29031707
TI  - Modeling host-seeking behavior of African malaria vector mosquitoes in the
      presence of long-lasting insecticidal nets.
AB  - The efficiency of spatial repellents and long-lasting insecticide-treated nets
      (LLINs) is a key research topic in malaria control. Insecticidal nets reduce the
      mosquito-human contact rate and simultaneously decrease mosquito populations.
      However, LLINs demonstrate dissimilar efficiency against different species of
      malaria mosquitoes. Various factors have been proposed as an explanation,
      including differences in insecticide-induced mortality, flight characteristics,
      or persistence of attack. Here we present a discrete agent-based approach that
      enables the efficiency of LLINs, baited traps and Insecticide Residual Sprays
      (IRS) to be examined. The model is calibrated with hut-level experimental data to
      compare the efficiency of protection against two mosquito species: Anopheles
      gambiae and Anopheles arabiensis. We show that while such data does not allow an
      unambiguous identification of the details of how LLINs alter the vector behavior,
      the model calibrations quantify the overall impact of LLINs for the two different
      mosquito species. The simulations are generalized to community-scale scenarios
      that systematically demonstrate the lower efficiency of the LLINs in control of
      An. arabiensis compared to An. gambiae.

PMID- 29031708
TI  - The brain strikes back: Hypothalamic targets for peripheral CB1 receptor inverse
      agonism.

PMID- 29031709
TI  - Anti-hypertensive treatment in pregnancy impacts offspring growth and metabolism:
      Q&A.

PMID- 29031710
TI  - Nav1.8 neurons are involved in limiting acute phase responses to dietary fat.
AB  - OBJECTIVE AND METHODS: Metabolic viscera and their vasculature are richly
      innervated by peripheral sensory neurons. Here, we examined the metabolic and
      inflammatory profiles of mice with selective ablation of all Nav1.8-expressing
      primary afferent neurons. RESULTS: While mice lacking sensory neurons displayed
      no differences in body weight, food intake, energy expenditure, or body
      composition compared to controls on chow diet, ablated mice developed an
      exaggerated inflammatory response to high-fat feeding characterized by bouts of
      weight loss, splenomegaly, elevated circulating interleukin-6 and hepatic serum
      amyloid A expression. This phenotype appeared to be directly mediated by the
      ingestion of saturated lipids. CONCLUSIONS: These data demonstrate that the
      Nav1.8-expressing afferent neurons are not essential for energy balance but are
      required for limiting the acute phase response caused by an obesogenic diet.

PMID- 29031711
TI  - Lorcaserin improves glycemic control via a melanocortin neurocircuit.
AB  - OBJECTIVE: The increasing prevalence of type 2 diabetes (T2D) and associated
      morbidity and mortality emphasizes the need for a more complete understanding of
      the mechanisms mediating glucose homeostasis to accelerate the identification of
      new medications. Recent reports indicate that the obesity medication lorcaserin,
      a 5-hydroxytryptamine (5-HT, serotonin) 2C receptor (5-HT2CR) agonist, improves
      glycemic control in association with weight loss in obese patients with T2D. Here
      we evaluate whether lorcaserin has an effect on glycemia without body weight loss
      and how this effect is achieved. METHODS: Murine models of common and genetic T2D
      were utilized to probe the direct effect of lorcaserin on glycemic control.
      RESULTS: Lorcaserin dose-dependently improves glycemic control in mouse models of
      T2D in the absence of reductions in food intake or body weight. Examining the
      mechanism of this effect, we reveal a necessary and sufficient neurochemical
      mediator of lorcaserin's glucoregulatory effects, brain pro-opiomelanocortin
      (POMC) peptides. To clarify further lorcaserin's therapeutic brain circuit, we
      examined the receptor target of POMC peptides. We demonstrate that lorcaserin
      requires functional melanocortin4 receptors on cholinergic preganglionic neurons
      (MC4RChAT) to exert its effects on glucose homeostasis. In contrast, MC4RChAT
      signaling did not impact lorcaserin's effects on feeding, indicating a divergence
      in the neurocircuitry underpinning lorcaserin's therapeutic glycemic and
      anorectic effects. Hyperinsulinemic-euglycemic clamp studies reveal that
      lorcaserin reduces hepatic glucose production, increases glucose disposal and
      improves insulin sensitivity. CONCLUSIONS: These data suggest that lorcaserin's
      action within the brain represents a mechanistically novel treatment for T2D:
      findings of significance to a prevalent global disease.

PMID- 29031712
TI  - Mitochondrial uncoupling in the melanocortin system differentially regulates NPY
      and POMC neurons to promote weight-loss.
AB  - OBJECTIVE: The mitochondrial uncoupling agent 2,4-dinitrophenol (DNP),
      historically used as a treatment for obesity, is known to cross the blood-brain
      barrier, but its effects on central neural circuits controlling body weight are
      largely unknown. As hypothalamic melanocortin neuropeptide Y/agouti-related
      protein (NPY/AgRP) and pro-opiomelanocortin (POMC) neurons represent key central
      regulators of food intake and energy expenditure we investigated the effects of
      DNP on these neurons, food intake and energy expenditure. METHOD: C57BL/6 and
      melanocortin-4 receptor (MC4R) knock-out mice were administered DNP
      intracerebroventricularly (ICV) and the metabolic changes were characterized. The
      specific role of NPY and POMC neurons and the ionic mechanisms mediating the
      effects of uncoupling were examined with in vitro electrophysiology performed on
      NPY hrGFP or POMC eGFP mice. RESULTS: Here we show DNP-induced differential
      effects on melanocortin neurons including inhibiting orexigenic NPY and
      activating anorexigenic POMC neurons through independent ionic mechanisms coupled
      to mitochondrial function, consistent with an anorexigenic central effect.
      Central administration of DNP induced weight-loss, increased BAT thermogenesis
      and browning of white adipose tissue, and decreased food intake, effects that
      were absent in MC4R knock-out mice and blocked by the MC4R antagonist, AgRP.
      CONCLUSION: These data show a novel central anti-obesity mechanism of action of
      DNP and highlight the potential for selective melanocortin mitochondrial
      uncoupling to target metabolic disorders.

PMID- 29031713
TI  - Peripheral cannabinoid-1 receptor blockade restores hypothalamic leptin
      signaling.
AB  - OBJECTIVE: In visceral obesity, an overactive endocannabinoid/CB1 receptor (CB1R)
      system promotes increased caloric intake and decreases energy expenditure, which
      are mitigated by global or peripheral CB1R blockade. In mice with diet-induced
      obesity (DIO), inhibition of food intake by the peripherally restricted CB1R
      antagonist JD5037 could be attributed to endogenous leptin due to the rapid
      reversal of hyperleptinemia that maintains leptin resistance, but the signaling
      pathway engaged by leptin has remained to be determined. METHODS: We analyzed the
      hypothalamic circuitry targeted by leptin following chronic treatment of DIO mice
      with JD5037. RESULTS: Leptin treatment or an increase in endogenous leptin
      following fasting/refeeding induced STAT3 phosphorylation in neurons in the
      arcuate nucleus (ARC) in lean and JD5037-treated DIO mice, but not in vehicle
      treated DIO animals. Co-localization of pSTAT3 in leptin-treated mice was
      significantly less common with NPY+ than with POMC+ ARC neurons. The hypophagic
      effect of JD5037 was absent in melanocortin-4 receptor (MC4R) deficient obese
      mice or DIO mice treated with a MC4R antagonist, but was maintained in NPY-/-
      mice kept on a high-fat diet. CONCLUSIONS: Peripheral CB1R blockade in DIO
      restores sensitivity to endogenous leptin, which elicits hypophagia via the re
      activation of melanocortin signaling in the ARC.

PMID- 29031714
TI  - Dwarfism and insulin resistance in male offspring caused by alpha1-adrenergic
      antagonism during pregnancy.
AB  - OBJECTIVE: Maternal and environmental factors control the epigenetic fetal
      programming of the embryo, thereby defining the susceptibility for metabolic or
      endocrine disorders in the offspring. Pharmacological interventions required as a
      consequence of gestational problems, e.g. hypertension, can potentially interfere
      with correct fetal programming. As epigenetic alterations are usually only
      revealed later in life and not detected in studies focusing on early perinatal
      outcomes, little is known about the long-term epigenetic effects of gestational
      drug treatments. We sought to test the consequences of maternal alpha1-adrenergic
      antagonism during pregnancy, which can occur e.g. during hypertension treatment,
      for the endocrine and metabolic phenotype of the offspring. METHODS: We treated
      C57BL/6NCrl female mice with the alpha1-adrenergic antagonist prazosin during
      pregnancy and analyzed the male and female offspring for endocrine and metabolic
      abnormalities. RESULTS: Our data revealed that maternal alpha1-adrenergic
      blockade caused dwarfism, elevated body temperature, and insulin resistance in
      male offspring, accompanied by reduced IGF-1 serum concentrations as the result
      of reduced hepatic growth hormone receptor (Ghr) expression. We subsequently
      identified increased CpG DNA methylation at the transcriptional start site of the
      alternative Ghr promotor caused by the maternal treatment, which showed a strong
      inverse correlation to hepatic Ghr expression. CONCLUSIONS: Our results
      demonstrate that maternal alpha1-adrenergic blockade can constitute an epigenetic
      cause for dwarfism and insulin resistance. The findings are of immediate clinical
      relevance as combined alpha/beta-adrenergic blockers are first-line treatment of
      maternal hypertension.

PMID- 29031715
TI  - ANGPTL8 promotes the ability of ANGPTL3 to bind and inhibit lipoprotein lipase.
AB  - OBJECTIVE: Several members of the angiopoietin-like (ANGPTL) family of proteins,
      including ANGPTL3 and ANGPTL8, regulate lipoprotein lipase (LPL) activity.
      Deficiency in either ANGPTL3 or ANGPTL8 reduces plasma triglyceride levels and
      increases LPL activity, whereas overexpression of either protein does the
      opposite. Recent studies suggest that ANGPTL8 may functionally interact with
      ANGPTL3 to alter clearance of plasma triglycerides; however, the nature of this
      interaction has remained elusive. We tested the hypothesis that ANGPTL8 forms a
      complex with ANGPTL3 and that this complex is necessary for the inhibition of
      vascular LPL by ANGPTL3. METHODS: We analyzed the interactions of ANGPTL3 and
      ANGPTL8 with each other and with LPL using co-immunoprecipitation, western
      blotting, lipase activity assays, and the NanoBiT split-luciferase system. We
      also used adenovirus injection to overexpress ANGPTL3 in mice that lacked
      ANGPTL8. RESULTS: We found that ANGPTL3 or ANGPTL8 alone could only inhibit LPL
      at concentrations that far exceeded physiological levels, especially when LPL was
      bound to its endothelial cell receptor/transporter GPIHBP1
      (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein
      1). Physical interaction was observed between ANGPTL3 and ANGPTL8 when the
      proteins were co-expressed, and co-expression with ANGPTL3 greatly enhanced the
      secretion of ANGPTL8. Importantly, ANGPTL3-ANGPTL8 complexes had a dramatically
      increased ability to inhibit LPL compared to either protein alone. Adenovirus
      experiments showed that 2-fold overexpression of ANGPTL3 significantly increased
      plasma triglycerides only in the presence of ANGPTL8. Protein interaction assays
      showed that ANGPTL8 greatly increased the ability of ANGPTL3 to bind LPL.
      CONCLUSIONS: Together, these data indicate that ANGPTL8 binds to ANGPTL3 and that
      this complex is necessary for ANGPTL3 to efficiently bind and inhibit LPL.

PMID- 29031716
TI  - Adipocyte glucocorticoid receptor is important in lipolysis and insulin
      resistance due to exogenous steroids, but not insulin resistance caused by high
      fat feeding.
AB  - OBJECTIVE: The critical role of adipose tissue in energy and nutrient homeostasis
      is influenced by many external factors, including overnutrition, inflammation,
      and exogenous hormones. Prior studies have suggested that glucocorticoids (GCs)
      in particular are major drivers of physiological and pathophysiological changes
      in adipocytes. In order to determine whether these effects directly require the
      glucocorticoid receptor (GR) within adipocytes, we generated adipocyte-specific
      GR knockout (AGRKO) mice. METHODS: AGRKO and control mice were fed chow or high
      fat diet (HFD) for 14 weeks. Alternatively, AGRKO and control mice were injected
      with dexamethasone for two months. Glucose tolerance, insulin sensitivity,
      adiposity, lipolysis, thermogenesis, and insulin signaling were assessed.
      RESULTS: We find that obesity, insulin resistance, and dysglycemia associated
      with high fat feeding do not require an intact GR in the adipocyte. However,
      exogenous dexamethasone (Dex) promotes metabolic dysfunction in mice, and this
      effect is reduced in mice lacking GR in adipocytes. The ability of Dex to promote
      "whitening" of brown fat is also reduced in these animals. We also show that GR
      is required for beta-adrenergic and cold stimulation-mediated lipolysis via
      expression of the key lipolytic enzyme ATGL. CONCLUSIONS: Our data suggest that
      the GR plays a role in normal adipose physiology via effects on lipolysis and
      mediates at least some of the adverse effects of exogenous steroids on metabolic
      function. The data also indicate that intra-adipocyte GR plays less of a role
      than previously believed in the local and systemic pathology associated with
      overnutrition.

PMID- 29031717
TI  - Lipid nanoparticle delivery of glucagon receptor siRNA improves glucose
      homeostasis in mouse models of diabetes.
AB  - OBJECTIVE: Hyperglucagonemia is present in many forms of diabetes and contributes
      to hyperglycemia, and glucagon suppression can ameliorate diabetes in mice.
      Leptin, a glucagon suppressor, can also reverse diabetes in rodents. Lipid
      nanoparticle (LNP) delivery of small interfering RNA (siRNA) effectively targets
      the liver and is in clinical trials for the treatment of various diseases. We
      compared the effectiveness of glucagon receptor (Gcgr)-siRNA delivered via LNPs
      to leptin in two mouse models of diabetes. METHODS: Gcgr siRNA encapsulated into
      LNPs or leptin was administered to mice with diabetes due to injection of the
      beta-cell toxin streptozotocin (STZ) alone or combined with high fat diet
      (HFD/STZ). RESULTS: In STZ-diabetic mice, a single injection of Gcgr siRNA
      lowered blood glucose levels for 3 weeks, improved glucose tolerance, and
      normalized plasma ketones levels, while leptin therapy normalized blood glucose
      levels, oral glucose tolerance, and plasma ketones, and suppressed lipid
      metabolism. In contrast, in HFD/STZ-diabetic mice, Gcgr siRNA lowered blood
      glucose levels for 2 months, improved oral glucose tolerance, and reduced HbA1c,
      while leptin had no beneficial effects. CONCLUSIONS: While leptin may be more
      effective than Gcgr siRNA at normalizing both glucose and lipid metabolism in STZ
      diabetes, Gcgr siRNA is more effective at reducing blood glucose levels in
      HFD/STZ diabetes.

PMID- 29031718
TI  - Galphas regulates Glucagon-Like Peptide 1 Receptor-mediated cyclic AMP generation
      at Rab5 endosomal compartment.
AB  - OBJECTIVE: Upon activation, G protein coupled receptors (GPCRs) associate with
      heterotrimeric G proteins at the plasma membrane to initiate second messenger
      signaling. Subsequently, the activated receptor experiences desensitization,
      internalization, and recycling back to the plasma membrane, or it undergoes
      lysosomal degradation. Recent reports highlight specific cases of persistent
      cyclic AMP generation by internalized GPCRs, although the functional significance
      and mechanistic details remain to be defined. Cyclic AMP generation from
      internalized Glucagon-Like Peptide-1 Receptor (GLP-1R) has previously been
      reported from our laboratory. This study aimed at deciphering the molecular
      mechanism by which internalized GLP-R supports sustained cyclic AMP generation
      upon receptor activation in pancreatic beta cells. METHODS: We studied the time
      course of cyclic AMP generation following GLP-1R activation with particular
      emphasis on defining the location where cyclic AMP is generated. Detection
      involved a novel GLP-1 conjugate coupled with immunofluorescence using specific
      endosomal markers. Finally, we employed co-immunoprecipitation as well as
      immunofluorescence to assess the protein-protein interactions that regulate GLP
      1R mediated cyclic AMP generation at endosomes. RESULTS: Our data reveal that
      prolonged association of G protein alpha subunit Galphas with activated GLP-1R
      contributed to sustained cyclic AMP generation at Rab 5 endosomal compartment.
      CONCLUSIONS: The findings provide the mechanism of endosomal cyclic AMP
      generation following GLP-1R activation. We identified the specific compartment
      that serves as an organizing center to generate endosomal cyclic AMP by
      internalized activated receptor complex.

PMID- 29031719
TI  - Macrophage alternative activation confers protection against lipotoxicity-induced
      cell death.
AB  - OBJECTIVE: Alternative activation (M2) of adipose tissue resident macrophage
      (ATM) inhibits obesity-induced metabolic inflammation. The underlying mechanisms
      remain unclear. Recent studies have shown that dysregulated lipid homeostasis
      caused by increased lipolysis in white adipose tissue (WAT) in the obese state is
      a trigger of inflammatory responses. We investigated the role of M2 macrophages
      in lipotoxicity-induced inflammation. METHODS: We used microarray experiments to
      profile macrophage gene expression regulated by two M2 inducers, interleukin-4
      (Il-4), and peroxisome proliferator-activated receptor delta/gamma
      (Ppardelta/Ppargamma) agonists. Functional validation studies were performed in
      bone marrow-derived macrophages and mice deprived of the signal transducer and
      activator of transcription 6 gene (Stat6; downstream effector of Il-4) or
      Ppardelta/Ppargamma genes (downstream effectors of Stat6). Palmitic acid (PA) and
      beta-adrenergic agonist were employed to induce macrophage lipid loading in vitro
      and in vivo, respectively. RESULTS: Profiling of genes regulated by Il-4 or
      Ppardelta/Ppargamma agonists reveals that alternative activation promotes the
      cell survival program, while inhibiting that of inflammation-related cell death.
      Deletion of Stat6 or Ppardelta/Ppargamma increases the susceptibility of
      macrophages to PA-induced cell death. NLR family pyrin domain containing 3
      (Nlrp3) inflammasome activation by PA in the presence of lipopolysaccharide is
      also increased in Stat6-/- macrophages and to a lesser extent, in Ppardelta/gamma
      /- macrophages. In concert, beta-adrenergic agonist-induced lipolysis results in
      higher levels of cell death and inflammatory markers in ATMs derived from myeloid
      specific Ppardelta/gamma-/- or Stat6-/- mice. CONCLUSIONS: Our data suggest that
      ATM cell death is closely linked to metabolic inflammation. Within WAT where
      concentrations of free fatty acids fluctuate, M2 polarization regulated by the
      Stat6-Ppar axis enhances ATM's tolerance to lipid-mediated stress, thereby
      maintaining the homeostatic state.

PMID- 29031720
TI  - Brown adipocytes can display a mammary basal myoepithelial cell phenotype in
      vivo.
AB  - OBJECTIVE: Previous work has suggested that white adipocytes may also show a
      mammary luminal secretory cell phenotype during lactation. The capacity of brown
      and beige/brite adipocytes to display a mammary cell phenotype and the levels at
      which they demonstrate such phenotypes in vivo is currently unknown. METHODS: To
      investigate the putative adipocyte origin of mammary gland cells, we performed
      genetic lineage-labeling experiments in BAT and the mammary glands. RESULTS:
      These studies indicated that the classic brown adipocytes (Ucp1+) and
      subcutaneous beige/brite adipocytes (Ucp1-/+) were found in the mammary gland
      during lactation, when they exhibited a mammary myoepithelial phenotype. Up to
      2.5% of the anterior dorsal interscapular mammary myoepithelial cell population
      had a brown adipocyte origin with an adipose and myoepithelial gene signature
      during lactation. Eliminating these cells, along with all the brown adipocytes,
      significantly slowed offspring growth, potentially demonstrating their functional
      importance. Additionally, we showed mammary epithelial lineage Mmtv+ and Krt14+
      cells expressed brown adipocyte markers after weaning, demonstrating that mammary
      gland cells can display an adipose phenotype. CONCLUSIONS: The identification of
      a brown adipocyte origin of mammary myoepithelial cells provides a novel
      perspective on the interrelationships between adipocytes and mammary cells with
      implications for our understanding of obesity and breast cancer.

PMID- 29031721
TI  - Cdkal1, a type 2 diabetes susceptibility gene, regulates mitochondrial function
      in adipose tissue.
AB  - OBJECTIVES: Understanding how loci identified by genome wide association studies
      (GWAS) contribute to pathogenesis requires new mechanistic insights. Variants
      within CDKAL1 are strongly linked to an increased risk of developing type 2
      diabetes and obesity. Investigations in mouse models have focused on the function
      of Cdkal1 as a tRNALys modifier and downstream effects of Cdkal1 loss on pro
      insulin translational fidelity in pancreatic beta-cells. However, Cdkal1 is
      broadly expressed in other metabolically relevant tissues, including adipose
      tissue. In addition, the Cdkal1 homolog Cdk5rap1 regulates mitochondrial protein
      translation and mitochondrial function in skeletal muscle. We tested whether
      adipocyte-specific Cdkal1 deletion alters systemic glucose homeostasis or adipose
      mitochondrial function independently of its effects on pro-insulin translation
      and insulin secretion. METHODS: We measured mRNA levels of type 2 diabetes GWAS
      genes, including Cdkal1, in adipose tissue from lean and obese mice. We then
      established a mouse model with adipocyte-specific Cdkal1 deletion. We examined
      the effects of adipose Cdkal1 deletion using indirect calorimetry on mice during
      a cold temperature challenge, as well as by measuring cellular and mitochondrial
      respiration in vitro. We also examined brown adipose tissue (BAT) mitochondrial
      morphology by electron microscopy. Utilizing co-immunoprecipitation followed by
      mass spectrometry, we performed interaction mapping to identify new CDKAL1
      binding partners. Furthermore, we tested whether Cdkal1 loss in adipose tissue
      affects total protein levels or accurate Lys incorporation by tRNALys using
      quantitative mass spectrometry. RESULTS: We found that Cdkal1 mRNA levels are
      reduced in adipose tissue of obese mice. Using adipose-specific Cdkal1 KO mice (A
      KO), we demonstrated that mitochondrial function is impaired in primary
      differentiated brown adipocytes and in isolated mitochondria from A-KO brown
      adipose tissue. A-KO mice displayed decreased energy expenditure during 4 
      degrees C cold challenge. Furthermore, mitochondrial morphology was highly
      abnormal in A-KO BAT. Surprisingly, we found that lysine codon representation was
      unchanged in Cdkal1 A-KO adipose tissue. We identified novel protein interactors
      of CDKAL1, including SLC25A4/ANT1, an inner mitochondrial membrane ADP/ATP
      translocator. ANT proteins can account for the UCP1-independent basal proton leak
      in BAT mitochondria. Cdkal1 A-KO mice had increased ANT1 protein levels in their
      white adipose tissue. CONCLUSIONS: Cdkal1 is necessary for normal mitochondrial
      morphology and function in adipose tissue. These results suggest that the type 2
      diabetes susceptibility gene CDKAL1 has novel functions in regulating
      mitochondrial activity.

PMID- 29031723
TI  - Inhibition of cholinergic potentiation of insulin secretion from pancreatic
      islets by chronic elevation of glucose and fatty acids: Protection by casein
      kinase 2 inhibitor.
AB  - OBJECTIVES: Chronic hyperlipidemia and hyperglycemia are characteristic features
      of type 2 diabetes (T2DM) that are thought to cause or contribute to beta-cell
      dysfunction by "glucolipotoxicity." Previously we have shown that acute treatment
      of pancreatic islets with fatty acids (FA) decreases acetylcholine-potentiated
      insulin secretion. This acetylcholine response is mediated by M3 muscarinic
      receptors, which play a key role in regulating beta-cell function. Here we
      examine whether chronic FA exposure also inhibits acetylcholine-potentiated
      insulin secretion using mouse and human islets. METHODS: Islets were cultured for
      3 or 4 days at different glucose concentration with 0.5 mM palmitic acid (PA) or
      a 2:1 mixture of PA and oleic acid (OA) at 1% albumin (PA/BSA molar ratio 3.3).
      Afterwards, the response to glucose and acetylcholine were studied in perifusion
      experiments. RESULTS: FA-induced impairment of insulin secretion and Ca2+
      signaling depended strongly on the glucose concentrations of the culture medium.
      PA and OA in combination reduced acetylcholine potentiation of insulin secretion
      more than PA alone, both in mouse and human islets, with no evidence of a
      protective role of OA. In contrast, lipotoxicity was not observed with islets
      cultured for 3 days in medium containing less than 1 mM glucose and a mixture of
      glutamine and leucine (7 mM each). High glucose and FAs reduced endoplasmic
      reticulum (ER) Ca2+ storage capacity; however, preserving ER Ca2+ by blocking the
      IP3 receptor with xestospongin C did not protect islets from glucolipotoxic
      effects on insulin secretion. In contrast, an inhibitor of casein kinase 2 (CK2)
      protected the glucose dependent acetylcholine potentiation of insulin secretion
      in mouse and human islets against glucolipotoxicity. CONCLUSIONS: These results
      show that chronic FA treatment decreases acetylcholine potentiation of insulin
      secretion and that this effect is strictly glucose dependent and might involve
      CK2 phosphorylation of beta-cell M3 muscarinic receptors.

PMID- 29031724
TI  - Elevated hepatic DPP4 activity promotes insulin resistance and non-alcoholic
      fatty liver disease.
AB  - OBJECTIVE: Increased hepatic expression of dipeptidyl peptidase 4 (DPP4) is
      associated with non-alcoholic fatty liver disease (NAFLD). Whether this is
      causative for the development of NAFLD is not yet clarified. Here we investigate
      the effect of hepatic DPP4 overexpression on the development of liver steatosis
      in a mouse model of diet-induced obesity. METHODS: Plasma DPP4 activity of
      subjects with or without NAFLD was analyzed. Wild-type (WT) and liver-specific
      Dpp4 transgenic mice (Dpp4-Liv-Tg) were fed a high-fat diet and characterized for
      body weight, body composition, hepatic fat content and insulin sensitivity. In
      vitro experiments on HepG2 cells and primary mouse hepatocytes were conducted to
      validate cell autonomous effects of DPP4 on lipid storage and insulin
      sensitivity. RESULTS: Subjects suffering from insulin resistance and NAFLD show
      an increased plasma DPP4 activity when compared to healthy controls. Analysis of
      Dpp4-Liv-Tg mice revealed elevated systemic DPP4 activity and diminished active
      GLP-1 levels. They furthermore show increased body weight, fat mass, adipose
      tissue inflammation, hepatic steatosis, liver damage and hypercholesterolemia.
      These effects were accompanied by increased expression of PPARgamma and CD36 as
      well as severe insulin resistance in the liver. In agreement, treatment of HepG2
      cells and primary hepatocytes with physiological concentrations of DPP4 resulted
      in impaired insulin sensitivity independent of lipid content. CONCLUSIONS: Our
      results give evidence that elevated expression of DPP4 in the liver promotes
      NAFLD and insulin resistance. This is linked to reduced levels of active GLP-1,
      but also to auto- and paracrine effects of DPP4 on hepatic insulin signaling.

PMID- 29031722
TI  - Activated macrophages control human adipocyte mitochondrial bioenergetics via
      secreted factors.
AB  - OBJECTIVE: Obesity-associated WAT inflammation is characterized by the
      accumulation and local activation of macrophages (MPhis), and recent data from
      mouse studies suggest that macrophages are modifiers of adipocyte energy
      metabolism and mitochondrial function. As mitochondrial dysfunction has been
      associated with obesity and the metabolic syndrome in humans, herein we aimed to
      delineate how human macrophages may affect energy metabolism of white adipocytes.
      METHODS: Human adipose tissue gene expression analysis for markers of macrophage
      activation and tissue inflammation (CD11c, CD40, CD163, CD206, CD80, MCP1,
      TNFalpha) in relationship to mitochondrial complex I (NDUFB8) and complex III
      (UQCRC2) was performed on subcutaneous WAT of 24 women (BMI 20-61 kg/m2). Guided
      by these results, the impact of secreted factors of LPS/IFNgamma- and
      IL10/TGFbeta-activated human macrophages (THP1, primary blood-derived) on
      mitochondrial function in human subcutaneous white adipocytes (SGBS, primary) was
      determined by extracellular flux analysis (Seahorse technology) and gene/protein
      expression. RESULTS: Stepwise regression analysis of human WAT gene expression
      data revealed that a linear combination of CD40 and CD163 was the strongest
      predictor for mitochondrial complex I (NDUFB8) and complex III (UQCRC2) levels,
      independent of BMI. IL10/TGFbeta-activated MPhis displayed high CD163 and low
      CD40 expression and secreted factors that decreased UQCRC2 gene/protein
      expression and ATP-linked respiration in human white adipocytes. In contrast,
      LPS/IFNgamma-activated MPhis showed high CD40 and low CD163 expression and
      secreted factors that enhanced adipocyte mitochondrial activity resulting in a
      total difference of 37% in ATP-linked respiration of white adipocytes (p =
      0.0024) when comparing the effect of LPS/IFNgamma- vs IL10/TGFbeta-activated
      MPhis. CONCLUSION: Our data demonstrate that macrophages modulate human adipocyte
      energy metabolism via an activation-dependent paracrine mechanism.

PMID- 29031725
TI  - Intestinal SIRT3 overexpression in mice improves whole body glucose homeostasis
      independent of body weight.
AB  - OBJECTIVE: Intestinal metabolism might play a greater role in regulating whole
      body metabolism than previously believed. We aimed to enhance enterocyte
      metabolism in mice and investigate if it plays a role in diet-induced obesity
      (DIO) and its comorbidities. METHODS: Using the cre-loxP system, we overexpressed
      the mitochondrial NAD+ dependent protein deacetylase SIRT3 in enterocytes of mice
      (iSIRT3 mice). We chronically fed iSIRT3 mice and floxed-SIRT3 control (S3fl)
      mice a low-fat, control diet (CD) or a high-fat diet (HFD) and then phenotyped
      the mice. RESULTS: There were no genotype differences in any of the parameters
      tested when the mice were fed CD. Also, iSIRT3 mice were equally susceptible to
      the development of DIO as S3fl mice when fed HFD. They were, however, better able
      than S3fl mice to regulate their blood glucose levels in response to exogenous
      insulin and glucose, indicating that they were protected from developing insulin
      resistance. This improved glucose homeostasis was accompanied by an increase in
      enterocyte metabolic activity and an upregulation of ketogenic gene expression in
      the small intestine. CONCLUSION: Enhancing enterocyte oxidative metabolism can
      improve whole body glucose homeostasis.

PMID- 29031726
TI  - Reduced renal sympathetic nerve activity contributes to elevated glycosuria and
      improved glucose tolerance in hypothalamus-specific Pomc knockout mice.
AB  - OBJECTIVE: Hypothalamic arcuate nucleus-specific pro-opiomelanocortin deficient
      (ArcPomc-/-) mice exhibit improved glucose tolerance despite massive obesity and
      insulin resistance. We demonstrated previously that their improved glucose
      tolerance is due to elevated glycosuria. However, the underlying mechanisms that
      link glucose reabsorption in the kidney with ArcPomc remain unclear. Given the
      function of the hypothalamic melanocortin system in controlling sympathetic
      outflow, we hypothesized that reduced renal sympathetic nerve activity (RSNA) in
      ArcPomc-/- mice could explain their elevated glycosuria and consequent enhanced
      glucose tolerance. METHODS: We measured RSNA by multifiber recording directly
      from the nerves innervating the kidneys in ArcPomc-/- mice. To further validate
      the function of RSNA in glucose reabsorption, we denervated the kidneys of WT and
      diabetic db/db mice before measuring their glucose tolerance and urine glucose
      levels. Moreover, we performed western blot and immunohistochemistry to determine
      kidney GLUT2 and SGLT2 levels in either ArcPomc-/- mice or the renal-denervated
      mice. RESULTS: Consistent with our hypothesis, we found that basal RSNA was
      decreased in ArcPomc-/- mice relative to their wild type (WT) littermates.
      Remarkably, both WT and db/db mice exhibited elevated glycosuria and improved
      glucose tolerance after renal denervation. The elevated glycosuria in obese
      ArcPomc-/-, WT and db/db mice was due to reduced renal GLUT2 levels in the
      proximal tubules. Overall, we show that renal-denervated WT and diabetic mice
      recapitulate the phenotype of improved glucose tolerance and elevated glycosuria
      associated with reduced renal GLUT2 levels observed in obese ArcPomc-/- mice.
      CONCLUSION: Hence, we conclude that ArcPomc is essential in maintaining basal
      RSNA and that elevated glycosuria is a possible mechanism to explain improved
      glucose tolerance after renal denervation in drug resistant hypertensive
      patients.

PMID- 29031727
TI  - Angiopoietin-like protein 4 is an exercise-induced hepatokine in humans,
      regulated by glucagon and cAMP.
AB  - OBJECTIVE: Angiopoietin-like protein-4 (ANGPTL4) is a circulating protein that is
      highly expressed in liver and implicated in regulation of plasma triglyceride
      levels. Systemic ANGPTL4 increases during prolonged fasting and is suggested to
      be secreted from skeletal muscle following exercise. METHODS: We investigated the
      origin of exercise-induced ANGPTL4 in humans by measuring the arterial-to-venous
      difference over the leg and the hepato-splanchnic bed during an acute bout of
      exercise. Furthermore, the impact of the glucagon-to-insulin ratio on plasma
      ANGPTL4 was studied in healthy individuals. The regulation of ANGPTL4 was
      investigated in both hepatic and muscle cells. RESULTS: The hepato-splanchnic
      bed, but not the leg, contributed to exercise-induced plasma ANGPTL4. Further
      studies using hormone infusions revealed that the glucagon-to-insulin ratio is an
      important regulator of plasma ANGPTL4 as elevated glucagon in the absence of
      elevated insulin increased plasma ANGPTL4 in resting subjects, whereas infusion
      of somatostatin during exercise blunted the increase of both glucagon and
      ANGPTL4. Moreover, activation of the cAMP/PKA signaling cascade let to an
      increase in ANGPTL4 mRNA levels in hepatic cells, which was prevented by
      inhibition of PKA. In humans, muscle ANGPTL4 mRNA increased during fasting, with
      only a marginal further induction by exercise. In human muscle cells, no
      inhibitory effect of AMPK activation could be demonstrated on ANGPTL4 expression.
      CONCLUSIONS: The data suggest that exercise-induced ANGPTL4 is secreted from the
      liver and driven by a glucagon-cAMP-PKA pathway in humans. These findings link
      the liver, insulin/glucagon, and lipid metabolism together, which could implicate
      a role of ANGPTL4 in metabolic diseases.

PMID- 29031728
TI  - Single-cell RNA-sequencing reveals a distinct population of proglucagon
      expressing cells specific to the mouse upper small intestine.
AB  - OBJECTIVES: To identify sub-populations of intestinal preproglucagon-expressing
      (PPG) cells producing Glucagon-like Peptide-1, and their associated expression
      profiles of sensory receptors, thereby enabling the discovery of therapeutic
      strategies that target these cell populations for the treatment of diabetes and
      obesity. METHODS: We performed single cell RNA sequencing of PPG-cells purified
      by flow cytometry from the upper small intestine of 3 GLU-Venus mice. Cells from
      2 mice were sequenced at low depth, and from the third mouse at high depth. High
      quality sequencing data from 234 PPG-cells were used to identify clusters by tSNE
      analysis. qPCR was performed to compare the longitudinal and crypt/villus
      locations of cluster-specific genes. Immunofluorescence and mass spectrometry
      were used to confirm protein expression. RESULTS: PPG-cells formed 3 major
      clusters: a group with typical characteristics of classical L-cells, including
      high expression of Gcg and Pyy (comprising 51% of all PPG-cells); a cell type
      overlapping with Gip-expressing K-cells (14%); and a unique cluster expressing
      Tph1 and Pzp that was predominantly located in proximal small intestine villi and
      co-produced 5-HT (35%). Expression of G-protein coupled receptors differed
      between clusters, suggesting the cell types are differentially regulated and
      would be differentially targetable. CONCLUSIONS: Our findings support the
      emerging concept that many enteroendocrine cell populations are highly
      overlapping, with individual cells producing a range of peptides previously
      assigned to distinct cell types. Different receptor expression profiles across
      the clusters highlight potential drug targets to increase gut hormone secretion
      for the treatment of diabetes and obesity.

PMID- 29031729
TI  - Point mutation of Ffar1 abrogates fatty acid-dependent insulin secretion, but
      protects against HFD-induced glucose intolerance.
AB  - OBJECTIVE: The fatty acid receptor 1 (FFAR1/GPR40) mediates fatty acid-dependent
      augmentation of glucose-induced insulin secretion (GIIS) in pancreatic beta
      cells. Genetically engineered Ffar1-knockout/congenic mice univocally displayed
      impaired fatty acid-mediated insulin secretion, but in vivo experiments delivered
      controversial results regarding the function of FFAR1 in glucose homeostasis and
      liver steatosis. This study presents a new coisogenic mouse model carrying a
      point mutation in Ffar1 with functional consequence. These mice reflect the
      situations in humans in which point mutations can lead to protein malfunction and
      disease development. METHODS: The Munich N-ethyl-N-nitrosourea (ENU) mutagenesis
      derived F1 archive containing over 16,800 sperms and corresponding DNA samples
      was screened for mutations in the coding region of Ffar1. Two missense mutations
      (R258W and T146S) in the extracellular domain of the protein were chosen and
      homozygote mice were generated. The functional consequence of these mutations was
      examined in vitro in isolated islets and in vivo in chow diet and high fat diet
      fed mice. RESULTS: Palmitate, 50 MUM, and the FFAR1 agonist TUG-469, 3 MUM,
      stimulated insulin secretion in islets of Ffar1T146S/T146S mutant mice and of
      wild-type littermates, while in islets of Ffar1R258W/R258W mutant mice, these
      stimulatory effects were abolished. Insulin content and mRNA levels of Ffar1,
      Glp1r, Ins2, Slc2a2, Ppara, and Ppard were not significantly different between
      wild-type and Ffar1R258W/R258W mouse islets. Palmitate exposure, 600 MUM,
      significantly increased Ppara mRNA levels in wild-type but not in
      Ffar1R258W/R258W mouse islets. On the contrary, Slc2a2 mRNA levels were
      significantly reduced in both wild-type and Ffar1R258W/R258W mouse islets after
      palmitate treatment. HFD feeding induced glucose intolerance in wild-type mice.
      Ffar1R258W/R258W mutant mice remained glucose tolerant although their body weight
      gain, liver steatosis, insulin resistance, and plasma insulin levels were not
      different from those of wild-type littermates. Worth mentioning, fasting plasma
      insulin levels were lower in Ffar1R258W/R258W mice. CONCLUSION: A point mutation
      in Ffar1 abrogates the stimulatory effect of palmitate on GIIS, an effect that
      does not necessarily translate to HFD-induced glucose intolerance.

PMID- 29031730
TI  - Bidirectional manipulation of gene expression in adipocytes using CRISPRa and
      siRNA.
AB  - OBJECTIVE: Functional investigation of novel gene/protein targets associated with
      adipocyte differentiation or function heavily relies on efficient and accessible
      tools to manipulate gene expression in adipocytes in vitro. Recent advances in
      gene-editing technologies such as CRISPR-Cas9 have not only eased gene editing
      but also greatly facilitated modulation of gene expression without altering the
      genome. Here, we aimed to develop and validate a competent in vitro adipocyte
      model of controllable functionality as well as multiplexed gene manipulation in
      adipocytes, using the CRISPRa "SAM" system and siRNAs to simultaneously
      overexpress and silence selected genes in the same cell populations. METHODS: We
      introduced a stable expression of dCas9-VP64 and MS2-P65, the core components of
      the CRIPSRa SAM system, in mesenchymal C3H/10T1/2 cells through viral delivery
      and used guide RNAs targeting Ppargamma2, Prdm16, Zfp423, or Ucp1 to control the
      expression of key genes involved in adipocyte differentiation and function. We
      additionally co-transfected mature adipocytes with sgRNA plasmids and siRNA to
      simultaneously up-regulate and silence selected genes. Quantitative gene
      expression, oxygen consumption, fluorescence-activated cell sorting and
      immunocytochemistry served as validation proxies in pre- or mature adipocytes.
      RESULTS: CRISPRa SAM-mediated up-regulation of a key adipogenic gene, Ppargamma2,
      was successfully achieved using selected sgRNAs targeting the Ppargamma2 promoter
      region (i.e. up to 104 fold); this induction was long lasting and sufficient to
      promote adipogenesis. Furthermore, co-activation of Ppargamma2 with either Prdm16
      or Zfp423 transcripts drove distinct thermogenic gene expression patterns
      associated with increased or decreased oxygen consumption, respectively,
      mimicking typical characteristics of brite/beige or white cell lineages. Lastly,
      we demonstrated that up-regulation of endogenous genes in mature adipocytes was
      also easily and efficiently achieved using CRISPRa SAM, here exemplified by
      targeted Ucp1 overexpression (up to 4 * 103 fold), and that it was compatible
      with concomitant gene silencing using siRNA, allowing for bidirectional
      manipulation of gene expression in the same cell populations. CONCLUSIONS: We
      demonstrate that the CRISPRa SAM system can be easily adopted and used to
      efficiently manipulate gene expression in pre- and mature adipocytes in vitro.
      Moreover, we describe a novel methodological approach combining the activation of
      endogenous genes and siRNA-mediated gene silencing, thus providing a powerful
      tool to functionally decipher genetic factors controlling adipogenesis and
      adipocyte functions.

PMID- 29031731
TI  - Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R
      deficiency.
AB  - OBJECTIVE: Pro-opiomelanocortin (POMC)-derived peptides act on neurons expressing
      the Melanocortin 4 receptor (MC4R) to reduce body weight. Setmelanotide is a
      highly potent MC4R agonist that leads to weight loss in diet-induced obese
      animals and in obese individuals with complete POMC deficiency. While POMC
      deficiency is very rare, 1-5% of severely obese individuals harbor heterozygous
      mutations in MC4R. We sought to assess the efficacy of Setmelanotide in human
      MC4R deficiency. METHODS: We studied the effects of Setmelanotide on mutant MC4Rs
      in cells and the weight loss response to Setmelanotide administration in rodent
      studies and a human clinical trial. We annotated the functional status of 369
      published MC4R variants. RESULTS: In cells, we showed that Setmelanotide is
      significantly more potent at MC4R than the endogenous ligand alpha-melanocyte
      stimulating hormone and can disproportionally rescue signaling by a subset of
      severely impaired MC4R mutants. Wild-type rodents appear more sensitive to
      Setmelanotide when compared to MC4R heterozygous deficient mice, while MC4R
      knockout mice fail to respond. In a 28-day Phase 1b clinical trial, Setmelanotide
      led to weight loss in obese MC4R variant carriers. Patients with POMC defects
      upstream of MC4R show significantly more weight loss with Setmelanotide than MC4R
      deficient patients or obese controls. CONCLUSIONS: Setmelanotide led to weight
      loss in obese people with MC4R deficiency; however, further studies are justified
      to establish whether Setmelanotide can elicit clinically meaningful weight loss
      in a subset of the MC4R deficient obese population.

PMID- 29031732
TI  - Neonatal pancreatic pericytes support beta-cell proliferation.
AB  - OBJECTIVE: The maintenance and expansion of beta-cell mass rely on their
      proliferation, which reaches its peak in the neonatal stage. beta-cell
      proliferation was found to rely on cells of the islet microenvironment. We
      hypothesized that pericytes, which are components of the islet vasculature,
      support neonatal beta-cell proliferation. METHODS: To test our hypothesis, we
      combined in vivo and in vitro approaches. Briefly, we used a Diphtheria toxin
      based transgenic mouse system to specifically deplete neonatal pancreatic
      pericytes in vivo. We further cultured neonatal pericytes isolated from the
      neonatal pancreas and combined the use of a beta-cell line and primary cultured
      mouse beta-cells. RESULTS: Our findings indicate that neonatal pancreatic
      pericytes are required and sufficient for beta-cell proliferation. We observed
      impaired proliferation of neonatal beta-cells upon in vivo depletion of
      pancreatic pericytes. Furthermore, exposure to pericyte-conditioned medium
      stimulated proliferation in cultured beta-cells. CONCLUSIONS: This study
      introduces pancreatic pericytes as regulators of neonatal beta-cell
      proliferation. In addition to advancing current understanding of the
      physiological beta-cell replication process, these findings could facilitate the
      development of protocols aimed at expending these cells as a potential cure for
      diabetes.

PMID- 29031733
TI  - Prognostic outcomes in advanced breast cancer: the metastasis-free interval is
      important.
AB  - Metastatic breast cancer is a heterogeneous disease with a diverse clinical
      course. There have been limited studies regarding prognostic outcomes in patients
      with de novo metastatic breast cancer versus those with metastatic recurrence,
      with controversial observations. In this study, we sought to examine the
      difference in survival outcomes among patients with advanced breast cancer
      stratified based on metastasis-free interval (MFI) and to further explore the
      role of systemic therapy in these patient groups. Of 569 consecutive patients
      with stage IV breast cancer between 1998 and 2013, 201 had de novo metastatic
      disease (metastasis at diagnosis) and 368 developed metastatic recurrence,
      including 168 with an MFI<=24 months and 200 with an MFI>24 months. In the 492
      patients who received systemic therapy, de novo metastasis was an independent
      favorable prognostic factor for overall survival after metastasis when compared
      with metastatic recurrence irrespective of MFI. Compared with the patients with
      metastatic recurrence with an MFI<=24 months, those with an MFI>24 months had a
      superior survival outcome, although it did not reach statistical significance by
      multivariate analysis. In contrast, de novo metastatic breast cancer was
      associated with a worse prognosis when compared with recurring metastasis in the
      patients who did not receive systemic treatment. These findings provide more
      insight into the natural history of advanced breast cancer, thus necessitating
      further investigation into the molecular mechanism of drug resistance.

PMID- 29031734
TI  - Residual NO modulates contractile responses and membrane potential in isolated
      rat mesenteric arteries.
AB  - Shear stress or vasocontriction causes endothelial nitric oxide (NO) release
      resulting in the regulation of vascular smooth muscle tone in small resistance
      arteries. Generation of NO is inhibited by nitric oxide synthase (NOS)
      inhibitors. In this study, we investigated the effect of residual NO, released
      even in the presence of NOS inhibitors, on the membrane depolarization and
      phenylephrine-induced contractions of smooth muscle. For this purpose, we used
      hydroxocobalamin (HC), an NO scavenger, in the presence of NOS inhibitiors,
      Nomega-nitro- L-arginine (L-NA) or Nomega-nitro-L-arginine methyl ester (L-NAME)
      in mesenteric arteries isolated from rats. Phenylephrine (0,01-10 MUM), an alpha1
      adrenoceptor agonist, led to depolarisation and concentration-dependent
      contraction in mesenteric arteries. The depolarisation and contractile responses
      were augmented by L-NA or L-NAME. Hydroxocobalamine (HC) or carboxy-PTIO (c-PTIO)
      also caused to further increase the membrane depolarization and contractions
      induced by phenylephrine in the presence of NOS inhibitors. Chemical removal of
      endothelium by saponin, tyrosin kinase inhibitor erbstatin A, but not calmodulin
      inhibitor calmidazolium inhibited the additional membrane depolarisation and
      contractile responses induced by L-NA or L-NAME and L-NA or L-NAME plus HC. These
      findings show that residual NO modulates the contractile responses in isolated
      rat mesenteric arteries by exerting a tonic inhibitor effect on the
      depolarization and vasoconstriction induced by phenylephrine.

PMID- 29031735
TI  - The temporal expression profile of a Nos3-related natural antisense RNA in the
      brain suggests a possible role in neurogenesis.
AB  - Experimental work over the past several years has revealed an unexpected
      abundance of long natural antisense transcripts (NATs) in eukaryotic species. In
      light of the proposed role of such RNA molecules in the regulation of gene
      expression in the brain, attention is now focused on specific examples of
      neuronal NATs. Of particular interest are NATs that are complementary to mRNAs
      encoding nitric oxide synthase (NOS), the enzyme responsible for production of
      the important gaseous neurotransmitter nitric oxide (NO). Here we study the
      temporal expression profile of murine Nos3as NAT in the brain. Notably, Nos3as
      NAT is known to act as a negative regulator of Nos3 gene expression. The results
      of our quantitative analysis reveal differential expression of Nos3as NAT during
      embryonic and post-embryonic stages of development of the brain. Also, they show
      that the low levels of Nos3as NAT coincides with active neurogenesis. In addition
      we report on an inverse correlation between the relative expression level of
      Nos3as NAT and the level of Nos3 protein. Thus our data raise the hypothesis that
      the Nos3as NAT regulates neurogenesis through suppression of Nos3 gene activity.
      This idea is further supported by experiments conducted on the olfactory bulbs
      and cultured neuroblastoma cells.

PMID- 29031736
TI  - Livestock ownership and microbial contamination of drinking-water: Evidence from
      nationally representative household surveys in Ghana, Nepal and Bangladesh.
AB  - BACKGROUND: Current priorities for diarrhoeal disease prevention include use of
      sanitation and safe water. There have been few attempts to quantify the
      importance of animal faeces in drinking-water contamination, despite the presence
      of potentially water-borne zoonotic pathogens in animal faeces. OBJECTIVES: This
      study aimed to quantify the relationship between livestock ownership and point-of
      consumption drinking-water contamination. METHODS: Data from nationally
      representative household surveys in Nepal, Bangladesh, and Ghana, each with
      associated water quality assessments, were used. Multinomial regression adjusting
      for confounders was applied to assess the relationship between livestock
      ownership and the level of drinking-water contamination with E. coli. RESULTS:
      Ownership of five or more large livestock (e.g. cattle) was significantly
      associated with drinking-water contamination in Ghana (RRR=7.9, 95% CI=1.6 to
      38.9 for medium levels of contamination with 1-31cfu/100ml; RRR=5.2, 95% CI=1.1
      24.5 for high levels of contamination with >31cfu/100ml) and Bangladesh (RRR=2.4,
      95% CI=1.3-4.5 for medium levels of contamination; non-significant for high
      levels of contamination). Ownership of eight or more poultry (chickens, guinea
      fowl, ducks or turkeys) was associated with drinking-water contamination in
      Bangladesh (RRR=1.5, 95% CI=1.1-2.0 for medium levels of contamination, non
      significant for high levels of contamination). CONCLUSIONS: These results suggest
      that livestock ownership is a significant risk factor for the contamination of
      drinking-water at the point of consumption. This indicates that addressing human
      sanitation without consideration of faecal contamination from livestock sources
      will not be sufficient to prevent drinking-water contamination.

PMID- 29031737
TI  - The evolution of the genetic code: Impasses and challenges.
AB  - The origin of the genetic code and translation is a "notoriously difficult
      problem". In this survey we present a list of questions that a full theory of the
      genetic code needs to answer. We assess the leading hypotheses according to these
      criteria. The stereochemical, the coding coenzyme handle, the coevolution, the
      four-column theory, the error minimization and the frozen accident hypotheses are
      discussed. The integration of these hypotheses can account for the origin of the
      genetic code. But experiments are badly needed. Thus we suggest a host of
      experiments that could (in)validate some of the models. We focus especially on
      the coding coenzyme handle hypothesis (CCH). The CCH suggests that amino acids
      attached to RNA handles enhanced catalytic activities of ribozymes.
      Alternatively, amino acids without handles or with a handle consisting of a
      single adenine, like in contemporary coenzymes could have been employed. All
      three scenarios can be tested in in vitro compartmentalized systems.

PMID- 29031738
TI  - Concepts, actions, and objects: Functional and neural perspectives.

PMID- 29031739
TI  - Neural correlates of visuospatial bias in patients with left hemisphere stroke: a
      causal functional contribution analysis based on game theory.
AB  - Stroke patients frequently display spatial neglect, an inability to report, or
      respond to, relevant stimuli in the contralesional space. Although this syndrome
      is widely considered to result from the dysfunction of a large-scale attention
      network, the individual contributions of damaged grey and white matter regions to
      neglect are still being disputed. Moreover, while the neuroanatomy of neglect in
      right hemispheric lesions is well studied, the contributions of left hemispheric
      brain regions to visuospatial processing are less well understood. To address
      this question, 128 left hemisphere acute stroke patients were investigated with
      respect to left- and rightward spatial biases measured as severity of deviation
      in the line bisection test and as Center of Cancellation (CoC) in the Bells Test.
      Causal functional contributions and interactions of nine predefined grey and
      white matter regions of interest in visuospatial processing were assessed using
      Multi-perturbation Shapley value Analysis (MSA). MSA, an inference approach based
      on game theory, constitutes a robust and exact multivariate mathematical method
      for inferring functional contributions from multi-lesion patterns. According to
      the analysis of performance in the Bells test, leftward attentional bias
      (contralesional deficit) was associated with contributions of the left superior
      temporal gyrus and rightward attentional bias with contributions of the left
      inferior parietal lobe, whereas the arcuate fascicle was contributed to both
      contra- and ipsilesional bias. Leftward and rightward deviations in the line
      bisection test were related to contributions of the superior longitudinal
      fascicle and the inferior parietal lobe, correspondingly. Thus, Bells test and
      line bisection tests, as well as ipsi- and contralesional attentional biases in
      these tests, have distinct neural correlates. Our findings demonstrate the
      contribution of different grey and white matter structures to contra- and
      ipsilesional spatial biases as revealed by left hemisphere stroke. The results
      provide new insights into the role of the left hemisphere in visuospatial
      processing.

PMID- 29031740
TI  - Eyetracking metrics reveal impaired spatial anticipation in behavioural variant
      frontotemporal dementia.
AB  - Eyetracking technology has had limited application in the dementia field to date,
      with most studies attempting to discriminate syndrome subgroups on the basis of
      basic oculomotor functions rather than higher-order cognitive abilities.
      Eyetracking-based tasks may also offer opportunities to reduce or ameliorate
      problems associated with standard paper-and-pencil cognitive tests such as the
      complexity and linguistic demands of verbal test instructions, and the problems
      of tiredness and attention associated with lengthy tasks that generate few data
      points at a slow rate. In the present paper we adapted the Brixton spatial
      anticipation test to a computerized instruction-less version where oculomotor
      metrics, rather than overt verbal responses, were taken into account as
      indicators of high level cognitive functions. Twelve bvFTD (in whom spatial
      anticipation deficits were expected), six SD patients (in whom deficits were
      predicted to be less frequent) and 38 healthy controls were presented with a 10 *
      7 matrix of white circles. During each trial (N = 24) a black dot moved across
      seven positions on the screen, following 12 different patterns. Participants' eye
      movements were recorded. Frequentist statistical analysis of standard eye
      movement metrics were complemented by a Bayesian machine learning (ML) approach
      in which raw eyetracking time series datasets were examined to explore the
      ability to discriminate diagnostic group performance not only on the overall
      performance but also on individual trials. The original pen and paper Brixton
      test identified a spatial anticipation deficit in 7/12 (58%) of bvFTD and in 2/6
      (33%) of SD patients. The eyetracking frequentist approach reported the deficit
      in 11/12 (92%) of bvFTD and in none (0%) of the SD patients. The machine learning
      approach had the main advantage of identifying significant differences from
      controls in 24/24 individual trials for bvFTD patients and in only 12/24 for SD
      patients. Results indicate that the fine grained rich datasets obtained from
      eyetracking metrics can inform us about high level cognitive functions in
      dementia, such as spatial anticipation. The ML approach can help identify
      conditions where subtle deficits are present and, potentially, contribute to test
      optimisation and the reduction of testing times. The absence of instructions also
      favoured a better distinction between different clinical groups of patients and
      can help provide valuable disease-specific markers.

PMID- 29031741
TI  - Further evidences for sleep instability and impaired spindle-delta dynamics in
      schizophrenia: a whole-night polysomnography study with neuroloop-gain and sleep
      cycle analysis.
AB  - OBJECTIVE: Sleep offers a unique window into the brain dysfunctions in
      schizophrenia. Many past sleep studies have reported abnormalities in both macro
      sleep architecture (like increased awakenings) as well as micro-sleep
      architecture (like spindle deficits) in patients with schizophrenia (PSZ). The
      present study attempts to replicate previous reports of macro- and micro-sleep
      architectural abnormalities in schizophrenia. In addition, the study also
      examined sleep-stage changes and spindle-delta dynamics across sleep-cycles to
      provide further evidence in support of the dysfunctional thalamocortical
      mechanisms causing sleep instability and poor sleep maintenance associated with
      schizophrenia pathophysiology. METHODS: Whole-night polysomnography was carried
      out among 45 PSZ and 39 age- and gender-matched healthy control subjects. Sleep
      stage dynamics were assessed across sleep-cycles using a customized software
      algorithm. Spindle-delta dynamics across sleep-cycles were determined using
      neuroloop-gain analysis. RESULTS: PSZ showed macro-sleep architecture
      abnormalities such as prolonged sleeplessness, increased intermittent-awakenings,
      long sleep-onset latency, reduced non-rapid eye movement (NREM) stage 2 sleep,
      increased stage transitions, and poor sleep efficiency. They also showed reduced
      spindle density (sigma neuroloop-gain) but comparable slow wave density (delta
      neuroloop-gain) throughout the sleep. Sleep-cycle-wise analysis revealed
      transient features of sleep instability due to significantly increased
      intermittent awakenings especially in the first and third sleep-cycles, and
      unstable and recurrent stage transitions in both NREM (first sleep-cycle) and
      rapid eye movement (REM) sleep-periods (second sleep-cycle). Spindle deficits
      were persistent across the first three cycles and were positively correlated with
      sleep disruption during the subsequent REM sleep. CONCLUSIONS: In addition to
      replicating previously reported sleep deficits in PSZ, the current study showed
      subtle deficits in NREM-REM alterations across whole-night polysomnography. These
      results point towards a possible maladaptive interplay between unstable
      thalamocortical networks, resulting in sleep-cycle-specific instability patterns
      associated with schizophrenia pathophysiology.

PMID- 29031742
TI  - A preliminary examination of gut microbiota, sleep, and cognitive flexibility in
      healthy older adults.
AB  - OBJECTIVES: Inadequate sleep increases the risk for age-related cognitive decline
      and recent work suggests a possible role of the gut microbiota in this
      phenomenon. Partial sleep deprivation alters the human gut microbiome, and its
      composition is associated with cognitive flexibility in animal models. Given
      these findings, we examined the possible relationship among the gut microbiome,
      sleep quality, and cognitive flexibility in a sample of healthy older adults.
      METHODS: Thirty-seven participants (age 64.59 +/- 7.54 years) provided a stool
      sample for gut microbial sequencing and completed the Pittsburgh Sleep Quality
      Index and Stroop Color Word Test as part of a larger project. RESULTS: Better
      sleep quality was associated with better Stroop performance and higher
      proportions of the gut microbial phyla Verrucomicrobia and Lentisphaerae. Stroop
      Word and Color-Word performance correlated with higher proportions of
      Verrucomicrobia and Lentisphaerae. Partial correlations suggested that the
      relationship between Lentisphaerae and Stroop Color-Word performance was better
      accounted for by sleep quality; sleep quality remained a significant predictor of
      Color-Word performance, independent of the Lentisphaerae proportion, while the
      relationship between Lentisphaerae and Stroop performance was non-significant.
      Verrucomicrobia and sleep quality were not associated with Stroop Word
      performance independent of one another. CONCLUSIONS: The current findings suggest
      a possible relationship among sleep quality, composition of the gut microbiome,
      and cognitive flexibility in healthy older adults. Prospective and experimental
      studies are needed to confirm these findings and determine whether improving
      microbiome health may buffer against sleep-related cognitive decline in older
      adults.

PMID- 29031744
TI  - College student with actigraphy performed during final examinations.

PMID- 29031743
TI  - Identifying clinically important difference on the Epworth Sleepiness Scale:
      results from a narcolepsy clinical trial of JZP-110.
AB  - BACKGROUND: While scores <=10 on the Epworth Sleepiness Scale (ESS) are within
      the normal range, the reduction in elevated ESS score that is clinically
      meaningful in patients with narcolepsy has not been established. METHODS: This
      post hoc analysis of a clinical trial of patients with narcolepsy evaluated
      correlations between Patient Global Impression of Change (PGI-C) and ESS. Data of
      adult patients with narcolepsy from a double-blind, 12-week placebo-controlled
      study of JZP-110, a wake-promoting agent, were used in this analysis. Descriptive
      statistics and receiver operating characteristic (ROC) analysis compared PGI-C
      (anchor measure) to percent change from baseline in ESS to establish the
      responder criterion from patients taking either placebo or JZP-110 (treatments).
      RESULTS: At week 12, patients (n = 10) who reported being "very much improved" on
      the PGI-C had a mean 76.7% reduction in ESS score, and patients (n = 33) who
      reported being "much improved" on the PGI-C had a mean 49.1% reduction in ESS
      score. ROC analysis showed that patients who improved were almost exclusively
      from JZP-110 treatment group, with an area-under-the-curve of 0.9, and revealed
      that a 25% reduction in ESS (sensitivity, 81.4%; specificity, 80.9%) may be an
      appropriate threshold for defining a meaningful patient response to JZP-110 and
      placebo. CONCLUSIONS: A >=25% reduction in patients' subjective ESS score may be
      useful as a threshold to identify patients with narcolepsy who respond to JZP-110
      treatment.

PMID- 29031745
TI  - Sleep architecture in patients with Juvenile Myoclonic Epilepsy.
AB  - AIM: The aim is to analyze the sleep architecture using polysomnography (PSG) in
      patients with Juvenile Myoclonic Epilepsy (JME): (newly diagnosed and those on
      valproate drug) attending epilepsy clinic at Alexandria University Hospitals.
      METHODS: This study involved 20 patients with JME on valproate (age: 22.40 +/-
      5.80 years; M:F = 6:14), 20 newly diagnosed patients (age: 18.55 +/- 6.0 years;
      M:F = 6:14), and 20 matched healthy controls (age: 22.10 +/- 5.0 years; M:F =
      6:14). Clinical assessment, electroencephalogram (EEG), evaluation with
      comprehensive sleep questionnaire, and PSG were done for all patients. RESULTS:
      PSG showed significant alterations in sleep architecture in the total JME group
      in the form of reduced mean sleep efficiency (p = 0.001*), increased mean Rapid
      eye movement (REM) onset latency (p = 0.046*), decrease mean REM percentage (p =
      0.011*), increased mean wakefulness after sleep onset (p = 0.018*), increase the
      index of total arousal (p = 0.005*), increased mean periodic limb movement index
      (P = 0.001*), and reduced apnea hypopnea index (P = <0.001) in comparison to
      control group. Valproate treated group showed increased sleep efficiency (p =
      0.040*), decreased REM arousal index (P = 0.012), longer stage 3 (P = 0.038), and
      prolonged stage 2 (P = 0.049*) than the newly diagnosed group. CONCLUSIONS: Sleep
      architecture was significantly disturbed in JME, with improvement in sleep
      efficiency in valproate treated patients.

PMID- 29031746
TI  - Relapse insomnia increases greater risk of anxiety and depression: evidence from
      a population-based 4-year cohort study.
AB  - OBJECTIVE: We investigated the longitudinal impacts of insomnia on the subsequent
      developments of anxiety and depression during a four-year follow-up. We further
      categorized individuals with insomnia into different insomnia subgroups to
      examine whether the risk of anxiety and depression varies by subtype. METHODS:
      Participants were identified from National Health Insurance enrollees in Taiwan
      during 2002-2009. The study included 19,273 subjects with insomnia and 38,546
      matched subjects without insomnia. All subjects did not have previous diagnosis
      of insomnia, sleep apnea, anxiety, or depression. RESULTS: Compared with non
      insomniacs, insomniacs had a higher risk of developing anxiety only [adjusted
      hazard ratio (HR) = 8.83, 95% CI = 7.59-10.27], depression only (adjusted HR =
      8.48, 95% CI = 6.92-10.39), and both anxiety and depression (adjusted HR = 17.98,
      95% CI = 12.65-25.56). When breaking down the insomnia subgroups, individuals
      with a relapse of insomnia (adjusted HR = 10.42-26.80) had the highest risk of
      anxiety only, depression only, and both anxiety and depression, followed by
      persistent insomnia (adjusted HR = 9.82-18.98), then remitted insomnia (adjusted
      HR = 4.50-8.27). All three insomnia subgroups had a greater four-year cumulative
      incidence rate than the non-insomnia group for anxiety only, depression only, and
      both anxiety and depression (p < 0.0001). CONCLUSION: Our findings reinforce the
      clinical predictor role of insomnia in the future onset of anxiety or/and
      depression. Awareness of insomnia and treatment of insomnia should be recommended
      at clinics, and patterns of insomnia should be monitored to help treatment and
      control of subsequent psychiatric disorders. Future research with comprehensive
      data collection is needed to identify factors that contribute to different
      insomnia subtypes.

PMID- 29031747
TI  - Sleep phenotypes in infants and toddlers with neurogenetic syndromes.
AB  - BACKGROUND: Although sleep problems are well characterized in preschool- and
      school-age children with neurogenetic syndromes, little is known regarding the
      early emergence of these problems in infancy and toddlerhood. To inform syndrome
      specific profiles and targets for intervention, we compared parent-reported sleep
      problems in infants and toddlers with Angelman syndrome (AS), Williams syndrome
      (WS), and Prader-Willi syndrome (PWS) with patterns observed among same-aged
      typically developing (TD) controls. METHODS: Mothers of 80 children (18 AS, 19
      WS, 19 PWS, and 24 TD) completed the Brief Infant Sleep Questionnaire. Primary
      dependent variables included (1) sleep onset latency, (2) total sleep duration,
      (3) daytime and nighttime sleep duration, and (4) sleep problem severity, as
      measured by both maternal impression and National Sleep Foundation guidelines.
      RESULTS: Sleep problems are relatively common in children with neurogenetic
      syndromes, with 41% of mothers reporting problematic sleep and 29% of children
      exhibiting abnormal sleep durations as per national guidelines. Across genetic
      subgroups, problems are most severe in children with AS and WS, particularly in
      relation to nighttime sleep duration. Although atypical sleep is
      characteristically reported in each syndrome later in development, infants and
      toddlers with PWS exhibited largely typical patterns, potentially indicating
      delayed onset of sleep problems in concordance with other medical features of
      PWS. CONCLUSIONS: Our findings suggest that sleep problems in neurogenetic
      syndromes emerge as early as infancy and toddlerhood, with variable profiles
      across genetic subgroups. This work underscores the importance of early sleep
      screenings as part of routine medical care of neurosyndromic populations and the
      need for targeted, syndrome-sensitive treatment.

PMID- 29031749
TI  - Vagal nerve stimulator induced chin electromyography artifact.

PMID- 29031748
TI  - Association of sleep duration and incidence of diabetes modified by tea
      consumption: a report from the Shanghai men's health study.
AB  - OBJECTIVES: To evaluate the association between sleep duration and the incidence
      of diabetes stratified by sleep-related factors among Chinese men. METHODS: This
      study included 34,825 men who provided information on sleep-related questions in
      the Shanghai Men's Health Study, a population-based cohort study conducted in
      Shanghai, China from 2002 to 2011. Participants were excluded who had a history
      of diabetes or who were diagnosed with diabetes within 2 years of recruitment.
      Cox regression was employed to evaluate the influence of sleep duration and its
      interaction with sleep-related factors on diabetes risk. RESULTS: A total of 1521
      incident cases were documented during a median of 5.6 follow-up years. Adjusted
      hazard ratios and 95% confidence intervals were 1.0 (0.9-1.1) and 1.2 (1.0-1.3)
      for men who slept <7 and >=8 h per day, respectively, compared with those who
      slept 7 h per day (ptrend = 0.01). Stratified analyses revealed that the
      association between sleep duration and risk of diabetes was only statistically
      significant among current smokers and regular drinkers, never tea drinkers, men
      with a high body mass index, hypertension or comorbidity, and men who did not
      work nightshift or who snored. A statistically significant interaction between
      tea drinking and sleep duration was observed (pinteraction = 0.01). The above
      association patterns remained when daytime nappers were excluded from the
      analyses. CONCLUSIONS: The data suggested that longer sleep duration,
      particularly among individuals already exhibiting factors linked to poor quality
      of sleep, was associated with diabetes. The association between sleep duration
      and diabetes may be modified by tea drinking, especially in older men or men with
      more sleep-related factors.

PMID- 29031750
TI  - The urge to move and breathe - the impact of obstructive sleep apnea syndrome
      treatment in patients with previously diagnosed, clinically significant restless
      legs syndrome.
AB  - OBJECTIVE: The association between restless legs syndrome (RLS) and obstructive
      sleep apnea syndrome (OSAS) has seldom been reported. There is one study
      reporting improvement of RLS symptoms severity in patients naive of treatment
      after initiation of continuous positive airway pressure (CPAP) for OSAS. The aim
      of this study was to evaluate the impact of the OSAS treatment in patients with
      previously diagnosed, clinically significant RLS in a usual clinical setting.
      METHODS: This was a retrospective study of RLS patients from a sleep clinic with
      a concomitant or subsequent diagnosis of OSAS. All patients who started treatment
      for OSAS and had a follow-up of >=3 months were selected. Exclusion criteria
      included noncompliance, absence of sufficient information on clinical records,
      and RLS improvement following treatment of secondary causes. The primary outcome
      variable was clinical status of RLS symptoms following OSA treatment. Other
      variables included demographics, RLS treatment and outcome, OSA diagnosis,
      treatment, compliance, outcome, and PSG characteristics. RESULTS: From a database
      of 97 RLS patients, 56 patients had both OSA and RLS. Of these patients, 28 met
      the criteria for the study. In all, 17 patients (60.9%) were female, with a mean
      age 60 years. A total of 16 patients (57.1%) were diagnosed with idiopathic RLS.
      OSAS was diagnosed, on average, 21 months after the RLS diagnosis. A total of 19
      (70.4%) patients were overweight or obese, 26 (92.9%) reported snoring, and 10
      (35.7%) witnessed apneas. A total of 16 patients (57.1%) had excessive daytime
      sleepiness and 23 (84.1%) had insomnia. The mean apnea-hypopnea index was 19.
      Patients were mostly treated with dopamine agonists (19 patients, 67.9%) for the
      RLS, and nine patients were treated with more than two drugs for RLS. A total of
      20 patients (71.4%) had improvement of symptoms of RLS after therapy for OSAS, of
      whom nine stopped drug therapy and eight reduced the dose. CONCLUSIONS: In
      patients with clinically significant RLS, treatment of concomitant OSAS
      significantly improved RLS symptoms, enabling drug therapy reduction in more than
      half of the patients. These data reinforce the need to actively diagnose OSAS in
      RLS patients.

PMID- 29031751
TI  - Phasic activity and the importance of irregular breathing.

PMID- 29031752
TI  - Sleep and slow-wave activity in depressed adolescent boys: a preliminary study.
AB  - OBJECTIVE: Adolescence is a vulnerable period of life that is characterized by
      increasing incidence of depression. Sleep disturbance is one of the diagnostic
      symptoms of depressive disorder. Adolescence is also characterized by dramatic
      maturational changes in sleep and its regulation. The goal of this study was to
      assess sleep macroarchitecture and slow-wave activity (SWA) in depressed
      adolescent boys. METHODS: Eight non-medicated adolescent boys meeting the
      Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for
      depressive disorder and 10 age-matched healthy controls (average age 16.0 years)
      underwent polysomnography in their home environment for two consecutive nights.
      Sleep macroarchitecture, SWA, and SWA dissipation were assessed in all subjects.
      RESULTS: Depressed boys showed a flattened pattern of SWA dissipation through the
      night. SWA power was lower during the first non-rapid eye movement (NREM) episode
      in the frontal derivation and higher during the third NREM episode in the central
      derivation in the group of depressed boys as compared to healthy boys. The SWA
      dissipation pattern correlated with the severity of depressive symptoms, and the
      correlation was strongest in the frontal derivation. In addition, total sleep
      time was shorter in patients as compared to the control group, but no other
      differences were found in the macroarchitecture of sleep. CONCLUSION: Depression
      in adolescent boys is characterized by more evenly distributed SWA through the
      night as compared to healthy subjects, and we showed for the first time that this
      pattern of SWA distribution is associated with severity of depressive symptoms.
      These findings suggest that homeostatic regulation of sleep may be impaired in
      adolescent depression.

PMID- 29031753
TI  - The short and long of adolescent sleep: the unique impact of day length.
AB  - STUDY OBJECTIVES: Variation in day length is proposed to impact sleep, yet it is
      unknown whether this is above the influence of behavioural factors. Day length,
      sleep hygiene, and parent-set bedtime were simultaneously explored, to
      investigate the relative importance of each on adolescents' sleep. METHODS: An
      online survey was distributed in four countries at varying latitudes/longitudes
      (Australia, The Netherlands, Canada, Norway). RESULTS: Overall, 711 (242 male;
      age M = 15.7 +/- 1.6, range = 12-19 yrs) adolescents contributed data.
      Hierarchical regression analyses showed good sleep hygiene was associated with
      earlier bedtime, shorter sleep latency, and longer sleep (beta = -0.34; -0.30;
      0.32, p < 0.05, respectively). Shorter day length predicted later bedtime (beta =
      0.11, p = 0.009), decreased sleep latency (beta = -0.21, p < 0.001), and total
      sleep (beta = -0.14, p = 0.001). Longer day length predicted earlier bedtimes
      (beta = -0.11, p = 0.004), and longer sleep (beta = 0.10, p = 0.011).
      CONCLUSIONS: Sleep hygiene had the most clinical relevance for improving sleep,
      thus should be considered when implementing adolescent sleep interventions,
      particularly as small negative effects of shorter day length may be minimised
      through sleep hygiene techniques.

PMID- 29031754
TI  - Predictors of insomnia onset in adolescents in Japan.
AB  - OBJECTIVE: The objective of this study was to clarify the incidence rate and
      predictive factors of insomnia in Japanese junior and senior high school
      students. METHODS: We conducted a baseline survey on first year junior and senior
      high school students (seventh and 10th graders) throughout the nation. A follow
      up survey was then conducted two years later. For both surveys, we used self
      administered questionnaires inquiring about sleep, mental health status,
      lifestyle, participation in club activities, and study hours. RESULTS: A total of
      3473 students (776 junior high and 2697 senior high) were suitable for analysis.
      During the two years leading to the follow-up study, the incidence rate of newly
      developed insomnia was 7.8% among junior high and 9.2% among senior high school
      students. Multiple logistic regression analyses revealed that factors associated
      with new insomnia onset were 'sleep paralysis experience' and 'poor mental health
      status' in junior high school students, and 'being woken by a nightmare', 'poor
      mental health status', '>=2 h of extracurricular learning per day' and 'mobile
      phone use for >=2 h per day' in senior high school students. CONCLUSIONS: In
      junior and senior high school students, parasomnias such as nightmares and sleep
      paralysis, and mental health status can be predictors of insomnia onset. For
      senior high school students, longer use of mobile phones can be a predictor of
      insomnia onset. The present findings suggest that sleep health must be promoted
      among junior and senior high school students in the future.

PMID- 29031755
TI  - Allocating provider resources to diagnose and treat restless legs syndrome: a
      cost-utility analysis.
AB  - OBJECTIVES: Restless legs syndrome (RLS) is a neurological disorder that is
      frequently misdiagnosed, resulting in delays in proper treatment. The objective
      of this study was to analyze the cost-utility of training primary care providers
      (PCP) in early and accurate diagnosis of RLS. METHODS: We used a Markov model to
      compare two strategies: one where PCPs received training to diagnose RLS
      (informed care) and one where PCPs did not receive training (standard care). This
      analysis was conducted from the US societal and health sector perspectives over
      one-year, five-year, and lifetime (50-year) horizons. Costs were adjusted to 2016
      USD, utilities measured as quality-adjusted life-years (QALYs), and both measures
      were discounted annually at 3%. Cost, utilities, and probabilities for the model
      were obtained through a comprehensive review of literature. An incremental cost
      effectiveness ratio (ICER) was calculated to interpret our findings at a
      willingness-to-pay threshold of $100,000/QALY. Univariate and multivariate
      analyses were conducted to test model uncertainty, in addition to calculating the
      expected value of perfect information. RESULTS: Providing training to PCPs to
      correctly diagnose RLS was cost-effective since it cost $2021 more and gained
      0.44 QALYs per patient over the course of a lifetime, resulting in an ICER of
      $4593/QALY. The model was sensitive to the utility for treated and untreated RLS.
      The probabilistic sensitivity analysis revealed that at $100,000/QALY, informed
      care had a 65.5% probability of being cost-effective. CONCLUSION: A program to
      train PCPs to better diagnose RLS appears to be a cost-effective strategy for
      improving outcomes for RLS patients.

PMID- 29031756
TI  - Obstructive sleep apnea in pregnancy is associated with adverse maternal
      outcomes: a national cohort.
AB  - OBJECTIVE: Pregnancy and the obesity epidemic impacting women of reproductive age
      appear to predispose women to obstructive sleep apnea (OSA) in pregnancy. The aim
      of this study is to examine the association between OSA and adverse maternal
      outcomes in a national cohort. METHODS: The National Perinatal Information Center
      in the US was used to identify women with a delivery discharge diagnosis of OSA
      from 2010 to 2014. We used the International Classification of Diseases, ninth
      Revision to classify OSA diagnosis and maternal outcomes. MEASUREMENTS: The
      sample consisted of 1,577,632 gravidas with a rate of OSA of 0.12% (N = 1963).
      There was a significant association between OSA and preeclampsia (adjusted odds
      ratio (aOR) 2.22, 95% confidence interval (CI) 1.94-2.54), eclampsia (aOR 2.95,
      1.08-8.02), and gestational diabetes (aOR 1.51, 1.34-1.72) after adjusting for a
      comprehensive list of covariates which includes maternal obesity. OSA status was
      also associated with a 2.5-3.5-fold increase in risk of severe complications such
      as cardiomyopathy, congestive heart failure, and hysterectomy. Length of hospital
      stay was significantly longer (5.1 + 5.6 vs 3.0 + 3.0 days, p < 0.001) and odds
      of an admission to an intensive care unit higher (aOR 2.74, 2.36-3.18) in women
      with OSA. CONCLUSIONS: Compared to pregnant women without OSA, pregnant women
      with OSA have a significantly higher risk of pregnancy-specific complications
      such as gestational hypertensive conditions and gestational diabetes, and rare
      medical and surgical complications such as cardiomyopathy, pulmonary edema,
      congestive heart failure, and hysterectomy. OSA diagnosis was also associated
      with a longer hospital stay and significantly increased odds for admission to the
      intensive care unit.

PMID- 29031757
TI  - What predicts inattention in adolescents? An experience-sampling study comparing
      chronotype, subjective, and objective sleep parameters.
AB  - OBJECTIVE: Many adolescents sleep insufficiently, which may negatively affect
      their functioning during the day. To improve sleep interventions, we need a
      better understanding of the specific sleep-related parameters that predict poor
      functioning. We investigated to which extent subjective and objective parameters
      of sleep in the preceding night (state parameters) and the trait variable
      chronotype predict daytime inattention as an indicator of poor functioning.
      METHODS: We conducted an experience-sampling study over one week with 61
      adolescents (30 girls, 31 boys; mean age = 15.5 years, standard deviation = 1.1
      years). Participants rated their inattention two times each day (morning,
      afternoon) on a smartphone. Subjective sleep parameters (feeling rested, positive
      affect upon awakening) were assessed each morning on the smartphone. Objective
      sleep parameters (total sleep time, sleep efficiency, wake after sleep onset)
      were assessed with a permanently worn actigraph. Chronotype was assessed with a
      self-rated questionnaire at baseline. We tested the effect of subjective and
      objective state parameters of sleep on daytime inattention, using multilevel
      multiple regressions. Then, we tested whether the putative effect of the trait
      parameter chronotype on inattention is mediated through state sleep parameters,
      again using multilevel regressions. RESULTS: We found that short sleep time, but
      no other state sleep parameter, predicted inattention to a small effect. As
      expected, the trait parameter chronotype also predicted inattention: morningness
      was associated with less inattention. However, this association was not mediated
      by state sleep parameters. CONCLUSIONS: Our results indicate that short sleep
      time causes inattention in adolescents. Extended sleep time might thus alleviate
      inattention to some extent. However, it cannot alleviate the effect of being an
      'owl'.

PMID- 29031758
TI  - The association of mothers' and fathers' insomnia symptoms with school-aged
      children's sleep assessed by parent report and in-home sleep
      electroencephalography.
AB  - OBJECTIVE: Sleep plays an essential role for children's well-being. Because
      children's sleep is associated with parental sleep patterns, it must be
      considered in the family context. As a first aim of the present study, we test
      whether parental insomnia symptoms are related to children's in-home sleep
      electroencephalography (EEG). Second, we examine the association between parental
      insomnia symptoms and maternal and paternal perception of children's sleep using
      actor-partner interdependence models. METHODS: A total of 191 healthy children
      enrolled in public school and aged 7-12 years took part in the study. Ninety-six
      were formerly very preterm born children. Children underwent in-home sleep-EEG,
      and parents reported children's sleep-related behavior by using the German
      version of the Children's Sleep Habits Questionnaire. Further, parents completed
      the Insomnia Severity Index to report their own insomnia symptoms. RESULTS:
      Maternal but not paternal insomnia symptoms were related to less children's EEG
      derived total sleep time, more stage 2 sleep, less slow wave sleep, later sleep
      onset time, and later awakening time. Mothers' and fathers' own insomnia symptoms
      were related to their reports of children's bedtime resistance, sleep duration,
      sleep anxiety, night wakings, and/or daytime sleepiness. Moreover, maternal
      insomnia symptoms were associated with paternal reports of children's bedtime
      resistance, sleep anxiety, and sleep-disordered breathing. The associations
      between parental insomnia symptoms and parents' perception of children's sleep
      could not be explained by children's objectively measured sleep. CONCLUSIONS:
      Mothers' insomnia symptoms and children's objective sleep patterns are
      associated. Moreover, the parents' own insomnia symptoms might bias their
      perception of children's sleep-related behavior problems.

PMID- 29031759
TI  - Periodic neck myoclonus during sleep.

PMID- 29031760
TI  - Impact of diagnosing and treating obstructive sleep apnea on healthcare
      utilization.
AB  - PURPOSE: Obstructive sleep apnea (OSA) contributes to an increased risk for
      multiple co-morbidities and decreased quality of life. As a result, OSA patients
      may have higher usage of healthcare resources which can be mitigated with
      effective treatment. This study evaluates changes in healthcare utilization (HCU)
      following the initiation of therapy for OSA. METHODS: We conducted a
      retrospective study of newly diagnosed OSA patients. To assess total HCU, we
      incorporated the sum total of outpatient clinic encounters, laboratory tests, and
      medication prescriptions into a composite HCU score. Healthcare utilization for
      twelve months prior to positive airway pressure (PAP) was compared with twelve
      months after initiation of therapy. Reductions in HCU were correlated with PAP
      adherence. RESULTS: 650 consecutive patients were included. Mean age, gender,
      BMI, AHI, and ESS were 47.2 +/- 8.8 years, 77.2% (men), 30.7 +/- 4.9 kg/m2, 37.1
      +/- 30.3, and 13.1 +/- 5.1, respectively. Prior to PAP, mean outpatient visits,
      laboratory studies, medication prescriptions, and HCU composite score were 11.6
      +/- 10.4, 13.7 +/- 11.0, 4.7 +/- 3.2, and 29.7 +/- 18.6, respectively. Following
      initiation of treatment, a 32.8% reduction in non-sleep outpatient visits was
      identified (p = 0.01) and a 16.4% decrease in laboratory studies (p = 0.02) was
      observed. There was a 19.9% reduction (p = 0.002) in HCU composite score. Those
      who were adherent with PAP had a 25.7% reduction in HCU composite score versus a
      4.9% increase in those who discontinued PAP therapy (p < 0.001). CONCLUSIONS:
      Diagnosing OSA and initiating PAP therapy resulted in a significant decrease in
      healthcare resource utilization. This reduction was greatest among those with
      higher baseline healthcare usage and those most adherent with therapy.

PMID- 29031761
TI  - Reduced P300 amplitude during a visuospatial attention task in idiopathic rapid
      eye movement sleep behavior disorder.
AB  - OBJECTIVES: Idiopathic rapid eye movement sleep behavior disorder (IRBD) patients
      are prone to cognitive deficits, which include attention, executive, and
      visuospatial dysfunctions. Even patients with normal cognition may exhibit
      subclinical electrophysiological dysfunction. This study aimed to evaluate
      visuospatial attention processing in IRBD patients with normal cognition and to
      compare their findings with those of age- and sex-matched healthy controls.
      METHODS: We recorded event-related potentials (ERPs) and performance measures
      during a variant of the Posner task in 14 IRBD patients and 14 control subjects.
      Behavioral data and the mean P300 amplitude were compared between groups.
      RESULTS: No group difference was found for reaction time or accuracy, but a
      significant group effect was observed for the P300 amplitude. IRBD patients had
      reduced P300 amplitude (MUV) than controls in both valid (IRBD: 0.53 +/- 1.05 vs
      Controls: 1.61 +/- 0.95; p = 0.008) and invalid (IRBD: 0.74 +/- 0.99 vs Controls:
      1.73 +/- 0.86; p = 0.009) conditions. The P300 amplitude was correlated with
      Montreal cognitive assessment (MOCA) scores (r = 0.424, p = 0.024). CONCLUSION:
      Reduced P300 amplitude during the Posner task provides electrophysiological
      evidence for subclinical visuospatial attention deficits in cognitively normal
      IRBD patients. The results of this study imply that cortical dysfunction is
      already present in patients with IRBD in their early disease stage.

PMID- 29031762
TI  - Sleep and cognitive performance: cross-sectional associations in the UK Biobank.
AB  - OBJECTIVE: The relationship between insomnia symptoms and cognitive performance
      is unclear, particularly at the population level. We conducted the largest
      examination of this association to date through analysis of the UK Biobank, a
      large population-based sample of adults aged 40-69 years. We also sought to
      determine associations between cognitive performance and self-reported
      chronotype, sleep medication use and sleep duration. METHODS: This cross
      sectional, population-based study involved 477,529 participants, comprising
      133,314 patients with frequent insomnia symptoms (age: 57.4 +/- 7.7 years; 62.1%
      female) and 344,215 controls without insomnia symptoms (age: 56.1 +/- 8.2 years;
      52.0% female). Cognitive performance was assessed by a touchscreen test battery
      probing reasoning, basic reaction time, numeric memory, visual memory, and
      prospective memory. Adjusted models included relevant demographic, clinical, and
      sleep variables. RESULTS: Frequent insomnia symptoms were associated with
      cognitive impairment in unadjusted models; however, these effects were reversed
      after full adjustment, leaving those with frequent insomnia symptoms showing
      statistically better cognitive performance over those without. Relative to
      intermediate chronotype, evening chronotype was associated with superior task
      performance, while morning chronotype was associated with the poorest
      performance. Sleep medication use and both long (>9 h) and short (<7 h) sleep
      durations were associated with impaired performance. CONCLUSIONS: Our results
      suggest that after adjustment for potential confounding variables, frequent
      insomnia symptoms may be associated with a small statistical advantage, which is
      unlikely to be clinically meaningful, on simple neurocognitive tasks. Further
      work is required to examine the mechanistic underpinnings of an apparent evening
      chronotype advantage in cognitive performance and the impairment associated with
      morning chronotype, sleep medication use, and sleep duration extremes.

PMID- 29031763
TI  - Correlation between the Epworth Sleepiness Scale and the Maintenance of
      Wakefulness Test in patients with narcolepsy participating in two clinical trials
      of sodium oxybate.
AB  - BACKGROUND: In evaluating pathologic sleepiness, the Epworth Sleepiness Scale
      (ESS) assesses subjective sleep propensity; the Maintenance of Wakefulness Test
      (MWT) is an objective measure of the ability to stay awake. This analysis
      evaluated the strength of the correlation between ESS and MWT with regard to
      absolute values in scores. METHODS: Data were analyzed separately from the intent
      to-treat populations of two eight-week clinical trials of sodium oxybate for the
      treatment of narcolepsy, SXB-15 and SXB-22. For all treatment groups,
      correlations between ESS and MWT were evaluated at baseline, week four, and week
      eight using the Pearson product-moment correlation coefficient. RESULTS: Overall,
      correlations across all treatment groups in each study described an inverse
      relationship, reflecting the scoring of each measure (ie, whereas higher ESS
      scores indicate greater sleepiness, higher MWT scores indicate a greater ability
      to remain awake). Significant correlations of low-to-moderate strength were
      observed at all time points in both studies. In SXB-15, correlation coefficients
      were -0.272, -0.365, and -0.343 at baseline (n = 221), week four (n = 212), and
      week eight (n = 205), respectively, with all P < 0.0001. Similarly, in SXB-22,
      correlation coefficients were -0.302 (n = 216), -0.418 (n = 211), and -0.432 (n =
      196) at the three time points, respectively, also with all P < 0.0001.
      CONCLUSION: Although all correlations showed statistical significance, they were
      of low-to-moderate strength. These results indicate that ESS and MWT measure
      features of pathologic sleepiness that may be distinct, but partially
      overlapping. These data corroborate those of other studies, suggesting that
      physiologic mechanisms that regulate alertness and sleep propensity may function
      somewhat independently.

PMID- 29031764
TI  - Combined resting state functional magnetic resonance imaging and diffusion tensor
      imaging study in patients with idiopathic restless legs syndrome.
AB  - OBJECTIVE: Restless legs syndrome (RLS) is a common neurological disorder
      characterized by an urge to move the legs along with paraesthesia deep within
      them. In this study, we aimed to use diffusion tensor imaging (DTI) and regional
      homogeneity (ReHo) to investigate the changes in regional spontaneous brain
      activity change for RLS patients against age- and gender-matched normal control
      (NC) subjects. METHODS: A total of 35 RLS patients and 27 age- and gender-matched
      NC subjects were recruited for group comparison research that used DTI and ReHo
      techniques. DTI was analysed by FSL and tract-based spatial statistics (TBSS)
      software to measure the values of fractional anisotropy (FA) or mean diffusivity
      (MD) in brain regions. Statistical Parametric Mapping 8 (SPM8) was used for data
      preprocessing and Data Processing Assistant for Resting-State fMRI (DPARSF)
      toolbox was used for ReHo calculation. For multiple comparison correction, the
      AlphaSim program implemented in AFNI was used to control the false-positive rate
      (corrected p < 0.05). RESULTS: There was no significant difference between the
      iRLS and NC groups in age or gender. In the one-sample t-test, both the NC and
      RSL groups showed increased ReHo in the bilateral posterior cingulate/precuneus
      cortex compared to the groups' global means, indicating that the default mode
      network was at rest. The RLS group showed a smaller cluster size than the NC
      group. In the two-sample t-test, the RLS group showed increased ReHo in the
      bilateral middle frontal gyrus, anterior cingulate cortex, caudate nucleus,
      insula, thalamus, putamen and left posterior cingulate cortex compared to the NC
      group. The statistical analysis of DTI images did not show any difference between
      the two groups. TBSS group comparison did not reveal any difference in FA or mean
      diffusivity (MD) of any brain region. CONCLUSION: RLS patients showed that
      greater ReHo within the striatum, thalamus and the limbic system, which implies
      that the emotional processing, motion control and cognition in the cortico
      striatal-thalamic-cortical (CSTC) loop may be the site of dysfunction in RLS
      patients. This finding may provide imaging evidence to explore the
      pathophysiology of RLS. On the other hand, we did not see any change in the
      microstructure in the DTI analysis for RLS patients when compared to the NC
      group, which suggests a metabolic impairment.

PMID- 29031766
TI  - Disulfide bond formation protects Arabidopsis thaliana glutathione transferase
      tau 23 from oxidative damage.
AB  - BACKGROUND: Glutathione transferases play an important role as detoxifying
      enzymes. In A. thaliana, elevated levels of reactive oxygen species (ROS),
      provoked during biotic and abiotic stress, influence the activity of GSTU23. The
      aim of this study is to determine the impact of oxidative stress on the function
      and structure of GSTU23. METHODS: The impact of oxidation on the function of
      GSTU23 was studied using a glutathione transferase biochemical assay and mass
      spectrometry. With kinetics, circular dichroism and thermodynamics, we compared
      reduced with oxidized GSTU23. X-ray crystal structures of GSTU23 visualize the
      impact of oxidation on methionines and cysteines. RESULTS: In the presence of
      100MUM H2O2, oxidation of the methionine side-chain to a sulfoxide is the
      prominent post-translational modification, which can be reduced by C. diphtheriae
      MsrA and MsrB. However, increasing the level to 200MUM H2O2 results in a
      reversible intramolecular disulfide between Cys65-Cys110, which is substrate for
      glutaredoxin. Under these oxidizing conditions, GSTU23 undergoes a structural
      change and forms a more favourable enzyme-substrate complex to overcome kcat
      decrease. CONCLUSIONS AND SIGNIFICANCE: At lower H2O2 levels (100MUM), GSTU23
      forms methionine sulfoxides. Specifically, oxidation of Met14, located near the
      catalytic Ser13, could interfere with both GSH binding and catalytic activation.
      At higher H2O2 levels (200MUM), the Cys65-Cys110 disulfide bond protects other
      cysteines and also methionines from overoxidation. This study shows the impact of
      oxidative stress on GSTU23 regulated by methionine sulfoxide reductases and
      glutaredoxin, and the mechanisms involved in maintaining its catalytic
      functionality under oxidizing conditions.

PMID- 29031767
TI  - Cycling, and Male Sexual and Urinary Function: Results from a Large,
      Multinational, Cross-Sectional Study.
AB  - PURPOSE: We explored the relation of cycling to urinary and sexual function in a
      large multinational sample of men. MATERIALS AND METHODS: Cyclists were recruited
      to complete a survey through Facebook(r) advertisements and outreach to sporting
      clubs. Swimmers and runners were recruited as a comparison group. Cyclists were
      categorized into low and high intensity cyclists. Participants were queried using
      validated questionnaires, including SHIM (Sexual Health Inventory for Men), I-PSS
      (International Prostate Symptom Score) and NIH-CPSI (National Institutes of
      Health Chronic Prostatitis Symptom Index), in addition to questions about urinary
      tract infections, urethral stricture, genital numbness and saddle sores. RESULTS:
      Of 5,488 complete survey responses 3,932 (72%) were included in our analysis. On
      multivariate analysis swimmers/runners had a lower mean SHIM score than low and
      high intensity cyclists (19.5 vs 19.9 and 20.7, p = 0.02 and <0.001,
      respectively). No significant differences were found in I-PSS or NIH-CPSI scores,
      or urinary tract infection history. Cyclists had statistically higher odds of
      urethral stricture compared to swimmers/runners (OR 2.5, p = 0.042). Standing
      more than 20% of the time while cycling significantly reduced the odds of genital
      numbness (OR 0.4, p = 0.006). Adjusting the handlebar higher or even with the
      saddle had lower odds of genital numbness and saddle sores (OR 0.8, p = 0.005 and
      0.6, p <0.001, respectively). CONCLUSIONS: Cyclists had no worse sexual or
      urinary functions than swimmers or runners but cyclists were more prone to
      urethral stricture. Increased time standing while cycling and a higher handlebar
      height were associated with lower odds of genital sores and numbness.

PMID- 29031765
TI  - An increased autophagic flux contributes to the anti-inflammatory potential of
      urolithin A in macrophages.
AB  - BACKGROUND: An extract of Phyllanthus muellerianus and its constituent geraniin
      have been reported to exert anti-inflammatory activity in vivo. However, orally
      consumed geraniin, an ellagitannin, shows low bioavailability and undergoes
      metabolization to urolithins by gut microbiota. This study aimed at comparing
      geraniin and urolithin A with respect to inhibition of M1 (LPS) polarization of
      murine J774.1 macrophages and shedding more light on possible underlying
      mechanisms. METHODS: Photometric, fluorimetric as well as luminescence-based
      assays monitored production of reactive oxygen species (ROS) and nitric oxide
      (NO), cell viability or reporter gene expression. Western blot analyses and
      confocal microscopy showed abundance and localization of target proteins,
      respectively. RESULTS: Urolithin A is a stronger inhibitor of M1 (LPS) macrophage
      polarization (production of NO, ROS and pro-inflammatory proteins) than geraniin.
      Urolithin A leads to an elevated autophagic flux in macrophages. Inhibition of
      autophagy in M1 (LPS) macrophages overcomes the suppressed nuclear translocation
      of p65 (NF-kB; nuclear factor kB), the reduced expression of pro-inflammatory
      genes as well as the diminished NO production brought about by urolithin A. The
      increased autophagic flux is furthermore associated with impaired Akt/mTOR
      (mammalian target of rapamycin) signaling in urolithin A-treated macrophages.
      CONCLUSIONS AND GENERAL SIGNIFICANCE: Intestinal metabolization may boost the
      potential health benefit of widely consumed dietary ellagitannins, as suggested
      by side by side comparison of geraniin and urolithin A in M1(LPS) macrophages.
      Increased activity of the autophagic cellular recycling machinery aids the anti
      inflammatory bioactivity of urolithin A.

PMID- 29031768
TI  - A Double-Blind, Randomized Trial on the Efficacy and Safety of Hyperbaric
      Oxygenation Therapy in the Preservation of Erectile Function after Radical
      Prostatectomy.
AB  - PURPOSE: We evaluated the efficacy and safety of hyperbaric oxygenation therapy
      to preserve erectile function as part of penile rehabilitation after robot
      assisted bilateral nerve sparing radical prostatectomy for prostate cancer.
      MATERIALS AND METHODS: We performed a prospective, randomized, double-blind study
      from January 2009 to April 2013. Men 40 to 65 years old who underwent robot
      assisted bilateral nerve sparing radical prostatectomy were randomized 1:1 to the
      control or the treatment group. Participants were exposed to air as the control
      or to 100% oxygen as the treatment in hyperbaric conditions. The primary outcome
      was erectile function at 18 months as measured by IIEF (International Index of
      Erectile Function). Secondary outcomes were 12-month urinary symptoms, and 18
      month sexual, urinary, bowel and hormonal related symptoms as measured by EPIC-26
      (Expanded Prostate Index Composite-26). Adverse events and long-term cancer
      outcomes were monitored. Primary and secondary outcomes in the 2 groups were
      compared by the independent group t-test, the Wilcoxon rank sum test and the chi
      square test of proportion. RESULTS: A total of 109 potent men were randomized to
      hyperbaric oxygenation therapy or the control group. A total of 43 men in the air
      group and 40 in the hyperbaric oxygenation therapy group completed the 18-month
      followup. No statistically significant differences were observed between the 2
      groups on any outcome measure. CONCLUSIONS: This study revealed no difference in
      erectile recovery in men treated with hyperbaric oxygenation therapy vs placebo.
      Larger studies involving more diverse comorbidities and different hyperbaric
      oxygenation therapy regimens are needed to better evaluate the usefulness of
      hyperbaric oxygenation therapy for penile rehabilitation after radical
      prostatectomy.

PMID- 29031769
TI  - Intratrigonal OnabotulinumtoxinA Improves Bladder Symptoms and Quality of Life in
      Patients with Bladder Pain Syndrome/Interstitial Cystitis: A Pilot, Single
      Center, Randomized, Double-Blind, Placebo Controlled Trial.
AB  - PURPOSE: We compared the efficacy and safety of trigonal injections of
      onabotulinumtoxinA and saline in patients with bladder pain syndrome/interstitial
      cystitis. MATERIALS AND METHODS: This phase II study enrolled women who had had
      bladder pain syndrome/interstitial cystitis for more than 6 months and pain for 4
      months or longer on a visual analogue scale of 0 to 10, which were refractory to
      common treatment. OnabotulinumtoxinA 100 U in 10 or saline as placebo in 9 was
      administered as 10 trigonal injections of 1 ml. The primary study end point was
      the change from baseline pain intensity reported at week 12. Additional end
      points included O'Leary-Sant scores, micturition frequency, quality of life at
      week 4, 8 and 12, and the treatment benefit scale at week 12. Safety assessments
      included urinary tract infection, post-void residual urine and the initiation of
      clean intermittent catheterization. RESULTS: At week 12 onabotulinumtoxinA had
      significantly reduced pain compared with saline (mean +/- SD -3.8 +/- 2.5 vs -1.6
      +/- 2.1, p <0.05). The proportion of patients who achieved a 50% or greater
      reduction in the pain visual analog scale was 60% for onabotulinumtoxinA vs 22%
      for placebo. OnabotulinumtoxinA significantly improved O'Leary-Sant scores and
      quality of life over placebo at weeks 4, 8 and 12. Important numerical reductions
      in voiding frequency were also observed with the toxin. OnabotulinumtoxinA was
      well tolerated. Urinary tract infections developed in 3 patients who received
      onabotulinumtoxinA vs 2 who received saline. Mean post-void residual urine at
      week 12 was 5 +/- 13 ml for onabotulinumtoxinA vs 0 ml with saline. This study
      had the limitations inherent to a single center trial with a small number of
      patients enrolled. CONCLUSIONS: OnabotulinumtoxinA 100 U caused significant and
      clinically relevant improvements in bladder pain and quality of life in patients
      with bladder pain syndrome/interstitial cystitis refractory to common therapy. It
      was also well tolerated.

PMID- 29031770
TI  - Effects of three major amino acids found in Japanese broth on glucose metabolism
      and gastric emptying.
AB  - OBJECTIVES: To our knowledge, the effect of the broth of dried kelp and dried
      bonito, dashi, on glucose metabolism and digestion has rarely been studied. Based
      on the component analysis of three actual broths served in traditional
      restaurants, a chemically synthesized broth with three free amino acids
      (histidine, glutamate, aspartate) and salt was prepared to investigate their
      effect on glucose metabolism, glucose-dependent insulinotropic polypeptide (GIP),
      and glucagon-like peptide 1 (GLP-1) secretion, and digestion. METHODS: In study
      1, seven healthy individuals were enrolled in a four-period crossover study.
      Participants drank or ate hot water, synthesized broth, hot water with rice, and
      synthesized broth with rice. Plasma glucose, serum insulin, plasma glucagon,
      plasma GIP, and plasma GLP-1 were measured at baseline and after ingestion. In
      study 2, 6 of the 7 individuals ingested rice steamed with 13C-labeled sodium
      acetate with hot water or synthesized broth to estimate gastric emptying by the
      13C-labeled acetate breath test in a two-period crossover trial. RESULTS:
      Ingesting water or synthesized broth alone elicited no change in plasma glucose
      or serum insulin levels. Ingesting synthesized broth with rice resulted in a
      rapid rise in plasma glucose and GLP-1 (P = 0.01 and 0.02, respectively) in an
      early postprandial phase compared with that by ingesting water with rice, but the
      area under the curve of those showed no significant differences. Ingesting
      synthesized broth with rice resulted in a significantly higher gastric emptying
      coefficient than that after rice with water (P = 0.03). CONCLUSIONS: Three amino
      acids and sodium chloride corresponding to those found in actual broth promoted
      gastric emptying and led to a rapid response of plasma glucose. Our findings
      suggest that ingestion of the broth of dried kelp and dried bonito may improve
      gastric motility.

PMID- 29031771
TI  - A nonrandomized controlled clinical pilot trial on 8 wk of intermittent fasting
      (24 h/wk).
AB  - OBJECTIVE: The aim of the study was to evaluate whether intermittent fasting (IF)
      is an effective preventive measure, and whether it is feasible for healthy
      volunteers under every day conditions. METHODS: A nonrandomized controlled
      clinical trial on IF was performed with healthy volunteers over a period of 8 wk,
      and a subsequent 4-mo follow-up. Outcomes were assessed at baseline, after 8 wk,
      and after 6 mo. Volunteers who were not interested in fasting served as a control
      group. Participants in the fasting group were asked to continue their regular
      nutritional habits on the nonfasting days, whereas the control group maintained
      their habitual nutrition throughout the whole period. Outcomes included changes
      of metabolic parameters (insulin, glucose, insulin resistance, insulin-like
      growth factor-1, brain-derived neurotropic factor, lipids, liver enzymes,
      hemoglobin A1c) and coagulation markers; bioelectrical impedance analysis; body
      mass index; abdominal girth; blood pressure; general quality of life (five-item
      World Health Organization Well-Being Index [WHO-5] questionnaire), as well as
      mood and anxiety (Hospital Anxiety and Depression Scale [HADS], Profile of Mood
      States, Flourishing-Scale, visual analog scale, Likert scales). The intervention
      consisted of a fasting day, which was repeated every week for 8 wk, with
      abstinence from solid food between 00:00 and 23:59 at minimum and a maximum
      caloric intake of 300 kcal on each fasting day. A per-protocol analysis was
      performed. P < 0.05 was considered significant. RESULTS: Thirty-six volunteers
      were included; 22 allocated themselves to the fasting group, and 14 to the
      control group. Thirty-three data sets were included in the final analysis.
      Although significant in-group changes were observed in both groups for a number
      of outcomes after 8 wk and 6 mo, no significant between-group differences were
      observed for any outcome other than overall body fat mass after 8 wk as well as
      for the HADS total score and the WHO-5 total score after 6 mo, all in favor of
      the fasting group. However, none of the between-group differences were clinically
      relevant. CONCLUSIONS: We did not find any clinically relevant differences
      between groups in this controlled clinical pilot trial of 8 wk of IF in healthy
      volunteers. Further clinical research in this field is warranted to further
      analyze mechanisms and effects of IF.

PMID- 29031772
TI  - Identification and comparative profiling of ovarian and testicular microRNAs in
      the swimming crab Portunus trituberculatus.
AB  - MicroRNAs (miRNAs) are a class of endogenous non-coding small RNA, known as key
      post-transcriptional regulators for development and function of reproductive
      organ in animals. However, limited information is currently available on the
      regulatory roles of miRNAs in crustacean reproduction. In the present study, we
      performed small RNA deep sequencing in ovary and testis tissues of the swimming
      crab Portunus trituberculatus, which is a commercially important species in East
      Asian countries, to identify and characterize the miRNAs in gonads. We obtained
      187 and 225 miRNAs from ovary and testis, respectively, including 188 known and
      65 novel miRNAs. Expression profiling of the identified miRNAs indicated that
      ovary and testis shared the same six most abundant miRNAs (let-7, let-7c, let-7f,
      mir-2, mir-184 and mir-276), which accounted for a large proportion of total
      reads in gonads (35.78% for ovary and 37.01% for testis) and indicated that they
      may play essential roles in gonadal development and function. Statistically, 75
      miRNAs showed differential expression level between ovary and testis tissues, and
      the putative target genes of these miRNAs were significantly enriched in 14 KEGG
      pathways, including several pathways important in reproduction, such as GnRH
      signaling pathway, Wnt signaling pathway, ovarian steroidogenesis and TGF-beta
      signaling pathway. Further analysis found that the differentially expressed
      miRNAs exhibited stage-specific expression during ovarian and testicular
      development, suggesting their potential roles in reproductive development. Our
      study provided the first insight into regulatory roles of gonadal miRNAs and
      would serve as a valuable resource for investigating miRNA-mediated mechanisms of
      reproduction regulation in P. trituberculatus and other crustaceans.

PMID- 29031773
TI  - Identification of CDAN1, C15ORF41 and SEC23B mutations in Chinese patients
      affected by congenital dyserythropoietic anemia.
AB  - Congenital dyserythropoietic anaemias (CDAs) are a group of rare haematological
      disorders characterized by ineffective erythropoiesis and dyserythropoiesis and
      reduced numbers of red cells, often with an abnormal morphology. Pathogenic
      defects in CDAN1, C15ORF41, SEC23B, KIF23, KLF1 and GATA1 genes have been
      identified in CDAs patients. In this study, we described 13 unrelated Chinese
      CDAs patients and identified 21 mutations, including 5 novel mutations in CDAN1
      gene, and 5 novel mutations in SEC23B gene. Additionally, we predicted the
      molecular consequence of these missense mutations with Polymorphism Phenotyping
      v2 (Polyphen), Sorting Intolerant From Tolerant (SIFT), MutPred
      (http://mutpred1.mutdb.org/) and Protein Variation Effect Analyzer (Provean,
      http://provean.jcvi.org/seq_submit.php) and analyzed the conservation of the
      mutated amino acid among proteins from several mammalian species.

PMID- 29031774
TI  - The evolution of apolipoprotein B and its mRNA editing complex. Does the lack of
      editing contribute to hypertriglyceridemia?
AB  - The evolution of apolipoprotein B (Apob) has been intensely researched due to its
      importance during lipid transport. Mammalian full-length apob100 can be post
      transcriptionally edited by the enzyme apolipoprotein B mRNA editing enzyme,
      catalytic polypeptide-like complex-one (Apobec1) resulting in a truncated Apob,
      known as Apob48. Whilst both full-length and truncated forms of Apob are
      important for normal lipid homeostasis in mammals, there is no evidence for the
      presence of apob mRNA editing prior to the divergence of the mammals, yet, non
      mammalian vertebrates appear to function normally with only Apob100. To date, the
      majority of the research carried out in non-mammalian vertebrates has focused on
      chickens with only a very limited number examining apob mRNA editing in fish.
      This study focused on the molecular evolution of Apobec1 and Apob in order to
      ascertain if apob mRNA editing occurs in eels, a basal teleost which represents
      an evolutionarily important animal group. No evidence for the presence of Apobec1
      or the ability for eel apob to be edited was found. However, an important link
      between mutant mice and the evident hypertriglyceridemia in the plasma of non
      mammalian vertebrates was made. This study has provided imperative evidence to
      help bridge the evolutionary gap between fish and mammals and provides further
      support for the lack of apob mRNA editing in non-mammalian vertebrates.

PMID- 29031775
TI  - Analysis of the meiotic transcriptome reveals the genes related to the regulation
      of pollen abortion in cytoplasmic male-sterile pepper (Capsicum annuum L.).
AB  - CMS, which refers to the inability to generate functional pollen grains while
      still producing a normal gynoecium, has been widely used for pepper hybrid seed
      production. Pepper line 8214A is an excellent CMS line exhibiting 100% male
      sterility and superior economic characteristics. A TUNEL assay revealed the
      nuclear DNA is damaged in 8214A PMCs during meiosis. TEM images indicated that
      the 8214A PMCs exhibited asynchronous meiosis after prophase I, and some PMCs
      degraded prematurely with morphological features typical of PCD. Additionally, at
      the end of meiosis, the 8214A PMCs formed abnormal non-tetrahedral tetrads that
      degraded in situ. To identify the genes involved in the pollen abortion of line
      8214A, the transcriptional profiles of the 8214A and the 8214B anthers (i.e.,
      from the fertile maintainer line) during meiosis were analyzed using an RNA-seq
      approach. A total of 1355 genes were determined to be differentially expressed,
      including 424 and 931 up- and down- regulated genes, respectively, in the 8214A
      anthers during meiosis relative to the expression levels in the 8214B. The
      expression levels of ubiquitin ligase and cell cycle-related genes were
      apparently down-regulated, while the expression of methyltransferase genes was up
      regulated in the 8214A anthers during meiosis, which likely contributed to the
      PCD of these PMCs during meiosis. Thus, our results may be useful for revealing
      the molecular mechanism regulating the pollen abortion of CMS pepper.

PMID- 29031776
TI  - The HACD4 haplotype as a risk factor for atherosclerosis in males.
AB  - The 9p21.3 region is rich in regulatory elements and the variants in this region
      had been robustly associated with carotid plaque (CP) and coronary artery disease
      (CAD). Recently, the HACD4 was detected as one of the six 9p21.3 differentially
      expressed genes associated with accelerated atherosclerosis and greater mean
      lesion area in the Athsq1 congenic mice. We aimed to investigate association of
      two potentially regulatory HACD4 variants (rs36212560 I/D, rs2275888 T/C) and
      their haplotypes with CP occurrence and the level of HACD4 and FOCAD mRNA in
      human CP tissue. Association study was replicated in CAD patients who suffered
      the first myocardial infarction. Study included 477 CP patients, 303 healthy
      controls and replication sample of 224 CAD males from the population of Serbia.
      Genotypes were determined by polymerase chain reaction (PCR) and real-time PCR
      using TaqMan(r) technology. The gene expression was detected with TaqMan(r)
      technology. We have found significant and independent association of DT haplotype
      with CP presence in men (adjusted OR=1.64 CI=1.12-2.42, p=0.011). The result was
      replicated in CAD males (adjusted OR=1.84 CI=1.21-2.80, p=0.004). We have found
      significant effect of the HACD4 rs2275888 on FOCAD mRNA level in human CP tissue.
      Correction for multiple testing was performed. Independent association of HACD4
      haplotypes with atherosclerotic phenotypes connotes a further validation and
      replication in larger cohorts as well as functional studies to enlighten the
      potential mechanism of its action in pathophysiology of atherosclerosis.

PMID- 29031777
TI  - New applications of CRISPR/Cas9 system on mutant DNA detection.
AB  - The detection of mutant DNA is critical for precision medicine, but low-frequency
      DNA mutation is very hard to be determined. CRISPR/Cas9 is a robust tool for in
      vivo gene editing, and shows the potential for precise in vitro DNA cleavage.
      Here we developed a DNA mutation detection system based on CRISPR/Cas9 that can
      detect gene mutation efficiently even in a low-frequency condition. The system of
      CRISPR/Cas9 cleavage in vitro showed a high accuracy similar to traditional T7
      endonuclease I (T7E1) assay in estimating mutant DNA proportion in the condition
      of normal frequency. The technology was further used for low-frequency mutant DNA
      detection of EGFR and HBB somatic mutations. To the end, Cas9 was employed to
      cleave the wild-type (WT) DNA and to enrich the mutant DNA. Using amplified
      fragment length polymorphism analysis (AFLPA) and Sanger sequencing, we assessed
      the sensitivity of CRISPR/Cas9 cleavage-based PCR, in which mutations at 1%-10%
      could be enriched and detected. When combined with blocker PCR, its sensitivity
      reached up to 0.1%. Our results suggested that this new application of
      CRISPR/Cas9 system is a robust and potential method for heterogeneous specimens
      in the clinical diagnosis and treatment management.

PMID- 29031779
TI  - Extended adjuvant therapy: the role of subset analyses.

PMID- 29031780
TI  - Towards plasma-like collisionless trajectories in the brain.
AB  - Plasma studies depict collisionless, collective movements of charged particles.
      In touch with these concepts, originally developed by the far-flung branch of
      high energy physics, here we evaluate the role of collective behaviors and long
      range functional couplingsof charged particlesin brain dynamics. We build a
      novel, empirically testable, brain model which takes into account collisionless
      movements of charged particles in a system, the brain, equipped with
      oscillations. The model is cast in a mathematical fashion with the potential of
      being operationalized, because it can be assessed in terms of McKean-Vlasov
      equations, derived from the classical Vlasov equations for plasma. A plasma-like
      brain also elucidates cortical phase transitions in the context of a brain at the
      edge of chaos, describing the required order parameters. In sum, showing how the
      brain might exhibit plasma-like features,we go through the concept of holistic
      behavior of nervous functions.

PMID- 29031778
TI  - Extended adjuvant aromatase inhibition after sequential endocrine therapy (DATA):
      a randomised, phase 3 trial.
AB  - BACKGROUND: The effect of extended adjuvant aromatase inhibition in hormone
      receptor-positive breast cancer after sequential endocrine therapy of tamoxifen
      followed by an aromatase inhibitor for a 5-year treatment period still needs
      clarification. To address this issue, we began the DATA study to assess different
      durations of anastrozole therapy after tamoxifen. METHODS: DATA was a
      prospective, randomised, open-label, multicentre, phase 3 study done in 79
      hospitals in the Netherlands. We randomly assigned postmenopausal women with
      hormone receptor-positive early breast cancer with no signs of disease recurrence
      after 2-3 years of adjuvant tamoxifen to either 3 or 6 years of anastrozole
      treatment (1 mg orally once a day) in a 1:1 ratio. We used TENALEA (Trans
      European Network for Clinical Trials Services) for the randomisation procedure.
      Stratification factors were nodal status, hormone receptor status, HER2 status,
      and tamoxifen treatment duration. The primary study endpoint of this analysis was
      disease-free survival starting beyond 3 years after randomisation (adapted
      disease-free survival). Here we report the final analysis from the DATA trial,
      which is registered with ClinicalTrials.gov, number NCT00301457. FINDINGS:
      Between June 28, 2006, and Aug 10, 2009, we screened 1912 patients of whom 955
      were assigned to the 3-year group and 957 to the 6-year anastrozole treatment
      group. 1860 patients were eligible (931 in the 6-year group and 929 in the 3-year
      group) and 1660 were disease free 3 years after randomisation. The 5-year adapted
      disease-free survival was 83.1% (95% CI 80.0-86.3) in the 6-year group and 79.4%
      (76.1-82.8) in the 3-year group (hazard ratio [HR] 0.79 [95% CI 0.62-1.02];
      p=0.066). Patients in the 6-year treatment group had more adverse events than
      those in the 3-year treatment group, including all-grade arthralgia or myalgia
      (478 [58%] of 827 in the 6-year treatment group vs 438 [53%] of 833 in the 3-year
      treatment group) and osteopenia or osteoporosis (173 [21%] vs 137 [16%]).
      INTERPRETATION: We cannot recommend the use of extended adjuvant aromatase
      inhibition after 5 years of sequential endocrine therapy in all postmenopausal
      women with hormone receptor-positive breast cancer. FUNDING: AstraZeneca.

PMID- 29031781
TI  - The effectiveness of istradefylline for the treatment of gait deficits and
      sleepiness in patients with Parkinson's disease.
AB  - PURPOSE: Istradefylline is useful in treating the wearing-off state in
      Parkinson's disease (PD). We investigated the effectiveness of istradefylline
      (ISD) in improving arousal, sleep, and gait deficits in patients with PD.
      METHODS: We examined 14 patients with PD treated with ISD. We assessed the
      patients using the Unified Parkinson's Disease Rating Scale, Parkinson's Disease
      Questionnaire, Timed Up-and-Go test (TUG), Freezing of Gait Questionnaire (FOG
      Q), Epworth Sleepiness Scale (ESS), and Parkinson's Disease Sleep Scale (PDSS)
      before and 1 month after ISD use. RESULTS: ESS scores were significantly lower 1
      month after the start of ISD treatment (6.79+/-6.50) than before the intervention
      (8.14+/-6.15, Wilcoxon signed-rank test, p=0.0033). PDSS scores were not
      significantly different 1 month after beginning the treatment (112+/-23mm) when
      compared to those before the intervention (110+/-27mm, Wilcoxon signed-rank test,
      p=0.40). TUG scores were not changed after 1 month of ISD use (14.9+/-8.3s) when
      compared to those before the intervention (21.3+/-30.0s, Wilcoxon signed-rank
      test, p=0.59). Although these measures were not significantly affected by ISD
      treatment, some patients remarkably improved after the treatment. FOG-Q scores
      were significantly lower 1 month after the beginning of treatment (9.79+/-7.16)
      than those before the intervention (12.14+/-5.82, Wilcoxon signed-rank test,
      p=0.030). CONCLUSIONS: ISD may improve daytime sleepiness and FOG in patients
      with PD.

PMID- 29031782
TI  - Editorial.

PMID- 29031783
TI  - Antidiabetic effect of Achillea millefollium through multitarget interactions:
      alpha-glucosidases inhibition, insulin sensitization and insulin secretagogue
      activities.
AB  - ETHNOPHARMACOLOGICAL IMPORTANCE: Achillea millefolium L. (Asteraceae) is a
      perennial herb used in Mexican folk medicine for treatment of several
      pathologies, including inflammatory and spasmodic gastrointestinal disorders,
      hepatobiliary complaints, overactive cardiovascular, respiratory ailments and
      diabetes. AIM OF THE STUDY: To evaluate the potential antidiabetic effect in vivo
      and to establish the potential mode of action through in vitro approaches of
      Achillea millefolium. MATERIALS AND METHODS: The antidiabetic effect of
      hydroalcoholic extract of Achillea millefolium (HAEAm) was evaluated on the oral
      glucose tolerance tests, in normoglycemic and experimental Type 2 diabetic mice
      models. In addition, we evaluated the possible mode of action in in vitro assays
      to determine alpha-glucosidases inhibition, the insulin secretion and calcium
      mobilization in RINm5F cells and PPARgamma and GLUT4 expression in 3T3-L1 cells.
      RESULTS: HAEAm showed significant glucose diminution on oral glucose tolerance
      test and in acute experimental Type 2 diabetic assay with respect to the control
      (p < 0.05). In addition, HAEAm promoted the alpha-glucosidases inhibition by 55%
      at 1mg/ml respect to control. On the other hand, HAEAm increased the PPARgamma
      (five-times) and GLUT4 (two-fold) relative expression than control (p < 0.05).
      Finally, HAEAm significantly increased the insulin secretion and [Ca2+]i compared
      with control. CONCLUSION: The HAEAm possesses in vivo antidiabetic effect, having
      such effect through multitarget modes of action that involve antihyperglycemic
      (alpha-glucosidases inhibition), hypoglycemic (insulin secretion) and potential
      insulin sensitizer (PPARgamma/GLUT4 overexpression) actions.

PMID- 29031784
TI  - Isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics for
      the investigation of the effect of Hugan Qingzhi on non-alcoholic fatty liver
      disease in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Hugan Qingzhi tablet (HQT), a traditional Chinese
      medicine formula has been adopted for preventing and treating nonalcoholic fatty
      liver disease (NAFLD). AIM: In order to explore the anti-NAFLD mechanisms of HQT,
      iTRAQ-based proteomic was employed to investigate the expression profiles of
      proteins in NAFLD rats induced by high-fat diet after HQT treatment. MATERIALS
      AND METHODS: The NAFLD rat model was administrated with high-fat diet (HFD) for
      12weeks. HQT was administrated in a daily basis to the HFD groups. Biochemical
      markers, liver histology, pro-inflammatory cytokines, and oxidative
      stress/antioxidant biomarkers were assayed to evaluate HQT effects in HFD-induced
      NAFLD rats. Furthermore, the combined strategy of iTRAQ labeling with strong
      cation exchange-non-liquid chromatography-tandem mass spectrometry (SCX-non-LC
      MS/MS) analysis were employed to explore the mechanisms of HQT's protective
      effect against NAFLD in rats. Western blotting was performed to verify the
      proteomic results. RESULTS: The histopathologic characteristics and biochemical
      data showed that HQT exhibited protective effects on HFD-induced NAFLD rats.
      After being analyzed by the combined strategy of iTRAQ with LC-MS/MS and
      subsequent investigation, we identified 275 differentially expressed proteins in
      the HFD group, compared to the control; 207 altered proteins in the HQT high dose
      + HFD group, compared to the HFD group; and 316 altered proteins in the HQT high
      dose + HFD group, compared to the control. Based on the Kyoto Encyclopedia of
      Gene and Genomes (KEGG) pathway mapping, the conclusion has reached that several
      pathways including microbial metabolism in diverse environments, fatty acid
      metabolism, inflammatory response, oxidative stress, bile secretion, and
      peroxisome proliferator activated receptor (PPAR) signaling pathway were closely
      related to the effects of HQT in HFD-induced NAFLD in rats. Furthermore, several
      differentially expressed proteins, including phytanoyl-CoA 2-hydroxylase (PHYH),
      acyl-CoA synthetase 1 long chain (ACSL1), hemopexin, Alpha-1-acid glycoprotein
      (ORM1), fatty acid binding protein 4 (FABP4), soluble sulphotransferase 2a1
      (Sult2a1), and argininosuccinate synthase 1 (ASS1) were verified by the western
      blotting analysis and these results were consistent with the data obtained from
      the proteomics analysis. CONCLUSIONS: Our results not only confirm that Hugan
      Qingzhi exhibits a significant protective effect in HFD-induced NAFLD rats but
      also provide a better understanding for the treatments of NAFLD.

PMID- 29031785
TI  - Previous Mental Disorders and Subsequent Onset of Chronic Back or Neck Pain:
      Findings From 19 Countries.
AB  - : Associations between depression/anxiety and pain are well established, but its
      directionality is not clear. We examined the associations between temporally
      previous mental disorders and subsequent self-reported chronic back/neck pain
      onset, and investigated the variation in the strength of associations according
      to timing of events during the life course, and according to gender. Data were
      from population-based household surveys conducted in 19 countries (N = 52,095).
      Lifetime prevalence and age of onset of 16 mental disorders according to the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and the
      occurrence and age of onset of back/neck pain were assessed using the Composite
      International Diagnostic Interview. Survival analyses estimated the associations
      between first onset of mental disorders and subsequent back/neck pain onset. All
      mental disorders were positively associated with back/neck pain in bivariate
      analyses; most (12 of 16) remained so after adjusting for psychiatric
      comorbidity, with a clear dose-response relationship between number of mental
      disorders and subsequent pain. Early-onset disorders were stronger predictors of
      pain; when adjusting for psychiatric comorbidity, this remained the case for
      depression/dysthymia. No gender differences were observed. In conclusion,
      individuals with mental disorder, beyond depression and anxiety, are at higher
      risk of developing subsequent back/neck pain, stressing the importance of early
      detection of mental disorders, and highlight the need of assessing back/neck pain
      in mental health clinical settings. PERSPECTIVE: Previous mental disorders
      according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition are positively associated with subsequent back/neck pain onset, with a
      clear dose-response relationship between number of mental disorders and
      subsequent pain. Earlier-onset mental disorders are stronger predictors of
      subsequent pain onset, compared with later-onset disorders.

PMID- 29031786
TI  - Differentiation and Protective Capacity of Virus-Specific CD8+ T Cells Suggest
      Murine Norovirus Persistence in an Immune-Privileged Enteric Niche.
AB  - Noroviruses can establish chronic infections with active viral shedding in
      healthy humans but whether persistence is associated with adaptive immune
      dysfunction is unknown. We used genetically engineered strains of mouse norovirus
      (MNV) to investigate CD8+ T cell differentiation during chronic infection. We
      found that chronic infection drove MNV-specific tissue-resident memory (Trm) CD8+
      T cells to a differentiation state resembling inflationary effector responses
      against latent cytomegalovirus with only limited evidence of exhaustion. These
      MNV-specific Trm cells remained highly functional yet appeared ignorant of
      ongoing viral replication. Pre-existing MNV-specific Trm cells provided partial
      protection against chronic infection but largely ceased to detect virus within 72
      hours of challenge, demonstrating rapid sequestration of viral replication away
      from T cells. Our studies revealed a strategy of immune evasion by MNV via the
      induction of a CD8+ T cell program normally reserved for latent pathogens and
      persistence in an immune-privileged enteric niche.

PMID- 29031787
TI  - Assessing prediction accuracy for outcomes of ventilator-associated events and
      infections in critically ill children: a prospective cohort study.
AB  - OBJECTIVES: To assess the prediction accuracy of the 2008 US Centers for Disease
      Control and Prevention (CDC) definitions for ventilator-associated pneumonia
      (VAP)/ventilator-associated tracheobronchitis (VAT), 2013 CDC definitions for
      ventilator-associated events (VAE) and a new VAE algorithm in the paediatric
      (Ped) population, the Ped-VAE. METHODS: We performed a prospective 13-month
      cohort study at a multidisciplinary paediatric intensive care unit (PICU).
      Primary endpoints were duration of ventilation episode, PICU or hospitalization
      length of stay from episode and episode mortality. Episodes without VAE (or
      VAP/VAT) served as comparison groups. RESULTS: One hundred eight episodes of
      ventilation (99 children) with 2554 ventilator-days were assessed. In episodes
      not meeting 2008 CDC definitions, a median of 6 ventilator-days (PICU stay 11
      days) was documented (with eight deaths), not significantly different from
      episodes not meeting VAE or Ped-VAE definitions. Using 2008 CDC criteria, 11
      (10.2%) respiratory infections (eight tracheobronchitis) were identified, seven
      VAEs using 2013 CDC criteria (6.4%) and 29 (26.8%) using Ped-VAE criteria
      (relative risk vs. 2008 CDC criteria 2.58; 95% confidence interval 1.36-4.91). In
      contrast with their comparison groups, episodes meeting 2008 CDC criteria did not
      significantly predict outcomes, whereas VAEs (only four possible VAPs) were
      associated with significantly more ventilation and PICU length of stay (12-day/8
      day increase) and sevenfold increase in mortality. Ped-VAE did not increase
      mortality, but it was associated with 4-day increase in ventilation and PICU
      length of stay, with ten possible VAPs, and atelectasis (9/12) as the main
      paediatric ventilator-associated condition. CONCLUSIONS: The 2008 CDC criteria
      did not predict outcomes, whereas VAE only identified very severe events. The Ped
      VAE algorithm had more accuracy predicting outcomes by characterizing lower
      oxygenation changes and identifying hypoxaemia severity, a major driver of
      management.

PMID- 29031788
TI  - Susceptibility testing of Kingella kingae to cefazolin.

PMID- 29031790
TI  - What are "Purkinje" cells? And do they have a role in the genesis of atrial
      fibrillation?

PMID- 29031789
TI  - Trends and differences in tuberculosis incidences and clustering among natives in
      Denmark, Sweden and Finland: comparison of native incidences and molecular
      epidemiology among three low-incidence countries.
AB  - OBJECTIVES: To compare the epidemiology of tuberculosis (TB) in Denmark, Sweden
      and Finland, by focusing on the native population in order to identify
      epidemiologic differences and thus indirectly possible differences in TB control.
      METHODS: TB incidence trends from 1990 through 2015 were compared among the
      countries. In addition, for the periods 2012-2013 and 2014-2015, genotyping data
      were compared. Genotyping was performed using the 24-locus mycobacterial
      interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) method
      in Denmark and Sweden. For Finland, spoligotyping in conjunction with the 15
      locus MIRU-VNTR method was used for 2012-2013 and translated into the 24-locus
      MIRU-VNTR when feasible, and for 2014-2015 only MIRU-VNTR was used. Both
      incidence trends and molecular epidemiology were assessed for native cases.
      RESULTS: The average annual rate of change in TB incidence for native Danes was 
      2.4% vs. -6.1% and -6.9% for native Swedes and Finns respectively. In 2012-2013
      Denmark had 52 native cases in the largest transmission chain vs. three cases in
      Sweden and ten in Finland, and during the same period the clustering rate for
      native Danes was 48.8% vs. 6.5% and 18.2% for native Swedes and Finns
      respectively. For 2014-2015, a similar pattern was seen. CONCLUSIONS: The decline
      of TB among natives in Denmark is slower than for Sweden and Finland, and it
      seems Denmark has more active transmission among natives. The focused assessment
      on basic native TB epidemiology reveals striking differences in TB transmission
      among otherwise similar low-TB-incidence countries.

PMID- 29031791
TI  - Biofeedback in dysphonia - progress and challenges.
AB  - INTRODUCTION: There is evidence that all the complex machinery involved in speech
      acts along with the auditory system, and their adjustments can be altered.
      OBJECTIVE: To present the evidence of biofeedback application for treatment of
      vocal disorders, emphasizing the muscle tension dysphonia. METHODS: A systematic
      review was conducted in Scielo, Lilacs, PubMed and Web of Sciences databases,
      using the combination of descriptors, and admitting as inclusion criteria:
      articles published in journals with editorial committee, reporting cases or
      experimental or quasi-experimental research on the use of biofeedback in real
      time as additional source of treatment monitoring of muscle tension dysphonia or
      for vocal training. RESULTS: Thirty-three articles were identified in databases,
      and seven were included in the qualitative synthesis. The beginning of
      electromyographic biofeedback studies applied to speech therapy were promising
      and pointed to a new method that enabled good results in muscle tension
      dysphonia. Nonetheless, the discussion of the results lacked physiological
      evidence that could serve as their basis. The search for such explanations has
      become a challenge for speech therapists, and determined two research lines: one
      dedicated to the improvement of the electromyographic biofeedback methodology for
      voice disorders, to reduce confounding variables, and the other dedicated to the
      research of neural processes involved in changing the muscle engram of normal and
      dysphonic patients. CONCLUSION: There is evidence that the electromyographic
      biofeedback promotes changes in the neural networks responsible for speech, and
      can change behavior for vocal emissions with quality.

PMID- 29031792
TI  - Control of myogenic tone and agonist induced contraction of intramural coronary
      resistance arterioles by cannabinoid type 1 receptors and endocannabinoids.
AB  - It was tested whether intrinsic CB1R activation modifies myogenic and agonist
      induced contraction of intramural coronary resistance arteries of the rat. CB1R
      protein was detected by immuno-histochemistry and by Western blot, its mRNA by
      qRT-PCR in their wall. Microsurgically prepared cylindrical coronary segments
      (~100-150MUm) developed myogenic contraction (~20% of relaxed luminal diameter),
      from which a substantial relaxation (~15%) in response to WIN55212 (a specific
      agonist of the CB1Rs) has been found. CB1R-mediated relaxation was blocked by
      O2050 and AM251 (neutral antagonist and inverse agonist of the CB1R,
      respectively) and was partially blocked by the NO synthase blocker Nomega-nitro-L
      arginine. CB1R blockade enhanced myogenic tone and augmented AngII-induced
      vasoconstriction (from 17.8+/-1.2 to 29.1+/-2.9%, p<0.05). Inhibition of
      diacylglycerol lipase by tetrahydrolipstatin, (inhibitor of endogenous 2-AG
      production) also augmented coronary vasoconstriction. These observations prove
      that vascular endocannabinoids are significant negative modulators of the
      myogenic and agonist-induced tone of intramural coronary arterioles acting
      through CB1Rs.

PMID- 29031793
TI  - The Role of Anchoring in Working Up Diarrhea: A Practical Teaching Case.

PMID- 29031794
TI  - Biophysics in Canada.

PMID- 29031795
TI  - Pulmonary sequelae and functional limitations in children and adults with
      bronchopulmonary dysplasia.
AB  - Preterm infants with bronchopulmonary dysplasia (BPD) often suffer from life-long
      pulmonary impairments in pulmonary physical function. This review summarizes our
      current understanding of the chronic pulmonary impairments and physical
      functional limitations associated with BPD from preterm birth to adulthood. It
      also identifies opportunities for intervention in children and adults living with
      chronic lung disease (CLD) after preterm birth.

PMID- 29031796
TI  - Peptide welding technology - A simple strategy for generating innovative ligands
      for G protein coupled receptors.
AB  - Based on their high selectivity of action and low toxicity, naturally occurring
      peptides have great potential in terms of drug development. However, the
      pharmacokinetic properties of peptides, in particular their half life, are poor.
      Among different strategies developed for reducing susceptibility to peptidases,
      and thus increasing the duration of action of peptides, the generation of
      branched peptides has been described. However, the synthesis and purification of
      branched peptides are extremely complicated thus limiting their druggability.
      Here we present a novel and facile synthesis of tetrabranched peptides acting as
      GPCR ligands and their in vitro and vivo pharmacological characterization.
      Tetrabranched derivatives of nociceptin/orphanin FQ (N/OFQ), N/OFQ related
      peptides, opioid peptides, tachykinins, and neuropeptide S were generated with
      the strategy named peptide welding technology (PWT) and characterized by high
      yield and purity of the desired final product. In general, PWT derivatives
      displayed a pharmacological profile similar to that of the natural sequence in
      terms of affinity, pharmacological activity, potency, and selectivity of action
      in vitro. More importantly, in vivo studies demonstrated that PWT peptides are
      characterized by increased potency associated with long lasting duration of
      action. In conclusion, PWT derivatives of biologically active peptides can be
      viewed as innovative pharmacological tools for investigating those conditions and
      states in which selective and prolonged receptor stimulation promotes beneficial
      effects.

PMID- 29031797
TI  - Impact of zero-valent iron nanoparticles on the activity of anaerobic granular
      sludge: From macroscopic to microcosmic investigation.
AB  - The study aimed at evaluating the influence of nano zero-valent iron (nZVI) on
      the activity of anaerobic granular sludge (AGS) from both macroscopic and
      microcosmic aspects using different methodologies. The tolerance response of AGS
      to nZVI was firstly investigated using short-term and long-term experiments, and
      also compared with anaerobic flocs. The Fe fate and distribution, the change of
      contents/structure of extracellular polymeric substances (EPS), and the variation
      of microbial community in the AGS after exposure to nZVI were further explored.
      Contrary to the anaerobic floc, insignificant inhibition of nZVI at dosage lower
      than 30 mmoL/L on the activity of AGS was observed. Additionally, the extra
      hydrogen gas released from the oxidation of nZVI was presumably suggested to
      stimulate the hydrogenotrophic methanogenesis process, resulting in 30% methane
      production enhancement when exposure to 30 mmoL/L nZVI. The microscopic analysis
      indicated that nZVI particles were mainly adsorbed on the surface of AGS in the
      form of iron oxides aggregation without entering into the interior of the
      granule, protecting most cells from contact damage. Moreover, surrounded EPS
      located outer surface of anaerobic granule could react with nZVI to accelerate
      the corrosion of nZVI and slow down H2 release from nZVI dissolution, thus
      further weakening the toxicity of nZVI to anaerobic microorganisms. The decrease
      in bacteria involved in glucose degradation and aceticlastic methanogens as well
      as the increase of hydrogenotrophic methanogens indicated a H2 mediated shift
      toward the hydrogenotrophic pathway enhancing the CH4 production.

PMID- 29031798
TI  - Viral diversity and abundance in polluted waters in Kampala, Uganda.
AB  - Waterborne viruses are a significant cause of human disease, especially in
      developing countries such as Uganda. A total of 15 virus-selective samples were
      collected at five sites (Bugolobi Wastewater Treatment Plant (WWTP) influent and
      effluent, Nakivubo Channel upstream and downstream of the WWTP, and Nakivubo
      Swamp) in July and August 2016. Quantitative PCR and quantitative RT-PCR was
      performed to determine the concentrations of four human viruses (adenovirus,
      enterovirus, rotavirus, and hepatitis A virus) in the samples. Adenovirus
      (1.53*105-1.98*107 copies/L) and enterovirus (3.17*105-8.13*107 copies/L) were
      found to have the highest concentrations in the samples compared to rotavirus
      (5.79*101-3.77*103 copies/L) and hepatitis A virus (9.93*102-1.11*104 copies/L).
      In addition, next-generation sequencing and metagenomic analyses were performed
      to assess viral diversity, and several human and vertebrate viruses were
      detected, including Herpesvirales, Iridoviridae, Poxviridae, Circoviridae,
      Parvoviridae, Bunyaviridae and others. Effluent from the wastewater treatment
      plant appears to impact surface water, as samples taken from surface water
      downstream of the treatment plant had higher viral concentrations than samples
      taken upstream. Temporal fluctuations in viral abundance and diversity were also
      observed. Continuous monitoring of wastewater may contribute to assessing viral
      disease patterns at a population level and provide early warning of potential
      outbreaks using wastewater-based epidemiology methods.

PMID- 29031799
TI  - Impact of humic acid on the photoreductive degradation of perfluorooctane
      sulfonate (PFOS) by UV/Iodide process.
AB  - Iodide photolysis under UV illumination affords an effective method to produce
      hydrated electrons (eaq-) in aqueous solution. Therefore, UV/Iodide photolysis
      can be utilized for the reductive degradation of many recalcitrant pollutants.
      However, the effect of naturally occurring organic matter (NOM) such as humic and
      fulvic acids (HA/FA), which may impact the efficiency of UV/Iodide
      photoreduction, is poorly understood. In this study, the UV photoreductive
      degradation of perfluorooctane sulfonate (PFOS) in the presence of I- and HA is
      studied. PFOS undergoes a relatively slow direct photoreduction in pure water, a
      moderate level of degradation via UV/Iodide, but a rapid degradation via
      UV/Iodide/HA photolysis. After 1.5 h of photolysis, 86.0% of the initial [PFOS]
      was degraded in the presence of both I- and HA with a corresponding
      defluorination ratio of 55.6%, whereas only 51.7% of PFOS was degraded with a
      defluorination ratio of 4.4% via UV/Iodide illumination in the absence of HA. The
      relative enhancement in the presence of HA in the photodegradation of PFOS can be
      attributed to several factors: a) HA enhances the effective generation of eaq-
      due to the reduction of I2, HOI, IO3- and I3- back to I-; b) certain functional
      groups of HA (i.e., quinones) enhance the electron transfer efficiency as
      electron shuttles; c) a weakly-bonded association of I- and PFOS with HA
      increases the reaction probability; and d) absorption of UV photons by HA itself
      produces eaq-. The degradation and defluorination efficiency of PFOS by
      UV/Iodide/HA process is dependent on pH and HA concentration. As pH increases
      from 7.0 to 10.0, the enhancement effect of HA improves significantly. The
      optimal HA concentration for the degradation of 0.03 mM PFOS is 1.0 mg L-1.

PMID- 29031800
TI  - Tannic acid promotes ion release of copper oxide nanoparticles: Impacts from
      solution pH change and complexation reactions.
AB  - The increasing number of applications in which copper oxide nanoparticles (CuO
      NPs) are used, may lead to potential release of CuO NPs into the environment.
      However, the impact of natural organic matters on the behavior and fate of CuO
      NPs in aquatic media is still largely unknown. In this study, the dissolution and
      aggregation of CuO NPs under the exposure of tannic acid (TA) were monitored over
      a period of 72 h, with a focus on assessing the contributions of solution pH
      changes and complexation reactions. Results showed that the total amount of Cu2+
      released from CuO NPs increased in the presence of TA especially at the highest
      TA concentration of 73.5 MUmol/L. Although TA was observed to wrap around the CuO
      NPs, the aggregation of CuO NPs was not strongly influenced by TA and by the
      solution pH as investigated in this study. The kinetics of Cu2+ release were
      fitted using the modified pseudo second-order model and the rate of dissolution
      was assessed to be highest at TA = 14.7 MUmol/L. At pH = 4, the increased H+
      concentration was responsible for increased Cu2+ release, whereas the
      complexation reaction between Cu2+ and TA dominated at pH = 7. These findings
      suggested that the effects of TA on the dissolution of CuO NPs were a combination
      of solution pH change and complexation reaction, the relative fractions of which
      also depended on the solution pH. Additionally, the percentage of Cu2+ released
      from the CuO NPs was found to increase upon decreasing concentrations of CuO NPs.
      Our work helps to further understand how and to which extent natural organic
      matters affect the behavior and fate of CuO NPs.

PMID- 29031801
TI  - Use of lectin-magnetic separation (LMS) for detecting Toxoplasma gondii oocysts
      in environmental water samples.
AB  - Proof-of-principle of lectin-magnetic separation (LMS) for isolating Toxoplasma
      oocysts (pre-treated with 0.5% acidified pepsin (AP)) from water for subsequent
      detection by microscopy or molecular methods has been shown. However, application
      of this technique in the routine water-analysis laboratory requires that the
      method is tested, modified, and optimized. The current study describes attempts
      to apply the LMS technique on supernatants from water samples previously analyzed
      for contamination with Cryptosporidium and Giardia using standard methods, and
      the supernatant following immunomagnetic separation (IMS) retained. Experiments
      on AP-treatment of Toxoplasma oocysts in situ in such samples demonstrated that
      overnight incubation at 37  degrees C was adequate, but excess AP had to be
      removed before continuing to LMS; neutralization in sodium hydroxide and a single
      wash step was found to be suitable. Mucilaginous material in post-IMS samples
      that had been stored at room temperature without washing, which was found to be
      probably an exudate from bacterial and fungal overgrowth, hampered the isolation
      of T. gondii oocysts by LMS beads. For detection, microscopy was successful only
      for clean samples, as debris occluded viewing in dirtier samples. Although qPCR
      was successful, for some samples non-specific inhibition occurred, as
      demonstrated by inhibition of an internal amplification control in the qPCR
      reaction. For some, but not all, samples this could be addressed by dilution.
      Finally, the optimized methodology was used for a pilot project in which 23 post
      IMS water sample concentrates were analyzed. Of these, only 20 provided
      interpretable results (without qPCR inhibition) of which one sample was positive,
      and confirmed by sequencing of PCR product, indicating that Toxoplasma oocysts
      occur in Norwegian drinking water samples. In conclusion, we suggest that post
      IMS samples may be suitable for analysis for Toxoplasma oocysts using LMS, only
      if freshly processed or washed before being refrigerated. In addition,
      application of AP treatment requires a neutralization step before proceeding to
      LMS. For detection, qPCR, rather than microscopy, is the most appropriate
      approach, although some inhibition may still occur, and therefore inclusion of an
      internal amplification control is important. Our study indicates that, despite
      some limitations, this approach would be appropriate for further large-scale
      analysis of samples of raw and treated drinking water.

PMID- 29031802
TI  - Extreme levels of ambient air pollution adversely impact cardiac and central
      aortic hemodynamics: the AIRCMD-China study.
AB  - Ambient air pollution is an independent risk factor for cardiovascular diseases.
      However, the underlying mechanisms have yet to be fully elucidated. We performed
      a panel study on 65 nonsmoking patients with metabolic syndrome, with four
      repeated clinical visits between 2012 and 2013 in Beijing, China. Cardiac and
      central aortic hemodynamic parameters were measured by pulse wave analyses as
      subendocardial viability ratio, ejection duration, and central aortic pressure.
      We also calculated rate-pressure product parameter and collected peripheral blood
      for analyses. High levels of ambient particulate matter with diameter <=10 and
      2.5 MUm (PM10 and PM2.5), black carbon, sulfur dioxide, and nitrogen dioxide were
      121.3, 99.5, 6.5, 24.5, and 59.2 MUg/m3, respectively. Short- to medium-term
      exposures to high levels of ambient air pollution adversely impacted central
      hemodynamics-derived surrogates of myocardial perfusion and oxygen demand. Each
      10 MUg/m3 increase in PM2.5 was associated with significant decreases of 0.67%
      (95% confidence interval: -2.84, -0.22) in subendocardial viability ratio at
      moving average 35 days (MA35) and an increase of 0.31 in rate-pressure product
      (95% confidence interval: 0.03, 0.59) at MA5. In conclusion, our results suggest
      that impaired myocardial perfusion and increased myocardial oxygen demand may
      play importantly mechanistic roles in air pollution-attributed cardiovascular
      diseases.

PMID- 29031804
TI  - Transcriptional response after exposure to domoic acid-producing Pseudo-nitzschia
      in the digestive gland of the mussel Mytilus galloprovincialis.
AB  - Bivalve molluscs are filter feeding species that can accumulate biotoxins in
      their body tissues during harmful algal blooms. Amnesic Shellfish Poisoning (ASP)
      is caused by species of the diatom genus Pseudo-nitzschia, which produces the
      toxin domoic acid. The Mytilus galloprovincialis digestive gland transcriptome
      was de novo assembled based on the sequencing of 12 cDNA libraries, six obtained
      from control mussels and six from mussels naturally exposed to domoic acid
      producing diatom Pseudo-nitzschia australis. After de novo assembly 94,727
      transcripts were obtained, with an average length of 1015 bp and a N50 length of
      761 bp. The assembled transcripts were clustered (homology > 90%) into 69,294
      unigenes. Differential gene expression analysis was performed (DESeq2 algorithm)
      in the digestive gland following exposure to the toxic algae. A total of 1158
      differentially expressed unigenes (absolute fold change > 1.5 and p-value < 0.05)
      were detected: 686 up-regulated and 472 down-regulated. Several membrane
      transporters belonging to the family of the SLC (solute carriers) were over
      expressed in exposed mussels. Functional enrichment was performed using Pfam
      annotations obtained from the genes differentially expressed, 37 Pfam families
      were found to be significantly (FDR adjusted p-value < 0.1) enriched. Some of
      these families (sulfotransferases, aldo/keto reductases, carboxylesterases, C1q
      domain and fibrinogen C-terminal globular domain) could be putatively involved in
      detoxification processes, in the response against of the oxidative stress and in
      immunological processes. Protein network analysis with STRING algorithm found
      alteration of the Notch signaling pathway under the action of domoic acid
      producing Pseudo-nitzschia. In conclusion, this study provides a high quality
      reference transcriptome of M. galloprovincialis digestive gland and identifies
      potential genes involved in the response to domoic acid.

PMID- 29031803
TI  - The burden and correlates of hypertension among Chinese rural population in Han,
      Uygur, and Kazak: a cross-sectional study.
AB  - The present study was conducted to investigate the prevalence, awareness,
      treatment, control, and associated risk factors of hypertension among rural
      population in Xinjiang Province in Northwest China. The Cardiovascular Risk
      Survey study was conducted on a representative sample of the Northwest China
      adult population. A four-stage stratified cluster random sampling scheme was
      adopted to recruit representative samples. The data were collected by trained
      staff. Multivariable logistic regression models were used to identify the
      associated risk factors. Overall, 8295 study participants aged 35-101 years were
      enrolled. The overall hypertension prevalence was 35.01%. The prevalence of
      hypertension in Han, Uygur, and Kazak population was 36.84%, 33.32%, and 52.57%,
      respectively. The hypertension awareness, treatment, control, and control among
      treated participants were 56.1%, 44.7%, 10.9%, and 24.3%, respectively.
      Multivariate logistic regression showed that age, body mass index, central
      obesity, ethnic, and drinking status were identified as risk factors for
      hypertension. Hypertension was found to be highly prevalent in rural adults in
      Xinjiang, China, especially in Kazak population. Although the levels of
      awareness, treatment, and control have improved, it was still lower than
      developed countries. Effective measures should be adopted to promote the
      prevention and control of hypertension.

PMID- 29031805
TI  - Aptamer-targeted delivery of Bcl-xL shRNA using alkyl modified PAMAM dendrimers
      into lung cancer cells.
AB  - RNAi-based gene therapy has been recently considered as a promising approach
      against cancer. Targeted delivery of drug, gene or therapeutic RNAi-based systems
      to tumor cells is one of the important issues in order to reduce side effects on
      normal cells. Several strategies have been developed to improve the safety and
      selectivity of cancer treatments including antibodies, peptides and recently
      aptamers with various attractive characteristics including higher target
      specificity, affinity and reduced toxicity. Here we described a novel targeted
      delivery platform comprising modified PAMAM with 10-bromodecanoic acid (10C) and
      10C-PEG for improvement of transfection efficiency, AS1411 aptamer for targeting
      nucleolin ligand on target cancer cells and shRNA plasmid for specific knockdown
      of Bcl-xL protein. Modified vector could significantly improve the transfection
      efficiency even after covalent or non-covalent aptamer binding compared to the
      non-targeted vector in A549 cells. The results of gene silencing and apoptosis
      assay indicated that our targeted shRNA delivery system could efficiently down
      regulate the Bcl-xL expression up to 25% and induce 14% late apoptosis in target
      cancer cells with strong cell selectivity. This study proposed a novel targeted
      non-viral system for shRNA-mediated gene-silencing in cancer cells.

PMID- 29031806
TI  - Tumor suppressive protein phosphatases in human cancer: Emerging targets for
      therapeutic intervention and tumor stratification.
AB  - Aberrant protein phosphorylation is one of the hallmarks of cancer cells, and in
      many cases a prerequisite to sustain tumor development and progression. Like
      protein kinases, protein phosphatases are key regulators of cell signaling.
      However, their contribution to aberrant signaling in cancer cells is overall less
      well appreciated, and therefore, their clinical potential remains largely
      unexploited. In this review, we provide an overview of tumor suppressive protein
      phosphatases in human cancer. Along their mechanisms of inactivation in defined
      cancer contexts, we give an overview of their functional roles in diverse
      signaling pathways that contribute to their tumor suppressive abilities. Finally,
      we discuss their emerging roles as predictive or prognostic markers, their
      potential as synthetic lethality targets, and the current feasibility of their
      reactivation with pharmacologic compounds as promising new cancer therapies. We
      conclude that their inclusion in clinical practice has obvious potential to
      significantly improve therapeutic outcome in various ways, and should now
      definitely be pushed forward.

PMID- 29031807
TI  - Cytochrome c peroxidase regulates intracellular reactive oxygen species and
      methylglyoxal via enzyme activities of erythroascorbate peroxidase and
      glutathione-related enzymes in Candida albicans.
AB  - D-erythroascorbate peroxidase (EAPX1) deficiency causes glutathione deprivation,
      leading to the accumulation of methylglyoxal and reactive oxygen species (ROS),
      and especially, induction of cytochrome c peroxidase (Ccp1) in Candida albicans.
      Nevertheless, reciprocal effects between changes in Ccp1 activity and the
      antioxidative D-erythroascorbic acid- and glutathione-dependent redox status,
      which reflects methylglyoxal biosynthesis altering pathophysiology are unclear in
      eukaryotes. To elucidate the effect of CCP1 expression on EAPX1 and glutathione
      reductase (Glr1) activity-mediated D-erythroascorbic acid biosynthesis and redox
      homeostasis, the CCP1 gene was disrupted and overexpressed. First, we
      demonstrated both glutathione-independent and-dependent metabolite contents and
      their corresponding gene transcripts and enzyme activities (i.e., Ccp1, catalase
      peroxidase [KatG], superoxide dismutase [Sod], Eapx1, and Glr1) in CCP1 mutants.
      Second, methylglyoxal-oxidizing alcohol dehydrogenase (Adh1) and methylglyoxal
      reducing oxidoreductase activity on glycolytic methylglyoxal and pyruvate
      production and NAD(P)H content were determined in these mutants. Contrary to our
      expectation, CCP1 disruption (42.19+/-3.22nmolO2h-1mgwetcell-1) failed to affect
      cell respiration compared to the wild-type strain (41.62+/-7.11nmolO2h-1mgwetcell
      1) under cyanide treatment, and in contrast to hydrogen peroxide (H2O2) treatment
      (21.74+/-1.03nmol O2h-1mgwetcell-1). Additionally, Ccp1 predominantly detoxified
      H2O2 rather than negligible scavenging activities towards methylglyoxal and other
      oxidants. CCP1 deficiency stimulated Sod and Adh1 activity but downregulated
      Glr1, Eapx1, catalase, and peroxidase activity while enhancing KatG, EAPX1, and
      GLR1 transcription by decreasing glutathione and D-erythroascorbic acid and
      increasing pyruvate. Noticeably, the ROS-accumulating CCP1-deficient mutant
      maintained steady-state levels of methylglyoxal, which was revealed to be
      regulated by methylglyoxal-oxidizing and -reducing activity with drastic changes
      in NAD(P)H. We confirmed and clarified our results by showing that CCP1/EAPX1
      double disruptants underwent severe growth defects due to the D-erythroascorbic
      acid and glutathione depletion because of pyruvate overaccumulation. These
      observations were made in both budding and hyphal-growing CCP1 mutants. The
      revealed metabolic network involving Ccp1 and other redox regulators affected ROS
      and methylglyoxal through D-erythroascorbic acid and glutathione-dependent
      metabolites, thereby influencing dimorphism. This is the first report of the Ccp1
      mediated D-erythroascorbic acid and glutathione biosynthesis accompanying
      methylglyoxal scavengers for full fungal virulence.

PMID- 29031808
TI  - Specific disruption of contextual memory recall by sparse additional activity in
      the dentate gyrus.
AB  - The dentate gyrus (DG) of the hippocampus is essential for contextual and spatial
      memory processing. While lesion or silencing of the DG impairs contextual memory
      encoding and recall, overly activated DG also prevents proper memory retrieval.
      Abnormally elevated activity in the DG is repeatedly reported in amnesic mild
      cognitive impairment (aMCI) patients or aged adults. Although the correlation
      between memory failure and abnormally active hippocampus is clear, their causal
      relationship or the underlying nature of such interfering activity is not well
      understood. Using optogenetics aided by a carefully controlled adeno-associated
      virus infection system, we were able to examine the differential effects of
      abnormally activated hippocampus on mice motor behavior and memory function,
      depending on the extent of the stimulation. Optogenetic stimulation of massive
      proportion of dorsal DG cells resulted in memory retrieval impairment, but also
      induced increase in general locomotion. Random additional activity in a sparse
      population of dorsal DG neurons, however, interfered with contextual memory
      recall without inducing hyperactivity. Our findings thus establish the causal
      role of elevated DG activity on memory recall failure, suggesting such aberrant
      DG activity may contribute to amnesic symptoms in aMCI patients and aged adults.

PMID- 29031809
TI  - Grouping subjects based on conditioning criteria reveals differences in
      acquisition rates and in strength of conditioning-specific reflex modification.
AB  - Averaging behavioral data such as the nictitating membrane response (NMR) across
      subjects can conceal important individual and group differences. Analyses were
      conducted of NMR data from rabbits that were grouped based on the point during
      NMR conditioning when subjects produced 8 conditioned responses (CR) in a set of
      10 trials. This resulted in five groups (Early Day 1, Late Day 1, Early Day 2,
      Late Day 2, Early Day 3) in which group differences in CR acquisition rates were
      found. Percent (%) CRs were not found to increase monotonically and between
      session differences in % CR were found. Conditioning-specific reflex modification
      (CRM) of the NMR is a type of enhanced reflexive responding of the NMR that is
      detected when the unconditioned stimulus (US) is presented in the absence of the
      conditioned stimulus (CS) following paired classical conditioning. CRM occurred
      in some subjects in all five groups. Subjects from both the group that was
      fastest and the group that was slowest to reach the learning criterion had
      unconditioned response (UR) topographies following NMR conditioning that strongly
      resembled the CR-UR response sequence elicited during NMR conditioning. This
      finding was most pronounced when the US duration used to assess CRM was
      equivalent to that used during NMR conditioning, further evidence to support the
      hypothesis that CRM is a CR that has generalized from the CS to the US. While
      grouping data based on conditioning criteria did not facilitate identifying
      individuals more predisposed to exhibiting CRM, strong CRM only occurred in the
      groups that reached the conditioning criterion the fastest.

PMID- 29031810
TI  - The role of three-dimensional pseudo-continuous arterial spin labelling in
      grading and differentiating histological subgroups of meningiomas.
AB  - AIM: To evaluate the usefulness of pseudo-continuous arterial spin labelling
      (pCASL) imaging in grading and differentiating histological subtypes of
      meningiomas. MATERIALS AND METHODS: In this prospective study, conventional
      magnetic resonance imaging (MRI) with contrast-enhanced T1-weighted images and
      pCASL were acquired with a 3 T MRI system before surgery in 125 consecutive
      patients with suspected meningiomas. Finally, the perfusion parameters were
      collected from 84 grade I and 23 grade II meningiomas. On the pCASL perfusion
      map, the mean absolute cerebral blood flow (CBF) values from the meningioma
      (CBFtumour), peritumoural oedema (CBFPTO), white matter of contralateral centrum
      semi-ovale (CBFwm) and normal grey matter (CBFgm) were calculated. Additionally,
      the associations of these perfusion parameters with the value of ki-67 index were
      analysed. RESULTS: The CBFwm value correlated negatively with the largest
      diameter of the tumour, which limited its usage as a reference for ratio
      calculation. The CBFtumour values of grade II and grade I meningiomas did not
      differ significantly: 137.36+/-71.85 ml/min/100 g versus 123.58+/-135.80
      ml/min/100 g (p=0.641). The CBFPTO value was higher for grade II meningioma as
      than for grade I meningiomas: 30.30+/-15.56 ml/min/100 g versus 22.33+/-9.87
      ml/min/100 g (p=0.037). The CBFtumour value was highest in angiomatous meningioma
      and lowest in fibrous meningioma, thus enabling the differentiation of subtypes
      of meningioma. The CBFtumour value did not correlate with the ki-67 index of
      meningioma. CONCLUSION: The CBFPTO value, rather than the CBFtumour value, from
      pCASL imaging may serve as a key factor in distinguishing different grades of
      meningiomas. Moreover, angiomatous meningiomas and fibrous meningiomas can be
      identified by CBFtumour value.

PMID- 29031811
TI  - Production of low molecular collagen peptides-loaded liposomes using different
      charged lipids.
AB  - To encapsulate water soluble collagen peptides, liposomes loaded with peptides
      were assembled using a combination of thin film hydration and ultrasonication
      emulsification techniques. The influence of lipid charge, duration and power of
      ultrasonication, and collagen peptide concentration were evaluated. Layered
      liposomes loaded with collagen peptides, charged lipids, chitosan (+) or low
      methoxyl pectin (-) were produced using the layer-by-layer electrostatic
      deposition method. For the liposomes loaded with collagen peptides, the most
      efficient and dependable manufacturing method was variation of the
      ultrasonication duration, which was capable of producing smaller sizes (through
      increasing ultrasonication duration) and liposomes loaded with peptides with >60%
      encapsulation efficiency. For layered liposomes loaded with collagen peptides,
      charged lipids were determined to be more effective in the production of smaller
      liposomes than charged biopolymers. In addition, layered and non-layered
      liposomes loaded with peptides with a particle size <100nm were physically stable
      during storage, regardless of storage temperature and time.

PMID- 29031812
TI  - Nestmate discrimination based on familiarity but not relatedness in eastern
      carpenter bees.
AB  - How animals recognize conspecific individuals has important outcomes in many
      contexts, but interactions among group members are particularly important. Two
      recognition criteria are often implicated in these interactions: kin recognition
      is based on relatedness cues and nestmate recognition is based on familiarity.
      For social insects, both types of recognition are possible, as many nestmates are
      close kin and familiarity can develop among individuals that encounter each other
      repeatedly. To discern whether social insects use kin or nestmate recognition, it
      is necessary to simultaneously assess how relatedness and familiarity influence
      behaviour. The facultatively social eastern carpenter bee, Xylocopa virginica,
      offers an excellent opportunity to study how either nestmate or kin recognition
      (or both) may influence interactions among nestmates, as many females disperse
      from their natal nests in spring, and often attempt to join new colonies that may
      contain unrelated individuals. This leads to frequent behavioural interactions
      among females that may be related or unrelated, and familiar or unfamiliar. We
      used observation nests and microsatellite loci to assess the influence of
      familiarity and relatedness on behavioural interactions during the early phase of
      colony development, when females establish reproductive queues prior to brood
      production. Females were more likely to feed and were less aggressive to familiar
      rather than related nestmates, regardless of their relatedness. This suggests
      that eastern carpenter bees primarily use learned cues to discriminate among
      nestmates. Interactions with nestmates were also context-dependent, as females
      returning to the nest without food were the recipients of more aggression than
      those returning with food. If spring dispersal leads to reduced relatedness in X.
      virginica colonies, then nestmate recognition based on familiarity would be an
      important factor in maintaining group cohesion.

PMID- 29031814
TI  - Condom use in adolescents and young women following initiation of long- or short
      acting contraceptive methods.
AB  - OBJECTIVE: The objective was to determine if young women initiating long-acting
      reversible contraceptives (LARCs) who report new sexual partner(s) would be less
      likely to report use of a condom than women using short-acting reversible
      contraceptive (SARC) methods. STUDY DESIGN: We enrolled a prospective cohort of
      13-24-year-old women attending an adolescent-specific contraception clinic.
      Participants completed questionnaires at the contraceptive initiation visit and 6
      months later. At follow-up, we asked if they had sexual intercourse with a new
      partner, if they had used condoms, if their condom use patterns had changed and
      why. We analyzed factors associated with condom use. RESULTS: We enrolled 1048
      women; 771 (73.6%) initiated LARC and 384 (36.6%) initiated SARC. At 6 months,
      508 participants (48.5%) completed the follow-up survey: 380 LARC initiators and
      128 SARC initiators. Approximately 23% of LARC initiators and 27% of SARC
      initiators reported a new partner. SARC initiators who had a new partner were
      more likely to report condom use at least one time than LARC initiators reporting
      a new partner [82.4% vs. 59.6%; odds ratio (OR): 3.17, 95% confidence interval
      (CI): 1.19-8.43]. Such condom use was 42% higher among LARC initiators who
      reported a new sexual partner than those without and 38% higher for SARC
      initiators. In multivariable logistic regression, new sexual partner [adjusted OR
      (aOR) 3.29, 95% CI 2.10-5.16], SARC initiation (aOR 2.08, 95% CI 1.35-3.22) and
      age <20 (aOR 1.68, 95% CI 1.14-2.49) were independent predictors of condom use.
      CONCLUSION: While young women are less likely to report condom use in the 6
      months after initiating a LARC than after initiating a short-acting method, both
      groups increase their condom use similarly if they report a new sexual partner.
      IMPLICATIONS: The differential in condom use between LARC initiators and SARC
      initiators is likely related to their perceived need for pregnancy prevention, as
      both groups increase their condom use similarly if they had new sexual partners.

PMID- 29031813
TI  - Song practice as a rewarding form of play in songbirds.
AB  - In adult songbirds, the primary functions of song are mate attraction and
      territory defense; yet, many songbirds sing at high rates as juveniles and
      outside these primary contexts as adults. Singing outside primary contexts is
      critical for song learning and maintenance, and ultimately necessary for breeding
      success. However, this type of singing (i.e., song "practice") occurs even in the
      absence of immediate or obvious extrinsic reinforcement; that is, it does not
      attract mates or repel competitors. Here we review studies that support the
      hypothesis that song practice is stimulated and maintained by intrinsic reward
      mechanisms (i.e., that it is associated with a positive affective state).
      Additionally, we propose that song practice can be considered a rewarding form of
      play behavior similar to forms of play observed in multiple young animals as they
      practice sequences of motor events that are used later in primary adult
      reproductive contexts. This review highlights research suggesting at least
      partially overlapping roles for neural reward systems in birdsong and mammalian
      play and evidence that steroid hormones modify these systems to shift animals
      from periods of intrinsically rewarded motor exploration (i.e., singing in birds
      and play in mammals) to the use of similar motor patterns in primary reproductive
      contexts.

PMID- 29031815
TI  - Uptake and correlates of contraception among postpartum women in Kenya: results
      from a national cross-sectional survey.
AB  - OBJECTIVE: The objective was to characterize uptake and correlates of effective
      contraceptive use postpartum. STUDY DESIGN: We analyzed data from a national,
      cross-sectional evaluation of prevention of mother-to-child HIV transmission
      programs that enrolled women attending 6-week or 9-month infant immunization
      visits at 120 Kenyan maternal and child health clinics. We classified women who
      resumed sexual activity postpartum and did not desire a child within 2 years as
      having a need for family planning (FP). RESULTS: We included 955 (94%) of 1012
      women 8-10 months postpartum in the analysis. Mean age was 25.8 years and 36%
      were primigravidas. By 9 months postpartum, 62% of all women used contraception
      and 59% used effective contraception [injectables, implants, intrauterine devices
      [IUDs], oral contraceptives [OCs] and tubal ligations]. Most contraceptive users
      (61%) used injectables, followed by implants (10%), OCs (6%), IUDs (4%) and
      condoms alone (2%). The majority (n=733, 77%) had a need for FP, and 67% of 733
      women with FP need used effective contraception. Among women with a need for FP,
      effective contraception use was higher among those who discussed FP in postnatal
      care (PNC) than who did not discuss FP in PNC [prevalence ratio (PR) for PNC
      alone: 1.35, 95% confidence interval (CI): 1.16-1.58; PR for PNC and antenatal
      care (ANC): 1.42, 95% CI: 1.21-1.67; p=.001 for both]. CONCLUSIONS: Two thirds of
      postpartum women with a need for FP used effective contraception at 9 months
      postpartum, and use was associated with discussing FP during PNC. IMPLICATIONS:
      Integrating FP counseling in ANC/PNC could be an effective strategy to increase
      effective contraception use.

PMID- 29031816
TI  - Designing immunostimulatory double stranded messenger RNA with maintained
      translational activity through hybridization with poly A sequences for effective
      vaccination.
AB  - Messenger (m)RNA vaccines require a safe and potent immunostimulatory adjuvant.
      In this study, we introduced immunostimulatory properties directly into mRNA
      molecules by hybridizing them with complementary RNA to create highly immunogenic
      double stranded (ds)RNAs. These dsRNA formulations, comprised entirely of RNA,
      are expected to be safe and highly efficient due to antigen expression and
      immunostimulation occurring simultaneously in the same antigen presenting cells.
      In this strategy, design of dsRNA is important. Indeed, hybridization using full
      length antisense (as)RNA drastically reduced translational efficiency. In
      contrast, by limiting the hybridized portion to the mRNA poly A region, efficient
      translation and intense immunostimulation was simultaneously obtained. The immune
      response to the poly U-hybridized mRNAs (mRNA:pU) was mediated through Toll-like
      receptor (TLR)-3 and retinoic acid-inducible gene (RIG)-I. We also demonstrated
      that mRNA:pU activation of mouse and human dendritic cells was significantly more
      effective than activation using single stranded mRNA. In vivo mouse immunization
      experiments using ovalbumin showed that mRNA:pU significantly enhanced the
      intensity of specific cellular and humoral immune responses, compared to single
      stranded mRNA. Our novel mRNA:pU formulation can be delivered using a variety of
      mRNA carriers depending on the purpose and delivery route, providing a versatile
      platform for improving mRNA vaccine efficiency.

PMID- 29031817
TI  - BCRP/ABCG2 and high-alert medications: Biochemical, pharmacokinetic,
      pharmacogenetic, and clinical implications.
AB  - The human breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding
      cassette efflux transporter that uses ATP hydrolysis to expel xenobiotics from
      cells, including anti-cancer medications. It is expressed in the gastrointestinal
      tract, liver, kidney, and brain endothelium. Thus, ABCG2 functions as a tissue
      barrier to drug transport that strongly influences the pharmacokinetics of
      substrate medications. Genetic polymorphisms of ABCG2 are closely related to
      inter-individual variations in therapeutic performance. The common single
      nucleotide polymorphism c.421C>A, p.Q141K reduces cell surface expression of
      ABCG2 protein, resulting in lower efflux of substrates. Consequently, a higher
      plasma concentration of substrate is observed in patients carrying an ABCG2
      c.421C>A allele. Detailed pharmacokinetic analyses have revealed that altered
      intestinal absorption is responsible for the distinct pharmacokinetics of ABCG2
      substrates in genetic carriers of the ABCG2 c.421C>A polymorphism. Recent studies
      have focused on the high-alert medications among ABCG2 substrates (defined as
      those with high risk of adverse events), such as tyrosine kinase inhibitors
      (TKIs) and direct oral anti-coagulants (DOACs). For these high-alert medications,
      inter-individual variation may be closely related to the severity of side
      effects. In addition, ethnic differences in the frequency of ABCG2 c.421C>A have
      been reported, with markedly higher frequency in East Asian (~30-60%) than
      Caucasian and African-American populations (~5-10%). Therefore, ABCG2
      polymorphisms must be considered not only in the drug development phase, but also
      in clinical practice. In the present review, we provide an update of basic and
      clinical knowledge on genetic polymorphisms of ABCG2.

PMID- 29031819
TI  - Managing text-recycling: an ongoing issue.

PMID- 29031818
TI  - Camptothecin and its analog SN-38, the active metabolite of irinotecan, inhibit
      binding of the transcriptional regulator and oncoprotein FUBP1 to its DNA target
      sequence FUSE.
AB  - The transcriptional regulator FUSE Binding Protein 1 (FUBP1) is overexpressed in
      more than 80% of all human hepatocellular carcinomas (HCCs) and other solid tumor
      entities including prostate and colorectal carcinoma. FUBP1 expression is
      required for HCC tumor cell expansion, and it functions as an important pro
      proliferative and anti-apoptotic oncoprotein that binds to the single-stranded
      DNA sequence FUSE to regulate the transcription of a variety of target genes. In
      this study, we screened an FDA-approved drug library and discovered that the
      Topoisomerase I (TOP1) inhibitor camptothecin (CPT) and its derivative 7-ethyl-10
      hydroxycamptothecin (SN-38), the active irinotecan metabolite that is used in the
      clinics in combination with other chemotherapeutics to treat carcinoma, inhibit
      FUBP1 activity. Both molecules prevent in vitro the binding of FUBP1 to its
      single-stranded target DNA FUSE, and they induce deregulation of FUBP1 target
      genes in HCC cells. Our results suggest the interference with the FUBP1/FUSE
      interaction as a further molecular mechanism that, in addition to the
      inactivation of TOP1, may contribute to the therapeutic potential of CPT/SN-38.
      Targeting of FUBP1 in HCC therapy with SN-38/irinotecan could be a particularly
      interesting option because of the high FUBP1 levels in HCC cells and their
      dependency on FUBP1 expression.

PMID- 29031820
TI  - Suidae from Kanapoi.
AB  - The whole collection of Suidae from Kanapoi is revised in the context of the
      systematics and evolution of Nyanzachoerus in the Pliocene of Eastern Africa. It
      contains only two species, Nyanzachoerus kanamensis and Notochoerus jaegeri. The
      size and morphology of their premolars overlap, but not those of their m3s. No
      transitional form between them is known in Kenya, but some populations from
      Uganda and Ethiopia display intermediate characters, suggesting that No. jaegeri
      could be descended from a kanamensis-like ancestor. However, the cranial remains
      of No. jaegeri from Kanapoi are insufficient to formally establish the affinities
      of the species. On the basis of the dentition, Notochoerus euilus could be
      descended from No. jaegeri. The noticeable absence of Kolpochoerus at Kanapoi
      (and in the whole Turkana Basin at that time) remains unexplained. The presence
      of a species with affinity to Nyanzachoerus tulotos at Ekora raises the
      possibility that uppermost Miocene sediments occur there.

PMID- 29031821
TI  - Development of an antigen specific colloidal gold immunochromatographic assay for
      detection of antibody to M. wenyonii in bovine sera.
AB  - The goal of this research was to develop a colloidal gold immunochromatographic
      strip test for detection of antibody to Mycoplasma wenyonii (M. wenyonii) in
      bovine using specific antigen. M. wenyonii was isolated from blood samples from
      the spontaneously infected cattle in Hebei province, China. Suspensions of the M.
      wenyonii antigenic proteins were prepared by freeze-thaw cycles and
      ultrasonication. Candidate antigens were screened with sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. The specific
      bands of the most antigenic proteins were excised from the gel and were purified
      by using a gel extraction kit. A colloidal gold immunochromatographic assay using
      the purified specific proteins as the coating antigen (sp-GICA) was developed for
      detection of antibody to M. wenyonii. Blood samples from cows in the field were
      tested for antibody to M. wenyonii by the sp-GICA strip and enzyme-linked
      immunosorbent assay (ELISA) simultaneously to compare the specificity,
      sensitivity and accuracy. The results showed that the specific proteins bands
      with sufficient immunoreactivity have been identified. The apparent molecular
      weights of the proteins were 115 kDa and 60 kDa, respectively. The stability and
      reproducibility were quite excellent after the storage of the strip at room
      temperature for 5 months. This sp-GICA showed 95.48% (148/155), 92.86% (39/42)
      and 94.92% (187/197) in terms of specificity, sensitivity and accuracy compared
      to ELISA. The sp-GICA described here shows excellent agreement with ELISA and it
      is shown to be a simple, convenient, specific and highly sensitive assay for
      detection of serum antibodies to M. wenyonii.

PMID- 29031822
TI  - A systematic review of volar locking plate removal after distal radius fracture.
AB  - BACKGROUND: Indication of volar locking plate (VLP) removal after bony healing of
      distal radius fracture (DRF) is controversial. Studies with various range of
      removal rate were reported. The purpose of this systematic review was to
      investigate the frequency and the reasons of hardware removal over the world. We
      hypothesized that more frequent VLP removal contribute to better clinical
      outcomes. METHODS: The authors searched all available literature in the PubMed
      and EMBASE databases for articles reporting on outcomes of treatment using VLP
      for DRF. Data collection included hardware removal rate, complication rate,
      clinical and radiological outcomes. We analyzed correlation between hardware
      removal rate with clinical and radiological outcomes. RESULTS: A total of 3472
      articles were screened, yielding 52 studies for final review. The mean hardware
      removal rate was 9%, ranging from 0 to 100%. The mean removal rate in studies
      from France, Norway, Japan, and Belgium was as high as 19%. The mean removal rate
      in studies from the US was low (3%). The most frequent reasons for extraction
      were routine removal (22%), tendon irritation or tenosynovitis (14%), hardware
      problem (14%), and patient' request (13%). Although routine removal and patient'
      request were not counted as complication, correlation between removal rate with
      complication rate was strong (rho=0.64, p<0.001). Correlations between clinical
      and radiological outcomes were week except for volar tilt (rho=-0.42, p=0.009).
      CONCLUSIONS: There was a diversity of removal rate and reasons in the studies
      over the world. High frequent VLP removal did not contribute to better clinical
      outcomes.

PMID- 29031823
TI  - Letter to the editor concerning "Is weather related to the number of assaults
      seen at emergency departments?"

PMID- 29031824
TI  - The Exeter Trauma Stem: A radiographic follow-up at minimum of five years post
      implantation.
AB  - INTRODUCTION: The Exeter Trauma Stem (ETS) has been recommended by National
      Institute of Clinical Excellence (NICE) guidelines in the United Kingdom as a
      proven, cemented stem. A single laboratory study in the literature has raised
      possible concerns about the polished finish of the ETS and subsequent potential
      for accelerated loosening although there is little clinical evidence to support
      or refute this. METHODS: The aim of this study was to assess clinical outcomes of
      the ETS at a minimum of five years post implantation. Primary outcomes were
      radiological loosening at a minimum of five years along with survivorship of the
      implant. Patient demographics were prospectively collected and followed up.
      RESULTS: 218 ETS's (in 214 patients) were implanted from June 2002 until August
      2008 in a single centre by a wide variety of surgeons of differing grades. Of
      these, 16 underwent revision surgery for fracture (2), dislocation (3), infection
      (1) and acetabular erosion (10) but there were no revisions for aseptic loosening
      of the implant. There were 64.0% (137/214) patients that had died by the time of
      this study. Of the remaining patients, 90 had radiographs of their hips at a
      minimum of 5 years with 36 of these at a minimum of 7 years post implantation.
      None of these had evidence of loosening. CONCLUSION: The ETS is a robust and
      suitable stem for implantation in patients with hip fractures. There are no
      clinical suspicions or increased rates of loosening with the ETS in our study.
      The concerns about surface finish are not borne out in our clinical study which
      shows no evidence of loosening at a minimum of five years post operation. It
      confers many advantages including ease of revision and it should continue to be
      used as per NICE guidelines.

PMID- 29031825
TI  - Hip fracture presentations are less frequent at weekends.

PMID- 29031826
TI  - The top 100 cited of injury-international journal of the care of the injured: A
      bibliometric analysis.
AB  - BACKGROUND: With nearly 50 years' of development, Injury has become one of the
      leading journals in its specialty. The aim of this article is to identify,
      analyze the characteristics of the 100 most cited articles published by the
      journal to date. METHOD: We searched the Thomson Reuters Web of Science Core
      Collection for citations of all articles published in Injury since its launch.
      For the Top 100 most frequently cited articles, title, author name, number of
      authors, publishing date, citation number, country of origin, institution, pages,
      number of reference, type of article, study topic, study design, funding source,
      and level of evidence of each clinical article were recorded and analyzed.
      RESULTS: Only 50 self-citations were found in 12436 total citations of the top100
      articles, fifty-four articles exceeded 100 citations. Total citations of the Top
      100 articles ranged from 77 to 599. The Top 100 articles were published between
      1973 and 2012, the mean authorship and institution number per paper was 3.92 and
      1.84 respectively. The mean page number was 8.26 and the mean reference number
      was 45.2. England, Germany and Switzerland ranked the top three countries of
      origin. Among the T100 articles, there were 50 clinical studies, 5 basic
      researches, and 45 reviews. The most common study type was case series, and most
      common topics were bone reconstruction, trauma and bone fracture. The most common
      level of evidence was level IV. CONCLUSIONS: This study may help researchers to
      find out the important information on the classic articles and provides useful
      insights for the authors who want to publish their research in Injury.

PMID- 29031827
TI  - Development of a surgical site infection prediction model in orthopaedic trauma:
      The Denver Health Model.
AB  - BACKGROUND: The CDC's National Healthcare Safety Network's (NHSN) current risk
      adjustment model for surgical site infections (SSI) following open reduction
      internal fixation (ORIF) of long bone fractures is a suboptimal predictor of
      risk. We hypothesized that by including variables known to be associated with SSI
      following ORIF, we would develop a model that would increase the accuracy and
      predictability of SSI risk. METHODS: Patients who underwent ORIF of a long bone
      between January 1, 2012 and December 31, 2014 were included in the study
      (n=1543). Patient risk factors, injury risk factors and perioperative risk
      factors were considered in the development of this model. We developed a risk
      prediction model for SSI following ORIF and then applied this to a new dataset of
      ORIF to determine the expected number of infections. This was compared to the
      expected number of infections calculated using the NHSN risk adjusted model.
      RESULTS: The final multivariate model included age (odds ratio: 1.02, p
      value<0.001, 95% confidence interval: 1.00-1.04), lower leg fracture (2.63,
      0.004, 1.40-4.93), open fracture (1.87, 0.07, 0.93-3.76), American Society of
      Anesthesiologists (ASA) (2.09, 0.02, 1.07-4.08) and history of methicillin
      resistant Staphylococcus aureus (MRSA), which was the most important predictor of
      infection (7.20, <0.001, 2.61-19.85). The c-index was 0.74 compared to 0.65 for
      the NHSN model, indicating that our model more accurate in estimating infection
      risk. When the developed model was used to predict the number of expected
      infections on a new dataset from 2015, 36.3 SSI were expected compared to 5.7
      calculated by the NHSN model. CONCLUSIONS: The model that was developed uses five
      easily identifiable risk factors that result in a more accurate prediction of
      infection at our facility than the currently used model. LEVEL OF EVIDENCE:
      Prognostic and epidemiologic study, level III.

PMID- 29031828
TI  - Non-progressing cancer patients have persistent B cell responses expressing
      shared antibody paratopes that target public tumor antigens.
AB  - There is significant debate regarding whether B cells and their antibodies
      contribute to effective anti-cancer immune responses. Here we show that patients
      with metastatic but non-progressing melanoma, lung adenocarcinoma, or renal cell
      carcinoma exhibited increased levels of blood plasmablasts. We used a cell
      barcoding technology to sequence their plasmablast antibody repertoires,
      revealing clonal families of affinity matured B cells that exhibit progressive
      class switching and persistence over time. Anti-CTLA4 and other treatments were
      associated with further increases in somatic hypermutation and clonal family
      size. Recombinant antibodies from clonal families bound non-autologous tumor
      tissue and cell lines, and families possessing immunoglobulin paratope sequence
      motifs shared across patients exhibited increased rates of binding. We identified
      antibodies that caused regression of, and durable immunity toward, heterologous
      syngeneic tumors in mice. Our findings demonstrate convergent functional anti
      tumor antibody responses targeting public tumor antigens, and provide an approach
      to identify antibodies with diagnostic or therapeutic utility.

PMID- 29031829
TI  - Gain-of-function variants in NLRP1 protect against the development of diabetic
      kidney disease: NLRP1 inflammasome role in metabolic stress sensing?
AB  - Although inflammasome plays a well-known role in animal models of renal injury,
      limited studies in humans are available, and its participation in diabetic kidney
      disease (DKD) remains unknown. Aim of this study was to elucidate the
      contribution of inflammasome genetics in the development of DKD in type-1
      diabetes (T1D). The association of functional variants in inflammasome genes with
      DKD was assessed by multivariate analysis in a retrospective and in a prospective
      cohort. NLRP1 rs2670660 and rs11651270 polymorphisms were significantly
      associated with a decrease risk to develop DKD (padj<0.01), and rs11651270 also
      with a lower risk of new renal events during follow-up (padj=0.01). Supporting
      these findings, diabetes metabolites (glycated albumin and high glucose) were
      able to modulate NLRP1 expression. This study is the first to suggest a
      protective role of NLRP1 in DKD, highlighting an emerging role of NLRP1 as a
      homeostatic factor against metabolic stress.

PMID- 29031830
TI  - Action observation facilitates motor cortical activity in patients with stroke
      and hemiplegia.
AB  - Motor imagery (MI) is a mental practice that reproduces the visual- and/or
      kinesthetic-modality brain activations accompanying movement. It is a useful
      rehabilitation technique as the affected motor cortex can be stimulated in
      patients with stroke and hemiplegia. However, most patients with stroke have
      difficulty with MI owing to advanced age and/or higher-cognitive dysfunction,
      thus impairing their ability to internally simulate the action. We therefore
      investigated whether action observation (AO), an alternative form of motor
      stimulation that works via the mirror-neuron system, could facilitate motor
      cortical activity in such patients. Combined AO and physical training of the
      observed actions has been reported to have a positive impact on motor deficits
      after stroke. Eleven patients with stroke and hemiplegia affecting the hand
      performed MI and AO with verbal and video instructions under 19 channels of
      electroencephalogram (EEG) recording. The event-related desynchronization (ERD)
      was measured as an electroencephalographic marker of motor cortical activity. The
      ERD power in the AO condition (30.0+/-5.0%) was significantly higher than that in
      the MI condition (12.2+/-3.9%). These results suggest that AO could be a good
      option for patients with stroke who have difficulty using MI to effectively
      stimulate and reestablish cortical-peripheral motor pathways.

PMID- 29031831
TI  - Large-scale retrieval for medical image analytics: A comprehensive review.
AB  - Over the past decades, medical image analytics was greatly facilitated by the
      explosion of digital imaging techniques, where huge amounts of medical images
      were produced with ever-increasing quality and diversity. However, conventional
      methods for analyzing medical images have achieved limited success, as they are
      not capable to tackle the huge amount of image data. In this paper, we review
      state-of-the-art approaches for large-scale medical image analysis, which are
      mainly based on recent advances in computer vision, machine learning and
      information retrieval. Specifically, we first present the general pipeline of
      large-scale retrieval, summarize the challenges/opportunities of medical image
      analytics on a large-scale. Then, we provide a comprehensive review of algorithms
      and techniques relevant to major processes in the pipeline, including feature
      representation, feature indexing, searching, etc. On the basis of existing work,
      we introduce the evaluation protocols and multiple applications of large-scale
      medical image retrieval, with a variety of exploratory and diagnostic scenarios.
      Finally, we discuss future directions of large-scale retrieval, which can further
      improve the performance of medical image analysis.

PMID- 29031832
TI  - Initial brain aging: heterogeneity of mitochondrial size is associated with
      decline in complex I-linked respiration in cortex and hippocampus.
AB  - Brain aging is accompanied by declining mitochondrial respiration. We
      hypothesized that mitochondrial morphology and dynamics would reflect this
      decline. Using hippocampus and frontal cortex of a segmental progeroid mouse
      model lacking Cockayne syndrome protein B (CSBm/m) and C57Bl/6 (WT) controls and
      comparing young (2-5 months) to middle-aged mice (13-14 months), we found that
      complex I-linked state 3 respiration (CI) was reduced at middle age in CSBm/m
      hippocampus, but not in CSBm/m cortex or WT brain. In hippocampus of both
      genotypes, mitochondrial size heterogeneity increased with age. Notably, an
      inverse correlation between heterogeneity and CI was found in both genotypes,
      indicating that heterogeneity reflects mitochondrial dysfunction. The ratio
      between fission and fusion gene expression reflected age-related alterations in
      mitochondrial morphology but not heterogeneity. Mitochondrial DNA content was
      lower, and hypoxia-induced factor 1alpha mRNA was greater at both ages in CSBm/m
      compared to WT brain. Our findings show that decreased CI and increased
      mitochondrial size heterogeneity are highly associated and point to declining
      mitochondrial quality control as an initial event in brain aging.

PMID- 29031833
TI  - Structure-based drug design for envelope protein E2 uncovers a new class of
      bovine viral diarrhea inhibitors that block virus entry.
AB  - Antiviral targeting of virus envelope proteins is an effective strategy for
      therapeutic intervention of viral infections. Here, we took a computer-guided
      approach with the aim of identifying new antivirals against the envelope protein
      E2 of bovine viral diarrhea virus (BVDV). BVDV is an enveloped virus with an RNA
      genome responsible for major economic losses of the cattle industry worldwide.
      Based on the crystal structure of the envelope protein E2, we defined a binding
      site at the interface of the two most distal domains from the virus membrane and
      pursued a hierarchical docking-based virtual screening search to identify small
      molecule ligands of E2. Phenyl thiophene carboxamide derivative 12 (PTC12)
      emerged as a specific inhibitor of BVDV replication from in vitro antiviral
      activity screening of candidate molecules, displaying an IC50 of 0.30 MUM against
      the reference NADL strain of the virus. Using reverse genetics we constructed a
      recombinant BVDV expressing GFP that served as a sensitive reporter for the study
      of the mechanism of action of antiviral compounds. Time of drug addition assays
      showed that PTC12 inhibited an early step of infection. The mechanism of action
      was further dissected to find that the compound specifically acted at the
      internalization step of virus entry. Interestingly, we demonstrated that similar
      to PTC12, the benzimidazole derivative 03 (BI03) selected in the virtual screen
      also inhibited internalization of BVDV. Furthermore, docking analysis of PTC12
      and BI03 into the binding site revealed common interactions with amino acid
      residues in E2 suggesting that both compounds could share the same molecular
      target. In conclusion, starting from a targeted design strategy of antivirals
      against E2 we identified PTC12 as a potent inhibitor of BVDV entry. The compound
      can be valuable in the design of antiviral strategies in combination with already
      well-characterized polymerase inhibitors of BVDV.

PMID- 29031835
TI  - Metabolomic analysis of oxidative stress: Superoxide dismutase mutation and
      paraquat induced stress in Drosophila melanogaster.
AB  - Oxidative stress results in substantial biochemical and physiological
      perturbations in essentially all organisms. To determine the broad metabolic
      effects of oxidative stress, we have quantified the response in Drosophila
      melanogaster to both genetically and environmentally derived oxidative stress.
      Flies were challenged with loss of Superoxide dismutase activity or chronic or
      acute exposure to the oxidizing chemical paraquat. Metabolic changes were then
      quantified using a recently developed chemical isotope labeling (CIL) liquid
      chromatography - mass spectrometry (LC-MS) platform that targets the carboxylic
      acid and amine/phenol submetabolomes with high metabolic coverage. We discovered
      wide spread changes in both submetabolomes in response to all three types of
      stresses including: changes to the urea cycle, tryptophan metabolism, porphyrin
      metabolism, as well as a series of metabolic pathways involved in glutathione
      synthesis. Strikingly, while there are commonalities across the conditions, all
      three resulted in different metabolomic responses, with the greatest difference
      between the genetic and environmental responses. Genetic oxidative stress
      resulted in substantially more widespread effects, both in terms of the percent
      of the metabolome altered, and the magnitude of changes in individual
      metabolites. Chronic and acute environmental stress resulted in more similar
      responses although both were distinct from genetic stress. Overall, these results
      indicate that the metabolomic response to oxidative stress is complex, reaching
      across multiple metabolic pathways, with some shared features but with more
      features unique to different, specific stressors.

PMID- 29031836
TI  - Optofluidic time-stretch quantitative phase microscopy.
AB  - Innovations in optical microscopy have opened new windows onto scientific
      research, industrial quality control, and medical practice over the last few
      decades. One of such innovations is optofluidic time-stretch quantitative phase
      microscopy - an emerging method for high-throughput quantitative phase imaging
      that builds on the interference between temporally stretched signal and reference
      pulses by using dispersive properties of light in both spatial and temporal
      domains in an interferometric configuration on a microfluidic platform. It
      achieves the continuous acquisition of both intensity and phase images with a
      high throughput of more than 10,000 particles or cells per second by overcoming
      speed limitations that exist in conventional quantitative phase imaging methods.
      Applications enabled by such capabilities are versatile and include
      characterization of cancer cells and microalgal cultures. In this paper, we
      review the principles and applications of optofluidic time-stretch quantitative
      phase microscopy and discuss its future perspective.

PMID- 29031834
TI  - Dysregulation of neurotrophin signaling in the pathogenesis of Alzheimer disease
      and of Alzheimer disease in Down syndrome.
AB  - Neurotrophic factors, including the members of the neurotrophin family, play
      important roles in the development and maintenance of the nervous system. Trophic
      factor signals must be transmitted over long distances from axons and dendrites
      to the cell bodies of neurons. A mode of signaling well suited to the challenge
      of robust long distance signaling is the signaling endosome. We review the
      biology of signaling endosomes and the "signaling endosome hypothesis". Evidence
      for disruption of signaling endosome function in disorders of the nervous system
      is also reviewed. Changes in endosome structure in Alzheimer disease (AD) and
      Down syndrome (DS) are present early in these disorders. Data for the APP
      products responsible are reviewed and the consequent changes in signaling from
      endosomes discussed. We conclude by pointing to the need for additional studies
      to explore the biology of signaling endosomes in normal neurons and to elucidate
      their role in the pathogenesis of neurodegeneration.

PMID- 29031837
TI  - Impaired contrast sensitivity at low spatial frequency in cannabis users with
      early onset.
AB  - The regular use of cannabis generates pronounced cognitive disorders, especially
      in users who begin before the age of 15-16. However, less is known about the
      impact of regular cannabis on visual function, especially in the case of early
      onset. Cannabinoid receptors (CB1) are expressed in areas of the visual system,
      like the thalamus and primary cortex, which might originate sensory disorders.
      Hence, we measured contrast sensitivity (CS) in three groups, i.e. cannabis users
      with late onset of cannabis use (after 16 years old), cannabis users with early
      onset". We used a constant method which allowed us to control for biased
      responses. Stimuli were presented at high and low spatial frequencies and in both
      static and dynamic conditions (8Hz). As contrast sensitivity is measured
      behaviorally based on an explicit response and could thus be impacted by
      attentional or vigilance disorders, participants' attention and vigilance were
      carefully monitored by means of the D2 test, CPT-AX for attention and
      pupillography for vigilance. Cannabis users with early onset were significantly
      impaired only at low spatial frequency. This effect was independent of response
      bias, vigilance and attention. These results show for the first time that early
      cannabis use impacts contrast sensitivity at low spatial frequency.

PMID- 29031838
TI  - Does Attorney Advertising Influence Patient Perceptions of Pelvic Mesh?
AB  - OBJECTIVE: To measure the relative influence of attorney advertising on patient
      perceptions of pelvic mesh compared with a history of surgery and a first urology
      visit. MATERIALS AND METHODS: A 52-item survey was administered to 170 female
      patients in 2 urology offices between 2014 and 2016. Multiple survey items were
      combined to form scales for benefit and risk perceptions of pelvic mesh,
      perceptions of the advertising, attitudes toward pelvic mesh, and knowledge of
      pelvic mesh and underlying medical conditions. Data were analyzed using
      hierarchical linear regression models. RESULTS: Exposure to attorney advertising
      was quite high; 88% reported seeing a mesh-related attorney advertisement in the
      last 6 months. Over half of patients reported seeing attorney advertisements more
      than once per week. A history of prior mesh implant surgery was the strongest
      predictor of benefit and risk perceptions of pelvic mesh. Exposure to attorney
      advertising was associated with higher risk perceptions but did not significantly
      affect perceptions of benefits. Past urologist visits increased perceptions of
      benefits but had no effect on risk perceptions. CONCLUSION: Attorney advertising
      appears to have some influence on risk perceptions, but personal experience and
      discussions with a urogynecologist or urologist also influence patient
      perceptions. Implications, limitations, and future research are discussed.

PMID- 29031839
TI  - Utilization of Postpenile Surgery Illustrated Healing Atlas: A Comparative Study.
AB  - OBJECTIVE: To determine the effect of the postpenile surgery illustrated healing
      atlas on caregivers' anxiety levels pre- and postoperatively, the frequency of
      family's postoperative communication with the urology care team, and the number
      of unplanned emergency room (ER) return for wound checks. METHODS: A prospective
      cohort enrolled children who underwent penile surgeries (distal hypospadias
      repair and phalloplasty) with no concomitant procedures from December 2016 to
      June 2017. A 6-item short-form Spielberger State-Trait Anxiety Inventory (STAI)
      was used to determine baseline and postoperative anxiety levels of the
      caregivers. Two groups were created: caregivers who did not view the illustrated
      atlas vs caregivers who were shown the atlas. Baseline characteristics and
      demographics were compared, along with caregiver's pre- to postoperative anxiety
      level difference, frequency of postoperative communication, and number of
      unplanned ER return for wound checks. RESULTS: Fifty-four patients were enrolled
      with 27 families in each group. Baseline characteristics and demographics were
      comparable with no significant differences. The assessment of the pre- to
      postoperative anxiety levels in both groups showed no significant differences
      (median difference -5 [interquartile range -8 to -5] vs -5 [interquartile range 
      8 to -4], P = .94). Although no differences were noted for ER-return rates
      between the groups (18% vs 11.1%, P = .704), significantly less postoperative
      calls and e-mails were noted among families who received or viewed the postpenile
      surgery illustrated healing atlas (51.9% vs 11.1%, P = .003). CONCLUSION: The
      utilization of a postpenile surgery illustrated healing atlas as part of the
      postoperative support provided to families was able to decrease postoperative
      calls and e-mails.

PMID- 29031840
TI  - Urethral Reconstruction in Aging Male Patients.
AB  - OBJECTIVE: To report stricture characteristics, complications, and treatment
      outcomes among elderly men undergoing urethral reconstruction. MATERIALS AND
      METHODS: A retrospective review of urethroplasty cases and outcomes by a single
      surgeon from 2007 to 2014 was performed. Men were stratified by decade of life at
      time of surgery (<50, 50-59, 60-69, >=70 years). Individuals with a history of
      hypospadias were excluded. RESULTS: Among 514 urethroplasty procedures, 184 (36%)
      were evaluated in men >=60 years. When stratified by decade of life, elderly men
      were more likely to have a history of radiation therapy (0% vs 5% vs 19% vs 50%;
      P <.0001) and experience treatment failure (6% vs 16% vs 20% vs 26%; P <.0001)
      during follow-up (median 63 months). The estimated 60-month stricture recurrence
      free survival decreased with increasing age at time of urethroplasty (94% vs 89%
      vs 78% vs 74%; P <.0001). In patients >=60 years, success rates of anastomotic,
      substitution, and urethrostomy techniques were 80%, 65%, and 88%; anastomotic
      urethroplasty success improved after excluding those patients with prior
      radiation. After surgery, elderly were more likely to have voiding dysfunction
      and <90-day Clavien >=3 complications requiring endoscopic intervention. On
      multivariable analysis, advancing age per decade beyond 50 years was
      independently associated with risk of urethroplasty failure-50-59 (hazard ratio
      [HR] 2.39; P = .02), 60-69 (HR 2.80; P = .009), and >=70 (HR 3.43; P = .003).
      CONCLUSION: Urethroplasty is safe and effective in the majority of elderly men.
      Early reconstructive intervention with anastomotic urethroplasty or urethrostomy
      techniques may optimize outcomes. Voiding dysfunction and prostatic obstruction
      are common in this population and should be pursued as clinically indicated.

PMID- 29031841
TI  - Management of Postradical Prostatectomy Urinary Incontinence: A Review.
AB  - Postprostatectomy urinary incontinence has a significant impact on the quality of
      life of patients who undergo radical prostatectomy. Stress and overflow
      incontinence may result from the procedure, with sphincteric incompetence and
      detrusor hypocontractility implicating their development, respectively. In many
      cases, treatment begins with conservative approaches, including pelvic floor
      muscle training or biofeedback. Pharmacotherapy can be used to treat overactive
      bladder. For stress incontinence, transurethral bulking agents are utilized in
      select patients; however, artificial urinary sphincter and male slings are the
      most efficacious options with good success rates. In this review, the various
      treatment modalities are critically discussed with special emphasis on safety and
      efficacy.

PMID- 29031842
TI  - Ribosome Profiling Reveals Genome-wide Cellular Translational Regulation upon
      Heat Stress in Escherichia coli.
AB  - Heat shock response is a classical stress-induced regulatory system in bacteria,
      characterized by extensive transcriptional reprogramming. To compare the impact
      of heat stress on the transcriptome and translatome in Escherichia coli, we
      conducted ribosome profiling in parallel with RNA-Seq to investigate the
      alterations in transcription and translation efficiency when E. coli cells were
      exposed to a mild heat stress (from 30  degrees C to 45  degrees C). While
      general changes in ribosome footprints correlate with the changes of mRNA
      transcripts upon heat stress, a number of genes show differential changes at the
      transcription and translation levels. Translation efficiency of a few genes that
      are related to environment stimulus response is up-regulated, and in contrast,
      some genes functioning in mRNA translation and amino acid biosynthesis are down
      regulated at the translation level in response to heat stress. Moreover, our
      ribosome occupancy data suggest that in general ribosomes accumulate remarkably
      in the starting regions of ORFs upon heat stress. This study provides additional
      insights into bacterial gene expression in response to heat stress, and suggests
      the presence of stress-induced but yet-to-be characterized cellular regulatory
      mechanisms of gene expression at translation level.

PMID- 29031845
TI  - Tackling viral haemorrhagic fever in Africa.

PMID- 29031843
TI  - RNA Regulations and Functions Decoded by Transcriptome-wide RNA Structure
      Probing.
AB  - RNA folds into intricate structures that are crucial for its functions and
      regulations. To date, a multitude of approaches for probing structures of the
      whole transcriptome, i.e., RNA structuromes, have been developed. Applications of
      these approaches to different cell lines and tissues have generated a rich
      resource for the study of RNA structure-function relationships at a systems
      biology level. In this review, we first introduce the designs of these methods
      and their applications to study different RNA structuromes. We emphasize their
      technological differences especially their unique advantages and caveats. We then
      summarize the structural insights in RNA functions and regulations obtained from
      the studies of RNA structuromes. And finally, we propose potential directions for
      future improvements and studies.

PMID- 29031846
TI  - Xanthoma disseminatum.

PMID- 29031844
TI  - Alternative Polyadenylation: Methods, Findings, and Impacts.
AB  - Alternative polyadenylation (APA), a phenomenon that RNA molecules with different
      3' ends originate from distinct polyadenylation sites of a single gene, is
      emerging as a mechanism widely used to regulate gene expression. In the present
      review, we first summarized various methods prevalently adopted in APA study,
      mainly focused on the next-generation sequencing (NGS)-based techniques specially
      designed for APA identification, the related bioinformatics methods, and the
      strategies for APA study in single cells. Then we summarized the main findings
      and advances so far based on these methods, including the preferences of
      alternative polyA (pA) site, the biological processes involved, and the
      corresponding consequences. We especially categorized the APA changes discovered
      so far and discussed their potential functions under given conditions, along with
      the possible underlying molecular mechanisms. With more in-depth studies on
      extensive samples, more signatures and functions of APA will be revealed, and its
      diverse roles will gradually heave in sight.

PMID- 29031847
TI  - Department of Error.

PMID- 29031849
TI  - Investigation of factors affecting the stability of lysozyme spray dried from
      ethanol-water solutions.
AB  - Formulation composition and processing conditions can be adjusted to enhance the
      structural integrity as well as the bioactivity of proteins in the spray drying
      process. In this study, lysozyme was chosen as a model pharmaceutical protein to
      study these aspects when spray drying from water-ethanol mixtures. The effect of
      formulation additives (trehalose, Tween 20 and phosphate-buffered saline) and
      processing conditions (inlet temperature and storage time of lysozyme in the feed
      solution before the spray drying process) on the protein bioactivity was
      investigated. The results showed that the bioactivities of spray dried lysozyme
      with these additives were about 5-10% higher than that without additives. The
      bioactivity of the spray dried lysozyme was found to increase with a decrease in
      the inlet temperature from 130 degrees C to 80 degrees C, with similar findings
      when shortening the storage time of the feed solutions prior to spray drying.
      Fourier Transform Infrared (FTIR) and Circular Dichroism (CD) results showed that
      the native structures of lysozyme were largely restored upon reconstitution of
      the spray dried powder in water after the spray drying process. This suggests
      that the bioactivity of lysozyme could be preserved adequately by optimization of
      both the formulation composition and process conditions even when spray drying
      from a water-ethanol mixture.

PMID- 29031850
TI  - Nucleic acid loading and fluorescent labeling of isolated extracellular vesicles
      requires adequate purification.
AB  - Extracellular vesicles (EVs) are nanosized vesicular structures released by cells
      to communicate with one another. The growing interest in the (patho)physiological
      function and potential pharmaceutical application of these vesicles is
      accompanied by a vast number of new research groups entering this research field
      and a plethora of different protocols to separate EVs from non-vesicular
      components. This lack of uniformity often generates conflicting or difficult-to
      compare results. Here we provide a comparative analysis of different EV isolation
      strategies, discussing the purity of the final isolate and highlighting the
      importance of purity on downstream experimental readouts. First, we show that
      ultracentrifugation (UC) of B16F10 melanoma cell-derived conditioned medium co
      purifies proteins or protein complexes with nuclease activity. Such contaminants
      should be taken into account when aiming to apply EVs as delivery carriers for
      exogenous nucleic acids. Second, three commonly used purification strategies
      (i.e. precipitation, UC and density-gradient centrifugation) were evaluated for
      their ability to remove non-incorporated fluorescent dye (i.e. the lipophilic
      PKH67 dye), important when probing EV interactions with cells. For both types of
      impurities, endogenous and exogenous, density gradient purification outperforms
      the other evaluated methods. Overall, these results demonstrate that the
      implementation of stringent purification protocols and adequate controls is of
      pivotal importance to draw reliable conclusions from downstream experiments
      performed with EV isolates.

PMID- 29031848
TI  - Local, national, and regional viral haemorrhagic fever pandemic potential in
      Africa: a multistage analysis.
AB  - BACKGROUND: Predicting when and where pathogens will emerge is difficult, yet, as
      shown by the recent Ebola and Zika epidemics, effective and timely responses are
      key. It is therefore crucial to transition from reactive to proactive responses
      for these pathogens. To better identify priorities for outbreak mitigation and
      prevention, we developed a cohesive framework combining disparate methods and
      data sources, and assessed subnational pandemic potential for four viral
      haemorrhagic fevers in Africa, Crimean-Congo haemorrhagic fever, Ebola virus
      disease, Lassa fever, and Marburg virus disease. METHODS: In this multistage
      analysis, we quantified three stages underlying the potential of widespread viral
      haemorrhagic fever epidemics. Environmental suitability maps were used to define
      stage 1, index-case potential, which assesses populations at risk of infection
      due to spillover from zoonotic hosts or vectors, identifying where index cases
      could present. Stage 2, outbreak potential, iterates upon an existing framework,
      the Index for Risk Management, to measure potential for secondary spread in
      people within specific communities. For stage 3, epidemic potential, we combined
      local and international scale connectivity assessments with stage 2 to evaluate
      possible spread of local outbreaks nationally, regionally, and internationally.
      FINDINGS: We found epidemic potential to vary within Africa, with regions where
      viral haemorrhagic fever outbreaks have previously occurred (eg, western Africa)
      and areas currently considered non-endemic (eg, Cameroon and Ethiopia) both
      ranking highly. Tracking transitions between stages showed how an index case can
      escalate into a widespread epidemic in the absence of intervention (eg, Nigeria
      and Guinea). Our analysis showed Chad, Somalia, and South Sudan to be highly
      susceptible to any outbreak at subnational levels. INTERPRETATION: Our analysis
      provides a unified assessment of potential epidemic trajectories, with the aim of
      allowing national and international agencies to pre-emptively evaluate needs and
      target resources. Within each country, our framework identifies at-risk
      subnational locations in which to improve surveillance, diagnostic capabilities,
      and health systems in parallel with the design of policies for optimal responses
      at each stage. In conjunction with pandemic preparedness activities, assessments
      such as ours can identify regions where needs and provisions do not align, and
      thus should be targeted for future strengthening and support. FUNDING: Paul G
      Allen Family Foundation, Bill & Melinda Gates Foundation, Wellcome Trust, UK
      Department for International Development.

PMID- 29031851
TI  - Constitutive Ret signaling leads to long-lasting expression of amphetamine
      induced place conditioning via elevation of mesolimbic dopamine.
AB  - Addictive drugs enhance dopamine release in the striatum, which can lead to
      compulsive drug-seeking after repeated exposure. Glial cell line-derived
      neurotrophic factor (GDNF) is an important regulator of midbrain dopamine
      neurons, and may play a mechanistic role in addiction-related behaviors. To
      elucidate the components of GDNF-signaling that contribute to addiction-related
      behaviors of place preference and its extinction, we utilized two genetically
      modified GDNF mouse models in an amphetamine-induced conditioned place preference
      (CPP) paradigm and evaluated how the behavioral findings correlate with dopamine
      signaling in the dorsal and ventral striatum. We utilized two knock-in mouse
      strains to delineate contributions of GDNF and Ret signaling using MEN2B mice
      (constitutively active GDNF receptor Ret), and GDNF hypermorphic mice (enhanced
      endogenous GDNF expression). The duration of amphetamine-induced CPP was greatly
      enhanced in MEN2B mice, but not in the GDNF hypermorphic mice. The enhanced
      duration of CPP was correlated with increased tyrosine hydroxylase (TH)
      expression and dopamine content in the ventral striatum. Together, our results
      suggest that downstream components of GDNF signaling, in this case Ret, may
      mediate persistent drug-seeking behavior through increased TH expression and
      dopamine levels in the mesolimbic dopamine neurons.

PMID- 29031853
TI  - Co-expression modules construction by WGCNA and identify potential prognostic
      markers of uveal melanoma.
AB  - Uveal melanoma is an aggressive cancer which has a high percentage recurrence and
      with a worse prognosis. Identify the potential prognostic markers of uveal
      melanoma may provide information for early detection of recurrence and treatment.
      RNA sequence data of uveal melanoma and patient clinic traits were obtained from
      The Cancer Genome Atlas (TCGA) database. Co-expression modules were built by
      weighted gene co -expression network analysis (WGCNA) and applied to investigate
      the relationship underlying modules and clinic traits. Besides, functional
      enrichment analysis was performed on these co-expression genes from interested
      modules. First, using WGCNA, identified 21 co-expression modules were constructed
      by the 10975 genes from the 80 human uveal melanoma samples. The number of genes
      in these modules ranged from 42 to 5091. Found four co -expression modules
      significantly correlated with three clinic traits (status, recurrence and
      recurrence Time). Module red, and purple positively correlated with patient's
      life status and recurrence Time. Module green positively correlates with
      recurrence. The result of functional enrichment analysis showed that the module
      magenta was mainly enriched genetic material assemble processes, the purple
      module was mainly enriched in tissue homeostasis and melanosome membrane and the
      module red was mainly enriched metastasis of cell, suggesting its critical role
      in the recurrence and development of the disease. Additionally, identified the
      hug gene (top connectivity with other genes) in each module. The hub gene
      SLC17A7, NTRK2, ABTB1 and ADPRHL1 might play a vital role in recurrence of uveal
      melanoma. Our findings provided the framework of co-expression gene modules of
      uveal melanoma and identified some prognostic markers might be detection of
      recurrence and treatment for uveal melanoma.

PMID- 29031852
TI  - Inhibition of Cdk5 rejuvenates inhibitory circuits and restores experience
      dependent plasticity in adult visual cortex.
AB  - Cyclin-dependent kinase 5 (Cdk5) acts as an essential modulator for neural
      development and neurological disorders. Here we show that Cdk5 plays a pivotal
      role in modulating GABAergic signaling and the maturation of visual system. In
      adult mouse primary visual cortex, Cdk5 formed complex with the GABA synthetic
      enzyme glutamate decarboxylase GAD67, but not with GAD65. In addition to
      enhancement in the surface level of NR2B-containing NMDA receptors, inhibition of
      Cdk5 reduced the protein levels of GADs and Otx2, while leaving intact the
      expression of vesicular GABA transporter and subunits of GABAA or AMPA receptors.
      Whole-cell patch-clamp recording in layer II/III pyramidal neurons revealed a
      decrease in the frequency of miniature inhibitory postsynaptic current (mIPSC).
      Consequently, pharmacological inhibition and genetic knockdown of Cdk5 in adult
      mice led to a restoration of juvenile-like ocular dominance plasticity in vivo
      and long-term synaptic potential in layer II/III induced by white matter
      stimulation in vitro. Interestingly, we did not observe an alteration of
      perineuronal nets of extracellular matrix, but a reinstatement of the capability
      to evoke long-term depression at inhibitory synapses (iLTD), which depended on
      presynaptic endocannabinoid receptors and was a sign of the rejuvenated GABAergic
      synapses. Enhancement of GABA signaling by diazepam impeded ocular dominance
      plasticity rescued by Cdk5 inhibition. These results thus suggest that a
      physiological role of Cdk5 in visual cortex is to consolidate and stabilize
      neural circuits through controlling GABAergic signaling.

PMID- 29031854
TI  - ANGPTL-4 induces diabetic retinal inflammation by activating Profilin-1.
AB  - Diabetic retinopathy (DR), the most common cause of irreversible blindness in
      working-age adults, results in central vision loss that is caused by
      microvascular damage to the inner lining of the back of the eye, the retina. The
      aim of this work was to assess the temporal relationships between angiopoietin
      like protein-4 (ANGPTL-4), a novel adipocytokine factor, and diabetic retinal
      inflammation and microvascular dysfunction. The downstream pathway(s) and
      upstream mediator(s) of ANGPTL-4 were then determined under high glucose (HG)
      conditions. Diabetic rats and control animals were randomly assigned to receive
      hypoxia inducible factor-1 alpha (HIF-1alpha) blockade (doxorubicin or shRNA) or
      vehicle for 8 weeks. Human retinal microvascular endothelial cells (HRMECs) were
      incubated with normal or high glucose, with or without blockade or recombinant
      proteins, for ANGPTL-4, HIF-1alpha, and vascular endothelial growth factor
      (VEGF). The levels of ANGPTL-4, profilin-1, HIF-1alpha, VEGF, interleukin 1 beta
      (IL-1beta), IL-6, and intercellular adherent molecule 1 (ICAM-1) in the rat
      retinas and HRMEC extracts were examined by Western blotting and real-time RT
      PCR. The levels of ANGPTL-4, profilin-1, HIF-1alpha, and VEGF protein and mRNA
      were significantly higher in the diabetic rats and HG-exposed HRMECs. ANGPTL-4
      was a potent modulator of increased inflammation, permeability, and angiogenesis
      via activation of the profilin-1 signaling pathway. Our results showed that
      ANGPTL-4 upregulation was induced by HG, which was dependent on HIF-1alpha
      activation that was also triggered by HG, both in vivo and in vitro. Our results
      suggest that targeting ANGPTL-4, alone or in combination with profilin-1, may be
      an effective therapeutic strategy and diagnostic screening biomarker for
      proliferative diabetic retinopathy and other vitreous-retinal inflammatory
      diseases.

PMID- 29031855
TI  - Furin deficiency in myeloid cells leads to attenuated revascularization in a
      mouse-model of oxygen-induced retinopathy.
AB  - Ischemic retinopathy is a vision-threatening disease associated with chronic
      retinal inflammation and hypoxia leading to abnormal angiogenesis. Furin, a
      member of the proprotein convertase family of proteins, has been implicated in
      the regulation of angiogenesis due to its essential role in the activation of
      several angiogenic growth factors, including vascular endothelial growth factor-C
      (VEGF-C), VEGF-D and transforming growth factor - beta (TGF- beta). In the
      present study, we evaluated expression of furin in the retina and its role in
      retinal angiogenesis. As both inflammation and hypoxia contribute to
      angiogenesis, the role of furin was evaluated using myeloid-cell specific furin
      knockout (KO) mice (designated LysMCre-fur(fl/fl)) both in developmental retinal
      angiogenesis as well as in hypoxia-driven angiogenesis using the oxygen-induced
      retinopathy (OIR) model. In the retina, furin expression was detected in
      endothelial cells, macrophages and, to some extent, in neurons. The rate of
      angiogenesis was not different in LysMCre-fur(fl/fl) mice when compared to their
      wild-type littermates during development. In the OIR model, the revascularization
      of retina was significantly delayed in LysMCre-fur(fl/fl) mice compared to their
      wild-type littermates, while there was no compensatory increase in the preretinal
      neovascularization in LysMCre-fur(fl/fl) mice. These results demonstrate that
      furin expression in myeloid cells plays a significant role in hypoxia-induced
      angiogenesis in retina.

PMID- 29031857
TI  - Defining Renal Neoplastic Disease, One Cell at a Time: Mass Cytometry, a New Tool
      for the Study of Kidney Biology and Disease.

PMID- 29031856
TI  - Relationship between Sigma-1 receptor and BDNF in the visual system.
AB  - Glaucoma is an incurable optic neuropathy characterized by dysfunction and death
      of retinal ganglion cells (RGCs). Brain derived neurotrophic factor (BDNF) is an
      essential neurotrophin that supports RGC function and survival. Despite BDNF's
      importance, our knowledge of molecular mechanisms that modulate BDNF processing
      and secretion is incomplete. Sigma-1 receptor (S1R) is associated with increased
      BDNF in hippocampus and with BDNF secretion by brain-derived astrocytes and
      neuronal cell lines. Much less is known about the relationship between S1R and
      BDNF in the visual system. Here, we examine how S1R activation and deletion alter
      expression of mature BDNF (mBDNF) and proBDNF in retina and cultured optic nerve
      head (ONH) astrocytes. For S1R activation, the S1R agonist (+)-pentazocine (PTZ,
      0.5 mg/kg) was administered by intraperitoneal injection to C57BL/6J mice, 3
      times per week, for 5 weeks. Expression of proBDNF and mBDNF was also examined in
      S1R knockout and age-matched C57BL/6J mice. In vitro, cultured ONH astrocytes
      were treated with 3 MUM PTZ for 24 h followed by collection of media and ONH
      astrocyte lysates. Results showed that treatment with (+)-PTZ increased mBDNF
      protein in both retina and hippocampus. In contrast, S1R deletion was associated
      with retinal mBDNF deficits. In ONH astrocytes S1R agonist (+)-PTZ significantly
      increased levels of secreted BDNF and proBDNF in cell lysates. These findings
      support a role for S1R in the modulation of BDNF levels within the retina and
      optic nerve head. Treatment with S1R agonists might provide benefit in diseases
      such as glaucoma by increasing BDNF levels from endogenous sources.

PMID- 29031858
TI  - Involvement of integrin beta1/FAK signaling in the analgesic effects induced by
      glial cell line-derived neurotrophic factor in neuropathic pain.
AB  - Treatment of neuropathic pain (NP) continues to be a clinical challenge and the
      underlying mechanisms of NP remain elusive. More evidence suggests that glial
      cell line-derived neurotrophic factor (GDNF) has potent anti-nociceptive effects
      on NP, but the underlying mechanisms are still largely unknown. Recent data have
      shown that integrin beta1 plays an important part in NP induction, and that the
      activity of integrin beta1 signaling is associated with the phosphorylation of
      the conserved threonines in the cytoplasmic domain and recruitment of focal
      adhesion kinase (FAK) to the integrin beta1 tail and phosphorylation. We assessed
      the effect of GDNF on integrinbeta1/FAK signaling in NP states. Immunostaining
      results showed that integrin beta1 was mainly observed in the superficial dorsal
      horn in the spinal cord of rats, and was mostly expressed in intrinsic neurons.
      Expression of p-integrin beta1 and the phosphorylation of integrin beta1
      associated FAK, but not integrin beta1 itself, was up-regulated after chronic
      constriction injury (CCI), which could be reversed by GDNF, and the effect of
      GDNF on integrin beta1/FAK signaling was inhibited by pre-treatment with RET
      function-blocking antibody (RET Ab). Moreover, pre-treatment with RET Ab could
      antagonize the effect of GDNF on inhibiting the NP induced by CCI. These data
      suggest that GDNF can regulate integrin beta1 activity via a RET-related
      mechanism.

PMID- 29031859
TI  - Neuroprotective Strategies in Neonatal Brain Injury.

PMID- 29031860
TI  - Children as Biomarker Orphans: Progress in the Field of Pediatric Biomarkers.

PMID- 29031861
TI  - The Benefits of Early Oral Nutrition in Mild Acute Pancreatitis.
AB  - OBJECTIVE: To determine whether early patient-directed oral nutrition in children
      with mild acute pancreatitis decreases the length of hospitalization without
      increasing complications. STUDY DESIGN: Hospitalized patients aged 2-21 years of
      age who met the criteria for acute pancreatitis based on the Revised Atlanta
      Classification were enrolled prospectively and allowed to eat by mouth at their
      discretion (patient-directed nutrition [PDN]). These patients were compared with
      a retrospective cohort of children who were allowed to eat based on traditional
      practices (treatment team-directed nutrition [TTDN]). Outcomes included length of
      hospitalization, time nil per os (NPO), and complications within 30 days of
      discharge. RESULTS: The study included 30 patients in the PDN group and 92
      patients in the TTDN group. Patients in the PDN group had a median length of stay
      of 48.5 hours (IQR 37-70 hours) compared with 93 hours (IQR 52-145 hours) in the
      TTDN group (P < .0001). Patients were NPO for a median of 14 hours (IQR 7-19.5
      hours) in the PDN group compared with 34 hours (IQR 19.3-55 hours) in the TTDN
      group (P < .0001). No patients in the PDN group developed complications within 30
      days of discharge. CONCLUSION: Early patient-directed oral nutrition in mild
      acute pancreatitis was well tolerated and resulted in decreased length of NPO
      status and hospitalization with no obvious complications. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01423786.

PMID- 29031862
TI  - PFAPA Syndrome in a Population with Endemic Familial Mediterranean Fever.
AB  - We reviewed the medical records of patients with periodic fever, aphthosis,
      pharyngitis, and adenitis (PFAPA) to investigate the clinical course, treatment
      response, and association with MEFV gene mutation. Familial Mediterranean fever
      should be considered in patients with PFAPA who do not respond to
      adenotonsillectomy.

PMID- 29031863
TI  - Validation of healthcare-associated infection surveillance in smaller Australian
      hospitals.
AB  - A validation study was conducted in smaller (<100 acute beds) Victorian hospitals
      to evaluate case detection for Staphylococcus aureus bloodstream (SAB),
      meticillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE)
      infections. Overall, 142 infections were identified in 20 hospitals. For routine
      surveillance of SAB events, sensitivity was 74.4% and specificity was 100.0%. For
      MRSA infections, sensitivity was 47.5% and specificity was 90.9%. All confirmed
      VRE infections were reported correctly. Of unreported SAB and MRSA infections,
      80% (N = 16) and 83.9% (N = 26) were community-associated infections,
      respectively. Future programme refinements include targeted education to ensure
      appropriate application of case definitions, particularly those including
      community onset.

PMID- 29031864
TI  - Bloodstream infections following different types of surgery in a Finnish tertiary
      care hospital, 2009-2014.
AB  - The risk and outcome of bloodstream infections (BSIs) were evaluated following
      surgery. BSIs were identified in Helsinki University Hospital during 2009-2014 as
      part of the national surveillance. Of 711 BSIs identified, 51% were secondary and
      49% primary. The rate was highest after cardiovascular surgery (8.7 per 1000
      procedures) and lowest after gynaecologic (1.0 per 1000). Surgical site infection
      was the most frequent source of secondary BSIs (34%) and 45% of primary BSIs were
      central-line-associated. The 28-day case fatality ranged from zero in
      gynaecology/obstetrics to 21% in cardiovascular surgery. Besides BSIs related to
      surgical site infections, half of BSIs were primary, providing additional foci
      for prevention.

PMID- 29031865
TI  - A neuropsychologist's view: Outcome after RF-ablation for mTLE.
AB  - Concern about postoperative worsening of cognitive functions after temporal lobe
      epilepsy surgery is an important issue. In this article we review our data on
      neuropsychological outcome after radiofrequency (RF) ablation of
      amygdalohippocampal complex (AHC). On a group level we found initial improvement
      in intelligence domains and unchanged memory scores one year after the surgery.
      During longitudinal follow-up, we found improvement in both intellectual and
      memory domains. This improvement was most pronounced up to two years after
      surgery. On an individual level, no patient worsened in any intellectual domain
      and most patients improved in memory. We hypothesize that this favorable outcome
      may be a consequence of minimization of collateral damage and incomplete
      destruction of target structures. We also summarize our experience with
      psychiatric complications of the procedure.

PMID- 29031866
TI  - Connectivity changes after laser ablation: Resting-state fMRI.
AB  - Resting-state functional magnetic resonance imaging (rsfMRI) is emerging as a
      useful tool in the multimodal assessment of patients with epilepsy. In pediatric
      patients who cannot perform task-based fMRI, rsfMRI may present an adjunct and
      alternative. Although changes in brain activation during task-based fMRI have
      been described after surgery for epilepsy, there is limited data on the role of
      postoperative rsfMRI. In this short review, we discuss the role of postoperative
      rsfMRI after laser ablation of seizure foci. By establishing standardized
      anesthesia protocols and imaging parameters, we have been able to perform serial
      rsfMRI at postoperative follow-up. The development of in-house software that can
      merge rsfMRI images to surgical navigation systems has allowed us to enhance the
      clinical applications of this technique. Resting-state fMRI after laser ablation
      has the potential to identify changes in connectivity, localize new seizure foci,
      and guide antiepileptic therapy. In our experience, rsfMRI complements
      conventional MR imaging and task-based fMRI for the evaluation of patients with
      seizure recurrence after laser ablation, and represents a potential noninvasive
      biomarker for functional connectivity.

PMID- 29031867
TI  - Influenza is more common than Middle East Respiratory Syndrome Coronavirus (MERS
      CoV) among hospitalized adult Saudi patients.
AB  - BACKGROUND: Since the initial description of Middle East Respiratory Syndrome
      Coronavirus (MERS-CoV), we adopted a systematic process of screening patients
      admitted with community acquired pneumonia. Here, we report the result of the
      surveillance activity in a general hospital in Saudi Arabia over a four year
      period. MATERIALS AND METHODS: All admitted patients with community acquired
      pneumonia from 2012 to 2016 were tested for MERS-CoV. In addition, testing for
      influenza viruses was carried out starting April 2015. RESULTS: During the study
      period, a total of 2657 patients were screened for MERS-CoV and only 20 (0.74%)
      tested positive. From January 2015 to December 2016, a total of 1644 patients
      were tested for both MERS-CoV and influenza. None of the patients tested positive
      for MERS-CoV and 271 (16.4%) were positive for influenza. The detected influenza
      viruses were Influenza A (107, 6.5%), pandemic 2009 H1N1 (n = 120, 7.3%), and
      Influenza B (n = 44, 2.7%). Pandemic H1N1 was the most common influenza in 2015
      with a peak in peaked October to December and influenza A other than H1N1 was
      more common in 2016 with a peak in August and then October to December.
      CONCLUSIONS: MERS-CoV was a rare cause of community acquired pneumonia and other
      viral causes including influenza were much more common. Thus, admitted patients
      are potentially manageable with Oseltamivir or Zanamivir therapy.

PMID- 29031868
TI  - Prevalence and Risk Factors for Chronic Venous Disease in the General Russian
      Population.
AB  - OBJECTIVE/BACKGROUND: The aim was to establish the prevalence of chronic venous
      disease (CVD) and its risk factors in the general population. METHODS: This was a
      population based, cross sectional study. In total, 703 residents aged > 18 years
      from the rural community of Kryukovo (Central Russia) were enrolled. Medical
      history was taken and clinical examination performed, documenting venous
      signs/symptoms. The CEAP classification of the most affected limb was used.
      Duplex ultrasound was performed to register morphological changes and reflux in
      deep and superficial veins. RESULTS: There were 63% women and 37% men (mean age
      53.5 years). CVD was found in 69.3%. Of all participants 4.7% were C0S and 34.3%
      were C1. Chronic venous insufficiency (C3-C6) was found in 8.2% and venous ulcers
      (C5-C6) in 1.1%. Venous pain, heaviness, fatigue, itching, and the sensation of
      swelling were documented in 14.8%, 36.3%, 32.8%, 7.0% and 29.1% of patients
      respectively. Family history was the significant risk factor for both CVD (hazard
      ratio [HR] 1.3) and primary varicose vein disease (HR 1.6; p < .01). Female sex
      was a risk factor only for CVD (HR 1.3; p < .01) but not for varicose veins. Age
      was a risk factor for CVD (HR 1.01) and for varicose veins (HR 1.02; p < .01).
      For women, number of births (HR 1.05; p < .05) and menopause (HR 1.3; p < .01)
      were risk factors for CVD. Menopause was a risk factor for varicose veins (HR
      2.0; p < .05). CONCLUSION: This study provides data on the prevalence of CVD,
      venous abnormalities and risk factors in Russia. The results contribute to
      already established data, giving a more complete outlook on the global prevalence
      of CVD.

PMID- 29031869
TI  - HashGO: hashing gene ontology for protein function prediction.
AB  - Gene ontology (GO) is a standardized and controlled vocabulary of terms that
      describe the molecular functions, biological roles and cellular locations of
      proteins. GO terms and GO hierarchy are regularly updated as the accumulated
      biological knowledge. More than 50,000 terms are included in GO and each protein
      is annotated with several or dozens of these terms. Therefore, accurately
      predicting the association between proteins and massive GO terms is rather
      challenging. To accurately predict the association between massive GO terms and
      proteins, we proposed a method called Hashing GO for protein function prediction
      (HashGO in short). HashGO firstly adopts a protein-term association matrix to
      store available GO annotations of proteins. Then, it tailors a graph hashing
      method to explore the underlying structure between GO terms and to obtain a
      series of hash functions to compress the high-dimensional protein-term
      association matrix into a low-dimensional one. Next, HashGO computes the semantic
      similarity between proteins based on Hamming distance on that low-dimensional
      matrix. After that, it predicts missing annotations of a protein based on the
      annotations of its semantic neighbors. Experimental results on archived GO
      annotations of two model species (Yeast and Human) show that HashGO not only more
      accurately predicts functions than other related approaches, but also runs faster
      than them.

PMID- 29031870
TI  - Novel Parameter to Predict Left Ventricular Filling Pressure: Product of Log B
      Type Natriuretic Peptide and Ratio of Mitral Inflow Early and Late Diastolic
      Filling Velocities.
AB  - BACKGROUND: Several echocardiographic parameters are currently used to evaluate
      left ventricular (LV) filling pressure. However, these parameters are not always
      consistent in the clinical setting. We aimed to determine a novel parameter by
      multiplying log B-type natriuretic peptide (lnBNP) and the ratio of mitral inflow
      early and late diastolic filling velocities (E/A) for the prediction of pulmonary
      capillary wedge pressure (PCWP). METHODS AND RESULTS: One hundred ninety-eight
      patients suspected of chronic heart failure were analyzed. The product of lnBNP
      and E/A (BNP * E/A) showed the highest correlation coefficient with mean PCWP (R
      = 0.7326) compared with E/A (R = 0.7010) and E/e' (R = 0.3922). Multivariate
      logistic regression analysis revealed that BNP * E/A was associated with elevated
      PCWP (odds ratio 1.640, 95% confidence interval 1.312-2.197; P <.01). In the
      receiver operating characteristic curve analysis for detecting elevated PCWP, BNP
      * E/A showed the largest area under the curve (AUC) compared with E/A and E/e'
      (0.880 vs 0.827 and 0.788, respectively; P <.05). BNP * E/A still showed large
      AUC (0.842) for detection of elevated PCWP in patients with normal LV ejection
      fraction. CONCLUSION: BNP * E/A is a useful parameter for detecting elevated PCWP
      regardless of the LV ejection fraction.

PMID- 29031871
TI  - Sirenomelia with VACTERL association-a rare anomaly.

PMID- 29031873
TI  - Does specialty matter? A survey on 176 Italian neurosurgeons and orthopedic spine
      surgeons confirms similar competency for common spinal conditions and supports
      multidisciplinary teams in comprehensive and complex spinal care.
AB  - BACKGROUND CONTEXT: Spine surgery is a multifaceted subspeciality requiring a
      breadth of knowledge and skill from different branches of medicine for the
      treatment of pathologies varying from degenerative to deformity, oncological, and
      trauma. PURPOSE: The aim of the study was to investigate the self-perceived
      competency of spine surgeons in relation to different types of spinal procedures.
      STUDY DESIGN/SETTING: This is a survey study. METHODS: We conducted a survey on
      176 surgeons (orthopedic surgeons and neurosurgeons). The instrument used for the
      assessment of the perceived ability was a survey consisting of 21 items
      (scenarios) developed and distributed through a professional online survey
      service to ensure confidentiality and anonymity. A newly proposed procedure
      specific rating survey was used for the evaluation. Kruskal-Wallis non-parametric
      test was used to assess validity. A p-value of <.05 was considered statistically
      significant. A Cronbach alpha value of >0.8 indicated reliability. RESULTS:
      Between the respondents (101), 47.5% were orthopedic surgeons and 52.5% were
      neurosurgeons. The internal consistency of the questionnaire was satisfactory
      (Cronbach alpha=0.93). For common spinal conditions, the orthopedic surgeons and
      the neurosurgeons perceived a similar competency. The neurosurgeons felt more
      competent in some cervical conditions (upper cervical procedures, myelopathy) and
      in neurologic tumors of the spine. The orthopedic surgeons felt more competent in
      deformities of the spine and in pelvic trauma. CONCLUSIONS: Self-perceived
      surgical competency for common spinal conditions is similar for orthopedic and
      neurosurgically trained spine surgeons. For less common conditions and clinical
      scenarios, the combination of both specialties seems to cover better the full
      spectrum of surgical care for spinal conditions. Multidisciplinary teams and
      comprehensive, multidisciplinary spinal surgical training should be considered to
      provide full coverage of spinal pathology.

PMID- 29031872
TI  - Accumulation and localization of macrophage phenotypes with human intervertebral
      disc degeneration.
AB  - BACKGROUND CONTEXT: Chronic inflammation is an important component of
      intervertebral disc (IVD) degeneration, but there is limited knowledge about the
      identity and source of inflammatory cells involved with the degenerative
      processes. Macrophages can exhibit multiple phenotypes and are known inflammatory
      regulators in many tissues, but their phenotypes have not been characterized in
      IVD degeneration. PURPOSE: We aimed to characterize accumulation and localization
      of macrophages in IVD degeneration. STUDY DESIGN/SETTING: This is an exploratory
      study to characterize macrophage phenotypes in human cadaver IVDs and the effects
      of injury and degeneration using multiple immunohistochemistry methods. OUTCOME
      MEASURES: Percent positivity of immunohistochemical markers specific for CCR7,
      CD163, and CD206, and qualitative assessments of dual immunofluorescence and
      immunostaining localization were the outcome measures. METHODS: Macrophages were
      identified in human cadaveric IVDs with immunohistochemistry using cell surface
      markers CCR7, CD163, and CD206, which are associated with proinflammatory M1,
      remodeling M2c, and anti-inflammatory M2a phenotypes, respectively. Variations in
      the accumulation and localization of macrophage markers with degenerative grade
      across subjects and within donors are described. RESULTS: Cells expressing all
      three macrophage markers were found in all degenerative IVDs, but not in the
      healthiest IVDs. Cells expressing CCR7 and CD163, but not CD206, significantly
      increased with degenerative grade. Many cells also co-expressed multiple
      macrophage markers. Across all degenerative grades, CCR7+ and CD163+ were
      significantly more present in unhealthy nucleus pulposus (NP), annulus fibrosus
      (AF), and end plate (EP) regions exhibiting structural irregularities and
      defects. Positively stained cells in the NP and AF closely resembled resident IVD
      cells, suggesting that IVD cells can express macrophage cell surface markers. In
      the EP, there were increasing trends of positively stained cells with atypical
      morphology and distribution, suggesting a source for exogenous macrophage
      infiltration into the IVD. CONCLUSIONS: Chronic inflammatory conditions of IVD
      degeneration appear to involve macrophages or macrophage-like cells, as
      expression of multiple macrophage markers increased with degeneration, especially
      around unhealthy regions with defects and the EP. Knowledge of macrophage
      phenotypes and their localization better elucidates the complex injury and repair
      processes in IVDs and may eventually lead to novel treatments.

PMID- 29031874
TI  - An update on the physiopathology and therapeutic management of cholestatic
      pruritus in children.
AB  - Pruritus is a disabling symptom accompanying chronic cholestasis. In extreme
      cases, the refractory nature of pruritus can result in a need for invasive
      therapies including liver transplantation. The pathogenesis of pruritus in
      cholestatic disease is poorly understood. It may involve a specific neural
      pathway (similar to that associated with pain) regulated by several pruritogenic
      substances such as bile acids, opioids, serotonin, and the more recently
      identified lysophosphatidic acid. While the therapeutic management of cholestatic
      pruritus is well established in adults, there is no consensus in children, in
      light of the difficulty of conducting controlled clinical studies. The currently
      recommended strategy to manage cholestatic pruritus in children is based on
      several lines of specific therapies that should be associated with skin hydration
      and with non-specific treatment of cholestasis including ursodeoxycholic acid.
      Pruritus should be assessed as objectively as possible between each line of
      therapy. Rifampicin, a potent CYP3A4 inducer, is the first-line treatment of
      cholestatic pruritus. Second-line therapies require evaluation of the child in an
      expert center and are discussed on a case-by-case basis depending on the
      underlying disease and the experience of the center. These include inhibitors of
      serotonin reuptake (sertraline), opioid antagonists (naloxone), or ASBT
      inhibitors. Invasive therapies such as biliary diversion or liver transplantation
      can also be proposed in the most severe cases. The aim of the current update is
      to review the physiopathologic mechanisms implicated in cholestatic pruritus and
      to propose potential therapeutic strategies in children.

PMID- 29031875
TI  - Soluble epoxide hydrolase inhibition with t-TUCB alleviates liver fibrosis and
      portal pressure in carbon tetrachloride-induced cirrhosis in rats.
AB  - BACKGROUND/AIMS: Fibrosis and increased intrahepatic vascular resistance are the
      hallmarks of chronic inflammatory disorders of the liver and cirrhosis.
      Inhibitors of the enzyme soluble epoxide hydrolase reduce fibrosis in several
      disease models. The present study aimed at investigating the effects of soluble
      epoxyhydrolase inhibition with t-TUCB in tetrachloride-induced cirrhosis in rats.
      METHODS: The models were established by CCl4 (2ml/kg) given subcutaneously for 14
      weeks. t-TUCB was concomitantly administered from the tenth week of modelling
      time. After the models were successfully built, the rats were anesthetized with
      sodium phenobarbital and portal pressure was determined in the groups. After
      that, the rats were killed and part of liver tissues were taken for histological
      analysis. In addition, the levels of intrahepatic inflammatory message factors
      were measured using real-time polymerase chain reaction (PCR) analysis. The
      remaining liver samples were processed for assessment of oxidative stress.
      RESULTS: t-TUCB administration significantly attenuated portal pressure relative
      to CCl4-only rats. This improvement was associated with decreased deposition of
      collagen in liver, which was supported by reduced mRNA expression of alpha-smooth
      muscle actin (alpha-SMA), Collagen I, Collagen III, transforming growth factor
      (TGF)-beta and tissue inhibitor of metalloproteinase-1 (TIMP-1) and increased
      matrix metalloproteinase-1, -13 (MMP-1, -13) mRNA expression. In addition, t-TUCB
      decreased the levels of proinflammatory cytokines, including IL-1beta, IL-6, IL
      10, tumor necrosis factor-alpha (TNF-alpha) and NF-kappaB, within cirrhotic
      hepatic tissue. Meanwhile, oxidative stress was also alleviated following
      inhibition of sEH in CCl4-induced models, as evidenced by down-regulated levels
      of malondialdehyde (MDA) and up-regulated levels of superoxide dismutase (SOD)
      and glutathione peroxidase (GSH-Px). CONCLUSION: The soluble epoxyhydrolase
      inhibitor, t-TUCB alleviates liver fibrosis and portal hypertension through
      attenuation of inflammatory response and oxidative stress in tetrachloride
      induced cirrhosis.

PMID- 29031876
TI  - Short communication: Association between udder health status and blood serum
      proteins in dairy cows.
AB  - The aim of this study was to investigate the association between udder health
      (UH) status and blood serum proteins (i.e., total protein, albumin, globulin, and
      albumin-to-globulin ratio) in dairy cows. Blood and milk samples were collected
      from 1,508 cows of 6 different breeds (Holstein Friesian, Brown Swiss, Jersey,
      Simmental, Rendena, and Alpine Grey) that were housed in 41 multibreed herds.
      Bacteriological analysis was performed on milk samples with somatic cell count
      (SCC) >100,000 cells/mL and bacteria identification was confirmed by multiplex
      PCR assays. Milk samples were grouped into 7 clusters of UH status: healthy (cows
      with milk SCC <100,000 cells/mL and not cultured); culture-negative samples with
      low, medium, or high SCC; and culture-positive samples with contagious,
      environmental, and opportunistic intramammary infections. Data of blood serum
      proteins were analyzed using a linear mixed model that included the fixed effects
      of stage of lactation, parity, breed, herd productivity (high or low production)
      and UH status, and the random effect of herd-date within herd productivity.
      Culture-negative samples with high milk SCC, which were most likely undergoing a
      strong inflammatory response and whose pathogens could not be isolated because
      they were engulfed by macrophages or because they had already cleared, and milk
      samples infected by contagious and environmental bacteria were associated with
      greater globulin concentrations (and lower albumin-to-globulin ratio) in blood.
      Variation in blood serum proteins seems to be associated with inflammatory status
      rather than infection, as serum globulin significantly increased in UH status
      groups with the highest milk SCC and no differences were observed among
      intramammary infections pathogens. Blood serum proteins can be a mammary gland
      inflammation indicator, but cannot be used to differentiate among different UH
      status groups.

PMID- 29031877
TI  - Individual variation of the extent of milk fat depression in dairy ewes fed fish
      oil: Milk fatty acid profile and mRNA abundance of candidate genes involved in
      mammary lipogenesis.
AB  - Dairy ewes are less prone than cows to milk fat depression (MFD) but suffer from
      this syndrome when marine lipids are added to their diet to modulate milk fatty
      acid (FA) profile. However, there are large individual differences in MFD extent,
      and the reasons behind this variability are uncertain. On this basis, a study was
      conducted in lactating sheep to test the hypotheses that individual
      susceptibility to the low-fat milk condition may be explained by differences in
      (1) the milk concentration of some FA, particularly antilipogenic FA, or (2) the
      transcriptional regulation of mammary lipogenesis. For 5 wk, 15 ewes received a
      total mixed ration supplemented with 0 (control; n = 5) or 20 g of fish oil/kg of
      dry matter [10 animals selected out of 22 and divided into those showing marked
      (RESPON+; n = 5) or mild (RESPON-; n = 5) MFD]. Milk production and composition,
      including a comprehensive FA profile, were examined on 3 consecutive days before
      and after treatments. Candidate gene expression was also analyzed before the
      start of the trial and at its end using RNA isolated from milk somatic cells.
      According to the experimental design, the fish-oil-induced decrease in milk fat
      concentration was much stronger in RESPON+ (-25.4%) than in RESPON- (-7.7%). Milk
      from all ewes fed the supplemented diet showed rather uniform changes in the
      proportion of potentially healthy FA (such as cis-9,trans-11 18:2, trans-11 18:1,
      or 20:5n-3) and of those with confirmed or putative antilipogenic effects (e.g.,
      cis-9 16:1, trans-10 and cis-11 18:1, trans-9,cis-11 18:2, and 10-oxo-18:0),
      without significant variation between RESPON+ and RESPON-. It was not possible to
      relate the very few exceptions to this general trend (e.g., in cis-7 16:1 and
      22:6n-3) to responsiveness. Major mechanisms involved in mammary lipogenesis,
      specifically the uptake and de novo synthesis of FA, appeared to be unequally
      inhibited in ewes displaying different degrees of MFD, with molar yields of >16C
      FA being unaffected in RESPON-. However, this was not reflected in candidate gene
      expression. Supplementation with fish oil showed a tendency to lower the mRNA
      abundance of lipogenic genes such as ACSS2, FASN, LPIN1, FADS2, and INSIG1, but
      only SCD and GPAT4 tended to differ between RESPON- and RESPON+. Overall, these
      results offer no convincing support for the initial hypotheses, so further
      research must be pursued to explain the individual variation in MFD severity.

PMID- 29031878
TI  - Retention and transport of mecoprop on acid sandy-loam soils.
AB  - Interaction with soil components is one of the key processes governing the fate
      of agrochemicals in the environment. In this work, we studied the adsorption /
      desorption and transport of mecoprop (methylchlorophenoxypropionic acid or MCPP)
      in four acid sandy-loam soils with different organic matter contents. Kinetics of
      adsorption and adsorption/desorption at equilibrium were studied in batch
      experiments, whereas transport was studied in laboratory columns. Adsorption and
      desorption were found to be linear or nearly-linear. The kinetics of mecoprop
      adsorption were relatively fast in all cases (less than 24h). Adsorption and
      desorption were adequately described by the linear and Freundlich models, with KF
      values that ranged from 0.7 to 8.8Ln umol1-nkg-1 and KD values from 0.3 to 3.6Lkg
      1. The results of the transport experiments showed that the retention of mecoprop
      by soil was very low (less than 6.2%). The retention of mecoprop by the soils in
      all experiments increased with organic matter content. Overall, it was observed
      that mecoprop was weakly adsorbed by the soils, what would result in a high risk
      of leaching of this compound in the environment.

PMID- 29031879
TI  - The effects of extracellular polymeric substances on magnetic iron oxide
      nanoparticles stability and the removal of microcystin-LR in aqueous
      environments.
AB  - The behaviors of nanoparticles rely on the aqueous condition such as natural
      organic matter (NOM). Therefore the presence of NOM would influence the
      interaction of nanoparticles with other substances possibly. Here, microcystin-LR
      (MC-LR) adsorption on iron oxide nanoparticles (IONPs) was studied in an aqueous
      solution with different types of NOM, including extracellular polymeric
      substances (EPS) from cyanobacteria and alginic acid sodium salt (AASS) from
      brown algae. Results revealed that EPS played an important role in stabilizing
      IONPs and in the toxin adsorption efficiency. The stability of IONPs was heavily
      depended on the concentration and type of NOM, which can affect the surface
      charge of IONPs significantly in solution. The enhanced stability of IONPs was
      due to the electrostatic interactions. Adsorption kinetics and isotherm studies
      confirmed that NOM can affect the IONPs' adsorption efficiency, and pseudo-second
      order kinetics better explained this process. The removal efficiency for MC-LR
      decreased in the presence of NOM (Control > EPS-M1 > AASS > EPS-M9), indicating
      that NOM and MC-LR compete for limited adsorption sites. The presence of NOM in a
      eutrophic environment stabilized the IONPs while inhibiting the MC-LR removal
      efficiency. This investigation emphasized the negative effect of cyanobacterial
      EPS on the removal of microcystins when using magnetic separation technology. And
      this results could also be used to model the transportation of iron minerals
      carrying toxic substances in aqueous environment.

PMID- 29031880
TI  - Assisted phytoremediation of heavy metal contaminated soil from a mined site with
      Typha latifolia and Chrysopogon zizanioides.
AB  - Chemically assisted phytoremediation is fast gaining attention as a biotechnology
      to accelerate heavy metal removal from contaminated substrates, but how different
      chemical amendments affect the process remains an important research question.
      Here, bioaccumulation factor (BAF), translocation factor (TF), removal efficiency
      (RE) and uptake of Hg, As, Pb, Cu and Zn by cattail (Typha latifolia) and vetiver
      (Chrysopogon zizanioides) were quantified in a potted experiment to determine the
      effects of amendments on the phytoremediation success. Baseline concentrations of
      heavy metals within the studied mined site were determined. The experiment
      involved three soil treatments (each comprising 16 samples amended with 0.05mol/L
      ethylene di-aminetetraacetic acid (EDTA), 3g of aluminum sulfate [Al2(SO4)3], and
      unamended control) transplanted with equal numbers of vetiver and cattail. Growth
      performance (height) of plant species was monitored every two weeks. Sixteen
      weeks after transplanting, heavy metal levels in plant and soil samples were
      quantified following standard protocols, and the biomass and root length measured
      for each plant species. Results indicated strong negative impact of mining
      activities on heavy metal levels of soil in the study area. Soil amendment
      considerably enhanced the BAF, TF, RE and uptake but the effect varied with plant
      species and heavy metal in question. The amendment also stimulated strong
      positive correlation between RE and BAF, TF and metal uptake, and generally did
      not show any negative effects on plant growth performance. In general, soil
      amendment aided the accumulation and translocation of heavy metals in the plant
      species studied, and could be explored for cleaning up contaminated sites.

PMID- 29031881
TI  - Beyond variability: Subjective timing and the neurophysiology of motor cognition.
AB  - BACKGROUND: Movement simulation helps increasing the chances to reach goals. A
      cognitive task used to study the neuro-behavioral aspects of movement simulation
      is mental rotation: people mentally re-orient rotated pictures of hands. However,
      the involvement of the primary motor cortex (M1) in mental rotation is largely
      controversial. HYPOTHESIS: Such inconsistency could arise from potential
      methodological flaws in experimental procedures and data analysis. In particular,
      until now, the timing of M1 activity has been computed in absolute terms: from
      the onset of mental rotation (onset-locked), neglecting intra- and inter-subject
      variability. METHODS: A novel phase-locked approach is introduced to synchronize
      the same phases of cognitive processing among different subjects and sessions.
      This approach was validated in the particular case of corticospinal excitability
      of the motor cortex during mental rotation. RESULTS: We identified the relative
      time-windows during which the excitability of M1 is effector-specifically
      modulated by different features of mental rotation. These time windows correspond
      to the 55%-85% of the subjective timing. CONCLUSIONS: In sum, (i) we introduce a
      new method to study the neurophysiology of motor cognition, and (ii) validating
      this method, we shed new light on the involvement of M1 in movement simulation.

PMID- 29031882
TI  - Long-term outcomes after noncurative endoscopic resection of early gastric
      cancer: the optimal time for additional endoscopic treatment.
AB  - BACKGROUND AND AIMS: We aimed to evaluate long-term outcomes with noncurative
      endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) and
      surveillance strategies such as the optimal time for additional endoscopic
      treatment in patients with noncurative ESD. METHODS: Of 2527 patients who
      underwent gastric ESD for EGC, 512 (20.3%) patients with noncurative resection
      were reviewed. Noncurative resection is defined as positive resected margins on
      histology, lymphovascular infiltration, or beyond the expanded criteria for ESD.
      RESULTS: The mean +/- standard deviation follow-up duration was 79.0 +/- 55.7
      months. A total of 264 patients (51.6%) and 50 patients (9.8%) underwent surgery
      and endoscopic treatment after noncurative resection, respectively, whereas 198
      patients (38.7%) were observed. Cancer-specific survival and disease-free
      survival rates were significantly different among the surgery, other endoscopic
      treatment, and observation groups (96.7%, 86.8%, and 86.2%, respectively; P
      =.030; and 92.5%, 73.6%, and 63.0%, respectively; P < .001). When patients who
      underwent surgery were excluded, the disease-free survival rate of recurrence was
      not significantly different between the endoscopic treatment and observation
      groups (73.6% vs 63.0%; P = .548). To exclude the potential for the presence of
      lymph node metastasis, we further analyzed disease-free survival of local
      recurrence by comparing the patients with only a positive lateral resection
      margin. The disease-free survival rate was higher in the endoscopic treatment
      group than in the observation group (89.2% vs 69.1%; P = .023). Moreover,
      additional endoscopic treatment within 3 months showed significant associations
      with lower risk of local recurrence on multivariate analysis (hazard ratio,
      0.017; 95% confidence interval, 0.002-0.260; P = .003). CONCLUSIONS: In patients
      with noncurative ESD, additional surgery showed a better long-term outcome;
      moreover, when a positive lateral resection margin was the only noncurative
      factor, additional endoscopic treatment within 3 months could be considered to
      improve disease-free survival.

PMID- 29031883
TI  - Antihypertensive pharmacotherapy for prevention of sudden cardiac death in
      hypertensive individuals: A Cochrane review summary.

PMID- 29031884
TI  - Human sperm cryopreservation in cancer patients: Links with deprivation and
      mortality.
AB  - Evidence is mounting for a relationship between human semen quality and
      environmental/lifestyle/socioeconomic factors including long term health outcomes
      such as mortality. The relationship between pre-freeze and post-thaw semen
      quality in cancer patients and these factors are unknown. Frozen semen from 217
      cancer patients was thawed and analysed using a validated CASA method. Post-thaw
      quality was matched and compared with WHO semen analysis performed prior to
      storage. The English Indices of Deprivation 2010 were matched with patients and
      then examined for relationships with pre-freeze and post-thaw semen quality.
      There is a relationship between semen quality and deprivation in cancer patients.
      Compared with pre-freeze semen quality, post-thaw semen quality has a stronger
      relationship with deprivation. Sperm cryopreservation may have potential as a
      systemic health diagnostic test and is predictive of cancer patient mortality.

PMID- 29031885
TI  - Multiple signal-amplification via Ag and TiO2 decorated 3D nitrogen doped
      graphene hydrogel for fabricating sensitive label-free photoelectrochemical
      thrombin aptasensor.
AB  - In this study, Ag/TiO2/3D nitrogen doped graphene hydrogel (3DNGH) was prepared
      for the first time and the photocurrent intensity of this material was greatly
      enhanced, which was attributed to the multiple enhancements accomplished in one
      step. The porous structure of 3DNGH could provide an exceptionally large
      accessible surface area, which was beneficial for the anchoring of Ag and TiO2
      nanoparticles. The introduction of nitrogen doped graphene and metal
      nanoparticles was capable to facilitate the charge separation efficiency and
      accelerate the transfer rate of the photogenerated electron-hole pairs. Then the
      photoelectrochemical performance was further amplified by the localized surface
      plasmon resonance of Ag nanoparticles. On the basis of excellent PEC properties
      of Ag/TiO2/3DNGH, a sensitive label-free PEC sensor has been established for the
      determination of thrombin successfully. This proposed PEC biosensor exhibited
      good PEC performances with a wide linear in the range from 0.01p.M. to 10p.M. as
      well as a relative low detection limit of 3 fM (S/N = 3), indicating that
      Ag/TiO2/3DNGH would serve as a promising photoactive material in the applications
      of PEC biosensors.

PMID- 29031886
TI  - ZIF-67 derived porous Co3O4 hollow nanopolyhedron functionalized solution-gated
      graphene transistors for simultaneous detection of glucose and uric acid in
      tears.
AB  - Biomarkers in tears have attracted much attention in daily healthcare sensing and
      monitoring. Here, highly sensitive sensors for simultaneous detection of glucose
      and uric acid are successfully constructed based on solution-gated graphene
      transistors (SGGTs) with two separate Au gate electrodes, modified with GOx-CHIT
      and BSA-CHIT respectively. The sensitivity of the SGGT is dramatically improved
      by co-modifying the Au gate with ZIF-67 derived porous Co3O4 hollow
      nanopolyhedrons. The sensing mechanism for glucose sensor is attributed to the
      reaction of H2O2 generated by the oxidation of glucose near the gate, while the
      sensing mechanism for uric acid is due to the direct electro-oxidation of uric
      acid molecules on the gate. The optimized glucose and uric acid sensors show the
      detection limits both down to 100nM, far beyond the sensitivity required for non
      invasive detection of glucose and uric acid in tears. The glucose and uric acid
      in real tear samples was quantitatively detected at 323.2 +/- 16.1MUM and 98.5 +/
      16.3MUM by using the functionalized SGGT device. Due to the low-cost, high
      biocompatibility and easy-fabrication features of the ZIF-67 derived porous Co3O4
      hollow nanopolyhedron, they provide excellent electrocatalytic nanomaterials for
      enhancing sensitivity of SGGTs for a broad range of disease-related biomarkers.

PMID- 29031887
TI  - Direct colorimetric detection of unamplified pathogen DNA by dextrin-capped gold
      nanoparticles.
AB  - The interaction between gold nanoparticles (AuNPs) and nucleic acids has
      facilitated a variety of diagnostic applications, with further diversification of
      synthesis match bio-applications while reducing biotoxicity. However, DNA
      interactions with unique surface capping agents have not been fully defined.
      Using dextrin-capped AuNPs (d-AuNPs), we have developed a novel unamplified
      genomic DNA (gDNA) nanosensor, exploiting dispersion and aggregation
      characteristics of d-AuNPs, in the presence of gDNA, for sequence-specific
      detection. We demonstrate that d-AuNPs are stable in a five-fold greater salt
      concentration than citrate-capped AuNPs and the d-AuNPs were stabilized by single
      stranded DNA probe (ssDNAp). However, in the elevated salt concentrations of the
      DNA detection assay, the target reactions were surprisingly further stabilized by
      the formation of a ssDNAp-target gDNA complex. The results presented herein lead
      us to propose a mechanism whereby genomic ssDNA secondary structure formation
      during ssDNAp-to-target gDNA binding enables d-AuNP stabilization in elevated
      ionic environments. Using the assay described herein, we were successful in
      detecting as little as 2.94 fM of pathogen DNA, and using crude extractions of a
      pathogen matrix, as few as 18 spores/uL.

PMID- 29031888
TI  - Below the surface: Parents' views on the factors that influence treatment
      adherence in paediatric burn scar management - A qualitative study.
AB  - INTRODUCTION: Parents have a crucial role to play in burn scar management for
      their children at a time that is extremely stressful for them and their child.
      Scar management treatments such as pressure garment therapy (PGT) require high
      levels of adherence. There has been a lack of research into the factors that may
      influence adherence in paediatric burn scar management. This qualitative research
      study has investigated parents' experiences of scar management and their attempts
      to adhere to treatment at home. The aim of this paper is to outline parents'
      views on the factors that influence adherence. METHODS: 25 parents of paediatric
      and adolescent burn patients took part in semi-structured interviews.
      Participants were recruited from three UK burns services. Interviews were
      conducted in a participant-focussed manner and topics for discussion included
      parents' accounts of treatment and their experience of PGT. A thematic analysis
      was undertaken. RESULTS: Four overarching themes describe parents' views and
      experiences of scar management and adherence. These are the transition from
      hospital to home; the practical realities of treatment; the emotional labour
      involved in treatment and; negotiating treatment and regime. The transition from
      hospital to home is a significant event for parents. They may be apprehensive
      about this at the same time as they desire that they and their child return to
      some sense of normality following the burn injury. Parents are required to adopt
      the role of therapeutic caregiver upon transition from hospital to home.
      Adherence to scar management is influenced by the practical realities of
      maintaining treatment (routine, division of care labour, hospital appointments)
      and the emotional labour involved in doing so. The latter demands that parents
      manage their own and their children's emotions. Approaches to adherence were
      often described as flexible in response to these influences. CONCLUSIONS: Some
      parents negotiate the realities and demands of scar management successfully,
      whereas others do not. The emotional labour experienced by parents and their
      ability to cope with this is often a strong influence on their views regarding
      adherence to scar management. Further research is needed to explore how burns
      services and staff manage this at present, and whether simple interventions can
      help with the key practical and emotional influences on treatment adherence.

PMID- 29031889
TI  - Outcomes important to burns patients during scar management and how they compare
      to the concepts captured in burn-specific patient reported outcome measures.
AB  - BACKGROUND: Pressure garment therapy (PGT) is an established treatment for the
      prevention and treatment of hypertrophic scarring; however, there is limited
      evidence for its effectiveness. Burn survivors often experience multiple issues
      many of which are not adequately captured in current PGT trial measures. To
      assess the effectiveness of PGT it is important to understand what outcomes
      matter to patients and to consider whether patient-reported outcome measures
      (PROMs) can be used to ascertain the effect of treatments on patients' health
      related quality of life. This study aimed to (a) understand the priorities and
      perspectives of adult burns patients and the parents of burns patients who have
      experienced PGT via in-depth qualitative data, and (b) compare these with the
      concepts captured within burn-specific PROMs. METHODS: We undertook 40 semi
      structured interviews with adults and parents of paediatric and adolescent burns
      patients who had experienced PGT to explore their priorities and perspectives on
      scar management. Interviews were audio-recorded, transcribed and thematically
      analysed. The outcomes interpreted within the interview data were then mapped
      against the concepts captured within burn-specific PROMs currently in the
      literature. RESULTS: Eight core outcome domains were identified as important to
      adult patients and parents: (1) scar characteristics and appearance, (2) movement
      and function, (3) scar sensation, (4) psychological distress, adjustments and a
      sense of normality, (5) body image and confidence, (6) engagement in activities,
      (7) impact on relationships, and (8) treatment burden. CONCLUSIONS: The outcome
      domains presented reflect a complex holistic patient experience of scar
      management and treatments such as PGT. Some currently available PROMs do capture
      the concepts described here, although none assess psychological adjustments and
      attainment of a sense of normality following burn injury. The routine use of
      PROMs that represent patient experience and their relative contribution to trial
      outcome assessment versus clinical measures is now a matter for further research
      and debate.

PMID- 29031890
TI  - Changing perspectives in atopic dermatitis.
AB  - Atopic dermatitis (AD) is a multifaceted disease that involves a complex
      interplay between the skin and the immune system. The course of the disease
      depends strongly on the genetic background of the patient and on yet poorly
      defined environmental factors. Changes in lifestyle could be behind the dramatic
      rise in the prevalence of AD across continents; including hygienic conditions,
      food, social habits, skin microbiome or exposure to a number of allergens.
      Although AD typically develops in childhood and disappears after a few years, in
      a relatively large number of patients it continues into adulthood. Adult AD can
      also appear de novo but it is often underdiagnosed and its treatment can be
      challenging. New, highly effective drugs are being developed to manage moderate
      and severe forms of the disease in adults. In this review, we highlight the most
      recent developments in diagnostic tools, current insights into the mechanistic
      basis of this disease, and therapeutic innovations.

PMID- 29031891
TI  - Low efficacy of atopy patch test in predicting tolerance development in non-IgE
      mediated cow's milk allergy.
AB  - BACKGROUND: The food atopy patch (APT) test has been used in previous studies to
      help the diagnosis of non-IgE mediated food allergies (FA). The aim of this study
      was to evaluate the efficacy of different cow's milk APT preparations to predict
      oral tolerance in children with previous non-IgE-mediated cow's milk allergy
      (CMA) diagnosis. METHODS: Thirty-two patients non-IgE-mediated CMA diagnosed by
      oral food challenge (OFC) were enrolled to perform APT with three different cow's
      milk preparations (fresh, 2% in saline solution, 2% in petrolatum) and comparing
      with a new OFC after at least three months of diet exclusion. RESULTS: Only six
      (18.7%) subjects presented positive OFC to cow's milk. No differences in gender,
      onset symptoms age, OFC age, Z-score, and exclusion period were found between
      positive and negative OFC patients. Preparations using fresh milk and powdered
      milk in petrolatum presented sensitivity equal to zero and specificity 92.3% and
      96.1%. The preparation using powdered milk in saline solution showed sensitivity
      and specificity of 33.3% and 96.1%. Two patients presented typical IgE symptoms
      after OFC. CONCLUSION: Cow's milk APT presented a low efficacy to predict
      tolerance in patients with previous non-IgE-mediated CMA and should not be used
      in clinical routine. The presence of typical IgE reactions after OFC hallmark the
      necessity of previous IgE-mediated investigation for this patient group.

PMID- 29031893
TI  - In an in-vitro model using human fetal membranes, 17-alpha hydroxyprogesterone
      caproate is not an optimal progestogen for inhibition of fetal membrane
      weakening.
AB  - BACKGROUND: The progestogen 17-alpha hydroxyprogesterone caproate (17-OHPC) is 1
      of only 2 agents recommended for clinical use in the prevention of spontaneous
      preterm delivery, and studies of its efficacy have been conflicting. We have
      developed an in-vitro model to study the fetal membrane weakening process that
      leads to rupture in preterm premature rupture of the fetal membranes (pPROM).
      Inflammation/infection associated with tumor necrosis factor-alpha (TNF-alpha)
      induction and decidual bleeding/abruption associated thrombin release are leading
      causes of preterm premature rupture of the fetal membranes. Both agents (TNF
      alpha and thrombin) cause fetal membrane weakening in the model system.
      Furthermore, granulocyte-macrophage colony-stimulating factor (GM-CSF) is a
      critical intermediate for both TNF-alpha and thrombin-induced fetal membrane
      weakening. In a previous report, we demonstrated that 3 progestogens,
      progesterone, 17-alpha hydroxyprogesterone (17-OHP), and medroxyprogesterone
      acetate (MPA), each inhibit both TNF-alpha- and thrombin-induced fetal membrane
      weakening at 2 distinct points of the fetal membrane weakening pathway. Each
      block both the production of and the downstream action of the critical
      intermediate granulocyte-macrophage colony-stimulating factor. OBJECTIVE: The
      objective of the study was to characterize the inhibitory effects of 17-OHPC on
      TNF-alpha- and thrombin-induced fetal membrane weakening in vitro. STUDY DESIGN:
      Full-thickness human fetal membrane fragments from uncomplicated term repeat
      cesarean deliveries were mounted in 2.5 cm Transwell inserts and cultured
      with/without 17-alpha hydroxyprogesterone caproate (10-9 to 10-7 M). After 24
      hours, medium (supernatant) was removed and replaced with/without the addition of
      tumor necrosis factor-alpha (20 ng/mL) or thrombin (10 U/mL) or granulocyte
      macrophage colony-stimulating factor (200 ng/mL). After 48 hours of culture,
      medium from the maternal side compartment of the model was assayed for
      granulocyte-macrophage colony-stimulating factor and the fetal membrane fragments
      were rupture strength tested. RESULTS: Tumor necrosis factor-alpha and thrombin
      both weakened fetal membranes (43% and 62%, respectively) and increased
      granulocyte-macrophage colony-stimulating factor levels (3.7- and 5.9-fold,
      respectively). Pretreatment with 17-alpha hydroxyprogesterone caproate inhibited
      both tumor necrosis factor-alpha- and thrombin-induced fetal membrane weakening
      and concomitantly inhibited the induced increase in granulocyte-macrophage colony
      stimulating factor in a concentration-dependent manner. However, contrary to our
      prior reports regarding progesterone and other progestogens, 17-alpha
      hydroxyprogesterone caproate did not also inhibit granulocyte-macrophage colony
      stimulating factor-induced fetal membrane weakening. CONCLUSION: 17-Alpha
      hydroxyprogesterone caproate blocks tumor necrosis factor-alpha- and thrombin
      induced fetal membrane weakening by inhibiting the production of granulocyte
      macrophage colony-stimulating factor. However, 17-alpha hydroxyprogesterone
      caproate did not also inhibit granulocyte-macrophage colony-stimulating factor
      induced weakening. We speculate that progestogens other than 17-alpha
      hydroxyprogesterone caproate may be more efficacious in preventing preterm
      premature rupture of the fetal membranes-related spontaneous preterm birth.

PMID- 29031892
TI  - Altered angiogenesis as a common mechanism underlying preterm birth, small for
      gestational age, and stillbirth in women living with HIV.
AB  - BACKGROUND: Angiogenic processes in the placenta are critical regulators of fetal
      growth and impact birth outcomes, but there are limited data documenting these
      processes in HIV-infected women or women from low-resource settings. OBJECTIVE:
      We sought to determine whether angiogenic factors are associated with adverse
      birth outcomes in HIV-infected pregnant women started on antiretroviral therapy.
      STUDY DESIGN: This is a secondary analysis of samples collected as part of a
      clinical trial randomizing pregnant women and adolescents infected with HIV to
      lopinavir/ritonavir-based (n = 166) or efavirenz-based (n = 160) antiretroviral
      therapy in Tororo, Uganda. Pregnant women living with HIV were enrolled between
      12-28 weeks of gestation. Plasma samples were evaluated for angiogenic biomarkers
      (angiopoietin-1, angiopoietin-2, vascular endothelial growth factor, soluble fms
      like tyrosine kinase-1, placental growth factor, and soluble endoglin) by enzyme
      linked immunosorbent assay between: 16-<20, 20-<24, 24-<28, 28-<32, 32-<36, 36
      <37 weeks of gestation. The primary outcome was preterm birth. RESULTS: In all,
      1115 plasma samples from 326 pregnant women and adolescents were evaluated. There
      were no differences in angiogenic factors according to antiretroviral therapy
      group (P > .05 for all). The incidence of adverse birth outcomes was 16.9% for
      spontaneous preterm births, 25.6% for small-for-gestational-age births, and 2.8%
      for stillbirth. We used linear mixed effect modelling to evaluate longitudinal
      changes in angiogenic factor concentrations between birth outcome groups
      adjusting for gestational age at venipuncture, maternal age, body mass index,
      gravidity, and the interaction between treatment arm and gestational age. Two
      angiogenic factors-soluble endoglin and placental growth factor-were associated
      with adverse birth outcomes. Significantly higher concentrations of soluble
      endoglin throughout gestation were found in study participants destined to
      deliver preterm [likelihood ratio test, chi2(1) = 12.28, P < .0005] and in those
      destined to have stillbirths [chi2(1) = 5.67, P < .02]. By contrast,
      significantly lower concentrations of placental growth factor throughout
      gestation were found in those destined to have small-for-gestational-age births
      [chi2(1) = 7.89, P < .005] and in those destined to have stillbirths [chi2(1) =
      21.59, P < .0001]. CONCLUSION: An antiangiogenic state in the second or third
      trimester is associated with adverse birth outcomes, including stillbirth in
      women and adolescents living with HIV and receiving antiretroviral therapy.

PMID- 29031896
TI  - Thermoresponsive beta-glucan-based polymers for bimodal immunoradiotherapy - Are
      they able to promote the immune system?

PMID- 29031895
TI  - Chronic pelvic pain in an interdisciplinary setting: 1-year prospective cohort.
AB  - BACKGROUND: Chronic pelvic pain affects ~15% of women, and presents a challenging
      problem for gynecologists due to its complex etiology involving multiple
      comorbidities. Thus, an interdisciplinary approach has been proposed for chronic
      pelvic pain, where these multifactorial comorbidities can be addressed by
      different interventions at a single integrated center. Moreover, while cross
      sectional studies can provide some insight into the association between these
      comorbidities and chronic pelvic pain severity, prospective longitudinal cohorts
      can identify comorbidities associated with changes in chronic pelvic pain
      severity over time. OBJECTIVE: We sought to describe trends and factors
      associated with chronic pelvic pain severity over a 1-year prospective cohort at
      an interdisciplinary center, with a focus on the role of comorbidities and
      controlling for baseline pain, demographic factors, and treatment effects. STUDY
      DESIGN: This was a prospective 1-year cohort study at an interdisciplinary
      tertiary referral center for pelvic pain and endometriosis, which provides
      minimally invasive surgery, medical management, pain education, physiotherapy,
      and psychological therapies. Exclusion criteria included menopause or age >50
      years. Sample size was 296 (57% response rate at 1 year; 296/525). Primary
      outcome was chronic pelvic pain severity at 1 year on an 11-point numeric rating
      scale (0-10), which was categorized for ordinal regression (none-mild 0-3,
      moderate 4-6, severe 7-10). Secondary outcomes included functional quality of
      life and health utilization. Baseline comorbidities were endometriosis, irritable
      bowel syndrome, painful bladder syndrome, abdominal wall pain, pelvic floor
      myalgia, and validated questionnaires for depression, anxiety, and
      catastrophizing. Multivariable ordinal regression was used to identify baseline
      comorbidities associated with the primary outcome at 1 year. RESULTS: Chronic
      pelvic pain severity decreased by a median 2 points from baseline to 1 year (6/10
      4/10, P < .001). There was also an improvement in functional quality of life (42
      29% on the pain subscale of the Endometriosis Health Profile-30, P < .001), and a
      reduction in subjects requiring a physician visit (73-36%, P < .001) or emergency
      visit (24-11%, P < .001) in the last 3 months. On multivariable ordinal
      regression for the primary outcome, chronic pelvic pain severity at 1 year was
      independently associated with a higher score on the Pain Catastrophizing Scale at
      baseline (odds ratio, 1.10; 95% confidence interval, 1.00-1.21, P = .04),
      controlling for baseline pain, treatment effects (surgery), age, and referral
      status. CONCLUSION: Improvements in chronic pelvic pain severity, quality of
      life, and health care utilization were observed in a 1-year cohort in an
      interdisciplinary setting. Higher pain catastrophizing at baseline was associated
      with greater chronic pelvic pain severity at 1 year. Consideration should be
      given to stratifying pelvic pain patients by catastrophizing level (rumination,
      magnification, helplessness) in research studies and in clinical practice.

PMID- 29031894
TI  - Refractory urgency urinary incontinence treatment in women: impact of age on
      outcomes and complications.
AB  - BACKGROUND: Women with refractory urgency urinary incontinence (ie, unresponsive
      to behavioral and pharmacological interventions) are treated with
      onabotulinumtoxinA or sacral neuromodulation. OBJECTIVE: The objective of the
      study was to compare treatment efficacy and adverse events in women <65 and >=65
      years old treated with onabotulinumtoxinA or sacral neuromodulation. STUDY
      DESIGN: This study was a planned secondary analysis of a multicenter, randomized
      trial that enrolled community-dwelling women with refractory urgency urinary
      incontinence to onabotulinumtoxinA or sacral neuromodulation treatments. The
      primary outcome was a change in mean daily urgency urinary incontinence episodes
      on a bladder diary over 6 months. Secondary outcomes included >=75% urgency
      urinary incontinence episode reduction, change in symptom severity/quality of
      life, treatment satisfaction, and treatment-related adverse events. RESULTS: Both
      age groups experienced improvement in mean urgency urinary incontinence episodes
      per day following each treatment. There was no evidence that mean daily urgency
      urinary incontinence episode reduction differed between age groups for
      onabotulinumtoxinA (adjusted coefficient, -0.127, 95% confidence interval, -1.233
      to 0.979; P = .821) or sacral neuromodulation (adjusted coefficient, -0.698, 95%
      confidence interval, -1.832 to 0.437; P = .227). Among those treated with
      onabotulinumtoxinA, women <65 years had 3.3-fold greater odds of >=75% resolution
      than women >=65 years (95% confidence interval, 1.56 -7.02). Women <65 years had
      a greater reduction in Overactive Bladder Questionnaire Short Form symptom bother
      scores compared with women >=65 years by 7.49 points (95% confidence interval, 
      3.23 to -11.74), regardless of treatment group. There was no difference between
      quality of life improvement by age. Women >=65 years had more urinary tract
      infections following onabotulinumtoxinA and sacral neuromodulation (odds ratio,
      1.9, 95% confidence interval, 1.2-3.3). There was no evidence of age differences
      in sacral neuromodulation revision/removal or catheterization following
      onabotulinumtoxinA treatment. CONCLUSION: Younger women experienced greater
      absolute continence, symptom improvement, and fewer urinary tract infections;
      both older and younger women had beneficial urgency urinary incontinence episode
      reduction, similar rates of other treatment adverse events, and improved quality
      of life.

PMID- 29031897
TI  - Smart electrical bi-layers lipopeptides: Novel peptidic chains like zigzag map
      esterified with phospho-glyceride as mono-layer moieties capable in forming a
      meso-sphere- envelop with scaffold- ability to cellular impurities.
AB  - Cell impurities are an emerging nucleating molecular barriers having the
      capability in disordering the metabolic chain reactions of proteolysis,
      glycolysis and lipolysis. Their massive effects induced by copolymer crystal
      growth in compaction with metal and mineral transients are extended as well as in
      damaging DNA and mRNA structure motif and other molecular assembly e.g. histones
      structure unites. Their polycrystalline packing modes, polydispersity and their
      tendency to surface and interface adhesion prompted us in structuring scaffold
      biomaterials enriched with biopeptides, layered by phospho-glycerides ester
      forms. The interface tension of the formed map is flexible and dependent to the
      surface exposure and its collapse modes to the surrounding molecular ligands.
      Thus, the attempts in increasing surface exposure e.g. the viscoelastic of
      structured lipopeptides and types of formed network structures interplays an
      extra- conjugating biomolecules having a least cytotoxicity effects to cells
      constituents. Disulfides molecules are selected to be the key regulatory element
      in rejoining both lipidic and proteic moieties by disordering atoms status via
      chemical ionization using organic catalyst. The insertion of methionine based
      peptidic chain at the lateral surfaces of scaffold biomaterials enhances the
      electron-meta-static motions by raising a molecular disordering status at
      distinct regions of the map e.g. epimerization into a nonpolar side that helps
      the chemical conjunction of disulfide groups with the esterified
      phosphoglycerides mono-layers. These effects in turn are accomplished by the
      formation of meso-sphere nonpolar- vesicles. The oxidation of disulfide group
      would alter the ordering of initial molecules by raising a newly molecular
      disorders to the map with high polarity to surface regions. In the same time
      indicates a continuation in the crystallization growth factor via a low chemical
      lesions between the impurities and a supersaturation in the intra-atomic
      distances with maximum cross linking to the deformed ligand with scaffold
      biomaterials.

PMID- 29031898
TI  - Comparative analysis of ginsenosides in human glucocorticoid receptor binding,
      transactivation, and transrepression.
AB  - Conflicting data exist on the effect of ginsenosides on transactivation of human
      glucocorticoid receptor alpha (herein referred to as glucocorticoid receptor),
      and relatively little is known regarding the effect of these chemicals on
      transrepression of this receptor. We investigated the effect of 20(S)
      protopanaxadiol (PPD), PPD-type ginsenosides (Rb1, Rb2, Rc, Rd, Rh2, and Compound
      K), 20(S)-protopanaxatriol (PPT), and PPT-type ginsenosides (Re, Rf, Rg1, and
      Rh1) on glucocorticoid receptor binding, transactivation, and transrepression.
      Each ginsenoside was less efficacious than dexamethasone (positive control) in
      binding to the ligand-binding domain of glucocorticoid receptor. Among the
      ginsenosides investigated, Rh2 had the smallest IC50 value (15 +/- 1uM), whereas
      it was 0.02 +/- 0.01uM for dexamethasone. In contrast to dexamethasone, none of
      the ginsenosides influenced glucocorticoid receptor transactivation or
      transrepression in LS180 human colorectal adenocarcinoma cells, as assessed in a
      dual-luciferase reporter gene assay. Rh2 did not affect the endogenous mRNA level
      of tyrosine aminotransferase (marker for glucocorticoid receptor transactivation)
      or corticosteroid-binding globulin (marker for glucocorticoid receptor
      transrepression) in HepG2 human hepatocellular carcinoma cells. This chemical
      also did not alter the response by a glucocorticoid receptor agonist
      (dexamethasone or Compound A) in the dual-luciferase reporter gene assay or
      target gene expression assay. In conclusion, ginsenosides were less efficacious
      and less potent than dexamethasone in binding to the ligand-binding domain of
      glucocorticoid receptor. The number of glycosylated groups was associated with a
      decrease in receptor binding potency. PPD-type and PPT-type ginsenosides are not
      modulators of glucocorticoid receptor transactivation or transrepression in LS180
      and HepG2 cells.

PMID- 29031899
TI  - Synapse formation in the brain can be enhanced by co-administering three specific
      nutrients.
AB  - The memory impairments of early Alzheimer's disease [AD] are thought to result
      from a deficiency in synapses within the hippocampus and related brain regions.
      This deficiency could result from an acceleration in synapse turnover - perhaps
      caused by an endogenous neurotoxin like A-beta oligomers - or from a decrease in
      the production of the synaptic membrane needed to form new synapses. An AD
      associated decrease in synaptogenesis almost certainly does occur, inasmuch as
      major decreases are also observed in the numbers of hippocampal dendritic spines,
      the immediate cytologic precursor of glutamatergic synapses. The syntheses of new
      dendritic spines and synapses can, however, be increased by concurrently raising
      brain levels of three circulating nutrients - uridine, omega-3 fatty acids
      docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA), and choline. This
      could provide an additional strategy for restoring synapses and thereby memory.
      The three nutrients are rate-limiting precursors in the Kennedy Cycle, the
      pathway which forms the phosphatides that are the major component of synaptic
      membranes. Uridine also increases the production of synaptic proteins, the other
      major membrane constituent, and the outgrowth of neurites. Hence administering
      the three nutrients accelerates synapse formation. These actions of uridine are
      largely mediated by uridine triphosphate (UTP), which can be released as a
      neurotransmitter from presynaptic terminals and can then activate P2Y2 receptors.
      The UTP in neurons can also be converted to cytidylyl triphosphate, CTP, the
      intermediate utilized in the Kennedy Cycle.

PMID- 29031900
TI  - Resveratrol improved detrusor fibrosis induced by mast cells during progression
      of chronic prostatitis in rats.
AB  - To investigate the detrusor fibrosis and urinary dysfunction in chronic
      prostatitis (CP), and to investigate whether resveratrol can improve the urinary
      dysfunction and the underlying molecular mechanism. After rat model of CP is
      established by subcutaneously injecting DPT vaccine, rats are treated with
      resveratrol. Experiments of bladder pressure and volume test in rats are used to
      investigate the effect of resveratrol on urinary dysfunction in CP rats. To
      assess tissue fibrosis, picrosirius red staining is performed. H&E staining is
      performed to identify the histopathological changes. Western blot and
      immunohistochemical staining are used to examine the expression of c-kit,
      SCF,tryptase, TGF-beta, Wnt and alpha-SMA. The results of bladder pressure and
      volume test show that the maximum capacity of the bladder, residual urine volume
      and maximum voiding are increased significantly in CP rats. CP rats show
      significantly increased collagen deposition in the detrusor. H&E staining show
      that detrusor muscle arranged in disorder with fracture from CP rats. The results
      of western blot and immunohistochemical staining demonstrate that the activity of
      c-kit/SCF and TGF-beta/Wnt/beta-catenin pathway, expression levels of tryptase
      and alpha-SMA in bladder detrusor of CP group are significantly increased
      compared with the control group. However, resveratrol treatment significantly
      improved these factors. mast cell activation induced by the increased expression
      of c-kit/SCF in CP rats, may promote detrusor fibrosis which have a close
      relationship with urinary dysfunction. Resveratrol can improve the dysfunction by
      downregulating the mast cell activation and the activity of TGF-beta/Wnt/beta
      catenin pathway.

PMID- 29031901
TI  - Als and Ftd: Insights into the disease mechanisms and therapeutic targets.
AB  - Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD)
      are neurodegenerative disorders, related by signs of deteriorating motor and
      cognitive functions, and short survival. The causes are still largely unknown and
      no effective treatment currently exists. It has been shown that FTLD may coexist
      with ALS. The overlap between ALS and frontotemporal dementia (FTD), the clinical
      syndrome associated with FTLD, occurs at clinical, genetic, and pathological
      levels. The hallmark proteins of the pathognomonic inclusions are SOD-1, TDP-43
      or FUS, rarely the disease is caused by mutations in the respective genes.
      Frontotemporal lobar degenerations (FTLD) is genetically, neuropathologically and
      clinically heterogeneous and may present with behavioural, language and
      occasionally motor disorder, respectively. Almost all cases of ALS, as well as
      tau-negative FTLD share a common neuropathology, neuronal and glial inclusion
      bodies containing abnormal TDP-43 protein, collectively called TDP-43
      proteinopathy. Recent discoveries in genetics (e.g. C9orf72 hexanucleotide
      expansion) and the subsequent neuropathological characterization have revealed
      remarkable overlap between ALS and FTLD-TDP indicating common pathways in
      pathogenesis. For ALS, an anti-glutamate agent riluzole may be offered to slow
      disease progression (Level A), and a promising molecule, arimoclomol, is
      currently in clinical trials. Other compounds, however, are being trailed and
      some have shown encouraging results. As new therapeutic approaches continue to
      emerge by targeting SOD1, TDP-43, or GRN, we present some advances that are being
      made in our understanding of the molecular mechanisms of these diseases, which
      together with gene and stem cell therapies may translate into new treatment
      options.

PMID- 29031902
TI  - Chrysophanol inhibits endoplasmic reticulum stress in cerebral ischemia and
      reperfusion mice.
AB  - Endoplasmic reticulum (ER) stress plays a critical role in mediating
      ischemia/reperfusion (I/R) damage in the brain. Our previous study showed that
      Chrysophanol (CHR) alleviated cerebral ischemic injury in mice and nuclear factor
      kappaB (NF-kappaB) involved in its neuroprotective effect, but the precise
      mechanism remains not fully understood. The present study investigated the effect
      of CHR treatment on I/R-induced ER stress. Mice were subjected to middle cerebral
      artery occlusion (MCAO) for 45min and received either vehicle or CHR (0.1mg/kg)
      for 14 days after reperfusion. Terminal deoxynucleotidyl transferase (TdT)
      mediated dUTP nick end labeling (TUNEL) was used to detect apoptotic cells in
      penumbral tissue. The expression of ER stress-related factors including glucose
      regulated protein 78 (GRP78), phosphorylated eukaryotic initiation factor 2alpha
      (p-eIF2alpha), CCAAT-enhancer-binding protein homologous protein (CHOP), and
      caspase-12 as well as inhibitory kappaB-alpha (IkappaB-alpha), the inhibitor of
      NF-kappaB, was assessed. Our results demonstrated that CHR treatment reduced MCAO
      induced upregulation of GRP78, p-eIF2alpha, CHOP, and caspase-12 in the ischemic
      brain. Moreover, the TUNEL-positive neuronal cells, which were colocalized with
      CHOP and caspase-12, decreased in response to CHR treatment, indicating that CHR
      protects against I/R injury by inhibiting ER stress-associated neuronal
      apoptosis. In addition, CHR reversed the decrease in IkappaB-alpha level induced
      by MCAO, which was attributed at least in part to the attenuation of
      translational inhibition induced by eIF2alpha phosphorylation, indicating that
      CHR exerts anti-inflammatory effects following I/R by inhibiting ER stress
      response. These results suggest that attenuation of ER stress may be involved in
      the mechanisms of neuroprotective effects of CHR.

PMID- 29031903
TI  - Agmatine inhibits chronic morphine exposure-induced impairment of hippocampal
      neural progenitor proliferation in adult rats.
AB  - Our previous studies have shown that agmatine inhibited opioid dependence, yet
      the neural mechanism remains unclear. Growing evidence showed that opioids
      decrease neurogenesis in the adult hippocampal subgranular zone by inhibiting
      neural progenitor proliferation. However, whether agmatine affects chronic opioid
      exposure-induced impairment to hippocampal neural progenitor cell proliferation
      remains unknown. In the present study, we investigated the role of agmatine in
      hippocampal neural progenitors in morphine dependence rats. We found that chronic
      administration of morphine for 12 days induced morphine dependence in rats. This
      treatment not only decreased the proliferation of hippocampal neural progenitors
      in the granule cell layer, but also decreased the levels of hippocampal cAMP,
      pCREB and BDNF. However, these alterations can be restored to normal levels by co
      treatment of agmatine (10mg/kg, s.c.). In vitro treatment with agmatine (10uM)
      for two days significantly increased proliferation of the cultured hippocampal
      neural progenitors. Concurrent treatment of agmatine (10uM) with morphine (10 or
      50uM) reversed the supression of morphine-induced neural progenitor
      proliferation. In conclusion, we found that agmatine abolished chronic morphine
      induced decrease in proliferation of hippocampal progenitors in vivo and in
      vitro, which may be due to the increase in cAMP-CREB-BDNF signaling. The
      enhancement of agmatine to proliferation of hippocampal progenitors may be one of
      the important mechanisms involved in the inhibition of morphine dependence by
      agmatine.

PMID- 29031904
TI  - Definitive radiotherapy for a head and neck Merkel cell carcinoma and
      comprehensive nodal volumes: a case for using a computer-designed variable
      thickness compensator to reduce risk and severity of mucositis.
AB  - When contemplating how to treat head and neck primary cancers and regional lymph
      nodes with radiotherapy, we often select the contemporary intensity-modulated
      radiotherapy (IMRT) without much consideration of older methods that may give
      fewer side effects and be more cost-effective. For an 87-year-old female with a
      1.5-cm Merkel cell carcinoma (MCC) located 1.5 cm lateral to the orbital rim, we
      were challenged to deliver 50 Gy to comprehensive elective nodal regions and 70
      Gy to the primary. We were particularly concerned about the potential adverse
      acute effects of radiotherapy to mucosal structures in this elderly female. Acute
      mucositis could impair nutrition, quality of life, and treatment intensity
      especially given her age. We compared 3 techniques that are appropriate for this
      target: step-and-shoot IMRT, matched electron fields (MEF), and electron
      conformal therapy (BolusECTTM). We selected and treated her with BolusECTTM
      because of better sparing of larynx, pharynx, oral cavity and lips, and shortest
      treatment time. This is a reasonable option for treating ipsilateral head and
      neck target volumes at centers where only these 3 techniques are available.

PMID- 29031906
TI  - Suckling induced insulin-like growth factor-1 (IGF-1) release in mother rats.
AB  - OBJECTIVE: Lactation involves significant neuroendocrine changes. The elevated
      prolactin (PRL) release from the pituitary, induced markedly by suckling, is the
      most relevant example. Suckling also causes a significant and rapid elevation in
      growth hormone (GH) levels. GH is necessary for milk synthesis as milk yield is
      stopped completely in the absence of PRL and GH, while the absence of PRL alone
      causes only a 50% reduction. Insulin-like growth factor-1 (IGF-1) plays an
      important role in the GH axis. GH exerts its effects through IGF-1 in the
      periphery, for example in the mammary gland. In addition, IGF-1 is responsible
      for the long-loop feedback control of GH secretion. DESIGN: IGF-1 secretion has
      not been established yet in mothers. Therefore, in the present study, we
      investigated the effect of suckling on serum IGF-1 level in rat mothers and
      correlated it with serum PRL levels. We examined a potential mechanism of the
      regulation of IGF-1 level during suckling by administering IGF-1 into the lateral
      ventricle of rat mothers continuously for 12days, or acutely, right before the
      start of suckling. RESULTS: We described that suckling affected IGF-1 release
      based on one-way repeated measures ANOVA (F=10.8 and p<0.001) and caused a marked
      increase of IGF-1 level 30min after the start of suckling (p<0.001). We
      demonstrated a significant (p<0.05; the correlation coefficient was 0.29)
      correlation to PRL level during suckling which supports that PRL could induce IGF
      1 release. The prolonged central IGF-1 administration diminished the suckling
      induced IGF-1 surge (F=9.19 and p<0.001) while the acute treatment did not have
      any effect compared to artificial cerebrospinal fluid injection, analysed with
      two-way repeated measures ANOVA. CONCLUSIONS: In conclusion, suckling induces IGF
      1 release either by elevating PRL or GH. Long-loop feedback via IGF-1 in the GH
      axis can diminish this action.

PMID- 29031907
TI  - About cytokeratin 19 and the drivers of liver regeneration.

PMID- 29031905
TI  - Fibroblast growth factor 21 decreases after liver fat reduction via growth
      hormone augmentation.
AB  - OBJECTIVE: Fibroblast growth factor 21 (FGF21) ameliorates steatohepatitis but is
      increased in humans with fatty liver, potentially due to compensatory mechanisms
      and/or FGF21 resistance. Further, animal models suggest that GH increases serum
      FGF21. Tesamorelin, a growth hormone releasing hormone agonist, reduces liver fat
      in HIV-infected individuals. The objectives of this study were to investigate
      changes in FGF21 during tesamorelin treatment, to elucide the interplay between
      FGF21, GH augmentation, and liver fat reduction in humans. METHODS: 50 HIV
      infected men and women with increased abdominal adiposity participated in this
      randomized, placebo-controlled trial of tesamorelin, 2mg vs. identical placebo
      daily for six months. Fasting laboratory measures, liver fat by 1H-magnetic
      resonance spectroscopy, and visceral adipose tissue (VAT) by computed tomography
      were obtained. Euglycemic hyperinsulinemic clamp was performed in a randomly
      selected subset. RESULTS: At baseline, serum log10 FGF21 was significantly
      associated with log10 liver fat (r=0.32, p=0.03). Log10 FGF21 tended to decrease
      in the tesamorelin group compared to placebo (p=0.06). Among the entire cohort,
      reductions in FGF21 were significantly associated with reductions in liver fat
      (rho=0.41, p=0.01), log10 gamma glutamyl tran speptidase (GGT, r=0.40, p=0.009),
      and FIB4 index (r=0.37, p=0.02). CONCLUSIONS: In HIV-infected individuals, FGF21
      is significantly positively associated with liver fat. FGF21 decreases in
      association with reductions in liver fat, GGT, and FIB4, suggesting that FGF21 is
      upregulated in the context of steatosis and steatohepatitis and is reduced when
      these conditions improve. Moreover, these data suggest that tesamorelin improves
      liver fat via pathways other than increasing serum FGF21. TRIAL REGISTRATION:
      clinicaltrials.govNCT01263717.

PMID- 29031908
TI  - Intrauterine air impairs embryonic postimplantation development in mice.
AB  - OBJECTIVE: Although most embryologists load air bubbles into the catheter along
      with embryos during embryo transfer, the effects of these air bubbles on embryo
      transfer success rate are not clear. STUDY DESIGN: Air bubbles were nonsurgically
      injected into unilateral uterine horns of mice to demonstrate the negative
      effects of intrauterine air bubbles on embryonic development. RESULTS: Our data
      showed that when air bubbles are nonsurgically injected into unilateral uterine
      horns of pregnant 4days mice the litter size is significantly decreased. Four
      days after the introduction of air, abnormal decidua and dead conceptuses were
      detected in the uterine horns receiving the air bubbles. In addition,
      intrauterine air also significantly impaired murine embryo transfer success
      rates, and induced an increase in endometrial capillary permeability and
      decidualization in mice on day 4 of pseudopregnancy. These results strongly
      indicated that the air bubbles loaded into embryo transfer catheters to bracket
      the embryo-containing medium may have negative effect on embryonic implantation
      and development. CONCLUSIONS: Intrauterine air impaired murine embryonic
      postimplantation development, and this provided some clues for improving embryo
      transfer techniques in human.

PMID- 29031909
TI  - The retromer subunit Vps26 mediates Notch signaling during Drosophila oogenesis.
AB  - During endocytosis, molecules are internalized by the cell through the
      invagination of the plasma membrane. Endocytosis is required for proper cell
      function and for normal development in Drosophila. One component of the endocytic
      pathway is the retromer complex, which recycles transmembrane proteins to other
      parts of the cell such as the plasma membrane and the trans-Golgi network.
      Previous studies have shown that mutations to the retromer complex result in
      developmental defects in Drosophila. In humans, retromer dysfunction has been
      implicated in Alzheimer's and Parkinson's disease, but little is known about the
      role of the retromer complex in Drosophila oogenesis. In the current project, we
      examined the role of the retromer protein Vps26 in oogenesis by characterizing
      the phenotype of vps26 germline clones. Immunofluorescence was used to visualize
      the expression of membrane proteins and vesicular trafficking markers in mutant
      egg chambers. We find that vps26 germline clones exhibit a signaling defect
      between the germline cells and follicle cells indicated by an increase in
      LysoTracker staining of the border cells in the mutants. We show that this
      signaling defect in vps26 mutants may be the result of impaired Notch signaling
      based on the misexpression of multiple proteins in the Notch signaling pathway in
      vps26 mutants.

PMID- 29031910
TI  - Scanning distortion correction in STEM images.
AB  - Various disturbances do exist in the image taking process of scanning
      transmission electron microscopes (STEM), which seriously reduces the resolution
      and accuracy of STEM images. In this paper, a deep understanding of the scanning
      distortion influence on the real and reciprocal spaces of STEM images is achieved
      via theoretical modeling and simulation. A scanning distortion correction
      algorithm is further developed based on two images scanned along perpendicular
      directions, which is able to effectively correct scanning distortion induced
      deviations and significantly increase the signal to noise ratio of STEM images.

PMID- 29031911
TI  - Gene polymorphisms of DISC1 is associated with schizophrenia: Evidence from a
      meta-analysis.
AB  - BACKGROUND: Previous studies suggest an association between Disrupted in
      schizophrenia 1 (DISC1) polymorphisms and schizophrenia (SCZ). However, the
      available data are often inconsistent, regarding the difference in sample size,
      ethnicity, genotyping method, etc. Thus, we carried out a meta-analysis to
      determine whether DISC1 polymorphisms contributed susceptibility to SCZ. METHODS:
      A methodical literature review was operated using the English and Chinese core
      electronic databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were
      applied to determine the correlation between DISC1 gene polymorphisms and SCZ
      susceptibility. Subgroup analyses were carried out by stratification of
      ethnicity. P values were Bonferroni adjusted to account for multiple testing.
      Publication bias was evaluated by funnel plots, Egger's test and the trim and
      fill method. RESULTS: Meta-analyses results suggested that DISC1 polymorphisms
      (rs821616 and rs821597) increased SCZ risk in overall populations. In subgroups
      of ethnicity, DISC1 polymorphisms (rs821616 and rs821597) was associated with
      susceptibility to SCZ among the Chinese population (for rs821616: TT+AT vs. AA:
      OR=1.338, 95% CI=1.124-1.592, P=0.001; T vs. A: OR=1.300, 95% CI=1.124-1.504,
      P<0.000; for rs821597: AA+AG vs. GG: OR=1.508, 95% CI=1.268-1.794, P<0.001; A vs.
      G: OR=1.345, 95% CI=1.184-1.527, P<0.001). A positive correlation was also
      observed between the single marker rs821616 and SCZ among the Japanese population
      in the recessive model (TT vs. AT+AA: OR=1.524, 95% CI=1.185-1.959, P=0.001).
      There was no significant relationship between other DISC1 polymorphisms
      (rs3738401, rs2273890, rs3738398, rs3738402, rs2492367, rs843979, rs3737597,
      rs4658971, rs1538979, rs1000731 and rs3738399) and SCZ. CONCLUSIONS: DISC1
      polymorphisms increased a risk of SCZ, especially in the Chinese population. In
      order to further corroborate our findings, large well-designed epidemiological
      studies are needed.

PMID- 29031912
TI  - The association of beta-arrestin2 polymorphisms with response to antidepressant
      treatment in depressed patients.
AB  - The study of genetic polymorphisms involved in antidepressants (AD) response is
      essential to provide a personalized medicine approach in the field of depression.
      beta-arrestin 2 (ARRB2) is a candidate gene in the pharmacogenetics of AD as it
      is involved in the signaling cascade downstream of numerous neurotransmitter
      receptors. We investigated the association between five ARRB2 single nucleotide
      polymorphisms (SNPs): rs1045280, rs2036657, rs4790694, rs3786047 and rs452246,
      and response to AD treatment in a sample of 569 patients with a major depressive
      episode treated for 6months. We show that GG/GT patients for rs4522461 (n=534)
      and AA/AC patients for rs4790694 (n=244) have a lower response to AD than other
      genotype groups (HDRS score of 10.9 vs 8.0 after 6months, multivariate analysis:
      p=0.03; 12.2 vs 9.6, p=0.02, respectively). These data provide additional
      evidence that beta-arrestin 2 is a regulator of intracellular signal transduction
      processes involved in AD treatment.

PMID- 29031913
TI  - Chronic pain and pain processing in Parkinson's disease.
AB  - Pain is experienced by the vast majority of patients living with Parkinson's
      disease. It is most often of nociceptive origin, but may also be ascribed to
      neuropathic (radicular or central) or miscellaneous sources. The recently
      validated King's Parkinson's Disease Pain Scale is based on 7 domains including
      musculoskeletal pain, chronic body pain (central or visceral), fluctuation
      related pain, nocturnal pain, oro-facial pain, pain with
      discolouration/oedema/swelling, and radicular pain. The basal ganglia integrate
      incoming nociceptive information and contribute to coordinated motor responses in
      pain avoidance and nocifensive behaviors. In Parkinson's disease, nigral and
      extra-nigral pathology, involving cortical areas, brainstem nuclei, and spinal
      cord, may contribute to abnormal central nociceptive processing in patients
      experiencing pain or not. The dopamine deficit lowers multimodal pain thresholds
      that are amenable to correction following levodopa dosing. Functional brain
      imaging with positron emission tomography following administration of H215O
      revealed abnormalities in the sensory discriminative processing of pain
      (insula/SII), as well as in the affective motivational processing of pain
      (anterior cingulate cortex, prefrontal cortex). Pain management is dependent on
      efforts invested in diagnostic accuracy to distinguish nociceptive from
      neuropathic pain. Treatment requires an integrated approach including strategies
      to lessen levodopa-related response fluctuations, in addition to other
      pharmacological and non-pharmacological options such as deep brain stimulation
      and rehabilitation.

PMID- 29031914
TI  - Population Health and Tailored Medical Care in the Home: the Roles of Home-Based
      Primary Care and Home-Based Palliative Care.
AB  - With the growth of value-based care, payers and health systems have begun to
      appreciate the need to provide enhanced services to homebound adults. Recent
      studies have shown that home-based medical services for this high-cost, high-need
      population reduce costs and improve outcomes. Home-based medical care services
      have two flavors that are related to historical context and specialty background
      home-based primary care (HBPC) and home-based palliative care (HBPalC). Although
      the type of services provided by HBPC and HBPalC (together termed "home-based
      medical care") overlap, HBPC tends to encompass longitudinal and preventive care,
      while HBPalC often provides services for shorter durations focused more on
      distress management and goals of care clarification. Given workforce constraints
      and growing demand, both HBPC and HBPalC will benefit from working together
      within a population health framework-where HBPC provides care to all patients who
      have trouble accessing traditional office practices and where HBPalC offers
      adjunctive care to patients with high symptom burden and those who need
      assistance with goals clarification. Policy changes that support provision of
      medical care in the home, population health strategies that tailor home-based
      medical care to the specific needs of the patients and their caregivers, and
      educational initiatives to assure basic palliative care competence for all home
      based medical providers will improve access and reduce illness burden to this
      important and underrecognized population.

PMID- 29031915
TI  - Experimental and Monte Carlo-based determination of the beam quality specifier
      for TomoTherapyHD treatment units.
AB  - Reference dosimetry by means of clinical linear accelerators in high-energy
      photon fields requires the determination of the beam quality specifier TPR20,10,
      which characterizes the relative particle flux density of the photon beam. The
      measurement of TPR20,10 has to be performed in homogenous photon beams of size
      10*10cm2 with a focus-detector distance of 100cm. These requirements cannot be
      fulfilled by TomoTherapy treatment units from Accuray. The TomoTherapy unit
      provides a flattening-filter-free photon fan beam with a maximum field width of
      40cm and field lengths of 1.0cm, 2.5cm and 5.0cm at a focus-isocenter distance of
      85cm. For the determination of the beam quality specifier from measurements under
      nonstandard reference conditions Sauer and Palmans proposed experiment-based fit
      functions. Moreover, Sauer recommends considering the impact of the flattening
      filter-free beam on the measured data. To verify these fit functions, in the
      present study a Monte Carlo based model of the treatment head of a TomoTherapyHD
      unit was designed and commissioned with existing beam data of our clinical
      TomoTherapy machine. Depth dose curves and dose profiles were in agreement within
      1.5% between experimental and Monte Carlo-based data. Based on the fit functions
      from Sauer and Palmans the beam quality specifier TPR20,10 was determined from
      field sizes 5*5cm2, 10*5cm2, 20*5cm2 and 40*5cm2 based on dosimetric measurements
      and Monte Carlo simulations. The mean value from all experimental values of
      TPR20,10 resulted in TPR20,10-=0.635+/-0.4%. The impact of the non-homogenous
      field due to the flattening-filter-free beam was negligible for field sizes below
      20*5cm2. The beam quality specifier calculated by Monte Carlo simulations was
      TPR20,10=0.628 and TPR20,10=0.631 for two different calculation methods. The
      stopping power ratio water-to-air sw,aDelta directly depends on the beam quality
      specifier. The value determined from all experimental TPR20,10 data was
      sw,aDelta=1.126+/-0.1%, which is in excellent agreement with the value directly
      calculated by Monte Carlo simulations. The agreement is a good indication that
      the equations proposed by Sauer and Palmans are able to calculate the beam
      quality specifier under reference conditions from measurements in arbitrary
      photon field sizes with high accuracy and are applicable for the TomoTherapyHD
      treatment unit.

PMID- 29031916
TI  - Image guided adaptive external beam radiation therapy for cervix cancer:
      Evaluation of a clinically implemented plan-of-the-day technique.
AB  - BACKGROUND: Radiotherapy for cervix cancer is challenging in patients exhibiting
      large daily changes in the pelvic anatomy, therefore adaptive treatments (ART)
      have been proposed. The aim of this study was the clinical implementation and
      subsequent evaluation of plan-of-the-day (POTD)-ART for cervix cancer in supine
      positioning. The described workflow was based on standard commercial equipment
      and current quality assurance (QA) methods. MATERIALS AND METHODS: A POTD
      strategy, which employs a VMAT plan library consisting of an empty bladder plan,
      a full bladder plan and a motion robust backup plan, was developed. Daily
      adaption was guided by cone beam computed tomography (CBCT) imaging after which
      the best plan from the library was selected. Sixteen patients were recruited in a
      clinical study on ART, for nine POTD was applied due to their large organ motion
      derived from two computed tomography (CT) scans with variable bladder filling.
      All patients were treated to 45Gy in 25 fractions. Plan selection frequencies
      over the treatment course were analyzed. Daily doses in the rectum, bladder and
      cervix-uterus target (CTV-T) were derived and compared to a simulated non-adapted
      treatment (non-ART), which employed the robust plan for each fraction.
      Additionally, the adaption consistency was determined by repeating the plan
      selection procedure one month after treatment by a group of experts. ART-specific
      QA methods are presented. RESULTS: 225 ART fractions with CBCTs were analyzed.
      The empty bladder plan was delivered in 49% of the fractions in the first
      treatment week and this number increased to 78% in the fifth week. The daily
      coverage of the CTV-T was equivalent between ART and the non-ART simulation,
      while the daily total irradiated volume V42.75Gy (95% of prescription dose) was
      reduced by a median of 87cm3. The median delivered V42.75Gy was 1782cm3. Daily
      delivered doses (V42.75Gy, V40Gy, V30G) to the organs at risk were statistically
      significantly reduced by ART, with a median difference in daily V42.75Gy in
      rectum and bladder of 3.2% and 1.1%, respectively. The daily bladder V42.75Gy and
      V40Gy were decreased by more than 10 percent points in 30% and 24% of all
      fractions, respectively, through ART. The agreement between delivered plans and
      retrospective expert-group plan selections was 84%. CONCLUSION: A POTD-ART
      technique for cervix cancer was successfully and safely implemented in the clinic
      and evaluated. Improved normal tissue sparing compared to a simulated non-ART
      treatment could be demonstrated. Future developments should focus on commercial
      automated software solutions to allow for a more widespread adoption and to keep
      the increased workload manageable.

PMID- 29031917
TI  - How Good Were Candidate Gene Guesses in Schizophrenia Genetics?

PMID- 29031918
TI  - Polygenic Risk Scores in Psychiatry.

PMID- 29031919
TI  - Parsing Anatomical Dysconnectivity in Psychosis.

PMID- 29031920
TI  - Kraepelin's Crumbling Twin Pillars: Using Biology to Reconstruct Psychiatric
      Nosology From the Bottom Up.

PMID- 29031921
TI  - Disconnectionism in Biological Psychiatry.

PMID- 29031922
TI  - Catechin loaded PLGA submicron-sized fibers reduce levels of reactive oxygen
      species induced by MWCNT in vitro.
AB  - Reactive oxygen species (ROS) are common products of normal aerobic cellular
      metabolism, but high levels of ROS lead to oxidative stress and cellular damage.
      Therefore, effective antioxidant therapies are needed to prevent ROS
      overproduction. This study reports the development of poly(l-lactide-co
      glycolide) (PLGA) bicomponent fibers loaded with selected amounts of the natural
      polyphenolic antioxidant catechin. Thereby a novel route based on emulsion
      electrospinning is investigated to obtain tailored and sustained release rates
      for chatechin. The activity of the released catechin was assessed for its
      influence on multi-walled carbon nanotube (MWCNT) induced formation of reactive
      oxygen species (ROS) in the human alveolar epithelial the cell line A549.
      Homogenous fiber morphologies were obtained at specified ranges of PLGA
      concentrations within the emulsions including the formation of a core - sheath
      structure localizing the drug within the fiber core. In vitro measurements of the
      delivery showed moderate burst release kinetics in a first phase followed by a
      linear and smooth release at long term. In combination with polymer degradation
      studies a mostly diffusion controlled release mechanism was revealed exhibiting
      only marginal degradation of the polymer during the time span of the drug
      delivery. As a proof of concept, the activity of released catechin in A549 cells
      stimulated with MWCNTs was determined and revealed a high reduction of ROS
      production in a dose dependent manner. This effect diminishes over time
      indicating a depletion of catechin.

PMID- 29031923
TI  - DEAE-Dextran coated paclitaxel nanoparticles act as multifunctional nano system
      for intranuclear delivery to triple negative breast cancer through VEGF and
      NOTCH1 inhibition.
AB  - Triple negative breast cancer revolution has identified a plethora of therapeutic
      targets making it apparent that a single target for its treatment could be rare
      hence creating an urge to develop robust technologies for combination drug
      therapy. Paclitaxel, hailed as the most significant advancement in chemotherapy
      faces several underpinnings due to its low solubility and permeability. Advancing
      research has demonstrated the role of interferons in cancer. DEAE-Dextran, an
      emerging molecule with evidence of interferon induction was utilized in the
      present study to develop a nanoformulation in conjugation with paclitaxel to
      target multiple therapeutic pathways, with diminution of paclitaxel adverse
      effects and develop a specific targeted nano system. Evidently, it was
      demonstrated that DEAE-Dextran coated nanoformulation portrays significant
      synergistic cytotoxicity in the various cell lines. Moreover, overcoming the
      activation of ROS by paclitaxel, the combination drug therapy more effectively
      inhibited ROS through beta-interferon induction. The nanoformulation was further
      conjugated to FITC for internalization studies which subsequently indicated
      maximum cellular uptake at 60min post treatment demonstrated by green
      fluorescence from FITC lighting up the nuclear membrane. Precisely, the
      mechanistic approach of nuclear-targeted nanoformulation was evaluated by in vivo
      xenograft studies which showed a synergistic release of beta-interferon at the
      target organ. Moreover, the combination nanoformulation inculcated multiple
      mechanistic approaches through VEGF and NOTCH1 inhibition along with dual beta
      and gamma-interferon overexpression. Overall, the combination therapy may be a
      promising multifunctional nanomaterial for intranuclear drug delivery in TNBC.

PMID- 29031924
TI  - Evaluation of cervical mucus and reproductive efficiency of seasonally anovular
      dairy goats after short-term progestagen-based estrous induction protocols with
      different gonadotropins.
AB  - The use of three different gonadotropins was tested for estrous induction in
      dairy goats during the non-breeding season. All does received an injection of 30
      MUg of d-cloprostenol and intravaginal sponges containing 60mg of
      medroxyprogesterone acetate (MAP) for 6 d plus 20 IU of porcine FSH (pFSH), 200
      IU of eCG or 250 IU of hCG 24h before sponge removal. In Experiment 1 (n=24),
      ovarian ultrasound parameters were recorded and cervical mucus was evaluated
      daily for 5 d after sponge removal or until ovulation. In Experiment 2 (n=80),
      reproductive efficiency of artificially inseminated or naturally mated does was
      assessed. The mean interval from sponge removal to ovulation (73.5+/-23.7 h),
      number of ovulations (1.6+/-0.7) and ovulatory follicle diameter (7.2+/-0.8 mm)
      did not vary (P >0.05) among the three groups. At ovulation, cervical mucus had
      crystalline-striated to striated (22.2%), striated to striated-caseous (72.2%)
      and striated-caseous to caseous (5.6%) appearance. The largest follicle diameter
      was greater (P <0.05) in does with crystalline (6.7+/-1.4 mm), crystalline
      striated (7.2+/-1.1 mm) or striated (7.3+/-1.3 mm) mucus than in those with
      striated-caseous (5.3+/-1.4 mm) or caseous (4.5+/-1.1 mm) mucus. Percentage of
      animals exhibiting estrus (92.5%) and conception rate (60.8%) were similar (P
      >0.05) among the three gonadotropins groups. Results of this study support the
      use of eCG (200 IU), hCG (250 IU) and pFSH (20 IU) for the estrous induction
      protocols in dairy goats during the non-breeding season. Cervical mucus
      evaluation can be used as an additional method to determine the optimal time for
      artificial insemination in goats.

PMID- 29031925
TI  - Attributes of excellent surgical trainers: An analysis of outstanding trainers.
AB  - Excellent surgical trainers play a key role in teaching, mentoring and inspiring
      the next generation of trainee surgeons. Although there are differences in
      approach, personality and technique among trainers, common themes exist for those
      that truly shine as examples of good training. The good surgical trainer has long
      been the "unsung hero" of patient safety, inspiring and imparting wisdom and
      skill in trainee surgeons, and instilling a sense of confidence and compassion.
      In order to recognise exceptional trainers, the Association of Surgeons in
      Training (ASiT) introduced the Silver Scalpel Award in 2000. The award
      acknowledges talented trainers who go the "extra mile" for their trainees, and
      the selection process includes both written nominations and structured interviews
      with the nominees. We wished to identify what makes the best trainers excellent,
      to see if these attributes could be used to develop recommendations on how to
      train and how to support trainers. Here we present an outline of key attributes
      of an excellent surgical trainer, based on qualitative synthesis of the interview
      sheets from Silver Scalpel interviews. These results clearly highlight that good
      trainers are first and foremost good doctors, and that good training goes hand-in
      hand with excellent patient care. This symbiotic relationship between training
      and patient outcomes should be acknowledged, and trainers should be supported by
      their employers to empower them to carry out their dual roles of training and
      patient care to the best of their ability. Trainers are key role models to
      inspire the next generation of surgeons and exceptional trainers should be
      celebrated.

PMID- 29031926
TI  - Monitoring driver fatigue using a single-channel electroencephalographic device:
      A validation study by gaze-based, driving performance, and subjective data.
AB  - Driver fatigue can impair performance as much as alcohol does. It is the most
      important road safety concern, causing thousands of accidents and fatalities
      every year. Thanks to technological developments, wearable, single-channel EEG
      devices are now getting considerable attention as fatigue monitors, as they could
      help drivers to assess their own levels of fatigue and, therefore, prevent the
      deterioration of performance. However, the few studies that have used single
      channel EEG devices to investigate the physiological effects of driver fatigue
      have had inconsistent results, and the question of whether we can monitor driver
      fatigue reliably with these EEG devices remains open. Here, we assessed the
      validity of a single-channel EEG device (TGAM-based chip) to monitor changes in
      mental state (from alertness to fatigue). Fifteen drivers performed a 2-h
      simulated driving task while we recorded, simultaneously, their prefrontal brain
      activity and saccadic velocity. We used saccadic velocity as the reference index
      of fatigue. We also collected subjective ratings of alertness and fatigue, as
      well as driving performance. We found that the power spectra of the delta EEG
      band showed an inverted U-shaped quadratic trend (EEG power spectra increased for
      the first hour and half, and decreased during the last thirty minutes), while the
      power spectra of the beta band linearly increased as the driving session
      progressed. Coherently, saccadic velocity linearly decreased and speeding time
      increased, suggesting a clear effect of fatigue. Subjective data corroborated
      these conclusions. Overall, our results suggest that the TGAM-based chip EEG
      device is able to detect changes in mental state while performing a complex and
      dynamic everyday task as driving.

PMID- 29031927
TI  - Particle radiotherapy, a novel external radiation therapy, versus liver resection
      for hepatocellular carcinoma accompanied with inferior vena cava tumor thrombus:
      A matched-pair analysis.
AB  - BACKGROUND: Hepatocellular carcinoma accompanied with inferior vena cava tumor
      thrombus carries a dismal prognosis, and the feasibility of local treatment has
      remained controversial. The present study aimed to compare the outcomes of
      particle radiotherapy and liver resection in patients with hepatocellular
      carcinoma with inferior vena cava tumor thrombus. METHODS: Thirty-one and 19
      patients, respectively, underwent particle radiotherapy and liver resection for
      hepatocellular carcinoma with inferior vena cava tumor thrombus. A matched-pair
      analysis was undertaken to compare the short- and long-term outcomes according to
      tumor stage determined using the tumor-node-metastasis classification. RESULTS:
      Both stages IIIB and IV (IVA and IVB) patients were well-matched for 12 factors,
      including treatment policy and patient and tumor characteristics. The median
      survival time of matched patients with stage IIIB tumors in the particle
      radiotherapy group was greater than that in the liver resection group (748 vs 272
      days, P = .029), whereas no significant difference was observed in the median
      survival times of patients with stage IV tumors (239 vs 311 days, respectively).
      There were significantly fewer treatment-related complications of grade 3 or
      greater in the particle radiotherapy group (0%) than in the liver resection group
      (26%). CONCLUSION: Particle radiotherapy is potentially preferable in
      hepatocellular carcinoma patients with stage IIIB inferior vena cava tumor
      thrombus and at least equal in efficiency to liver resection in those with stage
      IV disease, while causing significantly fewer complications. Considering the
      relatively high survival and low invasiveness of particle radiotherapy when
      compared to liver resection, this approach may represent a novel treatment
      modality for hepatocellular carcinoma with inferior vena cava tumor thrombus.

PMID- 29031928
TI  - The role of purified Clostridium difficile glucosylating toxins in disease
      pathogenesis utilizing a murine cecum injection model.
AB  - Most pathogenic Clostridium difficile produce two major exotoxins TcdA and TcdB,
      in the absence of which the bacterium is non-pathogenic. While it is important to
      investigate the role of each toxin in the pathogenesis of C. difficile infection
      (CDI) using isogenic strains, it is impossible to precisely control the
      expression levels of individual toxins and exclude bacterial factors that may
      contribute to the toxins' effects during infection. In this study, we utilized an
      acute intestinal disease model by injecting purified toxins directly into mouse
      cecum after a midline laparotomy. We evaluated the physical condition of mice by
      clinical score and survival, and the intestinal tissue damage and inflammation by
      histology. Depending on the dose of the toxins, mice developed mild to severe
      colitis, experienced diarrhea or rapidly died. We found that both purified TcdA
      and TcdB were able to induce clinical disease, intestinal inflammation, and
      tissue damage that resembled CDI. TcdA was significantly faster in inducing
      intestinal inflammation and tissue damage, and was approximately five times more
      potent than TcdB in terms of inducing severe gut disease and death outcomes in
      mice. Moreover, we found that the two toxins had significant synergistic effects
      on disease induction. Comparison of the in vivo toxicity of TcdB from clinical
      strains revealed that TcdB from an epidemic RT 027 strain was more toxic than the
      others. Our study thus demonstrates that both TcdA and TcdB, independent of other
      factors from C. difficile bacterium, are able to cause disease that resembles CDI
      and highlights the importance of targeting both toxins for vaccines and
      therapeutics against the disease.

PMID- 29031929
TI  - Permanent His-bundle pacing as an alternative to biventricular pacing for cardiac
      resynchronization therapy: A multicenter experience.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) using biventricular pacing
      (BVP) is effective in patients with heart failure, bundle branch block (BBB), or
      right ventricular pacing. Permanent His-bundle pacing (HBP) has been reported as
      an alternative option for CRT. OBJECTIVE: The purpose of this study was to assess
      the feasibility and outcomes of HBP in CRT eligible or failed patients. METHODS:
      HBP was attempted as a rescue strategy in patients with failed left ventricular
      lead or nonresponse to BVP (group I), or as a primary strategy in patients with
      AV block, BBB, or high ventricular pacing burden as an alternative to BVP (group
      II) in patients with indications for CRT. Implant characteristics, New York Heart
      Association functional class, and echocardiographic data were assessed in follow
      up. RESULTS: HBP was successful in 95 of 106 patients (90%): 30 in group I and 65
      in group II. Mean age was 71 +/- 12 years and 30% were female, with BBB in 45%,
      paced rhythm in 39%, and AV block in 16%. His capture and BBB correction
      thresholds were 1.4 +/- 0.9 V and 2.0 +/- 1.2 V at 1 ms, respectively. During
      mean follow-up of 14 months, both groups demonstrated significant narrowing of
      QRS from 157 +/- 33 ms to 117 +/- 18 ms (P = .0001), increase in left ventricular
      ejection fraction from 30% +/- 10% to 43% +/- 13% (P = .0001), and improvement in
      New York Heart Association functional class from 2.8 +/- 0.5 to 1.8 +/- 0.6 (P =
      .0001) with HBP. Lead-related complications occurred in 7 patients. CONCLUSION:
      Permanent HBP is a promising alternative for CRT. HBP may be considered as a
      rescue strategy for failed BVP and may be a reasonable primary alternative to BVP
      for CRT.

PMID- 29031930
TI  - Integrated structural and expression analysis implicate specific synaptic pathway
      in major depressive disorder.

PMID- 29031932
TI  - Appropriate use of opioid drugs: The importance of detecting vulnerable patients
      and health education.

PMID- 29031931
TI  - Global analysis of AGO2-bound RNAs reveals that miRNAs induce cleavage of target
      RNAs with limited complementarity.
AB  - Among the four Argonaute family members in mammals, only AGO2 protein retains
      endonuclease activity and facilitates cleavage of target RNAs base-pairing with
      highly complementary guide RNAs. Despite the deeply conserved catalytic activity,
      only a small number of targets have been reported to extensively base pair with
      cognate miRNAs to be cleaved by AGO2. Here, we analyzed AGO2-bound RNAs by
      CrossLinking ImmunoPrecipitation (CLIP) of genetically modified cells that
      express epitope-tagged AGO2 from the native genomic locus. We found that HMGA2
      mRNA is cleaved by AGO2 loaded with let-7 and miR-21. In contrast to the
      generally accepted notion, the base-pairing from the seed region to the cleavage
      site, rather than perfect or near perfect complementarity, was required for
      cleavage of the target mRNA in cells. Non-templated addition of nucleotides at
      the 3' end of the cleaved RNA was observed, further supporting the AGO2-mediated
      cleavage. Based on the observation that the limited complementarity is the
      minimum requirement for cleavage, we found that AGO2-mediated cleavage of targets
      is more common than previously thought. Our result may explain the vital role of
      endonuclease activity in controlling miRNA-mediated gene regulation.

PMID- 29031933
TI  - Relevant models and elements of integrated care for multi-morbidity: Results of a
      scoping review.
AB  - BACKGROUND: In order to provide adequate care for the growing group of persons
      with multi-morbidity, innovative integrated care programmes are appearing. The
      aims of the current scoping review were to i) identify relevant models and
      elements of integrated care for multi-morbidity and ii) to subsequently identify
      which of these models and elements are applied in integrated care programmes for
      multi-morbidity. METHODS: A scoping review was conducted in the following
      scientific databases: Cochrane, Embase, PubMed, PsycInfo, Scopus, Sociological
      Abstracts, Social Services Abstracts, and Web of Science. A search strategy
      encompassing a) models, elements and programmes, b) integrated care, and c) multi
      morbidity was used to identify both models and elements (aim 1) and implemented
      programmes of integrated care for multi-morbidity (aim 2). Data extraction was
      done by two independent reviewers. Besides general information on publications
      (e.g. publication year, geographical region, study design, and target group),
      data was extracted on models and elements that publications refer to, as well as
      which models and elements are applied in recently implemented programmes in the
      EU and US. RESULTS: In the review 11,641 articles were identified. After title
      and abstract screening, 272 articles remained. Full text screening resulted in
      the inclusion of 92 articles on models and elements, and 50 articles on
      programmes, of which 16 were unique programmes in the EU (n=11) and US (n=5).
      Wagner's Chronic Care Model (CCM) and the Guided Care Model (GCM) were most often
      referred to (CCM n=31; GCM n=6); the majority of the other models found were only
      referred to once (aim 1). Both the CCM and GCM focus on integrated care in
      general and do not explicitly focus on multi-morbidity. Identified elements of
      integrated care were clustered according to the WHO health system building
      blocks. Most elements pertained to 'service delivery'. Across all components, the
      five elements referred to most often are person-centred care, holistic or needs
      assessment, integration and coordination of care services and/or professionals,
      collaboration, and self-management (aim 1). Most (n=10) of the 16 identified
      implemented programmes for multi-morbidity referred to the CCM (aim 2). Of all
      identified programmes, the elements most often included were self-management,
      comprehensive assessment, interdisciplinary care or collaboration, person-centred
      care and electronic information system (aim 2). CONCLUSION: Most models and
      elements found in the literature focus on integrated care in general and do not
      explicitly focus on multi-morbidity. In line with this, most programmes
      identified in the literature build on the CCM. A comprehensive framework that
      better accounts for the complexities resulting from multi-morbidity is needed.

PMID- 29031934
TI  - "We don't have the infrastructure to support them at home": How health system
      inadequacies impact on long-term care admissions of people with dementia.
AB  - OBJECTIVES: The influence of healthcare system factors on long-term care
      admissions has received relatively little attention. We address this by examining
      how inadequacies in the healthcare system impact on long-term care admissions of
      people with dementia. This is done in the context of the Irish healthcare system.
      METHODS: Thirty-eight qualitative in-depth interviews with healthcare
      professionals and family carers were conducted. Interviews focused on
      participants' perceptions of the main factors which influence admission to long
      term care. Interviews were analysed thematically. RESULTS: The findings suggest
      that long-term care admissions of people with dementia may be affected by
      inadequacies in the healthcare system in three ways. Firstly, participants
      regarded the economic crisis in Ireland to have exacerbated the under-resourcing
      of community care services. These services were also reported to be inequitable.
      Consequently, the effectiveness of community care was seen to be limited.
      Secondly, such limits in community care appear to increase acute hospital
      admissions. Finally, admission of people with dementia to acute hospitals was
      believed to accelerate the journey towards long-term care. CONCLUSIONS:
      Inadequacies in the healthcare system are reported to have a substantial impact
      on the threshold for long-term care admissions. The findings indicate that we
      cannot fully understand the factors that predict long-term care admission of
      people with dementia without accounting for healthcare system factors on the
      continuation of homecare.

PMID- 29031935
TI  - Workplace mental health training for managers and its effect on sick leave in
      employees: a cluster randomised controlled trial.
AB  - BACKGROUND: Mental illness is one of the most rapidly increasing causes of long
      term sickness absence, despite improved rates of detection and development of
      more effective interventions. However, mental health training for managers might
      help improve occupational outcomes for people with mental health problems. We
      aimed to investigate the effect of mental health training on managers' knowledge,
      attitudes, confidence, and behaviour towards employees with mental health
      problems, and its effect on employee sickness absence. METHODS: We did a cluster
      randomised controlled trial of manager mental health training within a large
      Australian fire and rescue service, with a 6-month follow-up. Managers (clusters)
      at the level of duty commander or equivalent were randomly assigned (1:1) using
      an online random sequence generator to either a 4-h face-to-face RESPECT mental
      health training programme or a deferred training control group. Researchers,
      managers, and employees were not masked to the outcome of randomisation.
      Firefighters and station officers supervised by each manager were included in the
      study via their anonymised sickness absence records. The primary outcome measure
      was change in sickness absence among those supervised by each of the managers. We
      analysed rates of work-related sick leave and standard sick leave seperately,
      with rate being defined as sickness absence hours divided by the sum of hours of
      sickness absence and hours of attendance. This trial was registered with the
      Australian New Zealand Clinical Trials Registry (ACTRN12613001156774). FINDINGS:
      128 managers were recruited between Feb 18, 2014, and May 17, 2014. 46 (71%) of
      65 managers allocated to the intervention group received the intervention, and 42
      (67%) of 63 managers allocated to the control group were entered in the deferred
      training group. Managers and their employees were followed up and reassessed at 6
      months after randomisation. 25 managers (1233 employees) in the intervention
      group and 19 managers (733 employees) in the control group provided data for the
      primary analysis. During the 6-month follow-up, the mean rate of work-related
      sick leave decreased by 0.28 percentage points (pp) from a pre-training mean of
      1.56% (SE 0.23) in the intervention group and increased by 0.28 pp from 0.95%
      (0.20) in the control group (p=0.049), corresponding to a reduction of 6.45 h per
      employee per 6 months. The mean percentage of standard sick leave increased by
      0.48 pp from 4.97% (0.22) in the intervention group and by 0.31 pp from 5.27%
      (0.21) in the control group (p=0.169). INTERPRETATION: A 4-h manager mental
      health training programme could lead to a significant reduction in work-related
      sickness absence, with an associated return on investment of L9.98 for each pound
      spent on such training. Further research is needed to confirm these findings and
      test their applicability in other work settings. FUNDING: NSW Health and
      Employers Mutual Ltd.

PMID- 29031936
TI  - Workplace mental health programmes: the role of managers.

PMID- 29031937
TI  - Payer database and geospatial analysis to evaluate practice patterns in treating
      allergy in North Carolina.
AB  - OBJECTIVE: The objective of this study was to characterize the delivery of
      allergy care in North Carolina using a large payer charge database and
      visualization techniques. STUDY DESIGN: Geospatial database analysis. SETTING:
      North Carolina State claims database. SUBJECTS & METHODS: Medical data from the
      2013 FAIR Health National Private Insurance Claims (FH NPIC) database for North
      Carolina was mined for CPT codes and charges for allergy testing, and for the
      preparation and provision of allergen immunotherapy. Provider and patient
      variables were analyzed. Analyses were performed to compare differences in
      allergy care delivery. A visualization strategy complemented the analytic
      approach. RESULTS: 162,037 CPT charge entries were analyzed. Allergy-immunology
      specialists were the most common provider specialty to perform allergy
      immunotherapy treatments (68.9%, p<0.05). Among other specialties, there were no
      significant differences between specialists performing immunotherapy when
      comparing otolaryngology, family practice, and internal medicine (16.3%; 4.6%;
      2.6%; p>0.05). Providers with an M.D. degree were the most common provider type.
      The three most commonly treated diagnoses were allergic rhinitis variants.
      Females were more likely to receive allergy treatments versus males (55.9% vs.
      51.5%; p<0.001), and were more likely to receive allergy testing (65.3% vs.
      34.7%: p<0.005). Internal medicine providers charged higher than any other
      specialist type (p<0.05) for allergy immunotherapy. CONCLUSIONS: Using a large
      payer database coupled with visualization techniques was an efficient approach to
      characterizing the state-wide provision patterns of allergy diagnostic and
      therapy services in North Carolina. This first tier approach to efficiently
      exploring questions and describing populations is valuable.

PMID- 29031938
TI  - Design, synthesis and antiproliferative effect of 17beta-amide derivatives of 2
      methoxyestradiol and their studies on pharmacokinetics.
AB  - A series of 17beta-amide-2-methoxyestradiol compounds were synthesized with an
      aim to enhance the antiproliferative effect of 2-methoxyestradiol. The
      antiproliferative activity of 2-methoxyestradiol analogs against human cancer
      cells was investigated. 2-methoxy-3-benzyloxy-17beta-chloroacetamide-1,3,5(10)
      triene (5e) and 2-methoxy-3-hydroxy-17beta-butyramide-1,3,5(10)-triene (6c) had
      comparable or better antitumor activity than 2-methoxyestradiol. The elimination
      half-life of 6c (t1/2beta=240.93min) is ten times longer than 2-ME and the area
      under the curve was seven times (AUC0-tmin=2068.20+/-315.74MUgmL-1min) higher
      than 2-ME, respectively. Whereas 5e had similar pharmacokinetic behavior with 2
      ME (t1/2beta=22.28min) with a t1/2beta of 29.5 min. 6c had higher blood
      concentration, longer actuation duration and better suppression rate against S180
      mouse ascites tumor than 2-methoxyestradiol.

PMID- 29031939
TI  - Interest in Interventional Radiology at Different Stages of Training: Possible
      Implications for the New Integrated Interventional Radiology Residency.
AB  - PURPOSE: Integrated interventional radiology (IR) residencies recently underwent
      their second year in the match, the first year of which involved only a limited
      number of programs. Now that students can choose to enter IR directly, student
      perceptions of IR vs diagnostic radiology (DR) are of paramount importance.
      METHODS: We surveyed first- through fourth-year medical students and radiology
      residents regarding interest in IR vs DR. RESULTS: Students considering a
      radiological career expressed more interest in IR than DR. Conversely, residents
      expressed more interest in DR. CONCLUSIONS: Medical student advisors and IR
      programs should continue to anticipate a high number of applications for
      integrated IR positions.

PMID- 29031940
TI  - Ricin-like proteins from the castor plant do not influence liquid chromatography
      mass spectrometry detection of ricin in forensically relevant samples.
AB  - The toxic protein ricin (also known as RCA60), found in the seed of the castor
      plant (Ricinus communis) is frequently encountered in law enforcement
      investigations. The ability to detect ricin by analyzing its proteolytic
      (tryptic) peptides by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      is well established. However, ricin is just one member of a family of proteins in
      R. communis with closely related amino acid sequences, including R. communis
      agglutinin I (RCA120) and other ricin-like proteins (RLPs). Inferring the
      presence of ricin from its constituent peptides requires an understanding of the
      specificity, or uniqueness to ricin, of each peptide. Here we describe the set of
      ricin-derived tryptic peptides that can serve to uniquely identify ricin in
      distinction to closely-related RLPs and to proteins from other species. Other
      ricin-derived peptide sequences occur only in the castor plant, and still others
      are shared with unrelated species. We also characterized the occurrence and
      relative abundance of ricin and related proteins in an assortment of forensically
      relevant crude castor seed preparations. We find that whereas ricin and RCA120
      are abundant in castor seed extracts, other RLPs are not represented by abundant
      unique peptides. Therefore, the detection of peptides shared between ricin and
      RLPs (other than RCA120) in crude castor seed extracts most likely reflects the
      presence of ricin in the sample.

PMID- 29031941
TI  - The travel diaries of tetanus and botulinum neurotoxins.
AB  - Tetanus (TeNT) and botulinum (BoNT) neurotoxins, the causative agents of tetanus
      and botulism, respectively, are the most potent toxic molecules known to mankind.
      This extreme potency is attributed to: i) their specificity for essential
      components of the neurotransmitter release machinery present at vertebrate
      synapses, and ii) their high-affinity targeting to motor neurons by binding to
      polysialogangliosides and protein receptors. Comprising the clostridial
      neurotoxin family, TeNT and BoNTs engage distinct surface receptors and
      intracellular sorting pathways in neurons. BoNTs bind to the intraluminal domain
      of specific synaptic vesicle proteins that are exposed to the extracellular
      milieu upon exocytosis, and are taken up by synaptic vesicle recycling. A
      sizeable proportion of BoNT molecules remain at the neuromuscular junction, where
      their protease moiety is released into the cytoplasm, blocking synaptic
      transmission and causing flaccid paralysis. In contrast, TeNT undergoes binding
      to specific components of the basal membrane at the neuromuscular junction, is
      endocytosed into motor neurons and sorted to axonal signalling endosomes.
      Following this, TeNT is transported to the soma of motor neurons located in the
      spinal cord or brainstem, and then transcytosed to inhibitory interneurons, where
      it blocks synaptic transmission. TeNT-induced impairment of inhibitory input
      leads to hyperactivity of motor neurons, causing spastic paralysis, which is the
      hallmark of tetanus. This review examines the molecular mechanisms leading to the
      entry, sorting and intracellular trafficking of TeNT and BoNTs.

PMID- 29031942
TI  - Morbidity in New Zealand pesticide producers exposed to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD).
AB  - OBJECTIVES: To conduct a cross-sectional morbidity survey among 245 former
      employees of a pesticide production plant exposed to 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) in New Zealand. METHODS: Demographic factors and health information
      were collected in face-to-face interviews. TCDD, lipids, thyroid hormones,
      glucose and immunoglobulin G (IgG) were determined in non-fasting blood. For 111
      participants, a neurological examination was conducted. Associations between
      health outcomes and working in a TCDD exposed job (prevalence 49%) and serum TCDD
      concentration>=10pg/g lipid (18%) were assessed using logistic regression whilst
      controlling for age, gender, smoking, body mass index and ethnicity. RESULTS:
      Diabetes was more common in those who had worked in TCDD exposed jobs (OR 4.0,
      95%CI 1.0-15.4) and in those with serum TCDD >=10pg/g (OR 3.1, 95%CI 0.9-10.7).
      Non-fasting glucose levels >6.6mmol/l were more common in those with TCDD exposed
      jobs (OR 3.6, 95%CI 1.0-12.9), as were serum free thyroxine 4<12.8pmol/l (OR 4.5,
      95%CI 1.4-14.4), triglycerides >1.7mmol/l (OR 2.5, 95%CI 1.1-5.7) and high
      density lipoprotein cholesterol (HDL) <1mmol/l (OR 4.0, 95%CI 1.2-13.2). IgG was
      negatively associated with TCDD (linear regression p=0.05). The neurological
      examination revealed a higher frequency of abnormal reflexes in those with serum
      TCDD >=10pg/g (OR 4.8, 95%CI 1.1-21.0). CONCLUSIONS: In this occupationally
      exposed population, TCDD was associated with an increased risk of diabetes and a
      range of subclinical responses in multiple systems (peripheral nervous system,
      immune system, thyroid hormones and lipid metabolism), several decades after last
      exposure. These results need to be interpreted with caution due to the small
      study size and the cross-sectional nature of the study.

PMID- 29031943
TI  - Comment on: Systematic review and retrospective validation demonstrate prediction
      models can predict weight loss after bariatric surgery.

PMID- 29031944
TI  - Comparison of Lactic Acid Levels in Children with Suspected and Confirmed
      Intussusception.
AB  - BACKGROUND: Currently, no laboratory test can identify children with
      intussusception. Lactic acid is a marker of ischemia in gastrointestinal
      emergencies. OBJECTIVES: We present a case series comparing lactic acid levels in
      children with suspected and confirmed intussusception. METHODS: This is a
      prospective single case series of 39 patients who had suspected intussusception.
      Patients were eligible if they underwent abdominal ultrasound screening for
      suspected intussusception. Blood collected at the time of peripheral intravenous
      line placement was analyzed for lactic acid levels before ultrasound. RESULTS:
      Thirty-nine patients were enrolled; 16 were diagnosed with intussusception. Mean
      (+/- standard deviation) lactic acid levels were not significantly different
      between children with suspected (1.7 +/- 0.69 mmol/L) and confirmed
      intussusception (1.93 +/- 1.13 mmol/L). CONCLUSIONS: Lactic acid levels cannot
      identify children with intussusception.

PMID- 29031945
TI  - Assessing colour preference in Aldabra giant tortoises (Geochelone gigantea).
AB  - Tortoises perceive different colours and rely on the visual system to find food.
      However, few studies have considered colour preference in tortoises, especially
      in land species. The aim of this study is to investigate whether Aldabra giant
      tortoises (Geochelone gigantea) housed in Parco Natura Viva (VR), an Italian
      zoological garden, show a specific colour preference in their social context. The
      study was divided into two different periods in which red and yellow balls of the
      same size were scattered around in the outdoor enclosure. In the first period,
      pieces of carrots were placed behind each ball whereas in the second period,
      carrots were replaced with apples. Data on the frequencies of interaction with
      red and yellow balls were collected. First, tortoises interacted more with the
      balls when pieces of apples rather than carrots were hidden behind them. No
      significant group-level colour preference was found; however, individual-level
      variation in colour preference was reported. In addition, tortoises interacted
      significantly more with the yellow balls in the second than in the first period.
      Food typology seems therefore to play an important role in determining colour
      preference in chelonians. Research aimed at identifying individual differences in
      animal preferences might be valuable to improve captive animal husbandry (e.g.:
      development of enrichment programmes, diets and rewards).

PMID- 29031946
TI  - Spermatozoa DNA methylation patterns differ due to peripubertal age in bulls.
AB  - In the dairy industry, using semen as soon as the bull is mature enough to
      produce it is advantageous for breeding purposes. Mammalian spermatogenesis is a
      hormone-dependent developmental program in which a complex cascade of events must
      take place to ensure that germ cells reach the proper stage of development at the
      proper time. Conventional indicators of semen quality such as sperm cell motility
      and viability usually improve as bulls mature, meeting quality criteria
      satisfactorily at around 16 months. Using semen before that age may affect embryo
      viability, but other changes occurring during the peripubertal period should be
      considered. Although it is known that establishment of these patterns begins
      during foetal life, the extent to which sperm cell DNA methylation changes during
      puberty has not been studied. The aim of this study is to correlate the age of a
      young bull with the overall DNA methylation pattern of its spermatozoa.
      Spermatozoa were collected from bulls at the ages of 10 months (early pubertal),
      12 months (late pubertal) and 16 months (pubertal). Each animal (n = 4) was
      compared to itself with 16 months as control. Genome-wide DNA methylation was
      analyzed by microarray using the EmbryoGENE DNA Methylation Analysis platform.
      Using a fold change over 1.5 and a 5% FDR p-value correction, a total of 2602
      differently methylated regions were found in common between 10 months of age and
      16 months of age. No differently methylated regions between 12 months and 16
      months of age were found at the same level of statistical significance. We
      conclude that spermatozoa from bulls aged 10 months have a different epigenetic
      profile, which could compromise their value.

PMID- 29031947
TI  - The long-term survival of robotic lobectomy for non-small cell lung cancer: A
      multi-institutional study.
AB  - OBJECTIVE: Our objective is to report the world's largest series with the longest
      follow-up of robotic lobectomy for non-small cell lung cancer (NSCLC). METHODS:
      This was a multi-institutional retrospective review of a consecutive series of
      patients from 4 institutions' prospective robotic databases. RESULTS: There were
      1339 patients (men 55%, median age 68 years). The median operative time was 136
      minutes, median number of lymph nodes was 13 (5 N2 stations and 1 N1), median
      blood loss was 50 cc, and 4 (0.005%) patients received intraoperative
      transfusions. Conversions occurred in 116 patients (9%) and for bleeding in 24
      (2%). Median length of stay was 3 days. Major morbidity occurred in 8%. The 30
      day and 90-day operative mortality was 0.2% and 0.5%, respectively. Follow-up was
      complete in 99% of patients with a median follow-up of 30 months (range 1-154
      months). The 5-year stage-specific survival was: 83% for the 672 patients with
      stage IA NSCLC, 77% for the 281 patients with stage IB, 68% for the 118 patients
      with stage IIA, 70% for 99 patients with IIB, 62% for 143 patients with stage
      IIIA (122 had N2 disease, 73%), and 31% for 8 patients with stage IIIB (none had
      N3 disease). The cumulative incidence of metastatic NSCLC was 15% (128 patients,
      95% confidence interval, 13%-18%). The cumulative incidence of local recurrence
      in the ipsilateral operated chest was 3% only (26 patients, 95% confidence
      interval, 2%-5%). CONCLUSIONS: The oncologic results of robotic lobectomy for
      NSCLC are promising, especially for patients with pathologic N2 disease. However,
      further follow-up and studies are needed.

PMID- 29031948
TI  - Severe asthma: looking beyond the amount of medication.

PMID- 29031949
TI  - Evaluation of Irimedadi Taila as an adjunctive in treating plaque-induced
      gingivitis.
AB  - Ayurvedic drugs have been used since ancient times to treat diseases including
      periodontal diseases. Oral rinses made from ayurvedic medicines are used in
      periodontal therapy to control bleeding and reduce inflammation. To evaluate the
      efficacy of herbal preparation (Irimedadi taila) on reduction of plaque induced
      gingivitis. A total of 100 volunteers with clinical signs of mild to moderate
      gingivitis were selected and assigned to Group A (only scaling done) and Group B
      (scaling along with the use of Irimedadi taila). After recording the clinical
      parameters, the patients were instructed to use 2-3 drops of Irimedadi taila and
      gently massage the gums twice daily in Group B and oral hygiene instructions were
      given to all patients. Plaque and gingivitis assessment were carried out using
      the plaque index (Silness and Loe, 1964), Gingival index (Loe and Silness, 1963),
      and modified sulcular bleeding index (Mombelli et al.) at baseline and at 21 days
      post treatment. Statistically analysis was carried out using the student's paired
      t test for intra group comparison and unpaired t test for inter group comparison.
      Results showed that Irimedadi taila is effective in reducing gingival index and
      gingival bleeding index scores in comparison to scaling alone and the values are
      statistically significant with p < 0.0001. Irimedadi taila is effective in
      treatment of plaque induced gingivitis and can be effectively used as an adjunct
      to mechanical therapy.

PMID- 29031950
TI  - Identification of potential transcriptomic markers in developing asthma: An
      integrative analysis of gene expression profiles.
AB  - The goal of this study was to identify potential transcriptomic markers in
      developing asthma by an integrative analysis of multiple public microarray data
      sets. Using the R software and bioconductor packages, we performed a statistical
      analysis to identify differentially expressed (DE) genes in asthma, and further
      performed functional interpretation (enrichment analysis and co-expression
      network construction) and classification quality evaluation of the DE genes
      identified. 3 microarray datasets (192 cases and 91 controls in total) were
      collected for this analysis. 62 DE genes were identified in asthma, among which
      43 genes were up-regulated and 19 genes were down-regulated. The up-regulated
      gene with the highest Log2 Fold Change (LFC) was CLCA1 (LFC=2.81). The down
      regulated gene with the highest absolute LFC was BPIFA1 (LFC=-1.45). Enrichment
      analysis revealed that those DE genes strongly associated with proteolysis,
      retina homeostasis, humoral immune response, and salivary secretion. A support
      vector machine classifier (asthma versus healthy control) was also trained based
      on DE genes. In conclusion, the consistently DE genes identified in this study
      are suggested as candidate transcriptomic markers for asthma diagnosis, and
      provide novel insights into the pathogenesis of asthma.

PMID- 29031951
TI  - Potential of Cationic-Polymeric Nanoparticles for Oral Delivery of Naringenin: In
      Vitro and In Vivo Investigations.
AB  - The objective of the study was to improve the bioavailability and anticancer
      potential of naringenin (NRG) by developing a drug-loaded polymeric nanodelivery
      system. NRG-loaded eudragit E100 nanoparticle (NRG-EE100-NPs) system was
      developed and physicochemically characterized. In vivo pharmacokinetic and in
      vitro cytotoxicity abilities of the NRG-EE100-NPs were investigated. In vivo
      anticancer activity was evaluated in murine BALB/c mice-bearing colorectal tumor.
      The NRG-EE100-NPs had an optimum mean particle size (430.42 +/- 5.78 nm),
      polydispersity index (0.283 +/- 0.089) with percent entrapment efficiency (68.83
      +/- 3.45%). The NRG-EE100-NPs demonstrated significant higher bioavailability
      (~96-fold; p <0.05) as well as cytotoxicity (~16-fold; p <0.001) as compared to
      free NRG. Furthermore, NRG-EE100-NPs indicated significant tumor suppression (p
      <0.01) subsequently improvement in survival rate compared to free NRG in vivo.
      Thus, the physicochemical properties and colorectal cancer efficacy of NRG were
      improved by successful encapsulating in cationic-polymeric nanoparticle system.

PMID- 29031953
TI  - Stable and Fast-Dissolving Amorphous Drug Composites Preparation via Impregnation
      of Neusilin(r) UFL2.
AB  - A promising approach to increase the aqueous solubility, hence the
      bioavailability, of poorly water-soluble drugs is to convert them into their
      amorphous state through impregnation into mesoporous silica. Unfortunately,
      mesoporous silica is not yet available in bulk quantities due to high
      manufacturing costs. In this work, feasibility of using a commercially available
      cost-effective mesoporous fine grade Neusilin(r) UFL2 to prepare amorphous drug
      composites of 2 model poorly soluble drugs, fenofibrate and itraconazole, is
      established. In contrast to fluidized-bed spray-impregnation, only mixing and
      drying steps are required. Complimentary assessment using X-ray powder
      diffraction, differential scanning calorimetry, and Raman spectroscopy confirmed
      drug within the composites to be amorphous at as high as 30% drug loading both
      after formation and after 3 months of storage at 40 degrees C and 75% relative
      humidity. Amorphous drug recrystallization was completely suppressed due to the
      confinement effect due to the Neusilin(r). The amorphous drug composites resulted
      in higher apparent solubility and faster dissolution rate of the model drugs as
      compared to their crystalline counterpart, confirmed by United States
      Pharmacopeia II dissolution and ultraviolet surface dissolution imaging. Overall,
      stable, high drug-loaded fast-dissolving amorphous drug composites preparation
      using Neusilin(r) UFL2 is demonstrated as a promising approach to enhance
      solubility of poorly soluble drugs.

PMID- 29031952
TI  - Antitumor Efficacy and Toxicity of 5-Fluorouracil-Loaded Poly(Lactide Co
      glycolide) Pellets.
AB  - The aim of this study was to formulate a biodegradable implant capable of
      imparting local antitumor activity through the sustained release of the
      chemotherapeutic agent, 5-fluorouracil (5-FU). Thus, injectable pellets (<1.2 mm
      diameter) made from poly(lactide co-glycolide) (PLGA) and loaded with 5-FU at
      varying drug:polymer ratios were fabricated using hot-melt extrusion and tested
      for their ability to provide sustained release of 5-FU in in vitro and in vivo
      settings. In addition, these formulations were compared against soluble 5-FU for
      their antitumor activity in vivo as well as for their toxicity. It was
      demonstrated that the release rate of 5-FU from PLGA pellets was directly related
      to the percentage of 5-FU in the pellets. PLGA pellets loaded with 50% w/w 5-FU
      exhibited comparable, and significantly enhanced, antitumor activity (as measured
      by tumor volumes and survival) in vivo in a thymoma and colon cancer model,
      respectively, when compared to an equivalent bolus dose (120 mg/kg) of soluble 5
      FU. We concluded that 5-FU-loaded PLGA pellets were more effective and
      specifically less erythrotoxic than 5-FU bolus injections and therefore may prove
      to be of benefit as an intraoperative adjunct therapy for patients with cancers
      that are sensitive to 5-FU and who are undergoing tumor resection.

PMID- 29031954
TI  - Suitability of the AUC Ratio as an Indicator of the Pharmacokinetic Advantage in
      HIPEC.
AB  - The purpose of this study was to evaluate the area under the concentration-time
      curve (AUC) ratio as an optimal indicator of the pharmacokinetic advantage during
      hyperthermic intraperitoneal perioperative chemotherapy. The impact on the AUC
      ratio on the variables related to the calculation of systemic drug exposure,
      instillation time, and peripheral drug distribution was evaluated through
      simulations as well as through a retrospective analysis of studies published in
      the literature. Both model simulations and the retrospective analysis showed that
      the 3 variables evaluated had an impact on the AUC ratio value if the complete
      systemic exposure was not fully considered. However, when that complete systemic
      exposure was considered, none of these variables affected the AUC ratio value.
      AUC ratio is not a characteristic parameter of a drug if the calculated systemic
      drug exposure is not complete. Thus, AUC ratio is not valid for comparing the
      pharmacokinetic advantage of 2 drugs, and it should not be employed to prove
      whether a drug can be used in hyperthermic intraperitoneal perioperative
      chemotherapy safely with regard to toxicity. As an alternative, the study of the
      absorption rate constant and the bioavailability are proposed as the true and
      independent parameters that reflect the amount of drug absorbed.

PMID- 29031955
TI  - Determination of Nonspherical Morphology of Doxorubicin-Loaded Liposomes by
      Atomic Force Microscopy.
AB  - The 3-D morphology of doxorubicin (DOX)-loaded liposomes with a size of circa 100
      nm was characterized by atomic force microscopy in an aqueous environment.
      Prolate liposomes appear in accordance with linear expansion of DOX fiber bundles
      precipitated inside liposomes. Oblate and concave liposomes were simultaneously
      observed with increased DOX concentrations; however, their morphologies were not
      readily determined by 2-D cryo-TEM imaging. Precise data analysis of the 3-D
      parameters of each liposome allowed semiquantitative evaluation of the
      transformation of spherical liposomes into nonspherical-prolate, oblate, and
      concave liposomes. In addition, nonspherical liposomes became spherical on the
      replacement of the liposomal outer phase consisting of a sucrose solution, with
      water and subsequent water influx. All spherical liposomes transformed into
      oblate and concave liposomes with a return to hyperosmotic conditions, when
      transferred from water to sucrose solution. Furthermore, the concave liposomes
      did not appear under DOX incubation conditions (65 degrees C), which could be due
      to the amorphous and supersaturated DOX inside the liposomes that restrained
      liposomal shrinkage. As atomic force microscopy has improved our ability to image
      3-D morphologies of liposomes in various conditions, it is an alternative
      analytical tool to cryo-TEM and may have future applications in regulatory tests
      for quality control and assurance.

PMID- 29031956
TI  - The Solubility-Permeability Trade-Off of Progesterone With Cyclodextrins Under
      Physiological Conditions: Experimental Observations and Computer Simulations.
AB  - This study intended to evaluate the effect of cyclodextrins on the apparent
      solubility and permeability of lipophilic drugs under physiological conditions
      and establish in silico model to choose the optimal amount of cyclodextrins for
      cyclodextrin-containing oral formulations. In order to study the effect of
      cyclodextrins under physiological conditions, bile salts and lecithin were added
      into the rat intestinal perfusion solution to simulate the fasted intestinal
      fluid. In addition, the in vivo oral absorption performances of cyclodextrin
      containing formulations were simulated by gastrointestinal simulation technology
      based on the advanced compartmental absorption and transit model. The
      permeability of progesterone was not significantly different between 0.1 mM and 1
      mM of 2-hydroxypropyl-beta-cyclodextrins (HP-beta-CD) under physiological
      conditions. When the concentration of HP-beta-CD was 1 mM, the permeability of
      progesterone under physiological conditions was significantly higher than that in
      vitro. The in silico model established in this study was validated by in vivo
      studies of 4 formulations containing different dosage of cyclodextrin, proving
      that it was accurate and reliable. In conclusion, this work that demonstrates the
      permeability of lipophilic drugs could not decrease quickly among a certain range
      of dosage of HP-beta-CD in vivo. Studying the solubility-permeability interplay
      under physiological conditions would be more meaningful.

PMID- 29031957
TI  - Exercise training attenuates experimental autoimmune encephalomyelitis by
      peripheral immunomodulation rather than direct neuroprotection.
AB  - BACKGROUND: Conflicting results exist on the effects of exercise training (ET) on
      Experimental Autoimmune Encephalomyelitis (EAE), nor is it known how exercise
      impacts on disease progression. OBJECTIVE: We examined whether ET ameliorates the
      development of EAE by modulating the systemic immune system or exerting direct
      neuroprotective effects on the CNS. METHODS: Healthy mice were subjected to
      6weeks of motorized treadmill running. The Proteolipid protein (PLP)-induced
      transfer EAE model in mice was utilized. To assess effects of ET on systemic
      autoimmunity, lymph-node (LN)-T cells from trained- vs. sedentary donor mice were
      transferred to naive recipients. To assess direct neuroprotective effects of ET,
      PLP-reactive LN-T cells were transferred into recipient mice that were trained
      prior to EAE transfer or to sedentary mice. EAE severity was assessed in vivo and
      the characteristics of encephalitogenic LN-T cells derived from PLP-immunized
      mice were evaluated in vitro. RESULTS: LN-T cells obtained from trained mice
      induced an attenuated clinical and pathological EAE in recipient mice vs. cells
      derived from sedentary animals. Training inhibited the activation, proliferation
      and cytokine gene expression of PLP-reactive T cells in response to CNS-derived
      autoantigen, but strongly enhanced their proliferation in response to
      Concanavalin A, a non-specific stimulus. However, there was no difference in EAE
      severity when autoreactive encephalitogenic T cells were transferred to trained
      vs. sedentary recipient mice. CONCLUSION: ET inhibits immune system responses to
      an auto-antigen to attenuate EAE, rather than generally suppressing the immune
      system, but does not induce a direct neuro-protective effect against EAE.

PMID- 29031959
TI  - Well-dispersed palladium nanoparticles on nickel- phosphorus nanosheets as
      efficient three-dimensional platform for superior catalytic glucose electro
      oxidation and non-enzymatic sensing.
AB  - In this work, we report a novel well-dispersed palladium nanoparticles
      (PdNPs)/nickel-phosphorus nanosheets (Ni-P NSs) synthesized by combination of red
      phosphorous phosphorization and simple electrodeposition technique. The obtained
      PdNPs/Ni-P nanosheets framework with large electrochemical active surface would
      not only exhibit much superior electrocatalytic activity (180.5+/-3.07mAcm-2)
      toward glucose oxidation reaction, but also represent a wide linear range (2MUM
      4.65mM) and high sensitive detection of glucose (242.5+/-3.28MUAmM-1cm-2) as non
      enzymatic glucose sensor. The three- dimensional (3D) PdNPs/Ni-P nanosheets have
      a promising prospect as a novel kind of highly active nanocatalyst and non
      enzymatic electrochemical sensor.

PMID- 29031958
TI  - Reference values and reliability for lumbopelvic strength and endurance in
      asymptomatic subjects.
AB  - BACKGROUND: Assessing the lumbopelvic region is useful for detecting many
      musculoskeletal dysfunctions and also performance deficits. Several clinical
      tests are used to assess this region, however, reference values and results
      related to method, reliability and error measurements of these tests have not
      been reported. OBJECTIVES: To establish reference values and determine
      reliability, standard error of measurement (SEM), typical error of measurement
      (TEM) and minimum detectable change (MDC) of a set of clinical tests used for
      assessing the lumbopelvic region in subjects divided by gender, age group and
      physical activity levels. METHODS: An observational study was conducted. For
      reference values, 152 subjects performed eight clinical tests (isometric strength
      of hip muscles; deep abdominal function and endurance tests) used to assess the
      lumbopelvic region. Reliability analyses were assessed using the Intraclass
      Correlation Coefficient (ICC2,1) and error measurements were calculated by using
      the SEM, TEM and the MDC. RESULTS: Reference values were established for each
      group and results showed significant (p<0.05) differences concerning gender, age
      group and physical activity levels in clinical tests. All tests presented good
      reliability indices with an ICC higher than 0.80 for reliability; MDC values were
      greater than mean of SEM in all tests, confirming its usage for clinical practice
      assessments. CONCLUSION: Reference values are necessary in the evaluation of
      subjects and these results can contribute for clinical practice, providing
      clinical training targets. Also, evaluation of reliability and error measurements
      in this set of tests allows its use in clinical practice.

PMID- 29031960
TI  - The effect of post-synthesis aging on the ligand exchange activity of iron oxide
      nanoparticles.
AB  - HYPOTHESIS: Ligand exchange is a widely-used method of controlling the surface
      chemistry of nanomaterials. Exchange is dependent on many factors including the
      age of the core particle being modified. Aging of the particles can impact
      surface structure and composition, which in turn can affect ligand binding.
      EXPERIMENTS: To quantify the effects of aging on ligand exchange, we employed a
      technique to track the exchange of radiolabeled 14C-oleic acid with unlabeled,
      oleic acid bound to iron oxide nanoparticles. Liquid scintillation counting (LSC)
      was used to determine the amount of 14C-oleic acid adsorbing to the particles
      throughout the duration of the exchange for particles aged for 2days, 7days, and
      30days. FINDINGS: Results revealed an increase in the total amount of ligands
      exchanged with aging up to 30days. Kinetic analysis of these results revealed a
      significant decrease in the overall rate of ligand exchange between 2 and 30days.
      The change in extent of adsorption with age could suggest increased availability
      of free binding sites. A follow-up study comparing exchange with oxidized and
      unoxidized particles suggested this increase in ligand adsorption may be due to
      changes in the Fe2+/Fe3+ ratio on the surface as the particles aged.

PMID- 29031961
TI  - Fabrication of cobalt ferrite/cobalt sulfide hybrid nanotubes with enhanced
      peroxidase-like activity for colorimetric detection of dopamine.
AB  - The development of highly sensitive and low-cost biosensors for the detection of
      dopamine is of paramount importance for medical diagnostics. Herein, we report
      the preparation of a new peroxidase-like catalyst with a uniform heterostructure
      by using a technique involving electrospinning, annealing and solvothermal
      reaction. In this catalyst system, cobalt sulfide (CoS) nanoparticles were
      homogenously distributed and supported on the surface of cobalt ferrite (CoFe2O4)
      nanotubes. The as-prepared CoFe2O4/CoS hybrid nanotubes showed remarkably high
      catalytic efficiency as peroxidase mimics toward the oxidation of 3,3,5,5
      tetramethylbenzidine (TMB) in the presence of H2O2. Owing to the synergistic
      effect between the CoFe2O4 and CoS component, the prepared CoFe2O4/CoS hybrid
      nanotubes exhibited enhanced peroxidase-like activity, exceeding that of either
      the CoS nanoparticles or CoFe2O4 nanotubes alone. Dopamine has been widely
      investigated due to its unique function in the nervous system. Consequently,
      various approaches have been developed for the sensitive determination of
      dopamine. In this work, a simple and sensitive colorimetric route for the
      detection of dopamine was established based on the ability of dopamine to induce
      the reduction of oxidized TMB to TMB with consequent fading of the blue color.
      This method shows a wide linear range (0-50MUM) and a low detection limit of
      0.58MUM. The unique heterostructure with spinel/sulfide interfaces represents a
      new concept for the construction of highly efficient and multifunctional
      biocatalysts.

PMID- 29031962
TI  - [Asthma control and quality of life].
AB  - INTRODUCTION: The assessment of asthma control is based on objective measures:
      clinical, pharmacological and spirometry. However subjective component may be
      also necessary for assessing asthma control. OBJECTIVES: To study the feasibility
      and clinical value of the assessment of the quality of life of patients with
      asthma by the SF-36 (Medical Outcomes Study Short Form) and the possible
      existence of a correlation between controlled asthma and a better quality of
      life. PATIENTS AND METHODS: A prospective study that included 167 patients with
      asthma in a stable condition. Control of asthma and SF-36 were established three
      months after the inclusion of patients. RESULTS: The SF-36 was lower in the
      uncontrolled group in all areas of the physical component and the difference was
      significant in the "limitation related to physical activity" and "perceived
      health". In the mental component, the score was lower in "mental health" and the
      "limitation due to mental state" in the group with uncontrolled asthma and the
      difference was significant only in the limitation due to mental state (P=0.043).
      CONCLUSION: The quality of life of asthmatic patients is correlated to the
      control of this disease.

PMID- 29031963
TI  - [Spirometric and radiographic profile of patients with pulmonary tuberculosis
      treated and cured at the Department of Pulmonology of Brazzaville University
      Hospital].
AB  - INTRODUCTION: Tuberculosis is a real public health problem in Congo. Pulmonary
      localization can lead to sequelae of respiratory functional repercussions.
      OBJECTIVE: Describe the spirometric and radiographic profile of patients treated
      with pulmonary tuberculosis treated and cured. PATIENTS AND METHODS: This was a
      cross-sectional study that included 150 patients with previous pulmonary
      tuberculosis with positive microscopy treated and cured in the Pulmonary
      Department of Brazzaville University Hospital. In which we performed a functional
      exploration (Spirometry) and a chest X-ray. The study took place from 1st January
      2016 to 31st August 2016. RESULTS: The spirometry performed in all patients was
      pathological in 68.67% (103 cases/150) of the cases. Among them 74.76% (77
      cases/103) had a restrictive profile (FEV1/FVC >70% and CVF <80%), 9.71% (10
      cases/103) an obstructive syndrome (FEV1/FVC <=70% and CVF >80%) and 15.53% (16
      cases/103) a mixed syndrome (FVC <80% and FEV1/FVC <70%). Of the 150 chest
      radiographs performed, 120 or 80% were pathological; the degree of parenchymal
      stage III destruction represented 28.33%. There was a significant correlation
      between the degree of parenchymal destruction and the delay in treatment on the
      one hand and between the degree of parenchymal destruction and the different
      pulmonary volumes and volumes on the other hand. CONCLUSION: The prevention of
      these respiratory functional disorders is based on the prophylaxis of
      tuberculosis on early diagnosis of the disease.

PMID- 29031964
TI  - [The thoracic surgeon and the management of the bronchial biliary fistula of
      hydatid origin].
AB  - INTRODUCTION: The bronchial biliary fistula surgery is a major one, always going
      with a higher rate of complication especially in case of bile duct obstruction.
      The aim of this study is to find out the contribution of endoscopic
      sphincterotomy while reporting the results of surgical treatment of bronchial
      biliary fistulae by exclusive thoracotomy. METHODS: This was a retrospective
      study, which took place in the Department of Thoracic Surgery, University
      Hospital Hassan II, from January 2009 to March 2016. The parameters studied in
      connection with the bronchial biliary fistula of hydatid origin were: age, sex,
      origin, history of surgery especially for hepatic hydatid cyst, term of
      bilyptysie, imaging results, preoperative cholangiography indications, surgical
      treatment modalities and patients trends. RESULTS: A sample of 12 patients was
      included (6 men and 6 women) with an average age of 44 years old, with a gap
      spanning between 17 and 81 years. Seven patients had at least a history of
      hepatic hydatid surgery. The biliptysie was the main symptom in 8 patients. A
      biological cholestasis syndrome was found in 6 patients. The thoracoabdominal CT
      scan performed on all patients comes out with results in 100% of cases. Four
      patients received endoscopic retrograde cholangiography that allowed them to
      release the bile duct completely by sphincterotomy with extraction of hydatid
      membrane in one patient and with development of a biliary stent in another
      patient. The incision was a low posterolateral thoracotomy in 10 patients that
      went under surgery. It has allowed to deal in one-time liver and lung injuries
      combined with diaphragmatic breach repair. Inside the group of patients that went
      under surgery, the postoperative results were simple in 8 cases. We have noted an
      overall mortality rate of 18.2%. CONCLUSION: Bronchial biliary fistula surgery
      complications remains considerable despite the progress of diagnostic imaging.
      Preoperative endoscopic sphincterotomy is a milestone in the handling of this
      surgery. It may even be suggested as exclusive therapy in inoperable patients
      with significant biliptisy.

PMID- 29031965
TI  - [Bronchial carcinoid tumor and recurrent pneumothoraxes].
AB  - Pneumothorax is a rare clinical manifestation of lung cancer. It can
      exceptionally reveal a bronchial carcinoid tumor. We present the case of a 27
      year-old woman in whom recurrent pneumothoraxes were the clinical manifestation
      of a bronchial carcinoid tumor. The interest for chest computed tomography and
      bronchoscopy to identify etiology of secondary pneumothoraxes will be discussed.

PMID- 29031966
TI  - BINK: Biological binary keypoint descriptor.
AB  - Learning robust keypoint descriptors has become an active research area in the
      past decade. Matching local features is not only important for computational
      applications, but may also play an important role in early biological vision for
      disparity and motion processing. Although there were already some floating-point
      descriptors like SIFT and SURF that can yield high matching rates, the need for
      better and faster descriptors for real-time applications and embedded devices
      with low computational power led to the development of binary descriptors, which
      are usually much faster to compute and to match. Most of these descriptors are
      based on purely computational methods. The few descriptors that take some
      inspiration from biological systems are still lagging behind in terms of
      performance. In this paper, we propose a new biologically inspired binary
      keypoint descriptor: BINK. Built on responses of cortical V1 cells, it
      significantly outperforms the other biologically inspired descriptors. The new
      descriptor can be easily integrated with a V1-based keypoint detector that we
      previously developed for real-time applications.

PMID- 29031967
TI  - Profiling of a wide range of neurochemicals in human urine by very-high
      performance liquid chromatography-tandem mass spectrometry combined with in situ
      selective derivatization.
AB  - Development of a reliable analytical method of neurochemicals in biological
      fluids is important to discover potential biomarkers for the diagnosis, treatment
      and prognosis of neurological disorders. However, neurochemical profiling of
      biological samples is challenging because of highly different polarities between
      basic and acidic neurochemicals, low physiological levels, and high matrix
      interference in biological samples. In this study, an ultra-performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS) method combined with in situ
      selective derivatization for comprehensive profiling of 20 neurochemicals in
      urine was developed for a wide range of neurochemicals. In situ selective
      derivatization greatly improved the peak capacity on a reversed-phase C18 column
      and sensitive mass detection in LC-ESI-MS/MS-positive ion mode due to reduction
      of the distinct physicochemical properties between acidic and basic
      neurochemicals. The MS/MS spectra of neurochemicals exhibited specific ions, such
      as losses of amine, methanol, or methyl formate molecules from protonated
      molecules, enabling selection of appropriate multiple reaction monitoring (MRM)
      ions for selective and sensitive detection. The developed method was validated in
      terms of linearity, limit of detection (LOD) and limit of quantification (LOQ),
      precision, accuracy, and recovery. The correlation coefficients (R2) of
      calibration curves were above 0.9961. The ranges of LODs and LOQs were 0.1
      3.6ng/mL and 0.3-12.0ng/mL, respectively. The overall precision and accuracy were
      0.52-16.74% and 82.26-118.17%, respectively. The method was successfully applied
      to simultaneously profile the metabolic pathways of tyrosine, tryptophan, and
      glutamate in Parkinson's disease patient urine (PD, n=21) and control urine
      (n=10). Significant differences (P<=0.01) between two groups in the activity of
      phenylethanolamine N-methyltransferase (PNMT) and alcohol dehydrogenase (ADH)
      were observed. In conclusion, this method provides reliable quantification of a
      wide range of neurochemicals in human urine and would be helpful for finding
      biomarkers related to specific neuronal diseases.

PMID- 29031968
TI  - Pyrolysis-gas chromatography-isotope ratio mass spectrometry for monitoring
      natural additives in polylactic acid active food packages.
AB  - Compound-specific isotope analysis (CSIA) usually requires preparative steps
      (pretreatments, extraction, derivatization) to get amenable chromatographic
      analytes from bulk geological, biological or synthetic materials. Analytical
      pyrolysis (Py-GC/MS) can help to overcome such sample manipulation. This
      communication describe the results obtained by hyphenating analytical pyrolysis
      (Py-GC) with carbon isotope-ratio mass spectrometry (IRMS) for the analysis of a
      polylactic acid (PLA) a based bio-plastic extruded with variable quantities of a
      natural plant extract or oregano essential oil. The chemical structural
      information of pyrolysates was first determined by conventional analytical
      pyrolysis and the measure of delta13C in specific compounds was done by coupling
      a pyrolysis unit to a gas chromatograph connected to a continuous flow IRMS unit
      (Py-GC-C-IRMS). Using this Py-CSIA device it was possible to trace natural
      additives with depleted delta13C values produced by C3 photosystem vegetation
      (cymene: -26.70/00+/-2.52; terpinene: -27.10/00+/-0.13 and carvacrol: -27.50/00+/
      1.80 from oregano and two unknown structures: -23.30/00+/-3.32 and -24.40/00+/
      1.70 and butyl valerate: -24.10/00+/-3.55 from Allium spp.), within the naturally
      isotopically enriched bio-plastic backbone derived from corn (C4 vegetation)
      starch (cyclopentanones: -14.20/00+/-2.11; lactide enantiomers: -9.20/00+/-1.56
      and larger polymeric units: -17.20/00+/-1.71). This is the first application of
      Py-CSIA to characterize a bio-plastic and is shown as a promising tool to study
      such materials, providing not only a fingerprinting, but also valuable
      information about the origin of the materials, allowing the traceability of
      additives and minimizing sample preparation.

PMID- 29031969
TI  - Influence of natural organic matter on the extraction efficiency of flame
      retardants from surface waters.
AB  - The influence of natural organic matter (NOM) on the solid-phase extraction (SPE)
      efficiency was investigated for legacy and emerging flame retardants (FRs; n=26)
      in surface water. Three different groups of FRs were analyzed: polybrominated
      diphenyl ethers (PBDEs), halogenated flame retardants (HFRs), and
      organophosphorus flame retardants (OPFRs). In addition, five sorbents (Amberlite
      XAD-2, Amberlite IRA-743, Oasis HLB, Chromabond HR-P, and Chromabond HR-X) were
      evaluated for the extraction of FRs (n=33) in water, of which Oasis HLB eluted
      with dichloromethane and acetone:n-hexane (1:1, v/v) provided the highest overall
      recoveries. In subsequent NOM experiments, where FRs were extracted from water
      containing different NOM concentrations, both increased and decreased extraction
      efficiency with increasing NOM level were observed. Physicochemical and semi
      empirical quantum chemistry properties were calculated for the FRs and used for
      analyzing relations between FRs. Principal component analysis (PCA) and
      hierarchical cluster analysis (HCA) showed that the FRs separated into four
      different groups based on their properties. The FRs within each group responded
      similarly to increasing NOM, while differences in behavior were observed between
      the groups. This suggests that the structural properties of micropollutants
      highly influence NOM-FR interaction mechanisms. For instance, at high NOM levels,
      recoveries decreased substantially for FRs containing a moiety that can form
      strong hydrogen bonds (such as the double-bonded oxygen in e.g., OPFRs). Many of
      the compounds showed maximum extraction efficiency at higher levels of NOM. This
      suggests that binding of NOM to the sorbent and subsequent interaction between
      sorbent-bound NOM and FRs is an important mechanism for extraction of
      micropollutants from surface waters.

PMID- 29031970
TI  - Adsorption equilibrium and kinetics of Immunoglobulin G on a mixed-mode adsorbent
      in batch and packed bed configuration.
AB  - It is commonly accepted that efficient protein separation and purification to the
      desired level of purity is one bottleneck in pharmaceutical industries. MabDirect
      MM is a new type of mixed mode adsorbent, especially designed to operate in
      expanded bed adsorption (EBA) mode. In this study, equilibrium and kinetics
      experiments were carried out for the adsorption of Human Immunoglobulin G (hIgG)
      protein on this new adsorbent. The effects of ionic strength and pH are assessed.
      Langmuir isotherms parameters are obtained along with the estimation of the
      effective pore diffusion coefficient (Dpe) by fitting the batch adsorption
      kinetics experiments with the pore diffusion model. The maximum adsorption of the
      IgG protein on the MabDirect MM adsorbent, 149.7+/-7.1mg.gdry-1, was observed
      from a pH 5.0 buffer solution without salt addition. Adding salt to the buffer
      solution, and/or increasing pH, decreases the adsorption capacity which is 4.7+/
      0.4mg.gdry-1 for pH 7.0 with 0.4M NaCl in solution. Regarding the Dpe estimation,
      a value of 15.4*10-6cm2.min-1 was obtained for a pH 5.0 solution without salt.
      Increasing the salt concentration and/or the pH value will decrease the effective
      pore diffusion, the lowest Dpe (0.16*10-6cm2.min-1) value being observed for an
      IgG solution at pH 7.0 with 0.4M NaCl. Fixed bed experiments were conducted with
      the purpose to validate the equilibrium and kinetic parameters obtained in batch.
      For a feed concentration of 0.5 g.L-1 of IgG in pH 5.0 buffer solution with 0.4M
      NaCl, a dynamic binding capacity at 10% of breakthrough of 5.3mg.gwet-1
      (15.4mgIgG.mLresin-1) was obtained, representing 62% of the saturation capacity.
      As far as the authors know, this study is the first one concerning the adsorption
      of hIgG on this type of mixed mode chromatography adsorbent.

PMID- 29031971
TI  - Solid-phase extraction followed by liquid chromatography-high resolution mass
      spectrometry to determine synthetic cathinones in different types of
      environmental water samples.
AB  - Synthetic cathinones have become popular in recent years, which would explain why
      their determination in influent sewage samples has already been documented. In
      the present study a method based on solid-phase extraction followed by liquid
      chromatography and high resolution mass spectrometry is developed, validated and
      applied to determine twelve cathinones and one of their metabolites in different
      environmental samples including influent and effluent sewage and river water. Two
      cation-exchange sorbents (Oasis MCX and Oasis WCX) were compared, with better
      results achieved with Oasis WCX in terms of apparent recoveries (70-100%) and
      matrix effects (lower than -34%). The method was validated with effluent sewage
      samples providing suitable figures of merit, with method quantification limits
      ranging from 1ng/L to 5ng/L and method detection limits from 0.1ng/L to 0.5ng/L
      for all the compounds. Of the different cathinones studied, three, namely
      methylone, mephedrone metabolite and methylenedioxypyrovalerone, were quantified
      at concentration levels of low ng/L in each of the different samples analysed,
      while a number of the other cathinones were also detected in some of the samples.

PMID- 29031972
TI  - Selective two-dimensional effect-directed analysis with thin-layer
      chromatography.
AB  - There are thousands of organic trace substances in the environment that are not
      fully characterized, and evaluation of their relevance to the ecosystem is
      difficult. Effect-directed analysis (EDA) is a suitable tool to assess the
      effects of a substance via in-vitro bioassays, which can provide information
      about the relevance of the substance. High-performance thin-layer chromatography
      (HPTLC) has been shown to be a good method for fractionation. Environmental
      samples, however, often have high complexity, which is why the peak capacity of
      HPTLC is not sufficient. Therefore, this study focused on the development of
      selective two-dimensional (2D) HPTLC-EDA to increase the peak capacity and
      facilitate the identification of effective compounds. Thus, only effective zones
      were selected in the first dimension in terms of heart-cutting and were
      transferred to the second dimension through elution head-based extraction. Three
      2D approaches were developed and validated. The best results in terms of peak
      capacity and orthogonality were achieved when the retardation factors of the
      first dimension were used to adjust the mobile phase (MP) for the second
      dimension. Applying the acetylcholinesterase (AChE) inhibition assay as an
      example EDA, analysis of spiked surface water by 2D HPTLC-EDA allowed zones with
      neurotoxic effects to responsible substances to be assigned. The 2D separation
      reduced the complexity of effective zones and thus facilitated the subsequent
      identification of effective compounds. Knowledge about a substances effects
      enabled assessment of its relevance to the environment.

PMID- 29031973
TI  - Predicting Solubility/Miscibility in Amorphous Dispersions: It Is Time to Move
      Beyond Regular Solution Theories.
AB  - The evolving challenges associated with the development of poorly soluble drug
      molecules have been met with major advances in drug solubilization. In
      particular, amorphous solid dispersion technology is becoming an increasingly
      important option to enhance oral bioavailability by creating prolonged drug
      supersaturation to maximize the driving force for intestinal absorption. A
      primary concern in the development of amorphous solid dispersions is their
      physical stability, leading to increasing interest in predictive methodologies to
      assess the propensity for drug crystallization under various storage conditions.
      For most drug-excipient combinations of pharmaceutical interest, hydrogen bonding
      is an important factor in determining miscibility, supersaturation potential, and
      the influence of water uptake during storage and after administration. The vast
      majority of publications to date have utilized mathematical models based on
      regular solution theory such as Flory-Huggins theory to predict drug-polymer
      miscibility, despite the fact that they were never intended to be applied to
      hydrogen-bonded systems. In this commentary article, regular solution theory is
      applied to simple hydrogen-bonded alcohol-alkane solutions to explore trends in
      the Flory-Huggins chi interaction parameter and possible pitfalls in its
      interpretation. More recent models that explicitly allow for specific
      interactions merit greater attention.

PMID- 29031974
TI  - In Situ Monitoring and Modeling of the Solution-Mediated Polymorphic
      Transformation of Rifampicin: From Form II to Form I.
AB  - In this article, the solution-mediated polymorphic transformation of rifampicin
      was investigated and simulated in 3 solvents at 30 degrees C. The solid-state
      form I and form II of rifampicin was characterized by powder X-ray diffraction,
      scanning electron microscopy, thermogravimetric analysis, Raman spectroscopy, and
      Fourier transform infrared spectroscopy (FTIR). To explore the relative
      stability, solubility data of form I and form II of rifampicin in butan-1-ol were
      determined using a dynamical method. In addition, Raman spectroscopy and focused
      beam reflectance measurement were used to in situ monitor the transformation of
      rifampicin from form II to form I. The liquid state concentration of rifampicin
      was measured by UV spectroscopic method. To investigate the effect of solvent on
      transformation, the transformation experiments were carried out in 3 solvents.
      Furthermore, a mathematical model was built to describe the kinetics of
      dissolution, nucleation, and growth processes during transformation by using
      experimental data. By combination of experimental and simulation results, it was
      found that the transformation process of rifampicin is controlled by dissolution
      of form II in heptane, whereas the transformation in hexane and octane was
      firstly controlled by dissolution of solid-state form and then controlled by
      growth of form I.

PMID- 29031975
TI  - New Polymorph Form of Dexamethasone Acetate.
AB  - A new monohydrated polymorph of dexamethasone acetate was crystallized and its
      crystal structure characterized. The different analytical techniques used for
      describing its structural and vibrational properties were: single crystal and
      polycrystal X-ray diffraction, solid state nuclear magnetic resonance, infrared
      spectroscopy. A Hirshfeld surface analysis was carried out through self
      arrangement cemented by H-bonds observed in this new polymorph. This new
      polymorph form appeared because of self-arrangement via classical hydrogen bonds
      around the water molecule.

PMID- 29031976
TI  - Understanding Protein-Interface Interactions of a Fusion Protein at Silicone Oil
      Water Interface Probed by Sum Frequency Generation Vibrational Spectroscopy.
AB  - Protein adsorbed at the silicone oil-water interface can undergo a conformational
      change that has the potential to induce protein aggregation on storage.
      Characterization of the protein structures at interface is therefore critical for
      understanding the protein-interface interactions. In this article, we have
      applied sum frequency generation (SFG) spectroscopy for studying the secondary
      structures of a fusion protein at interface and the surfactant effect on protein
      adsorption to silicone oil-water interface. SFG and chiral SFG spectra from
      adsorbed protein in the amide I region were analyzed. The presence of beta-sheet
      vibrational band at 1635 cm-1 implies the protein secondary structure was likely
      perturbed when protein adsorbed at silicone oil interface. The time-dependent SFG
      study showed a significant reduction in the SFG signal of preadsorbed protein
      when polysorbate 20 was introduced, suggesting surfactant has stronger
      interaction with the interface leading to desorption of protein from the
      interface. In the preadsorbed surfactant and a mixture of protein/polysorbate 20,
      SFG analysis confirmed that surfactant can dramatically prevent the protein
      adsorption to silicone oil surface. This study has demonstrated the potential of
      SFG for providing the detailed molecular level understanding of protein
      conformation at interface and assessing the influence of surfactant on protein
      adsorption behavior.

PMID- 29031977
TI  - Modeling and Prediction of Drug Dispersability in Polyvinylpyrrolidone-Vinyl
      Acetate Copolymer Using a Molecular Descriptor.
AB  - The expansion of a novel in silico model for the prediction of the dispersability
      of 18 model compounds with polyvinylpyrrolidone-vinyl acetate copolymer is
      described. The molecular descriptor R3m (atomic mass weighted 3rd-order
      autocorrelation index) is shown to be predictive of the formation of amorphous
      solid dispersions at 2 drug loadings (15% and 75% w/w) using 2 preparation
      methods (melt quenching and solvent evaporation using a rotary evaporator).
      Cosolidified samples were characterized using a suite of analytical techniques,
      which included differential scanning calorimetry, powder X-ray diffraction, pair
      distribution function analysis, polarized light microscopy, and hot stage
      microscopy. Logistic regression was applied, where appropriate, to model the
      success and failure of compound dispersability in polyvinylpyrrolidone-vinyl
      acetate copolymer. R3m had combined prediction accuracy greater than 90% for
      tested samples. The usefulness of this descriptor appears to be associated with
      the presence of heavy atoms in the molecular structure of the active
      pharmaceutical ingredient, and their location with respect to the geometric
      center of the molecule. Given the higher electronegativity and atomic volume of
      these types of atoms, it is hypothesized that they may impact the molecular
      mobility of the active pharmaceutical ingredient, or increase the likelihood of
      forming nonbonding interactions with the carrier polymer.

PMID- 29031978
TI  - Monitoring the Phase Behavior of Supersaturated Solutions of Poorly Water-Soluble
      Drugs Using Fluorescence Techniques.
AB  - Phase transformations of poorly water-soluble drugs, in low concentration,
      supersaturated aqueous solutions are of considerable interest. Herein,
      fluorescence lifetime and steady-state fluorescence spectroscopy were employed to
      investigate the fluorescence properties of the autofluorescent compound,
      felodipine (a 1,4-dihydropyridine calcium channel blocker), when present as free
      drug in solution, drug-rich aggregates, and crystals. Measurements were also
      performed in the absence and presence of liver microsomes. To study
      nonfluorescent drugs, an environment-sensitive fluoroprobe, 6-propionyl-2
      dimethylaminonaphthalene, was employed. The lifetime of free felodipine in
      solution in simple media was found to be ~0.4 ns, whereas felodipine present in
      drug-rich aggregates and crystals was characterized by a longer lifetime of ~2
      and ~9 ns, respectively. In the presence of structures containing lipids, the
      local environment of felodipine was found to change based on fluorescence
      characteristics and the concentration where felodipine aggregates formed was
      greatly increased. The lifetime of 6-propionyl-2-dimethylaminonaphthalene in
      solutions containing clotrimazole (an imidazole derivative with antimycotic
      activity) or efavirenz (a non-nucleoside reverse transcriptase inhibitor with
      antiviral activity) increased on aggregate formation as a result of the change in
      polarity of the probe local environment. Fluorescence lifetime coupled with
      steady-state fluorescence spectroscopy was demonstrated to be effective in
      identifying the concentration where drug aggregates formed, contributing to
      improved understanding of the phase behavior of poorly water-soluble drugs in
      biologically relevant media.

PMID- 29031979
TI  - Doxorubicin-loaded micelles of amphiphilic diblock copolymer with pendant dendron
      improve antitumor efficacy: In vitro and in vivo studies.
AB  - Previously reported amphiphilic diblock copolymer with pendant dendron moieties
      (P71D3) has been further evaluated in tumor-bearing mice as a potential drug
      carrier. This P71D3-based micelle of an average diameter of 100nm was found to be
      biocompatible, non-toxic and physically stable in colloidal system up to 15days.
      It enhanced the in vitro potency of doxorubicin (DOX) in 4T1 breast tumor cells
      by increasing its uptake, by 3-fold, compared to free DOX. In 4T1 tumor-bearing
      mice, the tumor growth rate of P71D3/DOX (2mg/kg DOX equivalent) treated group
      was significantly delayed and their tumor volume was significantly reduced by 1.5
      fold compared to those treated with free DOX. The biodistribution studies
      indicated that P71D3/DOX enhanced accumulation of DOX in tumor by 5- and 2-fold
      higher than free DOX treated mice at 15min and 1h post-administration,
      respectively. These results suggest that P71D3 micelle is a promising nanocarrier
      for chemotherapeutic agents.

PMID- 29031980
TI  - Quality by Design (QbD) approach to optimize the formulation of a bilayer
      combination tablet (Telmiduo(r)) manufactured via high shear wet granulation.
AB  - A bilayer tablet, which consisted of telmisartan and amlodipine besylate, was
      formulated based on a Quality by Design (QbD) approach. The control and response
      factors were determined based on primary knowledge and the target values of the
      control tablet (Twynsta(r)). A D-optimal mixture design was used to obtain the
      optimal formulations in terms of D-mannitol, crospovidone, and MCC for the
      telmisartan layer, and CCM-Na, PVP K25, and Prosolv for the amlodipine layer. The
      quantitative effects of the different formulation factors on the response factors
      were accurately predicted using the equations of best fit and a strong linearity
      was observed between the predicted and actual values of the response factors. The
      optimized bilayer tablet was obtained using a numeric optimization technique and
      was characterized compared with a control (Twynsta(r)) by using various physical
      evaluations and in vivo pharmacokinetic parameters. The physical stability of
      Telmiduo(r) was greater than that of Twynsta(r) owing to the improvement of
      formulation factors. The in vivo pharmacokinetic parameters suggested that
      Telmiduo(r) might have pharmaceutical equivalence and bioequivalence with
      Twynsta(r). Therefore, the bilayer tablet that consisted of telmisartan and
      amlodipine besylate could be produced using a more economical and simpler method
      than that used to produce Twynsta(r). Moreover, the suitability of QbD for
      effective product development in the pharmaceutical industry was shown.

PMID- 29031981
TI  - Fabrication and characterization of gefitinib-releasing polyurethane foam as a
      coating for drug-eluting stent in the treatment of bronchotracheal cancer.
AB  - The purpose of the present study was to develop gefitinib-loaded polymeric foams
      that can be used as coating of drug-eluting stents for palliative treatment of
      bronchotracheal cancer. Release of such an anticancer drug from such stent
      coating can retard tumor regrowth into the bronchial lumen. Gefitinib-loaded
      polyurethane (PU) foams were prepared by embedding either gefitinib micronized
      crystals or gefitinib-loaded poly(lactic-co-glycolic acid) microspheres in water
      blown films, with up to 10% w/w loading for gefitinib microcrystals and 15% w/w
      for gefitinib microspheres (corresponding to 1.0% w/w drug loading). Drug-release
      studies showed sustained release of gefitinib over a period of nine months, with
      higher absolute release rates at higher drug loading content. By the end of the
      studied nine month release periods, 60-100% of the loaded gefitinib had been
      released. Foams loaded with gefitinib-PLGA microspheres at 15% w/w showed
      accelerated drug release after 4 months, coinciding with the degradation of PLGA
      microparticles in the PU foam as demonstrated by scanning electron microscopy
      (SEM). When applied on a nitinol braided bronchotrachial stent, PU coatings with
      gefitinib microspheres showed similar mechanical properties as the drug-free PU
      coating, which indicated that the loading of microspheres did not affect the
      mechnical properties of the PU foams. In conclusion, we have fabricated drug
      loaded PU foams that are suitable for bronchotracheal stent coating.

PMID- 29031982
TI  - Functionalized hBN as targeted photothermal chemotherapy for complete eradication
      of cancer cells.
AB  - The development of combined anticancer therapeutic techniques has drawn increased
      attention for enhanced therapeutic efficacy. In this work, we synthesized Near
      Infrared (NIR) responsive ICG (I) functionalized hexagonal boron-nitride (hBN) as
      photothermal therapeutic agent (hBNI) and Doxorubicin (Dox)-conjugated Hyaluronic
      acid (HA) as tumor targeted chemotherapeutic agent (d-HA-Dox). Using adhesion
      properties of Dopamine (d), the hBNI has been integrated with d-HA-Dox to make a
      tumor targeted photothermal chemotherapeutic agent (hBNI/d-HA-Dox). The
      nanostructure of hBNI/d-HA-Dox has been studied using 1H NMR, FTIR, UV-vis-NIR
      and AFM images. Our in vitro results have provided evidence that hBNI/d-HA-Dox
      can efficiently damage targeted cancer cells while healthy cells are less
      affected suggesting that the targeted hBNI/d-HA-Dox nanoparticles work as a
      complementary antitumor agent with its synergistic co-therapeutic power.

PMID- 29031983
TI  - Specific Ultrasound Data Acquisition for Tissue Motion and Strain Estimation:
      Initial Results.
AB  - Ultrasound applications such as elastography can benefit from 3-D data
      acquisition and processing. In this article, we describe a specific ultrasound
      probe, designed to acquire series of three adjacent imaging planes over time.
      This data acquisition makes it possible to consider the out-of-plane motion that
      can occur at the central plane during medium scanning, and is proposed with the
      aim of improving the results of strain imaging. In this first study, experiments
      were conducted on phantoms, and controlled axial and elevational displacements
      were applied to the probe using a motorized system. Radiofrequency ultrasound
      data were acquired at a 40-MHz sampling frequency with an Ultrasonix ultrasound
      scanner, and processed using a 3-D motion estimation method. For each of the 2-D
      regions of interest of the central plane in pre-compression data, a 3-D search
      was run to determine its corresponding version in post-compression data, with
      this search taking into account the region-of-interest deformation model chosen.
      The results obtained with the proposed ultrasound data acquisition and strain
      estimation were compared with results from a classic approach and illustrate the
      improvement produced by considering the medium's local displacements in
      elevation, with notably an increase in the mean correlation coefficients
      achieved.

PMID- 29031984
TI  - Analysis of Carotid Artery Transverse Sections in Long Ultrasound Video
      Sequences.
AB  - Examination of the common carotid artery (CCA) based on an ultrasound video
      sequence is an effective method for detecting cardiovascular diseases. Here, we
      propose a video processing method for the automated geometric analysis of CCA
      transverse sections. By explicitly compensating the parasitic phenomena of global
      movement and feature drift, our method enables a reliable and accurate estimation
      of the movement of the arterial wall based on ultrasound sequences of arbitrary
      length and in situations where state-of-the-art methods fail or are very
      inaccurate. The method uses a modified Viola-Jones detector and the Hough
      transform to localize the artery in the image. Then it identifies dominant
      scatterers, also known as interest points (IPs), whose positions are tracked by
      means of the pyramidal Lucas-Kanade method. Robustness to global movement and
      feature drift is achieved by a detection of global movement and subsequent IP re
      initialization, as well as an adaptive removal and addition of IPs. The
      performance of the proposed method is evaluated using simulated and real
      ultrasound video sequences. Using the Harris detector for IP detection, we
      obtained an overall root-mean-square error, averaged over all the simulated
      sequences, of 2.16 +/- 1.18 px. The computational complexity of our method is
      compatible with real-time operation; the runtime is about 30-70 ms/frame for
      sequences with a spatial resolution of up to 490 * 490 px. We expect that in
      future clinical practice, our method will be instrumental for non-invasive early
      stage diagnosis of atherosclerosis and other cardiovascular diseases.

PMID- 29031985
TI  - Spatial Angular Compounding Technique for H-Scan Ultrasound Imaging.
AB  - H-Scan is a new ultrasound imaging technique that relies on matching a model of
      pulse-echo formation to the mathematics of a class of Gaussian-weighted Hermite
      polynomials. This technique may be beneficial in the measurement of relative
      scatterer sizes and in cancer therapy, particularly for early response to drug
      treatment. Because current H-scan techniques use focused ultrasound data
      acquisitions, spatial resolution degrades away from the focal region and
      inherently affects relative scatterer size estimation. Although the resolution of
      ultrasound plane wave imaging can be inferior to that of traditional focused
      ultrasound approaches, the former exhibits a homogeneous spatial resolution
      throughout the image plane. The purpose of this study was to implement H-scan
      using plane wave imaging and investigate the impact of spatial angular
      compounding on H-scan image quality. Parallel convolution filters using two
      different Gaussian-weighted Hermite polynomials that describe ultrasound
      scattering events are applied to the radiofrequency data. The H-scan processing
      is done on each radiofrequency image plane before averaging to get the angular
      compounded image. The relative strength from each convolution is color-coded to
      represent relative scatterer size. Given results from a series of phantom
      materials, H-scan imaging with spatial angular compounding more accurately
      reflects the true scatterer size caused by reductions in the system point spread
      function and improved signal-to-noise ratio. Preliminary in vivo H-scan imaging
      of tumor-bearing animals suggests this modality may be useful for monitoring
      early response to chemotherapeutic treatment. Overall, H-scan imaging using
      ultrasound plane waves and spatial angular compounding is a promising approach
      for visualizing the relative size and distribution of acoustic scattering
      sources.

PMID- 29031986
TI  - Endovascular Interventions for Femoropopliteal Peripheral Artery Disease: A
      Network Meta-Analysis of Current Technologies.
AB  - PURPOSE: To use network meta-analysis (NMA) to determine the optimal endovascular
      strategy for management of femoropopliteal peripheral artery disease (PAD) given
      the lack of multiple prospective randomized trials to guide treatment decisions.
      MATERIALS AND METHODS: NMA is a new meta-analytic method that permits comparisons
      among any 2 therapies by combining results of a collection of clinical trials
      conducted in the same or similar patient population. NMA was used to analyze data
      from 15 randomized controlled trials (RCTs) and 10 prospective, multicenter,
      single-arm trials (combined evidence [CE] NMA) that evaluated target lesion
      revascularization (TLR) for 5 endovascular strategies: bare metal stent (BMS),
      polymer-covered metal stent (CMS), drug-eluting stent (DES), drug-coated balloon
      (DCB) and percutaneous transluminal angioplasty (PTA). RESULTS: The RCT and CE
      NMAs included 2,912 (6,091) patients with 3,151 (6,786) person-years of follow
      up. In the CE NMA, DCB provided a statistically significant 68% reduction in TLR
      compared with PTA and a statistically significant 53% reduction in TLR compared
      with BMS. BMS, CMS, and DES provided reductions in TLR of 33%, 48%, and 58%
      compared with PTA, with statistical significance achieved for CMS and DES. The
      significant reductions in TLR for DCB compared with PTA and BMS were replicated
      in the RCT NMA. CONCLUSIONS: This NMA demonstrated that DCB provided better
      reduction in TLR rates compared with PTA and BMS.

PMID- 29031987
TI  - Intra-articular Injection of Mesenchymal Stem Cells and Platelet-Rich Plasma to
      Treat Patellofemoral Osteoarthritis: Preliminary Results of a Long-Term Pilot
      Study.
AB  - PURPOSE: To assess the feasibility and safety of concomitant intra-articular (IA)
      knee injection of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP)
      under fluoroscopic guidance to treat patellofemoral osteoarthritis (OA).
      MATERIALS AND METHODS: This prospective study included 19 consecutive patients
      referred for fluoroscopically guided IA MSC and PRP injection for symptomatic
      patellofemoral chondropathy in which conservative treatment had failed. Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and magnetic
      resonance (MR) data, including T2 mapping sequence, were prospectively collected
      before and 6 months after treatment. Clinical data without MR imaging were
      collected until 12 months after the procedure. RESULTS: WOMAC scores were
      significantly lower after IA injection of MSCs and PRP at 6 months and during 12
      months follow-up compared with baseline (mean score decreased from 34.3 to 14.2;
      P < .0018). Patients reported no complications. Concerning MR imaging follow-up,
      there were no significant differences in grade, surface, or T2 value of the
      chondral lesions (P > .375). CONCLUSIONS: IA injection of MSCs and PRP in early
      patellofemoral OA appears to allow functional improvement.

PMID- 29031988
TI  - New trends in childhood vision impairment in a developed country.
AB  - BACKGROUND: The Education Vision Assessment Clinic (EVAC) is a unique statewide
      service that reviews school children 4-18 years of age with low vision in
      Victoria, Australia, to determine their eligibility for educational support. The
      purpose of this study was to identify causes of vision impairment in students in
      Victoria using data from the EVAC. METHODS: Data collected from students who
      attended the EVAC at the Royal Victorian Eye and Ear Hospital, Melbourne, between
      the years 2003 and 2012 inclusive, were analyzed retrospectively. Participants
      were identified through the EVAC schedule of medical appointments. Medical
      records were reviewed for clinical and demographic information, including
      diagnosis of vision impairment and best-corrected visual acuity and/or visual
      fields. RESULTS: Of 543 students, 355 (65%) were eligible for educational
      assistance. Of those, 249 (70%) had best-corrected visual acuity between 20/60
      and 20/200 and/or a field of vision of <20 degrees  to 10 degrees , and 106 (30%)
      had a best-corrected visual acuity worse than 20/200 and/or a field of vision of
      <10 degrees . Common causes of vision impairment were retinal dystrophies (24%),
      optic nerve pathology (14%), albinism (14%), and infantile motor nystagmus (10%).
      CONCLUSIONS: Treatable and potentially preventable causes of vision impairment,
      such as retinopathy of prematurity and cataract, caused <10% of vision impairment
      cases in Victorian school children. Analysis of demographic trends is essential
      to supporting efforts to ensure that students with low vision, from any
      socioeconomic background, receive specialist teaching services.

PMID- 29031989
TI  - CHN1 gene mutation analysis in patients with Duane retraction syndrome.
AB  - PURPOSE: To investigate CHN1 (chimerin 1) gene mutations in patients with
      isolated nonsyndromic Duane syndrome and accompanying positive familial history,
      bilaterality, or various systemic disorders. METHODS: Patients with Duane
      retraction syndrome (DRS) and a positive family history of congenital ocular
      motility disturbance or bilateral involvement or accompanying any congenital
      disorder(s) seen consecutively at a single center from 2013 to 2016 were
      enrolled. All subjects underwent full ophthalmologic examination, including
      refraction, best-corrected visual acuity, ocular alignment and motility, globe
      retraction, and biomicroscopic or fundus evaluation. DNA samples were
      investigated by direct sequencing of the coding regions of the CHN1 gene.
      RESULTS: A total of 30 patients (15 males) were included (mean age, 11.8 +/- 10.4
      years; range, 2-45 years): 8 cases presented with bilateral DRS; 22, with
      unilateral DRS. Family history of ocular motility abnormality was positive in 16
      patients. Eleven cases had an additional congenital disorder. In 2 patients, 2
      different mutations were detected in the CHN1 gene: p.E313K (c.937G>A) and
      p.N224S (c.671A>G). CONCLUSIONS: CHN1 mutations were identified in 2 bilateral
      cases and in 1 parent of 1 affected case. One mutation is novel and occurred with
      additional vertical gaze abnormalities. Additional genetic studies evaluating
      chimerin 1 (CHN1) and its role in the development of the ocular motor axis are
      needed to provide new data about these mutations and phenotypic variations.

PMID- 29031990
TI  - International standardization of diagnostic criteria for microvascular angina.
AB  - Standardization of diagnostic criteria for ischemic symptoms due to coronary
      microvascular dysfunction (CMD) is needed for further investigation of patients
      presenting with anginal chest pain consistent with "microvascular angina" (MVA).
      At the annual Coronary Vasomotion Disorders International Study Group (COVADIS)
      Summits held in August 2014 and 2015, the following criteria were agreed upon for
      the investigative diagnosis of microvascular angina: (1) presence of symptoms
      suggestive of myocardial ischemia; (2) objective documentation of myocardial
      ischemia, as assessed by currently available techniques; (3) absence of
      obstructive CAD (<50% coronary diameter reduction and/or fractional flow reserve
      (FFR) >0.80) (4) confirmation of a reduced coronary blood flow reserve and/or
      inducible microvascular spasm. These standardized criteria provide an
      investigative structure for mechanistic, diagnostic, prognostic and clinical
      trial studies aimed at developing an evidence base needed for guidelines in this
      growing patient population. Standardized criteria will facilitate microvascular
      angina registries and recruitment of suitable patients into clinical trials.
      Mechanistic research will also benefit from the implementation of standardized
      diagnostic criteria for MVA.

PMID- 29031991
TI  - Preoperative Toxoplasma gondii serostatus does not affect long-term survival of
      cardiac transplant recipients. Analysis of the Spanish Heart Transplantation
      Registry.
AB  - BACKGROUND: It's unclear whether pre-transplant T. gondii seropositivity is
      associated with impaired survival in heart transplant recipients. OBJECTIVES: To
      test the above-mentioned hypothesis in the Spanish Heart Transplantation
      Registry. METHODS: Post-transplant outcomes of 4048 patients aged >16years who
      underwent first, single-organ heart transplantation in 17 Spanish institutions
      from 1984 to 2014 were studied. Long-term post-transplant survival and survival
      free of cardiac death or retransplantation of 2434 (60%) T. gondii seropositive
      recipients and 1614 (40%) T. gondii seronegative recipients were compared.
      RESULTS: T. gondii seropositive recipients were older, had higher body mass
      index, and presented higher prevalence of hypertension, hypercholesterolemia,
      COPD and Cytomegalovirus seropositivity than T. gondii seronegative recipients.
      In univariable analysis, pre-transplant T. gondii seropositivity was associated
      with increased post-transplant all-cause mortality (non-adjusted HR 1.15; 95% CI
      1.04-1.26). However, this effect was no longer statistically significant after
      multivariable adjustment by recipient's age and sex (adjusted HR 1.01, 95% CI
      0.92-1.11). Extended multivariable adjustment by other potential confounders
      showed similar results (adjusted HR 0.99, 95% CI 0.89-1.11). T. gondii
      seropositivity had no significant effect on the composite outcome cardiac death
      or retransplantation (non-adjusted HR 1.08, 95% CI 0.95-1.24, p=0.235). The
      distribution of the causes of death was comparable in T. gondii seropositive and
      T. gondii seronegative recipients. No statistically significant impact of donor's
      T. gondii serostatus or donor-recipient T. gondii serostatus matching on post
      transplant survival was observed. CONCLUSIONS: Our analysis did not show a
      significant independent effect of preoperative T. gondii serostatus on long-term
      outcomes after heart transplantation.

PMID- 29031992
TI  - Assessing the utility of a prognostication model to predict 1-year mortality in
      patients undergoing radiation therapy for spinal metastases.
AB  - BACKGROUND CONTEXT: Predicting survival outcomes after radiation therapy (RT)
      alone for metastatic disease of the spine is a challenging task that is important
      to guiding treatment decisions (eg, determining dose fractionation and
      intensity). The New England Spinal Metastasis Score (NESMS) was recently
      introduced and validated in independent cohorts as a tool to predict 1-year
      survival following surgery for spinal metastases. This metric is composed of
      three factors: preoperative albumin, ambulatory status, and modified Bauer score,
      with the total score ranging from 0 to 3. PURPOSE: The purpose of this study was
      to assess the applicability of the NESMS model to predict 1-year survival among
      patients treated with RT alone for spinal metastases. STUDY DESIGN/SETTING: This
      study is a retrospective analysis. PATIENT SAMPLE: This sample included 290
      patients who underwent conventional RT alone for spinal metastases. OUTCOME
      MEASURES: Patients' NESMS (composed of ambulatory status, pretreatment serum
      albumin, and modified Bauer score) were assessed, as well as their 1-year overall
      survival rates following radiation for metastatic disease of the spine. MATERIALS
      AND METHODS: This study is a single-institution retrospective analysis of 290
      patients treated with conventional radiation alone for spinal metastases from
      2008 to 2013. The predictive value of the NESMS was assessed using multivariable
      logistic regression modeling, adjusted for potential confounding variables.
      RESULTS: This analysis indicated that patients with lower NESMSs had higher rates
      of 1-year mortality. Multivariable analysis demonstrated a strong association
      between lower NESMSs and lower rates of survival. CONCLUSIONS: The NESMS is a
      simple prognostic scheme that requires clinical data that are often readily
      available and have been validated in independent cohorts of surgical patients.
      This study serves to validate the utility of the NESMS composite score to predict
      1-year mortality in patients treated with radiation alone for spinal metastases.

PMID- 29031993
TI  - The GDF5 mutant BB-1 enhances the bone formation induced by an injectable, poly(l
      lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming cement in a
      sheep defect model of lumbar osteopenia.
AB  - BACKGROUND CONTEXT: Targeted delivery of osteoinductive bone morphogenetic
      proteins (eg, GDF5) in bioresorbable calcium phosphate cement (CPC), potentially
      suitable for vertebroplasty and kyphoplasty of osteoporotic vertebral fractures,
      may be required to counteract augmented local bone catabolism and to support
      complete bone regeneration. The biologically optimized GDF5 mutant BB-1 may
      represent an attractive drug candidate for this purpose. PURPOSE: The aim of the
      current study was to test an injectable, poly(l-lactide-co-glycolide) acid (PLGA)
      fiber-reinforced, brushite-forming CPC containing low-dose BB-1 in a sheep lumbar
      osteopenia model. STUDY DESIGN/ SETTING: This is a prospective experimental
      animal study. METHODS: Bone defects (diameter 5 mm) were generated in aged,
      osteopenic female sheep and were filled with fiber-reinforced CPC alone (L4;
      CPC+fibers) or with CPC containing different dosages of BB-1 (L5; CPC+fibers+BB
      1; 5, 100, and 500 ug BB-1; n=6 each). The results were compared with those of
      untouched controls (L1). Three and 9 months after the operation, structural and
      functional effects of the CPC (+/-BB-1) were analyzed ex vivo by measuring (1)
      bone mineral density (BMD); (2) bone structure, that is, bone volume/total volume
      (BV/TV) (assessed by micro-CT and histomorphometry), trabecular thickness
      (Tb.Th), and trabecular number (Tb.N); (3) bone formation, that is, osteoid
      volume/bone volume (OV/BV), osteoid surface/bone surface (OS/BS), osteoid
      thickness, mineralizing surface/bone surface (MS/BS), mineral apposition rate,
      and bone formation rate/bone surface; (4) bone resorption, that is, eroded
      surface/bone surface; and (5) compressive strength. RESULTS: Compared with
      untouched controls (L1), CPC+fibers (L4) and/or CPC+fibers+BB-1 (L5)
      significantly improved all parameters of bone formation, bone resorption, and
      bone structure. These effects were observed at 3 and 9 months, but were less
      pronounced for some parameters at 9 months. Compared with CPC without BB-1,
      additional significant effects of BB-1 were demonstrated for BMD, bone structure
      (BV/TV, Tb.Th, and Tb.N), and bone formation (OS/BS and MS/BS). The BB-1 effects
      on bone formation at 3 and 9 months were dose dependent, with 100 ug as the
      potentially optimal dosage. CONCLUSIONS: BB-1 significantly enhanced the bone
      formation induced by a PLGA fiber-reinforced CPC in sheep lumbar osteopenia. A
      single local dose as low as 100 ug BB-1 was sufficient to augment middle- to long
      term bone formation. A CPC containing the novel GDF5 mutant BB-1 may thus
      represent an alternative to the bioinert, supraphysiologically stiff
      polymethylmethacrylate cement presently used to treat osteoporotic vertebral
      fractures by vertebroplasty and kyphoplasty.

PMID- 29031994
TI  - Clinical classification criteria for neurogenic claudication caused by lumbar
      spinal stenosis. The N-CLASS criteria.
AB  - BACKGROUND CONTEXT: Because imaging findings of lumbar spinal stenosis (LSS) may
      not be associated with symptoms, clinical classification criteria based on
      patient symptoms and physical examination findings are needed. PURPOSE: The
      objective of this study was to develop clinical classification criteria that
      identify patients with neurogenic claudication (NC) caused by LSS. STUDY DESIGN:
      This study is a two-stage process that includes Phase 1, the Delphi process, and
      Phase 2, the cross-sectional study. PATIENT SAMPLE: Outpatients were recruited
      from spine clinics in five countries. OUTCOME MEASURE: The outcome measure
      includes items from the patients' history and physical examination. METHODS: In
      Phase 1, a list of potential predictors of NC caused by LSS was based on the
      available literature and was evaluated through a Delphi process involving 17
      spine specialists (surgeons and non-surgeons) from eight countries. In Phase 2,
      19 different clinical spine specialists from five countries identified patients
      they classified as having (1) NC caused by LSS, (2) radicular pain caused by
      lumbar disc herniation (LDH), or (3) non-specific low back pain (NSLBP) with
      radiating leg pain. The patients completed survey items and the specialists
      documented the examination signs. Coefficients from general estimating equation
      models were used to select predictors, to generate a clinical classification
      score, and to obtain a receiver operating characteristic curve. Conduction of the
      Delphi process, data management, and statistical analysis were partially
      supported by an unrestricted grant of less than 15,000 US dollars from Merck
      Sharp & Dohme. No fees were allocated to participating spine specialists.
      RESULTS: Phase 1 generated a final list of 46 items related to LSS. In Phase 2,
      209 patients with leg pain caused by LSS (n=63), LDH (n=89), or NSLBP (n=57) were
      included. Criteria that independently predicted NC (p<.05) were age over 60
      years, positive 30-second extension test, negative straight leg test, pain in
      both legs, leg pain relieved by sitting, and leg pain decreased by leaning
      forward or flexing the spine. A classification score using a weighted set of
      these criteria was developed. The proposed N-CLASS score ranged from 0 to 19 and
      had an area under the curve of 0.92, and the cutoff (>10/19) to obtain a
      specificity of >90.0% resulted in a sensitivity of 82.0%. CONCLUSIONS: Clinical
      criteria independently associated with neurogenic claudication due to LSS were
      identified. The use of these symptom and physical variables as a classification
      score for clinical research could improve homogeneity among enrolled patients.

PMID- 29031995
TI  - Comparison of deproteinization agents on bonding to developmentally
      hypomineralized enamel.
AB  - OBJECTIVE: To compare bonding of dental adhesive to hypomineralized enamel (HE)
      after pre-treatment with either 5% sodium hypochlorite (NaOCl) solution or papain
      based papacarie gel. METHODS: Normal enamel (NE) and HE obtained from
      hypomineralized first permanent molars were acid-etched with 32% phosphoric acid
      and randomly allocated into no deproteinization, deproteinization using 5% NaOCl,
      or deproteinization usping papacarie gel groups. Subsequently, the specimens were
      bonded, packed with composite resins and subjected to micro-shear bond strength
      (MSBS) testing and the data analysed using 2-way ANOVA and Tukey tests.
      Furthermore, specimens from all groups were subjected for qualitative analysis
      using scanning electron microscope. RESULTS: Two way-ANOVA showed that the factor
      "enamel substrate" was significant (p<0.001), "enamel pre-treatment" was not
      significant and interaction of the two factors was significant (p=0.005). HE
      produced inferior bonding with dental adhesive compared to NE. Enamel pre
      treatment with deproteinization agents enhanced bonding to HE. No significant
      difference in MSBS was evident between the two deproteinization agents (p>0.05).
      Qualitative analysis of acid-etched moderate HE showed barely visible enamel rods
      with irregular etching pattern. Following acid etching and deproteinization, Type
      I and II etching patterns were observed in moderate HE; while a porous enamel
      surface with more profound etching patterns in severe HE. CONCLUSIONS: Papain
      based papacarie could be an alternative deproteinization agent for bonding dental
      adhesive to HE. CLINICAL SIGNIFICANCE: Papain-based papacarie, a natural
      deproteinization agent and a proven chemo-mechanical caries removal agent could
      be an alternative to NaOCl for enhancement of bond durability of adhesive
      restorations to HE.

PMID- 29031996
TI  - Assessing the quality of dental clinical practice guidelines.
AB  - OBJECTIVES: The primary aim of this study was to evaluate the quality of
      published dental clinical guidelines using the AGREE II instrument. METHODS:
      Online searching of a wide range of organisations (national and International)
      was undertaken to identify dental clinical practice guidelines published between
      2000 and 2014. The quality of each included guideline was assessed in relation to
      the AGREE II instrument by four assessors independently. Inter-rater agreement
      was assessed. Descriptive statistics and both univariate and multivariate
      analyses were conducted. RESULTS: 162 guidelines were identified. The overall
      mean quality score was 51.9% (SD 13.3). There was variation in the reporting
      quality of individual domains with both Applicability (20.4%) and Editorial
      Independence (34.25%) poorly reported. Variation between the overall quality
      scores for guidelines produced by different dental specialities was evident. The
      quality of guidelines improved per publication year (beta=0.76, 95% CI: 0.26,
      1.26, p=0.003). Guidelines based on formal evidence (beta=19.94, 95% CI: 15.25,
      24.64, p=0.001) achieved higher quality scores. CONCLUSION: Overall, the quality
      of clinical dental practice guidelines is suboptimal. There is variation in the
      overall quality, reporting of individual items and domains of the AGREE II
      instrument between different dental speciality clinical practice guidelines.
      Guidelines based on formal evidence achieved higher quality scores. CLINICAL
      SIGNIFICANCE: Clinicians should be aware of the variation in the quality of
      dental clinical guidelines in particular related to methodological rigour. The
      use of formal evidence may be a useful indicator of their quality prior to their
      implementation.

PMID- 29031997
TI  - A six-year longitudinal PET study of (+)-[11C]DTBZ binding to the VMAT2 in monkey
      brain.
AB  - INTRODUCTION: The longitudinal reproducibility of in vivo binding potential
      measures for [11C]dihydrotetrabenazine ([11C]DTBZ) binding to the vesicular
      monoamine transporter 2 (VMAT2) site in primate brain was examined using a unique
      dataset of repeated control PET imaging studies. METHODS: Forty-one dynamic
      [11C]DTBZ PET studies were completed in a single rhesus monkey. Imaging equipment
      (microPET P4), personnel, radiotracer characteristics (injected mass amounts,
      molar activity) and image data analysis (BPND-Logan) were consistent throughout
      the entire sequence of PET studies. RESULTS: Same day reproducibility of BPND
      Logan estimates of specific binding was very good (-3% and -7% changes) for two
      control-control sessions. Over the full 74 months, the average BPND-Logan value
      for [11C]DTBZ-PET studies was 4.19+/-0.52, for a variance of 12%. No age
      dependent change in binding potentials was observed over the six-year period.
      CONCLUSIONS: If the technical variables associated with PET scanner are
      consistently maintained, including PET scanner, imaging procedures and
      radiotracer preparation, in vivo biochemistry can be reproducibly measured in the
      primate brain over a multi-year period of time.

PMID- 29031998
TI  - Dominant foot could affect the postural control in vestibular neuritis perceived
      by dynamic body balance.
AB  - During attacks of vestibular neuritis (VN), patients typically lose postural
      balance, with resultant postural inclination, gait deviation toward the lesion
      side, and tendency to fall. In this study, we examined and analyzed static and
      dynamic postural control during attacks of VN to characterize differences in
      postural control between right and left VN. Subjects were patients diagnosed with
      VN at the Department of Otolaryngology, Toho University Sakura Medical Center,
      and underwent in-patient treatment. Twenty-five patients who had spontaneous
      nystagmus were assessed within 3days after the onset; all were right-foot
      dominant. Right VN was detected in nine patients (men: 4, women: 5; mean age:
      57.6+/-17.08years [range: 23-82]) and left VN in 16 patients (men: 10, women: 6;
      mean age: 58.4+/-14.08years [range: 23-85 years]); the percentages of canal
      paresis of right and left VN were 86.88+/-18.1% and 86.02+/-15.0%, respectively.
      Statistical comparisons were conducted using the independent t-test. In
      stabilometry, with eyes opened, no significant differences were found between
      patients with right and left VN. However, with eyes closed, the center of
      horizontal movement significantly shifted ipsilateral (p<0.01). The differences
      in the lateral and anteroposterior body tracking test (BTT) were statistically
      significant (p=0.0039 and p=0.0376, respectively), with greater changes in cases
      with right VN. Thus, the dominant foot might contribute to the postural control
      mechanism.

PMID- 29031999
TI  - Analysis of biases in dynamic margins of stability introduced by the use of
      simplified center of mass estimates during walking and turning.
AB  - The ability to control the body's center of mass (CoM) is critical for preventing
      falls, which are a major health concern in aging populations. Control of the CoM
      has been assessed by characterizing dynamic margins of stability (MoS) which
      capture the dynamic relationship between the CoM and the base of support.
      Accurate estimation of CoM dynamics is best accomplished using a full-body marker
      set. However, a number of simplified estimates have been used throughout
      literature. Here, we determined the biases and sources of bias when computing MoS
      using four simplified CoM models, and we characterized how these biases varied in
      straight walking versus turning. CoM kinematics were characterized using a full
      body marker set, the lower extremities and trunk, lower extremities only, an
      average of four pelvic markers, and one pelvic marker alone. Significant bias was
      demonstrated for most methods and was larger during turning tasks compared to
      straight walking. In the fore-aft direction, only overestimates in the MoS were
      observed, and these ranged from 15 to 110% larger than the true MoS value. In the
      mediolateral direction, both under- and over-estimates were observed and ranged
      from -175 to 225%. Across tasks, bias was smallest when using the lower extremity
      plus trunk (-23 to 62%) and pelvis average methods (-71 to 43%). Sources of bias
      were attributed to misestimates of CoM height, velocity, and position. Together,
      our findings suggest that the 1) lower extremity and trunk model and 2) pelvis
      average model should be considered in future studies to minimize bias when
      simplified models of CoM dynamics are desired.

PMID- 29032000
TI  - Everyday multitasking habits: University students seamlessly text and walk on a
      split-belt treadmill.
AB  - With increasing numbers of adults owning a cell phone, walking while texting has
      become common in daily life. Previous research has shown that walking is not
      entirely automated and when challenged with a secondary task, normal walking
      patterns are disrupted. This study investigated the effects of texting on the
      walking patterns of healthy young adults while walking on a split-belt treadmill.
      Following full adaptation to the split-belt treadmill, thirteen healthy adults
      (23+/-3years) walked on a tied-belt and split-belt treadmill, both with and
      without a simultaneous texting task. Inertial-based movement monitors recorded
      spatiotemporal components of gait and stability. Measures of spatial and temporal
      gait symmetry were calculated to compare gait patterns between treadmill (tied
      belt and split-belt) and between texting (absent or present) conditions. Typing
      speed and accuracy were recorded to monitor texting performance. Similar to
      previous research, the split-belt treadmill caused an alteration to both spatial
      and temporal aspects of gait, but not to time spent in dual support or stability.
      However, all participants successfully maintained balance while walking and were
      able to perform the texting task with no significant change to accuracy or speed
      on either treadmill. From this paradigm it is evident that when university
      students are challenged to text while walking on either a tied-belt or split-belt
      treadmill, without any other distraction, their gait is minimally affected and
      they are able to maintain texting performance.

PMID- 29032001
TI  - Efficacy of self-retained cryopreserved amniotic membrane for treatment of
      neuropathic corneal pain.
AB  - PURPOSE: Treatment of neuropathic corneal pain (NCP) remains intricate, and
      involves a long-term combined multistep approach. The self-retained cryopreserved
      amniotic membrane (PROKERA(r), Bio-Tissue, Miami,FL) has been utilized for
      multiple ocular surface disorders. We evaluate the efficacy, safety, and
      tolerability of ProKera(r) Slim [PKS] and ProKera(r) Clear [PKC] in the treatment
      of NCP. METHODS: Retrospective case series of 9 patients who received PKS/PKC for
      the acute treatment of NCP. Patient demographics, prior therapies, clinical
      examination, duration of PKS/PKC retention, changes in pain severity, corneal
      subbasal nerve density and morphology by in vivo confocal microscopy (IVCM;
      HRT3/RCM, Heidelberg Engineering, Heidelberg, Germany), and adverse events were
      recorded. RESULTS: PKS/PKC were placed in 10 eyes of 9 patients. Pain severity
      improved by 72.5 +/- 8.4% (from 6.3 +/- 0.8 to 1.9 +/- 0.6, scale 1-10, p =
      0.0003) after retention for 6.4 +/- 1.1 days. Despite shorter retention for 4.0
      +/- 0.7 days in patients with ring dysesthesia (4 eyes) or premature implant
      disengagement (2 eyes), pain severity still improved by 63.1 +/- 12.5% (from 6.8
      +/- 1.0 to 2.4 +/- 0.9, p = 0.009). During a follow-up of 9.3 +/- 0.8 months, two
      patients reported recurrence of pain after 2.3 and 9.6 months respectively,
      treated effectively with additional PKS/PKC. IVCM showed a 36.6 +/- 17.6%
      increase in total nerve density, from 17,700.9 +/- 1315.7 to 21,891.3 +/- 2040.5
      MUm/mm2 (p = 0.047), while the fellow PKS/PKC-untreated eyes did not show a
      significant interval change. Main nerve trunk and branch nerve densities were not
      statistically different. Dendritiform cell density decreased from 46.0 +/- 8.2 to
      32.0 +/- 6.0 cells/mm2 (p = 0.01). CONCLUSIONS: PKS/PKC provide a safe and
      effective treatment approach to achieve sustained pain control in patients with
      NCP.

PMID- 29032002
TI  - Recoveries of rare elements Ga, Ge, In and Sn from waste electric and electronic
      equipment through secondary copper smelting.
AB  - The recycling and recovery of valuable metals from waste materials is one of the
      key issues in maintaining the sustainability of base and rare metals. Especially
      WEEE (Waste Electric and Electronic Equipment) can be considered as a high
      potential resource for a number of valuable and critical metals like gallium,
      germanium and indium. During the mechanical processing of WEEE, these metals are
      primary separated into the non-ferrous scrap fractions, including copper
      fraction. As a consequence, the behavior of these valuable metals and the
      possibility of their recycling in secondary copper smelting are of great
      interest. This study experimentally investigates the distribution behavior of
      indium, gallium, germanium and tin between metallic copper and lime-free / lime
      containing alumina iron silicate slags (LCu/s[Me] = [Me]Copper/(Me)Slag), as well
      as between solid Al-Fe spinel and slags (Lsp/s[Me] = {Me}spinel/(Me)slag).
      Moreover, the copper-slag-spinel equilibrium systems are examined. The
      experiments were executed simulating high alumina-bearing copper scrap smelting
      in typical black copper smelting conditions of pO2 = 10-10-10-5 atm (1 atm =
      1.01325 * 105 Pa) and T = 1300  degrees C. The experimental technique employed
      utilized a highly advanced equilibration-rapid quenching method followed by
      Electron Probe Micro-Analysis (EPMA). The results show that tin and indium can be
      efficiently recovered into the copper phase in reducing process conditions (pO2
      below 10-7 atm), whereas gallium dissolved preferentially into the solid spinel
      phase in all conditions examined. Gallium dissolution into slag and spinel was
      found to occur as GaO1.5, whereas indium in spinel was determined to be as
      InO1.5. In addition, germanium was seen to distribute preferentially into the
      copper phase with LCu/s[Ge] = 2-4, although its concentrations in all phases
      present were relatively low. Thus, the main route for germanium can be considered
      to be vaporization.

PMID- 29032003
TI  - Electrodialytic extraction of Cr from water-washed MSWI fly ash by changing pH
      and redox conditions.
AB  - Electrodialytic process offers a range of possibilities to waste management by
      electrodialytic separation (EDS) of heavy metals, depending on how the process is
      designed. Using three EDS cell setups (two two-compartment and one three
      compartment) and their combinations, the extraction of Cr from municipal solid
      waste incineration fly ash by changing pH and redox conditions was investigated
      in the present work. The experiments were designed into single, two and three
      steps, based on the number of setups (by changing EDS cells) or effective setups
      (by shifting working electrode pairs) used. Prior to EDS the ash studied went
      through pretreatments such as water-washing and dry-sieving with a 50 um sieve.
      The results showed that Cr was strongly bound in the ash, and the major fraction
      remained bound after the different treatments. Two/three-step treatment, which
      obtained the maximum Cr extraction rate of 27.5%, is an improvement on the single
      step that extracted maximum 3.1%. The highest extraction was obtained due to the
      combined extraction of Cr(III) under low pH (accompanied with high redox)
      conditions and Cr(VI) under high pH (low redox) conditions subsequently. The Cr
      leaching from the treated ashes with acidic pH was lower than from those with
      alkaline pH; after the three-step treatment, Cr leaching was much lower from the
      coarse fraction (> 50 um), as compared to the fine (<= 50 um) or the unsieved
      ash. As for the coarse fraction, two/three-step treatment reduced the leaching of
      Cr compared to the single-step in the same pH range (either acidic or alkaline).

PMID- 29032004
TI  - TNFR2: A Novel Target for Cancer Immunotherapy.
AB  - Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but
      exhibit variable efficacy and relapse and can induce autoimmunity. Tumor necrosis
      factor (TNF) receptor 2 (TNFR2) is a signaling molecule found on the surface of a
      subset of potent regulatory T cells (Tregs) that can activate the proliferation
      of these cells through nuclear factor kappa B (NF-kappaB). TNFR2 is also
      abundantly expressed on the surface of many human tumors. We propose that
      blocking TNFR2 might target abundant TNFR2+ tumor-infiltrating Tregs and directly
      kill TNFR2-expressing tumors. We also posit that TNFR2 inhibitors might
      potentially constitute safer and more targeted alternatives to ICI cancer
      treatment because the expression of TNFR2 on immune cells, concentrated in the
      tumor microenvironment of various cancers, appears to be more selective than that
      of checkpoint molecules.

PMID- 29032005
TI  - Promoting In Vitro Gametogenesis Research with a Social Understanding.
AB  - Recent advances in in vitro gametogenesis (IVG), including in humans, have raised
      ethical concerns regarding the potential misuse and manipulation of 'artificial
      embryos'. However, basic research on IVG is expected to be of immense scientific
      and social value provided that the ethical, legal, and social issues are
      carefully considered.

PMID- 29032006
TI  - Bi-orifice approach to nasal intubation in children: A case series of anticipated
      difficult airways undergoing orthognathic surgeries.

PMID- 29032007
TI  - The effect of sevoflurane compared to propofol maintenance on post-surgical
      quality of recovery in patients undergoing an ambulatory gynecological surgery: A
      prospective, randomized, double-blinded, controlled, clinical trial.
AB  - OBJECTIVE: The main objective of the current investigation was to evaluate the
      effect of propofol used as anesthetic maintenance compared to sevoflurane on
      global post-surgical quality of recovery in female patients undergoing ambulatory
      gynecological surgery. DESIGN: The study was a prospective randomized double
      blinded, controlled, clinical trial. INTERVENTIONS: Healthy female subjects were
      randomized to receive propofol or sevoflurane as anesthetic maintenance.
      MEASUREMENTS: The primary outcome was the Quality of Recovery 40 (QOR-40)
      questionnaire at 24h after surgery. Other data collected included opioid
      consumption, pain scores and time to hospital discharge. P<0.05 was used to
      reject the null hypothesis for the primary outcome. MAIN RESULTS: Ninety subjects
      were randomized and sixty seven completed the study. Patient's baseline
      characteristics and surgical factors were not different between study groups.
      There was not a clinically significant difference in the global QoR-40 scores
      between the sevoflurane and the propofol groups, median (IQR) of 175 (163 to 181)
      and 176 (163 to 184), respectively, P=0.97. There was an inverse relationship
      (rho=-0.42) between the opioid consumption in PACU (IV morphine equivalents) and
      24h postoperative quality of recovery (P<0.001) and an inverse relationship (rho=
      0.48) between the oral opioid consumption at home (oral morphine equivalents) and
      24h postoperative quality of recovery, P<0.001. CONCLUSIONS: Our current results
      do not support the use of total intravenous anesthesia as an efficacious strategy
      to improve global quality of recovery after ambulatory surgery. Opioid
      consumption in the PACU is an earlier surrogate that can be utilized to identify
      ambulatory patients with a high likelihood to develop poor global quality of
      recovery and who may benefit from more efficacious strategies to improve global
      quality of recovery. TRIAL REGISTRATION: ClinicalTrial.gov; url:
      http://www.clinicaltrials.gov; registration identified: NCT 01755234.

PMID- 29032008
TI  - 3-Iodothyroacetic acid (TA1), a by-product of thyroid hormone metabolism, reduces
      the hypnotic effect of ethanol without interacting at GABA-A receptors.
AB  - 3-iodothyroacetic acid (TA1) is among the by-products of thyroid hormone
      metabolism suspected to mediate the non-genomic effects of the hormone (T3). We
      aim to investigate whether TA1 systemically administered to mice stimulated mice
      wakefulness, an effect already described for T3 and for another T3 metabolite
      (i.e. 3-iodothryonamine; T1AM), and whether TA1 interacted at GABA-A receptors
      (GABA-AR). Mice were pre-treated with either saline (vehicle) or TA1 (1.32, 4 and
      11 MUg/kg) and, after 10 min, they received ethanol (3.5 g/kg, i.p.). In another
      set of experiments, TA1 was administered 5 min after ethanol. The latency of
      sleep onset and the time of sleep duration were recorded. Voltage-clamp
      experiments to evaluate the effect of 1 MUM TA1 on bicuculline-sensitive currents
      in acute rat hippocampal slice neurons and binding experiments evaluating the
      capacity of 1, 10, 100 MUM TA1 to displace [3H]flumazenil from mice brain
      membranes were also performed. 4 MUg/kg TA1 increases the latency of onset and at
      1.32 and 4 MUg/kg it reduces the duration of ethanol-induced sleep only if
      administered before ethanol. TA1 does not functionally interact at GABA-AR.
      Overall these results indicate a further similarity between the pharmacological
      profile of TA1 and that of T1AM.

PMID- 29032009
TI  - Potential for stem cell treatment in manganism.
AB  - Development of manganism (also known as manganese neurotoxicity) is a major
      complication of manganese exposure in which neurological dysfunction is linked to
      accumulation of the metal in brain. Due to neuronal cell death in basal ganglia
      structures, particularly the globus pallidus, functional recovery is limited.
      Bearing a resemblance to Parkinson's disease, effective treatment for manganism
      is currently limited. However, the rapidly developing field of stem cell research
      offers new hope for the treatment of illnesses in which neurodegeneration is a
      major feature. The first part of this review will focus on the clinical features
      and pathophysiology of cerebral damage resulting from exposure to manganese,
      including the role of astrocytes, disruption of energy metabolism, involvement of
      oxidative stress, excitotoxicity, and inflammation, with the second part
      exploring how stem cells may provide an important therapeutic strategy for
      patients with this major neurologic disorder.

PMID- 29032010
TI  - Dual effects of insect nAChR chaperone RIC-3 on hybrid receptor: Promoting
      assembly on endoplasmic reticulum but suppressing transport to plasma membrane on
      Xenopus oocytes.
AB  - Resistance to inhibitors of cholinesterase (RIC) -3 promotes the maturation
      (folding and assembly) of neuronal nicotinic acetylcholine receptors (nAChRs) as
      a molecular chaperone. The modulation effects of RIC-3 on homomeric alpha7 nAChRs
      are always positive, but its effects on heteromeric subtypes are inconsistent
      among reports. In this study, five RIC-3 isoforms were identified from Locusta
      migratoria. Four isoforms showed obvious effects on hybrid receptor
      Localpha1/rbeta2 expressed in Xenopus oocytes. As a representative, the co
      expression of RIC-3v4 exhibited the decreased agonist responses (Imax) on
      oocytes, lower specific [3H]epibatidine binding (Bmax) on plasma membrane protein
      (PMP), and reduced subunit levels in PMP, which showed that the mature
      Localpha1/rbeta2 on the plasma membrane was decreased by the co-expression of RIC
      3. In contrast, the [3H]epibatidine binding and mature Localpha1/rbeta2 levels in
      the endoplasmic reticulum membrane protein (ERMP) were much increased when co
      expressing with RIC-3v4. The [3H]epibatidine binding and mature Localpha1/rbeta2
      levels in total membrane protein (TMP) gave the similar results as that in ERMP.
      Taking data together, the results showed that the co-expression of RIC-3
      increased the mature Localpha1/rbeta2 receptor levels on ER of Xenopus oocytes,
      but these mature receptors were mostly kept on ER and suppressed to transport to
      plasma membrane.

PMID- 29032011
TI  - Sitagliptin enhances the neuroprotective effect of pregabalin against
      pentylenetetrazole-induced acute epileptogenesis in mice: Implication of
      oxidative, inflammatory, apoptotic and autophagy pathways.
AB  - The current investigation aimed at studying the anti-epileptogenic effect of
      sitagliptin. The possible effect of the drug in combination with pregabalin in
      pentylenetetrazole (PTZ)- induced seizures was studied. In addition, the
      postulated mechanisms that could mediate such effect were explored namely,
      suppression of oxidative stress and neuro-inflammatory markers, autophagy and
      apoptosis. Seven days prior to PTZ (60 mg/kg, sc) injection, mice were treated
      with sitagliptin (5, 15, and 60 mg/kg, twice daily, orally) or pregabalin (30
      mg/kg, once daily, orally) or their combination. At the end of the experiment,
      several parameters were assessed including: oxidative/nitro-oxidative stress such
      as superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase
      (GP-x) catalase (CAT), and lipid peroxidation assessed as malondialdehyde (MDA),
      nitrate/nitrite (NOx), 3-nitrotyrosine (3-NT). Seizure latency was evaluated.
      Neuronal damage was also assessed by performing tissue staining by hematoxylin
      and eosin, estimating hippocampus level of glutamate, gamma-aminobutyric acid
      (GABA), glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic
      factor (BDNF). Also, markers for inflammation, autophagy and apoptosis were
      measured, nuclear factor erythroid-derived 2- like 2 (Nrf2), nuclear factor kappa
      B (NF-kappaB), phosphatidylethanolamine-conjugated form of microtubule-associated
      protein light chain-3 (LC3-II), casapase-3, Bcl-2-like protein 4 (BAX) and
      glucagon like peptide-1 (GLP-1) activity. Sitagliptin significantly suppressed
      epileptogenesis in PTZ-induced seizures. Sitagliptin counteracted neuronal damage
      and all biochemical, and histo-chemical alteration induced by PTZ. Also, a more
      significant protective effect was observed after combination with pregabalin.
      This study is indicative for the antiepileptogenic potential of sitagliptin with
      or without pregabalin in the PTZ model of epilepsy which is likely to be through
      its effect on antioxidant, anti-apoptotic and autophagic pathways.

PMID- 29032012
TI  - Continuous subcutaneous apomorphine infusion in Parkinson's disease patients with
      cognitive dysfunction: A retrospective long-term follow-up study.
AB  - INTRODUCTION: Continuous apomorphine infusion (CAI) is an advanced therapy in
      fluctuating Parkinson's disease (PD). The use of CAI is controversial in PD
      patients with cognitive dysfunction including visual hallucinations (VHs), and
      orthostatic hypotension (OH). This study was set-up to analyze the effectiveness
      and safety of CAI in elderly PD patients with cognitive dysfunction. METHODS:
      This new-user cohort study identified fluctuating PD patients who started CAI
      treatment at the rehabilitation unit of Parkinson Expertise Center (RU-PEC)
      Groningen, from November 2004 until 2016. Efficacy and safety data included motor
      function, cognitive status, OH and VHs, and was analyzed retrospectively. Pre
      existent non-motor symptoms were treated optimally before starting CAI. RESULTS:
      Forty-five fluctuating PD patients (age: 70.9 +/- 8.1 yrs, disease duration: 10.8
      +/- 4.8 yrs) were identified, with pre-existing cognitive dysfunction, VHs (71%),
      and OH (26%). During the stay at RU-PEC (median 52 days) apomorphine was
      successfully titrated without worsening of pre-existing VHs and OH. The mean
      daily apomorphine dose was 66 +/- 28 mg, accompanied by a reduction of levodopa
      equivalent daily dose (LEDD) with 17%. The duration of ON-time and OFF-time
      significantly improved with +2.36 h (25%) and -1.66 h (-45%), respectively, while
      dyskinesia duration did not change. During long-term follow-up (median of 26
      months) VHs and OH worsened in 9 and 4 patients, which necessitated
      discontinuation in 4 cases. CONCLUSION: This study demonstrates that CAI is also
      an effective treatment in advanced PD patients with concomitant cognitive
      dysfunction including VHs and OH, provided that these comorbidities are treated
      adequately as well.

PMID- 29032013
TI  - The presence of depression and anxiety do not distinguish between functional
      jerks and cortical myoclonus.
AB  - INTRODUCTION: Functional movement disorders are accompanied by a high occurrence
      of psychopathology and cause serious impairments in quality of life. However,
      little is known about this in patients with functional jerks and no comparison
      has been made between patients with functional jerks and organic myoclonus. This
      case control study compares the occurrence of depression, anxiety and quality of
      life (HR-QoL) in patients with functional jerks and cortical myoclonus. METHODS:
      Patients with functional jerks and cortical myoclonus, consecutively recruited,
      were compared on self-rated anxiety (Beck Anxiety Inventory), depression (Beck
      Depression Inventory), health-related quality of life (RAND-36), and myoclonus
      severity (UMRS and CGI-S rating scales). RESULTS: Sixteen patients with
      functional jerks and 23 with cortical myoclonus were evaluated. There was no
      significant difference in depression (44% vs. 43%) or anxiety (44% vs. 47%)
      scores between groups. The HR-QoL was similarly impaired except that functional
      jerks patients reported significantly more pain (p < 0.05). Only in the
      functional jerks group myoclonus severity correlated with depression and anxiety.
      CONCLUSION: Depression and anxiety scores are high and do not discriminate
      between functional jerks and cortical myoclonus. Quality of life was equally
      impaired in both sub-groups, but pain was significantly worse in patients with
      functional jerks.

PMID- 29032014
TI  - High-intermediate prostate cancer treated with low-dose-rate brachytherapy with
      or without androgen deprivation therapy.
AB  - PURPOSE: To describe outcomes of men with unfavorable (high-tier) intermediate
      risk prostate cancer (H-IR) treated with low-dose-rate (LDR) brachytherapy, with
      or without 6 months of androgen deprivation therapy (ADT). METHODS AND MATERIALS:
      Patients with H-IR prostate cancer, treated before 2012 with LDR brachytherapy
      without external radiation are included. Baseline tumor characteristics are
      described. Outcomes between groups receiving ADT are measured by Phoenix (nadir
      +2 ng/mL), and threshold 0.4 ng/mL biochemical relapse definitions (bNEDs), as
      well as clinical end points. Standard descriptive and actuarial statistics are
      used. RESULTS: Two hundred sixty men were eligible, 139 (53%) did not receive ADT
      and 121 (47%) did. Median follow-up was 5 years. Men treated with ADT had higher
      T stage and percent positive cores but lower pathologic grade group. bNED rates
      with and without ADT at 5 years are 86% and 85% (p = 0.52) with the Phoenix
      definition, and 83% and 78% (p = 0.13) with the threshold definition. Local
      recurrence or metastasis were rare in both groups (<5%, p = not significant).
      Death from prostate cancer only occurred in 4 patients, 2 in each group. Overall
      survival was 85% in those treated with ADT and 93% without at 8 years, p = 0.15.
      CONCLUSIONS: The addition of 6 months of ADT to LDR brachytherapy for H-IR
      prostate cancer does not improve 5 year prostate specific antigen control, and we
      no longer routinely recommended it.

PMID- 29032015
TI  - Possible positive effect of the APOE epsilon2 allele on cognition in early to mid
      adult life.
AB  - BACKGROUND: epsilon4 allele possession is associated with an increased risk of
      Alzheimer's disease. Its effects earlier in life are less well understood.
      Previous studies have reported both detrimental effects and a lack of effect on
      cognition outside dementia. We used genotype based recall from the ALSPAC study
      to investigate whether APOE genotype influences cognition in earlier adult life.
      METHODS: We invited all individuals with the rarer epsilon22 or epsilon44
      genotypes and equal numbers of those with epsilon32, epsilon33 or epsilon34 APOE
      genotypes (total n invited = 1936, ages 23-67). Participants were screened for
      dementia using the Addenbrooke's Cognitive Examination Revised (ACE-R).
      Participants were asked to complete a 3 h battery of neuropsychological tests
      covering a range of cognitive domains. The primary outcome was performance on the
      Rey Auditory Verbal Learning Test (RAVLT). Transformation of variables was used
      where required to permit parametric testing. As genotypes are unlikely to be
      confounded unadjusted analyses were performed. RESULTS: 114 participants were
      recruited to the study (39 epsilon33, 27 epsilon34, 15 epsilon44, 26 epsilon32 &
      7 epsilon22). epsilon4+ participants had higher scores on the cognitive failures
      questionnaire (10 point increase, p = 0.006) but no deficits on objective
      cognitive testing. epsilon2 carriers had slightly better episodic memory
      performance (p = 0.016), slightly improved n-back accuracy and better executive
      functioning (trails A&B, p = 0.005). CONCLUSIONS: It is intriguing that the
      epsilon2+ group performed better as this group have a lower risk of Alzheimer's
      disease. Most previous studies have analysed as epsilon4/non epsilon4 so may have
      missed this effect.

PMID- 29032016
TI  - Neuropsychological outcomes following paediatric temporal lobe surgery for
      epilepsies: Evidence from a systematic review.
AB  - OBJECTIVE: The systematic review aimed to assess the neuropsychological outcomes
      of temporal lobe resections for epilepsy in children. Additional objectives
      included determining whether earlier age at surgery leads to better
      neuropsychological outcomes; the relationships between and predictors of these
      outcomes. METHODS: Using advanced search terms, a systematic review of electronic
      databases was conducted, comprising MEDLINE, Embase, PsycINFO, Global Health, Web
      of Science and CINAHL. Included studies reported on outcome following
      neurosurgical treatment for epilepsy. Specifically, studies were included if they
      reported neuropsychological outcomes and were concerned only with temporal lobe
      resection. RESULTS: 73 studies met inclusion criteria. For reported
      neuropsychological outcomes, the majority of participants remained stable after
      surgery; some declined and some improved. There was some evidence for increased
      material-specific memory deficits after temporal lobe surgery based on resection
      side, and more positive cognitive outcome for those with lower pre-surgical
      ability level. SIGNIFICANCE: Retrieved evidence highlights the need for
      improvements to quality of methodology and reporting. Appropriately designed
      prospective multicentre trials should be conducted with adequate follow-up for
      long-term outcomes to be measured. Core outcome measures should be agreed between
      centres. This would permit higher quality evidence so that clinicians, young
      people and their families may make better informed decisions about whether or not
      to proceed with surgery and likely post-operative profile.

PMID- 29032017
TI  - Next-generation sequencing technology a new tool for killer cell immunoglobulin
      like receptor allele typing in hematopoietic stem cell transplantation.
AB  - Killer cell Immunoglobulin-like Receptor (KIR) genes are a family of genes
      located together within the leukocyte receptor cluster on human chromosome
      19q13.4. To date, 17 KIR genes have been identified including nine inhibitory
      genes (2DL1/L2/L3/L4/L5A/L5B, 3DL1/L2/L3), six activating genes
      (2DS1/S2/S3/S4/S5, 3DS1) and two pseudogenes (2DP1, 3DP1) classified into group A
      (KIR A) and group B (KIR B) haplotypes. The number and the nature of KIR genes
      vary between the individuals. In addition, these KIR genes are known to be
      polymorphic at allelic level (907 alleles described in July 2017). KIR genes
      encode for receptors which are predominantly expressed by Natural Killer (NK)
      cells. KIR receptors recognize HLA class I molecules and are able to kill
      residual recipient leukemia cells, and thus reduce the likelihood of relapse. KIR
      alleles of Hematopoietic Stem Cell (HSC) donor would require to be known (Alicata
      et al. Eur J Immunol 2016) because the KIR allele polymorphism may affect both
      the KIR+ NK cell phenotype and function (Gagne et al. Eur J Immunol 2013; Bari R,
      et al. Sci Rep 2016) as well as HSCT outcome (Boudreau et al. JCO 2017). The
      introduction of the Next Generation Sequencing (NGS) has overcome current
      conventional DNA sequencing method limitations, known to be time consuming.
      Recently, a novel NGS KIR allele typing approach of all KIR genes was developed
      by our team in Nantes from 30 reference DNAs (Maniangou et al. Front in Immunol
      2017). This NGS KIR allele typing approach is simple, fast, reliable, specific
      and showed a concordance rate of 95% for centromeric and telomeric KIR genes in
      comparison with high-resolution KIR typing obtained to those published data using
      exome capture (Norman PJ et al. Am J Hum Genet 2016). This NGS KIR allele typing
      approach may also be used in reproduction and to better study KIR+ NK cell
      implication in the control of viral infections.

PMID- 29032018
TI  - 100% voluntary blood donation in India by 2020: A difficult goal to fathom.

PMID- 29032019
TI  - [Experience with infections in the use of extracorporeal membrane oxygenation].
AB  - OBJECTIVE: To identify risk factors associated with infectious complications
      acquired by paediatric patients during extracorporeal life support (ECLS).
      PATIENTS AND METHODS: Patients under ECLS from January 2011 to December 2014 have
      been retrospectively reviewed and data on demographics, care and infectious
      complications were collected. RESULTS: There were 50 ECLS assistances in the
      study period, of which 20 patients had 23 infectious complications: 16 were
      bloodstream infections, with coagulase negative staphylococci being the
      predominant isolate (there were 2 cases of candidaemia). Age, site of cannulation
      procedure, cannulation site, severe coagulopathy, and surgical interventions
      during assistance were analysed as risk factors for infectious complications, but
      no significant differences were found. ECLS duration was significantly longer in
      patients with infectious complications (8.91 vs 5.91 days; P=.039). There were no
      significant differences as regards Paediatric Intensive Care Unit (PICU) stay, or
      in survival. CONCLUSIONS: Infectious complications during ECLS are very common,
      and ECLS duration is significantly longer in patients with infections. Measures
      should be put in place to prevent infectious complications and reduce time on
      ECLS.

PMID- 29032020
TI  - Long-term impact of suboptimal rotavirus vaccines on acute gastroenteritis in
      hospitalized children in Northern Taiwan.
AB  - BACKGROUND/PURPOSE: Rotavirus vaccines were launched in Taiwan since early 2006.
      Our study was aimed to figure out long-term extended molecular epidemiology in
      acute gastroenteritis (AGE) in hospitalized young children after rotavirus
      vaccination in Taiwan. METHODS: During the 10-year period from January 2007 to
      December 2016, fecal samples from children under 5 years old with AGE
      hospitalized in Chang Gung Children's Hospital (CGCH) were examined for enteric
      pathogens and they were divided into two time intervals: early post-vaccine (Jan.
      2007 to Dec. 2011; EPV) and late post-vaccine (Jan. 2012 to Dec. 2016; LPV).
      RESULTS: In total, 837 patients with AGE were enrolled with complete study. In
      the EPV period, 106 (26.7%) rotavirus and 65 (16.4%) norovirus infections were
      identified as major pathogens. In the LPV period, 79 (17.9%) rotavirus and 98
      (22.2%) norovirus infections were diagnosed. Statistical analyses showed a
      significantly decreased prevalence of rotavirus infection (P = 0.002) and a
      significantly increased prevalence of norovirus (P = 0.034) and enteric bacterial
      infections (P < 0.001). A substantial decrease of rotavirus G1 (P = 0.079) in the
      LPV period and norovirus GII.4 prevailed through the decade. CONCLUSION: In
      Taiwan, under a suboptimal rotavirus vaccination policy, there was a marked
      decrease in the rate of rotavirus AGE of hospitalized young children.
      Significantly increased norovirus infection has replaced rotavirus as the leading
      cause. Expansion of rotavirus vaccine coverage, development of a norovirus
      prevention strategy, and sustained bacterial infection control are important for
      AGE containment in children in Taiwan.

PMID- 29032021
TI  - Clinical characteristics and survival outcomes of terminally ill patients
      undergoing withdrawal of mechanical ventilation.
AB  - BACKGROUND: Withdrawal of mechanical ventilation is an important, but rarely
      explored issue in Asia during end-of-life care. This study aimed to describe the
      clinical characteristics and survival outcomes of terminally ill patients
      undergoing withdrawal of mechanical ventilation in Taiwan. METHODS: One-hundred
      thirty-five terminally ill patients who had mechanical ventilation withdrawn
      between 2013 and 2016, from a medical center in Taiwan, were enrolled. Patients'
      clinical characteristics and survival outcomes after withdrawal of mechanical
      ventilation were analyzed. RESULTS: The three most common diagnoses were organic
      brain lesion, advanced cancer, and newborn sequelae. The initiator of the
      withdrawal process was family, medical personnel, and patient him/herself. The
      median survival time was 45 min (95% confidence interval, 33-57 min) after the
      withdrawal of mechanical ventilation, and 102 patients (75.6%) died within one
      day after extubation. The median time from diagnosis of disease to receiving life
      sustaining treatment and artificial ventilation support, receiving life
      sustaining treatment and artificial ventilation support to "Withdrawal meeting,"
      "Withdrawal meeting" to ventilator withdrawn, and ventilator withdrawn to death
      was 12.1 months, 19 days, 1 day, and 0 days, respectively. Patients with a
      diagnosis of advanced cancer and withdrawal initiation by the patients themselves
      had a significantly shorter time interval between receiving life-sustaining
      treatment and artificial ventilation support to "Withdrawal meeting" compared to
      those with non-cancer diseases and withdrawal initiation by family or medical
      personnel. CONCLUSION: This study is the first observational study to describe
      the patients' characteristics and elaborate on the survival outcome of withdrawal
      of mechanical ventilation in patients who are terminally ill in an Asian
      population. Understanding the clinical characteristics and survival outcomes of
      mechanical ventilation withdrawal might help medical personnel provide
      appropriate end-of-life care and help patients/families decide about the
      withdrawal process earlier.

PMID- 29032022
TI  - Outcomes of Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia Following an
      Elective Switch From Second-Generation Tyrosine Kinase Inhibitor to Imatinib.
AB  - The second-generation tyrosine kinase inhibitors (TKIs) (2G-TKIs) dasatinib (DAS)
      and nilotinib (NIL) yield faster responses in newly diagnosed chronic phase (CP)
      chronic myeloid leukemia (CML) as compared with imatinib (IM); however, long-term
      safety of these agents is a growing concern. We identified 20 patients with CP
      CML diagnosed between August 2013 and October 2016 who initiated 2G-TKIs and were
      then switched after optimal response at 3 months to IM. Second-generation TKIs
      initiated were DAS (n = 15), NIL (n = 3), or both sequentially due to intolerance
      (n = 1). One other patient initiated therapy with ponatinib on trial. Response
      was assessed by quantitative reverse-transcriptase polymerase chain reaction (qRT
      PCR) for BCR-ABL1 levels every 3 months and in patients with qRT-PCR values less
      than 10% at 3 months, IM was started at 400 mg/d. IM was well tolerated except in
      2 patients who required dose-reduction and discontinuation due to grade 2 skin
      rash (1) and grade 2 anxiety (1). After initiation of IM therapy, the BCR-ABL1
      qRT-PCR levels trended down as expected. At 12 months 16 (84.2%) of 19 evaluable
      patients showed a 3 log (major molecular remission) or better reduction in their
      PCR levels. In conclusion, this retrospective analysis shows that IM can be
      safely and effectively administered following optimal response to 2G-TKIs. A
      prospective trial exploring this approach is currently enrolling and will be
      needed to confirm the safety and efficacy of this therapeutic approach.

PMID- 29032023
TI  - Social determinants of drug-related mortality in a general population.
AB  - BACKGROUND: We investigated the association between social determinants and a
      broad selection of drug-related deaths in a general population. METHODS: We
      conducted a follow-up of an 11% random sample of working-age Finnish residents
      for 1996-2007 linked with an oversampling of deaths and population registration
      data on social characteristics. We defined total drug-related deaths as those
      from psychoactive substance use disorders and drug-induced poisonings (drug
      induced deaths) as well as drug-related accidents, homicides, illnesses, and
      suicides. RESULTS: The number of drug-related deaths was three times that of drug
      induced deaths. We found the highest hazard ratios (HRs) for total drug-related
      mortality for long-term unemployment (4.9; 95% confidence interval [CI], 4.3
      5.6), short-term unemployment (3.9; 95% CI, 3.5-4.4), and retirement (5.8; 95%
      CI, 5.1-6.8). The HRs were highest for mortality related to psychoactive
      substance use disorders and lowest for mortality related to drug-related
      suicides. The differences were large for both sexes. CONCLUSIONS: Drug-related
      mortality was associated with social disadvantage; however, the strength of the
      association varied by drug-related cause of death. Primary and secondary
      prevention of drug use should particularly target disadvantaged groups.

PMID- 29032024
TI  - Characteristics of self-inflicted drug overdose deaths in North Carolina.
AB  - BACKGROUND: Drug overdose mortality is a major public health concern in the
      United States, with prescription opioids contributing substantially to recent
      increases in drug overdose deaths. Compared to unintentional drug overdose
      deaths, relatively little data describes intentional self-inflicted drug overdose
      deaths (i.e., suicide by drug overdose). The aim of this study was to examine the
      characteristics of self-inflicted drug overdose deaths, overall and in comparison
      to unintentional drug overdose deaths. METHODS: We linked vital statistics,
      prescription drug monitoring program, and toxicology data for self-inflicted and
      unintentional drug overdose deaths among North Carolina residents in 2012.
      RESULTS: Most self-inflicted (79.2%) and unintentional (75.6%) drug overdose
      decedents had a prescription for a controlled substance within one year of death.
      Toxicology results revealed that antidepressants contributed to a significantly
      higher percent of self-inflicted compared to unintentional drug overdose deaths
      (45.0% vs. 8.1%). Among deaths in which commonly prescribed opioids (oxycodone,
      hydrocodone) or benzodiazepines (alprazolam, clonazepam) contributed to death, a
      significantly higher percent of self-inflicted drug overdose decedents had a
      prescription for the substance within 30days of death compared to unintentional
      drug overdose decedents. CONCLUSIONS: The results highlight the use of
      prescription opioids, benzodiazepines, and antidepressants among self-inflicted
      drug overdose decedents. Importantly, the results indicate that self-inflicted
      drug overdose decedents were more likely than unintentional drug overdose
      decedents to have potential contact with the health care system in the weeks
      preceding death, offering an opportunity for professionals to identify and
      intervene on risk factors or signs of distress and potential for self-harm.

PMID- 29032025
TI  - Characteristics of drinking events associated with heavy episodic drinking among
      adolescents in the United States.
AB  - PURPOSE: To examine associations between characteristics of drinking events and
      the quantity of alcohol consumed by adolescents in the United States. METHODS:
      Analyses relied on 2011-2015 data from the National Survey on Drug Use and Health
      (NSDUH). The study sample included 8110 adolescents, ages 12-17years old, who
      drank alcohol in the past 30days. A logistic regression model, weighted for
      national estimation, was constructed to examine factors associated with heavy
      episodic drinking (HED; 5+ drinks for males, 4+ drinks for females) during the
      underage drinker's most recent drinking event. These models were adjusted for
      study year and individual characteristics, including past year drinking
      frequency, age of drinking onset, and demographic variables. RESULTS: Buying
      alcohol off-premise or from another person and being given alcohol from non
      parent social sources were associated with greater odds of HED compared to being
      given alcohol by one of their parents. Drinking alcohol at someone else's house
      or multiple locations were associated with heavier alcohol consumption compared
      to drinking at one's own home. Being older and an earlier age of alcohol onset
      were associated with greater odds of HED. CONCLUSIONS: This study identifies
      contextual factors associated with HED by adolescents. Compared to global
      association studies, the findings from these event-specific analyses provide
      strong evidence of the environmental conditions that contribute to HED in
      American adolescents. Although no level of alcohol consumption is safe for
      adolescents, knowledge of event-level risk factors can inform targeted
      interventions.

PMID- 29032026
TI  - 4-Hydroxy-2-pyridones: Discovery and evaluation of a novel class of antibacterial
      agents targeting DNA synthesis.
AB  - The continued emergence of bacteria resistant to current standard of care
      antibiotics presents a rapidly growing threat to public health. New chemical
      entities (NCEs) to treat these serious infections are desperately needed. Herein
      we report the discovery, synthesis, SAR and in vivo efficacy of a novel series of
      4-hydroxy-2-pyridones exhibiting activity against Gram-negative pathogens.
      Compound 1c, derived from the N-debenzylation of 1b, preferentially inhibits
      bacterial DNA synthesis as determined by standard macromolecular synthesis
      assays. The structural features of the 4-hydroxy-2-pyridone scaffold required for
      antibacterial activity were explored and compound 6q, identified through further
      optimization of the series, had an MIC90 value of 8 MUg/mL against a panel of
      highly resistant strains of E. coli. In a murine septicemia model, compound 6q
      exhibited a PD50 of 8 mg/kg in mice infected with a lethal dose of E. coli. This
      novel series of 4-hydroxy-2-pyridones serves as an excellent starting point for
      the identification of NCEs treating Gram-negative infections.

PMID- 29032028
TI  - Comments on "Radiological protection for pregnant women at a large academic
      medical Cancer Center".

PMID- 29032029
TI  - CXCR5+CD8+ T cells could induce the death of tumor cells in HBV-related
      hepatocellular carcinoma.
AB  - The follicular CXCR5+CD8+ T cells have recently emerged as a critical cell type
      in mediating peripheral tolerance as well as antiviral immune responses during
      chronic infections. In this study, we investigated the function of CXCR5+CD8+ T
      cells in HBV-related hepatocellular carcinoma patients. Compared to CXCR5-CD8+ T
      cells, CXCR5+CD8+ T cells presented elevated PD-1 expression but reduced Tim-3
      and CTLA-4 expression. Upon anti-CD3/CD28 stimulation, CXCR5+CD8+ T cells
      demonstrated higher proliferation potency than CXCR5-CD8+ T cells, especially
      after PD-1 blockade. CXCR5+CD8+ T cells also demonstrated significantly higher
      granzyme B synthesis and release, as well as higher level of degranulation. Tumor
      cells were more readily eliminated by CXCR5+CD8+ T cells than by CXCR5-CD8+ T
      cells. Interestingly, we found that B cells were more resistant to CXCR5+CD8+ T
      cell-mediated killing than tumor cells, possibly through IL-10-mediated
      protection. In addition, the CXCR5+CD8+ T cell-mediated cytotoxic effects on
      tumor cells could be significantly enhanced by PD-L1 blockade. Together, we
      presented that in patients with in HBV-related hepatocellular carcinoma,
      CXCR5+CD8+ T cells could mediate tumor cell death more potently than the CXCR5
      CD8+ T cells in vitro while the autologous B cells were protected.

PMID- 29032027
TI  - Peripheral Neuropathy and Hindlimb Paralysis in a Mouse Model of Adipocyte
      Specific Knockout of Lkb1.
AB  - Brown adipose tissues (BAT) burn lipids to generate heat through uncoupled
      respiration, thus representing a powerful target to counteract lipid accumulation
      and obesity. The tumor suppressor liver kinase b1 (Lkb1) is a key regulator of
      cellular energy metabolism; and adipocyte-specific knockout of Lkb1 (Ad-Lkb1 KO)
      leads to the expansion of BAT, improvements in systemic metabolism and resistance
      to obesity in young mice. Here we report the unexpected finding that the Ad-Lkb1
      KO mice develop hindlimb paralysis at mid-age. Gene expression analyses indicate
      that Lkb1 KO upregulates the expression of inflammatory cytokines in
      interscapular BAT and epineurial brown adipocytes surrounding the sciatic nerve.
      This is followed by peripheral neuropathy characterized by infiltration of
      macrophages into the sciatic nerve, axon degeneration, reduced nerve conductance,
      and hindlimb paralysis. Mechanistically, Lkb1 KO reduces AMPK phosphorylation and
      amplifies mammalian target-of-rapamycin (mTOR)-dependent inflammatory signaling
      specifically in BAT but not WAT. Importantly, pharmacological or genetic
      inhibition of mTOR ameliorates inflammation and prevents paralysis. These results
      demonstrate that BAT inflammation is linked to peripheral neuropathy.

PMID- 29032030
TI  - Design, synthesis and biological evaluation of N-(4-alkoxy-3
      cyanophenyl)isonicotinamide/nicotinamide derivatives as novel xanthine oxidase
      inhibitors.
AB  - A series of N-(4-alkoxy-3-cyanophenyl)isonicotinamide/nicotinamide derivatives
      was designed, synthesized and evaluated for inhibitory potency in vitro against
      xanthine oxidase. The isonicotinamide series was considerably more effective than
      the nicotinamide series. SARs analysis revealed that the isonicotinoyl moiety
      played a significant role on the inhibition and that a benzyl ether tail (e.g.,
      ortho-cyanobenzoxy) linked to the benzonitrile moiety benefits the inhibitory
      potency. Among these compounds, 10q (IC50 = 0.3 MUM) was identified to be the
      most potent in this work and was observed to be 28.3-fold more potent than
      allopurinol but 20-fold less potent than topiroxostat. The Lineweaver-Burk plot
      showed that 10q acted as a mixed-type inhibitor on xanthine oxidase. Molecular
      modeling provided a reasonable explanation for the SARs observed in this study.

PMID- 29032031
TI  - Discovery of novel anti-angiogenesis agents. Part 8: Diaryl thiourea bearing 1H
      indazole-3-amine as multi-target RTKs inhibitors.
AB  - VEGFR-2, TIE-2, and EphB4 are essential for both angiogenesis and tumorigenesis.
      Herein, we designed and prepared three classes of multi-target inhibitors based
      on the extensive sequence homology along the kinase domain of angiogenic RTKs.
      Biological evaluation indicated that these multi-target inhibitors exhibited
      considerable potential as novel anti-angiogeneic and anticancer agents. Among
      them, a diaryl thiourea bearing 1H-indazole-3-amine (16a) displayed the most
      potent RTK inhibition and excellent selectivity. It also showed inhibition on
      viability of human umbilical vein endothelial cells and anti-proliferation
      against a broad spectrum of cancer cells. Therefore, 1H-indazole-3-amine could
      serve as a promising hinge binding group for multi-target inhibitors of VEGFR-2,
      Tie-2, and EphB4.

PMID- 29032032
TI  - Enzyme inhibitory activities an insight into the structure-Activity relationship
      of biscoumarin derivatives.
AB  - Biscoumarin derivatives, a dimeric form of coumarin, are well known derivatives
      of coumarin, occurred in the bioactive metabolites of marine and terrestrial
      organisms. On account of pharmacological and biological applications,
      biscoumarins have long been the subject of innumerable enzyme inhibition studies.
      In this review the pros and cons of enzyme inhibition studies of biscoumarins as
      urease inhibitors, aromatase inhibitors, NPPs, alpha-glucosidase inhibitors,
      alpha-amylase inhibitors, HIV-1 integrase inhibition, steroid sulfatase
      inhibitors and c-Met inhibitors are discussed in a systematic way. Moreover, the
      review discusses the structure activity relationship of biscoumarin scaffold with
      enzyme inhibitory potency which would unleash new avenues for further
      development. The purpose of the current review is to disclose the value of
      biscoumarins as potent and efficient enzyme inhibitor. This review provides a
      guideline to elaborate the diversity of biscoumarin inhibitors by exploring the
      effects of electronic groups linked with biscoumarin nucleus.

PMID- 29032033
TI  - Effect of mofezolac-galactose distance in conjugates targeting cyclooxygenase
      (COX)-1 and CNS GLUT-1 carrier.
AB  - Neuroinflammation is the earliest stage of several neurological and
      neurodegenerative diseases. In the case of neurodegenerative disorders, it takes
      place about 15-20 years before the appearance of specific neurodegenerative
      clinical symptoms. Constitutive microglial COX-1 is one of the pro-inflammatory
      players of the neuroinflammation. Novel compounds 3, 14 and 15 (Galmof0, Galmof5
      and Galmof11, respectively) were projected, and their synthetic methodologies
      developed, by linking by an ester bond, directly or through a C5 or C11 unit
      linker the highly selective COX-1 inhibitor mofezolac (COXs selectivity index >
      6000) to galactose in order to obtain substances capable to cross blood-brain
      barrier (BBB) and control the CNS inflammatory response. 3, 14 and 15 (Galmofs)
      were prepared in good to fair yields. Galmof0 (3) was found to be a selective COX
      1 inhibitor (COX-1 IC50 = 0.27 MUM and COX-2 IC50 = 3.1 MUM, selectivity index =
      11.5), chemically and metabolically stable, and capable to cross Caco-2 cell
      monolayer, resembling BBB, probing that its transport is GLUT-1-mediated.
      Furthermore, Galmof0 (3) powerfully inhibits PGE2 release higher than mofezolac
      (1) in LPS-stimulated mouse BV2 microglial cell line, a worldwide recognized
      neuroinflammation model. In addition, Fingerprints for Ligands and Proteins
      (FLAP) was used to explain the different binding interactions of Galmofs with the
      COX-1 active site.

PMID- 29032034
TI  - Therapeutic investigations of novel indoxyl-based indolines: A drug target
      validation and Structure-Activity Relationship of angiotensin-converting enzyme
      inhibitors with cardiovascular regulation and thrombolytic potential.
AB  - A family of 12 members of Naphthalene-2-ol-indolin-2-one-thiocarbamides (5a-l)
      with pharmacological potentials of cardiovascular modulator were efficiently
      synthesized and evaluated. These compounds show inhibitory activity on
      angiotensin-converting enzyme (ACE), which is a principal constituent of the
      renin-angiotensin system and causative source for hypertension (HTN) (elevated
      blood pressure) and congestive heart failure (CHF), a parameter that was tested
      in this report. Prior to this, to get more insight into the binding mode and
      inhibition of human ACE C-domain (PDB ID: 2XY9) and N-domain (PDB ID: 3NXQ)
      compounds 5a-l was docked into the active site of them. The established
      inhibitory constant (Ki) (range 40-500 nM) and least binding affinities (-18.52
      to -30.57 kcal/mol) indicated the therapeutic selectivity of compounds 5a-l
      towards ACE C-domain inhibition over ACE N-domain. The cytotoxicity effect of
      most potent compounds among 5a-l were tested in normal breast cells and MCF-7
      cell lines. Simultaneously, H2O2 induced antioxidant and DNA damage assessment
      was executed. Eventually, a thrombolytic activity followed by a human red blood
      cell (HRBC) membrane stabilization study to ensure the relaxation of blood and
      stabilization of RBC was executed. Structure-Activity Relationship (SAR) study
      discloses the potential of 5c, 5h, and 5k as cardiovascular protective
      therapeutic agents among 5a-l.

PMID- 29032035
TI  - Small RNAs: Big Impact on Plant Development.
AB  - While the role of proteins in determining cell identity has been extensively
      studied, the contribution of small noncoding RNA molecules such as miRNAs and
      siRNAs has been also recognised. miRNAs bind to complementary sites in target
      mRNA molecules to trigger the degradation or translational inhibition of those
      targets. Recent studies have revealed that miRNAs play pivotal roles in key
      developmental processes such as patterning of the embryo, meristem, leaf, and
      flower. Furthermore, these miRNAs have been recruited throughout plant evolution
      into pathways that create diverse plant organ forms and shapes. This review
      focuses on the roles of miRNAs in establishing plant cell identity during key
      plant development processes and creating morphological diversity during plant
      evolution.

PMID- 29032036
TI  - Relationship Between the Subcostal and Right Lateral Ultrasound Views of Inferior
      Vena Cava Collapse: Implications for Clinical Use of Ultrasonography.
AB  - BACKGROUND: The collapsibility index of the inferior vena cava is traditionally
      visualized from the subcostal region in the sagittal plane, referred to here as
      cIVCSS. Alternatively, the collapsibility index of the inferior vena cava can be
      visualized from the right midaxillary line in the coronal plane, referred to here
      as cIVCRC. It is unclear whether values of cIVCRC are comparable with values of
      cIVCSS because the inferior vena cava collapses asymmetrically into an elliptical
      form, quantified as the flat ratio of the inferior vena cava (F-IVC). This study
      aimed (1) to establish if cIVCRC is concordant or discordant to cIVCSS, and (2)
      to describe how this concordance or discordance is related to F-IVC. METHODS:
      This single-center cross-sectional study enrolled 110 spontaneously breathing
      patients. Values of cIVCRC were compared with cIVCSS. Performance of cIVCRC >=
      42% in predicting fluid responsiveness, defined as cIVCSS >= 42%, was assessed. F
      IVC was also correlated to the difference between cIVCSS and cIVCRC. RESULTS:
      cIVCRC >= 42% was 61.5% sensitive (95% CI, 31.58%-86.14%) and 67.1% specific (95%
      CI, 55.81%-77.06%) for predicting cIVCSS >= 42%. cIVCRC underestimated cIVCSS.
      The degree of discordance between cIVCRC and cIVCSS was proportional to the value
      of F-IVC. CONCLUSIONS: cIVCRC and cIVCSS measures are discordant, where cIVCRC
      underestimates cIVCSS. The degree of discordance is directly proportional to the
      value of F-IVC. Therefore, we recommend that cIVCRC >= 42% be used to rule in,
      but not to rule out, fluid responsivity. Wherever possible, F-IVC should be
      assessed to understand the clinical relevance of cIVCRC.

PMID- 29032037
TI  - Ecocultural range-expansion scenarios for the replacement or assimilation of
      Neanderthals by modern humans.
AB  - Recent archaeological records no longer support a simple dichotomous
      characterization of the cultures/behaviors of Neanderthals and modern humans, but
      indicate much cultural/behavioral variability over time and space. Thus, in
      modeling the replacement or assimilation of Neanderthals by modern humans, it is
      of interest to consider cultural dynamics and their relation to demographic
      change. The ecocultural framework for the competition between hominid species
      allows their carrying capacities to depend on some measure of the levels of
      culture they possess. In the present study both population densities and the
      densities of skilled individuals in Neanderthals and modern humans are spatially
      distributed and subject to change by spatial diffusion, ecological competition,
      and cultural transmission within each species. We analyze the resulting range
      expansions in terms of the demographic, ecological and cultural parameters that
      determine how the carrying capacities relate to the local densities of skilled
      individuals in each species. Of special interest is the case of cognitive and
      intrinsic-demographic equivalence of the two species. The range expansion
      dynamics may consist of multiple wave fronts of different speeds, each of which
      originates from a traveling wave solution. Properties of these traveling wave
      solutions are mathematically derived. Depending on the parameters, these
      traveling waves can result in replacement of Neanderthals by modern humans, or
      assimilation of the former by the latter. In both the replacement and
      assimilation scenarios, the first wave of intrusive modern humans is
      characterized by a low population density and a low density of skilled
      individuals, with implications for archaeological visibility. The first invasion
      is due to weak interspecific competition. A second wave of invasion may be
      induced by cultural differences between moderns and Neanderthals. Spatially and
      temporally extended coexistence of the two species, which would have facilitated
      the transfer of genes from Neanderthal into modern humans and vice versa, is
      observed in the traveling waves, except when niche overlap between the two
      species is extremely high. Archaeological findings on the spatial and temporal
      distributions of the Initial Upper Palaeolithic and the Early Upper Palaeolithic
      and of the coexistence of Neanderthals and modern humans are discussed.

PMID- 29032038
TI  - A role of cathepsin L gene in innate immune response of crayfish (Procambarus
      clarkii).
AB  - Cathepsin L is one of the crucial enzyme superfamilies and involved in the immune
      responses. In the present study, cathepsin L gene from the red crayfish
      Procambarus clarkii, named PcCTSL, was cloned and characterized. The cDNA
      fragment of PcCTSL was 1026 bp in length, which encoded a putative protein of 341
      amino acid residues with a molecular weight of 37.884 kDa. The theoretical
      isoelectric point was 5.218. The prepro-cathepsin L was comprised of a typical
      signal peptide (Met1-Ala18), a prodomain proregion peptide (Trp29-Phe89) and a
      mature peptide (Leu124-Leu340). Homology analysis indicated that PcCTSL exhibited
      53.2%-87.1% identity to other selected species. The recombinant protein of PcCTSL
      was successfully expressed in Escherichia coli and rabbit anti-PcCTSL polyclonal
      antibodies were prepared. Real-time quantitative reverse transcription-PCR (qPCR)
      analysis revealed that the PcCTSL was expressed in all examined tissues, while
      the greatest mRNA level was observed in hepatopancreas. The expression of PcCTSL
      mRNA was clearly up regulated in hepatopancreas after challenge by
      lipopolysaccharide (LPS) and polyriboinosinic polyribocytidylic acid (Poly I:C).
      RNA interference of PcCTSL affected the gene expression of members of the Toll
      pathway. Our results suggest that the PcCTSL may play an important role to defend
      P. clarkii against the pathogens infection.

PMID- 29032039
TI  - The efficacy of Poly-beta-Hydroxy Butyrate (PHB)/biosurfactant derived from
      Staphylococcus hominis against White Spot Syndrome Virus (WSSV) in Penaeus
      monodon.
AB  - White Spot Syndrome Virus (WSSV) is one of the most important causative agents of
      Penaeid shrimps diseases that incur heavy losses to the shrimp aquaculture. It
      has severe impact on the sustainability and the production of Penaeus monodon.
      Hence, the present study focussed on the investigation of Poly-beta
      hydroxybutyrate/biosurfactant as immunostimulants against WSSV infected shrimps.
      Infection of WSSV was periodically checked in all the experimental shrimps using
      PCR diagnostic kit. After ensuring all shrimps were free of viral infection,
      experiments were carried out to analyze the nonspecific immune responses
      (prophenol oxidase, nitro blue tetrazolium reduction assay and total haemocyte
      count) both in control and experimental group. Further, gills and muscles of
      Penaeus monodon were subjected to proteome analysis after treated it with
      PHB/biosurfactant independently in the concentration of 2% and 5% each. Increase
      in the level of haemocytes was observed in both PHB (26 +/- 2 * 104
      cells)/biosurfactant (28 +/- 2 * 104 cells) treated shrimps, when compared with
      control (17 +/- 2 * 104 cells). proPhenolOxidase (proPO) activity was also
      enhanced in treated groups compared to WSSV infected shrimps. Less production of
      superoxide anion was observed in control and treated groups. Differences in the
      protein expression was analyzed in muscle tissue of control, WSSV infected and
      PHB/biosurfactant treated shrimps. Our finding suggested that partial
      substitution of feed with 2% PHB and biosurfactant showed increased rate on the
      survival of WSSV infected P. monodon which might be due to either the over
      expression/down regulation of proteins that play a vital role in enhancing the
      immune system/the progression of the disease respectively.

PMID- 29032040
TI  - Effects of dietary ginkgo biloba leaf extract on growth performance, plasma
      biochemical parameters, fish composition, immune responses, liver histology, and
      immune and apoptosis-related genes expression of hybrid grouper (Epinephelus
      lanceolatus? * Epinephelus fuscoguttatus?) fed high lipid diets.
AB  - For thousands of years, leaves from the Ginkgo biloba tree have been a common
      treatment in Chinese medicine. The present study was conducted to investigate the
      effects of dietary ginkgo biloba leaf extract (GBE) supplementation on growth
      performance, plasma biochemical parameters, fish composition, immune responses,
      liver histology, and immune and apoptosis-related genes expression of hybrid
      grouper (Epinephelus lanceolatus? * Epinephelus fuscoguttatus?) fed high lipid
      diets. A basal diet supplemented with GBE at 0, 0.50, 1.00, 2.00, 4.00 and 10.00
      g kg-1 was fed to hybrid grouper for 8 weeks. The study indicated that dietary
      GBE did not improve growth performance and feed utilization but it reduced
      intraperitoneal fat rate. There were no significant differences in condition
      factor, viscerosomatic index, hepatosomatic index, spleen index, relative gut
      length, food intake, protein deposit rate and survival among all groups (P >
      0.05). Dietary supplementation with 0.50-4.00 g GBE kg-1 diets effectively
      increased plasma HDL content and decreased plasma GLU, LDL and TG content in
      fish. Furthermore, dietary GBE had a significant effect on moisture, crude
      protein and lipid in the liver, and protein in the whole body of fish (P < 0.05).
      Dietary supplementation with 0.50-1.00 g GBE kg-1 diets effectively decreased
      occurrence rates of the hepatocyte swelling, hepatocyte vacuolization, and nuclei
      shifting to the cellular periphery cytoplasmic vacuolization, meanwhile hepatic
      antioxidant enzymes (SOD, CAT and T-AOC) activities significantly increased
      whereas MDA content significantly decreased in fish fed diets supplemented with
      GBE (P < 0.05). Moreover, dietary GBE up-regulated the expression of antioxidant
      genes (CAT, GPx and GR), immune-related genes (MHC2 and TLR3) and anti
      inflammatory cytokines (IL-10 and TGF-beta1), while dietary supplementation with
      0.50-4.00 g GBE kg-1 diets down-regulated apoptosis-related genes (p53, caspase
      9, caspase-8 and caspase-3) expression in the head kidney of hybrid grouper.
      These results indicated that hybrid grouper fed diets supplemented with GBE did
      not improve growth performance and feed utilization but it had hypolipidemic
      effects, improved hepatic antioxidant status, maintained normal liver histology
      and preserved liver function, increased immune-related genes expression and
      decreased apoptosis-related genes expression in the head kidney of hybrid
      grouper.

PMID- 29032041
TI  - Transformative therapies for rare CFTR missense alleles.
AB  - With over 1900 variants reported in the cystic fibrosis transmembrane conductance
      regulator (CFTR), enhanced understanding of cystic fibrosis (CF) genotype
      phenotype correlation represents an important and expanding area of research. The
      potentiator Ivacaftor has proven an effective treatment for a subset of
      individuals carrying missense variants, particularly those that impact CFTR
      gating. Therapeutic efforts have recently focused on correcting the basic defect
      resulting from the common F508del variant, as well as many less frequent missense
      alleles. Modest enhancement of F508del-CFTR function has been achieved by
      combining Ivacaftor with Lumacaftor, a compound that aids maturational processing
      of misfolded CFTR. Continued development of in silico and in vitro models will
      facilitate CFTR variant characterization and drug testing, thereby elucidating
      heterogeneity in the molecular pathogenesis, phenotype, and modulator
      responsiveness of CF.

PMID- 29032042
TI  - A reliable and stable method for determination of brigatinib in rat plasma by
      UPLC-MS/MS: Application to a pharmacokinetic study.
AB  - Brigatinib is the second-generation anaplastic lymphoma kinase - inhibitor in non
      small cell lung cancer and it can overcome the crizotinib-resistance.
      Chromatographic separation was carried out on an Acquity Ultra Performance Liquid
      Chromatography (UPLC) unit with a BEH C18 column (2.1mm*50mm, 1.7MUm). The mobile
      phase was composed of acetonitrile and 0.1% formic acid in water. No endogenous
      interfering compounds was discovered at retention time of brigatinib (0.56min)
      and imatinib (IS, 1.41min). MS/MS detection was performed in positive mode. And
      the MRM transitions were m/z 584.09->484.08 and m/z 494.3->394.2 for brigatinib
      and IS, respectively. This method was assessed to be stable, specificity, and no
      matrix effect in three concentrations (0.004, 0.4, 4MUg/mL). The intra-day and
      inter-day precisions were less than 11.09% and 6.43%. And intra-day and inter-day
      accuracies were ranged from -3.88% to 5.44%. The recovery of brigatinib was from
      85.26% to 96.05%. Additionally, the method had a good linearity in the range of
      0.002-5MUg/mL. The presented method was effectively implemented to determine the
      concentration of brigatinib in rat plasma.

PMID- 29032043
TI  - Fast and sensitive HPLC-MS/MS method for direct quantification of intracellular
      deoxyribonucleoside triphosphates from tissue and cells.
AB  - Deoxyribonucleoside triphosphates (dNTPs) are used in DNA synthesis and repair.
      Even slight imbalances can have adverse biological effects. This study validates
      a fast and sensitive HPLC-MS/MS method for direct quantification of intracellular
      dNTPs from tissue. Equal volumes of methanol and water were used for nucleotide
      extraction from mouse heart and gastrocnemius muscle and isolated cardiomyocytes
      followed by centrifugation to remove particulates. The resulting supernatant was
      analyzed on a porous graphitic carbon chromatography column using an elution
      gradient of ammonium acetate in water and ammonium hydroxide in acetonitrile with
      a run time of just 10min. Calibration curves of all dNTPs ranged from 62.5 to
      2500fmol injections and demonstrated excellent linearity (r2>0.99). The within
      day and between day precision, as measured by the coefficient of variation (CV
      (%)), was <25% for all points, including the lower limit of quantification
      (LLOQ). The inter-day accuracy was within 12% of expected concentration for the
      LLOQ and within 7% for all other points on the calibration curve. The intra-day
      accuracy was within 22% for the LLOQ and within 11% for all points on the curve.
      Compared to existing methods, this study presents a faster and more sensitive
      method for dNTP quantification.

PMID- 29032044
TI  - Multiplex quantitative analysis of eicosanoid mediators in human plasma and
      serum: Possible introduction into clinical testing.
AB  - Eicosanoid mediators play important roles in maintaining the physiological and
      pathophysiological homeostasis in the body. Their measurements, however, are
      rarely performed in clinical practice. In the present study, we analyzed 30
      varieties of eicosanoid mediators that were detectable in human plasma and serum
      collected from healthy donors, using liquid chromatography-tandem mass
      spectrometry from the viewpoint of the clinical application of the multiplex
      quantitation of eicosanoid mediators. Wider variety of eicosanoid mediators were
      detected in serum (27 out of 30) than in plasma (14 out of 30), since the serum
      was thought to contain lipid mediators released from activated platelets. Larger
      inter-individual variations were observed in the plasma and serum eicosanoid
      levels. On the other hand, the concentrations of eicosanoids were not affected by
      the platelet count but were affected by the concentration of arachidonic acid
      (AA) within the reference interval (17.4-40.5*1010/L). When serum samples from
      patients with hematological disorders were analyzed, the concentrations of AA
      were positively correlated with the platelet count. When the patients underwent
      ASA therapy, a marked decrease in the concentrations of thromboxane B2 (TXB2) and
      12-hydroxyl-heptadecatrienoic acid (12-HHT) was observed. Considering the
      availability of serum samples in clinical settings, the serum analysis of
      eicosanoids may be clinically useful.

PMID- 29032045
TI  - A sensitive biosensor using double-layer capillary based immunomagnetic
      separation and invertase-nanocluster based signal amplification for rapid
      detection of foodborne pathogen.
AB  - Combining double-layer capillary based high gradient immunomagnetic separation,
      invertase-nanocluster based signal amplification and glucose meter based signal
      detection, a novel biosensor was developed for sensitive and rapid detection of
      E. coli O157:H7 in this study. The streptavidin modified magnetic nanobeads
      (MNBs) were conjugated with the biotinylated polyclonal antibodies against E.
      coli O157:H7 to form the immune MNBs, which were captured by the high gradient
      magnetic field in the double-layer capillary to specifically separate and
      efficiently concentrate the target bacteria. Calcium chloride was used with the
      monoclonal antibodies against E. coli O157:H7 and the invertase to form the
      immune invertase-nanoclusters (INCs), which were used to react with the target
      bacteria to form the MNB-bacteria-INC complexes in the capillary. The sucrose was
      then injected into the capillary and catalyzed by the invertase on the complexes
      into the glucose, which was detected using the glucose meter to obtain the
      concentration of the glucose for final determination of the E. coli O157:H7 cells
      in the sample. A linear relationship between the readout of the glucose meter and
      the concentration of the E. coli O157:H7 cells (from 102 to 107 CFU/mL) was found
      and the lower detection limit of this biosensor was 79 CFU/mL. This biosensor
      might be extended for the detection of other foodborne pathogens by changing the
      antibodies and has shown the potential for the detection of foodborne pathogens
      in a large volume of sample to further increase the sensitivity.

PMID- 29032047
TI  - Reactivation of peroxidase activity in human saliva samples by polyphenols.
AB  - OBJECTIVES: The enzyme lactoperoxidase (LPO), which is released into several body
      fluids like saliva, is an essential part to maintain the oral bacterial
      homeostasis by catalysing the oxidation of thiocyanate (SCN-) to hypo-thiocyanite
      (-OSCN). The formation of unreactive redox intermediates (like Compound II) leads
      to a decreased pseudo-halogenating enzyme activity, which is associated with a
      higher risk for oral infections. According to former studies with bovine LPO
      selected flavonoids were tested in respect to their potential to reactivate the
      enzymatic activity in a more physiological, human salivary system. DESIGN: Saliva
      samples from healthy donors were collected and characterized by using several gel
      staining methods and immunoblotting. Afterwards kinetic measurements were
      performed by applying the TNB-assay to evaluate the pseudo-halogenating salivary
      peroxidase (SAPX) activity. The measurements were performed in the presence of
      excess H2O2 to simulate pro-inflammatory conditions. Moreover selected flavonoids
      or an ethanolic extract of Tormentillae rhizoma were applied to test their
      regenerating effect on the LPO-derived -OSCN production. RESULTS: Despite the
      complex protein composition of the collected saliva samples, an SAPX-derived
      pseudo-halogenating activity could be identified. The -OSCN regenerating effects
      of the tested polyphenols were completely comparable to previous in vitro
      experiments with bovine LPO. Thus, we could show that phenolic substances are
      suitable to regenerate the peroxidase activity in human saliva samples after H2O2
      induced inactivation. CONCLUSION: The studies provide new insights into the
      effect of pharmaceutical relevant polyphenols on salivary peroxidase activity and
      thus, suggest this enzyme as a new target for the prevention and therapy of oral
      inflammatory diseases.

PMID- 29032046
TI  - Past, present, and future of genetic research in borderline personality disorder.
AB  - Borderline Personality Disorder (BPD) is a major mental illness with a lifetime
      prevalence of approximately 1-3%, characterized by a persistent pattern of
      instability in relationships, mood, impulse regulation, and sense of self. This
      results in impulsive self-damaging behavior, high suicide rates, and severe
      functional impairment. BPD has a complex, multifactorial etiology, resulting from
      an interaction among genetic and environmental substrates, and has moderate to
      high heritability based on twin and family studies. However, our understanding of
      the genetic architecture of BPD is very limited. This is a critical obstacle
      since genetics can pave the way for identifying new treatment targets and
      developing preventive and disease-modifying pharmacological treatments which are
      currently lacking. We review genetic studies in BPD, with a focus on limitations
      and challenges and future directions. Genetic research in BPD is still in its
      very early stages compared to other major psychiatric disorders. Most early
      genetic studies in BPD were non-replicated association studies in small samples,
      focused on single candidate genes. More recently, there has been one genome-wide
      linkage study and a genome-wide association study (GWAS) of subclinical BPD
      traits and a first GWAS in a relatively modest sample of patients fulfilling full
      diagnostic criteria for the disorder. Although there are adequate animal models
      for some of the core dimensions of BPD, there is a lack of translational research
      including data from animal models in BPD. Research in more pioneering fields,
      such as imaging genetics, deep sequencing and epigenetics, holds promise for
      elucidating the pathophysiology of BPD and identifying new treatment targets.

PMID- 29032048
TI  - Cytokine profile changes in gingival crevicular fluid after placement different
      brackets types.
AB  - OBJECTIVE: The aim of this study was to examine the relationship between bracket
      design and ratio of five proinflammatory cytokine, in gingival crevicular fluid
      (GCF), and bacterial adhesion without tooth movement influence. DESIGN: The
      sample was comprised of 20 participants, aged 11 to 15 years old (mean age: 13.3
      years+/-1.03). A conventional GeminiTM metallic bracket and two self-ligating
      brackets, In-Ovation(r)R and SmartClipTM, were bonded to the maxillary incisors
      and canines. GCF was collected using a standard filter paper strip before and
      60days after bonding. The cytokine levels (IL-12, IL-1alpha, IL-1beta, IL-6 and
      TNF-alpha) were performed by the LUMINEX assay. The levels of the red and orange
      bacterial complexes were analyzed by the Checkerboard DNA-DNA hybridization. The
      data of cytokine and bacterial complexes were carried out using the non
      parametric tests at 5% of significance level. RESULTS: Increased cytokine levels
      were observed. However, only the SmartClipTM group showed a significantly
      increased level of TNF-alpha (p=0.046). The SmartClipTM brackets group presented
      higher levels of red complex bacteria. CONCLUSIONS: The bracket design affected
      cytokine levels and bacterial adhesion since it was observed that the
      proinflammatory cytokines released in GCF to the SmartClipTM group showed an
      increase in the TNF-alpha levels associated with higher bacterial levels, which
      possibly represents greater inflammatory potential. Thereby, the bracket design
      should be considered in patients with risk of periodontal disease and root
      resorption.

PMID- 29032049
TI  - A periodic two-patch SIS model with time delay and transport-related infection.
AB  - In this paper, we propose a periodic SIS epidemic model with time delay and
      transport-related infection in a patchy environment. The basic reproduction
      number R0 is derived which determines the global dynamics of the model system: if
      R0 < 1, the disease-free periodic state is globally attractive while there exists
      at least one positive periodic state and the disease persists if R0 > 1.
      Numerical simulations are performed to confirm the analytical results and to
      explore the dependence of R0 on the transport-related infection parameters and
      the amplitude of fluctuations.

PMID- 29032050
TI  - Positive predictive value estimates for cell-free noninvasive prenatal screening
      from data of a large referral genetic diagnostic laboratory.
AB  - BACKGROUND: Since its debut in 2011, cell-free fetal DNA screening has undergone
      rapid expansion with respect to both utilization and coverage. However,
      conclusive data regarding the clinical validity and utility of this screening
      tool, both for the originally included common autosomal and sex-chromosomal
      aneuploidies as well as the more recently added chromosomal microdeletion
      syndromes, have lagged behind. Thus, there is a continued need to educate
      clinicians and patients about the current benefits and limitations of this
      screening tool to inform pre- and posttest counseling, pre/perinatal decision
      making, and medical risk assessment/management. OBJECTIVE: The objective of this
      study was to determine the positive predictive value and false-positive rates for
      different chromosomal abnormalities identified by cell-free fetal DNA screening
      using a large data set of diagnostic testing results on invasive samples
      submitted to the laboratory for confirmatory studies. STUDY DESIGN: We tested 712
      patient samples sent to our laboratory to confirm a cell-free fetal DNA screening
      result, indicating high risk for a chromosome abnormality. We compiled data from
      all cases in which the indication for confirmatory testing was a positive cell
      free fetal DNA screen, including the common trisomies, sex chromosomal
      aneuploidies, microdeletion syndromes, and other large genome-wide copy number
      abnormalities. Testing modalities included fluorescence in situ hybridization, G
      banded karyotype, and/or chromosomal microarray analysis performed on chorionic
      villus samples, amniotic fluid, or postnatally obtained blood samples. Positive
      predictive values and false-positive rates were calculated from tabulated data.
      RESULTS: The positive predictive values for trisomy 13, 18, and 21 were
      consistent with previous reports at 45%, 76%, and 84%, respectively. For the
      microdeletion syndrome regions, positive predictive values ranged from 0% for
      detection of Cri-du-Chat syndrome and Prader-Willi/Angelman syndrome to 14% for
      1p36 deletion syndrome and 21% for 22q11.2 deletion syndrome. Detection of sex
      chromosomal aneuploidies had positive predictive values of 26% for monosomy X,
      50% for 47,XXX, and 86% for 47,XXY. CONCLUSION: The positive predictive values
      for detection of common autosomal and sex chromosomal aneuploidies by cell-free
      fetal DNA screening were comparable with other studies. Identification of
      microdeletions was associated with lower positive predictive values and higher
      false-positive rates, likely because of the low prevalence of the individual
      targeted microdeletion syndromes in the general population. Although the obtained
      positive predictive values compare favorably with those seen in traditional
      screening approaches for common aneuploidies, they highlight the importance of
      educating clinicians and patients on the limitations of cell-free fetal DNA
      screening tests. Improvement of the cell-free fetal DNA screening technology and
      continued monitoring of its performance after introduction into clinical practice
      will be important to fully establish its clinical utility. Nonetheless, our data
      provide valuable information that may aid result interpretation, patient
      counseling, and clinical decision making/management.

PMID- 29032051
TI  - Bowel endometriosis: diagnosis and management.
AB  - The most common location of extragenital endometriosis is the bowel. Medical
      treatment may not provide long-term improvement in patients who are symptomatic,
      and consequently most of these patients may require surgical intervention. Over
      the past century, surgeons have continued to debate the optimal surgical approach
      to treating bowel endometriosis, weighing the risks against the benefits. In this
      expert review we will describe how the recommended surgical approach depends
      largely on the location of disease, in addition to size and depth of the lesion.
      For lesions approximately 5-8 cm from the anal verge, we encourage conservative
      surgical management over resection to decrease the risk of short- and long-term
      complications.

PMID- 29032052
TI  - DFT, QTAIM, and NBO studies on the trimeric interactions in the protrusion domain
      of a piscine betanodavirus.
AB  - Crystal structure of the protrusion domain (P-domain) of the grouper nervous
      necrosis virus (GNNV) shows the presence of three-fold trimeric protrusions with
      two asymmetrical calcium cations along the non-crystallographic three-fold axis.
      The trimeric interaction natures of the interacting residues and the calcium
      cations with the neighboring residues within the trimeric interface have been
      studied by the quantum theory of atoms in molecules (QTAIM) and natural bond
      orbital (NBO) analyses in the framework of the density-functional theory (DFT)
      approach. The results revealed that residues Leu259, Val274, Trp280, and Gln322
      of subunit A, Arg261, Asp275, Ala277, and Gln322 of subunit B, Leu259, Asp260,
      Arg261, Ala277, Val278, and Leu324 of subunit C are the main residues involved in
      the trimeric interactions. Charge-dipole, dipole-dipole, and hydrogen bonding
      interactions make the significant contributions to these trimeric interactions.
      Among different interacting residues within trimeric interface, residue pair
      Arg261 B-Leu259C forms the strongest hydrogen bond inside the interface between
      subunits B and C. It was also found that calcium cations interact with residues
      Asp273, Val274, and Asp275 of subunits A, B, and C through charge-charge and
      charge transfer interactions.

PMID- 29032053
TI  - Effects of combination of change in visceral fat and thigh muscle mass on the
      development of type 2 diabetes.
AB  - AIM: We investigated the association between combined changes of visceral fat and
      thigh muscle over 5 years and incident type 2 diabetes in a prospective study of
      Japanese Americans. METHODS: We followed 420 nondiabetic Japanese American
      subjects for 5 years and assessed visceral fat and thigh muscle by computed
      tomography (CT) at baseline and at 5 years. We categorized study subjects into 4
      body composition change groups: visceral fat loss/thigh muscle gain (VF-loss/TM
      gain), visceral fat loss/thigh muscle loss (VF-loss/TM-loss), visceral fat
      gain/thigh muscle gain (VF-gain/TM-gain), and visceral fat gain/thigh muscle loss
      (VF-gain/TM-loss) by combining changes from baseline in CT measured visceral fat
      and estimated thigh muscle areas. We fit a logistic regression model to examine
      the association between body composition categories and the development of
      incident type 2 diabetes at 5 years. RESULTS: Cumulative incidence of type 2
      diabetes was 9.8% at 5 years. VF-gain/TM-gain and VF-loss/TM-loss groups had
      higher risk for incident type 2 diabetes in a model adjusted for age, sex, family
      history of diabetes, and body mass index compared to VF-loss/TM-gain group as the
      reference category (OR=6.83 (1.85-25.17), 4.55 (1.06-19.48), respectively).
      However, the VF-gain/TM-loss group did not show a significant association with
      the odds of incident diabetes (3.24; 95% CI. 0.78-13.47). CONCLUSIONS: Concordant
      gain or loss in visceral fat and thigh muscle was related to higher risk of
      incident type 2 diabetes compared to the reference combination of loss of
      visceral fat and gain of thigh muscle in Japanese Americans.

PMID- 29032054
TI  - Role of ethanolic extract of Bacopa monnieri against 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) induced mice model via inhibition of apoptotic pathways
      of dopaminergic neurons.
AB  - Parkinson's disease (PD) is a neurodegenerative disease which causes rigidity,
      resting tremor and postural instability. The neuroprotective effects of an
      ethanolic extract of Bacopa monnieri (BM) were evaluated in a Parkinsonian mice
      model induced by the MPTP. The present study investigates the mechanisms of
      neuroprotection elicited by BM, an herb traditionally recognized by the Indian
      system of medicine, Ayurveda. An ethanolic extract of BM was co-treated with the
      MPTP induced mouse model of PD and was shown to significantly rescue the motor
      behaviour (Rotarod, Grip Strength and Foot Printing test). Furthermore, on
      biochemical parameters too BM significantly showed protective effect as Catalase,
      LPO, Nitrite, SOD, GR, GPx parameters showed marked improvement and levels of
      Dopamine, DOPAC and HVA were enhanced significantly. There was a significant
      reduction in tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra
      (SN) in MPTP treated group, which was considerably restored by the use of BM
      extract. BM also facilitated neuroprotection by creating an anti-apoptotic
      environment indicated by reduced apoptotic (Bax and caspase-3) and increased
      levels of anti-apoptotic (Bcl2) protein expression, respectively. Altogether, the
      present study suggests that BM treatment provides nigrostriatal dopaminergic
      neuroprotection against MPTP induced Parkinsonism by the modulation of oxidative
      stress and apoptotic machinery possibly accounting for the behavioural effects.

PMID- 29032055
TI  - Microbiological characterisation of Klebsiella pneumoniae isolates causing
      bloodstream infections from five tertiary hospitals in Beijing, China.
AB  - OBJECTIVES: Klebsiella pneumoniae is prevalent in China. Little is known about
      the microbiological characteristics of clinical K. pneumoniae isolates causing
      bloodstream infections (BSIs). METHODS: BSI-causing K. pneumoniae (BSI-Kpn) were
      collected from five tertiary-care hospitals in Beijing. Genetic relatedness was
      analysed by PFGE, antimicrobial susceptibility was determined by agar dilution,
      and sequence types (STs) were evaluated by MLST. Hypermucoviscosity (HV)
      phenotype was identified by positive string test. Carbapenemase, capsular
      serotype and HV-associated genes were detected by PCR. RESULTS: A total of 219
      non-duplicate BSI-Kpn were collected from December 2013 to December 2014 and were
      categorised into 203 types (strains) with unique PFGE patterns. Among 203 BSI
      Kpn, 105 STs were identified. Overall, ST11 and ST23 were the predominant clones
      (14 strains each; 6.9%), followed by ST412 (n=13), ST37 (n=9), ST65 (n=7), ST15
      (n=6), ST86 (n=6), ST592 (n=5) and ST29 (n=4). There were 74 STs containing only
      a single strain. Approximately 8.4% (17/203) of the strains exhibited carbapenem
      resistance, most producing KPC carbapenemase. The majority (75.9%; 154/203) of
      isolates were associated with non-K1/K2/K5/K20/K54/K57 serotypes. Only 16.3%
      (33/203) of the strains had K1/K2 serotypes. A total of 66 (32.5%) of the BSI-Kpn
      strains exhibited a HV phenotype. rmpA was a predominant factor in determining a
      HV phenotype. CONCLUSIONS: The majority of BSI-Kpn strains exhibited high genetic
      diversity and low resistance to commonly used antimicrobials. The specific
      capsular serotype and HV phenotype were not major features of BSI-Kpn strains in
      China.

PMID- 29032056
TI  - In silico approaches to RNA aptamer design.
AB  - RNA aptamers are ribonucleic acids that bind to specific target molecules. An RNA
      aptamer for a disease-related protein has great potential for development into a
      new drug. However, huge time and cost investments are required to develop an RNA
      aptamer into a pharmaceutical. Recently, SELEX combined with high-throughput
      sequencers (i.e., HT-SELEX) has been widely used to select candidate RNA aptamers
      that bind to a target protein with high affinity and specificity. After candidate
      selection, further optimizations such as shortening and modifying candidate
      sequences are performed. In these steps, in silico approaches are expected to
      reduce the time and cost associated with aptamer drug development. In this
      article, we review existing in silico approaches to RNA aptamer development,
      including a method for ranking the candidates of RNA aptamers from HT-SELEX data,
      clustering a huge number of aptamer sequences, and finding motifs amidst a set of
      significant RNA aptamers. It is expected that further studies in addition to
      these methods will be utilized for in silico RNA aptamer design, permitting a
      minimal number of experiments to be performed through the utilization of
      sophisticated computational methods.

PMID- 29032057
TI  - The Hog1p kinase regulates Aft1p transcription factor to control iron
      accumulation.
AB  - Iron acquisition systems have to be tightly regulated to assure a continuous
      supply of iron, since it is essential for survival, but simultaneously to prevent
      iron overload that is toxic to the cells. In budding yeast, the low-iron sensing
      transcription factor Aft1p is a master regulator of the iron regulon. Our
      previous work revealed that bioactive sphingolipids modulate iron homeostasis as
      yeast cells lacking the sphingomyelinase Isc1p exhibit an upregulation of the
      iron regulon. In this study, we show that Isc1p impacts on iron accumulation and
      localization. Notably, Aft1p is activated in isc1Delta cells due to a decrease in
      its phosphorylation and an increase in its nuclear levels. Consistently, the
      expression of a phosphomimetic version of Aft1p-S210/S224 that favours its
      nuclear export abolished iron accumulation in isc1Delta cells. Notably, the Hog1p
      kinase, homologue of mammalian p38, interacts with and directly phosphorylates
      Aft1p at residues S210 and S224. However, Hog1p-Aft1p interaction decreases in
      isc1Delta cells, which likely contributes to Aft1p dephosphorylation and
      consequently to Aft1p activation and iron overload in isc1Delta cells. These
      results suggest that alterations in sphingolipid composition in isc1Delta cells
      may impact on iron homeostasis by disturbing the regulation of Aft1p by Hog1p. To
      our knowledge, Hog1p is the first kinase reported to directly regulate Aft1p,
      impacting on iron homeostasis.

PMID- 29032058
TI  - Cross state-dependency of learning between arachidonylcyclopropylamide (ACPA) and
      muscimol in the mouse dorsal hippocampus.
AB  - The aim of the present study was to examine cross state-dependent learning
      between ACPA (a selective cannabinoid CB1 receptor agonist) and muscimol (a
      selective GABAA receptor agonist) in the step-down inhibitory avoidance learning
      task. The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally
      cannulated, and all drugs were microinjected into the intended sites of
      injection. Post-training and/or pre-test administration of ACPA (1 and 2ng/mouse)
      dose-dependently induced amnesia. Pre-test microinjection of the same doses of
      ACPA reversed the post-training ACPA-induced amnesia. This event has been named
      ACPA state-dependent learning (SDL). Post-training and/or pre-test microinjection
      of muscimol (0.05 and 0.1MUg/mouse) dose-dependently induced amnesia. Pre-test
      administration of the same doses of muscimol reversed the post-training muscimol
      induced amnesia, suggesting muscimol SDL. The amnesia induced by post-training
      administration of ACPA was reversed by pre-test administration of muscimol (0.05
      and 0.1MUg/mouse). Furthermore, the pre-test microinjection of muscimol (0.025
      and 0.05MUg/mouse) with an ineffective dose of ACPA (0.5ng/mouse) significantly
      restored memory retrieval and induced ACPA SDL. In another series of experiments,
      the amnesia induced by post-training administration of muscimol was reversed by
      pre-test administration of ACPA (1 and 2ng/mouse). Moreover, pre-test
      microinjection of ACPA (0.5 and 1ng/mouse) with an ineffective dose of muscimol
      (0.025MUg/mouse) significantly restored memory retrieval and induced muscimol
      SDL. It is important to note that pre-test intra-CA1 injection of a selective
      GABAA receptor antagonist, bicuculline (0.125 and 0.25MUg/mouse), 5min before the
      administration of muscimol (0.1MUg/mouse) or ACPA (2ng/mouse) dose-dependently
      inhibited muscimol- and ACPA-induced SDL, respectively. Pre-test intra-CA1
      administration of bicuculline (0.0625, 0.125 and 0.25MUg/mouse) by itself did not
      affect memory retention. In conclusion, the data strongly revealed a cross SDL
      among ACPA and muscimol in the dorsal hippocampal CA1 regions.

PMID- 29032060
TI  - Emerging Therapeutics for the Control of Chronic Graft-versus-Host Disease.

PMID- 29032061
TI  - Toward Individualizing Conditioning Regimens in Reduced-Intensity
      Transplantation.

PMID- 29032059
TI  - Is the adaptive immune response in murine Trypanosoma cruzi infection influenced
      by zinc supplementation?
AB  - Chagas disease afflicts 7 to 8 million people worldwide and congenital Chagas'
      disease usually leads to changes in the maternal environment, culminating in
      fetal adaptations. Several articles have described the importance of
      micronutrients on pregnancy, which is sensitive to infections. In Trypanosoma
      cruzi endemic regions, the Chagas disease is aggravated by the lack of
      micronutrients in an average diet, to which pregnant women are more susceptible.
      The aim of this study was to evaluate distinct T cells phenotypes and
      intracellular cytokines by flow cytometry in pregnant Wistar rats under zinc
      therapy during experimental Chagas' disease. Twenty female Wistar rats were
      infected with 1*105 blood trypomastigotes (Y strain) and 30days after infection
      the animals were mated and grouped: pregnant infected (PI-n=5), pregnant
      infected/zinc supplied (PIZ-n=5), pregnant control (PC-n=5), control/zinc
      supplied (PCZ-n=5). Zinc supplementation: 20mg of zinc/Kg/day (gavage) for 18days
      followed by euthanasia. The immune parameters showed: decreased percentages of
      CD62LlowCD44high surface marker for infected and treated group (PIZ) when
      compared to PI (p<0.05). Concerning to T regulatory cells (Treg cells), a
      significantly lower percentage of splenic Treg cells was found in the infected
      and treated group (PIZ) as compared to the PI group (p<0.05). The expression of
      the co-stimulatory molecule CD28+ displayed a significant reduced percentage in
      TCD8+ for infected and zinc treated group (PIZ) as compared to (PI). The
      percentages of CD4+/CD11a+ T cells subsets were lower on PIZ as compared to PI.
      Concerning to CD45RA+ (B lymphocytes) analysis, infected pregnant and treated
      group (PIZ) showed a significant decrease in CD45RA percentage when compared to
      (PI) (p<0.05). The intracellular cytokine profiles for TCD4+ and TCD8+ producing
      IL-4 and IFN-gamma revealed that zinc treated and untreated infected pregnant
      group (PI and PIZ) displayed increased cytokines concentrations as compared to
      zinc treated and untreated pregnant controls (PC and PCZ). Our data revealed the
      involvement of zinc as a signaling molecule in the modulation of the inflammatory
      process and immune response which occurs during pregnancy of T. cruzi infected
      rats. Zinc acted in a dual fashion, modulating the host's immune response in a
      way to protect the organism against the deleterious effects of the infection and
      an overwhelming pro-inflammatory response during pregnancy.

PMID- 29032063
TI  - Guidelines About Opportunistic Salpingectomy, IVF, and the Practical Side - In
      Response.

PMID- 29032062
TI  - Virus-Specific T Cells: Broadening Applicability.
AB  - Virus infection remains an appreciable cause of morbidity and mortality after
      hematopoietic stem cell transplantation (HSCT). Although pharmacotherapy and/or
      antibody therapy may help prevent or treat viral disease, these drugs are
      expensive, toxic, and often ineffective due to primary or secondary resistance.
      Further, effective treatments are limited for many infections (eg, adenovirus, BK
      virus), which are increasingly detected after alternative donor transplants.
      These deficiencies in conventional therapeutics have increased interest in an
      immunotherapeutic approach to viral disorders, leading to adoptive transfer of
      virus-specific cytotoxic T lymphocytes (VSTs), which can rapidly reconstitute
      antiviral immunity post-transplantation without causing graft-versus-host
      disease. This review will explore how the VST field has improved outcomes for
      many patients with life-threatening viral infections after HSCT, and how to
      broaden applicability beyond the "patient-specific" products, as well as
      extending to other viral diseases even outside the context of HSCT.

PMID- 29032064
TI  - Laparoscopic and Robotic-Assisted Hysterectomy for Uterine Leiomyomas: A
      Comparison of Complications and Costs.
AB  - OBJECTIVE: Robotic surgery is increasingly being used for treatment of malignant
      and benign gynaecologic diseases. The purpose of our study is to compare patient
      perioperative complications and costs of laparoscopic versus robotic-assisted
      hysterectomy for uterine leiomyomas. METHODS: A retrospective cohort study using
      the Nationwide Inpatient Sample database from the United States was conducted,
      comparing patients who underwent robotic-assisted hysterectomy and laparoscopic
      hysterectomy (total laparoscopic hysterectomy and laparoscopic-assisted vaginal
      hysterectomy) for uterine fibroids between 2008 and 2012. Baseline
      characteristics were compared between the two groups, and logistic regression was
      used to compare postoperative outcomes between laparoscopic and robotic
      approaches. Direct costs were compared between the two groups using linear
      regression models. RESULTS: Over a five-year period, the total number of
      hysterectomies performed increased. Patients undergoing robotic hysterectomy were
      older and had more comorbidities. In adjusted analyses, women who underwent
      robotic surgery were more likely to have respiratory failure (0.71% vs. 0.39%; P
      < 0.0108), postoperative fever (1.05% vs. 0.67%, P < 0.0002), and ileus (1.76%
      vs. 1.3%; P < 0.0060), and less likely to require transfusions (3.4% vs. 3.96%; P
      < 0.0037). Robotic surgery was consistently more expensive, with a median cost of
      $33 928.00 compared with $23 753.00 for laparoscopic hysterectomy. CONCLUSION:
      While there are only slight differences in postoperative complications between
      laparoscopic-assisted hysterectomy and robotic-assisted hysterectomy, robotic
      assisted hysterectomy is associated with considerably greater direct costs.
      Unless specific indications for robotic-assisted hysterectomy exist, laparoscopic
      assisted hysterectomy should be the preferred approach for minimally invasive
      surgical treatment of leiomyomas.

PMID- 29032065
TI  - Guidelines on Opportunistic Salpingectomy and IVF.

PMID- 29032066
TI  - Standardization of Laparoscopic Operative Reporting: Improving Gynaecological
      Surgeon Communication.
AB  - OBJECTIVE: No standardization of quality of operative reporting currently exists,
      and this represents a missed opportunity for communication among health care
      providers. This study proposed a method to improve operative notes by structuring
      the findings by six anatomical zones of the pelvis. Objective I was to validate
      the method of documenting six zones of the pelvis by using intraoperative
      photography. Objective II was to compare this method with dictations from
      operative reports created before introducing this method. METHODS: This
      retrospective cohort study evaluated pre- and post-intervention results of using
      six zones to guide operative reporting. Reports were collected from participating
      surgeons and were scored using a validated scoring tool. Each participant was
      taught to photograph six zones and use the zones in the operative report. Pre-
      and post-intervention cases were compared using generalized linear mixed models.
      RESULTS: Scores of study participants using the zones were significantly higher
      than those without (P <0.0001). Surgeons showed an ability to improve their
      reporting. The detail illustrated in the cases was qualitatively richer, and the
      anatomy within the six zones was referenced more frequently. CONCLUSION: Compared
      with reports without the technique, incorporating the six zones greatly enhances
      operative reporting and likely would improve communication among care providers.
      More reliable communication of intraoperative findings has the potential to
      enhance the value of laparoscopy greatly as a diagnostic tool across
      gynaecological subspecialties.

PMID- 29032067
TI  - A Rare Case of Gestational Choriocarcinoma Presenting as Cornual Ectopic
      Pregnancy.
AB  - BACKGROUND: Choriocarcinoma associated with cornual pregnancy is extremely rare.
      To our knowledge, only three other cases have been reported in the literature.
      CASE: A 38-year-old woman was found to have a left cornual ectopic pregnancy on
      ultrasound after presenting with abdominal pain, irregular vaginal bleeding, and
      a positive pregnancy test. Laparoscopy confirmed the diagnosis and she underwent
      total abdominal hysterectomy. Three weeks later, she presented with vaginal
      bleeding. A solid ulcerating lesion was found arising from the vaginal wall and
      biopsy revealed metastatic gestational choriocarcinoma. CONCLUSION: Careful
      histopathological examination of the surgical specimen and diligent monitoring of
      beta-human chorionic gonadotropin to zero is crucial to prevent potentially
      missing this very malignant, but highly curable disease. Early systemic
      metastases are common and presentation can include bleeding from vaginal
      metastases.

PMID- 29032068
TI  - CRISPR Gene Editing Should Be Allowed in Canada, But Under What Circumstances?

PMID- 29032069
TI  - Woman's Pre-Conception Evaluation: Genetic and Fetal Risk Considerations for
      Counselling and Informed Choice.
AB  - OBJECTIVE: To inform reproductive and other health care providers about genetic
      and fetal risk information to consider during a woman/couples' pre-conception
      evaluation, including considerations for genetic risk assessment, genetic
      screening, or testing to allow for improved counselling and informed choice.
      OPTIONS: This genetic information can be used for patient education, planning,
      and possible pre-conception and/or prenatal testing. OUTCOMES: This information
      may allow improved risk assessment for pre-conception counselling for individual
      patients and their families. EVIDENCE: PubMed or Medline and the Cochrane
      Database were searched in May 2017 using appropriate key words ("pre-conception,"
      "genetic disease," "maternal," "family history," "genetic," "health risk,"
      "genetic health surveillance," "prenatal screening," "prenatal diagnosis," "birth
      defects," and "teratogen"). Grey (unpublished) literature was identified through
      searching the websites of health technology assessment and health technology
      assessment-related agencies, clinical practice guideline collections, and
      national and international medical specialty societies. BENEFITS, HARMS, AND
      COSTS: The benefits for the patient and her family include an increased
      understanding of relevant genetic risk pre-conception and in early pregnancy, and
      better pregnancy outcomes as a result of use of the information. The harm
      includes potential increased anxiety or psychological stress associated with the
      possibility of identifying genetic risks. VALIDATION: The evidence obtained was
      peer-reviewed by the Genetics Committee of The Society of Obstetricians and
      Gynaecologists of Canada. Consideration for Care Statements For this review
      article, the Consideration for Care Statements use the GRADE strength and quality
      as it is comparable for the clinician and the patient/public user. [GRADE from
      the Canadian Task Force on Preventive Health Care (www.canadiantaskforce.ca). For
      clinicians, Strong = The recommendation would apply to most individuals. Formal
      discussion aids are not likely to be needed to help individuals make decisions
      consistent with their values and preferences. For patients/public, Strong = We
      believe most people in this situation would want the recommended course of
      actions and only a small number would not. Quality of evidence (High, Moderate,
      Low) based on the confidence that the true effect lies close to that of the
      estimate of the effect.] Conclusion Pre-conception planning is presently
      underutilized by both patients and providers. Pre-conception genetic assessment
      is only a part of the counselling, education, and health management change that
      can improve perinatal and maternal morbidity and mortality. A published
      literature review on pre-conception genetic counselling identified mainly
      clinical cohort studies, surveys, and expert opinion with no RCTs. There is
      strong support for pre-conception counselling and moderate quality based on the
      understanding that most individuals would support and use pre-conception
      counselling when choice, timing, and ease of access is considered.

PMID- 29032070
TI  - The Practical Side of Opportunistic Salpingectomy.

PMID- 29032071
TI  - Comparing intestinal versus diffuse gastric cancer using a PEFF-oriented
      proteomic pipeline.
AB  - : Gastric cancer is the fifth most common malignant neoplasia and the third
      leading cause of cancer death worldwide. Mac-Cormick et al. recently showed the
      importance of considering the anatomical region of the tumor in proteomic gastric
      cancer studies; more differences were found between distinct anatomical regions
      than when comparing healthy versus diseased tissue. Thus, failing to consider the
      anatomical region could lead to differential proteins that are not disease
      specific. With this as motivation, we compared the proteomic profiles of
      intestinal and diffuse adenocarcinoma from the same anatomical region, the
      corpus. To achieve this, we used isobaric labeling (iTRAQ) of peptides, a 10-step
      HILIC fractionation, and reversed-phase nano-chromatography coupled online with a
      Q-Exactive Plus mass spectrometer. We updated PatternLab to take advantage of the
      new Comet-PEFF search engine that enables identifying post-translational
      modifications and mutations included in neXtProt's PSI Extended FASTA Format
      (PEFF) metadata. Our pipeline then uses a text-mining tool that automatically
      extracts PubMed IDs from the proteomic result metadata and drills down keywords
      from manuscripts related with the biological processes at hand. Our results
      disclose important proteins such as apolipoprotein B-100, S100 and 14-3-3
      proteins, among many others, highlighting the different pathways enriched by each
      cancer type. SIGNIFICANCE: Gastric cancer is a heterogeneous and multifactorial
      disease responsible for a significant number of deaths every year. Despite the
      constant improvement of surgical techniques and multimodal treatments, survival
      rates are low, mostly due to limited diagnostic techniques and late symptoms.
      Intestinal and diffuse types of gastric cancer have distinct clinical and
      pathological characteristics; yet little is known about the molecular mechanisms
      regulating these two types of gastric tumors. Here we compared the proteomic
      profile of diffuse and intestinal types of gastric cancer from the same
      anatomical location, the corpus, from four male patients. This methodological
      design aimed to eliminate proteomic variations resulting from comparison of
      tumors from distinct anatomical regions. Our PEFF-tailored proteomic pipeline
      significantly increased the identifications as when compared to previous versions
      of PatternLab.

PMID- 29032072
TI  - Oxidative stress prediction: A preliminary approach using a response surface
      based technique.
AB  - A response surface was built to predict the lipid peroxidation level, generated
      in an iron-ascorbate in vitro model, of any organ, which is correlated with the
      oxidative stress injury in biological membranes. Oxidative stress studies are
      numerous, usually performed on laboratory animals. However, ethical concerns
      require validated methods to reduce the use of laboratory animals. The response
      surface described here is a validated method to replace animals. Tissue samples
      of rabbit liver, kidney, heart, skeletal muscle and brain were oxidized with
      different concentrations of FeCl3 (0.1 to 8mM) and ascorbate (0.1mM), during
      different periods of time (0 to 90min) at 37 degrees C. Experimental data
      obtained, with lipid content and antioxidant activity of each organ, allowed
      constructing a multidimensional surface capable of predicting, by interpolation,
      the lipid peroxidation level of any organ defined by its antioxidant activity and
      fat content, when exposed to different oxidant conditions. To check the
      predictive potential of the technique, two more experiments were carried out.
      First, in vitro oxidation data from lung tissue were collected. Second, the
      antioxidant capacity of kidney homogenates was modified by adding melatonin.
      Then, the response surface generated could predict lipid peroxidation levels
      produced in these new situations. The potential of this technique could be
      reinforced using collaborative databases to reduce the number of animals in
      experimental procedures.

PMID- 29032073
TI  - A Compendium of Co-regulated Protein Complexes in Breast Cancer Reveals
      Collateral Loss Events.
AB  - Protein complexes are responsible for the bulk of activities within the cell, but
      how their behavior and abundance varies across tumors remains poorly understood.
      By combining proteomic profiles of breast tumors with a large-scale protein
      protein interaction network, we have identified a set of 285 high-confidence
      protein complexes whose subunits have highly correlated protein abundance across
      tumor samples. We used this set to identify complexes that are reproducibly under
      or overexpressed in specific breast cancer subtypes. We found that mutation or
      deletion of one subunit of a co-regulated complex was often associated with a
      collateral reduction in protein expression of additional complex members. This
      collateral loss phenomenon was typically evident from proteomic, but not
      transcriptomic, profiles, suggesting post-transcriptional control. Mutation of
      the tumor suppressor E-cadherin (CDH1) was associated with a collateral loss of
      members of the adherens junction complex, an effect we validated using an
      engineered model of E-cadherin loss.

PMID- 29032074
TI  - Widespread Post-transcriptional Attenuation of Genomic Copy-Number Variation in
      Cancer.
AB  - Copy-number variations (CNVs) are ubiquitous in cancer and often act as driver
      events, but the effects of CNVs on the proteome of tumors are poorly understood.
      Here, we analyze recently published genomics, transcriptomics, and proteomics
      datasets made available by CPTAC and TCGA consortia on 282 breast, ovarian, and
      colorectal tumor samples to investigate the impact of CNVs in the proteomes of
      these cells. We found that CNVs are buffered by post-transcriptional regulation
      in 23%-33% of proteins that are significantly enriched in protein complex
      members. Our analyses show that complex subunits are highly co-regulated, and
      some act as rate-limiting steps of complex assembly, as their depletion induces
      decreased abundance of other complex members. We identified 48 such rate-limiting
      interactions and experimentally confirmed our predictions on the interactions of
      AP3B1 with AP3M1 and GTF2E2 with GTF2E1. This study highlights the importance of
      post-transcriptional mechanisms in cancer that allow cells to cope with their
      altered genomes.

PMID- 29032075
TI  - Synthesis, structures, and ESI-mass studies of silver(I) derivatives of
      imidazolidine-2-thiones: Antimicrobial potential and biosafety evaluation.
AB  - The basic objective of this investigation is to explore potential metallo-organic
      antimicrobial agents based on silver-heterocyclic-2-thiones. In this respect, a
      series of silver(I) halide complexes with imidazolidine-2-thiones (L-NR, R=H, Me,
      Et, Prn, Bun, Ph), namely, mononuclear [AgX(L-NR)(PPh3)2] (X, R: Cl, Bu, 1; Br,
      Ph, 7); [AgX(L-NR)3] (Br, Bu, 5; Br, Prn, 8) and halogen bridged dinuclear
      [Ag2(MU-X)2(L-NR)2(PPh3)2] (Cl, Bun, 2; Cl, Ph, 3; Cl, Prn, 4; Br, Ph, 6) have
      been synthesized and characterized using modern techniques. The thio-ligands are
      terminally S-bonded in all the complexes. The in vitro antimicrobial potential
      and biosafety evaluation of the above complexes as well as that of previously
      reported analogous silver complexes has been studied against Gram positive
      bacteria, namely, Staphylococcus aureus (MTCC 740) and Methicillin resistant
      Staphylococcus aureus (MRSA), Gram negative bacteria Klebsiella pneumoniae (MTCC
      109), Salmonella typhimurium (MTCC 98) and a yeast Candida albicans (MTCC 227).
      Most of the complexes tested have shown significant antimicrobial activity with
      low values of minimum inhibitory concentration (MIC). Significantly, the activity
      against MRSA is an important outcome of this investigation. Among complexes
      tested for their cytotoxicity using MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5
      diphenyl tetrazolium bromide] assay, some complexes showed low cellular toxicity
      with high percent cell viability. A dinuclear complex [Ag2(MU-Cl)2(L
      NPh)2(PPh3)2] 3 with 93.3% cell viability emerges the most important candidate
      for further investigations.

PMID- 29032077
TI  - Linoleic acid and risk of type 2 diabetes.

PMID- 29032080
TI  - Is the new treatment for Cushing's disease too sweet?

PMID- 29032081
TI  - Protein malnutrition after weaning disrupts peripheral clock and daily insulin
      secretion in mice.
AB  - Changes in nutritional state may alter circadian rhythms through alterations in
      expression of clock genes. Protein deficiency has a profound effect on body
      metabolism, but the effect of this nutrient restriction after weaning on
      biological clock has not been explored. Thus, this study aims to investigate
      whether the protein restriction affects the daily oscillation in the behavior and
      metabolic rhythms, as well as expression of clock genes in peripheral tissues.
      Male C57BL/6 J mice, after weaning, were fed a normal-protein (NP) diet or a low
      protein (LP) diet for 8 weeks. Mice fed an LP diet did not show difference in
      locomotor activity and energy expenditure, but the food intake was increased,
      with parallel increased expression of the orexigenic neuropeptide Npy and
      disruption of the anorexigenic Pomc oscillatory pattern in the hypothalamus. LP
      mice showed disruption in the daily rhythmic patterns of plasma glucose,
      triglycerides and insulin. Also, the rhythmic expression of clock genes in
      peripheral tissues and pancreatic islets was altered in LP mice. In pancreatic
      islets, the disruption of clock genes was followed by impairment of daily glucose
      stimulated insulin secretion and the expression of genes involved in exocytosis.
      Pharmacological activation of REV-ERBalpha could not restore the insulin
      secretion in LP mice. The present study demonstrates that protein restriction,
      leading to development of malnutrition, alters the peripheral clock and metabolic
      outputs, suggesting that this nutrient provides important entraining cues to
      regulate the daily fluctuation of biological clock.

PMID- 29032078
TI  - Efficacy and safety of once-monthly pasireotide in Cushing's disease: a 12 month
      clinical trial.
AB  - BACKGROUND: Cushing's disease is a rare debilitating endocrine disorder for which
      few prospective interventional studies have been done. We report results of the
      first phase 3 trial assessing long-acting intramuscular pasireotide in patients
      with Cushing's disease. METHODS: In this phase 3 clinical trial we recruited
      patients aged 18 years or older with persistent, recurrent, or de-novo (non
      surgical candidates) Cushing's disease who had a mean urinary free cortisol
      (mUFC) concentration (from three 24 h samples) of 1.5-5.0 times the upper limit
      of normal (ULN), a normal or greater than normal morning plasma
      adrenocorticotropic hormone concentration, and a pituitary source of Cushing's
      syndrome, from 57 sites across 19 countries. Exclusion criteria included previous
      pasireotide treatment, mitotane therapy within 6 months, and pituitary
      irradiation within 10 years. We randomly allocated patients 1:1 (block size of
      four) using an interactive-response-technology system to intramuscular
      pasireotide 10 mg or 30 mg every 4 weeks for 12 months (in the core phase). We
      stratified randomisation by screening mUFC concentration (1.5 to <2.0 * ULN and
      2.0-5.0 * ULN). The dose could be uptitrated (from 10 mg to 30 mg or from 30 mg
      to 40 mg) at month 4 if the mUFC concentration was greater than 1.5 * ULN, and at
      month 7, month 9, or month 12 if the mUFC concentration was greater than 1.0 *
      ULN. Investigators, patients, site personnel, and those assessing outcomes were
      masked to dose group allocation. The primary endpoint was the proportion of
      patients in each group with an mUFC concentration of less than or equal to the
      ULN at month 7. Efficacy analyses were based on intention to treat. This trial is
      registered with ClinicalTrials.gov, number NCT01374906. FINDINGS: Between Dec 28,
      2011, and Dec 9, 2014, we randomly allocated 150 patients to receive pasireotide
      10 mg (74 [49%] patients) or 30 mg (76 [51%] patients). The primary efficacy
      endpoint was met by 31 (41.9% [95% CI 30.5-53.9]) of 74 patients in the 10 mg
      group and 31 (40.8% [29.7-52.7]) of 76 in the 30 mg group. The most common
      adverse events were hyperglycaemia (36 [49%] in the 10 mg group and 36 [47%] in
      the 30 mg group), diarrhoea (26 [35%] and 33 [43%]), cholelithiasis (15 [20%] and
      34 [45%]), diabetes mellitus (14 [19%] and 18 [24%]), and nausea (15 [20%] and 16
      [21%]). Serious adverse events suspected to be study drug related were reported
      in eight (11%) patients in the 10 mg group and four (5%) in the 30 mg group. Two
      (3%) patients in the 30 mg group died during the study (pulmonary artery
      thrombosis and cardiorespiratory failure); neither death was judged to be related
      to the study drug. INTERPRETATION: Long-acting pasireotide normalised mUFC
      concentration in about 40% of patients with Cushing's disease at month 7 and had
      a similar safety profile to that of twice-daily subcutaneous pasireotide. Long
      acting pasireotide is an efficacious treatment option for some patients with
      Cushing's disease who have persistent or recurrent disease after initial surgery
      or are not surgical candidates, and provides a convenient monthly administration
      schedule. FUNDING: Novartis Pharma AG.

PMID- 29032083
TI  - Antimicrobial and antioxidant properties of polyvinyl alcohol bio composite films
      containing seaweed extracted cellulose nano-crystal and basil leaves extract.
AB  - Polyvinyl alcohol (PVA) films containing seaweed extracted cellulose nanocrystal
      (CNC) (5% w/v) and 5, 10, and 20% (w/v) basil leaves extract (BE) were prepared
      using the solvent casting method, and their physical properties, and
      antimicrobial and antioxidant activity were analyzed. The addition of 5% (w/v)
      CNC to PVA improved the tensile strength and water vapor permeability. Addition
      of BE to film the antioxidant activity and antimicrobial properties of the films
      were enhanced. Further, increasing the amount of BE slightly affected the color
      of the bio-nanocomposites. The thermal stability of films was improved with
      addition of CNC. Due to functional groups and linkage properties of the CNC
      surface and macromolecular chains of the PVA were responsible for improvement of
      the interfacial interactions between the CNC and PVA. The dispersion of CNC in
      PVA were affected with increase in the amount of BE in PVA. This study showed the
      benefits of the incorporation of CNC and BE into PVA films and the potential for
      their use as active packaging material for food.

PMID- 29032084
TI  - Facile synthesis of low-cost magnetic biosorbent from peach gum polysaccharide
      for selective and efficient removal of cationic dyes.
AB  - Magnetic biosorbents derived from renewable resource are emerging as a new class
      of adsorbing material for environmental cleanup because of their eco-friendly
      characteristic, easy availability and low cost. Herein, a novel magnetic peach
      gum bead (MPGB) biosorbent was successfully fabricated by a simple one-step
      reaction based on the simultaneous formation of magnetic nanoparticles and cross
      linking of natural peach gum polysaccharide. Benefiting from the combined merits
      of peach gum and magnetic nanoparticles, the MPGB not only showed excellent
      adsorption performance for cationic dyes but also exhibited convenient magnetic
      separation capability. The influences of pH, ionic strength, initial dye
      concentration, contact time and temperature on the adsorption property of MPGB
      biosorbent were investigated by choosing methylene blue (MB) as a representative
      cationic dye. The Langmuir isotherm fitted the adsorption isotherm well with
      maximum adsorption capacity of 231.5mgg-1. Kinetic data showed good correlation
      with pseudo-second-order model. Thermodynamic investigation revealed that the
      adsorption process was spontaneous and endothermic. Moreover, the MPGB exhibits
      nice reusability. Considering the facile fabrication process and excellent
      adsorption performance, the MPGBs hold great promise for using as biosorbent for
      environmental cleanup.

PMID- 29032082
TI  - Effects of triclosan on hormones and reproductive axis in female Yellow River
      carp (Cyprinus carpio): Potential mechanisms underlying estrogen effect.
AB  - Triclosan (TCS), a member of the class of compounds called pharmaceutical and
      personal care products (PPCPs), is a broad antibacterial and antifungal agent
      found in a lot of consumer products. However, TCS hormone effect mechanism in
      teleost female fish is not clear. Female Yellow River carp (Cyprinus carpio) were
      exposed to 1/20, 1/10 and 1/5 LC50 TCS (96h LC50 of TCS to carp) under semi
      static conditions for 42days. Vitellogenin (Vtg), 17beta-estradiol (E2),
      testosterone(T), estrogen receptor (Er), gonadotropin (GtH), and gonadotropin
      releasing hormone (GnRH) levels were measured by enzyme-linked immunosorbent
      assay (ELISA). Meanwhile, we also examined the mRNA expressions of aromatase,
      GtHs-beta, GnRH, and Er by quantitative real-time PCR (qRT-PCR). The results
      indicated that 1/5 LC50 TCS induced Vtg in hepatopancreas of female carps by
      interference with the hypothalamic-pituitary-gonadal (HPG) axis at multiple
      potential loci through three mechanisms: (a) TCS exposure enhanced the mRNA
      expression of hypothalamus and gonadal aromatase which converts androgens into
      estrogens, subsequently increasing serum concentrations of E2 to induce Vtg in
      hepatopancreas; (b) TCS treatment increased GnRH and GtH-beta mRNA expression and
      secretion, causing the disturbance of reproductive endocrine and the increase of
      E2 to induce Vtg in hepatopancreas; (c) TCS exposure enhanced synthesis and
      secretion of Er, then it bound to Er to active Vtg synthesis. These mechanisms
      showed that TCS may induce Vtg production in female Yellow River carp by Er
      mediated and non-Er-mediated pathways.

PMID- 29032079
TI  - Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of
      individual-level data for 39 740 adults from 20 prospective cohort studies.
AB  - BACKGROUND: The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs)
      remain contentious, and little evidence is available regarding their potential
      role in primary prevention of type 2 diabetes. We aimed to assess the
      associations of linoleic acid and arachidonic acid biomarkers with incident type
      2 diabetes. METHODS: We did a pooled analysis of new, harmonised, individual
      level analyses for the biomarkers linoleic acid and its metabolite arachidonic
      acid and incident type 2 diabetes. We analysed data from 20 prospective cohort
      studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK,
      Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between
      1970 and 2010. Participants included in the analyses were aged 18 years or older
      and had data available for linoleic acid and arachidonic acid biomarkers at
      baseline. We excluded participants with type 2 diabetes at baseline. The main
      outcome was the association between omega-6 PUFA biomarkers and incident type 2
      diabetes. We assessed the relative risk of type 2 diabetes prospectively for each
      cohort and lipid compartment separately using a prespecified analytic plan for
      exposures, covariates, effect modifiers, and analysis, and the findings were then
      pooled using inverse-variance weighted meta-analysis. FINDINGS: Participants were
      39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of
      cohort means) of 23.3-28.4 kg/m2, who did not have type 2 diabetes at baseline.
      During a follow-up of 366 073 person-years, we identified 4347 cases of incident
      type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of
      linoleic acid biomarkers as percentages of total fatty acid were associated with
      a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range
      0.65, 95% CI 0.60-0.72, p<0.0001; I2=53.9%, pheterogeneity=0.002). The
      associations between linoleic acid biomarkers and type 2 diabetes were generally
      similar in different lipid compartments, including phospholipids, plasma,
      cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were
      not significantly associated with type 2 diabetes risk overall (RR per
      interquintile range 0.96, 95% CI 0.88-1.05; p=0.38; I2=63.0%,
      pheterogeneity<0.0001). The associations between linoleic acid and arachidonic
      acid biomarkers and the risk of type 2 diabetes were not significantly modified
      by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race,
      aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all
      pheterogeneity>=0.13). INTERPRETATION: Findings suggest that linoleic acid has
      long-term benefits for the prevention of type 2 diabetes and that arachidonic
      acid is not harmful. FUNDING: Funders are shown in the appendix.

PMID- 29032085
TI  - Fabrication and characterization of tea polyphenols loaded pullulan-CMC
      electrospun nanofiber for fruit preservation.
AB  - Edible packaging films using polymer for food preservation have been developed
      for a long time. In this study, the effects of different concentrations (0.5%,
      1%, 1.5%, w/v) of tea polyphenols incorporated into pullulan
      Carboxymethylcellulose sodium (Pul-CMC) solutions on electrospun nanofiber films
      were evaluated. The fiber size distribution was characterized by scanning
      electron microscopy. The morphological features of nanofibers were modulated
      through adjusting process parameters (e.g. concentration of polymer solution,
      applied voltage and feeding rate). Increasing the applied voltage from 19 to 21kV
      and the feed rate from 0.36 to 0.6mL/h leads to a reduction in mean fiber
      diameter. Fruit packaging potential was evaluated using strawberry. The pullulan
      CMC-TP nanofibers significantly decreased weight loss and maintained the firmness
      of the strawberries, and improved the quality of the fruit during storage. The
      findings demonstrate a facile packaging route to improve food sustainability and
      reduce waste.

PMID- 29032086
TI  - Two trypsin isoforms from albacore tuna (Thunnus alalunga) liver: Purification
      and physicochemical and biochemical characterization.
AB  - Two trypsins (A and B) from the liver of albacore tuna (Thunnus alalunga) were
      purified to homogeneity using a series of column chromatographies including
      Sephacryl S-200, Sephadex G-50 and Diethylaminoethyl-cellulose. Purity was
      increased to 80.35- and 101.23-fold with approximately 3.1 and 19.2% yield for
      trypsins A and B, respectively. The molecular weights of trypsins A and B were
      estimated to be 21 and 24kDa, respectively, by SDS-PAGE and size exclusion
      chromatography. Both trypsins showed only one band on native-PAGE. Trypsins A and
      B exhibited the maximal activity at 60 degrees C and 55 degrees C, respectively,
      and had the same optimal pH at 8.5 using Nalpha-p-Tosyl-l-arginine methyl ester
      hydrochloride (TAME) as a substrate. Stabilities of both trypsins were well
      maintained at a temperature up to 50 degrees C and in the pH range of 7.0-11.0
      and were highly dependent on the presence of calcium ion. The inhibition test
      demonstrated strong inhibition by soybean trypsin inhibitor and TLCK. Activity of
      both trypsins continuously decreased with increasing NaCl concentration (0-30%).
      The N-terminal amino acid sequence of 20 residues of the two trypsin isoforms had
      homology when compared to those of other fish trypsins.

PMID- 29032087
TI  - Are we really measuring empathy? Proposal for a new measurement framework.
AB  - Empathy - currently defined as the sharing of another's affective state - has
      been the focus of much psychological and neuroscientific research in the last
      decade, much of which has been focused on ascertaining the empathic ability of
      individuals with various clinical conditions. However, most of this work tends to
      overlook the fact that empathy is the result of a complex process requiring a
      number of intermediate processing steps. It is therefore the case that describing
      an individual or group as 'lacking empathy' lacks specificity. We argue for an
      alternative measurement framework, in which we explain variance in empathic
      response in terms of individual differences in the ability to identify another's
      emotional state ('emotion identification'), and the degree to which
      identification of another's state causes a corresponding state in the self
      ('affect sharing'). We describe how existing empathy paradigms need to be
      modified in order to fit within this measurement framework, and illustrate the
      utility of this approach with reference to examples from both cognitive
      neuroscience and clinical psychology.

PMID- 29032089
TI  - Transcranial magnetic stimulation in basic and clinical neuroscience: A
      comprehensive review of fundamental principles and novel insights.
AB  - Non-invasive brain stimulation methods, such as Transcranial Magnetic Stimulation
      (TMS), are widely used worldwide to make causality-based inferences about brain
      behavior interactions. TMS-based clinical applications have been shown promising
      to treat neurological or psychiatric diseases. TMS works by inducing non
      invasively electric currents in localized cortical regions thus modulating their
      excitability levels and ongoing activity patterns depending on stimulation
      settings: frequency, number of pulses, train duration and intertrain intervals.
      Proper use of TMS in the fundamental and clinical neuroscience research requires
      a deep understanding of its operational principles, risks, potential and
      limitations. In this article we present the principles through which TMS is
      thought to operate. Readers will be provided with the bases to be able to
      understand and critically discuss TMS studies and design hypothesis driven TMS
      applications for basic and clinical neuroscience. Moreover, some recently
      identified physiological phenomena which that can dramatically influence the
      efficacy and magnitude of TMS impact and technological and methodological
      developments to guide TMS interventions that are becoming mainstream in the field
      will be also reviewed.

PMID- 29032090
TI  - Hypothalamic-pituitary-adrenal (HPA) axis functioning as predictor of
      antidepressant response-Meta-analysis.
AB  - OBJECTIVE: Although antidepressants are effective, around 50% of depressed
      patients are non-responsive. At the same time, some patients show alterations in
      the hypothalamic-pituitary-adrenal (HPA) axis. Due to interactions with central
      monoaminergic systems, these may profit less from antidepressants. METHOD: To
      determine whether non-responders and responders differed in pre-treatment HPA
      axis functioning, the Cochrane Library, EMBASE, MEDLINE, and PsycINFO were
      searched. Studies using patients with depression being treated with
      antidepressants, and including both a pre-treatment HPA and a post-treatment
      response measure were included. Standardised mean differences were calculated for
      meta-analysis. RESULTS: Thirty-nine studies were included. Non-responders and
      responders did not differ in pre-treatment corticotropin-releasing hormone or
      adrenocorticotropic hormone. Meta-regression showed non-responders had comparably
      higher pre-treatment cortisol in studies measuring cortisol non-invasively, not
      reporting sample storage, failing to control for age, and excluding patients with
      comorbidities. CONCLUSIONS: Only studies with a specific methodological profile
      seem to be able to show that the more marked depressed patients' alterations in
      the HPA axis, the less likely they are to profit from antidepressants.

PMID- 29032091
TI  - Molecular-level insights into mercury removal mechanism by pyrite.
AB  - Natural pyrite (FeS2) has been regarded as a kind of potential sorbents to
      control mercury emission from coal-fired power plants because of its low cost and
      high affinity between mercury and FeS2. Theoretical investigations based on
      density functional theory (DFT) were carried out to discern mercury adsorption,
      reaction and desorption mechanisms over pyrite surface. DFT calculation results
      indicate that Hg0 adsorption on FeS2(100) and FeS2(110) surfaces is dominated by
      physisorption and chemisorption mechanisms, respectively. Mercury atom interacts
      strongly with Fe atom on FeS2(110) surface through the atomic orbital
      hybridization and overlap. HgS is chemically adsorbed on FeS2(100) and FeS2(110)
      surfaces. Electron density difference analysis implies that the significant
      charge accumulation around sulfur atom of adsorbed HgS molecule is closely
      associated with the strong interaction between gaseous HgS and pyrite surface.
      The reaction pathway leading to the formation of gaseous HgS is a three-step
      process: Hg0->Hg(ads)->HgS(ads)->HgS. In the second step, the energy barrier of
      diatomic surface reaction between adsorbed Hg0 and S2- monomer is approximately
      17kJ/mol. The third step is an endothermic process which requires an external
      energy of about 414.60kJ/mol to desorb the formed HgS, and is the rate
      determining step.

PMID- 29032092
TI  - Three dimensional hierarchical heterostructures of g-C3N4 nanosheets/TiO2
      nanofibers: Controllable growth via gas-solid reaction and enhanced
      photocatalytic activity under visible light.
AB  - Graphitic C3N4 nanosheets were uniformly grown on electrospun TiO2 nanofibers
      with three-dimensional nanofibrous networks via a facial gas-solid reaction. The
      mass loading of g-C3N4 nanosheets could be easily controlled by adjusting the
      mass ratios of gaseous precursors (urea) to TiO2 NFs. The three-dimensional
      hierarchical heterostructures of g-C3N4 nanosheets/TiO2 nanofibers could be
      obtained with excellent distribution and high specific surface area of 121.5m2g
      1, when the mass loading of g-C3N4 was 59.8wt.%. Under visible light irradiation,
      the degradation rate constant (rhodamine B) and the H2 evolution rate of the
      heterostructures were about 4.6 and 1.6 times of pure g-C3N4, while 23 and 167.8
      times of TiO2 nanofibers, respectively. Their enhanced performance could be
      attributed to the effective charge separation and electron transfer process. Our
      work provides an attractive strategy to construct various three-dimensional
      hierarchical heterostructures of g-C3N4 nanosheets for environmental and energy
      applications.

PMID- 29032093
TI  - Formation of brominated oligomers during phenol degradation on boron-doped
      diamond electrode.
AB  - In this research, the brominated oligomers formed during phenol degradation with
      boron-doped diamond (BDD) anode had been initially studied at three different
      concentrations of bromide (1, 10 and 100mM). The results from LC/MS analysis
      indicated that, brominated monomer, dimer and trimer of phenols resulting from
      electrophilic substitution and coupling reactions were the important reaction by
      products. Specifically, the trimer by-products were generated only in bromide
      rich systems. The reaction mechanisms concerning oligomer formations were
      proposed in detail accordingly. The above results were in well accordance with
      those recorded in the degradation experiments. As a whole, bromides and chlorides
      demonstrated quite different effects toward phenol degradation, which deepened
      our understanding on the reactions involved in BDD anode cells.

PMID- 29032088
TI  - Sleep and circadian disruption and incident breast cancer risk: An evidence-based
      and theoretical review.
AB  - Opportunities for restorative sleep and optimal sleep-wake schedules are becoming
      luxuries in industrialized cultures, yet accumulating research has revealed
      multiple adverse health effects of disruptions in sleep and circadian rhythms,
      including increased risk of breast cancer. The literature on breast cancer risk
      has focused largely on adverse effects of night shift work and exposure to light
      at night (LAN), without considering potential effects of associated sleep
      disruptions. As it stands, studies on breast cancer risk have not considered the
      impact of both sleep and circadian disruption, and the possible interaction of
      the two through bidirectional pathways, on breast cancer risk in the population
      at large. We review and synthesize this literature, including: 1) studies of
      circadian disruption and incident breast cancer; 2) evidence for bidirectional
      interactions between sleep and circadian systems; 3) studies of sleep and
      incident breast cancer; and 4) potential mechanistic pathways by which
      interrelated sleep and circadian disruption may contribute to the etiology of
      breast cancer.

PMID- 29032094
TI  - Bicarbonate-activated hydrogen peroxide and efficient decontamination of toxic
      sulfur mustard and nerve gas simulants.
AB  - 13C NMR spectra showed that peroxymonocarbonate (HCO4-) was generated in the
      NaHCO3-activated H2O2 solution and pH was a key factor in its production. A cycle
      for the bicarbonate anion was proposed as HCO3-->HCO3 -> (CO2)2*->CO2(aq)->HCO4-
      (H2CO4)->HCO3- (HCO3) basing on the results of NMR, electron paramagnetic
      resonance, chemiluminescence analysis. In this cycle, (CO2)2* was the key
      intermediate and (CO2)2*->2CO2+hv was the rate controlling step. Thioanisole and
      paraoxon, the simulants of sulfur mustard gas and nerve gas, respectively, were
      efficiently decontaminated by the NaHCO3-activated H2O2 solution. While HCO4- was
      the primary oxidant for the oxidation of thioanisole, O2- generated during the
      decomposition of HCO4- or H2O2 led to the secondary oxidation of the sulfide.
      Paraoxon was degraded in the NaHCO3-activated H2O2 solution via nucleophilic
      substitution by OOH- and OH-, and the degradation rate increased exponentially
      with increasing pH. Alkali metal ions had a catalytic effect on the degradation
      of paraoxon. Mustard gas and soman degraded efficiently into nontoxic products in
      NaHCO3-activated H2O2. A pH range of 9-10 was found to be optimum for the broad
      spectrum decontamination of chemical warfare agents and other eco-toxicants using
      NaHCO3-activated H2O2.

PMID- 29032095
TI  - A review on environmental monitoring of water organic pollutants identified by EU
      guidelines.
AB  - The contamination of fresh water is a global concern. The huge impact of natural
      and anthropogenic organic substances that are constantly released into the
      environment, demands a better knowledge of the chemical status of Earth's surface
      water. Water quality monitoring studies have been performed targeting different
      substances and/or classes of substances, in different regions of the world, using
      different types of sampling strategies and campaigns. This review article aims to
      gather the available dispersed information regarding the occurrence of priority
      substances (PSs) and contaminants of emerging concern (CECs) that must be
      monitored in Europe in surface water, according to the European Union Directive
      2013/39/EU and the Watch List of Decision 2015/495/EU, respectively. Other
      specific organic pollutants not considered in these EU documents as substances of
      high concern, but with reported elevated frequency of detection at high
      concentrations, are also discussed. The search comprised worldwide publications
      from 2012, considering at least one of the following criteria: 4 sampling
      campaigns per year, wet and dry seasons, temporal and/or spatial monitoring of
      surface (river, estuarine, lake and/or coastal waters) and ground waters. The
      highest concentrations were found for: (i) the PSs atrazine, alachlor,
      trifluralin, heptachlor, hexachlorocyclohexane, polycyclic aromatic hydrocarbons
      and di(2-ethylhexyl)phthalate; (ii) the CECs azithromycin, clarithromycin,
      erythromycin, diclofenac, 17alpha-ethinylestradiol, imidacloprid and 2-ethylhexyl
      4-methoxycinnamate; and (iii) other unregulated organic compounds (caffeine,
      naproxen, metolachlor, estriol, dimethoate, terbuthylazine, acetaminophen,
      ibuprofen, trimethoprim, ciprofloxacin, ketoprofen, atenolol, Bisphenol A,
      metoprolol, carbofuran, malathion, sulfamethoxazole, carbamazepine and
      ofloxacin). Most frequent substances as well as those found at highest
      concentrations in different seasons and regions, together with available risk
      assessment data, may be useful to identify possible future PS candidates.

PMID- 29032096
TI  - Influence of inoculating white-rot fungi on organic matter transformations and
      mobility of heavy metals in sewage sludge based composting.
AB  - White-rot fungi, Phanerochaete chrysosporium was inoculated to sewage sludge
      composting. Its effect on transformation of organic matter and mobility of heavy
      metals (Zn, Pb, Cu, and Ni) was studied. Detailed sampling was performed to
      measure C contents in humic extracts (HE), humic acids (HAs), fulvic acids (FAs),
      humin and distribution of heavy metals, including acid exchangeable fraction
      (AE), reducible fraction (RED), oxidization fraction (OXI) and residual fraction
      (RES). In our study, it is evident that the HE, HAs increased obviously and
      hydrolyzed humin decreased markedly in inoculation. The stabilization rate
      ((OXI+RES)/(AE+RED)) of Zn, Pb, Cu, and Ni was 20.31%, 7%, 14.3% and 19.79%
      higher in inoculating reactor. Additionally, the changes of heavy metals
      fractions could be explained by the organic variables. The results of this study
      demonstrated that Phanerochaete chrysosporium passivates the heavy metal by
      provoking the formation of humus.

PMID- 29032098
TI  - Calcination effect of borate-bearing hydroxyapatite on the mobility of borate.
AB  - Discharge from accidental nuclear power plants includes boric acid, which is used
      as a neutron absorbent in nuclear reactors. Co-precipitation of borate with
      hydroxyapatite (HAp), using Ca(OH)2, is known to be an effectively fast method
      for stabilization of borate as well as coexisting radioactive nuclides. To reduce
      bulky volume of solid residues after co-precipitation, calcination is necessary
      to investigate the chemical stability of targets. Calcination at 850 degrees C
      resulted in the high crystalization of HAp with formation of xCaO.B2O3 as a by
      phase in which x increased with a decrease in the borate contents. After
      calcination, the lattice parameter a of HAp showed a reentrant curve and c showed
      a convex curve with an increase in borate contents. A dissolution assay revealed
      that calcination sometimes increases the borate moiety and that the acceptable B
      contents in HAp are lower than 1.59mmol/g-calcined HAp. These results imply that
      during calcination of HAp, some borate is excluded to form the by-phase
      xCaO.B2O3, which is relatively insoluble in water, but some other fractions might
      be additionally emitted from the amorphous phase to weakly bind the calcined
      products.

PMID- 29032097
TI  - Comparative assessment of the adverse outcome of wastewater effluents by
      integrating oxidative stress and histopathological alterations in endemic fish.
AB  - This study evaluated the adverse effect of wastewater effluents on three fish
      species, Carassius auratus, Zacco platypus, and Zacco koreanus, collected in the
      Eungcheon, Mihocheon, and Busocheon streams, respectively. Fish gills, liver, and
      kidneys from the mixing zone (MZ) and sites upstream (US) and downstream (DS) of
      the MZ were analyzed for oxidative stress responses and histology. Catalase and
      glutathione S-transferase activity was significantly higher at MZ and DS than
      from US (p<0.05), indicating induction of antioxidant defense mechanisms.
      Additionally, degree of tissue changes (DTC) indicated highest histopathological
      alteration in MZ, followed by DS and US. Integrated biomarker response (IBR) for
      oxidative stress and histopathological alterations showed higher values
      consistently for Z. koreanus than other two species. Water temperature, EC, and
      TN levels seemed to be responsible for the observed biomarker responses. These
      findings indicate that thermal hot spring effluent discharged into Busocheon
      steam induced the most significant impact on the cool water species (Z.
      koreanus). Overall, this study suggests that the IBR index is a very useful tool
      for monitoring in situ adverse effects of wastewater effluents on fish,
      particularly for histopathological alterations representing prolonged impact.

PMID- 29032099
TI  - Roles of hydroxyl and sulfate radicals in degradation of trichloroethene by
      persulfate activated with Fe2+ and zero-valent iron: Insights from carbon isotope
      fractionation.
AB  - Active species including hydroxyl (HO) and sulfate radicals (SO4-) play important
      roles in contaminant degradation during the persulfate based in-situ chemical
      oxidation (ISCO) process. The generation and contribution of active species are
      critical and can potentially be evaluated using compound specific isotope
      analysis (CSIA). However, the evaluation of stable isotope fractionation (or
      isotope enrichment factor epsilon values) for contaminants degraded by individual
      active species of concern is required but lacking. This study firstly determined
      the carbon isotope fractionation of trichloroethene (TCE) degradation by SO4.-
      with chemical probe methods to obtain epsilon values from -6.4+/-0.7 to -6.9+/
      0.50/00. The epsilon values were significantly different from those reported for
      TCE degradation by HO, which could be used to identify the competing TCE
      degradation by HO and SO4-. Relying on the observed epsilon values and the
      extended Rayleigh-type equation, the contributions of SO4- and HO to TCE
      degradation were evaluated in persulfate activated by Fe0 or Fe(II). This study
      provides an illuminating idea to determine stable isotope fractionation for
      contaminant degradation by individual active species, which is crucial for the
      application of CSIA in relevant environments.

PMID- 29032100
TI  - [Severity of illness index in autoimmune diseases: Have there any usefulness in
      medical practice?]
AB  - INTRODUCTION: Assessing disease activity in patients suffering from autoimmune
      diseases is complex. Symptoms are multiple, often subjective and there are no
      reliable biomarkers. Many activity scores have been implemented to compare
      treatment efficacy in clinical trials. Their use in clinical practice is largely
      unknown. We performed a practical survey to analyze the use of activity scores in
      clinical practice to consider treatment response and to assess the determinants
      of their use. METHODS: A sample of French internists answered a questionnaire
      about activity scores of systemic lupus erythematosus, Sjogren's syndrome,
      autoimmune myositis and necrotizing vasculitis of small vessels. The frequency of
      use of these tools, the causes of their non-use, and the general opinion of
      practitioners about the place of theses scores in current practice were
      described. RESULTS: The form was completed by 92 internists. Seventy percent of
      them supported the use of activity scores in consultations, but actually used
      them in less than 25% of patient visits. The reasons for the low use of these
      scores are mainly the ignorance of their existence (42%) and their length or
      complexity (28%). CONCLUSION: The discrepancy between the ratio of practitioners
      who believe that scores have a place in daily practice and their actual use shows
      that the current scores do not meet the needs. The implementation of easily
      usable activity scores in inflammatory diseases remains a challenge for the
      internists.

PMID- 29032101
TI  - Mitochondrial activity in T cells.
AB  - Mitochondria fulfill important and diverse roles during the different stages of T
      cell adaptive responses. Here we discuss the role of the mitochondria in T cells
      from the initial steps of activation at the immune synapse to their participation
      in memory response and T cell exhaustion. Mitochondria are relocated to the
      immune synapse in order to supply local ATP and to aid calcium signaling. During
      expansion and proliferation, mitochondrial reactive oxygen species drive
      proliferation. Aerobic glycolysis, glutaminolysis and fatty acid oxidation
      regulate the program of differentiation into effector or regulatory T cell
      subsets, and mitochondrial remodeling proteins are required for the long-lasting
      phenotype of memory cells.

PMID- 29032103
TI  - Mast cells in atherosclerotic cardiovascular disease - Activators and actions.
AB  - Mast cells are potent actors involved in inflammatory reactions in various
      tissues, including both in the intimal and the adventitial layers of
      atherosclerotic arteries. In the arterial intima, the site of atherogenesis, mast
      cells are activated to degranulate, and thereby triggered to release an abundance
      of preformed inflammatory mediators, notably histamine, heparin, neutral
      proteases and cytokines stored in their cytoplasmic secretory granules. Depending
      on the stimulus, mast cell activation may also launch prolonged synthesis and
      secretion of single bioactive molecules, such as cytokines and derivatives of
      arachidonic acid. The mast cell-derived mediators may impede the functions of
      different types of cells present in atherosclerotic lesions, and also compromise
      the structural and functional integrity of the intimal extracellular matrix. In
      the adventitial layer of atherosclerotic coronary arteries, mast cells locate
      next to peptidergic sensory nerve fibers, which, by releasing neuropeptides may
      activate mast cells to release vasoactive compounds capable of triggering local
      vasoconstriction. The concerted actions of arterial mast cells have the potential
      to contribute to the initiation and progression of atherosclerosis, and
      ultimately to destabilization and rupture of an advanced atherosclerotic plaque
      with ensuing atherothrombotic complications.

PMID- 29032102
TI  - Regulation of Ca2+ signaling by acute hypoxia and acidosis in rat neonatal
      cardiomyocytes.
AB  - : Ischemic heart disease is an arrhythmogenic condition, accompanied by hypoxia,
      acidosis, and impaired Ca2+ signaling. Here we report on effects of acute hypoxia
      and acidification in rat neonatal cardiomyocytes cultures. RESULTS: Two
      populations of neonatal cardiomyocyte were identified based on inactivation
      kinetics of L-type ICa: rapidly-inactivating ICa (tau~20ms) myocytes (prevalent
      in 3-4-day cultures), and slow-inactivating ICa (tau>=40ms) myocytes (dominant in
      7-day cultures). Acute hypoxia (pO2<5mmHg for 50-100s) suppressed ICa reversibly
      in both cell-types to different extent and with different kinetics. This
      disparity disappeared when Ba2+ was the channel charge carrier, or when the
      intracellular Ca2+ buffering capacity was increased by dialysis of high
      concentrations of EGTA and BAPTA, suggesting critical role for calcium-dependent
      inactivation. Suppressive effect of acute acidosis on ICa (~40%, pH6.7), on the
      other hand, was not cell-type dependent. Isoproterenol enhanced ICa in both cell
      types, but protected only against suppressive effects of acidosis and not
      hypoxia. Hypoxia and acidosis suppressed global Ca2+ transients by ~20%, but
      suppression was larger, ~35%, at the RyR2 microdomains, using GCaMP6-FKBP
      targeted probe. Hypoxia and acidosis also suppressed mitochondrial Ca2+ uptake by
      40% and 10%, respectively, using mitochondrial targeted Ca2+ biosensor (mito
      GCaMP6). CONCLUSION: Our studies suggest that acute hypoxia suppresses ICa in
      rapidly inactivating cell population by a mechanism involving Ca2+-dependent
      inactivation, while compromised mitochondrial Ca2+ uptake seems also to
      contribute to ICa suppression in slowly inactivating cell population. Proximity
      of cellular Ca2+ pools to sarcolemmal Ca2+ channels may contribute to the
      variability of inactivation kinetics of ICa in the two cell populations, while
      acidosis suppression of ICa appears mediated by proton-induced block of the
      calcium channel.

PMID- 29032104
TI  - Participation of GABAB receptors in cortical postictal excitability in immature
      rats.
AB  - Arrest of seizures is due to an active inhibition and is followed in mature brain
      by period of refractoriness markedly present one min after the end of seizures.
      To study changes in cortical excitability after epileptic seizures we used
      electrical stimulation of sensorimotor cortical area in immature rats - 25-day
      old ones with mature postictal refractoriness and 12-day-old where postictal
      potentiation of afterdischarges (ADs) is present instead of refractoriness at one
      minute after the end of the conditioning AD. GABAB receptor antagonist CGP35348
      was found to partly suppress postictal refractoriness. In present study not only
      an antagonist CGP46381 (3 and 10mg/kg i.p.) but also positive allosteric
      modulator of GABAB receptors CGP7930 (20 and 40mg/kg i.p.) were used to study the
      role of GABAB receptors in both age groups. They were injected immediately after
      testing AD and 10min later the two stimulations were repeated. CGP46381 partly
      antagonized postictal refractoriness in 25-day-old rats but did not significantly
      affect ADs in 12-day-old animals. CGP7930 did not significantly change ADs
      duration in either age group. GABAB receptors participate in mechanism of
      postictal refractoriness but did not play an important role in 12-day-old rats
      where potentiation instead of refractoriness is present.

PMID- 29032105
TI  - A comprehensive review on the anti-cancer properties and mechanisms of action of
      sesamin, a lignan in sesame seeds (Sesamum indicum).
AB  - Sesamin is the major active ingredient is Sesamum indicum seeds. Several studies
      revealed that sesamin possesses potent anti-cancer properties. The anti-cancer
      effects of sesamin have been mainly attributed to its anti-proliferative, pro
      apoptotic, anti-inflammatory, anti-metastatic, anti- and pro-angiogenic, and pro
      autophagocytic activities. In this review, we provide a comprehensive summary of
      the reported anti-cancer effects of sesamin, both in vitro and in vivo.
      Experimental findings related to the potential of sesamin to attenuate oxidative
      stress, inflammation, proliferation, metastasis, and angiogenesis in various
      cancer cells and tumors are analyzed. Studies focusing on the ability of sesamin
      to induce apoptosis and autophagy in cancer cells are also underscored. Moreover,
      the molecular mechanisms underlying the anti-cancer effects of sesamin are
      highlighted, and the major signaling pathways targeted by sesamin are identified.
      Although the exact signaling events triggered by sesamin in cancer cells are not
      fully revealed, our analysis indicates that NF-kappaB, STAT3, JNK, ERK1/2, p38
      MAPK, PI3K/AKT, caspase-3, and p53 signaling pathways are critically involved in
      mediating the anti-cancer effects of sesamin. In sum, the experimental evidence
      suggesting that sesamin could exert potent anti-cancer activities in vitro and in
      vivo is compelling. Hence, sesamin can potentially be employed as an effective
      adjuvant therapeutic agent in ameliorating tumor development and progression, and
      therefore, it could be used in the prevention and/or treatment of various types
      of cancer.

PMID- 29032106
TI  - Effect of monoamine oxidase inhibitors on ischaemia/reperfusion-induced acute
      kidney injury in rats.
AB  - Increases in renal sympathetic nerve activity during ischaemia and renal venous
      norepinephrine levels after reperfusion play important roles in the development
      of ischaemia/reperfusion-induced acute kidney injury. In the present study, we
      examined the effect of isatin, an endogenous monoamine oxidase inhibitor, on
      renal venous norepinephrine levels, superoxide production after reperfusion, and
      ischaemia/reperfusion-induced acute kidney injury. Ischaemia/reperfusion-induced
      acute kidney injury was accomplished by clamping the left renal artery and vein
      for 45min, followed by reperfusion, 2 weeks after contralateral nephrectomy.
      Renal superoxide production and norepinephrine overflow were elevated and
      significant renal tissue damage was observed following ischaemia/reperfusion
      injury. Intravenous injection of isatin (10mg/kg) at 5min before ischaemia
      increased the renal venous plasma norepinephrine level after reperfusion and
      aggravated ischaemia/reperfusion-induced renal dysfunction and histological
      damage. The excessive superoxide production after reperfusion was significantly
      suppressed by isatin administration, indicating that the inhibition of oxidative
      deamination effectively suppressed superoxide production. These data suggest that
      the exacerbation effect of isatin is associated, at least in part, with increased
      norepinephrine levels but not with superoxide production. To the best of our
      knowledge, this is the first report of isatin involvement in the pathogenesis
      and/or development of acute kidney injury.

PMID- 29032107
TI  - Long-term Outcomes of Ocular Surface Stem Cell Allograft Transplantation.
AB  - PURPOSE: To investigate the long-term outcomes of ocular surface stem cell
      allograft transplantation (OSST) in patients with total limbal stem cell
      deficiency (LSCD) owing to various etiologies with a follow-up >= 5 years.
      DESIGN: Retrospective interventional cohort. METHODS: Setting: Single tertiary
      referral hospital. STUDY POPULATION: Patients who had (1) presence of total LSCD,
      (2) surgical treatment with at least 1 allograft OSST procedure, and (3) minimum
      follow-up >= 5 years after OSST. INTERVENTION: All patients underwent allograft
      OSST from March 1998 to June 2009. All patients received systemic
      immunosuppression. MAIN OUTCOME MEASURES: Ocular surface stability, best
      corrected visual acuity (BCVA). RESULTS: A total of 165 eyes of 110 patients
      fulfilled the inclusion criteria with a mean follow-up period of 109.22 +/- 35.7
      months or approximately 9.1 years (range 5.2-17.7 years). Ocular surface
      stability was achieved in 72.7% (120/165) of eyes at last follow-up, while 15.2%
      (25/165) maintained an improved ocular surface and 12.1% (20/165) developed total
      surface failure. Additional OSST surgery was necessary in 30.9% (51/165 eyes) to
      maintain a stable ocular surface. There was >= 2 lines BCVA improvement in 62.1%,
      no change in 7.7%, and a worsened BCVA in 18.6% at last follow-up. CONCLUSIONS:
      With proper immunosuppression and repeat procedure in case of failure, allograft
      OSST can provide true long-term ocular surface stability and successful visual
      outcomes.

PMID- 29032108
TI  - Pregnancy-induced Changes in Corneal Biomechanics and Topography Are Thyroid
      Hormone Related.
AB  - PURPOSE: To identify biomechanical and topographic changes of the cornea during
      pregnancy and the postpartum period and its association to hormonal changes.
      DESIGN: Prospective single-center observational cohort study. METHODS:
      Participants were 24 pregnant women (48 eyes), monitored throughout pregnancy and
      after delivery. Biomechanical and topographic corneal properties were measured
      using the Ocular Response Analyzer (ORA) and a Scheimpflug imaging system
      (Pentacam HR) each trimester and 1 month after delivery. At the same
      consultations blood plasma levels of estradiol (E2) and thyroid hormones (TSH,
      T3t, T4t) were also determined. A factorial MANCOVA was used to detect
      interactions between hormonal plasma levels and ocular parameters. RESULTS:
      Significant differences in corneal biomechanical and topographic parameters were
      found during pregnancy in relation to T3t (p = .01), T4t (p < .001), T3t/T4t (P =
      .001), and TSH (p = .001) plasma levels. E2 plasma levels (p = .092) and time
      period of measurement (p = .975) did not significantly affect corneal parameters.
      TSH levels significantly affected the maximal keratometry reading (p = .036), the
      vertical keratometry reading (p = .04), and the index of height asymmetry (p =
      .014). Those results persist after excluding hypothyroidism patients from the
      statistical analysis. CONCLUSIONS: Hormonal changes affecting corneal
      biomechanics and topography during pregnancy could be thyroid related.
      Dysthyroidism may directly influence corneal biomechanics and represents a
      clinically relevant factor that needs further investigation.

PMID- 29032109
TI  - Early Response to Intravitreal Dexamethasone Implant Therapy in Diabetic Macular
      Edema May Predict Visual Outcome.
AB  - PURPOSE: To determine whether early visual acuity response to intravitreal
      dexamethasone implant therapy in diabetic macular edema (DME) is associated with
      long-term outcome. DESIGN: Retrospective case series. METHODS: Multicenter (8
      sites) retrospective review of medical records of eyes with DME treated with 0.7
      mg intravitreal dexamethasone implant and minimum 18-month follow-up. One hundred
      and two eyes were included. Eyes with vitreoretinal interface abnormalities or
      that had undergone vitrectomy were excluded. Eyes were categorized into 3 groups
      based on change in best-corrected visual acuity (BCVA) at 3 months (logMAR
      equivalence of <5-letter, 5-9-letter, or >=10-letter gain). Visual acuity
      outcomes were determined for each early response group. The relationship between
      early (3-month) and overall change in BCVA was assessed using regression
      analysis. RESULTS: In the study population (102 eyes), <5-letter, 5- to 9-letter,
      and >=10-letter BCVA improvements were seen in 44.1%, 18.6%, and 37.3% of eyes,
      respectively, at 3 months. Among suboptimal (<5-letter) responders at 3 months,
      6.7% showed >=10-letter gains at study conclusion compared to 29% in the robust
      (>=10-letter) early response group (P = .009). Change in BCVA at 3 months showed
      significant positive correlation with overall change in BCVA (coefficient = 0.44,
      P = .002). CONCLUSIONS: A similar proportion of eyes demonstrated suboptimal (<5
      letter) and robust (>=10-letter) early response to treatment at 3 months. Eyes
      with a robust early response demonstrated >=10-letter long-term gain in BCVA at a
      significantly higher rate compared to those with poor early response. Early
      treatment response directly correlated with overall change in BCVA.

PMID- 29032110
TI  - Use of Donors Predisposed by Corneal Collagen Cross-linking in Penetrating
      Keratoplasty for Treating Patients With Keratoconus.
AB  - PURPOSE: To investigate whether use of donors predisposed by corneal collagen
      cross-linking (CXL) reduced myopic refractive errors for keratoconic eyes after
      penetrating keratoplasty (PK). DESIGN: Randomized controlled trial. METHODS: One
      hundred sixteen eyes of 116 patients with keratoconus from Zhongshan Ophthalmic
      Center were enrolled. Using stratified block randomization, we assigned eligible
      eyes to the CXL graft group (Group 1) or conventional graft group (Group 2).
      Uncorrected distance visual acuity (UDVA), corrected distance visual acuity
      (CDVA), spherical equivalent (SE), and topographic data were compared 12, 24, and
      36 months after surgery. RESULTS: Group 1 had better UDVA and CDVA than Group 2
      after 1 year follow-up. Also, Group 1 had a lesser degree of SE and lower
      manifest cylinder than Group 2. At 3 years follow-up, mean CDVA was 0.17 +/- 0.10
      logarithm of the minimum angle of resolution (logMAR) in Group 1 vs 0.23 +/- 0.12
      logMAR in Group 2 (P = .004). Mean SE was -3.50 +/- 2.93 diopter (D) in Group 1
      and -4.02 +/- 2.57 D in Group 2 (P = .034). Mean manifest cylinder was -5.22 +/-
      2.64 D and -6.35 +/- 2.80 D in Group 1 and Group 2, respectively (P = .013). At 3
      years follow-up, simulated keratometry in the steepest meridian (Kmax) was 46.85
      +/- 2.85 D vs 49.37 +/- 2.92 D (P = .036); corneal power was 44.41 +/- 2.89 D vs
      46.35 +/- 2.87 D (P = .001); and keratometric astigmatism was 4.53 +/- 1.06 D vs
      5.98 +/- 1.28 D (P < .001) in Group 1 and Group 2, respectively. CONCLUSIONS: Use
      of donors predisposed by CXL could reduce topographic readings after PK for the
      treatment of keratoconus, and consequently reduce myopic refractive errors and
      improve visual acuity.

PMID- 29032111
TI  - Paranormal belief and errors of probabilistic reasoning: The role of constituent
      conditional relatedness in believers' susceptibility to the conjunction fallacy.
AB  - The present study examines the extent to which stronger belief in either
      extrasensory perception, psychokinesis or life-after-death is associated with a
      proneness to making conjunction errors (CEs). One hundred and sixty members of
      the UK public read eight hypothetical scenarios and for each estimated the
      likelihood that two constituent events alone plus their conjunction would occur.
      The impact of paranormal belief plus constituents' conditional relatedness type,
      estimates of the subjectively less likely and more likely constituents plus
      relevant interaction terms tested via three Generalized Linear Mixed Models.
      General qualification levels were controlled for. As expected, stronger PK
      beliefs and depiction of a positively conditionally related (verses conditionally
      unrelated) constituent pairs predicted higher CE generation. ESP and LAD beliefs
      had no impact with, surprisingly, higher estimates of the less likely constituent
      predicting fewer - not more - CEs. Theoretical implications, methodological
      issues and ideas for future research are discussed.

PMID- 29032113
TI  - Accelerating with the brakes on?

PMID- 29032112
TI  - Dermal pharmacokinetics of pyrazinamide determined by microdialysis sampling in
      rats.
AB  - Studies have demonstrated the efficacy of pyrazinamide (PZA) against stages of
      the Leishmania parasite that causes cutaneous leishmaniasis. Although PZA is
      widely distributed in most body fluids and tissues, the amount of drug reaching
      the skin is unknown. This study aimed to investigate the pharmacokinetics of PZA
      in rat dermal tissue by dermal microdialysis. Skin pharmacokinetics was assessed
      by implanting a linear microdialysis probe in the dermis of ten rats. In
      addition, blood samples were collected to assess plasma pharmacokinetics. Unbound
      microdialysate (N = 280) and plasma (N = 120) concentrations following single
      intravenous doses of 25 mg/kg or 50 mg/kg PZA were quantified by a validated HPLC
      method. Probe calibration was performed by retrodialysis. Non-compartmental
      analysis and non-linear mixed-effects modelling were performed using WinNonlin
      and NONMEM v.7.3. PZA rapidly permeated into the dermis and reached high levels,
      with mean maximum concentrations (Cmax) of 22.4 +/- 7.1 ug/mL and 48.6 +/- 17.3
      ug/mL for the two doses studied. PZA showed significant distribution to the skin
      (fAUCdermal/fAUCplasma = 0.82 +/- 0.31 and 0.84 +/- 0.25 for 25 mg/kg and 50
      mg/kg doses, respectively). Active unbound concentrations in dermal tissue
      reached lower levels than free plasma concentrations, indicating that free PZA
      levels in plasma were in equilibrium with tissue levels. These results showed
      equivalent unbound drug tissue concentrations and corresponding unbound plasma
      levels. This study shows that PZA distributes rapidly into dermal interstitial
      fluid space in rats and therefore may be a potential agent in the treatment of
      cutaneous leishmaniasis.

PMID- 29032114
TI  - Epigallocatechin-3-gallate reduces the proliferation of benign prostatic
      hyperplasia cells via regulation of focal adhesions.
AB  - AIMS: Benign prostatic hyperplasia (BPH) is the most common urological disease
      that is characterized by the excessive growth of prostatic epithelial and stromal
      cells. Pharmacological therapy for BPH has limited use due to the many side
      effects so there is a need for new agents including natural compounds such as
      epigallocatechin-3-gallate (EGCG). This study was undertaken to assess the role
      of EGCG, suppressing the formation of BPH by reducing inflammation and oxidative
      stress, in cytoskeleton organization and ECM interactions via focal adhesions.
      MAIN METHODS: We performed MTT assay to investigate cell viability of BPH-1
      cells, wound healing assay to examine cell migration, immunofluorescence assay
      for F-actin organization and paxillin distribution and finally immunoblotting to
      investigate focal adhesion protein levels in the presence and absence of EGCG.
      KEY FINDINGS: We found that EGCG inhibits cell proliferation at the concentration
      of 89.12MUM, 21.2MUM and 2.39MUM for 24, 48 and 72h, respectively as well as
      inhibitory effects of EGCG on BPH-1 cell migration were observed in a wound
      healing assay. Furthermore, it was determined by immunofluorescence labeling that
      EGCG disrupts F-actin organization and reduces paxillin distribution.
      Additionally, EGCG decreases the activation of FAK (Focal Adhesion Kinase) and
      the levels of paxillin, RhoA (Ras homolog gene family, member A), Cdc42 (cell
      division cycle 42) and PAK1 (p21 protein-activated kinase 1) in a dose-dependent
      manner. SIGNIFICANCE: For the first time, by this study, we found evidence that
      BPH-1 cell proliferation could be inhibited with EGCG through the disruption of
      cytoskeleton organization and ECM interactions. Consequently, EGCG might be
      useful in the prevention and treatment of diseases characterized by excessive
      cell proliferation such as BPH.

PMID- 29032115
TI  - Toll-like receptor 4 (TLR4) impairs nitric oxide contributing to Angiotensin II
      induced cavernosal dysfunction.
AB  - AIM: Angiotensin II (AngII), a corpus cavernosum (CC) constrictor peptide,
      modulates Toll like receptor (TLR) expression, a key element of the innate immune
      system, contributing to impaired vascular function in pathological conditions.
      However, it is unknown whether TLR4 is involved in AngII-induced erectile
      dysfunction. In this study, we investigated whether TLR4 plays a role in
      cavernosal dysfunction caused by AngII upregulation. MATERIAL AND METHODS:
      Cavernosal smooth muscle cells (CSMC) from C57/BL6 mice were treated with AngII
      (0.1MUM) or bacterial LPS (50ng/ml) for 12-24h and TLR4 expression was assessed.
      Mice were infused with AngII (90ng/min, 28days) and treated with anti-TLR4
      antibody (0.1mg/daily, i.p.) for the last 14days of the treatment. CC tissue was
      used for functional studies and for Western blotting. Nitric Oxide Synthase (NOS)
      activity was measured by conversion of [3H]-l-arginine to [3H]-l-citrulline,
      systemic TNF-alpha levels by ELISA, and reactive oxygen species (ROS) by
      immunofluorescence. KEY FINDINGS: We report upregulation of TLR4 in CSMC
      following AngII or LPS stimulation. In AngII-infused mice, chronic treatment with
      anti-TLR4 antibody (28+/-2.1%) attenuates adrenergic CC contraction, which also
      ameliorates nitrergic (68.90+/-0.21 vs. 51.07+/-0.63, 8Hz, AngII-infused mice
      treated vs. non-treated). Decreased endothelial NOS expression, reduced NOS
      activity, and augmented levels of TNF-alpha, and ROS were found following AngII
      infusion. These alterations were prevented, or at least decreased by anti-TLR4
      antibody treatment. SIGNIFICANCE: Inhibition of TLR4 ameliorates AngII-impaired
      cavernosal relaxation, decreases TNF-alpha levels, and restores NO
      bioavailability, demonstrating that TLR4 partly mediates AngII-induced cavernosal
      dysfunction.

PMID- 29032116
TI  - Mechanisms of action for alpha1-adrenoceptor blockers in storage symptoms with
      new insights into the micturition reflex.
AB  - Elderly patients suffering from lower urinary tract symptoms with benign
      prostatic hyperplasia (BPH) are widely prescribed alpha1-adrenoceptor blockers
      (alpha1-blockers) to improve voiding and storage symptoms. The mechanism of
      action for improvements in voiding symptoms is well understood; tonus of the
      urethra and prostate are decreased and urinary flow rate is increased by alpha1
      blockers. However, the mechanisms underlying storage symptoms have remained
      unclear, although detrusor hyperactivity has been identified as a significant
      factor. Previous investigations have yielded informative results, such as
      amelioration of reduced blood flow and afferent C-fiber activation, and the
      importance of the urothelium. Recently, the fascinating role of alpha1A- and
      alpha1D-adrenoceptor subtypes have been investigated for bladder function.
      Furthermore, the scope of this pathology covers both the bladder and that part of
      the central nervous system related to the micturition reflex. This review
      describes the beneficial effects of alpha1-blockers on storage symptoms and the
      pathogenesis of storage symptoms related to BPH, discusses the mechanisms of
      action for alpha1-blockers with reference to results from cystometry to suggest
      improvements in management that suppress detrusor hyperactivity, and examines the
      potential influence of alpha1A- and alpha1D-adrenoceptor subtypes on bladder
      activity.

PMID- 29032118
TI  - The Emboldened Medical Student:Ethical Dilemmas in a University Clinic.

PMID- 29032117
TI  - Protective effects of Salvia miltiorrhiza on adenine-induced chronic renal
      failure by regulating the metabolic profiling and modulating the NADPH
      oxidase/ROS/ERK and TGF-beta/Smad signaling pathways.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Chronic renal failure (CRF) is defined as a
      progressive and irreversible loss of renal function and associated with
      inflammation and oxidative stress. Salvia miltiorrhiza (SM) is an important
      Chinese herb used in traditional Chinese medicine for treating cardiovascular
      diseases. The previous studies showed the SM exhibited significant protective
      effects on CRF. In this present study, the metabolic profiling changes and action
      mechanism of SM on CRF were explored. AIMS OF THE STUDY: The aims of this study
      were to illustrate the metabolic profiling changes of adenine induced CRF and
      analyze the protective effects and action mechanisms of SM ethanol extract (SMEE)
      and water extract (SMWE). MATERIALS AND METHODS: The animals were divided into
      normal group, CRF model group, Huangkui capsule-treated group, SMEE-treated group
      and SMWE-treated group. The UPLC-QTOFMS coupled with multivariate statistical
      methods were used to explore the changes of metabolic profile in plasma, urine
      and renal tissue from CRF rats simultaneously after treatment with SMEE and SMWE.
      Hematoxylin eosin (HE) staining and Masson staining were applied to observe
      pathological changes in renal tissue. Biochemical indicators including serum urea
      nitrogen (BUN), urine protein (UP) and serum creatinine (Scr) were measured
      according to the manufacturer's instructions of kits. Furthermore, HK-2 cell
      damaged model induced by ISF was established to access the protective effects and
      action mechanism. The dichlorodihydrofluorescein diacetate (DCFH-DA) assay was
      used to determine the reactive oxygen species (ROS) and Western blot was applied
      to analyze the expression of pathogenesis-related proteins in different groups.
      RESULTS: The results showed that the ethanol extract (SMEE) and water extract
      (SMWE) of SM significantly inhibited the elevation of serum creatinine (Scr),
      blood urea nitrogen (BUN), urine protein (UP) and indoxyl sulfate (ISF) in
      adenine-induced CRF rats, especially SMEE exhibited more significant effects.
      Moreover, SM extracts obviously improved the symptoms of glomerular and tubular
      atrophy, focal calcium deposits, interstitial fibrosis, interstitial
      inflammation, and renal tissues. By metabolomics analysis, fifty-nine metabolites
      (thirteen in plasma, twenty-seven in urine and nineteen in kidney tissue) were up
      regulated or down-regulated and contributed to CRF progress. After treatment of
      SM extracts, the altered metabolites were restored back to normal level. These
      potential biomarkers underpinning the metabolic pathways are including
      phenylalanine metabolism, pyrimidine metabolism, purine metabolism and tryptophan
      metabolism. Furthermore, SM extracts prevent epithelial-mesenchymal transition
      (EMT) of human renal tubular epithelial (HK-2) cell by inhibiting NADPH
      oxidase/ROS/ERK and TGF-beta/Smad signaling pathways. CONCLUSIONS: SMEE and SMWE
      can significantly alleviate adenine-induced CRF via regulation of the metabolic
      profiling and modulation of NADPH oxidase/ROS/ERK and TGF-beta/Smad signaling
      pathways, which provided important supports for the development of protective
      agent of SM for CRF.

PMID- 29032119
TI  - A systematic review of the safety and efficacy of systemic corticosteroids in
      atopic dermatitis.
AB  - BACKGROUND: Systemic corticosteroids are often used to treat atopic dermatitis
      (AD). However, few studies have assessed the safety and efficacy of systemic
      corticosteroids in AD. OBJECTIVE: To systematically review the literature on
      efficacy and safety of systemic corticosteroid use (oral, intramuscular, and
      intravenous) in AD. METHODS: PubMed, Embase, Medline, Scopus, Web of Science, and
      Cochrane Library were searched. We included systematic reviews, guidelines, and
      treatment reviews of systemic corticosteroid use among patients of all ages with
      a diagnosis of AD (52 reviews and 12 studies). RESULTS: There was general
      consensus in the literature to limit the use of systemic steroids to short
      courses as a bridge to steroid-sparing therapies. Systemic side effects include
      growth suppression in children, osteoporosis, osteonecrosis, adrenal
      insufficiency, Cushing syndrome, hypertension, glucose intolerance, diabetes,
      gastritis, gastroesophageal reflux, peptic ulcer disease, weight gain, emotional
      lability, behavioral changes, opportunistic infections, cataracts, glaucoma,
      myopathy, myalgia, dysaesthesia, pseudotumor cerebri, hyperlipidemia, malignancy,
      thrombosis, skin atrophy, sleep disturbance, and rebound flaring. LIMITATIONS:
      Baseline clinical severity, corticosteroid delivery and dose, and treatment
      response were reported incompletely and heterogeneously across studies.
      CONCLUSIONS: Evidence is not strong enough to determine optimal delivery or
      duration of systemic corticosteroids in AD.

PMID- 29032120
TI  - The ethical conundrum of supervising physician assistants at a distant site.

PMID- 29032121
TI  - "Arrow" mark for orientation in paramedian forehead flap.

PMID- 29032122
TI  - RIFM fragrance ingredient safety assessment, cis-3-octen-1-ol, CAS Registry
      Number 20125-84-2.

PMID- 29032123
TI  - RIFM fragrance ingredient safety assessment, 3-hexen-1-ol (isomer unspecified),
      CAS Registry Number 544-12-7.

PMID- 29032124
TI  - RIFM fragrance ingredient safety assessment, 2,2,5-trimethyl-5
      pentylcyclopentanone, CAS Registry Number 65443-14-3.

PMID- 29032125
TI  - RIFM fragrance ingredient safety assessment, tetrahydro-4-methyl-2-(2
      methylpropen-1-yl)pyran, CAS Registry Number 16409-43-1.

PMID- 29032127
TI  - Associations between Posture, Voice, and Dysphonia: A Systematic Review.
AB  - OBJECTIVE: The study aimed to systematize the associations between posture,
      voice, and dysphonia in order to support future research directions and possible
      clinical interventions. STUDY DESIGN: The study is a systematic review. METHODS:
      According to the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses flowchart, a search on PubMed/Medline, SciELO, RCAAP, LILACS, Cochrane
      Library, PEDro, and Isi Web of Knowledge was performed from their inception
      through January of 2017 using the key words "posture" and ("voice" or
      "dysphonia"). The inclusion criteria were full-text journal articles in French,
      English, Portuguese, or Spanish, exploring the relationship between posture and
      voice or dysphonia, in adult human beings. The exclusion criteria coupled
      treatments for voice disorders, literature reviews and meta-analyses, case
      studies, opinion articles, and studies linking breathing with posture without
      assessing voice. Studies were analyzed using a modified version of the Newcastle
      Ottawa Scale (NOS). RESULTS: Twelve papers met the inclusion criteria with high
      methodological quality through the NOS. The review shows that a correct posture
      is necessary for an efficient voice production; however, the relation between
      dysphonia and posture seems to be contradictory. CONCLUSION: An effective posture
      allows a subject in a static posture or while moving to more easily shift the
      tension between muscles, allowing for a free movement of the larynx without
      blockages and with benefits to voice production.

PMID- 29032128
TI  - Effectiveness of the Teacher's Vocal Health Program (TVHP) in the Municipal
      Education Network of Campo Grande, MS.
AB  - OBJECTIVE: This study aimed to implement and evaluate the effectiveness of the
      Teacher's Vocal Health Program in the Municipal Education Network in Campo
      Grande, MS, in the 2016 school year so as to reduce or extinguish the high
      prevalence of vocal symptoms among teachers. METHODS: This is an experimental
      research with convenience sampling of 48 teachers presenting with vocal symptoms.
      The Vocal Symptoms Scale was used to collect data, which according to the
      criteria of the Scientific Advisory Committee of the Medical Outcomes Trust,
      present proved psychometric properties and is specific to evaluate individuals
      with vocal alterations. The proposed Vocal Program is considered as a brief
      intervention one (3 months) and consists of qualification or instruction, as well
      as application of 5 daily vocal techniques and is controlled through individual
      monitoring spreadsheets. RESULTS: The total score average had statistically
      significant reduction in the experimental group when compared with the control
      group, which represents a positive effect concerning the program adhesion. The
      fact that there was no nullity in the subscales (limitations, physical,
      emotional) means that even submitted to the intervention, the teachers still
      present with vocal symptoms. CONCLUSION: Teacher's Vocal Health Program
      represents an effective Vocal Health Program model for the teachers.

PMID- 29032126
TI  - Weekly follow up of acute lesions in three early multiple sclerosis patients
      using MR spectroscopy and diffusion.
AB  - OBJECT: Pathophysiological mechanisms underlying multiple sclerosis (MS) lesion
      formation, including inflammation, demyelination/remyelination and axonal damage,
      and their temporal evolution are still not clearly understood. To this end, three
      acute white matter lesions were monitored using a weekly multimodal magnetic
      resonance (MR) protocol. MATERIALS AND METHODS: Three untreated patients with
      early relapsing-remitting MS and one healthy control subject were followed weekly
      for two months. MR protocol included conventional MR imaging (MRI), diffusion
      tensor imaging (DTI), and localized MR spectroscopy (MRS), performed on the
      largest gadolinium-enhancing lesion, selected at the first exam. RESULTS: Mean
      diffusivity increased and fractional anisotropy decreased in lesions compared to
      healthy control. Cho/Cr ratios remained elevated in lesions throughout the follow
      up. In contrast, temporal profiles of mI/Cr ratios varied between patients'
      lesions. For patient 1, mI/Cr ratios were already elevated at the beginning of
      the follow-up. Patients 2 and 3 ratios increase was delayed by two and five
      weeks. Blood-brain barrier (BBB) recovery occurred after three weeks. CONCLUSION:
      This multimodal MR follow-up highlighted the complementary role of DTI and MRS in
      identifying temporal relationships between BBB disruption, inflammation, and
      demyelination. Diffusion metrics showed high sensitivity to detect inflammatory
      processes. The different temporal profiles of mI suggested a potential better
      specificity to monitor pathological mechanisms occurring after lesion formation,
      such as glial proliferation and remyelination.

PMID- 29032129
TI  - Linear Measurements of Vocal Folds and Laryngeal Dimensions in Freshly Excised
      Human Larynges.
AB  - INTRODUCTION: Understanding the morphology of the larynx, one of the most complex
      organs of the human body, is an important step toward understanding the detailed
      laryngeal anatomy, and physiology. Different studies have described the linear
      measurements of the larynx in different measuring methods, but no studies have
      been structured to describe vocal fold length in freshly excised larynges.
      OBJECTIVES: The aim of this study was to describe exact anatomical measurements
      of vocal folds and some laryngeal structures in freshly excised larynges, and to
      compare such measurements between males and females. This can help improve the
      diagnostic and therapeutic procedures in the laryngology field. SUBJECTS AND
      METHODS: This study was applied on 21 patients having different types of
      laryngeal carcinoma: 11 males and 10 females with the age range 41-75 years old.
      Every patient was assessed using laryngeal endoscopy and photography, and the
      length of the membranous vocal fold was measured using a millimeter-graded ruler
      that was photographed with focus with the same magnification used in the video
      laryngoscopy of the glottis. Then patients were exposed to total laryngectomy,
      and excised larynges were used for a direct measuring of the membranous and
      cartilaginous vocal folds. Then measures of men and women were compared
      statistically. Measures of excised larynges were also compared with those of the
      video endoscopy using a video-printed ruler. CONCLUSION: Freshly excised larynges
      can be used for accurate quantitative measuring of the vocal fold length and
      laryngeal dimensions. There are considerable differences in all measured
      dimensions between males and females.

PMID- 29032130
TI  - Nonmedical Treatments of Vocal Fold Nodules: A Systematic Review.
AB  - OBJECTIVES: The aim of the present systematic review was to investigate the
      nonmedical treatments of vocal fold nodules (VFNs). STUDY DESIGN: The present
      study is a systematic review. METHODS: The following electronic databases were
      searched from inception until August 2016: PubMed, Scopus, ScienceDirect, Ovid,
      ISI (Web of Sciences), Cochrane, PsychINFO, The Cochrane Central Register of
      Controlled Trials, and Google Scholar. Reference lists of included articles were
      evaluated for additional data. Preferred Reporting Items for Systematic Review
      and Meta-Analysis guidelines were used to carry out and report the review. The
      methodological quality of the articles included was evaluated using the
      Physiotherapy Evidence Database scale. Due to the heterogeneity of the studies, a
      narrative synthesis of the evidence was performed to summarize the evidence.
      RESULTS: Out of 2,099 records identified, 21 articles met the inclusion criteria
      and thus were included in the review. The studies investigated in the present
      review were different in terms of study design, participant characteristics,
      types of assessments and treatments, and treatment delivery. However, nonmedical
      treatments of VFNs were found to be successful in improving vocal quality,
      decreasing VFN sizes, and resolving these nodules. CONCLUSIONS: The results of
      the present review could provide primary evidence related to the effectiveness of
      nonmedical treatment of VFNs. Yet further studies with a high level of evidence,
      a rigorous methodological quality, and long-term follow-up evaluations are
      required to make stronger claims.

PMID- 29032131
TI  - Association Between Type 2 Diabetes and All-Cause Hospitalization and Mortality
      in the UK General Heart Failure Population: Stratification by Diabetic Glycemic
      Control and Medication Intensification.
AB  - OBJECTIVES: This study sought to investigate in the general heart failure (HF)
      population, whether the associations between type 2 diabetes (T2D) and risk of
      hospitalization and death, are modified by changing glycemic or drug treatment
      intensity. BACKGROUND: In the general HF population, T2D confers a higher risk of
      poor outcomes, but whether this risk is modified by the diabetes status is
      unknown. METHODS: A nested case-control study in an incident HF database cohort
      (2002 to 2014) compared patients with T2D with those without for risk of all
      cause first hospitalization and death. T2D was stratified by categories of
      glycosylated hemoglobin (HbA1c) or drug treatments measured 6 months before
      hospitalization and 1 year before death and compared with the HF group without
      T2D. RESULTS: In HF, T2D was associated with risk of first hospitalization
      (adjusted odds ratio [aOR]: 1.29; 95% confidence interval [CI]: 1.24 to 1.34) and
      mortality (aOR: 1.24; 95% CI: 1.29 to 1.40). Stratification of T2D by HbA1c
      levels, compared with the reference HF group without T2D, showed U-shaped
      associations with both outcomes. Highest risk categories were HbA1c >9.5%
      (hospitalization, aOR: 1.75; 95% CI: 1.52 to 2.02; mortality, aOR: 1.30; 95% CI:
      1.24 to 1.47) and <5.5% (hospitalization, aOR: 1.42; 95% CI: 1.12 to 1.80;
      mortality, aOR: 1.29; 95% CI: 1.10 to 1.51, respectively). T2D group with change
      in HbA1c of >1% decrease was associated with hospitalization (aOR: 1.33; 95% CI:
      1.18 to 1.49) and mortality (aOR: 1.36; 95% CI: 1.24 to 1.48). T2D drug group
      associations with hospitalization were no medication (aOR: 1.12; 95% CI: 1.04 to
      1.19), oral antihyperglycemic only (aOR: 1.34; 95% CI: 1.27 to 1.41), oral
      antihyperglycemic+insulin (aOR: 1.36; 95% CI: 1.21 to 1.52), and insulin only
      (aOR: 1.61; 95% CI: 1.43 to 1.81); and with mortality for the same drug groups
      were 1.31 (95% CI: 1.23 to 1.39), 1.16 (95% CI: 1.11 to 1.22), 1.19 (95% CI: 1.06
      to 1.34), and 1.43 (95% CI: 1.31 to 1.57), respectively. The T2D group with
      reduced drug treatments were associated with hospitalization (aOR: 2.13; 95% CI:
      1.68 to 2.69) and mortality (aOR: 2.09; 95% CI: 1.81 to 2.41). CONCLUSIONS: In
      the general HF population, T2D stratified by glycemic control and drug treatments
      showed differential risk associations. Routine measures of dynamic diabetes
      status provide important prognostic indication of poor outcomes in HF.

PMID- 29032133
TI  - Heart Rate in Preserved Ejection Fraction Heart Failure.

PMID- 29032132
TI  - Prognostic Importance of Temporal Changes in Resting Heart Rate in Heart Failure
      and Preserved Ejection Fraction: From the TOPCAT Study.
AB  - OBJECTIVES: The aim of this study was to examine the relationship between
      baseline heart rate (HR), change in HR from a preceding visit, and time-updated
      HR with subsequent outcomes in patients with heart failure with preserved
      ejection fraction (HFpEF) in the TOPCAT (Treatment of Preserved Cardiac Function
      Heart Failure With an Aldosterone Antagonist) trial. BACKGROUND: Higher resting
      HR and increase in HR over time in patients with heart failure are associated
      with adverse outcomes. Whether these relationships between HR and prognosis are
      also observed in patients with HFpEF requires further assessment. METHODS: In
      1,767 patients enrolled in the TOPCAT trial from the Americas, the associations
      between baseline resting HR and change in HR from the preceding visit and
      clinical outcomes were examined using Cox proportional hazards models, along with
      the association between HR at each visit and outcome. RESULTS: Both baseline HR
      (adjusted hazard ratio: 1.08; 95% confidence interval: 1.04 to 1.12) and change
      in HR from the preceding visit (adjusted hazard ratio: 1.09; 95% confidence
      interval: 1.05 to 1.14; p < 0.001 per 5 beats/min higher HR), after adjusting for
      covariates, were associated with a higher risk for the primary endpoint of
      cardiovascular death, hospitalization for HF, or aborted cardiac arrest. Time
      updated resting HR at each visit was also associated with risk (adjusted hazard
      ratio: 1.11; 95% confidence interval: 1.07 to 1.15; p < 0.001 per 5 beats/min
      higher HR). Furthermore, a rise in resting HR of approximately 10 beats/min,
      beginning approximately 10 days prior to the primary endpoint, was observed.
      CONCLUSIONS: Baseline resting HR and change in HR over time predict outcomes in
      patients with HFpEF, as does time-updated HR during follow-up. These data suggest
      that frequent outpatient monitoring of HR, possibly with remote technologies, may
      identify patients with HFpEF who may be at increased risk for rehospitalization
      or death.

PMID- 29032134
TI  - Left Ventricular Filling Pressures in Heart Failure With Preserved Ejection
      Fraction: Is the Tail Now Wagging the Dog?

PMID- 29032135
TI  - Glucose-Lowering Therapies in Patients With Concomitant Diabetes Mellitus and
      Heart Failure: Finding the "Sweet Spot".

PMID- 29032136
TI  - A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy
      and Safety of the Oral Soluble Guanylate Cyclase Stimulator: The VICTORIA Trial.
AB  - This trial sought to evaluate whether vericiguat, a novel oral soluble guanylate
      cyclase (sGC) stimulator, was superior to placebo, on a background of standard of
      care, in increasing the time to the first occurrence of the composite endpoints
      of cardiovascular (CV) death and heart failure (HF) hospitalization in patients
      with HF with reduced ejection fraction (HFrEF). Deficiency in sGC-derived cyclic
      guanosine monophosphate (cGMP) causes both myocardial dysfunction and impaired
      endothelium-dependent vasomotor regulation that includes the myocardial
      microcirculation. Experimental studies have suggested multiple potential benefits
      of sGC stimulators including prevention, or even reversal, of left ventricular
      hypertrophy and fibrosis, as well as reduction of ventricular afterload through
      both systemic and pulmonary vasodilation. Hence, restoration of sufficient nitric
      oxide (NO)-sGC-cGMP signaling has been proposed as an important treatment target
      in HF. Vericiguat has been shown to directly stimulate sGC and enhance sGC
      sensitivity to endogenous NO. Available phase IIb data in HFrEF patients indicate
      vericiguat is safe and well-tolerated, and exploratory analyses indicate that it
      results in a dose-dependent, clinically significant reduction in N-terminal pro-B
      type natriuretic peptide (NT-proBNP) at the highest tested dose. VICTORIA
      (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection
      Fraction) is a randomized, placebo-controlled, parallel group, multicenter,
      double-blind, event-driven phase 3 trial of vericiguat in subjects with HFrEF.
      Approximately 4,872 subjects will be randomized to evaluate the efficacy and
      safety of vericiguat compared with placebo on a background of standard of care.
      After a screening phase of up to 30 days, eligible subjects will be treated until
      the required number of cardiovascular deaths is observed. The estimated median
      follow-up duration is approximately 18 months. All subjects will be followed
      until study completion to assess for the occurrence of endpoint events. VICTORIA
      will establish the efficacy and safety of vericiguat on cardiovascular death and
      HF hospitalization in patients with HFrEF. (A Randomized Parallel-Group, Placebo
      Controlled, Double-Blind, Event-Driven, Multi-Center Pivotal Phase III Clinical
      Outcome Trial of Efficacy and Safety of the Oral sGC Stimulator Vericiguat in
      Subjects With Heart Failure With Reduced Ejection Fraction [HFrEF]-VerICiguaT
      Global Study in Subjects With Heart Failure With Reduced Ejection Fraction
      [VICTORIA]; NCT02861534).

PMID- 29032137
TI  - The Risks and Benefits of Moderate Alcohol Consumption: There Remains Much to
      Learn.

PMID- 29032138
TI  - Wedge Pressure Rather Than Left Ventricular End-Diastolic Pressure Predicts
      Outcome in Heart Failure With Preserved Ejection Fraction.
AB  - OBJECTIVES: This study sought to compare the prognostic power of left ventricular
      end-diastolic pressure (LVEDP) and pulmonary arterial wedge pressure (PAWP) in
      heart failure with preserved ejection fraction (HFpEF). BACKGROUND: It is broadly
      accepted that direct measurement of LVEDP in HFpEF more robustly reflects left
      ventricular hemodynamics than PAWP. METHODS: A total of 173 consecutive HFpEF
      patients were prospectively enrolled. Of these, 152 patients fulfilled registry
      inclusion criteria. Study participants underwent clinical evaluation, lung
      function tests, echocardiography, cardiac magnetic resonance, coronary
      angiography, and invasive hemodynamic assessments with PAWP and LVEDP
      measurements in 1 procedure. The study endpoint was defined as hospitalization
      for heart failure or cardiac death. RESULTS: A modest pressure difference (2.0 +/
      4.4 mm Hg) was observed between PAWP (21.5 +/- 5.6 mm Hg) and LVEDP (19.5 +/-
      5.2 mm Hg) at baseline. After a mean follow-up of 23.5 +/- 21.3 months, PAWP was
      predictive of outcome (p = 0.010), whereas LVEDP was not (p = 0.261) by Kaplan
      Meier curves. By multivariate regression analysis, diffusion capacity of carbon
      monoxide (DLCO) was the only parameter that was independently related to the
      pressure difference between PAWP and LVEDP. When patients were stratified
      according to DLCO between <=45% and >45%, those in the low DLCO group were found
      to have a more pronounced pressure drop between PAWP and LVEDP (3.1 +/- 4.8 mm Hg
      vs. 0.8 +/- 3.8 mm Hg, respectively; p = 0.031) and to be in more advanced
      disease stages. CONCLUSIONS: Our data indicate that PAWP but not LVEDP is
      associated with outcome in HFpEF. A more pronounced difference between PAWP and
      LVEDP and more advanced disease is found in patients with low DLCO.

PMID- 29032139
TI  - Effects of Vildagliptin on Ventricular Function in Patients With Type 2 Diabetes
      Mellitus and Heart Failure: A Randomized Placebo-Controlled Trial.
AB  - OBJECTIVES: This study sought to examine the safety of the dipeptidyl peptidase-4
      inhibitor, vildagliptin, in patients with heart failure and reduced ejection
      fraction. BACKGROUND: Many patients with type 2 diabetes mellitus have heart
      failure and it is important to know about the safety of new treatments for
      diabetes in these individuals. METHODS: Patients 18 to 85 years of age with type
      2 diabetes and heart failure (New York Heart Association functional class I to
      III and left ventricular ejection fraction [LVEF] <0.40) were randomized to 52
      weeks treatment with vildagliptin 50 mg twice daily (50 mg once daily if treated
      with a sulfonylurea) or matching placebo. The primary endpoint was between
      treatment change from baseline in echocardiographic LVEF using a noninferiority
      margin of -3.5%. RESULTS: A total of 254 patients were randomly assigned to
      vildagliptin (n = 128) or placebo (n = 126). Baseline LVEF was 30.6 +/- 6.8% in
      the vildagliptin group and 29.6 +/- 7.7% in the placebo group. The adjusted mean
      change in LVEF was 4.95 +/- 1.25% in vildagliptin treated patients and 4.33 +/-
      1.23% in placebo treated patients, a difference of 0.62 (95% confidence interval
      [CI]: -2.21 to 3.44; p = 0.667). This difference met the predefined
      noninferiority margin of -3.5%. Left ventricular end-diastolic and end-systolic
      volumes increased more in the vildagliptin group by 17.1 ml (95% CI: 4.6 to 29.5
      ml; p = 0.007) and 9.4 ml (95% CI: -0.49 to 19.4 ml; p = 0.062), respectively.
      Decrease in hemoglobin A1c from baseline to 16 weeks, the main secondary
      endpoint, was greater in the vildagliptin group: -0.62% (95% CI: -0.93 to -0.30%;
      p < 0.001; -6.8 mmol/mol; 95% CI: -10.2 to -3.3 mmol/mol). CONCLUSIONS: Compared
      with placebo, vildagliptin had no major effect on LVEF but did lead to an
      increase in left ventricular volumes, the cause and clinical significance of
      which is unknown. More evidence is needed regarding the safety of dipeptidyl
      peptidase-4 inhibitors in patients with heart failure and left ventricular
      systolic dysfunction. (Effect of Vildagliptin on Left Ventricular Function in
      Patients With Type 2 Diabetes and Congestive Heart Failure; NCT00894868).

PMID- 29032140
TI  - Heart Failure With Mid-Range (Borderline) Ejection Fraction: Clinical
      Implications and Future Directions.
AB  - Heart failure (HF) with borderline ejection fraction was first defined in 2013 in
      the American College of Cardiology/American Heart Association guidelines as the
      presence of the typical symptoms of HF and a left ventricular ejection fraction
      (LVEF) of 41% to 49%. In 2016, the European Society of Cardiology specified HF
      with mid-range ejection fraction (HFmrEF) as LVEF of 40% to 49%. This range of
      LVEF is less well studied compared with HF with preserved ejection fraction
      (HFpEF) and HF with reduced ejection fraction (HFrEF). Although there are
      effective, guideline-directed medical therapies for patients with HFrEF, no
      therapies thus far show measurable benefit in HFpEF. Patients with HFmrEF have a
      clinical profile and prognosis that are closer to those of patients with HFpEF
      than those of HFrEF, with certain distinctions. Whether these patients represent
      a unique and dynamic HF group that may benefit from targeted therapies known to
      be beneficial in patients with HFrEF, such as neurohormonal blockade, requires
      further study. This review summarizes what is known about the clinical
      epidemiology, pathophysiology, and prognosis for patients with HFmrEF and how
      these features compare with the more well-studied HF groups. Although recommended
      treatments currently focus on aggressive management of comorbidities, we
      summarize the studies that identify a potential signal for beneficial therapies.
      Future studies are needed to not only better characterize the HFmrEF population
      but to also determine effective management strategies to reduce the high
      cardiovascular morbidity and mortality burden on this phenotype of patients with
      HF.

PMID- 29032142
TI  - RAZA: A Rapid 3D z-crossings algorithm to segment electron tomograms and extract
      organelles and macromolecules.
AB  - Resolving the 3D architecture of cells to atomic resolution is one of the most
      ambitious challenges of cellular and structural biology. Central to this process
      is the ability to automate tomogram segmentation to identify sub-cellular
      components, facilitate molecular docking and annotate detected objects with
      associated metadata. Here we demonstrate that RAZA (Rapid 3D z-crossings
      algorithm) provides a robust, accurate, intuitive, fast, and generally applicable
      segmentation algorithm capable of detecting organelles, membranes, macromolecular
      assemblies and extrinsic membrane protein domains. RAZA defines each continuous
      contour within a tomogram as a discrete object and extracts a set of 3D
      structural fingerprints (major, middle and minor axes, surface area and volume),
      enabling selective, semi-automated segmentation and object extraction. RAZA takes
      advantage of the fact that the underlying algorithm is a true 3D edge detector,
      allowing the axes of a detected object to be defined, independent of its random
      orientation within a cellular tomogram. The selectivity of object segmentation
      and extraction can be controlled by specifying a user-defined detection tolerance
      threshold for each fingerprint parameter, within which segmented objects must
      fall and/or by altering the number of search parameters, to define
      morphologically similar structures. We demonstrate the capability of RAZA to
      selectively extract subgroups of organelles (mitochondria) and macromolecular
      assemblies (ribosomes) from cellular tomograms. Furthermore, the ability of RAZA
      to define objects and their contours, provides a basis for molecular docking and
      rapid tomogram annotation.

PMID- 29032141
TI  - Moderate Alcohol Consumption Is Associated With Lower Risk for Heart Failure But
      Not Atrial Fibrillation.
AB  - OBJECTIVES: The aim of this study was to assess the hypothesis that alcohol
      consumption is associated with onset of atrial fibrillation (AF) and/or heart
      failure (HF). BACKGROUND: The connection between ethanol intake and AF or HF
      remains controversial. METHODS: The study population was 22,824 AF- or HF-free
      subjects (48% men, age >=35 years) randomly recruited from the general population
      included in the Moli-sani study, for whom complete data on HF, AF, and alcohol
      consumption were available. The cohort was followed up to December 31, 2015, for
      a median of 8.2 years (183,912 person-years). Incident cases were identified
      through linkage to the Molise regional archive of hospital discharges. Hazard
      ratios were calculated using Cox proportional hazard models and cubic spline
      regression. RESULTS: A total of 943 incident cases of HF and 554 of AF were
      identified. In comparison with never drinkers, both former and occasional
      drinkers showed comparable risk for developing HF. Drinking alcohol in the range
      of 1 to 4 drinks/day was associated with a lower risk for HF, with a 22% maximum
      risk reduction at 20 g/day, independent of common confounders. In contrast, no
      association of alcohol consumption with onset of AF was observed. Very similar
      results were obtained after restriction of the analyses to regular or only wine
      drinkers or according to sex, age, social status, or adherence to the
      Mediterranean diet. CONCLUSIONS: Consumption of alcohol in moderation was
      associated with a lower incidence of HF but not with development of AF.

PMID- 29032143
TI  - Effects of Cr(VI) on Ca2+-ATPase activity in the earthworm Eisenia andrei.
AB  - The effect of Cr(VI) as a soil contaminant on the edaphic worm Eisenia andrei was
      studied by evaluating the activity of Ca2+-ATPase in the intestinal mucosa. In
      eukaryotes, Ca2+-ATPase is a key mediator of cell signaling although
      comparatively little is known about its activity in earthworms. Size and
      anatomical constraints (i.e. small and complex) led us to develop and optimize a
      cyto-biochemical method to measure Ca2+-ATPase activity in earthworms. The
      principal site of enzyme activity was found to be the post clitellar intestinal
      tract; immunohistochemistry then identified plasma membrane Ca2+-ATPase (PMCA
      ATPase) in the apical area of the intestinal epithelium. Earthworms exposed for
      28days to OECD soil contaminated with 1, 2, and 15mg/Kg Cr(VI) demonstrated about
      70% inhibition of Ca2+-ATPase activity at the low Cr (VI) concentration (the half
      of the Italian law limit for residential areas), rising to approximately 84%
      inhibition at the highest concentration. Reduced enzyme activity was accompanied
      by decreased enzyme content and reduced lysosomal membrane stability (LMS), which
      is a well established early warning biomarker of stress. These data demonstrate
      the potential utility of Ca2+-ATPase activity as a sensitive parameter with which
      to detect environmental stress in earthworms.

PMID- 29032146
TI  - microRNA single polynucleotide polymorphism influences on microRNA biogenesis and
      mRNA target specificity.
AB  - microRNAs (miRNAs) are nowadays recognized as an essential component of gene
      regulatory networks. Furthermore, deregulation of miRNAs expression often
      contributes to human pathologies. Recently, a substantial number of single
      nucleotide polymorphism (SNPs) and rare mutations within pri-, pre- and mature
      miRNA sequences have been reported. These miRNA SNPs have often been associated
      with human disease. However, due to the complexity of miRNA biogenesis and the
      genome-wide functional effects of miRNAs, the determination of biological
      consequences of these miRNA SNPs remains challenging. Despite an increasing
      number of reports linking miRNA SNPs with human pathologies, few reports have
      analyzed the mechanism by which miRNA-SNPs contribute to disease pathogenesis. In
      this review, we discuss how single polynucleotide polymorphisms in miRNAs genes
      may influence miRNAs expression and function and thus potentially alter disease
      pathogenesis.

PMID- 29032145
TI  - Genetic association analysis of vitamin D receptor gene polymorphisms and obesity
      related phenotypes.
AB  - Vitamin D has been established as a key factor in the development of obesity
      through the vitamin D receptor (VDR). The aim of this study was to investigate
      the contribution of the VDR gene to obesity-related phenotypes in a population of
      Caucasian young adults. The study population consisted of 701 healthy Spanish
      young adults (mean age 20.41+/-2.48). Three single-nucleotide polymorphisms
      (SNPs) of VDR (TaqI, BsmI and FokI) were selected as genetic markers. Body
      composition measurements including weight, body mass index (BMI), fat mass (FM),
      percentage of fat mass (PFM), fat-free mass (FFM) and visceral fat level (VFL)
      were analysed. Differences in obesity traits across the genotypes were determined
      using analysis of covariance (ANCOVA). The FokI polymorphism showed a significant
      association with PFM across the whole population after adjusting for age and sex
      (p=0.022). Age-adjusted analysis revealed an association between body weight and
      the TaqI and BsmI SNPs in males (p=0.033 and p=0.028, respectively). However,
      these positive findings did not remain significant after applying the Bonferroni
      correction for multiple testing. Our findings suggest that VDR genetic variants
      are unlikely to play a major role in obesity-related phenotypes in a population
      of Caucasian young adults.

PMID- 29032147
TI  - High bone marrow miR-19b level predicts poor prognosis and disease recurrence in
      de novo acute myeloid leukemia.
AB  - Oncogenic role of miR-19 family has been identified in human cancers especially
      in lymphoid malignancies. However, to date, little studies investigated the role
      of miR-19 family in myeloid malignancies. Herein, we examined miR-19a/b
      expression and explored its clinical significance in de novo acute myeloid
      leukemia (AML). The detection of miR-19a/b expression was performed by real-time
      quantitative PCR in bone marrow mononuclear cells of 113 patients and 42 healthy
      donors. Both miR-19a/b levels were significantly increased in AML patients in
      contrast to controls. Patients with miR-19a/b overexpression were more frequently
      occurred in female, and had an older age. Moreover, cases with miR-19a
      overexpression had a higher frequency of U2AF1, C-KIT and CEBPA mutations,
      whereas miR-19b overexpressed cases harbored U2AF1 and IDH1/2 mutations. There
      was no significant association of miR-19a overexpression with complete remission
      (CR) rate and overall survival (OS) among whole-cohort AML, non-M3 AML, and
      cytogenetically normal AML (CN-AML). However, although miR-19b overexpression was
      not correlated with CR rate, patients with miR-19b overexpression presented
      significantly shorter OS in whole-cohort AML and a trend in non-M3 AML and CN-AML
      patients. Importantly, our data also showed that miR-19a/b expression level at CR
      phase was lower than diagnosis time, and was returned to primary level even
      higher when at relapse phase. Our findings revealed that miR-19a/b overexpression
      were frequent events in de novo AML patients. Moreover, up-regulation of miR-19b
      expression was associated with poor prognosis and disease recurrence in AML.

PMID- 29032148
TI  - Predisposition of IL-1beta (-511 C/T) polymorphism to renal and hematologic
      disorders in Indian SLE patients.
AB  - OBJECTIVE: To see the role of IL-1beta gene polymorphisms to disease
      susceptibility in Indian SLE patients. MATERIALS AND METHODS: This case-control
      study included 200 SLE patients and 201 controls. Serum levels of IL-1beta and
      anti-C1q antibodies were measured by multiplex immunoassay and ELISA
      respectively. Genotyping of SNPs in IL-1beta (-511C/T and +3954C/T) were
      performed by PCR-RFLP method. Autoantibody profile was done in 141 SLE patients.
      RESULTS: Mean serum levels of IL-1Beta were significantly higher (10.9+/
      5.3pg/ml) in patients compared to controls (7.0+/-2.0pg/ml) (p<0.0001).
      Similarly, mean levels of IL-1beta were significantly elevated among patients
      with renal and hematologic manifestations. IL-1Beta levels were negatively
      correlated with hemoglobin concentration (r=-0.25, p=0.001). A statistically
      significant difference was observed for IL-1beta -511CC genotypes (OR=2.9,
      p=0.0068, Pc=0.0136) in patients with Lupus Nephritis (LN) as compared to SLE
      patients without nephritis. The IL-1beta+3954CT genotype (OR=2.0, p=0.0032,
      Pc=0.0064) and +3954T allele (OR=1.9, p=0.0017, Pc=0.0034) showed significantly
      higher frequency among patients as compared to controls. Furthermore, the -511C
      allele showed higher prevalence in patients with renal (OR=1.6, p=0.0335) and
      hematologic (OR=1.6, p=0.0326) manifestations among SLE patients. CONCLUSION: IL
      1beta gene polymorphisms appear to confer susceptibility to the disease in Indian
      SLE patients.

PMID- 29032149
TI  - TG haplotype in the LRP8 is associated with myocardial infarction in south Indian
      population.
AB  - Myocardial infarction (MI) is a complex multifactorial cardiovascular disease.
      India experiences a much greater burden of MI, also suggesting an experimental
      increase of this burden in the future. The absolute reasons for MI are context
      dependent and differ with different geographical settings. Several reports
      indicate that SNPs that are associated with certain diseases in other populations
      may not be associated with Indian population. It is, therefore, important to
      validate the association of SNPs. Low density lipoprotein receptor related
      protein 8 (LRP8) gene plays central role in human lipoprotein metabolism as it
      facilitates the clearance of bad cholesterol LDL, VLDL from plasma and is
      reported to be associated with MI in the western population. However, this gene
      has not been studied in the South Indian population. We aim to test the role of
      the LRP8 gene variants correlating with the lipid profile in MI patients in South
      Indian population. We sequenced regions of SNPs rs10788952, rs7546246, rs2297660
      and rs5174 of LRP8 in 100 MI patients and 100 age-matched controls. Our result
      revealed a total of 4 variations. None of the SNPs were significantly associated
      with MI (p>0.973). Interestingly, haplotype based association analysis showed TG
      and CG of rs10788952 and rs7546246 significantly associated with MI (p<0.01 and
      p<0.00005) and in particular, haplotype TG was positively correlated with the
      risk of MI, as this increased the LDL and total cholesterol level in MI patients
      in south Indians. Our results suggest that haplotype TG is a risk factor for MI
      in South Indian population.

PMID- 29032150
TI  - Functional analysis of schizophrenia genes using GeneAnalytics program and
      integrated databases.
AB  - Schizophrenia (SCZ) is a chronic debilitating neuropsychiatric disorder with
      multiple risk factors involving numerous complex genetic influences. We examined
      and updated a master list of clinically relevant and susceptibility genes
      associated with SCZ reported in the literature and genomic databases dedicated to
      gene discovery for characterization of SCZ genes. We used the commercially
      available GeneAnalytics computer-based gene analysis program and integrated
      genomic databases to create a molecular profile of the updated list of 608 SCZ
      genes to model their impact in select categories (tissues and cells, diseases,
      pathways, biological processes, molecular functions, phenotypes and compounds)
      using specialized GeneAnalytics algorithms. Genes for schizophrenia were
      predominantly expressed in the cerebellum, cerebral cortex, medulla oblongata,
      thalamus and hypothalamus. Psychiatric/behavioral disorders incorporating SCZ
      genes included ADHD, bipolar disorder, autism spectrum disorder and alcohol
      dependence as well as cancer, Alzheimer's and Parkinson's disease, sleep
      disturbances and inflammation. Function based analysis of major biological
      pathways and mechanisms associated with SCZ genes identified glutaminergic
      receptors (e.g., GRIA1, GRIN2, GRIK4, GRM5), serotonergic receptors (e.g., HTR2A,
      HTR2C), GABAergic receptors (e.g., GABRA1, GABRB2), dopaminergic receptors (e.g.,
      DRD1, DRD2), calcium-related channels (e.g., CACNA1H, CACNA1B), solute
      transporters (e.g., SLC1A1, SLC6A2) and for neurodevelopment (e.g., ADCY1, MEF2C,
      NOTCH2, SHANK3). Biological mechanisms involving synaptic transmission,
      regulation of membrane potential and transmembrane ion transport were identified
      as leading molecular functions associated with SCZ genes. Our approach to
      interrogate SCZ genes and their interactions at various levels has increased our
      knowledge and insight into the disease process possibly opening new avenues for
      therapeutic intervention.

PMID- 29032151
TI  - Sertoli cell specific knockdown of RAR-related orphan receptor (ROR) alpha at
      puberty reduces sperm count in rats.
AB  - Globally, there is an alarming decline in sperm count. Very often hormonal
      supplementation fails to restore normal sperm count. Sertoli cells (Sc) present
      within seminiferous tubules provide appropriate niche and factors required for
      the differentiation of germ cells (Gc) into mature sperm (spermatogenesis).
      Functionally compromised Sc may be one of the reasons for failure of hormones to
      facilitate normal spermatogenesis. Although role of secretory proteins and
      signaling molecules of Sc has been studied well, role of transcription factors
      regulating sperm count has not been addressed appropriately. Retinoic acid
      receptor-related orphan receptor (ROR)-alpha is one of such transcription factors
      reported in testis but its role in testicular function is not yet known. In a
      separate study, we found abundant ROR-alpha binding sites on promoter regions of
      several genes upregulated in pubertal rat Sc as compared to infant Sc.
      Immunostaining studies also revealed presence of ROR alpha in nucleus of pubertal
      Sc. We generated a transgenic knockdown rat model expressing shRNA targeted to
      ROR-alpha under Sc specific promoter, which is transcriptionally active only at
      and after puberty. ROR-alpha knockdown animals were found to have abnormal
      association of Sc and Gc, including Gc sloughing and restricted release of sperm.
      The knockdown animals displayed compromised spermatogenesis leading to
      significant reduction in sperm count. This is the first report describing the Sc
      specific role of ROR-alpha in maintaining quantitatively normal sperm output.
      Identification of various such molecules can generate avenues to limit or reverse
      an alarmingly declining sperm count witnessed globally in men.

PMID- 29032152
TI  - Structure function characterization of the ELL Associated Factor (EAF) from
      Schizosaccharomyces pombe.
AB  - EAF (ELL Associated Factor) proteins interact with the transcription elongation
      factor, ELL (Eleven nineteen Lysine rich Leukemia) and enhance its ability to
      stimulate RNA polymerase II-mediated transcriptional elongation in vitro.
      Schizosaccharomyces pombe contains a single homolog of EAF (SpEAF), which is not
      essential for survival of S. pombe in contrast to its essential higher eukaryotic
      homologs. The physiological role of SpEAF is not well understood. In this study,
      we show that S. pombe EAF is important in regulating growth of S. pombe cells
      during normal growth conditions. Moreover, SpEAF is also essential for survival
      under conditions of DNA damage, while its deletion does not affect growth under
      environmental stress conditions. Our in vivo structure-function studies further
      demonstrate that while both the amino and carboxyl terminal domains of SpEAF
      possess the potential to activate transcription, only the amino terminal domain
      of SpEAF is involved in interaction with the S. pombe ELL protein. The carboxyl
      terminus of SpEAF is required for rescue of the growth defect under normal and
      DNA damaging conditions that is associated with the absence of SpEAF. Using
      bioinformatics and circular dichroism spectroscopy, we show that the carboxyl
      terminus of SpEAF has a disordered conformation. Furthermore, addition of
      trifluoroethanol triggered its transition from a disordered to alpha-helical
      conformation. Taken together, the results presented here identify novel
      structural and functional features of SpEAF protein, providing insights into how
      EAF proteins may enforce transcriptional control of gene expression.

PMID- 29032153
TI  - Metformin overcomes high glucose-induced insulin resistance of podocytes by
      pleiotropic effects on SIRT1 and AMPK.
AB  - Podocyte insulin sensitivity is critical for glomerular function, and the loss of
      appropriate insulin signaling leads to alterations and disorders featuring
      diabetic nephropathy. Energy-sensing pathways, such as AMP-dependent protein
      kinase (AMPK) and protein deacetylase SIRT1, have been shown to play an important
      role in insulin resistance. The absence of a stimulating effect of insulin on
      glucose uptake into podocytes after exposure to hyperglycemic conditions has been
      demonstrated to be related to a decreased level and activity of SIRT1 protein,
      leading to reduced AMPK phosphorylation. The present work was undertaken to
      investigate metformin's ability to restore the insulin responsiveness of
      podocytes by regulating SIRT1 and AMPK activities. Primary rat podocytes cultured
      with standard or high glucose concentrations for 5days were transfected with
      siRNAs targeting SIRT1, AMPKalpha1, or AMPKalpha2. SIRT1 activity was measured by
      a fluorometric method. Insulin-stimulated changes in glucose uptake were used to
      detect insulin resistance. Podocyte permeability was measured by a transmembrane
      albumin flux assay to examine podocytes functioning. Our results demonstrated
      that metformin activated SIRT1 and AMPK, prevented hyperglycemia-induced
      reduction of SIRT1 protein levels, ameliorated glucose uptake into podocytes, and
      decreased glomerular filtration barrier permeability. Furthermore, metformin
      activated AMPK in a SIRT1-independent manner, as the increase in AMPK
      phosphorylation after metformin treatment was not affected by SIRT1
      downregulation. Therefore, the potentiating effect of metformin on insulin
      resistant podocytes seemed to be dependent on AMPK, as well as SIRT1 activity,
      establishing multilateral effects of metformin action.

PMID- 29032154
TI  - Are We Ready for Adjuvant Sunitinib in High-risk Renal Cell Carcinoma?

PMID- 29032155
TI  - Functional characterisation of glutathione export from the rat lens.
AB  - In this study, we have investigated whether the lens was capable of exporting the
      antioxidant glutathione. Pairs of rat lenses were cultured in isosmotic
      artificial aqueous humour for one, two, three, or six hours in low oxygen
      conditions (90% N2, 5% CO2, 5% O2), and reduced glutathione (GSH) and oxidised
      glutathione (GSSG) levels measured in the media and lenses. We show that the rat
      lens is capable of releasing ~5 nmol GSH for each time point suggesting that GSH
      release is regulated since it does not appreciably increase over time. We also
      demonstrated that the predominant form of glutathione released was the reduced
      form. We next cultured lenses in the absence or presence of acivicin, a gamma
      glutamyl transpeptidase (GGT) inhibitor, and found that GSH levels were
      significantly increased (p < 0.001) in the presence of this inhibitor, which
      indicated that GSH released by the lens undergoes degradation into its
      constituent amino acids. GSH release was significantly decreased (p < 0.001) in
      the presence of 100 MUM MK571, a multidrug resistance-associated protein (Mrp)
      inhibitor, suggesting that Mrp transporters mediate GSH efflux from the lens.
      Culturing lenses in low (10 MUM) or high (70 MUM) concentrations of H2O2 for one
      hour significantly increased total glutathione levels (p < 0.05) relative to
      controls, due to the increased release of GSSG. Our results show that in response
      to oxidative stress, the rat lens is able to release GSH or GSSG, thereby serving
      to maintain lens redox state or potentially influence the redox state of nearby
      tissues.

PMID- 29032156
TI  - Suppressor of cytokine signaling 2-12 regulates antimicrobial peptides and
      ecdysteroid signaling pathways in Bombyx mori (Dazao).
AB  - Suppressors of cytokine signaling (SOCS) are a potent negative regulator of
      diverse cytokine-related responses to maintain various physiological processes in
      animals. Here, we obtained the SOCS2-12 gene sequence of Bombyx mori (Dazao)
      (BmSOCS2-12) from the National Center for Biotechnology Information (NCBI) to
      study its expression profile in different tissues, as well as in the immune
      tissues following larval exposure to pathogens. Further, we investigated the role
      of BmSOCS2-12 in producing antimicrobial peptides (AMPs) and as a regulator of
      ecdysteroid signaling transduction. The quantitative real-time PCR analysis
      revealed unequal transcript levels of BmSOCS2-12 in the different tissues,
      however the gene's expression was highest in those of fat body and hemocyte. The
      challenge with pathogens significantly upregulated the transcript level of
      BmSOCS2-12 in both fat body and hemocyte when compared with the control. By
      contrast, recombinant BmSOCS2-12 protein injections strongly suppressed the
      expression of AMPs, while the knockdown of BmSOCS2-12 by double-stranded RNA
      enhanced their production. Administration of 20-hydroxyecdysone significantly
      downregulated the BmSOCS2-12 expression in fat body, and the depletion of BmSOCS2
      12 enhanced the transcript levels of 20-hydroxyecdysone-responsive genes at 48 h.
      Altogether, BmSOCS2-12 may have multiple functional roles in the physiology of B.
      mori (Dazao), since it negatively regulates the expression of AMPs and
      ecdysteroid signaling transduction.

PMID- 29032157
TI  - Effects of fat and exoskeletal mass on the mass scaling of metabolism in
      Carabidae beetles.
AB  - The rate at which organisms metabolize resources and consume oxygen is tightly
      linked to body mass. Typically, there is a sub-linear allometric relationship
      between metabolic rates and body mass (mass-scaling exponent b < 1). The origin
      of this pattern remains one of the most intriguing and hotly debated topics in
      evolutionary physiology. A decrease in mass-specific metabolic rates in larger
      organisms might reflect disproportionate increases in body components with low
      metabolic activity, such as storage and skeletal tissues. Addressing this
      hypothesis, we studied standard metabolic rates, body mass, and fat and
      exoskeletal mass in males and females from 15 species of Carabidae beetles. There
      was a sub-linear allometric relationship of metabolic rate with body mass: b =
      0.72 (phylogeny not considered), b = 0.54 (phylogeny considered). The latter
      exponent was significantly lower than 0.75, which is sometimes regarded as a
      universal exponent value in the mass scaling of metabolic rates. Contrary to our
      hypothesis, the relative contribution of fat and the exoskeleton to body mass
      decreased, rather than increased with body mass, as indicated by the sub-linear
      allometric mass scaling of both components (b < 1). Supporting the role of
      metabolically inert body components in shaping metabolic scaling, the exponents
      (b) for metabolism became slightly smaller (b = 0.70, phylogeny not considered;
      0.52, phylogeny considered) when we removed lipids and the exoskeleton from body
      mass calculations and considered only the lean mass of soft tissue in the mass
      scaling. Overall, our results indicate that, in beetles, the relative content of
      metabolically inert components changes across species according to species
      specific body mass. Nevertheless, we did not find evidence that this changing
      contribution plays a central role in the origin of interspecific metabolic
      scaling in carabids. Our findings stress the need for finding alternative
      explanations, at least in carabids, for the origin of the mass scaling of
      metabolic rates.

PMID- 29032158
TI  - Location affects the management of liver haemangioma: A retrospective cohort
      study.
AB  - BACKGROUND: The location of liver haemangioma may affect surgical decisions, but
      no study has ever examined this issue. METHODS: A retrospective study was
      performed on 338 liver haemangioma patients who visited at clinic. The collected
      data included demographics, location, symptoms and whether surgical treatment was
      performed. For patients with surgical treatment, the collected data included
      radiologic characteristics, surgical procedures, surgical variables,
      postoperative stay, morbidity, and mortality. According to the location, patients
      were divided into left or right group and comparison was made between them.
      RESULTS: Compared to the right group, patients in the left group were more likely
      to have symptoms (P = 0.018), especially patients with 5- to 10-cm haemangiomas
      (P < 0.001). Patients in the left group had higher rates of exophytic lesions and
      gastric outlet compression (63.8% vs 7.1%, 56.5% vs 5.1%, P < 0.001 each), while
      patients in the right group had a higher rate of vessel compression (36.4% vs
      21.7%, P = 0.043). Higher ratio of patients in left group received liver
      resection (75.4% vs 26.3%, P < 0.001). The surgical time, amounts of collected
      blood and autologous transfusion were all greater in the right group (P = 0.008,
      P = 0.001 and P = 0.003, respectively). The postoperative stay was longer in the
      right group (P = 0.007). CONCLUSION: The location of liver haemangioma should be
      considered when making surgical decisions, and it may be one of the main
      considerations for surgical procedures.

PMID- 29032159
TI  - Comparison between different approaches applied in laparoscopic right hemi
      colectomy: A systematic review and network meta-analysis.
AB  - AIM: Several different operative approaches have been applied nowadays in
      laparoscopic right hemi-colectomy. This study aims to evaluate the potential
      benefits of different approaches by conducting a network meta-analysis (NMA).
      METHOD: A comprehensive literature research of the PubMed, Embase, Medline, the
      Cochrane Central Library, Wan Fang and China National Knowledge Infrastructure
      (CNKI) databases was performed. Original articles comparing two of three
      different approaches including medial to lateral (MtL) approach, lateral to
      medial (LtM) approach and cranial to caudal (CtC) approach of laparoscopic right
      colon resection for patients with both neoplastic and benign diseases were
      included. RESULTS: 3 RCTs and 3 NRCTs with a total of 571 patients were included
      in this NMA. The result revealed that LtM approach needs shorter postoperative
      flatus recovery time than both MtL approach with a WMD of 1.40 (95% CI: 0.13 to
      2.67, P < 0.05) and CtC approach (WMD = -1.25, 95% CI: -1.90 to -0.61, P < 0.05).
      The length of hospital stay of LtM approach is shorter than that of MtL approach
      (WMD = 0.29, 95% CI: 0.08 to 0.50, P < 0.05). CtC approach can achieve less
      postoperative complications (OR = 3.37, 95% CI: 1.06 to 10.70, P < 0.05) compared
      with MtL approach. CONCLUSION: All three approaches are safe and acceptable in
      laparoscopic right hemi-colectomy since the pooled evidence revealed that most
      aspects of different approaches are comparable in general. The postoperative
      flatus recovery time and hospitalization time of LtM approach is shorter compared
      with MtL approach. And CtC approach may have slight superiority in postoperative
      complications compared with MtL approach.

PMID- 29032144
TI  - Peroxisome proliferator-activated receptor gamma (PPARgamma): A master gatekeeper
      in CNS injury and repair.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a widely
      expressed ligand-modulated transcription factor that governs the expression of
      genes involved in inflammation, redox equilibrium, trophic factor production,
      insulin sensitivity, and the metabolism of lipids and glucose. Synthetic
      PPARgamma agonists (e.g. thiazolidinediones) are used to treat Type II diabetes
      and have the potential to limit the risk of developing brain injuries such as
      stroke by mitigating the influence of comorbidities. If brain injury develops,
      PPARgamma serves as a master gatekeeper of cytoprotective stress responses,
      improving the chances of cellular survival and recovery of homeostatic
      equilibrium. In the acute injury phase, PPARgamma directly restricts tissue
      damage by inhibiting the NFkappaB pathway to mitigate inflammation and
      stimulating the Nrf2/ARE axis to neutralize oxidative stress. During the chronic
      phase of acute brain injuries, PPARgamma activation in injured cells culminates
      in the repair of gray and white matter, preservation of the blood-brain barrier,
      reconstruction of the neurovascular unit, resolution of inflammation, and long
      term functional recovery. Thus, PPARgamma lies at the apex of cell fate decisions
      and exerts profound effects on the chronic progression of acute injury
      conditions. Here, we review the therapeutic potential of PPARgamma in stroke and
      brain trauma and highlight the novel role of PPARgamma in long-term tissue
      repair. We describe its structure and function and identify the genes that it
      targets. PPARgamma regulation of inflammation, metabolism, cell fate
      (proliferation/differentiation/maturation/survival), and many other processes
      also has relevance to other neurological diseases. Therefore, PPARgamma is an
      attractive target for therapies against a number of progressive neurological
      disorders.

PMID- 29032160
TI  - Multimodal treatment including hysterectomy improves survival in patients with
      locally advanced cervical cancer: A population-based, propensity score-matched
      analysis.
AB  - BACKGROUND: To evaluate the therapeutic value of multimodal treatment including
      hysterectomy in locally advanced cervical squamous cell carcinoma (SCC). METHODS:
      We retrospectively reviewed patients diagnosed with International Federation of
      Gynecology and Obstetrics (FIGO) stage IIB-III cervical SCC and received
      chemotherapy and radiotherapy with or without hysterectomy between 2000 and 2013
      using the Surveillance, Epidemiology, and End Results program. Propensity score
      matching was used to balance baseline characteristics of included patients.
      Univariate and multivariate Cox regression analyses were performed to determine
      prognostic factors for cervical cancer specific-survival (CCSS) and overall
      survival (OS). RESULTS: We identified 2473 patients and 522 pairs of patients
      were completely matched with each other. In the unmatched population, patients
      with younger age, non-black race, poorly/undifferentiated disease, FIGO stage IIB
      disease, and node-positive disease were more likely to receive additional
      hysterectomy. Additional hysterectomy was associated with better CCSS and OS in
      unmatched and matched populations. Moreover, when evaluating the survival
      difference by FIGO stage, only stage IIB disease retained statistical
      significance but not for stage III disease in unmatched and matched populations.
      CONCLUSIONS: Our results suggest that multimodal treatment including hysterectomy
      might improve survival outcomes in patients with locally advanced cervical SCC,
      especially for stage IIB disease.

PMID- 29032161
TI  - Appropriate use criteria on transesophageal echocardiography: a cost-effective
      means to improve the quality of health services.

PMID- 29032162
TI  - De-identification of medical records using conditional random fields and long
      short-term memory networks.
AB  - The CEGS N-GRID 2016 Shared Task 1 in Clinical Natural Language Processing
      focuses on the de-identification of psychiatric evaluation records. This paper
      describes two participating systems of our team, based on conditional random
      fields (CRFs) and long short-term memory networks (LSTMs). A pre-processing
      module was introduced for sentence detection and tokenization before de
      identification. For CRFs, manually extracted rich features were utilized to train
      the model. For LSTMs, a character-level bi-directional LSTM network was applied
      to represent tokens and classify tags for each token, following which a decoding
      layer was stacked to decode the most probable protected health information (PHI)
      terms. The LSTM-based system attained an i2b2 strict micro-F1 measure of 0.8986,
      which was higher than that of the CRF-based system.

PMID- 29032163
TI  - Massively parallel sequencing on human cleavage-stage embryos to detect
      chromosomal abnormality.
AB  - PURPOSE: Next-generation sequencing technology like MPS has recently been
      introduced to perform comprehensive chromosome screening on human trophectoderm
      samples for preimplantation embryo assessment. However, the potential of MPS in
      chromosome analysis of single cell from blastomeres has not yet been
      investigated. METHODS: In this study, 12 couples underwent MPS analysis,
      including 9 balanced translocation carriers and 3 carriers of numerical
      chromosomal abnormalities. Cleavage-stage (Day 3) embryos (n = 105) were biopsied
      with one cell removal. Single cell from blastomeres was processed by whole genome
      amplification (WGA). WGA products were subjected to both MPS and microarray-based
      comparative genomic hybridization (array-CGH). Euploid embryos identified as
      "balanced or normal" were selected for frozen-thawed embryo transfer (FET)
      cycles. RESULTS: Reliable MPS-PGD results as well as array CGH-PGD results were
      obtained for 101 biopsied cleavage-stage embryos. 18.8% (19/101) embryos were
      identified as "euploid and balanced" by both MPS and array-CGH. 20.8% (21/101)
      were unbalanced for the translocation but normal for aneuploidy.26.7% (27/101)
      had aneuploidy and were unbalanced. 33.7% (34/101) showed normal or balanced but
      still had aneuploidy of chromosomes. In identifications of embryo aneuploidy and
      imbalance, MPS and array-CGH showed 100% consistency, with the exception of 4
      samples. After transferring 12 embryos with normal or balanced for every
      chromosome, 1 live birth and 5 ongoing clinical pregnancies were achieved.
      CONCLUSION: In conclusion, as a flexible and cost-effective strategy and higher
      potential accuracy. MPS could be clinically applied to detect numeric abnormality
      of chromosome segments in day 3 preimplantation blastomeres.

PMID- 29032165
TI  - Association between family socioeconomic status and depressive symptoms among
      Chinese adolescents: Evidence from a national household survey.
AB  - Depression is a common mental disorder due to high risk of the adolescence
      development stage. Few studies discussed the association between family
      socioeconomic status (SES) and depression and its mechanism. We aimed to provide
      a national view of depressive symptoms among Chinese adolescents to explore the
      relationship between family SES and depressive symptoms. We used the data from
      the Chinese Family Panel Studies (CFPS). Family SES include family income and
      parents' educational attainment. Depressive symptoms were measured by the Center
      for Epidemiological Study Depression. Family SES was found to be significantly
      associated with adolescents' depressive symptoms. The study indicated that
      adolescents were more likely to have depressive symptoms when family income
      decreased. Poor self-confidence, mathematics performance, and physical health
      were associated with high risk for depressive symptoms. The presence of these
      factors greatly weakened the association between family SES and depressive
      symptoms. Therefore, adolescents' mental health is vulnerable and connected to
      family SES. Physical health, school performance, and self-confidence might be
      important mediators in the pathways of family SES affecting depressive symptoms.
      Prevention and intervention programs are important and necessary to improve the
      mental health of Chinese adolescents, and the effect of family SES should be
      considered in these programs.

PMID- 29032164
TI  - A portable microfluidic Aptamer-Tethered Enzyme Capture (APTEC) biosensor for
      malaria diagnosis.
AB  - There is a critical need for better biosensors for the detection and diagnosis of
      malaria. We previously developed a DNA aptamer that recognises the Plasmodium
      falciparum lactate dehydrogenase (PfLDH) enzyme with high sensitivity and
      specificity. The aptamer was integrated into an Aptamer-Tethered Enzyme Capture
      (APTEC) assay as a laboratory-based diagnostic approach. However, a portable
      equipment-free point-of-care aptamer-mediated biosensor could have a significant
      impact on malaria diagnosis in endemic regions. Here, we present a new concept
      for a malaria biosensor whereby aptamers are coated onto magnetic microbeads for
      magnet-guided capture, wash and detection of the biomarker. A biosensor
      incorporating three separate microfluidic chambers was designed to enable such
      magnet-guided equipment-free colorimetric detection of PfLDH. A series of
      microfluidic biosensor prototypes were optimised to lower rates of inter-chamber
      diffusion, increase sensitivity, and provide a method for point-of-care sample
      testing. The biosensor showed high sensitivity and specificity when detecting
      PfLDH using both in vitro cultured parasite samples and using clinical samples
      from malaria patients. The high performance of the biosensor provides a proof-of
      principle for a portable biosensor that could be adaptable for a variety of
      aptamer-mediated diagnostic scenarios.

PMID- 29032166
TI  - Interpersonal vulnerability among offspring of Holocaust survivors gay men and
      its association with depressive symptoms and life satisfaction.
AB  - The aim of the current study was to examine whether offspring of Holocaust
      survivors (OHS) gay men report higher interpersonal vulnerability in comparison
      to non-OHS gay men, and to further assess whether that vulnerability mediates the
      association between having a Holocaust background and mental health outcomes
      (depressive symptoms and life satisfaction). For this purpose, a community
      dwelling sample of 79 middle-aged and older OHS and 129 non-OHS gay men completed
      measures of hostile-world scenario (HWS) in the interpersonal domain,
      satisfaction from current steady relationship, depressive symptoms and life
      satisfaction. Results indicated that OHS reported higher HWS interpersonal
      vulnerability and lower satisfaction from current relationship in comparison to
      non-OHS gay men. Also, having a Holocaust background had an indirect effect on
      depressive symptoms and life satisfaction through HWS interpersonal vulnerability
      as well as through satisfaction from current relationship. These findings are the
      first to suggest interpersonal vulnerability of older OHS, in comparison to non
      OHS, gay men, and an association between this vulnerability and adverse
      psychological outcomes. This interpersonal vulnerability, possibly representing
      HWS threats of both early family-based trauma and current sexual minority stress,
      along with its implications, should be addressed by practitioners who work with
      older gay men having a Holocaust background.

PMID- 29032167
TI  - Evaluation of embryotoxic and teratogenic effects of the oil extracted from
      Caryocar brasiliense Cambess pulp in rats.
AB  - The objective of this study was to evaluate the maternal, embryotoxic and
      teratogenic effects of Caryocar brasiliense pulp oil (OPCB), oil widely used in
      Brazilian cuisine and traditional medicine. Pregnant Wistar female rats were used
      in this study for three treatment groups (250, 500 and 1000 mg/kg/day) and a
      control group. The OPCB was administered orally throughout the period of
      organogenesis of females (6th until the 15th day of gestation). The pregnant
      females were gross necropsied on d20, followed by maternal and fetus examination,
      to evaluate the teratogenicity, reproductive and developmental performance of
      OPCB. The results showed there was no significant statistical difference in the
      ponderal evolution of the pregnant females, as well as in the behavioral,
      hematological, biochemical or histopathological data, indicating the absence of
      maternal toxicity of the oil. The mean number of corpora lutea, implantation and
      resorption sites, as well as all calculated reproductive rates, also remained
      statistically similar between the groups, indicating low embryotoxic effects of
      the tested plant specie. In fetal examination, external anomalies and skeletal
      abnormalities were observed in all treated and control groups. The NOAEL for
      maternal toxicity and embryo/fetal development for the OPCB administered by
      gavage, was 1000 mg/kg/bw/day.

PMID- 29032168
TI  - Ineffectiveness of the Tobacco Hazards Prevention Act in patients with severe and
      persistent mental illness.
AB  - OBJECTIVES: The effect of the Tobacco Hazards Prevention Act (THPA) on the
      reduction of tobacco use in the general population in Taiwan is understood.
      However, there has been little research on how these policies affect people with
      severe and persistent mental illness (SPMI). Hence, the influence of the THPA on
      daily cigarette use by patients with SPMI was investigated in a 3-year follow-up.
      The risk and protective factors in smoking behavior and cessation were
      investigated. STUDY DESIGN: This is an observational study. METHODS: A total of
      144 participants (78 of whom had smoked >100 cigarettes throughout their
      lifetime) were randomly selected from a healthcare network. Then, 100 of 144
      patients with SPMI, included 50 smokers and 50 non-smokers, have agreed with 1st
      year follow-up. Eighty-two patients with SPMI, consisted of 44 smokers and 38 non
      smokers, have agreed with 2nd year follow-up. RESULTS: Although women were less
      likely to smoke than men, those who did smoke reduced the number of cigarettes
      less than men over the 3-year period. Less-educated patients were more likely to
      smoke than those who were more educated but reduced the number of daily
      cigarettes more after implementation of the THPA. Maternal overprotection was a
      risk factor and paternal care a protective factor for smoking. Addiction, a
      perception of pleasure, interpersonal relationships, and self-destructive
      behavior increased cigarette smoking. Patients perceived that smoking alleviated
      their depressive symptoms. CONCLUSIONS: The THPA was ineffective for patients
      with SPMI. Some factors had different effects on the development of smoking
      behavior and the cessation process. Understanding the etiology of smoking can
      help policymakers establish more effective programs for smoking prevention and
      cessation.

PMID- 29032170
TI  - Reprint of: Decomposition of PPCPs by ultrasound-assisted advanced Fenton
      reaction: A case study with salicylic acid.
AB  - The study is about the degradation of a widely used pharmaceutical and personal
      care product-salicylic acid by sonocatalysis, and the experimental design of the
      reaction system. The first part of the study consists of sonication (572kHz) in
      the presence of zero-valent iron (ZVI) with or without H2O2 to select and
      optimize the operational parameters as frequency, time, initial solute
      concentration, dose of reagents and pH. The second part consists of the use of
      response surface methodology and multiple regression to develop an experimental
      design modeland to assess the individual and interactive effects of pH, power
      (Po), ZVI dose and H2O2. The results showed that the optimal conditions predicted
      by the model without defining any restrictions are: pH=2.0, Po=120W, ZVI=24mgL-1,
      which provide total salicyclic acid and 48% TOC decay. However, the prediction
      implies intensive consumption of energy and reagents, and must therefore be
      modified by restricting the value of TOC decay to a lower value and that of pH to
      a higher one. Cross-validation tests showed that the prediction accuracy of the
      model was considerably high with 5.0-9.4% deviation from the experimental data.

PMID- 29032171
TI  - Reprint of: State-of-the-art on ultrasonic oil production technique for EOR in
      China.
AB  - Ultrasonic oil production technique for enhanced oil recovery (EOR) attracts more
      attention due to its high adaptability, simple operation, low cost and zero
      pollution to the oil reservoir. In this paper, recent new downhole tools used for
      enhanced oil recovery developed in China are summarized. Furthermore, research
      advance on some key problems that affect the widespread application of ultrasonic
      oil production technique in China are also summarized in view of what are the
      primary factors that influence crude oil paraffin inhibition and viscosity
      reduction, whether ultrasonic excitation is better than chemical agent for any
      plugs removal and whether ultrasound-chemical combination plug removal technology
      has the best plugs removal effect. The purpose of this paper is to provide
      reference for the broad application of ultrasonic oil production for enhance oil
      recovery.

PMID- 29032169
TI  - Survival Advantage of Both Human Hepatocyte Xenografts and Genome-Edited
      Hepatocytes for Treatment of alpha-1 Antitrypsin Deficiency.
AB  - Hepatocytes represent an important target for gene therapy and editing of single
      gene disorders. In alpha-1 antitrypsin (AAT) deficiency, one missense mutation
      results in impaired secretion of AAT. In most patients, lung damage occurs due to
      a lack of AAT-mediated protection of lung elastin from neutrophil elastase. In
      some patients, accumulation of misfolded PiZ mutant AAT protein triggers
      hepatocyte injury, leading to inflammation and cirrhosis. We hypothesized that
      correcting the Z mutant defect in hepatocytes would confer a selective advantage
      for repopulation of hepatocytes within an intact liver. A human PiZ allele was
      crossed onto an immune-deficient (NSG) strain to create a recipient strain (NSG
      PiZ) for human hepatocyte xenotransplantation. Results indicate that NSG-PiZ
      recipients support heightened engraftment of normal human primary hepatocytes as
      compared with NSG recipients. This model can therefore be used to test hepatocyte
      cell therapies for AATD, but more broadly it serves as a simple, highly
      reproducible liver xenograft model. Finally, a promoterless adeno-associated
      virus (AAV) vector, expressing a wild-type AAT and a synthetic miRNA to silence
      the endogenous allele, was integrated into the albumin locus. This gene-editing
      approach leads to a selective advantage of edited hepatocytes, by silencing the
      mutant protein and augmenting normal AAT production, and improvement of the liver
      pathology.

PMID- 29032172
TI  - LPS enhances expression of CD204 through the MAPK/ERK pathway in murine bone
      marrow macrophages.
AB  - BACKGROUND AND AIMS: Lipopolysaccharide (LPS) is a main component of the Gram
      negative bacterial cell wall and is associated with a greater risk of
      atherosclerosis development in periodontal disease. LPS has been reported to
      increase both CD36 and CD204 expression and enhance the uptake of modified low
      density lipoprotein (LDL). However, the signaling pathways by which LPS enhances
      these expression levels and function have not been fully elucidated, although the
      clarification of these signaling pathways is important for identifying
      therapeutic targets for atherosclerosis. METHODS AND RESULTS: We have shown here
      that LPS activated the mitogen-activated protein kinase (MAPK)/extracellular
      signal-regulated kinase (ERK) pathway, increased both CD204 and CD36 expression,
      and enhanced the uptake of acetylated-LDL (Ac-LDL) in mouse bone marrow
      macrophages. The MAPK/ERK kinase (MEK) inhibitors, U0126 (1 MUM) and PD0325901
      (10 nM), did not affect the expression of either CD36 or CD204 or the uptake of
      Ac-LDL under normal conditions (no treatment with LPS). In contrast, U0126 (1
      MUM) and PD0325901 (10 nM) blocked the LPS-induced increase in Ac-LDL uptake and
      CD204 expression but not CD36 expression. CONCLUSIONS: These results suggest that
      LPS may increase Ac-LDL uptake and enhance CD204 expression through MAPK/ERK
      activation and CD36 expression through an ERK-independent pathway. Since MEK
      inhibitors block CD204 expression in mouse BM macrophages only under LPS
      treatment but not under normal conditions, a MEK inhibitor might be a good
      candidate compound for the treatment of LPS-induced atherosclerosis.

PMID- 29032174
TI  - C/EBPalpha and PU.1 exhibit different responses to RANK signaling for
      osteoclastogenesis.
AB  - The transcription factors C/EBPalpha and PU.1 are upregulated by RANKL through
      activation of its receptor RANK during osteoclastogenesis and are critical for
      osteoclast differentiation. Herein we investigated the mechanisms underlying how
      C/EBPalpha and PU.1 regulate osteoclast differentiation in response to RANK
      signaling. We showed that C/EBPalpha or PU.1 overexpression could initiate
      osteoclastogenesis and upregulate the expressions of the osteoclast genes
      encoding the nuclear factor of activated T-cells, C1, cathepsin K, and tartrate
      resistant acid phosphatase independently of RANKL. However, while PU.1
      upregulated C/EBPalpha, C/EBPalpha could not upregulate PU.1. RANK has a unique
      cytoplasmic domain, 535IVVY538 motif, which is crucial for osteoclast
      differentiation. We demonstrated that mutational inactivation of RANK IVVY motif
      blocked osteoclast differentiation and significantly attenuated C/EBPalpha, but
      not PU.1, expression, indicating that RANK-IVVY-induced signaling is dispensable
      to PU.1 upregulation during osteoclastogenesis. However, C/EBPalpha or PU.1
      overexpression failed to promote osteoclastogenesis in cells expressing mutated
      RANK IVVY motif. We noted that RANK-IVVY-motif inactivation significantly
      repressed osteoclast genes as compared with a vector control, suggesting that
      IVVY motif might also negatively regulate osteoclast inhibitors during
      osteoclastogenesis. Consistently, IVVY-motif inactivation triggered upregulation
      of RBP-J, a potent osteoclast inhibitor, during osteoclastogenesis. Notably,
      C/EBPalpha or PU.1 overexpression in cells expressing mutated RANK IVVY motif
      failed to control the deregulated RBP-J expression, resulting in repression of
      osteoclast genes. Accordingly, RBP-J silencing in the mutant cells rescued
      osteoclastogenesis with C/EBPalpha or PU.1 overexpression. In conclusion, we
      revealed that while PU.1 and C/EBPalpha are critical for osteoclastogenesis, they
      respond differently to RANKL-induced activation of RANK IVVY motif.

PMID- 29032176
TI  - Three-dimensional evaluation of marginal and internal fit of 3D-printed interim
      restorations fabricated on different finish line designs.
AB  - PurposeTo evaluate the influence of fabrication method and finish line design on
      marginal and internal fit of full-coverage interim restorations. MethodsFour
      typodont models of maxillary central-incisor were prepared for full-coverage
      restorations. Four groups were defined; knife-edge (KE), chamfer (C), rounded
      shoulder (RS), rounded-shoulder with bevel (RSB). All preparations were digitally
      scanned. A total of 80 restorations were fabricated; 20 per group (SLA/3D-printed
      n=10, milled n=10). All restorations were positioned on the master die and
      scanned using micro-computed tomography. The mean gaps were measured digitally
      (ImageJ). The results were compared using MANOVA (alpha=.05). ResultsInternal and
      marginal gaps were significantly influenced by fabrication method (P=.000) and
      finish-line design (P=.000). 3D-Printed restorations showed statistically
      significant lower mean gap compared to milled restorations at all points
      (P=.000). The mean internal gap for 3D-printed restorations were 66, 149, 130,
      95MUm and for milled restorations were 89, 177, 185, 154MUm for KE, C, RS, RSB
      respectively. The mean absolute marginal discrepancy in 3D-printed restorations
      were (30, 41, 30, 28MUm) and in milled restorations were (56, 54, 52, 38MUm) for
      KE, C, RS, RSB respectively. ConclusionsThe fabrication methods showed more of an
      influence on the fit compared to the effect of the finish-line design in both
      milled and printed restorations. SLA-printed interim restorations exhibit lower
      marginal and internal gap than milled restorations. Nonetheless, for both
      techniques, all values were within the reported values for CAD/CAM restorations.
      Significance3D-printing can offer an alternative fabrication method comparable to
      those of milled restorations.

PMID- 29032175
TI  - The effect of raloxifene on bone marrow adipose tissue and bone turnover in
      postmenopausal women with osteoporosis.
AB  - In patients with postmenopausal osteoporosis low bone volume is associated with
      high bone marrow adipose tissue (MAT). Moreover, high MAT is associated with
      increased fracture risk. This suggests an interaction between MAT and bone
      turnover, however literature remains equivocal. Estrogen treatment decreases MAT,
      but the effect of raloxifene, a selective estrogen receptor modulator (SERM)
      registered for treatment of postmenopausal osteoporosis, on MAT is not known. The
      aim of this study is 1] to determine the effect of raloxifene on MAT and 2] to
      determine the relationship between MAT and bone turnover in patients with
      osteoporosis. Bone biopsies from the MORE trial were analyzed. The MORE trial
      investigated the effects of raloxifene 60 or 120mg per day versus placebo on bone
      metabolism and fracture incidence in patients with postmenopausal osteoporosis.
      We quantified MAT in iliac crest biopsies obtained at baseline and after 2years
      of treatment (n=53; age 68.2+/-6.2years). Raloxifene did not affect the change in
      MAT volume after 2years compared to baseline (placebo: 1.89+/-10.84%, raloxifene
      60mg: 6.31+/-7.22%, raloxifene 120mg: -0.77+/-10.72%), nor affected change in
      mean adipocyte size (placebo: 1.45 (4.45) MUm, raloxifene 60mg: 1.45 (4.35) MUm,
      raloxifene 120mg: 0.81 (5.21) MUm). Adipocyte number tended to decrease after
      placebo treatment (-9.92 (42.88) cells/mm2) and tended to increase during
      raloxifene 60mg treatment (13.27 (66.14) cells/mm2) while adipocyte number
      remained unchanged in the raloxifene 120mg group, compared to placebo (3.06
      (39.80) cells/mm2, Kruskal-Wallis p=0.055, post hoc: placebo vs raloxifene 60mg
      p=0.017). MAT volume and adipocyte size were negatively associated with
      osteoclast number at baseline (R2=0.123, p=0.006 and R2=0.098, p=0.016
      respectively). Furthermore adipocyte size was negatively associated with osteoid
      surface (R2=0.067, p=0.049). Finally, patients with vertebral fractures had
      higher MAT volume (50.82 (8.80)%) and larger adipocytes (55.75 (3.14) MUm)
      compared to patients without fractures (45.58 (12.72)% p=0.032, 52.77 (3.73) MUm
      p=0.004 respectively). In conclusion, raloxifene did not affect marrow adipose
      tissue, but tended to increase adipocyte number compared to placebo. At baseline
      MAT volume and adipocyte size were associated with bone resorption, and adipocyte
      size was associated with osteoid surface, suggesting an interaction between bone
      marrow adipocytes and bone turnover. In addition, we found that high MAT volume
      and larger adipocyte size are associated with prevalent vertebral fractures in
      postmenopausal women with osteoporosis, indicating that adipocyte size affects
      bone quality independent of bone volume.

PMID- 29032173
TI  - The reduced osteogenic potential of Nf1-deficient osteoprogenitors is EGFR
      independent.
AB  - Neurofibromatosis type 1 (NF1) is a common genetic disorder caused by mutations
      in the NF1 gene. Recalcitrant bone healing following fracture (i.e.
      pseudarthrosis) is one of the most problematic skeletal complications associated
      with NF1. The etiology of this condition is still unclear; thus, pharmacological
      options for clinical management are limited. Multiple studies have shown the
      reduced osteogenic potential of Nf1-deficient osteoprogenitors. A recent
      transcriptome profiling investigation revealed that EREG and EGFR, encoding
      epiregulin and its receptor Epidermal Growth Factor Receptor 1, respectively,
      were among the top over-expressed genes in cells of the NF1 pseudarthrosis site.
      Because EGFR stimulation is known to inhibit osteogenic differentiation, we
      hypothesized that increased EREG and EGFR expression in NF1-deficient skeletal
      progenitors may contribute to their reduced osteogenic differentiation potential.
      In this study, we first confirmed via single-cell mRNA sequencing that EREG over
      expression was associated with NF1 second hit somatic mutations in human bone
      cells, whereas Transforming Growth Factor beta 1 (TGFbeta1) expression was
      unchanged. Second, using ex-vivo recombined Nf1-deficient mouse bone marrow
      stromal cells (mBMSCs), we show that this molecular signature is conserved
      between mice and humans, and that epiregulin generated by these cells is
      overexpressed and active, whereas soluble TGFbeta1 expression and activity are
      not affected. However, blocking either epiregulin function or EGFR signaling by
      EGFR1 or pan EGFR inhibition (using AG-1478 and Poziotinib respectively) did not
      correct the differentiation defect of Nf1-deficient mBMSCs, as measured by the
      expression of Alpl, Ibsp and alkaline phosphatase activity. These results suggest
      that clinically available drugs aimed at inhibiting EGFR signaling are unlikely
      to have a significant benefit for the management of bone non-union in children
      with NF1 PA.

PMID- 29032177
TI  - Exercise assessment and training in cystic fibrosis: Can less achieve more?

PMID- 29032178
TI  - IgG avidity to Pseudomonas aeruginosa over the course of chronic lung biofilm
      infection in cystic fibrosis.
AB  - BACKGROUND AND OBJECTIVES: The mechanisms leading to low effectiveness of the
      humoral immune response against P. aeruginosa in cystic fibrosis (CF) are poorly
      understood. The aim of the present study was to assess the avidity maturation of
      specific antipseudomonal IgG before and during the development of chronic lung
      infection in a cohort of Danish CF patients. METHODS: Avidity maturation was
      assessed against a pooled P. aeruginosa antigen (St-Ag) and against P. aeruginosa
      alginate in 10 CF patients who developed chronic lung infection and 10 patients
      who developed intermittent lung colonization, using an ELISA technique with the
      thiocyanate elution method. Avidity was quantitatively determined by calculating
      the avidity Constant (Kav). RESULTS: IgG avidity to St-Ag significantly increased
      at the onset (Median Kav=2.47) and one year after the onset of chronic infection
      (Median Kav=3.27), but did not significantly changed in patients who developed
      intermittent colonization. IgG avidity against alginate did not significantly
      change over the years neither in patients who developed chronic lung infection
      (Median Kav=3.84 at the onset of chronic infection), nor in patients who
      developed intermittent colonization. CONCLUSION: IgG avidity to P. aeruginosa
      alginate does not significantly enhance as chronic lung infection progresses.
      This probably plays a role in the difficulty to mount an effective
      opsonophagocytic killing to clear mucoid P. aeruginosa infection in CF.

PMID- 29032179
TI  - Corrigendum to "Does current reporting of lung function by the UK cystic fibrosis
      registry allow a fair comparison of adult centres?" [J Cyst Fibros (2017) 585
      591].

PMID- 29032182
TI  - Catalpol suppresses osteosarcoma cell proliferation through blocking epithelial
      mesenchymal transition (EMT) and inducing apoptosis.
AB  - Catalpol, an iridoid glucoside compound, is reported to possess diverse
      pharmacological actions. However, its effects on osteosarcoma are little to be
      known. In the present study, we showed that catalpol could strongly suppress
      osteosarcoma progression. Catalpol dose-dependently reduced the cancer cell
      viability. The migration of osteosarcoma cells was also consistently suppressed
      by catalpol treatment using the wound healing and transwell migration analysis.
      Catalpol reduced the expressions of Kras, receptor for activated C-kinase
      1(RACK1) and matrix metalloproteinase (MMP)-2 in a dose-dependent manner,
      revealing the blockage of migration. Moreover, both intrinsic and extrinsic
      apoptosis were triggered by catalpol, as evidenced by improved cleaved Caspase-8/
      9/-3 and Poly-(ADP-ribose) polymerase (PARP). Release of Cyto-c in cytoplasm and
      Bax up-regulation in total cells were observed in catalpol-treated cells, while
      mitochondrial Cyto-c and cellular Bcl-2 were down-regulated by catalpol. Reactive
      oxygen species (ROS) production was also involved in catalpol-induced cell death.
      Further, ROS scavenger, N-acetylcysteine (NAC), impeded catalpol-caused
      apoptosis. And suppression of signal transducer and activator of transcription
      3/Janus kinase 2 gene/Src (STAT3/JAK2/Src) was involved in catalpol-induced cell
      death. In vivo, catalpol showed effective ability to reduce the tumor growth. Our
      results illustrated that catalpol might be considered as a promising
      pharmacological agent to suppress osteosarcoma.

PMID- 29032181
TI  - The structure-activity relationship of ginsenosides on hypoxia-reoxygenation
      induced apoptosis of cardiomyocytes.
AB  - Ginsenosides have been studied extensively in recent years due to their
      therapeutic effects in cardiovascular diseases. While most studies examined the
      different ginsenosides individually, few studies compare the therapeutic effects
      among the different types. This study examined how effective protopanaxadiol,
      protopanaxatriol ginsenosides Rh2, Rg3, Rh1, and Rg2 of the ginsenoside family
      are in protecting H9c2 cardiomyocytes from damage caused by
      hypoxia/reoxygenation. In the current study, a model of myocardial ischemia and
      reperfusion was induced in H9c2 cardiomyocytes by oxygen deprivation via a
      hypoxia chamber followed by reoxygenation. Our data show that structures similar
      to that of protopanaxadiol, which lacked the hydroxide group at C6, were more
      effective in lowering apoptosis than structures similar to protopanaxatriol with
      a hydroxide group at C6. As the compounds increased in size and complexity, the
      cardioprotective effects diminished. In addition, the S enantiomer proved to be
      more effective in cardioprotection than the R enantiomer. Furthermore, the
      immunoblotting analysis demonstrated that ginsenosides activate AMPK but suppress
      JNK signaling pathways during hypoxia/reoxygenation. Thus, ginsenosides treatment
      attenuated hypoxia/reoxygenation-induced apoptosis via modulating
      cardioprotective AMPK and inflammation-related JNK signaling pathways.

PMID- 29032183
TI  - Peroxiredoxin-1 of macrophage is critical for mycobacterial infection and is
      controlled by early secretory antigenic target protein through the activation of
      p38 MAPK.
AB  - Early secretory antigenic target protein (ESAT-6) is an important virulent factor
      which plays a crucial role in Mycobacterium tuberculosis (MTB) pathogenesis.
      Here, we demonstrate the role of ESAT-6 in phagocytosis and intracellular
      survival of mycobacteria through a mechanism mediated by regulation of a host
      protein; Peroxiredoxin-1 (Prdx-1). Prdx-1 is an anti-apoptotic and stress
      response protein which protects cells from damage by ROS and H2O2. The J774 A.1
      cells infected with MTB or over-expressing ESAT-6 through eukaryotic promoter
      vector showed elevated expression of Prdx-1. Further investigation revealed that
      the up-regulation of Prdx-1 is mediated through the activation of one of the MAP
      kinases, p38. The NRF-2, a transcriptional activator of Prdx-1 is translocated to
      the nucleus upon phosphorylation by p38 and subsequently, regulates expression of
      Prdx-1. Inhibition of the p38 MAPK by a specific inhibitor, SB203580, abrogates
      the ESAT-6 mediated induction of Prdx-1 expression as well as the phosphorylation
      of NRF-2 in a time-dependent manner. The inhibition of Prdx-1 expression by
      specific siRNA in J774 A.1 cells resulted in the reduced bacterial uptake and
      intracellular survival of the mycobacteria. This is the first report proclaiming
      that the ESAT-6 regulates Prdx-1 which is involved in the increase of
      mycobacterial uptake and survival. The intermediate mechanisms involve the
      increased Prdx-1 production in macrophages through the activation of p38 and NRF
      2 dependent signaling.

PMID- 29032180
TI  - Genomic analysis of Isometamidium Chloride resistance in Trypanosoma congolense.
AB  - Isometamidium Chloride (ISM) is one of the principal drugs used to counteract
      Trypanosoma congolense infection in livestock, both as a prophylactic as well as
      a curative treatment. However, numerous cases of ISM resistance have been
      reported in different African regions, representing a significant constraint in
      the battle against Animal African Trypanosomiasis. In order to identify genetic
      signatures associated with ISM resistance in T. congolense, the sensitive strain
      MSOROM7 was selected for induction of ISM resistance in a murine host.
      Administered ISM concentrations in immune-suppressed mice were gradually
      increased from 0.001 mg/kg to 1 mg/kg, the maximal dose used in livestock. As a
      result, three independent MSOROM7 lines acquired full resistance to this
      concentration after five months of induction, and retained this full resistant
      phenotype following a six months period without drug pressure. In contrast,
      parasites did not acquire ISM resistance in immune-competent animals, even after
      more than two years under ISM pressure, suggesting that the development of full
      ISM resistance is strongly enhanced when the host immune response is compromised.
      Genomic analyses comparing the ISM resistant lines with the parental sensitive
      line identified shifts in read depth at heterozygous loci in genes coding for
      different transporters and transmembrane products, and several of these shifts
      were also found within natural ISM resistant isolates. These findings suggested
      that the transport and accumulation of ISM inside the resistant parasites may be
      modified, which was confirmed by flow cytometry and ex vivo ISM uptake assays
      that showed a decrease in the accumulation of ISM in the resistant parasites.

PMID- 29032184
TI  - Exploring young adult perspectives on the use of gamification and social media in
      a smartphone platform for improving vegetable intake.
AB  - Young adults are the poorest consumers of vegetables. Social media and
      smartphones are frequently used by this demographic and could serve as an
      engaging medium for nutrition promotion. Five focus groups were conducted to
      capture participants' perceptions of a theory-based gamified self-monitoring app
      for improving vegetable intake of young adults. Ranking activities were used to
      gather feedback on preferences for social media posts. Data arising from group
      discussion were analysed using NVivo software using a deductive approach to group
      common ideas into themes. Thirty two participants (14 males) attended (mean age
      23.1 (SD 2.7) years). Qualitative analyses of open discussion revealed two major
      themes regarding preferred features for a smartphone app; (1) the use of visual
      guides for estimating quantities of vegetables and tracking progress, and (2) a
      simple interface. Gamification strategies such as earning badges were viewed more
      positively than the use of a self-reward framework. Social media posts which
      presented food pictures and recipes were ranked most motivating, while awareness
      raising posts received lower scores. Participants indicated a preference for
      viewing but reluctance to post information onto social media. "Just in time"
      situational cues were ranked highly and the use of an "authoritative" tone was
      preferred and associated with credibility. Young adults also ranked messages
      containing "Gen Y" language highly, with a preference for those which were
      personally relevant. The proposed use of social media and mobile-gaming was seen
      as an acceptable approach for improving vegetable intake. Materials should be
      visually appealing, simply designed, credible, and personally relevant to appeal
      to this population. This feedback may inform future mobile-phone based
      interventions targeting improved nutrition in young adults.

PMID- 29032185
TI  - The moderating effects of acculturation on the relation of parenting strategies
      to unhealthy weight control behaviors in Hispanic daughters.
AB  - There is a dearth of research regarding the association of child and parent
      traits to the use of unhealthy weight control behaviors among minority girls with
      obesity. This study examined the moderating effects of mothers' and daughters'
      acculturation in the relation of parenting strategies (setting limits, monitoring
      and discipline) to unhealthy weight control behaviors in Hispanic girls with
      obesity. Participants included 148 Hispanic mother-daughter dyads (Mage = 39.1,
      SD = 6.4 years; Mage = 11.3, SD = 1.5 years, respectively). Two-thirds of the
      mothers were born in Mexico and 46% of them reported low levels of acculturation.
      In contrast, almost all daughters (90%) were born in the United States and
      reported high levels of acculturation. Participants were recruited through school
      nurses and social agencies community coordinators. Mothers and daughters
      completed surveys on demographic, acculturation, unhealthy weight control
      behaviors (daughters only) and parenting strategies (mothers only), and had their
      height, weight, and adiposity assessed. Results from a hierarchical regression
      analysis revealed that daughters' acculturation, but not mothers' acculturation,
      moderated the relation of parenting limit setting to daughters' reported
      engagement in unhealthy weight control behaviors (beta = 1.12, p = 0.007). That
      is, mothers who used more limit setting were less likely to have daughters
      engaging in unhealthy weight control behavior and this association was stronger
      among low acculturated girls than among their highly acculturated counterparts.
      Future research should assess cultural influences and parenting practices in a
      sample of Hispanic mothers and their adolescent daughters of varied weight
      statuses and acculturation levels.

PMID- 29032186
TI  - Does parental substance use always engender risk for children? Comparing
      incidence rate ratios of abusive and neglectful behaviors across substance use
      behavior patterns.
AB  - Parental substance use disorder (SUD) is associated with an added risk for child
      abuse and neglect, but less is understood about how a range of parental use
      behaviors is associated with differential maltreatment frequencies. This study
      used the National Survey of Child and Adolescent Well-Being (NSCAW I) to create
      categories for parental substance use behaviors that are conceptually associated
      with varying levels of substance-related impairments. The study sample was
      composed of 2100 parents of children ages 2-17 years from Wave 4 data collection.
      Weighted negative binomial regression models assessed the relationship between
      substance use behavior patterns and maltreatment frequencies by type. Behavior
      patterns defined by some form of past year substance use were associated with a
      higher frequency of physical or emotional abuse compared to non-users. In
      contrast, only past year SUD was associated with a higher frequency of neglect
      compared to other categories. In sum, the relationship between substance use and
      maltreatment frequencies differed for abuse and neglect, suggesting different
      pathways may be underlying these observed relationships.

PMID- 29032187
TI  - Agonistic antibodies in systemic sclerosis.
AB  - Systemic sclerosis (SSc) is characterized by microangiopathy, excessive fibrosis,
      and the presence of circulating autoantibodies to several cellular and
      extracellular components. The role of autoimmunity in generating the clinical and
      pathologic phenotypes in SSc has been long debated and is still matter of
      controversy. Distinct specificities of antinuclear antibodies (ANAs) are
      selectively detected in SSc patients and are associated with unique disease
      manifestations, but do not have a proven pathogenic role. A new group of
      autoantibodies reactive with cell surface receptors have been identified in SSc
      patients. They have been shown to directly activate pathways that may contribute
      to tissue and vascular damage. As such, they are proposed to have a role as
      agonistic autoantibodies in SSc. According to Koch's third postulate, the
      autoantibodies in question should cause disease when introduced into a healthy
      subject. Therefore, our review will focus on those autoantibodies for which
      agonistic activity has already been demonstrated not only in vitro, but, at least
      partly, also in vivo. These include the antibodies anti-endothelial cells (AECA),
      anti-Platelet-Derived Growth Factor Receptor (PDGFR), anti-Angiotensin II type 1
      receptor (AT1R) and anti-endothelin-1 type A receptor (ETaR). In this review, we
      will discuss also a class of antagonistic autoantibodies, the anti-muscarinic-3
      receptor (M3R) antibodies, since they seem to fulfill the aforementioned
      requirements.

PMID- 29032188
TI  - Genito-urinary genomics and emerging biomarkers for immunomodulatory cancer
      treatment.
AB  - Immunotherapy is gradually becoming a key factor in the therapeutic algorithm for
      patients with genito-urinary (GU) cancers at different stages of disease. Robust
      and reliable biomarkers are crucial for an appropriate inclusion of patients in
      clinical trials and for a reliable patient selection for treatments with
      immunomodulatory drugs. The increasing knowledge on the genomic landscape of GU
      cancers supports stratification of patients for targeted therapies. This review
      focusses on emerging biomarkers and the role of genomics in predicting clinical
      benefit to immunomodulatory agents in GU cancers. Based on cancer incidences and
      available data we restricted this overview to bladder, prostate and renal cancer.

PMID- 29032189
TI  - Laser-evoked potentials in painful radiculopathy.
AB  - OBJECTIVE: The aims of this exploratory study were (1) to develop a standardized
      objective electrophysiological technique with laser-evoked potentials to assess
      dorsal root damage quantitatively and (2) to correlate these LEP measures with
      clinical parameters and sensory abnormalities (QST) in the affected dermatome.
      METHODS: Thirty-eight patients with painful radiculopathy and 20 healthy subjects
      were investigated with LEP recorded from the affected dermatome and control areas
      as well as with quantitative sensory testing. Questionnaires evaluating severity
      and functionality were applied. RESULTS: On average, LEP amplitudes and latencies
      from the affected dermatomes did not differ from the contralateral control side.
      In patients with left L5 radiculopathy (more severely affected) the N2 latency
      was longer and the amplitudes reduced. CONCLUSIONS: The N2P2 amplitude correlated
      with pinprick evoked sensations in QST. The N2 latency from the affected
      dermatome correlates with pain intensity, chronicity, clinical severity and with
      a decrease of physical function. SIGNIFICANCE: An increase in N2-latency
      indicates a more pronounced nerve root damage, which is associated with a
      decrease of function and an increase of severity and pain. LEP amplitudes are
      associated with the functional status of the nociceptive system and may
      distinguish between degeneration of neuronal systems and central sensitization
      processes.

PMID- 29032190
TI  - Transient increase in sAPPalpha secretion in response to Abeta1-42 oligomers: an
      attempt of neuronal self-defense?
AB  - Amyloid precursor protein (APP), a key molecule of Alzheimer disease, is
      metabolized in 2 antagonist pathways generating the soluble APP alpha (sAPPalpha)
      having neuroprotective properties and the beta amyloid (Abeta) peptide at the
      origin of neurotoxic oligomers, particularly Abeta1-42. Whether extracellular
      Abeta1-42 oligomers modulate the formation and secretion of sAPPalpha is not
      known. We report here that the addition of Abeta1-42 oligomers to primary
      cortical neurons induced a transient increase in alpha-secretase activity and
      secreted sAPPalpha 6-9 hours later. Preventing the generation of sAPPalpha by
      using small interfering RNAs (siRNAs) for the alpha-secretases ADAM10 and ADAM17
      or for APP led to increased Abeta1-42 oligomer-induced cell death after 24 hours.
      Neuronal injuries due to oxidative stress or growth factor deprivation also
      generated sAPPalpha 7 hours later. Finally, acute injection of Abeta1-42
      oligomers into wild-type mouse hippocampi induced transient secretion of
      sAPPalpha 48-72 hours later. Altogether, these data suggest that neurons respond
      to stress by generating sAPPalpha for their survival. These data must be taken
      into account when interpreting sAPPalpha levels as a biomarker in neurological
      disorders.

PMID- 29032192
TI  - Age-dependent association of thyroid function with brain morphology and
      microstructural organization: evidence from brain imaging.
AB  - Thyroid hormone (TH) is crucial during neurodevelopment, but high levels of TH
      have been linked to neurodegenerative disorders. No data on the association of
      thyroid function with brain imaging in the general population are available. We
      therefore investigated the association of thyroid-stimulating hormone and free
      thyroxine (FT4) with magnetic resonance imaging (MRI)-derived total intracranial
      volume, brain tissue volumes, and diffusion tensor imaging measures of white
      matter microstructure in 4683 dementia- and stroke-free participants (mean age
      60.2, range 45.6-89.9 years). Higher FT4 levels were associated with larger total
      intracranial volumes (beta = 6.73 mL, 95% confidence interval = 2.94-9.80).
      Higher FT4 levels were also associated with larger total brain and white matter
      volumes in younger individuals, but with smaller total brain and white matter
      volume in older individuals (p-interaction 0.02). There was a similar interaction
      by age for the association of FT4 with mean diffusivity on diffusion tensor
      imaging (p-interaction 0.026). These results are in line with differential
      effects of TH during neurodevelopmental and neurodegenerative processes and can
      improve the understanding of the role of thyroid function in neurodegenerative
      disorders.

PMID- 29032191
TI  - Aging and a genetic KIBRA polymorphism interactively affect feedback- and
      observation-based probabilistic classification learning.
AB  - Probabilistic category learning involves complex interactions between the
      hippocampus and striatum that may depend on whether acquisition occurs via
      feedback or observation. Little is known about how healthy aging affects these
      processes. We tested whether age-related behavioral differences in probabilistic
      category learning from feedback or observation depend on a genetic factor known
      to influence individual differences in hippocampal function, the KIBRA gene
      (single nucleotide polymorphism rs17070145). Results showed comparable age
      related performance impairments in observational as well as feedback-based
      learning. Moreover, genetic analyses indicated an age-related interactive effect
      of KIBRA on learning: among older adults, the beneficial T-allele was positively
      associated with learning from feedback, but negatively with learning from
      observation. In younger adults, no effects of KIBRA were found. Our results add
      behavioral genetic evidence to emerging data showing age-related differences in
      how neural resources relate to memory functions, namely that hippocampal and
      striatal contributions to probabilistic category learning may vary with age. Our
      findings highlight the effects genetic factors can have on differential age
      related decline of different memory functions.

PMID- 29032193
TI  - Selenium-functionalized liposomes for systemic delivery of doxorubicin with
      enhanced pharmacokinetics and anticancer effect.
AB  - Liposomes have shown to be an excellent drug delivery system, but the short in
      vivo fate discourages their popularity. This work aimed to develop selenium
      functionalized liposomes (SeLPs) for doxorubicin (Dox) delivery to prolong the
      systemic circulation of liposomes by in situ selenium coating and enhance the
      anticancer effect via the synergy between Dox and selenium. Dox-loaded SeLPs (Dox
      SeLPs) were prepared by film hydration/active loading/in situ reduction technique
      and characterized by particle size, entrapment efficiency and morphology. The
      resulting Dox-SeLPs were 127 nm around in particle size (uncoated liposomes 107
      nm) and were spherical in morphology. It was shown that Dox-SeLPs possessed a
      sustained release effect for Dox and could increase the cellular uptake of Dox
      compared with Dox-loaded liposomes (Dox-LPs). The accumulative Dox release from
      Dox-SeLPs was 46.5% and it was 64.9% for Dox-LPs within 84 h. Moreover, Dox-SeLPs
      exhibited slower drug release in the fetal bovine serum. Trafficking pathway
      study revealed that clathrin-mediated endocytosis and macropinocytosis were
      involved in the cellular uptake process of Dox-SeLPs. The in vitro cytotoxicity
      and apoptosis test indicated that Dox-SeLPs had higher cytotoxicity than that of
      free Dox and Dox-LPs. Dox-SeLPs showed a IC50 of 0.92 +/- 0.16 MUg/mL on A549
      cells, far lower than that of free Dox (4.40 +/- 0.58 MUg/mL) and Dox-LPs (5.68
      +/- 0.73 MUg/mL). Dox-SeLPs significantly improved the pharmacokinetic property
      and enhanced the antitumor efficacy of Dox in tumor-bearing mice. In conclusion,
      SeLPs exhibit good sustained release for Dox and have synergic anticancer effect
      with Dox, which may be promising as drug delivery vehicle.

PMID- 29032194
TI  - In situ mucoadhesive-thermosensitive liposomal gel as a novel vehicle for nasal
      extended delivery of opiorphin.
AB  - Previous studies proved the effectiveness of an intravenous PEGylated liposomal
      formulation of opiorphin (1mg/mL) in protecting the drug from enzymatic
      degradation, and improving intensity and duration of its painkilling effect.
      Therefore, considering the advantages of nasal administration, the aim of this
      work was the development of a liposomal mucoadhesive thermo-sensitive in situ gel
      for the extended nasal delivery of opiorphin. With this purpose, the potential of
      a series of combinations of different polymers (i.e. chitosan,
      hydroxypropylmethylcellulose, Poloxamer, Carbopol) in forming solutions able to
      rapidly gel at the nasal cavity temperature (34  degrees C) has been
      investigated. The best formulations were further characterized for gel strength
      and mucoadhesion properties. The selected formulation, composed by Poloxamer 407
      (26.5%) and Carbopol 934P (1%), showed short gelation time at 34  degrees C (10s)
      and suitable mucoadhesion duration (5.5h) and strength (27g/cm2). Due to the low
      volume administrable via the nasal route, a concentrated liposomal formulation of
      the peptide (16.5mg/mL) was developed and loaded in the selected in situ gel
      formulation. Ex-vivo permeation studies, by excised nasal porcine mucosa, showed
      that the liposomal hydrogel formulation enabled a sustained and controlled
      delivery of opiorphin over more than 5h, and highlighted the role of the
      liposomal carrier in enhancing up to 6 times permeability coefficient and
      permeation rate of the peptide through the lipophilic nasal mucosa compared to a
      free peptide-loaded gel.

PMID- 29032196
TI  - Global causes of vision loss in 2015: are we on track to achieve the Vision 2020
      target?

PMID- 29032197
TI  - Interleukin-22 attenuates double-stranded RNA-induced upregulation of PD-L1 in
      airway epithelial cells via a STAT3-dependent mechanism.
AB  - Double-stranded RNA derived from viruses induces host immune responses. PD-L1,
      also known as B7-H1, is an immune-checkpoint molecule associated with the escape
      of viruses from host immune systems, which plays a role in the persistence of
      viral infection, resulting in exacerbations of underlying diseases such as asthma
      and chronic obstructive pulmonary disease. Interleukin (IL)-22 is produced from
      various immune cells and has protective properties on mucosal tissue. The binding
      of IL-22 to IL-22 receptor induces STAT3 activation. We investigated the effect
      of IL-22 on the expression in airway epithelial cells in vitro and in mouse lungs
      in vivo after the stimulation with an analog of viral double-stranded RNA,
      polyinosinic-polycytidylic acid (poly I:C). Stimulation with poly I:C upregulated
      PD-L1 expression on BEAS-2B cells. This upregulation of PD-L1 was attenuated by
      IL-22 administration. STAT3 phosphorylation was induced by IL-22 and poly I:C.
      Treatment of cells with STAT3 siRNA abolished the effect of IL-22 on the poly I:C
      induced upregulation of PD-L1. This upregulation of PD-L1 was also attenuated by
      IL-11, a cytokine inducing STAT3 phosphorylation, in BEAS-2B cells. In mouse lung
      cells in vivo, IL-22 suppressed poly I:C-induced upregulation of PD-L1. These
      results suggest that IL-22 attenuates virus-induced upregulation of PD-L1 in
      airway epithelial cells via a STAT3-dependent mechanism.

PMID- 29032198
TI  - Antagonism of cysteinyl leukot-riene receptor 1 (cysLT1R) by montelukast
      regulates differentiation of MC3T3-E1 cells under overloaded mechanical
      environment.
AB  - Long-term exposure to overloaded mechanical environment induces bone fatigue
      damage symptoms and osteoblast damages. Montelukast is a selective cysteinyl
      leukot-riene receptor 1 (cysLT1R) antagonist, which has been used for the
      treatment of bronchial asthma in clinics. In the current study, we have
      identified a novel pharmacological role of montelukast by finding that it has
      protective properties against overload damage in osteoblastic MC3T3-E1 cells.
      Firstly, our results show that CysLT1R is expressed in MC3T3-E1 cells. Mechanical
      tensile strain of 5000-7000 MUepsilon resulted in a significant upregulation of
      CysLT1R in osteoblastic MC3T3-E1 cells in an intensity dependent manner.
      Secondly, MTT assay indicates that loading with 5000 MUepsilon mechanical strain
      inhibited cell proliferation, which was suppressed by montelukast treatment.
      Furthermore, montelukast promotes cell differentiation by increasing the
      expression of ALP and RUNX2. Alizarin Red S staining assay showed that
      montelukast abolished the inhibitory effects of overload mechanics on osteoblast
      mineralization. Mechanistically, the effect of montelukast on osteoblastic
      differentiation acted by activating the extracellular regulated protein kinases
      (ERK) pathway. The obtained results suggested that montelukast promotes
      proliferation and differentiation in osteoblasts exposed to overload mechanics.

PMID- 29032195
TI  - Global causes of blindness and distance vision impairment 1990-2020: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Contemporary data for causes of vision impairment and blindness form
      an important basis of recommendations in public health policies. Refreshment of
      the Global Vision Database with recently published data sources permitted
      modelling of cause of vision loss data from 1990 to 2015, further disaggregation
      by cause, and forecasts to 2020. METHODS: In this systematic review and meta
      analysis, we analysed published and unpublished population-based data for the
      causes of vision impairment and blindness from 1980 to 2014. We identified
      population-based studies published before July 8, 2014, by searching online
      databases with no language restrictions (MEDLINE from Jan 1, 1946, and Embase
      from Jan 1, 1974, and the WHO Library Database). We fitted a series of regression
      models to estimate the proportion of moderate or severe vision impairment
      (defined as presenting visual acuity of <6/18 but >=3/60 in the better eye) and
      blindness (presenting visual acuity of <3/60 in the better eye) by cause, age,
      region, and year. FINDINGS: We identified 288 studies of 3 983 541 participants
      contributing data from 98 countries. Among the global population with moderate or
      severe vision impairment in 2015 (216.6 million [80% uncertainty interval 98.5
      million to 359.1 million]), the leading causes were uncorrected refractive error
      (116.3 million [49.4 million to 202.1 million]), cataract (52.6 million [18.2
      million to 109.6 million]), age-related macular degeneration (8.4 million [0.9
      million to 29.5 million]), glaucoma (4.0 million [0.6 million to 13.3 million]),
      and diabetic retinopathy (2.6 million [0.2 million to 9.9 million]). Among the
      global population who were blind in 2015 (36.0 million [12.9 million to 65.4
      million]), the leading causes were cataract (12.6 million [3.4 million to 28.7
      million]), uncorrected refractive error (7.4 million [2.4 million to 14.8
      million]), and glaucoma (2.9 million [0.4 million to 9.9 million]). By 2020,
      among the global population with moderate or severe vision impairment (237.1
      million [101.5 million to 399.0 million]), the number of people affected by
      uncorrected refractive error is anticipated to rise to 127.7 million (51.0
      million to 225.3 million), by cataract to 57.1 million (17.9 million to 124.1
      million), by age-related macular degeneration to 8.8 million (0.8 million to 32.1
      million), by glaucoma to 4.5 million (0.5 million to 15.4 million), and by
      diabetic retinopathy to 3.2 million (0.2 million to 12.9 million). By 2020, among
      the global population who are blind (38.5 million [13.2 million to 70.9
      million]), the number of patients blind because of cataract is anticipated to
      rise to 13.4 million (3.3 million to 31.6 million), because of uncorrected
      refractive error to 8.0 million (2.5 million to 16.3 million), and because of
      glaucoma to 3.2 million (0.4 million to 11.0 million). Cataract and uncorrected
      refractive error combined contributed to 55% of blindness and 77% of vision
      impairment in adults aged 50 years and older in 2015. World regions varied
      markedly in the causes of blindness and vision impairment in this age group, with
      a low prevalence of cataract (<22% for blindness and 14.1-15.9% for vision
      impairment) and a high prevalence of age-related macular degeneration (>14% of
      blindness) as causes in the high-income subregions. Blindness and vision
      impairment at all ages in 2015 due to diabetic retinopathy (odds ratio 2.52 [1.48
      3.73]) and cataract (1.21 [1.17-1.25]) were more common among women than among
      men, whereas blindness and vision impairment due to glaucoma (0.71 [0.57-0.86])
      and corneal opacity (0.54 [0.43-0.66]) were more common among men than among
      women, with no sex difference related to age-related macular degeneration (0.91
      [0.70-1.14]). INTERPRETATION: The number of people affected by the common causes
      of vision loss has increased substantially as the population increases and ages.
      Preventable vision loss due to cataract (reversible with surgery) and refractive
      error (reversible with spectacle correction) continue to cause most cases of
      blindness and moderate or severe vision impairment in adults aged 50 years and
      older. A large scale-up of eye care provision to cope with the increasing numbers
      is needed to address avoidable vision loss. FUNDING: Brien Holden Vision
      Institute.

PMID- 29032199
TI  - Affinity and path of binding xylopyranose unto E. coli xylose permease.
AB  - Glucose transporters (GLUTs), expressed in all types of human cells, are
      responsible for the uptake of sugars as the primary energy source for the normal
      functions of good cells and for the abnormal growth of cancer cells. The E. coli
      xylose permease (XylE), a homologue of human GLUTs, has been investigated more
      thoroughly than other major facilitator proteins in the current literature. In
      this paper, we present a molecular dynamics (MD) study of an all-atom model
      system to elucidate the atomistic details and the free-energy landscape along the
      path of binding a xylopyranose (XYP) from the extracellular space to the inside
      of the transporter protein XylE. From the MD simulations, the Gibbs free energy
      of binding was found to be -4.4kcal/mol in agreement with the experimental value
      of -4.7kcal/mol. The accuracy of our study is further shown in the computed
      hydration energy of XYP of -14.6kcal/mol in comparison with the experimental data
      of -15.0kcal/mol. Along the binding path, the Gibbs free energy of the XYP-XylE
      complex first rises from zero in the dissociated state to approximately 4
      kcal/mol in the transition state (when XylE slightly increases its opening toward
      the extracellular side to accommodate XYP) before dropping down to -9.0 kcal/mol
      in the bound state. These quantitative insights indicate the fast equilibration
      between the bound and the unbound states of XylE and XYP. They also serve as an
      atomistic-dynamic corroboration of the experimental conclusion that XylE is a
      high-affinity sugar transporter.

PMID- 29032200
TI  - Sez6l2 regulates phosphorylation of ADD and neuritogenesis.
AB  - Increasing evidence shows that immune-mediated mechanisms may contribute to the
      pathogenesis of central nervous system disorders including cerebellar ataxias, as
      indicated by the aberrant production of neuronal surface antibodies. We
      previously reported a patient with cerebellar ataxia associated with production
      of a new anti-neuronal antibody, anti-seizure-related 6 homolog like 2 (Sez6l2).
      Sez6l2 is a type 1 membrane protein that is highly expressed in the hippocampus
      and cerebellar cortex and mice lacking Sez6l2 protein family members develop
      ataxia. Here we used a proteomics-based approach to show that serum derived from
      this patient recognizes the extracellular domain of Sez6l2 and that Sez6l2
      protein binds to both adducin (ADD) and glutamate receptor 1 (GluR1). Our results
      indicate that Sez6l2 is one of the auxiliary subunits of the AMPA receptor and
      acts as a scaffolding protein to link GluR1 to ADD. Furthermore, Sez6l2
      overexpression upregulates ADD phosphorylation, whereas siRNA-mediated
      downregulation of Sez612 prevents ADD phosphorylation, suggesting that Sez6l2
      modulates AMPA-ADD signal transduction.

PMID- 29032201
TI  - KLHL7 promotes TUT1 ubiquitination associated with nucleolar integrity:
      Implications for retinitis pigmentosa.
AB  - Kelch-like protein 7 (KLHL7) is a component of Cul3-based Cullin-RING ubiquitin
      ligase. Recent studies have revealed that mutations in klhl7 gene cause several
      disorders, such as retinitis pigmentosa (RP). Although KLHL7 is considered to be
      crucial for regulating the protein homeostasis, little is known about its
      biological functions. In this study, we report that KLHL7 increases terminal
      uridylyl transferase 1 (TUT1) ubiquitination involved in nucleolar integrity.
      TUT1 is normally localized in nucleolus; however, expression of KLHL7 facilitates
      a vulnerability of nucleolar integrity, followed by a decrease of TUT1
      localization in nucleolus. On the other hand, pathogenic KLHL7 mutants, which
      causes an onset of RP, have little effect on both nucleolar integrity and TUT1
      localization. Finally, KLHL7 increases TUT1 ubiquitination levels. Taken
      together, these results imply that KLHL7 is a novel regulator of nucleolus
      associated with TUT1 ubiquitination. Our study may provide a valuable information
      to elucidate a pathogenic mechanism of RP.

PMID- 29032202
TI  - PACT is required for MDA5-mediated immunoresponses triggered by Cardiovirus
      infection via interaction with LGP2.
AB  - Laboratory of genetics and physiology 2 (LGP2) and melanoma differentiation
      associated gene 5 (MDA5) cooperatively detect viral RNA in the cytoplasm of
      Cardiovirus-infected cells and activate innate immune responses. Here, we
      evaluated whether the double-stranded RNA-binding protein PACT plays a role in
      this anti-viral response to further elucidate the mechanism. Immunoprecipitation
      experiments demonstrated that PACT interacts with LGP2 and that this interaction
      is enhanced by encephalomyocarditis virus (EMCV) infection. In vitro interaction
      analyses using purified recombinant proteins confirmed that the single-stranded
      Theiler's murine encephalitis virus genome enhanced the interaction between LGP2
      and PACT. Small interfering RNA knockdown experiments further indicated that PACT
      is required for Cardiovirus-triggered interferon responses. To support this
      functional interaction with LGP2, overexpressed PACT was shown to enhance EMCV
      triggered interferon promoter activity only when LGP2 and MDA5 were co-expressed
      but not when MDA5 is expressed alone. Together, our findings indicate a possible
      role of PACT in regulating the Cardiovirus-triggered immune responses mediated by
      MDA5 and LGP2, which opens the door to novel therapeutic strategies in interferon
      related autoimmune diseases and cancer.

PMID- 29032203
TI  - Construction of artificial human peritoneal tissue by cell-accumulation technique
      and its application for visualizing morphological dynamics of cancer peritoneal
      metastasis.
AB  - Human peritoneum is composed of mesothelial monolayer and stromal tissue
      containing microvasculature. Dissemination and infiltration of cancer cells to
      the peritoneum result in cancer peritoneal metastasis which is an important
      prognostic factor of intraperitoneal or intrapelvic carcinoma. To elucidate an
      initial metastatic mechanism of cancer cells, in vitro human peritoneal models
      are demanded. In this study, we created a three-dimensional artificial human
      peritoneal tissue (AHPT) harboring the blood or lymphatic vascular network by
      cell-accumulation technique. Morphological analysis demonstrated that AHPT had
      mesothelial monolayer with polygonal flat cells with apical microvilli, and
      stroma-like structure containing fibroblasts surrounded by extracellular matrix
      and blood or lymphatic vascular network. To assess AHPT as a tool for cancer
      peritoneal metastasis model, colon and ovarian cancer cells (HT-29 and SKOV3)
      were seeded onto AHPT. HT-29 cells showed poor metastatic characteristics forming
      thick clusters in mesothelial layer without invasion into stroma-like structure.
      On the other hand, SKOV3 cells rapidly invaded intercellular spaces between
      mesothelial cells and then spread over the stroma-like structure accompanying
      lymphatic invasion, showing aggressive metastatic characteristics. These results
      demonstrated that the metastatic dynamics of cancer cells with different
      characteristics are able to visualized by AHPT, suggesting that this tissue can
      be a powerful tool for the basic research of cancer peritoneal dissemination and
      metastasis.

PMID- 29032204
TI  - Angtensin II elicits a cAMP-dependent intestinal anion secretion by stimulating
      PGE2 release through AT1 subtype receptors in rat ileum.
AB  - A growing literature has demonstrated that the renin-angiotensin system (RAS)
      involves in gut function. Angiotensin II (AngII) stimulates Cl- secretion in
      intestine epithelial cells. However, the underlying signal pathway remains
      unexplored. Here, we explored that serosal application of Ang II (5 * 10-8 M)
      significantly increased the baseline Isc compared to the control group in rat
      ileum. Tetrodotoxin (TTX) failed to suppress Isc evoked by Ang II. However, the
      Ang II-evoked Isc was significantly suppressed by the ATR1 antagonist losartan
      instead of ATR2 antagonist PD123319. Of interest, both cyclooxygenase (COX)-1
      inhibitor SC560 and COX-2 specific inhibitor ns398 blocked the Ang II-evoked Isc.
      Preincubation of submucosa/mucosa preparations with Ang II for 10 min
      significantly increased PGE2 production, which was abolished by either COX-1 or
      COX-2 inhibitor. In addition, the Ang II-induced PGE2 release was also attenuated
      by ATR1 receptor antagonist rather than selective ATR2 receptor antagonist.
      Furthermore, preincubation of tissues for 15 min with forskolin, a cAMP
      activator, markedly blocked the Isc evoked by AngII, while intracellular Ca2+
      pump inhibitor thapsigargin, L-type Ca2+ channel blocker nicadipine or the
      epithelial Na+ channel blocker amiloride didn't show such function. These results
      suggest that Ang II evokes cAMP-activated intestinal anion secretion by
      stimulating PGE2 release through activation of ATR1.

PMID- 29032205
TI  - Binding and Hydrolysis of a Single ATP Is Sufficient for N-Gate Closure and DNA
      Supercoiling by Gyrase.
AB  - Topoisomerases catalyze the relaxation, supercoiling, catenation, and
      decatenation of DNA. Gyrase is a bacterial topoisomerase that introduces negative
      supercoils into DNA in an ATP-dependent reaction. The enzyme consists of two GyrB
      subunits, containing the ATPase domains, and two GyrA subunits. Nucleotide
      binding to gyrase B GyrB causes closing of the N-gate in gyrase, which orients
      bound DNA for supercoiling. N-gate re-opening after ATP hydrolysis, at the end of
      the supercoiling reaction, resets the enzyme for subsequent catalytic cycles.
      Gyrase binds and hydrolyzes two ATP molecules per catalytic cycle. Here, we
      dissect the role of these two binding and hydrolysis events using gyrase with one
      ATP-binding- and hydrolysis-deficient subunit, or with one binding-competent, but
      hydrolysis-deficient ATPase domain. We show that binding of a single ATP molecule
      induces N-gate closure. Gyrase that can only bind and hydrolyze a single ATP
      undergoes opening and closing of the N-gate in synchrony with ATP hydrolysis, and
      promotes DNA supercoiling under catalytic conditions. In contrast, gyrase that
      can bind two ATP molecules, but hydrolyzes only one, only supercoils DNA under
      stoichiometric conditions. Here, ATP bound to the hydrolysis-deficient subunit
      keeps the N-gate closed after hydrolysis of the other ATP and prevents further
      turnovers. Gyrase with only one functional ATPase domain hydrolyzes ATP with a
      similar rate to wild-type, but its supercoiling efficiency is reduced. Binding
      and hydrolysis of the second ATP may thus ensure efficient coupling of the
      nucleotide cycle with the supercoiling reaction by stabilizing the closed N-gate
      and by acting as a timer for N-gate re-opening.

PMID- 29032206
TI  - Divalent copper complexes as influenza A M2 inhibitors.
AB  - New M2 blockers effective against the ubiquitous amantadine-resistant S31N M2
      mutation in influenza A are needed. Six copper complexes, 2, 4, 6, 8, 9, and 10,
      were synthesized and found to block both wild type and S31N M2. Free Cu2+ also
      blocks M2 S31N but not S31N/H37A. The copper complexes do not block M2 H37A
      (either S31 or S31N). The complexes were effective against three influenza A
      strains in cell-culture assays, but less toxic to cells than CuCl2. For example
      4, Cu(cyclooctylamineiminodiacetate), which was stable at pH > 4 in the buffers
      used, had an EC50 against A/Calif/07/2009 H1N1 of 0.7 +/- 0.1 MUM with a CC50 of
      147 MUM (therapeutic index, averaged over three strains, 67.8). In contrast,
      CuCl2 had an EC50 of 3.8 +/- 0.9 MUM and CC50 of 19 MUM. Because M2 H37 is highly
      conserved, these complexes show promise for further testing as drugs against all
      strains of influenza A.

PMID- 29032207
TI  - The effect of unsuccessful retrieval on children's subsequent learning.
AB  - It is well known that successful retrieval enhances subsequent adults' learning
      by promoting long-term retention. Recent research has also found benefits from
      unsuccessful retrieval, but the evidence is not as clear-cut when the
      participants are children. In this study, we employed a methodology based on
      guessing-the weak associate paradigm-to test whether children can learn from
      generated errors or whether errors are harmful for learning. We tested second-
      and third-grade children in Experiment 1 and tested preschool and kindergarten
      children in Experiment 2. With slight differences in the method, in both
      experiments children heard the experimenter saying one word (cue) and were asked
      to guess an associate word (guess condition) or to listen to the correspondent
      target-associated word (study condition), followed by corrective feedback in both
      conditions. At the end of the guessing phase, the children undertook a cued
      recall task in which they were presented with each cue and were asked to say the
      corrected target. Together, the results showed that older children-those in
      kindergarten and early elementary school-benefited from unsuccessful retrieval.
      Older children showed more correct responses and fewer errors in the guess
      condition. In contrast, preschoolers produced similar levels of correct and error
      responses in the two conditions. In conclusion, generating errors seems to be
      beneficial for future learning of children older than 5years.

PMID- 29032208
TI  - Chitosan-based nano-formulation enhances the anticancer efficacy of hesperetin.
AB  - Cancer is one of the major causes of increased morbidity and mortality in modern
      society. Colorectal cancer is the third leading cause for cancer related death
      worldwide. Current chemotherapeutics are not very effective and have severe side
      effects. Hesperetin is a bioflavonoid from citrus fruits and its clinical use is
      restricted because of the poor water solubility. Folate receptor is overexpressed
      in various cancer cells. Therefore, we synthesized the chitosan folate hesperetin
      nanoparticle (CFH) by covalently conjugating folic acid with chitosan molecules.
      The size of the CFH nanoparticles is around 450nm, which is advantageous for
      passively targeting the cancer cell specifically due to the leaky vasculature of
      the tumour. Particle surface and size were observed using SEM and TEM studies.
      The results show that hesperetin has an IC50 value of 190MUM and it induces
      apoptosis in HCT15 cells, however, CFH is very potent in inhibiting the
      proliferation with the IC50 value of 28MUM. In addition, CFH inhibited colony
      formation and induced apoptosis by regulating the expression of proapoptotic
      genes expression. Therefore, the chitosan - folic acid conjugation appears to be
      the suitable carrier for colorectal cancer cell-specific delivery of hesperetin.

PMID- 29032209
TI  - Customizing the spent coffee for Trichoderma reesei cellulase immobilization by
      modification with activating agents.
AB  - This study has explored the possibility to reuse the waste, spent coffee material
      for the cellulase enzyme immobilization. By the coffee surface modification with
      different activating agents, it was attempted to develop the convenient method
      for creation of a capable porous carrier for this purpose. Among the most common
      activating agents, glutaraldehyde, chlorine dioxide and hydrogen peroxide
      provided the most acceptable choice for the coffee surface modification. The
      changes that occurred on the coffee surface due to agents' treatment exposure
      were recorded by using of the FTIR spectra and SEM micrographs. The highest
      immobilization yield (55%) and immobilization efficiency (45%) were attained
      during 30min of the treatment time, by employing of 30% chlorine dioxide aqueous
      solution within 6mL/g activator/carrier ratio. The kinetic process was found to
      be predicted by the pseudo-second-order model. The cellulase immobilization onto
      the coffee surface provides an excellent base for increasing the enzyme
      availability to the substrate and enhancing the enzyme productivity, by offering
      the new perspectives to the industrial sector.

PMID- 29032210
TI  - Chemical composition of Cyclocarya paliurus polysaccharide and inflammatory
      effects in lipopolysaccharide-stimulated RAW264.7 macrophage.
AB  - This study was designed to study the chemical composition of Cyclocarya paliurus
      polysaccharide and inflammatory effects in lipopolysaccharide (LPS)-stimulated
      RAW264.7 macrophage. A new elution (0.3% NaCl aqueous solution) of Cyclocarya
      paliurus polysaccharide (CPP-3) was characterized by different methods such as
      fourier transform infrared spectra (FT-IR), UV-vis, gas chromatography-mass
      spectrometry (GC-MS), high performance gel chromatography (HPGLC) and scanning
      electron microscopy (SEM). Cell viability was measured by MTT test, phagocytosis
      assay was measured by Neutral red uptake assay, nitrite was measured by Griess
      assay, TNF-alpha and IL-1beta analysis were measured by ELISA, PGE2 was measured
      by enzyme immunoassay system. The results showed that CPP-3 was comprised of two
      polysaccharides with average molecular weight (Mw) of 5.69*104Da and 4.94*103Da.
      CPP-3 contains six monosaccharides, of which are rhamnose (Rha), arabinose (Ara),
      xylose (Xyl), mannose (Man), glucose (Glu), galactose (Gal), the molar ratio of
      six monosaccharides is 0.060:0.109:0.053:0.128:0.293:0.357. CPP-3 increased the
      amount of NO released from mouse macrophage RAW264.7 and significantly increased
      the levels of TNF-alpha, IL-1beta and PGE2 (P<0.01). CPP-3 suppressed LPS
      stimulated RAW264.7 macrophage to release NO, TNF-alpha, IL-1beta and PGE2
      (P<0.01). CPP-3 and LPS accounted for synergistic effect on the release of NO and
      TNF-alpha, CPP-3 and LPS accounted for antagonistic effect on the release of IL
      1beta and PGE2.

PMID- 29032211
TI  - Discrete SeNPs-Macromolecule Binding Manipulated by Hydrophilic Interaction.
AB  - Nanoparticle-protein conjugates are promising probes for biological diagnostics
      and versatile building blocks for nanotechnology. Here we demonstrate the
      interaction of SeNPs with BSA macromolecule simply by physical adsorption method.
      The interaction between SeNPs and BSA has been investigated by UV-Vis,
      fluorescence, circular dichroism (CD) spectroscopic and thermal methods. The
      esterase-like activity of BSA towards PNPA was investigated in the presence of
      SeNPs. The effects of SeNPs on the stability and conformational changes of BSA
      were studied, which indicated that the binding of SeNPs with BSA induced relative
      changes in secondary structure of protein. SeNPs acted as a structure stabilizer
      for BSA which was further confirmed by thermal denaturation study. The
      hydrophilic bonding forces played important roles in the BSA-SeNPs complex
      formation. The putative binding site of SeNPs on BSA was near to Sudlow's site
      II. The hydrophilic interaction of SeNPs on the stability and structure of BSA
      would find promising application in drug delivery system.

PMID- 29032212
TI  - An acidic heteropolysaccharide from Mesona chinensis: Rheological properties,
      gelling behavior and texture characteristics.
AB  - Polysaccharide from Mesona chinensis is becoming increasingly attractive focus
      because of its gelling property and biological activities. In this study, the
      rheological properties of an acidic heteropolysaccharide from Mesona chinensis
      (MCP) were investigated in dilute and semidilute solutions. Dynamic rheology was
      systematically conducted to investigate the effects of concentration,
      temperature, pH values, salts and freeze-thaw variations on the rheological
      properties of MCP. Results showed that the rheological properties of MCP
      exhibited pseudoplastic characteristic and "gel-like" behavior by the flow
      behavior detection. A closed hysteresis loop was formed when the MCP
      concentration reached 4%, and the Gel was generated when the MCP concentration
      reached 5%. The storage modulu (G') and loss modulu (G") of MCP solution were
      increased with increasing oscillation frequency at concentration of 4% and 5%.
      The phase angel (tandelta) was less than 1, indicating MCP was a weak gel in
      linear viscoelastic region. The gel exhibited favourable textural properties when
      MCP at concentration 5%. The scanning electron microscope (SEM) verified MCP had
      a unique lotus leaf-like shape with some small irregular round-like rods surface
      morphology.

PMID- 29032213
TI  - Deproteinised natural rubber latex grafted poly(dimethylaminoethyl methacrylate) 
      poly(vinyl alcohol) blend membranes: Synthesis, properties and application.
AB  - Natural rubber latex was initially deproteinised (DNRL) and then subjected to
      physicochemical modifications to make high functional membranes for drug delivery
      applications. Initially, DNRL was prepared by incubating with urea,
      sodiumdodecylsulphate and acetone followed by centrifugation. The
      deproteinisation was confirmed by CHN analysis. The DNRL was then chemically
      modified by grafting (dimethylaminoethyl methacrylate) onto NR particles by using
      a redox initiator system viz; cumene hydroperoxide/tetraethylenepentamine,
      followed by dialysis for purification. The grafting was confirmed by dynamic
      light scattering, Fourier transform infrared spectroscopy and nuclear magnetic
      resonance spectroscopy. The grafted system was blended with a hydrophilic
      adhesive polymer PVA and casted into membranes. The membranes after blending
      showed enhanced mechanical properties with a threshold concentration of PVA. The
      moisture uptake, swelling and water contact angle experiments indicated an
      increased hydrophilicity with an increased PVA content in the blend membranes.
      The grafted DNRL possessed significant antibacterial property which has been
      found to be retained in the blended form. A notable decrease in cytotoxicity was
      observed for the modified DNRL membranes than the bare DNRL membranes. The in
      vitro drug release studies using rhodamine B as a model drug, confirmed the
      utility of the prepared membranes to function as a drug delivery matrix.

PMID- 29032214
TI  - High surface area mesoporous activated carbon-alginate beads for efficient
      removal of methylene blue.
AB  - High surface area mesoporous activated carbon-alginate (AC-alginate) beads were
      successfully synthesized by entrapping activated carbon powder derived from
      Mangosteen fruit peel into calcium-alginate beads for methylene blue (MB) removal
      from aqueous solution. The structure and surface characteristics of AC-alginate
      beads were analyzed using Fourier transform infra-red (FTIR) spectroscopy,
      scanning electron microscopy (SEM) and surface area analysis (SBET), while
      thermal properties were tested using thermogravimetric analysis (TGA). The effect
      of AC-alginate dose, pH of solution, contact time, initial concentration of MB
      solution and temperature on MB removal was elucidated. The results showed that
      the maximum adsorption capacity of 230mg/g was achieved for 100mg/L of MB
      solution at pH 9.5 and temperature 25 degrees C. Furthermore, the adsorption of
      MB on AC-alginate beads followed well pseudo-second order equation and
      equilibrium adsorption data were better fitted by the Freundlich isotherm model.
      The findings reveal the feasibility of AC-alginate beads composite to be used as
      a potential and low cost adsorbent for removal of cationic dyes.

PMID- 29032215
TI  - Determining mushroom tyrosinase inhibition by imidazolium ionic liquids: A
      spectroscopic and molecular docking study.
AB  - The inhibition effects of imidazolium ionic liquids (ILs) on the enzyme kinetics
      of mushroom tyrosinase is reported. A simple UV-VIS spectrophotometric assay was
      used to measure the reaction kinetics of the reaction between mushroom tyrosinase
      and L-dopa. Seven different imidazolium ILs, comprised of 1-alkyl-3
      methylimidazolium ([Imn1+], n=2, 4, 6) cations paired with several anions that
      included Cl-, [NO3-], methanesulfonate ([MeSO3-]), trifluoromethanesulfonate (or
      triflate, [TFMS-]), and bis(trifluoromethylsulfonyl)imide ([Tf2N-]). Lineweaver
      Burk plots were generated from the recovered kcat and Km parameters using four to
      six substrate concentrations per measurement. The results show that mushroom
      tyrosinase activity was consistently inhibited by all of the ILs and that the
      type of inhibition was non-competitive in nearly all cases. Only the data for
      [Im21+][Tf2N-] suggested that the inhibition mechanism was competitive with the
      substrate. Molecular docking simulations were performed using AutoDock4.2 and
      AutoDock Vina and revealed that all cations docked in the L-dopa active site.
      Anions showed varied results that included locations both within and outside of
      the active site.

PMID- 29032216
TI  - Gelatin - Oxidized carboxymethyl cellulose blend based tubular electrospun
      scaffold for vascular tissue engineering.
AB  - The present work deals with the fabrication of electrospun tubular scaffold based
      on in-situ crosslinked blend of gelatin - oxidized carboxymethyl cellulose (OCMC)
      for vascular tissue engineering. The flow behavior and spinability of the
      hydrogel despite the in-situ crosslinked gelatin chains evaluated by Raman
      spectroscopic studies and rheological studies was utilized for electrospinning.
      The study highlights the tunable pore size and fiber diameter of the nanofibers
      with the manipulation of electrospinning parameters. With a future perspective of
      vascular tissue engineering, the electrospinning parameters yielding smooth bead
      free fibers and maximum magnitude in pore size and fiber diameter as well their
      homogenous distribution were selected for the fabrication of tubular constructs
      which is rarely reported. The surface and mechanical properties were evaluated to
      validate its properties to the native vessel. Biocompatibility was studied in
      vitro with BALB/c 3T3 cells and in vivo after subcutaneous implantation in rats.
      MTT assay confirmed its no-toxicity and no abnormal foreign body reaction were
      observed by 7 and 15days after implantation. Crosslinking with biocompatible
      crosslinker OCMC has rendered insolubility to gelatin yet making it spinable for
      electrospinning to fabricate porous, nanofibrous vascular biomaterial.

PMID- 29032217
TI  - Preoperative Prediction of the Necessity for Anterior Clinoidectomy During
      Microsurgical Clipping of Ruptured Posterior Communicating Artery Aneurysms.
AB  - BACKGROUND: Although most posterior communicating artery (PCoA) aneurysms can be
      clipped easily with excellent results, some require anterior clinoidectomy for
      safe and complete clipping. OBJECTIVE: To review our microsurgical series of
      ruptured PCoA aneurysms and identify the preoperative predictors for anterior
      clinoidectomy during microsurgical clipping for PCoA aneurysms. METHODS: Results
      from microsurgical clipping of 104 patients with ruptured PCoA aneurysms were
      reviewed retrospectively. Distances and angles were obtained from computed
      tomographic angiography and compared between the anterior and nonanterior
      clinoidectomy groups. RESULTS: Anterior clinoidectomy was required in 19 of the
      104 cases (18%). None developed surgical complications due to anterior clinoid
      process (ACP) resection, including postoperative visual deficit. Univariate and
      multivariate analyses revealed that the distances from the ACP tip to the
      aneurysmal proximal neck and from the ACP line to the aneurysmal proximal neck
      were statistically significant predictive factors for the need of anterior
      clinoidectomy. Based on a receiver operating characteristic analysis, the
      distances from the ACP tip to the aneurysmal proximal neck <4.0 mm and from the
      ACP line to the aneurysmal proximal neck <=2.0 mm were selected as optimal cutoff
      values for predicting the necessity of anterior clinoidectomy, and the area under
      the receiver operating characteristic curve values were 0.991 and 0.955,
      respectively. CONCLUSIONS: In case of ruptured PCoA aneurysm surgery, the
      distances from the ACP tip to the aneurysmal proximal neck and from the ACP line
      to the aneurysmal proximal neck were both found to be useful predictors of
      whether anterior clinoidectomy was required.

PMID- 29032218
TI  - The Hypoglossal Nerve: Anatomical Study of Its Entire Course.
AB  - OBJECTIVE: Only a few anatomic studies of the entire course of the hypoglossal
      nerve (cranial nerve XII) have been reported. We analyzed all relationships of
      the 12th nerve with surrounding structures from the brainstem to the tongue
      through a microscopic perspective. A comprehensive anatomically and clinically
      oriented classification of its different segments is proposed. METHODS: Ten
      formalin-fixed adult human cadaveric heads (20 sides) were dissected with the aim
      to explore the entire course of cranial nerve XII via lateral suboccipital, far
      lateral partial, or total transcondylar routes. Different segments of the nerve
      were identified based on the hypoglossal course and its relationship with
      surrounding structures. Measurements of every portion of the nerve were taken in
      all specimens during dissection. RESULTS: The hypoglossal nerve was divided into
      5 segments: cisternal, intracanalar, descending, horizontal, and ascending.
      Detailed and comprehensive examination of basic anatomic relationships through
      the view of different transcranial and endoscope-assisted approaches was
      performed. A new perspective of the hypoglossal canal is proposed, and the venous
      plexus surrounding the intracanalar segment of the nerve is described in detail.
      CONCLUSIONS: Classification of 5 segments for the hypoglossal nerve seems
      anatomically valid, and it is surgically oriented with respect to all surgical
      approaches. Precise knowledge of the relationships with the surrounding
      structures may help to prevent some complications during surgery, and it is
      useful to explain, segment by segment, the pathogenic mechanisms for nerve
      injuries that are evidenced by lesions that exist along the entire intracranial
      and extracranial course.

PMID- 29032219
TI  - Emergency Extracranial-Intracranial Bypass to Revascularize Salvageable Brain
      Tissue in Acute Ischemic Stroke Patients.
AB  - OBJECTIVE: To present an algorithm based on clinical and radiologic factors,
      including magnetic resonance imaging (MRI) perfusion/diffusion mismatch (PDM),
      for the indication of urgent cerebral bypass in patients with acute ischemic
      stroke. METHODS: Clinical and radiologic data of 8 consecutive patients
      undergoing urgent cerebral revascularization for acute ischemic stroke owing to
      occlusion of internal carotid or middle cerebral artery between 2012 and 2015
      were analyzed. All patients either were ineligible for or failed first-line
      treatment with emergent endovascular revascularization. Indication for urgent
      bypass was based on clinical worsening and MRI PDM, indicating threat for stroke
      extension. Clinical outcome was measured using National Institutes of Health
      Stroke Scale and modified Rankin Scale before and after bypass surgery, at 3
      month follow-up, and at last follow-up. RESULTS: All patients presented with
      clinical worsening after initiation of acute stroke treatment. Cerebral
      revascularization was performed 9.6 hours (SD 9.0) after clinical worsening. All
      patients had preoperative MRI PDM. No bypass complications, such as anastomosis
      failure or postoperative hemorrhage, occurred. MRI diffusion ratio before and
      after bypass was stable or improved in 7 patients and progressed in 1 patient
      without clinical worsening. MRI PDM and perfusion improved in all 4 patients who
      underwent postoperative MRI. Clinical outcome was favorable with a median
      improvement of 7 points on National Institutes of Health Stroke Scale and of 2
      points on modified Rankin Scale at last follow-up. CONCLUSIONS: Based on an
      algorithm indicating salvageable brain tissue, cerebral revascularization can be
      safely performed in an emergency setting in a highly selected group of patients
      with acute ischemic stroke with favorable clinical outcome.

PMID- 29032220
TI  - Electrodiagnostic and Advanced Neuroimaging Characterization for Successful
      Treatment of Spinal Extradural Arachnoid Cyst.
AB  - BACKGROUND: Spinal extradural arachnoid cysts are relatively uncommon. Rarely,
      large cysts presented with spinal cord compression requiring surgical
      intervention. CASE DESCRIPTION: We report a patient with a progressively
      enlarging spinal extradural arachnoid cyst causing worsening right S1
      radiculopathy and gastrocnemius muscle atrophy. Electromyography and nerve
      conduction studies revealed an S1 motor radiculopathy. Serial magnetic resonance
      imaging findings confirmed enlargement of the small cyst originating from the
      sacral thecal sac on the right while 2 smaller cysts on the left remained stable.
      Dynamic computed tomography myelogram revealed connection to the thecal sac
      behind the right S1 nerve root. We performed a right hemilaminectomy from L5 to
      S2, exposed the cyst pedicle ligated it, and marsupialized the cyst. After
      surgery, the patient showed clinical and electrodiagnostic improvement.
      CONCLUSION: This case illustrates the principles of timely surgical intervention
      after advanced diagnostic imaging and electrodiagnostic testing to improve
      neurologic function and minimize complications.

PMID- 29032221
TI  - Spontaneous Fusion of S2/S3 Spondyloptosis in an Adult.
AB  - BACKGROUND: Spondyloptosis is grade V on the Meyerding classification. Traumatic
      spondyloptosis can occur throughout the spinal column, particularly at junctional
      levels, and finding an ideal surgical strategy to address it remains a challenge
      for spinal surgeons. The sacrum is considered a united bone in adults, and sacral
      intersegmental spondyloptosis is extremely rare. CASE REPORT: Herein, we present
      an unusual case of S2/S3 spondyloptosis in a 27-year-old female patient with
      spontaneous solid fusion. CONCLUSIONS: This case demonstrates that similar distal
      sacral pathologies may be managed conservatively when there is no associated
      neurologic deficit, and the osteodiskoligamentous integrity of the
      lumbosacropelvic unit remains intact. Our report plus the very few published
      papers in the literature illustrate the natural history of uncomplicated
      traumatic spondyloptosis and support the role of in situ fusion and
      instrumentation as a reliable alternative to circumferential fusion in patients
      who cannot tolerate staged or prolonged operations.

PMID- 29032222
TI  - Molecular mechanisms of nickel induced neurotoxicity and chemoprevention.
AB  - Nickel (Ni) is widely used in many industrial sectors such as alloy, welding,
      printing inks, electrical and electronics industries. Excessive environmental or
      occupational exposure to Ni may result in tumor, contact dermatitis, as well as
      damages to the nervous system. In recent years, more and more research has
      demonstrated that Ni induced nerve damages are related to mitochondrial
      dysfunction. In this paper, we try to characterize Ni induced neurotoxicity as
      well as the underlying mechanisms, and how to find new drugs for chemoprevention,
      by reviewing chemicals with neuroprotective effects on Ni induced neurotoxicity.

PMID- 29032223
TI  - Glyphosate and Roundup(r) alter morphology and behavior in zebrafish.
AB  - Glyphosate has become the most widely used herbicide in the world, due to the
      wide scale adoption of transgenic glyphosate resistant crops after its
      introduction in 1996. Glyphosate may be used alone, but it is commonly applied as
      an active ingredient of the herbicide Roundup(r). This pesticide contains several
      adjuvants, which may promote an unknown toxicity. The indiscriminate application
      poses numerous problems, both for the health of the applicators and consumers,
      and for the environment, contaminating the soil, water and leading to the death
      of plants and animals. Zebrafish (Danio rerio) is quickly gaining popularity in
      behavioral research, because of physiological similarity to mammals, sensitivity
      to pharmacological factors, robust performance, low cost, short spawning
      intervals, external fertilization, transparency of embryos through larval stages,
      and rapid development. The aim of this study was evaluate the effects of
      glyphosate and Roundup(r) on behavioral and morphological parameters in zebrafish
      larvae and adults. Zebrafish larvae at 3days post-fertilization and adults were
      exposed to glyphosate (0.01, 0.065, and 0.5mg/L) or Roundup(r) (0.01, 0.065, and
      0.5mg/L) for 96h. Immediately after the exposure, we performed the analysis of
      locomotor activity, aversive behavior, and morphology for the larvae and
      exploratory behavior, aggression and inhibitory avoidance memory for adult
      zebrafish. In zebrafish larvae, there were significant differences in the
      locomotor activity and aversive behavior after glyphosate or Roundup(r) exposure
      when compared to the control group. Our findings demonstrated that exposure to
      glyphosate at the concentration of 0.5mg/L, Roundup(r) at 0.065 or 0.5mg/L
      reduced the distance traveled, the mean speed and the line crossings in adult
      zebrafish. A decreased ocular distance was observed for larvae exposed at 0.5mg/L
      of glyphosate. We verified that at 0.5mg/L of Roundup(r)-treated adult zebrafish
      demonstrated a significant impairment in memory. Both glyphosate and Roundup(r)
      reduced aggressive behavior. Our data suggest that there are small differences
      between the effects induced by glyphosate and Roundup(r), altering morphological
      and behavioral parameters in zebrafish, suggesting common mechanisms of toxicity
      and cellular response.

PMID- 29032225
TI  - Right Ventricular Dysfunction in Acute Myocardial Infarction Complicated by
      Cardiogenic Shock: A Hemodynamic Analysis of the Should We Emergently
      Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) Trial and
      Registry.
AB  - BACKGROUND: The prevalence and significance of right ventricular dysfunction
      (RVD) in patients with cardiogenic shock due to acute myocardial infarction (AMI
      CS) have not been well characterized. We hypothesized that RVD is common in AMI
      CS and associated with worse clinical outcomes. METHODS AND RESULTS: We
      retrospectively analyzed patients with available hemodynamics enrolled in the
      Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock
      (SHOCK) trial (n = 139) and registry (n = 258) to identify RVD in AMI-CS. RVD was
      defined by an elevated central venous pressure (CVP), elevated CVP-pulmonary
      capillary wedge pressure (PCWP) ratio, decreased pulmonary artery pulsatility
      index, and decreased right ventricular stroke work index. A P value of <.01 was
      used to infer significance. In the SHOCK trial and registry, respectively, 38%
      and 37% of patients had RVD, but RVD was not associated with 30-day or 6-month
      survival (hazard ratio [HR] 1.51, (99% CI 0.92-2.49; P = .10). RV failure with
      the use of inclusion criteria from the Recover Right Trial for RV Failure (RR
      RVF) requiring percutaneous mechanical circulatory support included elevated CVP
      and CVP/PCWP and a low cardiac index despite >=1 inotrope or vasopressor. In the
      SHOCK trial and registry, respectively, 45% (n = 63/139) and 38% (n = 98/258) of
      patients met RR-RVF criteria. The RR-RVF criteria were not significantly
      associated with 30-day mortality in the registry cohort (HR 1.44, 99% CI 1.01
      2.04; P = .04), or in the trial cohort (HR 1.51, 99% CI 0.92-2.49; P = .10).
      CONCLUSIONS: Hemodynamically defined RVD is common in AMI-CS. Routine assessment
      with pulmonary artery catherization allows detection of RVD; however, further
      work is needed to identify interventions that will result in improved outcomes
      for these patients.

PMID- 29032224
TI  - Limitations of oxygen delivery to cells in culture: An underappreciated problem
      in basic and translational research.
AB  - Molecular oxygen is one of the most important variables in modern cell culture
      systems. Fluctuations in its concentration can affect cell growth,
      differentiation, signaling, and free radical production. In order to maintain
      culture viability, experimental validity, and reproducibility, it is imperative
      that oxygen levels be consistently maintained within physiological "normoxic"
      limits. Use of the term normoxia, however, is not consistent among scientists who
      experiment in cell culture. It is typically used to describe the atmospheric
      conditions of a standard incubator, not the true microenvironment to which the
      cells are exposed. This error may lead to the situation where cells grown in a
      standard "normoxic" oxygen concentration may actually be experiencing a wide
      range of conditions ranging from hyperoxia to near-anoxic conditions at the
      cellular level. This apparent paradox is created by oxygen's sluggish rate of
      diffusion through aqueous medium, and the generally underappreciated effects that
      cell density, media volume, and barometric pressure can have on pericellular
      oxygen concentration in a cell culture system. This review aims to provide an
      overview of this phenomenon we have termed "consumptive oxygen depletion" (COD),
      and includes a basic review of the physics, potential consequences, and
      alternative culture methods currently available to help circumvent this largely
      unrecognized problem.

PMID- 29032226
TI  - Maternal depressive symptoms linked to reduced fecal Immunoglobulin A
      concentrations in infants.
AB  - Secretory Immunoglobulin A (sIgA) plays a critical role to infant gut mucosal
      immunity. Delayed IgA production is associated with greater risk of allergic
      disease. Murine models of stressful events during pregnancy and infancy show
      alterations in gut immunity and microbial composition in offspring, but little is
      known about the stress-microbiome-immunity pathways in humans. We investigated
      differences in infant fecal sIgA concentrations according to the presence of
      maternal depressive symptoms during and after pregnancy. A subsample of 403 term
      infants from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort
      were studied. Their mothers completed the Center of Epidemiologic Studies
      Depression Scale when enrolled prenatally and again postpartum. Quantified by
      Immundiagnostik sIgA ELISA kit, sIgA from infant stool was compared across
      maternal depressive symptom categories using Mann-Whitney U-tests and logistic
      regression models that controlled for various covariates. Twelve percent of women
      reported clinically significant depressive symptoms only prenatally, 8.7% had
      only postpartum symptoms and 9.2% had symptoms both pre and postnatally. Infants
      born to mothers with pre and postnatal symptoms had significantly lower median
      sIgA concentrations than those in the reference group (4.4 mg/g feces vs. 6.3
      mg/g feces; p = 0.033). The odds for sIgA concentrations in the lowest quartile
      was threefold higher (95% CI: 1.25-7.55) when mothers had pre and postnatal
      symptoms, after controlling for breastfeeding status, infant age, antibiotics
      exposure and other covariates. Postnatal symptoms were not associated with fecal
      sIgA, independently of breastfeeding status. Infants born to mothers with
      depressive symptoms appear to have lower fecal sIgA concentrations, predisposing
      them to higher risk for allergic disease.

PMID- 29032227
TI  - Effectiveness of photodynamic therapy associated with irrigants over two biofilm
      models.
AB  - BACKGROUND: This study aimed to evaluate the antibacterial effect and the biofilm
      disruption promoted by antimicrobial photodynamic therapy (aPDT) associated with
      sodium hypochlorite (NaOCl) and chlorexidine (CHX) over monospecies and
      multispecies biofilms. METHODS: In monospecies model, forty-six premolars were
      inoculated with Enterococcus faecalis for 21days and divided into three groups:
      saline, CHX and NaOCl. After irrigation, aPDT was performed. Samples were
      collected at baseline (S1) and after irrigation (S2) and aPDT (S3). Colony
      forming unit (CFU) counts were performed. In multispecies model, sixty bovine
      dentin blocks were infected intraorally for 72h and divided into six groups:
      saline, saline/aPDT, CHX, CHX/aPDT, NaOCl and NaOCl/aPDT. The percentage and the
      biovolume of live cells and the total biovolume were assessed using confocal
      laser scanning microscopy. RESULTS: CHX and NaOCl showed the lowest CFU counts
      (P<0.05). aPDT reduced the bacterial counts in saline (S2-S3; P<0.05). The lowest
      amount of live cells was observed in CHX, CHX/aPDT, NaOCl and NaOCl/aPDT. aPDT
      did not reduce the total biovolume (P>0.05). CONCLUSION: aPDT associated with
      saline reduced the bacterial load in root canals infected with E. faecalis. aPDT
      did not reduce the total biovolume in situ; however, the irrigant was decisive to
      disrupt multispecies biofilms.

PMID- 29032228
TI  - Hidden Malefactor: Occult Foreign Body in Diabetic Foot.

PMID- 29032229
TI  - Sulfonylureas as Initial Treatment for Type 2 Diabetes and the Risk of Severe
      Hypoglycemia.
AB  - PURPOSE: The magnitude of the risk of severe hypoglycemia associated with
      sulfonylureas as the initial treatment for type 2 diabetes in the real-world
      setting is unknown. We assessed the risk of severe hypoglycemia associated with
      initiating monotherapy with sulfonylurea compared with metformin for the
      treatment of type 2 diabetes. METHODS: By using the UK Clinical Practice Research
      Datalink and Hospital Episode Statistics linked to the Office for National
      Statistics, we identified a cohort of patients with type 2 diabetes who initiated
      sulfonylureas or metformin monotherapy between April 1, 1998, and December 31,
      2012, with follow-up until December 31, 2013. Sulfonylurea users were matched one
      to-one to metformin users by high-dimensional propensity scores. Hazard ratios
      (HRs) and 95% confidence intervals (CIs) of severe hypoglycemia, defined as
      requiring hospitalization, were estimated using Cox proportional hazards models
      comparing sulfonylureas with metformin monotherapy. RESULTS: The study cohort
      consisted of 14,012 initiators of sulfonylureas matched to 14,012 initiators of
      metformin. The mean treated follow-up time was 1.41 (standard deviation, 1.84)
      years. Use of sulfonylurea was associated with an elevated incidence of severe
      hypoglycemia compared with metformin as the initiating monotherapy for type 2
      diabetes (incidence rate, 2.4/1000 person-years; 95% CI, 1.90-2.90; HR, 4.53; 95%
      CI, 2.76-7.45). CONCLUSIONS: Sulfonylureas, when prescribed as the initiating
      monotherapy for the treatment of type 2 diabetes, is associated with a 4.5-fold
      increase in the risk of severe hypoglycemia. Given the negative consequences of
      this outcome, clinicians should consider alternative hypoglycemic agents when
      metformin is not tolerated or contraindicated.

PMID- 29032230
TI  - Schistosoma haematobium in Urine Cytology: Diagnosis Is Possible.

PMID- 29032231
TI  - Schistosoma japonicum Presenting as Colon Polyps.

PMID- 29032232
TI  - Incremental Role of 3-Dimensional Echocardiography in Orthostatic Dyspnea.

PMID- 29032233
TI  - Proteome-wide prediction and annotation of mitochondrial and sub-mitochondrial
      proteins by incorporating domain information.
AB  - Mitochondrion is one of the most important subcellular organelle of eukaryotic
      cells. It carries out several biochemical functions that are extremely vital for
      cells. Defects in mitochondria also play an important role in the development and
      progression of different types of cancer. Therefore knowledge of complete
      mitochondrial protein repertoire is essential to understand overall mitochondrial
      functionality, maintenance, dynamics and metabolism. It would be of a great
      practical significance to develop an automated and reliable approach that can
      identify the mitochondrial proteins and their sub-mitochondrial location. In the
      present study, we report a two level prediction method, named as SubMitoPred,
      which predicts mitochondrial proteins (at first level) and their sub
      mitochondrial localization (at second level). Our approach is based on combined
      usage of Pfam domain information and support vector machine model. During
      training we achieved an overall prediction accuracy of 94.37% at first level
      while at the second level a prediction accuracy of 74.91% for inner membrane,
      82.98% for outer membrane, 71.23% for inter-membrane space and 81.58% accuracy
      was achieved for matrix. Evaluation on independent data shows better performance
      of SubMitoPred. Benchmarking showed that SubMitoPred performed better than other
      existing methods. We also annotated human proteome using SubMitoPred. We also
      developed a freely accessible web-server as well as standalone software for the
      use of scientific community, which is available at
      http://proteininformatics.org/mkumar/submitopred/.

PMID- 29032234
TI  - Saccharomyces cerevisiae Mhr1 can bind Xho I-induced mitochondrial DNA double
      strand breaks in vivo.
AB  - Mitochondrial DNA (mtDNA) double-strand break (DSB) repair is essential for
      maintaining mtDNA integrity, but little is known about the proteins involved in
      mtDNA DSB repair. Here, we utilize Saccharomyces cerevisiae as a eukaryotic model
      to identify proteins involved in mtDNA DSB repair. We show that Mhr1, a protein
      known to possess homologous DNA pairing activity in vitro, binds to mtDNA DSBs in
      vivo, indicating its involvement in mtDNA DSB repair. Our data also indicate that
      Yku80, a protein previously implicated in mtDNA DSB repair, does not compete with
      Mhr1 for binding to mtDNA DSBs. In fact, C-terminally tagged Yku80 could not be
      detected in yeast mitochondrial extracts. Therefore, we conclude that Mhr1, but
      not Yku80, is a potential mtDNA DSB repair factor in yeast.

PMID- 29032236
TI  - Renal Trauma in Pediatrics: A Current Review.
AB  - Children are at increased risk of renal injuries from blunt trauma. Four-phase
      computed tomography with intravenous contrast (noncontrast, arterial,
      nephrographic, and pyelographic phases) is the choice for initial imaging,
      although ultrasonography might also be used in children with minimal symptoms.
      The American Association for the Surgery of Trauma developed the known system for
      renal injury grading, which was modified in 2011. The management of pediatric
      renal injuries has largely shifted toward conservative means. However, as long as
      the child remains hemodynamically unstable, renal exploration might be necessary.
      There is a trend toward managing high-grade injuries with interventional
      radiography procedures.

PMID- 29032235
TI  - Variation in Radiologic and Urologic Computed Tomography Interpretation of
      Urinary Tract Stone Burden: Results From the Registry for Stones of the Kidney
      and Ureter.
AB  - OBJECTIVE: To compare the measured stone burden recorded between urologists and
      radiologists, and examine how these differences could potentially impact stone
      management. As current urologic stone surgery guideline recommendations are based
      on stone size, accurate stone measurements are crucial to direct appropriate
      treatment. This study investigated the discrepant interpretation that often
      exists between urologic surgeons and radiologists' estimation of patient urinary
      stone burden. MATERIALS AND METHODS: From November 2015 through August 2016, new
      patients prospectively enrolled into the Registry for Stones of the Kidney and
      Ureter (ReSKU) were included if they had computed tomography images available and
      an accompanying official radiologic report at the time of their urologist
      provider visit. Stone number and aggregate stone size were compared between the
      urologic interpretation and the corresponding radiologic reports. RESULTS: Of 219
      patients who met the inclusion criteria, concordance between urologic and
      radiologic assessment of aggregate stone size was higher for single stone sizing
      (63%) compared with multiple stones (32%). Statistical significance was found in
      comparing the mean difference in aggregate stone size for single and multiple
      stones (P <.01). Over 33% of stone-containing renal units had a radiologic report
      with an unclear size estimation or size discrepancy that could lead to non
      guideline-driven surgical management. CONCLUSION: Significant variation exists
      between urologic and radiologic computed tomography interpretations of stone
      burden. Urologists should personally review patient imaging when considering
      stone surgical management. A standardized method for measuring and reporting
      stone parameters is needed among urologists and radiologists.

PMID- 29032237
TI  - Hospital Charges and Length of Stay Following Radical Cystectomy in the Enhanced
      Recovery After Surgery Era.
AB  - OBJECTIVE: To report our center's experience with enhanced recovery after surgery
      (ERAS) pathway for radical cystectomy (RC), specifically evaluating
      complications, LOS, 30- and 90-day readmissions, and hospital charges. Pathways
      of this type have been shown to decrease the length of stay (LOS) and
      postoperative ileus. However, concerns persist that ERAS is costly and increases
      readmissions. To date, limited studies have evaluated these concerns. MATERIALS
      AND METHODS: Our ERAS protocol was implemented for RC in December 2015. Outcomes
      in ERAS patients were compared with those in RC patients from the time period
      before ERAS. Patients were excluded if they underwent concomitant
      nephroureterectomy. RESULTS: Fifty-six consecutive ERAS patients were compared
      with 54 pre-ERAS patients. The median charge for index hospitalization was
      $31,090 in the ERAS group and $35,489 in the pre-ERAS group (P = .036). The
      median LOS was 5.0 days in the ERAS group and 8.5 days in the pre-ERAS group (P =
      < .001). The pre-ERAS group had a significantly increased use of nasogastric tube
      (13.8% vs 30.0%) and parenteral nutrition (6.9% vs 20.4%). The overall
      complication rate (including infectious, renal, deep vein thrombosis and
      pulmonary embolism, myocardial infarction and stroke, and respiratory and
      gastrointestinal-related complications) was similar between the 2 groups (51.7%
      in the ERAS group and 62.0% in the pre-ERAS group, P = .28). Thirty- and 90-day
      readmissions also remained similar (19.0% vs 14.8%, P = .55, and 31.0% vs 27.7%,
      P = .64). The most common readmission reason was infection, specifically urinary
      tract infection. CONCLUSION: Implementation of the ERAS pathway at our center
      resulted in significantly reduced LOS and total hospital charge, with comparable
      rates of complication and readmission, highlighting the need for ERAS pathways in
      patients undergoing RC.

PMID- 29032238
TI  - Prostate-specific Antigen Density Is a Good Predictor of Upstaging and Upgrading,
      According to the New Grading System: The Keys We Are Seeking May Be Already in
      Our Pocket.
AB  - OBJECTIVE: To analyze the performance of prostate-specific antigen density (PSAD)
      as a predictor of upstaging and prognostic grade group (PGG) upgrading. MATERIALS
      AND METHODS: We retrospectively evaluated data on men with prostate cancer (PCa)
      treated with robot-assisted laparoscopic radical prostatectomy (RALP) at our
      center in 2014-2015. Preoperative PSAD was calculated. Bioptic and pathologic
      PGGs were also considered in the analysis. We defined upgrading as any increase
      in PGG after RALP; upstaging was the pathologic diagnosis of a clinically
      unsuspected stage >=3a PCa. RESULTS: Data on 379 patients were analyzed.
      Upgrading was found in 41.4% of the patients; 29% of the patients were upstaged.
      On multivariable analysis, core involvement and PSAD were found to be predictors
      of upgrading (odds ratio [OR] 1.017, 95% confidence interval [CI] 1.001-1.034, P
      = .039; and OR 3.638, 95% CI 1.084-12.207, P = .001, respectively). Furthermore,
      core involvement and PSAD were predictors of upstaging (OR 1.020, 95% CI 1.020
      1.034, P = .003; and OR 5.656, 95% CI 1.285-24.894, P = .022, respectively). PSAD
      showed areas under the curve of 0.712 (95% CI 0.645-0.780, P = .000) and 0.628
      (95% CI 0.566-0.689, P = .000) for the prediction of upgrading and upstaging,
      respectively. In a subpopulation of 90 patients theoretically eligible for active
      surveillance, 14% were found upstaged and 17% were upgraded. PSAD showed areas
      under the curve of 0.894 (95% CI 0.808-0.97, P = .000) and 0.689 (95% CI 0.539
      0.840, P = .021) for the prediction of upgrading and upstaging, respectively.
      CONCLUSION: PSAD is a valuable predictor of upgrading and upstaging in men with
      PCa who were candidates for surgery and is accurate in selecting patients for AS.

PMID- 29032239
TI  - Outcomes Following Clinical Complete Response to Neoadjuvant Chemotherapy for
      Muscle-invasive Urothelial Carcinoma of the Bladder in Patients Refusing Radical
      Cystectomy.
AB  - OBJECTIVE: To investigate survival outcomes of patients with muscle-invasive
      bladder cancer (MIBC) that demonstrate complete clinical response (cT0) to
      neoadjuvant chemotherapy (NAC) and then reject subsequent radical cystectomy
      (RC). METHODS: A retrospective chart review identified patients with MIBC who
      were cT0 after platinum-based NAC. cT0 was defined as negative cytology,
      cystoscopy with transurethral resection of bladder tumor, and imaging. cT0
      patients refusing for RC were followed up with cytology, cystoscopy with biopsy,
      and cross-sectional imaging. RESULTS: Forty-eight patients were identified with
      MIBC that were cT0 after NAC. Seven patients underwent immediate RC, whereas 41
      elected bladder preservation with close surveillance. Of those remaining 41
      patients, mean age was 68 +/- 11 years with median follow-up of 35 months. NAC
      regimens were 46% methotrexate/vinblastine/doxorubicin/cisplatin, 39%
      gemcitabine/cisplatin, and 15% other platinum-based therapies. Five-year cancer
      specific survival was 87%, disease-free survival was 58%, and cystectomy-free
      survival was 79%. A total of 19 patients (46%) relapsed with 5.4-month median
      recurrence time. CONCLUSION: Bladder preservation may be a reasonable option in a
      highly select subset of patients with MIBC who are complete clinical responders
      after NAC. For those patients that were cT0 after NAC and refused or were
      ineligible for RC, 5-year disease-free survival was nearly 60% and cancer
      specific survival was nearly 90%. Future studies should focus on identifying
      clinical and molecular factors associated with a durable pathologic complete
      response after NAC.

PMID- 29032240
TI  - Natural History and Conservative Treatment Outcomes for Hydroceles: A
      Retrospective Review of One Center's Experience.
AB  - OBJECTIVE: To elucidate epidemiological data and hydrocele progression, we
      reviewed pediatric patients diagnosed with hydroceles in our institution
      retrospectively. MATERIALS AND METHODS: We reviewed data from 355 pediatric
      patients with hydroceles. Questionnaires regarding age at diagnosis, time of
      delivery, presence of hydroceles in the father and brothers, age at recovery, age
      at surgery, cause of hydrocele (if present), type of hydrocele, associated
      pathologies, treatments, and posthydrocelectomy complications were completed by
      reviewing patients' medical records and interviewing their families. RESULTS:
      Patients with congenital hydroceles were more frequently born prematurely (32.5%)
      than were patients with noncongenital hydroceles (15.9%; P = .001). Fathers of 10
      patients (3.7%) and brothers of 21 patients (7.7%) also had hydroceles.
      Hydroceles were associated with inguinal hernias on the same side (12.2%),
      cryptorchidism (7.5%), varicoceles (6.0%), and testis torsion (0.5%). Among
      patients aged >1 year (n = 185), 27 did not undergo operations and healed
      spontaneously at an average of 5.30 +/- 3.36 months. For children aged >1 year
      who did not undergo surgery, the rate of spontaneous recovery within 6 months was
      77.8% and that within 1 year was 96.3%. CONCLUSION: Until strong evidence of
      hydrocele-induced testicular damage in children arises, we recommend following up
      congenital hydroceles until at least 1 year and preferably 2 years of age. We
      recommend following up noncongenital hydroceles for at least 6 months and
      preferably 1 year if there is no associated pathology indicating the need for
      earlier surgery such as an inguinal hernia, cryptorchidism, tense hydrocele,
      testis torsion, or testis mass.

PMID- 29032242
TI  - Combination of vitamin B12 active forms improved fetal growth in Wistar rats
      through up-regulation of placental miR-16 and miR-21 levels.
AB  - AIM: Epidemiological studies have indicated importance of folate and vitamin
      (B12) during pregnancy. Also available evidence on efficacy of B12 forms viz.
      Cyanocobalamin (Cbl), Methylcobalamin (MeCbl), Adenosylcobalamin (AdCbl) and
      Hydroxycobalamin (HCbl) in preventing or treating cobalamin deficiency is
      limited. The present study examines the effect of various forms of B12 in
      combination with folate during pregnancy and their effect on gestational
      outcomes. MAIN METHOD: In the present study, we examined the effect of various
      vitamin B12 forms in presence of recommended folate (RFol: 400MUg/day) and high
      folate (HFol: 5mg/day) on gestational outcomes in female Wistar rats. FINDINGS:
      Dams dosed with excessive folate (HFol group) delivered low birth weight (LBW)
      offsprings (p<0.01) as compared to RFol dams. Plasma homocysteine levels were
      found to be significantly higher (p<0.05) in dams of HFol group and were reduced
      after vitamin B12 supplementation. Excessive folate supplementation and
      homocysteine levels showed inverse association with placental weight (p<0.01) and
      placental efficiency (p<0.05). B12 supplementation significantly up-regulated
      placental miR-16 and miR-21, associated with fetal growth which in turn reflected
      in improved birthweights. Supplementation with vitamin B12 forms, especially
      combination of active forms of cobalamins: MeCbl+AdCbl significantly increased
      birth weights (p<0.05) and modulated gestational outcomes in RFol as well as HFol
      supplemented dams. SIGNIFICANCE: Our results indicated supplementing vitamin B12
      along with folate during pregnancy had positive impact on the gestational
      outcomes. We have shown for the first time that combination of active forms of
      vitamin B12: MeCbl+AdCbl has better efficacy as compared to Cbl, MeCbl, AdCbl and
      HCbl alone.

PMID- 29032243
TI  - DNA methylation patterns are related to co-morbidity status and circulating C
      reactive protein levels in the nursing home elderly.
AB  - Elderly residents of long-term care commonly exhibit a number of age-related
      health deficits, including impaired physical and cognitive function, chronic
      illnesses, and chronic inflammation. Given our previous data relating the
      phenotype and function of innate and adaptive leukocytes from the nursing home
      elderly to chronic conditions and inflammatory biomarkers, we hypothesized that
      these factors would influence the regulatory programming of immune cells, thereby
      contributing to immune dysfunction. Since DNA methylation represents both an
      important regulatory mechanism of cells as well as a biomarker of health and
      disease, we sought to characterize the methylome of peripheral blood mononuclear
      cells (PBMCs) from the nursing home elderly (n=23; 82-98years old, 70% female),
      and compare these patterns to pathological factors such as dementia, co-morbidity
      score and frailty, and immune-related factors such as serum C-reactive protein
      (CRP) and cytokine levels and varicella-zoster virus (VZV) vaccine
      responsiveness. We show that the most significant changes in DNA methylation
      levels occurred in relation to co-morbidity score, including one site, cg07725579
      (FDR-adjusted p<0.05; closest gene, SIRBP2), and nine DNA methylation regions
      (Stouffer's p<0.05). DNA methylation age, although not strongly correlated with
      chronological age, was positively correlated with serum CRP levels (p=0.007), and
      negatively correlated with vaccine responsiveness (p=0.035). To our knowledge,
      this study is one of the first to describe associations of DNA methylation
      patterns with pathological and immune-related factors in residents of long-term
      care, and may provide important clues pertaining to immune cell dysfunction near
      the end of life.

PMID- 29032241
TI  - beta-1,3-Glucan recognition protein 3 activates the prophenoloxidase system in
      response to bacterial infection in Ostrinia furnacalis Guenee.
AB  - Pattern recognition receptors (PRRs) are biosensor proteins that bind to non-self
      pathogen associated molecular patterns (PAMPs). beta-1,3-glucan recognition
      proteins (betaGRPs) play an essential role in immune recognition and signaling
      pathway of insect innate immunity. Here, we report the cloning and
      characterization of cDNA of OfbetaGRP3 from Ostrinia furnacalis larvae. The
      OfbetaGRP3 contains 1455 bp open reading frame, encoding a predicted 484 amino
      acid residue protein. In hemocytes, the expression levels of OfbetaGRP3 in
      Escherichia coli-challenged group were higher than those of Bacillus subtilis
      challenged group at 2, 4, 8, 10 and 12 h post injection (HPI). In fat body,
      OfbetaGRP3 expression in both B. subtilis and E. coli-challenged group was
      significantly higher than that in untreated group from 4 to 10 HPI, and then the
      expression continuously dropped from 12 to 36 HPI. The OfbetaGRP3 expression in
      laminarin-injected group was higher than that in lipopolysaccharides (LPS)
      injected group in various test tissues from 4 to 24 HPI. The LT50 of E. coli
      infected OfbetaGRP3-RNAi larvae (1.0 days) was significantly lower compared with
      that of E. coli infected wild-type larvae (3.0 days) (p < 0.01). Only 10.2%
      Sephadex G50 beads (degree 3) were completely melanized in the larvae inoculated
      with OfbetaGRP3 dsRNA, as compared to 48.8% in control larvae (p < 0.01). A
      notable reduction in the PO activity and IEARase activity in hemolymph was also
      detected in the OfbetaGRP3 knockdown larvae. Our study demonstrates that
      OfbetaGRP3 is one of PRR members involved the PPO-activating system in O.
      furnacalis larvae.

PMID- 29032244
TI  - The impact of SPARC on age-related cardiac dysfunction and fibrosis in
      Drosophila.
AB  - Tissue fibrosis, an accumulation of extracellular matrix proteins such as
      collagen, accompanies cardiac ageing in humans and this is linked to an increased
      risk of cardiac failure. The mechanisms driving age-related tissue fibrosis and
      cardiac dysfunction are unclear, yet clinically important. Drosophila is amenable
      to the study of cardiac ageing as well as collagen deposition; however it is
      unclear whether collagen accumulates in the ageing Drosophila heart. This work
      examined collagen deposition and cardiac function in ageing Drosophila, in the
      context of reduced expression of collagen-interacting protein SPARC (Secreted
      Protein Acidic and Rich in Cysteine) an evolutionarily conserved protein linked
      with fibrosis. Heart function was measured using high frame rate videomicroscopy.
      Collagen deposition was monitored using a fluorescently-tagged collagen IV
      reporter (encoded by the Viking gene) and staining of the cardiac collagen,
      Pericardin. The Drosophila heart accumulated collagen IV and Pericardin as flies
      aged. Associated with this was a decline in cardiac function. SPARC heterozygous
      flies lived longer than controls and showed little to no age-related cardiac
      dysfunction. As flies of both genotypes aged, cardiac levels of collagen IV
      (Viking) and Pericardin increased similarly. Over-expression of SPARC caused
      cardiomyopathy and increased Pericardin deposition. The findings demonstrate
      that, like humans, the Drosophila heart develops a fibrosis-like phenotype as it
      ages. Although having no gross impact on collagen accumulation, reduced SPARC
      expression extended Drosophila lifespan and cardiac health span. It is proposed
      that cardiac fibrosis in humans may develop due to the activation of conserved
      mechanisms and that SPARC may mediate cardiac ageing by mechanisms more subtle
      than gross accumulation of collagen.

PMID- 29032245
TI  - A simple technique investigating baseline heterogeneity helped to eliminate
      potential bias in meta-analyses.
AB  - OBJECTIVES: To perform a worked example of an approach that can be used to
      identify and remove potentially biased trials from meta-analyses via the analysis
      of baseline variables. STUDY DESIGN: True randomisation produces treatment groups
      that differ only by chance; therefore, a meta-analysis of a baseline measurement
      should produce no overall difference and zero heterogeneity. A meta-analysis from
      the British Medical Journal, known to contain significant heterogeneity and
      imbalance in baseline age, was chosen. Meta-analyses of baseline variables were
      performed and trials systematically removed, starting with those with the largest
      t-statistic, until the I2 measure of heterogeneity became 0%, then the outcome
      meta-analysis repeated with only the remaining trials as a sensitivity check.
      CONCLUSION: We argue that heterogeneity in a meta-analysis of baseline variables
      should not exist, and therefore removing trials which contribute to heterogeneity
      from a meta-analysis will produce a more valid result. In our example none of the
      overall outcomes changed when studies contributing to heterogeneity were removed.
      We recommend routine use of this technique, using age and a second baseline
      variable predictive of outcome for the particular study chosen, to help eliminate
      potential bias in meta-analyses.

PMID- 29032247
TI  - Specifications of Targeting Heterochromatin Modifications in Plants.
AB  - Plants encode a diverse repertoire of DNA methyltransferases that have
      specialized to target cytosines for methylation in specific sequence contexts.
      These include the de novo methyltransferase, DOMAINS REARRANGED METHYLTRANSFERASE
      2 (DRM2), which methylates cytosines in all sequence contexts through an RNA
      guided process, the CHROMOMETHYLASES (CMTs), which methylate CHH and CHG
      cytosines (where H is A, T, or C), and METHYLTRANSFERASE 1 (MET1), which
      maintains methylation of symmetrical CG contexts. In this review, we discuss the
      sequence specificities and targeting of each of these pathways. In particular, we
      highlight recent studies that indicate CMTs preferentially target CWG or CWA/CAW
      motifs (where W is A or T), and discuss how self-reinforcing feedback loops
      between DNA methyltransferases and histone modifications characteristic of
      heterochromatin specify targeting. Finally, the initiating events that lead to
      gene body methylation are discussed as a model illustrating how interdependent
      targeting of different silencing pathways can potentiate the establishment of off
      target epialleles.

PMID- 29032246
TI  - Transcriptional regulation of the cyclin-dependent kinase inhibitor,
      p21CIP1/WAF1, by the chelator, Dp44mT.
AB  - BACKGROUND: The cyclin-dependent kinase inhibitor, p21, is well known for its
      role in cell cycle arrest. Novel anti-cancer agents that deplete iron pools
      demonstrate marked anti-tumor activity and are also active in regulating p21
      expression. These agents induce p21 mRNA levels independently of the tumor
      suppressor, p53, and differentially regulate p21 protein expression depending on
      the cell-type. Several chelators, including an analogue of the potent anti-tumor
      agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), have entered
      clinical trials, and thus, their molecular mechanism of action is crucial to
      assess. Hence, this investigation examined how several iron chelators
      transcriptionally regulate p21. METHODS: Promoter-deletion constructs; luciferase
      assays; RT-PCR; western analysis; gene silencing; co-immunoprecipitation.
      RESULTS: The transcriptional regulation of the p21 promoter by iron chelators was
      demonstrated to be dependent on the chelator and cell-type examined. The potent
      anti-cancer chelator, Dp44mT, induced p21 promoter activity in SK-MEL-28 melanoma
      cells, but not in MCF-7 breast cancer cells. Further analysis of the p21 promoter
      identified a 50-bp region between -104 and -56-bp that was required for Dp44mT
      induced activation in SK-MEL-28 cells. This region contained several Sp1-binding
      sites and mutational analysis of this region revealed the Sp1-3-binding site
      played a significant role in Dp44mT-induced activation of p21. Further, co
      immunoprecipitation demonstrated that Dp44mT induced a marked increase in the
      interactions between Sp1 and the transcription factors, estrogen receptor-alpha
      and c-Jun. CONCLUSIONS AND GENERAL SIGNIFICANCE: Dp44mT-induced p21 promoter
      activation via the Sp1-3-binding site and increased Sp1/ER-alpha and Sp1/c-Jun
      complex formation in SK-MEL-28 cells, suggesting these complexes were involved in
      p21 promoter activation.

PMID- 29032249
TI  - High prevalence of sacrococcygeal pilonidal sinus disease in patients with
      ankylosing spondylitis.

PMID- 29032248
TI  - A Critical Role of AMT2;1 in Root-To-Shoot Translocation of Ammonium in
      Arabidopsis.
AB  - Ammonium uptake in plant roots is mediated by AMT/MEP/Rh-type ammonium
      transporters. Out of five AMTs being expressed in Arabidopsis roots, four AMT1
      type transporters contribute to ammonium uptake, whereas no physiological
      function has so far been assigned to the only homolog belonging to the MEP
      subfamily, AMT2;1. Based on the observation that under ammonium supply, the
      transcript levels of AMT2;1 increased and its promoter activity shifted
      preferentially to the pericycle, we assessed the contribution of AMT2;1 to xylem
      loading. When exposed to 15N-labeled ammonium, amt2;1 mutant lines translocated
      less tracer to the shoots and contained less ammonium in the xylem sap. Moreover,
      in an amt1;1 amt1;2 amt1;3 amt2;1 quadruple mutant (qko), co-expression of AMT2;1
      with either AMT1;2 or AMT1;3 significantly enhanced 15N translocation to shoots,
      indicating a cooperative action between AMT2;1 and AMT1 transporters. Under N
      deficiency, proAMT2;1-GFP lines showed enhanced promoter activity predominantly
      in cortical root cells, which coincided with elevated ammonium influx conferred
      by AMT2;1 at millimolar substrate concentrations. Our results indicate that in
      addition to contributing moderately to root uptake in the low-affinity range,
      AMT2;1 functions mainly in root-to-shoot translocation of ammonium, depending on
      its cell-type-specific expression in response to the plant nutritional status and
      to local ammonium gradients.

PMID- 29032250
TI  - Of Mice and Women: A Laparoscopic Mouse Model for Endometriosis.
AB  - STUDY OBJECTIVE: To demonstrate how a novel laparoscopic approach allows the
      development of a mouse model for endometriosis after seeding menstrual
      endometrium from donor mice into the abdominal cavity of syngeneic recipient
      mice. DESIGN: A step-by-step video description of the techniques used to adapt
      the estrous cycle of mice towards a menstrual cycle and to subsequently induce
      endometriosis via laparoscopic seeding of menstrual endometrium. SETTING:
      University research institute. ETHICS: All animal experiments were ethically
      approved by KU Leuven, Belgium (ethical approval number: P031/2013).
      INTERVENTIONS, MEASUREMENTS, AND MAIN RESULTS: Oophorectomized female C57BL/6JRj
      mice received a series of estrogen injections. Next, a progesterone pellet was
      administered, together with a second series of estrogen injections. In addition,
      decidualization of the endometrium was induced with an intrauterine sesame oil
      stimulus. Four days later the progesterone pellet was removed and menstruation
      started [1]. Five hours after the progesterone pellet was removal the uterus was
      harvested, and the menstrual endometrium was dissected and seeded into the
      abdominal cavity of syngeneic recipient mice to induce endometriosis [2] using a
      laparoscopic approach [3]. Uterus and lesions were removed from the recipient
      mice 1 week after induction, and tissues were immunohistochemically stained for
      H&E, vimentin, and cytokeratin. CONCLUSION: In this video we show a novel
      methodology to induce endometriosis in mice using laparoscopic inoculation of
      syngeneic menstrual endometrium, mimicking Sampson's theory of retrograde
      menstruation [4]. Compared with currently available rodent models, our model
      offers a less invasive and more physiologic way for fundamental and preclinical
      endometriosis research, with a high endometriosis incidence and lesion take rate.

PMID- 29032251
TI  - Laparoscopic Isthmocele Repair with Hysteroscopic Assistance.
AB  - OBJECTIVE: To demonstrate our experience with hysteroscopic assistance in the
      laparoscopic repair of an isthmocele. DESIGN: Surgical video article (Canadian
      Task Force classification III). SETTING: University hospital. INTERVENTION: A 42
      year-old woman with a history of previous caesarean section presented as an
      emergency with a large, seriously infected isthmocele. Once the infection was
      cured with antibiotics, sonography revealed a 23 * 14-mm isthmocele with 1.4-mm
      residual myometrium thickness. She reported postmenstrual spotting and
      dysmenorrhea of several years duration, as well as previous dyspareunia that had
      worsened after her cesarean section. Given her symptomatic isthmocele with thin
      residual myometrium and desire for childbearing, laparoscopic repair was offered.
      First, the bladder was dissected to expose the isthmus. Uterine arteries were
      dissected. Hysteroscopic guidance and transillumination revealed the edges of the
      defect. The isthmocele and fibrotic tissue were excised with cold scissors,
      minimizing cauterization. A hysterometer was placed in the uterine cavity to
      respect the cervical canal and posterior uterine wall, and the myometrium was
      then closed in 2 layers. The total surgical time was 120 minutes. The
      postoperative period was uneventful. At 2 months after surgery, sonography
      confirmed restoration, with a myometrium thickness of 8.3 mm. The patient was
      asymptomatic, except for dyspareunia. At 6 months after surgery, hysteroscopic
      examination was normal. We recommended that the patient avoid attempting
      pregnancy for 9 months. CONCLUSION: Hysteroscopic simultaneous assistance during
      laparoscopic isthmocele repair can be of great help in identifying the edges of
      the defect, especially in large cavities and in first cases, in which edges might
      not be clear otherwise. Resecting all of the fibrotic tissue while respecting
      healthy myometrium is essential. Excessive cauterization and ischemic suturing
      could prevent proper healing of the myometrium.

PMID- 29032252
TI  - Comparison of Industry-Leading Energy Devices for Use in Gynecologic Laparoscopy:
      Articulating ENSEAL versus LigaSure Energy Devices.
AB  - STUDY OBJECTIVE: To compare 2 laparoscopic bipolar electrosurgical devices used
      in total laparoscopic hysterectomy (TLH). An articulating advanced bipolar device
      (ENSEAL G2; Ethicon Endo-Surgery, Cincinnati, OH) and an electrothermal bipolar
      vessel sealer (LigaSure; Medtronic, Minneapolis, MN) were analyzed for
      differences in surgeon perception of ease of instrument use and workload using
      the NASA Raw Task Load Index (RTLX) scale. A second objective was to examine
      differences in operative time, estimated blood loss (EBL), and perioperative
      complication rates between the 2 devices. DESIGN: Single-institution, single
      blinded, randomized controlled trial (Canadian Task Force classification I).
      SETTING: Division of Minimally Invasive Gynecologic Surgery in a university
      hospital. PATIENTS: Eligibility required planned TLH, over age 18 years, and able
      to give informed consent; exclusions were stage III or IV endometriosis, known
      gynecologic malignancy, and early decision for conversion to laparotomy. One
      hundred seventy-eight patients screened, 142 enrolled, 2 withdrew, and 140
      completed the study. Patients were followed 1 month postoperatively.
      INTERVENTIONS: Preoperative randomization to articulating advanced bipolar device
      or electrothermal bipolar vessel sealer to be used during TLH. MEASUREMENTS AND
      MAIN RESULTS: At the end of each hysterectomy the primary surgeon completed an
      ergonomic assessment tool, the RTLX. Results were analyzed to detect differences
      in workload between the 2 devices. For each case the time to ligation of the
      bilateral uterine arteries, EBL, and complications (including device failure,
      blood transfusion, or other injury) were recorded. Statistical analysis was
      performed using the t test for normally distributed data, chi2 test for
      categorical data, and Mann-Whitney U-test for nonparametric data. There were no
      differences in age, body mass index, parity, prior surgery, uterine weight, race,
      indication, pathology, and comorbidities between the 2 groups. A statistically
      significant increase in RTLX scores (p < .0001), device failures (p = .0031), and
      time to ligation of bilateral uterine arteries (p = .0281) was noted in the
      articulating device group. No significant differences in EBL or complication
      rates were noted between the groups. CONCLUSIONS: The articulating advanced
      bipolar device was shown to have a statistically significant increase in surgeon
      perceived workload and rate of device failure when used in TLH; however, clinical
      and surgical outcomes were equivalent.

PMID- 29032253
TI  - Laparoscopic Dissection of Extensive Secondary Disseminated Peritoneal
      Leiomyomatosis.
AB  - STUDY OBJECTIVE: To demonstrate a minimal invasive surgical (MIS) technique for
      curative excision of extensive secondary disseminated peritoneal leiomyomatosis
      (DPL). DESIGN: The Institutional Review Board of Human Investigation and Ethics
      Committee of Chang Gung Medical Foundation ruled that approval was not required
      for this study. PATIENT: Woman aged 46 years. INTERVENTIONS, MEASUREMENTS, AND
      MAIN RESULTS: In MIS the myoma has to be divided into small fragments for
      piecemeal retrieval through a small incision [1] with a widely used technique
      called morcellation (confined or unconfined) [2]. DPL is a rare sequellae after
      laparoscopic morcellation. Because this entity is rarely reported, this video
      demonstrates laparoscopic technique for safe removal of DPL post laparoscopic
      myomectomy and morcellation. A 46-year-old woman with a past history of
      laparoscopic myomectomy with specimen retrieval by a power morcellation 8 years
      ago presented with abdominal discomfort. Computed tomography revealed multiple
      iso-dense lesions in the uterine corpus and pelvic cavity. Upon laparoscopy
      multiple nodules were identified at the previous myomectomy scar, pelvic
      peritoneum, ovarian surface, and over the small bowel. A total laparoscopic
      hysterectomy with bilateral salpingo-oophorectomy along with excision of all
      visible lesions was performed. CONCLUSIONS: In this video we demonstrate a safe
      retroperitoneal approach for complete excision of DPL. Laparoscopic hysterectomy
      or myomectomy with unconfined morcellation appears to be associated with the risk
      of DPL [3]. Complete tissue fragment retrieval will minimize the sequelae of
      morcellation. Hence, myoma remnants should be carefully extracted and confined
      morcellation should be considered. Because DPL causes significant distortion of
      pelvic anatomy, thorough knowledge of pelvic surgical anatomy and retroperitoneal
      approach for complete excision of all lesions is recommended.

PMID- 29032254
TI  - A Rare Case Report: Isolated Mediastinal Lymph Node Recurrence in High-Risk
      Endometrial Cancer at 5 Years after Primary Laparoscopic Surgery.
AB  - Endometrial cancer is the most common malignancy in some developed countries,
      with an estimated 102 423 new cases reported in 2015. Isolated mediastinal lymph
      node recurrence has not been reported previously in this setting. We report a 78
      year-old woman with an isolated lymph node recurrence in the mediastinal aortic
      region detected 5 years after her initial surgical treatment and postoperative
      adjuvant chemotherapy. Following curative radiotherapy with volumetric-modulated
      arc therapy at 60 Gy, the recurrence disappeared. To our knowledge, this is the
      first reported case of recurrent endometrial cancer with isolated mediastinal
      recurrence.

PMID- 29032255
TI  - Single-Incision Laparoscopic Surgery for Ovarian Tissue Cryopreservation.
AB  - STUDY OBJECTIVE: To present single-incision laparoscopic surgery (SILS) as an
      alternative to standard multiport laparoscopic surgery (MPLS) for ovarian tissue
      cryopreservation. DESIGN: Retrospective cohort study (Canadian Task Force
      classification II-2). SETTING: Tertiary medical center. PATIENTS: Two hundred
      thirty-one patients referred for oncologic fertility preservation. INTERVENTION:
      Non-inferiority comparison of SILS with MPLS for ovarian cryopreservation for
      future transplantation. MEASUREMENTS AND MAIN RESULTS: We compared duration of
      the procedure, intra- and postoperative complications, hospital stay, and time
      (days) from surgery to chemotherapy. We additionally compared number of ampules
      (each ampule contains 10 slivers of ovarian cortex tissue) preserved and number
      of oocytes retrieved during the preparation process. Adjustments for age,
      previous chemotherapy, and partial versus complete oophorectomy ratio were
      performed. MPLS was performed in 163 patients (71.2%) and SILS in 66 patients
      (28.8%). Ten patients (15.2%) in the SILS group and 32 (19.8%) in the MPLS group
      were prepubertal. Malignant conditions distribution was similar. Procedure
      duration and overall complication rates were similar. Number of ampules extracted
      from the preserved tissue was somewhat higher in the SILS group as compared with
      the MPLS group (14.7 vs 10.6, respectively; p < .01). CONCLUSION: Our findings
      suggest that SILS is an interesting alternative to MPLS. Future prospective
      trials may prove some benefit in ovarian tissue volume or time until chemotherapy
      initiation.

PMID- 29032256
TI  - Real-Time Fluorescent Sentinel Lymph Node Mapping with Indocyanine Green in Women
      with Previous Conization Undergoing Laparoscopic Surgery for Early Invasive
      Cervical Cancer: Comparison with Radiotracer +/- Blue Dye.
AB  - STUDY OBJECTIVE: To evaluate the added value of the fluorescence dye indocyanine
      green (ICG) for sentinel lymph node (SLN) mapping in women with cervical cancer
      who had undergone previous conization (stage 1A-1B1) by comparing ICG versus
      Tc99m radiotracer + blue dye (BD). DESIGN: Retrospective study (Canadian Task
      Force classification II-2). SETTING: Two European academic medical centers, San
      Gerardo Hospital, Italy and University of Berne, Switzerland. PATIENTS: Sixty
      five women with early stage (IA-IB1) cervical cancer who had undergone previous
      conization and who underwent SLN mapping with Tc99m +/- BD (n = 23) or ICG (n =
      42) followed by pelvic lymphadenectomy and fertility-sparing surgery or
      hysterectomy were included in this analysis. INTERVENTION: Overall detection rate
      and bilateral SLN mapping rates of ICG were compared with those obtained using
      the standard Tc99m radiocolloid and BD. MEASUREMENT AND MAIN RESULTS: Overall,
      220 SLNs were detected. The median number of SLNs per patient in the Tc99m +/- BD
      group was 2 (range, 1-5) and in the ICG group, 3 (range, 2-15). The detection
      rate of SLNs was 95.7% in Tc99m +/- BD group and 100% in the ICG group (p =
      .354). The women injected with ICG had a higher rate of bilateral mapping of the
      SLNs as compared with the Tc99m +/- BD group (95.2% vs 69.6%, p = .016%). Only
      12% of the patients (8/65) presented metastatic nodes, 2 in the Tc99m +/- BD
      group and 6 in the ICG group. CONCLUSION: In early-stage cervical cancer patients
      conization had no significant impact on the SLN detection rate using both
      techniques (ICG and radiotracer +/- BD). In this scenario a higher bilateral
      mapping rate was confirmed using the fluorescent dye ICG rather than the standard
      techniques.

PMID- 29032257
TI  - Hetero-catalytic hydrothermal oxidation of simulated pulping effluent: Effect of
      operating parameters and catalyst stability.
AB  - In the present study, activated carbon (AC) supported bi-metallic catalyst
      (3.3Cu/2.2Ce/4.4AC) was subjected to catalytic wet oxidation (CWO) of simulated
      pulping effluent at moderate operating conditions (temperatures = 120-190 
      degrees C and oxygen partial pressures = 0.5-1.2 MPa). The oxidation reaction was
      performed in a high pressure reactor (capacity = 0.7 l) with catalyst
      concentration of 1-5 g/l for 3 h duration. During CWO at 190  degrees C
      temperature and 0.9 MPa oxygen pressure, the chemical oxygen demand (COD), total
      organic carbon (TOC), lignin and color removals from the wastewater were 79%,
      77%, 88% and 89%, respectively, while the wastewater biodegradability was
      enhanced to 0.52 from an initial value of 0.16. TOC mass balance suggested that
      nearly 86-97% of the degraded TOC was mineralized whereas copper and cerium
      leaching from the catalyst were in the range of 1-15% and 0.7-1% with respect to
      their initial amounts. Metal leaching was reduced with increase in the reaction
      temperature. Global kinetic rate model was also developed using TOC degradation
      data and the activation energies of two step (rapid followed by slower TOC
      removal) CWO reaction were determined as 34.2 kJ/mol and 28.5 kJ/mol,
      respectively.

PMID- 29032258
TI  - Modelling approach to better control biofouling in fluidized bed membrane
      bioreactor for wastewater treatment.
AB  - A mathematical model has been developed to better understand fouling mitigation
      mechanisms in particle-sparged membrane bioreactor. The model developed herein
      assumes two fouling mechanisms, (i) the pore blocking leading to the decrease in
      membrane surface porosity and (ii) the progressive development of compressible
      cake layer on the membrane surface. The model has been validated by comparison
      with trans-membrane pressure data registered from the bioreactor filtering a
      synthetic solution consisting of bentonite, sodium alginate and bovin serum
      albumine (BSA). Two nonporous media have been tested, Polyethylene terephthalate
      (PET) beads and silica particles with different dosage (0, 10, 30, 50 and 70%
      (v/v)). Compared to the experimental data, the model shows satisfactory fitting
      with R2 >= 93%. For both media tested, an optimal dosage to minimize fouling rate
      was observed at 50% (v/v). Even if both fouling mechanisms have been mitigated by
      adding fluidized media, pore blocking was more pronounced than cake formation.
      Moreover, better pore blocking mitigation was observed with PET media (50% (v/v))
      having bigger size and lower density than silica particles.

PMID- 29032259
TI  - Effect of evaporative weathering and oil-sediment interaction on the fate and
      behavior of diluted bitumen in marine environments. Part 2. The water
      accommodated and particle-laden hydrocarbon species and toxicity of the aqueous
      phase.
AB  - In this study, the water accommodated and particle-laden hydrocarbon species, and
      the toxicity of the aqueous phase after oil-sediment interactions by varying the
      weathering states of diluted bitumen (Cold Lake blend (CLB)), oil type from light
      to heavy, and sediment type. Compared to the original oils, the sediment-laden
      total petroleum hydrocarbons (TPH) contained fewer hydrocarbons in the carbon
      range <C10, comparable contents in C10-C16 range, higher contents in both the C16
      C34 and >C34 range. Sediment-laden oil amounts generally decreased with an
      increased viscosity and asphaltene content of the test oils, as well as with
      increased sediment particle size. The presence of sediments significantly
      decreased the oil accommodated in water due to the formation of oil particulate
      aggregates (OPA) after mixing and settling. Less water accommodated TPH and
      polycyclic aromatic hydrocarbons (PAHs) were observed for weathered CLB products.
      However, oil and sediment types did not clearly affect the water accommodated TPH
      and PAHs. Light molecular PAHs and their alkylated congeners accounted for most
      of the water accommodated PAH congeners. A microtoxicity test demonstrated that
      with or without sediment, and regardless of sediment type, the toxicity of the
      water phase did not change significantly. Light oil of Alberta sweet mixed blend
      (ASMB) had the highest toxicity, followed by fresh CLB, and then all other oils,
      suggesting that ASMB and fresh CLB had relatively higher levels of light toxic
      components dissolved in the water phase compared with the other tested oils.

PMID- 29032260
TI  - Photo-assisted degradation of 2, 4, 6-trichlorophenol by an advanced reduction
      process based on sulfite anion radical: Degradation, dechlorination and
      mineralization.
AB  - This research was aimed at evaluating the performance UV only and sulfite
      mediated photoreduction process (an advanced reduction process) in the
      degradation, dechlorination and mineralization of 2, 4, 6-trichlorophenol (TCP).
      Firstly efficiency of sulfite-mediated photoreduction (SMP) process in the
      degradation of TCP was investigated and obtained the complete degradation of TCP
      (250 mg L-1) under the selected conditions (pH, 7.0; [sulfite]/[TCP] = 3.13; UV
      irradiation, 87 MUW cm-2 and dissolved oxygen (DO), 2 mg L-1) at 80 min whereas
      degradation rate of TCP by UV only was 73% at similar time. Investigate of
      degradation mechanism revealed the higher ability of sulfite radicals (SO3-) than
      eaq- and H in the reduction of TCP by the SMP process. In the second stage, UV
      only and SMP process efficiencies were investigated in the dechlorination of TCP.
      The dechlorination percentage (cleavage of CCl bonds) of TCP (250 mg L-1) for UV
      only and SMP process was 36 and 98% respectively. The contrary of TCP degradation
      process, investigation of reaction mechanism for TCP dechlorination process
      elucidated eaq- along with SO3- have important role in the dechlorination of TCP
      (although, the SO3- role was significant than the eaq-). In the next stage,
      mineralization of TCP using SMP process was evaluated by chemical oxygen demand
      (COD) and related result was 30.2%. The aromatic intermediates such as 2-chloro-1
      benzoquinone, 2-hydroxy benzoquinone, 2-chlorophenol, benzene, 1, 3
      cyclohexadiene and cyclohexene are identified by using LC-ESI/MS analysis.

PMID- 29032261
TI  - Electrochemically enhanced microbial CO conversion to volatile fatty acids using
      neutral red as an electron mediator.
AB  - Conversion of C1 gas feedstock, including carbon monoxide (CO), into useful
      platform chemicals has attracted considerable interest in industrial
      biotechnology. Nevertheless, the low conversion yield and/or growth rate of CO
      utilizing microbes make it difficult to develop a C1 gas biorefinery process. The
      Wood-Ljungdahl pathway which utilize CO is a pathway suffered from insufficient
      electron supply, in which the conversion can be increased further when an
      additional electron source like carbohydrate or hydrogen is provided. In this
      study, electrode-based electron transference using a bioelectrochemical system
      (BES) was examined to compensate for the insufficient reducing equivalent and
      increase the production of volatile fatty acids. The BES including neutral red
      (BES-NR), which facilitated electron transfer between bacteria and electrode, was
      compared with BES without neutral red and open circuit control. The coulombic
      efficiency based on the current input to the system and the electrons recovered
      into VFAs, was significantly higher in BES-NR than the control. These results
      suggest that the carbon electrode provides a platform to regulate the redox
      balance for improving the bioconversion of CO, and amending the conventional C1
      gas fermentation.

PMID- 29032262
TI  - Effect of cadmium accumulation on green algae Chlamydomonas reinhardtii and acid
      tolerant Chlamydomonas CPCC 121.
AB  - Cadmium is one of the most dangerous metals found in wastewater since exposure to
      low concentrations are highly toxic for cellular functions. In this study, the
      effect of cadmium accumulation on Chlamydomonas reinhardtii and acid-tolerant
      strain CPCC 121 was investigated during 48 h under 100-600 MUM of Cd and two pH
      conditions (4 and 7). The toxicity of accumulated Cd was determined by the change
      of cellular and photosynthetic parameters. Obtained results showed that the
      maximum capacity of Cd accumulation in algal biomass was reached for both strains
      at 24 h of exposure to 600 MUM of Cd. Under this condition, C. reinhardtii showed
      a higher uptake of Cd compared to the strain CPCC 121, inducing a stronger
      cellular toxic impact. Chlamydomonas CPCC 121 showed a tolerance for Cd due to
      the exclusion of Cd at the cell wall surface, which was higher at pH 4 than pH 7.
      TEM images and EDX spectrum of Cd distribution within the cell confirmed the role
      of the cell wall as a barrier for Cd uptake. Although Cd2+ concentration was the
      highest in the medium, CPCC 121 was the most tolerant at pH 4, but was not enough
      efficient to be considered for the phycoremediation of Cd. At neutral pH, the
      efficiency of C. reinhardtii for the removal of Cd was limited by its toxicity,
      which was dependent to the concentration of Cd in the medium and the time of
      exposure.

PMID- 29032263
TI  - Comparison of DGT with traditional extraction methods for assessing arsenic
      bioavailability to Brassica chinensis in different soils.
AB  - Several predictive models and methods have been used for heavy metals
      bioavailability, but there is no universally accepted approach in evaluating the
      bioavailability of arsenic (As) in soil. The technique of diffusive gradients in
      thin-films (DGT) is a promising tool, but there is a considerable debate with
      respect to its suitability. The DGT method was compared with other traditional
      chemical extractions techniques (soil solution, NaHCO3, NH4Cl, HCl, and total As
      method) for estimating As bioavailability in soil based on a greenhouse
      experiment using Brassica chinensis grown in various soils from 15 provinces in
      China. In addition, we assessed whether these methods are independent of soil
      properties. The correlations between plant and soil As concentration measured
      with traditional extraction techniques were pH and iron oxide (Feox) dependent,
      indicating that these methods are influenced by soil properties. In contrast, DGT
      measurements were independent of soil properties and also showed a better
      correlation coefficient than other traditional techniques. Thus, DGT technique is
      superior to traditional techniques and should be preferable for evaluating As
      bioavailability in different type of soils.

PMID- 29032264
TI  - Building a Safer and Faster CAR: Seatbelts, Airbags, and CRISPR.
AB  - Therapeutic T cell engineering has recently garnered widespread interest because
      of the success of CD19 chimeric antigen receptor (CAR) therapy. CARs are
      synthetic receptors for antigen that redirect the specificity and reprogram the
      function of the T cells in which they are genetically introduced. CARs targeting
      CD19, a cell surface molecule found in most leukemias and lymphomas, have yielded
      high remission rates in patients with chemorefractory, relapsed disease,
      including acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non
      Hodgkin lymphoma. The toxicities of this treatment include B cell aplasia,
      cytokine release syndrome (CRS), and neurotoxicity. Although reversible in most
      instances, these toxicities may require specific medical interventions, including
      transfer to intensive care to treat severe CRS. Guidelines for managing these
      toxicities are emerging. The recent report of a nonhuman primate model for CRS is
      poised to help advance the management of this syndrome. Finally, new engineering
      modalities, based on the use of targeted nucleases like CRISPR, may further
      enhance the efficacy and safety of CAR T cells.

PMID- 29032265
TI  - Effect of Antithymocyte Globulin Source on Outcomes of HLA-Matched Sibling
      Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Severe
      Aplastic Anemia.
AB  - We wanted to evaluate efficacy of porcine antithymocyte globulin (ATG) in HLA
      matched sibling donor allogeneic hematopoietic stem cell transplantation (MSD
      HSCT) for patients with severe aplastic anemia (SAA). The clinical data of 113
      SAA patients who received MSD-HSCT from January 2005 to November 2016 were
      analyzed retrospectively. Of these, 58 patients received rabbit ATG as a part of
      conditioning regimen (R-ATG group), whereas the other 55 patients received
      porcine ATG (P-ATG group). Patient baseline characteristics and donor conditions
      of the 2 groups were similar, except patients were older and more received
      peripheral blood stem cell transplantation in the P-ATG group. All patients
      engrafted in 2 groups. There were significant differences in the incidence of
      acute (20.7% +/- 5.3% versus 43.4% +/- 7.0%, P = .015) and chronic graft-versus-
      host disease (GVHD; 20.1% +/- 5.8% versus 46.0% +/- 7.9%, P = .003) between the R
      ATG and P-ATG groups. However, there were no significant differences in terms of
      3-year overall survival (93.1% +/- 3.3% versus 84.4% +/- 5.7%, P = .235), grades
      III to IV acute GVHD (3.4% +/- 2.4% versus 12.3% +/- 4.7%, P = .098), moderate to
      severe chronic GVHD (12.6% +/- 4.9% versus 11.5% +/- 4.9%, P = .905), or graft
      rejection (7.4% +/- 3.6% versus 5.5% +/- 3.1%, P = .852). There was also no
      significant difference with regard to the incidence of severe bacterial infection
      (P = .075), invasive fungal disease (P = .701), or cytomeglovirus viremia (P =
      .770). P-ATG showed satisfactory efficacy and safety compared with R-ATG in the
      setting of MSD-HSCT for SAA patients. P-ATG could be a potential alternative
      preparation for R-ATG, further offering the advantage of lower costs.

PMID- 29032266
TI  - Hypoalbuminemia at Day +90 Is Associated with Inferior Nonrelapse Mortality and
      Overall Survival in Allogeneic Hematopoietic Cell Transplantation Recipients: A
      Confirmatory Study.
AB  - Prognostic biomarkers in allogeneic hematopoietic cell transplantation (allo-HCT)
      are needed to improve risk assessment and help guide therapeutic and surveillance
      strategies to mitigate the risk of death from the procedure. We previously
      identified hypoalbuminemia at day +90 post-transplantation as an independent
      predictor of increased nonrelapse mortality (NRM) and inferior overall survival
      (OS) in patients with acute myelogenous leukemia and myelodysplastic syndrome who
      were treated with an allo-HCT. Here, we aim to confirm the prognostic
      significance of day +90 hypoalbuminemia in 783 patients, median age 52 years
      (range, 18 to 76), who received an allo-HCT for various hematologic malignancies
      and bone marrow failure syndromes. Multivariate analysis for NRM demonstrated a
      negative effect of low serum albumin levels (<3.0 versus 3.0 to 3.5 versus >3.5
      g/dL) at day +90 post-transplantation (hazard ratios, 8.03 [95% CI, 3.59 to
      17.97] versus 2.84 [95% CI, 1.59 to 5.08] versus reference; P < .0001). This was
      also the case for OS (hazard ratios, 6.86 [95% CI, 4.24 to 11.10] versus 1.52
      [95% CI, 1.05 to 2.20] versus reference; P < .0001). Patients with
      hypoalbuminemia at day +90 post-transplantation are more likely to die from
      causes other than relapse, particularly infections. This large study confirms the
      ability of day +90 serum hypoalbuminemia to predict worse NRM and inferior OS.
      Presence of hypoalbuminemia at day +90 should drive a more rigorous real-time
      surveillance strategy considering the anticipated high-risk of NRM and poor
      survival in these patients. Future studies should consider incorporating day +90
      serum albumin levels in prognostic models of NRM and OS.

PMID- 29032267
TI  - Long-Term Follow-Up of a Donor versus No-Donor Comparison in Patients with
      Multiple Myeloma in First Relapse after Failing Autologous Transplantation.
AB  - We report the long-term clinical outcomes of a retrospective multicenter study
      that enrolled 169 patients with multiple myeloma (MM) in first relapse after
      failing autologous stem cell transplantation (SCT). After HLA typing at relapse,
      79 patients with a suitable donor, 72 (91%) of whom eventually underwent salvage
      allogeneic SCT (allo-SCT), were compared with 90 patients without a donor who
      were treated with multiple lines of salvage treatment with bortezomib and/or
      immunomodulatory agents. At a median follow-up of 30 months (range, 2-180 months)
      for all patients and 110 months (range, 38-180 months) for surviving patients, 7
      year progression-free survival (PFS) was 18% in the donor group and 0% in the no
      donor group (hazard ratio [HR], 2.495; 95% confidence interval [CI], 1.770-3.517;
      P < .0001). Seven-year overall survival (OS) was 31% in the donor group and 9% in
      the no-donor group (HR, 1.835; 95% CI, 1.306-2.577; P < .0001). By multivariate
      analysis, chemosensitivity to salvage treatments and presence of a suitable donor
      were significantly associated with better PFS and OS. The long-term follow-up of
      this study confirms the significant PFS benefit and provides new evidence of an
      OS advantage for patients with MM who have a suitable donor and undergo allo-SCT.
      Allo-SCT should be considered as a treatment option in young relapsed patients
      with high-risk disease features after first-line treatment.

PMID- 29032268
TI  - Total Marrow Lymphoid Irradiation/Fludarabine/ Melphalan Conditioning for
      Allogeneic Hematopoietic Cell Transplantation.
AB  - Reduced-intensity conditioning (RIC) regimens for hematopoietic stem cell
      transplantation (HCT) can reduce morbidity and mortality, but patients with
      advanced disease may require alternative approaches. In an initial report of RIC
      with fludarabine (FLU) and melphalan (MEL) with total marrow lymphoid irradiation
      (TMLI) in HCT for advanced hematologic malignancies in 33 patients, we found that
      the addition of TMLI to RIC was feasible and safe. Here we report long-term
      outcomes for these patients. This prospective study included 61 patients treated
      with TMLI to a dose of 12 Gy (1.5 Gy twice daily for 4 days), FLU (25 mg/m2/day
      for 5 days), and MEL (140 mg/m2/day for 1 day). Overall survival (OS), event-free
      survival (EFS), cumulative incidence of relapse (CIR), and nonrelapse mortality
      (NRM) were measured from the date of HCT. Survival outcomes were analyzed using
      Kaplan-Meier analysis. Patients were categorized as low/intermediate or high/very
      high risk using the Disease Risk Index. The median follow-up was 7.4 years. The
      majority of patients had acute leukemia (72%); 49% had high/very high-risk
      disease. The median patient age was 55 years (range, 9-70 years). Two-year OS,
      EFS, CIR, and NRM were 54% (95% confidence interval [CI], 41%-66%), 49% (95% CI,
      36%-61%), 21% (95% CI, 13%-35%), and 30% (95% CI, 20%-43%), respectively. Five
      year OS, EFS, CIR, and NRM were 42% (95% CI, 30%-54%), 41% (95% CI, 28%-53%), 26
      (95% CI, 17%-40%), and 33% (95% CI, 23%-47%, respectively). Acute (any grade) and
      chronic (limited or extensive) graft-versus-host disease occurred in 69% and 74%
      of patients, respectively. The most common toxicity was mucositis. The addition
      of TMLI to FLU/MEL conditioning was well tolerated, with favorable outcomes.
      Dosage escalation of TMLI or other modifications may be needed to improve disease
      control.

PMID- 29032269
TI  - Second Hematopoietic Stem Cell Transplant for Thalassemia Major: Improved
      Clinical Outcomes with a Treosulfan-Based Conditioning Regimen.
AB  - Graft rejection (GR) after allogeneic stem cell transplantation (allo-SCT) occurs
      in 10% to 20% of patients with beta-thalassemia major (TM). There are limited
      data on the clinical profile and long-term outcome of patients who have had a GR.
      We undertook a retrospective analysis of patients who had a graft failure after
      allo-SCT for TM at our center. From October 1991 to June 2016, 55 of 506 patients
      (11%) transplanted for TM had a graft failure. An additional 7 patients with
      graft failure after allo-SCT done at other centers were referred to us for a
      second transplant. The median age was 8 years (range, 1 to 19), and there were 38
      males (61.2%). Thirty-two patients (52.4%) were primary graft failures (15 with
      aplasia and 17 with autologous recovery) and 30 (47.6%) were secondary graft
      failures (5 with aplasia and 25 with autologous recovery). On conventional risk
      stratification 40 patients (64.5%) were class III. Seventeen patients (53.12%)
      with primary graft failure and 16 (53.3%) with secondary graft failure did not
      receive a second transplant. Twenty-nine patients (46%) with GR underwent a
      second allo-SCT. With the exception of 1 patient (first allo-SCT with an
      unrelated cord blood product), the donor for the second transplant was the same
      as the first transplant. Conditioning regimen for the second SCT was busulfan
      based myeloablative (MAC) in 7 patients (24%), treosulfan-based MAC in 12
      patients (41.3%), and the remaining received non-MAC regimens in view of
      pancytopenia and perceived inability to tolerate MAC. None of the patients
      conditioned with a treosulfan-based regimen had a GR, although 1 patient died
      with complications secondary to chronic graft-versus-host disease. Of the
      remaining 17 patients, 10 died after the second GR and 3 of regimen-related
      toxicity. Four are alive, of which 1 has recurrent TM and the rest are well and
      transfusion independent at 55, 80, and 204 months, respectively, from second
      transplant (all busulfan-based MAC). On a univariate analysis a nontreosulfan
      based conditioning regimen and time from GR to second transplant of <1 year was
      significantly associated with an adverse impact. However, on a multivariate
      analysis only a nontreosulfan-based regimen was associated with a significant
      adverse impact on event-free survival (HR, 11.5; 95% CI, 1.13 to 116.4; P =
      .039). In conclusion, there has been a significant improvement in clinical
      outcomes in our experience with the use of a treosulfan-based reduced-toxicity
      MAC regimen for second allo-SCT for TM. It would be reasonable, where feasible,
      to defer the second transplant by a year after the first GR.

PMID- 29032270
TI  - A European HLA Isolate and Its Implications for Hematopoietic Stem Cell
      Transplant Donor Procurement.
AB  - Europeans have often been considered a homogenous group in registry donor match
      predictions, but it is now evident that HLA haplotype frequencies vary across the
      European continent. Earlier studies have indicated that Finns in northeastern
      Europe have unique HLA characteristics, and the increasing availability of high
      resolution registry donor data is now making more detailed comparisons possible.
      In the first phase of the present study, estimated HLA haplotype frequencies in
      stem cell donor registries of Finland and its neighbors Sweden and Russia were
      calculated using the algorithm of the German National Bone Marrow Donor Registry
      (ZKRD) and their frequencies were compared with one another and also with that of
      Germany. Virtual donor searches for 1492 high-resolution typed Finnish patients
      in the Finnish, Swedish and German registries were then performed, using
      individual match predictions for each registry. In the last phase, the impact of
      specifically Finnish-enriched HLA haplotypes on Finnish patients and the use of
      Finnish registry donors was assessed by analyzing 647 consecutive hematopoietic
      stem cell transplantation (HSCT) donor searches and 40 exported Finnish HSCTs.
      The Finnish HLA landscape was more homogenous than the 3 other studied
      populations, but also genetically distinct from them. The match predictions found
      a probable 10/10 match for 71%, 41%, and 31% of the Finnish patients in the
      German, Finnish, and Swedish registries, respectively. Thirty-four of Finland's
      100 most frequent HLA haplotypes were represented with a frequency of <.0003 in
      Germany, and with an 8- to 3262-fold greater frequency in Finland than in
      Germany. Patients carrying these Finnish-enriched haplotypes were less likely to
      receive a matched HSCT but more likely to receive it from a domestic donor.
      Registry donors carrying them were more likely to donate stem cells, both
      nationally and internationally. The Finnish HLA isolate has a significant impact
      on both Finnish patients and registry donors, explaining the high use of national
      registry donors for Finnish patients. Haplotype frequency estimations are an
      important tool for small registries as well, to help optimize donor match
      predictions and the size of individual registries.

PMID- 29032271
TI  - A Comparative Assessment of Quality of Life in Patients with Multiple Myeloma
      Undergoing Autologous Stem Cell Transplantation Through an Outpatient and
      Inpatient Model.
AB  - Outpatient autologous stem cell transplantation (ASCT) has proven to be feasible
      in terms of physical morbidity and mortality outcomes, but little data exist on
      the impact of this procedure on quality of life (QoL). The purpose of this
      prospective, observational, longitudinal cohort study was to compare the effects
      of inpatient (n = 76) and outpatient (n = 64) modes of care on QoL in patients
      with multiple myeloma who underwent ASCT. Patients were treated according to
      their preference for the inpatient or outpatient model. QoL was assessed using
      the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT
      BMT) at baseline (7 days before ASCT; T1) and at days +7 (T2) and +30 (T3) after
      ASCT. Overall, inpatients achieved higher mean values at each time point (86.05
      +/- 15.54 at T1, 89.23 +/- 19.19 at T2, and 87.96 +/- 13.6 at T3) compared with
      outpatients (85.62 +/- 14.51 at T1, 87.42 +/- 23.41 at T2, and 83.98 +/- 20.2 at
      T3), although the differences did not reach statistical significance. Inpatients
      showed higher mean scores than outpatients in physical well-being (7.67 +/- 5.7,
      15.44 +/- 6.34, and 12.96 +/- 6.03, respectively, versus 5.89 +/- 4.33, 13.92 +/-
      7.05, and 8.84 +/- 6.33, respectively; P < .05). Mean scores on social/family
      well-being were significantly higher in the outpatient group compared with the
      inpatient group (22.93 +/- 13.29, 21.14 +/- 5.31, and 21.64 +/- 4.58,
      respectively, versus 20.59 +/- 3.79, 19.52 +/- 5.12, and 20.01 +/- 3.97,
      respectively; P = .003). There were no significant between-group differences with
      respect to functional well-being and emotional status. Among adults at a single
      institution undergoing ASCT for MM, the use of outpatient care compared with
      standard transplantation care did not result in improved QoL during
      transplantation. Further research is needed for replication and to assess longer
      term outcomes and implications.

PMID- 29032273
TI  - Torquetenovirus Dynamics and Immune Marker Properties in Patients Following
      Allogeneic Hematopoietic Stem Cell Transplantation: A Prospective Longitudinal
      Study.
AB  - Torquetenovirus (TTV) has been proposed as a marker of immune function in
      patients receiving immunosuppression after solid organ transplantation. This
      study aimed to define TTV plasma dynamics and investigate clinical associations
      in patients following allogeneic hematopoietic stem cell transplantation (HSCT).
      This was a single-center prospective longitudinal study involving 50 consecutive
      patients treated with HSCT between March 2015 and April 2016. TTV plasma DNA
      levels were measured with quantitative PCR at 12 consecutive time points during
      the first year after HSCT. Forty of the 50 patients (80%) had detectable TTV
      viremia before HSCT (median level, 5.37 log10 copies/mL; interquartile range
      [IQR], 3.51-6.44 log10 copies/mL). All patients subsequently developed TTV
      viremia during the follow-up period. Plasma viral loads evolved dynamically over
      time, with a peak of 8.32 log10 copies/mL (IQR, 7.33-9.35 log10 copies/mL)
      occurring at 79 days (IQR, 50-117 days) following HSCT and a stable plateau
      toward the end of the follow-up period. The type of malignancy, the use of
      antithymocyte globulin during conditioning, and the occurrence of acute graft
      versus-host disease requiring systemic therapy had temporary effects on TTV
      dynamics. TTV levels showed a significant correlation with absolute lymphocyte
      counts following engraftment (rs = -.27; P < .01) and with cytomegalovirus (CMV;
      rs=.39; P < .01) and Epstein-Barr virus (EBV; rs=.45; P = .02) viral loads during
      phases of viremia. Immune-related clinical events were not predicted by TTV
      levels. TTV viremia occurred universally and was sustained throughout the first
      year after HSCT. Several variables and events before and after HSCT were
      correlated with TTV levels and hint toward immune marker properties of TTV, but
      their complex interactions might perturb the capability of TTV to predict immune
      related complications in this population.

PMID- 29032272
TI  - Fludarabine and Busulfan versus Fludarabine, Cyclophosphamide, and Rituximab as
      Reduced-Intensity Conditioning for Allogeneic Transplantation in Follicular
      Lymphoma.
AB  - Large, multicenter studies comparing commonly used reduced-intensity conditioning
      (RIC) approaches in follicular lymphoma (FL) have not been performed. Using the
      Center for International Blood and Marrow Transplant Research database, we report
      the outcomes of the 2 most commonly used RIC approaches, fludarabine and busulfan
      (Flu/Bu) versus fludarabine, cyclophosphamide, and rituximab (FCR) in FL
      patients. We evaluated 200 FL patients undergoing allogeneic hematopoietic cell
      transplantation (allo-HCT) who received RIC with either Flu/Bu (n = 98) or FCR (n
      = 102) during 2008 to 2014. All patients received peripheral blood grafts, and
      graft-versus-host disease (GVHD) prophylaxis was limited to calcineurin inhibitor
      based approaches. Median follow-up of survivors in the Flu/Bu and FCR groups was
      48 months and 46 months, respectively. On univariate analysis in the Flu/Bu and
      FCR groups, the 3-year rates of nonrelapse mortality (11% versus 11%, P = .94),
      relapse/progression (18% versus 15%, P = .54), progression-free survival (PFS)
      (71% versus 74%, P = .65), and overall survival (OS) (73% versus 81%, P = .18)
      were not significantly different. On multivariate analysis no difference was seen
      between the FCR and Flu/Bu cohorts in terms of grades II to IV (relative risk
      [RR], 1.06; 95% confidence interval [CI], .59 to 1.93; P = .84) or grades III to
      IV (RR, 1.18; 95% CI, .47 to 2.99; P = .72) acute GVHD, nonrelapse mortality (RR,
      .83; 95% CI, .38 to 1.82; P = .64), relapse/progression (RR, .99; 95% CI, .49 to
      1.98; P = .97), PFS (RR, .92; 95% CI, .55 to 1.54; P = .76), or OS (RR, .70; 95%
      CI, .40 to 1.23; P = .21) risk. However, RIC with FCR was associated with a
      significantly reduced chronic GVHD risk (RR, .52; 95% CI, .36 to .77; P = .001).
      RIC with either Flu/Bu or FCR in patients with FL undergoing allo-HCT provides
      excellent 3-year OS, with acceptable rates of nonrelapse mortality. FCR-based
      conditioning was associated with a lower risk of chronic GVHD.

PMID- 29032274
TI  - Assessment of Impact of HLA Type on Outcomes of Allogeneic Hematopoietic Stem
      Cell Transplantation for Chronic Lymphocytic Leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many
      highly effective therapies. Chemorefractory disease, often characterized by
      deletion of chromosome 17p, has historically been associated with very poor
      outcomes, leading to the application of allogeneic hematopoietic stem cell
      transplantation (allo-HCT) for medically fit patients. Although the use of allo
      HCT has declined since the introduction of novel targeted therapy for the
      treatment of CLL, there remains significant interest in understanding factors
      that may influence the efficacy of allo-HCT, the only known curative treatment
      for CLL. The potential benefit of transplantation is most likely due to the
      presence of alloreactive donor T cells that mediate the graft-versus-leukemia
      (GVL) effect. The recognition of potentially tumor-specific antigens in the
      context of class I and II major histocompatibility complex on malignant B
      lymphocytes by donor T cells may be influenced by subtle differences in the
      highly polymorphic HLA locus. Given previous reports of specific HLA alleles
      impacting the incidence of CLL and the clinical outcomes of allo-HCT for CLL, we
      sought to study the overall survival and progression-free survival of a large
      cohort of patients with CLL who underwent allo-HCT from fully HLA-matched related
      and unrelated donors at Center for International Blood and Marrow Transplant
      Research transplantation centers. We found no statistically significant
      association of allo-HCT outcomes in CLL based on previously reported HLA
      combinations. Additional study is needed to further define the immunologic
      features that portend a more favorable GVL effect after allo-HCT for CLL.

PMID- 29032275
TI  - Association of Socioeconomic Status with Chronic Graft-versus-Host Disease
      Outcomes.
AB  - Chronic graft-versus host disease (GVHD) is a chronic and disabling complication
      after hematopoietic cell transplantation (HCT). It is important to understand the
      association of socioeconomic status (SES) with health outcomes in patients with
      chronic GVHD because of the impaired physical health and dependence on intensive
      and prolonged health care utilization needs in these patients. We evaluated the
      association of SES with survival and quality of life (QOL) in a cohort of 421
      patients with chronic GVHD enrolled on the Chronic GVHD Consortium Improving
      Outcomes Assessment study. Income, education, marital status, and work status
      were analyzed to determine the associations with patient-reported outcomes at the
      time of enrollment, nonrelapse mortality (NRM), and overall mortality. Higher
      income (P = .004), ability to work (P < .001), and having a partner (P = .021)
      were associated with better mean Lee chronic GVHD symptom scores. Higher income
      (P = .048), educational level (P = .044), and ability to work (P < .001) also
      were significantly associated with better QOL and improved activity. In
      multivariable models, higher income and ability to return to work were both
      significantly associated with better chronic GVHD Lee symptom scores, but income
      was not associated with activity level, QOL, or physical/mental functioning. The
      inability to return to work (hazard ratio, 1.82; P = .019) was associated with
      worse overall mortality, whereas none of the SES indicators were associated with
      NRM. Income, race, and education did not have statistically significant
      associations with survival. In summary, we did not observe an association between
      SES variables and survival or NRM in patients with chronic GVHD, although we
      found some association with patient-reported outcomes, such as symptom burden.
      Higher income status was associated with less severe chronic GVHD symptoms. More
      research is needed to understand the psychosocial, biological, and environmental
      factors that mediate this association of SES with major HCT outcomes.

PMID- 29032276
TI  - Reversal of Low Donor Chimerism after Hematopoietic Cell Transplantation Using
      Pentostatin and Donor Lymphocyte Infusion: A Prospective Phase II Multicenter
      Trial.
AB  - In a multicenter, prospective, phase II study we evaluated the safety and
      efficacy of pentostatin followed by donor lymphocyte infusion (DLI) in patients
      with low donor Tcell chimerism after allogeneic hematopoietic cell
      transplantation (HCT). Thirty-six patients with low donor blood CD3 chimerism
      were enrolled in this study. Thirty-five patients received a total of 41 DLIs
      after a dose of pentostatin, and 1 patient received pentostatin only. Median
      donor CD3 chimerism prompting the initiation of pentostatin and DLI was 28%
      (range, 5% to 47%). Responses (defined by increases in donor CD3 chimerism >=10%
      maintained to day 56 post-DLI) were seen in 16 patients (44.4%) with a median
      rise in CD3 donor chimerism to 64% (range, 48% to 100%). There was a trend for
      better responses among 21 patients who received first treatment within 100 days
      after transplant (57% response rate) compared with15 patients who received first
      treatment more than 100 days after HCT (27% response rate, P = .07). Fourteen
      patients (39%) developed grades II to IV acute graft-versus-host disease (GVHD)
      at a median of 10 days (range, 0 to 83) after DLI. Ten patients (28%) developed
      extensive chronic GVHD. Seventeen patients (47%) developed new grade 4 cytopenias
      after DLI. There was no difference in relapse between nonresponders and
      responders. Twenty-eight patients (78%) died, most (n = 21) because of relapse.
      Five of 16 responders (31%) are alive, all disease-free, at a median of 60 months
      (range, 21 to 132) after DLI. Six of 20 nonresponders (30%) are alive at a median
      of 47 months (range, 16 to 100) after DLI, 3 in complete remission. Pentostatin
      and DLI had acceptable toxicity and appeared to increase low donor CD3 chimerism
      after HCT but had no impact on mortality.

PMID- 29032277
TI  - Marine ecological risk assessment methods for radiation accidents.
AB  - Ecological risk assessment (ERA) is a powerful technical tool that can be used to
      analyze potential and extreme adverse environmental impacts. With the rapid
      development of nuclear power plants in coastal areas around the world, the
      establishment of approaches and methodologies for marine ERA with a focus on
      radiation accidents is an urgent requirement for marine environmental management.
      In this study, the approaches and methodologies for ERA pertaining to marine
      radiation accidents (MRA) are discussed and summarized with applications in case
      studies, such as the nuclear accident in Fukushima, Japan, and a hypothetical
      accident in Daya Bay, China. The concepts of ERA and Risk Degree of ERA on MRA
      are defined for the first time to optimize the ERA system. The results of case
      studies show that the ERA approach and methodology for MRA are scientifically
      sound and effective in both the early and late stage of MRAs along with classic
      ERA Approach and the ERICA Integrated Approach. The results can be useful in the
      decision-making processes and the risk management at the beginning of accident as
      well as the ecological restoration after the accident.

PMID- 29032278
TI  - Rapid detection of frozen-then-thawed minced beef using multispectral imaging and
      Fourier transform infrared spectroscopy.
AB  - In recent years, fraud detection has become a major priority for food
      authorities, as fraudulent practices can have various economic and safety
      consequences. This work explores ways of identifying frozen-then-thawed minced
      beef labeled as fresh in a rapid, large-scale and cost-effective way. For this
      reason, freshly-ground beef was purchased from seven separate shops at different
      times, divided in fifteen portions and placed in Petri dishes. Multi-spectral
      images and FTIR spectra of the first five were immediately acquired while the
      remaining were frozen (-20 degrees C) and stored for 7 and 32days (5 samples for
      each time interval). Samples were thawed and subsequently subjected to similar
      data acquisition. In total, 105 multispectral images and FTIR spectra were
      collected which were further analyzed using partial least-squares discriminant
      analysis and support vector machines. Two meat batches (30 samples) were reserved
      for independent validation and the remaining five batches were divided in
      training and test set (75 samples). Results showed 100% overall correct
      classification for test and external validation MSI data, while FTIR data yielded
      93.3 and 96.7% overall correct classification for FTIR test set and external
      validation set respectively.

PMID- 29032279
TI  - Colonoscopy-induced right superior rectal artery tear: A case report.
AB  - INTRODUCTION: Colonoscopy is a well-accepted procedure applied worldwide in
      diagnosis and management of colon lesions. The incidence of reported
      complications is not rare. PRESENTATION: A 79-year-old man with postcolonoscopy
      intraperitoneal bleeding secondary to superior rectal artery injury. He received
      computer tomogram and angiogram study to confirmed bleeder from right superior
      rectal artery and subsequently managed with embolization and operation.
      DISCUSSION: This is the second case report in the literatures of mesentery tear
      and the first case with massive hemoperitoneum. CONCLUSION: Identification and
      careful evaluation are crucial for successful diagnosis and treatment in cases
      such as this after colonoscopy.

PMID- 29032280
TI  - Carotid artery stenosis and PERI-operative stroke in cardiac surgery. A bridge
      between heart and brain.

PMID- 29032281
TI  - Differences in mother-to-infant bonding according to type of C-section: Elective
      versus unplanned.
AB  - : Aim To compare the mother-to-infant bond of mothers who gave birth by elective
      C-section versus urgent C-section in the first 48-72h of life and 10-12weeks
      after delivery. METHODS: This is a cohort prospective study of women giving birth
      by C-section. 48-72h after delivery, sociodemographic variables were collected,
      Mother-to-Infant Bonding Scale and newborn's response to separation test were
      performed. 10-12weeks after delivery Mother-to-Infant Bonding Scale and questions
      about baby's feeding were completed. RESULTS: A total of 116 dyads were
      recruited, 58 in each group. No significant differences between the two C
      sections in bonding, newborn response to separation or type of feeding were
      observed at any time points. However, those dyads presenting with an abnormal
      bond at time 1 had more frequently an abnormal bond at time 2 (50% versus 8.1%,
      p=0.000). CONCLUSIONS: No differences in mother-to-infant bond were found
      according to type of C-section.

PMID- 29032283
TI  - Extraskeletal Osteosarcoma of the Hand.
AB  - Extraskeletal osteosarcoma is a rare disease that uncommonly affects the upper
      extremity. A 46-year-old African American man presented for evaluation of a right
      middle finger mass. Excisional biopsy demonstrated extraskeletal osteosarcoma of
      the soft tissues. We performed a transmetacarpal ray resection.

PMID- 29032284
TI  - Mycobacterium longobardum Infection in the Hand.
AB  - Mycobacterium longobardum is a slow-growing, nontuberculous mycobacterium that
      was first characterized in 2012. We report a case of M. longobardum infection in
      the right middle finger of a diabetic man. He underwent surgery for a presumed
      diagnosis of an epidermal inclusion cyst. Molecular diagnosis of the surgical
      specimens demonstrated M. longobardum through RNA polymerase beta-subunit
      encoding gene sequencing. After surgery, the patient was treated with antibiotics
      and eventually cured of the infection. To the best of our knowledge, this is only
      the second reported case of a pathogenic M. longobardum infection worldwide and
      the first such case in the hand. The purposes of this case study are to alert
      treating providers to consider nontuberculous mycobacterium infection when an
      inflammatory process persists, discuss signs and symptoms of the disease, and
      provide general treatment guidelines.

PMID- 29032282
TI  - Atypical ductal hyperplasia: Our experience in the management and long term
      clinical follow-up in 71 patients.
AB  - INTRODUCTION: Atypical ductal hyperplasia (ADH) is a high-risk benign lesion
      found in approximately 1-10% of breast biopsies and associated with a variable
      incidence of carcinoma after surgical excision. The main goal of our study is to
      present our experience in the management and long-term follow-up of 71 patients
      with ADH diagnosed on breast biopsy. MATERIALS AND METHODS: Results of 3808
      breast biopsy specimens from 1 January 2000 to 31 December 2005 were analyzed to
      identify all biopsies which resulted in a diagnosis of ADH. The histopathological
      results of the 45 patients who underwent surgery were analyzed. Long-term follow
      up for the remaining patients was carried out. RESULTS: 45 of 71 (63.4%) patients
      with histological diagnosis of ADH on breast biopsy underwent surgery. Definitive
      histological results revealed invasive carcinoma in 7 cases (15.6%), high grade
      Ductal Carcinoma in situ (DCIS) in 10 (22.2%) patients, Lobular Carcinoma in situ
      (LCIS) in 4 cases (8.9%) and benign findings in 24 cases (53.3%). 12 of 71
      (16.9%) patients underwent only long term follow-up; one (8,3%) of these
      developed invasive breast carcinoma after 6 years. CONCLUSION: Atypical ductal
      hyperplasia diagnosed on breast biopsy is associated with a relatively high
      incidence of invasive carcinoma and high grade ductal carcinoma in situ at the
      time of surgical excision. Certain radiological and cytological criteria can be
      used to help determine which patients should forgo surgery and be followed up
      with good results. Long term follow-up is always crucial for patients who have
      not undergone surgery.

PMID- 29032285
TI  - Blue light emitting diodes (LEDs) as an energy source in Chlorella fusca and
      Synechococcus nidulans cultures.
AB  - LEDs have narrow wavelength bands, which can influence microalgae biomass. This
      study pioneers the evaluation of blue LEDs as an energy source in Chlorella fusca
      and Synechococcus nidulans cultures. Blue LEDs increased the specific growth rate
      in Synechococcus nidulans LEB 115 cultures by 80% compared to the standard light
      used in indoor cultivations. Moreover, blue LEDs also induced lipid accumulation
      in Chlorella fusca LEB 111 cells, yielding concentrations of this bioproduct of
      up to 23% (ww-1). The chlorophylls and carotenoids were photostimulated
      proportionally to the LED light intensity. When the intensity of the blue LEDs
      was increased from 50 to 150MUmolm-2s-1, the biomass accumulated up to 4.5 and
      2.4 times more chlorophylls and carotenoids, respectively. The potential of blue
      LEDs as an alternative environmentally friendly light source to stimulate biomass
      and metabolite production for different purposes was demonstrated.

PMID- 29032286
TI  - Difference or delay? A comparison of Bayley-III Cognition item scores of young
      children with and without developmental disabilities.
AB  - The "difference or delay paradigm" focuses on the question of whether children
      with developmental disabilities (DD) develop in a way that is only delayed,
      compared to typically developing children, or also qualitatively different. The
      current study aimed to examine whether qualitative differences exist in cognitive
      development of young children with and without DD on the basis of item scores on
      the Dutch Bayley-III Cognition scale. Differential item functioning was
      identified for 15 of the 91 items. The presence of DD was related to a higher
      number of Guttman errors, hinting at more deviation in the order of skill
      development. An interaction between group (i.e., with or without DD) and
      developmental quotient appeared to predict the number of Guttman errors. DD was
      related to a higher number of Guttman errors for the whole range of developmental
      quotients; children with DD with a small developmental quotient had the highest
      number. Combined, the results mean that qualitative differences in development
      are not to be excluded, especially in cases of severe developmental disabilities.
      When using the Bayley-III in daily practice, the possibility needs to be taken
      into account that the instruments' assumption of a fixed order in skill
      development does not hold.

PMID- 29032287
TI  - Adaptation of the MABC-2 Test (Age Band 2) for children with low vision.
AB  - BACKGROUND: The tools used to assess motor performance in children with low
      vision often have no validity and reliability data concerning this population and
      use non-standardized modifications. Adaptations of these tools could help to
      identify motor problems and mitigate their effects. AIM: To assess aspects of
      validity and reliability in an adaptation of the Movement ABC-2 Test (MABC-2) for
      children with low vision. METHODS AND PROCEDURES: The research was undertaken in
      two stages: 1) application of the original MABC-2 to 10 children with low vision,
      adaptation and pilot test; 2) administration and re-administration of the adapted
      MABC-2 in 30 children with low vision. Inter-rater reliability and test-retest
      reliability were assessed with an intraclass correlation coefficient and Kappa
      index; internal consistency was assessed with Cronbach's alpha. OUTCOMES AND
      RESULTS: Substantial to almost perfect inter-rater reliability was found between
      the component standard scores and a reasonable to excellent concordance rate in
      the classification of movement difficulty. The adapted tool has moderate internal
      consistency. CONCLUSIONS AND IMPLICATIONS: The adapted MABC-2 Test has improved
      the assessment of motor performance in children with low vision.

PMID- 29032288
TI  - Addressing social skills deficits in adults with Williams syndrome.
AB  - BACKGROUND: Individuals with Williams syndrome (WS) are hypersocial; yet, they
      experience social difficulties and trouble with relationships. This report
      summarizes findings from three studies examining the social functioning of adults
      with WS and the feasibility of a social skills training program for adults with
      WS (SSTP-WS) through the examination of performance on initial lesson plans.
      METHOD: Study 1: 114 parents of adults with WS completed the Social
      Responsiveness Scale-2. Study 2: 10 adults with WS and 12 of their parents
      participated in focus groups to further describe the deficits identified in Study
      1 and to discuss a SSTP-WS. Study 3: 30 adults with WS were randomly assigned to
      2 lessons on either conversations or relationships and pre-post change in social
      skills knowledge was assessed. RESULTS: Study 1 indicates adults with WS
      experience severe social impairments in social cognition, and mild-moderate
      impairments in social awareness and social communication. Qualitative results in
      Study 2 indicate a SSTP-WS should address conversation skills and relationships.
      In Study 3, participants showed gains in social skills knowledge following
      completion of lessons. IMPLICATIONS: A SSTP-WS may be beneficial for adults with
      WS. Future research should describe the social needs of individuals with WS at
      different ages and should further develop a SSTP-WS.

PMID- 29032289
TI  - Exploration of body perception and body dissatisfaction in young adults with
      intellectual disability.
AB  - BACKGROUND: People with intellectual disability (ID) are more likely to be
      overweight or obese. Research has shown that body dissatisfaction is a key factor
      in influencing unhealthy eating behaviour. More evidence is needed relating to
      how people with ID perceive their bodies in order to provide effectively targeted
      weight management programmes. AIMS: This study aimed to investigate whether
      people with ID have concepts for underweight, overweight and healthyweight, and
      whether they can apply these concepts to themselves. It also aimed to explore
      body perception bias through comparison of perceived self to independent figure
      ratings, and body dissatisfaction through perceived-ideal body discrepancy
      measurement and a series of open-ended questions. METHOD: Mixed methodology was
      used to explore body perception and body dissatisfaction in 40 young adults with
      ID compared to 48 individuals without ID. The Stunkard Figure Rating Scale
      assessed how participants would like to look, and their concepts of weight
      categories. RESULTS: Young adults with ID tend to hold positive beliefs about
      their bodies. Females with ID were likely to underestimate their body size.
      Individuals with ID understood what is meant by 'overweight', 'healthy-weight'
      and 'underweight' although these concepts were different to those without ID.
      Individuals with ID were unable to accurately apply these body size categories to
      themselves. CONCLUSION: These findings suggest that individuals with ID will
      first need support to understand how concepts of body size apply to themselves in
      order to facilitate weight management.

PMID- 29032291
TI  - Impact of an osteoporosis specialized unit on bone health in breast cancer
      survivals treated with aromatase inhibitors.
AB  - OBJECTIVE: Considering the increased fracture risk in early breast cancer
      patients treated with aromatase inhibitors (AI), we assessed the impact of a
      preventive intervention conducted by a specialized osteoporosis unit on bone
      health at AI treatment start. MATERIAL AND METHODS: Retrospective cohort of
      postmenopausal women who started treatment with AI after breast cancer
      surgical/chemotherapy treatment and were referred to the osteoporosis unit for a
      comprehensive assessment of bone health. Bone densitometry and fracture screening
      by plain X-ray were performed at the baseline visit and once a year for 5 years.
      RESULTS: The final record included 130 patients. At AI treatment start, 49% had
      at least one high-risk factor for fractures, 55% had osteopenia, and 39%
      osteoporosis. Based on the baseline assessment, 79% of patients initiated
      treatment with bisphosphonates, 88% with calcium, and 79% with vitamin D. After a
      median of 65 (50-77) months, 4% developed osteopenia or osteoporosis, and 14%
      improved their densitometric diagnosis. Fifteen fractures were recorded in 11
      (8.5%) patients, all of them receiving preventive treatment (10 with
      bisphosphonates). During the follow-up period, patients with one or more high
      risk factors for fracture showed a greater frequency of fractures (15% vs. 3%)
      and experienced the first fracture earlier than those without high-risk factors
      (mean of 99 and 102 months, respectively; P=0.023). CONCLUSIONS: The preventive
      intervention of a specialized unit at the start of AI treatment in breast cancer
      survivors allows the identification of patients with high fracture risk and may
      contribute to preventing bone events in these patients.

PMID- 29032290
TI  - Inferential language use by youth with Down syndrome during narration.
AB  - We examined inferential language use by youth with Down syndrome (DS) in the
      context of narrative storytelling relative to younger typically developing (TD)
      children and same-aged peers with fragile X syndrome (FXS) matched on nonverbal
      cognitive ability level. Participants' narratives were coded for the use of
      different types of inferential language. Participants with DS used
      proportionately less inferential language overall relative to their counterparts
      with TD or FXS, although mean length of utterance accounted for group differences
      observed for the DS-TD group comparison only. Patterns of inferential language
      use varied across inferential subtypes and across participant groups, with mean
      length of utterance playing a significant role in group differences. These
      findings suggest potential syndrome specificity to the DS phenotype regarding
      impairments in inferential language use that can be partially explained by level
      of expressive syntactic ability and should be considered in future research.
      Clinical interventions within the DS population, therefore, should target to some
      extent the use of inferential language and complex sentence structure.

PMID- 29032292
TI  - Glimpses into the transition world: New graduate nurses' written reflections.
AB  - BACKGROUND: This study was born out of our reflections as educators responsible
      for helping new graduate nurses transition into their first year of professional
      practice through a formal education programme. Finding ourselves wondering about
      many of the questions the students raised with us, we set about looking more
      closely at what could be gleaned from the students' experience, captured in their
      written work over the course of a year. OBJECTIVES: To identify the challenges
      and learning experiences revealed in reflective assignments written by new
      graduate nurses undertaking a postgraduate course as part of their transition to
      registered nurse practice. STUDY DESIGN, SETTING AND PARTICIPANTS: Data consisted
      of the written work of two cohorts of students who had completed a postgraduate
      university course as part of their transition to new graduate practice in New
      Zealand. Fifty four reflective essays completed by twenty seven participating
      students were collected and their contents analysed thematically. RESULTS: Five
      key themes were identified. The students' reflections noted individual attributes
      - personal and professional strengths and weaknesses; professional behaviour -
      actions such as engaging help and support, advocating for patients' needs and
      safety and putting their own feelings aside; situational challenges such as
      communication difficulties, both systemic and interpersonal, and the pressure of
      competing demands. Students also identified rewards - results they experienced
      such as achieving the nursing outcomes they desired, and commented on reflection
      as a useful tool. CONCLUSIONS: The findings shed light on the experiences of new
      graduates, and how they fare through this critical phase of career development.
      Challenges relating to the emotional labour of nursing work are particularly
      evident. In addition the reflective essay is shown to be a powerful tool for
      assisting both new graduate nurses and their lecturers to reflect on the learning
      opportunities inherent in current clinical practice environments.

PMID- 29032293
TI  - Facilitating problem-based learning among undergraduate nursing students: A
      qualitative systematic review.
AB  - OBJECTIVES: The purpose of this study was to identify and synthesize the best
      available evidence on the perspective of undergraduate nursing students on
      facilitating elements that contribute to their success with PBL. DESIGN: a
      qualitative systematic review of the literature according to meta-aggregative
      methodology using the JBI SUMARI system was conducted. DATA SOURCES: Data was
      collected across CINAHL, Medline, Embase, Eric, Teacher Reference Center and
      reference lists. RESEARCH METHODS: Out of 378 articles, 101 were retrieved for
      examination and eight were retained after methodological analysis. RESULTS: 51
      findings, matched with a verbatim, were extracted and aggregated in five
      categories: 1) in PBL, the nursing tutor models clinical reasoning and leadership
      skills; 2) the quality of group interactions is critical to the success of
      nursing students with PBL; 3) nursing students go through the process of learning
      with PBL; 4) through PBL, nursing students acquire skills that foster clinical
      reasoning; and 5) when the PBL method is used as intended, nursing students
      understand its purpose and process. These categories were aggregated in two
      syntheses worded as recommendation for practice. CONCLUSIONS: The synthesized
      recommendations are: 1) tutors should be trained to effectively guide the team
      work of undergraduate nursing students along the PBL process in order for them to
      achieve its goal; and 2) nursing students should be securely introduced to PBL
      and experience the development of their clinical reasoning through PBL. Future
      research should focus on the strategies undergraduate nursing students use to
      succeed with PBL and the effectiveness of PBL in enhancing critical thinking and
      collaboration skills.

PMID- 29032294
TI  - One year double blind study of high vs low frequency subcallosal cingulate
      stimulation for depression.
AB  - Subcallosal Brodmann's Area 25 (Cg25) Deep Brain Stimulation (DBS) is a new
      promising therapy for treatment resistant major depressive disorder (TR-MDD).
      While different DBS stimulating parameters may have an impact on the efficacy and
      safety of the therapy, there is no data to support a protocol for optimal
      stimulation parameters for depression. Here we present a prospective multi-center
      double-blind randomized crossed-over 13-month study that evaluated the effects of
      High (130 Hz) vs Low (20 Hz) frequency Cg25 stimulation for nine patients with TR
      MDD. Four out of nine patients achieved response criteria (>=40% reduction of
      symptom score) compared to mean baseline values at the end of the study. The mean
      percent change of MADRS score showed a similar improvement in the high and low
      frequency stimulation groups after 6 months of stimulation (-15.4 +/- 21.1 and 
      14.7 +/- 21.1 respectively). The mean effect at the end of the second period (6
      months after cross-over) was higher than the first period (first 6 months of
      stimulation) in all patients (-23.4 +/- 19.9 (n = 6 periods) and -13.0 +/- 22 (n
      = 9 periods) respectively). At the end of the second period, the mean percent
      change of the MADRS scores improved more in the high than low frequency groups (
      31.3 +/- 19.3 (n = 4 patients) and -7.7 +/- 10.9 (n = 2 patients) respectively).
      Given the small numbers, detailed statistical analysis is challenging.
      Nonetheless the results of this study suggest that long term high frequency
      stimulation might confer the best results. Larger scale, randomized double blind
      trials are needed in order to evaluate the most effective stimulation parameters.

PMID- 29032296
TI  - Most Gleason 8 Biopsies are Downgraded at Prostatectomy-Does 4 + 4 = 7?
AB  - PURPOSE: Nonrepresentative biopsy sampling of prostate cancers with a biopsy
      Gleason score of 8 can adversely influence decisions regarding androgen
      deprivation in men receiving primary radiation therapy. The frequency of and
      factors associated with downgrading Gleason 8 biopsies at prostatectomy are not
      well known. MATERIALS AND METHODS: We used records from NCDB (National Cancer
      Database), a hospital based registry in the United States, of 72,556 men with
      prostate cancer diagnosed from 2010 to 2013, including 5,474 with Gleason 8
      biopsies and no other high progression risk criteria according to NCCN (National
      Comprehensive Cancer Network(r)) Guidelines(r). The prevalence of Gleason 8
      downgrading was calculated. Generalized estimating equation multivariable
      regression models were used to estimate the prevalence ratios and 95% CIs of
      downgrading by demographic and clinical factors, and evaluate the association of
      Gleason 8 downgrading with cT (clinical T) to pathological T category up staging.
      RESULTS: Of 5,474 Gleason 8 biopsies in men lacking other high progression risk
      criteria 3,263 (60%) were downgraded, changing the progression risk category from
      high to intermediate. A higher prevalence of Gleason 8 downgrading was
      significantly and independently associated with decreasing age, African American
      race, lower cT category, lower prostate specific antigen quartile and certain
      combinations of primary and secondary Gleason grades (3 + 5 greater than 4 + 4
      greater than 5 + 3). Gleason 8 downgrading in cases of cT less than 3 was
      independently and significantly associated with a lower prevalence of up staging
      (prevalence ratio = 0.65, 95% CI 0.61-0.69). CONCLUSIONS: Downgrading Gleason 8
      biopsies is common. Patient evaluation based on Gleason 8 biopsies often results
      in overestimating progression risk and disease extent, which may lead to
      overtreatment.

PMID- 29032295
TI  - Innate sensing of cancer's non-immunologic hallmarks.
AB  - A cancer mass consists of a complex composition of cancer cells, stromal cells,
      endothelial cells and also immune cells, which can represent more than half of
      the cellularity of a solid cancer. These immune cells become activated when they
      sense cancer antigens and stress ligands. Innate immune cells also detect various
      aspects of cellular stress that characterize a growing tumor mass. These key
      hallmarks of cellular stress are also detected by the cancer cell itself. In this
      review, we highlight studies that show that the cancer cell itself could be
      considered an 'innate cell' that senses and reacts to non-immunologic hallmarks
      of cancer, including displaced nucleic acids, proteotoxic stress, oxidative
      stress, and metabolic alterations.

PMID- 29032297
TI  - Postoperative Complications following Primary Penile Inversion Vaginoplasty among
      330 Male-to-Female Transgender Patients.
AB  - PURPOSE: Studies of surgical complications of penile inversion vaginoplasty are
      limited due to small sample sizes. We describe postoperative complications after
      penile inversion vaginoplasty and evaluated age, body mass index and years on
      hormone replacement therapy as risk factors for complications. MATERIALS AND
      METHODS: We retrospectively reviewed the records of male-to-female patients who
      presented for primary penile inversion vaginoplasty to a high volume surgeon
      (MLB) from 2011 to 2015. Complications included granulation tissue, vaginal pain,
      wound separation, labial asymmetry, vaginal stenosis, fistula formation, urinary
      symptoms including spraying stream or dribbling, infection, vaginal fissure or
      vaginal bleeding. We classified complications by Clavien-Dindo grade.
      Multivariable logistic regression was performed to determine the independent
      effects of age, body mass index and hormone replacement therapy on postoperative
      surgical complications. RESULTS: A total of 330 patients presented for primary
      penile inversion vaginoplasty. Median age at surgery was 35 years (range 18 to
      76). Median followup in all patients was 3 months (range 3 to 73). Of the
      patients 95 (28.7%) presented with a postoperative complication. Median time to a
      complication was 4.4 months (IQR 1-11.5). Rectoneovaginal fistulas developed in 3
      patients (0.9%). A total of 30 patients (9.0%) required a second operation. There
      were no complications greater than Clavien-Dindo grade IIIB. Age, body mass index
      and hormone replacement therapy were not associated with complications.
      CONCLUSIONS: Penile inversion vaginoplasty is a relatively safe procedure. Most
      complications due to this surgery develop within the first 4 months
      postoperatively. Age, body mass index and hormone replacement therapy are not
      associated with complications and, thus, they should not dictate the timing of
      surgery.

PMID- 29032298
TI  - Factors and outcomes associated with inpatient cardiac arrest following emergent
      endotracheal intubation.
AB  - BACKGROUND: Inpatient peri-intubation cardiac arrest (PICA) following emergent
      endotracheal intubation (ETI) is an uncommon but potentially preventable type of
      cardiac arrest (CA). Limited published data exist describing factors associated
      with inpatient PICA and patient outcomes. This study identifies risk factors
      associated with PICA among hospitalized patients emergently intubated out of the
      operating room and compares PICA to other types of inpatient CA. METHODS:
      Retrospective case-control study of patients at our institution over a five-year
      period. Cases were defined as inpatients emergently intubated outside of the
      operating room that experienced cardiac arrest within 20min after ETI. The
      control group consisted of inpatients emergently intubated out of the operating
      room without CA. Predictors of PICA were identified through univariate and
      multivariate analysis. Clinical outcomes were compared between PICA and other
      inpatient CAs, identified through a prospectively enrolled CA registry at our
      institution. RESULTS: 29 episodes of PICA occurred over 5 years, accounting for
      5% of all inpatient arrests. Shock index >=1.0, intubation within one hour of
      nursing shift change, and use of succinylcholine were independently associated
      with PICA. Sustained ROSC, survival to discharge, and neurocognitive outcome did
      not differ significantly between groups. CONCLUSION: Patients outcomes following
      PICA were comparable to other causes of inpatient CA. Potentially modifiable
      factors were associated with PICA. Hemodynamic resuscitation, optimized staffing
      strategies, and possible avoidance of succinylcholine were associated with
      decreased risk of PICA. Clinical trials testing targeted strategies to optimize
      peri-intubation care are needed to identify effective interventions to prevent
      this potentially avoidable type of CA.

PMID- 29032299
TI  - Association of antiplatelet therapy with patient outcomes after out-of-hospital
      cardiac arrest.
AB  - BACKGROUND: Cessation of blood flow during out-of-hospital cardiac arrest (OHCA)
      results in microvascular thrombosis, protracted hypoperfusion after return of
      spontaneous circulation and damage to vital organs. We tested the hypothesis that
      pre-arrest antiplatelet and anticoagulant medication use would be associated with
      less post-arrest organ dysfunction and better outcomes. METHODS: We included OHCA
      patients treated from January 2005 to October 2014 at a single academic medical
      center. We combined our prospective OHCA registry of clinical and demographic
      data with a structured chart review to abstract home antiplatelet and
      anticoagulant medications. We fit unadjusted and adjusted regression models to
      test the association of antiplatelet and anticoagulant medication use with early
      post-arrest illness severity, survival and functionally favorable recovery.
      RESULTS: Of 1054 subjects, 295 (28%) were prescribed an antiplatelet agent and
      147 (14%) were prescribed an anticoagulant prior to arrest. In adjusted models,
      antiplatelet agents were associated with lower post-arrest illness severity
      (adjusted OR 0.50 95% CI 0.33-0.77), greater odds of survival to discharge
      (adjusted OR 1.74 95% CI 1.08-2.80) and greater odds favorable functional outcome
      (adjusted OR 2.11 95% CI 1.17-3.79). By contrast, anticoagulation via any agent
      was not associated with illness severity, survival to discharge or favorable
      outcome. CONCLUSION: Preventing intra-arrest and post-arrest microvascular
      thrombosis via antiplatelet agents could represent a novel therapeutic target to
      improve outcomes after OHCA.

PMID- 29032300
TI  - Is digestive cathepsin D the rule in decapod crustaceans?
AB  - Cathepsin D is an aspartic endopetidase with typical characteristics of lysosomal
      enzymes. Cathepsin D activity has been reported in the gastric fluid of clawed
      lobsters where it acts as an extracellular digestive enzyme. Here we investigate
      whether cathepsin D is unique in clawed lobsters or, instead, common in decapod
      crustaceans. Eleven species of decapods belonging to six infraorders were tested
      for cathepsin D activity in the midgut gland, the muscle tissue, the gills, and
      when technically possible, in the gastric fluid. Cathepsin D activity was present
      in the midgut gland of all 11 species and in the gastric fluid from the seven
      species from which samples could be taken. All sampled species showed higher
      activities in the midgut glands than in non-digestive organs and the activity was
      highest in the clawed lobster. Cathepsin D mRNA was obtained from tissue samples
      of midgut gland, muscle, and gills. Analyses of deduced amino acid sequence
      confirmed molecular features of lysosomal cathepsin D and revealed high
      similarity between the enzymes from Astacidea and Caridea on one side, and the
      enzymes from Penaeoidea, Anomura, and Brachyura on the other side. Our results
      support the presence of cathepsin D activity in the midgut glands and in the
      gastric fluids of several decapod species suggesting an extracellular function of
      this lysosomal enzyme. We discuss whether cathepsin D may derive from the
      lysosomal-like vacuoles of the midgut gland B-cells and is released into the
      gastric lumen upon secretion by these cells.

PMID- 29032301
TI  - Formation of asymmetric vesicles via phospholipase D-mediated
      transphosphatidylation.
AB  - Most biomembranes have an asymmetric structure with regard to phospholipid
      distribution between the inner and outer leaflets of the lipid bilayers. Control
      of the asymmetric distribution plays a pivotal role in several cellular functions
      such as intracellular membrane fusion and cell division. The mechanism by which
      membrane asymmetry and its alteration function in these transformation processes
      is not yet clear. To understand the significance of membrane asymmetry on
      trafficking and metabolism of intracellular vesicular components, a system that
      experimentally reproduces the asymmetric nature of biomembranes is essential.
      Here, we succeeded in obtaining asymmetric vesicles by means of
      transphosphatidylation reactions with phospholipase D (PLD), which acts
      exclusively on phosphatidylcholine (PC) present in the outer leaflet of vesicles.
      By treating PC vesicles with PLD in the presence of 1.7M serine and 0.3M
      ethanolamine, we obtained asymmetric vesicles that are topologically similar to
      intracellular vesicles containing phosphatidylserine and phosphatidylethanolamine
      in the cytosolic leaflet. PLD and other unwanted compounds could be removed by
      trypsin digestion followed by dialysis. Our established technique has a great
      advantage over conventional methods in that asymmetric vesicles can be provided
      at high yield and high efficiency, which is requisite for most physicochemical
      assays.

PMID- 29032302
TI  - Synthetic heparin and heparan sulfate: probes in defining biological functions.
AB  - Heparin and heparan sulfate are glycosaminoglycans that modulate numerous
      biological processes. The desire to capture the structural diversity responsible
      for their functions provides notable issues during synthesis, including site
      selective sulfonation, stereoselective glycosylation and the sheer number of
      probable targets at hand. With current advances in synthetic approaches,
      carbohydrate chemists generate these complex targets by chemical and enzymatic
      methods. Fondaparinux and a number of polysaccharides have been synthesized to
      probe anticoagulation and other biological functions. Moreover, a trove of
      structural information could be obtained by many analytical methods, which
      provide hints to the potential protein-binding sequences within the sugar chain.
      Further structure-activity relationship studies help unveil the secrets of the
      heparin/heparan sulfate code, providing potential candidates for drug
      development.

PMID- 29032303
TI  - Current strategies to streamline pharmacotherapy for older adults.
AB  - Although the term "personalized medicine" has been associated in many cases with
      pharmacogenomics, its definition embraces the use of specific biomarkers and
      covariates to help in the selection of medical treatments and procedures which
      are best for each patient. While several efforts have been performed for the
      tailored selection of therapies and dosing regimens in the general population,
      developing personalized medicine initiatives for elderly patients remains
      understudied. The personalized drug therapy for older patients requires the
      consideration of anatomical, physiological and functional alterations in a
      multimorbid setting requiring multiple medications. The present review focuses on
      currently employed qualitative and quantitative precision medicine approaches for
      elderly patients and discusses some of the associated challenges and limitations.
      Furthermore, the use of and confidence in physiologically-based approaches for
      optimal dose selection in this understudied yet clinically important patient
      population will be highlighted and discussed.

PMID- 29032304
TI  - Heterocyclic homoprostanoid derivative attenuates monoarthritis in rats: An in
      vitro and in vivo preclinical paradigm.
AB  - From our lab, among the nineteen heterocyclic homoprostanoids (HHPs), three
      derivatives (compounds 3, 3b and 3c) exerted antioxidant and anti-inflammatory
      activity. Present study is an extension of the earlier work, and, is designed to
      establish their therapeutic potential in monoarthritis in rats. In addition,
      their possible mechanism of action would be investigated. A battery of in vitro
      tests such as lipopolysaccharide (LPS)-induced nitrite (NO)/reactive oxygen
      species (ROS) and NO/interleukin (IL)-6 generation in murine macrophages and
      whole blood (WhB), respectively were conducted. Later, in vitro cyclooxygenase
      (COX) enzyme inhibitory activity was also evaluated. All the tested compounds
      showed comparable efficacy against ROS and NO in LPS-stimulated murine
      macrophages. However, compound 3 did not exert inhibitory effect on LPS-induced
      NO/IL-6 generation in WhB assay. Compounds (3b and 3c) inhibited the NO
      generation in LPS-stimulated WhB. However, only compound 3b reversed the raised
      IL-6 levels in this assay. None of the test compounds inhibited COX iso-enzymes
      in the in vitro assay. All three HHPs showed comparable efficacy against
      carrageenan-induced paw inflammation. However, none of them exhibited any dose
      dependent effect in this model. Based upon previous reports, compound 3c was
      explored against adjuvant-induced monoarthritis (AIA) in male Sprague-Dawley
      rats, where it exerted promising therapeutic effect. In addition to radiological
      and histological examinations of tibio-tarsal joint, various parameters such as
      chronic inflammation/pain, clinical score, interleukin (IL)-6 levels and complete
      blood cell profile were evaluated in AIA rats. Chronic treatment with 3c halted
      the disease progression in rats, improved the overall health of animals, as
      demonstrated by haematological, clinical scoring and joint examinations
      (radiological and histopathological). Inhibitory effect on elevated IL-6 in AIA
      rats suggested the possible mechanism of 3c on cytokine signalling. Overall, the
      study supports the anti-arthritic potential of compound 3c.

PMID- 29032305
TI  - Physicochemical pharmacokinetics as an optimization tool for generic development:
      A case study.
AB  - In spite of the fact that dissolution time profiles of 250mg ursodeoxycholic acid
      (UCDA) capsules developed by Sponsor and 250mg hard capsules produced by
      Ursofalk(r), Dr. Falk Pharma GmbH, indicated similarity (f2=60.6), a
      bioavailability study indicated unexpected differences in the formulations. To
      find an explanation of the in vivo performance of the compared formulations, the
      dissolution profiles were analyzed using a novel dissolution theory considering:
      The dissolution model was applied to the measured data using SADAPT. Despite Cmax
      and AUC values showing higher values after administration of the test product, a
      reduction of UDCA particle size for the test formulation was suggested for
      reformulation. The decision was based on the strongly pH-dependent UDCA
      solubility, formation of insoluble crystals at low pH condition and the known
      high pH fluctuations ranging from pH1 to 8 in empty stomach. The performed
      reformulation led to increased dissolution rate of the test product and to a
      positive bioequivalence study which compared the reformulated test generic
      formulation with two reference products purchased from two highly regulated
      markets.

PMID- 29032306
TI  - Implementing the additional strength biowaiver for generics: EMA recommended
      approaches and challenges for a US-FDA submission.
AB  - This review describes the EMA requirements on biowaivers for additional strengths
      of immediate release and modified release oral solid dosage forms focused on
      generic applications and highlights the challenges for a simultaneous EMA and FDA
      submission. Some specificities of the current EMA guidelines are compared with
      the current FDA Guidance for Industry, with a special focus on the strength to be
      investigated in vivo, formulation suitability for biowaiver, and optimizing
      dissolution studies for additional strength biowaivers. In Europe, the same
      principles applied for generics may be considered for deriving the biowaivers for
      innovator products. Several case studies are presented to illustrate the
      challenges of applying for additional strength biowaivers in EMA and FDA
      simultaneously.

PMID- 29032307
TI  - Biomechanical properties of different techniques used in vitro for suturing mid
      substance Achilles tendon ruptures.
AB  - BACKGROUND: The Dresden technique preserves the paratenon during Achilles tendon
      repair and may improve the plantarflexor mechanism when combined with
      mobilization during early rehabilitation. However, the surgical repair design for
      Achilles tendon ruptures can affect rates of re-rupture or lengthening.
      Therefore, the aim of this study was to determine the biomechanical properties of
      the Krackow, Double-Kessler, Double-Dresden, and Triple-Dresden techniques used
      for repairing mid-substance Achilles tendon ruptures during cyclical and maximum
      traction. METHODS: Sixty mid-substance bovine tendons repaired after transverse
      rupturing were divided randomly into four groups by repair technique: Krackow,
      Double-Kessler, Double-Dresden, and Triple-Dresden. Cyclical tractions of 4.7,
      5.8, 7.9, and 11.7mm (equivalent to 5 degrees , 8 degrees , 10 degrees , and 15
      degrees  of dorsal flexion, respectively) were applied to determine gapping,
      tensile strength, nominal suture stress, repair deformation, and specimens with
      clinical failure (gap>5mm). Maximal traction was applied to measure maximum
      strength and failure type (i.e. suture, knot, or tendon). FINDINGS: The Triple
      Dresden technique resulted in decreased gapping, nominal suture stress, repair
      deformation, and quantity of specimens with clinical failure as compared to the
      other techniques. Furthermore, Triple-Dresden tendons showed greater comparative
      tensile and maximum strength. During maximal traction testing, this technique
      presented tendon failure, whereas the Krackow, Double-Kessler, and Double-Dresden
      techniques had suture failures. INTERPRETATION: Triple-Dresden repair results in
      better cyclical and maximum traction strengths, suggesting that this technique
      might be more appropriate when performing early mobilization after mid-substance
      Achilles tendon rupture repair.

PMID- 29032308
TI  - Comparison of mode of failure between primary and revision total knee
      arthroplasties.
AB  - INTRODUCTION: Cognizance of common reasons for failure in primary and revision
      TKA, together with their time course, facilitates prevention. However, there have
      been few reports specifically comparing modes of failure for primary vs. revision
      TKA using a single prosthesis. The goal of the study was to compare the survival
      rates, modes of failure, and time periods associated with each mode of failure,
      of primary vs. revision TKA. HYPOTHESIS: The survival rates, modes of failure,
      time period for each mode of failure, and risk factors would differ between
      primary and revision TKA. MATERIAL AND METHODS: Data from a consecutive cohort
      comprising 1606 knees (1174 patients) of primary TKA patients, and 258 knees (224
      patients) of revision TKA patients, in all of whom surgery involved a P.F.C(r)
      prosthesis (Depuy, Johnson & Johnson, Warsaw, IN), was retrospectively reviewed.
      The mean follow-up periods of primary and revision TKAs were 9.2 and 9.8 years,
      respectively. RESULTS: The average 10- and 15-year survival rates for primary TKA
      were 96.7% (CI 95%,+/-0.7%) and 85.4% (CI 95%,+/-2.0%), and for revision TKA
      91.4% (CI 95%,+/-2.5%) and 80.5% (CI 95%,+/-4.5%). Common modes of failure
      included polyethylene wear, loosening, and infection. The most common mode of
      failure was polyethylene wear in primary TKA, and infection in revision TKA. The
      mean periods (i.e., latencies) of polyethylene wear and loosening did not differ
      between primary and revision TKAs, but the mean period of infection was
      significantly longer for revision TKA (1.2 vs. 4.8 years, P=0.003). DISCUSSION:
      Survival rates decreased with time, particularly more than 10 years post-surgery,
      for both primary and revision TKAs. Continuous efforts are required to prevent
      and detect the various modes of failure during long-term follow-up. Greater
      attention is necessary to detect late infection-induced failure following
      revision TKA. LEVEL OF EVIDENCE: Case-control study, Level III.

PMID- 29032309
TI  - Anterior cruciate ligament revision with Achilles tendon allograft in young
      athletes.
AB  - BACKGROUND: Return to sport after revision ACL reconstruction is a controversial
      topic, several studies reported the results of different techniques and graft in
      sportsman, presenting an incredibly wide range of return to the same pre-injury
      activity level, from 0% to 100%. The purpose of this study was to evaluate the
      clinical outcomes and return to sport rate in young athletes after non anatomic
      double-bundle revision ACL reconstruction with Achilles allograft. HYPOTHESIS:
      The present revision technique was effective in terms of stability, return to
      sport and functional outcomes. MATERIAL AND METHODS: All the athletes undergone
      Revision ACL reconstruction with non-irradiated Achilles tendon allograft with a
      non-anatomical double-bundle technique were included in the study. A split
      Achilles tendon allograft was used to reproduce the anteromedial (AM) bundle
      using the over-the-top position, while the posterolateral (PL) bundle was
      reconstructed through a femoral tunnel located in the anatomical PL footprint.
      Sport activity, knee function with Lysholm score, knee laxity and re-injury or re
      operations were evaluated. RESULTS: Twenty-six athletes (23 males, three females)
      with a mean age of 23.4+/-3.6 years were evaluated at a mean follow-up of 6.0+/
      1.6 years. Overall 69% of patients returned to sport both at elite (44%) or
      county level (56%) after a mean 6.7+/-1.5 (3-9 range) months. The mean Lysholm
      score showed a significant improvement from 64.4+/-8.1 at pre-operative status to
      83.8+/-11.3 at final follow-up (P<.0001). Seven patients (30%) were rated as
      excellent, nine (39%) as good, five (22%) as fair and 2 (9%) as poor. Three
      patients (12%) experienced a further graft rupture after a mean 2.6 years, (3.5
      months-48 months range) and two had >5mm side-to-side difference at KT-1000.
      Therefore, the overall survival rate at mean six years follow-up was 81%.
      CONCLUSION: The ACL revision with a double-bundle technique using Achilles tendon
      allograft was successful in 81% of athletes at six years mean follow-up. TYPE OF
      STUDY AND LEVEL OF EVIDENCE: Retrospective case series, level IV.

PMID- 29032310
TI  - Building addiction recovery capital through online participation in a recovery
      community.
AB  - RATIONALE: This study examines how online participation in a community of
      recovery contributes to personal journeys of recovery. It investigates whether
      recovery capital building - as indicated by increased levels and quality of
      online social interactions - and markers of positive identity development predict
      retention in a recovery program designed around fostering community involvement
      for early stage recovery addicts. HYPOTHESES: It was predicted that online
      participation on the group's Facebook page and positive identity development are
      associated to retention in the program. METHODS: To map how participants interact
      online, social network analysis (SNA) based on naturally occurring online data (N
      = 609) on the Facebook page of a recovery community was conducted. Computerised
      linguistic analyses evaluated sentiment of the textual data (capturing social
      identity markers). Linear regression analyses evaluated whether indicators of
      recovery capital predict program retention. To illustrate the findings in the
      context of the specific recovery community, presented are two case studies of key
      participants who moved from the periphery to the centre of the social network. By
      conducting in-depth interviews with these participants, personal experiences of
      engagement in the online community of group members who have undergone the most
      significant changes since joining the community are explored. RESULTS: Retention
      in the program was determined by a) the number of comment 'likes' and all 'likes'
      received on the Facebook page; b) position in the social network (degree of
      centrality); and c) linguistic content around group identity and achievement.
      CONCLUSION: Positive online interactions between members of recovery communities
      support the recovery process through helping participants to develop recovery
      capital that binds them to groups supportive of positive change.

PMID- 29032311
TI  - A hybrid wavelet de-noising and Rank-Set Pair Analysis approach for forecasting
      hydro-meteorological time series.
AB  - Accurate, fast forecasting of hydro-meteorological time series is presently a
      major challenge in drought and flood mitigation. This paper proposes a hybrid
      approach, wavelet de-noising (WD) and Rank-Set Pair Analysis (RSPA), that takes
      full advantage of a combination of the two approaches to improve forecasts of
      hydro-meteorological time series. WD allows decomposition and reconstruction of a
      time series by the wavelet transform, and hence separation of the noise from the
      original series. RSPA, a more reliable and efficient version of Set Pair
      Analysis, is integrated with WD to form the hybrid WD-RSPA approach. Two types of
      hydro-meteorological data sets with different characteristics and different
      levels of human influences at some representative stations are used to illustrate
      the WD-RSPA approach. The approach is also compared to three other generic
      methods: the conventional Auto Regressive Integrated Moving Average (ARIMA)
      method, Artificial Neural Networks (ANNs) (BP-error Back Propagation, MLP
      Multilayer Perceptron and RBF-Radial Basis Function), and RSPA alone. Nine error
      metrics are used to evaluate the model performance. Compared to three other
      generic methods, the results generated by WD-REPA model presented invariably
      smaller error measures which means the forecasting capability of the WD-REPA
      model is better than other models. The results show that WD-RSPA is accurate,
      feasible, and effective. In particular, WD-RSPA is found to be the best among the
      various generic methods compared in this paper, even when the extreme events are
      included within a time series.

PMID- 29032313
TI  - Influence of platform diameter in the reliability and failure mode of extra-short
      dental implants.
AB  - PURPOSE: To evaluate the influence of implant diameter in the reliability and
      failure mode of extra-short dental implants. MATERIALS AND METHODS: Sixty-three
      extra-short implants (5mm-length) were allocated into three groups according to
      platform diameter: O4.0-mm, O5.0-mm, and O6.0-mm (21 per group). Identical
      abutments were torqued to the implants and standardized crowns cemented. Three
      samples of each group were subjected to single-load to failure (SLF) to allow the
      design of the step-stress profiles, and the remaining 18 were subjected to step
      stress accelerated life-testing (SSALT) in water. The use level probability
      Weibull curves, and the reliability (probability of survival) for a mission of
      100,000 cycles at 100MPa, 200MPa, and 300MPa were calculated. Failed samples were
      characterized in scanning electron microscopy for fractographic inspection.
      RESULTS: No significant difference was observed for reliability regarding implant
      diameter for all loading missions. At 100MPa load, all groups showed reliability
      higher than 99%. A significant decreased reliability was observed for all groups
      when 200 and 300MPa missions were simulated, regardless of implant diameter. At
      300MPa load, the reliability was 0%, 0%, and 5.24%, for O4.0mm, O5.0mm, and
      O6.0mm, respectively. The mean beta (beta) values were lower than 0.55 indicating
      that failures were most likely influenced by materials strength, rather than
      damage accumulation. The O6.0mm implant showed significantly higher
      characteristic stress (eta = 1,100.91MPa) than O4.0mm (1,030.25MPa) and O5.0mm
      implant (eta = 1,012.97MPa). Weibull modulus for O6.0-mm implant was m = 7.41, m
      = 14.65 for O4.0mm, and m = 11.64 for O5.0mm. The chief failure mode was abutment
      fracture in all groups. CONCLUSIONS: The implant diameter did not influence the
      reliability and failure mode of 5mm extra-short implants.

PMID- 29032312
TI  - Advanced oxidation protein products induce S-phase arrest of hepatocytes via the
      ROS-dependent, beta-catenin-CDK2-mediated pathway.
AB  - Liver regeneration has important clinical importance in the setting of partial
      hepatectomy (PH). Following PH, quiescent hepatocytes can reenter cell cycle to
      restore liver mass. Hepatocyte cell cycle progression, as the basic motivations
      of liver regeneration, can be disrupted by multiple pathological factors such as
      oxidative stress. This study aimed to evaluate the role of advanced oxidation
      protein products (AOPP) in S-phase arrest in hepatocytes. Serum AOPP level were
      measured during the perioperative period of PH in 33 patients with hepatocellular
      carcinoma (HCC). Normal Sprague Dawley rats, human and murine liver cell line (HL
      7702 and AML-12) were challenged with AOPP prepared by incubation of rat serum
      albumin (RSA) with hypochlorous acid, and the effect of AOPP on hepatocytes cell
      cycle progression and liver regeneration was studied after PH. AOPP levels were
      increased following partial hepatectomy (PH) in patients with primary liver
      cancer. AOPP treatment impaired liver regeneration in rats following 70% partial
      hepatectomy. S-phase arrest was induced by AOPP administration in hepatocytes
      derived from the remnant liver at controlled times following partial hepatectomy
      in rats, and in HL-7702 and AML-12 cells. The effect of AOPP on hepatocyte S
      phase arrest was mainly mediated by a nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase-dependent reactive oxygen species (ROS) generation,
      downregulation of downstream beta-catenin signaling and decreased cyclin
      dependent kinase 2 (CDK2) expression, which inhibited S-phase progression in
      hepatocytes. This study provides preliminary evidence that AOPP can induce S
      phase arrest in hepatocytes via the ROS-dependent, beta-catenin-CDK2-mediated
      pathway. These findings suggest a novel pathogenic role of AOPP contributing to
      the impaired liver regeneration and may provide the basis for developing new
      strategies to improve liver regeneration in patients undergoing PH.

PMID- 29032314
TI  - Remodeling of arterial wall: Response to changes in both blood flow and blood
      pressure.
AB  - Many studies have been performed on arterial responses to chronic changes in
      blood flow (BF) and blood pressure (BP). However, little is known about the
      effects of simultaneous changes in BF and BP. The present study was carried out
      to know biomechanical responses of arterial wall to the combination of increased
      BP, i.e. hypertension (HT), with lower or higher BF than normal, and the results
      were compared with those observed under normal BP, i.e. normotension (NT),
      combined with these BF conditions. Eight weeks old rats were subjected to BF
      and/or BP changes for 8 weeks until 16 weeks of age. Systemic HT was induced by
      the constriction of one of the renal arteries (Goldblatt HT), while BF in the CCA
      was reduced and increased by the constriction of the ipsilateral CCA and the
      ligation of the contralateral CCA, respectively. The internal diameter of the
      target CCA was significantly larger in higher BF groups than in lower BF ones
      irrespective of HT. Wall shear stress (WSS) was normalized by such compensatory
      changes in the diameter. Wall thickness was significantly larger in HT rats than
      in NT ones regardless of BF, and the wall hypertrophy contributed to restore wall
      hoop stress to normal level. Basal vascular tone, arterial stiffness, and wall
      elastic modulus were significantly larger in HT than in NT independently of BF
      changes. However, only in HT/lower BF group, WSS and vascular smooth muscle
      activated vascular contraction were smaller than in the other groups, possibly
      because of wall hypertrophy induced by HT.

PMID- 29032315
TI  - Influence of interface conditions on the response of transversely isotropic multi
      layered medium by impact load.
AB  - Multi-layered media are one of the most common phenomena in natural or artificial
      surroundings, and it is considered as a good candidates for biomedical
      applications. The transversely isotropic characteristic of materials have been
      widely recognized in elastic multi-layered media. Furthermore, interface
      conditions between transversely isotropic elastic multi-layered medium layers
      plays an important role in the medium's performance. Despite many numerical
      approaches in these analyses, very few theoretical methods are available in
      dealing with these two important issues. This study presents a method to compute
      the response of transversely isotropic elastic multi-layered medium subjected to
      the impact load, i.e. falling weight deflectometer load (FWD) load, when
      interfacial conditions are considered. Details of the mathematical derivation,
      implementation and verification of the proposed analytical solution are
      presented. The absence of positive exponential functions in the solution leads to
      a considerable improvement in computation efficiency and stability. Subsequent
      numerical results demonstrate that both transverse isotropy and interface
      conditions could substantially contribute to the responses of the elastic multi
      layered medium.

PMID- 29032316
TI  - Fiber-reinforced silicone for tracheobronchial stents: An experimental study.
AB  - A trachea is a tubular structure composed of smooth muscle that is reinforced
      with cartilage rings. Some diseases can cause sagging in smooth muscle and
      cartilaginous tissue. The end result is reduction (narrowing) of the trachea
      diameter. A solution to this problem is the use of tracheal stents, which are
      small tubular devices made of silicone. One is inserted into the trachea to
      prevent or correct its constriction. The purpose of tracheal stent use is to
      maintain cartilage support that would otherwise be lost in the airway. Current
      tracheal stent models present limitations in terms of shape and characteristics
      of the silicone used in their production. One of the most important is the large
      thickness of the wall, which makes its placement difficult; this mainly applies
      to pediatric patients. The wall thickness of the stent is closely related to the
      mechanical properties of the material. This study aims to test the reinforcement
      of silicone with three kinds of fibers, and then stents that were produced using
      fiber with the best compressive strength characteristics. Silicone samples were
      reinforced with polypropylene (PP), polyamide (PA), and carbon fiber (CF) at
      concentrations of 2% and 4% (vol%), which then underwent tensile strength and
      Shore A hardness testing. Samples with fiber showed good characteristics; surface
      analyses were carried out and they were used to produce stents with an internal
      diameter of 11 or 13mm and a length of 50mm. Stents underwent compression tests
      for qualitative evaluation. Samples with 2% and 4% CF blends showed the best
      mechanical performance, and they were used to produce stents. These samples
      presented similar compressive strengths at low deformation, but stents with a 4%
      CF blend exhibited improved compressive strength at deformations greater than 30
      50% of their diameter (P <= 0.05). The addition of 2% and 4% CF blends conferred
      greater mechanical strength and resistance to the silicone matrix. This is
      particularly true at low deformation, which is the condition where the stent is
      used when implanted. In the finite element compression strength tests, the stent
      composite showed greater compression strength with the addition of fiber, and the
      results were in accordance with mechanical compression tests performed on the
      stents. In vivo tests showed that, after 30 days of post-implantation in sheep
      trachea, an inflammatory process occurred in the region of the trachea in contact
      with the stent composite and with the stent without fiber (WF). This response is
      a common process during the first few days of implantation.

PMID- 29032317
TI  - Predictors of short-term change after a brief alcohol intervention for mandated
      college drinkers.
AB  - OBJECTIVE: Brief motivational interventions (BMIs) reduce problematic drinking
      for some, but not all, college students. Identifying those students who are less
      responsive can help to guide intervention refinement. Therefore, we examined
      demographic, personality, and cognitive factors hypothesized to influence change
      after a BMI. METHOD: Students mandated for intervention following a campus
      alcohol violation (N=568; 28% female, 38% freshmen) completed a baseline
      assessment, then received a BMI, and then completed a 1-month follow-up. At both
      assessments, alcohol use (i.e., drinks per week, typical BAC, binge frequency)
      and alcohol-related problems were measured. RESULTS: Latent change score analyses
      revealed significant decrease in both alcohol use and problems 1month after the
      BMI. In the final model that predicted change in alcohol use, four factors (male
      sex, a "fun seeking" disposition, more perceived costs and fewer perceived
      benefits of change) predicted smaller decreases in alcohol use over time. In the
      final model that predicted change in alcohol-related problems, three factors
      (stronger beliefs about the centrality of alcohol to college life, more perceived
      costs and fewer perceived benefits of change) predicted smaller decreases in
      problems over time. CONCLUSIONS: Participation in a BMI reduced alcohol use and
      problems among mandated college students at 1-month follow-up. We identified
      predictors of these outcomes, which suggest the need to tailor the BMI to improve
      its efficacy among males and those students expressing motives (pro and cons, and
      fun seeking) and beliefs about the centrality of drinking in college.

PMID- 29032318
TI  - Adolescent substance use: Latent class and transition analysis.
AB  - BACKGROUND: The prevention and intervention of adolescent substance use is a
      public health priority. Most adolescents will engage in some form of substance
      use, and a sizeable minority will transition to using multiple substances. An
      emerging body of research takes a person-centered approach to model adolescent
      substance use over time; however, the findings have been equivocal. Our study
      modeled adolescent substance use transition patterns over three years based on a
      comprehensive list of substances and examined gender as a moderator. METHODS: We
      used three annual waves of data (Time 2, Time 3, and Time 4) from an ongoing
      longitudinal study of an ethnically diverse sample of 1042 adolescents originally
      recruited from multiple high schools in southeast Texas. Participants were 56%
      female, 32% Hispanics, 30% Whites, 29% African Americans, and 9% other with an
      average of 16.1years (SD=0.79) at Time 2. Data were analyzed using latent
      transition analyses. RESULTS: The study identified three substance use statuses
      (Mild Alcohol Use, Alcohol and Moderate Marijuana Use, and Polysubstance Use) and
      suggested that adolescents generally remained in the same statuses over time.
      When they did transition, it was typically to a more harmful substance use
      status. Further, males were more likely than females to be polysubstance users
      and had higher probabilities of transiting to and remaining in a more harmful
      drug use status. CONCLUSIONS: The study identifies overall and gender specific
      adolescent substance use transition patterns, which are vital to informing
      intervention development.

PMID- 29032320
TI  - Methodological issues of assessing the risk of a second cancer occurring in the
      same site as a first cancer using registry data.
AB  - OBJECTIVE: To present methodological issues that can arise with the assessment of
      the risk of a second primary cancer (SPC) occurring in the same site as a first
      cancer using registry data. MATERIAL AND METHODS: Data from ten French cancer
      registries were used, including data for patients with a first prostate cancer
      (in males), breast cancer (in females), and colon, lung and kidney cancer (in
      both sexes) diagnosed between 1989 and 2004. Standardized incidence ratios (SIRs)
      of SPC were computed by excluding, or not, the risk of an SPC at the same site.
      RESULTS: For prostate cancer, the SIR dropped from 1.11 to 0.72 when the risk of
      SPC of the prostate was included. SIRs increased from 1.36 to 1.45, from 1.14 to
      1.21, from 1.57 to 2.01, and from 1.37 to 1.51 for breast, colon, lung, and
      kidney respectively. CONCLUSION: The inclusion, or not, of an SPC at the same
      site can impact on SPC risk estimates.

PMID- 29032319
TI  - Peri-operative blood transfusion for resected colon cancer: Practice patterns and
      outcomes in a population-based study.
AB  - BACKGROUND & OBJECTIVES: Literature suggests that peri-operative blood
      transfusion among patients with resected colon cancer may be associated with
      inferior long-term survival. The study objective was to characterize this
      association in our population. METHODS: This is a retrospective cohort study
      using the population-based Ontario Cancer Registry (2002-2008). Pathology reports
      were obtained for a 25% random sample of all cases and constituted the study
      population. Log binomial regression was used to identify factors associated with
      transfusion. Cox proportional hazards model explored the association between
      transfusion and cancer specific survival (CSS) and overall survival (OS).
      RESULTS: The study population included 7198 patients: 18% stage I, 36% stage II,
      40% stage III, and 6% stage IV. Twenty-eight percent of patients were transfused.
      Factors independently associated with transfusion included advanced age
      (p<0.001), female sex (p<0.001), greater comorbidity (p<0.001), more advanced
      disease (p<0.001) and open surgical resection (p<0.001). Transfusion was
      associated with inferior CSS (HR 1.51, 95% CI 1.38-1.65) and OS (HR 1.52, 95% CI
      1.41-1.63), after adjusting for important confounders. CONCLUSIONS: Peri
      operative transfusion rates among patients with colon cancer have decreased over
      time. Transfusion is associated with inferior long-term CSS and OS.

PMID- 29032321
TI  - Acne in late adolescence is not associated with a raised risk of subsequent
      malignant melanoma among men.
AB  - BACKGROUND: To evaluate the association of acne in late adolescence with the risk
      for subsequent malignant melanoma (MM) in men. METHODS: Swedish register-based
      cohort study of 242,096 males born between 1952 and 1956, who took part in
      compulsory assessments for Swedish military conscription in late adolescence
      between 1969 and 1975, with subsequent diagnoses of MM (n=1,058) up to December
      31, 2009. Covariates included measures of childhood circumstances and information
      from adolescence on presence of acne, physical fitness, cognitive function, body
      mass index (BMI), and a summary of diagnoses. Cox regression was used for the
      analysis. RESULTS: In total 1,058 men were diagnosed with MM. Acne was not
      associated with subsequent MM, with an adjusted hazard ratio (and 95% confidence
      interval) of 0.95 (0.61 to 1.49). Men with parents who were agricultural workers,
      and men who lived in northern Sweden, had lower physical fitness, or lower
      cognitive function had a lower risk of MM. Overweight and obesity was associated
      with a raised risk, with an adjusted hazard ratio of 1.39 (1.14, 1.71).
      CONCLUSIONS: Acne in late adolescence is unlikely to represent a raised risk for
      subsequent MM in men. Overweight or obesity was identified as a raised risk for
      MM, possibly due to the associated increased skin surface area.

PMID- 29032322
TI  - Classroom social experiences in early elementary school relate to diurnal
      cortisol levels.
AB  - Social stress has been linked to altered hypothalamic-pituitary-adrenocorticol
      (HPA) axis activation. During elementary school, children can become exposed to
      negative peer relations, such as poor appraisal among classroom peers, which is
      considered a social stressor. However, little is known about the association
      between classroom peer appraisal and the physiological stress system in children.
      The goal of this study was to examine the association of peer acceptance and peer
      non-acceptance with diurnal cortisol concentrations in 222 children from 20
      mainstream elementary schools (Mage=6.97years, SD=0.99, 55% boys) in the
      Netherlands. Saliva samples were collected at awakening, 30min post-awakening, at
      noon and at 8 pm during a weekend day. From these assessments, the Cortisol
      Awakening Response (CAR), diurnal cortisol concentration (AUCg) and diurnal
      cortisol slope were calculated. Peer nominations of peer acceptance (being
      liked), and peer non-acceptance (being disliked) were collected across a one year
      interval. Associations were controlled for peer victimization, age, sex and SES
      and children's levels of emotional problems and behavioural problems. Results
      showed that low peer acceptance was associated with heightened diurnal cortisol
      concentration (i.e., heightened AUGg), lower cortisol reductions across the day
      (i.e., less decreasing cortisol slope) and heightened cortisol awakening response
      (i.e., heightened CAR). Peer non-acceptance and the interaction between peer
      acceptance and peer non-acceptance (known as peer rejection) were not associated
      with AUCg, cortisol slope or the CAR. The findings emphasize the association
      between poor appraisal among classroom peers and children's heightened HPA-axis
      activation. This underscores the importance of the physiological stress system in
      studying the consequences of negative peer relations in children.

PMID- 29032324
TI  - Intranasal oxytocin, social cognition and neurodevelopmental disorders: A meta
      analysis.
AB  - Deficits in social cognition are pervasive and characteristic of
      neurodevelopmental disorders (NDDs). Clinical trials of intranasal oxytocin (IN
      OT) to improve social cognition have yielded inconclusive results. The current
      study is a meta-analysis of randomized controlled trials (RCTs) considering the
      effect of IN-OT on social cognitive domains across a range of NDDs. Medline,
      PsychINFO and Scopus were searched for RCTs published through to July 25, 2017.
      Seventeen studies met inclusion criteria, comprising 466 participants with a NDD.
      Meta-analysis using a random-effects model, revealed that IN-OT had no
      significant effect on emotion recognition (Hedges' g=0.08), a moderate but non
      significant effect on empathy (Hedges' g=0.49), and a small, significant effect
      on theory of mind (ToM) (Hedges' g=0.21). Meta-regression indicated that the
      effect of IN-OT on social cognition was not moderated by the diagnosis or age of
      participants, or the dose or frequency of IN-OT administration. The results
      highlight a need for more well-designed RCTs, as it remains difficult to draw
      conclusions about the potential for IN-OT to improve social cognition in NDDs.
      The promise of IN-OT should be considered tentative.

PMID- 29032323
TI  - Neural activity during traumatic film viewing is linked to endogenous estradiol
      and hormonal contraception.
AB  - Women are at higher risk for Posttraumatic Stress Disorder (PTSD) and recent
      research has highlighted a modulating role of female sex hormones for cognitive
      and emotional processes potentially underlying PTSD symptoms. However, studies
      combining fMRI recordings of brain activity during trauma film viewing with
      assessment of female sex hormones are missing. The trauma film paradigm - a
      widely used experimental analogue for trauma exposure - confronts healthy
      participants with traumatic film clips and thus allows studying peritraumatic
      processing under laboratory conditions. Following this paradigm, the current fMRI
      study examined the role of endogenous estradiol and synthetic sex hormones for
      the neural processing of traumatic (i.e., depicting interpersonal violence) vs.
      neutral films in 53 healthy women (mean age 22.3 years; 23 using hormonal
      contraception, HC). As predicted, traumatic films strongly activated areas of the
      fear processing network, such as amygdala, insula, and dorsal anterior cingulate
      cortex. Estradiol levels in women not using HC were positively correlated with
      ventromedial prefrontal activity. Furthermore, women using HC as compared to
      women without HC demonstrated heightened insula and dorsal anterior cingulate
      cortex activity during traumatic film viewing. These experimental results
      highlight the effects of both gonadal hormone status and HC intake on
      peritraumatic processing in neural regions relevant for emotion generation and
      regulation that have been found to be abnormal in PTSD.

PMID- 29032326
TI  - Production of hybrid macro/micro/nano surface structures on Ti6Al4V surfaces by
      picosecond laser surface texturing and their antifouling characteristics.
AB  - The development of surfaces which reduce biofouling has attracted much interest
      in practical applications. Three picosecond laser generated surface topographies
      (Ti1, Ti2, Ti3) on titanium were produced, treated with fluoroalkylsilane (FAS),
      then characterised using Scanning Electron Microscopy (SEM), Energy Dispersive X
      ray Spectroscopy (EDX), Raman Spectroscopy, Fourier Transform Infra-Red (FTIR)
      spectroscopy, contact angle measurements and white light interference microscopy.
      The surfaces had a range of different macro/micro/nano topographies. Ti2 had a
      unique, surface topography with large blunt conical peaks and was predominantly a
      rutile surface with closely packed, self-assembled FAS; this was the most
      hydrophobic sample (water contact angle 160 degrees ; DeltaGiwi was -135.29mJm
      2). Bacterial attachment, adhesion and retention to the surfaces demonstrated
      that all the laser generated surfaces retained less bacteria than the control
      surface. This also occurred following the adhesion and retention assays when the
      bacteria were either not rinsed from the surfaces or were retained in static
      conditions for one hour. This work demonstrated that picosecond laser generated
      surfaces may be used to produce antiadhesive surfaces that significantly reduced
      surface fouling. It was determined that a tri-modally dimensioned surface
      roughness, with a blunt conical macro-topography, combined with a close-packed
      fluoroalkyl monolayer was required for an optimised superhydrophobic surface.
      These surfaces were effective even following surface immersion and static
      conditions for one hour, and thus may have applications in a number of food or
      medical industries.

PMID- 29032325
TI  - Novel quinoline incorporating 1,2,4-triazole/oxime hybrids: Synthesis, molecular
      docking, anti-inflammatory, COX inhibition, ulceroginicity and histopathological
      investigations.
AB  - A series of novel quinolines incorporating 1,2,4-triazole/oxime hybrids were
      prepared. They showed remarkable anti-inflammatory activity and exhibited very
      low incidence of gastric ulceration, compared to indomethacin. Most of the
      compounds tested showed remarkable inhibition of the COX-1 isozyme, with IC50's
      ranging from 0.48 to 28uM. Compounds 7c and 9g showed high safety profiles with
      normal stomach tissue integrity. Docking studies supported the observed in vitro
      inhibitory activity towards the COX enzymes that may explain their promising anti
      inflammatory activity relative to indomethacin. Moreover, differences between the
      COX-1 and COX-2 isozymes in observed energy scores, as well as in the number of
      interactions with some of the compounds tested, might predict their higher
      selectivity towards COX-1 rather than COX-2. Compound 9e was found to inhibit
      both COXs non-competitively with Ki values of 81uM and 94.6uM.

PMID- 29032327
TI  - A general dead-time correction method based on live-time stamping. Application to
      the measurement of short-lived radionuclides.
AB  - Dead-time correction formulae are established in the general case of superimposed
      non-homogeneous Poisson processes. Based on the same principles as conventional
      live-timed counting, this method exploits the additional information made
      available using digital signal processing systems, and especially the possibility
      to store the time stamps of live-time intervals. No approximation needs to be
      made to obtain those formulae. Estimates of the variances of corrected rates are
      also presented. This method is applied to the activity measurement of short-lived
      radionuclides.

PMID- 29032328
TI  - Effect of the anode potential on the physiology and proteome of Shewanella
      oneidensis MR-1.
AB  - Shewanella species respire using iron and manganese oxides as well as electrodes
      as solid terminal electron acceptors. Shewanella oneidenis MR-1 exploits mediated
      as well as direct extracellular electron transfer (EET) modes to transfer
      electrons at different formal potentials. These different EET modes at different
      potentials may utilise alternate electron transfer pathways. Therefore, we
      investigated how different anode potentials, providing different maximum
      microbial energy gains impacted S. oneidensis microbial physiology. Using
      quantitative proteomics, comparative analysis of the cellular variations to
      different anode potentials was performed. A label-free proteomic mass
      spectrometric analysis method, SWATH-MS, was used to gather quantitative
      information to determine physiological changes of Shewanella oneidensis MR-1
      grown at different anodic potentials. S. oneidensis was cultured and grown in
      electrochemical cells at the set anode potentials of +0.71V, +0.21V & -0.19V
      versus SHE reference electrode, while the current production was monitored. At
      maximum current, electrodes were removed and whole-cell proteins extracted.
      Subsequent SWATH-MS analysis revealed information on 740 identified proteins
      across the three electrode potentials. For the first time, we show the abundance
      of S. oneidensis electron transfer proteins differs with electrode potential.

PMID- 29032329
TI  - Successful transdermal allergen delivery and allergen-specific immunotherapy
      using biodegradable microneedle patches.
AB  - Allergen-specific immunotherapy (SIT) is an effective treatment modality for
      allergic diseases such as atopic dermatitis (AD). However, frequent visits over a
      3-year period as well as looming adverse events tend to discourage patient
      compliance. Therefore, a more convenient, effective, and safe method of SIT is
      needed. For several decades, use of microneedles has been promoted as an
      efficient and precise transdermal drug delivery method. In this study, we
      developed Dermatophagoides farinae (D. farinae) extract (DfE)-loaded microneedle
      patches, and evaluated their safety and efficacy as a novel SIT method. After 4
      weeks of patch application, efficient allergen delivery and successful induction
      of immune response to DfE were demonstrated in mice, with no apparent adverse
      events. AD-induced NC/Nga mice received microneedle immunotherapy (MNIT) (10
      MUg), subcutaneous immunotherapy (SCIT) (10 MUg), SCIT (100 MUg), or placebo.
      Both MNIT (10 MUg) and SCIT (100 MUg) treatments improved clinical and histologic
      manifestations of AD skin lesions, altered immunoglobulin production, dampened
      Th2 cellular response, and boosted Treg infiltrates, without significant side
      effects; whereas SCIT (10 MUg) or placebo subsets failed to show any effects.
      Based on the favorable safety and efficacy profiles demonstrated in mice by MNIT
      in the current study, we believe that MNIT may serve as a new SIT modality.

PMID- 29032330
TI  - Biofabricating atherosclerotic plaques: In vitro engineering of a three
      dimensional human fibroatheroma model.
AB  - Atherosclerotic plaques are cholesterol-induced inflammatory niches accumulating
      in the vascular sub-endothelial space. Cellular and extracellular composition of
      human plaques is maneuvered by local inflammation that leads to alterations in
      the original vascular microenvironment and to the recruitment of an invading
      fibrous layer (fibroatharoma). In the present study we introduce a bioengineered
      three-dimensional model of human fibroatheroma (ps-plaque) assembled with a
      tailored hanging-drop protocol. Using vi-SNE based multidimensional flow
      cytometry data analysis we compared the myeloid cell-populations in ps-plaques to
      those in plaques isolated from human carotid arteries. We observed that
      plasmacytoid and activated dendritic cells are the main myeloid components of
      human carotid plaques and that both cell types are present in the biofabricated
      model. We found that low-density lipoproteins affect cell viability and
      contribute to population polarization in ps-plaques. The current work describes
      the first human bioengineered in vitro model of late atherosclerotic lesion for
      the investigation of atherosclerosis aetiopathogenesis.

PMID- 29032331
TI  - Unraveling the mechanistic effects of electric field stimulation towards
      directing stem cell fate and function: A tissue engineering perspective.
AB  - Electric field (EF) stimulation can play a vital role in eliciting appropriate
      stem cell response. Such an approach is recently being established to guide stem
      cell differentiation through osteogenesis/neurogenesis/cardiomyogenesis. Despite
      significant recent efforts, the biophysical mechanisms by which stem cells sense,
      interpret and transform electrical cues into biochemical and biological signals
      still remain unclear. The present review critically analyses the variety of EF
      stimulation approaches that can be employed to evoke appropriate stem cell
      response and also makes an attempt to summarize the underlying concepts of this
      notion, placing special emphasis on stem cell based tissue engineering and
      regenerative medicine. This review also discusses the major signaling pathways
      and cellular responses that are elicited by electric stimulation, including the
      participation of reactive oxygen species and heat shock proteins, modulation of
      intracellular calcium ion concentration, ATP production and numerous other events
      involving the clustering or reassembling of cell surface receptors, cytoskeletal
      remodeling and so on. The specific advantages of using external electric
      stimulation in different modalities to regulate stem cell fate processes are
      highlighted with explicit examples, in vitro and in vivo.

PMID- 29032332
TI  - Long-term treatment with chaethomellic acid A reduces glomerulosclerosis and
      arteriolosclerosis in a rat model of chronic kidney disease.
AB  - The high prevalence of end-stage renal disease emphasizes the failure to provide
      therapies to effectively prevent and/or reverse renal fibrosis. Therefore, the
      aim of this study was to evaluate the effect of long-term treatment with
      chaethomellic acid A (CAA), which selectively blocks Ha-Ras farnesylation, on
      renal mass reduction-induced renal fibrosis. Male Wistar rats were sham-operated
      (SO) or subjected to 5/6 renal mass reduction (RMR). One week after surgery, rats
      were placed in four experimental groups: SO:SO rats without treatment (n=13);
      SO+CAA: SO rats treated with CAA (n=13); RMR:RMR rats without treatment (n=14);
      and RMR+CAA:RMR rats treated with CAA (n=13). CAA was intraperitoneally
      administered in a dose of 0.23MUg/kg three times a week for six months. Renal
      fibrosis was evaluated by two-dimensional ultrasonography and histopathological
      analysis. The kidneys of the RMR animals treated with CAA showed a significantly
      decrease in the medullary echogenicity (p<0.05) compared with the RMR rats that
      received no treatment. Glomerulosclerosis and arteriolosclerosis scores were
      significantly lower (p<0.001) in the RMR+CAA group when compared with the RMR
      group. There were no significant differences in interstitial fibrosis,
      interstitial inflammation and tubular dilatation scores between the RMR+CAA and
      RMR groups. These data suggest that CAA can be a potential future drug to
      attenuate the progression of chronic kidney disease.

PMID- 29032333
TI  - Glucagon-like peptide-1 improves beta-cell dysfunction by suppressing the miR-27a
      induced downregulation of ATP-binding cassette transporter A1.
AB  - Lipotoxicity is considered one of the main causes of deterioration in beta-cells
      function. Glucagon-like peptide-1 (GLP-1) has been revealed to protect and
      improve pancreatic beta-cell function against lipotoxicity. However, the
      mechanism behind these is largely unknown. The aim of this study was to
      investigate the effects of GLP-1 on cholesterol-induced lipotoxicity in INS-1
      cells and examine the underlying mechanisms. The cell viability was determined,
      and caspase-3 was used to assess the effects of GLP-1 on cholesterol-induced
      apoptosis. The alterations of miR-27a and ABCA1 resulting from incubation with
      cholesterol or GLP-1 were detected by real-time PCR and western blot. The
      inhibition and overexpression of miR-27a were established to explore the effects
      of a GLP-1-mediated decrease in miR-27a. Further, Oil red O staining and
      cholesterol measurement were used to detect lipid accumulation. The beta-cells
      function was measured in glucose-stimulated insulin secretion. Our data shows
      that cholesterol significantly attenuated cell viability, promoted cell
      apoptosis, facilitated lipid accumulation, and impaired beta-cells function, and
      these effects were significantly reversed by GLP-1. Furthermore, the results
      demonstrated that GLP-1 decreased miR-27a expression and increased the expression
      of ABCA1. In conclusion, GLP-1 may affect cholesterol accumulation and beta-cells
      dysfunction by regulating the expression of miR-27a and ABCA1.

PMID- 29032334
TI  - Anti-hypersensitivity effects of the phthalimide derivative N-(4methyl-phenyl)-4
      methylphthalimide in different pain models in mice.
AB  - The treatment of chronic pain remains a challenge for clinicians worldwide,
      independent of its pathogenesis. It motivates several studies attempting to
      discover strategies to treat the disease. The in silico analysis using molecular
      docking approach demonstrated that the phthalimide N-(4methyl-phenyl)-4
      methylphthalimide (MPMPH-1) presented high affinity to adenylyl-cyclase enzyme
      (AC). It also prominently reduced the mechanical hypersensitivity of mice
      challenged by Forskolin, an AC activator. This effect lasted for up to 48h after
      Forskolin injection, presenting activity longer than MDL-12330A (AC inhibitor).
      MPMPH-1 was also effective in reducing the hypersensitivity induced by IL-1beta,
      bradykinin, prostaglandin E2 or epinephrine, chemical mediators that have, among
      others, AC as pivotal protein in their signalling cascade to induce mechanical
      pain behaviour. The compound presented marked inhibition in inflammatory-pain
      models induced by carrageenan, lipopolysaccharide or complete Freund's adjuvant,
      including neutrophil migration inhibition. Furthermore, it also seems to act in
      both peripheral and pain central-control pathways, being also effective in
      reducing the persistent cancer-pain behaviour induced by melanoma cells in mice.
      MPMPH-1 could represent a promising pharmacological tool to treat acute and
      chronic painful diseases, with good bioavailability, local activity, and lack of
      locomotor-activity interference. Further studies are necessary to determine the
      exact mechanism of action but it seems to involve AC enzyme as possible target.

PMID- 29032335
TI  - Identification of the optimal dose and calpain system regulation of
      tetramethylpyrazine on the prevention of skeletal muscle atrophy in hindlimb
      unloading rats.
AB  - Previous studies in our lab have shown that tetramethylpyrazine (TMP) could
      effectively attenuate disuse induced muscle atrophy. In order to screening out
      the optimal dose of tetramethylpyrazine (TMP) for protection against disuse
      induced muscle atrophy in hindlimb unloading (HLU) rats, in this study, we
      compared effects of 4 TMP doses on muscle wet weight (MWW), the ratios of muscle
      wet weight/body weight (MWW/BW) and muscle wet weight/dry weight (MWW/DW), fiber
      type composition, as well as cross-sectional area (CSA) in soleus (SOL) muscle.
      Consequently, we quantified optimal dose effects on both functional properties
      and protein expression (calpain-1, calpain-2, calpastatin and MuRF1) in SOL and
      extensor digitorum longus (EDL) muscles. Data indicated that the protective
      potential of TMP was dose-dependent: 60mg/kg TMP was most effective in terms of
      atrophy prevention. This dose reduced SOL MWW, MWW/BW and CSA muscle loss by 60,
      60 and 54% (P<0.001), respectively. HLU-induced slow-to-fast fiber transition was
      reduced by 17% (P<0.01). 60mg/kg TMP also significantly lessened the decrease of
      contractile force, the increase of shorting velocity and fatigability induced by
      HLU. Besides, it also attenuated expressions of calpain-1 (SOL -8.6%, P<0.05; EDL
      -10.9%, P<0.05), calpain-2 (SOL -60%, P<0.001; EDL -32%, P<0.01) and MuRF1
      expression (SOL -21%, P<0.001; EDL -10%, P<0.01), promoted the expression of
      calpastatin by 18% (P<0.05) in SOL muscle. Taken together, present study
      demonstrated that 60mg/kg body weight was the optimal dose of TMP against disuse
      induced muscle atrophy which effectively protected muscle function by inhibiting
      calpain-1, calpain-2 and MuRF1 expression, promoted calpastatin expression,
      especially in slow-twitch muscle.

PMID- 29032336
TI  - A mouse dry eye model induced by topical administration of the air pollutant
      particulate matter 10.
AB  - AIM: To introduce a novel dry eye mouse model induced by topical administration
      of the air pollutant particulate matter 10 (PM10). METHOD: A total of 60 male
      BALB/c mice were used in this study and divided into two groups: group A (PBS eye
      drops, n=30) and group B (PM10 eye drop group, n=30). Each treatment was dosed
      four times a day, every time 50ul with the concentration of 5mg/ml PM10, for 14
      consecutive days in the right eye. The clinical manifestations of dry eye were
      measured before therapy and 4, 7 and 14days post-treatment respectively, which
      included the tear volume, tear break-up (BUT) time, corneal fluorescein staining,
      rose bengal staining, Lissamine Green staining and inflammatory index. Eye
      samples were collected on D14 and examined by histologic light microscopy,
      transmission electron microscopy (TEM) and scanning electron microscopy (SEM),
      corneal cytokeration 10 (K10) immunnostaining, and tumor necrosis factor-alpha
      (TNF-alpha), NF-kappaB-p65 and NF-kappaB Western Blot analysis. RESULTS: At 0d,
      7d and 14d, there were no statistical changes in tear volume, BUT after treatment
      (P>0.05) with PBS in group A. In group B, all items showed statistical
      differences at each time point (P<0.05). At 14d after therapy, the fluorescein
      staining score of group B was higher than group A (P<0.05). The score of rose
      bengal staining and Lissamine Green staining in group B was also higher than that
      in group A (P<0.05). The number of mean layers of corneal epithelial cells in the
      group A was significantly lower than that in the group B (P<0.05). TEM and SEM
      revealed that the number of corneal epithelial microvilli were drastically
      reduced in group B. The number of corneal chondriosome/desmosomes was also
      reduced in group B by TEM. PM10 induced apoptosis in the superficial and basal
      corneal epithelium, and leaded to abnormal differentiation and proliferation of
      the ocular surface with higher expression levels of K10 and reduced number of
      goblet cells in the conjunctival fornix in group B. PM10 significantly increased
      the levels of TNF-alpha, NF-kappaB-p65 and NF-kappaB in the cornea. CONCLUSION:
      PM10 can damage the tear film function and cause the destruction of the
      structural organization of ocular surface in mice. Topical administration of PM10
      in mice induces ocular surface changes that are similar to those of dry eye in
      humans, representing a novel model of DES.

PMID- 29032337
TI  - MiR-758-3p suppresses proliferation, migration and invasion of hepatocellular
      carcinoma cells via targeting MDM2 and mTOR.
AB  - Hepatocelluar carcinoma (HCC) is one of the most frequently diagnosed cancers
      worldwide and among the leading causes of cancer-related death. Although
      deregulation of microRNAs has been frequently described in HCC, imperfection is
      known about the precise molecular mechanisms by which microRNAs modulate the
      process of tumorogenesis and behavior of cancer cells. In this study, we
      demonstrated that miR-758-3p could suppress cell proliferation, migration and
      invasion in hepatocellular carcinoma cells. We screened and identified two novel
      miR-758-3p targets, MDM2 and mTOR. Up-regulation of miR-758-3p could specifically
      and markedly down-regulate the expression of MDM2 and mTOR. Additionally, miR-758
      3p over-expression displayed significant suppression in HCC development. To
      identify the mechanisms, we further investigated the P53 and mTOR pathway and
      found that p-p70S6 kinase(Ser371), p-p70 S6 kinase(Thr389) and p-4E-BP1were
      dramatically down-regulated after miR-758-3p transfection, while an enhanced
      expression of P53, AKT and PRAS40 were visualized, thus suggesting that the role
      of miR-758-3p in HCC progression may be associated with MDM2-p53 and mTOR
      signaling pathways. Collectively, our results indicate that miR-758-3pserves as a
      tumor suppressor and plays a crucial role in inhibiting the proliferation,
      migration and invasion of HCC via targeting MDM2 and mTOR and implicate its
      potential application in cancer therapy.

PMID- 29032338
TI  - An analysis of suppressing migratory effect on human urinary bladder cancer cell
      line by silencing of snail-1.
AB  - BACKGROUND: Snail-1 actively participates in tumor progression, invasion, and
      migration. Targeting snail-1 expression can suppress the EMT process in cancer.
      The aim of this study was to investigate the effect of snail1 silencing on
      urinary bladder cancer. METHODS: Quantitative RT-PCR was used to detect snail-1
      and other related metastatic genes expression following siRNA knockdown in
      urinary bladder cancer EJ-138 cells. The protein level of snail1 was assessed by
      Western blot. MTT and TUNEL assays were assessed to understand if snail-1 had
      survival effects on EJ-138 cells. Scratch wound healing assay measured cell
      motility effects after snail1 suppression. RESULTS: The significant silencing of
      snail-1 reached 60pmol siRNA in a 48-h post-transfection. The result of scratch
      assay showed that snail-1 silencing significantly decreased Vimentin, MMPs, and
      CXCR4 expression; however, expression of E-cadherin was induced. The cell death
      assay indicated that snail-1 played the crucial role in bladder cancer survival
      rate. CONCLUSION: These results propose that snail-1 plays a major role in the
      progression and migration of urinary bladder cancer, and can be a potential
      therapeutic target for target therapy of invasive urinary bladder cancer.

PMID- 29032339
TI  - Synthesis and evaluation of anticancer activity of BOC26P, an ortho-aryl chalcone
      sodium phosphate as water-soluble prodrugs in vitro and in vivo.
AB  - Major limitations of chalcones as clinical anticancer agents are water
      insolubility and poor bioavailability, which may be improved by a classic
      phosphate prodrug strategy that targets non-specific alkaline phosphatase (ALP)
      for releasing the parent drug in vivo. In this study, we found that BOC26P, a
      phosphate prodrug of chalcone OC26, exhibits excellent water solubility and
      improved plasma concentration in vivo by either i.v. or p.o. compared with the
      parent drug. In pace with decreased inhibitory activity of BOC26P against
      microtubule polymerization in vitro and in cells, the antiproliferative activity
      of BOC26P is attenuated in A549 and HLF cells. However, the antitumor effect of
      BOC26P increases in an A549 xenograft model as compared to the equimolar
      concentration of OC26, suggesting that complex tumor microenvironment would be
      another important influence factor to regulate the antitumor activity of BOC26Pin
      vivo. In conclusion, these observations showed that the traditional phosphate
      prodrug strategy would be a promising and easy method to increase water
      solubility and anticancer activity of chalcones for the clinical developments of
      anticancer agents.

PMID- 29032340
TI  - Quinic acid inhibits vascular inflammation in TNF-alpha-stimulated vascular
      smooth muscle cells.
AB  - Atherosclerosis is a chronic inflammatory disease, and the increased expression
      of adhesion molecules on vascular smooth muscle cells contributes to the
      progression of vascular disease. Quinic acid (QA) has been shown to possess
      radioprotection, anti-neuroinflammatory, and anti-oxidant activities; however, an
      anti-vascular inflammatory effect has not been reported. This study investigated
      the effect of QA on the expression of vascular cell adhesion molecule-1 (VCAM-1)
      stimulated by TNF-alpha in MOVAS cells. Pre-incubation of MOVAS cells, the mouse
      vascular smooth muscle cell line for 2h with QA (0.1, 1 and 10 MUg/mL) dose
      dependently inhibits TNF-alpha-induced mRNA and protein expression of VCAM-1 and
      monocyte adhesion. QA inhibits TNF-alpha-stimulated phosphorylation of MAP kinase
      and NK-kappaB activation. Our results indicate that QA inhibits the TNF-alpha
      stimulated induction of VCAM-1 in VSMC by inhibiting the MAP kinase and NF-kappaB
      signaling pathways and the adhesion capacity of VSMC, which may explain the
      ability of QA to inhibit vascular inflammation such as atherosclerosis.

PMID- 29032341
TI  - Ethyl acetate fraction of Eclipta alba: a potential phytopharmaceutical targeting
      adipocyte differentiation.
AB  - Natural products have always fascinated mankind for their miraculous properties.
      Eclipta alba (E. alba), a medicinal herb has long been used in traditional
      medicine for curing several pathologies. It has been shown to have anti-diabetic
      effect as well as hepato-protective activity. Here, in order to address metabolic
      derangements, the study was designed to evaluate the efficacy of E. alba and its
      fractions in adipogenesis inhibition and dyslipidemia. Of the crude extract and
      fractions screened, ethyl acetate fraction of E. alba inhibited adipocyte
      differentiation in 3T3-L1 pre-adipocytes and hMSC derived adipocytes. It
      inhibited mitotic clonal expansion and caused cell cycle arrest in G1 and S phase
      as suggested by western blot analysis and flow cytometry. It was also shown to
      have lipolytic effects. Oral administration of ethyl acetate fraction of E. alba
      to hamsters unveiled its anti-adipogenic as well as anti-dyslipidemic activity in
      vivo. Mass spectrometry analysis of ethyl acetate fraction confirmed the presence
      of several bioactive components, projecting it as an effective
      phytopharmaceutical agent. In conclusion, ethyl acetate fraction of E. alba
      possesses potent anti-adipogenic as well as anti-dyslipidemic activity and could
      be projected as an herbal formulation towards obesity.

PMID- 29032342
TI  - A light-up probe targeting for Bcl-2 2345 G-quadruplex DNA with carbazole TO.
AB  - As its significant role, the selective recognition of G-quadruplex with specific
      structures and functions is important in biological and medicinal chemistry.
      Carbazole derivatives have been reported as a kind of fluorescent probe with many
      excellent optical properties. In the present study, the fluorescence of the dye
      (carbazole TO) increased almost 70 fold in the presence of bcl-2 2345 G4 compared
      to that alone in aqueous buffer condition with almost no fluorescence and 10-30
      fold than those in the presence of other DNAs. The binding study results by
      activity inhibition of G4/Hemin peroxidase experiment, NMR titration and
      molecular docking simulation showed the high affinity and selectivity to bcl-2
      2345 G4 arises from its end-stacking interaction with G-quartet. It is said that
      a facile approach with excellent sensitive, good selectivity and quick response
      for bcl-2 2345 G-quadruplex was developed and may be used for antitumor
      recognition or antitumor agents.

PMID- 29032343
TI  - Highly selective and sensitive colorimetric determination of Cr3+ ion by 4-amino
      5-methyl-4H-1,2,4-triazole-3-thiol functionalized Au nanoparticles.
AB  - In this work, a rapid, selective naked eyes colorimetric chemical probe for the
      detection of Cr3+ was developed based on functionalization of gold nanoparticles.
      For this purpose, surface of Au NPs was functionalized using 4-amino-5-methyl-4H
      1,2,4-triazole-3-thiol (AMTT). Through colorimetric studies, it was found that in
      the presence of Cr3+ ions, AMTT-Au NPs instantly aggregated and resulted in a
      color change of the solution from red to blue. The color change of AMTT-Au NPs
      due to the aggregation induced by Cr3+ can be seen with even naked eyes and also
      by UV-Vis spectroscopy with a detection limit of 1.8MUM and 0.1MUM, respectively.
      AMTT-Au NPs showed excellent selectivity toward Cr3+ compared to other cations
      tested, including K+, Na+, Cs+, Fe3+, Ni2+, Cu2+, Co2+, Zn2+, Ba2+, Ca2+, Mg2+,
      Cd2+, Pb2+, Hg2+ ions and especially all trivalent lanthanide ions. The
      absorbance ratio (A650/A525) was linear toward Cr3+ concentrations in the range
      of 0.6-6.1MUM (R2=0.996). The best response was achieved over a pH range of 3-5.
      Furthermore, the proposed colorimetric method based on AMTT-Au NPs was
      successfully used for Cr3+ ion detection in plasma sample and some water samples.

PMID- 29032344
TI  - Simultaneous determination of alpha-asarone and beta-asarone in Acorus
      tatarinowii using excitation-emission matrix fluorescence coupled with
      chemometrics methods.
AB  - A chemometrics-assisted excitation-emission matrix (EEM) fluorescence method was
      proposed for simultaneous determination of alpha-asarone and beta-asarone in
      Acorus tatarinowii. Using the strategy of combining EEM data with chemometrics
      methods, the simultaneous determination of alpha-asarone and beta-asarone in the
      complex Traditional Chinese medicine system was achieved successfully, even in
      the presence of unexpected interferents. The physical or chemical separation step
      was avoided due to the use of "mathematical separation". Six second-order
      calibration methods were used including parallel factor analysis (PARAFAC),
      alternating trilinear decomposition (ATLD), alternating penalty trilinear
      decomposition (APTLD), self-weighted alternating trilinear decomposition
      (SWATLD), the unfolded partial least-squares (U-PLS) and multidimensional partial
      least-squares (N-PLS) with residual bilinearization (RBL). In addition, HPLC
      method was developed to further validate the presented strategy. Consequently,
      for the validation samples, the analytical results obtained by six second-order
      calibration methods were almost accurate. But for the Acorus tatarinowii samples,
      the results indicated a slightly better predictive ability of N-PLS/RBL procedure
      over other methods.

PMID- 29032345
TI  - Characterization of titanyl phthalocyanine (TiOPc) thin films by microscopic and
      spectroscopic method.
AB  - The titanyl phthalocyanine (TiOPc) thin film deposited on glass, silicon and gold
      substrate have been studied using Raman spectroscopy, atomic force microscopy
      (AFM), absorption and profilometry measurements. The TiOPc thin layers have been
      deposited at room temperature by the quasi-molecular beam evaporation technique.
      The Raman spectra have been recorded using micro Raman system equipped with a
      confocal microscope. Using surface Raman mapping techni que with polarized Raman
      spectra the polymorphic forms of the TiOPc thin films distribution have been
      obtained. The AFM height and phase image were examined in order to find surface
      features and morphology of the thin films. Additionally to compare experimental
      results, structure optimization and vibrational spectra calculation of single
      TiOPc molecule were performed using DFT calculations. The received results showed
      that the parameters like polymorphic form, grain size, roughness of the surface
      in TiOPc thin films can well characterize the obtained organic thin films
      structures in terms of their use in optoelectronics and photovoltaics devices.

PMID- 29032346
TI  - Fusion of Anthopleurin-B to AAV2 increases specificity of cardiac gene transfer.
AB  - AAV-mediated gene therapy has become a promising therapeutic strategy for chronic
      diseases. Its clinical utilization, however, is limited by the potential risk of
      off-target effects. In this work we attempt to overcome this challenge,
      hypothesizing that cardiac ion channel-specific ligands could be fused onto the
      AAV capsid, and narrow its tropism to cardiac myocytes. We successfully fused the
      cardiac sodium channel (Nav1.5)-binding toxin Anthopleurin-B onto the AAV2 capsid
      without compromising virus integrity, and demonstrated increased specificity of
      cardiomyocyte attachment. Although virus attachment to Nav1.5 did not supersede
      the natural heparan-mediated virus binding, heparan-binding ablated vectors
      carrying Anthopleurin-B eliminated hepatic and other extracardiac gene transfer,
      while preserving cardiac myocyte gene transfer. Virus binding to the cardiac
      sodium channel transiently decreased sodium current density, but did not cause
      any arrhythmias. Our findings expand the knowledge of attachment, infectivity,
      and intracellular processing of AAV vectors, and present an alternative strategy
      for vector retargeting.

PMID- 29032347
TI  - Vocalic transitions as markers of speech acoustic changes with STN-DBS in
      Parkinson's Disease.
AB  - PURPOSE: Deep Brain Stimulation of the subthalamic nucleus (STN-DBS) effectively
      treats cardinal symptoms of idiopathic Parkinson's disease (PD) that cannot be
      satisfactorily managed with medication. Research is equivocal regarding speech
      changes associated with STN-DBS. This study investigated the impact of STN-DBS on
      vocalic transitions and the relationship to intelligibility. METHODS: Eight
      Quebec-French speakers with PD and eight healthy controls participated. The slope
      of the second formant frequency (F2 slope) for glides was obtained. Locus
      equations (LEs) were calculated to capture vocalic transitions in consonant-vowel
      sequences. A visual analog scale was used to obtain judgments of intelligibility.
      Measures for the PD group were obtained both On and Off stimulation. RESULTS: F2
      slopes and LEs differed among groups, but there were no systematic differences
      for On versus Off STN-DBS. On an individual level, participants with PD exhibited
      heterogeneous changes with DBS stimulation. Intelligibility was significantly
      correlated with F2 slope. CONCLUSION: F2 slope appears to be sensitive to
      articulatory impairment in PD and could be used in clinical settings to
      distinguish these speakers from healthy controls. However, acoustic metrics
      failed to identify systematic change with STN-DBS. The heterogeneity of results,
      as well as the clinical relevance of acoustic metrics are discussed.

PMID- 29032349
TI  - Organizational home care models across Europe: A cross sectional study.
AB  - BACKGROUND: Decision makers are searching for models to redesign home care and to
      organize health care in a more sustainable way. OBJECTIVES: The aim of this study
      is to identify and characterize home care models within and across European
      countries by means of structural characteristics and care processes at the policy
      and the organization level. DATA SOURCES: At the policy level, variables that
      reflected variation in health care policy were included based on a literature
      review on the home care policy for older persons in six European countries:
      Belgium, Finland, Germany, Iceland, Italy, and the Netherlands. At the
      organizational level, data on the structural characteristics and the care
      processes were collected from 36 home care organizations by means of a survey.
      Data were collected between 2013 and 2015 during the IBenC project. STUDY DESIGN:
      An observational, cross sectional, quantitative design was used. The analyses
      consisted of a principal component analysis followed by a hierarchical cluster
      analysis. RESULTS: Fifteen variables at the organizational level, spread across
      three components, explained 75.4% of the total variance. The three components
      made it possible to distribute home care organizations into six care models that
      differ on the level of patient-centered care delivery, the availability of
      specialized care professionals, and the level of monitoring care performance.
      Policy level variables did not contribute to distinguishing between home care
      models. CONCLUSIONS: Six home care models were identified and characterized.
      These models can be used to describe best practices.

PMID- 29032348
TI  - Systems proteomics approaches to study bacterial pathogens: application to
      Mycobacterium tuberculosis.
AB  - Significant developments and improvements in basic and clinical research
      notwithstanding, infectious diseases still claim at least 13 million lives
      annually. Classical research approaches have deciphered many molecular mechanisms
      underlying infection. Today it is increasingly recognized that multiple molecular
      mechanisms cooperate to constitute a complex system that is used by a given
      pathogen to interfere with the biochemical processes of the host. Therefore,
      systems-level approaches now complement the standard molecular biology techniques
      to investigate pathogens and their interactions with the human host. Here we
      review omic studies in Mycobacterium tuberculosis, the causative agent of
      tuberculosis, with a particular focus on proteomic methods and their application
      to the bacilli. Likewise, the discussed methods are directly portable to other
      bacterial pathogens.

PMID- 29032350
TI  - Identifying characteristics of the most severely impaired chronic pain patients
      treated at a specialized inpatient pain clinic.
AB  - BACKGROUND AND AIMS: Patients suffering from chronic nonmalignant pain constitute
      a heterogeneous population in terms of clinical presentation and treatment
      results. Few data are available about what distinguishes different groups in this
      huge population of patients with chronic persistent pain (CPP). A subgroup that
      is poorly studied, consists of the most severely impaired chronic pain patients.
      At the Uppsala University Hospital Pain Clinic, there is a specialized department
      accepting the most complex patients for rehabilitation. In the endeavour to
      improve and evaluate treatment for this subgroup, a better understanding of the
      complex nature of the illness is essential. This prospective study aimed to
      describe the characteristics of this subgroup of patients with CPP. METHODS:
      Seventy-two consecutive patients enrolled in the Uppsala programme were
      evaluated. We collected data on demographics, type of pain and experienced
      symptoms other than pain using a checklist of 41 possible symptoms. Psychiatric
      comorbidity was assessed by a psychiatrist using a structured clinical interview.
      Quality of life (QoL), pain rating and medication/drug/alcohol usage were
      measured by validated questionnaires: SF-36, NRS, DUDIT and AUDIT. Concerning
      physical functioning and sick leave, a comparison was made with data from the
      Swedish Quality Register Registry for pain rehabilitation (SQRP). RESULTS: The
      cohort consisted of 61% women and the average age was 45 (range 20-70) years. For
      this cohort, 74% reported being on sick leave or disability-pension. In the SQRP
      59% were on sick leave at the time they entered the rehabilitation programmes
      [1]. On average, the study-population reported 22 symptoms other than pain, to be
      at a high rate of severity. Patients treated in conventional pain-rehabilitation
      programmes reported a mean of 10 symptoms in average. Symptoms reported with the
      highest frequency (>80%), were lethargy, tiredness, headache and difficulties
      concentrating. Seventy-six percent were diagnosed with a psychiatric disorder.
      Sixty-nine fulfilled the criteria for depression or depression/anxiety disorder
      despite that most (65%) were treated with psychotropic medication. Alcohol/drug
      abuse was minimal. Seventy-one percent were on opioids but the doses were
      moderate (<100mg) MEq. The pain rating was >=7 (out of a maximum of 10) for 60%
      of the patients. CONCLUSION: This study describes what makes the subgroup of pain
      patients most affected by their pain special according to associated factors and
      comorbidity We found that they were distinguished by a high degree of psychiatric
      comorbidity, low physical functioning and extreme levels of symptom
      preoccupation/hypervigilance. Many severe symptoms additional to pain (e.g.
      depression/anxiety, tiredness, disturbed sleep, lack of concentration,
      constipation) were reported. The group seems hypervigilant, overwhelmed with a
      multitude of different symptoms on a high severity level. IMPLICATIONS: When
      treating this complex group, the expressions of the illness can act as obstacles
      to achieve successful treatment outcomes. The study provides evidence based
      information, for a better understanding of the needs concerning these pain
      patients. Our result indicates that parallel assessment and treatment of
      psychiatric comorbidities and sleep disorders combined with traditional
      rehabilitation, i.e. physical activation and cognitive reorganization are
      imperative for improved outcomes.

PMID- 29032351
TI  - Testosterone-induced modulation of peroxisomal morphology and peroxisome-related
      gene expression in brown trout (Salmo trutta f. fario) primary hepatocytes.
AB  - Disruption of androgenic signaling has been linked to possible cross-modulation
      with other hormone-mediated pathways. Therefore, our objective was to explore
      effects caused by testosterone - T (1, 10 and 50MUM) in peroxisomal signaling of
      brown trout hepatocytes. To study the underlying paths involved, several co
      exposure conditions were tested, with flutamide - F (anti-androgen) and ICI
      182,780 - ICI (anti-estrogen). Molecular and morphological approaches were both
      evaluated. Peroxisome proliferator-activated receptor alpha (PPARalpha), catalase
      and urate oxidase were the selected targets for gene expression analysis. The
      vitellogenin A gene was also included as a biomarker of estrogenicity. Peroxisome
      relative volumes were estimated by immunofluorescence, and transmission electron
      microscopy was used for qualitative morphological control. The single exposures
      of T caused a significant down-regulation of urate oxidase (10 and 50MUM) and a
      general up-regulation of vitellogenin. A significant reduction of peroxisome
      relative volumes and smaller peroxisome profiles were observed at 50MUM. Co
      administration of T and ICI reversed the morphological modifications and
      vitellogenin levels. The simultaneous exposure of T and F caused a significant
      and concentration-dependent diminishing in vitellogenin expression. Together, the
      findings suggest that in the tested model, T acted via both androgen and estrogen
      receptors to shape the peroxisomal related targets.

PMID- 29032352
TI  - Physiological impacts of acute Cu exposure on deep-sea vent mussel Bathymodiolus
      azoricus under a deep-sea mining activity scenario.
AB  - Over the past years, several studies have been dedicated to understanding the
      physiological ability of the vent mussel Bathymodiolus azoricus to overcome the
      high metal concentrations present in their surrounding hydrothermal environment.
      Potential deep-sea mining activities at Azores Triple junction hydrothermal vent
      deposits would inevitably lead to the emergence of new fluid sources close to
      mussel beds, with consequent emission of high metal concentrations and potential
      resolubilization of Cu from minerals formed during the active phase of the vent
      field. Copper is an essential metal playing a key role in the activation of
      metalloenzymes and metalloproteins responsible for important cellular metabolic
      processes and tissue homeostasis. However, excessive intracellular amounts of
      reactive Cu ions may cause irreversible damages triggering possible cell
      apoptosis. In the present study, B. azoricus was exposed to increasing
      concentrations of Cu for 96h in conditions of temperature and hydrostatic
      pressure similar to those experienced at the Lucky Strike hydrothermal vent
      field. Specimens were kept in 1L flasks, exposed to four Cu concentrations:
      0MUg/L (control), 300, 800 and 1600MUg/L and pressurized to 1750bar. We addressed
      the question of how increased Cu concentration would affect the function of
      antioxidant defense proteins and expression of antioxidant and immune-related
      genes in B. azoricus. Both antioxidant enzymatic activities and gene expression
      were examined in gills, mantle and digestive gland tissues of exposed vent
      mussels. Our study reveals that stressful short-term Cu exposure has a strong
      effect on molecular metabolism of the hydrothermal vent mussel, especially in
      gill tissue. Initially, both the stress caused by unpressurization or by Cu
      exposure was associated with high antioxidant enzyme activities and tissue
      specific transcriptional up-regulation. However, mussels exposed to increased Cu
      concentrations showed both antioxidant and immune-related gene suppression. Under
      a mining activity scenario, the release of an excess of dissolved Cu to the vent
      environment may cause serious changes in cellular defense mechanisms of B.
      azoricus. This outcome, while adding to our knowledge of Cu toxicity, highlights
      the potentially deleterious impacts of mining activities on the physiology of
      deep-sea organisms.

PMID- 29032353
TI  - Rates of Joint Replacement Surgery in New Zealand, 1999-2015: A Comparison of
      Rheumatoid Arthritis and Osteoarthritis.
AB  - OBJECTIVE: To determine rates of joint replacement for people with rheumatoid
      arthritis (RA) and osteoarthritis (OA) and to examine the characteristics of
      those receiving elbow replacements. METHODS: Data were extracted from the New
      Zealand Joint Registry from 1999 to 2015 and annual rates calculated. RESULTS:
      Rates of joint replacement increased over time for OA but not RA. Elbow
      replacement was the only procedure performed more commonly in RA. CONCLUSION:
      There has been a substantial increase in joint replacement for OA in New Zealand.
      For RA, where access to biologics has been limited to those with erosions, joint
      replacement rates have not declined, with the exception of elbow replacements.

PMID- 29032354
TI  - Exercise for Hand Osteoarthritis: A Cochrane Systematic Review.
AB  - OBJECTIVE: To assess the benefits and harms of exercise compared with other
      interventions, including placebo or no intervention, in people with hand
      osteoarthritis (OA). METHODS: Systematic review using Cochrane Collaboration
      methodology. Six electronic databases were searched up until September 2015.
      INCLUSION CRITERIA: randomized or controlled clinical trials comparing
      therapeutic exercise versus no exercise, or comparing different exercise
      programs. MAIN OUTCOMES: hand pain, hand function, finger joint stiffness,
      quality of life, adverse events, and withdrawals because of adverse effects. Risk
      of bias and quality of the evidence were assessed. RESULTS: Seven trials were
      included in the review, and up to 5 trials (n = 381) were included in the pooled
      analyses with data from postintervention. Compared to no exercise, low-quality
      evidence indicated that exercise may improve hand pain [5 trials, standardized
      mean difference (SMD) -0.27, 95% CI -0.47 to -0.07], hand function (4 trials, SMD
      -0.28, 95% CI -0.58 to 0.02), and finger joint stiffness (4 trials, SMD -0.36,
      95% CI -0.58 to -0.15) in people with hand OA. Quality of life was evaluated by 1
      study (113 participants) showing very low-quality evidence for no difference.
      Three studies reported on adverse events, which were very few and not severe.
      CONCLUSION: Pooled results from 5 studies with low risk of bias showed low
      quality evidence for small to moderate beneficial effects of exercise on hand
      pain, function, and finger joint stiffness postintervention. Estimated effect
      sizes were small, and whether they represent a clinically important change may be
      debated.

PMID- 29032357
TI  - Actin assembly mechanisms at a glance.
AB  - The actin cytoskeleton and associated motor proteins provide the driving forces
      for establishing the astonishing morphological diversity and dynamics of
      mammalian cells. Aside from functions in protruding and contracting cell
      membranes for motility, differentiation or cell division, the actin cytoskeleton
      provides forces to shape and move intracellular membranes of organelles and
      vesicles. To establish the many different actin assembly functions required in
      time and space, actin nucleators are targeted to specific subcellular
      compartments, thereby restricting the generation of specific actin filament
      structures to those sites. Recent research has revealed that targeting and
      activation of actin filament nucleators, elongators and myosin motors are tightly
      coordinated by conserved protein complexes to orchestrate force generation. In
      this Cell Science at a Glance article and the accompanying poster, we summarize
      and discuss the current knowledge on the corresponding protein complexes and
      their modes of action in actin nucleation, elongation and force generation.

PMID- 29032358
TI  - A rim-and-spoke hypothesis to explain the biomechanical roles for cytoplasmic
      intermediate filament networks.
AB  - Textbook images of keratin intermediate filament (IF) networks in epithelial
      cells and the functional compromization of the epidermis by keratin mutations
      promulgate a mechanical role for this important cytoskeletal component. In
      stratified epithelia, keratin filaments form prominent radial spokes that are
      focused onto cell-cell contact sites, i.e. the desmosomes. In this Hypothesis, we
      draw attention to a subset of keratin filaments that are apposed to the plasma
      membrane. They form a rim of filaments interconnecting the desmosomes in a
      circumferential network. We hypothesize that they are part of a rim-and-spoke
      arrangement of IFs in epithelia. From our review of the literature, we extend
      this functional role for the subplasmalemmal rim of IFs to any cell, in which
      plasma membrane support is required, provided these filaments connect directly or
      indirectly to the plasma membrane. Furthermore, cytoplasmic IF networks
      physically link the outer nuclear and plasma membranes, but their participation
      in mechanotransduction processes remain largely unconsidered. Therefore, we also
      discuss the potential biomechanical and mechanosensory role(s) of the cytoplasmic
      IF network in terms of such a rim (i.e. subplasmalemmal)-and-spoke arrangement
      for cytoplasmic IF networks.

PMID- 29032360
TI  - Management of mature athletes with cardiovascular conditions.

PMID- 29032361
TI  - Myocardial biopsy: techniques and indications.

PMID- 29032359
TI  - Nanodisc-based kinetic assays reveal distinct effects of phospholipid headgroups
      on the phosphoenzyme transition of sarcoplasmic reticulum Ca2+-ATPase.
AB  - Sarco(endo)plasmic reticulum Ca2+-ATPase catalyzes ATP-driven Ca2+ transport from
      the cytoplasm to the lumen and is critical for a range of cell functions,
      including muscle relaxation. Here, we investigated the effects of the headgroups
      of the 1-palmitoyl-2-oleoyl glycerophospholipids phosphatidylcholine (PC),
      phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylglycerol
      (PG) on sarcoplasmic reticulum (SR) Ca2+-ATPase embedded into a nanodisc, a lipid
      bilayer construct harboring the specific lipid. We found that Ca2+-ATPase
      activity in a PC bilayer is comparable with that of SR vesicles and is suppressed
      in the other phospholipids, especially in PS. Ca2+ affinity at the high-affinity
      transport sites in PC was similar to that of SR vesicles, but 2-3-fold reduced in
      PE and PS. Ca2+ on- and off-rates in the non-phosphorylated ATPase were markedly
      reduced in PS. Rate-limiting phosphoenzyme (EP) conformational transition in 0.1
      m KCl was as rapid in PC as in SR vesicles, but slowed in other phospholipids,
      especially in PS. Using kinetic plots of the logarithm of rate versus the square
      of mean activity coefficient of solutes in 0.1-1 m KCl, we noted that PC is
      optimal for the EP transition, but PG and especially PS had markedly unfavorable
      electrostatic effects, and PE exhibited a strong non-electrostatic restriction.
      Thus, the major SR membrane lipid PC is optimal for all steps and, unlike the
      other headgroups, contributes favorable electrostatics and non-electrostatic
      elements during the EP transition. Our analyses further revealed that the surface
      charge of the lipid bilayer directly modulates the transition rate.

PMID- 29032362
TI  - Simple six-item clinical score improves risk prediction capability of stress
      echocardiography.
AB  - OBJECTIVES: To assess the value of a simple score integrating non-ischaemia
      related variables in expanding the wall motion abnormalities risk power during
      stress echocardiography (SE). METHODS: Study includes 14 279 patients who
      underwent SE for evaluation of coronary artery disease. All-cause death was the
      end point. Patients were randomly divided into the modelling and validation group
      of equal size. In the modelling group, multivariate analysis was conducted using
      clinical, rest and SE data, and a score was obtained from the number of non
      ischaemia-related independent prognostic predictors. The score prognostic
      capability was compared in both groups. RESULTS: During a median follow-up of 31
      months, 1230 patients died: 622 (9%) in the modelling and 608 (9%) in the
      validation group (p=0.68). Independent predictors of mortality were ischaemia at
      SE (HR 1.77, 95% CI 1.49 to 2.12; p<0.0001) and six other parameters: age>65
      years, wall motion at rest, diabetes, left bundle branch block, anti-ischaemic
      therapy and male sex. Risk score resulted prognostically effective in the
      modelling and validation groups, both with and without inducible ischaemia
      subset. When risk score was included in the multivariate analysis, besides
      ischaemia at SE it was the only independent predictor of mortality in the
      modelling (HR 1.70, 95% CI 1.60 to 1.82; p<0.0001), in the validation (HR 1.77,
      95% CI 1.65 to 1.90; p<0.0001) and in the overall group (HR 1.73, 95% CI 1.66 to
      1.82; p<0.0001). CONCLUSIONS: Simple clinical variables may be able to optimise
      SE risk stratification.

PMID- 29032363
TI  - 25-year-old man with chest pain.
AB  - CLINICAL INTRODUCTION: A 25-year-old man presented with complaints of acute-onset
      chest pain for 2 hours associated with diaphoresis and generalised weakness. He
      had history of smoking for 10 years. There was no history of hypertension,
      diabetes, family history of premature coronary artery disease or drug abuse. On
      evaluation, his heart rate was 76/min, blood pressure 130/90 mm Hg and oxygen
      saturation 97% on room air. Cardiovascular examination was normal. The ECG is
      shown in figure 1.heartjnl;104/1/72/F1F1F1Figure 1.

PMID- 29032364
TI  - Gymnastics injury incidence during the 2008, 2012 and 2016 Olympic Games:
      analysis of prospectively collected surveillance data from 963 registered
      gymnasts during Olympic Games.
AB  - OBJECTIVE: To determine the incidence and characteristics of injuries in female
      and male gymnastics disciplines (artistic, rhythmic and trampoline) during three
      Olympic Games with a view to ultimately improving injury prevention. METHODS: The
      National Olympic Committee's head physicians and the medical teams of the Local
      Organising Committee of the Olympic Games reported daily the occurrence (or non
      occurrence) of newly sustained injuries in artistic, rhythmic and trampoline
      gymnastics on a standardised report form during the 2008, 2012 and 2016 Summer
      Olympic Games. RESULTS: During the three Olympic Games, 81 injuries were reported
      in a total of 963 registered gymnasts, corresponding to an incidence of 84
      injuries (95% CI 67 to 102) per 1000 registered gymnasts, with no difference in
      injury incidence between female and male gymnasts. Thirty-eight per cent of
      injuries led to time-loss from sport. The most frequent injury location and
      injury type were the ankle (22%) and sprain (35%), respectively. The most common
      diagnosis was ankle sprain (14% of all injuries and 23% of time-loss injuries).
      The injury incidence was highest in female (107+/-35) and male artistic
      gymnastics (83+/-32), followed by female rhythmic gymnastics (73+/-30), and lower
      in male (63+/-69) and female (43+/-43) trampoline gymnastics. CONCLUSIONS:
      Research should focus on preventing injuries in artistic gymnastics and of the
      condition of ankle sprain. Injury surveillance studies should be continued during
      major championships and throughout the entire competitive season as the Olympic
      Games provides only a snapshot (although an important one).

PMID- 29032365
TI  - How does academic achievement relate to cardiorespiratory fitness, self-reported
      physical activity and objectively reported physical activity: a systematic review
      in children and adolescents aged 6-18 years.
AB  - OBJECTIVE: This report aimed to systematically review the evidence for a
      differential association between objective and self-reported physical activity
      and cardiorespiratory fitness on academic achievement. DESIGN: Systematic review.
      DATA SOURCES: Studies were identified from searches in Embase, Education
      Resources Information Center, PubMed, PsycINFO, SPORTdiscus and Web of Science
      databases from January 2000 to December 2016. ELIGIBILITY CRITERIA FOR SELECTING
      STUDIES: Eligibility criteria included cross-sectional, longitudinal and
      interventional study designs. Outcomes included students' school grade or a
      standardised test or measure of academic achievement. Explanatory variables were
      cardiorespiratory fitness and objective and self-reported physical activity.
      Inclusion criteria included school-aged children and adolescents aged-18 years
      (or students from primary to secondary school when student's participants age was
      not described) and articles published in English, Portuguese or Spanish. RESULTS:
      A total of 51 articles met inclusion criteria: 41 cross-sectional, 2 intervention
      and 8 longitudinal studies. Results from 11 studies were inconsistent regarding
      the relationship between objectively measured physical activity and academic
      achievement. Ten of the 16 articles reported positive associations between self
      reported physical activity and academic achievement. From the 22 studies that
      analysed the relationship between cardiorespiratory fitness and academic
      achievement, it was verified that they all generally support the beneficial
      effect of cardiorespiratory fitness on students' academic achievement.
      CONCLUSION: Higher cardiorespiratory fitness may be important to enhance children
      and adolescents' health and, additionally, academic achievement. Due to a lack of
      consensus across studies, methodological issues associated with the assessment of
      physical activity should be considered when investigating physical activity and
      academic achievement.

PMID- 29032366
TI  - From assistive to enhancing technology: should the treatment-enhancement
      distinction apply to future assistive and augmenting technologies?
AB  - The treatment-enhancement distinction is often used to delineate acceptable and
      unacceptable medical interventions. It is likely that future assistive and
      augmenting technologies will also soon develop to a level that they might be
      considered to provide users, in particular those with disabilities, with
      abilities that go beyond natural human limits, and become in effect an enhancing
      technology. In this paper, we describe how this process might take place, and
      discuss the moral implications of such developments. We argue that such
      developments are morally acceptable and indeed desirable.

PMID- 29032367
TI  - A flimsy case for the use of non-human primates in research: a reply to Arnason.

PMID- 29032368
TI  - The ethical justification for the use of non-human primates in research: the
      Weatherall report revisited.
AB  - The Weatherall report on the use of non-human primates in research was published
      in 2006. Its main conclusion was that there is a strong scientific case for the
      use of non-human primates in some cases, but the report stressed the importance
      of evaluating each case in the light of the availability of alternatives. In
      addition to arguing for the scientific necessity of using non-human primates in
      research, the report also provided an ethical justification. As could be
      expected, the report was harshly criticised by animal rights groups, but in the
      academic literature, only two critical replies appeared. In what follows, I will
      describe the ethical justification for non-human primate research as it is laid
      out in the Weatherall report and then consider the criticism in the academic
      literature. I conclude that the report's ethical justification for the use of non
      human primates in research, in particular in basic neuroscientific research, has
      not been convincingly challenged by its critics. Since the criticism of the
      report is limited and represents only a small part of the academic discussion
      about the use of non-human primates in research, and a still smaller part of the
      ethical discussion about animal research, it is important that the discussion
      continue both at the academic and social level.

PMID- 29032369
TI  - Patricia Keely (1963-2017).

PMID- 29032370
TI  - An immunofluorescence assay for extracellular matrix components highlights the
      role of epithelial cells in producing a stable, fibrillar extracellular matrix.
AB  - Activated fibroblasts are considered major drivers of fibrotic disease
      progression through the production of excessive extracellular matrix (ECM) in
      response to signals from damaged epithelial and inflammatory cells. Nevertheless,
      epithelial cells are capable of expressing components of the ECM, cross-linking
      enzymes that increase its stability and are sensitive to factors involved in the
      early stages of fibrosis. We therefore wanted to test the hypothesis that
      epithelial cells can deposit ECM in response to stimulation in a comparable
      manner to fibroblasts. We performed immunofluorescence analysis of components of
      stable, mature extracellular matrix produced by primary human renal proximal
      tubular epithelial cells and renal fibroblasts in response to cytokine
      stimulation. Whilst fibroblasts produced a higher basal level of extracellular
      matrix components, epithelial cells were able to deposit significant levels of
      fibronectin, collagen I, III and IV in response to cytokine stimulation. In
      response to hypoxia, epithelial cells showed an increase in collagen IV
      deposition but not in response to the acute stress stimuli aristolochic acid or
      hydrogen peroxide. When epithelial cells were in co-culture with fibroblasts we
      observed significant increases in the level of matrix deposition which could be
      reduced by transforming growth factor beta (TGF-beta) blockade. Our results
      highlight the role of epithelial cells acting as efficient producers of stable
      extracellular matrix which could contribute to renal tubule thickening in
      fibrosis.

PMID- 29032371
TI  - Reassessing the significance of the PAH c.158G>A (p.Arg53His) variant in patients
      with hyperphenylalaninemia.
AB  - BACKGROUND: The accurate interpretation of sequence variation is critical for
      successful molecular diagnoses. It is also fundamental to the accurate diagnosis
      and treatment of phenylketonuria (PKU). This study aims to evaluate the
      significance of the c.158G>A (p.Arg53His) variant in the PAH gene, which was
      previously reported to be a pathogenic mutation that results in decreased
      phenylalanine hydroxylase enzyme activity in hyperphenylalaninemia (HPA)
      patients. METHODS: Seven unrelated Korean patients with HPA genotyped with the
      c.158G>A variant were included in this study. The variant c.158G>A was classified
      by the standards and guidelines for the interpretation of sequence variants by
      the American College of Medical Genetics and Genomics and the Association for
      Molecular Pathology. RESULTS: By both directly collecting genetic data and
      comprehensively reviewing the existing literature, we found that this variant is
      more appropriately classified as "Likely benign" rather than pathogenic. The
      allele's frequency is 2.57% in the general Korean population, which was greater
      than expected for phenylketonuria. This variant was observed to be homozygous in
      healthy subjects and was also observed in cis with other pathogenic variants. It
      is common in East Asian populations (especially in Koreans) compared to Western
      populations. There is a possibility that it causes decreased enzyme activity
      without leading to the full pathology of phenylketonuria. CONCLUSIONS: This study
      expands our understanding of the consequences of variation in PAH and its
      relationship to HPA.

PMID- 29032372
TI  - Parenchymal-Sparing Surgery for the Surgical Treatment of Multiple Colorectal
      Liver Metastases Is a Safer Approach than Major Hepatectomy Not Impairing
      Patients' Prognosis: A Bi-Institutional Propensity Score-Matched Analysis.
AB  - BACKGROUND: The performance of parenchymal-sparing hepatectomy (PSH) versus major
      hepatectomy (MH) in patients with multiple colorectal liver metastases (CLM) is a
      matter that is yet debated. We investigated the outcome of patients with multiple
      CLM undergoing PSH instead of MH. METHODS: Databases at 2 institutions were
      reviewed. A propensity score-matched analysis was applied. Among 554 patients,
      110 undergoing PSH and 110 undergoing MH were matched. They were similar in
      baseline characteristics, comorbidity, and tumor features. Primary outcomes were
      short- and long-term outcomes. RESULTS: Morbidity was significantly higher in the
      MH group, while mortality was not significantly different. There were no
      differences in free-margins width, but a trend of increased survival was seen in
      the PSH group with a median advantage of 6 months over the MH group. Among the
      prognostic factors, the T status (hazard ratio [HR] 2.6; p = 0.001), the N status
      (HR 2.9; p = 0.001), the timing of CLM diagnosis (HR 2.1; p = 0.002), the tumor
      number (HR 2.0; p = 0.001), the tumor size (HR 2.2; p = 0.015), and the neo
      adjuvant chemotherapy (HR 1.7; p = 0.023) were found to be statistically and
      independently significant for survival. CONCLUSIONS: PSH conveys advantage over
      MH in terms of decreased postoperative morbidity, and a trend of survival
      benefit. PSH should be considered a suitable alternative to MH whenever it is
      technically feasible.

PMID- 29032373
TI  - Differentiating Clostridium difficile Colitis from Clostridium difficile
      Colonization in Ulcerative Colitis: A Role for Procalcitonin.
AB  - BACKGROUND/AIMS: Clostridium difficile infection (CDI) frequently complicates
      ulcerative colitis (UC) and can mimic disease flare. Differentiating UC flare
      from CDI remains a clinical challenge, particularly due to C. difficile
      colonization. Procalcitonin (PCT) is a serum biomarker for bacterial infections.
      We hypothesized that PCT would differentiate acute CDI from UC flare and C.
      difficile colonization. METHODS: A single-center prospective cohort study was
      conducted from 2013 to 2016. All UC patients with a stool sample for C. difficile
      testing were eligible. A total of 117 patients were enrolled, while 20 were
      excluded. Chart review was performed. RESULTS: Among 27 patients with CDI, median
      PCT was 60.7 (range 26-560.6) pg/mL, while among 90 patients without CDI, median
      PCT was 56.7 (range 25.1-2,252) pg/mL (p = 0.9). It was found that 14 patients
      with CDI responded completely to C. difficile treatment (CDI-R), while 8 patients
      did not and were diagnosed with UC flare (CDI-NR). For CDI-R, median PCT was
      104.5 (range 26.3-560.6), compared to 40.3 (range 26.0-116.3) for CDI-NR (p =
      0.036). CONCLUSIONS: In UC patients presenting with diarrhea, serum PCT was not
      significantly higher in UC patients with positive C. difficile testing. However,
      PCT was significantly elevated in CDI-R versus CDI-NR, suggesting that PCT may
      have utility in making this discrimination.

PMID- 29032374
TI  - The ALPPS Approach for Colorectal Liver Metastases: Impact of KRAS Mutation
      Status in Survival.
AB  - BACKGROUND/AIMS: Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations
      influence survival after hepatectomy for colorectal liver metastases (CRLM).
      However, their prognostic significance has never been evaluated in patients who
      undergo Associating Liver Partition and Portal vein occlusion for Staged
      hepatectomy (ALPPS). METHODS: Between June 2011 and March 2016, 26 patients
      underwent ALPPS for CRLM. Complications were classified according to the Clavien
      Dindo classification. Bi- and multivariate cox analyses were performed to
      evaluate variables potentially associated with survival. RESULTS: Overall,
      morbidity grade >=3a and 90-day mortality were 38.5 and 0%, respectively. The
      median follow-up from the time of discharge was 21.5 months (interquartile range
      9.6-35.6). One- and 3-year overall survival (OS) was 83.4 and 48.9%,
      respectively. Patients with mutated (MT) KRAS had a median OS of 15.3 vs. 38.3
      months for those with wild-type (WT) KRAS (p < 0.0001). Median disease-free
      survival was 7.9, 5.6 vs. 12.3 months for MT and WT KRAS, respectively (p =
      0.023). KRAS mutation was found to be an independent risk factor for OS (hazard
      ratio 7.15, 95% CI 1.50-34.11; p = 0.014). CONCLUSION: KRAS mutation is an
      independent predictor of poor survival after ALPPS. This finding will help to
      optimize patient selection, both avoiding futile surgical indication and
      maximizing the benefit for patients with extensive disease who are otherwise
      subjected to high-risk aggressive surgery.

PMID- 29032375
TI  - Erratum.

PMID- 29032376
TI  - Impact of Uric Acid Levels on Kidney Disease Progression.
AB  - BACKGROUND: Hyperuricemia is associated with the progression of chronic kidney
      disease (CKD), but it is not known whether the relationship is causal. We
      examined the association of hyperuricemia and uric acid lowering therapy (UALT)
      with progression of CKD in patients with CKD 3 and 4 in the Cleveland Clinic CKD
      registry. METHODS: We included 1,676 patients with CKD stages 3 and 4 from Ohio,
      who had measured their uric acid (UA) levels a year prior to the recording of the
      second eGFR <60 mL/min/1.73 m2, and follow-up eGFR, between 2005 and 2009. Our
      primary composite outcome included a 50% drop in eGFR or progression to ESRD.
      Secondary outcomes included the rate of decline in eGFR, all-cause mortality,
      progression to ESRD, and a composite measure of progression to ESRD or death. We
      assessed the association between UA, UALT, and outcomes using Cox models and
      competing risks regression models. RESULTS: In multivariable models, higher UA
      was associated with the composite endpoint, but it reached statistical
      significance only in the 4th quartile (>=8.9 mg/dL). Receipt of UALT was
      significantly associated with increased risk of the composite outcome. Neither UA
      nor UALT (considered a time-dependent covariate) was significantly associated
      with mortality. The inference was similar for UA as high vs. low, quartiles, or
      continuous. Similarly, neither high UA nor UALT were significantly associated
      with ESRD, the composite of ESRD and mortality, or eGFR decline. CONCLUSIONS:
      Hyperuricemia is associated with increased risk of progression to ESRD in
      patients with CKD stages 3 and 4, but UALT does not ameliorate the risk,
      suggesting that the relationship is not causal.

PMID- 29032377
TI  - MicroRNA-210 Modulates the Cellular Energy Metabolism Shift During H2O2-Induced
      Oxidative Stress by Repressing ISCU in H9c2 Cardiomyocytes.
AB  - BACKGROUND/AIMS: The myocardial energy metabolism shift is one of the most
      important pathological features of ischemic heart disease (IHD). Although several
      microRNAs (miRs) are involved in the regulation of myocardial energy metabolism,
      their exact effects and underlying mechanisms remain unclear. The aim of this
      study was to investigate whether microRNA(miR-210) regulates the energy
      metabolism shift during oxidative stress in H9c2 cardiomyocytes. METHODS: Cell
      survival was analyzed via CCK assay. The energy metabolism shift was detected by
      lactate assay, ATP assay and RT2 profiler glucose metabolism PCR array. Protein
      and mRNA expression levels were determined by western blot and qPCR. We also used
      kits to detect the activity of Complex I, Sirt3 and the NAD+/NADH ratio. RESULTS:
      We determined that miR-210 promoted the energy metabolism shift. The iron-sulfur
      cluster assembly protein (ISCU) was a target of miR-210. Additionally, we
      detected the activity of complex I and found that miR-210 inhibits mitochondrial
      respiration. Interestingly, miR-210 may also indirectly regulate SIRT3 by
      regulating ISCU. CONCLUSION: Our results confirm that miR-210 is essential and
      sufficient for modulating the cellular energy metabolism shift during H2O2
      induced oxidative stress in H9c2 cardiomyocytes by targeting ISCU.

PMID- 29032378
TI  - Survey Results of the Expert Meeting on Laparoscopic Living Donor Hepatectomy and
      Literature Review.
AB  - BACKGROUND: Because laparoscopic donor surgery has been successful in pediatric
      living donor liver transplantation, its application is expanding to right
      hepatectomy. However, there is no consensus on the indications for laparoscopic
      donor hepatectomy or on the details of the surgical technique. OBJECTIVE: To
      evaluate the current status of laparoscopic donor hepatectomy and to summarize
      the expert opinion on it. METHODS: Before the expert meeting on September 8,
      2016, in Seoul, Korea, a survey was undertaken from expert liver surgeons from
      around the world. RESULTS: Fifteen of 17 (88.2%) surgeons responded to the
      survey. The selection criteria for laparoscopic donor surgery are stricter than
      for open surgery in terms of the anatomy, remnant liver volume, and recipient's
      condition. There is no consensus on the instruments or equipment used. A
      literature review of laparoscopic donor hepatectomy showed that the use of this
      method is increasing and the short-term outcomes are similar to those of open
      surgery. CONCLUSIONS: This survey and literature review show that laparoscopic
      donor hepatectomy is performed by experienced surgeons in selected cases, and
      that its incidence is increasing worldwide.

PMID- 29032379
TI  - Oral Bicarbonate Slows Decline of Residual Renal Function in Peritoneal Dialysis
      Patients.
AB  - BACKGROUND/AIMS: Metabolic acidosis is a common consequence of end-stage renal
      disease (ESRD) which may result in a substantial adverse outcome. The effect of
      oral bicarbonate on the preservation of residual renal function (RRF) in
      peritoneal dialysis (PD) patients has been rarely reported. METHODS: We randomly
      assigned 40 continuous ambulatory peritoneal dialysis (CAPD) patients to the oral
      bicarbonate group or placebo group at a 1: 1 ratio. All enrollments were followed
      for a duration of 104 weeks. We took residual creatinine clearance (CCr), a
      measure of residual renal function (RRF), as the primary outcome. Residual CCr
      was calculated as the average of urea and creatinine clearance from a 24-hour
      urine collection. RESULTS: Thirteen patients in the placebo group and 15 patients
      in the treatment group completed the 104 weeks of follow-up with a comparable
      dropout rate (placebo group: 35% vs treatment group: 25%). Compared with the
      placebo group, serum bicarbonate in treatment group was significantly increased
      at each time point, and oral bicarbonate resulted in a slower declining rate of
      residual CCr (F=5.113, p=0.031). Baseline residual CCr at enrollment also had a
      significant effect on residual CCr (F=168.779, P<0.001). Charlson Comorbidity
      Index which was adopted to calculate a comorbidity score had no significant
      effect on residual CCr loss (F=0.168, P=0.685). CONCLUSION: Oral bicarbonate may
      have a RRF preserving effect in CAPD patients, and a normal to high level of
      serum bicarbonate (>=24mmol/L) may be appropriate for RRF preservation.

PMID- 29032380
TI  - The Landscape of Circulating Tumor Cell Research in the Context of Epithelial
      Mesenchymal Transition.
AB  - The metastatic spread of cancer accounts for the vast majority of cancer-related
      deaths. It is mediated by tumor cells circulating in blood (called circulating
      tumor cells, CTCs), which escaped from their established niches. CTCs give a
      unique opportunity to look into the metastatic cascade and to study the molecular
      processes supporting the spread of tumor cells throughout the body. As current
      therapies are not sufficiently effective in treating metastatic disease, it is
      important to determine cellular and molecular features of cancer cells that
      "seed" new tumors in distant organs at early stages. In this review we focus on
      the role of the epithelial-mesenchymal transition program in providing a survival
      advantage to metastasizing tumor cells, especially CTCs, and put it in the
      context of clinical findings.

PMID- 29032381
TI  - Analysis of Correlation Between Vertebral Endplate Change and Lumbar Disc
      Degeneration.
AB  - BACKGROUND To evaluate the correlation between vertebral endplate change and the
      level of lumbar disc degeneration via magnetic resonance imaging (MRI). MATERIAL
      AND METHODS A total of 345 patients who were recruited from our hospital from May
      2012 to May 2016 were evaluated for the presence of intervertebral disc
      degeneration or herniation. The degree of degeneration was assessed according to
      Pfirrmann grade. Vertebral endplate change was evaluated based on the endplate
      concave angle (ECA), and Modic change on sagittal MRI. The correlation between
      ECA and lumbar disc degeneration or Modic change and lumbar disc degeneration was
      analyzed. RESULTS The results showed that there was no statistically significant
      difference in comparison of the ECAs in adjacent L3-5 vertebra between males and
      females. With the aggravation in degenerative changes of L3-5 discs, the ECAs of
      adjacent L3 superior endplate, L4 inferior and superior endplates and L5 inferior
      endplate were gradually enlarged, indicating the positive correlation between the
      lumbar disc degeneration and ECAs. The rate of Modic change in females was higher
      than that in males without a statistically significant difference. Area of Modic
      change was positively correlated with the degree of lumbar disc degeneration.
      Additionally, we also identified the positive correlation between the rate of
      Modic change and the degree of lumbar disc degeneration. CONCLUSIONS Endplate
      angle and lumbar disc degeneration are positively correlated. The endplates and
      endplate signal changes can reflect the degree of disc degeneration and Modic
      changes can reflect the rate of clinical lumbar disc degeneration degree.

PMID- 29032383
TI  - Stigma in the addicted person.
AB  - Editorial of vol. 29-4.

PMID- 29032382
TI  - Angiotensin-Converting Enzyme Gene Deletion Polymorphism is Associated with Lymph
      Node Metastasis in Colorectal Cancer Patients in a Chinese Population.
AB  - BACKGROUND The purpose of this study was to assess the effect of angiotensin
      converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism on the risk of
      lymph node metastasis (LNM) in colorectal cancer (CRC) patients. MATERIAL AND
      METHODS We enrolled 146 CRC patients and 106 healthy controls in this study. ACE
      gene I/D polymorphism was genotyped by polymerase chain reaction (PCR). Hardy
      Weinberg equilibrium (HWE) was used to assess the goodness of fit of the
      genotypes. chi2 test was used to calculate the differences of genotype and allele
      distributions. Odds ratios (ORs) with corresponding 95% confidence intervals (95%
      CIs) were used to analyze the association between ACE I/D polymorphism and LNM in
      CRC patients. RESULTS Insertion/deletion (ID) and deletion/deletion (DD)
      genotypes were frequently observed in CRC patients, but only DD genotype and D
      allele were related to the susceptibility of CRC (P=0.038, OR=2.158, 95%CI=1.039
      4.480; P=0.026, OR=1.501, 95%CI=1.048-2.150). DD genotype and D allele also
      increased the risk of LNM in CRC patients (P=0.028, OR=2.844, 95%CI=1.107-7.038;
      P=0.026, OR=1.692, 95%CI=1.063-2.693). CONCLUSIONS DD genotype and D allele of
      ACE gene I/D polymorphism might increase the risk of LNM in CRC patients.

PMID- 29032384
TI  - Proton pump inhibitor use and the risk of osteoporosis and fracture in stroke
      patients: a population-based cohort study.
AB  - : A considerable proportion of stroke survivors are prescribed with proton pump
      inhibitors (PPIs). Our study indicated that PPI use is associated with an
      increased risk of osteoporosis, hip fracture, and vertebral fracture in stroke
      patients. The risk tends to increase as the cumulative doses of PPIs increase.
      INTRODUCTION: A considerable proportion of stroke survivors are prescribed with
      proton pump inhibitors (PPIs). Our study investigated the association between PPI
      use and the risk of osteoporosis and fracture among stroke survivors. METHODS: A
      population-based propensity-matched retrospective cohort study was conducted
      using the National Health Insurance Research Database in Taiwan. Patients
      diagnosed with a new stroke between 2000 and 2012 were identified. After
      propensity score matching, 10,596 patients were enrolled, and 5298 patients were
      each assigned to the PPI user and non-user groups. Hazard ratios (HRs) were
      calculated for the risk of osteoporosis, hip fracture, and vertebral fractures
      according to PPI use or non-use. Sensitivity analyses were conducted to evaluate
      the dose effects of PPI. RESULTS: PPI use after stroke was associated with an
      increased risk of osteoporosis, hip fracture, or vertebral fracture, with an
      adjusted HR (aHR) of 1.28 (P < 0.001). The aHRs were also significant for each
      outcome: osteoporosis, 1.26 (P < 0.001); hip fracture, 1.18 (P = 0.048);
      vertebral fracture, 1.33 (P < 0.001). A pattern of dose effect was identified.
      For any event (osteoporosis/hip fracture/vertebral fracture), the aHR for PPI use
      of 1-90, 91-365, and > 365 cDDDs was 1.22 (P < 0.001), 1.27 (P < 0.001), and 1.66
      (P < 0.001), respectively. For each outcome, the highest dose was associated with
      the highest risk, with aHR of 1.79 (P < 0.001), 1.41 (P = 0.039), and 1.82 (P <
      0.001) for osteoporosis, hip fracture, and vertebral fracture, respectively. Age-
      and sex-stratified analyses revealed similar patterns. CONCLUSIONS: PPI use is
      associated with an increased risk of osteoporosis, hip fracture, and vertebral
      fracture in stroke patients.

PMID- 29032385
TI  - Exercise training response heterogeneity: physiological and molecular insights.
AB  - The overall beneficial effects of exercise are well studied, but why some people
      do not respond favourably to exercise is less understood. The National Institutes
      of Health Common Fund has recently launched the large-scale discovery project
      'Molecular Transducers of Physical Activity in Humans' to examine the
      physiological and molecular (i.e. genetic, epigenetic, lipidomic, metabolomic,
      proteomic, etc.) responses to exercise training. A nationwide, multicentre
      clinical trial such as this one also provides a unique opportunity to robustly
      investigate the non-response to exercise in thousands of individuals that have
      undergone supervised aerobic- and resistance-based exercise training
      interventions. The term 'non-responder' is used here to address the lack of a
      response (to an exercise intervention) in an outcome specified a priori.
      Cardiorespiratory fitness ([Formula: see text]) as an exercise response variable
      was recently reviewed; thus, this review focuses on metabolic aspects of the non
      response to exercise training. Integrated -omics platforms are discussed as an
      approach to disentangle the complicated relationships between endogenous and
      exogenous factors that drive the lack of a response to exercise in some
      individuals. Harnessing the power of combined -omics platforms with deep clinical
      phenotyping of human study participants will advance the field of exercise
      metabolism and shift the paradigm, allowing exercise interventions to be targeted
      at those most likely to benefit and identifying novel approaches to treat those
      who do not.

PMID- 29032386
TI  - Biomonitoring of Urban Pollution Using Silicon-Accumulating Species,
      Phyllostachys aureosulcata 'Aureocaulis'.
AB  - We investigated metal accumulation in bamboo leaves during three seasons at three
      urban locations differing in pollution levels. The higher content of Cu, Pb, and
      Zn in the leaves was in correlation with the highest bioavailable content of
      these elements in the soil at the most polluted location. The content of leaf
      trace elements was higher in summer and autumn compared to spring. Scanning
      electron microscopy with energy dispersive X-ray spectroscopy showed that Si
      accumulation in bamboo leaves was the highest in epidermis and vascular tissue,
      and was co-localized with trace metals. Analysis of phytoliths showed co
      deposition of Al, C, and Si, implying the involvement of Si in metal
      detoxification. Compared to a common urban tree, linden, bamboo showed better
      capacity to maintain cellular redox homeostasis under deteriorated environmental
      conditions. The results suggest that bamboo can be efficiently used for
      biomonitoring of air and soil metal pollution and remediation in urban areas.

PMID- 29032387
TI  - An Assessment of Heavy Metal Contamination on the Surface Sediment of Seagrass
      Beds at the Khanh Hoa Coast, Vietnam.
AB  - Seagrasses beds are vulnerable ecosystems. Human-induced disturbances, including
      heavy metal pollution, cause losses in seagrass beds. Assessment of the heavy
      metal concentration in seagrass meadows is an urgent need in order to protect and
      sustain these ecosystems. The concentration of eight trace metals in the surface
      sediment was observed from six seagrass beds at Khanh Hoa's coast, Vietnam. Three
      pollution indices and statistical analysis were used to evaluate the levels of
      contamination with these elements. This report on heavy metals within seagrass
      beds in Vietnam shows that, based on enrichment factors, only one location
      revealed moderately severe enrichment of Cu. Geo-accumulation indices fall in the
      uncontaminated class at all locations whereas for the ecological risk factor,
      values of Cu at My Giang and of Pb at Thuy Trieu were in a moderate risk class.
      Hence, two of eight locations may be exposed to high Cu and Pb.

PMID- 29032388
TI  - Ethanol metabolism varies with hypoxia tolerance in ten cyprinid species.
AB  - During periods of severe hypoxia or anoxia, Carassius spp. are known for their
      ability to produce ethanol as their anaerobic end product, which diffuses into
      the environment thereby reducing the osmotic and acidotic load associated with
      "anaerobic" glycolysis. However, the relationship between alcohol dehydrogenase
      (ADH) and acetaldehyde dehydrogenase (ALDH) activities, key ethanol metabolizing
      enzymes, and hypoxia tolerance among Carassius spp. and their closely related non
      ethanol-producing cyprinids remains unclear. To address this, we quantified the
      activity levels of key anaerobic enzymes in liver and muscle in species of
      cyprinids over 48 h of severe hypoxia exposure (0.7 kPa). As predicted, muscle
      ADH activity was highest in the two most hypoxia-tolerant species (Carassius
      spp.), with very low levels present in the other species examined. However, liver
      ADH activities showed an inverse relationship with hypoxia tolerance, with the
      most hypoxia-tolerant fish having the lowest ADH activity. There was no
      correlation between hypoxia tolerance and ALDH and LDH activities in muscle or
      liver. All species produced lactate, reaching their highest levels after 8 h, but
      returning to near-baseline levels by 48 h of sustained exposure to hypoxia,
      suggesting lactate oxidation or depressed ATP demand. Liver glycogen content was
      not affected by 48 h hypoxia exposure in the most hypoxia-tolerant species,
      whereas the least tolerant species consumed the majority of the liver glycogen
      stores, which is probably due to the greater relative hypoxia exposure
      experienced by these species. Our findings that liver ADH activities were
      inversely related to hypoxia tolerance suggests that in all but Carassius spp.,
      the ethanol metabolizing pathways in cyprinids is largely similar to that
      observed in other vertebrates and plays a role in the detoxification of ethanol.
      Furthermore, conservation of glycogen stores may be the result of metabolic
      depressing pathways in the more tolerant species, regardless of the ability to
      produce ethanol, or adaptations that improve oxygen uptake to reduce metabolic
      demands due to hypoxia.

PMID- 29032391
TI  - Representation of environmental shape in the hippocampus of domestic chicks
      (Gallus gallus).
AB  - The hippocampus plays an important role in spatial encoding and memory across
      various vertebrate species. In rodents, hippocampal neurons are particularly
      sensitive to a change in environmental geometry. Given the similarities in
      function between the mammalian and avian hippocampi, we aimed to measure whether
      enclosures varying in geometric shape (square and rectangle) can differentially
      activate hippocampal cells in the domestic chick (Gallus gallus domesticus).
      Chicks exposed to both a square and a rectangular arena exhibited a significantly
      higher neural activation (as measured by c-Fos expression) than those exposed
      twice to just the square or just the rectangle (both of which were significantly
      higher in activation than a one-environment control group). For the first time in
      an avian species, we show that exposure to two enclosures of different geometric
      shape activates the hippocampus to a greater degree, suggesting a possible effect
      of spatial remapping.

PMID- 29032389
TI  - Complementary and Integrative Medicine in Hematologic Malignancies: Questions and
      Challenges.
AB  - Hematologic malignancies represent 9.7% of all cancers, making them the fourth
      most common type of cancer in the United States. The aggressive and complex
      treatments administered in hematologic malignancies result in a high burden of
      psychological needs. Complementary and integrative medicine (CIM) is becoming one
      of the options that patients use to address their distress during and after
      cancer treatments. It is not clear whether appropriate CIM can relieve distress
      in patients affected by these malignancies. This review covers the potential
      benefits of CIM as relates to nutrition, nutritional supplements, exercise,
      circadian rhythm, methods for reducing distress during bone marrow aspiration,
      massage therapy, and acupuncture, in treating patients with hematological
      malignancies. This review may provide a framework to enhance patient-doctor
      dialogue regarding CIM use in hematologic malignancies.

PMID- 29032390
TI  - Psychosocial work environment and mental health-related long-term sickness
      absence among nurses.
AB  - PURPOSE: We investigated which job demands and job resources were predictive of
      mental health-related long-term sickness absence (LTSA) in nurses. METHODS: The
      data of 2059 nurses were obtained from the Norwegian survey of Shift work, Sleep
      and Health. Job demands (psychological demands, role conflict, and harassment at
      the workplace) and job resources (social support at work, role clarity, and fair
      leadership) were measured at baseline and linked to mental health-related LTSA
      during 2-year follow-up. Cox regression models estimated hazard ratios (HR) and
      related 95% confidence intervals (CI). The c-statistic was used to investigate
      the discriminative ability of the Cox regression models. RESULTS: A total of 1533
      (75%) nurses were included in the analyses; 103 (7%) of them had mental health
      related LTSA during 2-year follow-up. Harassment (HR = 1.07; 95% CI 1.01-1.17)
      and social support (HR = 0.92; 95% CI 0.87-0.98) were associated with mental
      health-related LTSA. However, the Cox regression model did not discriminate
      between nurses with and without mental health-related LTSA (c = 0.59; 95% CI 0.53
      0.65). CONCLUSIONS: Harassment was positively and social support at the workplace
      was negatively related to mental health-related LTSA, but both failed to
      discriminate between nurses with and without mental health-related LTSA during 2
      year follow-up.

PMID- 29032392
TI  - Exercise and gastrointestinal symptoms: running-induced changes in intestinal
      permeability and markers of gastrointestinal function in asymptomatic and
      symptomatic runners.
AB  - PURPOSE: Athletes frequently experience gastrointestinal (GI) symptoms during
      training and competition. Although the prevalence of exercise-induced GI symptoms
      is high, the mechanisms leading to GI distress during exercise are not fully
      understood. The aim of this study was to identify running-induced changes in
      intestinal permeability and markers of GI function and investigate their
      association with gastrointestinal symptoms. METHODS: We recruited 17 active
      runners who we allocated as either asymptomatic or symptomatic based on their
      history of experiencing GI symptoms during running. The participants took part in
      a running test where they were asked to run for 90 min at 80% of their best 10 km
      race speed. Intestinal permeability was measured at baseline and after the
      running test. Levels of serum intestinal fatty acid-binding protein (I-FABP),
      zonulin, bacterial lipopolysaccharide (LPS), and fecal calprotectin were also
      measured at baseline and after the running test. RESULTS: Running induced a
      significant increase in intestinal permeability and serum I-FABP concentration
      but there were no differences between asymptomatic and symptomatic runners. Serum
      LPS activity did not change from baseline following the running test but the
      symptomatic group exhibited higher LPS activity at baseline compared to the
      asymptomatic runners. CONCLUSIONS: Running for 90 min at a challenging pace
      causes small intestinal damage and increases intestinal permeability. However,
      these alterations in GI function do not appear to correlate with the development
      of GI symptoms during running.

PMID- 29032393
TI  - Acute effects of repeated cycling sprints in hypoxia induced by voluntary
      hypoventilation.
AB  - PURPOSE: This study aimed to investigate the acute responses to repeated-sprint
      exercise (RSE) in hypoxia induced by voluntary hypoventilation at low lung volume
      (VHL). METHODS: Nine well-trained subjects performed two sets of eight 6-s
      sprints on a cycle ergometer followed by 24 s of inactive recovery. RSE was
      randomly carried out either with normal breathing (RSN) or with VHL (RSH-VHL).
      Peak (PPO) and mean power output (MPO) of each sprint were measured. Arterial
      oxygen saturation, heart rate (HR), gas exchange and muscle concentrations of oxy
      ([O2Hb]) and deoxyhaemoglobin/myoglobin ([HHb]) were continuously recorded
      throughout exercise. Blood lactate concentration ([La]) was measured at the end
      of the first (S1) and second set (S2). RESULTS: There was no difference in PPO
      and MPO between conditions in all sprints. Arterial oxygen saturation (87.7 +/-
      3.6 vs 96.9 +/- 1.8% at the last sprint) and HR were lower in RSH-VHL than in RSN
      during most part of exercise. The changes in [O2Hb] and [HHb] were greater in RSH
      VHL at S2. Oxygen uptake was significantly higher in RSH-VHL than in RSN during
      the recovery periods following sprints at S2 (3.02 +/- 0.4 vs 2.67 +/- 0.5 L min
      1 on average) whereas [La] was lower in RSH-VHL at the end of exercise (10.3 +/-
      2.9 vs 13.8 +/- 3.5 mmol.L-1; p < 0.01). CONCLUSIONS: This study shows that
      performing RSE with VHL led to larger arterial and muscle deoxygenation than with
      normal breathing while maintaining similar power output. This kind of exercise
      may be worth using for performing repeated sprint training in hypoxia.

PMID- 29032395
TI  - ptxD gene in combination with phosphite serves as a highly effective selection
      system to generate transgenic cotton (Gossypium hirsutum L.).
AB  - KEY MESSAGE: This report demonstrates the usefulness of ptxD/phosphite as a
      selection system that not only provides a highly efficient and simple means to
      generate transgenic cotton plants, but also helps address many of the concerns
      related to the use of antibiotic and herbicide resistance genes in the production
      of transgenic crops. Two of the most popular dominant selectable marker systems
      for plant transformation are based on either antibiotic or herbicide resistance
      genes. Due to concerns regarding their safety and in order to stack multiple
      traits in a single plant, there is a need for alternative selectable marker
      genes. The ptxD gene, derived from Pseudomonas stutzeri WM88, that confers to
      cells the ability to convert phosphite (Phi) into orthophosphate (Pi) offers an
      alternative selectable marker gene as demonstrated for tobacco and maize. Here,
      we show that the ptxD gene in combination with a protocol based on selection
      medium containing Phi, as the sole source of phosphorus (P), can serve as an
      effective and efficient system to select for transformed cells and generate
      transgenic cotton plants. Fluorescence microscopy examination of the cultures
      under selection and molecular analyses on the regenerated plants demonstrate the
      efficacy of the system in recovering cotton transformants following Agrobacterium
      mediated transformation. Under the ptxD/Phi selection, an average of 3.43
      transgenic events per 100 infected explants were recovered as opposed to only
      0.41% recovery when bar/phosphinothricin (PPT) selection was used. The event
      recovery rates for nptII/kanamycin and hpt/hygromycin systems were 2.88 and
      2.47%, respectively. Molecular analysis on regenerated events showed a selection
      efficiency of ~ 97% under the ptxD/Phi system. Thus, ptxD/Phi has proven to be a
      very efficient, positive selection system for the generation of transgenic cotton
      plants with equal or higher transformation efficiencies compared to the commonly
      used, negative selection systems.

PMID- 29032397
TI  - Correction to: Extent and Location of the Excitatory and Inhibitory Cortical Hand
      Representation Maps: A Navigated Transcranial Magnetic Stimulation Study.
AB  - The original version of this article unfortunately contained an error. An error
      in the transformation between coordinate systems used to derive part of the
      results has been noticed.

PMID- 29032394
TI  - Clinical performance of 68Ga-PSMA-11 PET/MRI for the detection of recurrent
      prostate cancer following radical prostatectomy.
AB  - PURPOSE: Sensitive visualization of recurrent prostate cancer foci is a challenge
      in patients with early biochemical recurrence (EBR). The recently established
      68Ga-PSMA-11 PET/CT has significantly improved the detection rate with published
      values of up to 55% for patients with a serum PSA concentration between 0.2-0.5
      ng/mL. The increased soft tissue contrast in the pelvis using simultaneous 68Ga
      PSMA-11 PET/MRI might further improve the detection rate in patients with EBR and
      low PSA values over PET/CT. METHODS: We retrospectively analyzed a cohort of 56
      consecutive patients who underwent a 68Ga-PSMA-11 PET/MRI for biochemical
      recurrence in our institution between April and December 2016 with three readers.
      Median PSA level was 0.99 ng/mL (interquartile range: 3.1 ng/mL). Detection of
      PSMA-positive lesions within the prostate fossa, local and distant lymph nodes,
      bones, or visceral organs was recorded. Agreement among observers was evaluated
      with Fleiss's kappa (k). RESULTS: Overall, in 44 of 56 patients (78.6%) PSMA
      positive lesions were detected. In four of nine patients (44.4%) with a PSA < 0.2
      ng/mL, suspicious lesions were detected (two pelvic and one paraaortic lymph
      nodes, and two bone metastases). In eight of 11 patients (72.7%) with a PSA
      between 0.2 and < 0.5 ng/mL, suspicious lesions were detected (two local
      recurrences, six lymph nodes, and one bone metastasis). Five out of 20 patients
      with a PSA < 0.5 ng/mL had extrapelvic disease. In 12 of 15 patients (80.0%) with
      a PSA between 0.5 and < 2.0 ng/mL, suspicious lesions were detected (four local
      recurrences, nine lymph nodes, and four bone metastases). In 20 of 21 patients
      (95.2%) with a PSA >2.0 ng/mL, suspicious lesions were detected. The overall
      interreader agreement for cancer detection was excellent (kappa = 0.796, CI 0.645
      0.947). CONCLUSIONS: Our data show that 68Ga-PSMA-11 PET/MRI has a high detection
      rate for recurrent prostate cancer even at very low PSA levels <0.5 ng/mL.
      Furthermore, even at those low levels extrapelvic disease can be localized in 25%
      of the cases and local recurrence alone is seen only in 10%.

PMID- 29032396
TI  - Assessing Adherence to Antihypertensive Therapy in Primary Health Care in
      Namibia: Findings and Implications.
AB  - INTRODUCTION: Namibia has the highest burden and incidence of hypertension in sub
      Sahara Africa. Though non-adherence to antihypertensive therapy is an important
      cardiovascular risk factor, little is known about potential ways to improve
      adherence in Namibia following universal access. The objective of this study is
      to validate the Hill-Bone compliance scale and determine the level and predictors
      of adherence to antihypertensive treatment in primary health care settings in sub
      urban townships of Windhoek, Namibia. METHODS: Reliability was determined by
      Cronbach's alpha. Principal component analysis (PCA) was used to assess construct
      validity. RESULTS: The PCA was consistent with the three constructs for 12 items,
      explaining 24.1, 16.7 and 10.8% of the variance. Cronbach's alpha was 0.695. None
      of the 120 patients had perfect adherence to antihypertensive therapy, and less
      than half had acceptable levels of adherence (>= 80%). The mean adherence level
      was 76.7 +/- 8.1%. Three quarters of patients ever missed their scheduled clinic
      appointment. Having a family support system (OR = 5.4, 95% CI 1.687-27.6, p =
      0.045) and attendance of follow-up visits (OR = 3.1, 95% CI 1.1-8.7, p = 0.03)
      were significant predictors of adherence. Having HIV/AIDs did not lower
      adherence. CONCLUSIONS: The modified Namibian version of the Hill-Bone scale is
      reliable and valid for assessing adherence to antihypertensives in Namibia. There
      is sub-optimal adherence to antihypertensive therapy among primary health cares
      in Namibia. This needs standardized systems to strengthen adherence monitoring as
      well as investigation of other factors including transport to take full advantage
      of universal access.

PMID- 29032398
TI  - Analysis of miR-96 and miR-133a Expression in Gastrointestinal Neuroendocrine
      Neoplasms.
AB  - Grading of gastrointestinal neuroendocrine neoplasms (GI-NENs) relies mainly on
      mitotic activity and Ki-67 proliferation index. It is often difficult to predict
      metastatic potential of these neoplasms. Recent studies have shown that GI-NENs
      express a wide spectrum of microRNAs. We examined two microRNAs (miR-96 and miR
      133a) that were recently identified in GI-NENs to determine if they could assist
      in evaluating the biological behavior of these neoplasms. A tissue microarray
      (TMA) was constructed with 51 primary GI-NENs, mainly from the small intestine
      and metastatic tumors from the same cases, including liver metastases (N = 20)
      and lymph node metastases (N = 33). The cases were immunohistochemically stained
      for chromogranin A, synaptophysin, and Ki-67. In situ hybridization (ISH) was
      done with probes from Exiqon (Woburn, MA). Quantitative RT-PCR (qRT-PCR) was also
      performed on all the cases (N = 105). ISH analysis showed that miR-96 expression
      was significantly higher in the liver metastatic neoplasms compared to the
      primary NENs (p < 0.05); however, it was not significant for miR-133a expression
      levels. qRT-PCR showed that miR-96 levels were increased during progression from
      the primary tumors to metastases in the liver. qRT-PCR showed a decrease in miR
      133a in the liver metastases compared to the primary tumors (p < 0.05).
      Appendiceal carcinoids without metastases (n = 3) had low levels of miR-96 and
      high levels of miR-133a by qPCR. The study suggests that analysis of these two
      microRNAs by qRT-PCR may be useful in detecting more aggressive GI-NENs and that
      ISH analysis may also assist in the evaluation of patients with GI-NENs.

PMID- 29032399
TI  - Evidence of Extracellular Vesicles Biogenesis and Release in Mouse Embryonic Stem
      Cells.
AB  - Extracellular vesicles (EVs) released by mouse embryonic stem cells (mESCs) are
      considered a source of bioactive molecules that modulate their microenvironment
      by acting on intercellular communication. Either intracellular endosomal
      machinery or their derived EVs have been considered a relevant system of signal
      circuits processing. Herein, we show that these features are found in mESCs.
      Ultrastructural analysis revealed structures and organelles of the endosomal
      system such as coated pits and endocytosis-related vesicles, prominent rough
      endoplasmic reticulum and Golgi apparatus, and multivesicular bodies (MVBs)
      containing either few or many intraluminal vesicles (ILVs) that could be released
      as exosomes to extracellular milieu. Besides, budding vesicles shed from the
      plasma membrane to the extracellular space is suggestive of microvesicle
      biogenesis in mESCs. mESCs and mouse blastocyst express specific markers of the
      Endosomal Sorting Complex Required for Transport (ESCRT) system. Ultrastructural
      analysis and Nanoparticle Tracking Analysis (NTA) of isolated EVs revealed a
      heterogeneous population of exosomes and microvesicles released by mESCs. These
      vesicles contain Wnt10b and the Notch ligand Delta-like 4 (DLL4) and also the co
      chaperone stress inducible protein 1 (STI1) and its partner Hsp90. Wnt10b and
      Dll4 colocalize with EVs biogenesis markers in mESCs. Overall, the present study
      supports the function of the mESCs endocytic network and their EVs as players in
      stem cell biology.

PMID- 29032400
TI  - Fine mapping of QTL qCTB10-2 that confers cold tolerance at the booting stage in
      rice.
AB  - KEY MESSAGE: The QTL qCTB10 - 2 controlling cold tolerance at the booting stage
      in rice was delimited to a 132.5 kb region containing 17 candidate genes and 4
      genes were cold-inducible. Low temperature at the booting stage is a major
      abiotic stress-limiting rice production. Although some QTL for cold tolerance in
      rice have been reported, fine mapping of those QTL effective at the booting stage
      is few. Here, the near-isogenic line ZL31-2, selected from a BC7F2 population
      derived from a cross between cold-tolerant variety Kunmingxiaobaigu (KMXBG) and
      the cold-sensitive variety Towada, was used to map a QTL on chromosome 10 for
      cold tolerance at the booting stage. Using BC7F3 and BC7F4 populations, we
      firstly confirmed qCTB10-2 and gained confidence that it could be fine mapped.
      QTL qCTB10-2 explained 13.9 and 15.9% of the phenotypic variances in those two
      generations, respectively. Using homozygous recombinants screened from larger
      BC7F4 and BC7F5 populations, qCTB10-2 was delimited to a 132.5 kb region between
      markers RM25121 and MM0568. 17 putative predicted genes were located in the
      region and only 5 were predicted to encode expressed proteins. Expression
      patterns of these five genes demonstrated that, except for constant expression of
      LOC_Os10g11820, LOC_Os10g11730, LOC_Os10g11770, and LOC_Os10g11810 were highly
      induced by cold stress in ZL31-2 compared to Towada, while LOC_Os10g11750 showed
      little difference. Our results provide a basis for identifying the genes
      underlying qCTB10-2 and indicate that markers linked to the qCTB10-2 locus can be
      used to improve the cold tolerance of rice at the booting stage by marker
      assisted selection.

PMID- 29032401
TI  - Fine mapping of the genic male-sterile ms 1 gene in Capsicum annuum L.
AB  - KEY MESSAGE: The genomic region cosegregating with the genic male-sterile ms 1
      gene of Capsicum annuum L. was delimited to a region of 869.9 kb on chromosome 5
      through fine mapping analysis. A strong candidate gene, CA05g06780, a homolog of
      the Arabidopsis MALE STERILITY 1 gene that controls pollen development, was
      identified in this region. Genic male sterility caused by the ms 1 gene has been
      used for the economically efficient production of massive hybrid seeds in paprika
      (Capsicum annuum L.), a colored bell-type sweet pepper. Previously, a CAPS
      marker, PmsM1-CAPS, located about 2-3 cM from the ms 1 locus, was reported. In
      this study, we constructed a fine map near the ms 1 locus using high-resolution
      melting (HRM) markers in an F2 population consisting of 1118 individual plants,
      which segregated into 867 male-fertile and 251 male-sterile plants. A total of 12
      HRM markers linked to the ms 1 locus were developed from 53 primer sets targeting
      intraspecific SNPs derived by comparing genome-wide sequences obtained by next
      generation resequencing analysis. Using this approach, we narrowed down the
      region cosegregating with the ms 1 gene to 869.9 kb of sequence. Gene prediction
      analysis revealed 11 open reading frames in this region. A strong candidate gene,
      CA05g06780, was identified; this gene is a homolog of the Arabidopsis MALE
      STERILITY 1 (MS1) gene, which encodes a PHD-type transcription factor that
      regulates pollen and tapetum development. Sequence comparison analysis suggested
      that the CA05g06780 gene is the strongest candidate for the ms 1 gene of paprika.
      To summarize, we developed a cosegregated marker, 32187928-HRM, for marker
      assisted selection and identified a strong candidate for the ms 1 gene.

PMID- 29032402
TI  - Interaction between chlorhexidine and fluoride in a mouthrinse solution-a 4-day
      and 6-week randomized clinical pilot study.
AB  - OBJECTIVE: The aim of the present investigation was to study if there is a
      reduced clinical effect and fluoride retention of a mouthrinse solution
      containing both chlorhexidine (CHX) and sodium fluoride (NaF). MATERIAL AND
      METHODS: Two clinical trials were designed as double-blind, randomized, cross
      over studies. In study I, 16 healthy subjects were asked to rinse twice daily for
      1 min during 4 days of no tooth brushing with four solutions: (1) 0.12% CHX +
      0.2% NaF, (2) 0.2% NaF, (3) 0.12% CHX, and (4) placebo. In study II, another 16
      healthy subjects rinsed with the same four solutions twice daily after tooth
      brushing during a 6-week period. Plaque formation, gingivitis, and
      microbiological samples from plaque and saliva, as well as fluoride retention,
      were analyzed. RESULTS: Both studies showed that both CHX + NaF and CHX
      mouthrinses had the same clinical effect with regards to plaque formation and
      microflora in plaque and saliva. Similarly, fluoride retention was not altered by
      the CHX + NaF mouthrinse compared to the NaF solution. CONCLUSION: The
      combination of CHX and NaF in a mouthrinse showed the same clinical effect as the
      CHX solution. The retention of fluoride in the oral cavity was not affected by
      the combination of NaF and CHX. CLINICAL RELEVANCE: A mouthrinse solution
      containing a mixture of CHX and NaF may be an interesting product for risk
      patients for caries and periodontal disease. However, this should be verified in
      further long-term clinical studies.

PMID- 29032403
TI  - Mate tea (Ilex paraguariensis) improves bone formation in the alveolar socket
      healing after tooth extraction in rats.
AB  - OBJECTIVES: The objective of this study was to investigate the effects of mate
      tea (MT) [Ilex paraguariensis] on alveolar socket healing after tooth extraction.
      MATERIALS AND METHODS: Sixteen male rats were divided into MT and control groups.
      MT was administered by intragastric gavage at a dose of 20 mg/kg/day for 28 days
      before and 28 days after right maxillary incisor extraction. The control group
      received an equal volume of water. Histopathological and histometric analysis of
      the neoformed bone area and osteocyte density were performed, as well as
      immunohistochemical analysis of osteocalcin (OCN), receptor activator of nuclear
      factor kappa-B ligand (RANKL), osteoprotegerin (OPG), tartrate-resistant acid
      phosphatase (TRAP), and manganese superoxide dismutase (MnSOD) in the alveolar
      socket. Calcium, phosphorus, alkaline phosphatase (ALP) activity, total
      antioxidant capacity (TAC), and malondialdehyde (MDA) were measured in plasma,
      whereas TRAP activity was determined in serum. RESULTS: Histometry evidenced an
      increase in bone area (P < 0.0001) and osteocyte density (P < 0.0001). MT
      increased immunolabeling of MnSOD (P < 0.001), OCN (P < 0.0001), RANKL (P <
      0.001), OPG (P < 0.0001), and TRAP (P < 0.001). Calcium and phosphorus
      concentrations did not differ between the groups. In addition, MT enhanced ALP (P
      < 0.05) and TRAP (P < 0.0001) activities. MT increased the TAC (P < 0.001),
      whereas it reduced MDA concentrations (P < 0.0001). CONCLUSIONS: MT increases
      bone area and osteocyte density in the alveolar socket healing on day 28 after
      tooth extraction. CLINICAL RELEVANCE: Regular MT ingestion improves the
      antioxidant defenses and bone formation, which is beneficial for alveolar socket
      bone healing after tooth extraction.

PMID- 29032404
TI  - Dietary Supplementation with Methylseleninic Acid Inhibits Mammary Tumorigenesis
      and Metastasis in Male MMTV-PyMT Mice.
AB  - Male breast cancer, which makes up approximately 1% of all breast cancers, is an
      aggressive disease with poor prognosis. We investigated the effects of dietary
      supplementation with selenium in the form of methylseleninic acid [(MSeA) 2.5 mg
      selenium/kg] on mammary tumorigenesis in male MMTV-PyMT mice. The mammary tumor
      latency was 14.6 weeks for the MSeA-fed group and 13.8 weeks for the controls fed
      the AIN93G diet (p < 0.05). Dietary supplementation with MSeA, versus the
      control, resulted in a 72% reduction in tumor progression, a 46% reduction in
      both final volume and weight of mammary tumors, and a 70% reduction in the number
      of lung metastases. Mammary tumorigenesis in MMTV-PyMT mice, versus non-tumor
      bearing wild-type mice, resulted in significant increases in concentrations of
      plasminogen activator inhibitor-1, urokinase plasminogen activator, monocyte
      chemotactic protein-1, and vascular endothelial growth factor, but not aromatase
      and estrogen, in the plasma. Concentrations of all variables mentioned above in
      both plasma and mammary tumors were lower in MSeA-fed mice. Mammary tumorigenesis
      reduced plasma levels of adiponectin compared to non-tumor-bearing controls.
      Adiponectin concentrations in mammary tumors, but not in plasma, were higher in
      MSeA-fed mice than in controls. In summary, dietary supplementation with selenium
      in the form of MSeA inhibits mammary tumorigenesis and its pulmonary metastasis
      in male MMTV-PyMT mice.

PMID- 29032405
TI  - Agaricus blazei Murill Polysaccharides Protect Against Cadmium-Induced Oxidative
      Stress and Inflammatory Damage in Chicken Spleens.
AB  - Agaricus blazei Murill polysaccharide (ABP) has exhibited antioxidant and
      immunoregulatory activity. The aim of this study was to investigate the effect of
      ABP on cadmium (Cd)-induced antioxidant functions and inflammatory damage in
      chicken spleens. In this study, groups of 7-day-old chickens were fed with normal
      saline (0.2 mL single/day), CdCl2 (140 mg/kg/day), ABP (30 mg/mL, 0.2 mL
      single/day), and Cd + ABP (140 mg/kg/day + 0.2 mL ABP). Spleens were separated on
      the 20th, 40th, and 60th day for each group. The Cd contents, expression of
      melanoma-associated differentiation gene 5 (MDA5) and its downstream signaling
      molecules (interferon promoter-stimulating factor 1 (IPS-1), transcription
      factors interferon regulatory factor 3 (IRF3), and nuclear factor kappa-light
      chain-enhancer of activated B cells (NF-kappaB)), the content of cytokines
      (interleukin 1beta (IL-1beta), interleukin 6 (IL-6), tumor necrosis factor-alpha
      (TNF-alpha) and beta interferon (IFN-beta)), protein levels of heat shock
      proteins (HSPs), levels of malondialdehyde (MDA), activities of glutathione
      peroxidase (GSH-Px) and superoxide dismutase (SOD), and histopathological changes
      of spleens were detected on the 20th, 40th, and 60th day. The results showed that
      ABP significantly reduced the accumulation of Cd in the chicken spleens and
      reduced the expression of MDA5, IPS-1, IRF-3, and NF-kappaB; their downstream
      inflammatory cytokines, IL-1beta, IL-6, TNF-alpha, and IFN-beta; and the protein
      levels of HSPs (HSP60, HSP70, and HSP90) in spleens. The activities of
      antioxidant enzymes (SOD and GSH-Px) significantly increased, and the level of
      MDA decreased in the ABP + Cd group. The results indicate that ABP has a
      protective effect on Cd-induced damage in chicken spleens.

PMID- 29032406
TI  - Lactobacillus gasseri attenuates allergic airway inflammation through PPARgamma
      activation in dendritic cells.
AB  - : Lactobacilli prevent the early development of allergic diseases in children and
      experimental asthma in mice. However, the detailed mechanism underlying this
      action remains unknown. We aimed to explore the activation pathway in the host by
      Lactobacillus and identify its immunomodulation mechanism in allergic asthma.
      Continuous administration of 107 cfu, but not 109 cfu, of L. gasseri for 4 weeks
      prevented Dermatophagoides pteronyssinus (Der p)-induced airway hypersensitivity
      and inflammation in a mouse model of allergic asthma. DNA microarray analysis of
      the mesenteric and lung draining lymph nodes revealed a significant decrease in
      inflammatory chemokines and increase in gene expression in carbohydrate and lipid
      metabolism, particularly of PPARgamma, in 107 cfu L. gasseri-administered mice
      compared with untreated mice. Compared with WT mice, Der p-sensitized
      PPARgammaL/+ mice showed increased airway hyperresponsiveness to methacholine,
      inflammatory cell infiltration, and inflammatory cytokine secretion in
      bronchoalveolar fluid. Moreover, the protective effects of L. gasseri were lost
      in Der p-induced airway inflammation in PPARgammaL/+ mice, and L. gasseri-induced
      PPARgamma activation in BMDCs inhibited the development of allergic airway
      inflammation in both PPARgamma WT and PPARgammaL/+ mice. L. gasseri may act via a
      novel PPARgamma activation pathway in DCs to alleviate allergen-induced airway
      inflammation in allergic asthma. KEY MESSAGES: L. gasseri prevents mite allergen
      (Der p)-induced airway inflammation. Prevention of airway inflammation occurs via
      activation of PPARgamma in dendritic cells. L. gasseri administration does not
      reverse Der p-induced airway inflammation in PPARgamma(+/-) mice. L. gasseri
      induced PPARgamma activation inhibits development of airway inflammation in WT
      and PPARgamma(+/-) mice.

PMID- 29032408
TI  - The natural history of depressive symptoms in patients with incident Parkinson's
      disease: a prospective cohort study.
AB  - Depression is common in patients with Parkinson disease and causes suffering and
      increased caregiver burden. A better understanding of depressive symptoms in
      Parkinson disease, their progression, and risk factors may, therefore, benefit
      management of these patients. The present study included 187 drug-naive patients
      with incident PD and 166 controls from the population-based Norwegian ParkWest
      project. Depressive symptoms were examined with the Montgomery and Aasberg
      Depression Rating Scale (MADRS) at time of diagnosis and inclusion in the study
      and after 1, 3, 5, and 7 years of follow-up. Associations between MADRS scores
      and risk factors were assessed using generalized estimating equations (GEE). The
      mean MADRS score from all 823 examinations during the study period was 4.2 in
      patients and 1.3 in 732 examinations among controls. Among controls, the
      occurrence of depressive symptoms was also lower and rather stable during follow
      up, while in patients, we observed a decrease from time of diagnosis and until
      the 1-year visit, followed by a steady increase in these symptoms over time.
      Factors associated with higher MADRS score in the multivariable model were female
      sex, being dependent, higher pain score, higher Unified PD Rating Scale (UPDRS)
      motor score, and lower Mini-Mental State Examination (MMSE) score. The results
      from this study underscore the importance and frequency of depressive symptoms in
      patients with early PD. Furthermore, risk factors that may be considered PD
      nonspecific are associated with depressive symptoms as are factors that reflect
      the progression of PD.

PMID- 29032407
TI  - Advances in understanding nociception and neuropathic pain.
AB  - Pain results from the activation of a subset of sensory neurones termed
      nociceptors and has evolved as a "detect and protect" mechanism. However, lesion
      or disease in the sensory system can result in neuropathic pain, which serves no
      protective function. Understanding how the sensory nervous system works and what
      changes occur in neuropathic pain are vital in identifying new therapeutic
      targets and developing novel analgesics. In recent years, technologies such as
      optogenetics and RNA-sequencing have been developed, which alongside the more
      traditional use of animal neuropathic pain models and insights from genetic
      variations in humans have enabled significant advances to be made in the
      mechanistic understanding of neuropathic pain.

PMID- 29032409
TI  - Agrobacterium-mediated floral dip transformation of the model polyploid species
      Arabidopsis kamchatica.
AB  - Polyploidization has played an important role in the speciation and
      diversification of plant species. However, genetic analyses of polyploids are
      challenging because the vast majority of the model species are diploids. The
      allotetraploid Arabidopsis kamchatica, which originated through the hybridization
      of the diploid Arabidopsis halleri and Arabidopsis lyrata, is an emerging model
      system for studying various aspects of polyploidy. However, a transgenic method
      that allows the insertion of a gene of interest into A. kamchatica is still
      lacking. In this study, we investigated the early development of pistils in A.
      kamchatica and confirmed the formation of open pistils in young flower buds
      (stages 8-9), which is important for allowing Agrobacterium to access female
      reproductive tissues. We established a simple Agrobacterium-mediated floral dip
      transformation method to transform a gene of interest into A. kamchatica by
      dipping A. kamchatica inflorescences bearing many young flower buds into a 5%
      sucrose solution containing 0.05% Silwet L-77 and Agrobacterium harboring the
      gene of interest. We showed that a screenable marker comprising fluorescence
      accumulating seed technology with green fluorescent protein was useful for
      screening the transgenic seeds of two accessions of A. kamchatica subsp.
      kamchatica and an accession of A. kamchatica subsp. kawasakiana.

PMID- 29032410
TI  - Relationship Between Circulating Fatty Acids and Fatty Acid Ethanolamide Levels
      After a Single 2-h Dietary Fat Feeding in Male Sprague-Dawley Rats : Elevated
      levels of oleoylethanolamide, palmitoylethanolamide, linoleoylethanolamide,
      arachidonoylethanolamide and docosahexanoylethanolamide after a single 2 h
      dietary fat feeding in male Sprague Dawley rats.
AB  - Previous studies show that long term variations in dietary fat consumption impact
      circulating fatty acid ethanolamide (FAE) concentrations, however, few studies
      have investigated short term effects of dietary fat feeding on FAE levels. The
      trial's objective was to explore the effect of acute feeding of varying amounts
      of dietary n-9 and n-3 fatty acids on plasma and organ levels of FAE. Sixty-four
      rats were assigned to four groups fed meals containing 40% of energy as either
      safflower oil (control), canola oil (CO), or DHA rich oil (DRO), each consumed as
      a bolus within a 2-h window. Plasma and tissue FAE levels were measured at 3, 6,
      12 and 24 h following the bolus. FAE profiles over time exhibited patterns that
      were specific both to FAE and to dietary fat type provided. At 3 h, plasma and
      liver OEA levels were higher (p < 0.05) in the 95% CO:5% DRO compared with other
      groups. At 12 h, plasma PEA levels were lower (p < 0.05) in the 50% CO:50% DRO
      group compared to the 95% CO group. Plasma DEA levels showed an increase (p <
      0.05) only after 24 h of feeding. All four dietary groups manifested increased
      DEA levels in a dose-dependent manner. Data demonstrate that a single meal
      feeding of diets with different ratios of fat types impacts tissue levels of FAE
      within a short time frame, which could further influence the physiological roles
      of FAE on appetite regulation and energy expenditure.

PMID- 29032412
TI  - Prognostication and Initiation of Therapy in Polycythemia Vera: Do We Have it
      Right?
AB  - ?.

PMID- 29032411
TI  - HIV Prevalence and Risk Behaviors in Male to Female (MTF) Transgender Persons in
      Tijuana, Mexico.
AB  - Compared to HIV research on men who have sex with men, less is known about the
      risks and vulnerabilities for HIV among Male to Female (MTF) transgender persons,
      particularly in different geographic regions like Mexico. In Tijuana, Mexico, a
      border city experiencing a dynamic HIV epidemic, no precedent data exists on the
      MTF transgender population. Our aims were to estimate HIV prevalence and examine
      the behaviors and characteristics of the population. We conducted a cross
      sectional study of 100 MTF transgender persons recruited through time location
      sampling in 2012. Participants underwent interviewer-administered (paper and pen)
      surveys and rapid tests for HIV. Descriptive univariate analyses were conducted
      on various factors, including sociodemographics, substance use, accessing social
      services (requested vs. received), stigma, and sex behaviors. A total of 22%
      tested positive for HIV, a prevalence higher than other key populations at risk
      for HIV in Tijuana.

PMID- 29032413
TI  - Choriocapillaris layer imaging with swept-source optical coherence tomography
      angiography in lamellar and full-thickness macular hole.
AB  - PURPOSE: To present characteristics of choriocapillaris layer imaging with swept
      source optical coherence tomography angiography (SS-OCTA) in eyes with macular
      hole (MH). METHODS: Patients with MH were included. Vascular density of
      choriocapillaris (VDC) and central flow void areas were obtained using SS-OCTA.
      Data were compared with age- and gender-matched normal controls. RESULTS: Fifty
      one patients with MH and 51 controls were included. Among the 51 patients with
      MH, 19 had lamellar MH (LMH) and 32 had full-thickness MH (FTMH). While VDC in
      LMH (79.26 +/- 4.06%) was not significantly different from that seen in fellow
      eyes (79.88 +/- 4.28%, P = 0.729) and normal controls (80.53 +/- 4.21%, P =
      1.000), VDC in surgically closed FTMH (74.60 +/- 7.37%) was similar to that of
      fellow eyes (75.45 +/- 7.39%, P = 0.400) but lower than that of controls (78.37
      +/- 7.13%, P = 0.011). On univariate analysis of 32 patients with unilateral
      sealed FTMH, VDC was not correlated with basal hole area (P = 0.797) or
      preoperative area of disrupted ellipsoid zone (P = 0.863). Central flow void was
      detected in 32 eyes. Mean central flow void area was 0.82 +/- 0.84 mm2, which
      correlated with preoperative area of disrupted ellipsoid zone (P = 0.001).
      CONCLUSIONS: Choriocapillaris layer imaging using SS-OCTA showed that
      choriocapillaris in both eyes of patients with unilateral FTMH had different
      characteristics from eyes with LMH or normal controls. These results suggest that
      variation in choriocapillaris layer flow is involved in the pathogenesis of MH.

PMID- 29032414
TI  - Influence of LASEK on Schiotz, Goldmann and dynamic contour Tonometry.
AB  - PURPOSE: Our purpose was to assess the effect of LASEK surgery on ocular rigidity
      and to compare its effect on intraocular pressure (IOP) readings with Goldmann
      applanation tonometry (GAT), Schiotz indentation tonometry (ST) and dynamic
      contour tonometry (DCT). METHODS: Prospective, observational, single-masked
      cohort study. One eye per patient from 31 consecutive subjects who underwent
      LASEK refractive surgery to correct myopia, as well as from 108 non-operated
      myopic patients, were included. IOP was measured using GAT, DCT, and ST. The
      coefficient of ocular rigidity (Ko) was obtained from the regression line of the
      three readings obtained with each weight of the ST. Linear multiple regression
      analysis was performed with dummy variables to assess the effect of age, central
      corneal thickness (CCT), and previous refractive surgery on IOP values. RESULTS:
      Age, CCT, and LASEK surgery explained 23% of the IOP readings with GAT, 11% with
      DCT, and had no significant influence on ST readings. The IOP readings obtained
      with GAT and DCT, but not with ST, were significantly different between LASEK and
      control groups. Significant differences in Ko were observed between LASEK (0.014
      mmHg/MUL +/-0.007) and control groups (0.021 mmHg/MUL +/-0.013) (P = 0.001). Ko
      values were not related with age or CCT, in either LASEK or control groups.
      CONCLUSIONS: ST readings seems to be less affected by LASEK surgery than the
      other tonometers evaluated. There is a difference in the ocular rigidity between
      the control and the LASEK eyes that it is not correlated with CCT, so it seems
      that ST can detect changes in the biomechanical behavior of the LASEK operated
      corneas.

PMID- 29032415
TI  - From aggregation to interpretation: how assessors judge complex data in a
      competency-based portfolio.
AB  - While portfolios are increasingly used to assess competence, the validity of such
      portfolio-based assessments has hitherto remained unconfirmed. The purpose of the
      present research is therefore to further our understanding of how assessors form
      judgments when interpreting the complex data included in a competency-based
      portfolio. Eighteen assessors appraised one of three competency-based mock
      portfolios while thinking aloud, before taking part in semi-structured
      interviews. A thematic analysis of the think-aloud protocols and interviews
      revealed that assessors reached judgments through a 3-phase cyclical cognitive
      process of acquiring, organizing, and integrating evidence. Upon conclusion of
      the first cycle, assessors reviewed the remaining portfolio evidence to look for
      confirming or disconfirming evidence. Assessors were inclined to stick to their
      initial judgments even when confronted with seemingly disconfirming evidence.
      Although assessors reached similar final (pass-fail) judgments of students'
      professional competence, they differed in their information-processing approaches
      and the reasoning behind their judgments. Differences sprung from assessors'
      divergent assessment beliefs, performance theories, and inferences about the
      student. Assessment beliefs refer to assessors' opinions about what kind of
      evidence gives the most valuable and trustworthy information about the student's
      competence, whereas assessors' performance theories concern their
      conceptualizations of what constitutes professional competence and competent
      performance. Even when using the same pieces of information, assessors
      furthermore differed with respect to inferences about the student as a person as
      well as a (future) professional. Our findings support the notion that assessors'
      reasoning in judgment and decision-making varies and is guided by their mental
      models of performance assessment, potentially impacting feedback and the
      credibility of decisions. Our findings also lend further credence to the
      assertion that portfolios should be judged by multiple assessors who should,
      moreover, thoroughly substantiate their judgments. Finally, it is suggested that
      portfolios be designed in such a way that they facilitate the selection of and
      navigation through the portfolio evidence.

PMID- 29032416
TI  - Non-attendance of vulnerable populations within epilepsy outpatient services in
      Ireland.
AB  - BACKGROUND: Outpatient non-attendance is a prevalent issue that contributes to
      significant wasted clinical resources and can be influenced by a number of
      complex factors. AIMS: The aim of this study is to characterize "did not attend"
      (DNA) rates in three identified subpopulations of epilepsy patients to determine
      if current care provision models suffice. METHODS: In this study, we identified
      all patients residing in social housing, in residential care, and those
      incarcerated who have been offered appointments by our service. We calculated the
      total number of appointments issued to each group over their entire interaction
      with our service and their subsequent non-attendance rate as a group.
      Additionally, we calculated the baseline DNA rate for our epilepsy clinic as a
      whole for comparison. RESULTS: We found that the baseline DNA rate for the clinic
      as a whole was 18.9%. Those in social housing, in residential care, and
      incarcerated had significantly higher DNA rates of 24, 20.2, and 54.3%,
      respectively. CONCLUSIONS: This study provided evidence that in certain groups of
      patients, clinicians may need to explore other care delivery models due to high
      DNA rates.

PMID- 29032417
TI  - Clinical evaluation for sublingual immunotherapy with Dermatophagoides farinae
      drops in adult patients with allergic asthma.
AB  - PURPOSE: The efficacy and safety of sublingual immunotherapy (SLIT) in house dust
      mite-induced allergic asthma (AA) have yet to be firmly established, especially
      in adult patients. Our objective is to evaluate the efficacy of SLIT with
      Dermatophagoides farinae drops in adult patients with AA. METHODS: One hundred
      and thirty-four adult patient data with house dust mite (HDM)-induced AA who had
      been treated for 2 years were collected. These patient data that we collected
      were divided into the SLIT group (n = 85) and control group (n = 49). All
      patients were treated with low to moderate dose of inhaled glucocorticoid and
      long-acting beta2 agonists. Patients in the SLIT group were further treated with
      D. farinae drops. Clinical scores including the total asthma symptom score
      (TASS), total asthma medicine score (TAMS), asthma control test (ACT), and peak
      flow percentage (PEF%) were assessed before treatment and at yearly visits. The
      presence of adverse events (AEs) were recorded once a month. RESULTS: Before
      treatment, the PEF% in the SLIT group was significantly lower than that in the
      control group (p < 0.05). After 2 years, both treatments were effective in the
      clinical scores when compared with baseline values (all p < 0.001). Meanwhile,
      the SLIT group showed significantly lower TASS and TAMS (all p < 0.001) and
      higher ACT (p < 0.001) and PEF% (p < 0.05) when compared with the control group.
      No severe systemic AEs were reported. CONCLUSIONS: SLIT with D. farinae drops
      plus pharmacotherapy is more effective than routine drug treatment in adult
      patients with AA.

PMID- 29032418
TI  - Transoral robotic surgery for squamous cell carcinomas of the posterior
      pharyngeal wall.
AB  - Posterior pharyngeal wall squamous cell carcinomas (SCCs) are rare and have an
      associated poor prognosis. Progress in transoral resection techniques, in
      particular, transoral robotic surgery (TORS), have renewed the role of surgery in
      their treatment. This article presents the oncological and functional results
      obtained by the French Group of Head and Neck Robotic Surgery for TORS for
      posterior pharyngeal wall SCC-curative surgery. This retrospective, multicentre
      study presents data collected between September 2009 and November 2013 for
      patients treated with TORS for posterior pharyngeal wall SCCs. Analysis of
      patient characteristics, tumour and treatment details were completed. Kaplan
      Meier analysis was used to calculate overall survival rates and recurrence-free
      survival rates. Student's t test and Chi2 test were also calculated. 23 patients
      were included (mean age of 62 years). 12 patients had a prior HNSCC. Ten patients
      had pT1 cancers. The overall two-year survival rate was 59%, but 89% for pT1
      compared to 28% for pT2-T3 (p = 0.01). It was noted that TORS was simple to
      perform, but generated significant post-operative dysphagia. Two cases of
      spondylodiscitis were reported as specific post-operative complications of TORS.
      In conclusion, TORS is a treatment solution for selected posterior pharyngeal
      wall SCCs. It provides a possible alternative to medical treatment for early pT1
      lesions and is often the only remaining curative solution in patients previously
      treated with radiotherapy. In cases of bulky resection, or when there is a past
      medical history of radiotherapy, a tissue reconstruction by forearm free-flap may
      be indicated.

PMID- 29032419
TI  - Objective assessment of the reliability of the House-Brackmann and Fisch grading
      of synkinesis.
AB  - The objective of this paper is to assess synkinesis associated with post paretic
      voluntary facial movements using the objective OSCAR method and to investigate
      the correlation between synkinesis and paresis to compare the objective results
      with the subjective scaling systems of Fisch and House-Brackmann. The development
      of an objective assessment of synkinesis with the OSCAR method is focused on the
      clinically most relevant eye-mouth and forehead-mouth synkinetic movements.
      Thirteen patients with unilateral facial paralysis and synkinesis of the
      University Hospital Zurich were examined. Two types of clinically relevant facial
      synkinesis were found: a maximal synkinesis and a relative synkinesis. Neither
      Synkinesis-Index correlates well with the underlying degree of global facial
      palsy. The relative Synkinesis-Index (rSI) correlates well with the subjective
      evaluation of synkinesis according to the Fisch Grading, but shows a poor
      correlation with the traditional House-Brackmann grading. Therefore a single
      scaling index combining the degree of facial nerve palsy and synkinesis is
      inappropriate and we propose the use of two independent scaling systems for the
      evaluation of facial palsy: one for the voluntary facial movements, the other for
      the involuntary synkinetic movements. The adequate evaluation of the post paretic
      face should include the results of both scaling systems.

PMID- 29032420
TI  - Cochlear implantation with the nucleus slim modiolar electrode (CI532): a
      preliminary experience.
AB  - To combine the benefits of perimodiolar stimulation with minimal insertion
      trauma, a thin, pre-curved electrode (CI532) was recently developed by Cochlear
      Ltd. (Sidney). This array is held straight prior to insertion by an external
      polymer reloadable sheath that is removed after full electrode insertion. Sixty
      seven patients suffering from severe-to-profound sensorineural hearing loss (mean
      age 42.2 years; mean duration of the hearing loss 19.6 years; mean PTA thresholds
      at 250-2000 Hz 92.4 dB HL) were implanted with the CI532. Mean duration of
      surgery was 58.7 min. In 61 patients, a round window (RW) approach was used. In
      the remaining six cases, a cochleostomy was done because of RW ossification.
      Impedances and NRT for each electrode are reported. NRT ratio average value was
      0.86 +/- 0.12 predicting correct scala tympani electrode placement. Post
      operative PTA threshold in the implanted ear was 102.9 dB HL. Finally, speech
      recognition level in quiet at 65 dB HL was 44.6%, after a short follow-up (mean
      5.2 months). Our preliminary experience with the new CI532 shows good surgical,
      electrophysiological, and audiological outcomes. In particular, our results are
      promising regarding the possibility to achieve minimal insertion trauma and good
      residual hearing preservation with the use of a deep inserted close modiolar
      electrode.

PMID- 29032421
TI  - Computer-based radiological longitudinal evaluation of meningiomas following
      stereotactic radiosurgery.
AB  - PURPOSE: Stereotactic radiosurgery (SRS) is a common treatment for intracranial
      meningiomas. SRS is planned on a pre-therapy gadolinium-enhanced T1-weighted MRI
      scan (Gd-T1w MRI) in which the meningioma contours have been delineated. Post-SRS
      therapy serial Gd-T1w MRI scans are then acquired for longitudinal treatment
      evaluation. Accurate tumor volume change quantification is required for treatment
      efficacy evaluation and for treatment continuation. METHOD: We present a new
      algorithm for the automatic segmentation and volumetric assessment of meningioma
      in post-therapy Gd-T1w MRI scans. The inputs are the pre- and post-therapy Gd-T1w
      MRI scans and the meningioma delineation in the pre-therapy scan. The output is
      the meningioma delineations and volumes in the post-therapy scan. The algorithm
      uses the pre-therapy scan and its meningioma delineation to initialize an
      extended Chan-Vese active contour method and as a strong patient-specific
      intensity and shape prior for the post-therapy scan meningioma segmentation. The
      algorithm is automatic, obviates the need for independent tumor localization and
      segmentation initialization, and incorporates the same tumor delineation criteria
      in both the pre- and post-therapy scans. RESULTS: Our experimental results on
      retrospective pre- and post-therapy scans with a total of 32 meningiomas with
      volume ranges 0.4-26.5 cm[Formula: see text] yield a Dice coefficient of
      [Formula: see text]% with respect to ground-truth delineations in post-therapy
      scans created by two clinicians. These results indicate a high correspondence to
      the ground-truth delineations. CONCLUSION: Our algorithm yields more reliable and
      accurate tumor volume change measurements than other stand-alone segmentation
      methods. It may be a useful tool for quantitative meningioma prognosis evaluation
      after SRS.

PMID- 29032422
TI  - The deep layer of the tractus iliotibialis and its relevance when using the
      direct anterior approach in total hip arthroplasty: a cadaver study.
AB  - INTRODUCTION: Surgical approaches through smaller incisions reveal less of the
      underlying anatomy, and therefore, detailed knowledge of the local anatomy and
      its variations is important in minimally invasive surgery. The aim of this study
      was to determine the location, extension, and histomorphology of the deep layer
      of the iliotibial band during minimally invasive hip surgery using the direct
      anterior approach (DAA). MATERIALS AND METHODS: The morphology of the iliotibial
      tract was determined in this cadaver study on 40 hips with reference to the
      anterior superior iliac spine and the tibia. The deep layer of the tractus
      iliotibialis was exposed up to the hip-joint capsule and length and width
      measurements taken. Sections of the profound iliotibial tract were removed from
      the hips and the thickness of the sections was determined microscopically after
      staining. RESULTS: The superficial tractus iliotibialis had a length of 50.1 (SD
      3.8) cm, while tensor fasciae latae total length was 18 (SD 2) cm [unattached 15
      (SD 2.5) cm]. Length and width of the deep layer of the tractus iliotibialis were
      10.4 (SD 1.3) * 3.3 (SD 0.6) cm. The deep iliotibial band always extended from
      the distal part of the tensor fascia latae (TFL) muscle to the lateral part of
      the hip capsule (mean maximum thickness 584 MUm). Tractus iliotibialis deep layer
      morphology did not correlate to other measurements taken (body length, thigh
      length, and TFL length). CONCLUSIONS: The length of the deep layer is dependent
      on the TFL, since the profound part of the iliotibial band reaches from the TFL
      to the hip-joint capsule. The deep layer covers the hip-joint capsule, rectus,
      and lateral vastus muscles in the DAA interval. To access the precapsular fat pad
      and the hip-joint capsule, the deep layer has to be split in all approaches that
      use the direct anterior interval.

PMID- 29032423
TI  - The pathogenesis shared between abdominal aortic aneurysms and intracranial
      aneurysms: a microarray analysis.
AB  - Abdominal aortic aneurysms (AAAs) and intracranial saccular aneurysms (IAs) are
      the most common types of aneurysms. This study was to investigate the common
      pathogenesis shared between these two kinds of aneurysms. We collected 12 IAs
      samples and 12 control arteries from the Beijing Tiantan Hospital and performed
      microarray analysis. In addition, we utilized the microarray datasets of IAs and
      AAAs from the Gene Expression Omnibus (GEO), in combination with our microarray
      results, to generate messenger RNA expression profiles for both AAAs and IAs in
      our study. Functional exploration and protein-protein interaction (PPI) analysis
      were performed. A total of 727 common genes were differentially expressed (404
      was upregulated; 323 was downregulated) for both AAAs and IAs. The GO and pathway
      analyses showed that the common dysregulated genes were mainly enriched in
      vascular smooth muscle contraction, muscle contraction, immune response, defense
      response, cell activation, IL-6 signaling and chemokine signaling pathways, etc.
      The further protein-protein analysis identified 35 hub nodes, including TNF, IL6,
      MAPK13, and CCL5. These hub node genes were enriched in inflammatory response,
      positive regulation of IL-6 production, chemokine signaling pathway, and T/B cell
      receptor signaling pathway. Our study will gain new insight into the molecular
      mechanisms for the pathogenesis of both types of aneurysms and provide new
      therapeutic targets for the patients harboring AAAs and IAs.

PMID- 29032424
TI  - Not just gene expression: 3D implications of chromatin modifications during
      sexual plant reproduction.
AB  - DNA methylation and histone modifications are epigenetic changes on a DNA
      molecule that alter the three-dimensional (3D) structure locally as well as
      globally, impacting chromatin looping and packaging on a larger scale. Epigenetic
      marks thus inform higher-order chromosome organization and placement in the
      nucleus. Conventional epigenetic marks are joined by chromatin modifiers like
      cohesins, condensins and membrane-anchoring complexes to support particularly 3D
      chromosome organization. The most popular consequences of epigenetic
      modifications are gene expression changes, but chromatin modifications have
      implications beyond this, particularly in actively dividing cells and during
      sexual reproduction. In this opinion paper, we will focus on epigenetic
      mechanisms and chromatin modifications during meiosis as part of plant sexual
      reproduction where 3D management of chromosomes and re-organization of chromatin
      are defining features and prime tasks in reproductive cells, not limited to
      modulating gene expression. Meiotic chromosome organization, pairing and synapsis
      of homologous chromosomes as well as distribution of meiotic double-strand breaks
      and resulting crossovers are presumably highly influenced by epigenetic
      mechanisms. Special mobile small RNAs have been described in anthers, where these
      so-called phasiRNAs seem to direct DNA methylation in meiotic cells.
      Intriguingly, many of the mentioned developmental processes make use of
      epigenetic changes and small RNAs in a manner other than gene expression changes.
      Widening our approaches and opening our mind to thinking three-dimensionally
      regarding epigenetics in plant development holds high promise for new discoveries
      and could give us a boost for further knowledge.

PMID- 29032425
TI  - Heterologous expression of wheat TaRUB1 gene enhances disease resistance in
      Arabidopsis thaliana.
AB  - KEY MESSAGE: Expression of TaRUB1 gene in Arabidopsis thaliana elevates the level
      of disease-related genes in response to pathogen invasion through the
      accumulation of callose, necrotic cells, and the outbreak of ROS. Ubiquitin (Ub)
      and ubiquitin-like proteins are highly conserved in sequence and can covalently
      bind and modify many intracellular proteins which can be recognized and degraded
      by 26S proteasome. Post-translational modification of proteins has become a hot
      research spot today. In the previous study, a cDNA of related-to-ubiquitin
      protein belonged to ubiquitin-like proteins, whose spatial structure comprised Ub
      and NEDD8, was obtained from wheat SN6306 by suppression-subtractive
      hybridization and was named TaRUB1. TaRUB1 is induced by wheat powdery mildew and
      significantly upregulated in resistant wheat SN6306. In this study, heterologous
      expression of TaRUB1 in A. thaliana was used to study the function of this gene
      in response to pathogen Pseudomonas syringae pv. Tomato DC3000 (Pst DC3000).
      Transgenic A. thaliana showed relatively fewer disease symptoms, accompanied by
      common inhibition of living body parasitic defense responses, accumulation of
      more callose and reactive oxygen species (ROS), and concentrated cell death,
      simultaneously antioxidant enzyme activities of superoxide dismutase, peroxidase,
      catalase, and ascorbate peroxidase were higher than those in wild-type (WT) plant
      after infection with Pst DC3000. Meanwhile, hypersensitive cell death, which was
      possibly ROS burst, was also observed in transgenic A. thaliana. By quantitative
      reverse transcription-polymerase chain reaction analysis, some marker genes for
      hypersensitive response showed significantly higher transcriptional expression
      level in transgenic A. thaliana, which activates system-acquired resistance, than
      that of WT plants. Heterologous expression of TaRUB1 can significantly enhance
      resistance to Pst DC3000 in A. thaliana, suggesting that TaRUB1 is related to
      plant disease resistance.

PMID- 29032426
TI  - Transgenerational stress-adaption: an opportunity for ecological epigenetics.
AB  - In the recent years, there has been considerable interest to investigate the
      adaptive transgenerational plasticity of plants and how a "stress memory" can be
      transmitted to the following generation. Although, increasing evidence suggests
      that transgenerational adaptive responses have widespread ecological relevance,
      the underlying epigenetic processes have rarely been elucidated. On the other
      hand, model plant species have been deeply investigated in their genome-wide
      methylation landscape without connecting this to the ecological reality of the
      plant. What we need is the combination of an ecological understanding which plant
      species would benefit from transgenerational epigenetic stress-adaption in their
      natural habitat, combined with a deeper molecular analysis of non-model
      organisms. Only such interdisciplinary linkage in an ecological epigenetic study
      could unravel the full potential that epigenetics could play for the
      transgenerational stress-adaption of plants.

PMID- 29032428
TI  - Usability Operations on Touch Mobile Devices for Users with Autism.
AB  - The Autistic Spectrum Disorder is a cognitive disorder that affects the cognitive
      and motor skills; due that, users cannot perform digital and fine motor tasks. It
      is necessary to create software applications that adapt to the abilities of these
      users. In recent years has been an increase in the research of the use of
      technology to support autistic users to develop their communication skills and to
      improve learning. However, the applications' usability for disable users is not
      assessed objectively as the existing models do not consider interaction operators
      for disable users. This article focuses on identifying the operations that can
      easily be performed by autistic users following the metrics of KML-GOMS, TLM and
      FLM. In addition, users of typical development were included in order to do a
      comparison between both types of users. The experiment was carried out using four
      applications designed for autistic users. Participants were subjects divided in
      two groups: level 1 and level 2 autistic users, and a group of users of typical
      development. During the experimentation, users performed a use case for each
      application; the time needed to perform each task was measured. Results show that
      the easiest operations for autistic users are K (Keystroke), D (Drag), Initial
      Act (I) and Tapping (T).

PMID- 29032427
TI  - Soft mechanical stimulation induces a defense response against Botrytis cinerea
      in strawberry.
AB  - KEY MESSAGE: Genes associated with plant mechanical stimulation were found in
      strawberry genome. A soft mechanical stimulation (SMS) induces molecular and
      biochemical changes in strawberry plants, conferring protection against Botrytis
      cinerea. Plants have the capacity to induce a defense response after exposure to
      abiotic stresses acquiring resistance towards pathogens. It was reported that
      when leaves of Arabidopsis thaliana were wounded or treated with a soft
      mechanical stimulation (SMS), they could resist much better the attack of the
      fungal pathogen Botrytis cinerea, and this effect was accompanied by an oxidative
      burst and the expression of touch-inducible genes (TCH). However, no further work
      was carried out to better characterize the induced defense response. In this
      paper, we report that TCH genes were identified for first time in the genomes of
      the strawberry species Fragaria ananassa (e.g. FaTCH2, FaTCH3, FaTCH4 and
      FaCML39) and Fragaria vesca (e.g. FvTCH2, FvTCH3, FvTCH4 and FvCML39).
      Phylogenetic studies revealed that F. ananassa TCH genes exhibited high
      similarity with the orthologous of F. vesca and lower with A. thaliana ones. We
      also present evidence that after SMS treatment on strawberry leaves, plants
      activate a rapid oxidative burst, callose deposition, and the up-regulation of
      TCH genes as well as plant defense genes such as FaPR1, FaCHI2-2, FaCAT, FaACS1
      and FaOGBG-5. The latter represents the first report showing that TCH- and
      defense-induced genes participate in SMS-induced resistance in plants, bringing a
      rational explanation why plants exposed to a SMS treatment acquired an enhance
      resistance toward B. cinerea.

PMID- 29032430
TI  - The Impacts of Soil Fertility and Salinity on Soil Nitrogen Dynamics Mediated by
      the Soil Microbial Community Beneath the Halophytic Shrub Tamarisk.
AB  - Nitrogen (N) is one of the most common limiting nutrients for primary production
      in terrestrial ecosystems. Soil microbes transform organic N into inorganic N,
      which is available to plants, but soil microbe activity in drylands is sometimes
      critically suppressed by environmental factors, such as low soil substrate
      availability or high salinity. Tamarisk (Tamarix spp.) is a halophytic shrub
      species that is widely distributed in the drylands of China; it produces litter
      enriched in nutrients and salts that are thought to increase soil fertility and
      salinity under its crown. To elucidate the effects of tamarisks on the soil
      microbial community, and thus N dynamics, by creating "islands of fertility" and
      "islands of salinity," we collected soil samples from under tamarisk crowns and
      adjacent barren areas at three habitats in the summer and fall. We analyzed soil
      physicochemical properties, inorganic N dynamics, and prokaryotic community
      abundance and composition. In soils sampled beneath tamarisks, the N
      mineralization rate was significantly higher, and the prokaryotic community
      structure was significantly different, from soils sampled in barren areas,
      irrespective of site and season. Tamarisks provided suitable nutrient conditions
      for one of the important decomposers in the area, Verrucomicrobia, by creating
      "islands of fertility," but provided unsuitable salinity conditions for other
      important decomposers, Flavobacteria, Gammaproteobacteria, and
      Deltaproteobacteria, by mitigating salt accumulation. However, the quantity of
      these decomposers tended to be higher beneath tamarisks, because they were
      relatively unaffected by the small salinity gradient created by the tamarisks,
      which may explain the higher N mineralization rate beneath tamarisks.

PMID- 29032429
TI  - DNA damage and oxidative stress induced by seizures are decreased by
      anticonvulsant and neuroprotective effects of lobeline, a candidate to treat
      alcoholism.
AB  - The alkaloid lobeline (Lob) has been studied due to its potential use in
      treatment of drug abuse. This study evaluates the possible anticonvulsant and
      neuroprotective activities of Lob to obtain new information on its properties
      that could confirm it as a candidate in the treatment of alcohol addiction. The
      anticonvulsant effect of Lob was evaluated using a pilocarpine-induced seizure
      model. In addition, possible neuroprotective effects were investigated measuring
      DNA damage using the comet assay, assessing free radical levels by
      dichlorofluorescein diacetate (DCF) oxidation, and measuring the antioxidant
      potential using the alpha, alpha-diphenyl-beta-picrylhydrazyl (DPPH) scavenging
      assay, besides measuring superoxide dismutase (SOD) and catalase (CAT) enzyme
      activities in brain tissues. Lobeline increased the latency to the first seizure
      and decreased the percentage of seizures in a similar way as diazepam, used as
      control. DNA damage induced by Pil and hydrogen peroxide were decreased in
      hippocampus and cerebral cortex from mice treated with Lob. The levels of free
      radicals and CAT activity increased in cortex and hippocampus, respectively, in
      mice treated with Pil. Lobeline decreased CAT in hippocampus, leading to similar
      values as in the saline negative control. In conclusion, Lob has anticonvulsant
      and neuroprotective actions that may be mediated by antioxidant-like mechanisms,
      indicating its potential as candidate drug in alcoholism therapy.

PMID- 29032431
TI  - Identification of coronary artery anatomy on dual-source cardiac computed
      tomography before arterial switch operation in newborns and young infants:
      comparison with transthoracic echocardiography.
AB  - BACKGROUND: Considering inherent limitations of transthoracic echocardiography,
      the diagnostic accuracy of cardiac CT in identifying coronary artery anatomy
      before arterial switch operation needs to be investigated with recently improved
      coronary artery visibility using electrocardiogram (ECG)-synchronized dual-source
      CT. OBJECTIVE: To compare diagnostic accuracy between cardiac CT using a dual
      source scanner and transthoracic echocardiography in identifying coronary artery
      anatomy before arterial switch operation in newborns and young infants. MATERIALS
      AND METHODS: The study included 101 infants (median age 4 days, range 0 days to
      10 months; M:F=78:23) who underwent ECG-synchronized cardiac dual-source CT and
      transthoracic echocardiography before arterial switch operation between July 2011
      and December 2016. We evaluated and classified coronary artery anatomy on cardiac
      CT and transthoracic echocardiography. With the surgical findings as the
      reference standard, we compared the diagnostic accuracy for identifying coronary
      artery anatomy between cardiac CT and transthoracic echocardiography. RESULTS:
      The most common coronary artery pattern was the usual pattern (left coronary
      artery from sinus 1 and right coronary artery from sinus 2; 64.4%, 65/101),
      followed by a single coronary artery from sinus 2 and a conal branch from sinus 1
      (7.9%, 8/101), the inverted pattern (5.9%, 6/101), the right coronary artery and
      left anterior descending artery from sinus 1 and the left circumflex artery from
      sinus 2 (5.9%, 6/101), and others. In 96 infants with surgically proven coronary
      artery anatomy, the diagnostic accuracy of cardiac CT was significantly higher
      than that of transthoracic echocardiography (91.7%, 88/96 vs. 54.2%, 52/96;
      P<0.0001). CONCLUSION: Diagnostic accuracy of cardiac CT is significantly higher
      than that of echocardiography in identifying coronary artery anatomy before
      arterial switch operation in newborns and young infants.

PMID- 29032432
TI  - Relationship between rice yield and climate variables in southwest Nigeria using
      multiple linear regression and support vector machine analysis.
AB  - This study examines the variations of climate variables and rice yield and
      quantifies the relationships among them using multiple linear regression,
      principal component analysis, and support vector machine (SVM) analysis in
      southwest Nigeria. The climate and yield data used was for a period of 36 years
      between 1980 and 2015. Similar to the observed decrease (P < 0.001) in rice
      yield, pan evaporation, solar radiation, and wind speed declined significantly.
      Eight principal components exhibited an eigenvalue > 1 and explained 83.1% of the
      total variance of predictor variables. The SVM regression function using the
      scores of the first principal component explained about 75% of the variance in
      rice yield data and linear regression about 64%. SVM regression between annual
      solar radiation values and yield explained 67% of the variance. Only the first
      component of the principal component analysis (PCA) exhibited a clear long-term
      trend and sometimes short-term variance similar to that of rice yield. Short-term
      fluctuations of the scores of the PC1 are closely coupled to those of rice yield
      during the 1986-1993 and the 2006-2013 periods thereby revealing the inter-annual
      sensitivity of rice production to climate variability. Solar radiation stands out
      as the climate variable of highest influence on rice yield, and the influence was
      especially strong during monsoon and post-monsoon periods, which correspond to
      the vegetative, booting, flowering, and grain filling stages in the study area.
      The outcome is expected to provide more in-depth regional-specific climate-rice
      linkage for screening of better cultivars that can positively respond to future
      climate fluctuations as well as providing information that may help optimized
      planting dates for improved radiation use efficiency in the study area.

PMID- 29032433
TI  - Diffuse mesangial sclerosis in a PDSS2 mutation-induced coenzyme Q10 deficiency.
AB  - BACKGROUND: A 7-month-old male infant was admitted because he was suffering from
      nephrotic syndrome, along with encephalomyopathy, hypertrophic cardiomyopathy,
      clinically suspected deafness and retinitis pigmentosa, and an elevated serum
      lactate level. METHODS: Coenzyme Q10 supplementation was started because of the
      clinical suspicion of primary CoQ10 deficiency. Despite intensive efforts, he
      passed away 4 weeks after admission. RESULTS: The results of genetic tests,
      available postmortem, explored two hitherto undescribed mutations in the PDSS2
      gene. Both were located within the polyprenyl synthetase domain. Clinical exome
      sequencing revealed a heterozygous missense mutation in exon 3, and our in-house
      joint-analysis algorithm detected a heterozygous large 2923-bp deletion that
      affected the 5 prime end of exon 8. Other causative defects in the CoQ10 and
      infantile nephrosis-related genes examined were not found. A postmortem
      histological, immunohistochemical, and electron microscopic evaluation of the
      glomeruli revealed collapsing-sclerosing lesions consistent with diffuse
      mesangial sclerosis. The extrarenal alterations included hypertrophic
      cardiomyopathy and diffuse alveolar damage. A histological evaluation of the
      central nervous system and skeletal muscles did not demonstrate any obvious
      abnormality. CONCLUSIONS: Until now, the clinical features and the mutational
      status of 6 patients with a PDSS2 gene defect have been reported in the English
      literature. Here, we describe for the first time detailed kidney morphology
      features in a patient with nephrotic syndrome carrying mutations in the PDSS2
      gene.

PMID- 29032434
TI  - The influence of mitomycin C concentration on the outcome of trabeculectomy in
      uveitic glaucoma.
AB  - PURPOSE: To evaluate the influence of mitomycin C (MMC) concentration on the
      outcome of trabeculectomy in uveitic glaucoma. METHODS: Retrospective comparative
      study included 50 patients who underwent MMC-enhanced trabeculectomy for
      uncontrolled uveitic glaucoma. Patients were divided into two groups based on the
      concentration of MMC used during trabeculectomy (high [0.04%] or low [0.02%]).
      The main outcome measures were: the intraocular pressure (IOP), the number of
      antiglaucoma medications, the need for further glaucoma surgeries, and
      trabeculectomy success. RESULTS: There were no differences in the IOP nor
      antiglaucoma medications. The success rates were 76.0 and 68.0%, while the
      failure rates were 24.0 and 32.0% in the 0.02 and 0.04% MMC groups, respectively.
      CONCLUSION: Trabeculectomy augmented with low (0.02%) MMC concentration seems to
      have comparable outcomes in uveitic glaucoma compared with high (0.04%)
      concentration.

PMID- 29032435
TI  - Environmental factors associated with ocular morbidity among children in three
      ecological regions of Nepal: a phase II Nepal Pediatric Ocular Diseases Study.
AB  - PURPOSE: The Nepal Pediatric Ocular Diseases Study (NPODS) was a 3-year (January
      2012-December 2014) longitudinal study carried out in three ecological regions of
      Nepal to understand the magnitude of the problems of childhood ocular morbidity
      and blindness. Based on the results of this study, a second phase of NPODS was
      undertaken to understand the risk factors associated with childhood ocular
      diseases. This paper analyzes environmental factors. METHOD: This was a nested
      case-control study with study population selected from the same cohort of
      children included in the baseline survey of NPODS. The study areas were the same
      (three districts from three ecological regions: Sindhupalchowk from mountain,
      Makawanpur from hills, and Sarlahi from terai). After sample size calculation,
      cases and controls were taken in 1:4 ratio and matched for age, sex, and
      location. RESULTS: A total of 830 children (166 cases, 664 controls) were
      selected with 5.4 % of cases and 2.7 % of control participants nonresponders.
      Among environmental factors, children who stayed with their mother during
      cooking, who had with fewer windows in their kitchen, and who used dusty roads to
      school had significant association with ocular morbidities. Similarly, children
      with cable TV in their house had higher chance of having refractive error.
      CONCLUSIONS: Many of the environmental factors associated with ocular diseases in
      children are modifiable. Improving the household environment is likely to
      effectively decrease the burden of eye diseases. The association of refractive
      error with increased indoor and near activities is an important finding, reported
      herein for the first time in Nepalese children.

PMID- 29032436
TI  - Does capitated managed care affect budget predictability? Evidence from Medicaid
      programs.
AB  - As the second largest item in the budget of every US state, Medicaid budget
      stability and financial transparency have significance for every state. This
      study is the first to test whether managed care enrollment reduces the variance
      of Medicaid spending, in contrast to the focus of the existing literature on
      spending levels. This variance bears directly on whether budget constrained
      states whether budget constrained states benefit from managed care in the form of
      stabilized spending, leading to improved budget predictability. Capitated
      payments stabilize spending at the margin, but the effects may be unobservable in
      aggregate due to variation in enrollment, which is directly measured in the
      analysis, or selection bias, which is unobserved. Although the majority of
      Medicaid enrollees are in managed care, the study shows that managed care use has
      been concentrated among the enrollees with the most stable spending, resulting in
      only small gains to budget predictability. This finding is robust to the
      exclusion of the claims expenditures that exhibit the most variance.

PMID- 29032437
TI  - Scale Heterogeneity in Healthcare Discrete Choice Experiments: A Primer.
AB  - Discrete choice experiments (DCEs) are used to quantify the preferences of
      specified sample populations for different aspects of a good or service and are
      increasingly used to value interventions and services related to healthcare.
      Systematic reviews of healthcare DCEs have focussed on the trends over time of
      specific design issues and changes in the approach to analysis, with a more
      recent move towards consideration of a specific type of variation in preferences
      within the sample population, called taste heterogeneity, noting rises in the
      popularity of mixed logit and latent class models. Another type of variation,
      called scale heterogeneity, which relates to differences in the randomness of
      choice behaviour, may also account for some of the observed 'differences' in
      preference weights. The issue of scale heterogeneity becomes particularly
      important when comparing preferences across subgroups of the sample population as
      apparent differences in preferences could be due to taste and/or choice
      consistency. This primer aims to define and describe the relevance of scale
      heterogeneity in a healthcare context, and illustrate key points, with a
      simulated data set provided to readers in the Online appendix.

PMID- 29032438
TI  - Improvements in Quality-Adjusted Life Years and Cost-Utility After
      Pharmacotherapy for Premenstrual Dysphoric Disorder: A Retrospective Study.
AB  - BACKGROUND AND OBJECTIVE: To investigate the cost-effectiveness of
      pharmacotherapy for premenstrual dysphoric disorder (PMDD), a relatively new
      classification of depressive disorder that is characterized by recurrent
      depression during the premenstrual phase of the menstrual cycle. METHODS: We
      performed a retrospective analysis of data from 49 previously untreated PMDD
      patients who visited our psychiatric department between October 2013 and February
      2016 and received pharmacotherapy for 3 or 6 subsequent menstrual cycles. Quality
      adjusted life years (QALYs) were estimated across individual menstrual cycles
      using mean EuroQoL-5D values. Direct costs per patient were estimated in order to
      conduct a preliminary cost-effectiveness analysis. RESULTS: Pharmacotherapy
      produced a 0.190-point increase in mean EuroQoL-5D score per menstrual cycle
      after 6 menstrual cycles and an improvement of approximately 0.2 QALYs. Based on
      direct costs of 156,000 yen per patient, the cost-effectiveness of
      pharmacotherapy was calculated to be 823,000 yen per QALY. A cost-effectiveness
      acceptability curve analysis indicated that escitalopram tended to be superior to
      sertraline when willingness to pay per QALY was over 4,000,000 yen, whereas
      sertraline was superior when willingness to pay was below 2,000,000 yen.
      CONCLUSIONS: Pharmacotherapy is cost effective for the treatment of PMDD.
      Moreover, escitalopram is a more cost-effective option than sertraline when
      willingness to pay is sufficiently high.

PMID- 29032439
TI  - The Application of Chironomid Pupal Exuvial Technique (CPET) for Ecological
      Analysis in a Neotropical Large River System.
AB  - This field ecological study, based on the chironomid pupal exuvial technique
      (CPET), is new for the Parana River and proposes an efficient tool to be used in
      future ecological approaches and biomonitoring. Drifting of pupal exuviae in a
      river-floodplain system of the Middle Parana River floodplain was represented by
      34 Chironomidae taxa, being the characteristic association obtained from the
      CPET: Lopescladius, Onconeura, Paralauterborniella, Polypedilum, and Harnischia
      complex. Diversity, richness, dominance, total density, and density of dominant
      taxa were different between the longitudinal and lateral dimensions but not
      between hydrologic phases, with a greater diversity and richness in the main
      channel of the river and higher density and dominance in floodplain habitats. The
      species turnover is the dominant process in structuring studied assemblages in
      spatial and temporal analysis, increasing in the floodplain habitats and in low
      water phase. The results obtained showed that drifting exuviae in the
      longitudinal axis were coming from different assemblages and environments of a
      wider area (regional), while exuviae recorded in the connections of the
      floodplain environments in the lateral dimension could reflect the local
      assemblages. We demonstrated the ecological value of CPET studies to interpret
      the attributes of Chironomidae assemblage in river-floodplain systems of large
      rivers in an integrated way.

PMID- 29032441
TI  - Characteristics of PAHs in farmland soil and rainfall runoff in Tianjin, China.
AB  - Rainfall runoff can remove certain amounts of pollutants from contaminated
      farmland soil and result in a decline in water quality. However, the leaching
      behaviors of polycyclic aromatic hydrocarbons (PAHs) with rainfall have been
      rarely reported due to wide variations in the soil compositions, rainfall
      conditions, and sources of soil PAHs in complex farmland ecosystems. In this
      paper, the levels, spatial distributions, and composition profiles of PAHs in 30
      farmland soil samples and 49 rainfall-runoff samples from the Tianjin region in
      2012 were studied to investigate their leaching behaviors caused by rainfall
      runoff. The contents of the Sigma16PAHs ranged from 58.53 to 3137.90 MUg/kg in
      the soil and 146.58 to 3636.59 MUg/L in the runoff. In total, most of the soil
      sampling sites (23 of 30) were contaminated, and biomass and petroleum combustion
      were proposed as the main sources of the soil PAHs. Both the spatial
      distributions of the soil and the runoff PAHs show a decreasing trend moving away
      from the downtown, which suggested that the leaching behaviors of PAHs in a
      larger region during rainfall may be mainly affected by the compounds themselves.
      In addition, 4- and 5-ring PAHs are the dominant components in farmland soil and
      3- and 4-ring PAHs dominate the runoff. Comparisons of the PAH pairs and
      enrichment ratios showed that acenaphthylene, acenaphthene, benzo[a]anthracene,
      chrysene, and fluoranthene were more easily transferred into water systems from
      soil than benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[ghi]perylene, and
      indeno[123-cd]pyrene, which indicated that PAHs with low molecular weight are
      preferentially dissolved due to their higher solubility compared to those with
      high molecular weight.

PMID- 29032440
TI  - Vasculitis and vasculitis-like manifestations in monogenic autoinflammatory
      syndromes.
AB  - Monogenic autoinflammatory syndromes are a rare group of disorders characterized
      by periodic episodes of systemic inflammation of endogenous origin. Sometimes,
      these diseases may present with features akin to vasculitis. We conducted a
      literature review on such vasculitic manifestations in described monogenic
      autoinflammatory syndromes utilizing the Online Mendelian Inheritance in Man
      (OMIM), Medline, and Scopus databases. Our search identified that Familial
      Mediterranean fever (FMF) can manifest with features of either small, medium,
      large, or variable-vessel vasculitis. Stimulator of interferon gene (STING)
      associated vasculopathy of infancy (SAVI) is an interferonopathy that can mimic
      the presentation of medium-vessel or small-vessel vasculitis, whereas deficiency
      of adenosine deaminase 2 (DADA2) is another such mimic of medium-vessel
      vasculitis, associated in a significant number of patients with features of
      immunodeficiency. Occasional reports exist of vasculitic manifestations in tumor
      necrosis factor (TNF) receptor-associated periodic fever syndrome (TRAPS) and
      chronic infantile neurologic cutaneous and articular disorder (CINCA), whereas
      mevalonate kinase deficiency can also mimic the presentation of small- or medium
      vessel vasculitis. Clinicians should be aware of the possibility of
      autoinflammatory disease presenting as vasculitis to diagnose and treat the same
      appropriately.

PMID- 29032442
TI  - The Influence of Peers During Adolescence: Does Homophobic Name Calling by Peers
      Change Gender Identity?
AB  - Adolescents actively evaluate their identities during adolescence, and one of the
      most salient and central identities for youth concerns their gender identity.
      Experiences with peers may inform gender identity. Unfortunately, many youth
      experience homophobic name calling, a form of peer victimization, and it is
      unknown whether youth internalize these peer messages and how these messages
      might influence gender identity. The goal of the present study was to assess the
      role of homophobic name calling on changes over the course of an academic year in
      adolescents' gender identity. Specifically, this study extends the literature
      using a new conceptualization and measure of gender identity that involves
      assessing how similar adolescents feel to both their own- and other-gender peers
      and, by employing longitudinal social network analyses, provides a rigorous
      analytic assessment of the impact of homophobic name calling on changes in these
      two dimensions of gender identity. Symbolic interaction perspectives-the "looking
      glass self"-suggest that peer feedback is incorporated into the self-concept. The
      current study tests this hypothesis by determining if adolescents respond to
      homophobic name calling by revising their self-view, specifically, how the self
      is viewed in relation to both gender groups. Participants were 299 6th grade
      students (53% female). Participants reported peer relationships, experiences of
      homophobic name calling, and gender identity (i.e., similarity to own- and other
      gender peers). Longitudinal social network analyses revealed that homophobic name
      calling early in the school year predicted changes in gender identity over time.
      The results support the "looking glass self" hypothesis: experiencing homophobic
      name calling predicted identifying significantly less with own-gender peers and
      marginally more with other-gender peers over the course of an academic year. The
      effects held after controlling for participant characteristics (e.g., gender),
      social network features (e.g., norms), and peer experiences (e.g., friend
      influence, general victimization). Homophobic name calling emerged as a form of
      peer influence that changed early adolescent gender identity, such that
      adolescents in this study appear to have internalized the messages they received
      from peers and incorporated these messages into their personal views of their own
      gender identity.

PMID- 29032443
TI  - Teacher Support, Peer Acceptance, and Engagement in the Classroom: A Three-Wave
      Longitudinal Study in Late Childhood.
AB  - Although research has examined the bivariate effects of teacher support, peer
      acceptance, and engagement, it remains unclear how these key classroom
      experiences evolve together, especially in late childhood. This study aims to
      provide a detailed picture of their transactional relations in late childhood. A
      sample of 586 children (M age  = 9.26 years, 47.1% boys) was followed from fourth
      to sixth grade. Teacher support and engagement were student-reported and peer
      acceptance was peer-reported. Autoregressive cross-lagged models revealed unique
      longitudinal effects of both peer acceptance and teacher support on engagement,
      and of peer acceptance on teacher support. No reverse effects of engagement on
      peer acceptance or teacher support were found. The study underscores the
      importance of examining the relative contribution of several social actors in the
      classroom. Regarding interventions, improving both peer acceptance and teacher
      support can increase children's engagement, and augmenting peer acceptance can
      help to increase teacher support.

PMID- 29032445
TI  - Monitoring coal mine changes and their impact on landscape patterns in an alpine
      region: a case study of the Muli coal mine in the Qinghai-Tibet Plateau.
AB  - The Muli coal mine is the largest open-cast coal mine in the Qinghai-Tibet
      Plateau, and it consists of two independent mining sites named Juhugeng and
      Jiangcang. It has received much attention due to the ecological problems caused
      by rapid expansion in recent years. The objective of this paper was to monitor
      the mining area and its surrounding land cover over the period 1976-2016
      utilizing Landsat images, and the network structure of land cover changes was
      determined to visualize the relationships and pattern of the mining-induced land
      cover changes. In addition, the responses of the surrounding landscape pattern
      were analysed by constructing gradient transects. The results show that the
      mining area was increasing in size, especially after 2000 (increased by 71.68
      km2), and this caused shrinkage of the surrounding lands, including alpine meadow
      wetland (53.44 km2), alpine meadow (6.28 km2) and water (6.24 km2). The network
      structure of the mining area revealed the changes in lands surrounding the mining
      area. The impact of mining development on landscape patterns was mainly
      distributed within a range of 1-6 km. Alpine meadow wetland was most affected in
      Juhugeng, while alpine meadow was most affected in Jiangcang. The results of this
      study provide a reference for the ecological assessment and restoration of the
      Muli coal mine land.

PMID- 29032444
TI  - Modulating signaling networks by CRISPR/Cas9-mediated transposable element
      insertion.
AB  - In a recent past, transposable elements (TEs) were referred to as selfish genetic
      components only capable of copying themselves with the aim of increasing the odds
      of being inherited. Nonetheless, TEs have been initially proposed as positive
      control elements acting in synergy with the host. Nowadays, it is well known that
      TE movement into host genome comprises an important evolutionary mechanism
      capable of increasing the adaptive fitness. As insights into TE functioning are
      increasing day to day, the manipulation of transposition has raised an
      interesting possibility of setting the host functions, although the lack of
      appropriate genome engineering tools has unpaved it. Fortunately, the emergence
      of genome editing technologies based on programmable nucleases, and especially
      the arrival of a multipurpose RNA-guided Cas9 endonuclease system, has made it
      possible to reconsider this challenge. For such purpose, a particular type of
      transposons referred to as miniature inverted-repeat transposable elements
      (MITEs) has shown a series of interesting characteristics for designing
      functional drivers. Here, recent insights into MITE elements and versatile RNA
      guided CRISPR/Cas9 genome engineering system are given to understand how to
      deploy the potential of TEs for control of the host transcriptional activity.

PMID- 29032446
TI  - Homogenization analysis of invasion dynamics in heterogeneous landscapes with
      differential bias and motility.
AB  - Animal movement behaviors vary spatially in response to environmental
      heterogeneity. An important problem in spatial ecology is to determine how large
      scale population growth and dispersal patterns emerge within highly variable
      landscapes. We apply the method of homogenization to study the large-scale
      behavior of a reaction-diffusion-advection model of population growth and
      dispersal. Our model includes small-scale variation in the directed and random
      components of movement and growth rates, as well as large-scale drift. Using the
      homogenized model we derive simple approximate formulas for persistence
      conditions and asymptotic invasion speeds, which are interpreted in terms of
      residence index. The homogenization results show good agreement with numerical
      solutions for environments with a high degree of fragmentation, both with and
      without periodicity at the fast scale. The simplicity of the formulas, and their
      connection to residence index make them appealing for studying the large-scale
      effects of a variety of small-scale movement behaviors.

PMID- 29032447
TI  - Evaluation and calibration of high-throughput predictions of chemical
      distribution to tissues.
AB  - Toxicokinetics (TK) provides critical information for integrating chemical
      toxicity and exposure assessments in order to determine potential chemical risk
      (i.e., the margin between toxic doses and plausible exposures). For thousands of
      chemicals that are present in our environment, in vivo TK data are lacking. The
      publicly available R package "httk" (version 1.8, named for "high throughput TK")
      draws from a database of in vitro data and physico-chemical properties in order
      to run physiologically-based TK (PBTK) models for 553 compounds. The PBTK model
      parameters include tissue:plasma partition coefficients (Kp) which the httk
      software predicts using the model of Schmitt (Toxicol In Vitro 22 (2):457-467,
      2008). In this paper we evaluated and modified httk predictions, and quantified
      confidence using in vivo literature data. We used 964 rat Kp measured by in vivo
      experiments for 143 compounds. Initially, predicted Kp were significantly larger
      than measured Kp for many lipophilic compounds (log10 octanol:water partition
      coefficient > 3). Hence the approach for predicting Kp was revised to account for
      possible deficiencies in the in vitro protein binding assay, and the method for
      predicting membrane affinity was revised. These changes yielded improvements
      ranging from a factor of 10 to nearly a factor of 10,000 for 83 Kp across 23
      compounds with only 3 Kp worsening by more than a factor of 10. The vast majority
      (92%) of Kp were predicted within a factor of 10 of the measured value (overall
      root mean squared error of 0.59 on log10-transformed scale). After applying the
      adjustments, regressions were performed to calibrate and evaluate the predictions
      for 12 tissues. Predictions for some tissues (e.g., spleen, bone, gut, lung) were
      observed to be better than predictions for other tissues (e.g., skin, brain,
      fat), indicating that confidence in the application of in silico tools to predict
      chemical partitioning varies depending upon the tissues involved. Our calibrated
      model was then evaluated using a second data set of human in vivo measurements of
      volume of distribution (Vss) for 498 compounds reviewed by Obach et al. (Drug
      Metab Dispos 36(7):1385-1405, 2008). We found that calibration of the model
      improved performance: a regression of the measured values as a function of the
      predictions has a slope of 1.03, intercept of - 0.04, and R2 of 0.43. Through
      careful evaluation of predictive methods for chemical partitioning into tissues,
      we have improved and calibrated these methods and quantified confidence for TK
      predictions in humans and rats.

PMID- 29032448
TI  - Effect of single-residue bulges on RNA double-helical structures:
      crystallographic database analysis and molecular dynamics simulation studies.
AB  - Asymmetric bulge loop motifs are widely dispersed in all types of functional
      RNAs. They are frequently occurring structural motifs in folded RNA structures
      and appear commonly in pre-microRNA and ribosomes, where they are involved in
      specific RNA-RNA and RNA-protein interactions. It is therefore necessary to
      understand such motifs from a structural point of view. We analyzed all available
      RNA structures and identified quite a few fragments of double helices that
      contain bulges. We found that these discontinuities often introduce kinks into
      the double helices, which also affects the stacking overlap between the base
      pairs across the irregularity. In order to understand the influence of these
      bulges on stability and flexibility, we carried out molecular dynamics
      simulations of three different single-residue bulge-containing RNA helices using
      the CHARMM36 force field. The structural variability at the junctions of RNA
      bulges is expected to differ from that in continuous double-helical stretches.
      The structural features of the junction region were observed to vary noticeably
      depending on the orientation of the bulge residue. When the base of the bulge
      residue is looped out, the RNA stretch behaves like a standard long A-form RNA
      double helix, whereas the entire RNA behaves differently when the base of the
      bulge residue is intercalated between base pairs inside the RNA stem. Such single
      base intercalation was found to introduce a permanent kink into the composite
      double helix, which could be a recognition element for Dicer during the
      maturation of miRNA.

PMID- 29032449
TI  - Effectiveness of a Self Help Cognitive Behavioural Treatment Program for Problem
      Gamblers: A Randomised Controlled Trial.
AB  - The study aimed to strengthen the scarce literature on self-help treatments for
      Problem Gambling (PG) by comparing the effectiveness of a Self-Help Cognitive
      Behavioral Treatment (SHCBT) program (n = 23) with a 6-week Waitlist condition (n
      = 32) in problem gamblers. Participants were community volunteers with gambling
      problems and were randomly allocated to the Waitlist and treatment conditions.
      Results showed significant improvements at post-treatment in gambling behaviors
      including frequency of gambling, average amount gambled per day and PG symptoms
      as well as a number of gambling correlates including psychological states (e.g.,
      depression, anxiety and stress), gambling cognitions, gambling urges, gambling
      related self-efficacy, satisfaction with life, and quality of life among those
      who completed the SHCBT program, when compared with the waitlist condition. The
      effect size (partial eta 2) ranged from .25 to .57 for all assessed outcomes that
      showed significant improvement from pre- to post-treatment. It was concluded that
      a self-help CBT program can be beneficial for treating community problem
      gamblers.

PMID- 29032451
TI  - Impact of body mass index on the oncological outcomes of patients treated with
      radical nephroureterectomy for upper tract urothelial carcinoma.
AB  - PURPOSE: To evaluate the association between body mass index (BMI) and
      oncological outcomes in patients treated with radical nephroureterectomy (RNU)
      for upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively reviewed
      237 consecutive patients treated with RNU for UTUC at our institution between
      1990 and 2012. Univariable and multivariable cox regression models investigated
      the association of BMI with disease recurrence, cancer-specific mortality, and
      overall mortality. RESULTS: From the 237 patients, 104 (44%) had a BMI < 25
      kg/m2, 88 (37%) had a BMI between 25 and 29.9 kg/m2, and 45 (19%) had a BMI >= 30
      kg/m2 at the time of surgery. Within a median follow-up of 44 months (IQR: 24
      79), 53 patients (22.4%) experienced a disease recurrence, 85 patients (35.9%)
      had bladder recurrence, and 44 patients (18.6%) died from the disease. The 5 year
      recurrence-free and cancer-specific survival rates were, respectively, 32 and 56%
      for BMI >= 30 kg/m2, 45 and 74% for patients with BMI 25-29.9 kg/m2, and 69 and
      81% for patients with BMI < 25 kg/m2. In multivariable analyses that adjusted for
      the effects of the standard clinico-pathological features, BMI >= 30 kg/m2 was
      associated with a higher risk of disease recurrence (HR 3.23; 95% CI 2.3-6.6, p <
      0.001) and cancer-specific mortality (HR 3.84; 95% CI 2.8-6.5; p < 0.001).
      CONCLUSIONS: Obesity was independently associated with higher risks of disease
      recurrence and cancer-specific mortality in patients treated with RNU for UTUC.

PMID- 29032450
TI  - Association between coronary artery disease severity and overactive bladder in
      geriatric patients.
AB  - PURPOSE: To investigate the association between overactive bladder (OAB) and
      coronary artery disease (CAD) as demonstrated on coronary angiography in patients
      > 65 years. METHODS: The patients who were > 65 years completed an OAB-V8 form
      before undergoing coronary angiography at a tertiary care hospital. The presence
      of OAB was documented using the self-administered OAB-V8 questionnaire. Formal
      stratification of the coronary vessels plaque burden was assessed by calculation
      of a Gensini score for each patient. Body mass index (BMI) blood urea nitrogen
      (BUN), serum lipid profile, fasting plasma glucose, urinalysis, urine culture,
      uroflowmetry, and postvoiding residual urine volume were measured for each
      patient. RESULTS: A total of 308 patients were analysed. Before coronary
      angiography, the patients were divided into two groups according to the score on
      the OAB-V8 questionnaire. The OAB group (n: 153) comprised those with a score >=
      8 and the non-OAB group (n: 155), those with a score < 8. The mean age of the
      patients was 75.08 +/- 5.01 years in the OAB group and 68.73 +/- 3.26 years in
      the non-OAB group (p < 0.001). The Gensini scores of the patients in the OAB and
      non-OAB groups were 22.48 +/- 3.51 and 5.89 +/- 2.72, respectively (p = 0.001).
      In multiple regression analysis, no significant difference was determined between
      the groups in terms of gender, fasting blood glucose level, presence of
      hypertension, smoking, BMI, and BUN, except LDL and cholesterol levels.
      CONCLUSIONS: In this preliminary investigation, the incidence of severe CAD was
      found to be higher in patients with OAB symptoms.

PMID- 29032452
TI  - Treatment Outcomes with Biosimilars: Be Aware of the Nocebo Effect.
AB  - : Over the years, biologic agents have proven their importance in the management
      of chronic autoimmune diseases, such as rheumatoid arthritis, psoriasis, and
      inflammatory bowel disease. Biosimilars, which are biologic medicines, are highly
      similar to approved biologic medicines, and are comprehensively developed and
      rigorously tested to ensure efficacy and safety are similar to the reference
      product. A broader armamentarium of biosimilars is expected to improve patients'
      access to safe and effective biologic medicines, thus offering benefits to
      healthcare systems around the globe. Here we consider the factors that may
      compromise the benefits of biosimilars being realized, including patient and
      physician perception of biosimilars, and an often overlooked factor, the nocebo
      effect, which is re-emerging with the widespread adoption of biosimilar
      medicines. We have also described a variety of strategies and recommendations
      that could help limit the nocebo effect. FUNDING: Biogen.

PMID- 29032453
TI  - Rapid and sensitive detection of ketamine in blood using novel fluorescence
      genosensor.
AB  - In recent years, drug abuse has been considered as a most challenging social
      problem that aroused public attention. Ketamine has increased in unregulated use
      as a 'recreational drug' in teenagers. However, there is no suitable and
      maneuverable detection method for ketamine in situ at the moment. Fluorescence
      sensor technique, with predominant recognition and simple operation, is a good
      potential application in drug detection. Here, we first reported a highly
      sensitive and selective fluorescence genosensor for rapid detection of ketamine
      based on DNA-templated silver nanoclusters (DNA-AgNCs) probes, in which the DNA
      sequence could specially recognize ketamine with high affinity. Parameters
      affecting detection efficiency were investigated and optimized. Under optimum
      conditions, the as-prepared genosensor can allow for the determination of
      ketamine in the concentration range of 0.0001-20 MUg/mL with two linear
      equations: one is y = 2.84x-7.139 (R2 = 0.987) for 0.0001-0.1 MUg/mL, and the
      other is y = 1.87x-0.091 (R2 = 0.962) for 0.1-20 MUg/mL, and the estimated
      detection limit of ketamine is 0.06 ng/mL. Moreover, the feasibility of this
      proposed method was also demonstrated by analyzing forensic blood samples.
      Compared with official gas chromatography/mass spectrometry (GC/MS), this
      fluorescence genosensor is simple, rapid, and accurate for quantitative
      determination of ketamine in blood for pharmaceutical and forensic analysis.
      Overall, it is the first report on a fluorescence genosensor for detecting
      ketamine directly in blood. This research may provide a new insight for the
      analyst to band fluorescence genosensor technology together with drug monitoring
      in the battle against drug abuse and forensic examination. Graphical abstract
      High selectively detection of ketamine using a novel fluorescence genosensor
      based on DNA-AgNCs probe.

PMID- 29032454
TI  - Multivariate optimization of a microextraction by packed sorbent-programmed
      temperature vaporization-gas chromatography-tandem mass spectrometry method for
      organophosphate flame retardant analysis in environmental aqueous matrices.
AB  - In this work, organophosphate ester flame retardant (OPFRs) assay in
      environmental waters was addressed by using microextraction by packed sorbent
      (MEPS) and gas chromatography-tandem mass spectrometry (GC-MS/MS). Ten OPFRs with
      different physicochemical properties were taken into account as target compounds
      for a comprehensive method evaluation. Five MEPS cartridges (i.e., C2, C8, C18,
      Silica, and DVB) and seven solvents (i.e., methanol, ethyl acetate, methyl tert
      butyl ether, hexane, acetonitrile, dichloromethane, and trichloromethane) were
      surveyed. The analysis was performed by using a gas chromatograph equipped with a
      programmed temperature vaporization injector (PTV). Univariate and multivariate
      approaches were exploited in order to optimize the parameters affecting the MEPS
      extraction and the PTV injection of the analytes into the gas chromatographic
      system. The optimal working conditions were achieved using DVB as sorbent
      material and acetonitrile as elution solvent. Internal standard calibration was
      carried out using TBP-d27 and TCEP-d12. Satisfactory values of accuracy and
      precision were generally obtained as well as limit of detection (2.7-99 pg/mL for
      tap water; 2.9-97 pg/mL for river water; 3-107 pg/mL for wastewater) and limit of
      quantification (0.01-0.2 ng/mL). The proposed protocol was evaluated on real case
      scenarios by analyzing tap water, river water and simulated wastewater samples.
      The developed method is not only eco-friendly due to the low use of organic
      solvents but also simple and automatable since the MEPS extraction procedure can
      be implemented in the autosampler routine. Graphical abstract The steps of the
      analytical protocol.

PMID- 29032455
TI  - Electrochemical aptamer-based biosensor developed to monitor PSA and VEGF
      released by prostate cancer cells.
AB  - Early prostate cancer (PCa) diagnostic is crucial to enhance patient survival
      rates; besides, non-invasive platforms have been developed worldwide in order to
      precisely detect PCa biomarkers. Therefore, the aim of the present study is to
      develop a new aptamer-based biosensor through the self-assembling of thiolated
      aptamers for PSA and VEGF on the top of gold electrodes. This biosensor was
      tested in three prostate cell lines (RWPE-1, LNCaP and PC3). The results
      evidenced a stable and sensitive sensor presenting wide linear detection ranges
      (0.08-100 ng/mL for PSA and 0.15 ng-100 ng/mL for VEGF). Therefore, the
      aptasensor was able to detect the patterns of PSA and VEGF released in vitro by
      PCa cells, which gave new insights about the prostate cancer protein dynamics.
      Thus, it could be used as a non-invasive PCa clinical diagnosis instrument in the
      near future. Graphical Abstract Overview of the experimental design applied to
      the aptamer-based electrochemical sensor self-assembled on the thiolated hairpin
      structure. A filter membrane was added on top of working electrode to provide the
      cell-attachment surface after aptamer incubation, without compromising the
      aptamer layer. The pore membrane allowed target proteins to pass to the aptamer
      surface; the MCH backfilling avoided unspecific protein binding to the gold
      electrode surface.

PMID- 29032456
TI  - Silver-loaded chitosan coating as an integrated approach to face titanium implant
      associated infections: analytical characterization and biological activity.
AB  - The present work focuses on the idea to prevent and/or inhibit the colonization
      of implant surfaces by microbial pathogens responsible for post-operative
      infections, adjusting antimicrobial properties of the implant surface prior to
      its insertion. An antibacterial coating based on chitosan and silver was
      developed by electrodeposition techniques on poly(acrylic acid)-coated titanium
      substrates. When a silver salt was added during the chitosan deposition step, a
      stable and scalable silver incorporation was achieved. The physico-chemical
      composition of the coating was studied by X-ray photoelectron spectroscopy (XPS),
      while atomic force microscopy in intermittent contact mode (ICAFM) was used to
      explore the coating morphology. The amount of silver released from the coating up
      to 21 days was evaluated by inductively coupled plasma mass spectrometry (ICP
      MS). The capability of the proposed coating to interact in vitro with the
      biological environment in terms of compatibility and antibacterial properties was
      assessed using MG-63 osteoblast-like cell line and S. aureus and P. aeruginosa
      strains, respectively. These studies revealed that a coating showing a silver
      surface atomic percentage equal to 0.3% can be effectively used as antibacterial
      system, while providing good viability of osteoblast-like cells after 7 days. The
      antibacterial effectiveness of the prepared coating is mainly driven by a contact
      killing mechanism, although the low concentration of silver released (below 0.1
      ppm up to 21 days) is enough to inhibit bacterial growth, advantaging MG-63 cells
      in the race for the surface.

PMID- 29032457
TI  - Advances in microRNA analysis.
AB  - MicroRNAs (miRNAs) are single-stranded noncoding RNA molecules that act as key
      regulators of mRNA expression and are emerging biomarkers for disease. Their
      small size (18-25 nt) presents challenges to molecular recognition, labeling, and
      signal generation. Recent research activity in this field has aimed at the
      development of methods for miRNA quantification that combine high detectability,
      broad dynamic range, practicality, multiplexity, and low cost for prospective
      applications in diagnostic laboratories. This review article covers the most
      recent advances in microRNA analysis.

PMID- 29032458
TI  - A Systematic Review of Techniques and Sources of Big Data in the Healthcare
      Sector.
AB  - The main objective of this paper is to present a review of existing researches in
      the literature, referring to Big Data sources and techniques in health sector and
      to identify which of these techniques are the most used in the prediction of
      chronic diseases. Academic databases and systems such as IEEE Xplore, Scopus,
      PubMed and Science Direct were searched, considering the date of publication from
      2006 until the present time. Several search criteria were established as
      'techniques' OR 'sources' AND 'Big Data' AND 'medicine' OR 'health', 'techniques'
      AND 'Big Data' AND 'chronic diseases', etc. Selecting the paper considered of
      interest regarding the description of the techniques and sources of Big Data in
      healthcare. It found a total of 110 articles on techniques and sources of Big
      Data on health from which only 32 have been identified as relevant work. Many of
      the articles show the platforms of Big Data, sources, databases used and identify
      the techniques most used in the prediction of chronic diseases. From the review
      of the analyzed research articles, it can be noticed that the sources and
      techniques of Big Data used in the health sector represent a relevant factor in
      terms of effectiveness, since it allows the application of predictive analysis
      techniques in tasks such as: identification of patients at risk of reentry or
      prevention of hospital or chronic diseases infections, obtaining predictive
      models of quality.

PMID- 29032459
TI  - Predictors of silent corticotroph adenoma recurrence; a large retrospective
      single center study and systematic literature review.
AB  - PURPOSE: Silent corticotroph adenomas (SCAs) are clinically silent and non
      secreting, but exhibit positive adrenocorticotropic hormone (ACTH)
      immunostaining. We characterized a single center cohort of SCA patients, compared
      the SCAs to silent gonadotroph adenomas (SGAs), identified predictors of
      recurrence, and reviewed and compared the cohort to previously published SCAs
      cases. METHODS: Retrospective review of SCA and SGA surgically resected patients
      over 10 years and 6 years, respectively. Definitions; SCA-no clinical or
      biochemical evidence of Cushing's syndrome and ACTH positive immunostaining, and
      SGA-steroidogenic factor (SF-1) positive immunostaining. A systematic literature
      search was undertaken using Pubmed and Scopus. RESULTS: Review revealed 814
      pituitary surgeries, 39 (4.8%) were SCAs. Mean follow-up was 6.4 years (range 0.5
      23.8 years). Pre-operative magnetic resonance imaging demonstrated sphenoid
      and/or cavernous sinus invasion in 44%, 33% were > 50% cystic, and 28% had high
      ACTH levels pre-operatively. Compared to SGAs (n = 70), SCAs were of similar size
      and invasiveness (2.5 vs. 2.9 cm, p = 0.2; 44 vs. 41%, p = 0.8, respectively),
      but recurrence rate was higher (36 vs. 10%, p = 0.001) and more patients received
      radiation therapy (18 vs. 3%, p = 0.006). Less cystic tumors (0 vs. 50%, p <
      0.001) and higher pre-operative ACTH levels (54 vs. 28 pg/ml, p = 0.04) were
      predictors of recurrence for SCAs. CONCLUSION: This review is unique; a strict
      definition of SCA was used, and single center SCAs were compared with SGAs and
      with SCAs literature reviewed cases. We show that SCAs are aggressive and
      identify predictors of recurrence. Accurate initial diagnosis, close imaging and
      biochemical follow up are warranted.

PMID- 29032461
TI  - The effect of ribose pre-treatment of cortical bone on gamma-irradiation
      sterilization effectiveness.
AB  - Reconstruction of large skeletal defects is a significant and challenging issue.
      Tissue banks often use gamma-irradiation (15-35 kGy) to sterilize bone
      allografts, which, however, drastically impairs the post-yield mechanical
      properties. In previous studies, we reported the development of a method that
      protects human bone collagen connectivity through ribose crosslinking while still
      undergoing gamma-irradiation. Given these promising results, the next step was to
      determine if the presence of ribose within the bone tissue would interfere with
      the effectiveness of the gamma-irradiation sterilization against bacteria. This
      study had two stages. The aim of the first stage was to assess the protective
      effect of ribose in solution using a Bacillus pumilus spore strip model. The aim
      of the second stage was to assess the protective effect of ribose (R) on spores
      within a human cortical bone model in comparison to conventionally irradiated
      bone (I). Treatment of B. pumilus spore strips with ribose in solution led to
      temperature-dependent effects on spore viability versus spore strips treated with
      PBS alone. Ribose solution at 60  degrees C led to a notable two logs decrease in
      spore count relative to PBS at 60  degrees C. In the human bone model, the number
      of spores in the I and R groups were greatly decreased in comparison to the non
      irradiated N group. No spore colonies were detected in the R group (n = 4)
      whereas two of the four plates of group I formed colonies. This study provides
      evidence that the method of pre-treating bone with ribose crosslinking prior to
      irradiation sterilization, while improving irradiation sterilized bone allograft
      quality, also may improve the effectiveness of the sterilization process.

PMID- 29032460
TI  - The impact of KIR-HLA genotype on hepatitis B virus clearance in Iranian infected
      individuals.
AB  - Killer cell immunoglobulin like receptors (KIRs) have a principal role in
      regulating the effector functions of NK cells, particularly in viral infections.
      The major ligands for KIRs are human leukocyte antigen (HLA) class I molecules.
      The aim of this study is to investigate the possible association of KIR genes,
      their known HLA ligands and compound KIR-HLA genotypes with hepatitis B virus
      (HBV) infection. Our study group consisted of 202 Iranian HBV-infected patients
      (52 spontaneously recovered, 50 asymptomatic carriers, 50 chronic sufferers and
      50with liver cirrhosis) and 100 ethnic-matched healthy control subjects. KIR and
      HLA genotyping was performed by a polymerase chain reaction-sequence-specific
      primer (PCR-SSP). The frequencies of the KIR2DL5A, KIR2DS1, and KIR3DS1 genes
      were significantly elevated in recovered individuals when compared with both
      control and patient groups. Also, KIR2DL5, and KIR3DP1 full were escalated in
      recovered individuals in comparison with patient groups. In addition, HLA-Bw4
      ligand and HLA-A Bw4 were highly frequent in recovered individuals compared with
      healthy controls. Furthermore, the KIR3DS1 + HLA-Bw4, KIR3DS1 + HLA-Bw4 Iso80 ,
      and KIR3DS1 + HLA-A Bw4 genotypes were significantly more common in recovered
      individuals than both healthy control and patient groups. Interestingly, AA
      genotype had less frequency and Bx had higher frequency in recovered individuals
      compared with both healthy control and patient groups. Our findings suggest a
      potential impact of the NK cells' activating phenotype that leads to the HBV
      clearance in infected individuals.

PMID- 29032463
TI  - Kit W-sh Mutation Prevents Cancellous Bone Loss during Calcium Deprivation.
AB  - Calcium is essential for normal bone growth and development. Inadequate calcium
      intake increases the risk of osteoporosis and fractures. Kit ligand/c-Kit
      signaling plays an important role in regulating bone homeostasis. Mice with c-Kit
      mutations are osteopenic. The present study aimed to investigate whether
      impairment of or reduction in c-Kit signaling affects bone turnover during
      calcium deprivation. Three-week-old male WBB6F1/J-Kit W /Kit W-v /J (W/W v ) mice
      with c-Kit point mutation, Kit W-sh /HNihrJaeBsmJ (W sh /W sh ) mice with an
      inversion mutation in the regulatory elements upstream of the c-Kit promoter
      region, and their wild-type controls (WT) were fed either a normal (0.6% calcium)
      or a low calcium diet (0.02% calcium) for 3 weeks. MUCT analysis indicated that
      both mutants fed normal calcium diet had significantly decreased cortical
      thickness and cancellous bone volume compared to WT. The low calcium diet
      resulted in a comparable reduction in cortical bone volume and cortical thickness
      in the W/W v and W sh /W sh mice, and their corresponding controls. As expected,
      the low calcium diet induced cancellous bone loss in the W/W v mice. In contrast,
      W sh /W sh cancellous bone did not respond to this diet. This c-Kit mutation
      prevented cancellous bone loss by antagonizing the low calcium diet-induced
      increase in osteoblast and osteoclast numbers in the W sh /W sh mice. Gene
      expression profiling showed that calcium deficiency increased Osx, Ocn, Alp, type
      I collagen, c-Fms, M-CSF, and RANKL/OPG mRNA expression in controls; however, the
      W sh mutation suppressed these effects. Our findings indicate that although
      calcium restriction increased bone turnover, leading to osteopenia, the decreased
      c-Kit expression levels in the W sh /W sh mice prevented the low calcium diet
      induced increase in cancellous bone turnover and bone loss but not the cortical
      bone loss.

PMID- 29032462
TI  - Association of TNFSF4 Polymorphisms with Neuromyelitis Optica Spectrum Disorders
      in a Chinese Population.
AB  - The tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene encodes a
      vital co-stimulatory molecule of the immune system and has been identified as a
      susceptibility locus for systemic lupus erythematosus, systemic sclerosis, and
      primary Sjogren's syndrome. However, the association of TNFSF4 polymorphisms with
      neuromyelitis optica spectrum disorders (NMOSD), an inflammatory, demyelinating
      autoimmune disease of the central nervous system, has not yet been investigated.
      To evaluate whether TNFSF4 polymorphisms contribute to risk of NMOSD, four single
      nucleotide polymorphisms (SNPs) (rs1234315, rs2205960, rs704840, and rs844648)
      were selected and genotyped in a cohort of 312 patients with NMOSD and 487
      healthy controls. Our study showed that rs844648 was associated with an increased
      risk of NMOSD, according to the allelic model (OR = 1.30, 95% CI 1.06-1.59, P =
      0.011, Pcorr = 0.044). Significant associations of rs844648 (OR = 1.67, 95% CI
      1.17-2.38, P = 0.005, Pcorr = 0.02) and rs704840 (OR = 1.75, 95% CI 1.17-2.63, P
      = 0.007, Pcorr = 0.027) with NMOSD occurrence were also observed under the
      recessive model. Moreover, linkage disequilibrium analysis revealed two blocks
      within TNFSF4; in one block, the haplotype Ars844648Grs704840 significantly
      increased the risk of NMOSD, whereas Grs844648Trs704840 reduced the risk. This
      study demonstrates an association between TNFSF4 polymorphisms and susceptibility
      for the development of NMOSD in the Chinese population.

PMID- 29032465
TI  - Hypoxia and hypoxia-inducible factors in neuroblastoma.
AB  - Hypoxia (i.e., low oxygen levels) is a known feature of aggressive tumors. Cells,
      including tumor cells, respond to conditions of insufficient oxygen by activating
      a transcriptional program mainly driven by hypoxia-inducible factors (HIF)-1 and
      HIF-2. Both HIF-1alpha and HIF-2alpha expression levels have been shown to
      correlate to patient outcome in various tumor forms and in neuroblastoma, a solid
      childhood tumor of the sympathetic nervous system, in particular, HIF-2alpha
      marks a subpopulation of immature neural crest-like perivascularly located cells
      and associates with aggressive disease and distant metastasis. It has for long
      been recognized that the HIF-alpha subunits are oxygen-dependently regulated at
      the post-translational level, via ubiquitination and proteasomal degradation.
      Evidence of oxygen-independent mechanisms of regulation, transcriptional control
      of EPAS1/HIF2A and possible cytoplasmic activities of HIF-2alpha has also emerged
      during recent years. In this review, we discuss these non-conventional actions of
      HIF-2alpha, its putative role as a therapeutic target and the constraints it
      carries, as well as the importance of HIF-2 activity in a vascularized setting,
      the so-called pseudo-hypoxic state.

PMID- 29032464
TI  - Nutritional composition of honey bee food stores vary with floral composition.
AB  - Sufficiently diverse and abundant resources are essential for generalist
      consumers, and form an important part of a suite of conservation strategies for
      pollinators. Honey bees are generalist foragers and are dependent on diverse
      forage to adequately meet their nutritional needs. Through analysis of stored
      pollen (bee bread) samples obtained from 26 honey bee (Apis mellifera L.) hives
      across NW-England, we quantified bee bread nutritional content and the plant
      species that produced these stores from pollen. Protein was the most abundant
      nutrient by mass (63%), followed by carbohydrates (26%). Protein and lipid
      content (but not carbohydrate) contributed significantly to ordinations of floral
      diversity, linking dietary quality with forage composition. DNA sequencing of the
      ITS2 region of the nuclear ribosomal DNA gene identified pollen from 89 distinct
      plant genera, with each bee bread sample containing between 6 and 35 pollen
      types. Dominant genera included dandelion (Taraxacum), which was positively
      correlated with bee bread protein content, and cherry (Prunus), which was
      negatively correlated with the amount of protein. In addition, proportions of
      amino acids (e.g. histidine and valine) varied as a function of floral species
      composition. These results also quantify the effects of individual plant genera
      on the nutrition of honey bees. We conclude that pollens of different plants act
      synergistically to influence host nutrition; the pollen diversity of bee bread is
      linked to its nutrient content. Diverse environments compensate for the loss of
      individual forage plants, and diversity loss may, therefore, destabilize consumer
      communities due to restricted access to alternative resources.

PMID- 29032466
TI  - Codon usage and amino acid usage influence genes expression level.
AB  - Highly expressed genes in any species differ in the usage frequency of synonymous
      codons. The relative recurrence of an event of the favored codon pair (amino acid
      pairs) varies between gene and genomes due to varying gene expression and
      different base composition. Here we propose a new measure for predicting the gene
      expression level, i.e., codon plus amino bias index (CABI). Our approach is based
      on the relative bias of the favored codon pair inclination among the genes,
      illustrated by analyzing the CABI score of the Medicago truncatula genes. CABI
      showed strong correlation with all other widely used measures (CAI, RCBS, SCUO)
      for gene expression analysis. Surprisingly, CABI outperforms all other measures
      by showing better correlation with the wet-lab data. This emphasizes the
      importance of the neighboring codons of the favored codon in a synonymous group
      while estimating the expression level of a gene.

PMID- 29032468
TI  - The M2 haplotype of ANXA5 gene in the context of unexplained recurrent
      miscarriages.

PMID- 29032467
TI  - A Helicobacter pylori Vacuolating Cytotoxin A: Mouse DHFR Fusion Protein Triggers
      Dye Release from Liposomes.
AB  - The membrane perturbing action of the VacA toxin from Helicobacter pylori is
      responsible for vacuole formation in intracellular compartments and the induction
      of apoptosis. The VacA toxin contains 2 major domains, p33 and p55, which are
      involved in receptor binding and membrane pore formation, respectively. Improved
      methodologies for VacA purification and assays are urgently needed for further
      detailed investigations on the mechanism of action of this significant virulence
      factor. We found that by fusing mouse DHFR with the N-terminus of the full-length
      (p88) VacA toxin, expression levels in recombinant E. coli were substantially
      increased when compared to the conventional (His)6-tagged protein. The DHFR-VacA
      fusion protein was active in sulforhodamine dye-release assays using liposomes at
      acidic pH in a concentration-dependent manner. Enzymatic activity of DHFR in the
      fusion protein was comparable to a commercial reference sample of purified DHFR;
      however, activity was insensitive to inhibition by methotrexate. Our findings
      suggest that the VacA p88 toxin with a modified N-terminus still maintains its
      capability for membrane insertion and that pH-dependent conformational changes
      occur during interaction of VacA with membranes.

PMID- 29032469
TI  - iTRAQ-based proteomic profiling of a Microbacterium sp. strain during
      benzo(a)pyrene removal under anaerobic conditions.
AB  - This study focused on the protein expression of a Microbacterium sp. strain that
      utilized various concentrations of benzo(a)pyrene (BaP) as the sole source of
      carbon and energy under anaerobic conditions. A total of 1539 protein species
      were quantified by isobaric tags for relative and absolute quantitation (iTRAQ)
      coupled with LC-MS/MS. GO, COG, and pathway enrichment analysis showed that most
      proteins demonstrated catalytic and binding functions and were mainly involved in
      metabolic processes, cellular processes, and single-organism processes. Sixty-two
      proteins were found in their abundances in BaP-stress conditions different from
      normal conditions. These proteins function in the metabolic pathways; the
      biosynthesis of secondary metabolites, the biosynthesis of antibiotics, microbial
      metabolism in diverse environments, carbon metabolism, and the biosynthesis of
      amino acids were markedly altered. Furthermore, enoyl-CoA hydratase was proposed
      to be a key protein during BaP removal of the Microbacterium sp. strain. This
      study provides a powerful platform for the further exploration of BaP removal,
      and the differentially expressed proteins provide insight into the mechanism of
      the BaP removal pathway.

PMID- 29032470
TI  - Growth and biomass productivity of Scenedesmus vacuolatus on a twin layer system
      and a comparison with other types of cultivations.
AB  - Scenedesmus is a genus of microalgae employed for several industrial uses.
      Industrial cultivations are performed in open ponds or in closed photobioreactors
      (PBRs). In the last years, a novel type of PBR based on immobilized microalgae
      has been developed termed porous substrate photobioreactors (PSBR) to achieve
      significant higher biomass density during cultivation in comparison to classical
      PBRs. This work presents a study of the growth of Scenedesmus vacuolatus in a
      Twin Layer System PSBR at different light intensities (600 MUmol photons m-2 s-1
      or 1000 MUmol photons m-2 s-1), different types and concentrations of the
      nitrogen sources (nitrate or urea), and at two CO2 levels in the gas phase (2% or
      0.04% v/v). The microalgal growth was followed by monitoring the attached biomass
      density as dry weight, the specific growth rate and pigment accumulation. The
      highest productivity (29 g m-2 d-1) was observed at a light intensity of 600
      MUmol photons m-2 s-1 and 2% CO2. The types and concentrations of nitrogen
      sources did not influence the biomass productivity. Instead, the higher light
      intensity of 1000 MUmol photons m-2 s-1 and an ambient CO2 concentration (0.04%)
      resulted in a significant decrease of productivity to 18 and 10-12 g m-2 d-1,
      respectively. When compared to the performance of similar cultivation systems (15
      30 g m-2 d-1), these results indicate that the Twin Layer cultivation System is a
      competitive technique for intensified microalgal cultivation in terms of
      productivity and, at the same time, biomass density.

PMID- 29032471
TI  - Copper and cerium-regulated gene expression in Methylosinus trichosporium OB3b.
AB  - In aerobic methanotrophs, copper and cerium control the expression and activity
      of different forms of methane monooxygenase and methanol dehydrogenase,
      respectively. To exploit methanotrophy for the valorization of methane, it is
      crucial to determine if these metals exert more global control on gene expression
      in methanotrophs. Using RNA-Seq analysis we compared the transcriptome of
      Methylosinus trichosporium OB3b grown in the presence of varying amounts of
      copper and cerium. When copper was added in the absence of cerium, expression of
      genes encoding for both soluble and particulate methane monooxygenases varied as
      expected. Genes encoding for copper uptake, storage, and efflux also increased,
      indicating that methanotrophs must carefully control copper homeostasis. When
      cerium was added in the absence of copper, expression of genes encoding for
      alternative methanol dehydrogenases varied as expected, but few other genes were
      found to have differential expression. When cerium concentrations were varied in
      the presence of copper, few genes were found to be either up- or downregulated,
      indicating that copper over rules any regulation by cerium. When copper was
      increased in the presence of cerium, however, many genes were upregulated, most
      notably multiple steps of the central methane oxidation pathway, the serine
      cycle, and the ethylmalonyl-CoA pathway. Many genes were also downregulated,
      including those encoding for nitrogenase and hydrogenase. Collectively, these
      data suggest that copper plays a larger role in regulating gene expression in
      methanotrophs, but that significant changes occur when both copper and cerium are
      present.

PMID- 29032472
TI  - Application of proteotyping Strain SolutionTM ver. 2 software and theoretically
      calculated mass database in MALDI-TOF MS typing of Salmonella serotype.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS)-based microbial identification is a popular analytical method.
      Strain Solution proteotyping software available for MALDI-TOF MS has great
      potential for the precise and detailed discrimination of microorganisms at
      serotype- or strain-level, beyond the conventional mass fingerprinting
      approaches. Here, we constructed a theoretically calculated mass database of
      Salmonella enterica subspecies enterica consisting of 12 biomarker proteins:
      ribosomal proteins S8, L15, L17, L21, L25, and S7, Mn-cofactor-containing
      superoxide dismutase (SodA), peptidyl-prolyl cis-trans isomerase C (PPIase C),
      and protein Gns, and uncharacterized proteins YibT, YaiA, and YciF, that can
      allow serotyping of Salmonella. Strain Solution ver. 2 software with the novel
      database constructed in this study demonstrated that 109 strains (94%), including
      the major outbreak-associated serotypes, Enteritidis, Typhimurium, and Infantis,
      could be correctly identified from others by colony-directed MALDI-TOF MS using
      116 strains belonging to 23 kinds of typed and untyped serotypes of S. enterica
      from culture collections, patients, and foods. We conclude that Strain Solution
      ver. 2 software integrated with the accurate mass database will be useful for the
      bacterial proteotyping by MALDI-TOF MS-based microbial classification in the
      clinical and food safety fields.

PMID- 29032473
TI  - Oligosaccharide biotechnology: an approach of prebiotic revolution on the
      industry.
AB  - Oligosaccharides are polymers with two to ten monosaccharide residues which have
      sweetener functions and sensory characteristics, in addition to exerting
      physiological effects on human health. The ones called nondigestible exhibit a
      prebiotic behavior being fermented by colonic microflora or stimulating the
      growth of beneficial bacteria, playing roles in the immune system, protecting
      against cancer, and preventing cardiovascular and metabolic issues. The global
      prebiotics market is expected to grow around 12.7% in the next 8 years, so
      manufacturers are developing new alternatives to obtain sustainable and efficient
      processes for application on a large scale. Most studied examples of
      biotechnological processes involve the development of new strategies for
      fructooligosaccharide, galactooligosaccharide, xylooligosaccharide, and
      mannanooligosaccharide synthesis. Among these, the use of whole cells in
      fermentation, synthesis of microbial enzymes (beta-fructofuranosidases, beta
      galactosidases, xylanases, and beta-mannanases), and enzymatic process
      development (permeabilization, immobilization, gene expression) can be
      highlighted, especially if the production costs are reduced by the use of agro
      industrial residues or by-products such as molasses, milk whey, cotton stalks,
      corncobs, wheat straw, poplar wood, sugarcane bagasse, and copra meal. This
      review comprises recent studies to demonstrate the potential for biotechnological
      production of oligosaccharides, and also aspects that need more investigation for
      future applications in a large scale.

PMID- 29032474
TI  - Discrepancy between the initial assessment of injury severity and post hoc
      determination of injury severity in patients with apparently mild traumatic brain
      injury: a retrospective multicenter cohort analysis.
AB  - PURPOSE: Traumatic brain injury (TBI) is a major cause of trauma-related visits
      to emergency departments (ED). Determination of monitoring requirements of
      patients with apparently mild TBI is challenging. Patients may turn out to be
      more severely injured than initially assumed, and failure to identify these
      patients constitutes a serious threat to patient safety. We, therefore, aimed to
      identify clinical risk factors for more severe injuries in patients with
      apparently mild TBI. METHODS: In a retrospective cohort analysis performed at two
      level I trauma centers, 808 patients aged >= 16 presenting to the ED with head
      trauma and a Glasgow Coma Scale (GCS) score 13-15 who received a head CT scan
      were studied. Discrepancies between the initial TBI severity as determined by GCS
      and severity as determined post hoc by the Head Abbreviated Injury Score were
      assessed. Multiple logistic regression was used to identify risk factors of such
      discrepancies. RESULTS: 104 (12.9%) patients were more severely injured than
      initially classified. A GCS < 15 at presentation (GCS 13: OR 6.2, [95% CI 3.8
      9.9]; GCS 14: OR 2.7, [2.0-3.7]), an SpO2 < 90% (OR 5.4, [1.2-23.4]), loss of
      consciousness (OR 2.3, [1.5-3.5]), absence of equal and reactive pupils (OR 2.1,
      [1.6-2.7]), transport by ambulance (OR 2.0, [1.7-2.4]), and use of anticoagulant
      drugs (OR 1.2, [1.1-1.3]) were independent risk factors of more severe injury.
      CONCLUSIONS: Six risk factors of more severe injury in patients presenting with
      apparently mild TBI were identified. Patients with any of these factors should be
      thoroughly monitored for signs of neurologic deterioration.

PMID- 29032475
TI  - Robot-assisted and conventional freehand pedicle screw placement: a systematic
      review and meta-analysis of randomized controlled trials.
AB  - PURPOSE: Several studies have revealed that robot-assisted technique might
      improve the pedicle screw insertion accuracy, but owing to the limited sample
      sizes in the individual study reported up to now, whether or not robot-assisted
      technique is superior to conventional freehand technique is indefinite. Thus, we
      performed this systematic review and meta-analysis based on randomized controlled
      trials to assess which approach is better. METHODS: Electronic databases
      including PubMed, EMBASE, CENTRAL, ISI Web of Science, CNKI and WanFang were
      systematically searched to identify potentially eligible articles. Main endpoints
      containing the accuracy of pedicle screw implantation and proximal facet joint
      violation were evaluated as risk ratio (RR) and the associated 95% confidence
      intervals (95% CIs), while radiation exposure and surgical duration were
      presented as mean difference (MD) or standard mean difference (SMD). Meta
      analyses were performed using RevMan 5.3 software. RESULTS: Six studies involving
      158 patients (688 pedicle screws) in robot-assisted group and 148 patients (672
      pedicle screws) in freehand group were identified matching our study. The Grade A
      accuracy rate in robot-assisted group was superior to freehand group (RR 1.03,
      95% CI 1.00, 1.06; P = 0.04), but the Grade A + B accuracy rate did not differ
      between the two groups (RR 1.01, 95% CI 0.99, 1.02; P = 0.29). With regard to
      proximal facet joint violation, the combined results suggested that robot
      assisted group was associated with significantly fewer proximal facet joint
      violation than freehand group (RR 0.07, 95% CI 0.01, 0.55; P = 0.01). As was the
      radiation exposure, our findings suggested that robot-assisted technique could
      significantly reduce the intraoperative radiation time (MD - 12.38, 95% CI -
      17.95, - 6.80; P < 0.0001) and radiation dosage (SMD - 0.64, 95% CI - 0.85, -
      0.43; P < 0.00001). But the overall surgical duration was longer in robot
      assisted group than conventional freehand group (MD 20.53, 95% CI 5.17, 35.90; P
      = 0.009). CONCLUSIONS: The robot-assisted technique was associated with
      equivalent accuracy rate of pedicle screw implantation, fewer proximal facet
      joint violation, less intraoperative radiation exposure but longer surgical
      duration than freehand technique. Powerful evidence relies on more randomized
      controlled trials with high quality and larger sample size in the future.

PMID- 29032476
TI  - The 7th Italian supplement: a selection from the Italian Spine Society and
      Scoliosis Study Group (SICV&GIS).

PMID- 29032477
TI  - Comments on mortality and cardiorespiratory complications in trochanteric femoral
      fractures: a ten year retrospective analysis.

PMID- 29032478
TI  - Total knee arthroplasty in patients with a history of illicit intravenous drug
      abuse.
AB  - PURPOSE: Injection drug users are at high risk for both infection with blood
      borne pathogens, namely, human immune deficiency virus (HIV), hepatitis-B, -C
      virus, various bacterial infections, as well as early primary and secondary joint
      degeneration. When total knee arthroplasty (TKA) is anticipated the risk of
      septic complications is a major concern. The purpose of this study was to assess
      the clinical and radiographic outcome of patients with a history of intravenous
      drug use after total knee arthroplasty. The primary outcome was revision rate.
      Secondary outcomes were the Western Ontario and McMaster Universities Arthritis
      Index (WOMAC), Knee Society Score (KSS) and radiographic loosening. METHODS: We
      retrospectively reviewed the records of 1,692 TKA performed or revised in our
      institution. Data of 18 TKA in 12 patients (11 male, 1 female; average age 42,
      range 23-62 years) with a history of intravenous opioid abuse were available for
      final analysis. RESULTS: The mean follow up was 125 (range 25-238) months. Seven
      patients required revision surgery due to periprosthetic joint infection after 62
      months (range 5-159): one two staged revision, three arthrodesis and three
      amputations. The median prosthesis survival was 101 (95%-CI 48-154) months.
      CONCLUSION: Total knee arthroplasty in patients with a history of intravenous
      drug abuse is associated with major complications, including above-the-knee
      amputation. If permanent abstinence from intravenous drug abuse is doubtful,
      other therapeutic options including primary arthrodesis should be considered.

PMID- 29032480
TI  - Correction to: Parents' Translations of Child Gesture Facilitate Word Learning in
      Children with Autism, Down Syndrome and Typical Development.
AB  - The original version of the article unfortunately contained mistake in the
      "Methods/Participants" section (p. 224) as "[M TD = 168.26 (SD = 125.18) vs. M AU
      = 172.91 (SD = 195.88) vs. M DS = 145.43 (SD = 88.78); Kruskal-Wallis, chi 2(2) =
      2.42, p = .30], and for word types [M TD = 28.43 (SD = 26.89) vs. M AU = 39.65
      (SD = 49.07) vs. M DS = 18.35 (SD = 22.78); chi 2(2) = 3.15, p = .21]''. The
      correct text is given below: "[M TD = 51.91 (SD = 59.68) vs. M AU = 74.43 (SD =
      116.01) vs. M DS = 25.26 (SD = 39.39); Kruskal-Wallis, chi 2(2) = 3.39, p = .18],
      and for word types [M TD = 18.48 (SD = 20.51) vs. M AU = 24.74 (SD = 32.98) vs. M
      DS  = 11.22 (SD = 18.87); chi 2(2) = 3.58, p = .17]"..

PMID- 29032479
TI  - "Pulmonary Vein Sign" for Pulmonary Embolism Diagnosis in Computed Tomography
      Angiography.
AB  - PURPOSES: Considering that pulmonary arterial obstruction decreases venous flow,
      we hypothesized that filling defects in pulmonary veins can be identified in
      areas adjacent to pulmonary embolism (PE). This sign was named the "pulmonary
      vein sign" (PVS), and we evaluated its prevalence and performance for PE
      diagnosis in computed tomography pulmonary angiography (CTPA). METHODS: This
      retrospective study enrolled consecutive patients with clinical suspicion of PE
      who underwent CTPA scan. The PVS was defined by the following criteria: (a)
      presence of a homogeneous filling defect of at least 2 cm in a pulmonary vein;
      (b) attenuation of the left atrium > 160 Hounsfield units. Using the cases that
      presented PE on CTPA as reference, sensitivity, specificity, and positive and
      negative predictive values were calculated for PVS. RESULTS: In total, 119
      patients (73 female; mean age, 62 years) were included in this study. PE was
      diagnosed in 44 (35.8%) patients. The PVS was present in 16 out of 44 patients
      with PE. Sensitivity was 36.36% (95% confidence interval (CI) 22.83-52.26%);
      specificity, 98.67% (95% CI 91.79-99.93%); positive predictive value, 94.12% (95%
      CI 69.24-99.69%); negative predictive value, 72.55% (95% CI 62.67-80.70%). The
      Kappa index for the PVS was good (0.801; 95% CI 0.645-0.957). PVS was correlated
      with lobar and segmental pulmonary embolism (p < 0.01). CONCLUSION: Despite a low
      sensitivity, presence of the pulmonary vein sign was highly specific for PE, with
      a good agreement between readers. This sign could contribute for PE diagnosis on
      CTPA studies.

PMID- 29032482
TI  - The use of budget impact analysis in the economic evaluation of new medicines in
      Australia, England, France and the United States: relationship to cost
      effectiveness analysis and methodological challenges.

PMID- 29032481
TI  - Transitioning Together: A Multi-family Group Psychoeducation Program for
      Adolescents with ASD and Their Parents.
AB  - Currently there are few evidence-based programs available for families of
      individuals with ASD during the transition to adulthood. The present study
      provided a preliminary evaluation of a multi-family group psychoeducation
      intervention using a randomized waitlist control design (n = 41). Families in the
      intervention condition participated in Transitioning Together, an 8-week program
      designed to reduce family distress and improve social functioning for
      adolescents. Findings indicated significant improvements in parental depressive
      symptoms and problem solving from pre- to post-intervention for parents in the
      intervention condition but not for parents in the control condition. Social
      interactions also improved for youth in the intervention condition relative to
      controls. Parents reported satisfaction with the program and particularly valued
      the opportunity to interact with other families.

PMID- 29032483
TI  - Regulation of Cardiac Voltage-Gated Sodium Channel by Kinases: Roles of Protein
      Kinases A and C.
AB  - In the heart, voltage-gated sodium (Nav) channel (Nav1.5) is defined by its pore
      forming alpha-subunit and its auxiliary beta-subunits, both of which are
      important for its critical contribution to the initiation and maintenance of the
      cardiac action potential (AP) that underlie normal heart rhythm. The
      physiological relevance of Nav1.5 is further marked by the fact that inherited or
      congenital mutations in Nav1.5 channel gene SCN5A lead to altered functional
      expression (including expression, trafficking, and current density), and are
      generally manifested in the form of distinct cardiac arrhythmic events, epilepsy,
      neuropathic pain, migraine, and neuromuscular disorders. However, despite
      significant advances in defining the pathophysiology of Nav1.5, the molecular
      mechanisms that underlie its regulation and contribution to cardiac disorders are
      poorly understood. It is rapidly becoming evident that the functional expression
      (localization, trafficking and gating) of Nav1.5 may be under modulation by post
      translational modifications that are associated with phosphorylation. We review
      here the molecular basis of cardiac Na channel regulation by kinases (PKA and
      PKC) and the resulting functional consequences. Specifically, we discuss: (1)
      recent literature on the structural, molecular, and functional properties of
      cardiac Nav1.5 channels; (2) how these properties may be altered by
      phosphorylation in disease states underlain by congenital mutations in Nav1.5
      channel and/or subunits such as long QT and Brugada syndromes. Our expectation is
      that understanding the roles of these distinct and complex phosphorylation
      processes on the functional expression of Nav1.5 is likely to provide crucial
      mechanistic insights into Na channel associated arrhythmogenic events and will
      facilitate the development of novel therapeutic strategies.

PMID- 29032485
TI  - Endoscopic plantar fascia release via a suprafascial approach is effective for
      intractable plantar fasciitis.
AB  - PURPOSE: To evaluate the medium-term clinical results of endoscopic plantar
      fascia release (EPFR) using a suprafascial approach for recalcitrant plantar
      fasciitis. METHODS: Twenty-four feet of twenty-three patients who underwent EPFR
      using a suprafascial approach were followed up for more than 2 years using the
      American Orthopedic Foot and Ankle Society (AOFAS) score. The AOFAS score at
      final follow-up was compared between patients who participated in athletic
      activity (group A) and those who were sedentary (group S) and between those with
      and those without calcaneal spur (group with CS and group without CS,
      respectively). The ability of patients to return to athletic activity, and if so,
      the time interval between surgery and return to athletic activity, were
      investigated in group A. Complications were recorded. RESULTS: The median follow
      up duration was 48 months. The mean AOFAS score in all patients increased
      significantly between before surgery and final follow-up (P < 0.001). The mean
      score in group A at final follow-up was significantly higher than that in group S
      (P < 0.05). However, there was no significant difference in the mean score at
      final follow-up between the groups with and without CS. In group A, all patients
      could return to athletic activity after a median 8 weeks. Injury to the first
      branch of the lateral plantar nerve occurred in three feet. CONCLUSION: EPFR
      using a suprafascial approach was effective for recalcitrant plantar fasciitis.
      However, the prognosis of sedentary patients was inferior to that of patients
      engaged in athletic activity. LEVEL OF EVIDENCE: IV.

PMID- 29032484
TI  - Young athletes return too early to knee-strenuous sport, without acceptable knee
      function after anterior cruciate ligament reconstruction.
AB  - PURPOSE: The purpose of this study was to evaluate the return to knee-strenuous
      sport rate, muscle function and subjective knee function among adolescent
      patients (15-20 years of age) and adult patients (21-30 years of age) 8 and 12
      months, respectively, after anterior cruciate ligament (ACL) reconstruction. It
      was hypothesised that no differences in outcome would be found between age groups
      at 8 or 12 months after ACL reconstruction. METHODS: Cross-sectional data from
      five tests of muscle function, from the Knee injury and Osteoarthritis Outcome
      Score (KOOS) and the Tegner Activity Scale (Tegner), performed at 8 and 12 months
      after a primary ACL reconstruction, were extracted from a rehabilitation outcome
      register. A total of 270 (51% women) athletes, aged 15-30 years, who were all
      involved in knee-strenuous sport prior the injury, were included at 8 months
      after ACL reconstruction. At 12 months 203 (51% women) were included. The return
      to knee-strenuous-sport rates and the rate of achieving a limb symmetry index of
      >= 90% in all five tests of muscle function, defined as recovery of muscle
      function, and subjective knee function scores, as measured with the KOOS, were
      compared between age groups. RESULTS: The adolescent patients had a higher (50%)
      return to knee-strenuous sport rate compared with the adult patients (38%) 8
      months after ACL reconstruction (p = 0.04). At the 12-month follow-up, no
      difference was found between the age groups; 74 and 63%, respectively. At the 8
      month follow-up, 29% of the patients, in both age groups, who had returned to
      sport had recovered their muscle function in all five tests of muscle function.
      At the 12-month follow-up, the corresponding results were 20% for the adolescents
      and 28% for the adult patients. No difference in mean KOOS scores was found
      between the age groups at 8 or at 12 months after ACL reconstruction. CONCLUSION:
      The majority of young athletes make an early return to knee-strenuous sport after
      a primary ACL reconstruction, without recovering their muscle function. To set
      realistic expectations, clinicians are recommended to ensure that young athletes
      receive information about not to return before muscle function is recovered and
      that this may take longer time than 12 months. LEVEL OF EVIDENCE: II.

PMID- 29032486
TI  - Population Pharmacokinetics of Subcutaneous Pasireotide in Healthy Volunteers and
      Cushing's Disease Patients.
AB  - BACKGROUND AND OBJECTIVE: Pasireotide (SOM230, Signifor(r)) is a somatostatin
      analog approved in a subcutaneous formulation for the treatment of Cushing's
      disease. This analysis characterizes the population pharmacokinetics (PopPK) of
      subcutaneous pasireotide jointly in healthy volunteers (HVs) and Cushing's
      disease patients (CDPs), evaluating the effects of age, body size, and population
      on pasireotide pharmacokinetics. METHODS: The analysis dataset included five
      phase I studies and one each from phase II and phase III. A three-compartment,
      linear structural pharmacokinetic model was used. Models were specified a priori
      that varied in the relationship between HVs and CDPs, and the model with the
      lowest value of the Bayes Information Criterion (BIC) was selected. It was then
      used to illustrate various features of pasireotide pharmacokinetics. RESULTS AND
      CONCLUSIONS: In the final model, the estimated values of apparent clearance
      (CL/F), central volume of distribution, and deep peripheral volume of
      distribution of pasireotide in CDP were 59, 43, and 225% those of HVs at the same
      age and body size. Clearance increased with body size and decreased with age
      similarly for CDPs and HVs. The estimated CL/F for a typical CDP (40 years old,
      lean body weight [LBW] 49 kg) was 3.72 L/h, and for a typical HV (29 years old,
      LBW 61 kg) was 7.96 L/h. The model was judged adequate by visual predictive
      checks and diagnostic plots separately for HVs and CDPs and can be used for
      simulations for deriving exposure-response metrics for
      pharmacokinetic/pharmacodynamic analyses.

PMID- 29032487
TI  - Pathological and therapeutic roles of innate lymphoid cells in diverse diseases.
AB  - Innate lymphoid cells (ILCs) are a recently defined type of innate-immunity cells
      that belong to the lymphoid lineage and have lymphoid morphology but do not
      express an antigen-specific B cell or T-cell receptor. ILCs regulate immune
      functions prior to the formation of adaptive immunity and exert effector
      functions through a cytokine release. ILCs have been classified into three groups
      according to the transcription factors that regulate their development and
      function and the effector cytokines they produce. Of note, ILCs resemble T helper
      (Th) cells, such as Th1, Th2, and Th17 cells, and show a similar dependence on
      transcription factors and distinct cytokine production. Despite their short
      history in immunology, ILCs have received much attention, and numerous studies
      have revealed biological functions of ILCs including host defense against
      pathogens, inflammation, tissue repair, and metabolic homeostasis. Here, we
      describe recent findings about the roles of ILCs in the pathogenesis of various
      diseases and potential therapeutic targets.

PMID- 29032488
TI  - How Do Individuals Develop Alcohol Use Disorder After Bariatric Surgery? A
      Grounded Theory Exploration.
AB  - BACKGROUND: Bariatric surgery is the most effective treatment for severe obesity.
      However, following Roux-en-Y gastric bypass (RYGB) surgery, a small minority of
      patients develop new-onset alcohol use disorder (AUD), the aetiology of which is
      poorly understood. AIM: The aim is to construct a theory to explain the
      development of AUD among a sample of individuals who reported problematic
      drinking following RYGB. METHOD: Semi-structured interviews were conducted with
      eight RYGB patients diagnosed with AUD attending a multi-disciplinary outpatient
      weight management service at a public hospital in the Republic of Ireland. A
      constructivist grounded theory methodology was used to analyse interview
      transcripts. RESULTS: Participants' main concern was identified as 'unresolved
      psychological issues' which were managed by 'external coping mechanisms', namely,
      'eating to cope'. After RYGB, comfort eating was no longer possible to the same
      extent. Following a 'honeymoon period', participants' need for an external coping
      mechanism resurfaced. 'Filling the void' provides a framework to explain how
      participants managed the symptoms of their unresolved psychological issues
      through 'behavioural substitution', that is, drinking alcohol instead of eating.
      CONCLUSION: The theoretical framework of 'filling the void' adds to contemporary
      research that conceptualises AUD behavioural substitution as 'addiction transfer'
      by describing the process by which the phenomenon occurs as well as the
      characteristics of participants. The clinical implication of this research is to
      advocate for a reshaping of treatment of RYGB patients, with increased
      psychological input following surgery.

PMID- 29032489
TI  - Away from the Islands: Diaspora's Effects on Native Hawaiian Elders and Families
      in California.
AB  - Native Hawaiians, the indigenous people of Hawai'i, were once a healthy and hardy
      people. But today they are affected by varying social and health disparities that
      have led to poor social and health outcomes. Most of the research on Hawaiians in
      general and Native Hawaiian elders in particular has been conducted in Hawai'i,
      even though the Hawaiian Diaspora has resulted in 45% of this population residing
      in North America and Alaska. This qualitative study used key informant interviews
      and focus group methods to examine reasons for migration and perspectives on
      aging and caregiving in a sample of Native Hawaiian elders and family caregivers
      residing in Southern California. Findings identified three general themes:
      discrimination was a factor in their migration from Hawai'i; similarly to non
      Hawaiians, they are concerned about challenges associated with aging and
      caregiving; and Native Hawaiian cultural traditions and values continue to shape
      their caregiving and service preferences.

PMID- 29032490
TI  - Myeloid-Derived Suppressor Cells in the Tumor Microenvironment: Current Knowledge
      and Future Perspectives.
AB  - The current knowledge on tumor-infiltrating myeloid-derived suppressor cells
      (MDSCs) is based mainly on the extensive work performed in murine models. Data
      obtained for human counterparts are generated on the basis of tumor analysis from
      patient samples. Both sources of information led to determination of the main
      suppressive mechanisms used by these cell subsets in tumor-bearing hosts. As a
      result of the identification of protein targets responsible for MDSCs suppressive
      activity, different therapeutics agents have been used to eliminate/reduce their
      adverse effect. In the present work, we review the current knowledge on
      suppressive mechanisms of MDSCs and therapeutic treatments that interfere with
      their differentiation, expansion or activity. Based on the accumulation of new
      evidences supporting their importance for tumor progression and metastasis, the
      interest in these cell types is increasing. We revise the methods of MDSC
      generation/differentiation ex vivo that may help in overcoming problems
      associated with limited numbers of cells available from animals and patients for
      their study.

PMID- 29032491
TI  - Volatiles Emitted by Calling Males of Burying Beetles and Ptomascopus morio
      (Coleoptera: Silphidae: Nicrophorinae) Are Biogenetically Related.
AB  - In burying beetles, Nicrophorus spp. (Coleoptera: Silphidae: Nicrophorinae) mate
      finding is mediated by male produced volatile compounds. To date, pheromone
      components of only two species have been identified. In an attempt to better
      understand the evolution of male pheromone signaling in burying beetles, we
      investigated the male released volatiles of ten Nicrophorus species and one
      closely related nicrophorine species, Ptomascopus mori. Volatiles emitted by
      calling males were collected in the laboratory by means of solid phase micro
      extraction and analyzed using gas chromatography coupled with mass spectrometry.
      Identified volatiles included short chain esters of 4-methylcarboxylic acids,
      terpenoids, and some other aliphatic compounds. The long-range volatile signals
      of the burying beetle species included in this study are blends of two to seven
      components. We found that methyl or ethyl esters of 4-methylheptanoic acid and 4
      methyloctanoic acid are produced by eight of the ten investigated Nicrophorus
      species. These esters may play a key role in chemical communication. Their
      widespread occurrence suggests that these compounds did not evolve recently, but
      appeared relatively early in the phylogeny of the genus. Although Ptomascopus is
      considered the sister genus of Nicrophorus, P. morio males do not produce any of
      the Nicrophorus compounds, but release 3-methylalkan-2-ones, which are absent in
      Nicrophorus. A better understanding of the evolution of burying beetle
      pheromones, however, will only be possible once more species have been studied.

PMID- 29032492
TI  - Stent unzipping using an ultra-high-pressure balloon: in vitro and animal
      experiments.
AB  - As a child grows, limitations to the maximum dilatable stent diameter (MDD) will
      result in stenosis associated with size mismatch. If an implanted stent can be
      intentionally fractured along its length, a process called "unzipping," it may
      eventually be redilated to adult vessel size. Few studies have addressed how a
      stent can be unzipped using an ultra-high-pressure balloon (UHB) with the
      smallest balloon diameter. Eleven commercially available stents, three Liberte
      stents (LS), six genesis renal stents (GS), and two express vascular SD stents
      (ES), were tested for in vitro unzipping. In addition, using eight stents, we
      investigated whether a balloon that had unzipped the stent in vitro would work
      similarly in the vessel of a pig. Finally, we assessed the histological influence
      of the unzipped stent on the surrounding tissue. In a bench test, LS, GS, and ES
      were consistently unzipped by a balloon whose diameter was >= 1.5, 2.18, and 1.66
      times that of MDD, respectively. In animal experiments, LS, GS, and ES were
      predictably unzipped with balloons of 1.50, 1.81, and 1.66 times the MDD,
      respectively. After unzipping, the unzipped strut did not damage the surrounding
      tissue histologically. Use of a UHB enabled unzipping of the stent with a balloon
      diameter less than two times the MDD enables implantation of a larger stent in
      the unzipped small stent by incremental steps.

PMID- 29032493
TI  - Disease-Modifying Therapies for Multiple Sclerosis: A Systematic Literature
      Review of Cost-Effectiveness Studies.
AB  - INTRODUCTION AND OBJECTIVE: Multiple sclerosis (MS) is a chronic inflammatory
      disease of the central nervous system. MS is considered incurable; however,
      disease treatment has advanced significantly over the past several decades with
      the introduction of disease-modifying therapies (DMTs). The current study
      reviewed the cost-effectiveness analyses of DMTs in relapsing-remitting MS (RRMS)
      patients. METHODS: A systematic literature search of bibliographic databases was
      conducted to identify economic evaluations published after 2007. The relevant
      population, intervention, comparators, outcomes, and study design (PICOS) were
      considered. The outcomes of interest were incremental cost-effectiveness ratios
      (ICERs), net monetary benefits, incremental benefits, and incremental costs. The
      Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement
      was used to assess the reporting quality of published studies. RESULTS: A total
      of 1370 potentially relevant citations were identified, of which 33 published
      articles and four Health Technology Assessment (HTA) reports prepared for the UK
      were included in the final analysis. Almost all studies were based on a health
      economic model and considered RRMS as the phase of disease at study entry. The
      studies were conducted in 10 different countries, with approximately 50% based in
      the US. Study outcomes were rarely comparable due to the different settings,
      input data, and assumptions. Even within the same country, the discrepancy
      between study criteria was considerable. The compliance with reporting standards
      of the CHEERS statement was generally high. CONCLUSIONS: Internationally, a large
      number of health economic assessments of DMTs in RRMS were available, yielding
      difficult to compare, and at times conflicting, results.

PMID- 29032494
TI  - The effects of add-on exenatide to insulin on glycemic variability and
      hypoglycemia in patients with type 1 diabetes mellitus.
AB  - OBJECTIVE: To investigate the effect of add-on exenatide to insulin on glycemic
      excursion and the counter-regulatory hormone in response to hypoglycemia in
      patients with type 1 diabetes mellitus (T1DM). METHODS: 30 patients with T1DM
      were recruited and randomly assigned to exenatide + insulin-treated group (group
      1, n = 15) or insulin-only-treated group (group 2, n = 15) for 4 weeks. All
      patients had continuous glucose monitor system (CGMS) applied at before (week-0)
      and after (week-4) treatment to evaluate the glycemic variability. All patients
      had an arginine-stimulated test at before and after treatment. Six patients from
      each group also had hypoglycemic clamp test to assess counter-regulatory hormone
      level. RESULTS: Patients in the exenatide group had significant reductions in
      body weight, body mass index (BMI), total insulin dose, bolus insulin dose,
      fructosamine, and glycemic excursion after 4 weeks' treatment. Compared with
      patients in group 2, the mean amplitude of glycemic excursion (MAGE) and
      coefficient of variation (CV) of exenatide group decreased significantly.
      Similarly, a significant decrease of glucagon (GLC) in the arginine-stimulated
      test was found in group 1. No significant changes of GLC, growth hormone (GH),
      cortisol (COR), epinephrine (E), and norepinephrine (NE) were found in both
      groups during hypoglycemia clamp test. However, patients who had residual islet
      function in group 1 showed an upward trend of basic C-peptide (C-P) and GLC
      during the hypoglycemia period. CONCLUSION: Although exenatide could inhibit
      glucagon secretion during euglycemia or hyperglycemia in patients with T1DM, it
      has no effect on GLC and counter-regulatory hormones during hypoglycemia clamp in
      patients with no functional residual islet test.

PMID- 29032496
TI  - School Practices to Foster LGBT-Supportive Climate: Associations with Adolescent
      Bullying Involvement.
AB  - Lesbian, gay, bisexual, and transgender (LGBT) youth experience disproportionate
      rates of bullying compared to their heterosexual peers. Schools are well
      positioned to address these disparities by creating supportive school climates
      for LGBT youth, but more research is needed to examine the variety of practices
      and professional development opportunities put in place to this end. The current
      study examines how school practices to create supportive LGBT student climate
      relate to student reports of bullying. Student-level data come from the 2013
      Minnesota Student Survey, a state-wide survey of risk and protective factors.
      Ninth and eleventh grade students (N = 31,183) reported on frequency of physical
      and relational bullying victimization and perpetration and sexual orientation
      based harassment. School administrators reported on six practices related to
      creating supportive LGBT school climate (N = 103 schools): having a point person
      for LGBT student issues, displaying sexual orientation-specific content, having a
      gay-straight alliance, discussing bullying based on sexual orientation, and
      providing professional development around LGBT inclusion and LGBT student issues.
      An index was created to indicate how many practices each school used (M = 2.45;
      SD = 1.76). Multilevel logistic regressions indicated that students attending
      schools with more supportive LGBT climates reported lower odds of relational
      bullying victimization, physical bullying perpetration, and sexual orientation
      based harassment compared to students in schools with less supportive LGBT
      climates. Sexual orientation did not moderate these relations, indicating that
      LGBT-supportive practices may be protective for all students, regardless of their
      sexual orientation. Findings support school-wide efforts to create supportive
      climates for LGBQ youth as part of a larger bullying prevention strategy.

PMID- 29032495
TI  - Laparoscopic versus open umbilical or paraumbilical hernia repair: a systematic
      review and meta-analysis.
AB  - OBJECTIVES: To compare outcomes of laparoscopic repair to open repair of
      umbilical and paraumbilical hernias. METHODS: We performed a systematic review in
      accordance with Preferred Reporting Items for Systematic Reviews and Meta
      Analyses statement standards. The review protocol was registered with
      International Prospective Register of Systematic Reviews (Registration Number:
      CRD42016052131). We conducted a search of electronic information sources,
      including MEDLINE; EMBASE; CINAHL; the Cochrane Central Register of Controlled
      Trials (CENTRAL); the World Health Organization International Clinical Trials
      Registry; ClinicalTrials.gov; and ISRCTN Register, and bibliographic reference
      lists to identify all randomised controlled trials (RCTs) and observational
      studies comparing outcomes of laparoscopic repair to open repair of umbilical and
      paraumbilical hernias. We used the Cochrane risk of bias tool and the Newcastle
      Ottawa scale to assess the risk of bias of RCTs and observational studies,
      respectively. Random effects models were applied to calculate pooled outcome
      data. RESULTS: We identified three RCTs and seven retrospective cohort studies,
      enrolling a total of 16,549 patients. Our analyses indicated that open repair was
      associated with a higher risk of wound infection [Odds ratio (OR) 2.35, 95% CI
      1.23-4.48, P = 0.010], wound dehiscence (OR 4.99, 95% CI 1.12-22.28, P = 0.04)
      and recurrence (OR 4.06, 95% CI 1.54-10.71, P = 0.005), longer length of hospital
      stay (MD 26.85, 95% CI 8.15-45.55, P = 0.005) and shorter operative time [Mean
      difference (MD) - 23.07, 95% CI - 36.78 to - 9.35, P = 0.0010] compared to
      laparoscopic repair. There was no difference in the risk of haematoma (OR 2.03,
      95% CI 0.22-18.73, P = 0.53) or seroma (OR 0.67, 95% CI 0.19-2.32, P = 0.53)
      between the two groups. CONCLUSIONS: The best available evidence (randomised and
      non-randomised studies) suggests that laparoscopic repair of umbilical or
      paraumbilical hernias may be associated with a lower risk of wound infection,
      wound dehiscence and recurrence rate, shorter length of stay but longer operative
      time. Results from a limited number of RCTs showed no difference in recurrence
      rates. The quality of the best available evidence is moderate, and selection bias
      is the major concern due to non-randomised design in most of the available
      studies. Therefore, considering the level of available evidence, the most
      reliable approach for repair of umbilical or paraumbilical hernia should be based
      on surgeon's experience, clinical setting, patient's age and size, hernia defect
      size and anatomical characteristics. High quality RCTs are required.

PMID- 29032497
TI  - Emerging mosquito species in Germany-a synopsis after 6 years of mosquito
      monitoring (2011-2016).
AB  - Globalisation and climate change are the main drivers of invasion of non-endemic
      regions by mosquitoes. Mass transportation of people, animals and goods
      facilitate accidental long-distance displacement while climate warming supports
      active spread and establishment of thermophilic species. In the framework of a
      mosquito-monitoring programme, eight non-indigenous culicid species have been
      registered in Germany since 2011, with four of them being more or less efficient
      vectors of disease agents and another four now considered established. The eight
      newly emerged species include Aedes albopictus, Ae. japonicus, Ae. aegypti, Ae.
      koreicus, Ae. berlandi, Ae. pulcritarsis, Anopheles petragnani and Culiseta
      longiareolata. We here review recent findings and at the same time present new
      findings of specimens of non-native mosquito species in Germany.

PMID- 29032498
TI  - Morphological and molecular description of Myxobolus batalhensis n. sp. (Myxozoa,
      Myxosporea), a liver and ovary parasite of Salminus hilarii in Brazil.
AB  - Plasmodia containing myxospores belonging to the genus Myxobolus Butschli, 1882
      were found in the ovaries and liver of Salminus hilarii. Despite its economic
      value, this fish host has no previous reports of myxozoan infections. Herein, we
      describe Myxobolus batalhensis n. sp. using morphological and ultrastructural
      data, as well as histological and SSU rDNA molecular data. The mature myxospores
      were elongated, measuring in average 15.2 +/- 0.8 MUm in length, 8.4 +/- 0.4 MUm
      in width, and 5.1 +/- 0.2 MUm in thickness. Polar capsules were elongated and
      measured 5.3 +/- 0.3 MUm in length and 2.8 +/- 0.3 MUm in width. Polar filaments
      had 6-9 coils. Histopathological analysis showed coagulation necrosis associated
      with cell lysis as a response of the host cell to the parasite in the ovaries. No
      inflammatory reaction was observed in the liver, although the presence of the
      plasmodia caused changes in tissue structure. The phylogenetic analysis of South
      American myxobolid species showed M. batalhensis n. sp. as sister species of
      Myxobolus aureus. This is the first report of a myxozoan species parasitizing S.
      hilarii and the first myxozoan species described in the Batalha river.

PMID- 29032499
TI  - DNA barcoding for molecular identification of Demodex based on mitochondrial
      genes.
AB  - There has been no widely accepted DNA barcode for species identification of
      Demodex. In this study, we attempted to solve this issue. First, mitochondrial
      cox1-5' and 12S gene fragments of Demodex folloculorum, D. brevis, D. canis, and
      D. caprae were amplified, cloned, and sequenced for the first time;
      intra/interspecific divergences were computed and phylogenetic trees were
      reconstructed. Then, divergence frequency distribution plots of those two gene
      fragments were drawn together with mtDNA cox1-middle region and 16S obtained in
      previous studies. Finally, their identification efficiency was evaluated by
      comparing barcoding gap. Results indicated that 12S had the higher identification
      efficiency. Specifically, for cox1-5' region of the four Demodex species,
      intraspecific divergences were less than 2.0%, and interspecific divergences were
      21.1-31.0%; for 12S, intraspecific divergences were less than 1.4%, and
      interspecific divergences were 20.8-26.9%. The phylogenetic trees demonstrated
      that the four Demodex species clustered separately, and divergence frequency
      distribution plot showed that the largest intraspecific divergence of 12S (1.4%)
      was less than cox1-5' region (2.0%), cox1-middle region (3.1%), and 16S (2.8%).
      The barcoding gap of 12S was 19.4%, larger than cox1-5' region (19.1%), cox1
      middle region (11.3%), and 16S (13.0%); the interspecific divergence span of 12S
      was 6.2%, smaller than cox1-5' region (10.0%), cox1-middle region (14.1%), and
      16S (11.4%). Moreover, 12S has a moderate length (517 bp) for sequencing at once.
      Therefore, we proposed mtDNA 12S was more suitable than cox1 and 16S to be a DNA
      barcode for classification and identification of Demodex at lower category level.

PMID- 29032500
TI  - When antibiotic treatment fails.

PMID- 29032501
TI  - Epigenetic regulators: multifunctional proteins modulating hypoxia-inducible
      factor-alpha protein stability and activity.
AB  - The hypoxia-inducible factor (HIF) is a heterodimeric transcription factor
      governing a transcriptional program in response to reduced O2 availability in
      metazoans. It contributes to physiology and pathogenesis of many human diseases
      through its downstream target genes. Emerging studies have shown that the
      transcriptional activity of HIF is highly regulated at multiple levels and the
      epigenetic regulators are essential for HIF-mediated transactivation. In this
      review, we will discuss the comprehensive regulation of HIF transcriptional
      activity by different types of epigenetic regulators.

PMID- 29032505
TI  - Impaired chemosensory control of breathing after depletion of bulbospinal
      catecholaminergic neurons in rats.
AB  - Bulbospinal catecholaminergic neurons located in the rostral aspect of the
      ventrolateral medulla (C1 neurons) or within the ventrolateral pons (A5 neurons)
      are involved in the regulation of blood pressure and sympathetic outflow. A
      stimulus that commonly activates the C1 or A5 neurons is hypoxia, which is also
      involved in breathing activation. Although pharmacological and optogenetic
      evidence suggests that catecholaminergic neurons also regulate breathing, a
      specific contribution of the bulbospinal neurons to respiratory control has not
      been demonstrated. Therefore, in the present study, we evaluated whether the loss
      of bulbospinal catecholaminergic C1 and A5 cells affects cardiorespiratory
      control during resting, hypoxic (8% O2), and hypercapnic (7% CO2) conditions in
      unanesthetized rats. Thoracic spinal cord (T4-T8) injections of the immunotoxin
      anti-dopamine beta-hydroxylase-saporin (anti-DbetaH-SAP-2.4 ng/100 nl) and the
      retrograde tracer Fluor-Gold or ventrolateral pontine injections of 6-OHDA were
      performed in adult male Wistar rats (250-280 g, N = 7-9/group). Anti-DbetaH-SAP
      or 6-OHDA eliminated most bulbospinal C1 and A5 neurons or A5 neurons,
      respectively. Serotonergic neurons and astrocytes were spared. Depletion of the
      bulbospinal catecholaminergic cells did not change cardiorespiratory variables
      under resting condition, but it did affect the response to hypoxia and
      hypercapnia. Specifically, the increase in the ventilation, the number of sighs,
      and the tachycardia were reduced, but the MAP increased during hypoxia in anti
      DbetaH-SAP-treated rats. Our data reveal that the bulbospinal catecholaminergic
      neurons (A5 and C1) facilitate the ventilatory reflex to hypoxia and hypercapnia.

PMID- 29032502
TI  - Gut microbiota changes in the extreme decades of human life: a focus on
      centenarians.
AB  - The gut microbiota (GM) is a complex, evolutionarily molded ecological system,
      which contributes to a variety of physiological functions. The GM is highly
      dynamic, being sensitive to environmental stimuli, and its composition changes
      over the host's entire lifespan. However, the basic question of how much these
      changes may be ascribed to variables such as population, diet, genetics and
      gender, and/or to the aging process per se is still largely unanswered. We argue
      that comparison among studies on centenarians-the best model of healthy aging and
      longevity-recruited from different geographical areas/populations (different
      genetics and dietary habits) can help to disentangle the contribution of aging
      and non-aging-related variables to GM remodeling with age. The current review
      focuses on the role of population, gender and host genetics as possible drivers
      of GM modification along the human aging process. The feedback impact of age
      associated GM variation on the GM-brain axis and GM metabolomics is also
      discussed. We likewise address the role of GM in neurodegenerative diseases such
      as Parkinson's and Alzheimer's, and its possible therapeutic use, taking
      advantage of the fact that centenarians are characterized by an extreme (healthy)
      phenotype versus patients suffering from age-related pathologies. Finally, it is
      argued that longitudinal studies combining metagenomics sequencing and in-depth
      phylogenetic analysis with a comprehensive phenotypic characterization of
      centenarians and patients using up-to-date omics (metabolomics, transcriptomics
      and meta-transcriptomics) are urgently needed.

PMID- 29032504
TI  - Resistance exercise improves cardiac function and mitochondrial efficiency in
      diabetic rat hearts.
AB  - Metabolic disturbance and mitochondrial dysfunction are a hallmark of diabetic
      cardiomyopathy (DC). Resistance exercise (RE) not only enhances the condition of
      healthy individuals but could also improve the status of those with disease.
      However, the beneficial effects of RE in the prevention of DC and mitochondrial
      dysfunction are uncertain. Therefore, this study investigated whether RE
      attenuates DC by improving mitochondrial function using an in vivo rat model of
      diabetes. Fourteen Otsuka Long-Evans Tokushima Fatty rats were assigned to
      sedentary control (SC, n = 7) and RE (n = 7) groups at 28 weeks of age. Long
      Evans Tokushima Otsuka rats were used as the non-diabetic control. The RE rats
      were trained by 20 repetitions of climbing a ladder 5 days per week. RE rats
      exhibited higher glucose uptake and lower lipid profiles, indicating changes in
      energy metabolism. RE rats significantly increased the ejection fraction and
      fractional shortening compared with the SC rats. Isolated mitochondria in RE rats
      showed increase in mitochondrial numbers, which were accompanied by higher
      expression of mitochondrial biogenesis proteins such as proliferator-activated
      receptor-gamma coactivator-1alpha and TFAM. Moreover, RE rats reduced proton
      leakage and reactive oxygen species production, with higher membrane potential.
      These results were accompanied by higher superoxide dismutase 2 and lower
      uncoupling protein 2 (UCP2) and UCP3 levels in RE rats. These data suggest that
      RE is effective at ameliorating DC by improving mitochondrial function, which may
      contribute to the maintenance of diabetic cardiac contractility.

PMID- 29032506
TI  - Differential effects of AMP-activated protein kinase in isolated rat atria
      subjected to simulated ischemia-reperfusion depending on the energetic substrates
      available.
AB  - AMP-activated protein kinase (AMPK) is a serine-threonine kinase that functions
      primarily as a metabolic sensor to coordinate anabolic and catabolic processes in
      the cell, via phosphorylation of multiple proteins involved in metabolic
      pathways, aimed to re-establish energy homeostasis at a cell-autonomous level.
      Myocardial ischemia and reperfusion represents a metabolic stress situation for
      myocytes. Whether AMPK plays a critical role in the metabolic and functional
      responses involved in these conditions remains uncertain. In this study, in order
      to gain a deeper insight into the role of endogenous AMPK activation during
      myocardial ischemia and reperfusion, we explored the effects of the
      pharmacological inhibition of AMPK on contractile function rat, contractile
      reserve, tissue lactate production, tissue ATP content, and cellular viability.
      For this aim, isolated atria subjected to simulated 75 min ischemia-75 min
      reperfusion (Is-Rs) in the presence or absence of the pharmacological inhibitor
      of AMPK (compound C) were used. Since in most clinical situations of ischemia
      reperfusion the heart is exposed to high levels of fatty acids, the influence of
      palmitate present in the incubation medium was also investigated. The present
      results suggest that AMPK activity significantly increases during Is, remaining
      activated during Rs. The results support that intrinsic activation of AMPK has
      functional protective effects in the reperfused atria when glucose is the only
      available energetic substrate whereas it is deleterious when palmitate is also
      available. Cellular viability was not affected by either of these conditions.

PMID- 29032507
TI  - A novel lab-on-a-chip platform for spheroid metabolism monitoring.
AB  - Sensor-based cellular microphysiometry is a technique that allows non-invasive,
      label-free, real-time monitoring of living cells that can greatly improve the
      predictability of toxicology testing by removing the influence of biochemical
      labels. In this work, the Intelligent Mobile Lab for In Vitro Diagnostics (IMOLA
      IVD) was utilized to perform cellular microphysiometry on 3D multicellular
      spheroids. Using a commercial 3D printer, 3 * 3 microwell arrays were fabricated
      to maintain nine previously cultured HepG2 spheroids on a single BioChip.
      Integrated layers above and under the spheroids allowed fluidic contact between
      spheroids in microwells and BioChip sensors while preventing wash out from medium
      perfusion. Spheroid culturing protocols were optimized to grow spheroids to a
      diameter of around 620 MUm prior to transfer onto BioChips. An ON/OFF pump
      cycling protocol was developed to optimize spheroid culture within the designed
      microwells, intermittently perfuse spheroids with fresh culture medium, and
      measure the extracellular acidification rate (EAR) and oxygen uptake rate (OUR)
      with the BioChips of the IMOLA-IVD platform. In a proof-of-concept experiment,
      spheroids were perfused for 36 h with cell culture medium before being exposed to
      medium with 1% sodium dodecyl sulphate (SDS) to lyse cells as a positive control.
      These microphysiometry studies revealed a repeatable pattern of extracellular
      acidification throughout the experiment, indicating the ability to monitor real
      time metabolic activity of spheroids embedded in the newly designed tissue
      encapsulation. After perfusion for 36 h with medium, SDS exposure resulted in an
      instant decrease in EAR and OUR signals from 37 mV/h (+/- 5) to 8 mV/h (+/- 8)
      and from 308 mV/h (+/- 21) to -2 mV/h (+/- 13), respectively. The presented
      spheroid monitoring system holds great potential as a method to automate
      screening and analysis of pharmaceutical agents using 3D multicellular spheroid
      models.

PMID- 29032503
TI  - CD4 and CD8 T lymphocyte interplay in controlling tumor growth.
AB  - The outstanding clinical success of immune checkpoint blockade has revived the
      interest in underlying mechanisms of the immune system that are capable of
      eliminating tumors even in advanced stages. In this scenario, CD4 and CD8 T cell
      responses are part of the cancer immune cycle and both populations significantly
      influence the clinical outcome. In general, the immune system has evolved several
      mechanisms to protect the host against cancer. Each of them has to be undermined
      or evaded during cancer development to enable tumor outgrowth. In this review, we
      give an overview of T lymphocyte-driven control of tumor growth and discuss the
      involved tumor-suppressive mechanisms of the immune system, such as senescence
      surveillance, cancer immunosurveillance, and cancer immunoediting with respect to
      recent clinical developments of immunotherapies. The main focus is on the
      currently existing knowledge about the CD4 and CD8 T lymphocyte interplay that
      mediates the control of tumor growth.

PMID- 29032509
TI  - Systemic trichosporonosis mimicking disseminated varicella zoster viral infection
      during blinatumomab therapy.

PMID- 29032508
TI  - Development and characterization of 2-dimensional culture for buffalo intestinal
      cells.
AB  - Small intestinal epithelial cells (IEC) play a major role in the absorption of
      nutrients and toxins. Due to the similarity of genome-wide single copy protein
      orthologues between cattle and human, establishment of ruminant's primary small
      IEC culture could be a valuable tool for toxicity studies. Therefore, the current
      study focused on the development and characterization of buffalo IEC culture, as
      cattle slaughter is banned in India. The buffalo jejunum fragments were washed
      consecutively several times in saline, warm phosphate buffered saline (PBS), PBS
      with 5 mM dithiothreitol, digesting solution and 2% sorbitol in PBS. The cells
      were cultured on 17 ug/cm2 collagen coated plates and transwell plates with serum
      (2% Fetal bovine serum (FBS) and 10% FBS) and serum-free culture conditions. The
      cells were differentiated into typical epithelial cobblestone morphology from day
      5 onwards in 50% successful cultures. The cultured IEC were characterized by gene
      expression of epithelial cell markers, cytokeratin and vimentin, and enterocyte
      markers like villin, zonula occluden (ZO1), fatty acid binding protein 2 (FABP2)
      and small intestinal peptidase (IP). Based on the morphology and gene expression
      profile, 10% FBS has been recommended for culturing primary buffalo IEC on
      collagen coated plates for 10 days. However, 50% of the successful cultures could
      not show epithelial phenotype on 10% FBS culture conditions even on collagen
      coated plates. Interestingly, undifferentiated IEC showed an increasing
      expression of FABP2, IP and ZO1 transcripts compared to differentiated intestinal
      cells with 10% FBS on collagen plates. Therefore, future studies are needed to
      understand the role of FABP2, IP and ZO1 in differentiation of buffalo IEC.

PMID- 29032510
TI  - Current prognostic and predictive factors in follicular lymphoma.
AB  - Follicular lymphoma (FL) is generally considered an indolent disorder. With
      modern day treatments, long remissions are often achieved both in the front-line
      and relapsed setting. However, a subset of patients has a more aggressive course
      and a worse outcome. Their identification is the main purpose of modern day
      prognostic tools. In this review, we attempt to summarize the evidence concerning
      prognostic and predictive factors in FL, including (1) pre-treatment factors,
      from baseline clinical characteristics and imaging tests to histological grade,
      the microenvironment and genomic abnormalities; (2) post-treatment factors, i.e.,
      depth of response, measured both by imaging tests and minimal residual disease;
      (3) factors at relapse and duration of response; and (4) prognostic factors in
      histological transformation. We conclude that, despite the existence of numerous
      tools, the availability of some of them is still limited; they generally suffer
      from notable downsides, and most have unproven predictive value, thus having
      scarce bearing on the choice of regimen at present. However, with the
      technological and scientific developments of the last few years, the potential
      for these prognostic factors is promising, particularly in combination, which
      will probably, in time, help guide therapeutic decisions.

PMID- 29032511
TI  - Soma Detection in 3D Images of Neurons using Machine Learning Technique.
AB  - Computing and analyzing the neuronal structure is essential to studying
      connectome. Two important tasks for such analysis are finding the soma and
      constructing the neuronal structure. Finding the soma is considered more
      important because it is required for some neuron tracing algorithms. We describe
      a robust automatic soma detection method developed based on the machine learning
      technique. Images of neurons were three-dimensional confocal microscopic images
      in the FlyCircuit database. The testing data were randomly selected raw images
      that contained noises and partial neuronal structures. The number of somas in the
      images was not known in advance. Our method tries to identify all the somas in
      the images. Experimental results showed that the method is efficient and robust.

PMID- 29032513
TI  - Sudden blast phase in chronic myeloid leukemia developed during nilotinib therapy
      after major molecular response was achieved.
AB  - Sudden blast phase (SBP) is a rare event in which patients with chronic myeloid
      leukemia (CML) in complete cytogenetic response (CCyR) rapidly progress to the
      blast phase. Few patients on second-generation tyrosine kinase inhibitors (2nd
      TKIs) have been reported to develop SBP. Here, we report a 45-year-old man
      diagnosed with CML in the chronic phase in April 2008 and immediately started on
      imatinib therapy. He achieved CCyR 12 months after starting imatinib therapy.
      Imatinib was followed by treatment with the 2nd TKIs nilotinib and dasatinib from
      January 2011 to yield a better response. He achieved major molecular response
      (MMR) during dasatinib therapy in February 2012, but did not tolerate dasatinib
      well; hence, he was switched to nilotinib in July 2012. In December 2015, he
      presented at our hospital with fever and lumbago. A complete blood count revealed
      a white blood cell count of 30,500/uL with 60% blasts, leading to diagnosis of
      SBP. After dasatinib therapy and conventional chemotherapy, he again achieved
      MMR. This case demonstrates that SBP may occur after achieving MMR on treatment
      with 2nd TKIs. Continuous careful monitoring is required for the early detection
      of SBP, even in patients who have achieved MMR.

PMID- 29032512
TI  - IL-33 signalling in liver immune cells enhances drug-induced liver injury and
      inflammation.
AB  - OBJECTIVE AND DESIGN: The aim of this study was to investigate the contribution
      of IL-33/ST2 axis in the onset and progression of acute liver injury using a mice
      model of drug-induced liver injury (DILI). MATERIAL AND TREATMENTS: DILI was
      induced by overdose administration of acetaminophen (APAP) by oral gavage in wild
      type BALB/c, ST2-deficient mice and in different bone marrow chimeras.
      Neutrophils were depleted by anti-Ly6G and macrophages with clodronate liposomes
      (CLL). METHODS: Blood and liver were collected for biochemical, immunologic and
      genetic analyses. Mice were imaged by confocal intravital microscopy and liver
      non-parenchymal cells and hepatocytes were isolated for flow cytometry, genetic
      and immunofluorescence studies. RESULTS: Acetaminophen overdose caused a massive
      necrosis and accumulation of immune cells within the liver, concomitantly with IL
      33 and chemokine release. Liver non-parenchymal cells were the major sensors for
      IL-33, and amongst them, neutrophils were the major players in amplification of
      the inflammatory response triggered by IL-33/ST2 signalling pathway. CONCLUSION:
      Blockage of IL-33/ST2 axis reduces APAP-mediated organ injury by dampening liver
      chemokine release and activation of resident and infiltrating liver non
      parenchymal cells.

PMID- 29032514
TI  - Surface roughness and bacterial adhesion on root dentin treated with diode laser
      and conventional desensitizing agents.
AB  - The treatments for dentin hypersensitivity (DH) may change the surface roughness
      of the root dentin, which can lead to biofilm accumulation, increasing the risk
      of root caries. The aim was to compare the surface roughness of root dentin after
      different treatments of DH and the biofilm formation on those surfaces. After
      initial surface roughness (Sa) assessment, 50 bovine root fragments received the
      following treatments (n = 10): G 1-no treatment; G2-5% sodium fluoride varnish;
      G3-professional application of a desensitizing dentifrice; G4-toothbrushing with
      a desensitizing dentifrice; and G5-diode laser application (908 nm; 1.5 W, 20 s).
      The Sa was reevaluated after treatments. Afterward, all samples were incubated in
      a suspension of Streptococcus mutans at 37  degrees C for 24 h. The colony
      forming units (CFU) were counted using a stereoscope, and the results were
      expressed in CFU/mL. The one-way ANOVA and the Tukey's tests compared the
      roughness data and the results obtained on the bacterial adhesion test (alpha =
      5%). G2 (2.3 +/- 1.67%) showed similar Sa variation than G1 (0.25 +/- 0.41%) and
      G5 (5.69 +/- 0.99%), but different from group G3 (9.05 +/- 2.39%). Group 4 showed
      the highest Sa variation (30.02 +/- 3.83%; p < 0.05). Bacterial adhesion was
      higher in G4 (2208 +/- 211.9), suggesting that bacterial growth is greater on
      rougher surfaces. The diode laser and the conventional treatments for DH may
      change the surface roughness of the root dentin, but only brushing with
      desensitizing dentifrice induced a higher bacteria accumulation on root dentin
      surface.

PMID- 29032515
TI  - Oxidative Stress and Heavy Metals in Plants.
AB  - Oxidative stress is a pathological process related to not only animal kingdom but
      also plants. Regarding oxidative stress in plants, heavy metals are frequently
      discussed as causative stimuli with relevance to ecology. Because heavy metals
      have broad technological importance, they can easily contaminate the environment.
      Much of previous effort regarding the harmful impact of the heavy metals was
      given to their toxicology in the animals and humans. Their implication in plant
      pathogeneses is less known and remains underestimated.The current paper
      summarizes basic facts about heavy metals, their distribution in soil, mobility,
      accumulation by plants, and initiation of oxidative stress including the decline
      in basal metabolism. The both actual and frontier studies in the field are
      summarized and discussed. The major pathophysiological pathways are introduced as
      well and link between heavy metals toxicity and their ability to initiate an
      oxidative damage is provided. Mobility and bioaccessibility of the metals is also
      considered as key factors in their impact on oxidative stress development in the
      plant. The metals like lead, mercury, copper, cadmium, iron, zinc, nickel,
      vanadium are depicted in the text.Heavy metals appear to be significant
      contributors to pathological processes in the plants and oxidative stress is
      probably an important contributor to the effect. The most sensitive plant species
      are enlisted and discussed in this review. The facts presented here outline next
      effort to investigate pathological processes in the plants.

PMID- 29032516
TI  - Theoretical investigation on the water-assisted excited-state proton transfer of
      7-azaindole derivatives: substituent effect.
AB  - A systematic study on the first excited-state proton transfer (ESPT) in 2RAI-H2O
      (R = OH, OCH3, CN, NO2, CHO) complexes in solution were investigated at the TD
      M06-2X/6-31 + G(d, p) level. The double proton transfer occurred in an
      asynchronous but concerted protolysis fashion no matter which substituent R was
      used at C2 position in pyrrole ring in the 7AI-H2O complex. The specific
      vibrational-mode of ESPT in the model systems was confirmed and contributed to
      promote the reaction rate by shortening the reaction path. The substituent
      effects of different groups on the ESPT thermodynamics and kinetics were
      discussed. It was obvious that the geometries, barrier height, asynchrony, and
      specific vibration-mode of excited-state proton transfer changed with the
      different substituent groups. Graphical Abstract The distance between two
      neighboring heavy atoms such as N1-O11 (R1) and O11-N8 (R2) distances played an
      important role in the proton transfer reaction. The sum of the N1-O11 and O11-N8
      distances in the reactant of 2RAI-H2O (R=H, OH, OCH3; CN, CHO, NO2) complexes is
      in the range of 5.542 A~5.692 A and changes along with the substituent group at
      C2 position in the pyrrole ring. The ESDPT barrier height and the sum of the N1
      O11 and O11-N8 distances have a good correlation.

PMID- 29032517
TI  - Correction to: A prospective study of corpus callosum regional volumes and
      neurocognitive outcomes following cranial radiation for pediatric brain tumors.
AB  - AbstractThe published version of this article unfortunately contained an error.
      Author "E. Mark Mahone" has been published incorrectly by capturing "Mark Mahone"
      as family name when it should only be "Mahone". Given in this article is the
      corrected name.

PMID- 29032518
TI  - Synchronous solitary calvarial yolk sac tumor metastasis as the initial
      presentation of mediastinal germ cell tumor.
AB  - INTRODUCTION: In children, malignant tumors presenting as a calvarial mass that
      too as initial manifestation are unusual. Also, brain metastases per se are rare
      in pediatric solid tumors with an incidence of just 1.5%. CASE DESCRIPTION: We
      present a child with calvarial metastasis which was the presenting symptom of an
      otherwise asymptomatic large malignant mediastinal germ cell tumor (GCT). The
      lesion was dural-based involving both calvaria as well as the underlying brain
      parenchyma. Despite such multicompartmental location, no obvious bony destruction
      was seen. A 12-year-old boy presented with progressively enlarging scalp swelling
      and features of raised intracranial pressure. The lesion was totally excised and
      calvarial defect reconstructed using titanium mesh. Though the preoperative chest
      computed tomography suggested teratoma, the histopathology of the cranial lesion
      was a yolk sac tumor (YST). CONCLUSION: Initial manifestation of GCT as calvarial
      swelling, pure YST (with no other germ cell component), and the eccentric
      multicompartmental (dural based) location rather than usual midline GCTs is
      noteworthy. The report thus highlights an atypical presentation in GCT. Although
      uncommon, it is worthwhile to consider metastatic GCT as a differential among
      calvarial lesions.

PMID- 29032519
TI  - NMR experiments for the rapid identification of P=O...H-X type hydrogen bonds in
      nucleic acids.
AB  - Hydrogen bonds involving the backbone phosphate groups occur with high frequency
      in functional RNA molecules. They are often found in well-characterized tertiary
      structural motifs presenting powerful probes for the rapid identification of
      these motifs for structure elucidation purposes. We have shown recently that
      stable hydrogen bonds to the phosphate backbone can in principle be detected by
      relatively simple NMR-experiments, providing the identity of both the donor
      hydrogen and the acceptor phosphorous within the same experiment (Duchardt-Ferner
      et al., Angew Chem Int Ed Engl 50:7927-7930, 2011). However, for imino and
      hydroxyl hydrogen bond donor groups rapidly exchanging with the solvent as well
      as amino groups broadened by conformational exchange experimental sensitivity is
      severely hampered by extensive line broadening. Here, we present improved methods
      for the rapid identification of hydrogen bonds to phosphate groups in nucleic
      acids by NMR. The introduction of the SOFAST technique into 1H,31P-correlation
      experiments as well as a BEST-HNP experiment exploiting 3hJN,P rather than 2hJH,P
      coupling constants enables the rapid and sensitive identification of these
      hydrogen bonds in RNA. The experiments are applicable for larger RNAs (up to ~
      100-nt), for donor groups influenced by conformational exchange processes such as
      amino groups and for hydrogen bonds with rather labile hydrogens such as 2'-OH
      groups as well as for moderate sample concentrations. Interestingly, the size of
      the through-hydrogen bond scalar coupling constants depends not only on the type
      of the donor group but also on the structural context. The largest coupling
      constants were measured for hydrogen bonds involving the imino groups of
      protonated cytosine nucleotides as donors.

PMID- 29032520
TI  - Mollib: a molecular and NMR data analysis software.
AB  - Mollib is a software framework for the analysis of molecular structures,
      properties and data with an emphasis on data collected by NMR. It uses an open
      source model and a plugin framework to promote community-driven development of
      new and enhanced features. Mollib includes tools for the automatic retrieval and
      caching of protein databank (PDB) structures, the hydrogenation of biomolecules,
      the analysis of backbone dihedral angles and hydrogen bonds, and the fitting of
      residual dipolar coupling (RDC) and residual anisotropic chemical shift (RACS)
      data. In this article, we release version 1.0 of mollib and demonstrate its
      application to common molecular and NMR data analyses.

PMID- 29032521
TI  - Learning from UJAMBO: Perspectives on Gynecologic Care in African Immigrant and
      Refugee Women in Boston, Massachusetts.
AB  - African-born immigrant women, and particularly refugees and asylum seekers, are
      at risk for reproductive health disparities but inadequately use relevant
      gynecologic services. We sought to elucidate perspectives on gynecologic care in
      a population of Congolese and Somali immigrants. We conducted a secondary
      qualitative analysis of focus group data using a grounded theory approach and the
      Integrated Behavioral Model as our theoretical framework. Thirty one women
      participated in six focus groups. Participant beliefs included the states of
      pregnancy and/or pain as triggers for care, preferences included having female
      providers and those with familiarity with female genital cutting. Barriers
      included stigma, lack of partner support, and lack of resources to access care.
      Experiential attitudes, normative beliefs, and environmental constraints
      significantly mediated care preferences for/barriers to gynecologic health
      service utilization in this population. Centering of patient perspectives to
      adapt delivery of gynecologic care to immigrants and refugees may improve
      utilization and reduce disparities.

PMID- 29032522
TI  - Comparative characteristic of antimicrobial resistance in geriatric hospital: a
      retrospective cohort study.
AB  - BACKGROUND AND AIMS: To examine antimicrobial resistance of commonly isolated
      pathogens in elderly hospitalized patients. METHODS: Data regarding all
      clinically significant isolates from blood and urine cultures of patients
      admitted to a multilevel geriatric hospital during March 2015 to April 2016 were
      collected. Antimicrobial susceptibility testing was performed according to
      Clinical and Laboratory Standard Institute guidelines. RESULTS: Escherichia coli,
      Proteus mirabilis, and Klebsiella pneumoniae were the most common isolates, with
      proportions of extended spectrum beta-lactamase positivity of 60, 40, and 61%
      respectively. Adjusted logistic regression models indicated that resistance of
      Escherichia coli to ceftriaxone [odds ratio (OR) 2.8, 95% confidence interval
      (CI) 1.5-5.1], ceftazidime (OR 2.8, 95% CI 1.5-5.1), ciprofloxacin (OR 2.2, 95%
      CI 1.2-4.0), amoxicillin/clavulanic acid (OR 2.3, 95% CI 1.2-4.3), and
      trimethoprim/sulfamethoxazole (OR 2.4, 95% CI 1.4-4.3) was significantly higher
      in skilled nursing wards than in acute geriatric wards. Resistance of Proteus
      mirabilis to ceftriaxone (OR 3.1, 95% CI 1.5-6.4) and Klebsiella pneumoniae to
      ciprofloxacin (OR 3.2, 95% CI 1.3-7.9) was significantly higher in skilled
      nursing wards than in acute wards. CONCLUSIONS AND DISCUSSION: Antimicrobial
      resistance was found to be high in a multilevel geriatric hospital, especially in
      skilled nursing wards. These findings call for rethinking of the empirical
      antimicrobial therapy and of the efforts for prevention of nosocomial infection.

PMID- 29032523
TI  - Thrombin generation test as a marker for high risk venous thrombosis pregnancies.
AB  - Pregnancy is a well-established risk factor for venous thromboembolism and is
      associated with a state of hypercoagulability. The use of sensitive and specific
      biological markers to predict risk factors for thrombosis is essential during
      pregnancy. Our objective was to investigate the usefulness of thrombin generation
      test (TGT) as a marker to predict the risk of thrombosis in high risk venous
      thrombosis (HRVT) pregnancies compared to normal pregnancies. This retrospective
      study enrolled 134 women with HRVT pregnancies, 78 of whom had monozygotic,
      spontaneous and untreated pregnancies and formed the study group. The control
      group comprised 106 women with normal pregnancies. Routine assessment of
      coagulation activation markers: fibrinogen, D-dimer, prothrombin fragments 1 + 2
      (F1 + 2), thrombin-antithrombin complexes (TAT) and fibrin monomer complexes
      (FMC) was performed every 5 weeks in the study group to detect a possible
      pathological state of hypercoagulability. TGT was performed using platelet-free
      plasma, 1 and 5 pM tissue factor (TF), supplemented by phospholipids (PL) +/-
      thrombomodulin. Fibrinogen, D-dimer, F1 + 2, and TAT, but not FMC, increased
      significantly throughout pregnancy in both groups but no difference was shown
      between the groups. TGT showed an early increase in thrombin generation in both
      groups, which stabilized during the second month of pregnancy. No correlation was
      demonstrated between thrombin generation parameters and coagulation activation
      markers. Based on our results, TGT did not prove conclusive as a marker to
      predict the risk of thrombosis in HRVT pregnancies. Finding a sensitive and
      specific biological marker to predict thrombosis risk requires further
      investigation.

PMID- 29032524
TI  - Patterns and levels of platelet glycosylation in patients with coronary heart
      disease and type 2 diabetes mellitus.
AB  - Coronary heart disease (CHD) and diabetes mellitus (DM) have high reactivity of
      platelets and an increased risk of thrombosis. Platelet glycosylation is closely
      related to platelet function and survival. However, the alteration of platelet
      glycosylation in CHD and T2DM still remains unknown. Platelet samples were
      obtained from 55 healthy controls and 102 patients, including 33 CHD, 30 T2DM and
      39 CHD complicated with T2DM (CHD + T2DM). Platelet glycosylation was detected
      using eight-lectin based assay by flow cytometry. Platelet activation markers,
      such as CD62P (P-Selectin) and activated integrin GPIIb/IIIa (PAC-1), were
      measured on resting and stimulated conditions by flow cytometry. Platelet
      aggregation was measured by light transmission aggregometry. In CHD group,
      platelet surface weakly expressed beta-Gal and 2,6-sialic acid and strongly
      expressed beta-GlcNAc. In T2DM group, lectins binding to platelet of beta-Gal,
      2,6-sialic acid and alpha-mannose were decreased, while alpha1,6-fucose and
      GlcNAc were increased. There was positive correlation between ConA (specific for
      alpha-mannose) and PAC-1 in T2DM patients, while negative correlation in healthy
      controls. Patterns and levels of platelet glycosylation in CHD + T2DM group are a
      combination of CHD group and T2DM group, in addition to the level of ECL highly
      elevated (specific for beta-Gal). The level of ConA was significantly correlated
      with glucose in T2DM group, also correlated with HbA1c in CHD + T2DM. Our
      findings suggested that platelets decreased in sialylation, galactosylation and
      mannosylation, and increased in fucosylation and GlcNAcylation in CHD and T2DM
      patients. The changes of platelet glycosylation may be associated with high
      platelet reactivity and the increased risk of thrombosis in CHD and T2DM.

PMID- 29032525
TI  - Determinants of serum organochlorine pesticide and polychlorinated biphenyl
      levels in middle-aged Korean adults.
AB  - The serum levels of organochlorine pesticides (OCPs) and polychlorinated
      biphenyls (PCBs) were measured in a middle-aged Korean population and
      investigated associations with age, gender, body mass index (BMI), metabolic
      syndrome (MS), type 2 diabetes mellitus (T2DM), and dietary habits. The median
      concentrations of 22 OCPs and 34 PCBs in the serum samples were 483 and 216 ng g
      1 lipid, respectively. The most abundant compound was p,p'-DDE, followed by PCB
      153, beta-HCH, PCB 118, and PCB 180. The results of multiple linear regression
      and other statistical analyses revealed that serum OCP and PCB levels were higher
      in women and were positively correlated with age. BMI was positively associated
      with serum OCP and PCB levels, reflecting the influence of food intake and the
      preserving effect of body fat. MS and T2DM were significantly associated with
      serum OCP and PCB levels. The intake of animal foods had positive associations
      with serum OCP and PCB levels, whereas the intake of phytogenic foods showed
      negative associations, presumably because of contamination levels in food items
      and food matrices that governs absorption and excretion of OCPs and PCBs in the
      body. The relationship between dietary habits and serum OCP and PCB levels were
      different in participants with MS compared to healthy participants, suggesting MS
      may alter the influence of food intake on serum OCP and PCB levels.

PMID- 29032526
TI  - Micro-pollutants in sediment samples in the middle Danube region, Serbia:
      occurrence and risk assessment.
AB  - This is the first comprehensive study on the occurrence of 940 semi-volatile
      organic compounds including sterols, polycyclic aromatic hydrocarbons (PAHs),
      polychlorinated biphenyls (PCBs), pesticides, plasticizers, and other emerging
      compounds in 10 river and canal sediments collected in northern Serbia. For
      quantification of investigated compounds GC-MS-MS (selected reaction monitoring)
      and GC-MS (using both selected ion monitoring and total ion monitoring) methods
      were used. The number of detected compounds was in the range of 85-117, while the
      sum of the concentrations varied from 959 MUg/kg dry-wt to 84,445 MUg/kg dry-wt.
      Sterols were quantified with high frequency in nearly 100% of investigated
      samples suggesting that the studied rivers and canals have been contaminated by
      sewage. Regarding persistent organic compounds, p,p'-DDE, p,p'-DDD, and o,p'-DDT
      were the dominant members of organochlorine pesticides (OCPs). The concentration
      range of 11 quantified pesticides of 452 analyzed was from 0.564 to 61.6 MUg/kg
      dry-wt, while the concentration range of 47 quantified PCBs of 90 analyzed was
      from 0.928 to 32.1 MUg/kg dry-wt. OCPs (DDE, DDD, and gamma-HCH) and several PAHs
      (fluoranthene, pyrene, phenanthrene, chrysene, benzo(a)anthracene,
      benzo(a)pyrene) exceeded the maximum values of the sediment quality guidelines.
      Contents of domestic compounds comprise a large proportion of the total
      contaminant concentration. Overall, the study reveals that river sediments in
      Vojvodina Province were moderately polluted mainly by domestic wastewater. The
      toxic equivalent quantity (TEQ) relative to benzo(a)pyrene and 2,3,7,8
      tetrachlorodibenzodioxin for seven carcinogenic PAHs and six quantified dioxin
      like PCBs ranged from 3.59 to 103 MUg TEQ/kg and from 0.001 * 10-3 to 2.10 * 10-3
      MUg TEQ/kg, respectively, and were in the range or lower than the literature
      published data.

PMID- 29032527
TI  - Spatiotemporal distributions of polycyclic aromatic hydrocarbons close to a
      typical medical waste incinerator.
AB  - Environmental contaminations by polycyclic aromatic hydrocarbons (PAHs)
      especially from incinerators occur subtly, and PAH contribution from this source
      is underestimated. However, as environmental PAH concentrations build up, this
      may be a serious concern around the incinerator vicinity due to the potential
      consequences of PAHs on ecosystems and human health. Thus, the contribution of
      selected (12) PAHs from the Obafemi Awolowo University Teaching Hospital medical
      waste incinerator (or source, HWI_0) was determined by sampling stack gas and
      ambient air around incinerator vicinity from June 2014 to May 2015. Results
      showed that the 12 PAH source (HWI_0) concentrations were in the range of NA (for
      phenanthrene, pyrene, anthracene, benz[e]acephenanthrylene, and indeno[2,1
      b]chromene) to 10.9 ng/m3 (pyrelene) and generally higher than the receptor
      points (hospital waste incinerators (HWIs)). The average total PAH concentrations
      per month at HWI_0 and the receptors-HWI_1, HWI_2, HWI_3, HWI_4 and HWI_5-were
      73.0 +/- 27.9, 60.4 +/- 30.8, 42.5 +/- 23.6, 38.7 +/- 21.9, 35.0 +/- 27.2, and
      39.2 +/- 22.9 ng/m3, respectively. These results and multivariate receptor model
      analysis indicated high correlations between source PAH contributions and the
      receptor points. The PAH concentrations in the dry season were higher than the
      wet season suggesting that hydrological condition affects ambient PAH
      concentrations. The average PAH concentrations in the HWIs as well as the
      cumulative exposure concentrations observed throughout the period are of major
      health concern because PAH concentrations detected are several times higher than
      both the European Union standard and the WHO guideline level.

PMID- 29032528
TI  - Regression and multivariate models for predicting particulate matter
      concentration level.
AB  - The devastating health effects of particulate matter (PM10) exposure by
      susceptible populace has made it necessary to evaluate PM10 pollution.
      Meteorological parameters and seasonal variation increases PM10 concentration
      levels, especially in areas that have multiple anthropogenic activities. Hence,
      stepwise regression (SR), multiple linear regression (MLR) and principal
      component regression (PCR) analyses were used to analyse daily average PM10
      concentration levels. The analyses were carried out using daily average PM10
      concentration, temperature, humidity, wind speed and wind direction data from
      2006 to 2010. The data was from an industrial air quality monitoring station in
      Malaysia. The SR analysis established that meteorological parameters had less
      influence on PM10 concentration levels having coefficient of determination (R 2)
      result from 23 to 29% based on seasoned and unseasoned analysis. While, the
      result of the prediction analysis showed that PCR models had a better R 2 result
      than MLR methods. The results for the analyses based on both seasoned and
      unseasoned data established that MLR models had R 2 result from 0.50 to 0.60.
      While, PCR models had R 2 result from 0.66 to 0.89. In addition, the validation
      analysis using 2016 data also recognised that the PCR model outperformed the MLR
      model, with the PCR model for the seasoned analysis having the best result. These
      analyses will aid in achieving sustainable air quality management strategies.

PMID- 29032530
TI  - Economic and sustainable management of wastes from rice industry: combating the
      potential threats.
AB  - Rice is one of the imperative staple foods, particularly in the developing
      countries. The exponential boom in human population has resulted in the
      continuous expansion in the rice industry in order to meet the food demands. The
      various stages of paddy processing release huge quantity of solid wastes, mainly
      rice husk, rice husk ash and liquid wastes in the form of rice industry
      wastewater. The discharge of the rice industry wastewater imparts a substantial
      threat to the aquatic bodies and the nearby surrounding and, thus, consequently
      demands eco-benign treatment plan. As a result, different strategies are needed
      to enhance the effluent quality and minimize the operational cost of the
      treatment process. Therefore, efficient technological approach targeting the
      minimization of pollution as well as assuring the economic prosperity should be
      implemented. In this review article, several aspects related to the rice industry
      discussing the significant challenges involved in the generation of both solid
      and liquid wastes, mitigation experiments and future prospects have been
      meticulously elaborated. Furthermore, the article also focuses on the various
      processes utilized for reducing the pollution load and promoting the practice of
      reuse and recycle of waste rather than the discharge action for the sake of
      sustainability and the emergence of novel techniques for the generation of energy
      and value-added products.

PMID- 29032529
TI  - Biological and analytical techniques used for detection of polyaromatic
      hydrocarbons.
AB  - Polycyclic aromatic hydrocarbons contain two or more fused benzene rings that are
      considered as cosmo-pollutants ubiquitously found in the environment. The
      identification and monitoring of polycyclic aromatic hydrocarbons (PAHs) are of
      great interests for rapid and on-site detection. Therefore, many analytical and
      biological techniques have been proposed for the qualitative and quantitative
      assessments of PAHs. Non-biological analytical techniques such as infrared,
      Raman, and fluorescence spectroscopies are commonly exploited as non-destructive
      techniques while gas chromatography (GC) and high-performance liquid
      chromatography (HPLC) with multiple detectors are extensively employed for the
      separation and detection of an analyte. Even though spectroscopy and
      chromatography are more accurate, convenient, and feasible techniques, often,
      these methods are expensive and sophisticated which require high maintenance
      cost. On the other hand, biological approaches, i.e., immunoassay, PCR, and
      microarray, offer comprehensive high-throughput specificity and sensitivity for a
      similar analyte. Biosensor- and immunoassay-mediated detections of PAHs have
      opened up new avenues in terms of low cost, rapid determination, and higher
      sensitivity. In this review, we have discussed the strengths and limitations of
      biological and analytical techniques that were explored for precise evaluation
      and were trusted at both the legislation and research levels.

PMID- 29032531
TI  - Bilateral Tolosa-Hunt syndrome mimicking pituitary adenoma.
AB  - The authors report a rare case of bilateral Tolosa-Hunt syndrome, which occurred
      in a 80-year-old female and remitted spontaneously. Inflammatory lesions were
      found not only in typical locations, i.e. superior orbital fissures and cavernous
      sinuses, but also in the pituitary; these imitated gland's macroadenoma in
      imaging studies.

PMID- 29032532
TI  - Genotyping Strains of Lyme Disease Agents Directly From Ticks, Blood, or Tissue.
AB  - The tick-borne spirochetes that cause Lyme disease in North America and Eurasia
      display strong linkage disequilibrium between certain chromosomal and plasmid
      loci within each three major geographic areas of their distribution. For strain
      typing for epidemiologic and ecologic purposes, the commonly used genotypes based
      on a single locus are the spacer between the 16S-23S ribosomal RNA and the ospC
      gene of a plasmid. A simple genotyping scheme based on the two loci allows for
      discrimination between strains representing all the areas of distribution. The
      methods presented here are meant for genotyping directly from ticks and from
      blood and tissue samples from vertebrates.

PMID- 29032533
TI  - Species Identification and Phylogenetic Analysis of Borrelia burgdorferi Sensu
      Lato Using Molecular Biological Methods.
AB  - Bacterial species identification is required in different disciplines and
      depending on the purpose-levels of specificity or resolution of typing may vary.
      Nowadays, molecular methods are the mainstay for bacterial identification and
      sequence-based analyses are of ever-growing importance. For diagnostics,
      immediate results are needed and often real-time PCR of one or two loci is the
      method of choice while for epidemiological or evolutionary studies sequence data
      of several loci improve phylogenetic resolution to required levels. Multilocus
      sequence typing (MLST) and multilocus sequence analyses (MLSA) utilize sequences
      information of several housekeeping loci (eight for Borrelia) to distinguish
      between species. This method has been widely used for bacterial species and
      strain identification and will be described in this chapter.As more and more
      diversity is being detected in the Borrelia burgdorferi sensu lato species
      complex, the importance of accurate species and strain typing has come to the
      fore. This is particularly significant with a view of differentiating human
      pathogenic and non-pathogenic strains or species and understanding the
      epidemiology, ecology, population structure, and evolution of species.

PMID- 29032534
TI  - Generation of Mammalian Host-Adapted Borrelia burgdorferi by Cultivation in
      Peritoneal Dialysis Membrane Chamber Implantation in Rats.
AB  - The transmission, survival, and virulence of Borrelia burgdorferi depend upon the
      spirochete's ability to modulate its transcriptome as it cycles between its
      arthropod vector and reservoir host. This complex adaptive process is
      collectively referred to as "host-adaptation." The paucibacillary nature of
      borrelial infections precludes the detailed analysis of host adaptation within
      infected mammalian tissues. To circumvent this limitation, we (J Clin Invest
      101:2240-2250, 1998) developed a model system whereby spirochetes are cultivated
      within dialysis membrane chambers (DMCs) surgically implanted within the
      peritoneal cavity of a rat. Spirochetes within DMCs are exposed to many, if not
      all, of the environmental signals and physiological cues required for mammalian
      host adaptation but are protected from clearance by the host's immune system.

PMID- 29032535
TI  - Co-immunoprecipitation for Identifying Protein-Protein Interactions in Borrelia
      burgdorferi.
AB  - Co-immunoprecipitation can be utilized to study protein-protein interactions from
      various environments, cell types, or tissues. Herein, we describe a co
      immunoprecipitation protocol that can be used to examine protein complexes found
      in the pathogenic spirochete Borrelia burgdorferi. The method outlined here has
      successfully identified known and unknown members of borrelial protein complexes
      and is an efficient method for studying protein interactions in this pathogenic
      spirochete.

PMID- 29032536
TI  - Characterization of Borrelia burgdorferi Binding to Mammalian Cells and
      Extracellular Matrix.
AB  - Lyme disease Borreliae produces outer surface adhesins to confer bacterial
      attachment to the extracellular matrix (ECM) components on the surface of
      mammalian cells. Here, we describe protocols to characterize the activity and
      specificity of these adhesins by flow cytometry or measurement of the binding of
      radiolabeled spirochetes to immobilized ECM or mammalian cells.

PMID- 29032537
TI  - Analysis of Lipids and Lipid Rafts in Borrelia.
AB  - Lipid rafts are membrane microdomains that are involved in cellular processes
      such as protein trafficking and signaling processes, and which play a fundamental
      role in membrane fluidity and budding. The lipid composition of the membrane and
      the biochemical characteristics of the lipids found within rafts define the
      ability of cells to form microdomains and compartmentalize the membrane. In this
      chapter, we describe the biophysical, biochemical, and molecular approaches used
      to define and characterize lipid rafts in the Lyme disease agent, Borrelia
      burgdorferi.

PMID- 29032538
TI  - Trace Element Analysis of Borrelia burgdorferi by Inductively Coupled Plasma
      Sector Field Mass Spectrometry.
AB  - Transition metal ions play important structural, regulatory, and catalytic roles
      in all biological systems by serving as cofactors for proteins. Due to their
      relatively low levels in the cell compared to abundant metal ions such as
      potassium and magnesium, transition metals are often considered micronutrients
      and referred to as trace elements. Manganese (Mn), iron (Fe), copper (Cu), and
      zinc (Zn) are the most prevalent transition metals in the Lyme disease spirochete
      Borrelia burgdorferi. Here, we describe a method for the accurate measurement of
      these trace elements in B. burgdorferi utilizing inductively coupled plasma
      sector field mass spectrometry (ICP-SFMS).

PMID- 29032539
TI  - Identification and Characterization of Borrelia burgdorferi Complement-Binding
      Proteins.
AB  - Acquisition of host-derived proteins possessing key regulatory function is a
      hallmark of Borrelia burgdorferi, and an important step to successfully infect
      the human host, inhibiting activation of complement as innate immunity's first
      line of defense. Hence, the identification and characterization of interacting
      ligands is a prerequisite to gain deeper insights into the molecular principles
      of how spirochetes overcome the detrimental effects of complement. Far western
      blotting enables the detection of protein-protein interactions in vitro using
      cell lysates containing the prey proteins and purified complement proteins or
      human serum as a source for soluble complement proteins as bait proteins. Here,
      the methodology for the detection and characterization of Borrelia-derived
      proteins interacting with complement regulator Factor H is described, including
      the preparation of whole cell lysates, the separation of proteins by Tris-Tricine
      SDS-PAGE, the transfer of the proteins to nitrocellulose membranes, and the
      detection of Factor H-interacting proteins by Far western.

PMID- 29032540
TI  - Artificial Infection of Ticks with Borrelia burgdorferi Using a Microinjection
      Method and Their Detection In Vivo Using Quantitative PCR Targeting flaB RNA.
AB  - Borrelia burgdorferi is maintained in nature by a tick-rodent infection cycle
      where it traverses and colonizes a variety of host and vector tissues. A tick
      borne murine model has been developed to study Lyme disease in the laboratory,
      which has a substantial impact in advancing our knowledge of spirochete
      infectivity and pathogenesis. Here, we detail a microinjection-based method for
      rapid and efficient infection of ticks with B. burgdorferi. While laboratory
      generation of B. burgdorferi-infected nymphs via natural larval engorgement on
      infected hosts and subsequent molting could take several weeks to months, the
      microinjection-based infection procedure requires only a few hours to generate
      infected ticks and allows introduction of defined quantities of spirochetes,
      including mutant isolates that are attenuated for infection in mice and thus
      cannot be naturally acquired by ticks. We also describe a quantitative PCR-based
      protocol for the measurement of B. burgdorferi in tick and murine hosts targeting
      spirochete RNA that is highly efficient, reproducible, and a better surrogate of
      active infection.

PMID- 29032542
TI  - Borrelia burgdorferi Transcriptome Analysis by RNA-Sequencing.
AB  - Next-Generation Sequencing (NGS) has revolutionized transcriptomics studies in
      the last decade. Transcriptome analysis experiments using NGS-based RNA
      sequencing have several advantages over DNA microarray analysis. Novel
      unannotated transcripts and transcriptional start sites can be identified.
      Differential gene expression can be determined on novel and annotated transcripts
      simultaneously, whereas DNA microarray analysis can only quantify changes of
      known genes. In the protocol below we describe an Illumina compatible ligation
      based method for generating stranded cDNA libraries for total RNA and small RNA
      transcriptomes in Borrelia burgdorferi.

PMID- 29032541
TI  - Borrelia burgdorferi Microarray Analysis.
AB  - Microarray studies have contributed significantly to the current understanding of
      Borrelia burgdorferi genome content and transcriptional regulation. Here, we
      describe the use of microarray technology for several aspects of B. burgdorferi
      genomic analysis.

PMID- 29032543
TI  - Selection of Borrelia burgdorferi Promoter Sequences Active During Mammalian
      Infection Using In Vivo Expression Technology.
AB  - In vivo expression technology (IVET) has been applied to a variety of organisms
      to identify active promoters in specific environments or growth conditions of
      interest. Here, we describe modifications to employ this genome-wide screening
      method for Borrelia burgdorferi, the Lyme disease spirochete, during an active
      murine infection. Utilization of this technique provides valuable insights into
      the B. burgdorferi transcriptome during infection, despite the low bacterial
      numbers in the mammalian host environment.

PMID- 29032544
TI  - Analysis of DNA and RNA Binding Properties of Borrelia burgdorferi Regulatory
      Proteins.
AB  - Bioinformatic approaches and a large volume of prokaryotic genome sequences have
      enabled rapid identification of regulatory proteins with features to bind DNA or
      RNA in a given prokaryote. However, biological relevance of these regulatory
      proteins requires methods to rapidly purify and determine their binding
      properties within the physiological context or life style of the organism. Here,
      we describe the experimental approaches to determine the nucleic acid binding
      properties of regulatory proteins of Borrelia burgdorferi using Borrelia host
      adaptation Re.3gulator (BadR-a DNA binding protein) and Carbon storage regulators
      A of B. b urgdorferi (CsrABb-an RNA binding protein) as examples. Best laboratory
      practices associated with overexpression/purification of recombinant borrelial
      proteins, synthesis of target nucleic acid sequences, and electrophoretic
      mobility assays to assess the protein/nucleic acid interactions are described.
      The methods described are intended to facilitate empirical assessment of the
      binding affinity, co-factor requirements, quality of the interacting partners,
      and readily modifiable assay conditions to assess the binding properties to
      define known and unknown regulatory properties of nucleic acid binding proteins
      of B. burgdorferi.

PMID- 29032545
TI  - Identification of Acetylated Proteins in Borrelia burgdorferi.
AB  - Posttranslational modification (PTM) of proteins has emerged as a major
      regulatory mechanism in all three domains of life. One emerging PTM is Nepsilon
      lysine acetylation-the acetylation of the epsilon amino group of lysine residues.
      Nepsilon-lysine acetylation is known to regulate multiple cellular processes. In
      eukaryotes, it regulates chromatin structure, transcription, metabolism, signal
      transduction, and the cytoskeleton. Recently, multiple groups have detected
      Nepsilon-lysine acetylation in diverse bacterial phyla, but no work on protein
      acetylation in Borrelia burgdorferi has been reported. Here, we describe a step
      by-step protocol to identify Nepsilon-lysine acetylated proteins in B.
      burgdorferi.

PMID- 29032546
TI  - Genetic Transformation and Complementation.
AB  - The disciplines of Borrelia (Borreliella) burgdorferi microbiology and Lyme
      disease pathogenesis have come to depend on the genetic manipulation of the
      spirochete. Generating mutants in these recalcitrant bacteria, while not
      straightforward, is routinely accomplished in numerous laboratories, although
      there are several crucial caveats to consider. This chapter describes the design
      of basic molecular genetic experiments as well as the detailed methodologies to
      prepare and transform competent cells, select for and isolate transformants, and
      complement or genetically restore mutants.

PMID- 29032548
TI  - Generation of Conditional Mutants in Borrelia burgdorferi.
AB  - Mutational studies aimed at characterizing the function(s) of bacterial genes
      required for growth or viability are constrained by the inability to generate
      deletion strains lacking the gene of interest. To circumvent this limitation, it
      is possible to generate conditional mutants in which a copy of the gene of
      interest is introduced into the bacteria to compensate for the loss of the native
      allele. Expression of the non-native copy of the target gene is typically under
      control of an inducible promoter, which allows for controllable and regulated
      production of the gene of interest. Conditional mutants are also broadly useful
      for phenotypic analyses of genes that require a tightly regulated and
      artificially inducible copy of the target gene. Herein, we describe the methods
      used to generate and confirm conditional mutant clones in Borrelia burgdorferi
      utilizing the Borrelia-adapted lac operator/repressor system.

PMID- 29032547
TI  - Genome-Wide Mutagenesis in Borrelia burgdorferi.
AB  - Signature-tagged mutagenesis (STM) is a functional genomics approach to identify
      bacterial virulence determinants and virulence factors by simultaneously
      screening multiple mutants in a single host animal, and has been utilized
      extensively for the study of bacterial pathogenesis, host-pathogen interactions,
      and spirochete and tick  biology. The signature-tagged transposon mutagenesis has
      been developed to investigate virulence determinants and pathogenesis of Borrelia
      burgdorferi. Mutants in genes important in virulence are identified by negative
      selection in which the mutants fail to colonize or disseminate in the animal host
      and tick vector. STM procedure combined with Luminex Flex(r)MapTM technology and
      next-generation sequencing (e.g., Tn-seq) are the powerful high-throughput tools
      for the determination of Borrelia burgdorferi virulence determinants. The
      assessment of multiple tissue sites and two DNA resources at two different time
      points using Luminex Flex(r)MapTM technology provides a robust data set. B.
      burgdorferi transposon mutant screening indicates that a high proportion of genes
      are the novel virulence determinants that are required for mouse and tick
      infection. In this protocol, an effective signature-tagged Himar1-based
      transposon suicide vector was developed and used to generate a sequence-defined
      library of nearly 4800 mutants in the infectious B. burgdorferi B31 clone. In
      STM, signature-tagged suicide vectors are constructed by inserting unique DNA
      sequences (tags) into the transposable elements. The signature-tagged transposon
      mutants are generated when transposon suicide vectors are transformed into an
      infectious B. burgdorferi clone, and the transposable element is transposed into
      the 5'-TA-3' sequence in the B. burgdorferi genome with the signature tag. The
      transposon library is created and consists of many sub-libraries, each sub
      library has several hundreds of mutants with same tags. A group of mice or ticks
      are infected with a mixed population of mutants with different tags, after
      recovered from different tissues of infected mice and ticks, mutants from output
      pool and input pool are detected using high-throughput, semi-quantitative
      Luminex(r) FLEXMAPTM or next-generation sequencing (Tn-seq) technologies. Thus
      far, we have created a high-density, sequence-defined transposon library of over
      6600 STM mutants for the efficient genome-wide investigation of genes and gene
      products required for wild-type pathogenesis, host-pathogen interactions, in
      vitro growth, in vivo survival, physiology, morphology, chemotaxis, motility,
      structure, metabolism, gene regulation, plasmid maintenance   and replication,
      etc. The insertion sites of 4480 transposon mutants have been determined. About
      800 predicted protein-encoding genes in the genome were disrupted in the STM
      transposon library. The infectivity and some functions of 800 mutants in 500
      genes have been determined. Analysis of these transposon mutants has yielded
      valuable information regarding the genes and gene products important in the
      pathogenesis and biology of B. burgdorferi and its tick vectors.

PMID- 29032549
TI  - Detection of Bioluminescent Borrelia burgdorferi from In Vitro Cultivation and
      During Murine Infection.
AB  - Borrelia burgdorferi, etiologic agent of Lyme disease, is the leading tick-borne
      disease in the United States with approximately 300,000 cases diagnosed annually.
      Disease occurs in stages beginning localized infection at the site of a tick bite
      and progresses to disseminated infection when antibiotic treatment is not
      administered in a timely manner. A multi-systemic infection develops following
      dissemination to numerous immunoprotective tissues, such as the heart, bladder,
      and joints, resulting in late Lyme disease. B. burgdorferi undergoes dynamic
      genetic regulation throughout mammalian infection and defining the exact role of
      virulence genes at distinct stages of disease is challenging. The murine model
      allows for the characterization of the pathogenic function of genes in B.
      burgdorferi, but traditional end point studies limit the ability to gather data
      throughout an infection study and greatly increase the required number of mice.
      Molecular genetic techniques to evaluate and quantitate B. burgdorferi infection
      are laborious and costly. To partly circumvent these issues, a codon optimized
      firefly luciferase, under the control of a constitutive borrelial promoter, was
      introduced into B. burgdorferi enabling the characterization of mutant or
      modified strains under in vitro growth conditions and throughout murine
      infection. The detection of bioluminescent B. burgdorferi is highly sensitive and
      allows for the repeated real-time quantitative evaluation of borrelial load
      during murine infection. Furthermore, bioluminescence has also been utilized to
      evaluate alteration in tissue localization and tissue-specific gene expression of
      B. burgdorferi. In this chapter, we describe the generation of bioluminescent
      borrelial strains along with methods for in vitro, in vivo, and ex vivo B.
      burgdorferi studies.

PMID- 29032550
TI  - Analysis of Borrelia burgdorferi Proteome and Protein-Protein Interactions.
AB  - The proteome of Borrelia burgdorferi undergoes dynamic alterations as the microbe
      cycles through and persists in diverse host or vector environments. Therefore,
      studies of B. burgdorferi proteome and protein-protein interactions, which play
      central roles in biological processes in diverse organisms, are critical in
      understanding biology and infectivity of spirochetes. Here, we describe the
      proteomic analysis of B. burgdorferi by two-dimensional (2-D) gel electrophoresis
      followed by protein identification via liquid chromatography-mass spectrometry
      and database searching. We also describe assays for studying the interaction
      between borrelial proteins: a novel high-throughput luciferase assay, yeast two
      hybrid assay, and a far-Western assay that are routinely used in our
      laboratories.

PMID- 29032551
TI  - Two Photon Intravital Microscopy of Lyme Borrelia in Mice.
AB  - Two-photon intravital microscopy is a powerful tool that allows visualization of
      cells in intact tissues in a live animal in real time. In recent years, this
      advanced technology has been applied to understand pathogen-host interactions
      using fluorescently labeled bacteria. In particular, infectious fluorescent
      transformants of the Lyme disease spirochete Borrelia burgdorferi, an Ixodes tick
      transmitted pathogen, have been imaged by two-photon intravital microscopy to
      study bacterial motility and interactions of the pathogen with feeding ticks and
      host tissues. Here, we describe the techniques and equipment used to image
      mammalian-adapted spirochetes in the skin of living mice in vivo and in joints ex
      vivo using two-photon intravital microscopy.

PMID- 29032552
TI  - Investigating Human Dendritic Cell Immune Responses to Borrelia burgdorferi.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells that recognize
      and phagocytose pathogens, and help to orchestrate adaptive immune responses to
      combat them. DCs are abundant in the skin where Borrelia burgdorferi first enters
      the body during a tick bite, and are thus critical in determining the initial
      stages of the innate and adaptive immune responses against Borrelia. Here, we
      describe two methods to study the response of DCs to Borrelia; an in vitro
      approach using monocyte-derived DCs (moDCs) and an ex vivo approach using a human
      skin model.

PMID- 29032553
TI  - Phagocytosis Assays for Borrelia burgdorferi.
AB  - Phagocytosis of Borrelia burgdorferi, the causative agent of Lyme disease, is a
      poorly understood process, despite its importance during the host immune response
      to infection. Thus, macrophages infiltrate the infected tissues, including the
      base of the heart and phagocytose the spirochete, therefore contributing to their
      elimination from infected tissues and leading to inflammation. An impaired
      bacterial clearance will result in bacterial persistence that may interfere with
      normal physiology of the heart, such as electrical signals from the heart,
      resulting in an impaired coordination of the beating of the heart or "heart
      block." This chapter presents a protocol for establishing primary mouse
      macrophage cultures, a method for lentivirus silencing of primary cells, and a
      method for the in vitro study of macrophage phagocytosis of fluorescently labeled
      Borrelia burgdorferi.

PMID- 29032554
TI  - Measuring Borrelia burgdorferi Motility and Chemotaxis.
AB  - Swimming plate, cell motion tracking, and capillary tube assays are very useful
      tools to quantitatively measure bacterial motility and chemotaxis. These methods
      were modified and applied to study Borrelia burgdorferi motility and chemotaxis.
      By using these methods, numerous motility and chemotaxis mutants have been
      characterized and several chemoattractants were identified. With the assistance
      of these tools, the role of motility and chemotaxis in the pathogenicity of B.
      burgdorferi has been established. In addition, these tools also facilitate the
      study of motility and chemotaxis in other spirochetes.

PMID- 29032555
TI  - In Vitro Models of Cutaneous Inflammation.
AB  - The skin plays an essential role in the transmission of Lyme borreliosis since it
      is the first interface between the Ixodes tick and the host during the
      inoculation of Borrelia burgdorferi sensu lato. A better understanding of the
      inflammatory reaction at this location is key to develop better strategies (e.g.,
      vaccine and diagnosis) to fight this disease. In vitro cell culture of resident
      skin cells might constitute an approach to decipher the complex interplay between
      the tick, the pathogen, and the vertebrate host.

PMID- 29032556
TI  - Magnetic Isolation of Phagosomes Containing Toll-Like Receptor Ligands.
AB  - Phagosomal compartments are critical in microbial defense as vesicles that
      degrade invading organisms. In a broader context, vesicular trafficking plays an
      important role in shuttling many different types of cargo that are critical for
      proper function of the cell. Endosomal and phagosomal vesicles are thus important
      locations for the assembly of intracellular signaling platforms that mediate host
      responses to invasive pathogens such as Borrelia burgdorferi. Isolation of
      phagosomes from cells is an important technique that allows for a detailed study
      of phagosomal components and signaling complex assembly. However, purification of
      phagosomes had previously been challenging and it has been difficult to obtain
      sufficient purity of the phagosomal fractions. Here, we modify a new magnetic
      isolation technique that greatly simplifies purification of phagosomes and
      isolates vesicles with sufficient purity for analysis.

PMID- 29032557
TI  - Xenodiagnosis Using Ixodes scapularis Larval Ticks in Humans.
AB  - Xenodiagnosis is the use of a natural vector to detect the presence of an
      organism, and xenodiagnosis using Ixodes ticks has long been used by
      entomologists in Lyme disease research to provide evidence of the host's
      infectious status with Borrelia burgdorferi. We developed the methodology and
      performed the first human research study using uninfected larval Ixodes
      scapularis ticks to assess evidence of B. burgdorferi infection. Here, we
      describe in detail the methodology used for the procedure. Xenodiagnosis using
      Ixodes ticks in humans remains an experimental method and must be performed under
      an approved clinical research protocol.

PMID- 29032559
TI  - Evolving Concepts in Pulmonary Hypertension.

PMID- 29032558
TI  - Recombinant E. coli Dualistic Role as an Antigen-adjuvant Delivery Vehicle for
      Oral Immunization.
AB  - Escherichia coli is the mainstay tool for fundamental microbiology research due
      to its ease of cultivation and safety. Auxotrophic strains of the K-12 and B
      lineages of E. coli are the organisms of choice to produce recombinant proteins.
      Components present in the cell envelope of bacteria are also potent immune
      modulators and have been used to develop adjuvants. We used live E. coli, after
      induction of recombinant protein expression, to develop a vehicle which has a
      dualistic function of producing vaccine while presenting itself as the adjuvant
      to deliver oral vaccines against a number of infectious diseases, including Lyme
      disease. Here, we give an example using E. coli expressing B. burgdorferi Outer
      Surface Protein A, which was proven effective in reducing B. burgdorferi burden
      in infected ticks after a 5-year field trial of a baited formulation containing
      this reservoir targeted vaccine.

PMID- 29032560
TI  - Pulmonary Hypertension: Definition, Classification, and Diagnosis.

PMID- 29032561
TI  - Pathology and Pathobiology of Pulmonary Hypertension.

PMID- 29032562
TI  - Genetics of Pulmonary Arterial Hypertension.

PMID- 29032563
TI  - Screening of Pulmonary Arterial Hypertension.

PMID- 29032564
TI  - Idiopathic Pulmonary Arterial Hypertension: Evolving Therapeutic Strategies.

PMID- 29032565
TI  - Pulmonary Hypertension Complicating Connective Tissue Disease.

PMID- 29032566
TI  - Pulmonary Arterial Hypertension Complicating Congenital Heart Disease: Advances
      in Therapy.

PMID- 29032567
TI  - Pulmonary Hypertension Due to Left Heart Disease.

PMID- 29032568
TI  - Chronic Thromboembolic Pulmonary Hypertension: Advances in Therapy.

PMID- 29032569
TI  - Medical Treatment of Pulmonary Arterial Hypertension.

PMID- 29032570
TI  - Lung Transplantation for Pulmonary Hypertension and Strategies to Bridge to
      Transplant.

PMID- 29032571
TI  - Quantity of Lymph Nodes in the Vascularized Lymph Node Transfer Influences Its
      Lymphaticovenous Drainage.
AB  - BACKGROUND:  The purpose of this study was to: (1) evaluate the mechanism of
      lymph drainage through a vascularized lymph node (VLN) flap, and (2) investigate
      if the number of VLNs impacts lymph transit time through the flap. METHODS: 
      Twenty-seven axillary VLN flaps were elevated in 14 Sprague-Dawley rats and
      divided into three groups (n = 9 each) based on the number of lymph nodes
      present: group 1 (0-VLNs), group 2 (2-VLNs), and group 3 (4-VLNs). Indocyanine
      green (n = 8/group) and Alexa680-albumin (n = 1/group) were injected into the
      edge of flaps and the latency period between injection and fluorescence in the
      axillary vein was recorded. Stereomicroscopic fluorescent lymphography was
      performed to directly visualize lymphatic transit through VLNs. RESULTS: 
      Fluorescence was detected in the axillary vein after 229s [47-476], 79s [15-289],
      and 56s [16-110] in group 1, 2, and 3, respectively (p < 0.01). There was a
      negative correlation between the number of VLNs in the flap and the latency
      period (r = -0.59; p < 0.05). Median flap weights were comparable in group 1, 2,
      and 3 (258 mg [196-349], 294 mg [212-407], 315 mg [204-386], respectively; p =
      0.54). Stereoscopic lymphography allowed direct visualization of lymphatic fluid
      transit through VLNs. CONCLUSION:  Lymphatic fluid in VLN flaps drains into the
      venous system mainly by passing through the afferent lymphatics and lymph nodes.
      A secondary mechanism appears to be the diffusion of fluid into the venous system
      via intratissue lymphaticovenous connections created during flap elevation.
      Increasing the number of lymph nodes in the flap is associated with a more rapid
      transit of fluid.

PMID- 29032572
TI  - Effect of enterovirus infections on asthma in young children: A national cohort
      study.
AB  - BACKGROUND: We conducted a cohort study to determine the relationship between
      enterovirus (EV) infection and asthma. MATERIALS AND METHODS: From the National
      Health Insurance Research Database of Taiwan, we identified patients who received
      a new diagnosis of asthma and concurrent treatment between January 2000 and
      December 2011 (EV cohort: n = 208 213; non-EV cohort: n = 208 213). Cox
      proportional hazards regression analysis was performed to determine and compare
      the adjusted hazard ratios (aHRs) of asthma between these 2 cohorts. Kaplan-Meier
      analysis was conducted to assess the differences in the cumulative incidence
      curves of asthma between the 2 cohorts. RESULTS: The overall aHR of asthma was
      1.48-fold higher in the EV cohort than in the non-EV cohort (95% confidence
      interval = 1.45-1.50). The aHR of asthma was higher in the EV cohort than in the
      non-EV cohort, comprising children aged <=5 years, regardless of sex,
      sociodemographic factors (urbanization level and parental occupation) or
      comorbidities. The risk of asthma was higher in 1-3, 4-6, 7-9 and 10-12 months
      (all P < .001), particularly in those with a higher frequency of admission (>5
      per year). CONCLUSION: The incidence of asthma was higher in the EV cohort than
      in the non-EV cohort, comprising children aged <=5 years, regardless of sex,
      urbanization level, parental occupation or season. In particular, the risk of
      asthma was higher in children with a higher frequency of admission, even in the
      absence of atopy or other respiratory infections.

PMID- 29032573
TI  - Protein biomarker of cell proliferation determines survival to discharge in cases
      of equine large colon volvulus.
AB  - BACKGROUND: Progenitor cells play critical roles in epithelial repair following
      ischaemic injury. Protein biomarkers have been used to identify intestinal
      progenitor cell subpopulations. This study aims to determine if a critical number
      of intestinal progenitor cells can predict tissue viability and survival to
      discharge of large colon volvulus (LCV) cases. OBJECTIVES: The objectives were to
      1) identify intestinal progenitor cell subpopulations using biomarkers:
      proliferating cell nuclear antigen (PCNA), sex determining region Y box 9 (SOX9),
      phospho-histone H3 (PHH3) and Ki-67, 2) define cut-off values for critical
      numbers of positive cells and 3) determine if survival to discharge is associated
      with cut-off values. STUDY DESIGN: Retrospective cohort study. METHODS: Adult
      horses admitted to the Farm and Equine Veterinary Medical Center at NC State's
      Veterinary Hospital and Peterson and Smith Equine Hospital between 2006 and 2016
      that underwent an exploratory coeliotomy with a diagnosis of LCV of >=360
      degrees, had pelvic flexure biopsy and that recovered from general anaesthesia
      were selected for inclusion in the study. Immunohistochemical analyses were
      performed and positive cells were counted. Optimal cut-off values were determined
      using receiver operator curves. A Fisher's exact test was used to associate cut
      off values with survival to discharge. RESULTS: In this study, 23 cases of LCV
      >=360 degrees  were included. Of 23 horses, 13 (57%) survived to discharge. A cut
      off value of <2.1 PHH3 positive cells per crypt correctly predicted death with
      100% sensitivity (95% CI; 69.15-100%) and 84.62% specificity (95% CI; 54.55
      98.08%). LCV cases with <2.1 PHH3 positive cells per crypt were 96.6 times more
      likely to die (95% CI; 4.14-2255 and P < 0.0001). Biomarkers PCNA, SOX9 and Ki-67
      did not predict short-term survival. MAIN LIMITATIONS: The population size was
      small. CONCLUSIONS: PHH3 immunohistochemical analysis may assist in more accurate
      prediction of survival to hospital discharge of LCV cases. The summary is
      available in Spanish - see Supporting Information.

PMID- 29032574
TI  - Five-year outcomes of a randomized clinical trial comparing bone-level implants
      with either submerged or transmucosal healing.
AB  - AIM: To evaluate the long-term hard and soft tissue peri-implant tissue stability
      of bone-level implants using a different implant placement protocol (submerged
      versus transmucosal). MATERIALS AND METHODS: This study was partly a subset
      analysis of a multicentre study where in 40 patients, a single bone-level implant
      with platform switching and a conical implant-abutment interface was placed
      either submerged or transmucosal in non-molar sites. Changes in the peri-implant
      tissues between implant placement and 5 years were assessed clinically and
      radiologically. Patient-related outcomes were also recorded. RESULTS: Thirty
      patients completed the 5-year follow-up. Implant survival rate was 100%. The mean
      radiographic changes in crestal bone levels between baseline and 5 years were
      0.59 (0.92) mm and 0.78 (1.03) mm for the submerged and the transmucosal groups,
      respectively. No statistical significant differences were found between the
      groups for any of the investigated variables. Peri-implantitis, defined as
      changes in the level of crestal bone of >=2 mm together with bleeding on probing,
      was only diagnosed in one patient. Patients in both groups were highly satisfied
      with the treatment received. CONCLUSIONS: Bone-level implants with submerged or
      transmucosal healing protocols demonstrated similar outcomes after 5 years. Both
      protocols yielded optimal clinical and radiographic results when bone-level
      implants were placed in non-molar positions for single tooth replacement.

PMID- 29032575
TI  - Decreased Expression of IFNG-AS1, IFNG and IL-1B Inflammatory Genes in Medicated
      Schizophrenia and Bipolar Patients.
AB  - Although aberrant expression of cytokines such as IL-1B and IFNG in blood from
      psychiatric patients supports a role of inflammation in the pathogenesis of the
      disease, little is known about mechanisms underlying their regulation. We aimed
      to evaluate the putative role of IFNG-AS1 long non-coding RNA (lncRNA) in
      controlling of IFNG locus in patients with schizophrenia (SZ) and bipolar (BP).
      We analysed the expression levels of IFNG-AS1 long non-coding RNA, and IFNG and
      IL-1B mRNAs in blood cells from 27 SZ- and 30 BP-medicated patients and in 32
      healthy controls. Our data showed that IFNG-AS1 expression dramatically decreased
      in BP and SZ patients compared with controls and was significantly correlated
      with IFNG expression in patients specifically. Transcript levels of IL-1B were
      also significantly reduced in BP and SZ patients compared with controls. No
      significant differences in the expression of IFNG-AS1, IFNG and IL-1B genes were
      found between patients with BP and SZ. Our data shed further light on the
      potential role of inflammation, and more particularly inflammatory lncRNAs, in SZ
      and BP diseases and their pharmacological treatment.

PMID- 29032576
TI  - Hispanane-Type Diterpenoid and Secoiridoid Glucosides from Viburnum cylindricum.
AB  - Three hitherto unknown compounds, including one new hispanane-type diterpenoid
      glucoside, namely viburnumoside (1), two new secoiridoid glucosides, 7alpha
      galloyloxysweroside (2), and 7beta-galloyloxysweroside (3), together with ten
      known compounds (4 - 13) were isolated from the ethanol extract of twigs and
      leaves of Viburnum cylindricum. Their structures were elucidated on the basis of
      extensive spectroscopic studies, and the absolute configuration of compound 1 was
      confirmed by the experimental and calculated electronic circular dichroism (ECD)
      data.

PMID- 29032578
TI  - First trimester screening for pre-eclampsia in Chinese pregnancies: case-control
      study.
AB  - OBJECTIVE: To assess the potential of screening for pre-eclampsia (PE) in a
      Chinese population. DESIGN: Case-control study. SETTING: Teaching hospital in
      Hong Kong. POPULATION: A total of 3330 women having a viable singleton pregnancy
      attending first-trimester Down-syndrome screening. METHODS: Mean arterial
      pressure (MAP), bilateral uterine artery pulsatility index (UtA-PI), and
      placental growth factor (PlGF) were measured. Screening markers were transformed
      to multiples of the gestational median (MoM) and adjusted for maternal and
      pregnancy characteristics. MoM distributions in PE and non-PE pregnancies were
      compared with published expected values. PE screening performance was assessed
      using area under receiver operating curves (AUROC). MAIN OUTCOME MEASURES: PE
      detection rate. RESULTS: A total of 30 (0.9%) women developed either early (<34
      weeks) or late (>=34 weeks) onset PE. MAP was dependent on maternal BMI, UtA-PI
      on fetal crown rump length, uterine artery peak systolic velocity (UtA-PSV) on
      maternal age and gestation, and PlGF on gestation in non-PE pregnancies. MoM
      distributions determined using published Fetal Medicine Foundation models
      deviated significantly from one for both MAP (P < 0.0001) and PI (P < 0.0001),
      but not PlGF (P = 0.52) in non-PE pregnancies, whilst PlGF MoM distributions in
      those who developed early as opposed to late onset PE were significantly higher
      (P = <0.05). AUROC for any PE using multiple markers was 0.72 (95% CI: 0.64-0.81)
      with detection rates of 72 and 55% for early and late PE, respectively, for a 10%
      false positive rate. CONCLUSION: Detection rates for PE in our Chinese population
      were lower than the expected 90-95% even after adjusting MoM for local women's
      characteristics. FUNDING: General Research Fund (Project number 470513).
      TWEETABLE ABSTRACT: Pre-eclampsia screening in the Chinese population had
      detection rates lower than previously published results.

PMID- 29032577
TI  - Pyruvate kinase isozyme M2 and glutaminase might be promising molecular targets
      for the treatment of gastric cancer.
AB  - The aim of this study was to analyze the significance of glucose metabolism
      related enzymes in the proliferation of gastric cancer under hypoxia. Four
      hypoxia-resistant gastric cancer cell lines and four parent cell lines were used.
      Reverse transcription-PCR was used to evaluate the mRNA expression levels of the
      following metabolism-related enzymes: pyruvate kinase isozyme M2 (PKM2),
      glutaminase (GLS), enolase 1 (ENO1), glucose-6-phosphate dehydrogenase (G6PDH),
      and PKM1. The effects of these enzymes on the proliferation of gastric cancer
      cells were examined using siRNAs, shikonin as a PKM2 inhibitor, or BPTES as a GLS
      inhibitor, in vitro and in vivo. Levels of both PKM2 and GLS mRNA were
      significantly high in all hypoxia-resistant cell lines, compared with those of
      their parent cells. Knockdown of PKM2 and GLS significantly decreased the
      proliferation of all hypoxia-resistant cells. The combination of siPKM2 and siGLS
      significantly decreased proliferation compared with treatment by siPKM2 or siGLS
      alone. The knockdown of ENO1, G6PDH, or PKM1 did not decrease the proliferation
      of all hypoxia-resistant cells. Combination treatment using shikonin and BPTES
      inhibited the proliferation of all hypoxia-resistant cancer cells more than that
      by either agent alone. The in vivo study indicated that the tumor size treated by
      the combination of shikonin and BPTES was significantly smaller than that of
      vehicle-treated group. These findings suggested that PKM2 and GLS might play
      important roles in the proliferation of hypoxic gastric cancer cells. A
      combination of PKM2 and GLS inhibitors could be therapeutically promising for the
      treatment of gastric cancer.

PMID- 29032579
TI  - Incidentally detected testicular lesions <10 mm in diameter: can orchidectomy be
      avoided?
AB  - OBJECTIVE: To investigate the pathology of excised testicular lesions <10 mm in
      size. PATIENTS AND METHODS: The pathological reports of 2 681 patients with
      testicular lesions from Barts Health NHS Trust and Oxford University Hospitals
      NHS Foundation Trust were reviewed as part of a service evaluation audit from
      January 2003 to May 2016. Cases in which the lesion had a maximum diameter of <10
      mm were selected. Clinical features were also accessed, where available, to
      examine patient demographics, prediagnostic levels of serum markers,
      ultrasonographic findings and clinical details. RESULTS: A total of 81 patients
      with a lesion size <10 mm on histology were identified and, of these, 16 (20%)
      had a lesion diameter <5 mm. Of the 81 patients, 56 (69%) had benign lesions. Of
      16 patients with a benign lesion <5 mm in diameter, 15 underwent orchidectomy and
      just one underwent partial orchidectomy. Preoperative tumour markers were
      available in 47/81 patients. None of the 16 malignant tumours in these 47
      patients were associated with raised tumour markers, while seven of 31 remaining
      patients with benign lesions had raised alpha-fetoprotein and lactate
      dehydrogenase levels. In total there were 25/81 malignant cases (31%), which were
      all germ cell tumours (GCTs): 15 seminomas (60%) and 10 non-seminomatous GCTs
      (40%). Only one GCT had a diameter of <5 mm, and this was a regressed tumour
      within an 18-mm area of granulomatous inflammation. Only one GCT relapsed: a
      clinical stage I, embryonal carcinoma of 6 mm in maximum diameter. The 56
      'benign' cases included 34 sex cord stromal tumours, including 23 Leydig cell
      tumours (41%), eight Sertoli cell tumours (14%) and three mixed sex cord stromal
      tumours (5%). None showed any malignant features. The remaining 22/56 lesions
      (40%) were lesions with no further follow-up. Benign lesions seemed to be
      associated with a small diameter, and we found <5 mm to be the best threshold for
      predicting benign vs malignant lesions (P = 0.002). CONCLUSION: The majority of
      testicular lesions <10 mm, identified by radiology, were benign, although
      approxmiately one-third were malignant. In the present study, 100% of lesions <5
      mm in diameter were benign. Tumour markers appear to be unhelpful in the
      distinction of these small tumours. We suggest that regular ultrasound
      surveillance be more widely used for testicular lesions of this size. Testicular
      tumours now have a very high cure rate and changes in size of lesions may be
      monitored prospectively with minimal risk of increased morbidity. Patients who
      undergo an orchidectomy for lesions <5 mm are 'victims of modern imaging
      technology'. If surgery is undertaken in lesions 5-10 mm, patients should be
      counselled that two-thirds of cases are benign.

PMID- 29032580
TI  - Impact of ureteroscopy before radical nephroureterectomy for upper tract
      urothelial carcinomas on oncological outcomes: a meta-analysis.
AB  - OBJECTIVES: To investigate whether ureteroscopy (URS) before radical
      nephroureterectomy (RNU) for upper tract urothelial carcinomas (UTUCs) has an
      impact on oncological outcomes. PATIENTS AND METHODS: We performed a systematic
      literature search of PubMed, Web of Science, and EMBASE for citations published
      prior to September 2017 that described URS performed on patients with UTUC and
      conducted a standard meta-analysis on survival outcomes. RESULTS: Our meta
      analysis included eight eligible studies containing 3975 patients. The results
      were as follows: cancer-specific survival (CSS; hazard ratio [HR] 0.76, 95%
      confidence interval [CI] 0.59-0.99; P = 0.04), overall survival (OS; HR 0.76, 95%
      CI 0.48-1.21; P = 0.24), recurrence-free survival (RFS; HR 0.89, 95% CI 0.69
      1.14; P = 0.37), metastasis-free survival (MFS; HR 1.06, 95% CI 0.82-1.36; P =
      0.66), and intravesical recurrence-free survival (IRFS; HR 1.51, 95% CI 1.29
      1.77; P < 0.001). When excluding previous bladder tumour history, the result for
      IRFS was a HR of 1.81 (95% CI 1.53-2.13; P < 0.001). CONCLUSIONS: This meta
      analysis indicated that URS before RNU did not have a negative impact on CSS, OS,
      RFS, or MFS in patients with UTUC. However, patients were at higher risk of
      intravesical recurrence after RNU when they had undergone URS before RNU. Further
      studies are needed to assess the effects of post-URS intravesical chemotherapy on
      intravesical recurrence.

PMID- 29032581
TI  - Utilization and quality outcomes of cT1a, cT1b and cT2a partial nephrectomy:
      analysis of the national cancer database.
AB  - OBJECTIVE: To describe the utilization and compare quality outcomes of partial
      nephrectomy (PN) for cT1a, cT1b and cT2a renal masses using a large national
      database. METHODS: We conducted a retrospective analysis of patients from the US
      National Cancer Database who underwent PN for cT1a/cT1b/T2a renal cell carcinoma
      between 2004 and 2013. We examined the use of PN over time and assessed quality
      indicators [positive surgical margin (PSM) and 30-day postoperative readmission
      rates]. Multivariable analysis was conducted to determine predictors for outcome
      comparisons. RESULTS: A total of 43 749 patients underwent PN for cT1a, cT1b and
      cT2a renal masses (cT1a, n = 34 796; cT1b, n = 8 040; cT2a, n = 913). The
      proportion of patients undergoing PN increased from 30.8% in 2004 to 56.7% in
      2013 (P < 0.001), and this trend was apparent for all clinical stages. The PSM
      rate was 6.8%. Predictive factors for increased risk of PSMs included cT1a stage
      (P = 0.03), age [odds ratio (OR) 1.01; P < 0.001] and later year of diagnosis
      (OR: 1.05; P < 0.001). The 30-day readmission rate was 4.2%. Predictive factors
      for increased risk of readmission included cT1b (P < 0.001), high Charlson
      comorbidity score (OR: 1.32; P = 0.001) and lack of private insurance (OR: 1.21
      1.97; P < 0.05); later year of diagnosis was associated with decreased odds of
      readmission (OR: 0.96; P < 0.001). Subset analysis of the 2010-2013 cohort showed
      increases in the proportion of minimally invasive PN for cT1a (52.8-69.6%; P <
      0.001), cT1b (39.9-59.6%; P < 0.001) and cT2a tumours (33.3-47.3%; P = 0.01). The
      PSM rate was also increased, at 7.3%. Predictive factors for PSMs included
      increasing age (OR: 1.01; P < 0.001), minimally invasive surgical approach (OR:
      1.52; P < 0.001), and conversion to open surgery (OR: 1.52; P = 0.01), but not
      clinical stage (P = 0.75-0.99). The 30-day readmission rate was 4.0%. Predictive
      factors for readmission included lack of private insurance (P < 0.001) and
      conversion to open surgery (OR: 1.63; P < 0.001). CONCLUSION: The use of PN has
      increased significantly over time for all clinical stage groups. PSM rates
      increased, while 30-day readmission rates decreased. The PSM rate increase was
      driven by increasing use of minimally invasive approaches, and not by higher
      clinical stage. The 30-day readmission rate was driven by patient comorbidities
      and socio-economic factors. Rising PSM rates represent a quality-of-care concern.

PMID- 29032582
TI  - National cohort study comparing severe medium-term urinary complications after
      robot-assisted vs laparoscopic vs retropubic open radical prostatectomy.
AB  - OBJECTIVES: To evaluate the occurrence of severe urinary complications within 2
      years of surgery in men undergoing either robot-assisted radical prostatectomy
      (RARP), laparoscopic radical prostatectomy (LRP) or retropubic open radical
      prostatectomy (ORP). PATIENTS AND METHODS: We conducted a population-based cohort
      study in men who underwent RARP (n = 4 947), LRP (n = 5 479) or ORP (n = 6 873)
      between 2008 and 2012 in the English National Health Service (NHS) using national
      cancer registry records linked to Hospital Episodes Statistics, an administrative
      database of admissions to NHS hospitals. We identified the occurrence of any
      severe urinary or severe stricture-related complication within 2 years of surgery
      using a validated tool. Multi-level regression modelling was used to determine
      the association between the type of surgery and occurrence of complications, with
      adjustment for patient and surgical factors. RESULTS: Men undergoing RARP were
      least likely to experience any urinary complication (10.5%) or a stricture
      related complication (3.3%) compared with those who had LRP (15.8% any or 5.7%
      stricture-related) or ORP (19.1% any or 6.9% stricture-related). The impact of
      the type of surgery on the occurrence of any urinary or stricture-related
      complications remained statistically significant after adjustment for patient and
      surgical factors (P < 0.01). CONCLUSION: Men who underwent RARP had the lowest
      risk of developing severe urinary complications within 2 years of surgery.

PMID- 29032583
TI  - Third Generation Ventricular Assist Device: Mid-Term Outcomes of the HeartWare
      HVAD in Pediatric Patients.
AB  - The HeartWare HVAD is a small, third generation continuous flow pump that is
      intracorporeally placed for support of a failing ventricle in adult patients.
      This device is small in size when compared to other left ventricular assist
      devices and can therefore be used in smaller sized pediatric patients. We present
      our initial experience using the HVAD as a bridge to heart transplantation in the
      pediatric population. We performed a retrospective, single center, nonrandomized
      review of 17 pediatric patients who underwent HVAD implantation between June 2013
      and March 2016. The primary endpoints evaluated in this study were overall
      survival to heart transplantation, ongoing device support, or death. In this
      patient cohort, nine (53%) of 17 patients were male. The median age of the
      patients was 13.4 +/- 3.8 (range 5-17) years. The median body surface area was
      1.4 +/- 0.4(0.7-2) m2 . Etiologies of heart failure requiring HVAD support were
      dilated cardiomyopathy (n = 8), myocarditis (n = 5) and noncompaction
      cardiomyopathy (n = 4). The overall mean length of HVAD support was 254 +/- 298
      (range 2-804) days. A successful outcome (bridge to transplant and ongoing
      mechanical support) was achieved in 13 patients (76.5%). Of the 13 patients, nine
      (69.2%) were bridged to heart transplantation and four continue to receive
      support (30.7%) and are eligible for transplantation. Post-transplant survival
      has been 100%, with a mean follow-up of 296 +/- 264.5 (range 18-785) days. The
      most common complication was pump thrombosis (23.5%) in follow-up. Four patients
      (23.5%) experienced no complications. The HVAD continuous flow ventricular assist
      device can be safely used to bridge pediatric patients to cardiac
      transplantation. Favorable outcomes of this device are comparable to the adult
      population. This analysis demonstrated safe and effective implantation of the
      HVAD System in a child with a BSA of 0.7 m2 .

PMID- 29032584
TI  - Assessment of microbial diversity in the rhizosphere of Pinus roxburghii (Sarg.)
      and bio-inoculant potential of selected pine bacterial isolates for wheat
      varieties based on cultureindependent and culture-dependent techniques.
AB  - Evidence is lacking regarding compatibility of pine bacteria as bio-inoculants
      for crops. The diversity and abundance of rhizosphere bacteria of Pinus
      roxburghii has never been investigated with simultaneous application of culture
      dependent and culture-independent techniques. The present study was aimed to
      isolate, characterise, check the bio-inoculant potential of pine bacteria and
      assess rhizosphere bacterial diversity using culture-independent advanced
      approaches. Forty bacteria isolated from the rhizoplane of P. roxburghii growing
      in a cold climate at high altitude in Murree, were morphologically characterised;
      nine were identified by 16S rRNA sequence analyses and used in experiments.
      Diversity and abundance of the 16S rRNA gene and nifH gene in the rhizosphere was
      assessed by cloning, RFLP analysis, 454-amplicon pyrosequencing and qPCR. The
      bacterial isolates significantly improved dry weight of shoot, root, root area,
      IAA and GA3 content, number of grains plant-1 , weight of grains plant-1 in wheat
      varieties Chakwal-50 and Fareed-06 under axenic and field conditions. The number
      of 16S rRNA sequences (2979) identified by pyrosequencing shared similarity with
      13 phyla of bacteria and archaea. The results confirm the existence of diverse
      bacteria of agricultural and industrial importance in the rhizosphere and
      compatibility of rhizoplane bacteria as bio-inoculants for wheat varieties.

PMID- 29032585
TI  - Infection surveillance in pediatric hematopoietic stem cell transplantation
      recipients.
AB  - OBJECTIVE: To describe the profile of reported healthcare-associated infections
      (HAIs) in pediatric patients submitted to hematopoietic stem cell transplantation
      (HSCT) at a reference center. METHODS: Retrospective cohort of pediatric patients
      who were submitted to HSCT from 2008 to 2016. The criteria for HAI were based on
      those established by the National Healthcare Safety Network. Data were collected
      by active surveillance performed daily by professionals. This study was approved
      by the institutional research ethics committee. RESULTS: A total of 86 HSCTs were
      performed in 81 patients younger than 18 years of age (median, 10 years). Of
      these, 69 (85%) were males. Aplastic anemia and leukemia were the main diagnoses.
      A total of 140 HAIs were diagnosed with an incidence density of 28.2
      infections/1000 patient-days. The most common HAI was laboratory-confirmed
      bloodstream infection (46), the majority of which was reported to be central
      venous catheter-associated (43). Gram-negative bacteria were the most prevalent
      microorganisms (58.5%). Almost all the infections occurred until 30 days after
      transplantation, and 17 deaths were observed within 180 days after the procedure.
      CONCLUSION: Active surveillance of HAIs in HSCT children allowed the evaluation
      of the incidence and profile of HAIs, which is essential for the health care of
      these patients.

PMID- 29032586
TI  - Cohesion and centromere activity are required for phosphorylation of histone H3
      in maize.
AB  - Haspin-mediated phosphorylation of histone H3 at threonine 3 (H3T3ph) promotes
      proper deposition of Aurora B at the inner centromere to ensure faithful
      chromosome segregation in metazoans. However, the function of H3T3ph remains
      relatively unexplored in plants. Here, we show that in maize (Zea mays L.)
      mitotic cells, H3T3ph is concentrated at pericentromeric and centromeric regions.
      Additional weak H3T3ph signals occur between cohered sister chromatids at
      prometaphase. Immunostaining on dicentric chromosomes reveals that an inactive
      centromere cannot maintain H3T3ph at metaphase, indicating that a functional
      centromere is required for H3T3 phosphorylation. H3T3ph locates at a newly formed
      centromeric region that lacks detectable CentC sequences and strongly reduced CRM
      and ZmBs repeat sequences at metaphase II. These results suggest that centromeric
      localization of H3T3ph is not dependent on centromeric sequences. In maize
      meiocytes, H3T3 phosphorylation occurs at the late diakinesis and extends to the
      entire chromosome at metaphase I, but is exclusively limited to the centromere at
      metaphase II. The H3T3ph signals are absent in the afd1 (absence of first
      division) and sgo1 (shugoshin) mutants during meiosis II when the sister
      chromatids exhibit random distribution. Further, we show that H3T3ph is mainly
      located at the pericentromere during meiotic prophase II but is restricted to the
      inner centromere at metaphase II. We propose that this relocation of H3T3ph
      depends on tension at the centromere and is required to promote bi-orientation of
      sister chromatids.

PMID- 29032587
TI  - Team preparation for human uterus transplantation: Autologous transplantation in
      sheep model.
AB  - We performed autologous uterus transplantation using the living-sheep donor model
      for team preparation before human uterine transplantation. Five sequential
      operations (in 3 ewes) were prospectively conducted. Surgical technique included
      uterus retrieval, graft preparation, and uterus transplantation. Anastomoses were
      performed at the level of the external iliac. At 3-week follow-up, the uterus and
      anastomoses were checked for strictures and thrombosis. Two successful auto
      transplantations were made, and one failed because of undeveloped uterine
      arteries (< 1 mm in diameter). In the first two ewes, we identified and used a
      deep, separate uterine vein, which was not described in other publications. In
      the third ewe, we used the utero-ovarian vein. The team was able to perform safe
      dissection and auto-transplantation, with no signs of strictures or thrombosis
      after 3 weeks. Cold ischemic time was 60 minutes, and warm ischemic time was
      between 40 and 60 minutes, with no need for re-anastomoses. We noticed that using
      the deep uterine vein in the sheep model can anatomically simulate better the
      human uterine vein and the difficulty to approach it. To avoid using unsuitable
      vessels for anastomoses, the uterine transplantation protocol in humans should
      include imaging of the donor's uterine vessels.

PMID- 29032588
TI  - Clinical significance of lactate clearance for the development of early allograft
      dysfunction and short-term prognosis in deceased donor liver transplantation.
AB  - This retrospective study evaluated lactate clearance (LC), measured at 6, 12, 18,
      and 24 hours after reperfusion, as a predictor of early allograft dysfunction
      (EAD) and short-term outcomes in patients receiving deceased donor liver
      transplantation. Of 181 transplant recipients, 44 (24.3%) developed EAD and had
      lower LCs than those who did not develop EAD. A receiver operating characteristic
      analysis showed that LC determined at 6 hours showed the highest area under curve
      value of 0.828 (95% confidence interval [CI]: 0.755-0.990) for predicting the
      development of EAD at a cutoff value of 25.8% with 76.7% sensitivity and 77.9%
      specificity. LC values that fell below the cutoff values were significantly
      associated with EAD in a multivariate analysis, with values at 6 hours having the
      highest adjusted odds ratio (11.891, 95% CI: 4.469-31.639). In-hospital and 6
      month mortalities were higher in patients with LC values below the cutoffs
      compared with those above the cutoff values at each time point. Thus, LC
      calculated shortly after reperfusion of an allograft is significantly
      discriminative for the development of EAD and is associated with short-term
      prognosis after deceased donor liver transplantation.

PMID- 29032589
TI  - Microscopic assessment of the tissue-sparing potential of radiofrequency-assisted
      liver resection techniques in a porcine model.
AB  - BACKGROUND: The aim of the present study was to microscopically assess the tissue
      sparing potential of contemporary radiofrequency-assisted liver resection (RF-LR)
      techniques. METHODS: Twenty-four pigs were subjected to either (1) partial
      hepatectomy (PH) using the sequential-coagulate-cut (SCC) technique (group SCC, n
      = 6) using a monopolar electrode, the technique using the bipolar electrode Habib
      4X (group H, n = 6) or the "crush-clamp" technique (group CC, n = 6); or (2) sham
      operation (group Sham, n = 6). At 48 h post-operation, liver parenchyma proximal
      to the ablation rim was excised for histopathologic examination and
      immunohistochemical assessment of apoptosis (antibody M30) and inflammatory
      response (antibodies IL-6, TNFalpha and NFkappaB). RESULTS: Histopathologic index
      increased from the 1st to the 4th , the 1st to the 2nd or only the 1st cm from
      the inner margin of the ablation rim in group SCC, H or CC, respectively. The
      index was higher in group SCC compared to the other groups. Tissue expression of
      M30, IL-6, TNFalpha and NFkappaB increased in all PH groups, being higher and
      more expanded in group SCC, H, SCC and SCC, respectively. CONCLUSIONS: RF-LR
      techniques had variable microscopically assessed tissue-sparing effect. The Habib
      4X proved to be less injurious compared to the SCC Belgrade technique regarding
      the severity and extent of tissue damage proximal to the ablation rim.

PMID- 29032590
TI  - A scoping approach to systematically review published reviews: Adaptations and
      recommendations.
AB  - Knowledge translation is a central focus of the health research community, which
      includes strategies to synthesize published research to support uptake within
      health care practice and policy arenas. Within the literature concerning review
      methodologies, a new discussion has emerged concerning methods that review and
      synthesize published review articles. In this paper, our multidisciplinary team
      from family medicine, nursing, dental hygiene, kinesiology, occupational therapy,
      physiology, population health, clinical psychology, and library sciences
      contributes to this discussion by sharing our experiences in conducting 3 scoping
      reviews of published review studies. A brief discussion of Cochrane Collaboration
      overview reviews and Joanna Briggs Institute umbrella reviews foreshadows a
      discussion of insights from our experiences of conducting the 3 scoping reviews
      of published reviews. We address 6 adaptations along with our recommendations for
      each, which may guide other researchers with designing scoping review approaches
      to synthesize published reviews. The ability of researchers to publish research
      findings is growing, and our ability to effectively transfer findings into useful
      evidence for health care practice and policy is imperative to our work.

PMID- 29032592
TI  - Arabidopsis EARLY FLOWERING3 increases salt tolerance by suppressing salt stress
      response pathways.
AB  - Arabidopsis EARLY FLOWERING3 (ELF3) functions in modulating light input to the
      circadian clock, as a component of ELF3-ELF4-LUX ARRHYTHMO (LUX) evening complex.
      However, the role of ELF3 in stress responses remains largely unknown. In this
      study, we show that ELF3 enhances plants' resilience to salt stress: ELF3
      overexpressing (ELF3-OX) plants are salt-tolerant, while elf3 mutants are more
      sensitive to salt stress. The expressions of many salt stress- and senescence
      associated genes are altered in elf3-1 and ELF3-OX plants compared with wild
      type. During salt stress, ELF3 suppresses factors that promote salt stress
      response pathways, mainly GIGANTEA (GI), at the post-translational level, and
      PHYTOCHROME INTERACTING FACTOR4 (PIF4), at the transcriptional level. To enhance
      the salt stress response, PIF4 directly downregulates the transcription of
      JUNGBRUNNEN1 (JUB1/ANAC042), encoding a transcription factor that upregulates the
      expression of stress tolerance genes, DREB2A and DELLA. Furthermore, PIF4
      directly upregulates the transcription of ORESARA1 (ORE1/ANAC092) and SAG29,
      positive regulators of salt stress response pathways. Based on our results, we
      propose that ELF3 modulates key regulatory components in salt stress response
      pathways at the transcriptional and post-translational levels.

PMID- 29032593
TI  - Association analysis of the ACTN3 R577X polymorphism with passive muscle
      stiffness and muscle strain injury.
AB  - Passive muscle stiffness is considered to be a major factor affecting joint
      flexibility and is thought to relate to the occurrence of muscle strain injury.
      In skinned muscle fiber experiments, the R577X polymorphism of the alpha-actinin
      3 gene (ACTN3) has been associated with passive muscle stiffness. Our primary
      purpose was to clarify whether the ACTN3 R577X polymorphism influences passive
      stiffness of human muscle in vivo. We also examined whether the ACTN3 R577X
      polymorphism is associated with the occurrence of hamstring strain injury.
      Seventy-six healthy young male subjects were genotyped for the ACTN3 R577X
      (rs1815739) polymorphism. Shear modulus (an index of stiffness) of each hamstring
      muscle (biceps femoris, semitendinosus, and semimembranosus) was assessed using
      ultrasound shear wave elastography, and history of hamstring strain injury was
      collected via a questionnaire. The muscle shear moduli of the semitendinosus and
      semimembranosus were significantly higher in R-allele (RR + RX genotype) carriers
      than in XX genotype carriers, whereas the shear modulus of the biceps femoris did
      not differ among the ACTN3 R577X genotypes. Frequency of past hamstring strain
      injury also did not differ between the 3 genotypes nor between the R-allele and
      XX genotype carriers. This study indicates that RR and RX genotypes of the ACTN3
      R577X polymorphism (corresponding to the presence of alpha-actinin-3 in type II
      muscle fibers) are associated with increased passive muscle stiffness of the
      human hamstring in vivo. However, this altered mechanical property might not
      affect the risk of hamstring muscle strain injury.

PMID- 29032594
TI  - Implementation of AICAR analysis by GC-C-IRMS for anti-doping purposes.
AB  - AICAR (5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside), is a naturally
      occurring substance which is part to the World Anti-Doping Agency (WADA)
      Prohibited List. It is claimed to improve physical performance when administered
      as a supplement. As for other endogenous compounds such as steroids, the gas
      chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) analysis
      remains an efficient tool to differentiate endogenous substances from exogenous
      ones. A protocol was described in the literature for the analysis of AICAR by GC
      C-IRMS. The aim of the present study was to implement this protocol in our
      laboratory and to propose solutions to avoid the difficulties encountered. The
      first point discussed in this study is the derivatization step. Due to the
      structure of the AICAR molecule, conventional derivatization for GC-C-IRMS such
      as acetylation could not be applied and silylation was preferred. The improvement
      of the derivatives stability was achieved thanks to several derivatization
      conditions tested. This adjustment led to a reproducible derivatization pattern
      with the 3-TMS form as major derivative product. The second point discussed in
      this study is the diminution of extracts' background noise. Indeed, the
      implementation of the published protocol was not easy due to high performance
      liquid chromatography (HPLC) problems encountered when concentrated urine was
      injected into our system. Also, too many interferences in the endogenous
      reference compound fractions were observed. The addition of both a wash step
      before the HPLC purification and a HPLC purification step for the endogenous
      reference compound (ERC) fraction allowed us to increase the robustness of the
      method. This study presents the modified protocol compared to the original
      protocol as well as the evaluation of the whole method performances. Copyright
      (c) 2017 John Wiley & Sons, Ltd.

PMID- 29032595
TI  - Born at the right time? A conceptual framework linking reproduction, development,
      and settlement in reef fish.
AB  - Parents are expected to make decisions about reproductive timing and investment
      that maximize their own fitness, even if this does not maximize the fitness of
      each individual offspring. When offspring survival is uncertain, selection
      typically favors iteroparity, which means that offspring born at some times can
      be disadvantaged, while others get lucky. The eventual fate of offspring may be
      further modified by their own decisions. Are fates of offspring set by birthdates
      (i.e., determined by parents), or can offspring improve upon the cards they've
      been dealt? If so, do we see adaptive plasticity in the developmental timing of
      offspring? We evaluate these questions for a coral reef fish (the sixbar wrasse,
      Thalassoma hardwicke) that is characterized by extreme iteroparity and flexible
      larval development. Specifically, we monitored larval settlement to 192 small
      reefs over 11 lunar months and found that most fish settled during new moons of a
      lunar cycle (consistent with preferential settlement on dark nights). Settlement
      was significantly lower than expected by chance during the full moon and last
      quarter of the lunar cycle (consistent with avoidance of bright nights). Survival
      after settlement was greatest for fish that settled during times of decreasing
      lunar illumination (from last quarter to new moon). Fish that settled on the last
      quarter of the lunar cycle were ~10% larger than fish that settled during other
      periods, suggesting larvae delay settlement to avoid the full moon. These results
      are consistent with a numerical model that predicts plasticity in larval
      development time that enables avoidance of settlement during bright periods.
      Collectively, our results suggest that fish with inauspicious birthdates may
      alter their developmental trajectories to settle at better times. We speculate
      that such interactions between parent and offspring strategies may reinforce the
      evolution of extreme iteroparity and drive population dynamics, by increasing the
      survival of offspring born at the "wrong" time by allowing them to avoid the
      riskiest times of settlement.

PMID- 29032596
TI  - Limited effect of adaptive immune response to control encephalitozoonosis.
AB  - This study revises our understanding of the effectiveness of cell-mediated
      adaptive immunity and treatment against microsporidia using molecular detection
      and quantification of microsporidia in immunocompetent C57Bl/6 and
      immunodeficient CD4-/- and CD8-/- mice for the first time. We demonstrate an
      intense dissemination of microsporidia into most organs within the first weeks
      post-infection in all strains of mice, followed by a chronic infection
      characterized by microsporidia persistence in CD4-/- and C57Bl/6 mice and a
      lethal outcome for CD8-/- mice. Albendazole application reduces microsporidia
      burden in C57Bl/6 and CD4-/- mice, whereas CD8-/- mice experience only a
      temporary effect of the treatment. Surprisingly, treated CD8-/- mice survived the
      entire experimental duration despite enormous microsporidia burden. On the basis
      of our results, we conclude that microsporidia survive despite the presence of
      immune mechanisms and treatments that are currently considered to be effective
      and therefore that CD8 T lymphocytes represent a major, but not sole effector
      mechanism controlling microsporidiosis. Furthermore, the survival of mice does
      not correspond to spore burden, which provides new insight into latent
      microsporidiosis from an epidemiological point of view.

PMID- 29032597
TI  - Congenital cytomegalovirus in Japan: More than 2 year follow up of infected
      newborns.
AB  - BACKGROUND: The aim of this study was to evaluate the outcome of congenital
      cytomegalovirus (CMV) infection identified on urine-filter screening assay at >2
      years' follow up, and to observe the clinical outcomes after anti-CMV treatment.
      METHODS: Sixty of 72 congenital CMV patients were enrolled and clinically
      observed for >2 years. Forty-three were asymptomatic at birth; seven were
      symptomatic at birth but untreated with anti-CMV drugs; and 10 were symptomatic
      and treated with anti-CMV drugs. RESULTS: Of the 43 asymptomatic patients, three
      developed hearing loss or language disability for which association with
      congenital CMV has been repeatedly reported, and two had neurological sequelae of
      which the etiology was unclear, indicating that the rate of CMV-associated late
      onset sequelae was 7-12%. All seven symptomatic infants without treatment
      developed sequelae, while three of the 10 treated patients were free from any
      sequelae. CONCLUSIONS: The rate of late-onset sequelae observed in Japan is
      similar to that reported in the USA and Europe. The treatment of symptomatic
      patients with antiviral agents results in favorable clinical outcomes. Thus,
      newborn urine-filter paper screening of congenital CMV infection is warranted.

PMID- 29032598
TI  - Ynamide Preactivation Allows a Regio- and Stereoselective Synthesis of alpha,beta
      Disubstituted Enamides.
AB  - A novel ynamide preactivation strategy enables the use of otherwise incompatible
      reagents and allows preparation of alpha,beta-disubstituted enamides with high
      regio- and stereoselectivity. Mechanistic analysis reveals the intermediacy of a
      triflate-bound intermediate as a solution-stable, effective keteniminium
      reservoir, whilst still allowing subsequent addition of organometallic reagents.

PMID- 29032599
TI  - IMPACT-III is a valid and reliable questionnaire for assessing health-related
      quality of life in Swedish children with inflammatory bowel disease.
AB  - AIM: This study examined the reliability, validity and factor structure of the
      Swedish version of the IMPACT-III questionnaire for assessing health-related
      quality of life in children with inflammatory bowel disease. METHODS: We
      recruited 202 participants aged eight to 18 years, who were enrolled from 16 of
      the 23 paediatric gastroenterology clinics across Sweden during 2010-2013. This
      cross-sectional study compared two versions of the IMPACT-III questionnaire - one
      with six factors and 35 items and one with four factors and 19 items - plus the
      Paediatric Quality of Life Inventory 4.0 Generic Core Scale. Disease activity was
      assessed and defined as active or inactive. RESULTS: The mean total score for the
      six-factor IMPACT-III scale was 143.7/175, with a standard deviation (SD) of
      17.9. There was a significant difference in mean total scores between the 133
      children with inactive disease (147.8, SD: 14.9) and the 52 with active disease
      (133.0, SD: 20.3). Confirmatory factor analysis showed that the four-factor scale
      was more robust than the original six-factor scale. Concurrent validity and
      discriminant validity were high for both versions. CONCLUSION: The Swedish
      version of the IMPACT-III questionnaire was valid and reliable, but the shorter,
      four-factor version is quicker and may be more convenient in clinical settings.

PMID- 29032600
TI  - Synthesis and Characterization of the Hemi-Salen Ligands and Their Triboron
      Complexes: Spectroscopy and Examination of Anticancer Properties.
AB  - The synthesis, spectroscopic properties, and in vitro cytotoxicity activity of a
      series of various salen-based triboron complexes have been designed and prepared
      from hemi-salen (L1 H3  - L4 H3 ) ligands and BF3 .Et2 O or BPh3 under simple
      reaction conditions. The hemi-salen (L1 H3  - L4 H3 ) ligands and their BF2 or
      BPh2 chelating triboron complexes were characterized by means of NMR (1 H, 13 C,
      19 F, and 11 B) spectra, FT-IR spectra, UV/VIS spectra, fluorescence spectra,
      mass spectra, melting point, as well as elemental analysis. The triboron [L(1 -
      4) (BF2 )3 ] and [L(1 - 4) (BPh2 )3 ] complexes were investigated for their
      absorption and emission properties, and these complexes are also good chelates
      towards boron(III) fragments such as BF2 or BPh2 quantum yield in solution
      reaching up to 38%. The hemi-salen (L1 H3  - L4 H3 ) ligands and their BF2 or
      BPh2 chelating triboron complexes were tested for the in vitro anticancer
      activity against various cancer and normal cells (HeLa, DLD-1, ECC-1, PC-3, PNT
      1A, and CRL-4010), and it was found that the cell viability of cancer cells was
      decreased while most of the healthy cells could still be viable. Also, the
      cytotoxicity studies showed that anticancer activity of hemi-salen (L1 H3  - L4
      H3 ) ligands is higher than that of triboron [L(1 - 4) (BF2 )3 ] and [L(1 - 4)
      (BPh2 )3 ] complexes. The hemi-salen (L1 H3  - L4 H3 ) ligands showing the
      strongest cytotoxic effect in PC-3 cells were found to exhibit anticancer
      activity with apoptosis by increasing the level of ROS in the PC-3 cells.

PMID- 29032602
TI  - Muscle-specific differences in expression and phosphorylation of the Janus kinase
      2/Signal Transducer and Activator of Transcription 3 following long-term
      mechanical ventilation and immobilization in rats.
AB  - AIM: Muscle wasting is one of the factors most strongly predicting mortality and
      morbidity in critically ill intensive care unit (ICU). This muscle wasting
      affects both limb and respiratory muscles, but the understanding of underlying
      mechanisms and muscle-specific differences remains incomplete. This study aimed
      at investigating the temporal expression and phosphorylation of the Janus
      kinase/signal transducer and activator of transcription (JAK/STAT) pathway in
      muscle wasting associated with the ICU condition to characterize the JAK/STAT
      proteins and the related changes leading or responding to their activation during
      exposure to the ICU condition. METHODS: A novel experimental ICU model allowing
      long-term exposure to the ICU condition, immobilization and mechanical
      ventilation, was used in this study. Rats were pharmacologically paralysed by
      post-synaptic neuromuscular blockade and mechanically ventilated for durations
      varying between 6 hours and 14 days to study muscle-specific differences in the
      temporal activation of the JAK/STAT pathway in plantaris, intercostal and
      diaphragm muscles. RESULTS: The JAK2/STAT3 pathway was significantly activated
      irrespective of muscle, but muscle-specific differences were observed in the
      temporal activation pattern between plantaris, intercostal and diaphragm muscles.
      CONCLUSION: The JAK2/STAT3 pathway was differentially activated in plantaris,
      intercostal and diaphragm muscles in response to the ICU condition. Thus,
      JAK2/STAT3 inhibitors may provide an attractive pharmacological intervention
      strategy in immobilized ICU patients, but further experimental studies are
      required in the study of muscle-specific effects on muscle mass and function in
      response to both short- and long-term exposure to the ICU condition prior to the
      translation into clinical research and practice.

PMID- 29032601
TI  - Persistent regional and racial disparities in nondirected living kidney donation.
AB  - Nondirected living donors (NDLDs) are an important and growing source of kidneys
      to help reduce the organ shortage. In its infancy, NDLD transplantation was
      clustered at a few transplant centers and rarely benefited African American (AA)
      recipients. However, NDLDs have increased 9.4-fold since 2000, and now are often
      used to initiate kidney paired donation chains. Therefore, we hypothesized that
      the initial geographic clustering and racial disparities may have improved. We
      used Scientific Registry of Transplant Recipients data to compare NDLDs and their
      recipients between 2008-2015 and 2000-2007. We found that NDLD increased an
      average of 12% per year, from 20 in 2000 to 188 in 2015 (IRR: 1.12, 95% CI: 1.11
      1.13, P < .001). In 2000-2007, 18.3% of recipients of NDLD kidneys were AA; this
      decreased in 2008-2015 to 15.7%. NDLD transplants initially became more evenly
      distributed across centers (Gini 0.91 in 2000 to Gini 0.69 in 2011), but then
      became more clustered at fewer transplant centers (Gini 0.75 in 2015). Despite
      the increased number of NDLDs, racial disparities have worsened and the center
      level distribution of NDLD transplants has narrowed in recent years.

PMID- 29032603
TI  - Isolated innominate artery dissection.

PMID- 29032604
TI  - The impact of intercenter sharing on the outcomes of pediatric split liver
      transplantation.
AB  - BACKGROUND: Split liver transplantation allows for expansion of the pool of
      organs available for pediatric liver transplantation. The impact of sharing
      segments of the same liver between centers has not been studied. STUDY DESIGN:
      Retrospective analysis of 24 pediatric split liver transplant cases in a recent
      cohort. We evaluated the outcomes of pediatric recipients who shared organs with
      adult patients in our own center (group A) compared to recipients who shared
      organs with adult patients in other centers. (group B). RESULTS: One-, 3-, and 5
      year graft survival for group A was 100%, 100%, and 100% vs 83%, 71%, and 57% for
      group B (P = .039). Postoperative complications included biliary complications
      (41.7% in group A vs 50% in group B, P = .682), vascular complications (8.3% in
      group A vs 41.7% in group B, P = .059), and postoperative bleeding (16.7% in
      group A vs 25% in group B, P = .615). High-grade Clavien-Dindo complications were
      0% in group A vs 33.3% in group B, P = .028. CONCLUSIONS: Organ sharing between
      centers appears to be associated with significantly poorer graft survival.
      Possible explanations include greater procurement-related injury or suboptimal
      vessel distribution. Future larger studies focused on this area may be helpful to
      formulate policy considerations.

PMID- 29032605
TI  - Nonapoptotic functions of Fas/CD95 in the immune response.
AB  - CD95 (also known as Fas) is a member of the tumor necrosis factor receptor (TNFR)
      superfamily. Its cognate ligand, CD95L, is implicated in immune homeostasis and
      immune surveillance. Mutations in this receptor are associated with a loss of
      apoptotic signaling and have been detected in an autoimmune disorder called
      autoimmune lymphoproliferative syndrome (ALPS) type Ia, which shares some
      clinical features with systemic lupus erythematosus (SLE). In addition, deletions
      and mutations of CD95 have been described in many cancers, which led researchers
      to initially classify this receptor as a tumor suppressor. More recent data
      demonstrate that CD95 engagement evokes nonapoptotic signals that promote
      inflammation and carcinogenesis. Transmembrane CD95L (m-CD95L) can be cleaved by
      metalloproteases, releasing a soluble ligand (s-CD95L). Soluble and membrane
      bound CD95L show different stoichiometry (homotrimer versus multimer of
      homotrimers, respectively), which differentially affects CD95-mediated signaling
      through molecular mechanisms that remain to be elucidated. This review discusses
      the biological roles of CD95 in light of recent experiments addressing how a
      death receptor can trigger both apoptotic and nonapoptotic signaling pathways.

PMID- 29032606
TI  - How Chi Sequence Modifies RecBCD Single-Stranded DNA Translocase Activity.
AB  - E. coli RecBCD initiates homologous repair as well as degrades foreign DNA.
      Recognition of chi sequence (5'-GCTGGTGG-3') switches RecBCD from a destructive,
      nucleolytic mode into a repair-active one that promotes RecA-mediated
      recombination. RecBCD includes a 3'-to-5' single-stranded DNA (ssDNA) translocase
      in RecB subunit, a 5'-to-3' translocase in RecD, and a secondary translocase
      activity associated with RecBC. To understand how chi specifically affects each
      translocase activity, we directly visualized individual RecBCD translocating
      along DNA substrates containing a ssDNA gap of different polarities, with or
      without chi. Disappearance of RecBCD from the ssDNA signals the loss of the ssDNA
      translocase activity. For substrates containing a ssDNA gap that RecBCD
      encounters in the 3'-to-5' polarity (3'-to-5' ssDNA), wild-type RecBCD disappears
      from the DNA substrates with similarly high percentage, either with chi or
      without. This suggests that (1) the 3'-to-5' translocase in RecB is unaffected by
      chi and (2) it is low in processivity. With substrates containing a ssDNA gap
      that RecBCD encounters in the 5'-to-3' polarity (5'-to-3' ssDNA), we found that
      the leaving percentage increases significantly with chi, implying inactivation of
      the 5'-to-3' translocase of RecD upon chi recognition. Surprisingly, the RecD
      defective mutant RecBCDK177Q showed only ~50 % leaving on 5'-to-3' ssDNA,
      directly revealing the presence of RecBC secondary translocase and its activity
      is unaffected by chi. Multiple ssDNA translocases within the RecBCD complex both
      before and after chi ensures processive unwinding of DNA substrates required for
      efficient recombination events.

PMID- 29032607
TI  - Erythroblast macrophage protein (Emp): Past, present, and future.
AB  - This review is a journey of the landmark erythroblast macrophage protein (Emp)
      discovered in 1994, and it walks chronologically through the progress that has
      been made in understanding the biological function of this protein. Historically,
      Emp was the first identified cell attachment molecule and is expressed in both
      erythroblasts and macrophages and mediates their attachments to form
      erythroblastic islands. The absence of Emp erythroblasts shows defects in
      differentiation and enucleation. Emp-deficient macrophages display immature
      morphology characterized by small sizes, round shapes, and the lack of
      cytoplasmic projections. Although the primary sequence of Emp has already been
      determined and its role in both erythroid and macrophage development is well
      established, there are major gaps in the understanding of its function at the
      molecular level. Recent studies had implicated its importance in actin
      cytoskeleton remodeling and cell migration, but the molecular mechanisms are
      still enigmatic. Previous studies have also demonstrated that downregulation of
      Emp affects the expression of mitogen-associated protein kinase 1 (MAPK1) and
      thymoma viral protooncogene (AKT-1) resulting in abnormal cell motility. In this
      review, we summarize the proposed function of Emp based on previous studies,
      present scenarios, and its plausible future in translational research.

PMID- 29032608
TI  - MicroRNA profiling reveals dysregulated microRNAs and their target gene
      regulatory networks in cemento-ossifying fibroma.
AB  - BACKGROUND: Cemento-ossifying fibroma (COF) is a benign fibro-osseous neoplasm of
      uncertain pathogenesis, and its treatment results in morbidity. MicroRNAs (miRNA)
      are small non-coding RNAs that regulate gene expression and may represent
      therapeutic targets. The purpose of the study was to generate a comprehensive
      miRNA profile of COF compared to normal bone. Additionally, the most relevant
      pathways and target genes of differentially expressed miRNA were investigated by
      in silico analysis. METHODS: Nine COF and ten normal bone samples were included
      in the study. miRNA profiling was carried out by using TaqMan(r) OpenArray(r)
      Human microRNA panel containing 754 validated human miRNAs. We identified the
      most relevant miRNAs target genes through the leader gene approach, using STRING
      and Cytoscape software. Pathways enrichment analysis was performed using DIANA
      miRPath. RESULTS: Eleven miRNAs were downregulated (hsa-miR-95-3p, hsa-miR-141
      3p, hsa-miR-205-5p, hsa-miR-223-3p, hsa-miR-31-5p, hsa-miR-944, hsa-miR-200b-3p,
      hsa-miR-135b-5p, hsa-miR-31-3p, hsa-miR-223-5p and hsa-miR-200c-3p), and five
      were upregulated (hsa-miR-181a-5p, hsa-miR-181c-5p, hsa-miR-149-5p, hsa-miR-138
      5p and hsa-miR-199a-3p) in COF compared to normal bone. Eighteen common target
      genes were predicted, and the leader genes approach identified the following
      genes involved in human COF: EZH2, XIAP, MET and TGFBR1. According to the biology
      of bone and COF, the most relevant KEGG pathways revealed by enrichment analysis
      were proteoglycans in cancer, miRNAs in cancer, pathways in cancer, p53-, PI3K
      Akt-, FoxO- and TGF-beta signalling pathways, which were previously found to be
      differentially regulated in bone neoplasms, odontogenic tumours and osteogenesis.
      CONCLUSION: miRNA dysregulation occurs in COF, and EZH2, XIAP, MET and TGFBR1 are
      potential targets for functional analysis validation.

PMID- 29032609
TI  - Usefulness of endoscopic ultrasonography-elastography as a predictive tool for
      the occurrence of pancreatic fistula after pancreatoduodenectomy.
AB  - BACKGROUND: Pancreatic fistula (PF) is a major complication following
      pancreatoduodenectomy (PD). Pancreatic texture is a risk factor for PF, but its
      evaluation depends on the subjective judgment. The aim of this study was to
      investigate whether preoperative endoscopic ultrasonography-elastography (EUS
      EG), which objectively assesses tissue elasticity, predict the development of PF
      following PD. METHODS: Fifty-nine patients who underwent EUS-EG before PD and had
      pancreas parenchyma histologically evaluated were included. Using histogram
      analysis, mean elasticity (ME), which represents tissue elasticity and is
      inversely correlated with pancreatic fibrosis, was calculated. RESULTS: Among 59
      patients, 19 developed PF (32.2%). The ME in patients with PF was significantly
      higher than that in patients without PF (85.4 vs. 55.6, P < 0.001). Area under
      the receiver operating characteristic curve for the accuracy of pancreatic
      texture and ME for predicting PF were 0.718 and 0.846, respectively. When a ME of
      70.0 was used as a cut-off value for predicting PF, the sensitivity and
      specificity were 84.2% and 80.0%, respectively. In a multivariate logistic
      regression analysis, only a ME of >70.0 was an independent predictor of PF (odds
      ratio 10.02, P = 0.008). CONCLUSIONS: Endoscopic ultrasonography-elastography may
      be an accurate and objective method for predicting PF following PD.

PMID- 29032611
TI  - Fast IRMS screening of pseudoendogenous steroids in doping analyses.
AB  - The detection of the abuse of pseudoendogenous steroids (testosterone and/or its
      precursors) is currently based, when possible, on the application of the steroid
      module of the World Anti-Doping Agency (WADA), athlete biological passport (ABP),
      implemented through the global database, ADAMS. When a suspicious sample is
      detected, the confirmation by isotope ratio mass spectrometry (IRMS) is required.
      It is well known that this confirmation procedure is time consuming and expensive
      and can be only applied on a reduced number of samples. In previous studies we
      have demonstrated that the longitudinal evaluation of the IRMS data is able to
      detect positive samples that otherwise will be evaluated as negative, improving
      the efficacy of the fight against doping in sport. This would require the
      analysis of a much larger volume of samples by IRMS. The aim of the present work
      is to describe an IRMS screening method allowing to increase the throughput of
      samples that can be analyzed by IRMS. The detection efficacy of the method is
      compared with the confirmation method in use, and to assess its robustness and
      applicability, all the samples of a major cycling stage competition were
      analyzed, with the agreement of the testing authority, under routine conditions
      and response times. The results obtained permit to conclude that the IRMS
      screening method here proposed has adequate selectivity and produces results that
      overlap with the already validated method currently in use permitting to analyze
      a much higher volume of samples even during a major event without compromising
      the detection capacity. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 29032610
TI  - Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute
      cholangitis (with videos).
AB  - Although the diagnostic and severity grading criteria on the 2013 Tokyo
      Guidelines (TG13) are used worldwide as the primary standard for management of
      acute cholangitis (AC), they need to be validated through implementation and
      assessment in actual clinical practice. Here, we conduct a systematic review of
      the literature to validate the TG13 diagnostic and severity grading criteria for
      AC and propose TG18 criteria. While there is little evidence evaluating the TG13
      criteria, they were validated through a large-scale case series study in Japan
      and Taiwan. Analyzing big data from this study confirmed that the diagnostic rate
      of AC based on the TG13 diagnostic criteria was higher than that based on the
      TG07 criteria, and that 30-day mortality in patients with a higher severity based
      on the TG13 severity grading criteria was significantly higher. Furthermore, a
      comparison of patients treated with early or urgent biliary drainage versus
      patients not treated this way showed no difference in 30-day mortality among
      patients with Grade I or Grade III AC, but significantly lower 30-day mortality
      in patients with Grade II AC who were treated with early or urgent biliary
      drainage. This suggests that the TG13 severity grading criteria can be used to
      identify Grade II patients whose prognoses may be improved through biliary
      drainage. The TG13 severity grading criteria may therefore be useful as an
      indicator for biliary drainage as well as a predictive factor when assessing the
      patient's prognosis. The TG13 diagnostic and severity grading criteria for AC can
      provide results quickly, are minimally invasive for the patients, and are
      inexpensive. We recommend that the TG13 criteria be adopted in the TG18
      guidelines and used as standard practice in the clinical setting. Free full
      articles and mobile app of TG18 are available at:
      http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical
      questions and references are also included.

PMID- 29032613
TI  - Management of ventricular perforation during revascularization of an
      intramyocardial left anterior descending artery.
AB  - Ventricular perforation during exposure of an intramyocardial left anterior
      descending artery (LAD) in preparation for coronary artery bypass grafting is a
      known surgical complication. In this report, we discuss the management of this
      complication which avoids closure of the LAD and a myocardial infarction.

PMID- 29032612
TI  - Correlation between CXCR4/CXCR7/CXCL12 chemokine axis expression and prognosis in
      lymph-node-positive lung cancer patients.
AB  - The CXCR4/CXCR7/CXCL12 chemokine axis plays important roles in the migration of
      tumor cells during cancer development by modulating site-specific distant
      metastasis including to regional lymph nodes. We investigated the correlation of
      these chemokine expressions to prognosis in lymph-node-positive non-small-cell
      lung cancer (NSCLC) patients. A total of 140 surgically resected specimens of
      primary site (PS) and metastatic lymph nodes (MLN) of NSCLC involving hilar
      and/or mediastinal lymph nodes (N1-2) were collected. CXCR4, CXCR7 and CXCL12
      expressions were evaluated. Cox regression analysis was performed to determine
      whether these chemokines were independent prognostic factors in N1-2 NSCLC. High
      expression of CXCR4 in PS and CXCL12 in MLN was associated with poor overall
      survival (OS) (P = .025 and .033, respectively). Significant correlations between
      CXCR4 expression in PS and CXCL12 expression in MLN were observed (P = .040).
      There was significant difference in OS between 2 groups according to expressions
      of CXCR4 in PS and CXCL12 in MLN (P = .0033). Expression of CXCL12 in MLN was
      identified as an independent prognostic factor (HR 1.79, 95% CI 1.08-3.04, P =
      .023). CXCL12 in MLN was mainly expressed by tumor cells compared with stromal
      cells (56% vs 25%, respectively, P < .0001). CXCR4/CXCL12 may play roles in tumor
      progression in MLN and is associated with poor prognosis of lymph-node-positive
      NSCLC patients.

PMID- 29032614
TI  - Quantification of the effect of instrumentation error in objective gait
      assessment in the horse on hindlimb symmetry parameters.
AB  - BACKGROUND: Objective gait analysis is becoming more popular as a tool assisting
      veterinarians during the clinical lameness exam. At present, there is only
      limited information on the effect of misplacement of markers/motion-sensors.
      OBJECTIVES: To investigate and describe the effect of marker misplacement on
      commonly calculated pelvic symmetry parameters. STUDY DESIGN: Experimental study.
      METHODS: Each horse was equipped with custom-made devices consisting of several
      reflective markers arranged in a predefined manner with a reference marker
      correctly positioned regarding the anatomical landmark and several misplaced
      markers along the sagittal and transverse planes. Linear regression analysis was
      used to estimate the effect of marker misplacement. RESULTS: For the tubera
      sacrale, each cm of left/right misplacement led to a difference in minimum
      position of the pelvis (PDmin) of +/-1.67 mm (95% CI 1.54-1.8 mm) (P<0.001);
      maximum position of the pelvis (PDmax) was affected by +/-0.2 mm (95% CI 0.071
      0.33 mm) (P = 0.003). With respect to cranial/caudal misplacement, each cm of
      misplacement resulted in a PDmin difference of +/-0.04 mm (95% CI -0.09 to 0.16
      mm) (P = 0.56) and a PDmax difference of +/-0.008 mm (95% CI -0.13 to 0.12 mm) (P
      = 0.9). For the tubera coxae, each cm of vertical misplacement led to a
      difference in the displacement amplitude between left and right tubera coxae (Hip
      Hike_Diff) of +/-1.56 mm (95% CI 1.35-1.77 mm) (P<0.001); for the cranial/caudal
      misplacement, this was +/-0.82 mm (95% CI 0.66-0.97 mm) (P<0.001). MAIN
      LIMITATIONS: Only three horses were used in this experiment and the study design
      did not permit to determine the influence of marker misplacement on the
      evaluation of different degrees of lameness. CONCLUSIONS: Marker misplacement
      significantly affects calculated symmetry parameters of the pelvis. The observed
      errors are overall small but significant. In cases of mildly asymmetrical horses,
      this error might influence the decision-making process whereas in more severe
      asymmetries, the influence of the error effect may become less significant.

PMID- 29032615
TI  - Regulation of the prometastatic neuregulin-MMP13 axis by SRC family kinases:
      therapeutic implications.
AB  - Metastatic dissemination of tumor cells is responsible for the fatal outcome of
      breast cancer. Therefore, understanding the mechanisms involved in dissemination
      is essential for the development of new therapeutic strategies to prevent
      metastasis. One mechanism involved in metastatic dissemination of breast cancer
      cells is dependent on control of the production of matrix metalloproteinases by
      the neuregulins (NRGs). The NRGs are polypeptide factors that act by binding to
      the ErbB/HER subfamily of receptor tyrosine kinases. NRG-mediated activation of
      HER receptors causes an increase in the production of metalloprotease 13 (MMP13,
      also termed collagenase-3), which facilitates metastatic dissemination of breast
      tumors. In this context, we aimed to explore whether the clinically approved
      tyrosine kinase inhibitor dasatinib was able to neutralize this mechanism of
      metastatic dissemination. Here, we show that dasatinib restricted NRG-induced
      MMP13 upregulation, both in vitro and in vivo, and in vivo metastatic
      dissemination of breast cancer cells. Chemical proteomics studies showed that the
      main cellular targets of dasatinib were SRC family kinases (SFKs). Moreover,
      genetic studies showed that knockdown of SRC or YES strongly inhibited NRG
      induced MMP13 upregulation in vitro. Mechanistically, dasatinib treatment or
      knockdown of SRC also inhibited ERK1/2 kinases in vitro, which were required for
      NRG-induced MMP13 upregulation. These results open the possibility of clinically
      exploring the antitumoral action of dasatinib in those tumors in which the NRG
      MMP13 signaling axis may play a relevant role in the control of tumor cell
      dissemination.

PMID- 29032616
TI  - A survey on hematology-oncology pediatric AIEOP centres: The challenge of
      posterior reversible encephalopathy syndrome.
AB  - OBJECTIVES: Posterior reversible encephalopathy syndrome (PRES) is one of the
      most common neurological complications in hematology-oncology pediatric patients.
      Despite an increasingly recognized occurrence, no clear consensus exists
      regarding how best to manage the syndrome, because most cases of PRES have
      reported in single-case reports or small series. Aim of this paper is to identify
      incidence, clinical features, management, and outcome of PRES in a large series
      of hematology-oncology pediatric patients. METHODS: The cases of PRES occurred in
      twelve centers of the Italian Association of Pediatric Hematology and Oncology
      were reported. RESULTS: One hundred and twenty-four cases of PRES in 112
      pediatric patients were recorded with an incidence of 2.1% and 4.7%,
      respectively, in acute lymphoblastic leukemia in first complete remission and
      hematopoietic stem cell transplantation (HSCT). The majority of cases occurred
      after a cycle of chemotherapy rather than after stem cell transplant. PRES after
      chemotherapy significantly differs from that after HSCT for diagnosis, time of
      presentation, risk factors, management, and outcome. CONCLUSIONS: This study
      demonstrates that PRES is a common neurological complication and occurring
      preferentially in course of induction treatment of some hematologic malignancies,
      as ALL and after HSCT. It also highlights great clinical differences in the
      management and outcome in patients with PRES occurring after chemotherapy or
      after HSCT.

PMID- 29032617
TI  - Emerging issues in complementary feeding: Global aspects.
AB  - The complementary feeding period (6-24 months) is a window of opportunity for
      preventing stunting, wasting, overweight, and obesity and for improving long-term
      development and health. Because WHO published its guiding principles for
      complementary feeding in 2003, new knowledge and evidence have been generated in
      the area of child feeding. The aim of this paper is to highlight some of the
      emerging issues in complementary feeding and potential implications on the
      guidelines revision. Evidence on the effect of the quality and quantity of
      protein and fat intake on child growth during the complementary feeding period is
      summarized. The increased availability of sugar-containing beverages and
      unhealthy snack foods and its negative effect on young child's diet is described.
      Negative effects of nonresponsive feeding and force feeding are also discussed,
      although few scientific studies have addressed these issues. There are several
      emerging research areas that are likely to provide a better understanding of how
      complementary feeding influences growth, development, and health. These include
      the effect of the young child's diet on body composition, gastrointestinal
      microbiota, and environmental enteric dysfunction. However, at present, findings
      from these research areas are not likely to influence guidelines. Several
      emerging issues will be relevant to address when complementary feeding guidelines
      will be updated. With the increasing prevalence of obesity globally, it is
      important that guidelines on complementary feeding address both prevention of
      undernutrition and prevention of overweight, obesity, and noncommunicable
      diseases later in life.

PMID- 29032618
TI  - Scaling-up interventions to improve infant and young child feeding in India: What
      will it take?
AB  - We assessed India's readiness to deliver infant and young child feeding (IYCF)
      interventions by examining elements related to policy, implementation, financing,
      and evidence. We based our analysis on review of (a) nutrition policy guidance
      and program platforms, (b) published literature on interventions to improve IYCF
      in India, and (c) IYCF program models implemented between 2007 and 2012. We find
      that Indian policies are well aligned with global technical guidance on
      counselling interventions. However, guidelines for complementary food supplements
      (CFS) need to be reexamined. Two national programs with the operational
      infrastructure to deliver IYCF interventions offer great potential for scale, but
      more operational guidance, capacity, and monitoring are needed to actively
      support delivery of IYCF counselling at scale by available frontline workers.
      Many IYCF implementation efforts to date have experimented with approaches to
      improve breastfeeding and initiation of complementary feeding but not with
      improving diet diversity or the quality of food supplements. Financing is
      currently inadequate to deliver CFS at scale, and governance issues affect the
      quality and reach of CFS. Available evidence from Indian studies supports the use
      of counselling strategies to improve breastfeeding practices and initiation of
      complementary feeding, but limited evidence exists on improving full spectrum of
      IYCF practices and the impact and operational aspects of CFS in India. We
      conclude that India is well positioned to support the full spectrum of IYCF using
      existing policies and delivery platforms, but capacity, financing, and evidence
      gaps on critical areas of programming can limit impact at scale.

PMID- 29032619
TI  - First foods: Why improving young children's diets matter.
AB  - Globally, only 52% of children aged 6-23 months meet the minimum meal frequency
      and a mere 29% meet the minimum dietary diversity, with large disparities across
      and within regions. With most of the stunting occurring during the first thousand
      days-from conception to age 2 years-improving complementary feeding in children 6
      23 months old is an urgent priority. With this evidence in mind, UNICEF
      collaborated with the governments of India and Maharashtra to convene a global
      meeting in Mumbai, India, under the theme: First Foods: A Global Meeting to
      Accelerate Progress on Complementary Feeding in Young Children (November 17-18,
      2015). The global meeting provided a platform that aimed to (a) synthesize the
      biological and implementation science on complementary feeding; (b) review the
      practice and experience in improving access to nutritious complementary foods and
      good complementary feeding practices; and (c) consolidate a strong evidence base
      that can inform the development of strategies and approaches to improve
      complementary feeding that are fit to context. This overview paper summarizes the
      rationale on why improving complementary foods and feeding for infants and young
      children matters and what it takes to improve them. It builds on the papers
      presented at the First Foods Global Meeting and those commissioned as a follow on
      to it.

PMID- 29032620
TI  - Evaluation of programs to improve complementary feeding in infants and young
      children.
AB  - Evaluation of complementary feeding programs is needed to enhance knowledge on
      what works, to document responsible use of resources, and for advocacy.
      Evaluation is done during program conceptualization and design, implementation,
      and determination of effectiveness. This paper explains the role of evaluation in
      the advancement of complementary feeding programs, presenting concepts and
      methods and illustrating them through examples. Planning and investments for
      evaluations should occur from the beginning of the project life cycle. Essential
      to evaluation is articulation of a program theory on how change would occur and
      what program actions are required for change. Analysis of program impact pathways
      makes explicit the dynamic connections in the program theory and accounts for
      contextual factors that could influence program effectiveness. Evaluating
      implementation functioning is done through addressing questions about needs,
      coverage, provision, and utilization using information obtained from process
      evaluation, operations research, and monitoring. Evaluating effectiveness is done
      through assessing impact, efficiency, coverage, process, and causality.
      Plausibility designs ask whether the program seemed to have an effect above and
      beyond external influences, often using a nonrandomized control group and
      baseline and end line measures. Probability designs ask whether there was an
      effect using a randomized control group. Evaluations may not be able to use
      randomization, particularly for programs implemented at a large scale.
      Plausibility designs, innovative designs, or innovative combinations of designs
      sometimes are best able to provide useful information. Further work is needed to
      develop practical designs for evaluation of large-scale country programs on
      complementary feeding.

PMID- 29032621
TI  - Household food insecurity and children's dietary diversity and nutrition in
      India. Evidence from the comprehensive nutrition survey in Maharashtra.
AB  - We analyse data from the 2012 Comprehensive Nutrition Survey in the State of
      Maharashtra, India, which surveyed 2,630 households. This is a unique dataset
      because in addition to nutritional status of mothers and children, it has
      information on diets of women and children and household food security. This rich
      dataset allows us to address three issues: whether household food security
      predicts higher diet diversity in children aged 6-23 months; whether household
      food security predicts lower risk of undernutrition; and whether the lower risk
      of undernutrition in children who live in food secure households is mediated by
      improved diet diversity for children. We find that children from moderately food
      insecure and severely food insecure households are more likely to have lower diet
      diversity scores. We find that the odds of a child being severely stunted,
      severely underweight, or severely wasted are higher in severely food insecure
      households. After controlling for children's diet diversity, and other child,
      maternal and household characteristics, we find that household food security is
      no longer statistically associated with stunting, wasting, or underweight.
      However, diet diversity of children is statistically significantly associated
      with whether a child is stunted or underweight. Our results although not causal
      provide evidence for understanding the extent to which household food insecurity
      affects children's diet diversity and how both these factors affect nutrition
      outcomes in children. Our analysis informs Government of Maharashtra's and
      India's National Nutrition Mission in their efforts for formulating appropriate
      policies and programmes to address child undernutrition.

PMID- 29032622
TI  - Harnessing private sector expertise to improve complementary feeding within a
      regulatory framework: Where is the evidence?
AB  - Global recognition that the complex and multicausal problems of malnutrition
      require all players to collaborate and to invest towards the same objective has
      led to increased private sector engagement as exemplified through the Scaling Up
      Nutrition Business Network and mechanisms for blended financing and matched
      funding, such as the Global Nutrition for Growth Compact. The careful steps made
      over the past 5 to 10 years have however not taken away or reduced the hesitation
      and scepticism of the public sector actors towards commercial or even social
      businesses. Evidence of impact or even a positive contribution of a private
      sector approach to intermediate nutrition outcomes is still lacking. This
      commentary aims to discuss the multiple ways in which private sector can leverage
      its expertise to improve nutrition in general, and complementary feeding in
      particular. It draws on specific lessons learned in Bangladesh, Cote d'Ivoire,
      India, Indonesia, and Madagascar on how private sector expertise has contributed,
      within the boundaries of a regulatory framework, to improve availability,
      accessibility, affordability, and adequate use of nutritious foods. It concludes
      that a solid evidence base regarding the contribution of private sector to
      complementary feeding is still lacking and that the development of a systematic
      learning agenda is essential to make progress in the area of private sector
      engagement in nutrition.

PMID- 29032623
TI  - Complementary feeding practices: Current global and regional estimates.
AB  - Insufficient quantities and inadequate quality of complementary foods, together
      with poor feeding practices, pose a threat to children's health and nutrition.
      Interventions to improve complementary feeding are critical to reduce all forms
      of malnutrition, and access to data to ascertain the status of complementary
      feeding practices is essential for efforts to improve feeding behaviours.
      However, sufficient data to generate estimates for the core indicators covering
      the complementary feeding period only became available recently. The current
      situation of complementary feeding at the global and regional level is reported
      here using data contained within the UNICEF global database. Global rates of
      continued breastfeeding drop from 74.0% at 1 year of age to 46.3% at 2 years of
      age. Nearly a third of infants 4-5 months old are already fed solid foods,
      whereas nearly 20% of 10-11 months old had not consumed solid foods during the
      day prior to their survey. Of particular concern is the low rate (28.2%) of
      children 6-23 months receiving at least a minimally diverse diet. Although rates
      for all indicators vary by background characteristics, feeding behaviours are
      suboptimal even in richest households, suggesting that cultural factors and poor
      knowledge regarding an adequate diet for young children are important to address.
      In summary, far too few children are benefitting from minimum complementary
      feeding practices. Efforts are needed not only to improve children's diets for
      their survival, growth, and development but also for governments to report on
      progress against global infant and young child feeding indicators on a regular
      basis.

PMID- 29032624
TI  - Government information systems to monitor complementary feeding programs for
      young children.
AB  - Accelerating progress to improve complementary feeding of young children is a
      global priority. Strengthening monitoring through government information systems
      may increase the quality and implementation of infant and young child feeding
      (IYCF) programs. Monitoring is necessary for the effective implementation of
      programs as it allows program managers to assess program performance, identify
      problems, and take corrective action. Program descriptions and conceptual models
      explain how program inputs and activities should lead to outputs and outcomes,
      and ultimately public health impact; thus, they are critical tools when designing
      effective IYCF programs and monitoring systems as these descriptions and
      conceptual models form the basis for the program and are key for developing the
      monitoring system, indicators, and tools. Despite their importance, many programs
      do not have these documented, nor monitoring plans, limiting their ability to
      design effective programs and monitoring systems. Once in place, it is important
      to periodically review the monitoring system to confirm it still appropriately
      meets stakeholder needs and the data are being used to inform decision-making,
      and to make program adjustments as the monitoring focus, resources, or capacity
      may change during the program lifecycle. Including priority indicators of IYCF
      practices and counseling indicators in the government information systems may
      strengthen IYCF programs when the indicators are contextualized to the government
      IYCF program, capacity, and setting, and the indicators are used for decision
      making and program improvement.

PMID- 29032625
TI  - The potential role of micronutrient powders to improve complementary feeding
      practices.
AB  - Micronutrient powder (MNP) interventions are often integrated within infant and
      young child feeding (IYCF) programmes to improve micronutrient intake from
      complementary foods. This review aims to describe country experiences with MNP
      interventions and their impact on IYCF practices and develop a framework for how
      MNP may strengthen complementary feeding practices. A literature review and key
      informant interviews were used to gather data on complementary feeding practices
      in MNP programme design, implementation, and evaluation. Findings from 11 MNP
      programmes in different geographic regions reinforced the potential of MNP
      interventions to add renewed focus and resources to existing IYCF programmes. MNP
      plays an important role in ensuring adequate micronutrient intake and reducing
      anaemia in young children. In some programmes, MNP users had improved IYCF
      practices, such as breastfeeding to 24 months and children receiving
      complementary foods with adequate consistency, frequency, and diversity. Our
      framework highlights how behaviour change communication is an essential component
      for influencing household actions, not only to generate demand and promote
      correct and sustained MNP use but also raise awareness of IYCF practices. The
      actions at MNP policy, delivery, and behaviour change communication levels
      collectively influence household IYCF practices, and formative research and
      monitoring and evaluation serve to inform programme design and optimize impact.
      In conclusion, a limited but growing body of evidence suggests that MNP
      interventions can contribute to improve complementary feeding practices. However,
      there is scope for improvement even among integrated MNP and IYCF programmes in
      order to realize the full potential of MNP interventions for IYCF practices.

PMID- 29032626
TI  - Using behavior change approaches to improve complementary feeding practices.
AB  - This paper applies an implementation framework, based on a behavior change model,
      to compare four case studies of complementary feeding programs. It aims to expand
      our understanding of how to design and implement behavior change interventions
      aimed at improving complementary feeding practices. Four programs met the
      selection criteria of scale and documented improvements: Bangladesh, Malawi,
      Peru, and Zambia. We examined commonalities and differences in the design and
      implementation of social and behavior change approaches, use of program delivery
      platforms, challenges encountered, and lessons learned. We conclude that
      complementary feeding practices, in particular dietary diversity, can be improved
      rapidly in a variety of settings using available program platforms if
      interventions focus on specific constraints to food access and use effective
      strategies to encourage caregivers to prepare and feed appropriate foods. A five
      step process is presented that can be applied across a range of complementary
      feeding programs to strengthen their impacts.

PMID- 29032627
TI  - Complementary feeding practices for infants and young children in South Asia. A
      review of evidence for action post-2015.
AB  - Some 37% (~64 million) South Asian children under 5 years are stunted. Most
      stunting occurs during the complementary feeding period (6-23 months). Our
      objective was to (a) characterize complementary feeding practices in South Asia
      and (b) review the effectiveness of information, education, and counselling (IEC)
      interventions aiming to improve complementary feeding in South Asia. We conducted
      a comprehensive review of (a) the latest nationally representative survey data
      and (b) peer-reviewed interventions (January 1990 to December 2015) that used IEC
      as the main strategy to improve complementary feeding. The analytical sample
      included 30,966 children aged 6-23 months. Foods made from grains are the main
      complementary food (76.8% of children). Only 33.2% of children are fed fruits and
      vegetables rich in vitamin A and a mere 17.1% are fed complementary foods
      containing meat, fish, poultry and/or eggs. Timely introduction, minimum meal
      frequency, minimum dietary diversity, and minimum acceptable diet were estimated
      at 57.4%, 47.7%, 33.0%, and 20.5%, respectively. The evidence on the
      effectiveness of IEC interventions is limited in quantity, quality, and scale.
      The 12 intervention studies that met the inclusion criteria indicate that IEC
      interventions delivered by many types of primary care workers/community resource
      persons using multiple contact opportunities improved the timeliness, frequency,
      diversity, and/or adequacy of complementary feeding. However, acceptability,
      availability, and affordability seem to constrain improvements in diet diversity,
      particularly foods of animal origin. The small size of most intervention studies
      and the training and/or supervision intensity of counsellors raise concerns about
      the potential for scale and/or sustainability of some of the interventions
      reviewed.

PMID- 29032628
TI  - Diet quality and risk of stunting among infants and young children in low- and
      middle-income countries.
AB  - Age-appropriate complementary feeding practices are far from optimal among low-
      and middle-income countries with available data. The evidence on the association
      between feeding practices and linear growth is mixed. We sought to systematically
      examine the association between two indictors of dietary quality-dietary
      diversity and animal source food (ASF) consumption (WHO, 2008)-and stunting
      (length-for-age z-score) employing existing data from 39 Demographic and Health
      Surveys. Data on 74,548 children aged 6-23 months were pooled and multiple
      logistic regression models, adjusting for child, maternal, and household
      characteristics, employed to assess the association between dietary quality and
      stunting. Stratified models by child age and by World Bank country-income
      classifications (World Bank, 2015) were also applied. Children aged 6-23 months
      consuming zero food groups in the previous day had a 1.345 higher odds of being
      stunted when compared to the reference group (>=5 food groups); those who did not
      consume any ASF in the previous day had a 1.436 higher odds of being stunted
      compared to children consuming all three types of ASF (egg, meat, and dairy). We
      estimated that 2,629 cases of stunting would have been averted (12.6% of those
      stunted) among the population studied if all children had consumed five or more
      food groups. Outcomes by country-income groupings showed larger associations of
      diet diversity and ASF consumption for upper- and lower-middle income countries
      compared to low-income countries. In summary, dietary diversity and ASF
      consumption were associated with stunting, with associations varying by
      stratified groups.

PMID- 29032629
TI  - Consumption of commercially produced snack foods and sugar-sweetened beverages
      during the complementary feeding period in four African and Asian urban contexts.
AB  - The availability and consumption of commercially produced foods and beverages
      have increased across low-income and middle-income countries. This cross
      sectional survey assessed consumption of commercially produced foods and
      beverages among children 6-23 months of age, and mothers' exposure to promotions
      for these products. Health facility-based interviews were conducted among 218
      randomly sampled mothers utilizing child health services in Dakar, Senegal; 229
      in Dar es Salaam, Tanzania; 228 in Kathmandu Valley, Nepal; and 222 in Phnom
      Penh, Cambodia. In the day prior to the interview, 58.7% of 6-23-month-olds in
      Dakar, 23.1% in Dar es Salaam, 74.1% in Kathmandu Valley, and 55.0% in Phnom Penh
      had consumed a commercially produced snack food. In the previous week, the
      majority of children in Dakar (79.8%), Kathmandu Valley (91.2%), and Phnom Penh
      (80.6%) had consumed such products. Consumption of commercially produced sugar
      sweetened beverages was noted among 32.0% of Phnom Penh, 29.8% of Dakar, 23.1% of
      Dar es Salaam, and 16.2% of Kathmandu Valley children. Maternal education was
      negatively associated with commercial snack food consumption in Dakar and
      Kathmandu Valley. Children of Phnom Penh mothers in the lowest wealth tercile
      were 1.5 times more likely to consume commercial snack food products, compared to
      wealthier mothers. These snack consumption patterns during the critical
      complementary feeding period demand attention; such products are often high in
      added sugars and salt, making them inappropriate for infants and young children.

PMID- 29032630
TI  - Risk factors of poor complementary feeding practices in Pakistani children aged 6
      23 months: A multilevel analysis of the Demographic and Health Survey 2012-2013.
AB  - Appropriate feeding practices are crucial for survival, growth, and development
      in childhood. This paper analyzes Pakistan's Demographic and Health Survey 2012
      2013 to fill the knowledge gap in risk factors of poor complementary feeding
      practices in Pakistani children. Multilevel models were applied to fit the
      multistage cluster sample of 2,827 children aged 6-23 months from 489
      communities. Introduction of solid, semi-solid, or soft foods (intro) was
      achieved in 67% infants aged 6-8 months. Among children aged 6-23 months, the
      proportion of children meeting minimum meal frequency, dietary diversity (MDD),
      and acceptable diet criteria were 63%, 22% and 15%, respectively. Consumption of
      legumes and nuts, flesh foods, and vitamin A-rich fruits and vegetables was low
      in all children (6-19%), even among children who met the MDD criteria (15-55%).
      Younger child age, especially between 6 and 11 months and delayed maternal
      postnatal checkup were significant individual-level risk factors that
      consistently increased the odds of not meeting all four criteria examined. Fewer
      antenatal care visits predicted the odds of achieving intro and minimum meal
      frequency while younger maternal age and household poverty predicted the odds of
      achieving MDD and minimum acceptable diet. Community-level factors included
      geographic region and general access to maternal and child health care services.
      The overall poor quality of children's complementary diets in Pakistani calls for
      stronger policy and program action to promote the consumption of key nutrient
      dense foods while prioritizing interventions for the most vulnerable children and
      populations.

PMID- 29032631
TI  - Tools to improve planning, implementation, monitoring, and evaluation of
      complementary feeding programmes.
AB  - Adequate nutrient intake is a prerequisite for achieving good nutrition status.
      Suboptimal complementary feeding practices are a main risk factor for stunting.
      The need for systematic and user-friendly tools to guide the planning,
      implementation, monitoring, and evaluation of dietary interventions for children
      aged 6-23 months has been recognized. This paper describes five tools, namely,
      ProPAN, Optifood, Cost of the Diet, Fill the Nutrient Gap, and Monitoring Results
      for Equity System that can be used in different combinations to improve situation
      analysis, planning, implementation, monitoring, or evaluation approaches for
      complementary feeding in a particular context. ProPAN helps with development of
      strategies and activities designed to change the behaviours of the target
      population. Optifood provides guidance for developing food-based recommendations.
      The Cost of the Diet can provide insight on economic barriers to accessing a
      nutritious and balanced diet. The Fill the Nutrient Gap facilitates formulation
      of context-specific policies and programmatic approaches to improve nutrient
      intake, through a multistakeholder process that uses insights from linear
      programming and secondary data. The Monitoring Results for Equity System helps
      with analysis of gaps, constraints, and determinants of complementary feeding
      interventions and adoption of recommended practices especially in the most
      vulnerable and deprived populations. These tools, and support for their use, are
      readily available and can be used either alone and/or complementarily throughout
      the programme cycle to improve infant and young child-feeding programmes at
      subnational and national levels.

PMID- 29032633
TI  - 2017 Annual Meetings.

PMID- 29032632
TI  - Linking agriculture and nutrition education to improve infant and young child
      feeding: Lessons for future programmes.
AB  - Agriculture and food systems play a central role in nutrition by supplying
      nutritious, healthy and affordable foods. When integrated with nutrition
      education for behaviour change, agricultural interventions that supply diverse
      affordable foods from all food groups have great scope for improving young child
      and family diets. In 2014, process reviews were conducted in Cambodia and Malawi
      of food security projects that provided agricultural support and community-based
      nutrition education on improved infant and young child feeding (IYCF). In both
      countries, household visits were carried out with mothers/caregivers, and
      interviews and Focus Group Discussions (FGDs) were conducted with purposively
      selected project stakeholders (53 in Cambodia, 170 in Malawi), including
      government staff from the agriculture and health sectors. Results highlight that
      adoption of improved IYCF practices was facilitated by participation in nutrition
      education and practical cooking sessions, and supportive family and community
      structures. Barriers faced by families and caregivers were identified, such as
      women's workload and lack of access to high quality foods, namely fruits,
      vegetables, legumes, nuts and animal source foods. Implementation challenges
      regarding coordination of cross-sectoral targeting strategies and capacities of
      extension services to sustain community-based IYCF nutrition education need to be
      addressed to improve programme effectiveness and impact. The project lessons from
      Cambodia and Malawi are useful for integrated agriculture-IYCF nutrition
      education programmes to help ensure better young child nutrition outcomes.

PMID- 29032634
TI  - Prevalence of hepatitis C infection and its associated factors in healthy adults
      without identifiable route of transmission.
AB  - While hepatitis C virus (HCV) infection is long known to be associated with
      parenteral exposure, the specific route of transmission is not identified in a
      proportion of infected patients. Taking blood donors as the surrogate of healthy
      adults in the community in Hong Kong, we identified 91 HCV-infected donors
      (<=0.02% positive rate) in 2014-2016, of whom 46 were recruited in a mixed-method
      study to examine their transmission routes. A majority (75%) of the recruited
      donors were HCV RNA positive, with the predominant subtypes being 1b and 6a. From
      the results of the structured self-administered questionnaire and in-depth
      interviews, only 14 (30%) recruited donors could be traced to past history of
      contaminated blood transfusion (n = 9) or injection drug use (n = 5). Case
      control analyses with 3 different control groups were performed to examine
      factors associated with HCV infection in multivariable analyses. High-risk sexual
      behaviour, body piercing, intramuscular injection and vaccine inoculation abroad,
      having lived abroad for >3 months were significantly associated with HCV in
      donors with otherwise nonidentifiable source of infection. While the specific
      route of transmission cannot be established for each person, associations with
      multiple parenteral exposures outside Hong Kong were observed. The World Health
      Organization has advocated for the global elimination of HCV by 2030. With a high
      proportion of HCV-infected persons who are unaware of their infections, HCV
      elimination could be hard to achieve.

PMID- 29032635
TI  - Prevalence and natural course of occult hepatitis B virus infection in residents
      of 2 communities of Wuwei City, Gansu Province, China.
AB  - Occult hepatitis B infection (OBI) is characterized by serum hepatitis B surface
      antigen (HBsAg) negative and hepatitis B virus (HBV) DNA positive (HBsAg-/HBV
      DNA+). Occult hepatitis B infection in community-based populations has been
      scarcely investigated, and OBI outcomes remain unclear, especially in Wuwei, a
      region located in Northwest China. This region is one of the areas in China that
      has the highest prevalence of chronic HBV infection. A prospective study was
      performed in the general population of 2 towns of Wuwei from June 2011 to May
      2014. A questionnaire was used to collect demographic and medical data, and serum
      samples were collected from the participants and stored until analysis. DNA was
      detected using quantitative PCR (qPCR) or nested PCR, the HBV DNA from HBV DNA
      positive or possible positive (below the detection limit) subjects was extracted
      and amplified by nested PCR, and the PCR products were sequenced. Sequence
      analysis was performed using the Mega 6.0 program and CLC sequence viewer
      software. Hepatitis B virus DNA was detected in 90 of 3,080 HBsAg-negative
      subjects, and the prevalence of OBI in the study population was 2.92% (90/3,080,
      95% CI: 2.33%-3.51%). Hepatitis B virus genomes in 51 of 80 objects (63.75%)
      contained mutations in the "a" determinant of HBsAg. After 2 years follow-up, 42
      of 90 HBV DNA of OBI subjects remained positive, and the natural clearance rate
      of OBI subjects was 53.3%. Occult hepatitis B infection prevalence in this cohort
      was much lower than chronic HBV infection in the same region. HBV DNA was cleared
      in most OBI subjects during the 2 year period. Our data suggest that some OBI may
      represent a late stage of resolving the HBV infection process.

PMID- 29032637
TI  - Electron-Proton Transfer Mechanism of Excited-State Hydrogen Transfer in Phenol
      (NH3 )n (n=3 and 5).
AB  - Excited-state hydrogen transfer (ESHT) is responsible for various photochemical
      processes of aromatics, including photoprotection of nuclear basis. Its mechanism
      is explained by internal conversion from the aromatic pipi* to pisigma* states
      via conical intersection. This means that the electron is transferred to a
      diffuse Rydberg-like sigma* orbital apart from proton migration. This picture
      means the electron and the proton do not move together and the dynamics are
      different in principle. Here, we have applied picosecond time-resolved near
      infrared (NIR) and infrared (IR) spectroscopy to the phenol-(NH3 )5 cluster, the
      benchmark system of ESHT, and monitored the electron transfer and proton motion
      independently. The electron transfer monitored by the NIR transition rises within
      3 ps, while the overall H transfer detected by the IR absorption of NH vibration
      appears with a lifetime of about 20 ps. This clearly proves that the electron
      motion and proton migration are decoupled. Such a difference of the time
      evolutions between the NIR absorption and the IR transition has not been detected
      in a cluster with three ammonia molecules. We will report our full observation
      together with theoretical calculations of the potential energy surfaces of the
      pipi* and pisigma* states, and will discuss the ESHT mechanism and its cluster
      size-dependence between n=3 and 5. It is suggested that the presence and absence
      of a barrier in the proton transfer coordinate cause the different dynamics.

PMID- 29032636
TI  - Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute
      cholecystitis (with videos).
AB  - The Tokyo Guidelines 2013 (TG13) for acute cholangitis and cholecystitis were
      globally disseminated and various clinical studies about the management of acute
      cholecystitis were reported by many researchers and clinicians from all over the
      world. The 1st edition of the Tokyo Guidelines 2007 (TG07) was revised in 2013.
      According to that revision, the TG13 diagnostic criteria of acute cholecystitis
      provided better specificity and higher diagnostic accuracy. Thorough our
      literature search about diagnostic criteria for acute cholecystitis, new and
      strong evidence that had been released from 2013 to 2017 was not found with
      serious and important issues about using TG13 diagnostic criteria of acute
      cholecystitis. On the other hand, the TG13 severity grading for acute
      cholecystitis has been validated in numerous studies. As a result of these
      reviews, the TG13 severity grading for acute cholecystitis was significantly
      associated with parameters including 30-day overall mortality, length of hospital
      stay, conversion rates to open surgery, and medical costs. In terms of severity
      assessment, breakthrough and intensive literature for revising severity grading
      was not reported. Consequently, TG13 diagnostic criteria and severity grading
      were judged from numerous validation studies as useful indicators in clinical
      practice and adopted as TG18/TG13 diagnostic criteria and severity grading of
      acute cholecystitis without any modification. Free full articles and mobile app
      of TG18 are available at:
      http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical
      questions and references are also included.

PMID- 29032638
TI  - Sodium-glucose cotransporter 2 inhibitor, tofogliflozin, shows better
      improvements of blood glucose and insulin secretion in patients with high insulin
      levels at baseline.
AB  - AIMS/INTRODUCTION: Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new
      class of drugs for the treatment of type 2 diabetes mellitus that improve control
      of plasma glucose and bodyweight, giving great hope for the clinical utility of
      these agents. However, it is unclear for which patients SGLT2 inhibitors will be
      useful. MATERIALS AND METHODS: We analyzed data from long-term tofogliflozin
      monotherapy in an open-label, randomized controlled trial in Japanese patients
      with type 2 diabetes mellitus. Patients were divided into tertiles by baseline
      insulin level: group low (L): insulin <=5.6 MUU/mL, group medium (M): 5.6<
      insulin <=10 MUU/mL and group high (H): insulin >10 MUU/mL. RESULTS: Glycated
      hemoglobin and fasting plasma glucose levels, along with bodyweight, were
      significantly reduced from the baseline in all groups. The changes in levels of
      plasma glucose area under the curve for 2 h, C-peptide index area under the curve
      for 2 h during the meal tolerance tests and the insulin secretion index were the
      largest in the H group. The incidence of drug-related adverse events was not
      different among the three groups. DISCUSSION: Although tofogliflozin was
      effective regardless of baseline insulin level, it showed the highest efficacy in
      the H group.

PMID- 29032639
TI  - Long-term mental wellbeing of adolescents and young adults diagnosed with venous
      thromboembolism: results from a multistage mixed methods study.
AB  - : Essentials Long-term mental wellbeing of adolescents and young adults with
      venous thromboembolism is unclear. This multistage mixed methods study was based
      on Danish nationwide registry data and interviews. Mental wellbeing is negatively
      impacted in the long-term and uncertainty of recurrence is pivotal. The perceived
      health threat is more important than disease severity for long-term mental
      wellbeing. SUMMARY: Background Critical and chronic illness in youth can lead to
      impaired mental wellbeing. Venous thromboembolism (VTE) is a potentially
      traumatic and life-threatening condition. Nonetheless, the long-term mental
      wellbeing of adolescents and young adults (AYAS) with VTE is unclear. Objectives
      To investigate the long-term mental wellbeing of AYAS (aged 13-33 years)
      diagnosed with VTE. Methods We performed a multistage mixed method study based on
      data from the Danish nationwide health registries, and semistructured interviews
      with 12 AYAS diagnosed with VTE. An integrated mixed methods interpretation of
      the findings was conducted through narrative weaving and joint displays. Results
      The integrated mixed methods interpretation showed that the mental wellbeing of
      AYAS with VTE had a chronic perspective, with a persistently higher risk of
      psychotropic drug purchase among AYAS with a first-time diagnosis of VTE than
      among sex-matched and age-matched population controls and AYAS with a first-time
      diagnosis of insulin-dependent diabetes mellitus. Impaired mental wellbeing was
      largely connected to a fear of recurrence and concomitant uncertainty. Therefore,
      it was important for the long-term mental wellbeing to navigate uncertainty. The
      perceived health threat played a more profound role in long-term mental wellbeing
      than disease severity, as the potential life threat was the pivot which pointed
      back to the initial VTE and forward to the perception of future health threat and
      the potential risk of dying of a recurrent event. Conclusion Our findings show
      that the long-term mental wellbeing of AYAS diagnosed with VTE is negatively
      affected, and highlights these patients' need for adequate support.

PMID- 29032640
TI  - Deciphering Diversity Indices for a Better Understanding of Microbial
      Communities.
AB  - The past decades have been a golden era during which great tasks were
      accomplished in the field of microbiology, including food microbiology. In the
      past, culture-dependent methods have been the primary choice to investigate
      bacterial diversity. However, using cultureindependent high-throughput sequencing
      of 16S rRNA genes has greatly facilitated studies exploring the microbial
      compositions and dynamics associated with health and diseases. These culture
      independent DNA-based studies generate large-scale data sets that describe the
      microbial composition of a certain niche. Consequently, understanding microbial
      diversity becomes of greater importance when investigating the composition,
      function, and dynamics of the microbiota associated with health and diseases.
      Even though there is no general agreement on which diversity index is the best to
      use, diversity indices have been used to compare the diversity among samples and
      between treatments with controls. Tools such as the Shannon- Weaver index and
      Simpson index can be used to describe population diversity in samples. The
      purpose of this review is to explain the principles of diversity indices, such as
      Shannon- Weaver and Simpson, to aid general microbiologists in better
      understanding bacterial communities. In this review, important questions
      concerning microbial diversity are addressed. Information from this review should
      facilitate evidence-based strategies to explore microbial communities.

PMID- 29032641
TI  - Cholic Acid Attenuates ER Stress-Induced Cell Death in Coxsackievirus-B3
      Infection.
AB  - Coxsackievirus Type B3 (CVB3) is an enterovirus that belongs to the
      Picornaviridae and causes various diseases such as myocarditis and hand-foot
      mouth disease. However, an effective antiviral drug is still not developed. In
      this study, we looked for potential inhibitors of CVB3 replication by examining
      the survival of CVB3-infected HeLa cells. We detected an antiviral effect by
      cholic acid and identified it as a candidate inhibitor of CVB3 replication.
      Cholic acid circulates in the liver and intestines, and it helps the digestion
      and absorption of lipids in the small intestine. HeLa cells were cultured in 12
      well plates and treated with cholic acid (1 and 10 MUg/ml) and 106 PFU/ml of
      CVB3. After 16 h post-infection, the cells were lysed and subjected to western
      blot analysis and RT-PCR. The production of the viral capsid protein VP1 was
      dramatically decreased, and translation initiation factor eIF4G1 cleavage was
      significantly inhibited by treatment with 10 MUg/ml cholic acid. Moreover, cholic
      acid inhibited ERK signaling in CVB3-infected HeLa cells. RT-PCR showed that the
      amounts of the CVB3 RNA genome and mRNA for the ER stress-related transcription
      factor ATF4 were significantly reduced. These results showed that cholic acid
      strongly reduced ER stress and CVB3 proliferation. This compound can be developed
      as a safe natural therapeutic agent for enterovirus infections.

PMID- 29032642
TI  - Characterization of ATPase Activity of Free and Immobilized Chromatophore
      Membrane Vesicles of Rhodobacter sphaeroides.
AB  - The intracytoplasmic membrane of Rhodobacter sphaeroides readily vesiculates when
      cells are lysed. The resulting chromatophore membrane vesicle (CMV) contains the
      photosynthetic machineries to synthesize ATP by ATPase. The light-dependent
      ATPase activity of CMV was lowered in the presence of O2, but the activity
      increased to the level observed under anaerobic condition when the reaction
      mixture was supplemented with ascorbic acid (>=0.5 mM). Cell lysis in the
      presence of biotinyl cap phospholipid (bcp) resulted in the incorporation of bcp
      into the membrane to form biotinylated CMV (bCMV), which binds to streptavidin
      resin at a ratio of approximately 24 MUg bacteriochlorophyll a/ml resin. The
      ATPase activity of CMV was not affected by biotinylation, but approximately 30%
      of the activity was lost by immobilization to resin. Interestingly, the remaining
      70% of ATPase activity stayed constant during 7-day storage at 4 degrees C. On
      the contrary, the ATPase activity of bCMV without immobilization gradually
      decreased to approximately 40% of the initial level in the same comparison. Thus,
      the ATPase activity of CMV is sustainable after immobilization, and the
      immobilized bCMV can be used repeatedly as an ATP generator.

PMID- 29032643
TI  - Effects of Extended Storage of Chlorhexidine Gluconate and Benzalkonium Chloride
      Solutions on the Viability of Burkholderia cenocepacia.
AB  - Chlorhexidine gluconate (CHX) and benzalkonium chloride (BZK) formulations are
      frequently used as antiseptics in healthcare and consumer products. Burkholderia
      cepacia complex (BCC) contamination of pharmaceutical products could be due to
      the use of contaminated water in the manufacturing process, over-diluted
      antiseptic solutions in the product, and the use of outdated products, which in
      turn reduces the antimicrobial activity of CHX and BZK. To establish a "safe use"
      period following opening containers of CHX and BZK, we measured the antimicrobial
      effects of CHX (2-10 MUg/ml) and BZK (10-50 MUg/ml) at sublethal concentrations
      on six strains of Burkholderia cenocepacia using chemical and microbiological
      assays. CHX (2, 4, and 10 MUg/ml) and BZK (10, 20, and 50 MUg/ml) stored for 42
      days at 23 degrees C showed almost the same concentration and toxicity compared
      with freshly prepared CHX and BZK on B. cenocepacia strains. When 5 MUg/ml CHX
      and 20 MUg/ml BZK were spiked to six B. cenocepacia strains with different
      inoculum sizes (100 -105 CFU/ml), their toxic effects were not changed for 28
      days. B. cenocepacia strains in diluted CHX and BZK were detectable at
      concentrations up to 102 CFU/ml after incubation for 28 days at 23 degrees C.
      Although abiotic and biotic changes in the toxicity of both antiseptics were not
      observed, our results indicate that B. cenocepacia strains could remain viable in
      CHX and BZK for 28 days, which in turn, indicates the importance of control
      measures to monitor BCC contamination in pharmaceutical products.

PMID- 29032644
TI  - Characterization of Bacterial Community Dynamics during the Decomposition of Pig
      Carcasses in Simulated Soil Burial and Composting Systems.
AB  - Soil burial is the most widely used disposal method for infected pig carcasses,
      but composting has gained attention as an alternative disposal method because pig
      carcasses can be decomposed rapidly and safely by composting. To understand the
      pig carcass decomposition process in soil burial and by composting, pilot-scale
      test systems that simulated soil burial and composting were designed and
      constructed in the field. The envelope material samples were collected using
      special sampling devices without disturbance, and bacterial community dynamics
      were analyzed by high-throughput pyrosequencing for 340 days. Based on the odor
      gas intensity profiles, it was estimated that the active and advanced decay
      stages were reached earlier by composting than by soil burial. The dominant
      bacterial communities in the soil were aerobic and/or facultatively anaerobic
      gram-negative bacteria such as Pseudomonas, Gelidibacter, Mucilaginibacter, and
      Brevundimonas. However, the dominant bacteria in the composting system were
      anaerobic, thermophilic, endospore-forming, and/or halophilic gram-positive
      bacteria such as Pelotomaculum, Lentibacillus, Clostridium, and Caldicoprobacter.
      Different dominant bacteria played important roles in the decomposition of pig
      carcasses in the soil and compost. This study provides useful comparative date
      for the degradation of pig carcasses in the soil burial and composting systems.

PMID- 29032645
TI  - L-Glycine Alleviates Furfural-Induced Growth Inhibition during Isobutanol
      Production in Escherichia coli.
AB  - Lignocellulose is now a promising raw material for biofuel production. However,
      the lignin complex and crystalline cellulose require pretreatment steps for
      breakdown of the crystalline structure of cellulose for the generation of
      fermentable sugars. Moreover, several fermentation inhibitors are generated with
      sugar compounds, majorly furfural. The mitigation of these inhibitors is required
      for the further fermentation steps to proceed. Amino acids were investigated on
      furfural-induced growth inhibition in E. coli producing isobutanol. Glycine and
      serine were the most effective compounds against furfural. In minimal media,
      glycine conferred tolerance against furfural. From the IC50 value for inhibitors
      in the production media, only glycine could alleviate growth arrest for furfural,
      where 6 mM glycine addition led to a slight increase in growth rate and
      isobutanol production from 2.6 to 2.8 g/l under furfural stress. Overexpression
      of glycine pathway genes did not lead to alleviation. However, addition of
      glycine to engineered strains blocked the growth arrest and increased the
      isobutanol production about 2.3-fold.

PMID- 29032646
TI  - Soluble Prokaryotic Expression and Purification of Bioactive Tumor Necrosis
      Factor-Related Apoptosis-Inducing Ligand.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered as
      an antitumor agent owing to its ability to induce apoptosis of cancer cells
      without imparting toxicity toward most normal cells. TRAIL is produced in poor
      yield because of its insoluble expression in the cytoplasm of E. coli. In this
      study, we achieved soluble expression of TRAIL by fusing maltose-binding protein
      (MBP), b'a' domain of protein disulfide isomerase (PDIb'a'), or protein disulfide
      isomerase at the N-terminus of TRAIL. The TRAIL was purified using subsequent
      immobilized metal affinity chromatography and amylose-binding chromatography,
      with the tag removal using tobacco etch virus protease. Approximately 4.5 mg of
      pure TRAIL was produced from 125 ml flask culture with a purification yield of
      71.6%. The endotoxin level of the final product was 0.4 EU/MUg, as measured by
      the Limulus amebocyte lysate endotoxin assay. The purified TRAIL was validated
      and shown to cause apoptosis of HeLa cells with an EC50 and Hill coefficient of
      0.6 +/- 0.03 nM and 2.41 +/- 0.15, respectively. The high level of apoptosis in
      HeLa cells following administration of purified TRAIL indicates the significance
      and novelty of this method for producing high-grade and high-yield TRAIL.

PMID- 29032647
TI  - Development of Cabbage Juice Medium for Industrial Production of Leuconostoc
      mesenteroides Starter.
AB  - Leuconostoc mesenteroides is used as a starter to produce high-quality kimchi
      products. In this study, an efficient and economical cabbage juice medium (CJM)
      was developed by process optimization of cabbage extraction and pasteurization
      and by compositional supplementation of various lacking nutrients. The
      pasteurized cabbage juice was determined to be a good medium candidate to
      cultivate L. mesenteroides, showing maximal cell numbers (9.85 * 108CFU/ml) after
      24 h. Addition of sucrose and yeast extract with soy peptone resulted in
      increment of bacterial cell counts in CJM, showing the supplementing effect of
      the lacking nutrients. Furthermore, addition of shell powder gave a protective
      effect on bacterial cells by preventing pH decline and organic acid accumulation
      in CJM, resulting in a 2-fold increase of bacterial counts. The optimized
      composition of CJM was 70% cabbage juice diluted with water, 0.5% (w/v) sucrose,
      1% (w/v) yeast extract, 1% (w/v) soy peptone, and 1.5% (w/v) ark shell powder.
      The CJM developed in this study was able to yield a comparable level of bacterial
      counts with MRS medium and reduced the cost by almost 10-fold.

PMID- 29032648
TI  - Kaposi's Sarcoma-Associated Herpesvirus Infection Modulates the Proliferation of
      Glioma Stem-Like Cells.
AB  - Glioblastoma multiforme is the most lethal malignant brain tumor. Despite many
      intensive studies, the prognosis of glioblastoma multiforme is currently very
      poor, with a median overall survival duration of 14 months and 2-year survival
      rates of less than 10%. Although viral infections have been emphasized as
      potential cofactors, their influences on pathways that support glioblastoma
      progression are not known. Some previous studies indicated that human Kaposi's
      sarcoma-associated herpesvirus (KSHV) was detected in healthy brains, and its
      microRNA was also detected in glioblastoma patients' plasma. However, a direct
      link between KSHV infection and glioblastoma is currently not known. In this
      study, we infected glioblastoma cells and glioma stem-like cells (GSCs) with KSHV
      to establish an in vitro cell model for KSHV-infected glioblastoma cells and
      glioma stem-like cells in order to identify virologic outcomes that overlap with
      markers of aggressive disease. Latently KSHV-infected glioblastoma cells and GSCs
      were successfully established. Additionally, using these cell models, we found
      that KSHV infection modulates the proliferation of glioma stem-like cells.

PMID- 29032649
TI  - Production of Bacterial Quorum Sensing Antagonists, Caffeoyl- and Feruloyl-HSL,
      by an Artificial Biosynthetic Pathway.
AB  - A new series comprising phenylacetyl-homoserine lactones (HSLs), caffeoyl-HSL and
      feruloyl-HSL, was biologically synthesized using an artificial de novo
      biosynthetic pathway. We developed an Escherichia coli system containing
      artificial biosynthetic pathways that yield phenylacetyl-HSLs from simple carbon
      sources. These artificial biosynthetic pathways contained the LuxI-type synthase
      gene (rpaI) in addition to caffeoyl-CoA and feruloyl-CoA biosynthetic genes,
      respectively. Finally, the yields for caffeoyl-HSL and feruloyl-HSL were 97.1 +/-
      10.3 and 65.2 +/- 5.7 mg/l, respectively, by tyrosine-overproducing E. coli with
      a L-methionine feeding strategy. In a quorum sensing (QS) competition assay,
      feruloyl-HSL and p-coumaroyl-HSL antagonized the QS receptor TraR in
      Agrobacterium tumefaciens NT1, whereas caffeoyl-HSL did not.

PMID- 29032650
TI  - Immunomodulatory Potential of Weissella cibaria in Aged C57BL/6J Mice.
AB  - Aging is associated with distinct changes in immune cells and a decline in immune
      function, leading to increased susceptibility to infection and reduced responses
      to vaccination. Certain strains of lactic acid bacteria exert beneficial effects
      on the immune system. Previously, we reported that Weissella cibaria JW15
      isolated from kimchi possesses immune stimulatory activity in vitro. In the
      present study, we further investigated whether oral administration of JW15
      improves immune function in aged mice. Eighteen-month-old female mice were
      administered JW15 daily at low (JW15-L; 1 * 108 CFU/mouse) or high dosage (JW15
      H; 1 * 109 CFU/mouse), or with Lactobacillus rhamnosus GG (LGG) using oral
      gavage. Twomonth- old female mice were included as healthy young mice. After 4
      weeks, the mice were euthanized and immune profiles were analyzed using whole
      blood and spleen. In complete blood count analysis, the numbers of white and red
      blood cells were significantly increased in the JW15-L group compared with those
      in the old mouse (OM) control group. In addition, administration of either JW15
      of LGG resulted in higher numbers of splenocytes in comparison with the OM group.
      Furthermore, proliferative potentials were higher in all probiotic groups than
      OM. Cytokines such as IFN-gamma and IL-6 were secreted at higher levels in
      splenocytes isolated from JW15-fed mice than in OM control mice. Similarly, mRNA
      expression of various cytokines was altered in the JW15 groups. Collectively,
      these results suggest that JW15 supplementation induces immunomodulatory effects
      in aged mice and indicate JW15 as a potential probiotic strain to improve immune
      function in aged animals.

PMID- 29032651
TI  - Genomic Approaches for Understanding the Characteristics of Salmonella enterica
      subsp. enterica Serovar Typhimurium ST1120, Isolated from Swine Feces in Korea.
AB  - Salmonella enterica subsp. enterica serovar Typhimurium, one of the most common
      foodborne pathogens, is transmitted mainly through contaminated food derived from
      infected animals. In this study, S. Typhimurium ST1120, an isolate from pig feces
      in Korea, was subjected to whole-genome analysis to understand its genomic
      features associated with virulence. The genome of ST1120 was found to have a
      circular chromosome of 4,855,001 bp (GC content 52.2%) and a plasmid of 6,863 bp
      (GC content 46.0%). This chromosome was predicted to have 4,558 open reading
      frames (ORFs), 17 pseudogenes, 22 rRNA genes, and 86 tRNA genes. Its plasmid was
      predicted to have three ORFs. Comparative genome analysis revealed that ST1120
      was phylogenetically close to S. Typhimurium U288, a critical isolate in piggery
      farms and food chains in Europe. In silico functional analysis predicted that the
      ST1120 genome harbored multiple genes associated with virulence and stress
      resistance, including Salmonella pathogenicity islands (SPIs containing SPI-1 to
      SPI-5, SPI-13, and SPI-14), C63PI locus, ST104 prophage locus, and various
      antibiotic resistance genes. In accordance with these analysis results, ST1120
      showed competence in invasion and survival abilities when it was added to host
      cells. It also exhibited robust resistance against antibiotics in comparison with
      other S. Typhimurium strains. This is the first report of the complete genome
      sequence of S. Typhimurium isolated from swine in Korea. Comparative genome
      analysis between ST1120 and other Salmonella strains would provide fruitful
      information toward understanding Salmonella host specificity and developing
      control measures against S. Typhimurium infection.

PMID- 29032652
TI  - Molecular Characterization of Salmonella Genomic Island 1 in Proteus mirabilis
      Isolates from Chungcheong Province, Korea.
AB  - The emergence and dissemination of Salmonella genomic island 1 (SGI1) are
      strongly associated with the occurrence of multidrug-resistant (MDR)
      enterobacteria in humans and animals. Diverse SGI1s have been reported among
      Salmonella enterica and Proteus mirabilis in several countries. We aimed to
      characterize SGI1 in P. mirabilis isolates from humans and chickens in
      Chungcheong Province, Korea. A total of 44 P. mirabilis isolates were recovered
      from humans (n = 20) and chickens (n = 24). Antimicrobial susceptibility was
      determined by disk diffusion assay. To detect and characterize SGI1s, PCR
      amplification and PCR mapping experiments were performed. Repetitive extragenic
      palindromic-PCR (REP-PCR) was performed to assess the clonality of the isolates.
      The four P. mirabilis strains (16.7%) from chicken harbored a SGI1, whereas none
      of the isolates from clinical specimens contained SGI1. The SGI1s detected in our
      study were all confirmed as SGI1-PmABB harboring aminoglycoside-resistant genes
      (aacCA5 and aadA7). In P. mirabilis isolates, the presence of SGI1-PmABB was
      significantly correlated with high resistance rates of the isolates to
      antimicrobial agents, such as gentamicin, streptomycin, and spectinomycin.
      Moreover, the four SGI1-bearing isolates showed the same REP-PCR patterns and
      that suggested both horizontal and clonal spread of the isolates. This study is
      the first attempt to determine SGI1s in P. mirabilis isolates in Korea. We
      confirmed that P. mirabilis isolates carrying SGI1-PmABB were distributed at
      poultry farms in Korea. The present study emphasizes the need for continuous
      monitoring of SGI1s to prevent spreading of the MDR genomic islands among P.
      mirabilis isolates from humans and animals.

PMID- 29032653
TI  - Bacterial Hormone-Sensitive Lipases (bHSLs): Emerging Enzymes for
      Biotechnological Applications.
AB  - Lipases are important enzymes with biotechnological applications in dairy,
      detergent, food, fine chemicals, and pharmaceutical industries. Specifically,
      hormone-sensitive lipase (HSL) is an intracellular lipase that can be stimulated
      by several hormones, such as catecholamine, glucagon, and adrenocorticotropic
      hormone. Bacterial hormone-sensitive lipases (bHSLs), which are homologous to the
      C-terminal domain of HSL, have alpha/beta-hydrolase fold with a catalytic triad
      composed of His, Asp, and Ser. These bHSLs could be used for a wide variety of
      industrial applications because of their high activity, broad substrate
      specificity, and remarkable stability. In this review, the relationships among
      HSLs, the microbiological origins, the crystal structures, and the
      biotechnological properties of bHSLs are summarized.

PMID- 29032654
TI  - Tyndallized Lactobacillus plantarum HY7712 Restores Whole-Body gamma-Irradiation
      Impaired Th Cell Differentiation in Mice.
AB  - In the present study, we investigated the effect of tyndallized HY7712 (tHY7712)
      on the expression of Th cell specific transcription factors and cytokines in
      whole-body gamma-irradiated mice. Oral administration of tHY7712 strongly
      recovered the gamma-irradiation-suppressed expression of helper T (Th) cell- and
      regulatory T cell-related transcription factors and cytokines, such as T-bet,
      Foxp3, IFN-gamma, TNF-alpha, and IL-10, and suppressed Th2 cell-associated
      transcription factor and cytokine GATA3 and IL-5, respectively. Furthermore,
      compared with the control, tHY7712 treatment also restored gamma-irradiation
      impaired natural killer and cytotoxic T cell activities against YAC-1 tumor cells
      to 97.8% and 98.6%, respectively.

PMID- 29032656
TI  - Haemoproteus in barn and collared scops owls from Thailand.
AB  - The barn owl (BO) and the collared scops owl (CSO) are common nocturnal raptors
      throughout Thailand. Blood samples from 23 adult BOs and 14 CSOs were collected
      and processed for complete blood cell counts and parasite morphological
      examinations. Two Haemoproteus-positive samples were processed for
      ultrastructural observation. Polymerase chain reaction (PCR) analysis for a
      partial cytochrome b gene (cytb) from Haemoproteus was performed in all samples.
      Haemoproteus presence detected by light microscopy was lower than that detected
      by PCR (30.4% and 34.8%, respectively, in BO; and 50.0% and 78.6%, respectively,
      in CSO). Comparative hematology revealed that Haemoproteus-positive BOs had
      higher mean cell hemoglobin concentration, total leukocyte, absolute heterophil,
      basophil, and monocyte counts than Haemoproteus-negative BOs, but no significant
      differences between Haemoproteus-negative and -positive CSOs. Monocyte
      ultrastructure analysis revealed a role in the elimination of gametocytes.
      Morphologically, the Haemoproteus in 3 BOs and 6 CSOs were identified as H.
      noctuae, while that in 1 CSO was identified as H. syrnii. Phylogenetic analysis
      indicated the Haemoproteus spp. in 8 BOs and 7 CSOs were not closely related to
      H. noctuae or H. syrnii, and the cytb of 2 CSOs was that of H. syrnii. These
      results should be useful for study of Haemoproteus.

PMID- 29032655
TI  - Microglial involvement in the development of olfactory dysfunction.
AB  - Olfactory impairment is the most common clinical manifestation among the elderly,
      and its prevalence increases sharply with age. Notably, growing evidence has
      shown that olfactory dysfunction is the first sign of neurodegeneration,
      indicating the importance of olfactory assessment as an early marker in the
      diagnosis of neurological disorders. In this review, we describe the nature of
      olfactory dysfunction and the advantage of using animal models in olfaction
      study, and we include a brief introduction to olfactory behavior tests widely
      used in this field. The contribution of microglia in the neurodegenerative
      processes including olfactory impairment is then discussed to provide a
      comprehensive description of the physiopathological role of interactions between
      neurons and microglia within the olfactory system.

PMID- 29032657
TI  - Optimization of scan delay for multi-phase computed tomography by using bolus
      tracking in normal canine kidney.
AB  - This study was performed to optimize scan delays for canine kidney by using a
      bolus-tracking technique. In six beagle dogs, computed tomography (CT) of the
      kidney was performed three times in each dog with different scan delays after a
      bolus-tracking trigger of 100 Hounsfield units (HU) of aortic enhancement. Delays
      were 5, 20, 35, and 50 sec for the first scan, 10, 25, 40, and 55 sec for the
      second scan, and 15, 30, 45, and 60 sec for the third scan. The renal artery-to
      vein contrast difference peaked at 5 sec, and the renal cortex-to-medulla
      contrast difference peaked at 10 sec. The renal cortex-to-medulla contrast
      difference approached zero at a scan delay of 30 sec after the bolus trigger. For
      the injection protocol used in this study, the optimal scan delay times for renal
      arterial, corticomedullary, and nephrographic phases were 5, 10, and 30 sec after
      triggering at 100 HU of aortic enhancement using the bolus-tracking technique.
      The bolus-tracking technique is useful in multi-phase renal CT study as it
      compensates for different transit times to the kidney among different animals,
      requires a small dose of contrast media, and does not require additional patient
      radiation exposure.

PMID- 29032658
TI  - Analysis of protein expression in Brucella abortus mutants with different growth
      rates by two-dimensional gel electrophoresis and LC-MS/MS peptide analysis.
AB  - Brucella abortus is a bacterium that causes brucellosis and is the causative
      agent of worldwide zoonoses. Pathogenesis of the B. abortus infection is
      complicated, and several researchers have attempted to elucidate the infection
      mechanism of B. abortus. While several proteins have been revealed as pathogenic
      factors by previous researchers, the underlying mechanism of B. abortus infection
      is unresolved. In this study, we identified proteins showing different expression
      levels in B. abortus mutants with different biological characteristics that were
      generated by random insertion of a transposon. Five mutants were selected based
      on biological characteristics, in particular, their growth features. Total
      proteins of mutant and wild-type B. abortus were purified and subjected to two
      dimensional gel electrophoresis. Thirty protein spots of each mutant with
      expression increases or decreases were selected; those with a change of more than
      2-fold were compared with the wild-type. Selected spots underwent liquid
      chromatography tandem mass spectrometry for peptide analysis. DnaK and ClpB,
      involved in protein aggregation, increased. SecA and GAPDH, associated with
      energy metabolism, decreased in some mutants with a growth rate slower than that
      of the wild-type. Mutants with slower growth showed a decrease in energy
      metabolism-related proteins, while mutants with faster growth showed an increase
      in pathogenicity-related proteins.

PMID- 29032659
TI  - In silico analysis of putative drug and vaccine targets of the metabolic pathways
      of Actinobacillus pleuropneumoniae using a subtractive/comparative genomics
      approach.
AB  - Actinobacillus pleuropneumoniae is a Gram-negative bacterium that resides in the
      respiratory tract of pigs and causes porcine respiratory disease complex, which
      leads to significant losses in the pig industry worldwide. The incidence of drug
      resistance in this bacterium is increasing; thus, identifying new protein/gene
      targets for drug and vaccine development is critical. In this study, we used an
      in silico approach, utilizing several databases including the Kyoto Encyclopedia
      of Genes and Genomes (KEGG), the Database of Essential Genes (DEG), DrugBank, and
      Swiss-Prot to identify non-homologous essential genes and prioritize these
      proteins for their druggability. The results showed 20 metabolic pathways that
      were unique and contained 273 non-homologous proteins, of which 122 were
      essential. Of the 122 essential proteins, there were 95 cytoplasmic proteins and
      11 transmembrane proteins, which are potentially suitable for drug and vaccine
      targets, respectively. Among these, 25 had at least one hit in DrugBank, and
      three had similarity to metabolic proteins from Mycoplasma hyopneumoniae, another
      pathogen causing porcine respiratory disease complex; thus, they could serve as
      common therapeutic targets. In conclusion, we identified glyoxylate and
      dicarboxylate pathways as potential targets for antimicrobial therapy and tetra
      acyldisaccharide 4'-kinase and 3-deoxy-D-manno-octulosonic-acid transferase as
      vaccine candidates against A. pleuropneumoniae.

PMID- 29032662
TI  - White Bile in Malignant Biliary Obstruction: A Poor Prognostic Marker.

PMID- 29032660
TI  - Recombinant-attenuated Salmonella Pullorum strain expressing the hemagglutinin
      neuraminidase protein of Newcastle disease virus (NDV) protects chickens against
      NDV and Salmonella Pullorum challenge.
AB  - Newcastle disease virus (NDV) and Salmonella Pullorum have significant damaging
      effects on the poultry industry, but no previous vaccine can protect poultry
      effectively. In this study, a recombinant-attenuated S. Pullorum strain secreting
      the NDV hemagglutinin-neuraminidase (HN) protein, C79-13DeltacrpDeltaasd (pYA
      HN), was constructed by using the suicide plasmid pREasd-mediated bacteria
      homologous recombination method to form a new bivalent vaccine candidate against
      Newcastle disease (ND) and S. Pullorum disease (PD). The effect of this vaccine
      candidate was compared with those of the NDV LaSota and C79-13DeltacrpDeltaasd
      (pYA) strains. The serum hemagglutination inhibition antibody titers, serum
      immunoglobulin G (IgG) antibodies, secretory IgA, and stimulation index in
      lymphocyte proliferation were increased significantly more (p < 0.01) in chickens
      inoculated with C79-13DeltacrpDeltaasd (pYA-HN) than with C79-13DeltacrpDeltaasd
      (pYA) but were not significantly increased compared with the chickens immunized
      with the LaSota live vaccine (p > 0.05). Moreover, the novel strain provides 60%
      and 80% protective efficacy against the NDV virulent strain F48E9 and the S.
      Pullorum virulent strain C79-13. In summary, in this study, a recombinant
      attenuated S. Pullorum strain secreting NDV HN protein was constructed. The
      generation of the S. Pullorum C79-13DeltacrpDeltaasd (pYA-HN) strain provides a
      foundation for the development of an effective living-vector double vaccine
      against ND and PD.

PMID- 29032661
TI  - A Prospective Study of Eosinophilic Esophagitis and the Expression of Tight
      Junction Proteins in Patients with Gastroesophageal Reflux Disease Symptoms.
AB  - Background/Aims: Eosinophilic esophagitis (EoE) is often erroneously diagnosed as
      gastroesophageal reflux disease (GERD). The aim of this study is to investigate
      the prevalence of EoE and the expression of tight junction (TJ) proteins in
      patients with GERD symptoms. Methods: One hundred patients with GERD symptoms and
      10 healthy controls were prospectively studied. Sixty-two patients had symptoms
      refractory to proton pump inhibitors (PPI). All patients underwent esophageal
      biopsy. Patients were diagnosed with EoE if the number of eosinophil granulocytes
      per high-power field was >=15. Immunohistochemical analysis of TJ proteins
      (claudin-1, claudin-4, occludin, and zonula occludin-1 [ZO-1]) was performed.
      Results: EoE was diagnosed in six of 100 patients (6%) with GERD symptoms and in
      six patients (9.7%) of 62 patients with PPI-refractory GERD. Only one had typical
      EoE endoscopic findings. The proportion of ZO-1-positive cells was significantly
      lower in the lower than in the middle esophagus (56.0%+/-14.0% vs 66.0%+/-11.5%,
      p<0.05). There were no significant correlations between TJ protein expression and
      GERD symptoms. Conclusions: The prevalence of EoE among patients with PPI
      refractory GERD is approximately 10%. Regardless of endoscopic findings,
      esophageal biopsy is crucial in diagnosing EoE. The disruption of ZO-1 expression
      in the lower esophagus is significantly associated with GERD symptoms.

PMID- 29032663
TI  - Number of Metastatic Lymph Nodes and Ratio of Metastatic Lymph Nodes to Total
      Number of Retrieved Lymph Nodes Are Risk Factors for Recurrence in Patients With
      Clinically Node Negative Papillary Thyroid Carcinoma.
AB  - OBJECTIVES: The number of metastatic lymph nodes (LNs) and the ratio between the
      number of metastatic LNs and the total number of retrieved LNs (the LN ratio
      [LNR]) have been proposed as risk factors for recurrence of papillary thyroid
      carcinoma (PTC). However, the significance of the number of LNs and the LNR in
      patients with clinically node negative PTC has not been clearly determined. The
      purpose of this study is to evaluate their significance. METHODS: We
      retrospectively analyzed 382 patients with PTC who had undergone total
      thyroidectomy with prophylactic central neck dissection (CND) between January
      2000 and December 2010. We excluded patients with lobectomy, concurrent lateral
      compartment neck dissection, a follow-up period less than at least 2 years,
      number of harvested central LNs less than or equal to one, clinically positive
      LN, distant metastasis, recurrent cancer or other types of malignancy. The
      correlations between recurrence and various clinicopathologic characteristics
      including tumor size, extrathyroidal extension (ETE), stage, number of metastatic
      central LNs, and the LNR were investigated. RESULTS: After a mean follow-up
      period of 82.2+/-26.4 months, recurrence occurred in 14 patients (3.7%). Tumor
      size >=20 mm, maximal ETE, presence of central LN metastasis, number of
      metastatic LNs >=2, and LNR >=0.31 correlated with recurrence in the univariate
      analysis. However, tumor size >=20 mm, maximal ETE, number of metastatic LNs >=2,
      and LNR >=0.31 were significantly associated with recurrence in the multivariate
      analysis (hazard ratio=6.61, 7.17, 3.43, and 11.23, respectively). CONCLUSION:
      The LNR and the number of metastatic LNs are independent prognostic risk factors
      for recurrence in patients with clinically node negative PTC, and these factors
      can be used to guide postoperative adjuvant therapy and follow-up strategy after
      prophylactic CND.

PMID- 29032664
TI  - The Protective Effect of Egb 761 Against 3-Nitropropionic Acid-Induced Hearing
      Loss: The Role of Sirtuin 1.
AB  - OBJECTIVES: Local administration of 3-nitropropionic acid (3-NP) to the inner ear
      induces sensorineural hearing loss. Several studies have shown the otoprotective
      effects of ginkgo biloba extract EGb 761. Moreover, EGb 761 has been reported to
      activate Sirtuin 1 (SIRT1). The present study was designed to investigate whether
      EGb 761 prevents 3-NP-induced sensorineural hearing loss and determine its
      effects on the expression of SIRT1. METHODS: Sprague Dawley rats were divided
      into four experimental groups: control group receiving vehicle of 3-NP, EGb group
      receiving EGb 761, 3-NP group receiving 3-NP, and EGb+3-NP group receiving EGb
      761 and 3-NP. EGb 761 was given orally for 5 days. The 3-NP solution was injected
      into the tympanum 3 days after the start of EGb 761 administration. The auditory
      brainstem response was recorded before and after the injection. At 4 weeks after
      the administration of 3-NP or vehicle of 3-NP, cochleae were harvested, and
      hematoxylin and eosin staining and immunohistochemistry for SIRT1 antibody were
      performed. RESULTS: EGb+3-NP group showed significantly lower threshold shifts
      than 3-NP group. There was a significant preservation of type II fibrocytes and
      spiral ganglion cells in EGb+3-NP group than in 3-NP group. In EGb+3-NP group,
      there was a significantly greater number of SIRT1 immunopositive type II
      fibrocytes and spiral ganglion cells than in 3-NP group. Calculating the
      percentage of SIRT1 immunoreactive type II fibrocytes and spiral ganglion cells
      in viable type II fibrocytes and spiral ganglion cells, respectively, EGb+3-NP
      group showed significantly higher SIRT1 immunoreactive cells than 3-NP group.
      CONCLUSION: These results suggest that EGb 761 may prevent hearing loss induced
      by 3-NP in an acute ototoxic animal model, which appears to be related with SIRT1
      expression.

PMID- 29032665
TI  - Does standoff material affect acoustic radiation force impulse elastography? A
      preclinical study of a modified elastography phantom.
AB  - PURPOSE: This study was conducted to determine the influence of standoff material
      on acoustic radiation force impulse (ARFI) measurements in an elasticity phantom
      by using two different probes. METHODS: Using ARFI elastography, 10 observers
      measured the shear wave velocity (SWV, m/sec) in different lesions of an
      elasticity phantom with a convex 4C1 probe and a linear 9L4 probe. The
      experimental setup was expanded by the use of an interposed piece of porcine
      muscle as standoff material. The probe pressure on the phantom was registered.
      RESULTS: Faulty ARFI measurements occurred more often when quantifying the
      hardest lesion (74.0 kPa 4.97 m/sec) by the 9L4 probe with the porcine muscle as
      a standoff material interposed between the probe and the phantom. The success
      rate for ARFI measurements in these series was 52.4%, compared with 99.5% in the
      other series. The SWV values measured with the 9L4 probe were significantly
      higher (3.33+/-1.39 m/sec vs. 2.60+/-0.74 m/sec, P<0.001 in the group without
      muscle) and were closer to the reference value than those measured with the 4C1
      probe (0.25+/-0.23 m/sec vs. 0.85+/-1.21 m/sec, P<0.001 in the same group). The
      SWV values measured when using the muscle as a standoff material were lower than
      those without the muscle (significant for 9L4, P=0.040). The deviation from the
      reference value and the variance increased significantly with the 9L4 probe if
      the muscle was in situ (B=0.27, P=0.004 and B=0.32, P<0.001). In our study, the
      pressure exerted by the operator had no effect on the SWV values. CONCLUSION: The
      presence of porcine muscle acting as a standoff material influenced the
      occurrence of failed measurements as well as the variance and the accuracy of the
      measured values. The linear high-frequency probe was particularly affected.

PMID- 29032667
TI  - Synchronous parathyroid carcinoma and papillary thyroid carcinoma in a patient
      with long-standing schizophrenia.

PMID- 29032666
TI  - 24-Hour blood pressure response to lower dose (30 mg) fimasartan in Korean
      patients with mild to moderate essential hypertension.
AB  - BACKGROUND/AIMS: Fimasartan is an angiotensin type 1 receptor blocker (ARB) which
      has comparable efficacy and tolerability with other ARBs. The aim of this study
      was to evaluate 24-hour blood pressure (BP) lowering efficacy and the
      tolerability of the low dose fimasartan compared with valsartan in patients with
      mild to moderate hypertension. METHODS: This study was a phase II, prospective,
      multicenter, randomized, double-blind, parallel-grouped trial. A total of 75
      hypertensive patients, whose mean ambulatory BP monitoring values were >= 135/85
      mmHg, were randomized to either fimasartan 30 mg or valsartan 80 mg daily. The
      primary efficacy endpoint was the change in the mean 24-hour systolic BP (SBP)
      values from the baseline and at the week 8. Secondary endpoints included the
      change in the mean 24-hour diastolic BP values, the daytime and the nighttime
      mean BP values at week 8, the trough-to-peak (T/P) ratio and the smoothness
      index. RESULTS: At week 8, the mean 24-hour SBP values significantly decreased in
      both groups; -10.5 +/- 11.9 mmHg (p < 0.0001) in the fimasartan group and -5.5 +/
      11.6 mmHg (p = 0.0307) in the valsartan group. The difference between two groups
      was 4.3 +/- 2.9 mmHg but there was no statistical significance (p = 0.1392). The
      global T/P ratio in the fimasartan 30 mg groups were 0.48 and 0.40 in the
      valsartan 80 mg group, respectively (p = 0.3411). The most frequent adverse
      events (AEs) were acute pharyngitis and there were no cases of severe AEs.
      CONCLUSIONS: In mild-to-moderate hypertensive patients, low dose (30 mg)
      fimasartan showed comparable 24-hour BP lowering efficacy compared with valsartan
      (80 mg). There was no difference in tolerability between two groups.

PMID- 29032668
TI  - Multiple giant calcified aneurysms of three coronary arteries.

PMID- 29032669
TI  - Xp11.2 translocation renal cell carcinoma in the autosomal dominant polycystic
      kidney disease patient with preserved renal function.

PMID- 29032670
TI  - Kinetics and Products of the Reactions of Fluorine Atoms with ClNO and Br2 from
      295 to 950 K.
AB  - The kinetics and products of the reactions of F atoms with Br2 and ClNO have been
      studied in a flow reactor coupled with an electron impact ionization mass
      spectrometer at nearly 2 Torr total pressure of helium and over a wide
      temperature range, T = 295-950 K. The rate constant of the reaction F + ClNO ->
      products (1) was determined under pseudo-first order conditions, monitoring the
      kinetics of F atom consumption in excess of ClNO. The measured temperature
      independent rate constant, k1 = (1.29 +/- 0.13) * 10-10 cm3 molecule-1 s-1 (T =
      299-950 K), was found to be in excellent agreement with the only previous low
      temperature study which allowed to recommend the value of k1 in an extended
      temperature range, 228-950 K. FCl and Cl atoms were observed as the reactions
      products (corresponding to two reaction pathways: Cl-atom abstraction and
      replacement with fluorine atom, respectively) with the independent of
      temperature, in the range 295-948 K, yields of 0.68 +/- 0.10 and 0.32 +/- 0.05,
      respectively. Rate constant of the reaction F + Br2 (2), k2 = (1.28 +/- 0.20) *
      10-10 cm3 molecule-1 s-1, determined using both absolute and relative rate
      methods, was found to be independent of temperature at T = 299-940 K.

PMID- 29032671
TI  - Spectroelectrochemical Reverse Engineering DemonstratesThat Melanin's Redox and
      Radical Scavenging Activities Are Linked.
AB  - Melanins are ubiquitous in nature but their biological activities and functions
      have been difficult to discern. Conventional approaches to determine material
      function start by resolving structure and then characterize relevant properties.
      These approaches have been less successful for melanins because of their complex
      structure and insolubility, and because their relevant properties are not readily
      characterized by conventional methods. Here, we report a novel
      spectroelectrochemical reverse engineering approach that focuses on redox and
      radical scavenging activities. In this method, the melanin is immobilized in a
      permeable hydrogel film adjacent to an electrode and this immobilized melanin is
      probed using diffusible mediators and complex electrical inputs. Response
      characteristics are measured using two modalities, electrochemical currents
      associated with the reaction of diffusible mediators, and optical absorbance
      associated with the presence of diffusible free radicals. Using this method, we
      observed that both Sepia and fungal melanins are redox active and can repeatedly
      exchange electrons to be switched between oxidized and reduced states. Further,
      we observed that these melanins can quench radicals either by donating or
      accepting electrons. Finally, we demonstrate that the melanins' radical
      scavenging activities are dependent on their redox state such that a melanin must
      be reduced to have donatable electrons to quench oxidative free radicals, or must
      be oxidized to accept electrons from reductive free radicals. While the
      observation that melanin is redox-active is consistent with their well-accepted
      beneficial (radical-scavenging) and detrimental (pro-oxidant) activities, these
      observations may also support less well-accepted proposed functions for melanin
      in energy harvesting and redox communication.

PMID- 29032672
TI  - Energy Level Engineering of MoS2 by Transition-Metal Doping for Accelerating
      Hydrogen Evolution Reaction.
AB  - Water-splitting devices for hydrogen generation through electrolysis (hydrogen
      evolution reaction, HER) hold great promise for clean energy. However, their
      practical application relies on the development of inexpensive and efficient
      catalysts to replace precious platinum catalysts. We previously reported that HER
      can be largely enhanced through finely tuning the energy level of molybdenum
      sulfide (MoS2) by hot electron injection from plasmonic gold nanoparticles. Under
      this inspiration, herein, we propose a strategy to improve the HER performance of
      MoS2 by engineering its energy level via direct transition-metal doping. We find
      that zinc-doped MoS2 (Zn-MoS2) exhibits superior electrochemical activity toward
      HER as evidenced by the positively shifted onset potential to -0.13 V vs RHE. A
      turnover of 15.44 s-1 at 300 mV overpotential is achieved, which by far exceeds
      the activity of MoS2 catalysts reported. The large enhancement can be attributed
      to the synergistic effect of electronic effect (energy level matching) and
      morphological effect (rich active sites) via thermodynamic and kinetic
      acceleration, respectively. This design opens up further opportunities for
      improving electrocatalysts by incorporating promoters, which broadens the
      understanding toward the optimization of electrocatalytic activity of these
      unique materials.

PMID- 29032673
TI  - Effects of Sulfide Concentration and Dissolved Organic Matter Characteristics on
      the Structure of Nanocolloidal Metacinnabar.
AB  - Understanding the speciation of divalent mercury (Hg(II)) in aquatic systems
      containing dissolved organic matter (DOM) and sulfide is necessary to predict the
      conversion of Hg(II) to bioavailable methylmercury. We used X-ray absorption
      spectroscopy to characterize the structural order of mercury in Hg(II)-DOM
      sulfide systems for a range of sulfide concentration (1-100 MUM), DOM aromaticity
      (specific ultraviolet absorbance (SUVA254)), and Hg(II)-DOM and Hg(II)-DOM
      sulfide equilibration times (4-142 h). In all systems, Hg(II) was present as
      structurally disordered nanocolloidal metacinnabar (beta-HgS). beta-HgS
      nanocolloids were significantly smaller or less ordered at lower sulfide
      concentration, as indicated by under-coordination of Hg(II) in beta-HgS. The size
      or structural order of beta-HgS nanocolloids increased with increasing sulfide
      abundance and decreased with increasing SUVA254 of the DOM. The Hg(II)-DOM or
      Hg(II)-DOM-sulfide equilibration times did not significantly influence the extent
      of structural order in nanocolloidal beta-HgS. Geochemical factors that control
      the structural order of nanocolloidal beta-HgS, which are expected to influence
      nanocolloid surface reactivity and solubility, should be considered in the
      context of mercury bioavailability.

PMID- 29032674
TI  - Doxorubicin-Loaded Unimolecular Micelle-Stabilized Gold Nanoparticles as a
      Theranostic Nanoplatform for Tumor-Targeted Chemotherapy and Computed Tomography
      Imaging.
AB  - Current research is mainly trending toward addressing the development of
      multifunctional nanocarriers that could precisely reach disease sites, release
      drugs in a controlled-manner, and act as an imaging agent for both diagnosis and
      targeted therapy. In this study, a pH-sensitive theranostic nanoplatform as a
      promising dual-functional nanovector for tumor therapy and computed tomography
      (CT) imaging was developed. The 21-arm star-like triblock polymer of beta
      cyclodextrin-{poly(epsilon-caprolactone)-poly(2-aminoethyl methacrylate)
      poly[poly(ethylene glycol) methyl ether methacrylate]}21 [beta-CD-(PCL-PAEMA
      PPEGMA)21] with stable unimolecular micelles formed in aqueous solution was first
      synthesized by combined ROP with ARGET ATRP techniques and then was used as a
      template for fabricating gold nanoparticles (AuNPs) with uniform sizes and
      excellent colloidal stability in situ followed by the encapsulation of
      doxorubicin (DOX) with maximum entrapment efficiency up to 60% to generate the
      final product beta-CD-(PCL-PAEMA-PPEGMA)21/AuNPs/DOX. Furthermore, dissipative
      particle dynamics (DPD) simulations revealed further details of the formation
      process of unimolecular micelles and the morphologies and distributions of AuNPs
      and DOX. Almost 80% of DOX was released in 120 h in an acidic tumoral environment
      in an in vitro drug release experiment, and the experiments both in vitro and in
      vivo demonstrated the fact that beta-CD-(PCL-PAEMA-PPEGMA)21/AuNPs/DOX exhibited
      similar antitumor efficacy to free DOX and effective CT imaging performance.
      Therefore, we believe this structurally stable unimolecular micelle-based
      nanoplatform synergistically integrated with anticancer drug delivery and CT
      imaging capabilities hold great promise for future cancer theranostics.

PMID- 29032675
TI  - Carbon, Hydrogen, and Nitrogen Isotope Fractionation Trends in N
      Nitrosodimethylamine Reflect the Formation Pathway during Chloramination of
      Tertiary Amines.
AB  - Assessing the precursors and reactions leading to the carcinogenic N
      nitrosodimethylamine (NDMA) during drinking water disinfection is a major
      challenge. Here, we investigate whether changes of 13C/12C, 2H/1H, and 15N/14N
      ratios of NDMA give rise to isotope fractionation trends that can be used to
      infer NDMA formation pathways. We carried out compound-specific isotope analysis
      (CSIA) of NDMA during chloramination of four tertiary amines that produce NDMA at
      high yields, namely ranitidine, 5-(dimethylaminomethyl)furfuryl alcohol, N,N
      dimethylthiophene-2-methylamine, and N,N-dimethylbenzylamine. Carbon and hydrogen
      isotope ratios of NDMA function as fingerprints of the N(CH3)2 moiety and exhibit
      only minor isotope fractionation during the disinfection process. Nitrogen
      isotope ratios showed that NH2Cl is the source of the N atom of the nitroso
      group. The large enrichment of 15N in NDMA was indicative of the isotope effects
      pertinent to bond-cleavage and bond-formation reactions during chloramination of
      the tertiary amines. Correlation of delta15N versus delta13C values of NDMA
      resulted in trend lines that were not affected by the type of tertiary amine and
      treatment conditions, suggesting that the observed C and N isotope fractionation
      in NDMA may be diagnostic for NDMA precursors and formation pathways during
      chloramination.

PMID- 29032677
TI  - Ultrasensitive Ratiometric Homogeneous Electrochemical MicroRNA Biosensing via
      Target-Triggered Ru(III) Release and Redox Recycling.
AB  - A new label-free and enzyme-free ratiometric homogeneous electrochemical microRNA
      biosensing platform was constructed via target-triggered Ru(III) release and
      redox recycling. To design the effective ratiometric dual-signal strategy,
      [Ru(NH3)6]3+ (Ru(III)), as one of the electroactive probes, was ingeniously
      entrapped in the pores of the positively charged mesoporous silica nanoparticle
      (PMSN), and another electroactive probe, [Fe(CN)6]3- (Fe(III)), was selected to
      facilitate Ru(III) redox recycling due to its distinctly separated reduction
      potential and different redox properties. Owing to the liberation of the formed
      RNA-ssDNA complex from PMSN, the target miRNA triggered the Ru(III) release and
      was quickly electroreduced to Ru(II), and then, the in-site-generated Ru(II)
      could be chemically oxidized back to Ru(III) by Fe(III). Thus, with the release
      of Ru(III) and the consumption of Fe(III), a significant enhancement for the
      ratio of electroreduction current [Ru(NH3)6]3+ over [Fe(CN)6]3-
      (IRu(III)/IFe(III)) value was observed, which was dependent on the concentration
      of the target miRNA. Consequently, a simple, accurate, and ultrasensitive method
      for the miRNA assay was readily realized. Furthermore, the limit of detection
      (LOD) of our method was down to 33 aM (S/N = 3), comparable or even superior to
      other approaches reported in literature. More importantly, it also exhibited
      excellent analytical performance in the complex biological matrix cell lysates.
      Therefore, this homogeneous biosensing strategy not only provides an ingenious
      idea for realizing simple, rapid, reliable, and ultrasensitive bioassays but also
      has a great potential to be adopted as a powerful tool for precision medicine.

PMID- 29032676
TI  - Following the Molecular Mechanism of Decarbonylation of Unsaturated Cyclic
      Ketones Using Bonding Evolution Theory Coupled with NCI Analysis.
AB  - The synergetic use of bonding evolution theory (BET) and noncovalent interaction
      (NCI) analysis allows to obtain new insight into the bond breaking/forming
      processes and electron redistribution along the reaction path to understand the
      molecular mechanism of a reaction and recognize regions of strong and weak
      electron pairing. This viewpoint has been considered for cheletropic extrusion of
      CO from unsaturated cyclic ketones cyclohepta-3,5-dien-1-one CHD, cyclopent-3-en
      1-one CPE, and bicyclo[2.2.1]hept-2-en-7-one BCH by using hybrid functional
      MPWB1K in conjugation with aug-cc-pVTZ basis set. Decarbonylation of CHD, CPE,
      and BCH are nonpolar cyclo-elimination reactions that are characterized by the
      sequence of turning points (TPs) as CHD, 1-11-C[CC]C?C?FFFTSC?C?C?-0:HT + CO;
      CPE, 1-8-CC[C?C?F?][FF][FF]FTS[C?C?]-0:BD + CO; and BCH, 1-8
      CC[C?C?]F[FF]FTS[C?C?]-0:CD + CO. Breaking of C-C bond between the terminal
      carbon atoms of diene/triene framework and carbon atom of CO fragment starts at a
      distance of ca. 1.9-2.0 A in the vicinity of the transition structure where the
      transition states are not reached yet. NCI analysis explains that the noncovalent
      interactions between two fragments appeared after the breaking of C-C bonds.

PMID- 29032678
TI  - Marangoni Effect-Driven Motion of Miniature Robots and Generation of Electricity
      on Water.
AB  - The well-known Marangoni effect perfectly supports the dynamic mechanism of
      organic solvent-swollen gels on water. On this basis, we report a series of
      energy conversion processes of concentrated droplets of polyvinylidene
      fluoride/dimethyl formamide (PVDF/DMF) that can transfer chemical-free energy to
      kinetic energy to rapidly rotate itself on water. This droplet (22.2 mg) is
      capable to offer kinetic energy of 0.099 MUJ to propel an artificial paper rocket
      of 31.8 mg to move over 560 cm on water at an initial velocity of 7.9 cm s-1. As
      the droplet increases to 35.0 mg, a paper goldfish of 10.6 mg can be driven to
      swim longer at a higher initial velocity of 20 cm s-1. The kinetic energy of the
      droplet can be further converted to electrical energy through an electromagnetic
      generator, in which as a 0.5 MOmega resistor is loaded, the peak output reaches
      6.5 mV that corresponds to the power density of 0.293 MUW kg-1. We believe that
      this report would open up a promising avenue to exploit energies for applications
      in miniature robotics.

PMID- 29032680
TI  - Accelerating Gold Nanorod Synthesis with Nanomolar Concentrations of
      Poly(vinylpyrrolidone).
AB  - A novel modification for the seedless synthesis of gold nanorods (AuNRs) has been
      developed. Nanomolar concentrations of 10 kDa poly(vinylpyrrolidone) (PVP) can be
      introduced to a growth solution containing 25, 50, or 100 mM
      cetyltrimethylammonium bromide (CTAB) to significantly reduce the dimensions of
      AuNRs. We found that PVP accelerates the growth rate of AuNRs by more than two
      times that of nanorods grown in 50 and 100 mM CTAB solutions. Additionally, there
      is a time-dependent effect of adding PVP to the nanorod growth solution that can
      be utilized to tune their aspect ratio. Because the concentration of PVP is far
      below the concentration of HAuCl4 in the reaction mixture, PVP primarily
      functions not as a reducing agent, but as a capping or templating ligand to
      stabilize the growing nanorods. Our reproducible protocol enables the synthesis
      of AuNRs in high yield with tunable sizes: 45 * 6.7, 28 * 5.5, and 12 * 4.5 nm
      for 100, 50, and 25 mM CTAB, respectively. We estimated the number of PVP chains
      per nanorod in growth solutions to be around 30, which suggests that the effect
      on the aspect ratio is caused by a direct interaction between the AuNR surface
      and the PVP.

PMID- 29032679
TI  - Mapping Free-Carriers in Multijunction Silicon Nanowires Using Infrared Near
      Field Optical Microscopy.
AB  - We report the use of infrared (IR) scattering-type scanning near-field optical
      microscopy (s-SNOM) as a nondestructive method to map free-carriers in axially
      modulation-doped silicon nanowires (SiNWs) with nanoscale spatial resolution.
      Using this technique, we can detect local changes in the electrically active
      doping concentration based on the infrared free-carrier response in SiNWs grown
      using the vapor-liquid-solid (VLS) method. We demonstrate that IR s-SNOM is
      sensitive to both p-type and n-type free-carriers for carrier densities above ~1
      * 1019 cm-3. We also resolve subtle changes in local conductivity properties,
      which can be correlated with growth conditions and surface effects. The use of s
      SNOM is especially valuable in low mobility materials such as boron-doped p-type
      SiNWs, where optimization of growth has been difficult to achieve due to the lack
      of information on dopant distribution and junction properties. s-SNOM can be
      widely employed for the nondestructive characterization of nanostructured
      material synthesis and local electronic properties without the need for contacts
      or inert atmosphere.

PMID- 29032681
TI  - Excited-State Proton Transfer on the Surface of a Therapeutic Protein, Protamine.
AB  - Proton transfer reactions on biosurfaces play an important role in a myriad of
      biological processes. Herein, the excited-state proton transfer reaction of 8
      hydroxypyrene-1,3,6-trisulfonate (HPTS) has been investigated in the presence of
      an important therapeutic protein, Protamine (PrS), using ground-state absorption,
      steady-state, and detailed time-resolved emission measurements. HPTS forms a 1:1
      complex with Protamine with a high association constant of 2.6 * 104 M-1. The
      binding of HPTS with Protamine leads to a significant modulation in the ground
      state prototropic equilibrium causing a downward shift of 1.1 unit in the acidity
      constant (pKa). In contrast to a large number of reports of slow proton transfer
      of HPTS on biosurfaces, interestingly, HPTS registers a faster proton transfer
      event in the presence of Protamine as compared to that of even the bulk aqueous
      buffer medium. Furthermore, the dimensionality of the proton diffusion process is
      also significantly reduced on the surface of Protamine that is in contrast to the
      behavior of HPTS in the bulk aqueous buffer medium, where the proton diffusion
      process is three-dimensional. The effect of ionic strength on the binding of HPTS
      toward PrS suggests a predominant role of electrostatic interaction between
      anionic HPTS and cationic Protamine, which is further supported by molecular
      docking simulations which predict that the most preferable binding site for HPTS
      on the surface of Protamine is surrounded by multiple cationic arginine residues.

PMID- 29032682
TI  - Improving the Stability and Size Tunability of Cesium Lead Halide Perovskite
      Nanocrystals Using Trioctylphosphine Oxide as the Capping Ligand.
AB  - Recently, all-inorganic cesium lead halide (CsPbX3, X = Cl, Br, and I)
      nanocrystals (NCs) have drawn wide attention because of their excellent
      optoelectronic properties and potential applications. However, one of the most
      significant challenges of such NCs is their low stability against protonic
      solvents. In this work, we demonstrate that by incorporating a highly branched
      capping ligand, trioctylphosphine oxide (TOPO), into the traditional oleic
      acid/oleylamine system, monodisperse CsPbX3 NCs with excellent optoelectronic
      properties can be achieved at elevated temperatures (up to 260  degrees C). The
      size of such NCs can be varied in a relatively wide range. The capping of TOPO on
      NCs has been verified through Fourier transform infrared spectroscopy
      measurement. More importantly, the presence of TOPO can dramatically improve the
      stability of CsPbX3 NCs against ethanol treatment. After ethanol treatment for
      100 min, the emission intensity of the TOPO-capped sample dropped only 5%,
      whereas that of non-TOPO-capped NCs dropped up to 86%. This work may shed some
      light on the preparation and application of CsPbX3 NCs with higher stability.

PMID- 29032683
TI  - Retrieving the Quantitative Chemical Information at Nanoscale from Scanning
      Electron Microscope Energy Dispersive X-ray Measurements by Machine Learning.
AB  - The quantitative composition of metal alloy nanowires on InSb semiconductor
      surface and gold nanostructures on germanium surface is determined by blind
      source separation (BSS) machine learning method using non-negative matrix
      factorization from energy dispersive X-ray spectroscopy (EDX) spectrum image maps
      measured in a scanning electron microscope (SEM). The BSS method blindly
      decomposes the collected EDX spectrum image into three source components, which
      correspond directly to the X-ray signals coming from the supported metal
      nanostructures, bulk semiconductor signal, and carbon background. The recovered
      quantitative composition is validated by detailed Monte Carlo simulations and is
      confirmed by separate cross-sectional transmission electron microscopy EDX
      measurements of the nanostructures. This shows that simple and achievable SEM EDX
      measurements together with machine learning non-negative matrix factorization
      based blind source separation processing could be successfully used for the
      nanostructures quantitative chemical composition determination. Our finding can
      make the chemical quantification at the nanoscale much faster and cost efficient
      for many systems.

PMID- 29032684
TI  - Effect of Boron on Thymic Cytokine Expression, Hormone Secretion, Antioxidant
      Functions, Cell Proliferation, and Apoptosis Potential via the Extracellular
      Signal-Regulated Kinases 1 and 2 Signaling Pathway.
AB  - Boron is an essential trace element in animals. Appropriate boron supplementation
      can promote thymus development; however, a high dose of boron can lead to adverse
      effects and cause toxicity. The influencing mechanism of boron on the animal body
      remains unclear. In this study, we examined the effect of boron on cytokine
      expression, thymosin and thymopoietin secretion, antioxidant function, cell
      proliferation and apoptosis, and extracellular signal-regulated kinases 1 and 2
      (ERK1/2) pathway in the thymus of rats. We found that supplementation with 10 and
      20 mg/L boron to the drinking water significantly elevated levels of interleukin
      2 (IL-2), interferon gamma (IFN-gamma), interleukin 4 (IL-4), and thymosin alpha1
      in the thymus of rats (p < 0.05), increased the number of positive proliferating
      cell nuclear antigen (PCNA+) cells and concentrations of glutathione peroxidase
      (GSH-Px) and phosphorylated extracellular signal-regulated kinase (p-ERK) (p <
      0.05), and promoted mRNA expression of PCNA and ERK1/2 in thymocytes (p < 0.05).
      However, the number of caspase-3+ cells and the expression level of caspase-3
      mRNA were reduced (p < 0.05). Supplementation with 40, 80, and 160 mg/L boron had
      no apparent effect on many of the above indicators. In contrast, supplementation
      with 480 and 640 mg/L boron had the opposite effect on the above indicators in
      rats and elevated levels of pro-inflammatory cytokines, such as interleukin 6 (IL
      6), interleukin 1beta (IL-1beta), and tumor necrosis factor alpha (TNF-alpha) (p
      < 0.05). Our study showed that supplementation of various doses of boron to the
      drinking water had a U-shaped dose-effect relationship with thymic cytokine
      expression, hormone secretion, antioxidant function, cell proliferation, and
      apoptosis. Specifically, supplementation with 10 and 20 mg/L boron promoted
      thymocyte proliferation and enhanced thymic functions. However, supplementation
      with 480 and 640 mg/L boron inhibited thymic functions and increased the number
      of apoptotic thymocytes, suggesting that the effects of boron on thymic functions
      may be caused via the ERK1/2 signaling pathway.

PMID- 29032685
TI  - Temperature-Dependent Implicit-Solvent Model of Polyethylene Glycol in Aqueous
      Solution.
AB  - A temperature (T)-dependent coarse-grained (CG) Hamiltonian of polyethylene
      glycol/oxide (PEG/PEO) in aqueous solution is reported to be used in implicit
      solvent material models in a wide temperature (i.e., solvent quality) range. The
      T-dependent nonbonded CG interactions are derived from a combined "bottom-up" and
      "top-down" approach. The pair potentials calculated from atomistic replica
      exchange molecular dynamics simulations in combination with the iterative
      Boltzmann inversion are postrefined by benchmarking to experimental data of the
      radius of gyration. For better handling and a fully continuous transferability in
      T-space, the pair potentials are conveniently truncated and mapped to an analytic
      formula with three structural parameters expressed as explicit continuous
      functions of T. It is then demonstrated that this model without further
      adjustments successfully reproduces other experimentally known key thermodynamic
      properties of semidilute PEG solutions such as the full equation of state (i.e.,
      T-dependent osmotic pressure) for various chain lengths as well as their cloud
      point (or collapse) temperature.

PMID- 29032687
TI  - On the Problem of Determining Aggregation Numbers from Surface Tension
      Measurements.
AB  - In view of the recent discovery of variable aggregation numbers in the vicinity
      of the critical micelle concentration (CMC), the mass-action-law theory of the
      surface tension isotherm of a micellar solution with variable aggregation numbers
      is formulated both for nonionic and ionic surfactants. It is shown that the shape
      of the surface tension isotherm should be concave in the logarithmic scale above
      the CMC. Considering a change in the isotherm slope at the CMC apparent break
      point, the problems of determining the aggregation number for nonionic micelles
      and the degree of counterion binding for ionic micelles are discussed. In case of
      the aggregation number variability near the CMC, finding the aggregation number
      above the CMC apparent break point is considered and a computational scheme is
      elaborated, requiring a higher precision for experiment. Some experimental data
      from the literature are analyzed, and the method of estimating the degree of
      counterion binding is improved.

PMID- 29032686
TI  - 3'-Hydroxypterostilbene Suppresses Colitis-Associated Tumorigenesis by Inhibition
      of IL-6/STAT3 Signaling in Mice.
AB  - 3'-Hydroxypterostilbene (trans-3,5-dimethoxy-3',4'-hydroxystilbene) presents in
      Sphaerophysa salsula, Pterocarpus marsupium, and honey bee propolis and has been
      reported to exhibit several biological activities. Herein, we aimed to explore
      the chemopreventive effects of dietary 3'-hydroxypterostilbene and underlying
      molecular mechanisms on colitis-associated cancer using the azoxymethane
      (AOM)/dextran sodium sulfate (DSS) model. 3'-Hydroxypterostilbene administration
      effectively ameliorated the colon shortening and number of tumors in AOM/DSS
      treated mice (3.2 +/- 1.2 of the high-dose treatment versus 13.8 +/- 5.3 of the
      AOM/DSS group, p < 0.05). Molecular analysis exhibited the anti-inflammatory
      activity of 3'-hydroxypterostilbene by a significant decrease in the levels of
      inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-6 (IL-6) (p <
      0.05). Moreover, dietary 3'-hydroxypterostilbene also significantly diminished IL
      6/signal transducer and activator of transcription signaling and restored colonic
      suppressor of cytokine signaling 3 levels in the colonic tissue of mice (p <
      0.05). Collectively, these results demonstrated for the first time the in vivo
      chemopreventive efficacy and molecular mechanisms of dietary 3'
      hydroxypterostilbene against colitis-associated colonic tumorigenesis.

PMID- 29032688
TI  - pH Dependence of the Aqueous Photochemistry of alpha-Keto Acids.
AB  - alpha-Keto acids are important, atmospherically relevant species, and their
      photochemistry has been considered in the formation and processing of aerosols.
      Despite their atmospheric relevance, the photochemistry of these species has
      primarily been studied under extremely low pH conditions. Using a variety of
      analytical techniques, we characterize the extent of hydration and deprotonation
      for solutions of two alpha-keto acids, pyruvic acid and 2-oxooctanoic acid, as a
      function of pH. We find that changes in the initial solution composition govern
      the accessibility of different photochemical pathways, resulting in slowed
      photolysis under high pH conditions and a shift in photoproducts that can be
      predicted mechanistically.

PMID- 29032689
TI  - Characterization and Degradation of Pectic Polysaccharides in Cocoa Pulp.
AB  - Microbial fermentation of the viscous pulp surrounding cocoa beans is a crucial
      step in chocolate production. During this process, the pulp is degraded, after
      which the beans are dried and shipped to factories for further processing.
      Despite its central role in chocolate production, pulp degradation, which is
      assumed to be a result of pectin breakdown, has not been thoroughly investigated.
      Therefore, this study provides a comprehensive physicochemical analysis of cocoa
      pulp, focusing on pectic polysaccharides, and the factors influencing its
      degradation. Detailed analysis reveals that pectin in cocoa pulp largely consists
      of weakly bound substances, and that both temperature and enzyme activity play a
      role in its degradation. Furthermore, this study shows that pulp degradation by
      an indigenous yeast fully relies on the presence of a single gene (PGU1),
      encoding for an endopolygalacturonase. Apart from their basic scientific value,
      these new insights could propel the selection of microbial starter cultures for
      more efficient pulp degradation.

PMID- 29032691
TI  - Conjugated hyperbilirubinemia after surgery. A diagnosis of Dubin-Johnson
      syndrome confirmed by genetic testing.
AB  - Dubin-Johnson syndrome is a rare benign inherited disorder, caused by mutations
      in ABCC2 gen, and it is characterized by predominantly conjugated
      hyperbilirubinemia that can be increased by intercurrent infectious illnesses or
      surgical procedures. We report the case of a 10 year-old patient who showed,
      after a surgical procedure for peritonitis due to appendicitis, jaundice and
      predominantly conjugated hyperbilirubinemia, and he was diagnosed with Dubin
      Johnson syndrome by genetic testing.

PMID- 29032692
TI  - A post-endoscopic retrograde cholangiopancreatography subcapsular hepatic
      hematoma.
AB  - Nowadays endoscopic retrograde cholangiopancreatography (ERCP) is a minimally
      invasive technique with a complication rate around 2.5% in expert hands, being
      the most frequent: acute pancreatitis, cholangitis, hemorrhage and perforation.
      An exceptional complication is subcapsular hepatic hematoma, first published in
      the literature in 2000, with few cases reported. Regarding the case published by
      Del Moral Martinez et al (Hepatic Hematoma after ERCP: presentation of two new
      cases. Rev Esp Enferm Dig 2017, Vol. 109, No. 6, pp. 470-473) we would like to
      contribute a reflection based on a recent clinical case in our center.

PMID- 29032693
TI  - From utopia to reality: increased survival in peritoneal carcinomatosis treated
      with cytoreduction and hyperthermic intraperitoneal chemotherapy.
AB  - We have read with great interest the article by Illan et al.1 entitled "Long
      survival in a patient with metastatic colorectal carcinoma: reality or utopia?"
      This article describes the case of a 42 year old patient with mucinous-type colon
      adenocarcinoma who had tumor recurrence with peritoneal metastases 18 months
      after resection of the primary tumor and adjuvant chemotherapy. After multiple
      metastasectomies and several lines of chemotherapy, the patient died 27 months
      after the recurrence.

PMID- 29032694
TI  - Short-term outcome of patients with colon cancer diagnosed by symptoms and
      screening.
AB  - Colon cancer diagnosed as part of a screening program, showed better short-term
      outcomes following surgery. These advantages seem to have impact on long-term
      outcomes as well.

PMID- 29032695
TI  - Hepatic veno-occlusive disease induced by Chinese medicinal herbs.
AB  - The potential hepatotoxic effects of products containing medicinal herbs, which
      are increasingly used without adequate control by health authorities, is well
      known. We report a case of toxic hepatic veno-occlusive disease (HVOD) presumably
      associated with the use of such herbal remedies.

PMID- 29032697
TI  - The Association of Sitting Time With Sarcopenia Status and Physical Performance
      at Baseline and 18-Month Follow-Up in the Residential Aged Care Setting.
AB  - This study investigated the association of sitting time with sarcopenia and
      physical performance in residential aged care residents at baseline and 18-month
      follow-up. Measures included the International Physical Activity Questionnaire
      (sitting time), European Working Group definition of sarcopenia, and the short
      physical performance battery (physical performance). Logistic regression and
      linear regression analyses were used to investigate associations. For each hour
      of sitting, the unadjusted odds ratio of sarcopenia was 1.16 (95% confidence
      interval [0.98, 1.37]). Linear regression showed that each hour of sitting was
      significantly associated with a 0.2-unit lower score for performance.
      Associations of baseline sitting with follow-up sarcopenia status and performance
      were nonsignificant. Cross-sectionally, increased sitting time in residential
      aged care may be detrimentally associated with sarcopenia and physical
      performance. Based on current reablement models of care, future studies should
      investigate if reducing sedentary time improves performance among adults in end
      of life care.

PMID- 29032696
TI  - Impact of improving postprandial glycemic control with intensifying insulin
      therapy in type 2 diabetes.
AB  - Worldwide, many people with type 2 diabetes are not at recommended glycemic
      targets and remain at increased risk of microvascular and macrovascular
      complications. Reaching recommended glycemic targets requires normalizing both
      fasting and postprandial glucose (PPG). For some patients, this will require
      addition of a prandial insulin delivered by injection to control PPG excursions.
      Evidence from epidemiological studies suggests an association between
      postprandial hyperglycemia and cardiovascular disease, and thus, expert
      guidelines recommend that treatment for elevated PPG not be delayed. Indeed,
      studies have demonstrated that PPG makes the greatest contribution to HbA1c in
      patients who are approaching, but have not yet reached HbA1c <7.0%. Appropriately
      timed exposure of the liver to insulin is critical in suppressing hepatic glucose
      output (and therefore PPG levels) after a meal. Rapid-acting insulin analogs,
      with their faster onset and shorter duration of action, offer advantages over
      regular human insulin. Unfortunately, even with improved
      pharmacokinetic/pharmacodynamic characteristics, rapid-acting insulin analogs are
      still unable to fully reproduce the rapid release of insulin into the portal
      circulation and suppression of hepatic glucose output that occurs in the
      individual without diabetes after starting a meal. The next generation of rapid
      acting insulin analogs will have an even more favorable pharmacokinetic profile
      that should allow patients to further improve glycemic control. Continuous
      subcutaneous insulin infusion (CSII) represents another option for intensifying
      therapy and improving postprandial control in some patients, and studies have
      shown that the benefits are sustainable long-term. However, it is currently
      unclear which patients stand to benefit the most from the extra expense and
      complexity of a CSII regimen, and further studies are needed.

PMID- 29032698
TI  - Text Messages Promoting Mental Imagery Increase Self-Reported Physical Activity
      in Older Adults: A Randomized Controlled Study.
AB  - OBJECTIVE: This study tested whether text messages prompting adults 50 years of
      age and older to perform mental imagery would increase aerobic physical activity
      (APA) duration using a randomized parallel trial design. METHOD: Participants
      were assigned to an Imagery 1, Imagery 2, or placebo group. For 4 weeks, each
      group was exposed to two conditions (morning text message vs. no morning text
      message). In the morning message condition, the imagery groups received a text
      message with the instruction to mentally imagine performing an APA, and the
      placebo group received a placebo message. All participants received an evening
      text message of "Did you do your cardio today? If yes, what did you do?" for 3
      days per week. RESULTS: Participants of the imagery groups reported significantly
      more weekly minutes of APA in the morning text message condition compared with
      the no morning message condition. CONCLUSION: Electronic messages were effective
      at increasing minutes of APA.

PMID- 29032699
TI  - A patient with aphasia using the nonsemantic lexical route for Kanji reading.
AB  - We report a patient with aphasia, caused by cerebral hemorrhage, who probably
      used the nonsemantic lexical route when reading words aloud. To investigate the
      mechanisms underlying her reading dysfunction, we analyzed her reading abilities
      using the Dual-Route Cascaded Model. Language tests resulted in low correct
      percentages for both reading comprehension and reading nonwords aloud, suggesting
      problems in the semantic system and the nonlexical route. Conversely, the patient
      showed high scores on the reading words aloud task. Although she failed to
      understand many inconsistent-atypical words in the reading comprehension test,
      she correctly read most words aloud, suggesting that she used the nonsemantic
      lexical route. In addition, the lexical reading route was analyzed in detail by
      using inconsistent-atypical Kanji words as stimuli. Finally, we analyzed her
      reading dysfunction compared with previous cases.

PMID- 29032700
TI  - Improving Depression Care for Adults With Serious Mental Illness in
      Underresourced Areas: Community Coalitions Versus Technical Support.
AB  - OBJECTIVE: Community Partners in Care (CPIC) was a group-randomized study of two
      approaches to implementing expanded collaborative depression care: Community
      Engagement and Planning (CEP), a coalition approach, and Resources for Services
      (RS), a technical assistance approach. Collaborative care networks in both arms
      involved health care and other agencies in five service sectors. This study
      examined six- and 12-month outcomes for CPIC participants with serious mental
      illness. METHODS: This secondary analysis focused on low-income CPIC participants
      from racial-ethnic minority groups with serious mental illness in underresourced
      Los Angeles communities (N=504). Serious mental illness was defined as self
      reported severe depression (>=20 on the Patient Health Questionnaire-8) at
      baseline or a lifetime history of bipolar disorder or psychosis. Logistic and
      Poisson regression with multiple imputation and response weights, controlling for
      covariates, was used to model intervention effects. RESULTS: Among CPIC
      participants, 50% had serious mental illness. Among those with serious mental
      illness, CEP relative to RS reduced the likelihood of poor mental health-related
      quality of life (OR=.62, 95% CI=.41-.95) but not depression (primary outcomes);
      reduced the likelihood of having homelessness risk factors and behavioral health
      hospitalizations; increased the likelihood of mental wellness; reduced specialty
      mental health medication and counseling visits; and increased faith-based
      depression visits (each p<.05) at six months. There were no statistically
      significant 12-month effects. CONCLUSIONS: Findings suggest that a coalition
      approach to implementing expanded collaborative depression care, compared with
      technical assistance to individual programs, may reduce short-term behavioral
      health hospitalizations and improve mental health-related quality of life and
      some social outcomes for adults with serious mental illness, although no evidence
      was found for long-term effects in this subsample.

PMID- 29032701
TI  - Parent-Reported Use of Interventions by Toddlers and Preschoolers With Autism
      Spectrum Disorder.
AB  - OBJECTIVE: This study examined services used by young children with autism
      spectrum disorder (ASD) and factors associated with use. METHODS: A retrospective
      observational study was conducted with baseline data for toddlers (under age
      three) and preschoolers (three to less than six years) with ASD enrolled in the
      Autism Speaks Autism Treatment Network registry from 2008 to 2013 (N=2,804).
      Parents' reports at enrollment of services received by children were documented.
      Factors associated with service use and with hours per week of services used were
      identified by multiple regression analyses. RESULTS: At baseline, 79% of children
      had received at least one service; 28% had received behavioral services. In the
      sample, less than 30% of children who received at least one service spent more
      than ten hours per week in any service use. Children who received services were
      more likely to be of white race and to have had an ASD diagnosis prior to
      registry enrollment. Age, previous ASD diagnosis, maternal education, and child's
      IQ were significantly associated with the use of behavioral services; IQ was
      negatively associated with use. A consistent trend toward greater use of
      behavioral services was found over the study period. Factors associated with
      hours of any services used per week included age, gender, race, maternal
      education, and clinical characteristics. The predicted average weekly service
      hours for children with ASD across registry sites ranged from 3.1+/-1.0 to 9.5+/
      2.1. CONCLUSIONS: Service use varied according to child, family, and system
      characteristics. More efforts should be focused on early intervention and on
      children with ASD who have low socioeconomic status and cognitive disability.

PMID- 29032702
TI  - A Change in Perspective: From Dual Diagnosis to Multimorbidity.
AB  - OBJECTIVE: There has been increasing interest within psychiatry in the concept of
      multimorbidity because psychiatric patients typically present with multiple
      concurrent disorders, these disorders mutually exacerbate one another, and their
      interaction shapes treatment options. Metrics have not been developed to document
      multimorbidity in psychiatric clinical practice. METHODS: Four classes of
      indicators relevant to multimorbidity were defined and evaluated among veterans
      treated in mental health specialty clinics nationally in the Veterans Health
      Administration (VHA) in fiscal year 2012. RESULTS: Of the 843,583 veterans with
      at least three visits to a specialty mental health clinic, 94.6% had more than
      one general medical or mental disorder and 77.6% had more than one mental
      disorder, compared with 30.6% with co-occurring psychiatric and substance use
      disorders. CONCLUSIONS: Real-world psychiatric care is more accurately approached
      from the multimorbidity perspective than from the perspective of principal, dual,
      or comorbid diagnoses.

PMID- 29032703
TI  - The Use of Telepsychiatry to Provide Cost-Efficient Care During Pediatric Mental
      Health Emergencies.
AB  - OBJECTIVE: This study evaluated a videoconference-based psychiatric emergency
      consultation program (telepsychiatry) at geographically dispersed emergency
      department (ED) sites that are part of the network of care of an academic
      children's hospital system. The study compared program outcomes with those of
      usual care involving ambulance transport to the hospital for in-person
      psychiatric emergency consultation prior to disposition to inpatient care or
      discharge home. METHODS: This study compared process outcomes in a cross
      sectional, pre-post design at five network-of-care sites before and after
      systemwide implementation of telepsychiatry consultation in 2015. Clinical
      records on 494 pediatric psychiatric emergencies included ED length of stay,
      disposition/discharge, and hospital system charges. Satisfaction surveys
      regarding telepsychiatry consultations were completed by providers and parents or
      guardians. RESULTS: Compared with children who received usual care, children who
      received telepsychiatry consultations had significantly shorter median ED lengths
      of stay (5.5 hours and 8.3 hours, respectively, p<.001) and lower total patient
      charges ($3,493 and $8,611, p<.001). Providers and patient caregivers reported
      high satisfaction with overall acceptability, effectiveness, and efficiency of
      telepsychiatry. No safety concerns were indicated based on readmissions within 72
      hours in either treatment condition. CONCLUSIONS: Measured by charges and time,
      telepsychiatry consultations for pediatric psychiatric emergencies were cost
      efficient from a hospital system perspective compared with usual care consisting
      of ambulance transport for in-person consultation at a children's hospital main
      campus. Telepsychiatry also improved clinical and operational efficiency and
      patient and family experience, and it showed promise for increasing access to
      other specialized health care needs.

PMID- 29032704
TI  - Addressing Barriers to Clozapine Underutilization: A National Effort.
AB  - Although clozapine has demonstrated unique efficacy for the treatment of
      seriously ill patients with refractory psychosis, its real-world use presents
      challenges to clinicians in a variety of settings, leading to its
      underutilization in the United States. The barriers include a lack of prescriber
      knowledge and confidence, negative prescriber attitudes, special monitoring
      requirements, administrative burden, unprepared health systems, and inadequate
      appreciation of clozapine's unique nature by policy makers and payers. In 2016,
      the National Association of State Mental Health Program Directors (NASMHPD)
      gathered a national team of expert clinicians and researchers to identify and
      address barriers to clozapine use. NASMHPD has since expanded the work group,
      which convenes monthly to continue addressing specific recommendations. This Open
      Forum describes the deliberations of the work group and urges practitioners,
      administrators, local and state governments, researchers, families, and patients
      to join similar efforts to promote better access to clozapine and improve the
      treatment management for patients receiving clozapine.

PMID- 29032705
TI  - A Mobile Application for Monitoring and Management of Depressed Mood in a
      Vulnerable Pregnant Population.
AB  - OBJECTIVE: This study tested whether a mood tracking and alert (MTA) mobile
      application (app) improved mental health care delivery in a high-risk obstetric
      population. METHODS: Pregnant women with depressive symptomatology at <32 weeks
      gestation were followed for eight weeks after randomization to a control patient
      portal (PP) app alone or with the MTA app. The MTA app monitored activity,
      assessed mood, and alerted obstetric providers of signs of worsening mood.
      RESULTS: Seventy-two women enrolled (PP, N=24; MTA, N=48). MTA users had
      significantly more contacts addressing mental health, and as gestational age
      increased, they rated ability to manage their own health significantly better
      than women in the control group. Women who received telephone contact from a
      provider triggered by an MTA app alert were significantly more likely to receive
      a mental health specialist referral. CONCLUSIONS: A mobile MTA app improved
      service delivery and patient engagement among patients with perinatal depression
      symptoms.

PMID- 29032706
TI  - Quality and Predictors of Diabetes Care Among Patients With Schizophrenia: A
      Danish Nationwide Study.
AB  - OBJECTIVE: Patients with schizophrenia have a high prevalence of diabetes, but
      data on diabetes care quality for these patients are limited. This nationwide
      study compared the quality of diabetes care among individuals with and without
      schizophrenia and identified predictors of care quality. METHODS: In a population
      based cohort study, 83,813 individuals with diabetes seen at hospital outpatient
      clinics between 2005 and 2013, including 669 with comorbid schizophrenia, were
      identified from Danish registries. High-quality diabetes care was defined as
      having received >=80% of guideline-recommended process performance measures.
      Variables assessed as predictors of diabetes care included patient-specific (sex,
      age, smoking, substance abuse, Global Assessment of Functioning score, and
      duration of schizophrenia), provider-specific (quality of schizophrenia care),
      and system-specific (annual patient contact volume of the diabetes clinic)
      factors. RESULTS: Compared with individuals with diabetes only, those with
      diabetes and schizophrenia were less likely to receive high-quality diabetes care
      (relative risk [RR]=.91, 95% confidence interval [CI]=.88-.95) and less likely to
      receive several individual process performance measures of diabetes care,
      including blood pressure monitoring (RR=.98, CI=.96-.99), treatment with
      antihypertensive drugs (RR=.83, CI=.70-.97) and angiotensin-converting
      enzyme/angiotensin II receptor inhibitors (RR=.72, CI=.55-.93), screening for
      albuminuria (RR=.96, CI=.93-.99), eye examination at least once every second year
      (RR=.97, CI=.94-.99), and foot examination (RR=.96, CI=.93-.99). Predictors of
      poor diabetes care among individuals with schizophrenia included documented drug
      abuse and low contact volume of the diabetes clinic. CONCLUSIONS: Individuals
      with schizophrenia received lower-quality diabetes care compared with those
      without schizophrenia. However, absolute differences in care were modest.

PMID- 29032708
TI  - Retraction Notice.

PMID- 29032707
TI  - Safety of Psychiatric Inpatients at the Veterans Health Administration.
AB  - OBJECTIVE: Although reducing adverse events and medical errors has become a
      central focus of the U.S. health care system over the past two decades both
      within and outside the Veterans Health Administration (VHA) hospital systems,
      patients treated in psychiatric units of acute care general hospitals have been
      excluded from major research in this field. METHODS: The study included a random
      sample of 40 psychiatric units from medical centers in the national VHA system.
      Standardized abstraction tools were used to assess the electronic health records
      from 8,005 hospitalizations. Medical record administrators screened the records
      for the presence of ten specific types of patient safety events, which, when
      present, were evaluated by physician reviewers to assess whether the event was
      the result of an error, whether it caused harm, and whether it was preventable.
      RESULTS: Approximately one in five patients experienced a patient safety event.
      The most frequently occurring events were medication errors (which include
      delayed and missed doses) (17.2%), followed by adverse drug events (4.1%), falls
      (2.8%), and assault (1.0%). Most patient safety events (94.9%) resulted in little
      harm or no harm, and more than half (56.6%) of the events were deemed
      preventable. CONCLUSIONS: Although patient safety events in VHA psychiatric
      inpatient units were relatively common, a great majority of these events resulted
      in little or no patient harm. Nevertheless, many were preventable, and the study
      provides data with which to target future initiatives that may improve the safety
      of this vulnerable patient population.

PMID- 29032709
TI  - Putative predictors of efficacy for immune checkpoint inhibitors in non-small
      cell lung cancer: facing the complexity of the immune system.
AB  - INTRODUCTION: In non-small-cell lung cancer (NSCLC) the recent introduction of
      immunotherapy in daily clinical practice produced a wave of enthusiasm, however,
      this was rapidly moderated by the evidence that only some patients could
      experience a relevant clinical benefit. Therefore, a great effort from the
      scientific community has been dedicated to the identification and validation of
      reliable biomarkers able to drive the activity of immunotherapeutic agents. Areas
      covered: This analysis aims to review the main findings about predictive
      biomarkers for immunotherapy in lung cancer, retracing the history of PD-L1 and
      focusing on a series of innovative candidates, such as mutational load, immune
      cell populations and microbiome. Expert commentary: Considering the complexity of
      the immune system-cancer interactions, the idea of identifying a single biomarker
      able to drive the activity of different immunotherapeutic agents alone, borrowing
      the idea of targeted therapy, is likely to represent an unrealistic objective.
      Nevertheless, the identification of those factors either positively or negatively
      affecting the response is mandatory in order to recruit the appropriate patients,
      but also to deeply understand the mechanisms of immune response and improve the
      clinical benefit deriving from these agents in monotherapy or in a biologically
      rationale combination.

PMID- 29032710
TI  - Phase I dose escalation study of the anti-CD2 monoclonal antibody, siplizumab,
      with DA-EPOCH-R in aggressive peripheral T-cell lymphomas.

PMID- 29032712
TI  - Retraction notice.
AB  - It has been brought to our attention that the following case report contains
      inaccuracies with regard to the case information presented. It has therefore been
      retracted from Future Cardiology, at the request of the authors. Murana G,
      Cefarelli M, Kloppenburg G, Morshuis WJ, Heijmen RH. Surgical exclusion of a
      saccular aneurysm within a patent ductus arteriosus in an adult patient with
      Ortner's syndrome. Future Cardiol. 12(6), 613-616 (2016).

PMID- 29032711
TI  - Identification of rosmarinic acid and sulfated flavonoids as inhibitors of
      microfouling on the surface of eelgrass Zostera marina.
AB  - A bioassay-guided approach was used to identify defense compounds that are
      present on the surface of Zostera marina and which inhibit settlement of
      microfoulers at natural concentrations. Moderately polar eelgrass surface
      extracts inhibited the settlement of seven marine bacteria and one yeast that
      originated from non-living substrata. In contrast, five other bacterial strains
      that had been directly isolated from eelgrass surfaces were all insensitive,
      which suggested a selective effect of surface metabolites on the microbial
      communities present on eelgrass. Bioassay-guided isolation of active compounds
      from the extracts in combination with UPLC-MS and 1H-NMR spectroscopy resulted in
      the identification of rosmarinic acid, luteolin-7-sulfate and diosmetin-7-sulfate
      or its isomer chrysoeriol-7-sulfate. All three compounds are nontoxic repellents,
      as they did not inhibit bacterial growth, but prevented bacterial settlement in a
      dose-dependent manner. Between 15.6 and 106.8 MUg ml-1 of rosmarinic acid were
      present on the eelgrass surface, enough for half maximal settlement inhibition of
      bacteria.

PMID- 29032713
TI  - Intravenous iron treatments for iron deficiency anemia in inflammatory bowel
      disease: a budget impact analysis of iron isomaltoside 1000 (Monofer) in the UK.
AB  - INTRODUCTION: Iron deficiency is the leading cause of anemia in patients with
      inflammatory bowel disease (IBD). Intravenous iron is the first-line treatment
      for clinically active IBD or previous oral iron intolerance. The aim of the
      present study was to develop a comparative model of iron deficiency and delivery
      for iron isomaltoside (IIM), ferric carboxymaltose (FCM), low molecular weight
      iron dextran (LMWID), and iron sucrose (IS) in the treatment of iron deficiency
      anemia associated with IBD. Areas covered: A model was developed to evaluate iron
      delivery characteristics, resource use and costs associated with IIM, FCM, LMWID
      and IS. Iron deficiency was modeled using dosing tables and retreatments were
      modeled based on a pooled retrospective analysis. The analyses were conducted
      over 5 years in patients with IBD with mean bodyweight of 75.4 kg and hemoglobin
      levels of 10.77 g/dL based on observational data. Expert opinion: The modeling
      analysis showed that using IIM required 1.2 infusions (per treatment) to correct
      the mean iron deficit, compared with 1.6, 1.2, and 7.1 with FCM, LMWID and IS,
      respectively. Costs were estimated to be 2,518 pounds sterling (GBP) per patient
      with IIM or LMWID, relative to GBP 3,309 with FCM or GBP 14,382 with IS.

PMID- 29032714
TI  - Fusion of optical coherence tomography and angiography for numerical simulation
      of hemodynamics in bioresorbable stented coronary artery based on patient
      specific model.
AB  - Three-dimensional simulations of coronary artery using finite element analysis
      are considered as effective means to understand the biomechanical properties
      after the stent was deployed. Bioresorbable vascular scaffolds are new-generation
      stents used by people. Intravascular optical coherence tomography is an emerging
      technique for detecting struts. The common 3 D reconstruction methods are using
      Intravascular Ultrasound (IVUS) or angiographies. However, it loses the details
      about geometry model. Fusing of optical coherence tomography and angiography to
      reconstruct the bioresorbable stented coronary artery based on patient-specific
      mode is an innovative method to reconstruct the high fidelity geometry. This
      study aimed to use computer-aided design models and computational fluid dynamics
      research tools to conduct a systematic investigation of blood flow in an isolated
      artery with realistically deployed coronary stents. Some important hemodynamic
      factors such as wall shear stress, wall pressure and streamline were calculated.
      The doctors could evaluate the local hemodynamic alterations within coronary
      arteries after stent deployment by reconstructing the high-fidelity geometry
      about each clinical case.

PMID- 29032715
TI  - Frequent consumption of sugar-sweetened beverages and sweets starts at early age.
AB  - OBJECTIVES: We aimed to investigate the habitual consumption of sugar-sweetened
      beverages (SSBs) and sweets in relation to mothers' behaviours and practices with
      their infants. METHODS: We targeted mothers with children 1-24 months (N = 200)
      visiting Public Child Health clinics in Finland. During routine visits mothers (N
      = 179) volunteered to complete a self-administered anonymous questionnaire about
      their child's health-related behaviours (consumption of sweets and SSBs, tooth
      brushing frequency). The questionnaires also included questions about the
      mothers' background (age, education) and health-related behaviours (consumption
      of sweets, tooth brushing frequency and smoking habits). The children were
      categorised by age, and Chi-squared tests, Fischer's exact test, ANOVA and
      correlation coefficient served for the statistical analyses. RESULTS: Of those
      under 6 months, almost half (44%) received SSBs, and 45% of them more than once a
      week. Their use gradually increased by age such that by 19-24 months, all
      received SSBs at least sometimes, and 56%, frequently. Fewer than half of the
      mothers (33-43%) gave sweets to their children between the ages of 10-15 months,
      but 92% by the age of 2 years. Children's twice-a-day tooth brushing increased
      from 14% to 33%. The child's age and tooth brushing frequency correlated with the
      consumption of sugar-sweetened products (r = 0.458). CONCLUSIONS: Infants
      frequent consumption of sugar-sweetened products begins early in childhood. Thus,
      tackling these common risk factors in the first years of life is essential and
      calls for health-promoting actions in multiple areas that target primarily the
      parents of infants.

PMID- 29032716
TI  - Prediction of coronary plaque progression using biomechanical factors and
      vascular characteristics based on computed tomography angiography.
AB  - OBJECTIVES: Coronary atherosclerotic plaques progress in a highly individual
      manner. Accurately predicting plaque progression will promote clinical management
      of atherosclerosis. The purpose of this study was to investigate the role of
      local biomechanics factors and vascular characteristics in coronary plaque
      progression and arterial remodeling. METHODS: Computed tomography angiography
      based three-dimensional reconstruction of the native right coronary artery was
      performed in vivo in twelve patients with acute coronary syndrome at baseline and
      12-month follow-up. The reconstructed arteries were divided into sequential 3-mm
      long segments. Wall shear stress (WSS) and von Mises stress (VMS) were computed
      in all segments at baseline by applying fluid-structure interaction simulations.
      RESULTS: In total, 365 segments 3-mm long were analyzed. The decrease in minimal
      lumen area was independently predicted by low baseline VMS (-0.73 +/- 0.13 mm2),
      increase in plaque burden was independently predicted by small minimal lumen area
      and low baseline WSS (6.28 +/- 0.96%), and decrease in plaque volume was
      independently predicted by low baseline VMS (-0.99 +/- 0.49 mm3). Negative
      remodeling was more likely to occur in low- (55%) and moderate-VMS (40%)
      segments, but expansive remodeling was more likely to occur in high-VMS (44%)
      segments. CONCLUSIONS: Local von Mises stress, wall shear stress, minimal lumen
      area, and plaque burden provide independent and additive prediction in
      identifying coronary plaque progression and arterial remodeling.

PMID- 29032717
TI  - BET inhibitors in metastatic prostate cancer: therapeutic implications and
      rational drug combinations.
AB  - INTRODUCTION: The bromodomain and extra-terminal (BET) family of proteins are
      epigenetic readers of acetylated histones regulating a vast network of protein
      expression across many different cancers. Therapeutic targeting of BET is an
      attractive area of clinical development for metastatic castration-resistant
      prostate cancer (mCRPC), particularly due to its putative effect on c-MYC
      expression and its interaction with the androgen receptor (AR). Areas covered: We
      speculate that a combination approach using inhibitors of BET proteins (BETi)
      with other targeted therapies may be required to improve the therapeutic index of
      BET inhibition in the management of prostate cancer. Preclinical data has
      identified several molecular targets that may enhance the effect of BET
      inhibition in the clinic. This review will summarize the known preclinical data
      implicating BET as an important therapeutic target in advanced prostate cancer,
      highlight the ongoing clinical trials targeting this protein family, and
      speculate on rationale combination strategies using BETi together with other
      agents in prostate cancer. A literature search using Pubmed was performed for
      this review. Expert opinion: Use of BETi in the treatment of mCRPC patients may
      require the addition of a second novel agent.

PMID- 29032718
TI  - State governance versus dentists' autonomy - the case of Swedish dental care.
AB  - OBJECTIVE: A trend towards the state governance of healthcare through quality
      indicators and national clinical guidelines has been observed, and it is argued
      that this trend can be a challenge to the autonomy of healthcare professionals.
      In Sweden, these regulatory tools have been implemented in combination with
      subsidies for adult dental care that are based on guideline recommendations which
      serve to ensure that dental care is evidence-based and cost-effective. This paper
      aims to analyse the implications of these changes regarding dentists' autonomy
      and whether the government's political intentions can be fulfilled. MATERIAL AND
      METHODS: The paper is based on documents from government authorities and
      professional theories. RESULTS: The financial control over Swedish dental care
      has been strengthened, and it can be argued that this is a step in the right
      direction from a societal point of view, as public resources are limited.
      Dentists' professional autonomy with their patients is not affected, which is
      appropriate, as patients should be treated according to their individual needs
      and expectations. CONCLUSIONS: This article shows that the state's governance
      does not directly detail dentists' work, which indicates a balance between state
      governance and dentists' autonomy. However, further research is required to get
      knowledge on Swedish dentists' view of the governance.

PMID- 29032719
TI  - Improved survival outcomes with the addition of rituximab to initial therapy for
      chronic lymphocytic leukemia: a comparative effectiveness analysis in the
      province of British Columbia, Canada.
AB  - Chemoimmunotherapy with rituximab improves survival in clinical trials in upfront
      chronic lymphocytic leukemia (CLL) treatment. This study compared clinical
      outcomes with and without rituximab added to first-line chemotherapy in a
      provincial cohort of CLL patients. Between 1973 and 2014, 1345 patients received
      CLL treatment: 48% with rituximab, 52% chemotherapy alone. Median overall
      survival (OS) and treatment-free survival (TFS) were significantly longer with
      rituximab: OS 8.9 vs. 6.2 years, p < .0001; TFS 3.6 vs. 2.1 years, p < .0001.
      Addition of rituximab to chemotherapy was a strong independent predictor of
      mortality with a 32% mortality reduction after controlling for co-variates (age,
      sex, stage, and treatment with purine analogs). This large population-based study
      complements clinical trial and registry data demonstrating the benefit of adding
      rituximab to first-line CLL therapy and adds further evidence of the efficacy of
      rituximab-based chemoimmunotherapy in a real-world setting.

PMID- 29032720
TI  - Effect of whole body vibration on spasticity in hemiplegic legs of patients with
      stroke.
AB  - BACKGROUND: Several reports have focused on the effects of whole body vibration
      (WBV) on spasticity with differing results. Most studies used modified Ashworth
      scale (MAS) for qualitative measurements, but the effect was small. OBJECTIVE: To
      investigate the effect of WBV on spasticity in hemiplegic legs of patients with
      stroke using F-wave parameters. METHODS: Sixteen patients with stroke (mean age,
      54.7 +/- 13.5 years: time after stroke, 28.0 +/- 26.3 months) were enrolled in a
      comparative before-and-after intervention trial. WBV was applied at 30 Hz (4-8 mm
      amplitude) for 5 min on the hamstrings, gastrocnemius, and soleus muscles in a
      sitting position. Spasticity was assessed according to the F-wave parameters,
      MAS, and active and passive range of motion (A-ROM and P-ROM, respectively).
      These assessments were obtained before, immediately after, and 20 min after each
      intervention. RESULTS: The F-wave parameters, MAS score, and P-ROM improved
      significantly after the WBV and remained below the baseline level, even after 20
      min; no such change was noted in the unaffected limb via the F-wave parameters.
      The WBV also improved volitional movement immediately after intervention, as
      indicated by the A-ROM. CONCLUSIONS: These results confirmed a significant
      reduction of motor neuron excitability until 20 min after the WBV, as indicated
      by F-wave parameters.

PMID- 29032721
TI  - Estimation of sensitivity and specificity of pregnancy diagnosis using
      transrectal ultrasonography and ELISA for pregnancy-associated glycoprotein in
      dairy cows using a Bayesian latent class model.
AB  - AIMS: To determine the sensitivity (Se) and specificity (Sp) of pregnancy
      diagnosis using transrectal ultrasonography and an ELISA for pregnancy-associated
      glycoprotein (PAG) in milk, in lactating dairy cows in seasonally calving herds
      approximately 85-100 days after the start of the herd's breeding period. METHODS:
      Paired results were used from pregnancy diagnosis using transrectal
      ultrasonography and ELISA for PAG in milk carried out approximately 85 and 100
      days after the start of the breeding period, respectively, from 879 cows from
      four herds in Victoria, Australia. A Bayesian latent class model was used to
      estimate the proportion of cows pregnant, the Se and Sp of each test, and
      covariances between test results in pregnant and non-pregnant cows. Prior
      probability estimates were defined using beta distributions for the expected
      proportion of cows pregnant, Se and Sp for each test, and covariances between
      tests. Markov Chain Monte Carlo iterations identified posterior distributions for
      each of the unknown variables. Posterior distributions for each parameter were
      described using medians and 95% probability (i.e. credible) intervals (PrI). The
      posterior median estimates for Se and Sp for each test were used to estimate
      positive predictive and negative predictive values across a range of pregnancy
      proportions. RESULTS: The estimate for proportion pregnant was 0.524 (95% PrI =
      0.485-0.562). For pregnancy diagnosis using transrectal ultrasonography, Se and
      Sp were 0.939 (95% PrI = 0.890-0.974) and 0.943 (95% PrI = 0.885-0.984),
      respectively; for ELISA, Se and Sp were 0.963 (95% PrI = 0.919-0.990) and 0.870
      (95% PrI = 0.806-0.931), respectively. The estimated covariance between test
      results was 0.033 (95% PrI = 0.008-0.046) and 0.035 (95% PrI = 0.018-0.078) for
      pregnant and non-pregnant cows, respectively. Pregnancy diagnosis results using
      transrectal ultrasonography had a higher positive predictive value but lower
      negative predictive value than results from the ELISA across the range of
      pregnancy proportions assessed. CONCLUSIONS AND CLINICAL RELEVANCE: Pregnancy
      diagnosis using transrectal ultrasonography and ELISA for PAG in milk had similar
      Se but differed in predictive values. Pregnancy diagnosis in seasonally calving
      herds around 85-100 days after the start of the breeding period using the ELISA
      is expected to result in a higher negative predictive value but lower positive
      predictive value than pregnancy diagnosis using transrectal ultrasonography.
      Thus, with the ELISA, a higher proportion of the cows with negative results will
      be non-pregnant, relative to results from transrectal ultrasonography, but a
      lower proportion of cows with positive results will be pregnant.

PMID- 29032723
TI  - Re: Farm and cow-level prevalence of bovine digital dermatitis on dairy farms in
      Taranaki, New Zealand.

PMID- 29032722
TI  - Comparison of fermented animal feed and mushroom growth media as two value-added
      options for waste Cassava pulp management.
AB  - Cassava is one of the main processed crops in Thailand, but this generates large
      amounts (7.3 million tons in 2015) of waste cassava pulp (WCP). The solid WCP is
      sold directly to farmers or pulp-drying companies at a low cost to reduce the
      burden of on-site waste storage. Using an integrated direct and environmental
      cost model, fermented animal feed and mushroom growth media were compared as
      added-value waste management alternatives for WCP to mitigate environmental
      problems. Primary and secondary data were collected from the literature, field
      data, and case studies. Data boundaries were restricted to a gate-to-gate
      scenario with a receiving capacity of 500 t WCP/d, and based on a new production
      unit being set up at the starch factory. The total production cost of each WCP
      utilization option was analyzed from the economic and environmental costs.
      Fermented animal feed was an economically attractive scenario, giving a higher
      net present value (NPV), lower investment cost and environmental impact, and a
      shorter payback period for the 10-year operational period. The selling price of
      mushrooms was the most sensitive parameter regarding the NPV, while the NPV for
      the price of fermented animal feed had the highest value in the best-case
      scenario.

PMID- 29032725
TI  - Percutaneous pedestals in cochlear implantation.
AB  - Percutaneous pedestals have been integral to the development of cochlear implants
      since 1969. By enabling direct electrical access to implanted electrodes or other
      devices, they allow optimization of control of stimulation strategies. Similarly,
      technology not validated for implantable use can be safely tested. These
      advantages have facilitated the development of cochlear implants and also
      resulted in their inclusion in trials investigating electronic implants developed
      for other organs. Surgery is straightforward, but post-operative care, in
      particular, skin-care is crucial to ensure complications are minimized. This
      review discusses the history of percutaneous pedestal use in cochlear implants
      and other electronic devices. Surgical technique, aftercare, and complications of
      surgery are discussed along with possibilities for future development.

PMID- 29032724
TI  - Reintroducing the Sodium-Iodide Symporter to Anaplastic Thyroid Carcinoma.
AB  - BACKGROUND: Anaplastic thyroid carcinoma (ATC), the most aggressive form of
      thyroid cancer, is unresponsive to radioiodine therapy. The current study aimed
      to extend the diagnostic and therapeutic application of radioiodine beyond the
      treatment of differentiated thyroid cancer by targeting the functional sodium
      iodide symporter (NIS) to ATC. METHODS: The study employed nanoparticle vectors
      (polyplexes) based on linear polyethylenimine (LPEI), shielded by polyethylene
      glycol (PEG) and coupled to the synthetic peptide GE11 as an epidermal growth
      factor receptor (EGFR)-specific ligand in order to target a NIS-expressing
      plasmid (LPEI-PEG-GE11/NIS) to EGFR overexpressing human thyroid carcinoma cell
      lines. Using ATC xenograft mouse models, transfection efficiency by 123I
      scintigraphy and potential for systemic radioiodine therapy after systemic
      polyplex application were evaluated. RESULTS: In vitro iodide uptake studies in
      SW1736 and Hth74 ATC cells, and, for comparison, in more differentiated
      follicular (FTC-133) and papillary (BCPAP) thyroid carcinoma cells demonstrated
      high transfection efficiency and EGFR-specificity of LPEI-PEG-GE11/NIS that
      correlated well with EGFR expression levels. After systemic polyplex injection,
      in vivo 123I gamma camera imaging revealed significant tumor-specific
      accumulation of radioiodine in an SW1736 and an Hth74 xenograft mouse model.
      Radioiodine accumulation was found to be higher in SW1736 tumors, reflecting in
      vitro results, EGFR expression levels, and results from ex vivo analysis of NIS
      staining. Administration of 131I in LPEI-PEG-GE11/NIS-treated SW1736 xenograft
      mice resulted in significantly reduced tumor growth associated with prolonged
      survival compared to control animals. CONCLUSIONS: The data open the exciting
      prospect of NIS-mediated radionuclide imaging and therapy of ATC after non-viral
      reintroduction of the NIS gene. The high tumor specificity after systemic
      application makes the strategy an attractive alternative for the treatment of
      highly metastatic ATC.

PMID- 29032726
TI  - Effect of macro- and micro-nutrients addition during anaerobic mono-digestion of
      grass silage in leach-bed reactors.
AB  - The effect of macro- (NH4Cl) (set I) and micro-nutrients (Fe, Ni, Co and Mo) (set
      II) addition on chemical oxygen demand (COD) solubilisation during anaerobic mono
      digestion of grass silage was investigated in two sets of leach bed reactor
      experiments at 35 degrees C. Results showed that addition of NH4Cl and micro
      nutrients improved COD solubilisation by 18% (0.56 g SCOD g-1 volatile solids)
      and 7% (0.45 g SCOD g-1 VS), respectively than control. About 20-50% of the added
      micro-nutrients were bioavailable in the produced leachates, while the rest (50
      80%) were adsorbed onto the grass silage. Results of biological methane potential
      assays showed that, specific methane yields of grass silage were improved by 17%
      (0.36 +/- 0.02 m3 CH4 kg-1 VSadded) when NH4Cl was supplemented while Fe, Ni, Co
      and Mo addition improved methane yields by 15% (0.33 +/- 0.005 m3 CH4 kg-1
      VSadded) when compared to control.

PMID- 29032727
TI  - Spleen-Derived Anti-Inflammatory Cytokine IL-10 Stimulated by Adipose Tissue
      Derived Stem Cells Protects Against Type 2 Diabetes.
AB  - Considering that the spleen plays an important role in the occurrence and
      development of diabetes, we aimed at investigating the role of the spleen in the
      treatment of type 2 diabetes (T2D) with adipose tissue-derived stem cells
      (ADSCs). We established a T2D/splenectomy (SPX) rat model by using high-fat
      diet/streptozotocin administration with SPX, assessed the therapeutic effects of
      ADSCs, and explored the possible mechanism. A single ADSC infusion was found to
      ameliorate hyperglycemia and insulin resistance in diabetic rats, accompanied by
      a considerable number of ADSCs homing to the spleens in T2D rats. Moreover, four
      times of infusion of ADSCs resulted in a more significant reduction of blood
      glucose and insulin resistance, whereas SPX exacerbated hyperglycemia and insulin
      resistance and attenuated the effects of ADSCs. In addition, ADSC infusion
      promoted anti-inflammatory cytokine interleukin (IL)-10 expression and inhibited
      pro-inflammatory cytokines IL-6, IL-1beta, and tumor necrosis factor (TNF)-alpha
      expression in both the spleen and serum of T2D rats without SPX. ADSCs also
      inhibited serum IL-6, IL-1beta, and TNF-alpha expression, but cannot promote IL
      10 expression in T2D rats with SPX. Therefore, these data indicate that the
      effect of ADSCs ameliorating hyperglycemia and insulin resistance may be
      partially through promoting spleen-derived anti-inflammatory cytokine IL-10
      expression. These novel findings further confirmed the essential role of the
      spleen in the ADSC treatment of T2D and provide an important theoretical basis
      for the potential application of ADSCs in T2D therapy.

PMID- 29032728
TI  - Estrogen receptor beta expression and prognosis of diffuse large B cell lymphoma.
AB  - OBJECTIVES: Estrogen receptor beta (ERbeta)-selective agonists inhibited B cell
      lymphoma growth in animal models. However, a recent study found that higher
      ERbeta expression in tissue from diffuse large B cell lymphoma (DLBCL) patients
      indicated a poorer survival. This study aimed to determine the ERbeta expression
      in DLBCL tissue using immunohistochemistry and correlate with clinical outcomes.
      METHODS: Diagnostic tissues from newly diagnosed adult DLBCL patients treated
      with Rituximab-Cyclophosphamide/Doxorubicin/Vincristine/Prednisolone were counted
      for ERbeta1-expressing cells. Nodal lymphoma (N = 41) was analyzed separately
      from extra-nodal DLBCL (N = 31). RESULTS: On immunohistochemistry, ERbeta1 was
      expressed in 73.6% of cases with the median expressing cells of 20%. For nodal
      lymphoma, high ERbeta expression (>=25%) was associated with poorer event free
      survival (EFS) independent of the international prognostic index with the
      adjusted hazard ratio (HR) of 2.49 (95% Confidence interval (CI) 1.03-6.00, P =
      0.042). On the contrary, high ERbeta expression (>=25%) was associated with
      superior outcomes in extra-nodal DLBCL with the adjusted HR of 0.25 (95% CI 0.09
      0.75, P = 0.013) for EFS and adjusted HR of 0.29 (95% CI 0.10-0.85, P = 0.024)
      for overall survival in multivariate analyses. CONCLUSION: ERbeta1 protein
      expression represented opposite prognostic factors in nodal vs. extra-nodal
      DLBCL.

PMID- 29032729
TI  - Impact of inserted long rest periods during repeated sprint exercise on
      performance adaptation.
AB  - Repeated sprint training consists of a series of brief maximal sprints, 3-7 s in
      duration, separated by short rest periods of <60 s. However, little is known
      about the influence of different rest period lengths between sprints on
      performance adaptation. We determined the influence of inserting long rest
      periods during repeated sprint training on performance adaptation in competitive
      athletes. Twenty-one well-trained athletes were separated into either the short
      rest period group (SHORT; n = 10) or the long rest period group (LONG; n = 11).
      The training protocol for both groups consisted of two sets of 12 * 6-s maximal
      cycle sprints with 24 s of rest between sprints. However, in the LONG group, an
      active rest period of 7 min was inserted every three sprints to attenuate the
      power output decrement during the latter half of the sprints. The training was
      performed 3 d/week for 3 weeks. Before and after the training period, repeated
      sprint ability [12 * 6-s maximal sprint (pedaling) with 24-s rest] was evaluated.
      Maximal power output during the repeated sprint test was significantly increased
      only in the LONG group (P < .05). Both groups showed a similar increase in power
      output during the latter half of sprints (P < .05). The LONG group showed a
      significant increase in [Formula: see text] (P < .05). These results suggest that
      repeated sprint training with insertion of longer rest periods is an efficient
      strategy for improving maximal power output compared with the same training
      separated by short rest periods alone.

PMID- 29032730
TI  - Biological groundwater treatment for hexavalent chromium removal at low chromium
      concentrations under anoxic conditions.
AB  - The objective of this work is to evaluate biological groundwater treatment
      systems that will achieve hexavalent chromium removal from groundwater at
      hexavalent chromium (Cr(VI)) groundwater concentrations in the 0-200 MUg/L range
      under anoxic conditions. The effect of type of organic substrate added as feed to
      the groundwater treatment system (milk, sugar and cheese whey), the effect of
      different concentrations of chemical oxygen demand added in the feed (100, 150
      and 200 mg/L) and the effect of different hydraulic residence time (1.7, 0.9 and
      0.7 d) on process performance were evaluated through the operation of a series of
      sequential batch reactors under anoxic conditions. Biomass receiving Cr(VI)
      contaminated groundwater with a low nitrates content exhibited similar Cr(VI)
      removal efficiency under reductive conditions, with biomass receiving Cr(VI)
      contaminated groundwater with a high nitrates content. The concentration of
      organic substrate was crucial for the microbial reduction of Cr(VI). The
      different hydraulic residence time of the reactors and the different types of
      organic substrates added did not affect the efficiency of hexavalent chromium
      removal which was complete. This study demonstrates that biological systems
      operating under reductive conditions can efficiently treat groundwater containing
      low or high nitrates concentration and can provide complete hexavalent chromium
      removal at initial Cr(VI) concentrations of 200 MUg/L.

PMID- 29032731
TI  - Cytogenetic risk stratification may predict allogeneic hematopoietic stem cell
      transplantation outcomes for chronic myelomonocytic leukemia.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only
      curative treatment for chronic myelomonocytic leukemia (CMML); however, factors
      predicting allo-HSCT outcomes for CMML have not been well defined. This study
      assessed whether the existing five scoring systems for CMML prognosis could be
      applied for predicting allo-HSCT outcomes. We retrospectively evaluated 38
      patients who underwent allo-HSCT for CMML from 2000 to 2014. At 3 years, overall
      survival (OS) and disease-free survival were 34.6 and 24.7%, respectively.
      According to the risk stratification at the time of transplantation, only the
      CMML-specific cytogenetic risk scoring system could successfully predict
      transplantation outcomes. At 3 years, OS was 56.7, 12.5, and 0% (p = .01) in the
      low, intermediate, and high-risk groups. Our data suggest that the CMML-specific
      cytogenetic risk stratification at transplant may be useful for identifying
      patients with CMML who may benefit from HSCT. However, further studies are
      warranted to confirm this observation.

PMID- 29032732
TI  - A Personalized Week-to-Week Updating Algorithm to Improve Continuous Glucose
      Monitoring Performance.
AB  - BACKGROUND: Continuous glucose monitoring (CGM) systems are increasingly becoming
      essential components in type 1 diabetes mellitus (T1DM) management. Current CGM
      technology requires frequent calibration to ensure accurate sensor performance.
      The accuracy of these systems is of great importance since medical decisions are
      made based on monitored glucose values and trends. METHODS: In this work, we
      introduce a calibration strategy that is augmented with a weekly updating
      feature. During the life cycle of the sensor, the calibration mechanism
      periodically estimates the parameters of a calibration model to fit self
      monitoring blood glucose (SMBG) measurements. At the end of each week of use, an
      optimization problem that minimizes the sum of squared residuals between past
      reference and predicted blood glucose values is solved remotely to identify
      personalized calibration parameters. The newly identified parameters are used to
      initialize the calibration mechanism of the following week. RESULTS: The proposed
      method was evaluated using two sets of clinical data both consisting of 6 weeks
      of Dexcom G4 Platinum CGM data on 10 adults with T1DM (over 10 000 hours of CGM
      use), with seven SMBG data points per day measured by each subject in an
      unsupervised outpatient setting. Updating the calibration parameters using the
      history of calibration data indicated a positive trend of improving CGM
      performance. CONCLUSIONS: Although not statistically significant, the updating
      framework showed a relative improvement of CGM accuracy compared to the non
      updating, static calibration method. The use of information collected for longer
      periods is expected to improve the performance of the sensor over time.

PMID- 29032733
TI  - CAR-T cells and allogeneic hematopoietic stem cell transplantation for
      relapsed/refractory B-cell acute lymphoblastic leukemia.
AB  - Relapsed/refractory acute lymphoblastic leukemia (ALL) has a low remission rate
      after chemotherapy, a high relapse rate and poor long-term survival even when
      allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed.
      Chimeric antigen receptors redirected T cells (CAR-T cells) can enhance disease
      remission with a favorable outcome for relapsed/refractory ALL, though some cases
      quickly relapsed after CAR-T cell treatment. Thus, treatment with CAR-T cells
      followed by allo-HSCT may be the best way to treat relapsed/refractory ALL. In
      this review, we first discuss the different types of CAR-T cells. We then discuss
      the treatment of relapsed/refractory ALL using only CAR-T cells. Finally, we
      discuss the use of CAR-T cells, followed by allo-HSCT, for the treatment of
      relapsed/refractory ALL.

PMID- 29032734
TI  - Gammaplex(r) 5 and 10% in the treatment of primary immunodeficiency and chronic
      immune thrombocytopenic purpura.
AB  - Immunoglobulin G is used to both prevent infection in primary immunodeficiency
      diseases (PIDs) and prevent bleeding in immune thrombocytopenic purpura.
      Gammaplex is a highly purified human intravenous immunoglobulin G available as 5
      and 10% liquid formulations. Gammaplex 5% has proven efficacy and safety in PID
      and immune thrombocytopenic purpura, protecting against serious acute bacterial
      infections and treating bleeding by improving platelet counts, respectively. The
      therapeutic effect of Gammaplex 10% is expected to be similar to that of
      Gammaplex 5% based on demonstrated bioequivalence in a bridging study in PID. The
      availability of Gammaplex 10% provides another option to individualize therapy
      according to patient needs, allowing a 34% reduction in infusion time without
      compromising safety and tolerability.

PMID- 29032735
TI  - Sarcoidosis, malignancy and immune checkpoint blockade.

PMID- 29032737
TI  - Melanoma: a prototype of cancer-testis antigen-expressing malignancies.
AB  - Melanoma is the first malignancy in which expression and immunogenicity of cancer
      testis antigens (CTAs) have been documented. Several CTAs have been shown to be
      expressed in melanoma samples especially those with metastatic potential. Many of
      them have been shown to exert oncogenic effects through modulation of essential
      pathways involved in melanoma. The crucial role of CTAs in the pathogenesis of
      melanoma, the high prevalence of expression of CTA panels in melanoma and the
      presence of spontaneous as well as inducible immune responses against CTAs in
      melanoma patients potentiate CTAs as immunotherapeutic targets. Numerous clinical
      trials are now ongoing to evaluate CTA-based immunotherapeutic effects in
      melanoma patient's survival. NY-ESO-1 and MAGE antigens have the most promising
      results up to now.

PMID- 29032736
TI  - Coccidioidomycosis, immunoglobulin deficiency: safety challenges with CAR T cells
      therapy for relapsed lymphoma.
AB  - Treatment of patients with relapsed or refractory lymphoma may require allogenic
      hematopoietic stem cell transplant (HSCT), but treatment of post-transplant
      relapse disease remains very challenging. Donor lymphocyte infusion and
      blinatumomab have been used with limited success for the treatment of relapse.
      Initial data on donor-derived CAR T cells has shown this modality to be safe and
      highly effective in various hematological malignancies. We present a case of a
      patient with highly refractory, transformed follicular lymphoma who failed both
      autologous and allogenic HSCT. Patient achieved long-lasting complete remission
      with the use of donor origin CD19 CAR T-cell therapy, without any evidence of
      graft-versus-host disease flare. Our patient later developed disseminated
      coccidioidomycosis and persistent hypogammaglobulinemia. Immunotherapy using CD19
      CAR T cells can be a highly effective salvage modality, especially in cases of
      focal lymphoma relapse. Long-term immunosuppression secondary to B cell
      lymphopenia, hypogammaglobulinemia, immunoglobulin subclass deficiency, fungal
      infections and other infectious complications need to be monitored and promptly
      treated as indicated.

PMID- 29032738
TI  - Long-term survival in a patient with low-level inflammatory markers and liver
      metastasis, converted resectable by TACE.
AB  - Case report presents the successful treatment of unresectable liver metastasis in
      a patient with colon cancer. A 44-year-old male underwent right hemicolectomy
      followed by capecitabine for a moderately differentiated adenocarcinoma of the
      colon. 2 years later, a liver metastatic lesion was detected and had increased in
      size despite chemotherapy with capecitabine plus oxaliplatin (XELOX). Curative
      liver resection was conducted after conversion of unresectable tumor to
      resectable by transarterial chemoembolization followed by chemotherapy -
      irinotecan with fluorouracil and folinic acid (FOLFIRI). No recurrence was
      observed during 22-month follow-up after hepatectomy.

PMID- 29032739
TI  - Live Leishmania tarentolae secreting HNP1 as an immunotherapeutic tool against
      Leishmania infection in BALB/c mice.
AB  - AIM: Several disadvantages about chemotherapy for leishmaniasis has reinforced
      discovery of novel therapeutic agents especially immunotherapeutics. HNP1, as a
      member of the mammalian antimicrobial peptides family, is an attractive molecule
      due to its broad functional spectrum. Here, the in vivo potency of HNP1 in
      transgenic Leishmania tarentolae as an immunotherapy tool against Leishmania
      major-infected BALB/c mice was examined. METHODS & RESULTS: 3 weeks after
      infection with L. major, the treatment effect of L. tarentolae-HNP1-EGFP was
      pursued. The results were promising in respect to parasite load control and Th1
      immune response polarization compared with controls. CONCLUSION: Immunotherapy by
      live L. tarentolae secreting HNP1 can elicit cellular immune response in a
      susceptible mouse model in order to control L. major infection.

PMID- 29032740
TI  - Editor's presentation.

PMID- 29032741
TI  - Titrated extract of Centella asiatica increases hair inductive property through
      inhibition of STAT signaling pathway in three-dimensional spheroid cultured human
      dermal papilla cells.
AB  - Dermal papilla (DP) is a pivotal part of hair follicle, and the smaller size of
      the DP is related with the hair loss. In this study, we investigated the effect
      of titrated extract of Centella asiatica (TECA) on hair growth inductive property
      on 3D spheroid cultured human DP cells (HDP cells). Significantly increased
      effect of TECA on cell viability was only shown in 3D sphered HPD cells, not in
      2D cultured HDP cells. Also, TECA treatment increased the sphere size of HDP
      cells. The luciferase activity of STAT reporter genes and the expression of STAT
      targeted genes, SOCS1 and SOCS3, were significantly decreased. Also, TECA
      treatment increased the expression of the hair growth-related signature genes in
      3D sphered HDP cells. Furthermore, TECA led to downregulation of the level of
      phosphorylated STAT proteins in 3D sphered HDP cells. Overall, TECA activates the
      potential of hair inductive capacity in HDP cells.

PMID- 29032742
TI  - Enhanced cyanide biodegradation by immobilized crude extract of Rhodococcus UKMP
      5M.
AB  - The capability of the crude extract of Rhodococcus UKMP-5M was enhanced by
      adopting the technology of immobilization. Among the matrices screened to
      encapsulate the crude extract, gellan gum emerged as the most suitable
      immobilization material, exceeding the activity of cyanide-degrading enzyme by
      61% and 361% in comparison to alginate carrier and non-immobilized crude extract,
      respectively. Improved bead mechanical strength which supported higher
      biocatalyst activity by 63% was observed when concentration of gellan gum,
      concentration of calcium chloride, number of beads and bead size were optimized.
      The immobilized crude extract demonstrated higher tolerance towards broad range
      of pH (5-10) and temperature (30 degrees C-40 degrees C), superior cyanide
      degrading activity over time and improved storage stability by maintaining 76% of
      its initial activity after 30 days at 4 degrees C. Furthermore, repeated use of
      the gellan gum beads up to 20 batches without substantial loss in the catalytic
      activity was documented in the present study, indicating that the durability of
      the beads and the stability of the enzyme are both above adequate. Collectively,
      the findings reported here revealed that the utilization of the encapsulated
      crude extract of Rhodococcus UKMP-5M can be considered as a novel attempt to
      develop an environmentally favourable and financially viable method in cyanide
      biodegradation.

PMID- 29032743
TI  - Adverse outcomes of sick leave due to mental disorders: A prospective study of
      discordant twin pairs.
AB  - AIMS: The aim of this study was to investigate whether sick leave due to
      different mental disorders increased the risk of reoccurring sick-leave,
      disability pension and unemployment, taking genetics and shared environment into
      account. METHODS: This register-based cohort study contains 2202 discordant twin
      pairs 18-64 years old, where one twin had sick leave due to a mental disorder
      2005-2006. The end of the sick-leave spell was the start of follow-up for both
      twins. The twins were followed up for reoccurring sick-leave, disability pension
      and unemployment (> 180 days in a year), until December 2012. Analyses were
      censored for disability pension, death, emigration and old-age pension. Cox
      proportional hazards models with time-varying covariates were used to calculate
      hazard ratios with 95% confidence intervals (CI). RESULTS: Those with sick leave
      due to mental disorders had a 3.64 (CI: 3.24-4.08) times higher risk of
      reoccurring sick-leave within the first two years; after that, hazard ratios were
      attenuated and explained by genetic factors. The first year, they had 12.24 (CI:
      8.11-18.46) times the risk of disability pension. The risk was attenuated but
      remained at 2.75 (CI: 2.07-3.65) after one year. The risk of unemployment was
      1.99 (CI: 1.72-2.31) during the whole follow-up period. The risk of unemployment
      and disability pension was lower for those with stress-related than other mental
      disorders, this was less clear for recurrent reoccuring sick-leave. CONCLUSIONS:
      Sick leave due to mental disorders increased the risk of reoccurring sick-leave
      within two years, disability pension and unemployment, independent of genetics
      and shared environment.

PMID- 29032745
TI  - * Strategic Directions in Osteoinduction and Biomimetics.

PMID- 29032744
TI  - Acoustic simulation of cochlear implant hearing: Effect of manipulating various
      acoustic parameters on intelligibility of speech.
AB  - OBJECTIVE: Cochlear implants process the acoustic speech signal and convert it
      into electrical impulses. During this processing, many parameters contribute to
      speech perception. The available literature reviewed the effect of manipulating
      one or two such parameters on speech intelligibility, but multiple parameters are
      seldom manipulated. METHOD: Acoustic parameters, including pulse rate, number of
      channels, 'n of m', number of electrodes, and channel spacing, were manipulated
      in acoustic simulations of cochlear implant hearing and 90 different combinations
      were created. Speech intelligibility at sentence level was measured using
      subjective and objective tests. RESULTS: Principal component analysis was
      employed to select only those components with maximum factor loading, thus
      reducing the number of components to a reasonable limit. Perceptual speech
      intelligibility was maximum for signal processing manipulation with respect to 'n
      of m' and rate of pulses/sec. Regression analysis revealed that lower rate (=500
      pps/ch) and lesser stimulating electrodes per cycle (2-4) contributed maximally
      for speech intelligibility. Perceptual estimate of speech quality (PESQ) and
      composite measures of spectral weights and likelihood ratio correlated with
      subjective speech intelligibility scores. DISCUSSION: The findings are consistent
      with the literature review, indicating that lesser stimulated channel per cycle
      reduces electrode interaction and hence improve spectral resolution of speech.
      Reduced rate of pulses/second enhances temporal resolution of speech. Thus, these
      two components contribute significantly to speech intelligibility. CONCLUSION:
      Pulse rate/channel and 'n of m' contribute maximally to speech intelligibility,
      at least in simulations of electric hearing.

PMID- 29032746
TI  - Truncated JFH1 E2 Protein: Is it Reliable to be Used in Diagnostic ELISA Test and
      as a Protein-Based Vaccine Candidate?
AB  - BACKGROUND: HCV E2 glycoprotein is one of the most attractive proteins for
      designing an effective vaccine. Deletion of hydrophobic carboxyl-terminal region
      of this protein is necessary for its secretion, especially when it is expressed
      in E-coli. In this study we expressed this protein in truncated form and
      evaluated its application in developing an ELISA test and induction of humoral
      response in immunized mice. OBJECTIVES: The purpose of this study was expression
      of HCV truncated E2 protein from JFH1 strain in E-coli BL21(DE3) and evaluation
      of its antigenicity. METHODS: Truncated E2 region from HCV genotype 2a (JFH1) was
      amplified by PCR and cloned into a pET28a (+) vector and was used to transform
      the E-coli DH5alpha strain. The recombinant E2 protein was evaluated both in an
      ELISA test and induction of humoral immunity in mice. RESULTS: Truncated E2
      protein was expressed in BL21(DE3). Its specific antibody was detected in serum
      samples from HCV infected patients. Also, it could elicit a significant humoral
      immunity in mice. CONCLUSION: Truncated form of E2 protein which has been
      expressed in E-coli could be used as an effective antigen both in diagnostic
      tests such as ELISA and also, as a protein-based vaccine candidate.

PMID- 29032747
TI  - Development of Potential Small Molecule Therapeutics for Treatment of Ebola
      Virus.
AB  - Ebola virus has caused 26 outbreaks in 10 different countries since its
      identification in 1976, making it one of the deadliest emerging viral pathogens.
      The most recent outbreak in West Africa from 2014-16 was the deadliest yet and
      culminated in 11,310 deaths out of 28,616 confirmed cases. Currently there are no
      FDA-approved therapeutics or vaccines to treat Ebola virus infections. The slow
      development of effective vaccines combined with the severity of past outbreaks
      emphasizes the need to accelerate research into understanding the virus lifecycle
      and the development of therapeutics for post exposure treatment. Here we present
      a summary of the major findings on the Ebola virus replication cycle and the
      therapeutic approaches explored to treat this devastating disease. The major
      focus of this review is on small molecule inhibitors.

PMID- 29032748
TI  - Mechanistic Understanding of Herbal Therapy in Inflammatory Bowel Disease.
AB  - The incidence and prevalence of inflammatory bowel diseases (IBD), which comprise
      ulcerative colitis and Crohn's disease, are increasing dramatically worldwide.
      Immunomodulators and biological agents can help but cause severe side effects in
      long-term use. As such, complementary and alternative medicine, in particular
      herbal remedy, is becoming more and more popular in the treatment of IBD
      patients. Many natural compounds have been used in clinical trials and some have
      been proven promising in IBD treatment. To achieve a better understanding of
      herbal therapy, researchers focus on understanding the underlying mechanisms by
      using experimental rodent models. The mechanism of the pathogenesis of IBD is
      complex involving both environmental and genetic factors. IBD is considered as a
      consequence of impaired epithelial barrier function, gut microbiota dysbiosis,
      and aberrant immune response. Studies have demonstrated that herbal medicine can
      improve epithelial proliferation and barrier integrity, restore microbiota
      homeostasis, and suppress hyper-immune reaction. This review is to summarize
      current understanding of the molecular basis of herbal treatment of IBD at the
      levels of epithelial, microbial, and immune regulation.

PMID- 29032749
TI  - Drug Metabolism as an Object of Computational Analysis by the Monte Carlo Method.
AB  - BACKGROUND: Metabolism of therapeutic agents in organism is extremely important
      from a point of view of drug discovery. Unfortunately, experimental estimation of
      phenomena related to metabolism is available for the limited number of
      substances. Under such circumstances, the development of computational method to
      predict endpoints related to metabolism of therapeutic agents becomes an
      attractive alternative for expensive and timeconsuming experiments. METHOD: A
      group of semi-empirical calculations are a convenient compromise between a
      necessity to carry out experiments and the desire to involve in the practical
      analysis of a bigger amount of molecular features related to the impact of
      different substances on metabolism. The practical organization of the
      investigational analysis may be based on the Monte Carlo technique. RESULTS: The
      statistical quality of predictive models built up with the Monte Carlo method is
      usually quite satisfactory. Thus, the semi-empirical calculation using the Monte
      Carlo method may extend available database, which are related to metabolism of
      different therapeutic agents. It should be noted that the above approach involves
      minimal animal testing. The CORAL software has been used for the calculations.
      CONCLUSION: The described approach based on the Monte Carlo technique is a tool
      to predict behavior of therapeutic agents in organism. The approach is flexible:
      small and large molecules (peptides) can be studied by means of building up
      models of their endpoints which have impact upon metabolism phenomena.

PMID- 29032750
TI  - Longitudinal Neuropsychological Outcome in Taiwanese Alzheimer's Disease Patients
      Treated with Medication.
AB  - BACKGROUND: The longitudinal change of neuropsychological tests (NPTs) in treated
      Alzheimer's disease (AD) is essential to understand the interplay of a
      therapeutic response from medication and a disease decline due to degenerative
      processes. The aim of our study is to investigate the annual cognitive
      progression as measured by commonly used NPTs in treated AD patients and to
      assess the potential predictors of disease progression. METHODS: Participants
      (N=455) diagnosed with AD and treated with cholinesterase inhibitors (ChEIs) or
      memantine at memory clinics in three hospitals in southern Taiwan from January
      2009 to December 2014 were enrolled in this prospectively registered study. The
      mean follow-up duration was 3.2 +/- 0.9 years. The patients' severity of AD
      ranged from very mild (clinical dementia rating (CDR) scales = 0.5) to moderate
      (CDR = 2.0). At baseline and for each year, participants were assessed by various
      NPTs commonly used in clinical practice, including the Mini-Mental State
      Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), CDR and CDR
      sum of boxes (CDR-SB). All enrolled participants were assessed for at least two
      years during follow-up. We used mixed-effect models to examine annual progression
      in the whole group and to compare the cognitive progression between the subgroups
      with very mild AD and mild to moderate AD. Potential predictors of disease
      progression, including age, gender, the type of ChEI, and Apolipoprotein E (APOE)
      genotype, were also analyzed. RESULTS: Among the study population, the rate of
      change in MMSE scores were -1.15 points per year, CASI scores were -4.27 points
      per year, and CDR-SB scores were 0.81 points per year. The slope of annual
      changes of NPTs differed significantly between the CDR 0.5 group and the CDR 1 to
      2 group. The most significant predictors of the faster progression were
      increasing age and higher CDR stage at entry; however, different types of ChEI
      therapy (donepezil vs. rivastigmine users), and APOE genotype were not associated
      with the rate of disease progression. CONCLUSIONS: This longitudinal data shows
      the mean annual change of the MMSE, CASI, CDR, and CDR-SB in treated AD patients.
      The data may provide clinicians with information regarding to the cognitive
      decline rate in every year while their AD patients receive approved
      pharmacological therapy in real-world practice. Increasing age and severity of
      dementia when receiving therapy are the main factors that associated with faster
      deterioration.

PMID- 29032751
TI  - Development of Drug Targeting and Delivery in Cervical Cancer.
AB  - Cervical cancer is the second most common cancer in women. Standard treatment
      options available for cervical cancer include chemotherapy, surgery and radiation
      therapy associated with their own side effects and toxicities. Tumor-targeted
      delivery of anticancer drugs is perhaps one of the most appropriate strategies to
      achieve optimal outcomes from the treatment and improve the quality of life.
      Recently nanocarriers based drug delivery systems owing to their unique
      properties have been extensively investigated for anticancer drug delivery. In
      addition to that addressing the anatomical significance of cervical cancer,
      various local drug delivery strategies for the cancer treatment are introduced
      like: gels, nanoparticles, polymeric films, rods and wafers, lipid based
      nanocarrier. Localized drug delivery systems allow passive drug targeting results
      in high drug concentration at the target site. Further they can be tailor made to
      achieve both sustained and controlled release behavior, substantially improving
      therapeutic outcomes and minimizing side effects. This review summarizes the
      meaningful advances in drug delivery strategies to treat cervical cancer.

PMID- 29032752
TI  - Association between Apolipoproteins AI and B and Ultrasound Indicators of Carotid
      Atherosclerosis.
AB  - BACKGROUND: Apolipoproteins A-I and B (apoA-I and apoB) may be better indicators
      of the risk of cardiovascular and cerebrovascular diseases than conventional risk
      factors (RFs). The onset of ischemic stroke (IS) may be preceded by the
      development of atherosclerotic changes in carotid arteries, which can be detected
      by ultrasound. Only a certain % of patients with IS have an (underlying) carotid
      etiology. OBJECTIVE: The aim of our study was to determine the association
      between ultrasound indicators of carotid atherosclerosis and the presence of
      apolipoproteins and other biomarkers in patients with IS. METHODS: The study
      included 120 patients with clinically first, non-cardioembolic ischemic stroke in
      the carotid circulation. For all patients the following data were recorded: risk
      factors (hypertension, diabetes, hyperlipoproteinemia, smoking, obesity,
      metabolic syndrome, (MetS) hyperhomocysteinemia and inflammation), and levels of
      blood pressure, glucose, glycosylated hemoglobin, lipids, apoA-I and apoB
      apolipoproteins, body mass index, homocysteine, and C-reactive protein (CRP).
      Carotid duplex ultrasound was used to measure carotid intima media thickness
      (cIMT) and determine the presence of an unstable (hypoechogenic) plaque. RESULTS:
      The most significant associations were found between cIMT and older age
      (beta=0.230; p=0.006), lower concentrations of apoA-I (beta=-0.244; p=0.008) and
      a higher apoB/apoA-I ratio (beta=0.247; p=0.007). The presence of a hypoechogenic
      plaque was most significantly associated with increased concentrations of apoB
      (OR=2.29; 95% CI=4.9-173.5; p<0.0001), the presence of MetS (OR=9.2; 95% CI=2.9
      29.2; p<0.0001) and elevated CRP (OR=2.7; 95% CI=1.1-6.9; p = 0.046). CONCLUSION:
      Among RFs and their biomarkers, apoA-I, apoB and the apoB/apoA-I ratio showed
      strong association with ultrasound indicators of carotid atherosclerosis in IS
      patients.

PMID- 29032753
TI  - Halogenated Agents and Cardiovascular Surgery: Has Mortality Really Decreased?
AB  - Halogenated anesthetic agents (desflurane, isoflurane and sevoflurane) may have
      cardioprotective properties at therapeutic doses against myocardial
      intraoperative ischemia-reperfusion injury. Cardioprotection mechanisms are
      related to mitochondrial and anti-apoptotic signaling pathways. Experimentals and
      human studies have proven that their use may reduce morbidity and mortality in
      the setting of cardiac surgery, including a reduction in myocardial infarct size
      and mechanical ventilation needs. In contrast, total intra-venous propofol based
      anesthesia may be detrimental. In the present review, we show the rationale for
      the perioperative use of halogenated anesthetics based on mechanisms of action,
      experimental research and human studies. Considerations and major concerns
      regarding their use, the present evidence for their use in other areas, such as
      major non-cardiac surgery and intensive care unit patients, and future
      perspectives are also discussed.

PMID- 29032754
TI  - Pharmacological Neuroprotection in Cardiac Surgery: Effectiveness of
      Pharmacologic-Preconditioning with Erythromycin.
AB  - Regardless of the degree of advances in neuroprotective strategies, and despite
      the technological progress in neuromonitoring, brain injury still remains the
      "Achilles' heel" in cardiac surgery. A large number of pharmacological and non
      pharmacological therapeutic interventions have been investigated during the last
      two decades. Recently, both theoretical and experimental findings suggest
      benefits of pharmacological cerebral protection, although, there is no conclusive
      evidence of clinical superiority of specific agents that have been applied as
      neuroprotectants, in human randomized controlled trials. Pre-ischemic
      conditioning has also been used in an attempt to reduce the incidence of brain
      injury following cardiac surgery. In light of previous evidence showing that
      pharmacologic preconditioning with a single dose of erythromycin induces
      tolerance against transient global cerebral ischemia in rats, we examined whether
      erythromycin would reduce the number of apoptotic neurons in the neocortex in our
      acute porcine model of hypothermic circulatory arrest (HCA). Pre-ischemic
      conditioning with a single dose of the antibiotic erythromycin, applied 12 h
      before HCA, significantly reduced neuronal injury in the neocortex of the porcine
      brain, suggesting that cerebral protection may be achieved with erythromycin
      pharmacological preconditioning in cardiac surgery on an experimental basis.
      Since erythromycin has been effectively used in clinical practice with few side
      effects, these findings suggest that it could be a promising candidate for
      potential clinical neuroprotective strategy.

PMID- 29032755
TI  - Insulin Resistance the Link between T2DM and CVD: Basic Mechanisms and Clinical
      Implications.
AB  - Insulin resistance (IR) is a cardinal feature of type 2 diabetes mellitus (T2DM).
      It also is associated with multiple metabolic abnormalities which are known
      cardiovascular disease (CVD) risk factors. Thus, IR not only contributes to the
      development of hyperglycemia in T2DM patients, but also to the elevated CVD risk.
      Improving insulin sensitivity is anticipated to both lower the plasma glucose
      concentration and decrease CVD risk in T2DM patients, independent of glucose
      control. We review the molecular mechanisms and metabolic consequences of IR in
      T2DM patients and discuss the importance of addressing IR in the management of
      T2DM.

PMID- 29032756
TI  - Antidiabetic Drugs as Antihypertensives: New Data on the Horizon.
AB  - BACKGROUND: The prevalence of Type 2 Diabetes Mellitus (T2DM) is increasing
      worldwide; this is stimulating more research into the optimal management of this
      disease. Cardiovascular Disease (CVD) remains the commonest cause of death in
      individuals with T2DM. Besides hyperglycaemia, an explanation for the increased
      mortality in this population is the increased prevalence of comorbidities, such
      as hypertension and dyslipidaemia. Recent population-based studies described a
      prevalence of hypertension >80% in patients with T2DM. In the last decade new
      classes of antidiabetic medications have been developed that are effective not
      only for the management of hyperglycaemia and but also for tailoring treatment
      according to individual needs and characteristics. Regulatory authorities demand
      the new antidiabetic medications to be examined for Cardiovascular (CV) safety.
      Interestingly it has been shown, mainly through CV safety trials, that some new
      antidiabetic medications not only have glucose lowering effects, but also Blood
      Pressure (BP) lowering effects, contributing to CV risk reduction. CONCLUSION:
      This review considers the effect of older and newer antidiabetic medications on
      BP in patients with T2DM.

PMID- 29032757
TI  - An Evidence-based Review of Medicinal Herbs for the Treatment of Gastroesophageal
      Reflux Disease (GERD).
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common
      diseases in society, affecting up to 40% of the population. It has major impact
      on the quality of life and a high burden on medical expenditure. In this work,
      herbs used by ancient Iranians to treat GERD have been introduced. METHODS:
      Different well-known Persian textbooks and recent electronic databases were
      searched to explore the treatment of GERD and the pharmacological mechanisms of
      the identified medicinal plants. RESULTS: GERD has been known for many centuries,
      and many herbal remedies for its treatment have been elucidated in traditional
      medical literature. We found 25 medicinal herbs in Persian medicine books and
      searched for evidence to support them in the current literature. CONCLUSION:
      Although their active components or the mechanism of action were not known by the
      ancient Persians at that time, their persistent use during different centuries
      might indicate their effectiveness. Owing to their potential, medicinal herbs are
      a viable option for the treatment of diseases like GERD even today.

PMID- 29032758
TI  - Multifaceted Effects of Delta Opioid Receptors and DADLE in Diseases of the
      Nervous System.
AB  - BACKGROUND: The opioid system is considered a potential therapeutic target in a
      variety of neurological disorders. Delta opioid receptors (DORs) are broadly
      expressed in the brain, and their activation protects cells from hypoxic/ischemic
      insults by counteracting disruptions of ionic homeostasis and initiating
      neuroprotective pathways. The DOR agonist D-Ala2-D-Leu2-Enkephalin (DADLE)
      promotes neuronal survival, mitigates apoptotic pathways, and protects neurons
      and glial cells from ischemia-induced cell death, thus making DADLE a promising
      therapeutic option for stroke. The significant amount of research regarding DORs
      and DADLE in the last decades also suggests their potential in treating other
      neurological disorders. METHODS: This review compiled relevant literature
      detailing the role of DORs and agonists in central nervous system function and
      neuropathologies. RESULTS: Several studies demonstrate potential mechanisms
      implicating a key interaction between DORs and DADLE in conferring
      neuroprotective benefits. A better understanding of DOR function in disease
      specific contexts is critical to transitioning DOR agonists into the clinic as a
      therapy for stroke and other neurological diseases. CONCLUSION: Evidence-based
      studies support the potential of the delta-opioid family of receptors and its
      ligands in developing novel therapeutic strategies for stroke and other brain
      disorders.

PMID- 29032759
TI  - Predictable and Preventable: Historical and Current Efforts to Improve Child
      Injury Prevention.
AB  - BACKGROUND: Childhood injuries are a global epidemic. Accidents resulting in
      childhood injury and death were first identified as a concern over a century ago.
      However, "accidents" leading to injury were not recognized as being predictable
      and preventable until more recently. OBJECTIVES: To describe the worldwide
      epidemic of childhood injuries, and look at international successes in the field
      of injury prevention. METHODS: Literature pertaining to injury prevention was
      reviewed to describe the history of childhood injury prevention, guiding
      principles of injury prevention, successful strategies for prevention, and future
      directions. RESULT AND CONCLUSION: Through surveillance, evidence-based injury
      prevention initiatives, and multi-disciplinary collaboration, we anticipate
      further reduction in childhood injuries.

PMID- 29032760
TI  - 9-(4'-dimethylaminophenyl)-2,6,7-trihydroxy-xanthene-3-one is a Potentially Novel
      Antiplatelet Drug which Antagonizes the Effect of Thromboxane A2.
AB  - BACKGROUND: Currently, used oral antiplatelet drugs are both limited and
      associated with the risk of treatment failure/resistance. Research in this area
      is hence highly desired. A series of xanthene-3-ones derivatives, we had
      synthesized, showed us that these derivatives had antiplatelet activity. As far
      as we know, no research on the effects of xanthen-3-ones in this area has been
      done. OBJECTIVE: The aim was to study the antiplatelet potential of a series of
      synthesised 9-phenylxanthene- 3-ones and to find the ideal structural feature(s)
      for antiplatelet potential and determine the mechanism of action. METHODS: The
      compounds were synthesized from 1,2,4-triacetoxybenzene and various
      benzaldehydes. The reaction proceeded smoothly under acidic alcoholic conditions,
      furnishing the desired products in good yields. The compounds were first screened
      in whole human blood where platelet aggregation was induced by arachidonic acid.
      Further analysis was targeted at search of the mechanism of action. RESULTS:
      Initial screening showed that a majority of the synthesized derivatives had
      substantial antiplatelet potential. None of the compounds were able to block
      cyclooxygenase 1 or thromboxane synthase. The mechanism appeared to be based on
      antagonism of thromboxane effects. The most potent compound 9-(4'
      dimethylaminophenyl)-2,6,7-trihydroxy-xanthene-3-one had better potential to
      block collagen induced platelet aggregation than clinically used acetylsalicylic
      acid. CONCLUSION: The last mentioned derivative is promising for further in vivo
      testing.

PMID- 29032761
TI  - Investigation on the Effects of Antimicrobial imidazo[2,1-b]thiazole Derivatives
      on the Genitourinary Microflora.
AB  - BACKGROUND: Fused five-membered heterocyclic rings containing bridgehead nitrogen
      atom are particularly versatile in the field of medicinal chemistry because of
      their different biological activities. Among them, the imidazo[2,1-b]thiazole is
      an attractive fused heterocyclic core that has been extensively studied.
      OBJECTIVE: The aim of the current study was to study the therapeutic applications
      of imidazo[2,1- b]thiazole derivatives as antimicrobial agents for the treatment
      of genitourinary infections. METHOD: A traditional synthetic methodology was
      involved to obtain a small series of imidazothiazole derivatives. RESULTS:
      Herein, we report the antimicrobial activity of the imidazo[2,1-b]thiazole or
      imidazo[2,1- b]thiazolidine derivatives against selected fungi, Gram-positive and
      Gram-negative bacteria. Moreover, experiments were carried out to investigate the
      interference towards the endogenous microbiota. CONCLUSION: The most interesting
      of the series are the thiocyano derivatives (19, 23) showing a good profile for
      the treatment of genitourinary infections: a spectrum of activity covering both
      bacteria and fungi together with a reduced impact versus critical lines of
      Lactobacillus exerting defense against pathogens.

PMID- 29032762
TI  - A Review of Evolutionary and Cyclical Changes in the Surgical Approach to Aortic
      Valve Disease.
AB  - INTRODUCTION: Aortic valve surgery is no exception to the general rule that
      history is a cycle in many fields. This manuscript aims to assist readers in
      transitioning from past to present and on into the future within the field of
      aortic valve surgery. METHODS: The existing literature has been examined,
      including old and modern articles published on pubmed, old articles non visible
      on pubmed, old and recent books on the history of medicine, looking for
      similarities and repetitions in techniques and surgical approaches to the aortic
      valve in the past and the current times. RESULTS: Steps of evolution included a
      blind approach, plasty procedures under direct visualization of the valve without
      the aid of cardiopulmonary bypass, prosthetic valve replacements via sternotomies
      with cardiopulmonary bypass, minimally-invasive access routes, trans-catheter
      aortic valve implants (TAVI), suture-less prostheses, mini-thoracotomies
      incorporating suture-less prostheses, and finally, totally-endoscopic aortic
      valve replacements. CONCLUSION: After the advent of CPB and several decades of
      open-heart surgery with full sternotomies, the minimally-invasive approach has re
      emerged. Supported by a commitment to smaller incisions and shorter bypass times,
      the concept is now being aggressively developed. The cycling of science,
      including the field of aortic valve surgery, means that ingenious theories and
      concepts that have fallen by the wayside can be brought back and explored again
      with current tools and enhanced knowledge.

PMID- 29032763
TI  - Basics in Endoscopic Ultrasound Part 1: Diagnostic Indications and Tissue
      Sampling.
AB  - BACKGROUND: Endoscopic Ultrasound has been used in the clinical arena for almost
      35 years and it is now well-integrated in everyday hospital practice. METHOD: We
      conducted a systematic review of the available English-language articles.
      OBJECTIVE: The purpose of this review is to summarize all the relevant
      indications to endoscopic ultrasound and analyze its relevant data in terms of
      accuracy and clinical outcomes. RESULTS: More than 5000 scientific papers
      published in the literature have demonstrated its high accuracy for the diagnosis
      and staging of a variety of benign and malignant conditions. Staging indications
      include gastroesophageal and rectal cancers. Diagnostic, staging and therapeutic
      indications include diseases of the pancreaticobiliary area. Finally,
      differential diagnosis of submucosal tumors represents another important
      indication to this technique.

PMID- 29032764
TI  - Nanoemulsions for Cosmetic Applications: What Innovation Status?
AB  - BACKGROUND: Brazil is the fourth largest personal hygiene, perfumery and
      cosmetics (HPPC) consumer market in the world, leading industries to invest
      heavily in cosmetic research. Nanotechnology is studied and applied in several
      branches of health and, in the cosmetic area, focuses on the effectiveness of the
      products, safety of use and stability of the formulation. Thus, nanoemulsions
      appear as an attractive option for cosmetic manufacturers. OBJECTIVE: In this
      context, a technological investigation was carried out, through a patent search,
      with the objective of verifying the current panorama of the nanoemulsions for the
      development of cosmetic formulations. METHOD: To do this, we consulted the
      Espacenet(r) database, using the word "nanoemulsion", associated with the IPC
      code "A61q19". A total of 188 patents were found, of which 118 were available for
      display, whose data were organized into charts for discussion. RESULT: The
      results show that developed countries are still the largest patent holders in the
      area, with the exception of South Korea, which ranked first with 39 patent
      applications. France appears as the most important in this research, but the
      largest market of interest for this technology is North America. Brazil seems to
      have less number of patents (3) and have not been registered in the country.
      CONCLUSION: The predominance of cosmetic nanoemulsions was mainly for aesthetic
      purposes. Nanoemulsions for cosmetic application still have potential for
      research and development, especially when related to raw materials of plant
      origin, where Brazil can be highlighted.

PMID- 29032765
TI  - Recent Patent Advances for Neurodegenerative Disorders and its Treatment.
AB  - BACKGROUND: Neurodegenerative disorders are among the most common challenging
      diseases that affect the population with extreme medical and financial burdens.
      Widely seen neurodegeneration affects population of all ages, as it progresses
      with age, affecting a large proportion of elderly population including patients,
      caregivers, and immensely increasing the financial load of the country. These
      diseases have a very complex nature that frequently results from combined
      genetic, environmental and pathological factors. Various challenges are faced by
      the researchers working on the pathogenesis and the possible treatment of
      neurodegenerative disorder. OBJECTIVE: The review has analysed for recent patent
      documents and treatment approaches for neurodegenerative disorders. This review
      does not relate to potential targets such as ( i.e. protein where modulation
      could be predicted to impact on pathophysiology), rather it mainly focuses on
      various available patented approaches for neurodegenerative disorders. METHOD:
      The study design is based on updating the international and national literatures
      and an exhaustive patent search, compiling various patented documents for the
      treatment of neurodegenerative disorders (EP2282779A1, US20110229555A1) to
      provide information in the state of technological innovation in terms of research
      and development. RESULTS: In the present review, the authors described various
      neurodegenerative diseases, there treatment strategies and emphasized on various
      patented approaches for age-related neurodegenerative disorders such as novel
      therapeutic methods for treating Alzheimer's and associated disorders via
      modulated cell stress response EP2282779A1, through combined therapies that
      modulate angiogenesis US20120058992A1. CONCLUSION: The review will attract the
      interest of academics, researchers, students and pharmaceutical companies with
      regard to the recent on-going activities in neurodegenerative disorders.

PMID- 29032766
TI  - The Effects of Drug Metabolizing Enzyme Inhibitors on Hepatic Efflux and Uptake
      Transporters.
AB  - BACKGROUND: Non-selective chemical inhibitors of phase I and phase II enzymes are
      commonly used in in vitro metabolic studies to elucidate the biotransformation
      pathways of drugs. However, the inhibition of the inhibitors on efflux and uptake
      transporters is not well investigated, potentially leading to unexpected and
      ambiguous results in these studies. OBJECTIVE: The commonly used metabolizing
      enzyme inhibitors, 1-aminobenzotriazole (ABT), SKF- 525A, pargyline, allopurinol,
      menadione, methimazole, piperine and raloxifene, were examined for their
      potential inhibition of the major hepatic ABC (ATP binding cassette) and SLC
      (solute carrier) transporters. METHODS: Different concentrations of the
      metabolizing enzyme inhibitors were used to study their effects on ABC and SLC
      transporters expressed in MDR1-MDCKI, Bcrp1-MDCKII, OATP1B1-HEK, OATP1B3-HEK,
      OCT1-HEK, OCT3-HEK cells and MRP2 vesicles. RESULTS: ABT, allopurinol and
      methimazole had no inhibitory effects on MDR1, Bcrp1, MRP2 or on OATP1B1,
      OATP1B3, OCT1 or OCT3. Pargyline did not inhibit OATP1B1 or OATP1B3, but weakly
      inhibited OCT1 and OCT3. In contrast, SKF-525A showed inhibition of not only
      MDR1, Bcrp1 and MRP2 but also OATP1B1, OATP1B3 and OCT1. Menadione and raloxifene
      weakly inhibited Bcrp1, but the inhibition of raloxifene on MDR1 was as potent as
      on the xanthine oxidase pterin oxidation. Piperine showed inhibition of MDR1,
      Bcrp1, OATP1B1, OCT1 and OCT3. CONCLUSION: ABT, pargyline, allopurinol and
      methimazole have no inhibitory effects on the studied ABC and SLC transporters,
      suggesting the inhibitors are unlikely to cause confounding inhibition of
      transporters when used in metabolism studies. However, SKF525A, menadione,
      raloxifene and piperine can inhibit the activities of ABC and/or SLC
      transporters.

PMID- 29032768
TI  - Molluscicidal effect of Achyranthes aspera L. (Amaranthaceae) aqueous extract on
      adult snails of Biomphalaria pfeifferi and Lymnaea natalensis.
AB  - BACKGROUND: Intestinal schistosomiasis caused by Schistosoma mansoni is a wide
      spread disease in most parts of Ethiopian highlands. Snail control is one major
      strategy in schistosomiasis control. The use of molluscicidal plant products is
      becoming interesting due to their environmental friendliness, accessibility and
      easy application. This research is aimed to evaluate the molluscicidal effect of
      Achyranthes aspera on Biomphalaria pfeifferi and Lymnaea natalensis snails, which
      are of great medical and veterinary importance in Ethiopia. METHODS: Adult B.
      pfeifferi snails were exposed to the various concentrations of A. aspera aqueous
      leaf extract for 24, 48 and 72 h. Similarly, adult L. natalensis snails were
      exposed to the extract for 24 h. Mortality data were analyzed using probit
      regression model. Phytochemical content of the plant was analyzed using standard
      screening methods. RESULTS: The plant's molluscicidal effect on the two snail
      species was demonstrated. The 24 h LC50 and LC90 values against L. natalensis
      were 69.5 and 93.9 ppm respectively. In the 24, 48 and 72 h exposure of B.
      pfeifferi, the LC50 values were 72.4, 69.9, 64.7 ppm and the LC90 were 96.5,
      93.8, 92.8 ppm, respectively. The phytochemical screening tests indicated
      presence of saponins. CONCLUSION: From the findings of this study, A. aspera has
      a molluscicidal potential. The result provides a useful foundation for further in
      depth studies to ensure its wider applicability in different water bodies and
      evaluate its toxic effects on non-target species.

PMID- 29032767
TI  - Metabonomics uncovers a reversible proatherogenic lipid profile during infliximab
      therapy of inflammatory bowel disease.
AB  - BACKGROUND: One-third of inflammatory bowel disease (IBD) patients show no
      response to infliximab (IFX) induction therapy, and approximately half of
      patients responding become unresponsive over time. Thus, identification of
      potential treatment response biomarkers are of great clinical significance. This
      study employs spectroscopy-based metabolic profiling of serum from patients with
      IBD treated with IFX and healthy subjects (1) to substantiate the use of
      spectroscopy as a semi-invasive diagnostic tool, (2) to identify potential
      biomarkers of treatment response and (3) to characterise the metabolic changes
      during management of patients with tumour necrosis factor-alpha inhibitors.
      METHODS: Successive serum samples collected during IFX induction treatment (weeks
      0, 2, 6 and 14) from 87 IBD patients and 37 controls were analysed by 1H nuclear
      magnetic resonance (NMR) spectroscopy. Data were analysed with principal
      components analysis and orthogonal projection to latent structures discriminant
      analysis using SIMCA-P+ v12 and MATLAB. RESULTS: Metabolic profiles were
      significantly different between active ulcerative colitis and controls, active
      Crohn's disease and controls, and quiescent Crohn's disease and controls.
      Metabolites holding differential power belonged primarily to lipids and
      phospholipids with proatherogenic characteristics and metabolites in the pyruvate
      metabolism, suggestive of an intense inflammation-driven energy demand. IBD
      patients not responding to IFX were identified as a potentially distinct group
      based on their metabolic profile, although no applicable response biomarkers
      could be singled out in the current setting. CONCLUSION: 1H NMR spectroscopy of
      serum samples is a powerful semi-invasive diagnostic tool in flaring IBD. With
      its use, we provide unique insights into the metabolic changes taking place
      during induction treatment with IFX. Of distinct clinical relevance is the
      identification of a reversible proatherogenic lipid profile in IBD patients with
      active disease, which partially explains the increased risk of cardiovascular
      disease associated with IBD.

PMID- 29032770
TI  - Developmental competence of Dromedary camel (Camelus dromedarius) oocytes
      selected using brilliant cresyl blue staining - ERRATUM.

PMID- 29032769
TI  - Amphetamine Modestly Improves Conners' Continuous Performance Test Performance in
      Healthy Adults.
AB  - OBJECTIVES: Amphetamine improves vigilance as assessed by continuous performance
      tests (CPT) in children and adults with attention deficit hyperactivity disorder
      (ADHD). Less is known, however, regarding amphetamine effects on vigilance in
      healthy adults. Thus, it remains unclear whether amphetamine produces general
      enhancement of vigilance or if these effects are constrained to the remediation
      of deficits in patients with ADHD. METHODS: We tested 69 healthy adults (35
      female) on a standardized CPT (Conner's CPT-2) after receiving 10- or 20-mg d
      amphetamine or placebo. To evaluate potential effects on learning, impulsivity,
      and perseveration, participants were additionally tested on the Iowa Gambling
      Task (IGT) and Wisconsin Card Sorting Task (WCST). RESULTS: Participants
      receiving placebo exhibited the classic vigilance decrement, demonstrated by a
      significant reduction in attention (D') across the task. This vigilance decrement
      was not observed, however, after either dose of amphetamine. Consistent with
      enhanced vigilance, the 20-mg dose also reduced reaction time variability across
      the task and the ADHD confidence index. The effects of amphetamine appeared to be
      selective to vigilance since no effects were observed on the IGT, WCST, or
      response inhibition/perseveration measures from the CPT. CONCLUSIONS: The present
      data support the premise that amphetamine improves vigilance irrespective of
      disease state. Given that amphetamine is a norepinephrine/dopamine transporter
      inhibitor and releaser, these effects are informative regarding the
      neurobiological substrates of attentional control. (JINS, 2018, 24, 283-293).

PMID- 29032771
TI  - Short-term effects of atmospheric pressure, temperature, and rainfall on
      notification rate of community-acquired Legionnaires' disease in four European
      countries - CORRIGENDUM.

PMID- 29032772
TI  - Influenza vaccination status and outcomes among influenza-associated
      hospitalizations in Columbus, Ohio (2012-2015).
AB  - Prior studies suggest that the influenza vaccine is protective against some
      outcomes in hospitalized patients infected with influenza despite vaccination. We
      utilized surveillance data from Columbus, Ohio to investigate this association
      over multiple influenza seasons and age groups. Data on laboratory-confirmed
      influenza-associated hospitalizations were collected as a part of the Influenza
      Hospitalization Surveillance Project for the 2012-2013, 2013-2014, and 2014-2015
      influenza seasons. The association between influenza vaccination status was
      examined in relation to the outcomes of severe influenza and diagnosis of
      pneumonia among patients receiving antiviral treatment. Data were analyzed using
      multivariable logistic regression. We observed no overall association between
      influenza vaccination status and severe influenza among hospitalized patients.
      During the 2013-2014 season, those who were vaccinated were 41% less likely to be
      diagnosed with pneumonia compared with those who were unvaccinated (OR = 0.59 95%
      CI 0.41-0.86). The influenza vaccine may provide a secondary preventive function
      against pneumonia among influenza cases requiring hospitalization. However, a
      protective effect was only observed in 2013-2014, an influenza H1N1 dominant
      year. Differences in circulating influenza virus strains and vaccine matching to
      the circulating strains during influenza seasons may impact this association.

PMID- 29032773
TI  - Understanding the development of psychopathy: progress and challenges.
AB  - Psychopathy is an adult condition that incurs substantial societal and individual
      costs. Here we review neurocognitive and genetically informative studies that
      shed light on how and why this condition emerges. Children cannot present with
      psychopathy. However, the presence of callous-unemotional (CU) traits can
      distinguish a group of children who are at elevated risk of psychopathy in
      adulthood. These children display diminished empathy and guilt and show
      attenuated brain activation to distress cues in others. Genetically informative
      studies indicate that individual differences in CU traits show moderate-to-strong
      heritability, but that protective environmental factors can counter heritable
      risk. On the basis of the extant research findings, we speculate on what might
      represent the priorities for research over the next decade. We also consider the
      clinical implications of these research findings. In particular, we consider the
      importance of delineating what precisely works for children with CU traits (and
      their parents) and the ways in which intervention and prevention programs may be
      optimized to improve engagement as well as clinical outcomes.

PMID- 29032774
TI  - The potential roles of c-Jun N-terminal kinase (JNK) during the maturation and
      aging of oocytes produced by a marine protostome worm.
AB  - Previous investigations have indicated that c-Jun N-terminal kinase (JNK)
      regulates the maturation and aging of oocytes produced by deuterostome animals.
      In order to assess the roles of this kinase in a protostome, oocytes of the
      marine nemertean worm Cerebratulus were stimulated to mature and subsequently
      aged before being probed with phospho-specific antibodies against active forms of
      JNK and maturation-promoting factor (MPF). Based on blots of maturing oocytes, a
      40-kD putative JNK is normally activated during germinal vesicle breakdown
      (GVBD), which begins at 30 min post-stimulation with seawater, whereas treating
      immature oocytes with JNK inhibitors downregulates both the 40-kD JNK signal and
      GVBD, collectively suggesting a 40-kD JNK may facilitate oocyte maturation. Along
      with this JNK activity, mature oocytes also exhibit high levels of MPF at 2 h
      post-stimulation. However, by ~6-8 h post-GVBD, mature oocytes lose the 40-kD JNK
      signal, and at ~20-30 h of aging, an ~48-kD phospho-JNK band arises as oocytes
      deactivate MPF and begin to lyse during a necroptotic-like mode of death.
      Accordingly, JNK inhibitors reduce the aging-related 48-kD JNK phosphorylation
      while maintaining MPF activity and retarding oocyte degradation. Such findings
      suggest that a 48-kD JNK may help deactivate MPF and trigger death. Possible
      mechanisms by which JNK activation either together with, or independently of,
      protein neosynthesis might stimulate oocyte degradation are discussed.

PMID- 29032775
TI  - Noncommunicable Diseases After the Great East Japan Earthquake: Systematic
      Review, 2011-2016.
AB  - OBJECTIVE: Noncommunicable diseases (NCDs), including mental disorders, have
      become major threats to human health worldwide. People with NCDs are particularly
      vulnerable to disasters. We systematically reviewed reports describing studies of
      NCDs at the time of the Great East Japan Earthquake (GEJE) to clarify the
      circumstances of people with NCDs and to build strong measures to support them.
      METHODS: Relevant articles published from March 2011 through December 2016 were
      collected by searching the PubMed database (National Library of Medicine). We
      specifically examined reports describing NCDs and including the key words "East
      Japan Earthquake." NCDs included every disease type aside from injury and
      infectious disease. RESULTS: We collected 160 relevant articles, 41 of which
      described NCDs that existed in residents before the GEJE. Articles describing
      respiratory diseases and mental illnesses were found most frequently.
      Interruption of regular treatment was the most frequent problem, followed by lack
      of surveillance capacity. We found 101 reports describing NCDs that had developed
      after the GEJE, of which 60% were related to mental health issues. CONCLUSIONS:
      NCDs pose major health issues after large-scale disasters. Establishment of
      strong countermeasures against interruption of treatment and surveillance systems
      to ascertain medical needs for NCDs are necessary to prepare for future
      disasters. (Disaster Med Public Health Preparedness. 2018; 12: 396-407).

PMID- 29032777
TI  - Acute urinary retention after Black Widow envenomation: a case report.
AB  - Latrodectism following Black Widow envenomation is rare in Canada. We present the
      case of a previously healthy 50 year old male who presented with an acute
      abdomen, hypertension, and urinary retention. After a thorough work up it was
      determined to be as a result of a Black Widow spider bite. Due to climate change
      we may see more cases of Latrodectism in the future and it should be considered
      as a differential diagnosis in anyone presenting with an acute abdomen after an
      insect bite.

PMID- 29032776
TI  - Neuropsychological Recovery Trajectories in Moderate to Severe Traumatic Brain
      Injury: Influence of Patient Characteristics and Diffuse Axonal Injury.
AB  - OBJECTIVES: The goal of the present study was to elucidate the influence of
      demographic and neuropathological moderators on the longitudinal trajectory
      neuropsychological functions during the first year after moderate to severe
      traumatic brain injury (TBI). In addition to examining demographic moderators
      such as age and education, we included a measure of whole-brain diffuse axonal
      injury (DAI), and examined measures of processing speed (PS), executive function
      (EF), and verbal learning (VL) separately. METHODS: Forty-six adults with
      moderate to severe TBI were examined at 3, 6, and 12 months post-injury.
      Participants underwent neuropsychological evaluation and neuroimaging including
      diffusion tensor imaging. Using linear mixed effects modeling, we examined
      longitudinal trajectories and moderating factors of cognitive outcomes separately
      for three domains: PS, VL, and EF. RESULTS: VL and EF showed linear improvements,
      whereas PS exhibited a curvilinear trend characterized by initial improvements
      that plateaued or declined, depending on age. Age moderated the recovery
      trajectories of EF and PS. Education and DAI did not influence trajectory but
      were related to initial level of functioning for PS and EF in the case of DAI,
      and all three cognitive domains in the case of education. CONCLUSIONS: We found
      disparate recovery trajectories across cognitive domains. Younger age was
      associated with more favorable recovery of EF and PS. These findings have both
      clinical and theoretical implications. Future research with a larger sample
      followed over a longer time period is needed to further elucidate the factors
      that may influence cognitive change over the acute to chronic period after TBI.
      (JINS, 2018, 24, 237-246).

PMID- 29032778
TI  - Has iodized salt reduced iodine-deficiency disorders among school-aged children
      in north-west Iran? A 9-year prospective study.
AB  - OBJECTIVE: Low iodine intakes are associated with goitre and other iodine
      deficiency disorders (IDD) that have affected billions of people worldwide. We
      aimed to assess total goitre rate (TGR) and urinary iodine concentration (UIC) in
      schoolchildren between 2007 and 2015, percentage of iodized salt consumption by
      households, and salt iodine content at production, distribution and household
      levels in north-west Iran. Design/Setting/Subjects UIC assessed among
      schoolchildren in nine consecutive years; 240 schoolchildren aged 8-10 years
      selected by systematic random sampling each year in the West Azerbaijan Province.
      RESULTS: Median UIC was >100 MUg/l in all years. More than 50 % of children had
      iodine deficiency (UIC<=99 MUg/l) in 2010 and 2011, while this rate was
      approximately 15-35 % in other years. Proportion with UIC below 50 MUg/l was <20
      % in all years except 2010 and 2011. Excessive UIC (>=300 MUg/l) rate was between
      5.4 and 27.5 %. TGR decreased from 44 % in 1996 to 7.6 % and 0.4 % in 2001 and
      2007, respectively. Regular surveys from 2002 to 2015 showed that 98 % or more of
      households consumed iodized salt. Iodine level >=20 ppm was observed in 87.5, 83
      and 73 % of salt at production, distribution and household level, respectively
      (data from national study in 2007). The last national study in 2014 showed that
      median iodine level in household salt was 27 ppm. CONCLUSIONS: Our focused data
      suggest that the universal salt iodization programme is improving the iodine
      status of schoolchildren in the West Azerbaijan Province of Iran. Reduction of
      TGR to less than 5 % in schoolchildren indicates successful elimination of IDD as
      a major public health problem.

PMID- 29032779
TI  - Combined effects of oleic, linoleic and linolenic acids on lactation performance
      and the milk fatty acid profile in lactating dairy cows.
AB  - The potential combined effects of oleic, linoleic and linolenic acids
      supplementation on lactation performance and the milk fatty acid (FA) profile in
      dairy cows have not been well investigated. Our objective was to examine the
      effects of supplementation with a combination of these FA as well as the effects
      of removing each from the combination on lactation performance and the milk FA
      profile in dairy cows. Eight Holstein cows (101+/-11 days in milk) received four
      intravenously infused treatments in a 4*4 Latin square design, and each period
      lasted for 12 days which consisted of 5 days of infusion and 7 days of recovery.
      The control treatment (CTL) contained 58.30, 58.17 and 39.96 g/day of C18 : 1 cis
      9; C18 : 2 cis-9, cis-12; and C18 : 3 cis-9, cis-12, cis-15, respectively. The
      other three treatments were designated --C18 : 1 (20.68, 61.17 and 41.72 g/day of
      C18 : 1 cis-9; C18 : 2 cis-9, cis-12; and C18 : 3 cis-9, cis-12, cis-15,
      respectively), -C18 : 2 (61.49, 19.55 and 42.13 g/day of C18 : 1 cis-9; C18 : 2
      cis-9, cis-12; and C18 : 3 cis-9, cis-12, cis-15, respectively) and -C18 : 3
      (60.89, 60.16 and 1.53 g/day of C18 : 1 cis-9; C18 : 2 cis-9, cis-12; and C18 : 3
      cis-9, cis-12, cis-15, respectively). Dry matter intake and lactose content were
      not affected by the treatments, but the milk protein content was lower in cows
      treated with -C18 : 2 than that in CTL-treated cows. Milk yield as well as milk
      fat, protein and lactose yields were higher in cows treated with -C18 : 3 than
      the yields in CTL-treated cows, and these yields increased linearly as the
      unsaturation degree of the supplemental FA decreased. Compared with the CTL
      treatment, the -C18 : 2 treatment decreased milk C18 : 2 cis-9 content (by 2.80%)
      and yield (by 22.12 g/day), and the -C18 : 3 treatment decreased milk C18 : 3 cis
      9, cis-12, cis-15 content (by 2.72%) and yield (by 22.33 g/day). In contrast,
      removing C18 : 1 cis-9 did not affect the milk content or yield of C18 : 1 cis-9.
      The -C18 : 2-treated cows had a higher C18 : 1 cis-9 content and tended to have a
      higher C18 : 1 cis-9 yield than CTL-treated cows. The yields of C8 : 0, C14 : 0
      and C16 : 0 as well as <C16 : 0 tended to increase linearly as the unsaturation
      degree of the supplemental FA decreased (P=0.06, 0.07, 0.07 and 0.09,
      respectively). These results indicated that supplementation with C18 unsaturated
      FA might not independently affect the lactation performance and the milk FA
      profile of dairy cows.

PMID- 29032780
TI  - Prediction of the amino acid digestibility of legume seeds in growing pigs: a
      meta-analysis approach.
AB  - On pig farms, a high proportion of the cost of production comes from feed costs.
      However, the use of alternative ingredients such as legume seeds may help to
      reduce this cost. In fact, legume seeds are an important source of essential
      amino acids (EAA) and can therefore be an alternative to oilseed meals. However,
      the accurate use of these legume seeds requires a precise knowledge of the
      standardized ileal digestibility (SID) of EAA, which may vary depending on its
      botanical variety. A meta-analysis was performed on a database compiling data
      from 41 studies published between 1981 and 2013 and 178 dietary treatments.
      Models of prediction of the SID of EAA as well as the dietary concentration of
      digestible standardized EAA (dEAA) were obtained, based on the chemical
      composition of ingredients reported in the publications. The effect of the type
      of legume seeds (faba bean, lupin, pea and soya bean), surgical procedures (T
      cannula, re-entrant cannulas, post valve T-cannulas and ileo-rectal anastomosis),
      and BW of pigs (BW?25 kg BW>25 kg) were also tested in each model. Results showed
      that dietary CP and crude fibre (CF) were, respectively, the best predictors of
      each EAA SID for faba bean, lupin and pea (R 2=0.42 to 0.89) and soya bean (R
      2=0.32 to 0.77). For the dEAA content, the best prediction models included
      dietary CP and ADF for faba bean, lupin and pea and soya bean, respectively, with
      R 2 ranging from 0.66 to 0.98. Models developed in this study allow predicting
      the digestibility of EAA in these alternatives feedstuffs.

PMID- 29032781
TI  - Bayesian single-step genomic evaluations combining local and foreign information
      in Walloon Holsteins.
AB  - Most dairy cattle populations found in different countries around the world are
      small to medium sized and use many artificial insemination bulls imported from
      different foreign countries. The Walloon population in the southern part of
      Belgium is a good example for such a small-scale population. Wallonia has also a
      very active community of Holstein breeders requesting high level genetic
      evaluation services. Single-step Genomic BLUP (ssGBLUP) methods allow the
      simultaneous use of genomic, pedigree and phenotypic information and could reduce
      potential biases in the estimation of genomically enhanced breeding values
      (GEBV). Therefore, in the context of implementing a Walloon genomic evaluation
      system for Holsteins, it was considered as the best option. However, in contrast
      to multi-step genomic predictions, natively ssGBLUP will only use local
      phenotypic information and is unable to use directly important other sources of
      information coming from abroad, for example Multiple Across Country Evaluation
      (MACE) results as provided by the Interbull Center (Uppsala, Sweden). Therefore,
      we developed and implemented single-step Genomic Bayesian Prediction (ssGBayes),
      as an alternative method for the Walloon genomic evaluations. The ssGBayes method
      approximated the correct system of equations directly using estimated breeding
      values (EBV) and associated reliabilities (REL) without any explicit deregression
      step. In the Walloon genomic evaluation, local information refers to Walloon EBV
      and REL and foreign information refers to MACE EBV and associated REL. Combining
      simultaneously all available genotypes, pedigree, local and foreign information
      in an evaluation can be achieved but adding contributions to left-hand and right
      hand sides subtracting double-counted contributions. Correct propagation of
      external information avoiding double counting of contributions due to
      relationships and due to records can be achieved. This ssGBayes method computed
      more accurate predictions for all types of animals. For example, for genotyped
      animals with low Walloon REL (<0.25) without MACE results but sired by genotyped
      bulls with MACE results, the average increase of REL for the studied traits was
      0.38 points of which 0.08 points could be traced to the inclusion of MACE
      information. For other categories of genotyped animals, the contribution by MACE
      information was also high. The Walloon genomic evaluation system passed for the
      first time the Interbull GEBV tests for several traits in July 2013. Recent
      experiences reported here refer to its use in April 2016 for the routine genomic
      evaluations of milk production, udder health and type traits. Results showed that
      the proposed methodology should also be of interest for other, similar,
      populations.

PMID- 29032782
TI  - Pelleting and extrusion can ameliorate negative effects of toasting of rapeseed
      meal on protein digestibility in growing pigs.
AB  - Toasting time (TT) of rapeseed meal (RSM), the diet processing (DP) method and
      the interaction between both on the apparent CP digestion along the
      gastrointestinal tract and the apparent ileal digestibility (AID) of amino acids
      of growing pigs were investigated. The experiment consisted of a 3*3 factorial
      design of TT of RSM (0, 60 and 120 min) and DP method (mash, pelleting and
      extrusion). In total, 81 boars with a starting BW of 20 kg were euthanized 4 h
      after their last feeding. The gastrointestinal tract was dissected and the small
      intestine divided in three sections of similar length. Samples were collected
      from the stomach, 1.5 m from the ends of each of the three sections of the small
      intestine, and the rectum. The apparent digestibility (AD) of CP for each of the
      small intestine sections was used to calculate the rate of CP digestion.
      Increasing the TT of RSM resulted in lower protein solubility, lower
      lysine/reactive lysine contents and higher protein denaturation, indicative of
      the occurrence of protein aggregation and Maillard reactions. There were
      significant effects (P?0.01) of TT on the AD of CP in the different sections of
      the gastrointestinal tract. The rate of CP digestion of the 0 min toasted RSM
      diets was 23% and 35% higher than that of the 60 and 120 min toasted RSM diets,
      respectively. There was a significant interaction (P=0.04) between TT and DP for
      the AID of CP. Although pelleting of the 0 and 60 min toasted RSM diets did not
      change the AID of CP with respect to the mash diets, pelleting of the 120 min
      toasted RSM diet increased the AID of CP by 9.3% units. Extrusion increased the
      AID of CP of the 0 and 60 min toasted RSM diets by 3.4% and 4.3% units with
      respect to the mash diets, whereas extrusion of the 120 min toasted RSM diet
      increased the AID of CP by 6.9% units. Similar positive effects of pelleting and
      extrusion were obtained for the AID of lysine and reactive lysine, especially in
      the diets with higher TT. In conclusion, processing (pelleting and extrusion) of
      RSM containing diets can ameliorate the negative effects of RSM toasting on
      protein and amino acid digestibility; these effects were larger for the RSM
      toasted for longer times.

PMID- 29032783
TI  - Targeted metabolomics: new insights into pathobiology of retained placenta in
      dairy cows and potential risk biomarkers.
AB  - A targeted quantitative metabolomics approach was used to study temporal changes
      of serum metabolites in cows that normally released their fetal membranes and
      those that retained the placenta. We identified and measured serum concentrations
      of 128 metabolites including amino acids, acylcarnitines, biogenic amines,
      glycerophospholipids, sphingolipids and hexose at -8 and -4 weeks before
      parturition, during the week of retained placenta (RP) diagnosis, and at +4 and
      +8 weeks after parturition. In addition, we aimed at identifying metabolite
      signatures of pre-RP in the serum that might be used as predictive biomarkers for
      risk of developing RP in dairy cows. Results revealed major alterations in the
      metabolite fingerprints of pre-RP cows starting as early as -8 weeks before
      parturition and continuing as far as +8 weeks after calving. Biomarker candidates
      found in this study are mainly biomarkers of inflammation which might not be
      specific to RP. Therefore, the relevance of serum Lys, Orn, acetylornithine,
      lysophophatidylcholine LysoPC a C28:0, Asp, Leu and Ile as potential serum
      biomarkers for prediction of risk of RP in dairy cows will have to be tested in
      the future. In addition, lower concentrations of LysoPCs, Trp, and higher
      kynurenine in the serum during prepartum and the week of occurrence of RP suggest
      involvement of inflammation in the pathobiology of RP.

PMID- 29032784
TI  - Spent culture medium analysis from individually cultured bovine embryos
      demonstrates metabolomic differences.
AB  - Spent culture medium can provide valuable information regarding the physiological
      state of a bovine preimplantation embryos through non-invasive analysis of the
      sum/depleted metabolite constituents. Metabolomics has become of great interest
      as an adjunct technique to morphological and cleavage-rate assessment, but more
      importantly, in improving our understanding of metabolism. In this study, in
      vitro produced bovine embryos developing at different rates were evaluated using
      proton nuclear magnetic resonance (1H NMR). Spent culture medium from
      individually cultured embryos (2-cell to blastocyst stage) were divided into two
      groups based on their cleavage rate fast growing (FG) and slow growing (SG;
      developmentally delayed by 12-24 h), then analyzed by a 600 MHz NMR spectrometer.
      Sixteen metabolites were detected and investigated for sum/depletion throughout
      development. Data indicate distinct differences between the 4-cell SG and FG
      embryos for pyruvate (P < 0.05, n = 9) and at the 16-cell stage for acetate,
      tryptophan, leucine/isoleucine, valine and histidine. Overall sum/depletion
      levels of metabolites demonstrated that embryos produced glutamate, but consumed
      histidine, tyrosine, glycine, methionine, tryptophan, phenylalanine, lysine,
      arginine, acetate, threonine, alanine, pyruvate, valine, isoleucine/leucine, and
      lactate with an overall trend of higher consumption of these metabolites by FG
      groups. Principal component analysis revealed distinct clustering of the plain
      medium, SG, and FG group, signifying the uniqueness of the metabolomic signatures
      of each of these groups. This study is the first of its kind to characterize the
      metabolomic profiles of SG and FG bovine embryos produced in vitro using 1H NMR.
      Elucidating differences between embryos of varying developmental rates could
      contribute to a better understanding of embryonic health and physiology.

PMID- 29032785
TI  - Two glutathione transferase isoforms isolated from juvenile cysts of Taenia
      crassiceps: identification, purification and characterization.
AB  - We identified and characterized the first two glutathione transferases (GSTs)
      isolated from juvenile cysts of Taenia crassiceps (EC 2.5.1.18). The two
      glutathione transferases (TcGST1 and TcGST2) were purified in a single-step
      protocol using glutathione (GSH)-sepharose chromatography in combination with a
      GSH gradient. The specific activities of TcGST1 and TcGST2 were 26 U mg-1 and 19
      U mg-1, respectively, both at 25 degrees C and pH 6.5 with 1-chloro-2,4
      dinitrobenzene (CDNB) and GSH as substrates. The Km(CDNB) and Kcat(CDNB) values
      for TcGST1 and TcGST2 (0.86 MUm and 62 s-1; 1.03 MUm and 1.97 s-1, respectively)
      and Km(GSH) and Kcat(GSH) values for TcGST1 and TcGST2 (0.55 MUm and 11.61 s-1;
      0.3 MUm and 32.3 s-1, respectively) were similar to those reported for mammalian
      and helminth GSTs. Mass spectrometry analysis showed that eight peptides from
      each of the two parasite transferases were a match for gi|29825896 glutathione
      transferase (Taenia solium), confirming that both enzymes are GSTs. The relative
      molecular masses were 54,000 +/- 0.9 for the native enzymes and 27,500 +/- 0.5
      for the enzyme subunits. Thus, TcGST1 and TcGST2 are dimeric proteins. Optimal
      TcGST1 and TcGST2 activities were observed at pH 8.5 in the range of 20-55
      degrees C and pH 7.5 at 35-40 degrees C, respectively. TcGST1 and TcGST2 were
      inhibited by cibacron blue (CB), bromosulphophthalein (BST), rose bengal (RB),
      indomethacin and haematin (Hm) with 50% inhibitory concentrations (IC50) in the
      MUm range. TcGST1 was inhibited in a non-competitive manner by all tested
      inhibitors with the exception of indomethacin, which was uncompetitive. The
      discovery of these new GSTs facilitates the potential use of T. crassiceps as a
      model to investigate multifunctional GSTs.

PMID- 29032786
TI  - CONTRIBUTION OF STAKEHOLDER ENGAGEMENT TO THE IMPACT OF A HEALTH TECHNOLOGY
      ASSESSMENT: AN IRISH CASE STUDY.
AB  - OBJECTIVES: The aim of this study was to illustrate the contribution of
      stakeholder engagement to the impact of health technology assessment (HTA) using
      an Irish HTA of a national public access defibrillation (PAD) program.
      BACKGROUND: In response to draft legislation that proposed a PAD program, the
      Minister for Health requested that Health Information and Quality Authority
      undertake an HTA to inform the design and implementation of a national PAD
      program and the necessary underpinning legislation. The draft legislation
      outlined a program requiring widespread installation and maintenance of automatic
      external defibrillators in specified premises. METHODS: Stakeholder engagement to
      optimize the impact of the HTA included one-to-one interviews with politicians,
      engagement with an Expert Advisory Group, public and targeted consultation, and
      positive media management. RESULTS: The HTA quantified the clinical benefits of
      the proposed PAD program as modest, identified that substantial costs would fall
      on small/medium businesses at a time of economic recession, and that none of the
      programs modeled were cost-effective. The Senator who proposed the Bill actively
      publicized the HTA process and its findings and encouraged participation in the
      public consultation. Participation of key stakeholders was important for the
      quality and acceptability of the HTA findings and advice. Media management
      promoted public engagement and understanding. The Bill did not progress.
      CONCLUSIONS: The HTA informed the decision not to progress with legislation for a
      national PAD program. Engagement was tailored to ensure that key stakeholders
      including politicians and the public were informed of the HTA process, the
      findings, and the advice, thereby maximizing acceptance. Appropriate stakeholder
      engagement optimizes the impact of HTA.

PMID- 29032787
TI  - Ultra-processed foods, protein leverage and energy intake in the USA.
AB  - OBJECTIVE: Experimental studies have shown that human macronutrient regulation
      minimizes variation in absolute protein intake and consequently energy intake
      varies passively with dietary protein density ('protein leverage'). According to
      the 'protein leverage hypothesis' (PLH), protein leverage interacts with a
      reduction in dietary protein density to drive energy overconsumption and obesity.
      Worldwide increase in consumption of ultra-processed foods (UPF) has been
      hypothesized to be an important determinant of dietary protein dilution, and
      consequently an ecological driving force of energy overconsumption and the
      obesity pandemic. The present study examined the relationships between dietary
      contribution of UPF, dietary proportional protein content and the absolute
      intakes of protein and energy. DESIGN: National representative cross-sectional
      study. SETTING: National Health and Nutrition Examination Survey 2009-2010.
      SUBJECTS: Participants (n 9042) aged >=2 years with at least one day of 24 h
      dietary recall data. RESULTS: We found a strong inverse relationship between
      consumption of UPF and dietary protein density, with mean protein content
      dropping from 18.2 to 13.3 % between the lowest and highest quintiles of dietary
      contribution of UPF. Consistent with the PLH, increase in the dietary
      contribution of UPF (previously shown to be inversely associated with protein
      density) was also associated with a rise in total energy intake, while absolute
      protein intake remained relatively constant. CONCLUSIONS: The protein-diluting
      effect of UPF might be one mechanism accounting for their association with excess
      energy intake. Reducing UPF contribution in the US diet may be an effective way
      to increase its dietary protein concentration and prevent excessive energy
      intake.

PMID- 29032788
TI  - Using the Bergman-Paris Question to screen seniors in the emergency department.
AB  - OBJECTIVES: In the fast pace of the Emergency Department (ED), clinicians are in
      need of tailored screening tools to detect seniors who are at risk of adverse
      outcomes. We aimed to explore the usefulness of the Bergman-Paris Question (BPQ)
      to expose potential undetected geriatric syndromes in community-living seniors
      presenting to the ED. METHODS: This is a planned sub-study of the INDEED
      multicentre prospective cohort study, including independent or semi-independent
      seniors (>=65 years old) admitted to hospital after an ED stay >=8 hours and who
      were not delirious. Patients were assessed using validated screening tests for 3
      geriatric syndromes: cognitive and functional impairment, and frailty. The BPQ
      was asked upon availability of a relative at enrolment. BPQ's sensitivity and
      specificity analyses were used to ascertain outcomes. RESULTS: A response to the
      BPQ was available for 171 patients (47% of the main study's cohort). Of this
      number, 75.4% were positive (suggesting impairment), and 24.6% were negative. To
      detect one of the three geriatric syndromes, the BPQ had a sensitivity of 85.4%
      (95% CI [76.3, 92.0]) and a specificity of 35.4% (95% CI [25.1, 46.7]). Similar
      results were obtained for each separate outcome. Odds ratio demonstrated a higher
      risk of presence of geriatric syndromes. CONCLUSION: The Bergman-Paris Question
      could be an ED screening tool for possible geriatric syndrome. A positive BPQ
      should prompt the need of further investigations and a negative BPQ possibly
      warrants no further action. More research is needed to validate the usefulness of
      the BPQ for day-to-day geriatric screening by ED professionals or geriatricians.

PMID- 29032791
TI  - Deconstructing the 4-h rule for access to emergency care and putting patients
      first.
AB  - Evidence suggests improved outcomes for patients requiring emergency admission to
      hospital are associated with improved emergency department (ED) efficiency and
      lower transit times. Factors preventing timely transfers of emergency patients to
      in-patient beds across the ED-in-patient interface are major causes for ED
      crowding, for which several remedial strategies are possible, including parallel
      processing of probable admissions, direct-to-ward admissions and single-point
      medical registrars for receiving and processing all referrals directed at
      specific speciality units. Dynamic measures of ED overcrowding that focus on
      boarding time are more indicative of EDs with exit block involving the ED-in
      patient interface than static proxy measures such as hospital bed occupancy and
      numbers of ED presentations. The ideal 4-h compliance rate for all ED
      presentations is around 80%, based on a large retrospective study of more than
      18million presentations to EDs of 59 Australian hospitals over 4 years, which
      demonstrated a highly significant linear reduction in risk-adjusted in-patient
      mortality for admitted patients as the compliance rate for all patients rose to
      83%, but was not confirmed beyond this rate. Closely monitoring patient outcomes
      for emergency admissions in addition to compliance with time-based access targets
      is strongly recommended in ensuring reforms aimed at decongesting EDs do not
      compromise the quality and safety of patient care.

PMID- 29032789
TI  - Symptom Dimensions of Depression and Apathy and Their Relationship With Cognition
      in Parkinson's Disease.
AB  - OBJECTIVES: Both depression and apathy, alone and in combination, have been shown
      to negatively affect cognition in patients with Parkinson's disease (PD).
      However, the influence of specific symptom dimensions of depression and apathy on
      cognition is not well understood. The current study investigated the relationship
      between symptom dimensions of depression and apathy, based on factors identified
      in Kirsch-Darrow et al. (2011), and memory and executive function in PD. METHODS:
      A sample of 138 non-demented individuals with PD (mean age=64.51+/-7.43 years)
      underwent neuropsychological testing and completed the Beck Depression Inventory,
      2nd Edition, and Apathy Scale. Separate hierarchical regression models examined
      the relationship between symptom dimensions of depression and apathy ("pure"
      depressive symptoms, "pure" apathy, loss of interest/pleasure [anhedonia], and
      somatic symptoms) and three cognitive domain composites: immediate verbal memory,
      delayed verbal memory, and executive function. RESULTS: After adjusting for
      general cognitive status and the influence of the other symptom dimensions,
      "pure" depressive symptoms were negatively associated with the delayed verbal
      memory composite (p<.034) and somatic symptoms were positively associated with
      the executive function composite (p<.026). No symptom dimensions were
      significantly related to the immediate verbal memory composite. CONCLUSIONS:
      Findings suggest that specific mood symptoms are associated with delayed verbal
      memory and executive function performance in non-demented patients with PD.
      Further research is needed to better understand possible mechanisms through which
      specific symptom dimensions of depression and apathy are associated with
      cognition in PD. (JINS, 2018, 24, 269-282).

PMID- 29032792
TI  - Centralisation of oesophagectomy in Australia: is only caseload critical?
AB  - Objective High caseload is considered one of the most important factors for good
      outcomes after high-risk surgeries such as oesophagectomy. However, many
      Australian centres perform low volumes of oesophagectomies due to demographics.
      The aim of the present study was to audit outcome after oesophagectomy in an
      Australian low-volume centre over a period of 13 years and to discuss potential
      contributors to outcome other than just case volume.Methods Perioperative and
      long-term outcomes of all oesophagectomies over a 13-year period in a low-volume
      Australian tertiary care centre were analysed retrospectively. Data were compared
      in subgroups of patients in two separate time periods: 2000-05 (n=23) and 2006-12
      (n=24).Results There were two perioperative deaths over the entire 13-year period
      with no postoperative mortality in the last decade. The complication and long
      term survival rates for each of the two separate time periods were similar to
      those from high-volume centres, more so in the second half of the study
      period.Conclusions The data suggest that under specific conditions,
      oesophagectomies can be safely performed even in smaller- or low-volume centres
      in Australia. The policy of centralisation for these procedures in Australia
      needs to be carefully tailored to the needs of the population, clinical outcomes,
      cost-effectiveness and optimal utilisation of existing facilities rather than on
      caseload alone.What is known about the topic? High caseload is considered one of
      the most important factors for good outcomes after oesophagectomy and a driving
      force behind centralisation of this procedure. However, other factors may also
      affect outcome - such as availability of experienced surgeons, specialist nurses,
      interventional radiology, gastroenterology, etc.What does this paper add? With
      the availability of appropriate levels of expertise, infrastructure and
      specialist nursing staff as is the case in most Australian tertiary centres, good
      perioperative outcomes can be obtained despite low volumes. Case load only should
      not be used as a surrogate marker of quality.What are the implications for
      practitioners? The policy of centralisation for oesophagectomy in Australia needs
      to be carefully thought out on the basis of population demographics, outcomes and
      cost-effectiveness, with the appropriate use of existing facilities, rather than
      on a caseload basis alone.

PMID- 29032790
TI  - Formative qualitative research to develop community-based interventions
      addressing low birth weight in the plains of Nepal.
AB  - OBJECTIVE: To explore the factors affecting intra-household food allocation
      practices to inform the development of interventions to prevent low birth weight
      in rural plains of Nepal. DESIGN: Qualitative methodology using purposive
      sampling to explore the barriers and facilitating factors to improved maternal
      nutrition. SETTING: Rural Dhanusha District, Nepal. SUBJECTS: We purposively
      sampled twenty-five young daughters-in-law from marginalised groups living in
      extended families and conducted semi-structured interviews with them. We also
      conducted one focus group discussion with men and one with female community
      health volunteers who were mothers-in-law. RESULTS: Gender and age hierarchies
      were important in household decision making. The mother-in-law was responsible
      for ensuring that a meal was provided to productive household members. The
      youngest daughter-in-law usually cooked last and ate less than other family
      members, and showed respect for other family members by cooking only when
      permitted and deferring to others' choice of food. There were limited
      opportunities for these women to snack between main meals. Daughters-in-law'
      movement outside the household was restricted and therefore family members
      perceived that their nutritional need was less. Poverty affected food choice and
      families considered cost before nutritional value. CONCLUSIONS: It is important
      to work with the whole household, particularly mothers-in-law, to improve
      maternal nutrition. We present five barriers to behaviour change: poverty; lack
      of knowledge about cheap nutritional food, the value of snacking, and cheap
      nutritional food that does not require cooking; sharing food; lack of self
      confidence; and deference to household guardians. We discuss how we have targeted
      our interventions to develop knowledge, discuss strategies to overcome barriers,
      engage mothers-in-law, and build the confidence and social support networks of
      pregnant women.

PMID- 29032800
TI  - Haemodynamic effects of incomplete stent apposition in curved coronary arteries.
AB  - Incomplete stent apposition (ISA, also known as malapposition) is a complication
      that affects day-to-day coronary stenting procedures. ISA is more prominent in
      complex arterial geometries, such as curvature, asa result of the limited
      conformability of coronary stents. These malapposed struts disturb the otherwise
      near-wall laminar blood flow and form a micro-recirculation environment. The
      micro-recirculation environment is often associated with low wall shear stress
      (WSS) and upsets the delicate balance of vascular biology, providing possible
      nidus for thrombosis and restenosis. In this study, a three-dimensional (3D)
      stent model was virtually deployed into an idealised curved coronary artery.
      Computational fluid dynamics (CFD) simulations were carried out to systematically
      analyse the haemodynamic effects of increasing maximum ISA distances, ranging
      from 180 (moderate), 400 (intermediate) to 910MUm (severe) in an artery with
      decreasing radius of curvature (ROC). Micro-recirculations around both proximal
      and distal malapposed struts become more pronounced as compared to fully-apposed
      struts. The accompanying areas of low temporally-averaged WSS (AL-TAWSS) can
      increase twofold compared to the fully-apposed condition. Furthermore,
      substantial regions (~5.2% and 9.0%) of AL-TAWSS are detached from the distal end
      of the malapposed struts in both moderate and intermediate cases respectively.
      Malapposed stents also induce more variation of TAWSS at the inner bend of the
      artery. At the stent surface, maximum WSS increases threefold from the fully
      apposed case to intermediate ISA. High WSS on the strut surface is known to
      activate platelets which when exposed to the micro-recirculation environment may
      lead to their deposition and thrombosis.

PMID- 29032801
TI  - The role of radiology in anatomy teaching in UK medical schools: a national
      survey.
AB  - AIMS: To investigate the current use of radiology in anatomy teaching across the
      UK, and to determine the level of interest expressed in expanding its role in
      medical education. MATERIALS AND METHODS: A 22-question electronic survey was
      distributed to the organisers of anatomy teaching at 35 UK medical schools. The
      questionnaire explored the use of radiology in their anatomy course, the
      different kinds of available resources, and attitudes towards integrating
      radiology into anatomy teaching. RESULTS: Responses were received from 29/35
      (83%) medical schools. Among the respondents, radiological anatomy featured in
      all but one of their curricula. Of those schools using radiology to aid anatomy
      teaching, 20/28 expressed a wish for more radiology in the curriculum.
      Timetabling constraints constituted one of the main difficulties in further
      implementation. In addition, 22/28 medical schools had already fostered
      collaborative links with local radiology departments, with 18 of these expressing
      a wish for further cooperation. Of the remaining six schools without current
      collaboration, four would like to establish connections. CONCLUSION: Compared
      with previous studies, this national survey shows a definite increase in
      radiological anatomy in medical school curricula with a stronger presence of
      radiologists in anatomy teaching. Despite this, most anatomy departments still
      express a desire to increase the radiological component in their courses.

PMID- 29032802
TI  - Radioembolisation of hepatocellular carcinoma: a primer.
AB  - Transarterial radioembolisation (TARE) has gained increasing acceptance as an
      additional/alternative locoregional treatment option for hepatocellular
      carcinoma, and colorectal hepatic metastases that present beyond potentially
      curative options. This is a catheter-based transarterial selective internal
      brachytherapy that involves injection of radioactive microspheres (usually Y-90)
      that are delivered selectively to the liver tumours. Owing to the combined
      radioactive and microembolic effect, the findings at follow-up imaging are
      significantly different from that seen with other transarterial treatment
      options. Considering increasing confidence among clinicians, refinement in
      techniques and increasing number of ongoing trials, TARE is expected to gain
      further acceptance and become an important tool in the armamentarium for the
      treatment of liver malignancies. So it is imperative that all radiologists
      involved in the management of liver malignancies are well versed with TARE to
      facilitate appropriate discussion at multidisciplinary meetings to direct further
      management. In this article, we provide a comprehensive review on various aspects
      of radioembolisation with Y-90 for hepatocellular carcinoma including the patient
      selection, treatment planning, radiation dosimetry and treatment, side effects,
      follow-up imaging and future direction.

PMID- 29032803
TI  - [Prostate cancer and DNA repair genes].

PMID- 29032804
TI  - [Clinical relevance of ESR1 circulating mutations detection in hormone receptor
      positive metastatic breast cancer].
AB  - If hormone therapy is a key treatment for hormone receptor positive advanced
      breast cancers, secondary resistance occurs as a rule. Recently, acquired
      alterations of the ESR1 gene have been identified as a mechanism of resistance on
      aromatase inhibitor (AI) treatment. The selective pressure by AI exposure during
      the metastatic setting triggers the emergence of ESR1 activating mutations. In
      that context, the "liquid biopsy" concept has been used to detect this molecular
      resistance before progression. Thus, the ESR1 circulating mutation detection will
      soon be used in daily practice to help monitoring patients on AI treatment and
      provide an early change for specific therapies that still have to be determined
      in prospective clinical trials. This review will present the acquired ESR1
      mutations, as well as the methods used for their detection in blood and the
      potential clinical impact of this approach for hormone receptor positive breast
      cancer management.

PMID- 29032805
TI  - Influence of socio-economic status and television watching on childhood obesity
      in Kolkata.
AB  - Obesity is fast becoming an epidemic among the urban children and it has its
      adverse effect on the status of health even during adulthood. In this paper an
      attempt is made to assess the percentage of obesity among 6-10 year children and
      assess the effect of different socio-economic variables and TV watching on
      childhood obesity. We restricted our study to primary school-going children who
      attended classes I-IV. The sample consisted of 5216 children from 20 different
      Bengali medium and English medium schools in Kolkata. Categorical logistic
      regression of obesity on the socio-economic factors namely type of medium school,
      religion, parent's education, duration of television watching etc., has been
      carried out. The categorical logistic regression shows the significant effect of
      some of the socio-economic or demographic variables including the duration of
      television watching on obesity. We have seen a positive association between
      obesity and TV watching and also between obesity and consumption of fast food.
      This calls for making the parents aware and taking action as early as possible.

PMID- 29032806
TI  - Multidetector computed tomography evaluation of candidates for transcatheter
      aortic valve implantation.
AB  - In transcatheter aortic valve implantation (TAVI), a biologic valve mounted in a
      stent is implanted without removing the native valve. This procedure was first
      done in humans by Alain Cribier in 2002 and was included in clinical guidelines
      after the multicenter PARTNER (Placement of AoRtic TraNscathetER) randomized
      clinical trial, which showed that TAVI obtained better outcomes than conservative
      medical treatment and is an alternative to surgery in patients with high surgical
      risk. Candidates for TAVI must be assessed to determine whether the procedure is
      feasible, because TAVI is not ideal for all patients who are considered
      inoperable. Multidetector computed tomography plays an important role in the
      anatomic evaluation of candidates and in guiding the procedure in those who are
      finally selected.

PMID- 29032807
TI  - A Comparison of the Severe Cognitive Impairment Rating Scale With the Mini-Mental
      State Examination and Delirium Rating Scale-Revised-98 for Delirium: A Cross
      sectional Study.
AB  - BACKGROUND: Cognitive impairment including attention deficits, disorientation,
      memory impairment, language disturbance, and impaired visuospatial ability are
      core symptoms of delirium. The Severe Cognitive Impairment Rating Scale (SCIRS)
      was developed to assess cognition in patients with severe dementia, but may also
      be useful in elderly people with delirium. OBJECTIVE: We investigated the use of
      the SCIRS to assess cognition in elderly patients with delirium. METHODS: We
      recruited 147 participants, aged >=65 years, referred for psychiatric
      consultation at a tertiary-care university hospital. The diagnosis and severity
      of delirium were assessed using the Korean version of the Delirium Rating Scale
      Revised-98 (K-DRS-98). Cognitive function was assessed using the SCIRS and the
      Mini-Mental State Examination (MMSE) in the Korean version of the Consortium to
      Establish a Registry for Alzheimer's Disease (CERAD) Assessment Packet (MMSE-KC).
      RESULTS: There was a strong correlation of SCIRS scores with K-DRS-98 cognition
      domain (r = -0.796), severity scores (r = -0.742), total scores (r = -0.734), and
      the MMSE-KC (r = 0.905). Analysis of variance incorporating the severity of
      delirium suggested that while the MMSE showed a floor effect, the SCIRS could
      discriminate between moderate and severe delirium. CONCLUSION: The SCIRS is a
      useful instrument to assess cognitive function in elderly patients with moderate
      to severe delirium.

PMID- 29032808
TI  - Torso geometry reconstruction and body surface electrode localization using three
      dimensional photography.
AB  - We conducted a prospective clinical study (n=14; 29% female) to assess the
      accuracy of a three-dimensional (3D) photography-based method of torso geometry
      reconstruction and body surface electrodes localization. The position of 74 body
      surface electrocardiographic (ECG) electrodes (diameter 5mm) was defined by two
      methods: 3D photography, and CT (marker diameter 2mm) or MRI (marker size
      10*20mm) imaging. Bland-Altman analysis showed good agreement in X (bias -2.5
      [95% limits of agreement (LoA) -19.5 to 14.3] mm), Y (bias -0.1 [95% LoA -14.1 to
      13.9] mm), and Z coordinates (bias -0.8 [95% LoA -15.6 to 14.2] mm), as defined
      by the CT/MRI imaging, and 3D photography. The average Hausdorff distance between
      the two torso geometry reconstructions was 11.17+/-3.05mm. Thus, accurate torso
      geometry reconstruction using 3D photography is feasible. Body surface ECG
      electrodes coordinates as defined by the CT/MRI imaging, and 3D photography, are
      in good agreement.

PMID- 29032809
TI  - Evaluation of polycyclic aromatic hydrocarbons bioavailability on Santos Bay
      (Brazil) through levels of biliary metabolites.
AB  - This study evaluated the PAH bioavailability from Santos Bay (Brazil) in 4
      species of fish, using PAH biliary metabolites. The collection was done monthly,
      between July and December, in three different regions of Santos Bay. The
      metabolites were analyzed through a high performance liquid chromatograph with
      fluorescence detectors. Total metabolites concentrations ranged from 65.5 to
      589MUgg-1 of bile, evidencing PAH bioavailability on Santos Bay. Levels of
      phenanthrene and benzo[a]pyrene metabolites were in the classification range of
      areas moderate contaminated. Those concentrations were lower in Nebris microps
      and higher in Sphoeroides testudineus (p<0.05). Naphthalene metabolites
      concentrations did not differ significantly among fish species and were in the
      classification range of low contaminated areas. There were no significant spatial
      and temporal differences in levels among sampled areas. These results are
      environmentally important given the high levels of urbanization and the absence
      of biomonitoring data in this area.

PMID- 29032810
TI  - Timely therapy requires timely diagnosis; high risk therapy demands accurate
      diagnosis.

PMID- 29032811
TI  - Editorial Comment.

PMID- 29032812
TI  - Matrix vesicles induce calcification of recipient vascular smooth muscle cells
      through multiple signaling pathways.
AB  - In patients with chronic kidney and end-stage renal diseases, the major risk
      factor for progression of arterial calcification is the presence of existing
      (baseline) calcification. Here, we tested whether calcification of arteries is
      extended from calcified vascular smooth muscle cells (VSMCs) to adjacent normal
      cells by matrix vesicle-induced alteration of cell signaling. Matrix vesicles
      isolated from VSMC of rats with chronic kidney disease were co-cultured with
      VSMCs from normal littermates. Endocytosis of vesicles by recipient cells was
      confirmed by confocal microscopy. The addition of cellular matrix vesicles with
      characteristics of exosomes and low fetuin-A content enhanced the calcification
      of recipient VSMC. Further, only cellular-derived matrix vesicles induced an
      increase in intracellular calcium ion concentration, NOX1 (NADPH oxidase) and the
      anti-oxidant superoxide dismutase-2 in recipient normal VSMC. The increase in
      intracellular calcium ion concentration was due to release from endoplasmic
      reticulum and partially attributed to the activation of both NOX1 and mitogen
      activated protein kinase (MEK1 and Erk1/2) signaling, since inhibiting both
      pathways blocked the increase in intracellular calcium ion in recipient VSMC. In
      contrast, matrix vesicles isolated from the media had no effect on the
      intracellular calcium ion concentration or MEK1 signaling, and did not induce
      calcification. However, media matrix vesicles did increase Erk1/2, although not
      to the level of cellular matrix vesicles, and NOX1 expression. Blockade of NOX
      activity further inhibited the cellular matrix vesicle-induced accelerated
      calcification of recipient VSMC, suggesting a potential therapeutic role of such
      inhibition. Thus, addition of cellular-derived matrix vesicles from calcifying
      VSMC can accelerate calcification by inducing cell signaling changes and
      phenotypic alteration of recipient VSMC.

PMID- 29032813
TI  - Light-cured Tricalcium Silicate Toxicity to the Dental Pulp.
AB  - INTRODUCTION: Numerous studies reported dentin bridge formation after pulp
      capping with tricalcium silicates. By contrast, pulp capping with resins leads to
      pulp toxicity and inflammation. Hybrid materials made up of tricalcium silicates
      and resins have also been developed to be used in direct pulp capping. This work
      was designed to study the consequences of adding resins to tricalcium silicates
      by investigating TheraCal (BISCO, Lancon De Provence, France) and Biodentine
      (Septodont, Saint Maur des Fosses, France) interactions with the dental pulp.
      METHODS: Media conditioned with the biomaterials were used to analyze pulp
      fibroblast proliferation using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide) test and proinflammatory cytokine interleukin 8 (IL
      8) secretion using the enzyme-linked immunosorbent assay. The effects of
      conditioned media on dentin sialoprotein (DSP) and nestin expression by dental
      pulp stem cells (DPSCs) were investigated by immunofluorescence. The materials'
      interactions with the vital pulp were investigated using the entire tooth culture
      model. RESULTS: TheraCal-conditioned media significantly decreased pulp
      fibroblast proliferation, whereas no effect was observed with Biodentine. When
      DPSCs were cultured with Biodentine-conditioned media, immunofluorescence showed
      an increased expression of DSP and nestin. This expression was lower with
      TheraCal, which significantly induced proinflammatory IL-8 release both in
      cultured fibroblasts and entire tooth cultures. This IL-8 secretion increase was
      not observed with Biodentine. Entire tooth culture histology showed a higher
      mineralization with Biodentine, whereas significant tissue disorganization was
      observed with TheraCal. CONCLUSIONS: Within the limits of these preclinical
      results, resin-containing TheraCal cannot be recommended for direct pulp capping.

PMID- 29032814
TI  - Healthy Dental Pulp Oxygen Saturation Rates in Subjects with Homozygous Sickle
      Cell Anemia: A Cross-Sectional Study Nested in a Cohort.
AB  - INTRODUCTION: To compare the percentage of arterial oxygen saturation (SpO2) in
      healthy teeth with confirmed pulp vitality between individuals with sickle cell
      anemia (HbSS) and normal hemoglobin A (HbAA). METHODS: This is a cross-sectional
      study nested within a cohort. Samples (n = 2543) comprised teeth with intact
      crowns and pulp vitality confirmed by thermal sensitivity tests and no history of
      caries, periodontal disease, or dental trauma. A total of 728 teeth of 113
      individuals with HbSS and 1815 teeth of 246 individuals with HbAA were evaluated.
      Data analysis was performed using the chi2 and Mann-Whitney tests and Spearman
      correlation analysis (alpha = 0.05). RESULTS: The study groups were comparable in
      terms of age, race, and sex (P > .05). Subjects with HbSS exhibited lower median
      SpO2 levels in the body and upper teeth, excluding canines, than subjects with
      HbAA (P < .05). There were no significant differences in the evaluated parameters
      between the 2 groups (P > .05). CONCLUSION: Compared with individuals with HbAA,
      those with HbSS exhibited lower SpO2 in maxillary teeth with confirmed pulp
      vitality, except in the canines. There was no correlation between SpO2 levels of
      the body and dental pulp in individuals with HbSS or HbAA.

PMID- 29032815
TI  - Effects of Rosiglitazone on the Outcome of Experimental Periapical Lesions in
      Mice.
AB  - INTRODUCTION: The purpose of this study was to evaluate a protocol for systemic
      administration of rosiglitazone in mice in order to stimulate apoptosis of
      osteocytes in the jaws and to evaluate the effect of osteocyte apoptosis induced
      by rosiglitazone in the progression of periapical lesions in mice at 7, 21, and
      42 days. METHODS: C57BL/6 mice at 4-5 weeks of age were used. In phase 1, mice (n
      = 24) were treated with rosiglitazone (gavage, 10 mg/kg dose) or without
      (phosphate-buffered saline + 10% dimethyl sulfoxide) for 1, 2, or 3 weeks. We
      used the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate
      nick-end labeling and 4'-6-diamidino-2-phenylindole methods for quantification of
      apoptotic cells. In phase 2, mice (n = 30) received rosiglitazone for 2 weeks or
      just vehicle for 1 week (n = 30), and periapical lesions were induced for 7, 21,
      or 42 days. We performed the measurement of periapical lesions, tartrate
      resistant acid phosphatase staining, dual-energy x-ray absorptiometry for the
      evaluation of bone mineral density (BMD) in long bone, and gene evaluation using
      real time quantitative polymerase chain reaction of osteocyte markers (Sost,
      Hyou1, and Dmp1) and receptor activator of nuclear factor kappa-B ligand (RANKL)
      (Tnfsf11). RESULTS: It was observed that systemic administration of rosiglitazone
      for 2 weeks showed apoptosis of osteocytes in a more expressive manner. In phase
      2, in the groups that received rosiglitazone, a trend toward larger periapical
      lesions was observed (P > .05). Rosiglitazone also induced a greater number of
      osteoclasts and a greater expression of Sost and Hyou1 at 21 days of lesions.
      Moreover, there were no statistically significant differences in RANKL and Dmp1
      expression or in the BMD of femurs. CONCLUSIONS: Rosiglitazone stimulated
      apoptosis of osteocytes, interfering in the progression of periapical lesions in
      mice.

PMID- 29032816
TI  - Physicochemical Properties and Volumetric Change of Silicone/Bioactive Glass and
      Calcium Silicate-based Endodontic Sealers.
AB  - INTRODUCTION: This study evaluated setting time (ST), radiopacity, pH, flow,
      solubility, and volumetric change (VC) of a silicone, gutta-percha, and bioactive
      glass-based sealer, GuttaFlow Bioseal (GFB), and a calcium silicate-based sealer,
      TotalFill BC Sealer (TFBC), in comparison with AH Plus. METHODS: ST and flow were
      evaluated in accordance with the ISO 6876 Standard. pH was evaluated after
      different time intervals (1, 3, 7, 14, 21, and 28 days). Radiopacity was
      evaluated by radiographic analysis in millimeters of aluminum. Solubility was
      evaluated by means of mass loss (%) after 7 and 30 days of immersion in distilled
      water. VC was evaluated by micro-computed tomography, by using cavities 3 mm deep
      and 1 mm in diameter in acrylic resin, filled with the materials. The materials
      were evaluated after setting and after 7 and 30 days of immersion in distilled
      water. The data were submitted to analysis of variance and Tukey statistical
      tests (P < .05). RESULTS: TFBC demonstrated the highest pH and solubility. GFB
      had the shortest ST, and lowest radiopacity and flow values. VC was similar for
      the sealers in both time intervals. CONCLUSIONS: TFBC presented the highest pH
      and solubility, but showed similar VC to GFB and AH Plus. GFB showed proper
      physicochemical properties. Micro-computed tomography complements the
      physicochemical analysis of endodontic sealers.

PMID- 29032817
TI  - Comparison of Alterations in the Surface Topographies of HyFlex CM and HyFlex EDM
      Nickel-titanium Files after Root Canal Preparation: A Three-dimensional Optical
      Profilometry Study.
AB  - AIMS: The aims of the present study were to examine the surface topographies of
      intact HyFlex CM and HyFlex EDM nickel-titanium files and to compare alterations
      in the surface topographies of these files after root canal preparation of
      severely curved canals of molar teeth. METHODS: Eight HyFlex CM (25/.08) and 8
      HyFlex EDM (25/.08) files were included in the present study. In total, 64
      severely curved canals of molar teeth, with curvature angles ranging between 50
      degrees  and 70 degrees , were prepared with HyFlex CM and EDM (n = 32 in each
      group). Quantitative and qualitative analyses of the files' surface deformation
      were performed by using three-dimensional optical profilometry before and after
      root canal preparation. The data were analyzed with the Student t test at the 5%
      significant level by using SPSS 21.0 software. RESULTS: In the HyFlex EDM group,
      the qualitative evaluation revealed the presence of cracks and microcavities
      after use of the file for root canal preparation, whereas only minor surface
      deformation was observed in the HyFlex CM group. The average roughness, root mean
      square roughness, and peak to valley height values of the HyFlex EDM group were
      significantly higher than those of the HyFlex CM group before and after root
      canal preparation (P < .05). The surface roughness values were statistically
      significantly increased in the HyFlex CM group after root canal preparation (P <
      .05). In contrast, the increase in the HyFlex EDM group was not statistically
      significant (P > .5). CONCLUSIONS: Within the limitations of the present study,
      the HyFlex CM files showed significantly higher surface alterations compared with
      the HyFlex EDM files after the preparation of severely curved root canals.

PMID- 29032818
TI  - Radiographic, Histologic, and Biomechanical Evaluation of Combined Application of
      Platelet-rich Fibrin with Blood Clot in Regenerative Endodontics.
AB  - INTRODUCTION: No in vivo study has been reported on the mechanical reinforcement
      of a tooth after regenerative endodontic treatment (RET). The present work aimed
      to evaluate the concurrent use of platelet-rich fibrin (PRF) with a blood clot
      (BC) in RET concerning periapical healing, root development, and tooth structural
      reinforcement. METHODS: In our study, 24 premolars from 3 beagle dogs were
      assigned into control, BC, and PRF + BC groups. Periapical healing was monitored
      with quantitative measurements of root elongation and thickening
      radiographically. Tooth biomechanical integrity was assessed with the fracture
      resistance test. Histologic evaluation was conducted. RESULTS: There was a
      significant difference among the periapical radiolucency decreasing rate of the
      control (43.75%) and the BC (100%) and PRF + BC (100%) groups (P < .05). The
      increase of root length and thickness in both the BC and PRF + BC groups was
      significantly greater than that in the control group (P < .05). No significant
      difference was detected between the 2 experimental groups regarding periapical
      healing or root development (P > .05). Teeth in the BC (249.3 +/- 64.1 N) and PRF
      + BC (281.7 +/- 37.8 N) groups had significantly higher fracture resistance than
      those in the control group (108.5 +/- 23.3 N) (P < .05). No significant
      difference was revealed between the BC and PRF + BC groups (P > .05). Histologic
      evidence of cementumlike tissue deposition along the canal wall with scattered
      bonelike tissue in the canal was observed. CONCLUSIONS: Either a combination of
      PRF with BC or BC alone could improve periapical healing, induce root
      development, and reinforce tooth structure. No additional benefit of PRF to BC in
      RET was found.

PMID- 29032819
TI  - Assessment of the Second Mesiobuccal Root Canal in Maxillary First Molars: A Cone
      beam Computed Tomographic Study.
AB  - INTRODUCTION: The purpose of this study was to investigate the incidence and
      location of the second mesiobuccal (MB2) root canal of the maxillary first molar
      and the relationship between the presence of an MB2 canal and the distribution of
      canal orifices on the pulpal floor with the aid of cone-beam computed tomographic
      (CBCT) technology. METHODS: A total of 1008 maxillary first molars (548 patients)
      were randomly selected and analyzed through CBCT imaging. The association between
      the incidence of MB2 canals and potential impacting factors including sex, side,
      age, and the distribution of the main root canal orifices on the pulpal floor was
      explored. The interorifice distances (ie, the length of a line between the center
      point of any 2 orifices) at the pulpal floor level were measured using Mimics
      10.01 software (ImageWorks, Materialise, Belgium). RESULTS: The majority of 3
      rooted maxillary first molars showed 2 root canals (85.4%) in the mesiobuccal
      root. The incidence of MB2 canals had no statistically significant difference
      between the left and right sides (P > .05) but had a significant association with
      the patients' sex and age (P < .05). Receiver operating characteristic curve
      analysis showed a high diagnostic accuracy (the area under the receiver operating
      characteristic curve = 0.92) of using the distance ratio of the interorifice
      distance between the main mesiobuccal and the palatal root canal orifices to the
      interorifice distance between the distobuccal and the palatal root canal orifices
      to predict the presence of an MB2 canal. A larger distance ratio (>1.26)
      indicated a highly probable existence of an MB2 canal. In this study, no molar
      presented an MB2 canal with a distance ratio of less than 1.16, whereas all
      molars with a ratio greater than 1.37 presented an MB2 canal without exception. A
      Bland-Altman scatterplot showed great agreement between the distances of the main
      mesiobuccal and the distobuccal canal orifices and the second mesiobuccal and the
      distobuccal canal orifices. CONCLUSIONS: Understanding the incidence of MB2
      canals and the distribution pattern of canal orifices on the pulpal floor may
      help clinicians to quickly identify and locate MB2 canals.

PMID- 29032820
TI  - Methodological Quality Assessment of Meta-analyses in Endodontics.
AB  - INTRODUCTION: The objectives of this review were to assess the methodological
      quality of published meta-analyses related to endodontics using the assessment of
      multiple systematic reviews (AMSTAR) tool and to provide a follow-up to
      previously published reviews. METHODS: Three electronic databases were searched
      for eligible studies according to the inclusion and exclusion criteria: Embase
      via Ovid, The Cochrane Library, and Scopus. The electronic search was amended by
      a hand search of 6 dental journals (International Endodontic Journal; Journal of
      Endodontics; Australian Endodontic Journal; Oral Surgery, Oral Medicine, Oral
      Pathology, Oral Radiology; Endodontics and Dental Traumatology; and Journal of
      Dental Research). The searches were conducted to include articles published after
      July 2009, and the deadline for inclusion of the meta-analyses was November 30,
      2016. The AMSTAR assessment tool was used to evaluate the methodological quality
      of all included studies. RESULTS: A total of 36 reports of meta-analyses were
      included. The overall quality of the meta-analyses reports was found to be
      medium, with an estimated mean overall AMSTAR score of 7.25 (95% confidence
      interval, 6.59-7.90). The most poorly assessed areas were providing an a priori
      design, the assessment of the status of publication, and publication bias.
      CONCLUSIONS: In recent publications in the field of endodontics, the overall
      quality of the reported meta-analyses is medium according to AMSTAR.

PMID- 29032821
TI  - 16S Ribosomal RNA Gene Sequencing to Evaluate the Effects of 6 Commonly
      Prescribed Antibiotics.
AB  - INTRODUCTION: The rapid antibiotic sensitivity test (RAST) is a novel in-office
      culture and sensitivity system for endodontic infections. The purpose of this
      research was to validate the RAST system as a viable, in-office alternative to
      antibiotic sensitivity testing using turbidity to determine antibiotic
      sensitivities of endodontic infections. METHODS: Aspirates were taken from the
      root canals of 9 necrotic human teeth at the initiation of root canal therapy.
      These samples were cultured in the RAST medium, and antibiotic sensitivity to 6
      antibiotics was tested. Further analysis was performed using 16S ribosomal RNA
      (rRNA) gene sequencing. RESULTS: Thirty-one bacterial phyla were identified as
      well as 2 phyla of the kingdom Archaea. Augmentin (Dr. Reddy's Laboratories Ltd,
      Hyderabad, India) and ampicillin performed identically at 24 hours, inhibiting
      turbidity in 100% of the samples. At 48 hours in anaerobic conditions, Augmentin
      outperformed ampicillin by 13%. Ciprofloxacin was the least efficacious
      antibiotic. At 48 hours, only 22% of anaerobic ciprofloxacin cultures affectively
      inhibited bacterial growth. CONCLUSIONS: The RAST medium is a viable in-office
      alternative to antibiotic susceptibility testing in an off-site laboratory. It is
      able to support the growth of a wide variety of microorganisms in both aerobic
      and anaerobic environments, and, in combination with 16S rRNA gene sequencing, it
      led to the identification of a new archaebacterial phylum, Crenarchaeota, as part
      of the endodontic infection microbiome.

PMID- 29032822
TI  - Evaluation of the Cytotoxicity and Biocompatibility of New Resin Epoxy-based
      Endodontic Sealer Containing Calcium Hydroxide.
AB  - INTRODUCTION: Many endodontic sealers are available, but the search for the ideal
      sealer continues. This study evaluated the cytotoxicity and biocompatibility of
      Sealer Plus, a new resin epoxy-based endodontic sealer containing calcium
      hydroxide. AH Plus, Endofill, and SimpliSeal endodontics sealers were used for
      comparison. METHODS: L929 fibroblasts were cultured, and an MTT assay was used to
      determine the cytotoxicity of the sealer extracts at 6, 24, 48, and 72 hours.
      Tubes containing materials or empty tubes for control were inserted into the
      subcutaneous tissues of 20 rats. After 7 and 30 days, the rats were killed, and
      the tubes were removed with the surrounding tissues for histologic analysis. The
      data were submitted to statistical tests (P < .05). RESULTS: Undiluted Sealer
      Plus exhibited less cytotoxicity compared with other undiluted extracts at 6
      hours (P < .05), and cell viability was higher for all Sealer Plus extracts after
      24 hours (P < .05). At 48 hours, the undiluted and 1/2 Sealer Plus dilution were
      the extracts with less cytotoxicity (P < .05). At 72 hours, cell viability was
      higher for the undiluted and 1/2 Sealer Plus dilution compared with the other
      sealers (P < .05). At 7 days, Endofill and SimpliSeal had higher inflammation
      compared with the control and Sealer Plus (P < .05); AH Plus had moderate
      inflammation (P > .05). At 30 days, control, Sealer Plus, and AH Plus had less
      inflammation (P < .05). The fibrous capsule was thick at 7 days and thin at 30
      days, except for SimpliSeal. CONCLUSIONS: In general, Sealer Plus promoted
      greater cell viability and was more biocompatible compared with the other
      sealers.

PMID- 29032823
TI  - Bortezomib Facilitates Reparative Dentin Formation after Pulp Access Cavity
      Preparation in Mouse Molar.
AB  - INTRODUCTION: The aim of this study was to evaluate in vitro and ex vivo roles of
      bortezomib, a proteasome inhibitor that binds to the active site of the 26S
      proteasome, in tertiary dentin formation. METHODS: We established pulpal access
      cavity preparation that was treated with or without bortezomib before direct pulp
      capping with a calcium hydroxide-based material. We also analyzed bone
      morphogenetic protein (Bmp)- and Wnt-related signaling molecules using
      quantitative real-time polymerase chain reaction. RESULTS: In the short-term
      observation period, the bortezomib-treated pulp specimens showed the period
      altered immunolocalization patterns of nestin, CD31, and myeloperoxidase, whereas
      the control specimens did not. The bortezomib-treated group showed a complete
      dentin bridge with very few irregular tubules after 42 days. The micro-computed
      tomographic images showed more apparent dentin bridge structures in the treated
      specimens than were in the controls. Quantitative real-time polymerase chain
      reaction analysis showed up-regulated Bmp and Wnt. CONCLUSIONS: These findings
      revealed that treatment with 1 MUmol/L bortezomib induced reparative dentin
      formation that facilitated the maintenance of the integrity of the remaining
      pulpal tissue via early vascularization and regulation of Bmp and Wnt signaling.

PMID- 29032824
TI  - The impact on survival of two different staging strategies in apparent early
      stage endometrial cancer comparing sentinel lymph nodes mapping algorithm and
      selective lymphadenectomy: An Italian retrospective analysis of two reference
      centers.
AB  - OBJECTIVE: The role of lymphadenectomy in endometrial cancer is still uncertain.
      We aimed to evaluate the survival outcomes of two different strategies in
      apparent uterine confined disease by comparing sentinel lymph node (SLN) mapping
      and selective lymphadenectomy (LD). METHODS: We retrospectively reviewed women
      with preoperative stage I endometrial cancer underwent surgical staging with
      either SLN mapping, or LD in two Italian centers. RESULTS: Eight hundred and two
      women underwent surgical staging for preoperative stage I endometrial cancer were
      revised (145 Monza; 657 Rome). All patients underwent peritoneal washing, simple
      hysterectomy with bilateral salpingo-oophorectomy and nodal staging including SLN
      mapping, or LD. Overall 8229 lymph nodes were removed (1595 in Monza, 6634 in
      Rome). Pelvic lymphadenectomy was performed in 33.1% and 52.4% in Monza and Rome,
      respectively (p<0.001). Patients with positive pelvic LN were 16.7% and 7.3%, in
      SLN and LD groups, respectively (p=0.002). Disease-free survival (DFS) curves did
      not showed a statistically significant difference between centers and strategies
      adopted (SLN mapping, LD, SLN+LD) with a HR of 0.87 (95% CI 0.63-2.16; p=0.475).
      CONCLUSIONS: Survival outcomes were similar for both strategies. The SLN strategy
      allowed to identify a higher rate of stage IIIC1 disease even with a lower median
      number of lymph node removed in SLN group. Applying a SLN algorithm does not
      impair the prognosis of endometrial cancer patients. The clinical impact and
      management of low volume metastasis in high-risk patients should be further
      clarify.

PMID- 29032825
TI  - LINE-1 retrotransposon-mediated DNA transductions in endometriosis associated
      ovarian cancers.
AB  - OBJECTIVE: Endometrioid (ENOC) and clear cell ovarian carcinoma (CCOC) share a
      common precursor lesion, endometriosis, hence the designation endometriosis
      associated ovarian cancers (EAOC). Long interspersed nuclear element 1 (LINE-1 or
      L1), is a family of mobile genetic elements activated in many cancers capable of
      moving neighboring DNA through 3' transductions. Here we investigated the
      involvement of specific L1-mediated transductions in EAOCs. METHODS: Through
      whole genome sequencing, we identified active L1-mediated transductions
      originating within the TTC28 gene in 34% (10/29) of ENOC and 31% (11/35) of CCOC
      cases. We used PCR and capillary sequencing to assess the presence of specific
      TTC28-L1 transductions in formalin-fixed paraffin-embedded (FFPE) blocks from six
      different anatomical sites (five tumors and one normal control) for four ENOC and
      three CCOC cases, and compared the results to the presence of single nucleotide
      variations (SNVs)/frame shift (fs) mutations detected using multiplex PCR and
      next generation sequencing. RESULTS: TTC28-L1 mediated transductions were
      identified in at least three tumor samplings in all cases, and were present in
      all five tumor samplings in 5/7 (71%) cases. In these cases, KRAS, PIK3CA,
      CTNNB1, ARID1A, and PTEN mutations were found across all tumor sites while other
      selected SNV/fs mutations of unknown significance were present at varying allelic
      frequencies. CONCLUSION: The TTC28-L1 transductions along with classical driver
      mutations were near ubiquitous across the tumors, suggesting that L1 activation
      likely occurred early in the development of EAOCs. TTC28-L1 transductions could
      potentially be used to determine clonal relationships and to track ovarian cancer
      progression.

PMID- 29032826
TI  - The effect of internal roughness and bonding on the fracture resistance and
      structural reliability of lithium disilicate ceramic.
AB  - OBJECTIVE: To evaluate the effect of internal roughness and bonding on the load
      to failure and structural reliability (Weibull analysis) of a lithium disilicate
      based glass ceramic under different testing scenarios. METHODS: IPS e.max CAD
      blocks (Ivoclar Vivadent AG) were shaped into cylinders (N=100), crystalized
      according to the manufacturer's instructions, and randomly assigned into two
      surface conditions: (1) polished surface (600-grit SiC polish papers), and (2) a
      roughened surface (air-abrasion with 50MUm Al2O3). Two assemblies were
      investigated: a ceramic disc isolated (to isolate the effect of roughness); and a
      simplified tri-layer setup simulating the restoration of a posterior tooth
      (ceramic+cement+epoxy resin) to evaluated the influence of bonding isolated and
      the associated effect of both factors. Four different scenarios were tested: (1)
      isolated disc under static load (n=10); (2) disc bonded to an epoxy resin
      substrate and tested under a static load (n=10); (3) disc bonded and tested under
      fatigue (n=20); and (4) simulated-bonding tested statically (n=10). The data of
      load to failure were submitted to One-way ANOVA and Weibull analysis. RESULTS: At
      a non-bonded scenario (isolated disc and simulated-bonding) a polished internal
      surface presented a higher characteristic strength. However, when bonding was
      present this difference became inexistent. No difference was found in terms of
      structural reliability (Weibull moduli) among the groups. FEA analysis shows that
      with bonding the tensile stress is better distributed, while in a non-bonded
      scenario higher tensile stresses occur at the bonding interface. SIGNIFICANCE: A
      rough internal surface impacted deleteriously the mechanical properties of
      lithium disilicate ceramic when it was not properly bonded to the substrate.
      However, bonding to the substrate appeared to play a more significant role in the
      fracture resistance than internal roughness.

PMID- 29032827
TI  - [Dislocation of the crystalline lens into the anterior chamber following
      couching: Case report].

PMID- 29032828
TI  - [A hair growing on the eye: Limbal dermoid].

PMID- 29032829
TI  - [Sixth cranial nerve palsy: Case report].

PMID- 29032830
TI  - [Corneal re-epithelialization after a thermal burn by an incandescent spatula].

PMID- 29032831
TI  - [Extrascleral extension of choroidal melanoma through a sclerotomy site].

PMID- 29032832
TI  - [Giant shield ulcer].

PMID- 29032833
TI  - [Orbital rhabdomyosarcoma associated with a varicella eruption].

PMID- 29032834
TI  - Recurrent vitreous hemorrhage secondary to capsular tension ring chafing
      syndrome: A case report.

PMID- 29032836
TI  - The impact of interferon-regulatory factors to macrophage differentiation and
      polarization into M1 and M2.
AB  - The mononuclear phagocytes control the body homeostasis through the involvement
      in resolving tissue injury and further wound healing. Indeed, local tissue
      microenvironmental changes can significantly influence the functional behavior of
      monocytes and macrophages. Such microenvironmental changes for example occur in
      an atherosclerotic plaque during all progression stages. In response to exogenous
      stimuli, macrophages show a great phenotypic plasticity and heterogeneity.
      Exposure of monocytes to inflammatory or anti-inflammatory conditions also
      induces predominant differentiation to proinflammatory (M1) or anti-inflammatory
      (M2) macrophage subsets and phenotype switch between macrophage subsets. The
      phenotype transition is accompanied with great changes in the macrophage
      transcriptome and regulatory networks. Interferon-regulatory factors (IRFs) play
      a key role in hematopoietic development of monocytes, their differentiation to
      macrophages, and regulating macrophage maturation, phenotypic polarization,
      phenotypic switch, and function. Of 9 IRFs, at least 3 (IRF-1, IRF-5, and IRF-8)
      are involved in the commitment of proinflammatory M1 whereas IRF-3 and IRF-4
      control M2 polarization. The role of IRF-2 is context-dependent. The IRF impact
      on macrophage phenotype plasticity and heterogeneity is complex and involves
      activating and repressive function in triggering transcription of target genes.

PMID- 29032835
TI  - Spatial Intensity Distribution Analysis: Studies of G Protein-Coupled Receptor
      Oligomerisation.
AB  - Spatial intensity distribution analysis (SpIDA) is a recently developed approach
      for determining quaternary structure information on fluorophore-labelled proteins
      of interest in situ. It can be applied to live or fixed cells and native tissue.
      Using confocal images, SpIDA generates fluorescence intensity histograms that are
      analysed by super-Poissonian distribution functions to obtain density and quantal
      brightness values of the fluorophore-labelled protein of interest. This allows
      both expression level and oligomerisation state of the protein to be determined.
      We describe the application of SpIDA to investigate the oligomeric state of G
      protein-coupled receptors (GPCRs) at steady state and following cellular
      challenge, and consider how SpIDA may be used to explore GPCR quaternary
      organisation in pathophysiology and to stratify medicines.

PMID- 29032837
TI  - Accelerated reactivity of blood granulocytes in patients with atopic bronchial
      asthma out of exacerbation.
AB  - Reactive oxygen species (ROS) are important in bronchial asthma (BA) pathogenesis
      owing to accumulation of activated granulocytes in the lungs. But the ROS
      producing activity of the cells is insufficiently understood in the blood of BA
      patients. This study analyzes the kinetics of phagocyte respiratory burst in the
      blood to improve the methods of BA patients monitoring. Patients with atopic BA
      out of exacerbation (n=60) and healthy controls (n=43) were recruited. The time
      course of respiratory response to opsonized zymosan (OZ) was recorded in the
      whole blood using luminol-dependent chemiluminescence (CL), and its activation
      kinetics (lag-time, rate, amplitude, ROS production) was calculated. The
      discriminative power of ROS generation kinetics was defined by Receiver Operating
      Characteristic (ROC) curve analysis. Standard physiological respiratory
      parameters of patients did not differ from the controls. More rapid response to
      OZ was recorded in BA patient samples versus the controls. The primed state of
      phagocytes in the blood of BA patients was corroborated by significant weakening
      formyl peptide priming effect. The adhesion of granulocytes to cultured human
      endothelial cells was two-fold higher in BA patients versus controls. ROC curve
      analysis exhibited good discriminative effectiveness of the CL kinetics to
      compare BA individuals with the controls. The highest power (86% sensitivity and
      90% specificity) was achieved at a linear combination of the parameters. We
      assume that the assessment of phagocyte reactivity based on the analysis of the
      response kinetic profile is a good test for monitoring of the state in BA
      patients.

PMID- 29032838
TI  - Next generation of microbiological risk assessment: Potential of omics data for
      exposure assessment.
AB  - In food safety and public health risk evaluations, microbiological exposure
      assessment plays a central role as it provides an estimation of both the
      likelihood and the level of the microbial hazard in a specified consumer portion
      of food and takes microbial behaviour into account. While until now mostly
      phenotypic data have been used in exposure assessment, mechanistic cellular
      information, obtained using omics techniques, will enable the fine tuning of
      exposure assessments to move towards the next generation of microbiological risk
      assessment. In particular, metagenomics can help in characterizing the food and
      factory environment microbiota (endogenous microbiota and potentially pathogens)
      and the changes over time under the environmental conditions associated with
      processing, preservation and storage. The difficulty lies in moving up to a
      quantitative exposure assessment, because the development of models that enable
      the prediction of dynamics of pathogens in a complex food ecosystem is still in
      its infancy in the food safety domain. In addition, collecting and storing the
      environmental data (metadata) required to inform the models has not yet been
      organised at a large scale. In contrast, progress in biomarker identification and
      characterization has already opened the possibility of making qualitative or even
      quantitative connection between process and formulation conditions and microbial
      responses at the strain level. In term of modelling approaches, without changing
      radically the usual model structure, changes in model inputs are expected:
      instead of (or as well as) building models upon phenotypic characteristics such
      as for example minimal temperature where growth is expected, exposure assessment
      models could use biomarker response intensity as inputs. These new generations of
      strain-level models will bring an added value in predicting the variability in
      pathogen behaviour. Altogether, these insights based upon omics techniques will
      increase our (quantitative) knowledge on pathogenic strains and consequently will
      reduce our uncertainty; the exposure assessment of a specific combination of
      pathogen and food will be then more accurate. This progress will benefit the
      whole community of safety assessors and research scientists from academia,
      regulatory agencies and industry.

PMID- 29032839
TI  - Alternative terminology for the confusing term "palliative nutrition".

PMID- 29032840
TI  - Soybean: A potential economic dietary supplement for patients sustaining
      Traumatic Brain Injury.

PMID- 29032841
TI  - Circulating fatty acids in relation to alcohol consumption: Cross-sectional
      results from a cohort of 60-year-old men and women.
AB  - BACKGROUND & AIMS: Alcohol consumption is considered to affect circulating fatty
      acids (FAs) but knowledge about specific associations is limited. We aimed to
      assess the relation between alcohol consumption and serum FAs in 60-year-old
      Swedish men and women. METHODS: In a random sample of 1917 men and 2058 women
      residing in Stockholm county, cross-sectional associations between different
      categories of alcohol consumption and FAs were assessed using linear regression;
      beta1 coefficients with 95% confidence interval (CI) were calculated. Self
      reported alcohol consumption was categorized as none, low (<=9.9 g/day)
      (reference), moderate (10-29.9 g/day) and high (>=30 g/day). Moderate alcohol
      consumption was further subdivided into consumption of beer, wine, liquor and
      their combinations. Thirteen serum cholesterol ester FAs were measured by gas
      chromatography and individual FAs were expressed as percentage of total FAs.
      RESULTS: Increasing alcohol consumption was associated to linear increase of
      saturated myristic acid, monounsaturated FAs and n-6 polyunsaturated (PUFA)
      arachidonic acid, whereas linear decrease was noted for saturated pentadecanoic
      acid and for n-6 PUFA linoleic acid. With non-linear associations, increasing
      alcohol consumption also associated to decreased saturated stearic acid, n-6 PUFA
      dihomo-gamma-linolenic acid, and n-3 PUFA docosahexaenoic acid and increased
      saturated palmitic acid, n-6 PUFA gamma-linolenic acid and n-3 PUFA
      eicosapentaenoic acid. Among types of beverages, wine consumption was associated
      with n-6 PUFA arachidonic acid (beta1 0.59; 95% CI: 0.30;0.88) and the n-3 PUFAs
      eicosapentaenoic acid (beta1 0.54; 95% CI: 0.30;0.78), and docosahexaenoic acid
      (beta1 0.06; 95% CI: 0.00;0.12). CONCLUSIONS: These findings may give important
      basis for further investigations to better understand biological mechanisms
      behind the dose-dependent associations between alcohol consumption and health
      outcomes observed in many previous studies.

PMID- 29032843
TI  - The 'Evo-Demo' Implications of Condition-Dependent Mortality.
AB  - Animals in the wild die from a variety of different mortality sources, including
      predation, disease, and starvation. Different mortality sources selectively
      remove individuals with different body condition in different ways, and this
      variation in the condition dependence of mortality has evolutionary and
      demographic implications. Subsequent population dynamics are influenced by the
      strength of condition-dependent mortality during specific periods, with
      population growth impacted in different ways in short- versus long-lived species.
      The evolution of lifespan is strongly influenced by condition-dependent
      mortality, with strikingly different outcomes expected in senescence rates when
      the relationship between condition and mortality is altered. A coupling of field
      and laboratory studies is now required to further reveal the evolutionary
      implications of condition-dependent mortality.

PMID- 29032844
TI  - [Family adherence in serious mental disorder].
AB  - OBJECTIVE: Identify attitudes and behaviors that evidence and characterize family
      adherence to treatment in patients with severe mental disorder. DESIGN:
      Qualitative descriptive, from an interpretative social approach. LOCATION: Chia,
      Colombia, with professionals in the psychiatric and geriatric settings.
      PARTICIPANTS: Twelve professionals in psychiatry, nursing and psychology, with
      experience in care of patients with serious mental disorder and their families.
      METHOD: Intentional sampling. Twelve semi-structured interviews were carried out.
      The analysis strategy was made from the procedures of constant comparison and
      open coding of the grounded theory. As validation strategies, triangulation was
      done between researchers and methods, as interviews and results survey. RESULTS:
      Two categories of family adherence were defined: family and treatment (treatment
      cooperation, knowledge about the disease and attention to the disease evolution),
      and family attitudes towards the patient (patient's care, patient's promotion of
      autonomy, and affective attachment with the patient). A third category showed
      aspects that diminished family adherence, such as lack or distortion of
      information regarding mental disorder, or family and patient endurance attitudes.
      CONCLUSIONS: Participants agree about the relevance of the construct named
      "family adherence", which describes the behaviors and attitudes of the family
      regarding the treatment of patients with severe mental disorder. Family adherence
      can be seen as active participation behavior, but also as a process of
      strengthening relationships, which can reduce the burden and suffering on family
      members, caregivers and patients.

PMID- 29032842
TI  - Making Dopamine Connections in Adolescence.
AB  - A dramatic maturational process ongoing in adolescence is prefrontal cortex
      development, including its dopamine innervation. Dopamine axons grow from the
      striatum to the prefrontal cortex, the only known case of long-distance axon
      growth during adolescence. This is coordinated by the Netrin-1 guidance cue
      receptor DCC (deleted in colorectal cancer), which in turn controls the intrinsic
      development of the prefrontal cortex itself. Stimulant drugs in adolescence alter
      DCC in dopamine neurons and, in turn prefrontal cortex maturation, impacting
      cognitive abilities. Variations in DCC expression are linked to psychiatric
      conditions of prefrontal cortex dysfunction, and microRNA regulation of DCC may
      be key to determining adolescent vulnerability or resilience. Since early
      interventions are proving to effectively ameliorate disease outcome, the Netrin-1
      system is a promising therapeutic target.

PMID- 29032845
TI  - [Frequent attendance in a Primary Health Care District].
AB  - OBJECTIVE: To describe the distribution of frequent attenders (FA) through the
      different primary care practices in Cordoba-Guadalquivir Health District
      (Cordoba, Spain). METHODS: An ecological study was performed, including data from
      2011 to 2015. Defining FA as those subjects who made12 or more appointments per
      year; independently analysed for nursing, general practice and paediatrics.
      Prevalence of frequent attendance and FA/professional ratio were used as
      dependent variables. Demographic characteristics from district population, number
      of health professionals and use of general facilities were also examinated.
      Aiming to understand FA distribution, primary health settings were classified
      according to facility size and environmental location (urban, suburban and
      rural). RESULTS: The mean prevalence for FA was 10.86% (0.5 SE) for nursing;
      general practice 21.70% (0.7 SE) and for paediatrics 16.96% (0.7 SE).
      FA/professional ratios for the different professional categories were: 101.07
      (5.0 SE) for nursing, 239.74 (9.0 SE) for general practice and 159.54 (9.8 SE)
      for paediatrics. CONCLUSIONS: A major part of primary health care users make a
      high number of consultations. From this group, women overuse nursing and general
      practitioner services more compared to men. A higher prevalence of FAs was
      observed in smaller settings, in rural areas. Although taking the
      FAs:professional ratio as the bar, medium-size practices are more highly
      overused.

PMID- 29032846
TI  - Re: Sophia C. Kamran, Thomas Seisen, Sarah C. Markt, et al. Contemporary
      Treatment Patterns and Outcomes for Clinical Stage IS Testicular Cancer. Eur Urol
      2018;73:262-70.

PMID- 29032847
TI  - Management of a Renal Mass in a Solitary Kidney: To Freeze or To Cut?

PMID- 29032848
TI  - [Ehlers-Danlos syndromes].
AB  - Ehlers-Danlos syndromes (EDS) are a heterogeneous group of inheritable connective
      tissue disorders characterized by skin hyperextensibility, joint hypermobility
      and cutaneous fragility with delayed wound healing. Over and above these common
      features, they differ in the presence or absence of various organ and tissue
      abnormalities, and differences in genetic causal mechanisms and degree of
      severity. They are complex and multisystem diseases, with the majority being
      highly disabling because of major joint problems and neurosensory deficiencies,
      and in some cases, they may be life-threatening due to associated complications,
      especially vascular disorders. In 1997, the Villefranche classification defined 6
      subtypes of EDS. However, many other new variants have been described over the
      last years. The "historical" EDS were characterized by abnormalities in fibrillar
      collagen protein synthesis. More recently, disorders of synthesis and
      organization of the extracellular matrix have been shown to be responsible for
      other types of EDS. Thus, many EDS are in fact metabolic diseases related to
      enzymatic defects. While there is no curative treatment for any type of EDS,
      early diagnosis is of utmost importance in order to optimize the symptomatic
      management of patients and to prevent avoidable complications. Patients must be
      treated and monitored by multidisciplinary teams in highly specialized reference
      centers. In this article, we present the current state of knowledge on these
      diseases that continue to be elucidated thanks to new molecular genetic
      techniques.

PMID- 29032849
TI  - Mapping the Landscape of Patient-centric Activities Within Clinical Research.
AB  - PURPOSE: Although there has been more involvement by patients in the drug
      development process, there are not a lot of published data that quantify patient
      centric activities or that document these activities across a large scale. In
      order to examine the patient-centricity landscape and to quantify the adoption
      and implementation of these initiatives, the Tufts Center for the Study of Drug
      Development and the Drug Information Association collaborated on a research
      study. The study examined patient-centric activities implemented by
      pharmaceutical, biotechnology, and contract research organizations, as well as
      activities being piloted or in the planning stages. METHODS: A global industry
      survey was conducted across pharmaceutical, biotechnology, and contract research
      organizations, assessing 25 patient-centric activities within clinical research.
      Some of these initiatives involve the use of social media to engage with
      patients, or the use of social listening to monitor study activity. Initiatives
      being implemented, planned, or piloted in addition to those not being considered
      were evaluated by respondents. Twenty-two unique companies responded to the
      survey, representing a mix of large, mid-sized, and small organizations.
      FINDINGS: The most widely adopted patient-centric initiatives, including
      activities both implemented and piloted across organizations, were patient
      advisory boards (17/22 companies), professional panels (16), lay-language
      clinical trial results summaries (13), assessment of the patient-organization
      landscape (10), and the use of home nursing networks (9). IMPLICATIONS: The
      results of the study suggest that organizations have a varied approach to the
      adoption and implementation of patient-centric initiatives, with more activities
      occurring in the planning stages than are being piloted or implemented. Many
      factors affect implementation and adoption, including buy-in by senior
      management, organizational vision, resources, and level of investment.

PMID- 29032850
TI  - Impact of Penicillin Allergy on Time to First Dose of Antimicrobial Therapy and
      Clinical Outcomes.
AB  - PURPOSE: The objective of this study was to evaluate the impact of a listed
      penicillin allergy on the time to first dose of antibiotic in a Veterans Affairs
      hospital. Additional clinical outcomes of patients with penicillin allergies were
      compared with those of patients without a penicillin allergy. METHODS: A
      retrospective chart review of veterans admitted through the emergency department
      with a diagnosis of pneumonia, urinary tract infection, bacteremia, and sepsis
      from January 2006 to December 2015 was conducted. The primary outcome was time to
      first dose of antibiotic treatment, defined as the time from when the patient
      presented to the emergency department to the medication administration time.
      Secondary outcomes included total antibiotic therapy duration and treatment
      outcomes, including mortality, length of stay, and 30-day readmission rate.
      FINDINGS: A total of 403 patients were included in the final analysis; 57
      patients (14.1%) had a listed penicillin allergy. The average age of the
      population was 75 years and 99% of the population was male. The mean time to
      first dose of antibiotic treatment for patients with a penicillin allergy was
      prolonged compared with those without a penicillin allergy (236.1 vs 186.6
      minutes; P = 0.03), resulting in an approximately 50-minute delay. Penicillin
      allergic patients were more likely to receive a carbapenem or fluoroquinolone
      antibiotic (P < 0.0001). IMPLICATIONS: Patients with a penicillin allergy had a
      prolonged time to first dose of antibiotic therapy. No significant differences
      were found in total antibiotic duration, length of stay, or 30-day readmission
      rate. The small sample size, older population, and single-center nature of this
      study may limit the generalizability of the present findings to other
      populations.

PMID- 29032851
TI  - Foreword.

PMID- 29032852
TI  - Limited influence of primary treated sewage waters on bacterial abundance,
      production and community composition in coastal seawaters.
AB  - The response of bacteria in terms of abundance, production and community
      structure to changes induced by the discharge of primary treated sewage waters
      was investigated combining microbiological, chemical and molecular tools. The
      primary treatment did not affect substantially the bacterial community structure
      in wastewaters and did not reduce the concentrations of fecal indicators. The
      spatial distribution of the sewage plume was governed by vertical stratification
      and currents. Bacterial abundance and production in the sea receiving waste
      waters depended predominantly on environmental conditions. In the waters with the
      highest concentration of fecal pollution indicators the bacterial community was
      characterized by allochthonous bacteria belonging to Epsilonproteobacteria,
      Firmicutes, Gammaproteobacteria and Bacteroidetes. The latter two taxa were also
      present in unpolluted waters but had a different structure, typical for
      oligotrophic environments. Although the impact of primary treated sewage waters
      was limited, a sanitary risk persisted due to the relevant presence of
      potentially pathogenic bacteria.

PMID- 29032854
TI  - Intrasinusal locking technique: a novel use of the ring block technique at sinus
      perforations for simultaneous implant placement.
AB  - Ten patients who underwent sinus lift surgery with simultaneous implant placement
      using the intrasinusal locking technique were evaluated retrospectively. All
      patients were scheduled for sinus floor elevation procedures with simultaneous
      implant placement. Schneiderian membrane perforation occurred during the lifting
      procedure, and conventional methods failed to repair the perforation. Therefore,
      an autogenous bone ring was placed at the base of the maxillary sinus and was
      locked to the alveolar crest with a dental implant. Marginal resorption around
      the dental implants was measured on panoramic radiographs. Prosthetic
      rehabilitation was performed at 6 months postoperative. The overall survival rate
      of the implants over a mean follow-up of 24.3 months was 90%. One case failed due
      to resorption of the alveolar crest around the implant as a result of infection;
      the implant and the adjacent ring were removed at 1 month postoperative. At the
      time of writing, the nine implants placed using the documented technique continue
      to function well, without any signs of peri-implant disease. The proposed
      approach allows for simultaneous dental implant placement in the extremely
      atrophic maxilla, even if there is extensive perforation of the Schneiderian
      membrane.

PMID- 29032853
TI  - Genetic Polymorphisms of CFH and ARMS2 Do Not Predict Response to Antioxidants
      and Zinc in Patients with Age-Related Macular Degeneration: Independent
      Statistical Evaluations of Data from the Age-Related Eye Disease Study.
AB  - PURPOSE: Considerable controversy has erupted in recent years regarding whether
      genotyping should be part of standard care for patients with age-related macular
      degeneration (AMD) who are being considered for treatment with antioxidants and
      zinc. We aimed to determine whether genotype predicts response to supplements in
      AMD. DESIGN: Three separate statistical teams reanalyzed data derived from the
      Age-Related Eye Disease Study (AREDS), receiving data prepared by the AREDS
      investigators and, separately, data from investigators reporting findings that
      support the use of genotyping. PARTICIPANTS: The population of interest was AREDS
      participants with AMD worse than category 1 and genotyping data available. Data
      from the 2 groups overlap imperfectly with respect to measurements made: the
      largest common set involved 879 participants for whom the same CFH and ARMS2
      single nucleotide polymorphisms were measured by both groups. METHODS: Each team
      took a separate but complementary approach. One team focused on data concordance
      between conflicting studies. A second team focused on replicating the key claim
      of an interaction between genotype and treatment. The third team took a blank
      slate approach in attempting to find baseline predictors of treatment response.
      MAIN OUTCOME MEASURES: Progression to advanced AMD. RESULTS: We found errors in
      the data used to support the initial claim of genotype-treatment interaction.
      Although we found evidence that high-risk patients had more to gain from
      treatment, we were unable to replicate any genotype-treatment interactions after
      adjusting for multiple testing. We tested 1 genotype claim on an independent set
      of data, with negative results. Even if we assumed that interactions in fact did
      exist, we did not find evidence to support the claim that supplementation leads
      to a large increase in the risk of advanced AMD in some genotype subgroups.
      CONCLUSIONS: Patients who meet criteria for supplements to prevent AMD
      progression should be offered zinc and antioxidants without consideration of
      genotype.

PMID- 29032855
TI  - SPECT bone scintigraphy for the assessment of condylar growth activity in
      mandibular asymmetry: is it accurate?
AB  - The comparison of serial radiographs and clinical photographs is considered the
      current accepted standard for the diagnosis of active condylar hyperplasia in
      patients with facial asymmetry. Single photon emission computed tomography
      (SPECT) has recently been proposed as an alternative method. SPECT can be
      interpreted using three reported methods absolute difference in uptake, uptake
      ratio, and relative uptake. SPECT findings were compared to those from serial
      comparisons of radiographs and clinical photographs taken at the time of SPECT
      and a year later; the sensitivities and specificities were determined. Two
      hundred patient scans were evaluated. Thirty-four patients showed active growth
      on serial growth assessment. On comparison with serial growth assessment, the
      sensitivity and specificity of the three methods ranged between 32.4% and 67.6%,
      and 36.1% and 78.3%, respectively. Analysis using receiver operating
      characteristic (ROC) curves revealed area under the curve (AUC) values of <0.58.
      The average age (mean+/-standard deviation) of patients with active growth was
      18.6+/-2.8 years, and average growth in the anteroposterior, vertical, and
      transverse directions was 0.94+/-0.91mm, 0.88+/-0.86mm, and 1.4+/-0.66 mm,
      respectively. With such low sensitivity and specificity values, it is not
      justifiable to use SPECT in place of serial growth assessment for the
      determination of condylar growth status.

PMID- 29032857
TI  - Department of Error.

PMID- 29032858
TI  - Treaty to prohibit nuclear weapons: towards safeguarding humanity.

PMID- 29032856
TI  - Sedentary Time, Physical Activity, and Adiposity: Cross-sectional and
      Longitudinal Associations in CARDIA.
AB  - INTRODUCTION: Higher sedentary time (ST) and lower moderate- to vigorous
      intensity physical activity (MVPA) have each been associated with greater
      adiposity, but most studies are cross-sectional and measure ST and MVPA by self
      report. This study evaluated associations between objective ST and MVPA with
      current and 5-year changes in BMI and waist circumference. METHODS: The Coronary
      Artery and Risk Development in Young Adults longitudinal cohort study recruited
      black or white young adults from four U.S. cities. This analysis (conducted in
      2016) used data from 2005 to 2006 as baseline and 2010 to 2011 as 5-year follow
      up. Accelerometers measured baseline ST (total and prolonged in bouts of >=10
      minutes) and MVPA (bouts of >=10 minutes). BMI and waist circumference were
      assessed at baseline and repeated 5 years later. Regression models included
      sedentary time and MVPA simultaneously with adjustment for demographics and
      lifestyle factors. RESULTS: Participants (n=1,826) were 57% female; 40% black;
      aged 38-50 years; and had a BMI of 28.7 (SD=6.3). At baseline, total and
      prolonged ST were directly associated with BMI and waist circumference, whereas
      MVPA was inversely related (all p<0.05). Longitudinally, only prolonged ST (per
      hour/day) was associated with greater increases in BMI (0.077, p=0.033) and waist
      circumference (0.198 cm, p=0.028). Associations between ST and adiposity were
      more apparent in less active participants. Risk of >=5% increase in BMI across
      assessments increased by 8%-10% (p<0.05) per hour/day of ST. CONCLUSIONS: Time
      spent sedentary was associated with increases in adiposity over time. Reducing
      sedentary time may be a novel strategy for weight control.

PMID- 29032859
TI  - The effect of maternal DHA supplementation on body fat mass in children at 7
      years: follow-up of the DOMInO randomized controlled trial.
AB  - BACKGROUND: Animal studies have suggested that an increased supply of omega-3
      long chain polyunsaturated fatty acids (LCPUFA), in particular docosahexaenoic
      acid (DHA), during the perinatal period can prevent later excess body fat mass.
      However, previous human studies have produced inconsistent findings, and few have
      assessed potential effects beyond 6 years of age. OBJECTIVE: To evaluate the
      effect of supplementing women in the second half of pregnancy with omega-3
      LCPUFA, chiefly as DHA, on the percentage body fat of children at 7 years of age,
      as assessed by two methods: air displacement plethysmography (BOD POD) and
      bioelectrical impedance spectroscopy (BIS). DESIGN: A time-restricted follow up
      at 7 years of age of children born to mothers enrolled in DOMInO (DHA to Optimise
      Maternal Infant Outcome) randomized controlled trial, in which women took either
      high-DHA tuna oil (800mg/day DHA) or placebo capsules from 20 weeks' gestation to
      delivery, at Adelaide-based centers. Primary outcomes were the percentage body
      fat at 7 years of age as assessed by both BOD POD and BIS. Weight, height,
      waist/hip circumferences and BMI were also recorded. RESULTS: A total of 252
      DOMInO children (n=135 males, n=117 females) completed the follow up study. There
      were no differences between the DHA and placebo groups in percentage body fat as
      assessed by either BOD POD [adjusted mean difference: -0.35, 95% CI: -1.46, 2.16;
      P=0.71] or BIS [adjusted mean difference: 0.64, 95% CI: -0.99, 2.27; P=0.44]. BMI
      z-scores were also similar between groups [adjusted mean difference: 0.18, 95%
      CI: -0.10, 0.45; P=0.21]. There were also no differences in height, weight or
      waist and hip circumference between the DHA and placebo groups at 7 years of age.
      CONCLUSION: DHA supplementation in the second half of pregnancy has no effect on
      childhood growth or fat mass at 7 years of age, supporting findings from follow
      ups of the DOMInO children at 3 and 5 years.

PMID- 29032860
TI  - Biomechanical comparison of two different locking plates for open wedge high
      tibial osteotomy.
AB  - BACKGROUND: The purpose of this study was to compare the mechanical stability of
      a relatively thin locking plate (FlexitSystem implant) with a relatively firm
      locking plate (TomoFix implant), both used for opening wedge high tibial
      osteotomy. METHODS: Seven fresh frozen paired human cadaveric tibiae were used.
      The opening wedge high tibial osteotomies in the left tibiae were fixated with
      the FlexitSystem implant and in the right tibiae with the TomoFix implant. The
      tibiae were CT-scanned to determine the bone mineral density. Axial loading was
      applied in a cyclic fashion for 50,000 cycles. We compared throughout the loading
      history the relative motions between the proximal and distal tibia using roentgen
      stereophotogrammetry analysis at set intervals. Also the strength of the
      reconstructions was compared using a displacement-controlled compressive test
      until failure. RESULTS: One pair (with the lowest bone mineral density) failed
      during the preparation of the osteotomy. The FlexitSystem implant displayed a
      similar stability compared to the TomoFix implant, with low translations (mean
      2.16 +/- 1.02 mm vs. 4.29 +/- 5.66 mm) and rotations (mean 3.17 +/- 2.04 degrees 
      vs. 4.30 +/- 6.78 degrees ), which was not significant different. Although on
      average the FlexitSystem reconstructions were slightly stronger than the Tomofix
      reconstructions (mean 4867 +/- 944 N vs. 4628 +/- 1987 N), no significant (p =
      0.71) differences between the two implants were found. CONCLUSION: From a
      biomechanical point of view, the FlexitSystem implant is a suitable alternative
      to the TomoFix implant for a high tibial open wedge osteotomy.

PMID- 29032861
TI  - Patellar Resurfacing in Total Knee Arthroplasty: Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: Patellar resurfacing in total knee arthroplasty remains
      controversial. The aim of this study is to evaluate this technique through an
      analysis of comparative studies in the current literature. METHODS: We performed
      a comprehensive search of PubMed, MEDLINE, Cochrane, CINAHL, and EMBASE databases
      using various combinations of the keywords "Knee," "Replacement," "Prosthesis,"
      "Patella," "Resurfacing," and "Arthroplasty." All articles relevant to the
      subject were retrieved, and their bibliographies were hand searched for further
      references relevant to primary patellar resurfacing in total knee arthroplasty.
      Only articles published in peer-reviewed journals were included in this
      systematic review. RESULTS: The percentage for a reoperation was 1% for the
      patellar resurfacing group (17/1636) and 6.9% for the non-resurfacing group
      (118/1699) (odds ratio [OR] 0.18, 95% confidence interval [CI] 0.11-0.29, P <
      .00001). The patellar resurfacing group showed a significantly higher postop Knee
      Society Score (KSS) pain (OR 1.52, 95% CI 0.68-2.35, P = .004) and postop
      Hospital for Special Surgery score (OR 4.35, 95% CI 3.21-5.49, P < .00001), over
      the non-resurfacing group. CONCLUSION: Based on the outcome scores of KSS (pain),
      KSS (function), and Hospital for Special Surgery postop, patellar resurfacing
      TKAs have performed better than non-resurfaced TKAs. The lower secondary
      operation and revision rates for patellar resurfaced TKAs also demonstrate that
      this technique is the more effective option. However, the full impact of patellar
      resurfacing still needs to be critically evaluated by larger randomized
      controlled trials with long-term follow-up.

PMID- 29032862
TI  - Endovascular treatment of acute tandem occlusion strokes and stenting first
      experience.
AB  - This study demonstrates the radiologic and clinical findings, etiologies and
      intervention strategy in 8 acute ischemic stroke patients with tandem occlusions.
      The mean age was 57 and mean NIHSS score was 19. Stent-assisted thrombectomy
      (SAT) was performed on all of the patients. Additionally, 6 patients underwent
      carotid artery stenting before SAT. Recanalization with TICI>=2b was attained in
      7/8 patients. The 90thday median mRS was 2 and mortality was 1/8. The etiologies
      of the tandem occlusions were either extracranial high grade ICA
      stenosis/occlusion or cervical ICA dissection. When the stent-first approach was
      applied with distal thrombectomy, high TICI and low mRS scores were obtained.

PMID- 29032863
TI  - Measuring the Quality of Personal Care in Patients Undergoing Radiotherapy for
      Prostate Cancer.
AB  - AIMS: To describe the quality of the non-technical component of the care
      (personal care) of patients receiving radical radiotherapy for prostate cancer
      and to identify elements of personal care that should be priorities for quality
      improvement. MATERIALS AND METHODS: One hundred and eight patients undergoing
      radiotherapy for localised prostate cancer completed a self-administered
      questionnaire that asked them to rate the importance of 143 non-technical
      elements of care and to rate the quality of their own care with respect to each
      element. The elements that a patient rated as both 'very important' and less than
      'very good' were deemed to be his priorities for improvement. The priorities of
      the population were established by ranking the elements based on the percentage
      of patients who identified them as a priority (importance/quality analysis).
      RESULTS: The response rate was 65%. The percentage of elements rated 'very good'
      varied from patient to patient: median 79% (interquartile range 69-92%). The
      percentage of elements rated either 'very good' or 'good' was higher: median 96%
      (interquartile range 86-98%). Nonetheless, almost every patient rated at least
      some elements of his care as less than optimal, regardless of the cut-off point
      used to define optimal quality. Patients assigned their lowest quality ratings to
      elements relating to the quality of the treatment environment and
      comprehensiveness of additional services available to them. However, patients
      rated most of these elements as relatively unimportant, and importance/quality
      analysis identified elements of care relating to communication of information
      about the disease and its treatment as the highest priorities for quality
      improvement. CONCLUSIONS: Most patients rated most elements of their personal
      care as very good, but almost all were able to identify some elements that were
      less than optimal. When ratings of quality were integrated with ratings of
      importance, elements relating to communication emerged as the patients' highest
      priorities for quality improvement.

PMID- 29032864
TI  - Dietary variation and mechanical properties of articular cartilage in the
      temporomandibular joint: implications for the role of plasticity in
      mechanobiology and pathobiology.
AB  - Due to their nature as tissue composites, skeletal joints pose an additional
      challenge in terms of evaluating the functional significance of morphological
      variation in their bony and cartilaginous components in response to altered
      loading conditions. Arguably, this complexity requires more direct means of
      investigating joint plasticity and performance than typically employed to analyze
      macro- and micro-anatomical phenomena. To address a significant gap in our
      understanding of the plasticity of the mammalian temporomandibular joint (TMJ),
      we investigated the histology and mechanical properties of condylar articular
      cartilage in rabbits subjected to long-term variation in diet-induced masticatory
      stresses, specifically cyclical loading. Three cohorts of male weanlings were
      raised for six months on different diets until adulthood. Following euthanasia,
      the TMJ condyles on one side were dissected away, fixed, decalcified, dehydrated,
      embedded and sectioned. Safranin O staining was employed to identify variation in
      proteoglycan content, which in turn was used to predict patterns of articular
      cartilage stiffness in contralateral condylar specimens for each treatment group.
      Hematoxylin and eosin staining was used to quantify diet-induced changes in
      chondrocyte hypertrophy and cellularity. Mechanical tests document significant
      decreases in articular cartilage stiffness corresponding to patterns of
      extracellular matrix relative protein abundance in rabbits subjected to greater
      cyclical loading. This indicates that TMJs routinely subjected to higher
      masticatory stresses due to a challenging diet eventually develop postnatal
      decreases in the ability to counter compressive loads during postcanine biting
      and chewing. These findings provide novel information regarding TMJ performance,
      with broader implications about the costs and benefits of phenotypic plasticity
      as well as implications for how such biological processes affect connective
      tissue mechanobiology and pathobiology.

PMID- 29032865
TI  - Electron postmastectomy chest wall plus comprehensive nodal irradiation technique
      using Electron Monte Carlo dose algorithm.
AB  - For left-sided postmastectomy patients requiring chest wall plus comprehensive
      nodal irradiation, sometimes traditional techniques such as partial wide tangents
      or electron/tangents combination are not feasible due to abnormal chest wall
      contour or heart position or unusually wide excision scar. We developed electron
      chest wall irradiation technique using Electron Monte Carlo (EMC) dose algorithm
      that will achieve heart sparing with acceptable ipsilateral lung dose, minimal
      contralateral lung, and breast dose. Ten left-sided postmastectomy patients with
      very challenging anatomy were selected for this dosimetry study. The en face
      electron fields were designed from a single isocenter and gantry angle with
      different energy beams using different cutouts that matched on the skin. Smaller
      energy was used in the central thin chest wall part and higher energy in the
      medial internal mammary nodes (IMN) area, superior part of the thick chest wall,
      and/or axillary nodal area. The electron fields were matched to the photon
      supraclavicular field in the superior region. Daily field junctions were used to
      feather the match lines between all the fields. Electron field dose calculations
      were done with Monte Carlo. Five patients' chest wall fields were planned with
      6/9MeVcombination, 1 with 6/12 MeV, 2 with 9/12 MeV, 1 with 9/16 MeV, and 1 with
      6/9/12 MeV. Institutional criteria of prescription dose of 50 Gy for target
      volumes and normal tissue dose were met with this technique in spite of the
      challenging anatomy. Mean heart dose averaged 3.0 Gy +/- 0.8 Gy. For ipsilateral
      lung, V20Gy and V5Gy averaged 33.2% +/- 4.5% and 64.6% +/- 9.6%, respectively.
      For contralateral lung, V5Gy averaged 5.1% +/- 5.0%. For contralateral breast,
      V5Gy averaged 3.3% +/- 3.1%. The electron chest wall irradiation technique using
      EMC dose algorithm can provide adequate dose coverage to the chest wall, IMNs,
      and/or axillary nodes while achieving heart sparing with acceptable ipsilateral
      lung dose, minimal contralateral lung, and breast dose.

PMID- 29032866
TI  - HSP90 maintains boar spermatozoa motility and mitochondrial membrane potential
      during heat stress.
AB  - Heat Shock Proteins (HSP) is a family of proteins that protects cells from high
      temperatures. The present work aimed to elucidate the role that HSP90 exerts on
      boar sperm incubated under heat stress conditions on viability, total motility
      (TM), progressive motility (PM), acrosome status, mitochondrial membrane
      potential and plasma membrane lipid organization. Sperm were incubated in non
      capacitating conditions (Tyrode's basal medium or TBM) for 3, 8 and 24h or in
      capacitating conditions (Tyrode's complete medium or TCM) for 4h at 38.5 degrees
      C or 40 degrees C (Heat stress) in the presence or absence of 5 or 20MUM of 17
      AAG, a specific HSP90 inhibitor. Sperm viability was not affected by the presence
      of 17-AAG in any condition tested compared with its own control (at the same
      temperature and incubation time). In non-capacitating conditions TM (22.7+/-4.1
      vs. 1.9+/-1.1; % mean+/-SEM), PM (3.1+/-0.9 vs. 0) and high mitochondrial
      membrane potential (19.5+/-2.2 vs. 11.8+/-0.8) decreased significantly in sperm
      incubated at 40 degrees C for 24h in the presence of 20MUM 17-AAG (control vs.
      20MUM 17-AAG, respectively; p<0.05). In sperm incubated at 38.5 degrees C only a
      mild decrease in TM was observed (48.7+/-3.1 vs. 32.1+/-4.8; control vs. 20MUM 17
      AAG, respectively; p<0.05). However, under capacitating conditions none of the
      sperm parameters studied were affected by 17-AAG after 4h of incubation. These
      results demonstrate for the first time the role of HSP90 in the maintenance of
      boar sperm motility and mitochondrial membrane potential during prolonged heat
      stress in non-capacitating conditions.

PMID- 29032867
TI  - Adherence to topical treatment of glaucoma, risk and protective factors: A
      review.
AB  - INTRODUCTION: Glaucoma is a chronic asymptomatic disease, progressing to loss of
      vision. Elevated intraocular pressure is the only modifiable factor. Adherence to
      glaucoma treatment varies from 2-80%. OBJECTIVE: To evaluate factors associated
      with adherence to topical glaucoma treatment reported in the literature, and to
      identify protective factors and risk factors, as well as modifiable and non
      modifiable factors, in order to take them into account to perform interventions
      in adherence. MATERIALS AND METHODS: A bibliographic search of articles published
      in the last 8 years in databases such as Clinical Key, Cochrane (OVID), EBSCO,
      Lilacs, PubMed and Science Direct, of different observational studies that
      performed a measurement of the treatment of glaucoma and to identify associated
      factors. RESULTS: A total of 7 studies were selected that directly and indirectly
      measured adherence to glaucoma treatment. Different risk and protective factors
      for adherence to treatment were found. These showed that African-American race,
      poor education, low personal income, and high treatment costs, are strongly
      related to poor adherence to treatment. It was also found that educational
      interventions and a good patient- physician relationship impacted positively on
      adherence. CONCLUSION: The results found are a guide for risk and protective
      factors for adherence to treatment of glaucoma. It is cost effective to educate
      patients to positively impact adherence. By identifying such factors, attention
      can be focused on poor adherence patients.

PMID- 29032868
TI  - What Measures Improve Reduction of Intussusception in Pediatric Patients?

PMID- 29032869
TI  - SEP-1: A Sepsis Measure in Need of Resuscitation?

PMID- 29032870
TI  - Insurance Status and Access to Urgent Primary Care Follow-up After an Emergency
      Department Visit in 2016.
AB  - STUDY OBJECTIVE: We examine the availability of follow-up appointments for
      emergency department (ED) patients without established primary care by insurance
      and clinical condition. METHODS: We used "secret shopper" methodology, employing
      2 black men to telephone all 53 primary care practices in greater New Haven,
      posing as new patients discharged from the ED and requesting follow-up
      appointments. Each practice received 6 scripted calls from each caller during an
      8-month period, reflecting all possible scenarios based on 3 insurance types
      (Medicaid, state exchange, and commercial) and 2 conditions (hypertension and
      back pain). Primary outcome was the proportion of calls that obtained an
      appointment in 7 calendar days (7-day appointment rate). Secondary outcomes
      included overall appointment rate and appointment wait time. RESULTS: Among the
      total of 604 calls completed, the 7-day appointment rate was 30.7% (95%
      confidence interval [CI] 22.6% to 38.8%). Compared with commercial insurance,
      Medicaid calls had lower 7-day rate (25.5% versus 35.7%; difference 10.2%; 95% CI
      2.2% to 18.1%) and overall appointment rate (53.5% versus 77.8%; difference
      24.4%; 95% CI 13.4% to 35.4%). There was no significant difference between state
      exchange and commercial insurance calls in 7-day rate (30.9% versus 35.7%;
      difference 4.8%; 95% CI -3.1% to 12.6%) or overall appointment rate (73.4% versus
      77.8%; difference 4.4%; 95% CI -2.7% to 11.6%). Back pain, compared with
      hypertension, had lower 7-day appointment rate (27.6% versus 33.7%; difference
      6.1%; 95% CI 1.0% to 11.2%), but no significant difference in overall appointment
      rates (67.0% versus 69.4%; difference 2.4%; 95% CI -2.7% to 7.5%). CONCLUSION:
      For patients without established primary care, obtaining timely follow-up after
      acute care in the ED is difficult, particularly for Medicaid beneficiaries.

PMID- 29032871
TI  - Can a Negative High-Sensitivity Troponin Result Rapidly Rule Out Acute Myocardial
      Infarction?

PMID- 29032872
TI  - Assessing Bleeding Risk in Patients With Intentional Overdoses of Novel
      Antiplatelet and Anticoagulant Medications.
AB  - STUDY OBJECTIVE: In recent years, the use of novel anticoagulants and
      antiplatelet agents has become widespread. Little is known about the toxicity and
      bleeding risk of these agents after acute overdose. The primary objective of this
      study is to evaluate the relative risk of all bleeding and major bleeding in
      patients with acute overdose of novel antiplatelet and anticoagulant medications.
      METHODS: This study is a retrospective study of acute ingestion of apixaban,
      clopidogrel, ticlopidine, dabigatran, edoxaban, prasugrel, rivaroxaban, and
      ticagrelor reported to 7 poison control centers in 4 states during a 10-year
      span. The prevalence of bleeding for each agent was calculated, and hemorrhage
      was classified as trivial, minor, or major. RESULTS: A total of 322 acute
      overdoses were identified, with the majority of cases involving clopidogrel (260;
      80.7%). Hemorrhage occurred in 16 cases (4.9%), including 7 cases of clopidogrel,
      6 cases of rivaroxaban, 2 cases of dabigatran, and 1 case of apixaban. Most cases
      of hemorrhage were classified as major (n=9). Comparing the novel anticoagulants
      with the P2Y12 receptor inhibitors, the relative risk for any bleeding with novel
      anticoagulant was 6.68 (95% confidence interval 2.63 to 17.1); the relative risk
      of major bleeding was 18.1 (95% confidence interval 3.85 to 85.0). CONCLUSION:
      Acute overdose of novel anticoagulants or antiplatelet agents is associated with
      a small risk of significant hemorrhage. The risk is greater with the factor Xa
      inhibitors and direct thrombin inhibitors than with the P2Y12 receptor
      antagonists.

PMID- 29032873
TI  - Intrarater Reliability of Range of Motion Measurements of the Uninjured Wrist in
      Women After Distal Radius Fracture.
AB  - PURPOSE: To determine the intrarater reliability of serial wrist and forearm
      range of motion (ROM) measurements of the uninjured limb, by 1 evaluator using a
      standardized technique of measurement, in women who have sustained a distal
      radius fracture. METHODS: From December 2007 to December 2014, skeletally mature
      women who had sustained an isolated distal radius fracture routinely had
      sequential measurements of wrist extension and flexion as well as forearm
      supination and pronation in both their injured and their uninjured limbs, at a
      minimum of 3-week intervals. The senior author (G.H.F.J.) used a standardized
      technique of measurement of ROM throughout this period, and these data related to
      the uninjured wrist and forearm were retrospectively reviewed. RESULTS: Of 508
      women who had a distal radius fracture, 506 had the measurements made of the
      uninjured wrist and forearm on 2, 300 on 3, and 128 on 4 separate occasions. The
      average age of the women was 61 years, with a range from 16 to 94 years. The
      intraclass correlation coefficients between measurements over time for extension,
      flexion, and supination measurements were 0.71, 0.63, 0.68, respectively, and
      0.47 for pronation. The intraclass correlation coefficient varied according to
      patient age, but without specific progression in any age group for any ROM.
      Extension, flexion, and supination decreased significantly as age increased,
      whereas forearm pronation did not. CONCLUSIONS: Measurement of wrist and forearm
      motion of the uninjured limb can be reliably reproduced by a single rater, most
      so for extension, flexion, and supination, and less so for pronation. Interrater
      reliability assessment remains to be evaluated. CLINICAL RELEVANCE: Given the
      intrarater reliability of wrist and forearm motion measurement, the opposite
      (uninjured) wrist probably represents a useful reference metric for motion
      restoration for recovery from injury to the opposite limb.

PMID- 29032874
TI  - Rotational Corrective Osteotomy for Malunited Distal Diaphyseal Radius Fractures
      in Children and Adolescents.
AB  - PURPOSE: To report our method of computer-planned rotational corrective osteotomy
      for malunited distal diaphyseal radius fractures in children and adolescents
      using a custom jig and to review the results of 4 cases. METHODS: Four patients
      (mean age, 13 years; range, 11-16 years) underwent computer-planned rotational
      corrective osteotomy for malunited distal diaphyseal radius fracture using a
      custom jig. We retrospectively evaluated their radiographic and clinical data.
      RESULTS: In patients who had marked restriction of forearm supination before
      osteotomy, the mean arc of forearm supination improved from 5 degrees  before
      surgery to 79 degrees  after surgery. Angular deformity on x-ray, range of
      forearm rotation, and grip strength all improved after surgery. Mild and moderate
      pain reported by 1 and 2 patients, respectively, was resolved after surgery.
      CONCLUSIONS: Computer-planned rotational corrective osteotomy for malunited
      distal diaphyseal radius fracture in children and adolescents using a custom jig
      is a strategy that facilitates the surgical procedure by accurately correcting
      both rotational and angular deformities on 1 plane in a single procedure. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic V.

PMID- 29032875
TI  - Ventilator use by emergency medical services during 911 calls in the United
      States.
AB  - BACKGROUND: Emergency and transport ventilators use in the prehospital field is
      not well described. This study examines trends of ventilator use by EMS agencies
      during 911 calls in the United States and identifies factors associated with this
      use. METHODS: This retrospective study used four consecutive releases of the US
      National Emergency Medical Services Information System (NEMSIS) public research
      dataset (2011-2014) to describe scene EMS activations (911 calls) with and
      without reported ventilator use. RESULTS: Ventilator use was reported in 260,663
      out of 28,221,321 EMS 911 scene activations (0.9%). Patients with ventilator use
      were older (mean age 67+/-18years), nearly half were males (49.2%), mostly in
      urban areas (80.2%) and cared for by advanced life support (ALS) EMS services
      (89.5%). CPAP mode of ventilation was most common (71.6%). "Breathing problem"
      was the most common dispatch complaint for EMS activations with ventilator use
      (63.9%). Common provider impression categories included "respiratory distress"
      (72.5%), "cardiac rhythm disturbance" (4.6%), "altered level of consciousness"
      (4.3%) and "cardiac arrest"(4.0%). Ventilator use was consistently higher at the
      Specialty Care Transport (SCT) and Air Medical Transport (AMT) service levels and
      increased over the study period for both suburban and rural EMS activations.
      Significant factors for ventilator use included demographic characteristics, EMS
      agency type, specific complaints, provider's primary impressions and condition
      codes. CONCLUSIONS: Providers at different EMS levels use ventilators during 911
      scene calls in the US. Training of prehospital providers on ventilation
      technology is needed. The benefit and effectiveness of this intervention remain
      to be assessed.

PMID- 29032876
TI  - Clinical value of triage lactate in risk stratifying trauma patients using
      interval likelihood ratios.
AB  - : Emergency physicians face the challenge of rapidly identifying high-risk trauma
      patients. Lactate (LAC) is widely used as a surrogate of tissue hypoperfusion.
      However, clinically important values for LAC as a predictor of mortality are not
      well defined. OBJECTIVES: 1. To assess the value of triage LAC in predicting
      mortality after trauma. 2. To compute interval likelihood ratios (LR) for LAC.
      METHODS: Retrospective chart review of trauma patients with a significant injury
      mechanism that warranted labs at an urban trauma center. OUTCOME: In-hospital
      mortality. Data are presented as median and quartiles or percentages with 95%
      confidence intervals. Groups (lived vs. died) were compared with Man-Whitney-U or
      Fisher's-exact test. Multivariate analysis was used to measure the association of
      the independent variables and mortality. The interval likelihood ratios were
      calculated for all LAC observed values. RESULTS: 10,575 patients; median age: 38
      [25-57]; 69% male; 76% blunt; 1.1% [n=119] mortality. LAC was statistically
      different between groups in univariate (2.3 [1.6,3.0] vs 2.8 [1.6,4.8], p=0.008)
      and multivariate analyses (odds ratio: 1.14 [1.08-1.21], p=0.0001). Interval
      ratios for LR- ranged from 0.6-1.0. Increasing LAC increased LR+. However, LR+
      for LAC reached 5 with LAC>9mmol/L and passed 10 (moderate and conclusive
      increase in disease probability, respectively) with LAC>18mmol/L. CONCLUSIONS: In
      a cohort of trauma patients with a wide spectrum of characteristics triage LAC
      was statistically able to identify patients at high risk of mortality. However,
      clinically meaningful contribution to decision-making occurred only at LAC>9. LAC
      was not useful at excluding those with a low risk of mortality.

PMID- 29032877
TI  - Intraoperative instillation of ropivacaine during the placement of sub-muscular
      cosmetic breast implants: Is there a clinical benefit?
AB  - INTRODUCTION: The sub-muscular placement of cosmetic breast implants leads to
      substantial pain due to the muscular distention. The aim of this study was to
      assess the efficiency of intraoperative ropivacaine instillation to reduce
      postoperative pain the day after surgery. MATERIAL AND METHODS: We conducted a
      prospective, controlled, single-blinded study comparing the intraoperative
      instillation of 7.5mg of ropivacaine through Redon drains with the standard
      procedure in 72 patients undergoing sub-muscular cosmetic breast augmentation for
      the first time. RESULTS: Pain at the awakening on postoperative day 1 was 4.8 on
      a simple numeric pain scale in the treatment group and 5.1 in the control group
      (P>0.05). On postoperative day 3, pain at awakening was 3.7 in both groups
      (P>0.05), and on postoperative day 5, pain was 2.8 in the treatment group and 2.7
      in the control group (P>0.05). CONCLUSION: Local instillation of ropivacaine in
      the implant pocket during surgery did not decrease postoperative pain on day 1,
      day 3 and day 5. From now on, we are able to tell to patients that the
      postoperative pain after sub-muscular cosmetic breast implants surgery is about
      5/10 on postoperative day 1, 4/10 at day 3 and 3/10 at day 5. LEVEL OF EVIDENCE:
      Level II.

PMID- 29032878
TI  - The anterolateral thigh perforator flap in pharyngo-esophageal reconstruction.
AB  - Today's customary techniques for pharyngo-esophageal reconstruction are jejunum
      and radial forearm free flaps. In this type of reconstruction, the jejunum flap
      is considered as the reference, but when its harvesting is not possible, the
      radial forearm flap is used. Since perforator flaps have begun to be developed,
      the anterolateral thigh flap (ATF) has become increasingly prominent in pharyngo
      esophageal reconstruction. The aim of our study was to describe the use of the
      anterolateral perforator flap in pharyngo-esophageal reconstruction (indications,
      harvesting method, flap design) and to discuss its advantages and drawbacks as
      regards oral feeding and esophageal speech.

PMID- 29032879
TI  - Geant4 based Monte Carlo simulation for verifying the modified sum-peak method.
AB  - The modified sum-peak method can practically estimate radioactivity by using
      solely the peak and the sum peak count rate. In order to efficiently verify the
      method in various experimental conditions, a Geant4 based Monte Carlo simulation
      for a high-purity germanium detector system was applied. The energy spectra in
      the detector were simulated for a 60Co point source in various source to detector
      distances. The calculated radioactivity shows good agreement with the number of
      decays in the simulation.

PMID- 29032880
TI  - Comparison of 131I activity measurements at the NCBJ RC POLATOM and the ENEA
      INMRI linked to the BIPM SIR system.
AB  - A bilateral comparison between ENEA-INMRI (Italy) and NCBJ RC POLATOM (Poland) of
      131I-solution activity measurements was organized in the year 2015 and piloted by
      POLATOM, which provided the sources for the comparison. The 131I master solution
      was standardized independently at both institutes by using Liquid Scintillation
      Counting and ionization chamber techniques. The 131I master solution was then
      sent by POLATOM to the BIPM International Reference System (SIR). The comparison
      was registered as an EURAMET.RI(II)-K2.I-131 key comparison allowing the ENEA
      INMRI result to enter in the SIR database.

PMID- 29032881
TI  - Estimation of 134Cs activity by a new approximation referred to the sum-peak
      method via a well-type Ge detector.
AB  - The activity of a sample containing 134Cs and 137Cs was estimated by means of a
      new approximation referred to the sum-peak method using a well-type Ge detector.
      The contribution of 137Cs to the total count rate was estimated from its peak
      count rate, and subtracted from the total count rate. Then the total count rate
      originating from 134Cs was estimated. Finally, the new method was applied and the
      134Cs activity was estimated.

PMID- 29032882
TI  - Adapting a Computerized Medical Dictation System to Prepare Academic Papers in
      Radiology.
AB  - Everyday radiologists use dictation software to compose clinical reports of
      imaging findings. The dictation software is tailored for medical use and to the
      speech pattern of each radiologist. Over the past 10 years we have used dictation
      software to compose academic manuscripts, correspondence letters, and texts of
      educational exhibits. The advantages of using voice dictation is faster
      composition of manuscripts. However, use of such software requires preparation.
      The purpose of this article is to review the steps of adapting a clinical
      dictation software for dictating academic manuscripts and detail the advantages
      and limitations of this technique.

PMID- 29032883
TI  - Evaluating the accuracy of intraoperative frozen section during inguinal lymph
      node dissection in penile cancer.
AB  - INTRODUCTION: Inguinal lymph node dissection is an integral part in the
      management of invasive penile tumors with intraoperative assessment often aiding
      decision-making during dissection. In this study, we evaluate the diagnostic
      value of intraoperative frozen section (FS) and analyze clinicopathologic factors
      that affect its accuracy. MATERIAL AND METHODS: We, retrospectively, reviewed 84
      patients with squamous cell carcinoma of the penis who underwent inguinal lymph
      node dissection at our institution. Intraoperative FS from the superficial
      inguinal nodes was available in 65 patients and compared with correspondent
      permanent sections (pathologic node staging [pN]). Sensitivity and specificity
      were calculated and factors associated with a false negative event were analyzed
      using logistic regression. RESULTS: The total positive node rate was 60% (39/65).
      Of 39 pN+ cases, 10 (25.6%) had false-negative FS, whereas the remaining 29 were
      concordant intraoperatively. Sensitivity and specificity were 0.74 and 1,
      respectively. On univariable analysis, higher body mass index was associated with
      a false negative event although there was no association with age, receipt of
      neoadjuvant therapy, or clinical node stage. CONCLUSION: Intraoperative FS is
      highly specific and moderately sensitive for the detection of positive
      superficial inguinal lymph nodes in penile cancer. Its use can help guide
      intraoperative surgical planning while limiting its reliance for patients with
      higher body mass index.

PMID- 29032884
TI  - The genetics underlying idiopathic ventricular fibrillation: A special role for
      catecholaminergic polymorphic ventricular tachycardia?
AB  - BACKGROUND: Ventricular fibrillation (VF) is a major cause of sudden cardiac
      death. In some cases clinical investigations fail to identify the underlying
      cause and the event is classified as idiopathic (IVF). Since mutations in
      arrhythmia-associated genes frequently determine arrhythmia susceptibility,
      screening for disease-predisposing variants could improve IVF diagnostics.
      METHODS AND RESULTS: The study included 76 Finnish and Italian patients with a
      mean age of 31.2years at the time of the VF event, collected between the years
      1996-2016 and diagnosed with idiopathic, out-of-hospital VF. Using whole-exome
      sequencing (WES) and next-generation sequencing (NGS) approaches, we aimed to
      identify genetic variants potentially contributing to the life-threatening
      arrhythmias of these patients. Combining the results from the two study
      populations, we identified pathogenic or likely pathogenic variants residing in
      the RYR2, CACNA1C and DSP genes in 7 patients (9%). Most of them (5, 71%) were
      found in the RYR2 gene, associated with catecholaminergic polymorphic ventricular
      tachycardia (CPVT). These genetic findings prompted clinical investigations
      leading to disease reclassification. Additionally, in 9 patients (11.8%) we
      detected 10 novel or extremely rare (MAF<0.005%) variants that were classified as
      of unknown significance (VUS). CONCLUSION: The results of our study suggest that
      a subset of patients originally diagnosed with IVF may carry clinically-relevant
      variants in genes associated with cardiac channelopathies and cardiomyopathies.
      Although misclassification of other cardiac channelopathies as IVF appears rare,
      our findings indicate that the possibility of CPVT as the underlying disease
      entity should be carefully evaluated in IVF patients.

PMID- 29032885
TI  - The "Subtle" connection between development of cardiac implantable electrical
      device infection and survival after complete system removal: An observational
      prospective multicenter study.
AB  - BACKGROUND: Despite the improvements in transvenous lead extraction (TLE),
      patients with cardiac implantable device related infection (CIEDI) have a poor
      prognosis at long term. We explored the possible role of factors associated with
      development of CIEDI as predictors of post-TLE survival. METHODS: We performed a
      multi-center prospective observational study in a population of consecutive
      patients referred for TLE for CIEDI. We adopted a previously developed 10-point
      scale for CIEDI risk stratification and assessed its performance in predicting
      post-TLE survival. RESULTS: We enrolled 169 consecutive patients with CIEDI
      (systemic infection in 48.5% and vegetations in 24.5%). A Shariff score >=3 was
      present in 102/169 (60.4%) of the enrolled patients. Complete radiological
      success of TLE was obtained in 163 patients. Twenty-seven patients (15.9%) died
      after a mean follow-up of 20.8+/-12.0months. Two factors were independently
      associated with post-TLE death: a Shariff score >=3 (HR 10.833, 95% CI 2.544
      46.129; p=0.001) and the presence of vegetations at transesophageal
      echocardiography (HR 3.324, 95% CI 1.530-7.221; p=0.002). CONCLUSIONS: Risk
      factors for development of CIEDI are also predictive of post TLE mortality,
      together with the presence of vegetations. Improvement of our preventive
      strategies for CIEDI is crucial for enhancing the outcomes of CIED patients
      overall.

PMID- 29032886
TI  - Prevalence and Risk Factors for Paroxysmal Atrial Fibrillation and Flutter
      Detection after Cryptogenic Ischemic Stroke.
AB  - INTRODUCTION: Long-term cardiac monitoring with implantable loop recorders (ILRs)
      has revealed occult paroxysmal atrial fibrillation and flutter (PAF) in a
      substantial minority of cryptogenic ischemic stroke (CIS) patients. Herein, we
      aim to define the prevalence, clinical relevance, and risk factors for PAF
      detection following early poststroke ILR implantation. MATERIALS AND METHODS: A
      retrospective study of CIS patients (n = 100, mean age 65.8 years; 52.5% female)
      who underwent ILR insertion during, or soon after, index stroke admission.
      Patients were prospectively followed by the study cardiac electrophysiologist who
      confirmed the PAF diagnosis. Univariate and multivariate analyses compared
      clinical, laboratory, cardiac, and imaging variables between PAF patients and non
      PAF patients. RESULTS: PAF was detected in 31 of 100 (31%) CIS patients, and
      anticoagulation was initiated in almost all (30 of 31, 96.8%). Factors associated
      with PAF detection include older age (mean [year] 72.9 versus 62.9; P = .003),
      white race (odds ratio [OR], 4.5; confidence interval [CI], 1.8-10.8; P = .001),
      prolonged PR interval (PR > 175 ms; OR, 3.3; CI, 1.2-9.4; P = .022), larger left
      atrial (LA) diameter (mean [cm] 3.7 versus 3.5; P = .044) and LA volume index
      (mean [cc/m2]; 30.6 versus 24.2; P = .014), and lower hemoglobin (Hb)A1c (mean
      [%] 6.0 versus 6.4; P = .036). Controlling for age, obesity (body mass index > 30
      kg/m2; OR, 1.2; CI, 1.1-1.4; P = .033) was independently associated with PAF
      detection. DISCUSSION: PAF was detected with high prevalence following early
      postcryptogenic stroke ILR implantation and resulted in significant management
      changes. Older age, increased PR interval, LA enlargement, and lower HbA1c are
      significantly associated with PAF detection. Controlling for age, obesity is an
      independent risk factor. A larger prospective study is warranted to confirm these
      findings.

PMID- 29032887
TI  - Virtual Simulation in Enhancing Procedural Training for Fluoroscopy-guided Lumbar
      Puncture: A Pilot Study.
AB  - RATIONALE AND OBJECTIVES: Fluoroscopy-guided lumbar puncture (FGLP) is a basic
      procedural component of radiology residency and neuroradiology fellowship
      training. Performance of the procedure with limited experience is associated with
      increased patient discomfort as well as increased radiation dose, puncture
      attempts, and complication rate. Simulation in health care is a developing field
      that has potential for enhancing procedural training. We demonstrate the design
      and utility of a virtual reality simulator for performing FGLP. MATERIALS AND
      METHODS: An FGLP module was developed on an ImmersiveTouch platform, which
      digitally reproduces the procedural environment with a hologram-like projection.
      From computed tomography datasets of healthy adult spines, we constructed a 3-D
      model of the lumbar spine and overlying soft tissues. We assigned different
      physical characteristics to each tissue type, which the user can experience
      through haptic feedback while advancing a virtual spinal needle. Virtual
      fluoroscopy as well as 3-D images can be obtained for procedural planning and
      guidance. The number of puncture attempts, the distance to the target, the number
      of fluoroscopic shots, and the approximate radiation dose can be calculated.
      Preliminary data from users who participated in the simulation were obtained in a
      postsimulation survey. RESULTS: All users found the simulation to be a realistic
      replication of the anatomy and procedure and would recommend to a colleague. On a
      scale of 1-5 (lowest to highest) rating the virtual simulator training overall,
      the mean score was 4.3 (range 3-5). CONCLUSIONS: We describe the design of a
      virtual reality simulator for performing FGLP and present the initial experience
      with this new technique.

PMID- 29032888
TI  - Calcium channel blockers for lung function improvement in asthma: A systematic
      review and meta-analysis.
AB  - BACKGROUND: For decades, calcium channel blockers (CCBs) have been believed to
      play a role in asthma treatment. However, the clinical efficacy of CCBs for lung
      function improvement in patients with asthma has not been qualitatively
      evaluated. OBJECTIVE: To assess the effect of CCBs vs placebo on lung function
      test results in adults with asthma. METHODS: Various databases were
      systematically searched to identify all randomized clinical trials with adults
      with asthma. We aimed to assess the influence of CCBs on forced expiratory volume
      in 1 second (FEV1), forced vital capacity (FVC), peak expiratory flow rate
      (PEFR), and provocative concentration of bronchoconstrictive agents causing a 20%
      decrease in FEV1 (PC20) compared with a placebo. All effect estimates were pooled
      by the generic inverse variance method with random-effects meta-analysis.
      Subgroup analysis, sensitivity analysis, and heterogeneity investigation were
      performed. RESULTS: Thirty eligible articles with 301 patients were included in
      this meta-analysis. Our results revealed that in a standard exercise test CCBs
      could produce a mean maximal percentage decrease in FEV1 of 11.56% (95%
      confidence interval, 8.97%-14.16%; P < .001) and an increase in postdose FEV1 by
      80 mL (95% confidence interval, 0.02-0.15 mL; P = .01). However, there was no
      statistical significance for CCBs in postdose FVC, PEFR, or PC20 of histamine and
      methacholine. CONCLUSION: CCBs may be beneficial for lung function improvement in
      asthma, especially in exercise-induced asthma. However, there is a lack of
      evidence for CCBs protecting asthma patients from chemical irritation.

PMID- 29032889
TI  - Melting Ice and Boiling Water in the Mountains: A History and Physics Essay.

PMID- 29032890
TI  - [Identification of health outcome indicators in Primary Care. A review of
      systematic reviews].
AB  - INTRODUCTION: Outcome measures are being widely used by health services to assess
      the quality of health care. It is important to have a battery of useful
      performance indicators with high validity and feasibility. Thus, the objective of
      this study is to perform a review of reviews in order to identify outcome
      indicators for use in Primary Care. METHODOLOGY: A review of systematic reviews
      (umbrella review) was carried out. The following databases were consulted:
      MedLine, EMBASE, and CINAHL, using descriptors and free terms, limiting searches
      to documents published in English or Spanish. In addition, a search was made for
      free terms in different web pages. Those reviews that offered indicators that
      could be used in the Primary Care environment were included. RESULTS: This review
      included a total of 5 reviews on performance indicators in Primary Care, which
      consisted of indicators in the following areas or clinical care processes: in
      osteoarthritis, chronicity, childhood asthma, clinical effectiveness, and
      prescription safety indicators. A total of 69 performance indicators were
      identified, with the percentage of performance indicators ranging from 0% to
      92.8%. None of the reviews identified performed an analysis of the measurement
      control (feasibility or sensitivity to change of indicators). CONCLUSIONS: This
      paper offers a set of 69 performance indicators that have been identified and
      subsequently validated and prioritised by a panel of experts.

PMID- 29032893
TI  - Nystagmus due to ranitidine.

PMID- 29032892
TI  - Evaluation and management of skeletal disease in cancer care.
AB  - Recently, there have been considerable advancements in cancer therapies thereby
      prolonging the life of cancer survivors. However, these recent advancements
      present new challenges in the management of bone disease in cancer survivors.
      Bone acts as a fertile soil for cancer seeding and bone health is often
      compromised because of increased inflammatory cytokines in cancer, direct cancer
      metastasis and toxic effects of anti-cancer therapies. This effect is more
      pronounced in elderly population who already have compromised bone mineral
      density leading to increased skeletal related events and bone pain. Timely
      diagnosis and effective interventions are essential for reducing bone-related
      morbidity in cancer survivors. Also, a complex interdependence exists between
      cancer related bone disease and tumor growth, creating a vicious circle of
      extensive bone destruction and cancer progression. Hence, maintenance of bone
      health and integrity plays a pivotal role in comprehensive cancer care. The bone
      targeted treatments have been shown to preserve bone health, and modify the
      course of the underlying cancer. Management of long-term bone health requires a
      broad knowledge base that endocrinologists, oncologists and other care team
      members should be aware of. The manuscript highlights the skeletal effects of
      cancer, adjuvant therapies used for hormone-responsive cancers, chemotherapy
      induced bone loss and steps for accurate diagnosis and management of bone disease
      in cancer survivors by bridging the gaps in the comprehensive cancer care.

PMID- 29032895
TI  - Cardiac sympathetic denervation predicts PD in at-risk individuals.
AB  - INTRODUCTION: By the time a person develops the motor manifestations of
      Parkinson's disease (PD), substantial loss of nigrostriatal dopamine neurons has
      already occurred. There is great interest in identifying biomarkers that can
      detect pre-clinical PD. Braak's neuropathological staging concept imputes early
      autonomic involvement. Here we report results from a small prospective cohort
      study about the utility of neuroimaging evidence of cardiac sympathetic
      denervation in predicting PD among individuals with multiple PD risk factors.
      METHODS: Subjects provided information about family history of PD, olfactory
      dysfunction, dream enactment behavior, and orthostatic hypotension at a protocol
      specific website. From this pool, 27 people with at least 3 risk factors
      confirmed underwent cardiac 18F-dopamine positron emission tomographic scanning
      and were followed for at least 3 years. Interventricular septal and left
      ventricular free wall concentrations of 18F-dopamine-derived radioactivity were
      measured. RESULTS: Of the 27 subjects, 4 were diagnosed with PD within the 3-year
      follow-up period (Pre-Clinical PD group); 23 risk-matched (mean 3.2 risk factors)
      subjects remained disease-free (No-PD group). Compared to the No-PD group, the
      Pre-Clinical PD group had lower initial values for septal and free wall
      concentrations of 18F-dopamine-derived radioactivity (p = 0.0248, 0.0129). All 4
      Pre-Clinical PD subjects had evidence of decreased cardiac sympathetic
      innervation in the interventricular septum or left ventricular free wall, in
      contrast with 3 of 23 (13%) No-PD subjects (p = 0.0020 by Fisher's exact test).
      CONCLUSION: People with multiple PD risk factors and diagnosed with PD within 3
      years have evidence of antecedent cardiac sympathetic denervation. The findings
      fit with Braak's staging concept.

PMID- 29032896
TI  - Risk factors of ICU or high dependency requirements amongst hospitalized
      pediatric pertussis cases: A 10 year retrospective series, Singapore.
AB  - INTRODUCTION: Pertussis causes the highest complication rates and deaths in the
      infant group. Our study explored risk factors for ICU/high dependency (HD)
      admissions and intubation/non-invasive ventilation (NIV). METHODS: A
      retrospective review of pertussis admissions over 10 years from 2007 to 2016 was
      done at KK Women's and Children's Hospital, Singapore. To understand risk factors
      for severe pertussis infection, we compared cases requiring ICU/HD care with
      controls admitted to the general ward. Risk factors for intubation/NIV were also
      studied. Vaccine efficacy for protection against ICU/HD admission or
      intubation/NIV was also calculated. RESULTS: There were 200 pertussis patients
      with a median age of 2.75 months. Sixty-one % were <=3 months and 14.5% were <6
      weeks old. Majority of patients (77%) had no prior pertussis vaccination. After
      removing 3 patients with missing vaccination records, 20 cases were compared with
      177 controls. On univariate analysis, risk factors for ICU/HD admission
      comprised: Age <=3 months, contact history, underlying co-morbidity, prematurity,
      absent DTaP vaccination, lymphocytosis, hyperleukocytosis (wbc >=50*109/L),
      thrombocytosis (platelet >=500*109/L), and pneumonia. Multivariate analysis
      revealed that age <=3 months (OR 40, 95% CI 4.57-1111.11, p=.007), co-morbidity
      (OR 8.46 (95% CI 1.47-56.89, p=.019), pneumonia (OR 18.08, 95% CI 3.22-132.15,
      p=.002), white cell count (OR 1.07, 95% CI 1.01-1.14, p=.023) and cyanosis (OR
      5.09, 95% CI 1.31-24.71, p=.026) were risk factors for ICU/HD admission. Prior
      DTaP vaccination had a vaccine effectiveness of 86.5% in preventing ICU/HD
      admission and 82.1% in preventing intubation/NIV. CONCLUSIONS: As the majority of
      pertussis patients were infants <=3 months old who are at high risk for ICU/HD
      admission and intubation/NIV, prevention is key to reducing pertussis morbidity.
      Even though not statistically significant, DTaP vaccination had a role in
      preventing ICU/HD admission and intubation/NIV.

PMID- 29032894
TI  - Atypical PKC, PKClambda/iota, activates beta-secretase and increases Abeta1-40/42
      and phospho-tau in mouse brain and isolated neuronal cells, and may link
      hyperinsulinemia and other aPKC activators to development of pathological and
      memory abnormalities in Alzheimer's disease.
AB  - Hyperinsulinemia activates brain Akt and PKC-lambda/iota and increases Abeta1
      40/42 and phospho-tau in insulin-resistant animals. Here, we examined underlying
      mechanisms in mice, neuronal cells, and mouse hippocampal slices. Like Abeta1
      40/42, beta-secretase activity was increased in insulin-resistant mice and
      monkeys. In insulin-resistant mice, inhibition of hepatic PKC-lambda/iota
      sufficient to correct hepatic abnormalities and hyperinsulinemia simultaneously
      reversed increases in Akt, atypical protein kinase C (aPKC), beta-secretase, and
      Abeta1-40/42, and restored acute Akt activation. However, 2 aPKC inhibitors
      additionally blocked insulin's ability to activate brain PKC-lambda/iota and
      thereby increase beta-secretase and Abeta1-40/42. Furthermore, direct blockade of
      brain aPKC simultaneously corrected an impairment in novel object recognition in
      high-fat-fed insulin-resistant mice. In neuronal cells and/or mouse hippocampal
      slices, PKC-iota/lambda activation by insulin, metformin, or expression of
      constitutive PKC-iota provoked increases in beta-secretase, Abeta1-40/42, and
      phospho-thr-231-tau that were blocked by various PKC-lambda/iota inhibitors, but
      not by an Akt inhibitor. PKC-lambda/iota provokes increases in brain beta
      secretase, Abeta1-40/42, and phospho-thr-231-tau. Excessive signaling via PKC
      lambda/iota may link hyperinsulinemia and other PKC-lambda/iota activators to
      pathological and functional abnormalities in Alzheimer's disease.

PMID- 29032898
TI  - Estimating influenza vaccine effectiveness: Evolution of methods to better
      understand effects of confounding in older adults.
AB  - Older adults are at high risk for serious complications of influenza illness and
      loss of vaccine-mediated protection. It is increasingly recognized that in
      addition to age, multiple chronic conditions and associated frailty contribute to
      the decline in vaccine effectiveness in this population. However, observational
      studies have been fraught with issues of confounding related to the degree of
      frailty and functional decline, measures of which are not included in standard
      administrative health care databases that are used to calculate vaccine
      effectiveness. This issue has led to the identification of confounding by
      indication or from "healthy vaccinee" bias, which respectively lead to
      underestimates or overestimates of influenza vaccine effectiveness. In addition,
      the sensitivity and specificity of the criteria used to define influenza-like
      illness declines with increasing age due to atypical presentations of illness and
      the inability to distinguish between influenza and other respiratory viruses. The
      test-negative case:control design has emerged as a method to estimate influenza
      vaccine effectiveness by comparing vaccination rates in those with laboratory
      confirmed influenza to those with other acute viral respiratory illnesses. This
      review provides a perspective on how test-negative case:control study designs and
      new insights into mechanisms of protection have considerably strengthened
      influenza vaccination policy decisions for older adults that have historically
      been undermined by the conclusions of observational studies.

PMID- 29032891
TI  - Modulating the immune system through nanotechnology.
AB  - Nowadays, nanotechnology-based modulation of the immune system is presented as a
      cutting-edge strategy, which may lead to significant improvements in the
      treatment of severe diseases. In particular, efforts have been focused on the
      development of nanotechnology-based vaccines, which could be used for
      immunization or generation of tolerance. In this review, we highlight how
      different immune responses can be elicited by tuning nanosystems properties. In
      addition, we discuss specific formulation approaches designed for the development
      of anti-infectious and anti-autoimmune vaccines, as well as those intended to
      prevent the formation of antibodies against biologicals.

PMID- 29032897
TI  - Prevnar-13 vaccine failure in a mouse model for vitamin A deficiency.
AB  - Streptococcus pneumoniae (pneumococcus) is responsible for serious pediatric
      respiratory infections, and kills close to one million children under the age of
      five each year. Unfortunately, the Prevnar-13 vaccine (PCV-13) that is used to
      protect children from the serious consequences of pneumococcus infections is not
      always successful. Given that vitamin A deficiency (VAD) is known to affect
      children in both developed and developing countries, we asked if VAD could be
      responsible, at least in part, for PCV-13 vaccine failures. In a mouse model for
      VAD, we found that PCV-13 failed to elicit binding and neutralizing antibody
      activities. Unlike vaccinated, vitamin-replete animals, vaccinated VAD animals
      were not protected from lethal pneumococcus infections. Results suggest that
      children with VAD may be susceptible to serious pneumococcal infections even
      after having received the PCV-13 vaccine.

PMID- 29032899
TI  - Th1 epitope peptides induce protective immunity against Rickettsia rickettsii
      infection in C3H/HeN mice.
AB  - Rickettsia rickettsii is the causative pathogen of Rocky Mountain spotted fever
      (RMSF). Adr2, YbgF and OmpB are protective antigens of R. rickettsii. In this
      study, 90 candidate peptides were selected from these antigens based on their
      high-affinity binding capacity for the MHC class II molecule H2 I-A or H2 I-E
      using bioinformatic methods. Six peptides were determined using ELISPOT assay to
      be immunodominant based on the IFN-gamma recall responses of CD4+ T cells from
      mice immunized with R. rickettsii. Six nucleotide sequences encoding the
      immunodominant peptides were linked in series and inserted into a plasmid for
      expression in Escherichia coli cells, resulting in a new, recombinant polypeptide
      termed GWP. After immunization and challenge, the rickettsial load or
      histopathological lesions in the organs of mice immunized with GWP or pooled
      peptides was significantly lower than that in organs of mice immunized with PBS
      or the individual peptide OmpB399. An in vitro neutralization test revealed that
      sera from mice immunized with GWP, OmpB399, or pooled peptides reduced R.
      rickettsii adherence to, and invasion of, vascular endothelial cells.
      Furthermore, significantly higher levels of IgG, IgG1, or IgG2a were detected in
      sera from mice immunized with GWP or pooled peptides, and significantly higher
      levels of IFN-gamma or TNF-alpha secreted by CD4+ T cells from R. rickettsii
      infected mice were detected after immunization with GWP. Altogether, our results
      indicated that polypeptides, especially GWP, could induce a Th1-type immune
      response against R. rickettsii infection, which might contribute to the rational
      design of peptide-based vaccines for RMSF.

PMID- 29032900
TI  - In Silico Vaccine Strain Prediction for Human Influenza Viruses.
AB  - Vaccines preventing seasonal influenza infections save many lives every year;
      however, due to rapid viral evolution, they have to be updated frequently to
      remain effective. To identify appropriate vaccine strains, the World Health
      Organization (WHO) operates a global program that continually generates and
      interprets surveillance data. Over the past decade, sophisticated computational
      techniques, drawing from multiple theoretical disciplines, have been developed
      that predict viral lineages rising to predominance, assess their suitability as
      vaccine strains, link genetic to antigenic alterations, as well as integrate and
      visualize genetic, epidemiological, structural, and antigenic data. These could
      form the basis of an objective and reproducible vaccine strain-selection
      procedure utilizing the complex, large-scale data types from surveillance. To
      this end, computational techniques should already be incorporated into the
      vaccine-selection process in an independent, parallel track, and their
      performance continuously evaluated.

PMID- 29032902
TI  - Should We Have a Better Definition of Pseudoparalysis in Patients With Rotator
      Cuff Tears?
AB  - Pseudoparalysis has been previously described as the inability to elevate the arm
      over 90 degrees  in the setting of a rotator cuff tear. Controversy exists
      regarding the optimal treatment for patients with a pseudoparalytic shoulder with
      a rotator cuff tear with options including rotator cuff repair and reverse
      shoulder arthroplasty. Recent literature suggests that pseudoparalysis can
      reliably be corrected with a rotator cuff repair and is more cost effective than
      reverse shoulder arthroplasty. We believe that the arbitrary cutoff of 90 degrees
      is too generous and leads to confusion. We believe that the definition of
      pseudoparalysis needs to be refined to clarify indications for treatment and not
      base a decision on a simple measurement without other factors considered. We
      suggest that pseudoparalysis as a description should include elevation limited to
      up to 45 degrees . The patient should also be described as having a chronic and
      essentially atraumatic onset of symptoms and the rotator cuff tear is massive
      with at least grade II to III fatty infiltration. Only with increasing precision
      and describing the actual patient situation and limitations will we be more able
      to correctly compare treatment alternatives.

PMID- 29032901
TI  - Bosworth and modified Phemister techniques revisited. A comparison of
      intraarticular vs extraarticular fixation methods in the treatment of acute
      Rockwood type III acromioclavicular dislocations.
AB  - OBJECTIVE: The aim of this study was to compare the long-term clinical and
      radiological results of Acromioclavicular (AC) fixation with K-wires (the
      modified Phemister procedure) and Coracoclavicular (CC) fixation with the
      Bosworth screw in the surgical treatment of Type 3 AC joint dislocations.
      METHODS: Thirty-two patients with complete set of medical records and who
      received surgical treatment between September 2005 and January 2009 due to acute
      Rockwood Type 3 AC joint dislocation and properly attended their follow-ups were
      retrospectively evaluated. Sixteen patients (13 males, 3 females; mean age: 38,
      range: 24-52 years) were treated with CC fixation with Bosworth screw (Group 1),
      and the other 16 (12 males, 4 females; mean age: 53.3, range: 38-64 years) with
      AC fixation using K-wires (Group 2). RESULTS: The mean follow-up time was 96
      months for Group 1 and 93 months for Group 2 patients (p > 0.05). The mean
      Constant-Murley score at the final follow-up was 84.7 in Group 1 and 87.3 in
      Group 2 (p = 0.069). Radiological evaluation of the patients revealed AC
      arthrosis in 2 and 3 patients in Group 1 and 2, respectively. In Group 2, one
      patient had a recurrent dislocation, three patients had AC arthrosis and two
      patients had ossification in the CC ligament (Fig. 2). There was no superficial
      or deep wound infection in Group 1, while two patients from Group 2 had a
      superficial wound infection. CONCLUSIONS: Our results suggest that both
      techniques are reliable and provide adequate reduction and similar outcomes in
      terms of functionality and pain levels, following the reduction of Type 3 AC
      joint dislocations. With lower rates of wound site infection in the early and AC
      arthrosis in the late postoperative period, CC fixation method with the Bosworth
      screw may be a better surgical option than AC fixation method with K-wires. LEVEL
      OF EVIDENCE: Level III, Therapeutic study.

PMID- 29032903
TI  - Single-Shot Femoral Nerve Block Does Not Cause Long-Term Strength and Functional
      Deficits Following Anterior Cruciate Ligament Reconstruction.
AB  - PURPOSE: To determine if patients treated with a single-shot femoral nerve block
      have strength and functional deficits at 9-month follow-up. METHODS: Forty-three
      patients who underwent primary anterior cruciate ligament reconstructions were
      randomized to receive either a preoperative single-shot femoral nerve block or
      local infiltration anesthesia for primary pain control. All patients underwent a
      standardized comprehensive rehabilitation program postoperatively. Isokinetic
      strength and function was tested using a Biodex machine at 9 months or more
      postoperatively comparing the operative and nonoperative extremity. RESULTS: No
      significant difference in strength was found at an average of 10.6 months
      postoperatively (range, 9-15 months) between the femoral nerve block and control
      groups. In comparing strength deficits, we found no difference in slow isokinetic
      extension strength (22.4% vs 27.8%, P = .51), fast isokinetic extension strength
      (18.5% vs 12.5%, P = .41), slow isokinetic flexion strength (11.0% vs 15.1%, P =
      .55), and fast isokinetic flexion strength (8.2% vs 4.9%, P = .56) in the femoral
      nerve block versus control groups, respectively. In terms of functional outcomes,
      there also was no difference in deficits for single-leg hop distance (P = .12),
      timed single-leg hop (P = .74), and single-leg triple hop distance (P = .94).
      Maximal strength noted to be within 15% of the contralateral limb was achieved in
      40% of patients and maximal function in 63% of patients at an average of 10.6
      months postoperatively. A 13% complication rate was found in patients who
      received a femoral nerve block (1 with prolonged quadriceps inhibition and 2 with
      prolonged sensory disturbances). CONCLUSIONS: Our study found a 13% motor/sensory
      complication rate in patients who underwent femoral nerve block for pain control
      after anterior cruciate ligament reconstruction. Although these deficits may
      persist, they are not permanent and are not different when compared with controls
      at 9-month follow-up. However, maximal strength and function are not fully
      restored at normal return to play time and rehabilitation should continue long
      term to maximize recovery. LEVEL OF EVIDENCE: Level I, prospective randomized
      trial.

PMID- 29032904
TI  - Endovascular aortic sealing with Nellix reduces intraoperative radiation dose
      when compared to endovascular aortic repair.
AB  - OBJECTIVE: To analyze radiation exposure during endovascular aortic sealing
      (EVAS) in comparison with standard endovascular aortic repair (EVAR) in clinical
      practice. METHODS: From December 2013 to October 2016 (35 months), 60 patients
      were analyzed for intraoperative radiation exposure during EVAR: 30 consecutive
      patients (mean age, 73.10 years; 28 male) received EVAS (Nellix Endologix);
      within the same time frame, 30 patients were treated with standard EVAR (mean
      age, 71.87 years; 30 male). An indirect dose analysis was performed for both
      groups of patients, including effective dose and cumulative air kerma.
      Furthermore, fluoroscopy time (FT), dose area product, and time of procedure were
      included in the study. RESULTS: The effective dose was significantly reduced in
      the EVAS group (3.72 mSv) compared with the group treated with standard EVAR (6.8
      mSv; P <= .001). The cumulative air kerma was also lowered in EVAS (67.65 mGy vs
      139 mGy in EVAR; P <= .001). FT for the entire group was 13 minutes and was
      shorter (P < .001) for EVAS (9 minutes) in comparison with EVAR (19 minutes). The
      dose area product for the entire cohort was 16.95 Gy.cm2 and was lower during
      EVAS (12.4 Gy.cm2) than during EVAR (22.6 Gy.cm2; P < .001). The median operating
      time for the entire group was 123.5 minutes and was significantly shorter (P <
      .01) for EVAS (119 minutes vs EVAR at 132 minutes). The FT shows a significant
      correlation with the patient's weight (P = .022), body mass index (P = .004), and
      time of procedure (P = .005). CONCLUSIONS: EVAS is associated with a relevant
      decrease in indirect measured radiation dose and time of procedure compared with
      standard EVAR. A relevant reduction in dose during EVAS is highly likely to
      result in lower exposure to radiation for physicians and staff. Such a result
      would be highly advantageous and calls for further analysis.

PMID- 29032905
TI  - Analysis of wound healing time and wound-free period as outcomes after surgical
      and endovascular revascularization for critical lower limb ischemia.
AB  - BACKGROUND: Traditional end points, such as amputation-free survival, used to
      assess the clinical effectiveness of lower limb revascularization have
      shortcomings because they do not account independently for wound nonhealing and
      recurrence or patient survival. Wound healing process and maintenance of a wound
      free state after revascularization were not well-studied. The aim of this study
      was to elucidate the long-term clinical course of ischemic wounds after
      revascularization. We focused on initial wound healing process as well as the
      maintenance of a wound-free state after achievement of wound healing. We
      introduced a wound-free period (WFP; the period during which limbs maintained an
      ulcer-free state) and Wound Recurrence and Amputation-free Survival (WRAFS) as
      parameters and tested their effectiveness in evaluating clinical outcomes of
      limbs treated using endovascular therapy (EVT) and surgical revascularization.
      METHODS: The medical records of patients developing lower critical limb ischemia
      with tissue loss who underwent surgical or endovascular revascularization of the
      infrainguinal vessels between 2009 and 2013 were reviewed retrospectively. The
      risk factors for achieving wound healing and WRAFS were analyzed using Kaplan
      Meier survival curves and Cox regression model. Risk factors to prolong wound
      healing time (WHT) and reduce WFP were determined by the least squares method.
      RESULTS: In total, 233 patients underwent 278 limb revascularizations; 138
      endovascular and 140 surgical procedures were performed as first treatments. The
      proportion of healed wounds 1, 2, and 3 years after primary revascularization was
      64.0%, 69.7%, and 70.5%, respectively. Significant risk factors for wound healing
      were an EVT-first strategy (risk ratio [RR], 2.47), congestive heart failure (RR,
      2.05), and wound, ischemia, and foot infection wound grade (RR, 1.59). The mean
      WHT was 143.7 days. An EVT-first strategy and wound infection contributed to
      significantly longer WHT. The mean WFP was 711.0 days. An EVT-first strategy,
      history of coronary artery disease, and dialysis dependence were associated with
      significantly shorter WFPs. WRAFS at 1 and 2 years after achievement of wound
      healing were 76.9% and 64.2%, respectively. Significant risk factors against
      WRAFS were a history of coronary artery disease (RR, 1.68), dialysis dependence
      (RR, 2.03), and being wheel chair bound (RR, 1.64). CONCLUSIONS: EVT
      revascularization was associated with longer WHT, reduced wound healing rate, and
      a shorter WFP compared with surgical revascularization. wound, ischemia, and foot
      infection grade was associated with longer WHT and reduced wound healing rate,
      but not associated with a shorter WFP. Systemic conditions such as dialysis
      dependence, congestive heart failure, and being wheel chair bound were associated
      with reduced wound healing rate and shorter WFP, presumably because they limited
      life expectancy. WHT and WFP are useful criteria for evaluating limb outcomes in
      patients with critical limb ischemia.

PMID- 29032906
TI  - Live-dead discrimination analysis, qPCR assessment for opportunistic pathogens,
      and population analysis at ozone wastewater treatment plants.
AB  - In respect to direct and indirect water reuse, the microbiological quality of
      treated wastewater is highly important. Conventional wastewater treatment plants
      are normally not equipped with advanced technologies for the elimination of
      bacteria. Molecular biology analyses were combined with live-dead discrimination
      analysis of wastewater population using Propidium monoazide (PMA) to study
      population shifts during ozonation (1 g ozone/g DOC) at a municipal wastewater
      treatment plant. Escherichia coli, enterococci, and Pseudomonas aeruginosa were
      quantified by polymerase chain reaction (qPCR) and the whole wastewater
      population was analyzed by metagenomic sequencing. The PMA-qPCR experiments
      showed that the abundances of P. aeruginosa didn't change by ozone treatment,
      whereas a reduction was observed for E. coli and enterococci. Results comparing
      conventional cultivation experiments with PMA-qPCR underlined the presence of
      viable but not culturable cells (VBNC) and their regrowth potential after ozone
      treatment. Illumina HiSeq sequencing results with and without PMA treatment
      demonstrated high population similarities in water samples originating from ozone
      inflow sampling sides. Upon using PMA treatment after ozonation, population
      shifts became visible and also underlined the importance of PMA treatment for the
      evaluation of elimination and selection processes during ozonation at WWTPs.
      Amongst a number of 14 most abundant genera identified in the inflow samples, 9
      genera were found to be reduced, whereas 4 genera increased in relative abundance
      and 1 genus almost remained constant. The strongest increase in relative
      abundance after ozonation was detected for Oscillatoria spp., Microcoleus spp.
      and Nitrospira spp. Beside this, a continuous release of Pseudomonas spp.
      (including P. aeruginosa) to the downstream receiving body was confirmed.
      Regrowth experiments demonstrated a high prevalence of P. aeruginosa as part of
      the surviving bacterial population. Summing up, molecular biology analyses in
      combination with live-dead discrimination are comprehensive methods to evaluate
      the elimination processes targeting specific species and/or whole microbial
      populations.

PMID- 29032907
TI  - Pharmaceuticals in water, fish and osprey nestlings in Delaware River and Bay.
AB  - Exposure of wildlife to Active Pharmaceutical Ingredients (APIs) is likely to
      occur but studies of risk are limited. One exposure pathway that has received
      attention is trophic transfer of APIs in a water-fish-osprey food chain. Samples
      of water, fish plasma and osprey plasma were collected from Delaware River and
      Bay, and analyzed for 21 APIs. Only 2 of 21 analytes exceeded method detection
      limits in osprey plasma (acetaminophen and diclofenac) with plasma levels
      typically 2-3 orders of magnitude below human therapeutic concentrations (HTC).
      We built upon a screening level model used to predict osprey exposure to APIs in
      Chesapeake Bay and evaluated whether exposure levels could have been predicted in
      Delaware Bay had we just measured concentrations in water or fish. Use of surface
      water and BCFs did not predict API concentrations in fish well, likely due to
      fish movement patterns, and partitioning and bioaccumulation uncertainties
      associated with these ionizable chemicals. Input of highest measured API
      concentration in fish plasma combined with pharmacokinetic data accurately
      predicted that diclofenac and acetaminophen would be the APIs most likely
      detected in osprey plasma. For the majority of APIs modeled, levels were not
      predicted to exceed 1 ng/mL or method detection limits in osprey plasma. Based on
      the target analytes examined, there is little evidence that APIs represent a
      significant risk to ospreys nesting in Delaware Bay. If an API is present in fish
      orders of magnitude below HTC, sampling of fish-eating birds is unlikely to be
      necessary. However, several human pharmaceuticals accumulated in fish plasma
      within a recommended safety factor for HTC. It is now important to expand the
      scope of diet-based API exposure modeling to include alternative exposure
      pathways (e.g., uptake from landfills, dumps and wastewater treatment plants) and
      geographic locations (developing countries) where API contamination of the
      environment may represent greater risk.

PMID- 29032908
TI  - Mechanistic and kinetic study on the catalytic hydrolysis of COS in small
      clusters of sulfuric acid.
AB  - The catalytic hydrolysis of carbonyl sulfide (COS) and the effect of small
      clusters of H2O and H2SO4 have been studied by theoretical calculations. The
      addition of H2SO4 could increase the enthalpy change (DeltaH<0) and decrease
      relative energy of products (relative energy<0), resulting in hydrolysis reaction
      changed from an endothermic reaction to an exothermic reaction. Further, H2SO4
      decreases the energy barrier by 5.25 kcal/mol, and it enhances the catalytic
      hydrolysis through the hydrogen transfer effect. The (COS + H2SO4-H2O) reaction
      has the lowest energy barrier of 29.97 kcal/mol. Although an excess addition of
      H2O and H2SO4 increases the energy barrier, decreases the catalytic hydrolysis,
      which is consistent with experimental observations. The order of the energy
      barriers for the three reactions from low to high are as follows: COS + H2SO4-H2O
      < COS + H2O + H2SO4-H2O < COS + H2O+(H2SO4)2. Kinetic simulations show that the
      addition of H2SO4 can increase the reaction rate constants. Consequently, adding
      an appropriate amount of sulfuric acid promotes the catalytic hydrolysis of COS
      both kinetically and thermodynamically.

PMID- 29032909
TI  - Subclinical Synovitis Measured by Ultrasound in Rheumatoid Arthritis Patients
      With Clinical Remission Induced by Synthetic and Biological Modifying Disease
      Drugs.
AB  - BACKGROUND: Rheumatoid arthritis (RA) patients with disease in clinical remission
      might show subclinical synovitis, which can be related to the progress of
      structural joint damage. OBJECTIVE: To determine and compare the degree of
      synovial inflammation by ultrasound (US) in patients with RA in clinical
      remission, treated with DMARD or combination therapy with DMARD and anti-TNF.
      METHODS: Hospital-based cross-sectional study of 58 patients with RA in sustained
      remission for at least 6 months by DAS28 <2.6, who attended the Rheumatology
      Service at the Hospital Universitario de Caracas. Patients underwent clinical,
      functional, and laboratory assessments. Ultrasound was performed in hands
      measuring synovial effusion, synovial hypertrophy and power Doppler signal; using
      a semiquantitative 4-point scale of 0=none to 3=severe. Chi-square and t-test
      were used to compare the clinical, functional, laboratory and US assessments
      between the DMARD (N=37) and combination therapy with DMARD and anti-TNF (N=21)
      groups. A p-value <0.05 was considered statistically significant. RESULTS: Out of
      58 patients, 25.9% had remission by US and 74.1% had synovial effusion or
      hypertrophy or positive power Doppler signal. Non-significant differences in US
      synovitis between the two groups were found. CONCLUSIONS: Persistent US activity
      was evident in a high percentage of rheumatoid arthritis patients in clinical
      remission by DAS28. No differences in subclinical synovitis measured by US were
      found between patients with DMARD and anti-TNF-induced clinical remission.

PMID- 29032910
TI  - Venous thromboembolism after laparoscopic or robotic biliopancreatic diversion
      with duodenal switch. Ninety-days outcome of a 10 years' experience.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a feared complication after bariatric
      surgery. Biliopancreatic diversion with duodenal switch (BPD-DS) is a complex
      bariatric procedure that is offered typically to super morbidly obese patients.
      Scarce data exist in reporting VTE outcome and identifying the risk factors
      associated with it after BPD-DS. OBJECTIVE: To determine the risk factors for VTE
      after BPD-DS at 90-day follow-up. SETTING: A nonprofit regional referral center
      and teaching hospital in Pennsylvania. METHODS: A retrospective chart review was
      performed on prospectively collected data over 10 years, between January 1, 2006
      and December 31, 2016. Patients who underwent laparoscopic or robotic BPD-DS were
      included. Preoperative variables, selected risk factors, and methods of VTE
      prophylaxis were analyzed. RESULTS: A total of 662 patients who underwent BPD-DS
      were identified. The mean age was 44.7 +/- 10.4 (20-72) years; 474 patients were
      female (71.7%), and the mean body mass index of the cohort was 50.5 +/- 7.5 (34
      98) kg/m2. Overall, 16 patients (2.4%) experienced VTE complication at 90-days
      follow-up post-BPD-DS with 100% follow-up rate; deep vein thrombosis was
      experienced by 10 patients (1.5%), and 6 patients (0.9%) experienced pulmonary
      embolism (1 patient experience both). None of those patients had a previous
      history of VTE. Only operative time (P value = .009) and length of stay (P value
      <= .001) were associated with VTE events. Other factors such as age, sex, body
      mass index, previous history of VTE, preoperative heparin injection, preoperative
      inferior vena cava filter insertion, intermittent compressive device use,
      interval heparin time, and postoperative chemical prophylaxis did not show a
      statistical association. A logistic regression analysis showed a statistically
      significant increase of VTE outcome with length of stay; odds ratio of 1.161,
      (95% confidence interval, 1.048-1.285), P value = .004. CONCLUSION: With proper
      preoperative evaluation and aggressive VTE prophylaxis protocol, the risk of VTE
      post-BPD-DS is comparable to other bariatric procedures. Every effort should be
      adopted to shorten the length of stay, and thus reduce VTE risk.

PMID- 29032911
TI  - Innervated full thickness grafts in distal finger amputations.
AB  - Innervated full thickness graft will be presented as an option to reconstruct a
      fingertip defect which might result in better sensibility than standard
      reconstruction using a full thickness graft without innervation. Also,
      anastomosing the nerve stumps can decrease the chance of developing neuroma.

PMID- 29032912
TI  - Experiences of civilian nurses in triage during the Iran-Iraq War: An oral
      history.
AB  - PURPOSE: Nurses played a critical role in performing triage during the Iran-Iraq
      War. However, their experiences in triage have not been discussed. Therefore, the
      current study aimed to investigate the triage experiences of civilian nurses
      during the Iran-Iraq War. METHODS: Oral history method and in-depth interviews
      were used to collect data to gain the nurses' experiences in triage. RESULTS:
      Four themes were extracted from the data, which were the development of triage,
      challenging environment to perform triage, development of mobile triage teams,
      and challenges of triage chemical victims for nurses. CONCLUSION: Triage is an
      important skill for nurses to manage critical situations such as disasters and
      wars. Nurses have to be competent in performing triage. Involvement in critical
      situations helps the nurses learn and gain more experience on how to manage
      unexpected events.

PMID- 29032914
TI  - Response to 'Re. Lesson Learned with the Use of Iliac Branch Devices: Single
      Centre 10 Year Experience in 157 Consecutive Procedures'.

PMID- 29032913
TI  - Extracorporeal Shockwave Therapy Plus Rehabilitation for Patients With Chronic
      Plantar Fasciitis Might Reduce Pain and Improve Function but Still Not Lead to
      Increased Activity: A Case-Series Study With Multiple Outcome Measures.
AB  - Plantar fasciitis is a common cause of plantar-aspect heel pain. Although many
      patients will improve, a proportion will have ongoing and sometimes debilitating
      symptoms. Evidence from randomized controlled trials has shown that
      extracorporeal shockwave therapy (ESWT) results in benefits in treating pain.
      However, uncertainties remain whether these benefits translate to improvements in
      overall function. The present prospective case series examined the results from
      35 patients with chronic plantar fasciitis who had undergone a course of ESWT in
      addition to a graded rehabilitation program. Of the 35 subjects, 34% were male,
      and the median age was 50.9 years. The duration of symptoms before ESWT was 24
      months. The results of the present case series demonstrated statistically
      significant improvements in measures of self-reported "average pain" from a
      median of 7.0 of 10 at baseline to 5.0 of 10 at 3 months (p < .001) and of "worst
      pain" from 9.0 of 10 at baseline to 7.0 of 10 at 3 months (p < .001). In
      addition, significant improvements were found in several validated patient-rated
      outcome measures of local foot/ankle function but not in overall markers of
      health, anxiety/depression scores, or activity levels, despite the improvements
      in pain. No statistically significant correlations were found between gender,
      age, or chronicity of symptoms and the improvements seen. No significant side
      effects occurred in the present study. The results of our series support the use
      of ESWT for patients with chronic plantar fasciitis for local pain symptoms;
      however, uncertainties remain regarding global benefits to health.

PMID- 29032915
TI  - Corrigendum to "Risk of Early Recurrent Stroke in Symptomatic Carotid Stenosis"
      [Eur J Vasc Endovasc Surg 49/2 (2015) 137-144].

PMID- 29032916
TI  - Combination of magnesium sulphate and ropivacaine epidural analgesia for hip
      arthroplasty in dogs.
AB  - OBJECTIVE: The aim of this study was to determine whether lumbosacral epidural
      administration of magnesium sulphate added to ropivacaine prolongs and improves
      perioperative analgesia, without adverse effects on motor block duration or hind
      limb neurological function, in dogs undergoing hip arthroplasty. STUDY DESIGN:
      Investigator-blind, controlled, randomized, prospective clinical trial. ANIMALS:
      A group of 20 client-owned dogs undergoing hip arthroplasty were allocated
      randomly to either group C (control, 1 mg kg-1epidural ropivacaine) or group M
      (magnesium, epidural injection of 1 mg kg-1 ropivacaine and 2 mg kg-1magnesium
      sulphate). METHODS: All dogs were premedicated with intramuscular acepromazine.
      General anaesthesia was induced with propofol and maintained with isoflurane in
      oxygen. Intraoperatively, nociception was assessed based on changes in heart
      rate, respiratory rate and mean arterial pressure above baseline values.
      Postoperatively, pain was evaluated with a Sammarco pain score, a Glasgow pain
      scale and a visual analogue scale (VAS). Tarlov's scale was used to quantify
      motor block. All dogs were evaluated at recovery and then 1, 2, 3, 4, 5 and 24
      hours after that. Rescue analgesia was provided during surgery with fentanyl and,
      postoperatively, with buprenorphine. Groups were compared using one-way repeated
      measure analysis of variance followed by the Holm-Sidak method for multiple
      comparison or nonparametric tests when appropriate. RESULTS: The two treatment
      groups did not differ (p > 0.05) with respect to intraoperative physiological
      variables, rescue analgesia, postoperative pain scores (Sammarco q = 1.00;
      Glasgow q = 3.10; VAS q = 0.50) and duration of the motor block (Tarlov's q =
      2.40). CONCLUSIONS AND CLINICAL RELEVANCE: The addition of epidural magnesium to
      ropivacaine did not improve or prolong the analgesia provided by ropivacaine
      alone. Further studies are needed to determine whether an epidural magnesium dose
      of >2 mg kg-1 would exert better analgesia, without causing adverse effects, in
      dogs undergoing orthopaedic surgery.

PMID- 29032917
TI  - Differential Diagnosis of Pulmonary Artery Sarcoma and Central Chronic Pulmonary
      Thromboembolism Using CT and MR Images.
AB  - BACKGROUND: Clinical and imaging manifestations are similar in pulmonary artery
      sarcomas (PAS) and thromboembolic diseases, especially central chronic pulmonary
      thromboembolism (CPTE). The feasibility of utilising clinical imaging tools such
      as computed tomography (CT) and magnetic resonance imaging (MRI) for differential
      diagnosis of PAS and CPTE has not been fully explored, especially MRI. METHODS:
      Patients with PAS (n=18) and central CPTE (n=20) treated at our hospital between
      January 2013 and September 2016 were identified retrospectively. Computed
      tomography and MRI findings of pulmonary artery (PA) filling defects including
      the location, the involvement of pulmonary artery, morphology, signal intensities
      and enhancement in MRI, calcification, sizes of right atrium and ventricle, inner
      diameters of the pulmonary artery trunk and branches, and mediastinal collateral
      circulation in both groups were examined, and differences were analysed by Fisher
      exact test and independent sample t-test. RESULTS: Compared to those of central
      CPTE, PAS lesions were in full shape or expansive growth (p<0.001), and the
      proximal end of the tumours was often bulging or lobulated (p<0.001). These
      lesions were aneurysm- or grape-like distally (p<0.01) with inhomogeneous
      enhancement (p<0.001). The MRI contrast enhancement pattern of PAS lesions were
      cloudy with inhomogeneous delayed enhancement and the time-density curves for
      some of the lesions increased gradually. CONCLUSION: Computed tomographic and MR
      imaging manifestations may resemble PAS and central CPTE; however, some
      manifestations still have great value for the differential diagnosis of these two
      conditions, specifically the morphology and MRI enhancement patterns.

PMID- 29032918
TI  - Adults with 22q11.2 deletion syndrome have a different velopharyngeal anatomy
      with predisposition to velopharyngeal insufficiency.
AB  - AIM: To find out if subjects with 22q11.2 deletion syndrome (DS) have a different
      velopharyngeal anatomy which could cause velopharyngeal insufficiency (VPI).
      METHODS: A prospective study of 16 subjects >16 years of age with 22q11.2 DS,
      without overt cleft palate and without previous VPI surgery, and 48 healthy
      controls >18 years of age were included in the study. Speech was recorded and
      scored blindly by two independent senior speech therapists. All 64 individuals
      had MRI scans, which were analyzed blindly by a consultant radiologist. RESULTS:
      Subjects with 22q11.2 DS had a mild degree of weak pressure consonants (mean
      score); borderline to mild degree of hypernasality and audible nasal emission
      (mean score). All controls had normal speech. When comparing subjects (22q11.2
      DS) to controls, we found the subjects to have the following: A shorter distance
      between left and right points of origin of the levator veli palatini muscle (LVP)
      (p < 0.0001); a more obtuse angle of origin of the LVP (bilaterally) (p < 0.009);
      a thinner LVP bilaterally and in the midline (p < 0.0001); a shorter LVP
      bilaterally (p < 0.0001); a shorter velum (p = 0.007); a larger osseous
      pharyngeal depth:velar length ratio (p = 0.01); a more obtuse anterior cranial
      base angle (nasion to sella to basion) (p < 0.0001) and posterior cranial base
      angle (sella to basion to foramen magnum) (p < 0.0001); a wider velopharyngeal
      width (p = 0.002) and a larger pharyngeal airway volume (p = 0.0007). CONCLUSION:
      Compared with healthy controls, adults with 22q11.2 DS showed a different
      velopharyngeal anatomy, which will make these individuals more prone to VPI.

PMID- 29032919
TI  - Write your first article, but ....

PMID- 29032920
TI  - Cell adhesion mechanosensitivity, an active biological process: Comment on
      "Cellular mechanosensing of the biophysical microenvironment: A review of the
      mathematical models of biophysical regulation of cell responses" by Bo Cheng et
      al.

PMID- 29032921
TI  - Treatment of contact lens related dry eye with antibacterial honey.
AB  - AIM: Contact lens induced dry eye affects approximately 50% of contact lens
      wearers. The aim was to assess the effects of Manuka (Leptospermum sp.) honey eye
      drops (Optimel, Melcare, Australia) on dry eye in contact lens wearers. The
      safety of the honey eye drops in contact lens wear and contact lens wearers'
      compliance were also evaluated. DESIGN: Prospective, randomised, cross over
      study, examiner masked, pilot treatment trial. METHODS: Twenty-four participants
      aged 20 to 55 years with contact lens related dry eye were recruited and
      randomised to two treatment groups; 20 completed the study. One group used
      Optimel eye drops twice a day for two weeks followed by conventional lubricant
      (Systane Ultra, Alcon) therapy for two weeks; the other group completed the
      treatments in the reverse order. Before and after each treatment dry eye
      symptomology, ocular surface inflammation, and tear quantity and quality were
      assessed. Participants completed a daily log detailing their usage of treatments
      and any issues. RESULTS: Dry eye symptoms improved significantly after Optimel
      treatment. Patients with more severe symptoms at baseline showed a greater
      improvement in symptoms. No significant differences were observed in the
      objective signs of dry eye; presumably because of the short treatment duration.
      Seventy-five% of contact lens wearers reported good adherence to Optimel
      treatment and 95% reported no issues using this product. CONCLUSIONS: Optimel Eye
      Drops reduce the symptoms of dry eye in contact lens wearers and are safe to use.
      A longer treatment period to assess the effect on clinical signs of dry eye is
      required.

PMID- 29032922
TI  - Serotonin transporter density in binge eating disorder and pathological gambling:
      A PET study with [11C]MADAM.
AB  - Behavioral addictions, such as pathological gambling (PG) and binge eating
      disorder (BED), appear to be associated with specific changes in brain dopamine
      and opioid function, but the role of other neurotransmitter systems is less
      clear. Given the crucial role of serotonin in a number of psychiatric disorders,
      we aimed to compare brain serotonergic function among individuals with BED, PG
      and healthy controls. Seven BED patients, 13 PG patients and 16 healthy controls
      were scanned with high-resolution positron emission tomography (PET) using the
      serotonin transporter (SERT) tracer [11C]MADAM. Both region-of-interest and voxel
      wise whole brain analyses were performed. Patients with BED showed increased SERT
      binding in the parieto-occipital cortical regions compared to both PG and healthy
      controls, with parallel decreases in binding in the nucleus accumbens, inferior
      temporal gyrus and lateral orbitofrontal cortex. No differences between PG
      patients and controls were observed. None of the subjects were on SSRI
      medications at the time of imaging, and there were no differences in the level of
      depression between PG and BED patients. The results highlight differences in
      brain SERT binding between individuals with BED and PG and provide further
      evidence of different neurobiological underpinnings in behavioral addictions that
      are unrelated to the co-existing mood disorder. The results aid in the
      conceptualization of behavioral addictions by characterizing the underlying
      serotonin changes and provide a framework for additional studies to examine
      syndrome-specific pharmaceutical treatments.

PMID- 29032923
TI  - Is it necessary to dissect the posterior lymph nodes along the splenic vessels
      during total gastrectomy with D2 lymphadenectomy for advanced gastric cancer?
AB  - BACKGROUND: D2 lymphadenectomy including No.10 lymph nodes (LNs) is the standard
      procedure for treating advanced gastric cancer (AGC) via total gastrectomy.
      However, there was no research focusing on the posterior LN dissection along the
      splenic vessels (No.10p LNs). This study is performed to assess the effect of
      dissecting No.10p LNs. METHODS: We analyzed 404 consecutive gastric cancer
      patients who underwent laparoscopic total gastrectomy (LTG) with D2
      lymphadenectomy. There were 68 patients with No.10p LN dissection (No.10p group),
      and 336 patients without No.10p LN dissection (nNo.10p group). The surgical
      outcomes are compared. RESULTS: No.10p LN dissection was preferentially performed
      in patients who were younger and had a lower BMI, concentrated and single
      branched type of splenic artery, and pancreatic tail near the lower pole of the
      spleen. The time for No.10 LN dissection and the number of No.10 LNs were greater
      in the No.10p group than in the nNo.10p group. There was no No.10p LNs
      metastasis, and the numbers of positive No.10 LNs were similar between the two
      groups. The morbidity and mortality rates of the No.10p group were comparable to
      those of the nNo.10p group. The overall survival (OS) rates of the two groups
      were not significantly different (P > 0.05). CONCLUSIONS: Although No.10p LN
      dissection might retrieve more No.10 LNs, operation times were longer, and the
      number of positive No.10 LNs and the OS rate were not improved. It might be no
      necessary to dissect No.10p LNs during total gastrectomy with D2 lymphadenectomy
      for AGC.

PMID- 29032925
TI  - Current status of the etiology of candidiasis in Mexico.
AB  - This study presents a systematic review of the literature on the etiology of
      superficial and invasive candidiasis in Mexico reported from 2005 to 2015. The
      data have shown that Candida albicans is the most prevalent species with an
      increasing tendency of the non-C. albicans Candida species, as reported in other
      countries. The use of phenotypical methods in the identification of the yeasts
      limits the identification at the species level, particularly in species that are
      part of complexes, this is important because the identification only at the genus
      level leads to inadequate treatment due to the different susceptibility to the
      antifungals among species. In addition, this finding reveals the need to
      implement in clinical laboratories the molecular methods for the correct
      identification of the species involved, and the antifungal susceptibility tests
      to prevent the etiological changes associated with a poor therapeutic management.

PMID- 29032926
TI  - Message from an Urgent Care PrEP Provider for Health Care Professionals.

PMID- 29032927
TI  - Mortality from systemic erythematosus lupus in Brazil: evaluation of causes
      according to the government health database.
AB  - OBJECTIVE: To characterize the causes of mortality in patients with systemic
      lupus erythematosus (SLE) in Brazil between 2002 and 2011. METHODS: An
      exploratory ecological study of a time series using data from the Mortality
      Information System of DATASUS, the Department of the Unified Health System
      (Brazil's National Health System). RESULTS: Brazil's SLE mortality rate was 4.76
      deaths/105 inhabitants. The mortality rate was higher in the Midwest, North and
      Southeast regions than in the country as a whole. There were 6.3% fewer and 4.2%
      more deaths than expected in the Northeast and Southeast regions, respectively.
      The mean age at death was 40.7+/-18 years, and 45.61% of deaths occurred between
      the ages of 20 and 39. Incidence was highest in women (90.7%) and whites (49.2%).
      Disorders of the musculoskeletal system and connective tissue were mentioned as
      an underlying cause of death in 77.5% of cases, and diseases of the circulatory
      system and infectious and parasitic diseases were also noted in fewer cases. SLE
      was mentioned as an underlying cause of death in 77% of cases, with no difference
      between the Brazilian regions (p=0.2058). The main SLE-related causes of death
      were, sequentially, diseases of the respiratory and circulatory systems and
      infectious and parasitic diseases. CONCLUSIONS: This study identified a need for
      greater control of risk factors for cardiovascular diseases and a better
      understanding of the pathogenesis of atherosclerosis in SLE. Infectious causes
      are still frequent, and management should be improved, especially in the early
      stages of the disease.

PMID- 29032928
TI  - Clinical heterogeneity in Andersen-Tawil syndrome.

PMID- 29032929
TI  - Binding of triazole-linked galactosyl arylsulfonamides to galectin-3 affects
      Trypanosoma cruzi cell invasion.
AB  - The synthesis of the O-3 triazole-linked galactosyl arylsulfonamides 1-7 as
      potential inhibitors of Trypanosoma cruzi cell invasion is described. These
      target compounds were synthesized by Cu(I)-catalysed azide-alkyne cycloaddition
      reaction ('click chemistry') between different azide arylsulfonamides and the
      alkyne-based sugar 3-O-propynyl-betaGalOMe. Inhibition assays of T. cruzi cell
      invasion with compounds 1-7 showed reduced values of infection index (~20) for
      compounds 3 and 5, bearing the corresponding 5-methylisoxazole and 2,4
      dimethoxypyrimidine groups, which also presented higher binding affinities to
      galectin-3 (EC50 17-18 MUM) in Corning Epic label-free assays. In agreement with
      experimental results, the assessment of the theoretical binding of compounds 1-7
      to galectin-3 by MM/PBSA method displayed higher affinities for compounds 3 (-9.7
      kcal/mol) and 5 (-11.1 kcal/mol). Overall, these achievements highlight compounds
      3 and 5 as potential T. cruzi cell invasion blockers by means of a galectin-3
      binding-related mechanism, revealing galectin-3 as an important host target for
      design of novel anti-trypanosomal agents.

PMID- 29032924
TI  - Epidemiology of rare cancers and inequalities in oncologic outcomes.
AB  - Rare cancers epidemiology is better known compared to the other rare diseases.
      Thanks to the long history of the European population-based cancer registries and
      to the EUROCARE huge database, the burden of rare cancers has been estimated the
      European (EU28) population. A considerable fraction of all cancers is represented
      by rare cancers (24%). They are a heterogeneous group of diseases, but they share
      similar problems: uncertainty of diagnosis, lack of therapies, poor research
      opportunities, difficulties in clinical trials, lack of expertise and of centres
      of reference. This paper analyses the major epidemiological indicators of
      frequency (incidence and prevalence) and outcome (5-year survival) of all rare
      cancers combined and of selected rare cancers that will be in depth treated in
      this monographic issue. Source of the results is the RARECAREnet search tool, a
      database publicly available. Disparities both in incidence and survival, and
      consequently in prevalence of rare cancers were reported across European
      countries. Major differences were shown in outcome: 5-year relative survival for
      all rare cancers together, adjusted by age and case-mix, varied from 55% or more
      (Italy, Germany, Belgium and Iceland) and less than 40% (Bulgaria, Lithuania and
      Slovakia). Similarly, for all the analyzed rare cancers, a large survival gap was
      observed between the Eastern and the Nordic and Central European regions.
      Dramatic geographical variations were assessed for curable cancers like
      testicular and non epithelial ovarian cancers. Geographical difference in the
      annual age-adjusted incidence rates for all rare cancers together varied between
      >140 per 100,000 (Italy, Scotland, France, Germany, and Switzerland) and <100
      (Finland, Portugal, Malta, and Poland). Prevalence, the major indicator of public
      health resources needs, was about 7-8 times larger than incidence. Most of rare
      cancers require complex surgical treatment, thus a multidisciplinary approach is
      essential and treatment should be provided in centres of expertise and/or in
      networks including expert centres. Networking is the most appropriate answer to
      the issues pertaining to rare cancers. Actually, in Europe, an opportunity to
      improve outcome and reduce disparities is provided by the creation of the
      European Reference Networks for rare diseases (ERNs). The Joint Action of rare
      cancers (JARC) is a major European initiative aimed to support the mission of the
      ERNs. The role of population based cancer registries still remains crucial to
      describe rare cancers management and outcome in the real word and to evaluate
      progresses made at the country and at the European level.

PMID- 29032930
TI  - 3'-Hydroxy-3,4'-dimethoxyflavone blocks tubulin polymerization and is a potent
      apoptotic inducer in human SK-MEL-1 melanoma cells.
AB  - Flavonoids are naturally occurring polyphenolic compounds and are among the most
      promising anticancer agents. A series of flavonols and their 3-methyl ether
      derivatives were synthesized and assessed for cytotoxicity. It was found that 3'
      hydroxy-3,4'-dimethoxyflavone (flavonoid 7a) displayed strong cytotoxicity
      against human SK-MEL-1 melanoma cells and blocked tubulin polymerization, but had
      no significant cytotoxic effects against quiescent or proliferating human
      peripheral blood mononuclear cells. Our analyses showed that flavonoid 7a induces
      G2-M cell cycle arrest and apoptosis in melanoma cells which is associated with
      cytochrome c release and activation of both extrinsic and intrinsic apoptotic
      pathways of cell death.

PMID- 29032931
TI  - Synthesis of novel 1,2,5-oxadiazoles and evaluation of action against
      Acinetobacter baumannii.
AB  - With multidrug resistant bacteria on the rise, novel antibiotics are becoming
      highly sought after. In 2008, eleven compounds were identified by high throughput
      screening as inhibitors of BasE, a key enzyme of the non-ribosomal peptide
      synthetase pathway found in Acinetobacter baumannii. Herein, we describe the
      preparation of four structurally similar heterocyclic lead compounds from that
      study, including one 1,2,5-oxadiazole. A further library of 30 analogues
      containing the oxadiazole moiety was then generated. All compounds were screened
      against Acinetobacter baumannii and their minimum inhibitory concentration data
      is reported, with (E)-3-(2-hydroxyphenyl)-N-(4-methyl-1,2,5-oxadiazol-3
      yl)acrylamide 32 found to have an MIC of 0.5mM. This work provides the foundation
      for further investigation of 1,2,5-oxadizoles as novel inhibitors of A.
      baumannii.

PMID- 29032932
TI  - MY APPROACH to the elderly patient with resistant hypertension.

PMID- 29032933
TI  - MY APPROACH to the Athlete With Wolff-Parkinson-White Syndrome (WPW).

PMID- 29032934
TI  - MY APPROACH to the patient with left main disease.

PMID- 29032935
TI  - MY APPROACH to the patient with heart failure and improved ejection fraction*.

PMID- 29032936
TI  - Editorial commentary: Percutaneous edge-to-edge mitral valve repair with
      Mitraclip: State of the art and new perspectives.

PMID- 29032937
TI  - Challenges and Opportunities to Scale Up Cardiovascular Disease Secondary
      Prevention in Latin America and the Caribbean.

PMID- 29032938
TI  - The JAK/STAT signaling pathway and photobiomodulation in chronic wound healing.
AB  - Wound healing is a physiological process that occurs in overlapping phases namely
      hemostasis, inflammation, proliferation, and remodeling. Chronic wounds fail to
      proceed through these reparative processes to achieve the functional integrity
      within the expected time. Wound healing relies upon growth factors and cytokines
      for the precise and accurate regulation of cellular responses. These are achieved
      through the use of complex growth factor/cytokine induced signaling pathways. The
      Janus kinase/signal transducers and activators of transcription (JAK/STAT)
      pathway transmits extracellular signals to the nucleus for the transcription of
      genes involved in proliferation and differentiation, to name but a few.
      Photobiomodulation (PBM) is an emerging area of interest within the scientific
      community and researchers are currently exploring its underlying mechanism and
      the associated signaling pathways involved. PBM is a light based therapy making
      use of low powered lasers or light emitting diodes (LEDs) to enhance tissue
      repair, and reduce pain and inflammation. Current conventional treatments for
      chronic wounds are frequently associated with failure and have limited
      therapeutic efficacy. Thus there is a need for efficient wound healing
      interventions and the identification and development of new treatments is
      required. In this review we summarize the involvement of JAK/STAT signaling and
      PBM in chronic wounds.

PMID- 29032939
TI  - Reply.

PMID- 29032940
TI  - Molecular basis of alpha-thalassemia.
AB  - alpha-Thalassemia is an inherited, autosomal recessive, disorder characterized by
      a microcytic hypochromic anemia. It is one of the most common monogenic gene
      disorders in the world population. The clinical severity varies from almost
      asymptomatic, to mild microcytic hypochromic, and to a lethal hemolytic
      condition, called Hb Bart's Hydrops Foetalis Syndrome. The molecular basis are
      usually deletions and less frequently, point mutations affecting the expression
      of one or more of the duplicated alpha-genes. The clinical variation and increase
      in disease severity is directly related to the decreased expression of one, two,
      three or four copies of the alpha-globin genes. Deletions and point mutations in
      the alpha-globin genes and their regulatory elements have been studied
      extensively in carriers and patients and these studies have given insight into
      the alpha-globin genes are regulated. By looking at naturally occurring deletions
      and point mutations, our knowledge of globin-gene regulation and expression will
      continue to increase and will lead to new targets of therapy.

PMID- 29032941
TI  - Ferritin iron regulators, PCBP1 and NCOA4, respond to cellular iron status in
      developing red cells.
AB  - Developing red blood cells exhibit multiple, redundant systems for regulating and
      coordinating the uptake of iron, the synthesis of heme, and the formation of
      hemoglobin during terminal differentiation. We recently described the roles of
      poly rC-binding protein (PCBP1) and nuclear coactivator 4 (NCOA4) in mediating
      the flux of iron through ferritin in developing erythroid cells, with PCBP1, an
      iron chaperone, delivering iron to ferritin and NCOA4, an autophagic cargo
      receptor, directing ferritin to the lysosome for degradation and iron release.
      Ferritin iron flux is critical, as mice lacking these factors develop microcytic
      anemia. Here we report that these processes are regulated by cellular iron levels
      in a murine model of ex vivo terminal differentiation. PCBP1 delivers iron to
      ferritin via a direct protein-protein interaction. This interaction is
      developmentally regulated, enhanced by iron deprivation, and inhibited by iron
      excess, both in developing cells and in vitro. NCOA4 activity also exhibited
      developmental regulation and regulation by cellular iron levels. Excess iron
      uptake during differentiation triggered lysosomal degradation of NCOA4, which was
      dependent on the E3 ubiquitin ligase HERC2. Thus, developing red blood cells
      express a series of proteins that both mediate and regulate the flux of iron to
      the mitochondria.

PMID- 29032942
TI  - Aspartate aminotransferase-to-platelet ratio predicts response to transarterial
      chemoembolisation and prognosis in hepatocellular carcinoma patients.
AB  - AIM: To evaluate the value of the aspartate aminotransferase-to-platelet ratio
      index (APRI) for hepatocellular carcinoma (HCC) patients who underwent
      transarterial chemoembolisation (TACE). MATERIALS AND METHODS: A total of 315
      patients were enrolled, who were randomly divided into the training cohort
      (n=158) and the validation cohort (n=157). The optimal cut-off value of the APRI
      was determined using the X-tile software in the training cohort, and was
      validated in the validation cohort. Several serum-based markers, neutrophil-to
      lymphocyte (N/L) and aspartate aminotransferase-to-alanine aminotransferase
      (AST/ALT) ratios were included to compare with the APRI. To predict individual
      survival rate, independent predictors were included to build a nomogram. RESULTS:
      Using the X-tile, a cut-off value of the APRI as 0.40 was yielded to distinguish
      patients with distinct outcomes in the training cohort, but failed for the N/L
      and ALT/AST ratios. In the training cohort, 66 patients with high APRI had poorer
      survival (p<0.001) than did 92 patients with low APRI. Using the same cut-off
      value of APRI, 61 patients with high APRI had poorer survival (p<0.001) than did
      96 patients with low APRI in the validation cohort. Furthermore, a nomogram,
      including the APRI, TACE cycles, tumour size, and tumour number, was built based
      on the training cohort, and validated well in the validation cohort (concordance
      index [C-index] 0.713). CONCLUSION: The APRI is a promising marker to predict
      treatment response and outcome for HCC patients after TACE treatment.

PMID- 29032943
TI  - Assessing the validity of oscillometric device for blood pressure measurement in
      a large population-based epidemiologic study.
AB  - To evaluate the accuracy of the Omron HBP-1300, an automatic device for blood
      pressure (BP) measurement, compared with the standard auscultatory method with a
      mercury sphygmomanometer, we conducted a large population-based survey. From 2012
      to 2015, a total of 500,000 participants were randomly selected from the 262
      urban cities and rural counties in China, of them BP was measured three times
      simultaneously with mercury sphygmomanometer and Omron HBP-1300 in 37,816
      participants. Bias was estimated as the average of the auscultatory measurements
      minus the average of the oscillometric measurements, with its corresponding 95%
      limits of agreement. The Association for the Advancement of Medical
      Instrumentation standards and British Hypertension Society protocols were used to
      evaluate the accuracy of the oscillometric device. The results showed that the
      Omron underestimated systolic BP by 1.0 mm Hg (95% limits of agreement: -9.2,
      11.2) and underestimated diastolic BP by 0.2 mm Hg (95% limits of agreement: 
      8.5, 8.1). The bias in systolic BP values was related to heart rate, systolic BP,
      and pulse pressure level, while the bias in diastolic BP was related to the heart
      rate and pulse pressure level. Omron HBP-1300 passed the Association for the
      Advancement of Medical Instrumentation standards and British Hypertension Society
      protocol requirements. The sensitivity and specificity of the Omron HBP-1300 to
      detect hypertension were 86.2% and 98.0%, respectively. Our results showed that
      the Omron HBP-1300 could be used for measuring BP in large epidemiology studies.
      The bias of BP measurement was related to the age, systolic BP, and pulse
      pressure level.

PMID- 29032944
TI  - [Observational study of outpatient unit duration of stay depending on the route
      of administration (intravenous vs subcutaneous) for a targeted therapy].
AB  - New routes of administration available for some targeted therapies, especially
      subcutaneous injections, have an impact not only on the patients' daycare
      experience, but also on the unit's organization. This observational study
      conducted on 48 voluntary patients at the Institut universitaire du cancer
      Toulouse-Oncopole shows that the mean duration of the outpatient unit stay is
      diminished by one hour when a subcutaneous injection is used instead of an
      intravenous route. This duration decrease is mainly caused by an 82% average
      reduction in treatment duration. However, the waiting times before and after the
      treatment itself are not significantly impacted. Organizational methods related
      to the treatment prescription and preparation remain indeed the same. Anticipated
      prescription is not noticeably impacted either. This reduction of the duration of
      stay will truly be obtained if the whole unit's organization is adapted.

PMID- 29032945
TI  - Contraception options: Aspects unique to adolescent and young adult.
AB  - Sexual health for adolescents is based on three components: recognizing sexual
      rights, sexuality education and counseling, and thirdly confidential high quality
      services. Contraception needs to include prevention of both STIs and pregnancies.
      The first option for adolescents is condoms backed-up by emergency contraception;
      and later hormonal contraceptives in a longer, mutually monogamous relationship.
      Condoms and hormonal contraception together can be well recommended for
      adolescents for dual protection. Long acting reversible contraception (LARC)
      including both intrauterine contraception and implants are safe and highly
      effective and thus well suited for adolescents. Improved contraceptive methods do
      not automatically lead to reduced numbers of adolescent abortions. When sexuality
      education, proper counseling and sexual health services are all provided, it is
      possible to profoundly improve adolescent sexual health.

PMID- 29032946
TI  - Uterine Artery Embolization for the Treatment of Adenomyosis: A Systematic Review
      and Meta-Analysis.
AB  - The effect of uterine artery embolization (UAE) on symptomatic adenomyosis was
      evaluated in a systematic review and meta-analysis. Four groups were evaluated:
      short-term (< 12 months) pure adenomyosis, short-term adenomyosis with fibroids
      (combined adenomyosis), long-term (> 12 months) pure adenomyosis, and long-term
      combined adenomyosis. Improvement of symptoms occurred in 83.1% (872/1,049) of
      patients. Reported symptom reduction was 4.8% greater in the short-term combined
      group (P = .169) and 11.4% greater in the long-term combined group (P = .003).
      Uterine volume was reduced in all patients at 3 months. The effects of UAE on
      symptom improvement and uterine volume reduction in patients with adenomyosis are
      encouraging.

PMID- 29032947
TI  - Temporal distribution of alcohol related facial fractures.
AB  - OBJECTIVES: This study aimed to address 2 important aspects of temporal pattern
      in alcohol-related facial fractures: (1) comparison of temporal pattern of
      alcohol-related facial fracture (alcohol group) presentation with non-alcohol
      related fracture (non-alcohol group) presentation; (2) temporal pattern of
      patient demographic characteristics, injury characteristics, and surgical
      management in the alcohol group presentation. STUDY DESIGN: This study
      retrospectively examined the Victorian admitted episodes data set (VAED) for the
      years 2010 to 2013. VAED is a standardized set of data collected during all
      hospital presentations in Victoria. RESULTS: The study found higher incidence of
      alcohol-related facial fracture presentations during weekends and during the
      summer and spring months compared with non-alcohol-related fractures
      (statistically significant). Alcohol-related facial fractures are more likely to
      involve male patients in the 20- to 29-year age group, occur as a result of
      interpersonal violence, and require shorter hospital stays during weekend
      admissions (statistically significant). No statistically significant relationship
      has been observed in seasonal variation across all variables. CONCLUSIONS: This
      study found distinct characteristics in temporal distribution of alcohol-related
      facial fractures. These characteristics are, in particular, significant in
      weekend trauma admissions. Such information is important in workforce planning,
      resource distribution, and implementation of injury prevention programs.

PMID- 29032948
TI  - Anxiety and pain related to mandibular block injections: comparison of self
      reported measures and physiological response.
AB  - OBJECTIVE: The aim of this study was to determine whether patients with a pain
      score >=7 (high pain group) after a mandibular block injection had a higher
      physiologic response compared with patients with scores <7 (low pain group).
      STUDY DESIGN: Before oral surgery, patients (n = 66) filled out questionnaires to
      measure anxiety and expected pain. The questionnaires also assessed patients'
      experiences with dental injections and dental anxiety, as well as their emotional
      state and intensity of anxiety. Before, during, and after the injection,
      physiologic responses were measured by using Nexus-10. Patients were then asked
      about the pain and anxiety they had experienced. RESULTS: The mean score for pain
      experienced was 3.45 (standard deviation 2.17) on an 11-point rating scale. Eight
      patients (12.1%) experienced high injection pain. There was a significant
      increase in mean sweat secretion and a significant decrease in mean respiration
      between the relaxing phase and the injection phase. There was a significant
      positive relationship between experienced anxiety and mean heart rate during the
      injection phase. No significant difference in physiologic response was found
      between patients who experienced high pain and those who experienced low pain.
      CONCLUSIONS: Reported pain was not associated with the physiologic response of
      patients receiving mandibular block injections.

PMID- 29032949
TI  - Correction of hyperleucinemia in MSUD patients on leucine-free dietary therapy.
AB  - PURPOSE: Maple Syrup Urine Disease (MSUD) is a rare disorder of branched-chain
      amino acid catabolism associated with encephalopathy from accumulation of
      leucine. Leucine is closely monitored during normal growth and particularly
      during acute illness. As most hospitals do not have access to rapid plasma amino
      acid quantification, the initial management is often empirical. A model
      describing the reduction of plasma leucine in hyperleucinemic patients on leucine
      free formula would help to guide management and optimize testing frequency.
      METHODS: We retrospectively reviewed charts from 15 MSUD patients comprising 29
      episodes of hyperleucinemia that were managed with leucine-free formula. Episodes
      were categorized by clinical presentation. RESULTS: Upon leucine restriction,
      plasma leucine concentrations fell exponentially at a rate proportional to
      approximately 50% of the starting value over each 24-hour period. Recovery
      appears to be sensitive to clinical status and triggering event of the
      hyperleucinemic episode. Patients with upper respiratory infections generally
      recovered slowly, while cases of dietary non-adherence resolved more quickly.
      CONCLUSION: This general model may help anticipate leucine levels during clinical
      management of MSUD patients when using nutritional support and leucine-free
      formula. The response of individual patients may vary depending on clinical
      status and triggering factors.

PMID- 29032951
TI  - Special Section: Review articles on decision making and patient education
      interventions.

PMID- 29032950
TI  - Trajectories of fasting plasma glucose variability and mortality in type 2
      diabetes.
AB  - AIM: To investigate the effect of changes in fasting plasma glucose (FPG)
      variability, as assessed by 2-year trajectories of FPG variability, on mortality
      risk in patients with type 2 diabetes (T2D). METHODS: From 2009 to 2012,
      outpatients with T2D, aged>18 years, were enrolled from a medical centre. FPG was
      measured every 3 months for 2 years in 3569 people. For each of the eight 3-month
      intervals, FPG variability and means were calculated, with variability defined as
      the coefficient of variation of FPG. Also, trajectories of FPG variability and
      means were determined separately, using group-based trajectory analysis with
      latent class growth models. These models were fitted using the SAS Proc Traj
      procedure. The primary outcome was all-cause mortality, which was followed-up to
      the end of 2014. RESULTS: Five distinct trajectories of FPG variability (low,
      increasing, fluctuating, decreasing and high) and means (well controlled, stable
      control, worsening control, improving control and poor control) were established.
      The five trajectories of mean FPG were all associated with the same mortality
      risk. In contrast, in comparison to the low FPG variability trajectory, the
      fluctuating, decreasing and high variability trajectories all had significantly
      higher risks of mortality, with respective hazards ratios of 2.63 (95% CI: 1.40
      4.93; P=0.003), 2.78 (95% CI: 1.33-5.80; P=0.007) and 4.44 (95% CI: 1.78-11.06;
      P=0.001) after multivariable adjustment. CONCLUSION: Changes in FPG variability
      were independently associated with increased mortality risk in patients with T2D.

PMID- 29032952
TI  - Corrigendum to "Protocols for the analytical characterization of therapeutic
      monoclonal antibodies. I-Non-denaturing chromatographic techniques" [J.
      Chromatogr. B 1058 (2017) 73-84].

PMID- 29032953
TI  - Abolishment of proximal tubule albumin endocytosis does not affect plasma albumin
      during nephrotic syndrome in mice.
AB  - The megalin/cubilin receptor complex is required for proximal tubular endocytosis
      and degradation of filtered albumin. An additional high-capacity retrieval
      pathway of intact albumin for the recovery of large amounts of filtered albumin
      has been proposed, possibly involving cooperation between megalin/cubilin and the
      neonatal Fc receptor. To clarify the potential role of such a pathway, we
      examined the effects of megalin/cubilin gene inactivation on tubular albumin
      uptake and plasma albumin levels in nephrotic, podocin knockout mice.
      Immunofluorescence microscopy of megalin/cubilin/podocin knockout mouse kidneys
      demonstrated abolishment of proximal tubule albumin uptake, in contrast to the
      excessive albumin accumulation observed in podocin knockout mice compared to
      controls. Correspondingly, urinary albumin excretion was increased 1.4 fold in
      megalin/cubilin/podocin compared to podocin knockout mice (albumin/creatinine:
      226 vs. 157 mg/mg). However, no difference in plasma albumin levels was observed
      between megalin/cubilin/podocin and podocin knockout mice, as both were reduced
      to approximately 40% of controls. There were no differences in liver albumin
      synthesis by mRNA levels and protein abundance. Thus, megalin/cubilin knockout
      efficiently blocks proximal tubular albumin uptake in nephrotic mice but plasma
      albumin levels did not differ as a result of megalin/cubilin-deficiency,
      suggesting no significance of the megalin/cubilin-pathway for albumin homeostasis
      by retrieval of intact albumin.

PMID- 29032954
TI  - Coronary flow reserve is predictive of the risk of cardiovascular death
      regardless of chronic kidney disease stage.
AB  - Microvascular rarefaction is found in experimental uremia, but data from patients
      with chronic kidney disease (CKD) are limited. We therefore quantified absolute
      myocardial blood flow and coronary flow reserve (the ratio of peak to resting
      flow) from myocardial perfusion positron emission tomography scans at a single
      institution. Individuals were classified into standard CKD categories based on
      the estimated glomerular filtration rate. Associations of coronary flow reserve
      with CKD stage and cardiovascular mortality were analyzed in models adjusted for
      cardiovascular risk factors. The coronary flow reserve was significantly
      associated with CKD stage, declining in early CKD, but it did not differ
      significantly among individuals with stage 4, 5, and dialysis-dependent CKD. Flow
      reserve with preserved kidney function was 2.01, 2.06 in stage 1 CKD, 1.91 in
      stage 2, 1.68 in stage 3, 1.54 in stage 4, 1.66 in stage 5, and 1.55 in dialysis
      dependent CKD. Coronary flow reserve was significantly associated with
      cardiovascular mortality in adjusted models (hazard ratio 0.76, 95% confidence
      interval: 0.63-0.92 per tertile of coronary flow reserve) without evidence of
      effect modification by CKD. Thus, coronary flow reserve is strongly associated
      with cardiovascular risk regardless of CKD severity and is low in early stage CKD
      without further decrement in stage 5 or dialysis-dependent CKD. This suggests
      that CKD physiology rather than the effects of dialysis is the primary driver of
      microvascular disease. Our findings highlight the potential contribution of
      microvascular dysfunction to cardiovascular risk in CKD and the need to define
      mechanisms linking low coronary flow reserve to mortality.

PMID- 29032955
TI  - Re: Letter to the Editor of Public Health in response to 'Evaluation of
      compliance with the Spanish Code of self-regulation of food and drinks
      advertising directed at children under the age of 12 years in Spain, 2012'.

PMID- 29032956
TI  - Evaluation of surface treatments of monolithic zirconia in different sintering
      stages.
AB  - PURPOSE: This study evaluated the effect of surface treatment of zirconia in pre
      sintered and post-sintered stages on its surface roughness, phase transformation,
      and biaxial flexural strength (BFS). METHODS: Zirconia ceramic discs (n=40)
      having a final dimensions of 12mm diameter and 1.2mm thickness were milled then
      divided into three main groups according to the type of surface treatment
      performed (Group 1 (n=16); air-abrasion using Al2O3 particles, Group 2 (n=16);
      silica coating using Rocatec soft, and Group 3 (n=8); a control group receiving
      no surface treatment). Groups 1 and 2 were divided into two subgroups each
      according to the stage in which the surface treatment was performed (Subgroup A;
      surface treatment performed in the pre-sintered stage and subgroup B; surface
      treatment performed in the post-sintered stage). Surface roughness, phase
      transformation, and biaxial flexural strength (BFS) were later assessed. Data was
      then analyzed using two-way ANOVA and Tukey post-hoc tests at a significance
      level of p<=0.05. RESULTS: Subgroups treated in the pre-sintered stage showed
      higher mean Ra in MUm (1.81+/-0.36) when compared to the subgroups treated in the
      post-sintered (0.68+/-0.07) stage and the control group (0.51+/-0.10) (p<=0.05).
      The pre-sintered treated group and the control showed no monoclinic phase while
      the post-sintered group showed significantly higher portions of monoclinic phase.
      Regarding BFS the post-sintered treated group had statistically significant
      higher values in MPa (1228+/-81) when compared to the pre-sintered treated group
      (940+/-101) and the control (1019+/-82) (p<=0.05). CONCLUSIONS: Air abrasion in
      the pre-sintered stage might be a promising surface treatment method to produce
      promising surface roughness values of zirconia without subjecting it to early
      degradation.

PMID- 29032958
TI  - Treatment of iron deficiency is getting trendy.

PMID- 29032957
TI  - Iron absorption from oral iron supplements given on consecutive versus alternate
      days and as single morning doses versus twice-daily split dosing in iron-depleted
      women: two open-label, randomised controlled trials.
AB  - BACKGROUND: Current guidelines to treat iron deficiency recommend daily provision
      of ferrous iron divided through the day to increase absorption. However, daily
      dosing and split dosing might increase serum hepcidin and decrease iron
      absorption from subsequent doses. Our study aim was to compare iron absorption
      from oral iron supplements given on consecutive versus alternate days and given
      as single morning doses versus twice-daily split dosing. METHODS: We did two
      prospective, open-label, randomised controlled trials assessing iron absorption
      using (54Fe)-labelled, (57Fe)-labelled, or (58Fe)-labelled ferrous sulfate in
      iron-depleted (serum ferritin <=25 MUg/L) women aged 18-40 years recruited from
      ETH Zurich and the University of Zurich, Switzerland. In study 1, women were
      randomly assigned (1:1) to two groups. One group was given 60 mg iron at 0800 h
      (+/-1 h) on consecutive days for 14 days, and the other group was given the same
      doses on alternate days for 28 days. In study 2, women were assigned to two
      groups, stratified by serum ferritin so that two groups with similar iron
      statuses could be formed. One group was given 120 mg iron at 0800 h (+/-1 h) and
      the other was given the dose split into two divided doses of 60 mg at 0800 h (+/
      1 h) and 1700 h (+/-1 h) for three consecutive days. 14 days after the final
      dose, the groups were each crossed over to the other regimen. Within-individual
      comparisons were done. The co-primary outcomes in both studies were iron
      bioavailability (total and fractional iron absorption), assessed by measuring the
      isotopic label abundance in erythrocytes 14 days after administration, and serum
      hepcidin. Group allocations in both studies were not masked and primary and
      safety analyses were done on an intention-to-treat basis. The studies were
      registered at ClinicalTrials.gov, numbers NCT02175888 (study 1) and NCT02177851
      (study 2) and are complete. FINDINGS: For study 1, 40 women were enrolled on Oct
      15-29, 2015. 21 women were assigned to the consecutive-day group and 19 to the
      alternate-day group. At the end of treatment (14 days for the consecutive-day
      group and 28 days for the alternate-day group), geometric mean (-SD, +SD)
      cumulative fractional iron absorptions were 16.3% (9.3, 28.8) in the consecutive
      day group versus 21.8% (13.7, 34.6) in the alternate-day group (p=0.0013), and
      cumulative total iron absorption was 131.0 mg (71.4, 240.5) versus 175.3 mg
      (110.3, 278.5; p=0.0010). During the first 14 days of supplementation in both
      groups, serum hepcidin was higher in the consecutive-day group than the alternate
      day group (p=0.0031). In study 2, 20 women were enrolled between Aug 13 and 18,
      2015. Ten women were assigned to receive once-daily dosing and ten were assigned
      to receive twice-daily divided dosing. No significant differences were seen in
      fractional (day 1-3 geometric mean: 11.8% [7.1, 19.4] once daily vs 13.1% [8.2,
      20.7] twice daily; p=0.33) or total iron absorption (day 1-3: 44.3 mg [29.4,
      66.7] once daily vs 49.4 [35.2, 69.4] twice daily; p=0.33) between the two dosing
      regimens. Twice-daily divided doses resulted in a higher serum hepcidin
      concentration than once-daily dosing (p=0.013). No grade 3 or 4 adverse events
      were reported in either study. INTERPRETATION: In iron-depleted women, providing
      iron supplements daily as divided doses increases serum hepcidin and reduces iron
      absorption. Providing iron supplements on alternate days and in single doses
      optimises iron absorption and might be a preferable dosing regimen. These
      findings should be confirmed in iron-deficient anaemic patients. FUNDING: Swiss
      National Science Foundation, Bern, Switzerland.

PMID- 29032959
TI  - Clinical application of cell, gene and tissue therapies in Spain.
AB  - Scientific and technical advances in the areas of biomedicine and regenerative
      medicine have enabled the development of new treatments known as "advanced
      therapies", which encompass cell therapy, genetics and tissue engineering. The
      biologic products that can be manufactured from these elements are classified
      from the standpoint of the Spanish Agency of Medication and Health Products in
      advanced drug therapies, blood products and transplants. This review seeks to
      provide scientific and administrative information for clinicians on the use of
      these biologic resources.

PMID- 29032960
TI  - Correlation between oxyhaemoglobin saturation by pulse oximetry and partial
      pressure of oxygen in patients with acute respiratory failure.
AB  - OBJECTIVES: To ascertain the correlation between the partial pressure of oxygen
      (PaO2) and oxyhaemoglobin saturation by pulse oximetry (SpO2) in patients who
      were admitted to the emergency department with suspected acute respiratory
      failure. MATERIAL AND METHODS: A prospective, observational multicentre study was
      conducted in the emergency departments of 3 Spanish hospitals. RESULTS: The study
      included 166 patients who presented mean+/-standard deviation PaO2, SpO2 and
      fraction of inspired oxygen (FiO2) values of 61.64+/-17.3mmHg, 87.61+/-8.8% and
      0.28+/-0.15%, respectively. The median PaO2/FiO2 and SpO2/FiO2 ratios were 256.6
      and 359.2, respectively. The correlation between PaO2/FiO2 and the SpO2/FiO2 was
      0.745 (P<.001). CONCLUSIONS: The SpO2/FiO2 ratio can be used to calculate
      PaO2/FiO2 and determine the oxygenation state of patients with acute respiratory
      failure.

PMID- 29032961
TI  - Optimal Quantification of Contact Inhibition in Cell Populations.
AB  - Contact inhibition refers to a reduction in the rate of cell migration and/or
      cell proliferation in regions of high cell density. Under normal conditions,
      contact inhibition is associated with the proper functioning tissues, whereas
      abnormal regulation of contact inhibition is associated with pathological
      conditions, such as tumor spreading. Unfortunately, standard mathematical
      modeling practices mask the importance of parameters that control contact
      inhibition through scaling arguments. Furthermore, standard experimental
      protocols are insufficient to quantify the effects of contact inhibition because
      they focus on data describing early time, low-density dynamics only. Here we use
      the logistic growth equation as a caricature model of contact inhibition to make
      recommendations as to how to best mitigate these issues. Taking a Bayesian
      approach, we quantify the trade off between different features of experimental
      design and estimates of parameter uncertainty so that we can reformulate a
      standard cell proliferation assay to provide estimates of both the low-density
      intrinsic growth rate, lambda, and the carrying capacity density, K, which is a
      measure of contact inhibition.

PMID- 29032962
TI  - The impact of postoperative complications on health-related quality of life in
      older patients with rectal cancer; a prospective cohort study.
AB  - OBJECTIVES: As result of the aging population and increasing rectal cancer
      incidence, more older patients undergo treatment for rectal cancer. This study
      compares treatment course, postoperative complications, and quality of life (QOL)
      between older and younger patients with rectal cancer and evaluates the impact of
      postoperative complications on QOL in the elderly. MATERIALS AND METHODS:
      Patients with rectal cancer participating in a prospective colorectal cancer
      cohort and referred for radiotherapy between 2013 and 2016 were included. QOL was
      assessed with the cancer questionnaire of the European Organisation for Research
      and Treatment of Cancer (EORTC QLQ-C30) before treatment and at three, six, and
      twelve months. Outcomes were compared between older patients (>=70years) and
      younger patients (<70years) and stratified by presence of postoperative
      complications. RESULTS: In total, 115 (33%) older patients and 230 (67%) younger
      patients were included. Compared to younger patients, older patients underwent
      significantly more often short-course radiation with delayed surgery (6.1% and
      19.1% respectively) and less often chemoradiation (62.6% and 39.1% respectively),
      and were more likely to undergo a Hartmann procedure with permanent stoma (3.5%
      and 13.0% respectively) instead of sphincter-sparing surgery (43.9% and 29.6%
      respectively). Postoperative complication rates were similar (38.5% in older
      patients versus 34.7% in younger patients). Older patients had worse physical
      functioning at six and twelve months after diagnosis compared to younger
      patients. Presence of postoperative complications had a significant stronger
      impact on physical- and role functioning in older patients. CONCLUSION: Older
      patients undergo more often a tailored treatment approach for rectal cancer than
      younger patients. With this tailored approach, similar postoperative complication
      rates and QOL are achieved. However, postoperative complications have a larger
      negative impact on physical- and role functioning in older patients which
      indicates a need for better prediction of postoperative complications in the
      elderly.

PMID- 29032963
TI  - Exploring sex differences in diets and activity patterns through dental and
      skeletal studies in populations from ancient Corinth, Greece.
AB  - Sex and temporal differences are assessed in relation to dietary habits and
      activity patterns in three ancient populations from Corinth, Greece. The skeletal
      sample spans time from the Geometric to the Early Byzantine Period (9th c. BCE
      5th c. CE). Dental caries and tooth wear have been proven to be reliable dietary
      indicators. Similarly, spinal osteoarthritis, spinal facet remodeling and
      Schmorl's nodes, have been used to infer activity patterns.

PMID- 29032964
TI  - Response to letter re "In pursuit of the perfect penis: Hypospadias repair
      outcomes".

PMID- 29032965
TI  - Long term mortality in critically ill burn survivors: Methodological issues.

PMID- 29032966
TI  - Safety and efficacy of uninterrupted perioperative enteral feeding in pediatric
      burn patients.
AB  - INTRODUCTION: Burn injuries are a significant cause of morbidity. Early enteral
      nutrition has been shown to improve outcomes, however enteral nutrition is often
      held for procedures receiving general anesthesia. Limited data is available on
      uninterrupted perioperative nutrition in pediatric burn patients. METHODS: A
      single, American Burn Association verified burn center database was queried for
      patients <=18 years of age with >=15% total body surface area (TBSA) burn
      injuries who underwent surgeries with general anesthesia. Demographic and
      clinical details were analyzed comparing patients who were fed continuously and
      those with interrupted feeds. RESULTS: Thirty-one patients met inclusion
      criteria. Eighteen had continuous feeds and thirteen had interrupted feeds. We
      found perioperative enteral feeds safe as there were no aspiration events in
      these patients. Patients with interrupted feeds lost an average of 119.1kcal/kg
      and 1.4days of estimated energy needs. This was a 125% fall below metabolic
      needs. This loss was more pronounced with multiple operations and for patients
      <30kg. Patients with continuous feeds gained an average of 144.4kcal/kg and
      1.7days of estimated energy needs. These patients surpassed metabolic needs by
      173%. Again, this had the biggest impact in patients with multiple operations and
      those <30kg. CONCLUSIONS: The metabolic demands of burn patients are above most
      critically ill patients. To meet these demands, we implemented uninterrupted
      perioperative feeding. There were no aspiration events. Continuous feeds were an
      effective means to achieve caloric demands and moderate catabolic injury. We
      demonstrated safety and efficacy of uninterrupted perioperative feeding of
      pediatric burn patients.

PMID- 29032967
TI  - Occlusive drainage system for split-thickness skin graft: A prospective
      randomized controlled trial.

PMID- 29032968
TI  - Early intervention by Captopril does not improve wound healing of partial
      thickness burn wounds in a rat model.
AB  - The Renin Angiotensin System is involved in fibrotic pathologies in various
      organs such as heart, kidney and liver. Inhibition of this system by angiotensin
      converting enzyme antagonists, such as Captopril, has been shown beneficial
      effects on these pathologies. Captopril reduced the inflammatory reaction but
      also directly influenced the fibrotic process. Prolonged and excessive
      inflammatory response is a major cause of hypertrophic scar formation in burns.
      We therefore evaluated the effect of Captopril on the healing of partial
      thickness burn wounds in a rat model. Partial thickness contact burns were
      inflicted on the dorsum of the rats. The rats received either systemic or local
      treatment with Captopril. The inflammatory reaction and wound healing (scar)
      parameters were investigated and compared to control animals. In this study we
      could not detect positive effects of either administration route with Captopril
      on the inflammatory reaction, nor on wound healing parameters. The local
      treatment showed reduced wound closure in comparison to the systemic treatment
      and the control group. Early Captopril treatment of burn wounds did not show the
      beneficial effects that were reported for fibrotic disorders in other tissues. To
      influence the fibrotic response Captopril treatment at a later time point, e.g.
      during the remodeling phase, might still have beneficial effects.

PMID- 29032969
TI  - The effect of adipose derived stromal vascular fraction on stasis zone in an
      experimental burn model.
AB  - BACKGROUND: Stasis zone is the surrounding area of the coagulation zone which is
      an important part determining the extent of the necrosis in burn patients. In our
      study we aim to salvage the stasis zone by injecting adipose derived stromal
      vascular fraction (ADSVF). METHODS: Thermal injury was applied on dorsum of
      Sprague-Dawley rats (n=20) by the "comb burn" model as described previously. When
      the burn injury was established on Sprague-Dawley rats (30min); rat dorsum was
      separated into 2 equal parts consisting of 4 burn zones (3 stasis zone) on each
      pair. ADSVF cells harvested from inguinal fat pads of Sprague-Dawley rats (n=5)
      were injected on the right side while same amount of phosphate buffered saline
      (PBS) injected on the left side of the same animal. One week later, average vital
      tissue on the statis zone was determined by macroscopy, angiography and
      microscopy. Vascular density, inflammatory cell density, gradient of fibrosis and
      epithelial thickness were determined via immunohistochemical assay. RESULTS:
      Macroscopic stasis zone tissue viability (32+/-3.28%, 57+/-4.28%) (p<0.01),
      average number of vessels (10.28+/-1.28, 19.43+/-1.72) (p<0.01), capillary count
      (15.67+/-1.97, 25.35+/-2.15) (p<0.01) vascular density (1.55+/-0.38, 2.14+/-0.45)
      (p<0.01) epithelial thickness (0.014+/-0.009mm, 0.024+/-0.0011mm) were higher on
      ADSVF side. Fibrosis gradient (1.87+/-0.51, 1.50+/-0.43) (p<0.01) and
      inflammatory cell density (1.33+/-0.40, 1.20+/-0.32) (p<0.01) were higher on the
      PBS side. CONCLUSION: Macroscopic and microscopic findings determined that ADSVF
      has a statistically significant benefit for salvaging stasis zone on acute burn
      injuries.

PMID- 29032970
TI  - Platelet count: A predictor of sepsis and mortality in severe burns.
AB  - BACKGROUND: Platelet cells, or thrombocytes, have additional roles to
      haemostasis. After burn injury, platelet counts drop to a nadir at days 2-5 then
      rise to a peak between days 10-18. The nadir has previously been associated with
      mortality but there is currently no thorough investigation of its potential to
      predict sepsis in adults. The primary objective of this study is to assess
      whether platelet count can predict survival and sepsis in adults with severe burn
      injuries. METHODS AND FINDINGS: A retrospective cohort analysis of platelet count
      and other blood parameters in 145 burn patients with a TBSA greater than 20%.
      AUROC analysis revealed that the platelet count and rBaux score together produce
      moderate discrimination for survival at less than 24h after injury (AUROC=0.848,
      95%CI 0.765-0.930). Platelet count at day 3 combined with TBSA has a modest
      association with sepsis (AUROC=0.779, 95%CI 0.697-0.862). Multivariable Cox
      regression analysis revealed platelet peak was the strongest predictor of
      mortality. CONCLUSIONS: A reduced peak platelet count is a strong predictor of 50
      day mortality. Platelet count nadir may have some association with sepsis.

PMID- 29032971
TI  - The prevention strategies for the geographical belt of self-immolation.

PMID- 29032972
TI  - Long term cardiovascular impacts after burn and non-burn trauma: A comparative
      population-based study.
AB  - OBJECTIVE: To compare post-injury cardiovascular disease (CVD) hospital
      admissions experienced by burn patients with non-burn trauma patients and people
      with no record of injury, adjusting for socio-demographic, health and injury
      factors. METHODS: Linked hospital and death data were analysed for a cohort of
      burn patients (n=30,997) hospitalised in Western Australia during the period 1980
      2012 and age and gender frequency matched comparison cohorts (non-burn trauma:
      n=28,647; non-injured: n=123,399). The number and length of hospital stay for CVD
      admissions were used as outcome measures. Multivariate negative binomial
      regression was used to derive adjusted incidence rate ratios (IRR) and 95%
      confidence intervals (95%CI). Multivariate Cox regression models and hazard
      ratios (HR) were used to examine first time post-injury CVD admissions. RESULTS:
      The burn cohort had a higher rate of CVD (combined) admissions (IRR, 95%CI: 1.16:
      1.08-1.24) and spent longer in hospital (IRR, 95%CI: 1.37, 1.13-1.66) than the
      non-burn trauma cohort. Both the burn cohort (IRR, 95%CI: 1.50, 1.40-1.60) and
      the non-burn trauma cohort (IRR, 95%CI: 1.29, 1.21-1.37) had higher adjusted
      rates of post-injury CVD admissions compared with the non-injured cohort. The
      burn cohort (HR, 95%CI: 2.27, 1.70-3.02) and non-burn trauma cohort (HR, 95%CI:
      2.19, 1.66-2.87) experienced significantly elevated first time CVD admissions
      during the first 6 months after injury, decreasing in magnitude from 6 months to
      5 years after injury (HR, 95%CI: burn vs. non-injured; 1.31, 1.16-1.48; non-burn
      trauma vs. non-injured; 1.16, 1.03-1.31); no significant difference in incident
      admission rates was found beyond 5 years (HR, 95%CI: burn vs. non-injured; 0.99,
      0.92-1.07; non-burn trauma vs. non-injured; 1.00, 0.93-1.07). CONCLUSIONS: Burn
      and non-burn trauma patients experience elevated rates of post-injury CVD
      admissions for a prolonged period after the initial injury and are particularly
      at increased risk of incident CVD admissions during the first 5-years after the
      injury event. Detailed clinical data are required to help understand the
      underlying pathogenic pathways triggered by burn and non-burn trauma. This study
      identified treatment needs for injury patients, burn and non-burn, for a
      prolonged period after discharge.

PMID- 29032973
TI  - Epidemiology and socio-demographic risk factors of self-immolation: A systematic
      review and meta-analysis.
AB  - OBJECTIVE: Self-immolation or self-inflicted burn is the most tragic and violent
      method of suicide. The higher prevalence of this dramatic phenomenon in Iran is a
      serious social and health problem. In this study, we conducted a meta-analysis to
      combine the results from available studies to examine the epidemiology and socio
      demographic characteristics of individuals who attempted self-immolation in Iran.
      METHOD: Pertinent studies were identified by searching the electronic
      bibliographic databases including PubMed, Scopus, Science Direct, Iran Medex,
      Magiran, Medlib and Scientific Information Database (SID) (2000-October 2016).
      Meta-analysis was used to summarize the research results on socio-demographic
      risk factors of self-immolation in Iran. The STROBE checklist was used to assess
      quality of the study. The random effect model was employed in the meta-analysis
      to account for the observed heterogeneity among the selected studies. RESULTS:
      Twenty-nine studies (sample size=5717) were included in the meta-analysis. The
      estimated average age of individuals who attempted self-immolation was 27.31 (95%
      confidence interval [CI]: 25.81-28.81) years. Women account for 70% (95% CI: 64
      77) of all self-immolation attempts in Iran. Thirty-nine (95% CI: 34-43) per cent
      of all self-immolation were among singles. Nineteen (95% CI: 16-22) per cent of
      self-immolators had mental disorder. Meta-regression model showed that the
      average age of individuals who attempted self-immolation increased significantly
      over the period between 2000 to 2016 (P-value=0.006). CONCLUSIONS: Our study
      indicated that individuals who attempted self-immolation in Iran were mainly
      women, married and young adults.

PMID- 29032974
TI  - Prospective comparative evaluation study of Laser Doppler Imaging and thermal
      imaging in the assessment of burn depth.
AB  - INTRODUCTION: The accurate assessment of burn depth is challenging but crucial
      for surgical excision and tissue preservation. Laser Doppler Imaging (LDI) has
      gained increasing acceptance as a tool to aid depth assessment but its adoption
      is hampered by high costs, long scan times and limited portability. Thermal
      imaging is touted as a suitable alternative however few comparison studies have
      been done. METHODS: Sixteen burn patients with 52 regions of interests were
      analysed. Burn depth was determined using four methods LDI, thermal imaging,
      photographic and real-time clinical evaluation at day 1 and day 3. LDI flux and
      Delta T values were used for the prediction of outcomes (wound closure in <21
      days). Photographic clinical evaluation of burn depth was performed by 4 blinded
      burn surgeons. RESULTS: Accuracy of assessment methods were greater on post burn
      day 3 compared to day 0. Accuracies of LDI on post burn day 0 and 3 were 80.8%
      and 92.3% compared to 55.8% and 71.2% for thermal imaging and 62.5% and 71.6% for
      photographic clinical assessment. Real-time clinical examination had an accuracy
      of 88.5%. Thermal imaging scan times were significantly faster compared to LDI.
      DISCUSSION: LDI outperforms thermal imaging in terms of diagnostic accuracy of
      burn depth likely due to the susceptibility of thermal imaging to environmental
      factors.

PMID- 29032975
TI  - Comparison of non-surgical methods for the treatment of deep partial thickness
      skin burns of the hand.
AB  - This paper describes a randomized, controlled, parallel-group, single-center
      clinical trial designed to compare non surgical treatment methods of deep partial
      thickness skin burns of the hand. All patients were scanned with the Laser
      Doppler Imaging device to determine the depth of the burn wound. Viable
      keratinocytes sites were determined according to the established Perfusion Units
      (PU) measurement system. The trial enrolled 87 patients with hand burn wounds in
      the section of 260-600PU. Hand burn patients were divided into the following four
      groups: treated with hydrocolloid dressings; treated with mechanical debridement
      of monofilament polyester fibers pad and then applying silver sulfadiazine;
      treated with gauze dressings containing enzymatic collagenase preparation. The
      fourth group of patients was treated with silver sulfadiazine and gauze
      dressings. This group was considered as the control group. The wound healing
      status was assessed after 3, 7, 14 and 21 days. Burn scars and injured extremity
      function were assessed after six months according to the Vancouver Scar Scale and
      Disabilities of the Arm, Shoulder and Hand Outcome Measure. The fastest
      epithelialization of hand burn wounds was observed in the patients group treated
      with hydrocolloid dressings (15, 7 days, p<0,05). The patients of this group also
      had less scars and a better hand function.

PMID- 29032976
TI  - The application of 3D-printed transparent facemask for facial scar management and
      its biomechanical rationale.
AB  - INTRODUCTION: Deep facial burns leave conspicuous scar to the patients and affect
      their quality of life. Transparent facemask has been adopted for the prevention
      and treatment of facial hypertrophic scars for decades. Recently, with the
      advancement of 3D printing, the transparent facemask could facilitate the fitting
      of the facial contour. However, the effectiveness of the device and its
      biomechanical characteristics on pressure management of hypertrophic scar would
      need more objective evaluation. METHOD: A biomechanical model of the transparent
      3D-printed facemask was established through finite element analysis. Ten patients
      with extensive deep facial burns within 6 months were recruited for clinical
      study using 3D-printed facemask designed according to biomechanical model, and
      the interface pressure was measured on each patient. The patients in the
      treatment group (n=5) was provided with the 3D-printed transparent face mask soon
      after initial scar assessment, while the delayed treatment group (n=5) began the
      treatment one month after the initial scar assessment. The scar assessment was
      performed one month post intervention for both groups. RESULTS: The biomechanical
      modeling showed that the 3D, computer-generated facemask resulted in unbalanced
      pressure if design modifications were not incorporated to address these issues.
      The interface pressure between the facemask and patient's face was optimized
      through individualized design adjustments and the addition of silicone lining.
      After optimization of pressure through additional lining, the mean thickness and
      hardness of the scars of all 10 patients were decreased significantly after 1
      month of intervention. In the delayed treatment group, the mean thickness of the
      scars was increased within the month without intervention, but it was also
      decreased after intervention. CONCLUSION: Facemask design and the silicone lining
      are important to ensure adequate compression pressure of 3D-printed transparent
      facemask. The intervention using the 3D-printed facemask appeared to show its
      efficacy to control the thickness and hardness of the facial hypertrophic scars.

PMID- 29032978
TI  - Histological observation of hairless mice skin after exposure to Simulated Solar
      Light: Comparison between the histological findings with different methodologies
      and 3R principle correlations.
AB  - BACKGROUND: Albino hairless mouse (AHM) has been used as a biological model in
      photodermatology. However, the experimental landscape is diverse to follow and
      need particular attention. PURPOSE: Irradiation parameters were investigated for
      the development of a protocol to assess alterations in the AHM skin using
      Simulated Solar Light (SSL). The present study was compared with published
      articles (last 15 years) according to irradiation protocols, morphological
      findings to minimize animal suffering and UV exposure. MATERIALS AND METHODS:
      Three groups: Control (G1), experimental - sunburn (G2) and skin photodamage
      assay (G3). G2 were immobilized and exposed to SSL once for 15, 30 and 45min. G3
      were exposed to SSL, without immobilization, for 15min once a day for one week.
      The dorsal skin was analyzed using hematoxylin and eosin technique. RESULTS: G2
      displayed different sunburn degrees. Based on the profile of the observed
      morphological alterations, a 15min irradiation was chosen as the exposure time to
      expose G3, without immobilization, for 5 consecutive days. CONCLUSION: These
      conditions produced the same morphological changes in the AHM with a shorter
      solar exposure time, without immobilizing the animals but using environmental
      exposure fluences, conforming to 3R (reduction - refinement - replacement)
      recommendations.

PMID- 29032977
TI  - Analysis of factor XIa, factor IXa and tissue factor activity in burn patients.
AB  - INTRODUCTION: An elevated procoagulant activity observed in trauma patients is,
      in part, related to tissue factor (TF) located on blood cells and microparticles.
      However, analysis of trauma patient plasma indicates that there are other
      contributor(s) to the procoagulant activity. We hypothesize that factor (F)XIa
      and FIXa are responsible for an additional procoagulant activity in burn
      patients. METHODS: Multiple time-point plasma samples from 56 burn patients
      (total number of samples was 471; up to 20 time-points/patient collected in 3
      weeks following admission) were evaluated in a thrombin generation assay using
      inhibitory antibodies to TF, FIXa and FXIa. RESULTS: Due to the limited volume of
      some samples, not all were analyzed for all three proteins. At admission, 10 of
      53 patients (19%) had active TF, 53 of 55 (96%) had FXIa and 48 of 55 (87%) had
      FIXa in their plasma. 34 patients of 56 enrolled (61%) showed TF activity at one
      or more time-points. All patients had FXIa and 96% had FIXa at one or more time
      points. Overall, TF was observed in 99 of 455 samples analyzed (22%), FXIa in 424
      of 471 (90%) and FIXa in 244 of 471 (52%). The concentration of TF was relatively
      low and varied between 0 and 2.1pM, whereas that of FXIa was higher, exceeding
      100pM in some samples. The majority of samples with FIXa had it at sub-nanomolar
      concentrations. No TF, FXIa and FIXa activity was detected in plasma from healthy
      individuals. CONCLUSIONS: For the first time reported, the majority of plasma
      samples from burn patients have active FXIa and FIXa, with a significant fraction
      of them having active TF. The concentration of all three proteins varies in a
      wide range.

PMID- 29032979
TI  - A treatment algorithm for the management of intraoral burns: A narrative review.
AB  - Oral mucosa follows a distinctly different trajectory of wound healing than skin.
      Although there are contemporary guidelines regarding treatment of burns to the
      skin, there is no standard of care specific to intraoral burns. This narrative
      review proposes an evidence-based treatment algorithm for the management of
      intraoral burns. Data was collated through a comprehensive review of the
      literature and only included studies that have reported particular success with
      favorable short- and long-term prognoses. In order to critically appraise the
      strength of the treatment recommendations, the GRADE criteria was applied to each
      arm of the algorithm. The algorithm was initially subdivided into the four
      primary etiologies of intraoral burns - thermogenic, cryogenic, chemical,
      electrical. Our findings emphasize the importance of conservative modalities of
      intra-oral burn treatment.

PMID- 29032980
TI  - Management of finger deep burns: The interest of local flaps.
AB  - INTRODUCTION: The management of finger deep burns is still problematic for the
      surgeon. Due to the fineness and the thickness of the subcutaneous tissue, after
      excision there is an important risk of exposure of the underlying tissue like
      bone, nerve or tendons. Local flaps (random pattern flap and pedicle flap)
      allowed ensuring a good quality covering with a tissue with many advantages (good
      thickness, sensitivity). On the contrary of all other techniques, flaps can be
      used independently from the vascular quality of the wound bed. Despite those
      advantages, the literature is poor to report the experience of flap in the
      management of finger deep burn. MATERIAL AND METHODS: We report our experience in
      the use of such technique with a series of 49 flaps. The cohort consisted of 34
      patients (22 men and 12 women) who were treated in our unit between 2003 and
      2012. RESULTS: Of the 49 flaps made, 71,4% were homodactyl flaps. 22,5% were
      heterodactyl flaps and 6,1% were intermetacarpian (second space) flaps. The rate
      of success was 87,8%. We reviewed 16 patients out of 34 patients operated, 20 of
      the 49 flaps performed (40,8%). The patients were reviewed by an independent
      surgeon. The average follow-up at this consultation was 4,25+/-2,46 years. The
      monofilament test was positive for 17 flaps (85% of cases). For the Weber's test,
      we found a normal perception threshold for 11 flaps (55%), with an average test
      at 2,8mm (2-4mm). Normal motricity was found at the donor site in 14 of the 16
      patients evaluated for 18 of the 20 revised flaps (90% of cases). In terms of
      cosmetic result, the average overall score obtained at the patient's own
      evaluation was 0.85. That obtained by the evaluator was equal to 0.55, with no
      significant difference (scale range from 0 best results to 5 worse results).
      DISCUSSION: Hand and finger burns are frequent and benefit from rapid, high
      quality coverage, enabling early mobilization to combat secondary stiffness
      problems. The high success rate of our series, as well as the quality of the
      functional and cosmetic results obtained, demonstrate the reliability and the
      interest of the digital flaps.

PMID- 29032981
TI  - Nationwide web survey of pediatric scalds: Prevalence and the relationship with
      household vacuum flasks.
AB  - OBJECTIVE: To explore the prevalence of pediatric (0-72 months old) scalds, and
      to clarify its relationship with household vacuum flasks. METHODS: A cross
      sectional online survey based on the largest social media in China. Online
      questionnaire was pushed twice a day to our target respondents for successive
      seven days. We were authorized to gain, analyze and publish the information
      related to this research by the Sina & Weibo data center. RESULTS: Prevalence of
      pediatric scalds was 5.5%. Gender ratio (boy to girl) was 1.96:1. Toddlers (12-36
      months old) were the most susceptible age group (54.5%). Non-intentional water
      spill was the main causation (77.3%). An extremely low percent (7.1%) of the
      parents performed first-aid as described by the "RRICH" rule: water rinse -
      clothes remove - water immersion - clean cover - hospital. Scars developed in
      52.7% patients and 14.7% of them underwent reconstructive surgery. There were
      75.5% Chinese families using vacuum flasks in daily life, but only 6.1% families
      used the fastening device to avoid burns. CONCLUSION: Prevalence of pediatric
      scalds (0-72 months old) was rather high, which might be related to the extensive
      insecure usage of household vacuum flasks.

PMID- 29032982
TI  - The menace of self-immolation plaguing Asian nations.

PMID- 29032983
TI  - Early versus late surgical management of complicated appendicitis in children: A
      statewide database analysis with one-year follow-up.
AB  - BACKGROUND: Complicated appendicitis is common in children, yet the timing of
      surgical management remains controversial. Some support initial antibiotics with
      delayed operation whereas others support immediate operation. While a few
      randomized trials have evaluated this question, they have been small, single
      center trials with limited follow-up. We present a database analysis of outcomes
      in early versus late surgical management of complicated appendicitis with one
      year follow-up. METHODS: We conducted a retrospective review of children with
      complicated appendicitis presenting between 2000 and 2013, utilizing a New York
      State database. We compare children undergoing later versus early appendectomy
      with a primary outcome measure of any complication within one year as determined
      from ICD-9 codes. RESULTS: 8840 children were included in the analysis, 7708 of
      whom underwent early appendectomy. Patients with late appendectomy were
      significantly more likely to have at least one complication when compared to
      those undergoing early appendectomy (34.6% vs 26.7%, p<0.01). CONCLUSIONS: We
      present the first population-level study evaluating early versus late
      appendectomy in children with complicated appendicitis with a one-year follow-up
      period. Children undergoing late appendectomy were more likely to have a
      complication than those undergoing early appendectomy. These data corroborated
      previous studies supporting early operative management. LEVEL OF EVIDENCE: This
      study provides level III evidence of a treatment study.

PMID- 29032984
TI  - Immune response in Mansonella ozzardi infection modulated by IL-6/IL-10 axis in
      Amazon region of Brazil.
AB  - Mansonellosis is an endemic disease in the South and Central America. In Brazil,
      one of the etiological agents is Mansonella ozzardi. This filarial infection is
      yet poorly understood, with a controversial morbity, presenting since a
      oligosymptoms, malaria-like signs or without complaint in humans. The knowledge
      of the human immune response to microfilariae infection is limited mainly by
      different evolutionary cycles of the parasite in the host. In addition, the
      prevalence of this filarial parasite infection is high in several regions of
      Amazonas State. A cross-sectional study was conducted in an endemic area for
      microfilariae of M. ozzardi (MF) infection in the Amazonas State, Brazil.
      Proinflammatory and regulatory cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN
      gamma, and IL-17A) were measured in cryopreserved serum using the Cytometric Bead
      Array techniques (CBA) in 54 patients diagnosed with M. ozzardi infection and 55
      individuals without the infection were included in the study (Controls). The IL
      4, IL-6 and IL-10 level increased in infected patients with MF infection, while
      IL-17A increased in control only. When we compared controls to patients with high
      or low parasite load, the increased level of IL-6 and IL-10 were maintained. IL-6
      contributes to the proinflammatory activity and IL-10 modulates Th1, Th2 and Th17
      immune response. Furthermore, IL-4 was detected as a marker in the MF infection
      and MF patients with low parasite load, indicating the action of the Th2 cell
      response. The complex network of cytokines acting during M. ozzardi infection
      depends on a fine balance to determine a host protective effect or filarial
      persistence. Therefore, these results suggest that the immune response in MF
      infection is modulated by IL-6/IL-10 axis.

PMID- 29032985
TI  - DAMP-TLR-cytokine axis dictates the fate of tumor.
AB  - Random mutations leading to loss of cell cycle control is not a rare occurrence
      in an organism but the mutated cells are recognized and eliminated preventing the
      development of a tumor. These potentially tumorigenic cells release damage
      associated molecular patterns (DAMPs), which are recognized by toll-like
      receptors (TLRs) on macrophages and dendritic cells. The initial TLR-DAMP
      interactions lead to different responses such as altered antigen presentation and
      cytokine release that directly affect T cell activation and removal of the
      tumorigenic cells. The indirect effects of TLR-DAMP interaction include chemokine
      directed altered T cell trafficking, angiogenesis for both T cell infiltration
      and tumor cell metastasis, and alteration of intra-tumoral milieu contributing to
      the development of tumor cells heterogeneity. Thus, the initial TLR-DAMP
      interaction has a set of local effects that modulate tumor cell growth and
      heterogeneity and a disseminating set of central effects that dynamically affect
      T cell trafficking and functions. Herein, we argue that the DAMP-TLR-cytokine
      axis in the tumor microenvironment serves as the mainstay that orchestrates and
      regulates the pro- and anti-tumor elements which dynamically interact between
      themselves eventuating in tumor regression or growth. The knowledge of this TLR
      based immuno-surveillance framework is a key to developing a novel immunotherapy
      against cancer.

PMID- 29032986
TI  - Mycobacterium tuberculosis strains induce strain-specific cytokine and chemokine
      response in pulmonary epithelial cells.
AB  - M. tuberculosis F15/LAM4/KZN has been associated with high transmission rates of
      drug resistant tuberculosis in the KwaZulu-Natal province of South Africa. The
      current study elucidated the cytokine/chemokine responses induced by
      representatives of the F15/LAM4/KZN and other dominant strain families in
      pulmonary epithelial cells. Multiplex cytokine analyses were performed at 24, 48
      and 72h post infection of the A549 pulmonary epithelial cell line with the
      F15/LAM4/KZN, F28, F11, Beijing, Unique and H37Rv strains at an MOI of ~10:1.
      Twenty-three anti- and pro-inflammatory cytokines/chemokines were detected at all
      time intervals. Significantly high concentrations of IL-6, IFN-gamma, TNF-alpha
      and G-CSF at 48h, and IL-8, IFN-gamma, TNF-alpha, G-CSF and GM-CSF at 72h, were
      induced by the F28 and F15/LAM4/KZN strains, respectively. Lower levels of
      cytokines/chemokines were induced by either the Beijing or Unique strains at all
      three time intervals. All strains induced up-regulation of pathogen recognition
      receptors (PRRs) (TLR3 and TLR5) while only the F15/LAM4/KZN, F11 and F28 strains
      induced significant differential expression of TLR2 compared to the Beijing,
      Unique and H37Rv strains. The low induction of cytokines in epithelial cells by
      the Beijing strain correlates with its previously reported hypervirulent
      properties. High concentrations of cytokines and chemokines required for early
      protection against M. tuberculosis infections induced by the F15/LAM4/KZN and F28
      strains suggests a lower virulence of these genotypes compared to the Beijing
      strain. These findings demonstrate the high diversity in host cytokine/chemokine
      response to early infection of pulmonary epithelial cells by different strains of
      M. tuberculosis.

PMID- 29032987
TI  - Virtual reconstruction of glenoid bone defects using a statistical shape model.
AB  - BACKGROUND: Description of the native shape of a glenoid helps surgeons to
      preoperatively plan the position of a shoulder implant. A statistical shape model
      (SSM) can be used to virtually reconstruct a glenoid bone defect and to predict
      the inclination, version, and center position of the native glenoid. An SSM-based
      reconstruction method has already been developed for acetabular bone
      reconstruction. The goal of this study was to evaluate the SSM-based method for
      the reconstruction of glenoid bone defects and the prediction of native anatomic
      parameters. METHODS: First, an SSM was created on the basis of 66 healthy
      scapulae. Then, artificial bone defects were created in all scapulae and
      reconstructed using the SSM-based reconstruction method. For each bone defect,
      the reconstructed surface was compared with the original surface. Furthermore,
      the inclination, version, and glenoid center point of the reconstructed surface
      were compared with the original parameters of each scapula. RESULTS: For small
      glenoid bone defects, the healthy surface of the glenoid was reconstructed with a
      root mean square error of 1.2 +/- 0.4 mm. Inclination, version, and glenoid
      center point were predicted with an accuracy of 2.4 degrees  +/- 2.1 degrees ,
      2.9 degrees  +/- 2.2 degrees , and 1.8 +/- 0.8 mm, respectively. DISCUSSION AND
      CONCLUSION: The SSM-based reconstruction method is able to accurately reconstruct
      the native glenoid surface and to predict the native anatomic parameters. Based
      on this outcome, statistical shape modeling can be considered a successful
      technique for use in the preoperative planning of shoulder arthroplasty.

PMID- 29032988
TI  - Clinical and radiographic outcomes after total shoulder arthroplasty with an
      anatomic press-fit short stem.
AB  - BACKGROUND: There is limited information assessing outcomes after total shoulder
      arthroplasty (TSA) with a press-fit short stem. The purpose of this study was to
      evaluate early clinical and radiographic outcomes and complications after TSA
      with an anatomic press-fit short stem. METHODS: We identified 118 TSAs completed
      with press-fit short stem and minimum 2-year follow-up; 85 of these patients had
      a grit-blasted (GB) short stem placed, whereas 33 patients had short stems with
      proximal porous coating (PPC). Shoulder function scores, active mobility
      measurements, and radiographs were assessed. RESULTS: The average age at surgery
      was 66.7 years, with average follow-up of 3 years. Significant improvements were
      noted for all shoulder function scores and active mobility measurements from the
      preoperative state to final follow-up (P < .001). There was no stem loosening in
      any patients with minimum 2-year follow-up; however, 3 female patients with GB
      stems had gross loosening of their humeral components before 1 year, 2 requiring
      revision. Radiolucent lines around the humeral component were found in 5.9%
      without evidence of loosening. Osseous resorption at the medial cortex was noted
      in 9.3%. Of patients with PPC stems, no patients were observed to have
      radiolucent lines compared with 8.2% in the GB group (P = .09). CONCLUSION: TSAs
      with anatomic press-fit short stem showed significant clinical improvements from
      the preoperative state to final short-term follow-up, with few complications and
      minimal radiographic changes. Lack of PPC may contribute to early loosening in
      patients with poor bone quality. The authors now use a short stem with PPC.

PMID- 29032990
TI  - Department of Error.

PMID- 29032989
TI  - Functional outcomes of distal triceps tendon repair comparing transosseous bone
      tunnels with suture anchor constructs.
AB  - BACKGROUND: Distal triceps tendon ruptures are relatively rare. Few studies have
      investigated functional outcomes after repair. There is no consensus on fixation
      methods for this injury. The purpose of this study was to compare the functional
      outcomes and the reoperation rates after distal triceps tendon repairs using
      transosseous tunnels and suture anchors. METHODS: A multicenter, retrospective
      review of all primary triceps repairs done between 2006 and 2015 was performed.
      Patients were included if they had a minimum of 2 years of follow-up.
      Intraoperative data recorded included repair method and number of anchors used
      when applicable. Patients were contacted for functional assessment with the Mayo
      Elbow Performance Score (MEPS). Postoperative complications were also queried.
      RESULTS: There were 56 cases of primary triceps repair identified in an all-male
      cohort. Average age at time of surgery was 52.7 years; 58.9% of patients had
      transosseous repair, and 41.1% had suture anchor repair. The average follow-up
      was 4.26 years. The average postoperative MEPS score for all patients was 94.
      There was no difference in MEPS outcomes based on construct type. Postoperative
      Disabilities of the Arm, Shoulder, and Hand scores had an overall average of
      4.81. A statistically significant difference was found, with the transosseous
      group averaging 2.98 points lower than the suture anchor group. This difference
      was not found to be clinically relevant. Only 4 patients had rerupture of the
      triceps requiring revision. CONCLUSIONS: Primary repair of distal triceps tendon
      ruptures yields good, durable patient outcomes with minimal rerupture regardless
      of repair construct.

PMID- 29032991
TI  - A milestone for palliative care and pain relief.

PMID- 29032992
TI  - Felicia Marie Knaul: advocate for better pain relief and palliative care.

PMID- 29032994
TI  - Department of Error.

PMID- 29032995
TI  - Department of Error.

PMID- 29032996
TI  - Department of Error.

PMID- 29032993
TI  - Alleviating the access abyss in palliative care and pain relief-an imperative of
      universal health coverage: the Lancet Commission report.

PMID- 29032997
TI  - Department of Error.

PMID- 29032998
TI  - Department of Error.

PMID- 29033000
TI  - [Proliferation of a basal cell carcinoma on a sebaceous nevus of the lower
      eyelid: Case report of a rare association].

PMID- 29032999
TI  - A prospective phase I comparison of toxicity and cosmesis outcomes of single
      fraction IORT and hypofractionated radiotherapy with IORT boost in early-stage
      breast cancer.
AB  - PURPOSE: Radiation therapy is proven to reduce local recurrence in patients with
      early-stage breast cancer. To reduce toxicity, treatment time, and improve
      accuracy, intraoperative radiation therapy was used as definitive treatment or as
      a boost. The study's objective was to compare the short-term toxicity and
      cosmesis of single-fraction (SF) IORT and hypofractionated radiotherapy with IORT
      boost (HfB) given as definitive treatment. METHODS AND MATERIALS: Between March
      2011 and December 2013, 57 patients aged 45-91 years and 24 patients aged 43-83
      years (total n = 81) with Stage 0-II were treated with SF or HfB (Mobetron,
      IntraOp Medical, Sunnyvale, CA). For SF treatment, 21 Gy was delivered using 4.5
      6 cm applicators with electron energies from 6 to 12 MeV. For HfB, an
      intraoperative boost of 10 Gy was delivered using 4-7 cm applicators with
      energies from 4 to 12 MeV followed by whole-breast radiation with 40.5 Gy over 15
      fractions. Toxicity was assessed at 2 weeks, 6 months, and 12 months per
      Radiation Therapy Oncology Group acute skin toxicity criteria and cosmesis.
      RESULTS: At 12 months, SF and HfB were well tolerated by all patients with no
      Grade 3+ toxicity. At 1 year, Grade-2 toxicity was resolved. Ninety-eight percent
      of SF patients and ninety percent of HfB patients had 0-1 grade toxicity. In the
      SF and HfB groups, 100% of patients had excellent or good cosmesis at 12-month
      followup interval. The SF exhibited a more favorable cosmesis with a higher
      percentage of excellent scores compared with HfB (80.4% vs. 45%; p = 0.0033).
      CONCLUSIONS: After breast conservation surgery, SF or HfB may be an option for
      patients with early-stage breast cancer compared to conventional external beam
      radiotherapy.

PMID- 29033001
TI  - The role of microRNAs in photodynamic therapy of cancer.
AB  - Photodynamic therapy (PDT) is a non-invasive treatment modality used in the
      management of both benign and malignant conditions. It involves the
      administration of a photosensitizing agent followed by local light irradiation,
      which activates the photosensitizer, resulting in tissue damage. An in-depth
      understanding of the molecular mechanisms and mediators of PDT is important, not
      only for appreciating how this treatment modality is effective, but also as an
      avenue for understanding potential shortfalls and untoward effects that can be
      managed or improved. MicroRNAs are a group of endogenous small non-coding
      regulatory molecules that play important roles in regulating several
      physiological processes and have been implicated in several pathologies including
      cancer. They have been found to regulate key cellular pathways and their aberrant
      expression highlights not only disease onset or progression, but is associated
      with therapy resistance and disease outcome. In the present review, we evaluate
      the role of microRNAs in PDT and dissect their function as effectors of PDT
      including the molecules they regulate. We also look at how miRNA signatures can
      be used as predictors of therapy response to PDT and what implications this may
      have in the treatment of patients with PDT.

PMID- 29033002
TI  - Fiber orientation effects in simple shearing of fibrous soft tissues.
AB  - Fiber-reinforcement is a common feature of many soft biological tissues.
      Continuum mechanics modeling of the mechanical response of such tissues using
      transversely isotropic hyperelasticity is now well developed. The fundamental
      deformation of simple shear within this framework is examined here. It is well
      known that the normal stress effect characteristic of nonlinear elasticity plays
      a crucial role in maintaining a homogeneous deformation state in the bulk of the
      specimen. Here we consider the effect of anisotropy and fiber-orientation on the
      shear and normal stresses. It is shown that the confining traction that needs to
      be applied to the top and bottom faces of a block in order to maintain simple
      shear can be compressive or tensile depending on the degree of anisotropy and on
      the angle of orientation of the fibers. In the absence of such an applied
      traction, an unconfined sample tends to bulge outwards or contract inwards
      perpendicular to the direction of shear so that one has the possibility of both a
      positive or negative Poynting effect. The results are illustrated using
      experimental data obtained by other authors for porcine brain white matter. The
      general results obtained here are relevant to the development of accurate shear
      test protocols for the determination of constitutive properties of fibrous
      biological soft tissues.

PMID- 29033003
TI  - Clinicopathological parameters affecting nodal yields in patients with oral
      squamous cell carcinoma receiving selective neck dissection.
AB  - INTRODUCTION: Nodal yield has been demonstrated as a very promising marker for
      the prognostic outcome of patients with oral squamous cell carcinoma. However,
      studies on the importance of clinicopathological factors affecting the number of
      resected lymph nodes are rare, especially for patients without pathologically
      proven cervical lymph nodes. MATERIAL AND METHODS: Retrospective chart review of
      264 patients with treatment naive oral squamous cell carcinoma and
      histopathologically proven negative cervical lymph node status, who received
      selective neck dissection of levels I-III/IV. Exclusion criteria were neoadjuvant
      chemoradiotherapy, comprehensive or bilateral neck dissection, T4b
      classification, perioperative death, unresectable disease, synchronous
      malignancy, follow-up <3 months and inadequate information to correctly determine
      nodal yield. Statistical analysis was performed by using univariate and
      multivariate analysis. RESULTS: The mean nodal yield was 22.31 with a standard
      deviation of 16.01 and a mean number of 17 nodes. Gender (p = 0.018), age (p =
      0.03), tumor classification (p < 0.001) and perineural invasion (p = 0.012) were
      significantly associated with nodal yield. Multivariate analysis indicated T
      classification (p = 0.049) and age (p = 0.020) as independent factors. Nodal
      yield was significantly associated with locoregional recurrence (p = 0.041;
      Cutoff value = 17). CONCLUSION: Advanced age and T-classification independently
      affect lymph node yields in patients with oral squamous cell carcinoma. Hence,
      they have to be considered for interpretation of both nodal yield and recommended
      minimum lymph node counts. Furthermore, resection of more than 17 lymph nodes is
      associated with a significantly lower risk of locoregional recurrence.

PMID- 29033004
TI  - The role of schools in the diagnosis of ADHD.

PMID- 29033005
TI  - ADHD in children and young people: prevalence, care pathways, and service
      provision.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common childhood behavioural
      disorder. Systematic reviews indicate that the community prevalence globally is
      between 2% and 7%, with an average of around 5%. At least a further 5% of
      children have substantial difficulties with overactivity, inattention, and
      impulsivity that are just under the threshold to meet full diagnostic criteria
      for ADHD. Estimates of the administrative prevalence (clinically diagnosed or
      recorded) vary worldwide, and have been increasing over time. However, ADHD is
      still relatively under-recognised and underdiagnosed in most countries,
      particularly in girls and older children. ADHD often persists into adulthood and
      is a risk factor for other mental health disorders and negative outcomes,
      including educational underachievement, difficulties with employment and
      relationships, and criminality. The timely recognition and treatment of children
      with ADHD-type difficulties provides an opportunity to improve long-term
      outcomes. This Review includes a systematic review of the community and
      administrative prevalence of ADHD in children and adolescents, an overview of
      barriers to accessing care, a description of associated costs, and a discussion
      of evidence-based pathways for the delivery of clinical care, including a focus
      on key issues for two specific age groups-younger children (aged <=6 years) and
      adolescents requiring transition of care from child to adult services.

PMID- 29033006
TI  - Relative age within the school year and diagnosis of attention-deficit
      hyperactivity disorder: a nationwide population-based study.
AB  - BACKGROUND: Findings are mixed on the relationship between attention-deficit
      hyperactivity disorder (ADHD) and younger relative age in the school year. We
      aimed to investigate whether relative age is associated with ADHD diagnosis in a
      country where prescribing rates are low and whether any such association has
      changed over time or relates to comorbid disorders (eg, conduct disorder [CD],
      oppositional defiant disorder [ODD], or learning disorder [LD]). METHODS: We used
      nationwide population-based registers to identify all Finnish children born
      between Jan 1, 1991, and Dec 31, 2004, who were diagnosed with ADHD from age 7
      years onwards (age of starting school). We calculated incidence ratios to assess
      the inter-relations between relative age within the school year, age at ADHD
      diagnosis, and year of diagnosis (1998-2003 vs 2004-11). FINDINGS: Between Jan 1,
      1998, and Dec 31, 2011, 6136 children with ADHD were identified. Compared with
      the oldest children in the school year (ie, those born between January and
      April), the cumulative incidence of an ADHD diagnosis was greatest for the
      youngest children (ie, those born between September and December); for boys the
      incidence ratio was 1.26 (95% CI 1.18-1.35; p<0.0001) and for girls it was 1.31
      (1.12-1.54; p=0.0007). The association between relative age and age at ADHD
      diagnosis reflected children diagnosed before age 10 years, and the strength of
      this association increased during recent years (2004-11). Thus, compared with
      children born between January and April, for those born between May and August,
      the ADHD incidence ratio was 1.37 (95% CI 1.24-1.53; p<0.0001) and for those born
      between September and December, the incidence ratio was 1.64 (1.48-1.81;
      p<0.0001). The relative age effect was not accounted for by comorbid disorders
      such as CD, ODD, or LD. INTERPRETATION: In a health service system with low
      prescribing rates for ADHD, a younger relative age is associated with an
      increased likelihood of receiving a clinical diagnosis of ADHD. This effect has
      increased in recent years. Teachers, parents, and clinicians should take relative
      age into account when considering the possibility of ADHD in a child or
      encountering a child with a pre-existing diagnosis. FUNDING: Academy of Finland,
      Finnish Medical Foundation, Orion Pharma Foundation, Finnish Cultural Foundation.

PMID- 29033007
TI  - Anthropogenic factors influencing invasive ascidian establishment in natural
      environments.
AB  - Marine environments are constantly impacted by bioinvasions. Invasive ascidians
      (Chordata, Tunicata) are well-known for their ability to rapidly overgrow any
      available substrate. While the majority of studies have investigated the factors
      contributing to the successful establishment of ascidians on artificial
      substrates, the anthropogenic factors that contribute to such establishment on
      natural substrates have rarely been investigated. Here, we studied non-indigenous
      ascidians presence on natural substrate for the first time, using underwater
      field surveys at eight natural sites along the Israeli Mediterranean coast, in
      order to provide an analysis of factors assisting their establishment. The
      findings revealed that sites exposed to extended sewage-spill events experimented
      a reduction in native ascidian species. Understanding which factors alter
      ascidian population is essential for further monitoring efforts, to protect areas
      that are more susceptible to invasion, and for developing effective management
      tools to control further spread of invasive species in natural environments.

PMID- 29033009
TI  - Lead extraction - Aspects beyond the procedure.

PMID- 29033008
TI  - Safety and Long-Term Efficacy of AAV4 Gene Therapy in Patients with RPE65 Leber
      Congenital Amaurosis.
AB  - The aim of this study was the evaluation of the safety and efficacy of unilateral
      subretinal injection of the adeno-associated vector (AAV) serotypes 2 and 4
      (AAV2/4) RPE65-RPE65 vector in patients with Leber congenital amaurosis (LCA)
      associated with RPE65 gene deficiency. We evaluated ocular and general tolerance
      and visual function up to 1 year after vector administration in the most severely
      affected eye in nine patients with retinal degeneration associated with mutations
      in the RPE65 gene. Patients received either low (1.22 * 1010 to 2 * 1010 vector
      genomes [vg]) or high (between 3.27 * 1010 and 4.8 * 1010 vg) vector doses. An
      ancillary study, in which six of the original nine patients participated,
      extended the follow-up period to 2-3.5 years. All patients showed good
      ophthalmological and general tolerance to the rAAV2/4-RPE65-RPE65 vector. We
      observed a trend toward improved visual acuity in patients with nystagmus,
      stabilization and improvement of the visual field, and cortical activation along
      visual pathways during fMRI analysis. OCT analysis after vector administration
      revealed no retinal thinning, except in cases of macular detachment. Our findings
      show that the rAAV2/4.RPE65.RPE65 vector was well tolerated in nine patients with
      RPE65-associated LCA. Efficacy parameters varied between patients during follow
      up.

PMID- 29033010
TI  - Stethoscope: A short autobiography.

PMID- 29033011
TI  - Usefulness of positron emission tomography (PET)/contrast-enhanced computed
      tomography (CE-CT) in discriminating between malignant and benign intraductal
      papillary mucinous neoplasms (IPMNs).
AB  - BACKGROUND/OBJECTIVES: We evaluated the usefulness of positron emission
      tomography (PET)/contrast-enhanced computed tomography (CE-CT) in discriminating
      between malignant and benign intraductal papillary mucinous neoplasms (IPMNs).
      METHODS: PET/CE-CT imaging was conducted on 29 IPMN lesions, which subsequently
      underwent surgery. Preoperative findings on PET/CE-CT imaging were compared with
      the histological findings of the resected specimens to determine the diagnostic
      accuracy of PET/CE-CT imaging for evaluation of the differential diagnosis
      between benign and malignant IPMNs. RESULTS: The final diagnoses of the 29 IPMN
      lesions were 9 benign and 20 malignant. Overall, 18 of the 20 malignant cases
      were positive for FDG uptake, while 7 of 9 benign cases were negative. The
      sensitivity, specificity, and diagnostic accuracy for benign/malignant
      differentiation using FDG uptake as a marker were 90.0%, 77.8%, and 86.2%,
      respectively. When guideline-based high-risk findings were used as markers,
      sensitivity, specificity, and diagnostic accuracy for mural nodules were 50.0%,
      66.7%, and 55.2%, while they were 40.0%, 56%, and 48.3% for main duct dilatation,
      respectively. CONCLUSIONS: FDG uptake on PET is a useful new marker for
      malignancy in benign/malignant differentiation. Because PET/CE-CT imaging is a
      noninvasive imaging modality that can evaluate FDG uptake in addition to the
      conventional high-risk findings, we believe it should be the first-line method
      for determining therapeutic approaches to IPMN.

PMID- 29033013
TI  - Clinical Prognosis of Superior Versus Basal Segment Stage I Non-Small Cell Lung
      Cancer.
AB  - BACKGROUND: Despite its extensive size, variations in the clinicopathologic
      features of tumors in the lower lobe have been little studied. The present study
      investigated the prognostic differences in tumors originating from the superior
      and basal segments of the lower lobe in patients with non-small cell lung cancer.
      METHODS: Data of 134 patients who underwent lobectomy or segmentectomy with
      systematic nodal dissection for clinical stage I, radiologically solid-dominant,
      non-small cell lung cancer in the superior segment (n = 60) or basal segment (n =
      74) between April 2007 and December 2015 were retrospectively reviewed. Factors
      affecting survival were assessed by the Kaplan-Meier method and Cox regression
      analyses. RESULTS: Prognosis in the superior segment group was worse than that in
      the basal segment group (5-year overall survival rates 62.6% versus 89.9%, p =
      0.0072; and 5-year recurrence-free survival rates 54.4% versus 75.7%, p = 0.032).
      In multivariable Cox regression analysis, a superior segment tumor was an
      independent factor for poor overall survival (hazard ratio 3.33, 95% confidence
      interval: 1.22 to 13.5, p = 0.010) and recurrence-free survival (hazard ratio
      2.90, 95% confidence interval: 1.20 to 7.00, p = 0.008). The superior segment
      group tended to have more pathologic mediastinal lymph node metastases than the
      basal segment group (15.0% versus 5.4%, p = 0.080). CONCLUSIONS: Tumor location
      was a prognostic factor for clinical stage I non-small cell lung cancer in the
      lower lobe. Patients with superior segment tumors had worse prognosis than
      patients with basal segment tumors, with more metastases in mediastinal lymph
      nodes.

PMID- 29033012
TI  - Timeliness of Care and Lung Cancer Tumor-Stage Progression: How Long Can We Wait?
AB  - BACKGROUND: Timely care of lung cancer is presumed critical, yet clear evidence
      of stage progression with delays in care is lacking. We investigated the reasons
      for delays in treatment and the impact these delays have on tumor-stage
      progression. METHODS: We queried our retrospective database of 265 veterans who
      underwent cancer resection from 2005 to 2015. We extracted time intervals between
      nodule identification, diagnosis, and surgical resection; changes in nodule
      radiographic size over time; final pathologic staging; and reasons for delays in
      care. Pearson's correlation and Fisher's exact test were used to compare cancer
      growth and stage by time to treatment. RESULTS: Median time from referral to
      surgical evaluation was 11 days (interquartile range, 8 to 17). Median time from
      identification to therapeutic resection was 98 days (interquartile range, 66 to
      139), and from diagnosis to resection, 53 days (interquartile range, 35 to 77).
      Sixty-eight patients (26%) were diagnosed at resection; the remainder had
      preoperative tissue diagnoses. No significant correlation existed between tumor
      growth and time between nodule identification and resection, or between tumor
      growth and time between diagnosis and resection. Among 197 patients with
      preoperative diagnoses, 42% (83) had intervals longer than 60 days between
      diagnosis and resection. Most common reasons for delay were cardiac clearance,
      staging, and smoking cessation. Larger nodules had fewer days between
      identification and resection (p = 0.03). CONCLUSIONS: Evaluation, staging, and
      smoking cessation drive resection delays. The lack of association between tumor
      growth and time to treatment suggests other clinical or biological factors, not
      time alone, underlie growth risk. Until these factors are identified, delays to
      diagnosis and treatment should be minimized.

PMID- 29033014
TI  - Clinicopathologic Features of Submucosal Esophageal Squamous Cell Carcinoma.
AB  - BACKGROUND: The prognoses of submucosal esophageal squamous cell carcinoma
      patients vary. Patients with favorable prognoses may receive less invasive or
      nonsurgical interventions, whereas patients with poor prognoses or advanced
      esophageal cancer may require aggressive treatments. We sought to identify
      prognostic factors for patients with submucosal esophageal squamous cell
      carcinoma, focusing on lymph node metastasis and recurrence. METHODS: We included
      137 submucosal esophageal squamous cell carcinoma patients who had undergone
      transthoracic esophagectomy with systematic extended lymph node dissection.
      Submucosal tumors were classified as SM1, SM2, and SM3 according to the depth of
      invasion. Prognostic factors were determined by univariable and multivariable
      analyses. RESULTS: Lymph node metastasis was observed in 18.8%, 30.5%, and 50.0%
      of SM1, SM2, and SM3 cases, respectively. The overall 5-year recurrence rate was
      21.9%; the rates for SM1, SM2, and SM3 tumors were 9.4%, 18.6%, and 34.8%,
      respectively. The SM1 tumors all recurred locoregionally; distant metastasis
      occurred in SM2 and SM3 cases. The 5-year overall survival rates were 83%, 77%,
      and 59% for SM1, SM2, and SM3 cases, respectively. On univariable analysis, lymph
      node metastasis, depth of submucosal invasion (SM3 versus SM1/2), and tumor
      location (upper thoracic versus mid/lower thoracic) were poor prognostic factors
      for overall survival. Multivariable Cox regression analyses identified depth of
      submucosal invasion (hazard ratio 2.51, 95% confidence interval: 1.37 to 4.61)
      and tumor location (hazard ratio 2.43, 95% confidence interval: 1.18 to 4.63) as
      preoperative prognostic factors. CONCLUSIONS: Tumor location (upper thoracic) and
      infiltration (SM3) are the worse prognostic factors of submucosal esophageal
      squamous cell carcinoma, but lymph node metastasis is not a predictor of poorer
      prognosis.

PMID- 29033015
TI  - Analyzing Effectiveness of Routine Pleural Drainage After Nuss Procedure: A
      Randomized Study.
AB  - BACKGROUND: The routine use of postoperative pleural cavity drainage after the
      Nuss procedure is not widely accepted, and its limited use depends on experience.
      This study analyzed the influence of pleural drainage in the surgical treatment
      of patients with pectus excavatum on the prevention of pneumothorax and the
      efficacy of using drainage after a corrective operation. METHODS: From November
      2013 to May 2015, 103 consecutive patients with pectus excavatum, aged 11 to 39
      years, underwent surgical treatment by the Nuss procedure. Patients were
      prospectively randomized into two groups. In 58 patients, a 28F chest tube was
      routinely introduced into the right pleural cavity during procedure for 2
      consecutive days (group I). In the remaining 45 patients, the drain was not
      inserted (group II). RESULTS: No statistically significant differences were found
      between the study groups, including sex, age, body mass index, or clinical
      subjective and objective factors in the preoperative evaluation. Group II
      manifested more complications in the early postoperative period; however, this
      was not statistically significant (group I vs group II; p = 0.0725). Pneumothorax
      requiring additional chest tube placement was statistically significant (group I
      vs group II; p = 0.0230). Other complications were also more frequent among
      patients from group II, although this did not reach statistical significance.
      Follow up was 22.9 +/- 6.4 months. CONCLUSIONS: Routine drainage of the pleural
      cavity during the Nuss procedure significantly reduces the incidence of
      postoperative pneumothorax and should be considered as a routine procedure.

PMID- 29033016
TI  - Positron Emission Tomography in Thymic Tumors: Analysis Using a Prospective
      Research Database.
AB  - BACKGROUND: Positron emission tomography may have a role in the pretreatment
      workup of patients with thymic malignancies. This study was undertaken to
      determine the utility of the maximum standardized uptake value (SUVmax) in
      predicting histologic type and tumor stage in a large cohort of thymic epithelial
      tumors. METHODS: The large, multiinstitutional, prospective database of The
      International Thymic Malignancy Interest Group (ITMIG) was queried for the use of
      positron emission tomography in the pretreatment workup of patients with thymic
      tumors. Data analyzed included demographics, SUVmax, histologic tumor type, and
      tumor stage. The distribution of SUVmax according to histologic type and Masaoka
      Koga pathologic stage was determined, and the ability of SUVmax to predict these
      two variables was calculated using analysis of receiver operating characteristic
      curves. RESULTS: Since 2012, data from 926 patients with thymic malignancies were
      entered into the ITMIG prospective database, of which 154 had a reported value
      for SUVmax. The area under the receiver operating characteristic curve for SUVmax
      in predicting histologic type and pathologic stage was 0.79 (95% confidence
      interval, 0.70 to 0.88; p < 0.001) and 0.81 (95% confidence interval, 0.73 to
      0.88; p < 0.001), respectively. In addition, there was a significant relationship
      between SUVmax and histologic type (p < 0.001) as well as Masaoka-Koga pathologic
      stage (p < 0.001). CONCLUSIONS: Positron emission tomography has utility in
      predicting clinicopathologic features of thymic malignancies. These results may
      have clinical application in the pretreatment workup of patients with these rare
      tumors.

PMID- 29033017
TI  - Neurocognitive and Psychological Outcomes in Adults With Dextro-Transposition of
      the Great Arteries Corrected by the Arterial Switch Operation.
AB  - BACKGROUND: Neurodevelopmental impairments have frequently been described in
      children and adolescents with dextro-transposition of the great arteries (d-TGA).
      The arterial switch operation (ASO) to correct d-TGA has been used for more than
      30 years, and more than 90% of these patients now reach adulthood. However, very
      little is known about their long-term functional outcomes. The present study
      investigated neurocognitive outcomes and the prevalence of psychiatric disorders
      in adults with d-TGA corrected by ASO. METHODS: Neurocognitive functioning was
      comprehensively assessed (general intellectual functioning, language, attention,
      visual-spatial skills, executive functions, memory) in 67 adults (59.7% men) with
      d-TGA (aged 22.9 +/- 3.4 years) and in 43 healthy individuals. The prevalence of
      psychiatric disorders, including depression and anxiety, was evaluated using a
      structured diagnostic interview. We also analyzed patient- and operative-related
      risk factors associated with outcomes. RESULTS: Compared with the general
      population and the control group, adults with d-TGA displayed reduced performance
      in tasks assessing attention, visual-spatial skills, executive functions, and
      memory (all p < 0.05). Compared with controls, patients had also a higher
      lifetime prevalence of depression (43% vs 19%, p = 0.008) and anxiety disorders
      (54% vs 33%, p = 0.025). Predictors of long-term outcomes included gender and
      parental socioeconomic and educational status (all p < 0.05). CONCLUSIONS: Adults
      who have undergone a neonatal ASO to correct d-TGA have an increased risk of
      cognitive deficits and psychiatric disorders. Evaluation of long-term
      neuropsychological and psychosocial outcomes in early adulthood is a crucial step
      to anticipate for adapted treatment strategies in adults with congenital heart
      disease.

PMID- 29033018
TI  - Irradiated recycled plastic as a concrete additive for improved chemo-mechanical
      properties and lower carbon footprint.
AB  - Concrete production contributes heavily to greenhouse gas emissions, thus a need
      exists for the development of durable and sustainable concrete with a lower
      carbon footprint. This can be achieved when cement is partially replaced with
      another material, such as waste plastic, though normally with a tradeoff in
      compressive strength. This study discusses progress toward a high/medium strength
      concrete with a dense, cementitious matrix that contains an irradiated plastic
      additive, recovering the compressive strength while displacing concrete with
      waste materials to reduce greenhouse gas generation. Compressive strength tests
      showed that the addition of high dose (100kGy) irradiated plastic in multiple
      concretes resulted in increased compressive strength as compared to samples
      containing regular, non-irradiated plastic. This suggests that irradiating
      plastic at a high dose is a viable potential solution for regaining some of the
      strength that is lost when plastic is added to cement paste. X-ray Diffraction
      (XRD), Backscattered Electron Microscopy (BSE), and X-ray microtomography explain
      the mechanisms for strength retention when using irradiated plastic as a filler
      for cement paste. By partially replacing Portland cement with a recycled waste
      plastic, this design may have a potential to contribute to reduced carbon
      emissions when scaled to the level of mass concrete production.

PMID- 29033019
TI  - Processing of mycotoxin contaminated waste streams through anaerobic digestion.
AB  - Food and feed stocks heavily contaminated with mycotoxins are rendered unfit for
      consumption and therefore discarded as waste. Due to the lack of guidelines and
      in accordance with the prudent avoidance principle, these waste streams are often
      incinerated. For better valorization, these streams could be used as input for
      anaerobic digestion. However, the degradation of multiple mycotoxins during
      anaerobic digestion and their effect on the methane production is currently
      unknown. In batch tests spiked with mycotoxins, aflatoxin B1, ochratoxin A,
      deoxynivalenol, zearalenone and T-2 toxin were degraded for more than 90%. For
      mesophile and thermophile digestion respectively, fumonisin B1 was degraded for
      70% and 85%, and most ergot alkaloids for 64% and 98%. Neither biogas production,
      nor methane production were influenced by the presence of the mycotoxins.
      Subsequently, semi-continuous reactors fed with contaminated maize resulted in
      more than 99% degradation for all mycotoxins after 1.8 hydraulic retention time
      with stable biogas production and process parameters. This study shows that
      mycotoxin contaminated organic waste can be safely valorized to methane while the
      digestate is void of mycotoxin residues.

PMID- 29033020
TI  - The seasonal evolution of fruit, vegetable and yard wastes by mono, co and tri
      digestion at Hyderabad, Sindh Pakistan.
AB  - The contribution of biowastes in municipal solid waste (MSW) is increasing day by
      day and being dumped in open atmosphere along with other wastes in every city of
      Pakistan. This study was formulated to evaluate the feasibility of biowastes such
      as fruit, vegetable and yard wastes of different seasons individual and mixing at
      different ratios to optimize methane production at Hyderabad Sindh, Pakistan.
      Batch digestion of selected samples was conducted for 40 days under mesophilic
      condition. Methane yield of individual fruit, vegetable and yard wastes (FrVYW)
      of summer and winter season was obtained in the range of 0.36-0.40 L/g VS and
      0.39-0.44 L/g VS added respectively. The results of co-digestion of FrVYW of
      summer and winter season were observed in the range of 0.42-0.45 L/g VS added and
      0.46 to 0.54 L/g VS added respectively. The results of tri-digestion of FrVYW of
      summer and winter season were achieved in the range of 0.46-0.53 L/g VS added and
      0.56-0.62 L/g VS added respectively. Findings of study showed that methane
      production potential of tri-digestions were highest than all of others and that
      of co-digestion were higher than mono-digestion of FrVYW. Overall results of
      study concluded that tri-digestion of FrVYW at the equal blending ratio reported
      highest methane potential. Therefore, the study recommended that tri-digestion of
      FrVYW at equal mixing ratio is an optimal ratio for anaerobic digestion process
      to yield maximum methane production from FrVYW.

PMID- 29033021
TI  - [Smoking cessation and pregnancy].
AB  - Active and passive smoking during pregnancy induce several deleterious effects
      that may have a negative impact on pregnancy progress, fetus development and both
      mother and newborn health. Smoking cessation should be a rule for any woman as
      soon as the beginning of her pregnancy, or better in anticipation of a pregnancy
      when contraception is no more taken. Every caregiver must help every pregnant
      woman who smokes to quit smoking. Smoking cessation interventions in pregnant
      women must combine a psychological support (mainly with cognitive behavioral
      therapy) and nicotine replacement therapy, which can also be used during breast
      feeding. It is recommended to adjust the dosage of nicotine replacement therapy
      according to the symptoms of under or over dosage at the end of the first week of
      use. On the other hand, vareniclin and bupropion are contra-indicated during
      pregnancy or breast-feeding. Electronic cigarette is not advised during
      pregnancy. Prevention of smoking relapse in postpartum period is essential since
      a percentage as high as 50% of women having quit during their pregnancy resume
      smoking during the 6 months following delivery.

PMID- 29033022
TI  - [Fetal biometry: It is time for change].

PMID- 29033023
TI  - Outcomes of pediatric delayed facial palsy after head trauma.
AB  - OBJECTIVE: To analyze clinical outcomes of delayed facial palsy after head trauma
      in the pediatric population. METHODS: A total of 45 pediatric cases with delayed
      facial palsy after head trauma were conservatively or surgically treated in our
      hospital between January 2009 and January 2015, and they were followed up for one
      year after the corresponding treatment. The clinical data were collected and the
      outcomes of facial nerve were analyzed. RESULTS: During the one-year follow-up,
      33 cases (82.5%) completely recovered, and 5 cases (12.5%) recovered to Grade II
      among the 40 cases accepting conservative treatment. For the 5 surgically treated
      cases, 4 cases (80.0%) recovered to Grade I or Grade II, and one case recovered
      to Grade III. CONCLUSION: The outcomes of pediatric delayed facial palsy after
      head trauma were generally satisfactory.

PMID- 29033024
TI  - A Predictive Model for a Reputation-Based General Surgery Residency Match and a
      Novel Online Calculator.
AB  - OBJECTIVE: This study aimed to identify medical student characteristics that
      predict a successful categorical match into a general surgery residency and a
      match based upon Doximity program rankings. DESIGN: This was a retrospective
      study that analyzed academic and personal predictors of a successful general
      surgery residency match. SETTING: This study was set at the University of Alabama
      at Birmingham School of Medicine, a public medical school. PARTICIPANTS: This
      study included 173 fourth-year medical students at a public medical school who
      matched into general surgery residency programs. METHODS: Our cohort comprised
      students graduating from our institution between 2004 and 2015 that matched into
      preliminary or categorical general surgery positions. We collected academic
      variables and performed univariate analyses and logistic regression to examine
      the likelihood of specific match outcomes. RESULTS: Of 173 students, 132 (76%)
      matched into a categorical position and 41 (24%) matched into a preliminary
      position. Of all variables, clinical ranking quartile was most effective in
      predicting a categorical match (R2 = 0.35). Models for a match based upon
      Doximity ranking lacked the same predictive power. CONCLUSIONS: This research
      identifies students that are at risk for not matching into a categorical position
      and predicts competitiveness for certain programs. It provides a novel calculator
      to give applicants easily interpretable match probabilities.

PMID- 29033025
TI  - The clinical utility of immunoglobulin G4 in the evaluation of autoimmune
      pancreatitis and pancreatic adenocarcinoma.
AB  - BACKGROUND: Elevation in the serum immunoglobulin-G4 (IgG4) level has been used
      as a diagnostic marker to distinguish autoimmune pancreatitis (AIP) from
      pancreatic ductal adenocarcinoma (PDAC), but its true utility is ill-defined.
      This study evaluates the clinical utility of IgG4 in differentiating AIP from
      PDAC. METHODS: All patients evaluated in the hepatopancreaticobiliary surgery
      clinics with measured serum IgG4 were included. Patients were divided into normal
      IgG4 (<135 mg/dL) and elevated IgG4 (>=135 mg/dL) groups. The final diagnosis was
      determined by operative pathology when available or by clinical outcome. The
      sensitivity, specificity, PPV, and NPV of IgG4 for diagnosing AIP was assessed.
      RESULTS: Between 1997 and 2015, 298 patients were identified. Normal IgG4 levels
      were present in 85% of patients (254/298), while 15% (44/298) were elevated. The
      overall prevalence of AIP was 17% (52/298). The sensitivity and specificity of
      IgG4 for AIP was 67% and 96%, respectively; however, the PPV was only 80%,
      including a 9% occurrence of PDAC in patients with an elevated IgG4. CONCLUSION:
      In this study of selected patients who underwent IgG4 testing, 9% of elevated
      IgG4 patients had PDAC. The overreliance on IgG4 as diagnostic for AIP may lead
      to mis-diagnosis and delayed treatment for PDAC.

PMID- 29033026
TI  - Economic impact of rapid diagnostic methods in Clinical Microbiology: Price of
      the test or overall clinical impact.
AB  - The need to reduce the time it takes to establish a microbiological diagnosis and
      the emergence of new molecular microbiology and proteomic technologies has
      fuelled the development of rapid and point-of-care techniques, as well as the so
      called point-of-care laboratories. These laboratories are responsible for
      conducting both techniques partially to response to the outsourcing of the
      conventional hospital laboratories. Their introduction has not always been
      accompanied with economic studies that address their cost-effectiveness, cost
      benefit and cost-utility, but rather tend to be limited to the unit price of the
      test. The latter, influenced by the purchase procedure, does not usually have a
      regulated reference value in the same way that medicines do. The cost
      effectiveness studies that have recently been conducted on mass spectrometry in
      the diagnosis of bacteraemia and the use of antimicrobials have had the greatest
      clinical impact and may act as a model for future economic studies on rapid and
      point-of-care tests.

PMID- 29033028
TI  - The implications and applications of learning via instructions.
AB  - Whereas psychology knows a long tradition of studies that focused on the role of
      practice and training in acquiring new skills or knowledge, systematic studies
      into learning via instructions remain relatively scarce. This is surprising given
      the tremendous influence instructions have on human behavior and cognition. In
      recent years, however, a (re)new(ed) interest into learning via instructions
      resulted in new paradigms and findings that can inspire future research in this
      understudied domain. We offer a brief overview of the articles in this special
      issue, which present some of the latest empirical developments dedicated to
      unraveling the implications and applications of learning via instructions. The
      special issue offers insights into the dynamics underlying the assimilation of
      new instructions and highlights the strengths and limitations of what can be
      achieved on the basis of instructions. Furthermore, the different studies
      showcase various examples of recent methodological advances in testing the
      effects of instructions. Finally, this special issue shows how different fields
      in psychology share similar questions on the role of instructions in human
      behavior, suggesting that this topic should no longer be considered as a
      subsidiary of these different fields, but as a research field on its own.

PMID- 29033029
TI  - Corrigendum to "Comparison of three cognitive exams in cardiac arrest survivors"
      [Resuscitation 116 (2017) 98-104].

PMID- 29033030
TI  - How to use stem cells for repair in stroke patients.
AB  - Regenerative cell therapy is a promising therapeutic strategy in neurology, most
      notably to improve stroke recovery. Although tolerability and feasibility have
      apparently been validated, many questions remain as to what is the best type of
      cells to use, the best route and the post-stroke delay for administration. Two
      main strategies have currently emerged: intravenous injection of mesenchymal stem
      cells with systemic trophic support; and intracerebral grafting of neural stem
      cells with brain repair effects at the lesion site. Multicenter clinical trials
      have just begun and are starting to assess the efficacy of these treatments on
      functional recovery. However, experimental studies also need to be conducted in
      parallel to precisely identify the mechanisms of action regarding the
      pathophysiology of brain plasticity, notably when stroke occurs with
      comorbidities. Such studies should also evaluate the potential of cell grafting
      combined with injectable biomaterials.

PMID- 29033027
TI  - Anhedonia Following Early-Life Adversity Involves Aberrant Interaction of Reward
      and Anxiety Circuits and Is Reversed by Partial Silencing of Amygdala
      Corticotropin-Releasing Hormone Gene.
AB  - BACKGROUND: Anhedonia, the diminished ability to experience pleasure, is an
      important dimensional entity linked to depression, schizophrenia, and other
      emotional disorders, but its origins and mechanisms are poorly understood. We
      have previously identified anhedonia, manifest as decreased sucrose preference
      and social play, in adolescent male rats that experienced chronic early-life
      adversity/stress (CES). Here we probed the molecular, cellular, and circuit
      processes underlying CES-induced anhedonia and tested them mechanistically.
      METHODS: We examined functional brain circuits and neuronal populations activated
      by social play in adolescent CES and control rats. Structural connectivity
      between stress- and reward-related networks was probed using high-resolution
      diffusion tensor imaging, and cellular/regional activation was probed using c
      Fos. We employed viral-genetic approaches to reduce corticotropin-releasing
      hormone (Crh) expression in the central nucleus of the amygdala in anhedonic
      rats, and tested for anhedonia reversal in the same animals. RESULTS: Sucrose
      preference was reduced in adolescent CES rats. Social play, generally considered
      an independent measure of pleasure, activated brain regions involved in reward
      circuitry in both control and CES groups. In CES rats, social play activated Crh
      expressing neurons in the central nucleus of the amygdala, typically involved in
      anxiety/fear, indicating aberrant functional connectivity of pleasure/reward and
      fear circuits. Diffusion tensor imaging tractography revealed increased
      structural connectivity of the amygdala to the medial prefrontal cortex in CES
      rats. Crh-short hairpin RNA, but not control short hairpin RNA, given into the
      central nucleus of the amygdala reversed CES-induced anhedonia without
      influencing other emotional measures. CONCLUSIONS: These findings robustly
      demonstrate aberrant interactions of stress and reward networks after early-life
      adversity and suggest mechanistic roles for Crh-expressing amygdala neurons in
      emotional deficits portending major neuropsychiatric disorders.

PMID- 29033031
TI  - The next challenges for optimal reperfusion in the era of mechanical
      thrombectomy.
AB  - The therapeutic management of acute ischemic stroke has changed tremendously over
      the past few years. Mechanical thrombectomy in addition to intravenous tissue
      plasminogen activator (t-PA) is currently the standard of care for patients
      experiencing acute ischemic stroke as a consequence of large vessel occlusion of
      the anterior circulation. Yet, despite strong evidence supporting such a
      therapeutic approach, several issues remain a source of debate, such as the need
      for intravenous t-PA, the optimal target for blood pressure levels and the
      opportunity for additional antithrombotic therapies to improve reperfusion. Given
      this perspective, periprocedural patient management is probably the next step to
      come with considerable changes.

PMID- 29033033
TI  - Corrections.

PMID- 29033035
TI  - An effective and safe vaccine will not be enough to prepare us for the next Ebola
      outbreak.

PMID- 29033036
TI  - Surgery for acute type A aortic dissection on oral anticoagulants: Being the
      dispatcher of a 911 call.

PMID- 29033032
TI  - Ring vaccination with rVSV-ZEBOV under expanded access in response to an outbreak
      of Ebola virus disease in Guinea, 2016: an operational and vaccine safety report.
AB  - BACKGROUND: In March, 2016, a flare-up of Ebola virus disease was reported in
      Guinea, and in response ring vaccination with the unlicensed rVSV-ZEBOV vaccine
      was introduced under expanded access, the first time that an Ebola vaccine has
      been used in an outbreak setting outside a clinical trial. Here we describe the
      safety of rVSV-ZEBOV candidate vaccine and operational feasibility of ring
      vaccination as a reactive strategy in a resource-limited rural setting. METHODS:
      Approval for expanded access and compassionate use was rapidly sought and
      obtained from relevant authorities. Vaccination teams and frozen vaccine were
      flown to the outbreak settings. Rings of contacts and contacts of contacts were
      defined and eligible individuals, who had given informed consent, were vaccinated
      and followed up for 21 days under good clinical practice conditions. FINDINGS:
      Between March 17 and April 21, 2016, 1510 individuals were vaccinated in four
      rings in Guinea, including 303 individuals aged between 6 years and 17 years and
      307 front-line workers. It took 10 days to vaccinate the first participant
      following the confirmation of the first case of Ebola virus disease. No secondary
      cases of Ebola virus disease occurred among the vaccinees. Adverse events
      following vaccination were reported in 47 (17%) 6-17 year olds (all mild) and 412
      (36%) adults (individuals older than 18 years; 98% were mild). Children reported
      fewer arthralgia events than adults (one [<1%] of 303 children vs 81 [7%] of 1207
      adults). No severe vaccine-related adverse events were reported. INTERPRETATION:
      The results show that a ring vaccination strategy can be rapidly and safely
      implemented at scale in response to Ebola virus disease outbreaks in rural
      settings. FUNDING: WHO, Gavi, and the World Food Programme.

PMID- 29033037
TI  - Takotsubo syndrome spreads its tentacles to congenital heart disease.

PMID- 29033038
TI  - Discussion.

PMID- 29033034
TI  - Antimicrobial resistance among children in sub-Saharan Africa.
AB  - Antimicrobial resistance is an important threat to international health.
      Therapeutic guidelines for empirical treatment of common life-threatening
      infections depend on available information regarding microbial aetiology and
      antimicrobial susceptibility, but sub-Saharan Africa lacks diagnostic capacity
      and antimicrobial resistance surveillance. We systematically reviewed studies of
      antimicrobial resistance among children in sub-Saharan Africa since 2005. 18 of
      1075 articles reviewed met inclusion criteria, providing data from 67 451
      invasive bacterial isolates from inconsistently defined populations in
      predominantly urban tertiary settings. Among neonates, Gram-negative organisms
      were the predominant cause of early-onset neonatal sepsis, with a high prevalence
      of extended-spectrum beta-lactamase-producing organisms. Gram-positive bacteria
      were responsible for a high proportion of infections among children beyond the
      neon atal period, with high reported prevalence of non-susceptibility to
      treatment advocated by the WHO therapeutic guidelines. There are few up-to-date
      or representative studies given the magnitude of the problem of antimicrobial
      resistance, especially regarding community-acquired infections. Research should
      focus on differentiating resistance in community-acquired versus hospital
      acquired infections, implementation of standardised reporting systems, and
      pragmatic clinical trials to assess the efficacy of alternative treatment
      regimens.

PMID- 29033039
TI  - Aldo R. Castaneda, MD, PhD: Recipient of the Lifetime Achievement Award and 74th
      president of The American Association for Thoracic Surgery.

PMID- 29033040
TI  - Beware of interrupting aortic-to-visceral collaterals!

PMID- 29033041
TI  - Short-term venoarterial extracorporeal membrane oxygenation for massive
      endobronchial hemorrhage after pulmonary endarterectomy.
AB  - OBJECTIVES: Pulmonary endarterectomy (PEA) is the only curative treatment option
      for patients with chronic thromboembolic pulmonary hypertension. Massive
      endobronchial bleeding that precludes weaning from cardiopulmonary bypass is an
      often-fatal complication of PEA. The aim of this study was to determine whether
      short-term extracorporeal membrane oxygenation (ECMO) is a safe and feasible
      procedure in patients with severe endobronchial bleeding. METHODS: From January
      2014 to December 2016, 396 patients (mean age 60 +/- 18 years, 54.5% male)
      underwent PEA in our department. Patients with severe endobronchial hemorrhage at
      the time of weaning from cardiopulmonary bypass (CPB) were switched to a heparin
      coated venoarterial ECMO circuit. After full-dose protamine administration to
      restore normal coagulation, weaning from ECMO was attempted in the operating
      room. RESULTS: In-hospital mortality was 2.3% (9/396 patients). Eight patients
      (2.0%) developed severe endobronchial bleeding classified as diffuse (n = 6) or
      localized (n = 2) by bronchoscopy. After reinstitution of CPB and subsequent
      switch to ECMO, the mean duration of ECMO support was 49 +/- 13 minutes, and all
      8 patients were weaned successfully from ECMO in the operating theater without
      further signs of endobronchial bleeding. One patient needed venovenous ECMO
      support for poor oxygenation 6 hours after surgery. Seven patients were
      discharged after a prolonged postoperative stay of 17.6 +/- 4.1 days. One patient
      died. This new concept significantly reduced mortality compared with previous
      (2009-2013) ECMO support (P = .0406). CONCLUSIONS: For patients with massive
      endobronchial bleeding after PEA, the intraoperative switch from CPB to
      venoarterial ECMO support with full-dose protamine administration is a new and
      potentially life-saving treatment concept.

PMID- 29033042
TI  - Ascending aortopathy with bicuspid aortic valve: Individualizing the threshold.

PMID- 29033044
TI  - Postoperative atrial fibrillation: Still in search of truth or a neglected
      complication?

PMID- 29033045
TI  - Finally, new conversations about video-assisted thoracoscopic surgical lobectomy.

PMID- 29033043
TI  - In vivo lung perfusion rehabilitates sepsis-induced lung injury.
AB  - BACKGROUND: Sepsis is the leading cause of lung injury in adults and can lead to
      acute respiratory distress syndrome (ARDS). Using a novel technique of isolated
      in vivo lung perfusion (IVLP), we hypothesized that normothermic IVLP will
      improve oxygenation and compliance in a porcine model of sepsis-induced lung
      injury. METHODS: Mature adult swine (n = 8) were administered lipopolysaccharide
      (LPS; 50 MUg/kg over 2 hours) via the external jugular vein, followed by
      sternotomy and central extracorporeal membrane oxygenation (ECMO) cannulation
      (right atrium to ascending aorta). The left pulmonary artery (inflow) and left
      superior and inferior pulmonary veins (outflow) were dissected out and cannulated
      to deliver isolated perfusion to the left lung. After 4 hours of normothermic
      IVLP with Steen solution, the left lung then underwent 4 hours of reperfusion
      after IVLP decannulation. Airway pressures and lung-specific pulmonary vein blood
      gases from the right lung (LPS control) and left lung (LPS + IVLP) of the same
      animal were compared. RESULTS: All animals demonstrated a significant reduction
      in the ratio of partial pressure of oxygen in arterial blood (PaO2)/fraction of
      inspired oxygen (FiO2) (P/F ratio) and total lung compliance at 2 hours after the
      start of LPS infusion (mean, 469 +/- 19.7 mm Hg vs 222.2 +/- 21.4 mm Hg; P <
      .0001). After reperfusion, 6 animals (75%) exhibited improved lung function,
      allowing for ECMO decannulation. Lung-specific oxygenation was superior in the
      left lung after 4 hours of reperfusion (mean, 310.5 +/- 54.7 mm Hg vs 201.1 +/-
      21.7 mm Hg; P = .01). Similarly, total lung compliance improved after IVLP of the
      left lung. The lung wet weight to dry weight ratio demonstrated reduced edema in
      rehabilitated left lungs (mean, 6.5 +/- 0.3 vs 7.5 +/- 0.4; P = .04).
      CONCLUSIONS: IVLP successfully rehabilitated LPS-injured lungs compared to ECMO
      support alone in this preclinical porcine model.

PMID- 29033046
TI  - Eschar removal by bromelain based enzymatic debridement (Nexobrid(r)) in burns:
      An European consensus.
AB  - Early debridement and/or eschar removal is regarded as a significant step in the
      treatment of deep partial and full thickness burns. It aims to control wound
      bioburden and allows early wound closure by conservative treatment or skin
      grafting. Preservation of viable dermis accompanied by early wound closure, is
      regarded as a necessary step to reduce scar related complication, e.g. functional
      limitations and/or unaesthetic scar formation. Aside from the classical
      techniques of surgical excision as tangential excision for eschar removal, hydro
      surgery, maggot therapy, laser, enzymatic debridement have been described as
      additional techniques in the burn surgeon's armamentarium. It is widely accepted
      that early eschar removal within 72h improves the outcome of burn wound treatment
      by reducing bacterial wound colonization, infection and length of hospital stay.
      In contrast, the right technique for eschar removal is still a matter of debate.
      There is increasing evidence that enzymatic debridement is a powerful tool to
      remove eschar in burn wounds, reducing blood loss, the need for autologous skin
      grafting and the number of wounds requiring surgical excision. In order to assess
      the role and clinical advantages of enzymatic debridement by a mixture of
      proteolytic enzymes enriched in Bromelain (Nexobrid(r)) beyond the scope of the
      literature and in view of users' experience, a European Consensus Meeting was
      scheduled. The aim was to provide statements for application, based on the mutual
      experience of applying enzymatic debridement in more than 500 adult and pediatric
      patients by the consensus panelists. Issues to be addressed were: indications,
      pain management and anesthesia, timing of application, technique of application,
      after-intervention care, skin grafting after enzymatic debridement, blood loss,
      training strategies and learning curve and areas of future research needs. Sixty
      eight (68) consensus statements were provided for the use of enzymatic
      debridement. The degree of consensus was remarkably high, with a unanimous
      consensus in 88.2% of statements, and lowest degree of consensus of 70% in only 3
      statements. This consensus document may serve as preliminary guideline for the
      use of enzymatic debridement with user-oriented recommendations until further
      evidence and systematic guidelines are available.

PMID- 29033047
TI  - Effect of Hemodialysis on Levels of High-Sensitivity Cardiac Troponin T.
AB  - Cardiac troponin (cTn) is essential for the diagnosis of an acute coronary
      syndrome (ACS). However, in end-stage renal disease (ESRD) baseline cTn levels
      are often elevated, and it is unknown whether the hemodialysis (HD) procedure
      affects cTn levels. This leaves clinicians unsure of how to interpret cTn in HD
      patients with cardiac ischemia. We therefore sought to determine if plasma levels
      of high-sensitivity cardiac troponin T (hs-cTnT) vary during or after HD
      treatment. We prospectively enrolled 10 chronic HD patients who were admitted to
      our institution. All participants were receiving thrice weekly HD before
      admission and were medically stable. Those admitted for ACS or to critical care
      units were excluded. Baseline hs-cTnT was measured immediately before HD. For the
      subsequent 6 hours, hs-cTnT was measured every 2 hours and every 3 hours
      thereafter for a total collection period of 24 hours. A significant decline in
      mean hs-cTnT was noted with HD. During HD (2 hours after HD initiation), hs-cTnT
      decreased by 10.7% (confidence interval 5% to 17%). Immediately after HD (4 hours
      after HD initiation), a decline of 12% (confidence interval 5% to 19%) was
      observed. Thereafter hs-cTnT began to rise. Hs-cTnT levels returned to baseline
      by 11 hours after HD completion and remained stable for the reminder of the
      study. In conclusion, HD induces a short-lived negative bias in hs-cTnT. When
      measured for investigation of ACS, hs-cTnT concentration should be interpreted
      with respect to time of dialysis and specimen collection.

PMID- 29033048
TI  - Comparison of Outcome After Percutaneous Mitral Valve Repair With the MitraClip
      in Patients With Versus Without Atrial Fibrillation.
AB  - Percutaneous mitral valve repair with the MitraClip is an established treatment
      for patients with mitral regurgitation (MR) who are inoperable or at high risk
      for surgery. Atrial Fibrillation (AF) frequently coincides with MR, but only
      scarce data of the influence of AF on outcome after MitraClip is available. The
      aim of the current study was to compare the clinical outcome after MitraClip
      treatment in patients with versus without atrial fibrillation. Between January
      2009 and January 2016, all consecutive patients treated with a MitraClip in 5
      Dutch centers were included. Outcome measures were survival, symptoms, MR grade,
      and stroke incidence. In total, 618 patients were treated with a MitraClip.
      Patients with AF were older, had higher N-terminal B-type natriuretic peptide
      levels, more tricuspid regurgitation, less often coronary artery disease and a
      better left ventricular function. Survival of patients treated with the MitraClip
      was similar for patients with AF (82%) and without AF (non-AF; 85%) after 1 year
      (p = 0.30), but significantly different after 5-year follow-up (AF 34%; non-AF
      47%; p = 0.006). After 1 month, 64% of the patients with AF were in New York
      Heart Association class I or II, in contrast to 77% of the patients without AF (p
      = 0.001). The stroke incidence appeared not to be significantly different (AF
      1.8%; non-AF 1.0%; p = 0.40). In conclusion, patients with AF had similar 1-year
      survival, MR reduction, and stroke incidence compared with non-AF patients.
      However, MitraClip patients with AF had reduced long-term survival and remained
      more symptomatic compared with those without AF.

PMID- 29033049
TI  - Usefulness of CHADS2 and CHA2DS2-VASc Scores for Stroke Prediction in Patients
      With Cancer and Atrial Fibrillation.
AB  - Stroke prediction scores have not been validated in patients with cancer and
      atrial fibrillation (AF). We aimed to identify unique risk factors and evaluate
      validity of CHADS2 and CHA2DS2-VASc scores to predict risk of stroke and
      mortality. A retrospective review of all patients with cancer with pre-existing
      AF presenting from 2008 to 2014 was performed. Outcomes included ischemic stroke
      and mortality. Prognostic factors were identified with Fine and Gray regression
      for stroke and Cox proportional hazards analysis for survival. After excluding
      patients with hemorrhagic strokes, 2,037 patients were analyzed. Genitourinary
      cancers were the most common (29%) followed by gastrointestinal cancers (18%).
      Overall, 52% had CHADS2 >=2. At a median of 6.4 months, 74 patients (3.6%)
      developed an ischemic stroke. Increased CHADS2 score was associated with stroke
      (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.19 to 1.67; p <0.001).

PMID- 29033050
TI  - Temporal Trends in the Incidence, Prevalence, and Survival of Patients With
      Atrial Fibrillation From 2004 to 2016.
AB  - A growing epidemic of atrial fibrillation (AF) has been predicted, although no
      data on the AF burden has been reported for the United States since 2010. The
      objectives of this study were to (1) describe trends in AF incidence, prevalence,
      and postdiagnosis survival from 2004 to 2016 within a large health-care system
      and (2) extrapolate observed prevalence rates to the entire US population to
      estimate the national AF burden. This retrospective cohort study incorporates the
      patients and electronic medical record of the Geisinger Health System, an
      integrated health-care delivery system serving central and northeast
      Pennsylvania. Standardized incidence rates were calculated per 1,000 person-years
      by calendar year, and point prevalence rates estimated on July 1st of the
      respective years from 2004 to 2016. Rate ratios were estimated from Poisson
      regression as the annual relative change over time. A total of 464,363 patients
      met study inclusion criteria. Age- and sex-adjusted AF incidence rates increased
      over the study period: 4.7, 5.0, 5.8, and 6.2 in 2004, 2008, 2012, and 2016,
      respectively (rate ratio 1.03 per year, 95% confidence interval 1.02, 1.03). Age-
      and sex-adjusted prevalence rates increased consistently over time from 2.7%,
      3.0%, 3.4%, to 4.1% in 2004, 2008, 2012, and 2016, respectively. In 2004, an
      estimated 6.1 million Americans had diagnosed AF, increasing to 6.7, 7.8, and 9.3
      million in 2008, 2012, and 2016, respectively. Postdiagnosis survival has not
      improved in recent years. In conclusion, AF incidence and prevalence have
      increased steadily since 2004, whereas postdiagnosis survival has not improved.

PMID- 29033051
TI  - Genetics of restless legs syndrome: An update.
AB  - A major role of genetic factors in the risk of developing restless legs syndrome
      (RLS) is supported by the high frequency of positive family history of RLS in
      patients affected with this disease, and the higher concordance rates in
      monozygotic twins compared with dizygotic ones in twin studies. In this review we
      have focused on those reports describing inheritance patterns of RLS, genetic
      anticipation, the results of studies performed on positivity of family history of
      RLS, twin studies, linkage studies in familial RLS, genome-wide association
      studies (GWAS), exome sequencing studies, and case-control association studies on
      candidate genes in RLS. Although to date the causative gene(s) has(ve) not been
      definitively identified, a number of variants of several genes, most of them
      through GWAS, have been associated with RLS risk, the strongest candidates being
      variants of PTPRD, BTBD9, and MEIS1 genes. Despite results of several recent case
      control association studies which have suggested a possible contribution of heme
      oxygenase 1 (HMOX1) rs2071746 and vitamin D3 receptor (VDR) rs731236 variants, or
      the presence of allele 2 of the complex microsatellite repeat Rep1 within the
      alpha-synuclein (SNCA) gene promoter in modifying the risk for RLS, these studies
      need to be replicated in further studies involving different populations.

PMID- 29033052
TI  - Regular tachycardia despite Wenckebach atrioventricular conduction.
AB  - We present a 21-year-old woman status post orthotopic heart transplantation
      initially presenting with a regular narrow complex tachycardia at 159beats/min.
      With intravenous diltiazem the rhythm transitioned to a regular tachycardia at
      106beats/min, 2/3rd of the initial heart rate. We demonstrate this to be a novel
      description of 3:2second-degree Mobitz type I atrioventricular block (Wenckebach)
      with the absence of the hallmark regularly irregular (grouped beating) pattern.

PMID- 29033054
TI  - Temporary stages and motivational variables: Two complementary perspectives in
      the help-seeking process for mental disorders.
AB  - INTRODUCTION: Help-seeking for mental disorders is a complex process, which
      includes different temporary stages, and in which the motivational variables play
      an especially relevant role. However, there is a lack of instruments to evaluate
      in depth both the temporary and motivational variables involved in the help
      seeking process. This study aims to analyse in detail these two sets of
      variables, using a specific instrument designed for the purpose, to gain a better
      understanding of the process of treatment seeking. MATERIAL AND METHODS: A total
      of 152 patients seeking treatment in mental health outpatient clinics of the NHS
      were individually interviewed: 71 had Obsessive-Compulsive Disorder, 21 had
      Agoraphobia, 18 had Major Depressive Disorder), 20 had Anorexia Nervosa, and 22
      had Cocaine Dependence. The patients completed a structured interview assessing
      the help-seeking process. Disorder severity and quality of life was also
      assessed. RESULTS: The patients with agoraphobia and with major depression took
      significantly less time in recognising their mental health symptoms. Similarly,
      patients with major depression were faster in seeking professional help.
      Motivational variables were grouped in 3 sets: motivators for seeking treatment,
      related to the negative impact of symptoms on mood and to loss of control over
      symptoms; motivators for delaying treatment, related to minimisation of the
      disorder; and stigma-associated variables. CONCLUSIONS: The results support the
      importance of considering the different motivational variables involved in the
      several stages of the help-seeking process. The interview designed to that end
      has shown its usefulness in this endeavour.

PMID- 29033053
TI  - Identification and characterization of a novel recessive KCNQ1 mutation
      associated with Romano-Ward Long-QT syndrome in two Iranian families.
AB  - BACKGROUND: One of the foremost causes of sudden cardiac death in the young is an
      inherent cardiac arrhythmia known as Long-QT syndrome (LQTS). Whereas
      heterozygous mutations typically lead to the Romano-Ward type of LQTS, We have
      provided a further evidence for the recessive transmission of a novel KCNQ1 gene
      mutation in two consanguineous families for the first time in Iran. METHODS: Next
      generation sequencing, DNA Sanger sequencing and haplotype analysis were
      performed for genotype determination. Twelve different in silico tools were used
      for predicting the variant pathogenecity along with the family and population
      study. RESULTS: A novel recessive KCNQ1 variant (p.D564G) was revealed in none of
      the unrelated healthy individuals but four patients in two apparently unrelated
      families. The variant was classified as a likely pathogenic mutation by combining
      the resulted criteria for the changed amino acid. CONCLUSIONS: Identification of
      the novel mutation not only supports the genetic testing as a definitive
      diagnostic tool for detection of at risk family members, but also emphasizes its
      screening in Iranian LQTS patients as this mutation is very likely a founder
      mutation in Iran.

PMID- 29033055
TI  - Ambient endotoxin in PM10 and association with inflammatory activity, air
      pollutants, and meteorology, in Chitwan, Nepal.
AB  - BACKGROUND: Endotoxin associated with ambient PM (particulate matter) has been
      linked to adverse respiratory symptoms, but there have been few studies of
      ambient endotoxin and its association with co-pollutants and inflammation.
      OBJECTIVES: Our aim was to measure endotoxin associated with ambient PM10
      (particulate matter with aerodynamic diameter<10MUm) in summer 2016 at four
      locations in Chitwan, Nepal, and investigate its association with meteorology, co
      pollutants, and inflammatory activity. METHODS: PM10 concentrations were recorded
      and filter paper samples were collected using E-samplers; PM1, PM2.5, black
      carbon (BC), methane (CH4), and carbon monoxide (CO) were also measured. The
      Limulus amebocyte lysate (LAL) assay was used for endotoxin quantification and
      the nuclear factor kappa B (NFkappaB) activation assay to assess inflammatory
      activity. RESULTS: The mean concentration of PM10 at the different locations
      ranged from 136 to 189MUg/m3, and of endotoxin from 0.29 to 0.53EU/m3. Pollutant
      presence was positively correlated with endotoxin. Apart from relative humidity,
      meteorological variations had no significant impact on endotoxin concentration.
      NF-kappaB activity was negatively correlated with endotoxin concentration.
      CONCLUSIONS: To the best of our knowledge, this study provides the first
      measurements of ambient endotoxin associated with PM10 in Nepal. Endotoxin and co
      pollutants were positively associated indicating a similar source. Endotoxin was
      negatively correlated with inflammatory activity as a result of a time-limited
      forest fire event during the sampling period. Studies of co-pollutants suggested
      that the higher levels of endotoxin related to biomass burning were accompanied
      by increased levels of anti-inflammatory agents, which suppressed the endotoxin
      inflammatory effect.

PMID- 29033056
TI  - Nonfasting TG/HDL-C ratio seems a good predictor of MACE in CAD patients with
      statin therapy. Could it be a treatment target?

PMID- 29033057
TI  - Clinical inertia versus overtreatment in glycaemic management.

PMID- 29033058
TI  - 3D interdigitated electrode array in the microchannel free of reference and
      counter electrodes.
AB  - We demonstrate the three-dimensional (3D) interdigitated array (IDA) chip that
      operates without reference and counter electrodes, which are necessary components
      to apply enough potential to trigger the intended redox process, but used
      unwieldy for chip-based electrochemical detection. Using the electrode
      configuration, we propose a unique electrochemical system that is capable of
      controlling applied potential to a pair of working electrodes despite absence of
      reference and counter electrodes by fixing the electron transfer mediator on the
      electrodes in a microchannel. The electrochemical potential of the 2-electrode
      (2E) system is defined by the potential of the electron transfer mediator,
      poly(methylene green) (PMG), immobilized with poly(dopamine) (PDA) on the ITO
      surface by electropolymerization. The 3D IDA chip in the 2E system successfully
      acts as an electrochemical immunosensing platform. Creatine Kinase-MB in human
      serum was measured down to ~ pg / mL level. Therefore, the 3D IDA in the 2E
      system constitutes a simple and scalable platform that needs only nL level of
      sample volume for sensitive electrochemical detection in miniaturized multiplex
      immunoassay field.

PMID- 29033059
TI  - Structural integration and performance of inter-sectoral public health-related
      policy networks: An analysis across policy phases.
AB  - BACKGROUND: Inter-sectoral policy networks may be effective in addressing
      environmental determinants of health with interventions. However, contradictory
      results are reported on relations between structural network characteristics
      (i.e., composition and integration) and network performance, such as addressing
      environmental determinants of health. This study examines these relations in
      different phases of the policy process. METHODS: A multiple-case study was
      performed on four public health-related policy networks. Using a snowball method
      among network actors, overall and sub-networks per policy phase were identified
      and the policy sector of each actor was assigned. To operationalise the outcome
      variable, interventions were classified by the proportion of environmental
      determinants they addressed. RESULTS: In the overall networks, no relation was
      found between structural network characteristics and network performance. In most
      effective cases, the policy development sub-networks were characterised by
      integration with less interrelations between actors (low cohesion), more equally
      distributed distances between the actors (low closeness centralisation), and
      horizontal integration in inter-sectoral cliques. The most effective case had non
      public health central actors with less connections in all sub-networks.
      CONCLUSION: The results suggest that, to address environmental determinants of
      health, sub-networks should be inter-sectorally composed in the policy
      development rather than in the intervention development and implementation
      phases, and that policy development actors should have the opportunity to connect
      with other actors, without strong direction from a central actor.

PMID- 29033060
TI  - A review of international coverage and pricing strategies for personalized
      medicine and orphan drugs.
AB  - BACKGROUND: Personalized medicine and orphan drugs share many characteristics
      both target small patient populations, have uncertainties regarding efficacy and
      safety at payer submission, and frequently have high prices. Given personalized
      medicine's rising importance, this review summarizes international coverage and
      pricing strategies for personalized medicine and orphan drugs as well as their
      impact on therapy development incentives, payer budgets, and therapy access and
      utilization. METHODS: PubMed, Health Policy Reference Center, EconLit, Google
      Scholar, and references were searched through February 2017 for articles
      presenting primary data. RESULTS: Sixty-nine articles summarizing 42 countries'
      strategies were included. Therapy evaluation criteria varied between countries,
      as did patient cost-share. Payers primarily valued clinical effectiveness; cost
      was only considered by some. These differences result in inequities in orphan
      drug access, particularly in smaller and lower-income countries. The uncertain
      reimbursement process hinders diagnostic testing. Payer surveys identified lack
      of comparative effectiveness evidence as a chief complaint, while manufacturers
      sought more clarity on payer evidence requirements. Despite lack of strong
      evidence, orphan drugs largely receive positive coverage decisions, while
      personalized medicine diagnostics do not. CONCLUSIONS: As more personalized
      medicine and orphan drugs enter the market, registries can provide better quality
      evidence on their efficacy and safety. Payers need systematic assessment
      strategies that are communicated with more transparency. Further studies are
      necessary to compare the implications of different payer approaches.

PMID- 29033061
TI  - Predicting Vision-Related Disability in Glaucoma.
AB  - PURPOSE: To present a new methodology for investigating predictive factors
      associated with development of vision-related disability in glaucoma. DESIGN:
      Prospective, observational cohort study. PARTICIPANTS: Two hundred thirty-six
      patients with glaucoma followed up for an average of 4.3+/-1.5 years. METHODS:
      Vision-related disability was assessed by the 25-item National Eye Institute
      Visual Function Questionnaire (NEI VFQ-25) at baseline and at the end of follow
      up. A latent transition analysis model was used to categorize NEI VFQ-25 results
      and to estimate the probability of developing vision-related disability during
      follow-up. Patients were tested with standard automated perimetry (SAP) at 6
      month intervals, and evaluation of rates of visual field change was performed
      using mean sensitivity (MS) of the integrated binocular visual field. Baseline
      disease severity, rate of visual field loss, and duration of follow-up were
      investigated as predictive factors for development of disability during follow
      up. MAIN OUTCOME MEASURES: The relationship between baseline and rates of visual
      field deterioration and the probability of vision-related disability developing
      during follow-up. RESULTS: At baseline, 67 of 236 (28%) glaucoma patients were
      classified as disabled based on NEI VFQ-25 results, whereas 169 (72%) were
      classified as nondisabled. Patients classified as nondisabled at baseline had
      14.2% probability of disability developing during follow-up. Rates of visual
      field loss as estimated by integrated binocular MS were almost 4 times faster for
      those in whom disability developed versus those in whom it did not (-0.78+/-1.00
      dB/year vs. -0.20+/-0.47 dB/year, respectively; P < 0.001). In the multivariate
      model, each 1-dB lower baseline binocular MS was associated with 34% higher odds
      of disability developing over time (odds ratio [OR], 1.34; 95% confidence
      interval [CI], 1.06-1.70; P = 0.013). In addition, each 0.5-dB/year faster rate
      of loss of binocular MS during follow-up was associated with a more than 3.5
      times increase in the risk of disability developing (OR, 3.58; 95% CI, 1.56-8.23;
      P = 0.003). CONCLUSIONS: A new methodology for classification and analysis of
      change in patient-reported quality-of-life outcomes allowed construction of
      models for predicting vision-related disability in glaucoma.

PMID- 29033062
TI  - Ethical issues in global health engagement.
AB  - With an increasing number of clinicians participating in global health work, such
      engagement is now more than ever in need of critical ethical scrutiny. Exemplary
      initiatives in research, academics and publication, and other special
      considerations, provide potential approaches for overcoming ethical challenges in
      global health work. These methods demonstrate that successful global health work
      includes a commitment to foundational ethical principles such as trust, honesty,
      open communication and transparency, sustainability, capacity building, and
      appreciation for multiple perspectives - principles that surpass the traditional
      considerations of clinical practice. From this perspective, successful
      interventions to reduce neonatal and perinatal mortality must be strategically
      focused on building in-country capacity and sustainability.

PMID- 29033063
TI  - Factor analysis of symptom profile in early onset and late onset OCD.
AB  - This study aimed to assess the factor structure of early and late onset OCD.
      Additionally, cluster analysis was conducted in the same sample to assess the
      applicability of the factors. 345 participants were assessed with Yale Brown
      Obsessive Compulsive Scale symptom checklist. Patients were classified as early
      onset (onset of symptoms at age <= 18 years) and late onset (onset at age > 18
      years) OCD depending upon the age of onset of the symptoms. Factor analysis and
      cluster analysis of early-onset and late-onset OCD was conducted. The study
      sample comprised of 91 early onset and 245 late onset OCD subjects. Males were
      more common in the early onset group. Differences in the frequency of
      phenomenology related to contamination related, checking, repeating, counting and
      ordering/arranging compulsions were present across the early and late onset
      groups. Factor analysis of YBOCS revealed a 3 factor solution for both the
      groups, which largely concurred with each other. These factors were named as
      hoarding and symmetry (factor-1), contamination (factor-2) and aggressive, sexual
      and religious factor (factor-3). To conclude this study shows that factor
      structure of symptoms of OCD seems to be similar between early-onset and late
      onset OCD.

PMID- 29033064
TI  - Mathematical models and vaccination strategies.
AB  - Infection transmission is a complex and dynamic process, and is therefore
      difficult to assess. Consequently, mathematical models are a useful tool to
      understand any leverage on this transmission, such as vaccination. Models can
      provide guidance to implement an optimal vaccination campaign whether it concerns
      the fraction of the population or the age-group to be vaccinated. Mathematical
      models can also provide insights on counter-intuitive collateral effects of
      vaccination campaign, given the possibility that the overall benefits for the
      general population may hide deleterious effects on some sub-groups. As a large
      proportion of the population is now vaccinated, complex modelling taking into
      account individual and population heterogeneity and behaviour is necessary
      although challenging. But the most crucial aspect in the future of mathematical
      modelling still consists in obtaining precise and exhaustive data.

PMID- 29033065
TI  - Hospital-based collaboration for epidemiological investigation of vaccine safety:
      A potential solution for low and middle-income countries?

PMID- 29033066
TI  - Hydroadenocarcinoma of clear cells located in the breast.

PMID- 29033067
TI  - Multinodular esophageal leiomyomatosis: An uncommon cause of mediastinal mass.

PMID- 29033068
TI  - Treatment of the axila in breast cancer surgery: Systematic review of its impact
      on survival.
AB  - Sentinel lymph node biopsy and ACOSOG-Z0011 criteria have modified axillary
      treatment in breast cancer surgery. We performed a systematic review of studies
      assessing the impact of axillary treatment on survival. The search showed 6891
      potentially eligible items. Of them, 23 clinical trials and 12 meta-analyses
      published between 1980 and 2017 met the study criteria. The review revealed that
      axillary lymph node dissection (ALND) can be omitted in patients pN0 and pN1mic,
      without compromising survival. In patients pN1 it is proposed not to treat the
      axilla or replace ALND for axillary radiotherapy. The main limitations of this
      study are the inclusion of old tests that do not use therapeutic targets and lack
      of risk categorization of relapse. In conclusion, axillary treatment can be
      avoided in patients without metastatic involvement or micrometastases in the
      sentinel lymph node. However, there is no evidence to make a recommendation of
      axillary treatment in N1 patients, so individualized analysis of patient risk
      factors is needed.

PMID- 29033069
TI  - Surgery for hepatic hidatidosis. Risk factors and variables associated with
      postoperative morbidity. Overview of the existing evidence.
AB  - There are few publications related to postoperative morbidity in hepatic
      hydatidosis and these have mixed results. The aim of this study was to determine
      risk and protective factors of postoperative morbidity in patients operated on
      for hepatic hydatidosis. A comprehensive review was made of the evidence, based
      on systematic reviews, clinical analyses and observational studies, obtained from
      the Trip Database, BVS, SciELO, Cochrane Central Register of Controlled Trials,
      WoS, MEDLINE, EMBASE, SCOPUS, EBSCOhost, IBECS, ePORTUGUESe, LILACS and WHOLIS.
      1,087 related articles were identified; 69 fulfilled the selection criteria (2
      systematic reviews, 3 clinical trials and 64 observational studies). Age, history
      of previous surgery for hepatic hydatidosis, location in the hepatic center,
      existence of biliary communications and evolutionary complications of the cyst
      were identified as risk factors, and radical surgical techniques as protective
      factors. Risk and protective factors were identified; however, the studies are
      few and the quality moderate to low.

PMID- 29033070
TI  - Pleuroperitoneal communication in a patient with peritoneal dialysis: An
      interesting case for the surgeon.

PMID- 29033072
TI  - Gastroduodenal invagination secondary to gastric submucosal lipoma treated by
      laparoscopic transgastric excision.

PMID- 29033071
TI  - Secondary node analysis as an indicator for axillary lymphadenectomy in breast
      cancer patients.
AB  - INTRODUCTION: Currently, there is no agreement regarding if it would be necessary
      to perform an axillary lymph node dissection (ALND) in patients who have
      macrometastases in the sentinel lymph node (SLN). We studied the utility of the
      secondary node analysis (SN), defined as the following node after the SLN in an
      anatomical and lymphatic pathway, as a sign of malignant axillary involvement.
      METHODS: An observational, retrospective and multicentre study was designed to
      assess the utility of the SN as a sign of axillary involvement. Among 2273
      patients with breast cancer, a valid sample of 283 was obtained representing
      those who had the SN studied. Main endpoints of our study were: the SLN, the SN
      and the ALND histological pattern. Sensitivity, specificity and precision of the
      test were also calculated. RESULTS: SN test, in cases with positive SLN, has a
      sensitivity of 61.1%, a specificity of 78.7%, a positive predictive value of
      45.8% and a negative predictive value of 87.3% with a precision of 74.7%.
      CONCLUSION: The study of the SN together with the technique of the SLN allows a
      more precise staging of the axillary involvement, in patients with breast cancer,
      than just the SLN technique.

PMID- 29033073
TI  - Surgical Treatment of Supraclavicular and Internal Mammary Recurrence of Breast
      Cancer.

PMID- 29033074
TI  - Potentially active spoilage bacteria community during the storage of vacuum
      packaged beefsteaks treated with aqueous ozone and electrolyzed water.
AB  - The microbial contamination that occurs during the slaughtering process and
      during handling of the meat results in a shortening of the shelf-life of meat. In
      this study, which has had the aim of extending the shelf life of beefsteaks,
      pilot-scale treatments were carried out with aqueous ozone (AO) and electrolyzed
      water (EW) before vacuum packaging (VP). The development of the potentially
      active microbiota and the associated volatilome were followed over 15days of
      storage under refrigerated conditions (4 degrees C), in order to define the
      potential long-term effects of the treatments and storage condition on
      microbiota. The targeted RNA-based amplicon sequencing identified Pseudomonas
      fragi as the most frequent species before and after the treatments with AO and
      EW, as well as in the untreated control. The tested treatments did not reduce the
      overall presence of this species, but they affected the intra-species
      distribution of its oligotypes, albeit slightly. With the progression of the
      refrigerated storage and the reduction of the oxygen availability, Lactobacillus
      sakei, Leuconostoc gasicomitatum and Lactococcus piscium became the dominant,
      potentially active, beef microbiota, as confirmed by microbiological data. When
      the OTU abundances and volatilome were coupled, a significant association was
      observed between the organic acids, esters and aldehydes and these lactic acid
      bacteria species. In spite of the limited effectiveness of the treatments over
      the short and long term, this study has provided a detailed view of beef spoilage
      using RNA as the sequencing target, strengthening and confirming the current
      knowledge based on DNA-amplicon sequencing.

PMID- 29033075
TI  - Multi-drug resistant organism infections in a medical ICU: Association to
      clinical features and impact upon outcome.
AB  - OBJECTIVE: To define clinical features associated with Intensive Care Unit (ICU)
      infections caused by multi-drug resistant organisms (MDRO) and their impact on
      patient outcome. DESIGN: A single-center, retrospective case-control study was
      carried out between January 2010 and May 2010. SETTING: A medical ICU (MICU) in
      the United States. PATIENTS: The study included a total of 127 MDRO-positive
      patients and 186 MDRO-negative patients. INTERVENTIONS: No interventions were
      carried out. RESULTS: Out of a total of 313 patients, MDROs were present in 127
      (41.7%). Based on the multivariate analysis, only infection as a cause of
      admission [OR 3.3 (1.9-5.8)]), total days of ventilation [OR 1.07 (1.01-1.12)],
      total days in hospital [OR 1.04 (1.01-1.07)], immunosuppression [OR 2.04 (1.2
      3.5)], a history of hyperlipidemia [OR 2.2 (1.2-3.8)], surgical history [OR 1.82
      (1.05-3.14)] and age [OR 1.02 (1.00-1.04)] were identified as clinical factors
      independently associated to MDROs, while the Caucasian race was negatively
      associated to MDROs. The distribution of days on ventilation, days in hospital
      and days of antibiotic treatment prior to infection differed between the MDRO
      positive and MDRO-negative groups. The MDRO-positive patients showed a greater
      median number of days in hospital and days of antibiotic treatment before
      infection, with a greater median number of days in hospital, days of antibiotic
      treatment and days of ventilation after infection, compared to the MDRO-negative
      patients. The mortality rate was not significantly different between the two
      groups. Appropriate empirical antibiotic therapy was prescribed in 82% of the
      MDRO-positive cases - such treatment being started within 24h after onset of the
      infection in 68.5% of the cases. CONCLUSION: Defining clinical factors associated
      with MDRO infections and administering timely and appropriate empirical
      antibiotic therapy may help reduce the mortality associated with these
      infections. In our hospital we did not withhold broad spectrum drugs as empirical
      therapy in patients with clinical features associated to MDRO infection. Our rate
      of appropriate empirical therapy was therefore high, which could explain the
      absence of excessive mortality in patients infected with MDROs.

PMID- 29033076
TI  - Letter to the editor concerning "The learning curve with a new cephalomedullary
      femoral nail".

PMID- 29033077
TI  - Regarding: Management of esophageal injuries secondary to trauma. Injury, 2017,
      48: 1735-1742.

PMID- 29033078
TI  - Trochanteric entry femoral nails yield better femoral version and lower revision
      rates-A large cohort multivariate regression analysis.

PMID- 29033079
TI  - Polytrauma patients in the Netherlands and the USA: A bi-institutional comparison
      of processes and outcomes of care.
AB  - BACKGROUND: Modern trauma systems differ worldwide, possibly leading to
      disparities in outcomes. We aim to compare characteristics and outcomes of blunt
      polytrauma patients admitted to two Level 1 Trauma Centers in the US (USTC) and
      the Netherlands (NTC). METHODS: For this retrospective study the records of 1367
      adult blunt trauma patients with an Injury Severity Score (ISS) >= 16 admitted
      between July 1, 2011 and December 31, 2013 (640 from NTC, 727 from USTC) were
      analysed. RESULTS: The USTC group had a higher Charlson Comorbidity Index (mean
      [standard deviation] 1.15 [2.2] vs. 1.73 [2.8], p<0.0001) and Injury Severity
      Score (median [interquartile range, IQR] 25 [17-29] vs. 21 [17-26], p<0.0001).
      The in-hospital mortality was similar in both centers (11% in USTC vs. 10% NTC),
      also after correction for baseline differences in patient population in a
      multivariable analysis (adjusted odds ratio 0.95, 95% confidence interval 0.61
      1.48, p=0.83). USTC patients had a longer Intensive Care Unit stay (median [IQR]
      4 [2-11] vs. 2 [2-7] days, p=0.006) but had a shorter hospital stay (median [IQR]
      6 [3-13] vs. 8 [4-16] days, p<0.0001). USTC patients were discharged more often
      to a rehabilitation center (47% vs 10%) and less often to home (46% vs. 66%,
      p<0.0001), and had a higher readmission rate (8% vs. 4%, p=0.01). CONCLUSION:
      Although several outcome parameters differ in two urban area trauma centers in
      the USA and the Netherlands, the quality of care for trauma patients, measured as
      survival, is equal. Other outcomes varied between both trauma centers, suggesting
      that differences in local policies and processes do influence the care system,
      but not so much the quality of care as reflected by survival.

PMID- 29033080
TI  - Reconstitution of Th17, Tc17 and Treg cells after paediatric haematopoietic stem
      cell transplantation: Impact of interleukin-7.
AB  - Successful reconstitution of T lymphocytes after allogeneic haematopoietic stem
      cell transplantation (HSCT) is needed to establish the graft-versus-leukaemia
      effect and an effective anti-microbial defense, but the ratio between
      functionally different T-cell subsets needs to be balanced to avoid graft-versus
      host disease (GVHD). IL-7 is essential for T-cell generation in the thymus and
      peripheral T-cell homeostasis. High IL-7 levels have been associated with
      impaired T-cell reconstitution, increased risk of acute GVHD and treatment
      related mortality, but the underlying cellular mechanisms behind these
      associations have not been investigated previously. We hypothesized that
      increased levels of IL-7 post-transplant alters the balance between immune
      regulatory T cell subsets during the post-transplant lymphocyte recovery towards
      a more pro-inflammatory profile. We quantified Th17 cells, Tc17 cells and Tregs
      in 29 children following HSCT. Th17 cell and Treg counts rose significantly from
      day +90 to +180 post-HSCT, and prior acute GVHD was associated with significant
      changes in the concentration of Tregs (9.4*106/L vs. 1.3*106/L, P=0.0052) and the
      Th17/Treg ratio (1.5 vs. 4.2, P=0.025). The plasma level of IL-7 at day +90
      correlated inversely with Th17 cell counts (rs=-0.65, P=0.0002) and the
      proportion of Tc17 cells (rs=0.64, P=0.0005) at day +90, but not with Tregs.
      Furthermore, high IL-7 levels at day +7 were predictive of a less naive T-cell
      phenotype at day +90. These findings add further evidence that IL-7 is a key
      regulatory factor that may tune the balance between functionally different T-cell
      subsets following HSCT.

PMID- 29033081
TI  - A Cone-beam Computed Tomographic Study of Apical Surgery-related Morphological
      Characteristics of the Distolingual Root in 3-rooted Mandibular First Molars in a
      Chinese Population.
AB  - INTRODUCTION: Apical surgery on the separate distolingual (DL) root of a 3-rooted
      mandibular first molar is thought to be difficult because DL roots are always
      severely curved, small, and shorter than distobuccal (DB) roots, and they are
      located far from the buccal cortical bone. The purpose of this study was to use
      cone-beam computed tomographic images to investigate the apical surgery-related
      morphological characteristics of DL roots in a Chinese population. METHODS: The
      screening process identified 83 subjects with 128 mandibular first molars with
      separate DL roots. The degree of root canal curvature was measured in the
      mesiodistal (MD) and buccolingual (BL) planes using the Schneider method.
      Distances were measured from the DL root apex to the buccal cortical bone, to the
      buccal cortical bone opposite the DB root apex, and to the buccal cortical bone
      opposite the mesiobuccal (MB) root apex. The lengths of the remaining DB, MB, and
      DL roots were measured after resection of 3 mm of the DL apical root. Angulations
      of the DL root canal were determined before and after DL apical root resection.
      RESULTS: The teeth were classified into 3 types: type I, straight in the MD and
      BL planes; type II, straight in the MD plane and curved in the BL plane; and type
      III, curved in the MD and BL planes. Only 5 molars (3.9%) were classified as type
      I, whereas 52 (40.6%) molars were type II and 71 (55.5%) molars were type III.
      The type I DL root has a significantly shorter length and longer distance from
      the DL root apex to the buccal cortical bone than type II and III roots (P <
      .05). The distance from the DL root apex to the buccal cortical bone opposite the
      MB root apex is significantly longer than the distance to the buccal cortical
      bone opposite the DB root apex in types I and II (P < .05), whereas the distance
      is nearly equal for type III. The angulations for root-end preparation of types
      II and III DL roots vary from 57.5 degrees  to 129.1 degrees  and from 55.8
      degrees  to 128.1 degrees , respectively. CONCLUSIONS: A new classification was
      proposed for DL roots in 3-rooted mandibular first molars based on the root canal
      curvature. Type I is unsuitable for apical surgery. Access to the type II DL root
      apex should be through the DB root apex, whereas access to the type III DL root
      apex through the MB root apex is more feasible. Apical surgery on types II and
      III DL roots may be accomplished when the depth of the root-end preparation is
      reasonably reduced, and fine and personalized angulated ultrasonic retro tips are
      used.

PMID- 29033082
TI  - Root Canal Morphology Evaluation of Central and Lateral Mandibular Incisors Using
      Cone-beam Computed Tomography in an Israeli Population.
AB  - INTRODUCTION: Central and lateral mandibular incisors usually have 1 root canal.
      The purpose of this study was to investigate the prevalence of additional root
      canals in central and lateral mandibular incisors and to investigate the
      prevalence of oval and long oval canals in the cervical, middle, and apical
      thirds of cases with 1 root canal. METHODS: A total of 1016 Israeli patients'
      cone-beam computed tomography scans were screened and evaluated. A total of 1472
      central mandibular incisors and 1508 lateral mandibular incisors were examined.
      The root canal morphology and cross-sectional shape were recorded and analyzed.
      RESULTS: The overall prevalence of more than 1 root canal in mandibular central
      and mandibular lateral respectively was 40.5% and 37.9%. The bilateral incidence
      of more than 1 root canal in mandibular central and mandibular lateral
      respectively was 69.8% and 68.7%. The root canal separation in type II to type V
      central and lateral mandibular incisors was found in the middle third of the root
      in 81.5% and 79.0%, respectively. The septum was smaller than 1 mm in 37% of
      central mandibular incisors and one-third of lateral mandibular incisors. In
      central and lateral incisors with 1 root canal, long oval canals were found in
      the middle third of the root of central and lateral mandibular incisors in 36.8%
      and 48.9%, respectively. CONCLUSION: The occurrence of more than 1 root canal in
      central and lateral mandibular incisors is approximately 40% (type III was the
      predominant canal type). In central and lateral incisors with 1 root canal, long
      oval canals are common.

PMID- 29033083
TI  - Foraminal Deformation after Foraminal Enlargement with Rotary and Reciprocating
      Kinematics: A Scanning Electronic Microscopy Study.
AB  - INTRODUCTION: The aim of this study was to evaluate, under scanning electronic
      microscopy, the morphological aspect of apical foramen after root canal
      instrumentation with rotary and reciprocating kinematics at 2 different working
      length determinations. METHODOLOGY: Sixty mesiobuccal roots of mandibular and
      maxillary molars presenting with curvature ranging from 30 to 65 degrees  were
      used in this study. The roots were initially scanned with a scanning electronic
      microscope under *50 magnification. Roots were divided into 2 different groups (n
      = 30): group 1 instrumented with rotary kinematics, and group 2 instrumented with
      reciprocating kinematics. Both groups were instrumented at 2 different working
      lengths: at the apex and 1 mm beyond the apex. The roots were scanned after the
      instrumentation at the apex and again after further instrumentation 1 mm beyond
      the apex. The photomicrographs obtained were assigned to 3 independent evaluators
      for foraminal deformation assessment through comparison with baseline images.
      Evaluators were masked with regard to the kinematics and working length used. The
      Pearson correlation test and Kruskal-Wallis test (method of Dunn) were used for
      statistical analysis (P < .05). RESULTS: The Pearson Correlation test showed good
      agreement among evaluators. Foraminal deformation was observed in instrumentation
      at the apex and 1 mm beyond the apex with both kinematics (P < .05). CONCLUSIONS:
      Within the limitations of this study, it can be concluded that root canal
      instrumentation at the apex or 1 mm beyond the apex promoted deformation of the
      major foramen, regardless of the kinematics.

PMID- 29033084
TI  - Morphological Characteristics and Classification of Mandibular First Molars
      Having 2 Distal Roots or Canals: 3-Dimensional Biometric Analysis Using Cone-beam
      Computed Tomography in a Korean Population.
AB  - INTRODUCTION: The aim of this study was to determine the morphologic
      characteristics of mandibular first molars having 2 canals in distal roots.
      Interorifice distance, buccal bone thickness, and root curvature were evaluated
      using cone-beam computed tomography images in a Korean population. METHODS: In
      total, 1958 mandibular first molars were evaluated in axial, coronal, sagittal,
      and paraxial planes. Distal roots having 2 canals were classified according to
      their root and canal shapes (2 roots, 2 canals [2R2C]; 1 root, 2 canals with 2
      apical foramina [1R2C(2-2)]; and 1 root, 2 canals with 1 apical foramen [1R2C(2
      1)]). The distances between orifices and the distance from the apex to the buccal
      bone plate were measured for each root canal shape (2R2C, 1R2C[2-2], and 1R2C[2
      1]). The curvature of distolingual (DL) roots was classified according to
      severity using 3-dimensional reconstructed images, and the direction of curvature
      was determined. The relationships of these characteristics to sex and side were
      evaluated. RESULTS: The prevalences of 2R2C, 1R2C(2-2), and 1R2C(2-1) were
      25.89%, 10.32%, and 14.15%, respectively. The distances between distobuccal (DB)
      and DL orifices were 3.77 +/- 0.74 mm for 2R2C, 3.02 +/- 0.65 mm for 1R2C(2-2),
      and 2.44 +/- 0.64 mm for 1R2C(2-1). The distances from the buccal plate to the DB
      canal were 3.84 +/- 1.35 mm for 2R2C, 5.33 +/- 1.41 mm for 1R2C(2-2), and 5.96 +/
      1.63 mm for 1R2C(2-1). The distance from the buccal plate to the DL canal was
      9.85 +/- 1.46 mm for 2R2C, and 8.28 +/- 1.50 mm for 1R2C(2-2). All distances
      differed significantly according to root canal configurations, and all were
      greater in men than women (P < .05), except for the DB-DL orifice distance in
      1R2C(2-2) and the DB to buccal cortical plate distance in all root configurations
      (P > .05). No significant difference between the left and right sides was found
      (P > .05). The prevalence of most severely curved DL roots (type III) was 62.92%,
      and the direction was commonly toward the buccal side (69.03%). CONCLUSIONS: The
      prevalence of mandibular first molars having 2 canals in distal roots was more
      than 50% in a Korean population. Interorifice distances between DB and DL canals
      and distances from the apex to the buccal cortical plate differed according to
      root and canal numbers and shapes.

PMID- 29033085
TI  - Correlation between Endodontic Infection and Periodontal Disease and Their
      Association with Chronic Sinusitis: A Clinical-tomographic Study.
AB  - INTRODUCTION: The proximity of the roots of maxillary posterior teeth to the
      maxillary sinus floor can be associated with the development of chronic maxillary
      sinusitis (CMS). Therefore, this study evaluated the correlation between the
      presence of endodontic infection and periodontal disease in maxillary posterior
      teeth and the presence of CMS. METHODS: A total of 83 patients (159 maxillary
      sinuses) were selected and underwent clinical dental examination to assess tooth
      mobility and pulp condition. In addition, cone-beam computed tomography was
      performed to evaluate the presence of periapical lesion and periodontal bone
      loss, and measure the distance from the root apex to the cortical of the
      maxillary sinus. The maxillary sinuses were divided into 2 groups: CMS and no
      maxillary sinusitis. Data were analyzed using chi2 test and binary logistic
      regression analysis (P < .05). RESULTS: Periodontal disease was positively
      associated with CMS, leading to a 3.45-fold higher association between these
      disorders (P < .05). CMS was significantly more common in patients with
      periodontal disease or endodontic infection in close proximity with the maxillary
      sinus. Periodontal disease or endodontic infection that was more distant from the
      maxillary sinus was more common in patients with no maxillary sinusitis (P <
      .05). To the extent that the tooth is more distant from the maxillary sinus
      floor, the chance of presenting CMS is reduced up to 2.5-fold (P < .05).
      CONCLUSION: Periodontal disease and proximity to the maxillary sinus are more
      common in cases of CMS, requiring a dental assessment and cone-beam computed
      tomography evaluation in patients with CMS with ineffective treatment.

PMID- 29033086
TI  - Intentional Replantation Techniques: A Critical Review.
AB  - INTRODUCTION: Techniques and armamentarium for intentional replantation have
      varied throughout the years with no universally accepted clinical treatment
      guidelines. A wide range of success rates has been reported, and accordingly,
      this treatment method has often been regarded as a treatment of last resort.
      However, recent studies have shown more consistent success rates as high as 88%
      to 95%. In light of these new studies, intentional replantation may now be
      considered a more commonly accepted treatment modality. The purpose of this
      review was to critically examine reported techniques for intentional
      replantation. METHODS: A search of the literature on intentional replantation
      techniques was performed using electronic databases including PubMed, Medline,
      and Scopus. A total of 3183 articles were generated and screened for relevance
      based on defined inclusion and exclusion criteria. Subsequently, 27 studies were
      included for critical review of technique. RESULTS: There has been an evolution
      in technique for intentional replantation over the decades. CONCLUSIONS: Numerous
      aspects of the procedure exhibit variations, whereas other aspects exhibit
      considerable consistency. Few studies reported techniques consistent with modern
      endodontic surgical principles.

PMID- 29033087
TI  - Micro-computed Tomography versus the Cross-sectioning Method to Evaluate Dentin
      Defects Induced by Different Mechanized Instrumentation Techniques.
AB  - INTRODUCTION: The objective of this study was to compare the methods of micro
      computed tomography (micro-CT) and cross-sectioning followed by stereomicroscopy
      in assessing dentinal defects after instrumentation with different mechanized
      systems. METHODS: Forty mesial roots of mandibular molars were scanned and
      divided into 4 groups (n = 10): Group R, Reciproc; Group PTN, ProTaper Next;
      Group WOG, WaveOne Gold; Group PDL, ProDesign Logic. After instrumentation, the
      roots were once again submitted to a micro-CT scan, and then sectioned at 3, 6,
      and 9 mm from the apex, and assessed for the presence of complete and incomplete
      dentinal defects under a stereomicroscope. The nonparametric Kruskal-Wallis,
      Friedman, and Wilcoxon tests were used in the statistical analysis. The study
      used a significance level of 5%. RESULTS: The total number of defects observed by
      cross-sectioning followed by stereomicroscopy was significantly higher than that
      observed by micro-CT, in all of the experimental groups (P <= .05). All of the
      defects identified in the postoperative period were already present in the
      corresponding preoperative period. There was no significant difference among the
      instrumentation systems as to the median numbers of defects, for either cross
      sectioning followed by stereomicroscopy or micro-CT, at all the root levels (P >
      .05). In the micro-CT analysis, no significant difference was found between the
      median numbers of pre- and postinstrumentation defects, regardless of the
      instrumentation system (P > .05). CONCLUSION: None of the evaluated
      instrumentation systems led to the formation of new dentin defects. All of the
      defects identified in the stereomicroscopic analysis were already present before
      instrumentation, or were absent at both time points in the micro-CT analysis,
      indicating that the formation of new defects resulted from the sectioning
      procedure performed before stereomicroscopy and not from instrumentation.

PMID- 29033088
TI  - Evaluation of Effect of Foraminal Enlargement of Necrotic Teeth on Postoperative
      Symptoms: A Systematic Review and Meta-analysis.
AB  - INTRODUCTION: The intentional enlargement of the apical foramen is designed to
      reduce the microbial load in the apical foramen, or even beyond, to levels more
      favorable for repair. This study provides a systematic review and meta-analysis
      to address the PICOS question: in adult patients who undergo endodontic
      treatment, does foraminal enlargement (FE) cause different postoperative symptoms
      in comparison with conventional endodontic treatment? METHODS: The PROSPERO
      registration number is CRD42017059921 and was conducted following the PRISMA
      statements. A broad search was conducted in the electronic databases PubMed, Web
      of Science, Scopus, Cochrane Library, and grey literature for articles published
      through May 2017. The MeSH terms "Pain," "Hyperemia," "Edema," "Hyperesthesia,"
      "Fistula," "Root canal preparation," "Tooth apex," "Periapical periodontitis,"
      "Dental pulp necrosis," and "Clinical study" were used. The reviewers evaluated
      the studies for eligibility criteria and performed data abstraction and risk of
      bias evaluations. A random-effects model was used for the meta-analysis. RESULTS:
      Five studies qualified for systematic review, and 3 studies were considered for
      meta-analysis. The results of the meta-analysis showed that postoperative pain is
      higher in the endodontic treatment with FE, with a statistically significant
      difference in the first, second, fourth, sixth, and seventh days. Limited data
      indicated that no significant difference was found in analgesic consumption,
      flare-up, and swelling between the groups. CONCLUSIONS: Postoperative pain was
      higher in the FE group compared with conventional endodontic therapy in the first
      days after treatment in teeth with necrosis and apical periodontitis.

PMID- 29033089
TI  - The Effect of Heating Time and Temperature on Epoxy Resin and Calcium Silicate
      based Endodontic Sealers.
AB  - INTRODUCTION: With the growing use of warm obturation techniques during
      endodontic treatment, more interest is directed toward sealers' compatibility
      with heat. This study aimed to evaluate the effect of heat application duration
      and temperature on epoxy resin- and calcium silicate-based sealers using chemical
      and thermogravimetric analyses. METHODS: Freshly mixed samples (n = 5/group) of
      each sealer were heated at 200 degrees C or 250 degrees C for 30 or 60 seconds.
      Additional 2 sets of samples were examined directly after mixing or after setting
      without heat exposure. Raman spectroscopy was used to identify changes in the
      chemical structure, and a 2-way analysis of variance was performed to compare
      values of measurable peaks that exhibited changes. Additionally,
      Thermogravimetric Analysis (TGA) was used to evaluate the effect of heat on mass
      change where sealers were heated to 250 degrees C at a rate of 20 degrees C/min
      (11-minute duration) or maintained at 37 degrees C for 8 hours. RESULTS: No
      differences were detected among all the spectra of calcium silicate samples of
      different groups, while TGA revealed 15% and 18% weight loss upon heating at 250
      degrees C and 37 degrees C, respectively. For the resin sealer, significant
      differences were detected when samples were heated for 60 seconds, involving
      bonds of benzene rings and aromatic amines in the uncured resin. TGA revealed
      minimal changes in the sealer mass (1.2% and 1.8%) on heating at 250 degrees C
      and 37 degrees C, respectively. CONCLUSIONS: Heat application duration and
      temperature can affect the chemical structure of epoxy resin sealers. The
      consideration of endodontic sealer compatibility as well as the duration of heat
      application is essential when warm vertical obturation is used.

PMID- 29033090
TI  - The Antimicrobial Peptide LL-37 as a Possible Adjunct for the Proliferation and
      Differentiation of Dental Pulp Stem Cells.
AB  - INTRODUCTION: This study evaluated the biocompatibility of 5 and 10 MUg/mL LL-37
      in vitro and its effect on the differentiation of human dental pulp stem cells
      (DPSCs) into odontoblast-like cells. METHODS: Cell viability, genotoxicity,
      nitric oxide production, cell cycle, dentine sialophosphoprotein (DSPP)
      production, and DSPP gene expression. RESULTS: Concentrations of 5 and 10 MUg/mL
      of LL-37 were not cytotoxic and generally increased cell viability, especially on
      the third day (P < .05). The tested concentrations did not induce genotoxicity (P
      < .05). LL-37 did not significantly alter nitrite production at either
      concentration. Cell cycle analysis revealed that 10 MUg/mL of LL-37 arrested
      cells in G0/G1 (P < .05). The control group exhibited higher numbers of cells in
      other phases of the cell cycle (P < .05). The expression of the DSPP protein and
      gene was also higher in the 10 MUg/mL of LL-37 group (P < .05). CONCLUSIONS:
      These results demonstrated that LL-37 was biocompatible at these concentrations
      and increased the number of viable cells, especially during the initial period.
      The 10 MUg/mL concentration arrested the cell cycle and increased expression of
      the DSPP protein and gene, which indicates that this peptide contributes to
      odontoblastic differentiation.

PMID- 29033091
TI  - Influence of Artifact Reduction Tools in Micro-computed Tomography Images for
      Endodontic Research.
AB  - INTRODUCTION: Micro-computed tomography (MUCT) is an imaging modality of growing
      application in endodontic research because of its nondestructive technology that
      enables visualization at the micrometer level. In the presence of high-density
      material, images acquired with MUCT may present artifacts. Thus, the aim of this
      study was to evaluate subjectively and objectively the influence of artifact
      reduction tools available for MUCT image reconstruction to determine whether
      their use can influence endodontic research outcomes. METHODS: Ten teeth were
      scanned in a MUCT device, and these images were reconstructed by applying 13
      protocols of artifact reduction tools, combining ring artifact reduction (RAR)
      and beam-hardening artifact reduction (BAR). Images were assessed subjectively
      (observer's preference) and objectively (root canal surface area and volume).
      Observer's preference for RAR and BAR protocols was tested by chi2. Analysis of
      variance was used to compare volumes and surface area of root canals on different
      protocols. Intraobserver and interobserver reproducibility was calculated by the
      weighted kappa test. RESULTS: There was no preference for a particular protocol
      for BAR (P = .91) or RAR (P = .80). There were no statistically significant
      differences for volume (P = .999) or surface area (P = .972) of root canals for
      all protocols. CONCLUSIONS: To evaluate root canal volume and root canal surface
      area, artifact reduction tools applied to MUCT images can be used according to
      the observer's visual preference without influence on objective image analysis.

PMID- 29033092
TI  - Comparison of IL-1beta, TNF-alpha, hBD-2, and hBD-3 Expression in the Dental Pulp
      of Smokers Versus Nonsmokers.
AB  - INTRODUCTION: To date, the endodontic literature lacks research on the effect of
      smoking on cytokine and defensin expression in the dental pulp. Therefore, the
      aim of this study was to investigate the expression of interleukin (IL)-1beta,
      tumor necrosis factor (TNF)-alpha, human beta defensin (hBD)-2 and hBD-3 in the
      dental pulp of smokers and compare them with nonsmokers. We hypothesized that
      cytokine and defensin expression would be reduced in smokers as compared with
      nonsmokers. METHODS: Thirty-two smokers and 37 nonsmokers with endodontic pulpal
      diagnoses of normal, symptomatic irreversible pulpitis and asymptomatic
      irreversible pulpitis were included in this cross-sectional study. Samples from
      pulp chambers were collected and stored in phosphate-buffered saline at -80
      degrees C. Luminex was used to measure IL-1beta and TNF-alpha levels. The levels
      of hBD-2 and hBD-3 were measured using enzyme-linked immunosorbent assay. Marker
      levels were normalized to protein concentrations and data were analyzed using
      Kruskal-Wallis test, Mann-Whitney U test, and 2-way analysis of variance (alpha =
      0.05). RESULTS: Pulpal concentrations of TNF-alpha and hBD-2 were significantly
      lower among smokers (P < .01), whereas no significant difference was observed for
      IL-1beta, or hBD-3. Two-way analysis of covariance revealed that smoking status
      (P < .001), not endodontic diagnosis (pulpal status), significantly affected TNF
      alpha and hBD-2 levels. CONCLUSIONS: This study reported that smokers are
      immunologically deficient in TNF-alpha and hBD-2, suggesting that dental pulps of
      smokers possess limited defense mechanisms, affecting their endodontic prognosis
      and indicating a cause for their reported inferior outcome.

PMID- 29033093
TI  - Meeting Our Patients "Where They Are": Video-Group Smoking Cessation for People
      Living With HIV.

PMID- 29033094
TI  - Necessity of Axillary Scanning After Negative Finding on Both Mammography and
      Subsequent Breast Ultrasound.
AB  - The purpose of our study was to assess the cancer detection rate and positive
      predictive value (PPV) for incidentally detected abnormal axillary lymph nodes
      with negative mammography and subsequent breast ultrasound (US). We included 7039
      screened patients (mean age, 52 y) from January 2012 to March 2015 with negative
      mammography and subsequent breast US results. In two patients with positive lymph
      nodes, neither were from breast malignancy. The calculated cancer detection rate,
      PPV for biopsy and axillary biopsy rate was 0.3 per 1000 axillary US, 14.3% and
      0.2%. Cancer rates for patients with a family or personal operation history, with
      cancer history and with no family/operation/cancer history were 0%, 0.1% and
      0.2%, respectively. Our results indicate that the cancer detection rate and PPV
      for US were too low to recommend routine axillary scanning including screening
      breast US in patients with negative mammography and subsequent breast US,
      especially with no history of any cancers.

PMID- 29033095
TI  - Automatic Measurements of Mitral Annular Plane Systolic Excursion and Velocities
      to Detect Left Ventricular Dysfunction.
AB  - The purpose of the study described here was to evaluate an automatic algorithm
      for detection of left ventricular dysfunction, based on measurements of mitral
      annular motion indices from color tissue Doppler apical four-chamber recordings.
      Two hundred twenty-one patients, among whom 49 had systolic and 11 had diastolic
      dysfunction, were included. Echocardiographic evaluation by cardiologists was the
      reference. Twenty patients were also examined by medical students. The ability of
      the indices to detect systolic and diastolic dysfunction were compared in
      receiver operating characteristic analyses, and the agreement between automatic
      and reference measurements was evaluated. Mitral annular plane systolic excursion
      <=10 mm detected left ventricular dysfunction with 82% specificity, 76%
      specificity, 56% positive predictive value and 92% negative predictive value. The
      automatic measurements acquired from expert recordings better agreed better with
      the reference than those acquired from student recordings. We conclude that
      automatic measurements of systolic mitral annular motion indices can be helpful
      in detection of left ventricular dysfunction.

PMID- 29033096
TI  - Re: Left Ventricular Strain and Rotation by 2-D Speckle Tracking Echocardiography
      Identify Early Alcoholic Cardiomyopathy.

PMID- 29033098
TI  - Moving toward a precision medicine approach in metastatic castration-resistant
      prostate cancer.

PMID- 29033097
TI  - A systematic review of the inclusion of mechanisms of action in NIH-funded
      intervention trials to improve medication adherence.
AB  - Medication nonadherence contributes to morbidity/mortality, but adherence
      interventions yield small and inconsistent effects. Understanding the mechanisms
      underlying initiation and maintenance of adherence could improve interventions.
      The National Institutes of Health (NIH) support adherence research, but it is
      unclear whether existing NIH-funded research incorporates mechanisms. We
      conducted a systematic review to determine the proportion of NIH-funded adherence
      trials that have tested hypothesized mechanisms of intervention effects. We
      included randomized and quasi-randomized NIH-funded trials with medication
      adherence in adults as the primary outcome. Studies were identified by searching
      electronic databases from inception to 6/2016, references, and
      clinicaltrials.gov. Two of 18 (11%) NIH-funded trials tested a hypothesized
      mechanism of an intervention's effect on medication adherence. Another 44 studies
      with medication adherence as a secondary outcome were described in protocol form,
      and are either ongoing or never published results, but none mentioned mechanism
      tests. Overall, 3% of NIH-funded trials with adherence as an outcome conducted,
      or plan to conduct, tests of behavior change mechanisms. These results mirror
      previous findings that very few studies of behavior change interventions actually
      test the mechanism by which the intervention is hypothesized to improve health
      behaviors. We must understand mechanisms if we are to improve the effectiveness
      of interventions.

PMID- 29033100
TI  - Oxytocin receptors (OXTR) and early parental care: An interaction that modulates
      psychiatric disorders.
AB  - Oxytocin plays an important role in the modulation of social behavior in both
      typical and atypical contexts. Also, the quality of early parental care sets the
      foundation for long-term psychosocial development. Here, we review studies that
      investigated how oxytocin receptor (OXTR) interacts with early parental care
      experiences to influence the development of psychiatric disorders. Using Pubmed,
      Scopus and PsycInfo databases, we utilized the keyword "OXTR" before subsequently
      searching for specific OXTR single nucleotide polymorphisms (SNPs), generating a
      list of 598 studies in total. The papers were catalogued in a database and
      filtered for gene-environment interaction, psychiatric disorders and involvement
      of parental care. In particular, rs53576 and rs2254298 were found to be
      significantly involved in gene-environment interactions that modulated risk for
      psychopathology and the following psychiatric disorders: disruptive behavior,
      depression, anxiety, eating disorder and borderline personality disorder. These
      results illustrate the importance of OXTR in mediating the impact of parental
      care on the emergence of psychopathology.

PMID- 29033099
TI  - Custirsen (OGX-011) combined with cabazitaxel and prednisone versus cabazitaxel
      and prednisone alone in patients with metastatic castration-resistant prostate
      cancer previously treated with docetaxel (AFFINITY): a randomised, open-label,
      international, phase 3 trial.
AB  - BACKGROUND: Docetaxel and cabazitaxel improve overall survival compared with
      mitoxantrone in patients with metastatic castration-resistant prostate cancer.
      Custirsen (OGX011) is a second generation highly specific antisense
      oligonucleotide that inhibits the production of clusterin, an antiapoptotic
      protein that is upregulated in response to chemotherapy and that confers
      treatment resistance. We aimed to assess whether custirsen in combination with
      cabazitaxel and prednisone increases overall survival in patients with metastatic
      castration-resistant prostate cancer previously treated with docetaxel. METHODS:
      In this randomised, open-label, international, phase 3 trial, men with
      radiographically documented metastatic castration-resistant prostate cancer that
      had progressed after docetaxel treatment with a Karnofsky performance status of
      more than 70% and who were fit for chemotherapy, were recruited from 95 cancer
      treatment centres in eight countries. Patients were randomly assigned (1:1)
      centrally using permuted blocks (block size 8) to receive cabazitaxel plus
      prednisone (cabazitaxel 25 mg/m2 intravenously every 21 days plus oral prednisone
      10 mg daily) with or without custirsen (640 mg intravenously on days 1, 8, and
      15, plus three previous loading doses) until disease progression, unacceptable
      toxicity, or the completion of ten treatment cycles. Randomisation was stratified
      by use of opioids for prostate cancer-related pain at screening, disease
      progression following first-line docetaxel treatment established by radiographic
      evidence, and previous treatment with abiraterone or enzalutamide. The co-primary
      endpoints were overall survival in all randomly assigned patients and in a poor
      prognosis subgroup. All analyses were intention to treat with the exception of
      safety, which was reported for patients who received any assigned treatment. The
      trial has been completed and the results presented here are the final analysis.
      This trial is registered with Clinicaltrials.gov, number NCT01578655. FINDINGS:
      Between Sept 9, 2012, and Sept 29, 2014, 795 patients were screened for
      enrolment. 635 men were eligible for inclusion and were randomly assigned (n=317
      in the cabazitaxel and prednisone plus custirsen group and n=318 in the
      cabazitaxel and prednisone group). Median follow up was 28.3 months (IQR 24.4
      34.5) for the custirsen group and 29.8 months (IQR 25.3-35.2) for the control
      group. Median overall survival in all randomly assigned patients did not differ
      between the two groups (14.1 months [95% CI 12.7-15.9] in the curtisen group vs
      13.4 months [12.1-14.9] in the control group; hazard ratio [HR] 0.95 [95% CI 0.80
      1.12]; log-rank p=0.53). In the poor prognosis subgroup, median overall survival
      also did not differ between the two treatment groups (11.0 months [95% CI 9.3
      13.3] in the custursin group vs 10.9 months [8.2-12.4] in the control group; HR
      0.97 [95% CI 0.80-1.21]; two-sided p=0.80). The most frequently reported grade 3
      or worse adverse events in the custirsen versus control groups were neutropenia
      (70 [22%] of 315 vs 61 [20%] of 312), anaemia (68 [22%] vs 49 [16%]), fatigue (23
      [7%] vs 18 [6%]), asthenia (16 [5%] vs 8 [3%]), bone pain (16 [5%] vs 5 [2%]),
      and febrile neutropenia (16 [5%] vs 9 [3%]). Serious adverse events were reported
      in 155 (49%) versus 132 (42%). 27 patients died within 30 days of treatment in
      the cabazitaxel and prednisone plus custirsen group, seven of which were deemed
      to be treatment related, versus 17 in the cabazitaxel and prednisone group, eight
      of which were deemed to be treatment related. Of the 21 deaths reported, 15 were
      reported as complications related to study treatment, either chemotherapy (eight
      and three, respectively) or study drug (none and four, respectively).
      INTERPRETATION: We noted no survival benefit in men with metastatic castration
      resistant prostate cancer with the addition of custirsen to cabazitaxel and
      prednisone treatment. Cabazitaxel and prednisone remains the standard of care for
      patients with metastatic castration-resistant prostate cancer progressing after
      docetaxel chemotherapy. FUNDING: OncoGenex Pharmaceuticals.

PMID- 29033101
TI  - Re: Salvage High-intensity Focused Ultrasound (HIFU) for Locally Recurrent
      Prostate Cancer After Failed Radiation Therapy: Multi-institutional Analysis of
      418 Patients.

PMID- 29033102
TI  - [18F]-Fluorodeoxyglucose Positron Emission Tomography and Response to Therapy in
      Idiopathic Retroperitoneal Fibrosis.

PMID- 29033103
TI  - Re: Metastasis-free Survival Is a Strong Surrogate of Overall Survival in
      Localized Prostate Cancer.

PMID- 29033104
TI  - Progesterone-releasing devices for cattle estrus induction and synchronization:
      Device optimization to anticipate shorter treatment durations and new device
      developments.
AB  - Synchronization programs using progesterone-releasing intravaginal devices that
      allow for fixed time artificial insemination are still finding increasing
      application in bovine reproduction. This practice is useful for rationalizing
      livestock management because an increased number of cows can be inseminated in
      one session without the need for estrus detection. Although much of the
      innovation related to the design and development of intravaginal devices for use
      in cattle took place in the previous century, progress in understanding the
      physiology of the bovine estrous cycle resulted in shorter treatment durations, a
      trend which is still continuing. In this competitive market, with little
      functional differentiation between the existing devices, the shorter treatment
      duration prompted for optimization of the progesterone content in the device, as
      the cost of the drug significantly contributes to the price per unit. For CIDR(r)
      a reduction of the progesterone content of about 30 per cent was realized. Price
      reduction remained an important target for further device development. Next to
      reduction of progesterone content, cheaper and easier to process materials like
      polyethylene vinyl acetate (EVA) copolymers have been explored to replace the
      commonly used silicone elastomers. The reengineering effort of CIDR(r)
      demonstrated that knowledge of release kinetics and insight into gradual
      depletion patterns in the device is critical for optimization of drug content
      without compromising performance (blood levels). More recent publications related
      to the use of alternative polymers like EVA and polyisoprene (IP) indicated
      encouraging results regarding further reduction of progesterone content. The use
      of EVA seems most promising, because it is in principle a low-cost polymer
      available in many grades and this thermoplastic polymer can be processed easily
      by means of commonly used techniques like injection molding and extrusion. The
      use of thermoplastic polymers, however, requires insight into the physical
      chemical phenomena related to drug dissolution and re-crystallization taking
      place in the polymer during processing at high temperatures. These aspects, which
      may critically affect product stability, are often overlooked and are prompting
      to cover some of the background in this review. Finally, two different innovative
      approaches are discussed, one related to programable electronic devices for
      tailored simultaneous drug release and the other is a flexible drug-loaded helix,
      which is retained very well in several species without causing the usual
      inflammatory response.

PMID- 29033105
TI  - Public Attitudes Toward Expanded Newborn Screening.
AB  - PURPOSE: There is limited research available on public knowledge and
      understanding of expanded newborn screening (NBS). The aims of this study were to
      assess current public knowledge and understanding of newborn screening disorders
      and procedures, perceived education needs, and preferences for the delivery of
      NBS information and education. An additional aim was to develop a beginning
      understanding of public attitudes toward screening for complex, severe, and in
      some cases untreatable disorders. DESIGN AND METHODS: In this preliminary
      descriptive study, eighty-eight participants completed surveys querying their
      general knowledge of NBS, preferred means of receiving NBS information and
      education, and their opinions about screening for severe disorders such as
      lysosomal storage diseases (LSD). RESULTS: Most study participants lacked general
      knowledge about current NBS practices, however, they supported expanding
      screening for severe and in some cases untreatable conditions. Most participants
      were enthusiastic about expanding NBS; however, those with more years of
      education were cautious regarding extensive costs of diagnosing and treating rare
      disorders. CONCLUSIONS: Newborn screening continues to evolve through new
      technological developments and the addition of more disorders to screening
      panels. More research of into public acceptance of newborn screening is needed.
      Addressing the educational needs of the public is important for improving their
      understanding of NBS and promoting patient-centered care in the era of genomic
      screening. PRACTICE CONSIDERATIONS: Enhanced educational efforts are necessary
      for improving public understanding of newborn screening.

PMID- 29033106
TI  - Current options for mechanical prevention of preterm birth.
AB  - Cervical insufficiency can be defined by a combination of obstetric history,
      cervical dilation on exam, and/or short cervical length in women with prior
      preterm birth. Options for mechanical intervention include cerclage and pessary.
      There is evidence to support the benefit of a cervical cerclage in women with
      singleton gestations who have a diagnosis of cervical insufficiency either based
      on second trimester painless cervical dilatation leading to recurrent early
      preterm births, or a history of early spontaneous preterm birth and a second
      trimester transvaginal ultrasound short cervical length or cervical dilation on
      exam. For women with multiple gestations, the benefit of a cerclage is uncertain,
      and further study is warranted. The pessary has also been studied for mechanical
      prevention of preterm birth in various populations, however the results so far
      have been mixed and warrants further study prior to routine use.

PMID- 29033107
TI  - Soluble urokinase-type plasminogen activator receptor (suPAR) and interleukin-6
      levels in hyperemesis gravidarum.
AB  - BACKGROUND: The aim was to compare serum soluble urokinase-type plasminogen
      activator receptor (suPAR) levels as well as interleukin-6 levels (IL-6) in
      pregnant women with hyperemesis gravidarum (HG) and asymptomatic pregnant women.
      METHODS: Our study population consists of voluntary first trimester-pregnant
      women who applied to the outpatient clinic of the department of obstetrics and
      gynecology of Ankara Ataturk Training and Research Hospital. Between February and
      May 2016, 60 pregnant women were included in our prospective study. Serum suPAR
      and IL-6 levels were evaluated with the ELISA method. Twenty-nine pregnant women
      with HG and 31 asymptomatic pregnant women were included in the study. RESULTS:
      Serum suPAR level in the HG group was measured as 0.36 +/- 0.56 ng/ml, whereas
      this level in the healthy pregnant control group was measured as 0.15 +/- 0.15
      ng/ml (p < 0.05). The interleukin-6 level in the HG group was 5.69 +/- 2.16
      pg/ml, whereas in the control group it was measured as 3.88 +/- 0.28 pg/ml (p <
      0.05). CONCLUSION: Serum suPAR and IL-6 levels proved to be high in the HG group.
      It is likely that suPAR could play a role in the etiopathogenesis of hyperemesis
      gravidarum.

PMID- 29033108
TI  - Clinical course in infants diagnosed with transient tachypnea of newborn: A
      clinical trial assessing the role of conservative versus conventional management.
AB  - BACKGROUND: Transient tachypnea of the newborn (TTN) is a respiratory disorder
      secondary to inadequate or delayed clearance of lung fluids. Early symptoms of
      the disease are indistinguishable from neonatal respiratory distress syndrome,
      pneumonia, and persistent pulmonary hypertension. Therefore, these newborns, in
      addition to receiving conservative management, receive antibiotics until blood
      cultures provide definite results. In this study, we assessed the clinical course
      of neonates diagnosed with TTN who received conventional versus conservative
      management. METHODS: One hundred and thirty neonates diagnosed as having TTN were
      randomly enrolled in two study groups. While patients belonging to one group
      received conservative management, those from the other group were treated with
      conventional medical therapy. RESULTS: Mean duration of hospitalization was 7 +/-
      0.2 in the conventional and 5 +/- 1.5 in the conservative group. Duration of
      antibiotic therapy was 6.7 +/- 2.47 days in the conventional group. CONCLUSION:
      Newborns diagnosed with TTN without prenatal risk factors and a negative C
      reactive protein test do not need to be administered antibiotics and hospitalized
      until confirmatory blood culture results are obtained.

PMID- 29033109
TI  - Three years of the nationwide post-acute stroke care program in Taiwan.
AB  - Prolonged hospital stay and readmission are prevalent problems for stroke
      patients in Taiwan after the acute stage, partly due to the unmet need of post
      acute care. In March 2014, Taiwan's National Health Insurance Administration
      launched a nationwide Post-Acute Care-CerebroVascular Disease (PAC-CVD) program.
      The Taiwan Stroke Society, coordinating 11 allied disciplines, took
      responsibility for the preparation and implementation of the program. As of June
      2016, 6839 consecutive stroke patients were enrolled. On discharge from the PAC
      program, the functional status had improved in 87.5% of patients, with a
      significant decrease in the mean modified Rankin Scale score from 3.7 to 3.0. The
      rates of readmission and mortality in the PAC group were also lower than in the
      control group. In conclusion, the Taiwan's PAC-CVD program is an innovative and
      essentially effective national program of post-acute stroke care. We believe such
      experience should be helpful for policy makers of stroke care worldwide.

PMID- 29033110
TI  - Investigating of four main carbapenem-resistance mechanisms in high-level
      carbapenem resistant Pseudomonas aeruginosa isolated from burn patients.
AB  - BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen involved in many
      infections. Carbapenem-resistant P.aeruginosa has emerged as an important cause
      of infection in different hospitals worldwide. We aimed to determine frequencies
      of the four main resistance mechanisms [metallo-beta lactamase (MBL) production
      (blaIMP, blaVIM, blaSPM and blaNDM), overproduction of the MexAB-OprM and MexXY
      efflux pumps, overproduction of chromosome-encoded AmpC beta-lactamase, and
      reduced OprD expression] in high-level carbapenem-resistant P.aeruginosa isolated
      from patients with burns. METHODS: In a descriptive study, 107 P. aeruginosa
      isolates were collected from patients with burn injuries and tested for
      antibiotic susceptibility, by an E-test for carbapenems, an E-test for metallo
      beta-lactamase producer isolates, and PCR to detect MBL genes. Furthermore, high
      level carbapenem-resistant isolates were tested by real-time PCR for the
      expression levels of the mexB, mexY, ampC, and oprD genes. RESULTS: Amongst all
      P. aeruginosa isolates, 78.5%, 46.7%, and 15% were imipenem-, meropenem-, and
      doripenem-resistant, respectively; 72% of isolates were multidrug-resistant. The
      blaIMP and blaVIM genes were detected in 17.9% and 1.2% of isolates;
      respectively. The blaSPM and blaNDM genes were not observed. Among the resistant
      isolates, mexB overexpression (63.2%) was the most frequent mechanism, followed
      by mexY overexpression (52.6%), ampC overexpression (36.8%), and reduced oprD
      expression (21.1%). CONCLUSION: Emerging antimicrobial resistance in burn wound
      bacterial pathogens is a serious therapeutic challenge for clinicians. In the
      present study, most of the isolates were MDR. This finding indicated an alarming
      spread of resistant isolates and suggested that infection control strategies
      should be considered. Resistance to carbapenems is influenced by several factors,
      not all of which were evaluated in our study; however, the results showed that
      production of MBLs and overexpression of the mexB gene were the most frequent
      mechanisms in carbapenem-resistant isolates.

PMID- 29033111
TI  - Screening tools for neuropathic pain.

PMID- 29033113
TI  - A new facilitating technique for postpartum hysterectomy at full dilatation:
      Cervical clamp.
AB  - BACKGROUND: Postpartum hysterectomy is a life saving emergency procedure in the
      management of uncontrollable severe maternal hemorrhage that every obstetrician
      should be closely acquainted with despite developments in medical and non
      surgical interventions for obstetric hemorrhage. It can be difficult to detect
      the real boundaries of the cervix at full effacement and dilatation in patients
      who undergo emergency hysterectomy after vaginal delivery. METHODS: Hereby we
      propose a simple and effective method to ease the operation by placing two
      atraumatic ring forceps to the anterior and posterior sides of the cervix during
      the preoperative vaginal examination and leave the two ring forceps while taking
      the patient into surgery. The boundary of the vagina and cervix will be
      determined with the help of the ring forceps intraoperatively, which are already
      placed before the operation. RESULTS: Cervical clamp technique was successfully
      performed in four cases underwent to emergency postpartum hysterectomy due to
      uncontrollable postpartum atony. There were no postoperative complication and re
      exploration for the persistent hemorrhage. Postoperative FSFI scores of the cases
      were 26.7, 27.4, 30.3 and 30.7. CONCLUSION: Taking extra vaginal tissue from the
      lower level of the cervix may be avoided and the last stage of the total
      hysterectomy may be facilitated by this simple technique with ensuring of
      bleeding management.

PMID- 29033112
TI  - Gap between guidelines and clinical practice in heart failure with reduced
      ejection fraction: Results from TSOC-HFrEF registry.
AB  - BACKGROUND: Heart failure (HF) is a global health problem. Guidelines for the
      management of HF have been established in Western countries and in Taiwan.
      However, data from the Taiwan Society of Cardiology-Heart Failure with reduced
      Ejection Fraction (TSOC-HFrEF) registry showed suboptimal prescription of
      guideline-recommended medications. We aimed to analyze the reason of non
      prescription and clinical outcomes as a result of under-prescription of
      medications. METHODS: A total of 1509 patients hospitalized for acute HFrEF were
      recruited in 21 hospitals in Taiwan by the end of October 2014. Prescribed
      guideline-recommended medications and other relevant clinical parameters were
      collected and analyzed at discharge and 1 year after index hospitalization.
      RESULTS: At discharge, 62% of patients were prescribed with either angiotensin
      converting enzyme-inhibitors (ACEI) or angiotensin receptor blockers (ARB); 60%
      were prescribed with beta-blockers and 49% were prescribed with mineralocorticoid
      receptor antagonists (MRA). The proportions of patients at >=50% of the target
      dose for ACEI/ARB, beta-blockers and MRA were 24.4%, 20.6%, 86.2%, respectively.
      At 1-year follow-up, dosages of ACEI/ARB and MRA were up-titrated in about one
      fourth patients, and dosages of beta-blocker were up-titrated in about 40%
      patients. One-year mortality rate was lowest in patients who received at least 2
      classes of guideline-recommended medications with >=50% of the target dose, and
      highest in those who received 0 or 1 class of medications. CONCLUSION: The TSOC
      HFrEF registry demonstrated the under-prescription of guideline-recommended
      medications and reluctance of physicians to up-titrate medications to target
      dose. Action plan needs be formulated in order to improve physician's adherence
      to HF guidelines.

PMID- 29033114
TI  - A bibliometric and social network analysis of pelvic organ prolapse during 2007
      2016.
AB  - BACKGROUND: Pelvic organ prolapse (POP) seriously affects the life quality of old
      females. In the present work, we described the knowledge structure of POP in a
      macroscopic view, and summarized the recent research focus. METHODS: Candidates
      were identified through reading and screening publications from PubMed database
      with a MeSH term of "pelvic organ prolapse" during 2007-2016. Relevant journals
      and journal-affiliated countries were extracted, and essential information, such
      as the number of publication of each year, first authors and MeSH/subheading
      words, was analyzed with BICOMB. In addition, highly-frequent MeSH/subheading
      words were determined and classified, and co-occurrence matrices were produced
      accordingly. Finally, social network was utilized to analyze the knowledge
      structure. RESULTS: A total of 3294 publications of POP were retrieved from 364
      journals. The publication of POP had a significant downward trend since the
      beginning of 2015. POP articles published in American and British journals were
      significantly more compared with other countries. The co-occurrence matrices of
      37 * 37 and 55 * 55 were produced by the highly-frequent MeSH/subheading words,
      and then the social network analysis was performed based on them. CONCLUSION:
      These publications on POP were mainly from the developed countries. Surgical
      treatment of POP was a hot topic of POP research in recent 10 years.

PMID- 29033115
TI  - The impact of a quality improvement program on perioperative dental injuries.

PMID- 29033116
TI  - Delivering normative feedback to heavy drinking college students via text
      messaging: A pilot feasibility study.
AB  - Correcting misperceptions in drinking norms is an established method of reducing
      college student drinking; however, delivery of accurate norms has typically been
      limited to a single dose within the confines of an alcohol intervention. The
      present study tests the feasibility, acceptability, and preliminary efficacy of
      using text messages to promote pro-moderation descriptive and injunctive norms.
      Following a baseline survey, 68 heavy drinking college students were randomly
      assigned to receive 28 daily messages with either accurate norms information
      (experimental group, n=34) or fun facts (control group, n=34). Participants rated
      each message on a 5-point scale of interest, and at the end of the 28days
      completed a follow-up assessment of normative perceptions and drinking behavior.
      The study protocol was feasible: 87% of invited students completed the screener,
      64% of eligible students completed the consent form, and 93% agreed to
      participate. All messages were delivered and 98% were rated. Regarding
      acceptability, the mean interest rating for the alcohol-related text messages was
      2.84 (SD=1.30), and no participants withdrew from the study. Although between
      group differences were not observed at follow-up, participants in the
      experimental group showed significant reductions between baseline and follow-up
      on peak drinks, frequency of heavy episodic drinking (HED), negative
      consequences, and injunctive norms (ps<0.01). Results lay the groundwork for
      development of a text-based prevention strategy for use in college settings.

PMID- 29033117
TI  - PTGER2 activation induces PTGS-2 and growth factor gene expression in endometrial
      epithelial cells of cattle.
AB  - The prostaglandin E2 receptor 2 (PTGER2) is present in the endometrium and its
      gene expression is accompanied with endometrial growth, however, it is unknown
      whether there is endometrial repair through stimulation of growth factor gene
      expression that is promoted by PTGER2 activation in cattle. The aim of this study
      was to investigate whether PTGER2 activation can induce prostaglandin
      endoperoxide synthase-2 (PTGS-2) and growth factor gene expression by activating
      PKA and ERK signaling pathways in endometrial epithelial cells of cattle. Results
      demonstrated that the PTGER2 agonist, butaprost, induced cAMP/PKA and ERK
      activation and up-regulated PTGS-2, VEGF, CTGF, TGF-beta1 and IL-8 gene
      expression. These activations were less after PTGER2 antagonist, AH6809,
      treatment. Data suggested that PTGS-2 gene expression was induced by PTGER2
      activation through the PKA and ERK pathways. Furthermore, PTGER2 activation
      promoted several growth factor gene expressions in endometrial epithelial cells.
      One potential implication of this finding is that PTGER2 activation in the
      endometrium of cattle could induce endometrial repair by stimulating VEGF, CTGF,
      TGF-beta1 and IL-8 gene expression.

PMID- 29033118
TI  - Physical activity, stigma, and quality of life in patients with epilepsy.
AB  - Indication of physical activity (PA) for people with epilepsy (PWE) is debatable.
      This study investigated whether the International Physical Activity Questionnaire
      (IPAQ) score is related to the clinical aspects of epilepsy, QOLIE-31, and the
      Stigma Scale of Epilepsy (SSE) score of 67 PWE at a significance level of 5%
      (p<0.05). About one-third (32.8%) of the PWE were sedentary/irregularly active.
      Lower QOLIE-31 scores and higher SSE scores were found in PWE who did not
      practice PA for fear of seizures and in sedentary/irregularly active PWE. Twenty
      three percent of the PWE stopped practicing PA for fear of seizures. The
      predictive factors in the logistic regression equation for not practicing
      physical activity for fear of seizures were the presence of depressive disorder
      (p=0.049) and temporal lobe epilepsy with hippocampal sclerosis (TLE-HS)
      (p=0.024). Most PWE are sedentary and do not practice PA for fear of seizures.
      Physical activity is negatively influenced by clinical aspects of epilepsy. Less
      PA is associated with depressive disorder, worse quality of life, and higher
      perception of stigma.

PMID- 29033119
TI  - Interpregnancy weight change and adverse maternal outcomes: a retrospective
      cohort study.
AB  - PURPOSE: Examine associations between interpregnancy body mass index (BMI) change
      (difference in the pre-pregnancy BMIs of two consecutive pregnancies) and
      gestational diabetes mellitus (GDM), pre-eclampsia (PE), gestational hypertension
      (GHtn), primary cesarean delivery, and vaginal birth after cesarean delivery
      (VBAC). METHODS: Modified Poisson regression models estimated adjusted
      associations. RESULTS: Every 1-unit increase in interpregnancy BMI increased
      risks of GDM (relative risk [RR]: 1.09; 95% confidence interval [CI], 1.07-1.11),
      PE (RR: 1.06; 95% CI, 1.04-1.09), GHtn (RR: 1.08; 95% CI, 1.06-1.10), and primary
      cesarean delivery (RR: 1.03; 95% CI, 1.01-1.05) and decreased the risk of a
      successful VBAC (RR: 0.98; 95% CI: 0.97-0.997) in the second pregnancy. A BMI
      increase of >=3 units increased risks of GDM (RR: 1.71, 95% CI, 1.52-1.93), PE
      (RR: 1.60, 95% CI, 1.33-1.94), GHtn (RR: 1.66, 95% CI, 1.42-1.94), and primary
      cesarean delivery (RR: 1.29, 95% CI, 1.12-1.49) and decreased the risk of a
      successful VBAC (RR: 0.89; 95% CI, 0.80-0.99) compared to women with
      interpregnancy BMI change within -1 and +1 unit. GDM was also increased among
      women increasing their BMI by >=2 but <3 units (RR: 1.40; 95% CI, 1.21-1.61) and
      among those gaining >=1 but <2 units (RR: 1.23; 95% CI, 1.08-1.40). CONCLUSION:
      An interpregnancy BMI increase of >=3 units is associated with an increased risk
      of all outcomes. These findings emphasize the importance of interpregnancy weight
      management.

PMID- 29033121
TI  - Prognostic significance of extranodal extension in head and neck squamous cell
      carcinoma cN0 patients with occult metastatic neck nodes.
AB  - INTRODUCTION AND OBJECTIVES: Extranodal extension in nodal metastases is an
      independent adverse prognostic factor in head and neck squamous cell carcinoma
      patients. However, few studies specifically address the subgroup of patients with
      no clinical evidence of nodal disease. MATERIAL AND METHODS: We retrospectively
      analysed data from 348 head and neck squamous cell carcinoma patients without any
      previous treatment and lacking clinical or radiological evidence of neck node
      metastases during the initial workup, treated with an elective neck dissection
      between 1992-2014. The incidence of occult metastatic neck nodes with extranodal
      extension and the impact of extranodal extension in survival were evaluated.
      RESULTS: The proportion of patients with occult neck node metastases was 33%. Of
      these, 23.5% had at least one metastatic neck node with extranodal extension.
      There were significant differences in the disease-specific survival rate
      according to neck node status. Five-year disease-specific survival for patients
      without histopathological metastases was 90%, for patients with occult neck node
      metastases without extranodal extension it was 71.2%, and for patients with
      occult neck node metastases with extranodal extension it was 25.9% (P=.0001). The
      multivariate analysis revealed that the presence of occult node metastases with
      extranodal extension was the factor with strongest impact on survival. The
      inclusion of the extranodal extension as a criterion of histopathological
      evaluation in the 8th TNM classification edition improves the prognostic capacity
      compared to previous TNM editions. CONCLUSIONS: Appearance of metastatic neck
      nodes with extranodal extension is an adverse prognostic factor in head and neck
      squamous cell carcinoma patients without clinical evidence of regional disease
      during the initial workup of the tumour.

PMID- 29033120
TI  - Heart rate variability and lifetime risk of cardiovascular disease: the
      Atherosclerosis Risk in Communities Study.
AB  - PURPOSE: The purpose of this study was to estimate the heart rate variability
      (HRV)-related lifetime cardiovascular disease (CVD) risk. METHODS: We followed
      9744 participants without baseline CVD and used a life-table approach to estimate
      lifetime CVD risk (coronary heart disease, heart failure, and stroke) from 45
      through 85 years according to several HRV measures (the SD of RR intervals
      [SDNN], the root mean square of successive differences of successive RR
      intervals, the mean of all normal RR intervals [meanNN], low-frequency [LF] and
      high-frequency [HF] power, and the LF/HF ratio). RESULTS: During 192,110 person
      years of follow-up, we documented 2856 CVD events. Cox regression analyses with
      the false discovery rate method correction showed independent associations of
      SDNN, meanNN, LF, and LF/HF in women with CVD. Lifetime CVD risks in the lowest
      compared with the highest tertile were significantly increased in men for LF/HF
      (51.3% [95% confidence interval, 47.3-54.7] vs. 43.9% [40.1-47.2]), and in women
      for SDNN (39.4% [36.0-43.0] vs. 29.9% [26.3-33.0]), meanNN (39.3% [35.7-42.7] vs.
      28.9% [25.7-31.7]), LF (39.4% [35.9-43.0] vs. 30.0% [26.2-33.2]), and LF/HF
      (37.6% [33.9-40.9] vs. 30.0% [26.8-32.7]). CONCLUSIONS: Greater HRV was modestly
      associated with lower lifetime CVD risk.

PMID- 29033122
TI  - Comments on the assessment of nasal obstruction with rhinomanometry and
      subjective scales and outcomes of surgical and medical treatment.

PMID- 29033123
TI  - Diagnosis and treatment of otitis media with effusion: CODEPEH recommendations.
AB  - The incidence and the prevalence rates of otitis media with effusion (OME) are
      high. However, there is evidence that only a minority of professionals follow the
      recommendations provided in clinical practice guidelines. For the purpose of
      improving diagnosis and treatment of OME in children to prevent and/or reduce its
      impact on children's development, the Commission for the Early Detection of
      Deafness (CODEPEH) has deeply reviewed the scientific literature on this field
      and has drafted a document of recommendations for a correct clinical reaction to
      of OME, including diagnosis and medical and surgical treatment methodology. Among
      others, medication, in particular antibiotics and corticoids, should not be
      prescribed and 3 months of watchful waiting should be the first adopted measure.
      If OME persists, an ENT doctor should assess the possibility of sugical
      treatment. The impact of OME in cases of children with a comorbidity is higher,
      so it requires immediate reaction, without watchful waiting.

PMID- 29033124
TI  - Analysis of audiometric relapse-free survival in patients with immune-mediated
      hearing loss exclusively treated with corticosteroids.
AB  - OBJECTIVE: To describe the results in terms of audiometric relapse-free survival
      and relapse rate in immunomediated hearing loss patients treated exclusively with
      corticosteroids. METHOD: Retrospective study of patients with audiometric
      relapses, monitored from 1995 to 2014, in two centres of the Community of Madrid.
      RESULTS: We evaluated 31 patients with a mean age of 48.52 years (14.67 SD), of
      which 61.3% were women. Most hearing loss was fluctuating (48.4%). Only 16.1% of
      patients had systemic autoimmune disease. There is a moderate positive
      correlation between the sex variable and the systemic involvement variable
      (Spearman's correlation coefficient=0.356): specifically, between being female
      and systemic disease. The relative incidence rate of relapse in the first year
      was 2.01 relapses/year with a 95% CI (1.32 to 2.92). The mean survival time of
      the event (audiometric relapse) was 5.25 months (SD 0.756). With multivariate
      analysis, the only variable that achieved statistical significance was age, with
      a hazard ratio of 1.032 (95% CI; 1.001-1.063, P=.043). CONCLUSIONS: Immune
      mediated disease of the inner ear is a chronic disease with relapses. Half of the
      patients with immunomediated hearing loss treated exclusively with
      corticosteroids relapse before 6 months of follow-up. In addition, if a patient
      has not relapsed, they are more likely to relapse as each year passes. Analysis
      of the of audiometric relapse- free survival will enable the effect of future
      treatments to be compared and their capacity to reduce the rhythm of relapses.

PMID- 29033125
TI  - Mammary analogue secretory carcinoma of salivary glands: Report of clinical case.

PMID- 29033126
TI  - Vertigo and dizziness in hospital: Attendance, flow and characteristics of
      patients.
AB  - INTRODUCTION AND OBJECTIVES: Vertigo and dizziness as symptoms are frequent in
      the population. They are present in a wide range of pathologies and it is usually
      difficult to make an accurate diagnosis. The general objective of this study is
      to obtain the information to evaluate vertigo and dizziness in the hospital
      setting. The specific objectives are: to estimate the burden of these symptoms at
      the hospital; to study patients' conditions and to detail the flow of these
      patients inside the hospital. METHODS: Observational descriptive study. We made a
      search of the referral proposals made in 2011 and 2012 to the hospital because of
      vertigo symptoms. The patients' demographic and clinical characteristics, and the
      administrative details of the referrals were analysed. RESULTS: A total of 558
      proposals were analysed corresponding to 494 patients. Vertigo accounted for 0.5%
      of all referrals made from Primary Care to the hospital. Sixty-three percent of
      the sample were women; the average age was 58 years. Eighty-eight percent of the
      patients were evaluated by Otorhinolaryngology, 24% by Neurology. Thirty point
      eight percent consulted on 3 or more occasions for the symptom. Sixteen percent
      were assessed for psychiatric conditions in the hospital. CONCLUSIONS: Vertigo as
      a symptom is a significant burden in the hospital setting. The patients who
      suffer it consult on several occasions and are assessed by different specialties.
      This implies in some cases an excessive and ineffective flow of patients. In our
      setting, otorhinolaryngology is the main department to treat vertigo and
      dizziness patients.

PMID- 29033127
TI  - Mechanism of Transcription Anti-termination in Human Mitochondria.
AB  - In human mitochondria, transcription termination events at a G-quadruplex region
      near the replication origin are thought to drive replication of mtDNA by
      generation of an RNA primer. This process is suppressed by a key regulator of
      mtDNA-the transcription factor TEFM. We determined the structure of an anti
      termination complex in which TEFM is bound to transcribing mtRNAP. The structure
      reveals interactions of the dimeric pseudonuclease core of TEFM with mobile
      structural elements in mtRNAP and the nucleic acid components of the elongation
      complex (EC). Binding of TEFM to the DNA forms a downstream "sliding clamp,"
      providing high processivity to the EC. TEFM also binds near the RNA exit channel
      to prevent formation of the RNA G-quadruplex structure required for termination
      and thus synthesis of the replication primer. Our data provide insights into
      target specificity of TEFM and mechanisms by which it regulates the switch
      between transcription and replication of mtDNA.

PMID- 29033128
TI  - The DNA Inflammasome in Human Myeloid Cells Is Initiated by a STING-Cell Death
      Program Upstream of NLRP3.
AB  - Detection of cytosolic DNA constitutes a central event in the context of numerous
      infectious and sterile inflammatory conditions. Recent studies have uncovered a
      bipartite mode of cytosolic DNA recognition, in which the cGAS-STING axis
      triggers antiviral immunity, whereas AIM2 triggers inflammasome activation. Here,
      we show that AIM2 is dispensable for DNA-mediated inflammasome activation in
      human myeloid cells. Instead, detection of cytosolic DNA by the cGAS-STING axis
      induces a cell death program initiating potassium efflux upstream of NLRP3.
      Forward genetics identified regulators of lysosomal trafficking to modulate this
      cell death program, and subsequent studies revealed that activated STING traffics
      to the lysosome, where it triggers membrane permeabilization and thus lysosomal
      cell death (LCD). Importantly, the cGAS-STING-NLRP3 pathway constitutes the
      default inflammasome response during viral and bacterial infections in human
      myeloid cells. We conclude that targeting the cGAS-STING-LCD-NLRP3 pathway will
      ameliorate pathology in inflammatory conditions that are associated with
      cytosolic DNA sensing.

PMID- 29033129
TI  - Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage
      Restriction.
AB  - Progenitor cells differentiate into specialized cell types through coordinated
      expression of lineage-specific genes and modification of complex chromatin
      configurations. We demonstrate that a histone deacetylase (Hdac3) organizes
      heterochromatin at the nuclear lamina during cardiac progenitor lineage
      restriction. Specification of cardiomyocytes is associated with reorganization of
      peripheral heterochromatin, and independent of deacetylase activity, Hdac3
      tethers peripheral heterochromatin containing lineage-relevant genes to the
      nuclear lamina. Deletion of Hdac3 in cardiac progenitor cells releases genomic
      regions from the nuclear periphery, leading to precocious cardiac gene expression
      and differentiation into cardiomyocytes; in contrast, restricting Hdac3 to the
      nuclear periphery rescues myogenesis in progenitors otherwise lacking Hdac3. Our
      results suggest that availability of genomic regions for activation by lineage
      specific factors is regulated in part through dynamic chromatin-nuclear lamina
      interactions and that competence of a progenitor cell to respond to
      differentiation signals may depend upon coordinated movement of responding gene
      loci away from the nuclear periphery.

PMID- 29033131
TI  - Oxysterol Restraint of Cholesterol Synthesis Prevents AIM2 Inflammasome
      Activation.
AB  - Type I interferon restrains interleukin-1beta (IL-1beta)-driven inflammation in
      macrophages by upregulating cholesterol-25-hydroxylase (Ch25h) and repressing
      SREBP transcription factors. However, the molecular links between lipid
      metabolism and IL-1beta production remain obscure. Here, we demonstrate that
      production of 25-hydroxycholesterol (25-HC) by macrophages is required to prevent
      inflammasome activation by the DNA sensor protein absent in melanoma 2 (AIM2). We
      find that in response to bacterial infection or lipopolysaccharide (LPS)
      stimulation, macrophages upregulate Ch25h to maintain repression of SREBP2
      activation and cholesterol synthesis. Increasing macrophage cholesterol content
      is sufficient to trigger IL-1beta release in a crystal-independent but AIM2
      dependent manner. Ch25h deficiency results in cholesterol-dependent reduced
      mitochondrial respiratory capacity and release of mitochondrial DNA into the
      cytosol. AIM2 deficiency rescues the increased inflammasome activity observed in
      Ch25h-/-. Therefore, activated macrophages utilize 25-HC in an anti-inflammatory
      circuit that maintains mitochondrial integrity and prevents spurious AIM2
      inflammasome activation.

PMID- 29033130
TI  - Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab.
AB  - The mechanisms by which immune checkpoint blockade modulates tumor evolution
      during therapy are unclear. We assessed genomic changes in tumors from 68
      patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab
      naive, before and after nivolumab initiation (CA209-038 study). Tumors were
      analyzed by whole-exome, transcriptome, and/or T cell receptor (TCR) sequencing.
      In responding patients, mutation and neoantigen load were reduced from baseline,
      and analysis of intratumoral heterogeneity during therapy demonstrated
      differential clonal evolution within tumors and putative selection against
      neoantigenic mutations on-therapy. Transcriptome analyses before and during
      nivolumab therapy revealed increases in distinct immune cell subsets, activation
      of specific transcriptional networks, and upregulation of immune checkpoint genes
      that were more pronounced in patients with response. Temporal changes in
      intratumoral TCR repertoire revealed expansion of T cell clones in the setting of
      neoantigen loss. Comprehensive genomic profiling data in this study provide
      insight into nivolumab's mechanism of action.

PMID- 29033134
TI  - Biochemical methane potential (BMP) tests: Reducing test time by early parameter
      estimation.
AB  - Biochemical methane potential (BMP) test is a key analytical technique to assess
      the implementation and optimisation of anaerobic biotechnologies. However, this
      technique is characterised by long testing times (from 20 to >100days), which is
      not suitable for waste utilities, consulting companies or plants operators whose
      decision-making processes cannot be held for such a long time. This study
      develops a statistically robust mathematical strategy using sensitivity functions
      for early prediction of BMP first-order model parameters, i.e. methane yield (B0)
      and kinetic constant rate (k). The minimum testing time for early parameter
      estimation showed a potential correlation with the k value, where (i) slowly
      biodegradable substrates (k<=0.1d-1) have a minimum testing times of >=15days,
      (ii) moderately biodegradable substrates (0.1<k<0.2d-1) have a minimum testing
      times between 8 and 15 days, and (iii) rapidly biodegradable substrates (k>=0.2d
      1) have testing times lower than 7days.

PMID- 29033132
TI  - Assembly and Function of Heterotypic Ubiquitin Chains in Cell-Cycle and Protein
      Quality Control.
AB  - Posttranslational modification with ubiquitin chains controls cell fate in all
      eukaryotes. Depending on the connectivity between subunits, different ubiquitin
      chain types trigger distinct outputs, as seen with K48- and K63-linked conjugates
      that drive protein degradation or complex assembly, respectively. Recent
      biochemical analyses also suggested roles for mixed or branched ubiquitin chains,
      yet without a method to monitor endogenous conjugates, the physiological
      significance of heterotypic polymers remained poorly understood. Here, we
      engineered a bispecific antibody to detect K11/K48-linked chains and identified
      mitotic regulators, misfolded nascent polypeptides, and pathological Huntingtin
      variants as their endogenous substrates. We show that K11/K48-linked chains are
      synthesized and processed by essential ubiquitin ligases and effectors that are
      mutated across neurodegenerative diseases; accordingly, these conjugates promote
      rapid proteasomal clearance of aggregation-prone proteins. By revealing key roles
      of K11/K48-linked chains in cell-cycle and quality control, we establish
      heterotypic ubiquitin conjugates as important carriers of biological information.

PMID- 29033135
TI  - One-year recombinant growth hormone therapy does not improve hemoglobin state and
      morphology of erythrocytes in growth hormone deficient children.
AB  - An increase in growth rates of children suffering from growth hormone deficiency
      (GHD) subjected to recombinant growth hormone treatment (rGHT) was shown to be
      accompanied by acceleration of metabolic processes that may stimulate oxygen
      consumption in various organs and tissues. Therefore, oxygen-transporting
      properties of RBC should undergo considerable changes during the rGHT. The aim of
      this study was to examine the effects of rGHT on erythrocyte shape and hemoglobin
      state in GHD children. The level of oxyhemoglobin (Oxy-Hb) in RBC was analyzed by
      Raman spectroscopy. The RBC count, mean corpuscular hemoglobin (MCH), mean
      corpuscular volume (MCV) and other parameters were calculated. The blood of
      eleven treatment-naive prepubertal children with GHD (aged 3-9, median 5.7 years)
      was examined and compared with control group (aged 5-7; median 6.0 years) at
      three time points: 0, 3 and 12 months of rGHT. Before rGHT, the MI in GHD
      children was higher (median 0.48 vs 0.14 p=0.0018) and the RBC count was lower
      (median 4.20 vs 4.96 1012 cells/L p=0.0022) than in control group. After the
      treatment, cell count in GHD patients did not differ significantly from the
      control group, but Oxy-Hb level became higher (median 0.64 vs 0.41 p=0.0075).
      During rGHT, MCV decreased (median 80.3 vs 83.2MUm3 p=0.0231). Morphological and
      functional characteristics of erythrocytes in GHD children were shown to differ
      significantly from the healthy control group. A twelve-month rGHT partially
      improved some of the studied parameters but Oxy-Hb level and echinocyte count
      remained high.

PMID- 29033136
TI  - Diets of mammalian fossil fauna from Kanapoi, northwestern Kenya.
AB  - Carbon isotope ratios of mammalian teeth from the Kanapoi site in northern Kenya
      are interpreted in the context of C3 and C4 derived resources to investigate the
      paleoecology of Australopithecus anamensis. delta13C values of large mammals,
      when compared at the taxon level, show an ecosystem that is strongly biased
      towards mixed feeders and browsers. However, sufficient C4 resources were present
      such that some C4 dominated grazers were also present in the large mammal fauna.
      Analyses of micromammals shows that their diets were C3 dominated or C3-C4 mixed.
      Carbon isotope studies of primates shows that the major primate tribes-Colobini,
      Papioini, Hominini-all made some use of C4 resources in their respective diets;
      the Hominini had a higher fraction of C3 diet resources than the other primate
      tribes represented in the fossil record.

PMID- 29033133
TI  - Natively Unfolded FG Repeats Stabilize the Structure of the Nuclear Pore Complex.
AB  - Nuclear pore complexes (NPCs) are ~100 MDa transport channels assembled from
      multiple copies of ~30 nucleoporins (Nups). One-third of these Nups contain
      phenylalanine-glycine (FG)-rich repeats, forming a diffusion barrier, which is
      selectively permeable for nuclear transport receptors that interact with these
      repeats. Here, we identify an additional function of FG repeats in the structure
      and biogenesis of the yeast NPC. We demonstrate that GLFG-containing FG repeats
      directly bind to multiple scaffold Nups in vitro and act as NPC-targeting
      determinants in vivo. Furthermore, we show that the GLFG repeats of Nup116
      function in a redundant manner with Nup188, a nonessential scaffold Nup, to
      stabilize critical interactions within the NPC scaffold needed for late steps of
      NPC assembly. Our results reveal a previously unanticipated structural role for
      natively unfolded GLFG repeats as Velcro to link NPC subcomplexes and thus add a
      new layer of connections to current models of the NPC architecture.

PMID- 29033137
TI  - The global problem of early deaths in acute promyelocytic leukemia: A strategy to
      decrease induction mortality in the most curable leukemia.
AB  - Acute promyelocytic leukemia (APL) is a hyper-acute illness and presents with
      profound cytopenias in most patients and disseminated intravascular coagulation
      (DIC). Excellent treatment options are now available with drugs such as all-trans
      retinoic acid (ATRA), arsenic trioxide (ATO), anthracyclines and cytarabine. The
      outcome in APL has improved tremendously in the last 50years due to better
      understanding of the disease, development of effective targeted agents and
      improvement in supportive care. Carefully selected groups of patients treated in
      large multi-center trials on a protocol and in experienced centers have shown
      survival rates in excess of 85%. However population data and other studies show
      that approximately 30% of patients die during induction. This is an
      Institutional, national and global problem and remains a pressing and frustrating
      challenge in APL. While most APL experts are aware of the high rate of early
      deaths (ED), such awareness is not typically present among general hematologists
      and oncologists. Our area of focus over the last 7years has been the reduction of
      ED in both academic and community centers; as a result we have acquired
      substantial experience in APL induction. Two centers have implemented population
      wide prospective trials; Brazil and Georgia/South Carolina, USA with improvement
      in the ED rate. Both centers used standardized guidelines along with consultative
      support and sharing of expertise which proved effective and helped to decrease
      ED. Induction mortality in APL is 30% or greater. We believe ED is largely
      preventable and population-wide survival can be improved. An effective strategy
      is to utilize a set of simplified treatment guidelines coupled with support from
      a group of experts during induction. Treating oncologists in both academic and
      community hospitals should receive aggressive education about ED and be
      encouraged to seek advice from a core group of established APL experts. This
      model could be implemented nationally to improve population-wide survival in this
      most curable leukemia.

PMID- 29033139
TI  - The Problem with Diagnosis of Intestinal Schistosomiasis.

PMID- 29033138
TI  - Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects
      of Escitalopram in Social Anxiety Disorder: A Randomized Trial.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are commonly
      prescribed for depression and anxiety, but their efficacy relative to placebo has
      been questioned. We aimed to test how manipulation of verbally induced
      expectancies, central for placebo, influences SSRI treatment outcome and brain
      activity in patients with social anxiety disorder (SAD). METHODS: We did a
      randomized clinical trial, within an academic medical center (Uppsala, Sweden),
      of individuals fulfilling the DSM-IV criteria for SAD, recruited through media
      advertising. Participants were 18years or older and randomized in blocks, through
      a computer-generated sequence by an independent party, to nine weeks of overt or
      covert treatment with escitalopram (20mg daily). The overt group received correct
      treatment information whereas the covert group was treated deceptively with the
      SSRI described, by the psychiatrist, as active placebo. The treating psychiatrist
      was necessarily unmasked while the research staff was masked from intervention
      assignment. Treatment efficacy was assessed primarily with the self-rated
      Liebowitz Social Anxiety Scale (LSAS-SR), administered at week 0, 1, 3, 6 and 9,
      also yielding a dichotomous estimate of responder status (clinically significant
      improvement). Before and at the last week of treatment, brain activity during an
      emotional face-matching task was assessed with functional magnetic resonance
      imaging (fMRI) and during fMRI sessions, anticipatory speech anxiety was also
      assessed with the Spielberger State-Trait Anxiety Inventory - State version (STAI
      S). Analyses included all randomized patients with outcome data at posttreatment.
      This study is registered at ISRCTN, number 98890605. FINDINGS: Between March 17th
      2014 and May 22nd 2015, 47 patients were recruited. One patient in the covert
      group dropped out after a few days of treatment and did not provide fMRI data,
      leaving 46 patients with complete outcome data. After nine weeks of treatment,
      overt (n=24) as compared to covert (n=22) SSRI administration yielded
      significantly better outcome on the LSAS-SR (adjusted difference 21.17, 95% CI
      10.69-31.65, p<0.0001) with more than three times higher response rate (50% vs.
      14%; chi2(1)=6.91, p=0.009) and twice the effect size (d=2.24 vs. d=1.13) from
      pre-to posttreatment. There was no significant between-group difference on
      anticipatory speech anxiety (STAI-S), both groups improving with treatment. No
      serious adverse reactions were recorded. On fMRI outcomes, there was suggestive
      evidence for a differential neural response to treatment between groups in the
      posterior cingulate, superior temporal and inferior frontal gyri (all z
      thresholds exceeding 3.68, p<=0.001). Reduced social anxiety with treatment
      correlated significantly with enhanced posterior cingulate (z threshold 3.24,
      p=0.0006) and attenuated amygdala (z threshold 2.70, p=0.003) activity.
      INTERPRETATION: The clinical and neural effects of escitalopram were markedly
      influenced by verbal suggestions. This points to a pronounced placebo component
      in SSRI-treatment of SAD and favors a biopsychosocial over a biomedical
      explanatory model for SSRI efficacy. FUNDING RESOURCES: The Swedish Research
      Council for Working Life and Social Research (grant 2011-1368), the Swedish
      Research Council (grant 421-2013-1366), Riksbankens Jubileumsfond - the Swedish
      Foundation for Humanities and Social Sciences (grant P13-1270:1).

PMID- 29033140
TI  - The Interplay of Protein Coding and Non-Coding RNAs (circRNAs, lncRNAs) During
      Cardiac Differentiation.

PMID- 29033141
TI  - Discussion of: "Not every trauma patient with a radiographic head injury requires
      transfer for neurosurgical evaluation: Application of the brain injury guidelines
      to patients transferred to a level 1 trauma center".

PMID- 29033143
TI  - Measurement and reporting of pressure ulcer related harm in NHS Hospitals in
      England.

PMID- 29033142
TI  - Discussion of: "Re-excision rates after breast conserving surgery following the
      2014 SSO-ASTRO guidelines".

PMID- 29033144
TI  - Impaired anti-inflammatory activity of PPARgamma in the salivary epithelia of
      Sjogren's syndrome patients imposed by intrinsic NF-kappaB activation.
AB  - Sjogren's syndrome (SS) patients manifest inflammation in the salivary glands
      (SG) and evidence of persistent intrinsic activation of ductal SG epithelial
      cells (SGEC), demonstrable in non-neoplastic SGEC lines derived from patients (SS
      SGEC). The peroxisome-proliferator-activated receptor-gamma (PPARgamma) mediates
      important anti-inflammatory activities in epithelial cells. Herein, the
      comparative analysis of SG biopsies and SGEC lines obtained from SS patients and
      controls had revealed constitutively reduced PPARgamma expression,
      transcriptional activity and anti-inflammatory function in the ductal epithelia
      of SS patients that were associated with cell-autonomously activated NF-kappaB
      and IL-1beta pathways. Transcriptome profiling analysis revealed several
      differentially expressed proinflammatory and metabolism-related gene sets in SS
      SGEC lines. These aberrations largely correlated with the severity of
      histopathologic lesions, the disease activity and the occurrence of adverse
      manifestations in SS patients studied, a fact which corroborates the key role of
      the persistently-activated epithelia in the pathogenesis of both local and
      systemic features of this disease. The treatment of control SGEC lines with
      PPARgamma agonists was found to diminish the NF-kappaB activation and apoptosis
      induced by proinflammatory agents. In addition, the in-vitro application of
      PPARgamma agonists and pharmacologic inhibitors of IL-1beta and NF-kappaB had
      significant beneficial effects on SS-SGEC lines, such as the restoration of
      PPARgamma functions and the reduction of their intrinsic activation, a fact which
      may advocate the future clinical study of the above agents as therapeutic
      modalities for SS.

PMID- 29033145
TI  - A novel optimization algorithm for MIMO Hammerstein model identification under
      heavy-tailed noise.
AB  - In this paper, we study the system identification of multi-input multi-output
      (MIMO) Hammerstein processes under the typical heavy-tailed noise. To the best of
      our knowledge, there is no general analytical method to solve this identification
      problem. Motivated by this, we propose a general identification method to solve
      this problem based on a Gaussian-Mixture Distribution intelligent optimization
      algorithm (GMDA). The nonlinear part of Hammerstein process is modeled by a
      Radial Basis Function (RBF) neural network, and the identification problem is
      converted to an optimization problem. To overcome the drawbacks of analytical
      identification method in the presence of heavy-tailed noise, a meta-heuristic
      optimization algorithm, Cuckoo search (CS) algorithm is used. To improve its
      performance for this identification problem, the Gaussian-mixture Distribution
      (GMD) and the GMD sequences are introduced to improve the performance of the
      standard CS algorithm. Numerical simulations for different MIMO Hammerstein
      models are carried out, and the simulation results verify the effectiveness of
      the proposed GMDA.

PMID- 29033146
TI  - The prevalence and performance of resistance exercise training activities in an
      Australian population in relation to health authority guidelines.
AB  - OBJECTIVES: Resistance training research highlights the importance of training
      intensity to resistance exercise training (RET) and the associated benefits to
      health and function for healthy and at-risk populations. The American College of
      Sports Medicine (ACSM) recommend specific intensities, frequencies, repetitions,
      and number of exercises of RET to be performed to maintain health. The primary
      aim of this study was to describe the prevalence of achieving recommended levels
      of RET in relation to ACSM guidelines for intensity, frequency, repetitions, and
      number of exercises in a regional Australian population. DESIGN: A Computer
      Assisted-Telephone-Interview (CATI) survey (n=1237) was conducted to determine
      RET participation. METHODS: Participants were 18 years plus, residing in Central
      Queensland, Australia. RESULTS: The prevalence of respondents performing 'No
      RET', 'insufficient RET' and 'sufficient RET' were 79.6.0%, 15.2% and 5.2%
      respectively. Significantly higher proportions of younger adults adhered to all
      RET guidelines for intensity (19.2 vs 8.1%), frequency (19.9 vs 11.6%),
      repetitions (17.8 vs 6.3%), and number of exercises (8.2 vs 3.6%) (p<0.05).
      Significantly higher proportions of males, younger adults (18-34 years), higher
      educated individuals (>15 years), and individuals engaging in sufficient levels
      of aerobic exercise training (AET) engaged in sufficient levels of RET (p<0.05).
      CONCLUSIONS: The prevalence of Australian's participating in regular RET programs
      is low and only a small proportion of participants meet ACSM guidelines for the
      quantity and quality of RET that is likely to provide health benefits. This has
      implications for public health policy and the future development and promotion of
      population-level RET guidelines.

PMID- 29033147
TI  - Apparent Diffusion Coefficient Value to Evaluate Tumor Response After Neoadjuvant
      Chemotherapy in Patients with Breast Cancer.
AB  - RATIONALE AND OBJECTIVES: This study explored tumor behavior in patients with
      breast cancer during neoadjuvant chemotherapy (NAC) by sequential measurements of
      tumor apparent diffusion coefficient (ADC) after each chemotherapy cycle. The aim
      was to determine if the tumor ADC is useful to differentiate complete
      pathological response (cPR) from partial pathological response (pPR) during NAC.
      MATERIALS AND METHODS: A total of 16 cases (in 14 patients) with diagnosis of
      breast cancer eligible to receive NAC were included. There were 70 magnetic
      resonance imaging examinations performed, 5 for each patient, during NAC cycles.
      Diffusion-weighted imaging was performed on a 1.5T system (b values of 0 and
      700s/mm2). Four ADC ratios between the five MRI examinations were obtained to
      assess ADC changes during NAC. Absence of invasive breast cancer at surgical
      specimens (Miller-Payne 5) was considered as cPR and was used as reference for
      ADC cutoff ratios. RESULTS: In this study, we were able to differentiate between
      cPR and pPR, after two cycles of NAC until the end of NAC before surgery (ADC
      ratios 2-4). The thresholds to differentiate between cPR and pPR of ADC ratios 2,
      3, and 4, were 1.14 * 10-3mm2/s, 1.08 * 10-3mm2/s, and 1.25 * 10-3mm2/s,
      respectively, and have a cross-validated sensitivity and specificity of 79.2%,
      79.7% (ADC ratio 2); 100%, 66.7% (ADC ratio 3); and 100%, 83.8% (ADC ratio 4),
      respectively. CONCLUSIONS: The ADC ratios were useful to differentiate cPR from
      pPR in breast cancer tumors after NAC. Thus, it may be useful in tailoring
      treatment in these patients.

PMID- 29033148
TI  - Medial approach for minimally-invasive harvesting of a deep circumflex iliac
      artery flap for reconstruction of the jaw using virtual surgical planning and
      CAD/CAM technology.
AB  - Donor site morbidity is the most common limitation of the deep circumflex iliac
      artery (DCIA) flap, so the purpose of this paper is to describe a new, minimally
      invasive, approach to its harvest using virtual surgical planning and CAD/CAM
      technology to reduce functional and aesthetic morbidity at the donor site.
      Virtual surgical planning was based on preoperative computed tomographic data. A
      newly-designed surgical guide made using CAD/CAM technology was used to transfer
      the virtual surgical plan to the site of operation. This enabled us to raise a
      bicortical flap from the pelvis with preservation of the anterior superior iliac
      crest from the medial side with minimal muscular stripping. The guide, designed
      at slightly less than 90 degrees  to the lateral cortex, allowed the cut segment
      of bone to be raised medially. The new virtual surgical planning guide allowed a
      medial approach with reduced stripping of muscle and lower morbidity. No
      complications were encountered during the operation or the healing phase.
      Patients treated in this way had a shorter recovery period, with minimal
      complaints about walking or loss of profile of the hip. We conclude that virtual
      surgical planning can aid a minimally-invasive approach with predictable results.
      This allows a medial approach to the harvest of DCIA with preservation of
      important anatomical structures, and a reduction in donor site morbidity.

PMID- 29033149
TI  - Management of cervicofacial infections: a survey of current practice in
      maxillofacial units in the UK.
AB  - Cervicofacial infections are common emergency presentations to maxillofacial
      departments in the UK, there is no consensus about their management and, in
      particular, the role of corticosteroids is not clear. Our aim was to find out the
      current practice of UK maxillofacial surgeons in managing these infections using
      a multicentre questionnaire study. The questionnaire was designed, piloted, and
      revised before distribution, and questions were asked to assess preoperative,
      operative, and postoperative management. It was distributed to maxillofacial
      surgeons throughout the UK through the Maxillofacial Research Trainee
      Collaborative (MTReC) network, and at the 2016 British Association of Oral and
      Maxillofacial Surgeons (BAOMS) Junior Trainees Group conference. A total of 350
      questionnaires were distributed to 17 maxillofacial units. Eighty-six
      questionnaires were distributed at the BAOMS Junior Trainee conference. An
      overall response rate of 92% (n=324) was achieved. The results showed that there
      were important differences in reported practice between and within maxillofacial
      units in the UK in managing these infections. The antibiotic regimens and use of
      steroids varied widely. Twenty-three per cent of respondents had to wait over
      24hours for access to emergency theatres. However, these results provide no hard
      evidence for or against the use of corticosteroids in cervicofacial infections.

PMID- 29033150
TI  - Extraction of triazole fungicides in environmental waters utilizing poly (ionic
      liquid)-functionalized magnetic adsorbent.
AB  - This work prepared a new poly (ionic liquid)-functionalized magnetic adsorbent
      (PFMA) for the extraction of triazole fungicides (TFs) in environmental waters
      prior to determination by high performance liquid chromatography/diode array
      detection (HPLC-DAD). A polymerizable ionic liquid, 1-methyl-3-allylimidazolium
      bis(trifluoromethylsulfonyl)imide was employed to copolymerize with
      divinylbenzene on the surface of modified magnetite to fabricate the PFMA. The
      morphology, spectroscopic and magnetic properties of the new adsorbent were
      investigated by different techniques. A series of key parameters that influence
      the extraction performance including the amount of PFMA, desorption solvent,
      adsorption and desorption time, sample pH value and ionic strength were optimized
      in detail. Under the optimum conditions, the prepared PFMA could extract targeted
      TFs effectively and quickly under the format of magnetic solid-phase extraction
      (MSPE). Satisfactory linearities were achieved in the range of 0.1-200.0MUg/L for
      triadimenol and 0.05-200.0MUg/L for other TFs with good coefficients of
      determination above 0.99 for all analytes. The limits of detection (S/N=3) and
      limits of quantification (S/N=10) for TFs were in the range of 0.0050-0.0078MUg/L
      and 0.017-0.026MUg/L, respectively. Environmental waters including lake, river
      and well waters were used to demonstrate the applicability of developed MSPE-HPLC
      DAD method, and satisfactory recoveries and repeatability were obtained.

PMID- 29033151
TI  - Is it adequate to carry out a chest-CT in patients with mild-moderate chest
      trauma?
AB  - Mild-moderate blunt chest trauma is defined as a blunt chest trauma that is not
      caused by a high-energy mechanism, causing thoracic tenderness with or without
      rib fractures and that has no immediate life-threatening consequences for the
      patient. It is a frequent clinical situation in the emergency department. The
      most common radiological techniques that are used in this context are chest X-ray
      and thoracic computed tomography (CT). The CT scan is set as the gold standard.
      However, there are no current clinical-radiological guidelines that establish the
      adequacy of the requests of the CT scan. Therefore, we decided to search for
      evidence-based recommendations to improve the adequacy of the chest X-ray and CT
      scan in our daily practice in order to reduce the costs and avoid unnecessary
      radiation exposure.

PMID- 29033152
TI  - Intraoperative Infiltration of Liposomal Bupivacaine vs Bupivacaine Hydrochloride
      for Pain Management in Primary Total Hip Arthroplasty: A Prospective Randomized
      Trial.
AB  - BACKGROUND: Pain management after total hip arthroplasty is well studied.
      Nevertheless, there is no consensus regarding the "cocktail" to use in
      periarticular infiltration (PAI). Liposomal bupivacaine (LB) is a slow release
      local anesthetic that can be infiltrated during surgery. In this study, we
      compared LB to bupivacaine hydrochloride (HCL). METHODS: Between September 2014
      and March 2016, 181 patients were screened for this prospective randomized trial.
      A total of 107 patients were enrolled and studied. Patients were separated into
      LB and control groups. LB group (50) received PAI with LB and bupivacaine HCL
      with epinephrine and the control group (57) received PAI with bupivacaine HCL and
      epinephrine. Patient morphine equivalent consumption, pain score estimated on
      visual analog scale, time to first ambulation greater than 20 feet, time to
      discharge, drug-related side effects, and patient falls were documented. Data
      were collected up to 72 hours postoperation. RESULTS: There was no significant
      difference in morphine equivalent consumption in any of the 12-hour time blocks,
      up to 72 hours. No patient falls were documented in either group. Time to first
      ambulation greater than 20 feet, ambulation same day as surgery, time to
      discharge, and drug-related side effects were not significantly different between
      groups. CONLCUSION: Intraoperative PAI with LB did not result in significant
      differences in postoperative opioid consumption, pain scores, opioid-related side
      effects, time to first ambulation, and length of stay up to 72 hours following
      total hip arthroplasty compared to a control group.

PMID- 29033153
TI  - Clinical Outcomes and Survivorship of Lateral Unicompartmental Knee Arthroplasty:
      Does Surgical Approach Matter?
AB  - BACKGROUND: Lateral unicompartmental knee arthroplasty (UKA) has been shown to be
      an effective procedure to treat isolated lateral compartment osteoarthritis with
      excellent long-term survivorship. Whether a medial parapatellar approach or a
      lateral parapatellar approach is superior in lateral UKA is unknown. The purpose
      of this study was to determine if there is a difference in intermediate-term
      clinical outcomes in patients undergoing lateral UKA through a lateral vs medial
      parapatellar approach. METHODS: We retrospectively reviewed a consecutive series
      of 65 patients who underwent lateral UKA with a minimum of 2-year follow-up.
      Fifty-two patients (80%) had a lateral approach and 13 (20%) a medial
      parapatellar approach. Patient demographics, preoperative and postoperative
      radiographic findings, need for revision surgery, Knee Society Score, and range
      of motion were assessed. RESULTS: Overall survivorship was 94% at a mean of 82
      months; with the sample size available for study, there was no difference in
      survivorship between the groups. There was no difference in Knee Society Score or
      revision to total knee arthroplasty (5% vs 7%, P = 1.000) between the medial and
      lateral approach groups. Comparatively, the lateral approach group did have
      significantly greater postoperative flexion (123.6 degrees  vs 116.5 degrees , P
      = .006) and greater improvement in flexion from preoperative measurements (3.0 vs
      -8.0 degrees , P = .010). CONCLUSION: Although our sample size was small, we
      could not demonstrate a difference in revision rates or clinical outcome scores
      when comparing a lateral or a medial approach with lateral UKA at intermediate
      term follow-up. A lateral approach did have greater postoperative flexion, but
      its clinical significance remains undetermined.

PMID- 29033154
TI  - The Use of Porous Tantalum Augments for the Reconstruction of Acetabular Defect
      in Primary Total Hip Arthroplasty.
AB  - BACKGROUND: Given the lack of studies of acetabular defect reconstruction in
      primary total hip arthroplasty (THA) using tantalum augments, this study aims to
      evaluate clinical and radiographic results for treatment with tantalum augments
      to reconstruct acetabular defects in primary THA. METHODS: We retrospectively
      reviewed 19 patients (19 hips) with acetabular defects who underwent primary THA
      using tantalum augments, with a minimum follow-up of 2 years. Clinical,
      radiographic, and surgical data were retrospectively evaluated. RESULTS: Mean
      follow-up was 5.1 years (range 2.5-7.6). Harris Hip Score improved from 35.8
      (range 19-56) preoperatively to 85.3 (63-98) at last follow-up (P < .01). Oxford
      Hip Score, University of California Los Angeles activity scale, and Short Form-12
      score also improved significantly from presurgery to last follow-up. Mean
      operation time and blood loss were 124.7 minutes and 530 mL, respectively. Mean
      hip center position was 2.97 cm (range 2.35-3.58) horizontally and 2.06 cm (1.29
      2.92) vertically, and mean acetabular inclination was 38.9 degrees  (range 27
      degrees -47 degrees ) at last follow-up. These parameters were not significantly
      different from those recorded immediately postoperatively (P > .05). There was no
      aseptic loosening, cup and augment migration, screw breakage, or presence of hip
      infection at last follow-up. All hips were radiographically stable. CONCLUSION:
      Porous tantalum augments combined with titanium shells lead to satisfactory
      clinical and radiographic outcomes for the reconstruction of acetabular defect in
      primary THA at a mean 5.1 years of follow-up. This approach confers anatomical
      cup placement, simple operation, and a high rate of stable fixation.

PMID- 29033156
TI  - Component Fracture in the Kotz Modular Femoral Tibial Reconstruction System: An
      Under-Reported Complication.
AB  - BACKGROUND: Primary bone tumors of the femur are commonly reconstructed using an
      endoprosthesis. Different modes of implant failure have been described, including
      structural failure; although uncommon, this may be an under-reported
      complication. The purpose of this study is to examine the rates and risk factors
      for implant fracture of the Kotz Modular Femoral Tibial Reconstruction system
      (KMFTR). METHODS: Two hundred twenty-one patients (95 women and 126 men) who
      underwent a KMFTR reconstruction were reviewed. Twenty-seven patients (12%)
      sustained a prosthetic fracture. The mean time to fracture was 7 years
      postoperatively. The fractured component most commonly involved the distal femur
      (n = 21) and a screw hole in the stem (n = 12). In patients with stem fractures
      (n = 21), the mean intramedullary stem diameter was 12 mm and the mean
      extramedullary component length was 18 cm. RESULTS: Compared to patients who did
      not fracture, those with a prosthetic fracture had a significantly smaller stem
      diameter (12 vs 14 mm, P = .001) and a significantly longer extramedullary
      component length (18 vs 15 cm, P = .04). There was no difference between the
      preoperative and postoperative Toronto Extremity Salvage Scores (P = .98),
      Musculoskeletal Tumor Society 87 (P = .78), or Musculoskeletal Tumor Society 93
      (P = 1.0) ratings for patients with or without a prosthetic fracture. CONCLUSION:
      This study shows that fracture is an under-reported complication associated with
      the KMFTR stem. We identified an endoprosthetic component fracture rate of 12%.
      Patients with smaller stem diameter and longer resection lengths were more likely
      to sustain a stem fracture. Subsequent revision provides a durable means of
      reconstruction, with no significant loss of patient function.

PMID- 29033155
TI  - Does the Additional Articulation in Retrieved Bipolar Hemiarthroplasty Implants
      Decrease Trunnionosis Compared to Total Hip Arthroplasty?
AB  - BACKGROUND: Trunnionosis at the modular head-neck taper interface in metal-on
      polyethylene total hip arthroplasty (MoP THA) has been shown to occur, and
      represents a potential mode of MoP THA failure. The purpose of the present
      investigation is to elucidate differences in fretting and corrosion at the head
      neck taper interface of prostheses retrieved from bipolar hemiarthroplasty (BH)
      and MoP THA. METHODS: A retrieval analysis of BH and MoP THA prostheses featuring
      a single taper design from a single manufacturer and in vivo for a minimum 2
      years was performed. Fifteen femoral heads of 28-mm diameter and corresponding
      femoral stems retrieved from BH were compared with MoP THA implants matched based
      on time in vivo and head length (28 mm, -3 mm to 28 mm, +8 mm). Fretting and
      corrosion damage scoring was completed under stereomicroscopic visualization.
      RESULTS: Femoral head bore tapers retrieved from BH exhibited decreased overall
      fretting (P = .02), when compared to those retrieved from MoP THA. Total
      corrosion scores for all retrieved implants were positively correlated with
      implantation time (rho = 0.54, P < .02). CONCLUSION: Femoral heads retrieved from
      BH exhibit decreased fretting damage compared to those retrieved from MoP THA.
      The added articulation in BH implants may decrease torque produced at the head
      neck taper junction, thereby decreasing fretting. Increased fretting damage in
      implants from MoP THA is not associated with increased corrosion in 28-mm heads
      of this taper design. The longer a BH or MoP THA prosthesis is implanted, the
      greater the risk of damage due to corrosion.

PMID- 29033157
TI  - Midterm Survivorship After Revision Total Hip Arthroplasty With a Custom
      Triflange Acetabular Component.
AB  - BACKGROUND: Custom triflange acetabular components are being increasingly used
      for the reconstruction of Paprosky type IIIB acetabular defects. However, midterm
      survivorship data are lacking. METHODS: We queried the prospective registries at
      2 high-volume revision centers for patients who had undergone revision total hip
      arthroplasty using a custom triflange component between 2000 and 2011. We
      identified 73 patients with minimum 5-year follow-up. These patients' records
      were reviewed to determine incidence of revision or reoperation, clinical
      performance, and radiographic stability. The mean follow-up was 7.5 years (range
      5-12 years). RESULTS: Fifteen of 73 triflange components (20.5%) were indicated
      for revision during the follow-up period, including 6 for instability (8%) and 8
      for infection (11%). Twelve of 73 patients (16%) underwent reoperation for
      reasons other than failure of the triflange component. The median hip disability
      and osteoarthritis outcome score for joint replacement score at midterm follow-up
      was 85 (interquartile range 73-100). Only 1 of 73 implants was determined to be
      radiographically loose at midterm follow-up. CONCLUSION: Custom triflange
      reconstruction for severe acetabular deficiency is a viable option; however,
      complications are common and significant challenges remain for those that fail.

PMID- 29033158
TI  - Revision Total Knee Arthroplasty for Periprosthetic Joint Infection Is Associated
      With Increased Postoperative Morbidity and Mortality Relative to Noninfectious
      Revisions.
AB  - BACKGROUND: Periprosthetic joint infection (PJI) after primary total knee
      arthroplasty (TKA) is a devastating complication. The short-term morbidity
      profile of revision TKA performed for PJI relative to non-PJI revisions is poorly
      characterized. The purpose of this study is to determine 30-day postoperative
      outcomes after revision TKA for PJI, relative to primary TKA and aseptic revision
      TKA. METHODS: The American College of Surgeons National Surgical Quality
      Improvement Program from 2005 to 2015 was queried for primary and revision TKA
      cases. Revision TKA cases were categorized into PJI and non-PJI cohorts.
      Differences in 30-day outcomes including postoperative complications,
      readmissions, operative time, and length of stay were compared using bivariate
      and multivariate analyses. RESULTS: In total, 175,761 TKAs were included in this
      study, with 162,981 (92.7%) primary TKAs and 12,780 (7.3%) revision TKAs, of
      which 2196 (17.2%) revisions were performed for PJI. When compared to aseptic
      revision TKA, multivariate analysis demonstrated that PJI revisions had a
      significantly higher risk of major early postoperative complications including
      death (adjusted odds ratio [OR] 3.25) and sepsis (OR 8.73). In addition, nonhome
      discharge (OR 1.75), readmissions (OR 1.67), and length of stay (+2.1 days) were
      all greater relative to non-PJI revisions. CONCLUSION: Utilizing a large,
      prospectively collected, national database, we found that revision TKA for PJI
      has a greater risk of short-term morbidity and mortality and requires a higher
      utilization of healthcare resources. These results have implications for patient
      counseling and alternative payment models that may eventually include revision
      TKA.

PMID- 29033159
TI  - Assessing Acute Kidney Injury After First-Stage Joint Revision for Infection.

PMID- 29033160
TI  - Transgender Youth Fertility Attitudes Questionnaire: Measure Development in
      Nonautistic and Autistic Transgender Youth and Their Parents.
AB  - PURPOSE: The objective of this study was to assess transgender youth and parent
      attitudes regarding (1) the potential impact of gender-affirming hormone therapy
      on fertility and (2) fertility preservation (FP) options. METHODS: The
      Transgender Youth Fertility Attitudes Questionnaire was developed through a
      multistage participatory process with gender specialists and key stakeholders
      (transgender youth and their parents, N = 35). As up to 25% of youth gender
      referrals have co-occurring autism, measure development included a well
      characterized supplementary sample of autistic transgender youth to maximize the
      applicability of the questionnaire. Following its development and refinement, the
      Transgender Youth Fertility Attitudes Questionnaire was pilot tested with
      transgender youth (nonautistic and autistic) and their parents (N = 51). RESULTS:
      The participatory process produced parallel child and parent questionnaires
      addressing fertility and FP knowledge and attitudes. In the pilot trial, youth
      and parents expressed generally similar attitudes about fertility and FP. Most
      youth (92%) reported learning about gender-affirming hormone therapy-related
      fertility issues online. Although many transgender youth endorsed a wish to
      parent children at some point, few (24%) expressed desire to have their own
      biological child. However, many youth wondered, or did not know, if their
      feelings about having a biological child might change in the future. CONCLUSIONS:
      This study presents a novel procedure for developing instruments for use with
      transgender youth. Although a majority of transgender youth in this study were
      uninterested in using FP, extending exploration of this topic with young people
      may be useful given findings of their openness to the idea that fertility
      attitudes may change in adulthood.

PMID- 29033161
TI  - Impact of a socio-educational intervention to improve the quality of life of
      patients with fibromyalgia: A quasi-experimental design.
AB  - OBJECTIVE: To evaluate the impact of a socio-educational intervention to improve
      the quality of life of patients with fibromyalgia. METHOD: Out of 132 eligible
      candidates, 128 patients participated with a diagnosis of fibromyalgia (ACR
      1990/2010), over 18 years of age, who did not have cognitive problems or mental
      disorders in acute phase and lived in the catchment area of the participating
      CAPs. The patients underwent intervention for 5 weeks to strengthen self
      management of pain and improve quality of life. Socio-demographic variables,
      satisfaction and quality of life (SF-36) were studied. Pre-post measurements were
      made on the 128 participants and follow-up at 2 months on 120 (8 did not agree to
      be contacted). RESULTS: Comparing the pre-post-intervention scores (non
      parametric Wilcoxon test), it was found that 71.09% reported a higher perception
      of quality of life in the Mental health domain and lower percentage of
      improvement (28.91%) in the Physical role domain. When comparing pre-post-follow
      up scores (Friedman's test), mean perception improved in all domains and remained
      at 2-month follow-up (P<.001). Finally, the average satisfaction with the
      intervention received was 90.55% (SD 9.86; min. 41, max. 100). CONCLUSIONS: When
      assessing the impact of the intervention, there was an improvement in the post
      and follow-up scores. This finding is largely due to the fact that the
      intervention strengthens the patient's self-mastery of their abilities to control
      pain and improve their perception of quality of life.

PMID- 29033162
TI  - Moving towards a nursing model to understand bereavement and loss.

PMID- 29033163
TI  - The first Italian heart transplantation: The history of the pioneers' experience.

PMID- 29033164
TI  - UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy.
AB  - Six UK studies investigating stereotactic ablative radiotherapy (SABR) are
      currently open. Many of these involve the treatment of oligometastatic disease at
      different locations in the body. Members of all the trial management groups
      collaborated to generate a consensus document on appropriate organ at risk dose
      constraints. Values from existing but older reviews were updated using data from
      current studies. It is hoped that this unified approach will facilitate
      standardised implementation of SABR across the UK and will allow meaningful
      toxicity comparisons between SABR studies and internationally.

PMID- 29033166
TI  - Early peripheral endothelial dysfunction predicts myocardial infarct extension
      and microvascular obstruction in patients with ST-elevation myocardial
      infarction.
AB  - INTRODUCTION AND OBJECTIVES: The role of endothelial dysfunction (ED) in patients
      with ST-elevation myocardial infarction (STEMI) is poorly understood. Peripheral
      arterial tonometry (PAT) allows non-invasive evaluation of ED, but has never been
      used for this purpose early after primary percutaneous coronary intervention (P
      PCI). Our purpose was to analyze the relation between ED assessed by PAT and both
      the presence of microvascular obstruction (MVO) and infarct extension in STEMI
      patients. METHODS: ED was assessed by the reactive hyperemia index (RHI),
      measured by PAT and defined as RHI <1.67. Infarct extension was assessed by
      troponin I (TnI) release and contrast-enhanced cardiac magnetic resonance
      (ceCMR). MVO was assessed by ceCMR and by indirect angiographic and ECG
      indicators. An echocardiogram was also performed in the first 12 h. RESULTS: We
      included 38 patients (mean age 60.0+/-13.7 years, 29 male). Mean RHI was 1.87+/
      0.60 and 16 patients (42.1%) had ED. Peak TnI (median 118 mg/dl, IQR 186 vs.
      67/81, p=0.024) and AUC of TnI (median 2305, IQR 2486 vs. 1076/1042, p=0.012)
      were significantly higher in patients with ED, who also showed a trend for more
      transmural infarcts (63.6% vs. 22.2%, p=0.06) and larger infarct mass on ceCMR
      (median 17.5%, IQR 15.4 vs. 10.1/10.3, p=0.08). Left ventricular ejection
      fraction (LVEF) was lower and wall motion score index (WMSI) was higher on both
      echocardiogram and ceCMR in patients with ED. On ceCMR, MVO was more frequent in
      patients with RHI <1.67 (54.5% vs. 11.1%, p=0.03). ECG and angiographic
      indicators of MVO all showed a trend toward worse results in these patients.
      CONCLUSIONS: The presence of ED assessed by PAT 24 h after P-PCI in patients with
      STEMI is associated with larger infarcts, lower LVEF, higher WMSI and higher
      prevalence of MVO.

PMID- 29033165
TI  - Molecular epidemiological study of familial amyotrophic lateral sclerosis in
      Japanese population by whole-exome sequencing and identification of novel HNRNPA1
      mutation.
AB  - To elucidate the genetic epidemiology of familial amyotrophic lateral sclerosis
      (FALS) in the Japanese population, we conducted whole-exome sequencing analysis
      of 30 FALS families in whom causative mutations have not been identified in
      previous studies. Consequently, whole-exome sequencing analysis revealed novel
      mutations in HNRNPA1, TBK1, and VCP. Taken together with our previous results of
      mutational analyses by direct nucleotide sequencing analysis, a microarray-based
      resequencing method, or repeat-primed PCR analysis, causative mutations were
      identified in 41 of the 68 families (60.3%) with SOD1 being the most frequent
      cause of FALS (39.7%). Of the mutations identified in this study, a novel
      c.862/1018C>G (p.P288A/340A) mutation in HNRNPA1 located in the nuclear
      localization signal domain of hnRNPA1, enhances the recruitment of mutant hnRNPA1
      into stress granules, indicating that an altered nuclear localization signal
      activity plays an essential role in amyotrophic lateral sclerosis pathogenesis.

PMID- 29033167
TI  - Spatial variability in the concentrations of metals in beached microplastics.
AB  - Heavy metals and microplastics have been considered as threats to the marine
      environment and the interactions between these two pollutants are poorly
      understood. This study investigates the interactions between metals adsorbed in
      pellets collected randomly from 19 beaches along the coast of Sao Paulo State in
      southeastern Brazil, comparing these levels with those in virgin pellets. The
      samples were analyzed for Al, Cr, Cu, Fe, Mn, Sn, Ti and Zn by inductively
      coupled plasma optical emission spectroscopy (ICP-OES). The polymers were
      solubilized via acid digestion. The highest levels occurred with Fe (227.78mgkg-1
      - Itaguare) and Al (45.27mgkg-1 - Guarau) in the same areas, which are closer to
      the Port of Santos. The metal adsorption on pellets collected is greater than
      that on virgin pellets. In this context, pellets can be considered to be a
      carrier for the transport of metals in the environment, even in small quantities.

PMID- 29033168
TI  - Rocky shoreline protocols miss microplastics in marine debris surveys (Fogo
      Island, Newfoundland and Labrador).
AB  - Most anthropogenic marine debris shoreline studies are conducted on sandy shores,
      rather than rocky coastlines. We amended a standardized protocol for monitoring
      marine debris on a high-loading beach composed of small rocks and cobbles in
      Newfoundland, Canada. Our protocol had two parts: we conducted stratified
      sampling to a depth of ~20cm below the surface of the rocks (standing survey),
      and surveyed accumulation of items on the surface of rocks every other day
      (loading survey). We found the vast majority of smaller items were below the
      surface. Only 17.2% of debris were microplastics (<5mm). Types of anthropogenic
      debris differed significantly between the standing survey and the loading survey.
      We found no relationship between either wind direction or wind speed, and
      distributions of debris. This study allows for a better understanding of marine
      debris detection along rocky coasts, and the limitations of protocols for
      studying them.

PMID- 29033169
TI  - Influence of the submarine volcanic eruption off El Hierro (Canary Islands) on
      the mesopelagic cephalopod's metal content.
AB  - This work investigates whether a submarine volcanic eruption off El Hierro
      (Canary Islands) in October 2011 influenced the metal contents of two deep water
      cephalopod species: Abraliopsis morisii and Pyroteuthis margaritifera. This was
      assessed by comparing metal contents in specimens collected off the island of El
      Hierro and in the neighbouring islands of La Palma and Tenerife during an
      experimental deep water fishing trip. The concentration of 20 heavy metals was
      analyzed in 180 specimens of A. morisii and P. margaritifera collected around the
      three islands to test for inter-island differences for each species and metal.
      While both species showed geographical differences in metal concentrations, the
      main finding was that A. morisii could be a bioindicator species for metals such
      as Li, Sr and Ca.

PMID- 29033170
TI  - Assessing the effect of mercury pollution on cultured benthic foraminifera
      community using morphological and eDNA metabarcoding approaches.
AB  - Mercury (Hg) is a highly toxic element for living organisms and is known to
      bioaccumulate and biomagnify. Here, we analyze the response of benthic
      foraminifera communities cultured in mesocosm and exposed to different
      concentrations of Hg. Standard morphological analyses and environmental DNA
      metabarcoding show evidence that Hg pollution has detrimental effects on benthic
      foraminifera. The molecular analysis provides a more complete view of
      foraminiferal communities including the soft-walled single-chambered
      monothalamiids and small-sized hard-shelled rotaliids and textulariids than the
      morphological one. Among these taxa that are typically overlooked in
      morphological studies we found potential bioindicators of Hg pollution. The
      mesocosm approach proves to be an effective method to study benthic foraminiferal
      responses to various types and concentrations of pollutants over time. This study
      further supports foraminiferal metabarcoding as a complementary and/or
      alternative method to standard biomonitoring program based on the morphological
      identification of species communities.

PMID- 29033171
TI  - PAH, PCB, TPH and mercury in surface sediments of the Delaware River Estuary and
      Delmarva Peninsula, USA.
AB  - Surface sediment concentrations of polycyclic aromatic hydrocarbons (PAH) and
      polychlorinated biphenyls (PCB), total petroleum hydrocarbons (TPH) and mercury,
      were compared from two areas with contrasting land use history, the industrial
      Delaware Estuary and the rural Delmarva Peninsula (USA). TPH in the Delaware (38
      616mg/kg) and saturate/aromatic fractions suggested petroleum/industrial sources
      compared to biogenic sources in the Delmarva coastal control (<34-159mg/kg).
      Within the Delaware the ?PAH18 ranged from 3749 to 22,324MUg/kg with isomeric
      ratios indicative of petroleum combustion source/s, conversely, those in the
      Delmarva (5-2139MUg/kg) also yielded relatively higher perylene that were
      consistent with natural background levels derived from vegetation/coal combustion
      source/s. ?PCB(tri-hepta) concentrations in the Delmarva (0.6-6.5MUg/kg) were
      less than the threshold effect concentration (TEC), whereas the Delaware had
      received much higher PCB loading (18.1-136.8MUg/kg) as evidenced by a
      significantly higher amounts in some samples (>TEC).

PMID- 29033172
TI  - Environmental characterization of a semiarid hyper saline system based on
      dissolved trace metal-macronutrient synergy: A multivariate spatio-temporal
      approach.
AB  - Trace metals and macronutrients play key roles in marine biogeochemical
      processes. Despite their higher availability, no reliable information is
      available on their ecological role in the hypersaline waters of NW Arabian Gulf.
      The present study identifies their synergistic effect on environmental
      characteristics and autotrophic biomass in the shallow coastal and offshore
      waters, off Kuwait on a seasonal basis. Surface water samples collected along
      four predefined transects were analyzed for physico-chemical and biological
      variables during summer (n=27) and winter (n=27) seasons. Multivariate analyses
      revealed clear spatial and seasonal trends, and identified the best suit of
      environmental variables responsible for the seasonal variability in phytoplankton
      biomass. Using statistically derived supply to demand ratios, carbon-trace metal
      stoichiometry, and bioavailability of trace metals, we propose possible growth
      regulating factors for phytoplankton on a seasonal basis in the NW Arabian Gulf,
      off Kuwait. This is the first report on trace metals from the entire Arabian
      Gulf, using clean techniques and multivariate statistical approach.

PMID- 29033174
TI  - Airborne particle-bound brominated flame retardants: Levels, size distribution
      and indoor-outdoor exchange.
AB  - The quality of indoor environments has a significant impact on public health.
      Usually, an indoor environment is treated as a static box, in which
      physicochemical reactions of indoor air contaminants are negligible. This results
      in conservative estimates for primary indoor air pollutant concentrations, while
      also ignoring secondary pollutants. Thus, understanding the relationship between
      indoor and outdoor particles and particle-bound pollutants is of great
      significance. For this reason, we collected simultaneous indoor and outdoor
      measurements of the size distribution of airborne brominated flame retardant
      (BFR) congeners. The time-dependent concentrations of indoor particles and
      particle-bound BFRs were then estimated with the mass balance model, accounting
      for the outdoor concentration, indoor source strength, infiltration, penetration,
      deposition and indoor resuspension. Based on qualitative observation, the size
      distributions of SigmaPBDE and SigmaHBCD were characterized by bimodal peaks.
      According to our results, particle-bound BDE209 and gamma-HBCD underwent
      degradation. Regardless of the surface adsorption capability of particles and the
      physicochemical properties of the target compounds, the concentration of BFRs in
      particles of different size fractions seemed to be governed by the particle
      distribution. Based on our estimations, for airborne particles and particle-bound
      BFRs, a window-open ventilated room only takes a quarter of the time to reach an
      equilibrium between the concentration of pollutants inside and outside compared
      to a closed room. Unfortunately, indoor pollutants and outdoor pollutants always
      exist simultaneously, which poses a window-open-or-closed dilemma to achieve
      proper ventilation.

PMID- 29033173
TI  - Source apportionment for fine particulate matter in a Chinese city using an
      improved gas-constrained method and comparison with multiple receptor models.
AB  - PM2.5 is one of the most studied atmospheric pollutants due to its adverse
      impacts on human health and welfare and the environment. An improved model (the
      chemical mass balance gas constraint-Iteration: CMBGC-Iteration) is proposed and
      applied to identify source categories and estimate source contributions of PM2.5.
      The CMBGC-Iteration model uses the ratio of gases to PM as constraints and
      considers the uncertainties of source profiles and receptor datasets, which is
      crucial information for source apportionment. To apply this model, samples of
      PM2.5 were collected at Tianjin, a megacity in northern China. The ambient PM2.5
      dataset, source information, and gas-to-particle ratios (such as SO2/PM2.5,
      CO/PM2.5, and NOx/PM2.5 ratios) were introduced into the CMBGC-Iteration to
      identify the potential sources and their contributions. Six source categories
      were identified by this model and the order based on their contributions to PM2.5
      was as follows: secondary sources (30%), crustal dust (25%), vehicle exhaust
      (16%), coal combustion (13%), SOC (7.6%), and cement dust (0.40%). In addition,
      the same dataset was also calculated by other receptor models (CMB, CMB
      Iteration, CMB-GC, PMF, WALSPMF, and NCAPCA), and the results obtained were
      compared. Ensemble-average source impacts were calculated based on the seven
      source apportionment results: contributions of secondary sources (28%), crustal
      dust (20%), coal combustion (18%), vehicle exhaust (17%), SOC (11%), and cement
      dust (1.3%). The similar results of CMBGC-Iteration and ensemble method indicated
      that CMBGC-Iteration can produce relatively appropriate results.

PMID- 29033175
TI  - Projecting temperature-related years of life lost under different climate change
      scenarios in one temperate megacity, China.
AB  - Temperature has been associated with population health, but few studies have
      projected the future temperature-related years of life lost attributable to
      climate change. To project future temperature-related disease burden in Tianjin,
      we selected years of life lost (YLL) as the dependent variable to explore YLL
      attributable to climate change. A generalized linear model (GLM) and distributed
      lag non-linear model were combined to assess the non-linear and delayed effects
      of temperature on the YLL of non-accidental mortality. Then, we calculated the
      YLL changes attributable to future climate scenarios in 2055 and 2090. The
      relationships of daily mean temperature with the YLL of non-accident mortality
      were basically U-shaped. Both the daily mean temperature increase on high
      temperature days and its drop on low-temperature days caused an increase of YLL
      and non-accidental deaths. The temperature-related YLL will worsen if future
      climate change exceeds 2  degrees C. In addition, the adverse effects of extreme
      temperature on YLL occurred more quickly than that of the overall temperature.
      The impact of low temperature was greater than that of high temperature. Men were
      vulnerable to high temperature compared with women. This analysis highlights that
      the government should formulate environmental policies to reach the Paris
      Agreement goal.

PMID- 29033176
TI  - Estimating spatiotemporal distribution of PM1 concentrations in China with
      satellite remote sensing, meteorology, and land use information.
AB  - BACKGROUND: PM1 might be more hazardous than PM2.5 (particulate matter with an
      aerodynamic diameter <= 1 MUm and <=2.5 MUm, respectively). However, studies on
      PM1 concentrations and its health effects are limited due to a lack of PM1
      monitoring data. OBJECTIVES: To estimate spatial and temporal variations of PM1
      concentrations in China during 2005-2014 using satellite remote sensing,
      meteorology, and land use information. METHODS: Two types of Moderate Resolution
      Imaging Spectroradiometer (MODIS) Collection 6 aerosol optical depth (AOD) data,
      Dark Target (DT) and Deep Blue (DB), were combined. Generalised additive model
      (GAM) was developed to link ground-monitored PM1 data with AOD data and other
      spatial and temporal predictors (e.g., urban cover, forest cover and calendar
      month). A 10-fold cross-validation was performed to assess the predictive
      ability. RESULTS: The results of 10-fold cross-validation showed R2 and Root Mean
      Squared Error (RMSE) for monthly prediction were 71% and 13.0 MUg/m3,
      respectively. For seasonal prediction, the R2 and RMSE were 77% and 11.4 MUg/m3,
      respectively. The predicted annual mean concentration of PM1 across China was
      26.9 MUg/m3. The PM1 level was highest in winter while lowest in summer.
      Generally, the PM1 levels in entire China did not substantially change during the
      past decade. Regarding local heavy polluted regions, PM1 levels increased
      substantially in the South-Western Hebei and Beijing-Tianjin region. CONCLUSIONS:
      GAM with satellite-retrieved AOD, meteorology, and land use information has high
      predictive ability to estimate ground-level PM1. Ambient PM1 reached high levels
      in China during the past decade. The estimated results can be applied to evaluate
      the health effects of PM1.

PMID- 29033177
TI  - Arsenic-phosphorus interactions in the soil-plant-microbe system: Dynamics of
      uptake, suppression and toxicity to plants.
AB  - High arsenic (As) concentrations in the soil, water and plant systems can pose a
      direct health risk to humans and ecosystems. Phosphate (Pi) ions strongly
      influence As availability in soil, its uptake and toxicity to plants. Better
      understanding of As(V)-Pi interactions in soils and plants will facilitate a
      potential remediation strategy for As contaminated soils, reducing As uptake by
      crop plants and toxicity to human populations via manipulation of soil Pi
      content. However, the As(V)-Pi interactions in soil-plant systems are complex,
      leading to contradictory findings among different studies. Therefore, this review
      investigates the role of soil type, soil properties, minerals, Pi levels in soil
      and plant, Pi transporters, mycorrhizal association and microbial activities on
      As-Pi interactions in soils and hydroponics, and uptake by plants, elucidate the
      key mechanisms, identify key knowledge gaps and recommend new research
      directions. Although Pi suppresses As uptake by plants in hydroponic systems, in
      soils it could either increase or decrease As availability and toxicity to plants
      depending on the soil types, properties and charge characteristics. In soil,
      As(V) availability is typically increased by the addition of Pi. At the root
      surface, the Pi transport system has high affinity for Pi over As(V). However, Pi
      concentration in plant influences the As transport from roots to shoots.
      Mycorrhizal association may reduce As uptake via a physiological shift to the
      mycorrhizal uptake pathway, which has a greater affinity for Pi over As(V) than
      the root epidermal uptake pathway.

PMID- 29033178
TI  - Predictors of thallium exposure and its relation with preterm birth.
AB  - Thallium (Tl) is a well-recognized hazardous toxic heavy metal that has been
      reported to have embryotoxicity and fetotoxicity. However, little is known about
      its association with preterm birth (PTB) in humans. We aimed to evaluate the
      predictors of Tl exposure and assessed its relation with PTB. The study
      population included 7173 mother-infant pairs from a birth cohort in Wuhan, China.
      Predictors of Tl concentrations were explored using linear regression analyses,
      and associations of Tl exposure with risk of PTB or gestational age at birth were
      estimated using logistic regression or generalized linear models. The geometric
      mean and median values of urinary Tl concentrations were 0.28 MUg/L (0.55 MUg/g
      creatinine) and 0.29 MUg/L (0.53 MUg/g creatinine). We found that maternal
      urinary Tl concentrations varied by gestational weight gain, educational
      attainment, multivitamin and iron supplementations. Women with Tl concentrations
      higher than 0.80 MUg/g creatinine were at higher risk of giving birth prematurely
      versus those with Tl concentrations lower than 0.36 MUg/g creatinine [adjusted
      odds ratio (95% confidence interval (CI)): 1.55 (1.05, 2.27)], and the
      association was more pronounced in PTB with premature rupture of membranes (PROM)
      rather than in PTB without PROM. About 3-fold increase in creatinine-corrected Tl
      concentrations were associated with 0.99-day decrease in gestational length (95%
      CI: -1.36, -0.63). This is the first report on the associations between maternal
      Tl exposure and the risk of PTB.

PMID- 29033179
TI  - Editorial Commentary: The optimistic future of remote hemodynamic monitoring.

PMID- 29033180
TI  - Advanced Thoracoscopy: What Is the Critical Information in Case Reports and How
      Do We Achieve the Next Level?

PMID- 29033181
TI  - Pathobiology of HER 2 positive small invasive (T1a,b) breast cancer: "A wolf in
      sheep's clothing".
AB  - Small invasive breast cancers (cancers with maximum diameter <1cm, T1a,b) become
      more prevalent form of breast cancer as a result of the introduction of breast
      cancer mammographic screening programs. Although associated with an excellent
      prognosis, T1a,b breast cancers are heterogeneous group of tumors with
      prognostically unfavorable subset of cases, primarily those with axillary lymph
      node metastases. To determine if the HER2 overexpression is associated with the
      prognostically unfavorable traditional clinicopathological features in this group
      of breast cancers, clinicopathological features (age, tumor size, histological
      type, histological grade, nodal status, hormone receptor status, proliferation
      index, lymphovascular invasion, ploidy) of 38 HER2 positive T1a,b cancers were
      compared with those of the control group consisting of 315 HER2 negative T1a,b
      cancers. The comparison of clinicopathological features was made using chi2 and t
      test. HER2 positive T1a,b breast cancers were significantly associated with
      higher tumor grades (p<0.001), negative hormone receptors (p=0.008), presence of
      lymphovascular invasion (p=0.025), high proliferation index (p<0.001), and
      abnormal DNA content (p=0.04). We also noticed the higher frequency of lymph node
      positive cases in the HER2 positive group of cancers (p=0.05). There were no
      differences in age, tumor size and histological type between investigated groups.
      Our group of HER2 positive T1a,b breast cancers was associated with many
      unfavorable traditional prognostic factors, demonstrating that this subtype of
      early breast cancer has an aggressive biological phenotype which may have
      potential benefit from adjuvant chemo and immunotherapy.

PMID- 29033182
TI  - PD-L1 expression in HNPCC-associated colorectal cancer.
AB  - BACKGROUND: PD-L1 immunohistochemistry is predictive for molecular inhibitors of
      PD-1/PD-L1 immune checkpoint. Therefore, this study evaluated the PD-L1
      expression in patients with Hereditary Non-Polyposis Colorectal Cancer (HNPCC).
      METHODS: Immunohistochemical expression of PD-L1 in carcinoma cells, stromal
      macrophages and lymphocytes of 40 HNPCC-patients with colorectal cancer was
      scored semi-quantitatively. RESULTS: Focal (2 cases) to extensive (2 cases) PD-L1
      immunopositivity of carcinoma cells was detected in 4 out of 40 cases (10.0%).
      Stromal macrophages were immunopositive in 28 out of 40 cases (70.0%).
      Lymphocytes showed PD-L1 expression in 3 out of 40 cases (7.5%). Simultaneous
      immunopositivity of stromal macrophages and tumor cells was detected in two
      MLH1/PMS2-deficient and two MSH2/MSH6-deficient cases. CONCLUSION: A subset of
      HNPCC-associated colorectal cancers in this study clearly showed PD-L1 expression
      of tumor epithelia and immune cells, therefore, the detection of PD-L1 status is
      useful.

PMID- 29033183
TI  - The overexpression and predictive significance of MMP-12 in esophageal squamous
      cell carcinoma.
AB  - Matrix metalloproteinase (MMP)-mediated degradation of the extracellular matrix
      is a major factor for tumor invasion and metastasis. MMP-12, as metalloelastase,
      its function in tumor progression remains contradictory. This study was
      undertaken to investigate the role of MMP-12 in esophageal squamous cell
      carcinoma (ESCC). We analyzed the protein expression of MMP-12 and its
      association with clinicopatholigical parameters, as well as survival analysis.
      MMP-12 was highly expressed in tumor cells comparing with normal epithelial
      cells. The high expression of MMP-12 was significantly correlated with tumor
      grade and stage, nodal metastasis and poor survival of ESCC. Cox multivariate
      analysis revealed that MMP-12 was an independent prognostic factor in ESCC. Our
      results suggest that MMP-12 might act as a potential target for the development
      of novel therapeutics of esophageal squamous cell carcinoma.

PMID- 29033184
TI  - Over expression of HIF1alpha is associated with inactivation of both LimD1 and
      VHL in renal cell carcinoma: Clinical importance.
AB  - It is evident that the association of LimD1 and VHL could regulate stabilization
      of HIF1alpha protein. In this study, the expression of LimD1, VHL and HIF1alpha
      was analyzed in primary renal cell carcinoma (RCC) samples to understand their
      association with development of the disease. For this purpose,
      immunohistochemical expression analysis of LimD1, VHL and HIF1alpha was performed
      along with proliferation marker PCNA in 32 primary RCC samples in different
      subtypes at different clinical stages of Indian patients (year: 2014-2016).
      Significant decrease (P<0.05) in LimD1 and VHL expression was observed in
      different subtypes of RCC and in early invasive lesions. High nuclear expression
      of HIF1alpha was seen in different subtypes as well as in early invasive lesions.
      The LimD1 and VHL expression strongly correlated with each other, while inversely
      correlated with HIF1alpha. On the other hand, increased expression of PCNA was
      seen in different sub types and in early invasive lesions. The PCNA expression
      was negatively correlated with LimD1 and VHL expression and positively correlated
      with HIF1alpha. Thus, our data indicates that the reduced expression of LimD1 and
      VHL might have synergistic effect on induction of HIF1alpha resulting increased
      cellular proliferation and progression of the disease.

PMID- 29033185
TI  - The expression level of miR-203 in patients with gastric cancer and its clinical
      significance.
AB  - BACKGROUND: The clinical significance of miR-203 and its prognostic value have
      not been investigated in gastric cancer. METHODS: We assessed miR-203 expression
      in 141 gastric cancer samples and 141 paired non-cancerous samples by real-time
      PCR and calculated using the 2-DeltaDeltaCt method. Differences between groups
      were examined for statistical significance by Student's t-test. Survival curves
      were computed by the Kaplan-Meier method, and differences between survival curves
      were compared by the log rank test. RESULTS: The expression of miR-203 was
      significantly lower in gastric cancer samples compared to non-cancerous samples
      (P<0.0001). Low miR-203 expression was found to be closely correlated with
      advanced stage (p=0.005), and lymph node involvement (p=0.009). Kaplan-Meier
      analysis with the log-rank test indicated that low miR-203 expression had a
      significant impact on overall survival (39.4% vs. 62.5%; P=0.043) and progression
      free survival (32.5% vs. 58.6%; P=0.023). Furthermore, multivariate analysis
      revealed that miR-203 expression level was independent prognostic factors for
      overall survival (HR=2.73, 95% CI: 1.69-8.91; P=0.01), as well as progression
      free survival (HR=4.19, 95% CI: 2.91-10.12; P=0.005). CONCLUSION: Our data
      validate an important clinical significance of miR-203 in gastric cancer, and
      reveal that it might be a potential prognostic factor for gastric cancer. Large-
      scale and long-term follow-up studies are needed to confirm the significance of
      miR-203 in gastric cancer.

PMID- 29033186
TI  - A preliminary study on fetal lung injury in a rat model of acute pancreatitis in
      pregnancy.
AB  - Acute pancreatitis in pregnancy (APIP), which was thought to be rare, is becoming
      more frequent. In addition, high perinatal mortality among fetuses has been
      reported. Our research aimed to investigate and assess fetal lung injury in a rat
      model of APIP and its possible mechanisms. The APIP model was induced by sodium
      taurocholate in Sprague-Dawley rats during the third trimester. Sham-operated
      (SO) rats in late gestation were used as controls, and dynamic observation and
      detection in the SO and acute pancreatitis (AP) groups were performed at 3 time
      points. Histological changes in the fetal lungs, as well as the maternal pancreas
      and placenta were assessed. The levels of serum amylase, lipase, TNF-alpha and IL
      1beta were detected in maternal rats, and the expression of surfactant proteins
      A, B, C and D as well as their mRNA were determined. In this study, fetal lung
      injury as well as maternal pancreas and placenta injuries occurred in a time
      dependent manner. The levels of serum amylase, lipase and TNF-alpha were markedly
      increased in maternal rats, and the levels of surfactant proteins A, B, C and D
      in fetal lungs were significantly decreased in the fetal lungs of the AP group.
      Ultrastructure injuries and the dysregulated synthesis and secretion of pulmonary
      surfactant proteins were observed in the AP group. Our research suggests that
      fetal lung injury is involved in the rat model of APIP and that the dysregulated
      synthesis and secretion of pulmonary surfactant proteins play a critical role in
      fetal lung injury during APIP.

PMID- 29033187
TI  - A TERT-CLPTM1 locus polymorphism (rs401681) is associated with EGFR mutation in
      non-small cell lung cancer.
AB  - Telomere length is associated with lung carcinogenesis, and recent studies have
      focused on telomere-maintaining genes and their polymorphisms. Cancer
      susceptibility of the rs401681 polymorphism, located in the TERT-CLPTM1L locus,
      has been studied in many cancers. We examined the clinicopathological and
      prognostic value of rs401681 variants in lung cancer. The relationship between
      rs401681 variants and telomere length was analyzed in 134 non-small cell lung
      cancers (NSCLCs). The rs401681 polymorphism had the following genotype
      frequencies: C/C in 52.2% of the samples, C/T in 30.6%, and T/T in 17.2%. The T
      allele showed a strong correlation with EGFR mutation (p=0.037). Telomeres in the
      tumor samples were 3.26-fold longer, on average, than telomeres in matched normal
      samples (SD=0.48), and there were no differences in telomere length according to
      rs401681 polymorphism. Smoking was associated with telomere shortening (p=0.01).
      Survival analysis showed no prognostic value for rs401681 polymorphisms or
      telomere length in NSCLC. These results suggested that the rs401681 polymorphism
      contributes to lung carcinogenesis only in patients harboring an EGFR mutation.
      However, the polymorphism was not associated with survival; therefore, further
      comprehensive analysis should be performed.

PMID- 29033188
TI  - PPP1CC is associated with astrocyte and microglia proliferation after traumatic
      spinal cord injury in rats.
AB  - Reactive astrogliosis and microgliosis after spinal cord injury (SCI) contribute
      to glial scar formation that impedes axonal regeneration. The mechanisms
      underlying reactive astrocyte and microglia proliferation upon injury remain
      partially understood. Protein phosphatase 1, catalytic subunit, gamma isozyme
      (PPP1CC) participates in cell proliferation, differentiation and apoptosis.
      However, the expression and functions of PPP1CC following SCI are still unknown.
      In this study, an acute spinal cord contusion injury model in adult rats was
      established to investigate the potential role of PPP1CC during the pathological
      process of SCI. The palpable expression increase of PPP1CC after SCI was found by
      western blot and immunohistochemistry staining. Double immunofluorescence
      staining showed that PPP1CC expression mainly increased in astrocytes and
      microglia, as well as PPP1CC and proliferating cell nuclear antigen (PCNA) co
      localized in astrocytes and microglia. Furthermore, PCNA expression also elevated
      after SCI in a similar manner as PPP1CC. In vitro, PPP1CC and PCNA expression in
      primary rat spinal cord astrocytes and microglia changed in a similar
      concentration- and time-dependent manner according to LPS treatment. In addition,
      PPP1CC knockdown in astrocytes and microglia resulted in the decrease of PCNA
      expression and the number of Brdu positive cells after LPS stimulation, showing
      that PPP1CC promoted astrocyte and microglia proliferation after inflammation. In
      a word, PPP1CC might be associated with astrocyte and microglia proliferation
      after SCI, implying that PPP1CC is a potential molecular target for the therapy
      of SCI.

PMID- 29033189
TI  - MiR-375: A prospective regulator in medullary thyroid cancer based on microarray
      data and bioinformatics analyses.
AB  - BACKGROUND: This research aims to investigate the prospective molecular mechanism
      of miR-375 in Medullary Thyroid Cancer (MTC). MATERIAL AND METHODS: The
      expression level of miR-375 in MTC was explored with microarray data from Gene
      Expression Omnibus (GEO). To gather the putative target genes of miR-375, we
      selected eligible datasets in GEO, in which antagomir-375 and premir-375 were
      transfected to provide the miR-375-related genes. Subsequently, we attained the
      intersection of the results of GEO microarray data and 12 online target genes
      prediction database as the prospective target genes. Furthermore, we conducted in
      silico analysis including gene ontology (GO) enrichment analysis, Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathways annotations and Protein-Protein
      Interactions (PPI) analysis to provide an overview of the function of miR-375 in
      MTC. Finally, data from The Cancer Genome Atlas (TCGA) and The Human Protein
      Atlas (THPA) were used for a validation. RESULTS: Up-regulation could be
      confirmed with the data from GSE40807. GEO dataset GSE67742 provided 10,596 miR
      375-related genes, while 12 online prediction databases showed that 3352 target
      genes appeared no less than four times. Finally, the intersection of the two
      groups of genes included 1132 prospective targets. In aspect of functional
      annotation, negative regulation of transcription from RNA polymerase II promoter
      (P=9.83E-06), golgi membrane (P=9.98E-05) and pathway of protein binding (P=3.63E
      07) were highlighted as the most enriched terms with GO analysis. With regards to
      PPI network, 162 hub genes that interacted with no less than 10 other different
      genes was visualized, among which PI3K/Akt signaling pathway was the most
      enriched pathway as assessed by KEGG. Furthermore, two genes (JAK2 and NGFR) in
      PI3K/Akt signaling pathway showed down-regulated patterns in both mRNA and
      protein levels. CONCLUSION: The higher expression level of miR-375 might play a
      pivotal role in the tumorigenesis of MTC via targeting multiple key pathways,
      especially PI3K/Akt pathway. However, the exact molecular mechanism of miR-375
      needs to be verified with in-depth investigation in the future.

PMID- 29033190
TI  - 3D modelling of radical prostatectomy specimens: Developing a method to quantify
      tumor morphometry for prostate cancer risk prediction.
AB  - Prostate cancer displays a wide spectrum of clinical behaviour from biological
      indolence to rapidly lethal disease, but we remain unable to accurately predict
      an individual tumor's future clinical course at an early curable stage. Beyond
      basic dimensions and volume calculations, tumor morphometry is an area that has
      received little attention, as it requires the analysis of the prostate gland and
      tumor foci in three-dimensions. Previous efforts to generate three-dimensional
      prostate models have required specialised graphics units and focused on the
      spatial distribution of tumors for optimisation of biopsy strategies rather than
      to generate novel morphometric variables such as tumor surface area. Here, we
      aimed to develop a method of creating three-dimensional models of a prostate's
      pathological state post radical prostatectomy that allowed the derivation of
      surface areas and volumes of both prostate and tumors, to assess the method's
      accuracy to known clinical data, and to perform initial investigation into the
      utility of morphometric variables in prostate cancer prognostication. Serial
      histology slides from 21 prostatectomy specimens covering a range of tumor sizes
      and pathologies were digitised. Computer generated three-dimensional models of
      tumor and prostate space filling models were reconstructed from these scanned
      images using Rhinoceros 4.0 spatial reconstruction software. Analysis of three
      dimensional modelled prostate volume correlated only moderately with weak
      concordance to that from the clinical data (r=0.552, theta=0.405), but tumor
      volume correlated well with strong concordance (r=0.949, theta=0.876). We divided
      the cohort of 21 patients into those with features of aggressive tumor versus
      those without and found that larger tumor surface area (32.7 vs 3.4cc, p=0.008)
      and a lower tumor surface area to volume ratio (4.7 vs 15.4, p=0.008) were
      associated with aggressive tumor biology.

PMID- 29033191
TI  - Effect of the ultraviolet light treatment and storage methods on the biological
      activity of a titanium implant surface.
AB  - OBJECTIVE: We evaluated whether the biological activity of the surface of
      titanium, when stored in an aqueous solution, in low vacuum, and under ambient
      conditions after ultraviolet light (UV) treatment is comparable to that of the
      surface immediately after UV treatment for 15min and that after dielectric
      barrier discharge (DBD) plasma treatment for 15min. METHODS: Grade IV titanium
      discs with machined surfaces were irradiated with UV and their surface properties
      were evaluated immediately and after storage for 28days in distilled H2O (dH2O),
      a vacuum desiccator (31.325kPa), and a sealed container under air. Their surface
      characteristics were evaluated by atomic force microscopy, X-ray diffraction,
      contact angle analysis, and X-ray photoelectron spectroscopy. Biological
      activities were determined by analyzing the albumin adsorption, MC3T3-E1 cell
      adhesion, and cytoskeleton development. RESULTS: Hydrophilicity of titanium
      surfaces stored in dH2O was comparable to that immediately after UV treatment and
      higher than that immediately after DBD plasma treatment (P<0.001). Storage in
      dH2O and in low vacuum immediately after UV treatment prevented hydrocarbon
      contamination and maintained elevated amounts of titanium and oxygen. After 28
      days, protein adsorption, cellular adhesion, and cytoskeletal development of
      MC3T3-E1 cells on the titanium surfaces stored in dH2O were significantly
      enhanced compared to those stored in low vacuum and under ambient conditions
      while being comparable to those immediately after UV and DBD plasma treatments.
      SIGNIFICANCE: UV treatment of the titanium implants followed by wet storage is
      useful for maintaining enhanced biological activity and overcoming biological
      aging during shelf storage.

PMID- 29033193
TI  - Cardiovascular risk assessment in elderly adults using SCORE OP model in a Latin
      American population: The experience from Ecuador.
AB  - INTRODUCTION AND OBJECTIVE: Cardiovascular disease (CVD) mortality is predicted
      to increase in Latin America countries due to their rapidly aging population.
      However, there is very little information about CVD risk assessment as a primary
      preventive measure in this high-risk population. MATERIAL AND METHODS: We
      predicted the national risk of developing CVD in Ecuadorian elderly population
      using the Systematic COronary Risk Evaluation in Older Persons (SCORE OP) High
      and Low models by risk categories/CVD risk region in 2009. Data on national
      cardiovascular risk factors were obtained from the Encuesta sobre Salud,
      Bienestar y Envejecimiento. We computed the predicted 5-year risk of CVD risk and
      compared the extent of agreement and reclassification in stratifying high-risk
      individuals between SCORE OP High and Low models. Analyses were done by risk
      categories, CVD risk region, and sex. RESULTS: In 2009, based on SCORE OP Low
      model almost 42% of elderly adults living in Ecuador were at high risk of
      suffering CVD over a 5-year period. The extent of agreement between SCORE OP High
      and Low risk prediction models was moderate (Cohen's kappa test of 0.5), 34% of
      individuals approximately were reclassified into different risk categories and a
      third of the population would benefit from a pharmacologic intervention to reduce
      the CVD risk. CONCLUSIONS: Forty-two percent of elderly Ecuadorians were at high
      risk of suffering CVD over a 5-year period, indicating an urgent need to tailor
      primary preventive measures for this vulnerable and high-risk population.

PMID- 29033192
TI  - Chemical affinity of 10-methacryloyloxydecyl dihydrogen phosphate to dental
      zirconia: Effects of molecular structure and solvents.
AB  - OBJECTIVES: To examine whether solvents and changing the molecular structure of
      10-Methacryloyloxydecyl dihydrogen phosphate (10-MDP) affect its chemical
      affinity to Yttria-stabilized tetragonal zirconia polycrystals (Y-TZP). METHODS:
      The present work investigated the chemical affinity between Y-TZP and 10-MDP
      dissolved in different solvents (acetone/ethanol/water or mixture) using X-ray
      photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and
      thermodynamic calculations. Shear bond strength (SBS) tests were used to evaluate
      the influence of different solvents on 10-MDP bonding. In addition, several
      phosphate ester monomer variants were created by changing the 10-MDP molecular
      structure. Changes included extending/shortening the spacer chain-length, and
      installing hydroxyl or carboxyl groups as side chains at different positions
      along the spacer chain. The thermodynamic parameters of the complexes formed
      between the 10-MDP variants and tetragonal zirconia were evaluated. RESULTS: The
      acquired data indicated that solvent is necessary for the formation of Zr-O-P
      bonds between 10-MDP and Y-TZP. Solvents affected the chemical affinity of 10-MDP
      to Y-TZP; acetone facilitated the best bonding, followed by ethanol. Changing the
      molecular structure of 10-MDP affected its chemical affinity to Y-TZP. The
      variants 15-MPDP, 12-MDDP, 6-hydroxyl-10-MDP and 6-carboxy-10-MDP all exhibited
      higher thermodynamic stability than 10-MDP when coordinated with tetragonal
      zirconia. In contrast, 2-MEP, 5-MPP, 10-hydroxyl-MDP, 10-carboxy-MDP, 5,6
      dihydroxyl-10-MDP and 5,6-dicarboxy-10-MDP exhibited lower thermodynamic
      stability. SIGNIFICANCE: 10-MDP coordinates with zirconia through dissociating in
      solvents. Changing the molecular structure of 10-MDP theoretically affects its
      chemical affinity to Y-TZP.

PMID- 29033194
TI  - Association of -319 C/T and +49 A/G polymorphisms of CTLA-4 gene in patients with
      hepatitis C virus infection.
AB  - INTRODUCTION AND OBJECTIVE: Molecular changes in the CTLA-4 gene can modify the
      ability to control T lymphocyte proliferation, and promote the persistence or
      elimination of the hepatitis C virus (HCV). We aimed to investigate the frequency
      and association of -319 C/T and +49 A/G polymorphism in the CTLA-4 gene in
      patients infected with HCV. METHODS: The CTLA-4 gene polymorphisms (-319 C/T in
      the promoter region, and +49 A/G in exon 1) were analysed by T-ARMS-PCR in 420
      individuals, including 205 chronic HCV infected patients and 215 healthy
      subjects. RESULTS: We found a positive association of +49G allele with HCV
      infection (OR 1.48; 95% CI 1.09-2.02; p=.02), and with males (OR 1.80; 95% CI
      1.16-2.79; p=.02), both in chronic disease (without cirrhosis). Also, significant
      differences in +49 A/G genotypes distribution between HCV infected patients and
      healthy subjects were shown in a dominant genetic model (GG+GA versus AA; OR
      1.57; 95% CI 1.05-2.33; p=.04). No significant differences were observed in the 
      319 C/T polymorphism between HCV infected patients and healthy subjects.
      Moreover, -319C/+49G haplotype confers susceptibility to HCV genotype 3 infection
      (OR 10.68; 95% CI 1.17-96.97; p=.04). CONCLUSIONS: The +49G allele confers
      susceptibility to HCV infection and with male gender, both in chronic disease. In
      addition, the -319C/+49G haplotype confers susceptibility to HCV genotype 3
      infection. Our results support an important role of the -319 C/T and +49 A/G
      polymorphisms in HCV infection.

PMID- 29033196
TI  - First-line obinutuzumab for follicular lymphoma.

PMID- 29033195
TI  - National Surgical Quality Improvement Program surgical risk calculator poorly
      predicts complications in patients undergoing radical cystectomy with urinary
      diversion.
AB  - PURPOSE: To evaluate the accuracy of the American College of Surgeons National
      Surgical Quality Improvement Programs (ACS-NSQIP) surgical risk calculator in
      patients undergoing radical cystectomy (RC) with urinary diversion. MATERIALS AND
      METHODS: Preoperative characteristics of patients who underwent RC with ileal
      conduit or orthotropic neobladder (ONB) between 2007 and 2016 were entered into
      the proprietary online ACS-NSQIP calculator to generate 30-day predicted risk
      profiles. Predicted and observed outcomes were compared by measuring Brier score
      (BS) and area under the receiver operating characteristic curve (AUC). RESULTS:
      Of 954 patients undergoing RC, 609 (64%) received ileal conduit and 345 (36%)
      received ONB. The calculator underestimated most risks by 10%-81%. The BSs
      exceeded the acceptable threshold of 0.01 and AUC were less than 0.8 for all
      outcomes in the overall cohort. The mean (standard deviation) predicted vs.
      observed length of stay was 9 (1.5) vs. 10.6 (7.4) days (Pearson's r = 0.09).
      Among patients who received ONB, adequate BS (<0.01) was observed for pneumonia,
      cardiac complications, and death. The receiver operating characteristic curve
      analysis revealed moderate accuracy of calculator for cardiac complications (AUC
      = 0.69) and discharge to rehab center (AUC = 0.75) among patients who underwent
      RC with ONB. CONCLUSIONS: The universal ACS-NSQIP calculator poorly predicts most
      postoperative complications among patients undergoing RC with urinary diversion.
      A procedure-specific risk calculator is required to better counsel patients in
      the preoperative setting and generate realistic quality measures.

PMID- 29033197
TI  - Oncolytic virus therapy in advanced melanoma.

PMID- 29033198
TI  - Copanlisib in heavily pretreated indolent lymphoma.

PMID- 29033199
TI  - Biomechanical characteristics of subscapularis-sparing approach for anatomic
      total shoulder arthroplasty.
AB  - BACKGROUND: A technique for retaining the superior 50% of the subscapularis
      insertion for anatomic total shoulder arthroplasty has been described. This
      cadaveric study biomechanically evaluates this subscapularis-sparing approach and
      compares it with a complete subscapularis release and repair technique to
      determine whether there is a higher load to failure. MATERIALS AND METHODS:
      Twelve matched pairs of human cadaveric arms were distributed into 3 test groups.
      Group 1 consisted of specimens with and without a 100% subscapularis release.
      Group 2 consisted of specimens with and without an inferior 50% subscapularis
      release. Group 3 consisted of specimens with either an inferior 50% or 100%
      release of the subscapularis footprint and repair. All tendon repairs were
      performed using bone tunnels and sutures. Specimens were biomechanically tested
      using non-destructive cyclic and tensile failure-inducing loads. RESULTS: In
      matched pairs, the following comparative results were obtained: native intact
      subscapularis specimens exhibited a load to failure of 1341.20 +/- 380.10 N
      compared with 380.10 +/- 138.79 N in the 100% release specimens (P = .029),
      native intact subscapularis specimens exhibited a load to failure of 1209.74 +/-
      342.18 N compared with 744.33 +/- 211.77 N in the 50% release specimens (P =
      .057), and 50% release and repair specimens exhibited a load to failure of 704.62
      +/- 165.53 N compared with 305.52 +/- 91.39 N in the 100% release and repair
      group (P = .029). CONCLUSION: Preservation of the superior 50% of the
      subscapularis demonstrates a higher load to failure compared with complete
      subscapularis release and repair using bone tunnels.

PMID- 29033200
TI  - Validation of a Spanish version of the EuroPrevall Food Allergy Quality of Life
      Questionnaire-Parental Form.
AB  - BACKGROUND: Food allergy can have a major impact on quality of life of children
      and their parents. Questionnaires have been developed to measure the impact of
      this disorder. We aimed to validate the EuroPrevall questionnaire on Food Allergy
      Quality of Life Questionnaire, Parent Form (FAQLQ-PF) and the Food Allergy
      Independent Measure (FAIM), translated into Spanish. METHODS: The internal
      consistency of the FAQLQ-PF and the FAIM, translated into Spanish (Spain) and
      completed by the parents of 74 children with IgE-mediated food allergy, were
      evaluated with Cronbach's alpha. To test construct validity of the FAQLQ-PF, its
      correlation with the FAIM was also calculated. To assess their discriminant
      validity, we compared the values of both depending on the number of offending
      foods and for children with and without anaphylaxis. RESULTS: The values of
      Cronbach's alpha for the three domains in the FAQLQ-PF were over 0.9. The value
      of alpha for FAIM questions was below 0.6, which was attributed to the wording of
      one question. When this question was removed, alpha increased to over 0.70. There
      was a significant correlation between the FAQLQ-PF score and the FAIM. There were
      significantly poorer FAQLQ-PF scores in children with more food allergies and
      worse FAIM in those who had had anaphylaxis. CONCLUSIONS: The Spanish version of
      the FAQLQ-PF had a good internal consistency, good construct validity and
      validity to discriminate patients with more food allergies and anaphylaxis. It
      can be used as a tool to evaluate and monitor the quality of life in families
      with food allergic children.

PMID- 29033201
TI  - Towards a Common Toolbox for Rarity: A Response to Violle et al.

PMID- 29033202
TI  - [Pyopneumothorax in rheumatoid arthritis].
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease
      affecting the joints but which frequently includes extra articular effects,
      including pulmonary nodules, which grow faster under immunosuppressive treatment.
      CASE REPORT: A 74 years old man, with mild asbestosis, underwent treatment with
      methotrexate then leflunomide (LEF) for seropositive RA. In February 2014, during
      monitoring of his asbestosis, chest CT scan showed the appearance of thick-walled
      cavitating lung nodules, with a central and sub pleural distribution. The patient
      was asymptomatic. Bronchoalveolar lavage excluded infection and tumor. LEF was
      stopped but in May 2014, the patient was admitted with respiratory infection and
      a pyopneumothorax which required surgical management. The postoperative course
      was complicated with a persistent pneumothorax. CONCLUSIONS: We describe a case
      of RA complicated by a pyopneumothorax after treatment with LEF. The risk of this
      complication could be reduced by regular chest imaging.

PMID- 29033203
TI  - [Reproducibility of strength and endurance measurements of the quadriceps in
      patients with COPD].
AB  - INTRODUCTION: Patients with COPD frequently have lower strength and endurance in
      their lower limbs compared to healthy subjects and evaluation of their quadriceps
      strength is recommended in practice. The handheld dynamometer has been validated
      and is easy to use for this measurement but its reproducibility has never been
      studied for endurance evaluation and only poorly for strength. The objective of
      this study was to estimate the inter and intra-operator reproducibility of
      maximal voluntary strength and endurance measurements of the quadriceps with a
      handheld dynamometer in patients with COPD. METHODS: The measurements of maximal
      voluntary strength and endurance were performed with a single handheld
      dynamometer using isometric contraction. Three measurement sessions were
      undertaken, separated by 24hours. The intra- and interoperator reproducibility
      were estimated by calculation of the intraclass correlation coefficient. RESULTS:
      Overall, 21 patients were included in the study. The intraclass correlation
      coefficient calculated for the maximal voluntary strength for intra and
      interoperator reliability ranged between 0.95 and 0.99. For endurance, the
      coefficient for intra-operator reliability was 0.81 and the two for interoperator
      reliability were 0.69 and 0.77. CONCLUSION: The handheld dynamometer allows an
      excellent inter and intra-operator reproducibility for the measurement of
      quadricipital maximal voluntary strength and a correct to excellent
      reproducibility for the measurement of quadricipital endurance. This tool may be
      used for the evaluation of quadriceps strength in clinical practice in COPD
      patients, particularly during rehabilitation.

PMID- 29033204
TI  - [Structuring the French thoracic oncology over the last 20 years].

PMID- 29033205
TI  - Differential Regulation of Evoked and Spontaneous Release by Presynaptic NMDA
      Receptors.
AB  - Presynaptic NMDA receptors (preNMDARs) control synaptic release, but it is not
      well understood how. Rab3-interacting molecules (RIMs) provide scaffolding at
      presynaptic active zones and are involved in vesicle priming. Moreover, c-Jun N
      terminal kinase (JNK) has been implicated in regulation of spontaneous release.
      We demonstrate that, at connected layer 5 pyramidal cell pairs of developing
      mouse visual cortex, Mg2+-sensitive preNMDAR signaling upregulates replenishment
      of the readily releasable vesicle pool during high-frequency firing. In
      conditional RIM1alphabeta deletion mice, preNMDAR upregulation of vesicle
      replenishment was abolished, yet preNMDAR control of spontaneous release was
      unaffected. Conversely, JNK2 blockade prevented Mg2+-insensitive preNMDAR
      signaling from regulating spontaneous release, but preNMDAR control of evoked
      release remained intact. We thus discovered that preNMDARs signal differentially
      to control evoked and spontaneous release by independent and non-overlapping
      mechanisms. Our findings suggest that preNMDARs may sometimes signal
      metabotropically and support the emerging principle that evoked and spontaneous
      release are distinct processes. VIDEO ABSTRACT.

PMID- 29033206
TI  - Pediatric Environmental Health: Using Data on Toxic Chemical Emissions in
      Practice.
AB  - : Children's unique behavioral and physiological characteristics can increase
      their exposure and susceptibility to environmental chemicals. The link between
      exposure to environmental chemicals and specific health outcomes, however, is
      often uncertain. This article introduces several resources to help health
      practitioners identify potential environmental exposures and risks related to
      toxic chemicals. It focuses on the U.S. Environmental Protection Agency's (EPA's)
      free and public environmental data, including the Toxics Release Inventory (TRI)
      data that contain information about toxics released to the environment. Three
      hypothetical case studies are presented to demonstrate how these data can help
      answer environmental exposure questions. The first case study illustrates a
      scenario where multiple patients in an area exhibit the same symptoms with a
      suspected link to environmental chemicals. The second case study illustrates a
      scenario where a patient with a confirmed exposure to a toxic chemical needs
      assistance with identifying potential environmental sources. And the third case
      study illustrates a scenario where a patient is concerned about the potential for
      future exposure to an environmental contaminant in a particular geographic area.
      Each case study includes contacts for follow-up questions, including the
      Pediatric Environmental Health Specialty Units (PEHSUs), EPA regional staff,
      state environmental agencies, and local health departments. These resources can
      help practitioners access and interpret environmental data, answer questions
      about potential exposures, and inform next steps if necessary. LEARNING
      OBJECTIVES: 

PMID- 29033207
TI  - Corrigendum to "The influence of different abutment materials on tissue
      regeneration after surgical treatment of peri-implantitis - A randomized
      controlled preclinical study" [J Cranio-Maxillo-Facial Surg 45 (2017) 1190-1196].

PMID- 29033208
TI  - Surgical treatment of synkinesis between smiling and eyelid closure.
AB  - Synkinetic movements are common among patients with incomplete recovery from
      facial palsy, with reported rates ranging from 9.1% to almost 100%. The authors
      propose the separation of the neural stimulus of the orbicularis oculi from that
      of the zygomatic muscular complex to treat eyelid closure/smiling synkinesis.
      This technique, associated with an anastomosis between the masseteric nerve and a
      central branch of the facial nerve, as well as with the use of a cross-facial
      nerve graft, resolves most of the spasms of the midface musculature, leading to a
      more relaxed tone when the mimic muscle is at rest and enhancing muscle excursion
      during voluntary and spontaneous smiling. Between 2011 and 2016, 18 patients
      affected by segmental paresis of the middle of the face underwent surgical
      treatment at the Maxillofacial Surgery Department of the San Paolo Hospital
      (Milan, Italy). Of these patients, 72.22% of cases with hypertone obtained
      partial to complete relaxation. Synkinesis was completely resolved in 83.33% of
      cases, and a significant improvement in facial movement was achieved in all
      patients. Neurorrhaphy of the masseteric nerve and the central branch of the
      facial nerve appears to produce favorable results. These initial data should be
      confirmed by further studies.

PMID- 29033209
TI  - A worldwide comparison of the management of T1 and T2 anterior floor of the mouth
      and tongue squamous cell carcinoma - Extent of surgical resection and
      reconstructive measures.
AB  - INTRODUCTION: Microvascular surgery following tumor resection has become an
      important field of oral maxillofacial surgery (OMFS). Following the results on
      general aspects of current reconstructive practice in German-speaking countries,
      Europe and worldwide, this paper presents specific concepts for the management of
      resection and reconstruction of T1/T2 squamous cell carcinoma (SCC) of the
      anterior floor of the mouth and tongue. METHODS: The DOESAK questionnaire was
      distributed in three different phases to a growing number of maxillofacial units
      worldwide. Within this survey, clinical patient settings were presented to
      participants and center-specific treatment strategies were evaluated. RESULTS: A
      total of 188 OMFS units from 36 different countries documented their treatment
      strategies for T1/T2 anterior floor of the mouth squamous cell carcinoma and
      tongue carcinoma. For floor of mouth carcinoma close to the mandible, a wide
      variety of concepts are presented: subperiosteal removal of the tumor versus
      continuity resection of the mandible and reconstruction ranging from locoregional
      closure to microvascular bony reconstruction. For T2 tongue carcinoma, concepts
      are more uniform. CONCLUSION: These results demonstrate the lack of evidence and
      the controversy of different guidelines for the extent of safety margins and
      underline the crucial need of global prospective randomized trials on this topic
      to finally obtain evidence for a common guideline based on a strong community of
      OMFS units.

PMID- 29033210
TI  - Measurements of air kerma index in computed tomography: A comparison among
      methodologies.
AB  - As CT exams impart high doses to patients in comparison to other radiologist
      techniques, reliable dosimetry is required. In this work, dosimetry in CT beams
      was carried out in terms of air kerma index in air or in a phantom measured by a
      pencil ionization chamber, thermoluminescent (TL) detectors and radiochromic
      film. Calibration results showed the low energy dependence of all three
      dosimetric systems for the 100-120kV range, the very high uncertainty of the TL
      dosimeters in comparison to the other systems and high nonlinearity response in
      terms of air kerma of the radiochromic film. Measurements with the three systems
      in a 120kV CT protocol showed an acceptable agreement among the weighted air
      kerma index values, but TL dosimeters presented the highest uncertainties in the
      values.

PMID- 29033211
TI  - Author Reply.

PMID- 29033212
TI  - Editorial Comment.

PMID- 29033213
TI  - Managing RISK when treating the injured runner with running retraining, load
      management and exercise therapy.

PMID- 29033214
TI  - The evaluation and management of respiratory disease in children with Down
      syndrome (DS).
AB  - Children with Down syndrome (DS) have wide range of respiratory problems.
      Although underlying abnormalities in the respiratory system are important causes
      of morbidity and mortality in children with DS, particularly in the young,
      abnormalities in other organ systems may also impact respiratory function. A
      comprehensive evaluation of the child with DS and respiratory disease may prevent
      short-term morbidity and mortality, and reduce the incidence of complications in
      the long term. This review provides an overview of the various causes of
      respiratory disease, and insight into some of the newer therapies available to
      treat obstructive sleep apnea, in this population.

PMID- 29033215
TI  - Treating resistant Pseudomonas aeruginosa lung disease in young children with
      cystic fibrosis.
AB  - Pseudomonas aeruginosa is a common bacterial pathogen in the evolution of
      bronchiectasis in cystic fibrosis. The appearance of resistant strains of
      pseudomonas is increasing with the earlier and more liberal use of a range of
      anti-pseudomonal antibiotics for the treatment of bacterial chest infections. The
      rationale for treatment and potential benefits of aggressive treatment of
      resistant strains of Pseudomonas aeruginosa from early in life are discussed.

PMID- 29033216
TI  - Anatomy of lower eyelid and eyelid-cheek junction.
AB  - BACKGROUND: Understanding the anatomy of the lower eyelid and the lid-cheek
      junction is important for surgical and non-surgical approaches. It is important
      to understand the correlation between the clinical presentation and the
      individual anatomy to direct an adequate treatment. METHODS: A review of the
      literature based on the authors experience combined with anatomical dissections
      was conducted to reveal the current concepts of the surgical and non-surgical
      anatomy. The various anatomical structures important for the understanding of the
      symptoms and the proposed treatment are described in this article. RESULTS: The
      anatomy of the lower eyelid and the lid-cheek junction has to be understood as a
      unit. Structures are continuous from the eyelid to the cheek influencing each
      other during aging. The concept of superficial, i.e. superficial to the
      orbicularis oculi muscle and deep facial fat compartments, i.e. deep to the
      orbicularis oculi muscle has to be applied in order to understand the relevant
      anatomy regarding the ligaments, fat compartments, muscular and tarsal structures
      and the vascularization. CONCLUSION: The understanding of the layered arrangement
      of the lower eyelid and eyelid-cheek junction anatomy enables practitioners to
      perform safe and effective surgical and non-surgical procedures.

PMID- 29033219
TI  - Sherwood correlation for dissolution of pooled NAPL in porous media.
AB  - The rate of interphase mass transfer from non-aqueous phase liquids (NAPLs)
      entrapped in the subsurface into the surrounding mobile aqueous phase is commonly
      expressed in terms of Sherwood (Sh) correlations that are expressed as a function
      of flow and porous media properties. Because of the lack of precise methods for
      the estimation of the interfacial area separating the NAPL and aqueous phases,
      most studies have opted to use modified Sherwood expressions that lump the
      interfacial area into the interphase mass transfer coefficient. To date, there
      are only two studies in the literature that have developed non-lumped Sherwood
      correlations; however, these correlations have undergone limited validation. In
      this paper controlled dissolution experiments from pooled NAPL were conducted.
      The immobile NAPL mass is placed at the bottom of a flow cell filled with porous
      media with water flowing horizontally on top. Effluent aqueous phase
      concentrations were measured for a wide range of aqueous phase velocities and for
      two different porous media. To interpret the experimental results, a two
      dimensional pore network model of the NAPL dissolution kinetics and aqueous phase
      transport was developed. The observed effluent concentrations were then used to
      compute best-fit mass transfer coefficients. Comparison of the effluent
      concentrations computed with the two-dimensional pore network model to those
      estimated with one-dimensional analytical solutions indicates that the analytical
      model which ignores the transport in the lateral direction can lead to under
      estimation of the mass transfer coefficient. Based on system parameters and the
      estimated mass transfer coefficients, non-lumped Sherwood correlations were
      developed and compared to previously published data. The developed correlations,
      which are a significant improvement over currently available correlations that
      are associated with large uncertainties, can be incorporated into future modeling
      studies requiring non-lumped Sh expressions.

PMID- 29033218
TI  - Early-onset Colorectal Cancer is Distinct From Traditional Colorectal Cancer.
AB  - BACKGROUND: Early-onset colorectal cancer (E-CRC) is increasing in incidence,
      unlike traditional CRC (T-CRC). We sought to characterize differences between E
      CRC and T-CRC. MATERIALS AND METHODS: Data sources included the Surveillance,
      Epidemiology, and End Results database, the Behavioral Risk Factor Surveillance
      Survey, and The Cancer Genome Atlas (TCGA). We compared demographics, tumor
      characteristics, and incidence of CRC in subjects aged 20 to 49 years (E-CRC)
      with those aged >= 50 years (T-CRC). We correlated the incidence of E-CRC and T
      CRC to CRC risk factors and age-dependent genomic characteristics of CRC using
      TCGA. RESULTS: A total of 369,796 CRCs were identified (2000-2011). E-CRC
      incidence has risen 1.4% per year, whereas T-CRC has declined 3.1% per year (P <
      .05). The incidence of E-CRC increases in a step-wise fashion from the ascending
      colon to rectum (P < 2.2e-16). E-CRC is more prevalent in male (53.7% vs. 46.4%;
      P < .001), Black (14.6% vs. 11.0%; P < .001), and Hispanic (14.7% vs. 8.3%; P <
      .001) patients. E-CRC presents with aggressive histology, including high-grade
      (1.5% vs. 1.3%; P < .001), signet ring cell (1.9% vs. 0.9%; P < .001), and
      mucinous carcinomas (8.9% vs. 8.1%; P < .001), and more often with distant
      disease (24.4% vs. 18.8%; P < .001). The geographic distribution of E-CRC mirrors
      United States counties with higher Black population densities. Unlike T-CRC, E
      CRC prevalence is not correlated with known CRC risk factors. E-CRC is associated
      with a lower rate of mutations than traditional CRC. Limitations of this study
      include E-CRC sample size for the TCGA analysis, as well as lack of comorbidity
      information and family history. CONCLUSION: E-CRC tumors are clinically,
      pathologically, and molecularly distinct from T-CRC. Further evaluation of
      genetic and molecular differences is necessary to understand the pathophysiology
      of E-CRC and to help target treatment/surveillance strategies.

PMID- 29033217
TI  - Normalization of the trapezius sEMG signal - a reliability study on women with
      and without neck-shoulder pain.
AB  - OBJECTIVE: To evaluate within- and between-days reliability of two normalization
      methods of surface electromyography (sEMG) recordings of the trapezius muscle.
      METHODS: Nineteen women were allocated into 2 groups (healthy and with neck
      shoulder pain). The sEMG was recorded in two sessions with 7 days in between
      sessions. The four portions of the trapezius muscle (the clavicular and acromial
      fibers of the upper trapezius, the middle and the lower trapezius) were evaluated
      during maximal and submaximal isometric voluntary contractions. The within- and
      between-days reliability of both maximal and submaximal contractions were
      assessed through Intraclass Correlation Coefficient (ICC(2,1) was used for within
      day analyses of both maximal and submaximal contractions, and for between-days
      analyses of maximal contractions while ICC(2,3) was used for between-days
      analyses of submaximal contractions), Coefficient of Variation, Standard Error of
      Measurement, and Bland-Altman analysis. RESULTS: In general, submaximal
      contractions presented higher within-day reliability, with higher ICC values
      (e.g., middle trapezius - mean of 0.97), smaller Coefficient of Variation and
      Standard Error of Measurement ranges compared to maximal contractions (ICC
      values, e.g. for middle trapezius - mean of 0.94) in both groups. The same
      pattern was observed for between-days analyses, with submaximal contractions
      presenting higher ICC values (e.g., middle trapezius - mean of 0.84), smaller
      Coefficient of Variation and Standard Error of Measurement ranges than maximal
      contractions (ICC values, e.g. for middle trapezius - mean of 0.73) in both
      groups. CONCLUSION: Submaximal contractions are recommended for normalization
      procedures of trapezius sEMG, in both subjects with neck-shoulder pain and
      healthy individuals.

PMID- 29033220
TI  - Transport and potential attenuation of nitrogen in shallow groundwaters in the
      lower Rangitikei catchment, New Zealand.
AB  - Intensive agricultural activities are generally associated with nitrogen leaching
      from agricultural soils, and this nitrogen has the potential to percolate and
      contaminate groundwater and surface waters. We assessed surface water and
      groundwater interactions, and nitrogen leaching and its potential attenuation in
      shallow groundwater in the lower Rangitikei River catchment (832km2), New
      Zealand. We combined regional- and local-scale field surveys and experiments,
      nutrient budget modelling, and hydraulic and geochemical methods, to gain an
      insight into leaching, transformation and transport of nitrogen via groundwaters
      to the river in the study area. Concurrent river flow gaugings (in January 2015)
      and a piezometric map, developed from measured depths to groundwater in 110 bores
      (in October 2014), suggest groundwater discharges to the Rangitikei River in the
      upper parts of the study area, while there is groundwater recharge near the
      coast. The groundwater redox characterisation, based on sampling and analysis of
      15 mostly shallow bores (<30m below ground level (bgl)), suggests groundwater
      across the lower Rangitikei catchment in general is under anoxic/reduced
      conditions. The groundwater typically has low dissolved oxygen (DO)
      concentrations (<1mg/L), suggesting the subsurface environment is conducive to
      potential attenuation by 'denitrification' of NO3-N in groundwater. We further
      measured NO3-N attenuation in shallow groundwater piezometers (3-6mbgl) using
      single-well push-pull tests. We found generally low levels (<0.5mg/L) of NO3-N in
      shallow groundwater piezometers (>5mbgl), despite being installed under intensive
      land uses, such as dairying and cropping. Our in-field push-pull tests showed NO3
      N reduction at four shallow groundwater piezometers, with the rates of reduction
      varying from 0.04mgNL-1h-1 to 1.57mgNL-1h-1. This highlights the importance of a
      sound understanding of not only the sources, but also transport and
      transformation, or fate, of nutrients leached from farms, to mitigate the likely
      impacts of land use on water quality and ecosystem health in agricultural
      catchments.

PMID- 29033221
TI  - On the role of visual experience in mathematical development: Evidence from blind
      mathematicians.
AB  - Advanced mathematical reasoning, regardless of domain or difficulty, activates a
      reproducible set of bilateral brain areas including intraparietal, inferior
      temporal and dorsal prefrontal cortex. The respective roles of genetics,
      experience and education in the development of this math-responsive network,
      however, remain unresolved. Here, we investigate the role of visual experience by
      studying the exceptional case of three professional mathematicians who were blind
      from birth (n=1) or became blind during childhood (n=2). Subjects were scanned
      with fMRI while they judged the truth value of spoken mathematical and
      nonmathematical statements. Blind mathematicians activated the classical network
      of math-related areas during mathematical reflection, similar to that found in a
      group of sighted professional mathematicians. Thus, brain networks for advanced
      mathematical reasoning can develop in the absence of visual experience.
      Additional activations were found in occipital cortex, even in individuals who
      became blind during childhood, suggesting that either mental imagery or a more
      radical repurposing of visual cortex may occur in blind mathematicians.

PMID- 29033222
TI  - Processing of structural neuroimaging data in young children: Bridging the gap
      between current practice and state-of-the-art methods.
AB  - The structure of the brain is subject to very rapid developmental changes during
      early childhood. Pediatric studies based on Magnetic Resonance Imaging (MRI) over
      this age range have recently become more frequent, with the advantage of
      providing in vivo and non-invasive high-resolution images of the developing
      brain, toward understanding typical and atypical trajectories. However, it has
      also been demonstrated that application of currently standard MRI processing
      methods that have been developed with datasets from adults may not be appropriate
      for use with pediatric datasets. In this review, we examine the approaches
      currently used in MRI studies involving young children, including an overview of
      the rationale for new MRI processing methods that have been designed specifically
      for pediatric investigations. These methods are mainly related to the use of age
      specific or 4D brain atlases, improved methods for quantifying and optimizing
      image quality, and provision for registration of developmental data obtained with
      longitudinal designs. The overall goal is to raise awareness of the existence of
      these methods and the possibilities for implementing them in developmental
      neuroimaging studies.

PMID- 29033223
TI  - Who gets a pouch after colectomy in New York state and why?
AB  - BACKGROUND: This study identified variation and factors associated with ileal
      pouch-anal anastomosis after total colectomy for ulcerative colitis. METHODS: The
      Statewide Planning & Research Cooperative System was used to identify patients
      with ulcerative colitis who underwent total colectomy in New York state from 2000
      2013. Bivariate and mixed-effects multivariable analyses were performed to assess
      patient, surgeon, and hospital-level factors as well as surgeon and hospital
      level variation associated with ileal pouch-anal anastomosis after total
      colectomy. RESULTS: Across 2,203 patients, the rate of ileal pouch-anal
      anastomosis was 34%. Overall, 465 surgeons and 148 hospitals performed at least
      one total colectomy for ulcerative colitis from 2000-2013, and 178 surgeons and
      80 hospitals performed at least one ileal pouch-anal anastomosis for ulcerative
      colitis during the study period. The median rate of ileal pouch-anal anastomosis
      creation was 14% (range = 6% to 69%) across surgeons and 14% (range = 7% to 63%)
      across hospitals. Patient-level factors independently associated with ileal pouch
      anal anastomosis were younger age, lower comorbidity burden, and elective total
      colectomy. Surgeon and hospital-level factors independently associated with ileal
      pouch-anal anastomosis were colorectal surgery board-certification, surgeon ileal
      pouch-anal anastomosis volume, and hospital ileal pouch-anal anastomosis volume.
      Patient-level factors explained 43% of the surgeon and 47% of the hospital
      variation in ileal pouch-anal anastomosis creation while surgeon-level factors
      explained 26% of the surgeon and 21% of the hospital variation. CONCLUSION: These
      findings suggest that variation in ileal pouch-anal anastomosis creation for
      ulcerative colitis is influenced largely by provider practices/preferences or
      lack of referral of patients after colectomy to surgeons and centers that perform
      ileal pouch-anal anastomosis. Providers and hospitals that do not routinely
      perform ileal pouch-anal anastomosis should refer patients to centers with ileal
      pouch-anal anastomosis expertise after total colectomy.

PMID- 29033224
TI  - Downstaging therapy followed by liver transplantation for hepatocellular
      carcinoma beyond Milan criteria.
AB  - BACKGROUND: Orthotopic liver transplantation is a curative treatment for
      hepatocellular carcinoma within Milan criteria, but these criteria preclude many
      patients from transplant candidacy. Recent studies have demonstrated that
      downstaging therapy can reduce tumor burden to meet conventional criteria. The
      present study reports a single-center experience with tumor downstaging and its
      effects on post-orthotopic liver transplantation outcomes. METHODS: All patients
      with hepatocellular carcinoma who were evaluated by our multidisciplinary liver
      services team from 2012 to 2016 were identified (N = 214). Orthotopic liver
      transplantation candidates presenting outside of Milan criteria at initial
      radiographic diagnosis and/or an initial alpha-fetoprotein >400 ng/mL were
      categorized as at high risk for tumor recurrence and post-transplant mortality.
      RESULTS: Of the 214 patients newly diagnosed with hepatocellular carcinoma, 73
      (34.1%) eventually underwent orthotopic liver transplantation. The majority of
      patients who did not undergo orthotopic liver transplantation were deceased or
      lost to follow-up (47.5%), with 14 of 141 (9.9%) currently listed for
      transplantation. Among transplanted patients, 21 of 73 (28.8%) were considered
      high-risk candidates. All 21 patients were downstaged to within Milan criteria
      with an alpha-fetoprotein <400 ng/mL before orthotopic liver transplantation,
      through locoregional therapies. Recurrence of hepatocellular carcinoma was higher
      but acceptable between downstaged high-risk and traditional candidates (9.5% vs
      1.9%; P > .05) at a median follow-up period of 17 months. Downstaged high-risk
      candidates had a similar overall survival compared with those transplanted within
      Milan criteria (log-rank P > .05). CONCLUSIONS: In highly selected cases,
      patients with hepatocellular carcinoma outside of traditional criteria for
      orthotopic liver transplantation may undergo downstaging therapy in a
      multidisciplinary fashion with excellent post-transplant outcomes. These data
      support an aggressive downstaging approach for selected patients who would
      otherwise be deemed ineligible for transplantation.

PMID- 29033226
TI  - The Importance of Palliative Care for Dementia.

PMID- 29033225
TI  - Nomograms for prediction of long-term survival in elderly patients after partial
      hepatectomy for hepatocellular carcinoma.
AB  - BACKGROUND: Partial hepatectomy is an important treatment for elderly patients
      with hepatocellular carcinoma. However, prediction of long-term outcomes of an
      individual elderly patient after partial hepatectomy still is lacking. This study
      aimed to develop 2 nomograms to pre- or postoperatively predict overall survival
      for these patients. METHODS: Of the 528 elderly patients (aged >=65 years) who
      underwent partial hepatectomy for hepatocellular carcinoma at the Eastern
      Hepatobiliary Surgery Hospital between 2008 and 2011, 425 patients served as a
      training cohort to develop pre- and postoperative nomograms, and the remaining
      103 patients comprised a validation cohort. The Cox proportional hazards model
      was used for univariate and multivariable analyses of tumor recurrence and
      overall survival. Discrimination and calibration of the models were measured
      using the concordance index, calibration plots, and Kaplan-Meier curves. RESULTS:
      Based on preoperative data, the independent risk factors of overall survival were
      age >=75 years, Charlson score, alpha-fetoprotein >=20 MUg/L, hepatitis B virus
      deoxyribonucleic acid >=104 IU/mL, and tumor diameter. Based on postoperative
      data, nonanatomic hepatectomy, absence of tumor encapsulation, and presence of
      microvascular invasion were additional independent risk factors. These
      independent predictors were incorporated into the pre- and postoperative
      nomograms, respectively. The concordance indexes of the 2 nomograms for overall
      survival prediction were 0.70 (95% confidence interval, 0.67-0.74) and 0.72 (0.69
      0.78), respectively. Both nomograms accurately predicted 1-, 3-, and 5-year
      overall survival probability, and their predictive performances were optimally
      validated. CONCLUSION: The proposed 2 nomograms showed good individualized
      predictive performance in elderly patients with hepatocellular carcinoma before
      and after partial hepatectomy.

PMID- 29033227
TI  - Spasticity and hyperselective neurectomy in the upper limb.
AB  - Spasticity is a complex pathology, both in terms of assessment and treatment.
      This article focuses on the clinical examination (objective, capacity,
      performance and function), which is key for choosing a treatment and can be
      helped by botulinum toxin injections. The treatment involves physical therapy,
      occupational therapy, medications and surgery. Neurectomy has been used in the
      upper limb since 1912 and is one of the therapeutic options for spasticity. This
      treatment is usually reserved for nonfunctional hands. Cadaver studies have
      helped us better understand nerve anatomy and improve the hyperselective
      neurectomy (HSN) technique. This article describes the history of neurectomy, how
      anatomical dissections apply to surgery, the HSN technique in the
      musculocutaneous nerve, median nerve and ulnar nerve and results of preliminary
      prospective studies. Spasticity, mobility, performance and function were
      evaluated a few months after HSN and about 12 months later to assess the
      permanence of the results in children and adult spastic patients. No matter the
      nerve or function targeted (elbow extension, wrist extension, or supination),
      spasticity was reduced with improvements in the functional House score and
      appeared stable at the last follow-up. HSN seems to be a good, reliable
      therapeutic option for spasticity, including functional hands.

PMID- 29033228
TI  - Epigenetics: A way to bridge the gap between biological fields.
AB  - The concept of epigenetics has evolved since Waddington defined it from the late
      1930s as the study of the causal mechanisms at work in development. It has become
      a multi-faceted notion with different meanings, depending on the disciplinary
      context it is used. In this article, we first analyse the transformations of the
      concept of epigenetics, from Waddington to contemporary accounts, in order to
      identify its different meanings and traditions, and to come up with a typology of
      epigenetics throughout its history. Second, we show on this basis that
      epigenetics has progressively turned its main focus from biological problems
      regarding development, toward issues concerning evolution. Yet, both these
      different epistemological aspects of epigenetics still coexist. Third, we claim
      that the classical opposition between epigenesis and preformationism as ways of
      thinking about the developmental process is part of the history of epigenetics
      and has contributed to its current various meanings. With these objectives in
      mind, we first show how Waddington introduced the term "epigenetics" in a
      biological context in order to solve a developmental problem, and we then build
      on this by presenting Nanney's, Riggs' and Holliday's definitions, which form the
      basis for the current conception of "molecular epigenetics". Then, we show that
      the evo-devo research field is where some particular uses of epigenetics have
      started shifting from developmental issues to evolutionary problems. We also show
      that epigenetics has progressively focused on the issue of epigenetic inheritance
      within the Extended Evolutionary Synthesis' framework. Finally, we conclude by
      presenting a typology of the different conceptions of epigenetics throughout
      time, and analyse the connections between them. We argue that, since Waddington,
      epigenetics, as an integrative research area, has been used to bridge the gap
      between different biological fields.

PMID- 29033230
TI  - History of traction.

PMID- 29033229
TI  - Analysis of Recurrent Stroke Volume and Prognosis between Warfarin and Four Non
      Vitamin K Antagonist Oral Anticoagulants' Administration for Secondary Prevention
      of Stroke.
AB  - OBJECTIVE: We investigated recurrent stroke volume with nonvalvular atrial
      fibrillation (NVAF) patients treated with non-vitamin K antagonist oral
      anticoagulants (NOACs) about clinical backgrounds and number of recurrent stroke.
      METHODS: We administered 4 NOACs, dabigatran, rivaroxaban, apixaban, and edoxaban
      in 101 postcardioembolic strokes with NVAF. In a retrospective study, we measured
      recurrent stroke volume with magnetic resonance imaging volumetric software and
      compared them between 10 vitamin K anticoagulant (VKA: warfarin) cases and 13
      NOAC cases under anticoagulant therapy. RESULTS: Of 101 cases, 31 were started
      with a VKA and switched to NOACs after 10 recurrent strokes. Other 70 cases were
      directly started with NOACs and 13 cases with NOACs as first anticoagulants had
      recurrent stroke. The frequency of recurrent stroke during anticoagulant therapy
      is not different between the VKA group and the 3 NOACs group. Recurrent stroke
      volume is significantly larger in the VKA group (26.4 cm3) than in the NOACs
      group (1.2 cm3). CONCLUSIONS: Secondary prevention with NOACs after stroke might
      be more beneficial than a VKA by reducing recurrent infarct volume.

PMID- 29033232
TI  - Design, synthesis and biological evaluation of phthalimide-alkylamine derivatives
      as balanced multifunctional cholinesterase and monoamine oxidase-B inhibitors for
      the treatment of Alzheimer's disease.
AB  - A series of novel phthalimide-alkylamine derivatives were synthesized and
      evaluated as multi-functions inhibitors for the treatment of Alzheimer's disease
      (AD). The results showed that compound TM-9 could be regarded as a balanced multi
      targets active molecule. It exhibited potent and balanced inhibitory activities
      against ChE and MAO-B (huAChE, huBuChE, and huMAO-B with IC50 values of 1.2MUM,
      3.8MUM and 2.6 MUM, respectively) with low selectivity. Both kinetic analysis of
      AChE inhibition and molecular modeling study suggested that TM-9 binds
      simultaneously to the catalytic active site and peripheral anionic site of AChE.
      Interestingly, compound TM-9 abided by Lipinski's rule of five. Furthermore, our
      investigation proved that TM-9 indicated weak cytotoxicity, and it could cross
      the blood-brain barrier (BBB) in vitro. The results suggest that compound TM-9,
      an interesting multi-targeted active molecule, offers an attractive starting
      point for further lead optimization in the drug-discovery process against
      Alzheimer's disease.

PMID- 29033231
TI  - The combination of dynapenia and abdominal obesity as a risk factor for worse
      trajectories of IADL disability among older adults.
AB  - BACKGROUND/OBJECTIVES: The concept of dynapenic obesity has been gaining great
      attention recently. However, there is little epidemiological evidence
      demonstrating that dynapenic abdominal obese individuals have worse trajectories
      of disability than those with dynapenia and abdominal obesity alone. Our aim was
      to investigate whether dynapenia combined with abdominal obesity can result in
      worse trajectories of instrumental activities of daily living (IADL) among
      English and Brazilian older adults over eight and ten years of follow-up,
      respectively. METHODS: We used longitudinal data from 3374 participants from the
      English Longitudinal Study of Ageing (ELSA) and 1040 participants from the
      Brazilian Health, Well-being and Aging Study (SABE) who were free from disability
      as assessed by IADL at baseline. IADL disability was defined herein as a
      difficulty to perform the following: preparing meals, managing money, using
      transportation, shopping, using the telephone, house cleaning, washing clothes,
      and taking medications according to the Lawton IADL modified scale. The study
      population in each country was categorized into non-dynapenic/non-abdominal obese
      (reference group), abdominal obese, dynapenic and dynapenic abdominal obese
      according to their handgrip strength (<26 kg for men and <16 kg for women) and
      waist circumference (>102 cm for men and >88 cm for women). We used generalized
      linear mixed models with IADL as the outcome. RESULTS: The estimated change over
      time in IADL disability was significantly higher for participants with dynapenic
      abdominal obesity compared to those with neither condition in both cohorts (ELSA:
      +0.023, 95% CI = 0.012-0.034, p < 0.001; SABE: +0.065, 95% CI = 0.038-0.091, p <
      0.001). Abdominal obesity was also associated with changes over time in IADL
      disability (ELSA: +0.009, 95% CI = 0.002-0.015, p < 0.05; SABE: +0.021, 95% CI =
      0.002-0.041, p < 0.05), which was not observed for dynapenia. CONCLUSIONS:
      Abdominal obesity is an important risk factor for IADL decline but participants
      with dynapenic abdominal obesity had the highest rates of IADL decline over time
      among English and Brazilian older adults.

PMID- 29033233
TI  - Design, synthesis and biological evaluation of 2-acetyl-5-O-(amino-alkyl)phenol
      derivatives as multifunctional agents for the treatment of Alzheimer's disease.
AB  - A series of 2-acetyl-5-O-(amino-alkyl)phenol derivatives was designed,
      synthesized and evaluated as multi-function inhibitors for the treatment of
      Alzheimer's disease (AD). The results revealed that compound TM-3 indicated
      selective AChE inhibitory potency (eeAChE, IC50 = 0.69 MUM, selective index (SI)
      = 32.7). Both kinetic analysis of AChE inhibition and molecular modeling study
      suggested that TM-3 could simultaneously bind to the catalytic active site and
      peripheral anionic site of AChE. And TM-3 was also a highly selective MAO-B
      inhibitor (IC50 = 6.8 MUM). Moreover, TM-3 could act as antioxidant (ORAC value
      was 1.5eq) and neuroprotectant, as well as a selective metal chelating agent.
      More interestingly, compound TM-3 could cross the blood-brain barrier (BBB) in
      vitro and abided by Lipinski's rule of five. Therefore, compound TM-3, a
      promising multi-targeted active molecule, offers an attractive starting point for
      further lead optimization in the drug-discovery process against AD.

PMID- 29033234
TI  - Antibacterial constituents of the plant family Amaryllidaceae.
AB  - There is a pressing need in antibiotic drug discovery for new drugs to
      counterbalance the effects of multidrug resistance. Plants represent a viable
      platform for such endeavors owing to their traditional relevance in infectious
      disease therapies as well as their vast chemical resources. As many as fifty
      different species of the Amaryllidaceae are discernible with such functions in
      traditional medicine, thirty-nine of which have been subjected to pharmacological
      evaluations. Submicromolar antibacterial activities for several of these plants
      have been the driving force behind studies targeting their active constituents.
      This review accounts for close to a hundred of such entities, mainly isoquinoline
      alkaloids, which have been the focus in assays of thirty different bacterial
      pathogens. Promising activities were detected in several instances, although
      disappointingly the submicromolar level could not be breached. Also considered
      are structure-activity relationships which have emerged within the various groups
      of Amaryllidaceae alkaloids.

PMID- 29033235
TI  - Ruthenium(II)- and copper(I)-catalyzed synthesis of click-xylosides and
      assessment of their glycosaminoglycan priming activity.
AB  - Xylosides are small molecules that serve as primers of glycosaminoglycan
      biosynthesis. Xyloside mediated modulation of biological functions depends on the
      extent of priming activity and fine structures of primed GAG chains. In earlier
      studies, copper (Cu) catalyzed synthesis of click-xylosides and their priming
      activity were extensively documented. In the current study, ruthenium (Ru)
      mediated catalysis was employed to synthesize xylosides with a 1,5-linkage
      between the xylose and the triazole ring instead of a 1,4-linkage as found in Cu
      catalyzed click-xyloside synthesis. Mono- and bis-click-xylosides were
      synthesized using each catalytic method and their glycosaminoglycan priming
      activity was assessed in vitro using a cellular system. Ru-catalyzed click
      xylosides showed a higher priming activity as measured by incorporation of
      radioactive sulfate into primed glycosaminoglycan chains. This study demonstrates
      that altering the linkage of the aglycone to the triazole ring changes the
      priming activity. Computational modeling provides a molecular rationale for
      higher priming ability of Ru-mediated click-xylosides. Higher GAG priming
      activity is attributed to the formation of more stable interactions between the
      1,5-linked xylosides and beta-1,4-galactosyltransferase 7 (beta4GalT7).

PMID- 29033236
TI  - Pharmaconutrition with intravenous selenium in intensive care: The end of an era?

PMID- 29033237
TI  - Coronary artery calcium-guided prevention: The time is now!

PMID- 29033238
TI  - Dexrazoxane prevents skin necrosis in non-target embolization of falciform artery
      during transcatheter arterial chemoembolization (TACE).

PMID- 29033239
TI  - Socioeconomic Factors, Health Behavior, and Late-Stage Diagnosis of Breast
      Cancer: Considering the Impact of Delay in Diagnosis.
AB  - BACKGROUND: Stage of cancer at diagnosis is one of the most important factors in
      patient prognosis. By controlling for diagnostic delay, this study aimed to
      identify factors associated with late-stage breast cancer (BC). PATIENTS AND
      METHODS: From November 2014 to January 2017, required information on 497 patients
      who were newly diagnosed with BC was obtained from patients' medical records.
      Logistic regression was used to measure the association between cancer stage and
      study variables. RESULTS: Only 18.3% of patients were diagnosed at stage I. The
      rest were diagnosed at stage II (45.5%) or higher (36.2%). Among those with <= 3
      months' diagnostic delay, age (odds ratio [OR] = 0.96; 95% confidence interval
      [CI], 0.93-0.99), place of residence (OR urban/rural = 1.72; 95% CI, 1.42-1.93),
      income (OR high/low = 0.27; 95% CI, 0.10-0.72), performing breast self
      examination (OR yes/no = 0.51; 95% CI, 0.0.26 -0.98), smoking (OR yes/no = 2.23;
      95% CI, 1.37-3.62), history of chest X-ray (OR yes/no = 1.40; 95% CI, 1.16-1.98),
      presence of chronic diseases (OR yes/no = 1.73; 95% CI, 1.36-5.48), and, for
      those with a delay of > 3 months, marriage age (OR = 0.83; 95% CI, 0.73-0.94),
      income (OR high/low = 0.07; 95% CI, 0.008-0.63), family history of BC (OR = 3.82;
      95% CI, 1.05-5.05), daily exercise (OR < 10/10-20 = 0.10; 95% CI, 0.01-0.67), and
      presence of chronic diseases (OR yes/no = 1.77; 95% CI, 1.73-5.07), were
      associated with late-stage of cancer. CONCLUSION: Shortening the diagnostic delay
      can help patients receive medical treatment at an earlier disease stage,
      resulting in better prognosis. Smokers, younger women, and those with chronic
      conditions or a family history of BC should take extra caution, as they may have
      worse prognosis if diagnosed with cancer.

PMID- 29033240
TI  - Single Nucleotide Polymorphisms in the Acylphosphatase 2 Gene and The SNP-SNP
      Interactions on the Risk of Breast Cancer in Chinese Han Women.
AB  - INTRODUCTION: The purpose of this study was to investigate the impact of single
      nucleotide polymorphisms (SNPs) in the acylphosphatase 2 gene and the SNP-SNP
      interactions on breast cancer (BC) risk in Chinese Han women. PATIENTS AND
      METHODS: A logistic regression model was used to examine the association between
      SNPs and BC risk. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were
      calculated. Generalized multifactor dimensionality reduction was employed to
      analyze the SNP-SNP interaction. RESULTS: Logistic regression analysis showed
      that BC risk was significantly higher in carriers with the rs1682111-A allele
      than those with the TT genotype (TA + AA vs. TT; adjusted OR, 1.47; 95% CI, 1.21
      1.92). In addition, we also found that BC risk was significantly higher in
      carriers with the rs10439478-C allele than those with the AA genotype (AC + CC
      vs. AA); adjusted OR, 1.67; 95% CI, 1.29-2.11. We found a significant 2-locus
      model (P = .0010) involving rs1682111 and rs10439478; the cross-validation
      consistency of this model was 10 of 10, and the testing accuracy was 60.11%.
      Participants with the TA or AA of rs1682111 and the AC or CC of rs10439478
      genotype have the highest BC risk, compared with subjects with the TT of
      rs1682111 and the AA of rs10439478 genotype (OR, 2.52; 95% CI, 1.67-3.44), after
      covariate adjustment for gender, age, age at menarche, number of children, and
      body mass index. CONCLUSIONS: Minor allele of rs1682111 and rs10439478 and its
      interaction were associated with increased BC risk.

PMID- 29033241
TI  - Gender Differences in the Authorship of Original Research in Pediatric Journals,
      2001-2016.
AB  - OBJECTIVES: To examine the gender of authors of original research in 3 high
      impact pediatric journals between 2001 and 2016, given the importance of
      publishing on academic promotion, and to compare authorship gender with the
      percentage of women on editorial boards and with academic faculty composition.
      STUDY DESIGN: We assessed the prevalence of female first and senior (last-listed)
      authorship of original research articles published in 3 pediatric-focused
      journals Pediatrics, JAMA Pediatrics (entitled Archives of Pediatric and
      Adolescent Medicine until 2013), and The Journal of Pediatrics. We also examined
      the gender breakdown of the main editors and the broader editorial boards of
      these journals. In addition, we examined whether junior female faculty co
      authored with male or female senior faculty. RESULTS: Of 3895 original articles,
      22 were excluded because the gender of either the first or senior author could
      not be determined from the name. An analysis of authorship by year showed
      increasing female representation across the selected journals in both first
      (39.8% in 2001, 57.7% in 2016) and senior (28.6% in 2001, 38.1% in 2016) authors,
      respectively. Editorial boards also showed increasing female representation
      (17.8% in 2001 to 39.8% in 2016). Junior female faculty were more likely to co
      author with senior female women (female first and last author); the gap remained
      unchanged despite the increasing number of women entering pediatrics.
      CONCLUSIONS: Women are underrepresented as authors and editors, although the gap
      is closing. Junior women are less likely to co-author with senior men, which may
      be a disservice given current gender disparities in promotion and leadership.

PMID- 29033243
TI  - Epilepsy by Any Other Name Would (Not!) Smell as Sweet.

PMID- 29033242
TI  - Weight Trajectories from Birth and Bone Mineralization at 7 Years of Age.
AB  - OBJECTIVE: To assess whether different trajectories of weight gain since birth
      influence bone mineral content (BMC) and areal bone mineral density (aBMD) at 7
      years of age. STUDY DESIGN: We studied a subsample of 1889 children from the
      Generation XXI birth cohort who underwent whole-body dual-energy radiograph
      absorptiometry. Weight trajectories identified through normal mixture modeling
      for model-based clustering and labeled "normal weight gain," "weight gain during
      infancy," "weight gain during childhood," and "persistent weight gain" were used.
      Differences in subtotal BMC, aBMD, and size-corrected BMC (scBMC) at age 7 years
      according to weight trajectories were estimated through analysis of covariance.
      RESULTS: Compared with the "normal weight gain" trajectory, children in the
      remaining trajectories had significantly greater BMC, aBMD, and scBMC at age 7
      years, with the strongest associations for "persistent weight gain" (girls [BMC:
      674.0 vs 559.8 g, aBMD: 0.677 vs 0.588 g/cm2, scBMC: 640.7 vs 577.4 g], boys
      [BMC: 689.4 vs 580.8 g, aBMD: 0.682 vs 0.611 g/cm2, scBMC: 633.0 vs 595.6 g]).
      After adjustment for current weight, and alternatively for fat and lean mass,
      children with a "weight gain during childhood" trajectory had greater BMC and
      aBMD than those with a "normal weight gain" trajectory, although significant
      differences were restricted to girls (BMC: 601.4 vs 589.2 g, aBMD: 0.618 vs 0.609
      g/cm2). CONCLUSION: Overall, children following a trajectory of persistent weight
      gain since birth had clearly increased bone mass at 7 years, but weight gain
      seemed slightly more beneficial when it occurred later rather than on a normal
      trajectory during the first 7 years of life.

PMID- 29033244
TI  - iASPP Is an Antioxidative Factor and Drives Cancer Growth and Drug Resistance by
      Competing with Nrf2 for Keap1 Binding.
AB  - Reactive oxygen species (ROS) have emerged as important signaling molecules that
      play crucial roles in carcinogenesis and cytotoxic responses. Nrf2 is the master
      regulator of ROS balance. Thus, uncovering mechanisms of Nrf2 regulation is
      important for the development of alternative treatment strategies for cancers.
      Here, we demonstrate that iASPP, a known p53 inhibitor, lowers ROS independently
      of p53. Mechanistically, iASPP competes with Nrf2 for Keap1 binding via a DLT
      motif, leading to decreased Nrf2 ubiquitination and increased Nrf2 accumulation,
      nuclear translocation, and antioxidative transactivation. This iASPP-Keap1-Nrf2
      axis promotes cancer growth and drug resistance both in vitro and in vivo. Thus,
      iASPP is an antioxidative factor and represents a promising target to improve
      cancer treatment, regardless of p53 status.

PMID- 29033245
TI  - Clinical comparison of alfaxalone, ketamine and propofol following medetomidine
      and methadone in dogs.
AB  - OBJECTIVE: To compare the clinical effects of alfaxalone, ketamine and propofol
      in dogs following premedication with medetomidine and methadone. STUDY DESIGN:
      Prospective, 'blinded' and randomized clinical study. ANIMALS: A total of 75 male
      dogs presented for neutering at a charity clinic. METHODS: Dogs were allocated to
      be administered alfaxalone, ketamine or propofol following premedication with
      medetomidine (20 MUg kg-1) and methadone (0.2 mg kg-1). Dogs were temperament
      scored prior to premedication. Quality of sedation, induction of anaesthesia,
      recovery and recovery environment were scored by simple descriptive scales.
      Physiological variables during anaesthesia were recorded. Continuous numerical
      data were analysed using analysis of variance with repeated measures as
      necessary. Nonparametric data were analysed using Kruskal-Wallis tests and
      multiple comparisons using Dunn's test. Statistical significance was set at p <
      0.05. RESULTS: The mean (+/- standard deviation) dose of alfaxalone was 0.6 +/-
      0.2 mg kg-1, that for ketamine was 1.5 +/- 0.7 mg kg-1 and that for propofol was
      0.8 +/- 0.3 mg kg-1. Alfaxalone inductions were significantly smoother compared
      to ketamine but not to propofol. Only one of 75 of the inductions was deemed
      poor. There were no differences in cardiopulmonary variables between groups
      except immediately after induction of anaesthesia. There were no differences in
      quality of recovery between groups. CONCLUSIONS AND CLINICAL RELEVANCE: All three
      induction agents provided reliable, predictable anaesthesia conditions that were
      clinically indistinguishable and ideal for teaching anaesthesia skills. The
      medetomidine and methadone premedication resulted in profound, heavy sedation and
      the quality of induction of anaesthesia was better with alfaxalone compared to
      ketamine. No significant difference in induction quality was detected between
      alfaxalone and proprofol or propofol and ketamine, and these findings are likely
      to be of limited clinical significance when choosing an induction agent.

PMID- 29033246
TI  - Effect of choline chloride premedication on xylazine-induced hypoxaemia in sheep.
AB  - OBJECTIVE: To determine the anti-inflammatory efficacy of choline in vivo and in
      vitro and to investigate the anti-inflammatory mechanisms of choline. STUDY
      DESIGN: Randomized, controlled studies. ANIMALS: In vivo trials used 16 Romney
      sheep. In vitro experiments utilized RAW 264.7 mouse macrophage cells. METHODS:
      Hypoxaemia induced in 16 sheep by intravenous (IV) injection of 50 MUg kg-1
      xylazine, an alpha-2 agonist, was measured in sheep at 0, 1 and 4 minutes using
      arterial blood gas analysis with and without 50 mg kg-1 IV choline chloride
      premedication. Cell culture studies used enzyme-linked immunosorbent assay to
      measure the release of tumour necrosis factor (TNF-alpha) from lipopolysaccharide
      (LPS) stimulated macrophages with and without choline chloride premedication. TNF
      alpha release was compared to thalidomide suppressed and untreated cells.
      RESULTS: Choline premedication in sheep mitigated a reduction in arterial partial
      pressure of oxygen (PaO2) but did not prevent development of clinically
      significant hypoxaemia. Decrease in mean PaO2 of choline treated sheep was 6.36
      kPa (47.7 mmHg) compared to 9.81 kPa (73.6 mmHg) in control sheep. In vitro
      studies demonstrate that choline administered concurrent with LPS activation did
      not significantly suppress TNF-alpha expression but that treatment of cells with
      choline 10 minutes prior to LPS activation did significantly suppress TNF-alpha
      expression. Choline pretreated cells expressed 23.99 +/- 4.52 ng mg-1 TNF-alpha
      while LPS only control cells expressed 33.83 +/- 3.20 ng mg-1. CONCLUSIONS:
      Choline is able to prevent macrophage activation in vitro when administered prior
      to LPS activation and may reduce hypoxaemia in sheep developing pulmonary oedema
      after xylazine administration. This effect requires premedication with choline.
      CLINICAL RELEVANCE: Pharmacological manipulation of autonomic inflammatory
      responses holds promise for the treatment of inflammation. However, the complex
      cellular mechanisms involved in this reflex means that an adequate therapy should
      approach multiple pathways and mechanisms of the inflammatory response.

PMID- 29033247
TI  - Progressive reticulate skin pigmentation and anonychia in a patient with bone
      marrow failure.
AB  - KEY TEACHING POINTS.

PMID- 29033248
TI  - Use of oral antidepressants in patients with chronic pruritus: A systematic
      review.
AB  - BACKGROUND: Chronic pruritus is a common skin symptom with marked impact on
      quality of life. Adequate treatment can be challenging for clinicians, demanding
      the exploration of new treatment options such as oral antidepressants. OBJECTIVE:
      To evaluate the use of oral antidepressants in chronic pruritus by a systematic
      overview of the available relevant literature. METHODS: The PubMed, EMBASE,
      Cochrane, and Web of Science databases were searched. Studies providing original
      data on the efficacy of oral antidepressants in patients with chronic pruritus
      were included. We assessed the risk for bias by using the Cochrane Risk of Bias
      tool for randomized controlled trials and the Newcastle-Ottawa Scale for
      observational studies. RESULTS: A total of 35 studies evaluating the oral use of
      fluoxetine, fluvoxamine, paroxetine, sertraline, amitriptyline, nortriptyline,
      doxepin, and mirtazapine were included. The majority of included articles showed
      a marked improvement of pruritus during treatment with oral antidepressants.
      LIMITATIONS: Recommendations are mainly based on open-label trials, case series,
      and case reports. CONCLUSION: Oral antidepressants should be considered in
      patients with chronic pruritus that is unresponsive to topical treatment and oral
      antihistamines, particularly in patients with uremic pruritus, cholestatic
      pruritus, or paraneoplastic pruritus. More evidence based on randomized
      controlled trials is required.

PMID- 29033249
TI  - Obesity and risk for incident rosacea in US women.
AB  - BACKGROUND: The relationship between obesity and rosacea is poorly understood.
      OBJECTIVE: To conduct the first cohort study to determine the association between
      obesity and risk for incident rosacea. METHODS: A total of 89,886 participants
      were included from the Nurses' Health Study II (1991-2005). Information on
      history of clinician-diagnosed rosacea and year of diagnosis was collected in
      2005. Information on obesity was collected biennially during follow-up. RESULTS:
      Over 14 years of follow-up, we identified 5249 incident cases of rosacea. The
      risk for rosacea was elevated for those with increased body mass index (BMI,
      Ptrend < .0001). Compared with a BMI of 21.0-22.9 kg/m2, the hazard ratio of
      rosacea was 1.48 (95% confidence interval 1.33-1.64) for BMI >= 35.0. There was a
      trend toward an increased risk for rosacea among participants who had gained
      weight after age 18 years (Ptrend < .0001), with a hazard ratio of 1.04 (95%
      confidence interval 1.03-1.05) per 10-lb weight gain. We also observed
      significantly increased risk for rosacea associated with higher waist
      circumference and hip circumference (Ptrend < .0001), and the associations
      appeared to be independent of BMI. LIMITATIONS: This epidemiologic study did not
      explore underlying mechanisms of the association. CONCLUSIONS: Measures of
      obesity were significantly associated with an increased risk for incident
      rosacea.

PMID- 29033251
TI  - Facilitating electroconvulsive therapy seizure induction: Lower pulse frequency
      or longer stimulus duration?

PMID- 29033252
TI  - Impact of prior ICU experience on ICU patient family members' psychological
      distress: A descriptive study.
AB  - OBJECTIVE: To determine if current levels of anxiety, depression and acute stress
      disorder symptoms differ significantly among family members of intensive-care
      unit patients depending upon previous intensive-care experience. RESEARCH DESIGN:
      This study used a prospective, descriptive study design. SETTING: Family members
      (N=127) from patients admitted within a 72-hour timeframe to the medical,
      surgical, cardiac and neurological intensive care units were recruited from
      waiting rooms at a medium-sized community hospital in the Southeastern United
      States. MAIN OUTCOME MEASURES: Participants completed the Hospital Anxiety and
      Depression Scale, the Impact of Events Scale-Revised, the Acute Stress Disorder
      Scale and a demographic questionnaire. RESULTS: A multivariate analysis revealed
      that family members of intensive-care-unit patients with a prior intensive-care
      experience within the past two years (n=56) were significantly more likely to
      report anxiety, depression and acute stress symptoms, Lambda=0.92, F [4122]=2.70,
      p=0.034, partial eta2=0.08, observed power=0.74. CONCLUSION: Results of this
      study show that family members' psychological distress is higher with previous
      familial or personal intensive-care experience. Nurses need to assess for
      psychological distress in ICU family members and identify those who could benefit
      from additional support services provided in collaboration with multidisciplinary
      support professionals.

PMID- 29033250
TI  - Propionyl-CoA carboxylase - A review.
AB  - Propionyl-CoA carboxylase (PCC) is the enzyme which catalyzes the carboxylation
      of propionyl-CoA to methylmalonyl-CoA and is encoded by the genes PCCA and PCCB
      to form a hetero-dodecamer. Dysfunction of PCC leads to the inherited metabolic
      disorder propionic acidemia, which can result in an affected individual
      presenting with metabolic acidosis, hyperammonemia, lethargy, vomiting and
      sometimes coma and death if not treated. Individuals with propionic acidemia also
      have a number of long term complications resulting from the dysfunction of the
      PCC enzyme. Here we present an overview of the current knowledge about the
      structure and function of PCC. We review an updated list of human variants which
      are published and provide an overview of the disease.

PMID- 29033255
TI  - How Do Voice Perceptual Changes Predict Acoustic Parameters in Persian Voice
      Patients?
AB  - INTRODUCTION: Perceptual and acoustic analyses are essential tools that help
      voice therapists comprehensively assess voice quality. While perceptual
      evaluations are subjective and are influenced by external and culturally driven
      factors, acoustic analysis is an objective and reliable means of evaluating
      voice. The goals of this study were (1) to determine which acoustic parameters
      were predicted by perceptual voice quality and (2) to assess the effect of a
      short period of training on the reliability of perceptual voice analyses for
      Persian speakers. METHOD: This was a cross-sectional study. Subjects were 20
      patients with various voice disorders. Voice samples were obtained during text
      reading and /a/ prolongation. Fifteen expert voice clinicians completed
      perceptual evaluations on voice samples using the Grade, Roughness, Breathiness,
      Asthenia, and Strain scale. We repeated this process after a short period of
      perceptual voice evaluation training. Acoustic analysis was completed using the
      Praat program. We used the intraclass correlation coefficient (ICC) for
      reliability measurement of the perceptual evaluation results and ordinal
      regression procedures to analyze all data. Significance level was set at P <
      0.05. RESULTS: Both intrarater and interrater reliability increased after
      training, for all five parameters. The ICC for grade increased to 0.95 after
      training. Grade and roughness significantly predicted fundamental frequency (F0)
      (P = 0.021 and P = 0.030, respectively) and harmonic-to-noise ratio (HNR) (P =
      0.019 and P = 0.016, respectively). Breathiness significantly predicted shimmer
      (P = 0.013). CONCLUSION: Training had a positive effect and increased the
      reliability of perceptual voice evaluation. For Persian listeners, changes in F0,
      increases in HNR, and shimmer were perceptually associated with poor voice
      quality.

PMID- 29033253
TI  - Multi-criterial patient positioning based on dose recalculation on scatter
      corrected CBCT images.
AB  - BACKGROUND AND PURPOSE: Our aim was to evaluate the feasibility and potential
      advantages of dose guided patient positioning based on dose recalculation on
      scatter corrected cone beam computed tomography (CBCT) image data. MATERIAL AND
      METHODS: A scatter correction approach has been employed to enable dose
      calculations on CBCT images. A recently proposed tool for interactive
      multicriterial dose-guided patient positioning which uses interpolation between
      pre-calculated sample doses has been utilized. The workflow was retrospectively
      evaluated for two head and neck patients with a total of 39 CBCTs. Dose-volume
      histogram (DVH) parameters were compared to rigid image registration based
      isocenter corrections (clinical scenario). RESULTS: The accuracy of the dose
      interpolation was found sufficient, facilitating the implementation of dose
      guided patient positioning. Compared to the clinical scenario, the mean dose to
      the parotid glands could be improved for 2 out of 5 fractions for the first
      patient while other parameters were preserved. For the second patient, the mean
      coverage over all fractions of the high dose PTV could be improved by 4%. For
      this patient, coverage improvements had to be traded against organ at risk (OAR)
      doses within their clinical tolerance limits. CONCLUSIONS: Dose guided patient
      positioning using in-room CBCT data is feasible and offers increased control over
      target coverage and doses to OARs.

PMID- 29033254
TI  - Nodal areas of potential geographic error in adjuvant radiotherapy for biliary
      tract cancer.
AB  - PURPOSE: To determine the areas of potential geographic error in adjuvant
      radiotherapy (RT) for biliary-tract cancer (BTC) by comparing pathological
      surgical data on the pattern of nodal spread with the extent of elective nodal
      CTV used in published RT studies in this setting. MATERIAL/METHODS: A literature
      search was performed to select articles on: 1/adjuvant RT for BTC, that provided
      information on the lymph node stations (LNS) included in the CTV; 2/the
      pathological-surgical data on the patterns of nodal involvement/recurrence in
      BTC. Risk of nodal involvement/recurrence and frequency of inclusion in the CTV
      in RT studies for each of the LNS were compared to determine the areas of
      potential geographic misses and unnecessary irradiation, separately for
      intrahepatic cholangiocarcinoma (IHC), extrahepatic cholangiocarcinoma (EHC) and
      gallbladder-cancer (GBC). RESULTS: Areas of potential geographic misses include:
      for right IHC: paraaortic and superior mesenteric artery (SMA) LNS; for left or
      hilar IHC: left gastric, lesser gastric curvature, paraaortic, and SMA LNS; for
      proximal EHC: paraaortic LNS; for middle EHC: paraaortic and SMA LNS; for distal
      EHC: paraaortic, SMA, and anterior pancreatico-duodenal LNS; for GBC: paraaortic,
      SMA, and posterior pancreatico-duodenal LNS. Celiac-LNS is unnecessarily
      irradiated for middle/distal EHC. CONCLUSIONS: In view of discrepancies between
      pathological-surgical data and the CTVs used in common practice, there is an
      obvious need for international consensus guidelines.

PMID- 29033256
TI  - Acoustic Analysis of Normal Voice Patterns in Pakistani Adults.
AB  - This study was designed to find out normative acoustic measures of adults in
      Pakistan. Age and gender differences in these parameters were also studied. The
      study variables include fundamental frequency, absolute jitter, relative jitter,
      relative average perturbation, 5-point period perturbation quotient perturbation
      quotient, jitter average absolute difference between consecutive periods, divided
      by the average period, shimmer local, shimmer decibel, three-point amplitude
      perturbation quotient, five-point amplitude perturbation quotient, average
      absolute difference of consecutive differences between the consecutive periods'
      amplitudes, and harmonics-to-noise ratio. Participants (N = 71; men = 34; women =
      37) were recruited through two-stage sampling; convenience and purposive
      sampling. Participants were selected from students, staff, and faculty of the
      University of the Punjab, caretakers of the clients coming for clinical services,
      and researchers' friends, family, and acquaintances. Gender groups were further
      divided into three subgroups based on the age bands of 21-30, 31-40, and 41-50
      years. After screening for health issues, the voice samples were recorded in a
      sound-proof acoustic laboratory by using a stand-held microphone and Praat
      software. Praat was also used for voice analyses. Means and standard deviations
      were conducted for the participants. Age and gender differences were investigated
      by using the two-way analysis of variance. Normative values were also measured
      for men and women between the age bracket of 21 and 50 years. Age differences
      were not significant for any variable. Gender differences were significant in
      fundamental frequency, absolute jitter, relative jitter, jitter period
      perturbation quotient, shimmer five-point amplitude perturbation quotient, and
      harmonics-to-noise ratio. The interaction between age and gender was significant
      in all the jitter measures. The interaction showed an increase in all these
      measures between the ages of 31 and 40 years and a decrease between the ages of
      41 and 50 years in women, whereas men showed a reverse effect both in the age
      ranges of 31-40 and 41-50 years.

PMID- 29033257
TI  - Chromogranin A is not a biomarker of mastocytosis.

PMID- 29033258
TI  - Persistent tryptase elevation in a patient with Gaucher disease.

PMID- 29033259
TI  - Comment on: evaluating the feasibility of phrenoesophagopexy during hiatal hernia
      repair in sleeve gastrectomy patients.

PMID- 29033260
TI  - Predicting microRNA biological functions based on genes discriminant analysis.
AB  - Although thousands of microRNAs (miRNAs) have been identified in recent
      experimental efforts, it remains a challenge to explore their specific biological
      functions through molecular biological experiments. Since those members from same
      family share same or similar biological functions, classifying new miRNAs into
      their corresponding families will be helpful for their further functional
      analysis. In this study, we initially built a vector space by characterizing the
      features from miRNA sequences and structures according to their miRBase family
      organizations. Then we further assigned miRNAs into its specific miRNA families
      by developing a novel genes discriminant analysis (GDA) approach in this study.
      As can be seen from the results of new families from GDA, in each of these new
      families, there was a high degree of similarity among all members of nucleotide
      sequences. At the same time, we employed 10-fold cross-validation machine
      learning to achieve the accuracy rates of 68.68%, 80.74%, and 83.65% respectively
      for the original miRNA families with no less than two, three, and four members.
      The encouraging results suggested that the proposed GDA could not only provide a
      support in identifying new miRNAs' families, but also contributing to predicting
      their biological functions.

PMID- 29033261
TI  - Erratum to 'Limitations and opportunities for immune checkpoint inhibitors in
      pediatric malignancies' [Cancer Treat. Rev. 58C (2017) 22-33].

PMID- 29033262
TI  - Primary stability of different plate positions and the role of bone substitute in
      open wedge high tibial osteotomy.
AB  - BACKGROUND: The purpose of this study was to compare the mechanical fixation
      strengths of anteromedial and medial plate positions in osteotomy, and clarify
      the effects of bone substitute placement into the osteotomy site. METHODS: Twenty
      eight sawbone tibia models were used. Four different models were prepared: Group
      A, the osteotomy site was open and the plate position was anteromedial; Group B,
      bone substitutes were inserted into the osteotomy site and the plate position was
      anteromedial; Group C, the osteotomy site was open and the plate position was
      medial; and Group D, bone substitutes were inserted into the osteotomy site and
      the plate position was medial. The loading condition ranged from 0 to 800N and
      one hertz cycles were applied. Changes of the tibial posterior slope angle (TPS),
      stress on the plate and lateral hinge were measured. RESULTS: The changes in the
      TPS and the stress on the plate were significantly larger in Group A than in
      Group C. These were significantly larger in Group A than in Group B, and in Group
      C than in Group D. There was no significant difference between Group B and Group
      D, and no significant difference between knee flexion angles of 0 degrees  and 10
      degrees . Stress on the lateral hinge was significantly smaller when bone
      substitute was used. CONCLUSIONS: A medial plate position was biomechanically
      superior to an anteromedial position if bone substitute was not used. Bone
      substitute distributed the stress concentration around the osteotomy gap and
      prevented an increase in TPS angle regardless of the plate position.

PMID- 29033263
TI  - Persistent extra-axial post-surgical collections and Propionibacterium acnes
      infection. Presentation of two cases and literature review.
AB  - OBJECTIVES: It is common to observe the persistence of extra-axial collections
      after craniotomies. Most of these disappear in weeks or months but some remain.
      The onset of focal symptoms or the growth of these persistent collections months
      or years after surgery may indicate the presence of a chronic and latent
      infection by germs of low virulence such as Propionibacterium acnes (P. acnes).
      METHODS: We present two clinical cases with persistent extra-axial collections,
      which required surgery years after diagnosis, in which P. acnes was isolated as
      an aetiological agent and we reviewed the literature published in this regard.
      RESULTS: These are two patients who, following surgical procedures (decompressive
      craniectomy for severe TBI and craniotomy for right parietal meningioma) and
      extra-axial collections were kept, which were monitored over time and then were
      infected and required emergency evacuation. In these collections P. acnes grew as
      a causal agent and required targeted antibiotics. CONCLUSIONS: We must consider
      P. acnes as an infectious agent of post-surgical collections of long evolution.
      Atypical presentation and radiological changes may be helpful in diagnosis.

PMID- 29033264
TI  - Editor's Note.

PMID- 29033265
TI  - Universal coverage for palliative care in respiratory disease and critical care.

PMID- 29033266
TI  - Mortality from chronic respiratory diseases varies widely in USA.

PMID- 29033267
TI  - Palliative care in interstitial lung disease: living well.
AB  - Progressive fibrotic interstitial lung diseases (ILDs) are characterised by major
      reductions in quality of life and survival and have similarities to certain
      malignancies. However, palliative care expertise is conspicuously inaccessible to
      many patients with ILD. Unmet patient and caregiver needs include effective
      pharmacological and psychosocial interventions to improve quality of life
      throughout the disease course, sensitive advanced care planning, and timely
      patient-centred end-of-life care. The incorrect perception that palliative care
      is synonymous with end-of-life care, with no role earlier in the course of ILD,
      has created a culture of neglect. Interventions that aim to improve life
      expectancy are often prioritised without rigorous assessment of the individual's
      health and psychosocial needs, thereby inadvertently reducing quality of life. As
      in malignant disorders, radical interventions to slow disease progression and
      palliative measures to improve quality of life should both be prioritised.
      Efficient patient-centred models of palliative care must be validated, taking
      into account religious and cultural differences, as well as variability of
      resources. Effective implementation of palliative care for ILD will require
      multidisciplinary participation from clinicians, specialist nurses,
      psychologists, social workers, and, in some countries, non-governmental faith and
      community-based organisations with access to palliative care expertise.

PMID- 29033268
TI  - Aiming for zero tuberculosis transmission in low-burden countries.

PMID- 29033269
TI  - Outcomes of functional treatment versus open reduction and internal fixation of
      condylar mandibular fracture with articular impact: A retrospective study of 83
      adults.
AB  - INTRODUCTION: The treatment of fractures in the mandibular condylar process
      remains controversial. The aim of this study was to assess the outcomes of
      isolated functional treatment versus open reduction and internal fixation (ORIF)
      of mandibular condylar fracture with articular impact based on clinical and
      radiological criteria. MATERIALS AND METHODS: Eighty-three patients with a
      mandibular condylar fracture with articular impact were included in this
      retrospective study. They were divided according to Loukota, Spiessl and Schroll,
      Mercier and Rasse, Neff, and Hlawitschka classifications. Two groups were
      created: operated patients (operated) and non-operated patients (non-operated).
      Occlusal and functional features were evaluated using clinical measurements at 1,
      3, 6, and 12 months after the treatment as well as radiological measurements
      performed preoperatively, 6 weeks later, and at the end of the follow-up.
      RESULTS: A male predominance was observed in the data (69.9%, P<0.0001). Isolated
      functional treatment was applied in 55 patients (66.26%). Twenty-eight patients
      (33.7%) were operated upon using a pre-auricular or modified Risdon's approach.
      Maximal mouth opening (MMO) was lesser in "operated" group compared to "non
      operated" group until 6 months (25.75mm vs 31.96mm, 34.76mm vs 37.95mm, 38.06mm
      vs 41.87mm respectively 1, 3 and, 6 months, P<0.05). Results were satisfactory 1
      year after treatment (41.29mm vs 45.22mm, P>0.05). There was no difference
      concerning temporo-mandibular joint dysfunctions between operated and non
      operated patients. For unilateral fractures, the loss of height of the ramus was
      significantly higher in operated patients initially compared to "non-operated"
      group (P=0.0137). After surgical correction, there was no difference between the
      two sides of mandible. At the end of the follow-up, the there was no difference
      between operated and non-operated ramus (P=0.1304 and 0.6420). CONCLUSION: The
      present study showed that a properly followed isolated functional treatment
      provided similar clinical results to ORIF for mandibular condylar fractures with
      articular impact. Surgical treatment should be preferred when the loss of height
      of the ramus is severe to restore the ramus height since adult condylar
      remodeling is less efficient than in children.

PMID- 29033270
TI  - A survey of contact lens-related complications in a tertiary hospital in China.
AB  - PURPOSE: To describe the type of complications related to contact lens (CL) wear
      in a tertiary hospital in XX, China. METHODS: A retrospective study of 141
      patients who complained discomfort after wearing contact lens on an outpatient
      basis of XX Hospital were conducted from the January 2012 to December 2015. The
      data included patients' demographics, lens type, history, slit-lamp examination,
      reports of corneal scrapings, culture, and examination of in vivo confocal
      microscopy. Binary logistic regression was used to analyse the possible factors
      which were associated with more severe corneal complications and superficial
      punctuate keratitis (SPK). RESULTS: About 86.52% were female and 13.48% were
      male, the age varied between 12 and 56 years old. Of the 141 patients, 82.27%
      were soft CL wearers, 2.84% were rigid gas permeable lens (RGP) wearers, and
      14.89% patients used overnight orthokeratology. The most common complication was
      dry eye (36.88%), followed by SPK (36.17%) during these cases. Blepharitis and
      meibomian gland dysfunction (MGD) were noted in 31.91% of cases. Microbial
      keratitis was seen in 15 patients including 7 cases of Acanthamoeba keratitis.
      Age was a significant factor to be a case of corneal infection or inflammation
      [Exp (B)was 0.918, p=0.030], MGD and blepharitis was found to be significantly
      associated with being a case of SPK [Exp(B)was2.276, p=0.047]. CONCLUSIONS: The
      commonest complication was dry eye in this study, followed by SPK. Lid margin and
      meibomain gland should be paid attention to before contact lens prescription.
      Younger CL wearers need follow-up examinations.

PMID- 29033271
TI  - Surgical Education Module Improves Operative Proficiency in Endoscopic Carpal
      Tunnel Release: A Blinded Randomized Controlled Trial of Trainees.
AB  - OBJECTIVE: The purpose of this study is to evaluate whether an interactive
      endoscopic carpal tunnel release (ECTR) surgical education module can improve
      knowledge of surgical indications and improve procedural competency. DESIGN: An
      ECTR education module was developed and trainees at various level of training
      were enrolled and randomized to surgical module and nonmodule (control) groups.
      Subjects were instructed that they would be the primary surgeon performing an
      ECTR. A written assessment was administered before and after module completion or
      independent case preparation to test comprehension of the procedure. The senior
      author evaluated each subject's intraoperative performance using a 5-point
      scoring system. Statistical analysis was performed using chi-square and paired t
      tests. SETTING: This study took place at a tertiary care hospital at the
      University of Wisconsin. RESULTS: In all, 30 subjects were tested (15 surgical
      module and 15 nonmodule). There were no differences in prepreparation test scores
      between groups. Postpreparation test scores following use of the module were
      significantly higher compared to the nonmodule group. The average operation
      performance scores for the surgical module group and nonmodule group were 96% and
      82%, respectively. The surgical module group performed significantly better on
      all operative steps except for dressing application. Surgical module subjects
      without prior ECTR experience (n = 7) had operative scores that were
      significantly higher than those for nonmodule subjects without previous ECTR
      experience (n = 8) (95% vs. 75%). There was no difference in operative scores
      between surgical module subjects with no prior experience (n = 7) and nonmodule
      subjects who had performed at least 1 prior case (n = 7) (95% vs. 89%).
      CONCLUSIONS: The use of an ECTR surgical education module demonstrates a
      significant benefit in ECTR-naive subjects. When compared to subjects with
      previous ECTR experience, ECTR-naive subjects trained using the surgical module
      demonstrate better familiarity with the equipment and equivalent performance of
      the procedure.

PMID- 29033272
TI  - Graduating Surgical Residents Lack Competence in Critical Care Ultrasound.
AB  - OBJECTIVE: Ultrasound provides accessible imaging for bedside diagnostics and
      procedural guidance, but may lead to misdiagnosis in untrained users. The main
      objective of this study was to determine observed and self-perceived competence
      with critical care ultrasound in graduated general surgery residents. DESIGN: The
      design of this study was a retrospective review. Ultrasound training program
      records were reviewed for number of prior ultrasound examinations performed, self
      perceived competence, observed competence on faculty examinations, and intended
      future use of individual critical care ultrasound examinations. SETTING: This
      study was undertaken at the R Adams Cowley Shock Trauma Center, which is a
      tertiary care center in Baltimore, MD. PARTICIPANTS: Graduated general surgery
      residents were identified at the beginning of their surgical critical care
      fellowship at our institution, and were included if they participated in our
      critical care ultrasound education program. Fifteen graduated general surgery
      residents were included. RESULTS: Prior ultrasound experience ranged from 100%
      for focused assessment of sonography for trauma (FAST) to 13.3% for advanced
      cardiac assessment. Self-perceived competence ranged from 46.7% with FAST to 0%
      for advanced cardiac assessment. Observed competence ranged from 20.0% for FAST
      examinations to 0% for basic cardiac assessment, advanced cardiac assessment, and
      inferior vena cava (IVC) assessment. All participants intended to use ultrasound
      in the future for FAST, pneumothorax detection and basic cardiac assessment, and
      86.7% for IVC assessment and advanced cardiac assessment. Of participants with
      self-perceived competence, 28.6% had observed competence with FAST, 0% with IVC
      assessment, and 100% with pneumothorax detection. CONCLUSIONS: Graduated general
      surgery residents are not competent in multiple critical care ultrasound
      examinations despite universally planning to use critical care ultrasound in
      future practice. Current exposure to ultrasound in residency may give a false
      sense of competency with ultrasound use. A standardized ultrasound curriculum is
      an urgent need for general surgery training.

PMID- 29033273
TI  - Current Techniques of Teaching and Learning in Bariatric Surgical Procedures: A
      Systematic Review.
AB  - OBJECTIVE: The gastric sleeve resection and gastric bypass are the 2 most
      commonly performed bariatric procedures. This article provides an overview of
      current teaching and learning methods of those techniques in resident and fellow
      training. DESIGN: A database search was performed on Pubmed, Embase, and the
      Education Resources Information Center (ERIC) to identify the methods used to
      provide training in bariatric surgery worldwide. After exclusion based on titles
      and abstracts, full texts of the selected articles were assessed. Included
      articles were reviewed using the Grading of Recommendations Assessment,
      Development and Evaluation (GRADE) system. RESULTS: In total, 2442 titles were
      identified and 14 full text articles met inclusion criteria. Four publications
      described an ex vivo training course, and 6 focused on at least 1 step of the
      gastric bypass procedure. Two randomized controlled trials (RCT) provided high
      quality evidence on training aspects. Surgical coaching caused significant
      improvement of Bariatric Objective Structured Assessment of Technical Skills
      (BOSATS) scores (3.60 vs. 3.90, p = 0.017) and reduction of technical errors (18
      vs. 10, p = 0.003). A preoperative warm-up increased global rating scales (GRS)
      scores on depth perception (p = 0.02), bimanual dexterity (p = 0.01), and
      efficiency of movements (p = 0.03). CONCLUSION: Stepwise education, surgical
      coaching, warming up, Internet-based knowledge modules, and ex vivo training
      courses are effective in relation to bariatric surgical training of residents and
      fellows, possibly shortening their learning curves.

PMID- 29033274
TI  - Percutaneous Treatment of Follow-up Lesions After Atrial Switch in Patients With
      Transposition of the Great Arteries.

PMID- 29033275
TI  - Mechanisms of humoral immune response against Pseudomonas aeruginosa biofilm
      infection in cystic fibrosis.
AB  - P. aeruginosa chronic lung infection is the major cause of morbidity and
      mortality in patients with cystic fibrosis (CF), and is characterized by a
      biofilm mode of growth, increased levels of specific IgG antibodies and immune
      complex formation. However, despite being designed to combat this infection, such
      elevated humoral response is not associated with clinical improvement, pointing
      to a lack of anti-pseudomonas effectiveness. The mode of action of specific
      antibodies, as well as their structural features, and even the background
      involving B-cell production, stimulation and differentiation into antibody
      producing cells in the CF airways are poorly understood. Thus, the aim of this
      review is to discuss studies that have addressed the intrinsic features of the
      humoral immune response and provide new insights regarding its insufficiency in
      the CF context.

PMID- 29033276
TI  - Editorial overview: Plant synthetic and systems biology.

PMID- 29033277
TI  - Corrigendum to "22nd International Congress of the World Muscle Society, Saint
      Malo, France, 3rd-7th October 2017" [Neuromuscular Disorders 27S2 (2017) S51
      S270].

PMID- 29033278
TI  - Different profiles of upper limb function in four types of neuromuscular
      disorders.
AB  - The aim of this research was to study impairments, activity limitations and
      participation restrictions due to upper limb involvement in people with four
      different types of neuromuscular disorders (NMD) - FacioScapuloHumeral Dystrophy
      (FSHD), Limb-Girdle Muscular Dystrophy (LGMD), Spinal Muscular Atrophy (SMA) and
      Duchenne Muscular Dystrophy (DMD) - and to investigate whether common or
      different profiles could be identified. Total of 267 respondents with NMD from
      the Netherlands answered a set of questionnaires covering upper limb impairments
      (pain and stiffness), activity limitations and participation restrictions. Pain
      was most often reported by persons with FSHD. Problems in the FSHD group were
      mainly characterized by relatively high scores for pain and stiffness and low
      scores for activity limitations. People with LGMD reported also low scores for
      activity limitations. Conversely, people with SMA and DMD experienced in general
      relatively low scores for pain and stiffness and high scores for activity
      limitations. Although people with FSHD and LGMD had relatively few activity
      limitations, all NMD groups experienced restrictions when participating in social
      activities. Our results indicate specific profiles of upper limb function in
      different types of NMD. While the profile observed in persons with FSHD seems to
      reflect overuse, the profile seen in persons with DMD and SMA is suspicious of
      disuse, each requiring a specific rehabilitation strategy.

PMID- 29033279
TI  - Guided self-help cognitive-behaviour Intervention for VoicEs (GiVE): Results from
      a pilot randomised controlled trial in a transdiagnostic sample.
AB  - BACKGROUND: Few patients have access to cognitive behaviour therapy for psychosis
      (CBTp) even though at least 16 sessions of CBTp is recommended in treatment
      guidelines. Briefer CBTp could improve access as the same number of therapists
      could see more patients. In addition, focusing on single psychotic symptoms, such
      as auditory hallucinations ('voices'), rather than on psychosis more broadly, may
      yield greater benefits. METHOD: This pilot RCT recruited 28 participants (with a
      range of diagnoses) from NHS mental health services who were distressed by
      hearing voices. The study compared an 8-session guided self-help CBT intervention
      for distressing voices with a wait-list control. Data were collected at baseline
      and at 12weeks with post-therapy assessments conducted blind to allocation. Voice
      impact was the pre-determined primary outcome. Secondary outcomes were
      depression, anxiety, wellbeing and recovery. Mechanism measures were self-esteem,
      beliefs about self, beliefs about voices and voice-relating. RESULTS: Recruitment
      and retention was feasible with low study (3.6%) and therapy (14.3%) dropout.
      There were large, statistically significant between-group effects on the primary
      outcome of voice-impact (d=1.78; 95% CIs: 0.86-2.70), which exceeded the minimum
      clinically important difference. Large, statistically significant effects were
      found on a number of secondary and mechanism measures. CONCLUSIONS: Large effects
      on the pre-determined primary outcome of voice-impact are encouraging, and
      criteria for progressing to a definitive trial are met. Significant between-group
      effects on measures of self-esteem, negative beliefs about self and beliefs about
      voice omnipotence are consistent with these being mechanisms of change and this
      requires testing in a future trial.

PMID- 29033280
TI  - The contribution of the contingent negative variation (CNV) to goal maintenance.
AB  - The dot pattern expectancy (DPX) task has been strongly recommended as a measure
      of goal maintenance, which is impaired in schizophrenia patients. The current
      event-related potential (ERP) study was designed mainly to identify the ERP
      component that could represent the goal maintenance process of the DPX task as
      indexed by the error rate of the BX vs. AY (EBX-AY). We focused our analysis on
      the cue-phased contingent negative variation (CNV) and found a significant
      association between the EBX-AY and the amplitude of the difference wave of cue B
      vs. cue A (CNVB-A) (for CP3, beta=-0.262, P=0.001; for CPZ, beta=-0.184, P=0.025;
      for CP4, beta=-0.201, P=0.015). Lower EBX-AY (better goal maintenance) was
      correlated with larger CNVB-A. Further analysis found a significant association
      between the error rate of AY condition (EAY) and the amplitude of CNVA (for CP3,
      beta=-0.180, P=0.029; for CPZ, beta=-0.184, P=0.024; for CP4, beta=-0.208,
      P=0.011) and a significant association between the error rate of BX condition
      (EBX) and the amplitude of CNVB-A (for CP3, beta=-0.198, P=0.016; for CPZ, beta=
      0.165, P=0.043; for CP4, beta=-0.151, P=0.066), but not the amplitude of the CNVB
      (all P>0.05). All these results together suggested that the cue-phased CNV could
      be used to represent the goal maintenance process. Future research needs to
      verify these results with schizophrenia patients.

PMID- 29033281
TI  - Sedentary behaviour, physical activity, cardiorespiratory fitness and
      cardiometabolic risk in psychosis: The PsychiActive project.
AB  - This study aimed to explore the possible independent associations of sedentary
      behaviour (SB), physical activity (PA), and cardiorespiratory fitness (CRF) with
      clustered (CCRS) and individual cardiometabolic risk (waist circumference
      [waist], systolic/diastolic blood pressure, triglycerides, high-density
      lipoprotein-cholesterol, and fasting blood glucose) in patients with psychosis.
      In 43 outpatients with psychosis (mean age+/-SD: 42.3+/-8.5years, 86% men), SB
      and light, moderate-to-vigorous, and total PA were measured with the SenseWear
      Pro3 Armband, and CRF with the 6-minute walking test. Multiple linear regression
      models adjusted for multiple confounders were applied. High SB, low PA and low
      CRF levels were associated with an unfavourable cardiometabolic risk profile
      (increased presence of metabolic syndrome and number of cardiometabolic
      abnormalities, as well as worse values and elevated presence of abnormalities for
      all individual cardiometabolic risk factors). SB was associated with CCRS, number
      of cardiometabolic abnormalities, waist, and fasting blood glucose (all p<0.05).
      After adjusting for PA and CRF, waist and fasting blood glucose remained
      significant. Light PA was associated with waist, moderate-to-vigorous PA with
      CCRS, and total PA with CCRS and waist (all p<0.05). These results became non
      significant after adjusting for SB and CRF. CRF was associated with CCRS, waist,
      and systolic blood pressure (all p<0.05). The associations with CCRS and waist
      remained significant after adjusting for SB and PA. Together, these results
      suggest the importance of considering SB and CRF, regardless PA, in the
      prevention and treatment of cardiometabolic disorders among patients with
      psychosis.

PMID- 29033282
TI  - Character strengths of individuals with first episode psychosis in Individual
      Resiliency Training.
AB  - Positive psychology interventions that integrate a person's strengths into
      treatment result in improvements in life satisfaction and well-being. Character
      strengths classified within six core virtues (wisdom/knowledge, courage,
      humanity, justice, temperance, and transcendence) have been the subject of
      substantial research. Though a number of studies have been conducted in the
      general population, little is known about the character strengths of individuals
      with first episode psychosis (FEP). Moreover, positive psychology principles, in
      particular a focus on personal strengths, have been increasingly integrated into
      FEP treatment and was a core component of Individual Resiliency Training (IRT),
      the individual therapy component of NAVIGATE tested in the Recovery After an
      Initial Schizophrenia Episode Early Treatment Program. As such, the present study
      offers an examination of character strengths among 105 FEP clients in specialized
      early intervention treatment. The present study included two primary aims: 1) to
      conduct a descriptive analysis of character strengths of FEP individuals and 2)
      to examine exploratory associations between character strengths and changes in
      symptomatic and recovery variables over six months. Results revealed that the
      most commonly identified strengths were: Honesty, Authenticity, and Genuineness
      (40.95%), Kindness and generosity (37.14%), Fairness, equity, and justice
      (29.52%), Gratitude (29.52%), and Humor and playfulness (29.52%). Three virtues
      (Humanity, Justice, and Transcendence) were significantly associated with
      improvements in symptoms, psychological well-being, and interpersonal relations
      over six months. Overall, the present study offers a glimpse into how persons
      with FEP view their strengths and how certain clusters of strengths are related
      to important outcomes.

PMID- 29033284
TI  - Comments on "Therapy with mesenchymal stromal cells or conditioned medium reverse
      cardiac alterations in a high-fat diet-induced obesity model".

PMID- 29033283
TI  - Developmental trajectory of mismatch negativity and visual event-related
      potentials in healthy controls: Implications for neurodevelopmental vs.
      neurodegenerative models of schizophrenia.
AB  - Sensory processing deficits are core features of schizophrenia, reflected in
      impaired generation of event-related potential (ERP) measures such as auditory
      mismatch negativity (MMN) and visual P1. To understand the potential time course
      of development of deficits in schizophrenia, we obtained MMN to unattended
      duration, intensity and frequency deviants, and visual P1 to attended LSF
      stimuli, in 43 healthy individuals ages 6 to 25years (mean 17), and compared
      results to data from 30 adult schizophrenia patients (mean age 38). We analyzed
      "time-domain" measures of amplitude and latency, and event-related spectral
      perturbation (ERSP, "time-frequency") to evaluate underlying neurophysiological
      mechanisms. Duration and intensity MMN amplitudes increased from childhood to
      late adolescence, while frequency MMN reached maximum amplitude during early
      development. As reported previously, in ERSP analyses, MMN activity corresponded
      primarily to theta-band (4-7Hz) activity, while responses to standards occurred
      primarily in alpha (8-12Hz) across age groups. Both deviant-induced theta and
      standard-induced alpha activity declined significantly with age for all deviant
      types. Likewise, visual P1 also showed an amplitude decline over development,
      reflecting a reduction in both evoked power and ITC. While MMN "difference"
      waveform ERP data suggest failure of maturation in schizophrenia, MMN ERSP
      analyses instead support a neurodegenerative process, as these isolate responses
      to deviants and standards, showing large low-frequency evoked power for both in
      children. Neurodegenerative processes are also supported by large visual P1
      amplitudes and large low-frequency evoked power in children, in contrast with
      adult schizophrenia. Sensory processing deficits in schizophrenia may be related
      to accelerated synaptic pruning.

PMID- 29033285
TI  - Antibiotic prophylaxis in breast reduction surgery: A different approach.

PMID- 29033286
TI  - Botulinum Toxins A and E Inflict Dynamic Destabilization on t-SNARE to Impair
      SNARE Assembly and Membrane Fusion.
AB  - Botulinum toxins (BoNTs) A and E block neurotransmitter release by specifically
      cleaving the C- terminal ends of SNAP-25, a plasma membrane SNARE protein. Here,
      we find that SNAP-25A and E, the cleavage products of BoNT A and E, respectively,
      terminate membrane fusion via completely different mechanisms. Combined studies
      of single-molecule FRET and single-vesicle fusion assays reveal that SNAP-25E is
      incapable of supporting SNARE pairing and thus, vesicle docking. In contrast,
      SNAP-25A facilitates robust SNARE pairing and vesicle docking with somewhat
      reduced SNARE zippering, which leads to severe impairment of fusion pore opening.
      The electron paramagnetic resonance results show that the discrepancy between
      SNAP-25A and E might stem from the extent of the dynamic destabilization of the t
      SNARE core at the N-terminal half, which plays a pivotal role in nucleating SNARE
      complex formation. Thus, the results provide insights into the structure/dynamics
      based mechanism by which BoNT A and E impair membrane fusion.

PMID- 29033287
TI  - Rotamer Libraries for the High-Resolution Design of beta-Amino Acid Foldamers.
AB  - beta-Amino acids offer attractive opportunities to develop biologically active
      peptidomimetics, either employed alone or in conjunction with natural alpha-amino
      acids. Owing to their potential for unique conformational preferences that
      deviate considerably from alpha-peptide geometries, beta-amino acids greatly
      expand the possible chemistries and physical properties available to polyamide
      foldamers. Complete in silico support for designing new molecules incorporating
      non-natural amino acids typically requires representing their side-chain
      conformations as sets of discrete rotamers for model refinement and sequence
      optimization. Such rotamer libraries are key components of several state-of-the
      art design frameworks. Here we report the development, incorporation in to the
      Rosetta macromolecular modeling suite, and validation of rotamer libraries for
      beta3-amino acids.

PMID- 29033290
TI  - Nonvascularized Cartilage Grafts Versus Vascularized Cartilage Flaps: Comparison
      of Cartilage Quality 6 Months After Transfer.
AB  - PURPOSE: Subchondral perfusion of osteochondral grafts has been shown to be
      important in preventing long-term cartilage degeneration. In carpal
      reconstruction, subchondral perfusion from the graft bed is limited. This study's
      purpose was to compare the histological characteristics of cartilage in
      osteochondral grafts supported by synovial imbibition alone to cartilage of
      vascularized osteochondral flaps that have both synovial and vascular pedicle
      perfusion. METHODS: Two adjacent osteochondral segments were harvested on the
      medial femoral trochlea in domestic 6- to 8-month-old pigs. Each segment measured
      approximately 12 mm * 15 mm * 17 mm. One segment was maintained on the descending
      geniculate artery vascular pedicle. The adjacent segment was separated from the
      pedicle to serve as a nonvascularized graft. A thin layer of methylmethacrylate
      cement was used to line the harvest site defect to prevent vascular ingrowth to
      the subsequently replaced specimens. The pigs were maintained on a high-calorie
      feed and returned to ambulation and full weight-bearing on the surgical legs. The
      animals were sacrificed after 6 months and the specimens were reharvested,
      sectioned, and examined. The cartilage was graded by 2 pathologists blinded to
      the origin of specimens as vascularized flaps or nonvascularized grafts. RESULTS:
      All specimens were assigned scores utilizing the International Cartilage Repair
      Society grading system. Scoring for chondrocyte viability, cartilage surface
      morphology, and cell and matrix appearance was significantly higher in the
      vascularized osteochondral group than in the graft group. CONCLUSIONS: When
      deprived of subchondral perfusion from underlying bone, osteochondral
      vascularized flaps in an intrasynovial environment demonstrate superior cartilage
      quality and survival compared with nonvascularized grafts. CLINICAL RELEVANCE: In
      locations in which perfusion from surrounding bone may be limited (ie, proximal
      scaphoid or proximal lunate reconstruction), articular reconstruction using
      vascularized osteochondral flaps will yield superior cartilage organization and
      architecture than nonvascularized osteochondral grafts. The clinical and
      functional relevance of this finding requires further study.

PMID- 29033288
TI  - The Therapeutic Antibody LM609 Selectively Inhibits Ligand Binding to Human
      alphaVbeta3 Integrin via Steric Hindrance.
AB  - The LM609 antibody specifically recognizes alphaVbeta3 integrin and inhibits
      angiogenesis, bone resorption, and viral infections in an arginine-glycine
      aspartate-independent manner. LM609 entered phase II clinical trials for the
      treatment of several cancers and was also used for alphaVbeta3-targeted
      radioimmunotherapy. To elucidate the mechanisms of recognition and inhibition of
      alphaVbeta3 integrin, we solved the structure of the LM609 antigen-binding
      fragment by X-ray crystallography and determined its binding affinity for
      alphaVbeta3. Using single-particle electron microscopy, we show that LM609 binds
      at the interface between the beta-propeller domain of the alphaV chain and the
      betaI domain of the beta3 chain, near the RGD-binding site, of all observed
      integrin conformational states. Integrating these data with fluorescence size
      exclusion chromatography, we demonstrate that LM609 sterically hinders access of
      large ligands to the RGD-binding pocket, without obstructing it. This work
      provides a structural framework to expedite future efforts utilizing LM609 as a
      diagnostic or therapeutic tool.

PMID- 29033289
TI  - Foldability of a Natural De Novo Evolved Protein.
AB  - The de novo evolution of protein-coding genes from noncoding DNA is emerging as a
      source of molecular innovation in biology. Studies of random sequence libraries,
      however, suggest that young de novo proteins will not fold into compact, specific
      structures typical of native globular proteins. Here we show that Bsc4, a
      functional, natural de novo protein encoded by a gene that evolved recently from
      noncoding DNA in the yeast S. cerevisiae, folds to a partially specific three
      dimensional structure. Bsc4 forms soluble, compact oligomers with high beta sheet
      content and a hydrophobic core, and undergoes cooperative, reversible
      denaturation. Bsc4 lacks a specific quaternary state, however, existing instead
      as a continuous distribution of oligomer sizes, and binds dyes indicative of
      amyloid oligomers or molten globules. The combination of native-like and non
      native-like properties suggests a rudimentary fold that could potentially act as
      a functional intermediate in the emergence of new folded proteins de novo.

PMID- 29033291
TI  - Controversies in Poland Syndrome: Alternative Diagnoses in Patients With
      Congenital Pectoral Muscle Deficiency.
AB  - PURPOSE: Poland syndrome was first described as a deficiency of the pectoral
      muscle with ipsilateral symbrachydactyly. Currently, numerous case reports
      describe variations of Poland syndrome in which pectoral muscle deficiency is
      often used as the only defining criterion. However, more syndromes can present
      with pectoral muscle deficiency. The aim of this review is to illustrate the
      diversity of the phenotypic spectrum of Poland syndrome and to create more
      awareness for alternative diagnoses in pectoral muscle deficiency. METHODS: A
      systematic literature search was performed. Articles containing phenotypical
      descriptions of Poland syndrome were included. Data extraction included number of
      patients, sex, familial occurrence, and the definition of Poland syndrome used.
      In addition, hand deformities, thoracic deformities, and other deformities in
      each patient were recorded. Alternative syndrome diagnoses were identified in
      patients with a combination of hand, thorax, and other deformities. RESULTS: One
      hundred-and-thirty-six articles were included, describing 627 patients. Ten
      different definitions of Poland syndrome were utilized. In 58% of the cases, an
      upper extremity deformity was found and 43% of the cases had an associated
      deformity. Classic Poland syndrome was seen in 29%. Fifty-seven percent of the
      patients with a pectoral malformation, a hand malformation, and another deformity
      had at least 1feature that matched an alternative syndrome. CONCLUSIONS: Pectoral
      muscle hypoplasia is not distinctive for Poland syndrome alone but is also
      present in syndromes with other associated anomalies with a recognized genetic
      cause. Therefore, in patients with an atypical phenotype, we recommend
      considering other diagnoses and/or syndromes before diagnosing a patient with
      Poland syndrome. This can prevent diagnostic and prognostic errors. CLINICAL
      RELEVANCE: Differentiating Poland syndrome from the alternative diagnoses has
      serious consequences for the patient and their family in terms of inheritance and
      possible related anomalies.

PMID- 29033292
TI  - [Dosimetric verification of MammoSite treatment plans using Monte Carlo
      simulations and measurements with a 2D ionization chamber array].
AB  - The surgical removal of a breast tumour is often followed by postoperative
      irradiation of the surrounding tissue with a radioactive source (brachytherapy).
      When performing the MammoSite procedure, a spherical silicone balloon is inserted
      and filled with a NaCl solution. In a period of about five days in several
      sessions an iridium-192 source with high activity travels through a catheter into
      the balloon (afterloading) to irradiate the tumour cells remaining in the cavity.
      In this study, dose distributions of a MammoSite applicator are investigated
      based on measurements with a 2D detector array, Monte Carlo simulations and
      calculations with BrachyVision. The focus is set on the 2D detector array and its
      possible application in the verification process in 3D brachytherapy treatment
      planning. The measured dose distributions conform well to the doses of
      BrachyVision with deviations of less than 5% within the clinically relevant field
      range. The deviations of the measured and calculated distributions from the
      simulation results are below 3%. The 2D detector array allows a new verification
      method for MammoSite treatment plans with sufficient accuracy. Future
      verifications can be performed without additional Monte Carlo simulations.

PMID- 29033293
TI  - CT and MRI slice separation evaluation by LabView developed software.
AB  - The efficient use of Computed Tomography (CT) and Magnetic Resonance Imaging
      (MRI) equipment necessitates establishing adequate quality-control (QC)
      procedures. In particular, the accuracy of slice separation, during multislices
      acquisition, requires scan exploration of phantoms containing test objects. To
      simplify such procedures, a novel phantom and a computerised LabView-based
      procedure have been devised, enabling determination the midpoint of full width at
      half maximum (FWHM) in real time while the distance from the profile midpoint of
      two progressive images is evaluated and measured. The results were compared with
      those obtained by processing the same phantom images with commercial software. To
      validate the proposed methodology the Fisher test was conducted on the resulting
      data sets. In all cases, there was no statistically significant variation between
      the commercial procedure and the LabView one, which can be used on any CT and MRI
      diagnostic devices.

PMID- 29033295
TI  - Can Multidetector Computed Tomography Rule Out Left Atrial Thrombus in Patients
      With Atrial Fibrillation?

PMID- 29033294
TI  - Acetaminophen or Nonsteroidal Anti-Inflammatory Drugs in Acute Musculoskeletal
      Trauma: A Multicenter, Double-Blind, Randomized, Clinical Trial.
AB  - STUDY OBJECTIVE: We determine whether pain treatment with acetaminophen was not
      inferior to nonsteroidal anti-inflammatory drugs or the combination of both in
      minor musculoskeletal trauma. METHODS: The Paracetamol or NSAIDs in Acute
      Musculoskeletal Trauma Study was a double-blind, randomized, clinical trial
      conducted in 2 general practices and 2 emergency departments in the Netherlands.
      A total of 547 adults, aged 18 years and older, with acute blunt minor
      musculoskeletal extremity trauma were randomly assigned in a 1:1:1 ratio to
      acetaminophen 4,000 mg/day, diclofenac 150 mg/day, or acetaminophen 4,000
      mg/day+diclofenac 150 mg/day during 3 consecutive days. Patients, health care
      staff, and outcome assessors were blinded for treatment allocation. Follow-up for
      each patient was 30 days. Primary outcome measures were between-group differences
      in mean numeric rating scale (NRS) pain scores in rest and with movement at 90
      minutes after initial drug administration compared with baseline pain scores with
      a predefined noninferiority margin of 0.75 NRS points. Secondary outcomes
      included NRS pain scores during 3 consecutive days and need for additional
      analgesia. RESULTS: One hundred eighty-two patients were treated with
      acetaminophen, 183 with diclofenac, and 182 with combination treatment. Intention
      to-treat analysis revealed mean NRS reduction in rest -1.23 (95% confidence
      interval [CI] -1.50 to -0.95) and -1.72 (95% CI -2.01 to -1.44) with movement,
      both for acetaminophen at 90 minutes compared with baseline. Pairwise comparison
      in rest with diclofenac showed a difference of -0.027 (97.5% CI -0.45 to 0.39)
      and -0.052 (97.5% CI -0.46 to 0.36) for combination treatment. With movement,
      these numbers were -0.20 (97.5% CI -0.64 to 0.23) and -0.39 (97.5% CI -0.80 to
      0.018), respectively. All differences were well below the predefined
      noninferiority margin. CONCLUSION: Pain treatment with acetaminophen was not
      inferior to that with diclofenac or the combination of acetaminophen and
      diclofenac in acute minor musculoskeletal extremity trauma, both in rest and with
      movement.

PMID- 29033297
TI  - No Easy Way Out: A Case of Physician-Assisted Dying in the Emergency Department.
AB  - Currently, 1 out of 6 Americans lives within a jurisdiction in which physician
      assisted dying is legally authorized. In most cases, patients ingest lethal
      physician-assisted dying medications at home without involvement of emergency
      medical services (EMS) or the emergency department (ED). However, occasionally
      the dying process is interrupted as a result of incomplete ingestion or vomiting
      of medications, confusion about timing of dying trajectory, familial emotional
      distress, and other variables. A case is presented here of a patient who arrived
      by ambulance to an urban ED after ingesting physician-assisted dying medication.
      Stepwise analysis of communication and actions between providers (paramedics,
      emergency physician, and admitting physician), risk management, and family are
      described chronologically. This case highlights the significant distress
      experienced by each party, as well as key challenges and learning points.
      Guidance is provided to emergency providers about expectations and communication.
      In states with limited physician-assisted dying experience, many EMS agencies,
      EDs, and hospitals require comprehensive protocols to handle the complex ethical
      and psychosocial issues surrounding physician-assisted dying in the ED.

PMID- 29033298
TI  - Passive smoking and Parkinson's disease in California Teachers.
AB  - INTRODUCTION: Tobacco smoking is consistently inversely associated with
      Parkinson's disease (PD) in men and women; recently this has been related to
      reverse causation, prompting questions as to whether similar patterns exist for
      passive smoke exposure. We used baseline and follow-up data from the California
      Teachers Study, a prospective cohort of women, to investigate whether timing,
      location and cumulative measures of intensity and duration of passive smoke
      exposure are associated with PD risk. METHODS: Using a nested case-control
      approach, we included 224 diagnostically validated cases (158 with no history of
      personal smoking) and selected 3230 age- and race-matched controls (1973 with no
      history of personal smoking). We estimated odds ratios(ORs) and 95% confidence
      intervals(CI) by fitting adjusted multivariable unconditional logistic regression
      models. RESULTS: Among lifelong non-smokers, passive smoke exposure combined
      across all settings and accumulated over a lifetime was not associated with PD
      risk (OR = 1.18, 95% CI 0.60, 2.30). Workplace exposure was also not associated
      with risk. Household exposure during adulthood but not childhood was inversely
      associated with PD (OR = 0.59, 95% CI 0.40, 0.87). Exposure to passive smoke in
      other social settings was positively associated with PD (OR = 1.62, 95% CI 1.11,
      2.36). These contradictory results may be attributable to chance due to multiple
      comparisons in subgroup analyses. No pattern emerged to suggest that increasing
      years of passive smoke exposure, smokiness of the setting, or combined smokiness
      by exposure years was associated with lower PD risk. CONCLUSION: Results do not
      convincingly support a protective effect of passive smoking in PD.

PMID- 29033296
TI  - A Comparison of Headache Treatment in the Emergency Department: Prochlorperazine
      Versus Ketamine.
AB  - STUDY OBJECTIVE: Intravenous subdissociative-dose ketamine has been shown to be
      effective for pain management, but has not been specifically studied for
      headaches in the emergency department (ED). For this reason, we designed a study
      to compare standard treatment (prochlorperazine) with ketamine in patients with
      benign headaches in the ED. METHODS: This study was a multicenter, double-blind,
      randomized, controlled trial with a convenience sample of patients presenting to
      the ED with benign headaches. Patients were randomized to receive either
      prochlorperazine and diphenhydramine or ketamine and ondansetron. Patients'
      headache severity was measured on a 100-mm visual analog scale (VAS) at 0, 15,
      30, 45, and 60 minutes. Nausea, vomiting, anxiety, and the need for rescue
      medications were also tracked. Patients were contacted at 24 to 48 hours
      posttreatment to rate their satisfaction and to determine whether they were still
      experiencing a headache. RESULTS: There were a total of 54 subjects enrolled. Two
      patients in the ketamine group and one in the prochlorperazine group withdrew
      because of adverse effects of the medications. In regard to the primary outcome,
      at 60 minutes, the prochlorperazine group had a mean improvement in VAS pain
      scores of 63.5 mm compared with 43.5 mm in the ketamine group, corresponding to a
      between-groups difference of 20.0 mm (95% confidence interval [CI] 2.8 to 37.2
      mm) and a P value of .026. At 45 minutes, the prochlorperazine group had a mean
      improvement in pain scores of 56.1 mm compared with 38.0 mm in the ketamine
      group, a difference of 18.1 mm (95% CI 1.0 to 35.2 mm). At 24- to 48-hour follow
      up, the mean satisfaction score was 8.3 of 10 for prochlorperazine and 4.9 of 10
      for ketamine, a difference of 3.4 (95% CI 1.2 to 5.6). There was not a
      statistically significant difference in the percentage of patients who had a
      headache at follow-up or in other secondary outcomes. CONCLUSION:
      Prochlorperazine appears to be superior to ketamine for the treatment of benign
      headaches in the ED.

PMID- 29033299
TI  - Unpredictable pain timings lead to greater pain when people are highly intolerant
      of uncertainty.
AB  - BACKGROUND AND PURPOSE: Many psychological factors are known to influence pain
      perception. Among them, intolerance of uncertainty (IU) may play a key modulating
      role in situations where uncertainty prevails, especially uncertainty regarding
      the timing of painful events. The objective of this study was to explore the
      impact of individual differences in IU on pain perception during predictable and
      unpredictable stimulation timings. We hypothesized that people with high IU, as
      opposed to those with low IU, would perceive more pain when the timing of painful
      stimulations cannot be predicted, as compared to when they can. METHODS: Twenty
      (20) healthy adults, aged between 18 and 35 years old, were recruited. Painful
      sensations were provoked using transcutaneous electrical stimulations of the
      right sural nerve. By measuring IU (Intolerance of Uncertainty Scale) and
      subjective pain (verbal numerical rating scale), it was possible to test the
      relationship between IU and pain perception, by simulating predictable and
      unpredictable painful experiences. This was done through cued shock interval
      (CSI) blocks, with either variable timing or fixed timings (long or short time
      frame). Self-administered questionnaires were also used to measure pain
      hypervigilance, pain catastrophizing, state anxiety, and trait anxiety. RESULTS:
      Pearson correlations confirmed the presence of an association (r=0.63) between IU
      and the change in pain intensity provoked by unpredictable stimulation timings.
      Importantly, this association was significant only for stimulations provided at
      long CSIs, indicating that higher IU scores predicted higher pain intensity
      scores when stimulation timings became unpredictable, and when the cued delay was
      long. No association was found between pain scores and other psychological
      variables. CONCLUSIONS: Our results show that IU moderately correlates to the
      change in pain intensity provoked by unpredictable stimulation timings. High IU
      scores were associated with a worsening of the subjective pain experience,
      especially during long delays in an unpredictable situation. These observations
      suggest that IU could be considered as a psychological variable that is able to
      influence pain perception in certain situations. IMPLICATIONS: Assessing and
      addressing IU could be an added value in pain-related therapy, especially in
      chronic pain.

PMID- 29033300
TI  - Impact of Synchronous Multiple Primary Malignant Tumors on Newly Diagnosed
      Hematological Malignancies.
AB  - BACKGROUND: Hematological malignancies are occasionally observed with synchronous
      multiple primary malignant tumors (sMPMTs) at diagnosis. We aimed to clarify the
      impact of sMPMTs on newly diagnosed hematological malignancies and determine the
      optimal treatment strategies. PATIENTS AND METHODS: We analyzed the outcomes of
      649 patients with hematological malignancies, including 19 patients with sMPMTs
      (2.9%), and compared the outcomes between patients with and without sMPMTs.
      RESULTS: The overall survival (OS) and disease-free survival (DFS) rates for
      patients with sMPMTs were 77% and 70%, respectively, at 2 years; these rates were
      not statistically different from those for patients without sMPMTs (P = .17 and P
      = .64, respectively). Multivariate analysis showed that the presence of sMPMTs
      was not a significant prognostic factor for OS, DFS, or relapse (hazard ratio
      [HR] 1.48, 95% confidence interval [CI] 0.65-3.38, P = .35; HR 0.97, 95% CI 0.46
      2.10, P = .97; and HR 0.79, 95% CI 0.29-2.14, P = .65). In patients with sMPMTs,
      the order of treatment was not a significant prognostic factor. However,
      discontinuation of treatment was a marginally favorable factor and might reflect
      a selection bias. CONCLUSION: The presence of sMPMTs was not a significant risk
      factor for patients with newly diagnosed hematological malignancies. It is
      important to provide adequate treatment for both hematological malignancies and
      solid tumors at the physician's discretion.

PMID- 29033301
TI  - Characterization of gyrA and gyrB mutations associated with fluoroquinolone
      resistance in Mycobacterium tuberculosis isolates from Morocco.
AB  - OBJECTIVES: Fluoroquinolones (FQs) are the cornerstone of treatment for drug
      resistant tuberculosis (TB). They are the most effective second-line
      antimycobacterial drugs and are recommended for the treatment of multidrug
      resistant TB (MDR-TB). However, it is widely accepted that FQ resistance is high
      among MDR-TB isolates. Thus, characterisation of mutations conferring resistance
      to FQs will be of a great interest for effective and efficient management of TB
      resistance in Morocco. METHODS: A laboratory collection of 30 Mycobacterium
      tuberculosis isolates previously characterised as phenotypically and
      genotypically MDR as well as 20 randomly selected pan-susceptible isolates were
      included in this retrospective study. The mutation profiles associated with
      resistance to FQs were assessed by PCR and DNA sequencing. Target sequences for
      two genes (gyrA and gyrB) were examined. All strains had their fingerprint
      previously established by spoligotyping. RESULTS: Molecular analyses showed that
      30% of the MDR-TB isolates harboured FQ resistance mutations in gyrA, with the
      most prevalent being an alanine to threonine at position 90 (Ala90Thr) (56%;
      5/9). None of the isolates harboured mutations in gyrB. All gyrA resistance
      mutant strains belonged to the LAM lineage, mostly LAM9, raising the possible
      emergence of a specific clone (gyrA mutant/LAM9). CONCLUSION: The results of this
      preliminary study highlight the high prevalence of FQ resistance among MDR-TB
      isolates in Morocco and consequently the need for rapid detection of FQ
      resistance once MDR-TB is confirmed to adjust treatment in a timely manner and to
      interrupt the propagation of more severe forms of M. tuberculosis drug
      resistance.

PMID- 29033302
TI  - Antimicrobial susceptibility of Helicobacter pylori strains isolated from
      children in Israel.
AB  - OBJECTIVES: Helicobacter pylori is a bacterial pathogen causing inflammation of
      the gastric mucosa that may lead to peptic ulcer, perforation or malignancy.
      Children are at risk of contracting H. pylori and developing subsequent
      morbidity. Diagnosis and management in children are difficult and merit a
      different approach compared with adults. This study aimed to describe the
      antimicrobial resistance rates of H. pylori to amoxicillin, tetracycline,
      clarithromycin, metronidazole, levofloxacin and rifampicin. METHODS: Biopsies
      (n=154) collected during endoscopic examinations were cultivated for 10days using
      a growth medium selective for H. pylori, of which 89 were H. pylori-positive.
      Antimicrobial resistance of the strains was assessed by Etest to establish
      minimum inhibitory concentrations (MICs) according to British Society for
      Antimicrobial Chemotherapy guidelines. RESULTS: Resistance rates were most
      notable for amoxicillin and clarithromycin at 12% and 35% with MICs of 0.74MUg/mL
      and 2.51MUg/mL, respectively. Resistance rates to tetracycline and levofloxacin
      were 8% and 2% with MICs of 2.57MUg/mL and 2.0MUg/mL, respectively. Resistance
      rates to rifampicin and metronidazole were 3% and 8% with MICs of 2.0MUg/mL and
      9.71MUg/mL, respectively. CONCLUSION: Current rising antibiotic resistance rates
      for H. pylori are of concern. Performance of culture enables determination of the
      susceptibility profile, which may lead to a better choice of, and perhaps
      narrower spectrum, antibiotic agent. In light of these findings, we suggest that
      optimising the choice of antibiotic agent in children with H. pylori infection
      remains a challenge for clinicians and thus requires further investigation in
      randomised clinical trials.

PMID- 29033303
TI  - Schwann Cells in the Ventral Dermis Do Not Derive from Myf5-Expressing
      Precursors.
AB  - The embryonic origin of lineage precursors of the trunk dermis is somewhat
      controversial. Precursor cells traced by Myf5 and Twist2 (Dermo1) promoter
      activation (i.e., cells of presumed dermomyotomal lineage) have been reported to
      generate Schwann cells. On the other hand, abundant data demonstrate that dermal
      Schwann cells derive from the neural crest. This is relevant because dermal
      precursors give rise to neural lineages, and multilineage differentiation
      potential qualifies them as adult stem cells. However, it is currently unclear
      whether neural lineages arise from dedifferentiated Schwann cells instead of
      mesodermally derived dermal precursor cells. To clarify these discrepancies, we
      traced SOX2+ adult dermal precursor cells by two independent Myf5 lineage tracing
      strains. We demonstrate that dermal Schwann cells do not belong to the Myf5+ cell
      lineage, indicating that previous tracing data reflected aberrant cre recombinase
      expression and that bona fide Myf5+ dermal precursors cannot transdifferentiate
      to neural lineages in physiological conditions.

PMID- 29033304
TI  - Epigenetic Activation of Pro-angiogenic Signaling Pathways in Human Endothelial
      Progenitors Increases Vasculogenesis.
AB  - Human endothelial colony-forming cells (ECFCs) represent a promising source of
      adult stem cells for vascular repair, yet their regenerative capacity is limited.
      Here, we set out to understand the molecular mechanism restricting the repair
      function of ECFCs. We found that key pro-angiogenic pathways are repressed in
      ECFCs due to the presence of bivalent (H3K27me3/H3K4me3) epigenetic marks, which
      decreases the cells' regenerative potential. Importantly, ex vivo treatment with
      a combination of epigenetic drugs that resolves bivalent marks toward the
      transcriptionally active H3K4me3 state leads to the simultaneous activation of
      multiple pro-angiogenic signaling pathways (VEGFR, CXCR4, WNT, NOTCH, SHH). This
      in turn results in improved capacity of ECFCs to form capillary-like networks in
      vitro and in vivo. Furthermore, restoration of perfusion is accelerated upon
      transplantation of drug-treated ECFCs in a model of hindlimb ischemia. Thus, ex
      vivo treatment with epigenetic drugs increases the vascular repair properties of
      ECFCs through transient activation of pro-angiogenic signaling pathways.

PMID- 29033305
TI  - Machine Learning of Human Pluripotent Stem Cell-Derived Engineered Cardiac Tissue
      Contractility for Automated Drug Classification.
AB  - Accurately predicting cardioactive effects of new molecular entities for
      therapeutics remains a daunting challenge. Immense research effort has been
      focused toward creating new screening platforms that utilize human pluripotent
      stem cell (hPSC)-derived cardiomyocytes and three-dimensional engineered cardiac
      tissue constructs to better recapitulate human heart function and drug responses.
      As these new platforms become increasingly sophisticated and high throughput, the
      drug screens result in larger multidimensional datasets. Improved automated
      analysis methods must therefore be developed in parallel to fully comprehend the
      cellular response across a multidimensional parameter space. Here, we describe
      the use of machine learning to comprehensively analyze 17 functional parameters
      derived from force readouts of hPSC-derived ventricular cardiac tissue strips
      (hvCTS) electrically paced at a range of frequencies and exposed to a library of
      compounds. A generated metric is effective for then determining the
      cardioactivity of a given drug. Furthermore, we demonstrate a classification
      model that can automatically predict the mechanistic action of an unknown
      cardioactive drug.

PMID- 29033306
TI  - Oocyte-Specific Homeobox 1, Obox1, Facilitates Reprogramming by Promoting
      Mesenchymal-to-Epithelial Transition and Mitigating Cell Hyperproliferation.
AB  - Mammalian oocytes possess fascinating unknown factors, which can reprogram
      terminally differentiated germ cells or somatic cells into totipotent embryos.
      Here, we demonstrate that oocyte-specific homeobox 1 (Obox1), an oocyte-specific
      factor, can markedly enhance the generation of induced pluripotent stem cells
      (iPSCs) from mouse fibroblasts in a proliferation-independent manner and can
      replace Sox2 to achieve pluripotency. Overexpression of Obox1 can greatly promote
      mesenchymal-to-epithelial transition (MET) at early stage of OSKM-induced
      reprogramming, and meanwhile, the hyperproliferation of THY1-positive cells can
      be significantly mitigated. Subsequently, the proportion of THY1-negative cells
      and Oct4-GFP-positive cells increased dramatically. Further analysis of gene
      expression and targets of Obox1 during reprogramming indicates that the
      expression of Obox1 can promote epithelial gene expression and modulate cell
      cycle-related gene expression. Taken together, we conclude that the oocyte
      specific factor Obox1 serves as a strong activator for somatic cell reprogramming
      through promoting the MET and mitigating cell hyperproliferation.

PMID- 29033308
TI  - 2017 Annual Meeting of the American College of Radiology-Moreton Lecture:
      Forecasting the Futures of Radiology.
AB  - PURPOSE: The traditional forces of change in health care are no longer working as
      they did in the past. Political gridlock has destroyed Washington's ability to
      create sensible policy for reforming the medical marketplace, creating chaos for
      providers. Fortunately, chaos creates opportunity. The idea of creating one's
      future has never been more relevant and necessary. MATERIALS AND METHODS:
      Predicting-the science of extrapolating future values from historical data-is not
      a valid method for looking ahead when causal relationships that explained change
      in the past are themselves being redefined (the current situation). Forecasting
      the art of estimating probabilities of possibilities-is the appropriate method
      for anticipating futures when causality is being redefined. With its focus on
      identifying a range of possibilities, forecasting identifies many different
      outcomes that are simultaneously possible for radiology. RESULTS: Health care's
      new climate is being shaped by four defining trends: 1) revolution in biological
      science that is shifting caregivers' mission from acute care to disease
      management; 2) proliferation of information and communications technologies that
      are transforming the way care is delivered; 3) end of economic growth in the
      medical marketplace that is reshaping demand for care; and 4) political
      dysfunction that forces caregivers and their business partners to develop
      successful futures on their own. CONCLUSIONS: Radiology 3.0 is nicely aligned
      with the transformational trends. Staying focused on implementing Radiology 3.0
      is supported as the optimal strategy for creating the profession's futures.
      Diagnostic convergence, establishing a unified diagnostic science with laboratory
      medicine, is proposed as a complementary initiative.

PMID- 29033309
TI  - Ethical considerations in prenatal testing: Genomic testing and medical
      uncertainty.
AB  - Prenatal diagnostic testing has recently progressed from karyotype to routinely
      available chromosomal microarray, and the potential for fetal whole exome
      sequencing, both through invasive diagnostic testing and, in some cases, non
      invasive prenatal testing. These tests bring beneficence through providing a
      higher diagnostic yield, often with lower risks of miscarriage than previously
      available testing, but also raise the question of harms related to an increase in
      uncertain and unknown results. Some parents-to-be report a desire to learn as
      much information as possible prenatally, and there may be beneficence in
      providing them with this information. However, the potential uncertainty these
      tests may create may raise anxiety and may complicate pregnancy decision-making
      for both patients and providers. This article reviews current prenatal
      technologies and the growing research on the clinical and ethical aspects of
      uncertainty as it relates to expanding prenatal testing options.

PMID- 29033307
TI  - NEUROG1 Regulates CDK2 to Promote Proliferation in Otic Progenitors.
AB  - Loss of spiral ganglion neurons (SGNs) significantly contributes to hearing loss.
      Otic progenitor cell transplantation is a potential strategy to replace lost
      SGNs. Understanding how key transcription factors promote SGN differentiation in
      otic progenitors accelerates efforts for replacement therapies. A pro-neural
      transcription factor, Neurogenin1 (Neurog1), is essential for SGN development.
      Using an immortalized multipotent otic progenitor (iMOP) cell line that can self
      renew and differentiate into otic neurons, NEUROG1 was enriched at the promoter
      of cyclin-dependent kinase 2 (Cdk2) and neurogenic differentiation 1 (NeuroD1)
      genes. Changes in H3K9ac and H3K9me3 deposition at the Cdk2 and NeuroD1 promoters
      suggested epigenetic regulation during iMOP proliferation and differentiation. In
      self-renewing iMOP cells, overexpression of NEUROG1 increased CDK2 to drive
      proliferation, while knockdown of NEUROG1 decreased CDK2 and reduced
      proliferation. In iMOP-derived neurons, overexpression of NEUROG1 accelerated
      acquisition of neuronal morphology, while knockdown of NEUROG1 prevented
      differentiation. Our findings suggest that NEUROG1 can promote proliferation or
      neuronal differentiation.

PMID- 29033310
TI  - Relation of elevated serum uric acid levels to first-degree heart block and other
      cardiac conduction defects in hospitalized patients with type 2 diabetes.
AB  - AIMS: Several studies have reported that moderately elevated serum uric acid
      levels are associated with an increased risk of tachyarrhythmias (mainly atrial
      fibrillation) in patients with and without type 2 diabetes mellitus (T2DM). It is
      currently unknown whether an association also exists between elevated serum uric
      acid levels and cardiac conduction defects in patients with T2DM. METHODS: We
      retrospectively analyzed a hospital-based sample of 967 patients with T2DM
      discharged from our Division of Endocrinology over the years 2007-2014. Standard
      electrocardiograms were performed on all patients and were interpreted by expert
      cardiologists. RESULTS: Overall, 267 (27.6%) patients had some type of conduction
      defects on electrocardiograms (defined as at least one block among first-degree
      atrio-ventricular block, second-degree block, third-degree block, left bundle
      branch block, right bundle branch block, left anterior hemi-block or left
      posterior hemi-block). Patients in the 3rd serum uric acid tertile had a higher
      prevalence of any cardiac conduction defects than those belonging to 2nd or 1st
      tertile, respectively (35.8% vs. 25.0% vs. 22.6%; p<0.0001). Elevated serum uric
      acid levels were associated with a nearly twofold increased risk of cardiac
      conduction defects after adjustment for age, sex, hemoglobin A1c, diabetes
      duration, metabolic syndrome, chronic kidney disease, chronic obstructive
      pulmonary disease, ischemic heart disease, valvular heart disease and medication
      use (adjusted-odds ratio 1.84, 95% confidence intervals 1.2-2.9; p=0.009).
      CONCLUSIONS: Moderately elevated serum uric acid levels are associated with an
      increased prevalence of any cardiac conduction defects in hospitalized patients
      with T2DM, independent of multiple risk factors and potential confounding
      variables.

PMID- 29033311
TI  - Brain gray matter changes in type 2 diabetes mellitus: A meta-analysis of whole
      brain voxel-based morphometry study.
AB  - AIMS: We aimed to identify alterations in global gray matter volumes (GMV) and
      consistent regional abnormalities in T2DM patients via meta-analysis. METHODS: A
      systematic search for relevant studies indexed in the PubMed and Embase databases
      was conducted. A quantitative meta-analysis of volumetric and whole-brain VBM
      data was conducted using STATA v.12.0 and AES-SDM software packages,
      respectively. RESULTS: A total of 15 volumetric studies and five VBM studies of
      GM in T2DM patients vs. healthy controls (HCs) were identified. The volumetric
      meta-analysis showed that the GMV of patients with T2DM is lower than in HCs (SMD
      = -0.56, 95% CI = -0.81 to -0.31, P 0.01). The whole-brain VBM meta-analysis
      revealed GM reductions in the left superior temporal gyrus, the right middle
      temporal gyrus, the right rolandic operculum, and the left fusiform gyrus in T2DM
      patients compared with HCs. Meta-regression analysis showed that Mini-Mental
      State Examination (MMSE) scores have a positive relationship with GMV in the
      right insula. CONCLUSIONS: The results showed a reduced volume of whole and
      regional GM in T2DM patients, which may indicate a risk for dementia. Further
      longitudinal research is needed to confirm GM changes, cognitive dysfunction, and
      their relationship in T2DM.

PMID- 29033312
TI  - Higher serum albumin was related with diabetes incidence and the impact of BMI
      changes: Based on cohort study of 18,384 Chinese male elderly.
AB  - AIMS: Albumin (ALB) was a useful marker of nutrition and general health status.
      However, the conclusion about the association between ALB and diabetes was
      inconsistent, and little information was known about the elderly. METHODS: A
      cohort study based on 18,384 army cadres was conducted Beijing, from 2009 to
      2013. RESULTS: The mean age of the total 18,384 participants was 71+/-14years,
      and the mean ALB concentration was 44.33+/-3.94g/L at baseline. Diabetes incident
      showed an increasing trend according to the four ALB concentration groups, from
      2.054% to 2.811% for incident. Cox regression showed that participants with
      higher ALB concentration were at increased HRs for diabetes incident. The HRs of
      ALB (per SD) and ALB concentration for diabetes were 1.125 (95% CI: 1.024-1.231)
      and 1.029 (95% CI: 1.007-1.051) respectively in the adjusted model. Also the HRs
      were closely related with BMI changes. For those who had a BMI changes<
      1.00kg/m2, the HRs were lower and not statistically significant, and for those
      with increasing BMI during an average of 4years' follow-up, the HRs were higher.
      CONCLUSION: There was a positive and independent association between baseline ALB
      concentrations with diabetes incident among Chinese male elderly, and this
      association was closely related with BMI changes.

PMID- 29033313
TI  - Developing a model for cystic fibrosis sociomicrobiology based on antibiotic and
      environmental stress.
AB  - Cystic fibrosis (CF) infections are invariably biofilm-mediated and
      polymicrobial, being safe to assume that a myriad of factors affects the
      sociomicrobiology within the CF infection site and modulate the CF community
      dynamics, by shaping their social activities, overall functions, virulence,
      ultimately affecting disease outcome. This work aimed to assess changes in the
      dynamics (particularly on the microbial composition) of dual-/three-species
      biofilms involving CF-classical (Pseudomonas aeruginosa) and unusual species
      (Inquilinus limosus and Dolosigranulum pigrum), according to variable oxygen
      conditions and antibiotic exposure. Low fluctuations in biofilm compositions were
      observed across distinct oxygen environments, with dual-species biofilms
      exhibiting similar relative proportions and P. aeruginosa and/or D. pigrum
      populations dominating three-species consortia. Once exposed to antibiotics,
      biofilms displayed high resistance profiles, and microbial compositions,
      distributions, and microbial interactions significantly challenged. The
      antibiotic/oxygen environment supported such fluctuations, which enhanced for
      three-species communities. In conclusion, antibiotic therapy hugely disturbed CF
      communities' dynamics, inducing significant compositional changes on multispecies
      consortia. Clearly, multiple perturbations may disturb this dynamic, giving rise
      to various microbiological scenarios in vivo, and affecting disease phenotype.
      Therefore, an appreciation of the ecological/evolutionary nature within CF
      communities will be useful for the optimal use of current therapies and for newer
      breakthroughs on CF antibiotherapy.

PMID- 29033315
TI  - Very Long Chain Fatty Acids Are Functionally Involved in Necroptosis.
AB  - Necroptosis is a form of regulated cell death that is linked to various human
      diseases. Distinct membrane-related, thus lipid-dependent, alterations take place
      during necroptosis. However, little is known about the roles of specific lipids
      in this process. We used an untargeted LC-MS-based approach to reveal that
      distinct lipid species are regulated at the molecular level during necroptosis.
      We found that ceramides and very long chain fatty acids accumulate during this
      process. Intrigued by the specificity of very long chain fatty acid accumulation,
      we focused on characterizing their involvement during necroptosis. Biochemical
      characterizations suggested that activated fatty acid biosynthesis and elongation
      could be responsible for these accumulations. We further showed that inhibition
      of fatty acid biosynthesis and depletion of very long chain fatty acids prevented
      loss of plasma membrane integrity and cell death, strongly suggesting that very
      long chain fatty acids are functionally involved in necroptosis.

PMID- 29033314
TI  - Analysis of threshold stenosis by multiplanar venogram and intravascular
      ultrasound examination for predicting clinical improvement after iliofemoral vein
      stenting in the VIDIO trial.
AB  - BACKGROUND: Selecting patients for iliofemoral vein stenting has traditionally
      relied on the identification and quantification of stenotic lesions with imaging
      such as multiplanar venography. Recently, intravascular ultrasound (IVUS) imaging
      has become more available. However, to date, the usefulness of these imaging
      modalities using the customary >50% treatment threshold for diameter (multiplanar
      venography) and area (IVUS) stenosis of iliofemoral veins has not been validated
      prospectively within the context of clinical improvement. METHODS: The
      multicenter Venogram Versus Intravascular Ultrasound for Diagnosing and Treating
      Iliofemoral Vein Obstruction (VIDIO) trial prospectively enrolled 100 symptomatic
      patients (Clinical Etiologic Anatomic Pathophysiologic [CEAP] classification of 4
      6) with suspected iliofemoral venous outflow disease. Venous stenting for
      presumed significant iliofemoral vein stenosis, based on imaging and clinical
      findings, was performed on 68 patients. Based on imaging, stenosis was
      characterized as nonthrombotic in 48 patients and post-thrombotic in 20 patients.
      Each underwent baseline and poststenting venography and IVUS to compare the
      diagnostic and clinical usefulness of the tests. The revised Venous Clinical
      Severity Score was used to assess clinical patient outcome. A >4-point reduction
      in the revised Venous Clinical Severity Score between baseline and 6 months was
      used as an indicator of clinically meaningful improvement. Receiver operating
      characteristic curve analysis was used to determine the optimal diameter and area
      thresholds for prediction of clinical improvement. RESULTS: Clinical improvement
      after stenting was best predicted by IVUS baseline measurement of area stenosis
      (area under the curve, 0.64; P = .04), with >54% estimated as the optimal
      threshold of stenosis indicating interventional treatment. With measurement of
      lumen gain from baseline to after the procedure, the optimal reduction in vein
      stenosis correlative of later clinical improvement was >41%; IVUS measurement of
      area stenosis was most predictive (area under the curve, 0.70; P = .004).
      Venographic measurements of baseline stenosis and stenotic change were not
      predictive of later improvement. In a 48-patient nonthrombotic subset analysis,
      IVUS diameter rather than area measurements of baseline stenosis were
      significantly predictive of clinical success, but indicated a higher optimal
      threshold of stenosis (>61%) may be necessary. CONCLUSIONS: This study suggests
      that IVUS shows significant usefulness at predicting when stenting iliofemoral
      vein stenosis in patients clinical-etiologic-anatomic-pathophysiologic
      classification of 4-6 will result in significant symptom improvement. Our
      findings corroborate the conventional >50% cross-sectional area threshold by IVUS
      as defining a clinically significant iliofemoral stenosis that, when stented, has
      significant predictive value for symptom improvement. In nonthrombotic patients,
      however, a threshold of >61% diameter stenosis by IVUS may better predict
      clinical improvement.

PMID- 29033316
TI  - Synergy and Target Promiscuity Drive Structural Divergence in Bacterial
      Alkylquinolone Biosynthesis.
AB  - Microbial natural products are genetically encoded by dedicated biosynthetic gene
      clusters (BGCs). A given BGC usually produces a family of related compounds that
      share a core but contain variable substituents. Though common, the reasons
      underlying this divergent biosynthesis are in general unknown. Herein, we have
      addressed this issue using the hydroxyalkylquinoline (HAQ) family of natural
      products synthesized by Burkholderia thailandensis. Investigations into the
      detailed functions of two analogs show that they act synergistically in
      inhibiting bacterial growth. One analog is a nanomolar inhibitor of pyrimidine
      biosynthesis and at the same time disrupts the proton motive force. A second
      analog inhibits the cytochrome bc1 complex as well as pyrimidine biogenesis.
      These results provide a functional rationale for the divergent nature of HAQs.
      They imply that synergy and target promiscuity are driving forces for the
      evolution of tailoring enzymes that diversify the products of the HAQ
      biosynthetic pathway.

PMID- 29033318
TI  - An Alkynyl-Fucose Halts Hepatoma Cell Migration and Invasion by Inhibiting GDP
      Fucose-Synthesizing Enzyme FX, TSTA3.
AB  - Fucosylation is a glycan modification critically involved in cancer and
      inflammation. Although potent fucosylation inhibitors are useful for basic and
      clinical research, only a few inhibitors have been developed. Here, we focus on a
      fucose analog with an alkyne group, 6-alkynyl-fucose (6-Alk-Fuc), which is used
      widely as a detection probe for fucosylated glycans, but is also suggested for
      use as a fucosylation inhibitor. Our glycan analysis using lectin and mass
      spectrometry demonstrated that 6-Alk-Fuc is a potent and general inhibitor of
      cellular fucosylation, with much higher potency than the existing inhibitor, 2
      fluoro-fucose (2-F-Fuc). The action mechanism was shown to deplete cellular GDP
      Fuc, and the direct target of 6-Alk-Fuc is FX (encoded by TSTA3), the
      bifunctional GDP-Fuc synthase. We also show that 6-Alk-Fuc halts hepatoma
      invasion. These results highlight the unappreciated role of 6-Alk-Fuc as a
      fucosylation inhibitor and its potential use for basic and clinical science.

PMID- 29033317
TI  - Ras Binder Induces a Modified Switch-II Pocket in GTP and GDP States.
AB  - Covalent inhibitors of K-Ras(G12C) have been reported that exclusively recognize
      the GDP state. Here, we utilize disulfide tethering of a non-natural cysteine (K
      Ras(M72C)) to identify a new switch-II pocket (S-IIP) binding ligand (2C07) that
      engages the active GTP state. Co-crystal structures of 2C07 bound to H-Ras(M72C)
      reveal binding in a cryptic groove we term S-IIG. In the GppNHp state, 2C07
      binding to a modified S-IIP pushes switch I away from the nucleotide, breaking
      the network of polar contacts essential for adopting the canonical GTP state.
      Biochemical studies show that 2C07 alters nucleotide preference and inhibits SOS
      binding and catalyzed nucleotide exchange. 2C07 was converted to irreversible
      covalent analogs, which target both nucleotide states, inhibit PI3K activation in
      vitro, and function as occupancy probes to detect reversible engagement in
      competition assays. Targeting both nucleotide states opens the possibility of
      inhibiting oncogenic mutants of Ras, which exist predominantly in the GTP state
      in cells.

PMID- 29033321
TI  - Regulation of m6A Transcripts by the 3'->5' RNA Helicase YTHDC2 Is Essential for
      a Successful Meiotic Program in the Mammalian Germline.
AB  - N6-methyladenosine (m6A) is an essential internal RNA modification that is
      critical for gene expression control in most organisms. Proteins with a YTH
      domain recognize m6A marks and are mediators of molecular functions like RNA
      splicing, mRNA decay, and translation control. Here we demonstrate that YTH
      domain-containing 2 (YTHDC2) is an m6A reader that is essential for male and
      female fertility in mice. High-throughput mapping of the m6A transcriptome and
      expression analysis in the Yhtdc2 mutant testes reveal an upregulation of m6A
      enriched transcripts. Our biochemical studies indicate that YTHDC2 is an RNA
      induced ATPase with a 3'->5' RNA helicase activity. Furthermore, YTHDC2 recruits
      the 5'->3' exoribonuclease XRN1 via Ankyrin repeats that are inserted in between
      the RecA modules of the RNA helicase domain. Our studies reveal a role for YTHDC2
      in modulating the levels of m6A-modified germline transcripts to maintain a gene
      expression program that is conducive for progression through meiosis.

PMID- 29033320
TI  - Mitophagy Controls the Activities of Tumor Suppressor p53 to Regulate Hepatic
      Cancer Stem Cells.
AB  - Autophagy is required for benign hepatic tumors to progress into malignant
      hepatocellular carcinoma. However, the mechanism is unclear. Here, we report that
      mitophagy, the selective removal of mitochondria by autophagy, positively
      regulates hepatic cancer stem cells (CSCs) by suppressing the tumor suppressor
      p53. When mitophagy is enhanced, p53 co-localizes with mitochondria and is
      removed by a mitophagy-dependent manner. However, when mitophagy is inhibited,
      p53 is phosphorylated at serine-392 by PINK1, a kinase associated with mitophagy,
      on mitochondria and translocated into the nucleus, where it binds to the NANOG
      promoter to prevent OCT4 and SOX2 transcription factors from activating the
      expression of NANOG, a transcription factor critical for maintaining the stemness
      and the self-renewal ability of CSCs, resulting in the reduction of hepatic CSC
      populations. These results demonstrate that mitophagy controls the activities of
      p53 to maintain hepatic CSCs and provide an explanation as to why autophagy is
      required to promote hepatocarcinogenesis.

PMID- 29033319
TI  - Checkpoint Kinase Rad53 Couples Leading- and Lagging-Strand DNA Synthesis under
      Replication Stress.
AB  - The checkpoint kinase Rad53 is activated during replication stress to prevent
      fork collapse, an essential but poorly understood process. Here we show that
      Rad53 couples leading- and lagging-strand synthesis under replication stress. In
      rad53-1 cells stressed by dNTP depletion, the replicative DNA helicase, MCM, and
      the leading-strand DNA polymerase, Pol epsilon, move beyond the site of DNA
      synthesis, likely unwinding template DNA. Remarkably, DNA synthesis progresses
      further along the lagging strand than the leading strand, resulting in the
      exposure of long stretches of single-stranded leading-strand template. The
      asymmetric DNA synthesis in rad53-1 cells is suppressed by elevated levels of
      dNTPs in vivo, and the activity of Pol epsilon is compromised more than lagging
      strand polymerase Pol delta at low dNTP concentrations in vitro. Therefore, we
      propose that Rad53 prevents the generation of excessive ssDNA under replication
      stress by coordinating DNA unwinding with synthesis of both strands.

PMID- 29033322
TI  - Structural Basis of Mec1-Ddc2-RPA Assembly and Activation on Single-Stranded DNA
      at Sites of Damage.
AB  - Mec1-Ddc2 (ATR-ATRIP) is a key DNA-damage-sensing kinase that is recruited
      through the single-stranded (ss) DNA-binding replication protein A (RPA) to
      initiate the DNA damage checkpoint response. Activation of ATR-ATRIP in the
      absence of DNA damage is lethal. Therefore, it is important that damage-specific
      recruitment precedes kinase activation, which is achieved at least in part by
      Mec1-Ddc2 homodimerization. Here, we report a structural, biochemical, and
      functional characterization of the yeast Mec1-Ddc2-RPA assembly. High-resolution
      co-crystal structures of Ddc2-Rfa1 and Ddc2-Rfa1-t11 (K45E mutant) N termini and
      of the Ddc2 coiled-coil domain (CCD) provide insight into Mec1-Ddc2
      homodimerization and damage-site targeting. Based on our structural and
      functional findings, we present a Mec1-Ddc2-RPA-ssDNA composite structural model.
      By way of validation, we show that RPA-dependent recruitment of Mec1-Ddc2 is
      crucial for maintaining its homodimeric state at ssDNA and that Ddc2's
      recruitment domain and CCD are important for Mec1-dependent survival of UV-light
      induced DNA damage.

PMID- 29033323
TI  - mTORC1 Phosphorylates Acetyltransferase p300 to Regulate Autophagy and
      Lipogenesis.
AB  - Acetylation is increasingly recognized as one of the major post-translational
      mechanisms for the regulation of multiple cellular functions in mammalian cells.
      Acetyltransferase p300, which acetylates histone and non-histone proteins, has
      been intensively studied in its role in cell growth and metabolism. However, the
      mechanism underlying the activation of p300 in cells remains largely unknown.
      Here, we identify the homeostatic sensor mTORC1 as a direct activator of p300.
      Activated mTORC1 interacts with p300 and phosphorylates p300 at 4 serine residues
      in the C-terminal domain. Mechanistically, phosphorylation of p300 by mTORC1
      prevents the catalytic HAT domain from binding to the RING domain, thereby
      eliminating intra-molecular inhibition. Functionally, mTORC1-dependent
      phosphorylation of p300 suppresses cell-starvation-induced autophagy and
      activates cell lipogenesis. These results uncover p300 as a direct target of
      mTORC1 and suggest that the mTORC1-p300 pathway plays a pivotal role in cell
      metabolism by coordinately controlling cell anabolism and catabolism.

PMID- 29033326
TI  - Genetic Discontinuity between the Maritime Archaic and Beothuk Populations in
      Newfoundland, Canada.
AB  - Situated at the furthest northeastern edge of Canada, the island of Newfoundland
      (approximately 110,000 km2) and Labrador (approximately 295,000 km2) today
      constitute a province characterized by abundant natural resources but low
      population density. Both landmasses were covered by the Laurentide ice sheet
      during the Last Glacial Maximum (18,000 years before present [YBP]); after the
      glacier retreated, ice patches remained on the island until ca. 9,000 calibrated
      (cal) YBP [1]. Nevertheless, indigenous peoples, whose ancestors had trekked some
      5,000 km from the west coast, arrived approximately 10,000 cal YBP in Labrador
      and ca. 6,000 cal YBP in Newfoundland [2, 3]. Differential features in material
      culture indicate at least three settlement episodes by distinct cultural groups,
      including the Maritime Archaic, Palaeoeskimo, and Beothuk. Newfoundland has
      remained home to indigenous peoples until present day with only one apparent
      hiatus (3,400-2,800 YBP). This record suggests abandonment, severe constriction,
      or local extinction followed by subsequent immigrations from single or multiple
      source populations, but the specific dynamics and the cultural and biological
      relationships, if any, among these successive peoples remain enigmatic [4]. By
      examining the mitochondrial genome diversity and isotopic ratios of 74 ancient
      remains in conjunction with the archaeological record, we have provided
      definitive evidence for the genetic discontinuity between the maternal lineages
      of these populations. This northeastern margin of North America appears to have
      been populated multiple times by distinct groups that did not share a recent
      common ancestry, but rather one much deeper in time at the entry point into the
      continent.

PMID- 29033325
TI  - Effect of Lower-Limb Progressive Resistance Exercise After Hip Fracture Surgery:
      A Systematic Review and Meta-Analysis of Randomized Controlled Studies.
AB  - OBJECTIVE: Although several studies have reported the effect of progressive
      resistance exercise (PRE) after hip fracture surgery, little is known about the
      functional efficacy of PRE. Thus, we conducted a meta-analysis to evaluate
      whether PRE can improve (1) mobility and (2) other physical functions in elderly
      patients after hip fracture surgery. METHODS: Eight randomized controlled trials
      investigating the effects of PRE after hip fracture surgery were retrieved from a
      PubMed, Embase, and Cochrane Library search. Our pair-wise meta-analysis used a
      fixed or random effects model. RESULTS: PRE significantly improved participants'
      overall physical functions after hip fracture surgery compared with the control
      group (standardized mean difference = 0.408; 95% confidence interval, 0.238
      0.578; P < .001). It was particularly effective in the areas of mobility
      (standardized mean difference = 0.501; 95% confidence interval, 0.297-0.705; P <
      .001), activities of daily living, balance, lower-limb strength or power, and
      performance task. CONCLUSIONS: Our meta-analysis revealed that PRE after hip
      fracture surgery improves mobility, activities of daily living, balance, lower
      limb strength or power, and performance task outcomes. Because of the small
      sample size in this meta-analysis and considering the increasing incidence of hip
      fractures, there is a need for large-scale randomized controlled trials to
      confirm the functional improvement and adverse effects of PRE.

PMID- 29033324
TI  - The Elongation Factor Spt6 Maintains ESC Pluripotency by Controlling Super
      Enhancers and Counteracting Polycomb Proteins.
AB  - Spt6 coordinates nucleosome dis- and re-assembly, transcriptional elongation, and
      mRNA processing. Here, we report that depleting Spt6 in embryonic stem cells
      (ESCs) reduced expression of pluripotency factors, increased expression of cell
      lineage-affiliated developmental regulators, and induced cell morphological and
      biochemical changes indicative of ESC differentiation. Selective downregulation
      of pluripotency factors upon Spt6 depletion may be mechanistically explained by
      its enrichment at ESC super-enhancers, where Spt6 controls histone H3K27
      acetylation and methylation and super-enhancer RNA transcription. In ESCs, Spt6
      interacted with the PRC2 core subunit Suz12 and prevented H3K27me3 accumulation
      at ESC super-enhancers and associated promoters. Biochemical as well as
      functional experiments revealed that Spt6 could compete for binding of the PRC2
      methyltransferase Ezh2 to Suz12 and reduce PRC2 chromatin engagement. Thus, in
      addition to serving as a histone chaperone and transcription elongation factor,
      Spt6 counteracts repression by opposing H3K27me3 deposition at critical genomic
      regulatory regions.

PMID- 29033327
TI  - 40,000-Year-Old Individual from Asia Provides Insight into Early Population
      Structure in Eurasia.
AB  - By at least 45,000 years before present, anatomically modern humans had spread
      across Eurasia [1-3], but it is not well known how diverse these early
      populations were and whether they contributed substantially to later people or
      represent early modern human expansions into Eurasia that left no surviving
      descendants today. Analyses of genome-wide data from several ancient individuals
      from Western Eurasia and Siberia have shown that some of these individuals have
      relationships to present-day Europeans [4, 5] while others did not contribute to
      present-day Eurasian populations [3, 6]. As contributions from Upper Paleolithic
      populations in Eastern Eurasia to present-day humans and their relationship to
      other early Eurasians is not clear, we generated genome-wide data from a 40,000
      year-old individual from Tianyuan Cave, China, [1, 7] to study his relationship
      to ancient and present-day humans. We find that he is more related to present-day
      and ancient Asians than he is to Europeans, but he shares more alleles with a
      35,000-year-old European individual than he shares with other ancient Europeans,
      indicating that the separation between early Europeans and early Asians was not a
      single population split. We also find that the Tianyuan individual shares more
      alleles with some Native American groups in South America than with Native
      Americans elsewhere, providing further support for population substructure in
      Asia [8] and suggesting that this persisted from 40,000 years ago until the
      colonization of the Americas. Our study of the Tianyuan individual highlights the
      complex migration and subdivision of early human populations in Eurasia.

PMID- 29033329
TI  - Nanoscale Visualization of Biomineral Formation in Coral Proto-Polyps.
AB  - Calcium carbonate platforms produced by reef-building stony corals over geologic
      time are pervasive features around the world [1]; however, the mechanism by which
      these organisms produce the mineral is poorly understood (see review by [2]). It
      is generally assumed that stony corals precipitate calcium carbonate
      extracellularly as aragonite in a calcifying medium between the calicoblastic
      ectoderm and pre-existing skeleton, separated from the overlying seawater [2].
      The calicoblastic ectoderm produces extracellular matrix (ECM) proteins, secreted
      to the calcifying medium [3-6], which appear to provide the nucleation,
      alteration, elongation, and inhibition mechanisms of the biomineral [7] and
      remain occluded and preserved in the skeleton [8-10]. Here we show in cell
      cultures of the stony coral Stylophora pistillata that calcium is concentrated in
      intracellular pockets that are subsequently exported from the cell where a
      nucleation process leads to the formation of extracellular aragonite crystals.
      Analysis of the growing crystals by lattice light-sheet microscopy suggests that
      the crystals elongate from the cells' surfaces outward.

PMID- 29033328
TI  - The Cys-Arg/N-End Rule Pathway Is a General Sensor of Abiotic Stress in Flowering
      Plants.
AB  - Abiotic stresses impact negatively on plant growth, profoundly affecting yield
      and quality of crops. Although much is known about plant responses, very little
      is understood at the molecular level about the initial sensing of environmental
      stress. In plants, hypoxia (low oxygen, which occurs during flooding) is directly
      sensed by the Cys-Arg/N-end rule pathway of ubiquitin-mediated proteolysis,
      through oxygen-dependent degradation of group VII Ethylene Response Factor
      transcription factors (ERFVIIs) via amino-terminal (Nt-) cysteine [1, 2]. Using
      Arabidopsis (Arabidopsis thaliana) and barley (Hordeum vulgare), we show that the
      pathway regulates plant responses to multiple abiotic stresses. In Arabidopsis,
      genetic analyses revealed that response to these stresses is controlled by N-end
      rule regulation of ERFVII function. Oxygen sensing via the Cys-Arg/N-end rule in
      higher eukaryotes is linked through a single mechanism to nitric oxide (NO)
      sensing [3, 4]. In plants, the major mechanism of NO synthesis is via NITRATE
      REDUCTASE (NR), an enzyme of nitrogen assimilation [5]. Here, we identify a
      negative relationship between NR activity and NO levels and stabilization of an
      artificial Nt-Cys substrate and ERFVII function in response to environmental
      changes. Furthermore, we show that ERFVIIs enhance abiotic stress responses via
      physical and genetic interactions with the chromatin-remodeling ATPase BRAHMA. We
      propose that plants sense multiple abiotic stresses through the Cys-Arg/N-end
      rule pathway either directly (via oxygen sensing) or indirectly (via NO sensing
      downstream of NR activity). This single mechanism can therefore integrate
      environment and response to enhance plant survival.

PMID- 29033330
TI  - Exocrine Gland-Secreting Peptide 1 Is a Key Chemosensory Signal Responsible for
      the Bruce Effect in Mice.
AB  - The Bruce effect refers to pregnancy termination in recently pregnant female
      rodents upon exposure to unfamiliar males [1]. This event occurs in specific
      combinations of laboratory mouse strains via the vomeronasal system [2, 3];
      however, the responsible chemosensory signals have not been fully identified.
      Here we demonstrate that the male pheromone exocrine gland-secreting peptide 1
      (ESP1) is one of the key factors that causes pregnancy block. Female mice
      exhibited high pregnancy failure rates upon encountering males that secreted
      different levels of ESP1 compared to the mated male. The effect was not observed
      in mice that lacked the ESP1 receptor, V2Rp5, which is expressed in vomeronasal
      sensory neurons. Prolactin surges in the blood after mating, which are essential
      for maintaining luteal function, were suppressed by ESP1 exposure, suggesting
      that a neuroendocrine mechanism underlies ESP1-mediated pregnancy failure. The
      single peptide pheromone ESP1 conveys not only maleness to promote female
      receptivity but also the males' characteristics to facilitate memorization of the
      mating partner.

PMID- 29033331
TI  - Transcranial Direct Current Stimulation Facilitates Associative Learning and
      Alters Functional Connectivity in the Primate Brain.
AB  - There has been growing interest in transcranial direct current stimulation
      (tDCS), a non-invasive technique purported to modulate neural activity via weak,
      externally applied electric fields. Although some promising preliminary data have
      been reported for applications ranging from stroke rehabilitation to cognitive
      enhancement, little is known about how tDCS affects the human brain, and some
      studies have concluded that it may have no effect at all. Here, we describe a
      macaque model of tDCS that allows us to simultaneously examine the effects of
      tDCS on brain activity and behavior. We find that applying tDCS to right
      prefrontal cortex improves monkeys' performance on an associative learning task.
      While firing rates do not change within the targeted area, tDCS does induce large
      low-frequency oscillations in the underlying tissue. These oscillations alter
      functional connectivity, both locally and between distant brain areas, and these
      long-range changes correlate with tDCS's effects on behavior. Together, these
      results are consistent with the idea that tDCS leads to widespread changes in
      brain activity and suggest that it may be a valuable method for cheaply and non
      invasively altering functional connectivity in humans.

PMID- 29033333
TI  - Mothers Consistently Alter Their Unique Vocal Fingerprints When Communicating
      with Infants.
AB  - The voice is the most direct link we have to others' minds, allowing us to
      communicate using a rich variety of speech cues [1, 2]. This link is particularly
      critical early in life as parents draw infants into the structure of their
      environment using infant-directed speech (IDS), a communicative code with unique
      pitch and rhythmic characteristics relative to adult-directed speech (ADS) [3,
      4]. To begin breaking into language, infants must discern subtle statistical
      differences about people and voices in order to direct their attention toward the
      most relevant signals. Here, we uncover a new defining feature of IDS: mothers
      significantly alter statistical properties of vocal timbre when speaking to their
      infants. Timbre, the tone color or unique quality of a sound, is a spectral
      fingerprint that helps us instantly identify and classify sound sources, such as
      individual people and musical instruments [5-7]. We recorded 24 mothers'
      naturalistic speech while they interacted with their infants and with adult
      experimenters in their native language. Half of the participants were English
      speakers, and half were not. Using a support vector machine classifier, we found
      that mothers consistently shifted their timbre between ADS and IDS. Importantly,
      this shift was similar across languages, suggesting that such alterations of
      timbre may be universal. These findings have theoretical implications for
      understanding how infants tune in to their local communicative environments.
      Moreover, our classification algorithm for identifying infant-directed timbre has
      direct translational implications for speech recognition technology.

PMID- 29033332
TI  - Disruption of Core Planar Cell Polarity Signaling Regulates Renal Tubule
      Morphogenesis but Is Not Cystogenic.
AB  - Oriented cell division (OCD) and convergent extension (CE) shape developing renal
      tubules, and their disruption has been associated with polycystic kidney disease
      (PKD) genes, the majority of which encode proteins that localize to primary
      cilia. Core planar cell polarity (PCP) signaling controls OCD and CE in other
      contexts, leading to the hypothesis that disruption of PCP signaling interferes
      with CE and/or OCD to produce PKD. Nonetheless, the contribution of PCP to
      tubulogenesis and cystogenesis is uncertain, and two major questions remain
      unanswered. Specifically, the inference that mutation of PKD genes interferes
      with PCP signaling is untested, and the importance of PCP signaling for
      cystogenic PKD phenotypes has not been examined. We show that, during
      proliferative stages, PCP signaling polarizes renal tubules to control OCD.
      However, we find that, contrary to the prevailing model, PKD mutations do not
      disrupt PCP signaling but instead act independently and in parallel with PCP
      signaling to affect OCD. Indeed, PCP signaling that is normally downregulated
      once development is completed is retained in cystic adult kidneys. Disrupting PCP
      signaling results in inaccurate control of tubule diameter, a tightly regulated
      parameter with important physiological ramifications. However, we show that
      disruption of PCP signaling is not cystogenic. Our results suggest that
      regulating tubule diameter is a key function of PCP signaling but that loss of
      this control does not induce cysts.

PMID- 29033334
TI  - Genetic Ancestry of Rapanui before and after European Contact.
AB  - The origins and lifeways of the inhabitants of Rapa Nui (Easter Island), a remote
      island in the southeast Pacific Ocean, have been debated for generations.
      Archaeological evidence substantiates the widely accepted view that the island
      was first settled by people of Polynesian origin, as late as 1200 CE [1-4]. What
      remains controversial, however, is the nature of events in the island's
      population history prior to the first historic contact with Europeans in 1722 CE.
      Purported contact between Rapa Nui and South America is particularly contentious,
      and recent studies have reported genetic evidence for Native American admixture
      in present-day indigenous inhabitants of Rapa Nui [5-8]. Statistical modeling has
      suggested that this genetic contribution might have occurred prior to European
      contact [6]. Here we directly test the hypothesis that the Native American
      admixture of the current Rapa Nui population predates the arrival of Europeans
      with a paleogenomic analysis of five individual samples excavated from Ahu Nau
      Nau, Anakena, dating to pre- and post-European contact, respectively. Complete
      mitochondrial genomes and low-coverage autosomal genomes show that the analyzed
      individuals fall within the genetic diversity of present-day and ancient
      Polynesians, and we can reject the hypothesis that any of these individuals had
      substantial Native American ancestry. Our data thus suggest that the Native
      American ancestry in contemporary Easter Islanders was not present on the island
      prior to European contact and may thus be due to events in more recent history.

PMID- 29033335
TI  - Alpha-Band Activity Reveals Spontaneous Representations of Spatial Position in
      Visual Working Memory.
AB  - An emerging view suggests that spatial position is an integral component of
      working memory (WM), such that non-spatial features are bound to locations
      regardless of whether space is relevant [1, 2]. For instance, past work has shown
      that stimulus position is spontaneously remembered when non-spatial features are
      stored. Item recognition is enhanced when memoranda appear at the same location
      where they were encoded [3-5], and accessing non-spatial information elicits
      shifts of spatial attention to the original position of the stimulus [6, 7].
      However, these findings do not establish that a persistent, active representation
      of stimulus position is maintained in WM because similar effects have also been
      documented following storage in long-term memory [8, 9]. Here we show that the
      spatial position of the memorandum is actively coded by persistent neural
      activity during a non-spatial WM task. We used a spatial encoding model in
      conjunction with electroencephalogram (EEG) measurements of oscillatory alpha
      band (8-12 Hz) activity to track active representations of spatial position. The
      position of the stimulus varied trial to trial but was wholly irrelevant to the
      tasks. We nevertheless observed active neural representations of the original
      stimulus position that persisted throughout the retention interval. Further
      experiments established that these spatial representations are dependent on the
      volitional storage of non-spatial features rather than being a lingering effect
      of sensory energy or initial encoding demands. These findings provide strong
      evidence that online spatial representations are spontaneously maintained in WM
      regardless of task relevance-during the storage of non-spatial features.

PMID- 29033336
TI  - Open Abdomen Therapy with Vacuum and Mesh Mediated Fascial Traction After Aortic
      Repair: an International Multicentre Study.
AB  - OBJECTIVES: Open abdomen therapy may be necessary to prevent or treat abdominal
      compartment syndrome (ACS). The aim of the study was to analyse the primary
      delayed fascial closure (PDFC) rate and complications after open abdomen therapy
      with vacuum and mesh mediated fascial traction (VACM) after aortic repair and to
      compare outcomes between those treated with open abdomen after primary versus
      secondary operation. METHODS: This was a retrospective cohort, multicentre study
      in Sweden, Finland, and Norway, including consecutive patients treated with open
      abdomen and VACM after aortic repair at six vascular centres in 2006-2015. The
      primary endpoint was PDFC rate. RESULTS: Among 191 patients, 155 were men. The
      median age was 71 years (IQR 66-76). Ruptured abdominal aortic aneurysm (RAAA)
      occurred in 69.1%. Endovascular/hybrid and open repairs were performed in 49 and
      142 patients, respectively. The indications for open abdomen were inability to
      close the abdomen (62%) at primary operation and ACS (80%) at secondary
      operation. Duration of open abdomen was 11 days (IQR 7-16) in 157 patients alive
      at open abdomen termination. The PDFC rate was 91.8%. Open abdomen initiated at
      primary (N=103), compared with secondary operation (N=88), was associated with
      less severe initial open abdomen status (p=.006), less intestinal ischaemia
      (p=.002), shorter duration of open abdomen (p=.007), and less renal replacement
      therapy (RRT, p<.001). In hospital mortality was 39.3%, and after entero
      atmospheric fistula (N=9) was 88.9%. Seven developed graft infection within 6
      months, 1 year mortality was 28.6%. Intestinal ischaemia (OR 3.71, 95% CI 1.55
      8.91), RRT (OR 3.62, 95% CI 1.72-7.65), and age (OR 1.12, 95% CI 1.06-1.12), were
      independent factors associated with in hospital mortality, but not open abdomen
      initiated at primary versus secondary operation. CONCLUSIONS: VACM was associated
      with a high PDFC rate after prolonged open abdomen therapy following aortic
      repair. Patient outcomes seemed better when open abdomen was initiated at
      primary, compared with secondary operation but a selection effect is possible.

PMID- 29033337
TI  - Editor's Choice - Five Year Results of Great Saphenous Vein Treatment: A Meta
      analysis.
AB  - OBJECTIVES: The most frequently used treatment options for great saphenous vein
      incompetence are high ligation with stripping (HL+S), endovenous thermal ablation
      (EVTA), mainly consisting of endovenous laser ablation (EVLA) or radiofrequency
      ablation, and ultrasound guided foam sclerotherapy (UGFS). The objective of this
      systematic review and meta-analysis was to compare the long-term efficacy of
      these different treatment modalities. METHODS: A systematic literature search was
      performed. Randomised controlled trials (RCTs) with follow-up >= 5 years were
      included. Pooled proportions of anatomical success, which was the primary
      outcome, rate of recurrent reflux at the saphenofemoral junction (SFJ), and mean
      difference in venous clinical severity score (VCSS) were compared using a z test
      or Student t test. Quality of life data were assessed and described. RESULTS:
      Three RCTs and 10 follow-up studies of RCTs were included of which 12 were pooled
      in the meta-analysis. In total, 611 legs were treated with EVLA, 549 with HL+S,
      121 with UGFS, and 114 with HL+EVLA. UGFS had significantly lower pooled
      anatomical success rates than HL+S, EVLA, and EVLA with high ligation: 34% (95%
      CI 26-44) versus 83% (95% CI 72-90), 88% (95% CI 82-92), and 88% (95% CI 17-100)
      respectively; p <= .001. The pooled recurrent reflux rate at the SFJ was
      significantly lower for HL+S than UGFS (12%, 95% CI 7-20, vs. 29%, 95% CI 21-38;
      p <= .001) and EVLA (12%, 95% CI 7-20, vs. 22%, 95% CI 14-32; p = .038). VCSS
      scores were pooled for EVLA and HL+S, which showed similar improvements.
      CONCLUSION: EVLA and HL+S show higher success rates than UGFS 5 years after GSV
      treatment. Recurrent reflux rates at the SFJ were significantly lower in HL+S
      than UGFS and EVLA. VCSS scores were similar between EVLA and HL+S.

PMID- 29033338
TI  - Antibiotic-Resistance Genes in Waste Water.
AB  - Waste water and waste water treatment plants can act as reservoirs and
      environmental suppliers of antibiotic resistance. They have also been proposed to
      be hotspots for horizontal gene transfer, enabling the spread of antibiotic
      resistance genes between different bacterial species. Waste water contains
      antibiotics, disinfectants, and metals which can form a selection pressure for
      antibiotic resistance, even in low concentrations. Our knowledge of antibiotic
      resistance in waste water has increased tremendously in the past few years with
      advances in the molecular methods available. However, there are still some gaps
      in our knowledge on the subject, such as how active is horizontal gene transfer
      in waste water and what is the role of the waste water treatment plant in the
      environmental resistome? The purpose of this review is to briefly describe some
      of the main methods for studying antibiotic resistance in waste waters and the
      latest research and main knowledge gaps on the issue. In addition, some future
      research directions are proposed.

PMID- 29033340
TI  - Nonepileptic seizure provoked by cardiac dysrhythmia with STEMI.
AB  - Acute seizures represent 1% of all visits to emergency departments in the United
      States. While many acute seizures are correctly attributable to underlying
      epilepsy, approximately one-third of acute seizures are provoked by underlying
      and potentially life-threatening acute conditions. Many clinical syndromes
      associated with seizure-like activity are well-established and readily identified
      in the acute setting. Cardiac dysrhythmias are known causes of acute seizure-like
      activity and, if transient and not captured by electrocardiogram tracings during
      acute episodes, may be incorrectly diagnosed as epileptic seizures. We report a
      case of acute ST-segment elevation myocardial infarction presenting with acute
      symptomatic seizure due to occult transient cardiac dysrhythmia.

PMID- 29033339
TI  - Transmissible Viral Vaccines.
AB  - Genetic engineering now enables the design of live viral vaccines that are
      potentially transmissible. Some designs merely modify a single viral genome to
      improve on the age-old method of attenuation whereas other designs create
      chimeras of viral genomes. Transmission has the benefit of increasing herd
      immunity above that achieved by direct vaccination alone but also increases the
      opportunity for vaccine evolution, which typically undermines vaccine utility.
      Different designs have different epidemiological consequences but also experience
      different evolution. Approaches that integrate vaccine engineering with an
      understanding of evolution and epidemiology will reap the greatest benefit from
      vaccine transmission.

PMID- 29033341
TI  - Acute intractable headache and oculomotor nerve palsy associated with nicorandil:
      A case report.
AB  - Acute non-traumatic headaches with neurological deficits alarm emergency
      department (ED) physicians. Typically, a sudden headache with oculomotor nerve
      palsy involving a pupil indicates the possibility of a subarachnoid hemorrhage
      (SAH) due to an aneurysm originating from the posterior communicating artery. For
      the ED physician, thinking beyond the possibility of an SAH can be crucial. Here,
      we report on a 59-year-old woman who presented to the ED with an intractable
      headache and right ptosis. She had previously received nicorandil for paroxysmal
      atrial fibrillation in the cardiology clinic. Her vital signs were stable upon ED
      arrival. Neurological examination revealed a mild anisocoria with a sluggish
      response to light stimuli in the right eye. Adduction, supraduction, and
      infraduction were also limited in the right eye. Nuchal rigidity was not
      apparent. An urgent brain magnetic resonance image (MRI) with angiography was
      requested to assess for possible SAH, but revealed no aneurysm. Cerebrospinal
      fluid analysis was also unremarkable. The patient's headache and oculomotor nerve
      palsy improved completely after discontinuation of nicorandil for 3 days. To the
      best of our knowledge, this is the first case report on side effects of
      nicorandil presenting as a severe headache with reversible oculomotor nerve palsy
      involving a pupil, symptoms which mimicked a possible SAH due to aneurysm.

PMID- 29033342
TI  - Intentional cyanoacrylate ingestion: A rare cause of delayed gastric perforation
      requiring gastric wedge resection.
AB  - Cyanoacrylate (LOCTITE(r) 401TM) is a fast-acting adhesive available nationwide,
      with medical and household uses. Most cases of cyanoacrylate exposure are
      accidental and occur in children less than 5years old. Various routes of exposure
      have been reported including the dermal, oral, ocular, otic, nasal, and urethral
      routes; however, very few result in serious complication and mortality. Although
      a few cases of airway obstruction related to cyanoacrylate ingestion have been
      reported, intentional cyanoacrylate ingestion-induced gastrointestinal tract
      injury has scarcely been reported. In addition, there have been no reports of
      serious complications following intentional cyanoacrylate ingestion requiring
      surgical intervention. Herein, we report a case of intentional ingestion of
      cyanoacrylate in a 70-year-old man who required gastric wedge resection due to
      delayed gastric perforation.

PMID- 29033343
TI  - Symptomatic relief as an outcome in studies of nasogastric decompression in small
      bowel obstruction.

PMID- 29033344
TI  - A prospective study of ketamine as primary therapy for prehospital profound
      agitation.
AB  - OBJECTIVE: We investigated the effectiveness of ketamine as a primary therapy for
      prehospital profound agitation. METHODS: This was a prospective observational
      study of patients receiving 5mg/kg of intramuscular ketamine for profound
      agitation, defined as a score of +4 on the Altered Mental Status Scale (AMSS), a
      validated ordinal scale of agitation from -4 (unresponsive) to +4 (most
      agitated). The primary outcome was time to adequate sedation (AMSS<+1). Secondary
      outcomes included need for additional sedatives, intubation frequency,
      complications associated with ketamine, and mortality. RESULTS: Forty-nine
      patients were enrolled. Median age was 29years (range 18-66); 76% (37/49) were
      male. Median time to adequate sedation was 4.2min (95% CI: 2.5-5.9, range 1
      25min) and 90% (44/49) had adequate sedation prehospital. Seven patients (14%)
      received a second sedative prehospital. Intubation occurred in 57% (28/49) of
      patients. Mechanical ventilation lasted <24h in 82% (23/28) of patients, and <48h
      in 96% (27/28) of patients. A single physician intubated 36% (10/28) of the
      patients. Complications related to ketamine included hypersalivation (n=9, 18%),
      vomiting (n=3, 6%), and emergence reaction (n=2, 4%). One patient died from
      complications of septic shock on hospital day 29, likely unrelated to ketamine.
      CONCLUSIONS: In patients with prehospital profound agitation, ketamine provides
      rapid effective sedation when used as a primary therapy. Intubation was common
      but accompanied by a short duration of mechanical ventilation and appears to have
      been subject to individual physician practice variation.

PMID- 29033345
TI  - Along the Colorado Trail: Assessing the average hikers' knowledge of altitude
      sickness.

PMID- 29033346
TI  - Emergency sonographers can identify and inject the flexor tendon sheaths in human
      cadaveric models.

PMID- 29033347
TI  - A multilevel stakeholder approach for identifying the determinants of
      implementation of government-funded community pharmacy services at the primary
      care level.
AB  - BACKGROUND: A key early step to enhance the integration of community pharmacy
      services (CPSs) into primary care practice is identifying key determinants of
      practice (i.e., critical circumstances that influence the implementation of such
      services). Involving relevant stakeholders in identifying key determinants
      enables findings to be more relevant to the context in which CPSs will be
      implemented. OBJECTIVE: To identify key determinants of practice that can
      influence the implementation of government-funded CPSs in a primary health
      network in Australia. METHODS: A stakeholder collaborative approach was used,
      encompassing two phases. In the first phase, semi-structured interviews were
      conducted with ground-level stakeholders in Western Sydney between August 2016 to
      October 2016. Framework analysis was used to code and analyse the data from the
      interviews into determinants of pharmacy practice. In the second phase, a
      workshop was conducted with a mixed-group of ground-level and system-level
      stakeholders from the primary health network to identify key determinants. A four
      quadrant prioritization matrix was employed in the workshop to classify
      determinants based on their importance and feasibility. RESULTS: Sixty-five
      determinants of practice that can influence CPS implementation were identified in
      Phase 1. These determinants were allocated at different levels of the healthcare
      system, and can exist as a barrier or facilitator or both. Twenty-two key
      determinants were selected in Phase 2, of which three were agreed to be addressed
      initially: (1) Patient understanding of the aims of the service; (2) Commitment
      of the organization and its leaders to provide services; (3) Coordination of the
      healthcare system to prompt collaboration between pharmacists and GPs.
      CONCLUSIONS: This collaborative stakeholder approach identified a set of key
      determinants of pharmacy practice in this Australian primary care setting. To
      enhance the implementation of CPSs in this region, initial efforts should be
      aimed at developing implementation strategies based on these key determinants of
      practice.

PMID- 29033348
TI  - Design and synthesis of benzimidazole-based Rho kinase inhibitors for the
      treatment of glaucoma.
AB  - Rho kinase inhibitors (ROCK II) play a key role in glaucoma management attributed
      to their IOP lowering ability and neuroprotective effects. In the present study,
      a series of novel benzimidazole derivatives (9a-m) has been synthesized and
      evaluated for their IOP lowering, Rho kinase inhibitory and antioxidant
      properties. The synthesized compounds were found to be lipophilic and showed a
      significant IOP lowering effect both in the treated and the contralateral eye
      comparable to the reference standard fasudil. The nitrophenyl piperazine
      substituted compound 9j exhibited significant IOP lowering (51.56%) and an
      inhibition of 57.25 and 77.92% towards ROCK II enzyme at a concentration of 0.5
      and 1 mM respectively. It possessed a considerable free radical scavenging
      activity exhibiting an IC50 value of 95.49 ug/mL in DPPH assay. The molecular
      docking studies of compound 9j indicated the binding of the compound at the
      active site of recombinant human ROCK II which makes it a promising antiglaucoma
      agent.

PMID- 29033349
TI  - A polymorphism in the glucocorticoid receptor gene is associated with refractory
      hypotension in premature infants.
AB  - BACKGROUND: Glucocorticoids play an important role in endocrine control. The
      association of glucocorticoid receptor (GR) gene polymorphisms with altered
      sensitivity to glucocorticoid therapy has been reported in adults. However, there
      are few such reports in infants. The present study analyzed the prevalence of
      four GR polymorphisms in preterm infants born before 30 weeks of gestation and
      determined the associations between these polymorphisms and clinical outcomes in
      the infants. METHODS: Totally, 41 preterm infants born at two hospitals in
      Fukushima were retrospectively screened for the presence of four GR gene
      polymorphisms, using a TaqMan single-nucleotide polymorphism genotyping assay.
      The effect of GR gene polymorphisms on clinical outcomes during hospitalization
      was evaluated. The following primary clinical outcomes were assessed: refractory
      hypotension in the acute phase and/or severe bronchopulmonary dysplasia, maximum
      dopamine and dobutamine doses administered, and total hydrocortisone dose
      administered in the first 48 h of life. Multivariate analysis with logistic
      regression was used to assess the association between clinical factors and
      refractory hypotension. RESULTS: Of the four GR polymorphisms, only the BclI
      polymorphism was detected. The genotype distribution was as follows: C/C, 33;
      C/G, 8; and G/G, 0 infants. Significant differences were observed between the C/C
      and C/G genotypes with respect to the following variables: refractory hypotension
      (6% vs. 50%), dopamine dose [3.0 (2.0-4.0) vs. 4.8 (4.0-7.5) MUg/kg/min],
      dobutamine dose [2.4 (0.0-3.6) vs. 4.0 (0-10.0) MUg/kg/min], and total
      hydrocortisone dose administered in the first 48 h of life [2.0 (0-10.0) vs. 6.0
      (0-12.0) mg/kg]. Multivariate analysis showed that the BclI genotype (C/C) was
      significantly less associated with refractory hypotension in the acute phase
      (odds ratio, 0.008; 95% confidence interval, 0.000-0.371; p = 0.013). CONCLUSION:
      The incidence of refractory hypotension in infants with the C/C genotype was
      initially expected to be higher than that in infants with the C/G genotype.
      However, the results of this study were rather different from what we originally
      expected. The suppressive effect of antenatal steroid use on the HPA axis of the
      preterm infants with the BclI variant may be associated with refractory
      hypotension in the acute phase.

PMID- 29033350
TI  - Phenotypical characterization of human rhinovirus infections in severely
      premature children.
AB  - BACKGROUND: Human Rhinovirus (HRV) has been identified as the most common cause
      of acute respiratory infections and hospitalizations in premature children. It is
      unclear if premature children are more susceptible to HRV due to their decreased
      pulmonary reserve or because they have enhanced lower airway reactivity to HRV.
      METHODS: We conducted a retrospective analysis of the clinical respiratory
      presentation of all PCR-confirmed HRV infections in full-term and premature
      children aged <=3 years in our institution. Standardized respiratory distress
      scores were developed to examine lower airway obstruction (i.e., wheezing,
      hyperinflation, and sub-costal retractions) along with markers of decreased
      pulmonary reserve (hypoxemia and tachypnea) in young children with HRV
      infections. Demographic and clinical variables were obtained from reviewing
      electronic medical records (EMR). RESULTS: This study included a total of 205
      children; 71% of these children were born full-term (>37 weeks gestation), 10%
      preterm (32-37 weeks) and 19% severely premature (<32 weeks). Our results
      demonstrated that: 1) HRV infections in the first 3 years of life were associated
      with higher overall respiratory distress scores in severely premature children
      relative to children born preterm or full-term; 2) HRV-infected severely
      premature children <=3 years old were more likely to have lower airway
      obstruction than HRV-infected children born preterm or full-term; and 3) other
      clinical signs of respiratory distress such as tachypnea and hypoxemia were not
      more common in severely premature than in preterm and full-term children during
      an HRV infection. CONCLUSIONS: Our results indicate that HRV infections in
      severely premature children are associated with lower airway obstruction rather
      than hypoxemia or tachypnea. The latter suggests that enhanced airway reactivity
      is the underlying mechanism for the increased susceptibility to HRV in severely
      premature children. Longitudinal studies are needed to understand why premature
      babies develop airway hyper-reactivity to HRV and the long-term effects of early
      HRV infection in this population.

PMID- 29033351
TI  - Mouse Cutaneous Melanoma Induced by Mutant BRaf Arises from Expansion and
      Dedifferentiation of Mature Pigmented Melanocytes.
AB  - To identify the cells at the origin of melanoma, we combined single-cell lineage
      tracing and transcriptomics approaches with time-lapse imaging. A mouse model
      that recapitulates key histopathological features of human melanomagenesis was
      created by inducing a BRafV600E-driven melanomagenic program in tail
      interfollicular melanocytes. Most targeted mature, melanin-producing melanocytes
      expanded clonally within the epidermis before losing their differentiated
      features through transcriptional reprogramming and eventually invading the
      dermis. Tumors did not form within interscales, which contain both mature and
      dormant amelanotic melanocytes. The hair follicle bulge, which contains
      melanocyte stem cells, was also refractory to melanomagenesis. These studies
      identify varying tumor susceptibilities within the melanocytic lineage,
      highlighting pigment-producing cells as the melanoma cell of origin, and indicate
      that regional variation in tumor predisposition is dictated by microenvironmental
      cues rather than intrinsic differences in cellular origin. Critically, this work
      provides in vivo evidence that differentiated somatic cells can be reprogrammed
      into cancer initiating cells.

PMID- 29033352
TI  - The Primate-Specific Gene TMEM14B Marks Outer Radial Glia Cells and Promotes
      Cortical Expansion and Folding.
AB  - Human brain evolution is associated with expansion and folding of the neocortex.
      Increased diversity in neural progenitor (NP) populations (such as basally
      located radial glia [RG], which reside in an enlarged outer subventricular zone
      [OSVZ]) likely contributes to this evolutionary expansion, although their
      characteristics and relative contributions are only partially understood. Through
      single-cell transcriptional profiling of sorted human NP subpopulations, we
      identified the primate-specific TMEM14B gene as a marker of basal RG. Expression
      of TMEM14B in embryonic NPs induces cortical thickening and gyrification in
      postnatal mice. This is accompanied by SVZ expansion, the appearance of outer RG
      like cells, and the proliferation of multiple NP subsets, with proportional
      increases in all cortical layers and normal lamination. TMEM14B drives NP
      proliferation by increasing the phosphorylation and nuclear translocation of
      IQGAP1, which in turn promotes G1/S cell cycle transitions. These data show that
      a single primate-specific gene can drive neurodevelopmental changes that
      contribute to brain evolution.

PMID- 29033354
TI  - Confronting the misbeliefs pertaining to blood donation and transfusion practices
      in India.

PMID- 29033353
TI  - Melanocyte Stem Cell Activation and Translocation Initiate Cutaneous Melanoma in
      Response to UV Exposure.
AB  - Melanoma is one of the deadliest cancers, yet the cells of origin and mechanisms
      of tumor initiation remain unclear. The majority of melanomas emerge from clear
      skin without a precursor lesion, but it is unknown whether these melanomas can
      arise from melanocyte stem cells (MCSCs). Here we employ mouse models to define
      the role of MCSCs as melanoma cells of origin, demonstrate that MCSC quiescence
      acts as a tumor suppressor, and identify the extrinsic environmental and
      molecular factors required for the critical early steps of melanoma initiation.
      Specifically, melanomas originate from melanoma-competent MCSCs upon stimulation
      by UVB, which induces MCSC activation and translocation via an inflammation
      dependent process. Moreover, the chromatin-remodeling factor Hmga2 in the skin
      plays a critical role in UVB-mediated melanomagenesis. These findings delineate
      melanoma formation from melanoma-competent MCSCs following extrinsic stimuli, and
      they suggest that abrogation of Hmga2 function in the microenvironment can
      suppress MCSC-originating cutaneous melanomas.

PMID- 29033355
TI  - Evaluation of the effect of serratus anterior plane block for pain treatment
      after video-assisted thoracoscopic surgery.
AB  - BACKGROUND: Analgesia following video-assisted thoracoscopic surgery (VATS) is
      important for the prevention of postoperative pulmonary complications. Various
      regional methods of anaesthesia are currently being used to achieve this goal. In
      our study, we aim to assess the effectiveness of SAPB on postoperative VATS
      analgesia in our study. METHODS: A total of 40 patients aged between 18 and 70
      years, those who were in the Society of Anaesthesiologists (ASA) I-III class and
      underwent VATS were included in the study. Patients were randomised to either
      group T (intravenous patient-controlled analgesia tramadol; n=20) or group S
      (intravenous patient-controlled analgesia tramadol+SAPB; n=20). Visual Analogue
      Scale (VAS) was used for postoperative pain, the primary outcome measure, were
      evaluated at post-anaesthetic care unit (PACU), 2, 6, 12, and 24 hours. Secondary
      outcomes included the postoperative 2nd, 6th, 12th, and 24th hour follow-up
      results were evaluated to identify the quantity of tramadol use, Ramsay sedation
      scale (RSS), side effect profile, and additional analgesic use. RESULTS: The VAS
      scores between the two groups were found to be statistically significantly lower
      in group S during the PACU observation (P<0.05). The mean values of the quantity
      of tramadol use at the 6th, 12th, and 24th hours were found to be statistically
      significantly lower in group S (P<0.05). There was no statistically significant
      difference in the rate of side effects and RSS outcomes between the groups
      (P>0.05). CONCLUSIONS: Our study results suggest that SAPB is an effective
      treatment option for VATS analgesia.

PMID- 29033356
TI  - Benefits of intraoperative analgesia guided by the Analgesia Nociception Index
      (ANI) in bariatric surgery: An unmatched case-control study.
AB  - INTRODUCTION: Analgesia Nociception Index (ANI) has been proposed for the
      evaluation of the nociception-antinociception balance in the perioperative
      period. In obese patients, where the management of analgesia may be rendered
      difficult by pharmacological changes, we hypothesised that the monitoring of
      analgesia with ANI would reduce intraoperative opioid consumption during
      bariatric surgery. METHODS: This monocentric, observational, unmatched case
      control study aimed to compare perioperative data from obese subjects (body mass
      index >=35kgm-2) during bariatric surgery with or without the use of ANI
      monitoring (ANI+ group versus ANI- group). Intraoperative analgesia was provided
      by injection of sufentanil, which was performed according to the clinician's
      assessment in the ANI- group or to the ANI value in the ANI+ group. The primary
      outcome was the mean hourly intraoperative sufentanil requirement. Secondary
      outcomes included the need for postoperative morphine titration, incidence of
      nausea and vomiting, respiratory distress and pain scores in the first 24hours.
      RESULTS: Between December 2013 and September 2016, 60 obese patients (i.e. 30 per
      group) were included. The mean hourly consumption of sufentanil was significantly
      lower in the ANI+ group (0.15+/-0.05MUgkg-1h-1 versus 0.17+/-0.05MUgkg-1h-1,
      P=0.038). We found no difference between groups regarding the incidence of nausea
      and vomiting, acute respiratory distress, the need for postoperative morphine
      titration, or pain scores in the first 24 postoperative hours. CONCLUSION: The
      use of ANI monitoring might reduce intraoperative consumption of sufentanil
      during bariatric surgery but does not appear to be accompanied by a reduction in
      its side effects.

PMID- 29033357
TI  - A history of community-acquired hypervirulent Klebsiella pneumoniae severe
      sepsis.

PMID- 29033358
TI  - Predictive factors of early postoperative respiratory complications after
      tonsillectomy in children with unidentified risks for this complication.
AB  - INTRODUCTION: Tonsillectomy is considered as a therapeutic option in obstructive
      sleep apnoea syndrome (OSAS). Postoperative respiratory failure is a complication
      that can require respiratory support. The main objective of our study is to
      determine risk factors of postoperative respiratory complications in children
      undergoing tonsillectomy. MATERIAL AND METHODS: This is a retrospective single
      centre observational study including patients with unanticipated postoperative
      respiratory failure. Patients with a planned preoperative intensive care
      admission were excluded (age is lower than 2 years, overweight (>95% percentile
      of BMI), moderate or severe asthma, major medical conditions). Those patients
      were compared with randomly selected control patients. Factors studied were: age,
      weight, indication of surgery, ASA status, preoperative illness conditions,
      durations of surgery and anaesthesia and administered medications. Statistics
      used a univariate analysis and a multivariate logistic regression. RESULTS: Eight
      hundred and five patients underwent adenotonsillectomy during the study period
      and 25 developed postoperative respiratory failure. These patients were compared
      to 103 non-complicated control patients. Age (<4 years), weight (<18kg),
      indication of surgery (as SOAS), laryngomalacia, stable and minor congenital
      cardiac malformation and duration of anaesthesia were found statistically
      associated. Multivariate analysis found that weight <18kg is a risk factor
      associated with the occurrence of postoperative respiratory failure. Overall the
      model shows a strong accuracy with an area under the curve of ROC analysis of 0.9
      [95% confidence interval: 0.85-0.95]. DISCUSSION: Our study found that weight
      <18kg is a major risk factor for predicting a postoperative respiratory
      complication.

PMID- 29033359
TI  - Immediate postoperative plasma neutrophil gelatinase-associated lipocalin to
      predict acute kidney injury after major open abdominal aortic surgery: A
      prospective observational study.
AB  - INTRODUCTION: Plasma neutrophil gelatinase-associated lipocalin (pNGAL) has been
      used as a biomarker in acute kidney injury (AKI). AKI is a common postoperative
      complication of aortic surgery. We sought to evaluate the performance of the
      immediately postoperative pNGAL level in comparison with the serum creatinine
      (SCr) level in predicting AKI and the need for renal replacement therapy (RRT).
      PATIENTS AND METHODS: Prospective non-interventional study in a university
      hospital. Fifty patients undergoing elective or emergent major intra-abdominal
      aortic surgery were included. Comparisons between groups of patients with or
      without postoperative AKI, according to KDIGO staging, were made. Performance of
      NGAL was determined by examining the area under receiver operating characteristic
      (AUROC) curve. RESULTS: The incidence of AKI was 36%. At H+2, pNGAL values in AKI
      and non-AKI patients, respectively, were 221 [133-278] versus 50 [50-90] ng/mL
      (P<0.0001), and SCr values were 115 [96-178] versus 90 [72-99] MUmol/L
      (P<0.0008). The AUROC of pNGAL for prediction of AKI was 0.90 (95% CI: 0.81-0.98)
      with an optimal cutoff of 112ng/mL, a sensitivity of 83%, specificity of 84%, and
      positive and negative predictive values of 75% and 90%, respectively. SCr
      produced an AUROC curve of 0.79 (0.65-0.92) at a cutoff of 110MUmol/L. The
      diagnostic performance of pNGAL was significantly better than that of SCr
      (P=0.039). PNGAL at H+2 better predicted the RRT requirement [0.96 (0.90-1.0)]
      compared to SCr [0.86 (0.73-0.98)], but this difference was not statistically
      significant. CONCLUSIONS: A 2-hour postoperative determination of pNGAL
      outperformed SCr level in predicting postoperative AKI after major aortic
      surgery.

PMID- 29033360
TI  - Veno-arterial-ECMO in the intensive care unit: From technical aspects to clinical
      practice.
AB  - The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as a
      salvage therapy in cardiogenic shock is becoming of current practice. While VA
      ECMO is potentially a life-saving technique, results are sometimes mitigated,
      emphasising the need for selecting the right indication in the right patient.
      This relies upon a clear definition of the individual therapeutic project,
      including the potential for recovery as well as the possible complications
      associated with VA-ECMO. To maximise the benefits of VA-ECMO, the basics of
      extracorporeal circulation should be perfectly understood since VA-ECMO can
      sometimes be detrimental. Hence, to be successful, VA-ECMO should be used by
      teams with sufficient experience and initiated after a thorough multidisciplinary
      discussion considering patient's medical history, pathology as well the
      anticipated evolution of the disease.

PMID- 29033363
TI  - Convergent Transcriptional Programs Regulate cAMP Levels in C. elegans GABAergic
      Motor Neurons.
AB  - Both transcriptional regulation and signaling pathways play crucial roles in
      neuronal differentiation and plasticity. Caenorhabditis elegans possesses 19
      GABAergic motor neurons (MNs) called D MNs, which are divided into two subgroups:
      DD and VD. DD, but not VD, MNs reverse their cellular polarity in a developmental
      process called respecification. UNC-30 and UNC-55 are two critical transcription
      factors in D MNs. By using chromatin immunoprecipitation with CRISPR/Cas9 knockin
      of GFP fusion, we uncovered the global targets of UNC-30 and UNC-55. UNC-30 and
      UNC-55 are largely converged to regulate over 1,300 noncoding and coding genes,
      and genes in multiple biological processes, including cAMP metabolism, are co
      regulated. Increase in cAMP levels may serve as a timing signal for
      respecification, whereas UNC-55 regulates genes such as pde-4 to keep the cAMP
      levels low in VD. Other genes modulating DD respecification such as lin-14, irx
      1, and oig-1 are also found to affect cAMP levels.

PMID- 29033364
TI  - [Recurrent cystisis: No medicine preventive means].
AB  - OBJECTIVE: To estimate from the literature review, the interest of hygienic and
      behavioural measures and the use of food supplements (herbal) to prevent female
      urinary tract infection. METHODS: Pubmed research was focused on the efficiency
      of prophylactic measures in recurrent cystisis management. RESULTS: Due to many
      predisposing factors such as anatomical charasteristics, hydration and lifestyle,
      cystisis is more common in female subjects than in male. The infection is mostly
      caused by uropathgenic Escherichia coli which is mostly found in the intestine.
      Recomendations propose a better use of antibiotics that causes undesirable side
      effects (such as nausea, candidiasis) and favours the development of resistant
      bacterial strains. Hygienic measures, good hydration, and respecting a good
      urinary rythm help to protect from new infectious episodes. Food supplements such
      as cranberry or D-mannose can also interfere with the recurrence of cystisis, by
      preventing the bacteria sticking to urinary tract epithelia. Their efficency is
      relative and seems to be dose-dependent. Better tolerated than prophylactic
      antibiotic treatments, they can increase times of respite. CONCLUSION: Using
      prophylactic treatment still have an interest, even if they are questionable.
      Moreover, the combination of these methods (diet and lifestyle advice) can be an
      alternative to long-term prophylactic medical treatment.

PMID- 29033362
TI  - An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen
      Signaling Determines Cell Fate.
AB  - Cell-cell contact formation constitutes an essential step in evolution, leading
      to the differentiation of specialized cell types. However, remarkably little is
      known about whether and how the interplay between contact formation and fate
      specification affects development. Here, we identify a positive feedback loop
      between cell-cell contact duration, morphogen signaling, and mesendoderm cell
      fate specification during zebrafish gastrulation. We show that long-lasting cell
      cell contacts enhance the competence of prechordal plate (ppl) progenitor cells
      to respond to Nodal signaling, required for ppl cell-fate specification. We
      further show that Nodal signaling promotes ppl cell-cell contact duration,
      generating a positive feedback loop between ppl cell-cell contact duration and
      cell-fate specification. Finally, by combining mathematical modeling and
      experimentation, we show that this feedback determines whether anterior axial
      mesendoderm cells become ppl or, instead, turn into endoderm. Thus, the
      interdependent activities of cell-cell signaling and contact formation control
      fate diversification within the developing embryo.

PMID- 29033366
TI  - The Bermuda triangle: Chronic kidney disease, contrast-induced nephropathy, and
      atrial fibrillation.

PMID- 29033365
TI  - Laser procedure for female urinary stress incontinence: A review of the
      literature.
AB  - INTRODUCTION: There is increasing interest in noninvasive treatment of female
      stress urinary incontinence (SUI), including a vaginal laser procedure. In view
      of a lack of data on this technique, we conducted a non-systematic review of the
      literature. METHODS: We reviewed studies concerning the laser treatment of SUI
      from PubMed, Medline, the Cochrane Library and Web of Science. Study design,
      outcome measure, number of participants, procedural complications and results
      were analyzed. RESULTS: The use of laser treatment of female SUI has been
      described in 7 prospective, single-center and non-comparative (no control group)
      studies, all of which used an erbium YAG or a CO2 laser in thermal non-ablative
      treatment. Primary outcome was ICIQ-UI-SF score in six studies, and pad tests in
      one study. Follow-up ranged from 5 to 36months. Improvement rates ranged from 62%
      to 78%. No major adverse events were noted. Minor side effects included sensation
      of warmth, increased vaginal discharge and transient urge urinary incontinence.
      CONCLUSION: The efficacy of vaginal laser treatment of SUI has not been assessed
      in comparative studies. More rigorous and adequately powered trials are required
      to assess the relative benefits and adverse event profile of laser treatment of
      SUI, as compared with other minimally invasive procedures.

PMID- 29033361
TI  - Binding of PLD2-Generated Phosphatidic Acid to KIF5B Promotes MT1-MMP Surface
      Trafficking and Lung Metastasis of Mouse Breast Cancer Cells.
AB  - Little is known about the cellular events promoting metastasis. We show that
      knockout of phospholipase D2 (PLD2), which generates the signaling lipid
      phosphatidic acid (PA), inhibits lung metastases in the mammary tumor virus
      (MMTV)-Neu transgenic mouse breast cancer model. PLD2 promotes local invasion
      through the regulation of the plasma membrane targeting of MT1-MMP and its
      associated invadopodia. A liposome pull-down screen identifies KIF5B, the heavy
      chain of the motor protein kinesin-1, as a new PA-binding protein. In vitro
      assays reveal that PA specifically and directly binds to the C terminus of KIF5B.
      The binding between PLD2-generated PA and KIF5B is required for the vesicular
      association of KIF5B, surface localization of MT1-MMP, invadopodia, and invasion
      in cancer cells. Taken together, these results identify a role of PLD2-generated
      PA in the regulation of kinesin-1 motor functions and breast cancer metastasis
      and suggest PLD2 as a potential therapeutic target for metastatic breast cancer.

PMID- 29033367
TI  - Stent implantation and vascular healing of a spontaneous coronary artery
      dissection assessed by optical coherence tomography in a patient with acute
      coronary syndrome.
AB  - A 60-year old woman with non-ST-segment elevation myocardial infarction,
      underwent coronary angiogram combined with optical coherence tomography (OCT)
      revealing a long dissection in the right coronary artery. The patient experienced
      peri-procedural chest pain, the electrocardiogram showed ST-segment elevations,
      and compromised coronary blood flow, why mechanical revascularization with
      percutaneous coronary intervention (PCI) was indicated. At 1-month follow-up, OCT
      revealed early, competent vascular healing, and a distal stenosis was treated
      with PCI. The patient has been asymptomatic since the procedure for three years.

PMID- 29033368
TI  - A DNA Vaccine Protects Human Immune Cells against Zika Virus Infection in
      Humanized Mice.
AB  - A DNA vaccine encoding prM and E protein has been shown to induce protection
      against Zika virus (ZIKV) infection in mice and monkeys. However, its
      effectiveness in humans remains undefined. Moreover, identification of which
      immune cell types are specifically infected in humans is unclear. We show that
      human myeloid cells and B cells are primary targets of ZIKV in humanized mice. We
      also show that a DNA vaccine encoding full length prM and E protein protects
      humanized mice from ZIKV infection. Following administration of the DNA vaccine,
      humanized DRAG mice developed antibodies targeting ZIKV as measured by ELISA and
      neutralization assays. Moreover, following ZIKV challenge, vaccinated animals
      presented virtually no detectable virus in human cells and in serum, whereas
      unvaccinated animals displayed robust infection, as measured by qRT-PCR. Our
      results utilizing humanized mice show potential efficacy for a targeted DNA
      vaccine against ZIKV in humans.

PMID- 29033369
TI  - Fecal Clostridium symbiosum for Noninvasive Detection of Early and Advanced
      Colorectal Cancer: Test and Validation Studies.
AB  - OBJECTIVE: Current non-invasive early detection of colorectal cancer (CRC)
      requires improvement. We aimed to identified a fecal Clostridium symbiosum-based
      biomarker for early and advanced colorectal cancer detection. DESIGN: In the test
      stage, the relative abundance of Clostridium symbiosum (C. symbiosum) was
      measured by qPCR in 781 cases including 242 controls, 212 colorectal adenoma
      (CRA) patients, 109 early CRC (tumor restricted to the submucosa) patients, 218
      advanced CRC patients. The prediction accuracy was compared to Fusobacterium
      nucleatum (F. nucleatum), fecal immunochemical test (FIT) and CEA
      (carcinoembryonic antigen) and validated in an independent cohort of 256
      subjects. Current status of the trial:ongoing/still enrolling. Primary
      endpoint:June, 2017 (Clinicaltrials.gov Identifier NCT02845973). RESULTS:
      Significant stepwise increase of C. symbiosum abundance was found in CRA, early
      CRC and advanced CRC (P<0.01). C. symbiosum outperformed all the other markers in
      early CRC prediction performance. The combination of C. symbiosum and FIT
      achieved better performance (0.803 for test cohort and 0.707 for validation
      cohort). For overall discrimination of CRCs, the combination of all above markers
      achieved the performance of 0.876. CONCLUSIONS: Fecal C. symbiosum is a promising
      biomarker for early and noninvasive detection of colorectal cancer, being more
      effective than F. nucleatum, FIT and CEA. Combining C. symbiosum and FIT or CEA
      may improve the diagnosis power.

PMID- 29033370
TI  - d-Ribose as a Contributor to Glycated Haemoglobin.
AB  - Glycated haemoglobin (HbA1c) is the most important marker of hyperglycaemia in
      diabetes mellitus. We show that d-ribose reacts with haemoglobin, thus yielding
      HbA1c. Using mass spectrometry, we detected glycation of haemoglobin with d
      ribose produces 10 carboxylmethyllysines (CMLs). The first-order rate constant of
      fructosamine formation for d-ribose was approximately 60 times higher than that
      for d-glucose at the initial stage. Zucker Diabetic Fatty (ZDF) rat, a common
      model for type 2 diabetes mellitus (T2DM), had high levels of d-ribose and HbA1c,
      accompanied by a decrease of transketolase (TK) in the liver. The administration
      of benfotiamine, an activator of TK, significantly decreased d-ribose followed by
      a decline in HbA1c. In clinical investigation, T2DM patients with high HbA1c had
      a high level of urine d-ribose, though the level of their urine d-glucose was
      low. That is, d-ribose contributes to HbA1c, which prompts future studies to
      further explore whether d-ribose plays a role in the pathophysiological mechanism
      of T2DM.

PMID- 29033371
TI  - A Small Molecule Inhibitor of the beta-Catenin-TCF4 Interaction Suppresses
      Colorectal Cancer Growth In Vitro and In Vivo.
AB  - Colorectal cancer is associated with aberrant activation of the Wnt pathway. beta
      Catenin plays essential roles in the Wnt pathway by interacting with T-cell
      factor 4 (TCF4) to transcribe oncogenes. We synthesized a small molecule,
      referred to as HI-B1, and evaluated signaling changes and biological consequences
      induced by the compound. HI-B1 inhibited beta-catenin/TCF4 luciferase activity
      and preferentially caused apoptosis of cancer cells in which the survival is
      dependent on beta-catenin. The formation of the beta-catenin/TCF4 complex was
      disrupted by HI-B1 due to the direct interaction of HI-B1 with beta-catenin.
      Colon cancer patient-derived xenograft (PDX) studies showed that a tumor with
      higher levels of beta-catenin expression was more sensitive to HI-B1 treatment,
      compared to a tumor with lower expression levels of beta-catenin. The different
      sensitivities of PDX tumors to HI-B1 were dependent on the beta-catenin
      expression level and potentially could be further exploited for biomarker
      development and therapeutic applications against colon cancer.

PMID- 29033372
TI  - Chloroquine, a FDA-approved Drug, Prevents Zika Virus Infection and its
      Associated Congenital Microcephaly in Mice.
AB  - Zika virus (ZIKV) has become a global public health emergency due to its rapidly
      expanding range and its ability to cause severe congenital defects such as
      microcephaly. However, there are no FDA-approved therapies or vaccines against
      ZIKV infection. Through our screening of viral entry inhibitors, we found that
      chloroquine (CQ), a commonly used antimalarial and a FDA-approved drug that has
      also been repurposed against other pathogens, could significantly inhibit ZIKV
      infection in vitro, by blocking virus internalization. We also demonstrated that
      CQ attenuates ZIKV-associated morbidity and mortality in mice. Finally, we proved
      that CQ protects fetal mice from microcephaly caused by ZIKV infection. Our
      methodology of focusing on previously identified antivirals in screens for
      effectiveness against ZIKV proved to be a rapid and efficient means of
      discovering new ZIKV therapeutics. Selecting drugs that were previously FDA
      approved, such as CQ, also improves the likelihood that they may more quickly
      reach stages of clinical testing and use by the public.

PMID- 29033374
TI  - Influence of visual impairment and hearing impairment on functional dependence
      status among people in Taiwan-An evaluation using the WHODAS 2.0 score.
AB  - BACKGROUND: Visual impairment (VI) and hearing impairment (HI) are the two most
      common types of sensory disability encountered clinically. However, VI and HI
      result in different limitations in daily life. We assessed the level of
      functioning in patients with VI or HI based on the International Classification
      of Functioning, Disability, and Health. METHODS: This nationwide, cross-sectional
      study included 312 people with VI and 540 people with HI. Each participant's
      degree of functioning and disability was evaluated using the World Health
      Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). The standardized
      WHODAS 2.0 scores ranged from 0 (least difficulty) to 100 (most difficulty).
      RESULTS: Patients with VI and those with HI had a mean (+/-standard error) 32
      item WHODAS 2.0 score of 42.4 +/- 2.9 and 27.1 +/- 1.6, respectively. The degree
      of restriction was positively related to the level of VI. Specifically, the
      patients with VI and a WHODAS 2.0 score of 33.7-35.3 or higher were likely to
      experience barriers to accessing mobility products, communication products, and
      education products. Furthermore, patients with a score of 42.9 or higher might
      experience barriers to accessing ingestion products and living products.
      CONCLUSION: WHODAS 2.0 scores are strongly correlated with the severity of VI.
      Mild VI should be targeted for treatment and referral as early as possible.
      Compared with the patients with HI, the patients with VI more frequently
      experience barriers to accessing environmental factors.

PMID- 29033375
TI  - Intraprocedural arterial perforation during neuroendovascular therapy:
      Preliminary result of a dual-trained endovascular neurosurgeon in the
      neurosurgical hybrid operating room.
AB  - BACKGROUND: Intraprocedural arterial perforation (IPAP) is a potentially dismal
      complication of neuroendovascular therapy with high mortality and morbidity
      rates. The management of IPAP with the techniques described has been well
      established, but rescue results from the dual-trained endovascular neurosurgeon
      in the neurosurgical hybrid operating room (OR) are rarely reported. Here, we
      report five cases of successful rescue of IPAP in the neurosurgical hybrid OR and
      compare them with other series. METHODS: Between December 2009 and December 2013,
      146 intracranial neuroendovascular procedures were performed in the hybrid
      operating room of Taichung Veterans General Hospital. A total of five patients
      with IPAP were identified. Postoperative clinical outcome was evaluated by
      Glasgow Coma Scale scores and postoperative 3-month modified Rankin Scale.
      RESULTS: The causes of the IPAP were coil protrusion (n = 3), microcatheter
      perforation (n = 1), and microwire penetration (n = 1). Two cases involved
      emergent ruptured aneurysms, while three cases occurred during elective
      procedures. Salvage treatment with emergent external ventricular drainage (EVD)
      was applied in all five cases. The average time-to-first-EVD was 16.25 min, and
      the average time-to-patent-EVD was 32.5 min. Postoperative 3-month outcome was
      good recovery (mRS <= 2) in all five cases. The zero mortality rate in our series
      is the most encouraging result in the published literature. CONCLUSION: IPAP can
      be rescued successfully with an aggressive approach and quick conversion to
      backup surgery by a dual-trained endovascular neurosurgeon in the hybrid OR. The
      value of the hybrid OR in neuroendovascular therapy should be further
      investigated in the future.

PMID- 29033373
TI  - Evaluating the Causal Link Between Malaria Infection and Endemic Burkitt Lymphoma
      in Northern Uganda: A Mendelian Randomization Study.
AB  - BACKGROUND: Plasmodium falciparum (Pf) malaria infection is suspected to cause
      endemic Burkitt Lymphoma (eBL), but the evidence remains unsettled. An inverse
      relationship between sickle cell trait (SCT) and eBL, which supports that between
      malaria and eBL, has been reported before, but in small studies with low power.
      We investigated this hypothesis in children in a population-based study in
      northern Uganda using Mendelian Randomization. METHODS: Malaria-related
      polymorphisms (SCT, IL10, IL1A, CD36, SEMA3C, and IFNAR1) were genotyped in 202
      eBL cases and 624 controls enrolled during 2010-2015. We modeled associations
      between genotypes and eBL or malaria using logistic regression. FINDINGS: SCT was
      associated with decreased risk of eBL (adjusted odds ratio [OR] 0.37, 95% CI 0.21
      0.66; p=0.0003). Decreased risk of eBL was associated with IL10 rs1800896-CT (OR
      0.73, 95% CI 0.50-1.07) and -CC genotypes (OR 0.53, 95% CI 0.29-0.95,
      ptrend=0.019); IL1A rs2856838-AG (OR 0.56, 95% CI 0.39-0.81) and -AA genotype (OR
      0.50, 95% CI 0.28-1.01, ptrend=0.0016); and SEMA3C rs4461841-CT or -CC genotypes
      (OR 0.57, 95% CI 0.35-0.93, p=0.0193). SCT and IL10 rs1800896, IL1A rs2856838,
      but not SEMA3C rs4461841, polymorphisms were associated with decreased risk of
      malaria in the controls. INTERPRETATION: Our results support a causal effect of
      malaria infection on eBL.

PMID- 29033376
TI  - Evolution of Prophylaxis Protocols for Venous Thromboembolism in Neurosurgery:
      Results from a Prospective Comparative Study on Low-Molecular-Weight Heparin,
      Elastic Stockings, and Intermittent Pneumatic Compression Devices.
AB  - BACKGROUND: The incidence of venous thromboembolism (VT) in neurosurgical
      practice is astonishingly high, representing a major cause of morbidity and
      mortality. Prophylaxis strategies include elastic stockings, low-molecular-weight
      heparin (LMWH), and intermittent pneumatic compression (IPC) devices. OBJECTIVE:
      To assess the safety and efficacy of 2 different VT prophylaxis protocols
      implemented in a European neurosurgical center. METHODS: All patients admitted
      for neurosurgical intervention between 2012 and 2016 were stratified as low,
      moderate, and high risk of VT and received a combination of elastic stockings and
      LMWH. The protocol was modified in 2014 with the inclusion of perioperative IPC
      devices for all patients and only in the high-risk group also postoperatively.
      RESULTS: At time of post-hoc analysis, data obtained from patients included in
      this study before 2014 (Protocol A, 3169 patients) were compared with those
      obtained after the introduction of IPC (Protocol B, 3818 patients). Among
      patients assigned to protocol A, 73 (2.3%) developed deep-vein thrombosis (DVT)
      and 28 (0.9%) developed pulmonary embolism (PE), 9 of which were fatal (0.3%).
      Among patients assigned to protocol B, 32 developed DVT (0.8%) and 7 (0.18%)
      developed PE, with 2 eventually resulting in the death of the patient. A post-hoc
      analysis confirmed that the use of preoperative LMWH was not associated with a
      statistically significant greater risk of postoperative bleeding. CONCLUSIONS:
      This study, despite its limitations of the nonrandomized design, seems to suggest
      that perioperative IPC devices are a non-negligible support in the prophylaxis of
      clinically symptomatic DVT and PE.

PMID- 29033377
TI  - Proposed Treatment Paradigm for Intracranial Chondrosarcomas Based on
      Multidisciplinary Coordination.
AB  - OBJECTIVES: There was no consensus regarding the treatment of intracranial
      chondrosarcoma (CSA). The study aimed to evaluate the adverse factors for
      progression-free survival (PFS) and overall survival (OS) and to propose a
      treatment strategy for CSA. METHODS: The clinical chart and radiographic data of
      106 consecutive cases (mesenchymal and conventional CSA in 18 and 88 patients,
      respectively) of surgically treated CSAs were retrospectively reviewed. RESULTS:
      Gross total resection was achieved in 43 patients (40.6%), and adjuvant
      radiotherapy was administered in 45 patients. After a mean follow-up duration of
      47.8 months, 38 patients (37.3%) experienced recurrence. PFS and disease-specific
      OS at 5 years was 57.7% and 74.4%. Independent adverse factors for PFS were
      previous surgery (hazard ratio [HR] 2.261; P = 0.028), increased lesion size (HR,
      1.298; P = 0.026), extent of surgical resection (HR, 3.226; P < 0.001), malignant
      pathology (HR, 2.018; P = 0.003), and postoperative radiotherapy (HR, 3.246; P =
      0.001). The stereotactic radiosurgery subgroup presented best 5-year PFS of
      88.9%, and a linear accelerator prolonged the mean PFS time (57.0 months)
      compared with no radiation (38.1 months). In the incomplete resection subgroup (n
      = 63), radiotherapy significantly benefited tumor control (HR, 2.101; P = 0.016).
      Extent of surgical resection (HR, 1.797; P = 0.026) and malignant disease (HR,
      1.717; P = 0.030) were associated with OS. CONCLUSIONS: Intracranial CSAs were
      not completely amendable by surgery alone. Gross total resection as far as
      possible plus radiation were necessary for mesenchymal CSA and conventional CSA
      with active growth or residual tumor. Stereotactic radiosurgery was an
      alternative if proton therapy was unavailable. A future study with a large cohort
      is required to verify our findings.

PMID- 29033378
TI  - Citizens Urge U.S. Food and Drug Administration to Restrict High-Potency Opioids.

PMID- 29033379
TI  - Is Vertebral Column Resection Necessary in Correcting Severe and Rigid Thoracic
      Kyphoscoliosis? A Single-Institution Surgical Experience.
AB  - BACKGROUND: Three-column spinal osteotomies were developed to address severe and
      stiff kyphoscoliosis. However, the optimal choice of osteotomy in these patients
      is still unclear. This retrospective study aims to compare the outcomes and
      complications between grade 4 and grade 5 osteotomies in patients with severe and
      stiff thoracic kyphoscoliosis. METHODS: Forty-five patients with severe and stiff
      thoracic kyphoscoliosis who underwent 3-column osteotomy in the thoracic spine
      were classified into 2 groups according to the grade of osteotomy. The clinical
      data and radiologic parameters were collected and compared. RESULTS: Fourteen
      patients received grade 4 osteotomy, and 31 patients received grade 5 osteotomy.
      The spinal column shortening distances were similar between groups. The
      postoperative and latest follow-up radiologic parameters were not statistically
      significant between groups. Postoperative and follow-up results demonstrated
      greater correction of the regional kyphosis angle in the grade 4 osteotomy group,
      but did not reach significant level. The operative time and blood loss of grade 5
      osteotomies were greater than those of grade 4, but showed no significant
      differences. Perioperative complication rates were also similar between groups.
      CONCLUSIONS: Similar clinical outcomes can be achieved with grade 4 and grade 5
      spinal osteotomies. This may enrich the basis on moving down to a lower osteotomy
      grade when treating patients with severe and rigid thoracic kyphoscoliosis.

PMID- 29033380
TI  - CD105 is regulated by hsa-miR-1287 and its expression is inversely correlated
      with osteopotential in SHED.
AB  - A more accurate understanding of the molecular mechanisms and signaling pathways
      underpinning human mesenchymal stem cell (MSC) plasticity and differentiation
      properties is pivotal for accomplishing solid and diligent translation of MSC
      based experimental therapeutics and clinical trials to broad clinical practice.
      In addition, this knowledge enables selection of MSC subpopulations with
      increased differentiation potential and/or use of exogenous factors to boost this
      potential. Here, we report that CD105 (ENG) is a predictive biomarker of
      osteogenic potential in two types of MSCs: stem cells from human exfoliated
      deciduous teeth (SHED) and human adipose-derived stem cells (hASC). We also
      validate that CD105 can be used to select and enrich for subpopulations of SHED
      and hASC with higher in vitro osteogenic potential. In addition, we show that hsa
      mir-1287 regulates CD105 expression, and propose that fine-tuning hsa-mir-1287
      levels could be used to control osteopotential in SHED. These findings provide
      better discernment of the molecular bases behind MSC osteogenic plasticity and
      open up new perspectives to leverage osteogenic potential in MSCs by modulation
      of a specific miRNA.

PMID- 29033381
TI  - The effect of once-yearly zoledronic acid on hip structural and biomechanical
      properties derived using computed tomography (CT) in Japanese women with
      osteoporosis.
AB  - The effects of zoledronic acid on hip structural and biomechanical properties
      were evaluated in Japanese patients with osteoporosis by computed tomography
      (CT). The subjects included in this study were a subset of female subjects
      (zoledronic acid group, 49 subjects; placebo group, 53 subjects) in the phase 3
      trial (ZONE study) who were available for multi-detector row CT (MDCT) scanning.
      Eligible subjects were those diagnosed with primary osteoporosis based on the
      Diagnostic Criteria for Primary Osteoporosis (2000) by the Japanese Society for
      Bone and Mineral Research and who had between one and four fractured vertebrae
      located between the fourth thoracic vertebra and the fourth lumbar vertebra. The
      subjects received a once-yearly intravenous infusion of zoledronic acid 5mg or
      placebo for two years. CT data were obtained at baseline and at 12 and 24months
      later and analyzed under blinded conditions. The results demonstrated that once
      yearly intravenous infusion of zoledronic acid improved volumetric bone mineral
      density (vBMD), cortical bone geometry parameters, and CT-derived biomechanical
      parameters at the femoral neck, intertrochanteric region, and shaft; particularly
      at the intertrochanteric region, significant improvements in cortical bone
      geometry parameters and CT-derived biomechanical parameters, compared with those
      in the placebo group, were detectable early, at 12months. The present data
      suggest that zoledronic acid has a possibility to reduce the risk of hip
      fractures in Japanese patients with osteoporosis.

PMID- 29033382
TI  - Clinical-pathological correlations in three patients with fibrodysplasia
      ossificans progressiva.
AB  - OBJECTIVE: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic
      disorder in which heterotopic bone forms in the soft tissues. This often occurs
      in response to injury or inflammation, leading to joint immobilization and
      significant disability. There are currently no definitive treatment options for
      this devastating disease. Although the most dramatic phenotype in FOP is the
      episodic and progressive heterotopic ossification, patients report a number of
      symptoms that affect other organ systems. Post-mortem examination of FOP patients
      may contribute to our understanding of the underlying pathophysiology and
      complications of this disease. Here, we present the autopsy findings from three
      patients with FOP. FINDINGS: Autopsy findings in two of the three patients
      confirmed that the cause of death was cardiorespiratory failure in the setting of
      severe thoracic insufficiency from heterotopic ossification. Both of these
      patients also had evidence of right ventricular dilatation likely secondary to
      thoracic insufficiency. The third patient died from complications of a traumatic
      head injury after a fall but also had post-mortem evidence of thoracic
      insufficiency syndrome. All three patients had extensive, widespread heterotopic
      ossification and joint deformities consistent with FOP. There was extensive
      ossification of the spinal ligament in these patients, which may contribute to
      cervical spine rigidity. One patient was diagnosed post-mortem with a brainstem
      malformation. No additional significant abnormalities were noted in the other
      organ systems. Finally, we also demonstrate that cadaveric skin fibroblasts can
      be isolated for use as a potential source for future in vitro cell culture
      studies. CONCLUSIONS: This autopsy case series provides valuable information
      about the underlying complications of FOP and contributes significantly to our
      knowledge of this rare yet debilitating disorder. Thoracic insufficiency
      syndrome, right heart dysfunction, widespread heterotopic ossification, spinal
      ligament ossification, and CNS malformations were clearly evident; however, most
      other non-bone tissues appeared to be spared from gross malformations. Finally,
      the ability to isolate live cells from cadaveric skin is an important technique
      that will facilitate future studies, particularly as induced pluripotent stem
      cells and other cell-based technologies evolve. This case series highlights the
      importance of post-mortem examinations and their contribution to our current
      knowledge of disease pathophysiology and comorbidities.

PMID- 29033384
TI  - Transcatheter mitral valve replacement: looking beyond the implant.

PMID- 29033385
TI  - PCR Peripheral @ GISE: a unique educational link between peripheral endovascular
      solutions and interventional cardiologists.

PMID- 29033387
TI  - Survival and cause of death after transcatheter aortic valve replacement as
      compared to an age- and sex-matched background population.
AB  - AIMS: This study aimed to assess survival and causes of death in a real-world
      TAVR population as compared to an age- and sex-matched background population.
      METHODS AND RESULTS: Each aortic stenosis (AS) patient treated with TAVR in
      Eastern Denmark between 2007 and 2014 (n=617) was matched with 25 age- and sex
      matched controls (n=15,425) randomly drawn from the general Danish population. In
      the total TAVR population, early mortality (<=90 days) was significantly higher
      (hazard ratio [HR] 3.90 [2.82-5.39]; p<0.001) as compared to its background
      population, driven mainly by cardiovascular (CV) mortality. Late mortality (>90
      days) was not different between the TAVR and background population (HR 1.16 [0.96
      1.40]; p=0.126), causes of death being mainly non-CV. In subgroup analysis, the
      HR for late mortality was 0.98, 1.11, and 1.90 for the low-, intermediate-, and
      high-risk TAVR groups, respectively, as compared to their matched controls and
      1.04, 1.45, and 1.52 for the high gradient, paradoxical low-flow low-gradient (P
      LFLG), and classical LFLG (C-LFLG) groups, respectively, as compared to their
      controls. CONCLUSIONS: In general, AS patients who survive the first three months
      after TAVR have a similar survival to their matched controls. Relative survival
      benefit is the highest in low-to-intermediate risk AS patients with a high
      transvalvular gradient.

PMID- 29033386
TI  - "Breaking the code" of small bioprosthetic surgical valves.

PMID- 29033388
TI  - How should I treat an iatrogenic type IIA DeBakey-Stanford aortic dissection
      during a percutaneous right coronary artery intervention?

PMID- 29033383
TI  - Long-Term Exposure to Ambient Air Pollution and Incidence of Postmenopausal
      Breast Cancer in 15 European Cohorts within the ESCAPE Project.
AB  - BACKGROUND: Epidemiological evidence on the association between ambient air
      pollution and breast cancer risk is inconsistent. OBJECTIVE: We examined the
      association between long-term exposure to ambient air pollution and incidence of
      postmenopausal breast cancer in European women. METHODS: In 15 cohorts from nine
      European countries, individual estimates of air pollution levels at the residence
      were estimated by standardized land-use regression models developed within the
      European Study of Cohorts for Air Pollution Effects (ESCAPE) and Transport
      related Air Pollution and Health impacts - Integrated Methodologies for Assessing
      Particulate Matter (TRANSPHORM) projects: particulate matter (PM) <=2.5MUm,
      <=10MUm, and 2.5-10MUm in diameter (PM2.5, PM10, and PMcoarse, respectively);
      PM2.5 absorbance; nitrogen oxides (NO2 and NOx); traffic intensity; and elemental
      composition of PM. We estimated cohort-specific associations between breast
      cancer and air pollutants using Cox regression models, adjusting for major
      lifestyle risk factors, and pooled cohort-specific estimates using random-effects
      meta-analyses. RESULTS: Of 74,750 postmenopausal women included in the study,
      3,612 developed breast cancer during 991,353 person-years of follow-up. We found
      positive and statistically insignificant associations between breast cancer and
      PM2.5 {hazard ratio (HR)=1.08 [95% confidence interval (CI): 0.77, 1.51] per 5
      MUg/m3}, PM10 [1.07 (95% CI: 0.89, 1.30) per 10 MUg/m3], PMcoarse[1.20 (95% CI:
      0.96, 1.49 per 5 MUg/m3], and NO2 [1.02 (95% CI: 0.98, 1.07 per 10 MUg/m3], and a
      statistically significant association with NOx [1.04 (95% CI: 1.00, 1.08) per 20
      MUg/m3, p=0.04]. CONCLUSIONS: We found suggestive evidence of an association
      between ambient air pollution and incidence of postmenopausal breast cancer in
      European women. https://doi.org/10.1289/EHP1742.

PMID- 29033389
TI  - Chemical renal denervation: an effective method to treat resistant hypertension?

PMID- 29033390
TI  - Chemical sympathetic denervation: promising, but important distinctions between
      agents and methods.

PMID- 29033391
TI  - Breast diseases in children: the spectrum of radiologic findings in a cohort
      study.
AB  - PURPOSE: We aimed to investigate the spectrum of radiologic findings and referral
      reasons for breast diseases in children considering age-appropriate presentation.
      METHODS: Our retrospective cohort study included 348 consecutive pediatric
      patients aged <19 years (median, 13 years) referred to radiology with a clinical
      presentation between 2005 and 2016. Radiologic findings were reviewed in four age
      ranges (0-2 years, 2-8 years, 8-15 years, >15 years). RESULTS: Of 348 patients,
      257 had a referral reason. The most frequent referral reason was a palpable mass
      (35%). Developmental abnormalities accounted for 48% of all radiologic findings
      in 348 patients. We did not detect any breast malignancy. According to age
      groups, the most common radiologic findings were neonatal hypertrophy (0-2
      years), early breast development (2-8 years), developmental abnormalities by a
      majority of gynecomastia (8-15 years), and normal findings or developmental
      abnormalities (>15 years). Interestingly, the frequency of gynecomastia was only
      4% in neonatal period or early childhood. Fibroadenomas and fibroadenoma-like
      solid masses were seen after 8 years and constituted the majority of solid masses
      (65%). Cysts were seen at a rate of 7% and majority of them were of simple type,
      which tends to resolve in time. CONCLUSION: In our study, the most common
      referral reason to radiology was a palpable breast mass. Neonatal hypertrophy and
      early breast development in younger children, and developmental abnormalities in
      older children may be kept in mind as the most common radiologic findings. Our
      study confirms the substantial absence of malignancies in children as well as a
      widely different disease spectrum in comparison with the adult population.

PMID- 29033393
TI  - New bioactive glass scaffolds with exceptional qualities for bone tissue
      regeneration: response of osteoblasts and osteoclasts.
AB  - Tissue regeneration is a significantly improved alternative to tissue replacement
      by implants. It requires porous bioscaffolds for the restoration of natural
      tissue rather than relying on bio-inactive, often metallic implants. Recently, we
      developed technology for fabricating novel, nano-macroporous bioactive 'tailored
      amorphous multi-porous (TAMP)' hard tissue scaffolds using a 70 mol% SiO2-30 mol%
      CaO model composition. The TAMP silicate scaffolds, fabricated by a modified sol
      gel process, have shown excellent biocompatibility via the rapid formation of
      hydroxyapatite in biological fluids as well as in early tests with bone forming
      cells. Here we report an in depth investigation of the response of MC3T3-E1 pre
      osteoblast cells and bone marrow derived (BMD) osteoclasts to these TAMP
      scaffolds. Light and electron microscopic imaging, gene and protein expression,
      and enzyme activity analyses demonstrate that MC3T3-E1 pre-osteoblasts adhere,
      proliferate, colonize, and differentiate on and inside the bioactive TAMP
      scaffolds. Additionally, BMD precursor cells mature into active osteoclasts and
      remodel the scaffold, highlighting the exceptional qualities of this novel
      scaffold material for bone tissue regeneration.

PMID- 29033392
TI  - Mechanical recanalization in ischemic anterior circulation stroke within an 8
      hour time window: a real-world experience.
AB  - PURPOSE: We aimed to assess the safety and effectiveness of mechanical
      recanalization in patients with ischemic stroke in the anterior circulation
      within 8 h since symptoms onset and with unknown onset time. We compared time
      intervals <6 h vs. 6-8 h/unknown onset time, as only limited data are available
      for a time window beyond 6 h. METHODS: Our cohort included 110 consecutive
      patients (44 males; mean age, 73.0+/-11.5 years) with ischemic stroke in the
      anterior circulation due to the acute occlusion of a large intracranial artery
      who underwent mechanical recanalization within an 8-hour time window or with
      unknown onset time. All patients underwent unenhanced computed tomography (CT) of
      the brain, CT angiography of the cervical and intracranial arteries and digital
      subtraction angiography. Perfusion CT was performed in patients beyond a 6-hour
      time window/with unknown onset time. We collected the following data: baseline
      characteristics, presence of risk factors, neurologic deficit at the time of
      treatment, time to therapy, recanalization rate, and 3-month clinical outcome.
      Successful recanalization was defined as Thrombolysis in Cerebral Infarction
      score of 2b/3 and good clinical outcome as modified Rankin scale value of 0-2
      points. RESULTS: Successful recanalization was achieved in 82 patients (74.5%):
      in 61 patients treated within 6 h (73.5%), 7 patients treated within 6-8 h
      (63.6%), and 13 patients with unknown onset time (81.3%). Good 3-month clinical
      outcome was achieved in 61 patients (55.5%): in 46 patients treated within 6 h
      (55.4%), 5 patients treated within 6-8 h (45.5%), and 10 patients with unknown
      onset time (62.5%). Recanalization success or clinical outcome were not
      significantly different between patients treated at different time windows.
      CONCLUSION: Our data confirms the safety and effectiveness of mechanical
      recanalization performed in carefully selected patients with ischemic stroke in
      the anterior circulation within 8 h of stroke onset or with unknown onset time in
      everyday practice.

PMID- 29033394
TI  - Diagnostic biomarkers for lung cancer prevention.
AB  - Lung cancer is the leading cause of death for neoplasm. Lung cancer mortality is
      frequently associated with late diagnosis, therefore an early diagnosis is a key
      factor to significantly improve overall survival in high risk populations of
      asymptomatic patients. Conventional cancer screenings (low-dose computed
      tomography or chest x-ray) today offer early detection but are invasive and
      expensive. Previously these studies evaluated the solid and topographic cancer
      structure and morphology. Today the concept of tumor has been remodelled, being
      defined as a disease that has its own genetic, biological and metabolic identity;
      it is on this new awareness that we should base new screening methods. Recent
      research has shown great reliability of new tests such as exhaled breath
      analysis, serum biomarkers and urine analysis in early diagnosis of lung cancer.
      Analysis of new biomarkers associated with the high specificity of these new
      screening methods, which are non-invasive, safe, inexpensive and simple to
      perform, could allow a non-invasive approach to determine a big change in the
      early diagnosis of cancer and its survival rate. Furthermore, these new
      techniques put the patient at the core of a non-invasive diagnostic process and
      ensure a better quality of life during medical diagnosis. In this article, we
      want to analyze the possible benefits of these new and promising methods,
      suggesting a possible combination between them to ensure, as soon as possible, an
      early and effective diagnosis of lung cancer with a special focus on the patient,
      in a new era of personalized medicine.

PMID- 29033396
TI  - Depression in Cancer Care.
AB  - Depression is common among cancer patients and their families, and may lead to
      substantial clinical consequences. Clinicians should routinely screen cancer
      patients for comorbid depression and should provide appropriate care at both
      primary and specialized care levels. Good quality care is beneficial not only for
      cancer patients themselves but also for their family members. It includes good
      communication between patients and health providers, and addressing of unmet
      needs of cancer patients. Specialized care comprises pharmacotherapy and
      psychotherapy. The advancement of psychotherapy for cancer patients parallels the
      advancement of general psychotherapy. Among the many types of psychotherapies,
      mindfulness-based interventions have been attracting growing attention. Some
      relevant studies that have been conducted in Keio University Hospital are
      described herein.

PMID- 29033395
TI  - Perioperative changes in exhaled nitric oxide during oesophagectomy.
AB  - INTRODUCTION: Oesophagectomy is a major surgical procedure, associated with high
      rates of postoperative cardiopulmonary morbidity, that is in part due to the
      frequent requirement for periods of intraoperative one-lung ventilation (OLV).
      The current pilot study aims to investigate variation in exhaled NO levels during
      oesophagectomy with emphasis on the response to OLV and correlation to
      physiological variables and clinical outcomes. METHODS: Breath-to-breath
      concentrations of NO were analysed in patients undergoing oesophagectomy at
      various stages of two-lung ventilation. Furthermore, we also analysed the effects
      of OLV both in the selectively ventilated and collapsed lungs. RESULTS: Twenty
      four patients were recruited to the study (17 male, 60.2 +/- 12.8 years).
      Regarding two-lung ventilation, the baseline levels of NO (2.9 ppb), tended to
      increase after re-inflation of the collapsed lung (3.5 ppb, P = 0. 888) and
      decreased at 2 h (2.1 ppb, P = 0.022) and 12 h (2.2 ppb, P = 0.733)
      postoperatively. Compared to baseline, selective measurements of NO at the end of
      OLV demonstrated a significant reduction of NO levels in the ventilated lung (1.6
      versus 3.1 ppb, P = 0.028), whereas re-inflation of the collapsed lung revealed
      higher levels of NO (3.4 versus 2.7 ppb, P = 0.657). Exhaled NO correlated
      significantly with systolic blood pressure and lactate (P < 0.007). Exhaled NO
      levels tended to be higher at all perioperative time points in patients who
      developed postoperative respiratory complications (P > 0.05). CONCLUSION: This
      study highlights effects of oesophagectomy and OLV on exhaled concentrations of
      NO. The observed variations may be related to differential ventilation during OLV
      altering the complex balance between synthesis and consumption of NO as well as
      local and generalised tissue injury associated with this surgery. Findings should
      prompt further larger studies to establish the relationship between exhaled NO
      and lung injury both during and after oesophagectomy and one-lung ventilation.

PMID- 29033397
TI  - A transvaginal endoscopy-based technique for performing ovarian examinations in
      sows.
AB  - For examining pig ovaries, which have complex structures, laparoscopy is a useful
      technique, but requires general anesthesia; therefore, it cannot be performed
      repeatedly within a short period of time. We report a transvaginal endoscopy
      based technique for conducting ovarian examinations without general anesthesia.
      Sows were sedated in pig stalls. Using a colonoscope, the vaginal wall was
      punctured with a trocar. To avoid the trocar being caught in the broad ligament
      of the uterus or the connective tissue around the vagina, the trocar was inserted
      close to the external uterine os and between the 2:00 and 3:00 or the 9:00 and
      10:00 positions (in a clockwise direction). Then, a urethroscope was inserted
      into the abdomen, and an examination was carried out after the ovaries had been
      moved towards the urethroscope camera via rectal palpation. This less invasive
      procedure may allow repeated examinations and will increase our understanding of
      ovarian dynamics in pigs.

PMID- 29033398
TI  - Intensive Education of Health Care Workers Improves the Outcome of Ebola Virus
      Disease: Lessons Learned from the 2014 Outbreak in Sierra Leone.
AB  - The rare and deadly Ebola virus disease (EVD) is caused by Ebola virus (EBOV)
      infection. The 2014-2015 EVD outbreak in West Africa was unprecedented. Person-to
      person transmission of EBOV by direct contact with the body or bodily fluids of
      an infected person through broken skin or unprotected mucous membrane caused
      rapid outbreak in communities. Nosocomial infection was the cause of death of
      many health care workers (HCWs). This paper aims to reveal the importance and
      effect of intensive education of HCWs when combating an outbreak such as EVD. We
      compared the curricula of two educational programs and analyzed their effects by
      the trend of weekly new patients. In September 2014, a three-day training program
      on infection, prevention and control (IPC) was organized for nurses, but it was
      not sufficient to achieve good outcome. In December 2014, a newly established
      National Ebola Training Academy was set up to offer a platform of clinical
      training modules for frontline Ebola response workers. This academy addressed the
      training needs of clinicians and hygienists who were working or will work at
      Ebola treatment centers that were established after the onset of the 2014
      outbreak. Increased intensive contents and simulated training at the academy
      improved HCWs' understanding of EVD, IPC and patient care, which subsequently
      contributed to the survival of patients. The rapid settlement of the outbreak
      after introducing the Academy indicates that appropriate intensive education of
      HCWs is the key activity carried out to control the outbreak of EVD in Sierra
      Leone.

PMID- 29033400
TI  - Protective effects of luteolin-7-O-glucoside against starvation-induced injury
      through upregulation of autophagy in H9c2 Cells.
AB  - Cardiomyocyte nutrient deprivation is a common clinical event that mediates
      various cardiac ischemic processes and is associated with autophagy activation
      and cell survival or death. Luteolin-7-O-glucoside (LUTG) was one of the
      flavonoid glycosides isolated from Dracocephalum tanguticum. Previous research
      had showed that LUTG pretreatment had significant protective effects against
      doxorubicin-induced cardiotoxicity. However, whether LUTG could protect
      cardiomyocytes from starvation-induced injury was not clear. In this study,
      cardioprotection and mechanisms of LUTG against starvation-induced injury were
      investigated in vitro. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-tetrazolium
      bromide (MTT) assay showed starvation-induced autophagy is a homeostatic and
      protective response for H9c2 cell survival. LUTG could protect against injury
      induced by starvation in H9c2 cells. Acridine orange (AO) staining showed that
      pretreatment with LUTG enhanced lysosomal autophagy. Western blotting indicated
      that LUTG enhanced autophagy by down-regulating the expression of phospho
      extracellular signal regulated kinase1/2 (p-ERK), phospho-protein kinase B (p
      Akt) and phospho-mammalian target of rapamycin (p-mTOR). These results suggest
      that LUTG might act as a promising therapeutic agent for preventing starvation
      induced cardiotoxicity by upregulation of autophagy through the Akt/mTOR and ERK
      signal pathway.

PMID- 29033399
TI  - The contribution of efficient production of monozygotic twins to beef cattle
      breeding.
AB  - Production of sires with high breeding potential is indispensable for prompt and
      reliable breeding using their semen in the cattle industry. Currently, in Japan,
      we aim to further the production of Japanese black sires via a new breeding
      system that uses genetically homologous monozygotic twins so that better growth
      performance and carcass traits can be translated to the increased production of
      beef with higher economic value. Several studies have reported that monozygotic
      twins are produced by embryo bisection. On the other hand, with the evolution and
      stabilization of in vitro fertilization technology, it has become possible to
      produce multiple monozygotic twin calves from blastomeres separated from a
      cleavage-stage embryo. This review attempts to clarify breeding practices through
      revalidation of the factors that affect the production efficiency of monozygotic
      twin calves by embryo bisection. Furthermore, the establishment of a system for
      monozygotic twin embryo production via the simplified technique of blastomere
      separation is reviewed while showing data from our previously performed studies.

PMID- 29033401
TI  - Construction of C35 gene bait recombinants and T47D cell cDNA library.
AB  - C35 is a novel tumor biomarker associated with metastasis progression. To
      investigate the interaction factors of C35 in its high expressed breast cancer
      cell lines, we constructed bait recombinant plasmids of C35 gene and T47D cell
      cDNA library for yeast two-hybrid screening. Full length C35 sequences were
      subcloned using RT-PCR from cDNA template extracted from T47D cells. Based on
      functional domain analysis, the full-length C351-348bp was also truncated into
      two fragments C351-153bp and C35154-348bp to avoid auto-activation. The three
      kinds of C35 genes were successfully amplified and inserted into pGBKT7 to
      construct bait recombinant plasmids pGBKT7-C351-348bp, pGBKT7-C351-153bp and
      pGBKT7-C35154-348bp, then transformed into Y187 yeast cells by the lithium
      acetate method. Auto-activation and toxicity of C35 baits were detected using
      nutritional deficient medium and X-alpha-Gal assays. The T47D cell ds cDNA was
      generated by SMARTTM technology and the library was constructed using in vivo
      recombination-mediated cloning in the AH109 yeast strain using a pGADT7-Rec
      plasmid. The transformed Y187/pGBKT7-C351-348bp line was intensively inhibited
      while the truncated Y187/pGBKT7-C35 lines had no auto-activation and toxicity in
      yeast cells. The titer of established cDNA library was 2 * 107 pfu/mL with high
      transformation efficiency of 1.4 * 106, and the insert size of ds cDNA was
      distributed homogeneously between 0.5-2.0 kb. Our research generated a T47D cell
      cDNA library with high titer, and the constructed two C35 "baits" contained a
      respective functional immunoreceptor tyrosine based activation motif (ITAM) and
      the conserved last four amino acids Cys-Ile-Leu-Val (CILV) motif, and therefore
      laid a foundation for screening the C35 interaction factors in a BC cell line.

PMID- 29033402
TI  - 5-aminolevulinic acid (5-ALA) fluorescence-guided Mohs surgery resection of
      penile-scrotal extramammary Paget's disease.
AB  - This report aims to evaluate the usefulness of 5-aminolevulinic acid (5-ALA)
      fluorescence-guided Mohs surgery resection of penile-scrotal extramammary Paget's
      disease for achieving maximum tumor resection. Between January 2014 and December
      2015, 5 patients underwent surgical resection of a penile-scrotal extramammary
      Paget's disease in department of urology, Huashan hospital, Fudan University. All
      patients were coated with 5-ALA (concentration of 20%) throughout the scrotum and
      the visible range of the lesion plus a 2cm margin 3 hours before the induction of
      anesthesia. 5-ALA fluorescence was visualized using an ultraviolet (UV) light at
      405 nm. Surgical margin was determined in a standardized manner. The extent of
      resection was evaluated on the basis of frozen and histology sections. If the
      fluorescence positive punctate lesions were found outside the resection range, we
      removed the lesions and sent them for pathological examination. All data were
      prospectively collected, and the short- and long-term outcomes of the treatment
      strategy were analyzed. Lesions in the blue light turns red after irradiation,
      the fluorescence-guided surgery delineated range is less than the naked eye,
      intraoperative frozen prompted negative margins, postoperative pathological
      diagnosis. A total of 31 scattered lesions were found. After biopsy pathology
      prompted four were positive. In conclusion, 5-ALA fluorescence-guided minimum
      range can be completely removed in penile-scrotal Paget's lesions, and it is able
      to detect distant scattered lesions.

PMID- 29033403
TI  - Development of a new test cell to measure cumulative permeation of water
      insoluble pesticides with low vapor pressure through protective clothing and
      glove materials.
AB  - A collaborative approach, involving resources and expertise from several
      countries, was used to develop a test cell to measure cumulative permeation by a
      solid-state collection technique. The new technique was developed to measure the
      permeation of pesticide active ingredients and other chemicals with low vapor
      pressure that would otherwise be difficult to test via standard techniques. The
      development process is described and the results from the final chosen test
      method are reported. Inter-laboratory studies were conducted to further refine
      the new method and determine repeatability and reliability. The revised test
      method has been approved as a new ISO/EN standard to measure permeation of
      chemicals with low vapor pressure and/or solubility in water.

PMID- 29033404
TI  - Prediction of WBGT-based clothing adjustment values from evaporative resistance.
AB  - Wet bulb globe temperature (WBGT) index is used by many professionals in
      combination with metabolic rate and clothing adjustments to assess whether a heat
      stress exposure is sustainable. The progressive heat stress protocol is a
      systematic method to prescribe a clothing adjustment value (CAV) from human wear
      trials, and it also provides an estimate of apparent total evaporative resistance
      (Re,T,a). It is clear that there is a direct relationship between the two
      descriptors of clothing thermal effects with diminishing increases in CAV at high
      Re,T,a. There were data to suggest an interaction of CAV and Re,T,a with relative
      humidity at high evaporative resistance. Because human trials are expensive,
      manikin data can reduce the cost by considering the static total evaporative
      resistance (Re,T,s). In fact, as the static evaporative resistance increases, the
      CAV increases in a similar fashion as Re,T,a. While the results look promising
      that Re,T,s can predict CAV, some validation remains, especially for high
      evaporative resistance. The data only supports air velocities near 0.5 m/s.

PMID- 29033405
TI  - Construction and expression of vectors encoding biologically active rodent
      gonadotropins.
AB  - The gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone
      (FSH), are important hormones in vertebrate reproduction. The isolation of
      gonadotropins from the pituitary gland is sub-optimal, as the cross-contamination
      of one hormone with another is common and often results in the variation in the
      measured activity of LH and FSH. The production of recombinant hormones is,
      therefore, a viable approach to solve this problem. This study aimed to express
      recombinant rat, mouse, and mastomys FSH and LH in Chinese hamster ovary (CHO)
      cells. Their common alpha-subunits along with their hormone-specific beta
      subunits were encoded in a single mammalian expression vector. FSH from all three
      species was expressed, whereas expression was achieved only for the mouse LH.
      Immunohistochemistry for rat alpha subunit of glycoprotein hormone (alphaGSU) and
      LHbeta and FSHbeta subunits confirmed the production of the dimeric hormone in
      CHO cells. The recombinant rodent gonadotropins were confirmed to be biologically
      active; estradiol production was increased by recombinant FSH in granulosa cells,
      while recombinant LH increased testosterone production in Leydig cells.

PMID- 29033406
TI  - Different Behavior of Bioresorbable Vascular Scaffold and Metallic Stent With
      Positive Vessel Remodeling.

PMID- 29033407
TI  - First Report of Swim Bladder-Associated Microbiota in Rainbow Trout (Oncorhynchus
      mykiss).
AB  - The aim of the present study was to identify major bacteria associated with the
      swim bladder in the rainbow trout, Oncorhynchus mykiss. We extracted DNA from the
      swim bladder and gut contents in order to perform a temporal temperature gradient
      gel electrophoresis (TTGE) analysis of 16S rRNA amplicons for bacterial
      identification to further compare both profiles. Arthrobacter and
      Cellulosimicrobium were the major genera observed in the swim bladder in fish,
      but were not present in fish gut contents; Mycoplasma were instead observed in
      these samples. Further research to investigate the possible symbiotic roles of
      the swim bladder-associated microbiota in salmonids is needed.

PMID- 29033408
TI  - Transrectal guidance of the ovaries reduces operative time during bovine
      laparoscopic ovariectomy.
AB  - The main objective of this study was to evaluate the effects of transrectal
      guidance of the ovaries by an assistant on operative time during bovine
      laparoscopic ovariectomy. Twenty four clinically healthy Holstein dairy cows were
      divided randomly into two groups. In the transrectal guidance group, an assistant
      grasped the ovaries via the transrectal route and pulled them to a position where
      they could be visualized with a camera. On the other hand, the control group was
      operated without guidance. The time required to remove both ovaries in the
      guidance group was shorter than that in the control group (P<0.01). We concluded
      that laparoscopic ovariectomy with transrectal guidance of the ovaries can
      substantially shorten operative time, thereby greatly contributing to animal
      welfare and to reducing the burden on the operator.

PMID- 29033409
TI  - Evaluation of serum ferritin and thyroid function in the second trimester of
      pregnancy.
AB  - Ferritin is a universal intracellular protein that acts as an iron carrier.
      Several studies have indicated that iron deficiency affects thyroid function in
      non-pregnant women. Our objective was to assess the relationship between serum
      ferritin levels and thyroid function in pregnant women during the second
      trimester. Pregnant women with sufficient iodine intake and normal antithyroid
      antibodies during the second trimester were recruited from the obstetric
      outpatient department of the Fifth People's Hospital of Fudan University. Serum
      ferritin (SF) levels, thyroid function, anti-thyroid antibodies and vitamin B12
      were determined by electrochemiluminescence immunoassay kit. Maternal serum iron
      (Fe), unsaturated iron binding capacity (UIBC), hemoglobin (Hb), creatinine (Cr),
      fasting blood glucose (FBG), and alanine aminotransferase (ALT) were also
      evaluated. Stepwise regressions performed to evaluate the associations between SF
      and other maternal parameters. In the second trimester, 11.4% pregnant women had
      a SF concentration less than 12 MUg/L, and 7.6% pregnant women were anemic. SF
      levels were negatively correlated with serum TSH levels (r = -0.219, p < 0.05),
      and positively correlated with FT4 levels (r = 0.203, p < 0.05). Linear
      regression analysis showed only SF, age, week of gestation were significant
      predictors of regression with TSH as the dependent variable (beta: -0.007, 
      0.059, and 0.118 respectively; all p < 0.05). However consistent relation between
      the SF levels and FT4 was not observed in stepwise linear regression. Maternal
      iron status is a determinant of TSH concentrations during pregnancy in pregnant
      women during the second trimester.

PMID- 29033410
TI  - Total Small Vessel Disease Score in Neurologically Healthy Japanese Adults in the
      Kashima Scan Study.
AB  - Objective We explored the association between the total small vessel disease
      (SVD) score obtained with magnetic resonance imaging and risk factors and
      outcomes in the Japanese population. Methods The presence of SVD features,
      including lacunes, cerebral microbleeds, white matter changes, and basal ganglia
      perivascular spaces on MRI, was summed to obtain a "total SVD score" (range 0-4).
      Ordinal and multinomial logistic regression analyses were performed to
      investigate the association of higher total SVD scores with vascular risk
      factors, the Mini-Mental State Examination (MMSE) score, and cerebral atrophy.
      Results We included 1,451 neurologically healthy adults (mean age, 57.1 years;
      47% male). A multivariate ordinal logistic regression analysis showed that the
      total SVD score was associated with aging, hypertension, blood pressure (BP),
      diabetes mellitus, MMSE score, and deep cerebral atrophy, but the equal slopes
      assumption between scores did not hold. A multivariate multinomial logistic
      regression analysis (total SVD score 0=reference) showed that aging,
      hypertension, and BP were positively associated with scores of 1, 2, or >=3.
      These effects, presented as odds ratios (ORs), increased as the score increased
      and were strongest with a score of >=3 [aging (per 10-year increment), OR 4.00,
      95% confidence interval (CI) 2.47-6.46; hypertension, OR 5.68, 95% CI 2.52-12.80;
      systolic BP (per standard deviation increase), OR 1.96, 95% CI 1.41-2.74,
      respectively]. Diabetes mellitus and deep cerebral atrophy tended to be
      associated with the SVD scores. The MMSE score showed no consistent associations.
      Conclusion The total SVD score may be a promising tool for indexing SVD, even in
      the Japanese population.

PMID- 29033411
TI  - Relationship between the Clinical Course of Ulcerative Colitis during Pregnancy
      and the Outcomes of Pregnancy: A Retrospective Evaluation.
AB  - Objective Little information is available on the relationship between the
      clinical course of ulcerative colitis (UC) and the outcomes of pregnancy and
      delivery in pregnant Japanese women. The aim of this retrospective study was to
      determine the factors that influence pregnancy and childbirth in middle-aged UC
      patients. Methods We studied 53 pregnancies in 45 pregnant women with UC who
      delivered at our department. They included 41 pregnancies that started while in
      UC remission and 12 pregnancies that started in the UC active phase. The
      following factors were evaluated: 1) the clinical course of UC; 2) the frequency
      and details of abnormal pregnancy/abnormal delivery; and 3) the course of
      pregnancy/delivery. We compared the clinical features, course of UC, and details
      of treatment between women with a normal pregnancy/delivery and those with an
      abnormal delivery. Results A comparison of the remission and acute groups showed
      lower clinical activity indices (CAIs) during pregnancy in the remission group
      and significantly higher rates of recurrence/exacerbation in the active group
      (75%) than in the remission group (7.3%). The respective CAIs in the first,
      second, and third trimesters were 3 and 6, 3 and 5, and 3 and 4, in the remission
      and active groups, respectively. Live infants were delivered in 51 (96%)
      pregnancies, with 7 (17%) abnormal pregnancies in the remission group and 4
      (33.3%) in the active group (p>0.05). Abnormal delivery occurred in 16 of 53
      (30.1%) pregnancies, and the rate was higher in the remission group than in the
      active group (p>0.05). In both groups, the most common abnormal event during
      pregnancy was delivery of low-birth-weight infants. Delivery was normal in 37
      cases and abnormal in 16 cases. A multivariate analysis showed that a shorter UC
      disease duration (odds ratio=1.16) and higher CAI in the first trimester (odds
      ratio=1.49) were associated with an increased risk of abnormal pregnancy.
      Conclusion Our findings demonstrated that the clinical course of UC, as evaluated
      by the CAI, during pregnancy influenced the outcome of pregnancy and delivery.

PMID- 29033413
TI  - Multiple Lung Cysts Due to pneumocystis jirovecii Pneumonia.

PMID- 29033412
TI  - Emergency Caesarean Section Saved Both an Anti-MuSK Antibody-positive Myasthenia
      Gravis Mother with Pregnancy-induced Hypertension and Her Premature Baby.
AB  - We herein report the case of a 46-year-old pregnant woman with anti-muscle
      specific kinase (MuSK) antibody-positive myasthenia gravis (MG) who showed
      pregnancy-induced hypertension and developed respiratory failure at 30 weeks and
      5 days of pregnancy, and who underwent an emergency caesarean section (CS). Her
      MG symptoms gradually improved in the subsequent weeks. The premature baby with
      positive MuSK antibodies was successfully delivered, but the male baby required
      temporary artificial ventilation. However, his condition also gradually improved
      over time. The present case suggests that an emergency CS could rescue both the
      mother, who was in critical condition, and the prematurely born baby, even when
      suffering from acute respiratory insufficiency.

PMID- 29033414
TI  - Spontaneous Regression of Allergic Bronchopulmonary Mycosis Due to Curvularia
      lunata.
AB  - Allergic bronchopulmonary mycosis (ABPM) is a pulmonary hypersensitivity disease
      mainly caused by Aspergillus fumigatus. The mainstay treatment for ABPM is
      systemic corticosteroid therapy. A 25-year-old man presented with pulmonary
      infiltrates. His peripheral eosinophil, total serum IgE, and serum Aspergillus
      specific IgE levels were elevated. The patient tested positive in a skin test for
      Aspergillus. However, sputum cultures revealed a Curvularia lunata infection. We
      therefore diagnosed ABPM possibly caused by C. lunata, which is rare in Japan.
      The clinical state of the patient improved under observation. Identification of
      the causative fungus is an important aspect of the ABPM diagnosis.

PMID- 29033415
TI  - Liver Cyst Infection after Colon Endoscopic Mucosal Resection in a Patient with
      Autosomal Dominant Polycystic Kidney Disease on Maintenance Hemodialysis.
AB  - A 60-year-old Japanese man with autosomal dominant polycystic kidney disease
      (ADPKD) on maintenance hemodialysis underwent colonoscopy and endoscopic mucosal
      resection (EMR). He was hospitalized after 4 days of fever that began the day
      following colonoscopy. We detected Klebsiella pneumoniae in a blood culture and a
      ring-shaped integration in the liver cyst by gallium scintigraphy. He recovered
      with antibiotics and percutaneous drainage. The patient was believed to have
      contracted the liver cyst infection via an injured colonic mucosa and portal
      vein. Thus, if a patient exhibits fever after a colon EMR, for patients with
      ADPKD, then a liver cyst infection should also be considered in the differential
      diagnosis.

PMID- 29033417
TI  - Pseudohypoparathyroidism Causing Multiple Brain Calcifications.

PMID- 29033416
TI  - Progression of Hepatic Hypovascular Nodules with Hypointensity in the
      Hepatobiliary Phase of Gd-EOB-DTPA-enhanced MRI in Hepatocellular Carcinoma
      Cases.
AB  - Objective We investigated the possible factors for predicting the future
      progression to hepatocellular carcinoma (HCC) from hypovascular nodules detected
      in the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine
      pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI). Methods A
      total of 91 hypovascular nodules detected by Gd-EOB-DTPA-MRI in 28 patients
      without any past history of treatment for HCC were retrospectively examined. The
      nodules were categorized into those with and without HCC progression, then
      comparisons were made to identify any factors possibly related to a progression
      to HCC in each case. In addition, we performed a receiver operating
      characteristics (ROC) analysis to determine the cut-off value for the initial
      nodule size for predicting HCC progression within 12 months. Results The
      observation period of the 28 patients was 1,172.6+/-95.6 (mean+/-standard error)
      days. The number of hypovascular nodules that changed to hypervascular ones was
      15 (16.5%), and the cumulative incidence of hypervascular transformation was 7.1%
      at 12 months and 12.7% at 24 months. Of all 91 hypovascular nodules, 33 in 18
      patients were diagnosed as HCC based on hypervascular transformation and/or size
      enlargement, while the remaining 58 did not progress to HCC. There was no
      significant difference regarding the background characteristics between the HCC
      progressed and non-progressed groups according to a multivariate analysis, or
      between the patients who had nodules that progressed to HCC and those with
      nodules that did not progress to HCC. Regarding HCC progression at 12 months, the
      area under the ROC (AUROC) had a level of 0.745 and showed that an initial nodule
      cut-off size of 9.5 mm (sensitivity, 57.9%; specificity, 87.3%) was predictive.
      Conclusion In patients without a past HCC treatment history, it is difficult to
      determine whether hypovascular nodules have a high risk of progression to HCC
      based on background factors alone.

PMID- 29033418
TI  - Primary and Secondary Syphilis as Chancre of the Mouth with Rash.

PMID- 29033419
TI  - Successful Osimertinib Rechallenge with Steroid Therapy after Osimertinib-induced
      Interstitial Lung Disease.
AB  - A 62-year-old male with lung adenocarcinoma harboring an exon 19 deletion in the
      Epidermal growth factor receptor (EGFR) was treated with EGFR-tyrosine kinase
      inhibitors (TKIs) and several cytotoxic agents. After administering a fifth-line
      chemotherapy regimen, a liver biopsy revealed a diagnosis of recurrence with a
      T790M mutation. After an 82-day course of osimertinib therapy, the patient
      developed osimertinib-induced interstitial lung disease (ILD). Osimertinib was
      discontinued, and oral prednisolone was started. The ILD quickly improved, but
      liver metastases progressed and osimertinib was restarted concurrently with
      prednisolone. The patient showed neither disease progression nor a recurrence of
      ILD at 5 months. In situations in which no alternative treatment is available,
      osimertinib rechallenge should thus be considered as an alternative treatment.

PMID- 29033420
TI  - Usefulness of Bronchial Thermoplasty for Patients with a Deteriorating Lung
      Function.
AB  - Bronchial thermoplasty is a novel procedure for patients with severe asthma
      showing a stable lung function. We herein report two cases with a deteriorating
      lung function. The lung function tended to improve in one case, while the other
      case discontinued mepolizumab medication after the procedure. Treatment was
      performed safely under general anesthesia in both cases. The use of bronchial
      thermoplasty may therefore be useful for the treatment of patients with a
      deteriorating lung function.

PMID- 29033423
TI  - Recurrent Bleeding from a Hepatic Artery Pseudoaneurysm after Biliary Stent
      Placement.
AB  - A 78-year-old woman was admitted with benign biliary stenosis. A plastic stent
      was placed at the left branch to prevent obstructive cholangitis. Two weeks after
      the procedure, the patient was readmitted with cholangitis caused by hemobilia.
      However, computed tomography (CT), endoscopic retrograde cholangiopancreatography
      (ERCP), peroral cholangioscopy, and abdominal angiography failed to establish the
      bleeding source. At the seventh bleeding, CT revealed a hepatic artery
      pseudoaneurysm for which coil embolization was successfully performed. Hemobilia
      after plastic stent placement is extremely rare. We urge clinicians to consider
      the possibility of a pseudoaneurysm near the stent when trying to identify the
      bleeding source.

PMID- 29033421
TI  - The Resolution of Helicobacter suis-associated Gastric Lesions after Eradication
      Therapy.
AB  - A reddish depressed lesion was found in the corpus of the stomach of a 56-year
      old man. Gastric biopsy showed no findings of mucosa-associated lymphoid tissue
      lymphoma, including lympho-epithelial lesions. A urea breath test, stool antigen
      test and serum IgG antibody to Helicobacter pylori test were negative. Magnifying
      endoscopy using narrow-band-imaging showed no malignant structures. Gastric
      biopsy specimens were subjected to immunohistochemistry and a polymerase chain
      reaction, which identified Helicobacter suis infection. Triple therapy with
      esomeprazole, metronidazole, and amoxicillin was administered for 10 days. Three
      months later, endoscopy showed the significant improvement of the lesion. H. suis
      infection should be considered in chronic gastritis patients without H. pylori
      infection.

PMID- 29033422
TI  - Hepatic Pseudolymphoma with an Occult Hepatitis B Virus Infection.
AB  - A 49-year-old woman who was asymptomatic was found to have a small liver tumor on
      abdominal ultrasonography (US) at her annual health checkup. US revealed a
      hypoechoic, solid, mass measuring 17-mm in size in segment 6. The tumor markers
      associated with liver malignancy were negative. An infectious disease screen was
      negative for hepatitis B surface antigen, but positive for antibody to hepatitis
      B core antigen. Imaging studies using computed tomography (CT), magnetic
      resonance imaging (MRI), and CT angiography suggested a malignant liver tumor,
      such as hepatocellular carcinoma. Partial hepatic resection of the posterior
      segment was performed. The pathological diagnosis was pseudolymphoma of the
      liver.

PMID- 29033424
TI  - Diffuse Alveolar Hemorrhage in IgA Vasculitis with an Atypical Presentation.
AB  - IgA vasculitis (IgAV) commonly occurs in young children, who present with a
      tetrad of purpura, abdominal pain, arthralgia and nephritis. Diffuse alveolar
      hemorrhage (DAH) is a rare complication of IgAV. We herein report an adult case
      of IgAV with a presentation of DAH and nephritis (pulmonary renal syndrome, PRS),
      but without other typical manifestations, such as purpura, abdominal pain and
      arthralgia. A 33-year-old man presented with hemoptysis and a low-grade fever and
      was diagnosed to have IgAV based on the results of a renal biopsy. Treatment with
      corticosteroids, cyclophosphamide, and plasmapheresis was effective. IgAV should
      therefore be considered in the differential diagnosis of adult PRS.

PMID- 29033425
TI  - Evaluation by MR Enterocolonography of Lansoprazole-induced Collagenous Colitis
      Accompanied with Protein-losing Enteropathy.
AB  - We herein describe a 69-year-old man suffering from chronic diarrhea caused by
      lansoprazole (LPZ)-induced collagenous colitis (CC) accompanied with protein
      losing enteropathy (PLE), diagnosed by increased fecal alpha-1 antitrypsin
      clearance and the findings of leakage from the descending colon to the sigmoid
      colon on scintigraphy. MR enterocolonography (MREC) was also performed for
      differentiating digestive diseases, and inflamed findings were observed around
      the same portion as those on scintigraphy, suggesting that this region was
      responsible for protein loss in this case. The MREC findings improved after the
      cessation of LPZ, and hypoalbuminemia also improved simultaneously. This case
      suggests that MREC may be a new and useful diagnostic tool for CC with PLE.

PMID- 29033426
TI  - Fracture of a Colonic Self-expandable Metallic Stent in Malignant Colonic
      Obstruction.
AB  - Self-expandable metallic stents (SEMSs) are used for the management of malignant
      colorectal obstruction. A patient who underwent colonic uncovered SEMS insertion
      for extraluminal stenosis in the splenic flexure of the transverse colon due to
      advanced gastric cancer is herein reported. The patient presented with a fracture
      of the colonic SEMS 494 days after SEMS insertion. Although various complications
      of stenting have previously been reported, the details of fractures of colonic
      SEMSs have not yet been reported. Because the improvement in the prognosis for
      patients who undergo palliative SEMS insertion leads to long-term SEMS placement,
      diverse complications can thus be expected, and new events like stent fracture
      are expected to increase in the future.

PMID- 29033428
TI  - The Efficacy of Reduced-dose Dasatinib as a Subsequent Therapy in Patients with
      Chronic Myeloid Leukemia in the Chronic Phase: The LD-CML Study of the Kanto CML
      Study Group.
AB  - Objective The aim of this study was to prospectively investigate the efficacy and
      safety profiles of low-dose dasatinib therapy (50 mg once daily). Methods
      Patients with chronic myeloid leukemia in the chronic phase (CML-CP) who were
      being treated with low-dose imatinib (<=200 mg/day), but were resistant to this
      agent were enrolled in the current study (referred to as the LD-CML study).
      Results There subjects included 9 patients (4 men and 5 women); all were treated
      with dasatinib at a dose of 50 mg once daily. Among 8 patients who had not
      experienced major molecular response (MMR; BCR-ABL1 transcript <=0.1% according
      to International Scale [IS]) at study enrollment, 5 attained MMR by 12 months. In
      particular, 3 of 9 patients demonstrated a deep molecular response (DMR; IS
      <=0.0069%) by 18 months. Five patients developed lymphocytosis accompanied by
      cytotoxic lymphocyte predominance. There was no mortality or disease progression,
      and all continue to receive dasatinib therapy at 18 months with only 2 patients
      requiring dose reduction. Toxicities were mild-to-moderate, and pleural effusion
      was observed in 1 patient (grade 1). Conclusion Low-dose dasatinib can attain MMR
      and DMR without severe toxicity in patients with CML-CP who are unable to achieve
      MMR with low-dose imatinib. Switching to low-dose dasatinib should therefore be
      considered for patients in this setting, especially if they are otherwise
      considering a cessation of treatment.

PMID- 29033427
TI  - IgG4-related Lung Pseudotumor and Pleural Inflammation with Autoimmune Hepatitis.
AB  - A 63-year-old man was admitted to our department following a secondary medical
      examination. Blood tests showed high levels of liver enzymes, IgG, IgG4, and
      antinuclear antibody. Computed tomography showed tumors in the bilateral lower
      lobes of the lungs and pleural thickening. After pleural and liver biopsy
      procedures, he was conclusively diagnosed with IgG4-related lung pseudotumor and
      pleural inflammation with autoimmune hepatitis. We started treatment with
      prednisolone 40 mg/day, and chest radiograph and blood tests showed signs of
      improvement. This was a rare case that suggested an association between IgG4
      related disease and autoimmune hepatitis.

PMID- 29033429
TI  - Cowden Syndrome with a Novel PTEN Mutation Presenting with Partial Epilepsy
      Related to Focal Cortical Dysplasia.
AB  - Cowden syndrome is a rare autosomal dominant disorder characterized by multiple
      hamartomas of the ectoderm and brain. A 36-year-old Japanese man presented with
      right facial seizure during sleep and was admitted to our hospital. He showed
      cobblestoning over the tongue and palmar pitting but no neurological
      abnormalities while he was not having a seizure. Brain magnetic resonance imaging
      showed focal cortical dysplasia in the left frontal lobe. Electroencephalography
      showed sharp waves over the left frontal lesion. A genetic analysis revealed a
      novel mutation of PTEN. The administration of carbamazepine ended the seizures.
      This is the first Japanese case of Cowden syndrome with a novel PTEN gene
      mutation and cortical dysplasia.

PMID- 29033430
TI  - The Prevalence of Japanese Outpatients with Hypertension Who Meet the Definition
      of Treatment Resistant Hypertension and Are Eligible for Enrolment in Clinical
      Trials of Endovascular Ultrasound Renal Denervation.
AB  - Objective A clinical trial (REQUIRE) was started to investigate the use of an
      ultrasound renal denervation system in the treatment of resistant hypertension
      (RHT). We analyzed the prevalence of patients who were eligible for inclusion in
      this cross-sectional study at the time of screening. Methods Nine-hundred ninety
      nine consecutive hypertension (HT) patients who were treated in our hospital as
      outpatients were classified into the following categories: patients treated with
      at least 3 types of antihypertensive drugs including diuretic agents who were
      eligible for enrolment in SYMPLICITY HTN-Japan (SH-J) with an office systolic
      blood pressure (SBP) of >=160 mmHg, who were <=80 years of age, and an estimated
      glomerular filtration rate (eGFR) of >=45 mL/min/1.73 m2 (RHT-S); and patients
      who were treated similar medications and who were eligible for enrolment in
      REQUIRE, with an SBP of >=150 mmHg, <=75 years of age, and an eGFR of >=40
      mL/min/1.73 m2 (RHT-R). We investigated the proportion of patients in each
      category. We also investigated HT patients (1,423 cases) who were enrolled in the
      Chikushi Anti-Hypertension Trial (CHAT), a research network that includes general
      practitioners. Results Eleven patients (1.1%) with RHT-S and 18 patients (1.8%)
      with RHT-R were identified. After the exclusion of patients with secondary HT and
      a diastolic blood pressure (DBP) of <90 mmHg (applied in REQUIRE), 5 patients
      (0.5%) with RHT-S and 4 patients (0.4%) with RHT-R remained. In the analysis of
      the CHAT study, only 2 (0.1%) patients with RHT-R remained. Conclusion The number
      of eligible patients in the REQUIRE trial was decreased, largely due to the
      strict age restriction and the new DBP limitation. The prevalence of eligible
      patients in REQUIRE was estimated to be approximately 0.5 to 0.8 times that in SH
      J. Since patient enrollment will be difficult, drastic measures may be required
      to recruit eligible patients.

PMID- 29033431
TI  - Diagnostic Challenge in Pancreatic Sarcoidosis Using Endoscopic Ultrasonography.
AB  - We herein report a 55-year-old woman who presented with erythema and bilateral
      hilar lymphadenopathy 4 months prior to the detection of pancreatic lesions on an
      ultrasound. A skin biopsy showed evidence of sarcoidosis. The largest lesion in
      the tail of the pancreas was hypoechoic on endoscopic ultrasonography (EUS). The
      lesion was initially iso-enhanced on contrast enhanced-EUS (CE-EUS) but
      subsequently became hypoenhanced. The lesion revealed heterogeneous components of
      both soft and hard tissue on EUS elastography. She was ultimately diagnosed with
      pancreatic sarcoidosis based on the presence of noncaseating granulomas seen on
      pancreatic tissue retrieved through an EUS-guided fine needle aspiration biopsy.

PMID- 29033432
TI  - Drug-induced Brugada-type Electrocardiogram: A Cause of Sudden Death in Patients
      with Schizophrenia?

PMID- 29033433
TI  - Pneumothorax in a Patient with Unilateral Pulmonary Artery Agenesis.

PMID- 29033434
TI  - Hemoptysis from a Ruptured Saphenous Vein Graft Aneurysm.

PMID- 29033436
TI  - Bullous Pemphigoid Presenting with Esophagitis Dissecans Superficialis.

PMID- 29033435
TI  - Clinical Features of Nontuberculous Mycobacterial Pleurisy: A Review of 12 Cases.
AB  - Objective The incidence of pulmonary nontuberculous mycobacterial (NTM)
      infections has increased in recent decades. Nevertheless, NTM pleurisy is still a
      rare disease. The objective of the present study was to elucidate the clinical
      features and outcomes of NTM pleurisy. Methods A retrospective study was
      undertaken of consecutive patients whose pleural effusion culture yielded NTM,
      from 2002 to 2016 at a respiratory hospital in Japan. The clinical features,
      treatment, and outcomes of these patients were analyzed. Result The 12 patients
      with NTM pleurisy were predominantly male, with a median age of 69 years (range,
      48-93 years). They included eight patients with a history of smoking and six
      patients with immunosuppressive comorbidities such as malignancy, diabetes
      mellitus, and conditions requiring steroid administration. Fibrocavitary disease
      was the most common radiographic feature of these patients, and Mycobacterium
      avium complex was the most common pathogen. Pneumothorax was complicated in 11
      patients. Surgery was performed on seven patients, in addition to thoracic
      drainage for the treatment of pleurisy and pneumothorax. Three patients died of
      respiratory failure. Conclusion Pneumothorax is a frequent complication of NTM
      pleurisy, often making the condition difficult to treat. Surgery at an
      appropriate time should therefore considered for refractory cases.

PMID- 29033437
TI  - Acute Anorectal Thrombophlebitis Caused by a Protein C Deficiency.
AB  - A 46-year-old man visited the emergency department of our hospital with a 3-day
      history of anal pain, hemorrhaging, and a slight fever. He had previously been
      diagnosed with protein C deficiency and was prescribed dabigatran, a direct oral
      anticoagulant. Contrast-enhanced computed tomography showed severe rectal wall
      thickening with partial defect of enhancement. In addition, sigmoidoscopy
      revealed a dusky purplish swollen anorectal mucosa just above the dentate line.
      He was diagnosed with acute anorectal thrombophlebitis, and anticoagulant therapy
      with heparin was initiated. To our knowledge, this is the first case report of
      acute anorectal thrombophlebitis caused by protein C deficiency.

PMID- 29033438
TI  - Small-cell Lung Cancer Associated with SAPHO Syndrome.

PMID- 29033439
TI  - Trauma Wound Related Infection Caused by Enterobacter cancerogenus and Aeromonas
      hydrophilia.
AB  - We herein describe a case of trauma-related wound infection with a subcutaneous
      abscess caused by both Enterobacter cancerogenus and Aeromonas hydrophila. An 89
      year-old Japanese man was admitted to our hospital because of an injury that he
      had suffered in a car accident. The right dorsal region of the foot around the
      wound was reddish and swelling. The pus culture on his right foot grew E.
      cancerogenus and A. hydrophila. The patient was successfully treated with a 10
      day course of meropenem and a 25-day course of levofloxacin. E. cancerogenus can
      therefore be a causative pathogen in skin and soft tissue infections among trauma
      patients.

PMID- 29033440
TI  - Amiodarone-induced Thyrotoxicosis with Cardiopulmonary Arrest.
AB  - We describe a case of amiodarone-induced thyrotoxicosis (AIT) with
      cardiopulmonary arrest (CPA) in a 49-year-old woman. The patient had been treated
      with amiodarone for non-sustained ventricular tachycardia. Two weeks prior to her
      admission, she developed thyrotoxicosis and prednisolone (PSL, 30 mg daily) was
      administered with the continuation of amiodarone. However, she was admitted to
      our hospital for CPA. We performed total thyroidectomy to control her
      thyrotoxicosis and the pathological findings were consistent with type 2 AIT. She
      gradually improved and was discharged on day 84. This case demonstrates the
      importance of considering immediate total thyroidectomy for patients with
      uncontrollable AIT.

PMID- 29033441
TI  - Bilateral Tuberculous Pleurisy with Subsequent Upper Lobe Predominant Pulmonary
      Fibrosis Mimicking Pleuroparenchymal Fibroelastosis.
AB  - Although the majority of patients with Mycobacterium tuberculosis have pulmonary
      involvement, some cases have pleural involvement as extra-pulmonary sites of
      infection. We herein report a case of upper lobe-predominant pulmonary fibrosis
      that developed in a 47-year-old male with a history of bilateral tuberculous
      pleurisy. Based on his chest radiological findings, pleuroparenchymal
      fibroelastosis (PPFE) was most strongly suspected, and a surgical lung biopsy
      (SLB) was performed to obtain a pathological diagnosis. The SLB specimens showed
      interstitial pneumonia with pleural involvement without any characteristic
      findings of PPFE. Careful discretion in obtaining a precise diagnosis of this
      condition should be practiced in such cases.

PMID- 29033442
TI  - Efficacy of Oxycodone for Dyspnea in End-stage Heart Failure with Renal
      Insufficiency.
AB  - A 67-year-old man with dilated cardiomyopathy and renal insufficiency was
      admitted to our hospital with dyspnea secondary to end-stage heart failure. We
      introduced oxycodone for medically refractory dyspnea instead of morphine because
      of the patient's renal insufficiency. After the administration of oxycodone, his
      dyspnea was alleviated without any adverse opioid effects, such as respiratory
      depression. After treating his heart failure, he was able to leave the intensive
      care unit. Oxycodone may therefore be a reliable agent for the treatment of
      dyspnea in patients with end-stage heart failure and renal insufficiency.

PMID- 29033444
TI  - Endobronchial Lipoma: The Diagnostic Benefit of Computed Tomography Findings.

PMID- 29033443
TI  - Signet Ring Cell Carcinoma of Unknown Primary Origin Detected Incidentally by
      Lymph Node Purification for Thyroid Carcinoma.
AB  - A 63-year-old woman underwent thyroidectomy for papillary thyroid adenocarcinoma
      and cervical lymph node resection. Pathological analyses revealed the presence of
      signet cell carcinoma in a resected lymph node, which were apparently different
      from the pathological findings of thyroid carcinoma. No evidence of a primary
      tumor could be found elsewhere despite detailed examinations, including
      esophagogastroduodenoscopy, colonoscopy, capsule endoscopy, CT scan, and
      fluorodeoxyglucose-positron emission tomography. Two and half years later, the
      patient developed multiple bone metastases and the pathological findings
      confirmed the presence of signet cell carcinoma. The primary origin remained
      undetermined. Metastatic signet ring cell carcinoma of unknown primary origin is
      extremely rare.

PMID- 29033445
TI  - Auriculotemporal Nerve Syndrome.

PMID- 29033446
TI  - A Cerebral Air Embolism after Endoscopic Treatment.

PMID- 29033447
TI  - Inter-atrial Septal Thrombus without PFO.

PMID- 29033448
TI  - A Cardiac Calcified Amorphous Tumor Associated with End-stage Renal Disease: An
      Emerging Disease Concept.

PMID- 29033449
TI  - Symptomatology Patterns in Children with Allergic Rhinitis.
AB  - BACKGROUND Although allergic rhinitis (AR) is recognized as a growing global
      health disease with considerable importance for patients' lives, especially among
      children and adolescents, there is a lack of population studies concerning
      symptomatology patterns of the disease. The present study aimed to explore
      symptoms prevalence among school-aged children, to detect any correlation between
      allergen sensitivities with symptomatology patterns, and, finally, to evaluate
      the association of the sensitivity grade score with symptoms severity or
      seasonality. MATERIAL AND METHODS This was a cross-sectional, observational study
      in a childhood population. The first stage included recruitment of children and
      parental-completed questionnaires. The second stage included skin-prick tests for
      the most common allergens. Severity of symptoms was self-evaluated using a scale
      that ranged from "0" (no symptoms), "1" (mild), and "2" (moderate-to-severe). AR
      was classified as seasonal (SAR) or perennial (PAR). RESULTS The most frequent
      symptoms were reported for nasal obstruction, sneezing, and rhinorrhea. All nasal
      symptoms were significantly more profound among children with HDM sensitivity.
      However, more symptoms, not only nasal, but also ocular and general ones, were
      detected among patients with grass pollen sensitivity. Patients with PAR reported
      more severe symptoms. SAR was associated with mild disease. Finally, the
      sensitivity grade score was significantly correlated with symptom severity.
      CONCLUSIONS Our results suggest that allergen sensitivity may be correlated with
      symptomatology patterns among children who have allergic rhinitis.

PMID- 29033450
TI  - A Retrospective Chart Analysis with Follow-Up of Cogmed Working Memory Training
      in Children and Adolescents with Autism Spectrum Disorder.
AB  - BACKGROUND This case study was undertaken in an effort to assess whether
      children/adolescents with Autism Spectrum Disorder (ASD) experience improvement
      in comorbid ADHD following Cogmed Working Memory Training (CWMT). This treatment
      intervention has been shown to improve ADHD symptoms in children and adolescents;
      however, there have been no studies on its use with individuals with ASD.
      MATERIAL AND METHODS CWMT is a computer-based program that consists of 13
      auditory, visual, visual spatial, and combined exercises that are practiced for
      45 minutes a day, 5 days a week, for 5 weeks. Fifteen children/adolescents
      between the ages of 9 and 19 years with ASD and comorbid ADHD undertook a trial
      of CWMT. A 1-month follow-up and 2 longitudinal follow-ups were implemented.
      RESULTS The retrospective chart analysis and follow-up demonstrated improvement
      in attention and focus, impulsivity, emotional reactivity, and academic
      achievement in individuals with ASD and comorbid ADHD. Those benefits remained
      the same or increased over time. A number of participants also had benefits in
      their social interaction/social awareness. CONCLUSIONS CWMT has the potential to
      be an effective treatment intervention for children and adolescents with ASD
      because of its benign computer-based nature that seems to engage the unique
      learning style of this population. The authors hope that this paper will
      encourage others to study the ability of CWMT to be utilized in improving ADHD
      symptoms as well as social interaction/social awareness in individuals with ASD.

PMID- 29033452
TI  - Renal anaemia: iPSC-derived EPO-producing cells rescue anaemia.

PMID- 29033453
TI  - Polycystic kidney disease: Modulation of cystogenesis by the microenviroment.

PMID- 29033451
TI  - Dasatinib and Azacitidine Followed by Haploidentical Stem Cell Transplant for
      Chronic Myeloid Leukemia with Evolving Myelodysplasia: A Case Report and Review
      of Treatment Options.
AB  - BACKGROUND CML presenting with a variant Philadelphia translocation, atypical BCR
      ABL transcript, additional chromosomal aberrations, and evolving MDS is uncommon
      and therapeutically challenging. The prognostic significance of these genetic
      findings is uncertain, even as singular aberrations, with nearly no data on
      management and outcome when they coexist. MDS evolving during the course of CML
      may be either treatment-associated or an independently coexisting disease, and is
      generally considered to have an inferior prognosis. Tyrosine kinase inhibitors
      (TKI) directed against BCR-ABL are the mainstay of treatment for CML, whereas
      treatment modalities that may be utilized for MDS and CML include allogeneic stem
      cell transplant and - at least conceptually - hypomethylating agents. CASE REPORT
      Here, we describe the clinical course of such a patient, demonstrating that long
      term combined treatment with dasatinib and azacitidine for coexisting CML and MDS
      is feasible and well tolerated, and may be capable of slowing disease
      progression. This combination therapy had no deleterious effect on subsequent
      potentially curative haploidentical bone marrow transplantation. CONCLUSIONS The
      different prognostic implications of this unusual case and new therapeutic
      options in CML are discussed, together with a review of the current literature on
      CML presenting with different types of genomic aberrations and the coincident
      development of MDS. Additionally, this case gives an example of long-term
      combined treatment of tyrosine kinase inhibitors and hypomethylating agents,
      which could be pioneering in CML treatment.

PMID- 29033454
TI  - Gene regulation: Closing the loop on noisy gene expression.

PMID- 29033455
TI  - Genetic variation: Birds of a feather - genetic mapping of yellow pigmentation.

PMID- 29033458
TI  - Creating a Reliable, Cost-Effective ELISA Simulation.
AB  - The enzyme-linked immunosorbent assay (ELISA) is a fundamental laboratory
      technique with direct applications across scientific research and clinical
      diagnostics as well as everyday life. Unfortunately, many challenges exist that
      inhibit both its introduction and implementation in the high school biology
      classroom. We present a reliable yet inexpensive way of effectively simulating
      this assay, allowing student exposure to several advanced topics, including
      immunodetection, clinical diagnostics, and qualitative and quantitative
      colorimetric analysis.

PMID- 29033456
TI  - The DNA methyltransferase family: a versatile toolkit for epigenetic regulation.
AB  - The DNA methyltransferase (DNMT) family comprises a conserved set of DNA
      modifying enzymes that have a central role in epigenetic gene regulation. Recent
      studies have shown that the functions of the canonical DNMT enzymes - DNMT1,
      DNMT3A and DNMT3B - go beyond their traditional roles of establishing and
      maintaining DNA methylation patterns. This Review analyses how molecular
      interactions and changes in gene copy numbers modulate the activity of DNMTs in
      diverse gene regulatory functions, including transcriptional silencing,
      transcriptional activation and post-transcriptional regulation by DNMT2-dependent
      tRNA methylation. This mechanistic diversity enables the DNMT family to function
      as a versatile toolkit for epigenetic regulation.

PMID- 29033459
TI  - Instrumental variables as bias amplifiers with general outcome and confounding.
AB  - Drawing causal inference with observational studies is the central pillar of many
      disciplines. One sufficient condition for identifying the causal effect is that
      the treatment-outcome relationship is unconfounded conditional on the observed
      covariates. It is often believed that the more covariates we condition on, the
      more plausible this unconfoundedness assumption is. This belief has had a huge
      impact on practical causal inference, suggesting that we should adjust for all
      pretreatment covariates. However, when there is unmeasured confounding between
      the treatment and outcome, estimators adjusting for some pretreatment covariate
      might have greater bias than estimators without adjusting for this covariate.
      This kind of covariate is called a bias amplifier, and includes instrumental
      variables that are independent of the confounder, and affect the outcome only
      through the treatment. Previously, theoretical results for this phenomenon have
      been established only for linear models. We fill in this gap in the literature by
      providing a general theory, showing that this phenomenon happens under a wide
      class of models satisfying certain monotonicity assumptions. We further show that
      when the treatment follows an additive or multiplicative model conditional on the
      instrumental variable and the confounder, these monotonicity assumptions can be
      interpreted as the signs of the arrows of the causal diagrams.

PMID- 29033460
TI  - Mortality and morbidity in the 21st century.
AB  - We build on and extend the findings in Case and Deaton (2015) on increases in
      mortality and morbidity among white non-Hispanic Americans in midlife since the
      turn of the century. Increases in all-cause mortality continued unabated to 2015,
      with additional increases in drug overdoses, suicides, and alcohol-related liver
      mortality, particularly among those with a high-school degree or less. The
      decline in mortality from heart disease has slowed and, most recently, stopped,
      and this combined with the three other causes is responsible for the increase in
      all-cause mortality. Not only are educational differences in mortality among
      whites increasing, but from 1998 to 2015 mortality rose for those without, and
      fell for those with, a college degree. This is true for non-Hispanic white men
      and women in all five year age groups from 35-39 through 55-59. Mortality rates
      among blacks and Hispanics continued to fall; in 1999, the mortality rate of
      white non-Hispanics aged 50-54 with only a high-school degree was 30 percent
      lower than the mortality rate of blacks in the same age group but irrespective of
      education; by 2015, it was 30 percent higher. There are similar crossovers in all
      age groups from 25-29 to 60-64. Mortality rates in comparable rich countries have
      continued their pre-millennial fall at the rates that used to characterize the
      US. In contrast to the US, mortality rates in Europe are falling for those with
      low levels of educational attainment, and have fallen further over this period
      than mortality rates for those with higher levels of education. Many commentators
      have suggested that poor mortality outcomes can be attributed to contemporaneous
      levels of resources, particularly to slowly growing, stagnant, and even declining
      incomes; we evaluate this possibility, but find that it cannot provide a
      comprehensive explanation. In particular, the income profiles for blacks and
      Hispanics, whose mortality rates have fallen, are no better than those for
      whites. Nor is there any evidence in the European data that mortality trends
      match income trends, in spite of sharply different patterns of median income
      across countries after the Great Recession. We propose a preliminary but
      plausible story in which cumulative disadvantage from one birth cohort to the
      next, in the labor market, in marriage and child outcomes, and in health, is
      triggered by progressively worsening labor market opportunities at the time of
      entry for whites with low levels of education. This account, which fits much of
      the data, has the profoundly negative implication that policies, even ones that
      successfully improve earnings and jobs, or redistribute income, will take many
      years to reverse the mortality and morbidity increase, and that those in midlife
      now are likely to do much worse in old age than those currently older than 65.
      This is in contrast to an account in which resources affect health
      contemporaneously, so that those in midlife now can expect to do better in old
      age as they receive Social Security and Medicare. None of this implies that there
      are no policy levers to be pulled; preventing the over-prescription of opioids is
      an obvious target that would clearly be helpful.

PMID- 29033457
TI  - Emerging and evolving concepts in gene essentiality.
AB  - Gene essentiality is a founding concept of genetics with important implications
      in both fundamental and applied research. Multiple screens have been performed
      over the years in bacteria, yeasts, animals and more recently in human cells to
      identify essential genes. A mounting body of evidence suggests that gene
      essentiality, rather than being a static and binary property, is both context
      dependent and evolvable in all kingdoms of life. This concept of a non-absolute
      nature of gene essentiality changes our fundamental understanding of essential
      biological processes and could directly affect future treatment strategies for
      cancer and infectious diseases.

PMID- 29033461
TI  - Isotope-Labeled Aspartate Sidechain as a Non-Perturbing Infrared Probe:
      Application to Investigate the Dynamics of a Carboxylate Buried Inside a Protein.
AB  - Because of their negatively charged carboxylates, aspartate and glutamate are
      frequently found at the active or binding site of proteins. However, studying a
      specific carboxylate in proteins that contain multiple aspartates and/or
      glutamates via infrared spectroscopy is difficult due to spectral overlap. We
      show, herein, that isotopic-labeling of the aspartate sidechain can overcome this
      limitation as the resultant 13C=O asymmetric stretching vibration resides in a
      transparent region of the protein IR spectrum. Applicability of this site
      specific vibrational probe is demonstrated by using it to assess the dynamics of
      an aspartate ion buried inside a small protein via two-dimensional infrared
      spectroscopy.

PMID- 29033462
TI  - Acculturative Stress, Psychological Distress, and Religious Coping Among Latina
      Young Adult Immigrants.
AB  - Religion is a source of strength in Latina/o culture during challenging life
      transitions, such as the immigration process. Guided by a sociological stress
      process model, this study examines relations between dimensions of religious
      coping, acculturative stress, and psychological distress among 530 young Latina
      women (ages 18-23 years) who recently immigrated to the United States (i.e.,
      approximately 12 months prior to assessment). Higher levels of acculturative
      stress were associated with higher levels of psychological distress. Negative
      religious coping (i.e., the tendency to struggle with faith) moderated the
      relation between acculturative stress and psychological distress. Participants
      experiencing higher levels of acculturative stress reported greater psychological
      distress when they indicated more negative religious coping. Positive religious
      coping (i.e., the tendency to relate to faith with comfort and certainty) was not
      linked with acculturative stress or psychological distress. Implications for
      culturally tailored counseling interventions for this underserved and
      understudied population are discussed.

PMID- 29033463
TI  - An Examination of the Most Recent Episode of Molly Use among College Students.
AB  - OBJECTIVE: The current study examined event-level characteristics (e.g.,
      contextual factors, risk behaviors) during the most recent episode of Molly use
      among a sample of college students who reported previously using Molly.
      PARTICIPANTS: Participants (N = 151; 66.7% female) were drinkers aged 18 to 25.
      Data were collected from October to November 2014, February to April 2015, and
      September to November 2015. METHOD: Participants completed measures regarding
      typical Molly use and items related to context and behaviors during their most
      recent episode of Molly use. RESULTS: Findings revealed that our sample most
      commonly reported using Molly earlier in the evening while hanging out with
      friends or at a party. Additionally, sexual and other drug use behaviors commonly
      occurred when using Molly. CONCLUSIONS: Findings provide preliminary information
      in guiding future work exploring Molly use and potential substance-related issues
      associated with the context of when and how Molly is consumed.

PMID- 29033464
TI  - Beyond Orphanhood: Parental Nonresidence and Child Well-being in Tanzania.
AB  - This article used data from the Rufiji Health and Demographic Surveillance System
      in Tanzania to examine the influence of parental non-residence on child survival
      and school entry. Using survival analysis methods, the article tested variations
      by parent and by cause, examining parental death, non-residence due to parental
      relationship status, and migration. In general, maternal non-residence was more
      consequential for child survival, while paternal non-residence influences school
      entry. This is consistent with gendered parenting patterns in the setting. There
      was important variation by cause and by outcome, particularly for paternal non
      residence. Paternal non-residence due to non-marital birth was associated with
      increased risk of child death, while paternal migration was associated with
      improved survival. Paternal death and migration were associated with lower odds
      of school entry. This article moves beyond orphanhood to consider multiple causes
      of parental non-residence simultaneously, demonstrating that parental non
      residence is not uniformly deleterious for children.

PMID- 29033465
TI  - Parental Modeling and Deidentification in Romantic Relationships Among Mexican
      origin Youth.
AB  - This study investigated youth's modeling of and de-identification from parents in
      romantic relationships, using two phases of data from adolescent siblings,
      mothers, and fathers in 246 Mexican-origin families. Each parent reported his/her
      marital satisfaction and conflict, and youth reported on parent-adolescent warmth
      and conflict at Time 1. Youth's reports of modeling of and de-identification from
      their mothers and fathers and three romantic relationship outcomes were assessed
      at Time 2. Findings revealed that higher parental marital satisfaction, lower
      marital conflict, and higher warmth and lower conflict in parent-adolescent
      relationships were associated with more modeling and less de-identification from
      parents. Moreover, higher de-identification was linked to a greater likelihood of
      youth being involved in a romantic relationship and cohabitation, whereas more
      modeling was linked to a lower likelihood of cohabitation and older age of first
      sex. Discussion underscores the importance of assessing parental modeling and de
      identification and understanding correlates of these processes.

PMID- 29033466
TI  - Silane-Acrylate Chemistry for Regulating Network Formation in Radical
      Photopolymerization.
AB  - Photoinitiated silane-ene chemistry has the potential to pave the way toward
      spatially resolved organosilicon compounds, which might find application in
      biomedicine, microelectronics, and other advanced fields. Moreover, this approach
      could serve as a viable alternative to the popular photoinitiated thiol-ene
      chemistry, which gives access to defined and functional photopolymer networks. A
      difunctional bis(trimethylsilyl)silane with abstractable hydrogens (DSiH) was
      successfully synthesized in a simple one-pot procedure. The radical reactivity of
      DSiH with various homopolymerizable monomers (i.e., (meth)acrylate, vinyl ester,
      acrylamide) was assessed via 1H NMR spectroscopic studies. DSiH shows good
      reactivity with acrylates and vinyl esters. The most promising silane-acrylate
      system was further investigated in cross-linking formulations toward its
      reactivity (e.g., heat of polymerization, curing time, occurrence of gelation,
      double-bond conversion) and compared to state-of-the-art thiol-acrylate resins.
      The storage stability of prepared resin formulations is greatly improved for
      silane-acrylate systems vs thiol-ene resins. Double-bond conversion at the gel
      point (DBCgel) and overall DBC were increased, and polymerization-induced
      shrinkage stress has been significantly reduced with the introduction of silane
      acrylate chemistry. Resulting photopolymer networks exhibit a homogeneous network
      architecture (indicated by a narrow glass transition) that can be tuned by
      varying silane concentration, and this confirms the postulated regulation of
      radical network formation. Similar to thiol-acrylate networks, this leads to more
      flexible photopolymer networks with increased elongation at break and improved
      impact resistance. Additionally, swelling tests indicate a high gel fraction for
      silane-acrylate photopolymers.

PMID- 29033467
TI  - Poly(ethylene glycol)s in Semidilute Regime: Radius of Gyration in the Bulk and
      Partitioning into a Nanopore.
AB  - Using two approaches, small-angle neutron scattering (SANS) from bulk solutions
      and nanopore conductance-fluctuation analysis, we studied structural and dynamic
      features of poly(ethylene glycol) (PEG) water/salt solutions in the dilute and
      semidilute regimes. SANS measurements on PEG 3400 at the zero-average contrast
      yielded the single chain radius of gyration (Rg) over 1-30 wt %. We observed a
      small but statistically reliable decrease in Rg with increasing PEG
      concentration: at 30 wt % the chain contracts by a factor of 0.94. Analyzing
      conductance fluctuations of the alpha-hemolysin nanopore in the mixtures of PEG
      200 with PEG 3400, we demonstrated that polymer partitioning into the nanopore is
      mostly due to PEG 200. Specifically, for a 1:1 wt/wt mixture the smaller polymer
      dominates to the extent that only about 1/25 of the nanopore volume is taken by
      the larger polymer. These findings advance our conceptual and quantitative
      understanding of nanopore polymer partitioning; they also support the main
      assumptions of the recent "polymers-pushing-polymers" model.

PMID- 29033468
TI  - The Aviation Paradox: Why We Can 'Know' Jetliners But Not Reactors.
AB  - Publics and policymakers increasingly have to contend with the risks of complex,
      safety-critical technologies, such as airframes and reactors. As such,
      'technological risk' has become an important object of modern governance, with
      state regulators as core agents, and 'reliability assessment' as the most
      essential metric. The Science and Technology Studies (STS) literature casts doubt
      on whether or not we should place our faith in these assessments because
      predictively calculating the ultra-high reliability required of such systems
      poses seemingly insurmountable epistemological problems. This paper argues that
      these misgivings are warranted in the nuclear sphere, despite evidence from the
      aviation sphere suggesting that such calculations can be accurate. It explains
      why regulatory calculations that predict the reliability of new airframes cannot
      work in principle, and then it explains why those calculations work in practice.
      It then builds on this explanation to argue that the means by which engineers
      manage reliability in aviation is highly domain-specific, and to suggest how a
      more nuanced understanding of jetliners could inform debates about nuclear
      energy.

PMID- 29033469
TI  - A Bootstrap Metropolis-Hastings Algorithm for Bayesian Analysis of Big Data.
AB  - Markov chain Monte Carlo (MCMC) methods have proven to be a very powerful tool
      for analyzing data of complex structures. However, their computer-intensive
      nature, which typically require a large number of iterations and a complete scan
      of the full dataset for each iteration, precludes their use for big data
      analysis. In this paper, we propose the so-called bootstrap Metropolis-Hastings
      (BMH) algorithm, which provides a general framework for how to tame powerful MCMC
      methods to be used for big data analysis; that is to replace the full data log
      likelihood by a Monte Carlo average of the log-likelihoods that are calculated in
      parallel from multiple bootstrap samples. The BMH algorithm possesses an
      embarrassingly parallel structure and avoids repeated scans of the full dataset
      in iterations, and is thus feasible for big data problems. Compared to the
      popular divide-and-combine method, BMH can be generally more efficient as it can
      asymptotically integrate the whole data information into a single simulation run.
      The BMH algorithm is very flexible. Like the Metropolis-Hastings algorithm, it
      can serve as a basic building block for developing advanced MCMC algorithms that
      are feasible for big data problems. This is illustrated in the paper by the
      tempering BMH algorithm, which can be viewed as a combination of parallel
      tempering and the BMH algorithm. BMH can also be used for model selection and
      optimization by combining with reversible jump MCMC and simulated annealing,
      respectively.

PMID- 29033470
TI  - ANIMAL MIGRATION AS A MOVING TARGET FOR CONSERVATION: INTRA-SPECIES VARIATION AND
      RESPONSES TO ENVIRONMENTAL CHANGE, AS ILLUSTRATED IN A SOMETIMES MIGRATORY
      SONGBIRD.
AB  - Identifying important "migratory species" and the characteristics of their
      migrations might sound like a simple starting point for efforts to conserve and
      protect animal migrations. However, migrations are dynamic phenomena that vary
      over space and time, and migratory behaviors can vary substantially among closely
      related species, subspecies, races, or populations, and even among individual
      animals within a single population. The migratory behaviors of populations or
      individuals can also change rapidly-or be lost entirely-in response to habitat
      alteration or climate change. These complexities present both challenges and
      opportunities for initiatives to conserve animal migrations. In this Article, we
      discuss the concepts of intra-species variation in migration and the sensitivity
      of migrations to environmental change, and we consider the implications of these
      topics for legal, policy, management, and research agendas.

PMID- 29033471
TI  - Using Twitter for Demographic and Social Science Research: Tools for Data
      Collection and Processing.
AB  - Despite recent and growing interest in using Twitter to examine human behavior
      and attitudes, there is still significant room for growth regarding the ability
      to leverage Twitter data for social science research. In particular, gleaning
      demographic information about Twitter users-a key component of much social
      science research-remains a challenge. This article develops an accurate and
      reliable data processing approach for social science researchers interested in
      using Twitter data to examine behaviors and attitudes, as well as the demographic
      characteristics of the populations expressing or engaging in them. Using
      information gathered from Twitter users who state an intention to not vote in the
      2012 presidential election, we describe and evaluate a method for processing data
      to retrieve demographic information reported by users that is not encoded as text
      (e.g., details of images) and evaluate the reliability of these techniques. We
      end by assessing the challenges of this data collection strategy and discussing
      how large-scale social media data may benefit demographic researchers.

PMID- 29033472
TI  - HISTOPATHOLOGICAL ANALYSIS OF THE F344 RAT LUNG UPON EXPOSURE TO RETENOIC ACID,
      OVALBUMIN, MOLD SPORES AND CITRAL.
AB  - The paradoxical role of retinoic acid (All Trans Retinoic Acid; ATRA) in the
      development of allergic and/or inflammatory complications in contrast to a
      therapeutic modality for lung pathology is not well understood or established in
      the literature. As well, the role of Citral (inhibitor of retinoid function; a
      non-toxic chemical that exists in two forms (diethyl; C1 or cis-trans dimethyl;
      C2), in the reversal of retinoic acid, ovalbumin and allergic mold spore
      pathophysiology is also not well ascertained under an in vivo setting. Therefore,
      it is hypothesized that exposure of F344 lung tissues to supra-physiologic levels
      of retinoic acid, ovalbumin and mold spores individually or in combination with
      each other will lead to inflammatory tissue pathology and that Citral 1 and 2
      will reverse or ameliorate the related pathological damage to lung tissues. Even
      though ovalbumin and retinoic acid have been previously applied through intra
      tracheal route in cancer prevention and immunological research, the objective of
      this study was to evaluate the histopathological implications of such exposure in
      vivo. This IACUC approved in vivo study used Fischer 344 rats (n = 80 ; 229 to
      273g), which were randomly assigned to controls as well as ovalbumin and mold
      sensitized treatment groups (0.80 mg/kg and 1*109 mold spores combined from 4
      strains/100 MUl intra-tracheal; all others were dosed by intra-peritoneal
      injection at days 1 and 7 with 80 mg/kg each of ATRA as well as 20 and 50 mg/kg
      each of Citrals 1 or 2 individually or in combination to represent all four
      chemicals and mold spores treatments. Positive and negative controls for each
      treatment were also included in the study. Animals were housed in rat cages at
      the JSU Research Animal Core Facilities and were placed on a 12:12 light-dark
      cycle. A standard rodent diet and water access were provided ad libidum. All
      animals were sacrificed on day 21 and lung tissues were processed for
      histopathology. Slides were prepared and were digitized for comparison of tissues
      pathology. Results showed that exposure of the F344 rats to ovalbumin and ATRA
      showed various levels of lung tissue damage that was ameliorated by Citral 2 in
      combination. Mold and ATRA exposure caused various levels of lung tissue damage
      that was reversed by C1 in combination with each other. Taken together, the study
      showed that there are variable pathologic inflammatory responses from the
      interaction of ovalbumin, Citrals, mold spores and retinoic acid, and that the
      addition of Citrals have reversed lung tissue pathologies. These findings
      warrants further investigation as to the actual role of these interactions in
      relation to acute/chronic lung disease and the possibility of reversing retinoid
      mediated pathologies in the Fisher rat model.

PMID- 29033473
TI  - IMPACT OF ATRA ON OVALBUMIN AND MOLD-SENSITIZED F344 RATS AND REVERSAL OF HEALTH
      RELATED IMPLICATIONS BY CITRAL.
AB  - The role of retinoic acid (All Trans Retinoic Acid; ATRA) in the development of
      hypervitaminosis A pathophysiology is not well understood or established in the
      literature. As well, the role of Citral (inhibitor of retinoid function; a non
      toxic chemical that exists in two forms (diethyl; C1 or cis-trans dimethyl; C2).)
      in the reversal of pathophysiological implications is also not ascertained under
      an in vivo setting. Therefore, it is hypothesized that ovalbumin exposure will
      sensitize the body to supra-physiologic levels of retinoic acid leading to a
      negative pathophysiological impact and that Citrals 1 and 2 will reverse or
      ameliorate the related damage to the body's pathophysiology. Even though
      ovalbumin and retinoic have been previously applied through intra-tracheal route
      in cancer prevention and immunological research, the objective of this study was
      to evaluate their interaction as a remedy for hypervitaminosis A. This IACUC
      approved in vivo study used Fischer 344 rats (n = 80 ;229 to 273g), which were
      randomly assigned to controls as well as ovalbumin and mold-sensitized treatment
      groups (0.80 mg/kg and 1X109 mold spores combined from 4 strains/100 MUl intra
      tracheal; all others were dosed by intra-peritoneal injection at days 1 and 7
      with 80 mg/kg each of ATRA as well as 20 and 50 mg/kg each of Citrals 1 or 2
      individually or in combination to represent all four chemicals and mold spores
      treatments.. Positive and negative controls for each treatment were also included
      in the study. Animals were housed in rat cages at the JSU Research Animal Core
      Facilities and were placed on a 12:12 light dark cycle. A standard rodent diet
      and water access were provided ad-libidum. Rat weights were recorded on day 1 and
      21, all animals were sacrificed on day 21 and blood was collected and processed
      for hematological parameters. Results showed that even though C1 and C2 were not
      toxic individually, their combination at high dosing was lethal. Exposure of
      ovalbumin-sensitized rats to ATRA showed various levels of weight losses and
      negative hematological implications that were ameliorated by exposure to Citrals
      at various combinations with retinoic acid. Taken together, the study showed that
      there are variable pathophysiological responses from the interaction of
      ovalbumin, mold spores and retinoic acid and that Citrals were found to be
      individually effective in reversing health-related pathophysiologies. These
      findings warrants further investigations as to the actual role of these
      interactions in relation to acute pathophysiologic health implications and the
      possibility of reversing hypervitaminosis A-mediated health-related impacts.

PMID- 29033474
TI  - Operation of a 140 GHz Gyro-amplifier using a Dielectric-loaded, Sever-less
      Confocal Waveguide.
AB  - The design and experimental results of a 140 GHz gyro-amplifier that uses a
      dielectric-loaded, sever-less confocal waveguide are presented. The gyro
      traveling wave amplifier uses the HE06 mode of a confocal geometry with power
      coupled in and out of the structure with Vlasov-type, quasi-optical couplers.
      Dielectric loading attached to the side of the confocal structure suppresses
      unwanted modes allowing zero-drive stable operation at 48 kV and 3A of beam
      current. The confocal gyro-amplifier demonstrated a peak circuit gain of 35 dB, a
      bandwidth of 1.2 GHz and a peak output power of 550 W at 140.0 GHz.

PMID- 29033475
TI  - The association between the MAOA 2R genotype and delinquency over time among men:
      the interactive role of parental closeness and parental incarceration.
AB  - Using a panel of 6,001 males from the National Longitudinal Study of Adolescent
      and Adult Health, we examine potential moderation by paternal incarceration and
      parent-child closeness altering the relationship between the rare 2R MAOA
      genotype and delinquency. By jointly examining moderation patterns for both the
      mother and father with the transmission of the MAOA genotype from mother to son,
      we are able to make inferences about the specific genetic model that best
      explains these outcomes. In line with prior research, we find a direct
      relationship between the MAOA 2R genotype and delinquency, independent of
      parental incarceration and closeness. Examining moderation patterns, we find that
      delinquency risk for the 2R allele is buffered for males close to their
      biological or social father, but not their biological mother. We conclude that
      the 2R delinquency association is not due to passive gene-environment correlation
      but is best characterized as a social control gene-environment interaction.

PMID- 29033476
TI  - Exploratory Item Classification Via Spectral Graph Clustering.
AB  - Large-scale assessments are supported by a large item pool. An important task in
      test development is to assign items into scales that measure different
      characteristics of individuals, and a popular approach is cluster analysis of
      items. Classical methods in cluster analysis, such as the hierarchical
      clustering, K-means method, and latent-class analysis, often induce a high
      computational overhead and have difficulty handling missing data, especially in
      the presence of high-dimensional responses. In this article, the authors propose
      a spectral clustering algorithm for exploratory item cluster analysis. The method
      is computationally efficient, effective for data with missing or incomplete
      responses, easy to implement, and often outperforms traditional clustering
      algorithms in the context of high dimensionality. The spectral clustering
      algorithm is based on graph theory, a branch of mathematics that studies the
      properties of graphs. The algorithm first constructs a graph of items,
      characterizing the similarity structure among items. It then extracts item
      clusters based on the graphical structure, grouping similar items together. The
      proposed method is evaluated through simulations and an application to the
      revised Eysenck Personality Questionnaire.

PMID- 29033477
TI  - Is Lhasa Tibetan Sign Language emerging, endangered, or both?
AB  - This article offers the first overview of the recent emergence of Tibetan Sign
      Language (TibSL) in Lhasa, capital of the Tibet Autonomous Region (TAR), China.
      Drawing on short anthropological fieldwork, in 2007 and 2014, with people and
      organisations involved in the formalisation and promotion of TibSL, the author
      discusses her findings within the nine-fold UNESCO model for assessing linguistic
      vitality and endangerment. She follows the adaptation of this model to assess
      signed languages by the Institute of Sign Languages and Deaf Studies (iSLanDS) at
      the University of Central Lancashire. The appraisal shows that TibSL appears to
      be between "severely" and "definitely" endangered, adding to the extant studies
      on the widespread phenomenon of sign language endangerment. Possible future
      influences and developments regarding the vitality and use of TibSL in Central
      Tibet and across the Tibetan plateau are then discussed and certain additions,
      not considered within the existing assessment model, suggested. In concluding,
      the article places the situation of TibSL within the wider circumstances of
      minority (sign) languages in China, Chinese Sign Language (CSL), and the post
      2008 movement to promote and use "pure Tibetan language".

PMID- 29033478
TI  - Bayesian variable selection for a semi-competing risks model with three hazard
      functions.
AB  - A variable selection procedure is developed for a semi-competing risks regression
      model with three hazard functions that uses spike-and-slab priors and stochastic
      search variable selection algorithms for posterior inference. A rule is devised
      for choosing the threshold on the marginal posterior probability of variable
      inclusion based on the Deviance Information Criterion (DIC) that is examined in a
      simulation study. The method is applied to data from esophageal cancer patients
      from the MD Anderson Cancer Center, Houston, TX, where the most important
      covariates are selected in each of the hazards of effusion, death before
      effusion, and death after effusion. The DIC procedure that is proposed leads to
      similar selected models regardless of the choices of some of the hyperparameters.
      The application results show that patients with intensity-modulated radiation
      therapy have significantly reduced risks of pericardial effusion, pleural
      effusion, and death before either effusion type.

PMID- 29033479
TI  - Status Concern and Relative Deprivation in China: Measures, Empirical Evidence
      and Economic and Policy Implications.
AB  - Status concern and feelings of relative deprivation affect individual behaviour
      and well-being. Traditional norms and the alarming inequality in China have made
      relative deprivation increasingly intense for the Chinese population. This
      article reviews empirical literature on China that attempts to test the relative
      deprivation hypothesis, and also reviews the origins and pathways of relative
      deprivation, compares its economic measures in the literature and summarises the
      scientific findings. Drawing from solid empirical evidence, the author discusses
      the important policy implications on redistribution, official regulations and
      grassroots sanctions, and relative poverty alleviation.

PMID- 29033480
TI  - Photopharmacology.

PMID- 29033481
TI  - Adverse drug reaction monitoring in patients on antiretroviral therapy in a
      tertiary care hospital in Eastern India.
AB  - BACKGROUND: Besides unparalleled benefits, highly active antiretroviral therapy
      is also associated with wide range of potential adverse drug reactions (ADRs),
      which hinders treatment adherence. The present study was thus designed to monitor
      and explore the pattern of occurrence of ADRs to various antiretroviral therapy
      (ART) regimens in a tertiary care ART setup. MATERIALS AND METHODS: A
      prospective, observational clinical study was carried out in the outpatient
      setting of nodal ART center of Eastern India. A total of 610 patients on various
      ART regimens were studied for suspected ADRs over 12 months. Adverse event
      history, medication history, and other relevant details were captured. Causality
      and severity of each reported ADR were duly assessed. RESULTS: 32.45% patients of
      total study participants presented with a total of 330 ADRs. Patients from
      zidovudine-based regimens presented with majority of ADRs such as anemia (up to
      36%), central nervous system (CNS), and gastrointestinal (GI) side effects.
      Tenofovir-based regimens were, however, found to be mildly safer. The combination
      with Efavirenz was associated with majorly CNS side effects while that of
      nevirapine was associated with rash and pigmentation of nails. Atazanavir boosted
      second-line regimens were notably associated with increased serum lipid levels
      followed by other GI and CNS adverse effects. Increased liver enzymes were found
      in atazanavir-based second-line ART. CONCLUSION: The study enables to obtain
      information on the incidence and pattern of ADRs associated with various
      antiretroviral regimens, thereby reducing its occurrence and protecting the
      patient population from avoidable harm. Need of intensive monitoring for ADRs in
      ARTs thus seems to be a mandate.

PMID- 29033482
TI  - In vitro antioxidant and in vivo antidepressant activity of green synthesized
      azomethine derivatives of cinnamaldehyde.
AB  - OBJECTIVES: In this study, three (CS-1 to CS-3) azomethine derivatives of
      cinnamaldehyde were green synthesized, characterized, and their antioxidant and
      antidepressant activities were explored. MATERIALS AND METHODS: The antioxidant
      effect of these compounds was initially performed in vitro using 1,1-diphenyl-2
      picrylhydrazyl (DPPH) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid)
      (ABTS) assay methods before subjecting them to in vivo experiments. Compounds
      showing potent antioxidant activity (CS-1 and CS-2) were investigated further for
      their antidepressant activity using the forced swim test (FST) and tail
      suspension test (TST). Ascorbic acid (AA) and fluoxetine (20 mg/kg, p.o) were
      used as reference drugs for comparison in the antioxidant and antidepressant
      experiments, respectively. RESULTS: It was observed that CS-2 and CS-3 exhibited
      highest DPPH (half maximal inhibitory concentration [IC50]: 16.22 and 25.18
      MUg/mL) and ABTS (IC50: 17.2 and 28.86 MUg/mL) radical scavenging activity,
      respectively, compared to AA (IC50: 15.73 and 16.79 MUg/mL) and therefore, both
      CS-2 and CS-3 were tested for their antidepressant effect using FST and TST as
      experimental models. Pretreatment of CS-2 and CS-3 (20 mg/kg) for 10 days
      considerably decreased the immobility time in both the FST and TST models.
      CONCLUSION: The antioxidant and antidepressant effect of CS-2 and CS-3 may be
      attributed to the presence of azomethine linkage in the molecule.

PMID- 29033483
TI  - The impact of antidepressant treatment on brain-derived neurotrophic factor
      level: An evidence-based approach through systematic review and meta-analysis.
AB  - OBJECTIVES: Antidepressant treatment alters brain-derived neurotrophic factor
      (BDNF) levels, but it is not well established whether BDNF can be used as a
      marker to prove the efficacy of antidepressant treatment. The present systematic
      review and meta-analysis aim at assessing the influence of antidepressant
      treatment on BDNF level and the Hamilton Depression Rating Scale (HDRS) score,
      thereby to establish the rationale of utilizing BDNF as a predictive biomarker
      and HDRS score as an indicator for antidepressant treatment efficacy. MATERIALS
      AND METHODS: Search was conducted in PubMed, Science Direct, and Cochrane
      databases using the key words "BDNF" and "Depression" and "Antidepressants." On
      the basis of the inclusion and exclusion criteria, studies were filtered and
      finally 6 randomized controlled trials were shortlisted. RESULTS: Comparison of
      serum BDNF level before and after antidepressant treatment was performed and the
      result showed that antidepressant treatment does not significantly affect the
      BDNF levels (confidence interval [CI]: -0.483 to 0.959; standard mean difference
      [SMD]: 0.238, P = 0.518). Egger's regression test (P = 0.455) and heterogeneity
      test (I2 = 88.909%) were done. Similarly, comparison of HDRS scores before and
      after antidepressant treatment indicated improvement in HDRS score suggesting
      positive outcome (CI: 1.719 to 3.707; SMD: 2.713, P < 0.001). Egger's regression
      test (P = 0.1417) and heterogeneity test (I2 = 89.843%) were performed.
      Publication bias was observed by funnel plot. CONCLUSION: Changes in BDNF levels
      do not occur uniformly for all the antidepressants. Hence, to use BDNF as a
      biomarker, it needs to be seen whether the same is true for all antidepressants.

PMID- 29033485
TI  - Correlation of long-term glycemic control as measured by glycated hemoglobin with
      serum angiopoietin-like 6 protein levels in type 2 diabetes mellitus patients.
AB  - AIMS: Angiopoietin-like growth factors (ANGPTLs) regulate glucose, lipid
      homeostasis, and insulin sensitivity. This study aimed to find whether long-term
      glycemic control (glycated hemoglobin [HbA1c]) has any correlation with serum
      ANGPTL6 levels in patients of type 2 diabetes mellitus. MATERIALS AND METHODS: It
      was an open-label, observational, prospective clinical study. Sixty-five
      participants (41 diabetic patients receiving daily dose of oral metformin for a
      minimum of 3 months and 24 matched controls) completed the study. A single venous
      blood sample was taken from each participant to determine serum HbA1c and serum
      ANGPTL6 levels. Comparison of serum ANGPTL6 levels according to the HbA1c levels,
      in groups A, B, and C ranging from 6.5%-8%, 8.1%-9.5%, and >9.5%, respectively,
      was done using Kruskal-Wallis H-test followed by pairwise comparisons. RESULTS:
      Serum HbA1c and serum ANGPTL6 levels were raised significantly (P < 0.05) in
      diabetic patients when compared with control participants. A positive correlation
      was observed between serum HbA1c and serum ANGPTL6 levels (r = 0.88, 95%
      confidence interval 0.81, 0.92). Mean ANGPTL6 level for Group A (n = 20) was
      394.3 pg/ml, for Group B (n = 8) 692.8 pg/ml, and for Group C (n = 13) 896.2
      pg/ml. CONCLUSIONS: Serum ANGPTL6 levels were significantly higher in type 2
      diabetic patients in comparison with healthy controls. Poor glycemic control in
      diabetes mellitus as reflected by higher serum HbA1c levels is associated with
      raised serum ANGPTL6 levels.

PMID- 29033484
TI  - Congenital malformation and autism spectrum disorder: Insight from a rat model of
      autism spectrum disorder.
AB  - AIMS AND OBJECTIVES: The primary aim was an evaluation of the pattern of gross
      congenital malformations in a rat model of autism spectrum disorder (ASD) and the
      secondary aim was characterization of the most common gross malformation
      observed. MATERIALS AND METHODS: In females, the late pro-oestrous phase was
      identified by vaginal smear cytology, and then, they were allowed to mate at 1:3
      ratio (male: female). Pregnancy was confirmed by the presence of sperm plug in
      the vagina and presence of sperm in the vaginal smear. In the ASD group, ASD was
      induced by injecting valproic acid 600 mg/kg (i.p.) to pregnant female rats (n =
      18) on day 12.5 (single injection). Only vehicle (normal saline) was given in the
      control group (n = 12). After delivery, pups were grossly observed for congenital
      malformations until the time of sacrifice (3 months) and different types of
      malformations and their frequency were noted and characterized. RESULTS: In the
      ASD group, congenital malformation was present in 69.9% of the pups, whereas in
      the control group, it was 0%. Male pups were most commonly affected (90% in males
      vs. only 39.72% in female pups). The tail deformity was the most common
      malformation found affecting 61.2% pups in the ASD group. Other malformations
      observed were dental malformation (3.82%), genital malformation (3.28%) and paw
      malformation (1.1%). Hind limb paralysis was observed in one pup. The tail
      anomalies were characterized as per gross appearance and location of the
      malformation. CONCLUSION: In this well-validated rat model of ASD, congenital
      malformation was quite common. It seems screening of congenital malformations
      should be an integral part of the management of ASD, or the case may be vice
      versa, i.e., in the case of a baby born with a congenital deformity, they should
      be screened for ASD.

PMID- 29033488
TI  - Automated Liver Elasticity Calculation for 3D MRE.
AB  - Magnetic Resonance Elastography (MRE) is a phase-contrast MRI technique which
      calculates quantitative stiffness images, called elastograms, by imaging the
      propagation of acoustic waves in tissues. It is used clinically to diagnose liver
      fibrosis. Automated analysis of MRE is difficult as the corresponding MRI
      magnitude images (which contain anatomical information) are affected by intensity
      inhomogeneity, motion artifact, and poor tissue- and edge-contrast. Additionally,
      areas with low wave amplitude must be excluded. An automated algorithm has
      already been successfully developed and validated for clinical 2D MRE. 3D MRE
      acquires substantially more data and, due to accelerated acquisition, has
      exacerbated image artifacts. Also, the current 3D MRE processing does not yield a
      confidence map to indicate MRE wave quality and guide ROI selection, as is the
      case in 2D. In this study, extension of the 2D automated method, with a simple
      wave-amplitude metric, was developed and validated against an expert reader in a
      set of 57 patient exams with both 2D and 3D MRE. The stiffness discrepancy with
      the expert for 3D MRE was -0.8% +/- 9.45% and was better than discrepancy with
      the same reader for 2D MRE (-3.2% +/- 10.43%), and better than the inter-reader
      discrepancy observed in previous studies. There were no automated processing
      failures in this dataset. Thus, the automated liver elasticity calculation (ALEC)
      algorithm is able to calculate stiffness from 3D MRE data with minimal bias and
      good precision, while enabling stiffness measurements to be fully reproducible
      and to be easily performed on the large 3D MRE datasets.

PMID- 29033486
TI  - Topiramate-induced acute liver injury: A rare adverse effect.
AB  - Idiosyncratic drug-induced liver injury (DILI) is damage to liver occurring at
      recommended dose of a drug in contrast to toxic or predictable DILI. Although it
      is common in first-generation antiepileptic drugs (AEDs), it is rare in newer
      AEDs such as topiramate. Topiramate commonly causes neurological adverse effects
      such as psychomotor slowing and somnolence. Hepatotoxicity by topiramate is rare
      and has been previously reported in combination with other drugs such as
      valproate and carbamazepine. Here, we report a case of topiramate-induced
      asymptomatic elevation of liver enzymes in an adult man diagnosed with alcohol
      dependence syndrome and alcohol withdrawal complicated with seizures.

PMID- 29033487
TI  - Gingival hyperplasia: Should drug interaction be blamed for?
AB  - Gingival overgrowth (GO) is one of the common findings in clinical practice.
      There could be several causes including drugs associated with the GO.
      Carbamazepine (CBZ) and amlodipine are the drugs which are infrequently
      documented as a cause in inducing the gingival hyperplasia. Certain drugs in the
      body fluid might limit the population of plaque bacteria and alter their
      metabolism that in turn induce the inflammatory mediators and also activate the
      genetic and biochemical factors responsible for gingival fibroblast growth. Drug
      induced GO is a side effect with a multifactorial etiology that seems to
      orchestrate the interaction between drugs and fibroblasts in the gingiva. We
      describe a case of trigeminal neuralgia with hypertension treated with multiple
      drugs including amlodipine and CBZ. Although amlodipine is known to be
      infrequently associated with GO, an association of CBZ with GO is even rarer.
      Causality analysis on the World Health Organization Uppsala Monitoring Centre's
      scale indicates a probable association with offending drugs.

PMID- 29033489
TI  - Exact and Approximate Statistical Inference for Nonlinear Regression and the
      Estimating Equation Approach.
AB  - The exact density distribution of the nonlinear least squares estimator in the
      one-parameter regression model is derived in closed form and expressed through
      the cumulative distribution function of the standard normal variable. Several
      proposals to generalize this result are discussed. The exact density is extended
      to the estimating equation (EE) approach and the nonlinear regression with an
      arbitrary number of linear parameters and one intrinsically nonlinear parameter.
      For a very special nonlinear regression model, the derived density coincides with
      the distribution of the ratio of two normally distributed random variables
      previously obtained by Fieller (1932), unlike other approximations previously
      suggested by other authors. Approximations to the density of the EE estimators
      are discussed in the multivariate case. Numerical complications associated with
      the nonlinear least squares are illustrated, such as nonexistence and/or multiple
      solutions, as major factors contributing to poor density approximation. The
      nonlinear Markov-Gauss theorem is formulated based on the near exact EE density
      approximation.

PMID- 29033490
TI  - Carbon dioxide emission-intensity in climate projections: Comparing the
      observational record to socio-economic scenarios.
AB  - The wide spread of projected temperature changes in climate projections does not
      predominately originate from uncertainty across climate models; instead it is the
      broad range of different global socio-economic scenarios and the implied energy
      production that results in high uncertainty about future climate change. It is
      therefore important to assess the observational tracking of these scenarios. Here
      we compare these socio-economic scenarios created in both 1992 and 2000 against
      the recent observational record to investigate the coupling of economic growth
      and fossil-fuel CO2 emissions. We find that global emission intensity (fossil
      fuel CO2 emissions per GDP) rose in the first part of the 21st century despite
      all major climate projections foreseeing a decline. Proposing a method to
      disaggregate differences between scenarios and observations in global growth
      rates to country-by-country contributions, we find that the relative discrepancy
      was driven by unanticipated GDP growth in Asia and Eastern Europe, in particular
      in Russia and China. The growth of emission intensity over the 2000s highlights
      the relevance of unforeseen local shifts in projections on a global scale.

PMID- 29033492
TI  - OPTIMAL DESIGNS FOR SPLINE WAVELET REGRESSION MODELS.
AB  - In this article we investigate the optimal design problem for some wavelet
      regression models. Wavelets are very flexible in modeling complex relations, and
      optimal designs are appealing as a means of increasing the experimental
      precision. In contrast to the designs for the Haar wavelet regression model
      (Herzberg and Traves 1994; Oyet and Wiens 2000), the I-optimal designs we
      construct are different from the D-optimal designs. We also obtain c-optimal
      designs. Optimal (D- and I-) quadratic spline wavelet designs are constructed,
      both analytically and numerically. A case study shows that a significant saving
      of resources may be realized by employing an optimal design. We also construct
      model robust designs, to address response misspecification arising from fitting
      an incomplete set of wavelets.

PMID- 29033491
TI  - The Association of Attitudes about Contraceptives with Contraceptive Use in a
      Random Sample of Colorado Women.
AB  - CONTEXT: Research regarding unintended pregnancy often focuses on how women make
      decisions about whether or not to use contraceptives, and structural barriers to
      contraception. Less research examines how multidimensional attitudinal
      characteristics may be associated with effective contraceptive use. METHODS: In
      fall 2007, we conducted a random telephone survey of 801 sexually active women in
      Colorado to assess associations of the attitudinal dimensions of Planning,
      Partner Communication, and Stigma and Misinformation with contraceptive use. We
      also examine demographic differences on hypothesized predictors. RESULTS: Stigma
      and Misinformation is higher in Latina women, women on Medicaid or with no
      insurance, women with less than a college degree, and women living in small towns
      or rural areas. Partner Communication attitudes are most positive among those
      with a bachelor's degree, and those with less than a high school degree, while
      they are most negative among those living in small towns and rural areas. In
      multivariate analysis, planning to use contraceptives is associated with greater
      likelihood of more effective contraceptive use. Higher levels of planning and
      partner communication are associated with greater likelihood of any contraceptive
      use. DISCUSSION: In addition to addressing structural barriers to contraception,
      interventions to address the need to plan for contraception are vital to mitigate
      the high prevalence of unintended pregnancies in the United States.

PMID- 29033493
TI  - Person-Centeredness in Home- and Community-Based Services and Supports: Domains,
      Attributes, and Assisted Living Indicators.
AB  - As a result of the Centers for Medicare & Medicaid Services (CMS) interest in
      creating a unifying definition of "community living" for its Medicaid Home and
      Community Based Services and Support (HCBS) programs, it needed clarifying
      descriptors of person-centered (PC) practices in assisted living to distinguish
      them from institutional ones. Additionally, CMS's proposed language defining
      "community living" had the unintended potential to exclude many assisted living
      communities and disadvantage residents who receive Medicaid. This manuscript
      describes the consensus process through which clarifying language for "community
      living" and a framework for HCBS PC domains, attributes, and indicators specific
      to assisted living were developed. It examines the validity of those domains
      based on literature review, surveys, and stakeholder focus groups, and identifies
      nine domains and 43 indicators that provide a foundation for defining and
      measuring PC practice in assisted living. Ongoing efforts using community-based
      participatory research methods are further refining and testing PC indicators for
      assisted living to advance knowledge, operational policies, practices, and
      quality outcomes.

PMID- 29033494
TI  - Family Closeness and Domestic Abuse Among Caribbean and South American Women in
      South Florida.
AB  - This paper focuses on the importance of family member closeness as a protective
      factor against domestic abuse. We explore the link between long-lasting relations
      within the family and intra-familial violence perpetrated against women in Latino
      households in South Florida. We use data from an Inter-generational Transmission
      of Drug Use between Latina Mothers and Daughters (ITDMD) study. The study
      includes data on family relations and domestic abuse. We estimate a series of
      multivariate regressions to obtain the probability of abuse against women, the
      types of abuse inflicted and the relationship with the abusers. Our results
      indicate that among abused women, the effects of long-lasting relations within
      the family differ depending on the type of relationship between the abuser and
      the victim and the degree of closeness the victim feels towards other family
      members. Given these findings, there is a need to further study family relations
      and abuse in Latino households.

PMID- 29033495
TI  - Age of First Arrest, Sex, and Drug Use as Correlates of Adult Risk Behaviors
      Among Rural Women in Jails.
AB  - Incarcerated women frequently report initiation of substance use and sexual
      encounters at an early age, and often engage in high-risk drug use and sexual
      behaviors as adults. This study examined the timing of first sex, drug use, and
      arrest, as well as their unique influences on specific risky behaviors in
      adulthood, among a high-risk population of rural women recruited from jails. Ages
      of initiation were all positively and significantly correlated, and each
      independently increased the likelihood of several risky behaviors in adulthood.
      Implications are discussed for screening, intervention, and treatment targeting
      high-risk women and girls in rural areas, particularly within criminal justice
      settings.

PMID- 29033497
TI  - Investigation into the ring-substituted polyanilines and their application for
      the detection and adsorption of sulfur dioxide.
AB  - It has been demonstrated in this study that the substituents on the monomer
      aniline benzene ring are able to introduce the significant differences to the
      resulting polyaniline's collective properties. We systematically evaluated the
      structural perturbation effects of two substituents (methyl and methoxy) of
      aniline monomer through the electrochemical method. Our results showed that the
      methoxy group induces the less structural perturbation than the methyl
      counterpart, because of its partial double bond restriction. The morphologies are
      different for the polyaniline and the ring-substituted polyanilines, in which
      substituted polyanilines feature the larger porosities with the addition of these
      side groups. The influential effects of the methoxy side group have been further
      illustrated and amplified by its superior sensing performance towards the
      environmentally-significant sulfur dioxide gas, evaluated through the
      construction of the quartz crystal microbalance (QCM)-based gas sensor with these
      polyaniline materials. The as-constructed gas sensor's sensitivity, selectivity
      and stability in terms of its SO2 responses have been evaluated in details. The
      methoxy-substituted polyaniline was tested to show the unique gas sensing
      properties for the sulfur dioxide at the low concentrations (50-250 ppm) and
      function as the adsorbing material at the high concentrations (500-1250 ppm).
      Thus it can be used both as sensing material as well as a novel filter and/or
      storage reservoir for the removal of sulfur dioxide pollutant from the
      environments.

PMID- 29033496
TI  - Colloidal CuFeS2 Nanocrystals: Intermediate Fe d-Band Leads to High Photothermal
      Conversion Efficiency.
AB  - We describe the colloidal hot-injection synthesis of phase-pure nanocrystals
      (NCs) of a highly abundant mineral, chalcopyrite (CuFeS2). Absorption bands
      centered at around 480 and 950 nm, spanning almost the entire visible and near
      infrared regions, encompass their optical extinction characteristics. These peaks
      are ascribable to electronic transitions from the valence band (VB) to the empty
      intermediate band (IB), located in the fundamental gap and mainly composed of Fe
      3d orbitals. Laser-irradiation (at 808 nm) of an aqueous suspension of CuFeS2 NCs
      exhibited significant heating, with a photothermal conversion efficiency of 49%.
      Such efficient heating is ascribable to the carrier relaxation within the broad
      IB band (owing to the indirect VB-IB gap), as corroborated by transient
      absorption measurements. The intense absorption and high photothermal
      transduction efficiency (PTE) of these NCs in the so-called biological window
      (650-900 nm) make them suitable for photothermal therapy as demonstrated by tumor
      cell annihilation upon laser irradiation. The otherwise harmless nature of these
      NCs in dark conditions was confirmed by in vitro toxicity tests on two different
      cell lines. The presence of the deep Fe levels constituting the IB is the origin
      of such enhanced PTE, which can be used to design other high performing NC
      photothermal agents.

PMID- 29033498
TI  - A new proof of geometric convergence for the adaptive generalized weighted analog
      sampling (GWAS) method.
AB  - Generalized Weighted Analog Sampling is a variance-reducing method for solving
      radiative transport problems that makes use of a biased (though asymptotically
      unbiased) estimator. The introduction of bias provides a mechanism for combining
      the best features of unbiased estimators while avoiding their limitations. In
      this paper we present a new proof that adaptive GWAS estimation based on
      combining the variance-reducing power of importance sampling with the sampling
      simplicity of correlated sampling yields geometrically convergent estimates of
      radiative transport solutions. The new proof establishes a stronger and more
      general theory of geometric convergence for GWAS.

PMID- 29033499
TI  - Fabrication and Characterization of Electrospun Thermoplastic
      Polyurethane/Fibroin Small-Diameter Vascular Grafts for Vascular Tissue
      Engineering.
AB  - The demand for small-diameter blood vessel substitutes has been increasing due to
      a shortage of autograft vessels and problems with thrombosis and intimal
      hyperplasia with synthetic grafts. In this study, hybrid small-diameter vascular
      grafts made of thermoplastic polyurethane (TPU) and silk fibroin, which possessed
      a hybrid fibrous structure of an aligned inner layer and a random outer layer,
      were fabricated by the electrospinning technique using a customized striated
      collector that generated both aligned and random fibers simultaneously. A
      methanol post-treatment process induced the transition of fibroin protein
      conformation from the water-soluble, amorphous, and less ordered structures to
      the water-insoluble beta-sheet structures that possessed robust mechanical
      properties and relatively slow proteolytic degradation. The methanol post
      treatment also created crimped fibers that mimicked the wavy structure of
      collagen fibers in natural blood vessels. Ultrafine nanofibers and nanowebs were
      found on the electrospun TPU/fibroin samples, which effectively increased the
      surface area for cell adhesion and migration. Cyclic circumferential tensile test
      results showed compatible mechanical properties for grafts made of a soft
      TPU/fibroin blend compared to human coronary arteries. In addition, cell culture
      tests with endothelial cells after 6 and 60 days of culture exhibited high cell
      viability and good biocompatibility of TPU/fibroin grafts, suggesting the
      potential of applying electrospun TPU/fibroin grafts in vascular tissue
      engineering.

PMID- 29033500
TI  - Synthesis of 3,3'-Disubstituted Indolenines Utilizing the Lewis Acid Catalyzed
      Alkylation of 2,3-Disubstituted Indoles with Trichloroacetimidates.
AB  - Trichloroacetimidates function as effective electrophiles for the selective C3
      alkylation of 2,3-disubstituted indoles to provide 3,3'-disubstituted
      indolenines. These indolenines are common synthetic intermediates that are often
      utilized in the synthesis of complex molecules. Effective reaction conditions
      utilizing Lewis acid catalysts have been determined, and the scope of the
      reaction with respect to indole and imidate reaction partner has been
      investigated. This chemistry provides an alternative to base promoted and
      transition metal catalyzed methods that are more commonly utilized to access
      similar indolenines.

PMID- 29033501
TI  - Eight-Channel Monopole Array Using ICE Decoupling for Human Head MR Imaging at 7
      T.
AB  - Due to the unique structure of radiative coil elements, traditional decoupling
      methods face technical challenges in reducing the electromagnetic coupling of the
      radiative arrays. In this study, we aim to investigate the possibility of using
      the recently introduced induced current elimination (ICE) decoupling technique
      for cylindrical shaped radiative coil array designs. To evaluate the method, an
      eight-channel transmit/receive monopole array with the ICE decoupling, suitable
      for human head imaging at 7 T, was built and comparatively investigated. In vivo
      human head images were acquired and geometry factor maps were measured and
      calculated to evaluate the performance of the ICE-decoupled monopole array.
      Compared with the monopole array without decoupling methods, the ICE-decoupled
      monopole array had a higher signal-to-noise ratio and demonstrated improved
      parallel imaging ability. The experimental results indicate that the ICE
      decoupling method is a promising solution to addressing the coupling issue of
      radiative array at ultrahigh fields.

PMID- 29033502
TI  - Biomechanical model based evaluation of Total Hip Arthroplasty therapy outcome.
AB  - OBJECTIVE: Total-hip-arthroplasties are performed to treat patients with
      osteoarthritis. Surgical planning is usually based on specific radiographs. These
      information could also be used as data for biomechanical modelling. METHODS:
      Models are rarely used during clinical practice. Our aim was to analyze model
      based the pre- and postoperatively hip-biomechanic. Pre- and postoperative X-rays
      of 30 patients were examined by using 4 biomechanical-models. RESULTS: The
      received results showed variations e.g. an increase and decrease of hip-load pre-
      and postoperative. CONCLUSION: With the data of these models it would be possible
      to integrate the amplitude and orientation of the hip-joint-resultant-force into
      the therapeutical approach.

PMID- 29033503
TI  - The Management and Prognostic Factors of Acute Coronary Syndrome: Evidence from
      the Taiwan Acute Coronary Syndrome Full Spectrum Registry.
AB  - Cardiovascular disease (CVD) accounts for approximately one-third of all global
      deaths, and acute coronary syndrome (ACS) is the most severe form of CVD. It is
      of notable importance to develop ACS strategies for reducing major adverse
      cardiac events (MACE) and preventing complications. In the Taiwan ACS Full
      Spectrum Registry, 1-year mortality among patients with ST-segment elevation
      myocardial infarction, non ST-segment elevation myocardial infarction and
      unstable angina was 6.1%, 10.1%, and 6.2%, respectively. ACS patients with
      diabetes had significantly worse outcomes in terms of all-cause death and MACE
      compared to those without diabetes. In-hospital bleeding or chronic kidney
      disease (CKD) was independently associated with MACE, and ACS patients with both
      bleeding and CKD had the worst outcome. Use of clopidogrel in conjunction with an
      invasive strategy could decrease mortality and improve outcomes in the CKD
      population. CHADS2 and CHA2DS2-VASc scores were useful predictors of subsequent
      MACE, and renal dysfunction could further improve the prognostic impact of the
      CHA2DS2-VASc score. For high-risk patients with non-ST-elevation acute coronary
      syndrome (NSTE-ACS), percutaneous coronary intervention (PCI) within 24-72 hours
      from symptom onset was demonstrably the optimal time. Suboptimal secondary
      preventive therapy demonstrated a need for further improvement. The ACS Full
      Spectrum Registry provided an in-depth analysis of ACS management in Taiwan.

PMID- 29033505
TI  - Transcatheter Aortic Valve Implantation in Taiwan: Still Evolving!

PMID- 29033504
TI  - Procedural Characteristics and Outcomes of Transcatheter Aortic Valve
      Implantation: A Single-Center Experience of the First 100 Inoperable or High
      Surgical Risk Patients with Severe Aortic Stenosis.
AB  - BACKGROUND: This is the first study of a Taiwanese population reporting
      transcatheter aortic valve implantation (TAVI) outcomes of the first 100 cases
      from a single center offering two different transcatheter heart valve
      technologies via six types of approaches. We herein report the 30-day and one
      year outcomes in our first 100 TAVI patients at Taipei Veterans General Hospital.
      METHODS: From May 2010 to April 2016, 100 consecutive patients with severe aortic
      stenosis (AS) who were considered unsuitable or at high risk for surgical aortic
      valve replacement underwent TAVI. Patient outcomes were classified according to
      the Valve Academic Research Consortium-2 (VARC-2) definitions. The device
      performance was assessed using transthoracic echocardiography by independent
      investigators. RESULTS: The mean patient age was 81.1 years, where 54% were
      female, and the mean Logistic EuroSCORE was 21.5%. The Medtronic CoreValve was
      used in 84 patients and the Edwards Sapien or Sapien XT valve (ESV) in 16. The
      transfemoral approach was the most frequently used route (83%), followed by
      transapical (9%) access. Overall, there was no procedural death. The VARC-2
      outcomes were as follows: device success, 95%; stroke, 1%; major vascular
      complication, 3%; a need for pacemaker implantation, 5.1%. At discharge, the
      incidence of postoperative mild, moderate or severe paravalvular leak was 30%, 3%
      and 0%, respectively. At one year, the all-cause mortality rate was 14.0%, and no
      valve-related dysfunction was observed. Through multivariable analysis, non
      transfemoral access [hazard ratios (HR) 4.81; 95% confidence interval (CI) 1.66
      14.09; p = 0.004] and advanced chronic kidney disease (stages 4-5), (HR 3.13; 95%
      CI 1.07-9.09; p = 0.036) were independently associated with an increased risk of
      one-year mortality. CONCLUSIONS: We demonstrated that TAVI shows good early and
      mid-term outcomes in terms of survival, technical success, valve-related adverse
      events and haemodynamic performance in high-risk patients with severe AS.

PMID- 29033506
TI  - The Impact of Fractional Flow Reserve-Guided Coronary Revascularization in
      Patients with Coronary Stenoses of Intermediate Severity.
AB  - BACKGROUND: Previous studies have shown that the use of fractional flow reserve
      (FFR) in addition to angiography significantly reduced the rate of all major
      adverse cardiovascular events (MACE). However, this practice has not been widely
      accepted and limited outcome data exist about FFR-guided percutaneous coronary
      intervention (PCI) in Taiwan. The aim of the present study was to evaluate the
      possible impact of FFR-guided PCI in coronary stenoses of intermediate severity.
      METHODS: We performed a retrospective case-control study on 443 cases of
      intermediate coronary stenoses in 206 patients recruited from our computerized
      database. The study patients were divided into two groups: the FFR group (n =
      101) and the angiography group (n = 105), matched with age, gender, clinical and
      angiographic lesion characteristics. In the angiography group, the indicated
      lesions had been treated with PCI by angiographic or anatomical assessment,
      whereas those patients in the FFR group underwent PCI of indicated lesions only
      if the FFR was < 0.80. The primary end point was the MACE rate regarding death,
      nonfatal myocardial infarction (MI), and target vessel failure at a mean follow
      up of 418 days. RESULTS: The MACE rate was similar in both groups (6% in the
      angiography group and 3% in the FFR group, p = 0.06). However, FFR-guided PCI
      strategy prevented unnecessary revascularization in up to 75% of patients, and
      markedly reduced costs of the index hospitalization. Moreover, multivariate
      analysis found that the use of drug-eluting stent and statin therapy, and the
      presence of family history of premature coronary artery disease and
      periprocedural MI are independent predictors of clinical outcomes. CONCLUSIONS:
      FFR-guided intervention, compared to angiography-guided intervention for
      Taiwanese patients with coronary stenoses of intermediate severity, achieved
      similar clinical outcomes and provided cost-savings.

PMID- 29033507
TI  - SYNTAX Score of Infarct-Related Artery Other Than the Number of Coronary Balloon
      Inflations and Deflations as an Independent Predictor of Contrast-Induced Acute
      Kidney Injury in Patients with ST-Segment Elevation Myocardial Infarction.
AB  - BACKGROUND: Although remote ischemic post-conditioning (RIPC) has been shown to
      prevent contrast-induced acute kidney injury (CIAKI) in patients with acute
      coronary syndrome, its efficacy in patients with ST-segment elevation myocardial
      infarction (STEMI) remains unclear. We examined the relationship among balloon
      inflations and deflations (BID) times, SYNTAX score of infarction-related artery
      (SI), periprocedural complications, and CIAKI in STEMI patients undergoing
      primary percutaneous coronary intervention (pPCI). METHODS: Patients with STEMI
      undergoing pPCI with Mehran risk score (MRS) >= 5 were enrolled between February
      2007 and September 2012. The study end point was the development of CIAKI.
      RESULTS: Of 206 patients, the median age was 65 years [interquartile range (IQR):
      55-77] with 72.8% male and Mehran risk score (MRS) 8 (IQR: 6-12). Receiver
      operating characteristic curve showed that BID times > 9 times or SI > 10 was the
      best cut-off associated with CIAKI. In univariate analysis, significant
      association with CIAKI existed in BID > 9 times [odds ratio (OR): 3.106, 95%
      confidence interval (CI): 1.284-7.513, p = 0.012] and SI > 10 (OR: 3.909, 95% CI:
      1.570-9.735, p = 0.003). Other variables associated with CIAKI included
      creatinine, hemoglobin, angiotensin converting enzyme inhibitor or angiotensin
      receptor blocker use at discharge. In multivariate analysis, SI > 10 remained an
      independent predictor of CIAKI in different adjustment model, even on top of MRS
      (adjusted OR: 3.498, 95% CI: 1.086-11.268, p = 0.036). CONCLUSIONS: Vascular
      complexity of infarct-related artery rather than higher BID times (> 9) was the
      major determinant of the development of CIAKI after pPCI in STEMI patients.

PMID- 29033508
TI  - Predictors of Mortality in Elderly Patients with Non-ST Elevation Acute Coronary
      Syndrome - Data from Taiwan Acute Coronary Syndrome Full Spectrum Registry.
AB  - BACKGROUND: Some difficulties and variations remain associated with the care of
      elderly patients with non-ST elevation acute coronary syndrome (NSTE-ACS).
      METHODS: We included 1470 patients from a Taiwan nationwide registry who
      fulfilled the criteria of NSTE-ACS, and stratified these patients by age and
      evaluated the treatment, complications and outcomes in different age groups.
      Furthermore, we analyzed risk factors and standards of care to determine the
      predictors of mortality. RESULTS: Patients >= 75 years of age (n = 396) had
      significantly higher incidences of 90-day mortality [odd ratio (OR) = 4.5 (1.2
      16.3), p = 0.023] and 1-year mortality [OR = 4.9 (2.0-12.3), p = 0.001] compared
      with those patients 45-64 years of age (n = 595). In the patients >= 75 years of
      age, previous myocardial infarction (MI) [OR = 3.3 (1.1-9.8), p = 0.035], statins
      [OR = 0.35 (0.1-0.9), p = 0.037], left ventricular ejection fraction (LVEF) < 35%
      [OR = 3.9 (1.5-10.4), p = 0.006] were associated with 90-day mortality.
      Furthermore, previous MI [OR = 4.0 (1.3-12.6), p = 0.019] was an independent
      predictor of 90-day mortality. Age [OR = 1.1 (1.03-1.2), p = 0.002], previous MI
      [OR = 2.2 (1.1-4.4), p = 0.034], angiotensin-converting enzyme inhibitor or
      angiotensin receptor blocker [OR = 0.5 (0.3-0.9), p = 0.028], and LVEF < 35% [OR
      = 4.3 (1.9-9.5), p < 0.001] were associated with 1-year mortality. Furthermore,
      previous MI [OR = 2.6 (1.1-6.5), p = 0.037], LVEF < 35% [OR = 4.7 (1.5-14.4), p =
      0.007] and percutaneous coronary intervention(PCI) or not [OR = 0.3 (0.1-0.9), p
      = 0.021] were independent predictors of 1-year mortality. CONCLUSIONS: Previous
      MI, LVEF < 35% and PCI or not could predict 1-year mortality in advanced elderly
      patients with NSTE-ACS. Despite their elevated morbidities and complications, PCI
      was still beneficial for these patients.

PMID- 29033509
TI  - Predictors of Impaired Reperfusion after Percutaneous Coronary Intervention in
      Patients with In-Hospital Acute Stent Thrombosis: A Retrospective Analyses of 5
      Years of Data.
AB  - BACKGROUND: Acute stent thrombosis (STh) is a rare complication of percutaneous
      coronary intervention (PCI) and is associated with a high-risk of reperfusion
      failure. However, data focusing on risk factors of reperfusion failure in
      patients undergoing repeat PCI for treatment of STh remains inadequate. METHODS:
      A total of 8815 patients who underwent PCI with stent implantation from January
      2009 to December 2013 were retrospectively reviewed. Among those cases, patients
      that presented with acute STh and underwent a repeat PCI for acute STh were
      identified. RESULTS: There were 108 patients who underwent repeat PCI for the
      treatment of in-hospital acute STh that were retrospectively analyzed. Of these
      study subjects, 21 (25%) had thrombolysis in myocardial infarction (TIMI) flow <
      3 after repeat PCI. The median value of pain-to-balloon time was 40 minutes in
      the TIMI < 3 group, 35 minutes in the TIMI = 3 group (p < 0.001), and the first
      PCI-to-stent thrombosis time was also longer in the TIMI < 3 group (10 hours vs.
      2.5 hours, p = 0.001). When patients were evaluated according to PCI time, the
      percentage of patients with TIMI < 3 was significantly higher in the night period
      compared to the daytime period (46.4% vs. 17.5 %, p = 0.002). In the
      multivariable logistic regression analysis, stent length [odds ratio (OR) = 1.18,
      95% confidence interval (CI) 1.008-1.38] and pain-to- balloon time (OR = 1.28,
      95% CI, 1.06-1.54) were the only independent predictors of failed reperfusion.
      CONCLUSIONS: Baseline stent length and pain-to-balloon time were associated with
      reperfusion failure in PCI for STh. Moreover, TIMI flow grade showed a circadian
      variation.

PMID- 29033510
TI  - Admission Value of Serum Cathepsin D Level Can be Useful for Predicting In
      Hospital Mortality in Patients with NSTEMI.
AB  - BACKGROUND: We aimed to investigate the association of serum cathepsin D levels
      with in-hospital mortality and Syntax scores (SXscore) in non-ST elevation
      myocardial infarction (NSTEMI) patients. METHODS: A total of 88 patients were
      included in the study. The patients were divided into two groups: those with in
      hospital mortality (-), and those with in-hospital mortality (+). The receiver
      operating characteristics curve was used to show the sensitivity and specificity
      of serum cathepsin D levels, and the optimal cut-off value for predicting in
      hospital mortality and high SXscore. RESULTS: Patients with (+) in-hospital
      mortality and high SXscore had lower serum cathepsin D levels compared to the
      patients with (-) in-hospital mortality and low SXscore. Using a cutoff score of
      < 16 for the cathepsin D level, in-hospital mortality was predicted with a
      sensitivity and specificity of 73.4% and 77.6%, respectively, and also predicted
      high SXscore with a sensitivity and specificity of 72.4% and 67.6%, respectively.
      CONCLUSIONS: Serum cathepsin D levels established upon admission were
      significantly and independently lower in NSTEMI patients with high rate of
      mortality, high SXscores, and low left ventricular ejection fraction.

PMID- 29033511
TI  - Changes of Atrial Natriuretic Peptides after Defibrillation Threshold Testing
      Predicted Future Ventricular Arrhythmia Event.
AB  - BACKGROUND: We investigated the change of natriuretic peptides during
      defibrillation threshold (DFT) testing and its relationship with future
      ventricular arrhythmia (VA) events in patients implanted with an implantable
      cardioverter defibrillator (ICD). METHODS: Atrial natriuretic peptide (ANP),
      brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP) were
      measured in 21 patients (mean age 61 +/- 13 years; 67% male) undergoing ICD
      implantation. Blood samples of the patients were drawn at pre-implantation, 30
      minutes, 60 minutes, and 24 hours after DFT testing. The patients were followed
      and divided into two groups according to the occurrence of VA in 18 months. The
      biomarker levels and their changes were compared in patients with and without
      further VA. RESULTS: The pre-implantation ANP levels were higher at pre
      implantation and increased significantly at 30 minutes after DFT testing
      (Delta30minANP) among patients with VA events. The BNP and CNP levels did not
      change significantly after DFT testing in both groups. The area under curve was
      0.82 for the change in Delta30minANP determining further ventricular events. The
      optimal Delta30minANP cutoff value was 0.51 pg/ml, with sensitivity of 0.83 and
      specificity of 0.68. Multivariable analysis confirmed that patients with
      Delta30minANP more than 0.51 pg/ml have a higher risk of further ventricular
      events (hazard ratio 39.8, 95% confidence interval: 2.87-553.01, p = 0.006). The
      pre-implantation ANP level could not predict future VA events (hazard ratio 1.06,
      95% CI: 1.00-1.14, p = 0.06). CONCLUSIONS: The increase of ANP concentration
      after DFT testing predicted future VA events after ICD implantation while the BNP
      and CNP levels did not predict future VA events.

PMID- 29033512
TI  - Heart Rate Recovery as a Novel Test for Predicting Cardiac Involvement in Beta
      Thalassemia Major.
AB  - BACKGROUND: Abnormal heart rate recovery (HRR) is predictive of cardiac
      mortality. Autonomic abnormalities in beta-thalassemia major (TM) patients have
      been reported in previous studies. However, the importance of low HRR in exercise
      stress test in TM patients has not yet been ascertained. Therefore, this study
      will be the first of its kind in the literature. METHODS: Exercise stress test
      was performed on 56 TM patients who were being treated at the Thalassemia Center
      of our hospital, along with 46 non-TM iron deficiency anemia (IDA) patients as a
      control group. Values for HHR were recorded at 1, 2, 3, 4 and 5 min, and HRR was
      calculated by the difference of heart rate at peak exercise and at a specific
      time interval following the onset of recovery. RESULTS: All HRR values were found
      to be lower in TM patients compared to those in the IDA group. Exercise capacity
      [metabolic equivalents (METs)] was also found to be low in these patients (p <
      0.001) as well. Total exercise time was significantly lower in the TM group
      compared to the IDA group (8.40 +/- 1.7 min vs. 11.17 +/- 1.51 min, p < 0.001).
      Exercise capacity (METs) was also lower in the TM group compared to the IDA
      group. Mean T2* value was 28.3 +/- 13.7 ms in TM patients on magnetic resonance
      imaging (MRI). In addition, there are 18 TM patients with T2* value was < 20 ms.
      CONCLUSIONS: This study found that TM was independently associated with low HRR.
      Such a condition is an indicator of autonomic dysfunction in TM patients, since
      abnormal HRR is related to impaired autonomic response. In addition, impaired HRR
      may be a marker of early cardiac involvement in patients, whose T2* value is high
      on MRI. Modifying HRR with a cardiac rehabilitation program in TM patients with
      impaired HRR is a field open for further investigation.

PMID- 29033513
TI  - The Endothelial Nitric Oxide Synthase (NOS3-786T>C) Genetic Polymorphism in
      Chronic Heart Failure: Effects of Mutant -786C allele on Long-term Mortality.
AB  - BACKGROUND: Nitric oxide plays an important role in the regulation of basal
      vascular tone and cardiac myocyte function. We investigated the NOS3-786T>C
      polymorphism in chronic heart failure (CHF) and its effects on long-term
      mortality. METHODS: Ninety-one patients with CHF who were referred to the
      Department of Cardiology of Siyami Ersek Cardiovascular and Thoracic Surgery
      Center for cardiopulmonary exercise testing between April 2001 and January 2004
      and 30 controls were enrolled in this study. Patient were followed prospectively
      for a period of 1 to 12 years. RESULTS: Patients and controls were divided into
      three groups: TT, TC and CC, according to their NOS3-786T>C polymorphism. We
      noted that there was no significant difference in the genotype distribution
      between patients and controls. There was also no significant difference in
      endothelial nitric oxide synthase (eNOS) gene polymorphism between ischemic HF
      and nonischemic HF. During the follow-up period, 61 (67%) deaths occurred. The
      nonsurvivor group had lower left ventricular ejection fraction (LVEF) (p = 0.01),
      reduced peak oxygen consumption (p = 0.04) and were of older age (p = 0.001).
      Age, LVEF, peak oxygen consumption and genotype were found to be predictors of
      mortality (p < 0.05). Additionally, mortality was significantly increased in 
      786CC genotype patients compared to TT genotype patients (hazard ratio = 2.2; p =
      0.03). By multivariate analysis, age and eNOS genotype were determined to be
      significant independent predictors of death. Additionally, Kaplan-Meier analysis
      confirmed that homozygote -786C genotype was associated with an increased risk of
      death (chi2 = 4.6, p = 0.03). CONCLUSIONS: Our findings showed that the NOS3
      786T>C polymorphism was associated with an increased risk of mortality in
      patients with CHF.

PMID- 29033514
TI  - The Association between CHA2DS2-VASc Score and Mortality in Patients with Heart
      Failure with Reduced Ejection Fraction.
AB  - BACKGROUND: Heart failure (HF) is associated with significant mortality and
      morbidity. Therefore, identifying high-risk patients may optimize treatment for
      HF patients and reduce adverse events. The aim of this study was to assess the
      role of the CHA2DS2-VASc score to predict mortality in patients with reduced left
      ventricular ejection fraction (LVEF). METHODS: A total of 106 patients with
      reduced LVEF were enrolled in this study. All patients completed a one-year
      follow-up, and a CHA2DS2-VASc score was calculated for each patient. RESULTS:
      Twenty-one patients (19.8%) died during the 1-year follow-up. We found that
      baseline functional status, CHA2DS2-VASc score, brain natriuretic peptide, blood
      urea and hemoglobin levels were associated with mortality. In the multivariate
      analysis, CHA2DS2-VASc score and functional capacity were the only predictors of
      1-year mortality. CONCLUSIONS: Use of the CHA2DS2-VASc score appears to be
      feasible for risk stratification and mortality prediction in patients with
      reduced LVEF.

PMID- 29033515
TI  - CHA2DS2-VASc Score: A Simple But Not Appropriate Risk Score for Predicting
      Mortality Risk in Patients with Heart Failure.

PMID- 29033516
TI  - Primary Endovascular Intervention for Acute Mesenteric Ischemia Performed by
      Interventional Cardiologists - A Single Center Experience.
AB  - The current standard care for acute mesenteric ischemia (AMEI) involves urgent
      revascularization and resection of the necrotic bowel. Since 2012, we have used
      an AMEI protocol of our own design, which focused on early treatment and allowed
      interventional cardiologists to become involved when interventional radiologist
      was not available. A total of 8 patients were treated, and two interventional
      cardiologists performed all the stenting procedures. The procedure success rate
      was 100% in patients with non-calcified lesions (6/8). The 30-day survival rate
      was 100% in patients with angiographic success, and was 0% in patients with
      failed procedure. In two patients with total occlusion of the superior mesenteric
      artery, laparotomy was avoided when interventions were successful and completed
      within six hours of protocol activation. Four surviving patients were discharged
      after short intensive care unit stays (less than 48 hours); these patients
      returned to and remained at home throughout their 90-day follow-up. The overall
      procedure success rate and 30-day survival rate were both 75%. There was no
      access site or intervention-related complications. Using our protocol, we believe
      that primary endovascular treatment for AMEI is feasible. In geographic regions
      where healthcare resources are lacking, a time-efficient strategy adopted by
      interventional cardiologists should be considered for the purpose of saving lives
      and possibly even avoiding open laparotomy.

PMID- 29033517
TI  - ALCAPA Syndrome and Atrial Septal Defect In a 68-Year-Old Woman: An Extremely
      Rare Congenital Association.
AB  - Anomalous left coronary artery arising from the pulmonary artery (ALCAPA) has
      been generally reported as an isolated lesion that is also called Bland-White
      Garland syndrome. Herein we report a case of ALCAPA syndrome with an atrial
      septal defect in a 68-year-old woman. She had been asymptomatic until the age of
      68. Echocardiographic examination revealed atrial septal defect, and coronary
      angiography showed that the left main coronary artery originated from the
      pulmonary artery and intensive collateral connections between the right and left
      coronary artery. In this case, it would appear that ALCAPA is associated with
      atrial septal defect.

PMID- 29033518
TI  - A Rare Experience of Infective Residual Sheath in the Wall of the Innominate Vein
      after Extraction of Implantable-Defibrillators.
AB  - BACKGROUND: Cardiac device-related infective endocarditis is an uncommon but
      potentially fatal complication. Therefore, cardiac devices should be removed as
      soon as a device-related infection is suspected. CASE REPORT: A 56-year-old male
      with a history of arrhythmogenic right ventricular dysplasia with implantable
      cardioverter-defibrillators (ICDs) 7 years earlier and re-implantation of ICDs
      due to dysfunction 18 months ago presented with erosion of the ICD pocket with
      Pseudomonas bacteremia. For the past year, only multiple wound debridements were
      performed. Accordingly, we performed debridement and removal of the generator
      during this admission; however, bacteremia still persisted. Using transesophageal
      echocardiography, we detected vegetation on the pacing leads and tricuspid valve
      in the right atrium. We performed thoracotomy with tricuspid valve repair and
      pacing wire removal. However, anterior chest pain and refractory bacteremia
      occurred 3 months later after discharge, and an infectious foreign body in the
      wall of the innominate vein was detected using chest computer tomography.
      Thoracotomy was again performed for resection of the innominate vein with the
      infection source. Postoperative recovery was good, with no systemic infection or
      bacteremia. CONCLUSIONS: Pacing lead extraction is a common procedure following
      cardiac rhythm management device-related infection. However, residual foreign
      body-related bacteremia should be suspected in cases with fever of unknown origin
      after primary surgery. Preserving the innominate vein with patch repair is a
      feasible option. However, a postoperative 4-week course of antibiotics is
      recommended.

PMID- 29033519
TI  - End-QRS Notching and Slurring in the Definition of Early Repolarization.

PMID- 29033520
TI  - Author Reply to Letter to the Editor: Silent and Malignant Early Repolarization
      Syndrome Mimicking Hyper-Acute ST Elevation Myocardial Infarction.

PMID- 29033521
TI  - Reliability of rubrics in the assessment of orthodontic oral presentation.
AB  - AIMS: The aim of this study was to evaluate the reliability of using rubrics in
      dental education, specifically for undergraduate students' assessment in
      orthodontic oral presentation. METHODS: A rubric-based case presentation
      assessment form was introduced to three contributing instructors. In each
      instructor's group, the course director, along with the assigned instructor,
      assessed 8 randomly selected fourth year male dental students utilizing the same
      assessment form (total of 24 students). The two final scorings made by the
      assigned instructor and the course director were then gathered for each student.
      The data of this prospective comparative study then was analyzed using paired t
      test to look for any significant differences in the scoring of the course
      director and each instructor in each group. RESULTS: No significant statistical
      differences were detected in grading variables between the instructors and the
      course director. Furthermore, the data showed no significant correlations between
      the students' final course grade, and their case presentation grades scored by
      instructors'/course director. CONCLUSION: Despite the elaborate nature of the
      routine orthodontic case presentation, the use of rubrics was found to be a
      promising reliable assessment element.

PMID- 29033523
TI  - Mothers' teething beliefs and treatment practices in Mansoura, Egypt.
AB  - OBJECTIVES: To reveal mothers' beliefs about signs and symptoms associated with
      teething and their treatment practices. POPULATION AND METHODS: A cross-sectional
      study done in Mansoura District on 457 mothers and their children with one or
      more erupted teeth. Mothers were interviewed during vaccination session at 25
      chosen health facilities. Mothers were asked whether they agree or disagree about
      24 signs and symptoms claimed to be associated with teething. RESULTS: Only 1.8%
      reported no symptoms at the time of teething. Majority had correct knowledge
      related to bite fingers/objects (70.5%) and drooling (60.0%). Inaccurate
      knowledge was reported as gum rubbing (42.0%), gum swelling (47.0%), diarrhea
      (51.0%), fever (83.2%) and weight loss (46.0%). Only 16.8% of mothers have good
      knowledge about teething problems. Logistic regression analysis revealed that the
      independent predictors of good knowledge are higher education (AOR = 3.7), urban
      residence (AOR = 2.5) and having a first-born child (AOR = 5.5). Only 13.4% of
      mothers did not give any treatment for teething problems. Antipyretics and
      antibiotics were the most frequently given treatments (71.3%, and 24.3%;
      respectively). CONCLUSIONS: The majorities of mothers had low knowledge about
      teething problems and gave unnecessary treatments.

PMID- 29033522
TI  - Mandibular alveolar bone volume in patients with different vertical facial
      dimensions.
AB  - OBJECTIVE: To evaluate if there is any difference in alveolar bone surface area
      in patients with high vertical facial dimension (long face), average vertical
      facial dimension (average face), and low vertical facial dimension (square short
      face). MATERIALS AND METHODS: Forty-five patients who had cone beam computed
      tomography (CBCT) as part of their orthodontic records were chosen according to
      their facial vertical dimension. Each group consisted of fifteen patients.
      Mandibular alveolar bone volume was calculated using Dolphin 3D Imaging software
      as the total surface area of the symphysis at the level of lower right canine to
      lower left canine and total surface areas for each patient was considered as
      total bone volume. Comparison was performed between groups using t-test. RESULTS:
      Long face type patients showed higher bone volume (total surface area 3220 +/-
      368 mm2), average face patients have average bone volume (total surface area 2059
      +/- 620 mm2) while square short face patients have the lowest total bone volume
      (total surface area 1877 +/- 112 mm2). There was a significant difference between
      long face and square short face groups (P < 0.005) however, there was no
      significant difference between long face and average face groups. CONCLUSIONS:
      Patients with long face type have higher mandibular alveolar bone volume compared
      to short facial type patients.

PMID- 29033525
TI  - Oral health comprehension in parents of Saudi cerebral palsy children.
AB  - OBJECTIVE: To determine oral health comprehension among parents of cerebral palsy
      (CP) children. METHODS: A self-administered questionnaire was utilized to obtain
      the required information. The study was conducted in two main centers for
      disabled children in Riyadh, Saudi Arabia. RESULTS: Parents of all 157 CP
      children registered in the two centers completed the questionnaire. Mothers
      mostly (86.6%) completed the questionnaire. Majority (98.7%) of the parents knew
      the importance of dental health for general health. More than two-third (70%) of
      the parents thought that teeth should be brushed thrice daily or after each meal.
      About three in every ten (29.9%) parents were not aware of the beneficial effect
      of fluoride in preventing dental caries; and very few (9.6%) were aware of water
      as a source of fluoride. Almost all (98.7%) the parents knew that sugary foods
      caused dental caries. Three-fourth (75.8%) of the parents were not aware of the
      possible harmful effects of bottled juices on teeth. There were no significant (p
      > 0.05) associations between the parental age/gender with any of the dependent
      variables. CONCLUSION: Parents of CP children generally showed satisfactory oral
      health comprehension. However, they need further oral health education in several
      areas.

PMID- 29033524
TI  - Influence of platelet rich fibrin on post-extraction socket healing: A clinical
      and radiographic study.
AB  - AIM: The aim of this study was to evaluate clinically and radiographically,
      extraction socket healing using autologous platelet rich fibrin (PRF). MATERIALS
      AND METHODS: Twenty-four subjects needing single tooth simple extractions were
      selected. Twenty-four extraction sockets were divided into test group (PRF, n =
      12) and control group (blood clot, n = 12). PRF was prepared with blood drawn
      from individuals after extraction using standard technique. PRF was placed in
      test group sockets followed by pressure application and figure 8 sutures. Sockets
      in control group were allowed to heal in the presence of blood clot and received
      a figure 8 suture. Ridge width was assessed using cast analysis with the help of
      acrylic stent and a pair of calipers. Radiographic analysis of socket surface
      area was performed using computer graphic software program. The clinical follow
      up assessments were performed at 1, 4 and 8 weeks. Collected data was assessed
      using ANOVA and multiple comparisons test. RESULTS: Subjects were aged between 25
      and 50 (mean 37.8) years, including 15 females. The mean horizontal ridge width
      for sockets in the test group were 11.70 +/- 2.37 mm, 11.33 +/- 2.30 mm and 10.97
      +/- 2.33 mm at 1, 4 and 8 weeks respectively. Ridge width proportions were
      significantly higher among test group as compared to control group between
      baseline to 4 and 8 weeks respectively. The mean radiographic bone fill (RBF)
      percentage in the test group, was 74.05 +/- 1.66%, 81.54 +/- 3.33% and 88.81 +/-
      1.53% at 1, 4 and 8 weeks respectively. The mean RBF was significantly higher in
      the test group than control group at all time intervals. CONCLUSION: The study
      outcomes demonstrate that the use of PRF accelerate socket wound healing after
      tooth extraction as noticed by increased bone fill and reduced alveolar bone
      width resorption using clinical and radiographic methods.

PMID- 29033526
TI  - Complexity of comprehensive care treatments in undergraduate dental programs: The
      benefits of observing and assisting experienced faculty members.
AB  - OBJECTIVE: To improve the confidence of the final year dental students in
      completing occlusal and oral rehabilitation of patients, with complexities beyond
      their scope, based on full analysis of the biomechanical and esthetic
      considerations of each case. MATERIAL & METHODS: Two comprehensive patient
      situations presenting with special difficulties including extensive, reduced
      vertical dimension of occlusion, limited interocclusal space and maxillary
      alveolar bone for implant insertion necessitating bone augmentation and a sinus
      lift surgery was managed by two students at our institute. Procedures like
      surgical crown lengthening, sinus lifting, and bone augmentation were performed
      by senior faculty with the respective two students' assisting as well as
      following up at the healing phase and reporting progress of healing and any
      possible complications to the supervisor. Students' reported significant
      improvement in decision making skills; time management; interpersonal skills,
      management of cases in an evidence -based interdisciplinary approach as well as
      increase in their confidence in managing complex cases independently. Follow up
      with both cases showed optimum outcome and patients' satisfaction. RESULTS:
      Students' reported significant improvement in decision making skills; time
      management; interpersonal skills, management of cases in an evidence -based
      interdisciplinary approach as well as increase in their confidence in managing
      complex cases independently. Follow up with both cases showed optimum outcome and
      patients' satisfaction. CONCLUSIONS: Exposing students to manage complex oral
      rehabilitation including procedures like sinus lifting and bone augmentation,
      through an evidence-based interdisciplinary approach during the undergraduate
      comprehensive clinical dentistry course enhances their confidence and clinical
      acumen as an independent practitioner.

PMID- 29033527
TI  - Dental students' perceptions of an online learning.
AB  - OBJECTIVES: To identify the readiness of students for online learning, to
      investigate their preference and perception, and to measure the quality of online
      tutorials. MATERIALS AND METHODS: A 14-statement questionnaire was administered
      to fourth year undergraduate dental students in male campus at King Saud
      University who completed preclinical orthodontic course. The students responded
      to each statement by using Likert scale. RESULTS: The results reveal a high
      agreement of students (27.8-31.5% agree and 38.9-50% strongly agree) on a
      possession of necessary computer skills and access to internet. 59.2% and 64.8%
      of the students replied that online flash lectures and procedural videos were
      helpful to their learning, respectively. With respect to students' learning
      preferences, few students preferred online flash lectures (31.5%) and procedural
      videos (17.1%). Most students (38.9% agree and 31.5% strongly agree) preferred a
      combination of traditional teaching methods and online learning. CONCLUSION:
      Overall, student attitudes were positive regarding online learning. The students
      viewed online learning helpful as a supplement to their learning rather than a
      replacement for traditional teaching methods.

PMID- 29033528
TI  - In vitro performance of DIAGNOdent laser fluorescence device for dental calculus
      detection on human tooth root surfaces.
AB  - OBJECTIVE: This study assessed the reproducibility of a red diode laser device,
      and its capability to detect dental calculus in vitro on human tooth root
      surfaces. MATERIAL AND METHODS: On each of 50 extracted teeth, a calculus
      positive and calculus-free root surface was evaluated by two independent
      examiners with a low-power indium gallium arsenide phosphide diode laser
      (DIAGNOdent) fitted with a periodontal probe-like sapphire tip and emitting
      visible red light at 655 nm wavelength. Laser autofluorescence intensity readings
      of examined root surfaces were scored on a 0-99 scale, with duplicate assessments
      performed using the laser probe tip directed both perpendicular and parallel to
      evaluated tooth root surfaces. Pearson correlation coefficients of untransformed
      measurements, and kappa analysis of data dichotomized with a >40 autofluorescence
      intensity threshold, were calculated to assess intra- and inter-examiner
      reproducibility of the laser device. Mean autofluorescence intensity scores of
      calculus-positive and calculus-free root surfaces were evaluated with the
      Student's t-test. RESULTS: Excellent intra- and inter-examiner reproducibility
      was found for DIAGNOdent laser autofluorescence intensity measurements, with
      Pearson correlation coefficients above 94%, and kappa values ranging between 0.96
      and 1.0, for duplicate readings taken with both laser probe tip orientations.
      Significantly higher autofluorescence intensity values were measured when the
      laser probe tip was directed perpendicular, rather than parallel, to tooth root
      surfaces. However, calculus-positive roots, particularly with calculus in
      markedly-raised ledges, yielded significantly greater mean DIAGNOdent laser
      autofluorescence intensity scores than calculus-free surfaces, regardless of
      probe tip orientation. DIAGNOdent autofluorescence intensity values >40 exhibited
      a stronger association with calculus (36.6 odds ratio) then measurements of >=5
      (20.1 odds ratio) when the laser probe tip was advanced parallel to root
      surfaces. CONCLUSIONS: Excellent intra- and inter-examiner reproducibility of
      autofluorescence intensity measurements was obtained with the DIAGNOdent laser
      fluorescence device on human tooth roots. Calculus-positive root surfaces
      exhibited significantly greater DIAGNOdent laser autofluorescence than calculus
      free tooth roots, even with the laser probe tip directed parallel to root
      surfaces. These findings provide further in vitro validation of the potential
      utility of a DIAGNOdent laser fluorescence device for identifying dental calculus
      on human tooth root surfaces.

PMID- 29033529
TI  - Fracture resistance of different primary anterior esthetic crowns.
AB  - PURPOSE: Investigate and compare fracture resistance of four commercially
      available esthetic crowns. METHODS: Sixty-four anterior crowns were used: NuSmile
      Primary crowns (NuSmile, Houston, Tex. USA) (16); Preveneered Cheng Crowns,
      (Orthodontic Technologies Inc., Houston, TX) (16); NuSmile ZR (NuSmile, Houston,
      Tex. USA); and Cheng Crowns zirconia (Orthodontic Technologies Inc., Houston,
      TX). Crowns were mounted and cemented on a negative replica and placed under
      servo hydraulic mechanical universal testing machine. Force was applied at 90
      degrees  with crosshead speed of 1 mm/min until they fractured. Maximum breaking
      loads were recorded. Data was then analyzed using software that measured the
      fracture resistance of the crowns. One-way Analysis of Variance (ANOVA) was used
      to find the differences between the groups and Scheffe post hoc test was used for
      intergroup comparisons. The level of significance was set as p <= 0.05. RESULTS:
      Mean maximum loads were as follows: NuSmile ZR crowns (937.36 + 131.68 N), Cheng
      Zirconia Crowns (751.43 + 102.103 N), NuSmile Primary crowns (482.37 + 76.92),
      and Preveneered Cheng Crowns (415.57 + 12.28). Zirconia crowns the had highest
      fracture resistance compared to preveneered crowns (p < 0.05). No significant
      difference between NuSmile ZR Zirconia and Cheng Crowns zirconia nor between
      NuSmile primary Preveenered and Preveneered Cheng Crowns. CONCLUSION: Zirconia
      crowns showed the highest fracture resistance with NuSmile zirconia crowns to
      being able to resist fracture even under intense pressure of load compared to
      Cheng Crowns zirconia.

PMID- 29033530
TI  - Orthodontic management of a dilacerated central incisor and partially impacted
      canine with unilateral extraction - A case report.
AB  - AIM: To align a dilacerated maxillary central incisor and partially impacted
      canine with unilateral extraction in a young patient with skeletal deep bite.
      MATERIALS AND METHODS: A 14 year old male patient reported to the hospital with
      skeletal deep bite (basal plane angle-17 degrees ), severe horizontal pattern of
      growth (Go-Gn to Sn -22 degrees ), upright maxillary incisors (U1 to NA -26
      degrees ) and retroclined lower incisors (L1 to NB -11 degrees ). The maxillary
      left central incisor was dilacerated, and the maxillary left canine was partially
      impacted. Unilateral extraction of the left maxillary premolar and left
      mandibular central incisor was done. A canine disimpaction spring was used to
      align the impacted canine. An anterior bite plane was given to open the bite.
      RESULTS: Superimposition of lateral cephalogram (T1, T2) revealed bite opening,
      normal overjet and overbite. There was backward rotation of the mandible and
      increase in lower anterior facial height. There was no evidence of root
      resorption or loss of vitality in the dilacerated tooth. Clinically the canine
      was well aligned in the arch. CONCLUSION: Orthodontic management of a dilacerated
      incisor can be done without root resorption or loss of vitality. The partially
      impacted canine was well aligned in the arch. Unilateral extraction can produce
      good treatment results.

PMID- 29033531
TI  - Primal-dual interior point QP-free algorithm for nonlinear constrained
      optimization.
AB  - In this paper, a class of nonlinear constrained optimization problems with both
      inequality and equality constraints is discussed. Based on a simple and effective
      penalty parameter and the idea of primal-dual interior point methods, a QP-free
      algorithm for solving the discussed problems is presented. At each iteration, the
      algorithm needs to solve two or three reduced systems of linear equations with a
      common coefficient matrix, where a slightly new working set technique for judging
      the active set is used to construct the coefficient matrix, and the positive
      definiteness restriction on the Lagrangian Hessian estimate is relaxed. Under
      reasonable conditions, the proposed algorithm is globally and superlinearly
      convergent. During the numerical experiments, by modifying the technique in
      Section 5 of (SIAM J. Optim. 14(1): 173-199, 2003), we introduce a slightly new
      computation measure for the Lagrangian Hessian estimate based on second order
      derivative information, which can satisfy the associated assumptions. Then, the
      proposed algorithm is tested and compared on 59 typical test problems, which
      shows that the proposed algorithm is promising.

PMID- 29033532
TI  - Seeing Is Believing: Using Video Feedback in Cognitive Therapy for Social Anxiety
      Disorder.
AB  - Distorted negative self-images and impressions appear to play a key role in
      maintaining Social Anxiety Disorder (SAD). In previous research, McManus et al.
      (2009) found that video feedback can help people undergoing cognitive therapy for
      SAD (CT-SAD) to develop a more realistic impression of how they appear to others,
      and this was associated with significant improvement in their social anxiety. In
      this paper we first present new data from 47 patients that confirms the value of
      video feedback. Ninety-eighty percent of the patients indicated that they came
      across more favorably than they had predicted after viewing a video of their
      social interactions. Significant reductions in social anxiety were observed
      during the following week and these reductions were larger than those observed
      after control periods. Comparison with our earlier data (McManus et al., 2009)
      suggests we may have improved the effectiveness of video feedback by refining and
      developing our procedures over time. The second part of the paper outlines our
      current strategies for maximizing the impact of video feedback. The strategies
      have evolved in order to help patients with SAD overcome a range of processing
      biases that could otherwise make it difficult for them to spot discrepancies
      between their negative self-imagery and the way they appear on video.

PMID- 29033533
TI  - The Utility of a Connecting Framework to Facilitate Understanding of and Reduce
      the Disparities in Hospice Care Experienced by Racial and Ethnic Minorities.
AB  - Rapidly changing demographics in the United States and diverse cultural beliefs
      impact hospice utilization and end-of-life care. Healthcare professionals and
      clinicians need a connecting framework to understand patients' and their family's
      perspectives regarding utilization of those services. This framework will assist
      healthcare workers in providing culturally sensitive and appropriate information
      to patients nearing the end of life, so that they and their loved ones can make
      informed decisions for optimal care during this passage of life. Considering the
      variables in this framework may also help facilitate communication between
      healthcare professionals and patients and reduce misunderstanding among the
      surviving family members.

PMID- 29033534
TI  - Multicellular tumor spheroids of human uveal melanoma induce genes associated
      with anoikis resistance, lipogenesis, and SSXs.
AB  - PURPOSE: Uveal melanoma (UM) has a high propensity for metastatic spread, and
      approximately 40-50% of patients die of metastatic disease. Metastases can be
      found at the time of diagnosis but also several years after the tumor has been
      removed. The survival of disseminated cancer cells is known to be linked to
      anchorage independence, anoikis resistance, and an adaptive cellular metabolism.
      The cultivation of cancer cells as multicellular tumor spheroids (MCTS) by
      anchorage-independent growth enriches for a more aggressive phenotype. The
      present study examines the differential gene expression of adherent cell
      cultures, non-adherent MCTS cultures, and uncultured tumor biopsies from three
      patients with UM. We elucidate the biochemical differences between the culture
      conditions to find whether the culture of UM as non-adherent MCTS could be linked
      to an anchorage-independent and more aggressive phenotype, thus unravelling
      potential targets for treatment of UM dissemination. METHODS: The various culture
      conditions were evaluated with microarray analysis, quantitative reverse
      transcription polymerase chain reaction (qRT-PCR), RNAscope, immunohistochemistry
      (IHC), and transmission electron microscopy (TEM) followed by gene expression
      bioinformatics. RESULTS: The MCTS cultures displayed traits associated with
      anoikis resistance demonstrated by ANGPTL4 upregulation, and a shift toward a
      lipogenic profile by upregulation of ACOT1 (lipid metabolism), FADS1
      (biosynthesis of unsaturated fatty acids), SC4MOL, DHCR7, LSS (cholesterol
      biosynthesis), OSBPL9 (intracellular lipid receptor), and PLIN2 (lipid storage).
      Additionally, the present study shows marked upregulation of synovial sarcoma X
      breakpoint proteins (SSXs), transcriptional repressors related to the Polycomb
      group (PcG) proteins that modulate epigenetic silencing of genes. CONCLUSIONS:
      The MCTS cultures displayed traits associated with anoikis resistance, a
      metabolic shift toward a lipogenic profile, and upregulation of SSXs, related to
      the PcG proteins.

PMID- 29033535
TI  - Differential association of elevated inflammatory cytokines with postoperative
      fibrous proliferation and neovascularization after unsuccessful vitrectomy in
      eyes with proliferative diabetic retinopathy.
AB  - BACKGROUND: Pars plana vitrectomy is the only treatment for advanced
      proliferative diabetic retinopathy (PDR). However, vitrectomy is not always
      successful despite current progress in vitreoretinal surgical techniques. The aim
      of our study was to investigate whether the vitreal concentrations of MCP-1, IL
      6, IL-8, and VEGF are elevated after unsuccessful vitrectomy in patients with PDR
      and to investigate whether the altered levels of these cytokines are associated
      with the cause for the reoperation. PATIENTS AND METHODS: Vitreous samples were
      collected from 263 eyes of 233 patients: PDR (n=129 eyes), proliferative
      vitreoretinopathy (PVR; n=24 eyes) and nondiabetic controls (n=110 eyes) prior to
      vitrectomy. Vitreous samples were also collected from 14 eyes of 14 patients with
      PDR before vitrectomy and from the same 14 eyes before a second vitrectomy for
      reoperation. The levels of MCP-1, IL-6, IL-8, and VEGF were measured by flow
      cytometry using a cytometric bead array (CBA) assay. RESULTS: The mean
      concentrations of vitreal MCP-1, IL-6, IL-8, and VEGF were significantly higher
      in patients with PDR and PVR (P<0.01). There were significantly high correlations
      among the concentrations of MCP-1, IL-6, and IL-8, whereas the correlation of
      VEGF with the other 3 cytokines was lower. Among the 14 patients who required
      reoperation, the mean vitreal concentrations of MCP-1, IL-6, and IL-8 were higher
      than that at the time of the initial vitrectomy (P<0.01). At the time of the
      reoperation vitrectomy, the mean vitreous level of MCP-1, IL-6, and IL-8 in eyes
      with fibrous proliferation was higher than in those without fibrous proliferation
      (P<0.05). In contrast, VEGF in eyes with neovascular glaucoma (NVG) or anterior
      hyaloidal fibrovascular proliferation (AHFVP) was higher than in the eyes without
      NVG and AHFVP (P<0.05). CONCLUSION: The elevated levels of MCP-1, IL-6, and IL-8
      may be the cause of the postoperative fibrous proliferation. In contrast, VEGF
      may be the cause of the neovascularization after unsuccessful vitrectomy in the
      eyes of PDR patients.

PMID- 29033537
TI  - Quantifying metamorphopsia with M-CHARTS in patients with idiopathic macular
      hole.
AB  - PURPOSE: The purpose of this study was to determine the degree of metamorphopsia
      using M-CHARTSTM in patients with idiopathic macular hole before and after pars
      plana vitrectomy and internal limiting membrane (ILM) peeling. PATIENTS AND
      METHODS: The records of 22 eyes of 22 patients with a full-thickness macular hole
      who underwent pars plana vitrectomy and ILM peeling were reviewed. All patients
      underwent a complete ophthalmic examination including spectral-domain optical
      coherence tomography (OCT). Horizontal metamorphopsia (MH) and vertical
      metamorphopsia (MV) scores were determined using M-CHARTS at the same time. The
      time course of changes in metamorphopsia and the relationship between best
      corrected visual acuity (BCVA) and OCT parameters were assessed. RESULTS: Sealing
      of the macular hole was noted in all eyes after surgery. BCVA improved
      significantly from 1 month after surgery (P<0.001). The MV score was
      significantly higher than the MH score before surgery (P<0.05) and improved
      significantly from 1 month after surgery (P<0.03). The MH score improved
      significantly at 6 months after surgery (P<0.001). The postoperative MV and MH
      scores became closer to one another from 1 month after surgery. Moreover, the MV
      score was higher than the MH score at all postoperative assessments. There was a
      significant correlation between the MV and MH scores at all follow-up
      assessments. There was no significant correlation between BCVA and the MV or MH
      score at any follow-up assessment. CONCLUSION: The satisfaction of the patients
      with macular hole after surgery cannot be necessarily measured by BCVA alone,
      because M-scores were not correlated to BCVA in postoperative evaluation.
      Therefore, evaluation of the MV and MH scores can be an independent treatment
      outcome in addition to BCVA.

PMID- 29033538
TI  - Comparison of a hydrogel corneal inlay and monovision laser in situ
      keratomileusis in presbyopic patients: focus on visual performance and optical
      quality.
AB  - PURPOSE: To compare the visual performance and optical quality after Raindrop
      Near Vision Inlay implantation or monovision LASIK for the correction of
      presbyopia. MATERIALS AND METHODS: In this retrospective case-series study,
      patients previously treated in the nondominant eye with monovision LASIK were
      compared with patients previously implanted with Raindrop Near Vision Inlay. The
      study enrolled 16 inlay and 15 monovision LASIK patients. Uncorrected near visual
      acuity, uncorrected distance visual acuity, binocular stereopsis, patient
      satisfaction, and patient task performance were assessed. RESULTS:
      Postoperatively, the mean spherical equivalent was -0.66 D (0.78 SD) for the
      inlay group and -1.03 D (0.56 SD) for the monovision LASIK group. Monocularly, at
      uncorrected near distances, 60% of inlay patients and 47% of monovision LASIK
      patients achieved >=20/20. Monocularly, at uncorrected far distances, 75% of
      inlay patients and 40% of monovision LASIK patients achieved >=20/32 vision.
      Binocularly, at near distances, 79% of inlay patients and 53% of monovision LASIK
      patients obtained >=20/20 vision. All patients achieved >=20/20 binocularly for
      distance. On average, inlay patients obtained 98 seconds of arc and monovision
      LASIK patients obtained 286 seconds of arc for stereopsis. Most (79%) of the
      inlay patients and 66% of monovision LASIK patients were satisfied with their
      near vision, while 86% of inlay patients and 67% of monovision LASIK patients
      were satisfied with their distance vision. CONCLUSION: Patients receiving corneal
      inlays demonstrated better near and distance visual acuities, binocular
      stereopsis, task performance, and satisfaction, when compared to patients treated
      with monovision LASIK.

PMID- 29033536
TI  - Spotlight on reticular pseudodrusen.
AB  - Age-related macular degeneration (AMD) is a leading cause of vision loss in
      patients >50 years old. The hallmark of the disease is represented by the
      accumulation of extracellular material between retinal pigment epithelium and the
      inner collagenous layer of Bruch's membrane, called drusen. Although identified
      almost 30 years ago, reticular pseudodrusen (RPD) have been recently recognized
      as a distinctive phenotype. Unlike drusen, they are located in the subretinal
      space. RPD are strongly associated with late AMD, especially geographic atrophy,
      type 2 and 3 choroidal neovascularization, which, in turn, are less common in
      typical AMD. RPD identification is not straightforward at fundus examination, and
      their identification should employ at least 2 different imaging modalities. In
      this narrative review, we embrace all aspects of RPD, including history,
      epidemiology, histology, imaging, functional test, natural history and therapy.

PMID- 29033539
TI  - Possible association between subtypes of dry eye disease and seasonal variation.
AB  - PURPOSE: The purpose of this study was to evaluate the influence of seasons on
      the signs and symptoms of dry eye disease (DED). METHODS: This is a cross
      sectional, case-control study, and participants were non-DED subjects (n=1,916,
      mean age 54.4+/-14.4 years) and DED patients (n=684, 54.2+/-12.1 years) visiting
      six eye clinics at various practices and locations in Japan. We evaluated the
      signs and symptoms of DED and the seasons with the most severe results were
      compared to those with the least severe results in both groups. Main outcome
      measures were differences in the severity of the signs and symptoms of DED
      between the most and least severe seasons. RESULTS: The majority of DED symptoms
      were most severe during spring and least severe in summer. Significant
      differences between these two seasons were found for irritation (P=0.001), pain
      (P=0.007), blurring (P=0.000), and photophobia (P=0.007) in the DED group.
      Superficial punctate keratopathy (P=0.001) and tear break-up time (BUT; P=0.000)
      results also indicated that DED was most severe in spring. In contrast, fewer
      patients had low Schirmer test results in spring, although this was not
      statistically significant (P=0.061). CONCLUSION: Our results demonstrated that
      the severity of DED is seasonal, which may explain the increase of short BUT-type
      DED cases observed in spring when air pollen counts are highest.

PMID- 29033540
TI  - Assay development and high-throughput screening for small molecule inhibitors of
      a Vibrio cholerae stress response pathway.
AB  - Antibiotics are important adjuncts to oral rehydration therapy in cholera disease
      management. However, due to the rapid emergence of resistance to the antibiotics
      used to treat cholera, therapeutic options are becoming limited. Therefore, there
      is a critical need to develop additional therapeutics to aid in the treatment of
      cholera. Previous studies showed that the extracytoplasmic stress response
      (sigmaE) pathway of Vibrio cholerae is required for full virulence of the
      organism. The pathway is also required for bacterial growth in the presence of
      ethanol. Therefore, we exploited this ethanol sensitivity phenotype in order to
      develop a screen for inhibitors of the pathway, with the aim of also inhibiting
      virulence of the pathogen. Here we describe the optimization and implementation
      of our high-throughput screening strategy. From a primary screen of over 100,000
      compounds, we have identified seven compounds that validated the growth
      phenotypes from the primary and counterscreens. These compounds have the
      potential to be developed into therapeutic agents for cholera and will also be
      valuable probes for uncovering basic molecular mechanisms of an important cause
      of diarrheal disease.

PMID- 29033541
TI  - Dexmedetomidine reduces the neuronal apoptosis related to cardiopulmonary bypass
      by inhibiting activation of the JAK2-STAT3 pathway.
AB  - Cardiopulmonary bypass (CPB) constitutes one of the primary methodologies
      pertaining to cardiac surgery. However, this form of surgery can cause damage to
      the body. Many studies have reported that dexmedetomidine confers cerebral
      protection. In this study, we aimed to investigate the effect and mechanism of
      dexmedetomidine on neuronal apoptosis caused by CPB. Here, rats were treated with
      different doses of dexmedetomidine by intravenous infusion 2 hours after CPB. We
      observed that dexmedetomidine treatment to rats reduces the S100beta, NSE levels
      in plasma, and neuronal apoptosis following CPB in a dose-dependent manner.
      Furthermore, we observed that the beneficial effect of dexmedetomidine treatment
      following CPB was associated with a reduction in IL6, an inflammatory cytokine in
      plasma and cortex. Our results suggest that dexmedetomidine provides
      neuroprotective effects by inhibiting inflammation and reducing neuronal
      apoptosis. There was a correlation between the protective effect on the brain and
      the dose of dexmedetomidine. In addition, dexmedetomidine administration inhibits
      phosphorylation of JAK2 and STAT3 proteins in the hippocampus of rats 2 hours
      after CPB. Therefore, we speculate that the JAK2-STAT3 pathway plays an important
      role in the neuroprotective effects of dexmedetomidine following brain injury
      induced by CPB.

PMID- 29033543
TI  - Effect of echinacoside on kidney fibrosis by inhibition of TGF-beta1/Smads
      signaling pathway in the db/db mice model of diabetic nephropathy.
AB  - Kidney fibrosis and renal tubular epithelial-to-mesenchymal transition (EMT) are
      the main pathological changes of diabetic nephropathy (DN), which eventually
      leads to end-stage renal disease. Previous studies have suggested that
      echinacoside (ECH) is antifibrotic in the liver. However, the effect of ECH on
      kidney fibrosis in DN and its mechanisms are unknown. This study was performed to
      explore the effect of ECH on kidney fibrosis and also the molecular mechanisms of
      ECH in a db/db mice model of DN. Our results showed that, relative to db/db mice,
      the mice in the ECH group had an improved general state and reduced blood glucose
      and 24-hour urinary protein levels. The deterioration of renal function was
      delayed due to treatment with ECH. We also observed that ECH can improve
      histopathological findings in the kidneys of db/db mice, including collagen
      deposition, mesangial cell and mesangial matrix hyperplasia, basement membrane
      thickening, and podocyte reduction. Moreover, ECH inhibited the TGF-beta1/Smads
      signaling pathway, downregulated fibronectin (FN), collagen IV, and alpha-smooth
      muscle actin (alpha-SMA) levels, and upregulated E-cadherin level in the db/db
      mice model of DN. Our findings indicate that ECH has a therapeutic effect on DN,
      including the inhibition of renal tubular EMT and kidney fibrosis. Furthermore,
      ECH inhibits kidney fibrosis through regulation of the TGF-beta1/Smads signaling
      pathway.

PMID- 29033542
TI  - Axitinib in the treatment of renal cell carcinoma: design, development, and place
      in therapy.
AB  - Since 2005, the approved first-line treatment of metastatic renal cell carcinoma
      consists in tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial
      growth factor receptors (VEGFRs). Axitinib is an oral second-generation TKI and a
      potent VEGFR inhibitor with a half maximal inhibitory concentration for the VEGF
      family receptors 10-fold lower than other TKIs. Axitinib activity in renal cell
      carcinoma (RCC) patients has been studied in various settings and particularly as
      second-line treatment. In this setting, axitinib with clinically based dose
      escalation compared to sorafenib has demonstrated an improvement in progression
      free survival in a randomized Phase III trial leading to US Food and Drug
      Administration approval. In the first-line setting, axitinib failed to
      demonstrate improved efficacy over sorafenib, but the field of RCC treatment is
      rapidly changing with novel TKIs as cabozantinib or the emergence of check point
      inhibitors as nivolumab and the place of axitinib in therapy is therefore
      challenged. In this review, we focus on axitinib pharmacological and clinical
      properties in RCC patients and discuss its place in the treatment of patients
      with RCC.

PMID- 29033544
TI  - Eluxadoline in the treatment of diarrhea-predominant irritable bowel syndrome.
AB  - Eluxadoline is a novel drug approved for the management of diarrhea predominant
      irritable bowel syndrome (IBS-D). It has unique pharmacology and works on three
      different opioid receptors. Several Phase II and III clinical trials have
      demonstrated eluxadoline's efficacy in reducing symptoms related to IBS-D.
      Clinical trial results and postmarketing reports show a risk of pancreatitis in
      patients without a gallbladder or those abusing alcohol. This review article will
      include information on clinical trial results related to IBS-D management as well
      as eluxadoline's limitations.

PMID- 29033545
TI  - Downregulation of A20 increases the cytotoxicity of IFN-gamma in hepatocellular
      carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) is a highly fatal disease mandating development of
      novel, effective therapeutic strategy. Interferon-gamma (IFN-gamma) is a
      pleiotropic cytokine with immunomodulatory, antiviral, and antitumor effects.
      Although IFN-gamma is a promising antitumor agent, its application is limited by
      resistance in tumor cells. A20 is a zinc-finger protein that was initially
      identified as a gene product induced by tumor necrosis factor alpha in human
      umbilical vein endothelial cells. In this study, we found that silencing of A20
      combined with IFN-gamma significantly represses cell viability, and induces
      apoptosis and cell-cycle arrest in HCC cells. By investigating mechanisms
      implicated in A20 and IFN-gamma-mediated signaling pathways, we revealed that the
      phosphoinositide 3-kinase/Akt signaling pathway and antiapoptotic B-cell lymphoma
      2 proteins were repressed. Moreover, we also found that phosphorylation of STAT1
      and STAT3 was significantly enhanced after the downregulation of A20 in
      combination with treatment of IFN-gamma. Inhibitor of STAT1 but not STAT3 could
      block the antitumor effect of IFN-gamma. Therefore, targeting A20 enhances the
      cytotoxicity of IFN-gamma against HCC cells and may present a promising
      therapeutic strategy for HCC.

PMID- 29033547
TI  - New tablet formulation of tacrolimus with smaller interindividual variability may
      become a better treatment option than the conventional capsule formulation in
      organ transplant patients.
AB  - To evaluate the pharmacokinetic (PK) and tolerability profiles of a new tablet
      formulation of tacrolimus and its interindividual variability (IIV) in the
      systemic exposure, and to compare them with those of the conventional capsule
      formulation, a randomized, open-label, two-treatment, two-period, two-sequence,
      crossover study was performed in 47 healthy males. The capsule or tablet
      formulation of tacrolimus was orally administered, and serial blood samples were
      collected up to 96 hours after dosing. Whole-blood tacrolimus concentration was
      determined using liquid chromatography-tandem mass spectrometry. The maximum
      whole-blood tacrolimus concentration (Cmax) and the area under the whole-blood
      tacrolimus concentration-time curve from 0 hour to the last quantifiable
      concentration (AUClast) were compared between the two formulations. The
      similarity factor (f2) of the in vitro dissolution profiles was calculated. The
      geometric mean ratio (90% confidence interval) of tablet to capsule was 0.9680
      (0.8873-1.0560) and 1.0322 (0.9359-1.1385) for Cmax and AUClast, respectively.
      The IIV of Cmax and AUClast of the tablet was smaller than the capsule. The f2
      values were >50 in all media. Both formulations were well tolerated. Thus, the
      tablet formulation of tacrolimus has smaller IIV in the systemic exposure than
      capsule, while having comparable PK and tolerability profiles, which may render
      it as a better treatment option for organ transplant patients.

PMID- 29033546
TI  - Safety and efficacy profile of pembrolizumab in solid cancer: pooled reanalysis
      based on randomized controlled trials.
AB  - BACKGROUND: The aim of the present review is to systematically evaluate the
      efficacy and safety of pembrolizumab by analyzing survival outcomes and at the
      same time, to present evidence for future clinical applications of anti
      programmed cell death protein 1 (anti-PD-1) antibodies by analyzing the efficacy
      and safety of pembrolizumab. METHODS: A comprehensive literature search of
      PubMed, Medline, and Embase was performed for all relevant clinical trials. In
      this study, adverse events of any grades and grades >=3 were summarized and
      calculated for event rates. For controlled trials, odd ratios (ORs) were
      calculated to determine the role of pembrolizumab in adverse events. The Kaplan
      Meier survival curves were extracted for hazard ratio (HR) calculation and
      survival outcomes were measured by progression-free survival (PFS). RESULTS: A
      total of 3,953 patients were included in safety analyses. The results indicated
      that the overall incidence of any treatment emergent adverse events was 74.3%
      (95% confidence interval [CI]: 0.671-0.805). The efficacy analysis involving 915
      patients with advanced melanoma suggested that 10 mg/kg of pembrolizumab every 3
      weeks could improve patients' PFS (HR =0.73, 95% CI: 0.64-0.83). CONCLUSION:
      Pembrolizumab is a promising therapeutic option that could bring better survival
      outcomes but, at the same time, leads to higher frequency of some adverse events.

PMID- 29033549
TI  - Reliability of patient-reported outcome instruments in US adults with hemophilia:
      the Pain, Functional Impairment and Quality of life (P-FiQ) study.
AB  - BACKGROUND: Hemophilia is marked by frequent joint bleeding, resulting in pain
      and functional impairment. OBJECTIVE: This study aimed to assess the reliability
      of five patient-reported outcome (PRO) instruments in people with hemophilia
      (PWH) in a non-bleeding state. METHODS: Adult male PWH of any severity and
      inhibitor status, with a history of joint pain or bleeding, completed a pain
      history and five PRO instruments (EQ-5D-5L, Brief Pain Inventory v2 [BPI],
      International Physical Activity Questionnaire [IPAQ], Short Form 36 Health Survey
      v2 [SF-36v2], and Hemophilia Activities List [HAL]) during their routine
      comprehensive care visit. Patients were approached to complete the PRO
      instruments again at the end of their visit while in a similar non-bleeding
      state. Concordance of individual questionnaire items and correlation between
      domain scores were assessed using intra-class correlation coefficient (ICC).
      RESULTS: Participants completing the retest (n=164) had a median age of 33.9
      years. Median time for completion of the initial survey with PRO instruments was
      36.0 minutes and for the five PRO instruments, median retest time was 21.0
      minutes. The majority of participants had hemophilia A (74.4%), were white and
      non-Hispanic (72.6%), and self-reported arthritis/bone/joint problems (61%).
      Median/mean test-retest concordance was EQ-5D-5L 80.0%/79.1%, BPI 54.5%/58.9%,
      IPAQ 100%/100%, SF-36v2 77.8%/76.4%, and HAL 77.4%/75.9%. ICCs for test-retest
      reliability were EQ-5D-5L index 0.890; BPI - severity 0.950; BPI - interference
      0.920; IPAQ total activity 0.940; SF-36v2 overall health 0.910; HAL total score
      0.970. CONCLUSION: All five PRO scales showed acceptable test-retest reliability
      in adult PWH. Therefore, the choice of instrument to be used for research or
      clinical care should be driven by instrument characteristics other than
      reliability.

PMID- 29033550
TI  - Coach to cope: feasibility of a life coaching program for young adults with
      cystic fibrosis.
AB  - BACKGROUND: Over the last two decades, lifespan has increased significantly for
      people living with cystic fibrosis (CF). However, several studies have
      demonstrated that many young adults with CF report mental health problems and
      poor adherence to their prescribed treatments, challenging their long-term
      physical health. Treatment guidelines recommend interventions to improve
      adherence and self-management. The aim of this study was to test the feasibility
      of a life coaching intervention for young adults with CF. METHODS: A randomized,
      controlled feasibility study was conducted at the CF Center at Copenhagen
      University Hospital, Rigshospitalet. Participants were young adults with CF, aged
      18-30 years without severe intellectual impairments. Participants were randomized
      to either life coaching or standard care. The intervention consisted of up to 10
      individual, face-to-face or telephone coaching sessions over a period of 1 year.
      Primary outcomes were recruitment success, acceptability, adherence to the
      intervention, and retention rates. Secondary outcome measures included health
      related quality of life, adherence to treatment, self-efficacy, pulmonary
      function, body mass index, and blood glucose values. RESULTS: Among the 85
      eligible patients approached, 40 (47%) were enrolled and randomized to the
      intervention or control group; two patients subsequently withdrew consent.
      Retention rates after 5 and 10 coaching sessions were 67% and 50%, respectively.
      Reasons for stopping the intervention included lack of time, poor health,
      perceiving coaching as not helpful, lack of motivation, and no need for further
      coaching. Coaching was primarily face-to-face (68%). No significant differences
      were found between the groups on any of the secondary outcomes. CONCLUSION: Both
      telephone and face-to-face coaching were convenient for participants, with 50%
      receiving the maximum offered coaching sessions. However, the dropout rate early
      in the intervention was a concern. In future studies, eligible participants
      should be screened for their interest and perceived need for support and life
      coaching before enrollment.

PMID- 29033552
TI  - Therapy preferences of patients with lung and colon cancer: a discrete choice
      experiment.
AB  - OBJECTIVES: There is increasing interest in studies that examine patient
      preferences to measure health-related outcomes. Understanding patients'
      preferences can improve the treatment process and is particularly relevant for
      oncology. In this study, we aimed to identify the subgroup-specific treatment
      preferences of German patients with lung cancer (LC) or colorectal cancer (CRC).
      METHODS: Six discrete choice experiment (DCE) attributes were established on the
      basis of a systematic literature review and qualitative interviews. The DCE
      analyses comprised generalized linear mixed-effects model and latent class mixed
      logit model. RESULTS: The study cohort comprised 310 patients (194 with LC, 108
      with CRC, 8 with both types of cancer) with a median age of 63 (SD =10.66) years.
      The generalized linear mixed-effects model showed a significant (P<0.05) degree
      of association for all of the tested attributes. "Strongly increased life
      expectancy" was the attribute given the greatest weight by all patient groups.
      Using latent class mixed logit model analysis, we identified three classes of
      patients. Patients who were better informed tended to prefer a more balanced
      relationship between length and health-related quality of life (HRQoL) than those
      who were less informed. Class 2 (LC patients with low HRQoL who had undergone
      surgery) gave a very strong weighting to increased length of life. We deduced
      from Class 3 patients that those with a relatively good life expectancy (CRC
      compared with LC) gave a greater weight to moderate effects on HRQoL than to a
      longer life. CONCLUSION: Overall survival was the most important attribute of
      therapy for patients with LC or CRC. Differences in treatment preferences between
      subgroups should be considered in regard to treatment and development of
      guidelines. Patients' preferences were not affected by sex or age, but were
      affected by the cancer type, HRQoL, surgery status, and the main source of
      information on the disease.

PMID- 29033553
TI  - A critical analysis of national policies, systems, and structures of patient
      empowerment in England and Greece.
AB  - BACKGROUND: Comparison of patient empowerment (PE) policies in European countries
      can provide evidence for improvement and reform across different health systems.
      It may also influence patient and public involvement, patient experience,
      preference, and adherence. OBJECTIVE: The objective of this study was to compare
      PE within national policies, systems, and structures in England and Greece for
      achieving integrated people-centered health services. METHODS: We performed a
      critical search and review of policy and legislation papers in English and Greek
      languages. This included 1) general health policy and systems papers, 2) PE,
      patient and/or public involvement or patients' rights policy and legislation
      (1990-2015), and 3) comparative or discussion papers for England and/or Greece.
      RESULTS: A total of 102 papers on PE policies, systems, and structures were
      identified initially; 80 papers were included, in which 46 were policy,
      legislative, and discussion papers about England, 21 were policy, legislation,
      and discussion papers about Greece, and 13 were comparative or discussion papers
      including both the countries. In England, National Health Service policies
      emphasized patient-centered services, involvement, and empowerment, with recent
      focus on patients' rights; while in Greece, they emphasized patients' rights and
      quality of services, with recent mentions on empowerment. The health ombudsman is
      a very important organization across countries; however, it may be more powerful
      in Greece, because of the nonexistence of local mediating bodies. Micro
      structures at trusts/hospitals are comparable, but legislation gives more power
      to the local structures in Greece. CONCLUSION: PE policies and systems have been
      developed and expressed differently in these countries. However, PE similarities,
      comparable dimensions and mechanisms, were identified. For both the countries,
      comparative research and these findings could be beneficial in building
      connections and relationships, contributing to wider European and international
      developments on PE, involvement, and patients' rights and further impact on
      patient preferences and adherence.

PMID- 29033551
TI  - Healthcare provider relational quality is associated with better self-management
      and less treatment burden in people with multiple chronic conditions.
AB  - PURPOSE: Having multiple chronic conditions (MCCs) can lead to appreciable
      treatment and self-management burden. Healthcare provider relational quality
      (HPRQ) - the communicative and interpersonal skill of the provider - may mitigate
      treatment burden and promote self-management. The objectives of this study were
      to 1) identify the associations between HPRQ, treatment burden, and psychosocial
      outcomes in adults with MCCs, and 2) determine if certain indicators of HPRQ are
      more strongly associated than others with these outcomes. PATIENTS AND METHODS:
      This is a cross-sectional survey study of 332 people with MCCs. Patients
      completed a 7-item measure of HPRQ and measures of treatment and self-management
      burden, chronic condition distress, self-efficacy, provider satisfaction,
      medication adherence, and physical and mental health. Associations between HPRQ,
      treatment burden, and psychosocial outcomes were determined using correlational
      analyses and independent samples t-tests, which were repeated in item-level
      analyses to explore which indicators of HPRQ were most strongly associated with
      the outcomes. RESULTS: Most respondents (69%) were diagnosed with >=3 chronic
      conditions. Better HPRQ was found to be associated with less treatment and self
      management burden and better psychosocial outcomes (P<0.001), even after
      controlling for physical and mental health. Those reporting 100% adherence to
      prescribed medications had higher HPRQ scores than those reporting less than
      perfect adherence (P<0.001). HPRQ items showing the strongest associations with
      outcomes were "my healthcare provider spends enough time with me", "my healthcare
      provider listens carefully to me", and "I have trust in my healthcare provider".
      CONCLUSION: Good communication and interpersonal skills of healthcare providers
      may lessen feelings of treatment burden and empower patients to feel confident in
      their self-management. Patient trust in the provider is an important element of
      HPRQ. Educating healthcare providers about the importance of interpersonal and
      relational skills could lead to more patient-centered care.

PMID- 29033554
TI  - Validation of the Italian version of the Patient Reported Experience Measures for
      intermediate care services.
AB  - BACKGROUND: Intermediate care (IC) services are a key component of integrated
      care for elderly people, providing a link between hospital and home through
      provision of rehabilitation and health and social care. The Patient Reported
      Experience Measures (PREMs) are designed to measure user experience of care in IC
      settings. OBJECTIVE: To examine the feasibility and the scaling properties of the
      Italian version of PREMs questionnaires for use in IC services. METHODS: A cross
      sectional survey was conducted on consecutive users of 1 home-based and 4 bed
      based IC services in Emilia-Romagna (Italy). The main outcome measure was the
      PREMs questionnaire results. PREMs for each home- and bed-based IC services were
      translated, back-translated, and adapted through consensus among the members of
      the advisory board and pilot testing of face validity in 15 patients. A total of
      199 questionnaires were returned from users of bed-based services and 185 were
      returned by mail from users of home-based services. The return rates and
      responses were examined. Mokken analysis was used to examine the scaling
      properties of the PREMs. RESULTS: Analysis performed on the bed-based PREMs
      (N=154) revealed that 13 items measured the same construct and formed a moderate
      strength scale (Loevinger H=0.488) with good reliability (Cronbach's alpha
      =0.843). Analysis of home-based PREMs (N=134 records) revealed that 15 items
      constituted a strong scale (Loevinger H=0.543) with good reliability (Cronbach's
      alpha =0.875). CONCLUSION: The Italian versions of the bed- and home-based IC
      PREMs questionnaires proved to be valid and reliable tools to assess patients'
      experience of care. Future plans include monitoring user experience over time in
      the same facilities and in other Italian IC settings for between-service
      benchmarking.

PMID- 29033548
TI  - The new era of nanotechnology, an alternative to change cancer treatment.
AB  - In the last few years, nanostructures have gained considerable interest for the
      safe delivery of therapeutic agents. Several therapeutic approaches have been
      reported, such as molecular diagnosis, disease detection, nanoscale immunotherapy
      and anticancer drug delivery that could be integrated into clinical use. The
      current paper aims to highlight the background that supports the use of
      nanoparticles conjugated with different types of therapeutic agents, applicable
      in targeted therapy and cancer research, with a special emphasis on hematological
      malignancies. A particular key point is the functional characterization of
      nonviral delivery systems, such as gold nanoparticles, liposomes and dendrimers.
      The paper also presents relevant published data related to microRNA and RNA
      interference delivery using nanoparticles in cancer therapy.

PMID- 29033555
TI  - Treatment adherence in hemophilia.
AB  - Prophylactic clotting-factor regimens reduce the occurrence of bleeding episodes
      and maintain joint health in individuals with moderate and severe hemophilia.
      However, these outcomes are only achieved with adherence to prescribed
      prophylaxis regimens. There are several types of barriers to adherence related to
      key patient, condition, treatment, health-care system, and/or socioeconomic
      variables. Notably, health-care professionals may not prescribe prophylaxis if
      they perceive that a patient will be nonadherent. Prophylactic treatment
      strategies should be developed with the patient and family, focused on
      individualized treatment goals. Personalized strategies are needed to reinforce
      the importance of and encourage confidence in administering the regular infusions
      required for prophylactic therapy. These strategies may include verbal and
      written information delivered by health-care professionals, peers, and inter
      active media. The advent of extended half-life clotting factors requiring less
      frequent infusion may improve adherence.

PMID- 29033556
TI  - Swallowing difficulties with medication intake assessed with a novel self-report
      questionnaire in patients with systemic sclerosis - a cross-sectional population
      study.
AB  - OBJECTIVES: To assess subjective swallowing difficulties (SD) with medication
      intake and their practical consequences in patients suffering from systemic
      sclerosis (SSc) with a novel self-report questionnaire. DESIGN AND SETTING: Based
      on a systematic literature review, we developed a self-report questionnaire and
      got it approved by an expert panel. Subsequently, we sent the questionnaire by
      post mail to SSc patients of the European Center for the Rehabilitation of
      Scleroderma Rheinfelden, Switzerland. PARTICIPANTS: Patients were eligible if
      they were diagnosed with SSc, treated at the center, and were of age >=18 years
      at the study start. MAIN OUTCOME MEASURES: Prevalence and pattern of SD with oral
      medication intake, including localization and intensity of complaints. RESULTS:
      The questionnaire consisted of 30 items divided into five sections Complaints,
      Intensity, Localization, Coping strategies, and Adherence. Of the 64 SSc patients
      eligible in 2014, 43 (67%) returned the questionnaire. Twenty patients reported
      SD with medication intake (prevalence 47%), either currently (11; 26%) or in the
      past that had been overcome (9; 21%). Self-reported SD were localized mostly in
      the larynx (43%) and esophagus (34%). They were of moderate (45%) or strong to
      unbearable intensity (25%). Modification of the dosage form was reported in 40%
      of cases with SD. Adherence was poor for 20 (47%) patients and was not associated
      with SD (p=0.148). CONCLUSION: Our novel self-report questionnaire is able to
      assess the pattern of complaints linked to medication intake, that is,
      localization and intensity. It may serve as a guide for health care professionals
      in selecting the most suitable therapy option, enabling tailored counseling to
      reduce inappropriate medication modifications.

PMID- 29033557
TI  - The correlates of social capital and adherence to healthy lifestyle in patients
      with coronary heart disease.
AB  - OBJECTIVE: To investigate the correlates of social capital and adherence to
      healthy lifestyle in patients with coronary heart disease (CHD). METHODS: This
      register-based, cross-sectional study consisted of individuals diagnosed with CHD
      at four community health service centers, Shanghai, China, between April and July
      2016 (n=609). The sociodemographic characteristics, social capital, adherence to
      physical activity, and nutrition data were obtained through face-to-face
      interviews. Social capital was assessed by social participation, social
      networking, social support, social trust, and sense of belonging. Physical
      activity and nutrition were measured with the Health-Promoting Lifestyle Profile
      II. The independent two-sample t-test and Pearson's correlations were used to
      analyze associations among variables. Hierarchical multiple regression models
      were used to evaluate effects of social capital on adherence to physical activity
      and nutrition. RESULTS: The average age of the sample was 60.87 (standard
      deviation [SD] =6.91), with 54.4% being male and 45.6% female. The average score
      of physical activity and nutrition were 2.38 (SD =0.59) and 2.78 (SD =0.50),
      respectively. The final model significantly explained 28.9% of variance in
      physical activity (F=34.96, P<0.001) and 30.5% of variance in nutrition (F=37.73,
      P<0.001). Most of the subdimensions of social capital were significantly
      associated with physical activity and nutrition, after controlling for marital
      status and education level. CONCLUSION: The results suggested that social capital
      was the correlate of adherence to long-term healthy lifestyle, including physical
      activity and nutrition. These findings highlight the need to take into account
      social capital in developing intervention strategies to improve the adherence to
      the long-term healthy lifestyle for patients with CHD.

PMID- 29033558
TI  - Effect of surface organic coatings of cellulose nanocrystals on the viability of
      mammalian cell lines.
AB  - Cellulose nanocrystals (CNCs) have emerged as promising candidates for a number
      of bio-applications. Surface modification of CNCs continues to gain significant
      research interest as it imparts new properties to the surface of the nanocrystals
      for the design of multifunctional CNCs-based materials. A small chemical surface
      modification can potentially lead to drastic behavioral changes of cell-material
      interactions thereby affecting the intended bio-application. In this work,
      unmodified CNCs were covalently decorated with four different organic moieties
      such as a diaminobutane fragment, a cyclic oligosaccharide (beta-cyclodextrin), a
      thermoresponsive polymer (poly[N-isopropylacrylamide]), and a cationic
      aminomethacrylamide-based polymer using different synthetic covalent methods. The
      effect of surface coatings of CNCs and the respective dose-response of the above
      organic moieties on the cell viability were evaluated on mammalian cell cultures
      (J774A.1 and MFC-7), using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe-nyltetrazolium
      bromide and lactate dehydrogenase assays. Overall, the results indicated that
      cells exposed to surface-coated CNCs for 24 h did not display major changes in
      cell viability, membrane permeability as well as cell morphology. However, with
      longer exposure, all these parameters were somewhat affected, which appears not
      to be correlated with either anionic or cationic surface coatings of CNCs used in
      this study.

PMID- 29033560
TI  - Proactive palliative care for patients with COPD (PROLONG): a pragmatic cluster
      controlled trial.
AB  - BACKGROUND AND AIM: Patients with advanced chronic obstructive pulmonary disease
      (COPD) have poor quality of life. The aim of this study was to assess the effects
      of proactive palliative care on the well-being of these patients. TRIAL
      REGISTRATION: This trial is registered with the Netherlands Trial Register,
      NTR4037. PATIENTS AND METHODS: A pragmatic cluster controlled trial (quasi
      experimental design) was performed with hospitals as cluster (three intervention
      and three control) and a pretrial assessment was performed. Hospitals were
      selected for the intervention group based on the presence of a specialized
      palliative care team (SPCT). To control for confounders, a pretrial assessment
      was performed in which hospitals were compared on baseline characteristics.
      Patients with COPD with poor prognosis were recruited during hospitalization for
      acute exacerbation. All patients received usual care while patients in the
      intervention group received additional proactive palliative care in monthly
      meetings with an SPCT. Our primary outcome was change in quality of life score
      after 3 months, which was measured using the St George Respiratory Questionnaire
      (SGRQ). Secondary outcomes were, among others, quality of life at 6, 9 and 12
      months; readmissions: survival; and having made advance care planning (ACP)
      choices. All analyses were performed following the principle of intention to
      treat. RESULTS: During the year 2014, 228 patients (90 intervention and 138
      control) were recruited and at 3 months, 163 patients (67 intervention and 96
      control) completed the SGRQ. There was no significant difference in change scores
      of the SGRQ total at 3 months between groups (-0.79 [95% CI, -4.61 to 3.34],
      p=0.70). However, patients who received proactive palliative care experienced
      less impact of their COPD (SGRQ impact subscale) at 6 months (-6.22 [-11.73 to 
      0.71], p=0.04) and had more often made ACP choices (adjusted odds ratio 3.26
      [1.49-7.14], p=0.003). Other secondary outcomes were not significantly different.
      CONCLUSION: Proactive palliative care did not improve the overall quality of life
      of patients with COPD. However, patients more often made ACP choices which may
      lead to better quality of care toward the end of life.

PMID- 29033559
TI  - Pressure injuries in elderly with acute myocardial infarction.
AB  - OBJECTIVES: To assess pressure injury (PI) incidence among patients hospitalized
      for acute myocardial infarction (AMI) in an intensive coronary care unit (ICCU)
      and to detect the impact of specific risk factors on the development of PI in
      this clinical setting. PATIENTS AND METHODS: Prospective cohort study in ICCU
      setting. Patients admitted for AMI: patients mean age 67.5+/-11.5 years (n=165).
      Norton Scale, Mini Nutritional Assessment (MNA), demographic, clinical and
      biochemical data collected at the time of ICCU admission have been tested in a
      logistic model to assess the odds ratios (ORs) of PI risk development. The
      jackknifed area under the receiver operating characteristic curve (AUC) and the
      decision curve analysis have been employed to assess the additive predictive
      value of a factor. RESULTS: Twenty-seven (16.3%) patients developed PIs. An
      increased PI risk was associated with advanced age (OR =2.5 every 10-year
      increase; 95% CI =1.1-5.7), while probability of PI development was reduced in
      patients with higher left ventricular ejection fraction (LVEF) (OR =0.4 every 5%
      increase; 95% CI =0.24-0.66), MNA score (OR =0.65 every unit change; 95% CI =0.44
      0.95) and Norton Scale score (OR =0.7 every unit change; 95% CI =0.57-0.88). The
      AUC and the decision curve analysis showed that LVEF inclusion improved the
      discrimination power and the clinical net benefit of the final model. CONCLUSION:
      Age, LVEF, Norton Scale and MNA scores have a strong and independent clinical
      value as predictors of in-hospital PI development in patients with AMI. This
      finding has the potential to improve the clinical management of patients admitted
      in ICCU.

PMID- 29033561
TI  - Specific IgA against Pseudomonas aeruginosa in severe COPD.
AB  - BACKGROUND: The bronchial mucosa is protected by a specialized immune system
      focused on the prevention of colonization and infection by potentially pathogenic
      microorganisms (PPMs). Immunoglobulin A (IgA) is the principal antibody involved
      in this mechanism. A defective immune barrier may facilitate the recurrent
      presence of PPMs in COPD. PURPOSE: The aim of this study was to determine IgA
      mediated bronchial specific immune responses against Pseudomonas aeruginosa in
      stable patients with severe disease. METHODS: COPD patients with good-quality
      sputum samples obtained during stability were included and classified according
      to the presence or absence of chronic bronchial colonization by P. aeruginosa.
      Levels of specific IgA for P. aeruginosa in sputum were determined by ELISA and
      expressed as ratios, using the pooled level of 10 healthy subjects as reference
      (optical density450 patient/control). RESULTS: Thirty-six stable COPD patients
      were included, 15 of whom had chronic colonization by P. aeruginosa. Levels of
      specific IgA against P. aeruginosa in stable non-colonized patients were lower
      than those in healthy subjects (IgA ratio: median =0.15 [interquartile range
      {IQR} 0.05-0.36]). Colonized patients had higher levels, (1.56 [IQR 0.59-2.79])
      (p<0.001, Mann-Whitney U test), with figures equivalent but not exceeding the
      reference value. CONCLUSION: IgA-based immune response against P. aeruginosa was
      low in severe COPD patients. Levels of specific IgA against this microorganism
      were higher in colonized patients, but did not attain clear-cut levels above the
      reference. An impaired local response against P. aeruginosa may favor chronic
      colonization and recurrent infections in severe COPD.

PMID- 29033562
TI  - Associations between the psychological health of patients and carers in advanced
      COPD.
AB  - OBJECTIVE: Anxiety and depression are highly prevalent in patients with COPD and
      their informal carers, and associated with numerous risk factors. However, few
      studies have investigated these in primary care or the link between patient and
      carer anxiety and depression. We aimed to determine this association and factors
      associated with anxiety and depression in patients, carers, and both (dyads), in
      a population-based sample. MATERIALS AND METHODS: This was a prospective, cross
      sectional study of 119 advanced COPD patients and their carers. Patient and carer
      scores >=8 on the Hospital Anxiety and Depression Scale defined symptoms of
      anxiety and depression, chi2 tests determined associations between patient and
      carer symptoms of anxiety/depression, and chi2 and independent t-tests for
      normally distributed variables (otherwise Mann-Whitney U tests) were used to
      identify other variables significantly associated with these symptoms in the
      patient or carer. Patient-carer dyads were categorized into four groups relating
      to the presence of anxious/depressive symptoms in: both patient and carer,
      patient only, carer only, and neither. Factors associated with dyad symptoms of
      anxiety/depression were determined with chi2 tests and one-way analysis of
      variance for normally distributed variables (otherwise Kruskal-Wallis tests).
      RESULTS: Prevalence of symptoms of anxiety and depression was 46.4% (n=52) and
      42.9% (n=48) in patients, and 46% (n=52) and 23% (n=26) in carers, respectively.
      Patient and carer symptoms of anxiety/depression were significantly associated.
      Anxious and depressive symptoms in the patient were also significantly associated
      with more physical comorbidities, more exacerbations, greater dyspnea, greater
      fatigue, poor mastery, and depressive symptoms with younger age. Symptoms of
      carer anxiety were significantly associated with being female and
      separated/divorced/widowed, and depressive symptoms with younger age, higher
      educational level, and more physical comorbidities, and symptoms of carer anxiety
      and depression with more unmet support needs, greater subjective caring burden,
      and poor patient mastery. Dyad symptoms of anxiety/depression were significantly
      associated with greater patient fatigue. CONCLUSION: Symptoms of anxiety and
      depression in COPD patients and carers are significantly associated. Given their
      high prevalence, considerable impact on mortality, impact on quality of life and
      health care use, and associations with each other, screening for and addressing
      patient and carer anxiety and depression in advanced COPD is recommended.

PMID- 29033563
TI  - Role of inspiratory capacity on dyspnea evaluation in COPD with or without
      emphysematous lesions: a pilot study.
AB  - BACKGROUND: Since forced expiratory volume in 1 second (FEV1) shows a weak
      correlation with patients' symptoms in COPD, some volume parameters may better
      reflect the change in dyspnea symptoms after treatment. In this article, we
      investigated the role of inspiratory capacity (IC) on dyspnea evaluation among
      COPD patients with or without emphysematous lesions. METHODS: In this prospective
      study, 124 patients with stable COPD were recruited. During the baseline visit,
      patients performed pulmonary function tests and dyspnea evaluation using the
      modified Medical Research Council (mMRC) scale. Partial patients underwent
      quantitative computerized tomography scans under physicians' recommendations, and
      emphysematous changes were assessed using the emphysema index (EI; low
      attenuation area [LAA]% -950). These subjects were then divided into the
      emphysema-predominant group (LAA% -950>=9.9%) and the non-emphysema-predominant
      group (LAA% -950<9.9%). After treatment for ~1 month, subjects returned for
      reevaluation of both pulmonary function parameters and dyspnea severity.
      Correlation analysis between the change in IC (DeltaIC) and dyspnea (DeltamMRC)
      was performed. RESULTS: Correlation analysis revealed that DeltaIC was negatively
      correlated with DeltamMRC (correlation coefficient [cc], -0.490, P<0.001) in the
      total study population, which was stronger than that between DeltaFEV1 and
      DeltamMRC (cc, -0.305, P=0.001). Patients with absolute DeltamMRC >1 were more
      likely to exhibit a marked increase in IC (>=300 mL) than those with absolute
      DeltamMRC <=1 (74.36% versus 35.29%; odds ratio [OR], 5.317; P<0.001). In the
      emphysema-predominant group, only DeltaIC strongly correlated with DeltamMRC (cc,
      -0.459, P=0.005), while DeltaFEV1 did not (P>0.05). CONCLUSION: IC could serve as
      an effective complement to FEV1 in COPD patients undergoing dyspnea evaluation
      after treatment. For COPD patients with predominant emphysematous lesions, an
      increase in IC is particularly more suitable for explaining dyspnea relief than
      FEV1.

PMID- 29033564
TI  - Delivery of sodium morrhuate to hemangioma endothelial cells using
      immunoliposomes conjugated with anti-VEGFR2/KDR antibody.
AB  - Hemangioma is a common benign tumor affecting infants. In this study, we prepared
      sodium morrhuate immunoliposomes through encapsulation of sodium morrhuate with
      liposomes coupled with an anti-VEGFR2/KDR antibody and examined its effect on the
      biology of human hemangioma endothelial cells (HECs). It was found that compared
      to the liposomal sodium morrhuate group, treatment with sodium morrhuate
      immunoliposomes facilitated cell detachment and apoptotic death. Confocal
      microscopy analysis revealed that sodium morrhuate immunoliposomes had a higher
      binding activity to HECs than liposomal sodium morrhuate. Apoptosis analysis
      further demonstrated that treatment with liposomal sodium morrhuate or sodium
      morrhuate immunoliposomes significantly induced apoptosis in HECs, compared to
      the control group. Western blot analysis revealed an induction of caspase-3 and
      caspase-9 levels and reduction of caspase-8 and Bcl-2 levels in HECs treated with
      liposomal sodium morrhuate or sodium morrhuate immunoliposomes. Taken together,
      these results indicate that sodium morrhuate immunoliposomes have an increased
      capacity to target HECs and promote mitochondrial apoptosis. Therefore, sodium
      morrhuate immunoliposomes may represent a promising agent in the treatment of
      hemangiomas.

PMID- 29033565
TI  - Double-receptor-targeting multifunctional iron oxide nanoparticles drug delivery
      system for the treatment and imaging of prostate cancer.
AB  - As an alternative therapeutic treatment to reduce or eliminate the current side
      effects associated with advanced prostate cancer (PCa) chemotherapy, a
      multifunctional double-receptor-targeting iron oxide nanoparticles (IONPs)
      (luteinizing hormone-releasing hormone receptor [LHRH-R] peptide- and urokinase
      type plasminogen activator receptor [uPAR] peptide-targeted iron oxide
      nanoparticles, LHRH-AE105-IONPs) drug delivery system was developed. Two tumor
      targeting peptides guided this double-receptor-targeting nanoscale drug delivery
      system. These peptides targeted the LHRH-R and the uPAR on PCa cells. Dynamic
      light scattering showed an increase in the hydrodynamic size of the LHRH-AE105
      IONPs in comparison to the non-targeted iron oxide nanoparticles (NT-IONPs).
      Surface analysis showed that there was a decrease in the zeta potential values
      for drug-loaded LHRH-AE105-IONPs compared to the NT-IONPs. Prussian blue staining
      demonstrated that the LHRH-AE105-IONPs were internalized efficiently by the human
      PCa cell line, PC-3. In vitro, magnetic resonance imaging (MRI) results confirmed
      the preferential binding and accumulation of LHRH-AE105-IONPs in PC-3 cells
      compared to normal prostate epithelial cells (RC77N/E). The results also showed
      that LHRH-AE105-IONPs significantly maintained T2 MRI contrast effects and
      reduced T2 values upon internalization by PC-3 cells. These paclitaxel-loaded
      double-receptor-targeting IONPs also showed an approximately twofold reduction in
      PC-3 cell viability compared to NT-IONPs.

PMID- 29033566
TI  - rAAV-mediated overexpression of TGF-beta via vector delivery in polymeric
      micelles stimulates the biological and reparative activities of human articular
      chondrocytes in vitro and in a human osteochondral defect model.
AB  - Recombinant adeno-associated virus (rAAV) vectors are clinically adapted vectors
      to durably treat human osteoarthritis (OA). Controlled delivery of rAAV vectors
      via polymeric micelles was reported to enhance the temporal and spatial
      presentation of the vectors into their targets. Here, we tested the feasibility
      of delivering rAAV vectors via poly (ethylene oxide) (PEO) and poly (propylene
      oxide) (PPO) (poloxamer and poloxamine) polymeric micelles as a means to
      overexpress the therapeutic factor transforming growth factor-beta (TGF-beta) in
      human OA chondrocytes and in experimental human osteochondral defects.
      Application of rAAV-human transforming growth factor-beta using such micelles
      increased the levels of TGF-beta transgene expression compared with free vector
      treatment. Overexpression of TGF-beta with these systems resulted in higher
      proteoglycan deposition and increased cell numbers in OA chondrocytes. In
      osteochondral defect cultures, a higher deposition of type-II collagen and
      reduced hypertrophic events were noted. Delivery of therapeutic rAAV vectors via
      PEO-PPO-PEO micelles may provide potential tools to remodel human OA cartilage.

PMID- 29033567
TI  - Nanoparticles for the treatment of liver fibrosis.
AB  - Chronic liver diseases represent a global health problem due to their high
      prevalence worldwide and the limited available curative treatment options. They
      can result from various causes, both infectious and noninfectious diseases. The
      application of nanoparticle (NP) systems has emerged as a rapidly evolving area
      of interest for the safe delivery of various drugs and nucleic acids for chronic
      liver diseases. This review presents the pathogenesis, diagnosis and the emerging
      nanoparticulate systems used in the treatment of chronic liver diseases caused by
      liver fibrosis. Activated hepatic stellate cell (HSC) is considered to be the
      main mechanism for liver fibrosis. Ultrasonography and magnetic resonance imaging
      techniques are widely used noninvasive diagnostic methods for hepatic fibrosis. A
      variety of nanoparticulate systems are mainly focused on targeting HSC in the
      treatment of hepatic fibrosis. As early liver fibrosis is reversible by current
      NP therapy, it is being studied in preclinical as well as clinical trials. Among
      various nanoparticulate systems, inorganic NPs, liposomes and nanomicelles have
      been widely studied due to their distinct properties to deliver drugs as well as
      other therapeutic moieties. Liposomal NPs in clinical trials is considered to be
      a milestone in the treatment of hepatic fibrosis. Currently, NP therapy for liver
      fibrosis is updating fast, and hopefully, it can be the future remedy for liver
      fibrosis.

PMID- 29033569
TI  - Associations among depression severity, painful physical symptoms, and social and
      occupational functioning impairment in patients with major depressive disorder: a
      3-month, prospective, observational study.
AB  - PURPOSE: To investigate associations among depression severity, painful physical
      symptoms (PPS), and social and occupational functioning impairment in patients
      with major depressive disorder (MDD) who had achieved complete remission (CR) or
      partial remission (PR) after acute treatment. PATIENTS AND METHODS: This was a 12
      week, multicenter, prospective, observational study. Patients with MDD treated
      with an antidepressant medication for the previous 12 weeks (+/-3 weeks) who had
      achieved CR (defined as a 17-item Hamilton Rating Scale for Depression [HAM-D17]
      score <=7) or PR (HAM-D17 score >=8 and <=18) were enrolled. Depression severity,
      PPS, and impairment in social and occupational functioning were assessed using
      the HAM-D17, the Brief Pain Inventory (Short Form) (BPI-SF), and the Social and
      Occupational Functioning Assessment Scale (SOFAS), respectively, at enrollment
      (Week 12) and after 12 weeks (Week 24). RESULTS: Overall, 323 Japanese patients
      with MDD were enrolled (CR n=158, PR n=165) and 288 patients completed the study
      (CR n=139, PR n=149). HAM-D17 and SOFAS scores were strongly and negatively
      correlated at enrollment (Week 12; P<0.0001) and Week 24 (P<0.0001). A weak
      negative correlation between the BPI-SF and SOFAS was observed at Week 24
      (P=0.0011), but not at enrollment (P=0.164). Remission status at enrollment (CR
      or PR) was associated with achieving normal social and occupational functioning
      (SOFAS score >=80) at Week 24 in patients who had not achieved normal social and
      occupational functioning (SOFAS score <80) at enrollment (CR vs PR, OR=0.05 [95%
      CIs 0.01-0.18], P<0.0001). A greater proportion of patients with CR and no PPS at
      enrollment achieved SOFAS scores >=80 at Week 24 than those with CR and PPS.
      CONCLUSION: Our results suggest that treating both depressive symptoms and PPS is
      important for achieving a normal level of functioning on a long-term basis in
      patients with MDD.

PMID- 29033568
TI  - In vivo evaluation of cetuximab-conjugated poly(gamma-glutamic acid)-docetaxel
      nanomedicines in EGFR-overexpressing gastric cancer xenografts.
AB  - Epidermal growth factor receptor (EGFR), upregulated in gastric cancer patients,
      is an oncogene of interest in the development of targeted cancer nanomedicines.
      This study demonstrates in silico modeling of monoclonal antibody cetuximab (CET
      MAb)-conjugated docetaxel (DOCT)-loaded poly(gamma-glutamic acid) (gamma-PGA)
      nanoparticles (Nps) and evaluates the in vitro/in vivo effects on EGFR
      overexpressing gastric cancer cells (MKN-28). Nontargeted DOCT-gamma-PGA Nps (NT
      Nps: 110+/-40 nm) and targeted CET MAb-DOCT-gamma-PGA Nps (T Nps: 200+/-20 nm)
      were prepared using ionic gelation followed by 1-Ethyl-3-(3-dimethyl
      aminopropyl)carbodiimide-N-Hydoxysuccinimide (EDC-NSH) chemistry. Increased
      uptake correlated with enhanced cytotoxicity induced by targeted Nps to EGFR +ve
      MKN-28 compared with nontargeted Nps as evident from MTT and flow cytometric
      assays. Nanoformulated DOCT showed a superior pharmacokinetic profile to that of
      free DOCT in Swiss albino mice, indicating the possibility of improved
      therapeutic effect in the disease model. Qualitative in vivo imaging showed early
      and enhanced tumor targeted accumulation of CET MAb-DOCT-gamma-PGA Nps in EGFR
      +ve MKN-28-based gastric cancer xenograft, which exhibited efficient arrest of
      tumor growth compared with nontargeted Nps and free DOCT. Thus, actively targeted
      CET MAb-DOCT-gamma-PGA Nps could be developed as a substitute to conventional
      nonspecific chemotherapy, and hence could become a feasible strategy for cancer
      therapy for EGFR-overexpressing gastric tumors.

PMID- 29033570
TI  - Atypical depression: current perspectives.
AB  - The history and present status of the definition, prevalence, neurobiology, and
      treatment of atypical depression (AD) is presented. The concept of AD has evolved
      through the years, and currently, in Diagnostic and Statistical Manual of Mental
      Disorders (DSM), Fifth Edition, the specifier of depressive episode with atypical
      feature is present for both diagnostic groups, that is, depressive disorders and
      bipolar and related disorders. This specifier includes mood reactivity,
      hyperphagia, hypersomnia, leaden paralysis, and interpersonal rejection
      sensitivity. Prevalence rates of AD are variable, depending on the criteria,
      methodology, and settings. The results of epidemiological studies using DSM
      criteria suggest that 15%-29% of depressed patients have AD, and the results of
      clinical studies point to a prevalence of 18%-36%. A relationship of AD with
      bipolar depression, seasonal depression, and obesity has also been postulated.
      Pathogenic research has been mostly focused on distinguishing AD from melancholic
      depression. The differences have been found in biochemical studies in the areas
      of hypothalamic-pituitary-adrenal axis, inflammatory markers, and the leptin
      system, although the results obtained are frequently controversial. A number of
      findings concerning such differences have also been obtained using neuroimaging
      and neurophysiological and neuropsychological methods. An initial concept of AD
      as a preferentially monoamine oxidase inhibitor-responsive depression, although
      confirmed in some further studies, is of limited use nowadays. Currently, despite
      numerous drug trials, there are no comprehensive treatment guidelines for AD. We
      finalize the article by describing the future research perspectives for the
      definition, neurobiology, and treatment. A better specification of diagnostic
      criteria and description of clinical picture, a genome-wide association study of
      AD, and establishing updated treatment recommendations for this clinical
      phenomenon should be the priorities for the coming years.

PMID- 29033571
TI  - Bronchial thermoplasty and the role of airway smooth muscle: are we on the right
      direction?
AB  - Asthma is characterized by inflammation of the airways that includes eosinophils,
      basal membrane thickening, epithelial sloughing, vascular changes, smooth muscle
      hypertrophy and hyperplasia, and mucous gland hyperplasia. Recently, there have
      been studies on the role of hypersensitivity and inflammation in asthma, but the
      role of bronchial smooth muscle remains unclear. Bronchial thermoplasty is an
      endoscopic procedure that is approved by the US Food and Drug Administration
      (FDA) for the treatment of severe refractory asthma, based on the local delivery
      of radio frequency at 65 degrees C to the airways, with the aim of controlling
      bronchospasm through a reduction of airway smooth muscle (ASM). Several recent
      studies have shown significant improvement in clinical outcomes of bronchial
      thermoplasty for asthma, including symptom control, reduction in exacerbation and
      hospitalization rates, improved quality of life, and reduction in number of
      working days or school days lost due to asthma. Data from these recent studies
      have shown reduction in ASM following bronchial thermoplasty and changes in
      inflammation patterns. It has also been argued that bronchial thermoplasty may
      have modulating effects on neuroendocrine epithelial cells, bronchial nerve
      endings, TRPV1 nerve receptors, and type-C unmyelinated fibers in the bronchial
      mucosa. This may involve interrupting the central and local reflexes responsible
      for the activation of bronchospasm in the presence of bronchial hyperreactivity.
      Several questions remain regarding the use of bronchial thermoplasty, mechanism
      of action, selection of appropriate patients, and long-term effects. In this
      review, the role of ASM in the pathogenesis of asthma and the key aspects of
      bronchial thermoplasty are discussed, with a focus on the potential clinical
      effects of this promising procedure, beyond the reduction in ASM.

PMID- 29033572
TI  - Role of heart-rate variability in preoperative assessment of physiological
      reserves in patients undergoing major abdominal surgery.
AB  - BACKGROUND: Major abdominal surgery (MAS) is associated with increased morbidity
      and mortality. The main objective of our study was to evaluate the predictive
      value of heart-rate variability (HRV) concerning development of postoperative
      complications in patients undergoing MAS. The secondary objectives were to
      identify the relationship of HRV and use of vasoactive drugs during anesthesia,
      intensive care unit length of stay (ICU-LOS), and hospital length of stay (H
      LOS). PATIENTS AND METHODS: Sixty-five patients scheduled for elective MAS were
      enrolled in a prospective, single-center, observational study. HRV was measured
      by spectral analysis (SA) preoperatively during orthostatic load. Patients were
      divided according to cardiac autonomic reactivity (CAR; n=23) and non-cardiac
      autonomic reactivity (NCAR; n=30). RESULTS: The final analysis included 53
      patients. No significant difference was observed between the two groups regarding
      type of surgery, use of minimally invasive techniques or epidural catheter,
      duration of surgery and anesthesia, or the amount of fluid administered
      intraoperatively. The NCAR group had significantly greater intraoperative blood
      loss than the CAR group (541.7+/-541.9 mL vs 269.6+/-174.3 mL, p<0.05). In the
      NCAR group, vasoactive drugs were used during anesthesia more frequently (n=21 vs
      n=4; p<0.001), and more patients had at least one postoperative complication
      compared to the CAR group (n=19 vs n=4; p<0.01). Furthermore, the NCAR group had
      more serious complications (Clavien-Dindo >= Grade III n=6 vs n=0; p<0.05) and a
      greater number of complications than the CAR group (n=57 vs n=5; p<0.001).
      Significant differences were found for two specific subgroups of complications:
      hypotension requiring vasoactive drugs (NCAR: n=10 vs CAR: n=0; p<0.01) and ileus
      (NCAR: n=11 vs CAR: n=2; p<0.05). Moreover, significant differences were found in
      the ICU-LOS (NCAR: 5.7+/-3.5 days vs CAR: 2.6+/-0.7 days; p<0.0001) and H-LOS
      (NCAR: 12.2+/-5.6 days vs CAR: 7.2+/-1.7 days; p<0.0001). CONCLUSION:
      Preoperative HRV assessment during orthostatic load is objective and useful for
      identifying patients with low autonomic physiological reserves and high risk of
      poor post-operative course.

PMID- 29033573
TI  - Ten-year outcome of intraoperative treatment of atrial fibrillation using
      radiofrequency ablation.
AB  - BACKGROUND: Intraoperative radiofrequency ablation (RFA) has been advocated to
      treat atrial fibrillation (AF). This report examines the long-term effects of
      intraoperative RFA in the prevention of recurrence of AF when used as an
      adjunctive treatment in patients undergoing cardiac procedures for primary
      indications unrelated to their arrhythmia. METHODS: The study reviewed the
      records of patients from a tertiary medical center which had 2 cardiac surgeons
      performing an intraoperative adjunctive RFA procedure. A total of 20 patients
      undergoing RFA between April 11, 2003 and May 10, 2005 were included and followed
      for up to 10 years. The primary effectiveness outcome of the study was the
      recurrence of AF during the follow-up period. Data were collected from office or
      hospital medical records. RESULTS: A total of 20 patients were included (mean age
      69.4 years, males 40%). Eight patients were followed for 10 years and 2 patients
      for 9 years; 7 patients died during the 10-year follow-up period and 3 patients
      were lost to follow-up. As their primary procedures, the patients underwent valve
      surgery (65%), bypass surgery (15%), or both (20%). Intraoperative RFA failed to
      restore sinus rhythm in 2 patients. In the remaining 18 patients, AF recurred in
      10 patients within 2 months of surgery, in 1 patient at 5 months, in 1 patient at
      7 months, and in 6 patients after 1 year. CONCLUSION: AF had recurred in 100% of
      patients by the end of the long-term follow-up period. The adjunctive
      intraoperative RFA and postoperative interventions employed in this early study
      failed to maintain sinus rhythm.

PMID- 29033574
TI  - Surgical site infections following instrumented stabilization of the spine.
AB  - BACKGROUND: Implant-associated infections are still a feared complication in the
      field of orthopedics. Bacteria attach to the implant surface and form so-called
      biofilm colonies that are often difficult to diagnose and treat. Since the
      majority of studies focus on prosthetic joint infections (PJIs) of the hip and
      knee, current treatment options (eg, antibiotic prophylaxis) of implant
      associated infections have mostly been adapted according to these results.
      OBJECTIVE: The aim of this study was to evaluate patients with surgical site
      infections following instrumented stabilization of the spine with regard to
      detected bacteria species and the course of the disease. PATIENTS AND METHODS: We
      performed a retrospective single-center analysis of implant-associated infections
      of the spine from 2010 to 2014. A total of 138 patients were included in the
      study. The following parameters were evaluated: C-reactive protein serum
      concentration, microbiological evaluation of tissue samples, the time course of
      the disease, indication for instrumented stabilization of the spine, localization
      of the infection, and the number of revision surgeries required until cessation
      of symptoms. RESULTS: Coagulase-negative Staphylococcus spp. were most commonly
      detected (n=69, 50%), followed by fecal bacteria (n=46, 33.3%). In 23.2% of
      cases, no bacteria were detected despite clinical suspicion of an infection. Most
      patients suffered from degenerative spine disorders (44.9%), followed by spinal
      fractures (23.9%), non-degenerative scoliosis (20.3%), and spinal tumors (10.1%).
      Surgical site infections occurred predominantly within 3 months (64.5%), late
      infections after 2 years were rare (4.3%), in particular when compared with PJIs.
      Most cases were successfully treated after 1 revision surgery (60.9%), but there
      were significant differences between bacteria species. Fecal bacteria were more
      difficult to treat and often required more than 1 revision surgery. CONCLUSION:
      In summary, we were able to demonstrate significant differences between spinal
      implant-associated infections and PJIs. These aspects should be considered early
      on in the treatment of surgical site infections following instrumented
      stabilization of the spine.

PMID- 29033575
TI  - Renal safety of tenofovir and/or entecavir in patients with chronic HBV
      monoinfection.
AB  - BACKGROUND: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are
      recommended as the first-line therapy for chronic hepatitis B (CHB) due to their
      genetic barrier to resistance and effectiveness of virological suppression. TDF
      and ETV may cause renal toxicity through various mechanisms such as renal tubular
      injury, apoptosis, and mitochondrial toxicity. The aims of the current review
      were to assess the potential renal toxicity associated with the use of TDF and
      ETV in patients infected with chronic hepatitis B virus (HBV) and to provide
      clinical perspectives on these two agents in the treatment of CHB. METHODS: A
      literature search of clinical studies published in PubMed and posted on
      ClinicalTrials.gov website was implemented to find studies evaluating the
      potential renal toxicity of TDF and ETV. RESULTS: Twenty-one studies were
      examined in this review. The TDF dose used in the studies was 245 or 300 mg/day
      and that of ETV was 0.5 or 1 mg/day. Based on the markers of renal function,
      patients treated with TDF were not more likely to show changes in renal function
      than those treated with ETV; however, the estimated glomerular filtration rates
      (eGFRs) of patients receiving TDF tended to be more clearly reduced than those of
      patients receiving ETV. The eGFRs of patients treated with TDF decreased in a
      time-dependent manner, whereas those of patients treated with ETV increased or
      decreased across various time points. CONCLUSION: The data shown in this study
      suggest that use of TDF and ETV could be at least associated with reductions in
      renal function in patients with chronic HBV infection. However, various risk
      factors, such as pre-existing renal failure and comorbidities, are also
      associated with decreased renal function during the treatment of TDF and ETV.
      Thus, studies of management strategies for HBV-infected patients with these risk
      factors are necessary in the near future.

PMID- 29033576
TI  - Lumbar spinal stenosis attributable to tophaceous gout: case report and review of
      the literature.
AB  - OBJECTIVES: Tophaceous gout seldom affects the axial skeleton. Symptoms vary
      according to the differential localization of urate deposits and the diagnosis is
      often delayed. Here, we report an unusual case of lumbar spinal stenosis caused
      by extradural tophaceous deposits. METHODS: We retrospectively reviewed a case of
      a patient with tophaceous gout of the lumbar spine and reviewed the relevant
      literature. RESULTS: A 62-year-old man with a 2-year history of lower back pain
      and a 3-month history of lower limb radiation pain and intermittent claudication
      was admitted. After laboratory and imaging investigations he underwent surgical
      decompression and stabilization. Histological analysis of the extracted specimen
      confirmed that it was gouty tophus. The patient's symptoms improved progressively
      after the operation. He recovered very well with no complications. CONCLUSION:
      The mechanism associated with axial gout is not yet clear. Obesity, inactivity,
      and previous degenerative disc disease may be the risk factors for spinal tophus.
      The clinical symptoms are diverse according to the differential localization of
      urate deposits. It is not easy to diagnose this disease radiographically by
      routine radiological examination. Analysis of a biopsy specimen is definitely the
      only way to confirm diagnosis. Surgical treatment should be considered in
      patients with spinal gout who are experiencing neurological deterioration.

PMID- 29033577
TI  - Are adipocytokines inflammatory or metabolic mediators in patients with
      inflammatory bowel disease?
AB  - This study examined the adiponectin and leptin levels and insulin resistance (IR)
      in patients with inflammatory bowel disease (IBD) and the associations between
      these factors and IBD characteristics. Fasting serum leptin, adiponectin,
      glucose, and insulin levels, as well as inflammatory parameters, were measured in
      105 patients with IBD (49 patients with Crohn's disease [CD], 56 patients with
      ulcerative colitis [UC]) and 98 healthy controls [HC]. IR was evaluated using the
      Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Disease activity
      and severity in patients with UC were evaluated using the Truelove-Witts index,
      and patients with CD were evaluated using the Crohn's Disease Activity Index.
      Serum adiponectin levels were found to be significantly lower in patients with CD
      and UC (p<0.001). Serum leptin levels were also found to be significantly higher
      in both the UC and CD groups (p<0.001). When HOMA-IR levels were compared, no
      significant difference was detected for either the CD or UC groups compared with
      the controls. In conclusion, it was shown that leptin levels increased and
      adiponectin levels decreased in patients with IBD, which is thought to be related
      to chronic inflammation. The effects of adipocytokines in patients with IBD with
      inflammatory and metabolic processes need to be investigated in further broader
      studies.

PMID- 29033578
TI  - Right ventricular systolic function in hypertensive heart failure.
AB  - BACKGROUND: Heart failure (HF) is a major cause of cardiovascular admissions and
      hypertensive heart failure (HHF) is the most common cause of HF admissions in sub
      Saharan Africa, Nigeria inclusive. Right ventricular (RV) dysfunction is being
      increasingly recognized in HF and found to be an independent predictor of adverse
      outcomes in HF. This study aimed to determine the prevalence of RV systolic
      dysfunction in HHF by several echocardiographic parameters. METHODOLOGY: One
      hundred subjects with HHF were recruited consecutively into the study along with
      50 age and sex-matched controls. All study participants gave written informed
      consent, and had a full physical examination, blood investigations, 12-lead
      electrocardiogram, and transthoracic echocardiography. RV systolic function was
      assessed in all subjects using different methods based on the American Society of
      Echocardiography guidelines for echocardiographic assessment of the right heart
      in adults. This included tricuspid annular plane systolic excursion (TAPSE), RV
      myocardial performance index (MPI), and RV systolic excursion velocity by tissue
      Doppler (S'). RESULTS: RV systolic dysfunction was found in 53% of subjects with
      HHF by TAPSE, 56% by RV MPI, and 48% by tissue Doppler systolic excursion S'. RV
      systolic dysfunction increased with reducing left ventricular ejection fraction
      (LVEF) in subjects with HHF. CONCLUSION: A high proportion of subjects with HHF
      were found to have RV systolic functional abnormalities using TAPSE, RV MPI, and
      RV S'. Prevalence of RV systolic dysfunction increased with reducing LVEF.

PMID- 29033579
TI  - General practitioners' and primary care nurses' care for people with
      disabilities: quality of communication and awareness of supportive services.
AB  - BACKGROUND: General practitioners (GPs) and primary-care nurses (PCNs) often feel
      inexperienced or inadequately educated to address unmet needs of people with
      disabilities (PDs). In this research, GPs' and PCNs' communication with PDs and
      health care professionals, as well as their awareness of supportive measures
      relevant to PDs (sensory disabilities excluded), was examined. MATERIALS AND
      METHODS: An electronic questionnaire was sent out to 545 GPs and 1,547 PCNs
      employed in Limburg (Belgium). GPs and PCNs self-reported about both
      communication with parties involved in care for PDs (scale very good, good, bad,
      very bad) and their level of awareness of supportive measures relevant for PDs
      (scale unaware, inadequately aware, adequately aware). RESULTS: Of the
      questionnaire recipients, 6.6% (36 of 545) of GPs and 37.6% (588 of 1,547) of
      PCNs participated: 68.8% of 32 GPs and 45.8% of 443 PCNs categorized themselves
      as communicating well with PDs, and attributed miscommunication to limited
      intellectual capacities of PDs. GPs and PCNs reported communicating well with
      other health care professionals. Inadequate awareness was reported for tools to
      communicate (88.3% of GPs, 89% of PCNs) and benefits for PDs (44.1% of GPs, 66.9%
      of PCNs). CONCLUSION: GPs' and PCNs' lacking awareness of communication aids is
      problematic. Involvement in a multidisciplinary, expert network might bypass
      inadequate awareness of practical and social support measures.

PMID- 29033581
TI  - NANOG as an adverse predictive marker in advanced non-small cell lung cancer
      treated with platinum-based chemotherapy.
AB  - PURPOSE: NANOG is a master transcription factor that regulates stem cell
      pluripotency and cellular reprograming. Increased NANOG expression has been
      associated with poor survival in several human malignancies. However, the
      clinical significance of NANOG overexpression in lung cancer has been scarcely
      evaluated. The aim of this study was to investigate whether NANOG levels are
      associated with clinical outcomes of patients with non-small cell lung cancer
      (NSCLC) who were treated with platinum-based chemotherapy. METHODS: NANOG levels
      were evaluated immunohistochemically using the histologic score (H-score) in
      tumor tissues from patients with advanced NSCLC who received platinum-based
      doublet treatment. We performed survival analyses according to the NANOG levels
      and evaluated the association between clinicopathological parameters and levels
      of NANOG. RESULTS: Multivariate analyses using 112 tumor specimens showed that
      high NANOG levels were independently associated with short progression-free
      survival (hazard ratio [HR] =3.09, 95% confidence interval [CI]: 2.01-4.76) and
      with short overall survival (HR =3.00, 95% CI: 1.98-4.54). Similar results were
      shown in the subgroup analyses for patients with adenocarcinoma and squamous cell
      carcinoma. NANOG expression was not associated with any clinicopathological
      parameter such as age, gender, smoking status, stage, differentiation, or
      histological subtypes. CONCLUSION: NANOG overexpression was associated with poor
      response and short overall survival in patients with advanced NSCLC who were
      treated with platinum-based chemotherapy, suggesting that NANOG could be a
      potential adverse predictive marker in this setting.

PMID- 29033580
TI  - The influence of vascular endothelial growth factor-A and matrix
      metalloproteinase-2 and -9 in angiogenesis, metastasis, and prognosis of
      endometrial cancer.
AB  - Angiogenesis (the growth of new blood vessels) is essential in most of the body's
      physiological processes, such as in the normal functioning of the endometrium
      during and after the menstrual cycle. Vascular endothelial growth factor (VEGF)
      and matrix metalloproteinase (MMP) are the mostly expressed angiogenic factors,
      especially, during the process of endometrial degeneration and remodeling. In
      carcinogenesis, tumor hypoxia-induced factors, through the process of "angiogenic
      switch", stimulate the production of angiogenic factors, particularly VEGF and
      MMP. Subsequently, these angiogenic factors are associated with degradation,
      differentiation, proliferation, and migration of vascular endothelial cells,
      enhancing the formation of new blood vessels to supply the tumor with oxygen and
      nutrients. This process is equally significant for tumor development and
      metastasis. Hence, like in other cancers, the overexpression of MMP and VEGF in
      endometrial cancer (EC) seems to play a significant role in its tumorigenesis and
      metastasis. This research will discuss the influence of MMP and VEGF on
      angiogenesis, metastasis, and the prognosis of EC as well as the clinical
      importance of the factors in the diagnosis of EC.

PMID- 29033582
TI  - HIF pathway and c-Myc as biomarkers for response to sunitinib in metastatic clear
      cell renal cell carcinoma.
AB  - BACKGROUND: Clear-cell renal cell carcinoma (ccRCC) is a heterogeneous disease
      with a different clinical behavior and response to targeted therapies.
      Differences in hypoxia-inducible factor (HIF) expression have been used to
      classify von Hippel-Lindau gene (VHL)-deficient ccRCC tumors. c-Myc may be
      driving proliferation in HIF-2alpha-expressing tumors in a growth factor
      independent manner. OBJECTIVE: To explore the HIF-1alpha, HIF-2alpha and c-Myc
      baseline expression as potential predictors of sunitinib outcome as well as the
      effectiveness and safety with sunitinib in patients with metastatic ccRCC in
      routine clinical practice. METHODS: This was an observational and prospective
      study involving 10 Spanish hospitals. Formalin-fixed, paraffin-embedded primary
      tumor samples from metastatic ccRCC patients who received sunitinib as first-line
      treatment were analyzed. Association between biomarker expression and sunitinib
      treatment outcomes was evaluated. Kaplan-Meier method was applied to measure
      progression-free survival (PFS) and overall survival. RESULTS: Eighty-one
      patients were included: median PFS was 10.8 months (95% CI: 7.4-13.5 months),
      median overall survival was 21.8 months (95% CI: 14.7-29.8 months) and objective
      response rate was 40.7%, with 7.4% of patients achieving a complete response.
      Molecular marker staining was performed in the 69 available tumor samples.
      Significant association with lower PFS was identified for double c-Myc/HIF-2alpha
      positive staining tumors (median 4.3 vs 11.5 months, hazard ratio =2.64, 95% CI:
      1.03-6.80, P=0.036). A trend toward a lower PFS was found in positive c-Myc
      tumors (median 5.9 vs 10.9 months, P=0.263). HIF-1alpha and HIF-2alpha expression
      levels were not associated with clinical outcome. CONCLUSION: These preliminary
      results suggest that predictive subgroups might be defined based on biomarkers
      such as c-Myc/HIF-2alpha. Further validation with more patients will be needed in
      order to confirm it. Outcomes with sunitinib in metastatic ccRCC in daily
      clinical practice resemble those obtained in clinical trials.

PMID- 29033583
TI  - The effects of nonsteroidal anti-inflammatory drugs in the incident and recurrent
      risk of hepatocellular carcinoma: a meta-analysis.
AB  - BACKGROUND: Recent studies have showed that nonsteroidal anti-inflammatory drugs
      (NSAIDs) could reduce the risk of several types of cancer. However,
      epidemiological evidence of the association between NSAIDs intake and the risk of
      hepatocellular carcinoma (HCC) remains controversial. METHODS: To assess the
      preventive benefit of NSAIDs in HCC, we simultaneously searched the databases of
      PubMed, EmBase, Web of Science, and Scopus and screened eligible publications.
      RESULTS: A total of twelve articles (published from 2000 to 2017) from five
      countries were identified by retrieval. We observed a significantly lower risk of
      HCC incidence among users of NSAIDs than among those who did not use NSAIDs
      (pooled hazard ratio [HR] value =0.81, 95% confidence interval [CI]: 0.69-0.94).
      No evidence of publication bias was observed (Begg's test, P=0.755; Egger's test,
      P=0.564). However, when stratified according to the categories of NSAIDs, users
      of non-aspirin NSAIDs (HR =0.81, 95% CI: 0.70-0.94), but not aspirin (HR =0.77,
      95% CI: 0.58-1.02), showed a statistically significant reduced HCC incidence. We
      also found that NSAIDs use significantly reduced the recurrent risk of HCC, with
      a HR value of 0.79 (95% CI: 0.75-0.84), whereas there was no statistically
      significant association between NSAIDs use and HCC mortality, with a HR value
      0.65 (95% CI: 0.40-1.06). CONCLUSION: Taken together, our meta-analysis
      demonstrates that NSAIDs significantly reduce the incident and recurrent risk of
      HCC.

PMID- 29033584
TI  - DNA ploidy and S-phase fraction analysis in peritoneal carcinomatosis from
      ovarian cancer: correlation with clinical pathological factors and response to
      chemotherapy.
AB  - OBJECTIVE: We investigated the correlation between ploidy or S-phase fraction
      (SPF) and the clinical pathological characteristics of patients with peritoneal
      carcinomatosis from ovarian cancer. We also assessed their relation with the in
      vivo and in vitro response to several chemotherapeutic agents. PATIENTS AND
      METHODS: Fifty-three patients with peritoneal carcinomatosis from ovarian cancer
      were enrolled. Frozen tumor tissue was dissociated by a detergent-trypsin method,
      and the resulting cell suspension was stained with RNase A and propidium iodide.
      Samples were then analyzed for ploidy and SPF by flow cytometry. Fresh tumor
      tissue was dissociated by enzymatic digestion, and cells were exposed to
      different concentrations of cisplatin, adriamycin, carboplatin, gemcitabine and
      taxol for 72 hours. In vitro drug sensitivity was then measured using the
      sulforhodamine B assay. RESULTS: No significant correlation was found between
      ploidy or SPF and patient characteristics, even though primary carcinomas were
      mainly hyperdiploid and more proliferative than recurrent tumors. SPF differed
      significantly among ploidy categories (P=0.01), and high SPF was associated with
      short-term survival (P=0.48). Patients with multiploid tumors were the most
      resistant to platinum-based chemotherapy, whereas those with hyperdiploid tumors
      were the most responsive. In vitro multiploid tumors were the least sensitive,
      while hypodiploid samples showed the highest sensitivity to the tested drugs.
      Sensitivity to adriamycin was significantly correlated with ploidy (P=0.03),
      whereas sensitivity to taxol was correlated with SPF (P=0.04). CONCLUSION: Our
      results indicate that ploidy and SPF could facilitate the choice of therapy for
      patients with peritoneal carcinomatosis.

PMID- 29033585
TI  - Clinical significance of SLP-2 in hepatocellular carcinoma tissues and its
      regulation in cancer cell proliferation, migration, and EMT.
AB  - Stomatin-like protein 2 (SLP-2) gene was significantly upregulated in a variety
      of tumor tissues and found to be involved in proliferation and metastasis.
      However, its functional role in hepatocellular carcinoma (HCC) remains unknown.
      Our study was to investigate the function of SLP-2 in cell proliferation,
      migration, invasion, cell apoptosis, and the process of epithelial-mesenchymal
      transition (EMT) in HCC. SLP-2 mRNA and protein expression in HCC were assessed
      by qRT-PCR and immunohistochemical staining. In vitro, we determined cell
      proliferation, migration, invasion, and cell apoptosis by CCK-8, transwell, and
      flow cytometry assays, respectively. SLP-2 was found to be upregulated at both
      mRNA and protein levels in HCC tissues, and its aberrant overexpression was
      linked with poor prognosis in patients with HCC. SLP-2 downregulation by siRNAs
      significantly suppressed cell proliferation, migration, invasion, anti-apoptosis
      abilities, and inhibited EMT process in vitro. In conclusion, the present study
      demonstrated the overexpression of SLP-2 in HCC tissues for the first time. As an
      effective regulator involved in cell proliferation, migration, invasion, cell
      apoptosis, and EMT, SLP-2 could be a novel therapeutic target for patients with
      HCC who express high levels of SLP-2.

PMID- 29033587
TI  - DNA hypermethylated status and gene expression of PAX1/SOX1 in patients with
      colorectal carcinoma.
AB  - BACKGROUND: Colorectal cancer (CRC) is a widespread and aggressive carcinoma with
      poor prognosis. Hypermethylation of specific gene promoters is an important
      mechanism of CRC. In this study, we investigated the hypermethylation of paired
      boxed gene 1 (PAX1) and sex-determining region Y-related high-mobility group box
      1 (SOX1) genes in CRC tissues. METHODS: DNA methylation at cg2,09,07,471 PAX1 and
      cg0,66,75,478 SOX1 from 166 cancer tissues and 37 normal tissues from CRC
      patients were compared using datasets downloaded from The Cancer Genome Atlas.
      Quantitative methylation-specific polymerase chain reaction and assay of PAX1 and
      SOX1 were performed in dissected tumor and paracancerous tissues by surgery from
      41 CRC patients. Quantitative reverse transcription polymerase chain reaction and
      immunohistochemistry assay were performed in both CRC and paired normal tissues
      to detect mRNA and protein expression, respectively. RESULTS: Methylation levels
      of PAX1/SOX1 genes were significantly higher in cancer tissues than in paired
      normal tissues. PAX1 and SOX1 genes were methylated in 28 (68.3%) of the 41 CRC
      samples but in 5 (12.2%) and 0 (0%) of the paired normal control samples (both
      P<0.001), respectively. Sensitivities and specificities of PAX1 methylation for
      the detection of cancer were 68.3% and 87.8%, respectively, whereas the
      corresponding values for SOX1 were 68.3% and 100%. However, the Kaplan-Meier
      analysis illustrated no significant difference in the overall survivals between
      patients with high and low methylation levels of SOX1 or PAX1 (P>0.5). In
      addition, the methylation level of PAX1/SOX1 was significantly higher in CRC
      patients with high TNM stage (TNM stage III/IV, 3.11+/-2.43) than those with low
      TNM stage (TNM stage I/II, 1.26+/-2.94, P<0.05). Relative RNA and protein
      expression levels of PAX1/SOX1 were both significantly lower in CRC tissues than
      in their paired normal tissue. CONCLUSIONS: This study is the first analysis of
      the methylation of PAX1/SOX1, which may be new biomarkers for CRC screening.

PMID- 29033586
TI  - Targeting the androgen receptor in triple-negative breast cancer: current
      perspectives.
AB  - Triple-negative breast cancer (TNBC) is an aggressive subtype associated with
      frequent recurrence and metastasis. Unlike hormone receptor-positive subtypes,
      treatment of TNBC is currently limited by the lack of clinically available
      targeted therapies. Androgen signaling is necessary for normal breast
      development, and its dysregulation has been implicated in breast tumorigenesis.
      In recent years, gene expression studies have identified a subset of TNBC that is
      enriched for androgen receptor (AR) signaling. Interference with androgen
      signaling in TNBC is promising, and AR-inhibiting drugs have shown
      antitumorigenic activity in preclinical and proof of concept clinical studies.
      Recent advances in our understanding of androgenic signaling in TNBC, along with
      the identification of interacting pathways, are allowing development of the next
      generation of clinical trials with AR inhibitors. As novel AR-targeting agents
      are developed and evaluated in clinical trials, it is equally important to
      establish a robust set of biomarkers for identification of TNBC tumors that are
      most likely to respond to AR inhibition.

PMID- 29033588
TI  - HOXD-AS1 functions as an oncogenic ceRNA to promote NSCLC cell progression by
      sequestering miR-147a.
AB  - Non-small cell lung cancer (NSCLC) is one of the most common malignancies
      worldwide, and it occurs at a higher frequency in males. HOXD-AS1, an important
      cancer-associated long noncoding RNA (lncRNA), contributes to the development and
      progression of several cancers. However, the exact roles of HOXD-AS1 in NSCLC
      progression are still unknown. Here, we investigated the underlying mechanisms of
      HOXD-AS1 in human NSCLC tissues. We found that lncRNA HOXD-AS1 was specifically
      upregulated (P<0.001) in NSCLC tissues and promoted cancer cell growth by
      targeting miR-147a. Moreover, HOXD-AS1 expression positively correlated with
      NSCLC clinical pathologic characteristics (tumor size, P=0.006; tumor stage,
      P=0.044; recurrence, P=0.031) and survival rate (P=0.003). HOXD-AS1 knockdown
      reduced proliferation and promoted apoptosis of NSCLC cells. The dual-luciferase
      reporter assay showed that HOXD-AS1 could negatively regulate the expression of
      miR-147a. miR-147a inhibition abrogated the effect of HOXD-AS1 knockdown on the
      proliferation and apoptosis of NSCLC cells. Furthermore, HOXD-AS1 positively
      regulated the expression of pRB (a tumor suppressor protein) in NSCLC cells.
      Taken together, our data indicated that HOXD-AS1 might be an oncogenic lncRNA
      that promotes proliferation of NSCLC and could be a therapeutic target in NSCLC.

PMID- 29033589
TI  - Yttrium-90 radioembolization of unresectable hepatocellular carcinoma - a single
      center experience.
AB  - PURPOSE: To determine the value of radioembolization (RE) for treatment of
      unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Records of
      patients undergoing RE for unresectable HCC were retrospectively reviewed.
      Biochemical and clinical toxicities, imaging response (according to modified
      Response Evaluation Criteria In Solid Tumors), time-to-progression (TTP) and
      overall survival (OS) were analyzed. Data were stratified according to clinical
      and procedural parameters. Univariate and multivariate analyses were performed.
      RESULTS: One hundred and fifteen patients (89 male, mean age 69.3 years)
      underwent 158 REs (119 resin-, 39 glass-based) (Barcelona Clinic Liver Cancer
      [BCLC]-A: 6.1%, B: 33.9%, C: 60.0%). Median clinical follow-up was 5.9 (0.9-83.5)
      months. No grade 4 or 5 clinical toxicities were noted. Objective response rate
      was 35.6%; disease control rate was 76.7%. Median TTP of the treated part of the
      liver was 4 (0.9-45.4) months. 108/115 patients died during follow-up (median OS
      8.4 [0.3-82.8] months after first RE [BCLC-A: 52.8 months, BCLC-B: 12.4 months,
      BCLC-C: 6.1 months]). On multivariate analysis, baseline Eastern Co-operative
      Oncology Group status <1, ascites prior to RE and best imaging response were
      predictors of longer OS. In BCLC-C patients, tumor burden, ascites prior to RE,
      baseline gamma-glutamyltransferase and Child-Pugh score were predictive of OS.
      CONCLUSIONS: RE is safe and effective in carefully selected patients suffering
      from HCC with a low complication rate. Low baseline Eastern Co-operative Oncology
      Group status and absence of ascites prior to RE are positive prognostic factors.

PMID- 29033590
TI  - Sitting time and occupational and recreational physical activity in relation to
      the risk of esophageal squamous cell carcinoma.
AB  - BACKGROUNDS: Sitting time and physical activity are associated with cancer risk;
      however, their roles in the development of esophageal squamous cell carcinoma
      (ESCC) are inconclusive. This study aimed to investigate the effects of total
      sitting time, occupational activity time (OAT), and recreational activity time
      (RAT) on ESCC risk. METHODS: Five hundred fifty-seven ESCC patients and 543
      healthy controls matched by sex and age were recruited for this study.
      Conditional logistic regression was performed to obtain odds ratios (ORs) and 95%
      confidence intervals (CIs). RESULTS: Longer total sitting time (adjusted OR [AOR]
      2.54, 95% CI 1.58-4.09) and longer OAT (AOR 2.90, 95% CI 2.11-3.99) were
      associated with higher ESCC risk, while longer RAT (AOR 0.27, 95% CI 0.19-0.38)
      could reduce ESCC risk. When the body mass index was incorporated into the
      multivariable models, the results changed slightly. In risk estimation according
      to sex, the same trends were observed in both men and women. Furthermore, longer
      RAT could completely or partially diminish the impacts of longer sitting time and
      OAT on increasing ESCC risk. CONCLUSION: Long sitting time and long OAT can
      increase the risk of ESCC, while long RAT is significantly associated with
      decreased ESCC risk.

PMID- 29033591
TI  - Clinicopathological features and prognoses in younger and older patients with
      gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: Patients of different ages with gastric cancer (GC)
      have different clinicopathological features and prognoses. The results for
      different crowds are limited and controversial. The aim of this study was to
      investigate the differences in clinicopathological features and prognoses between
      younger and older GC patients. METHODS: From January 2007 to December 2011, a
      consecutive total of 112 GC patients under 41 years old and 358 GC patients over
      69 years old who underwent gastrectomy for GC were recruited for this study.
      Then, the clinicopathological features and prognoses of these patients were
      analyzed comparatively. RESULTS: The gender, differentiation, carbohydrate
      antigen (CA) 19-9 and carcinoembryonic antigen (CEA) were significantly different
      between younger and older GC patients. There were more female and
      undifferentiated younger GC patients, and there were higher percentages of
      positive CA19-9 and CEA in older GC patients. The number of metastatic lymph
      nodes was an independent risk parameter for prognosis in younger patients, and
      the AJCC TNM (Tumor-Nodes-Metastases classification by American Joint Committee
      on Cancer) stage, radicality and tumor size were independent risk parameters for
      prognosis in older GC patients. Younger GC patients have a much better prognoses
      with lower monocyte-to-lymphocyte ratio and higher prognostic nutritional index
      than older patients. CONCLUSIONS: Younger GC patients have better immunity and
      nutritional status and better prognoses. The number of metastatic lymph nodes was
      the only risk parameter for prognosis in younger GC patients. We should take more
      effective treatments for younger GC patients with lymph nodes metastasis and pay
      more attention to the nutritional problems of older GC patients.

PMID- 29033592
TI  - Is this the end of cytotoxic chemotherapy in Merkel cell carcinoma?
AB  - Although cytotoxic chemotherapy has been used often in the management of Merkel
      cell carcinoma (MCC), its benefit remains uncertain. Despite being considered a
      chemosensitive disease, the duration of response is generally short, and the
      survival benefit is unclear. With the recent FDA approval of the anti-programmed
      cell death ligand 1 (PD-L1) antibody avelumab for patients with advanced MCC and
      the limited and controversial data on chemotherapy, it is important to put in
      perspective whether conventional chemotherapy should remain an option for these
      patients. Here, we review the evidence and controversies around chemotherapy in
      MCC as well as two recent studies on immunotherapy that changed the treatment
      paradigm for this disease.

PMID- 29033593
TI  - Expression profiling of adhesion proteins during prenatal and postnatal liver
      development in rats.
AB  - Culturing of primary hepatocytes and stem cell-derived hepatocytes faces a major
      issue of dedifferentiation due to absence of cell-cell adhesion and 3D
      structures. One of the possible ways to eliminate the problem of
      dedifferentiation is mimicking the expression pattern of adhesion proteins during
      the normal developmental process of liver cells. The purpose of this study was to
      evaluate the expression pattern of some key adhesion proteins, namely, E
      cadherin, N-cadherin, epithelial CAM (EpCAM), intracellular CAM (ICAM), collagen
      1alpha1, alpha-actinin, beta-catenin and vimentin, in the liver tissue during
      prenatal and postnatal stages. Furthermore, differences in their expression
      between prenatal, early postnatal and adult stages were highlighted. Wistar rats
      were used to isolate livers at prenatal Day 14 and 17 as well as on postnatal Day
      1, 3, 7 and 14. The liver from adult rats was used as control. Both conventional
      and real-time quantitative polymerase chain reactions (PCRs) were performed. For
      most of the adhesion proteins such as E-cadherin, N-cadherin, EpCAM, ICAM,
      collagen 1alpha1 and alpha-actinin, low expression was observed around prenatal
      Day 14 and an increasing expression was observed in the postnatal period.
      Moreover, beta-catenin and vimentin showed higher expression in the early
      prenatal period, which decreased gradually in the postnatal period, but still
      this low expression was considerably higher than that in the adult control rats.
      This basic knowledge of the regulation of expression of adhesion proteins during
      different developmental stages indicates their vital role in liver development.
      This pattern can be further studied and imitated under in vitro conditions to
      achieve better cell-cell interactions.

PMID- 29033594
TI  - Cost-effectiveness analysis of intravenous ferumoxytol for the treatment of iron
      deficiency anemia in adult patients with non-dialysis-dependent chronic kidney
      disease in the USA.
AB  - OBJECTIVE: Ferumoxytol has demonstrated superior efficacy compared with oral iron
      in treating iron deficiency anemia in chronic kidney disease (CKD) patients.
      However, an economic evaluation of ferumoxytol has not been conducted. The aim of
      this study was to analyze the cost-effectiveness of treating iron deficiency
      anemia in adult non-dialysis-dependent CKD patients with ferumoxytol as compared
      with oral iron, alone or in combination with erythropoietin-stimulating agents
      (ESAs). METHODS: A decision analytic model compared health outcomes and costs
      associated with 5-week outpatient treatment of adult non-dialysis-dependent CKD
      patients with ferumoxytol or oral iron, each as monotherapy or in combination
      with ESAs in the USA. Direct costs include the following: drug acquisition and
      administration, adverse events, and medical management. Efficacy was determined
      as mean increase in hemoglobin (g/dL) from baseline over the 5-week period.
      Clinical inputs were derived from patient-level data from two Phase III
      randomized controlled trials of ferumoxytol vs. oral iron in non-dialysis
      dependent CKD patients, and cost inputs from RED BOOKTM and Centers for Medicare
      and Medicaid Services data. Sensitivity analyses were performed to identify cost
      drivers and assess the stability of results. RESULTS: The 5-week treatment cost
      was $2,489, $5,216, $1,298, and $4,263 per patient for ferumoxytol, ferumoxytol
      with ESAs, oral iron, and oral iron with ESAs, respectively. The corresponding
      incremental costs per g/dL increase in hemoglobin, relative to ferumoxytol alone,
      were $398, $3,558, and $4,768 per patient. Efficacy was the main driver of cost
      effectiveness for all treatments. Adverse event and medical management costs were
      the principal drivers of oral iron monotherapy costs, while drug acquisition
      substantially contributed to the overall cost for the remaining treatments.
      CONCLUSION: These results suggest that ferumoxytol is a cost-effective treatment
      for iron deficiency anemia in non-dialysis-dependent CKD patients over a 5-week
      period compared with oral iron with or without ESAs. Ferumoxytol is more cost
      effective as monotherapy.

PMID- 29033595
TI  - Drug tendering: drug supply and shortage implications for the uptake of
      biosimilars.
AB  - Due to the continued increase in global spending on health care, payers have
      introduced a number of programs, policies, and agreements on pharmaceutical
      pricing in order to control costs. While incentives to increase generic drug use
      have achieved significant savings, other cost-containment measures are required.
      Tendering is a formal procedure to purchase medications using competitive bidding
      for a particular contract. Although useful for cost containment, tendering can
      lead to decreased competition in a given market. Consequently, drug shortages can
      occur, resulting in changes to treatment plans to products that may have lower
      efficacy and/or an increased risk of adverse effects. Therefore, care must be
      taken to ensure that tendering does not negatively impact patient care or the
      health care system. A large and expanding portion of total pharmaceutical
      expenditure is for biologic therapies. These agents have revolutionized the
      treatment of many diseases, including cancer and inflammatory conditions;
      however, patient access to biologic drugs can be limited due to availability,
      insurance coverage, and cost. As branded biologic therapies reach the end of
      patent- and data-protection periods, biosimilars are being approved as lower-cost
      alternatives. Biosimilars are products that are highly similar to the originator
      product with no clinically meaningful differences in terms of safety, purity, or
      potency. As more biosimilars receive regulatory approval and adoption increases,
      these therapies are expected to have an impact on global health care spending and
      should result in overall savings. However, the use of tendering to maximize the
      potential benefits of biosimilars has varied across the world. Therefore, the
      objectives of this review are to examine the drug-tendering process and its
      implications on drug supply and drug shortages, as well as to describe
      biosimilars and how tendering may influence their uptake.

PMID- 29033596
TI  - Metabolic syndrome remission after Roux-en-Y gastric bypass or sleeve
      gastrectomy.
AB  - BACKGROUND: Bariatric surgery is known to decrease weight and the prevalence of
      comorbidities, but there is little evidence on the differential effect of Roux-en
      Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on the remission of the
      aggregate outcome, metabolic syndrome, 4 years after surgery. The purpose of this
      study was to determine the effectiveness of RYGB and SG on metabolic syndrome in
      veterans. METHODS: We retrospectively reviewed consecutive patients who underwent
      SG and RYGB at the Dallas Veterans Affairs Medical Center from 2003 to 2012. We
      determined the effect of both the operations on the remission of metabolic
      syndrome, its individual components, and medium-term morbidity and mortality. A
      sensitivity analysis was performed using propensity matching. RESULTS: A total of
      266 patients were identified (159 RYGB and 107 SG) with 96% follow-up after 4
      years. The mean age of the cohort was 51.4 years; the majority of patients were
      male (59%) and Caucasian (69%). RYGB patients had a greater mean body mass index
      and were more likely to have hypertension or hypertriglyceridemia. RYGB was
      associated with a similar metabolic syndrome remission to SG (37.6% vs 26.8%;
      P=0.09). The percentage of weight loss was 26.5% after RYGB and 10.8% after SG at
      4 years post operation (P<0.01). Predictors of metabolic syndrome persistence
      were male gender, type 2 diabetes, and low high-density lipoprotein. While both
      the operations were associated with similar mortality (RYGB 4.4%, SG 2.8%;
      P=0.74), RYGB was associated with a greater rate of morbidity. CONCLUSION: RYGB
      and SG seem to be associated with similar remission rates of metabolic syndrome
      at 4 years. RYGB yields greater weight loss with greater medium-term
      complications.

PMID- 29033597
TI  - Reasons for discontinuation of GLP1 receptor agonists: data from a real-world
      cross-sectional survey of physicians and their patients with type 2 diabetes.
AB  - AIM: Nonadherence to glucagon-like peptide-1 receptor agonists (GLP1 RAs) is
      relatively common among patients with type 2 diabetes mellitus (T2DM). This study
      sought to identify reasons why patients discontinue GLP1 RAs. MATERIALS AND
      METHODS: Retrospective data from the Adelphi Diabetes Disease Specific Programme
      were used. Physicians managing patients with T2DM were surveyed via face-to-face
      interviews, and patients treated for T2DM were surveyed via self-completed
      questionnaires. Patient data were stratified by current versus prior GLP1 RA use.
      RESULTS: Physicians (n=443) most frequently reported inadequate blood glucose
      control (45.6%), nausea/vomiting (43.8%), and gastrointestinal (GI) side effects
      (36.8%) as reasons for GLP1 RA discontinuation. Patients (n=194) reported the GI
      related issues "Made me feel sick" (64.4%) and "Made me throw up" (45.4%) as
      their top reasons for discontinuation. The most common problems reported
      (excluding cost) for those currently using GLP1 RAs were "Prefer oral medication
      over injections" (patients 56%, physicians 32.6%), "Made me feel sick" (patients
      38.1%, physicians 16.3%), and "Did not help lose weight" (patients 25.4%,
      physicians 18%). The most bothersome problems for patients globally (frequency
      reporting very/extremely bothersome) (excluding cost) were "Difficult to plan
      meals around" (55.6%), "Made me throw up" (51.6%), and "Caused weight gain"
      (50%). CONCLUSION: Both patients and physicians reported GI-related issues as a
      prominent factor, but disparities between patient experiences and physician
      perceptions were revealed, suggesting gaps in physician-patient communication.
      Understanding patients' expectations of GLP1 RAs and physicians' patient
      management practices may help increase GLP1 RA adherence and thereby potentially
      enhance diabetes care.

PMID- 29033598
TI  - Calcipotriene/betamethasone dipropionate for the treatment of psoriasis vulgaris:
      an evidence-based review.
AB  - While topical medications remain the cornerstone of the psoriasis treatment
      paradigm, they also come with the risk of multiple side effects. An alternative
      topical treatment option, calcipotriene or calcipotriol, is a vitamin D
      derivative that is thought to work by inhibiting keratinocyte proliferation and
      enhancing keratinocyte differentiation. Multiple studies have demonstrated its
      efficacy and safety in improving psoriasis when used in combination with topical
      corticosteroids. Given the effectiveness and side effect profile seen with this
      combination of topical steroid and calcipotriene, the US Food and Drug
      Administration approved a calcipotriene/betamethasone dipropionate product for
      use in psoriasis patients over the age of 12 in 2006. Our paper seeks to review
      clinical trial evidence of this combination medication and its use in the
      treatment of psoriasis vulgaris. While assessment of available evidence indicates
      that the topical medication is both safe and effective for the treatment of
      psoriasis vulgaris, addressing limitations of what is known, such as
      tolerability, adherence, and patient preference, of this combination drug in
      future high-impact studies is needed.

PMID- 29033600
TI  - Efficacy and safety of subcutaneous administration of lyophilized powder of alfa
      erythropoietin to maintain hemoglobin concentrations among hemodialysis patients.
AB  - BACKGROUND: Anemia associated with chronic kidney disease (CKD) often requires
      treatment with recombinant human erythropoietin (EPO). This study investigated
      the therapeutic equivalence between lyophilized powder and standard liquid EPO
      alfa by subcutaneous (SC) administration in hemoglobin maintenance among patients
      on hemodialysis. METHODS: This was a single-blinded, randomized, controlled,
      single-center, parallel-group study regarding the treatment of anemia among CKD
      patients on hemodialysis and being treated with stable doses of EPO alfa at least
      for 12 weeks. Anemic hemodialysis patients (n=63) received standard liquid or
      lyophilized powder EPO alfa for 24 weeks by SC administration. Achievement of the
      target hemoglobin concentration and safety and tolerability end points were
      documented. RESULTS: Baseline mean hemoglobin level was 11.1+/-0.7 g/dL using
      lyophilized powder EPO alfa and 11.2+/-0.9 g/dL using standard liquid EPO alfa.
      The baseline median dose of EPO alfa was 126.4 (interquartile range [IQR] 81.6
      163.6) U/kg/week in the lyophilized powder EPO alfa group and 116.9 (IQR 76.5
      144.1) U/kg/week in the standard liquid EPO alfa group. Treatment with SC
      lyophilized powder EPO alfa maintained mean hemoglobin and hematocrit
      concentrations after switching from standard liquid EPO alfa. No statistical
      significance between groups was reported for hemoglobin concentrations and weekly
      dose of EPO alfa during the study. No safety concerns were raised, including
      positive anti-EPO antibodies. CONCLUSION: In this study of anemia therapy among
      patients with end-stage renal disease on hemodialysis therapy, the SC injection
      of lyophilized powder EPO alfa was well tolerated and effectively maintained
      hemoglobin levels. Future studies of larger size and longer duration will be
      required to assess safety profiles.

PMID- 29033599
TI  - Primary ciliary dyskinesia: mechanisms and management.
AB  - Primary ciliary dyskinesia is a genetically heterogeneous disorder of motile
      cilia that is predominantly inherited in an autosomal-recessive fashion. It is
      associated with abnormal ciliary structure and/or function leading to chronic
      upper and lower respiratory tract infections, male infertility, and situs
      inversus. The estimated prevalence of primary ciliary dyskinesia is approximately
      one in 10,000-40,000 live births. Diagnosis depends on clinical presentation,
      nasal nitric oxide, high-speed video-microscopy analysis, transmission electron
      microscopy, genetic testing, and immunofluorescence. Here, we review its clinical
      features, diagnostic methods, molecular basis, and available therapies.

PMID- 29033601
TI  - Urine metabolic ratio of omeprazole in relation to CYP2C19 polymorphisms in
      Russian peptic ulcer patients.
AB  - BACKGROUND: CYP2C19 is known to be the main enzyme of biotransformation of proton
      pump inhibitors (PPIs), whereas the CYP2C19 gene is highly polymorphic.
      Genotyping and phenotyping together represent more reliable data about patient's
      CYP2C19 activity. PURPOSE: The aim of the study was to investigate the
      applicability of urine metabolic ratio of omeprazole for CYP2C19 phenotyping in
      Russian peptic ulcer patients with different CYP2C19 genotypes. PATIENTS AND
      METHODS: A total of 59 patients (19 men and 40 women) aged 18-91 years (mean age
      53.5+/-15.1 years) from four Moscow clinics who were diagnosed with an
      endoscopically and histologically proven peptic ulcer or had a history of
      endoscopically and histologically proven ulcers in the past were recruited.
      Peripheral venous blood (6 mL) was collected for DNA extraction, and real-time
      polymerase chain reaction was performed for the analysis of CYP2C19*2G681A
      (rs4244285), CYP2C19*3G636A (rs4986893) and CYP2C19*17C-806T (rs12248560)
      polymorphisms. Urine samples of patients were collected in the morning between 6
      am and 9 am, before food or drug intake, after at least 3 days of twice daily
      (b.i.d.) omeprazole intake. Omeprazole and 5-hydroxyomeprazole concentrations in
      the urine were measured using high-performance liquid chromatography with mass
      spectrometry. RESULTS: Of the 59 patients, there were 27 (45.8%) extensive
      metabolizers (EMs; CYP2C19*1/*1), 16 (27.1%) ultrarapid metabolizers (UMs;
      CYP2C19*1/*17, CYP2C19*17/*17), 14 (23.7%) intermediate metabolizers (IMs;
      CYP2C19*1/*2, CYP2C19*2/*17, CYP2C19*3/*17) and two (3.4%) poor metabolizers
      (PMs; CYP2C19*2/*2). Median metabolic ratio (25%-75% percentiles) were 1.03 (0.69
      1.36) for EMs, 1.95 (1.33-2.68) for UMs, 1.40 (0.78-2.13) for IMs+PMs and 1.26
      (0.82-1.99) for the whole sample. A statistically significant difference in
      metabolic ratio (Mann-Whitney U test) was found between UMs and EMs (p=0.001) and
      in the multiple comparison Kruskal-Wallis test (p=0.005). CONCLUSION: We found a
      connection between particular CYP2C19 genotypes and urine metabolic ratio of
      omeprazole in Russian peptic ulcer patients. This method needs to be improved as
      in our modification it worked mainly for UMs and did not differentiate all
      patients according to omeprazole biotransformation activity.

PMID- 29033602
TI  - Early in-hospital clinical deterioration is not predicted by severity of illness,
      functional status, or comorbidity.
AB  - BACKGROUND: Prior studies concentrated on unplanned intensive care unit (ICU)
      transfer to gauge deterioration occurring shortly following hospital admission.
      However, examining only ICU transfers is not ideal since patients could stabilize
      with treatment, refuse ICU admission, or not require ICU evaluation. To further
      explore etiologies of early clinical deterioration, we used rapid response team
      (RRT) activation within 48 hours of admission as an index of early clinical
      worsening. METHODS: A retrospective analysis of prospectively gathered admissions
      from the emergency department in an academic medical center was done. Data were
      reviewed independently by two physicians. We assessed severity of illness,
      functional status, comorbidity, the frequency of ICU and palliative care
      consultations, and changes in advance health care directives. RESULTS: Of 655
      rapid responses (RRs) within the study period, 24.6% occurred within 48 hours of
      admission. Disease trajectory was the most frequent perceived reason for RRs
      (55.6% and 58.9%, reviewer 1 and 2, respectively) followed by medical error
      (15.6% and 15.2%). Acute physiology and chronic health evaluation II (APACHE-II)
      and modified early warning scores (MEWS) were higher at the time of RR compared
      to admission (p<0.0001). However, admission APACHE-II, MEWS, functional status,
      and comorbidity scores did not predict early RRs. One third of RRs resulted in
      ICU consultation and 95% were accepted. Palliative care consults were requested
      for 15%, the majority (65%) after RR and all resulting in advance directive
      change. CONCLUSION: Disease trajectory accounted for most clinical deterioration
      and medical error contributed to 15%. Our data suggest that it is difficult to
      predict early clinical deterioration as none of the measured parameters were
      associated with RRT activation.

PMID- 29033603
TI  - Application of the chronic constriction injury of the partial sciatic nerve model
      to assess acupuncture analgesia.
AB  - PURPOSE: To validate and explore the application of a rat model of chronic
      constriction injury to the partial sciatic nerve in investigation of acupuncture
      analgesia. METHODS: Chronic constriction injury of the sciatic nerve (CCI) and
      chronic constriction injury of the partial sciatic nerve (CCIp) models were
      generated by ligating either the sciatic nerve trunk or its branches in rats.
      Both models were evaluated via paw mechanical withdrawal latency (PMWL), paw
      mechanical withdrawal threshold (PMWT), nociceptive reflex-induced electromyogram
      (C-fiber reflex EMG), and dorsal root ganglion immunohistochemistry.
      Electroacupuncture (EA) was performed at GB30 to study the analgesic effects on
      neuropathic pain and the underlying mechanisms. RESULTS: Following ligation of
      the common peroneal and tibial nerves, CCIp rats exhibited hindlimb dysfunction,
      hind paw shrinkage and lameness, mirroring those of CCI rats (generated by
      ligating the sciatic nerve trunk). Compared to presurgery measurements, CCIp and
      CCI modeling significantly decreased the PMWL and PMWT. EA at GB30 increased the
      PMWL and PMWT in both CCI and CCIp rats. Calcitonin gene-related polypeptide and
      substance P expressions were apparently increased in both CCI and CCIp groups,
      but were not different from each other. The C-fiber reflex EMG of the biceps
      femoris was preserved in CCIp rats, but it could not be recorded in CCI rats on
      the 5th day after nerve ligation. The C-fiber reflex EMG was reduced at 0, 1, and
      2 minutes after EA in CCIp rats, but only at 0 and 1 minute after EA in normal
      rats. CONCLUSION: The CCIp model is better than the CCI model for studying
      acupuncture analgesia on chronic neuropathic pain and the underlying mechanisms.

PMID- 29033604
TI  - Chronic pain and adult hippocampal neurogenesis: translational implications from
      preclinical studies.
AB  - Adult hippocampal neurogenesis (ahNG) occurs in the human brain. Adult generated
      neurons have been proposed to functionally contribute to relevant hippocampal
      functions such as learning and memory, mood regulation, and stress response.
      Learning, environmental enrichment, and physical exercise exert positive effects
      on ahNG. In parallel, these proneurogenic stimuli have been shown to ameliorate
      cognitive performance and/or depressive-like behavior in animal models.
      Conversely, aging, social isolation, and chronic stress exert negative effects on
      ahNG. Interestingly, reduction of hippocampal neurogenesis is suggested to
      potentially contribute to cognitive decline and mood alterations associated with
      aging and several neuropsychiatric disorders. Clinical observation demonstrates
      that patients affected by chronic pain often exhibit increased anxiety and
      depression, impaired cognitive flexibility, and memory capacities. As of today,
      our understanding of the molecular and cellular events that may underlie the
      comorbidity of chronic pain, depression, and cognitive impairment is limited.
      Herein we review recent preclinical data suggesting that chronic pain may induce
      profound changes in hippocampal plasticity, including reduced ahNG. We discuss
      the possibility that deregulated hippocampal neurogenesis in chronic pain may, at
      least in part, contribute to cognitive and mood alterations. Based on this
      hypothesis, the mechanisms underlying chronic pain-associated changes in
      hippocampal neurogenesis and related functions need to be addressed
      experimentally. One interesting feature of ahNG is its susceptibility to
      pharmacological modulation. Again, based on preclinical data we discuss the
      possibility that, at least in principle, distinct analgesic drugs commonly used
      in chronic pain states (typical and atypical opiates, alpha2delta ligands, and
      acetyl-l-carnitine) may differentially impact ahNG and that this aspect could be
      taken into account to reduce and/or prevent the potential risk of cognitive and
      emotional side effects in the clinical setting.

PMID- 29033605
TI  - Onabotulinum toxin A in the treatment of chronic migraine: patient selection and
      special considerations.
AB  - Discovered by serendipity, onabotulinum toxin A (BoNT-A) is the only US Food and
      Drug Administration-approved treatment for the prevention of chronic migraine
      (CM), one of the most disabling and burdensome human conditions. Its efficacy,
      safety and tolerability, proved by the largest and longest migraine therapeutic
      trial (the Phase III Research Evaluating Migraine Prophylaxis Therapy program
      [PREEMPT]), have been replicated by various real-life studies also in the
      presence of medication overuse. The benefit of BoNT-A prophylaxis is likely due
      to its ability to counteract peripheral and central nociceptive sensitization
      through reversible chemical denervation of pericranial sensitive afferents. Its
      efficacy increases considerably over time during long-term treatments,
      significantly varying among patients. The present review focuses on the state-of
      the art of current knowledge on putative instrumental, biochemical and clinical
      predictors of BoNT-A responsiveness, outlining the need for a thorough
      characterization of the full phenotypic migraine picture when trying to predict
      good responders. Available evidence suggests that disentangling the BoNT-A
      responsiveness puzzle requires 1) a reappraisal of easy-obtainable clinical
      details (eg, site and quality of pain, presence of cranial autonomic symptoms),
      2) a proper stratification of patients with CM according to their headache
      frequency, 3) the evaluation of potential synergistic effects of concomitant
      prophylaxis/treatment and 4) a detailed assessment of modifiable risk factors
      evolution during treatment.

PMID- 29033606
TI  - The pain, depression, disability pathway in those with low back pain: a
      moderation analysis of health locus of control.
AB  - Low back pain (LBP) is common, impacts on the individual and society, and is a
      major health concern. Psychological consequences of LBP, such as depression, are
      significant barriers to recovery, but mechanisms for the development of
      depression are less well understood. One potential mechanism is the individual's
      health locus of control (HLoC), that is, perception of the level of control an
      individual has over their health. The objective of this study is to investigate
      the moderation effect of HLoC on the pain-depression-disability pathway in those
      with LBP. The design is a nested cross-sectional analysis of two existing cohorts
      of patients (n=637) who had previously consulted their primary care physician
      about LBP. Measures were taken of HLoC, pain intensity and interference,
      depression, disability, and bothersomeness. Structural Equation Modeling analysis
      was applied to two path models that examined the pain to depression to disability
      pathway moderated by the HLoC constructs of Internality and Externality,
      respectively. Critical ratio (CR) difference tests were applied to the
      coefficients using pairwise comparisons. The results show that both models had an
      acceptable model fit and pathways were significant. CR tests indicated a
      significant moderation effect, with stronger pathway coefficients for depression
      for those who report low Internality (beta 0.48), compared to those with high
      Internality (beta 0.28). No moderation effects were found within the Externality
      model. HLoC Internality significantly moderates the pain-depression pathway in
      those with LBP, meaning that those who have a low perception of control report
      greater levels of depression. HLoC may signify depression among people with LBP,
      and could potentially be a target for intervention.

PMID- 29033607
TI  - Profiling of gene expression regulated by 17beta-estradiol and tamoxifen in
      estrogen receptor-positive and estrogen receptor-negative human breast cancer
      cell lines.
AB  - One area of great importance in breast cancer (BC) research is the study of gene
      expression regulated by both estrogenic and antiestrogenic agents. Although many
      studies have been performed in this area, most of them have only addressed the
      effects of 17beta-estradiol (E2) and tamoxifen (TAM) on MCF7 cells. This study
      aimed to determine the effect of low doses of E2 and TAM on the expression levels
      of 84 key genes, which are commonly involved in breast carcinogenesis, in four BC
      cell lines differentially expressing estrogen receptor (ER) alpha and HER2 (MCF7,
      T47D, BT474, and SKBR3). The results allowed us to determine the expression
      patterns modulated by E2 and TAM in ERalpha+ and ERalpha- cell lines, as well as
      to identify differences in expression patterns. Although the MCF7 cell line is
      the most frequently used model to determine gene expression profiles in response
      to E2 and TAM, the changes in gene expression patterns identified in ERalpha+ and
      ERalpha- cell lines could reflect distinctive properties of these cells. Our
      results could provide important markers to be validated in BC patient samples,
      and subsequently used for predicting the outcome in ERalpha+ and ERalpha- tumors
      after TAM or hormonal therapy. Considering that BC is a molecularly heterogeneous
      disease, it is important to understand how well, and which cell lines, best model
      that diversity.

PMID- 29033609
TI  - Clinical implications of six inflammatory biomarkers as prognostic indicators in
      Ewing sarcoma.
AB  - Cancer-related systemic inflammation responses have been correlated with cancer
      development and progression. The prognostic significance of several inflammatory
      indicators, including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte
      ratio (PLR), Glasgow Prognostic Score (GPS), C-reactive protein to albumin ratio
      (CRP/Alb ratio), lymphocyte-monocyte ratio (LMR), and neutrophil-platelet score
      (NPS), were found to be correlated with prognosis in several cancers. However,
      the prognostic role of these inflammatory biomarkers in Ewing sarcoma has not
      been evaluated. This study enrolled 122 Ewing patients. Receiver operating
      characteristic (ROC) analysis was generated to determine optimal cutoff values;
      areas under the curves (AUCs) were assessed to show the discriminatory ability of
      the biomarkers; Kaplan-Meier analysis was conducted to plot the survival curves;
      and Cox multivariate survival analysis was performed to identify independent
      prognostic factors. The optimal cutoff values of CRP/Alb ratio, NLR, PLR, and LMR
      were 0.225, 2.38, 131, and 4.41, respectively. CRP/Alb ratio had a significantly
      larger AUC than NLR, PLR, LMR, and NPS. Higher levels of CRP/Alb ratio (hazard
      ratio [HR] 2.41, P=0.005), GPS (HR 2.27, P=0.006), NLR (HR 2.07, P=0.013), and
      PLR (HR 1.85, P=0.032) were significantly correlated with poor prognosis. As the
      biomarkers had internal correlations, only the CRP/Alb ratio was involved in the
      multivariate Cox analysis and remained an independent prognostic indicator. The
      study demonstrated that CRP/Alb ratio, GPS, and NLR were effective prognostic
      indicators for patients with Ewing sarcoma, and the CRP/Alb ratio was the most
      robust prognostic indicator with a discriminatory ability superior to that of the
      other indicators; however, PLR, LMR, and NPS may not be suitable as prognostic
      indicators in Ewing sarcoma.

PMID- 29033610
TI  - A pilot randomized controlled clinical trial of second uterine curettage versus
      usual care to determine the effect of re-curettage on patients' need for
      chemotherapy among women with low risk, nonmetastatic gestational trophoblastic
      neoplasm in Urmia, Iran.
AB  - OBJECTIVE: The objective of this study was to determine if second curettage was
      associated with a decreased need for the number of chemotherapy treatments
      compared to usual care. METHODS: A pilot randomized controlled clinical trial was
      designed at Motahhari Referral Hospital in 2014. Fifty-two patients with low
      risk, nonmetastatic gestational trophoblastic neoplasm were assigned randomly to
      two arms. The interventional arm included a repeat uterine curettage, and the
      control group received standard care (chemotherapy). All participants were
      followed periodically over 6 months. Primary outcome was defined as the number of
      chemotherapy courses in each arm. Student's t-test and receiver operator
      characteristics (ROC) curve were applied for statistical analysis as appropriate.
      RESULTS: Fifty percent of participants who underwent re-curettage did respond to
      intervention with no further chemotherapy after 6 months of follow-up. The
      intervention arm had higher number of remissions without chemotherapy compared to
      those who received usual care. In the subgroup analysis, the ROC curve could
      predict the re-curettage treatment response by beta human chorionic gonadotropin
      (BhCG) level significantly. No complications were reported in the intervention
      arm. CONCLUSION: Second curettage is an alternative effective procedure to
      decrease the need for chemotherapy among patients with low risk, nonmetastatic
      gestational trophoblastic neoplasm. Further clinical trials with larger sample
      size may be needed to determine the effective role of second curettage among
      patients.

PMID- 29033608
TI  - Is the prognostic significance of O6-methylguanine- DNA methyltransferase
      promoter methylation equally important in glioblastomas of patients from
      different continents? A systematic review with meta-analysis.
AB  - BACKGROUND: O6-methylguanine-DNA methyltransferase (MGMT) is an independent
      predictor of therapeutic response and potential prognosis in patients with
      glioblastoma multiforme (GBM). However, its significance of clinical prognosis in
      different continents still needs to be explored. PATIENTS AND METHODS: To explore
      the effects of MGMT promoter methylation on both progression-free survival (PFS)
      and overall survival (OS) among GBM patients from different continents, a
      systematic review of published studies was conducted. RESULTS: A total of 5103
      patients from 53 studies were involved in the systematic review and the total
      percentage of MGMT promoter methylation was 45.53%. Of these studies, 16 studies
      performed univariate analyses and 17 performed multivariate analyses of MGMT
      promoter methylation on PFS. The pooled hazard ratio (HR) estimated for PFS was
      0.55 (95% CI 0.50, 0.60) by univariate analysis and 0.43 (95% CI 0.38, 0.48) by
      multivariate analysis. The effect of MGMT promoter methylation on OS was explored
      in 30 studies by univariate analysis and in 30 studies by multivariate analysis.
      The combined HR was 0.48 (95% CI 0.44, 0.52) and 0.42 (95% CI 0.38, 0.45),
      respectively. CONCLUSION: In each subgroup divided by areas, the prognostic
      significance still remained highly significant. The proportion of methylation in
      each group was in inverse proportion to the corresponding HR in the univariate
      and multivariate analyses of PFS. However, from the perspective of OS, compared
      with data from Europe and the US, higher methylation rates in Asia did not bring
      better returns.

PMID- 29033611
TI  - Stable ischemic heart disease in women: current perspectives.
AB  - Cardiovascular disease is the leading cause of death in women accounting for 1 in
      every 4 female deaths. Pathophysiology of ischemic heart disease in women
      includes epicardial coronary artery, endothelial dysfunction, coronary vasospasm,
      plaque erosion and spontaneous coronary artery dissection. Angina is the most
      common presentation of stable ischemic heart disease (SIHD) in women. Risk
      factors for SIHD include traditional risks such as older age, obesity (body mass
      index [BMI] >25 kg/m2), smoking, hypertension, dyslipidemia, cerebrovascular and
      peripheral vascular disease, sedentary lifestyle, family history of premature
      coronary artery disease, metabolic syndrome and diabetes mellitus, and
      nontraditional risk factors, such as gestational diabetes, insulin
      resistance/polycystic ovarian disease, pregnancy-induced hypertension, pre
      eclampsia, eclampsia, menopause, mental stress and autoimmune diseases.
      Diagnostic testing can be used effectively to risk stratify women. Guidelines
      directed medical therapy including aspirin, statins, beta-blocker therapy,
      calcium channel blockers and ranolazine should be instituted for symptom and
      ischemia management. Despite robust evidence regarding the adverse outcomes seen
      in women with ischemic heart disease, knowledge gaps exist in several areas.
      Future research needs to be directed toward a greater understanding of the role
      of nontraditional risk factors for SIHD in women, gaining deeper insights into
      the sex differences in therapeutic effects and formulating a sex-specific
      algorithm for the management of SIHD in women.

PMID- 29033612
TI  - Increased detection of precancerous cervical lesions with adjunctive dynamic
      spectral imaging.
AB  - OBJECTIVE: To validate, in US community-based colposcopy clinics, previous
      reports of increased detection of high-grade cervical intraepithelial neoplasia
      (CIN2+) with biopsies selected using dynamic spectral imaging (DSI) mapping after
      standard colposcopy. STUDY DESIGN: Cross-sectional observational study of 26
      colposcopists across nine clinics recruiting consecutive colposcopy patients.
      Standard assessment with biopsy selections was completed before seeing the DSI
      map which was subsequently interpreted and used for additional biopsies per
      clinical judgment. Primary measure was the number of women with CIN2+ detected by
      DSI-assisted biopsies, over those detected by standard colposcopy biopsies.
      RESULTS: A total of 887 women were recruited. After exclusions, 881 women and
      1,189 biopsies were analyzed. Standard biopsy detected 78 women with CIN2+ and
      DSI-assisted biopsies another 34, increasing the detection rate from 8.85% to
      12.71% (p=0.00016). This was achieved with 16.16% of DSI-assisted biopsies
      finding CIN2+ compared to 13.24% for the preceding standard biopsies. For
      secondary specificity analysis, 431 women had only <CIN2 in standard biopsy/ies,
      a 48.92% rate, while 131 women who underwent no standard biopsy/ies had DSI
      assisted biopsy/ies which were all <CIN2, a 35.22% rate (p<0.0001). CONCLUSION:
      The largest study, to date, of DSI used in colposcopy confirms previously
      reported increased detection of CIN2+, across multiple US community-based
      clinics. Based on the improved efficiency of the DSI-assisted biopsies, this
      increase suggests an improved diagnostic capacity achieved with DSI and cannot be
      explained solely by the taking of additional biopsies.

PMID- 29033613
TI  - Let us fight and support one another: adolescent girls and young women on
      contributors and solutions to HIV risk in Zambia.
AB  - In Zambia, adolescent girls and young women (AGYW) are disproportionately
      affected by human immunodeficiency virus (HIV), social, cultural and economic
      factors making them particularly vulnerable. This study was designed to
      understand the context in which AGYW are at risk and to identify perceived
      drivers of the epidemic and potential strategies to reduce HIV risk. Focus group
      discussions were conducted with AGYW in Zambian districts with the highest HIV
      prevalence from February through August 2016. The focus group guide addressed HIV
      risk factors and strategies for HIV prevention in AGYW. Focus group discussions
      were recorded, translated and transcribed, themes identified and responses coded.
      Results suggest that gender inequality undermined potentially protective factors
      against HIV among AGYW. Poverty and stigmatization were major barriers to
      accessing available HIV prevention services as well as primary risk factors for
      HIV infection. Sponsorship to support AGYW school attendance, programs for boys
      and girls to foster gender equality and financial assistance from the government
      of Zambia to support AGYW most in need were proposed as strategies to reduce HIV
      risk. Results highlight the utility of using community-based research to guide
      potential interventions for the affected population. Future research should
      explore the use of multilevel interventions to combat HIV among AGYW.

PMID- 29033614
TI  - Fusion of lower limbs with severe urogenital malformation in a newborn, a rare
      congenital clinical syndrome: case report.
AB  - BACKGROUND: Fused lower limbs combined with severe urogenital malformation, also
      known as sirenomelia, is a rare congenital clinical syndrome. The etiology is
      unknown, and the outcome for the affected fetus is rather uncertain. CASE REPORT:
      Mrs RB, a Kuwaiti woman primigravida, married to a non-consanguineous husband,
      had uneventful antenatal care in a private health service, until she was admitted
      to the Maternity Hospital, Kuwait, at 31 weeks of gestation with a 3-hour history
      of ruptured membranes. She had a negative family history for diabetes mellitus,
      and her past surgical/medical/gynecological history was noncontributory. General
      physical examination revealed a healthy parturient with normal vital signs, clear
      lungs and normal heart sounds. Obstetric examination revealed a fundal height
      compatible with the gestational age; there was a single living fetus in breech
      presentation; she was not in labor. The mother was managed conservatively with
      antibiotics and dexamethasone injections. Labor ensued later, progressing rapidly
      to the second stage. Assisted breech delivery was performed, and a live baby,
      birth weight 1570 g and Apgar score 3/9, was delivered. The neonate had multiple
      congenital abnormalities, including fusion of both lower limbs, ambiguous
      genitalia, cloacal anomaly and tracheoesophageal fistula. The neonate was
      admitted to the neonatal intensive care unit, fully investigated, managed
      medically and surgically and eventually discharged home after a hospital stay of
      123 days for further management. CONCLUSION: A case of peculiar fetal anomaly
      called sirenomelia, the first case in Kuwait, has been presented. Survival of
      such babies requires costly management with average results.

PMID- 29033615
TI  - Clinical, economic, and humanistic burden of needlestick injuries in healthcare
      workers.
AB  - INTRODUCTION: Needlestick injuries (NSIs) from a contaminated needle put
      healthcare workers (HCWs) at risk of becoming infected with a blood-borne virus
      and suffering serious short- and long-term medical consequences. Hypodermic
      injections using disposable syringes and needles are the most frequent cause of
      NSIs. OBJECTIVE: To perform a systematic literature review on NSI and active
      safety-engineered devices for hypodermic injection. METHODS: MEDLINE, EMBASE, and
      COCHRANE databases were searched for studies that evaluated the clinical,
      economic, or humanistic outcomes of NSI or active safety-engineered devices.
      RESULTS: NSIs have been reported by 14.9%-69.4% of HCWs with the wide range due
      to differences in countries, settings, and methodologies used to determine rates.
      Exposure to contaminated sharps is responsible for 37%-39% of the worldwide cases
      of hepatitis B and C infections in HCWs. HCWs may experience serious emotional
      effects and mental health disorders after a NSI, resulting in work loss and post
      traumatic stress disorder. In 2015 International US$ (IntUS$), the average cost
      of a NSI was IntUS$747 (range IntUS$199-1,691). Hypodermic injections, the most
      frequent cause of NSI, are responsible for 32%-36% of NSIs. The use of safety
      devices that cover the needle-tip after hypodermic injection lowers the risk of
      NSI per HCW by 43.4%-100% compared to conventional devices. The economic value of
      converting to safety injective devices shows net savings, favorable budget
      impact, and overall cost-effectiveness. CONCLUSION: The clinical, economic, and
      humanistic burden is substantial for HCWs who experience a NSI. Safety-engineered
      devices for hypodermic injection demonstrate value by reducing NSI risk, and the
      associated direct and indirect costs, psychological stress on HCWs, and
      occupational blood-borne viral infection risk.

PMID- 29033616
TI  - Nationwide trends of clinical characteristics and economic burden of emergency
      department visits due to acute ischemic stroke.
AB  - We aimed to provide estimates of the volume and associated charges of acute
      ischemic stroke (AIS) visits in the US, as well as to assess predictors of
      patient disposition following an emergency department (ED) visit for AIS. Our
      study was conducted using the 2010-2013 data from the Nationwide Emergency
      Department Sample. We identified adult visits with AIS as the primary diagnosis.
      A generalized linear model was used to calculate mean charges per visit after
      adjusting for covariates. Multinomial logistic regression was used to assess
      predictors of patient disposition following an ED visit for AIS. The national
      incidence did not appreciably change over time, increasing from 26.4 to 27.0
      visits per 10,000 adults. Adjusted mean charges per event were highest in the
      West, increasing from $3,761 in 2010 to $4,575 in 2013. Multinomial logistic
      regression showed that older age was associated with increased likelihood of both
      hospital admission and mortality in the ED, while male sex was associated with
      lower odds of mortality in the ED. Despite improvements in primary and secondary
      prevention of cardiovascular disease, AIS remains a significant burden on the
      health care system with a high volume of ED visits and increasing charges for
      care.

PMID- 29033617
TI  - Family accommodation in adult obsessive-compulsive disorder: clinical
      perspectives.
AB  - The term accommodation has been used to refer to family responses specifically
      related to obsessive-compulsive (OC) symptoms: it encompasses behaviors such as
      directly participating in compulsions, assisting a relative with obsessive
      compulsive disorder (OCD) when he/she is performing a ritual, or helping him/her
      to avoid triggers that may precipitate obsessions and compulsions. At the
      opposite side, family responses to OCD may also include interfering with the
      rituals or actively opposing them; stopping accommodating OC symptoms or actively
      interfering with their performance is usually associated with greater distress
      and sometimes even with aggressive behaviors from the patients. This article
      summarizes progress of the recent research concerning family accommodation in
      relatives of patients with OCD. Family accommodation is a prevalent phenomenon
      both among parents of children/adolescents with OCD and relatives/caregivers of
      adult patients. It can be measured with a specific instrument, the Family
      Accommodation Scale, of which there are several versions available for use in
      clinical practice. The vast majority of both parents of children/adolescents with
      OCD and family members of adult patients show at least some accommodation;
      providing reassurances to obsessive doubts, participating in rituals and
      assisting the patient in avoidance are the most frequent accommodating behaviors
      displayed by family members. Modification of routine and modification of
      activities specifically due to OC symptoms have been found to be equally
      prevalent. Specific characteristics of patients (such as contamination/washing
      symptoms) and of relatives (the presence of anxiety or depressive symptoms or a
      family history positive for another anxiety disorder) are associated with a
      higher degree of family accommodation; these family members may particularly
      benefit from family-based cognitive-behavioral interventions. In recent years,
      targeting family accommodation has been suggested as a fundamental component of
      treatment programs and several interventions have been tested. Clinicians should
      be aware that family-based cognitive-behavior therapy incorporating modules to
      target family accommodation is more effective in reducing OC symptoms. Targeting
      family accommodation may be as well relevant for patients treated
      pharmacologically.

PMID- 29033619
TI  - Observation and Interview-based Diurnal Sleepiness Inventory for measurement of
      sleepiness in older adults.
AB  - INTRODUCTION: There is no established reference standard for subjective measures
      of sleepiness in older adults. METHODS: This study compares the Observation and
      Interview-based Diurnal Sleepiness Inventory (ODSI) with two existing instruments
      for measurement of sleepiness and daily functioning, the Epworth Sleepiness Scale
      (ESS) and Functional Outcomes of Sleep Questionnaire (FOSQ). RESULTS: A total of
      125 study participants were included in this study and were administered the
      ODSI, ESS and FOSQ; subjects had a mean age of 70.9 +/- 5.27 years, mean Apnea
      Hypopnea Index of 31.9 +/- 27.9 events/hour and normal cognitive functioning
      (Mini-Mental State Examination score > 24). The ODSI showed a significant
      association with the ESS (Spearman's rho: 0.67, P < 0.001) and with the FOSQ
      (Spearman's rho: -0.52, P < 0.001). The ODSI 1 item (assessing sleepiness in
      active situations) was borderline significantly correlated with the ESS (beta =
      0.14; 95% confidence interval [CI], -0.01 to 0.29; P = 0.069). ODSI 2 item
      (sleepiness in passive situations) was correlated with the ESS (beta = 1.65; 95%
      CI, 1.32 to 1.98; P < 0.001). Both ODSI 1 (beta = -0.15; 95% CI, -0.24 to -0.07;
      P < 0.001) and ODSI 2 (beta = -0.35; 95% CI, -0.55 to 0.16; P < 0.001) were
      significantly correlated with the FOSQ. CONCLUSION: The ODSI is a suitable
      measure of sleepiness and is appropriate for usage in clinical care in older
      adults.

PMID- 29033618
TI  - Schizophrenia and sleep disorders: links, risks, and management challenges.
AB  - Schizophrenia is a major psychiatric disorder that has a massive, long-lasting
      negative impact on the patients as well as society. While positive symptoms
      (i.e., delusions and hallucinations), negative symptoms (i.e., anhedonia, social
      withdrawal), and cognitive impairments are traditionally considered the most
      prominent features of this disorder, the role of sleep and sleep disturbances has
      gained increasing prominence in clinical practice. Indeed, the vast majority of
      patients with schizophrenia report sleep abnormalities, which tend to precede
      illness onset and can predict an acute exacerbation of psychotic symptoms.
      Furthermore, schizophrenia patients often have a comorbid sleep disorder,
      including insomnia, obstructive sleep apnea, restless leg syndrome, or periodic
      limb movement disorder. Despite accumulating data, the links between sleep
      disorders and schizophrenia have not been thoroughly examined, in part because
      they are difficult to disentangle, as numerous factors contribute to their
      comorbidity, including medication status. Additionally, sleep disorders are often
      not the primary focus of clinicians treating this population, despite studies
      suggesting that comorbid sleep disorders carry their own unique risks, including
      worsening of psychotic symptoms and poorer quality of life. There is also limited
      information about effective management strategies for schizophrenia patients
      affected by significant sleep disturbances and/or sleep disorders. To begin
      addressing these issues, the present review will systematically examine the
      literature on sleep disorders and schizophrenia, focusing on studies related to
      1) links between distinct sleep disorders and schizophrenia; 2) risks unique to
      patients with a comorbid sleep disorder; and 3) and management challenges and
      strategies.

PMID- 29033620
TI  - Comparative safety of intravenous Ferumoxytol versus Ferric Carboxymaltose for
      the Treatment of Iron Deficiency Anemia: rationale and study design of a
      randomized double-blind study with a focus on acute hypersensitivity reactions.
AB  - BACKGROUND: Intravenous (IV) iron is often used to treat iron deficiency anemia
      in patients who are unable to tolerate or are inadequately managed with oral
      iron. However, IV iron treatment has been associated with acute hypersensitivity
      reactions. The comparative risk of adverse events (AEs) with IV iron preparations
      has been assessed by a few randomized controlled trials, which are most often
      limited by small patient numbers, which lack statistical power to identify
      differences in low-frequency AE such as hypersensitivity reactions. MATERIALS AND
      METHODS: Ferumoxytol versus Ferric Carboxymaltose for the Treatment of Iron
      Deficiency Anemia (FIRM) is a randomized, double-blind, international,
      multicenter, Phase III study designed to compare the safety of ferumoxytol and
      ferric carboxymaltose (FCM). The study includes adults with hemoglobin <12.0 g/dL
      (females) or <14.0 g/dL (males), transferrin saturation <=20% or ferritin <=100
      ng/mL within 60 days of dosing, and a history of unsatisfactory or nontolerated
      oral iron therapy or in whom oral iron therapy is inappropriate. Patients are
      randomized (1:1) to ferumoxytol 510 mg or FCM 750 mg, each given intravenously on
      days 1 and 8. Primary end points are the incidence of moderate-to-severe
      hypersensitivity reactions, including anaphylaxis, and moderate-to-severe
      hypotension. All potential hypersensitivity and hypotensive reactions will be
      adjudicated by a blinded, independent Clinical Events Committee. A secondary
      safety end point is the composite frequency of moderate-to-severe
      hypersensitivity reactions, including anaphylaxis, serious cardiovascular events,
      and death. Secondary efficacy end points include mean change in hemoglobin and
      mean change in hemoglobin per milligram of iron administered from baseline to
      week 5. Urinary excretion of phosphorus and the occurrence of hypophosphatemia
      after IV iron administration will be examined as well as the mechanisms of such
      hypophosphatemia in a substudy. CONCLUSION: FIRM will provide data on the
      comparative safety of ferumoxytol and FCM, two IV iron preparations with similar
      dosing schedules, focusing on moderate-to-severe hypersensitivity reactions,
      including anaphylaxis, and moderate-to-severe hypotension. The study plans to
      enroll 2000 patients and is expected to complete in 2017.

PMID- 29033622
TI  - Changing physician perspectives on complementary and alternative medicine: the
      need for a top-down approach.

PMID- 29033621
TI  - Nonarteritic anterior ischemic optic neuropathy: cause, effect, and management.
AB  - Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common form
      of ischemic optic neuropathy and the second most common optic neuropathy.
      Patients are generally over the age of 50 years with vasculopathic risk factors
      (eg, diabetes mellitus, hypertension, and obstructive sleep apnea). The exact
      mechanism of NAION is not fully understood. In addition, several treatment
      options have been proposed. This article summarizes the current literature on the
      diagnosis, treatment, and management of NAION.

PMID- 29033623
TI  - Impact of supplemental training programs on improving medical students'
      confidence in providing diabetes self-management education and support.
AB  - BACKGROUND/PURPOSE: The purpose of this study was to evaluate the effectiveness
      of supplemental diabetes-related training modalities and volunteer activities in
      increasing first-year medical students' knowledge/comfort in providing diabetes
      self-management education and support (DSMES) to patients. METHODS: A group of
      medical students developed supplemental diabetes-related training/volunteer
      programs. The training modalities included an optional 7-session
      interprofessionally taught Diabetes Enrichment Elective and a 3-hour
      endocrinologist-led training session intended to prepare students for involvement
      in an inpatient DSMES volunteer program. The volunteer program provided the
      students with the opportunity to provide DSMES to patients with diabetes admitted
      to an academic medical center. Those participating in any of the stated programs
      were compared to those with no such training regarding confidence in providing
      DSMES using an optional online survey. The results were analyzed by using Mann
      Whitney U test and descriptive analyses. RESULTS: A total of 18 first-year
      medical students responded to the optional survey with a response rate of ~30%
      (10 of 33) among participants in any training/volunteer program. First-year
      medical students who attended any of the offered optional programs had
      statistically significant higher comfort level in 4 of the 6 areas assessed
      regarding providing DSMES compared with those with no such training (p<0.05),
      with medium to large effect size (r=0.48-0.59). CONCLUSION: This study suggests
      that the supplemental preclerkship diabetes-specific training
      modalities/volunteer programs can provide benefit in providing medical students
      with practical knowledge while improving their confidence in providing DSMES to
      patients with diabetes.

PMID- 29033624
TI  - Advances in medical education and practice: what millennial medical students say
      about flipped learning.

PMID- 29033625
TI  - The Salford Lung Study: a pioneering comparative effectiveness approach to COPD
      and asthma in clinical trials.
AB  - The Salford Lung Study (SLS) of patients with asthma and chronic obstructive
      pulmonary disease (COPD) is a practical, community-based, randomized, open-label
      pragmatic study on the efficacy and safety of the once-daily dry powder inhaler
      that combines the inhaled corticosteroid fluticasone furoate (FF) with the long
      acting beta2 agonist vilanterol (VI). The asthma component of the SLS is not yet
      reported but the COPD component, done over a 12-month period, found a
      statistically significant 8.4% reduction in COPD exacerbations when compared to
      usual care. No differences in adverse events, including serious adverse events
      and pneumonia, were noted. The importance of real-world findings, such as those
      found in the SLS COPD trial with inhaled FF/VI, is discussed in comparison to
      classical randomized controlled trials (RCTs) with inhaled FF/VI in COPD
      patients. The real-world, community-based pragmatic RCT like the SLS provides
      additional generalizable data with direct clinical applicability and potential
      usefulness in the development of practice guidelines. The results from the SLS,
      along with those of large and small RCTs, are supportive of the use of once-daily
      FF/VI in COPD maintenance therapy.

PMID- 29033626
TI  - The presence of obesity paradox in Greek patients with chronic heart failure.
AB  - PURPOSE: To investigate the effect of body mass index (BMI) values on 1- and 2
      year mortality rates in patients with chronic heart failure (HF). PATIENTS AND
      METHODS: We conducted a retrospective cohort study of 112 patients with confirmed
      HF who visited the HF outpatient unit of a tertiary hospital of Athens, Greece,
      during a 5-month period (December 2012 - April 2013). These patients were
      assigned to four groups based on their BMI category. Data collection was carried
      out through a review of the medical patient records and the filling in of a
      structured questionnaire, including information on the demographic and clinical
      patient variables. Additionally, 1- and 2-year patient mortality was recorded.
      The statistical significance was two-tailed, and p-values of less than 0.05 were
      considered significant. The statistical analysis was performed with Mann-Whitney
      U test, chi2 test, and Student's t-test using the SPSS software (IBM SPSS 21.0
      for Windows). RESULTS: Obese patients had significantly lower 1-year (13% vs
      34.6%, p=0.039) and 2-year (4% vs 21.4%, p=0.022) mortality rates compared with
      those with normal BMI values. Additionally, we found clinically and not
      statistically significant lower mortality in overweight and obese patients, when
      compared with normal BMI and overweight patients, respectively. CONCLUSION:
      Obesity paradox seems to be present in our study, translating to significantly
      lower long-term mortality rates of obese patients compared to those with normal
      BMI. The significantly higher left ventricular ejection fraction and hematocrit
      levels among obese HF patients could justify our study findings. Further research
      is needed due to the inherent weaknesses of BMI and the other study limitations.

PMID- 29033628
TI  - Neuro-Psycho-Behcet or Neuropsychiatric Behcet Disease: A Modified Name for an
      Old Disease.

PMID- 29033627
TI  - Impact of primary care exercise referral schemes on the health of patients with
      obesity.
AB  - Primary care exercise referral schemes (ERSs) are a potentially useful setting to
      promote physical activity (PA). It is not established, however, whether
      interventions to increase PA, such as ERSs, have differing health outcomes
      according to the participants' body mass index (BMI). This paper summarizes
      evidence for the impact of primary care ERSs on the health of people with obesity
      and reports findings of a reanalysis of the EMPOWER study, providing the first
      data to report differential outcomes of ERSs by BMI category. Our literature
      review revealed a paucity of published data. A 2011 Health Technology Assessment
      review and 2015 update were identified, but normal-weight participants were
      neither excluded nor were results stratified by weight in the included studies. A
      study of the effect of exercise referral in overweight women reported a
      significantly greater increase in PA levels in the ERS group than the control
      group at 3 months. Reanalysis of the EMPOWER study data showed a significant
      improvement in PA at 3 months in both obese and overweight/normal BMI groups,
      with the effect size attenuated to 6 months. There was no significant difference
      from baseline to 6 months in blood pressure for either BMI category. At 6 months,
      there was a significant decrease in weight from baseline for the obese category.
      Comparison of crude mean differences between BMI groups revealed a significant
      mean difference in PA at 3 months favoring the overweight/normal BMI group, but
      not at 6 months. There were no further significant differences in unadjusted or
      adjusted mean differences for other outcomes at follow-up. We report some
      evidence of a differential impact of ERS on PA by BMI category. However, the
      effect of ERSs in primary care for patients with obesity remains unclear due to
      the small number of published studies that have reported outcomes by BMI
      category. Further research is needed.

PMID- 29033629
TI  - Electroconvulsive Therapy in the Treatment of Mood Disorders: One-Year Follow-up.
AB  - INTRODUCTION: Electroconvulsive therapy (ECT) is known to be an effective option
      in the treatment of mood disorders, especially resistant depression. However, the
      remission achieved by ECT was reported to be not long lasting enough. The aim of
      the present study was to investigate the relapse/recurrence rates and associated
      risk factors during the first year after ECT in patients diagnosed with mood
      disorders. METHODS: In a naturalistic observation, patients diagnosed with
      unipolar depressive disorder or a depressive episode of bipolar disorder and who
      had achieved remission by ECT were followed up for at least one year. The
      patients were evaluated with structured interviews during the follow-up period.
      The relapse/recurrence rates were the primary outcome measurements, while
      hospitalization and suicide attempts were the secondary outcome measurements. The
      remitted and non-remitted patients were compared regarding the clinical features,
      ECT, and pharmacological variables. RESULTS: Fifty of 62 patients who had
      achieved remission with ECT completed the one year follow-up period. Thirty-three
      patients (66%) had relapse/recurrence, while 17 (34%) patients remained in
      remission. The relapse rates were similar in patients with unipolar depression
      and bipolar disorders. The mean number of ECT sessions was higher in relapsed
      patients with bipolar disorders. Multiple episodes were more frequent in non
      remitted patients with unipolar depression. Comorbid psychiatric diagnosis was
      higher in non-remitted patients with unipolar and bipolar disorders. CONCLUSION:
      The relapse/recurrence rate was found to be fairly high in the first year of
      follow-up in patients who had achieved remission with ECT. ECT decisions should
      be made carefully in patients with comorbid psychiatric diagnosis and multiple
      episodes as these are more risky. The ECT application procedure and successive
      maintenance treatment (maintenance ECT, pharmacotherapy, and psychotherapy)
      should be planned to sustain the remission for patients with mood disorders in
      long-term follow-up.

PMID- 29033630
TI  - Impact of Topiramate on Rat Phrenic Nerve-Hemidiaphragm Preparations.
AB  - INTRODUCTION: Topiramate has a negative modulatory effect on voltage-gated ion
      channels involved in neuromuscular junction transmission. To investigate the
      potential impact of topiramate on muscle contraction, phrenic nerve-hemidiaphragm
      preparations were used as a neuromuscular junction model. METHODS: Phrenic nerve
      hemidiaphragm preparations were isolated from rats and were mounted in oxygenated
      Krebs solution. Preparations were stimulated in the presence of topiramate and
      phenytoin with a rectangular pulse at 0.1 Hertz, 0.3 miliseconds, and 3
      miliseconds of duration, forming indirect, direct single, and tetanic muscle
      contractions, respectively. The expressed tension was isometrically recorded via
      a force displacement transducer on a polygraph. RESULTS: Topiramate and phenytoin
      directly and indirectly reduced contractions in a time-dependent manner. By
      contrast, topiramate, but not phenytoin, showed an excitatory effect on
      contraction in tetanic potentiation. CONCLUSION: To our knowledge, our study is
      the first to show the effects of topiramate on muscle contraction and
      neuromuscular junction transmission. Topiramate needs to be used with caution in
      patients with muscle weakness and respiratory problems.

PMID- 29033631
TI  - Validity and Reliability of the Turkish Version of the DSM-5 Posttraumatic Stress
      Symptom Severity Scale-Child Form.
AB  - INTRODUCTION: This study assessed the validity and reliability of the Turkish
      version of the DSM-5 Posttraumatic Stress Symptom Severity Scale-Child Form for
      use among the Turkish population. METHODS: The study group consisted of 30
      patients that had been treated in a child psychiatry unit and diagnosed with
      posttraumatic stress disorder and 83 healthy volunteers that were attending
      middle or high school during the study period. For reliability analyses, the
      internal consistency coefficient and the test-retest correlation coefficient were
      measured. For validity analyses, the exploratory factor analysis and correlation
      analysis with the Child Posttraumatic Stress Reaction Index for concurrent
      validity were measured. RESULTS: The Cronbach's alpha (the internal consistency
      coefficient) of the scale was 0.909, and the test-retest correlation coefficient
      was 0.663. One factor that could explain 58.5% of the variance was obtained and
      was congruent with the original construct of the scale. As for concurrent
      validity, the scale showed high correlation with the Child Posttraumatic Stress
      Reaction Index. CONCLUSION: It was concluded that the Turkish version of the DSM
      5 Posttraumatic Stress Symptom Severity Scale-Child Form can be used as a valid
      and reliable tool.

PMID- 29033632
TI  - Review of Viral Encephalitis Cases Seen at a Tertiary Care Center in Turkey:
      Focus on Herpes Simplex Type 1.
AB  - INTRODUCTION: The objective of this study was to determine the incidence of
      herpes simplex encephalitis (HSE), known as the most common, potentially mortal,
      and treatable cause of sporadic encephalitis, in a sample Turkish population.
      METHODS: The demographic, clinical, laboratory, imaging, electrophysiology, and
      polymerase chain reaction (PCR) DNA results of patients examined with a pre
      diagnosis of encephalitis were retrospectively examined. RESULTS: A total of 68
      patients were included in the study. The most common presenting symptom was
      altered behavior (67.6%), while temporal T2 hyperintensity was determined in the
      magnetic resonance imaging (MRI) of 27.9% of the patients and
      electroencephalography (EEG) abnormalities were determined in 66.2% of the
      patients. Lymphocytic pleocytosis was determined in the cerebrospinal fluid (CSF)
      in 35 patients. Fifty-seven patients had been diagnosed with viral encephalitis,
      3 with bacterial meningitis, 3 with tuberculous meningitis, 2 with sporadic
      Creutzfeld-Jakob disease, 2 with acute disseminating encephalomyelitis, and 1
      with Brucella encephalitis. Seven (10.2%) cases of viral encephalitis were found
      to be positive for herpes simplex virus (HSV) DNA by PCR. CONCLUSION: Viral
      encephalitis is the most common cause of infectious encephalitis; however, other
      atypical causes should also be noted. Negative PCR results for HSV DNA should not
      exclude the need for antiviral therapy in patients with a strong pre-diagnosis of
      HSE because diagnostic modalities, including PCR, may fail in acute settings and
      HSE remains the sole treatable cause of infectious encephalitis.

PMID- 29033633
TI  - Measuring Alexithymia via Trait Approach-I: A Alexithymia Scale Item Selection
      and Formation of Factor Structure.
AB  - INTRODUCTION: It is not clear in the literature whether available instruments are
      sufficient to measure alexithymia because of its theoretical structure. Moreover,
      it has been reported that several measuring instruments are needed to measure
      this construct, and all the instruments have different error sources. The old and
      the new forms of Toronto Alexithymia Scale are the only instruments available in
      Turkish. Thus, the purpose of this study was to develop a new scale to measure
      alexithymia, selecting items and constructing the factor structure. METHODS: A
      total of 1117 patients aged from 19 to 82 years (mean = 35.05 years) were
      included. A 100-item pool was prepared and applied to 628 women and 489 men. Data
      were analyzed using Explanatory Factor Analysis, Confirmatory Factor Analysis,
      and Item Response Theory and 28 items were selected. The new form of 28 items was
      applied to 415 university students, including 271 women and 144 men aged from 18
      to 30 (mean=21.44). RESULTS: The results of Explanatory Factor Analysis revealed
      a five-factor construct of "Solving and Expressing Affective Experiences,"
      "External Locused Cognitive Style," "Tendency to Somatize Affections," "Imaginary
      Life and Visualization," and "Acting Impulsively," along with a two-factor
      construct representing the "Affective" and "Cognitive" components. All the
      components of the construct showed good model fit and high internal consistency.
      The new form was tested in terms of internal consistency, test-retest
      reliability, and concurrent validity using Toronto Alexithymia Scale as criteria
      and discriminative validity using Five-Factor Personality Inventory Short Form.
      CONCLUSION: The results showed that the new scale met the basic psychometric
      requirements. Results have been discussed in line with related studies.

PMID- 29033634
TI  - Sudden Unexpected Death in Epilepsy: A Retrospective Autopsy Study of 112
      Epileptic Patients.
AB  - INTRODUCTION: Sudden unexpected deaths comprise the most important and worthy
      investigation case profiles in both neurology and forensic medicine. Epilepsy,
      which is one of the neuropathological causes of sudden unexpected deaths, is an
      important disorder having mysterious aspects. The aim of this study is to make
      common the points of view between neurology and forensic medicine experts and to
      discuss the features of the findings together with the related clinical
      hypotheses, leading to the differential diagnosis of sudden unexpected death in
      epilepsy (SUDEP) by presenting autopsy findings and available medical data of
      patients who had a prior diagnosis of epilepsy. METHODS: In Istanbul, the cases
      of 20334 autopsied patients who were referred to The Ministry of Justice Council
      of Forensic Medicine between 2007 and 2011 were identified from the complete
      forensic autopsy data of the city and were retrospectively reviewed. Patients who
      had a prior diagnosis of epilepsy were included. Both descriptive and inferential
      statistical analyses were performed through the parameters of demographical data,
      physical properties, incident features, macroscopic-microscopic autopsy findings,
      and cause of death initially for all cases and then separately for SUDEP cases.
      RESULTS: Among the 20334 patients, 112 were determined to have a prior diagnosis
      of epilepsy. A possible macroscopic and/or microscopic epileptic focus was
      present in 23 (20.5%) of these 112 cases. The cause of death was determined to be
      SUDEP in 40 (35.7%) cases, while it could not be determined in 28 (25%) cases.
      Among patients whose death cause was considered as SUDEP, the male-to-female
      ratio was 1.1:1, while the mean age was 31.5+/-13.9 years in males and 29.6+/
      12.9 years in females. The presence of hypertrophy and myocardial scar tissue
      findings in the microscopic examination were significantly more frequent among
      patients determined to have died from cardiovascular diseases compared to
      patients in the SUDEP group (p=0.001 for each finding). Besides, in 40 SUDEP
      cases, 38 (95%) patients underwent toxicological analysis and no antiepileptic
      agent was detected in 21 (55.3%) of these. CONCLUSION: It can be concluded that
      there is equality in gender distribution among SUDEP patients, that the young
      adult population has a slightly increased risk for SUDEP, and that the
      inconsistent use of antiepileptic medicines is a greater risk factor for SUDEP
      than polytherapy. Besides, it is important to emphasize that all clinical and
      postmortem parameters together should be considered for the differential
      diagnosis of SUDEP, particularly with cardiovascular diseases.

PMID- 29033635
TI  - Evaluation of 5-HTTLPR Gene Polymorphism and Resilience Components on the
      Development of Psychopathology in Adolescent Sexual Abuse Cases.
AB  - INTRODUCTION: More than one-fourth adolescents are exposed to unexpected
      frightening experiences and traumas until adulthood. In this study, we aimed to
      determine the potential role of serotonin transporter (5-HTT) gene polymorphism
      regarding resilience factors in the symptom variability of individuals exposed to
      sexual abuse. METHODS: Adolescents aged 11-17 years, who were admitted to the
      Marmara University Child Psychiatry Outpatient Clinic Forensic division with
      sexual abuse experience history, were informed about the research, and volunteers
      were included in the study. Turkish versions of "Kiddie-Schedule for Affective
      Disorders and Schizophrenia-Present and Lifetime (K-SADS-PL)" was used to assess
      the psychopathology and functionality. The evaluation of participants also
      included self-reports based on "Eysenck Personality Inventory" and "Ways of
      Coping Inventory" for reflecting the resilience domain. RESULTS: The sample
      included 16 girls (88.9%) and 2 boys (11.1%), and the mean (+/-standard
      deviation) age was 14.58+/-1.97 years. Genotyping of the insertion/deletion
      polymorphism (5-HTTLPR) in the 5-HTT gene's transcriptional control zone was
      established, and 8 participants (44.4%) were determined to be of the LL genotype,
      while 7 (38.8%) were LS and 3 (16.6%) were SS carriers. Considering the
      relationship between coping styles regarding resilience and genetic variants,
      87.5% of participants (n=7) exhibiting problem-focused coping style were
      determined found to carry the LL allele, while 90% (n=9) who exhibited emotion
      focused coping styles were the SS-LS allele carriers (p=0.003). CONCLUSION: Our
      findings suggest that 5-HTTLPR gene polymorphism has a significant impact on the
      formation of coping styles. More studies are needed to determine other factors
      involved in the complex relationship between 5-HTTLPR gene polymorphism and
      development of psychopathology.

PMID- 29033636
TI  - Validity and Reliability of the Quality of Life in Epilepsy Inventory (QOLIE-10)
      For Turkey.
AB  - INTRODUCTION: The purpose of this study was to test as a shortened form of the
      health-related quality of life for patients with epilepsy inventory (QOLIE).
      METHODS: A study of 148 adult epileptic patients admitted to the Neurology
      Outpatient Clinic at Cumhuriyet University Hospital in Sivas was used to derive a
      brief screening tool from a longer instrument (QOLIE-31). RESULTS: The 10-item
      questionnaire (QOLIE-10) contains general and epilepsy-specific dimensions
      grouped into three domains: Epilepsy Effects (memory, physical effects, and
      mental effects of medication), Mental Health (energy, depression, overall quality
      of life), and Role Functioning (seizure worry, work, driving, social limits).
      Cronbach's alpha (measure of internal consistency) was high, as were the
      associations between QOLIE-10 and the Nottingham Health Profile (NHP). High
      correlations between QOLIE-10 and NHP domains (emotional reactions, energy,
      physical mobility, and social isolation) were found. CONCLUSION: The QOLIE-10
      questionnaire is considered to be a valid and reliable tool for use in Turkey.
      Health professionals are encouraged to use this questionnaire to routinely
      examine the influences of the disease process in epilepsy patients.

PMID- 29033637
TI  - Cognitive Functioning in Euthymic Bipolar Patients on Monotherapy with Novel
      Antipsychotics or Mood Stabilizers.
AB  - INTRODUCTION: Bipolar disorder is associated with cognitive dysfunction in
      several domains. Medication effect is a potential confounder that can only be
      statistically controlled in many studies. The cognitive profile in bipolar
      disorder during remission on maintenance antipsychotics or mood stabilizers
      medication has not been compared before. METHODS: We compared the cognitive
      profile of bipolar disorder patients euthymic for 2 month or more on monotherapy
      with novel antipsychotics (AP) (n=16), lithium carbonate (Li) (n=25) or valproic
      acid (VPA; n=26). Forty-two individuals were assessed as controls. The cognitive
      battery included Wechsler Adult Intelligence Scale-Revised (WAIS-R) subtests, the
      Wechsler Memory Scale (WMS), and Wisconsin Card Sorting Test (WCST). RESULTS: All
      three patient groups compared to controls performed poorly on the working memory
      and verbal memory tasks (F=3.59, df=3, p=0.02 for WAIS-R Arithmetic and F=123.64,
      df=3, p<0.01 for WMS Logical Memory). The differences remained significant after
      controlling for age. Across patients, the only significant difference was between
      the Li and AP groups in terms of working memory. The Li group performed better
      (F=3.59, df=2, p=0.02) and the difference survived correction for age and
      clinical features. CONCLUSIONS: The findings of this study suggest that working
      memory impairment in bipolar patients on monotherapy with atypical AP, whereas
      verbal memory impairment might be related to bipolar disorder itself. Working
      memory might be a state marker, whereas verbal memory could be a trait marker of
      bipolar disorder. Atypical AP might have an adverse effect on cognition in
      bipolar disorder. These findings cannot be generalized to all bipolar patients,
      particularly the poor responders to monotherapy.

PMID- 29033638
TI  - Tolosa-Hunt Syndrome - Cranial Neuroimaging Findings.
AB  - INTRODUCTION: The etiology of Tolosa-Hunt Syndrome (THS) is still unknown. The
      initial standard magnetic resonance imaging (MRI) may not be sufficient for
      diagnosis, so dynamic contrast-enhanced MRI may be necessary to demonstrate the
      presence of lesions. METHODS: Seven patients diagnosed with THS according to the
      International Headache Society criteria (beta version) were included into the
      study. Patients were assessed in terms of type, age, symptoms and findings,
      accompanying disease, localization of the determined lesion, response to
      treatment, and clinical progress. The "Tolosa-Hunt protocol" was applied in all
      patients, and the cavernous sinuses, orbital apices, and orbits were evaluated.
      The parameters used for the patients were as follows: Turbospin echo T1 and T2
      weighted sequences on the axial plane, turbospin echo fat-saturated T2 weighted
      sequence on the coronal plane, turbospin echo T2 weighted sequence on the
      sagittal plane, spin echo fat-saturated T1 sequences repeated on the axial and
      coronal planes followed by intravenous administration of gadolinium. In all
      sequences the slice thickness was 3 mm. RESULTS: Four of seven cases diagnosed
      with THS were males, and the average age of the patients was 45.7+/-18.1 years
      (range 25-69 years). A follow-up MRI in patient 5 after three months showed
      decreased signal intensity and enhancement of the affected cavernous sinus.
      CONCLUSION: Conventional MRI may be insufficient to show the granulomatous
      inflammation, and an MRI method referred to as the Tolosa-Hunt protocol should be
      applied to those who are thought to have THS.

PMID- 29033639
TI  - A Survey Focusing on Lucid Dreaming, Metacognition, and Dream Anxiety in Medical
      Students.
AB  - INTRODUCTION: The aim of this study was to examine the level of lucidity and its
      relation with metacognitive beliefs and dream anxiety in medical students.
      METHODS: Nine hundred sixteen medical students were enrolled in the study. The
      participants were assessed with the Lucidity and Consciousness in Dreams Scale
      (LuCiD), the Metacognition Questionnaire-30 (MCQ-30), and the Van Dream Anxiety
      Scale (VDAS). RESULTS: There was no significant difference in mean total lucidity
      score between females and males, but there were some significant sex differences
      in subscales of lucidity, and control was significantly higher in male students,
      while realism, thought, and dissociation were significantly higher in female
      students. In addition, females had more dream anxiety levels, higher total MCQ-30
      scores, and higher cognitive confidence and uncontrollability scores according to
      Metacognition Questionnaire-30 than males. We also found that the mean lucidity
      level was positively correlated with the mean total metacognition score and the
      mean total dream anxiety level. DISCUSSION: Our results suggest that female
      medical students tend to have more realistic dreams (p=0.018), have more logical
      thoughts during dreaming (p=0.011), and have a more dissociative experience
      during dreaming (p=0.028), while male medical students have more controlled dream
      events (p=0.002). There seem to be differences according to lucidity features
      between sexes, and the relationship between subdomains of lucidity and
      metacognition might lead to new therapeutic approaches to several psychiatric
      disorders such as anxiety disorders.

PMID- 29033640
TI  - Identification of Allodynic Migraine Patients with the Turkish Version of the
      Allodynia Symptom Checklist: Reliability and Consistency Study.
AB  - INTRODUCTION: Cutaneous allodynia is regarded as an expression of central
      sensitization in migraine. Although the gold standard is quantitative sensory
      testing, several practical assessment questionnaires have been developed to
      assess allodynia in migraine. We aimed to establish the first valid Turkish
      allodynia assessment questionnaire based on a 12-item allodynia symptom checklist
      and to evaluate the associated factors. METHODS: The first part of the study
      included the translation and cultural adaptation of a Turkish version of the
      checklist. The Turkish version of the questionnaire was administered to 344
      episodic and chronic migraine patients, who were chosen according to the
      International Classification of Headache Disorders -III beta criteria. RESULTS:
      The total checklist score showed excellent test-retest reliability (r=0.821). The
      internal consistency of the checklist was assessed using Cronbach alpha values
      and was found to be acceptable (Cronbach alpha for the checklist=0.767). Data
      analysis revealed that 10 items of the questionnaire adequately identified
      allodynic subjects. Cutaneous allodynia was present in 218 (63.4%) migraine
      patients. Allodynia was more prominent in patients experiencing migraine with
      aura (p=0.008) and in females (p<0.001). Multiple logistic regression analysis
      found that female gender, aura existence, longer headache duration, and higher
      attack frequency were the major determinants of cutaneous allodynia. CONCLUSION:
      Allodynia is common and has clinical significance in migraine; therefore,
      establishing a validated Turkish questionnaire for the assessment of allodynia
      was necessary. In this study, a Turkish version of the allodynia symptom
      checklist was validated and found to be convenient for the identification of
      allodynia in migraine patients.

PMID- 29033641
TI  - Do Low Serum UCH-L1 and TDP-43 Levels Indicate Disturbed Ubiquitin-Proteosome
      System in Autism Spectrum Disorder?
AB  - INTRODUCTION: The mechanism of ubiquitination-related abnormalities causing
      neural development problems is still unclear. We examined the association between
      autism and serum transactive response DNA-binding protein-43 (TDP-43) and
      ubiquitin c-terminal hydrolase-L1 (UCH-L1) levels, both of which are members of
      the ubiquitin-proteosome system. METHODS: We measured serum levels of TDP-43 and
      UCH-L1 in 24 children with autism and 24 healthy children. Childhood Autism
      Rating Scale (CARS) was used to assess symptom severity at admission. RESULTS:
      The mean serum TDP-43 and UCH-L1 levels in children with autism spectrum disorder
      (ASD) were found to decrease compared to healthy controls (p<0.001, 506.21+/
      780.97 ng/L and 1245.80+/-996.76 ng/L, respectively; 3.08+/-5.44 ng/mL and 8.64+/
      6.67 ng/mL, respectively). A positive correlation between serum TDP-43 levels and
      UCH-L1 levels was found in the ASD group (r=0.947, n=24, p<0.001). The CARS score
      of children with ASD was 48.91 points (standard deviation [SD]: 5.82).
      CONCLUSION: Low serum levels of UCH-L1 and TDP-43 may reflect disturbed
      ubiquitination in autism.

PMID- 29033642
TI  - The Effect of Type D Personality on Quality of Life in Patients with Multiple
      Sclerosis.
AB  - INTRODUCTION: The Type D personality was reported as an important indicator of
      adverse clinical outcomes and quality of life in various diseases. The objective
      of this study was to investigate the relationships between the Type D personality
      and clinical features and the effect of Type D personality on quality of life in
      patients with multiple sclerosis (MS). METHODS: Seventy-four patients with MS
      participated in this study. Clinical parameters of the patients were recorded and
      disability was assessed using the Expanded Disability Status Scale (EDSS).
      Patients were examined with the Beck Depression Inventory (BDI), Beck Anxiety
      Inventory (BAI), Type D Scale (DS14), and 36-Item Short-Form Health Survey (SF
      36). RESULTS: BDI and BAI scores were significantly higher and mental subscale of
      the SF-36 scores were significantly lower in Type D compared to nonType D
      (p<0.001, p=0.001, and p<0.001, respectively). The total DS14 scores were found
      to be positively correlated with EDSS, BDI, and BAI and negatively correlated
      with SF-36 mental subscale (p=0.02, p<0.001, p<0.001, and p<0.001, respectively).
      Multivariate linear regression analysis indicated that the total DS14 score was
      independently associated with the mental component of SF-36 (p<0.001).
      CONCLUSION: The Type D personality traits may worsen the quality of life,
      particularly the mental component, in patients with MS. Consequently, the
      assessment of MS patients by brief and valid DS14 may be valuable for clinical
      practice.

PMID- 29033643
TI  - Dandy-Walker Malformation Presenting with Affective Symptoms.
AB  - Dandy-Walker malformation is defined by enlarged posterior fossa, cystic
      dilatation of the fourth ventricle, and cerebellar hypoplasia. Although
      developmental delay and mental retardation are common in Dandy-Walker
      malformation cases, other comorbid psychiatric conditions have been rarely
      reported. There are limited numbers of case reports about comorbidity of bipolar
      disorder with Dandy-Walker malformation in the literature. Herein, a Dandy-Walker
      malformation case presenting affective symptoms is reported, and psychiatric
      symptoms which might be seen in this rare malformation are discussed along with
      diagnosis, treatment, and follow-up processes. A 27-year-old male patient,
      hospitalized for compulsory treatment, had been diagnosed with Dandy-Walker
      malformation in childhood. First complaints were attention deficiency, behavioral
      problems, learning difficulties; and manic and depressive episodes have occurred
      during follow-ups. He recently complained of decreased need for sleep,
      irritability, and increased speed of thought, and psychiatric examination was
      consistent with manic episode. Cranial computed tomography (CT) revealed
      bilateral ventriculomegaly, enlarged third and fourth ventricles with posterior
      fossa cyst, and cerebellar hypoplasia. His treatment included 30 mg/day
      aripiprazole, 1000 mg/day valproic acid, 200 mg/day quetiapine, 4 mg/day
      biperiden, and 100 mg/month paliperidone palmitate. Beside its traditional role
      in the regulation of coordination and motor functions, cerebellum is increasingly
      emphasized for its involvement in the mood regulation. Thus, as seen in Dandy
      Walker malformation, cerebellar anomalies are suggested to play a role in the
      pathophysiology of mood disorders. Further studies are needed to better
      understand the relationship between mood disorders and cerebellum. Moreover,
      treatment options should be considered carefully in terms of resistance to
      treatment and potential side effects, for psychiatric disorders occurring in
      these cases; and detailed examinations, including cranial imaging, would be
      beneficial in bipolar cases with early onset, unresponsiveness to treatment,
      presenting atypical symptoms, mental retardation, and developmental delay as well
      as neurological symptoms and signs.

PMID- 29033644
TI  - A Very Rare Type of Neuralgia: Nervus Intermedius Neuralgia.

PMID- 29033645
TI  - Kleine-Levine Syndrome Co-occuring with Bipolar Disorder.

PMID- 29033646
TI  - Cerebrovascular Events Secondary to Pulmonary Arteriovenous Malformation Based on
      Genetic Heterogeneity.

PMID- 29033647
TI  - Erratum.
AB  - [This corrects the article on p. 169 in vol. 53, PMID: 28360791.].

PMID- 29033648
TI  - Recircumscription and taxonomic revision of Siderasis, with comments on the
      systematics of subtribe Dichorisandrinae (Commelinaceae).
AB  - A new circumscription and a total of six microendemic species, four of them new
      to science, are herein presented for Siderasis, based on field and herbaria
      studies, and cultivated material. We provide an identification key to the species
      and a distribution map, description, comments, conservation assessment, and
      illustration for each species. Also, we present an emended key to the genera of
      subtribe Dichorisandrinae, and comments on the morphology and systematics of the
      subtribe.

PMID- 29033649
TI  - Study of the leaf anatomy in cross-section in the Iberian species of Festuca L.
      (Poaceae) and its systematic significance.
AB  - A study of the leaf anatomy in the species of the genus Festuca present in the
      Iberian Peninsula was made. A total of 68 taxa were included and 15 characters
      were measured in leaf cross-section. The major anatomical features of each
      taxonomic group were characterized, and some variability was observed in the
      taxa. The anatomical patterns observed were compared and discussed with the
      relationships suggested by the molecular analyses. The leaf outline, the presence
      or absence of complete girders, and the development degree of the bulliform cells
      were the main characters to differentiate among fescue species of the fine-leaved
      clade and those of the broad-leaved clade. The most useful character to segregate
      species groups within the different taxonomic sections was the arrangement of the
      sclerenchyma, and a remarkable variability of this character was found in the
      species of Festuca section Festuca, especially in those located in other lineages
      according to molecular markers. Most of the anatomical patterns were not
      exclusive of the sections or lineages, and only some taxa could be anatomically
      differentiated at species level based on a set of non-taxative characters. The
      discordant pattern observed in F. henriquesii, a species traditionally included
      in Festuca sect. Festuca that shared anatomical features with the species of "F.
      rubra complex", suggests its possible inclusion in the sect. Aulaxyper pending
      further taxonomic and phylogenetic analyses.

PMID- 29033650
TI  - Stipa pennata subsp. ceynowae (Poaceae, Pooideae), a new taxon from Central
      Europe.
AB  - Based on numerical analyses of macromorphological characters, scanning electron
      microscopy observation of leaves and lemma micromorphology, as well as field
      observations, Stipa pennata subsp. ceynowae was described here as a new taxon
      from Poland. It differs from the most similar S. pennata subsp. pennata and S.
      borysthenica mainly by its longer ligules of vegetative shoots. The affinities of
      this taxon are discussed and a morphological comparison with related species is
      provided. Illustrations and images of the micromorphological structures, as well
      as information about its distribution, habitat and conservation status are given.

PMID- 29033651
TI  - Premna bhamoensis (Lamiaceae, Premnoideae), a new species from Kachin State,
      northeastern Myanmar.
AB  - In the present study, we describe and illustrate a new species, Premna bhamoensis
      Y. T. Tan & B. Li (Lamiaceae), from Myanmar. In the 1980s, this species was
      transplanted from Bhamo County in northeastern Myanmar to the Xishuangbanna
      Tropical Botanical Garden, Chinese Academy of Sciences. The species shows
      striking morphological similarity to P. menglaensis B. Li, and thus, has been
      misidentified as the latter for a long period of time. However, morphological
      comparison revealed that P. bhamoensis is distinct from P. menglaensis in many
      aspects. Moreover, literature survey and specimen examinations also indicated
      that P. bhamoensis is undoubtedly different from all seven known congenetic
      species recorded from Kachin State, Myanmar, and a key for their identification
      has been provided in this paper.

PMID- 29033653
TI  - Melicope stonei, section Pelea (Rutaceae), a new species from Kaua'i, Hawaiian
      Islands: with notes on its distribution, ecology, conservation status, and
      phylogenetic placement.
AB  - Melicope stonei K.R. Wood, Appelhans & W.L. Wagner (section Pelea, Rutaceae), a
      new endemic tree species from Kaua'i, Hawaiian Islands, is described and
      illustrated with notes on its distribution, ecology, conservation status, and
      phylogenetic placement. The new species differs from its Hawaiian congeners by
      its unique combination of distinct carpels and ramiflorous inflorescences arising
      on stems below the leaves; plants monoecious; leaf blades (5-)8-30 * (4-)6-11 cm,
      with abaxial surface densely tomentose, especially along midribs; and very long
      petioles of up to 9 cm. Since its discovery in 1988, 94 individuals have been
      documented and are confined to a 1.5 km2 region of unique high canopy mesic
      forest. Melicope stonei represents a new Critically Endangered (CR) single island
      endemic species on Kaua'i.

PMID- 29033652
TI  - Craterispermum capitatum and C. gabonicum (Rubiaceae): two new species from the
      Lower Guinean and Congolian Domains.
AB  - Craterispermum capitatum and C. gabonicum, two new species of Rubiaceae, are
      described from the Lower Guinea and Congolian Domains. Detailed descriptions and
      distribution maps are provided for each species, their conservation status is
      assessed and their taxonomic affinities are discussed. Craterispermum gabonicum
      is unique within the genus because of the strong dimorphism in brevistylous and
      longistylous flowers and inflorescences. We hypothesize that this species shows
      some form of dioecy. The distribution of C. capitatum shows a wide disjunction:
      the species is present in the Lower Guinean and Congolian Domains but absent from
      Gabon and South Cameroon. An identification key for the Craterispermum species
      present in the Lower Guinean and Congolian Domains is given.

PMID- 29033654
TI  - A revision of the Solanum elaeagnifolium clade (Elaeagnifolium clade; subgenus
      Leptostemonum, Solanaceae).
AB  - The Solanum elaeagnifolium clade (Elaeagnifolium clade) contains five species of
      small, often rhizomatous, shrubs from deserts and dry forests in North and South
      America. Members of the clade were previously classified in sections Leprophora,
      Nycterium and Lathyrocarpum, and were not thought to be closely related. The
      group is sister to the species-rich monophyletic Old World clade of spiny
      solanums. The species of the group have an amphitropical distribution, with three
      species in Mexico and the southwestern United States and three species in
      Argentina. Solanum elaeagnifolium occurs in both North and South America, and is
      a noxious invasive weed in dry areas worldwide. Members of the group are highly
      variable morphologically, and this variability has led to much synonymy,
      particularly in the widespread S. elaeagnifolium. We here review the taxonomic
      history, morphology, relationships and ecology of these species and provide keys
      for their identification, descriptions, full synonymy (including designations of
      lectotypes) and nomenclatural notes. Illustrations, distribution maps and
      preliminary conservation assessments are provided for all species.

PMID- 29033655
TI  - Waarnemingen.be - Plant occurrences in Flanders and the Brussels Capital Region,
      Belgium.
AB  - Waarnemingen.be - Plant occurrences in Flanders and the Brussels Capital Region,
      Belgium is a species occurrence dataset published by Natuurpunt. The dataset
      contains almost 1.2 million plant occurrences of 1,222 native vascular plant
      species, mostly recorded by volunteers (citizen scientists), mainly since 2008.
      The occurrences are derived from the database http://www.waarnemingen.be, hosted
      by Stichting Natuurinformatie and managed by the nature conservation NGO
      Natuurpunt. Together with the datasets Florabank1 (Van Landuyt and Brosens 2017)
      and the Belgian IFBL (Instituut voor Floristiek van Belgie en Luxemburg) Flora
      Checklists (Van Landuyt and Noe 2015), the dataset represents the most complete
      overview of indigenous plants in Flanders and the Brussels Capital Region.

PMID- 29033656
TI  - Typifications for Galactia purshii and G. volubilis (Fabaceae).
AB  - The pervasive difficulties encountered with studying Galactia in the eastern USA
      necessitate additional typifications to stabilize the taxonomy. Galactia purshii
      is lectotypified here as the earliest available but overlooked name for a fairly
      common species of the Atlantic Coast and peninsular Florida. Galactia volubilis
      is epitypified here since the characterization of the species has been limited by
      its lectotype being an illustration. A lectotype is designated for Galactia
      pilosa var. angustifolia, a form with narrow leaves here considered synonymous
      with G. volubilis.

PMID- 29033657
TI  - A new combination and taxonomic notes in Pseudobombax Dugand (Malvaceae).
AB  - Taxonomic notes in the Neotropical genus Pseudobombax (Malvaceae) are presented.
      One new combination and two new heterotypic synonyms for taxa originally
      described from Brazil and Ecuador are proposed based on both morphological and
      previously published molecular evidence. The taxonomic changes will be adopted in
      a treatment of Pseudobombax for the upcoming Brazilian Flora 2020 and in a
      forthcoming revision of the genus throughout its range.

PMID- 29033658
TI  - A new species of Saracha (Solanaceae) from the Central Andes of Peru.
AB  - Saracha andina Rob. Fernandez, I. Revilla & E. Pariente, sp. nov. (Solanaceae), a
      new species endemic to the central Andes of Peru, is described here. The new
      species differs from other species of Saracha Ruiz & Pav. by the combination of
      small and coriaceous leaves and clearly tubular flowers. A summary of the
      taxonomic history of the genus Saracha, an identification key for its species and
      a phylogenetic analysis of this genus and related genera are provided.

PMID- 29033659
TI  - Eithea lagopaivae, a new critically endangered species in the previously
      monotypic genus Eithea Ravenna (Amaryllidaceae).
AB  - Eithea lagopaivae Campos-Rocha & Dutilh, sp. nov. is described as the second
      species of the formerly monotypic genus Eithea. It is characterized by a one
      flowered inflorescence, completely hollow scape, white or lightly magenta
      striated flower that is enclosed by spathe bracts fused for more than the lower
      fifth of its length. Comments on its range, habitat, phenology, as well as
      photographs and illustrations are provided. In addition, a distribution map and
      an identification key for the two species of the genus are presented and
      anatomical and ecological differences compared. Known by only two small
      populations exposed to several types of threats and without any guarantee of
      protection, E. lagopaivae is considered a Critically Endangered (CR) species.

PMID- 29033660
TI  - Gelidocalamus xunwuensis (Poaceae, Bambusoideae), a new species from southeastern
      Jiangxi, China.
AB  - Gelidocalamus xunwuensis W.G.Zhang & G.Y.Yang, a new species collected from Xunwu
      County of Jiangxi Province in China, is described and illustrated. The new
      species is similar to G. stellatus in the habit, but differs by internodes
      sparsely hairy with granuliferous warts, culm sheath stiffly hairy, culm sheath
      blade broadly lanceolate to narrowly triangular, each node with a ring of
      appressed trichomes below, foliage leaves broadly lanceolate to narrowly oblong,
      and new shoots occurring in late October.

PMID- 29033661
TI  - Incadendron : a new genus of Euphorbiaceae tribe Hippomaneae from the sub-Andean
      cordilleras of Ecuador and Peru.
AB  - Incadendron esseri K.Wurdack & Farfan, gen. & sp. nov., from the wet sub-Andean
      cordilleras of Ecuador (Cordillera del Condor) and Peru (Cusco, Oxapampa) is
      described and illustrated. This recently discovered large canopy tree with a
      narrow elevational range presents an unusual combination of rare morphological
      characters in Hippomaneae including mucilage-secreting sheathing stipules,
      conduplicate ptyxis, and large, woody fruits. The broader significance of these
      characters in Hippomaneae is discussed. The morphology and anatomy of Incadendron
      were investigated, highlighting its fruit similarities with Guiana Shield endemic
      Senefelderopsis, and the systematics value of ptyxis variation, which remains
      poorly studied for the family.

PMID- 29033662
TI  - A valid name for the Xishuangbanna gourd, a cucumber with carotene-rich fruits.
AB  - Herbarium specimens deposited in publicly accessible collections are the basis
      for all scientific names because only permanent specimens can be re-studied by
      independent researchers, the very essence of science. Re-investigations may be
      done with morphological, chemical, genomic, computer-tomographic, or other
      methods. Based on new herbarium material, I here provide a name for the
      Xishuangbanna gourd, a plant long cultivated in Yunnan because of its large non
      bitter fruits, rich in beta-carotene. Genome re-sequencing of numerous accessions
      has shown that this cucumber mutant is closer to Cucumis sativus var. sativus
      than is the wild bitter-fruited progenitor C. sativus var. hardwickii, and two
      dozen studies have further clarified the genetics of key traits, including pulp
      color, fruit shape, and flowering times. Morphological and molecular diagnoses of
      the new variety are provided and museum-quality specimens have been distributed
      to the World's major herbaria.

PMID- 29033663
TI  - Pteris latipinna sp. nov. (Pteridaceae), a new species segregated from Pteris
      fauriei.
AB  - Pteris fauriei is widely distributed in Eastern Asia and has high morphological
      variation. Some morphologically similar plants related to this species are
      difficult to distinguish. We showed that the new Pteris species from Taiwan,
      previously identified as P. fauriei, can be morphologically distinguished by its
      wide pinnae, larger terminal pinnae than the lateral pinnae in sterile fronds,
      and triangular basal segments of the lateral pinnae. It was confirmed that this
      species is phylogenetically separated from the other East Asian Pteris species,
      except for a morphologically distinct species P. arisanensis, by means of
      chloroplast genes, rbcL and matK. The new species is named as Pteris latipinnasp.
      nov., referring to its wide pinnae. Here, we provide a key to facilitate the
      identification of the morphologically similar Pteris species in Asia. The
      morphological descriptions, images, ecology, and distribution are also presented.

PMID- 29033664
TI  - Bituminaria antiatlantica (Psoraleeae, Fabaceae), a new species from Morocco.
AB  - A new species of Bituminaria is described and illustrated: Bituminaria
      antiatlantica Brullo, C. Brullo, Cambria, Cristaudo & Giusso, sp. nov., which is
      endemic to Anti-Atlas Mountains (Morocco). It is a true chasmophyte,
      characterized by a suffruticose habit, several woody branches, leaflets
      coriaceous, rounded to ovate, small, few-flowered inflorescences and corolla pale
      coloured.

PMID- 29033665
TI  - The Shenzhen Declaration on Plant Sciences: Too late or just in time?

PMID- 29033666
TI  - The Shenzhen Declaration on Plant Sciences - Uniting plant sciences and society
      to build a green, sustainable Earth.

PMID- 29033667
TI  - On merging Acer sections Rubra and Hyptiocarpa: Molecular and morphological
      evidence.
AB  - In this study, we expanded Acer sect. Rubra Pax to include A. sect. Hyptiocarpa
      Fang. Traditionally, section Rubra comprises two iconic species, Acer rubrum
      Linnaeus (red maple) and A. saccharinum Linnaeus (silver maple), of eastern North
      American forests as well as the rare Japanese montane species, A. pycnanthum K.
      Koch. Section Hyptiocarpa consists of A. laurinum Hasskarl and A. pinnatinervium
      Merrill, which occur in subtropical and tropical regions of southwestern China to
      southeast Asia. Here, we confirm prior phylogenetic results showing the close
      relationship between sects. Rubra and Hyptiocarpa, and we use scanning electron
      microscopy to demonstrate that leaves of species within these sections have
      similar arrangements of cuticular waxes, which account for the silvery color of
      their abaxial surfaces. We describe that the sections also share labile sex
      expression; inflorescences that range from compound racemose thyrses, to racemes
      or umbels and that may have undergone evolutionary reduction; and several
      features of their fruits, such as seed locules without keels, basal portion of
      wings straight, acute attachment angle between mericarps, and production of some
      mericarps that are seedless and partially developed at maturity. Our expansion of
      sect. Rubra to include sect. Hyptiocarpa better elucidates the biogeographic and
      evolutionary history of these species. Additionally, we show that A. laurinum and
      A. pinnatinervium have intergrading morphology and are probably synonymous, but
      we note that further studies are required to conclude their taxonomic status.

PMID- 29033668
TI  - Integrative research identifies 71 new plant species records in the state of Rio
      Grande do Norte (Brazil) and enhances a small herbarium collection during a
      funding shortage.
AB  - A National Forest Inventory (NFI) encompassing the entire territory of Brazil is
      in progress. It is coordinated and promoted by the Brazilian Forest Service of
      the Ministry of Environment. In each state, the NFI collaborates with local
      herbaria by receiving collected plant material and performing species
      identification. Consultants are hired by the NFI and work at the local herbaria
      under the supervision of a curator. In exchange for curatorial assistance, the
      NFI provides equipment and consumables for the herbarium. Other public projects
      collaborating with NFI are Reflora and the Brazilian Biodiversity Information
      System (SiBBr). Both projects have online platforms that seek to connect herbaria
      and make all their data freely available, including high quality digital images
      of specimens. Through inter-institutional collaboration, the joint interests of
      NFI, Reflora, SiBBr and local herbaria have improved collections, expanded the
      online Reflora database, and provided the NFI with verified species lists. These
      strategic uses of public funding are positively affecting Botany, particularly
      during a period of economic crisis and cuts in research. Here, we illustrate the
      increase in floristic knowledge through the improvement of a herbarium collection
      in Rio Grande do Norte (RN) - the Brazilian state with the lowest levels of plant
      richness. We report 71 new occurrences of vascular plants for RN, belonging
      mainly to the Poaceae, Fabaceae and Malvaceae. Most of the species with new
      occurrences have a Neotropical distribution (21 spp.) and only seven are
      restricted to the Brazilian Northeast. Our findings highlight previous gaps in
      RN's floristic knowledge. The partnership NFI, Reflora, SiBBr and the UFRN
      herbarium improved herbarium curation, digital collection, and quality of data.
      Finally, a fellowship provided by Reflora and SiBBr allowed improving curation by
      distributing duplicates and incorporating the Herbarium of Camara Cascudo Museum.

PMID- 29033669
TI  - Evolutionary algorithms and synthetic biology for directed evolution: commentary
      on "on the mapping of genotype to phenotype in evolutionary algorithms" by Peter
      A. Whigham, Grant Dick, and James Maclaurin.
AB  - I rehearse two issues around the commentary of Whigham and colleagues. (1) There
      really are many more reasons than those given as to why natural evolution cannot
      reasonably find or select the 'optimal' individual. (2) A series of experimental
      molecular biology programmes, known generically as directed evolution, can use
      operators and selection schemes that natural evolution cannot. When developed
      further using the methods of synthetic biology, there are no operators or schemes
      for in silico evolution that cannot be applied precisely to directed evolution.
      The issues raised apply only to natural evolution but not to directed evolution.

PMID- 29033671
TI  - Loss of a Pioneer: Hussein Abdel-Dayem, MD 1934-2017.

PMID- 29033672
TI  - Role of Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography in
      the Evaluation of Head and Neck Carcinoma.
AB  - Fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET
      CT) has been playing a pivotal role in tumor imaging for the past 20 years. Head
      and neck (HN) cancers are a good example that can illustrate such unique role of
      FDG imaging contributing to the patient's management. In this review article, we
      will describe the normal physiological distribution of FDG within HN structures
      focusing on its limitations and pitfalls. In addition, we will be also describing
      its role in the initial staging and restaging of the disease, particularly with
      regard to therapy response assessment. Furthermore, its role in the evaluation of
      patients with malignant cervical adenopathy from an unknown primary will be
      described. In 2016, the Royal College of Radiologists in its third edition
      published evidence-based guidelines for PET-CT use in HN cancer emphasizing its
      rule in all these clinical scenarios that are being described in this review.
      Finally, we will be highlighting future directions in the field of molecular
      imaging of HN tumors with a special emphasis on the new PET tracers.

PMID- 29033673
TI  - Automated Bone Scan Index as Predictors of Survival in Prostate Cancer.
AB  - Prostate cancer (PCa) is the second most diagnosed cancer in men. Early diagnosis
      and right management of PCa is critical to reducing deaths; the life expectancy
      is the main factors to be considered in the management of PCa. Among patients who
      die from PCa, the incidence of skeletal involvement appears to be >85%. Bone scan
      (BS) is the most common method for monitoring bone metastases in patients with
      PCa. The extent of bone metastasis was also associated with patient survival
      until now there is no clinically useful technique for measuring bone tumors and
      includes this information in the risk assessment. An alternative approach is to
      calculate a BS index (BSI) and it has shown clinical significance as a prognostic
      imaging biomarker. Some computer-assisted diagnosis (CAD) systems have been
      developed to measure BSI and are now available. The aim of this study was to
      investigate automated BSI (aBSI) measurements as predictors' survival in PCa.
      Retrospectively cohort studied fifty patients with PCa who had undergone BS
      between January 2010 and December 2011 at our institution. All data collected was
      updated up to August 2016. CAD system analyzing BS images to automatically
      compute BSI measurements. Patients were stratified into three BSI categories BSI
      value 0, BSI value <=1 and BSI value >1. Kaplan-Meier estimates of the survival
      function and the log-rank test were used to indicate a significant difference
      between groups stratified in accordance with the BSI values. A total of 35
      subjects deaths were registered, with a median survival time 36 months after the
      follow-up BS of 5 years. Subjects with low aBSI value had longer overall survival
      in comparison with the other subjects (P = 0.004). aBSI measurements were shown
      to be a strong prognostic survival indicator in PCa; survival is poor in high-BSI
      value.

PMID- 29033670
TI  - Review of lattice results concerning low-energy particle physics: Flavour Lattice
      Averaging Group (FLAG).
AB  - We review lattice results related to pion, kaon, D- and B-meson physics with the
      aim of making them easily accessible to the particle-physics community. More
      specifically, we report on the determination of the light-quark masses, the form
      factor [Formula: see text], arising in the semileptonic [Formula: see text]
      transition at zero momentum transfer, as well as the decay constant ratio
      [Formula: see text] and its consequences for the CKM matrix elements [Formula:
      see text] and [Formula: see text]. Furthermore, we describe the results obtained
      on the lattice for some of the low-energy constants of [Formula: see text] and
      [Formula: see text] Chiral Perturbation Theory. We review the determination of
      the [Formula: see text] parameter of neutral kaon mixing as well as the
      additional four B parameters that arise in theories of physics beyond the
      Standard Model. The latter quantities are an addition compared to the previous
      review. For the heavy-quark sector, we provide results for [Formula: see text]
      and [Formula: see text] (also new compared to the previous review), as well as
      those for D- and B-meson-decay constants, form factors, and mixing parameters.
      These are the heavy-quark quantities most relevant for the determination of CKM
      matrix elements and the global CKM unitarity-triangle fit. Finally, we review the
      status of lattice determinations of the strong coupling constant [Formula: see
      text].

PMID- 29033674
TI  - Appearance of Adrenal Myelolipomas on 2-deoxy-2-(18F) fluoro-D-glucose Positron
      Emission Tomography-Computed Tomography.
AB  - With the widespread use of 2-deoxy-2-(18F) fluoro-D-glucose positron emission
      tomography-computed tomography (FDG PET/CT) in oncologic imaging, it has become
      increasingly important for physicians who interpret FDG PET/CT scans to
      confidently recognize the spectrum of incidentally encountered benign and
      malignant findings. The adrenal glands represent an interesting nexus of multiple
      rare and common benign intrinsic tumors as well as metastases from a variety of
      primary malignancies. Given the breadth of adrenal gland pathology, careful
      description of the FDG PET/CT appearance of these pathologies is of value to help
      reduce misinterpretation. In this manuscript, we retrospectively and
      systematically review the FDG PET/CT imaging characteristics of benign adrenal
      myelolipomas in a small consecutive patient series. The myelolipomas in this
      series demonstrated differing degrees of macroscopic fat visible on CT, with
      generally mild FDG uptake fusing to the nonfatty portions of the lesions. At
      imaging follow-up, all of the myelolipomas in this series remained unchanged in
      appearance, helping to confirm their benign nature. The typical appearance of a
      myelolipoma on FDG PET/CT is a fat-containing adrenal mass with low-level FDG
      uptake in the nonfatty aspects of the mass, and such a lesion requires no further
      imaging workup.

PMID- 29033675
TI  - Considering the Relationship between Quantitative Parameters and Prognostic
      Factors in Breast Cancer: Can Mean Standardized Uptake Value be an Alternative to
      Maximum Standardized Uptake Value?
AB  - It was aimed to investigate the correlation between maximum standardized uptake
      value (SUVmax), mean standardized uptake value (SUVmean), and retention index
      (RI), which represents the quantitative evaluation of the uptake of 18F-fluoro-2
      deoxy-D-glucose (18F-FDG) used in positron emission tomography (PET) and
      clinicopathologic as well as biologic prognostic factors. Forty-one women with
      breast cancer who were histopathologically diagnosed were included in this study.
      Neoadjuvant chemotherapy was applied to all patients before PET/computed
      tomography (CT). After FDG injection, PET/CT screening was applied within the 1st
      h (PET-1) and in the 2nd h (PET-2). SUVmax, SUVmean, SUVmax RI, and SUVmean RI of
      every image were calculated qualitatively and semiquantitatively. The correlation
      between quantitative and semiquantitative PET parameters and biologic as well as
      clinicopathologic prognosis factors was evaluated. Statistically, significant
      positive correlation was found between lymph nodes (LNs), which were evaluated by
      clinical picture, clinical stage as well as histopathologically and quantitative
      PET parameters (SUVmax1, SUVmax2,, RImax, SUVmean1, SUVmean2, RImean) (P < 0.05).
      While statistically significant correlation with RImax was detected only by LN
      (histopathological), correlations with RImean were detected by clinical picture,
      clinical stage, metabolic stage, and LN (histopathological). Statistically,
      significant correlation was found between RImax and estrogen receptor in patients
      who were histopathologically diagnosed with invasive ductal carcinoma (n = 34) (P
      < 0.05). We detected correlations between biologic and clinicopathologic
      prognostic factors and SUVmax as well as SUVmean values in breast carcinoma.
      SUVmean values may provide important knowledge when the correlation between
      prognostic factors and PET parameters is investigated even if they are not used
      routinely.

PMID- 29033676
TI  - The Role of Fluorodeoxy-D-glucose Positron Emission Tomography/Computed
      Tomography in Nodal Staging of Nonsmall Cell Lung Cancer in Sequential Surgical
      Algorithm.
AB  - With nonsmall cell lung cancer (NSCLC), accurate mediastinal nodal staging is
      crucial to determine whether a patient is or is not a surgical candidate.
      Traditionally, computed tomography (CT) and fluorodeoxy-D-glucose (FDG) positron
      emission tomography (PET)/CT are the initial steps followed by tissue sampling
      through mediastinoscopy and/or thoracotomy, which are invasive procedures. There
      is controversy regarding the possibility of omission of the invasive diagnostic
      procedures and solely relying on noninvasive presurgical staging CT and FDG
      PET/CT results. Eighty-three patients who had PET/CT, mediastinoscopy, and
      thoracotomy for NSCLC were analyzed. For all lymph nodes that may be sampled by
      mediastinoscopy, PET/CT sensitivity was 80%, specificity was 86%, positive
      predictive value was 47%, and negative predictive value (NPV) was 97%; and for
      those in this group whose clinical stage was T1/T2 M0, sensitivity was 100% and
      specificity was 84%. For lymph nodes accessible only at thoracotomy, sensitivity
      was 42% and specificity was 88%. FDG PET/CT is accurate in assessing stations
      2R/L, 4R/L, and 7 nodes and has the potential to replace mediastinoscopy in the
      treatment algorithm of T1/T2 M0 disease. A negative PET/CT may potentially
      prevent the patient from invasive mediastinoscopy given its high NPV. However, a
      patient with positive PET/CT should undergo tissue biopsy with pathology
      confirmation.

PMID- 29033677
TI  - Diagnostic Accuracy and Impact of Fluorodeoxyglucose Positron Emission
      Tomography/Computed Tomography in Preoperative Staging of Cutaneous Malignant
      Melanoma: Results of a Prospective Study in Indian Population.
AB  - The aim of the study was to evaluate the diagnostic accuracy of positron emission
      tomography/computed tomography (PET/CT) in staging patients with primary
      cutaneous malignant melanoma (CMM). We further compared the performance of PET/CT
      with conventional imaging (CI) (CT and ultrasonography [USG]) and assessed the
      impact of PET/CT on disease management. This was a single institution,
      prospective, double-blinded study, recruiting a total of 70 treatment naive
      patients. The sensitivity, specificity, negative predictive value (NPV), and
      positive predictive value (PPV) of PET/CT for N staging were 86%, 96%, 80%, and
      97%, respectively. The sensitivity, specificity, NPV, and PPV of PET/CT for M
      staging were 87%, 100%, 93%, and 100%, respectively. The diagnostic accuracy of
      the PET/CT was superior to CI for N staging (90% vs. 84% for CT and 80% for USG)
      and M staging (95% vs. 90% for CT). No statistically significant difference was
      noted between PET/CT and CI for N staging (PET/CT vs. CT, P = 0.125; PET/CT vs.
      USG, P-0.063) or M staging (PET/CT vs. CT, P = 0.125). PET/CT upstaged 23% of
      patients with clinically localized disease and 58% of patients with clinically
      palpable regional nodes. To conclude, fluorodeoxyglucose PET/CT is a highly
      sensitive and specific imaging modality for preoperative staging of primary CMMs.
      PET/CT impacts disease management in significant number of patients and should be
      especially recommended in all patients with clinically palpable regional nodes.

PMID- 29033678
TI  - Quantitative Metabolic Volumetric Product on 18Fluorine-2fluoro-2-deoxy-D-glucose
      positron Emission Tomography/Computed Tomography in Assessing Treatment Response
      to Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis: Multiparametric
      Analysis Integrating American College of Rheumatology/European League Against
      Rheumatism Criteria.
AB  - The purpose of this study was to assess the role of fluoro-2-deoxy-D-glucose
      positron emission tomography/computed tomography (FDG-PET/CT) in the evaluation
      of treatment response evaluation to disease-modifying antirheumatic drug (DMARD)
      therapy in patients of rheumatoid arthritis (RA). A total of ten patients with
      proven diagnosis of RA as per the 2010 American College of Rheumatology/European
      League against Rheumatism (EULAR) criteria were prospectively evaluated. All
      patients underwent clinical and biochemical evaluation and a baseline FDG-PET/CT
      with assessment of maximum standardized uptake value and metabolic volumetric
      product (MVP) values. DMARD therapy was started with a combination of
      hydroxychloroquine and sulfasalazine. On follow-up at 3 and 6 months, the
      response to treatment was assessed by clinical, biochemical, and FDG-PET/CT
      parameters. These parameters were analyzed in a combined manner, and the patients
      were grouped into 4 categories as per response to DMARD therapy - complete
      response, good response, mixed response, and no response. Evaluation of treatment
      response in ten patients at 3rd month and in nine patients at 6 months showed (a)
      agreement for MVP, biochemical parameters with clinical symptomatic assessment in
      all patients, (b) while agreement for EULAR score was noted in only three
      patients and disagreement in seven patients with clinical symptoms Response EULAR
      (rEULAR) (0.37) and at 6 months in only three patients and disagreement in six
      patients, rEULAR (0.52). The correlation factors at 3rd month and 6th months
      were, respectively, as follows: rMVP (0.67 and 0.75), response RA factor (0.54
      and 0.74), response erythrocyte sedimentation rate (0.81 and 0.73), response C
      reactive protein (0.78 and 0.51), and response anti-cyclic citrullinated peptide
      antibodies (0.33 and 0.54). The overall response to DMARD therapy at 3 months was
      assessed with results showing good response by four cases (40%), mixed response
      by 1 (10%), no response by 5 (50%), and complete response by none (0%). Step-up
      therapy at 3 months was initiated in four patients showing
      nonresponse/progression on clinical symptomatic assessment; of these, two
      patients showed a good response, one mixed response, and the remaining one
      continued to show nonresponse at 6 months follow-up. One patient who had a
      minimal response at 3 months on PET-CT (only 5.96% reduction of MVP) was
      continued on the same DMARD in view of clinical symptomatic good response (at 3
      months) but ultimately had disease progression in all scales and worsening of
      symptom (at 6 months). FDG-PET/CT-based assessment of inflammatory activity noted
      in the joints of RA with quantitative parameters can be a promising approach for
      the whole body assessment of RA disease activity and treatment response
      assessment, especially in inconclusive cases and correlates well with other
      parameters. MVP can be used as a useful objective and adjunct parameter for
      assessing response to treatment.

PMID- 29033679
TI  - Incremental Value of Single-photon Emission Computed Tomography-computed
      Tomography for Characterization of Skeletal Lesions in Breast Cancer Patients.
AB  - The incremental value of single-photon emission computed tomography-computed
      tomography (SPECT-CT) over planar bone scintigraphy and SPECT in detecting
      skeletal lesions in breast cancer patients and its effect on patient management
      is assessed in this study. This is a prospective study which was conducted over 1
      year duration. Whole-body planar scintigraphy, SPECT, and SPECT-CT were performed
      in 85 breast cancer patients with total of 128 lesions. Correlative imaging and
      clinical follow-up was used as the reference standard. McNemar's multistep
      analysis was performed for each patient and each lesion. On patient-wise
      analysis, 47 patients had equivocal diagnosis on planar bone scintigraphy, 28 on
      SPECT, and eight on SPECT-CT. On lesion-wise analysis, there were 72 equivocal
      lesions on planar bone scintigraphy, 48 on SPECT, and 15 on SPECT-CT. Overall,
      SPECT-CT resulted in a significant reduction in the proportion of equivocal
      diagnosis on both patient-wise (P < 0.004) and lesion-wise basis (P < 0.004),
      irrespective of the skeletal region involved. The sensitivity on a per-patient
      basis was 43%, 58%, and 78% for planar bone scintigraphy, SPECT, and SPECT-CT,
      respectively. Similarly, the specificity was 85%, 92%, and 94% for planar bone
      scintigraphy, SPECT, and SPECT-CT, respectively. Patient management was correctly
      altered in 32% of the patients based on SPECT-CT interpretation. Our data suggest
      that adding SPECT-CT to whole-body imaging significantly improves sensitivity and
      specificity in diagnosing bone metastases and significantly reduces the
      proportion of equivocal diagnosis in all regions of the skeleton. The most
      important outcome is derived from the accurate alteration in patient management
      clinically by down- and up-staging of patients and a more precise identification
      of metastatic extent.

PMID- 29033680
TI  - The Utility of 99mTechnetium-mercaptoacetyltriglycine Renogram in Assessing the
      Baseline Renal Function of a Rare Incidental Ectopic Thoracic Kidney.
AB  - Ectopic thoracic kidney is an extremely rare condition caused by the abnormal
      location of one or both kidneys in the thoracic cavity. They are usually
      discovered incidentally on routine imaging. Although commonly asymptomatic,
      thoracic kidneys are at a risk of malrotation, pelviureteric junction
      obstruction, and subsequent obstructive nephropathy, by virtue of their long
      pedicle. We present a case report of an incidental thoracic kidney, for which a
      99mtechnetium-mercaptoacetyltriglycine (99mTc-MAG3) renogram was performed to
      assess the baseline renal function. Although few reports are published in the
      literature using 99mTc-MAG3 renogram for this indication, we demonstrate a safe
      and feasible study to establish a baseline assessment of renal function in this
      group of patients.

PMID- 29033681
TI  - Postoperative Intraperitoneal Bladder Rupture Detected by Renal Scintigraphy: The
      Importance of Postvoid Imaging.
AB  - Iatrogenic intraperitoneal bladder rupture is an entity that may present in a
      patient with idiopathic ascites. Nuclear scintigraphy is an unusual modality for
      the diagnosis of this etiology, and in particular, the postvoid imaging
      demonstrates critical findings. We present a case report, pertinent imaging, and
      a review of literature.

PMID- 29033682
TI  - Usefulness of Tc99m-mebrofenin Hepatobiliary Scintigraphy and Single Photon
      Emission Computed Tomography/Computed Tomography in the Diagnosis of
      Bronchobiliary Fistula.
AB  - Bronchobiliary fistula (BBF), a rare complication of liver disease, is an
      abnormal communication between the biliary tract and bronchial tree. BBF may
      occur as a consequence of local liver infections such as hydatid or amebic
      disease, pyogenic liver abscess or trauma to the liver, obstruction of biliary
      tract, and tumor. As such management of liver disease with BBF is very difficult
      and often associated with a high rate of morbidity and mortality. Therefore,
      timely diagnosis of BBF is imperative. Hepatobiliary scintigraphy along with
      hybrid single photon emission computed tomography/computed tomography using Tc99m
      mebrofenin is a very useful noninvasive imaging modality, in the diagnosis of
      BBF.

PMID- 29033683
TI  - Regional Liver Disorder with Differences in the Accumulation of 99mTc-phytate and
      99mTc-galactosyl Human Serum Albumin.
AB  - We report a 56-year-old woman with regional liver disorder due to acute
      hepatitis. Computed tomographic images showed low signal density at a plain phase
      and prolonged contrast effect at a late phase in the left hepatic lobe, in which
      an accumulation of 99mTc-phytate increased, whereas that of 99mTc-galactosyl
      human serum albumin (GSA) decreased. Meanwhile, in the right lobe, an
      accumulation of 99mTc-GSA showed more increased than that of 99mTc-phytate. Liver
      biopsy showed massive hepatocyte necrosis and interface hepatitis in the left
      lobe, and moderate hepatitis in the right lobe. Differences in the accumulation
      between these scintigrams were helpful for understanding rapid necrosis in the
      left lobe, resulting in a compensatory enlargement of the right lobe. Clinicians
      should be aware that some cases of acute hepatitis cause regional liver disorder
      although most cases show homogeneous inflammation.

PMID- 29033684
TI  - Fluorine-18-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography/Computed
      Tomography Masquerading as a Case of Sporadic Malignant Peripheral Nerve Sheath
      Tumor of Lower Extremity Presenting as Massive Lower Limb Edema.
AB  - Malignant peripheral nerve sheath tumors (MPNSTs) are rare neuroectodermal tumors
      resulting from the malignant transformation of benign plexiform neurofibromas.
      The sporadic form of these tumors is rare than familial variants (seen in
      neurofibromatosis Type 1) and making the diagnosis difficult. We are presenting a
      case of 40--year-old female with the complaint of progressive swelling of lower
      limb with initial suspicion of lymphedema and underwent lymphoscintigraphy,
      magnetic resonance imaging, and finally fluorine-18-2-fluoro-2-deoxy-D-glucose
      positron emission tomography/computed tomography scans were done to rule out
      mitotic etiology and extent of the disease. The patient underwent below-knee
      amputation, and histopathological examination confirmed the diagnosis of sporadic
      MPNST.

PMID- 29033685
TI  - Evaluation and Identification of Lumbosacral Transitional Vertebra Causing
      Intractable Low Back Pain Utilizing Bone Single-Photon Emission Tomography with
      Computed Tomography.
AB  - The cause of low back pain due to lumbosacral transitional vertebra (LSTV) still
      remains a debated topic. Functional imaging with bone scintigraphy has been a
      valuable adjunct in its assessment; however, in recent years, the additional
      utility of single-photon emission tomography with computed tomography (SPECT/CT)
      is evolving as the imaging modality of choice in identifying range of complex
      lower back pain sources, leading to the provision of suitable treatment options.
      We present a case demonstrating a variant type of LSTV as a source of pain
      localized and delineated on hybrid SPECT/CT imaging treated by minimally invasive
      microendoscopic resection of the pseudoarticulations.

PMID- 29033686
TI  - Serendipitous Detection of Extraosseous Metastases on Bone Scintigraphy: Utility
      of Cross-sectional and Correlative Imaging.
AB  - Whole body bone scintigraphy is most commonly used imaging modality to detect and
      assess the extent of osteoblastic osseous metastases in malignant conditions,
      though visceral metastases need additional imaging. The authors describe a case
      of 50-year-old postoperative breast cancer female where bone scintigraphy showed
      soft tissue uptake in thorax and hepatic region in addition to multiple skeletal
      metastases, indicating the involvement of three different organs by metastatic
      disease. The present case highlights that extraosseous tracer uptake in addition
      to abnormal osseous tracer uptake may raise the suspicion of widespread and
      visceral metastatic disease and warrant further evaluation in the form of cross
      sectional and correlative imaging.

PMID- 29033687
TI  - Interpretation and Diplomacy Aspects of Authority and Care in Imaging Reports.
AB  - Whereas the creative performance of the physician for nuclear medicine is
      measured against his/her written report, the value of the message will not only
      be judged by the precision of the medical statement. The same result can be
      attributed to different words. Numerous habitual and accidental factors exert
      influence on the decision on what is said and what is not said, how it is
      assessed, and what is ignored. The less certain a diagnosis is, and the less
      favorable its possible consequences are, the more subtleties and paraphrases
      should be expected within the report. The decision on the nature and the volume
      of the written report will not only be taken by the time of recording, but the
      way is prepared by the knowledge of the patient's history and symptoms, the
      personal relationship to him/her as well as by a set of conditions throughout the
      inspection of the images. The intuitiveness accompanying the information transfer
      in imaging diagnostics does not only explain the differences in volume and depth
      of diagnosis and differential diagnosis but also the range of diagnostic and
      therapeutic recommendations.

PMID- 29033688
TI  - 68Ga-Prostate-specific Membrane Antigen Positron Emission Tomography/Computed
      Tomography: How Much Specific It Is?

PMID- 29033689
TI  - Designing local solutions for emptying pit latrines in low-income urban
      settlements (Malawi).
AB  - A lack of effective options in local technology poses challenges when onsite
      household sanitation facilities are eventually filled to capacity in unplanned
      settlement areas within Mzuzu City, located in northern Malawi. Vacuum trucks
      currently dominate the market but focus on emptying septic tanks in the more
      easily accessible planned settlement areas, rather than servicing the pit
      latrines common in unplanned settlement areas. As a result, households in the
      unplanned settlement areas within Mzuzu rely primarily on manual pit emptying
      (i.e., shoveling by hand) or digging a new pit latrine. These practices have
      associated health risks and are limited by space constraints. This research
      focused on filling the technological gap through the design, development, and
      testing of a pedal powered modified Gulper pump using locally available materials
      and fabrication. A modified pedal powered Gulper technology was developed and
      demonstrated to be capable of lifting fecal sludge from a depth of 1.5 m with a
      mean flow rate of 0.00058 m3/s. If the trash content was low, a typical pit
      latrine with a volume of 1-4 m3 could be emptied within 1-2 h. Based on the
      findings in our research Phase IV, the pedal powered Gulper modification is
      promising as a potential emptying technology for lined pit latrines in unplanned
      settlement areas. The success rate of the technology is about 17% (5 out 30
      sampled lined pit latrines were successful) and reflects the difficulty in
      finding a single technology that can work well in all types of pit latrines with
      varying contents. We note that cost should not be the only design criteria and
      acknowledge the challenge of handling trash in pit latrines.

PMID- 29033690
TI  - Dual EGFR and BRAF blockade overcomes resistance to vemurafenib in BRAF mutated
      thyroid carcinoma cells.
AB  - BACKGROUND: BRAF inhibitors are effective anticancer agents in BRAF-mutated
      melanomas. By contrast, evidences about sensitivity of thyroid carcinomas to BRAF
      inhibition are conflicting and it has been proposed that BRAF V600E thyroid
      carcinoma cells are less sensitive to BRAF inhibitors due to activation of
      parallel signaling pathways. This study evaluated the hypothesis that feedback
      activation of EGFR signaling counteracts the cytostatic activity of vemurafenib
      (PLX4032) in BRAF V600E thyroid carcinoma cells. METHODS: Cell proliferation,
      cell cycle distribution, induction of apoptosis and EGFR and AKT signaling were
      evaluated in thyroid carcinoma cell lines bearing the BRAF V600E mutation in
      response to PLX4032. RESULTS: A partial and transient cytostatic response to
      PLX4032 was observed in thyroid carcinoma cell lines bearing the BRAF V600E
      mutation, with lack of full inhibition of ERK pathway. Interestingly, the
      exposure of thyroid carcinoma cells to PLX4032 resulted in a rapid feedback
      activation of EGFR signaling with parallel activation of AKT phosphorylation.
      Consistently, the dual inhibition of EGFR and BRAF, through combination therapy
      with PLX4032 and gefitinib, resulted in prevention of EGFR phosphorylation and
      sustained inhibition of ERK and AKT signaling and cell proliferation. Of note,
      the combined treatment with gefitinib and vemurafenib or the exposure of EGFR
      silenced thyroid carcinoma cells to vemurafenib induced synthetic lethality
      compared to single agents. CONCLUSIONS: These data suggest that the dual EGFR and
      BRAF blockade represents a strategy to by-pass resistance to BRAF inhibitors in
      thyroid carcinoma cells.

PMID- 29033692
TI  - SEQUENCE SEGMENTATION USING JOINT RNN AND STRUCTURED PREDICTION MODELS.
AB  - We describe and analyze a simple and effective algorithm for sequence
      segmentation applied to speech processing tasks. We propose a neural architecture
      that is composed of two modules trained jointly: a recurrent neural network (RNN)
      module and a structured prediction model. The RNN outputs are considered as
      feature functions to the structured model. The overall model is trained with a
      structured loss function which can be designed to the given segmentation task. We
      demonstrate the effectiveness of our method by applying it to two simple tasks
      commonly used in phonetic studies: word segmentation and voice onset time
      segmentation. Results suggest the proposed model is superior to previous methods,
      obtaining state-of-the-art results on the tested datasets.

PMID- 29033691
TI  - Identification of genes and pathways potentially related to PHF20 by gene
      expression profile analysis of glioblastoma U87 cell line.
AB  - BACKGROUND: Glioblastoma is the most common and aggressive brain tumor associated
      with a poor prognosis. Plant homeodomain finger protein 20 (PHF20) is highly
      expressed in primary human gliomas and its expression is associated with tumor
      grade. However, the molecular mechanism by which PHF20 regulates glioblastoma
      remains poorly understood. METHODS: Genome wide gene expression analysis was
      performed to identify differentially expressed genes (DEGs) in U87 cells with
      PHF20 gene knockdown. Gene ontology (GO) and pathway enrichment analyses were
      performed to investigate the functions and pathways of DEGs. Pathway-net and
      signal-net analyses were conducted to identify the key genes and pathways related
      to PHF20. RESULTS: Expression of 540 genes, including FEN1 and CCL3, were
      significantly altered upon PHF20 gene silencing. GO analysis results showed that
      DEGs were significantly enriched in small molecule metabolic and apoptotic
      processes. Pathway analysis indicated that DEGs were mainly involved in cancer
      and metabolic pathways. The MAPK, apoptosis and p53 signaling pathways were
      identified as the hub pathways in the pathway network, while PLCB1, NRAS and PIK3
      s were hub genes in the signaling network. CONCLUSIONS: Our findings indicated
      that PHF20 is a pivotal upstream regulator. It affects the occurrence and
      development of glioma by regulating a series of tumor-related genes, such as
      FEN1, CCL3, PLCB1, NRAS and PIK3s, and activation of apoptosis signaling
      pathways. Therefore, PHF20 might be a novel biomarker for early diagnosis, and a
      potential target for glioblastoma therapies.

PMID- 29033693
TI  - A Case for Data Commons: Toward Data Science as a Service.
AB  - Data commons collocate data, storage, and computing infrastructure with core
      services and commonly used tools and applications for managing, analyzing, and
      sharing data to create an interoperable resource for the research community. An
      architecture for data commons is described, as well as some lessons learned from
      operating several large-scale data commons.

PMID- 29033694
TI  - Reading Development in Typically Developing Children and Children With Prenatal
      or Perinatal Brain Lesions: Differential School Year and Summer Growth.
AB  - Summer slide, uneven growth of academic skills over the calendar year, captures
      the fact that the learning gains children make over the school year do not
      continue at the same pace over the summer, when children are typically not in
      school. We compared growth of reading skills during the school year and over the
      summer months in children with pre-or perinatal brain lesion (PL) and typically
      developing (TD) children from varying socioeconomic status (SES) backgrounds as a
      new way to probe the role of structured environmental support in functional
      plasticity for reading skills in children with PL. Results showed that children
      with PL performed lower than TD children on both reading decoding and reading
      comprehension. Group differences were primarily driven by children with larger
      lesions and children with right hemisphere lesions (RH). For reading
      comprehension, children with RH showed greater growth during the school year but
      more slide during the summer months than both TD children and children with left
      hemisphere lesions, implicating a particularly strong role of structured input in
      supporting reading comprehension in this group. TD children from lower SES
      backgrounds fell behind their TD peers from higher SES backgrounds on decoding
      and reading comprehension, but did not show differential patterns of school year
      and summer growth. Overall, results highlight the importance of considering the
      role of a host of factors interacting at multiple levels of analyses, including
      biological and environmental, in influencing developmental trajectories of
      typically and atypically-developing children.

PMID- 29033695
TI  - Sexual health knowledge and stigma in a community sample of HIV-positive gay,
      bisexual and other men who have sex with men in Puerto Rico.
AB  - Gay, bisexual and other men who have sex with men (GBMSM) are at increased risk
      for HIV infection and disease progression. Also, HIV-positive GBMSM are among
      those less likely to be retained in care. In this study we analyzed sexual health
      knowledge (SHK) and various manifestations of stigma in a community sample of HIV
      positive GBMSM in Puerto Rico. The sample reports overall low SHK scores, and
      lower score were associated with low educational attainment, unemployment, low
      income, and with self-identifying heterosexual participants. Almost half of the
      sample reported moderate to severe perceived gay stigma, 68.4% reported moderate
      to severe hidden-gay stigma, and 30.6% reported moderate to severe HIV-felt
      stigma. Further research is recommended to obtain culturally congruent
      information and develop interventions addressing the multiple layers of stigma in
      the social context where the interventions will be delivered.

PMID- 29033696
TI  - Spatial Disparity of HIV/AIDS Service Providers: The Case of Miami-Dade County.
AB  - This paper examines the spatial disparity between the HIV/AIDS service providers
      and the HIV/AIDS patients. The empirical focus is on Miami-Dade, a large
      metropolitan county in the United States with a Latino population majority and a
      high AIDS incidence rate. This exploratory study contributes to the existing
      literature on geographical access to health providers. Geographic Information
      System (GIS) is used to examine the spatial disparity between the service
      providers and the patients. The study reveals that aggregate-level analysis masks
      the reality of the spatial disparity. Miami Dade County's Health Department
      focuses on aggregate zones for prioritizing its resources. At this level, there
      is little spatial disparity. However, evidence of spatial disparity emerges at
      the ZIP-code-level analysis. The major lesson from the study is that health
      policies need to be based on a finer-grained analysis to address spatial
      disparity.

PMID- 29033697
TI  - Santeria as Informal Mental Health Support Among U.S. Latinos with Cancer.
AB  - This article explores and examines Santeria's function as a culturally congruent
      informal mental health support that assists U.S. Latinos to cope with the
      psychosocial sequelae of living with cancer. Research has demonstrated that
      Santeria serves as a mediating institution for many Latinos. The tradition
      functions as both a religion and a health care system within various Latino
      subgroups and has functioned as an informal mental health service in occurrences
      of health versus illness.

PMID- 29033698
TI  - Older Adult Video Game Preferences in Practice: Investigating the Effects of
      Competing or Cooperating.
AB  - Video game interventions with the aim to improve cognition have shown promise for
      both younger (e.g., Powers et al., 2013) and older adults (e.g., Toril, Reales,
      and Ballesteros, 2014). Most studies suggest that fast-paced action games produce
      the largest benefits, but a recent video game intervention with older adults
      found that an action game intervention can result in poor adherence (Boot et al.,
      2013). To increase intervention adherence, we investigated older adult video game
      preferences that might bolster adherence by having participants play a
      competitive game (Mario Kart DS) or a cooperative game (Lego Star Wars: The
      Complete Saga) alone or with a partner. Although hypotheses regarding cooperative
      and multi-player gameplay were not supported, converging evidence suggests multi
      player game play may lead to greater enjoyment, which was related to intervention
      adherence in a previous study (Boot et al., 2013). Insights for gaming
      intervention studies in older populations are also provided.

PMID- 29033699
TI  - Gaming Preferences of Aging Generations.
AB  - Increasing evidence suggests that action digital game training can improve a
      variety of perceptual and cognitive abilities, including those that decline most
      with age. Unfortunately, previous work has found that older adults dislike these
      games and adherence may be poor for action game-based interventions. The focus of
      the current study was to better understand the types of games older adults are
      willing to play and explore predictors of game preference (e.g., gender, age,
      technology experience, personality). With this information action games might be
      modified or developed to maximize adherence and cognitive benefit. Older adults
      were administered a modified version of an existing game questionnaire and a
      custom game preference survey. Clear preferences were observed that were similar
      between participants with and without previous digital game experience (with
      puzzle and intellectually stimulating games being most interesting to older
      adults in our sample, and massively multiplayer online games and first-person
      shooters being least interesting). Personality, demographic, and technology
      experience variables were also collected. Interesting trends suggested the
      possibility that several demographic and personality variables might be
      predictive of game preference. Results have implications for future directions of
      research, designing games that would appeal to older adult audiences, and for how
      to design custom games to maximize intervention adherence based on individual
      difference characteristics.

PMID- 29033700
TI  - Supportive home health care technology for older adults: Attitudes and
      implementation.
AB  - Healthcare delivered at home via telehealth technology may save on both
      individual and societal healthcare costs. Three studies investigated potential
      attitudinal barriers to home healthcare adoption. Results from the first
      concerning adults' privacy concerns and mobile device preferences showed that
      attitudes clustered into 4 factors and that older adults, particularly males,
      showed less concern than younger adults about privacy. The second and third
      studies explored comfort with a wearable device and the role of aesthetics over 2
      week and 6-month intervals. Results showed that older adults had stable ratings
      for comfort while wearing a watch device designed to collect data in real time
      and that aspects of physical comfort predicted use over a six-month time period.
      Taken together, the studies provide evidence that attitudes about privacy and
      comfort for wearable health devices are unlikely to be significant barriers to
      adoption, though first impressions are important for all age groups.

PMID- 29033702
TI  - Recycling greenhouse gas fossil fuel emissions into low radiocarbon food products
      to reduce human genetic damage.
AB  - Radiocarbon from nuclear fallout is a known health risk. However, corresponding
      risks from natural background radiocarbon incorporated directly into human
      genetic material have not been fully appreciated. Here we show that the average
      person will experience between 3.4 * 1010 and 3.4 * 1011 lifetime chromosomal
      damage events from natural background radiocarbon incorporated into DNA and
      histones, potentially leading to cancer, birth defects, or accelerated aging.
      This human genetic damage can be significantly reduced using low radiocarbon
      foods produced by growing plants in CO2 recycled from ordinary industrial
      greenhouse gas fossil fuel emissions, providing additional incentive for the
      carbon sequestration.

PMID- 29033704
TI  - Sedative and hypnotic effects of Iranian traditional medicinal herbs used for
      treatment of insomnia.
AB  - For tens of centuries, plants have been highly valued and regularly used as
      medicine amongst the masses. Insomnia, a loss of sleep, is mostly treated by
      synthetic sleeping tablets these days. However, questions have been raised about
      the safety of prolonged use of artificial sedatives due to their deleterious side
      effects such as physical dependence. In recent years, there has been an
      increasing propensity to preclude insomnia by herbal medicines throughout the
      world. Many herbs have a lengthy background in terms of insomnia treatment in
      Iran. This paper gives an account of previously published research on sedative
      and hypnotic effects of medicinal herbs used for treatment of insomnia in Iranian
      traditional medicine.

PMID- 29033705
TI  - Two cases of bronchiolitis obliterans organizing pneumonia syndrome after
      postoperative irradiation for breast cancer.
AB  - We report two cases of bronchiolitis obliterans organizing pneumonia (BOOP)
      syndrome that developed after postoperative radiation therapy for breast cancer.
      In both patients, chest radiographs and computed tomography (CT) showed multiple
      consolidations outside the irradiation fields after several months of tangential
      radiation therapy. These patients were diagnosed as having radiation-associated
      BOOP syndrome, based on their clinical course and the findings on examination.
      After treatment with a systemic corticosteroid, radiographic consolidations and
      symptoms improved rapidly. In cases where consolidations appear outside the
      irradiated field, it is important to consider BOOP syndrome as a pulmonary
      complication of radiation therapy for breast cancer.

PMID- 29033701
TI  - Monitoring of environmental exposure to polycyclic aromatic hydrocarbons: a
      review.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a large group of organic compounds
      with two or more fused aromatic rings. They have a relatively low solubility in
      water, but are highly lipophilic. Most of the PAHs with low vapour pressure in
      the air are adsorbed on particles. When dissolved in water or adsorbed on
      particulate matter, PAHs can undergo photodecomposition when exposed to
      ultraviolet light from solar radiation. In the atmosphere, PAHs can react with
      pollutants such as ozone, nitrogen oxides and sulfur dioxide, yielding diones,
      nitro- and dinitro-PAHs, and sulfonic acids, respectively. PAHs may also be
      degraded by some microorganisms in the soil. PAHs are widespread environmental
      contaminants resulting from incomplete combustion of organic materials. The
      occurrence is largely a result of anthropogenic emissions such as fossil fuel
      burning, motor vehicle, waste incinerator, oil refining, coke and asphalt
      production, and aluminum production, etc. PAHs have received increased attention
      in recent years in air pollution studies because some of these compounds are
      highly carcinogenic or mutagenic. Eight PAHs (Car-PAHs) typically considered as
      possible carcinogens are: benzo(a)anthracene, chrysene, benzo(b)fluoranthene,
      benzo(k)fluoranthene, benzo(a)pyrene (B(a)P), dibenzo(a,h)anthracene,
      indeno(1,2,3-cd)pyrene and benzo(g,h,i)perylene. In particular, benzo(a)pyrene
      has been identified as being highly carcinogenic. The US Environmental Protection
      Agency (EPA) has promulgated 16 unsubstituted PAHs (EPA-PAH) as priority
      pollutants. Thus, exposure assessments of PAHs in the developing world are
      important. The scope of this review will be to give an overview of PAH
      concentrations in various environmental samples and to discuss the advantages and
      limitations of applying these parameters in the assessment of environmental risks
      in ecosystems and human health. As it well known, there is an increasing trend to
      use the behavior of pollutants (i.e. bioaccumulation) as well as pollution
      induced biological and biochemical effects on human organisms to evaluate or
      predict the impact of chemicals on ecosystems. Emphasis in this review will,
      therefore, be placed on the use of bioaccumulation and biomarker responses in
      air, soil, water and food, as monitoring tools for the assessment of the risks
      and hazards of PAH concentrations for the ecosystem, as well as on its
      limitations.

PMID- 29033706
TI  - Antibacterial activity of different parts of Peganum harmala L. growing in Iran
      against multi-drug resistant bacteria.
AB  - Peganum harmala L. (Zygophyllaceae) is one of the most famous medicinal plants
      used in traditional medicine of Iran. The aim of this study was to consider
      antibacterial effects of the methanolic extract of different parts of P. harmala
      including root, stem, leaf, flower and seed against some important human
      pathogenic bacteria. Antibacterial properties of methanolic extract of mentioned
      parts were assessed by disc diffusion method. Active extract was fractioned using
      Thin Layer Chromatography; also their synergism activity in combination with
      synthetic antibiotic was evaluated. Among the evaluated parts of P. harmala, the
      root and seed extracts presented antibacterial activity against all of tested
      bacteria even at the lowest concentration. Antibacterial effect of leaf part was
      moderate while stem and flower extracts showed relatively poor activity.
      Antibacterial activity of root extract against most of the tested Gram positive
      bacteria was better than seed extract. Tested against Gram negative bacteria the
      obtained results were inconsistent. MIC (Minimal Inhibitory Concentration) and
      MBC (Minimal Bactericidal Concentration) values for both extracts against MRSA
      (Methicillin Resistant Staphylococcus aureus) and for seed extract against E.
      coli and S. typhi were equal (0.625 mg/ml). TLC (Thin Layer Chromatography)
      results revealed that seed and root extracts were different in terms of nature
      and content of their constituents. Furthermore, these two extracts showed an
      excellent stability to temperature and pH treatment. Also, the seed and root
      extracts showed synergism in combination with novobiocin, colistin and
      carbenicillin. In conclusion, P. harmala can be assigned as a source of
      antibacterial compounds for treatment of infections caused by multi-drug
      resistant (MDR) bacterial pathogens.

PMID- 29033703
TI  - Dark nights behind the white clouds - risks of tobacco smoking on human health
      besides the oral health and malignancy.
AB  - Tobacco smoking is the common practice in a large percentage of the population
      worldwide, and the incidence is continuously increasing. Tobacco smoking is the
      most preventable cause of lung cancer, and it also impairs oral health. People
      are aware of the carcinogenic effects of tobacco smoking on the lungs and oral
      cavity, but it is also a risk factor for many other harmful diseases. This review
      article covers most of the diseases that are associated with tobacco smoking,
      such as coronary artery disease (CAD), diabetes, chronic obstructive pulmonary
      disease (COPD), arthritis, impotency, infertility, tuberculosis, and Alzheimer's
      disease. The association of these diseases with tobacco smoking is discussed in
      detail in this review, along with their possible pathophysiology. This article
      focuses on the ongoing research of these diseases, and aims to raise awareness of
      the hazards of tobacco smoking, and to promote anti-smoking awareness programs.

PMID- 29033707
TI  - Chemical composition and antioxidant potentials of Kigelia pinnata root oil and
      extracts.
AB  - The chemical composition of Kigelia pinnata root oil extracted with n-hexane was
      analyzed by GC/GCMS. The antioxidant potential of the oil was compared to that of
      ethyl acetate and methanol extracts of the root. UV and IR spectroscopic
      techniques were used to carry out partial characterization of the oil and
      extracts. The free radical scavenging activity by spectrophotometric assay on the
      reduction of 1,1-diphenyl-2-picrylhydrazyl (DPPH) was examined while the total
      antioxidant activity (TAA) and relative antioxidant activity (RAA) were compared
      with standard antioxidant, alpha-tocopherol. The antioxidant activity (which
      correlated with the total phenolic content of the extracts) was assumed to be
      from the total phenolic content of the extracts. TAA was found to be higher in
      methanol extract (at 0.25 mg/mL). We hereby report for the first time the major
      component of the oil from the root of Kigelia pinnata to be elaidic acid (56.12
      %). It is a reported toxicant which thereby underscores the risk in the use of
      the plant in traditional therapies.

PMID- 29033708
TI  - Essential oil composition and antimicrobial activity of Lobelia pyramidalis Wall.
AB  - The essential oil of Lobelia pyramidalis was analyzed by GC and GC-MS. A total of
      21 constituents comprising 77.88 % of the total oil were identified. Perilla
      ketone constituted 25.61 % of the oil followed by camphorquinone (12.16 %),
      dibutyl phthalate (10.66 %) and allyl nonanoate (8.47 %). The antimicrobial
      activity of the oil was evaluated using the disc diffusion method and the
      microdilution technique. The results showed that the oil exhibited moderate
      antimicrobial activity.

PMID- 29033709
TI  - Hepatoprotective effect of an aqueous extract of the leaves of Acalypha
      wilkesiana 'Godseffiana' Muell Arg (Euphorbiaceae) against carbon tetrachloride
      induced liver injury in rats.
AB  - The potential of aqueous extract of the leaves of Acalypha wilkesiana, to protect
      against carbon tetrachloride induced liver damage was investigated in Wistar
      albino rats. The carbon tetrachloride was prepared 1:5 (v:v) in olive oil, and
      administered subcutaneously at 1 mL/kg body weight. The extract was administered
      to both normal and carbon tetrachloride treated rats at 100, 200 and 300 mg/kg.
      On fractionation and gas chromatographic analysis of the crude aqueous extract,
      thirty nine known alkaloids were detected, consisting mainly of akuamidine
      (69.027 %), voacangine (26.226 %), echitamine (1.974 %), echitamidine (0.599 %),
      lupanine (0.521 %) and augustamine (0.278 %). Compared to test control, the
      treatment dose dependently produced significantly lower (P<0.05) alkaline
      phosphatase, aspartate and alanine transaminase activities. Histopathological
      studies on the liver sections showed that pre-treatment with the extract
      protected against carbon tetrachloride induced fatty degeneration of hepatocytes,
      thus, confirming the results of the biochemical studies. The above results imply
      that treatment with the plant extract protects the liver against carbon
      tetrachloride induced hepatotoxicity, therefore, justifying the use of Acalypha
      wilkesiana in African traditional health care for the management of liver
      problems.

PMID- 29033711
TI  - Linear chain aldehydes evoke calcium responses in B16 melanoma cells.
AB  - Oxidative stress is involved in various physiological impairing stages, such as
      aging, diabetes, atherosclerosis, cirrhosis, and neurological disorders. Recent
      research indicates that aldehyde compounds derived from oxidized lipids increase
      in cancer patients compared to healthy individuals. Among of them, hexanal, a six
      carbon liner chain aldehyde, is commonly found in cancer patients. Lipid
      oxidation products including aldehydes are in general chemically unstable and
      react with biological molecules such as proteins. The purpose of this study is to
      investigate effects of lipid-derived aldehydes and the related compounds on
      intracellular Ca2+ responses in B16 melanoma cells. Hexanal-induced [Ca2+]i
      elevation is observed in B16 cells in a dose dependent manner, but [Ca2+]i
      changes were observed neither in 3T3-L1 cells nor Caco-2 cells. Propanal, a chain
      length analogue of hexanal, elicited no change in [Ca2+]i, but nonanal initiated
      [Ca2+]i increases. Analogue compounds of hexanal failed to induce [Ca2+]i
      elevation. Furthermore, unsaturated aldehydes known as TRPA1 channel agonists
      also failed to alter [Ca2+]i levels in B16 melanoma cells. Pharmacological
      spectra using inhibitors against intracellular Ca2+ signaling suggest that
      hexanal-induced [Ca2+]i responses in B16 cells might be involved in TRP channels
      other than TRPA1. Our results suggest that saturated aliphatic chain aldehydes
      would be novel compounds for initiating [Ca2+]i increases through very strict
      recognitions of chain saturation, aldehydic base structures, and chain lengths in
      B16 melanoma cells. B16 cells would have sensing mechanisms for oxidative status
      and/or metabolic activities in their growth environment.

PMID- 29033710
TI  - The effect of different antidepressant drugs on oxidative stress after
      lipopolysaccharide administration in mice.
AB  - This study investigated the effect of the serotonin selective reuptake inhibitors
      (SSRIs) fluoxetine, sertraline, fluvoxamine and the tricyclic antidepressant
      (TCA) impiramine on oxidative stress in brain and liver induced by
      lipopolysaccharide administration in mice. Each drug was administered
      subcutaneously at doses of 10 or 20 mg/kg, for two days prior to intraperitoneal
      (i.p.) administration of lipopolysaccharide E (LPS: 200 ug/kg). Mice were
      euthanized 4 h after administration of the lipopolysaccharide. Lipid peroxidation
      (malondialdehyde; MDA), reduced glutathione (GSH) and nitric oxide
      (nitrite/nitrate) concentrations were measured in brain and liver. Results: The
      administration of lipopolysaccharide increased oxidative stress in brain and
      liver; it increased brain MDA by 36.1 and liver MDA by 159.8 %. GSH decreased by
      34.1 % and 64.8 % and nitric oxide increased by 78.7 % and 103.8 % in brain and
      liver, respectively. In brain, MDA decreased after the administration of
      sertraline and by the lower dose of fluoxetine or fluvoxamine, but increased
      after the higher dose of imipramine. Reduced glutathione increased after
      sertraline, fluvoxamine and the lower dose of fluoxetine or imipramine. Nitric
      oxide decreased by sertraline, fluoxetine, fluvoxamine and by the lower dose of
      imipramine. In the liver, all drugs decreased MDA and increased GSH level. Nitric
      oxide is decreased by sertraline, fluvoxamine and by the lower dose of fluoxetine
      or imipramine. It is concluded that, during mild systemic inflammatory illness
      induced by peripheral bacterial endotoxin injection, the SSRIs fluoxetine,
      sertraline and fluvoxamine reduced, while the TCA impiramine increased oxidative
      stress induced in the brain. The SSRIs as well as imipramine reduced oxidative
      stress due to lipopolysaccharide in liver tissue.

PMID- 29033712
TI  - Protective effect of aqueous extract of the rhizomes of Sansevieria liberica
      Gerome and Labroy on carbon tetrachloride induced hepatotoxicity in rats.
AB  - The ability of an aqueous extract of the rhizomes of Sansevieria liberica to
      protect against carbon tetrachloride induced liver injury was investigated in
      Wistar albino rats. The carbon tetrachloride was prepared 1:5 (v:v) in olive oil,
      and administered subcutaneously at 1 mL/kg body weight. The extract was
      administered to both normal and carbon tetrachloride treated rats at 100, 200 and
      300 mg/kg. On gas chromatographic analysis of the extract, twenty nine known
      flavonoids were detected, consisting mainly of 31.94 % apigenin, 20.66 %
      quercetin, 11.28 % kaempferol, 5.99 % naringenin, 5.83 % (-)-epicatechin, 3.69 %
      biochanin, 3.58 % (+)-catechin, 2.72 % diadzein, 2.20 % ellagic acid, 2.04 %
      butein. Compared to test control, the treatment dose dependently produced
      significantly (P<0.05) lower alkaline phosphatase, aspartate transaminase and
      alanine transaminase activities. The plasma total bilirubin and total protein
      levels of the test animals were lower though not significantly. The hepatic
      histopathological studies showed that carbon tetrachloride caused fatty
      degeneration of hepatocytes, which was inhibited by pre-treatment with the
      extract; thus, confirming the results of the biochemical studies. The results of
      this study indicated that treatment with the plant extracts protects the liver
      against carbon tetrachloride induced hepatotoxicity. This supports the use of
      Sansevieria liberica in traditional health care for managing liver problems.

PMID- 29033713
TI  - The role of liver in leptin metabolism in experimental nephrotic syndrome.
AB  - Leptin is a hormone influencing food intake, energy expenditure and body weight.
      It is produced by adipocytes, exerts its effects on brain, endocrine pancreas and
      other organs by activating trans-membrane receptors and is cleared from plasma
      mainly by the kidneys. Several studies have suggested that leptin's effects on
      metabolism are mediated by the liver. Our aim was to evaluate the role of the
      liver in the metabolism of leptin by comparing the serum leptin level in the
      portal vein with that in inferior vena cava and to study the relationship between
      leptin and lipoprotein levels in healthy and nephrotic rats. Experimental
      nephrotic syndrome was conducted in rats by intraperitoneal injection of the
      supernatant from the kidney suspension obtained by previous unilateral
      nephrectomy of the same rat and complete Freund's adjuvant. There was a highly
      significant rise in leptin and lipid profile levels in the nephrotic rats
      compared with the normal rats. A highly significant increase in leptin in the
      inferior vena cava was detected compared with the level in the portal veins of
      nephrotic rats, while insignificant difference was observed in normal rats. This
      work has stressed the role of liver in leptin and lipid metabolism in nephrotic
      rats.

PMID- 29033714
TI  - Design of Strain-Limiting Substrate Materials for Stretchable and Flexible
      Electronics.
AB  - Recently developed classes of electronics for biomedical applications exploit
      substrates that offer low elastic modulus and high stretchability, to allow
      intimate, mechanically biocompatible integration with soft biological tissues. A
      challenge is that such substrates do not generally offer protection of the
      electronics from high peak strains that can occur upon large-scale deformation,
      thereby creating a potential for device failure. The results presented here
      establish a simple route to compliant substrates with strain-limiting mechanics
      based on approaches that complement those of recently described alternatives.
      Here, a thin film or mesh of a high modulus material transferred onto a
      prestrained compliant substrate transforms into wrinkled geometry upon release of
      the prestrain. The structure formed by this process offers a low elastic modulus
      at small strain due to the small effective stiffness of the wrinkled film or
      mesh; it has a high tangent modulus (e.g., >1000 times the elastic modulus) at
      large strain, as the wrinkles disappear and the film/mesh returns to a flat
      geometry. This bilinear stress-strain behavior has an extremely sharp transition
      point, defined by the magnitude of the prestrain. A theoretical model yields
      analytical expressions for the elastic and tangent moduli and the transition
      strain of the bilinear stress-strain relation, with quantitative correspondence
      to finite element analysis and experiments.

PMID- 29033715
TI  - Has goal directed fluid therapy and glycocalyx a role in enhanced recovery after
      anesthesia?

PMID- 29033716
TI  - Transdermal fentanyl as an adjuvant to paravertebral block for pain control after
      breast cancer surgery: A randomized, double-blind controlled trial.
AB  - OBJECTIVE: The aim of this study is to investigate the effect of transdermal
      fentanyl (TDF) as an adjuvant to paravertebral block (PVB) for pain control after
      breast cancer surgery. PATIENTS AND METHODS: This randomized, double-blind trial
      included fifty females with breast cancer scheduled for surgery. They were
      randomly allocated into one of two equal groups. The TDF group used transdermal
      fentanyl patches (TFPs) 25 MUg/h applied 10 h preoperative then PVB with 20 mL of
      bupivacaine 0.25% was done before induction of general anesthesia. The PVB group
      used placebo patches in addition to PVB the same way as TDF group. Postoperative
      pain was assessed with a visual analog scale (VAS) score up to 48 h. Intravenous
      morphine 0.1 mg/kg was given when the VAS is >= 3 or on patient request. The
      primary outcome measures were the time to first request for analgesia and the
      total analgesic consumption in the first 48 h. RESULTS: Relative to the VAS score
      reading was 30 min. After the end of surgery, VAS score decreased significantly
      in the two groups up to 48 postoperative hours and was significantly lower in TDF
      group up to 24 h. The time to first request of additional analgesia was
      significantly longer, and total dose of morphine consumption was significantly
      lower in TDF group (P < 0.001, and P = 0.039, respectively). CONCLUSION: TFPs
      releasing 25 MUg/h is a safe and effective adjuvant to PVB after breast cancer
      surgery. It provides adequate analgesia with reduction of opioid consumption and
      minimal adverse effects.

PMID- 29033717
TI  - Comparison of oropharyngeal leak pressure of air-QTM, i-gelTM, and laryngeal mask
      airway supremeTM in adult patients during general anesthesia: A randomized
      controlled trial.
AB  - STUDY OBJECTIVE: Various randomized controlled trials and a meta-analysis have
      compared i-gelTM and laryngeal mask airway SupremeTM (LMA-STM) in adult patients
      and found that both the devices provided equivalent oropharyngeal leak pressure
      (OLP). However, no randomized controlled trial has compared air-QTM with i-gelTM
      and LMA-STM in adult patient. Hence, we designed this study to compare air-QTM
      with LMA-STM and i-gelTM in adult patients. MATERIALS AND METHODS: A total of 75
      adult patients of the American Society of Anesthesiologists physical status I/II
      of both sexes, between 18 and 60 years, were included in this prospective
      randomized controlled trial conducted in a tertiary care center. Randomization of
      patients was done in three equal groups according to the insertion of
      supraglottic airway device by a computer-generated random number sequence: group
      air-QTM (n = 25), group i-gelTM (n = 25), and group LMA-STM (n = 25). Primary
      outcome of this study was OLP. We also recorded time for successful placement of
      device, ease of device insertion, number of attempts to insert device, and ease
      of gastric tube insertion along with postoperative complications. RESULTS: The
      mean +/- standard deviation OLP of air-QTM, i-gelTM, and LMA-STM was 26.13 +/-
      4.957 cm, 23.75 +/- 5.439 cm, and 24.80 +/- 4.78 cm H2O (P = 0.279). The first
      insertion success rate for air-QTM, i-gelTM, and LMA-STM was 80%, 76%, and 92%,
      respectively (P = 0.353). The insertion time of air-QTM, i-gelTM, and LMA-STM was
      20.6 +/- 4.4, 14.8 +/- 5.4, and 15.2 +/- 4.7 s, respectively (P = 0.000). Time
      taken for air-QTM insertion was significantly higher than time taken for i-gelTM
      (mean difference 5.8 s, P < 0.0001) and LMA-STM (mean difference 5.4 s, P =
      0.0001) insertion. Postoperative complications were similar with all three
      devices. CONCLUSIONS: We concluded that air-QTM, i-gelTM, and LMA-STM were
      equally efficacious in terms of routine airway management in adult patients with
      normal airway anatomy.

PMID- 29033718
TI  - A randomized comparative study assessing efficacy of pain versus comfort scores.
AB  - CONTEXT: Use of language with negative emotional content is likely to increase
      patient's pain and anxiety. AIMS: We designed a single-blinded randomized study
      to compare pain scores with comfort scores and to determine whether the technique
      of pain assessment affects patient's perceptions and experience. SUBJECTS AND
      METHODS: After cesarean section, 180 women were randomized before postanaesthesia
      interview into two groups. Group P women were asked to rate their pain on a 0-10
      point verbal numerical rating scale (VNRS) for pain while Group C women were
      asked to rate their comfort on a 0-10-point VNRS for comfort. All women were
      asked whether the surgical wound was associated with injury or healing. The
      primary outcomes were to compare the incidence of reported pain and to assess
      pain severity as measured by a 0-10-point VNRS for pain compared with an
      equivalent inverted VNRS for comfort. The secondary outcomes were whether the
      wound was associated with injury or healing. STATISTICAL ANALYSIS USED: Data were
      analyzed using Student's t-test and nonparametric Mann-Whitney U-test, performed
      at a significance level of alpha =0.05. RESULTS: In Group P, 62 women (68.9%)
      reported pain compared with only 49 women (54.4%) in Group C (P < 0.05). There
      were no significant differences between groups for VNRS at rest and on movement.
      In Group P, thirty women (33.33%) reported sensations as injury compared with
      only 11 women (12.22%) in Group C (P < 0.001). CONCLUSIONS: Assessment of pain
      using positive word like comfort decreases its incidence with no effect on its
      severity when measured by comfort score and also affects patient's postsurgical
      perceptions.

PMID- 29033719
TI  - Epidemiology and characteristics of nosocomial infections in critically ill
      patients in a tertiary care Intensive Care Unit of Northern India.
AB  - BACKGROUND AND AIMS: The prevalence of nosocomial infection is higher in the
      Intensive Care Unit (ICU) than other areas of the hospital. The present
      observational study was undertaken to describe the epidemiology and
      characteristics of nosocomial infections acquired in a tertiary care ICU and the
      impact of the various risk factors in their causation. MATERIALS AND METHODS: A
      retrospective study was conducted on the prospectively collected data of 153
      consecutive patients admitted in a tertiary care ICU between July 2014 and
      December 2015. The primary objective was to assess the epidemiology of ICU
      acquired bacterial infections in terms of the incidence of new infections,
      causative organism, and site. The secondary end point was to assess the risk
      factors for developing ICU-acquired infections. RESULTS: Out of the 153 patients
      enrolled in the study, 87 had an ICU-acquired nosocomial infection (58.86%). The
      most common organism responsible for infection was Klebsiella pneumoniae (37%),
      and the most common infection was pneumonia (33%). The duration of mechanical
      ventilation and length of ICU stay were significantly prolonged in patients
      developing nosocomial infections. There was no difference in mortality between
      the groups. The multivariate analyses identified intubation longer than 7 days,
      urinary catheterization >7 days, duration of mechanical ventilation more than 7
      days, and ICU length of stay longer than 7 days as independent risk factors for
      nosocomial infections. CONCLUSION: The study demonstrated a high incidence of
      nosocomial infection in the ICU and identified the risk factors for acquisition
      of nosocomial infections in the ICU.

PMID- 29033720
TI  - Reducing by 50% the incidence of maternal hypotension during elective caesarean
      delivery under spinal anesthesia: Effect of prophylactic ondansetron and/or
      continuous infusion of phenylephrine - a double-blind, randomized, placebo
      controlled trial.
AB  - BACKGROUND: Prophylactic administrations of ondansetron or phenylephrine have
      been reported to provide a protective effect against hypotension in women
      undergoing cesarean delivery under spinal anesthesia (SA). The main hypothesis is
      that ondansetron improves the hemodynamic response, especially combined with
      phenylephrine infusion. METHODS: This prospective, double-blind, randomized,
      placebo-controlled study included 265 healthy pregnant women scheduled for
      elective cesarean delivery under SA. Women were randomly allocated into four
      groups to receive either placebo (control), ondansetron (O) 8 mg intravenously
      before induction of SA, phenylephrine infusion (50 mcg/min) (P) or ondansetron
      plus phenylephrine (OP). Demographic, obstetric, intraoperative timing, and
      anesthetic variables were assessed at 16 time points. Anesthetic variables
      assessed included blood pressure, heart rate, oxygen saturation, nausea,
      vomiting, electrocardiographic changes, skin flushing, discomfort or pruritus,
      and vasopressor requirements. RESULTS: There were differences (P = 0.0001) in the
      number of patients with hypotension (50.8% control, 44.6% O, 20.9% P, 25.0% OP),
      the percentage of time points (P = 0.0001) with systolic hypotension per patient
      (17.4% control, 8.7% O, 2.1% P, 6.7% OP) and the number of patients requiring
      supplementary boluses of ephedrine (P = 0.003), phenylephrine (P = 0.017) or
      atropine (P = 0.0001). CONCLUSIONS: A 50 MUg/min phenylephrine infusion reduces
      by 50%, the incidence of maternal hypotension compared with placebo, but
      infusions of phenylephrine are still not routine in our environment. Prophylactic
      ondansetron 8 mg might be considered in this situation, because it does not
      reduce the incidence of maternal hypotension but diminishes its severity,
      reducing the number of hypotensive events per patient by 50%.

PMID- 29033721
TI  - An audit of in-hospital cardiopulmonary resuscitation in a teaching hospital in
      Saudi Arabia: A retrospective study.
AB  - OBJECTIVES: Data reflecting cardiopulmonary resuscitation (CPR) efforts in Saudi
      Arabia are limited. In this study, we analyzed the characteristics, and estimated
      the outcome, of in-hospital CPR in a teaching hospital in Saudi Arabia over 4
      years. METHODS: A retrospective, observational study was conducted between
      January 2009 and December 2012 and included 4361 patients with sudden
      cardiopulmonary arrest. Resuscitation forms were reviewed. Demographic data,
      resuscitation characteristics, and survival outcomes were recorded. RESULTS: The
      mean +/- standard deviation age of arrested patient was 40 +/- 31 years. The
      immediate survival rate was 64%, 43% at 24 h, and 30% at discharge. The death
      rate was 70%. Respiratory type of arrest, time and place of arrest, short
      duration of arrest, witnessed arrest, the use of epinephrine and atropine
      boluses, and shockable arrhythmias were associated with higher 24-h survival
      rates. A low survival rate was found among patients with cardiac types of arrest,
      and those with a longer duration of arrest, pulseless electrical activity, and
      asystole. Comorbidities were present in 3786 patients with cardiac arrest and
      contributed to a poor survival rate (P < 0.001). CONCLUSIONS: The study confirms
      the findings of previously published studies in highly developed countries and
      provides some reflection on the practice of resuscitation in Saudi Arabia.

PMID- 29033722
TI  - Effect of intravenous phenylephrine infusion on dose requirement of intrathecal
      plain levobupivacaine for cesarean section: A placebo-controlled preliminary
      study.
AB  - BACKGROUND: Phenylephrine infusion has been shown to decrease rostral spread of
      plain and hyperbaric local anesthetic (LA) when compared to ephedrine infusion.
      However, it does not result in higher dose requirement of hyperbaric LA for
      cesarean section. There is no trial evaluating the effect of phenylephrine
      infusion on ED50 of a plain intrathecal LA. METHODS: Pregnant patients with term
      uncomplicated singleton pregnancy undergoing elective cesarean section were given
      combined spinal-epidural anesthesia. They received intrathecal plain
      levobupivacaine 0.5% in a dose decided by up-and-down sequential allocation
      method along with 25 MUg fentanyl. Intravenous infusion of phenylephrine (100
      MUg/ml) or normal saline was initiated immediately after intrathecal injection.
      Systolic arterial pressure <=0.8 times baseline was treated using rescue boluses
      of phenylephrine 50 MUg. RESULTS: Demographic, other patient and surgical
      characteristics were similar in the two groups. ED50 of intrathecal plain
      levobupivacaine was significantly greater in phenylephrine group (5.5 mg [95%
      confidence interval (CI): 5.1-5.9 mg]) compared to saline group (4.2 mg [95% CI:
      3.4-5.1 mg]) (P = 0.01). Maximum sensory level, time to achieve adequate block,
      Apgar scores, and umbilical artery pH were similar in both groups. Total
      phenylephrine dose and patients having significant bradycardia were lesser in the
      saline group. CONCLUSIONS: Intrathecal dose requirement of plain levobupivacaine
      is greater using phenylephrine infusion as compared to saline infusion with
      rescue phenylephrine boluses. When using phenylephrine as a variable dose regimen
      titrated to maintain blood pressure within 20% of baseline, the ED50 of plain
      levobupivacaine is 5.5 mg (95% CI: 5.1-5.9 mg).

PMID- 29033723
TI  - Postoperative pain management in patients undergoing thoracoscopic repair of
      pectus excavatum: A retrospective analysis of opioid consumption and adverse
      effects in adolescents.
AB  - INTRODUCTION: Although the Nuss procedure provides excellent cosmetic results for
      the correction of pectus excavatum, the provision of analgesia following such
      procedures can be challenging. METHODS: The current study retrospectively reviews
      our experience over a 2.5 year period with thoracic epidural analgesia (TE),
      paravertebral blockade (PVB), and intravenous opioids delivered via patient
      controlled analgesia (PCA) to provide postoperative analgesia. RESULTS: The study
      cohort included 30 patients (mean age = 15.6 +/- 1.5 years), 15 of whom were
      treated with PCA, 8 with TE, and 7 with PVB. There were no significant
      differences in pain scores between the 3 groups at any time point during the
      first 3 postoperative days. Compared to PCA, the PVB group had lower opioid
      consumption over the first 24 hours of hospitalization by 1.7 mg/kg morphine
      equivalents (95% CI of difference: 0.1, 3.3; p=0.035); but had higher opioid
      consumption by 2.0 mg/kg morphine equivalents than the TE group (95% CI of
      difference: 0.3, 3.7; p=0.024). There were no differences in opioid consumption
      between PVB and PCA or between PVB and TE at 48 or 72 hours. The number of
      intraoperative hypotension episodes was significantly lower in the PCA group when
      compared to the PVB group (p=0.001), with no difference between the PVB and TE
      groups. CONCLUSIONS: The use of regional anesthesia should be considered a viable
      option for the relief of postoperative pain in pediatric patients following the
      Nuss procedure albeit with a higher incidence of intraoperative hemodynamic
      effects. A randomized, prospective, study powered to compare all 3 techniques
      against one another would be necessary to confirm the significance of these
      findings.

PMID- 29033724
TI  - Comparison of laryngeal tube suction II and proseal LMATM in pediatric patients,
      undergoing elective surgery.
AB  - BACKGROUND: Supraglottic airway devices now have an established place in
      pediatric anesthesia practice. The laryngeal tube suction (LTS) II, a recent
      revision of the LTS, has very few studies evaluating its use in pediatric
      patients. The aim of this study was to compare insertion and ventilation profiles
      of the LTS-II size 2 and the ProSealTM Laryngeal Mask Airway (PLMA) size 2 in
      pediatric patients undergoing elective surgeries. MATERIALS AND METHODS: A
      randomized prospective study was conducted in 100 children aged 2-5 years between
      12 and 25 kg weight, of the American Society of Anesthesiologists physical status
      I and II scheduled for routine elective surgeries of <90 min duration. They were
      randomly divided into two groups of 50 each, depending on the device inserted,
      and a standard protocol for anesthesia was followed. Outcome measures were
      studied in terms of ease and time of insertion, oxygen saturation (SpO2),
      oropharyngeal seal pressure (OSP), and ventilation failures. RESULTS: Both groups
      were well matched in terms of age, weight, and type of surgery. The success rate
      for the first attempt was 90% for both the LTS-II group and PLMA group. Insertion
      was found to be easy in the majority of cases in both groups, and there was no
      statistical difference in blood pressure, heart rate, or SpO2 on insertion.
      However, the OSP was significantly more in LTS-II and PLMA (P < 0.001). There
      were no clinically important complications in the postoperative period.
      CONCLUSIONS: Pediatric size 2 LTS-II is easy to insert and provides higher OSP
      compared with same size PLMA in anesthetized and paralyzed children undergoing
      elective surgery. It is a safe alternative to PLMA in short duration elective
      surgeries and may be a better device as it provides for higher OSPs.

PMID- 29033725
TI  - Assessment of patient-controlled analgesia versus intermittent opioid therapy to
      manage sickle-cell disease vaso-occlusive crisis in adult patients.
AB  - BACKGROUND: Vaso-occlusive crisis (VOC) is one of the acute complications of
      sickle-cell disease (SCD). Treatment mainly relies on hydration and pain control
      by analgesics. The specific aim of this study was to assess potential health
      outcomes within the first 72 h of admission between intermittent and patient
      controlled analgesia (PCA) by opioids among VOC patients. METHODS: A
      retrospective chart review study was conducted to determine SCD patients with
      VOC. Using the hospital electronic system, the following data were collected:
      patient's age, gender, blood pressure, heart rate, respiratory rate, oxygen
      saturation, and pain score on admission and daily for 3 days as well as the
      cumulative opioid analgesic dose for 72 h which is reported as morphine
      equivalent. RESULTS: One hundred and seventeen patients were screened over a
      period of 5 years. Of those, 99 (84.6%) met the study inclusion criteria, and 18
      patients (15.4%) were excluded from the study. During the first 72 h of
      admission, a significant reduction in pain score was observed in patients on
      intermittent intravenous (IV) administration compared to those in the PCA group
      (P < 0.0004) where the mean pain scores were 3 and 5, respectively. The total
      amount of morphine administered over 72 h of admission was significantly higher
      in PCA group (777 +/- 175 mg) as compared to the intermittent IV administration
      group (149 +/- 74 mg) (P < 0.000003). Clinically significant hypotension or
      respiratory depression was not observed in both groups over the 72 h of
      admission. CONCLUSION: During the first 72 h of admission, intermittent IV
      administration of morphine was more effective than PCA infusion in pain control.

PMID- 29033726
TI  - Ultrasound-guided multilevel paravertebral block versus local anesthesia for
      medical thoracoscopy.
AB  - BACKGROUND: Local anesthetic infiltration for medical thoracoscopy has an
      analgesic properties for short duration. Single injection thoracic paravertebral
      block (PVB) provides limited analgesia. PURPOSE: Comparison between thoracic PVB
      performed at two or three levels with local infiltration for anesthetic adequacy
      in adult medical thoracoscopy as a primary outcome and postthoracoscopic
      analgesia and pulmonary function as secondary outcomes for adult medical
      thoracoscopy. PATIENTS AND METHODS: Prospective randomized control study included
      63 adult patients with exudative pleural effusion randomly divided into three
      groups of 21 patients: 3-level PVB, 2-level PVB group, and local infiltration
      group. Patients with contraindications to regional anesthesia or uncontrolled
      comorbidities were excluded from the study. Pain visual analog scale and
      spirometry were used for comparison as anesthetic adequacy in adult medical
      thoracoscopy as a primary outcome besides prolonged analgesia and improved
      pulmonary function as secondary outcomes. RESULTS: The anesthetic adequacy was
      95.3% in 3-level PVB group, 81% in 2-level PVB group, and 71.5% in local
      infiltration group. The mean sensory level was 1 +/- 0.8 and 1 +/- 0.6 segment
      above and 0.8 +/- 0.6 and 0.7 +/- 0.7 segment below the injected level in 3-level
      PVB group and 2-level PVB, respectively. VAS was statistically significant higher
      in local infiltration compared to the other two groups immediately
      postthoracoscopic and 1 h after. Two-hour postthoracoscopy, significant increase
      in forced vital capacity values in the three groups compared to their basal
      values whereas forced expiratory volume at 1 s (FEV1) only in both PVB groups.
      CONCLUSION: Unilateral 3-level TPVB was superior to 2-level TPVB and LA
      infiltration for anesthetic adequacy for patients undergoing medical
      thoracoscopy. Moreover, US-guided TPVB was followed by higher FEV1 values and
      lower pain scores during the next 12 h postthoracoscopy in comparison to local
      infiltration, so 3-level TPVB is an effective and relatively safe anesthetic
      technique for adult patients undergoing medical thoracoscopy which may replace
      local anesthesia.

PMID- 29033727
TI  - Ultrasound assessment of cranial spread during caudal blockade in children:
      Effect of different volumes of local anesthetic.
AB  - BACKGROUND: Ultrasound-guided caudal block injection is a simple, safe, and
      effective method of anesthesia/analgesia in pediatric patients. The volume of
      caudal drug required has always been a matter of debate. MATERIALS AND METHODS:
      This present prospective, randomized, double-blinded study aimed to measure
      extent of the cranial spread of caudally administered levobupivacaine in Indian
      children by means of real-time ultrasonography. Ninety American Society of
      Anesthesiologists I/II children scheduled for urogenital surgeries were enrolled
      in this trial. Anesthesia and caudal analgesia were administered in a
      standardized manner in the patients. The patients received 0.5 ml/kg or 1 ml/kg
      or 1.25 ml/kg of 0.125% levobupivacaine according to the group allocated. Cranial
      spread of local anesthetic was noted using ultrasound. RESULTS: There was no
      difference in the spread when related to age, sex, weight, or body mass index. A
      significant difference of ultrasound-assessed cranial spread of the local
      anesthetic was found between Group 1 (0.5 ml/kg) with both Group 2 (1 ml/kg) (P =
      0.001) and with Group 3 (1.125 ml/kg) (P < 0.001) but there is no significant
      difference between Group 2 and Group 3 (P = 0.451) revealing that spinal level
      spread is only different between 0.5 ml/kg and 1 ml/kg of local anesthetic.
      CONCLUSION: In conclusion, the ultrasound assessment of local anesthetic spread
      after a caudal block showed that cranial spread of the block is dependent on the
      volume injected into the caudal space. Since there was no difference between 1
      ml/kg and 1.25 ml/kg, to achieve a dermatomal blockade up to thoracic level, we
      might have to increase the dose beyond 1.25 ml/kg, keeping the toxic dose in
      mind.

PMID- 29033729
TI  - Use of rocuronium and sugammadex under neuromuscular transmission monitoring in a
      patient with multiple sclerosis.
AB  - Multiple sclerosis (MS) is a potentially disabling disease characterized by
      demyelinating lesions in the central nervous system. One of the anesthetic
      challenges encountered in surgical patients with MS is the management of
      neuromuscular blockade (NMB) and its reversal. We report a case of a 31-year-old
      female patient suffering from MS, who underwent gynecological surgery under
      general anesthesia with sevoflurane, fentanyl, and rocuronium which was
      successfully reversed with sugammadex. Neuromuscular transmission (NMT)
      monitoring was used to guide the intraoperative doses of rocuronium and also the
      reversal of NMB by the use of sugammadex to ensure a safe tracheal extubation. In
      addition, delivered volatile was titrated according to anesthetic depth
      monitoring (Bispectral Index) while esophageal temperature was also monitored for
      the maintenance of normothermia. Postoperatively, a multimodal analgesic scheme
      offered a high-quality analgesia and sleep, minimization of anxiety, and
      increased patient satisfaction. At 1-month follow-up, the patient's course was
      uncomplicated without any MS exacerbation. We consider that the use of rocuronium
      and sugammadex under NMT monitoring may represent a useful and safe choice in
      patients with MS.

PMID- 29033730
TI  - Intentional intra-arterial injection of midazolam in a patient with status
      epilepticus in the Intensive Care Unit.
AB  - Fundamental medical care includes intravenous (IV) access which provides prompt
      resuscitation and reliable delivery of analgesics, antibiotics, and vasoactive
      medication. Difficult access populations, especially in critical area, continue
      to challenge providers to consider and utilize alternative means to provide IV
      access. Potential options under such circumstances include intramuscular,
      intraosseous, and intratracheal drug administration, but in extreme cases where
      no other options are available, intra-arterial route might be considered. We
      present a case where midazolam was intentionally injected intra-arterially to
      abort seizure activity in a patient with status epilepticus in the Intensive Care
      Unit.

PMID- 29033728
TI  - Anesthesia in pregnancy with heart disease.
AB  - Management of pregnant women with heart disease remains challenging due to the
      advancement of innovations in cardiac surgery and correction of complex cardiac
      anomalies, and more recently, with the successful performance of heart
      transplants, cardiac diseases are not only likely to coexist with pregnancy, but
      will also increase in frequency over the years to come. In developing countries
      with a higher prevalence of rheumatic fever, cardiac disease may complicate as
      many as 5.9% of pregnancies with a high incidence of maternal death. Since many
      of these deaths occur during or immediately following parturition, heart disease
      is of special importance to the anesthesiologist. This importance arises from the
      fact that drugs used for preventing or relieving pain during labor and delivery
      exert a major influence - for better or for worse - on the prognosis of the
      mother and newborn. Properly administered anesthesia and analgesia can contribute
      to the reduction of maternal and neonatal mortality and morbidity.

PMID- 29033731
TI  - Ultrasound-guided continuous spinal anesthesia for cesarean section in a
      parturient with scoliosis corrected with Harrington's rod surgery.
AB  - With rapid improvement in healthcare in Saudi Arabia, increasing number of women
      with surgically corrected kyphoscoliosis are likely to present for cesarean
      section (CS) or vaginal delivery requiring anesthesia or analgesia. Despite the
      surgical correction, these patients have poor cardiopulmonary reserves which
      increase the risks associated with general anesthesia. Whereas altered vertebral
      anatomy from previous surgery and the presence of metal work in spine make
      performing of regional anesthesia (RA) difficult and unpredictable, we report
      anesthetic management of such a patient who underwent CS using continuous spinal
      anesthesia technique. Challenges of placement of a spinal catheter in such a
      patient are discussed, and use of ultrasonography to circumnavigate these
      challenges is described. We propose that ultrasound can prove extremely valuable
      in performing of RA in patients with surgically corrected kyphoscoliosis. We
      could not find a similar case report from Saudi Arabia in the published
      literature.

PMID- 29033732
TI  - Double aortic arch presenting with respiratory distress: A case report and review
      of the literature.
AB  - Tracheal compression by vascular structures in infants is uncommon and may be
      masked by nonspecific respiratory symptoms. Double aortic arch (DAA) is the most
      common vascular ring. We describe a case of a 9-month-old male infant presented
      with respiratory distress and found to have a DAA. In this report, the authors
      emphasize the consideration of this pathology-induced respiratory distress and
      discuss its anesthetic management.

PMID- 29033733
TI  - Anesthesia management for a case of laryngeal keel placement.
AB  - Congenital laryngeal web is a rare anomaly with incidence of 1 in 10,000 births.
      Its clinical presentation may range from an asymptomatic patient or mild
      hoarseness of voice to severe respiratory stridor. The primary goals of surgical
      intervention for congenital laryngeal web are to establish a patent airway and to
      achieve a good voice quality. As recurrence rate after plain excision of
      laryngeal web is very high, its removal may be coupled by placement of a silastic
      keel in between vocal cords. Endolaryngeal placement of a keel is definitely less
      invasive than laryngofissure, but little is known about its anesthesia
      management. Frequent ventilatory adjustment and endotracheal tube (ETT)
      manipulations are needed along with vigilant monitoring. Risk of perforation or
      accidental dislodgment of the ETT and laryngeal edema are other concerns in
      management. We report a case.

PMID- 29033734
TI  - Microlaryngeal endotracheal tube for lung isolation in pediatric patient with
      significant tracheal narrowing.
AB  - A 15-year-old boy, weighing 45 kg, 160 cm height with large anterior mediastinal
      mass and significant tracheal narrowing was scheduled for thoracotomy and
      excision of the mass. He had a history of progressive dyspnea, inability to lie
      supine, and a right upper hemithorax mass 13 cm * 13 cm * 11 cm as evident on a
      computerized tomography with significant compression of the trachea and right
      main stem bronchus. Inhalational induction was carried out using sevoflurane with
      100% oxygen. After achieving adequate depth of anesthesia with the maintenance of
      spontaneous respiration with oxygen and sevoflurane (minimum alveolar
      concentration 1.7), left principal bronchus was intubated under fiber-optic
      bronchoscopy, with 5 mm cuffed microlaryngeal surgery tube. Excellent lung
      isolation was achieved. Selection of endotracheal tube for lung isolation and
      endobronchial intubation in the presence of significant tracheal narrowing are
      discussed.

PMID- 29033735
TI  - Intramyometrial vasopressin: A fear for anesthetist?

PMID- 29033737
TI  - A very rare unusual site of ventilator breathing circuit leakage: Beware!!

PMID- 29033736
TI  - Avoiding failed spinal anesthesia: "Advik technique".

PMID- 29033738
TI  - Magill forceps: A savior in bronchoscopy.

PMID- 29033739
TI  - Intravenous burn following accidental warm saline infusion.

PMID- 29033740
TI  - Child with Edward's syndrome for radiological procedure: An anesthetic challenge.

PMID- 29033741
TI  - Ventricular laryngeal cyst: A threat to airway!

PMID- 29033742
TI  - Gum elastic bougie as a guide in nasotracheal intubation: A novel technique.

PMID- 29033743
TI  - Splanchnic nerve radiofrequency ablation for treating resistant abdominal pain.

PMID- 29033744
TI  - Pulsed radiofrequency of the supraorbital nerve for the treatment of supraorbital
      neuralgia.

PMID- 29033745
TI  - Using angle connector? Be careful: A hazard note.

PMID- 29033746
TI  - Concealed kinking of pediatric flexometallic tube at fixation point.

PMID- 29033747
TI  - Craniopagus twins for magnetic resonance imaging.

PMID- 29033748
TI  - Arm position-dependent kinking of intravenous cannula.

PMID- 29033749
TI  - "Two-hand-manoeuver" during nasotracheal intubation.

PMID- 29033750
TI  - Bilateral quadratus lumborum block for postoperative analgesia in a Von Hippel
      Lindau syndrome patient undergoing laparoscopic radical nephrectomy.

PMID- 29033751
TI  - "Curare crest" can detect breakthrough breathing.

PMID- 29033752
TI  - Anesthetic management of craniopagus conjoined twins in a remote location.

PMID- 29033753
TI  - Use the natural curve of the nasogastric tube: A simple technique of insertion.

PMID- 29033754
TI  - Retroclavicular approach of brachial plexus block: Here to stay!!!

PMID- 29033755
TI  - A rare case of submitral left ventricular aneurysms.

PMID- 29033756
TI  - Progression from an Inflammatory to a Fibrostenotic Phenotype in Eosinophilic
      Esophagitis.
AB  - Previous studies have suggested that eosinophilic esophagitis (EoE) progresses
      from chronic inflammation to fibrostenosis. However, natural history data
      illustrating this progression in individual patients are lacking. Here, we
      present 6 patients who progressed from an inflammatory to a fibrostenotic
      phenotype of EoE in the absence of treatment. At the time of diagnosis, none of
      the patients had significant evidence of fibrostenosis, but they did have other
      inflammatory findings of EoE such as edema, linear furrows, or exudates. After
      being lost to follow-up and treatment for an average of 7.8 +/- 2.0 years,
      strictures (n = 5; 83%) or a small-caliber esophagus (n = 4; 67%) were present in
      a majority of the patients, and the majority required esophageal dilation. These
      cases confirm that EoE can progress from an inflammation-only phenotype to a
      fibrostenotic phenotype in certain patients.

PMID- 29033757
TI  - Gallstone Ileus: An Unlikely Cause of Mechanical Small Bowel Obstruction.
AB  - Gallstone ileus is a rare disease that accounts for 1-4% of intestinal
      obstructions. Almost exclusively a condition in the older female population, it
      is a difficult diagnosis to make. We report the case of gallstone ileus in a 94
      year-old Caucasian female, who presented to the emergency department with acute
      onset nausea, coffee-ground emesis, lack of bowel movement, and abdominal
      distension. On CT scan, the diagnosis of gallstone ileus was made by the presence
      of a cholecystoduodenal fistula, pneumobilia, and small bowel obstruction.
      Emergent laparotomy with a one-stage procedure of enterolithotomy and stone
      removal by milking the bowel distal to the stone were performed. The
      postoperative course was uneventful until postoperative day 4 when the patient
      was found tachycardic, lethargic, and unresponsive. We reviewed the literature on
      the diagnosis and treatment of gallstone ileus.

PMID- 29033758
TI  - Resection of Locally Advanced Pancreatic Neoplasms after Neoadjuvant Chemotherapy
      with Nab-Paclitaxel and Gemcitabine following FOLFIRINOX Failure.
AB  - The incidence of pancreatic cancer has dramatically increased over the past
      years, but the prognosis has not improved. Between 30 and 40% of tumors are
      considered locally advanced, essentially due to vascular involvement. In recent
      years, new chemotherapy protocols with high response rates have been developed.
      FOLFIRINOX seems to be an interesting option in this situation, but hematologic
      toxicity could be an obstacle to its prescription. Nab-paclitaxel and gemcitabine
      offer significant response rates with a reasonable safety profile. We report here
      a single-center experience of 2 cases with a locally advanced pancreatic cancer
      initially considered unresectable, progressive after first-line neoadjuvant
      FOLFIRINOX chemotherapy, and then treated with second-line nab
      paclitaxel/gemcitabine chemotherapy.

PMID- 29033759
TI  - Sump Syndrome: A Rare Long-Term Complication of Choledochoduodenostomy.
AB  - Biliary sump syndrome is a rare condition. It is seen as a rare long-term
      complication in patients with a history of a side-to-side choledochoduodenostomy.
      In the era before endoscopic retrograde cholangiopancreatography, side-to-side
      choledochoduodenostomy was a common surgical procedure for the management of
      biliary obstruction. In the setting of a side-to-side choledochoduodenostomy, the
      bile does not drain through the distal common bile duct anymore. Therefore, the
      part of the common bile duct distal from the choledochoduodenostomy anastomosis
      consequently transforms into a poorly drained reservoir, making this so-called
      "sump" prone to accumulation of debris. These patients are prone to cholangitis.
      We present a 64-year-old man with a history of side-to-side
      choledochoduodenostomy who presented with manifestations of cholangitis. An
      endoscopic retrograde cholangiopancreatography confirmed a diagnosis of sump
      syndrome. The etiology, clinical manifestations, and treatment of biliary sump
      syndrome are discussed in this article.

PMID- 29033760
TI  - Colonic Ganglioneuroma: A Rare Finding during Colorectal Cancer Screening.
AB  - Ganglioneuromas are very rare clinical entities, and their occurrence in the
      large bowel lays further emphasis on their rarity. Ganglioneuromas are benign
      tumors of undifferentiated neural crest cells. Their clinical presentation is
      mostly asymptomatic, and if any symptoms are present at all, they are usually
      nonspecific, with excellent prognosis. We report an asymptomatic, 65-year-old
      male with a solitary ascending colonic polyp found on screening colonoscopy.
      Histology revealed benign polypoid spindle-cell proliferation as well as S100
      reactivity, consistent with ganglioneuroma. We report on the clinical
      presentation and discuss the origin, epidemiology, treatment, and management of
      this lesion.

PMID- 29033762
TI  - Typhoid Fever and Acute Appendicitis: A Rare Association Not Yet Fully Formed.
AB  - Infections caused by foodborne enteric pathogens including typhoidal and non
      typhoidal Salmonella species can mimic symptoms of acute appendicitis. The
      association between such bacterial pathogens and pathology-proven acute
      appendicitis has been described, but this link is poorly understood. Here we
      describe a case of a young man with typhoid fever presenting with histology
      proven acute appendicitis requiring urgent appendectomy, and provide a brief
      review of relevant literature to prompt more widespread recognition of this rare
      cause of a common surgical emergency.

PMID- 29033761
TI  - Drug-Induced Autoimmune Hepatitis following Treatment with Zoledronic Acid.
AB  - Adverse drug reactions are among the most frequent side effects of synthetic and
      complementary alternative drugs and represent the premier causes of license
      revocations and acute liver failure. Drug-induced liver injury can resemble
      literally any other genuine liver disease and usually responds well to drug
      dechallenge. However, in some cases autoimmune-like hepatitis can evolve,
      requiring short- and sometimes long-term immunosuppression. Here, we present the
      hitherto first case of autoimmune-like hepatitis following treatment with
      zoledronic acid.

PMID- 29033763
TI  - Multiple Small Intestine Ulcers with Desquamation of the Fingers.
AB  - A 73-year-old female was admitted to our hospital with abdominal pain and
      diarrhea. Computed tomography detected distension of the small intestine. A
      palmar erythema, multiple oral ulcers, and desquamation of the fingers appeared
      after hospitalization. Small-bowel endoscopic images showed multiple ulcers. We
      attributed this case to infection with Yersinia pseudotuberculosis based on the
      changes in Y. pseudotuberculosis antibody titers throughout the course of the
      illness. This report is valuable, as it illustrates the endoscopic
      characteristics of a Y. pseudotuberculosis infection with skin lesion and ileus,
      which may enable us to deepen the pathologic understanding of this disease.

PMID- 29033764
TI  - Non-Meckel Small Intestine Diverticulitis.
AB  - Non-Meckel small intestine diverticulitis can have many manifestations and its
      management is not well-defined. We report 4 unselect cases of small intestine
      diverticulitis; all patients were seen by the same physician at the Emergency
      Center at The University of Texas MD Anderson Cancer Center between 1999 and
      2014. The median age at diagnosis of these patients was 82 years (range, 76-87
      years). All 4 patients presented with acute onset of abdominal pain, and computed
      tomography scans showed characteristics of small intestine diverticulitis
      unrelated to cancer. Most of the diverticula were found in the region of the
      duodenum and jejuno-ileal segments of the small intestine. The patients, even
      those with peripancreatic inflammation and localized perforation, were treated
      conservatively. Non-Meckel diverticulitis can be overlooked in the initial
      diagnosis because of the location of the diverticulosis, the age of the patient,
      and the rarity of the disease. Because patients with non-Meckel small intestine
      diverticulitis can present with acute abdominal pain, non-Meckel small intestine
      diverticulitis should be considered in the differential diagnosis of patients
      with acute abdominal pain, and computed tomography scans can help identify the
      condition. Because of the rarity of non-Meckel small intestine diverticulitis,
      few studies have been published, and the data are inconclusive about how best to
      approach these patients. Our experience with these 4 elderly patients indicates
      that non-Meckel small intestine diverticulitis can be treated conservatively,
      which avoids the potential morbidity and mortality of a surgical approach.

PMID- 29033765
TI  - Celiac Disease Associated with a Benign Granulomatous Mass Demonstrating Self
      Regression after Initiation of a Gluten-Free Diet.
AB  - Celiac disease is a chronic immune-mediated enteropathy in which dietary gluten
      induces an inflammatory reaction predominantly in the duodenum. Celiac disease is
      known to be associated with benign small bowel thickening and reactive
      lymphadenopathy that often regresses after the institution of a gluten-free diet.
      A 66-year-old male patient with celiac disease presented with abdominal pain and
      diarrheal illness. Computerized tomography of the abdomen revealed a duodenal
      mass. Endoscopic ultrasound-guided fine needle aspiration of the mass revealed
      bizarre stromal cells which represent a nonspecific tissue reaction to
      inflammation. This inflammatory mass regressed after the institution of a gluten
      free diet. This case report describes a unique presentation of celiac disease in
      the form of a granulomatous self-regressing mass. Also, this is the first
      reported case of bizarre stromal cells found in association with celiac disease.
      In addition to lymphoma and small bowel adenocarcinoma, celiac disease can
      present with a benign inflammatory mass, which should be serially monitored for
      resolution with a gluten-free diet.

PMID- 29033766
TI  - Effect of Oral Care Gel for Burning Mouth Syndrome in a Patient with Hepatitis C:
      A Case Report.
AB  - Burning mouth syndrome (BMS) is a burning sensation in the mouth with no
      underlying dental or medical cause. To date, there is no satisfactory treatment
      for BMS. Herein, we present the case of a 42-year-old female presenting with
      hepatitis C virus infection along with BMS. Despite two interferon therapies and
      a sustained virologic response, the discomfort in her oral mucosa persisted. At
      the age of 51, the patient complained of burning sensation and tingling pain in
      the tongue; a thin layer of REFRECARE-H(r), an oral care gel (therapeutic
      dentifrice), was applied on the oral membrane after each meal for 60 days.
      Application of REFRECARE-H(r) decreased the various symptoms including tingling
      pain, oral discomfort, breath odor, sleep disorder, depressive mood, and
      jitteriness. The improvement in quality of life continued for 30 days after
      application of the gel. These findings indicate that REFRECARE-H(r) may be
      effective in reducing the symptoms associated with BMS. Long-term follow-up
      studies with larger number of patients are required to elucidate the therapeutic
      effects of this gel.

PMID- 29033767
TI  - Hemorrhagic Cholecystitis in a Patient on Maintenance Dialysis.
AB  - The present paper describes a case of hemorrhagic cholecystitis in a patient on
      maintenance dialysis. The patient presented with right upper quadrant abdominal
      pain. Computed tomography revealed swelling of the gallbladder, high- and
      isodensity contents of the gallbladder, and high-density stone in the gallbladder
      neck. He was hospitalized for suspected acute cholecystitis. After
      hospitalization, his levels of total bilirubin, aspartate aminotransferase, and
      alanine aminotransferase increased. T2-weighted magnetic resonance imaging showed
      low-intensity contents expanded to include a wide area from the common bile duct
      to the cystic duct and gallbladder neck. Endoscopic retrograde
      cholangiopancreatography revealed clotting from the duodenal papilla. After
      cannulation of the bile duct, old blood and pus began to flow from the mammary
      papilla, and an endoscopic nasobiliary drainage tube was placed. After his liver
      function had improved, the patient underwent laparoscopic cholecystectomy. His
      sample revealed that the gallbladder was filled with blood clots and stones. His
      postoperative course was uneventful and he was discharged on day 19 after the
      procedure. Although hemorrhagic cholecystitis is rare, it should be considered as
      a differential diagnosis for patients on dialysis who have acute abdominal
      symptoms.

PMID- 29033768
TI  - Preoperative Diagnosis of Intestinal Endometriosis by Magnifying Colonoscopy and
      Target Biopsy.
AB  - Endometriosis can affect any portion of the gastrointestinal tract. A
      preoperative definitive diagnosis of intestinal endometriosis is difficult,
      because there is no characteristic endoscopic finding and the endoscopic biopsies
      usually sample insufficient endometrial tissue for pathologic diagnosis. To our
      knowledge, the magnifying endoscopic features of intestinal mucosal endometriosis
      have not been well documented. In this study, we report a case of intestinal
      endometriosis diagnosed preoperatively by magnifying image-enhanced colonoscopy
      and target biopsy. A 45-year-old woman was referred to our hospital with
      abdominal pain in the left lower quadrant. Colonoscopy showed a submucosal tumor
      like lesion of approximately 30 mm in diameter exhibiting surface reddening and
      granular changes in the sigmoid colon. Magnifying endoscopy revealed sparsely
      distributed round pits in the granules. The mucosal biopsy specimen from the
      granule provided the diagnosis of intestinal endometriosis. Segmental
      sigmoidectomy was performed, and pathological examination revealed that the
      surface colonic mucosa was partially replaced by endometrial tissue, which
      accounted for the granular change detected in the colonoscopy. It can be
      speculated that the round pit might reflect the endometrial glands surrounded by
      endometrial stroma. This case illustrated the characteristic finding and utility
      of magnifying endoscopy for mucosal intestinal endometriosis.

PMID- 29033769
TI  - Ascending Cholangitis due to Heavy Lifting.
AB  - Gallstone disease is the most common risk factor for cholangitis. In an
      anatomically normal bile duct system, cholangitis does not occur without the
      presence of stones. Endoscopic retrograde cholangiography with papillotomy and
      stone extraction is a well-established curative therapy for gallstones in the
      common bile duct. More important, papillotomy prevents recurrent episodes. The
      present case report describes a 73-year-old male with recurring cholangitis in a
      clear bile duct system after previous papillotomy. An etiology of duodenal reflux
      into the common bile duct due to heavy lifting is proposed.

PMID- 29033770
TI  - Acinar Cell Cystadenocarcinoma of the Pancreas.
AB  - Acinar cell cystadenocarcinoma is a rare malignant epithelial neoplasm of the
      pancreas with a diffusely cystic, gross architecture in which the cysts are lined
      with neoplastic epithelial cells that demonstrate evidence of pancreatic exocrine
      enzyme production. This is the 10th case that has been reported in the
      literature. A 77-year-old male complaining of left hypochondrial pain was
      referred to our hospital for treatment of a pancreatic tumor. A huge, honeycomb
      structured tumor was detected in the pancreatic tail. Distal pancreatectomy with
      total resection of the residual stomach and partial resection of the transverse
      colon were performed. Microscopically, there were variably sized cystic lesions
      in the tumor. Immunohistochemical examinations revealed that tumor cells were
      positive for alpha 1-antichymotrypsin and alpha 1-trypsin, showing that tumor
      cells had features of pancreatic acinar cells. Thus, the tumor was diagnosed as
      acinar cell cystadenocarcinoma. Herein, we report a rare case with acinar cell
      cystadenocarcinoma, which is the 10th case reported in the literature based on a
      PubMed search. We managed to resect the tumor completely by distal pancreatectomy
      with total resection of the residual stomach and partial resection of the
      transverse colon. The patient is still alive 26 months after surgery without any
      recurrence after 1 year of adjuvant chemotherapy with S-1.

PMID- 29033771
TI  - Malignant Gastric Outlet Obstruction from Pancreatic Cancer.
AB  - Patients with advanced-stage pancreatic cancer are typically burdened by many
      symptoms that impair functioning and worsen quality of life. We report an
      exceptional case of a 73-year-old woman with T4N1M0 adenocarcinoma of the
      uncinate process of the pancreas who developed significant gastric outlet
      obstruction - an uncommon yet potentially life-threatening complication of
      disease progression. She developed progressive abdominal pain and emesis, and
      profound dilatation of her stomach was detected on a radiation therapy simulation
      CT scan that required urgent decompression. Malignant gastric outlet obstruction
      must be included in the differential diagnosis when patients with known advanced
      disease of the pancreas present with obstructive upper gastrointestinal symptoms.

PMID- 29033772
TI  - Intraparenchymal Hemorrhage due to Brain Metastasis of Hepatocellular Carcinoma.
AB  - Although extrahepatic metastases from hepatocellular carcinoma (HCC) are present
      in only 5-15% of cases, they are certainly factors associated with poor
      prognosis. The main sites include lung, lymph nodes, bones, and adrenal glands,
      in descending order. Metastasis in the central nervous system is extremely rare,
      and the incidences vary from 0.6 to 1.7%. We report a case of a 54-year-old man
      previously diagnosed with alcohol-induced cirrhosis of the liver and HCC. The
      patient was admitted presenting progressive left hemiparesis and headache which
      started 2 days earlier, with no history of cranioencephalic trauma. After
      admission, cranial computed tomography revealed an intraparenchymal hemorrhage
      area with surrounding edema in the right frontal lobe. An angioresonance
      requested showed a large extra-axial mass lesion located in the right frontal
      region with well-defined contours and predominantly hypointense signal on T2
      sequence. At first, the radiological findings suggested meningioma as the first
      diagnostic hypothesis. However, the patient underwent surgery. The tumor was
      completely removed, and the morphological and immunohistochemical findings were
      consistent with metastatic hepatocarcinoma associated with meningioma. In
      postoperative care, the patient did not recover from the left hemiparesis and
      manifested Broca's aphasia. He had a survival time of 24 weeks, presenting acute
      liver failure as his cause of death. There is a lack of evidence supporting a
      specific management of patients with brain metastasis from HCC. Furthermore,
      there are no studies that evaluate different modalities of therapeutics in brain
      metastasis of HCC due to the rarity of this condition. Therefore, management must
      be individualized depending on probable prognostic factors in these patients.

PMID- 29033773
TI  - Laparoscopic Resection of a Jejunal Mesenteric Pseudocyst.
AB  - An unusual case of a jejunal mesenteric pseudocyst treated by laparoscopic
      resection is reported. A 44-year-old woman was admitted to our hospital with
      intermittent upper abdominal pain and diarrhea. Physical examination revealed
      slight periumbilical tenderness, and no masses were palpable. Contrast-enhanced
      computed tomography showed a 4-cm-sized nonenhancing high-density mass with a
      heterogeneous pattern on a proximal small bowel loop. Based on these findings, a
      gastrointestinal stromal tumor accompanied by hemorrhagic and cystic change, a
      mesenteric hematoma, or a desmoid tumor was diagnosed. Laparoscopy was performed
      to obtain an accurate diagnosis. Exploration of the abdominal cavity identified a
      4-cm mass originating from the mesentery of the jejunum. Segmental resection of
      the jejunum and its mesentery, including the mass, was performed.
      Macroscopically, the mass appeared to be a cystic mass of the jejunal mesentery.
      The mass within the cyst lumen consisted of white clayish material with no
      specific pathology. The final pathological diagnosis was a mesenteric pseudocyst.
      The patient had an uneventful postoperative course.

PMID- 29033774
TI  - Hemothorax following Uncomplicated Endoscopic Variceal Sclerotherapy and Ligation
      for Esophageal Varices.
AB  - Endoscopic variceal sclerotherapy and ligation are standard treatment modalities
      used for the management of esophageal varices. Reportedly, sclerotherapy and
      ligation are associated with complications such as hematuria, pulmonary thrombus
      formation, pleural effusion, renal dysfunction, and esophageal stenosis. However,
      hemothorax following sclerotherapy and ligation has not yet been reported. We
      treated a patient who presented with liver cirrhosis and polycythemia vera and
      later developed hemothorax following the above-mentioned procedures. An 86-year
      old man diagnosed with liver cirrhosis due to chronic hepatitis type B and
      alcohol abuse underwent variceal sclerotherapy using ethanolamine oleate to treat
      his esophageal varices. Oozing from the esophageal varices continued even after
      the sclerotherapy procedure; therefore, we performed endoscopic variceal
      ligation. The patient developed left-sided hemothorax within 24 h after treatment
      of his varices, and an emergency thoracotomy was performed. A pulmonary ligament
      of the left lung was bulging and ripping because of mediastinal hematoma, and
      oozing was noted. Cessation of bleeding was noted after the laceration of the
      left pulmonary ligament had been sutured. Ours is the first case of hemothorax
      reported in a patient following an uncomplicated procedure of sclerotherapy and
      ligation.

PMID- 29033776
TI  - Carbohydrate Antigen 19-9-Positive Gastric Adenocarcinoma: Autopsy Findings and
      Review of the Literature.
AB  - Carbohydrate antigen 19-9 (CA19-9) is a well-known tumor marker for
      pancreatobiliary cancer, and several studies have shown that an elevated serum
      CA19-9 level is associated with more aggressive biological behavior in gastric
      cancer (GC). However, the clinicopathological characteristics of CA19-9-positive
      GC remain unclear. We herein report an autopsy case of CA19-9-positive GC in an
      84-year-old man who was admitted to our hospital because of paralysis and anemia.
      Autopsy revealed an ulcerative-invasive tumor measuring 72 * 60 mm in the
      anterior wall of the gastric body. The tumor had invaded beyond the muscularis
      propria, and metastasized to the lung, liver, and regional lymph nodes.
      Histologically, the tumor cell had oval nuclei with abundant clear cytoplasm, and
      tubular and/or papillary features with prominent lymphovascular permeation and
      perineural invasion, mimicking pancreatobiliary carcinoma. Immunohistochemically,
      the tumor cells showed diffuse immunopositivity for CA19-9 and carcinoembryonic
      antigen. According to a review of cases reported in the literature, CA19-9
      positive GCs show clinicopathological characteristics such as antral location,
      ulcerative-infiltrating gross feature, differentiated histology, prominent
      lymphatic and venous invasion, higher proportion of metastasis, and higher
      clinical stage. These results suggest that CA19-9-positive GC is pathologically a
      distinctive type of tumor with aggressive biological behavior.

PMID- 29033775
TI  - Preoperative Diagnosis and Surgical Approach of Appendiceal Mucinous Cystadenoma:
      Usefulness of Volcano Sign.
AB  - We report a case of appendiceal mucinous cystadenoma that was successfully
      diagnosed preoperatively and treated by laparoscopic resection. We could find
      volcano sign on colonoscopy and cystic lesion without any nodules at the appendix
      on computed tomography (CT). Without any malignant factors in preoperative
      examinations, we performed laparoscopic appendectomy including the cecal wall. We
      could avoid performing excessive operation for cystadenoma with accurate
      preoperative diagnosis and intraoperative finding and pathological diagnosis
      during surgery. Appendiceal mucocele is a rare disease that is divided into 3
      pathological types: hyperplasia, cystadenoma, and cystadenocarcinoma. The
      surgical approaches for it remain controversial and oversurgery is sometimes done
      for benign tumor, because preoperative diagnosis is difficult and rupturing an
      appendiceal tumor results in dissemination. Based on our study, volcano sign on
      colonoscopy and CT findings were important for the preoperative diagnosis of
      appendiceal mucocele. Furthermore, we think that laparoscopic resection will
      become a surgical option for the treatment of appendiceal mucocele.

PMID- 29033777
TI  - Unusual Clinical Presentation of Hemobilia with Recurrent Vasovagal Episodes.
AB  - Hemobilia is caused by the abnormal connection between a blood vessel and the
      bile duct, which is usually iatrogenic and caused by hepatobiliary procedures.
      The classic triad of hemobilia includes biliary colic, obstructive jaundice, and
      gastrointestinal bleeding. We present the case of an 80-year-old man who had
      laparoscopic cholecystectomy complicated by hemobilia. He had an unusual
      presentation of hemobilia in the form of transient vasovagal episodes in addition
      to abdominal pain and hematochezia.

PMID- 29033779
TI  - A Patient with Nafcillin-Associated Drug-Induced Liver Failure.
AB  - Nafcillin-induced acute liver injury is a rare and potentially fatal complication
      that has been known since the 1960s but inadequately studied. At this time, the
      only proven treatment is early discontinuation of the drug. Because of the high
      prevalence of nafcillin class antibiotic use in the United States, it is
      important for clinicians to have a high clinical suspicion for this diagnosis. We
      present a case of liver failure attributable to nafcillin use in a 68-year-old
      male with a history methicillin-sensitive Staphylococcus and L3/L4 osteomyelitis.
      After starting long-term antibiotic therapy, he presented with painless jaundice
      which necessitated discontinuation of the drug. At the time of presentation, the
      patient's lab work exhibited a bilirubin/direct bilirubin of 9.4/8.2 mg/dL,
      alkaline phosphatase of 311 IU/L, and aspartate transaminase/alanine transaminase
      of 109/127 IU/L. The patient was switched to i.v. vancomycin given the concern
      for drug-induced liver injury. Imaging did not show obstruction of the
      hepatobiliary or pancreaticobiliary trees. Serology was unremarkable for viral
      etiology, autoimmune processes, Wilson disease, and hemochromatosis. A liver
      biopsy showed findings consistent with drug-induced liver injury. The patient's
      liver function tests peaked at day 7 of admission and trended towards normal
      levels with cessation of nafcillin therapy. The patient was discharged with a
      diagnosis of nafcillin-induced acute liver injury. Our case highlights the
      importance of early recognition of the diagnosis and careful monitoring of liver
      function when nafcillin is employed in the clinical setting.

PMID- 29033778
TI  - A Case of Basaloid Squamous Cell Carcinoma of Polypoid Type in the Esophagus.
AB  - Basaloid squamous cell carcinoma of the esophagus is very rare. Further, polypoid
      type of esophageal cancer is also rare. We have recently treated a case of
      basaloid squamous cell carcinoma which presented as a 1.3-cm esophageal polyp. A
      48-year-old woman was referred to our hospital because of a polypoid mass at 36
      cm distance from the upper incisor on endoscopic examination, and the result of
      the biopsy was basaloid squamous cell carcinoma. The patient underwent Ivor Lewis
      operation with lymph node dissection. Two basaloid squamous cell carcinomas, of
      1.3 and 0.4 cm, were diagnosed in the final pathologic examination. Regular
      periodic follow-up showed no evidence of recurrence or metastasis in the 5-month
      postoperative period.

PMID- 29033780
TI  - Evolutionary Musicology Meets Embodied Cognition: Biocultural Coevolution and the
      Enactive Origins of Human Musicality.
AB  - Despite evolutionary musicology's interdisciplinary nature, and the diverse
      methods it employs, the field has nevertheless tended to divide into two main
      positions. Some argue that music should be understood as a naturally selected
      adaptation, while others claim that music is a product of culture with little or
      no relevance for the survival of the species. We review these arguments,
      suggesting that while interesting and well-reasoned positions have been offered
      on both sides of the debate, the nature-or-culture (or adaptation vs. non
      adaptation) assumptions that have traditionally driven the discussion have
      resulted in a problematic either/or dichotomy. We then consider an alternative
      "biocultural" proposal that appears to offer a way forward. As we discuss, this
      approach draws on a range of research in theoretical biology, archeology,
      neuroscience, embodied and ecological cognition, and dynamical systems theory
      (DST), positing a more integrated model that sees biological and cultural
      dimensions as aspects of the same evolving system. Following this, we outline the
      enactive approach to cognition, discussing the ways it aligns with the
      biocultural perspective. Put simply, the enactive approach posits a deep
      continuity between mind and life, where cognitive processes are explored in terms
      of how self-organizing living systems enact relationships with the environment
      that are relevant to their survival and well-being. It highlights the embodied
      and ecologically situated nature of living agents, as well as the active role
      they play in their own developmental processes. Importantly, the enactive
      approach sees cognitive and evolutionary processes as driven by a range of
      interacting factors, including the socio-cultural forms of activity that
      characterize the lives of more complex creatures such as ourselves. We offer some
      suggestions for how this approach might enhance and extend the biocultural model.
      To conclude we briefly consider the implications of this approach for practical
      areas such as music education.

PMID- 29033781
TI  - Direct Neuronal Reprogramming for Disease Modeling Studies Using Patient-Derived
      Neurons: What Have We Learned?
AB  - Direct neuronal reprogramming, by which a neuron is formed via direct conversion
      from a somatic cell without going through a pluripotent intermediate stage,
      allows for the possibility of generating patient-derived neurons. A unique
      feature of these so-called induced neurons (iNs) is the potential to maintain
      aging and epigenetic signatures of the donor, which is critical given that many
      diseases of the CNS are age related. Here, we review the published literature on
      the work that has been undertaken using iNs to model human brain disorders.
      Furthermore, as disease-modeling studies using this direct neuronal reprogramming
      approach are becoming more widely adopted, it is important to assess the criteria
      that are used to characterize the iNs, especially in relation to the extent to
      which they are mature adult neurons. In particular: i) what constitutes an iN
      cell, ii) which stages of conversion offer the earliest/optimal time to assess
      features that are specific to neurons and/or a disorder and iii) whether
      generating subtype-specific iNs is critical to the disease-related features that
      iNs express. Finally, we discuss the range of potential biomedical applications
      that can be explored using patient-specific models of neurological disorders with
      iNs, and the challenges that will need to be overcome in order to realize these
      applications.

PMID- 29033782
TI  - Neural Correlates of Direct Access Trading in a Real Stock Market: An fMRI
      Investigation.
AB  - Background: While financial decision making has been barely explored, no study
      has previously investigated the neural correlates of individual decisions made by
      professional traders involved in real stock market negotiations, using their own
      financial resources. Aim: We sought to detect how different brain areas are
      modulated by factors like age, expertise, psychological profile (speculative risk
      seeking or aversion) and, eventually, size and type (Buy/Sell) of stock
      negotiations, made through Direct Access Trading (DAT) platforms. Subjects and
      methods: Twenty male traders underwent fMRI while negotiating in the Italian
      stock market using their own preferred trading platform. Results: At least 20
      decision events were collected during each fMRI session. Risk averse traders
      performed a lower number of financial transactions with respect to risk seekers,
      with a lower average economic value, but with a higher rate of filled proposals.
      Activations were observed in cortical and subcortical areas traditionally
      involved in decision processes, including the ventrolateral and dorsolateral
      prefrontal cortex (vlPFC, dlPFC), the posterior parietal cortex (PPC), the
      nucleus accumbens (NAcc), and dorsal striatum. Regression analysis indicated an
      important role of age in modulating activation of left NAcc, while traders'
      expertise was negatively related to activation of vlPFC. High value transactions
      were associated with a stronger activation of the right PPC when subjects' buy
      rather than sell. The success of the trading activity, based on a large number of
      filled transactions, was related with higher activation of vlPFC and dlPFC.
      Independent of chronological and professional age, traders differed in their
      attitude to DAT, with distinct brain activity profiles being detectable during
      fMRI sessions. Those subjects who described themselves as very self-confident,
      showed a lower or absent activation of both the caudate nucleus and the dlPFC,
      while more reflexive traders showed greater activation of areas involved in
      strategic decision making. Discussion: The neural correlates in DAT are similar
      to those observed in other decision making contexts. Trading is handled as a well
      learned automatic behavior by expert traders; for those who mostly rely on
      heuristics, cognitive effort decreases, and transaction speed increases, but
      decision efficiency lowers following a poor involvement of the dlPFC.

PMID- 29033783
TI  - The Mechanisms of Psychedelic Visionary Experiences: Hypotheses from Evolutionary
      Psychology.
AB  - Neuropharmacological effects of psychedelics have profound cognitive, emotional,
      and social effects that inspired the development of cultures and religions
      worldwide. Findings that psychedelics objectively and reliably produce mystical
      experiences press the question of the neuropharmacological mechanisms by which
      these highly significant experiences are produced by exogenous neurotransmitter
      analogs. Humans have a long evolutionary relationship with psychedelics, a
      consequence of psychedelics' selective effects for human cognitive abilities,
      exemplified in the information rich visionary experiences. Objective evidence
      that psychedelics produce classic mystical experiences, coupled with the finding
      that hallucinatory experiences can be induced by many non-drug mechanisms,
      illustrates the need for a common model of visionary effects. Several models
      implicate disturbances of normal regulatory processes in the brain as the
      underlying mechanisms responsible for the similarities of visionary experiences
      produced by psychedelic and other methods for altering consciousness.
      Similarities in psychedelic-induced visionary experiences and those produced by
      practices such as meditation and hypnosis and pathological conditions such as
      epilepsy indicate the need for a general model explaining visionary experiences.
      Common mechanisms underlying diverse alterations of consciousness involve the
      disruption of normal functions of the prefrontal cortex and default mode network
      (DMN). This interruption of ordinary control mechanisms allows for the release of
      thalamic and other lower brain discharges that stimulate a visual information
      representation system and release the effects of innate cognitive functions and
      operators. Converging forms of evidence support the hypothesis that the source of
      psychedelic experiences involves the emergence of these innate cognitive
      processes of lower brain systems, with visionary experiences resulting from the
      activation of innate processes based in the mirror neuron system (MNS).

PMID- 29033785
TI  - Versatile Roles of the Chromatin Remodeler CHD7 during Brain Development and
      Disease.
AB  - CHD7 (Chromo-Helicase-DNA binding protein 7) protein is an ATP-dependent
      chromatin remodeler. Heterozygous mutation of the CHD7 gene causes a severe
      congenital disease known as CHARGE syndrome. Most CHARGE syndrome patients have
      brain structural anomalies, implicating an important role of CHD7 during brain
      development. In this review, we summarize studies dissecting developmental
      functions of CHD7 in the brain and discuss pathogenic mechanisms behind
      neurodevelopmental defects caused by mutation of CHD7. As we discussed, CHD7
      protein exhibits a remarkably specific and dynamic expression pattern in the
      brain. Studies in human and animal models have revealed that CHD7 is involved in
      multiple developmental lineages and processes in the brain. Mechanistically, CHD7
      is essential for neural differentiation due to its transcriptional regulation in
      progenitor cells.

PMID- 29033787
TI  - A Novel Ex Vivo Model to Investigate the Underlying Mechanisms in Alzheimer's
      Disease.
AB  - Currently there is no widely accepted animal model reproducing the full
      pathological profile of Alzheimer's disease (AD), since the basic mechanisms of
      neurodegeneration are still poorly understood. We have proposed that the
      interaction between the alpha7 nicotinic acetylcholine receptor (alpha7-nAChR)
      and a recently discovered toxic peptide, cleaved from the acetylcholinesterase
      (AChE) C-terminus, could account for the aberrant processes occurring in AD. In
      this article we describe a new application on ex vivo model procedure, which
      combines the advantages of both in vivo and in vitro preparations, to study the
      effects of the AChE-derived peptide on the rat basal forebrain (BF). Western blot
      analysis showed that the levels of alpha7-nAChR, p-Tau and Abeta are
      differentially expressed upon the AChE-peptide administration, in a selective
      site-dependent manner. In conclusion, this methodology demonstrates the action of
      a novel peptide in triggering an AD-like phenotype and proposes a new ex vivo
      approach for manipulating and monitoring neurochemical processes contributing to
      neurodegeneration, in a time-dependent and site-specific manner.

PMID- 29033786
TI  - Wnt5a Promotes Cortical Neuron Survival by Inhibiting Cell-Cycle Activation.
AB  - beta-Amyloid protein (Abeta) is thought to cause neuronal loss in Alzheimer's
      disease (AD). Abeta treatment promotes the re-activation of a mitotic cycle and
      induces rapid apoptotic death of neurons. However, the signaling pathways
      mediating cell-cycle activation during neuron apoptosis have not been determined.
      We find that Wnt5a acts as a mediator of cortical neuron survival, and Abeta42
      promotes cortical neuron apoptosis by downregulating the expression of Wnt5a.
      Cell-cycle activation is mediated by the reduced inhibitory effect of Wnt5a in
      Abeta42 treated cortical neurons. Furthermore, Wnt5a signals through the non
      canonical Wnt/Ca2+ pathway to suppress cyclin D1 expression and negatively
      regulate neuronal cell-cycle activation in a cell-autonomous manner. Together,
      aberrant downregulation of Wnt5a signaling is a crucial step during Abeta42
      induced cortical neuron apoptosis and might contribute to AD-related
      neurodegeneration.

PMID- 29033784
TI  - Top-Down Control of Visual Attention by the Prefrontal Cortex. Functional
      Specialization and Long-Range Interactions.
AB  - The ability to select information that is relevant to current behavioral goals is
      the hallmark of voluntary attention and an essential part of our cognition.
      Attention tasks are a prime example to study at the neuronal level, how task
      related information can be selectively processed in the brain while irrelevant
      information is filtered out. Whereas, numerous studies have focused on
      elucidating the mechanisms of visual attention at the single neuron and
      population level in the visual cortices, considerably less work has been devoted
      to deciphering the distinct contribution of higher-order brain areas, which are
      known to be critical for the employment of attention. Among these areas, the
      prefrontal cortex (PFC) has long been considered a source of top-down signals
      that bias selection in early visual areas in favor of the attended features.
      Here, we review recent experimental data that support the role of PFC in
      attention. We examine the existing evidence for functional specialization within
      PFC and we discuss how long-range interactions between PFC subregions and
      posterior visual areas may be implemented in the brain and contribute to the
      attentional modulation of different measures of neural activity in visual
      cortices.

PMID- 29033789
TI  - Stress and Corticosteroids Modulate Muscarinic Long Term Potentiation (mLTP) in
      the Hippocampus.
AB  - Stress influences synaptic plasticity, learning and memory in a steroid hormone
      receptor dependent manner. Based on these findings it has been proposed that
      stress could be a major risk factor for the development of cognitive decline and
      dementia. Interestingly, evidence has been provided that stress also affects
      muscarinic, i.e., acetylcholine (ACh)-mediated neurotransmission. To learn more
      about the impact of stress and steroids on synaptic plasticity, in this study, we
      investigated the effects of stress on muscarinic long term potentiation (mLTP).
      We report that multiple, unpredictable exposure to stress depresses carbachol
      (0.5 MUM)-induced mLTP, while this effect of stress is not observed in
      hippocampal slices prepared from mice exposed only to a single stressful
      procedure. Furthermore, we demonstrate that activation of distinct steroid
      hormone receptors is involved in stress-mediated alterations of mLTP. Activation
      of mineralocorticoid receptors (MR) promotes mLTP, while glucocorticoid receptor
      (GR) activity impairs mLTP. These effects of multiple unpredictable stress on
      mLTP are long-lasting since they are detected even two weeks after the last
      stressful experience. Thus, multiple unpredictable events rather than a single
      stressful experience affect mLTP in a steroid hormone receptor dependent manner,
      suggesting that chronic unpredictable stress can lead to lasting alterations in
      hippocampal cholinergic plasticity.

PMID- 29033790
TI  - Non-aggregated Abeta25-35 Upregulates Primary Astrocyte Proliferation In Vitro.
AB  - Amyloid beta (Abeta) is a peptide cleaved from amyloid precursor protein that
      contributes to the formation of senile plaques in Alzheimer's disease (AD). The
      relationship between Abeta and astrocyte proliferation in AD remains
      controversial. Despite pathological findings of increased astrocytic mitosis in
      AD brains, in vitro studies show an inhibitory effect of Abeta on astrocyte
      proliferation. In this study, we determined the effect of an active fragment of
      Abeta (Abeta25-35) on the cell cycle progression of primary rat astrocytes. We
      found that Abeta25-35 (0.3-1.0 MUg/ml) enhanced astrocyte proliferation in vitro
      in a time- and concentration-dependent manner. Increased DNA synthesis by Abeta25
      35 was observed during the S phase of the astrocyte cell cycle, as indicated by
      proliferation kinetics and bromodeoxyuridine immunocytochemical staining.
      Aggregation of Abeta25-35 abolished the upregulatory effect of Abeta on astrocyte
      proliferation. Further examination indicated that Abeta25-35 affected astrocyte
      proliferation during early or mid-G1 phase but had no effect on DNA synthesis at
      the peak of S phase. These results provide insight into the relationship between
      Abeta25-35 and astrocyte cell cycling in AD.

PMID- 29033792
TI  - Spontaneous and Evoked Activity from Murine Ventral Horn Cultures on
      Microelectrode Arrays.
AB  - Motor neurons are the site of action for several neurological disorders and
      paralytic toxins, with cell bodies located in the ventral horn (VH) of the spinal
      cord along with interneurons and support cells. Microelectrode arrays (MEAs) have
      emerged as a high content assay platform for mechanistic studies and drug
      discovery. Here, we explored the spontaneous and evoked electrical activity of VH
      cultures derived from embryonic mouse spinal cord on multi-well plates of MEAs.
      Primary VH cultures from embryonic day 15-16 mice were characterized by
      expression of choline acetyltransferase (ChAT) by immunocytochemistry. Well
      resolved, all-or-nothing spontaneous spikes with profiles consistent with
      extracellular action potentials were observed after 3 days in vitro, persisting
      with consistent firing rates until at least day in vitro 19. The majority of the
      spontaneous activity consisted of tonic firing interspersed with coordinated
      bursting across the network. After 5 days in vitro, spike activity was readily
      evoked by voltage pulses where a minimum amplitude and duration required for
      excitation was 300 mV and 100 MUs/phase, respectively. We characterized the
      sensitivity of spontaneous and evoked activity to a host of pharmacological
      agents including AP5, CNQX, strychnine, omega-agatoxin IVA, and botulinum
      neurotoxin serotype A (BoNT/A). These experiments revealed sensitivity of the
      cultured VH to both agonist and antagonist compounds in a manner consistent with
      mature tissue derived from slices. In the case of BoNT/A, we also demonstrated
      intoxication persistence over an 18-day period, followed by partial intoxication
      recovery induced by N- and P/Q-type calcium channel agonist GV-58. In total, our
      findings suggest that VH cultures on multi-well MEA plates may represent a
      moderate throughput, high content assay for performing mechanistic studies and
      for screening potential therapeutics pertaining to paralytic toxins and
      neurological disorders.

PMID- 29033791
TI  - Protein Synthesis Inhibition and Activation of the c-Jun N-Terminal Kinase Are
      Potential Contributors to Cisplatin Ototoxicity.
AB  - Cisplatin has been regarded as an effective and versatile chemotherapeutic agent
      for nearly 40 years. Though the associated dose-dependent ototoxicity is known,
      the cellular mechanisms by which cochleovestibular hair cell death occur are not
      well understood. We have previously shown that aminoglycoside ototoxicity is
      mediated in part by cytosolic protein synthesis inhibition. Despite a lack of
      molecular similarity, aminoglycosides were shown to elicit similar stress
      pathways to cisplatin. We therefore reasoned that there may be some role of
      protein synthesis inhibition in cisplatin ototoxicity. Employing a modification
      of the bioorthogonal noncanonical amino acid tagging (BONCAT) method, we
      evaluated the effects of cisplatin on cellular protein synthesis. We show that
      cisplatin inhibits cellular protein synthesis in organ of Corti explant cultures.
      Similar to what was found after gentamicin exposure, cisplatin activates both the
      c-Jun N-terminal kinase (JNK) and mammalian target of rapamycin (mTOR) pathways.
      In contrast to aminoglycosides, cisplatin also inhibits protein synthesis in all
      cochlear cell types. We further demonstrate that the multikinase inhibitor
      sorafenib completely prevents JNK activation, while providing only moderate hair
      cell protection. Simultaneous stimulation of cellular protein synthesis by
      insulin, however, significantly improved hair cell survival in culture. The
      presented data provides evidence for a potential role of protein synthesis
      inhibition in cisplatin-mediated ototoxicity.

PMID- 29033788
TI  - Zinc as a Neuromodulator in the Central Nervous System with a Focus on the
      Olfactory Bulb.
AB  - The olfactory bulb (OB) is central to the sense of smell, as it is the site of
      the first synaptic relay involved in the processing of odor information. Odor
      sensations are first transduced by olfactory sensory neurons (OSNs) before being
      transmitted, by way of the OB, to higher olfactory centers that mediate olfactory
      discrimination and perception. Zinc is a common trace element, and it is highly
      concentrated in the synaptic vesicles of subsets of glutamatergic neurons in some
      brain regions including the hippocampus and OB. In addition, zinc is contained in
      the synaptic vesicles of some glycinergic and GABAergic neurons. Thus, zinc
      released from synaptic vesicles is available to modulate synaptic transmission
      mediated by excitatory (e.g., N-methyl-D aspartate (NMDA), alpha-amino-3-hydroxy
      5-methyl-4-isoxazolepropionic acid (AMPA)) and inhibitory (e.g., gamma
      aminobutyric acid (GABA), glycine) amino acid receptors. Furthermore,
      extracellular zinc can alter the excitability of neurons through effects on a
      variety of voltage-gated ion channels. Consistent with the notion that zinc acts
      as a regulator of neuronal activity, we and others have shown zinc modulation
      (inhibition and/or potentiation) of amino acid receptors and voltage-gated ion
      channels expressed by OB neurons. This review summarizes the locations and
      release of vesicular zinc in the central nervous system (CNS), including in the
      OB. It also summarizes the effects of zinc on various amino acid receptors and
      ion channels involved in regulating synaptic transmission and neuronal
      excitability, with a special emphasis on the actions of zinc as a neuromodulator
      in the OB. An understanding of how neuroactive substances such as zinc modulate
      receptors and ion channels expressed by OB neurons will increase our
      understanding of the roles that synaptic circuits in the OB play in odor
      information processing and transmission.

PMID- 29033793
TI  - From Serotonin to Neuroplasticity: Evolvement of Theories for Major Depressive
      Disorder.
AB  - The serotonin (5-HT) hypothesis of depression has played an important role in the
      history of psychiatry, yet it has also been criticized for the delayed onset and
      inadequate efficacy of selective serotonin reuptake inhibitors (SSRIs). With
      evolvement of neuroscience, the neuroplasticity hypothesis of major depressive
      disorder (MDD) has been proposed and may provide a better framework for
      clarification the pathogenesis of MDD and antidepressant efficacy. In this
      article, we first summarized the evidence challenging the monoamine hypothesis
      and proposed that the antidepressant efficacy of SSRIs is not derived from
      elevated monoamine (5-HT, noradrenaline (NE), or dopamine (DA)) concentration or
      monoamine neurotransmission. Second, we reviewed the role of stress in the
      pathogenesis of MDD and gave a brief introduction to the neuroplasticity
      hypothesis of MDD. Third, we explored the possible mechanisms underlying the
      antidepressant efficacy of typical antidepressants in the context of
      neuroplasticity theory. Fourth, we tried to provide an explanatory framework for
      the significant difference in onset of efficacy between typical antidepressants
      and ketamine. Finally, we provided a brief summarization about this review
      article and some perspectives for future studies.

PMID- 29033794
TI  - Dihydroartemisinin Exerts Anti-Tumor Activity by Inducing Mitochondrion and
      Endoplasmic Reticulum Apoptosis and Autophagic Cell Death in Human Glioblastoma
      Cells.
AB  - Glioblastoma (GBM) is the most advanced and aggressive form of gliomas.
      Dihydroartemisinin (DHA) has been shown to exhibit anti-tumor activity in various
      cancer cells. However, the effect and molecular mechanisms underlying its anti
      tumor activity in human GBM cells remain to be elucidated. Our results proved
      that DHA treatment significantly reduced cell viability in a dose- and time
      dependent manner by CCK-8 assay. Further investigation identified that the cell
      viability was rescued by pretreatment either with Z-VAD-FMK, 3-methyladenine (3
      MA) or in combination. Moreover, DHA induced apoptosis of GBM cells through
      mitochondrial membrane depolarization, release of cytochrome c and activation of
      caspases-9. Enhanced expression of GRP78, CHOP and eIF2alpha and activation of
      caspase 12 were additionally confirmed that endoplasmic reticulum (ER) stress
      pathway of apoptosis was involved in the cytotoxicity of DHA. DHA-treated GBM
      cells exhibited the morphological and biochemical changes typical of autophagy.
      Co-treatment with chloroquine (CQ) significantly induced the above effects.
      Furthermore, ER stress and mitochondrial dysfunction were involved in the DHA
      induced autophagy. Further study revealed that accumulation of reactive oxygen
      species (ROS) was attributed to the DHA induction of apoptosis and autophagy. The
      illustration of these molecular mechanisms will present a novel insight for the
      treatment of human GBM.

PMID- 29033795
TI  - Cellular Mechanisms of Cortisol-Induced Changes in Mauthner-Cell Excitability in
      the Startle Circuit of Goldfish.
AB  - Predator pressure and olfactory cues (alarm substance) have been shown to
      modulate Mauthner cell (M-cell) initiated startle escape responses (C-starts) in
      teleost fish. The regulation of such adaptive responses to potential threats is
      thought to involve the release of steroid hormones such as cortisol. However, the
      mechanism by which cortisol may regulate M-cell excitability is not known. Here,
      we used intrasomatic, in vivo recordings to elucidate the acute effects of
      cortisol on M-cell membrane properties and sound evoked post-synaptic potentials
      (PSPs). Cortisol tonically decreased threshold current in the M-cell within 10
      min before trending towards baseline excitability over an hour later, which may
      indicate the involvement of non-genomic mechanisms. Consistently, current ramp
      injection experiments showed that cortisol increased M-cell input resistance in
      the depolarizing membrane, i.e., by a voltage-dependent postsynaptic mechanism.
      Cortisol also increases the magnitude of sound-evoked M-cell PSPs by reducing the
      efficacy of local feedforward inhibition (FFI). Interestingly, another pre
      synaptic inhibitory network mediating prepulse inhibition (PPI) remained
      unaffected. Together, our results suggest that cortisol rapidly increases M-cell
      excitability via a post-synaptic effector mechanism, likely a chloride
      conductance, which, in combination with its dampening effect on FFI, will
      modulate information processing to reach threshold. Given the central role of the
      M-cell in initiating startle, these results are consistent with a role of
      cortisol in mediating the expression of a vital behavior.

PMID- 29033796
TI  - Laminar and Cellular Distribution of Monoamine Receptors in Rat Medial Prefrontal
      Cortex.
AB  - The prefrontal cortex (PFC) is deeply involved in higher brain functions, many of
      which are altered in psychiatric conditions. The PFC exerts a top-down control of
      most cortical and subcortical areas through descending pathways and is densely
      innervated by axons emerging from the brainstem monoamine cell groups, namely,
      the dorsal and median raphe nuclei (DR and MnR, respectively), the ventral
      tegmental area and the locus coeruleus (LC). In turn, the activity of these cell
      groups is tightly controlled by afferent pathways arising from layer V PFC
      pyramidal neurons. The reciprocal connectivity between PFC and monoamine cell
      groups is of interest to study the pathophysiology and treatment of severe
      psychiatric disorders, such as major depression and schizophrenia, inasmuch as
      antidepressant and antipsychotic drugs target monoamine receptors/transporters
      expressed in these areas. Here we review previous reports examining the presence
      of monoamine receptors in pyramidal and GABAergic neurons of the PFC using double
      in situ hybridization. Additionally, we present new data on the quantitative
      layer distribution (layers I, II-III, V, and VI) of monoamine receptor-expressing
      cells in the cingulate (Cg), prelimbic (PrL) and infralimbic (IL) subfields of
      the medial PFC (mPFC). The receptors examined include serotonin 5-HT1A, 5-HT2A, 5
      HT2C, and 5-HT3, dopamine D1 and D2 receptors, and alpha1A-, alpha1B-, and
      alpha1D-adrenoceptors. With the exception of 5-HT3 receptors, selectively
      expressed by layers I-III GABA interneurons, the rest of monoamine receptors are
      widely expressed by pyramidal and GABAergic neurons in intermediate and deep
      layers of mPFC (5-HT2C receptors are also expressed in layer I). This complex
      distribution suggests that monoamines may modulate the communications between PFC
      and cortical/subcortical areas through the activation of receptors expressed by
      neurons in intermediate (e.g., 5-HT1A, 5-HT2A, alpha1D-adrenoceptors, dopamine D1
      receptors) and deep layers (e.g., 5-HT1A, 5-HT2A, alpha1A-adrenoceptors, dopamine
      D2 receptors), respectively. Overall, these data provide a detailed framework to
      better understand the role of monoamines in the processing of cognitive and
      emotional signals by the PFC. Likewise, they may be helpful to characterize brain
      circuits relevant for the therapeutic action of antidepressant and antipsychotic
      drugs and to improve their therapeutic action, overcoming the limitations of
      current drugs.

PMID- 29033797
TI  - White Matter Abnormalities in Children with HIV Infection and Exposure.
AB  - Background: Due to changes in guidelines and access to treatment, more children
      start combination antiretroviral therapy (ART) in infancy. With few studies
      examining the long-term effects of perinatal HIV infection and early ART on
      neurodevelopment, much is still unknown about brain maturation in the presence of
      HIV and ART. Follow-up studies of HIV infected (HIV+) children are important for
      monitoring brain development in the presence of HIV infection and ART. Methods:
      We use diffusion tensor imaging (DTI) to examine white matter (WM) in 65 HIV+ and
      46 control (HIV exposed uninfected (HEU) and HIV unexposed uninfected (HU)) 7
      year-old children. This is a follow up of a cohort studied at 5 years, where we
      previously reported lower fractional anisotropy (FA) in corticospinal tract (CST)
      and mean diffusivity (MD) increases in inferior/superior longitudinal fasciculi
      (ILF/SLF), inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus
      (UF) in HIV+ children compared to uninfected controls. In addition, we also found
      a difference in FA related to age at which ART was initiated. Results: At 7
      years, we found two regions in the left IFOF and left ILF with lower FA in HIV+
      children compared to controls. Higher MD was observed in a similar region in the
      IFOF, albeit bilaterally, as well as multiple clusters bilaterally in the
      superior corona radiata (SCR), the anterior thalamic radiation (ATR) and the
      right forceps minor. Unlike at 5 years, we found no impact on WM of ART
      initiation. In HEU children, we found a cluster in the right posterior corona
      radiata with higher FA compared to HU children, while bilateral regions in the
      CST demonstrated reduced MD. Conclusions: At age 7, despite early ART and viral
      load (VL) suppression, we continue to observe differences in WM integrity. WM
      damage observed at age 5 years persists, and new damage is evident. The continued
      observation of regions with lower FA and higher MD in HIV+ children point to
      disruptions in ongoing white matter development regardless of early ART. Lastly,
      in HEU children we find higher FA and lower MD in clusters in the CST tract
      suggesting that perinatal HIV/ART exposure has a long-term impact on WM
      development.

PMID- 29033798
TI  - Self-Regulatory Capacities Are Depleted in a Domain-Specific Manner.
AB  - Performing an act of self-regulation such as making decisions has been suggested
      to deplete a common limited resource, which impairs all subsequent self
      regulatory actions (ego depletion theory). It has however remained unclear
      whether self-referred decisions truly impair behavioral control even in seemingly
      unrelated cognitive domains, and which neurophysiological mechanisms are affected
      by these potential depletion effects. In the current study, we therefore used an
      inter-individual design to compare two kinds of depletion, namely a self-referred
      choice-based depletion and a categorization-based switching depletion, to a non
      depleted control group. We used a backward inhibition (BI) paradigm to assess the
      effects of depletion on task switching and associated inhibition processes. It
      was combined with EEG and source localization techniques to assess both
      behavioral and neurophysiological depletion effects. The results challenge the
      ego depletion theory in its current form: Opposing the theory's prediction of a
      general limited resource, which should have yielded comparable effects in both
      depletion groups, or maybe even a larger depletion in the self-referred choice
      group, there were stronger performance impairments following a task domain
      specific depletion (i.e., the switching-based depletion) than following a
      depletion based on self-referred choices. This suggests at least partly separate
      and independent resources for various cognitive control processes rather than
      just one joint resource for all self-regulation activities. The implications are
      crucial to consider for people making frequent far-reaching decisions e.g., in
      law or economy.

PMID- 29033799
TI  - A Critical Assessment of Directed Connectivity Estimates with Artificially
      Imposed Causality in the Supramammillary-Septo-Hippocampal Circuit.
AB  - Algorithms for estimating directed connectivity have become indispensable to
      further understand the neurodynamics between functionally coupled brain areas.
      The evaluation of directed connectivity on the propagation of brain activity has
      largely been based on simulated data or toy models, where various hidden
      properties of neurophysiological data may not be fully recapitulated. In this
      study, directionality was unequivocally manipulated in the freely moving rat in a
      unique dataset, where normal oscillatory interactions between the supramammillary
      nucleus (SuM) and hippocampus (HPC) were attenuated by temporary medial septal
      (MS) inactivation, and replaced by electrical stimulation of the fornix to
      evaluate the performance of several directed connectivity assessment methods. The
      directed transfer function, partial directed coherence, directed coherence, pair
      wise Geweke-Granger causality, phase slope index, and phase transfer entropy, all
      found SuM to HPC theta propagation when the MS is inactivated, and HPC activity
      was driven by peaks of simultaneously recorded SuM theta. As expected from
      theoretical expectations and simulated data, signal features including coupling
      strength, signal-to-noise ratio, and stationarity all weakly affected directed
      connectivity measures. We conclude that all the examined directed connectivity
      estimates correctly identify artificially imposed uni-directionality of brain
      oscillations in freely moving animals. Non-auto-regressive modeling based methods
      appear to be the most robust, and are least affected by inherent features in data
      such as signal-to-noise ratio and stationarity.

PMID- 29033800
TI  - Stimulation of Cortico-Subthalamic Projections Amplifies Resting Motor Circuit
      Activity and Leads to Increased Locomotion in Dopamine-Depleted Mice.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor
      function in patients with Parkinson's disease (PD). STN-DBS enables similar
      improved motor function, including increased movement speed (reduced
      bradykinesia), in the 6-OHDA dopamine-depletion mouse model of PD. Previous
      analyses of electrophysiological recordings from STN and motor cortex (M1) have
      explored signaling changes that correspond to PD and amelioration of PD symptoms.
      The most common results show an increase in beta frequency power during 'off'
      states and a reduction in beta during 'on' states. Surprisingly, however, few
      studies have analyzed whole signal measures of amplitude and coherence during
      stimulation in freely moving subjects. In previous work by the author, specific
      transfection of layer five motor cortex projections to the STN revealed an axonal
      network with collaterals reaching to multiple non-dopaminergic subcortical areas
      of the brain. The large excitatory shift that stimulation of this axonal network
      could potentially induce inspired the current study's hypothesis that
      amplification of excitatory signaling occurs during stimulation of cortico
      subthalamic projections. The results show that, in awake mice, (1) the root-mean
      square amplitudes of STN and M1 local field potentials (LFPs) are significantly
      decreased ipsilateral to chronic unilateral 6-OHDA lesions, (2) stimulation of
      cortico-subthalamic projections increases the amplitude of M1- and STN-LFPs, and
      3) M1-LFP amplitude correlates strongly with locomotion speed in lesioned mice.
      Together, these findings demonstrate that bradykinesia-reducing stimulation of
      cortico-subthalamic projections amplifies both cortical and subcortical motor
      circuit activity in unilaterally dopamine-depleted mice. Most PD treatments are
      focused on increasing dopamine in the dorsal striatum. However, in this study,
      stimulation of layer five cortico-subthalamic glutamatergic axons that do not
      directly project to dopaminergic neurons increased movement and amplified cortico
      subthalamic excitatory signaling in dopamine-depleted mice. The correlation
      between M1-LFP amplitude and locomotion speed observed in these mice points to a
      role for upregulated hyperdirect pathway excitatory signaling in bradykinesia
      amelioration. In addition to providing insight into the elusive mechanisms of
      DBS, these motor circuit amplification relationships suggest that specific
      manipulation of NMDA, AMPA, and/or metabotropic glutamate receptors in the
      hyperdirect pathway may be beneficial for upregulating signaling and movement in
      PD.

PMID- 29033801
TI  - Heavy Drinking in College Students Is Associated with Accelerated Gray Matter
      Volumetric Decline over a 2 Year Period.
AB  - Background: Heavy and/or harmful alcohol use while in college is a perennial and
      significant public health issue. Despite the plethora of cross-sectional research
      suggesting deleterious effects of alcohol on the brain, there is a lack of
      literature investigating the longitudinal effects of alcohol consumption on the
      adolescent brain. We aim to probe the longitudinal effects of college drinking on
      gray matter change in students during this crucial neurodevelopmental period.
      Methods: Data were derived from the longitudinal Brain and Alcohol Research in
      College Students (BARCS) study of whom a subset underwent brain MRI scans at two
      time points 24 months apart. Students were young adults with a mean age at
      baseline of about 18.5 years. Based on drinking metrics assessed at both baseline
      and followup, subjects were classified as sustained abstainers/light drinkers (N
      = 45) or sustained heavy drinkers (N = 84) based on criteria established in prior
      literature. Gray matter volumetric change (GMV-c) maps were derived using the
      longitudinal DARTEL pipeline as implemented in SPM12. GMV-c maps were then
      subjected to a 1-sample and 2-sample t-test in SPM12 to determine within- and
      between-group GMV-c differences in drinking groups. Supplementary between-group
      differences were also computed at baseline only. Results: Within-group analysis
      revealed significant decline in GMV in both groups across the 2 year followup
      period. However, tissue loss in the sustained heavy drinking group was more
      significant, larger per region, and more widespread across regions compared to
      abstainers/light drinkers. Between-group analysis confirmed the above and showed
      a greater rate of GMV-c in the heavy drinking group in several brain regions
      encompassing inferior/medial frontal gyrus, parahippocampus, and anterior
      cingulate. Supplementary analyses suggest that some of the frontal differences
      existed at baseline and progressively worsened. Conclusion: Sustained heavy
      drinking while in college was associated with accelerated GMV decline in brain
      regions involved with executive functioning, emotional regulation, and memory,
      which are critical to everyday life functioning. Areas of significant GMV
      decreases also overlapped largely with brain reward and stress systems implicated
      in addictive behavior.

PMID- 29033802
TI  - The Neurobiological Mechanism of Chemical Aversion (Emetic) Therapy for Alcohol
      Use Disorder: An fMRI Study.
AB  - A recent NIH epidemiology study found the lifetime prevalence of alcohol use
      disorder in the United States to be 29%. Alcohol drinking behavior is strongly
      "learned" via pleasure center activation/reinforcement. Alcohol craving is a
      powerful desire to drink alcoholic beverages. Craving was added as one of the
      defining criteria for alcohol use disorder in DSM5, and craving reduction is
      becoming an increasingly important treatment goal. In the current study, patients
      with alcohol use disorder received 10 days of inpatient multi-modal treatments at
      Schick Shadel Hospital (SSH) of Seattle. The treatments included five chemical
      aversion conditioning sessions that associated alcohol cues (and alcohol) with
      nausea and emesis. All patients met DSM4 criteria for alcohol use disorder, were
      heavy drinkers, and reported craving alcohol pre-treatment. Craving reduction was
      one of the primary treatment goals. This is the first fMRI study to measure the
      effects of chemical aversion therapy on alcohol craving-related brain activity.
      Patients were recruited as subjects for the University of Washington (UW) brain
      scan study following SSH admission but before treatment onset. Prior to
      treatment, patients reported craving/desire for alcohol. After treatment (after
      four SSH chemical aversion treatments, again after five SSH chemical treatments,
      30 and 90-days post-discharge), these same patients reported avoidance/aversion
      to alcohol. Most of the participants (69%) reported being still sober 12 months
      post-treatment. Consistent with a craving reduction mechanism of how chemical
      aversion therapy facilitates sobriety, results of the UW fMRI brain scans showed
      significant pre- to post-treatment reductions in craving-related brain activity
      in the occipital cortex. Additional fMRI brain scan studies are needed to further
      explore the neurobiological mechanism of chemical aversion therapy treatment for
      alcohol use disorder, and other substance use disorders for which chemical
      aversion therapy is used (e.g., opioid dependence and cocaine dependence).
      Substance use disorders are estimated to affect well over one billion people
      worldwide.

PMID- 29033803
TI  - Moderate Maternal Alcohol Exposure on Gestational Day 12 Impacts Anxiety-Like
      Behavior in Offspring.
AB  - Among the numerous consequences of prenatal alcohol exposure (PAE) is an increase
      in anxiety-like behavior that can prove debilitating to daily functioning. A
      significant body of literature has linked gestational day 12 (G12) heavy ethanol
      exposure with social anxiety, evident in adolescent males and females. However,
      the association between non-social anxiety-like behavior and moderate alcohol
      exposure, a more common pattern of drinking in pregnant women, is yet
      unidentified. To model moderate PAE (mPAE), we exposed pregnant Sprague-Dawley
      rats to either room air or vaporized ethanol for 6 h on G12. Adolescent offspring
      were then tested on postnatal days (P) 41-47 in one of the following four anxiety
      assays: novelty-induced hypophagia (NIH), elevated plus maze (EPM), light-dark
      box (LDB) and open-field (OF). Our findings revealed significant increases in
      measures of anxiety-like behavior in male PAE offspring in the NIH, LDB and OF,
      with no differences observed in females on any test. Additionally, male offspring
      who demonstrated heightened anxiety-like behavior as adolescents demonstrated
      decreased anxiety-like behavior in adulthood, as measured by a marble-burying
      test (MBT), while females continued to be unaffected in adulthood. These results
      suggest that mPAE leads to dynamic changes in anxiety-like behavior exclusively
      in male offspring.

PMID- 29033804
TI  - Second Language Word Learning through Repetition and Imitation: Functional
      Networks as a Function of Learning Phase and Language Distance.
AB  - Introduction and Aim: Repetition and imitation are among the oldest second
      language (L2) teaching approaches and are frequently used in the context of L2
      learning and language therapy, despite some heavy criticism. Current neuroimaging
      techniques allow the neural mechanisms underlying repetition and imitation to be
      examined. This fMRI study examines the influence of verbal repetition and
      imitation on network configuration. Integration changes within and between the
      cognitive control and language networks were studied, in a pair of linguistically
      close languages (Spanish and French), and compared to our previous work on a
      distant language pair (Ghazi-Saidi et al., 2013). Methods: Twelve healthy native
      Spanish-speaking (L1) adults, and 12 healthy native Persian-speaking adults
      learned 130 new French (L2) words, through a computerized audiovisual repetition
      and imitation program. The program presented colored photos of objects.
      Participants were instructed to look at each photo and pronounce its name as
      closely as possible to the native template (imitate). Repetition was encouraged
      as many times as necessary to learn the object's name; phonological cues were
      provided if necessary. Participants practiced for 15 min, over 30 days, and were
      tested while naming the same items during fMRI scanning, at week 1 (shallow
      learning phase) and week 4 (consolidation phase) of training. To compare this set
      of data with our previous work on Persian speakers, a similar data analysis plan
      including accuracy rates (AR), response times (RT), and functional integration
      values for the language and cognitive control network at each measure point was
      included, with further L1-L2 direct comparisons across the two populations.
      Results and Discussion: The evidence shows that learning L2 words through
      repetition induces neuroplasticity at the network level. Specifically, L2 word
      learners showed increased network integration after 3 weeks of training, with
      both close and distant language pairs. Moreover, higher network integration was
      observed in the learners with the close language pair, suggesting that repetition
      effects on network configuration vary as a function of task complexity.

PMID- 29033805
TI  - Musical Expertise Increases Top-Down Modulation Over Hippocampal Activation
      during Familiarity Decisions.
AB  - The hippocampus has classically been associated with episodic memory, but is
      sometimes also recruited during semantic memory tasks, especially for the skilled
      exploration of familiar information. Cognitive control mechanisms guiding
      semantic memory search may benefit from the set of cognitive processes at stake
      during musical training. Here, we examined using functional magnetic resonance
      imaging, whether musical expertise would promote the top-down control of the left
      inferior frontal gyrus (LIFG) over the generation of hippocampally based goal
      directed thoughts mediating the familiarity judgment of proverbs and musical
      items. Analyses of behavioral data confirmed that musical experts more
      efficiently access familiar melodies than non-musicians although such increased
      ability did not transfer to verbal semantic memory. At the brain level, musical
      expertise specifically enhanced the recruitment of the hippocampus during
      semantic access to melodies, but not proverbs. Additionally, hippocampal
      activation contributed to speed of access to familiar melodies, but only in
      musicians. Critically, causal modeling of neural dynamics between LIFG and the
      hippocampus further showed that top-down excitatory regulation over the
      hippocampus during familiarity decision specifically increases with musical
      expertise - an effect that generalized across melodies and proverbs. At the local
      level, our data show that musical expertise modulates the online recruitment of
      hippocampal response to serve semantic memory retrieval of familiar melodies. The
      reconfiguration of memory network dynamics following musical training could
      constitute a promising framework to understand its ability to preserve brain
      functions.

PMID- 29033806
TI  - Is Congenital Amusia a Disconnection Syndrome? A Study Combining Tract- and
      Network-Based Analysis.
AB  - Previous studies on congenital amusia mainly focused on the impaired fronto
      temporal pathway. It is possible that neural pathways of amusia patients on a
      larger scale are affected. In this study, we investigated changes in structural
      connections by applying both tract-based and network-based analysis to DTI data
      of 12 subjects with congenital amusia and 20 demographic-matched normal controls.
      TBSS (tract-based spatial statistics) was used to detect microstructural changes.
      The results showed that amusics had higher diffusivity indices in the corpus
      callosum, the right inferior/superior longitudinal fasciculus, and the right
      inferior frontal-occipital fasciculus (IFOF). The axial diffusivity values of the
      right IFOF were negatively correlated with musical scores in the amusia group.
      Network-based analysis showed that the efficiency of the brain network was
      reduced in amusics. The impairments of WM tracts were also found to be correlated
      with reduced network efficiency in amusics. This suggests that impaired WM tracts
      may lead to the reduced network efficiency seen in amusics. Our findings suggest
      that congenital amusia is a disconnection syndrome.

PMID- 29033807
TI  - Walking through Architectural Spaces: The Impact of Interior Forms on Human Brain
      Dynamics.
AB  - Neuroarchitecture uses neuroscientific tools to better understand architectural
      design and its impact on human perception and subjective experience. The form or
      shape of the built environment is fundamental to architectural design, but not
      many studies have shown the impact of different forms on the inhabitants'
      emotions. This study investigated the neurophysiological correlates of different
      interior forms on the perceivers' affective state and the accompanying brain
      activity. To understand the impact of naturalistic three-dimensional (3D)
      architectural forms, it is essential to perceive forms from different
      perspectives. We computed clusters of form features extracted from pictures of
      residential interiors and constructed exemplary 3D room models based on and
      representing different formal clusters. To investigate human brain activity
      during 3D perception of architectural spaces, we used a mobile brain/body imaging
      (MoBI) approach recording the electroencephalogram (EEG) of participants while
      they naturally walk through different interior forms in virtual reality (VR). The
      results revealed a strong impact of curvature geometries on activity in the
      anterior cingulate cortex (ACC). Theta band activity in ACC correlated with
      specific feature types (rs (14) = 0.525, p = 0.037) and geometry (rs (14) = 
      0.579, p = 0.019), providing evidence for a role of this structure in processing
      architectural features beyond their emotional impact. The posterior cingulate
      cortex and the occipital lobe were involved in the perception of different room
      perspectives during the stroll through the rooms. This study sheds new light on
      the use of mobile EEG and VR in architectural studies and provides the
      opportunity to study human brain dynamics in participants that actively explore
      and realistically experience architectural spaces.

PMID- 29033809
TI  - Characterizing Neural Entrainment to Hierarchical Linguistic Units using
      Electroencephalography (EEG).
AB  - To understand speech, listeners have to combine the words they hear into phrases
      and sentences. Recent magnetoencephalography (MEG) and electrocorticography
      (ECoG) studies show that cortical activity is concurrently entrained/synchronized
      to the rhythms of multiple levels of linguistic units including words, phrases,
      and sentences. Here we investigate whether this phenomenon can be observed using
      electroencephalography (EEG), a technique that is more widely available than MEG
      and ECoG. We show that the EEG responses concurrently track the rhythms of
      hierarchical linguistic units such as syllables/words, phrases, and sentences.
      The strength of the sentential-rate response correlates with how well each
      subject can detect random words embedded in a sequence of sentences. In contrast,
      only a syllabic-rate response is observed for an unintelligible control stimulus.
      In sum, EEG provides a useful tool to characterize neural encoding of
      hierarchical linguistic units, potentially even in individual participants.

PMID- 29033808
TI  - Size Aftereffects Are Eliminated When Adaptor Stimuli Are Prevented from Reaching
      Awareness by Continuous Flash Suppression.
AB  - Size aftereffects are a compelling perceptual phenomenon in which we perceive the
      size of a stimulus as being different than it actually is following a period of
      visual stimulation of an adapter stimulus with a different size. Here, we used
      continuous flash suppression (CFS) to determine if size aftereffects require a
      high-level appraisal of the adapter stimulus. The strength of size aftereffects
      was quantified following a 3-s exposure to perceptually visible and invisible
      adapters. Participants judged the size of a target that followed the adapter in
      comparison to a subsequent reference. Our experiments demonstrate that the
      adapter no longer influenced the perceived size of the subsequent target stimulus
      under CFS. We conclude that the perception of size aftereffects is prevented when
      CFS is used to suppress the conscious awarness of the adapting stimulus.

PMID- 29033810
TI  - Cooperation and Competition with Hyperscanning Methods: Review and Future
      Application to Emotion Domain.
AB  - Cooperation and competition, as two common and opposite examples of interpersonal
      dynamics, are thought to be reflected by different cognitive, neural, and
      behavioral patterns. According to the conventional approach, they have been
      explored by measuring subjects' reactions during individual performance or turn
      based interactions in artificial settings, that don't allow on-line, ecological
      enactment of real-life social exchange. Considering the importance of these
      factors, and accounting for the complexity of such phenomena, the hyperscanning
      approach emerged as a multi-subject paradigm since it allows the simultaneous
      recording of the brain activity from multiple participants interacting. In this
      view, the present paper aimed at reviewing the most significant work about
      cooperation and competition by EEG hyperscanning technique, which proved to be a
      promising tool in capturing the sudden course of social interactions. In detail,
      the review will consider and group different experimental tasks that have been
      developed so far: (1) paradigms that used rhythm, music and motor
      synchronization; (2) card tasks taken from the Game Theory; (3) computerized
      tasks; and (4) possible real-life applications. Finally, although highlighting
      the potential contribution of such approach, some important limitations about
      these paradigms will be elucidated, with a specific focus on the emotional
      domain.

PMID- 29033812
TI  - The Successful Use of a Novel Microwave Device in the Treatment of a Plantar
      Wart.
AB  - Plantar warts, caused by the human papilloma virus (HPV), are a commonly
      encountered condition presenting in clinic. In adults, an array of various
      therapies exists, frequently with modest results particularly with plantar
      lesions. Microwaves have had limited uses for medical purposes. Recently a new
      portable microwave device has been approved for the treatment of skin lesions.
      Prior research has demonstrated immuno-stimulatory effects against HPV infection.
      We report the application of a novel portable medical microwave unit to treat a
      long-standing plantar wart which had failed to respond to other treatment
      modalities.

PMID- 29033811
TI  - Altered Local Spatiotemporal Consistency of Resting-State BOLD Signals in
      Patients with Generalized Tonic-Clonic Seizures.
AB  - The purpose of this study was to evaluate the spatiotemporal Consistency of
      spontaneous activities in local brain regions in patients with generalized tonic
      clonic seizures (GTCS). The resting-state fMRI data were acquired from nineteen
      patients with GTCS and twenty-two matched healthy subjects. FOur-dimensional
      (spatiotemporal) Consistency of local neural Activities (FOCA) metric was used to
      analyze the spontaneous activity in whole brain. The FOCA difference between two
      groups were detected using a two sample t-test analysis. Correlations between the
      FOCA values and features of seizures were analyzed. The findings of this study
      showed that patients had significantly increased FOCA in motor-related cortex
      regions, including bilateral supplementary motor area, paracentral lobule,
      precentral gyrus and left basal ganglia, as well as a substantial reduction of
      FOCA in regions of default mode network (DMN) and parietal lobe. In addition,
      several brain regions in DMN demonstrated more reduction with longer duration of
      epilepsy and later onset age, and the motor-related regions showed higher FOCA
      value in accompany with later onset age. These findings implicated the
      abnormality of motor-related cortical network in GTCS which were associated with
      the genesis and propagation of epileptiform activity. And the decreased FOCA in
      DMN might reflect the intrinsic disturbance of brain activity. Moreover, our
      study supported that the FOCA might be potential tool to investigate local brain
      spontaneous activity related with the epileptic activity, and to provide
      important insights into understanding the underlying pathophysiological
      mechanisms of GTCS.

PMID- 29033813
TI  - Recurrence of Melanoma after Starting Apremilast for Psoriasis.
AB  - This is a report on a 32-year-old man with a history of two previous melanomas
      with concurrent plaque-type psoriasis. His history dates to 2009, when he was
      diagnosed with his first melanoma on the right occiput, Clark's level IV, tumor
      thickness 1.53 mm, nonulcerated, mitotic index 1/mm2. He subsequently developed
      nodal recurrence after an initial negative sentinel lymph node biopsy and was
      treated with complete lymph node dissection. In 2012, he was diagnosed with a
      second primary melanoma on the right upper chest, Clark's level IV, tumor
      thickness 0.9 mm, nonulcerated, mitotic index 3/mm2. Due to worsening
      longstanding plaque-type psoriasis in 2015 he was placed on apremilast, with a
      dramatic improvement in his psoriasis within 4 months of starting therapy.
      Shortly thereafter the patient developed multiple blue-colored skin papules on
      the scalp near his first melanoma and on the trunk and upper limbs that on biopsy
      proved to be due to cutaneous metastasis of melanoma. The patient discontinued
      the apremilast as there was a concern that his tumor had recurred because of the
      drug. Apremilast is a phosphodiesterase-4 inhibitor that impairs the innate
      immune system, which mediates cancer immunosurveillance. It is postulated that
      the use of apremilast in our patient resulted in impaired cancer
      immunosurveillance and led to a recurrence of his melanoma. Although one cannot
      exclude the possibility of coincidental recurrence of an already metastatic
      melanoma (to the lymph nodes), caution should be exercised when considering
      apremilast in the context of patients with known malignancy, in particular
      melanoma.

PMID- 29033814
TI  - A Case of Aplasia Cutis Congenita Type VI: Bart Syndrome.
AB  - Aplasia cutis congenita type VI, also known as Bart syndrome, is a rare genetic
      mechanobullous disorder characterized by congenital localized absence of skin,
      mucocutaneous blistering lesions, and nail abnormalities. We present the case of
      a 4-h-old male newborn who presented with complete absence of skin over the
      anteromedial aspect of both lower legs associated with nail dystrophy since
      birth. After a few days, he developed blisters that were consistent with
      epidermolysis bullosa in histopathological examination. There was no systemic
      involvement such as pyloric atresia, ureteral stenosis, renal abnormalities, or
      arthrogryposis. All laboratory work and imaging studies were normal. A diagnosis
      of Bart syndrome was made based on previous presentation. We managed the patient
      with conservative methods. Complete epithelialization occurred after several
      weeks.

PMID- 29033815
TI  - Cutaneous Nocardiosis Simulating Cutaneous Lymphatic Sporotrichosis.
AB  - Sporotrichosis is the subcutaneous mycosis caused by several species of the
      Sporothrix genus. With worldwide occurrence, the State of Rio de Janeiro is
      presently undergoing a zoonotic sporotrichosis epidemic. The form of
      lymphocutaneous nocardiosis is rare, being caused especially by Nocardia
      brasiliensis. It appears as a nodular or ulcerated lesion, with multiple painful
      erythematous nodules or satellite pustules distributed along the lymphatic tract,
      similar to the lymphocutaneous variant of sporotrichosis. We present a 61-year
      old man who, after an insect bite in the left leg, developed an ulcerated lesion
      associated with ascending lymphangitis, nonresponsive to previous antibiotic
      therapies. The patient was admitted for investigation, based on the main
      diagnostic hypothesis of lymphatic cutaneous sporotrichosis entailed by the
      highly suggestive morphology, associated with the epidemiologic information that
      he is a resident of the city of Rio de Janeiro. While culture results were being
      awaited, the patient was medicated with sulfamethoxazole-trimethoprim to cover CA
      MRSA and evolved with total healing of the lesions. After hospital discharge,
      using an ulcer fragment, an Actinomyces sp. was cultivated and N. brasiliensis
      was identified by molecular biology. The objective of this report is to
      demonstrate a case of lymphocutaneous nocardiosis caused by N. brasiliensis after
      a probable insect bite. Despite the patient being a resident of the State of Rio
      de Janeiro (endemic region for sporotrichosis), it is highlighted that it is
      necessary to be aware of the differential diagnoses of an ulcerated lesion with
      lymphangitis, favoring an early diagnosis and appropriate treatment of the
      illness.

PMID- 29033816
TI  - Verruciform Xanthoma of a Lower Lip Lesion: A New Case and Review of the
      Literature.
AB  - A non-smoking man in his seventh decade presented with a lesion he had had for
      about 5 years on the right external surface of the lip 1 mm from the vermilion
      border. On physical examination, a yellowish-coloured, non-tender, verrucous mass
      of 0.5 * 0.7 cm was observed. A histopathological examination of the first 3-mm
      punch biopsy was non-diagnostic. The histopathological evaluation of a second, 5
      mm-deep punch biopsy made by a pathology expert in oral lesions revealed a
      diagnosis of verruciform xanthoma. The key to the diagnosis of verruciform
      xanthoma is to recognize xanthoma cells. However, these cells may be insufficient
      in number in small and superficial biopsy material and overlooked by a
      pathologist especially when lacking knowledge of this uncommon lesion.
      Verruciform xanthoma of the lower lip at the vermilion border is an extremely
      rare entity described in 5 cases worldwide to date. We aimed to bring verruciform
      xanthoma to readers' attention for a differential diagnosis of lower lip diseases
      and to prevent overdiagnosis and overtreatment of this lesion unfamiliar to
      otorhinolaryngologists.

PMID- 29033817
TI  - Cholesterotic Fibrous Histiocytoma in a Patient with Metabolic Syndrome.
AB  - Among the many variants of dermatofibroma, dermatofibroma with cholesterol cleft
      (cholesterotic fibrous histiocytoma) is extremely rare. Here, we describe the
      case of a 50-year-old male patient with a cholesterotic fibrous histiocytoma on
      his left lower leg. He presented with a hyperkeratotic nodule 6 mm in diameter
      with a brown surface on the extensor surface of his left lower leg. The lesion
      had developed over the course of a few years without any tendency to heal. A skin
      biopsy performed on the tumor showed histopathological findings compatible with
      those of dermatofibroma. Interestingly, the lesion included many cholesterol
      clefts, as well as foamy histiocytes and multinucleated giant cells around them.
      He had had metabolic syndrome for years. To the best of our knowledge, this is
      the first report of a cholesterotic fibrous histiocytoma in a patient with
      metabolic syndrome. We conclude that the altered microenvironment caused by
      metabolic syndrome, as well as hyperlipoproteinemia itself, may play a role in
      the pathogenesis of this rare case.

PMID- 29033818
TI  - Itolizumab - A New Biologic for Management of Psoriasis and Psoriatic Arthritis.
AB  - Psoriasis is a chronic, relapsing, inflammatory, immune-mediated systemic disease
      with mainly skin and joint manifestations. The available treatment options to
      cure psoriasis include topical therapy, phototherapy, and biological therapy.
      Biological therapy has become a promising option due to the rapid action and less
      adverse effects associated with its use. The newly developed biologic itolizumab
      is a humanized recombinant anti-CD6 monoclonal antibody of IgG1 isotype that
      binds to domain 1 of CD6, thereby immunomodulating human lymphocytes without
      interfering with the binding of CD6 to the activated leukocyte-cell adhesion
      molecule. In this case series, a total of 5 patients with chronic plaque
      psoriasis were treated with itolizumab. They exhibited a rapid PASI 75 response
      after 4 doses of itolizumab infusion. The patients were poor responders to
      methotrexate and/or cyclosporine therapy for a long time. All infusions were well
      tolerated by all patients with no adverse reactions or infections during the
      treatment period. Itolizumab can be a good option for management of psoriasis and
      psoriatic arthritis.

PMID- 29033819
TI  - An Unusual Presentation of Pyoderma Gangrenosum Leading to Systemic Inflammatory
      Response Syndrome.
AB  - This is a report of an atypical presentation of pyoderma gangrenosum (PG) in a 26
      year-old male who had a negative septic screen. The patient had a life
      threatening presentation requiring an intensive care unit (ICU) admission for
      vasopressor support. It was thought that the likely cause of circulatory collapse
      was an overwhelming cytokine reaction or systemic inflammatory response syndrome
      (SIRS) secondary to extensive PG lesions rather than septic shock. The patient
      presented with multiple large ulcers, the largest being 4 cm in diameter on the
      central chest. He developed fevers and circulatory shock preceding his ICU
      admission. Microbiological specimens, including blood cultures and wound swabs,
      were negative for any growth (bacterial, fungal, and tuberculosis). No infective
      foci could be identified as a cause of hemodynamic instability. During admission,
      the patient's condition was complicated by multi-organ dysfunction. Wound
      debridement extending to the deep fascia on the anterior chest, back, bilateral
      shoulders, and right upper thigh was deemed necessary and performed by the
      plastic surgery team. Histopathology showed abundant neutrophils but could not
      confirm an infective process. Overall, the patient made an impressive recovery
      with almost complete healing of all lesions following oral prednisolone alone.
      Based on the history and clinical and laboratory findings, a diagnosis of PG
      complicated by a SIRS was favored. Very few cases of neutrophilic dermatoses have
      been described in this way. A similar presentation has been described in a 76
      year-old female with lower-leg ulcers who developed circulatory shock and
      required an amputation. Lesions continued to appear despite antibiotics and
      surgical treatment. Septic screen was negative. She was subsequently diagnosed
      with PG and recovered rapidly after steroid therapy.

PMID- 29033820
TI  - Pachyderma in Primary Cutaneous NK and T-Cell Lymphoma and Leukemia Cutis.
AB  - BACKGROUND: Pachyderma is defined as severely thickened skin with deep folds and
      is occasionally observed with primary cutaneous NK and T-cell lymphoma (pCNKTCL),
      primary cutaneous B-cell lymphoma (pCBCL), and leukemia cutis (LC). AIM: To
      describe the clinical, histological, and therapeutic particularities of a series
      of pCNKTCL, pCBCL, and LC patients with pachyderma. RESULTS: In a series of
      pCNKTCL (n = 70), pCBCL (n = 12), and LC (n = 2) patients followed up during 9
      years, 6 cases of pachyderma were observed. Pachyderma occurred on the arms (n =
      2), thighs (n = 1), forehead (n = 1), and face (n = 2). The mean age of the
      patients was 69 years (51-82). The stages were erythrodermic (T4) mycosis
      fungoides (MF) (n = 1), folliculotropic MF (FMF) (n = 2), classic (T2) MF (n =
      2), and chronic myeloid leukemia (n = 1). The erythrodermic MF patient with acute
      pachyderma on the right arm responded rapidly to oral steroids. The other cases
      were indolent, appeared progressively, and were highly treatment resistant.
      Histology revealed dense dermal neoplastic infiltration. The immunohistological
      profile of the pachydermic lesions was similar to common MF and LC. CONCLUSION:
      Pachyderma is an atypical manifestation of MF and LC and may occur on the face
      (FMF) or the extremities (MF). The rapidly appearing pachyderma may be transitory
      and responds readily to oral steroids.

PMID- 29033821
TI  - Certolizumab Pegol-Induced Folliculitis-Like Lichenoid Sarcoidosis in a Patient
      with Rheumatoid Arthritis.
AB  - Anti-tumor necrosis factor alpha (TNF-alpha) biologic agents are used for
      treating refractory sarcoidosis. However, sarcoidosis-like epithelioid cell
      granulomas may develop during anti-TNF-alpha treatment. A 63-year-old man
      suffering from rheumatoid arthritis was treated with oral methotrexate and
      methylprednisolone for 4 years. He subsequently started biweekly subcutaneous
      injections of certolizumab pegol. Three months later, light red follicular
      papules developed on his chest and they spread over the trunk and bilateral upper
      arms. Histopathology of a lesion showed a sharply demarcated noncaseating
      epithelioid cell granuloma with multi-nucleated giant cells in the upper
      perifollicular area. The follicular papules subsided following discontinuation of
      certolizumab pegol. Folliculitis-like lichenoid sarcoidosis should be included
      among the adverse cutaneous reactions of anti-TNF-alpha treatment.

PMID- 29033822
TI  - Facial Edema in an Elderly Man: An Unusual Presentation of Nonepisodic Angioedema
      with Eosinophilia.
AB  - Nonepisodic angioedema with eosinophilia (NEAE) is a rare allergic disease with a
      young Japanese and East Asian female predominance. NEAE features transient,
      nonrecurrent angioedema and peripheral blood eosinophilia without visceral organ
      involvement. Angioedema in NEAE occurs on the extremities, while the trunk and
      face are rarely involved. Here, we report a case of NEAE affecting only the face
      in an 80-year-old Japanese man. He was otherwise healthy and took no medication
      until the sudden development of angioedema on the face. The extremities and trunk
      were not involved. Skin biopsy examination revealed eosinophilic infiltration and
      degranulation between collagen bundles through the entire dermis, and
      perivascular and perifollicular infiltration of eosinophils and lymphocytes, but
      no evidence of vasculitis. Peripheral hypereosinophilia and high serum thymus-
      and activation-regulated chemokine (TARC) level were noted. Visceral organ
      involvement, parasite infection, and an allergic response were not detected in
      the patient. Administration of oral corticosteroid improved his symptoms rapidly
      and dramatically with improvements in the blood eosinophil count and serum TARC
      level. After the corticosteroid was discontinued, no recurrence was observed for
      3 years. Thus, he was diagnosed as having NEAE. It should be noted that
      angioedema with eosinophilia might occur with an unusual presentation and might
      develop in elderly patients.

PMID- 29033823
TI  - Successful Topical Treatment of Pigmented Purpuric Lichenoid Dermatitis of
      Gougerot-Blum in a Young Patient: A Case Report and Summary of the Most Common
      Pigmented Purpuric Dermatoses.
AB  - We report the case of a 12-year-old girl who presented a rash with reddish-brown
      patches on the trunk and extremities indicative of pigmented purpuric lichenoid
      dermatitis of Gougerot-Blum (PPLD). The histological findings were characteristic
      for PPLD, thus supporting the diagnosis. Topically administered corticosteroid
      led to a fast resolution of all symptoms. PPLD is not seen commonly in young
      patients and is most often described as responding poorly to treatment with
      topical corticosteroids. However, the case presented here shows both that PPLD
      can be seen in adolescence and that the condition may be treated successfully
      with an intense regime of topical corticosteroids. PPLD belongs to the group of
      pigmented purpuric dermatoses. The 5 most common pigmented purpuric dermatoses
      are summarized with respect to their clinical and paraclinical characteristics.

PMID- 29033824
TI  - Optical Coherence Tomography Evolution in a Case of X-Linked Juvenile
      Retinoschisis: 15 Years of Follow-Up.
AB  - PURPOSE: We present the evolution of X-linked juvenile retinoschisis (XLRS) in a
      male patient using optical coherence tomography (OCT) with a long-term follow-up
      time of 15 years. CASE DESCRIPTION: A 10-year-old male patient presented at the
      Medical Retina Department of our hospital complaining for blurred vision in both
      eyes. At the initial presentation in 2001, his best corrected visual acuity
      (BCVA) was 6/12 in both eyes on the Snellen chart. Based on clinical and OCT
      findings, the diagnosis of XLRS was made, and it was confirmed by genetic
      testing. No treatment was performed, but the patient was regularly examined. His
      BCVA and OCT findings remained relatively stable from 2001 to 2012, when BCVA
      decreased to 6/18 and 6/24 in the right and left eye, respectively. In 2016, his
      BCVA was 6/24 and 6/36 in right and left eye, respectively, while OCT depicted
      significant macular thinning, accompanied by irregularities of the foveal contour
      in both eyes. CONCLUSION: Patients with XLRS should be monitored regularly to
      evaluate the progression of the disease and manage the potential complications.

PMID- 29033826
TI  - Everyday Functioning Benefits from an Assisted Living Platform amongst Frail
      Older Adults and Their Caregivers.
AB  - Ambient assisted living technologies (AAL) are regarded as a promising solution
      to support aging in place. Yet, their efficacy has to be demonstrated in terms of
      benefits for independent living and for work conditions of caregivers. Hence, the
      purpose of this study was to assess the benefits of a multi-task AAL platform for
      both Frail older Individuals (FIs) and professional caregivers with respect to
      everyday functioning and caregiver burden. In this context, a 6-month field study
      involved 32 FIs living at home (half of them were equipped by the platform and
      the remaining half were not, as a control condition) and their caregivers.
      Everyday functioning measures were reported by frail participants and caregivers.
      Self-reported burden measures of caregiver were also collected. The main results
      showed that the caregiver's estimates of everyday functioning of equipped
      participants were unchanged across time, while they decreased for the control
      participants. Also, a reduction of self-reported objective burden was obtained
      after 6 months of AAL intervention for the equipped group, compared to the
      control group. Overall, these results highlighted the potential of AAL as a
      relevant environmental support for preventing both functional losses in FIs and
      objective burden professional caregiver.

PMID- 29033825
TI  - Acute Stress Affects the Expression of Hippocampal Mu Oscillations in an Age
      Dependent Manner.
AB  - Anxiolytic drugs are widely used in the elderly, a population particularly
      sensitive to stress. Stress, aging and anxiolytics all affect low-frequency
      oscillations in the hippocampus and prefrontal cortex (PFC) independently, but
      the interactions between these factors remain unclear. Here, we compared the
      effects of stress (elevated platform, EP) and anxiolytics (diazepam, DZP) on
      extracellular field potentials (EFP) in the PFC, parietal cortex and hippocampus
      (dorsal and ventral parts) of adult (8 months) and aged (18 months) Wistar rats.
      A potential source of confusion in the experimental studies in rodents comes from
      locomotion-related theta (6-12 Hz) oscillations, which may overshadow the direct
      effects of anxiety on low-frequency and especially on the high-amplitude
      oscillations in the Mu range (7-12 Hz), related to arousal. Animals were
      restrained to avoid any confound and isolate the direct effects of stress from
      theta oscillations related to stress-induced locomotion. We identified transient,
      high-amplitude oscillations in the 7-12 Hz range ("Mu-bursts") in the PFC,
      parietal cortex and only in the dorsal part of hippocampus. At rest, aged rats
      displayed more Mu-bursts than adults. Stress acted differently on Mu-bursts
      depending on age: it increases vs. decreases burst, in adult and aged animals,
      respectively. In contrast DZP (1 mg/kg) acted the same way in stressed adult and
      age animal: it decreased the occurrence of Mu-bursts, as well as their co
      occurrence. This is consistent with DZP acting as a positive allosteric modulator
      of GABAA receptors, which globally potentiates inhibition and has anxiolytic
      effects. Overall, the effect of benzodiazepines on stressed animals was to
      restore Mu burst activity in adults but to strongly diminish them in aged rats.
      This work suggests Mu-bursts as a neural marker to study the impact of stress and
      DZP on age.

PMID- 29033827
TI  - Excessive Sleepiness and Longer Nighttime in Bed Increase the Risk of Cognitive
      Decline in Frail Elderly Subjects: The MAPT-Sleep Study.
AB  - Objective: To identify self-reported sleep-wake disturbances that increase the
      risk of cognitive decline over 1-year follow-up in frail participants.
      Background: Risk factors for cognitive impairment need to be better identified
      especially at earliest stages of the pathogenesis. Sleep-wake disturbances may be
      critical factors to consider and were thus being assessed in this at-risk
      population for cognitive decline. Methods: Frail elderly participants aged >=70
      years were selected from a subsample of the Multi-domain Alzheimer Preventive
      Trial (MAPT) for a sleep assessment (MAPT-sleep study) at 18-month follow-up
      (M18). Sleep-wake disturbances were evaluated using a clinical interview
      (duration of daytime and nighttime sleep, time in bed, number of naps, and
      presence of clinically-defined sleep disorders) and numerous validated
      questionnaires [Epworth Sleepiness Scale for excessive daytime sleepiness (EDS),
      Insomnia Severity Scale and Berlin Questionnaire]. Cognitive decline was defined
      as a difference between the MMSE and cognitive composite scores at M24 and M36
      that was ranked in the lowest decile. Multivariate logistic regression models
      adjusted for several potential confounding factors were performed. Results: Among
      the 479 frail participants, 63 developed MMSE-cognitive decline and 50 cognitive
      composite score decrease between M24 and M36. Subjects with EDS had an increased
      risk of MMSE decline (OR = 2.46; 95% CI [1.28; 4.71], p = 0.007). A longer time
      spent in bed during night was associated with cognitive composite score decline
      (OR = 1.32 [1.03; 1.71], p = 0.03). These associations persisted when controlling
      for potential confounders. Patients with MMSE score decline and EDS had more
      naps, clinically-defined REM-sleep Behavior Disorder, fatigue and insomnia
      symptoms, while patients with cognitive composite score decline with longer time
      in bed had increased 24-h total sleep time duration but with higher wake time
      after onset. Conclusions: The risk of cognitive decline is higher in frailty
      subjects with EDS and longer nighttime in bed. Early detection of sleep-wake
      disturbances might help identifying frail subjects at risk of cognitive decline
      to further propose sleep health strategies to prevent cognitive impairment.
      http://www.clinicaltrials.gov NCT00672685; Date of registration May, 2nd 2008.

PMID- 29033828
TI  - Perspective Insights of Exosomes in Neurodegenerative Diseases: A Critical
      Appraisal.
AB  - Exosomes are small membranous entities of endocytic origin. Their production by a
      wide variety of cells in eukaryotes implicates their roles in the execution of
      essential processes, especially cellular communication. Exosomes are secreted
      under both physiological and pathophysiological conditions, and their actions on
      neighboring and distant cells lead to the modulations of cellular behaviors. They
      also assist in the delivery of disease causing entities, such as prions, alpha
      syn, and tau, and thus, facilitate spread to non-effected regions and accelerate
      the progressions of neurodegenerative diseases. The characterization of exosomes,
      provides information on aberrant processes, and thus, exosome analysis has many
      clinical applications. Because they are associated with the transport of
      different cellular entities across the blood-brain barrier (BBB), exosomes might
      be useful for delivering drugs and other therapeutic molecules to brain. Herein,
      we review roles played by exosomes in different neurodegenerative diseases, and
      the possibilities of using them as diagnostic biomarkers of disease progression,
      drug delivery vehicles and in gene therapy.

PMID- 29033829
TI  - Exercise Training Increases Parietal Lobe Cerebral Blood Flow in Chronic Stroke:
      An Observational Study.
AB  - Exercise is increasingly recommended as an essential component of stroke
      rehabilitation, yet uncertainty remains with respect to its direct effect on the
      cerebral vasculature. The current study first demonstrated the repeatability of
      pseudo-continuous arterial spin labeling (ASL) magnetic resonance imaging (MRI)
      in older adults with stroke, and then investigated the change in cerebrovascular
      function following a 6-month cardiovascular rehabilitation program. In the
      repeatability study, 12 participants at least 3 months post-stroke underwent two
      ASL imaging scans 1 month apart. In the prospective observational study, eight
      individuals underwent ASL imaging and aerobic fitness testing before and after a
      6-month cardiovascular rehabilitation program. Cerebral blood flow (CBF) and the
      spatial coefficient of variation of CBF (sCoV) were quantified to characterize
      tissue-level perfusion and large cerebral artery transit time properties,
      respectively. In repeat scanning, intraclass correlation (ICC) indicated moderate
      test-retest reliability for global gray matter CBF (ICC = 0.73) and excellent
      reliability for sCoV (ICC = 0.94). In the observational study, gray matter CBF
      increased after training (baseline: 40 +/- 13 vs. 6-month: 46 +/- 12 ml.100 g
      1.min-1, P = 0.036). The greatest change occurred in the parietal lobe (+18 +/-
      12%). Gray matter sCoV, however, did not change following training (P = 0.31).
      This study provides preliminary evidence that exercise-based rehabilitation in
      chronic stroke enhances tissue-level perfusion, without changing the relative
      hemodynamic properties of the large cerebral arteries.

PMID- 29033830
TI  - The Decrease of Uch-L1 Activity Is a Common Mechanism Responsible for Abeta 42
      Accumulation in Alzheimer's and Vascular Disease.
AB  - Alzheimer's disease (AD) is a multifactorial pathology causing common brain
      spectrum disorders in affected patients. These mixed neurological disorders not
      only include structural AD brain changes but also cerebrovascular lesions. The
      main aim of the present issue is to find the factors shared by the two
      pathologies. The decrease of ubiquitin C-terminal hydrolase L1 (Uch-L1), a major
      neuronal enzyme involved in the elimination of misfolded proteins, was observed
      in ischemic injury as well as in AD, but its role in the pathogenesis of AD is
      far to be clear. In this study we demonstrated that Uch-L1 inhibition induces
      BACE1 up-regulation and increases neuronal and apoptotic cell death in control as
      well as in transgenic AD mouse model subjected to Bengal Rose, a light-sensitive
      dye inducing that induces a cortical infarction through photo-activation. Under
      the same conditions we also found a significant activation of NF-kappaB. Thus,
      the restoration of Uch-L1 was able to completely prevent both the increase in
      BACE1 protein levels and the amount of cell death. Our data suggest that the Uch
      L1-mediated BACE1 up-regulation could be an important mechanism responsible for
      Abeta peptides accumulation in vascular injury and indicate that the modulation
      of the activity of this enzyme could provide new therapeutic strategies in AD.

PMID- 29033831
TI  - Accumulation of 123I-Ioflupane Is a Useful Marker of the Efficacy of Selegiline
      Monotherapy in Drug-Naive Parkinson's Disease.
AB  - Background: Selegiline enhances the patient's endogenous dopamine by inhibiting
      dopamine metabolism. The efficacy of selegiline monotherapy for drug-naive
      Parkinson's disease (PD) patients may depend on the degree of dopaminergic
      neuronal degeneration. 123I-Ioflupane single photon emission computed tomography
      (SPECT) and 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy are
      diagnostic methods to assess the pharmacological and pathological changes in PD.
      Objective: We examined the utility of these imaging methods to predict the
      efficacy of selegiline monotherapy for motor symptoms in drug-naive PD patients.
      Methods: We observed the efficacy of selegiline monotherapy in 28 drug-naive PD
      patients and compared the improvement in motor function and the imaging findings.
      These patients received selegiline monotherapy, and the amount was increased to
      the optimal dose in clinical practice. Motor function was assessed using the
      Unified Parkinson's Rating Scale (UPDRS) at baseline and at the stable dose.
      Imaging was performed before treatment, and the striatal Specific Binding Ratio
      (SBR) of the 123I-Ioflupane SPECT and the Heart-to-Mediastinum (H/M) ratio of the
      123I-MIBG myocardial scintigraphy were calculated. Both ratios were compared with
      improvements in scores for motor assessment using Pearson's correlation
      coefficient. Results: The mean UPDRS part III score significantly improved with
      at least 5.0 mg/day of selegiline. Further dose escalation did not improve the
      mean motor score. The percent improvement in the motor score from baseline showed
      a significant negative correlation with the SBR of average of the right and left
      striatum, but not with the H/M ratio. Multiple regression analysis using
      patient's background factors showed that percent improvement in the UPDRS part
      III score directly correlate with the SBR (p = 0.04), but not with the age (p =
      0.72), disease duration (p = 0.31), baseline UPDRS part III (p = 0.77) and the
      drug dose (p = 0.26). Conclusion: PD patients with a lower accumulation of 123I
      Ioflupane in the striatum can have greater improvement with selegiline
      monotherapy.

PMID- 29033832
TI  - Cyclotides Isolated from an Ipecac Root Extract Antagonize the Corticotropin
      Releasing Factor Type 1 Receptor.
AB  - Cyclotides are plant derived, cystine-knot stabilized peptides characterized by
      their natural abundance, sequence variability and structural plasticity. They are
      abundantly expressed in Rubiaceae, Psychotrieae in particular. Previously the
      cyclotide kalata B7 was identified to modulate the human oxytocin and vasopressin
      G protein-coupled receptors (GPCRs), providing molecular validation of the
      plants' uterotonic properties and further establishing cyclotides as valuable
      source for GPCR ligand design. In this study we screened a cyclotide extract
      derived from the root powder of the South American medicinal plant ipecac
      (Carapichea ipecacuanha) for its GPCR modulating activity of the corticotropin
      releasing factor type 1 receptor (CRF1R). We identified and characterized seven
      novel cyclotides. One cyclotide, caripe 8, isolated from the most active
      fraction, was further analyzed and found to antagonize the CRF1R. A nanomolar
      concentration of this cyclotide (260 nM) reduced CRF potency by ~4.5-fold. In
      contrast, caripe 8 did not inhibit forskolin-, or vasopressin-stimulated cAMP
      responses at the vasopressin V2 receptor, suggesting a CRF1R-specific mode-of
      action. These results in conjunction with our previous findings establish
      cyclotides as modulators of both classes A and B GPCRs. Given the diversity of
      cyclotides, our data point to other cyclotide-GPCR interactions as potentially
      important sources of drug-like molecules.

PMID- 29033833
TI  - Cell-Based Therapies for Tissue Fibrosis.
AB  - The development of tissue fibrosis in the context of a wound-healing response to
      injury is common to many chronic diseases. Unregulated or persistent fibrogenesis
      may lead to structural and functional changes in organs that increase the risk of
      significant morbidity and mortality. We will explore the natural history,
      epidemiology, and pathogenesis of fibrotic disease affecting the lungs, kidneys,
      and liver as dysfunction of these organs is responsible for a substantial
      proportion of global mortality. For many patients with end-stage disease, organ
      transplantation is the only effective therapy to prolong life. However, not all
      patients are candidates for the major surgical interventions and life-long
      immunosuppression required for a successful outcome and donor organs may not be
      available to meet the clinical need. We will provide an overview of the latest
      treatment strategies for these conditions and will focus on stem or progenitor
      cell-based therapies for which there is substantial pre-clinical evidence based
      on animal models as well as early phase clinical trials of cell-based therapy in
      man.

PMID- 29033835
TI  - Farnesol Has an Anti-obesity Effect in High-Fat Diet-Induced Obese Mice and
      Induces the Development of Beige Adipocytes in Human Adipose Tissue Derived
      Mesenchymal Stem Cells.
AB  - Brown adipocytes dissipate energy as heat and hence have an important therapeutic
      capacity for obesity. Development of brown-like adipocytes (also called beige) is
      also another attractive target for obesity treatment. Here, we investigated the
      effect of farnesol, an isoprenoid, on adipogenesis in adipocytes and on the
      browning of white adipose tissue (WAT) as well as on the weight gain of high-fat
      diet (HFD)-induced obese mice. Farnesol inhibited adipogenesis and the related
      key regulators including peroxisome proliferator-activated receptor gamma
      (PPARgamma) and CCAAT/enhancer binding protein alpha through the up-regulation of
      AMP-activated protein kinase in 3T3-L1 murine adipocytes and human adipose tissue
      derived mesenchymal stem cells (hAMSCs). Farnesol markedly increased the
      expression of uncoupling protein 1 and PPARgamma coactivator 1 alpha in
      differentiated hAMSCs. In addition, farnesol limited the weight gain in HFD obese
      mice and induced the development of beige adipocytes in both inguinal and
      epididymal WAT. These results suggest that farnesol could be a potential
      therapeutic agent for obesity treatment.

PMID- 29033834
TI  - TC299423, a Novel Agonist for Nicotinic Acetylcholine Receptors.
AB  - (E)-5-(Pyrimidin-5-yl)-1,2,3,4,7,8-hexahydroazocine (TC299423) is a novel agonist
      for nicotinic acetylcholine receptors (nAChRs). We examined its efficacy,
      affinity, and potency for alpha6beta2* (alpha6beta2-containing), alpha4beta2*,
      and alpha3beta4* nAChRs, using [125I]-epibatidine binding, whole-cell patch-clamp
      recordings, synaptosomal 86Rb+ efflux, [3H]-dopamine release, and [3H]
      acetylcholine release. TC299423 displayed an EC50 of 30-60 nM for alpha6beta2*
      nAChRs in patch-clamp recordings and [3H]-dopamine release assays. Its potency
      for alpha6beta2* in these assays was 2.5-fold greater than that for alpha4beta2*,
      and much greater than that for alpha3beta4*-mediated [3H]-acetylcholine release.
      We observed no major off-target binding on 70 diverse molecular targets. TC299423
      was bioavailable after intraperitoneal or oral administration. Locomotor assays,
      measured with gain-of-function, mutant alpha6 (alpha6L9'S) nAChR mice, show that
      TC299423 elicits alpha6beta2* nAChR-mediated responses at low doses. Conditioned
      place preference assays show that low-dose TC299423 also produces significant
      reward in alpha6L9'S mice, and modest reward in WT mice, through a mechanism that
      probably involves alpha6(non-alpha4)beta2* nAChRs. However, TC299423 did not
      suppress nicotine self-administration in rats, indicating that it did not block
      nicotine reinforcement in the dosage range that was tested. In a hot-plate test,
      TC299423 evoked antinociceptive responses in mice similar to those of nicotine.
      TC299423 and nicotine similarly inhibited mouse marble burying as a measure of
      anxiolytic effects. Taken together, our data suggest that TC299423 will be a
      useful small-molecule agonist for future in vitro and in vivo studies of nAChR
      function and physiology.

PMID- 29033837
TI  - Dioscin Inhibits HSC-T6 Cell Migration via Adjusting SDC-4 Expression: Insights
      from iTRAQ-Based Quantitative Proteomics.
AB  - Hepatic stellate cells (HSCs) migration, an important bioprocess, contributes to
      the development of liver fibrosis. Our previous studies have found the potent
      activity of dioscin against liver fibrosis by inhibiting HSCs proliferation,
      triggering the senescence and inducing apoptosis of activated HSCs, but the
      molecular mechanisms associated with cell migration were not clarified. In this
      work, iTRAQ (isobaric tags for relative and absolution quantitation)-based
      quantitative proteomics study was carried out, and a total of 1566 differentially
      expressed proteins with fold change >=2.0 and p < 0.05 were identified in HSC-T6
      cells treated by dioscin (5.0 MUg/mL). Based on Gene Ontology classification,
      String and KEGG pathway assays, the effects of dioscin to inhibit cell migration
      via regulating SDC-4 were carried out. The results of wound-healing, cell
      migration and western blotting assays indicated that dioscin significantly
      inhibit HSC-T6 cell migration through SDC-4-dependent signal pathway by affecting
      the expression levels of Fn, PKCalpha, Src, FAK, and ERK1/2. Specific SDC-4
      knockdown by shRNA also blocked HSC-T6 cell migration, and dioscin slightly
      enhanced the inhibiting effect. Taken together, the present work showed that SDC
      4 played a crucial role on HSC-T6 cell adhesion and migration of dioscin against
      liver fibrosis, which may be one potent therapeutic target for fibrotic diseases.

PMID- 29033838
TI  - The Target Residence Time of Antihistamines Determines Their Antagonism of the G
      Protein-Coupled Histamine H1 Receptor.
AB  - The pharmacodynamics of drug-candidates is often optimized by metrics that
      describe target binding (Kd or Ki value) or target modulation (IC50). However,
      these metrics are determined at equilibrium conditions, and consequently
      information regarding the onset and offset of target engagement and modulation is
      lost. Drug-target residence time is a measure for the lifetime of the drug-target
      complex, which has recently been receiving considerable interest, as target
      residence time is shown to have prognostic value for the in vivo efficacy of
      several drugs. In this study, we have investigated the relation between the
      increased residence time of antihistamines at the histamine H1 receptor (H1R) and
      the duration of effective target-inhibition by these antagonists. Hela cells,
      endogenously expressing low levels of the H1R, were incubated with a series of
      antihistamines and dissociation was initiated by washing away the unbound
      antihistamines. Using a calcium-sensitive fluorescent dye and a label free,
      dynamic mass redistribution based assay, functional recovery of the H1R
      responsiveness was measured by stimulating the cells with histamine over time,
      and the recovery was quantified as the receptor recovery time. Using these
      assays, we determined that the receptor recovery time for a set of antihistamines
      differed more than 40-fold and was highly correlated to their H1R residence
      times, as determined with competitive radioligand binding experiments to the H1R
      in a cell homogenate. Thus, the receptor recovery time is proposed as a cell
      based and physiologically relevant metric for the lead optimization of G protein
      coupled receptor antagonists, like the H1R antagonists. Both, label-free or real
      time, classical signaling assays allow an efficient and physiologically relevant
      determination of kinetic properties of drug molecules.

PMID- 29033836
TI  - Delivery of Antioxidant and Anti-inflammatory Agents for Tissue Engineered
      Vascular Grafts.
AB  - The treatment of patients with severe coronary and peripheral artery disease
      represents a significant clinical need, especially for those patients that
      require a bypass graft and do not have viable veins for autologous grafting.
      Tissue engineering is being investigated to generate an alternative graft. While
      tissue engineering requires surgical intervention, the release of pharmacological
      agents is also an important part of many tissue engineering strategies. Delivery
      of these agents offers the potential to overcome the major concerns for graft
      patency and viability. These concerns are related to an extended inflammatory
      response and its impact on vascular cells such as endothelial cells. This review
      discusses the drugs that have been released from vascular tissue engineering
      scaffolds and some of the non-traditional ways that the drugs are presented to
      the cells. The impact of antioxidant compounds and gasotransmitters, such as
      nitric oxide and carbon monoxide, are discussed in detail. The application of
      tissue engineering and drug delivery principles to biodegradable stents is also
      briefly discussed. Overall, there are scaffold-based drug delivery techniques
      that have shown promise for vascular tissue engineering, but much of this work is
      in the early stages and there are still opportunities to incorporate additional
      drugs to modulate the inflammatory process.

PMID- 29033839
TI  - Schisandra chinensis Stem Ameliorates 3-Nitropropionic Acid-Induced Striatal
      Toxicity via Activation of the Nrf2 Pathway and Inhibition of the MAPKs and NF
      kappaB Pathways.
AB  - The beneficial value of the stems of Schisandra chinensis (SSC) in neurological
      diseases is unclear. We examined whether SSC aqueous extract (SSCE) alleviates
      striatal toxicity in a 3-nitropropionic acid (3-NPA)-induced mouse model of
      Huntington's disease (HD). SSCE (75, 150, or 300 mg/kg/day, p.o.) was given daily
      before or after 3-NPA treatment. Pre- and onset-treatment with SSCE displayed a
      significant protective effect and pretreatment was more effective as assessed by
      neurological scores and survival rate. These effects were related to reductions
      in mean lesion area, cell death, succinate dehydrogenase activity, microglial
      activation, and protein expression of inflammatory factors including interleukin
      (IL)-1beta, IL-6, tumor necrosis factor-alpha, inducible nitric oxide synthase,
      and cyclooxygenase-2 in the striatum after 3-NPA treatment. Pretreatment with
      SSCE stimulated the nuclear factor erythroid 2-related factor 2 pathway and
      inhibited phosphorylation of the mitogen-activated protein kinase and nuclear
      factor-kappa B signaling pathways in the striatum after 3-NPA treatment. The
      gomisin A and schizandrin components of SSCE significantly reduced the
      neurological impairment and lethality induced by 3-NPA treatment. These results
      indicate for the first time that SSCE may effectively prevent 3-NPA-induced
      striatal toxicity during a wide therapeutic time window through anti-oxidative
      and anti-inflammatory activities. SSCE has potential value in preventive and
      therapeutic strategies for HD-like symptoms.

PMID- 29033840
TI  - Hydrogen Sulfide Inhibits Cigarette Smoke-Induced Endoplasmic Reticulum Stress
      and Apoptosis in Bronchial Epithelial Cells.
AB  - Background: Apoptosis of lung structural cells contributes to the process of lung
      damage and remodeling in chronic obstructive pulmonary disease (COPD). Our
      previous studies demonstrated that exogenous hydrogen sulfide (H2S) can reduce
      the lung tissue pathology score, anti-inflammation and anti-oxidation effects in
      COPD, but the effect of H2S in regulating cigarette smoke (CS) induced bronchial
      epithelial cell apoptosis and the underlying mechanisms are not clear.
      Objectives: To investigate the effect of H2S on CS induced endoplasmic reticulum
      stress (ERS) and bronchial epithelial cell apoptosis. Methods: Male Sprague
      Dawley rats randomly divided into four groups for treatment: control, CS, NaHS +
      CS, and propargylglycine (PPG) + CS. The rats in the CS group were exposed to CS
      generated from 20 commercial unfiltered cigarettes for 4 h/day, 7 days/week for 4
      months. Since the beginning of the third month, freshly prepared NaHS (14
      MUmol/kg) and PPG (37.5 mg/kg) were intraperitoneally administered 30 min before
      CS-exposure in the NaHS and PPG groups. 16HBE cells were pretreated with Taurine
      (10 mM), 5 mmol/L 4-phenylbutyric acid (4-PBA) or NaHS (100, 200, and 400 MUM)
      for 30 min, and then cells were exposed to 40 MUmol/L nicotine for 72 h. ERS
      markers (GRP94, GRP78) and ERS-mediated apoptosis markers 4-C/EBP homologous
      protein (CHOP), caspase-3 and caspase-12 were assessed in rat lung tissues and
      human bronchial epithelial cells. The apoptotic bronchial epithelial cells were
      detected by Hoechst staining in vitro and TUNEL staining in vivo. Results: In CS
      exposed rats, peritoneal injection of NaHS significantly inhibited CS induced
      overexpression ERS-mediated apoptosis markers and upregulation of apoptotic rate
      in rat lungs, and inhibiting the endogenous H2S production by peritoneal
      injection of PPG exacerbated these effects. In the nicotine-exposed bronchial
      epithelial cells, appropriate concentration of NaHS and ERS inhibitors taurine
      and 4-PBA inhibited nicotine-induced upregulation of apoptotic rate and
      overexpression of ERS-mediated apoptosis markers. Conclusion: H2S inhibited lung
      tissue damage by attenuating CS induced ERS in rat lung and exogenous H2S
      attenuated nicotine induced ERS-mediated apoptosis in bronchial epithelial cells.

PMID- 29033841
TI  - Pharmacodynamic Evaluation and PK/PD-Based Dose Prediction of Tulathromycin: A
      Potential New Indication for Streptococcus suis Infection.
AB  - Tulathromycin is the first member of the triamilide antimicrobial drugs that has
      been registered in more than 30 countries. The goal of this study is to provide a
      potential new indication of tulathromycin for Streptococcus suis infections. We
      investigated the pharmacokinetic and ex vivo pharmacodynamics of tulathromycin
      against experimental S. suis infection in piglets. Tulathromycin demonstrated a
      relatively long elimination half-life (74.1 h) and a mean residence time of 97.6
      h after a single intramuscular administration. The minimal inhibitory
      concentration (MIC) and bactericidal concentration in serum were markedly lower
      than those in broth culture, with Mueller-Hinton broth/serum ratios of 40.3 and
      11.4, respectively. The post-antibiotic effects were at 1.27 h (1* MIC) and 2.03
      h (4* MIC) and the post-antibiotic sub-MIC effect values ranged from 2.47 to 3.10
      h. The ratio of the area under the concentration-time curve divided by the MIC
      (AUC/MIC) correlated well with the ex vivo antimicrobial effectiveness of
      tulathromycin (R2 = 0.9711). The calculated AUC12h/MIC ratios in serum required
      to produce the net bacterial stasis, 1-log10 and 2-log10 killing activities were
      9.62, 18.9, and 32.7, respectively. Based on the results of Monte Carlo
      simulation, a dosage regimen of 3.56 mg/kg tulathromycin was estimated to be
      effective, achieving for a bacteriostatic activity against S. suis infection over
      5 days period. Tulathromycin may become a potential option for the treatment of
      S. suis infections.

PMID- 29033843
TI  - Commentary: The apolipoprotein A-I mimetic peptide, D-4F, restrains neointimal
      formation through heme oxygenase-1 up-regulation.

PMID- 29033842
TI  - Addressing the Challenges of Tuberculosis: A Brief Historical Account.
AB  - Tuberculosis (TB) is a highly contagious disease that still poses a threat to
      human health. Mycobacterium tuberculosis (MTB), the pathogen responsible for TB,
      uses diverse ways in order to survive in a variety of host lesions and to
      subsequently evade immune surveillance; as a result, fighting TB and its
      associated multidrug resistance has been an ongoing challenge. The aim of this
      review article is to summarize the historical sequence of drug development and
      use in the fight against TB, with a particular emphasis on the decades between
      World War II and the dawn of the twenty first century (2000).

PMID- 29033845
TI  - Commentary: Computerised interpretation of fetal heart rate during labour
      (INFANT): a randomised controlled trial.

PMID- 29033844
TI  - Syngeneic B16F10 Melanoma Causes Cachexia and Impaired Skeletal Muscle Strength
      and Locomotor Activity in Mice.
AB  - Muscle wasting has been emerging as one of the principal components of cancer
      cachexia, leading to progressive impairment of work capacity. Despite early
      stages melanomas rarely promotes weight loss, the appearance of metastatic and/or
      solid tumor melanoma can leads to cachexia development. Here, we investigated the
      B16F10 tumor-induced cachexia and its contribution to muscle strength and
      locomotor-like activity impairment. C57BL/6 mice were subcutaneously injected
      with 5 * 104 B16F10 melanoma cells or PBS as a Sham negative control. Tumor
      growth was monitored during a period of 28 days. Compared to Sham mice, tumor
      group depicts a loss of skeletal muscle, as well as significantly reduced muscle
      grip strength and epididymal fat mass. This data are in agreement with mild to
      severe catabolic host response promoted by elevated serum tumor necrosis factor
      alpha (TNF-alpha), interleukin-6 (IL-6) and lactate dehydrogenase (LDH) activity.
      Tumor implantation has also compromised general locomotor activity and decreased
      exploratory behavior. Likewise, muscle loss, and elevated inflammatory
      interleukin were associated to muscle strength loss and locomotor activity
      impairment. In conclusion, our data demonstrated that subcutaneous B16F10
      melanoma tumor-driven catabolic state in response to a pro-inflammatory
      environment that is associated with impaired skeletal muscle strength and
      decreased locomotor activity in tumor-bearing mice.

PMID- 29033846
TI  - Epithelial Markers aSMA, Krt14, and Krt19 Unveil Elements of Murine Lacrimal
      Gland Morphogenesis and Maturation.
AB  - As an element of the lacrimal apparatus, the lacrimal gland (LG) produces the
      aqueous part of the tear film, which protects the eye surface. Therefore, a
      defective LG can lead to serious eyesight impairment. Up to now, little is known
      about LG morphogenesis and subsequent maturation. In this study, we delineated
      elements of the cellular and molecular events involved in LG formation by using
      three epithelial markers, namely aSMA, Krt14, and Krt19. While aSMA marked a
      restricted epithelial population of the terminal end buds (TEBs) in the forming
      LG, Krt14 was found in the whole embryonic LG epithelial basal cell layer.
      Interestingly, Krt19 specifically labeled the presumptive ductal domain and
      subsequently, the luminal cell layer. By combining these markers, the Fucci
      reporter mouse strain and genetic fate mapping of the Krt14+ population, we
      demonstrated that LG epithelium expansion is fuelled by a patterned cell
      proliferation, and to a lesser extent by epithelial reorganization and possible
      mesenchymal-to-epithelial transition. We pointed out that this epithelial
      reorganization, which is associated with apoptosis, regulated the lumen
      formation. Finally, we showed that the inhibition of Notch signaling prevented
      the ductal identity from setting, and led to a LG covered by ectopic TEBs. Taken
      together our results bring a deeper understanding on LG morphogenesis, epithelial
      domain identity, and organ expansion.

PMID- 29033847
TI  - A Monetary Reward Alters Pacing but Not Performance in Competitive Cyclists.
AB  - Money has frequently been used as an extrinsic motivator since it is assumed that
      humans are willing to invest more effort for financial reward. However, the
      influence of a monetary reward on pacing and performance in trained athletes is
      not well-understood. Therefore, the aim of this study was to analyse the
      influence of a monetary reward in well-trained cyclists on their pacing and
      performance during short and long cycling time trials (TT). Twentythree cyclists
      (6 ?, 17 ?) completed 4 self-paced time trials (TTs, 2 short: 4 km and 6 min; 2
      long: 20 km and 30 min); in a randomized order. Participants were separated into
      parallel, non-randomized "rewarded" and "non-rewarded" groups. Cyclists in the
      rewarded group received a monetary reward based on highest mean power output
      across all TTs. Cyclists in the non-rewarded group did not receive a monetary
      reward. Overall performance was not significantly different between groups in
      short or long TTs (p > 0.48). Power output showed moderatly lower effect sizes at
      comencement of the short TTs (Pmeandiff = 36.6 W; d > 0.44) and the 20 km TT
      (Pmeandiff = 22.6 W; d = 0.44) in the rewarded group. No difference was observed
      in pacing during the 30 min TT (p = 0.95). An external reward seems to have
      influenced pacing at the commencement of time trials. Participants in the non
      rewarded group adopted a typical parabolic shaped pattern, whereas participants
      in the rewarded group started trials more conservatively. Results raise the
      possibility that using money as an extrinsic reward may interfere with regulatory
      processes required for effective pacing.

PMID- 29033848
TI  - Editorial: Physiology in Extreme Conditions: Adaptations and Unexpected
      Reactions.

PMID- 29033849
TI  - Study on the Effect of Wing Bud Chitin Metabolism and Its Developmental Network
      Genes in the Brown Planthopper, Nilaparvata lugens, by Knockdown of TRE Gene.
AB  - The brown planthopper, Nilaparvata lugens is one of the most serious pests of
      rice, and there is so far no effective way to manage this pest. However, RNA
      interference not only can be used to study gene function, but also provide
      potential opportunities for novel pest management. The development of wing plays
      a key role in insect physiological activities and mainly involves chitin. Hence,
      the regulating role of trehalase (TRE) genes on wing bud formation has been
      studied by RNAi. In this paper, the activity levels of TRE and the contents of
      the two sugars trehalose and glucose were negatively correlated indicating the
      potential role of TRE in the molting process. In addition, NlTRE1-1 and NlTRE2
      were expressed at higher levels in wing bud tissue than in other tissues, and
      abnormal molting and wing deformity or curling were noted 48 h after the insect
      was injected with any double-stranded TRE (dsTRE), even though different TREs
      have compensatory functions. The expression levels of NlCHS1b, NlCht1, NlCht2,
      NlCht6, NlCht7, NlCht8, NlCht10, NlIDGF, and NlENGase decreased significantly 48
      h after the insect was injected with a mixture of three kinds of dsTREs.
      Similarly, the TRE inhibitor validamycin can inhibit NlCHS1 and NlCht gene
      expression. However, the wing deformity was the result of the NlIDGF, NlENGase,
      NlAP, and NlTSH genes being inhibited when a single dsTRE was injected. These
      results demonstrate that silencing of TRE gene expression can lead to wing
      deformities due to the down-regulation of the AP and TSH genes involved in wing
      development and that the TRE inhibitor validamycin can co-regulate chitin
      metabolism and the expression of wing development-related genes in wing bud
      tissue. The results provide a new approach for the prevention and management of
      N. lugens.

PMID- 29033851
TI  - Effects of Alpha-Lactalbumin or Whey Protein Isolate on Muscle Damage, Muscle
      Pain, and Mood States Following Prolonged Strenuous Endurance Exercise.
AB  - This study compared the effect of alpha-lactalbumin and whey protein on muscle
      damage, muscle pain, and mood states during short term recovery following
      strenuous prolonged exercise. In a two-stage crossover counterbalanced design, 12
      endurance male runners were recruited (age: 30.4 +/- 2.8 year, height: 172.7 +/-
      5.6 cm, body mass: 66.7 +/- 6.5 kg, VO2max: 58.0 +/- 6.9 ml/kg-/min), ran for 90
      min at 70% VO2max, and followed by a 4-h recovery. Two treatments
      (carbohydrate+alpha-lactalbumin, CA; carbohydrate+whey protein isolate, CW) were
      applied during the main trials. During the first 2-h of recovery, CHO was served
      at the rate of 0.66 g/kg/h and PRO at 0.34 g/kg/h every 30 min. Creatine kinase
      (CK), interleukin-6 (IL-6), salivary cortisol, rating of muscle pain, pressure
      pain threshold (PPT), and mood states were evaluated before (Pre-ex), immediately
      (Post-ex0), 2 h (Post-ex2h) and 4 h (Post-ex4h) after exercise. 24 h after
      exercise (Post-ex24h), CK and IL-6, muscle pain, and PPT were evaluated. Compared
      with Pre-ex, Post-ex24h CK was higher in both trials of CA (398.16 +/- 41.37 vs.
      184.77 +/- 22.68 IU/L, P = 0.039) and CW (418.17 +/- 67.86 vs. 202.41 +/- 22.26
      IU/L, P = 0.037). IL-6 was also higher than Pre-ex at Post-ex0 and Post-ex2h in
      trials of CA (Post-ex0 vs. Pre-ex0: 7.87 +/- 0.74 vs. 1.69 +/- 0.23, P < 0.01;
      Post-ex2h vs. Pre-ex0: 5.39 +/- 0.88 vs. 1.69 +/- 0.23, P = 0.02) and CW (Post
      ex0 vs. Pre-ex0: 8.63 +/- 1.06 vs. 1.59 +/- 0.19, P < 0.01; Post-ex2h vs. Pre
      ex0: 5.75 +/- 1.33 vs. 1.59 +/- 0.19, P < 0.01). No difference was found in CK
      and IL-6 between two trials at all time points (all P > 0.05). Compared with Pre
      ex0, salivary cortisol was elevated at Post-ex0 in both trials (CA: 0.96 +/- 0.13
      vs. 0.41 +/- 0.05 ng/ml, P < 0.01; CW: 1.15 +/- 0.18 vs. 0.43 +/- 0.06 ng/ml, P <
      0.01) and was lower at Post-ex24h than Pre-ex in CA trial (0.17 +/- 0.02 vs. 0.41
      +/- 0.05 ng/ml, P < 0.01). Compared with CW, PPT was higher at Post-2h in CA
      trial (31.55 +/- 3.09 vs. 26.99 +/- 2.32 N/cm2, P < 0.01). Compared with Post
      ex0, feeling of fatigue was lower at Post-ex2h (P = 0.014) and Post-ex4h (P <
      0.01) in CA, while it was lower at Post-ex4h (P = 0.038) in CW. Compared with CW,
      feeling of fatigue was marginally lower in the CA trial at Post-ex2h (P = 0.056).
      In conclusion, compared with the co-ingestion of CHO and whey PRO isolate, co
      ingestion of CHO and alpha-lactalbumin reduced sensitivity to the muscle pain,
      attenuated feeling of fatigue and was more beneficial to reduce the feeling of
      fatigue and cortisol responses during 4-h recovery following 90-min running at
      70% VO2max.

PMID- 29033850
TI  - Designing Dietary Recommendations Using System Level Interactomics Analysis and
      Network-Based Inference.
AB  - Background: A range of computational methods that rely on the analysis of genome
      wide expression datasets have been developed and successfully used for drug
      repositioning. The success of these methods is based on the hypothesis that
      introducing a factor (in this case, a drug molecule) that could reverse the
      disease gene expression signature will lead to a therapeutic effect. However, it
      has also been shown that globally reversing the disease expression signature is
      not a prerequisite for drug activity. On the other hand, the basic idea of
      significant anti-correlation in expression profiles could have great value for
      establishing diet-disease associations and could provide new insights into the
      role of dietary interventions in disease. Methods: We performed an integrated
      analysis of publicly available gene expression profiles for foods, diseases and
      drugs, by calculating pairwise similarity scores for diet and disease gene
      expression signatures and characterizing their topological features in protein
      protein interaction networks. Results: We identified 485 diet-disease pairs where
      diet could positively influence disease development and 472 pairs where specific
      diets should be avoided in a disease state. Multiple evidence suggests that
      orange, whey and coconut fat could be beneficial for psoriasis, lung
      adenocarcinoma and macular degeneration, respectively. On the other hand,
      fructose-rich diet should be restricted in patients with chronic intermittent
      hypoxia and ovarian cancer. Since humans normally do not consume foods in
      isolation, we also applied different algorithms to predict synergism; as a
      result, 58 food pairs were predicted. Interestingly, the diets identified as anti
      correlated with diseases showed a topological proximity to the disease proteins
      similar to that of the corresponding drugs. Conclusions: In conclusion, we
      provide a computational framework for establishing diet-disease associations and
      additional information on the role of diet in disease development. Due to the
      complexity of analyzing the food composition and eating patterns of individuals
      our in silico analysis, using large-scale gene expression datasets and network
      based topological features, may serve as a proof-of-concept in nutritional
      systems biology for identifying diet-disease relationships and subsequently
      designing dietary recommendations.

PMID- 29033852
TI  - Activation of Casein Kinase II by Gallic Acid Induces BIK-BAX/BAK-Mediated ER
      Ca++-ROS-Dependent Apoptosis of Human Oral Cancer Cells.
AB  - Induction of the generation of endoplasmic reticulum (ER) calcium (Ca++)-mediated
      reactive oxygen species (ROS) by gallic acid (GA) has been implicated in the
      mitochondrial apoptotic death of human oral cancer (OC) cells, but the molecular
      mechanism by which GA causes ER Ca++ release of OC cells to undergo cell death
      remains unclear. Here, we report that GA-induced phosphorylation of B-cell
      lymphoma 2 (BCL-2)-interacting killer (BIK) (threonine (Thr) 33/Serine (Ser) 35)
      and p53 (Ser 15 and Ser 392), Bcl-2-associated x protein (BAX)/BCL-2 antagonist
      killer 1 (BAK) oligomerization on the ER and mitochondria, rising of cytosolic
      Ca++ and ROS, cytochrome c (Cyt c) release from the mitochondria, Psim loss, and
      apoptosis were suppressed in cells co-treated with a specific inhibitor of casein
      kinase II (CK II) (4,5,6,7-tetrabromobenzotriazole). Small interfering RNA
      (siRNA)-mediated suppression of BIK inhibited GA-induced oligomeric complex of
      BAX/BAK in the ER and mitochondria, increase of cytosolic Ca++ and ROS, and
      apoptosis, but did not attenuate the increase in the level of Ser 15-phosphated
      p53 induced by GA. Blockade of p53 expression by short hairpin RNA suppressed
      BAX/BAK oligomerization and ER Ca++-ROS-associated apoptosis induced by GA but
      did not affect GA-induced phospho-BIK (Thr 33/Ser 35) levels. Induction of
      mitochondrial Cyt c release and ROS generation, increased cytosolic Ca++ level,
      and apoptosis by GA was attenuated by expression of the BAX or BAK siRNA. Over
      expression of BCL-2 (but not BCL-XL) inhibited formation of ER oligomeric BAX/BAK
      by GA. Our results demonstrated that activation of the CK II by GA is required
      for the BIK-mediated ROS-dependent apoptotic activity of ER-associated BAX/BAK.

PMID- 29033853
TI  - Proinflammatory Effect of High Glucose Concentrations on HMrSV5 Cells via the
      Autocrine Effect of HMGB1.
AB  - Background: Peritoneal fibrosis, in which inflammation and apoptosis play crucial
      pathogenic roles, is a severe complication associated with the treatment of
      kidney failure with peritoneal dialysis (PD) using a glucose-based dialysate.
      Mesothelial cells (MCs) take part in the inflammatory processes by producing
      various cytokines and chemokines, such as monocyte chemoattractant protein 1 (MCP
      1) and interleukin 8 (IL-8). The apoptosis of MCs induced by high glucose levels
      also contributes to complications of PD. High mobility group protein B1 (HMGB1)
      is an inflammatory factor that has repeatedly been proven to be related to the
      occurrence of peritoneal dysfunction. Aim: In this study, we aimed to explore the
      effect and underlying mechanism of endogenous HMGB1 in high-glucose-induced MC
      injury. Methods: The human peritoneal MC line, HMrSV5 was cultured in high
      glucose medium and incubated with recombinant HMGB1. Cellular expression of HMGB1
      was blocked using HMGB1 small interfering RNA (siRNA). Apoptosis and production
      of inflammatory factors as well as the potential intermediary signaling pathways
      were examined. Results: The major findings of these analyses were: (1) MCs
      secreted HMGB1 from the nucleus during exposure to high glucose levels; HMGB1
      acted in an autocrine fashion on the MCs to promote the production of MCP-1 and
      IL-8; (2) HMGB1 had little effect on high-glucose-induced apoptosis of the MCs;
      and (3) HMGB1-mediated MCP-1 and IL-8 production depended on the activation of
      MAPK signaling pathways. In conclusion, endogenous HMGB1 plays an important role
      in the inflammatory reaction induced by high glucose on MCs via mitogen-activated
      protein kinase (MAPK) signaling pathways, but it seems to have little effect on
      high-glucose-induced apoptosis.

PMID- 29033854
TI  - High-Temperature Tolerance of Photosynthesis Can Be Linked to Local Electrical
      Responses in Leaves of Pea.
AB  - It is known that numerous stimuli induce electrical signals which can increase a
      plant's tolerance to stressors, including high temperature. However, the
      physiological role of local electrical responses (LERs), i.e., responses in the
      zone of stimulus action, in the plant's tolerance has not been sufficiently
      investigated. The aim of a current work is to analyze the connection between
      parameters of LERs with the thermal tolerance of photosynthetic processes in pea.
      Electrical activity and photosynthetic parameters in pea leaves were registered
      during transitions of air temperature in a measurement head (from 23 to 30
      degrees C, from 30 to 40 degrees C, from 40 to 45 degrees C, and from 45 to 23
      degrees C). This stepped heating decreased a photosynthetic assimilation of CO2
      and induced generation of LERs in the heated leaf. Amplitudes of LERs, quantity
      of responses during the heating and the number of temperature transition, which
      induced the first generation of LERs, varied among different pea plants.
      Parameters of LERs were weakly connected with the photosynthetic assimilation of
      CO2 during the heating; however, a residual photosynthetic activity after a
      treatment by high temperatures increased with the growth of amplitudes and
      quantity of LERs and with lowering of the number of the heating transition,
      inducing the first electrical response. The effect was not connected with a
      photosynthetic activity before heating; similar dependences were also observed
      for effective and maximal quantum yields of photosystem II after heating. We
      believe that the observed effect can reflect a positive influence of LERs on the
      thermal tolerance of photosynthesis. It is possible that the process can
      participate in a plant's adaptation to stressors.

PMID- 29033855
TI  - Implicit Recognition of Familiar and Unfamiliar Faces in Schizophrenia: A Study
      of the Skin Conductance Response in Familiarity Disorders.
AB  - OBJECTIVE: Familiarity is a subjective sensation that contributes to person
      recognition. This process is described as an emotion-based memory-trace of
      previous meetings and could be disrupted in schizophrenia. Consequently,
      familiarity disorders could be involved in the impaired social interactions
      observed in patients with schizophrenia. Previous studies have primarily focused
      on famous people recognition. Our aim was to identify underlying features, such
      as emotional disturbances, that may contribute to familiarity disorders in
      schizophrenia. We hypothesize that patients with familiarity disorders will
      exhibit a lack of familiarity that could be detected by a flattened skin
      conductance response (SCR). METHOD: The SCR was recorded to test the hypothesis
      that emotional reactivity disturbances occur in patients with schizophrenia
      during the categorization of specific familiar, famous and unknown faces as male
      or female. Forty-eight subjects were divided into the following 3 matched groups
      with 16 subjects per group: control subjects, schizophrenic people with
      familiarity disorder, and schizophrenic people without familiarity disorders.
      RESULTS: Emotional arousal is reflected by the skin conductance measures. The
      control subjects and the patients without familiarity disorders experienced a
      differential emotional response to the specific familiar faces compared with that
      to the unknown faces. Nevertheless, overall, the schizophrenic patients without
      familiarity disorders showed a weaker response across conditions compared with
      the control subjects. In contrast, the patients with familiarity disorders did
      not show any significant differences in their emotional response to the faces,
      regardless of the condition. CONCLUSION: Only patients with familiarity disorders
      fail to exhibit a difference in emotional response between familiar and non
      familiar faces. These patients likely emotionally process familiar faces
      similarly to unknown faces. Hence, the lower feelings of familiarity in
      schizophrenia may be a premise enabling the emergence of familiarity disorders.

PMID- 29033856
TI  - Possible Facilitative Effects of Repeated Anodal Transcranial Direct Current
      Stimulation on Functional Outcome 1 Month Later in Schizophrenia: An Open Trial.
AB  - : Recent research on neuromodulation techniques, such as transcranial direct
      current stimulation (tDCS), for the treatment of schizophrenia has mainly focused
      on psychotic symptoms. We aimed to determine whether repetitive tDCS is
      efficacious in improving determinants of outcome, such as cognitive function,
      daily living skills, and depressive mood in patients with schizophrenia. Twenty
      eight patients underwent tDCS (2 mA * 20 min) two times per day for 5 consecutive
      days. The anodal electrode was placed over the left dorsolateral prefrontal
      cortex while the cathodal electrode was placed over the right supraorbital
      region. One month after the last stimulation, there was a significant improvement
      on cognitive function, measured by the brief assessment of cognition in
      schizophrenia (d = 0.49). Significant effects were also shown on daily living
      skills (functional capacity), measured by the UCSD performance-based skills
      assessment-brief (d = 0.70). Depressive symptoms, measured by the Calgary
      depression rating scale, as well as psychotic symptoms measured by on the
      positive and negative syndrome scale positive and general psychopathology
      subscales also responded to the treatment (d = 0.38, d = 0.48, and d = 0.50,
      respectively). This is the first study to suggest that tDCS with the anodal
      electrode on the left prefrontal cortex improves functional capacity and
      depressive symptoms in patients with schizophrenia. These results may add to the
      concept that tDCS provides a strategy to enhance functional outcomes in patients
      with schizophrenia. TRIAL REGISTRATION: https://upload.umin.ac.jp/cgi-open
      bin/ctr/ctr_view.cgi?recptno=R000018556, UMIN000015953.

PMID- 29033857
TI  - An Update Overview on Brain Imaging Studies of Internet Gaming Disorder.
AB  - There are a growing number of studies on structural and functional brain
      mechanisms underlying Internet gaming disorder (IGD). Recent functional magnetic
      resonance imaging studies showed that IGD adolescents and adults had reduced gray
      matter volume in regions associated with attention motor coordination executive
      function and perception. Adolescents with IGD showed lower white matter (WM)
      integrity measures in several brain regions that are involved in decision-making,
      behavioral inhibition, and emotional regulation. IGD adolescents had also
      disruption in the functional connectivity in areas responsible for learning
      memory and executive function, processing of auditory, visual, and somatosensory
      stimuli and relay of sensory and motor signals. IGD adolescents also had
      decreased functional connectivity of PFC-striatal circuits, increased risk-taking
      choices, and impaired ability to control their impulses similar to other impulse
      control disorders. Recent studies indicated that altered executive control
      mechanisms in attention deficit hyperactivity disorder (ADHD) would be a
      predisposition for developing IGD. Finally, patients with IGD have also shown an
      increased functional connectivity of several executive control brain regions that
      may related to comorbidity with ADHD and depression. The behavioral addiction
      model argues that IGD shows the features of excessive use despite adverse
      consequences, withdrawal phenomena, and tolerance that characterize substance use
      disorders. The evidence supports the behavioral addiction model of IGD by showing
      structural and functional changes in the mechanisms of reward and craving (but
      not withdrawal) in IGD. Future studies need to investigate WM density and
      functional connectivity in IGD in order to validate these findings. Furthermore,
      more research is required about the similarity in neurochemical and
      neurocognitive brain circuits in IGD and comorbid conditions such as ADHD and
      depression.

PMID- 29033858
TI  - HoNOSCA-D As a Measure of the Severity of Diagnosed Mental Disorders in Children
      and Adolescents-Psychometric Properties of the German Translation.
AB  - The Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA),
      in use worldwide, is a 13-item measure assessing the biopsychosocial severity of
      mental health problems in children and adolescents. This article introduces the
      authorized German-language version of HoNOSCA, the HoNOSCA-D, and examines and
      discusses its psychometric properties based on a clinical sample of 1,533
      children and adolescents aged 4;0 to 17;11 years. For the HoNOSCA-D total score
      (severity of mental health problems), internal consistency (Cronbach's alpha) was
      0.63. The discriminative power of the items ranged from 0.07 to 0.44; the average
      interitem correlation was 0.11. Due to this stochastic independence, calculation
      of a total severity index is acceptable. Using factor analysis, the principal
      axis factoring and varimax rotation resulted in a four-factor structure, which
      with a Kaiser-Meyer-Olkin measure of sampling adequacy of 0.684 explained 30.62%
      of total variance. The convergent correlations with the German-language parent
      report version of the Strengths and Difficulties Questionnaire were as expected
      and showed a medium effect size. Gender and age differences in the HoNOSCA-D
      total score were small. Regarding the 13 items gender and age differences were
      negligible to medium. The highest severity was found for schizophrenia and
      psychotic disorders, followed by affective disorders and social behavior
      disorders. Overall, validity of HoNOSCA-D was clearly supported.

PMID- 29033859
TI  - Multi-Watt Near-Infrared Phototherapy for the Treatment of Comorbid Depression:
      An Open-Label Single-Arm Study.
AB  - BACKGROUND: The treatment of depression has been hampered by low efficacy of
      antidepressant medications and safety concerns with alternative modalities.
      Recent work demonstrated that multi-Watt transcranial near-infrared light therapy
      (NILT) can effectively treat traumatic brain injury (TBI). The current objective
      is to explore multi-Watt NILT efficacy in a proof-of-concept study as a treatment
      for depression. METHODS: Thirty-nine sequential patients treated for TBI between
      March 2013 and May 2017 provided depression self-assessment data and/or were
      administered the Hamilton depression rating scale. Each completed the Quick
      Inventory of Depression Symptomatology-Self Report (QIDS) before and after
      treatment. Patients received multi-Watt NILT using near-infrared lasers (810/980
      nm at 8-15 W) applied to forehead and temporal regions bilaterally for 9-12 min
      to each area. Pre- and posttreatment scores were analyzed by paired t-tests.
      RESULTS: All met QIDS criteria for mild to severe depression and 69% had prior
      antidepressant trials. For 36 of the 39 patients, after 16.82 +/- 6.26
      treatments, QIDS scores indicated a robust response (decrease of QIDS total score
      by >=50%). For 32 of 39 patients, posttreatment QIDS scores indicated a remission
      from depression (decrease of QIDS total score <=5). Overall, the QIDS score fell
      from 14.10 +/- 3.39 to 3.41 +/- 3.30 SD (p = 6.29 * 10-19). With 12 or fewer
      treatments, QIDS score dropped from 14.83 +/- 2.55 to 4.17 +/- 3.93. Patients
      receiving >=13 treatments showed a change in QIDS score from 13.67 +/- 3.64 to
      3.11 +/- 3.14. Those (N = 15) who received the entire treatment course within <=8
      weeks (5.33 +/- 1.72 weeks) showed a change in QIDS score from 13.86 +/- 3.14 to
      4.5 +/- 3.94. Suicidal ideation resolved in all, but two patients. Patients
      remained in remission for up to 55 months after a single course of treatment.
      CONCLUSION: This is the first report of high-powered NILT showing efficacy for
      depression. Multi-Watt NILT showed far greater efficacy and persistent benefit
      compared to low-power (<1 Watt) infrared light treatments. Patients saw benefit
      often within four treatments and resolution of depressive symptoms occurred
      within 4 weeks for some. These data raise an intriguing possibility-that multi
      Watt NILT may be a safe, effective, and rapid treatment for depression comorbid
      with TBI and possibly primary major depression disorder. A double-blind, placebo
      controlled trial is warranted to verify these proof-of-concept data.

PMID- 29033860
TI  - Olfactory Functioning and Depression: A Systematic Review.
AB  - BACKGROUND: Research has demonstrated a reduction in olfactory functioning in
      patients with schizophrenia. This research has led to examination of olfactory
      functioning in other mental disorders, such as depression. There is a great deal
      of variation in the results generated from such research, and it remains unclear
      as to how olfactory functioning is associated with or impacted by depression.
      METHOD: The current review examined the literature in accordance with PRISMA
      guidelines in order to generate a better understanding of this relationship and
      to identify if and what aspects of olfactory processing are altered. Through
      examination of the available literature from the databases PubMed, Ovid Medline,
      CINAL, and PsychINFO, 15 manuscripts were selected to determine if there was a
      difference in olfactory processing-specifically central and peripheral processing
      between depressed individuals and non-depressed controls. RESULTS: The comparison
      of the 15 studies showed that the majority of studies (9/15, 60%) found a
      difference in overall olfactory functioning between depressed individuals and non
      depressed controls (p < 0.05). LIMITATIONS: There is still a lack of definitive
      conclusions due to variation of which olfactory process was altered. CONCLUSION:
      Given the differences in the methodology and design of these studies, a possible
      solution that could eliminate the lack of clarity and reduce variation would be
      to adhere to a single, thorough methodology that examines and separates central
      and peripheral olfactory processing. Future research employing a uniform and
      validated methodology could provide more definitive conclusions as to how and if
      olfactory functioning is related depression.

PMID- 29033862
TI  - The Impact of Bodily States on Divergent Thinking: Evidence for a Control
      Depletion Account.
AB  - Given previous evidence that bodily states can impact basic cognitive processes,
      we asked whether such impact can also be demonstrated for creative cognition. In
      particular, we had participants perform a design improvement task and a
      consequences imagination task while standing up, walking in a predetermined
      pattern, or walking freely. Results show better divergent-thinking performance
      with unconstrained than with constrained walking, and better performance for
      walking than for standing. A second experiment assessed performance in an
      alternative uses task and a figural combination task while participants were
      lying, sitting, or standing. Results showed better performance when standing up
      than when lying or sitting. Taken altogether, these observations provide evidence
      for an approach in terms of cognitive-control depletion: the more a bodily
      activity exhausts control resources, the better divergent thinking can unfold,
      presumably because reduced top-down control brings more ideas into play.

PMID- 29033863
TI  - The Peaceful Co-existence of Input Frequency and Structural Intervention Effects
      on the Comprehension of Complex Sentences in German-Speaking Children.
AB  - The predictions of two contrasting approaches to the acquisition of transitive
      relative clauses were tested within the same groups of German-speaking
      participants aged from 3 to 5 years old. The input frequency approach predicts
      that object relative clauses with inanimate heads (e.g., the pullover that the
      man is scratching) are comprehended earlier and more accurately than those with
      an animate head (e.g., the man that the boy is scratching). In contrast, the
      structural intervention approach predicts that object relative clauses with two
      full NP arguments mismatching in number (e.g., the man that the boys are
      scratching) are comprehended earlier and more accurately than those with number
      matching NPs (e.g., the man that the boy is scratching). These approaches were
      tested in two steps. First, we ran a corpus analysis to ensure that object
      relative clauses with number-mismatching NPs are not more frequent than object
      relative clauses with number-matching NPs in child directed speech. Next, the
      comprehension of these structures was tested experimentally in 3-, 4-, and 5-year
      olds respectively by means of a color naming task. By comparing the predictions
      of the two approaches within the same participant groups, we were able to uncover
      that the effects predicted by the input frequency and by the structural
      intervention approaches co-exist and that they both influence the performance of
      children on transitive relative clauses, but in a manner that is modulated by
      age. These results reveal a sensitivity to animacy mismatch already being
      demonstrated by 3-year-olds and show that animacy is initially deployed more
      reliably than number to interpret relative clauses correctly. In all age groups,
      the animacy mismatch appears to explain the performance of children, thus,
      showing that the comprehension of frequent object relative clauses is enhanced
      compared to the other conditions. Starting with 4-year-olds but especially in 5
      year-olds, the number mismatch supported comprehension-a facilitation that is
      unlikely to be driven by input frequency. Once children fine-tune their
      sensitivity to verb agreement information around the age of four, they are also
      able to deploy number marking to overcome the intervention effects. This study
      highlights the importance of testing experimentally contrasting theoretical
      approaches in order to characterize the multifaceted, developmental nature of
      language acquisition.

PMID- 29033861
TI  - Neuropsychological Impairment in Detoxified Alcohol-Dependent Subjects with
      Preserved Psychosocial Functioning.
AB  - BACKGROUND: Chronic alcoholism and its related cognitive impairments are
      associated with increased social, relational, and professional deficits which
      have a variable overall impact on social integration. These impairments are known
      to have varying severities and have rarely been studied among healthy alcohol
      dependent subjects with preserved psychosocial functioning. Thus, the objective
      of this study is to describe neuropsychological performance in this particular
      population. METHOD: Twenty-nine socially adjusted alcohol-dependent men,
      hospitalized for a first or second withdrawal and abstinent for 3 weeks minimum,
      were compared to 29 healthy non-alcoholic controls. All subjects underwent
      clinical and psychiatric examination, neuropsychological tests of memory (M),
      working memory (WM), and executive functions (EF). Comparisons were performed
      using Student's t-tests or Mann-Whitney U tests. RESULTS: No group differences
      were found on the Self-Reported Social Adjustment Scale (SAS-SR) or in the Mini
      Mental State Examination. Compared to controls, patients had greater episodic,
      spatial, and WM deficits as well as slightly altered executive functions. In
      contrast, their executive functions (spontaneous flexibility, criteria
      generation, rule maintenance, and inhibitory control) were relatively preserved.
      CONCLUSION: Our sample of socially and professionally integrated alcoholic
      patients shows fewer cognitive deficits than described in previous studies. Our
      results suggest that early on, alcohol-dependent subjects develop compensatory
      adaptation processes to preserve social function and adaptation. Minor cognitive
      impairments should be screened early in the disease to integrate cognitive
      interventions into the health-care plan to thus eventually prevent further socio
      professional marginalization.

PMID- 29033864
TI  - Novel Measures to Assess the Effects of Partial Sleep Deprivation on Sensory,
      Working, and Permanent Memory.
AB  - Sleepiness has repeatedly been demonstrated to affect performance on a variety of
      cognitive tasks. While the effects of total sleep deprivation (TSD) have been
      extensively studied, acute partial sleep deprivation (PSD), a more frequent form
      of sleep loss, has been studied much less often. The present study examined the
      effects of sleep deprivation on novel tasks involving classic sensory, working,
      and permanent memory systems. While the tasks did implicate different memory
      systems, they shared a need for effortful, sustained attention to maintain
      successful performance. Because of the novelty of the tasks, an initial study of
      the effects of TSD was carried out. The effects of PSD were subsequently examined
      in a second study, in which subjects were permitted only 4 h of sleep. A general
      detrimental effect of both total and PSD on accuracy of detection was observed
      and to a lesser extent, a slowing of the speed of responding on the different
      tasks. This overall effect is best explained by the often-reported inability to
      sustain attention following sleep loss. Specific effects on distinct cognitive
      processes were also observed, and these were more apparent following total than
      PSD.

PMID- 29033865
TI  - The Holistic Processing Account of Visual Expertise in Medical Image Perception:
      A Review.
AB  - In the field of medical image perception, the holistic processing perspective
      contends that experts can rapidly extract global information about the image,
      which can be used to guide their subsequent search of the image (Swensson, 1980;
      Nodine and Kundel, 1987; Kundel et al., 2007). In this review, we discuss the
      empirical evidence supporting three different predictions that can be derived
      from the holistic processing perspective: Expertise in medical image perception
      is domain-specific, experts use parafoveal and/or peripheral vision to process
      large regions of the image in parallel, and experts benefit from a rapid initial
      glimpse of an image. In addition, we discuss a pivotal recent study (Litchfield
      and Donovan, 2016) that seems to contradict the assumption that experts benefit
      from a rapid initial glimpse of the image. To reconcile this finding with the
      existing literature, we suggest that global processing may serve multiple
      functions that extend beyond the initial glimpse of the image. Finally, we
      discuss future research directions, and we highlight the connections between the
      holistic processing account and similar theoretical perspectives and findings
      from other domains of visual expertise.

PMID- 29033867
TI  - Sweeping the Floor or Putting a Man on the Moon: How to Define and Measure
      Meaningful Work.
AB  - Meaningful work is integral to well-being and a flourishing life. The construct
      of "meaningful work" is, however, consistently affected by conceptual ambiguity.
      Although there is substantial support for arguments to maintain the status of
      conceptual ambiguity, we make a case for the benefits of having consensus on a
      definition and scale of meaningful work in the context of paid work. The
      objective of this article, therefore, was twofold. Firstly, we wanted to develop
      a more integrative definition of meaningful work. Secondly, we wanted to
      establish a corresponding operationalization. We reviewed the literature on the
      existing definitions of meaningful work and the scales designed to measure it. We
      found 14 definitions of meaningful work. Based on these definitions, we
      identified four categories of definitions, which led us to propose an integrative
      and comprehensive definition of meaningful work. We identified two validated
      scales that were partly aligned with the proposed definition. Based on our
      review, we conclude that scholars in this field should coalesce rather than
      diverge their efforts to conceptualize and measure meaningful work.

PMID- 29033866
TI  - Neural Substrate of Group Mental Health: Insights from Multi-Brain Reference
      Frame in Functional Neuroimaging.
AB  - Contemporary mental health practice primarily centers around the neurobiological
      and psychological processes at the individual level. However, a more careful
      consideration of interpersonal and other group-level attributes (e.g.,
      interpersonal relationship, mutual trust/hostility, interdependence, and
      cooperation) and a better grasp of their pathology can add a crucial dimension to
      our understanding of mental health problems. A few recent studies have delved
      into the interpersonal behavioral processes in the context of different
      psychiatric abnormalities. Neuroimaging can supplement these approaches by
      providing insight into the neurobiology of interpersonal functioning. Keeping
      this view in mind, we discuss a recently developed approach in functional
      neuroimaging that calls for a shift from a focus on neural information contained
      within brain space to a multi-brain framework exploring degree of
      similarity/dissimilarity of neural signals between multiple interacting brains.
      We hypothesize novel applications of quantitative neuroimaging markers like inter
      subject correlation that might be able to evaluate the role of interpersonal
      attributes affecting an individual or a group. Empirical evidences of the usage
      of these markers in understanding the neurobiology of social interactions are
      provided to argue for their application in future mental health research.

PMID- 29033869
TI  - Bilinguals' Plausibility Judgments for Phrases with a Literal vs. Non-literal
      Meaning: The Influence of Language Brokering Experience.
AB  - Previous work has shown that prior experience in language brokering (informal
      translation) may facilitate the processing of meaning within and across language
      boundaries. The present investigation examined the influence of brokering on
      bilinguals' processing of two word collocations with either a literal or a
      figurative meaning in each language. Proficient Spanish-English bilinguals
      classified as brokers or non-brokers were asked to judge if adjective+noun
      phrases presented in each language made sense or not. Phrases with a literal
      meaning (e.g., stinging insect) were interspersed with phrases with a figurative
      meaning (e.g., stinging insult) and non-sensical phrases (e.g., stinging picnic).
      It was hypothesized that plausibility judgments would be facilitated for literal
      relative to figurative meanings in each language but that experience in language
      brokering would be associated with a more equivalent pattern of responding across
      languages. These predictions were confirmed. The findings add to the body of
      empirical work on individual differences in language processing in bilinguals
      associated with prior language brokering experience.

PMID- 29033870
TI  - Motivational Objects in Natural Scenes (MONS): A Database of >800 Objects.
AB  - In daily life, we are surrounded by objects with pre-existing motivational
      associations. However, these are rarely controlled for in experiments with
      natural stimuli. Research on natural stimuli would therefore benefit from stimuli
      with well-defined motivational properties; in turn, such stimuli also open new
      paths in research on motivation. Here we introduce a database of Motivational
      Objects in Natural Scenes (MONS). The database consists of 107 scenes. Each scene
      contains 2 to 7 objects placed at approximately equal distance from the scene
      center. Each scene was photographed creating 3 versions, with one object
      ("critical object") being replaced to vary the overall motivational value of the
      scene (appetitive, aversive, and neutral), while maintaining high visual
      similarity between the three versions. Ratings on motivation, valence, arousal
      and recognizability were obtained using internet-based questionnaires. Since the
      main objective was to provide stimuli of well-defined motivational value, three
      motivation scales were used: (1) Desire to own the object; (2) Approach/Avoid;
      (3) Desire to interact with the object. Three sets of ratings were obtained in
      independent sets of observers: for all 805 objects presented on a neutral
      background, for 321 critical objects presented in their scene context, and for
      the entire scenes. On the basis of the motivational ratings, objects were
      subdivided into aversive, neutral, and appetitive categories. The MONS database
      will provide a standardized basis for future studies on motivational value under
      realistic conditions.

PMID- 29033871
TI  - Sense of Place, Fast and Slow: The Potential Contributions of Affordance Theory
      to Sense of Place.
AB  - Over the past 40 years, the sense of place concept has been well-established
      across a range of applications and settings; however, most theoretical
      developments have "privileged the slow." Evidence suggests that place attachments
      and place meanings are slow to evolve, sometimes not matching material or social
      reality (lag effects), and also tending to inhibit change. Here, we present some
      key blind spots in sense of place scholarship and then suggest how a
      reconsideration of sense of place as "fast" and "slow" could fill them. By this,
      we mean how direct and immediate perception-action processes presented in
      affordance theory (resulting in immediately perceived place meanings) can
      complement slower forms of social construction presented in sense of place
      scholarship. Key blind spots are that sense of place scholarship: (1) rarely
      accounts for sensory or immediately perceived meanings; (2) pays little attention
      to how place meanings are the joint product of attributes of environmental
      features and the attributes of the individual; and (3) assumes that the
      relationship between place attachment and behavior is linear and not constituted
      in dynamic relations among mind, culture, and environment. We show how these
      blind spots can begin to be addressed by reviewing key insights from affordance
      theory, and through the presentation of applied examples. We discuss future
      empirical research directions in terms of: (1) how sense of place is both
      perceived and socially constructed; (2) whether perceived and socially
      constructed dimensions of place can relate to one another when perceived meanings
      become unsituated; and (3) how place attachment may change over different stages
      of the life course based upon dynamic relationships between processes of
      perception-action and social construction. We conclude with insights into how
      processes of perception-action and social construction could be included in the
      design and management of urban landscapes.

PMID- 29033868
TI  - Is Schizophrenia a Disorder of Consciousness? Experimental and Phenomenological
      Support for Anomalous Unconscious Processing.
AB  - Decades ago, several authors have proposed that disorders in automatic processing
      lead to intrusive symptoms or abnormal contents in the consciousness of people
      with schizophrenia. However, since then, studies have mainly highlighted
      difficulties in patients' conscious experiencing and processing but rarely
      explored how unconscious and conscious mechanisms may interact in producing this
      experience. We report three lines of research, focusing on the processing of
      spatial frequencies, unpleasant information, and time-event structure that
      suggest that impairments occur at both the unconscious and conscious level. We
      argue that focusing on unconscious, physiological and automatic processing of
      information in patients, while contrasting that processing with conscious
      processing, is a first required step before understanding how distortions or
      other impairments emerge at the conscious level. We then indicate that the
      phenomenological tradition of psychiatry supports a similar claim and provides a
      theoretical framework helping to understand the relationship between the
      impairments and clinical symptoms. We base our argument on the presence of
      disorders in the minimal self in patients with schizophrenia. The minimal self is
      tacit and non-verbal and refers to the sense of bodily presence. We argue this
      sense is shaped by unconscious processes, whose alteration may thus affect the
      feeling of being a unique individual. This justifies a focus on unconscious
      mechanisms and a distinction from those associated with consciousness.

PMID- 29033872
TI  - Theory of Self- vs. Externally-Regulated LearningTM: Fundamentals, Evidence, and
      Applicability.
AB  - The Theory of Self- vs. Externally-Regulated LearningTM has integrated the
      variables of SRL theory, the DEDEPRO model, and the 3P model. This new Theory has
      proposed: (a) in general, the importance of the cyclical model of individual self
      regulation (SR) and of external regulation stemming from the context (ER), as two
      different and complementary variables, both in combination and in interaction;
      (b) specifically, in the teaching-learning context, the relevance of different
      types of combinations between levels of self-regulation (SR) and of external
      regulation (ER) in the prediction of self-regulated learning (SRL), and of
      cognitive-emotional achievement. This review analyzes the assumptions, conceptual
      elements, empirical evidence, benefits and limitations of SRL vs. ERL Theory.
      Finally, professional fields of application and future lines of research are
      suggested.

PMID- 29033873
TI  - A Three-Dimensional Model of Women's Empowerment: Implications in the Field of
      Microfinance and Future Directions.
AB  - Women's empowerment is an important goal in achieving sustainable development
      worldwide. Offering access to microfinance services to women is one way to
      increase women's empowerment. However, empirical evidence provides mixed results
      with respect to its effectiveness. We reviewed previous research on the impact of
      microfinance services on different aspects of women's empowerment. We propose a
      Three-Dimensional Model of Women's Empowerment to integrate previous findings and
      to gain a deeper understanding of women's empowerment in the field of
      microfinance services. This model proposes that women's empowerment can take
      place on three distinct dimensions: (1) the micro-level, referring to an
      individuals' personal beliefs as well as actions, where personal empowerment can
      be observed (2) the meso-level, referring to beliefs as well as actions in
      relation to relevant others, where relational empowerment can be observed and (3)
      the macro-level, referring to outcomes in the broader, societal context where
      societal empowerment can be observed. Importantly, we propose that time and
      culture are important factors that influence women's empowerment. We suggest that
      the time lag between an intervention and its evaluation may influence when
      empowerment effects on the different dimensions occur and that the type of
      intervention influences the sequence in which the three dimensions can be
      observed. We suggest that cultures may differ with respect to which components of
      empowerment are considered indicators of empowerment and how women's position in
      society may influence the development of women's empowerment. We propose that a
      Three-Dimensional Model of Women's Empowerment should guide future programs in
      designing, implementing, and evaluating their interventions. As such our analysis
      offers two main practical implications. First, based on the model we suggest that
      future research should differentiate between the three dimensions of women's
      empowerment to increase our understanding of women's empowerment and to
      facilitate comparisons of results across studies and cultures. Second, we suggest
      that program designers should specify how an intervention should stimulate which
      dimension(s) of women's empowerment. We hope that this model inspires
      longitudinal and cross-cultural research to examine the development of women's
      empowerment on the personal, relational, and societal dimension.

PMID- 29033875
TI  - "I WILL SURVIVE" A Construct Validation Study on the Measurement of Sustainable
      Employability Using Different Age Conceptualizations.
AB  - Though the importance of sustainable employability throughout people's working
      life is undisputed, up till now only one attempt for a conceptual definition has
      been made (van der Klink et al., 2016). Following the suggestions to further
      refine and improve this definition recently put forward by Fleuren et al. (2016),
      we propose an approach to sustainable employability that is based on the Ability
      Motivation-Opportunity (AMO) framework, and incorporates three indicators: the
      ability, the motivation, and the opportunity to continue working, respectively.
      As sustainable employability is considered to be an important aspect of
      successful aging at work, this study used four different conceptualizations of
      aging at work to set up convergent and divergent validity of our
      operationalization of sustainable employability: calendar age, organizational age
      (job and organizational tenure), functional age (work ability), and life-span age
      (partner and children). We formulated several hypotheses that were tested by
      analyzing data from an online survey among 180 employees from Dutch public
      service organizations who filled out a questionnaire on different age concepts,
      and their ability, motivation, and opportunity to continue working. Multiple
      regression analyses were performed, and results showed that the four
      conceptualizations of aging were differently related to the three indicators of
      sustainable employability. Life-span age, in terms of having children, had the
      strongest negative relationship with the ability to continue working,
      organizational age (i.e., organizational tenure) had the strongest negative
      relationship with the motivation to continue working, and functional age had the
      strongest negative relationship with the opportunity to continue working.
      Moreover, functional age was significantly negatively related to the other two
      indicators of sustainable employability too, while life-span age appeared to
      enhance the ability and motivation to continue working (in terms of having
      children) and the perceived opportunity to continue working (in terms of having a
      partner). Calendar age was only important for the opportunity to continue working
      and appeared to have a negative association with this outcome variable. These
      results lend support to our proposed operationalization of sustainable
      employability by showing that the three indicators are differently related to
      different age conceptualizations thus expanding previous research on the
      conceptualization of sustainable employability.

PMID- 29033874
TI  - Testing the Motor Simulation Account of Source Errors for Actions in Recall.
AB  - Observing someone else perform an action can lead to false memories of self
      performance - the observation inflation effect. One explanation is that action
      simulation via mirror neuron activation during action observation is responsible
      for observation inflation by enriching memories of observed actions with motor
      representations. In three experiments we investigated this account of source
      memory failures, using a novel paradigm that minimized influences of
      verbalization and prior object knowledge. Participants worked in pairs to take
      turns acting out geometric shapes and letters. The next day, participants
      recalled either actions they had performed or those they had observed. Experiment
      1 showed that participants falsely retrieved observed actions as self-performed,
      but also retrieved self-performed actions as observed. Experiment 2 showed that
      preventing participants from encoding observed actions motorically by taxing
      their motor system with a concurrent motor task did not lead to the predicted
      decrease in false claims of self-performance. Indeed, Experiment 3 showed that
      this was the case even if participants were asked to carefully monitor their
      recall. Because our data provide no evidence for a motor activation account, we
      also discussed our results in light of a source monitoring account.

PMID- 29033876
TI  - Ideal Standards, Acceptance, and Relationship Satisfaction: Latitudes of
      Differential Effects.
AB  - We examined whether the relations of consistency between ideal standards and
      perceptions of a current romantic partner with partner acceptance and
      relationship satisfaction level off, or decelerate, above a threshold. We tested
      our hypothesis using a 3-year longitudinal data set collected from heterosexual
      newlywed couples. We used two indicators of consistency: pattern correspondence
      (within-person correlation between ideal standards and perceived partner ratings)
      and mean-level match (difference between ideal standards score and perceived
      partner score). Our results revealed that pattern correspondence had no relation
      with partner acceptance, but a positive linear/exponential association with
      relationship satisfaction. Mean-level match had a significant positive
      association with actor's acceptance and relationship satisfaction up to the point
      where perceived partner score equaled ideal standards score. Partner effects did
      not show a consistent pattern. The results suggest that the consistency between
      ideal standards and perceived partner attributes has a non-linear association
      with acceptance and relationship satisfaction, although the results were more
      conclusive for mean-level match.

PMID- 29033877
TI  - Music Interventions and Child Development: A Critical Review and Further
      Directions.
AB  - Research on the impact of music interventions has indicated positive effects on a
      variety of skills. These findings suggest musical interventions may have further
      potential to support educational processes and development of children. This
      paper reviews the latest evidence on the effect of musical interventions on the
      development of primary school-aged children. Four electronic databases were
      searched from January 2010 through June 2016 using music, music instruction,
      music education, music lesson, music training, development, child, student, and
      pupil as key words for the search. Two reviewers independently evaluated the
      studies to determine whether they met the stated inclusion criteria. Studies were
      compared on study setup, methodological quality, intervention components, outcome
      variables, and efficacy. A review of these selected studies (n = 46) suggestive
      beneficial effects of music intervention on development of children, although
      clear conclusions cannot be drawn. Possible influencing factors that might
      contribute to the outcome of intervention are reviewed and recommendations for
      further research are made.

PMID- 29033879
TI  - Nasally-Administered Oxytocin Has Limited Effects on Owner-Directed Attachment
      Behavior in Pet Dogs (Canis lupus familiaris).
AB  - The present study explored the effects of intranasal oxytocin, a naturally
      occurring hormone, on the behavior of pet dogs during an attachment test. Each
      dog participated in two testing sessions. On one visit saline was administered
      nasally, and on another, oxytocin was administered nasally. For half of the dogs
      (n = 20), solutions were administered with a Mucosal Atomization Device (MAD) and
      for half of the dogs (n = 20), solutions were administered using a nasal spray
      bottle. Condition order was counterbalanced and a double-blind methodology was
      employed. Following a 30-min wait period after administration of solutions, dog
      owner pairs participated in the Secure Base Test, a short attachment test
      consisting of three 2-min phases: (1) Baseline- the owner was present, dogs were
      able to freely explore the testing room (2) Alone- dogs were left alone in the
      testing room (3) Return- owners re-entered the room and were reunited with their
      dog. In each phase the dog was evaluated for contact seeking, exploration, and
      avoidance behaviors. Although, oxytocin administration was expected to increase
      owner-directed proximity and contact seeking behavior, this effect was not
      observed. In fact, in the baseline phase, dogs spent significantly more time
      seeking the proximity of their owners when they received saline than when they
      received OT (p < 0.05). Sex differences were also assessed for the behavioral
      variables of interest in the Secure Base Test, and results indicated that OT did
      not affect dogs' behavior in the alone phase, but when saline was administered,
      females spent significantly more time in contact with the door than males in the
      alone phase (p < 0.05). Overall, the effects of nasally administered oxytocin on
      attachment related behavior appeared to be limited or inconsistent for this pet
      dog population.

PMID- 29033878
TI  - The Actor, Partner, Similarity Effects of Personality, and Interactions with
      Gender and Relationship Duration among Chinese Emerging Adults.
AB  - Understanding personality effects and their role in influencing relationship
      quality, varied according to gender and relationship duration, could help us
      better understand close relationships. Participants were Chinese dating dyads and
      were asked to complete both the Big Five Inventory and Perceived Relationship
      Quality Component scales. Males and those who had a long-term relationship
      perceived better relationship quality; individuals who scored higher on
      agreeableness, conscientiousness, openness, and emotional stability enjoyed
      better relationship quality; gender and/or relationship duration moderated the
      actor effect of extraversion and the partner effects of conscientiousness,
      emotional stability, and openness on relationship quality. Regarding the profile
      similarity, those couples who were more dissimilar in their profile personality
      had better relationship quality, especially when they were in a relatively long
      term relationship. Meanwhile, with an increase in profile similarity, the males'
      perceived relationship quality decreased.

PMID- 29033880
TI  - Exploring the Multi-Layered Affordances of Composing and Performing Interactive
      Music with Responsive Technologies.
AB  - The question motivating the work presented here, starting from a view of music as
      embodied and situated activity, is how can we account for the complexity of
      interactive music performance situations. These are situations in which human
      performers interact with responsive technologies, such as sensor-driven
      technology or sound synthesis affected by analysis of the performed sound signal.
      This requires investigating in detail the underlying mechanisms, but also
      providing a more holistic approach that does not lose track of the complex whole
      constituted by the interactions and relationships of composers, performers,
      audience, technologies, etc. The concept of affordances has frequently been
      invoked in musical research, which has seen a "bodily turn" in recent years,
      similar to the development of the embodied cognition approach in the cognitive
      sciences. We therefore begin by broadly delineating its usage in the cognitive
      sciences in general, and in music research in particular. We argue that what is
      still missing in the discourse on musical affordances is an encompassing
      theoretical framework incorporating the sociocultural dimensions that are
      fundamental to the situatedness and embodiment of interactive music performance
      and composition. We further argue that the cultural affordances framework,
      proposed by Rietveld and Kiverstein (2014) and recently articulated further by
      Ramstead et al. (2016) in this journal, although not previously applied to music,
      constitutes a promising starting point. It captures and elucidates this complex
      web of relationships in terms of shared landscapes and individual fields of
      affordances. We illustrate this with examples foremost from the first author's
      artistic work as composer and performer of interactive music. This sheds new
      light on musical composition as a process of construction-and embodied mental
      simulation-of situations, guiding the performers' and audience's attention in
      shifting fields of affordances. More generally, we believe that the theoretical
      perspectives and concrete examples discussed in this paper help to elucidate how
      situations-and with them affordances-are dynamically constructed through the
      interactions of various mechanisms as people engage in embodied and situated
      activity.

PMID- 29033881
TI  - Age and Gender Differences in Facial Attractiveness, but Not Emotion Resemblance,
      Contribute to Age and Gender Stereotypes.
AB  - Considerable research has shown effects of facial appearance on trait impressions
      and group stereotypes. We extended those findings in two studies that
      investigated the contribution of resemblance to emotion expressions and
      attractiveness to younger adults (YA) and older adults (OA) age and gender
      stereotypes on the dimensions of warmth and competence. Using connectionist
      modeling of facial metrics of 240 neutral younger and older faces, Study 1 found
      that, neutral expression older faces or female faces showed greater structural
      resemblance to happy expressions and less resemblance to angry expressions than
      did younger or male faces, respectively. In addition, neutral female faces showed
      greater resemblance to surprise expressions. In Study 2, YA and OA rated the
      faces of Study 1 for attractiveness and for 4 traits that we aggregated on the
      dimensions of competence (competent, healthy) and warmth (trustworthy, not
      shrewd). We found that YA, but not OA, age stereotypes replicated previous
      research showing higher perceived warmth and lower perceived competence in older
      adults. In addition, previously documented gender stereotypes were moderated by
      face age for both YA and OA. The greater attractiveness of younger than older
      faces and female than male faces influenced age and gender stereotypes, including
      these deviations from prior research findings using category labels rather than
      faces. On the other hand, face age and face sex differences in emotion
      resemblance did not influence age or gender stereotypes, contrary to prediction.
      Our results provide a caveat to conclusions about age and gender stereotypes
      derived from responses to category labels, and they reveal the importance of
      assessing stereotypes with a methodology that is sensitive to influences of group
      differences in appearance that can exacerbate or mitigate stereotypes in more
      ecologically valid contexts. Although the gender differences in attractiveness in
      the present study may not have generalizability, the age differences likely do,
      and the fact that they can weaken the attribution of greater warmth and
      strengthen the attribution of lower competence to older than younger individuals
      has important practical implications.

PMID- 29033882
TI  - Commentary: The effects of acute stress on core executive functions: A meta
      analysis and comparison with cortisol.

PMID- 29033883
TI  - Figurative Language, Language Disorders, and Language(s) Evolution.

PMID- 29033884
TI  - Commentary: Psychological Science's Aversion to the Null.

PMID- 29033886
TI  - Complex Problem Solving in Teams: The Impact of Collective Orientation on Team
      Process Demands.
AB  - Complex problem solving is challenging and a high-level cognitive process for
      individuals. When analyzing complex problem solving in teams, an additional, new
      dimension has to be considered, as teamwork processes increase the requirements
      already put on individual team members. After introducing an idealized teamwork
      process model, that complex problem solving teams pass through, and integrating
      the relevant teamwork skills for interdependently working teams into the model
      and combining it with the four kinds of team processes (transition, action,
      interpersonal, and learning processes), the paper demonstrates the importance of
      fulfilling team process demands for successful complex problem solving within
      teams. Therefore, results from a controlled team study within complex situations
      are presented. The study focused on factors that influence action processes, like
      coordination, such as emergent states like collective orientation, cohesion, and
      trust and that dynamically enable effective teamwork in complex situations.
      Before conducting the experiments, participants were divided by median split into
      two-person teams with either high (n = 58) or low (n = 58) collective orientation
      values. The study was conducted with the microworld C3Fire, simulating dynamic
      decision making, and acting in complex situations within a teamwork context. The
      microworld includes interdependent tasks such as extinguishing forest fires or
      protecting houses. Two firefighting scenarios had been developed, which takes a
      maximum of 15 min each. All teams worked on these two scenarios. Coordination
      within the team and the resulting team performance were calculated based on a log
      file analysis. The results show that no relationships between trust and action
      processes and team performance exist. Likewise, no relationships were found for
      cohesion. Only collective orientation of team members positively influences team
      performance in complex environments mediated by action processes such as
      coordination within the team. The results are discussed in relation to previous
      empirical findings and to learning processes within the team with a focus on
      feedback strategies.

PMID- 29033885
TI  - Emotions and Steroid Secretion in Aging Men: A Multi-Study Report.
AB  - Although aging increases the risk of cognitive and socioemotional deterioration,
      it has also been shown to be accompanied by an increase in experienced positive
      emotions and a decrease in negative emotions. Steroid hormones and age-related
      alterations in secretion patterns have been suggested to play a crucial role in
      these age-related changes in emotional experience. Importantly, previous studies
      identified effects of neuroactive hormones on age-related alterations in
      emotional experience, which vary by sex and depression levels. Therefore, in
      three independent cross-sectional studies including a total of 776 men, we
      examined age-related differences in emotional experience and subsequently the
      moderation effect of steroid hormones. Sample one consisted of 271 self-reporting
      healthy (SRH) men aged between 40 and 75 years, while sample two comprised 121
      men in the identical age range but only including vitally exhausted (VE) men.
      Sample three included 384 men aged between 25 and 78 years who reported having
      fathered (FA) at least one child. For the SRH men, age was negatively associated
      with anxiety symptoms and aggression, while negative trends emerged for
      depressive symptoms. In VE men, age was negatively associated with depressive
      symptoms and positively associated with aggression and positive emotions. For FA
      men, anxiety symptoms and aggression were negatively associated with age. Age
      trends of steroid hormones and identified moderation effects are reported.
      However, with adjustment for multiple comparisons, most of the significant
      associations fade and the reported associations need to be regarded as
      exploratory starting points for the further investigation of age-related
      alterations in emotional experience and their relation to steroid secretion.
      Overall, the results indicate that salivary cortisol might be a moderator of the
      association between age and symptoms of anxiety for SRH and VE men, while
      salivary testosterone seems to moderate the association between age and symptoms
      of anxiety or depression in VE and FA men, respectively. Both hair cortisol and
      progesterone seem to influence age-related alterations in anger experience. Age
      related alterations in the hypothalamic-pituitary-adrenal (HPA) axis and the
      hypothalamic-pituitary-gonadal (HPG) axis emerge as promising avenues to further
      investigate the decrease in experienced negative emotions in aging men.

PMID- 29033887
TI  - Atypical Cerebral Manifestations of Disseminated Mycobacterium tuberculosis.
AB  - BACKGROUND: We investigated the patterns of cerebral manifestations in patients
      with underlying pulmonary or extrapulmonary tuberculosis or disseminated
      tuberculosis. MATERIALS AND METHODS: From January 2010 to September 2016, brain
      magnetic resonance imaging (MRI) scans were obtained to evaluate cerebral
      manifestations in patients with underlying pulmonary or extrapulmonary
      tuberculosis. We also included patients with drug-resistant tuberculosis or
      disseminated tuberculosis. MRI findings of tuberculous meningitis and tuberculoma
      were classified as typical; other MRI findings were classified as atypical.
      Demographic data, risk factors, and drug regimens were collected and analyzed.
      RESULTS: Twenty-two patients were diagnosed with cerebral tuberculosis. Cerebral
      tuberculosis was due to hematogenous spread from pulmonary tuberculosis (10
      patients), spinal tuberculosis (8 patients), disseminated tuberculosis (3
      patients), and unknown causes (1 patient). There were six patients with typical
      MRI findings (three patients with typical meningitis involving the basal cistern
      and supratentorium, one patient with tuberculomas, and two patients with both)
      and seven patients with atypical MRI findings [five patients with evidence of
      early meningitis, such as high signal intensity on fluid-attenuated inversion
      recovery (FLAIR) along the cerebellar folia, and two patients with only
      hydrocephalus]. CONCLUSION: Besides the typical sites of meningeal involvement,
      overlooked findings such as FLAIR abnormalities along the cerebellar folia or
      hydrocephalus should be checked for early detection of cerebral tuberculosis and
      initiation of the appropriate treatment against disseminated tuberculosis.

PMID- 29033889
TI  - A Retrospective Study of the Characteristics and Clinical Significance of A-Waves
      in Amyotrophic Lateral Sclerosis.
AB  - A-wave was observed in patients with motor neuron disease (1). However, data on
      the characteristics and clinical significance of A-waves in patients with
      amyotrophic lateral sclerosis (ALS) have been scarce. The F-wave studies of 83
      patients with ALS and 63 normal participants which were conducted previously at
      the Department of Neurology in Peking Union Medical College Hospital were
      retrospectively reviewed to determine the occurrence of A-waves in ALS. A-waves
      occurred more frequently in ALS patients than in normal controls. For the median
      and peroneal nerves, the frequencies of nerves with A-waves and frequencies of
      patients with A-waves were comparable between the ALS patients and normal
      controls. For the ulnar and tibial nerves, the frequencies of nerves with A-waves
      and frequencies of patients with A-waves were significantly increased in the ALS
      patients compared with those of the normal participants. Disease progression rate
      was slower in the ALS patients with A-waves (0.73 +/- 0.99) than that in the ALS
      patients without A-waves (0.87 +/- 0.55, P = 0.007). No correlations were found
      between the amplitudes of F-waves with A-waves and those of A-waves in the ulnar
      nerves (r = 0.423, P = 0.149). No correlations were found between the persistence
      of F-waves with A-waves and the persistence of A-waves in the ulnar nerves as
      well (r = 0.219, P = 0.473). The occurrence of A-waves may indicate dysfunction
      of lower motor neurons and possibly imply a relatively slower degenerative
      process.

PMID- 29033891
TI  - Commentary: The Effect of Systemic Nitroglycerin Administration on the Kynurenine
      Pathway in the Rat.

PMID- 29033890
TI  - An Enigmatic Case of Acute Mercury Poisoning: Clinical, Immunological Findings
      and Platelet Function.
AB  - Severe mercury intoxication is very rare in developed countries, but still occurs
      as the result of volatile substance abuse, suicide attempts, occupational
      hazards, or endemic food ingestion as reported in the cases of public health
      disasters in Iraq and in Minamata Bay, Japan. Here, we describe the dramatic
      physical and cognitive decline of a 23-year-old patient caused by a severe methyl
      mercury (MeHg) intoxication of unknown origin. We show serial magnetic resonance
      imaging (MRI) of the patient's brain, as well as ex vivo analyses of blood and
      cerebrospinal fluid including multicolor flow cytometric measurements, functional
      assays of hemostaseologic efficacy, and evaluation of regulatory effector
      molecules. Together with the clinical history, our findings show the progressive
      neuronal degeneration accompanying the deterioration of the patient. Moreover,
      the ex vivo analyses display alterations of thrombocyte function and coagulation,
      as well as an immunological milieu facilitating autoimmunity. Despite the
      successful reduction of the MeHg concentration in the patient's blood with
      erythrocyte apheresis and chelator therapy, his condition did not improve and led
      to a persistent vegetative state. This case illustrates the neurotoxicity of MeHg
      following severe intoxication for the first time by serial MRI. Data on immune
      cell and thrombocyte function as well as on coagulation in mercury poisoning
      reveal potential implications for anticoagulation and immunomodulatory treatment.

PMID- 29033892
TI  - Molecular Diagnosis of Myoclonus Epilepsy Associated with Ragged-Red Fibers
      Syndrome in the Absence of Ragged Red Fibers.
AB  - Myoclonus epilepsy with ragged-red fibers (MERRFs), an inherited mitochondrial
      disorder, has characteristic morphological changes of ragged-red fibers (RRFs) in
      muscle biopsy, in the absence of which mitochondrial etiology is usually not
      considered in patients with phenotypes suggestive of MERRF. In these
      circumstances, MERRF can only be diagnosed using genetic analyses. The symptoms,
      pathological findings, and imaging results being age dependent, we can construct
      a protocol based on these characteristics to understand the disease's natural
      course and to manage patients more effectively. The absence of RRFs should not
      preclude a MERRF diagnosis.

PMID- 29033888
TI  - Concussion As a Multi-Scale Complex System: An Interdisciplinary Synthesis of
      Current Knowledge.
AB  - Traumatic brain injury (TBI) has been called "the most complicated disease of the
      most complex organ of the body" and is an increasingly high-profile public health
      issue. Many patients report long-term impairments following even "mild" injuries,
      but reliable criteria for diagnosis and prognosis are lacking. Every clinical
      trial for TBI treatment to date has failed to demonstrate reliable and safe
      improvement in outcomes, and the existing body of literature is insufficient to
      support the creation of a new classification system. Concussion, or mild TBI, is
      a highly heterogeneous phenomenon, and numerous factors interact dynamically to
      influence an individual's recovery trajectory. Many of the obstacles faced in
      research and clinical practice related to TBI and concussion, including observed
      heterogeneity, arguably stem from the complexity of the condition itself. To
      improve understanding of this complexity, we review the current state of research
      through the lens provided by the interdisciplinary field of systems science,
      which has been increasingly applied to biomedical issues. The review was
      conducted iteratively, through multiple phases of literature review, expert
      interviews, and systems diagramming and represents the first phase in an effort
      to develop systems models of concussion. The primary focus of this work was to
      examine concepts and ways of thinking about concussion that currently impede
      research design and block advancements in care of TBI. Results are presented in
      the form of a multi-scale conceptual framework intended to synthesize knowledge
      across disciplines, improve research design, and provide a broader, multi-scale
      model for understanding concussion pathophysiology, classification, and
      treatment.

PMID- 29033894
TI  - Serum Thyrotropin and Phase of the Menstrual Cycle.
AB  - About one-fifth of patients treated with levothyroxine have serum thyrotropin
      (TSH) above target concentrations but, in approximately 15% of them, the cause of
      this TSH insufficient normalization remains unknown. We report the cases of two
      regularly menstruating women with known thyroid disease who had TSH levels
      consistently >3 mU/L (and sometimes above target levels) during mid-cycle, but
      consistently lower serum levels during the follicular and luteal phases of
      menstrual cycle. A major TSH release by the thyrotrophs in response to high
      circulating levels of estradiol (E2) at mid-cycle may increase levels of TSH
      compared to other phases of the cycle. The increased TSH can be misinterpreted as
      refractory hypothyroidism if the woman is under L-T4 replacement therapy or as
      subclinical hypothyroidism if the woman is not. Our findings might have important
      implications for diagnosis and management of thyroid disease, suggesting to
      request serum TSH measurements outside of the periovulatory days.

PMID- 29033893
TI  - Shortcomings in the Current Amyotrophic Lateral Sclerosis Trials and Potential
      Solutions for Improvement.
AB  - Amyotrophic lateral sclerosis (ALS) is a clinically progressive neurodegenerative
      syndrome predominantly affecting motor neurons and their associated tracts.
      Riluzole and edaravone are the only FDA certified drugs for treating ALS. Over
      the past two decades, almost all clinical trials aiming to develop a successful
      therapeutic strategy for this disease have failed. Genetic complexity, inadequate
      animal models, poor clinical trial design, lack of sensitive biomarkers, and
      diagnostic delays are some of the potential reasons limiting any significant
      development in ALS clinical trials. In this review, we have outlined the possible
      reasons for failure of ALS clinical trials, addressed the factors limiting timely
      diagnosis, and suggested possible solutions for future considerations for each of
      the shortcomings.

PMID- 29033895
TI  - Autoimmune Thyroid Diseases in Patients Treated with Alemtuzumab for Multiple
      Sclerosis: An Example of Selective Anti-TSH-Receptor Immune Response.
AB  - Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is approved for the
      treatment of active relapsing-remitting multiple sclerosis (MS). Alemtuzumab
      induces a rapid and prolonged depletion of lymphocytes from the circulation,
      which results in a profound immuno-suppression status followed by an immune
      reconstitution phase. Secondary to reconstitution autoimmune diseases represent
      the most common side effect of Alemtuzumab treatment. Among them, Graves' disease
      (GD) is the most frequent one with an estimated prevalence ranging from 16.7 to
      41.0% of MS patients receiving Alemtuzumab. Thyrotropin (TSH) receptor (R)
      reactive B cells are typically observed in GD and eventually present this
      autoantigen to T-cells, which, in turn, secrete several pro-inflammatory
      cytokines and chemokines. Given that reconstitution autoimmunity is more
      frequently characterized by autoantibody-mediated diseases rather than by
      destructive Th1-mediated disorders, it is not surprising that GD is the most
      commonly reported side effect of Alemtuzumab treatment in patients with MS. On
      the other hand, immune reconstitution GD was not observed in a large series of
      patients with rheumatoid arthritis treated with Alemtuzumab. This negative
      finding supports the view that patients with MS are intrinsically more at risk
      for developing Alemtuzumab-related thyroid dysfunctions and in particular of GD.
      From a clinical point of view, Alemtuzumab-induced GD is characterized by a
      surprisingly high rate of remission, both spontaneous and after antithyroid
      drugs, as well as by a spontaneous shift to hypothyroidism, which is supposed to
      result from a change from stimulating to blocking TSH-receptor antibodies. These
      immune and clinical peculiarities support the concept that antithyroid drugs
      should be the first-line treatment in Alemtuzumab-induced Graves'
      hyperthyroidism.

PMID- 29033896
TI  - The Influence of a KDT501, a Novel Isohumulone, on Adipocyte Function in Humans.
AB  - OBJECTIVE: In a phase II clinical trial in nine obese, insulin-resistant humans,
      we observed that treatment with KDT501, a novel isohumulone drug, increased total
      and high-molecular weight (HMW) adiponectin in plasma. The objective was to
      determine whether KDT501 increased adiponectin secretion from subcutaneous white
      adipose tissue (SC WAT) and the underlying mechanism(s). METHODS: Nine obese
      participants with either prediabetes or with normal glucose tolerance plus three
      features of metabolic syndrome were part of the study. SC WAT biopsies were
      performed before and after 28 days of KDT501 treatment in a clinical research
      setting. In addition, a cold stimulus was used to induce thermogenic gene
      expression. Adiponectin secretion was measured, and gene expression of 130 genes
      involved in adipose tissue function was determined. The effect of KDT501 on
      adipocyte mitochondrial function was analyzed in vitro. RESULTS: SC WAT explants
      secreted more total and HMW adiponectin after KDT501 treatment (P < 0.05). After
      KDT501 treatment, a number of genes involved in thermogenesis and lipolysis were
      induced by cold (P < 0.05). KDT501 also potentiated beta-adrenergic signaling (P
      < 0.001) and enhanced mitochondrial function in adipocytes (P < 0.001).
      CONCLUSION: KDT501 induced adiponectin secretion posttranscriptionally and
      increased gene expression of thermogenic and lipolytic genes in response to cold
      stimulation. These beneficial effects on SC WAT may be explained by the ability
      of KDT501 to potentiate beta-adrenergic signaling and enhance mitochondrial
      function in adipocytes. CLINICAL TRIAL REGISTRATION:
      https://www.ClinicalTrials.gov, ID number: NCT02444910.

PMID- 29033897
TI  - Evaluation of Cardiometabolic Parameters among Obese Women Using Oral
      Contraceptives.
AB  - BACKGROUND: Combined oral contraceptive (COC) use has been associated with an
      unfavorable impact on carbohydrate and lipid metabolism in diverse populations of
      normal weight and obese women. The present study aimed to evaluate the
      cardiometabolic and inflammatory profiles of women in northeastern Brazil with
      respect to COC use and obesity. METHODS: We performed a cross-sectional study to
      verify cardiovascular parameters, including blood pressure (BP), fasting serum
      glucose, lipid, and inflammatory profile, in a population of women aged 15-45
      years, considering obesity and COC use. Our sample consisted of 591 women, 481
      women who were COC users, and 110 age-matched women who were COC non-users,
      classified as obese and non-obese according to BMI. RESULTS: COC use and obesity
      were associated with increased systolic (p <= 0.001) and diastolic BP (p =
      0.001), blood glucose (p <= 0.001), total cholesterol (p = 0.008), low-density
      lipoprotein cholesterol (p <= 0.001), very low-density lipoprotein cholesterol (p
      <= 0.001), triglycerides (p <= 0.001), ferritin (p = 0.006), C-reactive protein
      (CRP) (p <= 0.001), and nitric oxide metabolites (p <= 0.001), as well as
      decreased high-density lipoprotein cholesterol (HDL-c) (p <= 0.001) in comparison
      to controls. CRP and HDL-c levels in obese COC users were determined to be
      outside reference range values. The odds of having lower levels of HDL-c and
      elevated CRP increased among obese COC users. COC use was independently
      associated with low levels of HDL-c, especially second-generation progestins (p <
      0.001; OR = 8.976; 95% CI 2.786-28.914). CONCLUSION: Obesity and COC use were
      associated with alterations in lipid and inflammatory cardiometabolic parameters,
      particularly increased CRP levels and decreased HDL-c, which are considered
      markers of cardiovascular disease (CVD) risk. Given the need to prevent
      unintended pregnancy among obese women, together with weight loss counseling, it
      is important to evaluate the most effective and safest contraceptive methods to
      avoid the potential risk of developing CVD.

PMID- 29033898
TI  - Functional Characterization of Paralogous Gonadotropin-Releasing Hormone-Type and
      Corazonin-Type Neuropeptides in an Echinoderm.
AB  - Homologs of the vertebrate neuropeptide gonadotropin-releasing hormone (GnRH)
      have been identified in invertebrates, including the insect neuropeptide
      corazonin (CRZ). Recently, we reported the discovery of GnRH-type and CRZ-type
      signaling systems in an echinoderm, the starfish Asterias rubens, demonstrating
      that the evolutionary origin of paralogous GnRH-type and CRZ-type neuropeptides
      can be traced back to the common ancestor of protostomes and deuterostomes. Here,
      we have investigated the physiological roles of the GnRH-type (ArGnRH) and the
      CRZ-type (ArCRZ) neuropeptides in A. rubens, using mRNA in situ hybridization,
      immunohistochemistry and in vitro pharmacology. ArGnRH precursor (ArGnRHP)
      expressing cells and ArGnRH-immunoreactive cells and/or processes are present in
      the radial nerve cords, circumoral nerve ring, digestive system (e.g., cardiac
      stomach and pyloric stomach), body wall-associated muscle (apical muscle), and
      appendages (tube feet, terminal tentacle). The general distribution of ArCRZ
      precursor (ArCRZP)-expressing cells is similar to that of ArGnRHP, but with
      specific local differences. For example, cells expressing ArGnRHP are present in
      both the ectoneural and hyponeural regions of the radial nerve cords and
      circumoral nerve ring, whereas cells expressing ArCRZP were only observed in the
      ectoneural region. In vitro pharmacological experiments revealed that both ArGnRH
      and ArCRZ cause contraction of cardiac stomach, apical muscle, and tube foot
      preparations. However, ArGnRH was more potent/effective than ArCRZ as a
      contractant of the cardiac stomach, whereas ArCRZ was more potent/effective than
      ArGnRH as a contractant of the apical muscle. These findings demonstrate that
      both ArGnRH and ArCRZ are myoexcitatory neuropeptides in starfish, but
      differences in their expression patterns and pharmacological activities are
      indicative of distinct physiological roles. This is the first study to
      investigate the physiological roles of both GnRH-type and CRZ-type neuropeptides
      in a deuterostome, providing new insights into the evolution and comparative
      physiology of these paralogous neuropeptide signaling systems in the Bilateria.

PMID- 29033900
TI  - Weak Organic Acids Decrease Borrelia burgdorferi Cytoplasmic pH, Eliciting an
      Acid Stress Response and Impacting RpoN- and RpoS-Dependent Gene Expression.
AB  - The spirochete Borrelia burgdorferi survives in its tick vector, Ixodes
      scapularis, or within various hosts. To transition between and survive in these
      distinct niches, B. burgdorferi changes its gene expression in response to
      environmental cues, both biochemical and physiological. Exposure of B.
      burgdorferi to weak monocarboxylic organic acids, including those detected in the
      blood meal of fed ticks, decreased the cytoplasmic pH of B. burgdorferi in vitro.
      A decrease in the cytoplasmic pH induced the expression of genes encoding enzymes
      that have been shown to restore pH homeostasis in other bacteria. These include
      putative coupled proton/cation exchangers, a putative Na+/H+ antiporter, a
      neutralizing buffer transporter, an amino acid deaminase and a proton exporting
      vacuolar-type VoV1 ATPase. Data presented in this report suggested that the acid
      stress response triggered the expression of RpoN- and RpoS-dependent genes
      including important virulence factors such as outer surface protein C (OspC),
      BBA66, and some BosR (Borrelia oxidative stress regulator)-dependent genes.
      Because the expression of virulence factors, like OspC, are so tightly connected
      by RpoS to general cellular stress responses and cell physiology, it is difficult
      to separate transmission-promoting conditions in what is clearly a multifactorial
      and complex regulatory web.

PMID- 29033901
TI  - Monte Carlo Simulations Suggest Current Chlortetracycline Drug-Residue Based
      Withdrawal Periods Would Not Control Antimicrobial Resistance Dissemination from
      Feedlot to Slaughterhouse.
AB  - Antimicrobial use in beef cattle can increase antimicrobial resistance prevalence
      in their enteric bacteria, including potential pathogens such as Escherichia
      coli. These bacteria can contaminate animal products at slaughterhouses and cause
      food-borne illness, which can be difficult to treat if it is due to antimicrobial
      resistant bacteria. One potential intervention to reduce the dissemination of
      resistant bacteria from feedlot to consumer is to impose a withdrawal period
      after antimicrobial use, similar to the current withdrawal period designed to
      prevent drug residues in edible animal meat. We investigated tetracycline
      resistance in generic E. coli in the bovine large intestine during and after
      antimicrobial treatment by building a mathematical model of oral
      chlortetracycline pharmacokinetics-pharmacodynamics and E. coli population
      dynamics. We tracked three E. coli subpopulations (susceptible, intermediate, and
      resistant) during and after treatment with each of three United States
      chlortetracycline indications (liver abscess reduction, disease control, disease
      treatment). We compared the proportion of resistant E. coli before antimicrobial
      use to that at several time points after treatment and found a greater proportion
      of resistant enteric E. coli after the current withdrawal periods than prior to
      treatment. In order for the proportion of resistant E. coli in the median beef
      steer to return to the pre-treatment level, withdrawal periods of 15 days after
      liver abscess reduction dosing (70 mg daily), 31 days after disease control
      dosing (350 mg daily), and 36 days after disease treatment dosing (22 mg/kg
      bodyweight for 5 days) are required in this model. These antimicrobial resistance
      withdrawal periods would be substantially longer than the current U.S.
      withdrawals of 0-2 days or Canadian withdrawals of 5-10 days. One published field
      study found similar time periods necessary to reduce the proportion of resistant
      E. coli following chlortetracycline disease treatment to those suggested by this
      model, but additional carefully designed field studies are necessary to confirm
      the model results. This model is limited to biological processes within the
      cattle and does not include resistance selection in the feedlot environment or co
      selection of chlortetracycline resistance following other antimicrobial use.

PMID- 29033902
TI  - Analyzing the Complex Regulatory Landscape of Hfq - an Integrative, Multi-Omics
      Approach.
AB  - The ability of bacteria to respond to environmental change is based on the
      ability to coordinate, redirect and fine-tune their genetic repertoire as and
      when required. While we can learn a great deal from reductive analysis of
      individual pathways and global approaches to gene regulation, a deeper
      understanding of these complex signaling networks requires the simultaneous
      consideration of several regulatory layers at the genome scale. To highlight the
      power of this approach we analyzed the Hfq transcriptional/translational
      regulatory network in the model bacterium Pseudomonas fluorescens. We first used
      extensive 'omics' analyses to assess how hfq deletion affects mRNA abundance,
      mRNA translation and protein abundance. The subsequent, multi-level integration
      of these datasets allows us to highlight the discrete contributions by Hfq to
      gene regulation at different levels. The integrative approach to regulatory
      analysis we describe here has significant potential, for both dissecting
      individual signaling pathways and understanding the strategies bacteria use to
      cope with external challenges.

PMID- 29033899
TI  - Environmental Factors Contribute to beta Cell Endoplasmic Reticulum Stress and
      Neo-Antigen Formation in Type 1 Diabetes.
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which immune-mediated targeting
      and destruction of insulin-producing pancreatic islet beta cells leads to chronic
      hyperglycemia. There are many beta cell proteins that are targeted by
      autoreactive T cells in their native state. However, recent studies have
      demonstrated that many beta cell proteins are recognized as neo-antigens
      following posttranslational modification (PTM). Although modified neo-antigens
      are well-established targets of pathology in other autoimmune diseases, the
      effects of neo-antigens in T1D progression and the mechanisms by which they are
      generated are not well understood. We have demonstrated that PTM occurs during
      endoplasmic reticulum (ER) stress, a process to which beta cells are uniquely
      susceptible due to the high rate of insulin production in response to dynamic
      glucose sensing. In the context of genetic susceptibility to autoimmunity,
      presentation of these modified neo-antigens may activate autoreactive T cells and
      cause pathology. However, inherent beta cell ER stress and protein PTM do not
      cause T1D in every genetically susceptible individual, suggesting the
      contribution of additional factors. Indeed, many environmental factors, such as
      viral infection, chemicals, or inflammatory cytokines, are associated with T1D
      onset, but the mechanisms by which these factors lead to disease onset remain
      unknown. Since these environmental factors also cause ER stress, exposure to
      these factors may enhance production of neo-antigens, therefore boosting beta
      cell recognition by autoreactive T cells and exacerbating T1D pathogenesis.
      Therefore, the combined effects of physiological ER stress and the stress that is
      induced by environmental factors may lead to breaks in peripheral tolerance,
      contribute to antigen spread, and hasten disease onset. This Hypothesis and
      Theory article summarizes what is currently known about ER stress and protein PTM
      in autoimmune diseases including T1D and proposes a role for environmental
      factors in breaking immune tolerance to beta cell antigens through neo-antigen
      formation.

PMID- 29033903
TI  - Protective Effect of Akkermansia muciniphila against Immune-Mediated Liver Injury
      in a Mouse Model.
AB  - Accumulating evidence indicates that gut microbiota participates in the
      pathogenesis and progression of liver diseases. The severity of immune-mediated
      liver injury is associated with different microbial communities. Akkermansia
      muciniphila can regulate immunologic and metabolic functions. However, little is
      known about its effects on gut microbiota structure and function. This study
      investigated the effect of A. muciniphila on immune-mediated liver injury and
      potential underlying mechanisms. Twenty-two C57BL/6 mice were assigned to three
      groups (N = 7-8 per group) and continuously administrated A. muciniphila MucT or
      PBS by oral gavage for 14 days. Mouse feces were collected for gut microbiota
      analysis on the 15th day, and acute liver injury was induced by Concanavalin A
      (Con A, 15 mg/kg) injection through the tail vein. Samples (blood, liver, ileum,
      colon) were assessed for liver injury, systemic inflammation, and intestinal
      barrier function. We found that oral administration of A. muciniphila decreased
      serum ALT and AST and alleviated liver histopathological damage induced by Con A.
      Serum levels of pro-inflammatory cytokines and chemokines (IL-2, IFN-gamma, IL
      12p40, MCP-1, MIP-1a, MIP-1b) were substantially attenuated. A. muciniphila
      significantly decreased hepatocellular apoptosis; Bcl-2 expression increased, but
      Fas and DR5 decreased. Further investigation showed that A. muciniphila enhanced
      expression of Occludin and Tjp-1 and inhibited CB1 receptor, which strengthened
      intestinal barriers and reduced systemic LPS level. Fecal 16S rRNA sequence
      analysis indicated that A. muciniphila increased microbial richness and
      diversity. The community structure of the Akk group clustered distinctly from
      that of mice pretreated with PBS. Relative abundance of Firmicutes increased, and
      Bacteroidetes abundance decreased. Correlation analysis showed that injury
      related factors (IL-12p40, IFN-gamma, DR5) were negatively associated with
      specific genera (Ruminococcaceae_UCG_009, Lachnospiraceae_UCG_001, Akkermansia),
      which were enriched in mice pretreated with A. muciniphila. Our results suggested
      that A. muciniphila MucT had beneficial effects on immune-mediated liver injury
      by alleviating inflammation and hepatocellular death. These effects may be driven
      by the protective profile of the intestinal community induced by the bacteria.
      The results provide a new perspective on the immune function of gut microbiota in
      host diseases.

PMID- 29033904
TI  - An Improved In-house MALDI-TOF MS Protocol for Direct Cost-Effective
      Identification of Pathogens from Blood Cultures.
AB  - Background: Bloodstream infection is a major cause of morbidity and mortality in
      hospitalized patients worldwide. Delays in the identification of microorganisms
      often leads to a poor prognosis. The application of matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) directly to
      blood culture (BC) broth can potentially identify bloodstream infections earlier,
      and facilitate timely management. Methods: We developed an "in-house" (IH)
      protocol for direct MALDI-TOF MS based identification of organisms in positive
      BCs. The IH protocol was initially evaluated and improved with spiked BC samples,
      and its performance was compared with the commercial SepsityperTM kit using both
      traditional and modified cut-off values. We then studied in parallel the
      performance of the IH protocol and the colony MS identifications in positive
      clinical BC samples using only modified cut-off values. All discrepancies were
      investigated by "gold standard" of gene sequencing. Results: In 54 spiked BC
      samples, the IH method showed comparable results with SepsityperTM after applying
      modified cut-off values. Specifically, accurate species and genus level
      identification was achieved in 88.7 and 3.9% of all the clinical monomicrobial
      BCs (284/301, 94.4%), respectively. The IH protocol exhibited superior
      performance for Gram negative bacteria than for Gram positive bacteria (92.8 vs.
      82.4%). For anaerobes and yeasts, accurate species identification was achieved in
      80.0 and 90.0% of the cases, respectively. For polymicrobial cultures (17/301,
      5.6%), MALDI-TOF MS correctly identified a single species present in all the
      polymicrobial BCs under the Standard mode, while using the MIXED method, two
      species were correctly identified in 52.9% of the samples. Comparisons based on
      BC bottle type, showed that the BACTECTM Lytic/10 Anaerobic/F culture vials
      performed the best. Conclusion: Our study provides a novel and effective sample
      preparation method for MALDI-TOF MS direct identification of pathogens from
      positive BC vials, with a lower cost ($1.5 vs. $ 7) albeit a slightly more
      laborious extracting process (an extra 15 min) compared with SepsityperTM kit.

PMID- 29033905
TI  - A Review on the Applications of Next Generation Sequencing Technologies as
      Applied to Food-Related Microbiome Studies.
AB  - The development of next generation sequencing (NGS) techniques has enabled
      researchers to study and understand the world of microorganisms from broader and
      deeper perspectives. The contemporary advances in DNA sequencing technologies
      have not only enabled finer characterization of bacterial genomes but also
      provided deeper taxonomic identification of complex microbiomes which in its
      genomic essence is the combined genetic material of the microorganisms inhabiting
      an environment, whether the environment be a particular body econiche (e.g.,
      human intestinal contents) or a food manufacturing facility econiche (e.g., floor
      drain). To date, 16S rDNA sequencing, metagenomics and metatranscriptomics are
      the three basic sequencing strategies used in the taxonomic identification and
      characterization of food-related microbiomes. These sequencing strategies have
      used different NGS platforms for DNA and RNA sequence identification.
      Traditionally, 16S rDNA sequencing has played a key role in understanding the
      taxonomic composition of a food-related microbiome. Recently, metagenomic
      approaches have resulted in improved understanding of a microbiome by providing a
      species-level/strain-level characterization. Further, metatranscriptomic
      approaches have contributed to the functional characterization of the complex
      interactions between different microbial communities within a single microbiome.
      Many studies have highlighted the use of NGS techniques in investigating the
      microbiome of fermented foods. However, the utilization of NGS techniques in
      studying the microbiome of non-fermented foods are limited. This review provides
      a brief overview of the advances in DNA sequencing chemistries as the technology
      progressed from first, next and third generations and highlights how NGS provided
      a deeper understanding of food-related microbiomes with special focus on non
      fermented foods.

PMID- 29033907
TI  - High-Salt Diet Has a Certain Impact on Protein Digestion and Gut Microbiota: A
      Sequencing and Proteome Combined Study.
AB  - High-salt diet has been considered to cause health problems, but it is still less
      known how high-salt diet affects gut microbiota, protein digestion, and passage
      in the digestive tract. In this study, C57BL/6J mice were fed low- or high-salt
      diets (0.25 vs. 3.15% NaCl) for 8 weeks, and then gut contents and feces were
      collected. Fecal microbiota was identified by sequencing the V4 region of 16S
      ribosomal RNA gene. Proteins and digested products of duodenal, jejunal, cecal,
      and colonic contents were identified by LC-MS-MS. The results indicated that the
      high-salt diet increased Firmicutes/Bacteroidetes ratio, the abundances of genera
      Lachnospiraceae and Ruminococcus (P < 0.05), but decreased the abundance of
      Lactobacillus (P < 0.05). LC-MS-MS revealed a dynamic change of proteins from the
      diet, host, and gut microbiota alongside the digestive tract. For dietary
      proteins, high-salt diet seemed not influence its protein digestion and
      absorption. For host proteins, 20 proteins of lower abundance were identified in
      the high-salt diet group in duodenal contents, which were involved in digestive
      enzymes and pancreatic secretion. However, no significant differentially
      expressed proteins were detected in jejunal, cecal, and colonic contents. For
      bacterial proteins, proteins secreted by gut microbiota were involved in energy
      metabolism, sodium transport, and protein folding. Five proteins (cytidylate
      kinase, trigger factor, 6-phosphogluconate dehydrogenase, transporter, and
      undecaprenyl-diphosphatase) had a higher abundance in the high-salt diet group
      than those in the low-salt group, while two proteins (acetylglutamate kinase and
      PBSX phage manganese-containing catalase) were over-expressed in the low-salt
      diet group than in the high-salt group. Consequently, high-salt diet may alter
      the composition of gut microbiota and has a certain impact on protein digestion.

PMID- 29033908
TI  - The Bacterial Species Campylobacter jejuni Induce Diverse Innate Immune Responses
      in Human and Avian Intestinal Epithelial Cells.
AB  - Campylobacter remain the major cause of human gastroenteritis in the Developed
      World causing a significant burden to health services. Campylobacter are
      pathogens in humans and chickens, although differences in mechanistic
      understanding are incomplete, in part because phenotypic strain diversity creates
      inconsistent findings. Here, we took Campylobacter jejuni isolates (n = 100) from
      multi-locus sequence typed collections to assess their pathogenic diversity,
      through their inflammatory, cytotoxicity, adhesion, invasion and signaling
      responses in a high-throughput model using avian and human intestinal epithelial
      cells. C. jejuni induced IL-8 and CXCLi1/2 in human and avian epithelial cells,
      respectively, in a MAP kinase-dependent manner. In contrast, IL-10 responses in
      both cell types were PI 3-kinase/Akt-dependent. C. jejuni strains showed diverse
      levels of invasion with high invasion dependent on MAP kinase signaling in both
      cell lines. C. jejuni induced diverse cytotoxic responses in both cell lines with
      cdt-positive isolates showing significantly higher toxicity. Blockade of
      endocytic pathways suggested that invasion by C. jejuni was clathrin- and dynamin
      dependent but caveolae- independent in both cells. In contrast, IL-8 (and
      CXCLi1/2) production was dependent on clathrin, dynamin, and caveolae. This study
      is important because of its scale, and the data produced, suggesting that avian
      and human epithelial cells use similar innate immune pathways where the magnitude
      of the response is determined by the phenotypic diversity of the Campylobacter
      species.

PMID- 29033909
TI  - Benzene and Naphthalene Degrading Bacterial Communities in an Oil Sands Tailings
      Pond.
AB  - Oil sands process-affected water (OSPW), produced by surface-mining of oil sands
      in Canada, is alkaline and contains high concentrations of salts, metals,
      naphthenic acids, and polycyclic aromatic compounds (PAHs). Residual hydrocarbon
      biodegradation occurs naturally, but little is known about the hydrocarbon
      degrading microbial communities present in OSPW. In this study, aerobic oxidation
      of benzene and naphthalene in the surface layer of an oil sands tailings pond
      were measured. The potential oxidation rates were 4.3 MUmol L-1 OSPW d-1 for
      benzene and 21.4 MUmol L-1 OSPW d-1 for naphthalene. To identify benzene and
      naphthalene-degrading microbial communities, metagenomics was combined with
      stable isotope probing (SIP), high-throughput sequencing of 16S rRNA gene
      amplicons, and isolation of microbial strains. SIP using 13C-benzene and 13C
      naphthalene detected strains of the genera Methyloversatilis and Zavarzinia as
      the main benzene degraders, while strains belonging to the family Chromatiaceae
      and the genus Thauera were the main naphthalene degraders. Metagenomic analysis
      revealed a diversity of genes encoding oxygenases active against aromatic
      compounds. Although these genes apparently belonged to many phylogenetically
      diverse taxa, only a few of these taxa were predominant in the SIP experiments.
      This suggested that many members of the community are adapted to consuming other
      aromatic compounds, or are active only under specific conditions. 16S rRNA gene
      sequence datasets have been submitted to the Sequence Read Archive (SRA) under
      accession number SRP109130. The Gold Study and Project submission ID number in
      Joint Genome Institute IMG/M for the metagenome is Gs0047444 and Gp0055765.

PMID- 29033906
TI  - Long Non-coding RNAs in Hepatitis C Virus-Infected Cells.
AB  - Hepatitis C virus (HCV) often leads to a chronic infection in the liver that may
      progress to steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC).
      Several viral and cellular factors are required for a productive infection and
      for the development of liver disease. Some of these are long non-coding RNAs
      (lncRNAs) deregulated in infected cells. After HCV infection, the sequence and
      the structure of the viral RNA genome are sensed to activate interferon (IFN)
      synthesis and signaling pathways. These antiviral pathways regulate transcription
      of several cellular lncRNAs. Some of these are also deregulated in response to
      viral replication. Certain viral proteins and/or viral replication can activate
      transcription factors such as MYC, SP1, NRF2, or HIF1alpha that modulate the
      expression of additional cellular lncRNAs. Interestingly, several lncRNAs
      deregulated in HCV-infected cells described so far play proviral or antiviral
      functions by acting as positive or negative regulators of the IFN system, while
      others help in the development of liver cirrhosis and HCC. The study of the
      structure and mechanism of action of these lncRNAs may aid in the development of
      novel strategies to treat infectious and immune pathologies and liver diseases
      such as cirrhosis and HCC.

PMID- 29033910
TI  - Resistance of Animal Strains of Pseudomonas aeruginosa to Carbapenems.
AB  - Carbapenems are major antibiotics reserved to human medicine. This study aimed to
      investigate the mechanisms of carbapenem resistance of a selection of Pseudomonas
      aeruginosa veterinary strains from the French network Resapath. Thirty (5.7%)
      imipenem and/or meropenem non-susceptible P. aeruginosa of canine (n = 24),
      feline (n = 5), or bovine (n = 1) origin were identified in a large collection of
      527 veterinary strains gathered by the Resapath. These resistant isolates
      belonged to 25 MultiLocus Sequence Types (MLST), of which 17 (68%) are shared
      with clinical (human) strains, such as high risk clones ST233 and ST395.
      Interestingly, none of the veterinary strains produced a carbapenemase, and only
      six of them (20%) harbored deletions or insertion sequence (IS) disrupting the
      porin OprD gene. The remaining 24 strains contained mutations or IS in various
      loci resulting in down-regulation of gene oprD coupled with upregulation of
      efflux system CzcCBA (n = 3; activation of sensor kinase CzcS +/- CopS), MexEF
      OprN (n = 4; alteration of oxido reductase MexS), MexXY (n = 8; activation of two
      component system ParRS), or MexAB-OprM (n = 12; alteration of regulator MexR,
      NalC +/- NalD). Two efflux pumps were co-produced simultaneously in three
      mutants. Finally, in 11 out of 12 strains displaying an intact porin OprD,
      derepression of MexAB-OprM accounted for a decreased susceptibility to meropenem
      relative to imipenem. Though not treated by carbapenems, animals thus represent a
      reservoir of multidrug resistant P. aeruginosa strains potentially able to
      contaminate fragile outpatients.

PMID- 29033914
TI  - Editorial: The Impact of Microorganisms on Consumption of Atmospheric Trace
      Gases.

PMID- 29033911
TI  - Characterization and Exploitation of CRISPR Loci in Bifidobacterium longum.
AB  - Diverse CRISPR-Cas systems provide adaptive immunity in many bacteria and most
      archaea, via a DNA-encoded, RNA-mediated, nucleic-acid targeting mechanism. Over
      time, CRISPR loci expand via iterative uptake of invasive DNA sequences into the
      CRISPR array during the adaptation process. These genetic vaccination cards thus
      provide insights into the exposure of strains to phages and plasmids in space and
      time, revealing the historical predatory exposure of a strain. These genetic loci
      thus constitute a unique basis for genotyping of strains, with potential of
      resolution at the strain-level. Here, we investigate the occurrence and diversity
      of CRISPR-Cas systems in the genomes of various Bifidobacterium longum strains
      across three sub-species. Specifically, we analyzed the genomic content of 66
      genomes belonging to B. longum subsp. longum, B. longum subsp. infantis and B.
      longum subsp. suis, and identified 25 strains that carry 29 total CRISPR-Cas
      systems. We identify various Type I and Type II CRISPR-Cas systems that are
      widespread in this species, notably I-C, I-E, and II-C. Noteworthy, Type I-C
      systems showed extended CRISPR arrays, with extensive spacer diversity. We show
      how these hypervariable loci can be used to gain insights into strain origin,
      evolution and phylogeny, and can provide discriminatory sequences to distinguish
      even clonal isolates. By investigating CRISPR spacer sequences, we reveal their
      origin and implicate phages and prophages as drivers of CRISPR immunity expansion
      in this species, with redundant targeting of select prophages. Analysis of CRISPR
      spacer origin also revealed novel PAM sequences. Our results suggest that CRISPR
      Cas immune systems are instrumental in mounting diversified viral resistance in
      B. longum, and show that these sequences are useful for typing across three
      subspecies.

PMID- 29033912
TI  - The Infectious Basis of ACPA-Positive Rheumatoid Arthritis.
AB  - Rheumatoid arthritis (RA) is associated with HLA-DRB1 shared epitope (HLA-DRB1SE)
      and anti-citrullinated protein autoantibodies (ACPAs). ACPAs precedes the onset
      of clinical and subclinical RA. There are strong data for three infectious agents
      as autoimmunity triggers in RA, namely Porphyromonas gingivalis and
      Aggregatibacter actinomycetemcomitans causes of periodontal disease (PD), and
      Epstein-Barr virus (EBV). P. gingivalis expresses arginine gingipains, that
      cleave proteins at the arginine residues, and peptidyl arginine deiminase (PPAD),
      which citrullinates arginine residues of proteins, thus forming neoantigens that
      lead to ACPA production. Peripheral blood plasmablasts from ACPA+RA patients
      produce ACPAs the majority of which react against P. gingivalis. A.
      actinocycetemcomitans produces leukotoxin A, a toxin that forms pores in the
      neutrophil membranes and leads to citrullination and release of citrullinated
      autoantigens in the gums. EBV can infect B cells and epithelial cells and resides
      as latent infection in resting B cells. Abs against citrullinated peptides
      derived from EBV nuclear antigen appear years before RA and cross-react with
      human citrullinated fibrin. Citrullinated proteins are potential arthritogenic
      autoantigens in RA. The conversion of arginine to citrulline increases the
      peptide binding affinity to HLA-DRB1SE. Also, citrullinated fibrinogen induces
      arthritis in HLA-DRB1*0401 transgenic mice, and transfer of their splenic T cells
      causes arthritis to recipient mice.

PMID- 29033913
TI  - Biochemical Function, Molecular Structure and Evolution of an Atypical
      Thioredoxin Reductase from Desulfovibrio vulgaris.
AB  - Thioredoxin reductase (TR) regulates the intracellular redox environment by
      reducing thioredoxin (Trx). In anaerobes, recent findings indicate that the Trx
      redox network is implicated in the global redox regulation of metabolism but also
      actively participates in protecting cells against O2. In the anaerobe
      Desulfovibrio vulgaris Hildenborough (DvH), there is an intriguing redundancy of
      the Trx system which includes a classical system using NADPH as electron source,
      a non-canonical system using NADH and an isolated TR (DvTRi). The functionality
      of DvTRi was questioned due to its lack of reactivity with DvTrxs. Structural
      analysis shows that DvTRi is a NAD(P)H-independent TR but its reducer needs still
      to be identified. Moreover, DvTRi reduced by an artificial electron source is
      able to reduce in turn DvTrx1 and complexation experiments demonstrate a direct
      interaction between DvTRi and DvTrx1. The deletion mutant tri exhibits a higher
      sensitivity to disulfide stress and the gene tri is upregulated by O2 exposure.
      Having DvTRi in addition to DvTR1 as electron source for reducing DvTrx1 must be
      an asset to combat oxidative stress. Large-scale phylogenomics analyses show that
      TRi homologs are confined within the anaerobes. All TRi proteins displayed a
      conserved TQ/NGK motif instead of the HRRD motif, which is selective for the
      binding of the 2'-phosphate group of NADPH. The evolutionary history of TRs
      indicates that tr1 is the common gene ancestor in prokaryotes, affected by both
      gene duplications and horizontal gene events, therefore leading to the appearance
      of TRi through subfunctionalization over the evolutionary time.

PMID- 29033915
TI  - Evaluation of the Swabbing of Disposable Absorbent Incontinence Products for
      Assessing the Carriage of Multiresistant Enterobacteriaceae in Nursing Home
      Residents.
AB  - We compared the performance of incontinence product (IP) and rectal swabbing for
      the detection of multidrug-resistant Enterobacteriaceae (MDRE) carriage in a
      large multicenter study conducted in February 2017 among the residents of 23
      French nursing homes. The study included 547 residents who habitually wore IP, 88
      of whom were MDRE carriers (16.1%). Positive results were obtained for both
      rectal and IP swabs for 64 of these residents, for rectal swabs only for 22 and
      for IP swabs only for two of these patients. The estimated prevalence of MDRE
      carriage depended on the type of sample: 15.7% for rectal swabs and 12.1% for IP
      swabs (p < 0.001). The positive percent agreement was 84.2% and the negative
      percent agreement was 97.4%. Rectal swabbing remains the best method for
      detecting MDRE carriage in elderly residents, but our findings provide support
      for the use of swabs from IP used overnight to increase response rates in MDRE
      surveys in elderly residents that habitually wear IP, when rectal swabbing is not
      feasible.

PMID- 29033916
TI  - Contribution of Ruminal Fungi, Archaea, Protozoa, and Bacteria to the Methane
      Suppression Caused by Oilseed Supplemented Diets.
AB  - Dietary lipids can suppress methane emission from ruminants, but effects are
      variable. Especially the role of bacteria, archaea, fungi and protozoa in
      mediating the lipid effects is unclear. In the present in vitro study, archaea,
      fungi and protozoa were selectively inhibited by specific agents. This was fully
      or almost fully successful for fungi and protozoa as well as archaeal activity as
      determined by the methyl-coenzyme M reductase alpha subunit gene. Five different
      microbial treatments were generated: rumen fluid being intact (I), without
      archaea (-A), without fungi (-F), without protozoa (-P) and with bacteria only (
      AFP). A forage-concentrate diet given alone or supplemented with crushed full-fat
      oilseeds of either safflower (Carthamus tinctorius) or poppy (Papaver somniferum)
      or camelina (Camelina sativa) at 70 g oil kg-1 diet dry matter was incubated.
      This added up to 20 treatments with six incubation runs per treatment. All
      oilseeds suppressed methane emission compared to the non-supplemented control.
      Compared to the non-supplemented control, -F decreased organic matter (OM)
      degradation, and short-chain fatty acid concentration was greater with camelina
      and safflower seeds. Methane suppression per OM digested in -F was greater with
      camelina seeds (-12 vs.-7% with I, P = 0.06), but smaller with poppy seeds (-4
      vs. -8% with I, P = 0.03), and not affected with safflower seeds. With -P,
      camelina seeds decreased the acetate-to-propionate ratio and enhanced the methane
      suppression per gram dry matter (18 vs. 10% with I, P = 0.08). Hydrogen recovery
      was improved with -P in any oilseeds compared to non-supplemented control. No
      methane emission was detected with the -A and -AFP treatments. In conclusion,
      concerning methanogenesis, camelina seeds seem to exert effects only on archaea
      and bacteria. By contrast, with safflower and poppy seeds methane was obviously
      reduced mainly through the interaction with protozoa or archaea associated with
      protozoa. This demonstrated that the microbial groups differ in their
      contribution to the methane suppressing effect dependent on the source of lipid.
      These findings help to understand how lipid supplementation and microbial groups
      interact, and thus may assist in making this methane mitigation tool more
      efficient, but await confirmation in vivo.

PMID- 29033917
TI  - Newly Isolated Bacteriophages from the Podoviridae, Siphoviridae, and Myoviridae
      Families Have Variable Effects on Putative Novel Dickeya spp.
AB  - Soft rot pathogenic bacteria from the genus Dickeya cause severe economic losses
      in orchid nurseries worldwide, and there is no effective control currently
      available. In the last decade, the genus Dickeya has undergone multiple changes
      as multiple new taxa have been described, and just recently a new putative
      Dickeya species was reported. This study reports the isolation of three
      bacteriophages active against putative novel Dickeya spp. isolates from
      commercially produced infected orchids that show variable host-range profiles.
      Bacteriophages were isolated through enrichment from Dickeya-infected orchid
      tissue. Convective interaction media monolith chromatography was used to isolate
      bacteriophages from wastewaters, demonstrating its suitability for the isolation
      of infective bacteriophages from natural sources. Based on bacteriophage
      morphology, all isolated bacteriophages were classified as being in the order
      Caudovirales, belonging to three different families, Podoviridae, Myoviridae, and
      Siphoviridae. The presence of three different groups of bacteriophages was
      confirmed by analyzing the bacteriophage specificity of bacterial hosts,
      restriction fragment length polymorphism and plaque morphology. Bacteriophage
      BF25/12, the first reported Podoviridae bacteriophage effective against Dickeya
      spp., was selected for further characterization. Its genome sequence determined
      by next-generation sequencing showed limited similarity to other characterized
      Podoviridae bacteriophages. Interactions among the bacteriophages and Dickeya
      spp. were examined using transmission electron microscopy, which revealed
      degradation of electron-dense granules in response to bacteriophage infection in
      some Dickeya strains. The temperature stability of the chosen Podoviridae
      bacteriophage monitored over 1 year showed a substantial decrease in the survival
      of bacteriophages stored at -20 degrees C over longer periods. It showed
      susceptibility to low pH and UV radiation but was stable in neutral and alkaline
      pH. Furthermore, the stability of the tested bacteriophage was also connected to
      the incubation medium and bacteriophage concentration at certain pH values.
      Finally, the emergence of bacteriophage-resistant bacterial colonies is highly
      connected to the concentration of bacteriophages in the bacterial environment.
      This is the first report on bacteriophages against Dickeya from the Podoviridae
      family to expand on potential bacteriophages to include in bacteriophage
      cocktails as biocontrol agents. Some of these bacteriophage isolates also showed
      activity against Dickeya solani, an aggressive strain that causes the soft rot of
      potatoes, which indicates their broad potential as biocontrol agents.

PMID- 29033918
TI  - DNA-Sequence Based Typing of the Cronobacter Genus Using MLST, CRISPR-cas Array
      and Capsular Profiling.
AB  - The Cronobacter genus is composed of seven species, within which a number of
      pathovars have been described. The most notable infections by Cronobacter spp.
      are of infants through the consumption of contaminated infant formula. The
      description of the genus has greatly improved in recent years through DNA
      sequencing techniques, and this has led to a robust means of identification.
      However some species are highly clonal and this limits the ability to
      discriminate between unrelated strains by some methods of genotyping. This
      article updates the application of three genotyping methods across the
      Cronobacter genus. The three genotyping methods were multilocus sequence typing
      (MLST), capsular profiling of the K-antigen and colanic acid (CA) biosynthesis
      regions, and CRISPR-cas array profiling. A total of 1654 MLST profiled and 286
      whole genome sequenced strains, available by open access at the PubMLST
      Cronobacter database, were used this analysis. The predominance of C. sakazakii
      and C. malonaticus in clinical infections was confirmed. The majority of clinical
      strains being in the C. sakazakii clonal complexes (CC) 1 and 4, sequence types
      (ST) 8 and 12 and C. malonaticus ST7. The capsular profile K2:CA2, previously
      proposed as being strongly associated with C. sakazakii and C. malonaticus
      isolates from severe neonatal infections, was also found in C. turicensis, C.
      dublinensis and C. universalis. The majority of CRISPR-cas types across the genus
      was the I-E (Ecoli) type. Some strains of C. dublinensis and C. muytjensii
      encoded the I-F (Ypseudo) type, and others lacked the cas gene loci. The
      significance of the expanding profiling will be of benefit to researchers as well
      as governmental and industrial risk assessors.

PMID- 29033919
TI  - Adaptation of Methanogenic Inocula to Anaerobic Digestion of Maize Silage.
AB  - A well-balanced microbial consortium is crucial for efficient biogas production.
      In turn, one of a major factor that influence on the structure of anaerobic
      digestion (AD) consortium is a source of microorganisms which are used as an
      inoculum. This study evaluated the influence of inoculum sources (with various
      origin) on adaptation of a biogas community and the efficiency of the
      biomethanization of maize silage. As initial inocula for AD of maize silage the
      samples from: (i) an agricultural biogas plant (ABP) which utilizes maize silage
      as a main substrate, (ii) cattle slurry (CS), which contain elevated levels of
      lignocelluloses materials, and (iii) raw sewage sludge (RSS) with low content of
      plant origin materials were used. The adaptation of methanogenic consortia was
      monitored during a series of passages, and the functionality of the adapted
      consortia was verified through start-up operation of AD in two-stage reactors.
      During the first stages of the adaptation phase, methanogenic consortia occurred
      very slowly, and only after several passages did the microbial community adapts
      to allow production of biogas with high methane content. The ABP consortium
      revealed highest biogas production in the adaptation and in the start-up process.
      The biodiversity dynamics monitored during adaptation and start-up process showed
      that community profile changed in a similar direction in three studied consortia.
      Native communities were very distinct to each other, while at the end of the
      Phase II of the start-up process microbial diversity profile was similar in all
      consortia. All adopted bacterial communities were dominated by representatives of
      Porphyromonadaceae, Rikenellaceae, Ruminococcaceae, and Synergistaceae. A shift
      from low acetate-preferring acetoclastic Methanosaetaceae (ABP and RSS) and/or
      hydrogenotrophic Archaea, e.g., Methanomicrobiaceae (CS) prevailing in the
      inoculum samples to larger populations of high acetate-preferring acetoclastic
      Methanosarcinaceae was observed by the end of the experiment. As a result, three
      independent, functional communities that syntrophically produced methane from
      acetate (primarily) and H2/CO2, methanol and methylamines were adapted. This
      study provides new insights into the specific process by which different inocula
      sampled from typical methanogenic environments that are commonly used to initiate
      industrial installations gradually adapted to allow biogas production from maize
      silage.

PMID- 29033922
TI  - Endophytic Bacteria Improve Plant Growth, Symbiotic Performance of Chickpea
      (Cicer arietinum L.) and Induce Suppression of Root Rot Caused by Fusarium solani
      under Salt Stress.
AB  - Salinity causes disturbance in symbiotic performance of plants, and increases
      susceptibility of plants to soil-borne pathogens. Endophytic bacteria are an
      essential determinant of cross-tolerance to biotic and abiotic stresses in
      plants. The aim of this study was to isolate non-rhizobial endophytic bacteria
      from the root nodules of chickpea (Cicer arietinum L.), and to assess their
      ability to improve plant growth and symbiotic performance, and to control root
      rot in chickpea under saline soil conditions. A total of 40 bacterial isolates
      from internal root tissues of chickpea grown in salinated soil were isolated.
      Four bacterial isolates, namely Bacillus cereus NUU1, Achromobacter xylosoxidans
      NUU2, Bacillus thuringiensis NUU3, and Bacillus subtilis NUU4 colonizing root
      tissue demonstrated plant beneficial traits and/or antagonistic activity against
      F. solani and thus were characterized in more detail. The strain B. subtilis NUU4
      proved significant plant growth promotion capabilities, improved symbiotic
      performance of host plant with rhizobia, and promoted yield under saline soil as
      compared to untreated control plants under field conditions. A combined
      inoculation of chickpea with M. ciceri IC53 and B. subtilis NUU4 decreased H2O2
      concentrations and increased proline contents compared to the un-inoculated
      plants indicating an alleviation of adverse effects of salt stress. Furthermore,
      the bacterial isolate was capable to reduce the infection rate of root rot in
      chickpea caused by F. solani. This is the first report of F. solani causing root
      rot of chickpea in a salinated soil of Uzbekistan. Our findings demonstrated that
      the endophytic B. subtilis strain NUU4 provides high potentials as a stimulator
      for plant growth and as biological control agent of chickpea root rot under
      saline soil conditions. These multiple relationships could provide promising
      practical approaches to increase the productivity of legumes under salt stress.

PMID- 29033921
TI  - Influence of Oral and Gut Microbiota in the Health of Menopausal Women.
AB  - Sex differences in gut microbiota are acknowledged, and evidence suggests that
      gut microbiota may have a role in higher incidence and/or severity of autoimmune
      diseases in females. Additionally, it has been suggested that oral, vaginal, and
      gut microbiota composition can be regulated by estrogen levels. The association
      of vaginal microbiota with vulvovaginal atrophy at menopause is well described in
      the literature. However, the relevance of oral and gut microbiota modulation in
      the immune system during estrogen deficiency and its effect on inflammatory
      diseases is not well explored. Estrogen deficiency is a condition that occurs in
      menopausal women, and it can last approximately 30 years of a woman's life. The
      purpose of this mini- review is to highlight the importance of alterations in the
      oral and gut microbiota during estrogen deficiency and their effect on oral and
      inflammatory diseases that are associated with menopause. Considering that
      hormone replacement therapy is not always recommended or sufficient to prevent or
      treat menopause-related disease, we will also discuss the use of probiotics and
      prebiotics as an option for the prevention or treatment of these diseases.

PMID- 29033920
TI  - DNA Repair and Photoprotection: Mechanisms of Overcoming Environmental
      Ultraviolet Radiation Exposure in Halophilic Archaea.
AB  - Halophilic archaea push the limits of life at several extremes. In particular,
      they are noted for their biochemical strategies in dealing with osmotic stress,
      low water activity and cycles of desiccation in their hypersaline environments.
      Another feature common to their habitats is intense ultraviolet (UV) radiation,
      which is a challenge that microorganisms must overcome. The consequences of high
      UV exposure include DNA lesions arising directly from bond rearrangement of
      adjacent bipyrimidines, or indirectly from oxidative damage, which may ultimately
      result in mutation and cell death. As such, these microorganisms have evolved a
      number of strategies to navigate the threat of DNA damage, which we differentiate
      into two categories: DNA repair and photoprotection. Photoprotection encompasses
      damage avoidance strategies that serve as a "first line of defense," and in
      halophilic archaea include pigmentation by carotenoids, mechanisms of oxidative
      damage avoidance, polyploidy, and genomic signatures that make DNA less
      susceptible to photodamage. Photolesions that do arise are addressed by a number
      of DNA repair mechanisms that halophilic archaea efficiently utilize, which
      include photoreactivation, nucleotide excision repair, base excision repair, and
      homologous recombination. This review seeks to place DNA damage, repair, and
      photoprotection in the context of halophilic archaea and the solar radiation of
      their hypersaline environments. We also provide new insight into the breadth of
      strategies and how they may work together to produce remarkable UV-resistance for
      these microorganisms.

PMID- 29033924
TI  - Rethinking Tertiary Models: Relationships between Growth Parameters of Bacillus
      cereus Strains.
AB  - The maximum specific growth rates of 12 strains, pair-wise belonging to six
      groups of Bacillus cereus sensu lato, were fitted against temperature by a
      reparametrized version of the model of Ratkowsky et al. (1983). This way, the
      interpretation of the new parameter set was similar to that of the cardinal
      values-model of Rosso and Robinson (2001), both models including the minimum,
      optimum and maximum temperatures for growth as well as a fourth parameter scaling
      along the dependent variable. The modularity of the reparametrized version of the
      Ratkowsky model was utilized to show a so-far undetected relationship between
      this scaling parameter and the cardinal temperatures, which linked even distant
      (e.g., mesophilic and psychotropic) strains of B. cereus. We propose that the
      name "tertiary modeling" should be used for investigations like ours, as
      logically derived from the concepts of "primary" and "secondary" modeling. Such
      tertiary models may reveal biological relationships between kinetic parameters
      within a group of strains. It can also be used to create an overarching
      predictive model for mixed cultures, when different strains grow together but
      independently of each other.

PMID- 29033923
TI  - Emerging Trends in "Smart Probiotics": Functional Consideration for the
      Development of Novel Health and Industrial Applications.
AB  - The link between gut microbiota and human health is well-recognized and
      described. This ultimate impact on the host has contributed to explain the mutual
      dependence between humans and their gut bacteria. Gut microbiota can be
      manipulated through passive or active strategies. The former includes diet,
      lifestyle, and environment, while the latter comprise antibiotics, pre- and
      probiotics. Historically, conventional probiotic strategies included a
      phylogenetically limited diversity of bacteria and some yeast strains. However,
      biotherapeutic strategies evolved in the last years with the advent of fecal
      microbiota transplant (FMT), successfully applied for treating CDI, IBD, and
      other diseases. Despite the positive outcomes, long-term effects resulting from
      the uncharacterized nature of FMT are not sufficiently studied. Thus, developing
      strategies to simulate the FMT, using characterized gut colonizers with
      identified phylogenetic diversity, may be a promising alternative. As the
      definition of probiotics states that the microorganism should have beneficial
      effects on the host, several bacterial species with proven efficacy have been
      considered next generation probiotics. Non-conventional candidate strains include
      Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides fragilis, and
      members of the Clostridia clusters IV, XIVa, and XVIII. However, viable
      intestinal delivery is one of the current challenges, due to their stringent
      survival conditions. In this review, we will cover current perspectives on the
      development and assessment of next generation probiotics and the approaches that
      industry and stakeholders must consider for a successful outcome.

PMID- 29033925
TI  - Caco-2 Invasion by Cronobacter sakazakii and Salmonella enterica Exposed to
      Drying and Heat Treatments in Dried State in Milk Powder.
AB  - Due to the ability of foodborne pathogens to survive in low moisture food, the
      decontamination of milk powder is an important issue in food protection. The
      safety of food products is, however, not always insured and the different steps
      in the processing of food involve physiological and metabolic changes in
      bacteria. Among these changes, virulence properties may also be affected. In this
      study, the effect of drying and successive thermal treatments on the invasion
      capacity of Salmonella Typhimurium, Salmonella Senftenberg, and Cronobacter
      sakazakii was assessed. Bacteria were dried on milk powder at three different
      water activity levels (0.25, 0.58, and 0.80) and heated at two different
      temperatures (90 degrees C and 100 degrees C) for 30 and 120 s. After recovery,
      stressed bacterial populations were placed in contact with Caco-2 cells to
      estimate their invasion capacity. Our results show that drying increases the
      invasion capacity of foodborne pathogens, but that heat treatment in the dried
      state did not exert a selective pressure on bacterial cells depending on their
      invasion capacity after drying. Taken together, our findings add to the sum of
      knowledge on food safety in dried food products and provide insight into the
      effects of food processing.

PMID- 29033927
TI  - Editorial: Mycoplasma pneumoniae Clinical Manifestations, Microbiology, and
      Immunology.

PMID- 29033926
TI  - MicroRNAs in Taenia solium Neurocysticercosis: Insights as Promising Agents in
      Host-Parasite Interaction and Their Potential as Biomarkers.
AB  - MicroRNAs (miRNAs) are short, endogenous, non-coding, single-stranded RNAs
      involved in post-transcriptional gene regulation. Although, several miRNAs have
      been identified in parasitic helminths, there is little information about their
      identification and function in Taenia. Furthermore, the impact of miRNAs in
      neurocysticercosis, the brain infection caused by larvae of Taenia solium is
      still unknown. During chronic infection, T. solium may activate numerous
      mechanisms aimed to modulate host immune responses. Helminthic miRNAs might also
      have effects on host mRNA expression and thus play an important role regulating
      host-parasite interactions. Also, the diagnosis of this disease is difficult and
      it usually requires neuroimaging and confirmatory serology. Since miRNAs are
      stable when released, they can be detected in body fluids and therefore have
      potential to diagnose infection, determine parasite burden, and ascertain
      effectiveness of treatment or disease progression, for instance. This review
      discusses the potential roles of miRNAs in T. solium infection, including
      regulation of host-parasite relationships and their eventual use as diagnostic or
      disease biomarkers. Additionally, we summarize the bioinformatics resources
      available for identification of T. solium miRNAs and prediction of their targets.

PMID- 29033928
TI  - Unexpectedly High Prevalence of Common Variable Immunodeficiency in Finland.
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is the most common primary
      immunodeficiency. Prevalence varies greatly between countries and studies. Most
      diagnostic criteria include hypogammaglobulinemia and impaired vaccine response.
      AIM: To evaluate the minimum prevalence as well as the clinical and immunological
      phenotypes of CVID in Southern Finland. METHODS: We performed a cross-sectional
      study to assess all adult CVID patients followed up in three hospital districts
      in Southern and South-Eastern Finland between April 2007 and August 2015. CVID
      diagnosis was based, with a minor modification, on the ESID/PAGID criteria for
      primary CVID. Antipolysaccharide responses to Pneumovax(r) were defined as
      impaired only if 50% or more of the serotypes did not reach a level of 0.35 ug/mL
      after vaccination. We further characterized the patients' B cell phenotypes and
      complications associated with CVID. RESULTS: In total, 9 patients were excluded
      due to potential secondary causes before diagnosis. ESID/PAGID criteria were met
      by 132 patients (males 52%), of whom, 106 had "probable" and 26 "possible CVID."
      Based on the population statistics in the three hospital districts, the minimum
      adult prevalence per 100,000 inhabitants in Finland for all CVID ("probable
      CVID," respectively) patients was 6.9 (5.5). In the highest prevalence district
      (Helsinki and Uusimaa), the prevalence was 7.7 (6.1). CVID patients suffer from
      frequent complications. Ten patients died during follow-up. Of probable CVID
      patients, 73% had more than one clinical phenotype. Intriguingly, gradual B cell
      loss from peripheral blood during follow-up was seen in as many as 16% of
      "probable CVID" patients. Patients with possible CVID displayed somewhat milder
      clinical and laboratory phenotypes than probable CVID patients. We also confirm
      that large granular lymphocyte lymphoproliferation is a CVID-associated
      complication. CONCLUSION: The prevalence of CVID in Finland appears the highest
      recorded, likely reflecting the genetic isolation and potential founder effects
      in the Finnish population. Studies to discover potential gene variants
      responsible for the high prevalence in Finland thus seem warranted. Increased
      awareness of CVID among physicians would likely lead to earlier diagnosis and
      improved quality of care.

PMID- 29033932
TI  - From Cocoa to Chocolate: The Impact of Processing on In Vitro Antioxidant
      Activity and the Effects of Chocolate on Antioxidant Markers In Vivo.
AB  - Chocolate is a product processed from cocoa rich in flavonoids, antioxidant
      compounds, and bioactive ingredients that have been associated with both its
      healthy and sensory properties. Chocolate production consists of a multistep
      process which, starting from cocoa beans, involves fermentation, drying,
      roasting, nib grinding and refining, conching, and tempering. During cocoa
      processing, the naturally occurring antioxidants (flavonoids) are lost, while
      others, such as Maillard reaction products, are formed. The final content of
      antioxidant compounds and the antioxidant activity of chocolate is a function of
      several variables, some related to the raw material and others related to
      processing and formulation. The aim of this mini-review is to revise the
      literature on the impact of full processing on the in vitro antioxidant activity
      of chocolate, providing a critical analysis of the implications of processing on
      the evaluation of the antioxidant effect of chocolate in in vivo studies in
      humans.

PMID- 29033933
TI  - Monocyte Chemotactic Protein 1 in Plasma from Soluble Leishmania Antigen
      Stimulated Whole Blood as a Potential Biomarker of the Cellular Immune Response
      to Leishmania infantum.
AB  - New biomarkers are needed to identify asymptomatic Leishmania infection as well
      as immunity following vaccination or treatment. With the aim of finding a robust
      biomarker to assess an effective cellular immune response, monocyte chemotactic
      protein 1 (MCP-1) was examined in plasma from soluble Leishmania antigen (SLA)
      stimulated whole blood collected from subjects living in a Leishmania infantum
      endemic area. MCP-1, expressed 110 times more strongly than IL-2, identified
      87.5% of asymptomatic subjects and verified some asymptomatic subjects close to
      the cutoff. MCP-1 was also significantly elevated in all patients cured of
      visceral leishmaniasis (VL), unlike IL-2, indicating the specific memory response
      generated against Leishmania. These results show MCP-1 to be a robust candidate
      biomarker of immunity that could be used as a marker of cure and to both select
      and follow the population in vaccine phase I-III human clinical trials with
      developed rapid, easy-to-use field tools.

PMID- 29033930
TI  - Immunomodulatory Effects of Calcium and Strontium Co-Doped Titanium Oxides on
      Osteogenesis.
AB  - The effects of calcium (Ca) or strontium (Sr) on host osteogenesis and immune
      responses have been investigated separately. In clinical practice, these two
      elements may both be present around an orthopedic device, but their potential
      synergistic effects on osteogenesis and the immune response have not been
      explored to date. In this work, we investigated the immunomodulatory effects of
      Ca and Sr co-doped titanium oxides on osteogenesis in vitro using the mouse
      macrophage cell line RAW 264.7 alone and in co-culture with mouse bone
      mesenchymal stem cells (BMSCs), and in vivo using a mouse air-pouch model.
      Coatings containing Ca and Sr at different concentration ratios were fabricated
      on titanium substrates using micro-arc oxidation and electrochemical treatment.
      The in vitro and in vivo results demonstrated that the Ca and Sr concentration
      ratio has a marked influence on macrophage polarization. The coating with a Ca/Sr
      ratio of 2:1 was superior to those with other Ca and/or Sr concentrations in
      terms of modulating M2 polarization, which enhanced osteogenic differentiation of
      mouse BMSCs in co-culture. These findings suggest that the osteoimmunomodulatory
      effect of a titanium-oxide coating can be enhanced by modulating the
      concentration ratio of its components.

PMID- 29033929
TI  - Immunity and Fibrogenesis: The Role of Th17/IL-17 Axis in HBV and HCV-induced
      Chronic Hepatitis and Progression to Cirrhosis.
AB  - Cirrhosis is a common final pathway for most chronic liver diseases; representing
      an increasing burden worldwide and is associated with increased morbidity and
      mortality. Current evidence has shown that, after an initial injury, the immune
      response has a significant participation in the ongoing damage, and progression
      from chronic viral hepatitis (CVH) to cirrhosis, driving the activation and
      maintenance of main fibrogenic pathways. Among immune deregulations, those
      related to the subtype 17 of T helper lymphocytes (Th17)/interleukin-17 (IL-17)
      axis have been recognized as key immunopathological and prognostic elements in
      patients with CVH. The Th17/IL-17 axis has been found involved in several points
      of fibrogenesis chain from the activation of stellate cells, increased expression
      of profibrotic factors as TGF-beta, promotion of the myofibroblastic or
      epithelial-mesenchymal transition, stimulation of the synthesis of collagen, and
      induction of imbalance between matrix metalloproteinases and tissue inhibitors of
      metalloproteinases (TIMPs). It also promotes the recruitment of inflammatory
      cells and increases the expression of proinflammatory cytokines such as IL-6 and
      IL-23. So, the Th17/IL-17 axis is simultaneously the fuel and the flame of a
      sustained proinflammatory and profibrotic environment. This work aims to present
      the immunopathologic and prognostic role of the Th17/IL-17 axis and related
      pathways in fibrogenesis and progression to cirrhosis in patients with liver
      disease due to hepatitis B virus (HBV) and hepatitis C virus (HCV).

PMID- 29033931
TI  - Plasmodium berghei NK65 in Combination with IFN-gamma Induces Endothelial
      Glucocorticoid Resistance via Sustained Activation of p38 and JNK.
AB  - Malaria-associated acute respiratory distress syndrome (MA-ARDS) is an often
      lethal complication of malaria. Currently, no adequate therapy for this syndrome
      exists. Although glucocorticoids (GCs) have been used to improve clinical outcome
      of ARDS, their therapeutic benefits remain unclear. We previously developed a
      mouse model of MA-ARDS, in which dexamethasone treatment revealed GC resistance.
      In the present study, we investigated GC sensitivity of mouse microvascular lung
      endothelial cells stimulated with interferon-gamma (IFN-gamma) and Plasmodium
      berghei NK65 (PbNK65). Upon challenge with IFN-gamma alone, dexamethasone
      inhibited the expression of CCL5 (RANTES) by 90% and both CCL2 (MCP-1) and CXCL10
      (IP-10) by 50%. Accordingly, whole transcriptome analysis revealed that
      dexamethasone differentially affected several gene clusters and in particular
      inhibited a large cluster of IFN-gamma-induced genes, including chemokines. In
      contrast, combined stimulation with IFN-gamma and PbNK65 extract impaired
      inhibitory actions of GCs on chemokine release, without affecting the capacity of
      the GC receptor to accumulate in the nucleus. Subsequently, we investigated the
      effects of GCs on two signaling pathways activated by IFN-gamma. Dexamethasone
      left phosphorylation and protein levels of signal transducer and activator of
      transcription 1 (STAT1) unhampered. In contrast, dexamethasone inhibited the IFN
      gamma-induced activation of two mitogen-activated protein kinases (MAPK), JNK,
      and p38. However, PbNK65 extract abolished the inhibitory effects of GCs on MAPK
      signaling, inducing GC resistance. These data provide novel insights into the
      mechanisms of GC actions in endothelial cells and show how malaria may impair the
      beneficial effects of GCs.

PMID- 29033934
TI  - Ebi3 Prevents Trypanosoma cruzi-Induced Myocarditis by Dampening IFN-gamma-Driven
      Inflammation.
AB  - The identification of anti-inflammatory mediators can reveal important targetable
      molecules capable of counterbalancing Trypanosoma cruzi-induced myocarditis.
      Composed of Ebi3 and IL-27p28 subunits, IL-27 is produced by myeloid cells and is
      able to suppress inflammation by inducing IL-10-producing Tr1 cells, thus
      emerging as a potential candidate to ameliorate cardiac inflammation induced by
      T. cruzi. Although IL-27 has been extensively characterized as a suppressive
      cytokine that prevents liver immunopathogenesis after T. cruzi infection, the
      mechanisms underlying its effects on T. cruzi-induced myocarditis remain largely
      unknown. Here, wild-type (WT) and Ebi3-deficient animals were intraperitoneally
      infected with trypomastigotes of T. cruzi Y strain and used to evaluate the
      potential anti-inflammatory properties of Ebi3 during T. cruzi infection. The
      survival rates of mice were daily recorded, the frequency of inflammatory cells
      was analyzed by flow cytometry and inflammatory mediators were measured by ELISA,
      real-time PCR and PCR array. We reported that T. cruzi-induced myocarditis was
      prevented by Ebi3. Stressors mainly recognized by TLR2 and TLR4 receptors on
      myeloid cells were essential to trigger IL-27p28 production. In addition, Ebi3
      regulated IFN-gamma-mediated myocarditis by promoting an anti-inflammatory
      environment through IL-10, which was most likely produced by Tr1 cells rather
      than classical regulatory T cells (Tregs), in the heart tissue of T. cruzi
      infected animals. Furthermore, in vivo IFN-gamma blockade ameliorated the host
      survival without compromising the parasite control in the bloodstream. In humans,
      IL-27p28 was correlated with cardiac protection during Chagas disease. Patients
      with mild clinical forms of the disease produced high levels of IL-27p28, whereas
      lower levels were found in those with severe forms. In addition, polymorphic
      sites at Ebi3 gene were associated with severe cardiomyopathy in patients with
      Chagas disease. Collectively, we describe a novel regulatory mechanism where Ebi3
      dampens cardiac inflammation by modulating the overproduction of IFN-gamma, the
      bona fide culprit of Chagas disease cardiomyopathy.

PMID- 29033937
TI  - Commentary: CD6 As a Potential Target for Treating Multiple Sclerosis.

PMID- 29033935
TI  - Cannabinoid Receptor 1 Participates in Liver Inflammation by Promoting M1
      Macrophage Polarization via RhoA/NF-kappaB p65 and ERK1/2 Pathways, Respectively,
      in Mouse Liver Fibrogenesis.
AB  - : Macrophage M1/M2 polarization mediates tissue damage and inflammatory
      responses. Cannabinoid receptor (CB) 1 participated in liver fibrogenesis by
      affecting bone marrow (BM)-derived monocytes/macrophages (BMMs) activation.
      However, the knowledge of whether CB1 is involved in the polarization of BMMs
      remains limited. Here, we found M1 gene signatures (including CD86, MIP-1beta,
      tumor necrosis factor, IL-6, and inducible nitric oxide synthase) and the amount
      of M1 macrophages (CD86+ cells, gated by F4/80) were significantly elevated in
      carbon tetrachloride (CCl4)-induced mouse injured livers, while that of M2 type
      macrophages had little change by RT-qPCR and fluorescence-activated cell sorting
      (FACS). Our preceding study confirmed CB1 was involved in CCl4-induced liver
      fibrogenesis. Our results noted CB1 expression showed positive correlation with
      CD86. Blockade of CB1 by its antagonist or siRNA in vivo downregulated the mRNA
      and protein levels of M1 markers using RT-qPCR, western blot, and Cytometric Bead
      Array (CBA) assays, and reduced the proportion of M1 macrophages. Moreover,
      chimera mouse models, which received BM transplants from EGFP-transgenic mice or
      clodronate liposome injection mouse models, in which Kupffer cells were depleted,
      were performed to clarify the role of CB1 on the polarization of Kupffer cells
      and BMMs. We found that CB1 was especially involved in BMM polarization toward M1
      phenotype but have no effect on that of Kupffer cells. The reason might due to
      the lower CB1 expression in Kupffer cells than that of BMMs. In vitro, we
      discovered CB1 was involved in the polarization of BMMs toward M1. Furthermore,
      CB1-induced M1 polarization was apparently impaired by PTX [G(alpha)i/o protein
      inhibitor], Y27632 (ROCK inhibitor), and PD98059 [extracellular signal-regulated
      kinase (ERK) inhibitor], while SB203580 (p38 inhibitor) and compound C (AMPK
      inhibitor) had no such effect. ACEA (CB1 agonist) activated G(alpha)i/o coupled
      CB1, then enlarged GTP-bound Rho and phosphor-ERK1/2, independently. NF-kappaB
      p65 nuclear translocation is also a marker of M1 phenotype macrophages. We found
      that CB1 switched on NF-kappaB p65 nuclear translocation only depending on
      G(alpha)i/o/RhoA signaling pathway. CONCLUSION: CB1 plays a crucial role in
      regulating M1 polarization of BMMs in liver injury, depending on two independent
      signaling pathways: G(alpha)i/o/RhoA/NF-kappaB p65 and G(alpha)i/o/ERK1/2
      pathways.

PMID- 29033938
TI  - Early-Life Nutritional Factors and Mucosal Immunity in the Development of
      Autoimmune Diabetes.
AB  - Type 1 diabetes (T1D) is an immune-mediated disease with a strong genetic basis
      but might be influenced by non-genetic factors such as microbiome development
      that "programs" the immune system during early life as well. Factors influencing
      pathogenesis, including a leaky intestinal mucosal barrier, an aberrant gut
      microbiota composition, and altered immune responsiveness, offer potential
      targets for prevention and/or treatment of T1D through nutritional or
      pharmacologic means. In this review, nutritional approaches during early life in
      order to protect against T1D development have been discussed. The critical role
      of tolerogenic dendritic cells in central and peripheral tolerance has been
      emphasized. In addition, since the gut microbiota affects the development of T1D
      through short-chain fatty acid (SCFA)-dependent mechanisms, we hypothesize that
      nutritional intervention boosting SCFA production may be used as a novel
      prevention strategy. Current retrospective evidence has suggested that exclusive
      and prolonged breastfeeding might play a protective role against the development
      of T1D. The beneficial properties of human milk are possibly attributed to its
      bioactive components such as unique immune-modulatory components human milk
      oligosaccharides and metabolites derived thereof, including SCFAs. These
      components might play a key role in healthy immune development and creating a fit
      and resilient immune system in early and later life.

PMID- 29033936
TI  - Coinhibitory Receptor Expression and Immune Checkpoint Blockade: Maintaining a
      Balance in CD8+ T Cell Responses to Chronic Viral Infections and Cancer.
AB  - In cancer and chronic viral infections, T cells are exposed to persistent antigen
      stimulation. This results in expression of multiple inhibitory receptors also
      called "immune checkpoints" by T cells. Although these inhibitory receptors under
      normal conditions maintain self-tolerance and prevent immunopathology, their
      sustained expression deteriorates T cell function: a phenomenon called
      exhaustion. Recent advances in cancer immunotherapy involve blockade of cytotoxic
      T lymphocyte antigen-4 and programmed cell death 1 in order to reverse T cell
      exhaustion and reinvigorate immunity, which has translated to dramatic clinical
      remission in many cases of metastatic melanoma and lung cancer. With the paucity
      of therapeutic vaccines against chronic infections such as HIV, HPV, hepatitis B,
      and hepatitis C, such adjunct checkpoint blockade strategies are required
      including the blockade of other inhibitory receptors such as T cell
      immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based
      inhibitory motif domains, T cell Ig and mucin-domain containing-3, lymphocyte
      activation gene 3, and V-domain Ig-containing suppressor of T cell activation.
      The nature of different chronic viral infections and cancers is likely to
      influence the level, composition, and pattern of inhibitory receptors expressed
      by responding T cells. This will have implications for checkpoint antibody
      blockade strategies employed for treating tumors and chronic viral infections.
      Here, we review recent advances that provide a clearer insight into the role of
      coinhibitory receptor expression in T cell exhaustion and reveal novel antibody
      blockade therapeutic targets for chronic viral infections and cancer.
      Understanding the mechanism of T cell exhaustion in response to chronic virus
      infections and cancer as well as the nature of restored T cell responses will
      contribute to further improvement of immune checkpoint blockade strategies.

PMID- 29033939
TI  - Induction of Apoptosis and Subsequent Phagocytosis of Virus-Infected Cells As an
      Antiviral Mechanism.
AB  - Viruses are infectious entities that hijack host replication machineries to
      produce their progeny, resulting, in most cases, in disease and, sometimes, in
      death in infected host organisms. Hosts are equipped with an array of defense
      mechanisms that span from innate to adaptive as well as from humoral to cellular
      immune responses. We previously demonstrated that mouse cells underwent apoptosis
      in response to influenza virus infection. These apoptotic, virus-infected cells
      were then targeted for engulfment by macrophages and neutrophils. We more
      recently reported similar findings in the fruit fly Drosophila melanogaster,
      which lacks adaptive immunity, after an infection with Drosophila C virus. In
      these experiments, the inhibition of phagocytosis led to severe influenza
      pathologies in mice and early death in Drosophila. Therefore, the induction of
      apoptosis and subsequent phagocytosis of virus-infected cells appear to be an
      antiviral innate immune mechanism that is conserved among multicellular
      organisms. We herein discuss the underlying mechanisms and significance of the
      apoptosis-dependent phagocytosis of virus-infected cells. Investigations on the
      molecular and cellular features responsible for this underrepresented virus-host
      interaction may provide a promising avenue for the discovery of novel substances
      that are targeted in medical treatments against virus-induced intractable
      diseases.

PMID- 29033940
TI  - PI3Kdelta Inhibition Enhances the Antitumor Fitness of Adoptively Transferred
      CD8+ T Cells.
AB  - Phosphatidylinositol-3-kinase p110delta (PI3Kdelta) inhibition by Idelalisib (CAL
      101) in hematological malignancies directly induces apoptosis in cancer cells and
      disrupts immunological tolerance by depleting regulatory T cells. Yet, little is
      known about the direct impact of PI3Kdelta blockade on effector T cells from CAL
      101 therapy. Herein, we demonstrate a direct effect of p110delta inactivation via
      CAL-101 on murine and human CD8+ T cells that promotes a strong undifferentiated
      phenotype (elevated CD62L/CCR7, CD127, and Tcf7). These CAL-101 T cells also
      persisted longer after transfer into tumor bearing mice in both the murine
      syngeneic and human xenograft mouse models. The less differentiated phenotype and
      improved engraftment of CAL-101 T cells resulted in stronger antitumor immunity
      compared to traditionally expanded CD8+ T cells in both tumor models. Thus, this
      report describes a novel direct enhancement of CD8+ T cells by a p110delta
      inhibitor that leads to markedly improved tumor regression. This finding has
      significant implications to improve outcomes from next generation cancer
      immunotherapies.

PMID- 29033941
TI  - Functional Analysis of Phagocyte Activity in Whole Blood from HIV/Tuberculosis
      Infected Individuals Using a Novel Flow Cytometry-Based Assay.
AB  - The accurate assessment of immune competence through ex vivo analysis is
      paramount to our understanding of those immune mechanisms that lead to protection
      or susceptibility against a broad range of human pathogens. We have developed a
      flow cytometry-based, whole blood phagocyte functional assay that utilizes the
      inflammatory inducer zymosan, coupled to OxyBURST-SE, a fluorescent reporter of
      phagosomal oxidase activity. The assay measures both phagocytic uptake and the
      superoxide burst in the phagocyte populations in whole blood. We utilized this
      assay to demonstrate impaired superoxide burst activity in the phagocytes of
      hospitalized HIV-positive patients with laboratory-confirmed tuberculosis. These
      data validate the use of the assay to assess the immune competence of patients in
      a clinical setting. The method is highly reproducible with minimal
      intraindividual variation and opens opportunities for the rapid assessment of
      cellular immune competence in peripheral blood in a disease setting.

PMID- 29033942
TI  - Mucosal Administration of Cycle-Di-Nucleotide-Adjuvanted Virosomes Efficiently
      Induces Protection against Influenza H5N1 in Mice.
AB  - The need for more effective influenza vaccines is highlighted by the emergence of
      novel influenza strains, which can lead to new pandemics. There is a growing
      population of susceptible subjects at risk for severe complications of influenza,
      such as the elderly who are only in part protected by current licensed seasonal
      vaccines. One strategy for improving seasonal and pandemic vaccines takes
      advantage of adjuvants to boost and modulate evoked immune responses. In this
      study, we examined the capacity of the recently described adjuvant cyclic di
      adenosine monophosphate (c-di-AMP) to serve as an adjuvant for improved mucosal
      influenza vaccines, and induce effective protection against influenza H5N1. In
      detail, c-di-AMP promoted (i) effective local and systemic humoral immune
      responses, including protective hemagglutination inhibition titers, (ii)
      effective cellular responses, including multifunctional T cell activity, (iii)
      induction of long-lasting immunity, and (iv) protection against viral challenge.
      Furthermore, we demonstrated the dose-sparing capacity of the adjuvant as well as
      the ability to evoke cross-clade protective immune responses. Overall, our
      results suggest that c-di-AMP contributes to the generation of a protective cell
      mediated immune response required for efficacious vaccination against influenza,
      which supports the further development of c-di-AMP as an adjuvant for seasonal
      and pandemic influenza mucosal vaccines.

PMID- 29033943
TI  - Human Immunodeficiency Virus 1 and Type I Interferons-Where Sex Makes a
      Difference.
AB  - The human immunodeficiency virus (HIV)-1 epidemic continues to represent a global
      health problem that is over-proportionally affecting women from sub-Saharan
      Africa. Besides social and environmental factors, the modulation of immunological
      pathways by sex hormones and gene dosage effects of X chromosomal-encoded genes
      have been suggested to lead to differential outcomes in HIV-1 disease. Women
      present with lower HIV-1 loads early in infection. However, the progression to
      AIDS for the same level of viremia is faster in women than in men. Type I
      interferons (IFNs) play a prominent role in the control of HIV-1 transmission and
      replication. Continuous stimulation of type I IFNs in chronic viral infections
      can lead to increased levels of immune activation, which can be higher in HIV-1
      infected women than in men. A role of steroid hormone signaling in regulating
      viral replication has been postulated, which might further account for sex
      differences observed in HIV-1 infections. Here, we review recent findings and
      current knowledge on sex-specific differences in HIV-1 infections.

PMID- 29033945
TI  - Improved Efficacy of Oral Immunotherapy Using Non-Digestible Oligosaccharides in
      a Murine Cow's Milk Allergy Model: A Potential Role for Foxp3+ Regulatory T
      Cells.
AB  - BACKGROUND: Oral immunotherapy (OIT) is a promising therapeutic approach to treat
      food allergic patients. However, there are some concerns regarding its safety and
      long-term efficacy. The use of non-digestible oligosaccharides might improve OIT
      efficacy since they are known to directly modulate intestinal epithelial and
      immune cells in addition to acting as prebiotics. AIM: To investigate whether a
      diet supplemented with plant-derived fructo-oligosaccharides (FOS) supports the
      efficacy of OIT in a murine cow's milk allergy model and to elucidate the
      potential mechanisms involved. METHODS: After oral sensitization to the cow's
      milk protein whey, female C3H/HeOuJ mice were fed either a control diet or a diet
      supplemented with FOS (1% w/w) and received OIT (10 mg whey) 5 days a week for 3
      weeks by gavage. Intradermal (i.d.) and intragastric (i.g.) challenges were
      performed to measure acute allergic symptoms and mast cell degranulation. Blood
      and organs were collected to measure antibody levels and T cell and dendritic
      cell populations. Spleen-derived T cell fractions (whole spleen- and CD25
      depleted) were transferred to naive recipient mice to confirm the involvement of
      regulatory T cells (Tregs) in allergy protection induced by OIT + FOS. RESULTS:
      OIT + FOS decreased acute allergic symptoms and mast cell degranulation upon
      challenge and prevented the challenge-induced increase in whey-specific IgE as
      observed in sensitized mice. Early induction of Tregs in the mesenteric lymph
      nodes (MLN) of OIT + FOS mice coincided with reduced T cell responsiveness in
      splenocyte cultures. CD25 depletion in OIT + FOS-derived splenocyte suspensions
      prior to transfer abolished protection against signs of anaphylaxis in
      recipients. OIT + FOS increased serum galectin-9 levels. No differences in short
      chain fatty acid (SCFA) levels in the cecum were observed between the treatment
      groups. Concisely, FOS supplementation significantly improved OIT in the acute
      allergic skin response, %Foxp3+ Tregs and %LAP+ Th3 cells in MLN, and serum
      galectin-9 levels. CONCLUSION: FOS supplementation improved the efficacy of OIT
      in cow's milk allergic mice. Increased levels of Tregs in the MLN and abolished
      protection against signs of anaphylaxis upon transfer of CD25-depleted cell
      fractions, suggest a role for Foxp3+ Tregs in the protective effect of OIT + FOS.

PMID- 29033944
TI  - Artificial Polysialic Acid Chains as Sialidase-Resistant Molecular-Anchors to
      Accumulate Particles on Neutrophil Extracellular Traps.
AB  - Neutrophils are involved in numerous immunological events. One mechanism of
      neutrophils to combat pathogens is the formation of neutrophil extracellular
      traps (NETs). Thereby, neutrophils use DNA fibers to form a meshwork of DNA and
      histones as well as several antimicrobial components to trap and kill invaders.
      However, the formation of NETs can lead to pathological conditions triggering
      among other things (e.g., sepsis or acute lung failure), which is mainly a
      consequence of the cytotoxic characteristics of accumulated extracellular
      histones. Interestingly, the carbohydrate polysialic acid represents a naturally
      occurring antagonist of the cytotoxic properties of extracellular histones.
      Inspired by polysialylated vesicles, we developed polysialylated nanoparticles.
      Since sialidases are frequently present in areas of NET formation, we protected
      the sensitive non-reducing end of these homopolymers. To this end, the terminal
      sialic acid residue of the non-reducing end was oxidized and directly coupled to
      nanoparticles. The covalently linked sialidase-resistant polysialic acid chains
      are still able to neutralize histone-mediated cytotoxicity and to initiate
      binding of these polysialylated particles to NET filaments. Furthermore,
      polysialylated fluorescent microspheres can be used as a bioanalytical tool to
      stain NET fibers. Thus, polySia chains might not only be a useful agent to reduce
      histone-mediated cytotoxicity but also an anchor to accumulate nanoparticles
      loaded with active substances in areas of NET formation.

PMID- 29033946
TI  - Exploitation of Scavenger Receptor, Macrophage Receptor with Collagenous
      Structure, by Cryptococcus neoformans Promotes Alternative Activation of
      Pulmonary Lymph Node CD11b+ Conventional Dendritic Cells and Non-Protective Th2
      Bias.
AB  - Macrophage receptor with collagenous structure (MARCO) contributes to fungal
      containment during the early/innate phase of cryptococcal infection; however, its
      role in adaptive antifungal immunity remains unknown. Using a murine model of
      cryptococcosis, we compared host adaptive immune responses in wild-type and MARCO
      /- mice throughout an extended time course post-infection. Unlike in early
      infection, MARCO deficiency resulted in improved pulmonary fungal clearance and
      diminished cryptococcal dissemination during the efferent phase. Improved fungal
      control in the absence of MARCO expression was associated with enhanced hallmarks
      of protective Th1-immunity, including higher frequency of pulmonary TNF-alpha
      producing T cells, increased cryptococcal-antigen-triggered IFN-gamma and TNF
      alpha production by splenocytes, and enhanced expression of M1 polarization genes
      by pulmonary macrophages. Concurrently, we found lower frequencies of IL-5- and
      IL-13-producing T cells in the lungs, impaired production of IL-4 and IL-10 by
      cryptococcal antigen-pulsed splenocytes, and diminished serum IgE, which were
      hallmarks of profoundly suppressed efferent Th2 responses in MARCO-deficient mice
      compared to WT mice. Mechanistically, we found that MARCO expression facilitated
      early accumulation and alternative activation of CD11b+ conventional DC (cDC) in
      the lung-associated lymph nodes (LALNs), which contributed to the progressive
      shift of the immune response from Th1 toward Th2 at the priming site (LALNs) and
      local infection site (lungs) during the efferent phase of cryptococcal infection.
      Taken together, our study shows that MARCO can be exploited by the fungal
      pathogen to promote accumulation and alternative activation of CD11b+ cDC in the
      LALN, which in turn alters Th1/Th2 balance to promote fungal persistence and
      dissemination.

PMID- 29033947
TI  - Interferon-lambdas: Front-Line Guardians of Immunity and Homeostasis in the
      Respiratory Tract.
AB  - Type III interferons (IFNs), also termed lambda IFNs (IFNlambdas) or interleukins
      28/29, constitute a new addition to the IFN family. They are induced upon
      infection and are particularly abundant at barrier surfaces, such as the
      respiratory and gastrointestinal tracts. Although they signal through a unique
      heterodimeric receptor complex comprising IFNLR1 and IL10RB, they activate a
      downstream signaling pathway remarkably similar to that of type I IFNs and share
      many functions with them. Yet, they also have important differences which are
      only now starting to unfold. Here, we review the current literature implicating
      type III IFNs in the regulation of immunity and homeostasis in the respiratory
      tract. We survey the common and unique characteristics of type III IFNs in terms
      of expression patterns, cellular targets, and biological activities and discuss
      their emerging role in first line defenses against respiratory viral infections.
      We further explore their immune modulatory functions and their involvement in the
      regulation of inflammatory responses during chronic respiratory diseases, such as
      asthma and chronic obstructive pulmonary disease. Type III IFNs are, therefore,
      arising as front-line guardians of immune defenses in the respiratory tract, fine
      tuning inflammation, and as potential novel therapeutics for the treatment of
      diverse respiratory diseases, including influenza virus infection and asthma.

PMID- 29033948
TI  - Unique Features of Pancreatic-Resident Regulatory T Cells in Autoimmune Type 1
      Diabetes.
AB  - Recent progress in regulatory T cells (Tregs) biology emphasizes the importance
      of understanding tissue-resident Tregs in response to tissue-specific
      environment. Now, emerging evidence suggests that pancreatic-resident forkhead
      box P3+ Tregs have distinguishable effects on the suppression of over-exuberant
      immune responses in autoimmune type 1 diabetes (T1D). Thus, there is growing
      interest in elucidating the role of pancreatic-resident Tregs that function and
      evolve in the local environment. In this review, we discuss the phenotype and
      function of Tregs residing in pancreatic tissues and pancreatic lymph nodes, with
      emphasis on the unique subpopulations of Tregs that control the disease
      progression in the context of T1D. Specifically, we discuss known and possible
      modulators that influence the survival, migration, and maintenance of pancreatic
      Tregs.

PMID- 29033949
TI  - Microarray Analysis Identifies the Potential Role of Long Non-Coding RNA in
      Regulating Neuroinflammation during Japanese Encephalitis Virus Infection.
AB  - Japanese encephalitis virus (JEV) is the leading cause of epidemic encephalitis
      worldwide. JEV-induced neuroinflammation is characterized by profound neuronal
      cells damage accompanied by activation of glial cells. Albeit long non-coding
      RNAs (lncRNAs) have been emerged as important regulatory RNAs with profound
      effects on various biological processes, it is unknown how lncRNAs regulate JEV
      induced inflammation. Here, using microarray approach, we identified 618 lncRNAs
      and 1,007 mRNAs differentially expressed in JEV-infected mice brain. The
      functional annotation analysis revealed that differentially regulated transcripts
      were predominantly involved in various signaling pathways related to host immune
      and inflammatory responses. The lncRNAs with their potential to regulate JEV
      induced inflammatory response were identified by constructing the lncRNA-mRNA
      coexpression network. Furthermore, silencing of the two selected lncRNAs (E52329
      and N54010) resulted in reducing the phosphorylation of JNK and MKK4, which are
      known to be involved during inflammatory response. Collectively, we first
      demonstrated the transcriptomic landscape of lncRNAs in mice brain infected with
      JEV and analyzed the coexpression network of differentially regulated lncRNAs and
      mRNAs during JEV infection. Our results provide a better understanding of the
      host response to JEV infection and suggest that the identified lncRNAs may be
      used as potential therapeutic targets for the management of Japanese
      encephalitis.

PMID- 29033950
TI  - Glutathione Fine-Tunes the Innate Immune Response toward Antiviral Pathways in a
      Macrophage Cell Line Independently of Its Antioxidant Properties.
AB  - Glutathione (GSH), a major cellular antioxidant, is considered an inhibitor of
      the inflammatory response involving reactive oxygen species (ROS). However,
      evidence is largely based on experiments with exogenously added
      antioxidants/reducing agents or pro-oxidants. We show that depleting macrophages
      of 99% of GSH does not exacerbate the inflammatory gene expression profile in the
      RAW264 macrophage cell line or increase expression of inflammatory cytokines in
      response to the toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS);
      only two small patterns of LPS-induced genes were sensitive to GSH depletion. One
      group, mapping to innate immunity and antiviral responses (Oas2, Oas3, Mx2, Irf7,
      Irf9, STAT1, il1b), required GSH for optimal induction. Consequently, GSH
      depletion prevented the LPS-induced activation of antiviral response and its
      inhibition of influenza virus infection. LPS induction of a second group of genes
      (Prdx1, Srxn1, Hmox1, GSH synthase, cysteine transporters), mapping to nrf2 and
      the oxidative stress response, was increased by GSH depletion. We conclude that
      the main function of endogenous GSH is not to limit inflammation but to fine-tune
      the innate immune response to infection.

PMID- 29033951
TI  - Sphingosine-1-Phosphate Receptor 5 Modulates Early-Stage Processes during
      Fibrogenesis in a Mouse Model of Systemic Sclerosis: A Pilot Study.
AB  - Systemic sclerosis (SSc) is a rare multi-organ autoimmune disease characterized
      by progressive skin fibrosis. Inflammation, type 2 immunity, and fibrogenic
      processes are involved in disease development and may be affected by
      sphingolipids. However, details about early-stage pathophysiological mechanisms
      and implicated mediators remain elusive. The sphingolipid sphingosine-1-phosphate
      (S1P) is elevated in the sera of SSc patients, and its receptor S1P5 is expressed
      in skin tissue. Nevertheless, almost nothing is known about the dermatological
      contribution of S1P5 to inflammatory and pro-fibrotic processes leading to the
      pathological changes seen in SSc. In this study, we observed a novel effect of
      S1P5 on the inflammatory processes during low-dose bleomycin (BLM)-induced
      fibrogenesis in murine skin. By comparing 2-week-treated skin areas of wild-type
      (WT) and S1P5-deficient mice, we found that S1P5 is important for the
      transcriptional upregulation of the Th2 characteristic transcription factor GATA
      3 under treatment-induced inflammatory conditions, while T-bet (Th1) and FoxP3
      (Treg) mRNA expression was regulated independently of S1P5. Additionally,
      treatment caused a regulation of S1P receptor 1 and S1P receptor 3 mRNA as well
      as a regulation of long-chain ceramide profiles, which both differ significantly
      between the genotypes. Despite S1P5-dependent differences regarding inflammatory
      processes, similar macroscopic evidence of fibrosis was detected in the skin
      histology of WT and S1P5-deficient mice after 4 weeks of subcutaneous BLM
      treatment. However, at the earlier 2-week point in time, the mRNA data of pro
      collagen type 1 and SMAD7 indicate a pro-fibrotic S1P5 contribution in the
      applied SSc mouse model. In conclusion, we propose that S1P5 plays a role as a
      novel modulator during the early phase of BLM-caused fibrogenesis in murine skin.
      An immediate relationship between dermal S1P5 expression and fibrotic processes
      leading to skin alterations, such as formative for SSc pathogenesis, is indicated
      but should be studied more profound in further investigations. Therefore, this
      study is an initial step in understanding the role of S1P5-mediated effects
      during early stages of fibrogenesis, which may encourage the ongoing search for
      new therapeutic options for SSc patients.

PMID- 29033952
TI  - Essential Role for Ethanolamine Plasmalogen Hydrolysis in Bacterial
      Lipopolysaccharide Priming of Macrophages for Enhanced Arachidonic Acid Release.
AB  - Due to their high content in esterified arachidonic acid (AA), macrophages
      provide large amounts of eicosanoids during innate immune reactions. Bacterial
      lipopolysaccharide (LPS) is a poor trigger of AA mobilization in macrophages but
      does have the capacity to prime these cells for greatly increased AA release upon
      subsequent stimulation. In this work, we have studied molecular mechanisms
      underlying this phenomenon. By using mass spectrometry-based lipidomic analyses,
      we show in this work that LPS-primed zymosan-stimulated macrophages exhibit an
      elevated consumption of a particular phospholipid species, i.e., the ethanolamine
      plasmalogens, which results from reduced remodeling of phospholipids via coenzyme
      A-independent transacylation reactions. Importantly however, LPS-primed
      macrophages show no changes in their capacity to directly incorporate AA into
      phospholipids via CoA-dependent acylation reactions. The essential role for
      ethanolamine plasmalogen hydrolysis in LPS priming is further demonstrated by the
      use of plasmalogen-deficient cells. These cells, while responding normally to
      zymosan by releasing quantities of AA similar to those released by cells
      expressing normal plasmalogen levels under the same conditions, fail to show an
      LPS-primed response to the same stimulus, thus unambiguously demonstrating a
      cause-effect relationship between LPS priming and plasmalogen hydrolysis.
      Collectively, these results suggest a hitherto unrecognized role for ethanolamine
      plasmalogen hydrolysis and CoA-independent transacylation reactions in modulating
      the eicosanoid biosynthetic response.

PMID- 29033953
TI  - Development and Characterization of Transgenic Sugarcane with Insect Resistance
      and Herbicide Tolerance.
AB  - Genetically modified crops which had been commercial applied extensively majorly
      are the insect resistance and herbicide tolerance events. In this study, the Bt
      insecticidal gene Cry1Ab, the glyphosate-tolerant gene EPSPS, and the selection
      marker gene PMI were combined into a single transferred DNA fragment and
      introduced into sugarcane by Agrobacterium-mediated transformation. Thirty-three
      resistant plantlets were obtained after selection using a PMI/mannose selection
      system. Thirty of these resistant plantlets were PCR positive for the three
      target genes. Southern blot assay revealed that the copy number of the integrated
      fragment in the transformed plantlets varied from 1 to 7. ELISA analysis showed
      that 23 of the 33 resistant plantlets expressed Cry1Ab and EPSPS protein. Five
      single-copy and ELISA-positive transgenic lines were tested under laboratory and
      field conditions to determine their resistance to insects and herbicides, and
      also evaluated their agronomic characteristics and industrial traits. Results
      showed that larvae fed with fodder mixture containing stem tissues from single
      copy transgenic lines were weak and small, moreover, pupation and eclosion were
      delayed significantly during voluntary feeding bioassays. None of transgenic
      sugarcane was destroyed by cane borer while more than 30% of wild type sugarcane
      was destroyed by cane borer. For herbicide resistance, the transgenic plantlets
      grew healthy even when treated with up to 0.5% roundup while wild type plantlets
      would die off when treated with 0.1% roundup. Thus demonstrate that these
      transgenic lines showed strong insect resistance and glyphosate tolerance under
      both laboratory and field conditions. But in the field most of the transgenic
      plants were shorter and more slender than non-transformed control plants. So they
      presented poor agronomic characteristics and industrial traits than non
      transformed control plants. Thus, a considerable number of embryogenic calli
      should be infected to obtain transgenic lines with potential for commercial use.

PMID- 29033954
TI  - Setaria Comes of Age: Meeting Report on the Second International Setaria Genetics
      Conference.
AB  - Setaria viridis is an emerging model for cereal and bioenergy grasses because of
      its short stature, rapid life cycle and expanding genetic and genomic toolkits.
      Its close phylogenetic relationship with economically important crops such as
      maize and sorghum positions Setaria as an ideal model system for accelerating
      discovery and characterization of crop genes that control agronomically important
      traits. The Second International Setaria Genetics Conference was held on March 6
      8, 2017 at the Donald Danforth Plant Science Center, St. Louis, MO, United States
      to discuss recent technological breakthroughs and research directions in Setaria
      (presentation abstracts can be downloaded at
      https://www.brutnelllab.org/setaria). Here, we highlight topics presented in the
      conference including inflorescence architecture, C4 photosynthesis and abiotic
      stress. Genetic and genomic toolsets including germplasm, mutant populations,
      transformation and gene editing technologies are also discussed. Since the last
      meeting in 2014, the Setaria community has matured greatly in the quality of
      research being conducted. Outreach and increased communication with maize and
      other plant communities will allow broader adoption of Setaria as a model system
      to translate fundamental discovery research to crop improvement.

PMID- 29033956
TI  - Transcriptome and Differential Expression Profiling Analysis of the Mechanism of
      Ca2+ Regulation in Peanut (Arachis hypogaea) Pod Development.
AB  - Calcium not only serves as a necessary nutrient for plant growth but also acts as
      a ubiquitous central hub in a large number of signaling pathways. Free Ca2+
      deficiency in the soil may cause early embryo abortion, which eventually led to
      abnormal development of peanut pod during the harvest season. To understand the
      mechanisms of Ca2+ regulation in pod development, transcriptome analysis of
      peanut gynophores and pods was performed by comparing the treatments between free
      Ca2+ sufficiency and free Ca2+ deficiency using Illumina HiSeqTM 2000.
      9,903,082,800 nt bases are generated totally. After assembly, the average length
      of 102,819 unigenes is 999 nt, N50 is 1,782 nt. RNA-seq based gene expression
      profilings showed a large number of genes at the transcriptional level changed
      significantly between the aerial pegs and underground swelling pods under free
      Ca2+ sufficienct or deficiency treatments, respectively. Genes encoding key
      members of Ca2+ signaling transduction pathway, enzymes for hormone metabolism,
      cell division and growth, transcriptional factor as well as embryo development
      were highlighted. This information provides useful information for our further
      study. The results of digital gene expression (DGE) indicated that exogenous
      calcium might contribute to the development of peanut pod through its signal
      transduction pathway, meanwhile, promote the normal transition of the gynophores
      to the reproductive development.

PMID- 29033957
TI  - Reacquisition of New Meristematic Sites Determines the Development of a New
      Organ, the Cecidomyiidae Gall on Copaifera langsdorffii Desf. (Fabaceae).
AB  - The development of gall shapes has been attributed to the feeding behavior of the
      galling insects and how the host tissues react to galling stimuli, which
      ultimately culminate in a variable set of structural responses. A superhost of
      galling herbivores, Copaifera langsdorffii, hosts a bizarre "horn-shaped" leaflet
      gall morphotype induced by an unidentified species of Diptera: Cecidomyiidae. By
      studying the development of this gall morphotype under the anatomical and
      physiological perspectives, we demonstrate the symptoms of the Cecidomyiidae
      manipulation over plant tissues, toward the cell redifferentiation and tissue
      neoformation. The most prominent feature of this gall is the shifting in shape
      from growth and development phase toward maturation, which imply in metabolites
      accumulation detected by histochemical tests in meristem-like group of cells
      within gall structure. We hypothesize that the development of complex galls, such
      as the horn-shaped demands the reacquisition of cell meristematic competence.
      Also, as mature galls are green, their photosynthetic activity should be
      sufficient for their oxygenation, thus compensating the low gas diffusion through
      the compacted gall parenchyma. We currently conclude that the galling
      Cecidomyiidae triggers the establishment of new sites of meristematic tissues,
      which are ultimately responsible for shifting from the young conical to the
      mature horn-shaped gall morphotype. Accordingly, the conservative photosynthesis
      activity in gall site maintains tissue homeostasis by avoiding hypoxia and
      hipercarbia in the highly compacted gall tissues.

PMID- 29033959
TI  - Editorial: Advances in Plant-Hemipteran Interactions.

PMID- 29033958
TI  - Enhanced Bacterial Wilt Resistance in Potato Through Expression of Arabidopsis
      EFR and Introgression of Quantitative Resistance from Solanum commersonii.
AB  - Bacterial wilt (BW) caused by Ralstonia solanacearum is responsible for
      substantial losses in cultivated potato (Solanum tuberosum) crops worldwide.
      Resistance genes have been identified in wild species; however, introduction of
      these through classical breeding has achieved only partial resistance, which has
      been linked to poor agronomic performance. The Arabidopsis thaliana (At) pattern
      recognition receptor elongation factor-Tu (EF-Tu) receptor (EFR) recognizes the
      bacterial pathogen-associated molecular pattern EF-Tu (and its derived peptide
      elf18) to confer anti-bacterial immunity. Previous work has shown that transfer
      of AtEFR into tomato confers increased resistance to R. solanacearum. Here, we
      evaluated whether the transgenic expression of AtEFR would similarly increase BW
      resistance in a commercial potato line (INIA Ipora), as well as in a breeding
      potato line (09509.6) in which quantitative resistance has been introgressed from
      the wild potato relative Solanum commersonii. Resistance to R. solanacearum was
      evaluated by damaged root inoculation under controlled conditions. Both INIA
      Ipora and 09509.6 potato lines expressing AtEFR showed greater resistance to R.
      solanacearum, with no detectable bacteria in tubers evaluated by multiplex-PCR
      and plate counting. Notably, AtEFR expression and the introgression of
      quantitative resistance from S. commersonii had a significant additive effect in
      09509.6-AtEFR lines. These results show that the combination of heterologous
      expression of AtEFR with quantitative resistance introgressed from wild relatives
      is a promising strategy to develop BW resistance in potato.

PMID- 29033960
TI  - Evaluation of the CropSyst Model during Wheat-Maize Rotations on the North China
      Plain for Identifying Soil Evaporation Losses.
AB  - The North China Plain (NCP) is a major grain production zone that plays a
      critical role in ensuring China's food supply. Irrigation is commonly used during
      grain production; however, the high annual water deficit [precipitation (P) minus
      evapotranspiration (ET)] in typical irrigated cropland does not support double
      cropping systems (such as maize and wheat) and this has resulted in the steep
      decline in the water table (~0.8 m year-1 at the Luancheng station) that has
      taken place since the 1970s. The current study aimed to adapt and check the
      ability of the CropSyst model (Suite-4) to simulate actual evapotranspiration
      (ETa), biomass, and grain yield, and to identify major evaporation (E) losses
      from winter wheat (WW) and summer maize (SM) rotations. Field experiments were
      conducted at the Luancheng Agro-ecosystem station, NCP, in 2010-2011 to 2012
      2013. The CropSyst model was calibrated on wheat/maize (from weekly leaf
      area/biomass data available for 2012-2013) and validated onto measured ETa,
      biomass, and grain yield at the experimental station from 2010-2011 to 2011-2012,
      by using model calibration parameters. The revalidation was performed with the
      ETa, biomass, grain yield, and simulated ETa partition for 2008-2009 WW [ETa
      partition was measured by the Micro-lysimeter (MLM) and isotopes approach
      available for this year]. For the WW crop, E was 30% of total ETa; but from 2010
      11 to 2013, the annual average E was ~40% of ETa for the WW and SM rotation.
      Furthermore, the WW and SM rotation from 2010-2011 to 2012-2013 was divided into
      three growth periods; (i) pre-sowing irrigation (PSI; sowing at field capacity)
      to emergence period (EP), (ii) EP to canopy cover period (CC) and (iii) CC to
      harvesting period (HP), and E from each growth period was ~10, 60, and 30%,
      respectively. In general, error statistics such as RMSE, Willmott's d, and NRMSE
      in the model evaluation for wheat ETa (maize ETa) were 38.3 mm, 0.81, and 9.24%
      (31.74 mm, 0.73, and 11.89%); for wheat biomass (maize biomass) they were 1.25 Mg
      ha-1, 0.83, and 9.64% (0.78 Mg ha-1, 0.96, and 7.96%); and for wheat grain yield
      (maize grain yield) they were 0.65 Mg ha-1, 0.82, and 9.87% (0.2 Mg ha-1, 0.99,
      and 3.79%). The results showed that CropSyst is a valid model that can be use
      with a reliable degree of accuracy for optimizing WW and SM grain yield
      production and water requirement on the NCP.

PMID- 29033961
TI  - Fast High Resolution Volume Carving for 3D Plant Shoot Reconstruction.
AB  - Volume carving is a well established method for visual hull reconstruction and
      has been successfully applied in plant phenotyping, especially for 3d
      reconstruction of small plants and seeds. When imaging larger plants at still
      relatively high spatial resolution (<=1 mm), well known implementations become
      slow or have prohibitively large memory needs. Here we present and evaluate a
      computationally efficient algorithm for volume carving, allowing e.g., 3D
      reconstruction of plant shoots. It combines a well-known multi-grid
      representation called "Octree" with an efficient image region integration scheme
      called "Integral image." Speedup with respect to less efficient octree
      implementations is about 2 orders of magnitude, due to the introduced refinement
      strategy "Mark and refine." Speedup is about a factor 1.6 compared to a highly
      optimized GPU implementation using equidistant voxel grids, even without using
      any parallelization. We demonstrate the application of this method for trait
      derivation of banana and maize plants.

PMID- 29033955
TI  - Multilevel Regulation of Abiotic Stress Responses in Plants.
AB  - The sessile lifestyle of plants requires them to cope with stresses in situ.
      Plants overcome abiotic stresses by altering structure/morphology, and in some
      extreme conditions, by compressing the life cycle to survive the stresses in the
      form of seeds. Genetic and molecular studies have uncovered complex regulatory
      processes that coordinate stress adaptation and tolerance in plants, which are
      integrated at various levels. Investigating natural variation in stress responses
      has provided important insights into the evolutionary processes that shape the
      integrated regulation of adaptation and tolerance. This review primarily focuses
      on the current understanding of how transcriptional, post-transcriptional, post
      translational, and epigenetic processes along with genetic variation orchestrate
      stress responses in plants. We also discuss the current and future development of
      computational tools to identify biologically meaningful factors from high
      dimensional, genome-scale data and construct the signaling networks consisting of
      these components.

PMID- 29033964
TI  - Management of Fruit Species in Urban Home Gardens of Argentina Atlantic Forest as
      an Influence for Landscape Domestication.
AB  - Home gardens are considered germplasm repositories and places for
      experimentation, thus they are key sites for the domestication of plants.
      Domestication is considered a constant process that occurs along a continuum from
      wild to managed to domesticated populations. Management may lead to the
      modification of populations and in other cases to their distribution, changing
      population structure in a landscape. Our objective is focused on the management
      received in home gardens by perennial species of fruits. For this, the management
      practices applied to native and exotic perennial fruits species by a group of 20
      women in the periurban zone of Iguazu, Argentina, were analyzed. In-depth
      interviews were conducted, as well as guided tours for the recognition and
      collection of specimens of species and ethnovarieties. Sixty-six fruit species
      managed in the home gardens were recorded. The predominant families are Rutaceae,
      Myrtaceae, and Rosaceae. The fruit species with the highest number of associated
      management practices are pitanga (Eugenia uniflora) and pindo (Syagrus
      rommanzoffiana). The 10 species with the highest management intensity are (in
      decreasing order of intensity) banana (Musa x paradisiaca), palta (Persea
      americana), pitanga (E. uniflora), mango (Mangifera indica), cocu (Allophylus
      edulis), mamon (Carica papaya), guayaba (Psidium guajava), limon mandarina
      (Citrus x taitensis), guembe (Philodendron bipinnatifidum), and mandarina (Citrus
      reticulata). Among the families with the greatest modifications in their
      distribution, abundance and presence of ethnovarieties in domestic gardens, are
      the native Myrtaceae and the exotic Rutaceae. The main management practices
      involved are cultivation, tolerance, transplant and enhancement in decreasing
      order. It can be concluded that in Iguazu, fruit species management shows both in
      plant germplasm as in environment a continuum that through tolerance, transplant
      and cultivation latu sensu has derived in a mosaic of species in different
      management situations, which in turn are representative of an anthropogenic
      landscape in constant domestication and change.

PMID- 29033962
TI  - Unveiling Chloroplast RNA Editing Events Using Next Generation Small RNA
      Sequencing Data.
AB  - Organellar RNA editing involves the modification of nucleotide sequences to
      maintain conserved protein functions, mainly by reverting non-neutral codon
      mutations. The loss of plastid editing events, resulting from mutations in RNA
      editing factors or through stress interference, leads to developmental,
      physiological and photosynthetic alterations. Recently, next generation
      sequencing technology has generated the massive discovery of sRNA sequences and
      expanded the number of sRNA data. Here, we present a method to screen chloroplast
      RNA editing using public sRNA libraries from Arabidopsis, soybean and rice. We
      mapped the sRNAs against the nuclear, mitochondrial and plastid genomes to
      confirm predicted cytosine to uracil (C-to-U) editing events and identify new
      editing sites in plastids. Among the predicted editing sites, 40.57, 34.78, and
      25.31% were confirmed using sRNAs from Arabidopsis, soybean and rice,
      respectively. SNP analysis revealed 58.2, 43.9, and 37.5% new C-to-U changes in
      the respective species and identified known and new putative adenosine to inosine
      (A-to-I) RNA editing in tRNAs. The present method and data reveal the potential
      of sRNA as a reliable source to identify new and confirm known editing sites.

PMID- 29033966
TI  - Impaired Magnesium Protoporphyrin IX Methyltransferase (ChlM) Impedes Chlorophyll
      Synthesis and Plant Growth in Rice.
AB  - Magnesium protoporphyrin IX methyltransferase (ChlM) catalyzes the formation of
      magnesium protoporphyrin IX monomethylester (MgPME) from magnesium protoporphyrin
      IX (MgP) in the chlorophyll synthesis pathway. However, no ChlM gene has yet been
      identified and studied in monocotyledonous plants. In this study, a spontaneous
      mutant, yellow-green leaf 18 (ygl18), was isolated from rice (Oryza sativa). This
      mutant showed yellow-green leaves, decreased chlorophyll level, and climate
      dependent growth differences. Map-based cloning of this mutant identified the
      YGL18 gene LOC_Os06g04150. YGL18 is expressed in green tissues, especially in
      leaf organs, where it functions in chloroplasts. YGL18 showed an amino-acid
      sequence similarity to that of ChlM from different photosynthetic organisms. In
      vitro enzymatic assays demonstrated that YGL18 performed ChlM enzymatic activity,
      but ygl18 had nearly lost all ChlM activity. Correspondingly, the substrate MgP
      was largely accumulated while the product MgPME was reduced in ygl18 leaves.
      YGL18 is required for light-dependent and photoperiod-regulated chlorophyll
      synthesis. The retarded growth of ygl18 mutant plants was caused by the high
      light intensity. Moreover, the higher light intensity and longer exposure in high
      light intensity even made the ygl18 plants be more susceptible to death. Based on
      these results, it is suggested that YGL18 plays essential roles in light-related
      chlorophyll synthesis and light intensity-involved plant growth.

PMID- 29033965
TI  - Novel Alleles of Two Tightly Linked Genes Encoding Polygalacturonase-Inhibiting
      Proteins (VrPGIP1 and VrPGIP2) Associated with the Br Locus That Confer Bruchid
      (Callosobruchus spp.) Resistance to Mungbean (Vigna radiata) Accession V2709.
AB  - Nearly all mungbean cultivars are completely susceptible to seed bruchids
      (Callosobruchus chinensis and Callosobruchus maculatus). Breeding bruchid
      resistant mungbean is a major goal in mungbean breeding programs. Recently, we
      demonstrated in mungbean (Vigna radiata) accession V2802 that VrPGIP2, which
      encodes a polygalacturonase inhibiting protein (PGIP), is the Br locus
      responsible for resistance to C. chinensis and C. maculatus. In this study,
      mapping in mungbean accession V2709 using a BC11F2 population of 355 individuals
      revealed that a single major quantitative trait locus, which controlled
      resistance to both C. chinensis and C. maculatus, was located in a 237.35 Kb
      region of mungbean chromosome 5 that contained eight annotated genes, including
      VrPGIP1 (LOC106760236) and VrPGIP2 (LOC106760237). VrPGIP1 and VrPGIP2 are
      located next to each other and are only 27.56 Kb apart. Sequencing VrPGIP1 and
      VrPGIP2 in "V2709" revealed new alleles for both VrPGIP1 and VrPGIP2, named
      VrPGIP1-1 and VrPGIP2-2, respectively. VrPGIP2-2 has one single nucleotide
      polymorphism (SNP) at position 554 of wild type VrPGIP2. This SNP is a guanine to
      cystine substitution and causes a proline to arginine change at residue 185 in
      the VrPGIP2 of "V2709". VrPGIP1-1 has 43 SNPs compared with wild type and
      "V2802", and 20 cause amino acid changes in VrPGIP1. One change is threonine to
      proline at residue 185 in VrPGIP1, which is the same as in VrPGIP2. Sequence
      alignments of VrPGIP2 and VrPGIP1 from "V2709" with common bean (Phaseolus
      vulgaris) PGIP2 revealed that residue 185 in VrPGIP2 and VrPGIP1 contributes to
      the secondary structures of proteins that affect interactions between PGIP and
      polygalacturonase, and that some amino acid changes in VrPGIP1 also affect
      interactions between PGIP and polygalacturonase. Thus, tightly linked VrPGIP1 and
      VrPGIP2 are the likely genes at the Br locus that confer bruchid resistance in
      mungbean "V2709".

PMID- 29033963
TI  - Convergent Evolution of Pathogen Effectors toward Reactive Oxygen Species
      Signaling Networks in Plants.
AB  - Microbial pathogens have evolved protein effectors to promote virulence and cause
      disease in host plants. Pathogen effectors delivered into plant cells suppress
      plant immune responses and modulate host metabolism to support the infection
      processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling
      molecules to trigger plant immune responses, such as pathogen-associated
      molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered
      immunity. In this review, we discuss recent insights into the molecular functions
      of pathogen effectors that target multiple steps in the ROS signaling pathway in
      plants. The perception of PAMPs by pattern recognition receptors leads to the
      rapid and strong production of ROS through activation of NADPH oxidase
      Respiratory Burst Oxidase Homologs (RBOHs) as well as peroxidases. Specific
      pathogen effectors directly or indirectly interact with plant nucleotide-binding
      leucine-rich repeat receptors to induce ROS production and the hypersensitive
      response in plant cells. By contrast, virulent pathogens possess effectors
      capable of suppressing plant ROS bursts in different ways during infection. PAMP
      triggered ROS bursts are suppressed by pathogen effectors that target mitogen
      activated protein kinase cascades. Moreover, pathogen effectors target vesicle
      trafficking or metabolic priming, leading to the suppression of ROS production.
      Secreted pathogen effectors block the metabolic coenzyme NADP-malic enzyme,
      inhibiting the transfer of electrons to the NADPH oxidases (RBOHs) responsible
      for ROS generation. Collectively, pathogen effectors may have evolved to converge
      on a common host protein network to suppress the common plant immune system,
      including the ROS burst and cell death response in plants.

PMID- 29033967
TI  - Photosynthetic Response of Soybean Leaf to Wide Light-Fluctuation in Maize
      Soybean Intercropping System.
AB  - In maize-soybean intercropping system, soybean plants will be affected by the
      wide light-fluctuation, which resulted from the shading by maize plants, as the
      shading of maize the light is not enough for soybean in the early morning and
      late afternoon, but at noon, the light is strong as the maize shading
      disappeared. The objective of this study is to evaluate the photosynthetic
      response of soybean leaf to the wide light-fluctuation. The data of diurnal
      variation of photosynthetic characters showed that the photosynthetic rate of
      intercropped soybean was weaker than that of monocropped soybean. The chlorophyll
      content, ratio of chlorophyll a/b, and AQE (apparent quantum efficiency) were
      increased and Rd (dark respiration rate) was decreased for the more efficient
      interception and absorption of light and carbon gain in intercropping. deltaRo
      (The efficiency/probability with which an electron from the intersystem electron
      carriers was transferred to reduce end electron acceptors at the PSI acceptor
      side) and phiRo (the quantum yield for the reduction of the end electron
      acceptors at the PSI acceptor side) in intercropped soybean leaf were lower
      compared to those in monocropped one, which showed that the acceptor side of PSI
      might be inhibited, and also it was the main reason that soybean plants showed a
      low photosynthetic capacity in intercropping. psiEo (the efficiency/probability
      with an electron moves further than QA-) in monocropping and intercropping
      decreased 5.8, and 35.7%, respectively, while phiEo (quantum yield for electron
      transport) decreased 27.7 and 45.3% under the high radiation at noon, which
      suggested that the acceptor side of PSII was inhibited, while the NPQ became
      higher. These were beneficial to dissipate excess excitation energy in time, and
      protect the photosynthetic apparatus against photo-damage. The higher performance
      index on the absorption basis (PIABS) and lower deltaRo, phiRo, psiEo, and phiEo
      of intercropped soybeans compared to monocropping under high radiation indicated
      that the electron transfer of intercropped soybean was inhibited more seriously
      and intercropped soybean adjusted the electron transport between PSII to PSI to
      adapt the light-fluctuation. Higher NPQ capacity of intercropped soybeans played
      a key role in keeping the leaf with a better physiological flexibility under the
      high radiation.

PMID- 29033969
TI  - Intercropping Induces Changes in Specific Secondary Metabolite Concentration in
      Ethiopian Kale (Brassica carinata) and African Nightshade (Solanum scabrum) under
      Controlled Conditions.
AB  - Intercropping is widespread in small-holder farming systems in tropical regions
      and is also practiced in the cultivation of indigenous vegetables, to alleviate
      the multiple burdens of malnutrition. Due to interspecific competition and/or
      complementation between intercrops, intercropping may lead to changes in plants
      accumulation of minerals and secondary metabolites and hence, alter nutritional
      quality for consumers. Intercropping aims to intensify land productivity, while
      ensuring that nutritional quality is not compromised. This study aimed to
      investigate changes in minerals and secondary plant metabolites in intercropped
      Brassica carinata and Solanum scabrum, two important African indigenous
      vegetables, and evaluated the suitability of this combination for dryer areas. B.
      carinata and S. scabrum were grown for 6 weeks under controlled conditions in a
      greenhouse trial. Large rootboxes (8000 cm3 volume) were specifically designed
      for this experiment. Each rootbox was planted with two plants, either of the same
      plant species (mono) or one of each plant species (mixed). A quartz sand/soil
      substrate was used and fertilized adequately for optimal plant growth. During the
      last 4 weeks of the experiment, the plants were either supplied with optimal (65%
      WHC) or low (30% WHC) irrigation, to test the effect of a late-season drought.
      Intercropping increased total glucosinolate content in B. carinata, while
      maintaining biomass production and the contents of other health related minerals
      in both B. carinata and S. scabrum. Moreover, low irrigation led to an increase
      in carotene accumulation in both mono and intercropped S. scabrum, but not in B.
      carinata, while the majority of kaempferol glycosides and hydroxycinnamic acid
      derivatives of both species were decreased by intercropping and drought
      treatment. This study indicates that some health-related phytochemicals can be
      modified by intercropping or late-season drought, but field validation of these
      results is necessary before definite recommendation can be made to stakeholders.

PMID- 29033971
TI  - Genetic Dissection of Root Morphological Traits Related to Nitrogen Use
      Efficiency in Brassica napus L. under Two Contrasting Nitrogen Conditions.
AB  - As the major determinant for nutrient uptake, root system architecture (RSA) has
      a massive impact on nitrogen use efficiency (NUE). However, little is known the
      molecular control of RSA as related to NUE in rapeseed. Here, a rapeseed
      recombinant inbred line population (BnaZNRIL) was used to investigate root
      morphology (RM, an important component for RSA) and NUE-related traits under high
      nitrogen (HN) and low-nitrogen (LN) conditions by hydroponics. Data analysis
      suggested that RM-related traits, particularly root size had significantly
      phenotypic correlations with plant dry biomass and N uptake irrespective of N
      levels, but no or little correlation with N utilization efficiency (NUtE),
      providing the potential to identify QTLs with pleiotropy or specificity for RM-
      and NUE-related traits. A total of 129 QTLs (including 23 stable QTLs, which were
      repeatedly detected at least two environments or different N levels) were
      identified and 83 of them were integrated into 22 pleiotropic QTL clusters. Five
      RM-NUE, ten RM-specific and three NUE-specific QTL clusters with same directions
      of additive-effect implied two NUE-improving approaches (RM-based and N
      utilization-based directly) and provided valuable genomic regions for NUE
      improvement in rapeseed. Importantly, all of four major QTLs and most of stable
      QTLs (20 out of 23) detected here were related to RM traits under HN and/or LN
      levels, suggested that regulating RM to improve NUE would be more feasible than
      regulating N efficiency directly. These results provided the promising genomic
      regions for marker-assisted selection on RM-based NUE improvement in rapeseed.

PMID- 29033970
TI  - Spermine Regulates Pollen Tube Growth by Modulating Ca2+-Dependent Actin
      Organization and Cell Wall Structure.
AB  - Proper growth of the pollen tube depends on an elaborate mechanism that
      integrates several molecular and cytological sub-processes and ensures a cell
      shape adapted to the transport of gametes. This growth mechanism is controlled by
      several molecules among which cytoplasmic and apoplastic polyamines. Spermine
      (Spm) has been correlated with various physiological processes in pollen,
      including structuring of the cell wall and modulation of protein (mainly
      cytoskeletal) assembly. In this work, the effects of Spm on the growth of pear
      pollen tubes were analyzed. When exogenous Spm (100 MUM) was supplied to
      germinating pollen, it temporarily blocked tube growth, followed by the induction
      of apical swelling. This reshaping of the pollen tube was maintained also after
      growth recovery, leading to a 30-40% increase of tube diameter. Apical swelling
      was also accompanied by a transient increase in cytosolic calcium concentration
      and alteration of pH values, which were the likely cause for major reorganization
      of actin filaments and cytoplasmic organelle movement. Morphological alterations
      of the apical and subapical region also involved changes in the deposition of
      pectin, cellulose, and callose in the cell wall. Thus, results point to the
      involvement of Spm in cell wall construction as well as cytoskeleton organization
      during pear pollen tube growth.

PMID- 29033968
TI  - Dancing with Hormones: A Current Perspective of Nitrate Signaling and Regulation
      in Arabidopsis.
AB  - In nature and agriculture, nitrate availability is a main environmental cue for
      plant growth, development and stress responses. Nitrate signaling and regulation
      are hence at the center of communications between plant intrinsic programs and
      the environment. It is also well known that endogenous phytohormones play
      numerous critical roles in integrating extrinsic cues and intrinsic responses,
      regulating and refining almost all aspects of plant growth, development and
      stress responses. Therefore, interaction between nitrate and phytohormones, such
      as auxins, cytokinins, abscisic acid, gibberellins, and ethylene, is prevalent.
      The growing evidence indicates that biosynthesis, de-conjugation, transport, and
      signaling of hormones are partly controlled by nitrate signaling. Recent advances
      with nitrate signaling and transcriptional regulation in Arabidopsis give rise to
      new paradigms. Given the comprehensive nitrate transport, sensing, signaling and
      regulations at the level of the cell and organism, nitrate itself is a local and
      long-distance signal molecule, conveying N status at the whole-plant level. A
      direct molecular link between nitrate signaling and cell cycle progression was
      revealed with TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR1-20 (TCP20) 
      NIN-LIKE PROTEIN 6/7 (NLP6/7) regulatory nexus. NLPs are key regulators of
      nitrogen responses in plants. TCPs function as the main regulators of plant
      morphology and architecture, with the emerging role as integrators of plant
      developmental responses to the environment. By analogy with auxin being proposed
      as a plant morphogen, nitrate may be an environmental morphogen. The morphogen
      gradient-dependent and cell-autonomous mechanisms of nitrate signaling and
      regulation are an integral part of cell growth and cell identification. This is
      especially true in root meristem growth that is regulated by intertwined nitrate,
      phytohormones, and glucose-TOR signaling pathways. Furthermore, the nitrate
      transcriptional hierarchy is emerging. Nitrate regulators in primary nitrate
      signaling can individually and combinatorially control downstream transcriptional
      networks and hormonal pathways for signal propagation and amplification. Under
      the new paradigms, nitrate-induced hormone metabolism and signaling deserve fresh
      examination. The close interplay and convergent regulation of nitrate and
      hormonal signaling at morphological, physiological, and molecular levels have
      significant effects on important agronomic traits, especially nutrient-dependent
      adaptive root system growth and architecture.

PMID- 29033973
TI  - Comparison of Central, Ambulatory, Home and Office Blood Pressure Measurement as
      Risk Markers for Mild Cognitive Impairment in Hypertensive Patients.
AB  - AIMS: We compared the role of central blood pressure (BP), ambulatory BP
      monitoring (ABPM), home-measured BP (HMBP) and office BP measurement as risk
      markers for the development of mild cognitive impairment (MCI). METHODS: 70
      hypertensive patients on combination medical therapy were studied. Their mean age
      was 64.97 +/- 8.88 years. Eighteen (25.71%) were males and 52 (74.28%) females.
      All of the patients underwent full physical examination, laboratory screening,
      echocardiography, and office, ambulatory, home and central BP measurement. The
      neuropsychological tests used were: Mini Mental State Examination (MMSE) and
      Montreal Cognitive Assessment (MoCA). SPSS 19 was used for the statistical
      analysis with a level of significance of 0.05. RESULTS: The mean central pulse
      pressure values of patients with MCI were significantly (p = 0.016) higher than
      those of the patients without MCI. There was a weak negative correlation between
      central pulse pressure and the results from the MoCA and MMSE (r = -0.283, p =
      0.017 and r = -0.241, p = 0.044, respectively). There was a correlation between
      ABPM and MCI as well as between HMBP and MCI. CONCLUSIONS: The correlation of
      central BP with target organ damage (MCI) is as good as for the other types of
      measurements of BP (home and ambulatory). Office BP seems to be the poorest
      marker for the assessment of target organ damage.

PMID- 29033972
TI  - Clinical Spectrum, Risk Factors, and Behavioral Abnormalities among Dementia
      Subtypes in a North Indian Population: A Hospital-Based Study.
AB  - BACKGROUND: As variability in the clinical profile of dementia subtypes had been
      reported with regional differences across the world, we conducted a retrospective
      hospital-based study in a North Indian population. METHODS: We retrieved patient
      records from 2007 to 2014 for details of clinical evaluation, diagnosis,
      neuroimaging, biochemical investigations, and follow-up of 1,876 patients with
      dementia (PwD), and the data were analyzed using descriptive statistics. RESULTS:
      Of the total PwD, Alzheimer disease (AD) accounted for 30% followed by vascular
      dementia (VaD) 26%, mixed dementia (MD) 21%, Parkinson-related dementia 11%,
      frontotemporal dementia (FTD) 7%, and infective dementia 5%. Of all PwD excluding
      the infective group (n = 1,777), 63% were men, 39% were from rural areas, 87% had
      behavioral abnormalities along with cognitive deficits, and 73% had impaired
      ADLs. Among dementia subtypes, a positive family history, cardiovascular and
      metabolic risk factors, and behavioral abnormalities were found to be
      distributed. However, there existed a predominance of specific behavioral pattern
      in each subtype. The mean duration of follow-up varied from 2.9 +/- 2.3 (VaD) to
      3.6 +/- 2.1 (AD) and greater than 30% were found to be stable on treatment
      (except in dementia with Lewy body). CONCLUSIONS: This large hospital-based study
      provides a distribution pattern and clinical spectrum of dementia subtypes in a
      North Indian population.

PMID- 29033974
TI  - Cognitive Deficits in Chronic Stroke Patients: Neuropsychological Assessment,
      Depression, and Self-Reports.
AB  - BACKGROUND: Following stroke, clinicians are challenged to detect and untangle
      symptoms of cognitive dysfunction and mood disorders. Additionally, they need to
      evaluate the informative value of self-reports to identify patients in need of
      further attendance. AIMS: To examine the association between neuropsychological
      measures, symptoms of depression, and self-reported cognitive function. METHODS:
      One-hundred and five chronic stroke patients underwent assessment covering 6
      cognitive domains and answered the Hospital Anxiety and Depression Scale and the
      Memory and Thinking Scale from the Stroke Impact Scale 1 year after stroke. Age
      and gender difference in cognitive impairment were examined; linear regression
      was used to predict depression scores. Sensitivity and specificity analyses were
      used to validate self-reported functioning against performance on cognitive
      tests. RESULTS: Cognitive impairment was observed in 60% of the patients in at
      least 1 cognitive domain. Cognitive performance was associated with symptoms of
      depression as well as with self-reported cognitive function. The final analyses
      revealed low sensitivity and specificity for the Memory and Thinking subscale
      from the Stroke Impact Scale. CONCLUSION: Cognitive impairment occurs frequently
      even in patients in a chronic phase after stroke and predicts symptoms of
      depression. Using the Stroke Impact Scale, clinicians should be aware of low
      sensitivity of self-reported cognitive function.

PMID- 29033975
TI  - A Hypothesis and Review of the Relationship between Selection for Improved
      Production Efficiency, Coping Behavior, and Domestication.
AB  - Coping styles in response to stressors have been described both in humans and in
      other animal species. Because coping styles are directly related to individual
      fitness they are part of the life history strategy. Behavioral styles trade off
      with other life-history traits through the acquisition and allocation of
      resources. Domestication and subsequent artificial selection for production
      traits specifically focused on selection of individuals with energy sparing
      mechanisms for non-production traits. Domestication resulted in animals with low
      levels of aggression and activity, and a low hypothalamic-pituitary-adrenal (HPA)
      axis reactivity. In the present work, we propose that, vice versa, selection for
      improved production efficiency may to some extent continue to favor docile
      domesticated phenotypes. It is hypothesized that both domestication and selection
      for improved production efficiency may result in the selection of reactive style
      animals. Both domesticated and reactive style animals are characterized by low
      levels of aggression and activity, and increased serotonin neurotransmitter
      levels. However, whereas domestication quite consistently results in a decrease
      in the functional state of the HPA axis, the reactive coping style is often found
      to be dominated by a high HPA response. This may suggest that fearfulness and
      coping behavior are two independent underlying dimensions to the coping response.
      Although it is generally proposed that animal welfare improves with selection for
      calmer animals that are less fearful and reactive to novelty, animals bred to be
      less sensitive with fewer desires may be undesirable from an ethical point of
      view.

PMID- 29033976
TI  - confFuse: High-Confidence Fusion Gene Detection across Tumor Entities.
AB  - Background: Fusion genes play an important role in the tumorigenesis of many
      cancers. Next-generation sequencing (NGS) technologies have been successfully
      applied in fusion gene detection for the last several years, and a number of NGS
      based tools have been developed for identifying fusion genes during this period.
      Most fusion gene detection tools based on RNA-seq data report a large number of
      candidates (mostly false positives), making it hard to prioritize candidates for
      experimental validation and further analysis. Selection of reliable fusion genes
      for downstream analysis becomes very important in cancer research. We therefore
      developed confFuse, a scoring algorithm to reliably select high-confidence fusion
      genes which are likely to be biologically relevant. Results: confFuse takes
      multiple parameters into account in order to assign each fusion candidate a
      confidence score, of which score >=8 indicates high-confidence fusion gene
      predictions. These parameters were manually curated based on our experience and
      on certain structural motifs of fusion genes. Compared with alternative tools,
      based on 96 published RNA-seq samples from different tumor entities, our method
      can significantly reduce the number of fusion candidates (301 high-confidence
      from 8,083 total predicted fusion genes) and keep high detection accuracy
      (recovery rate 85.7%). Validation of 18 novel, high-confidence fusions detected
      in three breast tumor samples resulted in a 100% validation rate. Conclusions:
      confFuse is a novel downstream filtering method that allows selection of highly
      reliable fusion gene candidates for further downstream analysis and experimental
      validations. confFuse is available at https://github.com/Zhiqin-HUANG/confFuse.

PMID- 29033977
TI  - The Empirical Distribution of Singletons for Geographic Samples of DNA Sequences.
AB  - Rare variants are important for drawing inference about past demographic events
      in a species history. A singleton is a rare variant for which genetic variation
      is carried by a unique chromosome in a sample. How singletons are distributed
      across geographic space provides a local measure of genetic diversity that can be
      measured at the individual level. Here, we define the empirical distribution of
      singletons in a sample of chromosomes as the proportion of the total number of
      singletons that each chromosome carries, and we present a theoretical background
      for studying this distribution. Next, we use computer simulations to evaluate the
      potential for the empirical distribution of singletons to provide a description
      of genetic diversity across geographic space. In a Bayesian framework, we show
      that the empirical distribution of singletons leads to accurate estimates of the
      geographic origin of range expansions. We apply the Bayesian approach to
      estimating the origin of the cultivated plant species Pennisetum glaucum [L.] R.
      Br. (pearl millet) in Africa, and find support for range expansion having started
      from Northern Mali. Overall, we report that the empirical distribution of
      singletons is a useful measure to analyze results of sequencing projects based on
      large scale sampling of individuals across geographic space.

PMID- 29033978
TI  - Integrative Analysis of Transcription Factor Combinatorial Interactions Using a
      Bayesian Tensor Factorization Approach.
AB  - Transcription factors play a key role in transcriptional regulation of genes and
      determination of cellular identity through combinatorial interactions. However,
      current studies about combinatorial regulation is deficient due to lack of
      experimental data in the same cellular environment and extensive existence of
      data noise. Here, we adopt a Bayesian CANDECOMP/PARAFAC (CP) factorization
      approach (BCPF) to integrate multiple datasets in a network paradigm for
      determining precise TF interaction landscapes. In our first application, we apply
      BCPF to integrate three networks built based on diverse datasets of multiple cell
      lines from ENCODE respectively to predict a global and precise TF interaction
      network. This network gives 38 novel TF interactions with distinct biological
      functions. In our second application, we apply BCPF to seven types of cell type
      TF regulatory networks and predict seven cell lineage TF interaction networks,
      respectively. By further exploring the dynamics and modularity of them, we find
      cell lineage-specific hub TFs participate in cell type or lineage-specific
      regulation by interacting with non-specific TFs. Furthermore, we illustrate the
      biological function of hub TFs by taking those of cancer lineage and blood
      lineage as examples. Taken together, our integrative analysis can reveal more
      precise and extensive description about human TF combinatorial interactions.

PMID- 29033979
TI  - Participation in cooperative prey capture and the benefits gained from it are
      associated with individual personality.
AB  - In animal societies, behavioral idiosyncrasies of the individuals often guide
      which tasks they should perform. Such personality-specific task participation can
      increase individual task efficiency, thereby improving group performance. While
      several recent studies have documented group-level benefits of within-group
      behavioral (i.e., personality) diversity, how these benefits are realized at the
      individual level is unclear. Here we probe the individual-level benefits of
      personality-driven task participation in the social spider Stegodyphus dumicola.
      In S. dumicola, the presence of at least one highly bold individual catalyzes
      foraging behavior in shy colony members, and all group constituents heavily
      compete for prey. We assessed boldness by examining how quickly spiders resumed
      normal movement after a simulated predator attack. We test here whether (1)
      participants in collective foraging gain more mass from prey items and (2)
      whether bold individuals are less resistant to starvation than shy spiders, which
      would motivate the bold individuals to forage more. Next, we assembled colonies
      of shy spiders with and without a bold individual, added one prey item, and then
      tracked the mass gain of each individual spider after this single feeding event.
      We found that spiders that participated in prey capture (whether bold or shy)
      gained more mass than nonparticipators, and colonies containing a single bold
      spider gained more total mass than purely shy colonies. We also found that bold
      spiders participated in more collective foraging events and were more susceptible
      to starvation than shy spiders, suggesting that the aggressive foraging of bold
      individuals may represent a strategy to offset starvation risk. These findings
      add to the body of evidence that animal personality can shape social
      organization, individual performance, and group success.

PMID- 29033981
TI  - Spatial Variation of Ground Level Ozone Concentrations and its Health Impacts in
      an Urban Area in India.
AB  - The present study was designed to analyze the spatial distributions of ground
      level ozone (GLO) concentrations in Ranchi (Jharkhand, India) using
      geostatistical approaches. From September 2014 to August 2015, monthly GLO
      concentrations were monitored in 40-identified locations distributed in the
      region of study. In every month, the monitoring was done at three different time
      periods of the day; 5.30 AM to 7.30 AM, 11.30 AM to 1.30 PM, and 5.30 PM to 8
      PM). The time duration was assigned based on the temporal variations of GLO
      concentrations. The descriptive statistics indicate that the spatial mean ozone
      concentrations ranged from 23.45 MUg m-3 to 53.91 MUg m-3 in morning hours, from
      82.50 MUg m-3 to 126.66 MUg m-3 in the day time and from 40.04 MUg m-3 to 71.25
      MUg m-3 in the evening hours. The higher level of spatial variance observed in
      the months of December (standard deviation: 24.21), July (standard deviation:
      29.59) and November (standard deviation: 19.60) for the morning, noon, and
      evening time, respectively. The effects of meteorological factors (wind speed and
      wind direction) on the ozone concentrations were also analysed. The study
      confirmed that wind speed is not the dominant factor for influencing the GLO
      concentrations. The study also analysed the ozone air quality index (OZAQI) for
      assessing the health impacts in the study area. The result suggests that most of
      the area had the moderate category of OZAQI (101-200) and that leads to breathing
      discomfort for people with lung and heart disease.

PMID- 29033980
TI  - Cellular, physiological and pathological aspects of the long non-coding RNA
      NEAT1.
AB  - BACKGROUND: The majority of mammalian genomes have been found to be transcribed
      into non-coding RNAs. One category of non-coding RNAs is classified as long non
      coding RNAs (lncRNAs) based on their transcript sizes larger than 200
      nucleotides. Growing evidence has shown that lncRNAs are not junk transcripts and
      play regulatory roles in multiple aspects of biological processes. Dysregulation
      of lncRNA expression has also been linked to diseases, in particular cancer.
      Therefore, studies of lncRNAs have attracted significant interest in the field of
      medical research. Nuclear enriched abundant transcript 1 (NEAT1), a nuclear
      lncRNA, has recently emerged as a key regulator involved in various cellular
      processes, physiological responses, developmental processes, and disease
      development and progression. OBJECTIVE: This review will summarize and discuss
      the most recent findings with regard to the roles of NEAT1 in the function of the
      nuclear paraspeckle, cellular pathways, and physiological responses and
      processes. Particularly, the most recently reported studies regarding the
      pathological roles of deregulated NEAT1 in cancer are highlighted in this review.
      METHODS: We performed a systematic literature search using the Pubmed search
      engine. Studies published over the last 8 years (between January 2009 and August
      2016) were the sources of literature review. The following keywords were used:
      "Nuclear enriched abundant transcript 1", "NEAT1", and "paraspeckles". RESULTS:
      The Pubmed search identified 34 articles related to the topic of the review.
      Among the identified literature, thirteen articles report findings related to
      cellular functions of NEAT1 and eight articles are the investigations of
      physiological functions of NEAT1. The remaining thirteen articles are studies of
      the roles of NEAT1 in cancers. CONCLUSION: Recent advances in NEAT1 studies
      reveal the multifunctional roles of NEAT1 in various biological processes, which
      are beyond its role in nuclear paraspeckles. Recent studies also indicate that
      dysregulation of NEAT1 function contributes to the development and progression of
      various cancers. More investigations will be needed to address the detailed
      mechanisms regarding how NEAT1 executes its cellular and physiological functions
      and how NEAT1 dysregulation results in tumorigenesis, and to explore the
      potential of NEAT1 as a target in cancer diagnosis, prognosis and therapy.

PMID- 29033982
TI  - Effects of multiwalled carbon nanotube surface modification and purification on
      bovine serum albumin binding and biological responses.
AB  - The potential diagnostic and therapeutic applications such as drug delivery of
      multi-walled carbon nanotubes (MWCNTs) are being increasingly explored due to
      their unique mechanical, chemical and biological properties. Carboxylation of
      MWCNTs has been widely used to improve the solubility in aqueous systems, and for
      further functionalization with biologically active moieties. Purity of
      carboxylated MWCNTs is of great importance in nanomedicine. An important
      consideration is that oxidation debris is generated during the process of
      carboxylation, which can be removed by base washing. We hypothesized that surface
      modification as well as further purification by debris removal may alter
      physicochemical properties of MWCNTs and their ability to bind proteins. In this
      study, we utilized pristine MWCNT carboxylated MWCNTs (F-MWCNTs) and base-washed
      carboxylated MWCNTs (BW-F-MWCNTs) to examine formation of a bovine serum albumin
      (BSA) protein corona and impact on biological responses. We found that
      carboxylation increased the capability of F-MWCNTs to bind BSA, and base washing
      further increased this binding by 41% implying that purification of F-MWCNTs is
      an important consideration in biological applications. The BSA protein corona
      decreased the hydrodynamic size of MWCNTs by nearly 50% because the coating
      improved colloidal behavior. The effect was significantly less pronounced for F
      MWCNTs and BW-F-MWCNTs because they were highly dispersible to begin with.
      Functionalization increased cellular uptake by both rat aortic endothelial cells
      (RAEC) and macrophage-like murine cells (RAW264.7), while base washing showed
      results similar to the functionalized analog. Interestingly, BSA binding
      downregulated mRNA levels of interleukin-6 (IL-6) and heme oxygenase 1 (Hmox1) in
      RAEC cells but upregulated the expression of IL-6 and Hmox1 in RAW264.7 cells,
      indicating the dependence of cell types in biological responses to MWCNTs.
      Overall, our study demonstrated that surface modification as well as further
      purification impacted the interaction of MWCNTs with proteins and subsequent
      cellular responses. Interestingly, while the corona associated with the F-MWCNTs
      and BW-F-MWCNTs were significantly different, their respective cellular uptake
      and biological responses were similar. This implied that surface
      functionalization played a more important role than surface corona.

PMID- 29033983
TI  - Sensor-Based Technique for Manually Scanned Hand-Held Optical Coherence
      Tomography Imaging.
AB  - Hand-held optical coherence tomography (OCT) imaging probes offer flexibility to
      image sites that are otherwise challenging to access. While the majority of hand
      held imaging probes utilize galvanometer- or MEMS-scanning mirrors to
      transversely scan the imaging beam, these probes are commonly limited to lateral
      fields-of-view (FOV) of only a few millimeters. The use of a freehand manually
      scanned probe can significantly increase the lateral FOV. However, using the
      traditional fixed-rate triggering scheme for data acquisition in a manually
      scanned probe results in imaging artifacts due to variations in the scan velocity
      of the imaging probe. These artifacts result in a structurally inaccurate image
      of the sample. In this paper, we present a sensor-based manual scanning technique
      for OCT imaging, where real-time feedback from an optical motion sensor is used
      to trigger data acquisition. This technique is able to circumvent the problem of
      motion artifacts during manual scanning by adaptively altering the trigger rate
      based on the instantaneous scan velocity, enabling OCT imaging over a large
      lateral FOV. The feasibility of the proposed technique is demonstrated by imaging
      several biological and nonbiological samples.

PMID- 29033984
TI  - Are food allergic consumers ready for informative precautionary allergen
      labelling?
AB  - Precautionary allergen labelling (PAL) has resulted in consumer confusion.
      Previous research has shown that interpretive labels (using graphics, symbols, or
      colours) are better understood than the traditional forms of labels. In this
      study, we aimed to understand if consumers would use interpretive labels (symbol,
      mobile phone application and a toll-free number) with or without medical advice
      that was advocated by the food industry rather than the normal PAL. This is
      relevant information for industry and clinicians as it provides an insight into
      the food allergic perception regarding PAL.

PMID- 29033985
TI  - The Effects of Acupressure on Pain Severity in Female Nurses with Chronic Low
      Back Pain.
AB  - BACKGROUND: Low back pain causes physical and psychological impacts among nurses.
      This study aimed to investigate the effects of acupressure on the severity of
      pain in chronic low back pain in female nurses. MATERIALS AND METHODS: This study
      is a single-blinded randomized clinical trial conducted among 50 nurses suffering
      from chronic low back pain. After simple sampling, participants were randomly
      assigned into acupressure and sham groups using lottery method (25 patients in
      each group). In the experimental group, the intervention was performed by the
      researcher three times a week throughout a 3-week period. The sham group received
      placebo interventions. Data was collected through VAS questionnaire before,
      immediately after, 2 weeks, and 4 weeks after performing intervention. Data
      analysis was conducted using SPSS version 18 using descriptive and inferential
      statistical methods. RESULTS: There was no significant difference in the mean
      pain severity scores in the pre-interventions phase between the groups (P =
      0.63), however, a significant difference was observed Immediately, 2 weeks, and 4
      weeks after performing intervention. Further, the mean pain severity scores in
      intervention group significantly decreased compared to the sham group (P =
      0.000). CONCLUSIONS: Acupressure on specific points was proved to reduce pain.
      Thus, acupressure can be used as nonmedicament, inexpensive, and without side
      effects treatment in reducing pain.

PMID- 29033986
TI  - Women Coping Strategies towards Menopause and its Relationship with Sexual
      Dysfunction.
AB  - BACKGROUND: Paying attention to sexual dysfunction and its coping strategies is
      essential owing to its impact on mental health in postmenopausal women and their
      families. This study aimed to determine the relationship between women coping
      strategies toward the process of menopause and sexual dysfunction in menopausal
      women. MATERIALS AND METHODS: This is a cross-sectional study in which 233
      married menopausal women were sampled in the first 5 years after cessation of
      menstrual cycle using health records in the health centers in Isfahan in 2015.
      The method of data collection was a demographic characteristics form, sexual
      function questionnaire of Rosen et al., along with a researcher-made coping
      strategies questionnaire. The validity and reliability of these instruments were
      assessed, and the resulting data were analyzed utilizing inferential statistical
      tests (t-test and Chi-square test) and SPSS 16 software. RESULTS: According to
      the results of this study, the relative frequency of sexual dysfunction in
      menopausal women is 67.42%. The mean score of the avoidance strategy in people
      with overall sexual dysfunction was significantly higher than the group without
      disorder (P < 0.001). The mean of coping strategies of social support seeking (P
      < 0.001), problem-solving (P = 0.016), and target replacement strategy (P =
      0.004) were significantly lower than that in the group without disorder.
      CONCLUSIONS: In line with the findings of this study, problem-oriented strategies
      such as social support, problem solving, and target replacement are the best
      strategies for decreasing sexual dysfunction or increasing sexual satisfaction.
      These results emphasize the reinforcement of health personnel skills in teaching
      approach of these strategies to this group of women.

PMID- 29033987
TI  - Dietary Practices and Nutritional Profile of Female Nurses from Government
      Hospitals in Delhi, India.
AB  - BACKGROUND: Nursing is a demanding profession and nurses face a considerable
      degree of stress at work that can adversely influence their dietary practices and
      nutritional status. The current study was designed to conduct a preliminary
      investigation of the dietary practices and nutritional profile of nurses from
      government hospitals in Delhi. MATERIALS AND METHODS: A cross-sectional
      descriptive study was carried out among 80 female nurses aged between 25 and 39
      years from government hospitals. Data on demographic profile and dietary
      practices were gathered using a questionnaire-cum-interview schedule. Nutrient
      intake of the participants was determined using a 2-day 24-hour diet recall
      method, and adequacy of intake of nutrients was assessed using the Nutrient
      Adequacy Ratio approach. Weight, height, and waist circumference were recorded
      and the body mass index (BMI) and waist-to-height ratio (WHtR) were computed.
      RESULTS: Findings revealed that though majority of nurses were involved in
      rotating shift duties in their hospitals, more than two-thirds of them had more
      or less appropriate dietary practices. Intake of most nutrients, except iron,
      vitamin A, vitamin B12, dietary folate, and riboflavin ranged from fairly
      adequate to adequate among nearly 85% of the nurses. Approximately 70% of the
      nurses were categorized as overweight and obese and had a WHtR above 0.52.
      CONCLUSIONS: The study indicated that most female nurses in government hospitals
      in Delhi had appropriate dietary practices and nutrient intakes but still had
      high BMI and WHtR, which increased their vulnerability to health problems.

PMID- 29033988
TI  - Comparing the Effect of Auriculotherapy and Vitamin B6 on the Symptoms of
      Premenstrual Syndrome among the Students who Lived in the Dorm of Isfahan
      University of Medical Sciences.
AB  - BACKGROUND: Premenstrual syndrome (PMS) is a series of physical and psychological
      symptoms before menstruation which its prevalence around the world has been
      reported to be 80%. Consumption of vitamin B6 is a common treatment for this
      syndrome, and this study was conducted to compare the effect of auriculotherapy
      and vitamin B6 on the symptoms of premenstrual syndrome. MATERIALS AND METHODS:
      This study was a clinical trial. Eighty-four female students who lived at the
      university dorm were randomly selected and allocated into two groups of 42. The
      first group received auriculotherapy (10 sessions) for two menstrual cycles and
      the second group consumed 40 mg of vitamin B6 daily from a week before their
      menstruation for two menstrual cycles. The severity of symptoms was recorded for
      both groups during two cycles before the intervention and two cycles after the
      intervention. Data gathering tool was a 28-question, questionnaire to assess the
      severity of symptoms of premenstrual syndrome based on DSM-IV. RESULTS: The mean
      score of symptoms in the auriculotherapy group in the first and second cycles was
      26.70 (19.49) and 24.76 (17.07), respectively, and in the vitamin B6 group, was
      22.60 (10.87) and 24.17 (14.15), respectively, which showed a significant
      difference compared to before the intervention (P = 0.001). However, comparing
      the total score of symptoms in the first and second cycles after the intervention
      between both groups showed no significant difference. CONCLUSIONS:
      Auriculotherapy, similar to vitamin B6, decreases the severity of PMS symptoms.

PMID- 29033989
TI  - Effectiveness of Back Massage on Sleep Pattern among Patients with Congestive
      Cardiac Failure.
AB  - BACKGROUND: Sleep plays an important role in congestive cardiac failure (CCF).
      Back massage reduces anxiety, discomfort, and physical suffering in CCF patients.
      Study objective is to assess sleep pattern in CCF patients before and after back
      massage. MATERIALS AND METHODS: A quasi-experimental study was conducted in
      Pravara Rural hospital, Loni, India over 4 months in 2016. Thirty CCF patients
      were included in the study with purposive sampling. Nurse investigator performed
      20-min back massage thrice daily, 5 min for each step from the day of admission
      till discharge. In back massage, effleurage, stroking, kneading, and assessment
      of effectiveness was recorded using the Pittsburg sleep quality index. RESULTS:
      Thirty CCF patients were included, out of which individuals aged >65, 56-65, and
      35-45 years age group were 40%, 24%, and 13%, respectively. Twenty-four had left
      and 6 had right heart failure. Distribution of mean and standard deviation of
      pretest for sleep quality was 9.50 (3.14), indicating poor sleep quality.
      Posttest, the mean score was 4.47 (0.89), indicating good quality sleep. Eleven
      patients had >8 h of sleep, 15 patients had 6-8 h of sleep, whereas 4 patients
      had less than 6 h of sleep pretest. Posttest, 22 patients had >8 h and the
      remaining had 6-8 h of sleep. CONCLUSIONS: Back massage technique is safe and
      cost-effective in CCF patients, by which the quality and duration of sleep is
      improved. It can be a part of the standard treatment.

PMID- 29033990
TI  - Investigating the Relation between Women's Body Image and Unconsummated Marriage.
AB  - BACKGROUND: Unconsummated marriage is considered to be one of the complicated
      sexual issues that lead to multiple complications and problems for couples as
      well as the society. It is thought that this disorder is more common in
      traditional cultures and some religions such as Islam, Hinduism, and Judaism. The
      aim of this study was to determine the relation between women's body image and
      unconsummated marriage. MATERIALS AND METHODS: This was a case-control study
      which was conducted among 50 women who had an unconsummated marriage (case group)
      and 100 women who had a consummated marriage (control group) in Isfahan, Iran
      during 2015-2016. Data were collected using the Multidimensional Body-Self
      Relations Questionnaire (MBSRQ). The data were analyzed using descriptive and
      inferential statistical tests. RESULTS: The total score of body image and all its
      components had no significant difference between both the groups of the case and
      the control (P > 0.05). CONCLUSIONS: Considering that no relation was found
      between body image and unconsummated marriage and the religious culture of the
      Iranian society with conservative sexual norms, investigating unconsummated
      marriage with emphasis on cultural factors is recommended. Hence, such sexual
      disorders would be avoided and the number of affected people and challenges can
      be decreased.

PMID- 29033992
TI  - Patient Safety Culture in Intensive Care Units from the Perspective of Nurses: A
      Cross-Sectional Study.
AB  - BACKGROUND: One of the goals of nursing is providing safe care, prevention of
      injury, and health promotion of patients. Patient safety in intensive care units
      is threatened for various reasons. This study aimed to survey patient safety
      culture from the perspective of nurses in intensive care units. MATERIALS AND
      METHODS: This cross-sectional study was conducted in 2016. Sampling was done
      using the convenience method. The sample consisted of 367 nurses working in
      intensive care units of teaching hospitals affiliated to Isfahan University of
      Medical Sciences. Data collection was performed using a two-part questionnaire
      that included demographic and hospital survey on Patient Safety Culture (HSOPSC)
      questionnaire. Data analysis was done using descriptive statistics (mean and
      standard deviation). RESULTS: Among the 12 dimensions of safety culture, the
      nurses assigned the highest score to "team work within units" (97.3%) and
      "Organizational learning-continuous improvement" (84%). They assigned the least
      score to "handoffs and transitions"(21.1%), "non-punitive response to errors"
      (24.7%), "Staffing" (35.6%), "Communication openness" (47.5%), and "Teamwork
      across units" (49.4%). CONCLUSIONS: The patient safety culture dimensions have
      low levels that require adequate attention and essential measures of health care
      centers including facilitating teamwork, providing adequate staff, and developing
      a checklist of handoffs and transitions. Furthermore, to increase reporting error
      and to promote a patient safety culture in intensive care units, some strategies
      should be adopted including a system-based approach to deal with the error.

PMID- 29033991
TI  - Comparison of Nurses and Parents' Viewpoints Regarding the Needs of Parents of
      Premature Infants in Neonatal Intensive Care Units.
AB  - BACKGROUND: The birth of a premature infant and her/his hospitalization can cause
      the parents to experience a variety of needs. Understanding the needs of parents
      by nurses can lead to provision of high quality care to premature infants. This
      study aimed to compare the parents' and nurses' viewpoints regarding parents'
      needs in the neonatal intensive care units (NICU). MATERIALS AND METHODS: In this
      descriptive cross-sectional study, 63 nurses, 120 mothers, and 120 fathers, who
      met the inclusion criteria, participated. Nurses were selected through a census
      method and parents through a simple convenience sampling method. Data were
      gathered using a researcher-made questionnaire and were analyzed using
      descriptive-analytic statistical methods in the Statistical Package for the
      Social Sciences software version 16. RESULTS: From the viewpoint of mothers, the
      need for assurance with a mean score of 87.4 was the most important and the need
      for support with a mean score of 71.37 was the least important need. From the
      perspective of fathers, the need for assurance with a mean score of 78.5 was the
      most important and the need for support with a mean score of 51.20 was the least
      important need. From the viewpoint of the nurses, the need for assurance with a
      mean score of 77.6 was the most important and the need for support with a mean
      score of 59.77 was the least important need. The mean scores of the needs of
      mothers in all subscales were higher than that of the fathers' and nurses' (P <
      0.001). CONCLUSIONS: From the viewpoint of nurses, the scores of parents' needs
      were significantly less than that of the parents' for all subscales. It is
      suggested that appropriate education programs be provided for nurses regarding
      how they can understand parents' needs to provide high quality care.

PMID- 29033993
TI  - Information Processing in Nursing Information Systems: An Evaluation Study from a
      Developing Country.
AB  - BACKGROUND: In recent years, information technology has been introduced in the
      nursing departments of many hospitals to support their daily tasks. Nurses are
      the largest end user group in Hospital Information Systems (HISs). This study was
      designed to evaluate data processing in the Nursing Information Systems (NISs)
      utilized in many university hospitals in Iran. METHODS AND MATERIALS: This was a
      cross-sectional study. The population comprised all nurse managers and NIS users
      of the five training hospitals in Khorramabad city (N = 71). The nursing subset
      of HIS-Monitor questionnaire was used to collect the data. Data were analyzed by
      the descriptive-analytical method and the inductive content analysis. RESULTS:
      The results indicated that the nurses participating in the study did not take a
      desirable advantage of paper (2.02) and computerized (2.34) information
      processing tools to perform nursing tasks. Moreover, the less work experience
      nurses have, the further they utilize computer tools for processing patient
      discharge information. The "readability of patient information" and "repetitive
      and time-consuming documentation" were stated as the most important expectations
      and problems regarding the HIS by the participating nurses, respectively.
      CONCLUSIONS: The nurses participating in the present study used to utilize paper
      and computerized information processing tools together to perform nursing
      practices. Therefore, it is recommended that the nursing process redesign
      coincides with NIS implementation in the health care centers.

PMID- 29033994
TI  - Effect of Dates in Late Pregnancy on the Duration of Labor in Nulliparous Women.
AB  - BACKGROUND: Long-term delivery is an important significant issue which is
      associated with mortality and fetal and maternal disorders. Based on the previous
      studies, consumption of dates affects uterine contractions and duration of
      delivery processes. This study aimed to study the effect of date consumption in
      late pregnancy on the duration of delivery processes in nulliparous women in
      2013. MATERIALS AND METHODS: This randomized clinical trial was conducted among
      182 nulliparous women 18-35 years who presented to OmAlBanin Hospital in Mashhad
      in 2013. The comparison has been made between 91 pregnant women who consumed 70
      76 g dates daily from the 37th week of pregnancy and 91 pregnant women who did
      not consume dates. Data collection tool was a questionnaire and a checklist of
      daily dates' intake. Data were analyzed using the Statistical Package for the
      Social Sciences software and statistical tests - chi-square and Mann-Whitney
      test, and P value <0.05 was considered significant. RESULTS: The average length
      of active phase (P = 0.0001), length of second phase (P = 0.0001), and third
      phase (P = 0.004) in two groups had statistically significant difference. The
      average length of the second phase (P = 0.03) and the third phase (P = 0.02) in
      case of spontaneous start of delivery in the intervention group was significantly
      lower than the control group. Use of oxytocin to accelerate delivery had a
      significant difference between the two groups (P < 0.001). CONCLUSION: According
      to the results of this study, consuming dates in late pregnancy was effective in
      decreasing length of labor processes and reduced the need of oxytocin for labor
      acceleration. Thus, it is recommended to consume dates in women without
      contraindications.

PMID- 29033996
TI  - Effects of Implementing the Alexander Technique on Enjoying the Sense of
      Motherhood in the Postpartum Period.
AB  - BACKGROUND: The broad concept of maternal well-being includes psychological
      concepts, social aspects, and aspects of becoming a mother. The present study
      aimed to investigate the effects of implementing the Alexander technique on
      enjoying the sense of motherhood. MATERIALS AND METHODS: This study was a
      clinical trial conducted in two phases. In the first phase, using the exploratory
      and confirmatory factor analysis, 226 mothers were asked to undergo a scale test
      of enjoying the sense of motherhood after childbirth. In the second phase, 88
      pregnant women were divided into two experimental groups. The data collection
      tool was a researcher-made questionnaire about enjoying the sense of motherhood.
      Independent samples t-test, Mann-Whitney test, Chi-square test, Fisher's exact
      test, analysis of variance test, Box test, and Levine test were used to analyze
      the data. RESULTS: Results of this study showed that the mean scores of the
      constructs of enjoying pregnancy (P > 0.001), motherhood, and child care
      satisfaction (P > 0.001) in the experimental group were significantly higher than
      the control group. Moreover, the construct of trusting their own abilities to
      cope with maternal duties (P > 0.01) did not show significant differences between
      the two groups. CONCLUSIONS: The findings indicated that the Alexander technique
      can promote mothers' psychological well-being and their pleasure of becoming a
      mother and the related constructs. Results also revealed that using this
      technique, educating and recommending pregnant women to use this technique will
      be beneficial.

PMID- 29033995
TI  - Effect of Environmental and Behavioral Interventions on Pain Intensity in Preterm
      Infants for Heel Prick Blood Sampling in the Neonatal Intensive Care Unit.
AB  - BACKGROUND: Recent researches suggest that preterm infants understand pain and
      stress. Because of the wide range of effects of pain on infants, the present
      study was conducted on the effect of environmental and behavioral interventions
      on pain due to heel-prick blood sampling in preterm infants. MATERIALS AND
      METHODS: A clinical trial was conducted among 32 infants with gestational age of
      32-37 weeks in the intervention and control groups. The effects of noise
      reduction by earplugs, light reduction by blindfolds, reduction of nursing
      manipulation, and creation of intrauterine position for neonates, 30 minutes
      before taking blood samples until 30 minutes after it, were measured during the
      intervention stage. Data were collected using the Neonatal Infant Pain Scale
      (NIPS) in 5 stages (before intervention, 2 minutes before sampling, during the
      sampling, and 5 minutes and 30 minutes after the sampling). The data were
      analyzed using analysis of variance (ANOVA) and paired t-test in SPSS software.
      RESULTS: The paired t-test results showed no significant differences between the
      control and intervention stages in terms of pain scores at base time (P = 0.42)
      and 2 minutes before sampling (P = 0.12). However, at the sampling time (P =
      0.0), and 5 minutes (P = 0.001) and 30 minutes after the sampling (P = 0.001),
      mean pain score in the intervention stage was significantly less than that in the
      control stage. CONCLUSIONS: Based on the findings, environmental and behavioral
      interventions reduced pain and facilitated heel-prick blood sampling in preterm
      infants.

PMID- 29033997
TI  - The Effects of Cognitive-Behavioral Stress Management on Nurses' Job Stress.
AB  - BACKGROUND: Job stress is a prevalent and costly problem in different working
      conditions. Stress can degrade care quality in nurses and elevate their
      willingness to leave the job. This study aimed to determine the effects of
      cognitive-behavioral stress management on nurses' job stress. MATERIALS AND
      METHODS: In this quasi-experimental study with a control group, 40 nurses from
      the educational hospitals in Birjand who had completed a job stress questionnaire
      with a score of more than 100 were selected and randomly allocated to two groups.
      The intervention group underwent eight 2-hour sessions training of cognitive
      behavioral stress management (one session per week), whereas the control group
      had no such training. Two months after the training, the two groups completed the
      hospital job stress questionnaire again. The data were analyzed using Statistical
      Package for the Social Sciences (version 19) by Chi-square, Fisher exact test,
      independent t-test, and paired t-tests at 0.05 significance level. RESULTS:
      Stress mean score and standard deviation before and after the intervention were
      3.48 (0.22) and 2.8 (0.2) in the intervention group and 3.48 (0.21) and 3.56
      (0.2) in the control group, respectively. In the intervention group, the overall
      mean scores of stress and its dimensions significantly decreased after the
      intervention (P < 0.05). CONCLUSIONS: Given the significant decrease in the
      nurses' stress using cognitive-behavioral stress management, this approach can be
      suggested to be taught to nurses in hospitals in order to decrease their stress
      and increase their efficiency.

PMID- 29033998
TI  - Effect of Kangaroo Care Combined with Music on the Mother-premature Neonate
      Attachment: A Randomized Controlled Trial.
AB  - BACKGROUND: Premature birth may complicate the development and quality of the
      mother-infant attachment relationship. Music and kangaroo care are two common
      complementary cares performed in the neonatal intensive care unit (NICU). The
      present study investigated the effect of kangaroo care combined with music on the
      mother-premature neonate attachment. MATERIALS AND METHODS: In this clinical
      trial, 64 mothers with premature neonates were selected and assigned to the
      control and study groups through random allocation. In the control group,
      kangaroo care, and in the study group, kangaroo care combined with music was
      adopted. The level of mother-premature neonate attachment was measured and
      compared before and after the intervention in both the groups using Avant's
      Maternal Attachment Assessment Scale. RESULTS: There was a significant increase
      in the mean overall score of attachment in the kangaroo care combined with music
      group (70.72 (11.46)) after the intervention compared to the kangaroo care
      without music group (53.61 (9.76)). CONCLUSIONS: The mean overall score of mother
      neonate attachment in the kangaroo care combined with music group was higher than
      the kangaroo care group. This difference can be related to the effectiveness of
      music combined with kangaroo care.

PMID- 29033999
TI  - Reminding the Health Team About What Companions of the Patients Undergoing
      Gynecological Surgery Should Know: A Qualitative Study.
AB  - BACKGROUND: Patients' family members often do not receive sufficient information,
      especially because the reproductive system of women is considered a taboo,
      providing information becomes problematic. The aim of the current study was to
      explore the informational-educational needs of companions of the patients who
      were undergoing gynecological surgery. MATERIALS AND METHODS: This study was
      conducted using inductive and conventional content analysis method. For data
      collection, 34 semi-structured in-depth interviews were performed at a gynecology
      and obstetrics center with purposeful sampling and maximum variation. The
      participants included patients' companions, nurses, physicians, patients, and
      service personnel. RESULTS: Qualitative content analysis extracted 8 categories,
      2 main categories of "Informational needs of companions" and "Educational needs
      of companions" and a final theme of "the need for knowing." CONCLUSIONS:
      According to the results, "the need for knowing" is one of the most important
      needs of the patients' companions during hospitalization. Knowing companions'
      needs in the hospital and understanding its deficiencies would assist health care
      professionals, especially authorities, in providing high-quality care and
      developing programs to meet the informational needs of patients' companions.

PMID- 29034000
TI  - Ethnographic Exploration of Empowerment to Improve Elderly Residents' Quality of
      Life.
AB  - BACKGROUND: Evidence underscores that empowerment is central to improve the
      elderly residents' quality of life. In truth, empowerment is a process through
      which individuals gain better control over their life. The aim of this study was
      to explore how perceived empowerment influence on the quality of life among
      elderly Malay residents. MATERIALS AND METHODS: A focus ethnographic approach was
      employed in a Malaysian residential home between May 2011 and January 2012. Data
      were gathered from participant observations, field notes, in-depth interviews,
      and exploring related documents. RESULTS: The analysis of the data gathered in
      the current study resulted in the development of three themes - social life and
      its requirements, caregivers' skills empowerment, and listening and supporting.
      CONCLUSIONS: Findings of the study provide new insights that are useful in
      charting new guideline for care providers and policy makers to improve the
      elderly residents' quality of life.

PMID- 29034001
TI  - Correction to: mouse mammary tumour virus (MMTV) and human breast cancer with
      neuroendocrine differentiation.
AB  - [This corrects the article DOI: 10.1186/s13027-017-0135-8.].

PMID- 29034002
TI  - Lumbopelvic rhythm in the sagittal plane: A review of the effects of participants
      and task characteristics.
AB  - OBJECTIVES: Abnormalities of lumbopelvic coordination have been suggested to
      relate to risk of developing low back pain. The objective of this study is to
      review and summarize the findings of studies that have implemented and reported
      on lumbopelvic rhythm during trunk forward bending and backward return. METHODS:
      The PUBMED and CINAHL databases were searched for studies related to LPR using
      appropriate keywords. The references of each study from the database search were
      further investigated to identify any missed study. RESULTS: The findings includes
      results related to lumbopelvic rhythm, and how it varies due to participant
      characteristics such as age, gender, and presence of low back pain as well as due
      to variations in the experimental procedures such as pace of motion, presence of
      external load, and muscle fatigue. CONCLUSION: In general, the magnitude of
      lumbar contribution is smaller in people with low back pain, in the elderly and
      females, as well as with greater pace of motion, but is larger with greater
      external load or back muscle fatigue. The compiled data in this review are
      expected to serve as a foundation for implementation of this kinematic-based
      measure in the conduct of future research.

PMID- 29034003
TI  - Cellulase hyper-production by Trichoderma reesei mutant SEU-7 on lactose.
AB  - BACKGROUND: The induction of cellulase production by insoluble carbon source
      cellulose was a common and efficient strategy, but has some drawbacks, such as
      difficult fermentation operation, substantial cellulase loss, long fermentation
      time, and high energy-consumption, resulting in high cost of cellulase production
      in industry. These drawbacks can be overcome if soluble carbon sources are
      utilized as the inducers for cellulase production. However, until now the
      induction efficiency of most soluble carbon sources, especially lactose and
      glucose, is still inferior to cellulose despite extensive efforts have been made
      by either optimizing the fermentation process or constructing the recombinant
      strains. Therefore, strain improvement by metabolic engineering for high
      induction efficiency of soluble carbon sources is of great interest. RESULTS:
      Trichoderma reesei mutant SEU-7 was constructed from T. reesei RUT-C30 with the
      overexpression of endogenous gene beta-glucosidase (BGL1) by insertional
      mutagenesis via Agrobacterium tumefaciens-mediated transformation (AMT). Compared
      to RUT-C30, SEU-7 displays substantially enhanced activities of both cellulase
      and hemicellulase when grown on either lactose or cellulose. The induction
      efficiency with lactose was found to be higher than cellulose in strain SEU-7. To
      the best of our knowledge, we achieved the highest FPase activity in SEU-7 in
      both batch culture (13.0 IU/mL) and fed-batch culture (47.0 IU/mL) on lactose.
      Moreover, SEU-7 displayed unrivaled pNPGase activity on lactose in both batch
      culture (81.0 IU/mL) and fed-batch culture (144.0 IU/mL) as compared to the other
      reported T. reesei strains in the literature grown in batch or fed-batch
      experiments on cellulose or lactose. This superiority of SEU-7 over RUT-C30
      improves markedly the saccharification ability of SEU-7 on pretreated corn
      stover. The overexpression of gene BGL1 was found either at the mRNA or at the
      protein level in the mutant strains with increased cellulase production in
      comparison with RUT-C30, but only SEU-7 displayed much higher expression of gene
      BGL1 on lactose than on cellulose. Two copies of gene BGL1 were inserted into the
      chromosome of T. reesei SEU-7 between KI911141.1:347357 and KI911141.1:347979,
      replacing the original 623-bp fragment that is not within any genes' coding
      region. The qRT-PCR analysis revealed that the mRNA levels of both cellulase and
      hemicellulase were upregulated significantly in SEU-7, together with the MFS
      transporter CRT1 and the XYR1 nuclear importer KAP8. CONCLUSIONS: Recombinant T.
      reesei SEU-7 displays hyper-production of both cellulase and hemicellulase on
      lactose with the highest FPase activity and pNPGase activity for T. reesei,
      enabling highly efficient saccharification of pretreated biomass. For the first
      time, the induction efficiency for cellulase production by lactose in T. reesei
      was reported to be higher than that by cellulose. This outperformance of T.
      reesei SEU-7, which is strain-specific, is attributed to both the overexpression
      of gene BGL and the collateral mutation. Moreover, the increased transcription
      levels of cellulase genes, the related transcription factors, and the MFS
      transporter CRT1 contribute to the outstanding cellulase production of SEU-7. Our
      research advances strain improvement to enhance the induction efficiency of
      soluble carbon sources to produce cost-effective cellulase and hemicellulase in
      industry.

PMID- 29034004
TI  - Genetic engineering of the Calvin cycle toward enhanced photosynthetic CO2
      fixation in microalgae.
AB  - BACKGROUND: Photosynthetic microalgae are emerging as potential biomass feedstock
      for sustainable production of biofuels and value-added bioproducts. CO2
      biomitigation through these organisms is considered as an eco-friendly and
      promising alternative to the existing carbon sequestration methods. Nonetheless,
      the inherent relatively low photosynthetic capacity of microalgae has hampered
      the practical use of this strategy for CO2 biomitigation applications. RESULTS:
      Here, we demonstrate the feasibility of improving photosynthetic capacity by the
      genetic manipulation of the Calvin cycle in the typical green microalga Chlorella
      vulgaris. Firstly, we fused a plastid transit peptide to upstream of the enhanced
      green fluorescent protein (EGFP) and confirmed its expression in the chloroplast
      of C. vulgaris. Then we introduced the cyanobacterial fructose 1,6-bisphosphate
      aldolase, guided by the plastid transit peptide, into C. vulgaris chloroplast,
      leading to enhanced photosynthetic capacity (~ 1.2-fold) and cell growth.
      Molecular and physiochemical analyses suggested a possible role for aldolase
      overexpression in promoting the regeneration of ribulose 1,5-bisphosphate in the
      Calvin cycle and energy transfer in photosystems. CONCLUSIONS: Our work
      represents a proof-of-concept effort to enhance photosynthetic capacity by the
      engineering of the Calvin cycle in green microalgae. Our work also provides
      insights into targeted genetic engineering toward algal trait improvement for CO2
      biomitigation uses.

PMID- 29034005
TI  - In vitro and in vivo modeling of lipid bioaccessibility and digestion from almond
      muffins: The importance of the cell-wall barrier mechanism.
AB  - This study compares in vitro and in vivo models of lipid digestion from almond
      particles within a complex food matrix (muffins) investigating whether the cell
      wall barrier regulates the bioaccessibility of nutrients within this matrix.
      Muffins containing small (AF) or large (AP) particles of almond were digested in
      triplicate using an in vitro dynamic gastric model (DGM, 1 h) followed by a
      static duodenal digestion (8 h). AF muffins had 97.1 +/- 1.7% of their lipid
      digested, whereas AP muffins had 57.6 +/- 1.1% digested. In vivo digestion of
      these muffins by an ileostomy volunteer (0-10 h) gave similar results with 96.5%
      and 56.5% lipid digested, respectively. The AF muffins produced a higher
      postprandial triacylglycerol iAUC response (by 61%) than the AP muffins.
      Microstructural analysis showed that some lipid remained encapsulated within the
      plant tissue throughout digestion. The cell-wall barrier mechanism is the main
      factor in regulating lipid bioaccessibility from almond particles.

PMID- 29034006
TI  - Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: It is unknown whether canagliflozin, a selective sodium glucose co
      transporter 2 inhibitor, reduces epicardial adipose tissue (EAT) thickness, which
      is associated with insulin resistance and is a risk factor for coronary artery
      disease. METHODS AND RESULTS: We administered 100 mg of canagliflozin for 6
      months to 13 patients with type 2 diabetes mellitus. We evaluated glycemic
      control, visceral adipose tissue (VAT) area and subcutaneous adipose tissue (SAT)
      area, and skeletal muscle mass by using impedance methods, and EAT thickness by
      using echocardiography. Canagliflozin treatment for 6 months decreased hemoglobin
      A1c level from 7.1 +/- 0.5% to 6.7 +/- 0.6% (P < 0.05) and decreased EAT
      thickness from 9.3 +/- 2.5 to 7.3 +/- 2.0 mm (P < 0.001), along with a trend of
      decreasing VAT and SAT area. No association was found between any of these
      changes. CONCLUSION: Canagliflozin reduced EAT thickness in patients with type 2
      diabetes mellitus independent of its effect on lowering blood glucose, suggesting
      that canagliflozin may have an effect in preventing cardiovascular events in
      these patients (UMIN000021327).

PMID- 29034007
TI  - Microfluidic Iterative Mechanical Characteristics (iMECH) Analyzer for Single
      Cell Metastatic Identification.
AB  - This study describes the development of a microfluidic biosensor called the
      iterative mechanical characteristics (iMECH) analyzer which enables label-free
      biomechanical profiling of individual cells for distinction between metastatic
      and non-metastatic human mammary cell lines. Previous results have demonstrated
      that pulsed mechanical nanoindentation can modulate the biomechanics of cells
      resulting in distinctly different biomechanical responses in metastatic and non
      metastatic cell lines. The iMECH analyzer aims to move this concept into a
      microfluidic, clinically more relevant platform. The iMECH analyzer directs a
      cyclic deformation regimen by pulling cells through a test channel comprised of
      narrow deformation channels and interspersed with wider relaxation regions which
      together simulate a dynamic microenvironment. The results of the iMECH analysis
      of human breast cell lines revealed that cyclic deformations produce a resistance
      in non-metastatic 184A1 and MCF10A cells as determined by a drop in their average
      velocity in the iterative deformation channels after each relaxation. In
      contrast, metastatic MDA-MB-231 and MDA-MB-468 cells exhibit a loss of resistance
      as measured by a velocity raise after each relaxation. These distinctive
      modulatory mechanical responses of normal-like non-metastatic and metastatic
      cancer breast cells to the pulsed indentations paradigm provide a unique bio
      signature. The iMECH analyzer represents a diagnostic microchip advance for
      discriminating metastatic cancer at the single-cell level.

PMID- 29034008
TI  - Surface-ligand effect on radiosensitization of ultrasmall luminescent gold
      nanoparticles.
AB  - Gold nanoparticles (AuNPs) could serve as potential radiotherapy sensitizers
      because of their exceptional biocompatibility and high-Z material nature;
      however, since in vitro and in vivo behaviors of AuNPs are determined not only by
      their particle size but also by their surface chemistries, whether surface
      ligands can affect their radiosensitization has seldom been investigated in the
      radiosensitization of AuNPs. By conducting head-to-head comparison on
      radiosensitization of two kinds of ultrasmall (~2 nm) near-infrared (NIR)
      emitting AuNPs that are coated with zwitterionic glutathione and neutral
      polyethylene glycol (PEG) ligands, respectively, we found that zwitterionic
      glutathione coated AuNPs (GS-AuNPs) can reduce survival rates of MCF-7 cells
      under irradiation of clinically used megavoltage photon beam at low dosage of
      ~2.25 Gy. On the other hand, PEG-AuNPs can serve as a radiation-protecting agent
      and enabled MCF-7 cells more resistant to the irradiation, clearly indicating the
      key role of surface chemistry in radiosensitization of AuNPs. More detailed
      studies suggested that such difference was independent of cellular uptake and its
      efficiency, but might be related to the ligand-induced difference in
      photoelectron generation and/or interactions between AuNPs and X-ray triggered
      reactive oxygen species (ROS).

PMID- 29034010
TI  - Developing a framework of gastronomic systems research to unravel drivers of food
      choice.
AB  - Nutritional and dietary interventions and the introduction of novel food products
      and ingredients require a thorough understanding of the drivers of food choice,
      which are embedded in local context and culture. We developed a framework of
      "gastronomic systems research" (GSR) to understand culture-specific consumer food
      choice, and contextualise it to a target population of urban, middle- to high
      income Filipino consumers to assess the domestic niche market potential of
      traditional rice varieties in the Philippines. The GSR framework was
      contextualised through expert elicitation involving chefs and nutritionists, and
      validated through a consumer survey conducted during a food exposition. Using the
      GSR framework, we determined indicative rice consumption patterns of the target
      population and the specific rice quality attributes they require for specific
      rice-based dishes and rice consumption occasions. The GSR framework also reveals
      possible entry points for nutritional and dietary interventions and the
      introduction of novel food products and ingredients. The GSR framework,
      therefore, has the potential to aid policymakers and food value chain
      stakeholders in designing culture-sensitive and context-appropriate interventions
      not only to help consumers improve their diets, but also to help farmers access
      niche markets for novel food products and ingredients and thereby improve their
      livelihoods and preserve cultural heritage.

PMID- 29034011
TI  - The development of iconicity in children's co-speech gesture and homesign.
AB  - Gesture can illustrate objects and events in the world by iconically reproducing
      elements of those objects and events. Children do not begin to express ideas
      iconically, however, until after they have begun to use conventional forms. In
      this paper, we investigate how children's use of iconic resources in gesture
      relates to the developing structure of their communicative systems. Using
      longitudinal video corpora, we compare the emergence of manual iconicity in
      hearing children who are learning a spoken language (co-speech gesture) to the
      emergence of manual iconicity in a deaf child who is creating a manual system of
      communication (homesign). We focus on one particular element of iconic gesture -
      the shape of the hand (handshape). We ask how handshape is used as an iconic
      resource in 1-5-year-olds, and how it relates to the semantic content of
      children's communicative acts. We find that patterns of handshape development are
      broadly similar between co-speech gesture and homesign, suggesting that the
      building blocks underlying children's ability to iconically map manual forms to
      meaning are shared across different communicative systems: those where gesture is
      produced alongside speech, and those where gesture is the primary mode of
      communication.

PMID- 29034009
TI  - A multicenter, randomized study of decitabine as epigenetic priming with
      induction chemotherapy in children with AML.
AB  - BACKGROUND: Decitabine is a deoxycytidine nucleoside derivative inhibitor of DNA
      methyltransferases, which has been studied extensively and is approved for
      myelodysplastic syndrome in adults but with less focus in children. Accordingly,
      we conducted a phase 1 multicenter, randomized, open-label study to evaluate
      decitabine pre-treatment before standard induction therapy in children with newly
      diagnosed AML to assess safety and tolerability and explore a number of biologic
      endpoints. RESULTS: Twenty-four patients were fully assessable for all study
      objectives per protocol (10 in Arm A = epigenetic priming induction, 14 in Arm B
      = standard induction). All patients experienced neutropenia and thrombocytopenia.
      The most common grade 3 and 4 non-hematologic adverse events observed were
      gastrointestinal toxicities and hypophosphatemia. Plasma decitabine PK were
      similar to previously reported adult data. Overall CR/CRi was similar for the two
      arms. MRD negativity at end-induction was 85% in Arm A versus 67% in Arm B
      patients. DNA methylation measured in peripheral blood over the course of
      treatment tracked with blast clearance and matched marrow aspirates at day 0 and
      day 21. Unlike end-induction marrow analyses, promoter methylation in blood
      identified an apparent reversal of response in the lone treatment failure, 1 week
      prior to the patient's marrow aspirate confirming non-response. Decitabine
      induced effects on end-induction (day 35-43 following initiation of treatment)
      marrows in Arm A were reflected by changes in DNA methylation in matched paired
      marrow diagnostic aspirates. CONCLUSIONS: This first-in-pediatrics trial
      demonstrates that decitabine prior to standard combination chemotherapy is
      feasible and well tolerated in children with newly diagnosed AML. Pre-treatment
      with decitabine may represent a newer therapeutic option for pediatric AML,
      especially as it appears to induce important epigenetic alterations. The novel
      biological correlates studied in this trial offer a clinically relevant window
      into disease progression and remission. Additional studies are needed to
      definitively assess whether decitabine can enhance durability responses in
      children with AML. TRIAL REGISTRATION: NCT01177540.

PMID- 29034012
TI  - Auditory word recognition across the lifespan: Links between linguistic and
      nonlinguistic inhibitory control in bilinguals and monolinguals.
AB  - Recent research suggests that bilingual experience reconfigures linguistic and
      nonlinguistic cognitive processes. We examined the relationship between
      linguistic competition resolution and nonlinguistic cognitive control in younger
      and older adults who were either bilingual or monolingual. Participants heard
      words in English and identified the referent among four pictures while eye
      movements were recorded. Target pictures (e.g., cab) appeared with a phonological
      competitor picture (e.g., cat) and two filler pictures. After each eye-tracking
      trial, priming probes assessed residual activation and inhibition of target and
      competitor words. When accounting for processing speed, results revealed that age
      related changes in activation and inhibition are smaller in bilinguals than in
      monolinguals. Moreover, younger and older bilinguals, but not monolinguals,
      recruited similar inhibition mechanisms during word identification and during a
      nonlinguistic Stroop task. Results suggest that, during lexical access,
      bilinguals show more consistent competition resolution and recruitment of
      cognitive control across the lifespan than monolinguals.

PMID- 29034013
TI  - Cardiovascular Events in Hemodialysis Patients: Challenging against Vascular
      Calcification.
AB  - Particularly in patients with hemodialysis, cardiovascular mortality rate is
      extremely high. Polyvascular diseases develop at an early stage of chronic kidney
      disease (CKD). Pathophysiology includes insulin resistance and/or imbalance
      between nitric oxide (NO) and endothelin bioavailability as well as oxidative
      stress. The understanding in pathophysiology of vascular calcification and
      strategic treatment is a critical issue to achieve favorable outcome for the
      patients with CKD. In this article, we aim to review the cardiovascular disease
      for the patients with CKD with a particular emphasis on the clinical aspects of
      polyvascular disease. Finally, we address to detect microcirculatory impairment
      and eradicate vascular calcification as early as possible prior to renal
      replacement therapy. (This is a translation of Jpn J Vasc Surg 2016; 25: 359
      365.).

PMID- 29034015
TI  - A New Technique for Femoral Venous Access in Infants Using Arterial Injection
      Venous Return Guidance.
AB  - Objectives: Although venography guidance is helpful for central venous catheter
      placement, it is sometimes difficult to place a peripheral intravenous cannula
      for enhancement. We designed a new technique for establishing femoral venous
      access using venography guidance in the return phase of peripheral arteriography.
      This new technique was named arterial injection venous return guidance. Here we
      assessed the efficacy and safety of arterial injection venous return guidance.
      Methods: We reviewed data of 29 infants less than 6 months old undergoing
      catheter intervention at our institute in 2014. Of the 29 patients, femoral
      venous cannulation was performed using arterial injection venous return guidance
      in 5 patients, venography in 20 patients, and the landmark method in 4 patients.
      The technical success rates and incidence of complications were compared.
      Results: The overall success rates were 100% in the arterial injection venous
      return-guided and venography-guided groups. The mean procedure duration and mean
      contrast material injection time were similar between the groups. The contrast
      effect on the femoral vein in the arterial injection venous return-guided group
      was lower than that in the venography-guided group, but adequate for surgery. The
      overall complication rate was 17%, and obstruction of previously placed
      intravenous catheters was the most common complication. Conclusions: Therefore,
      the arterial injection venous return guidance technique was as safe and efficient
      as venography for establishing venous access.

PMID- 29034016
TI  - Improved Outcomes for Ruptured Abdominal Aortic Aneurysms Using Integrated
      Management Involving Endovascular Clamping, Endovascular Replacement, and Open
      Abdominal Decompression.
AB  - Objective: Endovascular repair has become the treatment of choice for ruptured
      abdominal aortic aneurysms (RAAAs). To improve surgical outcomes, preoperative
      management is important. In 2011, we introduced integrated management, which
      involves endovascular aneurysm repair, stabilization of hemodynamics by
      endovascular clamping, and open abdominal decompression to address abdominal
      compartment syndrome (ACS). Methods: To evaluate the efficacy of this management
      strategy, 62 patients who had undergone emergency surgery for an RAAA were
      analyzed retrospectively: group A (n=39), where an old strategy was used, and
      group B (n=23), where integrated management was introduced. Patient
      characteristics and 30-day mortality rates were compared between the two groups.
      Results: The average patient age was 67.7 years and 74.7 years for groups A and
      B, respectively (P=0.032). Group B patients required more frequent use of
      vasopressors (P=0.035). Other patient characteristics did not differ between the
      two groups. The duration of surgery was significantly shorter in group B than in
      group A (P=0.001). The total amount of transfused blood did not differ between
      the two groups. No patients showed symptoms of ACS. Early mortality rates were
      12.8% and 8.7% in groups A and B, respectively. The number of wound infections
      was significantly fewer in group B than in group A. Conclusion: Although group B
      patients were significantly older and had a higher rate of vasopressor use, early
      mortality was improved in both groups. Morbidity was significantly better in
      group B with respect to the duration of surgery and number of wound infections
      than in group A.

PMID- 29034014
TI  - Improving the Outcome of Vein Grafts: Should Vascular Surgeons Turn Veins into
      Arteries?
AB  - Autogenous vein grafts remain the gold standard conduit for arterial bypass,
      particularly for the treatment of critical limb ischemia. Vein graft adaptation
      to the arterial environment, i.e., adequate dilation and wall thickening,
      contributes to the superior performance of vein grafts. However, abnormal venous
      wall remodeling with excessive neointimal hyperplasia commonly causes vein graft
      failure. Since the PREVENT trials failed to improve vein graft outcomes, new
      strategies focus on the adaptive response of the venous endothelial cells to the
      post-surgical arterial environment. Eph-B4, the determinant of venous endothelium
      during embryonic development, remains expressed and functional in adult venous
      tissue. After surgery, vein grafts lose their venous identity, with loss of Eph
      B4 expression; however, arterial identity is not gained, consistent with loss of
      all vessel identity. In mouse vein grafts, stimulation of venous Eph-B4 signaling
      promotes retention of venous identity in endothelial cells and is associated with
      vein graft walls that are not thickened. Eph-B4 regulates downstream signaling
      pathways of relevance to vascular biology, including caveolin-1, Akt, and
      endothelial nitric oxide synthase (eNOS). Regulation of the Eph-B4 signaling
      pathway may be a novel therapeutic target to prevent vein graft failure.

PMID- 29034017
TI  - Surgical Management of Mycotic Aortic Aneurysms.
AB  - Purpose: A mycotic aneurysm is an uncommon disease associated with a high
      mortality rate when managed surgically. This study reviewed our experiences in
      the surgical management of mycotic aortic aneurysms. Methods: In total, 26
      patients who underwent surgery for a mycotic aneurysm were retrospectively
      reviewed. The mycotic aneurysms involved the thoracic aorta in 9 patients, the
      thoracoabdominal aorta in 4 patients, and the abdominal aorta in 13 patients. An
      overt aortic rupture in the mediastinum or retroperitoneal space was detected in
      4 patients. Patients were classified into one of two groups, febrile or afebrile,
      and background characteristics, surgical intervention, and early and late
      mortalities were all compared. Results: There were 19 patients who underwent open
      surgery, and 7 patients underwent endovascular repair. No significant differences
      in the clinical characteristics were found between the two groups; however, the
      incidence of postoperative complications was significantly higher in the febrile
      group than in the afebrile group (P=0.024). Overall mortality was 15.4% (4/26),
      and 30-day mortality was 7.7% (2/26). Conclusion: Although febrile patients had a
      higher incidence of postoperative complications, surgical mortality from a
      mycotic aneurysm was within an acceptable range. Each patient should be
      thoroughly evaluated and treated on a case-by-case basis, using conventional open
      repair, endovascular repair, or a combination of both approaches.

PMID- 29034018
TI  - Bailout Endovascular Stent Grafting for an Ascending Aortic Pseudoaneurysm Using
      an Infrarenal Aortic Extension Cuff.
AB  - We report successful thoracic endovascular repair of a pseudoaneurysm rupture in
      the ascending aorta using infrarenal endovascular devices after an aortic valve
      replacement. Complete exclusion of the pseudoaneurysm was achieved with no
      endoleak or postoperative complications. Despite limitations of the current
      technology, this endovascular technique was a relatively less invasive, feasible
      lifesaving surgical option for the repair of a pseudoaneurysm of the ascending
      aorta with a diameter <=32 mm.

PMID- 29034020
TI  - Persistent Sciatic Artery Aneurysm with Limb Ischemia: A Report of Two Cases.
AB  - We report two cases of persistent sciatic artery (PSA) aneurysm with limb
      ischemia. Physicians who treat peripheral artery disease should be aware that PSA
      is a very rare congenital malformation of the lower extremities that is
      potentially hazardous, and that revascularization should be performed when a PSA
      aneurysm is treated.

PMID- 29034019
TI  - Hybrid Repair of an Abdominal Aortic Aneurysm: Debranching with Endovascular
      Aneurysm Repair in a Patient with Horseshoe Kidney.
AB  - Abdominal aortic aneurysm (AAA) with associated horseshoe kidney (HSK) poses a
      technical challenge when performing conventional open surgical repair because of
      possible complications including renal infarction, neuralgia, and collecting
      system disruption. Endovascular aortic repair (EVAR) is considered the first-line
      treatment for this pathology, allowing for aneurysm repair without isthmus
      bisection. However, whether to sacrifice commonly presenting aberrant renal
      arteries during EVAR is a point of controversy. We report a case in which hybrid
      repair was performed for AAA to preserve aberrant renal vasculature in a patient
      with HSK.

PMID- 29034021
TI  - Endovascular Repair for Kommerell's Diverticulum and Right-Sided Aortic Arch.
AB  - A 74-year-old man with hoarseness was diagnosed with a right-sided aortic arch
      and Kommerell's diverticulum by computed tomography (CT). The diverticulum had a
      maximum diameter of 33 mm, and surgical intervention was chosen because of the
      possibility of rupture. A right common carotid to right subclavian artery bypass
      was constructed, stent-graft was placed after the branching of the right common
      carotid artery, and coil embolization of the diverticulum was performed via left
      brachial artery. No leaks were found on postoperative CT. Symptoms disappeared
      and the diverticulum became smaller soon after surgery. Thoracic endovascular
      aortic repair (TEVAR) for Kommerell's diverticulum was safe and effective.

PMID- 29034022
TI  - Mediastinal Perigraft Seroma after Repair of Type A Dissection with a Polyester
      Graft.
AB  - Perigraft seromas are uncommon after surgical repair of the thoracic aorta with
      woven polyester grafts. A 50-year-old woman required redo sternotomy for the
      treatment of a perigraft seroma 6 months after total arch replacement for acute
      type A dissection. After removal of a jelly-like mass, a prosthetic graft was
      covered with fibrin glue, and the bilateral pleurae beside the graft were opened
      widely for drainage of effusion into the bilateral pleural cavities. Bacterial
      culture and laboratory and histological examination of the content confirmed the
      final diagnosis of perigraft seroma. No evidence of recurrence was observed 4
      months after drainage.

PMID- 29034023
TI  - Retrograde Ascending Aortic Dissection after Stent Grafting for Stanford Type B
      Aortic Dissection with Severe Limb Ischemia.
AB  - We report a rare case of retrograde Stanford type A aortic dissection after
      endovascular repair for complicated Stanford type B aortic dissection. A 45-year
      old man presented with a sudden onset of back pain and was transferred to our
      hospital. Computed tomography demonstrated acute Stanford type B aortic
      dissection with lower limb ischemia. Emergency endovascular surgery was planned
      for repair of the Stanford type B aortic dissection. The patient suddenly
      developed recurrent chest pain 10 days after the initial procedure. Computed
      tomography revealed retrograde Stanford type A aortic dissection involving the
      ascending aorta and aortic arch. The patient underwent a successful emergency
      total aortic arch replacement.

PMID- 29034024
TI  - Successful Complete Surgical Resection of a Large Venous Malformation of the
      Lower Extremity: A Case Report.
AB  - Venous malformations (VMs) are the most common type of vascular malformations,
      resulting from errors in vascular morphogenesis. Because of the wide variety in
      their presentations, selecting the appropriate treatment, especially for large
      VMs, may be challenging. Herein, we report a case of a 59-year-old man with a
      large VM in the lower extremity who achieved favorable outcomes by complete
      surgical resection. Even large VMs can be successfully treated with surgery when
      patients are properly selected. An accurate and careful evaluation is essential
      for achieving optimal outcome in patients with VMs.

PMID- 29034025
TI  - Replacement of the Thoracoabdominal Aorta after Endovascular Abdominal Aneurysm
      Repair for Ruptured Infected Aneurysm: A Case Report.
AB  - A 73-year-old man underwent emergency endovascular abdominal aneurysm repair
      (EVAR) for a ruptured infected abdominal aortic aneurysm. Two years after EVAR,
      he was admitted with a spiking fever and left lower back pain. Computed
      tomography scan revealed not only recurrent graft infection with psoas abscess
      but also infection around the orifice of the superior mesenteric artery. Because
      conservative medical therapy with antibiotics could not control the infection, we
      performed complete removal of the infected stent graft, debridement of psoas
      abscess, and in situ replacement of the thoracoabdominal aorta using rifampicin
      soaked prosthetic grafts, followed by the omental flap. He was discharged with no
      complications.

PMID- 29034026
TI  - Invaginated Graft Insertion Anastomosis for a Type Ib Endoleak at the Supraceliac
      Aorta Following Thoracic Endovascular Aortic Repair.
AB  - Open surgery for a type Ib endoleak after thoracic endovascular aortic repair is
      associated with some knacks and pitfalls, particularly in cases wherein the
      distal edge of a stent graft is located at just supraceliac aorta and the
      renovisceral segment and infrarenal aorta do not require surgical intervention.
      Here we describe the invaginated graft insertion technique to provide an easy and
      secure anastomosis in such clinical situations. This procedure may be feasible
      for anastomosis between a prosthetic vascular graft and a previously deployed
      stent graft when the location of the anastomosis is distant from the surface of
      the skin incision with a narrow and limited surgical view.

PMID- 29034029
TI  - ERRATUM.
AB  - [This corrects the article on p. 267 in vol. 9.].

PMID- 29034028
TI  - Endovascular Treatment for Kommerell's Diverticulum with a Right-Sided Aortic
      Arch.
AB  - We report a rare case of type A dissection involving a right-sided aortic arch
      with an aberrant left subclavian artery originating from Kommerell's diverticulum
      in a 76-year-old woman. Endovascular treatment for Kommerell's diverticulum
      including intimal tear of the dissection was performed. At the 5-year follow-up,
      the patient was doing well, with no endoleak or dilatation of the Kommerell's
      diverticulum.

PMID- 29034027
TI  - Retrograde Use of Frontrunner Catheter in Superficial Femoral Artery for Flushing
      Long Segment Occlusions Involving Distal Common Femoral Artery.
AB  - We present the case of an 81-year-old female with flush occlusion of the
      superficial femoral artery (SFA) and percutaneous transluminal angioplasty.
      Initially, the antegrade approach failed due to flush occlusion without stump.
      Hard, round surfaced, calcific, and eccentric plaque of the ostium of SFA was
      also present, which involved distal common femoral artery (CFA). Thus, we
      successfully used a Frontrunner catheter for retrograde reentry at the lower
      position of the CFA. Various treatment strategies involving Frontrunner and
      atherectomy devices could make percutaneous procedures possible in
      femoropopliteal occlusive disease, involving the CFA.

PMID- 29034030
TI  - ERRATUM.
AB  - [This corrects the article on p. 277 in vol. 9.].

PMID- 29034031
TI  - Coronary Artery Bypass Surgery in End-Stage Renal Disease Patients.
AB  - The number of patients requiring hemodialysis is continuously increasing around
      the world. Hemodialysis affects patient quality of life and it is also associated
      with a higher risk for cardiovascular events. In addition to traditional risk
      factors for cardiovascular events such as hypertension, hyperlipidemia, and
      diabetes, hemodialysis is associated with hyperphosphatemia, chronic
      inflammation, vascular calcification, and anemia which accelerate
      atherosclerosis, vascular stiffness, and cardiac ischemia. Treatment strategy for
      coronary revascularization in this progressive disease remains controversial.
      However, a systematic treatment including medical therapy and complete
      revascularization through a less invasive strategy should be considered in
      addressing this problem. This review discusses the epidemiology, vascular
      pathology and current treatment options in patients with end-stage renal disease
      requiring coronary revascularization.

PMID- 29034033
TI  - Novel Anticoagulant Therapy of Venous Thromboembolism: Current Status and Future
      Directions.
AB  - The first-line treatment of venous thromboembolisms (VTE) is anticoagulant
      therapy, and unfractionated heparin and warfarin are used in Japan. However, as
      both drugs require dosage adjustments that are difficult, VTE recurrences occur
      relatively frequently, and hemorrhagic complications are extremely common. The
      parenteral factor Xa inhibitor fondaparinux and the direct oral anticoagulants
      (DOACs) edoxaban, rivaroxaban, and apixaban have recently become available as
      treatments for VTE in Japan. These novel anticoagulants have more stable effects
      than traditional therapies and are thus considered safer and more effective than
      the traditional agents. Especially, DOACs offer improved long-term prevention of
      recurrence in patients with unprovoked VTE. The initiation of DOAC monotherapy
      soon after VTE onset leads to shorter hospital stays than required with the older
      therapies and allows for outpatient treatment. DOACs have additional benefits,
      such as safer anticoagulant therapy for cancer patients. These novel
      anticoagulants are extremely promising, but there is a current lack of evidence
      in areas such as dosing regimens for highly vulnerable patients and dosing for
      long-term use, and alternative regimens for each DOAC.

PMID- 29034032
TI  - Current Perspective on Hemodialysis Patients with Peripheral Artery Disease.
AB  - The prevalence of peripheral artery disease is substantially higher in patients
      on chronic hemodialysis than in the general population. The presence of calcified
      lesions characteristic of hemodialysis patients has an adverse influence on the
      initial success and long-term outcomes of both surgical bypass and endovascular
      therapy. Although the selection of revascularization strategy depends on whether
      an autologous vein is available and if the patient has a life expectancy of at
      least two years, it is difficult to predict the life expectancy in a real-world
      clinical situation. Endovascular therapy may be appropriate for many hemodialysis
      patients with poor general condition because of the high risk of perioperative
      complications and the poor long-term prognosis. Deciding which treatment option
      is more appropriate should be done on a case-by-case basis, especially in
      hemodialysis patients with critical limb ischemia.

PMID- 29034034
TI  - Pathophysiology of Venous Thromboembolism with Respect to the Anatomical Features
      of the Deep Veins of Lower Limbs: A Review.
AB  - Here the pathophysiology of venous thromboembolism is reviewed with respect to
      the anatomical features of the deep veins of lower limbs. A thrombus is less
      likely to form in the thigh veins compared with that in the calf veins; however,
      clinical symptoms are more likely to appear in the thigh veins owing to vascular
      occlusion. When a patient is bedridden, thrombosis is more likely to occur in the
      intramuscular vein, which mainly depends on muscular pumping and the venous
      valve, rather than in the three crural branches, which mainly depends on the
      pulsation of the accompanying artery. Thrombi are prone to be generated in the
      soleal vein compared with those in the gastrocnemius vein because of the vein and
      muscle structures. A soleal vein thrombosis grows toward the proximal veins along
      the drainage veins. To prevent a sudden pulmonary thromboembolism-related death
      in bedridden patients, preventing soleal vein thrombus formation and observing
      the thrombus proximal propagation via the drainage veins are clinically
      important. When deep vein thrombosis occurs, avoiding embolization and sequela
      caused by the thrombus organization is necessary.

PMID- 29034036
TI  - Intervention for Varicose Veins of Lower Extremities Lowers the Brain Natriuretic
      Peptide Values in Varicose Vein Patients.
AB  - Objective: To evaluate the relationship between varicose veins and heart failure,
      both of which cause edema of lower extremities. Materials and Methods: We
      enrolled 150 patients who underwent intervention for varicose veins of lower
      extremities between December 2012 and October 2015, and perioperative data were
      retrospectively investigated. Results: Of the 150 patients, 104 (69.3%) were
      females. The mean age was 66.8+/-10.6 years (27-85 years). Eighty (53.3%)
      patients had varicose veins in both legs. In all patients, the postoperative
      (brain natriuretic peptide (BNP) value was significantly lower than the
      preoperative BNP value (pre : post=39.3 : 30.5 pg/dl, P<0.0001). In patients with
      higher BNP values (>100 pg/dl), the postoperative BNP values were significantly
      lower than the preoperative BNP values (pre : post=192.7 : 166.1 pg/dl,
      P<0.0001). Body weights of the patients decreased differently between pre- and
      post-operation (pre : post=61.3 : 59.4 kg, P=0.0008). Conclusion: Intervention
      for varicose veins of lower extremities might be considered clinically useful for
      the improvement of cardiac function.

PMID- 29034035
TI  - Surgical Embolectomy for Acute Pulmonary Thromboembolism.
AB  - Acute pulmonary thromboembolism is a catastrophic event, especially for
      hospitalized patients. The prognosis of pulmonary thromboembolism depends on the
      degree of pulmonary arterial occlusion. The mortality of massive pulmonary
      embolism is reportedly as high as 25% without cardiopulmonary arrest and 65% with
      cardiopulmonary arrest. In patients with unstable hemodynamics due to pulmonary
      thromboembolism, surgical pulmonary embolectomy is indicated for patients with a
      contraindication to thrombolysis, failed catheter therapy, or failed
      thrombolysis. Thrombolytic therapy adds an additional burden on patients who are
      at risk of potential hemorrhagic complications. It is also indicated if patients
      are already on a veno-arterial extra-corporate membrane oxygenator for
      circulatory collapse or cardiopulmonary arrest. The outcome for patients who
      require cardiopulmonary resuscitation for longer than 30 minutes is poor.
      Therefore, early triage for massive and sub-massive pulmonary embolism is
      crucial. A team approach including a cardiovascular surgeon may be effective to
      save critically ill patients. Prompt removal of emboli reduces the right
      ventricular load with quick recovery of cardiopulmonary function in the early
      postoperative period. A recent series reported excellent results, with in
      hospital mortality of less than 10%. Surgical pulmonary embolectomy is an
      effective, safe, and easy procedure to save critical patients due to pulmonary
      thromboembolism.

PMID- 29034037
TI  - Characteristics of Abdominal Aortic Aneurysm in Japanese Patients Aged 50 Years
      or Younger.
AB  - Objective: We investigated the characteristics and surgical outcomes of abdominal
      aortic aneurysm (AAA), which typically occurs in elderly persons, in Japanese
      patients aged 50 years or younger. Materials and Methods: Clinical records of 999
      patients who underwent open or endovascular repair for AAA at our hospital
      between 2007 and 2015 were reviewed to identify the clinical characteristics and
      surgical outcomes of young patients with AAA. The cohort included 14 patients
      aged 50 years or younger (mean, 40.4 years; young group) and 985 patients aged
      older than 50 years (mean, 72.8 years; old group). Results: Marfan syndrome,
      prior aortic dissection, and a history of aortic surgery were more prevalent in
      the young group, and 50% of the patients in the young group had dissecting
      aneurysms. All patients in the young group underwent open repair. Overall in
      hospital mortality rates were 7.1% (1/14) and 1.9% (19/985) in the young and old
      groups, respectively (P=0.67). Seven-year survival and aortic event-free survival
      rates in the young group were 82.5%+/-11.5%, and 71.2+/-14.5%, respectively.
      Conclusion: AAA in patients aged 50 years or younger tended to be associated with
      Marfan syndrome, a history of aortic surgery, and prior aortic dissection. Early
      outcomes of AAA among young patients are acceptable, but close postoperative
      monitoring is important.

PMID- 29034038
TI  - Catheter-Directed Thrombolysis in the Treatment of Acute Ischemia in Lower
      Extremities Is Safe and Effective, Especially with Concomitant Endovascular
      Treatment.
AB  - Objective: To evaluate the influence of pre-procedural characteristics on
      immediate and late results as well as the safety of catheter-directed
      thrombolysis (CDT) in acute ischemia of the lower extremity. Materials and
      Methods: A retrospective study comprising 249 patients treated by CDT from
      January 2006 to December 2012. Outcomes were primary patency, haemorrhagic
      complications, amputation and mortality. Results: Primary patency for CDT alone
      was 68%, for CDT plus endovascular treatment 87% and for successful CDT with
      supplementary surgery 62% giving an overall primary patency of 76%. Two (0.8%)
      patients suffered from cerebral haemorrhage during CDT. We found a significant
      correlation between 30 day amputation rate and no visual distal run-off at CDT
      start (OR 2.31; CI95% 1.09-4.91; p-value=0.02) and onset of symptoms to CDT start
      of 8-14 days (OR 4.09; CI95% 1.42-11.81; p-value=0.01). Lack of visualized distal
      run-off was also associated with a significant risk of 30 day mortality (OR 5.84;
      CI95% 1.26-27.00; p-value=0.02). Conclusion: Our results show that CDT is a
      feasible and safe treatment option especially when combined with angioplasty +/-
      stent. However, no distal run-off at primary angiography is associated with
      higher rates of amputation during follow-up and 30 day mortality.

PMID- 29034039
TI  - Histological Reactions and the In Vivo Patency Rates of Small Silk Vascular
      Grafts in a Canine Model.
AB  - Objective: To evaluate in vivo patency rates of silk fibroin (SF) vascular grafts
      and resulting histological reactions in a canine model. Methods: To generate 3.5
      mm inner diameter vessels, a combination of plaited silk fibers were wound with
      cocoon filaments and subsequently coated with an SF solution. The resulting SF
      grafts (n=35) were implanted into the carotid arteries of male beagles (age, 1-2
      years; body weight: 9.0-10.5 kg). Expanded polytetrafluoroethylene (4-mm inner
      diameter, ePTFE) grafts (n=5) were used as controls. Graft patency was monitored
      via ultrasonography with histological changes analyzed via microscopic
      examination. Results: Compared with animals that received the ePTFE grafts,
      animals that received SF grafts exhibited the same thickness of luminal layers
      and fibrin accumulation and collagen fiber replacement with endothelialization at
      3 months post-implantation via histological examination. The patency rates of the
      SF and the ePTFE grafts at 6 months post-implantation were 7.8% and 0%,
      respectively. Conclusion: This canine model study demonstrated that SF grafts
      induce unique histological reactions but fail to achieve long-term patency.

PMID- 29034040
TI  - Infected Thoracic Aortic Aneurysm Caused by Helicobacter cinaedi.
AB  - The causative organism is not identified in some cases of infected aneurysms, a
      life-threatening condition. A 68-year-old man presented with chest/back pain and
      a 1-year history of intermittent fever and fatigue. Computed tomography revealed
      a thoracic aortic aneurysm. After several negative blood cultures, he was
      eventually diagnosed with an infected aneurysm caused by Helicobacter cinaedi via
      gene analysis of an aortic tissue specimen. As H. cinaedi is a low-virulence
      bacterium, infection with this pathogen should be suspected in cases of aortic
      aneurysms with unidentified causative organism and a long history of subjective
      symptoms. Detailed examinations, including polymerase chain reaction, should be
      conducted in such cases.

PMID- 29034041
TI  - Successful Endovascular Repair of Mycotic Aortic Pseudoaneurysm Followed by
      Aortoesophageal Fistula.
AB  - Mycotic aneurysm of the aorta is a rare, but life-threatening pathology. In
      recent years, endovascular stent graft placement has been introduced as an
      effective alternative for treating infected aortic aneurysms. A 64-year-old woman
      with a history of paraplegia due to spinal cord injury was referred to our
      institute with fever and blood-tinged sputum. Computed tomography (CT) scan
      showed an 11-cm pseudoaneurysm arising from the proximal descending aorta, which
      was normal 1 month ago at the previous CT scan. The patient underwent thoracic
      endovascular aortic repair for the pseudoaneurysm, deployed with a transiliac
      access approach, and received antibacterial medical therapy. On postoperative day
      11, she developed signs of infection, caused by an aortoesophageal fistula. The
      infection was treated conservatively with parenteral nutrition and antibiotic
      administration. The patient had an uneventful recovery and was discharged on
      postoperative day 113. At 2-year follow-up, she had a normal physical examination
      and CT angiography showed a marked reduction of the pseudoaneurysm sac. We report
      a successful endovascular stent grafting and subsequent medical treatment in a
      patient with a mycotic thoracic aortic pseudoaneurysm followed by a postoperative
      aortoesophageal fistula.

PMID- 29034042
TI  - Description of the Surgical Strategy Used for the Treatment of a Complex Disease:
      Report of a Case.
AB  - We report a rare case in which a patient required three surgeries with competing
      priorities. In a 68-year-old man diagnosed with an abdominal aortic aneurysm
      (AAA), computed tomography (CT) revealed an infrarenal AAA, unusual thickening of
      the sigmoid colon that suggested cancer, and a filling defect in the left atrium.
      We considered the disease stage, which affects prognosis, and the risk of
      complications that could interfere with the treatment of the other pathologies
      and developed a three-stage surgical strategy: (i) endovascular aortic repair,
      (ii) sigmoid colectomy, and (iii) resection of the left atrial mass. The
      patient's postsurgical recovery was uneventful.

PMID- 29034043
TI  - Suture Line Dehiscence after Endovascular Aneurysm Repair in a Patient with
      Marfan Syndrome.
AB  - A 68-year-old man with Marfan syndrome developed de-novo leakage after
      endovascular aneurysm repair of a Dacron graft. Findings at subsequent
      reoperation suggested that the rebound force on the endograft generated by marked
      longitudinal deformation in the Dacron graft may have placed stress on the suture
      line, leading to partial dehiscence. The Dacron graft seemed to provide a stable
      proximal landing zone. However, the strong tendency of some endograft devices to
      return to their original shape may apply stress that affected weakened regions of
      the native aorta.

PMID- 29034044
TI  - Bronchial Artery Aneurysm Treated Using Aortic Stent Graft Alone: A Case Report.
AB  - A 72-year-old woman with a history of malignant lymphoma was referred to our
      hospital for the treatment of a bronchial artery aneurysm. Computed tomography
      (CT) scan showed a round, 30 mm-diameter fusiform aneurysm with two tortuous
      inflow arteries. We deployed thoracic stent grafting to cover the orifice of the
      two inflow arteries without transcatheter bronchial arterial embolization.
      Postoperative CT scan revealed complete thrombosis of the aneurysm. Although
      further follow-up is mandatory, this may be considered a viable treatment option
      in cases wherein the bronchial artery aneurysm is anatomically difficult to
      treat.

PMID- 29034045
TI  - Severe Obstructive Calcification of the Descending Aorta: A Case Report of "Coral
      Reef Aorta".
AB  - An 82-year-old man suffering from lower back pain and dyspnea presented to our
      institute in a state of shock. Computed tomography showed subtotal occlusion of
      the descending aorta with massive atherosclerotic calcification. As the proximal
      portion of the superior mesenteric artery was obstructed, emergency bypass from
      the right axillary artery to the bilateral external iliac arteries was performed,
      but the patient died 2 days later. Autopsy revealed that reddish-brown and
      verrucous masses obstructed the descending aorta, and high-grade thickening of
      the intima and extensive deposits of calcium in the lumina and medial layer were
      detected in the descending aorta histologically.

PMID- 29034046
TI  - In Situ Reconstruction with Extended Debridement in Patients with Mycotic
      Abdominal Aortic Aneurysms.
AB  - The surgical outcomes in patients with mycotic aortic aneurysm are still poor. In
      situ reconstruction and extra-anatomical bypass are the 2 main surgical options
      used in these patients, both of which have postoperative complications:
      recurrence of infection and aortic stump blowout, respectively. We performed in
      situ reconstruction in 25 consecutive patients with mycotic abdominal aortic
      aneurysms together with extended debridement using an irrigation device, omental
      flap coverage, rifampicin-soaked prosthetic graft, and sufficient antibiotics
      administration. There were 3 in-hospital mortalities; however, no infection- or
      procedure-related adverse events were observed in other cases during the mid-term
      follow-up period.

PMID- 29034048
TI  - Northeastern Section of the American Urological Association 69th Annual Meeting,
      Savannah, GA: Scientific Program.

PMID- 29034047
TI  - Processing of Internal and External Signals for Performance Monitoring in the
      Context of Emotional Faces.
AB  - Performance monitoring can be based on internal or external signals. We recorded
      event-related potentials (ERPs) to investigate whether relating performance to
      external signals affects internal performance monitoring. Thirty participants
      performed a task in which responses were followed by faces whose expressions were
      partially contingent upon performance. Instructions given to half of the
      participants mentioned a link between task performance and the upcoming face
      expression. Instructed participants showed smaller error-related negativity
      (Ne/ERN) to erroneous responses and larger N170 to faces as compared to
      participants in the not-instructed group. In addition, we observed a correlation
      between DeltaNe/ERN and P1-latency benefit for angry faces after errors. Taken
      together, processing of internally generated signals for performance monitoring
      is reduced by instructions referring to an emotional face. Furthermore, we relate
      the correlation between the magnitude of internal monitoring and facilitation in
      processing angry faces to priming induced by the negative affective meaning of
      errors.

PMID- 29034049
TI  - Postmortem Toxicology Findings of Acetyl Fentanyl, Fentanyl, and Morphine in
      Heroin Fatalities in Tampa, Florida.
AB  - In the last two years, an epidemic of 40 fatal heroin overdose cases has occurred
      in the Tampa area of Florida. Of these cases, 14 involved fentanyl and acetyl
      fentanyl. Victim demographics, case histories, toxicology findings, and causes
      and manners of death for all 40 deaths are presented. In 26 deaths in which
      acetyl fentanyl or fentanyl were not involved, free and total peripheral blood
      morphine concentrations were consistent with fatal heroin intoxications,
      averaging 0.16 mg/L and 0.35 mg/L, respectively. In the heroin cases with
      fentanyl present (n=7), the average free morphine concentration was 0.040 mg/L,
      the average total morphine concentration was 0.080 mg/L, and the average fentanyl
      concentration was 0.012 mg/L. In the cases with heroin, fentanyl, and acetyl
      fentanyl (n=3), the average free morphine concentration was 0.010 mg/L, the
      average total morphine concentration was 0.030 mg/L, the average fentanyl
      concentration was 0.018 mg/L, and the average acetyl fentanyl concentration was
      0.008 mg/L. In the cases involving only acetyl fentanyl (without heroin or
      fentanyl, n=4), the average acetyl fentanyl concentration was 0.47 mg/L and the
      average acetyl norfentanyl concentration was 0.053 mg/L. The presented cases,
      with associated drug concentrations, case histories, demographics, and causes and
      manners of death may help provide assistance with the interpretation of the
      postmortem findings. Based on case circumstances, autopsy results, and toxicology
      results, it is evident that fentanyl and/or acetyl fentanyl, when present,
      contributed to the cause of death.

PMID- 29034050
TI  - Separation of sperm cells from samples containing high concentrations of white
      blood cells using a spiral channel.
AB  - Microfluidic technology has potential to separate sperm cells from unwanted
      debris while improving the effectiveness of assisted reproductive technologies
      (ART). Current clinical protocol limitations regarding the separation of sperm
      cells from other cells/cellular debris can lead to low sperm recovery when the
      sample contains a low concentration of mostly low motility sperm cells and a high
      concentration of unwanted cells/cellular debris, such as in semen samples from
      patients with pyospermia [high white blood cell (WBC) semen]. This study
      demonstrates label-free separation of sperm cells from such semen samples using
      inertial microfluidics. The approach does not require any externally applied
      forces except the movement of the fluid sample through the instrument. Using this
      approach, it was possible to recover not only any motile sperm, but also viable
      less-motile and non-motile sperm cells with high recovery rates. Our results
      demonstrate the ability of inertial microfluidics to significantly reduce WBC
      concentration by flow focusing of target WBCs within a spiral channel flow. The
      estimated sample process time was more rapid (~5 min) and autonomous than the
      conventional method (gradient centrifuge sperm wash; ~1 h). A mixture of
      sperm/WBC was injected as the device input and 83% of sperm cells and 93% of WBCs
      were collected separately from two distinct outlets. The results show promise for
      enhancing sperm samples through inertial flow processing of WBCs and sperm cells
      that can provide an advantage to ART procedures such as sample preparation for
      intrauterine insemination.

PMID- 29034051
TI  - On-chip cell labelling and washing by capture and release using microfluidic trap
      arrays.
AB  - Flow cytometry analysis requires a large amount of isolated, labelled, and
      purified cells for accurate results. To address the demand for a large quantity
      of cells prepared in a timely manner, we describe a novel microfluidic trap
      structure array for on-chip cell labelling, such as intracellular and
      extracellular labelling, and subsequent washing and release of cells. Each device
      contains [Formula: see text] trap structures, which made the preparation of large
      numbers of cells [Formula: see text] possible. The structure has a streamlined
      shape, which minimizes clogging of cells in capture and release steps. The trap
      structure arrays are built and tested using leukocytes, with different load flow
      speeds, incubation times, and release flow speeds. ~85% of cells are captured
      independent of the input flow speed. The release efficiency depends on the
      incubation time, with over ~80% of captured cells released for up to 20 min
      incubation, and on-chip labelling and washing with STYO13 are demonstrated.
      Qualitative models are developed as guidance for designing the proposed trap
      structure and to explain the increased performance over previous approaches.

PMID- 29034052
TI  - Microfluidic cell concentrator with a reduced-deviation-flow herringbone
      structure.
AB  - In this study, a microfluidic cell concentrator with a reduced-deviation-flow
      herringbone structure is proposed. The reduced-deviation-flow herringbone
      structure reduces the magnitude of deviation flow by a factor of 3.3 compared to
      the original herringbone structure. This structure shows higher recovery
      efficiency compared to the original herringbone structure for various particle
      sizes at high flow rate conditions. Using the reduced-deviation-flow herringbone
      structure, the experimental results show a recovery efficiency of 98.5% and a
      concentration factor of 3.4* at a flow rate of 100 ml/h for all particle sizes.
      An iterative concentration process is performed to achieve a higher concentration
      factor for 10.2-MUm particles and Jurkat cells. With two stages of the
      concentration process, we were able to achieve over 98% recovery efficiency and a
      concentration factor of 10-11*. Cell viability was found to be above 96% after
      iterative concentration. We believe that this device could be used to concentrate
      cells as a preparatory step for studying low-abundance cells.

PMID- 29034053
TI  - A 3D-printed microbial cell culture platform with in situ PEGDA hydrogel barriers
      for differential substrate delivery.
AB  - Additive manufacturing, or 3D-printing techniques have recently begun to enable
      simpler, faster, and cheaper production of millifluidic devices at resolutions
      approaching 100-200 MUm. At this resolution, cell culture devices can be
      constructed that more accurately replicate natural environments compared with
      conventional culturing techniques. A number of microfluidics researchers have
      begun incorporating additive manufacturing into their work, using 3D-printed
      devices in a wide array of chemical, fluidic, and even some biological
      applications. Here, we describe a 3D-printed cell culture platform and
      demonstrate its use in culturing Pseudomonas putida KT2440 bacteria for 44 h
      under a differential substrate gradient. Polyethylene glycol diacrylate (PEGDA)
      hydrogel barriers are patterned in situ within a 3D-printed channel. Transport of
      the toluidine blue tracer dye through the hydrogel barriers is characterized.
      Nutrients and oxygen were delivered to cells in the culture region by diffusion
      through the PEGDA hydrogel barriers from adjacent media or saline perfusion
      channels. Expression of green fluorescent protein by P. putida KT2440 enabled
      real time visualization of cell density within the 3D-printed channel, and
      demonstrated cells were actively expressing protein over the course of the
      experiment. Cells were observed clustering near hydrogel barrier boundaries where
      fresh substrate and oxygen were being delivered via diffusive transport, but
      cells were unable to penetrate the barrier. The device described here provides a
      versatile and easy to implement platform for cell culture in readily controlled
      gradient microenvironments. By adjusting device geometry and hydrogel properties,
      this platform could be further customized for a wide variety of biological
      applications.

PMID- 29034054
TI  - Tumor cell capture patterns around aptamer-immobilized microposts in microfluidic
      devices.
AB  - Circulating tumor cells (CTCs) have shown potential for cancer diagnosis and
      prognosis. Affinity-based CTC isolation methods have been proved to be efficient
      for CTC detection in clinical blood samples. One of the popular choices for
      affinity-based CTC isolation is to immobilize capture agents onto an array of
      microposts in microchannels, providing high CTC capture efficiency due to
      enhanced interactions between tumor cells and capture agents on the microposts.
      However, how the cells interact with microposts under different flow conditions
      and what kind of capture pattern results from the interactions have not been
      fully investigated; a full understanding of these interactions will help to
      design devices and choose experimental conditions for higher CTC capture
      effeciency. We report our study on their interaction and cell distribution
      patterns around microposts under different flow conditions. Human acute
      lymphoblastic leukemia cells (CCRF-CEM) were used as target cancer cells in this
      study, while the Sgc8 aptamer that has specific binding with CCRF-CEM cells was
      employed as a capture agent. We investigated the effects of flow rates and
      micropost shapes on the cell capture efficiency and capture patterns on
      microposts. While a higher flow rate decreased cell capture efficiency, we found
      that the capture pattern around microposts also changed, with much more cells
      captured in the front half of a micropost than at the back half. We also found
      the ratio of cells captured on microposts to the cells captured by both
      microposts and channel walls increased as a function of the flow rate. We
      compared circular microposts with an elliptical shape and found that the geometry
      affected the capture distribution around microposts. In addition, we have
      developed a theoretical model to simulate the interactions between tumor cells
      and micropost surfaces, and the simulation results are in agreement with our
      experimental observation.

PMID- 29034055
TI  - A STATISTICAL MODEL TO ASSESS (ALLELE-SPECIFIC) ASSOCIATIONS BETWEEN GENE
      EXPRESSION AND EPIGENETIC FEATURES USING SEQUENCING DATA.
AB  - Sequencing techniques have been widely used to assess gene expression (i.e., RNA
      seq) or the presence of epigenetic features (e.g., DNase-seq to identify open
      chromatin regions). In contrast to traditional microarray platforms, sequencing
      data are typically summarized in the form of discrete counts, and they are able
      to delineate allele-specific signals, which are not available from microarrays.
      The presence of epigenetic features are often associated with gene expression,
      both of which have been shown to be affected by DNA polymorphisms. However, joint
      models with the flexibility to assess interactions between gene expression,
      epigenetic features and DNA polymorphisms are currently lacking. In this paper,
      we develop a statistical model to assess the associations between gene expression
      and epigenetic features using sequencing data, while explicitly modeling the
      effects of DNA polymorphisms in either an allele-specific or nonallele-specific
      manner. We show that in doing so we provide the flexibility to detect
      associations between gene expression and epigenetic features, as well as
      conditional associations given DNA polymorphisms. We evaluate the performance of
      our method using simulations and apply our method to study the association
      between gene expression and the presence of DNase I Hypersensitive sites (DHSs)
      in HapMap individuals. Our model can be generalized to exploring the
      relationships between DNA polymorphisms and any two types of sequencing
      experiments, a useful feature as the variety of sequencing experiments continue
      to expand.

PMID- 29034056
TI  - Effects of Sterilization on Shape Memory Polyurethane Embolic Foam Devices.
AB  - Polyurethane shape memory polymer (SMP) foams have been developed for various
      embolic medical devices due to their unique properties in minimally invasive
      biomedical applications. These polyurethane materials can be stored in a
      secondary shape, from which they can recover their primary shape after exposure
      to an external stimulus, such as heat and water exposure. Tailored actuation
      temperatures of SMPs provide benefits for minimally invasive biomedical
      applications, but incur significant challenges for SMP-based medical device
      sterilization. Most sterilization methods require high temperatures or high
      humidity to effectively reduce the bioburden of the device, but the environment
      must be tightly controlled after device fabrication. Here, two probable
      sterilization methods (nontraditional ethylene oxide (ntEtO) gas sterilization
      and electron beam irradiation) are investigated for SMP medical devices. Thermal
      characterization of the sterilized foams indicated that ntEtO gas sterilization
      significantly decreased the glass transition temperature. Further material
      characterization was undertaken on the electron beam (ebeam) sterilized samples,
      which indicated minimal changes to the thermomechanical integrity of the bulk
      foam and to the device functionality.

PMID- 29034057
TI  - Design and Fabrication of a Low-Cost Three-Dimensional Bioprinter.
AB  - Three-dimensional (3D) bioprinting offers innovative research vectors for tissue
      engineering. However, commercially available bioprinting platforms can be cost
      prohibitive to small research facilities, especially in an academic setting. The
      goal is to design and fabricate a low-cost printing platform able to deliver cell
      laden fluids with spatial accuracy along the X, Y, and Z axes of 0.1 mm. The
      bioprinter consists of three subassemblies: a base unit, a gantry, and a shuttle
      component. The platform utilizes four stepper motors to position along three axes
      and a fifth stepper motor actuating a pump. The shuttle and gantry are each
      driven along their respective horizontal axes via separate single stepper motor,
      while two coupled stepper motors are used to control location along the vertical
      axis. The current shuttle configuration allows for a 5 mL syringe to be extruded
      within a work envelope of 180 mm * 160 mm * 120 mm (X, Y, Z). The shuttle can
      easily be reconfigured to accommodate larger volume syringes. An attachment for a
      laser pen is located such that printing material may be light-activated pre
      extrusion. Positional fidelity was established with calipers possessing a
      resolution to the nearest hundredth millimeter. The motors associated with the X
      and Y axes were calibrated to approximately 0.02 mm per motor impulse. The Z axis
      has a theoretical step distance of ~51 nm, generating 0.04% error over a 10 mm
      travel distance. The A axis, or pump motor, has an impulse distance of 0.001 mm.
      The volume extruded by a single impulse is dictated by the diameter of the
      syringe used. With a 5 mL syringe possessing an inner diameter of 12.35 mm, the
      pump pushes as little as 0.119 MUL. While the Z axis is tuned to the highest
      resolution settings for the motor driver, the X, Y, and A axes can obtain higher
      or lower resolution via physical switches on the motor drivers.

PMID- 29034058
TI  - In Situ Generated Platinum Catalyst for Methanol Oxidation via Electrochemical
      Oxidation of Bis(trifluoromethylsulfonyl)imide Anion in Ionic Liquids at
      Anaerobic Condition.
AB  - The bis(trifluoromethylsulfonyl)imide anion is widely used as an ionic liquid
      anion due to its electrochemical stability and wide electrochemical potential
      window at aerobic conditions. Here we report an innovative strategy by directly
      oxidizing bis(trifluoromethylsulfonyl)imide anion to form a radical
      electrocatalyst on platinum electrode at anaerobic condition. The in situ
      generated radical catalyst was shown to catalytically and selectively promote the
      electrooxidation of methanol to form methoxyl radical, in which the formation
      potential was drastically decreased with the existence of
      bis(trifluoromethylsulfonyl)imide radical. The electrochemically generated
      radical catalyst not only facilitates the oxidation of methanol but also provides
      good selectivity. The unique double layer structure of the 1-butyl-1
      methylpyrrolidinium bis(trifluoromethylsulfonyl)imide ([Bmpy][NTf2]) likely
      excludes the diffusion of larger molar mass molecules onto the electrode surface
      and enables the highly selective methanol oxidation at this IL-electrode
      interface. Cyclic voltammetry (CV) experiments were used to systematically
      characterize the details of the electrochemical processes with and without
      methanol in several other ILs, and a mechanism of the chemical and redox
      processes was proposed. This study provides a promising new approach for
      utilizing the unique properties of ionic liquids not only as solvents and
      electrolytes but also as the medium for in situ generation of electrocatalysts to
      promote methanol redox reactions for practical applications.

PMID- 29034059
TI  - LCN: a random graph mixture model for community detection in functional brain
      networks.
AB  - The aim of this article is to develop a Bayesian random graph mixture model
      (RGMM) to detect the latent class network (LCN) structure of brain connectivity
      networks and estimate the parameters governing this structure. The use of
      conjugate priors for unknown parameters leads to efficient estimation, and a well
      known nonidentifiability issue is avoided by a particular parameterization of the
      stochastic block model (SBM). Posterior computation proceeds via an efficient
      Markov Chain Monte Carlo algorithm. Simulations demonstrate that LCN outperforms
      several other competing methods for community detection in weighted networks, and
      we apply our RGMM to estimate the latent community structures in the functional
      resting brain networks of 185 subjects from the ADHD-200 sample. We find overlap
      in the estimated community structure across subjects, but also heterogeneity even
      within a given diagnosis group.

PMID- 29034060
TI  - Activation of the aryl hydrocarbon receptor and risk of lymphoma subtypes.
AB  - The aryl hydrocarbon receptor (AhR) is a transcription factor implicated in
      several pathways known to be relevant in lymphomagenesis. Aim of our study was to
      explore the link between AhR activation and risk of lymphoma subtypes. We used a
      Dual-Luciferase Assay(r) and a luminometer to detect the activation of the
      luciferase gene, in HepG2 cells transfected with a specific reporter systems, by
      a 50 ml serum aliquot of cases of diffuse large B cell lymphoma (N = 108),
      follicular lymphoma (N = 85), chronic lymphocytic leukemia (N = 72), multiple
      myeloma (N = 80), and Hodgkin lymphoma (N = 94) and 357 controls who participated
      in the multicentre Italian study on gene-environment interactions in lymphoma
      etiology (ItGxE). Risk of each lymphoma subtype associated with AhR activation
      was calculated with polytomous logistic regression adjusting by age, gender, and
      study centre. The overall prevalence of AhR activation ranged 13.9-23.6% by
      subtype, and it varied by study area (8-39%). Risk associated with AhR activation
      was moderately elevated for follicular lymphoma (OR = 1.56, 95% CI 0.86, 2.80)
      and chronic lymphocytic leukemia (OR = 1.56, 95% CI 0.83, 2.96). Despite our
      inconclusive findings about the association with risk of lymphoma subtypes, we
      showed that the Dual-Luciferase Assay can be reliably and easily applied in
      population-based studies to detect AhR activation.

PMID- 29034062
TI  - Brownian motion in confined geometries.
AB  - In a great number of technologically and biologically relevant cases, transport
      of micro- or nanosized objects is governed by both omnipresent thermal
      fluctuations and confining walls or constrictions limiting the available phase
      space. The present Topical Issue covers the most recent applications and
      theoretical findings devoted to studies of Brownian motion under confinement of
      channel-like geometries.

PMID- 29034061
TI  - Association between four SNPs in IL-4 and the risk of gastric cancer in a Chinese
      population.
AB  - Gastric cancer (GC) is the 5th most prevalent cancer. The etiology of GC is still
      poorly understood. We performed a case-control study in a Chinese population to
      investigate the association of rs2243248 (-1098 G/T), rs2227284 (-33 C/T),
      rs2243250 (-589 T/C) and rs2070874 (-107 T/C) polymorphisms and haplotypes with
      the development of gastric cancer in a Chinese population. A total of 362
      patients with gastric cancer and 384 controls were recruited between December
      2013 and December 2015. Genotyping of rs2243248 (-1098 G/T), rs2227284 (-33 C/T),
      rs2243250 (-589 T/C) and rs2070874 (-107 T/C) was performed in a 384-well plate
      format on the sequenom MassARRAY platform, and analyzed by MALDI-TOF MS. The TC
      and CC genotypes of rs2243250 (-589 T/C) were associated with an increased risk
      of gastric cancer when compared with the TT genotype, with adjusted ORs (95% CI)
      of 1.52 (1.07-2.15) and 2.13 (1.30-3.51), respectively. The TTTT haplotype
      revealed a reduced risk of gastric cancer (OR=0.65, 95% CI=0.45-0.94). No linkage
      disequilibrium was found among IL-4 rs2243248, rs2227284, rs2243250 and
      rs2070874. In summary, our findings support a significant association of IL-4
      rs2243250 polymorphism with the risk of gastric cancer in the Chinese population,
      and IL-4 haplotype contributes to the development of this disease.

PMID- 29034063
TI  - Targeting orthotopic gliomas with renal-clearable luminescent gold nanoparticles.
AB  - A major clinical translational challenge in nanomedicine is the potential of
      toxicity associated with the uptake and long-term retention of non-degradable
      nanoparticles (NPs) in major organs. The development of inorganic NPs that
      undergo renal clearance could potentially resolve this significant biosafety
      concern. However, it remains unclear whether inorganic NPs that can be excreted
      by the kidneys remain capable of targeting tumors with poor permeability.
      Glioblastoma multiforme, the most malignant orthotopic brain tumor, presents a
      unique challenge for NP delivery because of the blood-brain barrier and robust
      blood-tumor barrier of reactive microglia and macroglia in the tumor
      microenvironment. Herein, we used an orthotopic murine glioma model to
      investigate the passive targeting of glutathione-coated gold nanoparticles
      (AuNPs) of 3 nm in diameter that undergo renal clearance and 18-nm AuNPs that
      fail to undergo renal clearance. Remarkably, we report that 3-nm AuNPs were able
      to target intracranial tumor tissues with higher efficiency (2.3* relative to
      surrounding non-tumor normal brain tissues) and greater specificity (3.0*) than
      did the larger AuNPs. Pharmacokinetics studies suggested that the higher glioma
      targeting ability of the 3-nm AuNPs may be attributed to the longer retention
      time in circulation. The total accumulation of the 3-nm AuNPs in major organs was
      significantly less (8.4*) than that of the 18-nm AuNPs. Microscopic imaging of
      blood vessels and renal-clearable AuNPs showed extravasation of NPs from the
      leaky blood-tumor barrier into the tumor interstitium. Taken together, our
      results suggest that the 3-nm AuNPs, characterized by enhanced permeability and
      retention, are able to target brain tumors and undergo renal clearance.

PMID- 29034065
TI  - Development of an instrument evaluating the impact of surgeon-patient
      relationship in patients on sick leave.
AB  - Background: To date, no specific instruments exist to measure the quality of the
      patient-surgeon relationship despite its potential to influence clinical and
      economic outcomes in patients undergoing surgery for musculoskeletal disorders
      (MSDs). Objective: The objective was to develop and validate an instrument to
      assess the quality of the patient-surgeon relationship, taking into account the
      return to work after functional restoration surgery. Methods: The instrument
      development was based on literature review, cognitive interviews and expert
      examinations. The instrument's psychometric properties were explored in a sample
      of 50 French patients on sick leave with musculoskeletal disorders or hand
      injuries. Face validity, internal consistency and test-retest reliability were
      evaluated. The dimensionality of the instrument was studied using an exploratory
      principal component analysis. Results: The 11-item instrument showed good
      psychometric properties. The cognitive interviews allowed enhancing the validity
      of the instrument content by capturing patients' point of view. The exploratory
      principal component analysis demonstrated the uni-dimensionality of the
      instrument with the first factor accounting for 83% of the total explained
      variance. Conclusion:This study has developed the first instrument capable of the
      specific assessment of the impact of the surgeon-patient relationship on
      recovery, in patients with hand traumas and MSDs.

PMID- 29034066
TI  - Novel SPECT Technologies and Approaches in Cardiac Imaging.
AB  - Recent novel approaches in myocardial perfusion single photon emission CT (SPECT)
      have been facilitated by new dedicated high-efficiency hardware with solid-state
      detectors and optimized collimators. New protocols include very low-dose (1 mSv)
      stress-only, two-position imaging to mitigate attenuation artifacts, and
      simultaneous dual-isotope imaging. Attenuation correction can be performed by
      specialized low-dose systems or by previously obtained CT coronary calcium scans.
      Hybrid protocols using CT angiography have been proposed. Image quality
      improvements have been demonstrated by novel reconstructions and motion
      correction. Fast SPECT acquisition facilitates dynamic flow and early function
      measurements. Image processing algorithms have become automated with virtually
      unsupervised extraction of quantitative imaging variables. This automation
      facilitates integration with clinical variables derived by machine learning to
      predict patient outcome or diagnosis. In this review, we describe new imaging
      protocols made possible by the new hardware developments. We also discuss several
      novel software approaches for the quantification and interpretation of myocardial
      perfusion SPECT scans.

PMID- 29034067
TI  - Multiple- vs Non- or Single-Imputation based Fuzzy Clustering for Incomplete
      Longitudinal Behavioral Intervention Data.
AB  - Disentangling patients' behavioral variations is a critical step for better
      understanding an intervention's effects on individual outcomes. Missing data
      commonly exist in longitudinal behavioral intervention studies. Multiple
      imputation (MI) has been well studied for missing data analyses in the
      statistical field, however, has not yet been scrutinized for clustering or
      unsupervised learning, which are important techniques for explaining the
      heterogeneity of treatment effects. Built upon previous work on MI fuzzy
      clustering, this paper theoretically, empirically and numerically demonstrate how
      MI-based approach can reduce the uncertainty of clustering accuracy in comparison
      to non-and single-imputation based clustering approach. This paper advances our
      understanding of the utility and strength of multiple-imputation (MI) based fuzzy
      clustering approach to processing incomplete longitudinal behavioral intervention
      data.

PMID- 29034069
TI  - Scaffold hopping via ANCHOR.QUERY: beta-lactams as potent p53-MDM2 antagonists?.
AB  - Using the pharmacophore-based virtual screening platform ANCHOR.QUERY, we morphed
      our recently described Ugi-4CR scaffold towards a beta-lactam scaffold with
      potent p53-MDM2 antagonizing activities. 2D-HSQC and FP measurements confirm
      potent MDM2 binding. Molecular modeling studies are used to understand the
      observed SAR in the beta-lactam series.

PMID- 29034064
TI  - Personalized Therapy Against Preeclampsia by Replenishing Placental Protein 13
      (PP13) Targeted to Patients With Impaired PP13 Molecule or Function.
AB  - Hypertensive disorders affect about one third of all people aged 20 and above,
      and are treated with anti-hypertensive drugs. Preeclampsia (PE) is one form of
      such disorders that only develops during pregnancy. It affects ten million
      pregnant women globally and additionally causes fetal loss and major newborn
      disabilities. The syndrome's origin is multifactorial, and anti-hypertensive
      drugs are ineffective in treating it. Biomarkers are helpful for predict its
      development. Generic drugs, such as low dose aspirin, were proven effective in
      preventing preterm PE. However, it does not cure the majority of cases and many
      studies are underway for fighting PE with extended use of additional generic
      drugs, or through new drug development programs. This review focuses on placental
      protein 13 (PP13). This protein is only expressed in the placenta. Impaired PP13
      DNA structure and/or its reduced mRNA expression leads to lower blood PP13 level
      that predict a higher risk of developing PE. Two polymorphic PP13 variants have
      been identified: (1) The promoter PP13 variant with an "A/A" genotype in the -98
      position (versus "A/C" or "C/C"). Having the "A/A" genotype is coupled to lower
      PP13 expression, mainly during placental syncytiotrophoblast differentiation and,
      if associated with obesity and history of previous preeclampsia, it accurately
      predicts higher risk for developing the disorder. (2) A thymidine deletion at
      position 221 causes a frame shift in the open reading frame, and the formation of
      an early stop codon resulting in the formation of DelT221, a truncated variant of
      PP13. In pregnant rodents, both short- and long- term replenishment of PP13
      causes reversible hypotension and vasodilation of uterine vessels. Long-term
      exposure is also accompanied by the development of larger placentas and newborns.
      Also, only w/t PP13 is capable of inducing leukocyte apoptosis, providing
      maternal immune tolerance to pregnancy. Based on published data, we propose a
      targeted PP13 therapy to fight PE, and consider the design and conduct of animal
      studies to explore this hypothesis. Accordingly, a new targeted therapy can be
      implemented in humans combining prediction and prevention.

PMID- 29034070
TI  - Spontaneous resolution of symptomatic lumbar synovial cyst.
AB  - Lumbar synovial cyst arises from the facet joint and can lead to back pain,
      radiculopathy, neurogenic claudication or even cauda equina syndrome. Although
      most surgeons would consider surgery to be the treatment of choice, the natural
      history of the disease process remains unknown and uncertainty still exists
      regarding optimal management of this controversial entity. We illustrate a case
      of large L5/S1 synovial cyst for which surgery was initially planned. However, it
      resolved spontaneously without any treatment. We also provide a brief literature
      review regarding conservative, surgical and minimally invasive management of
      symptomatic lumbar synovial cyst with special reference to patient outcome.

PMID- 29034068
TI  - Clinical phenotype of ASD-associated DYRK1A haploinsufficiency.
AB  - BACKGROUND: DYRK1A is a gene recurrently disrupted in 0.1-0.5% of the ASD
      population. A growing number of case reports with DYRK1A haploinsufficiency
      exhibit common phenotypic features including microcephaly, intellectual
      disability, speech delay, and facial dysmorphisms. METHODS: Phenotypic
      information from previously published DYRK1A cases (n = 51) and participants in
      an ongoing study at the University of Washington (UW, n = 10) were compiled.
      Frequencies of recurrent phenotypic features in this population were compared to
      features observed in a large sample with idiopathic ASD from the Simons Simplex
      Collection (n = 1981). UW DYRK1A cases were further characterized quantitatively
      and compared to a randomly subsampled set of idiopathic ASD cases matched on age
      and gender (n = 10) and to cases with an ASD-associated disruptive mutation to
      CHD8 (n = 12). Contribution of familial genetic background to clinical
      heterogeneity was assessed by comparing head circumference, IQ, and ASD-related
      symptoms of UW DYRK1A cases to their unaffected parents. RESULTS: DYRK1A
      haploinsufficiency results in a common phenotypic profile including intellectual
      disability, speech and motor difficulties, microcephaly, feeding difficulties,
      and vision abnormalities. Eighty-nine percent of DYRK1A cases ascertained for ASD
      presented with a constellation of five or more of these symptoms. When compared
      quantitatively, DYRK1A cases presented with significantly lower IQ and adaptive
      functioning compared to idiopathic cases and significantly smaller head size
      compared to both idiopathic and CHD8 cases. Phenotypic variability in parental
      head circumference, IQ, and ASD-related symptoms corresponded to observed
      variability in affected child phenotype. CONCLUSIONS: Results confirm a core
      clinical phenotype for DYRK1A disruptions, with a combination of features that is
      distinct from idiopathic ASD. Cases with DYRK1A mutations are also
      distinguishable from disruptive mutations to CHD8 by head size. Measurable,
      quantitative characterization of DYRK1A haploinsufficiency illuminates clinical
      variability, which may be, in part, due to familial genetic background.

PMID- 25210619
TI  - Sub-strains of Drosophila Canton-S differ markedly in their locomotor behavior.
AB  - We collected five sub-strains of the standard laboratory wild-type
      Drosophilamelanogaster Canton Special (CS) and analyzed their walking behavior in
      Buridan's paradigm using the CeTrAn software. According to twelve different
      aspects of their behavior, the sub-strains fit into three groups. The group
      separation appeared not to be correlated with the origin of the stocks. We
      conclude that founder effects but not laboratory selection likely influenced the
      gene pool of the sub-strains. The flies' stripe fixation was the parameter that
      varied most. Our results suggest that differences in the genome of laboratory
      stocks can render comparisons between nominally identical wild-type stocks
      meaningless. A single source for control strains may settle this problem.

PMID- 29034071
TI  - Apigenin in cancer therapy: anti-cancer effects and mechanisms of action.
AB  - Apigenin is a common dietary flavonoid that is abundantly present in many fruits,
      vegetables and Chinese medicinal herbs and serves multiple physiological
      functions, such as strong anti-inflammatory, antioxidant, antibacterial and
      antiviral activities and blood pressure reduction. Therefore, apigenin has been
      used as a traditional medicine for centuries. Recently, apigenin has been widely
      investigated for its anti-cancer activities and low toxicity. Apigenin was
      reported to suppress various human cancers in vitro and in vivo by multiple
      biological effects, such as triggering cell apoptosis and autophagy, inducing
      cell cycle arrest, suppressing cell migration and invasion, and stimulating an
      immune response. In this review, we focus on the most recent advances in the anti
      cancer effects of apigenin and their underlying mechanisms, and we summarize the
      signaling pathways modulated by apigenin, including the PI3K/AKT, MAPK/ERK,
      JAK/STAT, NF-kappaB and Wnt/beta-catenin pathways. We also discuss combinatorial
      strategies to enhance the anti-cancer effect of apigenin on various cancers and
      its use as an adjuvant chemotherapeutic agent to overcome cancer drug resistance
      or to alleviate other adverse effects of chemotherapy. The functions of apigenin
      against cancer stem cells are also summarized and discussed. These data
      demonstrate that apigenin is a promising reagent for cancer therapy. Apigenin
      appears to have the potential to be developed either as a dietary supplement or
      as an adjuvant chemotherapeutic agent for cancer therapy.

PMID- 29034075
TI  - Structural brain abnormalities in 12 persons with aniridia.
AB  - Background: Aniridia is a disorder predominately caused by heterozygous loss-of
      function mutations of the PAX6 gene, which is a transcriptional regulator
      necessary for normal eye and brain development.  The ocular abnormalities of
      aniridia have been well characterized, but mounting evidence has implicated brain
      related phenotypes as a prominent feature of this disorder as well. 
      Investigations using neuroimaging in aniridia patients have shown reductions in
      discrete brain structures and changes in global grey and white matter.  However,
      limited sample sizes and substantive heterogeneity of structural phenotypes in
      the brain remain a challenge.  Methods: Here, we examined brain structure in a
      new population sample in an effort to add to the collective understanding of
      anatomical abnormalities in aniridia.  The current study used 3T magnetic
      resonance imaging to acquire high-resolution structural data in 12 persons with
      aniridia and 12 healthy demographically matched comparison subjects.  Results: We
      examined five major structures: the anterior commissure, the posterior
      commissure, the pineal gland, the corpus callosum, and the optic chiasm.  The
      most consistent reductions were found in the anterior commissure and the pineal
      gland; however, abnormalities in all of other structures examined were present in
      at least one individual.  Conclusions: Our results indicate that the anatomical
      abnormalities in aniridia are variable and largely individual-specific.  These
      findings suggest that future studies investigate this heterogeneity further, and
      that normal population variation should be considered when evaluating structural
      abnormalities.

PMID- 29034073
TI  - Unmet goals in the treatment of Acute Myocardial Infarction: Review.
AB  - Reperfusion therapy decreases myocardium damage during an acute coronary event
      and consequently mortality. However, there are unmet needs in the treatment of
      acute myocardial infarction, consequently mortality and heart failure continue to
      occur in about 10% and 20% of cases, respectively. Different strategies could
      improve reperfusion. These strategies, like generation of warning sign
      recognition and being initially assisted and transferred by an emergency service,
      could reduce the time to reperfusion. If the first electrocardiogram is performed
      en route, it can be transmitted and interpreted in a timely manner by a
      specialist at the receiving center, bypassing community hospitals without
      percutaneous coronary intervention capabilities. To administer thrombolytic
      therapy during transport to the catheterization laboratory could reduce time to
      reperfusion in cases with expected prolonged transport time to a percutaneous
      coronary intervention center or to a center without primary percutaneous coronary
      intervention capabilities with additional expected delay, known as pharmaco
      invasive strategy. Myocardial reperfusion is known to produce damage and cell
      death, which defines the reperfusion injury. Lack of resolution of ST segment is
      used as a marker of reperfusion failure. In patients without ST segment
      resolution, mortality triples. It is important to note that, until recently,
      reperfusion injury and no-reflow were interpreted as a single entity and we
      should differentiate them as different entities; whereas no-reflow is the failure
      to obtain tissue flow, reperfusion injury is actually the damage produced by
      achieving flow. Therefore, treatment of no-reflow is obtained by tissue flow,
      whereas in reperfusion injury the treatment objective is protection of
      susceptible myocardium from reperfusion injury. Numerous trials for the treatment
      of reperfusion injury have been unsuccessful. Newer hypotheses such as "
      controlled reperfusion", in which the interventional cardiologist assumes not
      only the treatment of the culprit vessel but also the way to reperfuse the
      myocardium at risk, could reduce reperfusion injury.

PMID- 29034074
TI  - Recent advances in managing chronic prostatitis/chronic pelvic pain syndrome.
AB  - Chronic prostatitis/chronic pelvic pain syndrome is a common disorder seen in men
      under the age of 50 and has a considerable negative impact on quality of life; it
      is a complex and difficult condition to treat, owing to its wide symptomatology.
      In order to effectively treat this condition, the UPOINT system was developed: it
      allows clinical profiling of a patient's symptoms into six broad categories
      (urinary symptoms, psychological dysfunction, organ-specific symptoms, infectious
      causes, neurologic dysfunction, and tenderness of the pelvic floor muscles) to
      allow individualized and multimodal therapy. In this review, we present the most
      recent advancements in the treatment of chronic prostatitis/chronic pelvic pain
      syndrome from the past few years.

PMID- 29034076
TI  - Accessibility to health services among migrant workers in the Northeast of
      Thailand.
AB  - Background. There is an increasing trend of trans-border migration from
      neighboring countries to Thailand. According to human rights laws, everyone must
      have access to health services, even if they are from other nationalities. 
      However, a small minority of health personnel in Thailand discriminate against
      immigrant workers, as they are from a lower financial bracket. Methods. This
      cross-sectional study aims to determine the prevalence of accessibility to health
      services and factors associated with access to health services among migrant
      workers who work along the Northeast border of Thailand. A total of 621 legal
      migrant workers were randomly selected to respond to a structured questionnaire
      about the satisfaction of health services, using the 5As of health services:
      availability; accessibility; accommodation; affordability; acceptability. 
      Associations between independent variables and access to health services were
      analysed   using multiple logistic regression analysis. Results. The results
      indicated that the majority of these registered migrant workers were female
      (63.9%) with an average age of 29+/- 8.61 years old, and were married (54.3%).
      Most of the workers worked at restaurants (80%), whereas only 20% were in
      agricultural sectors. Only 14% (95% CI: 11-17%) of migrant workers had access to
      health services. The factors that were significantly associated with
      accessibility to health service experienced ill health during the past one year
      (OR = 2.48; 95%CI; 1.54-3.97; p-value<0.001) ; have been married (OR = 2.32; 95%
      CI: 1.40 - 3.90; p-value <0.001). Conclusions. Most of the migrant workers could
      not access health services. The ones who did access health services were married
      or ill.

PMID- 29034078
TI  - Recent advances in cancer surgery in older patients.
AB  - Age is the most important risk factor for the occurrence of cancer, and a
      declining mortality from heart disease and other non-cancer causes leaves an
      older population that is at high risk of developing cancer. Choosing the optimal
      treatment for older cancer patients may be a challenge. Firstly, older age and
      associated factors such as comorbidities, functional limitations, and cognitive
      impairment are risk factors for adverse effects of cancer treatment. Secondly,
      older patients are often excluded from clinical trials, and current clinical
      guidelines rarely address how to manage cancer in patients who have comorbidities
      or functional limitations. The importance of incorporating frailty assessment
      into the preoperative evaluation of older surgical patients has received
      increasing attention over the last 10 years. Furthermore, studies that include
      endpoints such as functional status, cognitive status, and quality of life beyond
      the standard endpoints, i.e. postoperative morbidity and mortality, are starting
      to emerge. This review looks at recent evidence regarding geriatric assessment
      and frailty in older surgical cancer patients and provides a summary of newer
      studies in colorectal, liver, pancreatic, and gynecological cancer and renal and
      central nervous system tumors.

PMID- 29034077
TI  - Marine archaea and archaeal viruses under global change.
AB  - Global change is altering oceanic temperature, salinity, pH, and oxygen
      concentration, directly and indirectly influencing marine microbial food web
      structure and function. As microbes represent >90% of the ocean's biomass and are
      major drivers of biogeochemical cycles, understanding their responses to such
      changes is fundamental for predicting the consequences of global change on
      ecosystem functioning. Recent findings indicate that marine archaea and archaeal
      viruses are active and relevant components of marine microbial assemblages, far
      more abundant and diverse than was previously thought. Further research is
      urgently needed to better understand the impacts of global change on virus
      archaea dynamics and how archaea and their viruses can interactively influence
      the ocean's feedbacks on global change.

PMID- 29034080
TI  - Professional medical writing support and the reporting quality of randomized
      controlled trial abstracts among high-impact general medical journals.
AB  - Background: In articles reporting randomized controlled trials, professional
      medical writing support is associated with increased adherence to Consolidated
      Standards of Reporting Trials (CONSORT). We set out to determine whether
      professional medical writing support was also associated with improved adherence
      to CONSORT for Abstracts. Methods: Using data from a previously published cross
      sectional study of 463 articles reporting randomized controlled trials published
      between 2011 and 2014 in five top medical journals, we determined the association
      between professional medical writing support and CONSORT for Abstracts items
      using a Wilcoxon rank-sum test. Results: The mean proportion of adherence to
      CONSORT for Abstracts items reported was similar with and without professional
      medical writing support (64.3% vs 66.5%, respectively; p=0.30). Professional
      medical writing support was associated with lower adherence to reporting study
      setting (relative risk [RR]; 0.40; 95% confidence interval [CI], 0.23-0.70), and
      higher adherence to disclosing harms/side effects (RR 2.04; 95% CI, 1.37-3.03)
      and funding source (RR 1.75; 95% CI, 1.18-2.60). Conclusions: Although
      professional medical writing support was not associated with increased overall
      adherence to CONSORT for Abstracts, important aspects were improved with
      professional medical writing support, including reporting of adverse events and
      funding source. This study identifies areas to consider for improvement.

PMID- 29034079
TI  - Adaptation in the visual cortex: a case for probing neuronal populations with
      natural stimuli.
AB  - The perception of, and neural responses to, sensory stimuli in the present are
      influenced by what has been observed in the past-a phenomenon known as
      adaptation. We focus on adaptation in visual cortical neurons as a paradigmatic
      example. We review recent work that represents two shifts in the way we study
      adaptation, namely (i) going beyond single neurons to study adaptation in
      populations of neurons and (ii) going beyond simple stimuli to study adaptation
      to natural stimuli. We suggest that efforts in these two directions, through a
      closer integration of experimental and modeling approaches, will enable a more
      complete understanding of cortical processing in natural environments.

PMID- 29034081
TI  - Renal impairment in stroke patients: A comparison between the haemorrhagic and
      ischemic variants.
AB  - Background: Renal impairment is regularly seen in hospitalized stroke patients,
      affecting the outcome of patients, as well as causing difficulties in their
      management. A prospective cohort study was conducted to assess the trend of renal
      function in hospitalized ischemic and haemorrhagic stroke patients. The incidence
      of renal impairment in these subgroups, the contributing factors and the need for
      renal replacement in renal impaired patients was evaluated. Methods: Alternate
      day renal function testing was performed in hospitalized stroke patients.
      Estimated glomerular filtration rate (e-GFR) was calculated and the trend of
      renal function in the two stroke subgroups (haemorrhagic and ischemic) was
      assessed, with renal impairment defined as e-GFR < 60mL/ minute per 1.73m 2.
      Results: Among 52 patients, 25 had haemorrhagic stroke (mean age 59.81 +/- 14.67)
      and 27 had ischemic stroke (mean age 56.12 +/- 13.08). The mean e-GFR (mL/minute
      per 1.732m 2) at admission in the haemorrhagic stroke subgroup was 64.79 +/-
      25.85 compared to 86.04 +/- 26.09 in the ischemic stroke subgroup (p=0.005).
      Sixteen out of 25 (64%) patients in the haemorrhagic stroke subgroup and 9 out of
      27 (33.3%) patients in the ischemic subgroup developed renal impairment (p=0.27).
      The location of the bleed (p=0.8), volume of hematoma (p=0.966) and surgical
      intervention (p=0.4) did not predispose the patients to renal impairment. One out
      of 16 patients with haemorrhagic stroke (who eventually died), and 2 out of 9
      patients with ischemic stroke required renal replacement. Conclusion: Renal
      impairment is commonly seen in stroke patients, more so in patients who suffered
      haemorrhagic strokes.  The impairment, however, is transient and rarely requires
      renal replacement therapy.

PMID- 29034082
TI  - Functional characterizations of rare UBA1 variants in X-linked Spinal Muscular
      Atrophy.
AB  - Background: X-linked spinal muscular atrophy (XL-SMA) results from mutations in
      the Ubiquitin-Like Modifier Activating Enzyme 1 ( UBA1). Previously, four novel
      closely clustered mutations have been shown to cause this fatal infantile
      disorder affecting only males. These mutations, three missense and one
      synonymous, all lie within Exon15 of the UBA1 gene, which contains the active
      adenylation domain (AAD). Methods: In this study, our group characterized the
      three known missense variants in vitro. Using a novel Uba1 assay and other
      methods, we investigated Uba1 adenylation, thioester, and transthioesterification
      reactions in vitro to determine possible biochemical effects of the missense
      variants. Results: Our data revealed that only one of the three XL-SMA missense
      variants impairs the Ubiquitin-adenylating ability of Uba1. Additionally, these
      missense variants retained Ubiquitin thioester bond formation and
      transthioesterification rates equal to that found in the wild type. Conclusions:
      Our results demonstrate a surprising shift from the likelihood of these XL-SMA
      mutations playing a damaging role in Uba1's enzymatic activity with Ubiquitin, to
      other roles such as altering UBA1 mRNA splicing via the disruption of splicing
      factor binding sites, similar to a mechanism in traditional SMA, or disrupting
      binding to other important in vivo binding partners.  These findings help to
      narrow the search for the areas of possible dysfunction in the Ubiquitin
      proteasome pathway that ultimately result in XL-SMA. Moreover, this investigation
      provides additional critical understanding of the mutations' biochemical
      mechanisms, vital for the development of future effective diagnostic assays and
      therapeutics.

PMID- 29034083
TI  - The effect of cognitive-behavioral counseling on anxiety in the mothers of
      infants in the NICU:  A randomized controlled trial.
AB  - Background: Pressures and tensions in everyone's life can cause a wide range of
      mental disorders such as anxiety. One of these tensions is the birth of a baby
      who requires special care, which can cause personal and social problems for the
      mother if no appropriate measures are taken to help them. The present study was
      conducted to determine the effect of cognitive-behavioral counseling on anxiety
      in the mothers of infants in the Neonatal Intensive Care Unit. Methods: This
      randomized controlled trial recruited 90 women presenting to Kowsar Hospital in
      Qazvin in 2016. They were enrolled by convenience sampling and randomly assigned
      to control and intervention groups. Eight sessions were held for each group. Beck
      Anxiety Inventory was filled by mothers at the beginning of intervention, at the
      end of the eighth session and three weeks after the intervention. The data was
      analyzed by generalized estimating equations (GEE) method. Results: According to
      the results, maternal anxiety showed no significant differences between the two
      groups before intervention (p = 0.408 and p = 0.881). Based on GEE test, the mean
      score of anxiety was significantly different in the two groups (p = 0.026)
      immediately and three weeks after the intervention in that it was lower in the
      intervention group. Friedman test results also confirmed the reducing trend of
      mean score of anxiety in the three stages (p = 0.000). Conclusions: Counseling
      has a positive effect on reducing the anxiety of mothers of children with special
      needs, therefore it can be used to improve their condition.

PMID- 29034084
TI  - Protein unfolding mechanisms and their effects on folding experiments.
AB  - In this review, I discuss the various methods researchers use to unfold proteins
      in the lab in order to understand protein folding both in vitro and in vivo. The
      four main techniques, chemical-, heat-, pressure- and force-denaturation, produce
      distinctly different unfolded conformational ensembles. Recent measurements have
      revealed different folding kinetics from different unfolding mechanisms. Thus,
      comparing these distinct unfolded ensembles sheds light on the underlying free
      energy landscape of folding.

PMID- 29034085
TI  - AMP-activated protein kinase - not just an energy sensor.
AB  - Orthologues of AMP-activated protein kinase (AMPK) occur in essentially all
      eukaryotes as heterotrimeric complexes comprising catalytic alpha subunits and
      regulatory beta and gamma subunits. The canonical role of AMPK is as an energy
      sensor, monitoring levels of the nucleotides AMP, ADP, and ATP that bind
      competitively to the gamma subunit. Once activated, AMPK acts to restore energy
      homeostasis by switching on alternate ATP-generating catabolic pathways while
      switching off ATP-consuming anabolic pathways. However, its ancestral role in
      unicellular eukaryotes may have been in sensing of glucose rather than energy. In
      this article, we discuss a few interesting recent developments in the AMPK field.
      Firstly, we review recent findings on the canonical pathway by which AMPK is
      regulated by adenine nucleotides. Secondly, AMPK is now known to be activated in
      mammalian cells by glucose starvation by a mechanism that occurs in the absence
      of changes in adenine nucleotides, involving the formation of complexes with Axin
      and LKB1 on the surface of the lysosome. Thirdly, in addition to containing the
      nucleotide-binding sites on the gamma subunits, AMPK heterotrimers contain a site
      for binding of allosteric activators termed the allosteric drug and metabolite
      (ADaM) site. A large number of synthetic activators, some of which show promise
      as hypoglycaemic agents in pre-clinical studies, have now been shown to bind
      there. Fourthly, some kinase inhibitors paradoxically activate AMPK, including
      one (SU6656) that binds in the catalytic site. Finally, although downstream
      targets originally identified for AMPK were mainly concerned with metabolism,
      recently identified targets have roles in such diverse areas as mitochondrial
      fission, integrity of epithelial cell layers, and angiogenesis.

PMID- 29034086
TI  - How do you recognize and reconstitute a synaptic vesicle after fusion?
AB  - Synaptic vesicle recycling is essential for sustained and reliable
      neurotransmission. A key component of synaptic vesicle recycling is the synaptic
      vesicle biogenesis process that is observed in synapses and that maintains the
      molecular identity of synaptic vesicles. However, the mechanisms by which
      synaptic vesicles are retrieved and reconstituted after fusion remain unclear.
      The complex molecular composition of synaptic vesicles renders their rapid
      biogenesis a daunting task. Therefore, in this context, kiss-and-run type
      transient fusion of synaptic vesicles with the plasma membrane without loss of
      their membrane composition and molecular identity remains a viable hypothesis
      that can account for the fidelity of the synaptic vesicle cycle. In this article,
      we discuss the biological implications of this problem as well as its possible
      molecular solutions.

PMID- 29034087
TI  - Spironolactone in cardiovascular disease: an expanding universe?
AB  - Spironolactone has been marketed for over half a century as a 'potassium-sparing
      diuretic', used primarily in patients with ascites. With the realization that
      primary aldosteronism is the most common (5-13%) form of secondary hypertension,
      it has become widely used as a mineralocorticoid receptor antagonist. More
      recently, in the wake of the RALES trial, spironolactone in addition to standard
      therapy has been shown to be very beneficial in heart failure with a reduced
      ejection fraction. Despite the failure of the TOPCAT trial, spironolactone is
      being increasingly used in diastolic heart failure (i.e. with a preserved
      ejection fraction). The third currently accepted role for spironolactone is in
      hypertension resistant to three conventional antihypertensives including a
      diuretic, where it has been proven to be effective, in contra-distinction to
      renal artery denervation. Finally, brief consideration will be given to 'areas in
      waiting' - pulmonary hypertension/fibrosis, cancer - where spironolactone may
      play very useful roles.

PMID- 29034088
TI  - Emerging dilemmas in the diagnosis and management of gastroesophageal reflux
      disease.
AB  - Gastroesophageal reflux disease (GERD) is common, but less so than widely
      reported because of inconsistencies in definition. In clinical practice, the
      diagnosis is usually based on a symptom assessment without testing, and the
      extent of diagnostic testing pursued should be limited to that which guides
      management or which protects the patient from the risks of a potentially morbid
      treatment or an undetected early (or imminent) esophageal adenocarcinoma or which
      does both. When testing is pursued, upper gastrointestinal endoscopy is the most
      useful initial diagnostic test because it evaluates for the major potential
      morbidities (Barrett's, stricture, and cancer) associated with GERD and
      facilitates the identification of some alternative diagnostic possibilities such
      as eosinophilic esophagitis. However, endoscopy is insensitive for diagnosing
      GERD because most patients with GERD have non-erosive reflux disease, a
      persistent diagnostic dilemma. Although many studies have tried to objectify the
      diagnosis of GERD with improved technology, this is ultimately a pragmatic
      diagnosis based on response to proton pump inhibitor (PPI) therapy, and, in the
      end, response to PPI therapy becomes the major indication for continued PPI
      therapy. Conversely, in the absence of objective criteria for GERD and the
      absence of apparent clinical benefit, PPI therapy is not indicated and should be
      discontinued. PPIs are well tolerated and safe, but nothing is perfectly safe,
      and in the absence of measurable benefit, even a miniscule risk dominates the
      risk-benefit assessment.

PMID- 29034089
TI  - More than meets the IR: the expanding roles of variant Ionotropic Glutamate
      Receptors in sensing odor, taste, temperature and moisture.
AB  - The ionotropic receptors (IRs) are a branch of the ionotropic glutamate receptor
      family and serve as important mediators of sensory transduction in invertebrates.
      Recent work shows that, though initially studied as olfactory receptors, the IRs
      also mediate the detection of taste, temperature, and humidity. Here, we
      summarize recent insights into IR evolution and its potential ecological
      significance as well as recent advances in our understanding of how IRs
      contribute to diverse sensory modalities.

PMID- 29034091
TI  - Phenotypic and genotypic characterization of antibiotic resistance of methicillin
      resistant Staphylococcus aureus isolated from hospital food.
AB  - BACKGROUND: Pathogenic biotypes of the Methicillin-resistant Staphylococcus
      aureus (MRSA) strains are considered to be one of the major cause of food-borne
      diseases in hospitals. The present investigation was done to study the pattern of
      antibiotic resistance and prevalence of antibiotic resistance genes of different
      biotypes of the MRSA strains isolated from various types of hospital food
      samples. METHODS: Four-hundred and eighty-five raw and cooked hospital food
      samples were cultured and MRSA strains were identified using the oxacillin and
      cefoxitin disk diffusion tests and mecA-based PCR amplification. Isolated strains
      were subjected to biotyping and their antibiotic resistance patterns were
      analyzed using the disk diffusion and PCR methods. RESULTS: Prevalence of S.
      aureus and MRSA were 9.69 and 7.62%, respectively. Meat and chicken barbecues had
      the highest prevalence of MRSA. Prevalence of bovine, ovine, poultry and human
      based biotypes in the MRSA strains were 8.10, 8.10, 32.43 and 48.64%,
      respectively. All of the MRSA strains recovered from soup, salad and rice samples
      were related to human-based biotypes. MRSA strains harbored the highest
      prevalence of resistance against penicillin (100%), ceftaroline (100%),
      tetracycline (100%), erythromycin (89.18%) and trimethoprim-sulfamethoxazole
      (83.78%). TetK (72.97%), ermA (72.97%), msrA (64.86%) and aacA-D (62.16%) were
      the most commonly detected antibiotic resistance genes. CONCLUSIONS: Pattern of
      antibiotic resistance and also distribution of antibiotic resistance genes were
      related to the biotype of MRSA strains. Presence of multi-drug resistance and
      also simultaneous presence of several antibiotic resistance genes in some MRSA
      isolates showed an important public health issue Further researches are required
      to found additional epidemiological aspects of the MRSA strains in hospital food
      samples.

PMID- 29034090
TI  - Pre- to postoperative coagulation profile of 307 patients undergoing oesophageal
      resection with epidural blockade over a 10-year period in a single hospital:
      implications for the risk of spinal haematoma.
AB  - BACKGROUND: Epidural anaesthesia and analgesia are indicated for oesophageal
      surgery. A rare but serious complication is spinal haematoma, which can occur on
      insertion, manipulation or withdrawal of catheters. Evidence and guidelines are
      vague regarding which tests are appropriate and how to interpret their results.
      We aimed to describe how routine coagulation test results change during
      oesophagectomy's perioperative course. METHODS: Following ethical approval, we
      retrospectively identified patients who had undergone oesophagectomy between 2002
      and 2012. Blood test results and details of operations, haemorrhage and
      complications were recorded and analysed with Excel and R. A literature search
      was conducted using the PubMed terms 'epidural' AND 'coagulation' AND English
      language. Relevant articles published in 2000 and after were included. RESULTS:
      Three hundred and seven patients received a thoracic epidural infusion with
      bupivacaine and morphine while 51 received an intravenous morphine infusion.
      Tests taken preoperatively and before the planned withdrawal of the epidural
      catheter demonstrated increases in all three measures: aPTT (activated partial
      thromboplastin time), PT-INR (prothrombin international normalised ratio) and
      platelet count (Plc). Postoperative thrombocytopenia was almost non-existent
      while aPTT or PT-INR was elevated above the reference range in 129/307 patients:
      aPTT was elevated in 116/307 while PT-INR was elevated in 32/307. This is too
      small a sample to allow meaningful estimation of risk of spinal haematoma: it may
      be as high as 2.3%. The literature search returned 275 articles, of which 57 were
      relevant. Twenty-one concerned the natural history of postoperative coagulation;
      16, the incidence of and risk factors for spinal haematoma; and 5, evaluation of
      specific blood tests. Postoperative coagulation is characterised by
      thrombocytosis and transient moderately abnormal routine coagulation test
      results. Viscoelastic tests are not validated in the stable postoperative
      setting. CONCLUSIONS: Screening for coagulopathy before removal of epidural
      catheters is of unclear benefit since elevated aPTT and PT-INR are usual and may
      not indicate hypocoagulation. A thorough clinical assessment is important. We
      nevertheless recommend caution when being presented with elevated routine tests
      of coagulation before withdrawing an epidural catheter: viscoelastic haemostatic
      tests may have a role in testing before withdrawal of epidural catheters but they
      are so far not validated. Future research should include advanced coagulation
      analysis as soon as a patient is unfortunate enough to have a spinal haematoma.

PMID- 29034092
TI  - Choosing the uterine preservation surgery for placental polyp determined by blood
      flow evaluation: A retrospective cohort study.
AB  - BACKGROUND: A placental polyp is an intrauterine polypoid mass or pedunculated
      mass occurring from residual trophoblastic tissue following abortion, cesarean
      section or vaginal delivery. Recently uterine preservation surgery represented by
      transcervical resection (TCR) has been performed for placental polyps. However
      TCR without intravascular intervention, including uterine artery embolization
      (UAE) may cause profound bleeding which necessitate emergency laparotomy.
      METHODS: Seventeen cases of placental polyp were retrospectively examined. We
      divided cases into two groups: strong vascularity group (n = 13) and weak
      vascularity group (n = 4). Mass extraction of polyp by TCR was conducted in 16
      cases, 6 case without UAE and 10 cases with UAE. RESULTS: As for the weak
      vascularity group, one case was naturally resolved while planning surgery and 3
      cases were treated with TCR without UAE without major intra- and/or postoperative
      bleeding. On the other hand in the strong vascularity group, 2 out of 3 cases of
      TCR without UAE resulted in major bleeding during and after the surgery, both
      needed transfusion and one needing postoperative UAE. Ten cases of strong
      vascularity group, TCR with UAE were performed and all of them were accomplished
      without major bleeding. TCR without UAE was safely performed in cases where there
      was absent or mild to moderate blood flow. CONCLUSIONS: Our report suggests that
      adding UAE might be safer to treat placental polyps that have strong vascularity.

PMID- 29034093
TI  - Sentinel surveillance of influenza-like illness in the Central African Republic,
      2010-2015.
AB  - BACKGROUND: Influenza-like illness (ILI) is an important public health problem
      worldwide. In the Central African Republic, acute infectious diseases are the
      commonest reason for consultation. The Institut Pasteur of Bangui set up a
      surveillance network in 2008 to monitor the circulation of influenza viruses. We
      report the results of use of this surveillance system during the period 2010
      2015. METHODS: The first surveillance centre covered Bangui, the capital of the
      country, and neighbouring areas and epidemiological data on syndromes similar to
      ILI. Throat and nasopharyngeal swab samples are transmitted weekly to the
      Institut Pasteur of Bangui, where real-time and multiplex reverse transcription
      polymerase chain reaction are used to detect and subtype influenza A (H1N1 and
      H3N2) and B viruses. The demographic characteristics of all patients and of
      positive cases according to age and the seasonal patterns of influenza virus
      circulation were analysed. RESULTS: Between January 2010 and December 2015, 5385
      throat swabs were collected; 454 (8.4%) of the samples were positive. Of these,
      450 yielded at least one influenza virus and four showed co-infections. Children
      under the age of 5 years were the most frequently infected (257/450, 57.1%), with
      irregular peaks of ILI. Influenza B predominated (56.2%; n = 201), with 39.0%
      H3N2 and 16.7%H1N1pdm09. Influenza viruses were detected mainly in the rainy
      season (July-December). CONCLUSION: The sentinel surveillance site is yielding
      important information about the seasonality and age pattern of circulating
      influenza virus. Nationwide distribution of sentinel sites is warranted.

PMID- 29034094
TI  - Antibiotic therapy, supportive treatment and management of immunomodulation
      inflammation response in community acquired pneumonia: review of recommendations.
AB  - Community-acquired pneumonia is a common and serious disease, with high rates of
      morbidity and mortality. Management and treatment of community-acquired pneumonia
      are described in three main documents: the 2007 American Thoracic Society
      guidelines, the 2011 European Respiratory Society guidelines, and the 2009
      British Thoracic Society guidelines, updated by the NICE in 2015. Despite the
      validity of current guidelines in improving prognosis and management of patients
      with community-acquired pneumonia, not all recommendations have high levels of
      evidence and there are still some controversial issues. In particular, there are
      some areas of low evidence such as the efficacy of an antibiotic molecule or
      scheme in patients with same risk factors; duration of antibiotic treatment,
      supportive therapy for acute respiratory failure and immunomodulation molecules.
      This review will summarize the main recommendations with high level of evidence
      and discuss the recommendations with lower evidence, analyzing the studies
      published after the guidelines' release.

PMID- 29034095
TI  - Current and emerging brain applications of MR-guided focused ultrasound.
AB  - MRI guided focused ultrasound is an emerging technique that uses acoustic energy
      to noninvasively treat intracranial disorders. At high frequencies, it can be
      used to raise tissue temperatures and ablate discrete brain targets with sub
      millimeter accuracy. This application is currently under investigation for a
      broad range of clinical applications, including brain tumors, movement disorders,
      and psychiatric conditions. At low frequencies MRI guided focused ultrasound can
      be used to modulate neuronal activity and in conjunction with injected
      microbubbles, can open the blood-brain barrier to enhance the delivery of
      therapeutic compounds. The last decade has seen dramatic advances in the science
      of MRI guided focused ultrasound, helping elucidate both its mechanisms and
      potential in pre-clinical models, and its translational promise across myriad
      clinical applications. This review provides an update of current and emerging MRI
      guided focused ultrasound applications for intracranial disorders and describes
      future directions and challenges for the field.

PMID- 29034096
TI  - Evaluating the impact of Brexit on the pharmaceutical industry.
AB  - INTRODUCTION: The UK Pharmaceutical Industry is arguably one of the most
      important industries to consider in the negotiations following the Brexit vote.
      Providing tens of thousands of jobs and billions in tax revenue and research
      investment, the importance of this industry cannot be understated. At stake is
      the global leadership in the sector, which produces some of the field's most
      influential basic science and translation work. However, interruptions and losses
      may occur at multiple levels, affecting patients, researchers, universities,
      companies and government. GOALS: By understanding the current state of
      pharmaceutical sector, the potential effect of leaving the European Union (EU) on
      this successful industry can be better understood. This paper aims to address the
      priorities for negotiations by collating the analyses of professionals in the
      field, leading companies and non-EU member states. RESEARCH METHODS: A government
      healthcare policy advisor and Chief Science Officer (CSO) for a major
      pharmaceutical firm were consulted to scope the paper. In these discussions, five
      key areas were identified: contribution, legislative processes, regulatory
      processes, research and outcomes, commercial risk. Multiple search engines were
      utilised for selecting relevant material, predominantly PubMed and Google
      Scholar. To supplement this information, Government documents were located using
      the "GOV.UK" publications tool, and interviews and commentaries were found
      through the Google News search function. CONCLUSION: With thorough investigation
      of the literature, we propose four foundations in the advancement of
      negotiations. These prioritise: negotiation of 'associated country' status,
      bilaterally favourable trade agreements, minimal interruption to regulatory
      bodies and special protection for the movement of workforce in the life sciences
      industry.

PMID- 29034097
TI  - The association between cadmium and lead exposure and blood pressure among
      workers of a smelting industry: a cross-sectional study.
AB  - BACKGROUND: Lead and cadmium are harmful heavy metals that are used for a variety
      of occupational purposes. Considering their potentially hazardous effects on
      health, studies on the association between exposure to these two heavy metals and
      health disorders have been actively conducted. This study aimed to determine the
      association between blood lead and cadmium levels and blood pressure in workers
      exposed to lead and cadmium in a smelter. METHODS: Nine hundred and sixty-three
      male workers who worked in a smelter, and underwent medical examinations at the
      Ulsan University Hospital between January 1 and December 31, 2014, were selected
      as participants. Among them, 310 subjects whose data on height, weight, blood
      pressure, fasting blood glucose, lipid profile, and blood lead and cadmium levels
      were available and who answered the questionnaire were selected as the final
      participants. We investigated the drinking habit, smoking status, exercise
      adequacy, and family history of hypertension of these workers using formal
      questionnaires. A statistical analysis was conducted using Student's t-test,
      analysis of variance, and linear or logistic regression. RESULTS: The association
      between blood lead and cadmium levels and blood pressure was analyzed through
      statistical adjustment of the risk factors of hypertension. Results showed an
      association between blood cadmium level and blood pressure elevation. However,
      blood lead level was found to be not correlated with blood pressure elevation.
      CONCLUSIONS: This study shows the association between blood cadmium level and
      systolic blood pressure (SBP) and diastolic blood pressure (DBP) elevation. TRIAL
      REGISTRATION: IRB No. 2017-03-037. Retrospectively Registered 30 March 2017.

PMID- 29034098
TI  - Relative deprivation and individual well-being: Low status and a feeling of
      relative deprivation are detrimental to health and happiness.
AB  - People who are unable to maintain the same standard of living as others around
      them experience a sense of relative deprivation that has been shown to reduce
      feelings of well-being. Relative deprivation reflects conditions of worsening
      relative poverty despite striking reductions in absolute poverty. The effects of
      relative deprivation explain why average happiness has been stagnant over time
      despite sharp rises in income. Consumption taxes on status-seeking spending,
      along with official and traditional sanctions on excess consumption and
      redistributive policies may lessen the negative impact of relative deprivation on
      well-being.

PMID- 29034099
TI  - Lumbopelvic rhythm during trunk motion in the sagittal plane: A review of the
      kinematic measurement methods and characterization approaches.
AB  - Lumbopelvic rhythm during trunk forward bending and backward return has been
      widely investigated to have a better understanding of the pattern of trunk
      motion, as used in research on low back disorders. Considerable differences in
      the methods used to measure, and approaches used to characterize the lumbopelvic
      rhythm hinder the integration of findings of those studies for further research
      in the future. Thus, the purpose of this review was to summarize the methods for
      kinematic measurement as well as their characterization approaches for the
      lumbopelvic rhythm. PUBMED and CINAHL databases were searched for relevant
      studies. Several types of instruments were found to be used in the reviewed
      studies, mostly using markers or sensors, which were placed on different parts of
      spine, with different definitions to measure the lumbar and pelvic motion. Also,
      various characterization approaches were found to be used, of which some related
      to the magnitude, while the others to the timing aspects of lumbopelvic rhythm.
      Such a characterization was either qualitative or quantitative. In addition, the
      specified characterization approaches were applied on a sample of trunk
      kinematics data from our lab to demonstrate differences in the outcomes of these
      approaches.

PMID- 29034100
TI  - Prevalence of mental health conditions and relationship with general health in a
      whole-country population of people with intellectual disabilities compared with
      the general population.
AB  - BACKGROUND: There are no previous whole-country studies on mental health and
      relationships with general health in intellectual disability populations; study
      results vary. AIMS: To determine the prevalence of mental health conditions and
      relationships with general health in a total population with and without
      intellectual disabilities. METHOD: Ninety-four per cent completed Scotland's
      Census 2011. Data on intellectual disabilities, mental health and general health
      were extracted, and the association between them was investigated. RESULTS: A
      total of 26 349/5 295 403 (0.5%) had intellectual disabilities. In total, 12.8%
      children, 23.4% adults and 27.2% older adults had mental health conditions
      compared with 0.3, 5.3 and 4.5% of the general population. Intellectual
      disabilities predicted mental health conditions; odds ratio (OR)=7.1 (95% CI 6.8
      7.3). General health was substantially poorer and associated with mental health
      conditions; fair health OR=1.8 (95% CI 1.7-1.9), bad/very bad health OR=4.2 (95%
      CI 3.9-4.6). CONCLUSIONS: These large-scale, whole-country study findings are
      important, given the previously stated lack of confidence in comparative
      prevalence results, and the need to plan services accordingly. DECLARATION OF
      INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2017.
      This is an open access article distributed under the terms of the Creative
      Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 29034101
TI  - Lamotrigine-induced sexual dysfunction and non-adherence: case analysis with
      literature review.
AB  - BACKGROUND: Optimal anti-epileptic drug (AED) treatment maximises therapeutic
      response and minimises adverse effects (AEs). Key to therapeutic AED treatment is
      adherence. Non-adherence is often related to severity of AEs. Frequently,
      patients do not spontaneously report, and clinicians do not specifically query,
      critical AEs that lead to non-adherence, including sexual dysfunction. Sexual
      dysfunction prevalence in patients with epilepsy ranges from 40 to 70%, often
      related to AEDs, epilepsy or mood states. This case reports lamotrigine-induced
      sexual dysfunction leading to periodic non-adherence. AIMS: To report lamotrigine
      induced sexual dysfunction leading to periodic lamotrigine non-adherence in the
      context of multiple comorbidities and concurrent antidepressant and
      antihypertensive pharmacotherapy. METHOD: Case analysis with PubMed literature
      review. RESULTS: A 56-year-old male patient with major depression, panic disorder
      without agoraphobia and post-traumatic stress disorder was well-controlled with
      escitalopram 20 mg bid, mirtazapine 22.5 mg qhs and alprazolam 1 mg tid prn.
      Comorbid conditions included complex partial seizures, psychogenic non-epileptic
      seizures (PNES), hypertension, gastroesophageal reflux disease and hydrocephalus
      with patent ventriculoperitoneal shunt that were effectively treated with
      lamotrigine 100 mg tid, enalapril 20 mg qam and lansoprazole 30 mg qam. He
      acknowledged non-adherence with lamotrigine secondary to sexual dysfunction. With
      lamotrigine 300 mg total daily dose, he described no libido with
      impotence/anejaculation/anorgasmia. When off lamotrigine for 48 h, he described
      becoming libidinous with decreased erectile dysfunction but persistent
      anejaculation/anorgasmia. When off lamotrigine for 72 h to maximise sexual
      functioning, he developed auras. Family confirmed patient's consistent monthly
      non-adherence for 2-3 days during the past year. CONCLUSIONS: Sexual dysfunction
      is a key AE leading to AED non-adherence. This case describes dose-dependent
      lamotrigine-induced sexual dysfunction with episodic non-adherence for 12 months.
      Patient/clinician education regarding AED-induced sexual dysfunction is warranted
      as are routine sexual histories to ensure adherence. DECLARATION OF INTEREST: No
      financial interests. K.R.K. is Editor of BJPsych Open; he took no part in the
      peer-review of this work. COPYRIGHT AND USAGE: (c) The Royal College of
      Psychiatrists 2017. This is an open access article distributed under the terms of
      the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

PMID- 29034104
TI  - Fibroblasts: The Unknown Sentinels Eliciting Immune Responses Against
      Microorganisms.
AB  - Fibroblasts are present in all tissues but predominantly in connective tissues.
      Some of their functions include contractility, locomotion, collagen and elastin
      fiber production, and the regulation and degradation of the extracellular matrix.
      Also, fibroblasts act as sentinels to produce inflammatory mediators in response
      to several microorganisms. There is evidence that fibroblasts can synthesize toll
      like receptors (TLRs), antimicrobial peptides, proinflammatory cytokines,
      chemokines, and growth factors, which are important molecules involved in innate
      immune response against microorganisms. Fibroblasts can express TLRs (TLR-1 to
      TLR-10) to sense microbial components or microorganisms. They can synthesize
      antimicrobial peptides, such as LL-37, defensins hBD-1, and hBD-2, molecules that
      perform antimicrobial activity. Also, they can produce proinflammatory cytokines,
      such as TNFalpha, INFgamma, IL-6, IL-12p70, and IL-10; other chemokines, such as
      CCL1, CCL2, CCL5, CXCL1, CXCL8, CXCL10, and CX3CL1; and the growth factors
      granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony
      stimulating factor (G-CSF) to induce and recruit inflammatory cells. According to
      their immunological attributes, we can conclude that fibroblasts are sentinel
      cells that recognize pathogens, induce the recruitment of inflammatory cells via
      cytokines and growth factors, and release antimicrobial peptides, complying with
      the characteristics of real sentinels.

PMID- 29034102
TI  - New directions in hypnosis research: strategies for advancing the cognitive and
      clinical neuroscience of hypnosis.
AB  - This article summarizes key advances in hypnosis research during the past two
      decades, including (i) clinical research supporting the efficacy of hypnosis for
      managing a number of clinical symptoms and conditions, (ii) research supporting
      the role of various divisions in the anterior cingulate and prefrontal cortices
      in hypnotic responding, and (iii) an emerging finding that high hypnotic
      suggestibility is associated with atypical brain connectivity profiles. Key
      recommendations for a research agenda for the next decade include the
      recommendations that (i) laboratory hypnosis researchers should strongly consider
      how they assess hypnotic suggestibility in their studies, (ii) inclusion of study
      participants who score in the middle range of hypnotic suggestibility, and (iii)
      use of expanding research designs that more clearly delineate the roles of
      inductions and specific suggestions. Finally, we make two specific suggestions
      for helping to move the field forward including (i) the use of data sharing and
      (ii) redirecting resources away from contrasting state and nonstate positions
      toward studying (a) the efficacy of hypnotic treatments for clinical conditions
      influenced by central nervous system processes and (b) the neurophysiological
      underpinnings of hypnotic phenomena. As we learn more about the
      neurophysiological mechanisms underlying hypnosis and suggestion, we will
      strengthen our knowledge of both basic brain functions and a host of different
      psychological functions.

PMID- 29034105
TI  - Changes of the Intestinal Microbiome-Host Homeostasis in HIV-Infected Individuals
      - A Focus on the Bacterial Gut Microbiome.
AB  - Human immunodeficiency virus (HIV) infections cause severe CD4+ T cell depletion
      leading to chronic inflammation and immune activation, impaired barrier function,
      and microbial translocation. Even under effective antiretroviral therapy, these
      processes persist, leading to gut microbiome dysbiosis and disturbance of
      microbiome-host homeostasis. This systematic review aims at analyzing how gut
      microbiome and host immune system influence each other during HIV pathogenesis.
      An online search applying the PubMed database was conducted. The number of total
      results (n = 35) was narrowed down to 5 relevant studies focusing on the
      interaction between the host and gut microbiome, whereas strict exclusion
      criteria were applied, thereby assuring that no other comorbidities impacted
      study results. Our analyses revealed that gut microbiome diversity correlated
      positively with CD4+ T cell counts and negatively with microbial translocation
      markers. However, quantitative changes in bacterial richness did not consistently
      correlate with the numbers of metabolically active bacterial populations. Despite
      the reported increase in potentially pathogenic bacteria and, conversely,
      decrease in protective populations, the gut microbiota exhibited immune
      modulating qualities given that mucosal inflammatory sequelae were dampened by
      decreasing pro-inflammatory and accelerating anti-inflammatory cytokine
      responses. Future research is needed to further elucidate these findings, to gain
      a deeper insight into host-microbiota interactions and to develop novel
      therapeutic strategies.

PMID- 29034106
TI  - Epidemiology and Antibiotic Resistance Phenotypes of Diarrheagenic Escherichia
      Coli Responsible for Infantile Gastroenteritis in Ouagadougou, Burkina Faso.
AB  - The emergence and persistence of multidrug-resistant (MDR) diarrheagenic
      Escherichia coli (DEC) causing acute diarrhea is a major public health challenge
      in developing countries. The aim of this study was to evaluate the resistance
      phenotypes of DEC isolated from stool samples collected from children less than 5
      years of age with acute diarrhea living in Ouagadougou/Burkina Faso. From August
      2013 to October 2015, this study was carried out on 31 DEC strains of our study
      conducted in "Centre Medical avec Antenne Chirurgicale (CMA)" Paul VI and CMA of
      Schiphra. DEC were isolated and identified by standard microbiological methods
      and polymerase chain reaction (PCR) method was used to further characterize them.
      Antimicrobial susceptibility testing was done based on the disk diffusion method.
      DEC isolates were high resistant to tetracycline (83.9%), amoxicillin (77.4%),
      amoxicillin clavulanic acid (77.4%), piperacillin (64.5%), and colistin sulfate
      (61.3%). The most resistant phenotype represented was the extended spectrum beta
      lactamase (ESBL) phenotype (67.7%). Aminoglycosides were 100% active on
      enteroinvasive E. coli (EIEC) and enterohemorrhagic E. coli (EHEC). All the DEC
      isolates exhibited absolute (100%) sensitivity to ciprofloxacin. Monitoring and
      studying the resistance profile of DEC to antibiotics are necessary to guide
      probabilistic antibiotic therapy, especially in pediatric patients.

PMID- 29034103
TI  - Genomic insights into head and neck cancer.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer
      worldwide and is frequently impervious to curative treatment efforts. Similar to
      other cancers associated with prolonged exposure to carcinogens, HNSCCs often
      have a high burden of mutations, contributing to substantial inter- and intra
      tumor heterogeneity. The heterogeneity of this malignancy is further increased by
      the rising rate of human papillomavirus (HPV)-associated (HPV+) HNSCC, which
      defines an etiological subtype significantly different from the more common
      tobacco and alcohol associated HPV-negative (HPV-) HNSCC. Since 2011, application
      of large scale genome sequencing projects by The Cancer Genome Atlas (TCGA)
      network and other groups have established extensive datasets to characterize HPV-
      and HPV+ HNSCC, providing a foundation for advanced molecular diagnoses,
      identification of potential biomarkers, and therapeutic insights. Some genomic
      lesions are now appreciated as widely dispersed. For example, HPV- HNSCC
      characteristically inactivates the cell cycle suppressors TP53 (p53) and CDKN2A
      (p16), and often amplifies CCND1 (cyclin D), which phosphorylates RB1 to promote
      cell cycle progression from G1 to S. By contrast, HPV+ HNSCC expresses viral
      oncogenes E6 and E7, which inhibit TP53 and RB1, and activates the cell cycle
      regulator E2F1. Frequent activating mutations in PIK3CA and inactivating
      mutations in NOTCH1 are seen in both subtypes of HNSCC, emphasizing the
      importance of these pathways. Studies of large patient cohorts have also begun to
      identify less common genetic alterations, predominantly found in HPV- tumors,
      which suggest new mechanisms relevant to disease pathogenesis. Targets of these
      alterations including AJUBA and FAT1, both involved in the regulation of
      NOTCH/CTNNB1 signaling. Genes involved in oxidative stress, particularly CUL3,
      KEAP1 and NFE2L2, strongly associated with smoking, have also been identified,
      and are less well understood mechanistically. Application of sophisticated data
      mining approaches, integrating genomic information with profiles of tumor
      methylation and gene expression, have helped to further yield insights, and in
      some cases suggest additional approaches to stratify patients for clinical
      treatment. We here discuss some recent insights built on TCGA and other genomic
      foundations.

PMID- 29034107
TI  - High-Throughput Testing of Urogenital and Extragenital Specimens for Detection of
      Chlamydia Trachomatis and Neisseria Gonorrhoeae with Cobas(r) CT/NG.
AB  - We compared the analytical and clinical performance of cobas(r) CT/NG for use on
      the Cobas(r) 6800/8800 Systems with the Cobas(r) 4800 CT/NG Test from urogenital
      and extragenital specimens in over 12,000 specimens from both male and female
      subjects in Germany and the United States. The analytical sensitivity was <=40
      EB/ml for Chlamydia trachomatis (CT) and <=1 CFU/ml for Neisseria gonorrhoeae
      (NG). Using clinical specimens, the overall percent agreement with the Cobas(r)
      4800 CT/NG Test was >98.5%. Across urogenital specimens, there were 93 discrepant
      specimens; 76 (93.8%) of 81 CT discrepant specimens were 6800+/4800- and 10
      (83.3%) of 12 NG discrepant specimens were 6800+/4800-. Sequencing verified CT
      results for 45 (61.6%) of 73 samples positive by 6800 and 1 (20%) of 5 positive
      by 4800. Similarly, 7 (70.0%) of 10 NG samples positive by 6800 and 1 of 2
      positive by 4800 were confirmed by sequencing. Among discrepant extragenital
      specimens (all 6800+/4800-), 7 (50%) of 14 oropharyngeal and 23 (76.7%) of 30
      anorectal CT discordant samples were confirmed as CT positive by sequencing; all
      8 anorectal and 20 (90.9%) of 22 oropharyngeal NG discordant results were also
      confirmed as NG positive. In conclusion, Cobas(r) CT/NG for use on the Cobas(r)
      6800/8800 Systems provides high-throughput automated solutions for sexually
      transmitted infection (STI) screening programs.

PMID- 29034108
TI  - Intestinal Microbiota Changes in Mice Lacking Pituitary Adenylate Cyclase
      Activating Polypeptide (PACAP) - Bifidobacteria Make the Difference.
AB  - Pituitary adenylate cyclase activating polypetide (PACAP) constitutes a
      neuropeptide that is widely distributed in the host exerting essential
      cytoprotective properties, whereas PACAP-/- mice display increased susceptibility
      to distinct immunopathological conditions. The orchestrated interplay between the
      gut microbiota and the host is pivotal in immune homeostasis and resistance to
      disease. Potential pertubations of the intestinal microbiota in PACAP-/- mice,
      however, have not been addressed so far. For the first time, we performed a
      comprehensive survey of the intestinal microbiota composition in PACAP-/- and
      wildtype (WT) mice starting 2 weeks postpartum until 18 months of age applying
      quantitative culture-independent techniques. Fecal enterobacteria and enterococci
      were lower in PACAP-/- than WT mice aged 1 month and >=6 months, respectively.
      Whereas Mouse Intestinal Bacteroides were slightly higher in PACAP-/- versus WT
      mice aged 1 and 6 months, this later in life held true for Bacteroides/Prevotella
      spp. (>=12 months) and lactobacilli (>15 months of age). Strikingly, health
      beneficial bifidobacteria were virtually absent in the intestines of PACAP-/-
      mice, even when still breastfed. In conclusion, PACAP deficiency is accompanied
      by distinct changes in fecal microbiota composition with virtually absent
      bifidobacteria as a major hallmark that might be linked to increased
      susceptibility to disease.

PMID- 29034109
TI  - Multidrug-Resistant Pseudomonas Aeruginosa Induce Systemic Pro-Inflammatory
      Immune Responses in Colonized Mice.
AB  - The World Health Organization has rated multidrug-resistant (MDR) Pseudomonas
      aeruginosa as a critical threat to human health. In the present study, we
      performed a survey of intestinal colonization, and local and systemic immune
      responses following peroral association of secondary abiotic mice with either a
      clinical MDR P. aeruginosa or a commensal murine Escherichia coli isolate.
      Depletion of the intestinal microbiota following antibiotic treatment facilitated
      stable intestinal colonization of both P. aeruginosa and E. coli that were
      neither associated with relevant clinical nor histopathological sequelae. Either
      stable bacterial colonization, however, resulted in distinct innate and adaptive
      immune cell responses in the intestines, whereas a pronounced increase in
      macrophages and monocytes could be observed in the small as well as large
      intestines upon P. aeruginosa challenge only, which also applied to colonic T
      lymphocytes. In addition, TNF secretion was exclusively elevated in large
      intestines of P. aeruginosa-colonized mice. Strikingly, association of secondary
      abiotic mice with MDR P. aeruginosa, but not commensal E. coli, resulted in
      pronounced systemic pro-inflammatory responses, whereas anti-inflammatory
      responses were dampened. Hence, intestinal carriage of MDR P. aeruginosa as
      compared to a mere commensal Gram-negative strain in otherwise healthy
      individuals results in distinct local and systemic pro-inflammatory sequelae.

PMID- 29034110
TI  - Toll-Like Receptor-4 Dependent Inflammatory Responses Following Intestinal
      Colonization of Secondary Abiotic IL10-Deficient Mice with Multidrug-Resistant
      Pseudomonas Aeruginosa.
AB  - The rising incidences of infections with multidrug-resistant (MDR) Gram-negative
      bacteria including Pseudomonas aeruginosa (PA) have gained increasing attention
      in medicine, but also in the general public and global health politics. The
      mechanisms underlying opportunistic pathogen-host interactions are unclear,
      however. To address this, we challenged secondary abiotic IL10-/- mice deficient
      for Toll-like receptor-4 (TLR4-/- * IL10-/-), the main receptor of the Gram
      negative cell wall constituent lipopolysaccharide, with a clinical MDR PA
      isolate. Despite higher intestinal colonization densities, apoptotic colonic
      epithelial cell numbers were lower in TLR4-/- * IL10-/- mice as compared to IL10
      /- controls at day 14 postinfection (p.i.), whereas proliferating/regenerating
      cells had increased in the latter only. Furthermore, PA-colonized TLR4-/- * IL10
      /- mice displayed less distinct innate and adaptive immune cell responses in the
      colon as compared to IL10-/- counterparts that were accompanied by lower nitric
      oxide concentrations in mesenteric lymph nodes in the former at day 14 p.i.
      Conversely, splenic NO levels were higher in both naive and PA-colonized TLR4
      deficient IL10-/- mice versus IL10-/- controls. Remarkably, intestinal MDR PA was
      able to translocate to extra-intestinal including systemic compartments of TLR4-/
      * IL10-/- mice only. Hence, MDR PA-induced intestinal and systemic immune
      responses observed in secondary abiotic IL10-/- mice are TLR4-dependent.

PMID- 29034111
TI  - Molecular Characterization of Diarrheagenic Escherichia Coli in Children Less
      Than 5 Years of Age with Diarrhea in Ouagadougou, Burkina Faso.
AB  - Diarrheagenic Escherichia coli (DEC) is important bacteria of children's endemic
      and epidemic diarrhea worldwide. The aim of this study was to determine the
      prevalence of DEC isolated from stool samples collected from children with acute
      diarrhea living in Ouagadougou, Burkina Faso. From August 2013 to October 2015,
      stool samples were collected from 315 children under 5 years of age suffering
      from diarrhea in the "Centre Medical avec Antenne Chirurgicale (CMA)" Paul VI and
      the CMA of Schiphra. E. coli were isolated and identified by standard
      microbiological methods, and the 16-plex PCR method was used to further
      characterize them. Four hundred and nineteen (419) E. coli strains were
      characterized, of which 31 (7.4%) DEC pathotypes were identified and classified
      in five E. coli pathotypes: 15 enteroaggregative E. coli (EAEC) (48.4%), 8
      enteropathogenic E. coli (EPEC) (25.8%) with 4 typical EPEC and 4 atypical EPEC,
      4 enteroinvasive E. coli (EIEC) (12.9%), 3 enterohemorrhagic E. coli (EHEC)
      9.67%, and 1 enterotoxigenic E. coli (ETEC) 3.2%. The use of multiplex PCR as a
      routine in clinical laboratory for the detection of DEC would be a useful mean
      for a rapid management of an acute diarrhea in children.

PMID- 29034112
TI  - Lack of Association Between Cytomegalovirus Infection and Hypertensive Disorders
      in Pregnancy: A Case-Control Study in Durango, Mexico.
AB  - It is not clear whether infection with cytomegalovirus (CMV) is associated with
      hypertensive disorders in pregnant women. Through a case-control study design,
      146 women suffering from hypertensive disorders in pregnancy (cases) and 146 age
      matched normotensive pregnant women (controls) were examined for the presence of
      anti-CMV IgG and IgM antibodies with enzyme-linked immunoassays. IgM seropositive
      samples were further assayed by enzyme-linked fluorescent assay (ELFA). Anti-CMV
      IgG antibodies were found in 138 (94.5%) controls and in 136 (93.2%) cases (odds
      ratio [OR] = 0.78; 95% confidence interval [CI]: 0.30-2.05; P = 0.62). High (>18
      IU/ml) levels of anti-CMV IgG antibodies were found in 37.7% of the 138
      seropositive controls and in 34.6% of the 136 seropositive cases (OR = 0.87; 95%
      CI: 0.53-1.43; P = 0.59). Anti-CMV IgM antibodies were found in 1 (0.7%) of the
      controls but in none of the cases using ELFA (P = 1.0). Seropositivity to CMV was
      not associated with a previous preeclampsia and was similar among cases
      regardless their mean systolic and diastolic blood pressures, and mean arterial
      blood pressure. No serological evidence of an association between CMV infection
      and hypertensive disorders of pregnancy was found. Further research to elucidate
      the role of CMV in hypertensive disorders in pregnancy should be conducted.

PMID- 29034113
TI  - Low Neurotoxicity of ONX-0914 Supports the Idea of Specific Immunoproteasome
      Inhibition as a Side-Effect-Limiting, Therapeutic Strategy.
AB  - Application of the proteasome inhibitor Bortezomib for the treatment of
      haematopoietic malignancies such as multiple myeloma significantly improves the
      average overall survival of patients. However, one of the most severe side
      effects is the development of peripheral neuropathies caused by neurotoxic
      effects of Bortezomib limiting its therapeutic efficacy. With ONX-0914 a specific
      inhibitor of the beta5i (LMP7)-immunosubunit containing proteasomes was developed
      that targets exclusively the proteasome subtypes mainly expressed in immune cells
      including B lymphocytes as the origin of multiple myeloma. Furthermore,
      immunosubunitspecific inhibitors have been shown to be promising tools for the
      therapy of autoimmune disorders. In the presented study, we analysed the
      concentration-dependent impact of both inhibitors on primary neurons regarding
      survival rate, morphological changes, and overall viability. Our results clearly
      demonstrate that ONX-0914, compared to Bortezomib, is less neurotoxic suggesting
      its potential as a putative antineoplastic drug and as a candidate for the
      treatment of autoimmune disorders affecting the peripheral and/or central nervous
      system.

PMID- 29034114
TI  - Cationic Nanocylinders Promote Angiogenic Activities of Endothelial Cells.
AB  - Polymers have been used extensively taking forms as scaffolds, patterned surface
      and nanoparticle for regenerative medicine applications. Angiogenesis is an
      essential process for successful tissue regeneration, and endothelial cell-cell
      interaction plays a pivotal role in regulating their tight junction formation, a
      hallmark of angiogenesis. Though continuous progress has been made, strategies to
      promote angiogenesis still rely on small molecule delivery or nuanced scaffold
      fabrication. As such, the recent paradigm shift from top-down to bottom-up
      approaches in tissue engineering necessitates development of polymer-based
      modular engineering tools to control angiogenesis. Here, we developed cationic
      nanocylinders (NCs) as inducers of cell-cell interaction and investigated their
      effect on angiogenic activities of human umbilical vein endothelial cells
      (HUVECs) in vitro. Electrospun poly (L-lactic acid) (PLLA) fibers were aminolyzed
      to generate positively charged NCs. The aninolyzation time was changed to produce
      two different aspect ratios of NCs. When HUVECs were treated with NCs, the
      electrostatic interaction of cationic NCs with negatively charged plasma
      membranes promoted migration, permeability and tubulogenesis of HUVECs compared
      to no treatment. This effect was more profound when the higher aspect ratio NC
      was used. The results indicate these NCs can be used as a new tool for the bottom
      up approach to promote angiogenesis.

PMID- 29034115
TI  - Impulse control disorder and response-inhibition alterations in Parkinson's
      disease. A rare case of totally absent functionality of the medial-prefrontal
      cortex and review of literature.
AB  - This report illustrates a Parkinson's disease (PD) patient with impulse-control
      disorder (ICD) and selective impairment in response-inhibition abilities as
      revealed by the performance in a functional magnetic resonance imaging (fMRI)
      anterior cingulate cortex - sensitive go-nogo task. In line with hypothesis on
      the role of response-inhibition disabilities in the arising of impulsivity in PD,
      the patient completely failed the go-nogo task. Moreover, fMRI acquisition
      revealed absent task-sensitive activity in the anterior cingulate cortex, medial
      prefrontal, and orbitofrontal cortices for the contrast nogo versus go, which
      signifying that a hypo-function of this network could be associated with ICD. A
      fronto-striatal and cingulo-frontal dysfunction may reflect impairment in
      metacognitive-executive abilities (such as response-inhibition, action
      monitoring, and error awareness) and promote compulsive repetition of behavior.
      Response-inhibition tasks may be useful in PD post-diagnostic phase, to better
      identify individuals at risk of developing ICD with dopaminergic medication.

PMID- 29034116
TI  - Evaluating a Culturally Tailored HIV Risk Reduction Intervention Among Latina
      Immigrants in the Farmworker Community.
AB  - Latina immigrants in the farmworker community are a vulnerable and understudied
      population at risk of acquiring HIV. Employing a CBPR framework, this pilot study
      was the first to evaluate the efficacy of SEPA, a CDC evidenced-based and
      culturally tailored HIV risk reduction intervention on a cohort of N = 110
      predominantly undocumented Latina immigrants in a farmworker community. Findings
      revealed SEPA was effective in increasing HIV knowledge and decreasing HIV risk
      behaviors. However, no changes in self-efficacy were found in the present sample.
      We posit specific socio-cultural and structural barriers specific to the
      farmworker community not targeted in the original intervention may have hindered
      the program's capacity to influence changes in self-efficacy among this less
      acculturated population. Possible socio-cultural adaptations of the intervention
      to the target population and policy implications are discussed.

PMID- 29034118
TI  - Toward a Patient Registry for Cannabis Use: An Exploratory Study of Patient Use
      in an Outpatient Health-Care Clinic in Oregon.

PMID- 29034119
TI  - Chloride-Tolerant Gold(I)-Catalyzed Regioselective Hydrochlorination of Alkynes.
AB  - We have developed a highly regioselective homogeneous gold(I)-catalyzed anti
      hydrochlorination of unactivated alkynes at room temperature. We have overcome
      the incompatibility between conventional cationic gold catalysts and chloride by
      using a hydrogen-bonding activation of the Au-Cl bond. This approach is scalable,
      exhibits excellent functional group tolerance, and can be conducted in open air.

PMID- 29034117
TI  - Correlates of Cervical Cancer Screening Among Adult Latino Women: A 5-Year Follow
      Up.
AB  - BACKGROUND: Latinas have the highest incidence rates of cervical cancer in the
      United States, and Latinas in the United States are less likely to utilize
      cervical cancer screening. METHOD: We used secondary data analysis of a non
      clinical convenience sample (n=316 women at baseline; n=285 at five-year follow
      up) to examine correlates of cervical cancer screening among adult Latina women.
      Univariate and multiple logistic regression models using Generalized Estimated
      Equations (GEE) algorithm were utilized to assess the influence of the
      independent variables. RESULTS: Women who reported their main healthcare source
      as community health clinics, women who were sexually active, and women who
      reported that a healthcare provider discussed HIV prevention with them were more
      likely to report having a cervical cancer screening (aOR=2.06; CI=1.20, 3.52).
      CONCLUSION: The results suggest a need for continued efforts to ensure that
      medically underserved women (e.g., Latina women) receive counseling and education
      about the importance of preventive cancer screening.

PMID- 29034120
TI  - Modulating the External Facets of Functional Nanocrystals Enabled by Two
      Dimensional Oxide Crystal Templates.
AB  - The nature of the external crystal facets is critical to control the
      (photo)catalytic properties. Two-dimensional materials can expose only one type
      of crystal facet among zero-dimensional (0D), one-dimensional (1D), and two
      dimensional (2D) materials. Controllable tuning of the nature of the external
      crystal facets of 2D materials is highly desirable but very challenging. Here, we
      show that 2D particles with the desirable crystal facet for high-performance
      photocatalytic H2 generation can be obtained by using 2D metal oxide materials
      (i.e., nanosheets of Ca2Nb3O10 and Ti0.87O2) as templates taking consideration of
      the crystal configuration of 2D oxide and target compounds. We demonstrate that
      anatase TiO2 crystals grown on different nanosheet templates exhibit variations
      in photocatalytic hydrogen production rates from aqueous phase methanol solutions
      (6.7%), which can be attributed to the nature of the main crystal facet exposed.
      In view of the large number of 2D materials that have already been synthesized,
      this work offers a key to design and synthesize nanoparticles with the desirable
      specific external crystal facet for (photo)catalysis application.

PMID- 29034121
TI  - Atomically Dispersed Pd-O Species on CeO2(111) as Highly Active Sites for Low
      Temperature CO Oxidation.
AB  - Ceria-supported Pd is a promising heterogeneous catalyst for CO oxidation
      relevant to environmental cleanup reactions. Pd loaded onto a nanorod form of
      ceria exposing predominantly (111) facets is already active at 50  degrees C.
      Here we report a combination of CO-FTIR spectroscopy and theoretical calculations
      that allows assigning different forms of Pd on the CeO2(111) surface during
      reaction conditions. Single Pd atoms stabilized in the form of PdO and PdO2 in a
      CO/O2 atmosphere participate in a catalytic cycle involving very low activation
      barriers for CO oxidation. The presence of single Pd atoms on the Pd/CeO2
      nanorod, corroborated by aberration-corrected TEM and CO-FTIR spectroscopy, is
      considered pivotal to its high CO oxidation activity.

PMID- 29034123
TI  - Ecological Niche Modeling for Filoviruses: A Risk Map for Ebola and Marburg Virus
      Disease Outbreaks in Uganda.
AB  - INTRODUCTION: Uganda has reported eight outbreaks caused by filoviruses between
      2000 to 2016, more than any other country in the world. We used species
      distribution modeling to predict where filovirus outbreaks are likely to occur in
      Uganda to help in epidemic preparedness and surveillance. METHODS: The MaxEnt
      software, a machine learning modeling approach that uses presence-only data was
      used to establish filovirus - environmental relationships. Presence-only data for
      filovirus outbreaks were collected from the field and online sources.
      Environmental covariates from Africlim that have been downscaled to a nominal
      resolution of 1km x 1km were used. The final model gave the relative probability
      of the presence of filoviruses in the study area obtained from an average of 100
      bootstrap runs. Model evaluation was carried out using Receiver Operating
      Characteristic (ROC) plots. Maps were created using ArcGIS 10.3 mapping software.
      RESULTS: We showed that bats as potential reservoirs of filoviruses are
      distributed all over Uganda. Potential outbreak areas for Ebola and Marburg virus
      disease were predicted in West, Southwest and Central parts of Uganda, which
      corresponds to bat distribution and previous filovirus outbreaks areas.
      Additionally, the models predicted the Eastern Uganda region and other areas that
      have not reported outbreaks before to be potential outbreak hotspots. Rainfall
      variables were the most important in influencing model prediction compared to
      temperature variables. CONCLUSIONS: Despite the limitations in the prediction
      model due to lack of adequate sample records for outbreaks, especially for the
      Marburg cases, the models provided risk maps to the Uganda surveillance system on
      filovirus outbreaks. The risk maps will aid in identifying areas to focus the
      filovirus surveillance for early detection and responses hence curtailing a
      pandemic. The results from this study also confirm previous findings that suggest
      that filoviruses are mainly limited by the amount of rainfall received in an
      area.

PMID- 29034125
TI  - The Theory of Planned Behavior and Disaster Preparedness.
AB  - INTRODUCTION: Disaster preparedness is defined as actions that ensure resources
      necessary to carry out an effective response are available before a disaster.
      Disaster preparedness requires a thorough understanding of the factors that
      influence performance or nonperformance of disaster preparedness behaviors (DPB).
      The major aim of this research was to further our understanding of DPB based on
      the theory of planned behavior (TPB). METHOD: This was a cross-sectional study of
      factors determining of DPB in a representative sample of 1233 Tehran inhabitants.
      Measures derived from the TPB were obtained in the unprepared and prepared
      people. RESULTS: Consistent with the theory, intentions to do DPB could the
      person predicted from attitudes, subjective norms, and perceived behavioral
      control with respect to DPB; and actually doing DPB was strongly related to
      intentions and perceptions of control assessed in the prepared people.
      Theoretical and practical implications of these findings are discussed.
      CONCLUSION: An effective intervention will not only have to encourage people of
      the desirability of DPB, but also to provide them with the skills and means to do
      it. The more strongly they can be made to feel that they have control over DPB,
      the more likely they are to carry out their intentions. That is, heightened
      perceived control tends to strengthen people's motivation to do DPB. KEY WORDS:
      theory of planned behavior; disaster;  preparedness.

PMID- 29034122
TI  - Methanol on Anatase TiO2 (101): Mechanistic Insights into Photocatalysis.
AB  - The photoactivity of methanol adsorbed on the anatase TiO2 (101) surface was
      studied by a combination of scanning tunneling microscopy (STM), temperature
      programmed desorption (TPD), X-ray photoemission spectroscopy (XPS), and density
      functional theory (DFT) calculations. Isolated methanol molecules adsorbed at the
      anatase (101) surface show a negligible photoactivity. Two ways of methanol
      activation were found. First, methoxy groups formed by reaction of methanol with
      coadsorbed O2 molecules or terminal OH groups are photoactive, and they turn into
      formaldehyde upon UV illumination. The methoxy species show an unusual C 1s core
      level shift of 1.4 eV compared to methanol; their chemical assignment was
      verified by DFT calculations with inclusion of final-state effects. The second
      way of methanol activation opens at methanol coverages above 0.5 monolayer (ML),
      and methyl formate is produced in this reaction pathway. The adsorption of
      methanol in the coverage regime from 0 to 2 ML is described in detail; it is key
      for understanding the photocatalytic behavior at high coverages. There, a
      hydrogen-bonding network is established in the adsorbed methanol layer, and
      consequently, methanol dissociation becomes energetically more favorable. DFT
      calculations show that dissociation of the methanol molecule is always the key
      requirement for hole transfer from the substrate to the adsorbed methanol. We
      show that the hydrogen-bonding network established in the methanol layer
      dramatically changes the kinetics of proton transfer during the photoreaction.

PMID- 29034124
TI  - Multi-provincial Salmonellosis Outbreak Related to Newly Hatched Chicks and
      Poults: A Genomics Perspective.
AB  - BACKGROUND: A multi-provincial outbreak of Salmonella enterica serovar
      Enteritidis was linked to newly hatched chicks and poults from a single hatchery
      during the spring of 2015. In total, there were 61 human cases that were
      epidemiologically confirmed to be linked to the chicks and poults and the
      outbreak was deemed to have ended in the summer of 2015. METHODS: PulseNet
      Canada, in coordination with the affected provinces, used genome sequencing of
      human and agricultural Salmonella Enteritidis isolates to aid in the
      epidemiological investigation, while also using traditional typing methods such
      as phagetyping and pulsed-field gel electrophoresis (PFGE). RESULTS: All human
      outbreak cases, except one, were Phage Type (PT) 13a. Single nucleotide variant
      analysis (SNV) was able to provide a level of resolution commensurate with the
      results of the epidemiological investigation. SNV analysis was also able to
      separate PT13a outbreak-related isolates from isolates not linked to chicks or
      poults, while clustering some non-PT13a agricultural strains with the outbreak
      cluster. CONCLUSIONS: Based on conventional typing methods (phagetyping or PFGE),
      clinical and agricultural PT13a SE isolates would have been considered as part of
      a related cluster. In contrast, phagetyping would have led to the exclusion of
      several non- PT13a strains that clustered with the outbreak isolates using the
      genome sequence data. This study demonstrates the improved resolution of genome
      sequence analysis for coordinated surveillance and source attribution of both
      human and agricultural SE isolates.

PMID- 29034126
TI  - Development and Characterization of Methylene Blue Oleate Salt-Loaded Polymeric
      Nanoparticles and their Potential Application as a Treatment for Glioblastoma.
AB  - Glioblastoma (GBM) is an aggressive, grade IV brain tumor that develops from
      astrocytes located within the cerebrum, resulting in poor prognosis and survival
      rates following an accepted treatment regimen of surgery, radiation, and
      temozolomide. Thus, development of new therapeutics is necessary. During the last
      two decades, methylene blue (MB) has received increased attention as a potential
      neurotherapeutic due to its duality in brain cancers and neurodegenerative
      diseases. While MB is capable of easily permeating the blood-brain barrier, its
      therapeutic concentrations in GBM are known to induce off-target cytotoxicity and
      thus, another mode of drug delivery must be considered. To this end,
      encapsulation of formerly unusable compounds into nanoparticles (NPs) made from
      the biodegradable/biocompatible, FDA approved co-polymer poly (lactide-co
      glycolide) (PLGA) has been more commonplace when developing novel therapeutics.
      In this study, we formulated and characterized Pluronic F68-coated PLGA NPs
      containing a sodium oleate conjugate of MB (MBOS) via solvent displacement.
      Conjugation of sodium oleate to MB was shown to reduce its release from PLGA NPs
      compared to unmodified MB, leading to potential improvements in drug accumulation
      and therapeutic effectiveness. Our drug-loaded NP preparations, which were ~170
      nm in size and had drug loading values of ~2%, were shown to reduce cell
      viability and cell compartment-specific, as well as overall cell, functions
      equivalenty, if not more so, when compared to free drug in two GBM cell lines.
      Following bio-distribution analysis of free MBOS compared to its nano
      encapsulated counterpart, drug-loaded NPs were shown to more effectively permeate
      the BBB, which could lead to improvements in therapeutic effectiveness upon
      further examination in a tumor-bearing mouse model. Based on these results, we
      believe that the further development and eventual utilization of this
      nanoformulation could lead to an effective GBM therapy that could extend patient
      survival rates.

PMID- 29034129
TI  - Sebaceous carcinoma in situ as a concept and diagnostic entity.
AB  - Although carcinoma in situ has been accepted as a well-established concept and
      diagnostic category, for reasons unknown sebaceous carcinoma in situ has not been
      recognized yet in general pathology or dermatopathology. Such lesions have always
      been misinterpreted as either benign neoplasm or sebaceous carcinoma. In the
      present essay, we provide a convincing account supporting sebaceous carcinoma in
      situ as a valid concept and diagnostic entity via critical literature review and
      histopathological assessment and illustration. Recognizing sebaceous carcinoma in
      situ as a valid concept and diagnostic entity will certainly help to avoid
      misinterpretation and subsequently under or over treatment of such lesions.

PMID- 29034127
TI  - Socio-demographic factors which significantly relate to the prediction of burns
      severity in children.
AB  - BACKGROUND: Burns are considered one of the biggest wounds and the most
      devastating injuries humans can receive as they have prolonged consequences which
      are not only physical, but psychological in addition to the cost of treatment.
      The aim of the study was to explore the relationships between socio-demographic
      factors (SDF) and the incidence and mechanisms of burn injuries in children. The
      objectives were to identify the multiple and various factors responsible for the
      occurrence of significant burns in children; to explore and investigate the
      relationship between these factors; to critically analyse SDF on the incidence
      and mechanisms of burns and to develop a contextual model with a view to
      informing future health care policy and health promotion programmes. METHODS:
      This observational, cross-sectional, descriptive study was performed in a UK
      Paediatric Burn Centre in the West Midlands. The research process followed the
      requirements for obtaining a PhD degree. The quantitative arm of this study
      consisted of a postal questionnaire sent to 228 parents and guardians who had
      visited the Burns Centre with a child during a one-year period (1st May 2011 to
      30th April 2012). For the purpose of coding and analysis, a Statistical Package
      for the Social Science (SPSS) version-19-was used. RESULTS: 160 completed
      questionnaires were returned and analysed. Several key SDF were identified that
      linked to an increase in the incidence of burns in children. Burn injuries was
      significantly higher in children <= 5 years old (P<0.001) and male children
      (58.1%). Burns were more frequent in minority ethnic groups (p<0.001); younger
      aged parents <= 25 years old (p=0.048); and children living with single parents
      (p=0.001). A majority of burns cases resulted from spills (74.4%) and during
      mealtimes (p<0.001). The distributions of the Index Multiple Deprivation (IMD)
      was not the same across ethnic groups (p<0.002), and burns in children was
      significant (p<0.0005) in families living in social accommodation. CONCLUSION:
      The findings potentially may have clinical utility in informing future health
      care policy and health promotion/education programmes. Consideration must be
      given to the timings of such programmes, which relate to treat significant burns
      in non-specialised hospitals.

PMID- 29034128
TI  - Antibiotic sensitivity pattern of Klebsiella species in burn wounds at Bai Jerbai
      Wadia hospital for children, Mumbai, India-a 21 year study.
AB  - In our study, we attempt to look at the sensitivity pattern of the most commonly
      found microorganism in the wound swab of pediatric burn patients at our hospital,
      'Klebsiella', to a number of commonly used antibiotics and to determine whether
      there has been a change in the sensitivities in the 21 year period between 1994
      to 2014. The sensitivity was tested in vitro and antibiotics were administered to
      patients based on laboratory findings. Klebsiella shows a significant change in
      sensitivity pattern over last 21 years. The sensitivity of this organisms to
      various antibiotics tested has reduced over time. The organism out plays most of
      the antibiotics that it is subjected to in vitro. Our efforts should now be
      channelized towards limiting the use of antibiotics or a proper antibiotic policy
      which exercises control of irrelevant and excessive use of antibiotics.

PMID- 29034130
TI  - Dermoscopy of a single plaque on the finger.

PMID- 29034131
TI  - Update: Can breastfeeding and maternal diet prevent atopic dermatitis?

PMID- 29034132
TI  - VOWEL DURATION MEASUREMENT USING DEEP NEURAL NETWORKS.
AB  - Vowel durations are most often utilized in studies addressing specific issues in
      phonetics. Thus far this has been hampered by a reliance on subjective, labor
      intensive manual annotation. Our goal is to build an algorithm for automatic
      accurate measurement of vowel duration, where the input to the algorithm is a
      speech segment contains one vowel preceded and followed by consonants (CVC). Our
      algorithm is based on a deep neural network trained at the frame level on
      manually annotated data from a phonetic study. Specifically, we try two deep
      network architectures: convolutional neural network (CNN), and deep belief
      network (DBN), and compare their accuracy to an HMM-based forced aligner. Results
      suggest that CNN is better than DBN, and both CNN and HMM-based forced aligner
      are comparable in their results, but neither of them yielded the same predictions
      as models fit to manually annotated data.

PMID- 29034134
TI  - Long-distance dating relationships, relationship dissolution, and college
      adjustment.

PMID- 29034136
TI  - Threshold Limit Graphical Approach to Understanding Outcome Predictive Metrics:
      Data from the Osteoarthritis Initiative.
AB  - Scatter plots, bar charts, linear regressions, analysis of variance, and other
      graphics and tests are frequently used to document associations between an
      independent variable and an outcome. However, these methods are also frequently
      limited when understanding how to use an independent variable in subsequent
      research or patient management. A novel graphical approach to visualizing data
      the threshold limit graph-was therefore developed. Publically available data from
      the Osteoarthritis Initiative was used to illustrate the graphical approach to
      understanding the association between the change in joint space width (DeltaJSW,
      independent variable) over four years, and knee symptoms at four years (using the
      Knee Injury and Osteoarthritis Outcome Score [KOOS], dependent variable). Using
      data for 4,202 knees, the traditional scatter plot and linear regression approach
      showed a significant but weak linear relationship between the symptom subscore of
      the KOOS and DeltaJSW. However, the threshold level of DeltaJSW that affects
      symptoms was not clear from the data. The same dataset was then plotted using the
      threshold limit graphical approach, which revealed a non-linear relationship
      between the variables. In contrast to the scatter plot, plotting the average KOOS
      symptom subscore for subgroups of the data, with each subgroup defined using
      sequentially increasing or decreasing DeltaJSW thresholds revealed that symptoms
      got worse with joint space loss, but only when there was a significant amount of
      DeltaJSW. A threshold limit analysis was repeated using small, randomly selected
      subsets of the data (N = ~100) to demonstrate the utility of the technique for
      identifying trends in smaller datasets. The threshold limit graph is a simple,
      graphical approach that may prove helpful in understanding how an independent
      variable might be used to predict outcomes. This approach provides an additional
      option for visualizing and quantifying associations between variables.

PMID- 29034133
TI  - Local Cellular Responses to Titanium Dioxide from Orthopedic Implants.
AB  - We evaluated recently published articles relevant to the biological effects of
      titanium dioxide (TiO2) particles on local endogenous cells required for normal
      bone homeostasis, repair, and implant osseointegration. Structural
      characteristics, size, stability, and agglomeration of TiO2 particles alter the
      viability and behavior of multiple bone-related cell types. Resulting shifts in
      bone homeostasis may increase bone resorption and lead to clinical incidents of
      osteolysis, implant loosening, and joint pain. TiO2 particles that enter cells
      (through endocytosis or Trojan horse mechanism) may further disrupt implant
      retention. We propose that cellular responses to titanium-based nanoparticles
      contribute to pathological mechanisms underlying the aseptic loosening of
      titanium-based metal implants.

PMID- 29034135
TI  - Heterogeneity in Trajectories of Depression in Response to Divorce is Associated
      with Differential Risk for Mortality.
AB  - Divorce is a common stressful event associated with both increased rates of
      depression and mortality. Given evidence of significant individual differences in
      depression following major life stressors, we examined if heterogeneous
      depression responses confer differential risk for mortality. Data from a
      population based longitudinal study was utilized to identify individuals who
      experienced divorce (n=559). Prospective trajectories of depression severity from
      before to after divorce were identified using latent growth mixture modeling, and
      rates of mortality between trajectories were compared as a distal outcome. Four
      trajectories demonstrated strongest model fit: resilience (67%), emergent
      depression (10%), chronic pre-to-post divorce depression (12%), and decreasing
      depression (11%). Mortality base rate was 9.7% by 6 years post-event, and
      depression that emerged due to divorce was associated with significantly greater
      mortality risk compared to resilient (OR, 2.46; 95% CI, 1.05-5.81) and to married
      individuals, while chronic depression was not associated with greater risk.

PMID- 29034137
TI  - Valproic-induced Hyperammonemic Encephalopathy in a Known Case of Epilepsy.
AB  - Valproic acid, a broad-spectrum anticonvulsant drug, commonly causes elevated
      ammonia levels, which is usually asymptomatic in most cases. On rare occasions,
      potentially fatal hyperammonemia-induced encephalopathy can occur. We present a
      case of a 24-year-old female who presented to the emergency department with
      status epilepticus that was being managed with valproic acid. Further workup was
      done because of prolonged postictal state, which revealed increased ammonia
      levels; she was eventually diagnosed with valproic-induced hyperammonemic
      encephalopathy. Discontinuing valproic acid resulted in drastically improved
      symptoms and a gradual decline in ammonia levels. A clinician should be aware of
      rare drug adverse effects and drug interactions to conclusively reach the correct
      diagnosis. A prolonged postictal state should warrant further workup to rule out
      other possible etiologies.

PMID- 29034138
TI  - Testosterone Pellet Associated Dermatitis: Report and Review of Testopel-related
      Cutaneous Adverse Effects.
AB  - Testosterone replacement therapy is a treatment utilized for male hypogonadism. A
      subcutaneous testosterone pellet is a long-acting, slow-release delivery system
      that can be utilized as androgen replacement therapy. A 77-year-old man who was
      treated with testosterone pellets developed dermatitis consisting of erythematous
      plaques and patches on both buttocks and thighs within 28 days following the
      subcutaneous insertion of testosterone pellets. The skin lesions rapidly resolved
      with high-potency topical corticosteroid application. The same cutaneous eruption
      occurred with each subsequent insertion of testosterone pellets. Other cutaneous
      adverse events associated with testosterone pellet insertion include acne,
      hirsutism, and male pattern alopecia. Bleeding, bruising, fibrosis, infections,
      pellet extrusion, scarring, and subcutaneous nodules may also occur at the
      injection site. In summary, testosterone pellet-induced dermatitis is a rare
      adverse cutaneous event, which should be added to the list of potential
      testosterone pellet associated skin side effects.

PMID- 29034139
TI  - Aripiprazole-Induced Neutropenia in a Seven Year-Old Male: A Case Report.
AB  - Blood dyscrasias are the widely known side effect of the second-generation
      antipsychotic medications. Aripiprazole rarely causes hematological side effects
      and it is considered relatively safe. We present the case report of a seven-year
      old male who developed acute neutropenia a week after starting aripiprazole. His
      absolute neutrophil count (ANC) arose spontaneously once the medication was
      stopped. Clinicians should periodically check ANC in the patients taking
      aripiprazole as neutropenia could be lethal in extreme cases. To our knowledge,
      this is the first case report of leukopenia associated with aripiprazole in the
      child and adolescent population.

PMID- 29034141
TI  - Commercial phenoxyacetic herbicides control heavy metal uptake by wheat in a
      divergent way than pure active substances alone.
AB  - BACKGROUND: Impact of two widely used commercial herbicides, i.e. Aminopielik D
      450 SL and Chwastox 300 SL, on the uptake and translocation of selected heavy
      metals in wheat plants Triticum aestivum L. cultivated in the laboratory pot
      experiments was investigated. Mineral-humus, loamy sand soil representative for
      the central part of Poland was applied. Bioavailable, exchangeable and total
      forms of Cd, Co, Cu, Zn, Pb, and Mn were determined. Transfer coefficients,
      translocation, and bioaccumulation factors illustrating metal migration in the
      plant were investigated. RESULTS: Administration of commercial herbicides
      significantly altered heavy metals uptake by wheat in a way distinctively
      different than that observed for the parent chemically pure synthetic auxins,
      i.e. 2,4-D and MCPA. In particular, Aminopielik D 450 SL and Chwastox 300 SL
      prompted heavy metals accumulation in roots as indicated by their high transfer
      coefficients. Further transport to above ground part of the plant was limited and
      element dependent. CONCLUSIONS: This work clearly shows that commercial herbicide
      formulations may act in a distinctively different way than pure active
      ingredients alone.

PMID- 29034140
TI  - Regulation of gene expression by translation factor eIF5A: Hypusine-modified
      eIF5A enhances nonsense-mediated mRNA decay in human cells.
AB  - Nonsense-mediated mRNA decay (NMD) couples protein synthesis to mRNA turnover. It
      eliminates defective transcripts and controls the abundance of certain normal
      mRNAs. Our study establishes a connection between NMD and the translation factor
      eIF5A (eukaryotic initiation factor 5A) in human cells. eIF5A modulates the
      synthesis of groups of proteins (the eIF5A regulon), and undergoes a distinctive
      two-step post-translational modification (hypusination) catalyzed by
      deoxyhypusine synthase and deoxyhypusine hydroxylase. We show that expression of
      NMD-susceptible constructs was increased by depletion of the major eIF5A isoform,
      eIF5A1. NMD was also attenuated when hypusination was inhibited by RNA
      interference with either of the two eIF5A modifying enzymes, or by treatment with
      the drugs ciclopirox or deferiprone which inhibit deoxyhypusine hydroxylase.
      Transcriptome analysis by RNA-Seq identified human genes whose expression is
      coordinately regulated by eIF5A1, its modifying enzymes, and the pivotal NMD
      factor, Upf1. Transcripts encoding components of the translation system were
      highly represented, including some encoding ribosomal proteins controlled by
      alternative splicing coupled to NMD (AS-NMD). Our findings extend and strengthen
      the association of eIF5A with NMD, previously inferred in yeast, and show that
      hypusination is important for this function of human eIF5A. In addition, they
      advance drug-mediated NMD suppression as a therapeutic opportunity for nonsense
      associated diseases. We propose that regulation of mRNA stability contributes to
      eIF5A's role in selective gene expression.

PMID- 29034142
TI  - Epidemiologic Approaches for Studying Assisted Reproductive Technologies: Design,
      Methods, Analysis and Interpretation.
AB  - PURPOSE: While considerable progress has been made since the advent of assisted
      reproductive technology (ART), the field remains a complex and challenging one
      for clinicians and researchers alike. This review discusses some of the most
      salient issues pertaining to the study of ART and whenever possible suggestions
      on how to address them. RECENT FINDINGS: More than 5 million babies have been
      born through ART to date, representing up to 4% of all births worldwide. While
      technologies continue to evolve and demand for treatment grows, it is more
      important than ever to conduct rigorous and timely research to help guide
      clinical practice that is safe and effective, and that minimizes potential short-
      and long-term adverse outcomes to mother and child. SUMMARY: ART research will
      require exceedingly more sophisticated research methods, designs, and analyses
      that are rooted in a reproductive epidemiological framework in order to improve
      future research and ultimately promote better outcomes for all subfertile couples
      and their children.

PMID- 29034143
TI  - Decision aids to increase living donor kidney transplantation.
AB  - PURPOSE OF REVIEW: For the more than 636,000 adults with end-stage renal disease
      (ESRD) in the U.S., kidney transplantation is the preferred treatment compared to
      dialysis. Living donor kidney transplantation (LDKT) comprised 31% of kidney
      transplantations in 2015, an 8% decrease since 2004. We aimed to summarize the
      current literature on decision aids that could be used to improve LDKT rates.
      RECENT FINDINGS: Decision aids are evidence-based tools designed to help patients
      and their families make difficult treatment decisions. LDKT decision aids can
      help ESRD patients, patients' family and friends, and healthcare providers engage
      in treatment decisions and thereby overcome multifactorial LDKT barriers.
      SUMMARY: We identified 12 LDKT decision aids designed to provide information
      about LDKT, and/or to help ESRD patients identify potential living donors, and/or
      to help healthcare providers make decisions about treatment for ESRD or living
      donation. Of these, 4 were shown to be effective in increasing LDKT, donor
      inquiries, LDKT knowledge, and willingness to discuss LDKT. Although each LDKT
      decision aid has limitations, adherence to decision aid development guidelines
      may improve decision aid utilization and access to LDKT.

PMID- 29034145
TI  - Swift tuning from spherical molybdenum microspheres to hierarchical molybdenum
      disulfide nanostructures by switching from solvothermal to hydrothermal synthesis
      route.
AB  - Herein, we report the synthesis of metallic molybdenum microspheres and
      hierarchical MoS2 nanostructures by facile template-free solvothermal and
      hydrothermal approach, respectively. The morphological transition of the Mo
      microspheres to hierarchical MoS2 nanoflower architectures is observed to be
      accomplished with change in solvent from ethylenediamine to water. The resultant
      marigold flower-like MoS2 nanostructures are few layers thick with poor
      crystallinity while spherical ball-like molybdenum microspheres exhibit better
      crystalline nature. This is the first report pertaining to the synthesis of Mo
      microspheres and MoS2 nanoflowers without using any surfactant, template or
      substrate in hydro/solvothermal regime. It is opined that such nanoarchitectures
      of MoS2 are useful candidates for energy related applications such as hydrogen
      evolution reaction, Li ion battery and pseudocapacitors. Inquisitively, metallic
      Mo can potentially act as catalyst as well as fairly economical Surface Enhanced
      Raman Spectroscopy (SERS) substrate in biosensor applications.

PMID- 29034144
TI  - Exercise Treatments for Psychosis: A Review.
AB  - Schizophrenia is a devastating mental illness that has profound effects on a
      person's health and quality of life. Exercise represents a promising new
      treatment option that may supplement current psychosocial and pharmacological
      interventions for psychosis. A large body of work suggests that exercise can
      improve cardio-metabolic and health behavior and facilitate neurogenesis in areas
      of the brain that are notably impacted by psychosis. Recent efforts to
      incorporate exercise as either stand-alone or adjunctive treatment for
      individuals with schizophrenia range from yoga and light stretching to moderately
      intense walking, bike riding, or team sports. These interventions suggest that
      moderately intense exercise may be beneficial for improving both positive and
      negative symptomatology, cognition and functioning. Indeed, exercise may be
      beneficial for decreasing risk factors for a wide range of health problems often
      observed in patients with schizophrenia, including weight gain and metabolic
      syndrome as well as tobacco and substance use. Given the positive results from
      interventions in schizophrenia patients, there is an impetus for incorporating
      exercise in the early stages of the disorder. Notably, individuals at ultrahigh
      risk (UHR) for psychosis report more sedentary behavior and perceive less benefit
      from exercise; interventions prior to the onset of the disorder may be helpful
      for increasing health behaviors, perhaps delaying or preventing the onset of
      psychosis. Taken together, for individuals with psychosis, exercise may provide
      holistic benefits for the neural to the social impairments.

PMID- 29034146
TI  - Course of respiratory allergy by treatment strategy based on German routine data.
AB  - PURPOSE: Allergic respiratory diseases represent a global health problem. The two
      major treatment strategies are symptom treatment and specific immunotherapy
      (SIT). SIT is considered the only causal treatment option available with the
      ability to alter the course of the disease. This study aims to describe the
      course of disease and medication of respiratory allergy across treatment
      strategies and disease groups. METHODS: The analysis is based on routine data
      from a German statutory health insurance. The patient cohort is observed from
      2007-2012. For each year based on assured outpatient diagnoses patients are
      assigned to a disease group: rhinitis, asthma or both diseases. Additionally,
      prescribed medication is considered. Treatment comparisons are based on matched
      pairs. RESULTS: The study population comprises 165,446 patients with respiratory
      allergy. In 2007 the most frequent disease group is rhinitis (70%), followed by
      asthma (16%) and both diseases (14%). During the observation period a second
      allergic respiratory diagnosis occurs only in about 12% of rhinitis patients and
      28% of asthma patients. In about 50% of patients with both diseases one of the
      diagnoses is omitted. These patients are more likely to no longer report their
      asthma diagnosis when receiving immunotherapy compared to symptom treatment.
      Furthermore immunotherapy reduces the frequency of asthma medication use.
      CONCLUSIONS: Results of detailed analysis of diagnoses reflect the alternating
      nature of allergic diseases. Although limited by accuracy of documentation and
      the lack of clinical information, the comparison of treatment strategies shows
      some advantages of immunotherapy regarding course of disease and asthma
      medication use.

PMID- 29034147
TI  - Elementary physical education: A focus on fitness activities and smaller class
      sizes are associated with higher levels of physical activity.
AB  - Optimizing physical activity during physical education is necessary for children
      to achieve daily physical activity recommendations. The purpose of this study was
      to examine the relationship among various contextual factors with accelerometer
      measured physical activity during elementary physical education. Data were
      collected during 2015-2016 from 281 students (1st-5th grade, 137 males, 144
      females) from a private school located in a metropolitan area of Utah in the U.S.
      Students wore accelerometers for 12 consecutive weeks at an accelerometer wear
      frequency of 3 days per week during physical education. A multi-level general
      linear mixed effects model was employed to examine the relationship among various
      physical education contextual factors and percent of wear time in moderate-to
      vigorous physical activity (%MVPA), accounting for clustering of observations
      within students and the clustering of students within classrooms. Explored
      contextual factors included grade level, lesson context, sex, and class size.
      Main effects and interactions among the factors were explored in the multi-level
      models. A two-way interaction of lesson context and class size on %MVPA was shown
      to be statistically significant. The greatest differences were found to be
      between fitness lessons using small class sizes compared to motor skill lessons
      using larger class sizes (beta = 14.8%, 95% C.I. 5.7%-23.9% p < 0.001). Lessons
      that included a focus on fitness activities with class sizes that were < 25
      students associated with significantly higher %MVPA during elementary physical
      education.

PMID- 29034148
TI  - Does a grill menu redesign influence sales, nutrients purchased, and consumer
      acceptance in a worksite cafeteria?
AB  - Worksite cafeterias are compelling venues to improve diet quality through
      environmental changes. We conducted a pre-post study to evaluate how a cafeteria
      initiated grill menu redesign influenced sales, revenue, and nutrient content of
      foods purchased. Secondly, we evaluated consumer opinions about menu changes to
      inform practices for worksite environment interventions. Monthly sales data (2012
      2015) were used to compute gross sales and revenue of entrees and side dishes pre
      post menu changes. Alternative protein sources replaced red meat; nutrient
      composition and nutrients purchased were compared using Food Pro software.
      Consumer responses were queried using online surveys; open-ended responses were
      analyzed using NVivo. Differences in sales and nutrient content pre-post menu
      redesign were tested with Wilcoxon Rank Sum tests. Gross sales of entrees (61 vs.
      222 servings/month; p = 0.01) and side dishes (120 vs. 365 servings/month; p =
      0.001) increased more than three-fold post-menu changes. Revenue from entrees
      (312 vs. 1144 USD/month; p = 0.01) and side dishes (238 vs. 914 USD/month; p =
      0.001) also increased; per entree, consumers purchased significantly more
      unsaturated fat (5 g), and less saturated fat (3 g) and sodium (100 mg). For side
      dishes, they purchased fewer calories (48 kcal) and unsaturated fat (2.9 g), but
      more fiber (1.8 g), and sodium (260 mg). Four themes emerged from consumer
      responses: the importance of 1) variety, novelty, choice; 2) cost, affordability,
      value; 3) health; and 4) food quality, taste. Menu redesign can improve nutrient
      content, while also increasing sales and revenue. Multi-dimensional assessment of
      the nutritional, consumer, and retailer implications is desirable practice for
      enacting similar environmental changes.

PMID- 29034150
TI  - Optical Coherence Tomography Angiography, the powerful new imaging modality for
      clinical ophthalmology.

PMID- 29034149
TI  - Limited indications of tax stamp discordance and counterfeiting on cigarette
      packs purchased in tobacco retailers, 97 counties, USA, 2012.
AB  - Increasing the per-unit cost of tobacco products is one of the strongest
      interventions for tobacco control. In jurisdictions with higher taxes in the
      U.S., however, cigarette pack litter studies show a substantial proportion of
      littered packs lack the appropriate tax stamp. More limited but still present
      counterfeiting also exists. We sought to examine the role of tobacco retailers as
      a source for untaxed and counterfeit products. Data collectors purchased Newport
      Green (menthol) or Marlboro Red cigarette packs in a national probability-based
      sample of tobacco retailers (in 97 counties) from June-October 2012. They made no
      effort to buy counterfeit or untaxed cigarettes. In this cross-sectional study,
      we assessed the presence, tax authority, and type (low-tech thermal vs.
      encrypted) of cigarette pack tax stamps; concordance of tax stamps with where the
      pack was purchased; and, for Marlboro cigarettes, publicly available visible
      indicators of counterfeiting. We purchased 2147 packs of which 2033 had tax
      stamps. Packs missing stamps were in states that do not require them. We found
      very limited discordance between store location and tax stamp(s) (< 1%). However,
      a substantial minority of cigarette packs had damaged tax stamps (13%). This
      occurred entirely with low-tech tax stamps and was not identified with encrypted
      tax stamps. We found no clear evidence of counterfeit products. Almost all tax
      stamps matched the location of purchase. Litter studies may be picking up legal
      tax avoidance instead of illegal tax evasion or, alternatively, purchase of
      illicit products requires special request by the purchaser.

PMID- 29034151
TI  - Aqueous shunt implantation in glaucoma.
AB  - Aqueous shunts or glaucoma drainage devices are increasingly utilized in the
      management of refractory glaucoma. The general design of the most commonly-used
      shunts is based on the principles of the Molteno implant: ie. a permanent
      sclerostomy (tube), a predetermined bleb area (plate) and diversion of aqueous
      humour to the equatorial region and away from the limbal subconjunctival space.
      These three factors make aqueous shunts more resistant to scarring as compared to
      trabeculectomy. The two most commonly used shunts are the Ahmed Glaucoma Valve,
      which contains a flow-restrictor, and the non-valved Baervedlt Glaucoma Implant.
      While the valved implants have a lower tendency to hypotony and related
      complications, the non-valved implants with larger, more-biocompatible end plate
      design, achieve lower intraocular pressures with less encapsulation. Non-valved
      implants require additional suturing techniques to prevent early hypotony and a
      number of these methods will be described. Although serious shunt-related
      infection is rare, corneal decompensation and diplopia are small but significant
      risks.

PMID- 29034152
TI  - Association of fatty acid-binding protein 2 and fat mass and obesity-associated
      gene polymorphism with primary open-angle glaucoma.
AB  - PURPOSE: The present study was carried out to investigate the association of
      fatty acid-binding protein 2 (FABP2) and fat mass and obesity-associated (FTO)
      gene polymorphism with primary open-angle glaucoma (POAG) cases and controls.
      MATERIALS AND METHODS: This study includes 122 POAG cases and 112 controls. FABP2
      and FTO gene polymorphisms in cases and controls were evaluated by polymerase
      chain reaction-restriction fragment length polymorphism method. RESULTS: The mean
      ages were 49.88 +/- 12.34 and 53.74 +/- 11.87 years in POAG cases and control
      groups, respectively. The FABP2 gene AA, AT, TT genotype frequencies were 12.90%,
      62.40%, 24.80% in POAG cases and 20.60%, 64.70%, 14.70% in healthy controls,
      respectively. The frequencies of A and T allele in POAG cases were 44.06% and
      55.94% as compared to 52.94% and 47.06% in the controls. The FTO gene AA, AT, TT
      genotype frequencies were 2.00%, 79.20%, 18.80% in cases and 0%, 75.50%, 24.50%
      in healthy controls, respectively. The frequencies of A and T allele in POAG
      cases were 41.58% and 58.42% as compared to 37.75% and 62.25% in the controls. No
      significant difference in the frequencies of FABP2 and FTO genotype was found
      between POAG cases and controls. CONCLUSION: We could not identify the possible
      association of FABP2 and FTO gene polymorphism with POAG; however, further
      studies with larger sample size in different population are require to clarify
      the role of FABP2 and FTO genes in susceptibility to POAG.

PMID- 29034153
TI  - Efficacy of frontalis suspension with silicone rods in ptosis patients with poor
      Bell's phenomenon.
AB  - PURPOSE: The purpose of the study was to evaluate the efficacy of silicone rods
      as frontalis sling for correction of ptosis associated with poor Bell's
      phenomenon in specific situations. MATERIALS AND METHODS: A retrospective
      interventional case series of 25 eyes of 19 patients who underwent frontalis
      suspension surgery with silicone rods for ptosis correction from May 2006 to
      April 2011, was performed. Inclusion criteria included severe ptosis with poor
      Bell's phenomenon. Patient evaluation included clinical history and other
      relevant parameters of ptosis measurement. Final outcome measurements included
      postoperative lid height, lagophthalmos, complications, need for reoperation, and
      patient satisfaction. RESULTS: Mean age at presentation was 25.72 +/- 2.2 years.
      The sex ratio of male: female was 1.11. The causes of ptosis included chronic
      progressive external ophthalmoplegia (CPEO) in 11 eyes (44%), oculopharyngeal
      dystrophy in 2 (8%), third cranial nerve palsy in 7 (28%), traumatic in three
      eyes (12%), and iatrogenic postoperative ptosis (after orbital tumor excision) in
      two eyes (8%). The postoperative palpebral fissure height and margin reflex
      distance improved significantly (P = 0.0001). Extrusion of the sling and
      granuloma formation occurred in two eyes each, and these patients had to undergo
      sling removal. One patient developed mild exposure keratopathy and was managed
      conservatively. CONCLUSION: Silicone is an effective material for use in
      frontalis suspension in the management of severe ptosis with poor Bell's
      phenomenon. The elastic nature of silicone rod makes it an ideal suspensory
      material for patients with CPEO or third nerve palsy.

PMID- 29034154
TI  - Intraocular pressure monitoring by rebound tonometry in children with myopia.
AB  - BACKGROUND/PURPOSE: Topical atropine treatment is generally accepted to retard
      the progression of myopia, but it is associated with side effects such as
      photophobia and elevation of intraocular pressure (IOP). IOP measurements in
      children are challenging. The traditional applanation tonometry by direct contact
      with the cornea will require patient's cooperation. The rebound tonometer, using
      a dynamic electromechanical method for measuring IOP, shows good correlation with
      traditional tonometry. The purpose of this study is to evaluate the IOP of myopic
      children under atropine treatment using rebound tonometer and to compare the
      characteristics between rebound tonometry and applanation tonometry. METHODS:
      This study is a prospective study measuring IOP by rebound tonometer in myopic
      children under regular low-dose atropine treatment. We recruited children with
      refraction error showing myopia over -0.5 D with 0.15%, 0.3%, or 0.5% atropine
      eye drops use every night or every other night for myopia control. Children with
      treatment duration of atropine <1 month were excluded from the study. IOP
      measurements were performed by applanation tonometer (Tono-Pen XL, Reichert) and
      rebound tonometer (ICARE). The reliability of rebound tonometer was analyzed with
      percentage. Comparison of IOP between rebound tonometer and applanation tonometry
      was presented. RESULTS: The rebound tonometry was well tolerated by all
      participants and caused no complaints, discomfort, or adverse events. Totally 42
      myopic eyes of 42 subjects were included in the study. The average age of these
      participants was 10 years old, range from 5 to 16. Median = 10 years old. The
      average IOP of the right eye by rebound tonometer was 17.4 +/- 3 mmHg, and 17.1
      +/- 3 mmHg by applanation tonometry. Nearly 19%, 33%, and 24% of difference of
      IOP readings between rebound tonometer and Tono-Pen applanation are within 0
      mmHg, 1 mmHg, and 1-2 mmHg, respectively. CONCLUSIONS: Rebound tonometry has good
      correlation with applanation tonometry and 76.1% of differences between two
      tonometers are <2 mmHg. The advantage of drop-free rebound tonometry has made it
      easier to obtain IOP readings in myopia children under atropine treatment.

PMID- 29034155
TI  - A mobile team for screening of retinopathy of prematurity in India: Cost -
      effectiveness, outcomes, and impact assessment.
AB  - PURPOSE: To study the cost effectiveness, outcomes and impact of retinopathy of
      prematurity (ROP) screening and management model for urban neonatal intensive
      care units (NICUs). STUDY DESIGN: Public health intervention study. METHODS: This
      study was conducted in 2013. Staff of a mobile unit assessed all infants aged
      less than 34 weeks of Gestation age at birth and/or birth weight 1700 GM or less
      admitted in five NICUs between 2013 and 2015. A trained ophthalmologist performed
      bedside ROP screening through dilated pupils using indirect ophthalmoscope. ROP
      was graded and managed as per the International Classification of Retinopathy of
      Prematurity treatment guidelines. Counseling and laser treatment were the
      interventions. The incidence, grade and determinants of ROP were estimated.
      Direct and indirect costs were calculated to estimate the unit cost of screening
      and managing a child with ROP using the model. RESULTS: The study sample included
      102 preterm/underweight infants. The prevalence of ROP of different grades in
      either eye was 32% (95% Confidence Intervals (CI): 23.2-41.5). ROP stage I was
      present in 75% of these eyes. The model could help in preventing/reducing visual
      disability in 4 infants with advanced stages of ROP. The unit cost of ROP
      screening, identifying one child with ROP and addressing visual disability due to
      ROP was US $ 198.9, 596.7 and 4,137.4 respectively. CONCLUSION: A mobile
      screening is likely feasible and cost-effective method to detect ROP and offer
      timely intervention for NICU in urban areas with limited resources.

PMID- 29034157
TI  - Endoscope-assisted vitrectomy in the management of retinal detachment with
      corneal opacity.
AB  - A 51-year-old male who had suffered from right eye rhegmatogenous retinal
      detachment with proliferative vitreoretinopathy received surgical treatments
      which included the following procedures: lens extraction, scleral buckle,
      vitrectomy, membrane peeling, photocoagulation, and silicone oil injection. The
      presenting visual acuity of the right eye was light perception. Slit-lamp
      examination revealed corneal opacity without a visible fundus. B-scan
      ultrasonography revealed retinal detachment. Endoscope-assisted vitrectomy was
      then performed in December 2014. The procedure also included photocoagulation and
      silicone oil tamponade. Postoperative follow-up confirmed retinal attachment
      through B-scan ultrasonography. To assess the feasibility of a penetrating
      keratoplasty, an endoscopic evaluation was performed in May 2015. A temporal
      retinal break was noted, and photocoagulation was applied around the break as
      well as the peripheral retina. Endoscopy later confirmed the retinal attachment.
      From the present case, we concluded that endoscope-assisted vitrectomy could be
      an option for patients with corneal opacity indicated for vitreoretinal surgery.
      We report the first case of endoscope-assisted vitrectomy in the management of
      retinal detachment in Taiwan.

PMID- 29034158
TI  - Malignant choroidal melanoma with suspected vitreous seeding - A case report.
AB  - Retinal perforation with vitreous seeding is an uncommon condition of treatment
      naive choroidal malignant melanoma. We reported a 52-year-old male who had a
      pigmented tumor protruding from choroid of his right eye. He had only black
      shadow sensation for 4 months then a rapid deterioration of vision. Fundus
      examination showed vitreous haze with many pigmented materials. B-scan
      ultrasonography revealed a mass with low internal reflectivity and vitreous
      opacity. The eyeball was enucleated and a stage IIIA melanoma was confirmed by
      the pathologist. No local recurrences or metastases were found during 31-month
      follow-up. Although vitreous seeding may indicate rapid tumor growth, early
      enucleation may insure a better prognosis.

PMID- 29034156
TI  - Intraocular lens opacification after Descemet's stripping automated endothelial
      keratoplasty.
AB  - Compared with conventional penetrating keratoplasty, Descemet's stripping
      automated endothelial keratoplasty (DSAEK) more effectively maintain global
      integrity and rapid vision rehabilitation with less ocular surface disorders in
      patients with endothelial dysfunction. Here, we report a case of a 76-year-old
      woman who experienced opacification of a hydrophilic intraocular lens (IOL)
      approximately 10 months after DSAEK. The patient with no history of systemic
      disease developed pseudophakic bullous keratopathy in the right eye 2 years after
      undergoing cataract surgery. The best-corrected visual acuity (BCVA) of the right
      eye was Snellen 0.01 when presented to our hospital. DSAEK was arranged and
      performed smoothly. However, the graft detached over the upper part of the cornea
      on postoperative day 1. Thus, rebubbling was performed immediately. After the
      procedure, the graft was well attached, and the cornea became clear gradually.
      The BCVA returned to Snellen 0.6. However, progressive opacification over the
      anterior surface of the IOL was observed 10 months postoperatively. Vision
      deteriorated to 0.5 with various refractive errors during 2-year follow-up. IOL
      exchange may be considered if the vision is getting worse. IOL opacification may
      result from a direct contact between the IOL surface and exogenous air,
      particularly in a hydrophilic IOL, and can be a rare but significant complication
      after DSAEK. Clinicians planning to perform DSAEK should consider the composition
      of the IOL, the amount of intracameral air, duration of air filling, and high
      intraocular pressure.

PMID- 29034159
TI  - Autoimmune retinopathy associated with systemic lupus erythematosus: A diagnostic
      dilemma.
AB  - Visual loss in systemic lupus erythematosus (SLE) due to autoimmune retinopathy
      (AIR) is rare and easily misdiagnosed as hydroxychloroquine retinopathy. We
      report the rare clinical presentation of severe visual loss in a patient with SLE
      due to nonparaneoplastic AIR as differentiated from hydroxychloroquine toxicity.
      A 70-year-old female diagnosed and treated for lupus for 17 years and had been
      taking hydroxychloroquine for 15 years. Over the past 2 years, she developed
      progressive peripheral visual loss oculus uterque which rapidly advanced in the
      latter 6 months. Hydroxychloroquine toxicity was initially suspected, but
      diagnostic testing revealed a retinal degeneration. Antiretinal autoantibody
      testing using Western blot analysis revealed autoantibodies against 44-kDa, 46
      kDa (anti-enolase), and 68-kDa proteins. Visual acuity improved in the first 6
      months of treatment with mycophenolate mofetil. Our case suggests that AIR should
      be considered in the differential diagnosis of rapid, severe visual loss in
      patients with hydroxychloroquine treatment.

PMID- 29034160
TI  - Eosinophilic plasmacytic conjunctivitis concurrent with gingival fistula caused
      by Schizophyllum commune in a captive cheetah (Acinonyx jubatus).
AB  - We describe for the first time the diagnosis of Schizophyllum commune infection
      in a captive cheetah. Eosinophilic plasmacytic conjunctivitis was detected
      histopathologically in a biopsy specimen. Both a second surgical specimen and
      drainage fluid from a gingival mass and fistula contained fungal hyphae in giant
      cells with granulomatous inflammation. Allergic S. commune mycosis was suspected
      at this point. A monokaryotic isolate was characterized morphologically, and then
      identified genetically. Treatment with itraconazole and pimaricin was effective.

PMID- 29034161
TI  - Going green? Ex-post valuation of a multipurpose water infrastructure in Northern
      Italy.
AB  - A contingent valuation approach is used to estimate how households value
      different multipurpose infrastructures (conventional or green) for managing flood
      risk and water pollution. As a case study we consider the Gorla Maggiore water
      park located in the Lombardy Region, in Northern Italy. The park is a neo
      ecosystem including an infrastructure to treat waste water and store excess rain
      water, built in 2011 on the shore of the Olona River in an area previously used
      for poplar plantation. This park is the first one of this type built in Italy. A
      novel aspect of our research is that it not only considers the values people hold
      for different water ecosystem services (pollution removal, recreative use,
      wildlife support, flood risk reduction), but also their preferences for how those
      outcomes are achieved (through conventional or green infrastructures). The
      results indicate that the type of infrastructure delivering the ecosystem
      services does have an impact on individuals' preferences for freshwater ecosystem
      services. Households are willing to pay from 6.3 to 7.1 euros per year for a
      green infrastructure (compared to a conventional one), with a premium up to 16.5
      euros for a surrounding made of a park. By considering the type of infrastructure
      within the choice model, we gain a richer understanding of the relationship
      between social welfare and freshwater ecosystem services.

PMID- 29034162
TI  - EEG source connectivity to localize the seizure onset zone in patients with drug
      resistant epilepsy.
AB  - Electrical source imaging (ESI) from interictal scalp EEG is increasingly
      validated and used as a valuable tool in the presurgical evaluation of epilepsy
      as a reflection of the irritative zone. ESI of ictal scalp EEG to localize the
      seizure onset zone (SOZ) remains challenging. We investigated the value of an
      approach for ictal imaging using ESI and functional connectivity analysis (FC).
      Ictal scalp EEG from 111 seizures in 27 patients who had Engel class I outcome at
      least 1 year following resective surgery was analyzed. For every seizure, an
      artifact-free epoch close to the seizure onset was selected and ESI using LORETA
      was applied. In addition, the reconstructed sources underwent FC using the
      spectrum-weighted Adaptive Directed Transfer Function. This resulted in the
      estimation of the SOZ in two ways: (i) the source with maximal power after ESI,
      (ii) the source with the strongest outgoing connections after combined ESI and
      FC. Next, we calculated the distance between the estimated SOZ and the border of
      the resected zone (RZ) for both approaches and called this the localization error
      ((i) LEpow and (ii) LEconn respectively). By comparing LEpow and LEconn, we
      assessed the added value of FC. The source with maximal power after ESI was
      inside the RZ (LEpow = 0 mm) in 31% of the seizures and estimated within 10 mm
      from the border of the RZ (LEpow <= 10 mm) in 42%. Using ESI and FC, these
      numbers increased to 72% for LEconn = 0 mm and 94% for LEconn <= 10 mm. FC
      provided a significant added value to ESI alone (p < 0.001). ESI combined with
      subsequent FC is able to localize the SOZ in a non-invasive way with high
      accuracy. Therefore it could be a valuable tool in the presurgical evaluation of
      epilepsy.

PMID- 29034163
TI  - Identification of autism spectrum disorder using deep learning and the ABIDE
      dataset.
AB  - The goal of the present study was to apply deep learning algorithms to identify
      autism spectrum disorder (ASD) patients from large brain imaging dataset, based
      solely on the patients brain activation patterns. We investigated ASD patients
      brain imaging data from a world-wide multi-site database known as ABIDE (Autism
      Brain Imaging Data Exchange). ASD is a brain-based disorder characterized by
      social deficits and repetitive behaviors. According to recent Centers for Disease
      Control data, ASD affects one in 68 children in the United States. We
      investigated patterns of functional connectivity that objectively identify ASD
      participants from functional brain imaging data, and attempted to unveil the
      neural patterns that emerged from the classification. The results improved the
      state-of-the-art by achieving 70% accuracy in identification of ASD versus
      control patients in the dataset. The patterns that emerged from the
      classification show an anticorrelation of brain function between anterior and
      posterior areas of the brain; the anticorrelation corroborates current empirical
      evidence of anterior-posterior disruption in brain connectivity in ASD. We
      present the results and identify the areas of the brain that contributed most to
      differentiating ASD from typically developing controls as per our deep learning
      model.

PMID- 29034165
TI  - Nodular onchocercosis in red deer (Cervus elaphus) in Sweden.
AB  - The presence of subcutaneous nodular onchocercosis was investigated at slaughter
      of 151 red deer (Cervus elaphus) (107 juveniles and 44 adults) between October
      December 2015. The prevalence of subcutaneous nodules was 56%. Nodules were
      located in the lumbar region of the back in 96% of the cases, and 38% of the
      infected red deer had additional parasitic nodules in other body locations, such
      as rump, thorax, forelimbs and neck. The number of nodules per deer was 1-10 in
      two-thirds of the affected animals, and only 2% had more than 50 nodules.
      Significant differences in prevalence of nodule presence were found between adult
      (81%) and juvenile red deer less than two years of age (45%) (p = 0.0001).
      Species confirmation and identification was done on 14 randomly selected nodules
      taken from the lumbar region of 14 deer of different geographical origin, by
      sequencing the mitochondrial 12S, 16S and nad5 gene fragments. The sequences were
      more or less identical (12S = 99-100%; 16S = 93-100%; nad5 = 92-100%) to
      previously published sequences for Onchocerca flexuosa. The high prevalence of
      nodular onchocercosis caused by O. flexuosa in red deer in Sweden shows that the
      investigated areas in the southern third of Sweden have favorable vector
      (simuliids and ceratopogonids) conditions and suitable environment for the
      maintenance of the parasite. To our knowledge, this is the first systematic study
      of O. flexuosa in red deer in Sweden.

PMID- 29034164
TI  - Aberrant brain functional connectivity in newborns with congenital heart disease
      before cardiac surgery.
AB  - Newborns with congenital heart disease (CHD) requiring open heart surgery are at
      increased risk for neurodevelopmental disabilities. Recent quantitative MRI
      studies have reported disrupted growth, microstructure, and metabolism in fetuses
      and newborns with complex CHD. To date, no study has examined whether functional
      brain connectivity is altered in this high-risk population after birth, before
      surgery. Our objective was to compare whole-brain functional connectivity of
      resting state networks in healthy, term newborns (n = 82) and in term neonates
      with CHD before surgery (n = 30) using graph theory and network-based statistics.
      We report for the first time intact global network topology - efficient and
      economic small world networks - but reduced regional functional connectivity
      involving critical brain regions (i.e. network hubs and/or rich club nodes) in
      newborns with CHD before surgery. These findings suggest the presence of early
      life brain dysfunction in CHD which may be associated with neurodevelopmental
      impairments in the years following cardiac surgery. Additional studies are needed
      to evaluate the prognostic, diagnostic and surveillance potential of these
      findings.

PMID- 29034166
TI  - Post-lobotomy epilepsy illustrated by the story of Ellinor Hamsun, the daughter
      of the famous Norwegian author Knut Hamsun.
AB  - In Scandinavia, at least 11.500 people were lobotomized in the period 1939-1983.
      Beside grave personality changes, the surgery caused epilepsy in 10-35% of the
      patients. Moreover, many died due to perioperative bleedings, convulsive status
      epilepticus or SUDEP. Most of the stories of these people are anonymous and their
      post-lobotomy lives are scarcely documented. If it was not for the fact that
      Ellinor Hamsun (1916-1987) was the daughter of the famous Nobel Prize winning
      Norwegian author Knut Hamsun, her lobotomy story and the subsequent iatrogenic
      epilepsy would probably have remained unknown.

PMID- 29034167
TI  - Characterization of lens based photoacoustic imaging system.
AB  - Some of the challenges in translating photoacoustic (PA) imaging to clinical
      applications includes limited view of the target tissue, low signal to noise
      ratio and the high cost of developing real-time systems. Acoustic lens based PA
      imaging systems, also known as PA cameras are a potential alternative to
      conventional imaging systems in these scenarios. The 3D focusing action of lens
      enables real-time C-scan imaging with a 2D transducer array. In this paper, we
      model the underlying physics in a PA camera in the mathematical framework of an
      imaging system and derive a closed form expression for the point spread function
      (PSF). Experimental verification follows including the details on how to design
      and fabricate the lens inexpensively. The system PSF is evaluated over a 3D
      volume that can be imaged by this PA camera. Its utility is demonstrated by
      imaging phantom and an ex vivo human prostate tissue sample.

PMID- 29034168
TI  - Quantitative comparison of PZT and CMUT probes for photoacoustic imaging:
      Experimental validation.
AB  - Photoacoustic (PA) signals are short ultrasound (US) pulses typically
      characterized by a single-cycle shape, often referred to as N-shape. The spectral
      content of such wideband signals ranges from a few hundred kilohertz to several
      tens of megahertz. Typical reception frequency responses of classical
      piezoelectric US imaging transducers, based on PZT technology, are not
      sufficiently broadband to fully preserve the entire information contained in PA
      signals, which are then filtered, thus limiting PA imaging performance.
      Capacitive micromachined ultrasonic transducers (CMUT) are rapidly emerging as a
      valid alternative to conventional PZT transducers in several medical ultrasound
      imaging applications. As compared to PZT transducers, CMUTs exhibit both higher
      sensitivity and significantly broader frequency response in reception, making
      their use attractive in PA imaging applications. This paper explores the
      advantages of the CMUT larger bandwidth in PA imaging by carrying out an
      experimental comparative study using various CMUT and PZT probes from different
      research laboratories and manufacturers. PA acquisitions are performed on a
      suture wire and on several home-made bimodal phantoms with both PZT and CMUT
      probes. Three criteria, based on the evaluation of pure receive impulse response,
      signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) respectively, have
      been used for a quantitative comparison of imaging results. The measured
      fractional bandwidths of the CMUT arrays are larger compared to PZT probes.
      Moreover, both SNR and CNR are enhanced by at least 6 dB with CMUT technology.
      This work highlights the potential of CMUT technology for PA imaging through
      qualitative and quantitative parameters.

PMID- 29034169
TI  - Fluence compensation in raster-scan optoacoustic angiography.
AB  - Modern optical imaging techniques demonstrate significant potential for high
      resolution in vivo angiography. Optoacoustic angiography benefits from higher
      imaging depth as compared to pure optical modalities. However, strong attenuation
      of optoacoustic signal with depth provides serious challenges for adequate 3D
      vessel net mapping, and proper compensation for fluence distribution within
      biotissues is required. We report on the novel approach allowing to estimate
      effective in-depth fluence profiles for optoacoustic systems. Calculations are
      based on Monte Carlo simulation of light transport and account for complex
      illumination geometry and acoustic detection parameters. The developed fluence
      compensation algorithm was tested in in vivo angiography of human palm and
      allowed to overcome significant in-depth attenuation of probing radiation and
      enhance the contrast of lower dermis plexus while preserving high resolution of
      upper plexus imaging.

PMID- 29034170
TI  - Changes over time in population level transport satisfaction and mode of travel:
      A 13 year repeat cross-sectional study, UK.
AB  - AIM: The aim of the study was to examine changes over time in satisfaction with
      usual transport mode, explore individual and area level characteristics as
      mediators in the likelihood of transport satisfaction, and whether any changes in
      transport satisfaction varied by these factors over time. METHODS: Adults from
      West Central Scotland, United Kingdom, who participated at both waves of the
      repeat cross-sectional 'Transport, Health and Well-being Study' conducted in 1997
      (n=2735) and 2010 (n=2024) were assessed. Individuals completed a detailed postal
      questionnaire at both time points including self-rated satisfaction with usual
      transport mode (using a seven point scale subsequently dichotomised to a binary
      outcome of satisfied (1-2) and other (3-7)). Participants reported usual
      transport mode for travel to various destinations. A multilevel logistic
      regression model was used and individuals were nested within areas (c. 4000
      population). RESULTS: At the 2010 sweep, two thirds (n=1345) of individuals were
      satisfied with their transport choice. Those with fair/poor health were less
      satisfied with their usual transport compared to those in better health (Odds
      Ratio (OR) 0.49, p<0.001). Access to a car was associated with overall transport
      satisfaction (OR 2.63, p<0.001) and the effect of deprivation on transport
      satisfaction was mitigated when adjusted by household car access. Transport
      satisfaction increased more from 1997 to 2010 for retired individuals compared to
      those in employment (OR 1.40, p=0.032), and for those who travelled by public
      transport (OR 2.39, p=0.005) and using multiple modes (OR 2.19, p<0.001) compared
      to those who travelled by car. CONCLUSIONS: The proportion of those who travelled
      using public transport, active modes or by multiple mode increased journey
      satisfaction over time at a greater rate than those who travelled by car,
      highlighting that continued efforts should be made to promote these more active
      transport modes which have potential to impact on health.

PMID- 29034171
TI  - Does exposure to new transport infrastructure result in modal shifts? Patterns of
      change in commute mode choices in a four-year quasi-experimental cohort study.
AB  - BACKGROUND: Intervention studies suggest that changing the built environment may
      encourage a modal shift from car travel towards active travel. However, little is
      known about the detail of patterns of changes in travel behaviour. METHOD: Adult
      commuters working in Cambridge (UK) completed annual questionnaires between 2009
      and 2012. Commuting was assessed using a validated seven-day travel-to-work
      record. The intervention consisted of the opening of a guided busway with a path
      for walking and cycling in 2011. Exposure to the intervention was defined as the
      negative of the square root of the shortest road distance from home to the
      busway. We investigated the association between exposure to the intervention and
      specific modal shifts and patterns of change, along with individual mode choice
      patterns over the entire four-year period. RESULTS: Five groups of patterns of
      change were found in our in-depth explorations: (1) no change, (2) a full modal
      shift, (3) a partial modal shift, (4) non-stable but patterned behaviour, and (5)
      complicated or apparently random patterns. A minority of participants had a
      directed change of either a full modal shift or, more commonly, a partial modal
      shift, whereas a large proportion showed a highly variable pattern. No
      significant associations were found between exposure to the intervention and
      specific modal shifts or patterns of change. CONCLUSION: Our analyses revealed a
      large diversity in (changes in) travel behaviour patterns over time, and showed
      that the intervention did not result in one specific pattern of behaviour change
      or produce only full modal shifts. These insights are important for improving the
      measurement of travel behaviour, improving our understanding of how changes in
      travel behaviour patterns occur, and fully capturing the potential impacts of
      interventions.

PMID- 29034172
TI  - Health and greenhouse gas mitigation benefits of ambitious expansion of cycling,
      walking, and transit in California.
AB  - The purpose of this research was to quantify health co-benefits and carbon
      reductions of preferred scenarios of California regional transportation plans and
      alternatives with ambitious levels of active transport. The alternatives were
      designed to examine the efficacy of independent contributions of walking,
      bicycling, and transit at levels consistent with the U.S. Surgeon General
      recommendation for physical activity. Using data from travel and health surveys,
      vital statistics, collision databases, and outputs from regional and statewide
      travel models, the Integrated Transport and Health Impacts Model estimated the
      change in the population disease burden, as measured by deaths and disability
      adjusted life years (DALYs), due to a shift from a 2010 baseline travel pattern
      to an alternative. Health pathways modeled were physical activity and road
      traffic injuries. The preferred scenarios increased statewide active transport
      from 40.5 to 53.4 min person-1 w-1, which was associated with an annual decrease
      of 909 deaths and 16,089 DALYs. Sensitivity analyses that accounted for 2040
      projected age- and sex-specific population characteristics and cause-specific
      mortality rates did not appreciably alter the annual change in deaths and DALYs
      on a population basis. The ambitious, maximal alternatives increased population
      mean travel duration to 283 min person-1 w-1 for walking, bicycling, or transit
      and were associated a reduction in deaths and DALYs from 2.5 to 12 times greater
      than the California preferred scenarios. The alternative with the largest health
      impact was bicycling 283 min person-1 w-1 which led to 8,543 fewer annual deaths
      and 194,003 fewer DALYs, despite an increase in bicyclist injuries. With
      anticipated population growth, no alternative achieved decreases in carbon
      emissions but bicycling had the greatest potential for slowing their growth.
      Alternatives that included transit similarly reduced carbon emissions, but with
      less health benefit. Aggressive expansion of active transport is an efficacious,
      but underutilized policy option with significant health co-benefits for
      mitigating greenhouse gases.

PMID- 29034173
TI  - Mycobacteria Bovis osteomyelitis following intravesical BCG for bladder cancer.
AB  - Mycobacteria Bovis osteomyelitis is a rare adverse effect after Bacillus Calmette
      Guerin (BCG) intravesical therapy. A 62-year-old male presented with acute spinal
      cord compression three months after completing his second course of therapy for
      bladder cancer. The first course with intravesical BCG was complicated with an
      episode of hematuria. He reported intermittent subjective fever for 3 weeks
      thereafter which resolved with Tylenol. Interferon-alpha2 B was added to the
      second cycle of intravesical BCG with the indication here being residual tumor,
      and was tolerated well. His complete blood count and liver function tests were
      unremarkable on admission. MRI showed features of osteomyelitis with cord
      compression at T4/T5. Biopsy of the affected bone showed caseating granuloma
      which was positive for acid fact bacilli, later confirmed to be Mycobacterium
      Bovis by PCR and pyrazinamide resistance. He was started on intravenous steroids
      and underwent spinal cord decompression. Rifampin, Isoniazid, and Ethambutol were
      then commenced. His weakness improved and after two months of therapy he was
      asymptomatic and back to his baseline function. Osteomyelitis is a rare but
      serious complication. Early diagnosis and treatment is important as the outcomes
      are good.

PMID- 29034174
TI  - Rare case of Rhizobium radiobacter bioprosthetic mitral valve endocarditis.
AB  - Rhizobium radiobacter is an aerobic, gram negative, rod-shaped, bacterium
      typically found in the soil. Commonly a plant pathogen, it is also a rare human
      pathogen causing serious disease. Risk factors for infection include neutropenia,
      leukopenia, catheters, hospitalization, and low CD4+ lymphocyte count, especially
      in patients with malignancy or human immunodeficiency virus. There is currently
      limited literature to establish a definitive guideline for antimicrobial therapy
      and obtaining susceptibilities from a specialized laboratory is appropriate. We
      present a successfully treated case of R. radiobacter bioprosthetic mitral valve
      endocarditis in a patient with previous S. epidermidis endocarditis.

PMID- 29034175
TI  - Refining low protein modular feeds for children on low protein tube feeds with
      organic acidaemias.
AB  - : Children with inherited metabolic disorders (IMD) who are dependent on tube
      feeding and require a protein restriction are commonly fed by 'modular tube
      feeds' consisting of several ingredients. A longitudinal, prospective two-phase
      study, conducted over 18 months assessed the long-term efficacy of a pre-measured
      protein-free composite feed. This was specifically designed to meet the non
      protein nutritional requirements of children (aged over 1 year) with organic
      acidaemias on low protein enteral feeds and to be used as a supplement with an
      enteral feeding protein source. METHODOLOGY: All non-protein individual feed
      ingredients were replaced with one protein-free composite feed supplying fat,
      carbohydrate, and micronutrients. Thirteen subjects, median age 7.4y (3-15.5y),
      all nutritionally tube dependent (supplying nutritional intake: >= 90%, n = 12;
      75%, n = 1), and diagnosed with organic acidaemias (Propionic acidaemia, n = 6;
      Vitamin B12 non-responsive methyl malonic acidaemia, n = 4; Isovaleric acidaemia,
      n = 2; Glutaric aciduria type1, n = 1); were studied. Nutritional intake,
      biochemistry and anthropometry were monitored at week - 8, 0, 12, 26 and 79.
      RESULTS: Energy intake remained unchanged, providing 76% of estimated energy
      requirements. Dietary intakes of vitamins, minerals and essential fatty acids
      significantly increased from week 0 to week 79, but sodium, potassium, magnesium,
      decosahexanoic acid and fibre did not meet suggested requirements. Plasma zinc,
      selenium, haemoglobin and MCV significantly improved, and growth remained
      satisfactory. Natural protein intake met WHO/FAO/UNU 2007 recommendations.
      CONCLUSIONS: A protein-free composite feed formulated to meet the non-protein
      nutritional requirements of children aged over 1 year improved nutritional
      intake, biochemical nutritional status, and simplified enteral tube feeding
      regimens in children with organic acidaemias.

PMID- 29034176
TI  - Imaging tumour thrombus of clear cell renal cell carcinoma: FDG PET or PSMA PET?
      Direct in vivo comparison of two technologies.

PMID- 29034177
TI  - Rapid recurrence and radiographic progression of sarcomatoid renal cell
      carcinoma.
AB  - Sarcomatoid renal cell carcinoma (sRCC) is an aggressive variant of renal cell
      carcinoma (RCC) that has a significantly lower overall survival. Even after
      prompt surgical extirpation, this histologic variant progresses rapidly. We
      present a case of an early recurrence and rapid progression of sRCC despite
      successful radical resection.

PMID- 29034178
TI  - Retroperitoneal fibrosis associated with IgG4-related disease diagnosed by
      prostate biopsy developed with acute post-renal renal failure: A case report.

PMID- 29034179
TI  - Case of an Airsoft pellet induced epididymal laceration and secondary testicular
      torsion with the loss of affected testis.

PMID- 29034180
TI  - Significance of fermentation process on biochemical properties of Phaseolus
      vulgaris (red beans).
AB  - Phaseolus vulgaris L. beans have been characterized as a nearly perfect food in
      all around the world. It is consider functional in terms of providing nutrients
      and energy to sustain daily life. Red bean contain high protein, mineral, fibres
      and chemically diverse micronutrient composition, which can be affected by
      processing. The main aim of this work is to investigate the effect of open and
      controlled fermentation on the proximate composition, mineral elements,
      antinutritional factors and flatulence- causing oligosaccharides of a
      domesticated bean (Anger, conscope and Loko). Open fermentation was done using
      endogenous microorganism present in the seed of beans, while controlled
      fermentation was done on autoclaved beans flour inoculated with thermophilic
      lactic culture which is a mixed strain culture containing Lactobacillus
      acidophilus, Bifidobacterium and Streptococcus thermophillus. The result shows
      that the open and controlled fermentation increased the protein digestibility up
      to 90% in all samples and 4 days of fermentation time, loko red bean was found to
      more suitable. The chemical compositions and mineral contain was also high as
      compared to remaining two verities.

PMID- 29034181
TI  - Inhibitory effect of yokukansan on the decrease in the hippocampal excitatory
      amino acid transporter EAAT2 in stress-maladaptive mice.
AB  - Chronic stress is widely recognized as a risk factor for the development of major
      depression and anxiety disorders. Recently, we reported that yokukansan (YKS), a
      traditional Japanese herbal medicine, alleviated emotional abnormality in stress
      maladaptive mice. The aim of the present study was to examine the effect of YKS
      on the expression of excitatory amino acid transporter (EAAT) 1-4 in the
      prefrontal cortex and hippocampus in stress-maladaptive mice. Mice were
      chronically exposed to inadaptable stress, i.e. repeated restraint stress for 240
      min/day for 14 days. After the final exposure to stress, brains of mice were
      rapidly removed and the hippocampus and prefrontal cortex were dissected.
      Expressions of EAAT1-4 and glial fibrillary acidic protein (GFAP), a marker of
      astrocytes, in the brain tissues were analyzed by western blotting. Western blot
      analysis revealed that the expression level of EAAT2 was specifically decreased
      in the hippocampus of stress-maladaptive mice while there were no changes in the
      level of GFAP, and this change was inhibited by chronic treatment with YKS. In
      contrast, no changes were observed in the levels of EAAT1, EAAT3 or EAAT4 in
      stress-maladaptive mice. These results suggest that YKS may protect against the
      decrease in hippocampal EAAT2 expression induced by stress maladaptation, and
      this may contribute, at least in part, to the improvement of emotional
      abnormality.

PMID- 29034183
TI  - Alzheimer Disease: Clues from traditional and complementary medicine.
AB  - Despite modern medicine's incredible innovation and resulting accumulation of
      valuable knowledge, many of the world's most problematic diseases such as
      Alzheimer Disease (AD) still lack effective cures and treatments. Western
      medicine has revealed many genetic, cellular, and molecular processes that
      characterize AD such as protein aggregation and inflammation. As the need for
      novel and effective treatments increases, researchers have turned towards
      traditional medicine as a resource. Modern, evidence based research examining
      traditional and complementary remedies for AD has generated promising results
      within the last decade. Animal based products inhibiting cellular toxicity, anti
      inflammatory nutraceuticals such as omega-3 fatty acids, and plant based
      compounds derived from herbal medicine demonstrate viability as neuroprotective
      treatments and possible application in developing pharmaceuticals. Analysis of
      antioxidant, anti-inflammatory, and neuroprotective phytochemicals used in
      various traditional medicines around the world reveal potential to ameliorate and
      prevent the devastating neurodegeneration observed in AD.

PMID- 29034182
TI  - Food strategies of renal atrophy based on Avicenna and conventional medicine.
AB  - Kidneys have an important role in the body. Any damage to kidney role can damage
      many organs of the body. Traditional Persian Medicine (TPM) or Iranian
      traditional medicine (ITM) is an ancient temperamental medicine with many
      literatures about kidney diseases and Avicenna (980-1025 AD) describes kidney
      diseases in details. This is a review study by searching of the most important
      clinical and pharmaceutical TPM textbooks such as The Canon of Medicine by
      Avicenna and scientific data banks using keywords such as "Hozal-e-Kolye", renal
      atrophy, tubular atrophy, kidney, chronic kidney disease, and end stage renal
      disease. This paper found that "Hozal-e-Kolye" in TPM texts is the same tubular
      atrophy in conventional medicine due to some similar symptoms between them.
      Lifestyle modification and use of proposed foodstuffs can be considered as a
      complementary medicine in addition to conventional treatments to manage these
      patients. TPM scholars prescribed some foodstuffs such as camel milk, sheep's
      milk and Ficus carica for this disease as a complementary management. This study
      aimed to explain HK (the same tubular atrophy considering their similar symptoms)
      and introduce some foodstuffs. It seems using of foodstuffs affecting tubular
      atrophy based on TPM literatures can has a role as a supplemental method in
      company with conventional medicine management.

PMID- 29034184
TI  - Understanding nutrition and immunity in disease management.
AB  - As we search for answers to modern medicine's most prevalent and challenging
      problems, the relationship between nutrition, immunity, and biological function
      of various natural compounds are preimminent. Nutritional research involving
      genomics provides rational capabilities for preventing disease. Scientific
      advances in genomic sequencing reveal opportunities for exploring diet-health
      relationships and potential for individual, genotype based dietary
      recommendations. Utilizing molecular and genetic technology to analyze impact of
      nutrition on genomics and metabolism reveals that nutrients may influence certain
      innate and/or acquired immune functions. By analyzing immune mechanisms including
      their cells and complex molecules, animal models have offered relevant insight
      that clarifies interrelations between immunity and nutrition. Plant products also
      provide numerous resources through bioengineering for designing novel
      pharmaceuticals. Having long been employed successfully in traditional and folk
      medicines, plant compounds exhibit anti-inflammatory, antimicrobial, and
      angiogenic activity. As a result, we now have a promising arsenal for successful
      application of bioactive compounds.

PMID- 29034185
TI  - Ashtawarga plants - Suffering a triple standardization syndrome.
AB  - Ayurveda is one of the oldest known holistic health care systems recommending
      diverse medicinal uses of plants for prevention and cure of diseases and illness.
      World Health Organization (WHO) estimates that the holistic system is gaining
      more popularity due to its easy availability, low cost, congeniality, better
      accessibility and higher safety than allopathic medicine. Demand of herbal drugs
      is increasing day-by-day because of increasing popularity of herbal drugs;
      however market fails to meet this supply due to numerous factors, one of the
      important factors being the extinction of these plants from local flora. About
      560 herbal species of India have been included in the Red List of Threatened
      species. Hence to overcome problem of non-availability of endangered species,
      Department of AYUSH, Govt. of India has permitted the substitution of rare herbal
      drugs with available substitutes on the basis of Ayurvedic concepts. Due to this,
      herbal drug industry has started exploiting the situation and now Ayurvedic
      products are suffering from a serious problem of adulteration with addition of
      spoiled, inferior, spurious drugs that are inferior in therapeutic/chemical
      properties and used to enhance profits. Adulteration with other plants degrades
      the quality and credibility of Ayurvedic medicine. Ashtawarga plants being an
      important part of many Ayurvedic formulations are also available in a very
      limited amount and likely to be substituted by cheap adulterants. Keeping in view
      the above situation, a metadata analysis has been conducted to find out types of
      adulteration/substitutions malpractices going on for Ashtawarga plants.

PMID- 29034186
TI  - Medicinal, biological and phytochemical properties of Gentiana species.
AB  - Gentiana, a cosmopolitan and important genus of the Gentianaceae family,
      comprises 400 species distributed among the world. Based on the studies of
      Iranian traditional medicine texts, there are some promising bioactivities for
      this genus that is unknown in modern medicine and some of them are still the
      basis of new remedies. In traditional medicine texts, Gentiana's different
      exclusive forms of preparations are effective for treatment of some disorders
      such as menstrual over-bleeding, conjunctivitis, vitiligo, animals venom
      poisoning, injuries, infected wounds, pain and swelling of liver, spleen, stomach
      and sprains of muscles. There are some activities that are the same in
      traditional and modern medicine such as anti-inflammatory, hepatoprotective and
      diuretic effects. Phytochemical investigations on the title genus have led to
      characterization many secondary metabolites. Secoiridoidal and iridoid glycosides
      such as gentiopicroside, xanthones, monoterpene alkaloid; polyphenol and flavones
      are the constituents that have been shown the pharmacological activities in
      different gentian species. This article studies the Gentiana according to the
      Iranian traditional and modern medicine.

PMID- 29034187
TI  - Electrical nerve stimulation for xerostomia: A meta-analysis of randomised
      controlled trials.
AB  - BACKGROUND: Xerostomia leads to caries, infection and overall psychological
      discomfort. Salivary substitutes and pharmacological agents have been tried only
      with temporary relief. The use of transcutaneous electrical nerve stimulation
      (TENS) has been contemplated on by various researchers for treatment of
      xerostomia. We carried out the present review as a systematic compilation and
      quantitative synthesis of the existing evidence related to the utility of TENS in
      patients with xerostomia. METHODOLOGY: Six randomized controlled trials were
      identified from databases for inclusion and analysed using non-Cochrane mode in
      RevMan 5.0 software. The heterogeneity between the studies were assessed using
      Forest plot, I2 statistics wherein more than 50% was considered to have moderate
      to severe heterogeneity and Chi-square test with a statistical P-value of less
      than 0.10 to indicate statistical significance. RESULTS: Results show that the
      effect of TENS on salivary flow rate in 369 participants with SMD [95% CI] was
      0.63 [-0.03, 1.29] and was not statistically significant. CONCLUSION: To
      conclude, the current evidence does not support the use of TENS in patients with
      xerostomia and may be considered as a salivary substitute for symptomatic
      improvement. However the type, frequency and amplitude of current used needs to
      be studied in detail. High quality randomized controlled trials with adequate
      power are required, either to support or refute the use of TENS in xerostomia.

PMID- 29034188
TI  - Validation of therapeutic anti-inflammatory potential of Arjuna Ksheera Paka - A
      traditional Ayurvedic formulation of Terminalia arjuna.
AB  - Arjuna Ksheera Paka (AKP), a traditional Ayurvedic formulation of Terminalia
      arjuna (T. arjuna) bark powder is used for its cardioprotective effects. However,
      its anti-inflammatory efficacy remained unexplored. In the present study, AKP was
      prepared in cow milk (as per standard Ayurvedic procedure) and compared with
      standard hydroalcoholic extract (HA) of T. arjuna. The extracts were analyzed for
      gross phytoconstituents levels, and their antioxidant activity was assayed by
      DPPH free radical scavenging activity and inhibition of lipid peroxidation. The
      in vivo anti-inflammatory activity of AKP and HA was studied in carrageenan
      induced hind paw biphasic edema in C57BL/6 mice (at 200, 400 and 800 mg/kg BW).
      The percentage extraction yield of AKP was two folds higher than HA implying that
      the phytoconstituents in AKP were diluted by a factor of 0.5. The total
      polyphenol content of HA was (3.8 times) higher than AKP and the antioxidant
      activity of HA was also higher compared to AKP. Both the extracts, however,
      showed significant (p < 0.05) anti-inflammatory activity in reducing paw edema in
      mice. The efficacy of HA was more than AKP at early phase of inflammation,
      whereas, in the late phase of inflammation AKP was more efficacious and
      equipotent to HA. Thus, regardless of low in vitro antioxidant activity, AKP
      exhibited potential in vivo anti-inflammatory activity. The higher efficacy of
      AKP could be due to the presence of milk solids. These milk solids may act as
      adjuvants to T. arjuna's phytoconstituents, contributing to their sustained
      bioavailability, leading to higher in vivo anti-inflammatory efficacy at lower
      drug concentrations.

PMID- 29034189
TI  - Antidiabetic activity of extracts of Anacardium occidentale Linn. leaves on n
      streptozotocin diabetic rats.
AB  - Anacardium occidentale L. (Anacardiaceae) is used in South Cameroon as well as in
      other tropical countries by traditional practitioners as a folk remedy for
      treatment of diabetes mellitus. We demonstrated the antidiabetic potential of the
      plant extracts in n-streptozotocin diabetic rats. The aim of the current study
      was to investigate the antidiabetic effects of ethanol extract of leaves of A.
      occidentale on neonatal streptozotocin diabetic rats. Two day old neonates were
      injected with 100 mg/kg of streptozotocin. At the end of the experimental period
      of 30 days, reduction in the fasting blood glucose levels, serum insulin,
      glycated hemoglobin levels, serum lipid parameters, and renal function biomarkers
      were estimated in the control and treated rats. Histopathological examination of
      liver, kidney and pancreas were also carried out. On administration of 100 mg/kg
      of plant extract, blood glucose levels of the rats showed 8.01% and 19.25%
      decrease in the fasting blood glucose levels on day 15 and day 30, respectively.
      The administration of extract showed that the effects of extract treatment are
      comparable to treatment with the standard drug Pioglitazone. These results
      demonstrate significant antidiabetic potential of the ethanol extract of leaves
      of A. occidentale, justifying the use of plant in the indigenous system of
      medicine. Further studies for investigating the specific compound(s) responsible
      for such beneficial role in diabetes would open new outlook in the therapy of
      type 2 diabetes.

PMID- 29034190
TI  - Antiasthmatic related properties of Abrus precatorius leaves on various models.
AB  - OBJECTIVE: Asthma is a multifaceted inflammatory disorder which results into
      narrowing of airway with broncho-constriction and spasm. As the complex
      pathophysilogy of asthma, various animal models are generally used to investigate
      the immunological and physiological pathogenesis of disease. Abrus precatorius
      Linn (Fabacease) is a climbing shrub. The leaves and roots are sweet in taste and
      traditionally used for the treatment of asthma, bronchititis, and inflammation.
      A. precatorius possesses different pharmacological activities. Hence the
      objective of this study was to evaluate antiasthmatic activity of ethanol extract
      of A. precatorius leaves using various models. METHODS: In present study ethanol
      extract of A. precatorius leaves was evaluated for antiasthmatic activity using
      carrageenan induced paw edema in rats [100-150 mg/kg], histamine induced
      bronchospasm in guinea pig [200-400 mg/kg] and histamine induced contraction of
      goat tracheal chain [2.5-25 MUg/ml]. RESULTS: Result of study revealed that
      ethanol extract of A. precatorius significantly exhibited anti-inflammatory
      effects in rats, oral treatment of extract on guinea pig significantly increases
      histamine induced preconvulsive dysponea times and the ethanol extract of plant
      increases got tracheal chain precontracted with histamine. CONCLUSION: Hence
      present study concludes that ethanol extract of A. precatorius possesses
      antiasthmatic activity.

PMID- 29034191
TI  - Pharmacological properties of Salvia officinalis and its components.
AB  - Salvia officinalis (Sage) is a plant in the family of Labiatae/Lamiaceae. It is
      native to Middle East and Mediterranean areas, but today has been naturalized
      throughout the world. In folk medicine, S. officinalis has been used for the
      treatment of different kinds of disorders including seizure, ulcers, gout,
      rheumatism, inflammation, dizziness, tremor, paralysis, diarrhea, and
      hyperglycemia. In recent years, this plant has been a subject of intensive
      studies to document its traditional use and to find new biological effects. These
      studies have revealed a wide range of pharmacological activities for S.
      officinalis. Present review highlights the up-to-date information on the
      pharmacological findings that have been frequently reported for S. officinalis.
      These findings include anticancer, anti-inflammatory, antinociceptive,
      antioxidant, antimicrobial, antimutagenic, antidementia, hypoglycemic, and
      hypolipidemic effects. Also, chemical constituents responsible for
      pharmacological effects of S. officinalis and the clinical studies on this plant
      are presented and discussed.

PMID- 29034192
TI  - Evaluation of analgesic and anti-inflammatory activity of Bridelia retusa
      (Spreng) bark.
AB  - Several species of Bridelia have been used in the condition of pain & arthritis
      in Indian folk medicine. Present study revealed the preliminary phytochemical
      investigation and evaluation of analgesic, anti-inflammatory and anti-arthritic
      activity as well as underlying mechanism of bark of Bridelia retusa Spreng.
      (Euphorbiaceae). The bark was subjected to extraction using pet.ether, ethyl
      acetate and acetone. All the extracts were significantly inhibit abdominal
      writhings response and licking time in late phase of formalin test. Extracts
      could also significantly inhibit mean paw edema of rats induced by carrageenan &
      histamine at dose of 200 & 400 mg/kg, i.p. Test materials also showed significant
      dose dependent reduction in cotton pellet granuloma & acetic acid induced
      vascular permeability at 400 mg/kg. Oral administration of B. retusa fractions in
      CFA induced arthritic rats, physical, biochemical and hematological parameters
      observed in arthritic animals were altered significantly to near normal
      condition. The maximum paw edema inhibition at day 21 was observed at 400 mg/kg.
      It also proved significant protection against protein denaturation & RBC membrane
      damage. The GC-MS analysis of EA extract revealed the presence of beta
      sitosterol, stigmasterol, lupeol and friedelin (Pentacyclic triterpenoid).
      Therefore present study has demonstrated the analgesic; anti-inflammatory and
      anti-arthritic activities of B. retusa bark and suggested that the molecular
      membrane might be associated with inhibition of biochemical and hematological
      parameters. Overall bioactive profile of B. retusa used phytomedicine in future
      for inflammatory conditions.

PMID- 29034194
TI  - Evidence based study of antidiabetic potential of C. maxima seeds - In vivo.
AB  - OBJECTIVE: In vitro antidiabetic efficacy of Cucurbita maxima seed extract (CMSE)
      has already been studied in our previous findings. Thus, in order to validate
      these findings in biological system, in vivo antidiabetic activity of aqueous
      extract was investigated in normal as well as diabetic experimental models.
      METHODS: Variable doses of extract were administered orally to normal and STZ
      induced mild diabetic rats during fasting blood glucose (FBG) and glucose
      tolerance test (GTT) studies. In order to determine the extract's antidiabetic
      potential long-term FBG and post prandial glucose (PPG) studies were also carried
      out. RESULTS: Most effective dose of 200 mg kg-1 of CMSE decreases the blood
      glucose level (BGL) in normal rats by 29.02% at 6 h during FBG studies and 23.23%
      at 3 h during GTT. However, the maximum reduction observed in BGL of mild
      diabetic rats during GTT the same interval of time was 26.15%. Moreover, in case
      of severely diabetic rats a significant reduction of 39.33% was observed in FBG
      levels whereas, in case of positive control, rats treated with 2.5 mg kg-1 of
      glipizide, a fall of 42.9% in FBG levels was observed after 28 days. Results of
      PPG level also showed a fall of 33.20% in severely diabetic rats as compared to
      the positive control showing a fall of 44.2% at the end of the 28 days.
      CONCLUSION: Thus, the present study validate the hypoglycemic and antidiabetic
      effect of CMSE and hence this extract could be explored further for developing as
      a novel antidiabetic agent.

PMID- 29034193
TI  - Comparative study of herbal plants on the phenolic and flavonoid content,
      antioxidant activities and toxicity on cells and zebrafish embryo.
AB  - Natural antioxidants derived from plants have shown a tremendous inhibitory
      effect on free radicals in actively metabolizing cells. Overproduction of free
      radicals increases the risk factor of chronic diseases associated with diabetes,
      cancer, arthritis and cardiovascular disease. Andrographis paniculata, Cinnamon
      zeylanicum, Curcuma xanthorrhiza, Eugenia polyantha and Orthosiphon stamineus are
      ethnomedicinal plants used in the Asian region to treat various illnesses from a
      common fever to metabolic disease. In this study, we have quantified the total
      phenolic (TPC) and flavonoid content (TFC) in these plants and its inhibitory
      effect on 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radicals as well as the
      cytotoxicity effect on cell lines proliferation and zebrafish embryogenesis.
      Results showed that Cinnamon zeylanicum and E. polyantha have the highest
      phenolic and flavonoid content. Furthermore, both herbs significantly inhibited
      the formation of DPPH and ABTS free radicals. Meanwhile, O. stamineus exhibited
      minimum cytotoxicity and embryotoxicity on tested models. Good correlation
      between IC50 of 3T3-L1 cells and LC50 embyrotoxicity was also found. This study
      revealed the potent activity of antioxidant against free radical and the
      toxicology levels of the tested herbal plants.

PMID- 29034195
TI  - Protective effect of hydro-alcoholic extract of Salvia haematodes Wall root on
      cognitive functions in scopolamine-induced amnesia in rats.
AB  - Diminished cholinergic transmission may be responsible for development of
      amnesia. Hence, the present study was undertaken to investigate the possible
      protective effect of hydro-alcoholic extract of Salvia haematodes Wall root
      (HESH) on cognitive functions in scopolamine-induced amnesia in adult Sprague
      Dawley rats. The rats were divided randomly into five groups each consisting of
      five rats (n = 5). Rats of the groups I, II, III, IV, and V received orally
      normal saline (10 ml/kg b. wt.), normal saline (10 ml/kg), standard drug
      rivastigmine (1.5 mg/kg), HESH (20 mg/kg), and HESH (40 mg/kg), respectively once
      a day for fourteen days. Then, they were subjected to single dose of scopolamine
      (1 mg/kg b. wt. ip) except in group I on fourteenth day 60 min after respective
      normal saline or drug administration. They were observed for the effects on step
      down latency (SDL), locomotor activity and brain AChE activity for the learning
      and memory. The acquisition SDL, retention SDL and locomotor activity were
      significantly (p < 0.01) decreased while AChE activity was significantly (p <
      0.01) increased in scopolamine-treated group II as compared to normal control
      group I. The acquisition SDL, retention SDL and locomotor activity were
      significantly (p < 0.01) increased while, AChE activity was significantly (p <
      0.01) decreased with all the doses of HESH and in rivastigmine-treated group as
      compared to scopolamine-treated group II. Hydro-alcoholic extract of S haematodes
      root possesses protective effect on cognitive functions and may prove to be a
      useful memory restorative agent in the management of cognitive dysfunctions as in
      amnesia and Alzheimer's diseases.

PMID- 29034197
TI  - Characterization of Calcined Jade and its immunomodulatory effect on macrophage
      isolated from Swiss albino mice.
AB  - Calcined Jade (CJ) is a metasilicate frequently used in traditional system of
      medicine as tonic to vital organs with several other pharmacological activities.
      X-ray powder diffraction (XRPD), inductively coupled plasma mass spectrometry
      (ICP-MS), atomic absorption spectroscopy (AAS) and CHNS analyzer techniques were
      used to characterize CJ sample. CJ was administered orally to Swiss albino mice
      at a dose of 50, 75, 100 and 200 MUg/kg body weight for 10 days and modulation of
      the macrophage mediated innate immune responses was studied. Flow cytometric
      analysis of TLR-2/4 on peritoneal macrophage revealed elevated expression of TLR
      2 as compared to control. Significant increase in phagocytic activity was
      observed in peritoneal macrophage. The lymphoid organs weight and other toxicity
      parameters did not exhibit any harmful effect. To evaluate the presence of
      nanoparticles, CJ was dissolved in milli Q water, filtered and lyophilized.
      Transmission electron microscopic (TEM) analysis revealed the presence of
      spherical nanoparticles in CJ [14.7-142.0 nm dimension with average particle size
      of 64.6 nm]. In conclusion, we report stimulation of innate immune responses by
      CJ may partly be due to the formation of nanoparticles. Further experiments using
      isolated nanoparticles may further validate the role of nanoparticles.

PMID- 29034196
TI  - Protective effect of ethyl acetate fraction of Biophytum sensitivum extract
      against sodium oxalate-induced urolithiasis in rats.
AB  - The methanolic whole plant extract of Biophytum sensitivum (ganying cao) has been
      found to possess antiurolithiatic effect. The present study was undertaken to
      evaluate the antiurolithiatic effect of some fractions of methanolic whole plant
      extract of B. sensitivum (MBS) in rats as a step toward activity-directed
      isolation of antiurolithiatic component. The MBS was successively extracted with
      dichloromethane, ethyl acetate, ethanol and water to obtain fractions. Sodium
      oxalate (70 mg/kg, i.p.) was administered to rats for seven days to develop
      calcium oxalate urolithiasis. These rats were treated with two doses (20 and 40
      mg/kg, p.o.) of the fractions, 1 h before sodium oxalate injections.
      Antiurolithiatic activity was assessed by estimating biochemical changes in
      urine, serum and kidney homogenate along with histological changes in kidney
      tissue. Sodium oxalate administration caused biochemical alterations in urine
      which was found to be prevented significantly by the ethyl acetate fraction.
      Supplementation with ethyl acetate fraction prevented the elevation of serum
      creatinine, uric acid and blood urea nitrogen levels. The elevated calcium,
      oxalate and phosphate levels in the kidney tissue homogenate of lithiatic rats
      were significantly reduced by the treatment with ethyl acetate fraction. The
      ethyl acetate fraction also caused significant decrease in lipid peroxidation
      activity, accumulation of calcium oxalate deposits and histological changes in
      the kidney tissue. The results showed that the antiurolithiatic component of the
      methanolic whole plant extract of the plant is contained in the ethyl acetate
      fraction. The effect is attributed to its diuretic, antioxidant, nephroprotective
      properties and effect on lowering the concentration of urinary stone-forming
      constituents.

PMID- 29034198
TI  - Phenolic constituents and modulatory effects of Raffia palm leaf (Raphia hookeri)
      extract on carbohydrate hydrolyzing enzymes linked to type-2 diabetes.
AB  - This study sought to investigate the effects of Raffia palm (Raphia hookeri) leaf
      extract on enzymes linked to type-2 diabetes mellitus (T2DM) and pro-oxidant
      induced oxidative stress in rat pancreas. The extract was prepared and its alpha
      amylase and alpha-glucosidase inhibitory effects were determined. Radical [2,2
      diphenyl-1-picrylhydrazyl (DPPH)] scavenging and Fe2+-chelating abilities, and
      inhibition of Fe2+-induced lipid peroxidation in rat pancreas homogenate were
      assessed. Furthermore, total phenol and flavonoid contents, reducing property,
      and high performance liquid chromatography diode array detector (HPLC-DAD)
      fingerprint of the extract were also determined. Our results revealed that the
      extract inhibited alpha-amylase (IC50 = 110.4 MUg/mL) and alpha-glucosidase (IC50
      = 99.96 MUg/mL) activities in concentration dependent manners which were lower to
      the effect of acarbose (amylase: IC50 = 18.30 MUg/mL; glucosidase: IC50 = 20.31
      MUg/mL). The extract also scavenged DPPH radical, chelated Fe2+ and inhibited
      Fe2+-induced lipid peroxidation in rat pancreas all in concentration dependent
      manners with IC50 values of 402.9 MUg/mL, 108.9 MUg/mL and 367.0 MUg/mL
      respectively. The total phenol and flavonoid contents were 39.73 mg GAE/g and
      21.88 mg QAE/g respectively, while the reducing property was 25.62 mg AAE/g. The
      HPLC analysis revealed the presence of chlorogenic acid (4.17 mg/g) and rutin
      (5.11 mg/g) as the major phenolic compounds in the extract. Therefore, the
      ability of the extract to inhibit carbohydrate hydrolyzing enzymes and protect
      against pancreatic oxidative damage may be an important mechanisms supporting its
      antidiabetic properties and could make Raffia palm leaf useful in
      complementary/alternative therapy for management of T2DM. However, further
      studies such as in vivo should be carried out.

PMID- 29034201
TI  - Evaluation of Zanthoxylum armatum Roxb for in vitro biological activities.
AB  - Zanthoxylum armatum fruits are used traditionally as a spice in various food
      preparations. The aim of this study was analysis of antimicrobial, cytotoxic,
      phytotoxic, insecticidal, and anti-leishmanial activity. The crude extract showed
      86 +/- 10% antifungal activity (Agar tube dilution method) against Trichophyton
      longifusis while n-hexane, chloroform, and aqueous-methanol fractions inhibited
      this pathogen by 90 +/- 7, 85 +/- 10 and 70 +/- 9% respectively. The n-hexane and
      aqueous-methanol fraction also, respectively, showed 40 +/- 10 and 87 +/- 9%
      inhibition of Microsporum canis. Chloroform fraction also displayed antifungal
      activity against Aspergillus flavus (60 +/- 10%) and aqueous-methanol fraction
      against F. solani (40 +/- 8%). The crude ethanolic extract and its chloroform and
      aqueous-methanol fraction exhibited significant toxicity (Brine shrimps lethality
      assay) against brine shrimps having LC50 value of 6.66 +/- 1.1, 21.4 +/- 3.3 and
      29.6 +/- 3.9 MUg/ml, respectively. The crude ethanolic extract and its n-hexane
      soluble portion exhibited good anti-leishmanial activity (well serial dilution
      method) each having IC50 values of 50 +/- 5 MUg/ml. The crude extract and various
      fractions possessed excellent herbicidal activity (Lemna minor assay), and caused
      more than 90% inhibition of the plant growth at 1000 MUg/mL. The ethanolic
      extract, n-hexane and chloroform soluble portions caused 90% mortality in
      insecticidal activity (direct contact method) of Rhyzopertha dominica. The
      ethanolic extract and its n-hexane soluble portion, respectively, caused 80 and
      90% mortality of Callosobruchus analis. The present study showed that the tested
      fruit extracts of Z. armatum exhibited strong antifungal, cytotoxic, phytotoxic,
      insecticidal, and anti-leishmanial effects.

PMID- 29034199
TI  - Cardioprotective effects of Achillea wilhelmsii on the isolated rat heart in
      ischemia-reperfusion.
AB  - CONTEXT: There are some reports about protective effects of Achillea on the
      heart. OBJECTIVE: We investigated the effect of Achillea wilhelmsii extract on
      cardiac function during ischemia-reperfusion (I/R) injury in the isolated rat
      heart. MATERIALS AND METHODS: 60 male Wistar rats were randomly divided into 6
      groups; 1: Control group, 2: Control-ischemia (CI) 3: vitamin C (10 mg/kg), 4-6:
      Extract groups (E 100, E 200 and E 400 mg/kg). The animals received normal
      saline, vitamin C or A. wilhelmsii extract orally for 4 weeks. At the end of the
      treatment, the hearts were subjected to in vitro I/R Injury (20 min of global
      ischemia, followed by 40 min of reperfusion, Langendorff's mode). Heart rate (HR)
      and left ventricular pressure (LVP) were measured using a pressure transducer
      connected to a data acquisition system. Lactate dehydrogenase (LDH) and creatine
      kinase (CK) activities in the effluent were measured to determine the myocardial
      injury degree. The malondialdehyde (MDA), total thiol groups (-SH), superoxide
      anion dismutase (SOD) and catalase (CAT) in myocardial tissue were detected to
      determine the oxidative stress degree. RESULTS: Pretreatment with Achillea
      wilhlemsii significantly decreased the LDH, CK activities, and MDA level, while
      it increased the LVDP, +/-dp/dtmax, rate-pressure product (RPP), SH groups, SOD
      and CAT activities, and also the coronary artery flow. DISCUSSION AND CONCLUSION:
      Our findings indicated that Achillea wilhelmsii could provide protection for
      heart against the I/R injury which may be related to the improvement of
      myocardial oxidative stress states.

PMID- 29034200
TI  - Promising effect of Rosa damascena extract on high-fat diet-induced nonalcoholic
      fatty liver.
AB  - NAFLD is a chronic liver disease that affects a high proportion of the world's
      population which causes metabolic and hepatic damages. Rosa damascena Mill is
      traditionally used as a dietary supplement for liver disorders. This study was
      carried out to determine the beneficial effect of standardized extract of R.
      damascena on animal model of nonalcoholic fatty liver disease (NAFLD). NAFLD was
      induced by high-fat diet (HFD) in Wistar rats. HFD rats showed an increase (p <
      0.05) in the plasma lipid levels of total cholesterol (TC), triglyceride (TG),
      low-density lipoprotein (LDL), and reduced the high-density lipoprotein (HDL)
      levels. R. damascena significantly reduced the elevation of final body weight,
      liver fat accumulation, TG, TC, LDL-C concentrations and hepatic enzymes (p <
      0.05). Histopathological examination of hepatic tissue confirmed the therapeutic
      effect of R. damascena. Improvement of total antioxidant power activity, total
      thiol content, MPO enzyme activity, and also lipid peroxidation were also
      considered in treated animals (p < 0.05). HPLC analysis showed that phenolic
      compounds including gallic acid, quercetin and syringic acid are the main
      bioactive compounds of R. damascena hydroalcoholic extract. In conclusion, R.
      damascena dietary supplementation has a therapeutic effect in NAFLD. Improvement
      of oxidative stress associated damage in liver tissue is among the main
      pharmacological mechanisms involved in therapeutic activity of the plant.

PMID- 29034203
TI  - Immediate effect of bitter gourd, ash gourd, Knol-khol juices on blood sugar
      levels of patients with type 2 diabetes mellitus: A pilot study.
AB  - AIM: The aim of this study was to investigate the immediate effect of bitter
      gourd, Knol-khol, and ash gourd juices on blood glucose level among Type II
      diabetes mellitus patients. METHODS: In 2015, pilot study was conducted randomly
      enrolling 30 patients with type 2 diabetes mellitus into three groups in SRK
      college, India. The first group received bitter gourd juice at FBS range between
      120 to 300 mg per dl. The second, third group received Knol-khol, ash gourd juice
      respectively in the same range of fasting blood sugar level. Blood sugar level
      was evaluated 1/2 hour interval till 2 h after received respective juices. Data
      were collected for statistical analysis. RESULTS: The mean blood glucose
      concentration in bitter gourd group was not statistically significant between
      time points, (P = .176). However, 90 min after the intake of bitter gourd juice
      shows statistical significant reduction of blood glucose level when compare with
      fasting level, (p = .049). After Knol khol juice the mean blood glucose level
      differed statistically significant between time points, shown in (p = .029). But
      no statistical changes seen in ash gourd group. As a result bitter gourd juice is
      immediately reducing the blood glucose level, while Knol khol juice reduces the
      blood sugar level gradually for longer period of 120 min. CONCLUSION: This study
      shows the significance of hypoglycemic effects of bitter gourd and Knol khol
      juices among the type 2 Diabetic patients. Hence Bitter gourd juice, Knol khol
      juices may be beneficial in Diabetes patients to reduce the blood glucose level.

PMID- 29034202
TI  - Wound healing potentials of Thevetia peruviana: Antioxidants and inflammatory
      markers criteria.
AB  - Thevetia peruviana is a medicinal plant used in the treatment of external wounds,
      infected area, ring worms, tumours etc. in traditional system of medicine. The
      aim of the study was to evaluate the wound healing potentials of T. peruviana
      leaves hexane (LH) and fruit rind (FW) water extracts and to prove the folkloric
      claims. The antimicrobial, antioxidant and anti-inflammatory potentials could be
      important strategies in defining potent wound healing drug. Based on these
      approaches the current study was designed using incision, excision and dead space
      wound models with the biochemical, antioxidant enzymes and inflammatory marker
      analysis. The fruit rind water extract showed highest WBS of 1133 +/- 111.4 g.
      The extracts in excision model retrieved the excised wound i.e. complete healing
      of wound at day 14. The hydroxyproline content of FW and LH treated dry granuloma
      tissue was increased to 65.73 +/- 3.2 mg/g and 53.66 +/- 0.38 mg/g, accompanied
      by elevations of hexosamine and hexauronic acid with upregulation of GSH,
      catalase, SOD, peroxidase and the down regulation of the inflammatory marker (NO)
      and oxidative stress marker (LPO) in wet granulation tissue was documented.
      Conclusively, both the extracts showed enhanced WBS, rate of wound contraction,
      skin collagen tissue development, and early epithelisation. Therapeutic wound
      healing effect was further proven by reduced free radicals and inflammatory
      makers associated with enhanced antioxidants and connective tissue with
      histological evidence of more collagen formation. The present research could
      establish T. peruviana as potential source of effective wound healing drugs.

PMID- 29034204
TI  - Studies on analgesic, anti-inflammatory activities of stem and roots of Inula
      cuspidata C.B Clarke.
AB  - The present study was carried out to evaluate analgesic and anti-inflammatory
      activities in Inula cuspidata stem and root extracts along with heavy metals
      estimation in stem and root powder. Stem and roots were extracted with chloroform
      (ICSCE, ICRCE) and methanol (ICSME, ICRME). Acute oral toxicity of all extracts
      was determined by OECD guidelines 425. Analgesic activity was investigated by
      using hot plate and acetic acid induced writhing models. Anti-inflammatory
      activity (acute) of all extracts was evaluated by carrageenan induced paw edema
      model. In addition, root and stem powder was screened for heavy metals (As, Pb,
      Cd, Hg) estimation using atomic absorption spectroscopy. In acute toxicity study
      no mortality was observed when each extract was orally administered with 2.0
      g/kg. At the doses (100 and 200 mg/kg) ICRME followed by ICSME showed significant
      and dose dependent analgesic and anti-inflammatory effects compared with
      chloroform extracts. The heavy metals concentration in stem and root powders was
      found to be within the permissible limits as recommended by WHO for herbal raw
      materials. The findings of the present study validated the folkloric use of Inula
      cuspidata as analgesic and anti-inflammatory. In addition, the results intimate
      that heavy metals present in raw material were found to be within the defined
      limits, and it exhibits that the therapeutic efficacy of plant may not be
      effected, which can be otherwise possibly effected if the plant sequester high
      concentration of heavy metals from the polluted environment as well as from the
      soil rich in pesticides and sewage sludge etc.

PMID- 29034205
TI  - Kaempferia parviflora rhizome extract and Myristica fragrans volatile oil
      increase the levels of monoamine neurotransmitters and impact the proteomic
      profiles in the rat hippocampus: Mechanistic insights into their neuroprotective
      effects.
AB  - Potentially useful in the treatment of neurodegenerative disorders, Kaempferia
      parviflora and Myristica fragrans have been shown to possess a wide spectrum of
      neuropharmacological activities and neuroprotective effects in vivo and in vitro.
      In this study, we determined whether and how K. parviflora ethanolic extract and
      M. fragrans volatile oil could influence the levels of neurotransmitters and the
      whole proteomic profile in the hippocampus of Sprague Dawley (SD) rats. The
      effects of K. parviflora and M. fragrans on protein changes were analyzed by two
      dimensional gel electrophoresis (2D-gel), and proteins were identified by liquid
      chromatography tandem mass spectrometry (LC-MS/MS). The target proteins were then
      confirmed by Western blot. The levels of neurotransmitters were evaluated by
      reversed-phase high-performance liquid chromatography (RP-HPLC). The results
      showed that K. parviflora, M. fragrans and fluoxetine (the control drug for this
      study) increased serotonin, norepinephrine and dopamine in the rat hippocampus
      compared to that of the vehicle-treated group. Our proteomic data showed that 37
      proteins in the K. parviflora group were up-regulated, while 14 were down
      regulated, and 27 proteins in the M. fragrans group were up-regulated, while 16
      were down-regulated. In the fluoxetine treatment group, we found 29 proteins up
      regulated, whereas 14 proteins were down-regulated. In line with the proteomic
      data, the levels of GFAP, PDIA3, DPYSL2 and p-DPYSL2 were modified in the SD rat
      groups treated with K. parviflora, M. fragrans and fluoxetine as confirmed by
      Western blot. K. parviflora and M. fragrans mediated not only the levels of
      monoamine neurotransmitters but also the proteomic profiles in the rat
      hippocampus, thus shedding light on the mechanisms targeting neurodegenerative
      diseases.

PMID- 29034208
TI  - Prophylactic Cranial Irradiation Following Surgical Resection of Early-Stage
      Small-Cell Lung Cancer: A Review of the Literature.
AB  - With increasing use of low-dose screening CT scans, the diagnosis of early-stage
      small-cell lung cancer (SCLC) without evidence of mediastinal nodal or distant
      metastasis is likely to become more common, but the role of adjuvant therapies
      such as prophylactic cranial irradiation (PCI) are not well understood in this
      population. We performed a review of the literature pertaining to the impact of
      PCI in patients who underwent surgical resection of early-stage SCLC. Four
      studies were identified that were pertinent including three single-institution
      retrospective analyses and a National Cancer Database analysis. Based upon these
      studies, we estimate the rate of brain metastases to be 10-15% for Stage I and 15
      25% for Stage II disease without PCI. However, the impact of PCI on the
      development of brain metastases and its ultimate impact on overall survival were
      not consistent across these studies. In summary, there is sparse evidence to
      guide recommendations for PCI following resection of early-stage SCLC. While it
      may be reasonable to offer PCI to maximize likelihood of cure, alternative
      strategies such as observation with close imaging follow-up can also be
      considered for the appropriate patient given the known neurocognitive side
      effects of PCI.

PMID- 29034206
TI  - Leukemia-Initiating Cells in T-Cell Acute Lymphoblastic Leukemia.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy
      characterized by the clonal proliferation of immature T-cell precursors. T-ALL
      has many similar pathophysiological features to acute myeloid leukemia, which has
      been extensively studied in the establishment of the cancer stem cell (CSC)
      theory, but the CSC concept in T-ALL is still debatable. Although leukemia
      initiating cells (LICs), which can generate leukemia in a xenograft setting, have
      been found in both human T-ALL patients and animal models, the nature and origin
      of LICs are largely unknown. In this review, we discuss recent studies on LICs in
      T-ALL and the potential mechanisms of LIC emergence in this disease. We focus on
      the oncogenic transcription factors TAL1, LMO2, and NOTCH1 and highlight the
      significance of the transcriptional regulatory programs in normal hematopoietic
      stem cells and T-ALL.

PMID- 29034207
TI  - Targeting Novel but Less Common Driver Mutations and Chromosomal Translocations
      in Advanced Non-Small Cell Lung Cancer.
AB  - Discovery of the epidermal growth factor receptor gene mutation and the
      anaplastic lymphoma kinase chromosomal translocation in non-small cell lung
      cancer has prompted efforts around the world to identify many less common
      targetable oncogenic drivers. Such concerted efforts have been variably
      successful in both non-squamous and squamous cell carcinomas of the lung. Some of
      the targeted therapies for these oncogenic drivers have received regulatory
      approval for clinical use, while others have modest clinical benefit. In this
      mini-review, several of these targets will be reviewed.

PMID- 29034209
TI  - Bridge-Induced Translocation between NUP145 and TOP2 Yeast Genes Models the
      Genetic Fusion between the Human Orthologs Associated With Acute Myeloid
      Leukemia.
AB  - In mammalian organisms liquid tumors such as acute myeloid leukemia (AML) are
      related to spontaneous chromosomal translocations ensuing in gene fusions. We
      previously developed a system named bridge-induced translocation (BIT) that
      allows linking together two different chromosomes exploiting the strong
      endogenous homologous recombination system of the yeast Saccharomyces cerevisiae.
      The BIT system generates a heterogeneous population of cells with different
      aneuploidies and severe aberrant phenotypes reminiscent of a cancerogenic
      transformation. In this work, thanks to a complex pop-out methodology of the
      marker used for the selection of translocants, we succeeded by BIT technology to
      precisely reproduce in yeast the peculiar chromosome translocation that has been
      associated with AML, characterized by the fusion between the human genes NUP98
      and TOP2B. To shed light on the origin of the DNA fragility within NUP98, an
      extensive analysis of the curvature, bending, thermostability, and B-Z transition
      aptitude of the breakpoint region of NUP98 and of its yeast ortholog NUP145 has
      been performed. On this basis, a DNA cassette carrying homologous tails to the
      two genes was amplified by PCR and allowed the targeted fusion between NUP145 and
      TOP2, leading to reproduce the chimeric transcript in a diploid strain of S.
      cerevisiae. The resulting translocated yeast obtained through BIT appears
      characterized by abnormal spherical bodies of nearly 500 nm of diameter, absence
      of external membrane and defined cytoplasmic localization. Since Nup98 is a well
      known regulator of the post-transcriptional modification of P53 target genes, and
      P53 mutations are occasionally reported in AML, this translocant yeast strain can
      be used as a model to test the constitutive expression of human P53. Although the
      abnormal phenotype of the translocant yeast was never rescued by its expression,
      an exogenous P53 was recognized to confer increased vitality to the translocants,
      in spite of its usual and well-documented toxicity to wild-type yeast strains.
      These results obtained in yeast could provide new grounds for the interpretation
      of past observations made in leukemic patients indicating a possible involvement
      of P53 in cell transformation toward AML.

PMID- 29034211
TI  - The Role of ATRX in Glioma Biology.
AB  - The current World Health Organization classification of CNS tumors has made a
      tremendous leap from past editions by incorporating molecular criteria in
      addition to the pre-existing histological parameters. The revised version has had
      a particular impact on the classification of diffuse low-grade gliomas and their
      high-grade variants. The ATRX status is one of the critical markers that define
      the molecular classification of gliomas. In this review, we will first provide an
      overview of the role of ATRX in regular cell biology. Furthermore, the role of
      ATRX in tumorigenesis, specifically gliomas, is comprehensively elucidated. The
      possible correlation of ATRX status with other genetic/epigenetic modifications
      is also presented. We conclude by discussing some of the challenges associated
      with incorporating ATRX status assessment into routine clinical practice while
      also exploring opportunities for future diagnostics/therapeutics in gliomas based
      on ATRX status.

PMID- 29034212
TI  - Regulation of Proliferation by a Mitochondrial Potassium Channel in Pancreatic
      Ductal Adenocarcinoma Cells.
AB  - Previous results link the mitochondrial potassium channel Kv1.3 (mitoKv1.3) to
      the regulation of apoptosis. By synthesizing new, mitochondria-targeted
      derivatives (PAPTP and PCARBTP) of PAP-1, a specific membrane-permeant Kv1.3
      inhibitor, we have recently provided evidence that both drugs acting on mitoKv1.3
      are able to induce apoptosis and reduce tumor growth in vivo without affecting
      healthy tissues and cells. In the present article, by exploiting these new drugs,
      we addressed the question whether mitoKv1.3 contributes to the regulation of cell
      proliferation as well. When used at low concentrations, which do not compromise
      cell survival, both drugs slightly increased the percentage of cells in S phase
      while decreased the population at G0/G1 stage of cells from two different
      pancreatic ductal adenocarcinoma lines. Our data suggest that the observed
      modulation is related to ROS levels within the cells, opening the way to link
      mitochondrial ion channel function to downstream, ROS-related signaling events
      that might be important for cell cycle progression.

PMID- 29034210
TI  - Biomarkers for Response of Melanoma Patients to Immune Checkpoint Inhibitors: A
      Systematic Review.
AB  - BACKGROUND: Immune checkpoint inhibitors (ICIs), targeting CTLA-4 or PD-1
      molecules, have shown impressive therapeutic results. However, only 20-40% of
      advanced melanoma patients have durable responses to ICI, and these positive
      effects must be balanced against severe off-target immune toxicity and high
      costs. This urges the development of predictive biomarkers for ICI response to
      select patients with likely clinical benefit from treatment. Although many
      candidate biomarkers exist, a systematic overview of biomarkers and their
      usefulness is lacking. OBJECTIVES: Here, we systematically review the current
      literature of clinical data of ICI treatment to provide an overview of candidate
      predictive biomarkers for ICI in melanoma patients. METHODS: To identify studies
      on biomarkers for clinical response or survival to ICI therapy in melanoma
      patients, we performed a systematic search in OVID MEDLINE and retrieved 429
      publications, of which 67 met the eligibility criteria. RESULTS: Blood and
      genomic biomarkers were mainly studied for CTLA-4 ICI, while tumor tissue markers
      were analyzed for both CTLA-4 and PD-1 ICI. Blood cytology and soluble factors
      correlated more frequently to overall survival (OS) than to response, indicating
      their prognostic rather than predictive nature. Systemic T-cell response and
      regulation markers correlated to response, but progression-free survival or OS
      were not analyzed. Tumor tissue analyses revealed response correlations with
      mutational load, neoantigen load, immune-related gene expression, and CD8+ T-cell
      infiltration at the invasive margin. The predictive value of PD-L1 varied,
      possibly due to the influence of T-cell infiltration on tumor PD-L1 expression.
      Genomic biomarker studies addressed CTLA-4 and other immune-related genes.
      CONCLUSION: This review outlines all published biomarkers for ICI therapy and
      highlights potential candidate markers for future research. To date, PD-L1 is the
      best studied biomarker for PD-1 ICI response. The most promising candidate
      predictive biomarkers for ICI response have not yet been identified. Variations
      in outcome parameters, statistical power, and analyses hampered summary of the
      results. Further investigation of biomarkers in larger patient cohorts using
      standardized objectives and outcome measures is recommended.

PMID- 29034214
TI  - Pathogenic CD8+ T Cells Cause Increased Levels of VEGF-A in Experimental Malaria
      Associated Acute Respiratory Distress Syndrome, but Therapeutic VEGFR Inhibition
      Is Not Effective.
AB  - Malaria is a severe disease and kills over 400,000 people each year. Malarial
      complications are the main cause of death and include cerebral malaria and
      malaria-associated acute respiratory distress syndrome (MA-ARDS). Despite
      antimalarial treatment, lethality rates of MA-ARDS are still between 20 and 80%.
      Patients develop pulmonary edema with hemorrhages and leukocyte extravasation in
      the lungs. The vascular endothelial growth factor-A (VEGF-A) and the placental
      growth factor (PlGF) are vascular permeability factors and may be involved in the
      disruption of the alveolar-capillary membrane, leading to alveolar edema. We
      demonstrated increased pulmonary VEGF-A and PlGF levels in lungs of mice with
      experimental MA-ARDS. Depletion of pathogenic CD8+ T cells blocked pulmonary
      edema and abolished the increase of VEGF-A and PlGF. However, neutralization of
      VEGF receptor-2 (VEGFR-2) with the monoclonal antibody clone DC101 did not
      decrease pulmonary pathology. The broader spectrum receptor tyrosine kinase
      inhibitor sunitinib even increased lung pathology. These data suggest that the
      increase in alveolar VEGF-A and PlGF is not a cause but rather a consequence of
      the pulmonary pathology in experimental MA-ARDS and that therapeutic inhibition
      of VEGF receptors is not effective and even contra-indicated.

PMID- 29034213
TI  - A Promising Listeria-Vectored Vaccine Induces Th1-Type Immune Responses and
      Confers Protection Against Tuberculosis.
AB  - Deaths associated with tuberculosis (TB) is rising and accounted for 1.4 million
      deaths in 2015 many of which were due to drug-resistant bacteria. Vaccines
      represent an important medical intervention, but the current Bacilli Calmette
      Guerin (BCG) vaccine is not ideal for the protection of teenagers and adults.
      Therefore, a safe and effective vaccine is urgently needed. In this study, we
      designed a novel vaccine using an attenuated Listeria monocytogenes strain
      carrying fusion antigen FbpB-ESAT-6 (rLM) and characterized its safety and
      protective efficacy against Mycobacterium tuberculosis (M.tb) infection in mice.
      Compared to the wild type strain yzuLM4 and parental strain LMDeltaactA/plcB (LM1
      2), the virulence of rLM was significantly reduced as judged by its infectious
      kinetics and LD50 dose. Further characterization of intravenous immunization
      showed that prime-boost vaccination significantly increased the levels of Th1
      cytokines (IFN-gamma, IL-17, and IL-6), and enhanced cytotoxic T lymphocyte (CTL)
      CTLs activity, suggesting that rLM could elicit potent Th1/Th17 responses. More
      importantly, rLM significantly conferred the protection against M.tb H37Rv
      challenge. Collectively, our findings indicated that rLM is a novel and useful
      tool to prevent M.tb infection, and can be potentially be used to boost BCG
      primed immunity.

PMID- 29034216
TI  - A New Trick for a Conserved Enzyme: Mevalonate Kinase, a Glycosomal Enzyme, Can
      Be Secreted by Trypanosoma cruzi and Modulate Cell Invasion and Signaling. Is It
      Another Moonlighting Enzyme?

PMID- 29034215
TI  - The Proteome of Biologically Active Membrane Vesicles from Piscirickettsia
      salmonis LF-89 Type Strain Identifies Plasmid-Encoded Putative Toxins.
AB  - Piscirickettsia salmonis is the predominant bacterial pathogen affecting the
      Chilean salmonid industry. This bacterium is the etiological agent of
      piscirickettsiosis, a significant fish disease. Membrane vesicles (MVs) released
      by P. salmonis deliver several virulence factors to host cells. To improve on
      existing knowledge for the pathogenicity-associated functions of P. salmonis MVs,
      we studied the proteome of purified MVs from the P. salmonis LF-89 type strain
      using multidimensional protein identification technology. Initially, the
      cytotoxicity of different MV concentration purified from P. salmonis LF-89 was
      confirmed in an in vivo adult zebrafish infection model. The cumulative mortality
      of zebrafish injected with MVs showed a dose-dependent pattern. Analyses
      identified 452 proteins of different subcellular origins; most of them were
      associated with the cytoplasmic compartment and were mainly related to key
      functions for pathogen survival. Interestingly, previously unidentified putative
      virulence-related proteins were identified in P. salmonis MVs, such as outer
      membrane porin F and hemolysin. Additionally, five amino acid sequences
      corresponding to the Bordetella pertussis toxin subunit 1 and two amino acid
      sequences corresponding to the heat-labile enterotoxin alpha chain of Escherichia
      coli were located in the P. salmonis MV proteome. Curiously, these putative
      toxins were located in a plasmid region of P. salmonis LF-89. Based on the
      identified proteins, we propose that the protein composition of P. salmonis LF-89
      MVs could reflect total protein characteristics of this P. salmonis type strain.

PMID- 29034220
TI  - Head and Neck Lymphoma in an Iranian Population.
AB  - INTRODUCTION: This study is aimed to assess the prevalence and characteristics of
      head and neck lymphoma in a defined group of an Iranian population. MATERIALS AND
      METHODS: In this retrospective study, 126,450 biopsy reports from two referral
      Pathology Departments, (Tehran, the capital of Iran) were evaluated. In cases
      with head and neck lymphoma, other variables such as age, sex, specific location
      of lesions, and histopathological findings were recorded. Descriptive statistics
      were used to measure the prevalence and characteristics of head and neck lymphoma
      by means of SPSS soft ware, version 18. RESULTS: In total, 513 (0.4%) cases had
      head and neck lymphoma (46.9% male, 27.1% female) with a mean age of 46+/-6.2. Of
      the total lesions, 200 (0.15%) were Hodgkin lymphoma and 313 (0.25%) were non
      Hodgkin lymphoma. Nodular sclerosis was the most common (62.5%) histopathological
      subtype among Hodgkin lymphoma. In non-Hodgkin lymphoma, diffuse large B-cell
      lymphoma (62.3%) had the highest frequency. In Hodgkin disease, classic Hodgkin
      lymphocytic rich, mixed cellularity, and lymphocyte depletion were only seen in
      the neck compartment. Bone involvement was only found in Hodgkin nodular
      lymphocytic predominant variation. In non-Hodgkin lymphoma, the tongue, palate,
      and vestibular mucosa were affected only by diffuse large B-cell lymphoma. Jaw
      bones were only involved with diffuse large B-cell lymphoma compared to other
      bony structures. T-cell lymphoma and mucosal associated lymphoid tissue lymphoma
      were also found. CONCLUSION: Diffuse large B-cell lymphoma is the most common
      subtype of non-Hodgkin lymphoma especially in the tongue, palate, vestibular
      mucosa, and jaw bones.

PMID- 29034217
TI  - Evolution of Salmonella-Host Cell Interactions through a Dynamic Bacterial
      Genome.
AB  - Salmonella Typhimurium has a broad arsenal of genes that are tightly regulated
      and coordinated to facilitate adaptation to the various host environments it
      colonizes. The genome of Salmonella Typhimurium has undergone multiple gene
      acquisition events and has accrued changes in non-coding DNA that have undergone
      selection by regulatory evolution. Together, at least 17 horizontally acquired
      pathogenicity islands (SPIs), prophage-associated genes, and changes in core
      genome regulation contribute to the virulence program of Salmonella. Here, we
      review the latest understanding of these elements and their contributions to
      pathogenesis, emphasizing the regulatory circuitry that controls niche-specific
      gene expression. In addition to an overview of the importance of SPI-1 and SPI-2
      to host invasion and colonization, we describe the recently characterized
      contributions of other SPIs, including the antibacterial activity of SPI-6 and
      adhesion and invasion mediated by SPI-4. We further discuss how these fitness
      traits have been integrated into the regulatory circuitry of the bacterial cell
      through cis-regulatory evolution and by a careful balance of silencing and
      counter-silencing by regulatory proteins. Detailed understanding of regulatory
      evolution within Salmonella is uncovering novel aspects of infection biology that
      relate to host-pathogen interactions and evasion of host immunity.

PMID- 29034218
TI  - Deciphering Babesia-Vector Interactions.
AB  - Understanding host-pathogen-tick interactions remains a vitally important issue
      that might be better understood by basic research focused on each of the dyad
      interplays. Pathogens gain access to either the vector or host during tick
      feeding when ticks are confronted with strong hemostatic, inflammatory and immune
      responses. A prominent example of this is the Babesia spp.-tick-vertebrate host
      relationship. Babesia spp. are intraerythrocytic apicomplexan organisms spread
      worldwide, with a complex life cycle. The presence of transovarial transmission
      in almost all the Babesia species is the main difference between their life cycle
      and that of other piroplasmida. With more than 100 species described so far,
      Babesia are the second most commonly found blood parasite of mammals after
      trypanosomes. The prevalence of Babesia spp. infection is increasing worldwide
      and is currently classified as an emerging zoonosis. Babesia microti and Babesia
      divergens are the most frequent etiological agents associated with human
      babesiosis in North America and Europe, respectively. Although the Babesia-tick
      system has been extensively researched, the currently available prophylactic and
      control methods are not efficient, and chemotherapeutic treatment is limited.
      Studying the molecular changes induced by the presence of Babesia in the vector
      will not only elucidate the strategies used by the protozoa to overcome
      mechanical and immune barriers, but will also contribute toward the discovery of
      important tick molecules that have a role in vector capacity. This review
      provides an overview of the identified molecules involved in Babesia-tick
      interactions, with an emphasis on the fundamentally important ones for pathogen
      acquisition and transmission.

PMID- 29034222
TI  - Risk factor assessment in high-risk, bacillus Calmette-Guerin-treated, non-muscle
      invasive bladder cancer.
AB  - OBJECTIVE: To assess the risk factors associated with recurrence, progression and
      survival in high-risk non-muscle-invasive bladder cancer (NMIBC) patients treated
      with bacillus Calmette-Guerin (BCG) and validate the European Organization for
      Research and Treatment of Cancer (EORTC) and Spanish Urological Club for
      Oncological Treatment (CUETO) scores. PATIENTS AND METHODS: We retrospectively
      analyzed all BCG-treated NMIBC patients from 1998 to 2012. Multiple variables
      were tested as risk factors for recurrence-free survival and progression-free
      survival (PFS). Variables included age, sex, grade, stage, tumor size, number of
      tumors, carcinoma in situ (CIS), recurrence status, BCG strain used, smoking
      status, use of re-staging transurethral resection and use of single immediate
      postoperative instillation. We also tested the accuracy of EORTC and CUETO scores
      in predicting recurrence and progression. RESULTS: Overall, 123 patients were
      analyzed. Median (interquartile range) follow-up was 49 months. The 5-year
      overall survival, cancer-specific survival, recurrence-free survival and PFS were
      75.0%, 89.3%, 59.4% and 79.2%, respectively. On univariate analysis, multiple
      tumors (>=3), concomitant CIS and smoking influenced recurrence. Regarding
      progression, multiple tumors, concomitant CIS and Connaught strain (vs Tice)
      negatively influenced PFS on univariate and multivariate analyses were
      independent prognostic factors. CUETO scores were accurate, with a slight
      overestimation, while EORTC score was not predictive of recurrence or
      progression. CONCLUSION: In this study, CIS and tumor multiplicity were
      unfavorable predictors of recurrence and progression in patients with NMIBC
      receiving BCG. CUETO model was superior to EORTC risk tables in predicting
      recurrence and progression in our BCG-treated patient population. Nonetheless,
      both scores overestimated recurrence and progression rates. Prospective trials
      are needed to validate our findings.

PMID- 29034219
TI  - Rab GTPases in Immunity and Inflammation.
AB  - Strict spatiotemporal control of trafficking events between organelles is
      critical for maintaining homeostasis and directing cellular responses. This
      regulation is particularly important in immune cells for mounting specialized
      immune defenses. By controlling the formation, transport and fusion of
      intracellular organelles, Rab GTPases serve as master regulators of membrane
      trafficking. In this review, we discuss the cellular and molecular mechanisms by
      which Rab GTPases regulate immunity and inflammation.

PMID- 29034221
TI  - Atypical small acinar proliferation and two or more cores of high-grade
      intraepithelial neoplasia on a previous prostate biopsy are significant
      predictors of cancer during a transperineal template-guided saturation biopsy
      aimed at sampling one core for each 1 mL of prostate volume.
AB  - OBJECTIVE: The objective of this study was to evaluate whether high-grade
      prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar
      proliferation (ASAP) predict prostate cancer (PCa) during repeat transperineal
      template saturation biopsy with a high number of cores per prostate volume in
      patients with persistent clinical suspicion of PCa who underwent at least one
      previous negative transrectal ultrasound (TRUS)-guided biopsy. METHODS: We
      retrospectively evaluated 135 consecutive patients with persistent clinical
      suspicion of PCa, despite a set of negative TRUS-guided biopsies and increasing
      prostate-specific antigen levels; abnormal findings on digital rectal
      examination, TRUS, or magnetic resonance imaging; previous biopsy showing HGPIN;
      and previous biopsy showing atypical glands. Transperineal template saturation
      biopsy (TTSB) was performed at 5mm intervals to sample one core for each 1 mL of
      prostate volume. RESULTS: The median rate of biopsy cores per prostate volume was
      1.00 (range: 0.75-1.39). The PCa detection rates in patients who were diagnosed
      with HGPIN, or had two or more cores of HGPIN or ASAP, were 53% (9/17), 89%
      (8/9), and 83% (10/12), respectively. Two or more HGPIN cores and ASAP were
      positive predictors of PCa on TTSB. The high-grade cancer rates (Gleason score
      [GS] >=7) in patients with ASAP and two or more cores of HGPIN were 20% and 80%,
      respectively. The cancer detection rate represented by a GS score >=8 in patients
      with ASAP or two or more cores of HGPIN at a previous TRUS-guided biopsy was 5.5%
      (1/18). CONCLUSION: ASAP or two or more cores of HGPIN at a previous TRUS-guided
      biopsy strongly indicated the presence of PCa on TTSB.

PMID- 29034223
TI  - 'Alzheimer's Progression Score': Development of a Biomarker Summary Outcome for
      AD Prevention Trials.
AB  - BACKGROUND: Alzheimer's disease (AD) prevention research requires methods for
      measurement of disease progression not yet revealed by symptoms. Preferably, such
      measurement should encompass multiple disease markers. OBJECTIVES: Evaluate an
      item response theory (IRT) model-based latent variable Alzheimer Progression
      Score (APS) that uses multi-modal disease markers to estimate pre-clinical
      disease progression. DESIGN: Estimate APS scores in the BIOCARD observational
      study, and in the parallel PREVENT-AD Cohort and its sister INTREPAD placebo
      controlled prevention trial. Use BIOCARD data to evaluate whether baseline and
      early APS trajectory predict later progression to MCI/dementia. Similarly, use
      longitudinal PREVENT-AD data to assess test measurement invariance over time.
      Further, assess portability of the PREVENT-AD IRT model to baseline INTREPAD
      data, and explore model changes when CSF markers are added or withdrawn. SETTING:
      BIOCARD was established in 1995 and participants were followed up to 20 years in
      Baltimore, USA. The PREVENT-AD and INTREPAD trial cohorts were established
      between 2011-2015 in Montreal, Canada, using nearly identical entry criteria to
      enroll high-risk cognitively normal persons aged 60+ then followed for several
      years. PARTICIPANTS: 349 cognitively normal, primarily middle-aged participants
      in BIOCARD, 125 high-risk participants aged 60+ in PREVENT-AD, and 217 similar
      subjects in INTREPAD. 106 INTREPAD participants donated up to four serial CSF
      samples. MEASUREMENTS: Global cognitive assessment and multiple structural,
      functional, and diffusion MRI metrics, sensori-neural tests, and CSF
      concentrations of tau, Abeta42 and their ratio. RESULTS: Both baseline values and
      early slope of APS scores in BIOCARD predicted later progression to MCI or AD.
      Presence of CSF variables strongly improved such prediction. A similarly derived
      APS in PREVENT-AD showed measurement invariance over time and portability to the
      parallel INTREPAD sample. CONCLUSIONS: An IRT-based APS can summarize multimodal
      information to provide a longitudinal measure of pre-clinical AD progression, and
      holds promise as an outcome for AD prevention trials.

PMID- 29034224
TI  - Trends in Motor Performance of First Graders: A Comparison of Cohorts from 2006
      to 2015.
AB  - BACKGROUND: Motor performance is an important factor for health. Already in
      childhood, motor performance is associated with, e.g., obesity and risk factors
      for cardiovascular diseases. It is widely believed that the motor performance of
      children has declined over recent years. However, this belief is lacking clear
      evidence. The objective of this study was to examine trends in motor performance
      of first grade students during a period of 10 years (2006-2015). We examined
      trends in (a) aerobic fitness, (b) strength, (c) speed, and (d) balance for boys
      and girls separately and considered body mass index (BMI) as a potential
      confounder. METHODS: From 2006 to 2015, we tested 5,001 first graders [50.8%
      boys; mean age 6.76 (0.56) years] of 18 primary schools in Germany. Each year
      between 441 and 552 students of the same schools were surveyed. Performance tests
      were taken from the Motorik-Module Study and the "German Motor Ability Test": "6
      min run," "push-ups," "20-m sprint," and "static stand." Linear regression models
      were conducted for statistical analysis. RESULTS: A slightly negative trend in
      aerobic fitness performance was revealed in boys (beta = -0.050; p = 0.012) but
      not in girls. In the strength performance test no trend over time was detected.
      Performance in speed (boys: beta = -0.094; girls: beta = -0.143; p <= 0.001) and
      balance tests (boys: beta = -0.142; girls: beta = -0.232; p <= 0.001) increased
      over time for both boys and girls. These findings held true when BMI was
      considered. CONCLUSION: This study only partly supported the assumption that
      motor performance of children has declined: in our study, aerobic fitness
      declined (only in boys), while strength remained stable and speed and balance
      even increased in both sexes. Moreover, it seems as if BMI can explain changes in
      performance only to a small extent. Changed lifestyles might be a substantial
      cause. Further research on recent trends of motor performance and interacting
      variables is needed to support the results of our study and to provide more
      knowledge on causes of these trends.

PMID- 29034225
TI  - The Perception of a Three-Dimensional-Printed Heart Model from the Perspective of
      Different Stakeholders: A Complex Case of Truncus Arteriosus.
AB  - The case of an 11-year-old male patient with truncus arteriosus is presented. The
      patient has a right aortic arch, a repaired truncus arteriosus, pulmonary artery
      stenosis, as well as conduit stenosis, with a complex surgical plan being
      discussed. In order to gather additional insight into the patient's anatomy prior
      to the surgery and to facilitate communication with the patient's parents, a
      three-dimensional (3D) model of his heart and main vessels was created from
      computed tomography data. Feedback was collected from different stakeholders. The
      patient and his parents were both struck by the size of the heart, with the
      parents further elaborating on how the 3D model was more intuitive a tool than
      medical images as well as "an helpful talking point to the other members of the
      family" and potentially also at school. The surgeon and cardiologist commented on
      gaining better understanding of the 3D relationship between a markedly narrowed
      right pulmonary artery and the aorta, with the surgeon ultimately coming to a
      decision of dividing the ascending aorta quite high to access the right pulmonary
      artery for patch reconstruction and thus planning to arrest the circulation
      beforehand. The imaging expert remarked on the potential to "improve
      communication in multidisciplinary meetings," while a medical trainee, who also
      had a chance to evaluate the model, remarked that "having the model in front of
      me and being able to see the exact abnormality makes this particular case much
      more memorable. [...] 3D printed models could have immense potential in pathology
      and anatomy teaching for the training of healthcare professionals."

PMID- 29034228
TI  - Commentary: Outbreak of Chikungunya in Pakistan.

PMID- 29034227
TI  - Psychostimulants As Cognitive Enhancers in Adolescents: More Risk than Reward?
AB  - Methylphenidate and other psychostimulants, originally developed to treat
      attention deficit-hyperactivity disorder, are increasingly abused by healthy
      adolescents and adults seeking an advantage in scholastic performance and work
      productivity. However, how these drugs may affect cognitive performance,
      especially in the young brain, remains unclear. Here, we review recent literature
      and emphasize the risks of abuse of psychostimulants in healthy adolescents and
      young adults. We conclude that while the desire for cognitive enhancement,
      particularly with rising costs of education and increasingly competitive nature
      of scholarship programs, is unlikely to diminish in the near future, it is
      crucial for the scientific community to thoroughly examine the efficacy and
      safety of these stimulants in healthy populations across development. The current
      dearth of knowledge on the dose-response curve, metabolism, and cognitive
      outcomes in adolescents following methylphenidate or other psychostimulant
      exposure may be perpetuating a perception of these drugs as "safe" when that
      might not be true for developing brains.

PMID- 29034229
TI  - Spatiotemporal Modeling for Fine-Scale Maps of Regional Malaria Endemicity and
      Its Implications for Transitional Complexities in a Routine Surveillance Network
      in Western Cambodia.
AB  - Due to the associated and substantial efforts of many stakeholders involved in
      malaria containment, the disease burden of malaria has dramatically decreased in
      many malaria-endemic countries in recent years. Some decades after the past
      efforts of the global malaria eradication program, malaria elimination has again
      featured on the global health agenda. While risk distribution modeling and a
      mapping approach are effective tools to assist with the efficient allocation of
      limited health-care resources, these methods need some adjustment and
      reexamination in accordance with changes occurring in relation to malaria
      elimination. Limited available data, fine-scale data inaccessibility (for
      example, household or individual case data), and the lack of reliable data due to
      inefficiencies within the routine surveillance system, make it difficult to
      create reliable risk maps for decision-makers or health-care practitioners in the
      field. Furthermore, the risk of malaria may dynamically change due to various
      factors such as the progress of containment interventions and environmental
      changes. To address the complex and dynamic nature of situations in low-to
      moderate malaria transmission settings, we built a spatiotemporal model of a
      standardized morbidity ratio (SMR) of malaria incidence, calculated through
      annual parasite incidence, using routinely reported surveillance data in
      combination with environmental indices such as remote sensing data, and the non
      environmental regional containment status, to create fine-scale risk maps. A
      hierarchical Bayesian frame was employed to fit the transitioning malaria risk
      data onto the map. The model was set to estimate the SMRs of every study location
      at specific time intervals within its uncertainty range. Using the spatial
      interpolation of estimated SMRs at village level, we created fine-scale maps of
      two provinces in western Cambodia at specific time intervals. The maps presented
      different patterns of malaria risk distribution at specific time intervals.
      Moreover, the visualized weights estimated using the risk model, and the
      structure of the routine surveillance network, represent the transitional
      complexities emerging from ever-changing regional endemic situations.

PMID- 29034230
TI  - Resilient Health System As Conceptual Framework for Strengthening Public Health
      Disaster Risk Management: An African Viewpoint.

PMID- 29034231
TI  - Editorial: The Vascular Niche in Tissue Repair: A Therapeutic Target for
      Regeneration.

PMID- 29034226
TI  - An Overview of Heart Rate Variability Metrics and Norms.
AB  - Healthy biological systems exhibit complex patterns of variability that can be
      described by mathematical chaos. Heart rate variability (HRV) consists of changes
      in the time intervals between consecutive heartbeats called interbeat intervals
      (IBIs). A healthy heart is not a metronome. The oscillations of a healthy heart
      are complex and constantly changing, which allow the cardiovascular system to
      rapidly adjust to sudden physical and psychological challenges to homeostasis.
      This article briefly reviews current perspectives on the mechanisms that generate
      24 h, short-term (~5 min), and ultra-short-term (<5 min) HRV, the importance of
      HRV, and its implications for health and performance. The authors provide an
      overview of widely-used HRV time-domain, frequency-domain, and non-linear
      metrics. Time-domain indices quantify the amount of HRV observed during
      monitoring periods that may range from ~2 min to 24 h. Frequency-domain values
      calculate the absolute or relative amount of signal energy within component
      bands. Non-linear measurements quantify the unpredictability and complexity of a
      series of IBIs. The authors survey published normative values for clinical,
      healthy, and optimal performance populations. They stress the importance of
      measurement context, including recording period length, subject age, and sex, on
      baseline HRV values. They caution that 24 h, short-term, and ultra-short-term
      normative values are not interchangeable. They encourage professionals to
      supplement published norms with findings from their own specialized populations.
      Finally, the authors provide an overview of HRV assessment strategies for
      clinical and optimal performance interventions.

PMID- 29034232
TI  - Maternally Contributed Folate Receptor 1 Is Expressed in Ovarian Follicles and
      Contributes to Preimplantation Development.
AB  - Folates have been shown to play a crucial role for proper development of the
      embryo as folate deficiency has been associated with reduced developmental
      capacity such as increased risk of fetal neural tube defects and spontanous
      abortion. Transcripts encoding the reduced folate carrier RFC1 (SLC19A1 protein)
      and the high-affinity folate receptor FOLR1 are expressed in oocytes and
      preimplantation embryos, respectively. In this study, we observed maternally
      contributed FOLR1 protein during mouse and human ovarian follicle development,
      and 2-cell mouse embryos. In mice, FOLR1 was highly enriched in oocytes from
      primary, secondary and tertiary follicles, and in the surrounding granulosa
      cells. Interestingly, during human follicle development, we noted a high and
      specific presence of FOLR1 in oocytes from primary and intermediate follicles,
      but not in the granulosa cells. The distribution of FOLR1 in follicles was noted
      as membrane-enriched but also seen in the cytoplasm in oocytes and granulosa
      cells. In 2-cell embryos, FOLR1-eGFP fusion protein was detected as cytoplasmic
      and membrane-associated dense structures, resembling the distribution pattern
      observed in ovarian follicle development. Knock-down of Folr1 mRNA function was
      accomplished by microinjection of short interference (si)RNA targeting Folr1,
      into mouse pronuclear zygotes. This revealed a reduced capacity of Folr1 siRNA
      treated embryos to develop to blastocyst compared to the siRNA-scrambled control
      group, indicating that maternally contributed protein and zygotic transcripts
      sustain embryonic development combined. In summary, maternally contributed FOLR1
      protein appears to maintain ovarian functions, and contribute to preimplantation
      development combined with embryonically synthesized FOLR1.

PMID- 29034236
TI  - Prognostic Value of the New Prostate Cancer International Society of Urological
      Pathology Grade Groups.
AB  - Gleason grading is the best independent predictor for prostate cancer (PCa)
      progression. Recently, a new PCa grading system has been introduced by the
      International Society of Urological Pathology (ISUP) and is recommended by the
      World Health Organization (WHO). Following studies observed more accurate and
      simplified grade stratification of the new system. Aim of this study was to
      compare the prognostic value of the new grade groups compared to the former
      Gleason Grading and to determine whether re-definition of Gleason Pattern 4 might
      reduce upgrading from prostate biopsy to radical prostatectomy (RP) specimen. A
      cohort of men undergoing RP from 2002 to 2015 at the Hospital of Goeppingen
      (Goeppingen, Germany) was used for this study. In total, 339 pre-operative
      prostatic biopsies and corresponding RP specimens, as well as additional 203 RP
      specimens were re-reviewed for Grade Groups according to the ISUP. Biochemical
      recurrence-free survival (BFS) after surgery was used as endpoint to analyze
      prognostic significance. Other clinicopathological data included TNM-stage and
      pre-operative PSA level. Kaplan-Meier analysis revealed risk stratification of
      patients based on both former Gleason Grading and ISUP Grade Groups, and was
      statistically significant using the log-rank test (p < 0.001). Both grading
      systems significantly correlated with TNM-stage and pre-operative PSA level (p <
      0.001). Higher tumor grade in RP specimen compared to corresponding pre-operative
      biopsy was observed in 44 and 34.5% of cases considering former Gleason Grading
      and ISUP Grade Groups, respectively. Both, former Gleason Grading and ISUP Grade
      Groups predict survival when applied on tumors in prostatic biopsies as well as
      RP specimens. This is the first validation study on a large representative German
      community-based cohort to compare the former Gleason Grading with the recently
      introduced ISUP Grade Groups. Our data indicate that the ISUP Grade Groups do not
      improve predictive value of PCa grading and might be less sensitive in
      deciphering tumors with 3 + 4 and 4 + 3 pattern on RP specimen. However, the
      Grade Group system results less frequently in an upgrading from biopsy to the
      corresponding RP specimens, indicating a lower risk to miss potentially
      aggressive tumors not represented on biopsies.

PMID- 29034234
TI  - Interleukin-13 in Asthma and Other Eosinophilic Disorders.
AB  - Asthma is characterized by episodic, reversible airflow obstruction associated
      with variable levels of inflammation. Over the past several decades, there has
      been an increasing appreciation that the clinical presentation of asthma
      comprises a diverse set of underlying pathologies. Rather than being viewed as a
      single disease entity, asthma is now thought of as a clinical syndrome with the
      involvement of multiple pathological mechanisms. While it is appreciated that
      eosinophilia is present in only a subset of patients, it remains a key feature of
      asthma and other eosinophilic disorders such as atopic dermatitis, eosinophilic
      esophagitis, and chronic rhinosinusitis with nasal polyps. Eosinophils are bone
      marrow-derived leukocytes present in low numbers in health; however, during
      disease the type 2 cytokines [interleukins (IL)-4, -5, and -13] can induce rapid
      eosinophilopoiesis, prolonged eosinophil survival, and trafficking to the site of
      injury. In diseases such as allergic asthma there is an aberrant inflammatory
      response leading to eosinophilia, tissue damage, and airway pathology. IL-13 is a
      pleiotropic type 2 cytokine that has been shown to be integral in the
      pathogenesis of asthma and other eosinophilic disorders. IL-13 levels are
      elevated in animal models of eosinophilic inflammation and in the blood and
      tissue of patients diagnosed with eosinophilic disorders. IL-13 signaling elicits
      many pathogenic mechanisms including the promotion of eosinophil survival,
      activation, and trafficking. Data from preclinical models and clinical trials of
      IL-13 inhibitors in patients have revealed mechanistic insights into the role of
      this cytokine in driving eosinophilia. Promising results from clinical trials
      further support a key mechanistic role of IL-13 in asthma and other eosinophilic
      disorders. Here, we provide a perspective on the role of IL-13 in asthma and
      other eosinophilic disorders and describe ongoing clinical trials targeting this
      pathway in patients with significant unmet medical needs.

PMID- 29034235
TI  - Coagulofibrinolytic Changes in Patients with Post-cardiac Arrest Syndrome.
AB  - Whole-body ischemia and reperfusion due to cardiac arrest and subsequent return
      of spontaneous circulation constitute post-cardiac arrest syndrome (PCAS), which
      consists of four syndromes including systemic ischemia/reperfusion responses and
      post-cardiac arrest brain injury. The major pathophysiologies underlying systemic
      ischemia/reperfusion responses are systemic inflammatory response syndrome and
      increased coagulation, leading to disseminated intravascular coagulation (DIC),
      which clinically manifests as obstruction of microcirculation and multiple organ
      dysfunction. In particular, thrombotic occlusion in the brain due to DIC,
      referred to as the "no-reflow phenomenon," may be deeply involved in post-cardiac
      arrest brain injury, which is the leading cause of mortality in patients with
      PCAS. Coagulofibrinolytic changes in patients with PCAS are characterized by
      tissue factor-dependent coagulation, which is accelerated by impaired
      anticoagulant mechanisms, including antithrombin, protein C, thrombomodulin, and
      tissue factor pathway inhibitor. Damage-associated molecular patterns (DAMPs)
      accelerate not only tissue factor-dependent coagulation but also the factor XII-
      and factor XI-dependent activation of coagulation. Inflammatory cytokines are
      also involved in these changes via the expression of tissue factor on endothelial
      cells and monocytes, the inhibition of anticoagulant systems, and the release of
      neutrophil elastase from neutrophils activated by inflammatory cytokines.
      Hyperfibrinolysis in the early phase of PCAS is followed by inadequate endogenous
      fibrinolysis and fibrinolytic shutdown by plasminogen activator inhibitor-1.
      Moreover, cell-free DNA, which is also a DAMP, plays a pivotal role in the
      inhibition of fibrinolysis. DIC diagnosis criteria or fibrinolysis markers,
      including d-dimer and fibrin/fibrinogen degradation products, which are commonly
      tested in patients and easily accessible, can be used to predict the mortality or
      neurological outcome of PCAS patients with high accuracy. A number of studies
      have explored therapy for this unique pathophysiology since the first report on
      "no-reflow phenomenon" was published roughly 50 years ago. However, the optimum
      therapeutic strategy focusing on the coagulofibrinolytic changes in cardiac
      arrest or PCAS patients has not yet been established. The elucidation of more
      precise pathomechanisms of coagulofibrinolytic changes in PCAS may aid in the
      development of novel therapeutic targets, leading to an improvement in the
      outcomes of PCAS patients.

PMID- 29034233
TI  - Role of Cardiolipin in Mitochondrial Signaling Pathways.
AB  - The phospholipid cardiolipin (CL) is an essential constituent of mitochondrial
      membranes and plays a role in many mitochondrial processes, including respiration
      and energy conversion. Pathological changes in CL amount or species composition
      can have deleterious consequences for mitochondrial function and trigger the
      production of reactive oxygen species. Signaling networks monitor mitochondrial
      function and trigger an adequate cellular response. Here, we summarize the role
      of CL in cellular signaling pathways and focus on tissues with high-energy
      demand, like the heart. CL itself was recently identified as a precursor for the
      formation of lipid mediators. We highlight the concept of CL as a signaling
      platform. CL is exposed to the outer mitochondrial membrane upon mitochondrial
      stress and CL domains serve as a binding site in many cellular signaling events.
      During mitophagy, CL interacts with essential players of mitophagy like Beclin 1
      and recruits the autophagic machinery by its interaction with LC3. Apoptotic
      signaling pathways require CL as a binding platform to recruit apoptotic factors
      such as tBid, Bax, caspase-8. CL required for the activation of the inflammasome
      and plays a role in inflammatory signaling. As changes in CL species composition
      has been observed in many diseases, the signaling pathways described here may
      play a general role in pathology.

PMID- 29034238
TI  - Exploring the Abnormal Modulation of the Autonomic Systems during Nasal Flow
      Limitation in Upper Airway Resistance Syndrome by Hilbert-Huang Transform.
AB  - : Patients with nasal flow limitation and upper airway resistance syndrome (UARS)
      during sleep can present with low blood pressure and disturbing symptoms
      associated with hypervagotony. We hypothesized that the dynamic changes of the
      autonomic system related to inspiratory flow limitation can be quantified by the
      developed analytic technique applied on beat-to-beat heart rate (RR intervals)
      and finger photoplethysmography (PPG). METHOD: A breath-by-breath investigation
      based on the Hilbert-Huang transform was performed to explore autonomic nervous
      system changes observed during inspiratory flow limitation. Autonomic status was
      quantified from beat-to-beat heart rate analysis by high frequency (RRHF; 0.15
      0.4 Hz), low frequency (RRLF; 0.04-0.15 Hz), and LF/HF ratio of each respiratory
      cycle. Based on respiratory-related mechanisms contained in the PPG signal, we
      further quantified the respiratory-related oscillations (PPGres). Based on
      esophageal pressure and nasal flow measurements, each respiratory cycle was
      identified and breathing patterns were classified into one of four groups:
      normal, inspiratory flow limitation cycles without increased effort [FL(-)],
      minimal inspiratory flow limitation with effort, and inspiratory flow limitation
      cycles with increased effort [FL(+)]. The resulting quantitative parameters of
      the identified cycles were calculated. RESULTS: 49 UARS patients (12 males; aged
      26.8 +/- 5.8 years) with apnea-hypopnea index (AHI) 3.1 +/- 1.5 per hour and nine
      aged matched control subjects (3 males; aged 27.8 +/- 4.0 years) with AHI 0.8 +/-
      1.1 per hour were retrospectively identified. Compared to the control group,
      hyperactivation of the parasympathetic system was noted during stage 2 NREM sleep
      by RRHF (27.8 +/- 18.2 vs 22.5 +/- 11.12, p < 0.05) in 49 UARS patients. Analysis
      of the different classifications of respiratory cycles indicated that during
      "high" (increased) respiratory efforts, the RRHF and PPGres were significantly
      higher compared to "normal cycle" and "FL(-)" groups. The RRLF/RRHF (an index of
      sympathetic activity) was significantly lower in the "FL(+)" group (1.66 +/-
      0.80) than in the "normal cycle" (1.93 +/- 0.97, p < 0.05) and "FL(-)" groups
      (2.01 +/- 1.01, p < 0.05). CONCLUSION: The proposed algorithm allows quantifying
      the temporal changes of specific mechanisms of the autonomic system on breath-by
      breath basis. With no or very limited impact on oxygen saturation, the
      hyperactivation of parasympathetic system in associated with inspiratory flow
      limitation or increased respiratory efforts during stage 2 NREM sleep has been
      presented in this study.

PMID- 29034237
TI  - Proteomics of Eosinophil Activation.
AB  - We recently identified and quantified >7,000 proteins in non-activated human
      peripheral blood eosinophils using liquid chromatography coupled to tandem mass
      spectrometry (LC-MS/MS) and described phosphoproteomic changes that accompany
      acute activation of eosinophils by interleukin-5 (IL5) (1). These data comprise a
      treasure trove of information about eosinophils. We illustrate the power of label
      free LC-MS/MS quantification by considering four examples: complexity of
      eosinophil STATs, contribution of immunoproteasome subunits to eosinophil
      proteasomes, complement of integrin subunits, and contribution of platelet
      proteins originating from platelet-eosinophil complexes to the overall proteome.
      We describe how isobaric labeling enables robust sample-to-sample comparisons and
      relate the 220 phosphosites that changed significantly upon treatment with IL5 to
      previous studies of eosinophil activation. Finally, we review previous attempts
      to leverage the power of mass spectrometry to discern differences between
      eosinophils of healthy subjects and those with eosinophil-associated conditions
      and point out features of label-free quantification and isobaric labeling that
      are important in planning future mass spectrometric studies.

PMID- 29034239
TI  - Hepatoid Adenocarcinoma of the Stomach: A Challenging Diagnostic and Therapeutic
      Disease through a Case Report and Review of the Literature.
AB  - Hepatoid adenocarcinoma of the stomach (HAS) is a rare aggressive tumor with
      hepatocellular differentiation. HAS often produces alpha fetoprotein (AFP) and
      metastasizes to the lymph nodes and the liver. Molecular studies revealed Her2
      amplification and overexpression, association with p53 mutations, but no
      association with KRAS mutations. EGFR and BRAF mutations have not yet been
      evaluated in hepatoid carcinoma of the stomach so far. Hereby, we present a case
      of a 41-year-old female patient with HAS with high AFP level and liver
      metastases. Molecular analysis revealed Her2 overexpression by
      immunohistochemistry (IHC), but no EGFR, KRAS, or BRAF mutations were detected.
      The patient underwent chemotherapy type DCX (docetaxel, cisplatinum, and
      capecitabine) every 3 weeks with partial response after two cycles, maintained
      for eight cycles, and then was on maintenance therapy with trastuzumab for 7
      months before relapsing and dying 18 months from the day of diagnosis.
      Conclusively, HAS may be misdiagnosed as hepatocellular carcinoma; therefore, it
      should be considered in the differential diagnosis of multiple hepatic nodules
      with high AFP and no history of hepatitis, liver fibrosis or cirrhosis.

PMID- 29034240
TI  - Dark Chocolate: Opportunity for an Alliance between Medical Science and the Food
      Industry?
AB  - Dark chocolate (DC) was originally introduced in human nutrition as a medicinal
      product consumable in a liquid form. Century-long efforts of food industry
      transformed this hardly appealing product into a valuable modern culinary delight
      with clear predominance of confectionery brands of DC on the market. However,
      current epidemiological data as well as multiple experimental and clinical
      observations reveal that DC consumption may have a profound effect on
      cardiovascular, central nervous systems, hemostasis, and lipid metabolism.
      However, despite of growing body of modern scientific evidence revealing
      medicinal properties of cocoa-based products, DC remains more gourmet culinary
      item than medicinal food product. Even today there are no clear dietary
      recommendations on consumption of cocoa flavonoids (flavanols) for health
      purpose. Clinical trials with DC rarely include monitoring of plasma flavanol
      concentration in volunteers. Moreover, there is no standardized assay or any
      quantitative requirements for flavanol content in the commercial brands of DC.
      High flavanol content is often sacrificed during manufacturing for a better taste
      of DC due to bitterness of cocoa flavonoids. All these problems including
      subsequently arising ethical issues need to be addressed by joint efforts of food
      industry and medical science. Moreover, application of microencapsulation
      technology in DC manufacturing, as well as molecular selection of best flavanol
      producers may drastically change bioavailability of DC bioactive ingredients and
      DC production technology. Nevertheless, only strict causative approach, linking
      possible health effect of DC to its bioactive ingredients considered as
      nutraceuticals, may change the current landscape in nutritional research related
      to cocoa-based products and create a trustworthy path for their medicinal use.

PMID- 29034242
TI  - Commentary: Snap-N-Send: A Valid and Reliable Method for Assessing the Energy
      Intake of Elite Adolescent Athletes.

PMID- 29034241
TI  - Bone Mineral Density after Weight Gain in 160 Patients with Anorexia Nervosa.
AB  - Low bone mineral density (BMD) is a frequent complication in anorexia nervosa
      (AN). There are controversial points of views regarding the restoration of bone
      mineralization after recovery in AN. We aimed to assess changes of BMD at 3 years
      in patients with AN and to explore the relationships between body composition,
      physical activity, and BMD. Patients with AN were included from 2009 to 2011 in a
      first visit (T0) with evaluation of weight, height, body mass index (BMI), body
      composition [fat mass (FM) and fat-free mass], and BMD. Those who had low BMD,
      either osteoporosis or osteopenia, were admitted in a second visit (T1) to carry
      out a new bone densitometry examination and body composition; they were also
      asked for their physical activity. At T0, our study involved 160 patients. Low
      BMD was observed in 53.6% of them and significant factors associated with
      demineralization were lower BMIs (16.5 +/- 2.1 vs 17.3 +/- 2.3 kg/m2, p = 0.01)
      and higher duration of AN (11.4 +/- 10.5 vs 6.4 +/- 6.5 years, p = 0.001). At 3
      years follow-up (T1), 42 patients were involved and no significant changes in BMD
      were observed despite body weight increase (3.8 +/- 6.1 kg). Interestingly, FM
      gain was a significant factor associated with BMD improvement at follow-up (8.0
      +/- 9.1 vs 3.0 +/- 3.5 kg, p = 0.02). Our findings suggest that the restoration
      of normal bone values is not related to the increase of body weight, at least
      after 3 years. FM seems to play an important role in the pathophysiological
      mechanism of osteoporosis and osteopenia in AN.

PMID- 29034243
TI  - Improving Surgical Outcome Using Diffusion Tensor Imaging Techniques in Deep
      Brain Stimulation.
AB  - INTRODUCTION: Recent advances in surgical imaging include the use of diffusion
      tensor imaging (DTI) in deep brain stimulation (DBS) and provide a detailed view
      of the white matter tracts and their connections which are not seen with
      conventional magnetic resonance imaging. Given that the efficacy of DBS depends
      on the precise and accurate targeting of these circuits, better surgical planning
      using information obtained from DTI may lead to improved surgical outcome. We aim
      to review the available literature to evaluate the efficacy of such a strategy.
      METHODS: A search of PubMed was performed to identify all articles using the
      search terms "(diffusion tractography OR diffusion tensor imaging OR DTI) AND
      (deep brain stimulation OR DBS)." Studies were included if DTI was used and
      clinical outcomes were reported. RESULTS: We identified 35 studies where the use
      of DTI in DBS was evaluated. The most studied pathology was movement disorders
      (17 studies), psychiatric disorders (11 studies), and pain (7 studies). The
      overall responder rates for tremor reduction was 70.0% (SD = 26.1%) in 69
      patients, 36.5% (SD = 19.1%) for obsessive-compulsive disorder in 9 patients,
      48.3% (SD = 40.0%) for depression in 40 patients, and 49.7% (SD = 35.1%) for
      chronic pain in 23 patients. DISCUSSION: The studies reviewed show that the use
      of DTI for surgical planning is feasible, provide additional information over
      conventional targeting methods, and can improve surgical outcome. Patients in
      whom the DBS electrodes were within the DTI targets experienced better outcomes
      than those in whom the electrodes were not. Many current studies are limited by
      their small sample size or retrospective nature. The use of DTI in DBS planning
      appears underutilized and further studies are warranted given that surgical
      outcome can be optimized using this non-invasive technique.

PMID- 29034245
TI  - Handshakes and Fights: The Regulatory Interplay of RNA-Binding Proteins.
AB  - What drives the flow of signals controlling the outcome of post-transcriptional
      regulation of gene expression? This regulatory layer, presiding to processes
      ranging from splicing to mRNA stability and localization, is a key determinant of
      protein levels and thus cell phenotypes. RNA-binding proteins (RBPs) form a
      remarkable army of post-transcriptional regulators, strong of more than 1,500
      genes implementing this expression fine-tuning plan and implicated in both cell
      physiology and pathology. RBPs can bind and control a wide array of RNA targets.
      This sheer amount of interactions form complex regulatory networks (PTRNs) where
      the action of individual RBPs cannot be easily untangled from each other. While
      past studies have mostly focused on the action of individual RBPs on their
      targets, we are now observing an increasing amount of evidence describing the
      occurrence of interactions between RBPs, defining how common target RNAs are
      regulated. This suggests that the flow of signals in PTRNs is driven by the
      intertwined contribution of multiple RBPs, concurrently acting on each of their
      targets. Understanding how RBPs cooperate and compete is thus of paramount
      importance to chart the wiring of PTRNs and their impact on cell phenotypes. Here
      we review the current knowledge about patterns of RBP interaction and attempt at
      describing their general principles. We also discuss future directions which
      should be taken to reach a comprehensive understanding of this fundamental aspect
      of gene expression regulation.

PMID- 29034244
TI  - Contemporary Strategies in the Management of Civilian Neck Zone II Vascular
      Trauma.
AB  - Neck trauma is the leading cause of death mainly in younger persons posing to
      surgeons the dilemma whether to proceed with reconstruction of vascular injuries
      either in the presence of coma or in severe neurological deficit. Vascular
      injuries in zone II predominate over the other injuries located in zones I/III of
      the neck. Conventional open repair of carotid injuries with primary closure or
      interposition grafting is always recommended due to the effective long-term
      results for penetrating injuries or for patients unfit for endovascular
      intervention. In cases of blunt trauma, anticoagulation or antiplatelet therapy
      should be administered first in neurologically stable patients. In case of
      worsening of the neurological status of the patient despite adequate
      anticoagulation endovascular means should be considered in cases of appropriate
      anatomy of the arterial trauma. We provide an update on penetrating/blunt trauma
      in zone II of the neck, giving emphasis on the anticoagulant and endovascular
      treatment.

PMID- 29034246
TI  - Tolvaptan for the Treatment of Enlarged Polycystic Liver Disease.
AB  - A 44-year-old Japanese woman with autosomal dominant polycystic kidney disease
      was admitted to our hospital for evaluation of abdominal distension. Her eGFR was
      53.7 mL/min/1.73 m2. Total kidney volume was 2,614 mL. Tolvaptan (60 mg/day) was
      started to treat renal involvement. The patient's abdominal fullness began to
      improve and liver volume, indicating advanced polycystic liver disease (PLD),
      decreased from 9,750 mL to 8,345 mL after 17 months of tolvaptan treatment,
      though there was no significant change in kidney volume. This case indicates that
      tolvaptan may be a therapeutic option for hepatomegaly in patients with
      symptomatic PLD.

PMID- 29034247
TI  - Regular Exposure to Cowbells Affects the Behavioral Reactivity to a Noise
      Stimulus in Dairy Cows.
AB  - In alpine regions, cows are often equipped with bells during pasture season to
      ensure that farmers can locate them. Constant exposure to the chime of a bell may
      affect cows' acoustic perception in general. The aim of this study is to test
      whether routine bell exposure affects the reactivity to a noise stimulus and
      might be associated with hearing impairment in cows. For the assessment,
      behavioral and cardiac indicators were used as indirect measures of hearing
      capacity. Cows that were either used to wearing a bell or not were exposed to a
      playback of low and high amplitude (=varying loudness). In addition, we tested
      whether wearing earplugs, mimicking hearing impairment, reduced the cows'
      reactivity toward the playback. On 24 farms, half of them routinely using
      cowbells, 96 Brown Swiss cows were tested in a 2 * 2 factorial cross-over design
      (65 or 85 dB, without or with earplugs) in a balanced order. The effects of bell
      experience, amplitude, and earplugs on the latency to the first behavioral and
      cardiac response to a 5-s playback were analyzed using linear mixed-effects
      models, considering dependencies within the data set. Cows reacted faster without
      earplugs and when they were exposed to 85 dB compared with 65 dB. The proportion
      of cows leaving the feeding rack after onset of the playback was reduced by bell
      experience and earplugs and was increased when exposed to 85 dB compared with 65
      dB. Exposure without earplugs to 85 dB but not to 65 dB increased heart rate.
      Heart rate and heart rate variability indicated increased sympathetic activation
      during the exposure to 85 dB compared with 65 dB. In general, behavioral and
      cardiac indicators did not indicate severe hearing impairment due to routine bell
      exposure. The 85-dB stimulus increased arousal and avoidance compared with the 65
      dB stimulus, with bell experience and earplugs leading to a general decrease in
      avoidance of the stimulus. This may reflect an altered acoustic perception of the
      playback stimulus in dairy cows that are routinely exposed to bells.

PMID- 29034248
TI  - Misoprostol Inhibits Equine Neutrophil Adhesion, Migration, and Respiratory Burst
      in an In Vitro Model of Inflammation.
AB  - In many equine inflammatory disease states, neutrophil activities, such as
      adhesion, migration, and reactive oxygen species (ROS) production become
      dysregulated. Dysregulated neutrophil activation causes tissue damage in horses
      with asthma, colitis, laminitis, and gastric glandular disease. Non-steroidal
      anti-inflammatory drugs do not adequately inhibit neutrophil inflammatory
      functions and can lead to dangerous adverse effects. Therefore, novel therapies
      that target mechanisms of neutrophil-mediated tissue damage are needed. One
      potential neutrophil-targeting therapeutic is the PGE1 analog, misoprostol.
      Misoprostol is a gastroprotectant that induces intracellular formation of the
      secondary messenger molecule cyclic AMP (cAMP), which has been shown to have anti
      inflammatory effects on neutrophils. Misoprostol is currently used in horses to
      treat NSAID-induced gastrointestinal injury; however, its effects on equine
      neutrophils have not been determined. We hypothesized that treatment of equine
      neutrophils with misoprostol would inhibit equine neutrophil adhesion, migration,
      and ROS production, in vitro. We tested this hypothesis using isolated equine
      peripheral blood neutrophils collected from 12 healthy adult teaching/research
      horses of mixed breed and gender. The effect of misoprostol treatment on
      adhesion, migration, and respiratory burst of equine neutrophils was evaluated
      via fluorescence-based adhesion and chemotaxis assays, and luminol-enhanced
      chemiluminescence, respectively. Neutrophils were pretreated with varying
      concentrations of misoprostol, vehicle, or appropriate functional inhibitory
      controls prior to stimulation with LTB4, CXCL8, PAF, lipopolysaccharide (LPS) or
      immune complex (IC). This study revealed that misoprostol pretreatment
      significantly inhibited LTB4-induced adhesion, LTB4-, CXCL8-, and PAF-induced
      chemotaxis, and LPS-, IC-, and PMA-induced ROS production in a concentration
      dependent manner. This data indicate that misoprostol-targeting of E-prostanoid
      (EP) receptors potently inhibits equine neutrophil effector functions in vitro.
      Additional studies are indicated to further elucidate the role of EP receptors in
      regulating neutrophil function. Overall, our results suggest misoprostol may hold
      promise as a novel anti-inflammatory therapeutic in the horse.

PMID- 29034250
TI  - The Modification and Performance of a Large Animal Anesthesia Machine
      (Tafonius(r)) in Order to Deliver Xenon to a Horse.
AB  - INTRODUCTION: Xenon, due to its interesting anesthetic properties, could improve
      the quality of anesthesia protocols in horses despite its high price. This study
      aimed to modify and test an anesthesia machine capable of delivering xenon to a
      horse. MATERIALS AND METHODS: An equine anesthesia machine (Tafonius, Vetronic
      Services Ltd., UK) was modified by including a T-connector in the valve block to
      introduce xenon, so that the xenon was pushed into the machine cylinder by the
      expired gases. A xenon analyzer was connected to the expiratory limb of the
      patient circuit. The operation of the machine was modeled and experimentally
      tested for denitrogenation, wash-in, and maintenance phases. The system was
      considered to consist of two compartments, one being the horse's lungs, the other
      being the machine cylinder and circuit. A 15-year-old, 514-kg, healthy gelding
      horse was anesthetized for 70 min using acepromazine, romifidine, morphine,
      diazepam, and ketamine. Anesthesia was maintained with xenon and oxygen, co
      administered with lidocaine. Ventilation was controlled. Cardiorespiratory
      variables, expired fraction of xenon (FeXe), blood gases were measured and xenon
      was detected in plasma. Recovery was unassisted and recorded. RESULTS: FeXe
      remained around 65%, using a xenon total volume of 250 L. Five additional boli of
      ketamine were required to maintain anesthesia. PaO2 was 45 +/- 1 mmHg. The
      recovery was calm. Xenon was detected in blood during the entire administration
      time. CONCLUSION: This pilot study describes how to deliver xenon to a horse.
      Although many technical problems were encountered, their correction could guide
      future endeavors to study the use of xenon in horses.

PMID- 29034251
TI  - Challenges in Decision Making in Elderly Patients with Gastrointestinal
      Malignancies.

PMID- 29034249
TI  - Misoprostol Inhibits Lipopolysaccharide-Induced Pro-inflammatory Cytokine
      Production by Equine Leukocytes.
AB  - Pro-inflammatory cytokines including tumor necrosis factor alpha (TNFalpha), IL
      1beta, IL-6, and IL-8 are potent immune mediators that exacerbate multiple equine
      diseases such as sepsis and laminitis. Unfortunately, safe and effective cytokine
      targeting therapies are lacking in horses; therefore, novel mechanisms of
      inhibiting cytokine production are critically needed. One potential mechanism for
      inhibiting cytokine synthesis is elevation of intracellular cyclic AMP (cAMP). In
      human leukocytes, intracellular cAMP production is induced by activation of E
      prostanoid (EP) receptors 2 and 4. These receptors can be targeted by the EP2/4
      agonist and prostaglandin E1 analog, misoprostol. Misoprostol is currently used
      as a gastroprotectant in horses but has not been evaluated as a cytokine
      targeting therapeutic. Thus, we hypothesized that misoprostol treatment would
      inhibit pro-inflammatory cytokine production by lipopolysaccharide (LPS)
      stimulated equine leukocytes in an in vitro inflammation model. To test this
      hypothesis, equine leukocyte-rich plasma (LRP) was collected from 12 healthy
      adult horses and used to model LPS-mediated inflammatory signaling. LRP was
      treated with varying concentrations of misoprostol either before (pretreated) or
      following (posttreated) LPS stimulation. LRP supernatants were assayed for 23
      cytokines using an equine-specific multiplex bead immunoassay. Leukocytes were
      isolated from LRP, and leukocyte mRNA levels of four important cytokines were
      evaluated via RT-PCR. Statistical differences between treatments were determined
      using one-way RM ANOVA (Holm-Sidak post hoc testing) or Friedman's RM ANOVA on
      Ranks (SNK post hoc testing), where appropriate (p < 0.05, n = 3-6 horses). These
      studies revealed that misoprostol pre- and posttreatment inhibited LPS-induced
      TNFalpha and IL-6 protein production in equine leukocytes but had no effect on IL
      8 protein. Interestingly, misoprostol pretreatment enhanced IL-1beta protein
      synthesis following 6 h of LPS stimulation, while misoprostol posttreatment
      inhibited IL-1beta protein production after 24 h of LPS stimulation. At the mRNA
      level, misoprostol pre- and posttreatment inhibited LPS-induced TNFalpha, IL
      1beta, and IL-6 mRNA production but did not affect IL-8 mRNA. These results
      indicate that misoprostol exerts anti-inflammatory effects on equine leukocytes
      when applied before or after a pro-inflammatory stimulus. However, the effects we
      observed were cytokine-specific and sometimes differed at the mRNA and protein
      levels. Further studies are warranted to establish the inhibitory effects of
      misoprostol on equine cytokine production in vivo.

PMID- 29034252
TI  - Age and Outcome in Gastrointestinal Cancers: A Population-Based Evaluation of
      Oesophageal, Gastric and Colorectal Cancer.
AB  - BACKGROUND: With demographic changes and partial representativeness of randomized
      studies the question arises which results are achieved in the treatment of the
      elderly. The objective was to analyse population-based data on gastrointestinal
      cancers in terms of age. METHODS: Analyses included data of the Munich Cancer
      Registry, i.e. 4,014, 10,127 and 42,809 invasive oesophageal, gastric and
      colorectal cancer patients, respectively, which were diagnosed between 1998 and
      2014. Tumour characteristics and outcome were analysed by age groups and therapy.
      Overall survival was analysed using the Kaplan-Meier method, and relative
      survival was computed as estimation for cancer-specific survival. Additionally,
      conditional survival of patients surviving at least 6 or 12 months was analysed
      by age. RESULTS: 21, 44 and 38% of oesophageal, gastric and colorectal cancer
      patients, respectively, were aged >75 years. Of these, 15, 46 and 73% were
      surgically treated with curative intent, respectively, which is significantly
      less than in younger patients. The total 5-year relative survival was 24, 33 and
      66%, respectively. The differences in median survival by age group were
      diminished by selecting those surviving at least 6 or 12 months and those with
      curatively intended treatment. CONCLUSION: An adequate patient selection for
      therapies of these gastrointestinal cancers was demonstrated at large. If the
      patients' general conditions allowed curatively intended treatment, it was
      applied and led to similar outcomes irrespective of age.

PMID- 29034253
TI  - Risk Factors for Adverse Outcome for Elderly Patients undergoing Curative
      Oncological Resection for Gastrointestinal Malignancies.
AB  - BACKGROUND: The incidence of gastrointestinal cancer increases with age, with
      approximately 20% of these cases in people over 80 years of age. Due to pre
      existing comorbidities, this onco-geriatric population often presents diagnostic
      and therapeutic challenges. METHODS: A systematic review of articles on PubMed
      was performed to determine the predictive ability of screening tools and their
      components regarding the occurrence of adverse outcomes in elderly onco-surgical
      patients with gastrointestinal malignancies. RESULTS: Surgical procedures in this
      patient cohort, particularly complex resections, may result in increased
      morbidity and mortality. The decision to treat an elderly patient with curative
      intent requires sound clinical judgment based on knowledge, consideration of
      objective parameters, and experience. These patients could potentially be
      optimized for surgery with the improvement of nutritional and overall performance
      status as well as with stabilizing comorbidities. CONCLUSION: Various geriatric
      assessment and screening tools have been developed to identify risk factors to
      assist the surgeon and the interdisciplinary team in treatment planning,
      including the Frailty Assessment Score, Timed Up and Go test, nutritional status,
      and Activities of Daily Living test. It is important to emphasize that
      transparent and open communication between the treating surgeon and the patient
      is crucial in that the patient fully understands the implications of the
      treatment plan.

PMID- 29034254
TI  - Attitudes of Surgeons toward Elderly Cancer Patients: A Survey from the SIOG
      Surgical Task Force.
AB  - Cancer care in elderly patients is complex. A recent survey showed that among
      mostly academic surgeons, practice patterns varied in the care of elderly
      patients. The authors suggested three areas of intervention in improving care of
      this population: frailty assessment, nutritional assessment, and assessment of
      quality of life.

PMID- 29034257
TI  - Challenges in Decision Making in Elderly Patients with Gastrointestinal
      Malignancies.

PMID- 29034256
TI  - Integration of Geriatric Assessment in the Care of Patients with Gastrointestinal
      Malignancies.
AB  - BACKGROUND: The majority of patients with gastrointestinal (GI) malignancies are
      older. Recently, it has become evident that elements from a geriatric assessment
      (GA) are powerful predictors of outcomes such as postoperative morbidity and
      mortality, length of stay, type of treatment received, and survival across
      several GI tumor types in older adults. A GA is a systematic evaluation of
      functional status, comorbidities, polypharmacy, cognition, nutritional status,
      emotional status, and social support. METHODS: A PubMed search was performed in
      order to identify clinical studies investigating the association between GA and
      outcomes in patients with GI malignancies. RESULTS: A total of 31 studies were
      included in this review. For colorectal cancer, the evidence linking GA variables
      and frailty to negative outcomes is substantial and consistent. The data
      regarding other GI malignancies is more limited, but generally shows the same
      findings. CONCLUSION: Increasing data shows that elements from a GA and frailty
      are consistently associated with negative short- and long-term treatment outcomes
      in older patients with GI malignancies. Future studies should investigate the
      impact of geriatric interventions on outcomes.

PMID- 29034255
TI  - Perioperative Management of Elderly Patients with Gastrointestinal Malignancies:
      The Contribution of Anesthesia.
AB  - INTRODUCTION: Elderly patients suffering from gastrointestinal malignancies are
      particularly prone to perioperative complications. Elderly patients often present
      with reduced physiological reserves, and comorbidities can limit treatment
      options and promote complications. Surgeons and anesthesiologists must be aware
      of strategies required to deal with this vulnerable subgroup. METHODS: We provide
      a brief review of current and emerging perioperative strategies for the treatment
      of elderly patients with gastrointestinal malignancies and frequent
      comorbidities. RESULTS: Especially in combination with advanced age, the effects
      of malignancies can be devastating, bringing new health challenges, exacerbating
      preexisting conditions, and exerting severe psychological strain. An
      interdisciplinary assessment and process planning provide an ideal setting to
      identify and prevent potential complications, especially in regards to frailty
      and cardiovascular risk. In addition, important perioperative considerations are
      presented, such as malnutrition, fasting, intraoperative neuromonitoring, and
      hemodynamic control, as well as postoperative early mobilization, pain, and
      delirium management. CONCLUSION: The decisions and interventions made in the
      perioperative stage can positively influence many intra- and postoperative
      factors, significantly improving the chances of successful treatment of elderly
      cancer patients. Appropriate management can help prevent or mitigate
      complications, secure a quick recovery, and improve short- and long-term
      outcomes.

PMID- 29034258
TI  - Migrants and Refugees in Europe: Challenges, Experiences and Contributions.
AB  - Due to the current geopolitical situation more refugees from crisis countries
      were and will be treated in Europe. In 2015 the number of displaced people
      reached an unprecedented level, with more than one million crossing into Europe.
      The migration itself can impair both mental and physical health. Therefore, the
      provision of medical care for refugees and migrants is a novel and major
      challenge for the health care systems in Europe. In this article we describe our
      experiences and contribution in providing medical care for refugees who have
      newly arrived in Stuttgart, Baden-Wuerttemberg, Germany. Furthermore, we report
      our experiences from a tertiary referral University center in Regensburg,
      Bavaria, Germany. We focus on challenges in both the outpatient and the inpatient
      setting, with a special focus on intensive care patients. In addition, we provide
      an overview about the spectrum of diseases in this specific patient cohort.

PMID- 29034259
TI  - Problem Adaptation Therapy for Pain (PATH-Pain): A Psychosocial Intervention for
      Older Adults with Chronic Pain and Negative Emotions in Primary Care.
AB  - Chronic pain is highly prevalent in older adults, contributes to activity
      restriction and social isolation, disrupts family and interpersonal
      relationships, and poses a significant economic burden to society. Negative
      emotions such as sadness, anxiety, helplessness, and hopelessness are associated
      with chronic pain and contribute to poor quality of life, impaired interpersonal
      and social functioning, and increased disability. Psychosocial interventions for
      older adults with chronic pain have been historically developed for, and are
      almost exclusively delivered to, cognitively intact patients. Therefore, many
      older adults with chronic pain and comorbid cognitive deficits have limited
      treatment options. Our multidisciplinary team developed Problem Adaptation
      Therapy for Pain in Primary Care (PATH-Pain), a psychosocial intervention for
      older adults with chronic pain, negative emotions, and a wide range of cognitive
      functioning, including mild-to-moderate cognitive impairment. In the current
      article, we describe the principles underlying PATH-Pain, review the steps taken
      to adapt the original PATH protocol, outline the treatment process, and present a
      case illustrating its potential value.

PMID- 29034260
TI  - Clodronate Improves Survival of Transplanted Hoxb8 Myeloid Progenitors with
      Constitutively Active GMCSFR in Immunocompetent Mice.
AB  - New methods to produce large numbers of myeloid progenitor cells, precursors to
      macrophages (MPhis), by maintaining Hoxb8 transcription factor activity1 has
      reinvigorated interest in MPhi cell therapies. We generated Hoxb8-dependent
      myeloid progenitors (HDPs) by transducing lineage-negative bone marrow cells with
      a constitutively expressed Hoxb8 flanked by loxP. HDPs proliferate indefinitely
      and differentiate into MPhi when Hoxb8 is removed by a tamoxifen-inducible Cre.
      We genetically modified HDPs with a constitutively active GMCSF receptor and the
      tamoxifen-induced transcription factor IRF8, which we have termed "HDP-on." The
      HDP-on proliferates without GMCSF and differentiates into the MPhi upon exposure
      to tamoxifen and ruxolitinib (GMCSF inhibitor via JAK1/2 blockade). We quantified
      the biodistribution of HDPs transplanted via intraperitoneal injection into
      immunodeficient NCG mice with a luciferase reporter; HDPs are detected for 14
      days in the peritoneal cavity, liver, spleen, kidney, bone marrow, brain, lung,
      heart, and blood. In immunocompetent BALB/c mice, HDP-on cells, but not HDPs, are
      detected 1 day post-transplantation in the peritoneal cavity. Pretreatment of
      BALB/c mice with liposomal clodronate significantly enhances survival at day 7
      for HDPs and HDP-on cells in the peritoneal cavity, spleen, and liver, but cells
      are undetectable at day 14. Short-term post-transplantation survival of HDPs is
      significantly improved using HDP-on and liposomal clodronate, opening a path for
      MPhi-based therapeutics.

PMID- 29034261
TI  - In Vivo Production of Monoclonal Antibodies by Gene Transfer via Electroporation
      Protects against Lethal Influenza and Ebola Infections.
AB  - Monoclonal antibodies (mAbs) have wide clinical utility, but global access is
      limited by high costs and impracticalities associated with repeated passive
      administration. Here, we describe an optimized electroporation-based DNA gene
      transfer platform technology that can be utilized for production of functional
      mAbs in vivo, with the potential to reduce costs and administration burdens. We
      demonstrate that multiple mAbs can be simultaneously expressed at protective
      concentrations for a protracted period of time using DNA doses and
      electroporation conditions that are feasible clinically. The expressed mAbs could
      also protect mice against lethal influenza or Ebola virus challenges. Our
      findings suggest that this DNA gene transfer platform technology could be a game
      changing advance that expands access to effective mAb therapeutics globally.

PMID- 29034262
TI  - Detection of Replication Competent Lentivirus Using a qPCR Assay for VSV-G.
AB  - Lentiviral vectors are a common tool used to introduce new and corrected genes
      into cell therapy products for treatment of human diseases. Although lentiviral
      vectors are ideal for delivery and stable integration of genes of interest into
      the host cell genome, they potentially pose risks to human health, such as
      integration-mediated transformation and generation of a replication competent
      lentivirus (RCL) capable of infecting non-target cells. In consideration of the
      latter risk, all cell-based products modified by lentiviral vectors and intended
      for patient use must be tested for RCL prior to treatment of the patient. Current
      Food and Drug Administration (FDA) guidelines recommend use of cell-based assays
      to this end, which can take up to 6 weeks for results. However, qPCR-based assays
      are a quick alternative for rapid assessment of RCL in products intended for
      fresh infusion. We describe here the development and qualification of a qPCR
      assay based on detection of envelope gene sequences (vesicular stomatitis virus G
      glycoprotein [VSV-G]) for RCL in accordance with Minimum Information for
      Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines. Our
      results demonstrate the sensitivity, linearity, specificity, and reproducibility
      of detection of VSV-G sequences, with a low false-positive rate. These procedures
      are currently being used in our phase 1 clinical investigations.

PMID- 29034263
TI  - Modeling Causal Relationships among Brain Areas in the Mesocorticolimbic System
      during Resting-State in Cocaine Users Utilizing a Graph Theoretic Approach.
AB  - OBJECTIVE: While effective connectivity (EC, causal interaction) between brain
      areas has been investigated in chronic users of cocaine as they view cocaine
      pictures cues, no study has examined EC while they take part in a resting-state
      scan. This resting-state fMRI study aims to investigate the causal interaction
      among brain areas in the mesocorticolimbic system (MCLS), which is involved in
      reward and motivation, in cocaine users (vs. controls). METHOD: Twenty cocaine
      users and 17 healthy controls finished a structural and a resting-state scan.
      Mean voxel-based time series data were obtained from brain regions of interest
      (ROIs) from the MCLS, and were input into a Bayesian search algorithm called
      IMaGES. RESULTS: The causal interaction pattern was different between the two
      groups. The feed-forward pattern found in cocaine smokers, between 7 ROIs of the
      MCLS during resting-state [ventral tegmental area (VTA)->hippocampus (HIPP)
      >ventral striatum (VenStri)->orbital frontal cortex (OFC), medial frontal cortex
      (MFC), anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC)],
      was absent in controls. That is, the subcortical VenStri area had a causal
      influence on four cortical brain areas only in cocaine users. CONCLUSIONS: During
      the resting-state scan, the VTA of cocaine smokers abstinent for at least 72
      hours, but not controls, begins causal connections to limbic, midbrain, and
      frontal regions in the MCLS in a feed-forward manner. Following replication,
      further studies may assess if changes over time in EC during resting-state
      predict cocaine treatment efficacy and outcome.

PMID- 29034265
TI  - Coupled Bimanual Training Using a Non-Powered Device for Individuals with Severe
      Hemiparesis: A Pilot Study.
AB  - BACKGROUND: Few options exist for training arm movements in participants with
      severe post-stroke hemiparesis who have little active range of motion. The
      purpose of this study was to test the safety and feasibility of training with a
      non-powered device, the Bimanual Arm Trainer (BAT), to facilitate motor recovery
      in individuals with severe hemiparesis. The BAT enabled coupled bimanual training
      of shoulder external rotation, which is reduced in individuals with severe post
      stroke hemiplegia. The rationale for bimanual training was to harness
      contralesional cortical activity to drive voluntary movement in the affected arm
      in patients who could barely perform unimanual movements. METHODS: Nine
      participants with post-stroke hemiparesis, preserved passive range of motion and
      Modified Ashworth score of <3 in the shoulder and elbow joints, trained with the
      device for 45 minutes, twice a week for six weeks, and were assessed pre- and
      post-training. RESULTS: All participants tolerated the training and no adverse
      events were reported. Participants showed significant improvement in the upper
      extremity Fugl-Meyer score post-training with an effect size of 0.89. Changes in
      the flexor synergy pattern accounted for 64.7% of the improvement. Improvement in
      active range of motion in the paretic limb occurred for both trained and
      untrained movements. Some participants showed improvement in the time taken to
      perform selected tasks on the Wolf Motor Function Test post-training. CONCLUSION:
      The results demonstrate the safety and feasibility of using the Bimanual Arm
      Trainer to facilitate motor recovery in individuals with severe hemiparesis.

PMID- 29034266
TI  - Bladder pain in an LL-37 interstitial cystitis and painful bladder syndrome
      model.
AB  - Our goal was to evaluate the pain response in an LL-37 induced murine model for
      interstitial cystitis/painful bladder syndrome (IC/PBS). In particular, we sought
      to characterize the dose dependence, time-course, and relationship of LL-37
      induced bladder inflammation and pain. The IC/PBS model was induced in C57Bl/6
      mice by instilling 50 MUL of LL-37, an immunomodulatory human cathelicidin (anti
      microbial peptide), in the bladder for 1 hr. Pain responses were measured using
      von Frey filaments (0.04 gm to 4.0 gm) before and after LL-37 instillation.
      Inflammation was evaluated using tissue myeloperoxidase (MPO) assay, gross
      inspection, and microscopic histologic examination. The dose response experiment
      demonstrated a graded pain response, with higher concentrations of LL-37
      challenge yielding higher pain responses across all stimuli tested. Statistical
      significance was seen when comparing 1.0 gm von Frey filament results at 320 MUM
      (68 +/- 8% response) vs. 0 MUM (38 +/- 6% response). Interestingly, pain
      responses did not attenuate across time but increased significantly after 5
      (p=0.0012) and 7 days (p=0.0096). Comparison with MPO data suggested that pain
      responses could be independent of inflammation. We demonstrated within our LL-37
      induced IC/PBS model pain occurs in a dose-dependent fashion, pain responses
      persist beyond the initial point of insult, and our dose response and time course
      experiments demonstrated that pain was independent of inflammation.

PMID- 29034264
TI  - Reducing Cardiac Fibrosis: Na/K-ATPase Signaling Complex as a Novel Target.
AB  - Cardiac fibrosis is a common pathological process in cardiac disease and may lead
      to heart failure. It can also cause sudden death even in those without cardiac
      symptoms. Tissue fibrosis can be categorized into two categories: replacement
      fibrosis (also called reparative fibrosis) and reactive fibrosis. In replacement
      fibrosis, infiltration of inflammatory cells and accumulation of Extracellular
      Matrix (ECM) proteins are the initial steps in forming scarlike fibrotic tissue
      after acute cardiac injury and cardiac cell necrosis. Reactive fibrosis can be
      formed in response to hormonal change and pressure or volume overload.
      Experimental studies in animals have identified important pathways such as the
      Renin-Angiotensin-Aldosterone System (RAAS) and the endothelin pathway that
      contribute to fibrosis formation. Despite the fact that clinical trials using
      RAAS inhibitors as therapies for reducing cardiac fibrosis and improving cardiac
      function have been promising, heart failure is still the leading cause of deaths
      in the United States. Intensive efforts have been made to find novel targets and
      to develop new treatments for cardiac fibrosis and heart failure in the past few
      decades. The Na/K-ATPase, a canonical ion transporter, has been shown to also
      function as a signal transducer and prolonged activation of Na/K-ATPase signaling
      has been found to promote the formation of cardiac fibrosis. Novel tools that
      block the activation of Na/K-ATPase signaling have been developed and have shown
      promise in reducing cardiac fibrosis. This review will discuss the recent
      development of novel molecular targets, focusing on the Na/K-ATPase signaling
      complex as a therapeutic target in treatment of cardiac fibrosis.

PMID- 29034267
TI  - Spectral CT Reconstruction with Image Sparsity and Spectral Mean.
AB  - Photon-counting detectors can acquire x-ray intensity data in different energy
      bins. The signal to noise ratio of resultant raw data in each energy bin is
      generally low due to the narrow bin width and quantum noise. To address this
      problem, here we propose an image reconstruction approach for spectral CT to
      simultaneously reconstructs x-ray attenuation coefficients in all the energy
      bins. Because the measured spectral data are highly correlated among the x-ray
      energy bins, the intra-image sparsity and inter-image similarity are important
      prior acknowledge for image reconstruction. Inspired by this observation, the
      total variation (TV) and spectral mean (SM) measures are combined to improve the
      quality of reconstructed images. For this purpose, a linear mapping function is
      used to minimalize image differences between energy bins. The split Bregman
      technique is applied to perform image reconstruction. Our numerical and
      experimental results show that the proposed algorithms outperform competing
      iterative algorithms in this context.

PMID- 29034268
TI  - Language Emergence.
AB  - Language emergence describes moments in historical time when nonlinguistic
      systems become linguistic. Because language can be invented de novo in the manual
      modality, this offers insight into the emergence of language in ways that the
      oral modality cannot. Here we focus on homesign, gestures developed by deaf
      individuals who cannot acquire spoken language and have not been exposed to sign
      language. We contrast homesign with (a) gestures that hearing individuals produce
      when they speak, as these cospeech gestures are a potential source of input to
      homesigners, and (b) established sign languages, as these codified systems
      display the linguistic structure that homesign has the potential to assume. We
      find that the manual modality takes on linguistic properties, even in the hands
      of a child not exposed to a language model. But it grows into full-blown language
      only with the support of a community that transmits the system to the next
      generation.

PMID- 29034269
TI  - The Role of Botulinum Toxin A in Treatment of Temporomandibular Joint Disorders:
      A Review.
AB  - Temporomandibular joint disorders (TMDs) usually present with symptoms and signs
      such as pain, mandibular movement, dysfunction, or joint sounds. Botulinum toxin
      type A (BTX-A) is a biologic toxin which inhibits skeletal muscle through
      hindering the production of acetylcholine in the nerve endings. This toxin is
      used for the treatment of hyperactivity of lateral pterygoid muscle and TMD
      symptoms. This comprehensive review aimed to evaluate the effect of BTX-A
      injections in the lateral pterygoid muscle on treatment of TMDs symptoms. In this
      study, online databases including Scopus, Medline, Ebsco, Cochrane, EMBASE, and
      Google scholar were searched for the keywords "pterygoid muscle" and
      "Onabotulinumtoxin A". Twenty-four articles were eligible to be enrolled in the
      study. In 4 interventional studies and 20 descriptive studies, BTX-A was used for
      the treatment of TMDs. The dosage and number of injections were different in each
      study; however, the injection methods were relatively similar. Regardless of the
      type, number of injections, and dosage, injection of BTX-A in lateral pterygoid
      seems effective in reducing the click sound and other TMJ-related muscle
      disorders such as pain, hyperactivity, and dysfunction.

PMID- 29034270
TI  - Clinical Evaluation of Effects of Local Application of Aloe vera Gel as an
      Adjunct to Scaling and Root Planning in Patients with Chronic Periodontitis.
AB  - STATEMENT OF THE PROBLEM: Aloe vera gel contains various components with
      antibiotic and anti-inflammatory characteristics, which may have potential
      advantages to treat periodontal diseases. PURPOSE: The aim of this study was to
      evaluate the effects of local application of aloe vera gel as an adjunct to
      scaling and root planning in the treatment of patients with chronic
      periodontitis. MATERIALS AND METHOD: This single-blind clinical trial, performed
      in a split mouth design, was conducted on 20 patients with moderate to severe
      chronic periodontitis. Following a baseline examination at first day which
      included the assessments of plaque index (PI), gingival index (GI), and probing
      depth (PD); patients randomly received either SRP in one quadrant (control
      group), or SRP combined with aloe vera gel in another quadrant (experimental
      group). All cases were examined again, assessing PI, GI, and PD at 30th and 60th
      day. RESULTS: There was no significant difference in PI in the three stages
      between control and experimental groups. In all patients, there was a significant
      improvement in the three stages in GI and PD for both quadrants treated only with
      SRP or combination of SRP and aloe vera. However, experimental group presented
      significantly lower GI (p= 0.0001) and PD (p= 0.009) than the control group at
      the end of study period. CONCLUSION: This study revealed that local application
      of aloe vera gel could be considered as an adjunctive treatment with scaling and
      root planning for chronic periodontitis.

PMID- 29034271
TI  - Effect of Propolis Extract in Combination with Eugenol-Free Dressing (Coe-PakTM)
      on Pain and Wound Healing after Crown-Lengthening: A Randomized Clinical Trial.
AB  - STATEMENT OF THE PROBLEM: Researchers have long been in search of products to
      enhance healing and patient comfort postoperatively. PURPOSE: This study aimed to
      assess the efficacy of propolis extract in combination with Coe-PakTM dressing
      for pain relief and wound healing after crown lengthening surgery. MATERIALS AND
      METHOD: This randomized clinical trial was performed on 36 patients who were
      randomly divided into two groups of Coe-PakTM dressing with (trial group) and
      without (control group) propolis extract. Pain and burning sensation by use of
      visual analog scale (VAS) and number of analgesics taken were asked from
      patients. Gingival color and consistency, bleeding on probing (BOP) and presence
      of infection were studied 7 days after dressing removal. RESULTS: Although a
      large number of patients in the trial group did not have burning sensation, this
      difference was not significant between the two groups (p> 0.05). In both groups,
      the majority of patients experienced moderate and mild pain and there was no pain
      in the trial group after three days. No significant difference was noted between
      the two groups in pain score and number of analgesics taken (p> 0.05). The two
      groups were not significantly different in terms of inflammation and healing
      process (BOP, gingival consistency and color), after 7 days (p> 0.05).
      CONCLUSION: The study results showed no difference in use of Coe-PakTM dressing
      with and without propolis extract in terms of postoperative pain and healing
      process following the crown lengthening surgery. More studies are required to
      confirm these results.

PMID- 29034272
TI  - Influence of Head Position on the CBCT Accuracy in Assessment of the Proximity of
      the Root Apices to the Inferior Alveolar Canal.
AB  - STATEMENT OF THE PROBLEM: The most important risk factor for inferior alveolar
      nerve (IAN) damage is the proximity of the mandibular root apices to the alveolar
      canal. Failure to position the patient's head at standardized orientation during
      cone beam computed tomography (CBCT) scans might adversely affect the relative
      position of the alveolar canal and mandibular root apices with subsequent
      treatment failure. PURPOSE: The purpose of the present study was to investigate
      the influence of the orientations of the skull during the scanning procedure on
      the accuracy of CBCT images in determining the positional relationship of the
      mandibular tooth apices to the alveolar canal. MATERIALS AND METHOD: CBCT scans
      of 7 human dry skulls were obtained by using NewTom VGi CBCT in standard, tilt,
      flexion, extension and rotation positions of the head. The shortest radiographic
      distance between the mandibular tooth apices and the IAN canal of 20 points were
      measured on cross sectional images of CBCT in all position scans. A sample t-test
      was used to compare the measurements at different head position with the standard
      position values. RESULTS: Significant differences were found in the measurements
      of normal and tilt orientations. However, there was no statistically significant
      difference between the measurements in standard position and other deviated
      positions. The mean errors in all head positions were less than 0.5mm.
      CONCLUSION: Alteration of patient head positioning during CBCT scanning does not
      affect the relative position of the IAN and the apices of posterior teeth.

PMID- 29034273
TI  - Comparison of the Effects of Transcutaneous Electrical Nerve Stimulation and Low
      Level Laser Therapy on Drug-Resistant Temporomandibular Disorders.
AB  - STATEMENT OF THE PROBLEM: Temporomandibular disorder (TMD) is a clinical term
      used for clinical signs and symptoms that affect the temporomandibular joints,
      masticatory muscles, and associated structures. Surgical and non-surgical
      treatments can be used for management of TMD. Non-surgical route is the main part
      of the treatment, since clinicians prefer non-aggressive treatment for TMD such
      as pharmacological and physical therapy. Low-level laser therapy (LLLT) and
      transcutaneous electrical nerve stimulation (TENS) are the main procedures in
      physical therapy. PURPOSE: The aim of this study was to evaluate the
      effectiveness of TENS and LLLT in treatment of TMD patients who did not respond
      to pharmacological therapy. MATERIALS AND METHOD: This clinical trial was
      performed on 45 patients who randomly received either TENS or LLLT for 8
      sessions. LLLT was applied with diode laser (Ga-Al-As, 980nm, dose 5j/cm2) and
      TENS by using two carbon electrodes with 75 Hz frequency (0.75 msec pulse width).
      Helkimo index and visual analogue scale (VAS) were measured during the treatment
      period and throughout the follow-up sessions. RESULTS: Significant reduction in
      the VAS and Helkimo index was observed in both TENS and LLLT group. There was no
      significant difference between the two methods during the treatment; however,
      TENS was more effective in pain reduction in follow-ups. CONCLUSION: This study
      justified the use of TENS therapy as well as LLLT in drug-resistant TMD. Both
      were useful in relieving the pain and muscles tenderness, although, TENS was more
      effective than LLLT.

PMID- 29034274
TI  - Prevalence and Characteristics of Developmental Dental Anomalies in Iranian
      Orofacial Cleft Patients.
AB  - STATEMENT OF THE PROBLEM: Individuals with oral clefts exhibit considerably more
      dental anomalies than individuals without clefts. These problems could initially
      be among the symptoms of their disease and/or they may be the side effect of
      their treatments. Pushback palatoplasty could cause some interference during the
      development of teeth and result in tooth defects. PURPOSE: The study was
      performed to assess the prevalence and characteristics of developmental dental
      anomalies in orofacial cleft patients who attended Shiraz Orthodontics Research
      Center-Cleft Lip and Palate Clinic. We managed to compare dental anomaly traits
      based on gender and cleft side. MATERIALS AND METHOD: Eighty out of 121 cleft
      patients were included in this cross-sectional study. All the patients used
      pushback palatoplasty in their palate closure surgeries. Intraoral photographs,
      panoramic and intraoral radiographs, cone-beam computed tomography (CBCT) and
      dental and medical histories were examined and recorded by two observers. Data
      were analyzed using SPSS PC version 20.0. The differences in the side of cleft
      and dental anomalies were compared using the Mann-Whitney test. RESULTS: The mean
      age of patients was 14.27 years (SD=5.06). The most frequent cleft type was
      unilateral cleft lip and palate (50%) followed by bilateral cleft lip and palate
      (43.75%), cleft palate (2.5%) and cleft lip (1.25%). Male predominance (70%) was
      observed. 92.5 percent had at least one developmental dental anomaly. The most
      prevalent anomalies were hypodontia (71.25%) followed by microdontia (30%), root
      dilacerations (21.25%) and supernumerary teeth (15%). CONCLUSION: The most
      prevalent cleft types were unilateral and bilateral cleft lip and palate with
      male and left side predominance. Hypodontia, microdontia, dilacerations and
      supernumerary teeth were the most prevalent developmental dental anomalies among
      Iranian southwestern cleft patients. The surgical technique used to repair their
      cleft palate may have played a role in developmental dental defects.

PMID- 29034275
TI  - Diagnosis of Approximal Caries after Delayed Scanning of Photostimulable Phosphor
      Plates.
AB  - STATEMENT OF THE PROBLEM: Considering the high diagnostic accuracy and wide
      dynamic range of photostimulable phosphor plates (PSPs), they can be a good
      alternative for radiographic films. PURPOSE: This study was aimed to assess the
      effects of delay in scanning PSPs on the diagnostic accuracy of detection of
      approximal caries. MATERIALS AND METHOD: Radiographs from fifty-two extracted
      molar and premolar teeth were radiographed using DIGORA PSP (Soredex Corporation,
      Helsinki, Finland). The teeth were either intact or with non-cavitated approximal
      caries. The plates were scanned immediately (time zero) and at 10 min, 30 min, 60
      min and 120 min after exposure. Sixty-five images were obtained and evaluated for
      presence or absence of approximal caries by two oral and maxillofacial
      radiologists and 2 restorative specialists. The diagnostic accuracy of approximal
      caries detection was measured using a 5-point rating scale. Definite presence of
      caries was confirmed using a stereomicroscope. Analysis of caries detection data
      was performed by calculating sensitivity and specificity using repeated measures
      with ANOVA. RESULTS: Significant differences were found in complete negative
      predictive value, absolute negative predictive value and complete dentine
      sensitivity value between different scan times (p< 0.05). These values were
      significantly different at 10 min, 60 min and 120 min (p< 0.05). However,
      immediate scan and 30 min delay were not significantly different (p> 0.05). The
      accuracy of approximal caries detection at 120 min was less than at 60 min and at
      60 min was less than at 30 min. CONCLUSION: In order to detect approximal caries
      more accurately, DIGORA PSPs should be scanned within 30 min after exposure.

PMID- 29034276
TI  - Evaluation of the Ki-67 and MCM3 Expression in Cytologic Smear of Oral Squamous
      Cell Carcinoma.
AB  - STATEMENT OF THE PROBLEM: Squamous cell carcinoma (SCC) is the most frequent oral
      cancer whose 5-year survival rate is 80% for early-detected lesions and nearly 30
      50% for advanced lesions. Early detection of oral cancers and precancerous
      lesions can improve the patient's survival and decrease the morbidity. PURPOSE:
      This study aimed to evaluate and compare the Ki-67 and MCM3 expression in
      cytologic smear of oral SCC (OSCC). MATERIALS AND METHOD: We examined 48 oral
      brush biopsies including 28 OSCC and 20 healthy non-smoking samples.
      Immunocytochemistry staining was performed for Ki-67 and MCM3 by using an
      EnVision-labeled peroxidase system, and labeling index (LI) was calculated.
      RESULTS: Out of 28 OSCC cases, 27(96.4%) cases contained MCM3 positive cells and
      22(78%) cases contained Ki-67 positive cells. All normal mucosa were Ki-67 and
      MCM3 negative. MCM3 and Ki-67 LI were significantly higher in OSCC than normal
      mucosa (p< 0.001). MCM3 LI was significantly higher than Ki-67 LI in OSCC group
      (p< 0.001). CONCLUSION: Immunocytologic evaluation of Ki-67 and MCM3 can be used
      for early detection of OSCC. Furthermore, MCM3 may be a more sensitive cytologic
      biomarker than Ki-67 in SCC patients.

PMID- 29034277
TI  - Knowledge and Attitudes of Elementary Schoolteachers on Dental Trauma and its
      Management in Yazd, Iran.
AB  - STATEMENT OF THE PROBLEM: School is one of the places with the greatest
      prevalence of occurrence of traumatic dental injuries. PURPOSE: The aim of this
      study was to assess the knowledge levels and attitudes of elementary school
      teachers towards dental trauma and its management. MATERIALS AND METHOD: In this
      cross-sectional study, 281 elementary school teachers were selected through
      cluster sampling to answer the prepared questionnaire. The data obtained from the
      questionnaires were analyzed in SPSS software by using ANOVA test and t-test. p
      Value<0.05 was considered to be significant. RESULTS: The total knowledge and
      attitude were low and normal, respectively. No previous exposure to or close
      observation of a dental trauma was reported by 61.2% of teachers; while, 12.5%
      were trained on dental traumas first aid management. There was statistically
      significant relationship between the teacher's knowledge and previous first aids
      training. CONCLUSION: The knowledge of schoolteachers on emergency management of
      dental trauma is poor. Therefore, it seems to be helpful to consider the
      management of dental injuries especially avulsed teeth as a part of teachers'
      education.

PMID- 29034278
TI  - Cytotoxic Effect of Thiabendazole on Hn5 Head and Neck Squamous Cell Carcinoma
      Cell Line.
AB  - STATEMENT OF THE PROBLEM: Evidence shows thiabendazole has the potential to
      inhibit angiogenesis in melanoma and fibrosarcoma; however, its effect on oral
      squamous cell carcinoma has not been previously studied. PURPOSE: This study
      sought to assess the cytotoxic effects of thiabendazole on HN5 head and neck
      squamous carcinoma cell line. MATERIALS AND METHOD: HN5 cell lines were exposed
      to different concentrations of thiabendazole (prepared from 99% pure powder) for
      24, 48 and 72 hours. Cell viability was assessed by the methyl thiazol
      tetrazolium assay, and IC50 of thiabendazole was calculated. Cells were also
      exposed to different concentrations of thiabendazole for 48 hours to determine
      its effect on expression and transcription of vascular endothelial growth factor
      gene. Expression of vascular endothelial growth factor mRNA was assessed by real
      time polymerase chain reaction. The vascular endothelial growth factor release
      was assessed by the enzyme-linked immunosorbent assay test. RESULTS: In all
      concentrations of thiabendazole except for 200 and 550MUM, cell viability was
      significantly different at different time points (p< 0.05). At 48 and 72 hours,
      cell viability at all concentrations of thiabendazole (100-650MUM) significantly
      decreased compared to the control group (zero concentration). In addition, cell
      viability significantly decreased with an increase in thiabendazole
      concentration. At 48 hours, expression of vascular endothelial growth factor mRNA
      was significantly lower in presence of 500MUM thiabendazole compared to the
      control group (p< 0.001) and release of vascular endothelial growth factor was
      inhibited in a dose-dependent manner. CONCLUSION: Thiabendazole inhibited the
      proliferation of HN5 cells in a dose-dependent and time-dependent manner. It also
      inhibited the expression of vascular endothelial growth factor gene.

PMID- 29034279
TI  - Rare and Extensive Malignant Melanoma of the Oral Cavity: Report of Two Cases.
AB  - Primary oral melanomas are uncommon malignant neoplasm of melanocytes origin. The
      most common site of oral melanoma is maxillary gingiva and hard palate. Oral
      mucosal melanoma exhibit a pathobiological behavior and clinical features
      different from cutaneous melanomas. Oral melanomas are often clinically silent
      which may consequently result in delayed diagnosis; thus, making the prognosis
      extremely poor. This case report presents clinical, histopathological and
      immunohistochemical features of two cases of advanced oral melanoma, one
      pigmented or melanotic melanoma in a 46-year-old female and another amelanotic
      melanoma in a 59-year-old male patient, with chief complaint of swelling in oral
      mucosa. Most oral melanomas are usually asymptomatic lesions with quick growing.
      Thus, the most cases are detected in late stage of diagnosis. Early diagnosis
      with careful examination by dentists, and early biopsy of pigmented and
      suspicious non-pigmented lesions would have an imperative role in more survival
      rate and better prognosis.

PMID- 29034280
TI  - Ameloblastic Fibro-Odontoma in a 7-Month-Old Infant: A Case Report.
AB  - Ameloblastic fibro-odontoma is a relatively rare, benign odontogenic tumor that
      usually occurs in children and adolescents with unerupted teeth. This article
      reports an ameloblastic fibro-odontoma in the anterior mandible as a "bump on her
      gum" in a 7-month-old girl. This is the first case under 9 months old reported to
      date. Radiographic and histologic findings as well as the treatment are
      discussed.

PMID- 29034281
TI  - Systematic review of the safety and efficacy of contrast injection via venous
      catheters for contrast-enhanced computed tomography.
AB  - OBJECTIVE: To examine the safety and efficacy of contrast injection through a
      central venous catheter (CVC) for contrast-enhanced computed tomography (CECT).
      METHODS: A systematic literature search was performed using PubMed. Studies were
      deemed eligible if they reported on the use of CVCs for contrast administration.
      Selected articles were assessed for their relevance and risk of bias. Articles
      with low relevance and high risk of bias or both were excluded. Data from
      included articles was extracted. RESULTS: Seven studies reported on the use of
      CVCs for contrast administration. Catheter rupture did not occur in any study.
      The incidence of dislocation ranged from 2.2-15.4%. Quality of scans was
      described in three studies, with less contrast enhancement of pulmonary arteries
      and the thoracic aorta in two studies, and average or above average quality in
      one study. Four other studies used higher flowrates, but did not report quality
      of scans. CONCLUSION: Contrast injection via CVCs can be performed safely for
      CECT when using a strict protocol. Quality of scans depended on multiple factors
      like flow rate, indication of the scan, and cardiac output of the patient. In
      each patient, an individual evaluation whether to use the CVC as access for
      contrast media should be made, while bolus tracking may be mandatory in most
      cases.

PMID- 29034282
TI  - Differentiation of prostate cancer lesions in the Transition Zone by diffusion
      weighted MRI.
AB  - OBJECTIVE: To differentiate prostate cancer lesions in transition zone by
      diffusion-weighted-MRI (DW-MRI). METHODS: Data from a total of 63 patients who
      underwent preoperative DWI (b of 0-1000 s/mm2) were prospectively collected and
      processed by a monoexponential (DWI) model and compared with a biexponential
      (IVIM) model for quantitation of apparent diffusion coefficients (ADCs),
      perfusion fraction f, diffusivity D and pseudo-diffusivity D*. Histogram analyses
      were performed by outlining entire-tumor regions of interest (ROIs). These
      parameters (separately and combined in a logistic regression model) were used to
      differentiate lesions depending on histopathological analysis of Magnetic
      Resonance/transrectal Ultrasound (MR/TRUS) fusion-guided biopsy. The diagnostic
      ability of differentiate the PCa from BHP in TZ was analyzed by ROC regression.
      Histogram analysis of quantitative parameters and Gleason score were assessed
      with Spearman correlation. RESULTS: Thirty (30 foci) cases of PCa in PZ and 33
      (36 foci) cases of BPH were confirmed by pathology. Mean ADC, median ADC, 10th
      percentile ADC, 90th percentile ADC, kurtosis and skewness of ADC and mean D
      values, median D and 90th percentile D differed significantly between PCa and BHP
      in TZ. The highest classification accuracy was achieved by the mean ADC (0.841)
      and mean D (0.809). A logistic regression model based on mean ADC and mean D led
      to an AUC of 0.873, however, the difference is not significant. There were 7
      Gleason 6 areas, 9 Gleason 7 areas, 8 Gleason 8 areas, 5 Gleason 9 areas and 2
      Gleason 10 areas detected from the 31 prostate cancer areas, the mean Gleason
      value was(7.5 +/- 1.2). The mean ADC and mean D had correlation with Gleason
      score(r = -0.522 and r = -0.407 respectively, P < 0.05). CONCLUSION: The
      diagnosis efficiency of IVIM parameters was not superior to ADC in the diagnosis
      of PCa in TZ. Moreover, the combination of mean ADC and mean D did not perform
      better than the parameters alone significantly; It is feasible to stratify the
      pathological grade of prostate cancer by mean ADC.

PMID- 29034283
TI  - Endovenous laser ablation of spermatic vein for the treatment of varicocele.
AB  - INTRODUCTION: Varicocele is a relatively complex pathology of the scrotum veins',
      known to be one of the easiest to treat. Modern treatment involves both surgical
      (open, laparoscopic and microsurgery) and interventional approach (either with
      coils and/or sclerosant injection). Our aim is to demonstrate the feasibility and
      the reliability of endovenous laser ablation (EVLA) of the spermatic vein for the
      treatment of varicocele. MATERIALS AND METHODS: We consecutively and
      prospectively treated 11 patients (age range 24-45 years old, mean 31y) with left
      varicocele, phlebografically classified as Bahren type I and with indication for
      percutaneous treatment. Clinical success was evaluated by color doppler
      ultrasound (CDUS) one week, one months and three months after the procedures. We
      also evaluated the pain feeling for 48 h after the procedure on the basis of the
      visual analogue score (VAS) obtained through telephonic interview. RESULTS:
      Technical success was achieved in all cases. In all cases varicocele disappeared
      at CDUS at 1 and three months with reflux abolition. Two cases of small vein
      laceration were noted without sequelae, no other complication has been described.
      All patients reported improvements either regarding symptoms and/or
      spermiographic parameters. CONCLUSIONS: In our experience, EVLA of spermatic vein
      is a feasible and safe treatment in patients with Bahren type I varicocele. The
      key advantage of this technique is the adoption of a standardized protocol, which
      remains one of the main problems in gaining scientific evidence in case of coil
      or sclerosant embolisation (type and number of coils, amount of sclerosant agent
      etc).

PMID- 29034284
TI  - Data from roadside screening for psychoactive substances, alcohol and illicit
      drugs, among Spanish drivers in 2015.
AB  - The data presented in this article are related to the paper "Prevalence of
      psychoactive substances, alcohol and illicit drugs, in Spanish drivers: A
      roadside study in 2015". (https://doi.org/10.1016/j.forsciint.2017.07.005)
      Domingo-(Salvany et al., 2017) [1]. In that paper it was not possible to directly
      compare 2015 results with previous editions for various reasons, one of which was
      the lack of a similar weighting procedure. The present paper provides 2015
      figures of roadside screening tests which are weighted for traffic flow intensity
      and therefore allow direct comparisons with the screening tests conducted among
      Spanish drivers in 2008 and 2013.

PMID- 29034285
TI  - Data on chow, liver tissue and mitochondrial fatty acid compositions as well as
      mitochondrial proteome changes after feeding mice a western diet for 6-24 weeks.
AB  - The data presented in this article describe the fatty acid composition of chow,
      liver tissue and isolated liver mitochondria from mice fed for 6-24 weeks with a
      high caloric western diet (WD) in comparison to control diet (normal diet, ND).
      The fatty acid composition was measured via gas chromatography flame ionization
      detection (GC-FID). Moreover, WD-induced mitochondrial protein changes are
      presented in this work and were analyzed by mass spectrometry (LC-MS/MS). For
      further interpretation and discussion of the presented data please refer to the
      research article entitled "Mitochondrial adaptation in steatotic mice" (Einer et
      al., 2017) [1].

PMID- 29034286
TI  - Data of indirect immunofluorescence labeling of the mouse brain sections with
      sera from SLE and MS patients.
AB  - The data presented in this article are related to the research article entitled
      "Behcet Disease serum is immunoreactive to neurofilament medium which share
      common epitopes to bacterial HSP-65, a putative trigger" (Lule et a. 2017) [1].
      The immunoreactivity to self-antigens is well characterized for systemic lupus
      erythematosus (SLE) and multiple sclerosis (MS) (Magro Checa et al., 2013) [2].
      Indirect immunofluorescence labeling of the mouse tissue sections with patient
      sera has recently been popular to discover novel epitopes and gain mechanistic
      insight to diseases with dysregulated immunity (Lennon et al., 2004) [3]. The
      present article demonstrates widespread labeling of cell nuclei with SLE patient
      sera and sporadic filamentous labeling along the axons with MS patient sera on
      mouse brain sections. The filamentous immunolabeling was sometimes associated
      with cytoplasmic staining of cells, which sent processes along the axon bundles,
      suggesting that they were oligodendrocytes. Since the mouse brain tissue has
      little autofluorescence and limited connective tissue causing non-specific
      immunolabeling, it appears superior to peripheral tissues for searching serum
      immunoreactivity.

PMID- 29034287
TI  - Numerical data concerning wind farm layout optimization using differential
      evolution algorithm at different wind speeds.
AB  - In this work, the numerical data related to wind turbine micrositing problem is
      presented. The data is acquired using the differential evolution algorithm (DEA)
      at different wind speeds. The data obtained through DEA include total dissipated
      power, cost per installation of unit turbine, and the efficiency of algorithm
      after installation of any particular number turbines; and are depicted versus
      number of turbines. The data provided in this paper can be used directly without
      having to spend weeks of computational time to simulate the results; and can
      readily be used for comparison with other existing (Massan et al. [1] and Rajper
      et al. [2], etc.) and forthcoming algorithms in future.

PMID- 29034288
TI  - The TNO Multiband Image Data Collection.
AB  - Despite of the ongoing interest in the fusion of multi-band images for
      surveillance applications and a steady stream of publications in this area, there
      is only a very small number of static registered multi-band test images (and a
      total lack of dynamic image sequences) publicly available for the development and
      evaluation of image fusion algorithms. To fill this gap, the TNO Multiband Image
      Collection provides intensified visual (390-700 nm), near-infrared (700-1000 nm),
      and longwave infrared (8-12 um) nighttime imagery of different military and
      surveillance scenarios, showing different objects and targets (e.g., people,
      vehicles) in a range of different (e.g., rural, urban) backgrounds. The dataset
      will be useful for the development of static and dynamic image fusion algorithms,
      color fusion algorithms, multispectral target detection and recognition
      algorithms, and dim target detection algorithms.

PMID- 29034289
TI  - Optical and electrical properties of the nanodisk-shaped SnS layers grown by
      sputtering.
AB  - In this data article, we presented the structural, optical, and electrical data
      of the nanodisk-shaped SnS layers. A facile formation of orthorhombic SnS derived
      from SnS2 particles was discussed in our previous study (Patel et al., 2017) [1].
      The data includes the standard XRD patterns supercell structure of the
      Orthorhombic SnS material, the photograph of prepared samples, thickness
      dependent absorbance spectra, and temperature dependent carrier concentration and
      its mobility estimated from the hall measurement of SnS samples.

PMID- 29034291
TI  - Microbial biodiversity of Tang and Pirgal mud volcanoes and evaluation of bio
      emulsifier and bio-demulsifier activities of Capnophile bacteria.
AB  - The data presented in this article is related to the Master thesis; entitled
      "Survey Aerobic Microbial Diversity Mud Volcanoes in Chabahar and Khash Ports in
      Southern Iran" by the first author of this article, year 2011, Islamic Azad
      University, Iran (reference number (Parsia, 2011) [1] of this article). This
      article shows microbial biodiversity and evaluates bio-emulsifier and bio
      demulsifier abilities of capnophile isolates, in order to introduce a superior
      isolate for the Microbial Enhanced Oil Recovery (MEOR) process in the
      petrochemical industry.

PMID- 29034290
TI  - Data on the specificity of an antibody to Drosophila vesicular acetylcholine
      transporter.
AB  - The role of the vesicular acetylcholine transporter (VAChT) in the regulation of
      cholinergic neurotransmission has not been fully elucidated. Here we sought to
      develop a tool for studying vesicular acetylcholine transporter function, and we
      present data on the validation of our new anti-VAChT antibody. We show that the
      immunoreactivity of the antibody is not due to an artifact of secondary antibody
      staining, and we present two additional validation data. First, the peptide
      epitope used to generate the antibody is able to block the binding of the anti
      VAChT antibody in vivo. Further, RNA interference (RNAi) -mediated knockdown of
      VAChT function in cholinergic neurons drastically reduces anti-VAChT staining in
      those constructs. Additional evidence for the antibody functionality is presented
      in our research article on the subject (Boppana et al., 2017) [1].

PMID- 29034292
TI  - Salivary lipocalin family proteins from Panstrongylus chinai, a vector of Chagas
      disease.
AB  - The dataset in this report is related to the research article with the title:
      "Salivary gland transcripts of the kissing bug, Panstrongylus chinai, a vector of
      Chagas disease" (Kato et al., 2017) [1]. Lipocalin family proteins were
      identified as the dominant component in P. chinai saliva, and phylogenetic
      analysis of the salivary lipocalins resulted in the formation of five major
      clades. For further characterization, each clade of P. chinai lipocalin was s
      alignment and phylogenetic analyses together with homologous triatomine
      lipocalins; pallidipin 2, an inhibitor of collagen-induced platelet aggregation
      identified from saliva of Triatoma pallidipennis (clade I), pallidipin-like
      salivary lipocalin from Triatoma dimidiata (clade II), salivary lipocalin from T.
      dimidiata (clade III), triatin-like salivary lipocalin identified in the saliva
      of T. dimidiata (clade IV), and lipocalin-like TiLipo37 from Triatoma infestans
      (clade V).

PMID- 29034293
TI  - Comprehensive data on a 2D-QSAR model for Heme Oxygenase isoform 1 inhibitors.
AB  - The data have been obtained from the Heme Oxygenase Database (HemeOxDB) and
      refined according to the 2D-QSAR requirements. These data provide information
      about a set of more than 380 Heme Oxygenase-1 (HO-1) inhibitors. The development
      of the 2D-QSAR model has been undertaken with the use of CORAL software using
      SMILES, molecular graphs and hybrid descriptors (SMILES and graph together). The
      2D-QSAR model regressions for HO-1 half maximal inhibitory concentration (IC50)
      expressed as pIC50 (pIC50=-LogIC50) are here included. The 2D-QSAR model was also
      employed to predict the HO-1 pIC50values of the FDA approved drugs that are
      herewith reported.

PMID- 29034294
TI  - Dataset on preparation of the phosphorylated counterparts of a Momordica
      charantia protein for studying antifungal activities against susceptible dose
      dependent C. albicans to antimycotics.
AB  - The data presented here are related to a research article entitled "Development
      of a phosphorylated Momordica charantia protein system for inhibiting susceptible
      dose-dependent C. albicans to available antimycotics: An allosteric regulation of
      protein" (Qiao et al., 2017) [1]. The data set includes three portions: (1) a
      relationship between reaction velocities of protein phosphorylation as a function
      of the substrate concentrations, determined in enzymatic reactions in aid of
      protein kinases; (2) a result of antifungal susceptibility testing of C. albicans
      after it is selected in antimycotics; and (3) a comparison of protein expression
      in the susceptible dose-dependent fungus relative to the wild C. albicans. In the
      first portion, the relationship of reaction velocities and substrate
      concentrations is expressed as an output from the inverse variation model. All
      data and analyses are made publicly available and citied in the research article
      using a style for the Data in Brief.

PMID- 29034297
TI  - Microcystic adnexal carcinoma mimicking basal cell carcinoma.

PMID- 29034296
TI  - Diagnosis of asthma in symptomatic children based on measures of lung function:
      an analysis of data from a population-based birth cohort study.
AB  - BACKGROUND: Concerns have been expressed about asthma overdiagnosis. The UK
      National Institute of Health and Care Excellence (NICE) proposed a new diagnostic
      algorithm applying four lung function measures sequentially (ratio of forced
      expiratory volume in 1 s [FEV1] to forced vital capacity [FVC] <70%,
      bronchodilator reversibility >=12%, fractional exhaled nitric oxide [FeNO] >=35
      parts per billion, and peak expiratory flow variability >20%). We aimed to assess
      the diagnostic value of three of the tests individually, and then test the
      proposed algorithm in symptomatic children. METHODS: We used follow-up data at
      age 13-16 years from the Manchester Asthma and Allergy Study, a prospective,
      population-based, birth cohort study. We initially present results for the whole
      population, then by subgroup of disease. To simulate the situation in primary
      care, we included participants reporting symptoms of wheeze, cough, or
      breathlessness in the previous 12 months and who were not on regular inhaled
      corticosteroids. We used an epidemiological definition of current asthma, defined
      as all three of physician-diagnosed asthma, current wheeze, and current use of
      asthma treatment, reported by parents in a validated questionnaire. We assigned
      children with negative answers to all three questions as non-asthmatic controls.
      We also measured spirometry, bronchodilator reversibility, and FeNO at follow-up;
      data for peak expiratory flow variability were not available. We calculated the
      proportion of participants with a current positive lung function test at each
      step of the algorithm, and recorded the number of participants that met our
      definition of asthma. FINDINGS: Of 1184 children born into the cohort, 772
      attended follow-up at age 13-16 years between July 22, 2011, and Nov 11, 2014.
      Among 630 children who completed spirometry, FEV1:FVC was less than 70% in ten
      (2%) children, of whom only two (20%) had current asthma. Bronchodilator
      reversibility was positive in 54 (9%) of 624 children, of whom only 12 (22%) had
      current asthma. FeNO was 35 or more parts per billion in 115 (24%) of 485
      children, of whom 29 (25%) had current asthma. Only four of 56 children with
      current asthma had positive results for all three tests (spirometry,
      bronchodilator reversibility, and FeNO). Conversely, 24 (43%) of the 56 children
      with current asthma were negative on all three tests. FEV1:fvc (p=0.0075) and
      FeNO (p<0.0001), but not bronchodilator reversibility (p=0.97), were
      independently associated with asthma in multivariable logistic regression models.
      Among children who reported recent symptoms, the diagnostic accuracy of the
      algorithm was poor. INTERPRETATION: Our findings challenge the proposed cutoff
      values for spirometry, the order in which the lung function tests are done, and
      the position of bronchodilator reversibility within the algorithm sequence. Until
      better evidence is available, the proposed NICE algorithm on asthma diagnosis
      should not be implemented in children. FUNDING: UK Medical Research Council.

PMID- 29034295
TI  - Data demonstrating the role of peroxiredoxin 2 as important anti-oxidant system
      in lung homeostasis.
AB  - The data presented in this article are related to the research paper entitled
      "peroxiredoxin-2 plays a pivotal role as multimodal cytoprotector in the early
      phase of pulmonary hypertension" (Federti et al., 2017) [1]. Data show that the
      absence of peroxiredoxin-2 (Prx2) is associated with increased lung oxidation and
      pulmonary vascular endothelial dysfunction. Prx2-/- mice displayed activation of
      the redox-sensitive transcriptional factors, NF-kB and Nrf2, and increased
      expression of cytoprotective system such as heme-oxygenase-1 (HO-1). We also
      noted increased expression of both markers of vascular activation and
      extracellular matrix remodeling. The administration of the recombinant fusion
      protein PEP Prx2 reduced the activation of NF-kB and Nrf2 and was paralleled by a
      decrease in HO-1 and in vascular endothelial abnormal activation. Prolonged
      hypoxia was used to trigger pulmonary artery hypertension (PAH). Prx2-/-
      precociously developed PAH compared to wildtype animals.

PMID- 29034298
TI  - Generalized pustular psoriasis treated with apremilast in a patient with multiple
      medical comorbidities.

PMID- 29034299
TI  - A case of Merkel cell carcinoma development under treatment with a Janus kinase
      inhibitor.

PMID- 29034300
TI  - Generating method-specific Reference Ranges - A harmonious outcome?
AB  - OBJECTIVES: When laboratory Reference Ranges (RR) do not reflect analytical
      methodology, result interpretation can cause misclassification of patients and
      inappropriate management. This can be mitigated by determining and implementing
      method-specific RRs, which was the main objective of this study. DESIGN AND
      METHODS: Serum was obtained from healthy volunteers (Male + Female, n > 120)
      attending hospital health-check sessions during June and July 2011. Pseudo
      anonymised aliquots were stored (at - 70  degrees C) prior t degrees  analysis on
      Abbott ARCHITECT c16000 chemistry and i2000SR immunoassay analysers. Data were
      stratified by gender where appropriate. Outliers were excluded statistically
      (Tukey method) to generate non-parametric RRs (2.5th + 97.5th percentiles). RRs
      were compared to those quoted by Abbott and UK Pathology Harmony (PH) where
      possible. For 7 selected tests, RRs were verified using a data mining approach.
      RESULTS: For chemistry tests (n = 23), Upper or Lower Reference Limits (LRL or
      URL) were > 20% different from Abbott ranges in 25% of tests (11% from PH ranges)
      but in 38% for immunoassay tests (n = 13). RRs (mmol/L) for sodium (138-144),
      potassium (3.8-4.9) and chloride (102-110) were considerably narrower than PH
      ranges (133-146, 3.5-5.0 and 95-108, respectively). The gender difference for
      ferritin (M: 29-441, F: 8-193 ng/mL) was more pronounced than reported by Abbott
      (M: 22-275, F: 5-204 ng/mL). Verification studies showed good agreement for
      chemistry tests (mean [SD] difference = 0.4% [1.2%]) but less so for immunoassay
      tests (27% [29%]), particularly for TSH (LRL). CONCLUSION: Where resource
      permits, we advocate using method-specific RRs in preference to other sources,
      particularly where method bias and lack of standardisation limits RR
      transferability and harmonisation.

PMID- 29034301
TI  - Effects of one directional pneumatic tube system on routine hematology and
      chemistry parameters; A validation study at a tertiary care hospital.
AB  - BACKGROUND: The validation of sample stability through pneumatic tube system
      (PTS) is essential. The objective of this study was to evaluate the effects of
      PTS transportation on laboratory results. METHODS: Paired EDTA and SST blood
      samples were collected from 56 randomly selected patients. Laboratory parameters
      were compared between PTS group and hand-delivered group. RESULTS: No statistical
      differences were observed for complete blood counts, white blood cell
      differential parameters, erythrocyte sedimentation rate and most chemistry
      parameters between PTS and hand-delivered transport procedures. Mean platelet
      volume results obtained from samples transported through PTS were lower than that
      obtained from samples transported through hand-delivered method (P = 0.001). The
      results of aspartate aminotransferase (P = 0.000), lactate dehydrogenase (P =
      0.000), and hemolysis index (P = 0.000) from PTS group were higher than that from
      hand-delivered group. CONCLUSIONS: All laboratories should validate the stability
      of the results from samples according to transportation method.

PMID- 29034302
TI  - Comparison of two immunoassay systems for hCGbeta and PAPP-A in prenatal
      screening for trisomy 21, 18, and 13 in the first trimester.
AB  - OBJECTIVES: The biochemical serum markers free beta-human chorionic gonadotropin
      (hCGbeta) and pregnancy associated plasma protein A (PAPP-A), used in screening
      for trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13) during the first
      trimester, can be measured on different laboratory instruments e.g. Kryptor
      (Brahms) and Cobas (Roche). We compared the performance of these two analytical
      instruments when used for first trimester combined testing. DESIGN AND METHODS:
      Serum samples from 944 singleton pregnant women attending for first trimester
      combined testing were routinely assayed for hCGbeta and PAPP-A on Kryptor, and re
      analyzed on Cobas. In addition, serum samples from 70 pregnant women carrying a
      fetus affected by T21, T18 or T13, were re-assayed on Cobas. RESULTS: For the
      screening population, the hCGbeta and PAPP-A results in multiples of the median
      (MoM) from Kryptor and Cobas were significantly lower on Cobas when compared to
      Kryptor. The number of pregnant women with a risk above 1:300 for T21 was 48 for
      both Cobas and Kryptor, although a few patients only had a high risk with one of
      the methods. Overall, the screen positive rate was 5.1% for both instruments. In
      the trisomy groups the calculated risks for T21, T18, and T13 agreed well between
      Cobas and Kryptor. CONCLUSIONS: The screen positive rate for T21 (5.1%) did not
      differ between the two analytical platforms in our screening population, although
      PAPP-A measurements form Cobas were significantly lower than those from Kryptor.
      The calculated risks for the pregnancies affected by trisomies using hCGbeta MoM
      and PAPP-A MoM from Kryptor agreed well with those from Cobas.

PMID- 29034303
TI  - Validation of capillary blood analysis and capillary testing mode on the epoc
      Point of Care system.
AB  - BACKGROUND: Laboratory test in transport is a critical component of patient care,
      and capillary blood is a preferred sample type particularly in children. This
      study evaluated the performance of capillary blood testing on the epoc Point of
      Care Blood Analysis System (Alere Inc). METHODS: Ten fresh venous blood samples
      was tested on the epoc system under the capillary mode. Correlation with GEM 4000
      (Instrumentation Laboratory) was examined for Na+, K+, Cl-, Ca2+, glucose,
      lactate, hematocrit, hemoglobin, pO2, pCO2, and pH, and correlation with serum
      tested on Vitros 5600 (Ortho Clinical Diagnostics) was examined for creatinine.
      Eight paired capillary and venous blood was tested on epoc and ABL800
      (Radiometer) for the correlation of Na+, K+, Cl-, Ca2+, glucose, lactate,
      hematocrit, hemoglobin, pCO2, and pH. Capillary blood from 23 apparently healthy
      volunteers was tested on the epoc system to assess the concordance to reference
      ranges used locally. RESULTS: Deming regression correlation coefficients for all
      the comparisons were above 0.65 except for ionized Ca2+. Accordance of greater
      than 85% to the local reference ranges were found in all assays with the
      exception of pO2 and Cl-. CONCLUSION: Data from this study indicates that
      capillary blood tests on the epoc system provide comparable results to reference
      method for these assays, Na+, K+, glucose, lactate, hematocrit, hemoglobin, pCO2,
      and pH. Further validation in critically ill patients is needed to implement the
      epoc system in patient transport. IMPACT OF THE STUDY: This study demonstrated
      that capillary blood tests on the epoc Point of Care Blood Analysis System give
      comparable results to other chemistry analyzers for major blood gas and critical
      tests. The results are informative to institutions where pre-hospital and inter
      hospital laboratory testing on capillary blood is a critical component of patient
      point of care testing.

PMID- 29034304
TI  - Validated low-volume aldosterone immunoassay tailored to GCLP-compliant
      investigations in small sample volumes.
AB  - INTRODUCTION: Heart failure is well investigated in adults, but data in children
      is lacking. To overcome this shortage of reliable data, appropriate bioanalytical
      assays are required. OBJECTIVES: Development and validation of a bioanalytical
      assay for the determination of aldosterone concentrations in small sample volumes
      applicable to clinical studies under Good Clinical Laboratory Practice. METHODS:
      An immunoassay was developed based on a commercially available enzyme-linked
      immunosorbent assay and validated according to current bioanalytical guidelines
      of the EMA and FDA. RESULTS: The assay (range 31.3-1000 pg/mL [86.9-2775 pmol/L])
      is characterized by a between-run accuracy from - 3.8% to - 0.8% and a between
      run imprecision ranging from 4.9% to 8.9% (coefficient of variation). For within
      run accuracy, the relative error was between - 11.1% and + 9.0%, while within-run
      imprecision ranged from 1.2% to 11.8% (CV). For parallelism and dilutional
      linearity, the relative error of back-calculated concentrations varied from -
      14.1% to + 8.4% and from - 7.4% to + 10.5%, respectively. CONCLUSIONS: The
      immunoassay is compliant with the bioanalytical guidelines of the EMA and FDA and
      allows accurate and precise aldosterone determinations. As the assay can run low
      volume samples, it is especially valuable for pediatric investigations.

PMID- 29034305
TI  - Fecal zonulin is elevated in Crohn's disease and in cigarette smokers.
AB  - OBJECTIVES: Human zonulin is a protein that increases permeability in the
      epithelial layer of the small intestine by reversibly modulating the
      intercellular tight junctions. There is not sufficient information available
      about zonulin's participation in inflammatory bowel diseases (IBD). The aim of
      this study was therefore to investigate fecal and serum zonulin in IBD patients
      and its relation to the disease localization, behavior and smoking status. DESIGN
      AND METHODS: Forty IBD patients and forty healthy persons were examined for fecal
      and serum zonulin concentrations by competitive ELISA (DRG International Inc).
      Values were correlated to IBD type, localization and behavior, and smoking.
      RESULTS: Serum and fecal zonulin were significantly higher in patients with
      Crohn's disease compared to ulcerative colitis (p = 0.038 for fecal zonulin, and
      p = 0.041 for serum zonulin concentrations). No association of serum or fecal
      zonulin was found with respect to IBD localization and behavior. The only
      difference was found with respect to smoking. Both the IBD cohort and healthy
      smokers showed significantly higher fecal zonulin levels (median 203 ng/mL)
      compared to non-smokers (median 35.8 ng/mL), p < 0.001. CONCLUSIONS: Fecal and
      serum zonulin levels are elevated in patients with active Crohn's disease but not
      with ulcerative colitis. High fecal zonulin levels in smokers irrespective of IBD
      point to the significant and undesirable up-regulation of gut permeability in
      cigarette smokers.

PMID- 29034306
TI  - Prolonged survival after intraperitoneal interleukin-2 immunotherapy for
      recurrent ovarian cancer.
AB  - *A case report of a 14 year remission of recurrent ovarian cancer with
      intraperitoneal aldesleukin (IL-2) is presented.*Intraperitoneal IL-2 was given
      with little toxicity.*Immunotherapy may have the potential for durable remissions
      in ovarian cancer.

PMID- 29034307
TI  - Uterine Clostridium perfringens infection related to gynecologic malignancy.
AB  - Uterine gas gangrene caused by Clostridium perfringens is a serious, often life
      threatening infection that is rarely encountered in the practice of gynecologic
      oncology. However, the hypoxic nature of gynecologic cancers due to necrosis
      and/or prior radiation therapy creates a microenvironment optimal for
      proliferation of anaerobic bacteria such as the Clostridium species. Early
      recognition and aggressive treatment with IV antibiotics and surgical debridement
      remain the cornerstones of management in order to decrease morbidity and
      mortality. Here we present the case of a 52 year-old woman with a remote history
      of cervical cancer who was previously treated at our institution with primary
      chemotherapy and radiation and was then admitted decades later with Clostridium
      perfringens bacteremia and CT evidence of intrauterine abscess. The patient
      received a prolonged course of IV antibiotic therapy and subsequently underwent
      definitive surgical management with a total abdominal hysterectomy, bilateral
      salpingo-oophorectomy, small bowel resection with anastomosis for a utero-ileal
      fistula identified intraoperatively. Pathology from the uterine specimen
      demonstrated a primary poorly differentiated uterine adenocarcinoma. The patient
      recovered fully from her Clostridium perfringens infection and was discharged
      from the hospital shortly after surgical intervention.

PMID- 29034308
TI  - Cost-effectiveness analysis study of HPV testing as a primary cervical cancer
      screening in Thailand.
AB  - OBJECTIVES: The aim of this study is to compare the cost and benefit of four
      different cervical cancer screening strategies involving primary HPV 16/18
      genotyping, hrHPV testing alone and cytology for detecting CIN2 +. METHODS:
      Economical analysis using Markov modeling approach to combine the epidemiological
      data from current population-based study of The National Cancer Institute of
      Thailand. A cohort of 100,000 hypothetical female population age 30-65 years was
      simulated in each strategy. The compared strategies are HPV 16/18 genotyping with
      reflexed cytology, hrHPV testing alone followed by colposcopy, Papanicolaou
      standard cytology and liquid based cytology followed by colposcopy. The interval
      of screening was 5 years' interval. The main outcomes were defined as a number of
      CIN2 + cases and cost per 100,000 women screening over 35 years. RESULTS: Model
      predictions indicated that, the most cost-effectiveness strategy is hrHPV testing
      alone by reducing cost and also increase CIN2 + detection rate. It identify an
      additional 130 cases and decrease cost by 46,950,840 THB (1,394,441 USD) per
      100,000 women screened when compared to HPV 16/18 genotyping. Compared with
      cytology, hrHPV testing decrease cost by 51,279,781 THB (1,523,011 USD) and
      detected more 506 cases of CIN2 +. From sensitivity analysis, the cost of HPV
      testing, cost of colposcopy, incidence of HPV infection and sensitivity of
      cytology may affect the results. (1 USD = 33.67 Baht). CONCLUSION: The results of
      this cost-effectiveness analysis support the full scale implementation of HPV
      testing as a primary cervical cancer screening in Thailand.

PMID- 29034309
TI  - Metastatic uterine tumor resembling ovarian sex cord tumor: A case report and
      review of the literature.
AB  - Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are rare and
      commonly characterized as benign tumors, with infrequent reports of metastasis
      and recurrence. Treatment recommendations have not been well established,
      particularly for more advanced cases. We present the first reported death from a
      metastatic UTROSCT, summarize the available literature, and describe
      characteristics common to UTROSCTs with aggressive features. In this case, a 49
      year-old woman presented with abdominal distension and pain; initial imaging and
      diagnostic workup suggested metastatic epithelial ovarian cancer to be the cause.
      The patient subsequently underwent neoadjuvant chemotherapy followed by optimal
      cytoreductive surgery and adjuvant chemotherapy. Final pathology revealed UTROSCT
      with omental and peritoneal metastases. She then underwent adjuvant chemotherapy
      with subsequent recurrence and died 15 months after her initial diagnosis. Our
      analysis of this case and the available literature led us to identify pathologic
      risk factors that may help predict aggressive UTROSCT behavior.

PMID- 29034310
TI  - Further education improves cognitive reserve and triggers improvement in
      selective cognitive functions in older adults: The Tasmanian Healthy Brain
      Project.
AB  - INTRODUCTION: The strong link between early-life education and subsequent reduced
      risk of dementia suggests that education in later life could enhance cognitive
      function and may reduce age-related cognitive decline and protect against
      dementia. METHODS: Episodic memory, working memory, executive function, and
      language processing performances were assessed annually over 4 years in 359
      healthy older adults who attended university for a minimum of 12 months
      (intervention) and were compared against 100 healthy adult controls. RESULTS:
      Multiple group latent growth curve modeling revealed a significant improvement in
      language processing capacity over time in the intervention group. No changes were
      detected for episodic memory, working memory, or executive function. DISCUSSION:
      These results suggest that complex mental stimulation resulting from late-life
      further education results in improved crystallized knowledge but no changes to
      fluid cognitive functions.

PMID- 29034311
TI  - Left atrial deformation: Useful index for early detection of cardiac damage in
      chronic mitral regurgitation.
AB  - In chronic mitral regurgitation (MR) left atrium is one of the first cardiac
      structures that is involved in remodeling and ultrastructural changes for a
      progressive volume overload. Severe left atrial (LA) dilation on echocardiography
      and new onset of atrial fibrillation in asymptomatic patients with preserved Left
      Ventricular (LV) function, appeared as a Class IIb recommendation for
      consideration for surgical mitral valve repair in the actual guidelines. However,
      before atrial dilatation and dysfunction, several ultrastructural changes appear
      in the atrial muscle tissue that are difficult to identify with the standard
      echocardiography. Speckle tracking echocardiography (STE) can analyze LA
      function: it has been showed that it can indirectly identify structural tissue
      modifications from excessive atrial effort in the early stages of MR up to the
      full depression of atrial function in the late stages where there are advanced
      ultrastructural alterations. This review aims to summarize current knowledge on
      the role of atrial strain identifying early structural alterations of the atrial
      tissue in the rising stages of MR considering that Left Atrial Peak Longitudinal
      Strain (PALS) considered useful parameter for a more extensive evaluation of MR
      patients.

PMID- 29034312
TI  - TGF-beta Inhibition Improves Oncolytic Herpes Viroimmunotherapy in Murine Models
      of Rhabdomyosarcoma.
AB  - Oncolytic viruses are an emerging class of cancer therapeutics that couple
      cytotoxicity with the induction of an anti-tumor immune response. Host-virus
      interactions are complex and modulated by a tumor microenvironment whose
      immunosuppressive activities can limit the effectiveness of cancer
      immunotherapies. In an effort to improve this aspect of oncolytic virotherapy, we
      combined the oncolytic herpes virus HSV1716 with the transforming growth factor
      beta receptor 1 (TGF-betaR1) inhibitor A8301 to treat syngeneic models of murine
      rhabdomyosarcoma. Mice that received HSV1716 or A8301 alone showed little to no
      benefit in efficacy and survival over controls. Conversely, mice given
      combination therapy exhibited tumor stabilization throughout the treatment
      regimen, which was reflected in significantly prolonged survival times including
      some complete responses. In vitro cell viability and virus replication assays
      showed that the rhabdomyosarcoma cell lines were generally insensitive to HSV1716
      and A8301. Likewise, in vivo virus replication assays showed that HSV1716 titers
      moderately decreased in the presence of A8301. The enhanced efficacy instead
      appears to be dependent on the generation of an improved anti-tumor T cell
      response as determined by its loss in athymic nude mice and following in vivo
      depletion of either CD4+ or CD8+ cells. These data suggest TGF-beta inhibition
      can augment the immunotherapeutic efficacy of oncolytic herpes virotherapy.

PMID- 29034313
TI  - Newly Characterized Murine Undifferentiated Sarcoma Models Sensitive to
      Virotherapy with Oncolytic HSV-1 M002.
AB  - Despite advances in conventional chemotherapy, surgical techniques, and
      radiation, outcomes for patients with relapsed, refractory, or metastatic soft
      tissue sarcomas are dismal. Survivors often suffer from lasting morbidity from
      current treatments. New targeted therapies with less toxicity, such as those that
      harness the immune system, and immunocompetent murine sarcoma models to test
      these therapies are greatly needed. We characterized two new serendipitous murine
      models of undifferentiated sarcoma (SARC-28 and SARC-45) and tested their
      sensitivity to virotherapy with oncolytic herpes simplex virus 1 (HSV-1). Both
      models expressed high levels of the primary HSV entry molecule nectin-1 (CD111)
      and were susceptible to killing by interleukin-12 (IL-12) producing HSV-1 M002 in
      vitro and in vivo. M002 resulted in a significant intratumoral increase in
      effector CD4+ and CD8+ T cells and activated monocytes, and a decrease in myeloid
      derived suppressor cells (MDSCs) in immunocompetent mice. Compared to parent
      virus R3659 (no IL-12 production), M002 resulted in higher CD8:MDSC and CD8:T
      regulatory cell (Treg) ratios, suggesting that M002 creates a more favorable
      immune tumor microenvironment. These data provide support for clinical trials
      targeting sarcomas with oncolytic HSV-1. These models provide an exciting
      opportunity to explore combination therapies for soft tissue sarcomas that rely
      on an intact immune system to reach full therapeutic potential.

PMID- 29034314
TI  - Targeting an Oncolytic Influenza A Virus to Tumor Tissue by Elastase.
AB  - Oncolytic viruses are currently established as a novel type of immunotherapy. The
      challenge is to safely target oncolytic viruses to tumors. Previously, we have
      generated influenza A viruses (IAVs) containing deletions in the viral interferon
      antagonist. Those deletions have attenuated the virus in normal tissue but
      allowed replication in tumor cells. IAV entry is mediated by hemagglutinin (HA),
      which needs to be activated by a serine protease, for example, through trypsin.
      To further target the IAV to tumors, we have changed the trypsin cleavage site to
      an elastase cleavage site. We chose this cleavage site because elastase is
      expressed in the tumor microenvironment. Moreover, the exchange of the cleavage
      site previously has been shown to attenuate viral growth in lungs. Newly
      generated elastase-activated influenza viruses (AE viruses) grew to similar
      titers in tumor cells as the trypsin-activated counterparts (AT viruses).
      Intratumoral injection of AE viruses into syngeneic B16f1 melanoma-derived tumors
      in mice reduced tumor growth similar to AT viruses and had a better therapeutic
      effect in heterologous human PANC-1-derived tumors. Therefore, the introduction
      of the attenuation marker "elastase cleavage site" in viral HA allows for safe,
      effective oncolytic virus therapy.

PMID- 29034315
TI  - Emergence of beta-Band Oscillations in the Aged Rat Amygdala during
      Discrimination Learning and Decision Making Tasks.
AB  - Older adults tend to use strategies that differ from those used by young adults
      to solve decision-making tasks. MRI experiments suggest that altered strategy use
      during aging can be accompanied by a change in extent of activation of a given
      brain region, inter-hemispheric bilateralization or added brain structures. It
      has been suggested that these changes reflect compensation for less effective
      networks to enable optimal performance. One way that communication can be
      influenced within and between brain networks is through oscillatory events that
      help structure and synchronize incoming and outgoing information. It is unknown
      how aging impacts local oscillatory activity within the basolateral complex of
      the amygdala (BLA). The present study recorded local field potentials (LFPs) and
      single units in old and young rats during the performance of tasks that involve
      discrimination learning and probabilistic decision making. We found task- and age
      specific increases in power selectively within the beta range (15-30 Hz). The
      increased beta power occurred after lever presses, as old animals reached the
      goal location. Periods of high-power beta developed over training days in the
      aged rats, and was greatest in early trials of a session. beta Power was also
      greater after pressing for the large reward option. These data suggest that aging
      of BLA networks results in strengthened synchrony of beta oscillations when older
      animals are learning or deciding between rewards of different size. Whether this
      increased synchrony reflects the neural basis of a compensatory strategy change
      of old animals in reward-based decision-making tasks, remains to be verified.

PMID- 29034317
TI  - Luciferase shRNA Presents off-Target Effects on Voltage-Gated Ion Channels in
      Mouse Hippocampal Pyramidal Neurons.
AB  - RNA interference (RNAi) is a straightforward approach to study gene function from
      the in vitro cellular level to in vivo animal behavior. Although RNAi-mediated
      gene knockdown has become essentially routine in neuroscience over the past ten
      years, off-target effects of short hairpin RNAs (shRNAs) should be considered as
      the proper choice of control shRNA is critical in order to perform meaningful
      experiments. Luciferase shRNA (shLuc), targeting firefly luciferase, and
      scrambled shRNAs (shScrs) have been widely used as controls for vertebrate cell
      research. However, thorough validation of control shRNAs has not been made to
      date. Here, we performed thorough physiological and morphological studies against
      control shRNAs in mouse hippocampal CA1 pyramidal neurons. As expected, all
      control shRNAs exhibited normal basal synaptic transmission and dendritic
      morphology. However, to our surprise, shLuc exerted severe off-target effects on
      voltage-gated ion channel function, while the shScr had no detectable changes.
      These results indicate that thorough validation of shRNA is imperative and, in
      the absence of such validation, that shScr is the best available negative control
      for gene knockdown studies.

PMID- 29034316
TI  - Large-Scale Network Coupling with the Fusiform Cortex Facilitates Future Social
      Motivation.
AB  - Large-scale functional networks, as identified through the coordinated activity
      of spatially distributed brain regions, have become central objects of study in
      neuroscience because of their contributions to many processing domains. Yet, it
      remains unclear how these domain-general networks interact with focal brain
      regions to coordinate thought and action. Here, we investigated how the default
      mode network (DMN) and executive control network (ECN), two networks associated
      with goal-directed behavior, shape task performance through their coupling with
      other cortical regions several seconds in advance of behavior. We measured these
      networks' connectivity during an adaptation of the monetary incentive delay (MID)
      response-time task in which human participants viewed social and nonsocial images
      (i.e., pictures of faces and landscapes, respectively) while brain activity was
      measured using fMRI. We found that participants displayed slower reaction times
      (RTs) subsequent to social trials relative to nonsocial trials. To examine the
      neural mechanisms driving this subsequent-RT effect, we integrated independent
      components analysis (ICA) and a network-based psychophysiological interaction
      (nPPI) analysis; this allowed us to investigate task-related changes in network
      coupling that preceded the observed trial-to-trial variation in RT. Strikingly,
      when subjects viewed social rewards, an area of the fusiform gyrus (FG)
      consistent with the functionally-defined fusiform face area (FFA) exhibited
      increased coupling with the ECN (relative to the DMN), and the relative magnitude
      of coupling tracked the slowing of RT on the following trial. These results
      demonstrate how large-scale, domain-general networks can interact with focal,
      domain-specific cortical regions to orchestrate subsequent behavior.

PMID- 29034318
TI  - Mediodorsal Thalamic Neurons Mirror the Activity of Medial Prefrontal Neurons
      Responding to Movement and Reinforcement during a Dynamic DNMTP Task.
AB  - The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to
      support learning and adaptive decision-making. MD receives driver (layer 5) and
      modulatory (layer 6) projections from PFC and is the main source of driver
      thalamic projections to middle cortical layers of PFC. Little is known about the
      activity of MD neurons and their influence on PFC during decision-making. We
      recorded MD neurons in rats performing a dynamic delayed nonmatching to position
      (dDNMTP) task and compared results to a previous study of mPFC with the same task
      (Onos et al., 2016). Criterion event-related responses were observed for 22%
      (254/1179) of neurons recorded in MD, 237 (93%) of which exhibited activity
      consistent with mPFC response types. More MD than mPFC neurons exhibited
      responses related to movement (45% vs. 29%) and reinforcement (51% vs. 27%). MD
      had few responses related to lever presses, and none related to preparation or
      memory delay, which constituted 43% of event-related activity in mPFC. Comparison
      of averaged normalized population activity and population response times
      confirmed the broad similarity of common response types in MD and mPFC and
      revealed differences in the onset and offset of some response types. Our results
      show that MD represents information about actions and outcomes essential for
      decision-making during dDNMTP, consistent with evidence from lesion studies that
      MD supports reward-based learning and action-selection. These findings support
      the hypothesis that MD reinforces task-relevant neural activity in PFC that gives
      rise to adaptive behavior.

PMID- 29034319
TI  - High-Precision Fast-Spiking Basket Cell Discharges during Complex Events in the
      Human Neocortex.
AB  - In the human neocortex, solitary action potentials in some layer 2-3 pyramidal
      cells (PCs) trigger brief episodes of network activity known as complex events
      through strong excitatory synapses that specifically innervate GABAergic
      interneurons. Yet, how these "master PCs" configure the local network activity is
      not well understood. We report that single spikes in the PCs, studied here in
      synaptically connected cell pairs in frontal or temporal neocortical areas of
      both males and females, elicit firing of fast-spiking basket cells (FSBCs) with a
      short delay (on average 2.7 ms). The FSBC discharge is triggered by 13 mV (on
      average) monosynaptic EPSPs, and the action potential is time locked to the
      master PC spike with high temporal precision, showing little jitter in delay. In
      the complex events, the FSBC discharge occurs in the beginning of the activity
      episode, forming the first wave of the complex event activity. Firing of FSBCs
      generates GABAergic IPSCs with fast kinetics in layer 2-3 PCs, and similar IPSCs
      regularly occur time locked to master PC spikes in the beginning of the complex
      events with high probability and short (median 4.1 ms) delay with little jitter.
      In comparison, discharge of nonfast spiking interneurons (non-FSINs) investigated
      here appears inconsistently in the complex events and shows low probability.
      Thus, firing of layer 2-3 FSBCs with high temporal fidelity characterizes early
      phase of the complex events in the human neocortex.

PMID- 29034320
TI  - Fetal brain extracellular matrix boosts neuronal network formation in 3D
      bioengineered model of cortical brain tissue.
AB  - The extracellular matrix (ECM) constituting up to 20% of the organ volume is a
      significant component of the brain due to its instructive role in the
      compartmentalization of functional microdomains in every brain structure. The
      composition, quantity and structure of ECM changes dramatically during the
      development of an organism greatly contributing to the remarkably sophisticated
      architecture and function of the brain. Since fetal brain is highly plastic, we
      hypothesize that the fetal brain ECM may contain cues promoting neural growth and
      differentiation, highly desired in regenerative medicine. Thus, we studied the
      effect of brain-derived fetal and adult ECM complemented with matricellular
      proteins on cortical neurons using in vitro 3D bioengineered model of cortical
      brain tissue. The tested parameters included neuronal network density, cell
      viability, calcium signaling and electrophysiology. Both, adult and fetal brain
      ECM as well as matricellular proteins significantly improved neural network
      formation as compared to single component, collagen I matrix. Additionally, the
      brain ECM improved cell viability and lowered glutamate release. The fetal brain
      ECM induced superior neural network formation, calcium signaling and spontaneous
      spiking activity over adult brain ECM. This study highlights the difference in
      the neuroinductive properties of fetal and adult brain ECM and suggests that
      delineating the basis for this divergence may have implications for regenerative
      medicine.

PMID- 29034321
TI  - Refractory versus resistant hypertension: Novel distinctive phenotypes.
AB  - Resistant hypertension (RHTN) is relatively common with an estimated prevalence
      of 10-20% of treated hypertensive patients. It is defined as blood pressure (BP)
      >140/90 mmHg treated with >=3 antihypertensive medications, including a diuretic,
      if tolerated. Refractory hypertension is a novel phenotype of severe
      antihypertensive treatment failure. The proposed definition for refractory
      hypertension, i.e. BP >140/90 mmHg with use of >=5 different antihypertensive
      medications, including a diuretic and a mineralocorticoid receptor antagonist
      (MRA) has been applied inconsistently. In comparison to RHTN, refractory
      hypertension seems to be less prevalent than RHTN. This review focuses on current
      knowledge about this novel phenotype compared with RHTN including definition,
      prevalence, mechanisms, characteristics and comorbidities, including
      cardiovascular risk. In patients with RHTN excess fluid retention is thought to
      be a common mechanism for the development of RHTN. Recently, evidence has emerged
      suggesting that refractory hypertension may be more of neurogenic etiology due to
      increased sympathetic activity as opposed to excess fluid retention. Treatment
      recommendations for RHTN are generally based on use and intensification of
      diuretic therapy, especially with the combination of a long-acting thiazide-like
      diuretic and an MRA. Based on findings from available studies, such an approach
      does not seem to be a successful strategy to control BP in patients with
      refractory hypertension and effective sympathetic inhibition in such patients,
      either with medications and/or device based approaches may be needed.

PMID- 29034322
TI  - Socioeconomic Segregation of Activity Spaces in Urban Neighborhoods: Does Shared
      Residence Mean Shared Routines?
AB  - Residential segregation by income and education is increasing alongside slowly
      declining black-white segregation. Segregation in urban neighborhood residents'
      non-home activity spaces has not been explored. How integrated are the daily
      routines of people who live in the same neighborhood? Are people with different
      socioeconomic backgrounds that live near one another less likely to share routine
      activity locations than those of similar education or income? Do these patterns
      vary across the socioeconomic continuum or by neighborhood structure? The
      analyses draw on unique data from the Los Angeles Family and Neighborhood Survey
      that identify the location where residents engage in routine activities. Using
      multilevel p2 (network) models, we analyze pairs of households located in the
      same neighborhood and examine whether the dyad combinations across three levels
      of SES conduct routine activities in the same location, and whether neighbor
      socioeconomic similarity in the co-location of routine activities is dependent on
      the level of neighborhood socioeconomic inequality and trust. Results indicate
      that, on average, increasing SES diminishes the likelihood of sharing activity
      locations with any SES group. This pattern is most pronounced in neighborhoods
      characterized by high levels of socioeconomic inequality. Neighborhood trust
      explains a nontrivial proportion of the inequality effect on the extent of
      routine activity sorting by SES. Thus stark, visible neighborhood-level
      inequality by SES may lead to enhanced effects of distrust on the willingness to
      share routines across class.

PMID- 29034324
TI  - A Review of Epidemiologic Studies of the Health of Gulf War Women Veterans.
AB  - INTRODUCTION: In the 25 years since the 1990-1991 Gulf War (GW), studies have
      evaluated Gulf War Illness (GWI), sometimes referred to as medically unexplained
      multi symptom illness, and other medical and neurological conditions in women GW
      veterans. MATERIALS AND METHODS: In this article, we review epidemiologic studies
      of the health of women who served in the 1990-1991 GW based upon bibliographic
      searches in PubMed and CINAHL with relevant search terms through September 2015.
      RESULTS: A total of 56 articles were identified in the bibliographic searches. By
      screening abstracts or full-text articles, a total of 21 relevant studies were
      identified. Results from some studies, but not all, suggest that GWI is more
      common in women GW veterans than their male counterparts. Few studies of GW
      veterans focused on women's health. A small number of studies suggested excess
      rates of woman's health problems, e.g., breast cysts, abnormal Papanicolaou (Pap)
      smears, yeast infections, and bladder infections. Several studies have identified
      significantly elevated rates of birth defects and adverse reproductive outcomes
      among GW veterans. However, findings have varied with different study designs and
      sample sizes, with some studies showing elevated risks of stillbirths,
      miscarriages, and/or birth defects and others have not. In some studies,
      participants reported increased risks of ectopic pregnancies and spontaneous
      abortions. CONCLUSION: Further research is needed to provide a comprehensive
      picture of the health of women GW veterans and to examine a broad range of
      women's health issues including adverse reproductive outcomes. Some deployment
      related health problems only become apparent decades later and other conditions
      may worsen or improve over time. Assessments are needed of current health status,
      changes in health symptoms and conditions over time, and possible differences in
      health outcomes associated with specific experiences and exposures during the
      war. Future studies would be strengthened by assessing GWI symptom patterns that
      may be specific to women veterans, examine diagnosed medical conditions among
      women veterans, and evaluate changes in women's health over time, including
      changes potentially associated with menopause and age.

PMID- 29034323
TI  - Hypothesizing that a Pro-Dopaminergic Regulator (KB220zTM Liquid Variant) can
      Induce "Dopamine Homeostasis" and Provide Adjunctive Detoxification Benefits in
      Opiate/Opioid Dependence.
AB  - In order to explore the initiation of detoxification of addictive patients to
      opiates/opioids (along with some other anti-withdrawal agents), we developed a
      protocol to be utilized in treatment centers particularly with heavily dependent
      opiate/opioid subjects. Out of 17 subjects, only three received
      Buprenorphine/Naloxone (Bup/nx) along with KB220Z. In this pilot, we first used a
      dose of KB220Z of 2 oz twice daily before meals along with clonidine and
      benzodiazepines and other anti-nausea and sleep aids including Gabapentin. The
      dose of KB220Z was maintained for 6 days in five individuals. In a second
      scenario, we utilized a higher dose of 4 oz every 6 hours, over a 6-day period.
      The higher dose was employed in another 12 patients. It is noteworthy that only 3
      people have relapsed utilizing these two protocols during the first two weeks of
      the study, allowing for the remaining 82% to be maintained on KB220Z. The
      patients have been maintained without any additional Bup/nx for a minimum of 120
      days and in one subject, 214 days. We are in the process of testing this
      hypothesis in multiple treatment centers across the United Sates utilizing data
      from the Clinical opiate Withdrawal Scale (COWS) pre and post KB220Z. We are in
      the process of testing this hypothesis in multiple treatment centers across the
      United Sates. While this does not constitute an acceptable controlled experiment,
      it does provide some preliminary evidence that agrees with an earlier study.
      Moreover, because of the utilization of standard detoxifying agents in this
      detoxification protocol, we cannot make any inference to KB220Z's effects.
      However, out of 17 subjects, only three required Bup/nx suggesting an interesting
      finding. If further confirmed in larger studies, the utilization for
      opiate/opioid detoxification may provide a novel way to eliminate the need for
      addictive opioids during withdrawal and detoxification. This paradigm shift may
      translate to a reduction in utilizing powerful and addictive opioids like
      buprenorphine and methadone (especially in these patients at high genetic risk
      for addiction) as not only detoxifying agents, but also maintenance drugs. While
      extensive research is required, this pilot paves the way for future
      investigations that could assist in the reduction of addictive opiate/opioid use
      and mortalities amongst both the young and old in America.

PMID- 29034325
TI  - Collection of Viable Aerosolized Influenza Virus and Other Respiratory Viruses in
      a Student Health Care Center through Water-Based Condensation Growth.
AB  - The dynamics and significance of aerosol transmission of respiratory viruses are
      still controversial, for the major reasons that virus aerosols are inefficiently
      collected by commonly used air samplers and that the collected viruses are
      inactivated by the collection method. Without knowledge of virus viability,
      infection risk analyses lack accuracy. This pilot study was performed to (i)
      determine whether infectious (viable) respiratory viruses in aerosols could be
      collected from air in a real world environment by the viable virus aerosol
      sampler (VIVAS), (ii) compare and contrast the efficacy of the standard
      bioaerosol sampler, the BioSampler, with that of the VIVAS for the collection of
      airborne viruses in a real world environment, and (iii) gain insights for the use
      of the VIVAS for respiratory virus sampling. The VIVAS operates via a water vapor
      condensation process to enlarge aerosolized virus particles to facilitate their
      capture. A variety of viable human respiratory viruses, including influenza A
      H1N1 and H3N2 viruses and influenza B viruses, were collected by the VIVAS
      located at least 2 m from seated patients, during a late-onset 2016 influenza
      virus outbreak. Whereas the BioSampler when operated following our optimized
      parameters also collected virus aerosols, it was nevertheless overall less
      successful based on a lower frequency of virus isolation in most cases. This side
      by-side comparison highlights some limitations of past studies based on
      impingement-based sampling, which may have generated false-negative results due
      to either poor collection efficiency and/or virus inactivation due to the
      collection process. IMPORTANCE The significance of virus aerosols in the natural
      transmission of respiratory diseases has been a contentious issue, primarily
      because it is difficult to collect or sample virus aerosols using currently
      available air sampling devices. We tested a new air sampler based on water vapor
      condensation for efficient sampling of viable airborne respiratory viruses in a
      student health care center as a model of a real world environment. The new
      sampler outperformed the industry standard device (the SKC BioSampler) in the
      collection of natural virus aerosols and in maintaining virus viability. These
      results using the VIVAS indicate that respiratory virus aerosols are more
      prevalent and potentially pose a greater inhalation biohazard than previously
      thought. The VIVAS thus appears to be a useful apparatus for microbiology air
      quality tests related to the detection of viable airborne viruses.

PMID- 29034328
TI  - How Should I Submit to mSphere: Traditional, Expedited, or mSphereDirect?

PMID- 29034326
TI  - Bacterial Lipopolysaccharide Destabilizes Influenza Viruses.
AB  - Depending on the specific viral pathogen, commensal bacteria can promote or
      reduce the severity of viral infection and disease progression in their hosts.
      Influenza A virus (IAV) has a broad host range, comprises many subtypes, and
      utilizes different routes of transmission, including the fecal-oral route in wild
      birds. It has been previously demonstrated that commensal bacteria can interact
      with the host's immune system to protect against IAV pathogenesis. However, it is
      unclear whether bacteria and their products may be interacting directly with IAV
      to impact virion stability. Herein we show that gastrointestinal (GI) tract
      bacterial isolates in an in vitro system significantly reduce the stability of
      IAV. Moreover, bacterial lipopolysaccharide (LPS), found on the exterior surfaces
      of bacteria, was sufficient to significantly decrease the stability of both human
      and avian viral strains in a temperature-dependent manner, including at the
      relevant temperatures of their respective hosts and the external aquatic habitat.
      The subtype and host origin of the viruses were shown to affect the extent to
      which IAV was susceptible to LPS. Furthermore, using a receptor binding assay and
      transmission electron microscopy, we observed that LPS binds to and alters the
      morphology of influenza virions, suggesting that direct interaction with the
      viral surface contributes to the observed antiviral effect of LPS on influenza.
      IMPORTANCE Influenza A virus (IAV), transmitted primarily via the fecal-oral
      route in wild birds, encounters high concentrations of bacteria and their
      products. Understanding the extent to which bacteria affect the infectivity of
      IAV will lead to a broader understanding of viral ecology in reservoir hosts and
      may lead to insights for the development of therapeutics in respiratory
      infection. Herein we show that bacteria and lipopolysaccharide (LPS) interact
      with and destabilize influenza virions. Moreover, we show that LPS reduces the
      long-term persistence and freeze-thaw stability of IAV, which is important
      information for modeling the movement and emergence of novel strains from animal
      hosts. Our results, demonstrating that the subtype and host origin of a virus
      also influence its susceptibility to LPS, raise key questions about the fitness
      of viruses in reservoir hosts, their potential to transmit to humans, and the
      importance of bacterial-viral interactions in viral ecology.

PMID- 29034327
TI  - High-Fat Diet Changes Fungal Microbiomes and Interkingdom Relationships in the
      Murine Gut.
AB  - Dietary fat intake and shifts in gut bacterial community composition are
      associated with the development of obesity. To date, characterization of
      microbiota in lean versus obese subjects has been dominated by studies of gut
      bacteria. Fungi, recently shown to affect gut inflammation, have received little
      study for their role in obesity. We sought to determine the effects of high-fat
      diet on fungal and bacterial community structures in a mouse model using the
      internal transcribed spacer region 2 (ITS2) of fungal ribosomal DNA (rDNA) and
      the 16S rRNA genes of bacteria. Mice fed a high-fat diet had significantly
      different abundances of 19 bacterial and 6 fungal taxa than did mice fed standard
      chow, with high-fat diet causing similar magnitudes of change in overall fungal
      and bacterial microbiome structures. We observed strong and complex diet-specific
      coabundance relationships between intra- and interkingdom microbial pairs and
      dramatic reductions in the number of coabundance correlations in mice fed a high
      fat diet compared to those fed standard chow. Furthermore, predicted microbiome
      functional modules related to metabolism were significantly less abundant in high
      fat-diet-fed than in standard-chow-fed mice. These results suggest a role for
      fungi and interkingdom interactions in the association between gut microbiomes
      and obesity. IMPORTANCE Recent research shows that gut microbes are involved in
      the development of obesity, a growing health problem in developed countries that
      is linked to increased risk for cardiovascular disease. However, studies showing
      links between microbes and metabolism have been limited to the analysis of
      bacteria and have ignored the potential contribution of fungi in metabolic
      health. This study provides evidence that ingestion of a high-fat diet is
      associated with changes to the fungal (and bacterial) microbiome in a mouse
      model. In addition, we find that interkingdom structural and functional
      relationships exist between fungi and bacteria within the gut and that these are
      perturbed by high-fat diet.

PMID- 29034329
TI  - Comparative Metabolomics of Mycoplasma bovis and Mycoplasma gallisepticum Reveals
      Fundamental Differences in Active Metabolic Pathways and Suggests Novel Gene
      Annotations.
AB  - Mycoplasmas are simple, but successful parasites that have the smallest genome of
      any free-living cell and are thought to have a highly streamlined cellular
      metabolism. Here, we have undertaken a detailed metabolomic analysis of two
      species, Mycoplasma bovis and Mycoplasma gallisepticum, which cause economically
      important diseases in cattle and poultry, respectively. Untargeted gas
      chromatography-mass spectrometry and liquid chromatography-mass spectrometry
      analyses of mycoplasma metabolite extracts revealed significant differences in
      the steady-state levels of many metabolites in central carbon metabolism, while
      13C stable isotope labeling studies revealed marked differences in carbon source
      utilization. These data were mapped onto in silico metabolic networks predicted
      from genome wide annotations. The analyses elucidated distinct differences,
      including a clear difference in glucose utilization, with a marked decrease in
      glucose uptake and glycolysis in M. bovis compared to M. gallisepticum, which may
      reflect differing host nutrient availabilities. The 13C-labeling patterns also
      revealed several functional metabolic pathways that were previously unannotated
      in these species, allowing us to assign putative enzyme functions to the products
      of a number of genes of unknown function, especially in M. bovis. This study
      demonstrates the considerable potential of metabolomic analyses to assist in
      characterizing significant differences in the metabolism of different bacterial
      species and in improving genome annotation. IMPORTANCE Mycoplasmas are pathogenic
      bacteria that cause serious chronic infections in production animals, resulting
      in considerable losses worldwide, as well as causing disease in humans. These
      bacteria have extremely reduced genomes and are thought to have limited metabolic
      flexibility, even though they are highly successful persistent parasites in a
      diverse number of species. The extent to which different Mycoplasma species are
      capable of catabolizing host carbon sources and nutrients, or synthesizing
      essential metabolites, remains poorly defined. We have used advanced metabolomic
      techniques to identify metabolic pathways that are active in two species of
      Mycoplasma that infect distinct hosts (poultry and cattle). We show that these
      species exhibit marked differences in metabolite steady-state levels and carbon
      source utilization. This information has been used to functionally characterize
      previously unknown genes in the genomes of these pathogens. These species
      specific differences are likely to reflect important differences in host nutrient
      levels and pathogenic mechanisms.

PMID- 29034330
TI  - Perinatal Bisphenol A Exposure Induces Chronic Inflammation in Rabbit Offspring
      via Modulation of Gut Bacteria and Their Metabolites.
AB  - Bisphenol A (BPA) accumulates in the maturing gut and liver in utero and is known
      to alter gut bacterial profiles in offspring. Gut bacterial dysbiosis may
      contribute to chronic colonic and systemic inflammation. We hypothesized that
      perinatal BPA exposure-induced intestinal (and liver) inflammation in offspring
      is due to alterations in the microbiome and colonic metabolome. The 16S rRNA
      amplicon sequencing analysis revealed differences in beta diversity with a
      significant reduction in the relative abundances of short-chain fatty acid (SCFA)
      producers such as Oscillospira and Ruminococcaceae due to BPA exposure.
      Furthermore, BPA exposure reduced fecal SCFA levels and increased systemic
      lipopolysaccharide (LPS) levels. BPA exposure-increased intestinal permeability
      was ameliorated by the addition of SCFA in vitro. Metabolic fingerprints revealed
      alterations in global metabolism and amino acid metabolism. Thus, our findings
      indicate that perinatal BPA exposure may cause gut bacterial dysbiosis and
      altered metabolite profiles, particularly SCFA profiles, leading to chronic colon
      and liver inflammation. IMPORTANCE Emerging evidence suggests that environmental
      toxicants may influence inflammation-promoted chronic disease susceptibility
      during early life. BPA, an environmental endocrine disruptor, can transfer across
      the placenta and accumulate in fetal gut and liver. However, underlying
      mechanisms for BPA-induced colonic and liver inflammation are not fully
      elucidated. In this report, we show how perinatal BPA exposure in rabbits alters
      gut microbiota and their metabolite profiles, which leads to colonic and liver
      inflammation as well as to increased gut permeability as measured by elevated
      serum lipopolysaccharide (LPS) levels in the offspring. Also, perinatal BPA
      exposure leads to reduced levels of gut bacterial diversity and bacterial
      metabolites (short-chain fatty acids [SCFA]) and elevated gut permeability-three
      common early biomarkers of inflammation-promoted chronic diseases. In addition,
      we showed that SCFA ameliorated BPA-induced intestinal permeability in vitro.
      Thus, our study results suggest that correcting environmental toxicant-induced
      bacterial dysbiosis early in life may reduce the risk of chronic diseases later
      in life.

PMID- 29034331
TI  - Extensive Core Microbiome in Drone-Captured Whale Blow Supports a Framework for
      Health Monitoring.
AB  - The pulmonary system is a common site for bacterial infections in cetaceans, but
      very little is known about their respiratory microbiome. We used a small,
      unmanned hexacopter to collect exhaled breath condensate (blow) from two
      geographically distinct populations of apparently healthy humpback whales
      (Megaptera novaeangliae), sampled in the Massachusetts coastal waters off Cape
      Cod (n = 17) and coastal waters around Vancouver Island (n = 9). Bacterial and
      archaeal small-subunit rRNA genes were amplified and sequenced from blow samples,
      including many of sparse volume, as well as seawater and other controls, to
      characterize the associated microbial community. The blow microbiomes were
      distinct from the seawater microbiomes and included 25 phylogenetically diverse
      bacteria common to all sampled whales. This core assemblage comprised on average
      36% of the microbiome, making it one of the more consistent animal microbiomes
      studied to date. The closest phylogenetic relatives of 20 of these core microbes
      were previously detected in marine mammals, suggesting that this core microbiome
      assemblage is specialized for marine mammals and may indicate a healthy,
      noninfected pulmonary system. Pathogen screening was conducted on the microbiomes
      at the genus level, which showed that all blow and few seawater microbiomes
      contained relatives of bacterial pathogens; no known cetacean respiratory
      pathogens were detected in the blow. Overall, the discovery of a shared large
      core microbiome in humpback whales is an important advancement for health and
      disease monitoring of this species and of other large whales. IMPORTANCE The
      conservation and management of large whales rely in part upon health monitoring
      of individuals and populations, and methods generally necessitate invasive
      sampling. Here, we used a small, unmanned hexacopter drone to noninvasively fly
      above humpback whales from two populations, capture their exhaled breath (blow),
      and examine the associated microbiome. In the first extensive examination of the
      large-whale blow microbiome, we present surprising results about the discovery of
      a large core microbiome that was shared across individual whales from
      geographically separated populations in two ocean basins. We suggest that this
      core microbiome, in addition to other microbiome characteristics, could be a
      useful feature for health monitoring of large whales worldwide.

PMID- 29034332
TI  - Bartonella henselae initial infection of mature human erythrocytes observed in
      real time using bacterial endogenous fluorescence.
AB  - Bartonella henselae is a causative agent of anemia, cat scratch disease,
      bacillary angiomatosis, recurrent fever, hepatitis, endocarditis, chronic
      lymphadenopathy, joint and neurological disorders. B. henselae are intra
      erythrocytic bacteria. The goal of this study was to visualize the B. henselae
      invasion into enucleated human red blood cells in real time using bacterium
      endogenous fluorescence. We took advantage of the unique fluorescence emission
      spectral profile of the bacteria. We used a linear unmixing approach to separate
      the fluorescence emission spectra of human erythrocytes from native B. henselae
      when excited at 488nm. Human blood samples were inoculated with B. henselae and
      incubated for 60 hours. 3-D live images were captured at select intervals using
      multi-photon laser scanning microscopy. Uninfected blood samples were also
      analyzed. This study revealed bacteria entering mature erythrocytes over a 60
      hour time period.

PMID- 29034333
TI  - Well-defined nickel and palladium precatalysts for cross-coupling.
AB  - Transition metal-catalysed cross-coupling is one of the most powerful synthetic
      methods and has led to vast improvements in the synthesis of pharmaceuticals,
      agrochemicals and precursors for materials chemistry. A major advance in cross
      coupling over the past 20 years is the utilization of well-defined, bench-stable
      Pd and Ni precatalysts that do not require the addition of free ancillary ligand,
      which can hinder catalysis by occupying open coordination sites on the metal. The
      development of precatalysts has resulted in new reactions and expanded substrate
      scopes, enabling transformations under milder conditions and with lower catalyst
      loadings. This Review highlights recent advances in the development of Pd and Ni
      precatalysts for cross-coupling, and provides a critical comparison between the
      state of the art in Pd- and Ni-based systems.

PMID- 29034335
TI  - Reliability and Validity of the Lichtenberg Financial Decision Screening Scale.
AB  - The scarcity of empirically validated assessment instruments continues to impede
      the work of professionals in a number of fields, including medicine, finance, and
      estate planning; adult protective services; and criminal justice-and, more
      importantly, it impedes their ability to effectively assist and, in some case,
      protect their clients. Other professionals (e.g. legal, financial, medical,
      mental health services) are in a position to prevent financial exploitation and
      would benefit from access to new instruments. The Lichtenberg Financial Decision
      Screening Scale (LFDSS) was introduced in 2016, along with evidence for its
      convergent validity (Lichtenberg et al., 2016). Using a sample of 213
      participants, this study investigated the internal consistency of the LFDSS and
      its criterion validity based on ratings by professionals using the scale. Results
      demonstrate that the LFDSS has excellent internal consistency and clinical
      utility properties. This paper provides support for use of the LFDSS as a
      reliable and valid instrument. The LFDSS and instructions for its use are
      included in the article, along with information about online tools and support.

PMID- 29034334
TI  - Arousal-related adjustments of perceptual biases optimize perception in dynamic
      environments.
AB  - Prior expectations can be used to improve perceptual judgments about ambiguous
      stimuli. However, little is known about if and how these improvements are
      maintained in dynamic environments in which the quality of appropriate priors
      changes from one stimulus to the next. Using a sound-localization task, we show
      that changes in stimulus predictability lead to arousal-mediated adjustments in
      the magnitude of prior-driven biases that optimize perceptual judgments about
      each stimulus. These adjustments depend on task-dependent changes in the
      relevance and reliability of prior expectations, which subjects update using both
      normative and idiosyncratic principles. The resulting variations in biases across
      task conditions and individuals are reflected in modulations of pupil diameter,
      such that larger stimulus-evoked pupil responses correspond to smaller biases.
      These results suggest a critical role for the arousal system in adjusting the
      strength of perceptual biases with respect to inferred environmental dynamics to
      optimize perceptual judgements.

PMID- 29034336
TI  - Occurrence of enrofloxacin in overflows from animal lot and residential sewage
      lagoons and a receiving-stream.
AB  - Enrofloxacin (ENRO), a fluoroquinolone, was quantified in overflows from an
      animal lot and residential sewage lagoons and in a receiving-stream (Gans Creek).
      The concentrations of ENRO in samples was determined by high-performance liquid
      chromatography - tandem mass spectrometry. In total, ninety samples including
      duplicates were analyzed during several monthly sampling campaigns. The samples
      collected represented the residential sewage lagoon overflow (RLO), animal lot
      lagoon overflow (ALLO), the combined overflows (RLO and ALLO), and Gans Creek
      (upstream, midstream and downstream positions). The frequency of detection of
      ENRO was 90% for RLO and 100% for both ALLO and Gans Creek. The highest
      concentration of ENRO (0.44 MUg/L) was found in ALLO sample collected during high
      precipitation. ENRO levels found in RLO samples ranged from < LOQ to 259 ng/L and
      the highest value observed also coincided with high flow. The levels of ENRO
      found in Gans Creek ranged from 17-216 ng/L. A preliminary ecotoxicological
      assessment was conducted through calculation of the risk quotients (RQs) for
      organisms based on the ratio of the measured environmental concentrations in this
      study to the predicted-no-effect-concentrations (acute and chronic effect) data.
      From the RQs, high risks were observed for Microcystis aeruginosa (cyanobacteria;
      RQ = 4.4); Anabaena flosaquae (cyanobacteria; RQ = 1.3); and Lemna minor (aquatic
      vascular plant; RQ = 2.0). The long-term effects of mixtures of PHCs on Gans
      Creek watershed are probable.

PMID- 29034338
TI  - Desorption of harmful hydrocarbon compounds in soil using micron-sized magnetic
      particles and high-frequency magnetic fields.
AB  - This research looks at the use of high frequency (HF) magnetic fields to
      desorb/reduce harmful chemical compounds within gasoline and diesel that commonly
      leak out of underground storage tanks. Using a multi-strand coil design, measured
      magnetic fields of over 3 kilo-amperes per meter are generated at an optimal
      frequency of 117 kHz without skin-depth losses, and without the use of expensive
      super-conductors or liquid-cooled mechanisms. This high frequency magnetic field
      is successfully used in non-contact-based magnetic heating and desorption of
      Gasoline and Diesel mixed with sand, water and easily-dispersible, benign
      micrometer-sized iron filings, used as a magnetic absorber. Gas chromatography
      (GC) tests done on magnetically-heated Gasoline-soil and Diesel-soil mixtures
      show desorption/reduction of gasoline and diesel by 44% and 51% respectively, but
      desorption/reduction of harmful BTEX compounds and other chemical irritants
      within Gasoline and Diesel by 28-66% after only 80 minutes of magnetic heating.
      Review of remediation/desorption methods show magnetic fields fare favorably in
      comparison to other methods that require longer treatment period or the use of
      secondary pollutants at reducing hydrocarbon and BTEX compounds in them.

PMID- 29034339
TI  - A method for the production of large volumes of WAF and CEWAF for dosing
      mesocosms to understand marine oil snow formation.
AB  - Marine oil snow (MOS) formation is a mechanism to transport oil from the ocean
      surface to sediments. We describe here the use of 110L mesocosms designed to
      mimic oceanic parameters during an oil spill including the use of chemical
      dispersants in order to understand the processes controlling MOS formation. These
      experiments were not designed to be toxicity tests but rather to illustrate
      mechanisms. This paper focuses on the development of protocols needed to conduct
      experiments under environmentally relevant conditions to examine marine snow and
      MOS. The experiments required the production of over 500 liters of water
      accommodated fraction (WAF), chemically enhanced water accommodated fraction of
      oil (CEWAF) as well as diluted CEWAF (DCEWAF). A redesigned baffled (170 L)
      recirculating tank (BRT) system was used. Two mesocosm experiments (M1 and M2)
      were run for several days each. In both M1 and M2, marine snow and MOS was formed
      in controls and all treatments respectively. Estimated oil equivalent (EOE)
      concentrations of CEWAF were in the high range of concentrations reported during
      spills and field tests, while WAF and DCEWAF concentrations were within the range
      of concentrations reported during oil spills. EOE decreased rapidly within days
      in agreement with historic data and experiments.

PMID- 29034337
TI  - New biomarkers of post-settlement growth in the sea urchin Strongylocentrotus
      purpuratus.
AB  - Some sea urchins, including the purple sea urchin Strongylocentrotus purpuratus,
      have been successfully used in aquaculture, but their slow growth and late
      reproduction are challenging to overcome when developing efficient aquaculture
      production techniques. S. purpuratus develops via an indirect life history that
      is characterized by a drastic settlement process at the end of a larval period
      that lasts for several weeks. During this transition, the bilateral larva is
      transformed into a pentaradial juvenile, which will start feeding and growing in
      the benthic habitat. Due to predation and other ecological factors, settlement is
      typically associated with high mortality rates in juvenile populations.
      Additionally, juveniles require several days to develop a functional mouth and
      digestive system. During this perimetamorphic period, juveniles use up larval
      resources until they are capable to digest adult food. Mechanisms underlying the
      onset of juvenile feeding and metabolism have implications for the recruitment of
      natural populations as well as aquaculture and are relatively poorly understood
      in S. purpuratus. The insulin/insulin-like growth factor signalling (IIS)/Target
      of Rapamycin (TOR) pathway (IIS/TOR) is well conserved among animal phyla and
      regulates physiological and developmental functions, such as growth,
      reproduction, aging and nutritional status. We analyzed the expression of FoxO,
      TOR, and ILPs in post-settlement juveniles in conjunction with their early growth
      trajectories. We also tested how pre-settlement starvation affected post
      settlement expression of IIS. We found that FoxO provides a useful molecular
      marker in early juveniles as its expression is strongly correlated with juvenile
      growth. We also found that pre-settlement starvation affects juvenile growth
      trajectories as well as IIS. Our findings provide preliminary insights into the
      mechanisms underlying post-settlement growth and metabolism in S. purpuratus.
      They also have important implications for sea urchin aquaculture, as they show
      that pre-settlement nutrient environment significantly affects both early growth
      trajectories and gene expression. This information can be used to develop new
      biomarkers for juvenile health in sea urchin population ecology and aquaculture
      aquaculture.

PMID- 29034340
TI  - Titanium addition influences antibacterial activity of bioactive glass coatings
      on metallic implants.
AB  - In an attempt to combat the possibility of bacterial infection and insufficient
      bone growth around metallic, surgical implants, bioactive glasses may be employed
      as coatings. In this work, silica-based and borate-based glass series were
      synthesized for this purpose and subsequently characterized in terms of
      antibacterial behavior, solubility and cytotoxicity. Borate-based glasses were
      found to exhibit significantly superior antibacterial properties and increased
      solubility compared to their silica-based counterparts, with BRT0 and BRT3
      (borate-based glasses with 0 and 15 mol% of titanium dioxide incorporated,
      respectively) outperforming the remainder of the glasses, both borate and
      silicate based, in these respects. Atomic Absorption Spectroscopy confirmed the
      release of zinc ions (Zn2+), which has been linked to the antibacterial abilities
      of glasses SRT0, BRT0 and BRT3, with inhibition effectively achieved at
      concentrations lower than 0.7 ppm. In vitro cytotoxicity studies using MC3T3-E1
      osteoblasts confirmed that cell proliferation was affected by all glasses in this
      study, with decreased proliferation attributed to a faster release of sodium ions
      over calcium ions in both glass series, factor known to slow cell proliferation
      in vitro.

PMID- 29034341
TI  - Paclitaxel induces Stathmin 1 phosphorylation, microtubule stability and
      apoptosis in acute lymphoblastic leukemia cells.
AB  - Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by
      abnormal proliferation and accumulation of lymphoblasts in the hematopoietic
      system. Stathmin 1 is a proliferation marker for normal lymphocytes, which has
      been described as highly expressed in ALL patients and functionally important for
      leukemia phenotype. In the present study, we expand our previous observations and
      aim to investigate Stathmin 1 expression and its impact on laboratory features
      and clinical outcomes in an independent cohort of ALL patients, and to verify the
      effects of paclitaxel treatment on Stathmin 1 phosphorylation and cell viability
      in ALL cell lines. In ALL patients, Stathmin 1 expression was significantly
      increased, associated with lower age onset and positively correlated with white
      blood cell counts, but did not impact on clinical outcomes. Functional assays
      revealed that paclitaxel induces Stathmin 1 phosphorylation at serine 16 (an
      inhibitory site), microtubule stability and apoptosis in Jurkat and Namalwa cell
      lines. Paclitaxel treatment did not modulate cell viability of normal peripheral
      blood leukocytes. In conclusion, our data confirm increased levels of Stathmin 1
      in ALL patients and that therapeutic doses of paclitaxel inhibits Stathmin 1
      function and promote microtubule stability and apoptosis in ALL cells.

PMID- 29034343
TI  - Regarding the applications of fusion-fluorescence imaging using indocyanine green
      in laparoscopic hepatectomy.

PMID- 29034342
TI  - p16(INK4A) expression in invasive laryngeal cancer.
AB  - We examined p16 expression in tumors from a population-based sample of laryngeal
      cancer cases diagnosed in the U.S. Samples had been previously genotyped for HPV
      DNA. Overall, p16 expression was observed in laryngeal tissue from 8 of 101
      (7.9%) cases. p16 expression was observed in 2 of 16 (12.5%) cases previously
      determined to be HPV DNA positive. The two cases dually positive for p16 and HPV
      DNA were non-keratinizing SCC and papillary SCC tumors that were positive for
      genotypes 18 and 35/89, respectively. Positivity for p16 and/or HPV DNA was not
      associated with 5-year survival (log-rank p value= 0.55). Our findings support a
      limited role of HPV in laryngeal carcinogenesis. p16 is not a reliable surrogate
      for HPV status in laryngeal cancers and is not a predictor of laryngeal cancer
      survival.

PMID- 29034344
TI  - Hemocoagulase might not control but worsen gastrointestinal bleeding in an
      elderly patient with type II respiratory failure.
AB  - Hemocoagulase has been successfully used for the management of bleeding in
      patients undergoing surgery. Local spray of hemocoagulase during endoscopic
      therapy may be effective for the management of gastrointestinal bleeding. In
      China, intravenous infusion of hemocoagulase is given by some physicians for the
      treatment of gastrointestinal bleeding. However, the potential adverse events
      secondary to hemocoagulase, such as hypofibrinogenemia, are poorly recognized. In
      this paper, we reported an elderly patient with type II respiratory failure in
      whom hemocoagulase might induce hypofibrinogenemia and further worsen
      gastrointestinal bleeding. We highlighted that fibrinogen levels should be
      cautiously monitored in patients receiving hemocoagulase.

PMID- 29034346
TI  - Enlarged selection criteria for hepatocellular cancer: is the upper limit needed?
AB  - Liver transplantation (LT) for hepatocellular carcinoma (HCC) is strategically
      challenging because the very good mid-term outcomes of this treatment jar with
      the risk of cancer recurrence. Although Milan criteria (MC) tap the balance on
      the safe side, they tend to be considered too restrictive and new, enlarged
      criteria have been conceived in order to enlarge the pool of potential
      recipients. Some extended criteria are more audacious then others, but they seem
      to be well tailored on the local reality they are applied to. Being HCC
      epidemiology and organs availability very variable between regions, a universally
      valid 'upper limit' is yet to be determinable.

PMID- 29034345
TI  - The growing impact of alpha-fetoprotein in the field of liver transplantation for
      hepatocellular cancer: time for a revolution.
AB  - The role of alpha-fetoprotein (AFP) in the specific setting of the diagnosis and
      prognosis of patients with hepatocellular cancer (HCC) waiting for liver
      transplantation (LT) is still controversial. Recently, a marked interest for this
      marker has been reported, mainly related to its ability to predict the outcome of
      HCC patients after LT. The growing number of papers in PubMed indicates that AFP
      has begun a "second life" in the particular context of LT. Looking at the most
      recent International Guidelines on HCC, it looks obvious that time is ripe to
      reevaluate the value of AFP in relation to its prognostic ability to identify HCC
      patients at high-risk for drop-out before and recurrence after LT. Many
      discrepancies exist worldwide regarding the use of biomarkers in HCC. In contrast
      to the Western world, AFP is widely used in Asian countries, the reason why being
      unclear. Indeed, in the (merely Western-dominated) HCC treatment algorithms, the
      role of AFP as a prognostic tumor marker is still considered to be "under
      investigation". One should however realize that the underestimation of the value
      of AFP in the LT context will hamper further refinements of both the liver
      allograft allocation process and the selection of the best candidates for this
      procedure. Moreover, AFP has an important role to play in the monitoring of
      bridging and/or downstaging procedures bringing eventually the patient to
      transplantation. So, time has come to reconsider the role and value of AFP
      (dynamics) in the field of transplant oncology.

PMID- 29034347
TI  - Using a weaning immunosuppression protocol in liver transplantation recipients
      with hepatocellular carcinoma: a compromise between the risk of recurrence and
      the risk of rejection?
AB  - Hepatocellular carcinoma (HCC) recurrence rate after liver transplantation (LT)
      is still up to 15-20%, despite a careful selection of candidates and optimization
      of the management within the waiting list. To reduce tumour recurrence, the
      currently adopted post-transplant strategies are based on the administration of a
      tailored immunosuppression (IS) regimen. Drug-induced depression of the immune
      system is essential in preventing graft rejection, however has a well-established
      association with oncogenesis. The immune system has a key role as a defending
      mechanism against cancer development, preventing vascular invasion and
      metastasis. Thus, IS drugs represent one of few modifiable non-oncological risk
      factors for tumour recurrence. In HCC recipients, a tailored IS therapy, with the
      aim to minimize drugs' doses, is essential to gain the optimal balance between
      the risk of rejection and the risk of tumour recurrence. So far, a complete
      withdrawal of IS drugs after LT is reported to be safely achievable in 25% of
      patients (defined as "operational tolerant"), without the risk of patient and
      graft loss. The recent identification of non-invasive "bio-markers of tolerance",
      which permit to identify patients who could successfully withdraw IS therapies,
      opens new perspectives in the management of HCC after LT. IS withdrawal could
      potentially reduce the risk of tumour recurrence, which represents the major
      drawback in HCC recipients. Herein, we review the current literature on IS
      weaning in patients who underwent LT for HCC as primary indication and we report
      the largest experiences on IS withdrawal in HCC recipients.

PMID- 29034348
TI  - Selection of patients with hepatocellular cancer: a difficult balancing between
      equity, utility, and benefit.
AB  - Although liver transplantation (LT) represents the gold-standard strategy for
      hepatocellular cancer (HCC), its use is circumscribed by several factors like
      donor shortage, perioperative complications, or competition with other candidates
      without HCC. Moreover, different alternative approaches like resection or loco
      regional therapies may be attempted in selected cases. The best option for the
      treatment of an HCC patient is a complex decision, involving several ethical
      principles including: equity (horizontal equity and vertical equity or urgency),
      and utility. These principles influence the different phases of the patient
      selection process for LT: inscription in the waiting list (WL), deciding upon
      patient priority and drop-out before LT, allocating the liver donor to the best
      matched recipient. The best end-point for describing the principle of utility is
      the "transplant benefit" (TB). This concept expresses the survival gain obtained
      comparing LT with the best alternative therapies (i.e., difference between life
      years obtained with and without LT). The TB used with a mid-term time horizon
      (post-transplant 5-10 years), has the intrinsic potential to reach the dignity of
      an independent LT selection principle. Thus, the present review investigates the
      role of organ allocation using a TB model with the intent to introduce equity
      among patients transplanted having HCC or non-tumoral diseases.

PMID- 29034349
TI  - Future applications of fusion-fluorescence imaging during laparoscopic
      procedures.

PMID- 29034350
TI  - Function-preserving surgery for gastric cancer: current status and future
      perspectives.
AB  - The number of early gastric cancer (EGC) cases has been increasing because of
      improved diagnostic procedures including endoscopy and screening systems.
      Therefore, function-preserving gastrectomy (FPG) for EGC with the expectation of
      better quality of life (QOL) after surgery may be increasingly utilized, due to
      its association with low rate of lymph node metastasis and excellent survival and
      the possibility of employing less invasive procedures such as laparoscopic
      gastrectomy in combination. Pylorus-preserving gastrectomy (PPG) with curative
      intent lymph node dissection is a representative FPG that has been used in EGC,
      and its superiorities, indications, limitations, and survival benefits have
      already been reported in several retrospective studies. Laparoscopic proximal
      gastrectomy (LAPG) has also been employed in EGC of the upper third of the
      stomach; however, LAPG was found to be associated with major issues in achieving
      a balance between swallowing and reflux prevention. In patients with EGC in the
      upper third of the stomach, laparoscopy-assisted subtotal gastrectomy with a
      preserved, albeit very small, stomach may provide a better QOL and fewer
      postoperative complications. FPG is recommended as a surgical treatment for EGC
      if the indication is accurately diagnosed and strictly confirmed; however, these
      techniques in laparoscopic surgery present technical difficulties to surgeons
      without a certain degree of skills. Although many retrospective studies revealed
      the functional benefits or oncological safety with FPG, further prospective
      studies using large case series are necessary to reveal the value of FPG compared
      with the conventional procedures.

PMID- 29034351
TI  - Bridging patients with hepatocellular cancer waiting for liver transplant: all
      the patients are the same?
AB  - Liver transplant (LT) is considered the best curative treatment for patients with
      cirrhosis and hepatocellular carcinoma (HCC) within Milan criteria. The
      possibility to perform LT in HCC patients is limited by the liver grafts supply;
      indeed, the shortage of donors often leads to a long time on waiting list and
      then to dropout because of tumor progression. Bridging therapies are neo-adjuvant
      treatments given to patients on LT waitlist, with the aim to prevent tumor
      progression and to reduce dropout rate. Many bridging modalities have been
      proposed. The choice of each treatment is based on the characteristics of the
      patient, liver function, comorbidities and on the number, dimensions and
      localization of HCC. This review article describes several types of bridging
      therapies, focusing on the indications for different kind of patients.

PMID- 29034352
TI  - Screening endoscopy for gastric cancer: time for quality control.

PMID- 29034354
TI  - Prefrontal Connectivity and Glutamate Transmission: Relevance to Depression
      Pathophysiology and Ketamine Treatment.
AB  - BACKGROUND: Prefrontal global brain connectivity with global signal regression
      (GBCr) was proposed as a robust biomarker of depression, and was associated with
      ketamine's mechanism of action. Here, we investigated prefrontal GBCr in
      treatment-resistant depression (TRD) at baseline and following treatment. Then,
      we conducted a set of pharmacological challenges in healthy subjects to
      investigate the glutamate neurotransmission correlates of GBCr. METHODS: In study
      A, we used functional magnetic resonance imaging (fMRI) to compare GBCr between
      22 TRD and 29 healthy control. Then, we examined the effects of ketamine and
      midazolam on GBCr in TRD patients 24h post-treatment. In study B, we acquired
      repeated fMRI in 18 healthy subjects to determine the effects of lamotrigine (a
      glutamate release inhibitor), ketamine, and lamotrigine-by-ketamine interaction.
      RESULTS: In study A, TRD patients showed significant reduction in dorsomedial and
      dorsolateral prefrontal GBCr compared to healthy control. In TRD patients, GBCr
      in the altered clusters significantly increased 24h following ketamine (effect
      size = 1.0 [0.3 1.8]), but not midazolam (effect size = 0.5 [-0.6 1.3]). In study
      B, oral lamotrigine reduced GBCr 2h post-administration, while ketamine increased
      medial prefrontal GBCr during infusion. Lamotrigine significantly reduced the
      ketamine-induced GBCr surge. Exploratory analyses showed elevated ventral
      prefrontal GBCr in TRD and significant reduction of ventral prefrontal GBCr
      during ketamine infusion in healthy subjects. CONCLUSIONS: This study provides
      first replication of the ability of ketamine to normalize depression-related
      prefrontal dysconnectivity. It also provides indirect evidence that these effects
      may be triggered by the capacity of ketamine to enhance glutamate
      neurotransmission.

PMID- 29034353
TI  - The Default Mode Network in Autism.
AB  - Autism spectrum disorder (ASD) is characterized by deficits in social
      communication and interaction. Since its discovery as a major functional brain
      system, the default mode network (DMN) has been implicated in a number of
      psychiatric disorders, including ASD. Here we review converging multimodal
      evidence for DMN dysfunction in the context of specific components of social
      cognitive dysfunction in ASD: 'self-referential processing' - the ability to
      process social information relative to oneself and 'theory of mind' or
      'mentalizing' - the ability to infer the mental states such as beliefs,
      intentions, and emotions of others. We show that altered functional and
      structural organization of the DMN, and its atypical developmental trajectory,
      are prominent neurobiological features of ASD. We integrate findings on atypical
      cytoarchitectonic organization and imbalance in excitatory-inhibitory circuits,
      which alter local and global brain signaling, to scrutinize putative mechanisms
      underlying DMN dysfunction in ASD. Our synthesis of the extant literature
      suggests that aberrancies in key nodes of the DMN and their dynamic functional
      interactions contribute to atypical integration of information about the self in
      relation to 'other', as well as impairments in the ability to flexibly attend to
      socially relevant stimuli. We conclude by highlighting open questions for future
      research.

PMID- 29034355
TI  - Vitreous Disease in Retinoblastoma: Clinical Findings and Treatment.

PMID- 29034357
TI  - Troponin release following brief myocardial ischemia: apoptosis versus necrosis.

PMID- 29034356
TI  - Renal Denervation Reduces Pulmonary Vascular Remodeling and Right Ventricular
      Diastolic Stiffness in Experimental Pulmonary Hypertension.
AB  - Neurohormonal overactivation plays an important role in pulmonary hypertension
      (PH). In this context, renal denervation, which aims to inhibit the neurohormonal
      systems, may be a promising adjunct therapy in PH. In this proof-of-concept
      study, we have demonstrated in 2 experimental models of PH that renal denervation
      delayed disease progression, reduced pulmonary vascular remodeling, lowered right
      ventricular afterload, and decreased right ventricular diastolic stiffness, most
      likely by suppression of the renin-angiotensin-aldosterone system.

PMID- 29034360
TI  - DEVELOPING COMPLETE ULTRASONIC MANAGEMENT OF KIDNEY STONES FOR SPACEFLIGHT.
AB  - Bone demineralization, dehydration, and stasis put astronauts at an increased
      risk of forming kidney stones in space. The incidence of kidney stones and the
      potential for a mission-critical event are expected to rise as expeditions become
      longer and immediate transport to Earth becomes more problematic. At the
      University of Washington, we are developing an ultrasound-based stone management
      system to detect stones with S-modeTM ultrasound imaging, break stones with burst
      wave lithotripsy (BWLTM), and reposition stones with ultrasonic propulsion (UPTM)
      on Earth and in space. This review discusses the development and current state of
      these technologies, as well as integration on the flexible ultrasound system
      sponsored by NASA and the National Space Biomedical Research Institute.

PMID- 29034359
TI  - The Definition, Rationale, and Effects of Thresholding in OCT Angiography.
AB  - PURPOSE: To examine the definition, rationale, and effects of thresholding in OCT
      angiography (OCTA). DESIGN: A theoretical description of OCTA thresholding in
      combination with qualitative and quantitative analysis of the effects of OCTA
      thresholding in eyes from a retrospective case series. PARTICIPANTS: Four eyes
      were qualitatively examined: 1 from a 27-year-old control, 1 from a 78-year-old
      exudative age-related macular degeneration (AMD) patient, 1 from a 58-year-old
      myopic patient, and 1 from a 77-year-old nonexudative AMD patient with geographic
      atrophy (GA). One eye from a 75-year-old nonexudative AMD patient with GA was
      quantitatively analyzed. MAIN OUTCOME MEASURES: A theoretical thresholding model
      and a qualitative and quantitative description of the dependency of OCTA on
      thresholding level. RESULTS: Due to the presence of system noise, OCTA
      thresholding is a necessary step in forming OCTA images; however, thresholding
      can complicate the relationship between blood flow and OCTA signal. CONCLUSIONS:
      Thresholding in OCTA can cause significant artifacts, which should be considered
      when interpreting and quantifying OCTA images.

PMID- 29034361
TI  - THE CRITICAL ROLE OF NONHUMAN PRIMATES IN MEDICAL RESEARCH.

PMID- 29034358
TI  - Acute Kidney Injury Recognition in Low- and Middle-Income Countries.
AB  - Acute kidney injury (AKI) is increasingly common around the world. Because of the
      low availability of effective therapies and resource limitations, early
      preventive and therapeutic measures are essential to decrease morbidity,
      mortality, and cost. Timely recognition and diagnosis of AKI requires a
      heightened degree of suspicion in the appropriate clinical and environmental
      context. In low- and middle-income countries (LMICs), early detection is impaired
      by limited resources and low awareness. In this article, we report the consensus
      recommendations of the 18th Acute Dialysis Quality Initiative meeting in
      Hyderabad, India, on how to improve recognition of AKI. We expect these
      recommendations will lead to an earlier and more accurate diagnosis of AKI, and
      improved research to promote a better understanding of the epidemiology,
      etiology, and histopathology of AKI in LMICs.

PMID- 29034363
TI  - Nocebo effects in clinical studies: hints for pain therapy.
AB  - INTRODUCTION: Nocebo-induced algesic responses occurring within clinical contexts
      present a challenge for health care practitioners working in the field of pain
      medicine. OBJECTIVES: Following the recent research on algesic nocebo effects,
      the scope of this review is to develop ethically acceptable strategies to help
      avoid, or at least reduce, nocebo responses within clinical settings. METHODS: We
      reviewed relevant clinical studies that depict how patient-practitioner
      interactions may contribute to the reduction of nocebo responses. RESULTS: A
      strong algesic nocebo effect may adversely impact a patient's condition by
      causing decreases in both the efficacy and effectiveness of interventions, as
      well as by promoting treatment nonadherence and discontinuation. These effects
      may be triggered through multiple channels and can lead to significant
      alterations in a patient's perception of pain, consequently producing a weakening
      of the specific positive effects of pharmacological, psychological, or physical
      pain-management interventions. CONCLUSION: To minimize nocebo effects in clinical
      settings, we identified and discussed five contextual aspects relevant to the
      treatment of patients with chronic pain: (1) negative patient-clinician
      communication and interaction during treatment; (2) emotional burden of patients
      during treatment with analgesic medication; (3) negative information provided via
      informational leaflets; (4) cued and contextual conditioning nocebo effects; and
      (5) patient's lack of positive information. Through an understanding of these
      elements, many preventive and ethically acceptable clinical actions can be taken
      to improve multidisciplinary pain treatment outcomes.

PMID- 29034362
TI  - Lipid droplets, potential biomarker and metabolic target in glioblastoma.
AB  - Lipid droplets (LDs) are subcellular organelles that store large amounts of the
      neutral lipids, triglycerides (TG) and/or cholesteryl esters (CE). LDs are
      commonly formed in adipocytes, liver cells and macrophages, and their formation
      has been shown to be associated with the progression of metabolic diseases, i.e.,
      obesity, fatty liver and atherosclerosis. Interestingly, LDs are also found in
      some tumor tissues. We recently showed that LDs are prevalent in glioblastoma
      (GBM), the most deadly brain tumor, but are not detectable in low-grade gliomas
      and normal brain tissues, suggesting that LDs may serve as a novel diagnostic
      biomarker for GBM. This short review will briefly introduce LD biology, summarize
      recent observations about LDs in several types of cancer tissues, and discuss LD
      formation in GBM. Moreover, we will highlight the role of SOAT1 (sterol-O
      transferase 1), a key enzyme regulating CE synthesis and LD formation in GBM, in
      the regulation of SREBP (sterol regulatory-element binding protein) activation.
      The therapeutic potential of LDs and SOAT1 will be discussed.

PMID- 29034364
TI  - Microenvironmental agonists generate de novo phenotypic resistance to combined
      ibrutinib plus venetoclax in CLL and MCL.
AB  - De novo resistance and rapid recurrence often characterize responses of B-cell
      malignancies to ibrutinib (IBR), indicating a need to develop drug combinations
      that block compensatory survival signaling and give deeper, more durable
      responses. To identify such combinations, we previously performed a combinatorial
      drug screen and identified the Bcl-2 inhibitor venetoclax (VEN) as a promising
      partner for combination with IBR in Mantle Cell Lymphoma (MCL). We have opened a
      multi-institutional clinical trial to test this combination. However, analysis of
      primary samples from patients with MCL as well as chronic lymphocytic leukemia
      (CLL) revealed unexpected heterogeneous de novo resistance even to the IBR+VEN
      combination. In the current study, we demonstrate that resistance to the
      combination can be generated by microenvironmental agonists: IL-10, CD40L and,
      most potently, CpG-oligodeoxynucleotides (CpG-ODN), which is a surrogate for
      unmethylated DNA and a specific agonist for TLR9 signaling. Incubation with these
      agonists caused robust activation of NF-kappaB signaling, especially alternative
      NF-kappaB, which led to enhanced expression of the anti-apoptotic proteins Mcl-1,
      Bcl-xL, and survivin, thus decreasing dependence on Bcl-2. Inhibitors of NF
      kappaB signaling blocked overexpression of these anti-apoptotic proteins and
      overcame resistance. Inhibitors of Mcl-1, Bcl-xL, or survivin also overcame this
      resistance, and showed synergistic benefit with the IBR+VEN combination. We
      conclude that microenvironmental factors, particularly the TLR9 agonist, can
      generate de novo resistance to the IBR+VEN combination in CLL and MCL cells. This
      signaling pathway presents targets for overcoming drug resistance induced by
      extrinsic microenvironmental factors in diverse B-cell malignancies.

PMID- 29034365
TI  - Ethnicity, sex, and age are determinants of red blood cell storage and stress
      hemolysis: results of the REDS-III RBC-Omics study.
AB  - Genetic polymorphisms in blood donors may contribute to donor-specific
      differences in the survival of red blood cells (RBCs) during cold storage and
      after transfusion. Genetic variability is anticipated to be high in donors with
      racial admixture from malaria endemic regions such as Africa and Asia. The
      purpose of this study was to test the hypothesis that donor genetic background,
      reflected by sex and self-reported ethnicity, significantly modulates RBC
      phenotypes in storage. High throughput hemolysis assays were developed and used
      to evaluate stored RBC samples from 11 115 African American, Asian, white, and
      Hispanic blood donors from 4 geographically diverse regions in the United States.
      Leukocyte-reduced RBC concentrate-derived samples were stored for 39 to 42 days
      (1-6 degrees C) and then evaluated for storage, osmotic, and oxidative hemolysis.
      Male sex was strongly associated with increased susceptibility to all 3 hemolysis
      measures (P < .0001). African American background was associated with resistance
      to osmotic hemolysis compared with other racial groups (adjusted P < .0001).
      Donor race/ethnicity was also associated with extreme (>1%) levels of storage
      hemolysis exceeding US Food and Drug Administration regulations for transfusion
      (hemolysis >1% was observed in 3.51% of Asian and 2.47% of African American
      donors vs 1.67% of white donors). These findings highlight the impact of donor
      genetic traits on measures of RBC hemolysis during routine cold storage, and they
      support current plans for genome-wide association studies, which may help
      identify hereditable variants with substantive effects on RBC storage stability
      and possibly posttransfusion outcomes.

PMID- 29034367
TI  - Physical Exercise Interventions for Drug Addictive Disorders.

PMID- 29034368
TI  - Solar-Driven Thermochemical Splitting of CO2 and In Situ Separation of CO and O2
      across a Ceria Redox Membrane Reactor.
AB  - Splitting CO2 with a thermochemical redox cycle utilizes the entire solar
      spectrum and provides a favorable path to the synthesis of solar fuels at high
      rates and efficiencies. However, the temperature/pressure swing commonly applied
      between reduction and oxidation steps incurs irreversible energy losses and
      severe material stresses. Here, we experimentally demonstrate for the first time
      the single-step continuous splitting of CO2 into separate streams of CO and O2
      under steady-state isothermal/isobaric conditions. This is accomplished using a
      solar-driven ceria membrane reactor conducting oxygen ions, electrons, and
      vacancies induced by the oxygen chemical potential gradient. Guided by the
      limitations imposed by thermodynamic equilibrium of CO2 thermolysis, we operated
      the solar reactor at 1,600 degrees C, 3.10-6 bar [Formula: see text] and 3,500
      suns radiation, yielding total selectivity of CO2 to CO + 1/2O2 with a conversion
      rate of 0.024 MUmol.s-1 per cm2 membrane. The dynamics of the oxygen vacancy
      exchange, tracked by GC and XPS, further validated stable fuel production.

PMID- 29034366
TI  - A phase 2 study incorporating sorafenib into the chemotherapy for older adults
      with FLT3-mutated acute myeloid leukemia: CALGB 11001.
AB  - The Cancer and Leukemia Group B (CALGB), now part of the Alliance for Clinical
      Trials in Oncology, conducted a multicenter, single-arm, phase 2 study in
      patients >=60 years with FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid
      leukemia (AML). In this study, sorafenib was added to daunorubicin and cytarabine
      based induction and consolidation chemotherapy and was also continued for 12
      months of maintenance therapy. The primary end point of the study was overall
      survival (OS) at 1 year in the FLT3 internal tandem duplication (FLT3-ITD)
      cohort. Fifty-four patients with a median age of 67 years (range, 60.3-82.7
      years) were enrolled; 39 were FLT3-ITD patients (71%) and 15 were FLT3-TKD (29%)
      patients. The observed 1-year OS (95% confidence interval [CI]) was 62% (45%-78%)
      for the FLT3-ITD patients (meeting the primary end point 62% vs 30% for a
      historical control group, P < .0001) and 71% (42%-92%) for the FLT3-TKD patients.
      The median disease-free survival and OS were 12.2 months (95% CI, 5-16.9) and
      15.0 months (95% CI, 10.4-20.1), respectively, in the FLT3-ITD group and 9.6 (95%
      CI, 1.9 to not available [NA]) and 16.2 months (95% CI, 5.0 to NA) for the FLT3
      TKD group. This study suggests that the addition of sorafenib to chemotherapy for
      FLT3-ITD AML is feasible and may improve the survival of older adults with FLT3
      mutated AML. This trial was registered at www.clinicaltrials.gov as #NCT01253070.

PMID- 29034369
TI  - Alpha 1 Microglobulin: A Potentially Paradoxical Anti-Oxidant Agent.
AB  - Alpha 1 microglobulin is a low molecular weight heme binding antioxidant protein
      with interesting, and potentially important, clinical applications. However, much
      remains to be learned about its in vivo effects. This invited review raises a
      number of physiologic issues regarding this compound as it pertains to clinical
      use.

PMID- 29034370
TI  - A Robust Energy Minimization Algorithm for MS-Lesion Segmentation.
AB  - The detection of multiple sclerosis lesion is important for many neuroimaging
      studies. In this paper, a new automatic robust algorithm for lesion segmentation
      based on MR images is proposed. This method takes full advantage of the
      decomposition of MR images into the true image that characterizes a physical
      property of the tissues and the bias field that accounts for the intensity
      inhomogeneity. An energy function is defined in term of the property of true
      image and bias field. The energy minimization is proposed for seeking the optimal
      segmentation result of lesions and white matter. Then postprocessing operations
      is used to select the most plausible lesions in the obtained hyperintense
      signals. The experimental results show that our approach is effective and robust
      for the lesion segmentation.

PMID- 29034371
TI  - Assessing Behavioral Stages From Social Media Data.
AB  - Important work rooted in psychological theory posits that health behavior change
      occurs through a series of discrete stages. Our work builds on the field of
      social computing by identifying how social media data can be used to resolve
      behavior stages at high resolution (e.g. hourly/daily) for key population
      subgroups and times. In essence this approach opens new opportunities to advance
      psychological theories and better understand how our health is shaped based on
      the real, dynamic, and rapid actions we make every day. To do so, we bring
      together domain knowledge and machine learning methods to form a hierarchical
      classification of Twitter data that resolves different stages of behavior. We
      identify and examine temporal patterns of the identified stages, with alcohol as
      a use case (planning or looking to drink, currently drinking, and reflecting on
      drinking). Known seasonal trends are compared with findings from our methods. We
      discuss the potential health policy implications of detecting high frequency
      behavior stages.

PMID- 29034372
TI  - Denoising Diffusion-Weighted Images Using Grouped Iterative Hard Thresholding of
      Multi-Channel Framelets.
AB  - Noise in diffusion-weighted (DW) images increases the complexity of quantitative
      analysis and decreases the reliability of inferences. Hence, to improve analysis,
      it is often desirable to remove noise and at the same time preserve relevant
      image features. In this paper, we propose a tight wavelet frame based approach
      for edge-preserving denoising of DW images. Our approach (i) employs the unitary
      extension principle (UEP) to generate frames that are discrete analogues to
      differential operators of various orders; (ii) introduces a very efficient method
      for solving an l0 denoising problem that involves only thresholding and solving a
      trivial inverse problem; and (iii) groups DW images acquired with neighboring
      gradient directions for collaborative denoising. Experiments using synthetic data
      with noncentral chi noise and real data with repeated scans confirm that our
      method yields superior performance compared with denoising using state-of-the-art
      methods such as non-local means.

PMID- 29034373
TI  - Guiding AKI Prevention Using Biomarkers.

PMID- 29034374
TI  - Suicide Attempts among Latinas who Experienced Early Sex Were Largely Mediated by
      Substance Abuse.
AB  - The purpose of this study was to describe the role of substance abuse as a
      mediating factor between early sexual experiences and suicide attempts among
      adult Latinas. In our study participants (n=158), nearly 15% had attempted
      suicide and 39% experienced their first sexual encounter at an age of 15 or
      younger (referred to hereafter as "early sex"). Latinas who experienced early sex
      were more likely to attempt suicide [OR=2.4, p<0.05], and this relationship was
      largely mediated by substance abuse. An early sexual debut may indicate an
      environmental adversity on the child that calls for long term intervention for
      prevention of substance abuse as well as promotion of psychological well-being
      later in life.

PMID- 29034375
TI  - Extracting Drug-Drug Interactions with Word and Character-Level Recurrent Neural
      Networks.
AB  - Drug-drug interactions (DDIs) are known to be responsible for nearly a third of
      all adverse drug reactions. Hence several current efforts focus on extracting
      signal from EMRs to prioritize DDIs that need further exploration. To this end,
      being able to extract explicit mentions of DDIs in free text narratives is an
      important task. In this paper, we explore recurrent neural network (RNN)
      architectures to detect and classify DDIs from unstructured text using the
      DDIExtraction dataset from the SemEval 2013 (task 9) shared task. Our methods are
      in line with those used in other recent deep learning efforts for relation
      extraction including DDI extraction. However, to our knowledge, we are the first
      to investigate the potential of character-level RNNs (Char-RNNs) for DDI
      extraction (and relation extraction in general). Furthermore, we explore a simple
      but effective model bootstrapping method to (a). build model averaging ensembles,
      (b). derive confidence intervals around mean micro-F scores (MMF), and (c).
      assess the average behavior of our methods. Without any rule based filtering of
      negative examples, a popular heuristic used by most earlier efforts, we achieve
      an MMF of 69.13. By adding simple replicable heuristics to filter negative
      instances we are able to achieve an MMF of 70.38. Furthermore, our best ensembles
      produce micro F-scores of 70.81 (without filtering) and 72.13 (with filtering),
      which are superior to metrics reported in published results. Although Char-RNNs
      turnout to be inferior to regular word based RNN models in overall comparisons,
      we find that ensembling models from both architectures results in nontrivial
      gains over simply using either alone, indicating that they complement each other.

PMID- 29034376
TI  - Exploring the Pregnant Guinea Pig as a Model for Group B Streptococcus
      Intrauterine Infection.
AB  - Infection of the amniotic cavity remains a major cause of preterm birth,
      stillbirth, fetal injury and early onset, fulminant infections in newborns.
      Currently, there are no effective therapies to prevent in utero infection and
      consequent co-morbidities. This is in part due to the lack of feasible and
      appropriate animal models to understand mechanisms that lead to in utero
      infections. Use of mouse and rat models do not fully recapitulate human
      pregnancy, while pregnant nonhuman primate models are limited by ethical
      considerations, technical constraints, and cost. Given these limitations, the
      guinea pig is an attractive animal model for studying pregnancy infections,
      particularly as the placental structure is quite similar to the human placenta.
      Here, we describe our studies that explored the pregnant guinea pig as a model to
      study in utero Group B Streptococci (GBS) infections. We observed that
      intrauterine inoculation of wild type GBS in pregnant guinea pigs resulted in
      bacterial invasion and dissemination to the placenta, amniotic fluid and fetal
      organs. Also, hyperhemolytic GBS such as those lacking the hemolysin repressor
      CovR/S showed increased dissemination into the amniotic fluid and fetal organs
      such as the fetal lung and brain. These results are similar to those observed in
      mouse and non-human primate models of in utero infection, and support use of the
      guinea pig as a model for studying GBS infections in pregnancy.

PMID- 29034377
TI  - Breaking BAD: A Data Serving Vision for Big Active Data.
AB  - Virtually all of today's Big Data systems are passive in nature. Here we describe
      a project to shift Big Data platforms from passive to active. We detail a vision
      for a scalable system that can continuously and reliably capture Big Data to
      enable timely and automatic delivery of new information to a large pool of
      interested users as well as supporting analyses of historical information. We are
      currently building a Big Active Data (BAD) system by extending an existing
      scalable open-source BDMS (AsterixDB) in this active direction. This first paper
      zooms in on the Data Serving piece of the BAD puzzle, including its key concepts
      and user model.

PMID- 29034378
TI  - Editorial: We can do more: The role of dentists extends beyond traditional
      dentistry.

PMID- 29034379
TI  - Medical malpractice: An introduction for the dental practitioner.
AB  - With the plethora of medical malpractice claims, health care providers are forced
      to deal not only with medical matters but also with legal issues. Thus,
      unfortunately, every time health care providers give a medical treatment, they
      should be aware of the legal implications of their act. Most medical malpractice
      cases will be resolved in civil law and will have financial implications, but in
      extreme cases (such as causing death by negligence) criminal procedure may also
      be conducted, meaning criminal sanctions (imprisonment or fine). This paper is
      intended to provide dental practitioners with an introduction to basic legal
      knowledge and concepts regarding medical malpractice law along with a short legal
      overview regarding the liability regime in different countries. The paper focuses
      on tort law and the meaning of "negligence," reviewing the main different
      liability regimes that exist and the legal elements that must be proven in each
      regime in order to receive compensation. In an era of increase in medical
      malpractice law suits, it is essential that physicians and dental professionals
      recognize the basic legal concepts of medical malpractice.

PMID- 29034381
TI  - The first anion-exchange membrane fuel cell to exceed 1 W cm-2 at 70  degrees C
      with a non-Pt-group (O2) cathode.
AB  - Anion-exchange membrane fuel cells face two challenges: performance and
      durability. Addressing the first, we demonstrate high performance with both O2
      and CO2-free air supplies, even when using a Ag/C cathode. This was enabled by
      the development of a radiation-grafted anion-exchange membrane that was less than
      30 MUm thick when hydrated.

PMID- 29034380
TI  - The immobilization of antibiotic-loaded polymeric coatings on osteoarticular Ti
      implants for the prevention of bone infections.
AB  - Implant-associated infections in orthopaedic surgeries are very critical as they
      may hinder bone healing, cause implant failure and even progress to
      osteomyelitis. Drug-eluting implants for local delivery of antibiotics at
      surgical sites are thought to be promising in preventing infections. Herein, the
      antibiotic vancomycin was encapsulated in a poly(ethylene glycol) (PEG)-based
      hydrogel film that was covalently bound to Ti implants and subsequently covered
      by a PEG-poly(lactic-co-caprolactone) (PEG-PLC) membrane. Additionally,
      crosslinked starch (CSt) was mixed with the hydrogel because its porous
      microstructure is able to inhibit hydrogel swelling and thus slow down drug
      release. The release behavior could be regulated by the drug loading and the
      coating thickness. The vancomycin-loaded Ti implants showed no initial burst
      release, offering a sustained drug release for nearly 3 weeks in vitro and more
      than 4 weeks in vivo. In a rabbit model of S. aureus infection, the implants with
      a 4 mg vancomycin loading significantly reduced the inflammatory reaction and
      exhibited a good antimicrobial capability. The immobilization of the antibiotic
      loaded polymeric coatings on orthopaedic implants can offer a sustainable drug
      release with no initial burst release and maintain an effective concentration for
      a longer time, so it is expected to be an effective strategy to treat and prevent
      local bone infections.

PMID- 29034382
TI  - Environmental photochemistry of dienogest: phototransformation to estrogenic
      products and increased environmental persistence via reversible photohydration.
AB  - Potent trienone and dienone steroid hormones undergo a coupled photohydration (in
      light)-thermal dehydration (in dark) cycle that ultimately increases their
      environmental persistence. Here, we studied the photolysis of dienogest, a
      dienone progestin prescribed as a next-generation oral contraceptive, and used
      high resolution mass spectrometry and both 1D and 2D nuclear magnetic resonance
      spectroscopy to identify its phototransformation products. Dienogest undergoes
      rapid direct photolysis (t1/2 ~ 1-10 min), forming complex photoproduct mixtures
      across the pH range examined (pH 2 to 7). Identified products include three
      photohydrates that account for ~80% of the converted mass at pH 7 and revert back
      to parent dienogest in the absence of light. Notably, we also identified two
      estrogenic compounds produced via the A-ring aromatization of dienogest, evidence
      for a photochemically-induced increase in estrogenic activity in product
      mixtures. These results imply that dienogest will undergo complete and facile
      photolytic transformation in sunlit surface water, yet exhibit greater
      environmental persistence than might be anticipated by inspection of kinetic
      rates. Photoproduct mixtures also include transformation products with different
      nuclear receptor binding capabilities than the parent compound dienogest. These
      outcomes reveal a dynamic fate and biological risk profile for dienogest that
      must also take into account the composition and endocrine activity of its
      transformation products. Collectively, this study further illustrates the need
      for more holistic regulatory, risk assessment, and monitoring approaches for high
      potency synthetic pharmaceuticals and their bioactive transformation products.

PMID- 29034383
TI  - Ca-Embedded C2N: an efficient adsorbent for CO2 capture.
AB  - Carbon dioxide as a greenhouse gas causes severe impacts on the environment,
      whereas it is also a necessary chemical feedstock that can be converted into
      carbon-based fuels via electrochemical reduction. To efficiently and reversibly
      capture CO2, it is important to find novel materials for a good balance between
      adsorption and desorption. In this study, we performed first-principles
      calculations and grand canonical Monte Carlo (GCMC) simulations, to
      systematically study metal-embedded carbon nitride (C2N) nanosheets for CO2
      capture. Our first-principles results indicated that Ca atoms can be uniformly
      trapped in the cavity center of C2N structure, while the transition metals (Sc,
      Ti, V, Cr, Mn, Fe, Co) are favorably embedded in the sites off the center of the
      cavity. The determined maximum number of CO2 molecules with strong physisorption
      showed that Ca-embedded C2N monolayer is the most promising CO2 adsorbent among
      all considered metal-embedded materials. Moreover, GCMC simulations revealed that
      at room temperature the gravimetric density for CO2 adsorbed on Ca-embedded C2N
      reached 50 wt% at 30 bar and 23 wt% at 1 bar, higher than other layered
      materials, thus providing a satisfactory system for the CO2 capture and
      utilization.

PMID- 29034384
TI  - Phase formation and stability of Ag-60 at%Cu alloy nanoparticles synthesized by
      chemical routes in aqueous media.
AB  - The present work reports the nature of the evolution of an array of nanoparticles
      during the synthesis of alloy nanoparticles of Ag-60 at%Cu by the co-reduction of
      metal salt precursors using NaBH4 in an aqueous medium. This was achieved by
      studying samples extracted at different intervals of time from the reaction bath.
      The microstructural characterization reveals that at the initial stage of
      synthesis, a single-phase solid solution of alloy nanoparticles of very small
      sizes was formed; however, as the reaction time increases, a network of chains of
      nanoparticles evolves containing particles rich in either Ag or Cu. Keeping the
      particles in the reaction bath for a longer time, the chemistry of the network
      changes further with the chain containing an Ag-rich core and Cu2O as the shell.
      In the present study, we tried to rationalize the evolution of the phases from
      the observed results.

PMID- 29034385
TI  - Multivariate characterization of salt and fat content, and the fatty acid profile
      of pastry and bakery products.
AB  - Bakery and pastry products are highly appreciated worldwide. Due to consumer
      demand, a wide diversity of this type of food is available all over the world.
      The aim of this study was to evaluate the content of salt, fat and fatty acids in
      the composition of 91 bakery and pastry products commercialised in Portugal.
      Moreover, a detailed comparison between commercial and supermarket brands of
      similar foods, as well as between foods with or without gluten was performed. The
      obtained results allowed us to conclude that most of the analysed foods have a
      high percentage of saturated fatty acids. Also, considerable amounts of salt were
      determined, while the trans fatty acid content in the analysed foods was in
      general low (<0.5%). Moreover, differences in the salt content higher than 6-fold
      between brands of the same type of foodstuff were observed, which should be
      considered at the moment of choice. This fact proves that it is possible to
      produce similar foods which are healthier with better nutritional quality. Since
      this type of food is highly appreciated by people of all ages, but mostly by
      children and young people, it is of utmost importance to implement strategies and
      establish goals, to improve their nutritional quality.

PMID- 29034386
TI  - Auxeticity enhancement due to size polydispersity in fcc crystals of hard-core
      repulsive Yukawa particles.
AB  - The Poisson's ratio of the fcc hard-core repulsive Yukawa crystals with size
      polydispersity was determined by Monte Carlo simulations in the isothermal
      isobaric ensemble. The effect of size polydispersity on the auxetic properties of
      Yukawa crystals has been studied. It has been found that an increase of particle
      size polydispersity causes a decrease of the Poisson's ratio in auxetic
      directions as well as appearance of a negative Poisson's ratio in formerly non
      auxetic directions. A measure of auxeticity was introduced to estimate
      quantitatively an enhancement of auxetic properties in polydisperse Yukawa
      crystals. The proposed measure of auxeticity can be applied to appraise the
      auxeticity of any studied system.

PMID- 29034387
TI  - Theoretical design and mechanistic study of the metal-free reduction of CO2 to
      CO.
AB  - A strategy for the reduction of CO2 to CO by or catalyzed by metal-free
      silylboranes has been proposed with the aid of density functional theory (DFT)
      computations. We showed that one oxygen atom of CO2 can be abstracted by
      silylboranes without catalysts or by diboranes in the presence of silylborane
      catalysts with surprisingly low free-energy barriers so that the reaction can be
      realized under mild experimental conditions. To achieve this, the reduction
      mechanism of CO2 by a hierarchy of silylboranes (R1)2BSi(R2)3 was systematically
      investigated. Several rules of thumb were obtained to guide the design of
      silylboranes with high activity toward CO2 reduction. After considering many
      factors, such as side reactions, the stability of the silylboranes, and the
      solvent effect, two silylboranes, (PFP)2BSi(CH2F)3 and Me2BSi(CH2F)3, suitable
      for the reduction of CO2 under mild experimental conditions were designed. The
      overall free-energy barriers for the reduction of CO2 by the two silylboranes are
      just 26.1-27.0 kcal mol-1 and 28.1-28.9 kcal mol-1, respectively, at 298.15 K in
      solution. We further showed that CO2 can be reduced to CO by diborane Me2BBMe2
      using Me2BSi(CH2F)3 as the catalyst. The overall free-energy barrier for this
      catalytic reaction is just 30.6-30.7 kcal mol-1 at 298.15 K in solution.

PMID- 29034388
TI  - Probing properties of molecule-based interface systems: general discussion and
      Discussion of the Concluding Remarks.

PMID- 29034389
TI  - High-performance supercapacitors of Cu-based porous coordination polymer
      nanowires and the derived porous CuO nanotubes.
AB  - Electrode materials for supercapacitors with one-dimensional porous
      nanostructures, such as nanowires and nanotubes, are very attractive for high
      efficiency storage of electrochemical energy. Herein, ultralong Cu-based porous
      coordination polymer nanowires (copper-l-aspartic acid) were used as the
      electrode material for supercapacitors, for the first time. The as-prepared
      material exhibits a high specific capacitance of 367 F g-1 at 0.6 A g-1 and
      excellent cycling stability (94% retention over 1000 cycles). Moreover, porous
      CuO nanotubes were successfully fabricated by the thermal decomposition of this
      nanowire precursor. The CuO nanotube exhibits good electrochemical performance
      with high rate capacity (77% retention at 12.5 A g-1) and long-term stability
      (96% retention over 1000 cycles). The strategy developed here for the synthesis
      of porous nanowires and nanotubes can be extended to the construction of other
      electrode materials for more efficient energy storage.

PMID- 29034390
TI  - Molecular assembly at surfaces: progress and challenges.
AB  - Molecules provide versatile building blocks, with a vast palette of
      functionalities and an ability to assemble via supramolecular and covalent
      bonding to generate remarkably diverse macromolecular systems. This is abundantly
      displayed by natural systems that have evolved on Earth, which exploit both
      supramolecular and covalent protocols to create the machinery of life.
      Importantly, these molecular assemblies deliver functions that are reproducible,
      adaptable, finessed and responsive. There is now a real need to translate complex
      molecular systems to surfaces and interfaces in order to engineer 21st century
      nanotechnology. 'Top-down' and 'bottom-up' approaches, and utilisation of
      supramolecular and covalent assembly, are currently being used to create a range
      of molecular architectures and functionalities at surfaces. In parallel, advanced
      tools developed for interrogating surfaces and interfaces have been deployed to
      capture the complexities of molecular behaviour at interfaces from the nanoscale
      to the macroscale, while advances in theoretical modelling are delivering
      insights into the balance of interactions that determine system behaviour. A few
      examples are provided here that outline molecular behaviour at surfaces, and the
      level of complexity that is inherent in such systems.

PMID- 29034391
TI  - Glycerol as a source of designer solvents: physicochemical properties of low
      melting mixtures containing glycerol ethers and ammonium salts.
AB  - In this work we report the preparation of mixtures of several alkyl glyceryl
      ethers, as hydrogen bond donor compounds, with two ammonium salts, choline
      chloride and N,N,N-triethyl-2,3-dihydroxypropan-1-aminium chloride. The stability
      of the mixtures at different molar ratios and temperatures has been evaluated in
      order to determine the formation of low melting mixtures. Liquid and stable
      mixtures have been characterized and their physico-chemical properties such as
      density, viscosity, refractive index, conductivity and surface tension have been
      measured in the temperature range of 293.15 K to 343.15 K. Comparison of the
      mixtures prepared herein with the ones containing glycerol and choline chloride
      evidences the possibility of tuning the physico-chemical properties by changing
      the substitution pattern in the hydrogen bond donor compound or in the ammonium
      salt, thus broadening the scope of application of these mixtures.

PMID- 29034392
TI  - New dimensions in salt-solvent mixtures: a 4th evolution of ionic liquids.
AB  - In the field of ionic liquids (ILs) it has long been of fundamental interest to
      examine the transition from salt-in-solvent behaviour to pure liquid-salt
      behaviour, in terms of structures and properties. At the same time, a variety of
      applications have beneficially employed IL-solvent mixtures as media that offer
      an optimal set of properties. Their properties in many cases can be other than as
      expected on the basis of simple mixing concepts. Instead, they can reflect the
      distinct structural and interaction changes that occur as the mixture passes
      through the various stages from pure coulombic medium, to "plasticised" coulombic
      medium, into a meso-region where distinct molecular and ionic domains can co
      exist. Such domains can persist to quite a high dilution into the salt-in-solvent
      regime and their presence manifests itself in a number of important synergistic
      interaction effects in diverse areas such as membrane transport and corrosion
      protection. Similarly, the use of ionic liquids in synthetic processes where
      there is a significant volume fraction of molecular species present can produce a
      variety of distinct and unexpected effects. The range of these salt-solvent
      mixtures is considerably broader than just those based on ionic liquids, since
      there is only minor value in the pure salt being a liquid at the outset. In other
      words, the extensive families of organic and metal salts become candidates for
      study and use. Our perspective then is of an evolution of ionic liquids into a
      broader field of fundamental phenomena and applications. This can draw on an even
      larger family of tuneable salts that exhibit an exciting combination of
      properties when mixed with molecular liquids.

PMID- 29034394
TI  - A calibrated UV-LED based light source for water purification and
      characterisation of photocatalysis.
AB  - Photocatalysis has a potential to become a cost effective industrial process for
      water cleaning. One of the most studied photocatalysts is titanium dioxide which,
      as a wide band gap semiconductor, requires ultraviolet (UV) light for its
      photoactivation. This is at the wavelengths where the efficiency of present-day
      light emitting diodes (LEDs) decreases rapidly, which presents a challenge in the
      use of UV-LEDs for commercially viable photocatalysis. There is also a need for
      accurate photocatalysis measurement of remediation rates of water-borne
      contaminants for determining optimum exposure doses in industrial applications.
      In response to these challenges, this paper describes a UV-LED based
      photocatalytic test reactor that provides a calibrated adjustable light source
      and pre-defined test conditions to remove as many sources of uncertainty in
      photocatalytic analysis as possible and thereby improve data reliability. The
      test reactor provides a selectable intensity of up to 1.9 kW m-2 at the
      photocatalyst surface. The comparability of the results is achieved through the
      use of pre-calibration and control electronics that minimize the largest sources
      of uncertainty; most notably variations in the intensity and directionality of
      the UV light emission of LEDs and in LED device heating.

PMID- 29034393
TI  - Centrifugal micropipette-tip with pressure signal readout for portable
      quantitative detection of myoglobin.
AB  - This paper describes a centrifugal micropipette-tip method for ELISA sample
      processing combined with a pressure meter for portable quantitative detection of
      acute myocardial infarction (AMI) biomarker myoglobin (Myo). The method enables
      sensitive and reliable quantification of Myo in 35 minutes. With the advantages
      of simplicity, speed, user friendliness, low cost, and small sample consumption,
      centrifugal micropipette-tip ELISA shows great potential for quantitative POC
      diagnostics for AMI.

PMID- 29034395
TI  - A platinum catalyst deposited on a zirconia support for the design of lithium
      oxygen batteries with enhanced cycling ability.
AB  - A platinum catalyst supported on zirconia is proposed as a cathode in lithium
      oxygen batteries. Experimental and theoretical studies show that zirconia
      suppresses the side-reactions of the intermediate (O2-) and the final product
      (Li2O2) by the stabilization of their reactivity. Thus, it is able to enhance the
      reversibility during charge/discharge in lithium-oxygen batteries.

PMID- 29034396
TI  - Defined pH-sensitive nanogels as gene delivery platform for siRNA mediated in
      vitro gene silencing.
AB  - In the present study, a pH sensitive nanogel platform for gene delivery was
      developed. The cationic nanogels based on dendritic polyglycerol (dPG) and low
      molecular weight polyethylenimine units were able to encapsulate siRNA during the
      manufacturing process. The thiol-Michael nanoprecipitation method, which operates
      under mild conditions and did not require any catalyst or surfactant, was used to
      develop tailor-made nanogels in the sub-100 nm range. The incorporation of pH
      sensitive benzacetal-bonds inside the nanogel network enables the controlled
      intracellular release of the cargo. The functionality to transport therapeutic
      biomolecules was tested by an in vitro GFP-siRNA transfection assay. Encapsulated
      siRNA could silence GFP expressing HeLa cells (up to 71% silencing in GFP).
      Furthermore, significantly reduced toxicity of the nanogel platform compared to
      the non-degradable PEI was observed. These properties realize a new carrier
      platform in the field of gene therapy.

PMID- 29034397
TI  - Electrically tunable tunneling rectification magnetoresistance in magnetic
      tunneling junctions with asymmetric barriers.
AB  - The development of multifunctional spintronic devices requires simultaneous
      control of multiple degrees of freedom of electrons, such as charge, spin and
      orbit, and especially a new physical functionality can be realized by combining
      two or more different physical mechanisms in one specific device. Here, we report
      the realization of novel tunneling rectification magnetoresistance (TRMR), where
      the charge-related rectification and spin-dependent tunneling magnetoresistance
      are integrated in Co/CoO-ZnO/Co magnetic tunneling junctions with asymmetric
      tunneling barriers. Moreover, by simultaneously applying direct current and
      alternating current to the devices, the TRMR has been remarkably tuned in the
      range from -300% to 2200% at low temperature. This proof-of-concept investigation
      provides an unexplored avenue towards electrical and magnetic control of charge
      and spin, which may apply to other heterojunctions to give rise to more
      fascinating emergent functionalities for future spintronics applications.

PMID- 29034398
TI  - Structural discontinuity induced surface second harmonic generation in single,
      thin zinc-blende GaAs nanowires.
AB  - We investigate optical second harmonic generation (SHG) from individual self
      catalyzed zinc-blende (ZB) GaAs nanowires (NWs), where the polarimetry strongly
      depends on the NW diameter. We report a direct observation on the SHG induced by
      surface nonlinear susceptibilities in a single, ultra-thin GaAs NW. By
      considering the contributions from both optical field and structural
      discontinuities in our theoretical model, we can well explain the optical SHG
      polarimetry from NWs with different diameters. We also show that the optical in
      coupling coefficient arising from the depolarization electromagnetic field can
      determine the polarization of the SHG. The results open perspectives for further
      geometry-based studies on the origin and control of SHG in small nanostructures.

PMID- 29034399
TI  - In situ growth of cobalt@cobalt-borate core-shell nanosheets as highly-efficient
      electrocatalysts for oxygen evolution reaction in alkaline/neutral medium.
AB  - Development of efficient non-noble metal electrocatalysts for oxygen evolution
      reaction (OER) is still a crucial issue for renewable energy technologies.
      Herein, we report a core-shell-like catalyst of amorphous cobalt borate
      nanosheets grown on metallic cobalt deposited on Ti-mesh (Co@Co-Bi/Ti) by an in
      situ conversion strategy. Benefiting from the high activity, large surface area
      of Co-Bi nanosheets, outstanding electronic conductivity of metallic Co and the
      3D structure inherited from Ti-mesh substrate, Co@Co-Bi/Ti shows high OER
      activity with a relatively small overpotential of 329 mV to obtain a current
      density of 10 mA cm-2, a low Tafel slope of 46 mV dec-1 and an accessible large
      current density of 500 mA cm-2 in alkaline solution. Besides, Co@Co-Bi/Ti
      exhibits good performance in a near-neutral medium. This study provides an
      effective pathway to improve the cobalt metal based materials.

PMID- 29034400
TI  - Preparing macromolecular systems on surfaces: general discussion.

PMID- 29034401
TI  - Metal fluoride nanotubes featuring square-planar building blocks in a high
      pressure polymorph of AgF2.
AB  - At a pressure of ca. 15 GPa, AgF2 transforms to an unprecedented orthorhombic
      polymorph featuring an array of tubular subunits which are built of corner
      sharing [AgF4] squares. This seems to be the first type of a metal fluoride
      nanowire and also the only one showing rigid square planar rather than common
      hexagonal or octahedral moieties.

PMID- 29034402
TI  - Nanoprocess and nanoscale surface functionalization on cathode materials for
      advanced lithium-ion batteries.
AB  - Nanotechnology-driven development of cathode materials is an essential part to
      revolutionize the evolution of the next generation lithium ion batteries. With
      the progress of nanoprocess and nanoscale surface modification investigations on
      cathode materials in recent years, the advanced battery technology future seems
      very promising - Thanks to nanotechnology. In this review, an overview of
      promising nanoscale surface deposition methods and their significance in surface
      functionalization on cathodes is extensively summarized. Surface modified
      cathodes are provided with a protective layer to overcome the electrochemical
      performance limitations related to side reactions with electrolytes, reduce self
      discharge reactions, improve thermal and structural stability, and further
      enhance the overall battery performance. The review addresses the importance of
      nanoscale surface modification on battery cathodes and concludes with a
      comparison of the different nanoprocess techniques discussed to provide a
      direction in the race to build advanced lithium-ion batteries.

PMID- 29034403
TI  - Customised spatiotemporal temperature gradients created by a liquid metal enabled
      vortex generator.
AB  - Generating customised temperature gradients in miniaturised flow-free liquid
      chambers is challenging due to the dominance of diffusion. Inducing internal
      flows in the form of vortices is an effective strategy for overcoming the
      limitations of diffusion in such environments. Vortices can be produced by
      applying pressure, temperature and electric potential gradients via miniaturised
      actuators. However, the difficulties associated with the fabrication,
      integration, maintenance and operation of such actuators hinder their utility.
      Here, we utilise liquid metal enabled pumps to induce vortices inside a
      miniaturised liquid chamber. The configuration and rotational velocity of these
      vortices can be controlled by tuning the polarity and frequency of the energising
      electrical signal. This allows creation of customised spatial temperature
      gradients inside the chamber. The absence of conventional moving elements in the
      pumps facilitates the rapid reconfiguration of vortices. This enables quick
      transition from one temperature profile to another, and creates customised
      spatiotemporal temperature gradients. This allows temperature oscillation from 35
      to 62  degrees C at the hot spot, and from 25 to 27  degrees C at the centre of
      the vortex within 15 seconds. Our liquid metal enabled vortex generator can be
      fabricated, integrated and operated easily, and offers opportunities for studying
      thermo-responsive materials and biological samples.

PMID- 29034404
TI  - Quality control and gap-filling of PM10 daily mean concentrations with the best
      linear unbiased estimator.
AB  - According to the European Directive 2008/50/CE, the air quality assessment
      consists in the measurement of the concentration fields, and the evaluation of
      the mean, number of exceedances, etc. of some chemical species dangerous to human
      health. The measurements provided by an air quality ground-based monitoring
      network are the main information source but the availability of these data is
      often limited by several technical and operational problems. In this paper, the
      best linear unbiased estimator (BLUE) is proposed to validate the pollutant
      concentration values and to fill the gaps in the measurement of time series
      collected by a monitoring network. The BLUE algorithm is tested using the daily
      mean concentrations of particulate matter having aerodynamic diameter less than
      10 MU (PM10 concentrations) measured by the air quality monitoring sensors
      operating in the Lazio Region in Italy. The comparison between the estimated and
      measured data evidences an error comparable with the measurement uncertainty. Due
      to its simplicity and reliability, the BLUE will be used in the routine quality
      test procedures of the Lazio air quality monitoring network measurements.

PMID- 29034406
TI  - Correction to: Phase II study of bi-weekly temozolomide plus bevacizumab for
      adult patients with recurrent glioblastoma.

PMID- 29034405
TI  - Immunohistochemical and serological characterization of membranous nephropathy in
      children and adolescents.
AB  - BACKGROUND: Membranous nephropathy (MN) is a common cause of nephrotic syndrome
      in adults, but is less frequent in children. Antibodies against four antigens
      leading to MN have been described in children: phospholipase A2 receptor 1
      (PLA2R1), thrombospondin type-1 domain-containing 7A (THSD7A), neutral
      endopeptidase (NEP), and cationic bovine serum albumin (BSA). METHODS: Twelve
      children with MN were included in this study. Sera of all patients were analyzed
      for antibodies against PLA2R1, THSD7A, NEP, and BSA. All sera were also analyzed
      using Western blot with human glomerular extracts (HGE) under non reducing
      conditions. In 5 cases renal biopsies were analyzed for PLA2R1, THSD7A, NEP, BSA,
      and all IgG subclasses. RESULTS: Six patients were PLA2R1-antibody-positive,
      whereas THSD7A, NEP, and BSA antibodies were not found in any of our 12 patients.
      All sera were analyzed by Western blot using human glomerular extracts; however,
      no further potential antigens were found. Five kidney biopsies from 2 PLA2R1
      antibody-positive and 3 PLA2R1-antibody-negative patients were available for
      additional analyses, confirming the diagnosis of PLA2R1-associated MN in 2 cases,
      whereas none of the biopsies revealed enhanced staining for THSD7A, NEP or BSA.
      IgG2 and IgG4 stainings were positive in both patients with PLA2R1-associated MN
      and negative in the other biopsies. During follow-up (median 24 months), 4
      children with PLA2R1-associated MN went into remission, preceded by decline of
      PLA2R1 antibodies. Five of the 6 PLA2R1-antibody-negative children went into
      remission. CONCLUSIONS: In children with MN, PLA2R1-associated MN appears to be
      common, whereas MN associated with THSD7A, NEP or BSA was not encountered. PLA2R1
      antibody levels are closely associated with disease activity, whereas PLA2R1
      antibody-negative patients often have a good prognosis. However, the
      pathophysiology of MN in a considerable number of children remains unclear.

PMID- 29034407
TI  - Novel Mahalanobis-based feature selection improves one-class classification of
      early hepatocellular carcinoma.
AB  - Detection of early hepatocellular carcinoma (HCC) is responsible for increasing
      survival rates in up to 40%. One-class classifiers can be used for modeling early
      HCC in multidetector computed tomography (MDCT), but demand the specific
      knowledge pertaining to the set of features that best describes the target class.
      Although the literature outlines several features for characterizing liver
      lesions, it is unclear which is most relevant for describing early HCC. In this
      paper, we introduce an unconstrained GA feature selection algorithm based on a
      multi-objective Mahalanobis fitness function to improve the classification
      performance for early HCC. We compared our approach to a constrained Mahalanobis
      function and two other unconstrained functions using Welch's t-test and Gaussian
      Data Descriptors. The performance of each fitness function was evaluated by cross
      validating a one-class SVM. The results show that the proposed multi-objective
      Mahalanobis fitness function is capable of significantly reducing data
      dimensionality (96.4%) and improving one-class classification of early HCC (0.84
      AUC). Furthermore, the results provide strong evidence that intensity features
      extracted at the arterial to portal and arterial to equilibrium phases are
      important for classifying early HCC.

PMID- 29034408
TI  - Occurrence of organochlorine pesticides in a tropical lake basin.
AB  - This study investigates the presence and distribution of organochlorine
      pesticides in streams and the lake in the Sembrong Lake Basin in Malaysia. The
      catchment of Sembrong Lake has been converted to agricultural areas over the past
      30 years, with oil palm plantations and modern agricultural farming being the
      main land use. Surface water samples were collected from eight sites comprising
      the stream and lake and analysed for 19 organochlorine pesticides (OCPs). In situ
      measurement of temperature, dissolved oxygen, pH and conductivity were also
      undertaken at each site. Aldrin, endrin, delta-BHC, 4,4-DDT, methoxychlor and
      endosulfan were the main OCPs detected in the lake basin. The total OCP
      concentration ranged between 5.42 and 349.2 ng/L. The most frequently detected
      OCPs were delta-BHC, heptachlor and aldrin. The maximum values detected were
      23.0, 43.2 and 50.4 ng/L respectively. The highest concentration of OCPs was
      attributed to 4,4-DDT, but such high residue was rare and only detected once.
      Other OCP residues were low. Significant differences in the mean values were
      observed between lake and stream for dichlorodiphenyldichloroethylene (DDE) and
      alpha-endosulfan concentration (p < 0.05). The highest endosulfan, endrin and
      methoxychlor residues were found in lake sites, while the highest 4,4,-DDT
      residues were observed for the river sites. Temporal variation of OCP residues
      was observed for heptachlor and beta-endosulfan. The highest concentrations of
      pesticide residues were found in October. DDX and alpha/gamma ratios indicate
      possible fresh inputs of the OCP pesticide in the basin.

PMID- 29034409
TI  - Multi-criteria analysis for municipal solid waste management in a Brazilian
      metropolitan area.
AB  - The decision-making process involved in municipal solid waste management (MSWM)
      must consider more than just financial aspects, which makes it a difficult task
      in developing countries. The Recife Metropolitan Region (RMR) in the Northeast of
      Brazil faces a MSWM problem that has been ongoing since the 1970s, with no common
      solution. In order to direct short-term solutions, three MSWM alternatives were
      outlined for the RMR, considering the current and future situations, the time and
      cost involved and social/environmental criteria. A multi-criteria approach, based
      on the Preference Ranking Organization Method for Enrichment Evaluations
      (PROMETHEE), was proposed to rank these alternatives. The alternative that
      included two private landfill sites and seven transfer, sorting and composting
      stations was confirmed as the most suitable and stable option for short-term
      MSWM, considering the two scenarios for the criteria weights. Sensitivity
      analysis was also performed to support the robustness of the results. The
      implementation of separate collections would minimize the amount of waste buried,
      while maximizing the useful life of landfill sites and increasing the timeframe
      of the alternative. Overall, the multi-criteria analysis was helpful and accurate
      during the alternative selection process, considering the similarities and
      restrictions of each option, which can lead to difficulties during the decision
      making process.

PMID- 29034410
TI  - Caste matters: perceived discrimination among women in rural India.
AB  - The aim of this study is to examine the relationship of caste and class with
      perceived discrimination among pregnant women from rural western India. A cross
      sectional survey was administered to 170 pregnant women in rural Gujarat, India,
      who were enrolled in a longitudinal cohort study. The Everyday Discrimination
      Scale and the Experiences of Discrimination questionnaires were used to assess
      perceived discrimination and response to discrimination. Based on self-report
      caste, women were classified into three categories with increasing historical
      disadvantage: General, Other Backward Castes (OBC), and Scheduled Caste or Tribes
      (SC/ST). Socioeconomic class was determined using the standardized Kuppuswamy
      scale. Regression models for count and binomial data were used to examine
      association of caste and class with experience of discrimination and response to
      discrimination. Sixty-eight percent of women experienced discrimination. After
      adjusting for confounders, there was a consistent trend and association of
      discrimination with caste but not class. In comparison to General Caste, lower
      caste (OBC, SC/ST) women were more likely to (1) experience discrimination (OBC
      OR: 2.2, SC/ST: 4.1; p trend: 0.01); (2) have a greater perceived discrimination
      score (OBC IRR: 1.3, SC/ST: 1.5; p trend: 0.07); (3) accept discrimination (OBC
      OR: 6.4, SC/ST: 7.6; p trend: < 0.01); and (4) keep to herself about
      discrimination (OBC OR: 2.7, SC/ST: 3.6; p trend: 0.04). The differential
      experience of discrimination by lower caste pregnant women in comparison to upper
      caste pregnant women and their response to such experiences highlight the
      importance of studying discrimination to understand the root causes of existing
      caste-based disparities.

PMID- 29034413
TI  - Abstracts Laser Florence 2017.

PMID- 29034411
TI  - Impact of corneal donor lens status on two-year course and outcome of Descemet
      membrane endothelial keratoplasty (DMEK).
AB  - PURPOSE: Our purpose was to investigate the impact of lens status of corneal
      donors on the two-year course and clinical outcome of Descemet membrane
      endothelial keratoplasty (DMEK). METHODS: In 181 DMEK surgeries, 136 phakic and
      45 pseudophakic donor corneas were grafted. In this retrospective audit we
      compared the lens status of corneal donors regarding the outcome measures best
      spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), and
      endothelial cell density (ECD) at 1, 3, 6, 12, and 24 months, as well as intra-
      and postoperative complication rates and graft detachment rates requiring re
      bubbling. RESULTS: Comparing the use of phakic and pseudophakic donor tissue in
      DMEK surgery, BSCVA results revealed no significant differences during the two
      year course (p >= 0.087). CCT showed significantly lower values at 1 month (553.8
      +/- 56 vs. 625.2 +/- 119 MUm; p < 0.001) and 6 months follow-up (530.6 +/- 49.9
      vs. 557.3 +/- 47 MUm; p = 0.026) for phakic donor tissue recipients, but were
      comparable later (p >= 0.173). ECD values were statistically higher 6 (1915 +/-
      390 vs. 1565 +/- 420 cells/mm2; p < 0.001) and 24 months postoperatively (1772 +/
      384 vs. 1375 +/- 377 cells/mm2; p = 0.030) in phakic donor tissue recipients.
      Mixed regression analyses demonstrated a significant association between ECD
      results and donor lens status (p = 0.029) and donor ECD (p = 0.028), but donor
      age did not show significant influence (p = 0.241). CONCLUSION: ECD is higher in
      phakic corneal donors and appears to remain at a higher level during the course
      resulting in initially faster reduction of corneal edema compared to pseudophakic
      DMEK grafts. Nevertheless, pseudophakic transplants with high ECD seem to produce
      comparable functional results in recipients after a two year course.

PMID- 29034412
TI  - Memory effect and anisotropy of particle arrangements in granular paste.
AB  - It is known that pastes of fine powder, for example those of clay, retain memory
      of shaking applied early in a drying process. This memory results in the
      appearance of anisotropic patterns of desiccation cracks after drying. In this
      work, we find a similar behavior in pastes consisting of large granular
      particles, specifically cornstarch and Lycopodium spores. Because of the large
      particle size, we were able to observe particle arrangements in Lycopodium paste
      with micro-focus X-ray computerized tomography ( MU CT). We prepared pastes
      consisting of Lycopodium particles and water. Agar was added to the paste in
      order to allow for solidification during a drying process. In these samples, we
      found statistical anisotropy induced by shaking applied early in the drying
      process. This anisotropy possesses a feature that was predicted on the basis of
      results obtained in previous experimental and theoretical studies.

PMID- 29034414
TI  - Occurrence and zoonotic potential of endoparasites in cats of Cyprus and a new
      distribution area for Troglostrongylus brevior.
AB  - The present study investigated for the first time the occurrence of pulmonary and
      intestinal parasites of cats in Cyprus. Cats from five districts of Cyprus
      (Lefkosia, Lemesos, Larnaka, Pafos and Ammochostos) were examined by classical
      parasitological methods and the identity of lungworm larvae, whenever present,
      was confirmed by PCR-coupled sequencing. A total of 185 cats, 48 living
      exclusively indoors and 137 with outdoor access, were included in the study.
      Parasites were found in 66 (35.7%) of the examined cats, i.e. Toxocara cati
      (12%), Cystoisospora rivolta (12%), Joyeuxiella/Diplopylidium spp. (7%), Giardia
      spp. (6.5%), Troglostrongylus brevior (5%), Cystoisospora felis (2.5%),
      Aelurostrongylus abstrusus (2%), Taenia spp. (0.5%) and Dipylidium caninum
      (0.5%). Mixed infections were recorded in 18 cats. Cats that lived exclusively
      indoors or had received an antiparasitic treatment in the last 6 months were less
      likely to be infected (p < 0.05). Moreover, cats younger than 1 year old were
      more likely to shed first-stage larvae of T. brevior (p = 0.04). The present
      study shows that cats in Cyprus are infected at a high percentage by a variety of
      parasites that potentially affect their health and also, in some cases (i.e. T.
      cati, D. caninum, Giardia spp.), may have an impact on human health. Moreover, it
      was revealed that T. brevior, a lungworm of emerging significance, is present on
      the island, rendering Cyprus the easternmost distribution border of this parasite
      in Europe to date.

PMID- 29034415
TI  - A diabetic ketoacidosis in a context of hyperglycemia addiction.
AB  - We herein present a case of a 20-year-old woman who suffered from type I diabetes
      mellitus and died from a diabetic ketoacidosis in a context of addiction to
      hyperglycemia. Diabetic ketoacidosis is a lethal complication of insulin
      dependent diabetes mellitus, which can result from insulin therapy stoppage. This
      can occur voluntarily with suicidal intent or involuntarily due to treatment
      inaccessibility, forgotten injections, or material deficiency. A new possibility
      is investigated in our case study: hyperglycemia addiction. The patient was
      treated by insulin glargine and insulin aspartate. She regularly stopped insulin
      glargine injections seeking the asthenia sensation produced by hyperglycemia,
      keeping the insulin aspartate injections to treat the disabling symptom related
      to hyperketonemia.

PMID- 29034416
TI  - Time since death in a case of simultaneous demise due to a single gunshot: an
      issue concerning the use of Henssge's nomogram.
AB  - We report a case of a double homicide in which the victims, a man and his
      daughter, were simultaneously killed by a single gunshot. The temperature-based
      nomogram method for estimation of the time since death was used to ascertain the
      reliability of the method in a case of simultaneous demise, where the exact time
      of death was obtained from the analysis of security cameras.In the case
      presented, the victims differed for a great number of parameters (e.g.,
      atmospheric conditions, thermal insulation of lower trunk, and, above all, body
      weight), except for the time of death, that was simultaneous. The correct
      application of the method permitted us to conclude that the estimated time since
      death was fully consistent with the circumstantial data obtained by the analysis
      of security cameras.No previous papers reporting the use of the nomogram method
      in a case of ascertained simultaneously death exists in literature; issues
      concerning the use of the nomogram method have been presented as well.

PMID- 29034417
TI  - Age estimation of Chinese children based on second molar maturity.
AB  - In forensic medicine and many other fields, age estimation by the use of teeth is
      of great importance for the purpose of individual identification. In the past,
      however, age estimation based on the second molar mineralization was scarcely
      performed. In this study, a total of 1657 panoramic radiographs taken from 834
      males and 823 females of northern Chinese origin in the age bracket 5 to 25 years
      were assessed. The mineralization status of the second molars was determined
      using the classification described by Demirjian et al. Results showed that the
      left and right, as well as maxillary and mandibular second molars were generally
      at similar stages of mineralization. The maxillary left second molars (27) at
      stage D, mandibular left second molars (37) at stages C, D, F, and G, and
      mandibular right second molars (47) at stages D, F, and G showed a significantly
      lower average age in female subjects than in male subjects. In males, fully
      developed second molars first appeared with 12 years of age; in females, stage H
      occurred with 11 years at the earliest. One male individual and one female
      individual with second molars showing stage G were 23 years old. It was concluded
      that second molars showing stage H do not exclude an age under 14 years and that
      second molars showing stage G do not exclude an age above 18 years.

PMID- 29034418
TI  - Botanical Nomenclature in Pharmacovigilance and a Recommendation for
      Standardisation.
AB  - Nomenclature of plants in pharmacology can be presented by pharmaceutical names
      or scientific names in the form of Linnaean binomials. In this paper, positive
      and negative aspects of both systems are discussed in the context of the
      scientific nomenclatural framework and the systems' practical applicability. The
      Uppsala Monitoring Centre (UMC) runs the WHO Programme for International Drug
      Monitoring and is responsible for the WHO Adverse Drug Reaction (ADR) database
      that currently contains 3.6 million records. In order for the UMC to monitor
      pharmacovigilance through ADRs to herbal medicine products the following
      nomenclatural criteria are important: (i) the name should indicate only one
      species of plant; (ii) the source for this name must be authoritative; (iii) the
      name should indicate which part of the plant is used. Based on these criteria,
      the UMC investigated four options: (i) adopt main names used in recognised (inter
      ) national pharmacopoeias or authoritative publications; (ii) adopt option 1, but
      cite the publication for all names in abbreviated form; (iii) three-part
      pharmaceutical names consisting of Latinised part name plus Latinised genus name,
      plus Latinised specific epithet; (iv) scientific binomial names, optionally with
      author and plant part used. The UMC has chosen the latter option and will at its
      adoption utilise the scientific botanical nomenclature as defined by the
      International Code of Botanical Nomenclature. This decision satisfies all
      criteria set by the UMC and renders the necessity of creating a new system or
      upgrading an old inconsistent system obsolete. The UMC has also issued an
      extensive synonymy checklist of vernacular, pharmaceutical and scientific names
      for the herbals in the WHO ADR database. We strongly recommend the adoption of
      scientific names to denote plant ingredients in medicine.

PMID- 29034419
TI  - Esophagitis unrelated to reflux disease: current status and emerging diagnostic
      challenges.
AB  - There has been much progress in our understanding of esophageal inflammatory
      disorders in the past few years. This is particularly true about esophageal
      eosinophilia and PPI responsiveness, lymphocytic esophagitis and motility
      disorders, and short-term risk of neoplasia in esophageal leukoplakia. The
      current review will summarize esophageal injury patterns that primarily occur due
      to non-reflux causes, with a focus on usual pitfalls in biopsy diagnosis and
      recent advances in our knowledge of the more common forms of esophagitis.

PMID- 29034420
TI  - Prevalence of dental agenesis in a sample of Italian orthodontic patients: an
      epidemiological study.
AB  - BACKGROUND: The congenital absence of one or more teeth is a dental anomaly that
      frequently occurs in the world's population with a wide variability of
      distribution. The aim of this study is to assess the current prevalence of dental
      agenesis in the permanent dentition (excluding third molars) using a sample of
      Italian orthodontic patients. METHODS: Panoramic radiographs of 4006 Caucasian
      children between 9 and 16 years of age (1865 males and 2141 females) performed
      over a 5-year period (from 2010 to 2015) were carefully examined to identify
      congenital missing teeth. A chi-square test was used to determine the difference
      in the prevalence of hypodontia between genders and between arches. RESULTS: The
      prevalence of dental agenesis was 9% (9.1% for females and 8.7% for males). The
      most common congenitally missing teeth were the mandibular second premolars (20.3
      and 18.1%) followed by the upper lateral incisors (17.8 and 17.7%) and the
      maxillary second premolars (7.4 and 6.3%). The absence of one tooth to five teeth
      was observed in 344 patients (8.6%), while 15 patients showed from six to nine
      missing teeth (0.4%). The analysis showed 363 cases of agenesis in the upper arch
      (0.64%) and 339 in the lower arch (0.60%). Unilateral (4.6%) and bilateral (4.4%)
      agenesis demonstrated a similar frequency. The most common bilateral missing
      teeth were the mandibular second premolars (1.9%) and the maxillary lateral
      incisors (1.6%). CONCLUSIONS: The results of this study observed a higher
      prevalence of hypodontia compared to previous studies conducted on the Italian
      population. Thus, a detailed and careful radiographic examination was important
      in diagnosing one or more missing teeth. This could help plan the best possible
      treatments, both esthetically and functionally, for these patients.

PMID- 29034422
TI  - A bibliometric analysis of research on haze during 2000-2016.
AB  - As one of the bibliometric analysis tools, CiteSpace software was applied to
      quantitatively and visually evaluate global scientific documents of research on
      haze from 2000 to 2016. Five thousand six hundred six documents from the Science
      Citation Index Expanded (SCI-Expanded) and Social Science Citation Index (SSCI)
      of the Web of Science database were statistically analyzed and examined. The
      distributions on authorship, countries/territories, institutes, and keywords were
      generated. The amount of publications has increased nearly for the past 17 years.
      The most productive author was Li J. with 46 articles. The publications on haze
      research were primarily originated from the USA, China, Germany, and France. By
      synthetically analyzing the keywords, the dominant hot spots of haze research
      could be concluded as "aerosol," "atmosphere," "particle," "PM2.5,"and "air
      quality."

PMID- 29034421
TI  - Hippocampal Deformations and Entorhinal Cortex Atrophy as an Anatomical Signature
      of Long-Term Cognitive Impairment: from the MCAO Rat Model to the Stroke Patient.
AB  - Stroke patients have an elevated risk of developing long-term cognitive disorders
      or dementia. The latter is often associated with atrophy of the medial temporal
      lobe. However, it is not clear whether hippocampal and entorhinal cortex atrophy
      is the sole predictor of long-term post-stroke dementia. We hypothesized that
      hippocampal deformation (rather than atrophy) is a predictive marker of long-term
      post-stroke dementia on a rat model and tested this hypothesis in a prospective
      cohort of stroke patients.Male Wistar rats were subjected to transient middle
      cerebral artery occlusion and assessed 6 months later. Ninety initially dementia
      free patients having suffered a first-ever ischemic stroke were prospectively
      included in a clinical study. In the rat model, significant impairments in
      hippocampus-dependent memories were observed. MRI studies did not reveal
      significant atrophy of the hippocampus volume, but significant deformations were
      indeed observed-particularly on the ipsilateral side. There, the neuronal surface
      area was significantly lower in ischemic rats and was associated with a lower
      tissue density and a markedly thinner entorhinal cortex. At 6 months post-stroke,
      49 of the 90 patients displayed cognitive impairment (males 55.10%). Shape
      analysis revealed marked deformations of their left hippocampus, a significantly
      lower entorhinal cortex surface area, and a wider rhinal sulcus but no
      hippocampal atrophy. Hence, hippocampal deformations and entorhinal cortex
      atrophy were associated with long-term impaired cognitive abilities in a stroke
      rat model and in stroke patients. When combined with existing biomarkers, these
      markers might constitute sensitive new tools for the early prediction of post
      stroke dementia.

PMID- 29034423
TI  - Effect and mechanism of microwave-activated ultraviolet-advanced oxidation
      technology for adsorbent regeneration.
AB  - To decrease the secondary pollution of volatile organic compounds (VOCs) during
      adsorbent regeneration by microwave, electrodeless lamp was added in the
      microwave field to oxidize VOCs in the gas phase. Ultraviolet has a significant
      improvement on mineralization of VOCs generated from adsorbate during adsorbent
      regeneration. However, the mechanism and main influence factors on the
      degradation of VOCs are not clear. The effect of microwave power, regeneration
      time, airflow rate, and humidity content on the mineralization of adsorbed
      tetracycline during adsorbent regeneration was studied. Ozone concentration and
      ultraviolet irradiation intensity were also measured to analyze the mechanism of
      the microwave-ultraviolet adsorbent regeneration method. Although the
      electrodeless lamp adsorbed microwave and competed with the regenerated
      adsorbent, the mineralization percentage of tetracycline increased about 10% with
      the presence of electrodeless lamp at the same microwave power supply. Besides,
      humidity content also takes an important role on enhancing the mineralization of
      tetracycline. The mineralization of tetracycline in the microwave-ultraviolet
      field consists of three major parts: pyrolysis, ozone oxidation, and free radical
      oxidation. More than 50% adsorbed tetracycline can be oxidized into H2O and CO2
      during regeneration in 5 min. These results support the potential use of
      electrodeless lamp to treat VOCs in the gas phase to decrease the risk of
      secondary pollution during adsorbent regeneration.

PMID- 29034424
TI  - Interaction mechanisms between polycyclic aromatic hydrocarbons (PAHs) and
      organic soil washing agents.
AB  - Understanding interaction mechanisms between polycyclic aromatic hydrocarbons
      (PAHs) and soil-washing agents can help in choosing efficient agents which are
      able to desorb and solubilize PAHs. This study investigated interaction
      mechanisms between pyrene and four washing agents including: two dissolved
      organic matters (DOM) F-DOM and CRC-DOM, and two commercial bio-based surfactants
      BBE-1000 and Supersolv using fluorescence spectroscopy combined with multivariate
      curve resolution alternating regression (MCR-AR). The efficiencies of these
      washing agents in removing PAHs from the soil were tested in a soil washing
      experiment. Pyrene showed pi-pi interactions with F-DOM and no interaction with
      CRC-DOM. This could be attributed to the more aromatic structures in F-DOM
      compared to CRC-DOM. The two DOMs were inefficient in soil washing which might be
      attributed to the relatively weak effect of pi-pi interactions in releasing PAHs
      from the soil. Interaction mechanisms between pyrene and the bio-based
      surfactants were elucidated with MCR-AR, which resolved three spectroscopically
      active species from pyrene emission spectra as a function of pyrene and bio-based
      surfactants concentrations. These species resembled pyrene emission in a polar
      and nonpolar microenvironment, respectively and of an excimer. Concentration
      profiles retrieved by the model for the three species showed that, below the
      critical micelle concentration (CMC), Supersolv created more nonpolar
      interactions with pyrene compared to BBE-1000. In soil washing, Supersolv showed
      the highest efficiency in extracting PAHs from the soil. This highlighted the
      importance of nonpolar interactions in desorbing PAHs from soils, which could
      then be solubilized in micelles. This study demonstrated the potential of
      fluorescence spectroscopy combined with the MCR-AR model for selecting efficient
      soil-washing agents.

PMID- 29034425
TI  - Kinetics of imidazolium-based ionic liquids degradation in aqueous solution by
      Fenton oxidation.
AB  - In the last few years, several works dealing with Fenton oxidation of ionic
      liquids (ILs) have proved the capability of this technology for their
      degradation, achieving complete ILs removal and non-toxic effluents.
      Nevertheless, very little is known about the kinetics of this process, crucial
      for its potential application. In this work, the effect of several operating
      conditions, including reaction temperature (50-90  degrees C), catalyst load (10
      50 mg L-1 Fe3+), initial IL concentration (100-2000 mg L-1), and hydrogen
      peroxide dose (10-200% of the stoichiometric amount for the complete IL
      mineralization) on 1-butyl-3-methylimidazolium chloride ([C4mim]Cl) oxidation has
      been investigated. Under the optimum operating conditions (T = 90  degrees C;
      [Fe3+]0 = 50 mg L-1; [H2O2]0 = 100% of the stoichiometric amount), the complete
      removal of [C4mim]Cl (1000 mg L-1) was achieved at 1.5-min reaction time. From
      the experimental results, a potential kinetic model capable to describe the
      removal of imidazolium-based ILs by Fenton oxidation has been developed. By
      fitting the proposed model to the experimental data, the orders of the reaction
      with respect to IL initial concentration, Fe3+ amount and H2O2 dose were found to
      be close to 1, with an apparent activation energy of 43.3 kJ mol-1. The model
      resulted in a reasonable fit within the wide range of operating conditions tested
      in this work.

PMID- 29034426
TI  - Macrophytes as potential biomonitors in peri-urban wetlands of the Middle Parana
      River (Argentina).
AB  - The aims of this study were to measure the concentrations of nutrients and
      pollutants in peri-urban wetlands, to analyze the plant morphology of the most
      representative macrophyte species, and to determine their potential use as
      biomonitors. Four wetlands in the Middle Parana River floodplain evidencing
      contamination or anthropogenic impact were studied. The studied species were
      Typha domingensis Pers., Eichhornia crassipes (Mart.) Solms., Alternanthera
      philoxeroides (Mart.) Griseb., and Pistia stratiotes L. Besides, the same plant
      species from an uncontaminated wetland considered as control were studied. A.
      philoxeroides showed the highest total phosphorus (TP) concentration in leaves
      throughout the study, while the other species showed a higher TP concentration in
      roots than in leaves. Since metal concentration in A. philoxeroides tissues was
      always higher than in sediment, further studies focused on its phytoremediation
      capacity should be carried out. T. domingensis exhibited the highest Zn
      concentrations in roots followed by Pb, and E. crassipes presented the highest
      values of Pb concentrations in roots. The aerial part height of the plants from
      peri-urban wetlands was significantly higher than that of the plants from the
      control, while the root length was significantly lower. The root length of P.
      stratiotes showed a negative correlation with soluble reactive phosphorus (SRP)
      concentration in water. All the root anatomical parameters of T. domingensis and
      E. crassipes showed a positive correlation with nitrate and ammonium
      concentrations in water. The studied macrophytes evidenced a high tolerance,
      enabling them to grow and survive in peri-urban wetlands that receive pollution
      from different sources. The use of aquatic and wetland plants as contaminant
      bioindicators and bioaccumulators in the Middle Parana River floodplain is
      completely feasible.

PMID- 29034428
TI  - Heterogeneous electro-Fenton catalyst for 1-butylpyridinium chloride degradation.
AB  - The application of the electro-Fenton process for organic compound mineralisation
      has been widely reported over the past years. However, operational problems
      related to the use of soluble iron salt as a homogeneous catalyst involve the
      development of novel catalysts that are able to operate in a wide pH range. For
      this purpose, polyvinyl alcohol-alginate beads, containing goethite as iron, were
      synthesised and evaluated as heterogeneous electro-Fenton catalyst for 1
      butylpyridinium chloride mineralisation. The influence of catalyst dosage and pH
      solution on ionic liquid degradation was analysed, achieving almost total
      oxidation after 60 min under optimal conditions (2 g/L catalyst concentration and
      pH 3). The results showed good catalyst stability and reusability, although its
      effectiveness decreases slightly after three successive cycles. Furthermore, a
      plausible mineralisation pathway was proposed based on the oxidation byproducts
      determined by chromatographic techniques. Finally, the Microtox(r) test revealed
      notable detoxification after treatment which demonstrates high catalyst ability
      for pyridinium-based ionic liquid degradation by the electro-Fenton process.

PMID- 29034427
TI  - Mosquito oviposition deterrents.
AB  - Mosquitoes are well-known vectors of disease and threaten the health of millions
      of people annually. While synthetic insecticides have been relied on to combat
      these diseases, insecticide resistance and environmental concerns have directed
      attention towards novel and more targeted mosquitocides derived from botanicals.
      Research on the activity of botanical derivatives has focused on mosquito larvae
      and adults with little attention given to their potential as oviposition
      deterrents against gravid female mosquitoes. This review explores the influence
      of chemical and biological factors on deterrence and examines issues relating to
      environmental persistence and non-target effects. With very few discoveries of
      new insecticide pathways, the answer to effective mosquito control may well
      reside within other ancient plant-based organisms that have co-resided and
      evolved with this ubiquitous pest.

PMID- 29034429
TI  - Toxicity studies of nanofabricated palladium against filariasis and malaria
      vectors.
AB  - The present study was carried out to establish the biofabrication of palladium
      nanoparticles (PdNPs) using the plant leaf extract of Tinospora cordifolia Miers
      and its toxicity studies on the larvae of filariasis vector, Culex
      quinquefasciatus Say and malaria vector, Anopheles subpictus Grassi. The
      biofabricated PdNPs were characterized by using UV-visible spectrum, FTIR, XRD,
      FESEM, EDX and HRTEM. HRTEM confirmed the PdNPs were slightly agglomerated and
      spherical in shape and the average size was 16 nm. Gas chromatography and mass
      spectrometry analysis result revealed that the major constituent present in the
      T. cordifolia leaf extract is 2,4-di-tert-butylphenol (31.79%) whereas the minor
      compounds are 1-hexadecanol (7.97%), 1-octadecanol (7.70%), 1-eicosanol (6.85%),
      behenic alcohol (5.36%), 1-tetradecene (6.22%), cyclotetradecane (6.23%), 1
      hexadecene (7.97%), 1-octadecene (7.70%), 1-eicosene (6.85%), and 1-docosene
      (5.36%). T. cordifolia leaf extract exhibited the larvicidal activity against the
      fourth instar larvae of C. quinquefasciatus and A. subpictus with the values of
      LC50 = 59.857 and 54.536 mg/L; LC90 = 113.445 and 108.940 mg/L, respectively. The
      highest toxicity was observed in the biofabricated PdNPs against the fourth
      instar larvae of C. quinquefasciatus and A. subpictus with the values of LC50 =
      6.090 and 6.454 mg/L; LC90 = 13.689 and 13.849 mg/L, respectively. Concerning non
      target effects, Poecilia reticulata were exposed to PdNPs for 24 h and did not
      exhibit any noticeable toxicity. Overall, our findings strongly suggest that
      PdNPs is a perfect ecological and inexpensive approach for the control of
      filariasis and malaria vectors.

PMID- 29034431
TI  - Cultivation-dependent and high-throughput sequencing approaches studying the co
      occurrence of antibiotic resistance genes in municipal sewage system.
AB  - During the past years, antibiotic-resistant bacteria (ARB) leading for the
      spreading of antibiotic resistance genes (ARGs) became a global problem,
      especially multidrug-resistant (MDR) bacteria are considered the prime culprit of
      antibiotic resistance. However, the correlation between the antibiotic-resistant
      phenotype and the ARG profiles remains poorly understood. In the present study,
      metagenomic functional screening and metagenomic analysis of coliforms were
      combined to explore the phenotype and genotype of the ARBs from municipal sewage.
      Our results showed that the ARG co-occurrence was widespread in the municipal
      sewage. The present study also highlighted the high abundance of ARGs from
      antibiotic resistance coliforms especially the MDR coliforms with ARG level of
      33.8 +/- 4.2 copies per cell. The ARG profiles and the antibiotic resistance
      phenotypes of the isolated antibiotic resistant coliforms were also correlated
      and indicated that the resistance to the related antibiotic (ampicillin,
      kanamycin, erythromycin, chloramphenicol, and tetracycline) was mostly
      contributed by the ARGs belonging to the subtypes of beta-lactamase,
      aminoglycoside 3-phosphotransferase, phosphotransferase type 2, chloramphenicol
      acetyltransferase, tetA, etc.

PMID- 29034430
TI  - Ultraviolet filters and heat shock proteins: effects in Chironomus riparius by
      benzophenone-3 and 4-methylbenzylidene camphor.
AB  - Benzophenone-3 (BP3) and 4-methylbenzylidene camphor (4MBC) are common
      ultraviolet filters (UV filters), compounds considered as emergent contaminants,
      used in different products like plastics and personal care products. The levels
      of these compounds are rising in the wild, but the effects they have on
      invertebrates are poorly understood. Chironomus riparius is a benthic insect
      widely used in toxicology, and several studies have been previously performed in
      our laboratory to determine the effects these compounds have on this organism at
      the molecular level. We have shown that UV filters can alter the mRNA levels of
      heat shock protein 70 (Hsp70), one of the most studied heat shock proteins.
      Although these proteins are crucial for the survival of organisms, little data is
      available on the effects these emergent contaminants have on them, especially in
      invertebrates. Here, we analyzed the transcriptional activity of 12 genes
      covering the different groups of heat shock protein [Hsp10, Hsp17, Hsp21, Hsp22,
      Hsp23, Hsp24, Hsp27, Hsp34, Hsp40, Hsp60, Hsc70 (3), and Hsc70 (4)] in response
      to 0.1 and 1 mg/L concentrations of BP3 and 4MBC at 8 and 24 h. The results
      showed that some small Hsp (sHsp) genes were altered by these compounds, while
      the genes of proteins present in mitochondria, Hsp10 and Hsp60, did not change.
      sHsps are also involved in developmental processes, so the observed variations
      could be due to the endocrine disruption activity described for these compounds
      rather than to a stress response.

PMID- 29034432
TI  - YKL071W from Saccharomyces cerevisiae encodes a novel aldehyde reductase for
      detoxification of glycolaldehyde and furfural derived from lignocellulose.
AB  - Aldehydes generated as by-products during the pretreatment of lignocellulose are
      the key inhibitors to Saccharomyces cerevisiae, which is considered as the most
      promising microorganism for industrial production of biofuel, xylitol as well as
      other special chemicals from lignocellulose. S. cerevisiae has the inherent
      ability to in situ detoxify aldehydes to corresponding alcohols by multiple
      aldehyde reductases. Herein, we report that an uncharacterized open reading frame
      YKL071W from S. cerevisiae encodes a novel "classical" short-chain
      dehydrogenase/reductase (SDR) protein with NADH-dependent enzymatic activities
      for reduction of furfural (FF), glycolaldehyde (GA), formaldehyde (FA), and
      benzaldehyde (BZA). This enzyme showed much better specific activities for
      reduction of GA and FF than FA and BZA, and displayed much higher Km and Kcat/Km
      but lower Vmax and Kcat for reduction of GA than FF. For this enzyme, the optimum
      pH was 5.5 and 6.0 for reduction of GA and FF, and the optimum temperature was 30
      degrees C for reduction of GA and FF. Both pH and temperature affected stability
      of this enzyme in a similar trend for reduction of GA and FF. Cu2+, Zn2+, Ni2+,
      and Fe3+ had severe inhibition effects on enzyme activities of Ykl071wp for
      reduction of GA and FF. Transcription of YKL071W in S. cerevisiae was
      significantly upregulated under GA and FF stress conditions, and its
      transcription is most probably regulated by transcription factor genes of YAP1,
      CAD1, PDR3, and STB5. This research provides guidelines to identify more
      uncharacterized genes with reductase activities for detoxification of aldehydes
      derived from lignocellulose in S. cerevisiae.

PMID- 29034433
TI  - Development of humanized scFv antibody fragment(s) that targets and blocks
      specific HLA alleles linked to myasthenia gravis.
AB  - Myasthenia gravis (MG) is an autoimmune disease caused by sensitization of the
      immune system to self-antigens. We have previously shown that targeting MG
      susceptible alleles can significantly inhibit proliferation of disease-specific T
      cells. In this work, we humanized a murine monoclonal antibody (mAb) LG11,
      capable of blocking MG-associated DQ beta 1 (DQB1) allele and reformatted it into
      single-chain fragment variable (scFv). A fully functional humanized scFv was
      obtained by optimizing variable domain orientations and linker lengths, along
      with the optimization of expression conditions and codons to suit Escherichia
      coli expression machinery. Characterization of humanized scFv (FL8) revealed that
      the reformatted scFv, despite recognizing the same epitope as the parent murine
      LG11 mAb, exhibited superior binding affinity (0.97 nM) compared to the LG11 mAb,
      towards the immunizing antigen (DQB1*0601/70-90) and was able to block the
      proliferation of T cells cultured from PBLs of MG-patients typed DQB1*0601. The
      scFv was also capable of binding a variant MG-associated allele (DQB1*0502/70-90)
      with moderate affinity (18.7 nM), a feature that was absent in the LG11. To our
      knowledge, this is the first report of humanizing a MG-associated human leukocyte
      antigen (HLA) scFv for preclinical studies.

PMID- 29034434
TI  - Genomic analyses reveal low mitochondrial and high nuclear diversity in the
      cyclosporin-producing fungus Tolypocladium inflatum.
AB  - Mitochondrial DNA is generally regarded to evolve faster than nuclear DNA in
      animals, whereas if this is also true in fungi remains unclear. Herein, we
      annotate the first complete mitochondrial genome (mitogenome) of the cyclosporin
      producing fungus Tolypocladium inflatum and report the genome-wide sequence
      variations among five isolates originating from distantly separated localities.
      We found that T. inflatum has among the most compact of fungal mitogenomes; its
      25 kb DNA molecule encodes all standard fungal mitochondrial genes and harbors
      only one intron. Transcriptional analyses validated the expression of most
      conserved genes. We found several uncommon repetitive elements and evidence of
      gene transfer from the mitochondrion to the nucleus. Phylogenetic analyses
      confirmed the placement of T. inflatum in the fungal order Hypocreales although
      there was uncertainty on its family-level affiliation. Comparative genomic
      analyses among the five isolates identified an overall lower level of
      intraspecific variation in mitogenomes than in nuclear genomes; however, both the
      nuclear and mitochondrial genomes revealed similar isolate relationships, not
      correlating with geographic sources of these isolates. Our study shed new
      insights into the evolution of the medicinally important ascomycete T. inflatum.

PMID- 29034436
TI  - Natalizumab therapy is associated with changes in serum JC virus antibody indices
      over time.
AB  - To examine changes in anti-JC Virus (JCV) index measurements over time in
      multiple sclerosis (MS) patients to better understand this test, which is used in
      assessing risk of progressive multifocal leukoencephalopathy (PML) with
      natalizumab. We aim to describe and compare seroconversion rates, variability of
      JCV antibody index values, and changes in index values over time between patients
      on natalizumab therapy and patients naive to natalizumab. Anti-JCV index values
      are used to help decide whether to start, continue, or stop treatment. Assessing
      how index values vary over time is interpreted to allow a patient's risk of PML
      to be better characterized. Retrospective analysis was conducted using records of
      patients with multiple JCV antibody index measurements exposed to therapy with
      natalizumab (N = 150) or not (N = 145). Rates of seroconversion, variability of
      indices, and changes in index values over time were calculated and compared.
      Patients on natalizumab who were initially JCV antibody negative seroconverted at
      a significantly higher rate than patients naive to natalizumab (23.9 vs. 9.1%, p
      < 0.01). Variability of anti-JCV indices was also found to be significantly
      higher for patients on natalizumab (p < 0.05). Patients on natalizumab
      additionally trended towards a larger increase in index values over time. Therapy
      with natalizumab was associated with higher rates of seroconversion and greater
      anti-JCV index variability, suggesting that therapy with natalizumab may
      influence this test used to assess risk of treatment with it.

PMID- 29034435
TI  - Advances in the Treatment of Paraproteinemic Neuropathy.
AB  - Purpose of review Several advances have been made on the pathogenesis and therapy
      of neuropathies associated with paraproteinemia (monoclonal gammopathy). It is
      important for the neurologist to understand the pathogenetic relevance of this
      association especially when the hematological disease does not require per se any
      therapy. Recent findings Treatment of the neuropathy in patients with malignant
      paraproteinemia is mainly addressed by the hematologist while the neurologist is
      mainly involved in the initial diagnosis and in deciding whether the neuropathy
      is caused by the disease or by the chemotherapy used for the disease. There is
      little evidence that the neuropathy is caused by the hematological condition in
      patients with IgG or IgA monoclonal gammopathy of undetermined significance
      (MGUS) unless there is an evidence of a reactivity of the paraprotein with nerve
      or evidence of its presence in the nerve. Patients with a chronic inflammatory
      demyelinating polyradiculoneuropathy (CIDP)-like presentation should be treated
      as CIDP while there is no evidence that immune or chemotherapy may be effective
      in the other patients. In most patients with IgM paraproteinemia, that is usually
      a MGUS or an indolent Waldenstrom's macroglobulinemia, the neuropathy is induced
      by an immune reactivity of the paraprotein with nerve and particularly with the
      myelin-associated glycoprotein. There are now consistent data also from
      controlled studies that the anti-CD20 monoclonal antibody rituximab may improve
      the neuropathy in these patients. POEMS syndrome is a severe condition
      characterized by a disabling neuropathy whose prognosis has improved in the last
      few years with therapies against the proliferating plasma cell clone or vascular
      endothelial growth factor including local radiotherapy and chemotherapy followed
      by autologous stem cell transplantation. Other therapies are also available for
      patients not eligible or resistant to transplantation, including lenalidomide and
      possibly thalidomide or bortezomib. Summary Several new therapies are now
      available for patients with paraproteinemic neuropathy consistently improving the
      prognosis of these neuropathies. In most instances, however, their efficacy needs
      to be confirmed in controlled trials.

PMID- 29034438
TI  - The Pathways fertility preservation decision aid website for women with cancer:
      development and field testing.
AB  - PURPOSE: To improve survivors' awareness and knowledge of fertility preservation
      counseling and treatment options, this study engaged survivors and providers to
      design, develop, and field-test Pathways: a fertility preservation patient
      decision aid website for young women with cancer(c). METHODS: Using an adapted
      user-centered design process, our stakeholder advisory group and research team
      designed and optimized the Pathways patient decision aid website through four
      iterative cycles of review and revision with clinicians (n = 21) and survivors (n
      = 14). Field-testing (n = 20 survivors) assessed post-decision aid scores on the
      Fertility Preservation Knowledge Scale, feasibility of assessing women's decision
      making values while using the website, and website usability/acceptability
      ratings. RESULTS: Iterative stakeholder engagement optimized the Pathways
      decision aid website to meet survivors' and providers' needs, including providing
      patient-friendly information and novel features such as interactive value
      clarification exercises, testimonials that model shared decision making,
      financial/referral resources, and a printable personal summary. Survivors scored
      an average of 8.2 out of 13 (SD 1.6) on the Fertility Preservation Knowledge
      Scale. They rated genetic screening and having a biological child as strong
      factors in their decision-making, and 71% indicated a preference for egg
      freezing. Most women (> 85%) rated Pathways favorably, and all women (100%) said
      they would recommend it to other women. CONCLUSIONS: The Pathways decision aid is
      a usable and acceptable tool to help women learn about fertility preservation.
      IMPLICATIONS FOR CANCER SURVIVORS: The Pathways decision aid may help women make
      well-informed values-based decisions and prevent future infertility-related
      distress.

PMID- 29034437
TI  - Management of early anal cancer: need for guidelines and standardisation.
AB  - PURPOSE: The optimal management of early squamous cell carcinoma of the anal
      canal (AC) is yet to be determined. This study investigated current practice in
      the management of early AC. METHODS: A patterns of care survey was completed by
      Australian surgeons and radiation oncologists. Specific topics addressed were as
      follows: geographical location of practice, staging of disease, treatment
      approaches to T1N0 tumours and grade 3 anal intra-epithelial neoplasia (AIN3)
      lesions, radiotherapy planning, toxicities, follow-up and clinical trial
      involvement. RESULTS: Sixty-four responses were obtained. For the management of
      T1N0 disease, half the respondents recommended standard dose chemo-radiotherapy
      (CRT) and one third recommended wide local excision (WLE). For the management of
      AIN3, half recommended WLE while a quarter advocated observation. CONCLUSIONS:
      This study reveals a significant variation in the management of early AC. The
      development of guidelines specific to the treatment of early AC could standardise
      treatment while further research is required to define the optimal management of
      T1N0 AC and AIN.

PMID- 29034439
TI  - Low-grade small intestinal bacterial overgrowth is common in patients with non
      alcoholic steatohepatitis on quantitative jejunal aspirate culture.
AB  - BACKGROUND: Though pathogenesis of non-alcoholic steatohepatitis (NASH) is
      unclear, association with small intestinal bacterial overgrowth [SIBO] and fecal
      dysbiosis is suggested. We evaluated SIBO in NASH using quantitative jejunal
      aspirate culture (conventional criteria: >= 105 colony forming unit (CFU)/mL and
      newer cutoff >= 103 CFU/mL) and glucose hydrogen breath test. METHODS: Thirty
      eight patients with NASH (age 37.5 years, range 20-54, 9, 24% female), diagnosed
      by ultrasonography, alanine aminotransferase >1.5 times normal and liver biopsy
      (in 27/38, 71%) and exclusion of other causes and 12 constipation-predominant
      irritable bowel syndrome as historical controls (age 39.5-y, 26-44; 3, 25%
      female) without fatty liver were studied. RESULTS: Jejunal aspirates, obtained in
      35/38 patients, were sterile in 14/35 (40%) and bacteria isolated in 21 (60%)
      (all aerobic, in one anaerobe also; Gram positive 5, negative 13, both 3). In
      contrast, bacteria (two Gram negative) were isolated in 3/12 (25%) controls (odds
      ratio 4.5, 95% CI 1.0-19.5; p = 0.04); colony counts were higher in NASH than
      controls (median 380 CFU/mL, 0-200,000 vs. 0 CFU/mL, 0-1000; p = 0.02). Gram
      negative bacteria tended to be commoner in NASH than controls (16/35 vs. 2/12; p
      = 0.07). Seven out of 35 (20%) patients with NASH (>= 105 CFU/mL in 5 and 2 other
      on glucose hydrogen breath test) and no control had SIBO (p = ns); low-grade SIBO
      (>=103 CFU/mL) was commoner in NASH than controls (14/35, 40%, vs. 1/12, 8.3%; p
      = 0.04). There was no correlation between bacterial colony count and bacterial
      type and anthropometric and biochemical parameters. CONCLUSION: Low-grade
      bacterial overgrowth, particularly with Gram negative bacteria, was commoner in
      NASH than controls.

PMID- 29034440
TI  - Risperidone-induced metabolic dysfunction is attenuated by Curcuma longa extract
      administration in mice.
AB  - Antipsychotics, such as risperidone, increase food intake and induce alteration
      in glucose and lipid metabolism concomitantly with overweight and body fat
      increase, these biological abnormalities belong to the metabolic syndrome
      definition (high visceral adiposity, hypertriglyceridemia, hyperglycemia, low HDL
      cholesterol and high blood pressure). Curcumin is a major component of
      traditional turmeric (Curcuma longa) which has been reported to improve lipid and
      glucose metabolism and to decrease weight in obese mice. We questioned the
      potential capacity of curcumin, contained in Curcuma longa extract
      (BiocurcumaTM), to attenuate the risperidone-induced metabolic dysfunction. Two
      groups of mice were treated once a week, for 22 weeks, with intraperitoneal
      injection of risperidone (Risperdal) at a dose 12.5 mpk. Two other groups
      received intraperitoneal injection of the vehicle of Risperdal following the same
      schedule. Mice of one risperidone-treated groups and of one of vehicle-treated
      groups were fed a diet with 0.05% BiocurcumaTM (curcumin), while mice of the two
      other groups received the standard diet. Curcumin limited the capacity of
      risperidone to reduce spontaneous motricity, but failed to impede risperidone
      induced increase in food intake. Curcumin did not reduce the capacity of
      risperidone to induce weight gain, but decreased visceral adiposity and decreased
      the risperidone-induced hepatomegaly, but not steatosis. Furthermore, curcumin
      repressed the capacity of risperidone to induce the hepatic over expression of
      enzymes involved in lipid metabolism (LXRalpha, FAS, ACC1, LPL, PPARgamma, ACO,
      SREBP2) and decreased risperidone-induced glucose intolerance and
      hypertriglyceridemia. Curcumin decreased risperidone-induced increases in serum
      markers of hepatotoxicity (ALAT, ASAT), as well as of one major hepatic pro
      inflammatory transcription factor (NFkappaB: p105 mRNA and p65 protein). These
      findings support that nutritional doses of curcumin contained in Curcuma longa
      extract are able to partially counteract the risperidone-induced metabolic
      dysfunction in mice, suggesting that curcumin ought to be tested to reduce the
      capacity of risperidone to induce the metabolic syndrome in human.

PMID- 29034443
TI  - Prospective clinical study comparing intraligamentary anesthesia and inferior
      alveolar nerve block for extraction of posterior mandibular teeth.
AB  - OBJECTIVES: The aim of the study was to compare the efficacy of intraligamentary
      anesthesia (ILA) with conventional inferior alveolar nerve block (IANB) for
      extraction of mandibular posterior teeth. MATERIALS AND METHODS: In a prospective
      clinical trial, a total of 301 mandibular posterior teeth were extracted in 266
      patients. Randomization was conducted into those who received ILA (patients n =
      98; teeth n = 105) and those who received IANB (patient n = 140; teeth n = 140).
      Twenty-eight patients were subjected to bilateral mandibular dental extractions
      and received both ILA und IANB (teeth n = 56 (ILA n = 28; IANB n = 28)). The
      primary objective was to evaluate the differences in pain during injection, in
      pain during tooth extraction (numeric rating scale (NRS)), and in anesthetic
      quality (complete/sufficient vs. insufficient/no effect). Differences in latency
      time, amount of anesthetic solution, need for second injection, and duration of
      local numbness as well as in the incidence of dry socket were assessed. RESULTS:
      ILA had significant lower pain of injection (p < 0.001), shorter latency time (p
      < 0.001), and shorter duration of local numbness (p < 0.001) and required lesser
      amount of local anesthetic solution (p < 0.001) together with a similar
      anesthetic quality (p = 0.082) compared to IANB. Concerning pain during
      extraction (p = 0.211), frequency of second injection (p = 0.197), and incidence
      of dry socket (p = 0.178), no significant differences were detected. CONCLUSION:
      ILA fulfills the requirements of a minimal invasive and patient-friendly local
      anesthetic technique. In accordance, it represents a safe and reliable
      alternative to IANB for extraction of mandibular posterior teeth. CLINICAL
      RELEVANCE: ILA can be recommended for routine dental extractions.

PMID- 29034441
TI  - The Oral Pretreatment of Glycyrrhizin Prevents Surgery-Induced Cognitive
      Impairment in Aged Mice by Reducing Neuroinflammation and Alzheimer's-Related
      Pathology via HMGB1 Inhibition.
AB  - Neuroinflammation and Alzheimer's-related pathology play essential roles in
      postoperative cognitive dysfunction (POCD). High-mobility group box 1 (HMGB1) is
      well known as a pivotal mediator in neuroinflammation, and its associations with
      Alzheimer's-related pathology and POCD have been also revealed. Glycyrrhizin is a
      nature inhibitor of HMGB1 and is reported with neuroprotective effects through
      oral administration. Therefore, the present study aims to test the hypothesis
      that the oral pretreatment of glycyrrhizin prevents POCD by inhibiting HMGB1
      induced neuroinflammation and Alzheimer's-related pathology in aged mice. Aged
      male C57BL/6 mice were subjected to the splenectomy surgery under general
      anesthesia and the oral pretreatment of glycyrrhizin. The postoperative cognitive
      changes were evaluated by using Morris water maze (MWM) test. The protein
      expressions of HMGB1, TLR4, NF-kappaB, p-Tau, and pro-inflammatory cytokines were
      determined by Western blot assay. The hippocampal level of beta-amyloid (Abeta)
      was assessed by ELISA assay. We found that the oral pretreatment of glycyrrhizin
      inhibited HMGB1 cytosolic expression, increased the PSD-95 protein expression,
      and attenuated the severity of postoperative memory impairment, as indicated by
      the shorter swimming latency and distance in MWM trials when compared with the
      mice subjected to the surgery alone. Additionally, the pretreatment of
      glycyrrhizin reduced the postoperative neuroinflammation (production of pro
      inflammatory cytokines including IL-1beta, TNF-alpha, and IL-6 as well as NF
      kappaB nuclear expression) and Alzheimer's-related pathology (Tau phosphorylation
      at the site of AT-8 and Ser396 as well as Abeta40 and 42 concentrations) in the
      hippocampus of the aged mice undergoing splenectomy surgery. In conclusion, our
      results suggest that the oral pretreatment of glycyrrhizin can prevent the
      postoperative cognitive impairment by reducing neuroinflammation and Alzheimer's
      related pathology in the hippocampus of aged mice via HMGB1 inhibition.

PMID- 29034442
TI  - Correlation between tissue expression of microRNA-137 and CD8 in oral lichen
      planus.
AB  - OBJECTIVES: Oral lichen planus (OLP) is a chronic, inflammatory condition,
      classified by the World Health Organization as a premalignant lesion. We
      performed this study to evaluate the correlation between microRNA-137 (miR-137)
      and CD8 oral tissue expression in OLP patients. MATERIALS AND METHODS: Twenty OLP
      patients [classified into three groups: (a) papular, reticular, or plaque; (b)
      atrophic; and (c) erosive] and 20 healthy controls were subjected to biopsy of
      the oral mucosa. To evaluate CD8 tissue expression, we performed
      immunohistochemical examination, followed by immunostaining and computerized
      quantification. The expression of miR-137 was evaluated using real-time
      quantitative PCR. We used SPSS software (version 15 for windows) to perform the
      statistical analysis. RESULTS: Our analysis showed an increased tissue expression
      of CD8 (p < 0.01) and reduced expression of miR-137 (p < 0.001) in OLP patients,
      compared to the control group. Moreover, there was a statistically significant
      difference (p = 0.001) between OLP subgroups in terms of CD8 tissue expression
      [highest in erosive OLP and lowest in papular/reticular/plaque OLP]. However,
      these subgroups showed no significant difference (p = 0.168) in terms of miR-137
      expression. A negative correlation (p < 0.05) between tissue expression of miR
      137 and CD8 was noted with a varying correlation coefficient in different OLP
      subgroups (-0.250 in erosive OLP, -0.491 in atrophic OLP and -0.616 in
      papular/reticular/plaque OLP). CONCLUSIONS: Our findings indicate reduced
      expression of miR-137 and a reverse correlation between tissue expression of miR
      137 and CD8 in the oral mucosa of OLP patients. CLINICAL RELEVANCE: Future
      studies should investigate the therapeutic potential of miR-137 overexpression in
      OLP patients.

PMID- 29034444
TI  - MAGE-A11 expression contributes to cisplatin resistance in head and neck cancer.
AB  - OBJECTIVE: The objective of this study is to investigate the roles of melanoma
      associated antigens (MAGEs) in the cisplatin treatment of head and neck cancer.
      MATERIALS AND METHODS: We assessed the efficacy of cisplatin in a set of four
      head and neck cancer cell lines using a crystal violet assay. The MAGE-A
      expression in all cell lines was measured with RT-qPCR. The correlation between
      MAGE-A expression and cisplatin efficacy was investigated using Spearman's
      correlation analysis. Furthermore, we established a cell line with stable
      overexpression of MAGE-A11 and determined influence on proliferation, cisplatin
      efficacy and cell apoptosis. In this cell line, the effects of cisplatin were
      assessed using either crystal violet assays or flow cytometry (Annexin V).
      RESULTS: For MAGE-A11, we observed the highest correlation (r = 1.000, p =
      0.0417) with low cisplatin efficacy. Stable overexpression of MAGE-A11 resulted
      in no changes in proliferation, but in lower cisplatin cytotoxicity and lower
      rates of apoptosis. Also, mouse double minute 2 homolog (MDM2) expression was
      induced by MAGE-A11 overexpression. CONCLUSION: We provide evidence that MAGE-A11
      expression contributes to cisplatin resistance in head and neck cancer. CLINICAL
      RELEVANCE: Our study underscores the negative predictive role of MAGE-A11
      expression in head and neck cancer.

PMID- 29034445
TI  - Dental prevention and disease awareness in children with congenital heart
      disease.
AB  - OBJECTIVES: The importance of excellent oral health is known to be crucial in
      children with congenital heart diseases (CHD). Data about dental health and
      disease awareness is limited. This study aims to assess preventive measures taken
      to improve dental health in children with CHD and to gain insight into disease
      awareness and knowledge about the importance of oral health in children with CHD
      and to propose measures that could be taken. MATERIAL AND METHODS: Parents of 150
      children with CHD were asked to complete a questionnaire containing specific
      questions about the preventive measures taken by the parents and dental and
      medical practitioners and their knowledge about underlying disease and the
      importance of oral health. RESULTS: Our results show an absence of information in
      parents concerning preventive measures and oral hygiene. Knowledge of the
      indications for antibiotic prophylaxis and for actually given medications was
      lacking. Preventive dental measures were not performed according to current
      guidelines. CONCLUSIONS: Knowledge of parents about the importance of oral health
      in children with CHD could be improved. However, specialized centers involving
      pediatric cardiologists and pediatric dentists could coordinate the education of
      parents at an early stage. Moreover, general dentists should be trained more
      frequently concerning the indications for antibiotic prophylaxis, in particular,
      and the dental care of children with chronic diseases, in general. Warning cards
      such as the heart pass should be issued to parents of children with CHD. CLINICAL
      RELEVANCE: The current study reveals the need for the structured training of
      medical and dental practitioners to support parents of children with CHD.

PMID- 29034446
TI  - Glucose Variability After Bariatric Surgery: Is Prediction of Diabetes Remission
      Possible?
AB  - We aimed to corroborate glycemic control after bariatric surgery (BS) using
      continuous glucose monitoring (CGM) and analyze if data could predict long-term
      outcome. We evaluated 24 of our patients with type 2 diabetes who underwent BS
      (12 Roux-en-Y gastric bypass, RYGB, and 12 single-anastomosis duodeno-ileal
      bypass with sleeve gastrectomy, SADI-S) and who were in remission after 18-24
      months' follow-up. At this time, a CGM device was placed for 7 days. Patients
      were reevaluated thereafter for at least 5 years. Glucose variability (GV) was
      lower in patients after SADI-S and in the 18 patients who were still in remission
      after 5 years, and provided more information on long-term status than classical
      diabetes-related characteristics.

PMID- 29034448
TI  - Synergies From Integrating Randomized Controlled Trials and Real-World Data
      Analyses.
AB  - Analyses using administrative claims databases or national registries provide
      estimates of benefits and harms of medications in real-world settings for large
      and diverse patient populations. Whereas claims-based nonrandomized studies and
      randomized-controlled trials (RCTs) have distinct limitations, their strengths
      are complementary. Integrating RCT and claims data offers substantial synergies.
      We propose obtaining routinely collected longitudinal claims data from RCT
      participants and discuss the added value of the novel evidence that can be
      derived from this "information overlap."

PMID- 29034447
TI  - Distilling Heterogeneity among Children with Disruptive Behavior: Associations
      between Symptom Patterns and Social Functioning.
AB  - Children with disruptive behavior (DB) are a heterogeneous group who exhibit
      several characteristics that may contribute to poor social functioning. The
      present study identified profiles of reactive aggression, proactive aggression,
      callous-unemotional (CU) traits, and prosocial behavior in a sample of children
      with DB. Associations with social functioning (social interaction, social status)
      were then examined, along with sex differences in profile membership. Parent
      ratings of 304 clinic-referred children ages 6-12 years with DB were analyzed
      using latent profile analysis. Five profiles were identified: 1) Moderate
      prosocial behavior, reactive aggression, and CU, and low proactive aggression
      (labelled Moderate); 2) Relatively high prosocial behavior and low reactive and
      proactive aggression and CU traits (Prosocial); 3) High prosocial behavior and
      reactive aggression, moderate proactive aggression, and low-moderate CU (Reactive
      Prosocial); 4) Low prosocial behavior, high CU, high-moderate reactive
      aggression, and low-moderate proactive aggression (Reactive-CU); and 5) Low
      prosocial behavior and high reactive and proactive aggression and CU (Aggressive
      CU). Profiles characterized by CU traits, reactive aggression, and low prosocial
      behavior were associated with the most problematic parent-rated social
      interaction and social status. The results highlight the need to differentiate
      profiles of psychopathology in children with DB to better address factors most
      associated with social functioning.

PMID- 29034449
TI  - Nitrous oxide-based vs. nitrous oxide-free general anaesthesia and accidental
      awareness in surgical patients: an abridged Cochrane systematic review.
AB  - Accidental awareness during general anaesthesia can arise from a failure to
      deliver sufficient anaesthetic agent, or from a patient's resistance to an
      expected sufficient dose of such an agent. Awareness is 'explicit' if the patient
      is subsequently able to recall the event. We conducted a systematic review into
      the effect of nitrous oxide used as part of a general anaesthetic on the risk of
      accidental awareness in people over the age of five years undergoing general
      anaesthesia for surgery. We included 15 randomised controlled trials, 14 of
      which, representing a total of 3439 participants, were included in our primary
      analysis of the frequency of accidental awareness events. The awareness incidence
      rate was rare within these studies, and all were considered underpowered with
      respect to this outcome. The risk of bias across all studies was judged to be
      high, and 76% of studies failed adequately to conceal participant allocation. We
      considered the available evidence to be of very poor quality. There were a total
      of three accidental awareness events reported in two studies, one of which
      reported that the awareness was the result of a kink in a propofol intravenous
      line. There were insufficient data to conduct a meta- or sub-group analysis and
      there was insufficient evidence to draw outcome-related conclusions. We can,
      however, recommend that future studies focus on potentially high-risk groups such
      as obstetric or cardiac surgery patients, or those receiving neuromuscular
      blocking drugs or total intravenous anaesthesia.

PMID- 29034450
TI  - New Onset Focal Stabbing Headache Associated With Peripheral Vertigo: A Case
      Report.
AB  - We present a novel case of a focal stabbing headache sharing features of primary
      stabbing headache that started and resolved with the onset and resolution of a
      course of self-limiting peripheral vertigo. The association of onset and
      improvement of the stabbing headaches support the trigeminal and vestibular
      reciprocal relationships. Vestibular input may be the driving force and a
      potential target for treatment.

PMID- 29034451
TI  - Cortical light scattering during interictal epileptic spikes in frontal lobe
      epilepsy in children: A fast optical signal and electroencephalographic study.
AB  - OBJECTIVE: Interictal epileptic spikes (IES) represent a signature of the
      transient synchronous and excessive discharge of a large ensemble of cortical
      heterogeneous neurons. Epilepsy cannot be reduced to a hypersynchronous
      activation of neurons whose functioning is impaired, resulting on
      electroencephalogram (EEG) in epileptic seizures or IES. The complex
      pathophysiological mechanisms require a global approach to the interactions
      between neural synaptic and nonsynaptic, vascular, and metabolic systems. In the
      present study, we focused on the interaction between synaptic and nonsynaptic
      mechanisms through the simultaneous noninvasive multimodal multiscale recording
      of high-density EEG (HD-EEG; synaptic) and fast optical signal (FOS;
      nonsynaptic), which evaluate rapid changes in light scattering related to changes
      in membrane configuration occurring during neuronal activation of IES. METHODS:
      To evaluate changes in light scattering occurring around IES, three children with
      frontal IES were simultaneously recorded with HD-EEG and FOS. To evaluate change
      in synchronization, time-frequency representation analysis of the HD-EEG was
      performed simultaneously around the IES. To independently evaluate our multimodal
      method, a control experiment with somatosensory stimuli was designed and applied
      to five healthy volunteers. RESULTS: Alternating increase-decrease-increase in
      optical signals occurred 200 ms before to 180 ms after the IES peak. These
      changes started before any changes in EEG signal. In addition, time-frequency
      domain EEG analysis revealed alternating decrease-increase-decrease in the EEG
      spectral power concomitantly with changes in the optical signal during IES. These
      results suggest a relationship between (de)synchronization and neuronal volume
      changes in frontal lobe epilepsy during IES. SIGNIFICANCE: These changes in the
      neuronal environment around IES in frontal lobe epilepsy observed in children, as
      they have been in rats, raise new questions about the synaptic/nonsynaptic
      mechanisms that propel the neurons to hypersynchronization, as occurs during IES.
      We further demonstrate that this noninvasive multiscale multimodal approach is
      suitable for studying the pathophysiology of the IES in patients.

PMID- 29034452
TI  - Innovation Incentives and Biomarkers.
AB  - Previously, we have discussed the importance of economic incentives in shaping
      markets for precision medicines. Here we consider incentives for biomarker
      development, including discovery and establishment. Biomarkers can reveal
      valuable information regarding diagnosis and prognosis, predict treatment
      efficacy or toxicity, serve as markers of disease progression, and serve as
      auxiliary endpoints for clinical trials. Some have multiple uses, while others
      have a specialized role, resulting in diverse incentives across players in the
      healthcare system.

PMID- 29034453
TI  - AVP-825 (Sumatriptan Nasal Powder) Reduces Nausea Compared to Sumatriptan
      Tablets: Results of the COMPASS Randomized Clinical Trial.
AB  - BACKGROUND: Migraine-related nausea is associated with significant disability,
      increased burden of disease, and personal distress. Nausea can lead to delays or
      avoidance of initiating oral migraine treatment, sometimes resulting in treatment
      failures and poor outcomes. Nausea is often a symptom of migraine, but nausea may
      also be a consequence of treatment (ie, treatment emergent nausea [TEN]).
      Relieving nausea and minimizing TEN are important goals in acute migraine
      therapy. METHODS: We analyzed data from the COMPASS study, a randomized, double
      blind, double-dummy, comparative efficacy study that contrasted two active
      treatments, AVP-825 (breath-powered intranasal delivery of powdered sumatriptan
      22 mg) and oral sumatriptan tablets (100 mg). Three-level logistic multilevel
      models were used to examine longitudinal changes in nausea from three distinct
      perspectives across multiple attacks. Model 1 (Overall Nausea) examined
      longitudinal change in nausea from pre-dose through 120 minutes post-dose for the
      entire sample, independent of baseline nausea. Model 2 examined TEN from 10
      minutes through 120 minutes post-dose in attacks free of nausea at baseline to
      investigate whether or not nausea developed following treatment. Model 3 examined
      Nausea Relief from 10 minutes through 120 minutes post-dose in eligible attacks
      with nausea at baseline to examine whether or not nausea was relieved over the
      first 2 hours post-dose. Models tested for differences in rate of change in
      nausea over time and odds of nausea at specific time-points. RESULTS:
      Longitudinal nausea trajectories differed for AVP-825 and oral sumatriptan in the
      Overall Nausea model (Model 1) and TEN model (Model 2), but were more comparable
      across treatments for the Nausea Relief (Model 3). More specifically, in the
      Overall Nausea model (Model 1), an individual treating an attack with AVP-825 had
      a significantly faster decrease in nausea through the first 60 minutes post-dose
      and reduced odds of nausea at each time-point from 30 minutes through 120 minutes
      post-dose compared to oral sumatriptan. In Model 2, an individual's risk for TEN
      increased at a significantly faster rate through the first 45 minutes post-dose
      when treating an attack with oral sumatriptan, with significantly greater odds of
      experiencing TEN at 45, 60, and 90 minutes post-dose compared to AVP-825. The
      Nausea Relief model (Model 3) showed similar rates of change in nausea over time
      for the two treatments, but there was a constant difference in nausea level
      leading to reduced odds of nausea when treating with AVP-825 compared to oral
      sumatriptan. CONCLUSIONS: All three longitudinal models showed that AVP-825 had
      more favorable nausea outcomes compared to oral sumatriptan. AVP-825 treatment
      led to more rapid early reductions in Overall Nausea rates during the first hour,
      reduced odds of nausea from 30 minutes to 2 hours following treatment and reduced
      risk of TEN compared to oral sumatriptan. These results highlight the importance
      of separately assessing TEN and Nausea Relief in acute treatment trials of
      migraine.

PMID- 29034454
TI  - Successful treatment of SAPHO syndrome with apremilast.
AB  - SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a rare
      disease with inflammatory osteoarticular and skin involvement. The pathogenesis
      of SAPHO syndrome remains unclear, but evidence suggests it may be an
      autoinflammatory disease triggered upon exposure to infectious agents in
      genetically predisposed individuals. Induction of the interleukin (IL)-23/T
      helper 17 axis in addition to neutrophil activation seem to play a key role, and
      therapies targeting these immunological pathways, including tumour necrosis
      factor (TNF) inhibitors, ustekinumab, secukinumab and the IL-1 inhibitor
      anakinra, are potential treatment options that need further investigation. Here
      we report a case of a 24-year-old woman with SAPHO syndrome who presented at our
      clinic with palmoplantar pustulosis and sternoclavicular joint involvement.
      Previous treatments with topical steroids and keratolytics combined with
      nonsteroidal anti-inflammatory drugs, intravenous methylprednisolone,
      methotrexate and sulfasalazine had all failed to improve symptoms. Therapy with
      etanercept was not tolerated, and because of a previous demyelinating peripheral
      neuropathy, further treatment with TNF inhibitors was avoided. We initiated
      ustekinumab 45 mg, which improved skin manifestations but not joint pain. Dose
      escalation to 90 mg initially improved joint pain, but the dose had to be reduced
      to 45 mg again because of increased infections. During subsequent 45-mg
      ustekinumab treatment, joint pain exacerbated so we switched to adalimumab which
      caused an exacerbation of the disease, so we switched to secukinumab, which
      improved skin and joint symptoms significantly but was associated with a pustular
      hypersensitivity reaction. Finally, we began treatment with apremilast, a pan
      cytokine approach, resulting in stabilization of the skin and joint symptoms
      without side-effects. To our knowledge, this is the first case report of
      apremilast as a treatment for SAPHO syndrome.

PMID- 29034455
TI  - Diagnosis in the age of massive computing power.

PMID- 29034456
TI  - Trait-fitness relationships determine how trade-off shapes affect species
      coexistence.
AB  - Trade-offs between functional traits are ubiquitous in nature and can promote
      species coexistence depending on their shape. Classic theory predicts that convex
      trade-offs facilitate coexistence of specialized species with extreme trait
      values (extreme species) while concave trade-offs promote species with
      intermediate trait values (intermediate species). We show here that this
      prediction becomes insufficient when the traits translate non-linearly into
      fitness which frequently occurs in nature, e.g., an increasing length of spines
      reduces grazing losses only up to a certain threshold resulting in a saturating
      or sigmoid trait-fitness function. We present a novel, general approach to
      evaluate the effect of different trade-off shapes on species coexistence. We
      compare the trade-off curve to the invasion boundary of an intermediate species
      invading the two extreme species. At this boundary, the invasion fitness is zero.
      Thus, it separates trait combinations where invasion is or is not possible. The
      invasion boundary is calculated based on measurable trait-fitness relationships.
      If at least one of these relationships is not linear, the invasion boundary
      becomes non-linear, implying that convex and concave trade-offs not necessarily
      lead to different coexistence patterns. Therefore, we suggest a new ecological
      classification of trade-offs into extreme-favoring and intermediate-favoring
      which differs from a purely mathematical description of their shape. We apply our
      approach to a well-established model of an empirical predator-prey system with
      competing prey types facing a trade-off between edibility and half-saturation
      constant for nutrient uptake. We show that the survival of the intermediate prey
      depends on the convexity of the trade-off. Overall, our approach provides a
      general tool to make a priori predictions on the outcome of competition among
      species facing a common trade-off in dependence of the shape of the trade-off and
      the shape of the trait-fitness relationships.

PMID- 29034457
TI  - Regenerative Musculoskeletal Care: Ensuring Practice Implementation.

PMID- 29034460
TI  - Culture and Family Process: Measures of Familism for Filipino and Korean American
      Parents.
AB  - This study tests the psychometric properties of multiple survey items and scales
      that are either underused or newly developed to assess familism among Asian
      Americans. Using data collected from 150 Filipino and 188 Korean American parents
      (mostly mothers) in the Midwest region in 2013, the measures were examined for
      validity and reliability for each group and, when appropriate, for cross-cultural
      equivalence across the groups. Several scales and their items showed high quality
      psychometric properties and are ready for use to more accurately assess family
      process of each target group and to conduct comparative analyses. The findings
      also show that, contrary to the expectation, Filipino American families express
      more traditional aspects of familism than do Korean American families, and are
      more likely to reinforce traditional familism beliefs and behaviors among their
      children. This study reinforces a need for more empirical- and subgroup-specific
      research effort.

PMID- 29034461
TI  - The Migraine Attack as a Homeostatic, Neuroprotective Response to Brain Oxidative
      Stress: Preliminary Evidence for a Theory.
AB  - BACKGROUND: Previous research has suggested that migraineurs show higher levels
      of oxidative stress (lipid peroxides) between migraine attacks and that migraine
      triggers may further increase brain oxidative stress. Oxidative stress is
      transduced into a neural signal by the TRPA1 ion channel on meningeal pain
      receptors, eliciting neurogenic inflammation, a key event in migraine. Thus,
      migraines may be a response to brain oxidative stress. RESULTS: In this article,
      a number of migraine components are considered: cortical spreading depression,
      platelet activation, plasma protein extravasation, endothelial nitric oxide
      synthesis, and the release of serotonin, substance P, calcitonin gene-related
      peptide, and brain-derived neurotrophic factor. Evidence is presented from in
      vitro research and animal and human studies of ischemia suggesting that each
      component has neuroprotective functions, decreasing oxidant production,
      upregulating antioxidant enzymes, stimulating neurogenesis, preventing apoptosis,
      facilitating mitochondrial biogenesis, and/or releasing growth factors in the
      brain. Feedback loops between these components are described. Limitations and
      challenges to the model are discussed. CONCLUSIONS: The theory is presented that
      migraines are an integrated defensive, neuroprotective response to brain
      oxidative stress.

PMID- 29034459
TI  - Amelioration of autoimmunity with an inhibitor selectively targeting all active
      centres of the immunoproteasome.
AB  - BACKGROUND AND PURPOSE: Multicatalytic endopeptidase complex-like-1 (beta2i), low
      molecular mass polypeptide (LMP) 2 (beta1i) and LMP7 (beta5i) are the
      proteolytically active subunits of the immunoproteasome, a special type of
      proteasome mainly expressed in haematopoietic cells. Targeting LMP7 has been
      shown to be therapeutically effective in preclinical models of autoimmune
      diseases. In this study, we investigated the selectivity and biological activity
      of LU-005i, a recently described inhibitor of the immunoproteasome. EXPERIMENTAL
      APPROACH: The specificity of LU-005i and other immunoproteasome-selective
      inhibitors was characterized using fluorogenic peptide substrates. The effect of
      proteasome inhibition on cytokine release was investigated in endotoxin
      stimulated mouse splenocytes or human peripheral blood mononuclear cells (PBMCs).
      The effect of proteasome inhibition on inflammatory bowel disease in the dextran
      sulfate sodium (DSS)-induced colitis model was assessed by measuring weight loss
      and colon length. KEY RESULTS: LU-005i is the first human and mouse
      immunoproteasome-selective inhibitor that targets all three proteolytically
      active immunoproteasome subunits. LU-005i inhibited cytokine secretion from
      endotoxin-stimulated mouse splenocytes or human PBMCs. Furthermore,
      differentiation of naive T helper cells to T helper 17 cells was impaired in the
      presence of LU-005i. Additionally, LU-005i ameliorated DSS-induced colitis.
      CONCLUSION AND IMPLICATIONS: This study with a novel pan-immunoproteasome
      inhibitor substantiates that the immunoproteasome is a promising drug target for
      the treatment of inflammatory diseases and that exclusive inhibition of LMP7 is
      not necessary for therapeutic effectiveness. Our results will promote the design
      of new generations of immunoproteasome inhibitors with optimal therapeutic
      efficacy for clinical use in the treatment of autoimmunity and cancer.

PMID- 29034462
TI  - A Model-Based Cluster Analysis of Maternal Emotion Regulation and Relations to
      Parenting Behavior.
AB  - In a diverse community sample of mothers (N = 108) and their preschool-aged
      children (Mage  = 3.50 years), this study conducted person-oriented analyses of
      maternal emotion regulation (ER) based on a multimethod assessment incorporating
      physiological, observational, and self-report indicators. A model-based cluster
      analysis was applied to five indicators of maternal ER: maternal self-report,
      observed negative affect in a parent-child interaction, baseline respiratory
      sinus arrhythmia (RSA), and RSA suppression across two laboratory tasks. Model
      based cluster analyses revealed four maternal ER profiles, including a group of
      mothers with average ER functioning, characterized by socioeconomic advantage and
      more positive parenting behavior. A dysregulated cluster demonstrated the
      greatest challenges with parenting and dyadic interactions. Two clusters of
      intermediate dysregulation were also identified. Implications for assessment and
      applications to parenting interventions are discussed.

PMID- 29034463
TI  - Statin treatment may lower the risk of postradiation epilepsy in patients with
      nasopharyngeal carcinoma.
AB  - OBJECTIVE: This study aimed to clarify the effect of statins on preventing the
      risk of postradiation epilepsy. METHODS: We performed a retrospective analysis of
      neurological nasopharyngeal carcinoma patients with a history of radiotherapy.
      Patients with a history of epilepsy before radiation and those who received
      prophylactically antiepileptic treatment were excluded. The demographic and
      clinical data of these patients were collected through chart review. We used
      Kaplan-Meier analysis (log-rank test) to examine the effect of statins on
      epilepsy-free survival. Cox regression analysis was utilized to identify
      independent predictive variables. RESULTS: Our study included 532 patients (405
      males and 127 females) with a mean follow-up of 28.1 months. During follow-up,
      471 (88.5%) patients developed radiation-induced brain necrosis (RN). Within a
      mean latency of 24.1 months, 88 (16.5%) patients experienced epilepsy, of whom 27
      (27 of 88, 30.7%) patients suffered from epilepsy before the diagnosis of RN.
      Thirty-six (36 of 88, 40.9%) cases of epilepsy occurred after RN onset, and in 22
      cases (22 of 88, 25.0%) epilepsy was the first presentation of RN. Three patients
      suffered from epilepsy but did not have RN. Eighty-eight patients in our cohort
      were treated with statins because of hyperlipidemia or prevention of
      cardiocerebrovascular diseases, of whom six (6.8%) developed epilepsy, whereas in
      those without statin, the epileptic rate was 18.5%. Log-rank test found that
      there was a significant difference in epilepsy-free survival between patients who
      used statins and those who did not (p = 0.016). After adjusting for confounding
      variables, multivariate Cox regression analysis revealed that statin use could
      still significantly reduce the risk of epilepsy after radiation (hazard ratio =
      0.36, 95% confidence interval = 0.15-0.82, p = 0.015). However, for the patients
      who already suffered from RN, statin treatment did not lower the risk of post-RN
      epilepsy. SIGNIFICANCE: Early statin use may reduce the risk of postradiotherapy
      epilepsy in patients with nasopharyngeal carcinoma.

PMID- 29034464
TI  - Stigma, Expressed Emotion, and Quality of Life in Caregivers of Individuals with
      Dementia.
AB  - Expressed emotion (EE) is a measure of a caregiver's critical and emotionally
      overinvolved (EOI; e.g., intrusive, self-sacrificing) attitudes and behaviors
      toward a person with a mental illness. Mounting evidence indicates that high
      levels of these critical and EOI attitudes and behaviors (collectively termed
      high EE) in family members are associated with a poorer course of illness for
      people with a range of disorders, including dementia (Nomura et al., 2005).
      However, less is known about factors that might trigger high EE and how high EE
      might impact dementia caregivers' own mental health. In this study we propose
      that caregivers who perceive stigma from their relative's illness may be more
      likely to be critical or intrusive (high EOI) toward their relative in an attempt
      to control symptomatic behaviors. We further hypothesized that high EE would
      partially mediate the link between stigma and quality of life (QoL) as there is
      some evidence that high EE is associated with poorer mental health in caregivers
      themselves (Safavi et al., 2015). In line with study hypotheses and using a
      sample of 106 dementia caregivers, we found that greater caregiver stigma was
      associated with both high EE (for criticism and EOI) and with poorer QoL.
      Mediational analyses further confirmed that high EE accounts for much of the
      association between stigma and poorer QoL. Study results suggest that addressing
      caregiver stigma in therapy could reduce levels of high EE and indirectly
      therefore improve caregiver QoL. Intervening directly to reduce high EE could
      also improve caregiver QoL.

PMID- 29034465
TI  - Gene expression trade-offs between defence and growth in English elm induced by
      Ophiostoma novo-ulmi.
AB  - Wilt diseases caused by vascular pathogens include some of the most damaging
      stresses affecting trees. Dutch elm disease (DED), caused by the fungus
      Ophiostoma novo-ulmi, destroyed most of North American and European elm
      populations in the 20th century. The highly susceptible English elm, also known
      as Atinian clone, suffered the highest mortality rates during the last pandemic
      event, probably due to its lack of genetic diversity. To study the DED
      pathosystem, we inoculated English elm ramets with O. novo-ulmi and evaluated
      xylem anatomy, molecular response, and disease symptoms. The high DED
      susceptibility of the clone was linked to xylem structure. The transcript levels
      changed significantly for 1,696 genes during O. novo-ulmi invasion. Genes
      covering different steps of the plant immune system were identified, many of
      which showed homology with Arabidopsis thaliana genes involved in systemic
      acquired resistance. Induction of several pathogenesis-related proteins and
      repression of fasciclin-like arabinogalactan proteins and other cell wall
      biosynthesis pathways evidence unbalanced costs between growth and defence
      mechanisms far from the inoculation point. This study sheds light on elm
      molecular defence mechanisms against DED.

PMID- 29034466
TI  - Biological observations on the broadfin shark Lamiopsis temminckii
      (Carcharhiniformes: Carcharhinidae).
AB  - Biological information was collected from 214 individuals of the broadfin shark
      Lamiopsis temminckii measuring 418 to 1782 mm total length, LT . Size at maturity
      (L50 ) for females and males was estimated at 1430 and 1368 mm LT , respectively,
      while mature and gravid females were observed from 1350 mm LT with litter sizes 2
      8 and size at birth 418-650 mm LT . Analysis of stomach contents revealed a
      variety of prey, primarily crustaceans (54.0%), teleosts (42.7%) and cephalopods.

PMID- 29034467
TI  - First insights into the function of the sawshark rostrum through examination of
      rostral tooth microwear.
AB  - Potential roles of the rostrum of sawsharks (Pristiophoridae), including
      predation and self-defence, were assessed through a variety of inferential
      methods. Comparison of microwear on the surface of the rostral teeth of sawsharks
      and sawfishes (Pristidae) show that microwear patterns are alike and suggest that
      the elongate rostra in these two elasmobranch families are used for a similar
      purpose (predation). Raman spectroscopy indicates that the rostral teeth of both
      sawsharks and sawfishes are composed of hydroxyapatite, but differ in their
      collagen content. Sawfishes possess collagen throughout their rostral teeth
      whereas collagen is present only in the centre of the rostral teeth of sawsharks,
      which may relate to differences in ecological use. The ratio of rostrum length to
      total length in the common sawshark Pristiophorus cirratus was found to be
      similar to the largetooth sawfish Pristis pristis but not the knifetooth sawfish
      Anoxypristis cuspidata. Analysis of the stomach contents of P. cirratus indicates
      that the diet consists of demersal fishes and crustaceans, with shrimp from the
      family Pandalidae being the most important dietary component. No prey item showed
      evidence of wounds inflicted by the rostral teeth. In light of the similarities
      in microwear patterns, rostral tooth chemistry and diet with sawfishes, it is
      hypothesised that sawsharks use their rostrum in a similar manner for predation
      (sensing and capturing prey) and possibly for self-defence.

PMID- 29034468
TI  - Using the common marmoset for neurophysiological studies of neocortical
      functions.

PMID- 29034469
TI  - Effect of mono-(2-ethylhexyl) phthalate (MEHP) on proliferation of and steroid
      hormone synthesis in rat ovarian granulosa cells in vitro.
AB  - This study aimed to examine the proliferation of and secretion by rat ovarian
      granulosa cells (GCs) treated with mono-(2-ethylhexyl) phthalate (MEHP). Ovarian
      GCs were incubated with MEHP at concentration of 0, 25, 50, 100, and 200 uM for
      24 hr. Cell viability was determined using the MTT Cell Proliferation Assay.
      Progesterone and estradiol production was evaluated by radioimmunoassay (RIA) and
      the expression of FSHR, PR, and ER was measured by immunocytochemistry. StAR,
      P450scc, 3beta-HSD, 17beta-HSD, and P450 arom mRNA levels were determined by RT
      PCR. MEHP markedly attenuated proliferation of GCs, increased expression of sex
      hormone receptors and key enzymes in progesterone production, and stimulated
      steroid hormone secretion. The result of these analyses demonstrates that MEHP
      exposure of GCs may have effects on rat ovarian functions.

PMID- 29034470
TI  - Involvement of the Nrf2/HO-1/CO axis and therapeutic intervention with the CO
      releasing molecule CORM-A1, in a murine model of autoimmune hepatitis.
AB  - Concanavalin A (ConA)-induced hepatitis is an experimental model of human
      autoimmune hepatitis induced in rodents by i.v. injection of Con A. The disease
      is characterized by increase in serum levels of transaminases and massive immune
      infiltration of the livers. Type 1, type 2, and type 17 cytokines play a
      pathogenic role in the development of ConA-induced hepatitis. To understand
      further the immunoregulatory mechanisms operating in the development and
      regulation of ConA-induced hepatitis, we have evaluated the role of the anti
      inflammatory pathway Nrf2/HO-1/CO (Nuclear Factor E2-related Factor 2/Heme
      Oxygenase-1/Carbon Monoxide) in this condition and determined whether the in vivo
      administration of CO via the CO-releasing molecule (CORM) CORM-A1, influences
      serological and histological development of Con-A-induced hepatitis. We have
      firstly evaluated in silico the genes belonging to the Nrf2/HO-1/CO pathway that
      are involved in the pathogenesis of autoimmune hepatitis (AIH). The data obtained
      from the in silico study demonstrate that a significant number of genes modulated
      in the liver of ConA-challenged mice belong to the Nrf2 pathway; on the other
      hand, the administration of CORM-A1 determines an improvement in several sero
      immunological and histological parameters, and it is able to modulate genes
      identified by the in silico analysis. Collectively, our data indicate that the
      Nrf2/HO-1/CO pathway is fundamental for the regulation of the immune responses,
      and that therapeutic intervention aimed at its modulation by CORM-A1 may
      represent a valuable strategy to be considered for the treatment of autoimmune
      hepatitis in humans.

PMID- 29034472
TI  - Protective effects of curcumin against aflatoxicosis: A comprehensive review.
AB  - Aflatoxicosis is a deleterious medical condition that results from aflatoxins
      (AFs) or ochratoxins (OTs). Contamination with these toxins exerts detrimental
      effects on the liver, kidneys, reproductive organs, and also on immunological and
      cardiovascular systems. Aflatoxicosis is closely associated with overproduction
      of reactive oxygen species (ROS) as key contributors to oxidative and nitrosative
      stress responses, and subsequent damages to lipids, proteins, RNA, and DNA. The
      main target organ for AF toxicity is the liver, where DNA adducts, degranulation
      of endoplasmic reticulum, increased hepatic lipid peroxide, GSH depletion,
      mitochondrial dysfunction, and reduction of enzymatic and non-enzymatic
      antioxidants are manifestations of aflatoxicosis. Curcuma longa L. (turmeric) is
      a medicinal plant widely utilized all over the world for culinary and
      phytomedical purposes. Considering the antioxidant characteristic of curcumin,
      the main active component of turmeric, this review is intended to critically
      summarize the available evidence supporting possible effectiveness of curcumin
      against aflatoxicosis. Curcumin can serve as a promising candidate for
      attenuation of the adverse consequences of aflatoxicosis, acting mainly through
      intrinsic antioxidant effects aroused from its structure, modulation of the
      immune system as reflected by interleukin-1beta and transforming growth factor
      beta, and interfering with AF's biotransformation by cytochrome P450 isoenzymes
      CYP1A, CYP3A, CYP2A, CYP2B, and CYP2C.

PMID- 29034471
TI  - Lipid signaling affects primary fibroblast collective migration and anchorage in
      response to stiffness and microtopography.
AB  - Cell migration is regulated by several mechanotransduction pathways, which
      consist of sensing and converting mechanical microenvironmental cues to internal
      biochemical cellular signals, such as protein phosphorylation and lipid
      signaling. While there has been significant progress in understanding protein
      changes in the context of mechanotransduction, lipid signaling is more difficult
      to investigate. In this study, physical cues of stiffness (10, 100, 400 kPa, and
      glass), and microrod or micropost topography were manipulated in order to
      reprogram primary fibroblasts and assess the effects of lipid signaling on the
      actin cytoskeleton. In an in vitro wound closure assay, primary cardiac
      fibroblast migration velocity was significantly higher on soft polymeric
      substrata. Modulation of PIP2 availability through neomycin treatment nearly
      doubled migration velocity on 10 kPa substrata, with significant increases on all
      stiffnesses. The distance between focal adhesions and the lamellar membrane
      (using wortmannin treatment to increase PIP2 via PI3K inhibition) was
      significantly shortest compared to untreated fibroblasts grown on the same
      surface. PIP2 localized to the leading edge of migrating fibroblasts more
      prominently in neomycin-treated cells. The membrane-bound protein, lamellipodin,
      did not vary under any condition. Additionally, fifteen micron-high micropost
      topography, which blocks migration, concentrates PIP2 near to the post. Actin
      dynamics within stress fibers, measured by fluorescence recovery after
      photobleaching, was not significantly different with stiffness, microtopography,
      nor with drug treatment. PIP2-modulating drugs delivered from microrod structures
      also affected migration velocity. Thus, manipulation of the microenvironment and
      lipid signaling regulatory drugs might be beneficial in improving therapeutics
      geared toward wound healing.

PMID- 29034473
TI  - Development and maturation of the fibrous components of the arterial roots in the
      mouse heart.
AB  - The arterial roots are important transitional regions of the heart, connecting
      the intrapericardial components of the aortic and pulmonary trunks with their
      ventricular outlets. They house the arterial (semilunar) valves and, in the case
      of the aorta, are the points of coronary arterial attachment. Moreover, because
      of the semilunar attachments of the valve leaflets, the arterial roots span the
      anatomic ventriculo-arterial junction. By virtue of this arrangement, the
      interleaflet triangles, despite being fibrous, are found on the ventricular
      aspect of the root and located within the left ventricular cavity. Malformations
      and diseases of the aortic root are common and serious. Despite the mouse being
      the animal model of choice for studying cardiac development, few studies have
      examined the structure of their arterial roots. As a consequence, our
      understanding of their formation and maturation is incomplete. We set out to
      clarify the anatomical and histological features of the mouse arterial roots,
      particularly focusing on their walls and the points of attachment of the valve
      leaflets. We then sought to determine the embryonic lineage relationships between
      these tissues, as a forerunner to understanding how they form and mature over
      time. Using histological stains and immunohistochemistry, we show that the walls
      of the mouse arterial roots show a gradual transition, with smooth muscle cells
      (SMC) forming the bulk of wall at the most distal points of attachments of the
      valve leaflets, while being entirely fibrous at their base. Although the
      interleaflet triangles lie within the ventricular chambers, we show that they are
      histologically indistinguishable from the arterial sinus walls until the end of
      gestation. Differences become apparent after birth, and are only completed by
      postnatal day 21. Using Cre-lox-based lineage tracing technology to label
      progenitor populations, we show that the SMC and fibrous tissue within the walls
      of the mature arterial roots share a common origin from the second heart field
      (SHF) and exclude trans-differentiation of myocardium as a source for the
      interleaflet triangle fibrous tissues. Moreover, we show that the attachment
      points of the leaflets to the walls, like the leaflets themselves, are derived
      from the outflow cushions, having contributions from both SHF-derived endothelial
      cells and neural crest cells. Our data thus show that the arterial roots in the
      mouse heart are similar to the features described in the human heart. They
      provide a framework for understanding complex lesions and diseases affecting the
      aortic root.

PMID- 29034474
TI  - Altered NMDA receptor-evoked intracellular Ca2+ dynamics in magnocellular
      neurosecretory neurons of hypertensive rats.
AB  - KEY POINTS: NMDA receptor (NMDAR)-mediated Ca2+ signalling plays a critical role
      in modulating hypothalamic neurosecretory function. However, whether an altered
      NMDAR-evoked changes in Ca2+ (NMDAR-DeltaCa2+ ) signalling in magnocellular
      neurosecretory cells (MNCs) may contribute to neurohumoral activation during
      disease states is unknown. We show that activation of NMDARs evoked similar
      inward currents in MNCs of sham and renovascular hypertensive (RVH) rats. Despite
      this, a prolonged and larger NMDAR-DeltaCa2+ response was observed in the latter.
      The exacerbated NMDAR-DeltaCa2+ responses in MNCs of RVH rats affected both
      somatic and dendritic compartments. Inhibition of the endoplasmic reticulum
      sarcoendoplasmic reticulum calcium trasport ATPase (SERCA) pump prolonged NMDAR
      DeltaCa2+ responses in sham rats, but not in RVH rats. Our study supports an
      altered spatiotemporal dynamic of NMDAR-DeltaCa2+ signalling in MNCs from RVH
      rats, partly due to blunted endoplasmic reticulum Ca2+ buffering capacity.
      ABSTRACT: A growing body of evidence supports an elevated NMDA receptor (NMDAR)
      mediated glutamate excitatory function in the supraoptic nucleus and
      paraventricular nucleus of hypertensive rats that contributes to neurohumoral
      activation in this disease. However, the precise mechanisms underlying altered
      NMDAR signalling in hypertension remain to be elucidated. In this study, we
      performed simultaneous electrophysiology and fast confocal Ca2+ imaging to
      determine whether altered NMDAR-mediated changes in intracellular Ca2+ levels
      (NMDAR-DeltaCa2+ ) occurred in hypothalamic magnocellular neurosecretory cells
      (MNCs) in renovascular hypertensive (RVH) rats. We found that despite evoking a
      similar excitatory inward current, activation of NMDARs resulted in a larger and
      prolonged DeltaCa2+ in MNCs from RVH rats. Changes in NMDAR-DeltaCa2+ dynamics
      were observed both in somatic and dendritic compartments. Inhibition of the
      sarcoendoplasmic reticulum calcium trasport ATPase (SERCA) pump activity with
      thapsigargin prolonged NMDAR-DeltaCa2+ responses in MNCs of sham rats, but this
      effect was occluded in RVH rats, thus equalizing the magnitude and time course of
      the NMDA-DeltaCa2+ responses between the two experimental groups. Taken together,
      our results support (1) an exacerbated NMDAR-DeltaCa2+ response in
      somatodendritic compartments of MNCs of RVH rats, and (2) that a blunted ER Ca2+
      buffering capacity contributes to the altered NMDAR-DeltaCa2+ dynamics in this
      condition. Thus, altered spatiotemporal dynamics of the NMDAR-DeltaCa2+ response
      stands as an underlying mechanism contributing to neurohumoral activation in
      neurogenic hypertension.

PMID- 29034476
TI  - Third molor extractions among Australian adults: findings from the 2013 National
      Dental Telephone Interview Survey.
AB  - OBJECTIVES: To identify, over the previous 12 months, whether: (i) dental
      insurance is associated with a higher number of third molar extractions (TME);
      (ii) single versus multiple TME is associated with self-rated oral health; and
      (iii) TME when 18-25 years of age is associated with fewer days absent from work
      because of dental problems. METHODOLOGY: Australia's 2013 National Dental
      Telephone Interview Survey, which included: socio-demographics; and number of
      extractions, reasons for extractions, self-rated oral health and days absent from
      work because of dental problems, all in the past 12 months. RESULTS: The majority
      of TME recipients were female [56.6%, standard error (SE) = 6.0%], 18-25 years of
      age (63.0%, SE = 5.4%), held a tertiary qualification (73.9%, SE = 5.4%), had a
      total annual household income of >=$60,000 (58.3%, SE = 6.4%), were dentally
      insured (52.6%, SE = 6.2%) and received multiple TME (60.9%, SE = 8.5%). Number
      of TME was associated with having dental insurance [B = 0.97: 95% confidence
      interval (95% CI): 0.5-1.5] and days of work absence because of dental problems
      (B = 1.10; 95% CI: 0.26-1.94). Receiving single TME versus multiple TME was not
      associated with self-rated oral health (B = -0.25; 95% CI: -0.76 to 0.25).
      Receiving TME when 18-25 years of age versus when older than 25 years of age was
      not associated with days absent from work because of dental problems (B = 0.48;
      95% CI: -0.37 to 2.33). CONCLUSION: Dental insurance was associated with a higher
      TME count without improving self-reported oral health in the short-term. Using
      age as a justification for prophylactic TME might be questionable because,
      receiving TME when 18-25 years of age versus when older than 25 years of age did
      not reduce days absent from work because of dental problems.

PMID- 29034475
TI  - 2D:4D digit ratio is not a biomarker of developmental programming in baboons
      (Papio hamadryas species).
AB  - We hypothesized second-to-fourth hand digit ratio (2D:4D) is a biomarker of
      developmental programming in 3 baboon groups: intrauterine growth restriction (7
      females, 8 males), exposure during fetal life to synthetic glucocorticoids (4
      females, 5 males), and controls (66 females, 20 males). 2D:4D was similar between
      sexes and groups.

PMID- 29034477
TI  - Hybrid bodies and the materiality of everyday life: how people living with
      pacemakers and defibrillators reinvent everyday routines and intimate relations.
AB  - Technologies inside bodies pose new challenges in a technological culture. For
      people with pacemakers and defibrillators, activities such as passing security
      controls at airports, using electromagnetic machines, electrical domestic
      appliances and electronic devices, and even intimate contacts with their loved
      ones can turn into events where the proper functioning of their device may be at
      risk. Anticipation of potentially harmful events and situations thus becomes an
      important part of the choreography of everyday life. Technologies inside bodies
      not only pose a challenge for patients living with these devices but also to
      theorising body-technology relations. Whereas researchers usually address the
      merging of bodies and technologies, implants ask us to do the opposite as well.
      How are we to understand human-technology relations in which technologies should
      not entangle with bodies because they serve other purposes? Based on a study of
      the daily life practices of people with pacemakers and defibrillators in the
      Netherlands and the US, I argue that disentanglement work, i.e. work involved to
      prevent entanglements with objects and people that may inflict harm upon
      implanted devices, is key to understanding how hybrid bodies can survive in
      today's densely populated technological landscape.

PMID- 29034480
TI  - Antioxidant therapy in a mouse model of Duchenne muscular dystrophy: some
      promising results but with a weighty caveat.

PMID- 29034479
TI  - Scaling of the ankle extensor muscle-tendon units and the biomechanical
      implications for bipedal hopping locomotion in the post-pouch kangaroo Macropus
      fuliginosus.
AB  - Bipedal hopping is used by macropods, including rat-kangaroos, wallabies and
      kangaroos (superfamily Macropodoidea). Interspecific scaling of the ankle
      extensor muscle-tendon units in the lower hindlimbs of these hopping bipeds shows
      that peak tendon stress increases disproportionately with body size.
      Consequently, large kangaroos store and recover more strain energy in their
      tendons, making hopping more efficient, but their tendons are at greater risk of
      rupture. This is the first intraspecific scaling analysis on the functional
      morphology of the ankle extensor muscle-tendon units (gastrocnemius, plantaris
      and flexor digitorum longus) in one of the largest extant species of hopping
      mammal, the western grey kangaroo Macropus fuliginosus (5.8-70.5 kg post-pouch
      body mass). The effective mechanical advantage of the ankle extensors does not
      vary with post-pouch body mass, scaling with an exponent not significantly
      different from 0.0. Therefore, larger kangaroos balance rotational moments around
      the ankle by generating muscle forces proportional to weight-related
      gravitational forces. Maximum force is dependent upon the physiological cross
      sectional area of the muscle, which we found scales geometrically with a mean
      exponent of only 0.67, rather than 1.0. Therefore, larger kangaroos are limited
      in their capacity to oppose large external forces around the ankle, potentially
      compromising fast or accelerative hopping. The strain energy return capacity of
      the ankle extensor tendons increases with a mean exponent of ~1.0, which is much
      shallower than the exponent derived from interspecific analyses of hopping
      mammals (~1.4-1.9). Tendon safety factor (ratio of rupture stress to estimated
      peak hopping stress) is lowest in the gastrocnemius (< 2), and it decreases with
      body mass with an exponent of -0.15, extrapolating to a predicted rupture at 160
      kg. Extinct giant kangaroos weighing 250 kg could therefore not have engaged in
      fast hopping using 'scaled-up' lower hindlimb morphology of extant western grey
      kangaroos.

PMID- 29034481
TI  - Stagewise multidimensional visual discrimination by pigeons.
AB  - We trained six pigeons in a stagewise Multiple Necessary Cues (MNC) go/no-go task
      to document the dynamics of discrimination learning involving increasingly
      complex visual stimuli. The compound stimuli were composed from four dimensions,
      each of which could assume either of two extreme values or their intermediate
      value: Shape, Size, Line Orientation, and Brightness. Starting with a stimulus
      composed entirely from intermediate values, we replaced those values with each of
      the two extreme dimensional values in four successive stages, thereby increasing
      the stimulus set from 2 in Stage 1 to 16 in Stage 4. In each stage, only one
      combination of values signaled food (S+ ), whereas the remaining combinations did
      not (S- s). We calculated the rate of pecking during the first 15 s of each
      stimulus presentation and, in any given stage, training continued until the rate
      of responding to all of the S- s was less than 20% of the rate of responding to
      the S+ . All pigeons successfully acquired the final discrimination, suggesting
      that they attended to all of the dimensions relevant for the discrimination. We
      also replicated the key results of prior MNC studies: (1) the number of extreme
      dimensional values in each stage was positively related to the amount of training
      required for pigeons to acquire the discrimination; (2) attentional tradeoffs
      were most often observed when three or four dimensions were being trained; and
      (3) throughout training, the number of dimensional values in the S- s that
      differed from the S+ was positively related to their discriminability from S+ .

PMID- 29034482
TI  - Deep reinforcement learning for automated radiation adaptation in lung cancer.
AB  - PURPOSE: To investigate deep reinforcement learning (DRL) based on historical
      treatment plans for developing automated radiation adaptation protocols for
      nonsmall cell lung cancer (NSCLC) patients that aim to maximize tumor local
      control at reduced rates of radiation pneumonitis grade 2 (RP2). METHODS: In a
      retrospective population of 114 NSCLC patients who received radiotherapy, a three
      component neural networks framework was developed for deep reinforcement learning
      (DRL) of dose fractionation adaptation. Large-scale patient characteristics
      included clinical, genetic, and imaging radiomics features in addition to tumor
      and lung dosimetric variables. First, a generative adversarial network (GAN) was
      employed to learn patient population characteristics necessary for DRL training
      from a relatively limited sample size. Second, a radiotherapy artificial
      environment (RAE) was reconstructed by a deep neural network (DNN) utilizing both
      original and synthetic data (by GAN) to estimate the transition probabilities for
      adaptation of personalized radiotherapy patients' treatment courses. Third, a
      deep Q-network (DQN) was applied to the RAE for choosing the optimal dose in a
      response-adapted treatment setting. This multicomponent reinforcement learning
      approach was benchmarked against real clinical decisions that were applied in an
      adaptive dose escalation clinical protocol. In which, 34 patients were treated
      based on avid PET signal in the tumor and constrained by a 17.2% normal tissue
      complication probability (NTCP) limit for RP2. The uncomplicated cure probability
      (P+) was used as a baseline reward function in the DRL. RESULTS: Taking our
      adaptive dose escalation protocol as a blueprint for the proposed DRL (GAN + RAE
      + DQN) architecture, we obtained an automated dose adaptation estimate for use at
      ~2/3 of the way into the radiotherapy treatment course. By letting the DQN
      component freely control the estimated adaptive dose per fraction (ranging from 1
      5 Gy), the DRL automatically favored dose escalation/de-escalation between 1.5
      and 3.8 Gy, a range similar to that used in the clinical protocol. The same DQN
      yielded two patterns of dose escalation for the 34 test patients, but with
      different reward variants. First, using the baseline P+ reward function,
      individual adaptive fraction doses of the DQN had similar tendencies to the
      clinical data with an RMSE = 0.76 Gy; but adaptations suggested by the DQN were
      generally lower in magnitude (less aggressive). Second, by adjusting the P+
      reward function with higher emphasis on mitigating local failure, better matching
      of doses between the DQN and the clinical protocol was achieved with an RMSE =
      0.5 Gy. Moreover, the decisions selected by the DQN seemed to have better
      concordance with patients eventual outcomes. In comparison, the traditional
      temporal difference (TD) algorithm for reinforcement learning yielded an RMSE =
      3.3 Gy due to numerical instabilities and lack of sufficient learning.
      CONCLUSION: We demonstrated that automated dose adaptation by DRL is a feasible
      and a promising approach for achieving similar results to those chosen by
      clinicians. The process may require customization of the reward function if
      individual cases were to be considered. However, development of this framework
      into a fully credible autonomous system for clinical decision support would
      require further validation on larger multi-institutional datasets.

PMID- 29034485
TI  - Decision theory for comparing institutions.
AB  - Various forms of performance assessment are applied to public service
      institutions, such as hospitals, schools, police units, and local authorities.
      Difficulties arise in the interpretation of the results presented in some
      established formats because they require a good understanding and appreciation of
      the uncertainties involved. Usually the results have to be adapted to the
      perspectives of the users-managers of the assessed units, a consumer, or a
      central authority (a watchdog) that dispenses awards and sanctions. We present a
      decision-theoretical approach to these and related problems in which the
      perspectives are integrated in the analysis and its results are choices from a
      finite list of options (alternative courses of action).

PMID- 29034483
TI  - Effect of sensory and motor connectivity on hand function in pediatric
      hemiplegia.
AB  - OBJECTIVE: We tested the hypothesis that somatosensory system injury would more
      strongly affect movement than motor system injury in children with unilateral
      cerebral palsy (USCP). This hypothesis was based on how somatosensory and
      corticospinal circuits adapt to injury during development; whereas the motor
      system can maintain connections to the impaired hand from the uninjured
      hemisphere, this does not occur in the somatosensory system. As a corollary,
      cortical injury strongly impairs sensory function, so we hypothesized that
      cortical lesions would impair hand function more than subcortical lesions.
      METHODS: Twenty-four children with unilateral cerebral palsy had physiological
      and anatomical measures of the motor and somatosensory systems and lesion
      classification. Motor physiology was performed with transcranial magnetic
      stimulation and somatosensory physiology with vibration-evoked
      electroencephalographic potentials. Tractography of the corticospinal tract and
      the medial lemniscus was performed with diffusion tensor imaging, and lesions
      were classified by magnetic resonance imaging. Anatomical and physiological
      results were correlated with measures of hand function using 2 independent
      statistical methods. RESULTS: Children with disruptions in the somatosensory
      connectivity and cortical lesions had the most severe upper extremity
      impairments, particularly somatosensory function. Motor system connectivity was
      significantly correlated with bimanual function, but not unimanual function or
      somatosensory function. INTERPRETATION: Both sensory and motor connectivity
      impact hand function in children with USCP. Somatosensory connectivity could be
      an important target for recovery of hand function in children with USCP. Ann
      Neurol 2017;82:766-780.

PMID- 29034484
TI  - Dissecting gene-environment interactions: A penalized robust approach accounting
      for hierarchical structures.
AB  - Identification of gene-environment (G * E) interactions associated with disease
      phenotypes has posed a great challenge in high-throughput cancer studies. The
      existing marginal identification methods have suffered from not being able to
      accommodate the joint effects of a large number of genetic variants, while some
      of the joint-effect methods have been limited by failing to respect the "main
      effects, interactions" hierarchy, by ignoring data contamination, and by using
      inefficient selection techniques under complex structural sparsity. In this
      article, we develop an effective penalization approach to identify important G *
      E interactions and main effects, which can account for the hierarchical
      structures of the 2 types of effects. Possible data contamination is accommodated
      by adopting the least absolute deviation loss function. The advantage of the
      proposed approach over the alternatives is convincingly demonstrated in both
      simulation and a case study on lung cancer prognosis with gene expression
      measurements and clinical covariates under the accelerated failure time model.

PMID- 29034486
TI  - 'Everyone assumes a man to be quite strong': Men, masculinity and rheumatoid
      arthritis: A case-study approach.
AB  - Current literature has overlooked the impact of chronic illness on masculine
      identity. We therefore aimed to investigate the impact of rheumatoid arthritis (a
      long term condition, affecting more women than men) on masculine identity. Six
      focus groups with 22 men with rheumatoid arthritis (RA) (data reported elsewhere)
      followed by five one-to-one interviews with men (English, mean age: 59 years)
      sampled to reflect a heterogeneous experience of life with RA based on knowledge
      gained from the focus groups. Transcripts were analysed using thematic analysis
      and are presented as individual case studies. Whilst the case studies provide
      five distinct experiences, common themes can be drawn across them, such as the
      importance of paid work. The men needed to renegotiate their masculine identity
      to deal with their RA. Two dealt with this by pushing through pain to retain
      masculine activities, two replaced masculine roles they could no longer do with
      other roles, and one rejected masculinity completely. Men with long term
      conditions may need to re-write their masculinity scripts to enable them to
      accept and adapt to their condition. However, some men struggle with this, which
      should be taken into consideration when designing self-management services for
      men with long term conditions.

PMID- 29034487
TI  - The role of spontaneous neurotransmission in synapse and circuit development.
AB  - In the past, the spontaneous release of neurotransmitter from presynaptic
      terminals has been thought of as a side effect of evoked release, with little
      functional significance. As our understanding of the process of spontaneous
      release has increased over time, this notion has gradually changed. In this
      review, we focus on the importance of this form of release during neuronal
      development, a time of extreme levels of plasticity that includes the growth of
      dendrites and axons as well as the formation of new synaptic contacts. This
      period also encompasses high levels of neurotransmitter release from growing
      axons, and recent studies have found that spontaneous transmitter release plays
      an important role in shaping neuronal morphology as well as modulating the
      properties of newly forming synaptic contacts in the brain. Here, we bring
      together the latest findings across different species to argue that the
      spontaneous release of neurotransmitter is an important player in the wiring of
      the brain during development.

PMID- 29034488
TI  - Exploiting whole genome sequence data to fine map and characterize candidate
      genes within a quantitative trait loci region affecting androstenone on porcine
      chromosome 5.
AB  - Male piglets are routinely castrated to eliminate boar taint. However, this
      treatment is undesirable, and alternative approaches, including genetic
      strategies to reduce boar taint, are demanded. Androstenone is one of the
      causative agents of boar taint, and a QTL region affecting this pheromone has
      previously been reported on SSC5: 22.6-24.8 Mb in Duroc. The QTL region is one of
      the few reported for androstenone that does not simultaneously affect levels of
      other sex steroids. The main objective of this study was to fine map this QTL.
      Whole genome sequence data from 23 Norwegian Duroc boars were analyzed to detect
      new polymorphisms within the QTL region. A subset of 161 SNPs was genotyped in
      834 Duroc sires and analyzed for association with androstenone in adipose tissue
      and testosterone, estrone sulphate and 17beta-estradiol in blood plasma. Our
      results revealed 100 SNPs significantly associated with androstenone levels in
      fat (P < 0.001) with 94 of the SNPs being in strong linkage disequilibrium in the
      region 23.03-24.27 Mb. This haplotype block contains at least four positional
      candidate genes (HSD17B6, SDR9C7, RDH16 and STAT6) involved in androstenone
      biosynthesis. No significant associations were found between any of the SNPs and
      levels of testosterone and estrogens, confirming previous findings. The amount of
      phenotypic variance explained by single SNPs within the haplotype block was as
      high as 5.4%. As the SNPs in this region significantly affect levels of
      androstenone without affecting levels of other sex steroids, they are especially
      interesting as genetic markers for selection against boar taint.

PMID- 29034489
TI  - Modification of Automatic Alcohol-Approach Tendencies in Alcohol-Dependent
      Patients with Mild or Major Neurocognitive Disorder.
AB  - BACKGROUND: To examine the applicability of an alcohol-avoidance training
      procedure in patients with alcohol dependence and alcohol-induced neurocognitive
      disorders (NDs), we trained 2 groups that differed in the degree of cognitive
      impairment: One group fulfilled the DSM-5 criteria for alcohol-induced mild ND,
      and 1 group was diagnosed with Korsakoff's syndrome (KS) (alcohol-induced major
      ND, confabulatory/amnesic subtype; DSM-5). The intervention is assumed to match
      the preserved cognitive capacity for implicit learning in both groups. METHODS:
      Fifty-one inpatients with a mild ND and 54 inpatients with KS were trained. Six
      training sessions (including pre- and posttests) of a computerized implicit
      alcohol approach-avoidance task were applied. Neurocognitive variables were
      available from the standard assessment procedure of the clinic. RESULTS: Training
      of alcohol-avoidance tendencies is feasible in a population with alcohol-related
      NDs. The alcohol-approach bias decreased for both groups in each session. Better
      learning results over time were obtained in participants with a larger baseline
      alcohol-approach tendency. Learning effects were positively related to age and
      implicit (nondeclarative) memory functioning. No relation between training
      effects and executive or explicit memory functions was found. CONCLUSIONS:
      Training of an alcohol-avoidance tendency can be successfully applied in patients
      with alcohol dependence including those with alcohol-induced NDs.

PMID- 29034490
TI  - Hepatic Complications of Umbilical Venous Catheters in the Neonatal Period: The
      Ultrasound Spectrum.
AB  - OBJECTIVES: Umbilical venous catheterization is commonly used in the neonatal
      period; however, it has some complications. In this study, we evaluated neonates
      who underwent umbilical venous catheterization and developed hepatic
      complications. Furthermore, we aimed to define all of the possible lesions and to
      clarify the imaging findings of umbilical venous catheter-induced hepatic injury.
      METHODS: Two hundred forty-four neonates who underwent umbilical venous
      catheterization between March 2013 and September 2015 in a single tertiary care
      referral center were included in this study. To determine whether they had any
      hepatic complications, all patients underwent abdominal grayscale and Doppler
      ultrasound examinations, and their clinical data were recorded. RESULTS: The
      frequency of liver-related complications from umbilical venous catheterization
      was 33.6% (82 of 244). Air in the portal venous system was the most frequent
      complication (20.1% [49 of 244]). Left portal venous thrombosis was noted in 6.1%
      (15 of 244). Parenchymal lesions in the liver related to umbilical venous
      catheterization were seen in 7.4% of patients (18 of 244) as follows: single
      nodular echogenic lesions (4.1% [10 of 244]), branching small nodular echogenic
      lesions (2.1% [5 of 244]), and large irregular heterogeneous lesions with
      laceration and perihepatic fluid (1.2% [3 of 244]). There was no statistical
      significance for any type of complication according to the gestational age (P >
      .05). CONCLUSIONS: Hepatic complications due to umbilical venous catheters are
      not uncommon in the neonatal period. Ultrasound is the best imaging modality for
      confirming the diagnosis and for follow-up.

PMID- 29034491
TI  - Oral tofacitinib: a promising treatment in atopic dermatitis, alopecia areata and
      vitiligo.

PMID- 29034492
TI  - Transcriptome analyses reveal genes and pathways associated with fatty acid
      composition traits in pigs.
AB  - Fatty acid composition is associated with meat quality in pigs as well as with
      obesity- and diabetes-related traits in humans. Liver and muscle are important
      tissues for fatty acid metabolism. In this study, we evaluated correlations
      between liver and muscle transcriptomes and fatty acid composition traits in
      muscle and abdominal fat tissues in 335 F2 pigs from a White Duroc * Erhualian F2
      pig resource population. Transcripts significantly correlated with fatty acid
      composition traits were enriched for genes involved in the categories of
      triglyceride catabolic process, mitochondrial function, hematological and immune
      system, and disease such as Type II diabetes. Gene co-expression network analysis
      further identified liver network modules relevant to fatty acid unsaturation
      index that were enriched in platelet activation and the type I interferon
      signaling pathway and highlighted the connections between variations in fatty
      acid composition and genes involved in hematological and immune system.
      Integrative analysis of the expression QTL identified ELOVL6 and SCD as plausible
      candidate genes underlying the loci for muscle C18:1n-9/C16:1n-7 values on
      chromosome 8 and the loci for muscle C18:1n-9/C18:0 contents on chromosome 14
      respectively.

PMID- 29034493
TI  - Incidence and risk factors of surgical site infection and septic arthritis after
      elective arthroscopy in horses.
AB  - OBJECTIVE: To determine the incidence of infection and associated risk factors,
      after elective arthroscopy. STUDY DESIGN: Retrospective case study. ANIMALS:
      Horses (n=1079) undergoing elective arthroscopy. METHODS: Medical records of all
      horses that underwent elective arthroscopy between 2006 and 2013 were reviewed.
      Age, gender, breed, surgeon, number of joints operated, total anesthetic time,
      perioperative antimicrobial administration, and the presence and size of
      osteochondral fragments/subchondral lesions were recorded. For each operated
      joint, the development of postoperative infection (surgical site infection [SSI]
      and/or septic arthritis) and long-term outcome (>6 months) were recorded.
      Multivariate logistic regression was used to test for association between the
      independent variables and the dependent outcomes. RESULTS: A total of 1741 joints
      in 1079 horses underwent arthroscopy. SSI without septic arthritis occurred in 1
      fetlock joint (0.14%), 1 tibiotarsal joint (0.19%), and 6 femoropatellar joints
      (1.67%). Thirteen joints (0.75%) were diagnosed with septic arthritis, including
      1 fetlock joint (0.14%), 4 tibiotarsal joints (0.74%), and 8 femoropatellar
      joints (2.23%). The probability of postoperative SSI was higher when large
      lesions (>40 mm long) were treated, compared to medium (20-40 mm, P = .005) and
      small (<20 mm, P < .001) lesions. SSI was a significant risk factor for the
      development of septic arthritis (P < .001). Although age did not affect the
      incidence of SSI, increasing age was associated with a lower rate of septic
      arthritis rate (P = .028). CONCLUSION: Septic arthritis after elective
      arthroscopy was more likely in the presence of SSI and younger age. Horses with
      large lesions were at risk for SSI, which translated into a higher incidence of
      postoperative septic arthritis after femoropatellar arthroscopy.

PMID- 29034494
TI  - A mechanistic nonlinear model for censored and mismeasured covariates in
      longitudinal models, with application in AIDS studies.
AB  - When modeling longitudinal data, the true values of time-varying covariates may
      be unknown because of detection-limit censoring or measurement error. A common
      approach in the literature is to empirically model the covariate process based on
      observed data and then predict the censored values or mismeasured values based on
      this empirical model. Such an empirical model can be misleading, especially for
      censored values since the (unobserved) censored values may behave very
      differently than observed values due to the underlying data-generation mechanisms
      or disease status. In this paper, we propose a mechanistic nonlinear covariate
      model based on the underlying data-generation mechanisms to address censored
      values and mismeasured values. Such a mechanistic model is based on solid
      scientific or biological arguments, so the predicted censored or mismeasured
      values are more reasonable. We use a Monte Carlo EM algorithm for likelihood
      inference and apply the methods to an AIDS dataset, where viral load is censored
      by a lower detection limit. Simulation results confirm that the proposed models
      and methods offer substantial advantages over existing empirical covariate models
      for censored and mismeasured covariates.

PMID- 29034495
TI  - Melanoma arising from a plaque-type blue naevus with subcutaneous cellular
      nodules of the scalp.
AB  - Plaque-type blue naevus (PTBN) is a very rare variant of blue naevus (BN). The
      potential malignancy of subcutaneous cellular nodules (SCN) in PTBN was
      discovered in 2012, and there is currently no clear consensus on prognostic
      factors or management guidelines of such lesions. PTBN on the scalp have not been
      described in the literature. We report the clinical, histopathological and
      immunohistological features of a 50-year-old man who presented with a 30-year
      history of scalp PTBN, with malignant proliferation of nodular elements and fatal
      outcome 8 years later. This case suggests that long-term monitoring of patients
      with PTBN is required. Early surgical removal of such lesions should be
      considered, especially in the presence of any case of enlargement or change.

PMID- 29034497
TI  - Response to "Hypertrophic Cardiomyopathy in Youth Athletes: Successful Screening
      With Point-of-Care Ultrasound by Medical Students".

PMID- 29034496
TI  - Clinical Impact of the Microembolic Signal Burden During Catheter Ablation for
      Atrial Fibrillation: Just a Lot of Noise?
AB  - OBJECTIVES: Microembolic signal detection by transcranial Doppler ultrasonography
      may be considered a surrogate for cerebral events during invasive cardiac
      procedures. However, the impact of the microembolic signal count during pulmonary
      vein isolation on the clinical outcome is not well evaluated. We investigated the
      effect of the microembolic signal count on the occurrence of new silent cerebral
      embolism measured by diffusion-weighted imaging (DWI)-magnetic resonance imaging
      (MRI), changes in neuropsychological testing, and the occurrence of clinical
      events during long-term follow-up after pulmonary vein isolation. METHODS:
      Pulmonary vein isolation was performed in 41 patients. The total microembolic
      signal burden (classified into "solid," "gaseous," and "equivocal") and sustained
      thromboembolic showers of greater than 30 seconds were recorded. Diffusion
      weighted imaging-MRI and neuropsychological testing were performed before and
      after pulmonary vein isolation to assess for silent cerebral embolism and
      neuropsychological sequelae. Long-term follow-up was performed by telephone to
      assess for stroke/transient ischemic attack. RESULTS: A total of 68,729
      microembolic signals (14,893 solid, 11,909 gaseous, and 41,927 equivocal) with an
      average of 1676 signals per patient and 42 thromboembolic showers were recorded.
      No correlation between the microembolic signal/thromboembolic shower count and
      the occurrence of new DWI lesions or neuropsychological capability was found.
      After a mean follow-up +/- SD of 49 +/- 4 months, 1 patient had an overt
      transient ischemic event, which was not associated with a high microembolic
      signal count. CONCLUSIONS: In this multicenter study, we found no impact of the
      intraprocedural microembolic symbol/thromboembolic shower count on the occurrence
      of new DWI lesions, neuropsychological capability, or overt neurologic deficits
      after pulmonary vein isolation. Thus, not only the microembolic signal count but
      also procedural/individual factors may contribute to commensurable clinical
      damage, which may challenge this method as a valid biomarker during pulmonary
      vein isolation.

PMID- 29034498
TI  - Design, Synthesis, and Screening of Triazolopyrimidine-Pyrazole Hybrids as Potent
      Apoptotic Inducers.
AB  - An efficient synthesis of novel 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-5,7-dimethyl
      [1,2,4]triazolo[4,3-a]-pyrimidines was accomplished by the oxidation of
      pyrimidinylhydrazones by using organoiodine(III) reagent. All new
      triazolopyrimidine derivatives bearing the pyrazole scaffold were screened to
      evaluate them as a reproductive toxicant in the testicular germ cells of goat
      (Capra hircus). This study aimed at assessing the cytological and biochemical
      changes in testicular germ cells after the exposure to triazolopyrimidines in a
      dose- and time-dependent manner. Histomorphological analysis, fluorescence
      assays, apoptosis quantification, and terminal deoxynucleotidyl transferase dUTP
      mediated nick-end labeling (TUNEL) assays were performed to determine cytological
      changes, whereas thiobarbituric acid-reactive substance (TBARS) and ferric
      reducing antioxidant power (FRAP) assays were carried out to measure the
      oxidative stress in triazolopyrimidines treated germ cells. The parallel use of
      these methods enabled us to determine the role of triazolopyrimidines in inducing
      apoptosis as a consequence of cytogenetic damage and oxidative stress generated
      in testicular germ cells of goat.

PMID- 29034499
TI  - Early interaction in autism spectrum disorder: Mothers' and children's behaviours
      during joint engagement.
AB  - BACKGROUND: More knowledge about the interaction between young children with
      autism spectrum disorder and their parents is one way to improve intervention.
      This study aims to investigate the behaviours of mothers and children with autism
      spectrum disorder during joint engagement, with a focus on pacing or rate (i.e.,
      incidences per minute) of their behaviours when being in this state. METHOD:
      Video recordings of 10 min of free-play between 58 children (2-4 years) diagnosed
      with childhood autism and their mothers were used to examine rate of mothers' and
      children's behaviours (i.e., toy introduction, toy expansion, positive affect,
      and language) during joint engagement, the association between rate of mothers
      and children's behaviours, the relation between rate of mothers' behaviours and
      time in joint engagement, and how child factors might be associated with the
      latter. RESULTS: Mothers(m) and children(c) showed similar rate of positive
      affect (Mm  = 0.6/Mc  = 0.5) and toy expansion (Mm  = 0.7/Mc  = 0.7) per minute,
      whereas mothers talked almost three times more than their children (Mm  = 10.2/Mc
      = 3.8). In contrast, mothers introduced fewer toys compared to the children (Mm 
      = 0.7/Mc  = 1.2). Rate of mothers' toy introduction, toy expansion, and positive
      affect was inversely related to time in joint engagement (Regression coefficient
      = -70.7 to -48.5, p = .006 to .024). Rates of mothers' and children's behaviours
      were associated (Spearman rank order coefficient = .53 to .29, p < .001 to .03),
      but neither rate of children's behaviours nor mental age was associated with the
      observed relation between rate of these maternal behaviours and time in joint
      engagement. CONCLUSION: Time in joint engagement was related to rate of mothers'
      behaviours and children's mental age but not to rate of children's behaviours in
      this study. Thus, intervention teaching parents of young children with autism
      strategies designed to increase time in joint engagement may be vital. The
      complex nature of the interaction between mother and child behaviours in
      promoting joint engagement warrants further elucidation.

PMID- 29034500
TI  - How Communication Between Nucleosomes Enables Spreading and Epigenetic Memory of
      Histone Modifications.
AB  - Nucleosomes "talk" to each other about their modification state to form extended
      domains of modified histones independently of the underlying DNA sequence. At the
      same time, DNA elements promote modification of nucleosomes in their vicinity.
      How do these site-specific and histone-based activities act together to regulate
      spreading of histone modifications along the genome? How do they enable
      epigenetic memory to preserve cell identity? Many models for the dynamics of
      repressive histone modifications emphasize the role of strong positive feedback
      loops, which reinforce histone modifications by recruiting histone modifiers to
      preexisting modifications. Recent experiments question that repressive histone
      modifications are self-sustained independently of their genomic context, thereby
      indicating that histone-based feedback is relatively weak. In the present review,
      current models for the dynamics of histone modifications are compared and it is
      suggested that limitation of histone-based feedback is key to intrinsic
      confinement of spreading and coexistence of short- and long-term memory at
      different genomic loci. See also the video abstract here:
      https://youtu.be/3bxr_xDEZfQ.

PMID- 29034501
TI  - Influence of dental materials on cells of the equine periodontium.
AB  - BACKGROUND: Therapy for equine periodontal disease can include filling of the
      periodontal pockets and widened interproximal spaces. Recommended dental
      materials are generally adopted from human dentistry. OBJECTIVES: To evaluate the
      biocompatibility of dental materials for equine periodontal fillings in vitro.
      STUDY DESIGN: In vitro experiments. METHODS: Four different dental materials
      (PeriCare(r) , Provicol(r) , Calxyl(r) and Honigum) were tested on equine
      periodontal fibroblasts. Possible cytotoxic effects were assessed microscopically
      and by MTT assay, and the expression of inflammatory marker genes was measured by
      qRT-PCR. RESULTS: PeriCare(r) and Provicol(r) had no effects on the cells,
      whereas Honigum and Calxyl(r) were associated with severe cytotoxic effects. MAIN
      LIMITATIONS: The results of this in vitro study need to be confirmed by clinical
      studies. CONCLUSIONS: Before adapting dental materials from human dentistry, it
      is crucial to initially test them in a specific equine model.

PMID- 29034502
TI  - Ghost reduction in echo-planar imaging by joint reconstruction of images and line
      to-line delays and phase errors.
AB  - PURPOSE: To correct line-to-line delays and phase errors in echo-planar imaging
      (EPI). THEORY AND METHODS: EPI-trajectory auto-corrected image reconstruction
      (EPI-TrACR) is an iterative maximum-likelihood technique that exploits data
      redundancy provided by multiple receive coils between nearby lines of k-space to
      determine and correct line-to-line trajectory delays and phase errors that cause
      ghosting artifacts. EPI-TrACR was efficiently implemented using a segmented FFT
      and was applied to in vivo brain data acquired at 7 T across acceleration (1*-4*)
      and multishot factors (1-4 shots), and in a time series. RESULTS: EPI-TrACR
      reduced ghosting across all acceleration factors and multishot factors, compared
      to conventional calibrated reconstructions and the PAGE method. It also achieved
      consistently lower ghosting in the time series. Averaged over all cases, EPI
      TrACR reduced root-mean-square ghosted signal outside the brain by 27% compared
      to calibrated reconstruction, and by 40% compared to PAGE. CONCLUSION: EPI-TrACR
      automatically corrects line-to-line delays and phase errors in multishot,
      accelerated, and dynamic EPI. While the method benefits from additional
      calibration data for initialization, it was not a requirement for most
      reconstructions. Magn Reson Med 79:3114-3121, 2018. (c) 2017 International
      Society for Magnetic Resonance in Medicine.

PMID- 29034503
TI  - Detection of a new heterozygous germline ETV6 mutation in a case with
      hyperdiploid acute lymphoblastic leukemia.
AB  - ETV6 is a target of recurrent aberrations in sporadic and familial acute
      lymphoblastic leukemia (ALL). Here, we report on a new pedigree with a germline
      ETV6 mutation in which the index patient and his father developed high
      hyperdiploid (HeH) ALL and polycythemia vera at age 13 and 51, respectively. The
      index patient achieved durable complete remission without transplantation but had
      persistent moderate thrombocytopenia without bleeding tendency. To determine the
      prevalence of ETV6 alterations in HeH-ALL, we screened 81 unrelated subjects with
      HeH-ALL by single nucleotide polymorphism array and high-throughput sequencing
      for the ETV6 gene. Overall, ETV6 microdeletions and mutations were identified in
      9% of cases, all of which were somatic and considered as secondary events. Apart
      from the index patient, no germline ETV6 aberration was identified. Finally, we
      reviewed the literature for ETV6 germline aberrations and predispositions to ALL.

PMID- 29034504
TI  - Revising the paradigm for jail diversion for people with mental and substance use
      disorders: Intercept 0.
AB  - A conceptual model for community-based strategic planning to address the
      criminalization of adults with mental and substance use disorders, the Sequential
      Intercept Model has provided jurisdictions with a framework that overcomes
      traditional boundaries between the agencies within the criminal justice and
      behavioral health systems. This article presents a new paradigm, Intercept 0, for
      expanding the utility of the Sequential Intercept Model at the front end of the
      criminal justice system. Intercept 0 encompasses the early intervention points
      for people with mental and substance use disorders before they are placed under
      arrest by law enforcement. The addition of Intercept 0 creates a conceptual space
      that enables stakeholders from the mental health, substance use, and criminal
      justice systems to consider the full spectrum of real-world interactions
      experienced by people with mental and substance use disorders with regard to
      their trajectories, or lack thereof, through the criminal justice system.

PMID- 29034505
TI  - In vivo characterization of the downfield part of 1 H MR spectra of human brain
      at 9.4 T: Magnetization exchange with water and relation to conventionally
      determined metabolite content.
AB  - PURPOSE: To perform exchange-rate measurements on the in vivo human brain
      downfield spectrum (5-10 ppm) at 9.4 T and to compare the variation in
      concentrations of the downfield resonances and of known upfield metabolites to
      determine potential peak labels. METHODS: Non-water-suppressed metabolite cycling
      was used in combination with an inversion transfer technique in two brain
      locations in healthy volunteers to measure the exchange rates and T1 values of
      exchanging peaks. Spectra were fitted with a heuristic model of a series of 13 or
      14 Voigt lines, and a Bloch-McConnell model was used to fit the exchange rate
      curves. Concentrations from non-water-inverted spectra upfield and downfield were
      compared. RESULTS: Mean T1 values ranged from 0.40 to 0.77 s, and exchange rates
      from 0.74 to 13.8 s-1 . There were no significant correlations between downfield
      and upfield concentrations, except for N-acetylaspartate, with a correlation
      coefficient of 0.63 and P < 0.01. CONCLUSIONS: Using ultrahigh field allowed
      improved separation of peaks in the 8.2 to 8.5 ppm amide proton region, and the
      exchange rates of multiple downfield resonances including the 5.8-ppm peak,
      previously tentatively assigned to urea, were measured in vivo in human brain.
      Downfield peaks consisted of overlapping components, and largely missing
      correlations between upfield and downfield resonances-although not conclusive
      indicate limited contributions from metabolites present upfield to the downfield
      spectrum. Magn Reson Med 79:2863-2873, 2018. (c) 2017 International Society for
      Magnetic Resonance in Medicine.

PMID- 29034506
TI  - Microglial-induced Muller cell gliosis is attenuated by progesterone in a mouse
      model of retinitis pigmentosa.
AB  - Norgestrel, a progesterone analogue, has demonstrated neuroprotective effects in
      a mouse model of retinitis pigmentosa. Neuroprotection is achieved in part
      through Norgestrels anti-inflammatory properties, alleviating detrimental
      microglial activity. Gliosis is a feature of many neurodegenerative diseases of
      the retina, including retinitis pigmentosa. Muller glia, a type of macroglia
      found in the retina, are major contributors of gliosis, characterized by the
      upregulation of glial fibrillary acidic protein (GFAP). Microglia-Muller glia
      crosstalk has been implicated in the initiation of gliosis. In the rd10 retina,
      increased microglial activity and gliotic events are observed prior to the onset
      of photoreceptor loss. We hypothesized that Norgestrels dampening effects on
      harmful microglial activity would consequently impact on gliosis. In the current
      study, we explore the role of microglia-Muller glia crosstalk in degeneration and
      Norgestrel-mediated neuroprotection in the rd10 retina. Norgestrels
      neuroprotective effects in the rd10 retina coincide with significant decreases in
      both microglial activity and Muller cell gliosis. Using a Muller glial cell line,
      rMC-1, and isolated microglia, we show that rd10 microglia stimulate GFAP
      production in rMC-1 cells. Norgestrel attenuates gliosis through direct actions
      on both microglia and Muller glia. Norgestrel reduces the release of harmful
      stimuli from microglia, such as interferon-gamma, which might otherwise signal to
      Muller glia and stimulate gliosis. We propose that Norgestrel also targets Muller
      cell gliosis directly, by limiting the availability of pSTAT3, a known
      transcription factor for GFAP. These findings highlight an important aspect to
      Norgestrels neuroprotective effects in the diseased retina, in combating Muller
      cell gliosis.

PMID- 29034507
TI  - Screening for Sturge-Weber syndrome: A state-of-the-art review.
AB  - Infants with a high-risk distribution of port-wine stains are commonly screened
      for Sturge-Weber syndrome using brain magnetic resonance imaging. There is no
      consensus about which port-wine stain phenotypes to screen, optimal timing,
      screening sensitivity, or whether presymptomatic diagnosis improves
      neurodevelopmental outcomes. This state-of-the-art review examines the evidence
      in favor of screening for Sturge-Weber syndrome, based on its effect on
      neurodevelopmental outcomes, against the risks and limitations of screening
      magnetic resonance imaging and electroencephalography. A literature search of
      PubMed/MEDLINE was conducted between January 2005 and May 2017 using key search
      terms. Relevant articles published in English were reviewed; 34 articles meeting
      the search criteria were analyzed according to the following outcome measures:
      neurodevelopmental outcome benefit of screening, diagnostic yield, financial
      costs, procedural risks, and limitations of screening magnetic resonance imaging
      and electroencephalography. There is no evidence that a presymptomatic Sturge
      Weber syndrome diagnosis with magnetic resonance imaging results in better
      neurodevelopmental outcomes. The utility of electroencephalographic screening is
      also unestablished. In Sturge-Weber syndrome, neurodevelopmental outcomes depend
      on prompt recognition of neurologic red flags and early seizure control. Small
      numbers and a lack of prospective randomized controlled trials limit these
      findings. For infants with port-wine stain involving skin derived from the
      frontonasal placode (forehead and hemifacial phenotypes), we recommend early
      referral to a pediatric neurologist for parental education, counselling, and
      monitoring for neurologic red flags and seizures and consideration of
      electroencephalography regardless of whether magnetic resonance imaging is
      performed or its findings.

PMID- 29034510
TI  - Youth Program Adult Leader's Directive Assistance and Autonomy Support and
      Development of Adolescents' Agency Capacity.
AB  - Developing a capacity for exercising agency is an important developmental task of
      adolescence. Many organized youth programs provide adolescents opportunities to
      build their capacity to exercise agency. The researchers tested hypotheses that
      adult youth program leader's directive assistance and autonomy support would
      promote adolescents' capacity for agency. They surveyed 441 high school
      adolescents and 11 adult advisors from 10 Future Farmers of America chapters
      twice over 2 years. Adolescents self-reported on their capacity for agency and
      advisors reported on each adolescent's capacity. Directive assistance and
      autonomy support correlated with the capacity for agency within both time points.
      Only autonomy support predicted adolescents' capacity for agency over time.
      Implications of leader's support for adolescents' capacity for exercising agency
      are discussed.

PMID- 29034508
TI  - Ulk4 deficiency leads to hypomyelination in mice.
AB  - Brain nerve fibers are insulated by myelin which is produced by oligodendrocytes.
      Defects in myelination are increasingly recognized as a common pathology
      underlying neuropsychiatric and neurodevelopmental disorders, which are
      associated with deletions of the Unc-51-like kinase 4 (ULK4) gene. Key
      transcription factors have been identified for oligodendrogenesis, but little is
      known about their associated regulators. Here we report that Ulk4 acts as a key
      regulator of myelination. Myelination is reduced by half in the Ulk4tm1a/tm1a
      hypomorph brain, whereas expression of axonal marker genes Tubb3, Nefh, Nefl and
      Nefm remains unaltered. Transcriptome analyses reveal that 8 (Gfap, Mbp, Mobp,
      Plp1, Slc1a2, Ttr, Cnp, Scd2) of the 10 most significantly altered genes in the
      Ulk4tm1a/tm1a brain are myelination-related. Ulk4 is co-expressed in Olig2+ (pan
      oligodendrocyte marker) and CC1+ (mature myelinated oligodendrocyte marker) cells
      during postnatal development. Major oligodendrogeneic transcription factors,
      including Olig2, Olig1, Myrf, Sox10, Sox8, Sox6, Sox17, Nkx2-2, Nkx6-2 and
      Carhsp1, are significantly downregulated in the mutants. mRNA transcripts
      enriched in oligodendrocyte progenitor cells (OPCs), the newly formed
      oligodendrocytes (NFOs) and myelinating oligodendrocytes (MOs), are significantly
      attenuated. Expression of stage-specific oligodendrocyte factors including Cspg4,
      Sox17, Nfasc, Enpp6, Sirt2, Cnp, Plp1, Mbp, Ugt8, Mag and Mog are markedly
      decreased. Indirect effects of axon caliber and neuroinflammation may also
      contribute to the hypomyelination, as Ulk4 mutants display smaller axons and
      increased neuroinflammation. This is the first evidence demonstrating that ULK4
      is a crucial regulator of myelination, and ULK4 may therefore become a novel
      therapeutic target for hypomyelination diseases.

PMID- 29034509
TI  - 3D diffusion-weighted 129 Xe MRI for whole lung morphometry.
AB  - PURPOSE: To obtain whole lung morphometry measurements from 129 Xe in a single
      breath-hold with 3D multiple b-value 129 Xe diffusion-weighted MRI (DW-MRI) with
      an empirically optimized diffusion time and compressed sensing for scan
      acceleration. METHODS: Prospective three-fold undersampled 3D multiple b-value
      hyperpolarized 129 Xe DW-MRI datasets were acquired, and the diffusion time
      (Delta) was iterated so as to provide diffusive length scale (LmD ) estimates
      from the stretched exponential model (SEM) that are comparable to those from 3
      He. The empirically optimized 129 Xe diffusion time was then implemented with a
      four-fold undersampling scheme and was prospectively benchmarked against 3 He
      measurements in a cohort of five healthy volunteers, six ex-smokers, and two
      chronic obstructive pulmonary disease patients using both SEM-derived LmD and
      cylinder model (CM)-derived mean chord length (Lm). RESULTS: Good agreement
      between the mean 129 Xe and 3 He LmD (mean difference, 2.2%) and Lm (mean
      difference, 1.1%) values was obtained in all subjects at an empirically optimized
      129 Xe Delta = 8.5 ms. CONCLUSION: Compressed sensing has facilitated single
      breath 3D multiple b-value 129 Xe DW-MRI acquisitions, and results at 129 Xe
      Delta = 8.5 ms indicate that 129 Xe provides a viable alternative to 3 He for
      whole lung morphometry mapping with either the SEM or CM. Magn Reson Med 79:2986
      2995, 2018. (c) 2017 The Authors Magnetic Resonance in Medicine published by
      Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance
      in Medicine. This is an open access article under the terms of the Creative
      Commons Attribution License, which permits use, distribution and reproduction in
      any medium, provided the original work is properly cited.

PMID- 29034511
TI  - Computationally Efficient Combination of Multi-channel Phase Data From Multi-echo
      Acquisitions (ASPIRE).
AB  - PURPOSE: To develop a simple method for combining multi-echo phase information
      from a number of coils in an array that requires no volume coil or additional
      scans and yields signal-to-noise ratio-optimal images that reflect only DeltaB0
      related phase. THEORY AND METHODS: Two SNR optimal coil combination methods were
      developed which retrieve the DeltaB0-related phase by determining the coil
      dependent phase offsets. The first variant, MCPC-3D-S, requires the unwrapping of
      one phase image; the second variant, ASPIRE, allows unwrapping to be avoided if
      two echoes j and k satisfy the echo time relation m?TEk=(m+1)?TEj, where m is an
      integer, making this a particularly fast and robust approach. Both developed
      methods constitute improvements over a prior method, MCPC-3D, in terms of
      robustness and computational expense. RESULTS: In the brain at 7 T, phase
      matching and contrast-to-noise ratio were higher with MCPC-3D-S and ASPIRE than
      with phase difference reconstruction, and similar to the reference coil-dependent
      Roemer combination. Unlike the Roemer and virtual reference coil methods, the
      proposed approaches also eliminated all non- DeltaB0-related phase. CONCLUSION:
      MCPC-3D-S is an improvement over prior multi-echo methods, which is useful if the
      ASPIRE echo time condition cannot be fulfilled. ASPIRE is a particularly fast and
      robust approach that runs on the scanner's reconstructor in a small fraction of
      the acquisition time. Magn Reson Med 79:2996-3006, 2018. (c) 2017 International
      Society for Magnetic Resonance in Medicine.

PMID- 29034512
TI  - Superficial temporal artery perforator flap: Anatomic study of number and
      reliability of distal branches of the superficial temporal artery and clinical
      applications in three cases.
AB  - BACKGROUND: Limited information is available about the anatomical feasibility and
      clinical applications of flaps based on distal divisions of the superficial
      temporal artery (STA). The aim of this study was to investigate the anatomy of
      the STA, focusing on the number and reliability of distal branches and to show
      representative cases for the use of such flaps for zygomatic, parieto-frontal and
      occipital reconstructions. METHODS: Fifty volunteers were examined bilaterally by
      Doppler to investigate the presence and variability of the distal divisions of
      STA branches. Dissection was performed on 14 temporal regions of 7 fresh
      cadavers. Three cases of reconstruction following skin cancer in the zygomatic (7
      * 5 cm defect), parieto-frontal (4 * 4 cm defect) and occipital areas (4 * 2 cm
      defect) are presented. All the flaps were pedicled and based on a single vessel.
      RESULTS: In all the 50 volunteers, the parietal branch split into 2 +/- 0
      branches (anterior and posterior), bilaterally, while an average of 2.84 +/- 0.46
      and 2.82 +/- 0.48 branches originated from the frontal vessel on the right and
      left side, respectively. 2 +/- 0 parietal and 3 +/- 0 frontal (superior, central,
      and inferior) cutaneous perforator branches were identified in all cadaveric
      specimens. Flaps (4 * 10 cm, 5 * 7 cm, and 2 * 5 cm, respectively, width *
      length) healed uneventfully providing stable coverage. CONCLUSIONS: STA distal
      perforator branches proved to be anatomically constant in both the cadaveric and
      clinical settings. Although a larger series of cases is needed, island flaps
      based on such vessels may represent a versatile surgical option, allowing a wide
      range of reconstructions in the different facial subunits.

PMID- 29034515
TI  - Reversible Oxidative Se-Se Coupling of Phosphine Selenides by Ph3 Sb(OTf)2.
AB  - Salts of diphosphoniumdiselenide dications ([R3 PSeSePR3 ][OTf]2 ) have been
      isolated from reactions of trialkylphosphine selenides with triphenylantimony
      bistriflate. The redox process is speculated to proceed via a cationic
      coordination complex [Ph3 SbL2 ][OTf]2 (L=Me3 PSe, iPr3 PSe), which is also
      formed in the reaction of [R3 PSeSePR3 ][OTf]2 with Ph3 Sb. The observations
      indicate that the reductive elimination of [R3 PSeSePR3 ]2+ from [Ph3 Sb(SePR3 )2
      ]2+ is reversible through the oxidative addition of [R3 PSeSePR3 ]2+ to Ph3 Sb.

PMID- 29034514
TI  - Measurement of Murine Single-Kidney Glomerular Filtration Rate Using Dynamic
      Contrast-Enhanced MRI.
AB  - PURPOSE: To develop and validate a method for measuring murine single-kidney
      glomerular filtration rate (GFR) using dynamic contrast-enhanced MRI (DCE-MRI).
      METHODS: This prospective study was approved by the Institutional Animal Care and
      Use Committee. A fast longitudinal relaxation time (T1 ) measurement method was
      implemented to capture gadolinium dynamics (1 s/scan), and a modified two
      compartment model was developed to quantify GFR as well as renal perfusion using
      16.4T MRI in mice 2 weeks after unilateral renal artery stenosis (RAS, n = 6) or
      sham (n = 8) surgeries. This approach was validated by comparing model-derived
      GFR and perfusion to those obtained by fluorescein isothiocyanante (FITC)-inulin
      clearance and arterial spin labeling (ASL), respectively, using the Pearson's and
      Spearman's rank correlations and Bland-Altman analysis. RESULTS: The
      compartmental model provided a good fitting to measured gadolinium dynamics in
      both normal and RAS kidneys. The proposed DCE-MRI method offered assessment of
      single-kidney GFR and perfusion, comparable to the FITC-inulin clearance
      (Pearson's correlation coefficient r = 0.95 and Spearman's correlation
      coefficient rho = 0.94, P < 0.0001, and mean difference -7.0 +/- 11.0 MUL/min)
      and ASL (r = 0.92 and rho = 0.84, P < 0.0001, and mean difference 4.4 +/- 66.1
      mL/100 g/min) methods. CONCLUSION: The proposed DCE-MRI method may be useful for
      reliable noninvasive measurements of single-kidney GFR and perfusion in mice.
      Magn Reson Med 79:2935-2943, 2018. (c) 2017 International Society for Magnetic
      Resonance in Medicine.

PMID- 29034516
TI  - Identifying gene-gene interactions using penalized tensor regression.
AB  - Gene-gene (G*G) interactions have been shown to be critical for the fundamental
      mechanisms and development of complex diseases beyond main genetic effects. The
      commonly adopted marginal analysis is limited by considering only a small number
      of G factors at a time. With the "main effects, interactions" hierarchical
      constraint, many of the existing joint analysis methods suffer from prohibitively
      high computational cost. In this study, we propose a new method for identifying
      important G*G interactions under joint modeling. The proposed method adopts
      tensor regression to accommodate high data dimensionality and the penalization
      technique for selection. It naturally accommodates the strong hierarchical
      structure without imposing additional constraints, making optimization much
      simpler and faster than in the existing studies. It outperforms multiple
      alternatives in simulation. The analysis of The Cancer Genome Atlas (TCGA) data
      on lung cancer and melanoma demonstrates that it can identify markers with
      important implications and better prediction performance.

PMID- 29034517
TI  - Medication use by adolescents and adults with fragile X syndrome.
AB  - BACKGROUND: The behavioural challenges and medical conditions associated with
      fragile X syndrome (FXS) can lead to increased need for medications. METHOD: This
      longitudinal study examined the use of prescription medications for psychotropic
      and non-psychotropic purposes by adolescents and adults with FXS drawn from a
      North American community sample (N = 105). Odds and probabilities of continuing
      or discontinuing medication were calculated. Predictors of medication use were
      calculated. RESULTS: More than two-thirds took psychotropic medication, and about
      one-quarter took non-psychotropic medication. Over a 3-year period, those who
      initially took prescription medications were considerably more likely to remain
      on medications than to stop. Individuals with more autism symptoms, more
      behavioural problems, a mental health diagnosis, and greater family income were
      significantly more likely to use psychotropic medication 3 years later.
      Individuals who had more health problems, a mental health diagnosis, and were
      female were more likely to use non-psychotropic medication over this time period.
      CONCLUSIONS: Findings highlight the elevated and ongoing use of medication by
      individuals with FXS. Implications for social and behavioural research on FXS are
      discussed.

PMID- 29034518
TI  - Analysis of treatment goal alignment between Japanese psoriasis patients and
      their paired treating physicians.
AB  - BACKGROUND: Appropriate goal-oriented treatment strategies are important for
      optimal treatment outcomes and may prevent under-treatment. As treatment goals
      vary by patient, a study to examine treatment goals is more meaningful when
      patients and their physicians are paired. There has not been any study that
      examines alignment between paired psoriasis patients and physicians in real-world
      clinical practice using skin clearance as a treatment goal indicator. OBJECTIVES:
      To evaluate treatment goal alignment between psoriasis patients and their paired
      physicians, and to quantitatively identify factors associated with goal
      misalignment. METHODS: The study was a nationwide multicenter cross-sectional
      observational study. Subjects were physician-reported moderate-to-severe
      psoriasis patients with a history of systemic treatments, directly paired with
      their treating physicians. Subjects completed surveys independently. Treatment
      goals included seven categories, and patient-physician pairs were grouped as
      'aligned' or 'misaligned' when the answers were the same or different,
      respectively. RESULTS: A total of 425 pairs (mean response rate, 94.7%) of
      responses were collected from 54 sites (64.8% general practitioners or clinics;
      35.2% university or large hospitals). Treatment goal misalignment was found in
      67.9% of the patient-physician pairs. The misalignment was mainly 'patient
      predominant' (60.9%) indicating that patients had higher goals ('complete
      clearance') than physicians. In the multivariate logistic regression analyses,
      patients' treatment expectation for 'complete clearance' [odds ratio (OR): 1.927;
      95% confidential interval (CI): 1.232-3.016] and physician rating of 'level of
      understanding on treatment options' being low (OR: 1.552, 95% CI; 1.082-2.227)
      were significant factors for treatment goal misalignment. CONCLUSIONS: The
      majority of treatment goal misalignment was found between paired psoriasis
      patients and their treating physicians in Japan. The most important contributing
      factors to misalignment were patients' treatment expectation for 'complete
      clearance' and physicians' rating of their patients' 'level of understanding on
      treatment options' being low.

PMID- 29034519
TI  - Flexible Aqueous Li-Ion Battery with High Energy and Power Densities.
AB  - A flexible and wearable aqueous symmetrical lithium-ion battery is developed
      using a single LiVPO4 F material as both cathode and anode in a "water-in-salt"
      gel polymer electrolyte. The symmetric lithium-ion chemistry exhibits high energy
      and power density and long cycle life, due to the formation of a robust solid
      electrolyte interphase consisting of Li2 CO3 -LiF, which enables fast Li-ion
      transport. Energy densities of 141 Wh kg-1 , power densities of 20 600 W kg-1 ,
      and output voltage of 2.4 V can be delivered during >4000 cycles, which is far
      superior to reported aqueous energy storage devices at the same power level.
      Moreover, the full cell shows unprecedented tolerance to mechanical stress such
      as bending and cutting, where it not only does not catastrophically fail, as most
      nonaqueous cells would, but also maintains cell performance and continues to
      operate in ambient environment, a unique feature apparently derived from the high
      stability of the "water-in-salt" gel polymer electrolyte.

PMID- 29034520
TI  - Substitution Reactions at Dipp BIAN Supported Fluoroantimony Cations Yielding
      Cyanoantimony and Azidoantimony Cations.
AB  - This work presents new cationic coordination complexes of antimony with the 1,2
      bis[(2,6-diisopropylphenyl)imino]acenaphthene (Dipp BIAN) ligand system. The
      fluoroantimony complexes [SbF(Dipp BIAN)][OTf]2 and [SbF2 (Dipp BIAN)][OTf] have
      been successfully isolated and characterized. The fluorine substituent in the
      Lewis acidic complex [SbF(Dipp BIAN)][OTf]2 can be selectively replaced without
      degradation of the Sb-Dipp BIAN interaction to give the first dicationic azido
      and cyano derivatives, [Sb(CN)(Dipp BIAN)][OTf]2 and [Sb(N3 )(Dipp BIAN)][OTf]2 ,
      which have been isolated and structurally characterized.

PMID- 29034521
TI  - Sleep spindle detection using multivariate Gaussian mixture models.
AB  - In this research study we have developed a clustering-based automatic sleep
      spindle detection method that was evaluated on two different databases. The
      databases consisted of 20 all-night polysomnograph recordings. Past detection
      methods have been based on subject-independent and some subject-dependent
      parameters, such as fixed or variable thresholds to identify spindles. Using a
      multivariate Gaussian mixture model clustering technique, our algorithm was
      developed to use only subject-specific parameters to detect spindles. We have
      obtained an overall sensitivity range (65.1-74.1%) at a (59.55-119.7%) false
      positive proportion.

PMID- 29034522
TI  - Parent-Adolescent Discrepancies in Perceived Parental Sacrifice and Adolescent
      Developmental Outcomes in Poor Chinese Families.
AB  - Parents and adolescents perceive family processes differently. This study
      examined how convergence and divergence of parent-perceived and adolescent
      perceived parental sacrifice influenced adolescent developmental outcomes in a
      sample of 275 poor intact Chinese families in Hong Kong. The results of
      polynomial regression analyses indicated that the interaction of fathers' and
      adolescents' perceptions of paternal sacrifice negatively predicted adolescent
      resilience and cognitive competence. Similar findings were identified in maternal
      sacrifice. Cluster analysis further showed that adolescents exhibited greater
      resilience and cognitive competence in families with parent-adolescent convergent
      perceptions of high levels of parental sacrifice than did those in families with
      parent-adolescent divergent views. Theoretical, methodological, and practical
      implications of the results are discussed.

PMID- 29034523
TI  - Immobilised Electrocatalysts: Nafion Particles Doped with Ruthenium(II) Tris(2,2'
      bipyridyl).
AB  - Nafion particles doped with ruthenium(II) tris(2,2'-bipyridyl) are synthesized by
      using a re-precipitation method. Characterization including SEM sizing and
      quantification of Ru(bpy)32+ in the Nafion particles using UV/Vis spectroscopy
      was conducted. The synthesized Ru-Nafion particles were investigated
      electrochemically at both ensemble and single particle levels. Voltammetry of the
      drop-cast Ru-Nafion particles evidences the successful incorporation of
      Ru(bpy)32+ into the Nafion particle but only a small fraction of the incorporated
      Ru(bpy)32+ was detected due at least in part to the formation of the likely
      agglomerated and irregular "mat" associated with the dropcast technique. In
      contrast, nano-impact experiments provided a quantitative determination of the
      amount of Ru(bpy)32+ in single Ru-Nafion particles. Finally, oxidation of
      solution-phase oxalate mediated by Ru(bpy)32+ within individual Nafion particles
      was observed, showing the electrocatalytic properties of the Ru-Nafion particles.

PMID- 29034524
TI  - Carotid chemoreceptor control of muscle sympathetic nerve activity in hypobaric
      hypoxia.
AB  - NEW FINDINGS: What is the central question of this study? High-altitude hypoxia
      increases muscle sympathetic nerve activity (MSNA), but whether intravenous
      infusion of dopamine, to blunt the responsiveness of the carotid chemoreceptors,
      reduces MSNA at high altitude is not known. What is the main finding and its
      importance? Muscle sympathetic nerve activity was elevated after 15-17 days of
      high-altitude hypoxia (3454 m) compared with values at 'sea level' (432 m).
      However, intravenous dopamine infusion to blunt the responsiveness of the carotid
      chemoreceptors did not significantly decrease MSNA either at sea level or at high
      altitude, suggesting that high-altitude sympathoexcitation arises via a different
      mechanism. High-altitude hypoxia causes pronounced sympathoexcitation, but the
      underlying mechanisms remain unclear. We tested the hypothesis that i.v. infusion
      of dopamine to attenuate carotid chemoreceptor responsiveness would reduce muscle
      sympathetic nerve activity (MSNA) at high altitude. Nine healthy individuals
      [mean (SD); 26 (4) years of age] were studied at 'sea level' (SL; Zurich) and at
      high altitude (ALT; 3454 m; 15-17 days after arrival), both while breathing the
      ambient air and during an acute incremental hypoxia test (eight 3 min stages;
      partial pressure of end-tidal O2 90-45 mmHg). Intravenous infusions of dopamine
      (3 MUg kg-1  min-1 ) and placebo (saline) were administered on both study days,
      according to a single-blind randomized cross-over design. Sojourn to high
      altitude decreased the partial pressure of end-tidal O2 (to ~60 mmHg) and
      increased minute ventilation [VE; mean +/- SEM, SL versus ALT: saline, 8.6 +/-
      0.5 versus 11.3 +/- 0.6 l min-1 ; dopamine, 8.2 +/- 0.5 versus 10.6 +/- 0.8 l min
      1 ; P < 0.05] and MSNA burst frequency by ~80% [SL versus ALT: saline, 16 +/- 3
      versus 28 +/- 4 bursts min-1 ; dopamine, 16 +/- 4 versus 31 +/- 4 bursts min-1 ;
      P < 0.05) when breathing the ambient air, but were not different with dopamine.
      Increases in MSNA burst frequency and VE during the acute incremental hypoxia
      test were greater at ALT than SL (P < 0.05). Dopamine did not affect the
      magnitude of the MSNA burst frequency response to acute incremental hypoxia at
      either SL or ALT. However, VE was lower with dopamine than saline administration
      throughout the acute incremental hypoxia test at ALT. These data indicate that
      i.v. infusion of low-dose dopamine to blunt the responsiveness of the carotid
      chemoreceptors does not significantly decrease MSNA at high altitude.

PMID- 29034526
TI  - Brugada phenocopy caused by a compressive mediastinal tumor.
AB  - Recently, it has been shown that even experts in electrocardiography cannot
      differentiate the electrocardiographic pattern of genuine Brugada syndrome (BrS)
      from Brugada phenocopy (BrP). For this reason, this differentiation depends on
      the presence of established criteria both for BrS and BrP. In this manuscript, we
      present a patient with type 1 Brugada electrocardiographic pattern caused by
      expansive anterior mediastinal non-Hodgkin's lymphoma (NHL) with mechanical
      compression on the right ventricular outflow tract. The electrocardiographic
      pattern disappeared rapidly after antineoplastic measures.

PMID- 29034525
TI  - Reliability and validity of severity dimensions of psychopathology assessed using
      the Structured Clinical Interview for DSM-5 (SCID).
AB  - This study examined whether the Structured Clinical Interview for DSM (SCID), a
      widely used semistructured interview designed to assess psychopathology
      categorically, can be adapted to identify reliable and valid severity dimensions
      of psychopathology. The present study also examined whether these severity
      dimensions have better psychometric properties (internal consistency, test-retest
      reliability, and concurrent and predictive validity) than categorical diagnoses.
      Participants (N = 234) were recruited from the community and clinics. Retest
      reliability and prospective predictive validity (symptoms and functioning 1 year
      later) were examined in subsamples of participants. Dimensional severity scales
      were created from an adapted version of the SCID for both current and lifetime
      major depression, alcohol, substance, post-traumatic stress disorder, panic,
      agoraphobia, social anxiety, specific phobia, obsessive-compulsive disorder, and
      generalized anxiety disorder. The SCID's severity scales demonstrated substantial
      internal consistency (all Cronbach's alphas >.80), test-retest reliability, and
      concurrent and predictive validity. Symptom severity scales demonstrated
      significant incremental validity over and above categorical diagnoses for both
      current and prospective outcomes. The psychometric properties of SCID-identified
      symptom scales were far superior to the psychometrics of categorical diagnoses
      for both current and lifetime psychopathology. These results highlight the
      feasibility and utility of the SCID to assess reliable and valid symptom severity
      dimensions of both current and lifetime psychopathology.

PMID- 29034528
TI  - Patients with a new variant of endemic pemphigus foliaceus have autoantibodies
      against arrector pili muscle, colocalizing with MYZAP, p0071, desmoplakins 1 and
      2 and ARVCF.
AB  - BACKGROUND: We identified a new variant of endemic pemphigus foliaceus in El
      Bagre, Colombia, South America, which we term El Bagre-EPF, and observed
      reactivity to arrector pili muscle (APM), thus we tested for autoimmunity to APM.
      METHODS: We took skin biopsies from 30 patients with El Bagre-EPF and 30 healthy
      controls (HCs) matched by age, sex and occupation, who were all from the endemic
      area, and tested these using direct immunofluorescence (DIF), confocal
      microscopy, immunohistochemistry and immunoblotting (IB). RESULTS: Of the 30
      patients with El Bagre-EPF, 27 had autoantibodies to APM that colocalized with
      commercial antibodies to myocardium-enriched zonula occludens-1-associated
      protein (MYZAP), desmoplakin (DP)1 and DP2, plakophilin 4, and Armadillo repeat
      gene deleted in velo-cardio-facial syndrome (ARVCF) (P < 0.001, Fisher exact
      test). The positive staining also colocalized with Junctional Adhesion Molecule 1
      (JAM-A), a control antibody for gap cell junctions. No HC samples were positive.
      In 27 of the 30 patients, serum that was APM-positive also displayed IB
      colocalization of their autoantibody molecular weights with the Progen antibodies
      (P < 0.001, Fisher exact test). CONCLUSIONS: Patients affected by El Bagre-EPF
      have autoantibodies to APM, colocalizing with the antibodies MYZAP, ARVCF, p0071,
      DP1 and DP2, suggesting that these molecules are El Bagre-EPF antigens. Further,
      all of these antigens represent components of cell junctions, indicating that the
      immune response is directed, at least partially, against cell junctions. The
      immune response in patients affected by El Bagre-EPF is polyclonal, and it
      includes B and T lymphocytes, mast cells, IgG, IgA, IgM, IgD, IgE, fibrinogen,
      albumin, complement/C1q, C3c and C4.

PMID- 29034527
TI  - Age of onset or age at assessment-that is the question: Estimating newly incident
      alcohol drinking and rapid transition to heavy drinking in the United States,
      2002-2014.
AB  - Age-specific incidence estimates are important and useful facts in psychiatric
      epidemiology, but incidence estimation can be challenging. Methods artifacts are
      possible. In the United States, where the minimum legal drinking age is 21 years,
      recent cross-sectional field research on 12- to 25-year-olds applied conventional
      "age-at-assessment" approaches (AAA) for incidence estimation based on 12-month
      recall. Estimates disclosed unexpected nonlinear patterns in age-specific
      incidence estimates for both drinking onset and for transitioning from first
      drink to heavy drinking. Here, our aim is to draw attention to an "age of onset"
      (AOO) alternative to AAA approaches and to verify whether the AOO approach also
      discloses nonlinearity. Yearly data are from U.S. nationally representative
      samples drawn and assessed for National Surveys on Drug Use and Health, 2002
      2014, with standardized audio computer-assisted self-interview assessments for
      drinking outcomes. Both AAA and AOO approaches show nonlinearities, with an
      unexpected dip in drinking incidence rates after age 18 and before the age 21
      minimum legal drinking age. The AOO and the AAA approaches disclosed similar age
      specific patterns. We discuss advantages of the AOO approach when nonlinear
      incidence patterns can be anticipated, but we conclude that the AAA approach has
      not created an artifactual nonlinear pattern.

PMID- 29034529
TI  - Reliability of muscle blood flow and oxygen consumption response from exercise
      using near-infrared spectroscopy.
AB  - NEW FINDINGS: What is the central question of this study? Continuous-wave near
      infrared spectroscopy, coupled with venous and arterial occlusions, offers an
      economical, non-invasive alternative to measuring skeletal muscle blood flow and
      oxygen consumption, but its reliability during exercise has not been established.
      What is the main finding and its importance? Continuous-wave near-infrared
      spectroscopy devices can reliably assess local skeletal muscle blood flow and
      oxygen consumption from the vastus lateralis in healthy, physically active
      adults. The patterns of response exhibited during exercise of varying intensity
      agree with other published results using similar methodologies, meriting
      potential applications in clinical diagnosis and therapeutic assessment. Near
      infrared spectroscopy (NIRS), coupled with rapid venous and arterial occlusions,
      can be used for the non-invasive estimation of resting local skeletal muscle
      blood flow (mBF) and oxygen consumption (mVO2), respectively. However, the day-to
      day reliability of mBF and mVO2 responses to stressors such as incremental
      dynamic exercise has not been established. The aim of this study was to determine
      the reliability of NIRS-derived mBF and mVO2 responses from incremental dynamic
      exercise. Measurements of mBF and mVO2 were collected in the vastus lateralis of
      12 healthy, physically active adults [seven men and five women; 25 (SD 6) years
      old] during three non-consecutive visits within 10 days. After 10 min rest,
      participants performed 3 min of rhythmic isotonic knee extension (one extension
      every 4 s) at 5, 10, 15, 20, 25 and 30% of maximal voluntary contraction (MVC),
      before four venous occlusions and then two arterial occlusions. The mBF and mVO2
      increased proportionally with intensity [from 0.55 to 7.68 ml min-1  (100 ml)-1
      and from 0.05 to 1.86 ml O2  min-1  (100 g)-1 , respectively] up to 25% MVC,
      where they began to plateau at 30% MVC. Moreover, an mBF/mVO2 muscle oxygen
      consumption ratio of ~5 was consistent for all exercise stages. The intraclass
      correlation coefficient for mBF indicated high to very high reliability for 10
      30% MVC (0.82-0.9). There was very high reliability for mVO2 across all exercise
      stages (intraclass correlation coefficient 0.91-0.96). In conclusion, NIRS can
      reliably assess muscle blood flow and oxygen consumption responses to low- to
      moderate-intensity exercise, meriting potential applications in clinical
      diagnosis and therapeutic assessment.

PMID- 29034530
TI  - Gene expression and morphological changes in the intestinal mucosa associated
      with increased permeability induced by short-term fasting in chickens.
AB  - Short-term fasting for 4.5 and 9 hr has been demonstrated to increase intestinal
      permeability (IP) in chickens. This study aimed to investigate the effects of 0,
      4.5, 9 and 19.5 hr fasting on intestinal gene expression and villus-crypt
      architecture of enterocytes in jejunal and ileal samples. On day 38, Ross-308
      male birds were fasted according to their group and then euthanised. Two separate
      intestinal sections (each 2 cm long, jejunum and ileum) were collected. One
      section was utilised for villus height and crypt depth measurements. The second
      section was snap-frozen in liquid nitrogen for quantitative polymerase chain
      reaction (qPCR) analysis of tight junction proteins (TJP) including claudin-1,
      claudin-3, occludin, zonula occludens (ZO-1, ZO-2), junctional adhesion molecules
      (JAM) and E-cadherin. Additionally genes involved in enterocyte protection
      including glucagon-like peptide (GLP-2), heat-shock protein (HSP-70), intestinal
      alkaline phosphatase (IAP), mammalian target of rapamycin (mTOR), toll-like
      receptors (TLR-4), mucin (MUC-2), cluster differentiation (CD-36) and fatty acid
      binding protein (FABP-6) were also analysed. Normally distributed data were
      analysed using one-way analysis of variance ANOVA. Other data were analysed by
      non-parametric one-way ANOVA. Villus height and crypt depth were increased (p <
      .05) only in the ileum after fasting for 4.5 and 9 hr compared with non-fasting
      group. mRNA expression of claudin-3 was significantly reduced in the ileum of
      birds fasted for 9 and 19.5 hr, suggesting a role in IP modulation. However, all
      other TJP genes examined were not statistically different from control.
      Nevertheless, ileal FABP-6 of all fasted groups was significantly reduced, which
      could possibly be due to reduced bile acid production during fasting.

PMID- 29034531
TI  - Sealer penetration and adaptation in root canals with the butterfly effect.
AB  - The butterfly effect is a phenomenon seen in some roots and is related to density
      of dentinal tubules. The aim was to investigate penetration depth and adaptation
      quality of root canal sealers and ProRoot MTA into bucco-lingual and mesio-distal
      aspects of roots with and without the effect. One hundred and twenty teeth were
      decoronated at the cemento-enamel junction. Canals were prepared and assigned to
      obturation groups: gutta-percha with a sealer (AH Plus, EndoREZ, Kerr Pulp Canal
      Sealer, MTA Fillapex) or ProRoot MTA alone (each containing 10 butterfly and 10
      non-butterfly roots). Root sectioning yielded coronal and middle samples.
      Confocal laser scanning and scanning electron microscopy were used to assess
      penetration and adaptation. Teeth with the effect had greater mean penetration
      bucco-lingually (766 MUm) than mesio-distally (184 MUm, P = 0.003). Coronal
      sections had greater penetration (430 MUm) compared with middle (247 MUm, P =
      0.006). In conclusion, greater penetration in roots with the effect may improve
      treatment outcomes.

PMID- 29034532
TI  - Feces nitrogen release induced by different large herbivores in a dry grassland.
AB  - Large herbivores have pronounced effects on nutrient cycling in grasslands. These
      organisms are known to alter the quality and quantity of plant production as well
      as the amounts and quality of plant litter and animal wastes. The generalization
      that the relative quality of detritus inputs is enhanced by herbivores is well
      known, but how this process is affected by diet selection processing and feces
      production of different large herbivores remains largely unstudied. Here, we
      measured how these differences for cattle and sheep on a dry grassland might
      influence nitrogen (N) mineralization from feces. We found that cattle of larger
      body size tended to select the low quality grass Stipa grandis as their major
      food source. In contrast, the subdominant grass Leymus chinensis, with relatively
      high N content, was a majority in the diet of smaller sheep, when palatable forbs
      were insufficient in the field. This diverse diet quality resulted in a C:N ratio
      of cattle feces that was higher than that of sheep feces. Relatively higher
      labile C availability in the cattle feces, namely relatively higher
      cellulose/hemicellulose contents, promoted microbial growth and in turn
      accelerated cattle feces decomposition. A surprise finding was that the feces
      from cattle mineralized about twice as much N as feces from sheep, despite the
      latter having slightly higher N content. From a grassland productivity
      perspective, increasing the proportion of large body-sized species in grazing
      herbivore assemblages perhaps is beneficial to forage productivity and nutrient
      recycling by the rapid degradation of feces.

PMID- 29034533
TI  - Efficacy, tolerability and safety of cannabis-based medicines for chronic pain
      management - An overview of systematic reviews.
AB  - : Medicinal cannabis has already entered mainstream medicine in some countries.
      This systematic review (SR) aimed at evaluating the efficacy, acceptability and
      safety of cannabis-based medicines for chronic pain management. Qualitative
      systematic review of SRs of randomized controlled trials with cannabis-based
      medicines for chronic pain management. The Cochrane databases of SRs, Database of
      Abstracts of Reviews of Effects and PubMed were searched for SR published in the
      period January 2009 to January 2017. Assessment of the methodological quality of
      SR was performed by the AMSTAR checklist. Out of 748 papers identified, 10 SRs
      met the inclusion criteria. The methodological quality was high in four and
      moderate in six SRs. There were inconsistent findings of four SRs on the efficacy
      of cannabis-based medicines in neuropathic pain and of one SR for painful spasms
      in multiple sclerosis. There were consistent results that there was insufficient
      evidence of any cannabis-based medicine for pain management in patients with
      rheumatic diseases (three SRs) and in cancer pain (two SRs). Cannabis-based
      medicines undoubtedly enrich the possibilities of drug treatment of chronic pain
      conditions. It remains the responsibility of the health care community to
      continue to pursue rigorous study of cannabis-based medicines to provide evidence
      that meets the standard of 21st century clinical care. SIGNIFICANCE: We provide
      an overview of systematic reviews on the efficacy, tolerability and safety of
      cannabis-based medicines for chronic pain management. There are inconsistent
      findings of the efficacy of cannabinoids in neuropathic pain and painful spasms
      in multiple sclerosis. There are inconsistent results on tolerability and safety
      of cannabis-based medicines for any chronic pain.

PMID- 29034534
TI  - Corrective emotional experience in an integrative affect-focused therapy:
      Building a preliminary model using task analysis.
AB  - OBJECTIVE: The present study constructed a preliminary process model of
      corrective emotional experience (CEE) in an integrative affect-focused therapy.
      METHOD: Task analysis was used to analyse 6 in-session events taken from 6
      Japanese clients who worked with an integrative affect-focused therapist. The 6
      events included 3 successful CEEs and 3 partially successful CEEs for comparison.
      RESULTS: A rational-empirical model of CEE was generated, which consisted of two
      parallel client change processes, intrapersonal change and interpersonal change,
      and the therapist interventions corresponding to each process. Therapist
      experiential interventions and therapist affirmation facilitated both
      intrapersonal and interpersonal change processes, whereas his relational
      interventions were associated with the interpersonal change process. The
      partially successful CEEs were differentiated by the absence of the component of
      core painful emotions or negative beliefs in intrapersonal change process, which
      seemed crucial for the interpersonal change process to develop. CONCLUSIONS: CEE
      is best represented by a preliminary model that depicts two parallel yet
      interacting change processes. Intrapersonal change process is similar to the
      sequence of change described by the emotional processing model (Pascual-Leone &
      Greenberg, ), whereas interpersonal change process is a unique contribution of
      this study. Interpersonal change process was facilitated when the therapist's
      active stance and use of immediacy responses to make their relational process
      explicit allowed a shared exploration. Therapist affirmation bridged
      intrapersonal change to interpersonal change by promoting an adaptive sense of
      self in clients and forging a deeper emotional connection between the two.

PMID- 29034535
TI  - Psychological effects of Helicobacter pylori-associated atrophic gastritis in
      patients under 50 years: A cross-sectional study.
AB  - BACKGROUND: While gastrointestinal function is known to be closely related to
      psychological status, the influence of Helicobacter pylori-associated atrophic
      gastritis is currently unknown. We aimed to determine whether atrophic gastritis
      status or H. pylori infection is associated with psychological distress or
      depressed mood. MATERIALS AND METHODS: We performed a cross-sectional,
      observational study involving 975 Japanese individuals (503 females; mean age, 44
      +/- 8 years) who underwent a health checkup. Psychological distress was defined
      as a Kessler-6 Scale score >=13 and depressive mood as a Center for
      Epidemiological Studies Depression Scale score >= 16. The odds ratios with 95%
      confidence intervals assessing the risk of psychological distress or depressive
      mood associated with H. pylori infection (H. pylori-specific immunoglobulin G
      levels >10 U/mL) and atrophic gastritis status (pepsinogen I levels < 70 MUg/L
      and pepsinogen I/II ratio < 3) were calculated using multiple logistic analysis
      adjusting for several covariates. RESULTS: Individuals with atrophic gastritis
      had a significantly higher risk of experiencing psychological distress, with
      younger females (<50 years) displaying the highest risk for psychological
      distress and depressive mood regardless of H. pylori infection status. Among
      females aged <50 years, H. pylori-seropositive participants with atrophic
      gastritis (HP+AG+) showed the highest risk of psychological distress (OR, 16.4;
      95% CI, 3.45-94.9) and depression (OR, 2.86; 95% CI, 1.31-6.05), using HP-AG-
      status as the reference. CONCLUSIONS: Our findings support the results of
      previous animal studies regarding the psychological response to gastritis in
      humans. Further studies are needed to elucidate whether H. pylori eradication
      provides psychological benefits.

PMID- 29034536
TI  - Family Functioning and Relationship Quality for Adolescents in Family-based
      Treatment with Severe Anorexia Nervosa Compared with Non-clinical Adolescents.
AB  - This longitudinal study explored family functioning and relationship quality for
      adolescents with severe anorexia nervosa (AN). An important outcome given healthy
      family functioning supports effective adolescent development. Fifty-four female
      adolescents and their parents, treated with family-based treatment after
      inpatient admission, and 49 non-clinical age-matched adolescents and their
      parents were compared at assessment and 6 months after session 20. At baseline,
      AN group mothers and fathers reported poorer family function. AN adolescents were
      notably similar to controls, reporting poorer function in only one domain. There
      were no changes for adolescents, an improvement for mothers in the AN group, but
      an increase in perceived impairment for fathers in both groups, with AN fathers
      more affected. The similarity in adolescent reports and the increase for fathers
      over time may indicate that normal adolescent family processes occur even in the
      midst of serious illness. There is a need to provide intervention to ameliorate
      the impact of treatment on parents. Copyright (c) 2017 John Wiley & Sons, Ltd and
      Eating Disorders Association.

PMID- 29034537
TI  - How effective and fair is user fee removal? Evidence from Zambia using a pooled
      synthetic control.
AB  - Despite its high political interest, the impact of removing user charges for
      health care in low-income settings remains a debatable issue. We try to clear up
      this contentious issue by estimating the short-term effects of a policy change
      that occurred in 2006 in Zambia, when 54 of 72 districts removed fees. We use a
      pooled synthetic control method in order to estimate the causal impact of the
      policy on health care use, the provider chosen, and out-of-pocket medical
      expenses. We find no evidence that user fee removal increased health care
      utilisation, even among the poorest group. However, we find that the policy is
      likely to have led to a substitution away from the private sector for those using
      care and that it virtually eliminated medical expenditures, thereby providing
      financial protection to service users. We estimate that the policy was equivalent
      to a transfer of US$3.2 per health visit for the 50% richest but of only US$1.1
      for the 50% poorest.

PMID- 29034538
TI  - Association of insomnia severity with well-being, quality of life and health care
      costs: A cross-sectional study in older adults with chronic pain (PainS65+).
AB  - BACKGROUND: Insomnia is one of the most common complaints in chronic pain. This
      study aimed to evaluate the association of insomnia with well-being, quality of
      life and health care costs. METHODS: The sample included 2790 older individuals
      (median age = 76; interquartile range [IQR] = 70-82) with chronic pain. The
      participants completed a postal survey assessing basic demographic data, pain
      intensity and frequency, height, weight, comorbidities, general well-being,
      quality of life and the insomnia severity index (ISI). Data on health care costs
      were calculated as costs per year (? prices) and measured in terms of outpatient
      and inpatient care, pain drugs, total drugs and total health care costs. RESULTS:
      The overall fraction of clinical insomnia was 24.6% (moderate clinical insomnia:
      21.9% [95% CI: 18.8-23.3]; severe clinical insomnia: 2.7% [95% CI: 1.6-3.2]).
      Persons who reported clinical insomnia were more likely to experience pain more
      frequently with higher pain intensity compared to those reported no clinically
      significant insomnia. Mean total health care costs were ? 8469 (95% CI: ?4029
      ?14,271) for persons with severe insomnia compared with ? 4345 (95% CI: ?4033
      ?4694) for persons with no clinically significant insomnia. An association
      between severe insomnia, well-being, quality of life, outpatient care, total
      drugs costs and total health care costs remained after controlling for age, sex,
      pain intensity, frequency, body mass index and comorbidities using linear
      regression models. CONCLUSIONS: Our results determine an independent association
      of insomnia with low health-related quality of life and increased health care
      costs in older adults with chronic pain. SIGNIFICANCE: The concurrence and the
      severity of insomnia among older adults with chronic pain were associated with
      decreased well-being and quality of life, and increased health care costs to
      society.

PMID- 29034539
TI  - Recurrent extensive anterior myocardial infarction with left and right bundle
      branch block.
AB  - The diagnosis of myocardial infarction with left bundle branch block is
      difficult. We report a case of 56-year-old man with old extensive anterior
      myocardial infarction and left bundle branch block (masked each other). The
      recurrent myocardial infarction indicated right bundle branch block and first
      degree atrioventricular block, making a clear diagnosis of complicated and
      interesting ECG.

PMID- 29034541
TI  - Characteristic component profiling and identification of different Uncaria
      species based on high-performance liquid chromatography-photodiode array
      detection tandem ion trap and time of flight mass spectrometry coupled with rDNA
      ITS sequence.
AB  - Uncaria is a multi-source herb and its species identification has become a
      bottleneck in quality control. To study the identification method of different
      Uncaria species herbs through HPLC-MS coupled with rDNA Internal Transcribed
      Spacer (rDNA ITS) sequence, both plant morphological traits and molecular
      identification were used to determine the species of every collected Uncaria
      herb. The genetic analysis of different Uncaria species was performed using their
      rDNA ITS sequence as a molecular marker. Meanwhile, the phylogenetic
      relationships of 22 samples from six Uncaria species were divided and classified
      clearly. By optimizing the chromatographic conditions, a practical HPLC method to
      differentiate various varieties of Uncaria herbs was set up based on a set of
      characteristic components across each species. A high-performance liquid
      chromatography-photodiode array detector tandem ion trap and time of flight mass
      spectrometry technique combined with reference substances was utilized to derive
      21 characteristic compounds containing six groups of six Uncaria species in
      China. Thus, this study provides a feasible method to solve the current problem
      of confusion in Uncaria species, and makes a significant step forward in the
      appropriate clinical use, in-depth research and further utilization of different
      Uncaria species.

PMID- 29034540
TI  - Ursolic acid enhances the therapeutic effects of oxaliplatin in colorectal cancer
      by inhibition of drug resistance.
AB  - It has been reported that ursolic acid has anti-tumor activity and it enhances
      the therapeutic effect of oxaliplatin in colorectal cancer (CRC). However, the
      underlying mechanisms remain unknown. In the present study, the mechanisms of the
      enhancement of therapeutic effects through use of ursolic acid were investigated.
      We treated CRC cell lines HCT8 and SW480 with ursolic acid and oxaliplatin and
      monitored the effects on cell proliferation, apoptosis, reactive oxygen species
      (ROS) production and drug resistance gene production. We discovered that
      treatment with a combination of ursolic acid and oxaliplatin resulted in
      significant inhibition of cell proliferation, significantly increased apoptosis
      and ROS production, and significant inhibition of drug resistance gene
      expression. Our study provided evidence that ursolic acid enhances the
      therapeutic effects of oxaliplatin in colorectal cancer by ROS-mediated
      inhibition of drug resistance.

PMID- 29034542
TI  - Time-Frequency Analysis of Increases in Vaginal Blood Perfusion Elicited by Long
      Duration Pudendal Neuromodulation in Anesthetized Rats.
AB  - OBJECTIVES: Female sexual dysfunction (FSD) affects a significant portion of the
      population. Although treatment options for FSD are limited, neuromodulation for
      bladder dysfunction has improved sexual function in some women. A few studies
      have investigated peripheral neuromodulation for eliciting changes in vaginal
      blood flow, as a proxy for modulating genital sexual arousal, however results are
      generally transient. Our central hypothesis is that repeated or extended-duration
      pudendal nerve stimulation can elicit maintained vaginal blood flow increases.
      MATERIALS AND METHODS: Under ketamine anesthesia, the pudendal nerve of 14 female
      rats was stimulated at varying frequencies (1-100 Hz) and durations (0.15-60
      min). Vaginal blood perfusion was measured with a laser Doppler flowmetry probe.
      Changes in blood perfusion were determined through raw signal analysis and
      increases in the energy of neurogenic (0.076-0.200 Hz) and myogenic (0.200-0.740
      Hz) frequency bands through wavelet analysis. Additionally, a convolution model
      was developed for a carry-over stimulation effect. RESULTS: Each experiment had
      significant increases in vaginal blood perfusion due to pudendal nerve
      stimulation. In addition, there were large concurrent increases in neurogenic and
      myogenic frequency-band energy in 11/14 experiments, with an average maximal
      response at 31.3 min after stimulation initiation. An effective stimulation model
      with a 30-min carry-over effect had a stronger correlation to blood perfusion
      than the stimulation period itself. CONCLUSIONS: Repeated or extended-duration
      pudendal nerve stimulation can elicit maintained increases in vaginal blood
      perfusion. This work indicates the potential for pudendal neuromodulation as a
      method for increasing genital arousal as a potential treatment for FSD.

PMID- 29034545
TI  - A pilot intervention to reduce postpartum weight retention and central adiposity
      in first-time mothers: results from the mums OnLiNE (Online, Lifestyle, Nutrition
      & Exercise) study.
AB  - BACKGROUND: Postpartum weight retention (PPWR) increases the risk for obesity and
      complications during subsequent pregnancies. Few interventions have been
      successful in limiting PPWR in mothers. The present study assessed the
      effectiveness of the mums OnLiNE (Online, Lifestyle, Nutrition & Exercise)
      intervention with respect to reducing PPWR and improving diet, physical activity
      and sedentary behaviour. METHODS: A subsample of first-time mothers enrolled in
      the Extended Melbourne Infant Feeding Activity and Nutrition Trial (InFANT
      Extend) completed the nonrandomised mums OnLiNE intervention. Women in the
      intervention (I) group (n = 28) received access to an online calorie tracking
      program, smartphone app, three telephone counselling calls with a dietitian and
      written material. Women in two comparison groups (CI and C2) (n = 48; n = 43)
      were from the control (C1) and intervention (C2) arms of InFANT Extend and
      received no additional support. Weight and waist circumference were measured
      objectively. Written surveys assessed diet and physical activity. Sedentary
      behaviour was self-reported. Linear and logistic regression assessed changes in
      outcomes between groups from 9 to 18 months postpartum. RESULTS: Mean PPWR
      decreased in the (I) group (-1.2 kg) and the C2 group (-1.2 kg), although the
      changes were not significant. Mean waist circumference for all groups exceeded
      recommendations at baseline but decreased to below recommendations for women in
      the (I) group (78.3 cm) and significantly for the (I) group (-6.4 cm) compared to
      C1 (-1.1 cm; P = 0.002) and C2 (-3.3 cm; P = 0.001). Changes in diet, physical
      activity or sedentary behaviour were not significant. CONCLUSIONS: The online
      intervention reported in the present study shows promise with respect to reducing
      waist circumference in postpartum women. Further evidence of strategies that may
      improve weight and related behaviours in this target group is needed.

PMID- 29034544
TI  - CYP2U1 activity is altered by missense mutations in hereditary spastic paraplegia
      56.
AB  - Hereditary spastic paraplegia (HSP) is an inherited disorder of the central
      nervous system mainly characterized by gradual spasticity and weakness of the
      lower limbs. SPG56 is a rare autosomal recessive early onset complicated form of
      HSP caused by mutations in CYP2U1. The CYP2U1 enzyme was shown to catalyze the
      hydroxylation of arachidonic acid. Here, we report two further SPG56 families
      carrying three novel CYP2U1 missense variants and the development of an in vitro
      biochemical assay to determine the pathogenicity of missense variants of
      uncertain clinical significance. We compared spectroscopic, enzymatic, and
      structural (from a 3D model) characteristics of the over expressed wild-type or
      mutated CYP2U1 in HEK293T cells. Our findings demonstrated that most of the
      tested missense variants in CYP2U1 were functionally inactive because of a loss
      of proper heme binding or destabilization of the protein structure. We also
      showed that functional data do not necessarily correlate with in silico
      predictions of variants pathogenicity, using different bioinformatic phenotype
      prediction tools. Our results therefore highlight the importance to use
      biological tools, such as the enzymatic test set up in this study, to evaluate
      the effects of newly identified variants in clinical settings.

PMID- 29034543
TI  - PD-L1 expression is mainly regulated by interferon gamma associated with JAK-STAT
      pathway in gastric cancer.
AB  - Despite multidisciplinary treatment for patients with advanced gastric cancer,
      their prognosis remains poor. Therefore, the development of novel therapeutic
      strategies is urgently needed, and immunotherapy utilizing anti-programmed death
      1/-programmed death ligand-1 mAb is an attractive approach. However, as there is
      limited information on how programmed death ligand-1 is upregulated on tumor
      cells within the tumor microenvironment, we examined the mechanism of programmed
      death ligand-1 regulation with a particular focus on interferon gamma in an in
      vitro setting and in clinical samples. Our in vitro findings showed that
      interferon gamma upregulated programmed death ligand-1 expression on solid tumor
      cells through the JAK-signal transducer and activator of transcription pathway,
      and impaired the cytotoxicity of tumor antigen-specific CTL against tumor cells.
      Following treatment of cells with anti-programmed death ligand-1 mAb after
      interferon gamma-pre-treatment, the reduced anti-tumor CTL activity by interferon
      gamma reached a higher level than the non-treatment control targets. In contrast,
      programmed death ligand-1 expression on tumor cells also significantly correlated
      with epithelial-mesenchymal transition phenotype in a panel of solid tumor cells.
      In clinical gastric cancer samples, tumor membrane programmed death ligand-1
      expression significantly positively correlated with the presence of CD8-positive
      T cells in the stroma and interferon gamma expression in the tumor. The results
      suggest that gastric cancer patients with high CD8-positive T-cell infiltration
      may be more responsive to anti-programmed death 1/-programmed death ligand-1 mAb
      therapy.

PMID- 29034546
TI  - Bradykinin system is involved in endometriosis-related pain through endothelin-1
      production.
AB  - BACKGROUND: Endometriosis is a gynaecological disease exhibiting severe pelvic
      pain, but the mechanism of pain production remains unknown. Bradykinin (BK) is
      known as an inflammatory mediator, and shows elevated levels in inflammatory
      diseases such as rheumatoid arthritis. In the present study, we evaluated whether
      BK is involved in endometriosis-related pain. METHODS: Endometriotic lesions were
      used for immunohistochemistry. Primary cultures of endometriotic stromal cells
      (ESC) were stimulated with IL-1beta and/or BK. Quantitative RT-PCR was used to
      evaluate the mRNA expressions of BK receptors (BKR) and endothelin-1 in ESC. The
      concentration of endothelin-1 in cystic fluid of endometrioma or non-endometrioma
      was measured with ELISA. The conditioned medium of ESC stimulated with IL-1beta
      and/or BK was injected intraplantarly in mice, and evaluated whether pain-related
      licking behaviour was elicited. RESULTS: The expressions of BK and BKR in
      endometriotic lesions were observed by immunohistochemistry. In vitro experiments
      showed that IL-1beta induced BKR-B1 and B2 on ESC. Activation of these receptors
      by BK significantly induced endothelin-1 expression in ESC, which was negated
      completely by HOE-140, a BKR-B2 antagonist. The cystic fluid of endometrioma
      contained higher amount of endothelin-1 compared to non-endometrioma.
      Intraplantar injection of the conditioned medium of ESC treated with IL-1beta and
      BK significantly induced licking behaviour, which was suppressed with BQ-123, an
      endothelin type-A receptor antagonist. CONCLUSIONS: The present study
      demonstrated the presence and the function of the BK axis in endometriosis, and
      established a potential new therapy target for endometriosis-related pain.
      SIGNIFICANCE: The present study demonstrated (1) the presence and the function of
      the BK system in endometriosis, (2) activation of BKR induced endothelin-1 in
      endometriotic lesion and (3) blocking endothelin-1 was effective to decrease
      pain.

PMID- 29034547
TI  - Refractory pityriasis rubra pilaris treated with etanercept, adalimumab, or
      ustekinumab: A retrospective investigation.
AB  - Pityriasis rubra pilaris (PRP) is a rare, difficult to treat papulosquamous
      disorder that responds variably to retinoids and immunosuppression. Successful
      use of biologics for treating PRP has been described in the literature by case
      reports and a limited number of case series. To provide additional data, we
      retrospectively analyzed cases of PRP treated with biologics at our institution.
      We identified seven patients with a clear diagnosis of PRP treated with
      adalimumab, etanercept, and/or ustekinumab at our institution from January 1,
      2014 to April 1, 2017. Six of seven patients had type I, adult acquired PRP, and
      one had type V atypical juvenile PRP. In response to tumor necrosis factor (TNF)
      alpha inhibition, two patients had marked responses (>75% improvement in involved
      body surface area), while three patients failed to show any improvement on a TNF
      alpha inhibitor. In two cases of PRP refractory to TNF-alpha inhibition,
      ustekinumab resulted in a partial response (<75% improvement) in one patient and
      no response in the other. Compared to other published data, our cohort was
      substantially more resistant to treatment with biologics, a finding which may
      provide valuable perspective for dermatologists managing refractory PRP in the
      future.

PMID- 29034549
TI  - Effect of Pore Size on the Carbon Dioxide Adsorption Behavior of Porous Liquids
      Based on Hollow Silica.
AB  - Porous liquids are an expanding class of material that has huge potential in gas
      separation and gas adsorption. Pore size has a dramatic influence on the gas
      adsorption of porous liquids. In this article, we chose hollow silica
      nanoparticles as cores, 3-(trihydroxysilyl)-1-propanesulfonic acid (SIT) as
      corona, and inexpensive industrial reagent polyether amine (M2070) as canopy to
      obtain a new type of porous liquids. Hollow silica nanospheres with different
      pore sizes were chosen to investigate the influence of porosity size on CO2
      adsorption capacity of porous liquids. Their chemical structure, morphology,
      thermal behavior and possible adsorption mechanism are discussed in detail. It
      was proved that with similar grafting density, porous liquid that has bigger pore
      size possesses a better CO2 adsorption capacity (2.182 mmol g-1 under 2.5 MPa at
      298 K). More than that, this article demonstrates a more facile and low-cost
      method to obtain porous liquids with good CO2 adsorption capacity, recyclability,
      and huge variability.

PMID- 29034550
TI  - Near-Infrared Light-Driven Hydrogen Evolution from Water Using a Polypyridyl
      Triruthenium Photosensitizer.
AB  - In order to realize artificial photosynthetic devices for splitting water to H2
      and O2 (2 H2 O+hnu->2 H2 +O2 ), it is desirable to use a wider wavelength range
      of light that extends to a lower energy region of the solar spectrum. Here we
      report a triruthenium photosensitizer [Ru3 (dmbpy)6 (MU-HAT)]6+ (dmbpy=4,4'
      dimethyl-2,2'-bipyridine, HAT=1,4,5,8,9,12-hexaazatriphenylene), which absorbs
      near-infrared light up to 800 nm based on its metal-to-ligand charge transfer (1
      MLCT) transition. Importantly, [Ru3 (dmbpy)6 (MU-HAT)]6+ is found to be the first
      example of a photosensitizer which can drive H2 evolution under the illumination
      of near-infrared light above 700 nm. The electrochemical and photochemical
      studies reveal that the reductive quenching within the ion-pair adducts of [Ru3
      (dmbpy)6 (MU-HAT)]6+ and ascorbate anions affords a singly reduced form of [Ru3
      (dmbpy)6 (MU-HAT)]6+ , which is used as a reducing equivalent in the subsequent
      water reduction process.

PMID- 29034548
TI  - Electroacupuncture alleviates chemotherapy-induced pain through inhibiting
      phosphorylation of spinal CaMKII in rats.
AB  - BACKGROUND: Current medical treatments for chemotherapy-induced pain (CIP) are
      either ineffective or have adverse side effects. Acupuncture may alleviate CIP,
      but its effectiveness against this condition has not been studied. Paclitaxel
      causes neuropathic pain in cancer patients. METHODS: We evaluated the effects of
      electroacupuncture (EA) on paclitaxel-induced CIP in a rat model. Paclitaxel (2
      mg/kg) or vehicle was injected (i.p.) on alternate days of 0-6. The resulting
      pain was treated with 10 Hz/2 mA/0.4 ms pulse EA for 30 min at the equivalent of
      human acupoint GB30 (Huantiao) once every other day between days 14 and 26. For
      sham control, EA needles were inserted into GB30 without stimulation. Von Frey
      filaments with bending forces of 2-8 g and 15 g were used to assess mechanical
      allodynia and hyperalgesia, respectively, on day 13 and once every other day
      between 14-26 days and then for 2-3 weeks after EA treatment. RESULTS: Compared
      to sham control, EA significantly alleviated paclitaxel-induced mechanical
      allodynia and hyperalgesia, as shown by less frequent withdrawal responses to the
      filaments. The alleviation of allodynia/hyperalgesia lasted up to 3 weeks after
      the EA treatment. EA significantly inhibited phosphorylation of Ca2+ /calmodulin
      dependent protein kinase II (CaMKII) in the spinal cord. KN-93, a selective
      inhibitor of p-CaMKII, inhibited mechanical allodynia/hyperalgesia and p-CaMKII.
      5-HT1A receptor antagonist blocked EA inhibition of allodynia/hyperalgesia and p
      CaMKII. CONCLUSIONS: Electroacupuncture activates 5-HT 1A receptors in the spinal
      cord and inhibits p-CaMKII to alleviate both allodynia and hyperalgesia. The data
      support acupuncture/EA as a complementary therapy for CIP. SIGNIFICANCE:
      Electroacupuncture (EA) activates spinal 5-HT1A receptors to inhibit p-CaMKII to
      alleviate paclitaxel-induced pain. Acupuncture/EA may be used as a complementary
      therapy for CIP.

PMID- 29034551
TI  - Early breastfeeding practices: Descriptive analysis of recent Demographic and
      Health Surveys.
AB  - The aim of this study was to describe early breastfeeding practices (initiation
      within 1 hr of birth, no prelacteal feeding, and a combination of both-"optimal"
      early breastfeeding) according to childbirth location in low- and middle-income
      countries. Using data from the most recent Demographic and Health Survey (2000
      2013) for 57 countries, we extracted information on the most recent birth for
      women aged 15-49 with a live birth in the preceding 24 months. Childbirth setting
      was self-reported by location (home or facility) and subtype (home delivery with
      or without a skilled birth attendant; public or private facility). We produced
      overall world and four region-level summary statistics by applying national
      population adjusted survey weights. Overall, 39% of children were breastfed
      within 1 hr of birth (region range 31-60%), 49% received no prelacteal feeding
      (41-65%), and 28% benefited from optimal early breastfeeding (21-46%). In
      South/Southeast Asia and Sub-Saharan Africa, early breastfeeding outcomes were
      more favourable for facility births compared to home births; trends were less
      consistent in Latin America and Middle East/Europe. Among home deliveries, there
      was a higher prevalence of positive breastfeeding practices for births with a
      skilled birth attendant across all regions other than Latin America. For facility
      births, breastfeeding practices were more favourable among those taking place in
      the public sector. This study is the most comprehensive assessment to date of
      early breastfeeding practices by childbirth location. Our results suggest that
      skilled delivery care-particularly care delivered in public sector facilities
      appears positively correlated with favourable breastfeeding practices.

PMID- 29034552
TI  - Cervical carcinomas with a micropapillary component: a clinicopathological study
      of eight cases.
AB  - AIMS: Micropapillary carcinomas, or carcinomas with a micropapillary component,
      are well recognised in the breast and other anatomical sites. However, they have
      seldom been described in the cervix. In this article, we present a
      clinicopathological analysis of eight cervical tumours that showed at least a
      focal (>=5%) component of micropapillary carcinoma. METHODS AND RESULTS: The
      study group comprised eight cervical carcinomas (four adenocarcinomas and four
      adenosquamous carcinomas) with a micropapillary component. The median patient age
      was 41.5 years (range 27-65 years). At presentation, five patients were stage IB,
      two were stage IIB, and one was stage IV. The micropapillary component accounted
      for <=25% of the tumour on initial biopsy or resection specimens in all but one
      case. Immunohistochemistry showed 'inside-out' (reverse polarity) mucin 1
      staining along the cell membrane abutting the stroma. Four patients developed
      metastasis, all of whom showed a pure micropapillary pattern; this led to a
      misdiagnosis of an apparently independent peritoneal serous carcinoma in one
      case. All tumours showed diffuse p16 expression, and all three cases that were
      tested were positive for human papillomavirus (HPV) 18. Three of the six patients
      with at least 12 months of follow-up died of disease, and one is alive with
      distant metastasis. CONCLUSIONS: Usual-type (HPV-related) cervical carcinomas may
      show micropapillary differentiation, usually as a focal finding, and the cells
      show reverse polarity like similar tumours arising in other sites. Micropapillary
      cervical carcinoma appears to be a clinically aggressive malignancy, although
      this needs to be confirmed in larger studies.

PMID- 29034554
TI  - PD1 inhibitors and hair repigmentation: A desirable new side effect.

PMID- 29034553
TI  - Synthesis of Anisotropic Hydrogels and Their Applications.
AB  - Owing to their water-rich structures, which are similar to those of biological
      tissues, hydrogels have long been regarded as promising scaffolds for artificial
      tissues and organs. However, in terms of the structural anisotropy, most
      synthetic hydrogels are substantially different from biological systems.
      Synthetic hydrogels are usually composed of randomly oriented three-dimensional
      polymer networks whereas biological systems adopt anisotropic structures with
      hierarchically integrated building units. Such anisotropic structures often play
      essential roles in biological systems to exhibit particular functions. In this
      context, anisotropic hydrogels provide an entry point for exploring biomimetic
      applications of hydrogels. Reflecting these aspects, an increasing number of
      studies on anisotropic hydrogels have been reported recently. This Minireview
      highlights the use and perspectives of these anisotropic hydrogels, particularly
      focusing on their preparation, structures, and applications.

PMID- 29034555
TI  - Advances and insights into neurological practice 2016-17.

PMID- 29034556
TI  - Silicon Wafers with Facet-Dependent Electrical Conductivity Properties.
AB  - By breaking intrinsic Si (100) and (111) wafers to expose sharp {111} and {112}
      facets, electrical conductivity measurements on single and different silicon
      crystal faces were performed through contacts with two tungsten probes. While Si
      {100} and {110} faces are barely conductive at low applied voltages, as expected,
      the Si {112} surface is highly conductive and Si {111} surface also shows good
      conductivity. Asymmetrical I-V curves have been recorded for the {111}/{112},
      {111}/{110}, and {112}/{110} facet combinations because of different degrees of
      conduction band bending at these crystal surfaces presenting different barrier
      heights to current flow. In particular, the {111}/{110} and {112}/{110} facet
      combinations give I-V curves resembling those of p-n junctions, suggesting a
      novel field effect transistor design is possible capitalizing on the pronounced
      facet-dependent electrical conductivity properties of silicon.

PMID- 29034558
TI  - Adolescent temperament dimensions as stable prospective risk and protective
      factors for salivary C-reactive protein.
AB  - OBJECTIVE: Temperament has associations with later physical health outcomes, yet
      there is a dearth of research exploring the connection between temperament and
      mechanisms that have known associations with these health outcomes. Recent
      research has delineated a connection between personality and inflammation during
      adulthood, but this association has not yet been studied in adolescent samples.
      DESIGN: We investigated whether stable adolescent temperament (averaged over two
      years), specifically effortful control and negative emotionality, provided a more
      robust prediction of inflammation as measured by salivary C-reactive protein
      (sCRP), than depressive symptoms. METHODS: Temperament and depressive symptoms
      were measured in a sample of sixty-three adolescents (37 males) when they were
      approximately 12 years old (mean age = 12.30, SD = 0.69) and again when they were
      approximately 14 years old (mean age = 14.84, SD = 0.49). Levels of sCRP were
      determined approximately 7 months later (mean = 6.77, SD = 2.99) when
      participants were approximately 15 years old (mean age = 15.49, SD = 0.49).
      RESULTS: Regression analyses revealed that effortful control (EC) was
      significantly associated with lower sCRP levels, while higher negative
      emotionality (NE) was significantly associated with higher sCRP levels.
      Furthermore, these associations were larger than those for depressive symptoms
      and were differentially impacted by the addition of covariates. Implications for
      the role of stable risk and protective factors in inflammatory processes are
      discussed. CONCLUSIONS: These findings are the first to show associations between
      adolescent temperament and inflammation. Furthermore, these findings extend
      previous personality research to temperamental research in a younger sample of
      adolescents. Statement of contribution What is already known? There is a large
      extant literature on the association between depressive symptoms and
      inflammation. There is a smaller extant literature on the association between
      personality and inflammation. No studies have examined how adolescent temperament
      traits may relate to inflammation. What does this study add? Longitudinal data
      collection over the course of 3 years in an adolescent sample. Addresses the
      question of whether temperament factors relate to inflammation. Temperament
      provides a more robust predictor of later inflammation than depressive symptoms.

PMID- 29034559
TI  - Healthcare and wider societal implications of stillbirth: a population-based cost
      of-illness study.
AB  - OBJECTIVE: To extend previous work and estimate health and social care costs,
      litigation costs, funeral-related costs, and productivity losses associated with
      stillbirth in the UK. DESIGN: A population-based cost-of-illness study using a
      synthesis of secondary data. SETTING: The National Health Service (NHS) and wider
      society in the UK. POPULATION: Stillbirths occurring within a 12-month period and
      subsequent events occurring over the following 2 years. METHODS: Costs were
      estimated using published data on events, resource use, and unit costs. MAIN
      OUTCOME MEASURES: Mean health and social care costs, litigation costs, funeral
      related costs, and productivity costs for 2 years, reported for a single
      stillbirth and at a national level. RESULTS: Mean health and social care costs
      per stillbirth were L4191. Additionally, funeral-related costs were L559, and
      workplace absence (parents and healthcare professionals) was estimated to cost
      L3829 per stillbirth. For the UK, the annual health and social care costs were
      estimated at L13.6 million, and total productivity losses amounted to L706.1
      million (98% of this cost was attributable to the loss of the life of the baby).
      The figures for total productivity losses were sensitive to the perspective
      adopted about the loss of life of the baby. CONCLUSION: This work expands the
      current intelligence on the costs of stillbirth beyond the health service to
      costs for parents and society, and yet these additional findings must still be
      regarded as conservative estimates of the true economic costs. TWEETABLE
      ABSTRACT: The costs of stillbirth are significant, affecting the health service,
      parents, professionals, and society. PLAIN LANGUAGE SUMMARY: Why and how was the
      study carried out? The personal, social, and emotional consequences of stillbirth
      are profound. Placing a monetary value on such consequences is emotive, yet
      necessary, when deciding how best to invest limited healthcare resources. We
      estimated the average costs associated with a single stillbirth and the costs for
      all stillbirths occurring in the UK over a 1-year period. What were the main
      findings? The average cost to the National Health Service (NHS) of care related
      to the stillbirth and a first subsequent pregnancy was L4191 for each stillbirth.
      For the UK, this cost was L13.6 million annually. Clinical negligence payments to
      bereaved parents were estimated at L2.5 million per year. Parents were estimated
      to spend L1.8 million per year on funerals. The cost of workplace absence as
      parents cope with the effects of grief was estimated at L2476 per stillbirth. For
      the UK, this cost was L8.1 million annually. The loss of a baby is also the loss
      of an individual with the potential to become a valued and productive member of
      society. The expected value of an adult's lifetime working hours was taken as an
      estimate of this productivity loss, and was L213,304 for each stillbirth. The
      annual cost for all stillbirths was L694 million. We know from parents that the
      birth of a subsequent child in no way replaces a stillborn baby. We found that
      52% of women fall pregnant within 12 months of a stillbirth. From a purely
      economic perspective concerned only with the number of individuals in society,
      babies born during this period could potentially replace the productivity losses
      of the stillborn baby. Adopting this approach, which we understand is
      controversial and difficult for bereaved parents, the expected productivity
      losses would be lower, at L333 million. What are the limitations of the work? For
      some categories, existing data were unavailable and we used clinical opinion to
      estimate costs. Furthermore, we were unable to quantify some indirect
      consequences, for example the psychological distress experienced by wider family
      members. What is the implication for parents? Placing a monetary value on what is
      for parents a profound personal tragedy may seem unkind. It is, however,
      unavoidable if we are to provide policy makers with vital information on the wide
      ranging consequences that could be prevented through future investments in
      initiatives to reduce stillbirth.

PMID- 29034561
TI  - Reduction of a Cerium(III) Siloxide Complex To Afford a Quadruple-Decker Arene
      Bridged Cerium(II) Sandwich.
AB  - Organometallic multi-decker sandwich complexes containing f-elements remain rare,
      despite their attractive magnetic and electronic properties. The reduction of the
      CeIII siloxide complex, [KCeL4 ] (1; L=OSi(OtBu)3 ), with excess potassium in a
      THF/toluene mixture afforded a quadruple-decker arene-bridged complex, [K(2.2.2
      crypt)]2 [{(KL3 Ce)(MU-eta6 :eta6 -C7 H8 )}2 Ce] (3). The structure of 3 features
      a [Ce(C7 H8 )2 ] sandwich capped by [KL3 Ce] moieties with a linear arrangement
      of the Ce ions. Structural parameters, UV/Vis/NIR data, and DFT studies indicate
      the presence of CeII ions involved in delta bonding between the Ce cations and
      toluene dianions. Complex 3 is a rare lanthanide multi-decker complex and the
      first containing non-classical divalent lanthanide ions. Moreover, oxidation of 1
      by AgOTf (OTf=O3 SCF3 ) yielded the CeIV complex, [CeL4 ] (2), showing that
      siloxide ligands can stabilize Ce in three oxidation states.

PMID- 29034560
TI  - Estimation of a significance threshold for epigenome-wide association studies.
AB  - Epigenome-wide association studies (EWAS) are designed to characterise population
      level epigenetic differences across the genome and link them to disease. Most
      commonly, they assess DNA-methylation status at cytosine-guanine dinucleotide
      (CpG) sites, using platforms such as the Illumina 450k array that profile a
      subset of CpGs genome wide. An important challenge in the context of EWAS is
      determining a significance threshold for declaring a CpG site as differentially
      methylated, taking multiple testing into account. We used a permutation method to
      estimate a significance threshold specifically for the 450k array and a
      simulation extrapolation approach to estimate a genome-wide threshold. These
      methods were applied to five different EWAS datasets derived from a variety of
      populations and tissue types. We obtained an estimate of alpha=2.4*10-7 for the
      450k array, and a genome-wide estimate of alpha=3.6*10-8. We further demonstrate
      the importance of these results by showing that previously recommended sample
      sizes for EWAS should be adjusted upwards, requiring samples between ~10% and
      ~20% larger in order to maintain type-1 errors at the desired level.

PMID- 29034562
TI  - Canine central corneal thickness measurements via Pentacam-HR(r) , optical
      coherence tomography (Optovue iVue(r) ), and high-resolution ultrasound
      biomicroscopy.
AB  - OBJECTIVE: To compare central corneal thickness (CCT) values in canine eyes using
      Pentacam-HR(r) Scheimpflug imaging (Pentacam), Optovue(r) iVue spectral-domain
      optical coherence tomography (SD-OCT), and high-resolution ultrasound
      biomicroscopy (UBM) and generate normative canine Pentacam CCT values. ANIMALS
      STUDIED: Twenty-four client-owned dogs (37 eyes) with nondiseased cornea(s)
      presenting to the Colorado State University Veterinary Teaching Hospital.
      PROCEDURES: Corneal images were acquired via Pentacam, SD-OCT, and UBM in the
      listed order. Machine-calculated values of CCT from Pentacam and SD-OCT were
      compared to operator-measured values from UBM. Bland-Altman analysis was
      performed to evaluate agreement between instruments. RESULTS: Mean CCT +/- SD
      measured by Pentacam was 629.73 +/- 64.57 MUm, by SD-OCT was 610.56 +/- 57.48
      MUm, and by UBM was 689.77 +/- 55.93 MUm. On average, Pentacam CCT was 19.17 +/-
      32.90 MUm (3%) thicker than SD-OCT and 65.12 +/- 44.52 MUm (10.3%) thinner than
      UBM. SD-OCT was on average 82.47 MUm (13.5% ) thinner than UBM. The 95% limits of
      agreement were (-45.31, 83.65), (-152.38, 22.13), and (-126.674, -38.270) for
      Pentacam vs. SD-OCT, Pentacam vs. UBM, and SD-OCT vs. UBM respectively. All
      differences were statistically significant (P < 0.01). CONCLUSIONS: Considering
      there is an average of 7.5% normal diurnal variation in canine CCT, a 3.0%
      difference between Pentacam and SD-OCT values is likely not clinically relevant.
      However, Pentacam measurements were both statistically and clinically
      significantly different from UBM and SD-OCT measurements.

PMID- 29034563
TI  - Heart failure study of multipoint pacing effects on ventriculoarterial coupling:
      Rationale and design of the HUMVEE trial.
AB  - Cardiac resynchronization therapy (CRT) is an established therapy for symptomatic
      heart failure (HF). Unfortunately, many recipients remain nonresponders. Studies
      have revealed the potential role of multipoint pacing (MPP) in improving response
      and outcomes. The aim of this study is to compare the effects of MPP against
      those of standard biventricular pacing (BVP) on (i) ventriculoarterial coupling
      (VAC) and energy efficiency of the failing heart, (ii) diastolic function, (iii)
      quality of life, and (iv) NT-proBNP levels and glomerular filtration rate (GFR)
      during a follow-up of 13 months. HUMVEE is a single-center, prospective,
      observational, crossover cohort study. Seventy-six patients with BVP indication
      will be implanted with a system able to deliver both pacing modes. BVP will be
      activated at implantation and optimized 1 month after. At 6 months
      postoptimization MPP will be activated and optimized. Optimization will be
      performed based on stroke volume maximization, as assessed by ultrasound.
      Laboratory measurements (GFR and NT-proBNP) and echocardiographic studies (VAC
      calculation, strain rate, diastolic function) will be performed at implantation,
      6 months post-BVP optimization and at the end of 13 months of follow-up (6 months
      post-MPP optimization). Potential reduction in arrhythmogenesis by MPP will also
      be assessed. MPP is a pacing modality with the potential to improve HF patients'
      outcomes. The HUMVEE trial will attempt to associate any potential added
      beneficial effects of MPP over standard BVP with alterations in VAC and energy
      efficiency of the heart, thus uncovering a novel mechanistic link between MPP and
      improved outcomes in HF.

PMID- 29034564
TI  - A report from #BlueJC: Would you recommend cranberry capsules to prevent
      postoperative bacteriuria?

PMID- 29034565
TI  - Shifts of growing-season precipitation peaks decrease soil respiration in a
      semiarid grassland.
AB  - Changing precipitation regimes could have profound influences on carbon (C) cycle
      in the biosphere. However, how soil C release from terrestrial ecosystems
      responds to changing seasonal distribution of precipitation remains unclear. A
      field experiment was conducted for 4 years (2013-2016) to examine the effects of
      altered precipitation distributions in the growing season on soil respiration in
      a temperate steppe in the Mongolian Plateau. Over the 4 years, both advanced and
      delayed precipitation peaks suppressed soil respiration, and the reductions
      mainly occurred in August. The decreased soil respiration could be primarily
      attributable to water stress and subsequently limited plant growth (community
      cover and belowground net primary productivity) and soil microbial activities in
      the middle growing season, suggesting that precipitation amount in the middle
      growing season is more important than that in the early, late, or whole growing
      seasons in regulating soil C release in grasslands. The observations of the
      additive effects of advanced and delayed precipitation peaks indicate semiarid
      grasslands will release less C through soil respiratory processes under the
      projected seasonal redistribution of precipitation in the future. Our findings
      highlight the potential role of intra-annual redistribution of precipitation in
      regulating ecosystem C cycling in arid and semiarid regions.

PMID- 29034566
TI  - Activation and Deactivation of Gold/Ceria-Zirconia in the Low-Temperature Water
      Gas Shift Reaction.
AB  - Gold (Au) on ceria-zirconia is one of the most active catalysts for the low
      temperature water-gas shift reaction (LTS), a key stage of upgrading H2 reformate
      streams for fuel cells. However, this catalyst rapidly deactivates on-stream and
      the deactivation mechanism remains unclear. Using stop-start scanning
      transmission electron microscopy to follow the exact same area of the sample at
      different stages of the LTS reaction, as well as complementary X-ray
      photoelectron spectroscopy, we observed the activation and deactivation of the
      catalyst at various stages. During the heating of the catalyst to reaction
      temperature, we observed the formation of small Au nanoparticles (NPs; 1-2 nm)
      from subnanometer Au species. These NPs were then seen to agglomerate further
      over 48 h on-stream, and most rapidly in the first 5 h when the highest rate of
      deactivation was observed. These findings suggest that the primary deactivation
      process consists of the loss of active sites through the agglomeration and
      possible dewetting of Au NPs.

PMID- 29034567
TI  - Timeframe of socket cortication after tooth extraction: A retrospective
      radiographic study.
AB  - OBJECTIVES: To assess the timeframe between tooth extraction and radiographically
      detectable socket cortication in humans. METHODS: Two hundred and fifty patients
      with a CT scan <=36 months after tooth extraction were included. First, three
      orthoradial multiplanar reconstruction slices, representing the major part of the
      extraction socket, were scored regarding the degree of bone healing as (i)
      healed, that is, complete/continuous cortication of the socket entrance, or (ii)
      non-healed. Thereafter, based on the results of all three slices, the stage of
      cortication of the extraction socket, as one unit, was classified as (i) non
      corticated, that is, all three slices judged as non-healed, (ii) partially
      corticated, that is, 1 or 2 slices judged as non-healed, or (iii) completely
      corticated, that is, all three slices judged as healed. The possible effect of
      several independent parameters, that is, age, gender, timeframe between tooth
      extraction and CT scan, tooth type, extent of radiographic bone loss of the
      extracted tooth, tooth-gap type, smoking status, presence of any systemic
      disease, and medication intake, on cortication status was statistically
      evaluated. RESULTS: Three to 6 months after tooth extraction, 27% of the sockets
      were judged as non-corticated and 53% were judged as partially corticated. After
      9-12 months, >80% of the sockets were corticated, while some incompletely
      corticated sockets were detected up to 15 months after extraction. Each
      additional month after tooth extraction contributed significantly to a higher
      likelihood of a more advanced stage of cortication, while radiographic bone loss
      >=75% significantly prolonged cortication time; no other independent variable had
      a significant effect. CONCLUSIONS: The results indicate a considerably long
      timeframe until complete cortication of an extraction socket, that is, 3-6 months
      after tooth extraction 3 of 4 sockets were still not completely corticated, and
      only after 9-12 months, complete cortication was observed in about 80% of the
      sockets.

PMID- 29034568
TI  - Innovation not recovery: dynamic redox promotes metazoan radiations.
AB  - Environmental fluctuations in redox may reinforce rather than hinder evolutionary
      transitions, such that variability in near-surface oceanic oxygenation can
      promote morphological evolution and novelty. Modern, low-oxygen regions are
      heterogeneous and dynamic habitats that support low diversity and are inhabited
      by opportunistic and non-skeletal metazoans. We note that several major radiation
      episodes follow protracted or repeating intervals (>1 million years) of
      persistent and dynamic shallow marine redox (oceanic anoxic events). These are
      also often associated with short-lived mass-extinction events (<0.5 million
      years) where skeletal benthic incumbents are removed, and surviving or newly
      evolved benthos initially inhabit transient oxic habitats. We argue that such
      intervals create critical opportunities for the generation of evolutionary
      novelty, followed by innovation and diversification. We develop a general model
      for redox controls on the distribution and structure of the shallow marine
      benthos in a dominantly anoxic world, and compile data from the terminal
      Ediacaran-mid-Cambrian (~560-509 Ma), late Cambrian-Ordovician (~500-445 Ma), and
      Permo-Triassic (~255-205 Ma) to test these predictions. Assembly of phylogenetic
      data shows that prolonged and widespread anoxic intervals indeed promoted
      morphological novelty in soft-bodied benthos, providing the ancestral stock for
      subsequently skeletonized lineages to appear as innovations once oxic conditions
      became widespread and stable, in turn promoting major evolutionary
      diversification. As a result, we propose that so-called 'recovery' intervals
      after mass extinctions might be better considered as 'innovation' intervals.

PMID- 29034569
TI  - Gold-Doping of Double-Crown Pd Nanoclusters.
AB  - Double-crown Ni, Pd, or Pt nanoclusters have attracted extensive interests due to
      their aesthetic structure and intriguing properties. However, their doping by
      other metals remains unknown until now. Herein, Pd4 (PET)8 and Pd5 (PET)10 (PET:
      SCH2 CH2 Ph) were successfully doped with gold and the doped nanoclusters were
      characterized by using multiple techniques such as mass spectrometry and X-ray
      crystallography. It is revealed that in the doping not one but two gold atoms
      replace one Pd with the other double-crown structure essentially unchanged, and
      the gold-doping results in the blue-shift of the maximum visible absorption, the
      increase of optical energy gap and the reduction of anti-aromaticity of monometal
      Pd nanoclusters. Importantly, it is found that Au4 Pd2 (PET)8 nanocluster bears
      chirality originating from not only the helixed Au4 Pd2 S8 framework, but also
      unanimous R or S configuration of sulfur atoms in the enantiomer. For the latter
      chirality origin, it was not previously reported or proposed. Au4 Pd2 (PET)8
      reported here also represents the smallest chiral bimetal nanocluster so far to
      the best of our knowledge. This work advances one step toward both the tailoring
      of group 10 metal nanoclusters by doping and the understanding of chirality
      origin for metal nanoclusters.

PMID- 29034570
TI  - Efficacy of different carriers for the triple antibiotic powder during
      regenerative endodontic procedures.
AB  - Chemical debridement during Regenerative Endodontic procedures is important.
      Previous research studies have evaluated various antibiotics and their
      concentrations but none have addressed the concern of delivering these materials.
      Hence, the purpose of this study was to determine what carrier could be used
      effectively in a clinical setting. Sixty caries-free maxillary incisors were used
      and inoculated with Enterococcus faecalis and divided into positive and
      irrigation controls and experimental groups that had triple antibiotic powder
      (1:1:1 ciprofloxacin:metronidazole:minocycline) delivered using various carriers:
      saline, cotton, sponge and methylcellulose. Current AAE regenerative protocols
      were followed. S2 sampling was performed and tested for bacterial presence via
      culturing and SEM. The results demonstrated that saline was the most effective
      carrier for the triple antibiotic powder while cotton and sponge were most
      ineffective. Saline and methylcellulose both reduced bacterial counts to a
      significant level. Overall, this study demonstrated that saline as a carrier was
      most effective and should be routinely used.

PMID- 29034572
TI  - Epidemiology and molecular characterization of Porcine teschovirus in Hunan,
      China.
AB  - Porcine teschoviruses (PTVs) have been shown to be widely distributed in pig
      populations. In this study, 261 faecal and 91 intestinal content samples
      collected from pigs at 29 farms in Hunan, China, were tested for the presence of
      PTV by reverse transcription-polymerase chain reaction (RT-PCR). An overall PTV
      positivity rate of 19.03% was detected by RT-PCR, and a high PTV infection rate
      was circulating in asymptomatic fattening and nursery pigs. In total, 40 PTV
      isolates (PTV-HuNs) were obtained. Alignment of their coding sequences with those
      of other known PTVs revealed that the genomic sequence of the polyprotein
      contains 6,606-6,621 nucleotides, encoding a 2,202-2,207-amino acid sequence.
      Phylogenetic analyses based on the VP1 gene and capsid protein gene exhibited 13
      main lineages corresponding to PTV serotypes 1-13, and seven PTV serotypes (PTV 2
      6, 9, and 11) were identified in the isolates obtained in our study; this is the
      first report of PTV 5, 9 and 11 in China. Recombination analysis among the PTV
      HuNs indicated that nine recombination events have occurred, including both inter
      and intraserotype events. In addition, results demonstrated that only limited
      positive selection is acting on the global population of PTV isolates, and
      purifying selection is predominant. In conclusion, this study revealed a high
      infection rate of PTVs circulating in asymptomatic fattening and nursery pigs.
      The 40 PTV-HuNs showed high genetic diversity, and genetic analysis of all
      available PTV sequences revealed that strong purifying selection and
      recombination play important roles in the genetic diversity and evolution of the
      virus.

PMID- 29034573
TI  - Memory encoding-related anterior hippocampal potentials are modulated by deep
      brain stimulation of the entorhinal area.
AB  - BACKGROUND: Deep brain stimulation (DBS) of the human entorhinal area using 50 Hz
      pulses has revealed conflicting results regarding memory performance. Moreover,
      its impact on memory-related hippocampal potentials has not yet been
      investigated. METHODS: We recorded data from seven epilepsy patients implanted
      with depth electrodes in the entorhinal cortex, hippocampus, amygdala, and
      parahippocampal cortex. Entorhinal DBS (bipolar, biphasic 50 Hz pulses, on- and
      off-cycles of 15 s) was applied with low amplitude (0.1 mA) to resemble
      physiologic conditions. During DBS on- and off-periods, patients learned noun
      color associations that were later tested. RESULTS: During entorhinal DBS we
      observed more positive deflections of event-related potentials (ranging from 700
      to 950 ms) in the anterior hippocampus for the on- vs. off-condition. We detected
      no effects in the amygdala, mid hippocampus and parahippocampal cortex. On the
      behavioral level, no differences in memory performance (item and source memory)
      were apparent in the on- vs. off-condition, neither across all trials nor across
      patients. DISCUSSION: Our findings indicate that entorhinal DBS with low
      amplitude has an impact on memory encoding-related potentials within the anterior
      hippocampus, but not on memory performance per se.

PMID- 29034571
TI  - Association between subclinical thyroid dysfunction and change in bone mineral
      density in prospective cohorts.
AB  - BACKGROUND: Subclinical hyperthyroidism (SHyper) has been associated with
      increased risk of hip and other fractures, but the linking mechanisms remain
      unclear. OBJECTIVE: To investigate the association between subclinical thyroid
      dysfunction and bone loss. METHODS: Individual participant data analysis was
      performed after a systematic literature search in MEDLINE/EMBASE (1946-2016). Two
      reviewers independently screened and selected prospective cohorts providing
      baseline thyroid status and serial bone mineral density (BMD) measurements. We
      classified thyroid status as euthyroidism (thyroid-stimulating hormone [TSH] 0.45
      4.49 mIU/L), SHyper (TSH < 0.45 mIU/L) and subclinical hypothyroidism (SHypo, TSH
      >= 4.50-19.99 mIU/L) both with normal free thyroxine levels. Our primary outcome
      was annualized percentage BMD change (%DeltaBMD) from serial dual X-ray
      absorptiometry scans of the femoral neck, total hip and lumbar spine, obtained
      from multivariable regression in a random-effects two-step approach. RESULTS:
      Amongst 5458 individuals (median age 72 years, 49.1% women) from six prospective
      cohorts, 451 (8.3%) had SHypo and 284 (5.2%) had SHyper. During 36 569 person
      years of follow-up, those with SHyper had a greater annual bone loss at the
      femoral neck versus euthyroidism: %DeltaBMD = -0.18 (95% CI: -0.34, -0.02; I2 =
      0%), with a nonstatistically significant pattern at the total hip: %DeltaBMD = 
      0.14 (95% CI: -0.38, 0.10; I2 = 53%), but not at the lumbar spine: %DeltaBMD =
      0.03 (95% CI: -0.30, 0.36; I2 = 25%); especially participants with TSH < 0.10
      mIU/L showed an increased bone loss in the femoral neck (%Delta BMD = -0.59; [95%
      CI: -0.99, -0.19]) and total hip region (%DeltaBMD = -0.46 [95% CI: -1.05, 
      0.13]). In contrast, SHypo was not associated with bone loss at any site.
      CONCLUSION: Amongst adults, SHyper was associated with increased femoral neck
      bone loss, potentially contributing to the increased fracture risk.

PMID- 29034574
TI  - Morphometric and histologic characterization of alveolar bone from hypertensive
      patients.
AB  - BACKGROUND: Hypertension is considered a risk factor in implant dentistry but the
      underlying reasons remain unclear. It may be that hypertension has a negative
      impact on the local bone quality. PURPOSE: Here we evaluated the structural and
      histological parameters of bone collected from hypertensive patients treated by
      antagonists of the renin-angiotensin system, and of bone collected from
      normotensive patients. MATERIAL AND METHODS: A total of 30 patients were referred
      for rehabilitation with dental implants to be placed in the posterior mandible.
      The first group were hypertensive patients treated with RAS antagonists. The
      second group were normotensive patients not taking medication. Bone biopsies
      collected during implant installation were subjected to analysis. Micro CT
      revealed the structural parameters. Histological analyses together with
      immunohistochemical staining of osteogenic markers were performed. RESULTS: The
      structural parameters of bone volume, trabecular thickness, trabecular number,
      separation of the trabecular, and total porosity were similar between the 2
      groups (P > .05). The histological appearance of bone derived from hypertensive
      patients was normal. The staining pattern of Runx-2, osteopontin, and osteocalcin
      were comparable in both groups. CONCLUSIONS: These observations suggest that
      hypertensive patients treated with renin-angiotensin system antagonists have
      regular alveolar bone with respect to bone structure and histological parameters.

PMID- 29034575
TI  - Life after prostate cancer: A systematic literature review and thematic synthesis
      of the post-treatment experiences of Black African and Black Caribbean men.
AB  - Evidence shows that there are significant ethnic variations in prostate cancer
      prevalence and outcomes. Specifically, Black African and Black Caribbean men may
      encounter different post-treatment experiences than Caucasian men due to their
      disproportionately higher risk of being diagnosed with advanced prostate cancer.
      But to date, no review of these experiences has been undertaken. This review
      synthesised findings from existing literature on the post-treatment experiences
      of Black African and Black Caribbean men with prostate cancer and identified
      pertinent issues which may be useful to inform practice and future research.
      Seven databases were systematically searched using developed search terms. Four
      qualitative studies were identified and critically appraised. Findings are
      summarised under four main themes: symptom experience, healthcare experience,
      marital and social relationships and coping strategies. Cultural definitions of
      masculinity influenced the meanings men gave to their post-treatment experiences.
      While men's experiences of healthcare varied, the provision of professional
      support to address their post-treatment distress was lacking. Men derived most
      support from wives, peers and church communities. A culturally sensitive approach
      which recognises diversity among Black African and Black Caribbean populations
      and treats individuals within their religious and socio-cultural contexts could
      potentially improve men's post-treatment experiences. Areas for further research
      were also identified.

PMID- 29034576
TI  - Substantial Variability Across Individuals in the Vascular and Nutrigenomic
      Response to an Acute Intake of Curcumin: A Randomized Controlled Trial.
AB  - SCOPE: Curcumin exerts biological activities of interest in cardiovascular
      prevention. However, its vascular protective effect is still poorly investigated
      in humans. The present study aims to assess vascular effect of an acute intake of
      curcumin and its nutrigenomic impact in circulating immune cells. METHODS AND
      RESULTS: In a randomized, double-blind, crossover design, 18 healthy smokers
      consume a placebo or a 5-g curcumin. Before and 2 h after the intake, vascular
      function measurements are performed by using flow-mediated dilation (FMD). In
      addition, endothelial function in the microcirculation and blood pressure are
      evaluated. Plasma curcumin concentrations and changes in gene expression in
      peripheral blood mononuclear cells (PBMC) are analyzed. No significant effect of
      curcumin on FMD is observed when considering the entire study population, mainly
      due to a high interindividual variability. A subgroup analysis according to the
      gender or the cardiovascular-risk score reveals a significant effect of curcumin
      on FMD in women and in subjects presenting lower cardiovascular risk. No change
      in gene expression is observed when data are analyzed for all volunteers but
      changes in expression are observed when analyzed according to gender.
      CONCLUSIONS: This clinical trial highlights that a substantial variability in
      efficacy of curcumin exists across individuals.

PMID- 29034577
TI  - Untargeted GC-MS Metabolomics Reveals Changes in the Metabolite Dynamics of
      Industrial Scale Batch Fermentations of Streptoccoccus thermophilus Broth.
AB  - An industrial scale biomass production using batch or fed-batch fermentations
      usually optimized by selection of bacterial strains, tuning fermentation media,
      feeding strategy, and temperature. However, in-depth investigation of the biomass
      metabolome during the production may reveal new knowledge for better
      optimization. In this study, for the first time, the authors investigated seven
      fermentation batches performed on five Streptoccoccus thermophilus strains during
      the biomass production at Chr. Hansen (Denmark) in a real life large scale
      fermentation process. The study is designed to investigate effects of batch
      fermentation, fermentation time, production line, and yeast extract brands on the
      biomass metabolome using untargeted GC-MS metabolomics. Processing of the raw GC
      MS data using PARAFAC2 revealed a total of 90 metabolites out of which 64 are
      identified. Partitioning of the data variance according to the experimental
      design was performed using ASCA and revealed that batch and fermentation time
      effects and their interaction term were the most significant effects. The yeast
      extract brand had a smaller impact on the biomass metabolome, while the
      production line showed no effect. This study shows that in-depth metabolic
      analysis of fermentation broth provides a new tool for advanced optimization of
      high-volume-low-cost biomass production by lowering the cost, increase the yield,
      and augment the product quality.

PMID- 29034578
TI  - A prospective, split-mouth study comparing tilted implants with angulated
      connection versus conventional implants with angulated abutment.
AB  - BACKGROUND: An angulation of the implant connection could overcome the problems
      related to angulated abutments. PURPOSE: This study compares conventional
      implants with angulated abutment to tilted implants with an angulated connection.
      MATERIALS AND METHODS: Twenty patients were treated in the edentulous mandible.
      In the posterior jaw locations, one conventional tilted implant with angulated
      abutment and one angulated implant without abutment were placed. In the anterior
      jaw, two conventional implants were placed, one with and one without abutment.
      Implants were immediately loaded and 3 months later, the final bridge (PFM or
      monolithic zirconia) was placed. RESULTS: After a follow-up of 48 months, 17
      patients were available for clinical examination. The mean overall marginal bone
      loss (MBL) was 1.26 mm. No significant differences in implant survival, MBL,
      periodontal indices, patients' satisfaction, or complications was found between
      implants restored on abutment or implant level, between the posteriorly located
      angulated implant nor angulated abutment, and between both anterior implants with
      or without abutment. The posterior implants demonstrated less MBL compared to the
      anterior implants (P < .001). There was no significant difference in MBL between
      the implants restored with zirconia or PFM bridges (P = .294). Overall mean
      pocket depth was 2.83 mm. More plaque was found in the PFM group compared to the
      full-zirconia group, at the bridge (P = .042) and the implants (P = .029). There
      was no difference between both materials in pocket depth (P = .635) or bleeding
      (P = .821). One zirconia bridge fractured, two angulated abutment were replaced
      and four loose bridge screws connected to the angulated abutments had to be
      tightened. Patients were overall satisfied (4.74/5). CONCLUSION: An implant with
      angulated connection may results in a stronger connection but does not affect the
      marginal bone loss. No difference in MBL was seen between implants restored on
      abutment or implant level. Zirconia seems to reduce the amount of plaque.

PMID- 29034579
TI  - Rotary versus reciprocating shaping files in bacterial elimination from long oval
      canals.
AB  - A comparison of the abilities of rotary versus reciprocating files to eliminate
      viable Enterococcus faecalis populations from the long oval root canals of
      extracted human teeth. Fifty teeth were contaminated and randomly distributed
      into two groups (n = 25 each): BT-RaCe group and WaveOne group. Two microbial
      samples were obtained from each tooth before (S1) and after (S2) instrumentation.
      The CFUs from the S1 and S2 measurements were calculated and compared between the
      groups. Both groups showed significantly fewer CFUs in the S2 samples (P <
      0.001). In the S2 intragroup comparison, BT-RaCe resulted in significantly fewer
      CFUs than WaveOne (P = 0.010). In the direct comparison between the rotary
      multiple file shaping system and the reciprocating single-file system, the
      multiple file system was more efficient at reducing the microbiological load of
      viable E. faecalis from long oval root canals.

PMID- 29034580
TI  - Selective inhibition of TRPM2 channel by two novel synthesized ADPR analogues.
AB  - Transient receptor potential melastatin-2 (TRPM2) channel critical for monitoring
      internal body temperature is implicated in the pathological processes such as
      neurodegeneration. However, lacking selective and potent TRPM2 inhibitors impedes
      investigation and validation of the channel as a drug target. To discover novel
      and selective TRPM2 inhibitors, a series of adenosine 5'-diphosphoribose
      analogues were synthesized, and their activities and selectivity were evaluated.
      Whole-cell patch-clamp recordings were employed for screen and evaluation of
      synthesized compounds. Two compounds, 7i and 8a, were identified as TRPM2
      inhibitors with IC50 of 5.7 and 5.4 MUm, respectively. Both 7i and 8a inhibited
      TRPM2 current without affecting TRPM7, TRPM8, TRPV1 and TRPV3. These two TRPM2
      inhibitors can serve as new pharmacological tools for further investigation and
      validation of TRPM2 channel as a drug target, and the summarized structure
      activity relationship (SAR) may also provide insights into further improving
      existing inhibitors as potential lead compounds.

PMID- 29034581
TI  - A novel single nucleotide deletion mutation in exon 2 (HBB: c240delC) of beta
      globin gene: A case report.

PMID- 29034582
TI  - Detection of Brucella abortus B19 strain DNA in seminal plasma by polymerase
      chain reaction in Brazil.
AB  - A total of 27 seminal plasma samples from cattle-breeding farms or semen centres
      located in Minas Gerais, Brazil, previously negative by serological and tested
      positive for Brucella spp. with primer specific for the amplification of the gene
      virb5 by polymerase chain reaction (PCR) were analysed for the detection of
      Brucella abortus DNA by PCR. It was found that nine samples (33.33%) contained B.
      abortus B19 strain DNA, two (7.40%) contained B. abortus DNA and five (18.51%)
      contained both DNA. The larger number of samples with B. abortus B19 strain DNA
      would explained by the environmental contamination by vaccinated females with
      persistent excretion or some illegal vaccination process. It is first reported of
      male bovines detected with both DNA.

PMID- 29034583
TI  - The effect of head-up tilt upon markers of heart rate variability in patients
      with atrial fibrillation.
AB  - BACKGROUND: Heart rate variability (HRV) analysis is uncommonly undertaken in
      patients with atrial fibrillation (AF) due to an assumption that ventricular
      response is random. We sought to determine the effects of head-up tilt (HUT), a
      stimulus known to elicit an autonomic response, on HRV in patients with AF; we
      contrasted the findings with those of patients in sinus rhythm (SR). METHODS:
      Consecutive, clinically indicated tilt tests were examined for 207 patients: 176
      in SR, 31 in AF. Patients in AF were compared to an age-matched SR cohort (n =
      69). Five minute windows immediately before and after tilting were analyzed using
      time-domain, frequency-domain and nonlinear HRV parameters. Continuous,
      noninvasive assessment of blood pressure, heart rate and stroke volume were
      available in the majority of patients. RESULTS: There were significant
      differences at baseline in all HRV parameters between AF and age matched SR. HUT
      produced significant hemodynamic changes, regardless of cardiac rhythm.
      Coincident with these hemodynamic changes, patients in AF had a significant
      increase in median [quartile 1, 2] DFA-alpha2 (+0.14 [-0.03, 0.32], p < .005) and
      a decrease in sample entropy (-0.17 [-0.50, -0.01], p < .005). CONCLUSION: In the
      SR cohort, increasing age was associated with fewer HRV changes on tilting.
      Patients with AF had blunted HRV responses to tilting, mirroring those seen in an
      age matched SR group. It is feasible to measure HRV in patients with AF and the
      changes observed on HUT are comparable to those seen in patients in sinus rhythm.

PMID- 29034585
TI  - Corrigendum.

PMID- 29034586
TI  - Avoiding Internal Capsule Stimulation With a New Eight-Channel Steering Deep
      Brain Stimulation Lead.
AB  - OBJECTIVE: Novel deep brain stimulation (DBS) lead designs are currently entering
      the market, which are hypothesized to provide a way to steer the stimulation
      field away from neural populations responsible for side effects and towards
      populations responsible for beneficial effects. The objective of this study is to
      assess the performances of a new eight channel steering-DBS lead and compare this
      with a conventional cylindrical contact (CC) lead. APPROACH: The two leads were
      evaluated in a finite element electric field model combined with multicompartment
      neuron and axon models, representing the internal capsule (IC) fibers and
      subthalamic nucleus (STN) cells. We defined the optimal stimulation setting as
      the configuration that activated the highest percentage of STN cells, without
      activating any IC fibers. With this criterion, we compared monopolar stimulation
      using a single contact of the steering-DBS lead and CC lead, on three locations
      and four orientations of the lead. In addition, we performed a current steering
      test case by dividing the current over two contacts with the steering-DBS lead in
      its worst-case orientation. MAIN RESULTS: In most cases, the steering-DBS lead is
      able to stimulate a significantly higher percentage of STN cells compared to the
      CC lead using single contact stimulation or using a two contact current steering
      protocol when there is approximately a 1 mm displacement of the CC lead. The
      results also show that correct placement and orientation of the lead in the
      target remains an important aspect in achieving the optimal stimulation outcome.
      SIGNIFICANCE: Currently, clinical trials are set up in Europe with a similar
      design as the steering-DBS lead. Our results illustrate the importance of the
      orientation of the new steering-DBS lead in avoiding side effects induced by
      stimulation of IC fibers. Therefore, in clinical trials sufficient attention
      should be paid to implanting the steering DBS-lead in the most effective
      orientation.

PMID- 29034587
TI  - Open Fluidics: A Cell Culture Flow System Developed Over Wettability Contrast
      Based Chips.
AB  - Biological tissues are recurrently exposed to several dynamic mechanical forces
      that influence cell behavior. On this work, the focus is on the shear stress
      forces induced by fluid flow. The study of flow-induced effects on cells leads to
      important advances in cardiovascular, cancer, stem cell, and bone biology
      understanding. These studies are performed using cell culture flow (CCF) systems,
      mainly parallel plate flow chambers (PPFC), and microfluidic systems. Here, it is
      proposed an original CCF system based on the open fluidics concept. The system is
      developed using a planar superhydrophobic platform with hydrophilic paths. The
      paths work as channels to drive cell culture medium flows without using walls for
      liquid confinement. The liquid streams are controlled just based on the
      wettability contrast. To validate the concept, the effect of the shear stress
      stimulus in the osteogenic differentiation of C2C12 myoblast cells is studied.
      Combining bone morphogenic protein (specifically BMP-2) stimulation with this
      mechanical stimulus, a synergistic effect is found on osteoblast differentiation.
      This effect is confirmed by the enhancement of alkaline phosphatase activity, a
      well-known early marker of osteogenic differentiation. The suggested CCF system
      combines characteristics and advantages of both the PPFC and microfluidic
      systems.

PMID- 29034588
TI  - Clinical and demographic differences between patients with manic, depressive and
      schizophrenia-spectrum psychoses presenting to Early Intervention Services in
      London.
AB  - AIM: To investigate the relationship between the presenting clinical and
      demographic characteristics in first-episode psychosis (FEP) patients with their
      clinical diagnostic grouping 1 year later. METHODS: Data from 1014 first
      presentation psychosis patients from seven London-based Early Intervention
      Services were extracted from the MiData audit database. Associations between
      clinical and demographic measures at presentation and clinical diagnosis made at
      1 year were assessed with analysis of variance (ANOVA) and Chi-square tests.
      RESULTS: The sample comprised 76% of patients with schizophrenia-spectrum
      diagnoses, 9% with manic psychoses (MP) and 6% with depressive psychoses.
      Compared to the other 2 groups, patients who were diagnosed as having MP were
      younger, with higher education and shorter duration of untreated psychosis, and
      had higher Young Mania Rating Scale scores at presentation and lower Positive and
      Negative Syndrome Scale (PANSS) negative scores. Patients diagnosed at 1 year as
      having depressive psychosis were older and more likely to be white, with the
      lowest PANSS positive scores at baseline. Patients diagnosed at 1 year as having
      schizophrenia spectrum diagnoses were more likely to be males. Patients in the 3
      diagnostic subgroups of psychosis differed on both clinical and demographic
      characteristics at presentation. CONCLUSIONS: There were significant clinical and
      demographic differences at presentation between FEP patients who received
      different clinical diagnoses at 1 year. Future work should determine the extent
      to which these differences can be used to guide clinical care.

PMID- 29034590
TI  - Bimatoprost ophthalmic solution in facial vitiligo.
AB  - BACKGROUND: Vitiligo is one of the commonest pigmentary disorders characterized
      by destruction of melanocytes. AIM: To evaluate the efficacy of topical
      bimatoprost ophthalmic solution in stable facial vitiligo. MATERIAL AND METHODS:
      Eight cases of stable facial vitiligo were treated with bimatoprost 0.03%
      ophthalmic solution once daily for 12 weeks. Photographic records were taken at 2
      weeks follow-up along with dermoscopic (Polarized, 10*) evaluation. RESULTS: Four
      cases had excellent repigmentation, two cases had partial repigmentation and two
      cases had poor response. CONCLUSION: Bimatoprost seems to be promising in
      treating stable vitiligo but large-scale studies are required.

PMID- 29034589
TI  - Involvement of local renin-angiotensin system in immunosuppression of tumor
      microenvironment.
AB  - To improve current cancer immunotherapies, strategies to modulate various
      immunosuppressive cells including myeloid derived suppressor cells (MDSC) which
      were shown to be negative factors in immune-checkpoint blockade therapy, need to
      be developed. In the present study, we evaluated the role of the local renin
      angiotensin system (RAS) in the tumor immune-microenvironment using murine models
      bearing tumor cell lines in which RAS was not involved in their proliferation and
      angiogenetic ability. Giving angiotensin II receptor blockers (ARB) to C57BL/6
      mice bearing murine colon cancer cell line MC38 resulted in significant
      enhancement of tumor antigen gp70 specific T cells. ARB administration did not
      change the numbers of CD11b+ myeloid cells in tumors, but significantly reduced
      their T-cell inhibitory ability along with decreased production of various
      immunosuppressive factors including interleukin (IL)-6, IL-10, vascular
      endothelial growth factor (VEGF), and arginase by CD11b+ cells in tumors. ARB
      also decreased expression of immunosuppressive factors such as chemokine ligand
      12 and nitric oxide synthase 2 in cancer-associated fibroblasts (CAF). Last,
      combination of ARB and anti-programmed death-ligand 1 (PD-L1) antibodies resulted
      in significant augmentation of anti-tumor effects in a CD8+ T cell-dependent way.
      These results showed that RAS is involved in the generation of an
      immunosuppressive tumor microenvironment caused by myeloid cells and fibroblasts,
      other than the previously shown proliferative and angiogenetic properties of
      cancer cells and macrophages, and that ARB can transform the immunosuppressive
      properties of MDSC and CAF and could be used in combination with PD-1/PD-L1
      immune-checkpoint blockade therapy.

PMID- 29034584
TI  - Modern Therapeutic Approaches for Noninfectious Ocular Diseases Involving
      Inflammation.
AB  - Dry eye disease, age-related macular degeneration, and uveitis are ocular
      diseases that significantly affect the quality of life of millions of people each
      year. In these diseases, the action of chemokines, proinflammatory cytokines, and
      immune cells drives a local inflammatory response that results in ocular tissue
      damage. Multiple therapeutic strategies are developed to either address the
      symptoms or abate the underlying cause of these diseases. Herein, the challenges
      to deliver drugs to the relevant location in the eye for each of these diseases
      are reviewed along with current and innovative therapeutic approaches that
      attempt to restore homeostasis within the ocular microenvironment.

PMID- 29034591
TI  - Organ-On-A-Chip Platforms: A Convergence of Advanced Materials, Cells, and
      Microscale Technologies.
AB  - Significant advances in biomaterials, stem cell biology, and microscale
      technologies have enabled the fabrication of biologically relevant tissues and
      organs. Such tissues and organs, referred to as organ-on-a-chip (OOC) platforms,
      have emerged as a powerful tool in tissue analysis and disease modeling for
      biological and pharmacological applications. A variety of biomaterials are used
      in tissue fabrication providing multiple biological, structural, and mechanical
      cues in the regulation of cell behavior and tissue morphogenesis. Cells derived
      from humans enable the fabrication of personalized OOC platforms. Microscale
      technologies are specifically helpful in providing physiological
      microenvironments for tissues and organs. In this review, biomaterials, cells,
      and microscale technologies are described as essential components to construct
      OOC platforms. The latest developments in OOC platforms (e.g., liver, skeletal
      muscle, cardiac, cancer, lung, skin, bone, and brain) are then discussed as
      functional tools in simulating human physiology and metabolism. Future
      perspectives and major challenges in the development of OOC platforms toward
      accelerating clinical studies of drug discovery are finally highlighted.

PMID- 29034592
TI  - Optimizing outcomes after heart transplantation.

PMID- 29034594
TI  - Molecular ReI Cages: Structural and Luminescent Properties.
AB  - Versatile building block [{Re(CO)4 }3 (C3 N3 S3 )] (1 a; C3 N3 S3 =cyanurate
      trianion) reacts with linear dipyridyl ligands [i.e., pyrazine (pz), 4,4'
      bipyridine (bpy), 1,2-bis(4-pyridyl)ethylene (bpe), bis(4-pyridyl)acetylene
      (bpa), and 1,4-bis(pyridyl-4-ylethynyl)benzene (bpb)] and a tripyridyl ligand
      [1,3,5-tris(4-pyridylethynyl)benzene (tpb)] to afford a series of molecular cages
      [{Re(CO)3 }6 (L)3 (C3 N3 S3 )2 ] [L=pz (2), bpy (3), bpe (4), bpa (5), bpb (6)]
      and [{Re(CO)3 }9 (tpb)3 (C3 N3 S3 )3 ] (7) under solvothermal conditions. Various
      structural dimensions and motifs can be systematically tuned and obtained by
      using different dipyridyl and tripyridyl ligands in the reactions. The molecular
      cages of hexanuclear complexes 2-6 containing dipyridyl ligands feature
      interesting trigonal-prismatic structures with different dimensions. Furthermore,
      nonanuclear complex 7 has a novel triangular-star structure, and three benzene
      rings of tpb ligands form a triple-decker arrangement with significant pi???pi
      interactions having distances of 3.490(1) and 3.528(1) A. In addition, molecular
      cages 1-3 and 5-7 exhibit luminescence in the solid state, and their luminescent
      properties were also studied.

PMID- 29034593
TI  - Genetic diversity and comparison of diagnostic tests for characterization of foot
      and-mouth disease virus strains from Pakistan 2008-2012.
AB  - We report the laboratory analysis of 125 clinical samples from suspected cases of
      foot-and-mouth disease (FMD) in cattle and Asian buffalo collected in Pakistan
      between 2008 and 2012. Of these samples, 89 were found to contain viral RNA by
      rRT-PCR, of which 88 were also found to contain infectious FMD virus (FMDV) by
      virus isolation (VI), with strong correlation between these tests (kappa = 0.96).
      Samples that were VI-positive were serotyped by antigen detection ELISA (Ag
      ELISA) and VP1 sequence acquisition and analysis. Sequence data identified FMDV
      serotypes A (n = 13), O (n = 36) and Asia-1 (n = 41), including three samples
      from which both serotypes Asia-1 and O were detected. Serotype A viruses were
      classified within three different Iran-05 sublineages: HER-10, FAR-11 and ESF-10.
      All serotype Asia-1 were within Group VII (Sindh-08 lineage), in a genetic clade
      that differs from viruses isolated prior to 2010. All serotypes O were classified
      as PanAsia-2 within two different sublineages: ANT-10 and BAL-09. Using VP1
      sequencing as the gold standard for serotype determination, the overall
      sensitivity of Ag-ELISA to correctly determine serotype was 74%, and serotype
      specific sensitivity was 8% for serotype A, 88% for Asia-1 and 89% for O.
      Serotype-specific specificity was 100% for serotype A, 93% for Asia-1 and 94% for
      O. Interestingly, 12 of 13 serotype A viruses were not detected by Ag-ELISA. This
      study confirms earlier accounts of regional genetic diversity of FMDV in Pakistan
      and highlights the importance of continued validation of diagnostic tests for
      rapidly evolving pathogens such as FMDV.

PMID- 29034595
TI  - Adamantinoma-like Ewing sarcoma of the parotid gland: Cytopathologic findings and
      differential diagnosis.
AB  - Adamantinoma-like Ewing sarcoma (AES) is a rare variant of Ewing sarcoma family
      of tumors (EFTs), primarily affecting bone and soft tissue. AES has mixed
      features of Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET) and
      adamantinoma with a complex immunoprofile and EWSR1 gene rearrangements. Herein,
      we report a 72-year-old male who presented with left parotid mass, right neck
      mass and thyroid nodules. Fine needle aspiration of the left parotid mass
      displayed nests of monotonous epithelioid cells with basaloid features in a
      background of small round blue cells and lymphocytes. AES can involve head and
      neck region and is characterized by groups of primitive small round blue cells
      admixed with groups of epithelioid cells with amphophilic cytoplasm and focal
      squamous differentiation. The proportion of these components can be variable,
      creating diagnostic challenges, particularly in unusual anatomic sites such as
      the parotid gland. However, when additional material is available, CD99 and/or
      FLI1 immunostains need to be included for diagnostic confirmation.

PMID- 29034596
TI  - Regulation of glucagon-like peptide-1 sensitivity by gut microbiota dysbiosis.
AB  - Gut microbiota dysbiosis reduces expression of GLP-1 receptor (GLP-1R) and
      neuronal nitric oxide synthase (nNOS) in the enteric nervous system and hampers
      GLP-1-induced nitric oxide (NO) production through a pattern recognition receptor
      (PRR)-dependent mechanism, hence preventing activation of the gut-brain-periphery
      axis for control of insulin secretion and gastric emptying.

PMID- 29034597
TI  - Effect of composite type and placement technique on cuspal strain.
AB  - OBJECTIVE: To compare the cuspal strain in Class II restorations made with bulk
      fill and conventional composite resins. MATERIALS AND METHODS: Fifty extracted
      maxillary premolars were mounted into phenolic rings and divided into five groups
      (n = 10). Specimens received standardized MOD preparations. A two-step self-etch
      adhesive was applied and the preparations were restored using a custom matrix as
      follows: Filtek Supreme Ultra in eight 2-mm increments (FSUI); Filtek Supreme
      Ultra in bulk (FSUB); SonicFill in bulk (SF); SureFil SDR flow in bulk, covered
      with a 2-mm occlusal layer of Filtek Supreme Ultra (SDR/FSU); Tetric EvoCeram
      Bulk Fill in bulk (TEBF). Strain gages bonded to the buccal and lingual cusps
      recorded cuspal strain during restorations. End strain values were determined and
      data were subjected to Kruskal-Wallis testing, followed by one-way ANOVA and
      Tukey's post hoc test. RESULTS: Combined strain values and standard deviations
      (in uE) were: FSUI: 723 +/- 102.8, FSUB: 929.2 +/- 571.9, SF: 519.1 +/- 80.2, SDR
      FSU: 497.4 +/- 67.6 and TEBF: 604.5 +/- 127.1. A significant difference was found
      between group FSUI and groups SF, SDR-FSU, and TEBF. Group FSUB showed
      significantly higher mean strain and greater standard deviation than all other
      groups due to cuspal fractures, and was thus excluded from the statistical
      analysis. CONCLUSIONS: The tested bulk-fill composite resins exerted less strain
      onto tooth structure than the incrementally placed conventional composite resin,
      although the magnitude of generated strain was product-dependent. Bulk-filling
      with conventional composite resins is contraindicated. CLINICAL SIGNIFICANCE:
      Bulk-fill composite resins exerted less strain onto adjacent tooth structure than
      a traditional composite, even when that composite is was placed incrementally.
      Bulk-filling with traditional composite resins is unpredictable and
      contraindicated.

PMID- 29034598
TI  - A prospective randomized controlled trial of the two-window technique without
      membrane versus the solo-window technique with membrane over the osteotomy window
      for maxillary sinus augmentation.
AB  - BACKGROUND: Maturation of the grafted volume after lateral sinus elevation is
      crucial for the long-term survival of dental implants. PURPOSE: To compare endo
      sinus histomorphometric bone formation between the solo- and two-window maxillary
      sinus augmentation techniques with or without membrane coverage for the
      rehabilitation of multiple missing posterior teeth. MATERIALS AND METHODS:
      Patients with severely atrophic posterior maxillae were randomized to receive
      lateral sinus floor elevation via the solo-window technique with membrane
      coverage (Control Group) or the two-window technique without coverage (Test
      Group). Six months after surgery, bone core specimens harvested from the lateral
      aspect were histomorphometrically analyzed. RESULTS: Ten patients in each group
      underwent 21 maxillary sinus augmentations. Histomorphometric analysis revealed
      mean newly formed bone values of 26.08 +/- 16.23% and 27.14 +/- 18.11%, mean
      connective tissue values of 59.34 +/- 12.42% and 50.03 +/- 17.13%, and mean
      residual graft material values of 14.6 +/- 14.56% and 22.78 +/- 10.83% in the
      Test and Control Groups, respectively, with no significant differences.
      CONCLUSIONS: The two-window technique obtained comparative maturation of the
      grafted volume even without membrane coverage, and is a viable alternative for
      the rehabilitation of severely atrophic posterior maxillae with multiple missing
      posterior teeth.

PMID- 29034599
TI  - Process and impact of dialectical behaviour therapy: A systematic review of
      perceptions of clients with a diagnosis of borderline personality disorder.
AB  - PURPOSE: To identify, appraise, and synthesize findings from qualitative studies
      of individuals diagnosed with borderline personality disorder who have
      experienced dialectical behaviour therapy, to gain further understanding of their
      perceptions of the process and impact of therapy. METHODS: We conducted a
      comprehensive systematic search of the literature from several online databases,
      and appraised them using an adapted version of the Critical Appraisal Skills
      Programme tool. A meta-ethnographic approach was used to synthesize the data.
      RESULTS: Seven studies met the criteria to be included and their quality
      subsequently appraised. Four main themes were identified through the synthesis
      process: life before DBT; the relationships that support change; developing self
      efficacy; and a shift in perspectives. CONCLUSIONS: The findings of the synthesis
      highlight the importance of a number of key factors in the process of DBT, and
      the impact that the therapy has both on day-to-day life and on individuals'
      identity. PRACTITIONER POINTS: Existing outcome measures may not capture the
      complexity and magnitude of impact of DBT on individuals with BPD. Exploring
      first-hand accounts of individuals undertaking DBT can offer unique insight into
      the processes of therapy.

PMID- 29034600
TI  - No Adverse Programming by Post-Weaning Dietary Fructose of Body Weight,
      Adiposity, Glucose Tolerance, or Metabolic Flexibility.
AB  - SCOPE: Metabolic programming can occur not only in the perinatal period, but also
      post-weaning. This study aims to assess whether fructose, in comparison to
      glucose, in the post-weaning diet programs body weight, adiposity, glucose
      tolerance, metabolic flexibility, and health at adult age. METHODS AND RESULTS:
      Three-week-old male and female C57BL6/JRccHsd mice are given an intervention diet
      with 32 energy percent (en%) glucose or fructose for only 3 weeks. Next, all
      animals are switched to the same 40 en% high fat diet for 9 weeks. Neither body
      weight nor adiposity differs significantly between the animals fed with glucose
      or fructose diets at any point during the study in both sexes. Glucose tolerance
      in adulthood is not affected by the post-weaning diet, nor are activity, energy
      expenditure, and metabolic flexibility, as measured by indirect calorimetry. At
      the end of the study, only in females fasting serum insulin levels and HOMA-IR
      index are lower in post-weaning fructose versus glucose diet (p = 0.02), without
      differences in pancreatic beta-cell mass. CONCLUSIONS: Our present findings
      indicate no adverse programming of body weight, adiposity, glucose tolerance, and
      metabolic flexibility by dietary (solid) fructose in comparison to glucose in the
      post-weaning diet in mice.

PMID- 29034601
TI  - Contact Active Antimicrobial Coatings Prepared by Polymer Blending.
AB  - Herein, contact active antimicrobial films are prepared by simply blending
      cationic amphiphilic block copolymers with commercial polystyrene (PS). The
      copolymers are prepared by combining atom transfer radical polymerization and
      "click chemistry." A variety of copolymers are synthesized, and composed of a PS
      segment and an antimicrobial block bearing flexible side chain with thiazole and
      triazole groups, 4-(1-(2-(4-methylthiazol-5-yl)ethyl)-1H-1,2,3-triazol-4-yl)
      butyl methacrylate (TTBM). The length of the TTBM block is varied as well as the
      alkylating agent. Different films are prepared from N,N-dimethylformamide
      solution, containing variable PS-b-PTTBM/PS ratio: from 0 to 100 wt%. Remarkably,
      the blend films, especially those with 30 and 50 wt% of copolymers, exhibit
      excellent antimicrobial activities against Gram-positive, Gram-negative bacteria
      and fungi, even higher than films prepared exclusively from the cationic
      copolymers. Blends composed of 50 wt% of the copolymers present a more than
      99.999% killing efficiency against the studied microorganisms. The better
      activity found in blends can be due to the higher roughness, which increases the
      surface area and consequently the contact with the microorganisms. These results
      demonstrate that the use of blends implies a reduction of the content of
      antimicrobial agent and also enhances the antimicrobial activity, providing new
      insights for the better designing of antimicrobial coatings.

PMID- 29034602
TI  - Gender and arch effects on the use of non-opioid analgesics for post endodontic
      pain reduction.
AB  - This study aimed to evaluate the secondary outcomes of gender and arch and their
      impact on pain reduction following initial endodontic therapy. 185 medications,
      including placebo were prepared, and 170 participants completed the trial. Group
      1, received a single dose of Paracetamol alone (G-1), Group 2 received combined
      Ibuprofen/Paracetamol (G-2). Group 3 received combined Mefenamic acid/Paracetamol
      (G-3), group 4 received combined Diclofenac K/Paracetamol (G-4) and Group 5
      received a placebo (G-5). There were no statistically significant differences in
      pain reduction between males and females whilst there were statistically
      significant differences between them and the placebo group. All combinations of
      Paracetamol performed better in pain reduction than the placebo among females,
      while there were no statistically significant differences among males. In
      conclusion, there were no differences in pain reduction between males and
      females, and arch for the tested analgesics taken immediately following initial
      endodontic therapy in teeth with irreversible pulpitis.

PMID- 29034605
TI  - Useful aspects of diagnosis of imprint cytology in intraoperative consultation of
      ovarian tumors: comparison between imprint cytology and frozen sections.
AB  - BACKGROUND: In the intraoperative consultation of ovarian tumors, the
      histological diagnosis of frozen sections (FS) of large tumors is frequently
      difficult because of the limited number of tumor samples. The application of
      imprint cytology (IC), in which samples are obtained from wide areas of the
      tumors, is useful for intraoperative consultation. However, the useful aspects of
      IC have not been clearly defined. The present study is a detailed comparison of
      IC and FS that clearly defines the useful aspects of IC. METHODS: Fifty-five
      cases of ovarian tumors that were examined using both IC and FS were evaluated.
      The histological diagnoses consisted of benign (16), borderline (6), and
      malignancy (33). All of the malignant tumors consisted of various types of
      carcinoma. RESULTS: Benignity and malignancy were accurately diagnosed by both IC
      and FS. In the borderline group, the diagnostic accuracy of IC was very low (1/6:
      16.6%) compared with FS (4/6: 66.6%). The diagnostic accuracy including benign,
      borderline, and malignant groups was 90.9% (50/55) for IC and 96.3% (53/55) for
      FS. Concerning the diagnosis of the types of carcinoma, the overall diagnostic
      accuracy of IC (25/31: 80.6%) was greater than that of FS (21/31: 67.7%),
      especially for the diagnosis of clear cell carcinoma (IC, 100%; FS, 80%) and
      mixed carcinoma (IC, 66.6%; FS, 16.6%). CONCLUSION: The useful aspects of IC in
      the intraoperative consultation are the diagnosis of benignity or malignancy and
      the accuracy of diagnosing clear cell carcinoma and mixed carcinoma.

PMID- 29034606
TI  - Do Mid-Crown Enamel Formation Front Angles Reflect Factors Linked to the Pace of
      Primate Growth and Development?
AB  - Enamel formation front (EFF) angles represent the leading edge of enamel matrix
      secretion at particular points in time. These angles are influenced by rates of
      enamel extension (the rates at which tooth crowns grow in height), rates of
      enamel matrix secretion and the angles that prisms make with the enamel-dentine
      junction. Previous research suggests, but has not yet established, that these
      angles reflect aspects of primate biology related to their pace of growth and
      development, most notably brain and body size. The present study tested this
      possibility on histological sections using phylogenetically-controlled and
      Bonferroni-corrected analyses spanning a broad taxonomic range. Ten species were
      represented in the analysis of anterior teeth; 17 in the analysis of posterior
      (postcanine) teeth (with varying sample sizes). Also, tested was the relationship
      of EFF angles to striae of Retzius periodicity (long period growth rhythms in
      enamel) and degree of folivory, as both factors are related to primate
      developmental rates. Finally, several analyses were conducted to investigate
      whether tooth size (operationalized as EDJ length) might mediate these
      relationships. Central results are as follows: (1) Relationships between EFF
      angles and brain weight (anterior teeth) and between EFF angles and body mass
      (anterior and posterior teeth) are statistically significant and (2) Mid-crown
      EFF angles are not statistically significantly related to EDJ lengths. These
      results suggest that tooth size does not mediate relationships between EFF angles
      and brain weight/body mass and are discussed with respect to underlying enamel
      growth variables (especially rates of enamel extension and secretion). Anat Rec,
      2017. (c) 2017 Wiley Periodicals, Inc. Anat Rec, 301:125-139, 2018. (c) 2017
      Wiley Periodicals, Inc.

PMID- 29034607
TI  - Complete loss of insulin secretion capacity in type 1A diabetes patients during
      long-term follow up.
AB  - AIM/INTRODUCTION: Patients with type 1 diabetes are classified into three
      subtypes in Japan: acute onset, fulminant and slowly progressive. Acute-onset
      type 1 diabetes would be equivalent to type 1A diabetes, the typical type 1
      diabetes in Western countries. The insulin secretion capacity in Japanese
      patients with long-standing type 1A diabetes is unclear. The aim of the present
      study was to clarify the course of endogenous insulin secretion during long-term
      follow up and the factors associated with residual insulin secretion in patients
      with acute-onset type 1 diabetes (autoimmune). MATERIALS AND METHODS: We
      retrospectively investigated endogenous insulin secretion capacity in 71 patients
      who fulfilled the diagnostic criteria for acute-onset type 1 diabetes
      (autoimmune) in Japan. To assess the residual insulin secretion capacity, we
      evaluated randomly measured C-peptide levels and the results of glucagon
      stimulation test in 71 patients. RESULTS: In the first year of disease, the child
      and adolescent-onset patients had significantly more in residual insulin
      secretion than the adult-onset patients (34 patients in total). C-peptide levels
      declined more rapidly in patients whose age of onset was <=18 years than in
      patients whose age of onset was >=19 years. Endogenous insulin secretion capacity
      stimulated by glucagon was completely lost in almost all patients at >15 years
      after onset (61 patients in total). CONCLUSIONS: Most patients with acute-onset
      type 1 diabetes (autoimmune) completely lose their endogenous insulin secretion
      capacity during the disease duration in Japan. Age of onset might affect the
      course of insulin secretion.

PMID- 29034609
TI  - Mental health in rural Australia.

PMID- 29034610
TI  - Private health insurance - a good deal in rural and remote Australia?

PMID- 29034611
TI  - Epidemiology and spatio-temporal analysis of West Nile virus in horses in Spain
      between 2010 and 2016.
AB  - During the last decade, West Nile virus (WNV) outbreaks have increased sharply in
      both horses and human in Europe. The aims of this study were to evaluate
      characteristics and spatio-temporal distribution of WNV outbreaks in horses in
      Spain between 2010 and 2016 in order to identify the environmental variables most
      associated with WNV occurrence and to generate high-resolution WNV suitability
      maps to inform risk-based surveillance strategies in this country. Between August
      2010 and November 2016, a total of 403 WNV suspected cases were investigated, of
      which, 177 (43.9%) were laboratory confirmed. Mean values of morbidity, mortality
      and case fatality rates were 7.5%, 1.6% and 21.2%, respectively. The most common
      clinical symptoms were as follows: tiredness/apathy, recumbency, muscular tremor,
      ataxia, incoordination and hyperaesthesia. The outbreaks confirmed during the
      last 7 years, with detection of WNV RNA lineage 1 in 2010, 2012, 2013, 2015 and
      2016, suggest an endemic circulation of the virus in Spain. The spatio-temporal
      distribution of WNV outbreaks in Spain was not homogeneous, as most of them
      (92.7%) were concentrated in western part of Andalusia (southern Spain) and
      significant clusters were detected in this region in two non-consecutive years.
      These findings were supported by the results of the space-time scan statistics
      permutation model. A presence-only MaxEnt ecological niche model was used to
      generate a suitability map for WNV occurrence in Andalusia. The most important
      predictors selected by the Ecological Niche Modeling were as follows: mean annual
      temperature (49.5% contribution), presence of Culex pipiens (19.5% contribution),
      mean annual precipitation (16.1% contribution) and distance to Ramsar wetlands
      (14.9% contribution). Our results constitute an important step for understanding
      WNV emergence and spread in Spain and will provide valuable information for the
      development of more cost-effective surveillance and control programmes and
      improve the protection of horse and human populations in WNV-endemic areas.

PMID- 29034612
TI  - Variability index of tacrolimus serum levels in pediatric liver transplant
      recipients younger than 12 years: Non-adherence or risk of non-adherence?
AB  - MLVI has been used to assess adherence. To determine the MLVI in children <12
      years of age at transplantation and to identify demographic correlates and
      consequences for the graft. This is a retrospective study of 50 outpatients (4.0
      +/- 3.5 years), at least 13-month post-liver transplantation. The outcomes
      evaluated were MLVI, ALT > 60 IU/L, ACR, death, and graft loss. We analyzed
      demographic and socioeconomic characteristics, indication for transplantation,
      and type of donor. Student's t test and the chi-square test were used.
      Statistical significance was set at P <= .05. Seventy-two percent were infants or
      preschoolers, 62% biliary atresia. Seventy-four percent of the mothers had middle
      school education, and 54% of the families had an income <=3632.4 US$/y. Twenty
      two (44%) patients had a MLVI >= 2 SD; this was more prevalent in families with
      higher incomes (P = .045). ALT levels > 60 IU/L were more common in MLVI >= 2 SD
      group (P = .035). ACR episodes were similar between groups (P = 1.000). No
      patient died or lost the graft. MLVI >= 2 SD may be an indicator of the risk of
      medication non-adherence.

PMID- 29034613
TI  - Massive ascites and the heterozygous alpha 1 antitrypsin (alpha1 AT) living
      related donor liver in the homozygous child.
AB  - The following is a short report on the use of a heterozygous (PiMZ) alpha 1
      antitrypsin (alpha1AT) living related donor liver in a homozygous (PiZ) child
      that was complicated by massive ascites early after transplant. This clinical
      report is then followed by a brief summary of present knowledge on the alpha1 AT
      protein and management of massive ascites in the pediatric liver transplant
      recipient.

PMID- 29034608
TI  - Nanoparticle-Based Therapeutics for Brain Injury.
AB  - Brain injuries affect a large patient population with major physical and
      emotional suffering for patients and their relatives; at a significant cost to
      the society. Effective diagnostic and therapeutic options available for brain
      injuries are limited by the complex brain injury pathology involving blood-brain
      barrier (BBB). Brain injuries, including ischemic stroke and brain trauma,
      initiate BBB opening for a short period of time, which is followed by a second
      reopening for an extended time. The leaky BBB and/or the alterations in the
      receptor expression on BBB may provide opportunities for therapeutic delivery via
      nanoparticles (NPs). The approaches for therapeutic interventions via NP delivery
      are aimed at salvaging the pericontusional/penumbra area for possible
      neuroprotection and neurovascular unit preservation. The focus of this progress
      report is to provide a survey of NP strategies employed in cerebral ischemia and
      brain trauma and finally provide insights for improved NP-based
      diagnostic/treatment approaches.

PMID- 29034614
TI  - Selenium supplementation during in vitro maturation enhances meiosis and
      developmental capacity of yak oocytes.
AB  - The objectives of the present study were to investigate the effects of selenium
      (Se) supplementation during in vitro maturation (IVM) on the developmental
      capacity of yak (Bos grunniens) oocytes. Nuclear maturation, DNA integrity,
      glutathione peroxidase (GSH-Px) activity, subsequent embryonic development, and
      gene expression after in vitro fertilization (IVF) were evaluated. The Se
      concentrations in yak plasma and follicular fluid were 0.142 and 0.069 MUg/mL,
      respectively. The DNA damage in cumulus cells decreased significantly with 2 and
      4 MUg/mL supplementation of sodium selenite to IVM medium (P < 0.05). Total GSH
      Px activity in oocytes increased in all Se supplementation groups, and the 2 and
      4 MUg/mL groups were significantly higher than the control group (0 MUg/mL).
      However, the cleavage rate was not significantly different after Se
      supplementation (P > 0.05). The IVF blastocyst formation rates of 0, 1 and 4
      MUg/mL sodium selenite groups were 47.7%, 51.2% and 58.9%, respectively. The 2
      MUg/mL sodium selenite group had the highest blastocyst formation rate (60.5%).
      Gene expression analysis revealed that the quantity of transcripts associated
      with selenoprotein and protein synthesis were high in the 2 and 4 MUg/mL groups.
      In conclusion, both GSH-Px activity of oocytes and DNA integrity of cumulus cells
      significantly increased with supplemental Se during oocyte IVM. Considering that
      embryonic development is responsive to Se supplementation, we inferred that
      appropriate Se concentrations during IVM were beneficial for yak oocyte
      maturation and subsequent development.

PMID- 29034615
TI  - Effects of an exercise model based on functional circuits in an older population
      with different levels of social participation.
AB  - AIM: To investigate whether being part of a community organization interfered
      with older adults' overall functionality. The magnitude of responses to a
      community exercise program based on functional circuits in socially active and
      socially non-active older adults was also investigated. METHODS: A total of 200
      older adults aged >=60 years from Requinoa, Chile, participated in the study.
      Participants were separated into two groups according to the level of social
      participation: socially active (SA) and socially non-active (SNA). During an
      evaluation, data regarding the presence of comorbidities (Charlson Comorbidity
      Index), disability level (Modified Health Assessment Questionnaire), dynamic
      balance (Timed Up and Go test), muscle force (handgrip dynamometry) and
      sociodemographic conditions were collected. Participants followed an exercise
      program consisting of a functional exercise circuit including balance, resistance
      and aerobic exercises, twice a week, for 12 weeks. RESULTS: Both the Charlson
      Comorbidity Index and disability were higher in SNA compared with SA participants
      on inclusion. Both groups improved disability (Delta-0.25 patients [-0.5 - 
      0.0625 patients] for SNA and (Delta-0.125 patients [-0.5-0 patients] for SA) and
      balance (Delta-2 s [-3-0 s] for SNA and (Delta-1 s [-3-0 s] for SA) after
      training (P < 0.05 for all). Changes from baseline were statistically higher in
      the SNA group. Handgrip force improved only in participants in the SNA group
      (Delta1.7 kg [0.6-2.8 kg], P = 0.0001). No differences, however, were observed
      between the magnitude of improvements of handgrip between groups. CONCLUSIONS:
      Although socially non-active older adults had more comorbidity and disability
      than their socially active counterparts, they showed a higher response to a
      community exercise program. Geriatr Gerontol Int 2018; 18: 216-223.

PMID- 29034616
TI  - Molecular survey and genetic characterization of Anaplasma centrale, A. marginale
      and A. bovis in cattle from Algeria.
AB  - Bovine anaplasmosis could be caused by several Anaplasma species. The causative
      agents are transmitted by ticks and haematophagous arthropods with a high impact
      on both human and animal health. This study was conducted to estimate the
      infection rate and to characterize Anaplasma spp. in cattle from Algeria. A
      molecular survey was performed in Setif district (Northeast Algeria) where a
      total number of 180 cattle blood samples were collected and tested for the
      presence of Anaplasma spp. by PCR. Positive samples were genetically
      characterized based on the 16S rRNA and msp4 genes. PCRs revealed that the
      infection rates of Anaplasma spp., Anaplasma centrale, Anaplasma marginale and
      Anaplasma bovis were 42.2%; 39.4%; 11.1% and 4.4%, respectively. All tested
      animals were negative for A. phagocytophilum. Co-infection occurred in 10%
      (18/180) of the tested animals, and the most common co-infection pattern was an
      association between A. centrale and A. marginale (5.5%). Five cattle (2.7%) were
      co-infected by the three Anaplasma species. Holstein animals (58.1%) were more
      infected by A. centrale than the other breeds (p = .01). The molecular prevalence
      of A. centrale was significantly higher in males (54.2%) than in females (34.1%)
      (p = .001). A. marginale msp4 genetic analysis indicated a high sequence
      diversity of Algerian strains, suggesting the importation of live cattle from
      different origins. Phylogenetic analysis of the 16S rRNA gene of A. bovis and A.
      centrale revealed a low degree of genetic diversity. Our study suggests that
      different species of Anaplasma are simultaneously present in the Algerian cattle.
      To the best of our knowledge, this is the first molecular study and genetic
      characterization of Anaplasma spp. in Algerian cattle.

PMID- 29034618
TI  - Altered Electroencephalography Spectral Profiles in Rats with Different Patterns
      of Experimental Brain Dysplasia.
AB  - BACKGROUND: Malformations of cortical development, such as focal cortical
      dysplasia, are commonly associated with intractable epilepsy. Multiple animal
      models were created in attempts to recapitulate features of human malformations
      of cortical development. These manipulations give rise to various focal or
      diffuse anatomical abnormalities, accompanied by altered susceptibility to
      epileptic seizures. Both in humans and in models of dysplasia, the question of
      timing of the initiating insult is important. METHODS: Here, we used a rat model
      of cerebral dysplasia elicited by prenatal irradiation at gestational days (E)
      13, 15, 17, or 19. Previous results suggest these animals are characterized by
      different patterns of dysplasia as well as different reactivity to seizurogenic
      stimuli in several seizure models. Rats were implanted with telemetric
      electroencephalography (EEG) transmitters. We compared EEG data from freely
      moving animals with anatomical observations obtained with MRI, as well as Western
      blotting and immunohistochemistry. RESULTS: We performed spectral analyses of EEG
      signal, revealing differential regulation of specific bands (including delta,
      theta, alpha-beta, gamma) in animals with different patterns of dysplasia.
      Relative contribution of low-frequency activity in delta band is the lowest in
      E15 and the highest in E19. Conversely, higher frequency bands, corresponding to
      alpha/beta and gamma components, are reduced in E15 versus E19. This is
      accompanied by altered expression of glial markers in the E19 group. CONCLUSION:
      To our knowledge, this constitutes the first quantitative description of power
      spectral properties in this experimental model, providing insight into mechanisms
      underlying the anatomical and electrophysiological abnormalities associated with
      brain dysplasia of different types. Birth Defects Research, 110:303-316, 2018.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 29034617
TI  - Isolation and characterization of avian influenza viruses from raw poultry
      products illegally imported to Japan by international flight passengers.
AB  - The transportation of poultry and related products for international trade
      contributes to transboundary pathogen spread and disease outbreaks worldwide. To
      prevent pathogen incursion through poultry products, many countries have
      regulations about animal health and poultry product quarantine. However, in
      Japan, animal products have been illegally introduced into the country in baggage
      and confiscated at the airport. Lately, the number of illegally imported poultry
      and the incursion risk of transboundary pathogens through poultry products have
      been increasing. In this study, we isolated avian influenza viruses (AIVs) from
      raw poultry products illegally imported to Japan by international passengers.
      Highly (H5N1 and H5N6) and low (H9N2 and H1N2) pathogenic AIVs were isolated from
      raw chicken and duck products carried by flight passengers. H5 and H9 isolates
      were phylogenetically closely related to viruses isolated from poultry in China,
      and haemagglutinin genes of H5N1 and H5N6 isolates belonged to clades 2.3.2.1c
      and 2.3.4.4, respectively. Experimental infections of H5 and H9 isolates in
      chickens and ducks demonstrated pathogenicity and tissue tropism to skeletal
      muscles. To prevent virus incursion by poultry products, it is important to
      encourage the phased cleaning based on the disease control and eradication and
      promote the reduction in contamination risk in animal products.

PMID- 29034619
TI  - [Induction and regulation of cellulase expression in filamentous fungi: a
      review].
AB  - Production of bioenergy and bio-based chemicals by using fermentable sugars
      released from low-cost renewable lignocellulosic biomass has received great
      attention. Efficient cellulolytic enzymes are crucial for lignocellulose
      bioconversion, but high cellulase production cost is limiting the bioconversion
      efficiency of cellulosic biomass and industrial applications of lignocellulose
      biorefinery. Studies on induction and regulation of cellulase in filamentous
      fungi will help to further develop superior fungal strains for efficient
      cellulase production and reduce cellulase production cost. With the advances in
      high-throughput sequencing and gene manipulation technology using fungal strains,
      an in-depth understanding of cellulase induction and regulation mechanisms of
      enzyme expression has been achieved. We reviewed recent progresses in the
      induction and regulation of cellulase expression in several model filamentous
      fungi, emphasizing sugar transporters, transcription factors and chromatin
      remodeling. Future prospects in application of artificial zinc finger proteins
      for cellulase induction and regulation in filamentous fungi were discussed.

PMID- 29034620
TI  - [Progress in chemicals production by microbial consortia].
AB  - Using cheap biomass resources is a hotspot of research on industrial
      biotechnology. It is difficult for traditional fermentations with single strain
      to treat so complex components and more impurities, which becomes the key problem
      in industrialization. In this review, some existing industrial bioprocesses
      involving microbial consortia were described. Comparison of 1,3-propanediol
      production by microbial consortia and pure cultures were then introduced and the
      relationship between cells in microbial consortia were summarized. Finally, the
      perspective was also addressed to design and apply microbial consortia in the
      future.

PMID- 29034621
TI  - [Circular RNAs and their roles in tumorigenesis].
AB  - Recently, with the development of RNA research techniques, a wide variety of
      circular RNAs (circRNAs) have been discovered and some of them are confirmed to
      have crucial biological functions. CircRNAs arise from exons (i.e. exonic
      circRNAs) or introns (i.e. intronic circRNAs). Acting as microRNA sponges or
      combining with proteins, circRNAs participate in the regulation of gene
      expression and influence the activity of some proteins. In addition, some
      circRNAs even encode proteins. More importantly, several circRNAs play a key role
      in the occurrence and progression of some tumors, including stomach, liver,
      colon, breast, cervical, and ovarian cancers. Therefore, circRNAs may be a novel
      type of diagnostic marker and therapeutic target of cancers.

PMID- 29034622
TI  - [Establishment of chemiluminescent enzyme immunoassay for detecting antibodies
      against foot-and-mouth disease virus serotype O in swine].
AB  - Recombinant structural protein VP1 of foot-and-mouth disease virus serotype O was
      expressed in Escherichia coli and then purified using Nickel affinity
      chromatography. A chemiluminescent enzyme immunoassay (CLEIA) method was
      established using the purified recombinant protein as coating antigen to detect
      antibody of foot-and-mouth disease virus serotype O in swine. The specificity of
      VP1-CLEIA method is 100%. The coefficients of variation in the plate and between
      plates are 1.10%-6.70% and 0.66%-4.80%, respectively. Comparing with the
      commercial indirect ELISA kit or liquid phase block ELISA kit, the calculated
      coincidence rate is 93.50% or 94.00%. The high specificity and stability
      suggested this detection method can be used to monitor the antibody level of foot
      and-mouth disease virus serotype O in swine.

PMID- 29034623
TI  - [Characterization and application of a monoclonal antibody against light chain of
      goose immunoglobulin].
AB  - Immunoglobulin (Ig) is considered a part of the innate immune system and
      cooperates with the complementary system as the first line of defense. In this
      study, a monoclonal antibody (MAb) direct against the light chain of goose Ig
      (GoIgCL) was generated, characterized and identified in various immunoassays to
      detect goose Ig. An immunoaffinity chromatography column prepared with this MAb
      was used to separate the goose Ig from sera. After being conjugated with
      horseradish peroxidase (HRP), this MAb was used as the secondary antibody to
      evaluate the goose-specific antibody. In addition, this MAb distinguished and
      localized the SIg+ lymphocytes from peripheral blood lymphocytes. MAb against
      GoIgCL may be good candidate to detect or purify goose Ig under various
      conditions and as a powerful tool for humoral immunity research on goose.

PMID- 29034624
TI  - [Effects of overexpression of carboxylation pathway genes and inactivation of
      malic enzymes on malic acid production in Escherichia coli].
AB  - Malic acid is a dicarboxylic acid that is widely used in food, pharmaceutical and
      chemical industries. We studied the effects of overexpression of carboxylation
      pathway genes and inactivation of malic enzymes on the aerobic production of
      malic acid. Over expression of phosphoenolpyruvate (PEP) carboxylase (ppc)
      generated strain E21, which increased malic acid production from 0.57 g/L to 3.83
      g/L. Then pyc gene from Coryenbacterium glutamicus and pck gene from
      Actinobacillus succinogenes were overexpressed in E21 separately. The resulting
      strains E21 (pTrcpyc) and E21 (pTrc-A-pck) produced 6.04 and 5.01 g/L malate with
      a yield of 0.79 and 0.65 mol/mol glucose, respectively. Deleting two malic
      enzymes (encoded by maeA and maeB) also led to an increase of 36% in malic acid
      production with a production of 5.21 g/L. However, the combination of malic
      enzymes deletion and pyc overexpression could not further increase the yield of
      malic acid. After optimization of fermentation conditions, strain E21 (pTrcpyc)
      produced 12.45 g/L malic acid with a yield of 0.84 mol/mol which is 63.2% of the
      theoretical yield.

PMID- 29034625
TI  - [Pilot-scale purification of lipopeptide from marine-derived Bacillus marinus].
AB  - This research was aimed at establishing the pilot-scale purification technology
      of lipopeptide from marine-derived Bacillus marinus. We studied lipopeptide
      surfactivity interferences on scale-up unit technologies including acid
      precipitation, methanol extraction, solvent precipitation, salting out,
      extraction, silica gel column chromatography and HZ806 macroporous absorption
      resin column chromatography. Then, the unit technologies were combined in a
      certain order, to remove the impurities gradually, and to gain purified
      lipopeptide finally, with high recovery rate throughout the whole process. The
      novel pilot-scale purification technology could effectively isolate and purify
      lipopeptide with 87.51% to 100% purity in hectograms from 1 ton of Bacillus
      marinus B-9987 fermentation broth with more than 81.73% recovery rate. The first
      practical hectogram production of highly purified lipopeptide derived from
      Bacillus marinus was achieved. With this new purification method, using complex
      media became possible in fermentation process to reduce the fermentation cost and
      scale-up the purification for lipopeptide production. For practicability and
      economy, foaming problem resulting from massive water evaporation was avoided in
      this technology.

PMID- 29034626
TI  - [Sequence analysis and expression patterns of histone H2A variants in
      Phytophthora infestans].
AB  - In eukaryotic cells, DNA is packaged inside the nucleus together with histones to
      form nucleosomes. Each histone molecule contains two of each core histone
      subunits H2A, H2B, H3 and H4. Among core histones, the H2A family is of great
      interest due to the high diversity of specialized variants. These variants have
      shown important role in critical cellular processes. Epigenetic mechanism in
      oomycetes is barely known. Phytophthora infestans is a severe pathogen and a
      model species in oomycetes. In this study, we studied the sequence and expression
      pattern of H2A variants of P. infestans through genome search, sequences
      alignment, phylogenetic analysis and realtime qPCR detection. P. infestans
      contains conserved genes encoding histone variants H2A.X.1, H2A.X.2 and H2A.Z,
      and these genes have specific expression patterns during development and
      infection stages. Our datasets provide useful inputs to help explore the
      epigenetic mechanisms of oomycetes.

PMID- 29034627
TI  - [Detection of transgenic components in animal feeds on Shanxi markets].
AB  - To assess the presence of genetically modified (GM) maize and soybean in a range
      of commercialized feed in Shanxi province of China in 2015, improved
      hexadecyltrimethy ammonium bromide (CTAB) method was used to extract DNA. The
      screening of packed feeds was carried out by qualitative PCR. Then positive feeds
      were unpacked and detected by the CaMV 35S promoter, NOS terminator, zSSIIb,
      Lectin and CryIA (b) genes. The identified maize and soybean events were
      confirmed by event-specific MON810 and GTS40-3-2. Results showed that 83.3% of
      the feeds was tested positive for GMOs, in which positive rates of maize,
      soybean, pig and layer feeds were 6.67%, 100%, 93.3% and 73.3%, respectively. The
      results of real-time PCR were consistent with qualitative PCR. These results
      indicated that commercialized GM feed had a wide positive product scope in Shanxi
      province of China. Further studies are necessary to study effects of feeding
      livestock and poultry with feed containing GM ingredients on animals and their
      products.

PMID- 29034629
TI  - [Comparison of cellular localization of NS1 from different subtypes of influenza
      A virus].
AB  - The non-structural (NS1) protein is a multifunctional molecular protein encoded
      by influenza A virus genome. NS1 plays an important role in inhibition of host
      immune responses. In order to assess the cellular localization of NS1 in
      different influenza A virus subtypes, we performed the immunofluorescence assay
      to observe the cellular location of NS1 after infection with influenza A virus
      WSN (H1N1), PR8 (H1N1), CA04 (H1N1), SD (H9N2) and AH01 (H7N9) in A549 cells and
      MDCK cells respectively. According to the results, NS1-WSN and NS1-PR8
      accumulated mainly in cytoplasm at 24 h post infection, while the NS1-CA04 and
      NS1-SD appeared major in the nucleus. We also observed localization of NS1 by
      transfected 293T cells with plasmids which encoding the full-length NS1 from WSN,
      SD and AH01. The key sites which might determine the different cellular
      localization of NS1 were chosen by sequence alignment, and seven residues which
      were different between WSN, PR8 and CA04, SD and AH01 were finally focused.
      However, we found that single mutation of these residues could not alter the
      localization of NS1. The data indicated that the difference of location might not
      be caused by substitution of a single site, which contributes to our
      understanding of the diverse regulation of host factors during different subtypes
      of influenza virus infection.

PMID- 29034628
TI  - [Screening of full human anthrax lethal factor neutralizing antibody in
      transgenic mice].
AB  - Anthrax is a highly lethal infectious disease caused by the spore-forming
      bacterium Bacillus anthracis. The major virulence factor of B. anthracis consists
      of protective antigen (PA), lethal factor (LF) and edema factor (EF). PA binds
      with LF to form lethal toxin (LT), and PA binds with EF to form edema toxin (ET).
      Antibiotics is hard to work in advanced anthrax infections, because injuries and
      deaths of the infected are mainly caused by lethal toxin (LT). Thus, the
      therapeutic neutralizing antibody is the most effective treatment of anthrax.
      Currently most of the anthrax toxin antibodies are monoclonal antibodies (MAbs)
      for PA and US FDA has approved ABTHRAX humanized PA monoclonal antibody for the
      treatment of inhalational anthrax. Once B. anthracis was artificially
      reconstructed or PA had mutations within recognized neutralization epitopes, anti
      PA MAbs would no longer be effective. Therefore, anti-LF MAbs is an important
      supplement for anthrax treatment. Most of the anti-LF antibodies are murine or
      chimeric antibodies. By contrast, fully human MAbs can avoid the high
      immunogenicity of murine antibodies. First, we used LF to immunize the transgenic
      mice and used fluorescent cell sorting to get antigen-specific memory B cells
      from transgenic mice spleen lymphocytes. By single cell PCR method, we quickly
      found two strains of anti-LF MAbs with binding activity, 1D7 and 2B9. Transiently
      transfected Expi 293F cells to obtain MAbs protein after purification. Both 1D7
      and 2B9 efficiently neutralized LT in vitro, and had good synergistic effect when
      mixed with anti-PA MAbs. In summary, combining the advantages of transgenic mice,
      fluorescent cell sorting and single-cell PCR methods, this study shows new ideas
      and methods for the rapid screening of fully human monoclonal antibodies.

PMID- 29034631
TI  - [Filamentous fungal sesterterpenoids and their synthases].
AB  - Although the number of sesterterpenoids is fewer than other terpenoids reported,
      they have presented a wide range of biological activities and medicinal value.
      Reported filamentous fungal sesterterpene synthases are special on bifunctional
      two catalytically independent domains: prenyltransferase and terpene cyclase, but
      less specific on substrates selection and diverse ways of cyclization. This
      article reviews the research advances in filamentous fungal sesterterpenoids and
      their synthases, especially describes filamentous fungal sesterterpenoids and the
      structure and function characteristics of sesterterpene synthase.

PMID- 29034630
TI  - [Transcriptome analysis and gene function annotation of Bambusa emeiensis shoots
      based on high-throughput sequencing technology].
AB  - Bambusa emeiensis is one of the preponderant species of sympodial bamboos in
      Sichuan province of China, and has excellent fiber length and quality as raw
      materials for papermaking, textile and other industries. In this study, with the
      application of Illumina HiSeqTM 2000 platform, we analyzed transcriptome in B.
      emeiensis with different heights of 10, 50, 100 and 150 cm. A total of 69.28 M
      reads were obtained, and a sum up of 111 137 bands of Unigenes were acquired
      following de novo stitching, assembly and clustering, among which there were 63
      094 bands that had been integrated in the COG, GO, KEGG, Swiss-Prot and Nr
      databases using annotated methods. These Unigenes not only had general functions,
      such as transcription and signal transduction, but were also involved in sucrose
      transport and metabolism, secondary metabolites and cell wall biosynthesis. There
      was significant difference regarding the expression of cellulose synthase gene in
      B. emeiensis at different heights, relevant genes were found that might be
      responsible for the regulation of the growth and development of B. emeiensis as
      well as the biosynthesis of cellulose and lignin. Our findings could provide some
      elementary theories for breed improvement of B. emeiensis.

PMID- 29034632
TI  - [Research progress and stress-induced variation of DNA methylation in plants].
AB  - Chemical modification of DNA bases in recent years has been one of the hot areas
      of life science research. DNA methylation is a common epigenetic phenomenon and
      can change the genetic performance without changing the DNA sequence. Various
      stress factors can induce the variation of DNA methylation in plants, but the
      response mechanism is still unknown. In this paper, the progress of DNA
      methylation in plants was reviewed. In combination with the researchconclusions
      of our own research group, the DNA methylation variation induced by 7Li ion beam
      and gamma ray was reported to provide a basis for DNA methylation, which may be
      involved in the phenotypic plasticity of plants.

PMID- 29034633
TI  - [Comparison of effects of staphylococcal nuclease A fused with different
      exogenous DNA fragments].
AB  - Staphylococcal nuclease A (SNA) may be used to produce bacterial ghosts for
      further inactivation of host bacteria and elimination of residual genetic
      materials. It is still controversial if SNA without signal peptide can be
      secreted to extracellular matrix and if fusion with other peptide is required for
      its function in the cytoplasm of host bacteria. To clarify this dispute, a series
      of temperature-inducible plasmids carrying SNA alone or SNA fused with partial
      sequences of lambda phage cro gene (cSNA) or Mycobacterium tuberculosis urease
      gene (uSNA) were constructed and evaluated in Escherichia coli. Results show that
      the percentages of inactivated E. coli by SNA, cSNA and uSNA after 4 h of
      induction were 99.9%, 99.8% and 74.2%, respectively. Moreover, SNA and cSNA in
      the cytoplasm of host bacteria were initially detectable after 30 min of
      induction, whereas uSNA was after 1 h. In comparison, SNA and cSNA in culture
      supernatant were initially detectable 1 h later, whereas uSNA was 2 h later. The
      nuclease activity in the cytoplasm or supernatant was ranked as follows: SNA >
      cSNA > uSNA, and the activity in the supernatant was significantly lower than
      that in the cytoplasm. Furthermore, host genomic DNA was degraded by SNA or cSNA
      after 2 h of induction but not by uSNA even throughout the whole experiment. In
      conclusion, this study indicates that SNA, cSNA and uSNA expressed in host
      bacteria all have nuclease activity, the enzymes can be released to culture
      media, and fusion with exogenous peptide negatively reduces the nuclease activity
      of SNA.

PMID- 29034634
TI  - [Construction and characterization of type III secretion system of attenuated
      Salmonella typhimurium].
AB  - In order to develop a recombinant attenuated Salmonella typhimurium as oral live
      vaccine vector, we constructed recombinant plasmid pYA-sopENt100 by replacing the
      trc promoter with the sopE promoter and secretion signal sequence sopENt100 of
      Salmonella typhimurium on the basis of plasmid pYA3493. Then, the complementary
      plasmid pYA-sopENt100 was transformed into DeltacrpDeltaasdSL1344 by
      electroporation to generate attenuated Salmonella typhimurium type III secretion
      system DeltacrpDeltaasdSL1344 (pYA-sopENt100). We further characterized
      DeltacrpDeltaasdSL1344 (pYA-sopENt100). We also constructed a recombinant strain
      DeltacrpDeltaasdSL1344 (pYA-sopENt100-egfp) that harbored the reporter gene
      enhanced green fluorescent protein (egfp) gene. Vero cells were infected with
      DeltacrpDeltaasdSL1344 (pYA-sopENt100-egfp) and the ability of delivery foreign
      antigens was tested via Western blotting analysis. The results of PCR, enzyme
      digestion and sequencing showed that the DeltacrpDeltaasdSL1344 (pYA-sopENt100)
      type III secretion system was constructed successfully. The serotype of
      DeltacrpDeltaasdSL1344 (pYA-sopENt100) was identical to DeltacrpDeltaasdSL1344
      and SL1344. Compared with wild strain SL1344, the biochemical characteristics of
      DeltacrpDeltaasdSL1344 (pYA-sopENt100) had obvious change, but it was basically
      the same with DeltacrpDeltaasdSL1344. The growth speed was much slower than that
      of the wild strain SL1344. The chicken virulence test (LD50) showed that the
      virulence of DeltacrpDeltaasdSL1344 (pYA-sopENt100) was 7*104 times lower than
      SL1344. In addition, we observed the 37 kDa SopENt100-egfp protein in the
      cultured supernatant of DeltacrpDeltaasdSL1344 (pYA-sopENt100-egfp) strain by
      Western blotting analysis. However, both the 37 kDa SopENt100-egfp protein and 27
      kDa EGFP protein were detected in DeltacrpDeltaasdSL1344 (pYA-sopENt100-egfp)
      infected Vero cells. These results demonstrated that the recombinant Salmonella
      typhimurium type III secretion system DeltacrpDeltaasdSL1344 (pYA-sopENt100) was
      successfully constructed, and it should be used as a live vaccine vector for
      expressing foreign genes.

PMID- 29034635
TI  - [Structural regulation by calcium ion in preparing cross-linked enzyme
      aggregates].
AB  - We studied the effect of calcium ion on particle size and pore structure of cross
      linked enzyme aggregates (CLEAs) of glucose oxidase, with activity and stability
      of the enzyme as evaluation criteria. With calcium ion to prepare CLEA
      significantly decreased particle sizes of CLEAs whilst the pore structures of
      CLEAs gradually disappeared with the increase of calcium concentration. When
      glucose oxidase was precipitated at 0.1 mmol/L Ca2+, glucose oxidase in CLEA
      showed the definitive pore structure. Moreover, glucose oxidase activity in CLEA
      with Ca2+ was 1.69 times higher than that without Ca2+. Even at Ca2+ as high as
      1.0 mmol/L, glucose oxidase activity in CLEA was 42% higher than that of CLEA
      without Ca2+. Furthermore, CLEA prepared with 0.1 mmol/L Ca2+ not only exhibited
      higher substrate conversion and operational stability, but also increased the
      maximum reaction speed. Therefore, calcium ion improved the performance of
      glucose oxidase in CLEAs.

PMID- 29034636
TI  - [High-dose heat shock protein gp96 immunization prevents type 1 diabetes via
      inducing regulatory T cells].
AB  - Type 1 diabetes (T1D), the most prevalent human autoimmune disease, occurs in
      genetically susceptible individuals. Regulatory T cells (Tregs) are defective in
      T1D setting. Therefore, efforts to repair or restore Tregs in T1D may prevent or
      reverse this autoimmune disease. Here, we studied the potential role of rgp96 in
      preventing T1D, using non-obese diabetic (NOD) mice as an animal model. High-dose
      rgp96 immunization elicited efficient protection of mice against T1D, as
      evidenced by stable blood glucose, decreased disease incidence. Significantly
      increased CD4+ CD25+ Foxp3+ Tregs were observed in immunized mice. In vitro co
      culture experiments demonstrated that rgp96 stimulation enhanced Treg
      proliferation and suppressive function by up-regulation of Foxp3 and IL-10. Our
      work shows that activation of Tregs by high-dose rgp96 immunization protects
      against T1D via inducing regulatory T cells and provides preventive and
      therapeutic potential for the development of an rgp96-based vaccine against T1D.

PMID- 29034637
TI  - [Development, identification and application of 33 monoclonal antibodies against
      cardiac troponin T].
AB  - The aim of this study is to prepare and characterize cardiac troponin T (cTnT)
      monoclonal antibodies (mAb), and further develop a chemiluminescence quantitative
      detection assay for cTnT. BALB/c mice were immunized with recombinant cTnT
      antigen, and specific mAbs were prepared using conventional hybridoma technique
      and screened by indirect ELISA method. To identify the epitopes, several cTnT
      peptide fragments were synthesized or expressed by genetic engineering. A double
      antibody sandwich ELISA method was used to screen the mAb pairs for cTnT
      detection, and the automatic chemiluminescence detection assay for cTnT was
      developed. In total 220 clinical specimens were used for system comparison
      between our assay and Roche cTnT assay; further performance characteristics was
      evaluated by testing 238 clinical samples and 784 physical examination samples.
      We successfully screened 33 strains of hybridoms against cTnT, and the mAbs'
      epitopes were identified. Mab E16H8 and C8G11 with a detection limit of 10 pg/mL
      cTnT antigen were selected to develop the full automatic chemiluminescence
      quantitative assay. The correlation coefficient of our reagent with Roche's was
      0.959 9, with a coincidence rate of 95%. The assay presented a sensitivity of
      97.5%, and a specificity of 99.15% in detection of clinical samples. The cTnT
      concentration was less than 0.080 6 ng/mL in 99% of general population, which
      agrees with the definition of WHO on patients with acute myocardial infarction
      (AMI). In summary, we developed monoclonal antibodies against predominant
      epitopes for diagnostics of cTnT, and an automatic tubular chemiluminescence
      quantitative detection assay was further developed, which presents a high
      coincidence rate with Roche's.

PMID- 29034638
TI  - [Construction of spider silk functional platform via intein trans-splicing].
AB  - To provide technical support for spider silk functional modification, we
      developed a simple and efficient functional platform via intein trans-splicing.
      Small ubiquitin-related modifier protein (SUMO) was fused to the recombinant
      spider silk protein (W2CT) by peptide bond via S0 split intein Ssp DnaB trans
      splicing, resulting in a protein SUMOW2CT. However, incorporation of exogenous
      protein led to mechanical property defect and lower fiber yield, and also slowed
      down the fiber assembly velocity but no obvious differences in supercontraction
      and chemical resistance when compared with fibers from W2CT (W). SUMO protease
      digestion showed positive results on the fibers, indicating that the SUMO protein
      kept its native conformation and bioactive. Above all, this work provides a
      technical support for spider silk high simply and efficient functionalized
      modification.

PMID- 29034639
TI  - [Optimization of expression conditions and activity identification of hepatocyte
      targeting peptide-human endostatin].
AB  - To obtain sufficient purified and active fusion protein-hepatocyte-targeting
      peptide-human endostatin (HTP-rES), we studied the growth curve and the optimal
      induction timing of BL21/pET21b-HTP-rES. Different conditions of pH value,
      induction time, induction concentration and induction temperature were optimized
      by univariate analysis. After washing, refolding and purifying, the activity of
      fusion protein was identified by flow cytometry and 3-(4,5)-dimethylthiahiazo (-z
      y1)-3,5-di-phenytetrazoliumromide (MTT). Results show that the logarithmic growth
      phase of BL21/pET21b-HTP-rES was from 1.5 h to 3.5 h, the optimum expression
      conditions were pH 8.0, 0.06 mmol/L IPTG, at 42 C for 5 h. The purity of
      inclusion bodies was up to 60% after washing. The purity of target protein was
      more than 95% after refolding and purification. Our findings provide the
      foundation for further biological activity and drug development.

PMID- 29034640
TI  - [Preparation and antioxidant activity detection of collagen peptide from
      Cirrhinus molitorella skin].
AB  - In order to prepare antioxidant peptide through hydrolyzing low-value protein
      resources with bacterial extracellular proteases and to discover novel proteases,
      crude extracellular protease from Pseudoalteromonas sp. SHK1-2 was obtained
      through fermentation which was used to hydrolyze collagen extracted from
      Cirrhinus molitorella skin. Small peptide fraction was isolated from hydrolysate
      by ultrafiltration and Sephadex LH-20 size exclusion chromatography and showed 1,
      1-diphenyl-2-picrylhydrazyl radical scavenging activity (35.6%+/-7%), oxygen
      radical absorbance capacity and inhibition of DNA oxidation damage. The molecule
      weight was 776.2 Da, and amino acid sequence was Thr-Ala-Gly-His-Pro- Gly-Thr-His
      through liquid chromatography mass spectrum. Our findings suggest that peptide
      obtained from low-value protein of fish waste by hydrolysis with bacterial
      protease has antioxidant activity.

PMID- 29034641
TI  - [Establishment of L-periaxin gene knock-out RSC96 cell line].
AB  - Periaxin, a protein of noncompact myelin, is specifically expressed in the
      peripheral nervous system (PNS). There are two protein isoform L-periaxin and S
      Periaxin by alternative splicing of periaxin gene, playing an important role in
      the initiation of myelin formation. So far, 18 different mutation sites in L
      periaxin gene have been found to induce the peripheral demyelinating neurological
      charcot-marie-tooth diseases subtype 4F (CMT4F). The technique of activation of
      transcription activator-like effector nucleases (TALENS) was used to knock out
      the L-periaxin gene in RSC 96 cell line of Rattus. According to the design
      principle, the knock-out site of L-periaxin was assured to NLS domain of L
      periaxin, which is target sequence of left and right arms of TALEN. The knock-out
      vectors of TALEN-L and TALEN-R were established and transfected into RSC96 cell.
      After puromycin screening, L-periaxin was knocked out successfully in RSC96 cell,
      which is confirmed by DNA sequence. The mutation efficiency is 21.6%. S-periaxin,
      not L-periaxin can be detected by Western blotting in L-periaxin gene knock-out
      RSC96 cell. The cell growth rate was decreased and the number of cells in G1
      increased and decreased in S phase in L-periaxin gene knock-out RSC96 cell by
      flow cytometry and MTT assay.

PMID- 29034642
TI  - [Construction of recombinant strains co-expressing PPK and GMAS for the synthesis
      of L-theanine].
AB  - Recombinant strains expressing enzymes for ATP regeneration and L-theanine
      production were constructed and used for the synthesis of L-theanine. The ppk
      gene encoding polyphosphate kinase (PPK) from Rhodobacter sphaeroides and gmas
      gene encoding gamma-glutamylmethylamide synthetase (GMAS) from Methylovorus mays
      were synthesized, and two recombinant plasmids, pETDuet-ppk+gmas and pET21a
      ppk+gmas were constructed for co-expression of PPK and GMAS in Escherichia coli
      BL21(DE3). SDS-PAGE analysis showed that PPK and GMAS were overexpressed in
      soluble form in both recombinant strains. GMAS-PPK obtained from the recombinant
      strain containing pET21a-ppk+gmas was more efficient to synthesize L-theanine.
      After 24 h at 37 C and pH at 7.0, 86.0% yield of L-theanine was achieved with
      catalytic amount of ATP. This study extends the application of enzymatic ATP
      regeneration system. In addition, it provides an efficient method for the
      biosynthesis of L-theanine.

PMID- 29034643
TI  - Epididymo-Orchitis in Bechet's Disease: A Review of the Wide Spectrum of the
      Disease.
AB  - Behcet's disease is a chronic, recurrent, inflammatory disorder characterized by
      orogenital ulcers and skin lesions; serious manifestations also include ocular,
      large vessel, gastrointestinal and neurological involvement. Genetic and unknown
      environmental factors modify the wide clinical spectrum of the disease. During
      the long clinical course of the disease, testicular and epididymal involvement
      has been reported, with scrotal pain and swelling being the most common symptoms.
      In this review, we discuss the various aspects of epididymo-orchitis in Behcet's
      disease patients, and we evaluate the diagnostic approaches as well as the
      empirical therapeutic modalities of this entity.

PMID- 29034644
TI  - The Effect of Eicosapentaenoic Acid on the Serum Levels and Enzymatic Activity of
      Paraoxonase 1 in the Patients With Type 2 Diabetes Mellitus.
AB  - Paraoxonase 1 is known as one of the most important ant oxidative enzymes
      associated with HDL-c, and because of its antioxidant and antiinflammatory
      activities. EPA has the antioxidant, anti inflammatory, antithrombogenic, and
      antiarteriosclerotic properties. Therefore, we investigated the effect of EPA
      supplementation on the serum levels and activity of PON1 in type 2 diabetic
      patients. This study was designed as a randomized, double-blind, and placebo
      controlled clinical trial. Thirty-six patients with type 2 diabetes were given
      written; informed consent randomly was classified into 2 groups. They were
      supplemented with 2 g/day of the capsules of EPA or placebo for eight weeks.
      Blood sample was given for measurement of the serum levels of lipids, the
      activity of PON1, FBS and HbA1c. The patients supplemented with EPA showed a
      significant increase in the serum levels and activity of PON1 and the serum ratio
      of PON1/HDL-c. There were no significant differences between the two groups
      regarding any demographic, clinical or biochemical data, total energy intake, and
      macronutrient intake at the baseline during the intervention, except for a
      significant increase of protein intake and the levels of HbA1c in the placebo
      group, and a significant increase of HDL-c, as well as a slight reduction of
      total cholesterol, LDL-c, TG and FBS in the supplement group. EPA is
      atheroprotective via increase in the serum levels and activity of PON1, as well
      as change in the serum levels of lipids, FBS and HbA1c.

PMID- 29034645
TI  - Peripheral Neuropathy in Multiple Sclerosis: An Electrophysiologic Study in
      Iranian Patients.
AB  - Multiple sclerosis (MS) is the most common cause of disability after trauma in
      young adults in Northern Hemisphere; it imposes a major burden on the affected
      young people. A significant association between MS and demyelinating peripheral
      neuropathy which might be due to common pathogenesis for the central and
      peripheral nerves demyelination has been reported in several studies. We aimed to
      assess if there is any peripheral nervous system involvement in a sample of
      Iranian MS population. Extensive nerve conduction studies (NCS) were conducted in
      20 MS patients according to McDonald criteria, and 20 age and gender matched
      healthy appearing controls. The F-wave ratio was calculated through placing the
      minimum amount of F-wave proximal latency after 10 stimuli and median or tibial
      nerves compound motor action potential (CMAP) proximal latency in the
      corresponding formula. Data were compared between groups. Finally, we found the
      significantly lower median and tibial nerves conduction velocities (NCV) in MS
      patients than healthy controls (P=0.008 and 0.003 respectively, Independent
      Samples t-test). Also, tibial NCV had a significant statistical correlation with
      Kurtzke's expanded disability scale score (EDSS) as patients with higher EDSS had
      lower tibial NCV (Pearson's correlation coefficient, r2=0.8). No statistical
      relationship was found between MS subtypes and NCS parameters. Although we found
      some electrodiagnostic abnormalities in Iranian MS patients in comparison to the
      healthy participants, these differences were small and inconclusive. More
      extensive well-designed electrodiagnostic studies for evaluation of peripheral
      nervous system involvement and its probable pattern in these patients seems to be
      needed.

PMID- 29034646
TI  - Index of Theta/Alpha Ratio of the Quantitative Electroencephalogram in
      Alzheimer's Disease: A Case-Control Study.
AB  - Alzheimer's disease (AD) is a devastating neurodegenerative disorder in human
      beings associated with cognitive, behavioral and motor impairments. The main
      symptom of AD is dementia, which causes difficulties in carrying out daily
      practices. Brain waves are altered in people with AD. Relative indices of brain
      waves can be beneficial in the diagnosis of AD. In this case-control study, 50
      patients with AD and 50 matched healthy individuals were enrolled in case and
      control groups respectively. With recording and analyzing of brain waves with the
      utilization of quantitative electroencephalogram (QEEG), index of theta/alpha
      ratio was assessed in both groups. The index of theta/alpha ratio was
      significantly higher in patients with AD in comparison to healthy individuals
      (P<0.05). Index of theta/alpha ratio obtained by QEEG provides a non-invasive
      diagnostic marker of AD, which may be helpful in identification of non-advanced
      disease in susceptible individuals.

PMID- 29034647
TI  - Seasonality in Violent and Nonviolent Methods of Suicide Attempts: A Cross
      Sectional Study on Systematic Registry Data.
AB  - Little attention has been paid to seasonality in suicide in Iran. Time pattern in
      suicide deaths and suicide attempts for some related factors such as gender,
      mental disorders has been found. In present study, we focus on suicide methods
      and the association with seasonality and other putative covariates such as
      gender. Through a cross-sectional study, overall identified suicide attempts and
      suicide deaths in the province of Ilam from 1 January 2010 and 31 December 2014
      were enrolled. We used Edwards' test for test of seasonality in suicide methods.
      Seasonal effect (peak/trough seasons) and (deaths/attempts suicide) was explored
      by ratio statistics, the null hypothesis being that the attempted suicides in
      each method group are evenly distributed over a year. More suicide attempts by
      hanging 29.4% and self-immolation 41.4% were observed in spring and differ by
      season pattern in both genders. The overall distribution of suicides by violent
      and non-violent methods was (males x2=6.3, P=0.041, females x2=7.7, P=0.021) and
      (males x2=44.5, P=0.001, females x2=104.7, P=0.001), respectively. The peak and
      trough seasons was observed in taking medications and self-poisoning for spring
      and winter. Suicide with alcohol was no differ by season pattern (x2=1.0,
      P=0.460). Suicide in Ilam illustrates a significant seasonality for both violent
      and non-violent methods of suicide, in both genders, the two peaks were observed
      in spring and autumn for violent suicides, and spring and summer in non-violent
      suicides.

PMID- 29034648
TI  - Interactive Multimedia Training in Osteoporosis Prevention of Female High School
      Students: An Interventional Study.
AB  - Given the limitations of traditional teaching methods in the learning process of
      adolescents, this study was designed to investigate the effects of osteoporosis
      prevention training through interactive multimedia method on the degree of
      knowledge and self-efficacy of female high school students. In this
      interventional study which was conducted in 2016 in Fars province, Iran, 120 high
      school students were selected through proportional stratified sampling from
      schools and different classes at first, second, third, and pre-university grades.
      The participants were randomly divided into two groups, each containing 60
      students. Educational interventions for the test group included an interactive
      multimedia CD, and for the control group was an educational booklet. Before and
      one month after the intervention the students' level of knowledge and self
      efficacy was measured. The spss 19 statistical software was used, and descriptive
      and analytical tests were performed to analyze the data. Results showed a
      significant difference in self-efficacy scores after the intervention (P=0.012)
      with the test group obtained a higher self-efficacy score than the control group.
      Also, a significant increase was observed in the knowledge score of both groups
      after the training (P<0.001), but the knowledge score between the two groups was
      not statistically significant (P=0.38) after the intervention. The use of new
      training methods like interactive multimedia CD for public education, particular
      adolescents about health and hygiene is recommended.

PMID- 29034649
TI  - Implementation a Medical Simulation Curriculum in Emergency Medicine Residency
      Program.
AB  - Applying simulation in medical education is becoming more and more popular. The
      use of simulation in medical training has led to effective learning and safer
      care for patients. Nowadays educators have confronted with the challenge of
      respecting patient safety or bedside teaching. There is widespread evidence,
      supported by robust research, systematic reviews and meta-analysis, on how much
      effective simulation is. Simulation supports the acquisition of procedural,
      technical and non-technical skills through repetitive practice with feedbacks.
      Our plan was to induct simulation in emergency medicine residency program in
      order to ameliorate our defects in clinical bedside training. Our residents
      believed that simulation could be effective in their real medical practice. They
      mentioned that facilitators' expertise and good medical knowledge, was the
      strongest point of the program and lack of proper facilities was the weakest.

PMID- 29034651
TI  - Primary Orbital Hydatid Cyst: A Case Report.
AB  - Hydatid cyst is a rare parasitic infection that involved all organs. It caused by
      the larval stage of Echinococcus tapeworms. Hydatid cyst of the head and neck is
      a very rare condition, even in areas where Echinococcus infestation is endemic.
      Orbital hydatid cyst is extremely rare and accounts for less than 1% of all
      hydatid cysts. Herein a 24-year-old man with primary orbital hydatid cyst is
      introduced. He complained from proptosis and diplopia. MRI images revealed a
      lesion with low signal intensity on T1-weighted images and high signal intensity
      on T2-weighted images, which displaced the optic nerve inferiorly and the globe
      inferolateral. The cyst was enucleated via frontotemporal craniotomy and superior
      orbitotomy approach. Histopathological examination of the fluid confirmed the
      diagnosis of hydatid cyst. Treatment of the orbital hydatid cyst is surgical
      excision followed by the systemic use of albendazole.

PMID- 29034650
TI  - A Complicated Case of Resistant Hypertension.
AB  - A 47-year-old woman presented with a history of resistant arterial hypertension,
      associated with disabling headache. She was subjected to an enormous number of
      tests in order to identify an underlying cause of secondary hypertension, such as
      pheochromocytoma or Cushing syndrome, but all the most common causes of secondary
      hypertension were investigated and gradually excluded. Factitious use of
      amphetamine or cocaine was excluded, and therapy compliance was verified by
      witnessed ingestion of drug therapy, in order to rule out Munchausen syndrome.
      The patient underwent a first transcatheter renal denervation (RDN) with poor
      effect on blood pressure (BP) at long term follow up. Because of extremely poor
      control of BP values, a second RDN was performed two years later, again with
      inadequate long term efficacy. Despite an uncontrollable pre-procedural BP, RDN
      had an excessive BP lowering effect in this patient, but only for few months. In
      conclusion, a definitive diagnosis was not performed in our patient, despite an
      extremely deepened examination of the most common cause of refractory
      hypertension.

PMID- 29034652
TI  - White Sponge Nevus: Report of a Case and Review of the Literature.
AB  - White sponge nevus is a rare benign autosomal dominant disorder with variable
      penetrance. It is characterized by asymptomatic white plaques affecting mainly
      the oral mucosa. Careful clinical and histopathological examination is indicated
      to exclude other more serious conditions presenting as oral white lesions.
      Herein, we present a new case of oral white sponge nevus in a 17-year-old Iranian
      male with no familial background.

PMID- 29034654
TI  - Surgical Treatment of Chronic Anal Fissure.

PMID- 29034653
TI  - Successful Delivery in a Woman With Achondroplasia: A Case Report.
AB  - Achondroplasia is an autosomal dominant disease which is characterized by limb
      shortening and narrow trunk, and macrocephaly. Women with achondroplasia suffer
      from infertility, menorrhagia, dysmenorrhoea, leiomyomata and early menopause.
      Our case was a 26-year-old woman with achondroplasia who had scoliosis and
      osteoporosis. She referred to our clinic at 9 weeks of gestation and had all
      screenings completely. She had a single female fetus with no abnormalities. She
      had an emergent due to rupture of membranes at 37 weeks and 3 days under general
      anesthesia. The neonate had no complications. The first minute Apgar score was 9
      and 5th-minute Apgar score were 10. Umbilical artery Ph was 7.26 and birth weight
      was 3140. A woman with achondroplasia could have a normal pregnancy and give
      birth to a healthy term neonate under precise screening.

PMID- 29034655
TI  - Surgery for distal hypospadias: what about the catheter?
AB  - No agreed recommendations exist for timing of urethral stent removal, after
      distal hypospadias surgery. We compared our preliminary case series with outcomes
      from literature: 18/44 patients were treated with catheter and 26/44 without it.
      The surgical outcome was comparable in the two groups. After hypospadias surgery,
      the main advantage of the immediate postoperative catheter removal was the
      shorter hospital stay without negatively affecting the care and home management.

PMID- 29034656
TI  - Guidelines of the Italian Society of Videosurgery in Infancy for the minimally
      invasive treatment of the esophageal atresia.
AB  - Not available.

PMID- 29034657
TI  - Guidelines of the Italian Society of Videosurgery in Infancy for the minimally
      invasive treatment of the ureteropelvic-junction obstruction.
AB  - Not available.

PMID- 29034659
TI  - ?

PMID- 29034658
TI  - Guidelines of the Italian Society of Videosurgery in Infancy for the minimally
      invasive treatment of pediatric nephrectomy and partial nephrectomy.
AB  - Not available.

PMID- 29034660
TI  - ?

PMID- 29034661
TI  - [The 2013-2016 Ebola epidemic in West Africa: critical analysis of a crisis
      primarily social].
AB  - The health crisis in West Africa between 2013 and 2016 is coming to an end. The
      various political, health, and institutional players, involved at various levels,
      either directly or indirectly in the field, have drawn lessons from this dramatic
      event, which comprised a number of management errors. The first article of this
      issue proposes a framework assessment of the concepts and notions involved during
      the 2014-2016 Ebola epidemic in order to identify the modalities of management of
      the crisis. This more objective view is based on our experience in the field
      between 2005 and 2007 following the Ebola epidemic in Central Africa. We propose
      an analysis of these health crises that highlights the errors and inconsistencies
      related to the management of the health emergency. In particular, we discuss the
      meanings of the various terms used to describe Ebola to illustrate the underlying
      ideology and propose a resolutely critical approach to the resulting management,
      emphasizing the importance of the development of contextual and long-term
      approaches, which need to be more frequently taken into account in order to
      improve the management of future crises.

PMID- 29034662
TI  - [The lessons of the Ebola epidemic for a more effective preparedness face to
      health crises].
AB  - Although uncommon, public health crises cause considerable human suffering and
      death and have major political, economic and social impacts. For many years,
      countries have made considerable efforts to prepare for emergencies. The Ebola
      epidemic in West Africa, as well as recent events and emerging public health
      threats force countries to strengthen, adapt or implement their Emergency
      Preparedness Plans. Emergency Preparedness is a difficult process. Some authors
      would even say that it is an impossible mission. What do we mean by preparedness
      ? How can preparedness be evaluated ? What measures must be taken following the
      Ebola crisis ? Preparedness is one of the Emergency Management phases and is
      essential to meet the challenges of future crises. Preparedness still constitutes
      a major challenge for countries and the international community. Based on
      missions conducted in West Africa and on a review of the literature, the authors
      review the concepts of emergency preparedness. In particular, they present
      standards and tools to assess emergency preparedness, using the example of Ebola
      preparedness assessment in West Africa.

PMID- 29034663
TI  - [Anthropology engaged against Ebola (2014-2016): approaches, contributions and
      new questions].
AB  - Anthropologists contributed to the response to the 2014-2016 Ebola outbreak in
      three ways : as Ebola experts, cultural mediators between populations and
      caregivers, and researchers. This article presents a preliminary review of
      approaches, contributions and related issues based on a literature review, case
      studies and debates. The anthropological research discussed in this article
      concerns four themes : epidemiological contexts of transmission ; cultural
      interpretation of illness and social responses ; social construction of
      stakeholders' experience ; critical analysis of public health interventions. In
      addition to insightful contributions, particularly regarding the socio-political
      contexts and their interfaces with global public health measures, anthropologists
      tested forms of communication to facilitate access of public health actors to
      their results. However, these heterogeneous forms of engagement raise a number of
      questions, especially when they reflect anthropological interpretations that
      exclude any critical or reflexive dimension, or when anthropology is considered
      to be similar to social intervention. Nevertheless, anthropological research
      provides a major contribution, which could be even greater if transnational
      networks set up by researchers to analyse the socio-political, economic and
      biocultural dimensions of emerging epidemics are supported in order to improve
      ?preparedness? for future health crises.

PMID- 29034665
TI  - [The origin of Ebola: Biomedical approach versus popular interpretations in
      Macenta, Guinea].
AB  - In December 2013, a two-year-old child died from viral haemorrhagic fever in
      Meliandou village in the South-East of Guinea, and constituted the likely index
      case of a major epidemic. When the virus was formally identified as Ebola,
      epidemiologists started to investigate the chains of transmission, while local
      people were trying to make sense out of these deaths. The epidemic control
      measures taken by national and international health agencies were soon faced by
      strong reluctance and a sometimes aggressive attitude of the affected
      communities. Preliminary ethnographic observations were carried out by ST in
      Macenta (Forest region) during an assignment (October-November 2014) for the
      Global Outbreak and Alert Response Network (GOARN) of the World Health
      Organization. ST carried out participative observation, informal conversations
      and in-depth interviews to identify the rumours and their sources, understand the
      local population's perception and knowledge about the history and origin of the
      Ebola outbreak in Guinea. Epidemiologists involved in the outbreak response
      attributed the first Ebola deaths in the Forest region to the transmission of a
      virus by contact with fluids of patients, but other Guinean citizens believed
      these deaths were caused by the breach of a taboo. The epidemiological and
      popular explanations, mainly evolving in parallel, but sometimes overlapping, are
      driven by different explanatory models, a biomedical model and a traditional
      religious model. The outbreak response must be flexible and must systematically
      document popular discourse(s), rumours, codes, practices, knowledge and opinions
      related to the outbreak and use this information to shape and adapt its control
      interventions.

PMID- 29034664
TI  - [Evolution of Community engagement in the fight against Ebola].
AB  - CONTEXT: Community engagement is one of the most effective approaches to the
      fight against Ebola. It has been shown to be effective in other contexts and was
      implemented in Guinea for two years to reduce the spread of the Ebola Outbreak.
      METHODS: This article is based on a qualitative approach combining several data
      collection methods over a nine-month period in the field : series of formal and
      informal interviews, participating observations, focus groups, comment meetings,
      analysis of reports and follow-up of news on the Ebola Outbreak. These methods
      are designed to more effectively describe community engagement in the fight
      against Ebola in Guinea. RESULTS: Communities were initially subjected to
      coercive methods of prevention and control of Ebola and were stigmatized. This
      context subsequently led to two forms of resistance from communities in relation
      to the actors of prevention : passive and active resistance. The course of the
      epidemic and the determination of the mediators finally succeeded in involving
      the communities in the fight against Ebola, which therefore effectively
      contributed to the end of the epidemic. DISCUSSION: These results demonstrate
      that, as during other epidemics and in other contexts, communities are not
      passive stakeholders in the fight against Ebola. They can be actively involved
      based on their knowledge, but also the attitudes of other actors involved in the
      fight against VME.

PMID- 29034666
TI  - [Respiratory cancers attributable to occupational exposures: what is the cost to
      society in France].
AB  - OBJECTIVE: To estimate the social cost of respiratory cancers attributable to
      occupational risk factors in France in 2010. METHODS: We estimated the number of
      cases of respiratory cancers attributable to each identified occupational risk
      factor according to the attributable fractions method. We also estimated direct
      (costs of hospital stays, drugs, outpatient care) and indirect costs (production
      losses) related to morbidity (absenteeism and presenteeism) and mortality (years
      of lost production). Production losses for paid work and unpaid domestic
      activities were taken into account. RESULTS: The social cost of respiratory
      cancers (lung, larynx, sinonasal, pleural mesothelioma) attributable to exposure
      to asbestos, chromium, diesel engine exhaust, polycyclic aromatic hydrocarbons,
      painting occupations (unidentified carcinogen), crystalline silica, wood and
      leather dust in France in 2010 was estimated to be between ?960 and 1,866
      million. The cost of lung cancer represents between ?804 and 1,617 million. The
      three risk factors with the greatest impact are asbestos (?530 to 890 million),
      diesel engine exhaust (?227 to 394 million), and crystalline silica (?116 to 268
      million). CONCLUSION: These results provide a conservative estimate of the public
      health and economic burden of respiratory cancers attributable to occupational
      risk factors from a societal perspective.

PMID- 29034667
TI  - [To analyse the transferability of an intervention : applying the
      functions/implementation/context model on a diabetes prevention programme].
AB  - INTRODUCTION: A type 2 diabetes primary prevention programme that was shown to be
      feasible and effective in 2003 was transferred to another vulnerable district of
      Reunion Island in 2004, but its short-term effectiveness could not be reproduced.
      Based on this example, this article analyses whether the key
      functions/implementation/context model can be useful to : 1- more accurately
      describe an evaluated intervention ; and 2- identify the factors involved in the
      transferability of this intervention. METHODS: The causality model of the initial
      programme is described. We then identified the key functions (or theoretical
      processes) of this initial programme, implementation of these functions, and the
      context in which the intervention took place. Transfer was analysed by focusing
      on the differences between the initial programme and the transferred programme in
      terms of key functions, implementation and context. RESULTS: The causality model
      involves individual, meso-social, and environmental health determinants. Our
      analysis of programme transfer highlights differences in : key functions (two key
      functions dropped, one key function added, one key function modified),
      implementation (failure to implement, loss/improvement of quality), and context
      (population and socioeconomic level of the district concerned). CONCLUSION: This
      work supports the hypothesis that the key functions/implementation/context model
      can be useful to improve the description of an intervention, and analyse the
      factors involved in its transferability.

PMID- 29034668
TI  - [Health expectations of the inhabitants of a health priority area: a qualitative
      study].
AB  - INTRODUCTION: French law of 4 March 2002 instituted health democracy, making
      health system users a real partner and active stakeholder in the healthcare
      system. This role of health system users must be taken into account particularly
      in health priority areas in order to reduce social inequalities in health. In the
      context of primary care, multidisciplinary clinics would appear to be ideal
      places to develop the expression of health democracy. OBJECTIVE: Identify the
      health expectations of the users of the Villejean clinic (Brittany, France)
      situated in a health priority area. METHOD: Qualitative study based on individual
      and group interviews, conducted with Villejean health system users. Transcripts
      were analysed thematically by a grounded theory approach. RESULTS: Five group
      interviews and twenty-one individual interviews were conducted in 49 users. The
      interviewees described high expectations in terms of a quality relationship with
      healthcare professionals, who were considered to be real educative partners.
      Users also formulated high expectations in relation to facilitated access to
      cares, especially concerning financial aspects. CONCLUSION: Identification of
      users' expectations constitutes the first step in developing a primary care
      health democracy, in which access to care is a major priority. New
      multidisciplinary clinic projects must take these users' expectations into
      account. The creation of user committees could allow the citizen-users' views to
      be really taken into account.

PMID- 29034669
TI  - [The Seintinelles: an innovative approach to promoting Community-Based Research
      and sustaining health democracy in oncology].
AB  - Community-based research drives innovation in major fields of public health,
      HIV/AIDS being the most emblematic example (Demange, Henry & Preau, 2012), and
      hepatitis. However, this type of research appears to be more difficult to develop
      in certain specific diseases, such as cancer (Shankand, Saias & Friboulet, 2009).
      This article proposes various approaches concerning current citizen mobilization
      in relation to cancer research, including potential new levers to the development
      of participative and community-based research based on the recent creation of the
      Seintinelles platform, designed to federate researchers and citizens concerned by
      the problem of cancer. This reflection will be supported by more global issues
      concerning health democracy.

PMID- 29034670
TI  - [Community-based research in therapeutic patient education: practices and
      contributions. A literature review].
AB  - INTRODUCTION: Community-based research (CBR) in health involves both researchers
      and people concerned by the results of the research. It aims to empower
      populations, using their exposure to the phenomenon being studied as a starting
      point. The use of CBR in the field of therapeutic patient education (TPE) is of
      interest, as the two share such characteristics as the desire to foster self
      reliance and participation and a culture of interdisciplinarity. AIM: To
      characterize CBR in the therapeutic patient education field. METHODS: A
      literature search on PUBMED using the keywords ?community-based (participatory)
      research?, ?patient education?, ?self-care? and ?self-management? retrieved 121
      articles. The analysis looked at the type of research, the characteristics of
      both the populations involved and the co-researchers, the collaborative actions
      (analysed using a grid from the literature), and the difficulties in implementing
      these actions. RESULTS: Thirty-one studies were included. Ten consisted of
      methodological studies, which tended to show the added value of collaborating
      with users in implementing TPE programmes compared to standard methods. The
      remaining 21 studies described the co-design and/or co-execution of new
      educational programmes. We identified 5 collaborative actions that involved a
      preparatory phase of the research, and 17 collaborative actions that involved the
      prioritization, conduct, and analysis of the research and dissemination of the
      results. Preventive measures are needed for potential methodological,
      organizational, ethical, and emotional difficulties. DISCUSSION: The 22
      identified actions need to be confirmed by other studies. The analysis grid could
      ultimately become a tool for guiding researchers for their researches within the
      CBR framework.

PMID- 29034671
TI  - [Hepatitis C in prison: an opportunity for healthcare].
AB  - Prison inmates constitute a vulnerable population, in which socially excluded,
      poor and marginalized individuals are overrepresented and infectious diseases are
      more prevalent than in the general population. The poor health of inmates and
      recently released inmates is a rarely studied public health problem. The health
      trajectories of inmates living with the hepatitis C virus is an interesting case
      study to discuss public health interventions in prison. It is presented here as
      part of a socio-anthropological study of inmates and healthcare professionals in
      France. These trajectories shed light on treatment and healthcare experiences,
      within their economic, social, material and institutional constraints. They are
      an integral part of the public debate on prison health in France, comprising two
      prominent positions : the "pathogenic prison" and the "healing prison". These
      extreme positions in the broader context of this debate provide a better
      understanding of the context and obstacles to public health initiatives in prison
      and suggest ways to make them more effective.

PMID- 29034672
TI  - [Motivations and obstacles to occupational disease claims in lung cancer
      patients: an exploratory psychosocial study].
AB  - PURPOSE: The proportion of lung cancers with an occupational origin has been
      estimated to be between 10 and 20%. They are largely under-reported, as 60% are
      not compensated as occupational disease. Although most patients are not familiar
      with the process of compensation, other factors could explain this under
      reporting. The aim of this study was to identify psychosocial factors that could
      impact patients with occupational lung cancer to claim for compensation. METHODS:
      We conducted a case study involving semi-structured interviews with eight lung
      cancer patients enrolled in a cohort designed to systematically screen
      occupational exposures and propose claims for compensation to work-related cancer
      patients. RESULTS: Seven interviewed patients were familiar with occupational
      cancers, but most of them did not believe that past exposure could be related to
      their current disease. Patients associated compensation claims with a long and
      complex procedure for an abstract purpose. Several patients expressed a certain
      attachment to their employers. CONCLUSION: Interviewed patients often considered
      compensation claims to be a grievance procedure against the employers whom they
      did not consider to be responsible for their disease. Lung cancer is itself an
      obstacle to compensation considering the aggressive treatments and related
      adverse events, the poor medium-term prognosis and the predominant role of
      smoking in the etiology of the disease. Patients mentioned the financial
      compensation and the role of healthcare professionals as key elements to motivate
      them to claim for compensation.

PMID- 29034673
TI  - [Occupational exposure to blood among medical students in Casablanca (Morocco):
      Analysis of knowledge and practices].
AB  - Occupational exposure to blood (OEB) is associated with a significant risk of
      transmission of bloodborne viruses to medical students. The objective of this
      study was to evaluate the knowledge and practices of Casablanca medical students
      concerning OEB preventive measures and their behaviour after accidental exposure.
      A cross-sectional study was carried out at the Ibn Rochd University Hospital in
      Casablanca using stratified cluster sampling ; data from this study were
      collected by means of an anonymous self-administered questionnaire. The mean age
      was 22.38 years (SD = 1.69) with a female predominance (56.0%). About 17.5% of
      students had experienced at least one OEB, and only 38.3% were familiar with the
      standard precautions to prevent these accidents. Accidental exposure was
      significantly associated with needle recapping (p = 0.002) and ignorance of
      standard precautions (p = 0.028).These results illustrate the insufficient
      knowledge and poor compliance with preventive measures of occupational exposure
      to blood, indicating the need for awareness-raising and training activities for
      medical students.

PMID- 29034674
TI  - [HAS budget impact analysis guidelines: A new decision-making tool].
AB  - INTRODUCTION: Budget impact analysis (BIA) provides short and medium-term
      estimates on changes in budgets and resources resulting from the adoption of new
      health interventions. OBJECTIVE: The objective of this article is to present the
      main messages of the newly developed French National Authority for Health (HAS)
      guidelines on budget impact analysis : issues, recommendations and perspectives.
      METHODS: The HAS guidelines development process was based on data derived from a
      literature review on BIA (search dates : January 2000 to June 2016), an HAS
      retrospective investigation, a public consultation, international expert advice,
      and approval from the HAS Board and the Economic and Public Health Evaluation
      Committee. RESULTS: Based on its research findings, HAS developed its first BIA
      guidelines, which include recommendations on the following topics : BIA
      definition, perspective, populations, time horizon, compared scenarios, budget
      impact models, costing, discounting, choice of clinical data, reporting of
      results and uncertainty analysis. CONCLUSION: The HAS BIA guidelines are expected
      to enhance the usefulness of BIA as an essential part of a comprehensive economic
      assessment of healthcare interventions, which itself includes cost-effectiveness
      analysis and equity of access to healthcare.

PMID- 29034675
TI  - ?

PMID- 29034676
TI  - Lipid Peroxidation and Its Role in the Expression of NLRP1a and NLRP3 Genes in
      Testicular Tissue of Male Rats: a Model of Spinal Cord Injury
AB  - BAckground: The majority of male patients with spinal cord injury (SCI) suffer
      from infertility. Nucleotide-binding oligomerization domain-like receptors NOD
      like receptors (NLRs) are a kind of receptors that corporate in the inflammasome
      complex. Recent studies have introduced the inflammasome as the responsible agent
      for secreting cytokines in semen. Reactive oxygen species (ROS) is one of the
      elements that trigger inflammasome activation. Genital infections in SCI can lead
      to ROS generation. We investigated the relation between lipid peroxidation and
      inflammasome complex activity in testicular tissue of SCI rats. Methods: Adult
      male rats (n=20), weighting 200-250 g, were included and divided into four
      groups: three experimental groups, including SCI1, SCI3, and SCI7, i.e. the rats
      were subjected to SCI procedure and sacrificed after one, three, and seven days,
      respectively and a control group. We performed a moderate, midline spinal
      contusion injury at thoracic level 10. The animals were anesthetized, and testes
      were collected for measurement of gene expression by real-time PCR. Caudal parts
      of epididymis were collected for malondialdehyde (MDA) measurement. Results: No
      NLRP1a mRNA over expression was seen in the testes of control and SCI groups.
      After seven days from SCI surgery, NLRP3 mRNA expression was significantly
      increased in SCI7 animals (P<=0.05). There was a significant difference in MDA
      level in SCI7 versus control group, as well as SCI1 and SCI3 animals (P<=0.05).
      Conclusion: NLRP3 overexpression occurs due to the increased ROS production in
      testicular tissue of SCI rats.

PMID- 29034677
TI  - Rapid Enrichment and Sensitive Detection of Multiple Metal Ions Enabled by
      Macroporous Graphene Foam.
AB  - Nanomaterials have shown great promise in advancing biomedical and environmental
      analysis because of the unique properties originated from their ultrafine
      dimensions. In general, nanomaterials are separately applied to either enhance
      detection by producing strong signals upon target recognition or to specifically
      extract analytes taking advantage of their high specific surface area. Herein, we
      report a dual-functional nanomaterial-based platform that can simultaneously
      enrich and enable sensitive detection of multiple metal ions. The macroporous
      graphene foam (GF) we prepared displays abundant phosphate groups on the surface
      and can extract divalent metal ions via metal-phosphate coordination. The
      enriched metal ions then activate the metal-responsive DNAzymes and produce the
      fluorescently labeled single-stranded DNAs that are adsorbed and quenched by the
      GF. The resultant fluorescence reduction can be used for metal quantitation. The
      present work demonstrated duplexed detection of Pb2+ and Cu2+ using the Pb- and
      Cu-responsive DNAzymes, achieving a low detection limit of 50 pM and 0.6 nM,
      respectively. Successful quantification of Pb2+ and Cu2+ in human serum and river
      water were achieved with high metal recovery. Since the phosphate-decorated GF
      can enrich diverse types of divalent metal cations, this dual-functional GF
      DNAzyme platform can serve as a simple and cost-effective tool for rapid and
      accurate metal quantification in determination of human metal exposure and
      inspection of environmental contamination.

PMID- 29034678
TI  - Additive Models Reveal Sources of Metals and Organic Pollutants in Norwegian
      Marine Sediments.
AB  - We characterized spatial patterns of surface sediment concentrations of seven
      polychlorinated biphenyls (PCBs), seven polycyclic aromatic hydrocarbons (PAHs),
      three chlorinated pesticides, and five metals in Norwegian waters and Skagerrak.
      In total, we analyzed 5036 concentrations of 22 chemical substances that were
      measured between 1986 and 2014 at 333 sampling sites by means of generalized
      additive models (GAMs). We found that GAMs with organic carbon content of the
      sediment and latitude and longitude as co-variates explained as ca. 75% of the
      variability of the contaminant sediment concentrations. For metals, a
      predominantly hotspot-driven spatial pattern was found, i.e., we identified
      historical pollution hotspots (e.g., Sorfjord in western Norway) for mercury,
      zinc, cadmium, and lead. Highest concentrations of PAHs and PCBs were found close
      to densely populated and industrialized regions, i.e., in the North Sea and in
      the Kattegat and Skagerrak. The spatial pattern of the PCBs suggests the
      secondary and diffuse atmospheric nature of their sources. Atmospheric inputs are
      the main sources of pollution for most organic chemicals considered, but north of
      the Arctic circle, we found that concentrations of PAHs increased from south to
      north most likely related to a combination of coal-eroding bedrock and the
      biological pump. The knowledge acquired in the present research is essential for
      developing effective remediation strategies that are consistent with
      international conventions on pollution control.

PMID- 29034679
TI  - Self-Assembled LiNi1/3Co1/3Mn1/3O2 Nanosheet Cathode with High Electrochemical
      Performance.
AB  - We have fabricated self-assembled LiNi1/3Co1/3Mn1/3O2 nanosheets via a facile
      synthesis method combining coprecipitation with the hydrothermal method. Scanning
      electron microscopic images show that the self-assembly processes for the
      LiNi1/3Co1/3Mn1/3O2 nanosheets depend on the reaction time and temperature. The
      nanosheet structure is uniform, and the width and thickness of the nanosheets are
      in the ranges of 0.7-1.5 MUm and 10-100 nm, respectively. As a cathode material,
      the as-synthesized LiNi1/3Co1/3Mn1/3O2 nanosheets have demonstrated outstanding
      electrochemical performance. The initial specific capacity was 193 mAh g-1, and
      the capacity was maintained at 189 mAh g-1 after 100 cycles at 0.2 C, and 155 mAh
      g-1 at 1 C (after 1000 cycles). The LiNi1/3Co1/3Mn1/3O2 nanosheets have efficient
      contact with the electrolyte and short Li+ diffusion paths, as well as sufficient
      void spaces to accommodate large volume variation. The nanosheets are thus
      beneficial to the diffusion of Li+ in the electrode. The enhanced electrical
      conductance and excellent capacity demonstrate the great potential of
      LiNi1/3Co1/3Mn1/3O2 nanosheets for energy storage applications.

PMID- 29034680
TI  - Boronic Acids as Phase-Transfer Reagents for Fischer Glycosidations in Low
      Polarity Solvents.
AB  - Protocols employing phenylboronic acid as a phase-transfer reagent for Fischer
      glycosidations in low-polarity organic solvents are described. In addition to
      providing rate acceleration, the formation of a substrate-derived boronic ester
      alters the course of the reaction by selective promotion of a furanoside- or
      pyranoside-selective pathway. Computational modeling of the relative energies of
      the glycoside-derived boronic esters provides results that are qualitatively
      consistent with the observed distributions of furanoside versus pyranoside
      products. The boronic esters that are obtained as direct products of these
      reactions serve as protected intermediates for the synthesis of functionalized
      glycosides. Complexation of particular diol groups by the boronic acid also
      enables selective transformations of mixtures of carbohydrates.

PMID- 29034681
TI  - Decarbethoxylative Arylation Employing Arynes: A Metal-Free Pathway to
      Arylfluoroamides.
AB  - An efficient, metal-free decarbethoxylative arylation protocol for the synthesis
      of alpha-aryl-alpha-fluoroamides from fluoromalonamates, under ambient reaction
      conditions using aryne as an electrophilic arylating agent, is reported. This
      decarbethoxylative arylation proceeds under mild conditions and provides a
      practical and effective entry to a wide range of alpha-aryl-alpha
      fluoroacetamides. Interestingly, the use of the tert-butyl ester of
      fluoromalonamate prevented the otherwise rapid decarboxylation step, affording
      the arylated fluoromalonamate in moderate yield.

PMID- 29034682
TI  - Modulated Transport Behavior of Two-Dimensional Electron Gas at Ni-Doped
      LaAlO3/SrTiO3 Heterointerfaces.
AB  - Modulating transport behaviors of two-dimensional electron gases are of critical
      importance for applications of the next-generation multifunctional oxide
      electronics. In this study, transport behaviors of LaAlO3/SrTiO3 heterointerfaces
      modified through the Ni dopant and the light irradiation have been investigated.
      Through the Ni dopant, the resistances increase significantly and a resistance
      upturn phenomenon due to the Kondo effect is observed at T < 40 K. Under a 360 nm
      light irradiation, the interfaces exhibit a persistent photoconductivity and a
      suppressed Kondo effect at low temperature due to the increased mobility measured
      through the photo-Hall method. Moreover, the relative changes in resistance of
      interfaces induced by light are increased from 800 to 6600% at T = 12 K with
      increasing the substitution of Ni, which is discussed by the band bending and the
      lattice effect due to the Ni dopant. This work paves the way for better
      controlling the emerging properties of complex oxide heterointerfaces and would
      be helpful for photoelectric device applications based on all-oxides.

PMID- 29034683
TI  - A Budding-Defective M2 Mutant Exhibits Reduced Membrane Interaction,
      Insensitivity to Cholesterol, and Perturbed Interdomain Coupling.
AB  - Influenza A M2 is a membrane-associated protein with a C-terminal amphipathic
      helix that plays a cholesterol-dependent role in viral budding. An M2 mutant with
      alanine substitutions in the C-terminal amphipathic helix is deficient in viral
      scission. With the goal of providing atomic-level understanding of how the wild
      type protein functions, we used a multipronged site-directed spin labeling
      electron paramagnetic resonance spectroscopy (SDSL-EPR) approach to characterize
      the conformational properties of the alanine mutant. We spin-labeled sites in the
      transmembrane (TM) domain and the C-terminal amphipathic helix (AH) of wild-type
      (WT) and mutant M2, and collected information on line shapes, relaxation rates,
      membrane topology, and distances within the homotetramer in membranes with and
      without cholesterol. Our results identify marked differences in the conformation
      and dynamics between the WT and the alanine mutant. Compared to WT, the dominant
      population of the mutant AH is more dynamic, shallower in the membrane, and has
      altered quaternary arrangement of the C-terminal domain. While the AH becomes
      more dynamic, the dominant population of the TM domain of the mutant is
      immobilized. The presence of cholesterol changes the conformation and dynamics of
      the WT protein, while the alanine mutant is insensitive to cholesterol. These
      findings provide new insight into how M2 may facilitate budding. We propose the
      AH-membrane interaction modulates the arrangement of the TM helices, effectively
      stabilizing a conformational state that enables M2 to facilitate viral budding.
      Antagonizing the properties of the AH that enable interdomain coupling within M2
      may therefore present a novel strategy for anti-influenza drug design.

PMID- 29034684
TI  - Ynol Ethers as Ketene Equivalents in Rhodium-Catalyzed Intermolecular [5 + 2]
      Cycloaddition Reactions.
AB  - The previously unexplored metal-catalyzed [5 + 2] cycloadditions of
      vinylcyclopropanes (VCPs) and electron-rich alkynes (ynol ethers) have been found
      to provide a highly efficient, direct route to dioxygenated seven-membered rings,
      a common feature of numerous natural and non-natural targets and building blocks
      for synthesis. The reactions proceed in high yield at room temperature and
      tolerate a broad range of functionalities. Substituted VCPs were found to react
      with high regioselectivity.

PMID- 29034685
TI  - Improving Performance on Preventive Health Quality Measures Using Clinical
      Decision Support to Capture Care Done Elsewhere and Patient Exceptions.
AB  - Preventive services required for performance measurement often are completed in
      outside health systems and not captured in electronic medical records (EMRs). A
      before-after study was conducted to examine the ability of clinical decision
      support (CDS) to improve performance on preventive quality measures, capture
      clinician-reported services completed elsewhere, and patient/medical exceptions
      and to describe their impact on quality measurement. CDS improved performance on
      colorectal cancer screening, osteoporosis screening, and pneumococcal vaccination
      measures ( P < .05) but not breast or cervical cancer screening. CDS captured
      clinician-reported services completed elsewhere (2% to 10%) and patient/medical
      exceptions (<3%). Compared to measures using only within-system data, including
      services completed elsewhere in the numerator improved performance: pneumococcal
      vaccine (73% vs 82%); breast (69% vs 75%), colorectal (58% vs 70%), and cervical
      cancer (53% vs 62%); and osteoporosis (72% vs 75%) screening ( P < .05). Visit
      based CDS can capture clinician-reported preventive services, and accounting for
      services completed elsewhere improves performance on quality measures.

PMID- 29034687
TI  - Predictors of Placement of Inpatient Palliative Care Consult Orders Among
      Patients With Breast, Lung, and Colon Cancer in a Safety Net Hospital System.
AB  - BACKGROUND: The provision of palliative and end-of-life care to patients who are
      underrepresented and underserved provides unique challenges and opportunities.
      OBJECTIVES: To examine predictors of placement of inpatient palliative care
      consult orders among patients with breast, lung, and colorectal cancer
      hospitalized in a safety net hospital in 2010. METHODS: Simple and multivariable
      logistic regression of data on selected patients with cancer was performed to
      identify predictors of placement of inpatient palliative care consult orders.
      RESULTS: Of 979 patients, 56% had colorectal cancer, 23% had lung cancer, and 21%
      had breast cancer. Of those patients, 16% received an order for inpatient
      palliative care consultation during the study period. Patients who had more than
      20 prescriptions for opioids ordered (adjusted odds ratio [AOR]: 9.10, 95%
      confidence interval [CI]: 4.62-17.95), had an order for a radiation oncology
      consult (AOR: 2.60, 95% CI: 1.50-4.49), or had low albumin (AOR: 2.75, 95% CI:
      4.71) were more likely to have an order for an inpatient palliative care consult
      placed. Race and ethnicity were not statistically significant predictors.
      CONCLUSION: In this cohort of patients in a safety net hospital, markers of pain,
      advanced disease, and poor prognosis were associated with placement of inpatient
      palliative care consult orders.

PMID- 29034688
TI  - End-of-life Characteristics and Palliative Care Provision for Patients With Motor
      Neuron Disease.
AB  - Motor neuron disease (MND) is a neurodegenerative disease and manifested as
      progressive decline in physical, respiratory, swallowing and communication
      function, and ultimately death. Traditional model of care was fragmented and did
      not match with multifacet needs of patients and carers. Furthermore, there could
      be lack of integrated care at end of life for patients with MND in most lower-
      and middle-income countries or in places with inadequate palliative care (PC)
      coverage. In view of this, a special workgroup for patients with MND, which
      includes neurologist, respiratory physician, rehabilitation specialist, and PC
      physician was formed in Hong Kong since year 2011. In various disease phase, each
      specialty team plays a leading role in coordinated care of patients with MND.
      From July 2011 to June 2017, a total of 52 patients with MND were referred for
      PC; 41 deceased patients with MND were included into data analysis. Major cause
      of death remains pneumonia (54.8%) and respiratory failure (40.5%). Most of the
      patients with MND (66.7%) died in acute ward and neurology units, with only 11.9%
      dying in PC units and hospices. The PC team plays a major role in advance care
      planning (ACP), and most patients had their ACP documented at second or third PC
      clinic visit (93.8%). Patients with MND often have limitations in mobility,
      swallowing difficulty, respiratory insufficiency requiring ventilator support,
      and various psychosocial needs. This highlighted the importance of early PC
      referral.

PMID- 29034689
TI  - Autonomy and Withdrawal of Treatment in a Patient With Depression.

PMID- 29034690
TI  - Educator perspectives on the postsecondary transition difficulties of students
      with autism.
AB  - Addressing the challenges of adolescents and emerging adults with autism spectrum
      disorder is crucial to improving the outcomes of these students in the
      postsecondary setting. Although secondary and postsecondary educators and staff
      are critical to helping these students access services, there has been little
      investigation into the perspectives of this stakeholder group, with respect to
      the needs of postsecondary students with autism spectrum disorder. A series of
      focus groups was conducted with secondary and postsecondary educators to
      understand educator perspectives related to the challenges faced by postsecondary
      students with autism spectrum disorder. Competence, autonomy and independence,
      and the development and sustainment of interpersonal relationships emerged as
      primary areas of difficulty and corresponding need. Results suggest that targeted
      interventions addressing these areas should be implemented, prior to and during
      enrollment in a postsecondary setting, to facilitate transition in a
      comprehensive manner.

PMID- 29034691
TI  - Combined transarterial chemoembolization and radiofrequency ablation for small
      treatment-naive hepatocellular carcinoma infeasible for ultrasound-guided
      radiofrequency ablation: long-term outcomes.
AB  - Background Ultrasound (US)-guided radiofrequency ablation (RFA) for small
      hepatocellular carcinoma (HCC) is often infeasible due to unfavorable location
      and poor conspicuity. Those small HCCs can be treated with combined transarterial
      chemoembolization (TACE) and RFA. Purpose To evaluate long-term outcomes of
      combined TACE and RFA for small treatment-naive HCC infeasible for US-guided RFA.
      Material and Methods Between February 2009 and January 2014, 69 patients with
      small (<=3 cm) HCC infeasible for US-guided RFA received TACE and subsequent RFA
      in one session as a first-line treatment. Local tumor progression (LTP), overall
      survival (OS), and event-free survival rates were evaluated. Univariate and
      multivariate analyses were conducted to identify prognostic factors. Results
      Cumulative rates of LTP were 4.4%, 6.8%, 8.2%, 9.5%, and 9.5% at one, two, three,
      five, and seven years, respectively. Cumulative one-, two-, three-, five-, and
      seven-year OS rates were 100%, 95%, 89%, 80%, and 80%, respectively. Cumulative
      one-, two-, three-, five-, and seven-year event-free survival rates were 81%,
      63%, 54%, 31%, and 20%, respectively. No significant prognostic factors for LTP,
      OS, and event-free survival were identified in univariate analysis. Conclusion
      Combined TACE and RFA appears to be an effective treatment for small treatment
      naive HCC infeasible for US-guided RFA in terms of LTP and OS.

PMID- 29034692
TI  - Psychiatric impairment ratings in children and adolescents.
AB  - OBJECTIVES: It is accepted practice in Australia and New Zealand for psychiatric
      impairment rating scales to be applied for persons claiming psychiatric injury.
      These scales were derived for adults, not children. There is less clarity as to
      whether and how these scales may be applied for children claiming psychiatric
      injury. METHODS: We review Australian and New Zealand guidelines and methods for
      assessing permanent psychiatric impairment, as they apply to children and
      adolescents. RESULTS: With significant caution, psychiatric impairment rating
      scales can be administered for children. Guidance and recommendations in this
      regard are provided. For some, the effects of psychiatric injury may not be
      stable, and permanent impairment assessment should be delayed until sufficient
      maturity occurs. CONCLUSIONS: Psychiatric impairment rating scales are widely
      applied for adults claiming psychiatric injury, however caution must be exercised
      when these scales are used in children.

PMID- 29034694
TI  - On being supervised: getting value from a clinical supervisor and making the
      relationship work when it is not.
AB  - OBJECTIVE: The importance of clinical supervision is emphasised in psychiatric
      training programs. Despite this, the purpose and processes of supervision are
      often poorly defined. There is limited guidance available for trainees about
      their role in making supervision work. This paper considers the nature of
      supervision in psychiatric training and provides practical advice to help
      supervisees take active steps to make supervision work. CONCLUSIONS: In obtaining
      value from supervision, the active role of the supervisee in seeking feedback,
      finding value in criticism and building autonomy is emphasised. Additionally, the
      importance of exploring what value a supervisor can offer and maintaining
      realistic expectations is considered. Trainees can benefit from taking an active
      role in planning and managing their supervision to maximise their learning.

PMID- 29034693
TI  - Role of 18F-FDG PET/CT vs CT-scan in patients with pulmonary metastases
      previously operated on for colorectal liver metastases.
AB  - OBJECTIVE: There is currently no conclusive scientific evidence available
      regarding the role of the 18F-FDG PET/CT for detecting pulmonary metastases from
      colorectal cancer (PMCRC) in patients operated on for colorectal liver metastases
      (CRLM). In the follow up of patients who underwent surgery for CRLM, we compare
      CT-scan and 18F-FDG PET/CT in patients with PMCRC. METHODS: We designed the study
      prospectively performing an 18F-FDG PET/CT on all patients operated on for CRLM
      where the CT-scan detected PMCRC during the follow up. We included patients who
      were operated on for PMCRC because the histological findings were taken as a
      control rather than biopsies. RESULTS: Of the 101 pulmonary nodules removed from
      57 patients, the CT-scan identified a greater number (89 nodules) than the 18F
      FDG PET/CT (75 nodules) (p < 0.001). Sensitivity was greater with the CT-scan (90
      vs 76%, respectively) with a lower specificity (50 vs 75%, respectively) than
      with the 18F-FDG PET/CT. There were no differences between positive-predictive
      value and negative-predictive value. The 18F-FDG PET/CT detected more pulmonary
      nodules in four patients (one PMCRC in each of these patients) and more
      extrapulmonary disease in six patients (four mediastinal lymph nodes, one
      retroperitoneal lymph node and one liver metastases) that the CT-scan had not
      detected. CONCLUSION: Although CT-scans have a greater capacity to detect PMCRC,
      the 18F-FDG PET/CT could be useful in the detection of more pulmonary and
      extrapulmonary disease not identified by the CT-scan. Advances in knowledge: We
      tried to clarify the utility of 18F-FDG PET/CT in the management of this
      subpopulation of patients.

PMID- 29034695
TI  - What is the clinical significance of chronic emptiness in borderline personality
      disorder?
AB  - OBJECTIVE: The objective of this study was to review the clinical significance of
      the experience of chronic emptiness in borderline personality disorder (BPD).
      METHODS: A systematic search of the literature was conducted using MEDLINE and
      PubMed, employing search terms including 'emptiness', 'personality disorder' and
      'borderline personality disorder'. The most relevant English-language articles
      and books were selected for this review. RESULTS: Published literature and
      clinical experience suggest that chronic emptiness represents a substantial
      component of the symptom burden experienced by people with BPD, contributes to
      functional impairment and may distinguish BPD from other disorders such as major
      depressive disorder. CONCLUSIONS: Further research will elucidate the
      significance of chronic emptiness with regard to diagnosis, prognosis and
      treatment of BPD.

PMID- 29034697
TI  - Factors influencing black men and their partners' knowledge of prostate cancer
      screening: a literature review.
AB  - : Prostate cancer is the most commonly diagnosed cancer in men in the UK, with 46
      690 new cases in 2014. While there is sufficient research on this topic in the
      USA, there is no review in the UK regarding both black men and their significant
      others' perspective on prostate cancer screening. AIM: To identify and explore
      factors that may influence black men and their significant others' knowledge and
      awareness of prostate cancer screening. METHOD: A literature search revealed
      seven relevant articles. RESULTS: Six of the seven articles were conducted in the
      USA. The results are described using four themes: perception of prostate cancer
      screening, fear, anxiety and discomfort, misinformation about prostate cancer
      screening procedures and communication and decision-making. CONCLUSION: The
      evidence suggests that some black men and their significant others had knowledge
      and awareness of prostate cancer screening. However, their views were influenced
      by misperceptions, misinformation, fear and anxiety around screening procedures
      and mortality. Communication and spousal support were important in decision
      making.

PMID- 29034696
TI  - Development of the Supported Employment, Comprehensive Cognitive Enhancement, and
      Social Skills program for adults on the autism spectrum: Results of initial
      study.
AB  - The population of adults on the autism spectrum continues to increase, and
      vocational outcomes are particularly poor. Longitudinal studies of adults with
      autism spectrum and without intellectual disability have shown consistent and
      persistent deficits across cognitive, social, and vocational domains, indicating
      a need for effective treatments of functional disabilities as each impact
      employment. This initial pilot study is an open trial investigation of the
      feasibility, acceptability, and initial estimates of outcomes for the newly
      developed Supported Employment, Comprehensive Cognitive Enhancement, and Social
      Skills intervention, a manualized "soft skills" curriculum, to enhance both
      cognitive and social development in adults with autism spectrum. A total of eight
      adults with autism spectrum, without intellectual disability (78% males),
      participated in the study. Results support the original hypothesis that adults
      with autism spectrum can improve both cognitive (i.e. executive functioning) and
      social cognitive (i.e. social thinking and social communication) abilities.
      Further Supported Employment, Comprehensive Cognitive Enhancement, and Social
      Skills was found to be feasible, acceptable, and highly satisfactory for
      participants and parents. Employment rates more than doubled post-intervention,
      with an increase from 22% to 56% of participants employed. Conclusion is that
      Supported Employment, Comprehensive Cognitive Enhancement, and Social Skills has
      promise as an intervention that can be easily embedded into exiting supported
      employment vocational training programs to improve cognitive, social, and
      vocational outcomes.

PMID- 29034699
TI  - Valuing what we do.

PMID- 29034698
TI  - An insight into the patient's response to a diagnosis of urological cancer.
AB  - A cancer diagnosis and the patient's response to the news pertains to all types
      of cancer, however, in this article, the focus is on urological cancer. Intrinsic
      to the management of this patient group is the urology multidisciplinary team, in
      which the role of the cancer nurse specialist (CNS) is pivotal. For most people,
      a cancer diagnosis is arguably their worst fear. It is therefore prudent that a
      holistic approach is used when determining care and ensuring that appropriate
      support is forthcoming. This necessitates an assessment of the physical,
      psychological/emotional, psycho-social, spiritual and cultural components of the
      individual's healthcare needs, and accordingly, devising a plan of care to secure
      the best outcomes. This article concentrates on the psychological/emotional
      component. It outlines a case study of a patient's response to the consultant's
      question in the joint consultation clinic, examines the CNS's interpretation and
      understanding of the events, and her perspective on whether factors such as fear,
      anxiety and distress influence the individual's response to the diagnosis, their
      comprehension of information and the messages relayed, and consequently, their
      ability to manage the ensuing issues. It also looks at the support available to
      cancer patients following the receipt of a cancer diagnosis and its efficacy in
      addressing their concerns. Integral to this is effective communication,
      specifically the timely provision of information by health professionals.

PMID- 29034700
TI  - Trust clinical negligence claims: the problem of escalating costs.
AB  - John Tingle, Associate Professor (Teaching and Scholarship), Nottingham Trent
      University, discusses a recent report by the National Audit Office on managing
      the costs of clinical negligence in trusts.

PMID- 29034701
TI  - Urological issues following gender reassignment surgery.
AB  - It has been estimated that 0.2% of the UK population identifies as transgender.
      For those who seek gender reassignment, the pathway can involve the expertise of
      multiple disciplines, including primary care, psychology, endocrinology and
      speech and language therapy. A small but significant number of the transgender
      population will also elect to undergo gender-affirming genital surgery in order
      to achieve gender congruence. In the UK, very few specialist centres provide
      genital gender-affirming surgery for trans-men and women. The population
      accessing these services spans the entire UK, and with such geographical
      dispersion, trans-patients with uro-genital complications after surgery in both
      the short and long term are likely to present locally, with initial
      assessment/management often conducted in a non-specialist setting. This article
      aims to help familiarise nurses with genital gender reassignment/affirming
      surgery and the resultant altered anatomy. It explores the urological issues
      trans-men and women may experience as a consequence of surgery.

PMID- 29034702
TI  - Taking a comprehensive health history: learning through practice and reflection.
AB  - Taking a comprehensive health history is a core competency of the advanced
      nursing role. The purpose of the health history is to source important and
      intimate knowledge about the patient and allow the nurse and patient to establish
      a therapeutic relationship. Reflective practice, a core value of nursing in
      Ireland, means learning from experience. This article demonstrates how a recorded
      comprehensive health history simulation, coupled with reflection, provided
      insight into an advanced nurse practitioner's history-taking skills, thereby
      enhancing clinical practice.

PMID- 29034703
TI  - Managing when a person with dementia comes onto the ward.

PMID- 29034704
TI  - The role of nutrition and hydration in disease prevention and patient safety.
AB  - Omorogieva Ojo, Senior Lecturer in Primary Care at the University of Greenwich,
      O.Ojo@greenwich.ac.uk , looks at the importance of nutrition and hydration across
      healthcare settings.

PMID- 29034705
TI  - Considering the future direction of children's and young people's nursing.
AB  - Sonya Clark, Senior Lecturer in Children's Nursing at Queen's University Belfast,
      Emeritus Professor Alan Glasper, from the University of Southampton and Jim
      Richardson, Senior Lecturer in Children's Nursing at Kingston University and St
      George's, University of London, discuss the concerns of the academic community.

PMID- 29034706
TI  - Chronic lymphocytic leukaemia and secondary skin malignancies.
AB  - Chronic lymphocytic leukaemia (CLL) is a non-Hodgkin lymphoma commonly occurring
      in older adults. Many people with CLL can go for years without requiring
      treatment. However, they have an increased risk of secondary cancers,
      specifically melanoma and non-melanoma skin cancers. Furthermore, these secondary
      cancers are frequently more aggressive in this cohort of patients. Health
      professionals working in haematology, dermatology and general practice have an
      opportunity to educate patients about risk factors and measures to aid
      prevention. Modern technology may assist patients and professionals in the early
      detection of secondary skin cancers, which will lead to expedited treatment and
      better survival outcomes.

PMID- 29034708
TI  - Integrating charity work into our role as future nurses.
AB  - Gabriella Gilbert, a student nurse based in Gibraltar, has done some voluntary
      work that enhanced her understanding of care outside of the acute and primary
      care settings.

PMID- 29034707
TI  - Female genital mutilation: implications for clinical practice.
AB  - Female genital mutilation (FGM) is an established cultural practice in over 30
      countries. It has no health benefits, carries a high risk of physical and
      psychological harm, and is illegal in many countries including the UK. A
      sensitive approach is required, both in the management of complications and
      prevention of this practice. This article discusses the prevalence and
      classification of FGM, and offers practical advice to nurses and midwives
      involved in general and obstetric care. Legal aspects, including safeguarding
      responsibilities and the mandatory duty to report FGM in England and Wales, are
      outlined.

PMID- 29034709
TI  - Advanced wound healing and NPWT: overcoming the challenges.
AB  - Nicholas Bunce, Editor of Nursing and Residential Care, discusses some highlights
      of the recent Hartmann LINK for Wound Healing Congress, which was organised in
      collaboration with the Journal of Wound Care.

PMID- 29034710
TI  - Developing our future leaders: the role of a global mentoring programme.
AB  - Elizabeth Rosser, Deputy Dean (Education and Professional Practice) and Professor
      of Nursing at Bournemouth University, describes the experience of taking part in
      a global mentoring programme.

PMID- 29034711
TI  - Electromagnetically guided bedside placement of post-pyloric feeding tubes in
      critical care.
AB  - Post-pyloric feeding is recommended in critically ill patients with gastro
      intestinal intolerance. However, traditional placement methods are logistically
      difficult and carry potential risks. The authors retrospectively compared the
      position of post-pyloric feeding tubes (PPFTs) using an electromagnetic device
      that demonstrated by X-ray and analysed the complication rates, proportion of
      lung placements avoided and the time taken to establish enteral feeding. Forty
      placements in 37 mechanically ventilated patients were analysed; there was a
      success rate of 87.5%. Sensitivity and specificity were 77% (95% CI 59.9-89.6%)
      and 100% (95% CI 48.0-100%). Five lung placements were identified in real time
      and therefore avoided. The mean (SD) time from PPFT placement to X-ray was 134
      minutes (+/- 139 minutes) and, to feeding, 276 minutes (+/- 213 minutes). In
      conclusion, placement of PPFT using an electromagnetic device carries a high
      success rate, is safe and feasible to undertake at the bedside in mechanically
      ventilated patients.

PMID- 29034712
TI  - BJN Awards 2017: Nutrition Nurse of the Year Runner up.

PMID- 29034713
TI  - It's not epilepsy.

PMID- 29034714
TI  - Giving evidence in court.
AB  - Richard Griffith, Senior Lecturer in Health Law at Swansea University, discusses
      the elements of effective evidence giving when appearing before a court or
      fitness to practise panel.

PMID- 29034715
TI  - Mental health care in prisons.

PMID- 29034716
TI  - How to approach changing jobs.
AB  - Sam Foster, Chief Nurse, Oxford University Hospitals, reflects on the process of
      taking on a new role-from leaving a job to building relationships with new
      colleagues-and on empowering teams to promote staff retention.

PMID- 29034717
TI  - Treatment seeking for problematic pornography use among women.
AB  - Background and aims Previous studies examined psychological factors related to
      treatment seeking for problematic pornography use (PU) among males. In this
      study, we focused on females who seek treatment for problematic PU and compared
      them with non-problematic pornography users with regard to variables related to
      problematic PU. Second, we investigated the relationships between critical
      constructs related to problematic PU with the path analysis method, emphasizing
      the predictors for treatment seeking among women. We also compared our results
      with previous studies on males. Methods A survey study was conducted on 719
      Polish-speaking Caucasian females, 14-63 years old, including 39 treatment
      seekers for problematic PU. Results The positive relationship between the mere
      amount of PU and treatment seeking loses its significance after introducing two
      other predictors of treatment-seeking: religiosity and negative symptoms
      associated with PU. This pattern is different from the results obtained in
      previous studies on males. Discussion Different from previous studies on male
      samples, our analysis showed that in the case of women, mere amount of PU may be
      related to treatment-seeking behavior even after accounting for negative symptoms
      associated with PU. Moreover, religiousness is a significant predictor of
      treatment seeking among women, which may indicate that in the case of women,
      treatment seeking for problematic PU is motivated not only by experienced
      negative symptoms of PU but also by personal beliefs about PU and social norms.
      Conclusion For females, negative symptoms associated with PU, the amount of PU
      and religiosity is associated with treatment seeking. Those factors should be
      considered in treatment.

PMID- 29034718
TI  - The prognostic value of the furosemide stress test in predicting delayed graft
      function following deceased donor kidney transplantation.
AB  - OBJECTIVES AND METHODS: The Furosemide Stress Test (FST) is a novel dynamic
      assessment of tubular function that has been shown in preliminary studies to
      predict patients who will progress to advanced stage acute kidney injury,
      including those who receive renal replacement therapy (RRT). The aim of this
      study is to investigate if the urinary response to a single intraoperative dose
      of intravenous furosemide predicts delayed graft function (DGF) in patients
      undergoing deceased donor kidney transplant. RESULTS: On an adjusted multiple
      logistic regression, a single 100 mg dose of intraoperative furosemide after the
      anastomosis of the renal vessels (FST) predicted the need for RRT at 2 and 6 h
      post kidney transplantation (KT). Recipient urinary output was measured at 2 and
      6 h post furosemide administration. In receiver-operating characteristic (ROC)
      analysis, the FST predicted DGF with an area-under-the curve of 0.85 at an
      optimal urinary output cut-off of <600 mls at 6 h with a sensitivity of and a
      specificity of 83% and 74%, respectively. CONCLUSIONS: The FST is a predictor of
      DGF post kidney transplant and has the potential to identify patients requiring
      RRT early after KT.

PMID- 29034719
TI  - The tailored activity program (TAP) to address behavioral disturbances in
      frontotemporal dementia: a feasibility and pilot study.
AB  - PURPOSE: To explore the feasibility of implementing the Tailored Activity Program
      with a cohort of people with frontotemporal dementia and their carers (dyads).
      METHODS: The Tailored Activity Program is an occupational therapy based
      intervention that involves working collaboratively with family carers and
      prescribes personalized activities for behavioral management in people with
      dementia. Twenty dyads randomized into the study (Tailored Activity Program: n =
      9; Control: n = 11) were assessed at baseline and 4-months. Qualitative analyzes
      evaluated feasibility and acceptability of the program for the frontotemporal
      dementia cohort, and quantitative analyzes (linear mixed model analyzes,
      Spearman's rho correlations) measured the impact of the program on the dyads.
      RESULTS: The Tailored Activity Program was an acceptable intervention for the
      frontotemporal dementia dyads. Qualitative analyses identified five themes:
      "carer perceived benefits", "carer readiness to change", "strategies used by
      carer to engage person with dementia", "barriers to the Tailored Activity Program
      uptake/implementation", and "person with dementia engagement". Quantitative
      outcomes showed an overall reduction of behavioral symptoms (F18.34 = 8.073, p =
      0.011) and maintenance of functional performance in the person with dementia
      (F18.03 = 0.375, p = 0.548). CONCLUSIONS: This study demonstrates the potential
      for using an activity-based intervention such as the Tailored Activity Program in
      frontotemporal dementia. Service providers should recognize that while people
      with frontotemporal dementia present with challenging issues, tailored therapies
      may support their function and reduce their behavioral symptoms. Implications for
      rehabilitation The Tailored Activity Program is an occupational therapy based
      intervention that involves prescribing personalized activities for behavioral
      management in dementia. The Tailored Activity Program is an acceptable and
      feasible intervention approach to address some of the unique behavioral and
      functional impairments inherent in frontotemporal dementia.

PMID- 29034720
TI  - Investigating the neuroanatomical substrate of pathological laughing and crying
      in amyotrophic lateral sclerosis with multimodal neuroimaging techniques.
AB  - OBJECTIVE: Pathological laughing and crying (PLC) is common in several
      neurological and psychiatric diseases and is associated with a distributed
      network involving the frontal cortex, the brainstem and cortico-pontine
      cerebellar circuits. By applying multimodal neuroimaging approach, we examined
      the neuroanatomical substrate of PLC in a sample of patients with amyotrophic
      lateral sclerosis (ALS). METHODS: We studied 56 non-demented ALS patients and 25
      healthy controls (HC). PLC was measured in ALS using the Center of Neurologic
      Study Lability Scale (CNS-LS; cutoff score: 13). All participants underwent 3D-T1
      weighted and 30-directional diffusion-weighted imaging at 3T. Voxel-based
      morphometry and tract-based spatial-statistics analysis was used to examine gray
      matter (GM) and white matter (WM) differences between ALS patients with and
      without PLC (ALS-PLC and ALS-nonPLC, respectively). Comparisons were restricted
      to regions with detected differences between ALS and HC, controlling for age,
      gender, total intracranial volume and depressive symptoms. RESULTS: In regions
      with significant differences between ALS and HC, ALS-PLC patients showed
      decreased GM volume in left orbitofrontal cortex, frontal operculum, and putamen
      and bilateral frontal poles, compared to ALS-nonPLC. They also had decreased
      fractional anisotropy in left cingulum bundle and posterior corona radiata. WM
      abnormalities were additionally detected in WM associative and ponto-cerebellar
      tracts (using a more liberal threshold). CONCLUSIONS: PLC in ALS is driven by
      both GM and WM abnormalities which highlight the role of circuits rather than
      isolated centers in the emergence of this condition. ALS is suggested as a useful
      natural experimental model to study PLC.

PMID- 29034721
TI  - Biological monitoring of exposure to low concentrations of benzene in workers at
      a metallurgical coke production plant: new insights into S-phenylmercapturic acid
      and urinary benzene.
AB  - CONTEXT: Urinary S-phenylmercapturic acid (SPMA) and benzene (U-Ben) are usually
      measured at the end of the work shift (ES), although their kinetic of elimination
      is not clearly known. OBJECTIVE: To investigate SPMA and U-Ben elimination 16 h
      after the ES, in 93 coke production workers exposed to low benzene
      concentrations. MATERIALS AND METHODS: Airborne benzene (A-Ben) was measured by
      passive samplings, while SPMA, U-Ben, methyl-tert-butyl ether (U-MTBE), cotinine
      (U-Cot) and creatinine were determined on urine samples collected at ES and
      before the beginning of the next work shift (next BS). RESULTS: Median A-Ben
      concentrations were 17.2 ug/m3 in the personal and 34.7 ug/m3 in the stationary
      samplings. SPMA was always detectable, whereas U-Ben was below the limit of
      quantification in 26.7% of the ES and 35.6% of the next BS samples, and U-MTBE in
      more than the 80.0% of the samples. At both the sampling times, SPMA and U-Ben
      showed a positive dependence on personal A-Ben, as well as on creatinine and U
      Cot values. DISCUSSION AND CONCLUSION: SPMA and U-Ben at the next BS were
      dependent on the exposure to low benzene concentrations suffered in the previous
      work shift, prompting a reconsideration of the urine sampling time recommended by
      the American Conference Governmental Industrial Hygienists (ACGIH).

PMID- 29034722
TI  - The efficacy of Apaziquone in the treatment of bladder cancer.
AB  - INTRODUCTION: Bladder cancer is nowadays a common tumor. Non-muscle invasive
      bladder cancer (NMIBC) has still chances of recurrence and progression in spite
      of surgery and adjuvant treatments. New therapies are being developed to reduce
      these percentages with less adverse effects - Apaziquone (EO9) is an example.
      Areas covered: A literature search has been performed using Pubmed, UpToDate and
      Google verified information (mainly from Food and Drug Administration and
      Spectrum Pharmaceutics websites). We have included data from the most
      representative clinical trials and reviews published. Expert opinion: Apaziquone
      is considered a promising chemical agent if applied intravesically due mainly to
      its pharmacodynamics and safety profile. There is evidence for this with respect
      to adjuvant chemo ablative therapy and as a post-transurethral resection of
      bladder (TURB) single-dose regimen. As a result, new clinical phase III trials
      are needed both to evaluate its efficacy as an adjuvant therapy in the spectrum
      from intermediate- to high-risk non-muscle invasive bladder cancer and to select
      the most appropriate candidates and treatment schedule. As a conclusion,
      Apaziquone is a good candidate to become a better alternative as an adjuvant
      therapy for the treatment of NMIBC in the near future.

PMID- 29034723
TI  - Response to the Letter to the Editor on: Effect of yoga versus hydrotherapy
      training on health-related quality of life and exercise capacity in patients with
      heart failure: A randomized controlled study.

PMID- 29034724
TI  - Prevention of Mother-to-Child Transmission of HIV in Yaounde: Barrier to Care.
AB  - Most HIV-infected children in Sub-Saharan Africa are born where programs for the
      prevention of mother-to-child transmission of HIV (PMTCT) exist but are not
      universally operational. The expansion of PMTCT programs in Cameroon was among
      the largest in francophone Africa, but despite highly variable estimates of PMTCT
      uptake (ranging from 20% to 66%), it is clear that not enough HIV-infected
      pregnant Cameroonian women benefit from treatment to prevent HIV transmission to
      their children. The reasons why HIV-infected women in Cameroon do not use
      treatments to prevent this transmission remain partially unidentified. We
      conducted a qualitative study of the therapeutic itineraries (treatments taken
      and motivations) followed by HIV-infected pregnant women in Cameroon to
      understand the barriers to accessing high-quality PMTCT care. Here we construct
      the therapeutic itinerary for HIV-infected pregnant women, and identify the
      barriers at each step. Lack of financial independence, personal support, and
      empowering information were the primary obstacles at multiple steps.

PMID- 29034726
TI  - An atypical pseudoaneurysm as complication of prosthetic aortic-valve
      endocarditis.
AB  - Endocarditis of a prosthetic heart valve is a life-threatening condition that is
      associated with high morbidity and mortality. Perivalvular extension in infective
      endocarditis includes complications such as periannular or intramyocardial
      abscesses, pseudoaneurysms and fistulae. The incidence of perivalvular extension
      ranges from 10 to 30% in native valve endocarditis and 30 to 55% in prosthetic
      aortic-valve endocarditis. Herein, we describe a case of a 66-year-old man who
      presented endocarditis of a prosthetic aortic valve complicated by infective
      pseudoaneurysm with localization next to the right coronary sinus of Valsalva.
      Moreover, we underscore the importance of the diagnostic imaging tools options
      and surgical timing.

PMID- 29034725
TI  - Polypharmacy and risk of falls and fractures for patients with HIV infection and
      substance dependence.
AB  - Although people with HIV infection (PLWH) are at higher risk of polypharmacy and
      substance use, there is limited knowledge about potential harms associated with
      polypharmacy such as falls and fractures in this population. The study objective
      was to determine whether polypharmacy, as measured by the number and type of
      medication, is associated with falls and fractures among PLWH and DSM-IV
      substance dependence in the past year or ever injection drug use (IDU). We
      identified the number of medications by electronic medical record review in the
      following categories: (i) systemically active, (ii) non-antiretroviral (non-ARV),
      (iii) sedating, (iv) non-sedating as well as any opioid medication and any non
      opioid sedating medication. Outcomes were self-reported (1) fall/accident
      requiring medical attention and (2) fracture in the previous year. Separate
      logistic regression models were fitted for medications in each category and each
      outcome. Among 250 participants, the odds of a fall requiring medical attention
      were higher with each additional medication overall (odds ratio [OR] 1.12, 95%
      Confidence Interval [CI] = 1.05, 1.18), each additional non-ARV medication (OR
      1.13, 95%CI = 1.06, 1.20), each additional sedating medication (OR 1.36, 95%CI =
      1.14, 1.62), and a non-opioid sedating medication (OR 2.89, 95%CI = 1.06, 7.85)
      but not with an additional non-sedating medication or opioid medication. In
      receiver operating characteristic (ROC) curve analyses, optimal cutoffs for
      predicting falls were: >=8 overall and >=2 sedating medications. Odds ratios for
      fracture in the previous year were OR 1.05, 95%CI = 0.97, 1.13 for each
      additional medication overall and OR 1.11, 95%CI = 0.89, 1.38 for each additional
      sedating medication. In PLWH and substance dependence or ever IDU, a higher
      number of medications was associated with greater odds of having a fall requiring
      medical attention. The association appeared to be driven largely by sedating
      medications. Future studies should determine if reducing such polypharmacy,
      particularly sedating medications, lowers the risk of falls.

PMID- 29034727
TI  - Examining the impacts of health literacy on healthcare costs. An evidence
      synthesis.
AB  - Scholars and practitioners share a significant concern about rising healthcare
      costs. Health literacy is widely presented as a solution to this momentous issue,
      paving the way for a more appropriate access to care and therefore, for cost
      savings. However, to date little is still known about the ultimate effects of
      better health literacy on healthcare costs. Drawing from the findings of a
      systematic literature review which ultimately involved 29 papers retrieved from
      Scopus-Elsevier and PubMed. This manuscript is aimed at shedding light on the
      relationship between health literacy and healthcare costs. The inadequate ability
      of patients to understand health information and to navigate the healthcare
      system was found to be an important predictor of inappropriateness in the access
      to health care. In addition, people living with problematic health literacy are
      discouraged to be engaged in the provision of health services and are expected to
      show poor self-efficacy in dealing with their health-related conditions. From
      this point of view, poor health literate patients are assumed to be at high risk
      of exacerbation of their health problems, which in turn contributes in rising
      healthcare costs. In spite of these findings, both policy makers and
      practitioners seem to overlook the importance of health literacy. Eventually, the
      joint intervention on laws, policies, organizational strategies, and practices is
      crucial to handle the challenges related to limited health literacy.

PMID- 29034728
TI  - The language of percentages: ranking bodies, shaping realities, and limiting
      opportunities.
AB  - PURPOSE: This exploratory study is situated in a critical tradition. It aims to
      describe and analyse the reliance on percentage assessments of functional
      capacity among a group of young adults in rehabilitation after serious motor
      vehicle accidents. METHODS: Qualitative interviews and participant observation.
      Thematic and theoretically informed analysis was carried out. RESULTS: The
      concept of percentages played a significant role in the study participants'
      meaning-making processes as they went through rehabilitation. Percentage scores
      below 100 made a strong impression on them and were associated with strong
      emotions. They also strove to prove their scores wrong, often by attempting to
      function in full time (100%) employment positions. Significantly, many talked as
      if they "were" their percentage scores. CONCLUSIONS: The utility of percentage
      logics is to describe parts of that which is full and whole, and we argue that
      this logic provides for specific and problematic ways of seeing and understanding
      impairment and disability. When scored on hierarchical scales, functional tests
      by necessity rank bodies and bodily functions as better or worse while precluding
      alternative understandings of affected function. Implications for rehabilitation
      Measurements expressed in numbers and percentages are used in rehabilitation by
      professionals to depict and convey functional capacities to patients, but this
      "language" also leaks into the wider context of patients' lives and
      understandings of themselves. The act of measurement may work to rank bodies in
      specific and normative ways that are unable to express difference as a valuable
      instance of human diversity, and may make rehabilitees question whether they are
      complete human beings. Medical professionals should address and take into
      consideration the wider consequences of the act of measurement when they provide
      guidance and support for patients' in their rehabilitation processes.

PMID- 29034729
TI  - Visualization of plaque distribution in a curved artery: three-dimensional
      intravascular ultrasound imaging.
AB  - Intravascular ultrasound (IVUS) imaging provides an excellent tool for evaluation
      of the type, morphology, extent, and severity of an atheromatous plaque. 3 D IVUS
      imaging offers additive information pertaining to morphology of the arterial
      structures and volumetric plaque distributions. A new 3 D IVUS visualization
      technique was developed to provide 3 D structural information of a curved artery.
      A virtual 3 D curved arterial phantom consisting of varying cross-sectional
      shapes, wall thicknesses, and acoustic intensity information was utilized to
      validate the nonlinear interpolation technique to create intermediary 2 D IVUS
      images. IVUS imaging was performed for the iliofemoral arterial segment of an
      atherosclerotic Yucatan miniswine model. These in-vivo IVUS data were utilized
      for intermediary IVUS image generation and volumetric 3 D IVUS visualization.
      Smooth transitional changes of cross-sectional shape, wall thickness and
      grayscale intensity were found between the intermediary images and the original
      arterial phantom slices. The 3 D IVUS imaging of the unfolded curved iliofemoral
      artery provided realistic 3 D luminal surface images of the arteries with
      physiologic grayscale intensity information. This unique 3 D IVUS imaging
      technique may help with assessment of 3 D plaque distribution across the curved
      arterial structure, and improve 3 D visualization of atheromatous components.

PMID- 29034730
TI  - Corydaline inhibits enterovirus 71 replication by regulating COX-2 expression.
AB  - Enterovirus 71 (EV71) is a huge threat to the worldwide public health and there
      is no approved antiviral drug for EV71-induced disease therapy. Corydaline exists
      antiallergic and antinociceptive activities, but the anti-EV71 activity of
      corydaline is still not reported. In this study, corydaline could suppress the
      expression of viral structural and non-structural proteins. Furthermore,
      corydaline inhibits EV71 replication by suppressing the COX-2 expression and the
      phosphorylation of JNK MAPK and P38 MAPK but not ERK MAPK in vitro. Based on
      these findings, corydaline could be a potential lead or supplement for the
      development of new anti-EV71 agents in the future.

PMID- 29034731
TI  - Effects of omega-3 fatty acids on bone turnover markers in postmenopausal women:
      systematic review and meta-analysis.
AB  - AIM: There is conflicting evidence regarding the effects of omega-3 fatty acids
      on bone turnover markers in postmenopausal women. Thus, we systematically
      reviewed the efficacy of omega-3 fatty acids by conducting a meta-analysis of
      available randomized controlled trials. METHODS: PubMed, Embase, Cochrane Library
      and Scopus were searched in December 2016. The standardized mean difference (SMD)
      or weighted mean difference (WMD) and the corresponding 95% confidence intervals
      (CIs) were calculated using a fixed-effects model. RESULTS: Eight trials were
      included in the present meta-analysis. The pooled findings did not identify
      significant decreases in bone-specific alkaline phosphatase (SMD -0.08, 95% CI 
      0.29 to 0.12, p = 0.429) and collagen type I cross-linked C-telopeptide (WMD 0
      ng/ml, 95% CI -0.04 to 0.04, p = 0.899). There was a significant decrease in
      osteocalcin (WMD -0.86 ng/ml, 95% CI -1.68 to -0.04, p = 0.040) as compared with
      control. CONCLUSION: Omega-3 fatty acids reduced postmenopausal women's serum
      osteocalcin. Further well-designed studies are needed to verify the effects of
      omega-3 fatty acids on bone mass density and other bone turnover markers in
      postmenopausal women. CLINICAL TRIAL REGISTRATION NUMBER: CRD42016053219 (
      https://www.crd.york.ac.uk/PROSPERO/ ).

PMID- 29034732
TI  - Pregnancy and Childbearing Among Young Adults Who Experienced Foster Care.
AB  - This study explores rates of early pregnancy and parenthood among a sample of
      young adults ( N = 215), ages 18-22, with a history of foster care. The study
      also compares the educational attainment, financial resources, and homelessness
      experiences of young adults who became parents to those who did not. By age 21,
      49% of the young women became pregnant, and 33% of young men reported getting
      someone pregnant. Over a quarter of participants experienced parenthood, which
      was associated with lower educational attainment, less employment, not having a
      checking or savings account, and a history of homelessness. Gender moderated the
      association between parenthood and employment such that males who were parents
      were more likely than female parents to be employed. Given that these young
      adults were at risk of early pregnancy and parenthood regardless of emancipation
      status and across several racial/ethnic groups, the results suggest a need for
      early pregnancy prevention efforts for all youth with child welfare involvement
      as well as improving resources and support for those who become young parents.

PMID- 29034733
TI  - Mothers' Personal and Interpersonal Function as Potential Mediators Between
      Maternal Maltreatment History and Child Behavior Problems.
AB  - This study examined maternal depressive symptoms, social support, parenting, and
      adult attachment as mediators explaining the relation between maternal childhood
      maltreatment and child behavior in offspring. We assessed a community sample of
      96 mother-child dyads. At child age 16 months, mothers self-reported maltreatment
      history, adult attachment, depressive symptoms, and social support, and maternal
      sensitivity was assessed via 2 hr of direct behavioral observation. Maternal
      reports of child behavior were collected at 5 years. Single and parallel
      mediation models were constructed. Only maternal depressive symptoms mediated the
      relation between maternal maltreatment history and children's internalizing
      problems. Maternal sensitivity emerged as a suppressor variable. With respect to
      the relation between maternal maltreatment history and children's externalizing
      problems, when entered singly, maternal depressive symptoms, social support, and
      avoidant attachment emerged as mediators. When examined in parallel, only
      maternal depressive symptoms and avoidant attachment accounted for unique
      mediating variance. Findings have implications with respect to important maternal
      factors that might be targeted to reduce the probability of maladaptive child
      behavior.

PMID- 29034734
TI  - When Is a Child's Forensic Statement Deemed Credible? A Comparison of Physical
      and Sexual Abuse Cases.
AB  - A large national sample of 4,775 reports of child physical and sexual abuse made
      in Israel in 2014 was analyzed in order to examine whether assessments of
      credibility would vary according to abuse type, physical or sexual, and whether
      child and event characteristics contributing to the probability that reports of
      abuse would be determined as credible would be similar or different in child
      physical abuse (CPA) and child sexual abuse (CSA) cases. Results revealed that
      CPA reports were less likely to be viewed as credible (41.9%) compared to CSA
      reports (56.7%). Multigroup path analysis, however, indicated equivalence in
      predicting factors. In a unified model for both types of abuse, salient
      predictors of a credible judgment were older age, lack of a cognitive delay, and
      the alleged abusive event being a onetime less severe act. Over and beyond the
      effects of these factors, abuse type significantly contributed to the prediction
      of credibility judgments.

PMID- 29034735
TI  - Failure of Outpatient Management With Different Observation Times After Racemic
      Epinephrine for Croup.
AB  - BACKGROUND: Observation is necessary following racemic epinephrine (RE) for
      patients with croup. The ideal length of this observation period is unclear.
      OBJECTIVE: To compare the rate of failed outpatient management utilizing
      different observation times after RE administration for croup. METHODS: We
      performed a retrospective chart review of children with croup who required RE.
      Failure of treatment was defined as requiring a second RE treatment and/or
      returning to the pediatric emergency department for croup symptoms within 24
      hours of discharge. RESULTS: The primary analysis considered patients observed
      between 2.1 and 3 hours compared with those observed for 3.1 to 4 hours. The
      patients in the 2.1- to 3-hour group had a higher rate of treatment failure
      (16.7% vs 7.1%, OR = 2.44, P < .01). CONCLUSIONS: Patients requiring RE for croup
      are more likely to have treatment failure if observed for between 2.1 and 3 hours
      as opposed to 3.1 to 4 hours.

PMID- 29034736
TI  - Family History Collection Practices: National Survey of Pediatric Primary Care
      Providers.
AB  - While family history (FH) collection is a core responsibility of pediatric
      primary care providers (PCPs), few details about this practice are known. We
      surveyed a random national sample of 1200 pediatricians and family medicine
      physicians about FH collection practices. A total of 86% of respondents (n = 289
      pediatricians; n = 152 family medicine physicians) indicated that they collect a
      FH "always" or "most of the time" with 77% reporting collection at the first
      visit, regardless of whether it is a health maintenance or problem-focused visit.
      Less than half ask about relatives other than parents, siblings, or grandparents
      (36.3%). Among respondents, 42% routinely update the FH at every health
      maintenance visit while 6% updated FH at every visit. Pediatric PCPs use a
      variety of methods to collect a FH that is limited in scope and variably updated.
      Our results suggest that interventions are needed to help pediatric PCPs collect
      a systematic, efficient, and updated FH.

PMID- 29034737
TI  - Anti-allergic inflammatory effect of vanillic acid through regulating thymic
      stromal lymphopoietin secretion from activated mast cells.
AB  - Vanillic acid, which is well known as a benzoic acid derivative, has been used as
      a flavouring agent. Currently, we ascertained the therapeutic potential action of
      vanillic acid on allergic inflammatory reaction in human mast cell line, HMC-1.
      Treatment with vanillic acid resulted in a significant decrease in levels of
      thymic stromal lymphopoietin and pro-inflammatory cytokines compared to phorbol
      12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-treated HMC-1 cells.
      In PMACI-stimulated cells, treatment with vanillic acid also dramatically
      inhibited activities of caspase-1 and nuclear factor-kB (p65). Furthermore,
      treatment with vanillic acid suppressed phosphorylation of mitogen-activated
      protein kinases in PMACI-treated HMC-1 cells. Taken together, these findings
      suggest that vanillic acid has a beneficial effect on allergic inflammatory
      disorders.

PMID- 29034738
TI  - Chemodiversity of Nepeta menthoides Boiss. & Bohse. essential oil from Iran and
      antimicrobial, acetylcholinesterase inhibitory and cytotoxic properties of 1,8
      cineole chemotype.
AB  - The essential oil of Nepeta menthoides Boiss. & Bohse., from Iran, was analysed
      by GC/MS. Two types of multivariate analyses were done based on the chemical
      composition of the investigated sample in this study and 12 other samples
      reported in the literature to show the chemodiversity in essential oil
      composition. Antimicrobial, acetylcholinesterase inhibitory and cytotoxic
      activities of the essential oil and its major component were assessed. Twenty-one
      compounds were identified, representing 96.81% of the total oil and the major
      constituent was 1,8-cineole (70.06%). Multivariate analyses revealed two
      chemotypes, i.e. nepetalactone and 1,8-cineole. The essential oil of the sample
      investigated in this study which was a 1,8-cineole chemotype and 1,8-cineole
      showed moderate antimicrobial activity and significantly inhibited the activity
      of acetylcholinesterase enzyme. Cytotoxicity evaluation against three breast
      cancer cell lines showed a potent inhibitory activity. Further investigations are
      necessary to confirm the variety in several populations of N. menthoides.

PMID- 29034739
TI  - Regression of an intramedullary spinal cord metastasis with a checkpoint
      inhibitor: a case report.
AB  - Intramedullary spinal cord metastasis is an increasingly common diagnosis in
      patients with cancer largely owing to new imaging techniques and the increase
      lifespan of patients with malignant tumors. The diagnosis confers significant
      morbidity and a poor prognosis. Mainstay palliative treatment options include
      corticosteroids, fractionated radiotherapy and surgery in select cases. In the
      modern era of immunotherapy for the treatment of several tumor types, the
      efficacy of these agents against parenchymal CNS tumors remains unanswered. Here,
      we report a case of regression of an intramedullary spinal cord metastasis with a
      checkpoint inhibitor.

PMID- 29034741
TI  - Anti-inflammatory effect of methanolic extract of Gmelina arborea bark and its
      fractions against carrageenan induced paw oedema in rats.
AB  - Gmelina arborea has been traditionally used for treatment of abdominal pain,
      burning sensation and as stomachic. The anti-inflammatory effect of aqueous and
      methanol extract of this plant has been studied but detailed investigations on
      anti-inflammatory activity of G. arborea stem bark are still not available.
      Therefore, the present study was designed to evaluate the anti-inflammatory
      activity of methanol extract and its fractions using carrageenan induced paw
      oedema model. Methanol extract at the dose of 500 mg/kg and its ethyl acetate
      fraction at 50 mg/kg showed significant reduction in paw oedema in comparison
      with standard drug. Ethyl acetate fraction was subjected to column chromatography
      which resulted in isolation of a new flavonoid (GM-01). Anti-inflammatory effect
      of methanol extract and its fractions can be attributed to the presence of the
      flavonoid GM-01. Further studies are underway for evaluation of anti-inflammatory
      effect of GM-01 and identification of active constituents present in ethyl
      acetate fraction.

PMID- 29034740
TI  - Efficacy and Safety of the Traditional Herbal Medicine, Gamiguibi-tang, in
      Patients With Cancer-Related Sleep Disturbance: A Prospective, Randomized, Wait
      List-Controlled, Pilot Study.
AB  - BACKGROUND: Sleep disturbance is the second most bothersome symptom in patients
      with cancer, and it can significantly impair their quality of life. The aim of
      this study was to investigate the efficacy and safety of the traditional herbal
      medicine Gamiguibi-tang (GGBT) in patients with cancer-related sleep disturbance.
      METHODS: We conducted a prospective, randomized, wait-list-controlled, open-label
      pilot clinical trial on cancer-related sleep disturbance. Patients with cancer
      experiencing poor sleep quality with a Pittsburgh Sleep Quality Index of at least
      6 were randomly assigned to the GGBT and wait-list groups to receive GGBT and
      conventional care, respectively, for 2 weeks. The primary endpoint was the
      Insomnia Severity Index (ISI) score. Fatigue, depression, and cognitive
      impairment were assessed as the secondary endpoints by using the Brief Fatigue
      Inventory (BFI), Beck Depression Inventory (BDI), and Montreal Cognitive
      Assessment (MoCA). RESULTS: Thirty participants who met the eligibility criteria
      were enrolled. Sleep disturbance assessed using the ISI improved significantly
      more in the GGBT group than in the wait-list group (-5.5 +/- 4.4 vs 0.1 +/- 1.1,
      P < .001). Fatigue level determined using the BFI also improved significantly
      more in the GGBT group than in the wait-list group (-0.8 +/- 0.8 vs 0.0 +/- 0.3,
      P = .002). The BDI and MoCA scores showed no significant changes. Adverse events
      were reported in two patients in the GGBT group and consisted of mild dyspepsia
      and mild edema. CONCLUSION: GGBT may be a potential treatment option for cancer
      related sleep disturbance. Further research is needed to investigate the efficacy
      and safety of GGBT.

PMID- 29034742
TI  - Comparison of Outcomes in Patients With Generalized Ligamentous Laxity and
      Without Generalized Laxity in the Arthroscopic Modified Brostrom Operation for
      Chronic Lateral Ankle Instability.
AB  - BACKGROUND: The arthroscopic modified Brostrom operation (MBO) has been
      frequently used to treat chronic lateral ankle instability (CLAI). However, no
      reports comparing the clinical outcomes between patients with or without
      generalized ligamentous laxity (laxity or no laxity, respectively) currently
      exist. The purpose of this study was to compare the clinical outcomes of the 2
      groups with CLAI. METHODS: Between January 2013 and November 2015, arthroscopic
      MBO was performed on 99 patients with CLAI. Patients were divided into 2 groups:
      the laxity group (24 ankles) and no laxity group (75 ankles). Generalized
      ligamentous laxity was defined as a Beighton score of 4 or more points.
      Evaluation tools included the American Orthopaedic Foot & Ankle Society (AOFAS)
      hindfoot ankle score, a pain visual analog scale (VAS), and talar tilt angle.
      RESULTS: The change in talar tilt angle from preoperative to 12 months
      postoperative was significantly greater in the laxity group (-6.9 +/- 5.2)
      compared with the no-laxity group (-4.2 +/- 4.2) ( P = .03). The final follow-up
      AOFAS hindfoot ankle score and pain VAS in both groups showed improvement
      compared with the preoperative values. CONCLUSION: All groups achieved successful
      clinical and radiological final follow-up outcomes. Arthroscopic MBO should be
      considered a reasonable method in patients who have chronic lateral ankle
      instability, regardless of generalized ligamentous laxity. LEVEL OF EVIDENCE:
      III, comparative study.

PMID- 29034743
TI  - Iloneoside: a cytotoxic ditigloylated pregnane glycoside from the leaves of
      Gongronema latifolium Benth.
AB  - Gongronema latifolium Benth (Asclepiadaceae) is an edible-green-leafy vegetable
      with known medicinal value. A chemical investigation of the 80% methanolic
      extract of the leaves led to the isolation of a new pregnane glycoside:
      iloneoside (3-O-[6-deoxy-3-O-methyl-beta-D-allopyranosyl-(1->14)-beta-D
      oleandropyranosyl]-11,12-di-O-tigloyl-17beta-marsdenin), together with four known
      constituents. Their chemical structures were determined by spectroscopic
      analysis. The isolates were tested for their in vitro growth inhibitory activity
      against human leukemia HL-60 cells. Iloneoside was the most active and gave
      apoptotic response. Molecular docking analysis demonstrated that iloneoside could
      be accommodated within hot spots of anti-apoptotic protein Bcl-2. These results
      suggest G. latifolium as a reliable source of potent anticancer compounds.

PMID- 29034744
TI  - Correction to Oncogenic osteomalacia: role of Ga-68 DOTANOC PET/CT scan in
      identifying the culprit lesion and its management.

PMID- 29034745
TI  - Withanolide production by fungal endophyte isolated from Withania somnifera.
AB  - Withanolides, the secondary metabolite from Withania species is used in Ayurvedic
      medicine and now proved to have potential use in treating cardiovascular,
      Alzheimer's disease, etc. Its production in plants varies between genotypes with
      very low yield. For improved industrial commercialisation, there is a need to
      increase its production. Endophytic fungi are symbiotically associated with
      plants and can synthesise the same bioactive compounds and natural products as
      their host plant. There are no reports available on withanolide-producing
      (endophytic) fungi. The present study identified an endophytic fungus
      (Taleromyces pinophilus) from leaves of Withania somnifera which produces
      withanolides in the medium. The structure of withanolide was confirmed by 1H NMR,
      LC-MS analyses and quantified by HPLC analysis. The fungus produces high amount
      of withanolide when compared to leaf and root of W. somnifera. The fungus can be
      exploited to produce the withanolide to meet its demand.

PMID- 29034746
TI  - Clinical characteristics of acute fatty liver of pregnancy in a tertiary
      Indonesian hospital.
AB  - Acute fatty liver of pregnancy (AFLP) is a rare, often autosomal recessive
      disorder with a major risk for maternal and perinatal mortality and morbidity. In
      order to achieve a more favorable outcome, awareness of its clinical signs and
      symptoms and early recognition are of pivotal importance. Over a 5-year period 18
      patients were diagnosed with AFLP (one twin, 19 babies). The most common sign and
      symptoms were jaundice, hypoglycemia, nausea and vomiting, encephalopathy, and
      hypertension. Abnormal laboratory test results included: elevated total/
      conjugated (direct) bilirubin, AST, ALT, PT, APTT, creatinine, leukocyte count,
      and hypoalbuminemia. Maternal and fetal mortality rate was high: 66.7% resulted
      in a maternal death and 57.9% in an intrauterine fetal demise (IUFD). The number
      of complications was found to correlate with maternal death (p = 0.042).
      Surviving AFLP patients had <= 3 complications, while patients with > 3
      complications on presentation had a high risk of maternal death (OR = 5.0; 95%
      CI: 0.55-45.4). The presence of hypertension significantly increased the risk of
      maternal death (OR: 24.5; 95% CI: 1.1-542.8; p = 0.01). The risk of IUFD was
      primarily related to gestational age at delivery and birth weight. The high rate
      of jaundice as presenting symptom of AFLP suggests that Indonesian primary
      maternity care providers may often miss its important earlier signs and symptoms,
      in particular de-novo onset of nausea and vomiting in late pregnancy.

PMID- 29034747
TI  - Long-term supplementation of Rhodiola kirilowii extracts during pregnancy and
      lactation does not affect mother health status.
AB  - Antibiotics treatment during pregnancy and lactation is problematic. The
      alternative to the antibiotic treatment is the use of plant-derived supplements,
      which stimulate immune system to prevent and eliminate bacterial infection. Here,
      we evaluated the effect of long-term use of Rhodiola kirilowii on the health of
      mouse mothers. Pregnant mice were fed daily, for whole pregnancy and for 28 days
      after giving birth, with Rhodiola kirilowii water (RKW) or hydroalcoholic extract
      (RKW-A) (at 20 mg of extracts/kg). The control group received sterile water.
      There was no significant change in the total body weight and selected organs
      weight and in the status of macroscopically evaluated liver, spleen, kidney,
      brain, and eyes, between the Rhodiola kirilowii groups and the control group.
      There was also no change in hematological parameters and components of adaptive
      immunity (level of CD3+, CD4+, CD8+, CD19+, CD335+ cells). Mice fed with RKW
      extracts exhibited lower percentage of oxidative burst in the granulocytes. In
      contrast, the supplementation with RKW-A extract caused increase in the
      percentage of granulocytes in the blood and the percentage of monocytes with
      oxidative burst. Other studied components of innate immunity were unaffected.
      Minor effect on the innate immunity and lack of side effects on hematological
      parameters and components of immunological system of mouse mothers indicates that
      both water and 50% hydroalcoholic extracts of Rhodiola kirilowii (in
      concentration 20 mg/kg per day) could be used as an immunostimulators during
      pregnancy and nursing. However, to fully assess the effects of Rhodiola kirilowii
      extracts on the mother and offspring health, further studies in mouse and large
      animal models and clinical studies in humans are necessary.

PMID- 29034748
TI  - Demographic and neonatal risk factors for childhood asthma in the USA.
AB  - OBJECTIVE: Asthma is the most common chronic condition diagnosed among children
      worldwide according to the World Health Organization (WHO). This study evaluated
      on a longitudinal basis prospectively collected medical records for demographic
      and neonatal information among United States (US) children diagnosed with
      childhood asthma in comparison to controls. DESIGN: The Vaccine Safety Datalink
      (VSD) database was examined to identify cases (n = 5907) diagnosed with
      International Classification of Disease, ninth revision (ICD-9) healthcare
      provider diagnosed childhood asthma (493.xx) and controls (n = 11,662). PATIENTS:
      All cases and controls were health maintenance organization (HMO)-enrolled from
      birth until diagnosis or sufficient time to ensure that they were unlikely to
      receive a diagnosis, respectively. MAIN OUTCOME MEASURES: Child's gestational age
      in weeks at birth, birth weight in grams, maternal age in years at birth,
      Appearance-Pulse-Grimace-Activity-Respiration (APGAR) score at 1 minute and 5
      minutes following birth, gender, and race. RESULTS: The study results revealed
      childhood asthma was diagnosed significantly more frequently among males than
      females, and significantly more frequently among minority populations (Black >
      Hispanic > Native American > Asian) than White populations. Cases diagnosed with
      childhood asthma had significantly decreased mean values for the following
      neonatal risk factors: gestational age, maternal age, birth weight, and APGAR
      scores at 1 and 5 minutes following birth in comparison to controls. CONCLUSIONS:
      This study offers healthcare providers important demographic and neonatal factors
      significantly associated with childhood asthma, and should help aid in the early
      diagnosis and treatment of childhood asthma.

PMID- 29034749
TI  - Screening of older patients for atrial fibrillation in general practice: Current
      evidence and its implications for future practice.
AB  - BACKGROUND: Individuals with atrial fibrillation (AF) face a fivefold increased
      risk of ischaemic stroke compared with those without the condition. Recent
      studies suggest that individuals with asymptomatic AF also face an increased risk
      of ischaemic stroke, but their condition is often not recognized and diagnosed
      until an ischaemic stroke event has occurred. Identification of individuals with
      undiagnosed AF at increased risk for stroke is critical in promoting optimal
      intervention with anticoagulants. OBJECTIVES: In this narrative review, we
      consider the benefits and limitations of various proposed screening strategies,
      whether single or multiple time-points, in addition to devices for implementation
      in the primary care setting. OUTCOMES: Opportunistic screening via pulse
      palpation with subsequent referral for 12-lead electrocardiogram testing has been
      shown to cost-effectively identify individuals with asymptomatic AF. Some
      handheld devices suitable for use in primary care settings are now available and
      may facilitate screening of large cohorts of individuals considered to be at
      increased risk of AF, such as those aged >=65 years or those diagnosed with or
      undergoing monitoring for hypertension. CONCLUSIONS: It was determined that
      improved detection and diagnosis of AF, combined with appropriate anticoagulation
      strategies, will be crucial for improving stroke prevention and reducing its
      associated social and economic costs.

PMID- 29034750
TI  - Parallel vertical compression sutures to control bleeding in cases of placenta
      previa and accreta.
AB  - OBJECTIVE: To evaluate the effectiveness of full-thickness vertical compression
      suture and intrauterine catheter in cases with placenta previa/accreta. STUDY
      DESIGN: This study was conducted on Obstetrics and Gynecology emergency unit of
      Sohag University Hospital. Two longitudinal parallel full-thickness suture was
      taken using delayed absorbable suture (No. 2 Vicryl...) the entry of needle
      through anterior wall of lower uterine segment just above the internal os 2-3 cm
      medial to lateral aspect of lower uterine segment then completely piercing the
      posterior wall and then return from posterior wall to anterior wall 1-2 cm below
      incision line of the uterus. Another suture was taken in other side in the same
      manner. The Foley's catheter was inserted through the incision line into the
      cervix and balloon was inflated by 20-30 cc saline. RESULTS: Two hundred and
      seventy-eight cases were included in the research. There were 107 cases without
      significant bleeding from lower uterine segment and no maneuver was needed. The
      remaining 171 cases were managed by vertical compression suture and intrauterine
      Foley's catheter which was successful in 168 cases (98.2%) to stop the bleeding.
      Only three cases cesarean total hysterectomy was needed. CONCLUSIONS: Vertical
      lateral compression sutures with inserting inflated balloon of Foley's catheter
      is an effective method for controlling bleeding in cases of placenta
      previa/accreta.

PMID- 29034751
TI  - Less than two versus greater than two hour invasive strategy in non-ST elevation
      myocardial infarction: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Optimal timing for an invasive strategy in non-ST elevation
      myocardial infarction (NSTEMI) is unclear. Whether clinical outcomes are improved
      with a less than two (LT2) compared with greater than two hour (GT2) invasive
      strategy remains to be determined. We performed a meta-analysis of randomized
      controlled trials (RCTs) comparing LT2 vs GT2 for NSTEMI. METHODS: A
      comprehensive literature search for RCTs comparing LT2 vs. GT2 in NSTEMI patients
      was performed. Three eligible studies consisting of 1,075 patients (LT2: 537,
      GT2: 538) with NSTEMI were identified. Follow-up ranged from 1 to 12 months.
      RESULTS: Time from randomization to sheath insertion ranged from 0.5-2.2 and 14.0
      85.0 hours in the LT2 and GT2 groups. More percutaneous coronary interventions
      and fewer coronary artery bypass grafting were performed in the LT2 vs. GT2
      group. There was no significant difference in all-cause mortality, myocardial
      infarction (MI), and major bleeding between the two groups. LT2 was numerically,
      but not statistically superior to GT2 at preventing recurrent ischemia/urgent
      revascularization/refractory ischemia. CONCLUSION: Our meta-analysis found no
      significant difference in outcomes between less than two versus greater than two
      hours invasive strategy for NSTEMI. The differences observed in the mode of
      revascularization according to timing of catheterization deserve further study.

PMID- 29034752
TI  - Effect of basic fibroblast growth factor on radiation-induced oral mucositis in
      male Syrian hamsters.
AB  - PURPOSE: Oral mucositis is a frequent and dose-limiting side effect of
      radiotherapy or chemotherapy in cancer patients. We investigated the effect of
      basic fibroblast growth factor on radiation-induced oral mucositis in male Syrian
      hamsters. METHOD: Oral mucositis was induced in male Syrian hamsters by a single
      dose of 30-Gy irradiation. Eight days after irradiation, treatment with gel
      containing trafermin (basic fibroblast growth factor) at 1 or 10 MUg up to day-21
      was initiated. Re-epithelialization was graded using a six-point scoring system
      for oral mucositis. Samples of hamster cheek pouches were removed for
      histopathologic analyses and immunohistochemistry. RESULTS: The oral-mucositis
      score decreased in a dose-dependent manner upon trafermin treatment. Trafermin
      (10 MUg) improved oral mucositis significantly compared with vehicle.
      Histopathology revealed that the degree of re-epithelialization was improved by
      treatment with trafermin (10 MUg) compared with treatment with vehicle.
      CONCLUSIONS: Administration of trafermin (10 MUg) can prevent mucosal damage to
      hamster cheek pouches induced by irradiation.

PMID- 29034753
TI  - Ataxia telangiectasia syndrome: moonlighting ATM.
AB  - INTRODUCTION: Ataxia-telangiectasia (A-T) a multisystem disorder primarily
      characterized by cerebellar degeneration, telangiectasia, immunodeficiency,
      cancer susceptibility and radiation sensitivity. Identification of the gene
      defective in this syndrome, ataxia-telangiectasia mutated gene (ATM), and further
      characterization of the disorder together with a greater insight into the
      function of the ATM protein have expanded our knowledge about the molecular
      pathogenesis of this disease. Area covered: In this review, we have attempted to
      summarize the different roles of ATM signaling that have provided new insights
      into the diverse clinical phenotypes exhibited by A-T patients. Expert
      commentary: ATM, in addition to DNA repair response, is involved in many
      cytoplasmic roles that explain diverse phenotypes of A-T patients. It seems
      accumulation of DNA damage, persistent DNA damage response signaling, and chronic
      oxidative stress are the main players in the pathogenesis of this disease.

PMID- 29034754
TI  - An Unusual Cause of Granulomatous Ileitis - With a Brief History of the Pathology
      of Typhoid.

PMID- 29034755
TI  - The alliance with expanding blood volume and correcting anemia is an effective
      therapeutic measure for the adult anemia patients of acute cerebral infarction.
AB  - : Purpose/aim of the study: Various factors are believed to be involved in the
      etiology of cerebral infarction. Anemia has been shown to deteriorate in
      association with ischemic stroke. However, the exact clinical association between
      anemia and ischemic stroke still remains unclear. We evaluated the clinical
      features of adult anemia patients with acute cerebral infarction and seek a
      better treatment different from the other causes of cerebral infarction, and to
      provide a reference for the diagnosis and treatment of these anemia patients with
      acute cerebral infarction. METHODS: Thirty-two adult patients of acute cerebral
      infarction with anemia were included in this study. A primary discharge diagnosis
      of acute cerebral infarction with anemia was done, and all subjects were
      evaluated as retrospective data. The clinical features were analyzed. A chi
      square test was used to analyze the associations between different variables.
      Therapeutic interventions and outcomes were analyzed under t-test, compared
      between the two groups. RESULTS: The NIHSS score in the patients with the
      administration of EBV/CA (Expanding blood volume and correcting anemia) more
      lowed than Non-EBV/CA in 7 days and 14 days after initial hospitalization. The
      mRS score in the patients with the administration of EBV/CA also more lowed than
      Non-EBV/CA in 14 days. Moreover, the correlation between Hb-serum-level and NIHSS
      scores in the time of initial hospitalization is negative significantly.
      CONCLUSIONS: Anemia is associated with increased neuronal damage and
      deterioration of acute cerebral infarction in the adults. Expanding blood volume
      and correcting anemia are effective therapeutic measures in the adult patients of
      acute cerebral infarctions with anemia.

PMID- 29034756
TI  - A prediction model for early death in non-small cell lung cancer patients
      following curative-intent chemoradiotherapy.
AB  - BACKGROUND: Early death after a treatment can be seen as a therapeutic failure.
      Accurate prediction of patients at risk for early mortality is crucial to avoid
      unnecessary harm and reducing costs. The goal of our work is two-fold: first, to
      evaluate the performance of a previously published model for early death in our
      cohorts. Second, to develop a prognostic model for early death prediction
      following radiotherapy. MATERIAL AND METHODS: Patients with NSCLC treated with
      chemoradiotherapy or radiotherapy alone were included in this study. Four
      different cohorts from different countries were available for this work (N =
      1540). The previous model used age, gender, performance status, tumor stage,
      income deprivation, no previous treatment given (yes/no) and body mass index to
      make predictions. A random forest model was developed by learning on the Maastro
      cohort (N = 698). The new model used performance status, age, gender, T and N
      stage, total tumor volume (cc), total tumor dose (Gy) and chemotherapy timing
      (none, sequential, concurrent) to make predictions. Death within 4 months of
      receiving the first radiotherapy fraction was used as the outcome. RESULTS: Early
      death rates ranged from 6 to 11% within the four cohorts. The previous model
      performed with AUC values ranging from 0.54 to 0.64 on the validation cohorts.
      Our newly developed model had improved AUC values ranging from 0.62 to 0.71 on
      the validation cohorts. CONCLUSIONS: Using advanced machine learning methods and
      informative variables, prognostic models for early mortality can be developed.
      Development of accurate prognostic tools for early mortality is important to
      inform patients about treatment options and optimize care.

PMID- 29034757
TI  - Nano alterations of membrane structure on both gamma-irradiated and stored human
      erythrocytes.
AB  - PURPOSE: Storage and ionizing radiation of human red blood cells (RBC) produce
      alterations on RBC membranes and modify their normal shape and functionality. We
      investigated early morphological and biochemical changes in RBC due to those
      stressing agents at the nanoscale level and their impact on blood quality.
      MATERIALS AND METHODS: Whole blood samples from healthy donors were gamma
      irradiated with 15, 25, 35, and 50 Gy. Non-irradiated and non-stored RBC were
      used as control samples. Irradiated blood samples were stored separately at 4 
      degrees C and analyzed immediately and after 5 and 13 d. Atomic force microscopy
      (AFM), osmotic fragility and Raman spectroscopy were used to detect morphological
      and biochemical changes. RESULTS: RBC function is challenged by both irradiation
      and storage. The storage procedure caused nanometric variations over the surface
      of RBC membrane for both irradiated and non-irradiated cells. The membrane of RBC
      became more fragile, while the biochemical fingerprint of hemoglobin (Hb)
      remained unaltered. CONCLUSIONS: Our work shows that the irradiation procedure
      leads to an increase in the number and size of nanovesicles along with the dose.
      The functionality of RBC can be affected from changes in the roughness, becoming
      more fragile and susceptible to breakage.

PMID- 29034758
TI  - Feasibility study on the use of gold nanoparticles in fractionated kilovoltage X
      ray treatment of melanoma.
AB  - PURPOSE: Despite the high radioresistance of melanoma, unresectable lesions can
      be subjected to radiation treatment with the use of gold nanoparticles (AuNPs) as
      a dose-enhancing agent preferentially loaded on these lesions. The modality of
      single high-dose treatment has been investigated to confirm its therapeutic
      efficiency for AuNP-treated melanoma cells. This study explores the feasibility
      of utilizing AuNPs in fractionated radiation therapy of melanoma for further
      therapeutic gain. MATERIALS AND METHODS: The responses of human skin melanoma
      cells to 150-kVp X-ray exposure at 2 and 4 Gy were assessed by quantify gamma
      H2AX expression and clonogenic survival, with or without 320 MUM of 50 nm AuNP
      treatment in a culture medium. The influence of AuNPs on cell cycle distribution
      was observed before irradiation and during 3 d period after irradiation. RESULTS:
      The AuNP treatment of melanoma cells influenced the cellular response to
      kilovoltage X-rays to similar extents in terms of the percentage of gamma-H2AX
      positive cells and the fractional loss of clonogenicity. Without radiation
      exposure, AuNPs reduced the portion of melanoma cells at the G2/M phase from 11
      to 7%. After irradiation, the progression of the melanoma cells treated with
      AuNPs toward the G2/M phase was more rapid than that of the AuNP-free cells, and
      the release of the former from the G2/M phase was slower than that of the latter.
      At 24 h after irradiation with AuNPs, the cell cycle was rearranged in a pattern
      that increased the vulnerability of the cells to radiation damage. CONCLUSIONS:
      In addition to the benefit of AuNP treatment to the control of melanoma in single
      high-dose treatment, further therapeutic gain is expected through fractionated X
      ray treatment that involves daily exposure. The AuNP-treated melanoma cells of an
      increased portion in the radiosensitive G2/M phase following a fractionated dose
      delivery would respond to the next treatment with an enhanced chance of
      clonogenic death.

PMID- 29034759
TI  - Tale of rudimentary horn pregnancy: case reports and literature review.
AB  - Rudimentary horn pregnancy (RHP) is a rare form of pregnancy in a rudimentary
      uterine horn with a reported incidence of 1 in 76,000 and 1 in 150,000. A
      significant number of cases is diagnosed only following rupture of the RHP with
      an estimated maternal mortality rate of 0.5%. Early diagnosis can help in
      planning management before its rupture and allows for surgical treatment using
      laparoscopy.

PMID- 29034760
TI  - Correction to: The Wheelchair Use Confidence Scale: Italian translation,
      adaptation, and validation of the short form.

PMID- 29034761
TI  - Knowledge and attitude of mothers regarding infant hearing loss in Changsha,
      Hunan province, China.
AB  - OBJECTIVE: The objective of this study was to explore the knowledge and attitude
      among mothers of newborns regarding infant hearing loss (HL) in Changsha, Hunan
      province, China. DESIGN: A questionnaire including 18 items was given to mothers.
      STUDY SAMPLE: A total of 115 mothers participated in the study. RESULTS: Seven
      risk factors for hearing loss were identified correctly by above 60% of
      respondents and the top three were prolonged noise (88.7%), high fever (82.6%)
      and ear discharge (82.6%). Poor knowledge was demonstrated on risk factors
      jaundice (20.0%), measles (22.6%), convulsion (33.0%) and traditional Chinese
      medicine (39.1%). Maternal knowledge scores in identification and intervention
      (2.68 +/- 0.31) was slightly higher than the score in risk factors (2.47 +/-
      0.34). Ninety-nine per cent of the mothers expressed the willingness to test
      baby's hearing soon after birth and concern about hearing. CONCLUSIONS: Mothers
      were concerned about baby's hearing and the attitude was positive. However, the
      correct recognition rate towards some risk factors for HL was low. Action needs
      to be taken to raise awareness about ear and hearing care, prevent HL caused by
      preventable causes and prompt early identification, early diagnosis and
      intervention of HL.

PMID- 29034762
TI  - Exploring the cause of early miscarriage with SNP-array analysis and karyotyping.
AB  - OBJECTIVE: The aim of this study is to explore the cause of miscarriage,
      providing risk assessment to guide the next pregnancy. METHODS: Four hundred
      eighty-four products-of-conception (POC) samples were analyzed by single
      nucleotide polymorphism (SNP) array, and peripheral blood samples of couples were
      collected for karyotyping or fluorescence in situ hybridization (FISH) analysis.
      RESULTS: Four hundred sixty-eight of the 484 (96.7%) fresh POC samples were
      successfully analyzed using SNP-array. The rate of clinically significant
      chromosomal abnormalities were 58.3% (274/468), in which rates of aneuploidy,
      polyploidy, partial aneuploidy, uniparental isodisomy (isoUPD), and pathogenic
      microdeletion/microduplication were 43.4% (203/468), 8.8% (41/468), 3.6%
      (17/468), 1.9% (9/48), and 0.9% (4/468), respectively. The percentage of
      embryonic chromosomal abnormalities significantly increased with maternal age of
      patients older than 35 years old. Among 468 couples, 12 major chromosomal
      rearrangements were detected by G-banding, including nine reciprocal
      translocations, two Robertsonian translocations, and one superfemale.
      CONCLUSIONS: Chromosome abnormality is the main causes of early miscarriage, and
      aneuploidies are the most common type of chromosomal abnormalities. Application
      of SNP array and karyotyping in early miscarriage can provide more genetic
      information about miscarriage, providing risk assessment to guide the next
      pregnancy.

PMID- 29034763
TI  - Pronuclear pattern does not predict morphokinetics behavior in human embryos.
AB  - The purpose was to investigate the correlation between pronuclei (PN) morphology
      and morphokinetic behaviors of derived embryos with time lapse monitoring (TLM)
      in assisted reproduction setting. Over time, PN morphology from PN appearance
      (PNA) to PN fading (PNF), PNF according to size, contact, number and position of
      nuclear precursor bodies (NPBs) within each PN and morphokinetics variables,
      including absolute time points, relative timing parameters, cleavage patterns and
      arrest rate, were evaluated using TLM. There were insignificant relationship
      between morphokinetics variables including tBP2, tPNA, tPNF, t2, t3, t4, t5, t6,
      t7, t8, S1, CC2, S2 and Z scoring according Z1 to Z4 (p > .05). Also, an
      insignificant relationship was noticed between uneven blastomeres, reverse
      cleavage embryos and Z scoring (p > .05). However, there were significant
      correlations between the rates of direct and arbitrary cleavage as well as
      arrested embryos and Z scores. Combined PN morphology and embryo kinetic
      evaluation were suggested in assisted reproduction programs.

PMID- 29034764
TI  - Indeterminate biliary strictures: a simplified approach.
AB  - INTRODUCTION: Pre-operative evaluation of biliary strictures remains challenging.
      The dilemma that exists is how to balance the risk of failing to detect
      malignancy and the potential morbidity caused by unnecessary surgery in patients
      with benign etiologies. With emerging novel diagnostic modalities, this study
      aims to assess the efficacy of diagnostic techniques and facilitate a clinical
      approach to indeterminate biliary strictures. Areas covered: Conventional imaging
      modalities are crucial in identifying the location of a stricture and are helpful
      for choosing further diagnostic modalities. Utilization of endoscopic techniques,
      including endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic
      ultrasound (EUS), is key in establishing a diagnosis. The emergence of novel
      diagnostic modalities, such as fluorescence in-situ hybridization (FISH), peroral
      cholangioscopy (POC), intraductal endoscopic ultrasound (IDUS) and confocal laser
      endomicroscopy (CLE), enhance the diagnostic yield in the evaluation of
      indeterminate biliary strictures. Expert commentary: More reliable and validated
      visual criteria for differentiating malignancy from benign biliary conditions,
      utilizing advanced imaging modalities such as POC and CLE, need to be
      established. It is of significance to further evaluate these novel diagnostic
      modalities through ongoing trials and to develop a diagnostic algorithm that
      reconciles cost-effectiveness with diagnostic accuracy.

PMID- 29034765
TI  - Assessment of maternal cerebral blood flow velocity by transcranial Doppler
      ultrasound before delivery and in the early postpartum period.
AB  - OBJECTIVE: This prospective observational study aimed to identify the effects of
      labor on cerebral hemodynamics by measuring the middle cerebral artery (MCA)
      blood flow velocity by transcranial Doppler ultrasound (TCD), and the related
      factors just before delivery and within the 24 h after delivery. METHODS: The
      study included 35 healthy pregnant women with a gestational age of >37 weeks who
      were in labor and a control group including healthy, age-matched, nonpregnant
      women (n = 24). Demographic characteristics and significant clinical information
      of pregnant women were recorded. The MCA blood flow velocity was assessed by TCD
      just before and within 24 h after delivery. The parameters assessed by TCD were
      mean cerebral blood flow velocity (MCBFV), peak systolic velocity (PSV),
      pulsatility index (PI), resistance index (RI), and systolic/diastolic ratio.
      RESULTS: There was no significant difference between the pregnant and nonpregnant
      women regarding age (27 +/- 5 years versus 28 +/- 7 years; p = .751). The MCBFV,
      PSV, PI, and RI showed a significant increase within the 24 h after delivery as
      compared with those before delivery. Comparison of the pregnant women with the
      control group in terms of the values of all parameters related to the MCA blood
      flow velocity revealed that the values that were significantly low before
      delivery reached to the level of the control group after delivery Conclusion: The
      findings of this study demonstrated that the blood flow velocity of the MCA
      decreased during the late pregnancy period and increased in the early postpartum
      period to the level similar to that of the nonpregnant group.

PMID- 29034766
TI  - Saddle seat reduces musculoskeletal discomfort in microsurgery surgeons.
AB  - BACKGROUND: Microsurgery is a surgical procedure requiring a high degree of
      precision and is commonly facilitated through the use of an intraoperative
      microscope. When operating the microscope system, the long-term posture leads to
      musculoskeletal disorders in surgeons, and seats are commonly employed to
      diminish these problems. The present study was conducted to evaluate
      musculoskeletal discomfort during work with a saddle seat in comparison with
      conventional seats for microscopic work. METHODS: Two types of seats, a saddle
      and a conventional one, were evaluated for 73 microsurgical surgeons in terms of
      musculoskeletal discomfort. Corlett and Bishop's body part discomfort scale was
      used to assess musculoskeletal discomfort before and after working with the
      seats. RESULTS: The highest amount of discomfort that microsurgical surgeons
      acquire in the workplace was focused on their neck, shoulders, arms and back.
      During work with a saddle seat, a significant reduction was found for discomfort
      values in the neck, shoulder, arm, back, elbow and forearm, as well as the whole
      body (p < 0.05). CONCLUSION: This study showed that the use of saddle seats
      provides a more appropriate physical posture at work, and can decrease
      musculoskeletal discomfort in different parts of the body of microsurgical
      surgeons.

PMID- 29034767
TI  - In Search of a Converging Cellular Mechanism in Nanotoxicology and Nanomedicine
      in the Treatment of Cancer.
AB  - Multiple applications of nanomaterials have raised concern with regard to their
      toxicity. With increasing research into nanomaterial safety, mechanisms involved
      in the toxic effects of nanomaterials have begun to emerge. The importance of
      nanomaterial-induced lysosomal membrane permeabilization through overloading or
      direct damage of the lysosomal compartment, resulting in the blockade of
      autophagosome-lysosome fusion and autophagy dysfunction, as well as inflammasome
      activation were cited as emerging mechanisms of nanomaterial toxicity. It has
      recently been proposed that these very mechanisms leading to nanomaterial
      toxicity may be utilized in nanotherapeutics. This review discusses these
      nanomaterial-induced mechanisms in detail and how it has been exploited in cancer
      research. This review also addresses certain considerations that need to be kept
      in mind when using nanomaterials in therapeutics.

PMID- 29034768
TI  - Effects on Cancellous Bone in the Metaphysis.
AB  - Cancellous bone has high metabolic activity compared to many other bone
      compartments and can be affected not only by changes in physeal activity but also
      by perturbations in homeostasis caused by changes in physiology or on-target
      pharmacology. Examples of several types of resulting morphologic findings were
      presented; if known, the pathways causing morphologic changes were discussed.

PMID- 29034769
TI  - Skeletal Muscle Toolbox.
AB  - Evaluation of skeletal muscle frequently combines morphologic and morphometric
      techniques. As is the case with many organ systems, skeletal muscle has limited
      responses to insult or injury. Over the past several years, crucial interactions
      between skeletal muscle, bone, and the nervous system have been described. The
      aim of this lecture was to give attendees the necessary background information in
      basic skeletal muscle morphology, important species differences, introduction to
      skeletal muscle biomarkers, approaches to morphologic and morphometric
      evaluation, and examples of background findings and typical responses of skeletal
      muscle to insult or injury.

PMID- 29034770
TI  - Association with polymorphic marmoset cytochrome P450 2C19 of in vivo hepatic
      clearances of chirally separated R-omeprazole and S-warfarin using individual
      marmoset physiologically based pharmacokinetic models.
AB  - 1. Simulated clearances of R-warfarin and efavirenz were recently reported for
      individual cynomolgus monkeys genotyped for cytochrome P450 2C19 and 2C9,
      respectively. To expand and verify this modeling procedure, simulations of R/S
      omeprazole and R/S-warfarin clearances after oral administrations in individual
      marmosets were performed using individual simplified physiologically based
      pharmacokinetic (PBPK) modeling consisting of gut, liver and central
      compartments. 2. Pharmacokinetics of R/S-omeprazole were chirally determined
      using the previously reported plasma microsamples in this study. The areas under
      the plasma concentration/time curves (AUC) of R-omeprazole and S-warfarin, but
      not S-omeprazole and R-warfarin, after oral administrations in the P450 2C19
      homozygous mutant group were significantly higher than those in the wild-type
      group. These modeled hepatic intrinsic clearances were also significantly
      associated with the marmoset P450 2C19 genotypes. Other parameter values, e.g.
      absorption rate constants or systemic circulation volumes, were not likely
      determining factors. 3. The reported individual AUC values measured in 4-6
      marmosets after oral R-omeprazole and S-warfarin administrations were
      significantly correlated with the AUC values predicted using the PBPK models
      after virtual administrations. 4. This study indicates that clearances of R
      omeprazole, S-warfarin and related medicines associated with polymorphic P450
      2C19 in individual marmosets can be simulated using simplified individual PBPK
      models.

PMID- 29034771
TI  - Genome-wide analysis of Epstein-Barr virus identifies variants and genes
      associated with gastric carcinoma and population structure.
AB  - Epstein-Barr virus is a ubiquitous virus and is associated with several human
      malignances, including the significant subset of gastric carcinoma, Epstein-Barr
      virus-associated gastric carcinoma. Some Epstein-Barr virus-associated diseases
      are uniquely prevalent in populations with different geographic origins. However,
      the features of the disease and geographically associated Epstein-Barr virus
      genetic variation as well as the roles that the variation plays in carcinogenesis
      and evolution remain unclear. Therefore, in this study, we sequenced 95
      geographically distinct Epstein-Barr virus isolates from Epstein-Barr virus
      associated gastric carcinoma biopsies and saliva of healthy donors to detect
      variants and genes associated with gastric carcinoma and population structure
      from a genome-wide spectrum. We demonstrated that Epstein-Barr virus revealed the
      population structure between North China and South China. In addition, we
      observed population stratification between Epstein-Barr virus strains from
      gastric carcinoma and healthy controls, indicating that certain Epstein-Barr
      virus subtypes are associated with different gastric carcinoma risks. We
      identified that the BRLF1, BBRF3, and BBLF2/BBLF3 genes had significant
      associations with gastric carcinoma. LMP1 and BNLF2a genes were strongly
      geographically associated genes in Epstein-Barr virus. Our study provides
      insights into the genetic basis of oncogenic Epstein-Barr virus for gastric
      carcinoma, and the genetic variants associated with gastric carcinoma can serve
      as biomarkers for oncogenic Epstein-Barr virus.

PMID- 29034772
TI  - Opa-interacting protein 5 modulates docetaxel-induced cell death via regulation
      of mitophagy in gastric cancer.
AB  - Damage to mitochondria induces mitophagy, a cellular process that is gaining
      interest for its therapeutic relevance to a variety of human diseases. However,
      the mechanism underlying mitochondrial depolarization and clearance in mitophagy
      remains poorly understood. We previously reported that mitochondria-induced cell
      death was caused by knockdown of Neisseria gonorrhoeae opacity-associated
      interacting protein 5 in gastric cancer. In this study, we show that Neisseria
      gonorrhoeae opacity-associated-interacting protein 5 loss and gain of function
      modulates mitophagy induced by treatment with docetaxel, a chemotherapy drug for
      gastric cancer. The activation of mitophagy by Neisseria gonorrhoeae opacity
      associated-interacting protein 5 overexpression promoted cell survival,
      preventing docetaxel-induced mitochondrial clearance. Conversely, short
      interfering RNA-mediated knockdown of Neisseria gonorrhoeae opacity-associated
      interacting protein 5 accelerated docetaxel-induced apoptosis while increasing
      mitochondrial depolarization, reactive oxygen species, and endoplasmic reticulum
      stress and decreasing adenosine triphosphate production. We also found that the
      mitochondrial outer membrane proteins mitofusin 2 and phosphatase and tensin
      homolog-induced putative kinase 1 colocalized with Neisseria gonorrhoeae opacity
      associated-interacting protein 5 in mitochondria and that mitofusin 2 knockdown
      altered Neisseria gonorrhoeae opacity-associated-interacting protein 5
      expression. These findings indicate that Neisseria gonorrhoeae opacity-associated
      interacting protein 5 modulates docetaxel-induced mitophagic cell death and
      therefore suggest that this protein comprises a potential therapeutic target for
      gastric cancer treatment.

PMID- 29034773
TI  - Substrate-dependent effects of molecular-targeted anticancer agents on activity
      of organic anion transporting polypeptide 1B1.
AB  - 1. Organic anion-transporting polypeptide 1B1 (OATP1B1) plays an important role
      in the hepatic uptake of a broad range of substrate drugs. In vitro experiments
      show that molecular-targeted agents do not always have similar effects on OATP1B1
      activity. 2. The purpose of this study was to clarify whether the effects of
      molecular-targeted agents on OATP1B1 are substrate-dependent. We used OATP1B1
      transfected cells to compare the effects of molecular-targeted agents on OATP1B1
      mediated uptake of fluorescein (FL), 2',7'-dichlorofluorescein (DCF),
      atorvastatin, SN-38 and valsartan. 3. Cabozantinib, cediranib, neratinib,
      pazopanib, regorafenib, sorafenib and tivantinib did not affect or only slightly
      affected OATP1B1-mediated substrate uptake. Nilotinib and lenvatinib moderately
      and strongly inhibited OATP1B1-mediated substrate uptake, respectively. In
      contrast, afatinib stimulated OATP1B1-mediated uptake of FL and SN-38, ceritinib
      stimulated that of valsartan, and nintedanib stimulated that of FL and valsartan.
      In addition, the effects of afatinib, ceritinib and nintedanib on OATP1B1
      activity differed markedly depending on the type of substrate. Afatinib,
      ceritinib and nintedanib had a substrate-dependent effect on OATP1B1 activity. 4.
      We conclude that the evaluation of OATP1B1 activity using only a single probe
      substrate for some molecular-targeted agents may lead to a faulty understanding
      of their mechanisms of drug interactions.

PMID- 29034774
TI  - Mechanical enhancement and in vitro biocompatibility of nanofibrous collagen
      chitosan scaffolds for tissue engineering.
AB  - The collagen-chitosan complex with a three-dimensional nanofiber structure was
      fabricated to mimic native ECM for tissue repair and biomedical applications.
      Though the three-dimensional hierarchical fibrous structures of collagen-chitosan
      composites could provide more adequate stimulus to facilitate cell adhesion,
      migrate and proliferation, and thus have the potential as tissue engineering
      scaffolding, there are still limitations in their applications due to the
      insufficient mechanical properties of natural materials. Because poly (vinyl
      alcohol) (PVA) and thermoplastic polyurethane (TPU) as biocompatible synthetic
      polymers can offer excellent mechanical properties, they were introduced into the
      collagen-chitosan composites to fabricate the mixed collagen/chitosan/PVA fibers
      and a sandwich structure (collagen/chitosan-TPU-collagen/chitosan) of nanofiber
      in order to enhance the mechanical properties of the nanofibrous collagen
      chitosan scaffold. The results showed that the tensile behavior of materials was
      enhanced to different degrees with the difference of collagen content in the
      fibers. Besides the Young's modulus had no obvious changes, both the break
      strength and the break elongation of materials were heightened after reinforced
      by PVA. For the collagen-chitosan nanofiber reinforced by TPU, both the break
      strength and the Young's modulus of materials were heightened in different
      degrees with the variety of collagen content in the fibers despite the decrease
      of the break elongation of materials to some extent. In vitro cell test
      demonstrated that the materials could provide adequate environment for cell
      adhesion and proliferation. All these indicated that the reinforced collagen
      chitosan nanofiber could be as potential scaffold for tissue engineering
      according to the different mechanical requirements in clinic.

PMID- 29034775
TI  - Risk factors of early recurrence after curative hepatectomy in hepatocellular
      carcinoma.
AB  - Early recurrence is common after curative hepatectomy for hepatocellular
      carcinoma and is associated with poor prognosis. This study aimed to identify
      risk factors of early recurrence after curative hepatectomy in hepatocellular
      carcinoma. Overall, 63 patients who underwent curative hepatectomy for
      hepatocellular carcinoma were enrolled. Patients were divided into the early
      recurrence group, who developed recurrence within 12 months after hepatectomy (n
      = 10), and the non-early recurrence group (n = 53). Clinicopathological factors
      of early recurrence were retrospectively analyzed. Among the 63 patients, 10
      (15.9%) patients experienced early recurrence. Univariate analysis showed tumor
      necrosis (p = 0.012), level of PIVKA-II (prothrombin induced by vitamin K absence
      or antagonist-II; p = 0.002), and microvascular invasion (p = 0.029) to be
      associated with early recurrence. By multivariate analysis, there were
      significant differences in high PIVKA-II (p < 0.001) and tumor necrosis (p =
      0.012) in patients with early recurrence. The optimal cutoff values of PIVKA-II
      and tumor necrosis were 46 mAU/mL and 3% of total tumor volume, respectively.
      Patients with a high preoperative PIVKA-II level and extent of tumor necrosis,
      which are independent risk factors for early recurrence, should be actively
      treated and monitored closely after hepatectomy.

PMID- 29034776
TI  - External Versus Two Different Internal Foci of Attention in Long-Distance
      Throwing.
AB  - The present study examined the influence of attentional focus on performance
      during a long-distance throwing task. Twelve participants executed three maximum
      effort, long-distance baseball throwing attempts in three focus conditions:
      internal focus on wrist flexion (wrist internal focus), internal focus on the
      separation between pelvis and upper torso orientations (torso internal focus),
      and external focus on the ball path (external focus). Compared with the external
      focus and torso internal focus conditions, performance was poorer in the wrist
      internal focus condition. Performances were not different in the torso internal
      and external focus conditions. In addition, attentional focus affected the
      release angle of the ball but not its initial velocity. Our results reveal that
      the body part targeted for internal focus of attention and the forcefulness of
      the motor activity can be as important to motor performance as whether the
      attention is internal or external.

PMID- 29034777
TI  - Effects of matrix metalloproteinase inhibitor doxycycline and CD147 antagonist
      peptide-9 on gallbladder carcinoma cell lines.
AB  - Gallbladder carcinoma is the most common and aggressive malignancy of the biliary
      tree and highly expresses CD147, which is closely related to disease prognosis in
      a variety of human cancers. Doxycycline exhibited anti-tumor properties in many
      cancer cells. CD147 antagonist peptide-9 is a polypeptide and can specifically
      bind to CD147. The effect of these two drugs on gallbladder cancer cells has not
      been studied. The aim of this study is to investigate the effect of doxycycline
      and antagonist peptide-9 on gallbladder carcinoma cells and the possible
      mechanism of inhibition on cancer cell of doxycycline. To investigate the effects
      of doxycycline and antagonist peptide-9 on gallbladder carcinoma cells (GBC-SD
      and SGC-996), cell proliferation, CD147 expression, and early-stage apoptosis
      rate were measured after treated with doxycycline. Matrix metalloproteinase-2 and
      matrix metalloproteinase-9 activities were measured after treated with different
      concentrations of doxycycline, antagonist peptide-9, and their combination. The
      results demonstrated that doxycycline inhibited cell proliferation, reduced CD147
      expression level, and induced an early-stage apoptosis response in GBC-SD and SGC
      996 cells. The matrix metalloproteinase-2 and matrix metalloproteinase-9
      activities were inhibited by antagonist peptide-9 and doxycycline, and the
      inhibitory effects were enhanced by combined drugs in gallbladder carcinoma cell
      lines. Taken together, doxycycline showed inhibitory effects on gallbladder
      carcinoma cell lines and reduced the expression of CD147, and this may be the
      mechanism by which doxycycline inhibits cancer cells. This study provides new
      information and tries to implement the design of adjuvant therapy method for
      gallbladder carcinoma.

PMID- 29034781
TI  - Point-of-Care Testing in Community Pharmacies: Keys to Success From Pennsylvania
      Pharmacists.
AB  - BACKGROUND: Clinical Laboratory Improvement Amendments (CLIA)-waived tests allow
      for quick, accurate, and noninvasive laboratory testing. Community pharmacists
      utilize CLIA-waived tests to provide clinical services such as point-of-care
      (POC) testing to help manage chronic disease and acute illness. OBJECTIVE: To
      identify key themes in the successful delivery of POC testing services by
      community pharmacists in Pennsylvania. RESULTS: An initial search identified 51
      Pennsylvania pharmacies with a CLIA waiver. Of these, five independent pharmacies
      met inclusion criteria, three of which completed interviews. The remaining 38
      chain pharmacies were represented by three interviews. In total, five key themes
      were identified as essential to POC testing services: (1) utilize state resources
      and professional connections to navigate federal and state regulations, (2)
      establish relationships with physician partners (3) offer tests that are
      meaningful to patients and their physicians, (4) evaluate financial impact,
      workflow adaptations, and marketing approaches when implementing POC testing
      services, and (5) focus on individualized attention and convenience of community
      pharmacy-based POC testing to improve patient satisfaction. CONCLUSION:
      Successful POC testing services in community pharmacy practice rely on utilizing
      resources, partnering with known physicians, selecting meaningful tests for
      patients, and analyzing finances, workflow, and marketing to provide
      individualized attention and convenient care.

PMID- 29034780
TI  - Mortality in endovascular and open abdominal aneurysm repair - trends in Germany.
AB  - BACKGROUND: We analysed trends in mortality of endovascular (EVAR) and open
      aortic repair (OAR) in patients hospitalized for abdominal aortic aneurysms (AAA)
      in Germany from 2005 to 2015. PATIENTS AND METHODS: We used national statistics
      published by the Federal Statistical Office in Germany to calculate mortality
      rate of patients hospitalized with ruptured (rAAA, n = 2,448 in 2005, n = 2,180
      in 2015) and non-ruptured (iAAA, n = 11,626 in 2005, n = 14,205 in 2015) AAA.
      RESULTS: Considering only those who were treated with EVAR or OAR, treatment
      rates of iAAA with EVAR increased to 78.2 % in males and 72.6 % in females in
      2015 and treatment rates of rAAA to 36.9 % and 40.7 %, respectively. In cases
      with iAAA, death rates associated with EVAR decreased in males from 2.1 to 1.1 %
      (p = 0.0005) in the period from 2005 to 2015 but not in females (1.8 % in 2005
      and 2.3 % in 2015, p = 0.8511). Similar trends are seen in cases with rAAA (males
      30.1 % and 24 %, p = 0.1034, females 36.4 to 37.3 %, p = 0.8511). Death rates
      associated with OAR increased in males from 4.7 % in 2005 to 5.7 % in 2015 (p =
      0.0103) and tended to increase in females from 6.8 to 8.2 % (p = 0.1476). In
      cases of rAAA, there were no changes. EVAR treatment rates increased in cases
      with iAAA in both genders with age, as well as in males with rAAA, but not in
      females. OAR associated death rates increased with age in rAAA (from around 30 %
      in the sixth/seventh decade of life to almost 80 % in cases with patients over
      the age of 90) and in iAAA (from 1.1 to 20 %). CONCLUSIONS: The general increase
      in EVAR procedures in males and females hospitalized for rAAA and iAAA went along
      with a decrease in in-hospital mortality in males treated with EVAR for iAAA only
      and an increasing mortality in males treated with OAR for iAAA.

PMID- 29034782
TI  - The Comparative Epidemiology of Pediatric Severe Sepsis.
AB  - OBJECTIVE: To determine whether the coding strategies used to identify severe
      sepsis in administrative data sets could identify cases with comparable case mix,
      hospitalization characteristics, and outcomes as a cohort of children diagnosed
      with severe sepsis using strict clinical criteria. METHODS: We performed a
      retrospective cohort study using data from 2005 to 2011 from the New York and
      Florida State Inpatient Databases, available from the US Healthcare Cost and
      Utilization Project. We compared 4 coding strategies: the single International
      Classification of Diseases, Ninth Revision, Clinical Modification ( ICD-9-CM)
      codes for (1) severe sepsis or (2) septic shock, and the algorithms developed by
      (3) Angus et al or (4) Martin et al, which use a combination of ICD-9-CM codes
      for infection and organ dysfunction. We compared the cases identified by each
      strategy with each other and with children enrolled in the REsearching severe
      Sepsis and Organ dysfunction in children: a gLobal perspectiVE (RESOLVE) trial.
      RESULTS: The Angus criteria was 9 times larger (n = 23 995) than the smallest
      cohort, identified by the "septic shock" code (n = 2 601). Cases identified by
      the Angus and Martin strategies had low mortality rates, while the cases
      identified by the "severe sepsis" and "septic shock" codes had much higher
      mortality at all time points (eg, 28-day mortality of 4.4% and 7.4% vs 15.4% and
      16.0%, respectively). Mortality in the "severe sepsis" and "septic shock" code
      cohorts was similar to that presented in the RESOLVE trial. CONCLUSIONS: The ICD
      9-CM codes for "severe sepsis" and "septic shock" identify smaller but higher
      acuity cohorts of patients that more closely resemble the children enrolled in
      the largest clinical trial of pediatric severe sepsis to date.

PMID- 29034783
TI  - Cerebral and Limb Tissue Oxygenation During Peripheral Venoarterial
      Extracorporeal Life Support.
AB  - Femoral access in extracorporeal life support (ECLS) has been associated with
      regional variations in arterial oxygen saturation, potentially predisposing the
      patient to ischemic tissue damage. Current monitoring techniques, however, are
      limited to intermittent bedside evaluation of capillary refill among other
      factors. The aim of this study was to assess whether cerebral and limb regional
      tissue oxygen saturation (rSO2) values reflect changes in various patient-related
      parameters during venoarterial ECLS (VA-ECLS). This retrospective observational
      study included adults assisted by femorofemoral VA-ECLS. Bifrontal cerebral and
      bilateral limb tissue oximetry was performed for the entire duration of support.
      Hemodynamic data were analyzed parallel to cerebral and limb rSO2. A total of 23
      patients were included with a median ECLS duration of 5 [1-20] days. Cardiac
      arrhythmias were observed in 12 patients, which was associated with a decreased
      mean rSO2 from 61%+/-11% to 51%+/-10% during atrial fibrillation and 67%+/-9% to
      58%+/-10% during ventricular fibrillation ( P<0.001 for both). A presumably
      sudden increase in cardiac output due to myocardial recovery (n=8) resulted in a
      significant decrease in mean cerebral rSO2 from 73%+/-7% to 54%+/-6% and from
      69%+/-9% to 53%+/-8% for the left and right cerebral hemisphere, respectively (
      P=0.012 for both hemispheres). Also, right radial artery partial gas pressure for
      oxygen decreased from 15.6+/-2.8 to 8.3+/-1.9 kPa ( P=0.028). No differences were
      found in cerebral desaturation episodes between patients with and without
      neurologic complications. In six patients, limb rSO2 increased from on average
      29.3+/-2.7 to 64.0+/-5.1 following insertion of a distal cannula in the femoral
      artery ( P=0.027). Likewise, restoration of flow in a clotted distal cannula
      inserted in the femoral artery was necessary in four cases and resulted in
      increased limb rSO2 from 31.3+/-0.8 to 79.5+/-9.0; P=0.068. Non-invasive tissue
      oximetry adequately reflects events influencing cerebral and limb perfusion and
      can aid in monitoring tissue perfusion in patients assisted by ECLS.

PMID- 29034784
TI  - Religious affiliation at time of death - Global estimates and projections.
AB  - AIMS: Religious affiliation influences societal practices regarding death and
      dying, including palliative care, religiously acceptable health service
      procedures, funeral rites and beliefs about an afterlife. We aimed to estimate
      and project religious affiliation at the time of death globally, as this
      information has been lacking. METHODS: We compiled data on demographic
      information and religious affiliation from more than 2500 surveys, registers and
      censuses covering 198 nations/territories. We present estimates of religious
      affiliation at the time of death as of 2010, projections up to and including
      2060, taking into account trends in mortality, religious conversion,
      intergenerational transmission of religion, differential fertility, and gross
      migration flows, by age and sex. RESULTS: We find that Christianity continues to
      be the most common religion at death, although its share will fall from 37% to
      31% of global deaths between 2010 and 2060. The share of individuals identifying
      as Muslim at the time of death increases from 21% to 24%. The share of
      religiously unaffiliated will peak at 17% in 2035 followed by a slight decline
      thereafter. In specific regions, such as Europe, the unaffiliated share will
      continue to rises from 14% to 21% throughout the period. CONCLUSIONS: Religious
      affiliation at the time of death is changing globally, with distinct regional
      patterns. This could affect spatial variation in healthcare and social customs
      relating to death and dying.

PMID- 29034786
TI  - Classifying head, face and oral pain.

PMID- 29034787
TI  - Role of adipocytokines in the pathophysiology of migraine: A cross-sectional
      study.

PMID- 29034785
TI  - Treatment history and antimicrobial susceptibility results for Mannheimia
      haemolytica, Pasteurella multocida, and Histophilus somni isolates from bovine
      respiratory disease cases submitted to the Iowa State University Veterinary
      Diagnostic Laboratory from 2013 to 2015.
AB  - Bovine respiratory disease is the most costly disease facing the cattle industry.
      Increasing resistance to antimicrobial treatment has been presented as a
      significant contributing factor, often through summarized susceptibility testing
      data. We assessed the relationship between previous antimicrobial treatment and
      antimicrobial susceptibility results from isolates of Mannheimia haemolytica,
      Pasteurella multocida, and Histophilus somni cultured from bovine respiratory
      cases submitted to the Iowa State University Veterinary Diagnostic Laboratory
      from 2013 to 2015. Antimicrobial susceptibility data from 1,251 bacterial
      isolates were included for analysis. More bacterial isolates from cattle that
      received antimicrobial treatment showed resistance compared to isolates from
      untreated cattle, and the percentage of resistant isolates increased as the
      number of antimicrobial treatments increased. Resistance to enrofloxacin,
      spectinomycin, tilmicosin, and tulathromycin was present in >75% of M.
      haemolytica isolates from cattle that had received 3 or more antimicrobial
      treatments; resistance to each of those 4 antimicrobials was present in <=10% of
      M. haemolytica isolates from untreated cattle. Similar but less dramatic trends
      were apparent for isolates of P. multocida and H. somni. The percentage of multi
      drug resistant bacterial isolates also increased with the number of treatments.
      Results of our study suggest that previous antimicrobial treatment may have a
      profound effect on antimicrobial susceptibility testing. Summarized
      susceptibility results from diagnostic laboratories should not be used to make
      generalized statements regarding trends in antimicrobial resistance without
      providing context regarding antimicrobial treatment history.

PMID- 29034788
TI  - Treatment of acute migraine attacks in children with analgesics on the World
      Health Organization Essential Medicines List: A systematic review and GRADE
      evidence synthesis.
AB  - Background The World Health Organization Essential Medicines List (WHO EML)
      contains two analgesics for treatment of acute migraine attacks in children,
      ibuprofen and paracetamol. Methods The Embase, CDSR, CENTRAL, DARE and MEDLINE
      databases were searched up to 18 April 2017. We analyzed randomized controlled
      trials (RCTs) and systematic reviews (SRs) that investigate the efficacy and
      safety of ibuprofen or paracetamol for treatment of acute migraine attacks in
      children. We conducted meta-analysis and assessments of evidence with GRADE,
      Cochrane risk of bias tool, and AMSTAR. Results Three RCTs (201 children) and 10
      SRs on ibuprofen and/or paracetamol for acute migraine attacks in children were
      included. Meta-analysis indicated that ibuprofen was superior to placebo for pain
      free at 2 h or pain relief at 2 h, without difference in adverse events. There
      were no differences between paracetamol and placebo, or ibuprofen and
      paracetamol. Ten SRs that analyzed various therapies for migraine in children
      were published between 2004 and 2016, with discordant conclusions. Conclusion
      Limited data from poor quality RCTs indicate that ibuprofen and paracetamol might
      be effective analgesics for treating migraine attacks in children. Inclusion of
      ibuprofen and paracetamol as antimigraine medicines for children in the WHO EML
      is supported by indirect evidence from studies in adults.

PMID- 29034789
TI  - A midterm report card for pulmonary embolism response teams.

PMID- 29034791
TI  - Point-of-care testing in the pharmacy: how is the field evolving?

PMID- 29034790
TI  - Minimal toxicity after proton beam therapy for prostate and pelvic nodal
      irradiation: results from the proton collaborative group REG001-09 trial.
AB  - BACKGROUND: Proton beam therapy (PBT) reduces normal organ dose compared to
      intensity modulated radiation therapy (IMXT) for prostate cancer patients who
      receive pelvic radiation therapy. It is not known whether this dosimetric
      advantage results in less gastrointestinal (GI) and genitourinary (GU) toxicity
      than would be expected from IMXT. MATERIAL AND METHODS: We evaluated treatment
      parameters and toxicity outcomes for non-metastatic prostate cancer patients who
      received pelvic radiation therapy and enrolled on the PCG REG001-09 trial.
      Patients who received X-ray therapy and/or brachytherapy were excluded. Of 3210
      total enrolled prostate cancer patients, 85 received prostate and pelvic
      radiation therapy exclusively with PBT. Most had clinically and radiographically
      negative lymph nodes although 6 had pelvic nodal disease and one also had para
      aortic involvement. Pelvic radiation therapy was delivered using either 2 fields
      (opposed laterals) or 3 fields (opposed laterals and a posterior beam). Median
      pelvic dose was 46.9 GyE (range 39.7-56) in 25 fractions (range 24-30). Median
      boost dose to the prostate +/- seminal vesicles was 30 GyE (range 20-41.4) in 16
      fractions (range 10-24). RESULTS: Median follow-up was 14.5 months (range 2.8
      49.2). Acute grade 1, 2, and 3 GI toxicity rates were 16.4, 2.4, 0%,
      respectively. Acute grade 1, 2, and 3 GU toxicity rates were 60, 34.1, 0%,
      respectively. CONCLUSIONS: Prostate cancer patients who receive pelvic radiation
      therapy using PBT experience significantly less acute GI toxicity than is
      expected using IMXT. Further investigation is warranted to confirm whether this
      favorable acute GI toxicity profile is related to small bowel sparing from PBT.

PMID- 29034792
TI  - Medical resource utilization and costs for total hip arthroplasty: benchmarking
      an anterior approach technique in the Medicare population.
AB  - AIMS: The anterior approach (AA) for total hip arthroplasty (THA) is associated
      with more rapid recovery when compared to traditional approaches. The purpose of
      this study was to benchmark healthcare resource utilization and costs for
      patients with THA via AA relative to matched patients. MATERIALS AND METHODS:
      This study queried Medicare claims data (2012-2014) to identify patients who
      received THA via an AA from experienced surgeons, and matched these patients to a
      control cohort (all THA approaches). Direct and propensity-score matching were
      employed to maximize similarity between patients and hospitals in the two
      cohorts. Hospital length of stay (LOS), the proportion of patients discharged to
      home or home health, and post-acute claim payments during the 90-day episode were
      assessed. Generalized estimating equations were applied to control for imbalances
      between the cohorts and clustering of outcomes within hospitals. RESULTS: A total
      of 1,794 patients were included after patient matching. Patients who received AA
      had significantly lower mean hospital LOS vs patients in the control group (2.06
      +/- 1.36 vs 2.98 +/- 1.58 days, p < .0001). The adjusted proportion of patients
      discharged to home was nearly 20 percentage points higher in the AA cohort vs the
      control cohort (87.3% vs 68.7%, p < .0001). Post-acute claim payments for AA
      patients were nearly 50% lower than those for control patients ($4,139 vs $7,465,
      p < .0001). CONCLUSION: AA patients had significantly lower post-acute care
      resource use when compared to control patients. Further research is warranted to
      evaluate the cost effectiveness of AA among surgeons of varying experience
      levels.

PMID- 29034794
TI  - Transmissions.

PMID- 29034796
TI  - No funeral bells: Public reason in a 'post-truth' age.
AB  - The label 'post-truth' signals for many a troubling turn away from principles of
      enlightened government. The word 'post', moreover, implies a past when things
      were radically different and whose loss should be universally mourned. In this
      paper, we argue that this framing of 'post-truth' is flawed because it is
      ahistorical and ignores the co-production of knowledge and norms in political
      contexts. Debates about public facts are necessarily debates about social
      meanings, rooted in realities that are subjectively experienced as all
      encompassing and complete, even when they are partial and contingent. Facts used
      in policy are normative in four ways: They are embedded in prior choices of which
      experiential realities matter, produced through processes that reflect
      institutionalized public values, arbiters of which issues are open to democratic
      contestation and deliberation, and vehicles through which polities imagine their
      collective futures. To restore truth to its rightful place in democracy,
      governments should be held accountable for explaining who generated public facts,
      in response to which sets of concerns, and with what opportunities for
      deliberation and closure.

PMID- 29034793
TI  - Patient's Utilization of Primary Care: A Profile of Clinical and Administrative
      Reasons for Visits in Israel.
AB  - BACKGROUND: Data on patients' utilization of health services in primary care is
      relevant to planning healthcare. Data may be collected by numerous methods, but
      obtaining a true picture of content of care has practical difficulties.
      OBJECTIVES: To describe patient's reasons for visits to primary care physicians
      (PCPs) as presented by the patient; and to examine the effect of patient-, doctor
      and clinic-related variables on the reasons for the visit. METHODS: Visits to
      PCPs were observed by peer doctors during 2014, at primary care clinics in
      Israel. Data were collected on characteristics of physicians, patients, clinics,
      type of visit, and reasons for visit. RESULTS: Eleven physicians from 7 clinics
      participated in the study. Data were gathered from 327 visits. Patients visited
      for a wide variety of reasons. The most common acute complaints were upper
      respiratory symptoms, gastrointestinal, skin symptoms, and back and neck
      problems. The most common chronic complaints were hypertension and diabetes.
      Patients presented with administrative requests in 36% of visits; 15% were for
      solely administrative issues. A total of 26.6% of visits included requests for
      blood tests or discussion of tests. Patients initiated preventive medicine issues
      in 5% of visits. Visits for chronic problems were directly correlated with
      patient age and the extent of acquaintance with the physician. Gender-associated
      differences were also found: women were more likely to visit for a new medical
      problem than men, while men were more likely to visit for known or chronic
      problems. CONCLUSIONS: Patients visit their PCP for a wide variety of reasons,
      often during the same visit. Patients refer for administrative requests in about
      a third of visits. They initiate preventive care infrequently (1 out of 20
      visits). To further characterize patient utilization of primary care, a broader
      study needs to be performed.

PMID- 29034797
TI  - Corrigendum.

PMID- 29034798
TI  - Intramuscular Electrical Stimulation for Muscle Activation of the Tibialis
      Anterior After Surgical Repair: A Case Report.
AB  - Background Loss of voluntary activation of musculature can result in muscle
      weakness. External neuromuscular stimulation can be utilized to improve voluntary
      activation but is often poorly tolerated because of pain associated with required
      stimulus level. Intramuscular electrical stimulation requires much lower voltage
      and may be better tolerated, and therefore more effective at restoring voluntary
      muscle activation. Case Description A 71-year-old man sustained a rupture of the
      distal attachment of the tibialis anterior tendon. Thirty-two weeks after
      surgical repair, there was no palpable or visible tension development in the
      muscle belly or tendon. Dorsiflexion was dependent on toe extensors. Electrical
      stimulation applied via a dry needling placement in the muscle belly was utilized
      to induce an isometric contraction. Outcomes Five sessions of intramuscular
      electrical stimulation were delivered. By day 4 (second visit), the patient was
      able to dorsiflex without prominent use of the extensor hallucis longus. By day 6
      (third visit), active-range-of-motion dorsiflexion with toes flexed increased 20
      degrees  (-10 degrees  to 10 degrees ). Eighteen days after the initial
      treatment, the patient walked without his previous high-step gait pattern, and
      the tibialis anterior muscle test improved to withstanding moderate resistance
      (manual muscle test score, 4/5). Discussion The rapid change in muscle function
      observed suggests that intramuscular electrical stimulation may facilitate
      voluntary muscle activation. Level of Evidence Therapy, level 5. J Orthop Sports
      Phys Ther 2017;47(12):965-969. Epub 15 Oct 2017. doi:10.2519/jospt.2017.7368.

PMID- 29034799
TI  - Measurement Properties of a Test Battery to Assess Postural Orientation During
      Functional Tasks in Patients Undergoing Anterior Cruciate Ligament Injury
      Rehabilitation.
AB  - Study Design Cross-sectional study. Background Visual rating of postural
      orientation during functional tasks may be a valuable tool to track
      rehabilitation progress following anterior cruciate ligament (ACL) injury. A
      valid test battery assessing postural orientation as a separate construct is
      lacking. Objectives To evaluate measurement properties of a test battery to
      assess postural orientation in patients with ACL injury. Methods The content
      validity of functional tasks was assessed by expert focus group discussions.
      Fifty-one patients (45% women) with ACL injury performed 9 functional tasks of
      varying difficulty. Interpretability, internal consistency, interrater
      reliability, and measurement error were assessed for segment-specific postural
      orientation errors (POEs), within-task POEs, and total POE score. Postural
      orientation errors were scored on video on an ordinal scale from 0 (no POEs) to 3
      (major POEs). Results Stair ascent, deep squat, and crossover hop for distance
      were excluded in focus group discussions. Postural orientation errors in some
      tasks were excluded due to floor effects. The mini-squat and drop jump were
      excluded due to poor internal consistency (alpha<=.184). Interrater reliability
      values for segment-specific POEs and within-task POEs yielded fair to almost
      perfect agreement (kappa = 0.429-0.875) and almost perfect agreement for total
      POE score (intraclass correlation coefficient = 0.842), without systematic
      differences between raters. The smallest detectable changes were 0.7 and 5 points
      for groups and individuals, respectively. Conclusion The final test battery
      (single-leg mini-squat, stair descent, forward lunge, single-leg hop for
      distance) of 4 POEs (foot pronation, medial knee-to-foot position, hip joint
      POEs, and trunk segment POEs) demonstrated good measurement properties in people
      with ACL injury. J Orthop Sports Phys Ther 2017;47(11):863-873.
      doi:10.2519/jospt.2017.7270.

PMID- 29034800
TI  - Hip and Knee Strengthening Is More Effective Than Knee Strengthening Alone for
      Reducing Pain and Improving Activity in Individuals With Patellofemoral Pain: A
      Systematic Review With Meta-analysis.
AB  - Study Design Systematic review with meta-analysis. Background The addition of hip
      strengthening to knee strengthening for persons with patellofemoral pain has the
      potential to optimize treatment effects. There is a need to systematically review
      and pool the current evidence in this area. Objective To examine the efficacy of
      hip strengthening, associated or not with knee strengthening, to increase
      strength, reduce pain, and improve activity in individuals with patellofemoral
      pain. Methods A systematic review of randomized and/or controlled trials was
      performed. Participants in the reviewed studies were individuals with
      patellofemoral pain, and the experimental intervention was hip and knee
      strengthening. Outcome data related to muscle strength, pain, and activity were
      extracted from the eligible trials and combined in a meta-analysis. Results The
      review included 14 trials involving 673 participants. Random-effects meta
      analyses revealed that hip and knee strengthening decreased pain (mean
      difference, -3.3; 95% confidence interval [CI]: -5.6, -1.1) and improved activity
      (standardized mean difference, 1.4; 95% CI: 0.03, 2.8) compared to no
      training/placebo. In addition, hip and knee strengthening was superior to knee
      strengthening alone for decreasing pain (mean difference, -1.5; 95% CI: -2.3, 
      0.8) and improving activity (standardized mean difference, 0.7; 95% CI: 0.2,
      1.3). Results were maintained beyond the intervention period. Meta-analyses
      showed no significant changes in strength for any of the interventions.
      Conclusion Hip and knee strengthening is effective and superior to knee
      strengthening alone for decreasing pain and improving activity in persons with
      patellofemoral pain; however, these outcomes were achieved without a concurrent
      change in strength. Level of Evidence Therapy, level 1a-. J Orthop Sports Phys
      Ther 2018;48(1):19-31. Epub 15 Oct 2017. doi:10.2519/jospt.2018.7365.

PMID- 29034801
TI  - Gluteus Minimus and Gluteus Medius Muscle Activity During Common Rehabilitation
      Exercises in Healthy Postmenopausal Women.
AB  - Study Design Controlled laboratory study, cross-sectional. Background The gluteus
      medius (GMed) and gluteus minimus (GMin) provide dynamic stability of the hip
      joint and pelvis. These muscles are susceptible to atrophy and injury in
      individuals during menopause, aging, and disease. Numerous studies have reported
      on the ability of exercises to elicit high levels of GMed activity; however, few
      studies have differentiated between the portions of the GMed, and none have
      examined the GMin. Objectives To quantify and rank the level of muscle activity
      of the 2 segments of the GMin (anterior and posterior fibers) and 3 segments of
      the GMed (anterior, middle, and posterior fibers) during 4 isometric and 3
      dynamic exercises in a group of healthy, postmenopausal women. Methods
      Intramuscular electrodes were inserted into each segment of the GMed and GMin in
      10 healthy, postmenopausal women. Participants completed 7 gluteal rehabilitation
      exercises, and average normalized muscle activity was used to rank the exercises
      from highest to lowest. Results The isometric standing hip hitch with
      contralateral hip swing was the highest-ranked exercise for all muscle segments
      except the anterior GMin, where it was ranked second. The highest-ranked dynamic
      exercise for all muscle segments was the dip test. Conclusion The hip hitch and
      its variations maximally activate the GMed and GMin muscle segments, and may be
      useful in hip muscle rehabilitation in postmenopausal women. J Orthop Sports Phys
      Ther 2017;47(12):914-922. Epub 15 Oct 2017. doi:10.2519/jospt.2017.7229.

PMID- 29034802
TI  - Unraveling the Mechanisms of Manual Therapy: Modeling an Approach.
AB  - Synopsis Manual therapy interventions are popular among individual health care
      providers and their patients; however, systematic reviews do not strongly support
      their effectiveness. Small treatment effect sizes of manual therapy interventions
      may result from a "one-size-fits-all" approach to treatment. Mechanistic-based
      treatment approaches to manual therapy offer an intriguing alternative for
      identifying patients likely to respond to manual therapy. However, the current
      lack of knowledge of the mechanisms through which manual therapy interventions
      inhibit pain limits such an approach. The nature of manual therapy interventions
      further confounds such an approach, as the related mechanisms are likely a
      complex interaction of factors related to the patient, the provider, and the
      environment in which the intervention occurs. Therefore, a model to guide both
      study design and the interpretation of findings is necessary. We have previously
      proposed a model suggesting that the mechanical force from a manual therapy
      intervention results in systemic neurophysiological responses leading to pain
      inhibition. In this clinical commentary, we provide a narrative appraisal of the
      model and recommendations to advance the study of manual therapy mechanisms. J
      Orthop Sports Phys Ther 2018;48(1):8-18. doi:10.2519/jospt.2018.7476.

PMID- 29034803
TI  - LncRNA HOXA11-AS promotes proliferation and invasion by targeting miR-124 in
      human non-small cell lung cancer cells.
AB  - Long non-coding RNAs have been implicated in human cancer but their mechanisms of
      action are mainly undocumented. In this study, we found that HOXA11-AS expression
      was upregulated in non-small cell lung cancer tissues and cell lines. High levels
      of HOXA11-AS expression were correlated with larger tumor size and lymph node
      metastasis. Functional analysis revealed that HOXA11-AS promotes non-small cell
      lung cancer cell proliferation and invasion. In particular, HOXA11-AS functions
      as a competing endogenous RNA to regulate transcriptional factor Sp1 expression
      via sponging miR-124. Collectively, our findings reveal an oncogenic role for
      HOXA11-AS in non-small cell lung cancer tumorigenesis.

PMID- 29034804
TI  - CIP2A expression predicts recurrences of tamoxifen-treated breast cancer.
AB  - CIP2A is emerging as an oncoprotein overexpressed commonly across many tumours
      and generally correlated with higher tumour grade and therapeutic resistance.
      CIP2A drives an oncogenic potential through inhibiting protein phosphatase 2A,
      stabilizing MYC, and promoting epithelial-to-mesenchymal transition, although
      further biological mechanisms for CIP2A are yet to be defined. CIP2A protein
      expression was studied by immunohistochemistry in oestrogen receptor-positive
      primary breast cancers (n = 250) obtained from the Leeds Tissue Bank. In total,
      51 cases presented with a relapse or metastasis during adjuvant treatment with
      tamoxifen and were regarded as tamoxifen resistant. CIP2A expression was scored
      separately for cytoplasmic, nuclear, or membranous staining, and scores were
      tested for statistically significant relationships with clinicopathological
      features. Membranous CIP2A was preferentially expressed in cases who experienced
      a recurrence during tamoxifen treatment thus predicting a worse overall survival
      (log rank = 8.357, p = 0.004) and disease-free survival (log rank = 21.766, p <
      0.001). Cox multivariate analysis indicates that it is an independent prognostic
      indicator for overall survival (hazard ratio = 4.310, p = 0.013) and disease-free
      survival (hazard ratio = 5.449, p = 0.002). In this study, we propose the
      assessment of membranous CIP2A expression as a potential novel prognostic and
      predictive indicator for tamoxifen resistance and recurrence within oestrogen
      receptor-positive breast cancer.

PMID- 29034805
TI  - In vitro investigation of the effect of matrix molecules on the behavior of colon
      cancer cells under the effect of geldanamycin derivative.
AB  - The chaperone-binding drug, 17-allylamino-17-demethoxygeldanamycin, has recently
      come into clinical use. It is a derivative of geldanamycin, an ansamycin
      benzoquinone antibiotic with anti-carcinogenic effect. Understanding the effect
      of this drug on the cancer cells and their niche is important for treatment. We
      applied 17-allylamino-17-demethoxygeldanamycin to colon cancer cell line (Colo
      205) on matrix molecules to investigate the relationship of apoptosis with
      terminal deoxynucleotidyl transferase dUTP nick end labeling immunocytochemistry
      and related gene expression. We used laminin and collagen I for matrix molecules
      and vascular endothelial growth factor for angiogenic structure. We also examined
      apoptosis-related signaling pathway including mitochondrial proteins, cytochrome
      c, Bcl-2, caspase-9, Apaf-1 expression using real-time polymerase chain reaction.
      There was clear effect of 17-allylamino-17-demethoxygeldanamycin that killed more
      cells on tissue culture plastic compared to matrix molecules. The IC50 value was
      0.58 ug/mL for tissue culture plastic compared with 0.64 ug/mL for laminin and
      0.75 ug/mL for collagen I. The analyses showed that more cells on matrix
      molecules underwent apoptosis compared to that on tissue culture plastic.
      Apoptosis-related gene expression was similar in which Bcl-2 expression decreased
      and proapoptotic gene expression of the cells on matrix molecules increased
      compared to that on tissue culture plastic. However, the application of 17
      allylamino-17-demethoxygeldanamycin was more effective for the cells on collagen
      I compared to the cells on laminin. There was also a decrease in angiogenesis as
      shown by the vascular endothelial growth factor staining. This was more
      pronounced by coating of the tissue culture plastic with matrix molecules. Our
      results supported the anti-cancer effect of 17-allylamino-17
      demethoxygeldanamycin, and this effect depended on matrix molecules. This effect
      occurs through apoptosis, and related genes were also altered. All these genes
      may serve for novel target under the effect of matrix substrate. However, correct
      interpretation of the results requires further studies.

PMID- 29034806
TI  - Exploring the East-West Divide in Prevalence of Affective Disorder: A Case for
      Cultural Differences in Coping With Negative Emotion.
AB  - Lifetime rates of clinical depression and anxiety in the West tend to be
      approximately 4 to 10 times greater than rates in Asia. In this review, we
      explore one possible reason for this cross-cultural difference, that Asian
      cultures think differently about emotion than do Western cultures and that these
      different systems of thought help explain why negative affect does not escalate
      into clinical disorder at the same rate. We review research from multiple
      disciplines-including cross-cultural psychology, social cognition, clinical
      psychology, and psychiatry-to make the case that the Eastern holistic principles
      of contradiction (each experience is associated with its opposite), change (the
      world exists in a state of constant flux), and context (the interconnectedness of
      all things) fundamentally shape people's experience of emotions in different
      cultures. We then review evidence for how these cultural differences influence
      how successfully people use common emotion regulation strategies such as
      rumination and suppression.

PMID- 29034810
TI  - Adult idiopathic cholestasis: a condition more common in the Canadian Inuit?
AB  - Despite extensive investigations, some patients have no identifiable cause for
      their cholestatic liver enzyme abnormalities. The aim of this study was to
      document the clinical, laboratory, radiologic and histologic features of adult
      patients with idiopathic cholestasis (AIC). A computerised database of referred
      patients to a tertiary care hospital outpatient department for assessment of
      hepatobiliary disorders between 2005 and 2015 was employed to identify and
      describe features associated with AIC. Of 6,560 patient referrals, sufficient
      documentation to warrant a diagnosis of AIC was present in 17 (0.26%) cases. Of
      the 17, a disproportionate number were Canadian Inuit (7/60, 12% Inuit referrals
      vs. 10/6,500, 0.16% non-Inuit referrals, p<0.0001). The median age of the 17
      subjects was 57 years and nine (53%) were female. Clinical and/or laboratory
      evidence of autoimmune disorders was present in six (35%) cases. Clinical
      features of hepatic decompensation, radiologic findings in keeping with cirrhosis
      and histologic confirmation of cirrhosis were present in 47%, 31% and 42% of
      individuals, respectively. There were no significant improvements in cholestatic
      liver enzymes and function tests in those treated with ursodiol and/or
      immunomodulants (n=7) compared to those left untreated (n=10). In conclusion, AIC
      is a rare condition diagnosed by exclusion. It appears to be more common in the
      Canadian Inuit population and those with autoimmune disorders. Advanced liver
      disease is a frequent finding at presentation. Intervention with ursodiol and/or
      immunomodulants does not appear to be of therapeutic value.

PMID- 29034811
TI  - Mental illness stigma among medical students and teachers.
AB  - BACKGROUND: Medical school curriculum contributes to future doctors' attitude
      formation towards people with mental illness. AIM: The purpose of this study was
      to compare stigmatizing attitudes between medical students and faculty, analyse
      stigmatizing attitudes among students from different years of study and identify
      factors predicting stigma. METHODS: A cross-sectional study with the use of
      scales measuring attitudes and social distance was designed. Online
      questionnaires were distributed to all students and teachers at a medical faculty
      in the Czech Republic. RESULTS: The response rate was 32.1% ( n = 308) among
      students and 26.7% ( n = 149) among teachers. Teachers had a greater prevalence
      of stigmatizing attitudes than students. Increased tolerant attitudes in students
      were detected after the fourth year, that is, following introduction to
      psychiatry. Preferred specialization in psychiatry and attending two psychiatry
      courses predicted more tolerant attitudes. Among both students and teachers, men
      possessed more stigmatizing attitudes towards people with mental illness. Age was
      an important predictor of stigmatizing attitudes among teachers. CONCLUSION:
      Educators should pay closer attention to the role of medical psychology and
      communication training implementation, which may be beneficial to improving
      skills and increasing medical students' self-esteem and feeling of competence
      throughout their psychiatry rotation.

PMID- 29034812
TI  - Symptom-reducing actions: a concept analysis in the context of chronic
      obstructive pulmonary disease.
AB  - Patients with Chronic Obstructive Pulmonary Disease (COPD) have multiple
      symptoms. Nursing care is based on six core competencies and one of them is
      person-centred care that includes the aspect of professional symptom relief. The
      aim was to clarify a meaning of the concept of Symptom-reducing actions in the
      context of COPD. Databases MEDLINE and CINAHL were searched between 1982 and
      February 2016 and 26 publications were found. Two dictionaries and three books
      were investigated. The method of Walker & Avant was followed. The use of the
      concept of Symptom-reducing actions may be categorized by the sub-concepts of
      supervision, information, and patient education. Exploration of defining
      attributes was symptom management, instructions, support, motivation,
      explanation, advice, teaching, and learning. Antecedent occurrences were related
      to factors that affect the patient's level of function such as physical
      performance and cognitive function. Symptom-reducing actions offer a way to
      support patients with COPD in self-management. Symptom-reducing actions can
      mediate facts in a purposeful process performed by the nurse to enable the
      patient to take control over and manage unpleasant symptoms by a person-centred,
      planned process. The nurse can achieve this via supervision, information, and
      patient education with an integrated emotional component. Evaluating the outcomes
      is needed.

PMID- 29034813
TI  - A review of medical terminology standards and structured reporting.
AB  - Much effort has been invested in standardizing medical terminology for
      representation of medical knowledge, storage in electronic medical records,
      retrieval, reuse for evidence-based decision making, and for efficient messaging
      between users. We only focus on those efforts related to the representation of
      clinical medical knowledge required for capturing diagnoses and findings from a
      wide range of general to specialty clinical perspectives (e.g., internists to
      pathologists). Standardized medical terminology and the usage of structured
      reporting have been shown to improve the usage of medical information in
      secondary activities, such as research, public health, and case studies. The
      impact of standardization and structured reporting is not limited to secondary
      activities; standardization has been shown to have a direct impact on patient
      healthcare.

PMID- 29034814
TI  - Entomophthoromycosis and mucormycosis as causes of pneumonia in Vietnamese
      potbellied pigs.
AB  - Two Vietnamese potbellied pigs ( Sus scrofa) had respiratory disease and, on
      autopsy, both pigs had large masses in the lungs and thoracic cavity.
      Microscopically, pulmonary and pleural masses contained large areas with hyphae
      surrounded by hypereosinophilic cellular debris rimmed by abundant eosinophils,
      lymphocytes, plasma cells, and histiocytes with occasional multinucleate giant
      cells. The hypereosinophilic debris usually formed tight cuffs, or "sleeves"
      around the hyphae, compatible with Splendore-Hoeppli-like material. The fungal
      organisms were determined by PCR to be Conidiobolus incongruus in one pig and
      Mucor circinelloides in the other. Entomophthoromycosis and mucormycosis should
      be included in the differential diagnoses for swine pneumonia, particularly when
      there is evidence of granulomatous pulmonary masses and pleural effusion with
      eosinophilic inflammation.

PMID- 29034815
TI  - Association of the vitamin D receptor FokI gene polymorphism with sex- and non
      sex-associated cancers: A meta-analysis.
AB  - Currently higher morbidity and mortality rates are observed in cancer diseases,
      especially sex-dependent cancers. A positive role of endogenous vitamin D
      concentration in cancer diseases has been reported in many publications.
      Furthermore, there has been observed a relationship between serum vitamin D and
      testosterone concentrations in an elderly Caucasian population carrying the
      vitamin D receptor FokI gene polymorphism. The aim of this study was to
      investigate whether the vitamin D receptor FokI polymorphism is associated with
      cancerogenesis in sex-dependent cancers. The MEDLINE and ResearchGate databases
      were used to search for articles up to January 2017, and 96 articles concerning
      the FokI polymorphism were chosen. Odds ratios with 95% confidence intervals were
      used to assess the strength of associations between polymorphisms of vitamin D
      receptor and cancer risk in the described populations. The fixed-effects model
      and the DerSimonian-Laird random-effects model (with weights based on the inverse
      variance) were used to calculate summary odds ratios, and both within- and
      between-study variation were considered. Generally, the F variant reduces the
      risk of cancer by 4% (odds ratio = 0.96, p value = 0.0057). This effect is
      particularly evident in female sex-associated cancers (odds ratio = 0.96, 95%
      confidence interval: 0.93-0.99, p value = 0.0259), but it is not observed in non
      sex-associated cancers. Polymorphism FokI is associated with breast and ovarian
      cancers.

PMID- 29034816
TI  - Clinical performance of LOCITM-based tumor marker assays for tumor markers CA 15
      3, CA 125, CEA, CA 19-9 and AFP in gynecological cancers.
AB  - Evidence is sparse regarding the clinical performance of luminescent oxygen
      channeling immunoassays-based tumor marker assays in gynecological cancer.
      Analyzing serum samples of 336 patients with DimensionTMVista1500, we
      investigated the diagnostic power of carbohydrate antigen 15-3, carbohydrate
      antigen 125, carcinoembryonic antigen, carbohydrate antigen 19-9, and alpha
      fetoprotein in patients suffering from different types of gynecological cancer
      and precancerous gynecological diseases and compared findings to appropriate
      control groups. The cohort comprised 177 female patients with gynecological
      cancers (73 breast, 22 cervical, 16 endometrial, 17 vulva, and 49 ovarian
      cancers), 26 patients with precancerous gynecological diseases (11 vulva, 4
      cervical, and 10 breast), 109 patients with benign gynecological diseases, and 24
      healthy controls. Discriminative power was assessed by areas under the curve in
      receiver operating characteristic curves, and sensitivities were determined at a
      fixed specificity of 95%. Levels of biomarkers in healthy controls were in the
      expected ranges and a discriminative power between gynecological cancers and
      healthy controls was observed for several tumor markers. Established tumor type
      associated markers were elevated in specific gynecological cancers and benign
      controls as well as within precancerous gynecological diseases and healthy
      control group. In ovarian cancer, carbohydrate antigen 125 and carbohydrate
      antigen 15-3 were significantly elevated compared to the respective benign
      diseases. Carbohydrate antigen 125 was the most conclusive marker (area under the
      curve = 0.86% and 77.6% sensitivity at 95% specificity). In breast cancer,
      carcinoembryonic antigen and carbohydrate antigen 15-3 were significantly higher
      than in the respective benign diseases. Carcinoembryonic antigen achieved the
      most conclusive area under the curve (0.65) with 31.5% sensitivity at 95%
      specificity. None of the investigated markers was found to be of value in
      discriminating benign and malignant cervical diseases. Carcinoembryonic antigen
      and alpha-fetoprotein distinguished precancerous breast and vulva diseases from
      healthy controls. These findings show that luminescent oxygen channeling
      immunoassays-based tumor marker assays provide reliable results in routine
      diagnostics.

PMID- 29034818
TI  - SCI Facts and Figures.

PMID- 29034817
TI  - Enhanced cytotoxic activity of effector T-cells against cholangiocarcinoma by
      dendritic cells pulsed with pooled mRNA.
AB  - Cholangiocarcinoma is a malignancy of bile duct epithelia with an increasing in
      incidence rate worldwide. Surgery is the only curative treatment, while adjuvant
      chemotherapy and radiotherapy render poor responses. Cell-based immunotherapy is
      a potential strategy for cholangiocarcinoma treatment. However, variation of
      tumor antigens in cholangiocarcinoma leads to the ineffectiveness of cell-based
      immunotherapy. In this study, we examined the activation of effector T-cells by
      dendritic cells pulsed with protein lysate or total RNA from cholangiocarcinoma
      cell lines for their cytolytic activity against cholangiocarcinoma. Broad
      spectrum antigen types with respect to RNA antigen sources were obtained from
      combination of three cholangiocarcinoma cell lines (KKU-213, KKU-100, and KKU
      055). Compared with protein lysate-pulsed dendritic cells, total RNA-pulsed
      dendritic cells induced anti-tumor effector T-cell response with higher killing
      ability to KKU-100 and KKU-213 cells compared with protein lysate-pulsed
      dendritic cells. Moreover, pooled messenger RNA from three cholangiocarcinoma
      cell lines significantly increased the specific killing capacity of activated
      lymphocytes against KKU-213 cells. These results suggest that activation of anti
      tumor effector T-cells against cholangiocarcinoma by RNA-pulsed dendritic cells
      is more effective than that by protein lysate-pulsed dendritic cells. In
      addition, pulsing dendritic cells with pooled messenger RNA from multiple cell
      lines enhanced the efficacy of a cellular immune response against
      cholangiocarcinoma.

PMID- 29034820
TI  - True North Strong and Free.

PMID- 29034819
TI  - Editors' Note.

PMID- 29034822
TI  - A Look at Traumatic Spinal Cord Injury in Canada: Rick Hansen Spinal Cord
      Registry (RHSCIR).

PMID- 29034823
TI  - Editorial Board Page.

PMID- 29034824
TI  - Welcome to the 7th National Spinal Cord Injury Conference! Celebrating our
      history.

PMID- 29034825
TI  - A tale of four practices.
AB  - Purpose The Patient-Centered Medical Home (PCMH) has become a dominant model of
      primary care re-design. This transformation presents a challenge to many care
      delivery organizations. The purpose of this paper is to describe attributes
      shaping successful and unsuccessful practice transformation within four medical
      practice groups. Design/methodology/approach As part of a larger study of 25
      practices transitioning into a PCMH, the current study focused on diabetes care
      and identified high- and low-improvement medical practices in terms of
      quantitative patient measures of glycosylated hemoglobin and qualitative
      assessments of practice performance. A subset of the top two high-improvement and
      bottom two low-improvement practices were identified as comparison groups. Semi
      structured interviews were conducted with diverse personnel at these practices to
      investigate their experiences with practice transformation and data were analyzed
      using analytic induction. Findings Results show a variety of key attributes
      facilitating more successful PCMH transformation, such as empanelment, shared
      goals and regular meetings, and a clear understanding of PCMH transformation
      purposes, goals, and benefits, providing care/case management services, and
      facilitating patient reminders. Several barriers also exist to successful
      transformation, such as low levels of resources to handle financial expense, lack
      of understanding PCMH transformation purposes, goals, and benefits, inadequate
      training and management of technology, and low team cohesion. Originality/value
      Few studies qualitatively compare and contrast high and low performing practices
      to illuminate the experience of practice transformation. These findings highlight
      the experience of organizational members and their challenges in practice
      transformation while providing quality diabetes care.

PMID- 29034826
TI  - Voice of the Clinician: the case of an Australian health system.
AB  - Purpose The Voice of the Clinician project commenced during an era when
      practitioner burnout, dissatisfaction, and turnover became an increasingly global
      health workforce concern. One key problem is clinical staff not being empowered
      to voice their concerns to decision-makers, as was found in this case study of an
      Australian public health organization. The following research question informed
      the present study: What is a better committee system for clinician engagement in
      decision-making processes? The paper aims to discuss this issue.
      Design/methodology/approach The Mid North Coast Local Health District in New
      South Wales aspired to improve engagement between frontline clinicians and
      decision-makers. Social network analysis methods and mathematical modeling were
      used in the discovery of how committees are connected to each other and
      subsequently to other committee members. Findings This effort uncovered a hidden
      organizational architecture of 323 committees of 926 members which overall cost
      84,729 person hours and AUD$2.923 million per annum. Furthermore, frontline
      clinicians were located far from centers of influence, just 37 percent of
      committees had terms of reference, and clinicians reported that meeting agendas
      were not being met. Practical implications In response to the findings, a
      technological platform was created so that the board of directors could visually
      see all the committees and the connections between them, thus creating ways to
      further improve communication, transparency of process, and - ultimately -
      clinician engagement. Originality/value The breakthrough idea is that all
      organizational meetings can be seen as a system of engagement and should be
      analyzed to determine and describe the points and pathways where clinician voice
      is blocked.

PMID- 29034827
TI  - Dealing with a changing work environment: hospital job type contingencies.
AB  - Purpose The purpose of this paper is twofold: first, to examine whether workers
      in various hospital job groups differ in their perceptions of the provision of
      managerial support, and of their up-to-date expertise (UDE), willingness to
      change (WTC) and employment opportunities (EO). Second, to examine whether and
      how the relationships between managerial support, workers' UDE, WTC and their EO
      are moderated by hospital job type. Design/methodology/approach Survey data were
      collected from 1,764 employees of three Dutch hospitals. ANOVAs and structural
      equation modeling were used to test the hypotheses. Findings The research
      findings indicate significant differences between the hospital job groups with
      regard to UDE, WTC and EO. No support was found for differences on managerial
      support nor for a moderating effect of hospital job type. The latter means that
      the relationships of managerial support with workers' UDE, WTC and EO are
      independent of job type. Originality/value Based on the findings, a
      classification system is constructed that shows how hospital workers' UDE, WTC
      and EO can be explained by the combination of the educational level required by a
      job and its degree of specialization.

PMID- 29034828
TI  - Professional expertise amongst speech-language therapists: "willing to share".
AB  - Purpose The current healthcare environment provides several challenges to the
      existing roles of healthcare professionals. The value of the professional expert
      is also under scrutiny. The purpose of this paper is to generate a construction
      of professional expertise amongst practitioners in the current healthcare
      environment. It used the speech-language therapy community in New Zealand (NZ) as
      an example. Design/methodology/approach Speech-language therapists currently
      practicing in NZ completed an online survey including qualitative and
      quantitative components. The range of experience and work settings of
      participants ( n=119) was representative of the workforce. Findings Participants
      clearly identified being "highly experienced" and "having in-depth knowledge" as
      essential elements of professional expertise. Thematic analysis generated two
      interconnected themes of a professional expert being a personal leader and
      teacher, and a highly experienced, knowledgeable and skilful practitioner.
      Additionally, practitioners needed to be seen to contribute to the community in
      order to be known as experts. Clinical practice was valued differently from
      research generation. Originality/value This study is novel in exploring a
      construction of professional expertise amongst practitioners in a current
      healthcare community. Within that community, experts could be viewed as highly
      effective practitioners that visibly contribute to the professional community.
      The study draws attention to the role of reputation and the impacts of being a
      clinical teacher or leader compared with pursuing a research role. This could be
      particularly relevant in the promotion of evidence-based practice.

PMID- 29034829
TI  - The impact of obesity on brain iron levels and alpha-synuclein expression is
      regionally dependent.
AB  - BACKGROUND: The importance of iron homeostasis is particularly apparent in the
      brain, where iron deficiency results in impaired cognition and iron accumulation
      is associated with neurodegenerative diseases. Obesity is linked to iron
      deficiency systemically, but the effects of obesity on brain iron and its
      associated consequences, including neurodegenerative processes remain unexplored.
      This preliminary study examined the effect of dietary-induced obesity on brain
      regional iron, alpha-synuclein expression, and F2-isoprostane (oxidative stress
      marker) concentrations in selected brain regions. OBJECTIVE: The objective of the
      study was to elucidate the vulnerability of selected brain regions (e.g.
      midbrain, hippocampus) to the possible process of neurodegeneration due to the
      altered iron content associated with obesity. METHODS: Twenty-one-day-old male
      C57BL/6J mice were fed with a high-fat diet (60% kcal from fat) or a control-fat
      diet (10% kcal from fat) for 20 weeks. Brain samples were collected and dissected
      into hippocampus, midbrain, striatum, and thalamus regions. Iron content,
      ferritin H (FtH) and alpha-synuclein protein and mRNA expressions, and F2
      isoprostane were measured in selected regions. RESULTS: The results indicated
      that obesity caused significant differences in iron levels in the midbrain and
      thalamus, but not in the hippocampus or striatum, compared to control mice.
      Furthermore, markers of neurodegeneration (alpha-synuclein mRNA expression and F2
      isoprostanes) were increased in the midbrain. DISCUSSION: These results support
      previous findings that brain iron metabolism responds to environmental stress in
      a regionally distinct manner and suggests that alterations in brain iron
      metabolism due to obesity may be relevant in neurodegeneration.

PMID- 29034830
TI  - Editorial: Fighting Against Kidney Injury.

PMID- 29034831
TI  - Graphene Oxide Based Metallic Nanoparticles and their Some Biological and
      Environmental Application.
AB  - BACKGROUND: Recently the decoration of graphene with metallic nanoparticles by a
      synchronized reduction of graphene oxide (GO) and synthesis of metallic
      nanoparticles has gained momentum. Metal-decorated carbon substrates, for
      example, carbon nanotubes and graphene oxide have been of interest to the
      scientific group all through the past three decades on account of different
      potential applications. The utilization of graphene oxide as the nano scale
      substrates for the formation of nanocomposites with metal oxides is a novel
      thought to acquire a hybrid which would show both the properties of GO as an
      interesting paper-shape material and the elements of single nanosized metal
      particles. METHODS: Graphene is a carbon allotrope of sp2 hybridized carbon atoms
      in a honeycomb lattice. It has attracted unique properties and potential
      applications. It has been synthesized and modified through various methods, and
      composites have been made with other nanomaterials, such as metals, metal oxides,
      and some complex oxides. RESULTS: Grapheme-metal oxide composites are gaining
      attention as a viable alternative to boost the efficiency of various catalytic,
      storage reactions in energy conversion, anticancer and drug delivery
      applications. Nevertheless, by combining the superior physical/chemical
      properties of GO themselves and the versatile nanomaterials that can decorate
      with GO, GO based materials have a bright future in the anticancer, drug
      delivery, energy, and environmental applications. CONCLUSION: This review article
      has described the recent publications in the development of Decoration of
      Graphene Oxide such as metals, metal oxides and their nanocomposites based
      materials. We anticipate this active field will continue growing rapidly, leading
      eventually to a variety of mature materials and devices that would benefit the
      society. Finally, the applications of composites are at their initial stages.
      They need to be studied systematically from both theoretical and experimental
      aspects.

PMID- 29034832
TI  - New Advances in Atrial Fibrillation Management: The Role of Apixaban.
AB  - BACKGROUND: Prevention of stroke is a pivotal intervention in the management of
      patients with atrial fibrillation (AF). Because of the difficulties of safely
      implementing Vitamin K Antagonists in all patients, there has been a growing
      interest in improving the pharmacological management of AF with newer
      antithrombotic agents. The new oral anticoagulants (NOACs) have been developed to
      overcome the limitations and improve the efficacy of the conventional oral
      anticoagulant drugs. Among the NOACs, apixaban - a very specific antagonist of
      activated factor Xa - has pharmacokinetic and pharmacodynamic properties that
      allow significant efficacy in AF management. OBJECTIVE: The aim of this review is
      to summarise the available data on the efficacy of apixaban in patients with AF,
      with a particular focus on the implications for its clinical management. RESULTS
      AND CONCLUSION: Clinical application of apixaban in subgroups of patients with AF
      is still under investigation and some contraindications should be taken into
      account. Despite these limitations, apixaban is an effective alternative to
      warfarin and aspirin for stroke prevention in AF, with encouraging evidence also
      in terms of adherence to treatment.

PMID- 29034833
TI  - Drug Therapy for Abdominal Aortic Aneurysms Utilizing Omega-3 Unsaturated Fatty
      Acids and Their Derivatives.
AB  - BACKGROUND: Abdominal aortic aneurysms (AAA) are life-threatening because of the
      potential for rupture, resulting in death. The current standard treatment for AAA
      is surgery, comprising laparotomic graft replacement and endovascular repair.
      However, because surgery carries the risk of major complications and re
      intervention, drug therapies are desirable because they may reduce the occurrence
      of enlargement and rupture. OBJECTIVE: Recent research shows that the progression
      of AAA is related to inflammatory reactions, especially those in the NF-kappaB
      pathway. Omega-3 polyunsaturated fatty acids (PUFA) show antiinflammatory
      effects. Some derivatives of omega-3 PUFA are known as specialized pro-resolving
      lipid mediators (SPM) such as resolvins. They play an important role in resolving
      inflammation. CONCLUSION: Omega-3 PUFA and SPM may show promised effects for drug
      treatment of AAA.

PMID- 29034834
TI  - Challenges and Advances in Gene Therapy Approaches for Neurodegenerative
      Disorders.
AB  - INTRODUCTION: The recent approval of Spinraza (nusinersen), an antisense
      oligonucleotide, by U.S. Food and Drug Administration to treat patients with
      spinal muscular atrophy, has reignited interests of researchers in designing and
      testing new gene therapy approaches to treat neurological disorders, in
      particular, to curb neurodegenerative diseases of the central nervous system
      which represent an ever-increasing public health burden to today's society.
      CONCLUSION: This review highlights several key factors to be taken into
      consideration to design successful preclinical and clinical gene therapy
      experiments with respect to the vehicle of delivery and the route of
      administration to CNS-specific targets, with an additional focus on antisense
      oligonucleotide therapy and recent clinical trial developments.

PMID- 29034835
TI  - Taste Masking Approaches for Medicines.
AB  - Undesirable taste is an important problem for patient compliance. Several oral
      pharmaceuticals and bulking agents have disagreeable and bitter-tasting
      components. The Bitter taste characteristics found in such systems have been
      eliminated or minimized by the development of numerous formulations with improved
      performance and acceptability especially in children and elderly patient. This
      review is mainly concerned with the bitter-masking techniques published in peer
      reviewed journals and will shed light on different methods of masking undesirable
      taste of the drugs, and their pharmaceutical applications. Hence, nearly no
      reference will be made to the techniques published as patent applications.

PMID- 29034836
TI  - Nanomedicine for Intranasal Delivery to Improve Brain Uptake.
AB  - Intranasal drug delivery system provides distinct advantage over conventional
      drug delivery system for a drug that is pharmacokenetically or biologically
      unstable. Major concern for the treatment of central nervous system diseases is,
      low concentration of therapeutically active molecule within brain as blood brain
      barrier is creating obstacle, where intranasal drug delivery provides direct
      transport of therapeutically active moiety into brain via olfactory or trigeminal
      pathway. Nasal mucosa provides distinct advantages like improved bioavailability,
      law dose and quick onset of action and high patient compliance, and the major
      disadvantage is residence time of drug and irreversible entrapment of drug. This
      article provides anatomical and physiological information about nasal route and
      various factors. Article discusses various types of nanoparticles used
      intranasally and moreover article also emphasizes patents, formulation under
      development and some.

PMID- 29034837
TI  - Dual-purpose Injectable Doxorubicin Conjugated Alginate Gel Containing
      Polycaprolactone Microparticles for Anti-Cancer and Anti-Inflammatory Therapy.
AB  - BACKGROUND: In situ gel formulations have been widely reported as a carrier for
      sustained release delivery systems due to certain advantages such as targeted
      drug delivery, minimal invasiveness and potent therapeutic activity. OBJECTIVE:
      Herein, in situ gel system for sustained release of doxorubicin and ibuprofen for
      anti-cancer and anti-inflammatory activity is reported. METHOD: Doxorubicin
      conjugated alginate (dox-alg) gel was prepared using EDC-NHS chemistry and loaded
      with ibuprofen encapsulated polycaprolactone (PCL) microparticles (dox-alg
      composite). PCL microparticles were prepared by a solvent evaporation method
      (size 50 - 100um). The gel was characterized using SEM, FTIR, XRD and TGA
      analysis. RESULTS: Dox-alg composite gel showed good syringeability and gel
      formation properties. Burst release was observed for both drugs within 24 h
      followed by sustained release till day 21. Doxorubicin released from composite
      showed considerable cytotoxic effect. Cell uptake was confirmed by confocal
      microscopy using MDA-MB-231 cells. Anti-inflammatory activity of ibuprofen
      released from composite gel was compared with the free drug. An injection of dox
      alg composite gel in the tissue would fill the void created after tumor removal
      surgery, prevent the resuscitation of remnant cancerous cells and reduce
      inflammation. CONCLUSION: Thus, the dox-alg composite gel could be a potential
      agent for the dual anti-cancer and anti-inflammatory therapy.

PMID- 29034839
TI  - Pharmacogenetics of Angiotensin-Converting Enzyme Inhibitors in Patients with
      Alzheimer's Disease Dementia.
AB  - BACKGROUND: While the angiotensin-converting enzyme degrades amyloid-beta,
      angiotensinconverting enzyme inhibitors (ACEis) may slow cognitive decline by way
      of cholinergic effects, by increasing brain substance P and boosting the activity
      of neprilysin, and by modulating glucose homeostasis and augmenting the secretion
      of adipokines to enhance insulin sensitivity in patients with Alzheimer's disease
      dementia (AD). We aimed to investigate whether ACE gene polymorphisms rs1800764
      and rs4291 are associated with cognitive and functional change in patients with
      AD, while also taking APOE haplotypes and anti-hypertensive treatment with ACEis
      into account for stratification. METHODS: Consecutive late-onset AD patients were
      screened with cognitive tests, while their caregivers were queried for functional
      and caregiver burden scores. Prospective pharmacogenetic correlations were
      estimated for one year, considering APOE and ACE genotypes and haplotypes, and
      treatment with ACEis. RESULTS: For 193 patients, minor allele frequencies were
      0.497 for rs1800764 - C (44.6% heterozygotes) and 0.345 for rs4291 - T (38.9%
      heterozygotes), both in Hardy-Weinberg equilibrium. Almost 94% of all patients
      used cholinesterase inhibitors, while 155 (80.3%) had arterial hypertension, and
      124 used ACEis. No functional impacts were found regarding any genotypes or
      pharmacological treatment. Either for carriers of ACE haplotypes that included
      rs1800764 - T and rs4291 - A, or for APOE4- carriers of rs1800764 - T or rs4291 -
      T, ACEis slowed cognitive decline independently of blood pressure variations.
      APOE4+ carriers were not responsive to treatment with ACEis. CONCLUSION: ACEis
      may slow cognitive decline for patients with AD, more remarkably for APOE4-
      carriers of specific ACE genotypes.

PMID- 29034838
TI  - Formulation, Optimization and Evaluation of Organogel for Topical Delivery of
      Acyclovir.
AB  - BACKGROUND: The conventional acyclovir topical therapy has a low efficacy, due to
      the lack of penetration of a sufficient amount of drug to the target site.
      OBJECTIVE: The aim of this work was to formulate and optimize organogel
      containing acyclovir to enhance the penetration and retention time of acyclovir
      in the basal epidermis, site of Herpes simplex virus infections. METHODS:
      Microemulsion based organogel containing acyclovir was developed using the
      combination of surfactants, polar and nonpolar solvents. To investigate the
      microemulsion and gelling region, titration was carried out and pseudoternary
      phase diagram was constructed. The formulation was optimized by using 3-factor, 3
      level, Box-Behnken design. Response surface plots were constructed for various
      response variables, viz. % drug permeation, viscosity and spreadability. The
      optimized formulation was searched utilizing overlay plots and desirability of
      the response. The optimized formulation was further characterized for microscopy,
      pH, ex-vivo permeation etc. Ex-vivo skin permeation showed first order drug
      diffusion through the skin and was found being stable upto 8 hrs. RESULTS: In
      case of developed organogel formulation, significantly higher amount of acyclovir
      was observed to be retained in the skin, as compared to retention observed with
      the conventional cream. CONCLUSION: The results show that the ACV organogel
      penetrates into the skin and form the reservoir that can slowly release the drug
      for a longer period and may control viral growth more effectively.

PMID- 29034840
TI  - Non-Anaesthetic Effects of Volatile Anaesthetics: A Short Trip on the Sea of
      Translational Medicine.
AB  - BACKGROUND: Volatile Anaesthetics (VA) are commonly used worldwide for induction
      and/or maintenance of general anaesthesia. They act in the central nervous system
      to reduce sensation and motor response during surgical and invasive diagnostic
      procedures. VAs also have some non-anaesthetic properties in the brain when
      administrated to patients at the extremes of age. Their biological impact on
      other organs should be taken into account during administration of anaesthesia.
      OBJECTIVE: In this review we summarize the recent knowledge on the non
      anaesthetic effects of inhaled halogenic ethers on cells and tissues. RESULTS AND
      CONCLUSION: Exposure to VAs may promote lasting neuro-behavioural deficits in the
      brains of developing children and deterioration in cognitive performance in
      elderly individuals. Preconditioning with VAs can prevent or minimise tissue
      ischaemia in the heart and brain. VAs act as an antiinflammatory in response to
      tissue damage during surgery and may attenuate both local and systemic
      inflammatory response. Further research is needed to elucidate a link between
      laboratory findings and their possible effects in humans. Because many questions
      remain unanswered in this field, translational medicine should be more focused on
      safety in anaesthesia for the improvement public health.

PMID- 29034821
TI  - Abstracts and Workshops 7th National Spinal Cord Injury Conference November 9 -
      11, 2017 Fallsview Casino Resort Niagara Falls, Ontario, Canada.

PMID- 29034841
TI  - PPAR-gamma and Wnt Regulate the Differentiation of MSCs into Adipocytes and
      Osteoblasts Respectively.
AB  - BACKGROUND: Under the transcriptional control of numerous factors and
      intracellular signals, mesenchymal stem cells (MSCs) can differentiate into
      various cell types, including adipocytes and osteoblasts. However, the precise
      cellular signaling factors that determine the cell fate of MSCs in bone marrow
      remain largely unknown. OBJECTIVE: In this review, we focus on the ties of PPAR
      gamma and Wnt signaling in MSC differentiation into adipocytes and osteoblasts.
      RESULTS: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is well
      established as a prime inducer of adipogenesis, while the Wnt pathway is regarded
      as the master moderator of osteogenesis. A theoretical inverse relationship
      exists between adipogenic and osteogenic lineage commitment and differentiation:
      the differentiation toward an osteoblast phenotype occurs at the expense of an
      adipocyte phenotype. CONCLUSION: It has been proposed that the balance between
      osteogenic and adipogeneic MSC differentiation is disrupted in diverse areas of
      human health. Therefore, understanding the ties between PPAR- gammaand Wnt
      signaling in MSC differentiation has significant implications in diverse areas of
      human health, from obesity to osteoporosis to regenerative medicine.

PMID- 29034843
TI  - Research Progress in Reversal of Tumor Multi-drug Resistance via Natural
      Products.
AB  - Multidrug resistance occurs when a tumor develops resistance to multiple
      chemotherapeutic drugs, which may include antitumor drugs with different chemical
      structures and mechanisms. Multidrug resistance limits the treatment effects of
      antitumor drugs, and is the main cause of chemotherapy failure. Multidrug
      resistance is caused by numerous factors including changes in ATP-binding
      cassette transporters, target proteins, detoxification, deoxyribonucleic acid
      repair, drug metabolic enzymes, and signal pathways of apoptosis. Clinical
      research indicates that natural products have great potential to treat tumors and
      reverse multidrug resistance. Natural products, which often have multiple
      targets, could play an important role in tumor treatment, have beneficial effects
      on tumor inhibition, improve symptoms, reduce radiotherapy and chemotherapy side
      effects, enhance immunity, and prolong survival. Because natural products often
      have few adverse reactions and less drug resistance, the antitumor activities of
      natural products have attracted extensive research. We aimed to review the basic
      research and clinical application of natural products in the reversal of
      multidrug resistance.

PMID- 29034844
TI  - MicroRNAs, Cancer and Diet: Facts and New Exciting Perspectives.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs able to regulate gene
      expression at multiple levels. They are detected in tissues, blood, and other
      body fluids with high stability and have a recognized role in maintaining of
      tissue homeostasis. Aberrant expression profile of miRNAs has been observed in
      several diseases, primarily cancer. As a consequence, the analysis of miRNA
      signature has recognized diagnostic and prognostic role in human diseases, and
      the development of miRNA-based therapies is currently under investigation.
      Recently, emerging but controversial data have revealed the possibility that diet
      derived miRNAs might be transferred from food in living organisms to regulate
      gene expression. Thus, exogenous dietderived miRNAs might substantially
      contribute to the pool of circulating miRNAs to preserve tissue homeostasis and
      health status in recipient's organisms, opening new perspectives for diet in
      heath and disease. OBJECTIVE: This brief review aims at summarizing data
      concerning the recognized role of miRNAs as biomarkers, drugs and therapeutic
      targets in cancer and the detection and the activity of diet-derived miRNAs in
      both physiological and pathological conditions. CONCLUSION: MiRNAs have emerged
      as crucial molecules in anticancer therapies and diet-derived miRNAs might
      contribute to the pool of circulating miRNAs to preserve, maintain or restore
      health.

PMID- 29034845
TI  - Predicting miRNA Association with Corresponding Target Genes and Single
      Nucleotide Polymorphisms in Altered Renal Pathophysiology.
AB  - BACKGROUND: Translational research on miRNAs develops reliable biomarkers for
      diagnosis and prognosis of renal diseases. Bioinformatic analyses and systems
      biology could drive the research for knowing new informative miRNA targets.
      OBJECTIVES: This study proposes an approach to identify miRNA specific
      significant target genes, and single nucleotide polymorphisms (SNPs) associated
      with renal pathophysiology. METHODS: miRNAs were selected after removing
      duplicity, on the basis of techniques used, and disease spectrum width score.
      Target genes were predicted from different databases like miRWalk, miRTarBase,
      and DIANA-TarBase. SNPs were prioritized on the basis of target score and
      conserved energy score available in MirSNP database. miRNAs were characterized as
      "specific", "strong", "likely", "unlikely", and "irrelevant" biomarkers. PCR-SSP
      based genotyping was carried out to access the molecular profiling of hsa-miR-192
      and TGF-beta1 followed by quantitative real time PCR to analyze expression level
      of TGF-beta1. The relative expression levels of mRNAs were analyzed by 2
      DeltaDeltaCt method. RESULTS: 170 renal associated miRNAs were found to be up
      regulated, down-regulated or differentially expressed. Noticeably hsa-miR-192-3p
      expression was reported in nine diseases. 117 genes were associated with basic
      kidney diseases and end stage renal disease (ESRD). Threshold > 80% for 93 target
      genes was observed from mirSVR. Mutant genotypes for hsa-miR-192 (OR=4.64, p
      value <= 0.0001) and its corresponding target gene TGF-beta1 (OR = 0.70, p-value
      = 0.0351) showed susceptible association with ESRD. More so, patients possessing
      mutant allele of TGF-beta1 showed elevated mRNA expression (Fold change = 9.83).
      CONCLUSION: Study proposed a new approach to identify specific miRNA biomarkers
      for particular diseases with corresponding target genes and SNPs and also
      highlighted the importance of hsa-miR-192 in renal diseases.

PMID- 29034846
TI  - Kocuria salina sp. nov., an actinobacterium isolated from the rhizosphere of the
      halophyte Arthrocnemum macrostachyum and emended description of Kocuria
      turfanensis.
AB  - A novel, non-motile coccoid, Gram-positive and non-endospore forming bacterium,
      designated Hv14bT, was isolated from the rhizosphere of the halophyte
      Arthrocnemum macrostachyum. It was observed to be catalase positive and oxidase
      negative and able to hydrolyse starch. MK-8(H2) was identified as the dominant
      menaquinone and the major cellular fatty acids were anteiso-C15 : 0 and iso-C15 :
      0. The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol and an
      unidentified glycolipid. The 16S rRNA genes showed the highest 16S rRNA sequence
      identity with K. polaris DSM 14382T, K. rosea DSM 20447T and K. turfanensis DSM
      22143T. Based on the phenotypic and molecular features and DNA-DNA hybridization
      data, it is concluded that strain Hv14bT is proposed to represent a novel species
      in the genus Kocuria, Kocuria salina sp. nov., with the type strain Hv14bT=DSM
      28714T=CECT 9229T.

PMID- 29034848
TI  - Characterization of thermotolerant phototrophic bacteria, Rhodoplanes tepidicaeni
      sp. nov. and Rhodoplanes azumiensis sp. nov., isolated from a geothermal spring.
AB  - Two strains of thermotolerant phototrophic alphaproteobacteria, designated
      strains TUT3542T and TUT3581T, were isolated from sediment mud and cyanobacterial
      mats in a geothermal spring in Japan, respectively, and taxonomically
      characterized. Both the strains were budding motile rods and were able to grow at
      45  degrees C. Phototrophically grown cells of strains TUT3542T and TUT3581T
      produced pink and brownish red cultures, respectively, and showed in vivo
      absorption maxima at 800, 858-859 and 892-895 nm in the near infrared region,
      indicating the presence of a core reaction centre and peripheral pigment
      complexes with bacteriochlorophyll a. The intracytoplasmic membrane system was of
      the lamellar type parallel to the cytoplasmic membrane. 16S rRNA gene sequence
      comparisons showed that strains TUT3542T and TUT3581T had the highest similarity
      level to Rhodoplanes oryazae NBRC 109406T (99.6 %) and Rhodoplaneselegans AS130T
      (99.3 %), respectively. Genomic DNA-DNA reassociation studies revealed that
      strains TUT3542T and TUT3581T had hybridization levels of less than 62 and 56 %
      to the type strains of all established species of the genus Rhodoplanes,
      respectively. The G+C contents of genomic DNA were 67.7 mol% for strain TUT3542T
      and 70.4 mol% for strain TUT3581T. Results of phenotypic studies showed that the
      two novel strains could be differentiated from any of the previously described
      Rhodoplanes species. Thus, the author proposes the names Rhodoplanes tepidicaeni
      sp. nov. for strain TUT3542T and Rhodoplanes azumiensis sp. nov. for strain
      TUT3581T. The type strain of Rhodoplanes tepidicaeni is TUT3542T (=KCTC
      15602T=NBRC 112815T) and the type strain of Rhodoplanes azumiensis is TUT3581T
      (=KCTC 15603T=NBRC 112816T).

PMID- 29034847
TI  - Aurantimonas aggregata sp. nov., isolated from deep-sea sediment.
AB  - A novel bacterium, designated R14M6T, was isolated from deep-sea sediment
      collected from the Ross Sea, Antarctica. Cells are Gram-stain-negative, aerobic,
      pale yellow, short-rod-shaped, polar-flagellated and aggregate-forming. Growth
      occurs at 4-36  degrees C, pH 6.0-8.3, and in 1-15 % (w/v) NaCl. Phylogenetic
      analysis based on 16S rRNA gene sequences showed that strain R14M6T clustered
      together with Aurantimonas endophytica EGI6500337T and fell within the genus
      Aurantimonas. The 16S rRNA gene sequence of strain R14M6T shared similarity with
      A. endophytica EGI6500337T (99.15 %), A. manganoxydans DSM 21871T (97.73 %), A.
      coralicida DSM 14790T (97.58 %) and 'A. litoralis' KCTC 12094 (97.51 %). The DNA
      DNA relatedness values between strain R14M6T and A. endophytica EGI6500337T, A.
      coralicida DSM 14790T, A. manganoxydans DSM 21871T and 'A. litoralis' KCTC 12094
      were 36.9+/-4.5, 27.6+/-2.8, 29.6+/-1.2 and 25.2+/-2.4 % respectively. The major
      fatty acid of strain R14M6T was C18 : 1omega7c. The major polar lipids were
      phosphatidylcholine, diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine and an unidentified aminolipid. Strain R14M6T contained
      Q-10 as the dominant isoprenoid quinone. The DNA G+C content of strain R14M6T was
      67.4 mol%. Based on the phylogenetic, physiological and chemotaxonomic analyses,
      strain R14M6T represents a novel species of the genus Aurantimonas, for which the
      name Aurantimonas aggregata sp. nov. is proposed. The type strain is R14M6T
      (=GDMCC 1.1202T=KCTC 52919T).

PMID- 29034849
TI  - Streptomyces amphotericinicus sp. nov., an amphotericin-producing actinomycete
      isolated from the head of an ant (Camponotus japonicus Mayr).
AB  - A novel actinomycete, designated strain 1H-SSA8T, was isolated from the head of
      an ant (Camponotus japonicus Mayr) and was found to produce amphotericin. A
      polyphasic approach was employed to determine the status of strain 1H-SSA8T.
      Morphological and chemotaxonomic characteristics were consistent with those of
      members of the genus Streptomyces. The menaquinones detected were MK-9(H6), MK
      9(H8) and MK-9(H4). The phospholipid profile consisted of diphosphatidylglycerol,
      phosphatidylmethylethanolamine, phosphatidylethanolamine and phosphatidylinositol
      mannoside. The major fatty acids were identified as iso-C16 : 0, C16 : 0, C15 : 0
      and anteiso-C15 : 0. Analysis of the 16S rRNA gene sequence showed that strain 1H
      SSA8T belongs to the genus Streptomyces with high sequence similarity to
      Streptomyces ramulosus NRRL B-2714T (99.2 %). Two tree-making algorithms based on
      16S rRNA gene sequences showed that the isolate formed a phyletic line with
      Streptomyces himastatinicus ATCC 53653T (98.7 %). The MLSA utilizing partial
      sequences of the housekeeping genes (atpD, gyrB, recA, rpoB and trpB) also
      supported the position. However, evolutionary distances were higher than the
      0.007 MLSA evolutionary distance threshold proposed for species-level
      relatedness. Moreover, the low level of DNA-DNA relatedness and phenotypic
      differences allowed the novel isolate to be differentiated from its most closely
      related strain S. ramulosus NRRL B-2714T and strain S. himastatinicus ATCC
      53653T. It is concluded that the organism can be classified as representing a
      novel species of the genus Streptomyces, for which the name Streptomyces
      amphotericinicus sp. nov. is proposed. The type strain is 1H-SSA8T (=CGMCC
      4.7350T=DSM 103128T).

PMID- 29034851
TI  - Nitrosopumilus maritimus gen. nov., sp. nov., Nitrosopumilus cobalaminigenes sp.
      nov., Nitrosopumilus oxyclinae sp. nov., and Nitrosopumilus ureiphilus sp. nov.,
      four marine ammonia-oxidizing archaea of the phylum Thaumarchaeota.
AB  - Four mesophilic, neutrophilic, and aerobic marine ammonia-oxidizing archaea,
      designated strains SCM1T, HCA1T, HCE1T and PS0T, were isolated from a tropical
      marine fish tank, dimly lit deep coastal waters, the lower euphotic zone of
      coastal waters, and near-surface sediment in the Puget Sound estuary,
      respectively. Cells are straight or slightly curved small rods, 0.15-0.26 um in
      diameter and 0.50-1.59 um in length. Motility was not observed, although strain
      PS0T possesses genes associated with archaeal flagella and chemotaxis, suggesting
      it may be motile under some conditions. Cell membranes consist of glycerol
      dibiphytanyl glycerol tetraether (GDGT) lipids, with crenarchaeol as the major
      component. Strain SCM1T displays a single surface layer (S-layer) with p6
      symmetry, distinct from the p3-S-layer reported for the soil ammonia-oxidizing
      archaeon Nitrososphaera viennensis EN76T. Respiratory quinones consist of fully
      saturated and monounsaturated menaquinones with 6 isoprenoid units in the side
      chain. Cells obtain energy from ammonia oxidation and use carbon dioxide as
      carbon source; addition of an alpha-keto acid (alpha-ketoglutaric acid) was
      necessary to sustain growth of strains HCA1T, HCE1T, and PS0T. Strain PS0T uses
      urea as a source of ammonia for energy production and growth. All strains
      synthesize vitamin B1 (thiamine), B2 (riboflavin), B6 (pyridoxine), and B12
      (cobalamin). Optimal growth occurs between 25 and 32  degrees C, between pH 6.8
      and 7.3, and between 25 and 37 0/00 salinity. All strains have a low mol% G+C
      content of 33.0-34.2. Strains are related by 98 % or greater 16S rRNA gene
      sequence identity, sharing ~85 % 16S rRNA gene sequence identity with
      Nitrososphaera viennensis EN76T. All four isolates are well separated by
      phenotypic and genotypic characteristics and are here assigned to distinct
      species within the genus Nitrosopumilus gen. nov. Isolates SCM1T (=ATCC TSD-97T
      =NCIMB 15022T), HCA1T (=ATCC TSD-96T), HCE1T (=ATCC TSD-98T), and PS0T (=ATCC TSD
      99T) are type strains of the species Nitrosopumilusmaritimus sp. nov.,
      Nitrosopumilus cobalaminigenes sp. nov., Nitrosopumilus oxyclinae sp. nov., and
      Nitrosopumilus ureiphilus sp. nov., respectively. In addition, we propose the
      family Nitrosopumilaceae fam. nov. and the order Nitrosopumilales ord. nov.
      within the class Nitrososphaeria.

PMID- 29034850
TI  - Pseudomonas aeruginosa variants obtained from veterinary clinical samples reveal
      a role for cyclic di-GMP in biofilm formation and colony morphology.
AB  - Overuse of antibiotics is contributing to an emerging antimicrobial resistance
      crisis. To better understand how bacteria adapt tolerance and resist antibiotic
      treatment, Pseudomonas aeruginosa isolates obtained from infection sites sampled
      from companion animals were collected and evaluated for phenotypic differences.
      Selected pairs of clonal isolates were obtained from individual infection samples
      and were assessed for antibiotic susceptibility, cyclic di-GMP levels, biofilm
      production, motility and genetic-relatedness. A total of 18 samples from equine,
      feline and canine origin were characterized. A sample from canine otitis media
      produced a phenotypically heterogeneous pair of P. aeruginosa isolates, 42121A
      and 42121B, which during growth on culture medium respectively exhibited hyper
      dye-binding small colony morphology and wild-type phenotypes. Antibiotic
      susceptibility to gentamicin and ciprofloxacin also differed between this pair of
      clonal isolates. Sequence analysis of gyrA, a gene known to be involved in
      ciprofloxacin resistance, indicated that 42121A and 42121B both contained
      mutations that confer ciprofloxacin resistance, but this did not explain the
      differences in ciprofloxacin resistance that were observed. Cyclic di-GMP levels
      also varied between this pair of isolates and were shown to contribute to the
      observed colony morphology variation and ability to form a biofilm. Our results
      demonstrate the role of cyclic di-GMP in generating the observed morphological
      phenotypes that are known to contribute to biofilm-mediated antibiotic tolerance.
      The generation of phenotypic diversity may go unnoticed during standard
      diagnostic evaluation, which potentially impacts the therapeutic strategy chosen
      to treat the corresponding infection and may contribute to the spread of
      antibiotic resistance.

PMID- 29034852
TI  - Comparison of direct-plating and broth-enrichment culture methods for detection
      of potential bacterial pathogens in respiratory secretions.
AB  - OBJECTIVE: We compared the recovery of potential respiratory bacterial pathogens
      and normal flora from nasopharyngeal specimens collected from children during
      health and at the onset of acute otitis media (AOM) by selective direct-plating
      and overnight broth-enrichment. METHODS: Overall, 3442 nasal wash (NW) samples
      collected from young children were analysed from a 10-year prospective study. NWs
      were cultured by (1) direct-plating to TSAII/5 % sheep blood agar and chocolate
      agar plates and (2) overnight broth-enrichment in BacT/ALERT SA-broth followed by
      plating. Standard microbiology techniques were applied to identify three dominant
      respiratory bacterial pathogens: Streptococcus pneumoniae (Spn), Haemophilus
      influenzae (Hflu) and Moraxella catarrhalis (Mcat) as well as two common nasal
      flora, Staphylococcus aureus (SA) and alpha-haemolytic Streptococci
      (AHS).Results/Key findings. Direct-plating of NW resulted in isolation of Spn
      from 37.8 %, Hflu from 13.6 % and Mcat from 33.2 % of samples. In comparison,
      overnight broth-enrichment isolated fewer Spn (30.1 %), Hflu (6.2 %) and Mcat
      (16.2 %) (P<0.001-0.0001). Broth-enrichment resulted in significant increased
      isolation of SA (6.0 %) and AHS (30.1 %) (P<0.0001). Competition between
      bacterial species in broth when both species were detected by direct-plating was
      assessed, and it was found that SA and AHS out-competed other species during
      broth-enrichment when samples were collected from healthy children but not during
      AOM. In middle ear fluids (MEF) at the onset of AOM, broth-enrichment resulted in
      higher recovery of Spn (+10.4 %, P<0.001), Hflu (+4.4 %, P=0.39) and Mcat (+13.5
      %, <0.001). CONCLUSION: Broth-enrichment significantly reduces the accurate
      detection of bacterial respiratory pathogens and increases identification of SA
      and AHS in NW. Broth-enrichment improves detection of bacterial respiratory
      pathogens in MEF samples.

PMID- 29034853
TI  - Floricoccus tropicus gen. nov., sp. nov. and Floricoccus penangensis sp. nov.
      isolated from fresh flowers of durian tree and hibiscus.
AB  - Three strains of Gram-staining-positive, coccus-shaped, lactic acid bacteria,
      designated as HibF3T, HibF2 and HibF5 were isolated from fresh flowers of
      hibiscus, and a fourth, DF1T, was isolated from fresh flowers of durian tree, in
      Penang, Malaysia. Taxonomic characterisation was performed by polyphasic
      analysis. Sequence similarities of the 16S rRNA gene and the housekeeping rpoA
      and pheS genes of these strains with their closely-related lactococcal and
      streptococcal relatives were 92-94, 78 and 81 %, respectively. The results of
      phylogenetic analysis indicated that strains DF1T, HibF2, HibF5 and HibF3T were
      clustered together but were clearly separated from species of the genera
      Streptococcus and Lactococcus, indicating that they represent members of a novel
      genus of the family Streptococcaceae. Calculation of average nucleotide identity
      (ANI) values between the genomes of DF1T and HibF3T yielded values of 92.50-92.93
      %. ANI values below the cut-off value and distinctive chemotaxonomic
      characteristics supported the hypothesis that these strains represented two novel
      species. Major cellular fatty acids in DF1T, HibF2 and HibF5 were C18 : 1omega7c
      and C16 : 0, while C12 : 0 and C14 : 0 were also dominant, in addition to C18 :
      1omega7c and C16 : 0, in HibF3T. A novel genus is proposed with the name
      Floricoccus gen. nov. which consists of two species, Floricoccus tropicus sp. nov
      as the type species, and Floricoccus penangensis sp. nov. The respective type
      strains are DF1T (=LMG 29833T=JCM 31733T) and HibF3T (=LMG 29831T=DSM 31735T).

PMID- 29034855
TI  - Bradyrhizobium namibiense sp. nov., a symbiotic nitrogen-fixing bacterium from
      root nodules of Lablab purpureus, hyacinth bean, in Namibia.
AB  - Four strains of symbiotic bacteria from root nodules of hyacinth bean (Lablab
      purpureus (L.) Sweet) from Namibia were previously identified as a novel group
      within the genus Bradyrhizobium. To confirm their taxonomic status, these strains
      were further characterized by taking a polyphasic approach. The type strain
      possessed 16S rRNA gene sequences identical to Bradyrhizobium paxllaeri LMTR 21T
      and Bradyrhizobiumicense LMTR 13T, the full-length sequences were identical to
      those retrieved from SAMN05230119 and SAMN05230120, respectively. However, the
      intergenic spacer sequences of the novel group showed identities of less than
      93.1 % to described Bradyrhizobium species and were placed in a well-supported
      separate lineage in the phylogenetic tree. Phylogenetic analyses of six
      concatenated housekeeping genes, recA, glnII, gyrB, dnaK, atpD and rpoB,
      corroborated that the novel strains belonged to a lineage distinct from named
      species of the genus Bradyrhizobium, with highest sequence identities to
      Bradyrhizobiumjicamae and B. paxllaeri (below 93 %). The species status was
      validated by results of DNA-DNA hybridization and average nucleotide identity
      values of genome sequences. The combination of phenotypic characteristics from
      several tests, including carbon source utilization and antibiotic resistance,
      could be used to differentiate representative strains from recognized species of
      the genus Bradyrhizobium. Phylogenetic analysis of nodC and nifH genes placed the
      novel strains in a group with B. paxllaeri and B.lablabi. Novel strain 5-10T
      induces effective nodules on Lablab purpureus, Vigna subterranea, Vigna
      unguiculata and Arachis hypogaea. Based on our results, we conclude that our
      strains represent a novel species for which the name Bradyrhizobium namibiense
      sp. nov. is proposed, with type strain 5-10T[LMG 28789, DSM 100300, NTCCM0017
      (Windhoek)].

PMID- 29034854
TI  - Whole genome transcriptomics reveals global effects including up-regulation of
      Francisella pathogenicity island gene expression during active stringent response
      in the highly virulent Francisella tularensis subsp. tularensis SCHU S4.
AB  - During conditions of nutrient limitation bacteria undergo a series of global gene
      expression changes to survive conditions of amino acid and fatty acid starvation.
      Rapid reallocation of cellular resources is brought about by gene expression
      changes coordinated by the signalling nucleotides' guanosine tetraphosphate or
      pentaphosphate, collectively termed (p)ppGpp and is known as the stringent
      response. The stringent response has been implicated in bacterial virulence, with
      elevated (p)ppGpp levels being associated with increased virulence gene
      expression. This has been observed in the highly pathogenic Francisella
      tularensis sub spp. tularensis SCHU S4, the causative agent of tularaemia. Here,
      we aimed to artificially induce the stringent response by culturing F. tularensis
      in the presence of the amino acid analogue l-serine hydroxamate. Serine
      hydroxamate competitively inhibits tRNAser aminoacylation, causing an
      accumulation of uncharged tRNA. The uncharged tRNA enters the A site on the
      translating bacterial ribosome and causes ribosome stalling, in turn stimulating
      the production of (p)ppGpp and activation of the stringent response. Using the
      essential virulence gene iglC, which is encoded on the Francisella pathogenicity
      island (FPI) as a marker of active stringent response, we optimized the culture
      conditions required for the investigation of virulence gene expression under
      conditions of nutrient limitation. We subsequently used whole genome RNA-seq to
      show how F. tularensis alters gene expression on a global scale during active
      stringent response. Key findings included up-regulation of genes involved in
      virulence, stress responses and metabolism, and down-regulation of genes involved
      in metabolite transport and cell division. F. tularensis is a highly virulent
      intracellular pathogen capable of causing debilitating or fatal disease at
      extremely low infectious doses. However, virulence mechanisms are still poorly
      understood. The stringent response is widely recognized as a diverse and complex
      bacterial stress response implicated in virulence. This work describes the global
      gene expression profile of F. tularensis SCHU S4 under active stringent response
      for the first time. Herein we provide evidence for an association of active
      stringent response with FPI virulence gene expression. Our results further the
      understanding of the molecular basis of virulence and regulation thereof in F.
      tularensis. These results also support research into genes involved in (p)ppGpp
      production and polyphosphate biosynthesis and their applicability as targets for
      novel antimicrobials.

PMID- 29034856
TI  - Franconibacter daqui sp. nov., a facultatively alkaliphilic species isolated from
      a Daqu sample.
AB  - A novel bacterium, designated strain DL503T, was isolated from a Daqu sample and
      its taxonomic position determined using a polyphasic taxonomy. Strain DL503T was
      a Gram-stain-negative, facultatively anaerobic, non-sporulating, motile and
      coccoid-rod-shaped bacterium. Optimum growth occurred at 20-45  degrees C, pH 5.0
      10.0 and 1.5 % (w/v) NaCl. Comparative analysis of the 16S rRNA gene sequence
      showed that the isolate belongs to the genus Franconibacter, showing highest
      levels of similarity with respect to Franconibacter pulveris JCM 16471T (98.94 %)
      and Franconibacter helveticus DSM 18396T (98.39 %). Cells contained the quinones
      Q-8 and MK-8, and the polar lipid profile consisted of a mixture of
      phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, three
      unidentified polar lipids and three unidentified amino lipids. The DNA G+C
      content was 53.3 mol% and the major fatty acids were C16 : 0, C17 : 0 cyclo,
      summed feature 3 (C16 : 1 omega7c and/or C16 : 1 omega6c), summed feature 4 (C17
      : 1 iso I and/or C17 : 1 anteiso B) and summed feature 8 (C18 : 1 omega7c and/or
      C18 : 1 omega6c). The DNA-DNA relatedness values between strain DL503T and its
      close relatives, including F. pulveris JCM 16471T and F. helveticus DSM 18396T,
      were 51.5+/-0.5 % and 45.2+/-1.1 %, respectively. Based on phylogenetic analysis,
      phenotypic and genotypic data, it is concluded that the isolate represents a
      novel species of the genus Franconibacter, for which the name Franconibacter
      daqui sp. nov. is proposed. The type strain is DL503T (=LMG 29914T=CGMCC
      1.15944T).

PMID- 29034858
TI  - Streptomyces kalpinensis sp. nov., an actinomycete isolated from a salt water
      beach.
AB  - A novel actinobacterium designated TRM 46509T was isolated from a salt water
      beach at Kalpin, Xinjiang, north-west China. The strain was aerobic and Gram
      stain-positive, with an optimum NaCl concentration for growth of 1 % (w/v). The
      isolate formed sparse aerial mycelium and produced spiral spores at the end of
      the aerial mycelium on Gauze's No. 1 medium. The isolate contained ll
      diaminopimelic acid as the diagnostic diamino acid and ribose as the major whole
      cell sugar. The polar lipids included diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol,
      phosphatidylinositol mannosides and an unidentified phospholipid. The predominant
      menaquinones were MK-9(H2), MK-9(H6) and MK-9(H8). The major fatty acids were
      C16:0, iso-C16 : 0, anteiso-C15 : 0, iso-C15 : 0 and iso-C14 : 0. The G+C content
      of the DNA was 69.3 mol%. Phylogenetic analysis showed that strain TRM 46509T
      shared 16S rRNA gene sequence similarity of 97.6 % with the closest described
      species Streptomyces tacrolimicus ATCC 55098T. On the basis of evidence from this
      polyphasic study, strain TRM 46509T should be designated as representing a novel
      species of the genus Streptomyces, for which the name Streptomyces kalpinensis
      sp. nov. is proposed. The type strain is TRM 46509T (=CCTCC AA 2015028T=KCTC
      39667T).

PMID- 29034859
TI  - Massilia neuiana sp. nov., isolated from wet soil.
AB  - A novel aerobic, Gram-stain-negative, rod-shaped, motile bacterium, strain
      PTW21T, was isolated from wet soil. 16S rRNA gene sequence phylogenetic analysis
      of strain PTW21T revealed an affiliation to the genus Massilia and it shared 98.5
      and 98.1 % similarity with Massilianiastensis 5516 S-1T and Massilia tieshanensis
      TS3T, respectively. Growth occurred at 10-45  degrees C, pH 4.5-12.5 and NaCl
      concentrations up to 2 % (w/v). The major fatty acids were summed feature 3 (C16
      : 1omega7c and/or iso-C15 : 0 2-OH) and C16 : 0. The predominant respiratory
      quinone was Q-8. The major polar lipids were diphosphatidylglycerol,
      phosphatidylethanolamine and phosphatidylglycerol. The DNA G+C content of strain
      PTW21T was 64.6 mol%. The results of DNA-DNA hybridization revealed that strain
      PTW21T showed 37.4 % relatedness with Massilia niastensis 5516 S-1T and 40.0 %
      with M. tieshanensis TS3T. Based on phenotypic, chemotaxonomic and phylogenetic
      differences, strain PTW21T (=CICC 24113T=BCRC 81061T) is proposed as the type
      strain of novel species of the genus Massilia with the names Massilia neuiana sp.
      nov.

PMID- 29034860
TI  - Comparison of two automated instruments for Epstein-Barr virus serology in a
      large adult hospital and implementation of an Epstein-Barr virus nuclear antigen
      based testing algorithm.
AB  - Serology remains the mainstay for diagnosis of Epstein-Barr virus (EBV)
      infection. This study compared two automated platforms (BioPlex 2200 and
      Architect i2000SR) to test three EBV serological markers: viral capsid antigen
      (VCA) immunoglobulins of class M (IgM), VCA immunoglobulins of class G (IgG) and
      EBV nuclear antigen-1 (EBNA-1) IgG. Using sera from 65 patients at various stages
      of EBV disease, BioPlex demonstrated near-perfect agreement for all EBV markers
      compared to a consensus reference. The agreement for Architect was near-perfect
      for VCA IgG and EBNA-1 IgG, and substantial for VCA IgM despite five equivocal
      results. Since the majority of testing in our hospital was from adults with EBNA
      1 IgG positive results, post-implementation analysis of an EBNA-based algorithm
      showed advantages over parallel testing of the three serologic markers. This
      small verification demonstrated that both automated systems for EBV serology had
      good performance for all EBV markers, and an EBNA-based testing algorithm is
      ideal for an adult hospital.

PMID- 29034857
TI  - Minimal standards for describing new species belonging to the families
      Campylobacteraceae and Helicobacteraceae: Campylobacter, Arcobacter, Helicobacter
      and Wolinella spp.
AB  - Ongoing changes in taxonomic methods, and in the rapid development of the
      taxonomic structure of species assigned to the Epsilonproteobacteria have lead
      the International Committee of Systematic Bacteriology Subcommittee on the
      Taxonomy of Campylobacter and Related Bacteria to discuss significant updates to
      previous minimal standards for describing new species of Campylobacteraceae and
      Helicobacteraceae. This paper is the result of these discussions and proposes
      minimum requirements for the description of new species belonging to the families
      Campylobacteraceae and Helicobacteraceae, thus including species in
      Campylobacter, Arcobacter, Helicobacter, and Wolinella. The core underlying
      principle remains the use of appropriate phenotypic and genotypic methods to
      characterise strains sufficiently so as to effectively and unambiguously
      determine their taxonomic position in these families, and provide adequate means
      by which the new taxon can be distinguished from extant species and subspecies.
      This polyphasic taxonomic approach demands the use of appropriate reference data
      for comparison to ensure the novelty of proposed new taxa, and the recommended
      study of at least five strains to enable species diversity to be assessed.
      Methodological approaches for phenotypic and genotypic (including whole-genome
      sequence comparisons) characterisation are recommended.

PMID- 29034861
TI  - Clostridium pabulibutyricum sp. nov., a butyric-acid-producing organism isolated
      from high-moisture grass silage.
AB  - A Gram-stain-variable, strictly anaerobic, rod-shaped, catalase-negative and
      endospore-forming bacterial strain, designated MJC39T, was isolated from grass
      silage preserved in Hokkaido, Japan. Growth occurred at 20-42  degrees C, pH 5.0
      7.0 and NaCl concentrations up to 2 % (w/v). The isolated strain MJC39T produced
      butyric acid in peptone yeast extract medium with glucose. The DNA G+C content of
      strain MJC39T was 34.4+/-0.2 mol%. The major cellular fatty acids (>10 %) were
      C14 : 0, C16 : 0 and summed feature 3 (including C16 : 1omega7c/C16 : 1omega6c).
      No respiratory quinones were detected. The polar lipids of strain MJC39T were
      phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, one
      unidentified lipid, one unidentified aminolipid, two unidentified glycolipids,
      one unidentified phospholipid, one unidentified aminoglycolipid and one
      unidentified phosphoaminoglycolipid. Phylogenetic analysis based on 16S rRNA gene
      sequences showed that strain MJC39T was a member of the genus Clostridium and is
      closely related to Clostridium tyrobutyricum JCM 11008T (95.8 % similarity) and
      Clostridium algifaecis MB9-7T (95.5 % similarity). Based on the genotypic,
      phenotypic and chemotaxonomic characteristics, strain MJC39T represents a novel
      species of the genus Clostridium, for which the name Clostridium pabulibutyricum
      sp. nov. is proposed. The type strain is MJC39T (=JCM 31506T=DSM 103944T).

PMID- 29034862
TI  - Ultrastructural and microbial analyses of cellulose degradation in leaf-cutter
      ant colonies.
AB  - Leaf-cutter ants (Atta and Acromyrmex) use fresh leaves to cultivate a
      mutualistic fungus (Leucoagaricus gongylophorus) for food in underground gardens.
      A new ant queen propagates the cultivar by taking a small fragment of fungus from
      her parent colony on her nuptial flight and uses it to begin her own colony.
      Recent research has shown that the ants' fungus gardens are colonized by
      symbiotic bacteria that perform important functions related to nitrogen fixation
      and have been implicated in contributing to plant biomass degradation. Here, we
      combine bacterial culturing in several media for counts and identification using
      the 16S rRNA gene with electron microscopy to investigate the process of
      cellulose degradation in the fungus garden and refuse dumps, and to assess the
      potential role of symbiotic bacteria. We show through electron microscopy that
      plant cell walls are visibly degraded in the bottom section of fungus gardens and
      refuse dumps, and that bacteria are more abundant in these sections. We also
      consistently isolated cellulolytic bacteria from all sections of fungus gardens.
      Finally, we show by culture-dependent and electron microscopy analysis that the
      fungus garden pellets carried by recently mated queens are colonized by fungus
      garden-associated bacteria. Taken together, our results indicate that cellulose
      is degraded in fungus gardens, and that fungus garden bacteria that may
      contribute to this deconstruction are vertically transmitted by new queens.

PMID- 29034863
TI  - The O-antigen structure of bacterium Comamonas aquatica CJG.
AB  - Genus Comamonas is a group of bacteria that are able to degrade a variety of
      environmental waste. Comamonas aquatica CJG (C. aquatica) in this genus is able
      to absorb low-density lipoprotein but not high-density lipoprotein of human
      serum. Using 1H and 13C NMR spectroscopy, we found that the O-polysaccharide (O
      antigen) of this bacterium is comprised of a disaccharide repeat (O-unit) of d
      glucose and 2-O-acetyl-l-rhamnose, which is shared by Serratia marcescens O6. The
      O-antigen gene cluster of C. aquatica, which is located between coaX and tnp4
      genes, contains rhamnose synthesis genes, glycosyl and acetyl transferase genes,
      and ATP-binding cassette transporter genes, and therefore is consistent with the
      O-antigen structure determined here.

PMID- 29034864
TI  - Evaluation of two commercial real-time PCR assays for detection of carbapenemase
      genes in Enterobacteriaceae.
AB  - The implementation of PCR for the detection of carbapenemase genes enables rapid
      results with significant epidemiological implications. Two commercial real-time
      PCR assays, the Hylabs Hy-CRE and Sacace MDR MBL+KPC/OXA, were evaluated for the
      detection of the genes blaKPC, blaVIM, blaNDM, blaIMP and blaOXA-48
      carbapenemasein a collection of 96 carbapenem-resistant Enterobacteriaceae
      strains with different resistant mechanisms. Both assays exhibited excellent
      diagnostic performance, with 100 % sensitivity and specificity.

PMID- 29034865
TI  - Patients Attending Emergency Departments.
AB  - BACKGROUND: The number of patients in emergency departments has risen steadily in
      recent years, with a particular increase in patients not requiring urgent
      treatment. The aim of this study is to characterize this group of patients with
      respect to their sociodemographic features, health status, and reasons for
      attending an emergency department. METHODS: PiNo Nord is a cross-sectional
      observational study representing two full working weeks in five different
      hospitals. Patients were questioned in personal interviews, and medical diagnoses
      were documented. The data were analyzed with multivariate logistic regressions in
      mixed multilevel models. Predictors for the subjectively perceived treatment
      urgency were identified by stepwise backward selection. RESULTS: The 1175
      patients questioned had an average age of 41.8 years and 52.9% were male. 54.7%
      said the degree of their treatment urgency was low. 41.3% had visited the
      emergency department on their own initiative, 17.0% on the advice or referral of
      their primary care physician, and 8.0% on the advice or referral of a specialist.
      The strongest predictors for low subjective treatment urgency were
      musculoskeletal trauma (odds ratio [OR] 2.18), skin conditions (OR 2.15), and the
      momentary unavailability of a primary care physician (OR 1.70). CONCLUSION: More
      than half of the patients do not think their condition requires urgent treatment
      and thus do not meet the definition of a medical emergency. Patients' reasons for
      visiting the emergency department are varied; aside from the treatment urgency of
      the health condition itself, the reason may lie in perceived structural
      circumstances and individual preferences.

PMID- 29034866
TI  - The Health Effects of Aluminum Exposure.
AB  - BACKGROUND: Aluminum is regularly taken up with the daily diet. It is also used
      in antiperspirants, as an adjuvant for vaccination, and in desensitization
      procedures. In this review, we present the scientifically documented harmful
      effects of aluminum on health and the threshold values associated with them.
      METHODS: This review is based on publications retrieved by a selective search of
      the PubMed and SCOPUS databases on the topic of aluminum in connection with
      neurotoxicity, Alzheimer's disease, and breast cancer, as well as on the authors'
      personal experience in occupational and environmental medicine. RESULTS: The
      reference values for the internal aluminum load (<15 MUg/L in urine, <5 MUg/L in
      serum) are especially likely to be exceeded in persons with occupational
      exposure. The biological tolerance value for occupational exposure is 50 MUg of
      aluminum per gram of creatinine in the urine. For aluminum welders and workers in
      the aluminum industry, declining performance in neuropsychological tests
      (attention, learning, memory) has been found only with aluminum concentrations
      exceeding 100 MUg/g creatinine in the urine; manifest encephalopathy with
      dementia was not found. Elevated aluminum content has been found in the brains of
      persons with Alzheimer's disease. It remains unclear whether this is a cause or
      an effect of the disease. There is conflicting evidence on carcinogenicity. The
      contention that the use of aluminum-containing antiperspirants promotes breast
      cancer is not supported by consistent scientific data. CONCLUSION: The internal
      aluminum load is measured in terms of the concentration of aluminum in urine and
      blood. Keeping these concentrations below the tolerance values prevents the
      development of manifest and subclinical signs of aluminum toxicity. Large-scale
      epidemiologic studies of the relationship between aluminum-containing
      antiperspirants and the risk of breast cancer would be desirable.

PMID- 29034867
TI  - Pyogenic Granuloma of the Vermilion of the Upper Lip.

PMID- 29034868
TI  - Filamentary Keratitis as Indication.

PMID- 29034869
TI  - Further Symptoms of Sjogren's Syndrome.

PMID- 29034870
TI  - In Reply.

PMID- 29034871
TI  - A Rare Cause of Ileus in a Two-Year-Old Boy.

PMID- 29034872
TI  - Particularities of Goodpasture Syndrome.

PMID- 29034873
TI  - In Reply.

PMID- 29034875
TI  - Treatment of displaced intra-articular calcaneus fractures: a current concepts
      review.
AB  - Displaced Intra-Articular Calcaneus fractures (DIACFs) represent a source of
      tremendous disability to the patient, economic burden to the society and a
      treatment challenge to the average orthopaedic surgeon. To date, no single
      approach is universally applicable to all calcaneus fractures. Despite a plethora
      of published meta-analyses and recent randomized controlled trials, the
      literature is still unclear and offers conflicting recommendations. The aim of
      this current concepts review is to assess the latest available data and offer
      pragmatic and practical recommendations to address some of the issues surrounding
      DIACFs.

PMID- 29034874
TI  - Pathogenesis of Plasmodium berghei ANKA infection in the gerbil (Meriones
      unguiculatus) as an experimental model for severe malaria.
AB  - BACKGROUND: As the quest to eradicate malaria continues, there remains a need to
      gain further understanding of the disease, particularly with regard to
      pathogenesis. This is facilitated, apart from in vitro and clinical studies,
      mainly via in vivo mouse model studies. However, there are few studies that have
      used gerbils (Meriones unguiculatus) as animal models. Thus, this study is aimed
      at characterizing the effects of Plasmodium berghei ANKA (PbA) infection in
      gerbils, as well as the underlying pathogenesis. METHODS: Gerbils, 5-7 weeks old
      were infected by PbA via intraperitoneal injection of 1 * 106 (0.2 mL) infected
      red blood cells. Parasitemia, weight gain/loss, hemoglobin concentration, red
      blood cell count and body temperature changes in both control and infected groups
      were monitored over a duration of 13 days. RNA was extracted from the brain,
      spleen and whole blood to assess the immune response to PbA infection. Organs
      including the brain, spleen, heart, liver, kidneys and lungs were removed
      aseptically for histopathology. RESULTS: Gerbils were susceptible to PbA
      infection, showing significant decreases in the hemoglobin concentration, RBC
      counts, body weights and body temperature, over the course of the infection.
      There were no neurological signs observed. Both pro-inflammatory (IFNgamma and
      TNF) and anti-inflammatory (IL-10) cytokines were significantly elevated.
      Splenomegaly and hepatomegaly were also observed. PbA parasitized RBCs were
      observed in the organs, using routine light microscopy and in situ hybridization.
      CONCLUSION: Gerbils may serve as a good model for severe malaria to further
      understand its pathogenesis.

PMID- 29034877
TI  - Generation of an induced pluripotent stem cell (iPSC) line from a patient with
      autosomal dominant retinitis pigmentosa due to a mutation in the NR2E3 gene.
AB  - A human iPSC line was generated from fibroblasts of a patient affected with
      autosomal dominant Retinitis Pigmentosa (RP) carrying the mutation p.Gly56Arg in
      the NR2E3 gene. The transgene-free iPSCs were generated with the human OSKM
      transcription factors using the Sendai-virus reprogramming system. iPSCs
      contained the expected c.166G>A substitution in exon 2 of NR2E3, expressed the
      expected pluripotency markers, displayed in vivo differentiation potential to the
      three germ layers and had normal karyotype. This cellular model will provide a
      powerful tool to study the pathogenesis of NR2E3-associated RP. Resource table.

PMID- 29034876
TI  - Quantifying the contribution of Plasmodium falciparum malaria to febrile illness
      amongst African children.
AB  - Suspected malaria cases in Africa increasingly receive a rapid diagnostic test
      (RDT) before antimalarials are prescribed. While this ensures efficient use of
      resources to clear parasites, the underlying cause of the individual's fever
      remains unknown due to potential coinfection with a non-malarial febrile illness.
      Widespread use of RDTs does not necessarily prevent over-estimation of clinical
      malaria cases or sub-optimal case management of febrile patients. We present a
      new approach that allows inference of the spatiotemporal prevalence of both
      Plasmodium falciparum malaria-attributable and non-malarial fever in sub-Saharan
      African children from 2006 to 2014. We estimate that 35.7% of all self-reported
      fevers were accompanied by a malaria infection in 2014, but that only 28.0% of
      those (10.0% of all fevers) were causally attributable to malaria. Most fevers
      among malaria-positive children are therefore caused by non-malaria illnesses.
      This refined understanding can help improve interpretation of the burden of
      febrile illness and shape policy on fever case management.

PMID- 29034879
TI  - Induced pluripotent stem cells derived from an autosomal dominant lateral
      temporal epilepsy (ADLTE) patient carrying S473L mutation in leucine-rich glioma
      inactivated 1 (LGI1).
AB  - Autosomal dominant lateral temporal epilepsy (ADLTE) is an inherited epileptic
      syndrome, and it is associated with mutations of leucine-rich glioma inactivated
      1 (LGI1) gene. The underlying mechanisms of ADLTE are still unknown, as human
      neurons are difficult to obtain as a research tool. Human induced pluripotent
      stem cells (iPSCs) allow the generation of patient-derived neuronal cells in a
      dish, and can be a promising tool to model ADLTE. Here, we report the
      establishment of human iPSCs from an ADLTE patient carrying LGI1 mutation
      (c.1418C>T, p.Ser473Leu).

PMID- 29034878
TI  - Generation of an induced pluripotent stem cell line (CSCRMi001-A) from a patient
      with a new type of limb-girdle muscular dystrophy (LGMD) due to a missense
      mutation in POGLUT1 (Rumi).
AB  - Recently, a new type of limb-girdle muscular dystrophy (LGMD type 2Z) has been
      identified due to a missense mutation in POGLUT1 (protein O-glucosyltransferase
      Rumi), an enzyme capable of adding glucose to a distinct serine residue of
      epidermal growth factor-like repeats containing a C-X-S-X-(P/A)-C consensus
      sequence such as Notch receptors. Affected patients demonstrate reduced Notch
      signaling, decreased muscle stem cell pool and hypoglycosylation of alpha
      dystroglycan, leading to LGMD phenotype. Here we report the generation and
      characterization of an iPSC line (CSCRMi001-A) from a LGMD-2Z patient with
      missense mutation in POGLUT1 which can be used for in vitro disease modeling.

PMID- 29034880
TI  - Generation of induced pluripotent stem cell (iPSC) line from a patient with
      triple negative breast cancer with hereditary exon 17 deletion of BRCA1 gene.
AB  - BRCA1 germline mutation confers hereditary predisposition for breast and ovarian
      cancer. To understand the physiopathology of mammary and ovarian epithelial
      cancer transformation, and to identify early driver molecular events, we have
      generated an iPSC line from a patient carrying a germline exon 17 deletion in
      BRCA1 gene (BRAC1Ex17 iPSC) in a high-risk family context. Blood cells were
      reprogrammed used non-integrative virus of Sendai. The BRCA1-deleted iPSC had
      normal karyotype, harboured a deletion in the exon 17 of the BRCA1 gene,
      expressed pluripotent hallmarks and had the differentiation capacity into the
      three germ layers.

PMID- 29034881
TI  - Generation of induced pluripotent stem cells derived from an autosomal dominant
      polycystic kidney disease patient with a p.Ser1457fs mutation in PKD1.
AB  - Autosomal dominant polycystic kidney disease is one of the most prevalent forms
      of inherited cystic kidney disease, and can be characterized by kidney cyst
      formation and enlargement. Here we report the generation of a Type 1 ADPKD
      disease iPS cell line, IBMS-iPSC-012-12, which retains the conserved deletion of
      PKD1, normal karyotype and exhibits the properties of pluripotent stem cells such
      as ES-like morphology, expression of pluripotent markers and capacity to
      differentiate into all three germ layers. Our results show that we have
      successfully generated a patient-specific iPS cell line with a mutation in PKD1
      for study of renal disease pathophysiology.

PMID- 29034882
TI  - Generation of human induced pluripotent stem cell lines from human dermal
      fibroblasts using a modified RNA system.
AB  - We generated human induced pluripotent stem cells (KSCBi002-B and KSCBi002-B-1)
      from the dermal fibroblasts of a donor using a modified RNA-based gene delivery
      method. According to GTG-banding analysis, the generated KSCBi002-B line has a
      cytogenetic abnormality (46,XY, t(1;4)(q21;q25)) that is distinct from that of
      the donor, whereas KSCBi002-B-1 has a normal karyotype (46,XY). These cell lines
      can be useful as a model for characterizing the hiPSCs generated by a non-viral
      and non-integrative system, or as a chromosomal balanced translocation model.
      These two cell lines are registered and available from the National Stem Cell
      Bank, Korea National Institute of Health.

PMID- 29034883
TI  - Establishment of a congenital tooth agenesis related gene MSX1 knockout human
      embryonic stem cell lines by CRISPR-Cas9 technology.
AB  - Human MSX1 gene is mapped to chromosome 4 and encodes a 303aa homeobox protein
      MSX1. MSX1 expression appears during early tooth development of vertebrate
      embryogenesis. Mutations in this protein are related to human tooth anomalie,
      cleft lip and palate and congenital ectodermal dysplasia syndrome. Most of the
      confirmed pathogenic mutations are located in exon2 encoded homeobox domain.
      Here, we report the establishment of MSX1 gene knockout human embryonic stem
      (hES) cell lines by CRISPR-Cas9 technology. These cell lines provide good
      materials for further studies of the roles MSX1 plays in human tooth development
      and congenital tooth agenesis.

PMID- 29034884
TI  - Generation of six multiple sclerosis patient-derived induced pluripotent stem
      cell lines.
AB  - Multiple sclerosis (MS) is considered a chronic autoimmune disease of the central
      nervous system that leads to gliosis, demyelination, axonal damage and neuronal
      death. The MS disease aetiology is unknown, though a polymorphism of the TNFRSF1A
      gene, rs1800693, is known to confer an increased risk for MS. Using retroviral
      delivery of reprogramming transgenes, we generated six MS patient-specific iPSC
      lines with two distinct genotypes, CC or TT, of the polymorphism rs1800693. iPSC
      lines had normal karyotype, expressed pluripotency genes and differentiated into
      the three germ layers. These lines offer a good tool to study MS pathomechanisms
      and for drug testing.

PMID- 29034885
TI  - Generation and characterization of a human induced pluripotent stem (iPS) cell
      line derived from an acute myeloid leukemia patient evolving from primary
      myelofibrosis carrying the CALR 52bp deletion and the ASXL1 p.R693X mutation.
AB  - Peripheral blood sample was donated by a 61years old female patient diagnosed
      with acute myeloid leukemia secondary to a primary myelofibrosis harboring the 52
      bp deletion in the CALR gene (c.1092_1143del, p.L367fs*46) and the R693X mutation
      in the ASXL1 gene (c.2077C>T, p.R693X). CD34+ cells were isolated from the sample
      and subjected to the reprogramming procedure by using the Sendai virus carrying
      the reprogramming factors Oct3/4, Sox2, Klf4 and c-Myc. iPS colonies generated
      retained the original mutations and displayed all the features of bona fide iPS
      cells.

PMID- 29034886
TI  - Generation and characterization of human induced pluripotent stem cell (hiPSC)
      lines from an Alzheimer's disease (ASUi001-A) and non-demented control (ASUi002
      A) patient homozygous for the Apolipoprotein e4 (APOE4) risk variant.
AB  - Although the majority of late-onset Alzheimer's disease (AD) patients are labeled
      sporadic, multiple genetic risk variants have been identified, the most powerful
      and prevalent of which is the e4 variant of the Apolipoprotein E (APOE) gene.
      Here, we generated human induced pluripotent stem cell (hiPSC) lines from the
      peripheral blood mononuclear cells (PBMCs) of a clinically diagnosed AD patient
      [ASUi001-A] and a non-demented control (NDC) patient [ASUi002-A] homozygous for
      the APOE4 risk allele. These hiPSCs maintained their original genotype, expressed
      pluripotency markers, exhibited a normal karyotype, and demonstrated the ability
      to differentiate into cells representative of the three germ layers.

PMID- 29034887
TI  - Generation of three miR-122 knockout lines from a human embryonic stem cell line.
AB  - miR-122 is the most abundant miRNA in the human liver, accounting for 52% of the
      entire hepatic miRNome. Previous studies have demonstrated that miR-122 plays key
      roles in hepatocyte growth, metabolism, and homeostasis. Here, we created three
      miR-122 knockout human embryonic stem cell line lines, WAe001-A-7, WAe001-A-8,
      and WAe001-A-9, using the CRISPR/Cas9 technique. These mutated cell lines
      retained their pluripotency, in vitro differentiation potential, normal
      morphology, and karyotype.

PMID- 29034888
TI  - Generation of two MEN1 knockout lines from a human embryonic stem cell line.
AB  - The MEN1 gene is cytogenetically located at 11q13.1 and encodes the nuclear
      protein menin, which is involved in cell proliferation, apoptosis,
      differentiation, and metabolism. Here, we generated two MEN1 knockout human
      embryonic stem cell lines, WAe001-A-4 and WAe001-A-5, by targeting exon-2 and
      exon-9 of MEN1 using the CRISPR/Cas9 technique. These cell lines maintained their
      pluripotency, in vitro differentiation potential, normal morphology, and
      karyotype. These human MEN1-mutated cell lines not only enlarge the pool of lab
      resources but also provide ideal models to dissect the detailed physio
      pathological roles of the menin protein.

PMID- 29034889
TI  - Generation of a pig induced pluripotent stem cell (piPSC) line from embryonic
      fibroblasts by incorporating LIN28 to the four transcriptional factor-mediated
      reprogramming: VSMUi001-D.
AB  - Pig induced pluripotent stem cell (piPSC) line was generated from embryonic
      fibroblast cells using retroviral transduction approaches carrying human
      transcriptional factors: OCT4, SOX2, KLF4, c-MYC and LIN28. The generated piPSC
      line, VSMUi001-D, was positive for alkaline phosphatase activity and expressed
      the pluripotency associated transcription factors including OCT4, SOX2, NANOG and
      surface markers SSEA-1, all iPSC hallmarks of authenticity. Furthermore, VSMUi001
      D exhibited a normal karyotype and formed embryoid bodies in vitro and teratomas
      in vivo. Upon cardiac differentiation, VSMUi001-D displayed spontaneous beating
      and expressed cardiomyocyte markers, like cardiac Troponin T.

PMID- 29034890
TI  - Derivation of a disease-specific human induced pluripotent stem cell line from a
      biliary atresia patient.
AB  - Biliary atresia (BA) is a common cause of pediatric end-stage liver disease.
      While its etiology is not yet clear, evidence has suggested that BA results from
      interactions between genetic susceptibility and environmental factors. Disease
      relevant human cellular models of BA will facilitate identification of both
      genetic and environmental factors that are important for disease prevention and
      treatment. Here we report the generation of a human induced pluripotent stem cell
      line from a BA patient using episomal vectors. Patient-specific BA iPSC lines
      provide valuable tools for disease mechanism study and drug development.

PMID- 29034891
TI  - Generation of induced pluripotent stem cells (iPSC) from an atrial fibrillation
      patient carrying a KCNA5 p.D322H mutation.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia associated with
      several cardiac risk factors, but increasing evidences indicated a genetic
      component. Indeed, genetic variations of the atrial specific KCNA5 gene have been
      identified in patients with early-onset lone AF. To investigate the molecular
      mechanisms underlying AF, we reprogrammed to pluripotency polymorphonucleated
      leukocytes isolated from the blood of a patient carrying a KCNA5 p.D322H
      mutation, using a commercially available non-integrating system. The generated
      iPSCs expressed pluripotency markers and differentiated toward cells belonging to
      the three embryonic germ layers. Moreover, the cells showed a normal karyotype
      and retained the p.D322H mutation.

PMID- 29034892
TI  - Generation of a human induced pluripotent stem cell line from a 65-year old
      healthy female donor with Chinese Han genetic background.
AB  - Peripheral blood mononuclear cells (PBMC) were collected from a 65-year old
      healthy woman with Chinese Han genetic background. The PBMCs were reprogrammed
      with the human OKSM transcription factors using the non-integrating episomal
      vector system. The transgene-free iPSC showed pluripotency verified by
      immunocytochemistry for pluripotency markers and differentiated spontaneously
      toward the 3 germ layers in vitro. Furthermore, the iPSC line showed normal
      karyotype. The iPSC line can be used as control in disease mechanism studies.
      Resource table.

PMID- 29034893
TI  - Establishment of DYT5 patient-specific induced pluripotent stem cells with a GCH1
      mutation.
AB  - Peripheral blood mononuclear cells (PBMCs) were collected from a clinically
      diagnosed 20-year-old dystonia patient with a GCH1 mutation (DYT5). Episomal
      vectors were used to introduce reprogramming factors (OCT3/4, SOX2, KLF4, L-MYC,
      LIN28, and p53 carboxy-terminal dominant-negative fragment) to the PBMCs. The
      generated iPSCs expressed pluripotency markers, and were capable of
      differentiating into derivates of all three germ layers in vitro. The iPSC line
      also showed a normal karyotype and preserved the GCH1 mutation. This cellular
      model can provide opportunities to perform pathophysiological studies for
      aberrant dopamine metabolism-related disorders.

PMID- 29034894
TI  - Induced pluripotent stem cells derived from a patient with familial idiopathic
      basal ganglia calcification (IBGC) caused by a mutation in SLC20A2 gene.
AB  - Idiopathic basal ganglia calcification (IBGC), also known as Fahr disease or
      primary familial brain calcifications (PFBC), is a rare neurodegenerative
      disorder characterized by calcium deposits in basal ganglia and other brain
      regions, causing neuropsychiatric and motor symptoms. We established human
      induced pluripotent stem cells (iPSCs) from an IBGC patient. The established IBGC
      iPSCs carried SLC20A2 c.1848G>A mutation (p.W616* of translated protein PiT2),
      and also showed typical iPSC morphology, pluripotency markers, normal karyotype,
      and the ability of in vitro differentiation into three-germ layers. The iPSC line
      will be useful for further elucidating the pathomechanism and/or drug development
      for IBGC.

PMID- 29034895
TI  - Generation of induced pluripotent stem cell (iPSC) line from Charcot-Marie-Tooth
      disease patient with MPZ mutation (CMT1B).
AB  - Charcot-Marie-Tooth disease (CMT1B) is an inherited neurological disorder caused
      by mutation of the myelin protein zero (MPZ) gene. We generated an induced
      pluripotent stem cell (iPSC) line from an 81-year-old patient with CMT1B by
      electroporating of lymphoblastoid cell lines with episomal plasmids encoding
      OCT4, SOX2, KLF4, L-MYC, LIN28, and p53-targeting shRNA. The established iPSCs
      expressed various pluripotency markers, demonstrated the potential to
      differentiate into cells of the three germ layers in vitro, had a normal
      karyotype and retained the MPZ mutation.

PMID- 29034897
TI  - Generation of iPSC line from desmin-related cardiomyopathy patient carrying
      splice site mutation of DES gene.
AB  - Human iPSC line was generated from patient-specific adipose tissue-derived
      mesenchymal multipotent stromal cells carrying desmin (DES) gene heterozygous
      splice site mutation using non-integrative reprogramming method. Reprogramming
      factors OCT4, KLF4, SOX2, CMYC were delivered using Sendai viruses. iPSCs were
      characterized by sequencing, karyotype analysis, STR analysis,
      immunocytochemistry, RT-PCR and teratoma formation.

PMID- 29034896
TI  - Generation of induced pluripotent stem cells (ARO-iPSC1-11) from a patient with
      autosomal recessive osteopetrosis harboring the c.212+1G>T mutation in SNX10
      gene.
AB  - Pathogenic sequence variants in the Sorting Nexin 10 (SNX10) gene have been
      associated with autosomal recessive osteopetrosis (ARO) in human. In this study,
      an induced pluripotent stem cell (iPSC) line (ARO-iPSC1-11) was generated from an
      ARO patient carrying the homozygous c.212+1G>T mutation in SNX10, using a
      retroviral-based reprogramming protocol. Characterization confirmed that the
      generated iPSCs expressed pluripotency markers, displayed normal karyotype,
      showed pluripotent differentiation capacity and retained the targeted mutation.
      Disease modeling with this ARO patient-specific iPSC line will shed further light
      on the critical role of the SNX10 mutation in ARO development.

PMID- 29034898
TI  - Generation of induced pluripotent stem cells (iPSC) from an atrial fibrillation
      patient carrying a PITX2 p.M200V mutation.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia associated with
      several cardiac risk factors, but increasing evidences indicated a genetic
      component. Indeed, genetic variations of the specific PITX2 gene have been
      identified in patients with early-onset AF. To investigate the molecular
      mechanisms underlying AF, we reprogrammed to pluripotency polymorphonucleated
      leukocytes isolated from the blood of a patient carrying a PITX2 p.M200V
      mutation, using a commercially available non-integrating expression system. The
      generated iPSCs expressed pluripotency markers and differentiated toward cells
      belonging to the three embryonic germ layers. Moreover, the cells showed a normal
      karyotype and retained the PITX2 p.M200V mutation.

PMID- 29034899
TI  - Establishment of a human DOA 'plus' iPSC line, IISHDOi003-A, with the mutation in
      the OPA1 gene: c.1635C>A; p.Ser545Arg.
AB  - We have generated a human iPSC line IISHDOi003-A from fibroblasts of a patient
      with a dominant optic atrophy 'plus' phenotype, harbouring a heterozygous
      mutation, c.1635C>A; p.Ser545Arg, in the OPA1 gene. Reprogramming factors Oct3/4,
      Sox2, Klf4, and c-Myc were delivered using Sendai virus.

PMID- 29034900
TI  - Generation of iPSC line from patient with arrhythmogenic right ventricular
      cardiomyopathy carrying mutations in PKP2 gene.
AB  - Human iPSC line was generated from patient-specific adipose tissue-derived
      mesenchymal multipotent stromal cells carrying two mutations in plakophilin-2
      (PKP2) gene using non-integrative reprogramming method. Reprogramming factors
      OCT4, KLF4, SOX2, CMYC were delivered using Sendai viruses. Pluripotency was
      confirmed in vitro using immunofluorescence and RT-PCR analysis and in vivo by
      teratoma assay. The reported iPSC line could be useful tool for in vitro modeling
      of arrhythmogenic right ventricular cardiomyopathy.

PMID- 29034902
TI  - A robust statistical framework for instantaneous electroencephalogram phase and
      frequency estimation and analysis.
AB  - OBJECTIVE: The instantaneous phase (IP) and instantaneous frequency (IF) of the
      electroencephalogram (EEG) are considered as notable complements for the EEG
      spectrum. The calculation of these parameters commonly includes narrow-band
      filtering, followed by the calculation of the signal's analytical form. The
      calculation of the IP and IF is highly susceptible to the filter parameters and
      background noise level, especially in low analytical signal amplitudes. The
      objective of this study is to propose a robust statistical framework for EEG
      IP/IF estimation and analysis. APPROACH: Herein, a Monte Carlo estimation scheme
      is proposed for the robust estimation of the EEG IP and IF. It is proposed that
      any EEG phase-related inference should be reported as an average with confidence
      intervals obtained by repeating the IP and IF estimation under infinitesimal
      variations (selected by an expert), in algorithmic parameters such as the
      filter's bandwidth, center frequency and background noise level. In the second
      part of the paper, a stochastic model consisting of the superposition of narrow
      band foreground and background EEG is used to derive analytically probability
      density functions of the instantaneous envelope (IE) and IP of EEG signals, which
      justify the proposed Monte Carlo scheme. MAIN RESULTS: The instantaneous
      analytical envelope of the EEG, which has been empirically used in previous
      studies, is shown to have a fundamental impact on the accuracy of the EEG phase
      contents. It is rigorously shown that the IP/IF estimation quality highly depends
      on the IE and any phase/frequency interpretations in low IE are statistically
      unreliable and require a hypothesis test. SIGNIFICANCE: The impact of the
      proposed method on previous studies, including time-domain phase synchrony, phase
      resetting, phase locking value and phase amplitude coupling are studied with
      examples. The findings of this research can set forth new standards for EEG
      phase/frequency estimation and analysis techniques.

PMID- 29034903
TI  - Swimming without a spine: computational modeling and analysis of the swimming
      hydrodynamics of the Spanish Dancer.
AB  - Incompressible flow simulations are used to study the swimming of a Spanish
      Dancer (Hexabranchus sanguineus), a soft-bodied invertebrate marine gastropod
      that swims by combining body pitching with undulations of its large mantle. A
      simple model based on a field video is employed as the basis for the model and
      coupling of the flow with the body acceleration enables us to examine the free
      swimming of this animal. Simulations indicate propulsive efficiencies up to about
      57% and terminal swimming speeds of 1.33 body lengths per cycle. Examination of
      the effect of body planform on the swimming hydrodynamics suggests that the
      planform of this animal is likely adapted to enhance its swimming performance.

PMID- 29034901
TI  - Generation of a KCNJ11 homozygous knockout human embryonic stem cell line WAe001
      A-12 using CRISPR/Cas9.
AB  - The ATP-sensitive potassium channel is an octameric complex, and one of its
      subunits, namely Kir6.2, is encoded by the KCNJ11 gene. Mutations in KCNJ11
      result in hyperinsulinism or diabetes mellitus, associated with abnormal insulin
      secretion. Here, using CRISPR/Cas9 editing, we established a homozygous mutant
      KCNJ11 cell line, WAe001-A-12, which was generated by a 62-bp deletion in the
      coding sequence of the human embryonic stem cell line H1. It was confirmed that
      this deletion in the KCNJ11 gene did not affect the protein expression levels of
      key pluripotent factors. Additionally, normal karyotype and differentiation
      potency were observed for the cell line.

PMID- 29034904
TI  - Structural, magnetic and electronic properties of pulsed-laser-deposition grown
      SrFeO<sub>3-delta</sub> thin films and SrFeO<sub>3-delta</sub>
      /La<sub>2/3</sub>Ca<sub>1/3</sub>MnO<sub>3</sub> multilayers.
AB  - We studied the structural, magnetic and electronic properties of SrFeO<sub>3
      delta</sub> (SFO) thin films and SrFeO<sub>3-delta</sub>
      /La<sub>2/3</sub>Ca<sub>1/3</sub>MnO<sub>3</sub> (LCMO) superlattices that have
      been grown with pulsed laser deposition (PLD) on
      La<sub>0.3</sub>Sr<sub>0.7</sub>Al<sub>0.65</sub>Ta<sub>0.35</sub>O<sub>3</sub>
      (LSAT) substrates. X-ray reflectometry and scanning transmission electron
      microscopy (STEM) confirm the high structural quality of the films and flat and
      atomically sharp interfaces of the superlattices. The STEM data also reveal a
      difference in the interfacial layer stacking with a SrO layer at the LCMO/SFO and
      a LaO layer at the SFO/LCMO interfaces along the PLD growth direction. The X-ray
      diffraction (XRD) data suggest that the as grown SFO films and SFO/LCMO
      superlattices have an oxygen-deficient SrFeO<sub>3-delta</sub> structure with I4/
      mmm space group symmetry delta <= 0.2). Subsequent ozone annealed SFO films are
      consistent with an almost oxygen stoichiometric structure (delta ~ 0). The
      electronic and magnetic properties of these SFO films are similar to the ones of
      corresponding single crystals. In particular, the as grown SrFeO<sub>3
      delta</sub> films are insulating whereas the ozone annealed films are metallic.
      The magneto-resistance effects of the as grown SFO films have a similar magnitude
      as in the single crystals, but extend over a much wider temperature range. Last
      but not least, for the SFO/LCMO superlattices we observe a rather large exchange
      bias effect that varies as a function of the cooling field.

PMID- 29034906
TI  - Neuroimmunology: ILC2s touch a nerve.

PMID- 29034907
TI  - Immune tolerance: A mother's greatest gift is TIM3.

PMID- 29034908
TI  - Author's Response to Letter to the Editor: Cerebral Hemorrhage Following
      Chiropractic Activator Treatment-Case Report and Review of the Literature.

PMID- 29034909
TI  - A universal and enzyme-free immunoassay platform for biomarker detection based on
      gold nanoparticle enumeration with a dark-field microscope.
AB  - Developing an enzyme-free, non-amplification strategy for biomarker detection
      with universality and easy implementation is of central importance in clinical
      diagnosis and therapeutic monitoring. Herein, we report for the first time a
      universal and enzyme-free magnetic bead-based sandwich-format immunoassay
      platform for biomarker detection by combining secondary antibody functionalized
      AuNPs and automatic AuNP counting readout. For the prostate specific antigen
      (PSA), the detection limit is found to be 1 ng mL-1, and the spike recoveries (n
      = 3) with 10% fetal bovine serum are 113.5% for 2 ng mL-1 and 107.7% for 10 ng mL
      1. The assay also presents reasonable repeatability as indicated by the
      coefficient of variance of 13.1% with 5 measurements in 60 days. This strategy
      has been successfully applied to the determination of carcinoembryonic antigen
      (CEA) and alpha-fetoprotein (AFP), demonstrating the universality of this
      strategy. Our proposed non-amplification platform presents sensitivity comparable
      to that of the enzyme-linked immunosorbent assay (ELISA) with better
      repeatability; and more importantly, our method has better simplicity than most
      of the amplification-based methods, and thus is more suitable for routine
      analysis. The highlights of our work suggest that it is a promising method and
      would be potentially an alternative for ELISA in laboratories where routine
      analyses are intensively performed.

PMID- 29034910
TI  - From boron clusters to gold clusters: new label-free colorimetric sensors.
AB  - A fundamental boron cluster, [closo-B12H12]2-, mainly known as an inert agent for
      boron neutron capture therapy, can also serve as a bi-functional reductant and a
      capping agent for the formation of monodispersed size-controlled gold
      nanoparticles (AuNPs) under mild reaction conditions. The obtained AuNPs remained
      thermo-dynamically stable over 3 months, and exhibited high performance in phase
      transfer and sensing of heavy metal ions.

PMID- 29034911
TI  - Collision cross sections and ion structures: development of a general calculation
      method via high-quality ion mobility measurements and theoretical modeling.
AB  - Ion mobility mass spectrometry (IM-MS) has become an important tool for the
      structural investigation of ions in the gas phase. Accurate theoretical
      evaluation of ion collision cross sections (CCSs) is essential for the effective
      application of IM-MS in structural studies. However, current theoretical tools
      have limitations in accurately describing a broad range of ions from small
      molecules to macromolecules. Significant difficulties in developing theoretical
      tools for CCS calculations are associated with obtaining high-quality
      experimental data and molecular models. In this study, we present a general CCS
      calculation method by employing two drift-tube IM-MS (DTIM-MS) instruments and
      thorough molecular modeling procedures. It is demonstrated that an appropriate
      description of the van der Waals (vdW) interactions is important for accurate CCS
      calculations in helium drift gas. By utilizing the vdW potentials from molecular
      mechanics force fields, it is shown that both the appropriate vdW potential-forms
      and their parameters are necessary for the highly reliable CCS predictions of
      small molecules. We further show that specific characteristics of the vdW
      interaction potential become less influential on the calculated CCS with
      increasing ion size, and that the calculated CCS values for the macromolecules
      converge to the values at the hard-sphere limit. Based on these results, a
      general CCS calculation method is presented that can be applied to ions of
      various sizes and compositions for the gas-phase structural studies.

PMID- 29034905
TI  - The hygiene hypothesis in autoimmunity: the role of pathogens and commensals.
AB  - The incidence of autoimmune diseases has been steadily rising. Concomitantly, the
      incidence of most infectious diseases has declined. This observation gave rise to
      the hygiene hypothesis, which postulates that a reduction in the frequency of
      infections contributes directly to the increase in the frequency of autoimmune
      and allergic diseases. This hypothesis is supported by robust epidemiological
      data, but the underlying mechanisms are unclear. Pathogens are known to be
      important, as autoimmune disease is prevented in various experimental models by
      infection with different bacteria, viruses and parasites. Gut commensal bacteria
      also play an important role: dysbiosis of the gut flora is observed in patients
      with autoimmune diseases, although the causal relationship with the occurrence of
      autoimmune diseases has not been established. Both pathogens and commensals act
      by stimulating immunoregulatory pathways. Here, I discuss the importance of
      innate immune receptors, in particular Toll-like receptors, in mediating the
      protective effect of pathogens and commensals on autoimmunity.

PMID- 29034912
TI  - Shape effect-induced spiral superstructures in a self-assembled achiral disc-bent
      core amphiphile.
AB  - Herein, we aim to demonstrate the shape effect of a giant molecule on the self
      assembly of supramolecules. A bent-core (BC) molecule was covalently linked to a
      disc-like hexa-peri-hexabenzocoronene (HBC), giving a disc-bent core amphiphile.
      As a result, the induced hierarchical chirality driven by the shape effect on the
      forming columnar phase gives a two-dimensional nano-ribbon with spiral texture
      from double-stranded supracolumns.

PMID- 29034913
TI  - A proton-hopping charge storage mechanism of ionic one-dimensional coordination
      polymers for high-performance supercapacitors.
AB  - A proton-conducting coordination polymer of anionic one-dimensional (1D) chains
      of Zn2+ phosphate and protonated imidazole with the formula of
      [Zn(HPO4)(H2PO4)2](ImH2)2 has been used as a novel supercapacitor material in
      aqueous electrolytes. This material stores charges via a proton-hopping
      mechanism.

PMID- 29034914
TI  - Local water sensing: water exchange in bacterial photosynthetic reaction centers
      embedded in a trehalose glass studied using multiresonance EPR.
AB  - Using isotope labeled water (D2O and H217O) and pulsed W-band (94 GHz) high-field
      multiresonance EPR spectroscopies, such as ELDOR-detected NMR and ENDOR, the
      biologically important question of detection and quantification of local water in
      proteins is addressed. A bacterial reaction center (bRC) from Rhodobacter
      sphaeroides R26 embedded into a trehalose glass matrix is used as a model system.
      The bRC hosts the two native radical cofactor ions (primary electron donor) and
      (primary electron acceptor) as well as an artificial nitroxide spin label site
      specifically attached to the surface of the H-protein domain. The three
      paramagnetic reporter groups have distinctly different local environments. They
      serve as local probes to detect water molecules via magnetic interactions
      (electron-nuclear hyperfine and quadrupole) with either deuterons or 17O nuclei.
      bRCs were equilibrated in an atmosphere of different relative humidities allowing
      us to control precisely the hydration levels of the protein. We show that by
      using oxygen-17 labeled water quantitative conclusions can be made in contrast to
      using D2O which suffers from proton-deuterium exchange processes in the protein.
      From the experiments we also conclude that dry trehalose operates as an
      anhydrobiotic protein stabilizer in line with the "anchorage hypothesis" of bio
      protection. It predicts selective changes in the first solvation shell of the
      protein upon trehalose-matrix dehydration with subsequent changes in the hydrogen
      bonding network. Changes in hydrogen-bonding patterns usually have an impact on
      the global function of a biological system.

PMID- 29034915
TI  - Highly versatile heteroditopic ligand scaffolds for accommodating group 8, 9 & 11
      heterobimetallic complexes.
AB  - Two highly versatile xanthene scaffolds containing pairs of heteroditopic ligands
      were found to be capable of accommodating a range of transition metal ions,
      including Au(i), Ir(i), Ir(iii), Rh(i), and Ru(ii) to generate an array of
      heterobimetallic complexes. The metal complexes were fully characterised and
      proved to be stable in the solid and solution state, with no observed metal-metal
      scrambling. Heterobimetallic complexes containing the Rh(i)/Ir(i) combinations
      were tested as catalysts for the two-step dihydroalkoxylation reaction of
      alkynediols and sequential hydroamination/hydrosilylation reaction of
      alkynamines.

PMID- 29034916
TI  - Syntheses and characterization of three new sulfides with large band gaps:
      acentric Ba4Ga4SnS12, centric Ba12Sn4S23 and Ba7Sn3S13.
AB  - The desirable development of infrared nonlinear optical (IR NLO) materials is to
      design new compounds which exhibit wide band gaps and strong second harmonic
      generation (SHG) responses. Herein, we report three new sulfides, Ba4Ga4SnS12
      (1), Ba12Sn4S23 (2) and Ba7Sn3S13 (3), with wide band gaps of 2.90, 2.98 and 3.0
      eV, respectively, which have been successfully synthesized for the first time.
      Significantly, compound 1 exhibited a large SHG coefficient (34 * KDP),
      illustrating a good balance between the band gap and the SHG response. Single
      crystal X-ray diffraction determined that compound 1 crystallizes in the non
      centrosymmetric space group P4[combining macron]21c and it was characterized as
      an interesting kite-shaped linkage motif of infinity[Ga4SnS12]. Compounds 2 and 3
      crystallize in the space groups of P21c and Pnma, respectively. In addition,
      compounds 2 and 3 were characterized as zero-dimensional (0D) structures
      comprising isolated SnS4 tetrahedra with Ba2+ cations and S2- anions located
      between them. However, compound 2 contains extra disulfide S22- anions in its
      isolated structure. Moreover, the theoretical calculations demonstrated that SHG
      responses for compound 1 could be ascribed to the transitions from S-3p and Ga-4p
      states to Ba-5d, Ga-4p and Sn-5p states. By analysing the relationship between
      the structures and properties for Pb4Ga4GeS12-type compounds, it was concluded
      that site disorder could be an effective way to improve optical properties.

PMID- 29034917
TI  - beta-Sitosterol and stigmasterol ameliorate dextran sulfate sodium-induced
      colitis in mice fed a high fat Western-style diet.
AB  - Phytosterols, the plant analogues of cholesterol, widely occur in the human diet.
      In this study, we investigated and compared the effects of stigmasterol and beta
      sitosterol (both with purities >=95%) on dextran sulfate sodium (DSS)-induced
      colitis in C57BL/6J male mice fed a high fat Western-style diet. Mice treated
      with DSS developed severe mucosal colitis, with a marked distortion and crypt
      loss of colonic surface epithelium. Both beta-sitosterol and stigmasterol
      significantly inhibited colon shortening, lowered fecal hemoglobin content, and
      reduced the severity of colitis in the middle and distal colon (p < 0.05). These
      phytosterols also significantly suppressed the activation of nuclear factor-kappa
      B. They also significantly decreased colony stimulating factor-1 and the nuclear
      translocation of inflammatory master regulator nuclear factor-kappa B.
      Stigmasterol significantly lowered the colonic inflammation score and the
      expression of cyclooxygenase-2 and colony stimulating factor-1, while beta
      sitosterol was less or not effective. These results suggest that dietary intake
      of stigmasterol and beta-sitosterol ameliorates colitis. Such activities of
      stigmasterol and beta-sitosterol in humans remain to be investigated.

PMID- 29034918
TI  - Resveratrol: from diet to topical usage.
AB  - The stilbene derivative resveratrol (3,5,4'-trihydroxy-stilbene; RESV) has become
      the subject of interest of many researchers and the pharmaceutical industries due
      to its well-acclaimed beneficial biological activities. Although earlier research
      tended to focus on the effects of RESV on cardiovascular disorders, many other
      studies have described the beneficial effects of RESV in the areas of cancer
      chemoprevention and inflammation and interest of researchers on this compound is
      still increasing. It is now well accepted that the effect of RESV is not just due
      to its so called "antioxidant" activity but mainly (if not only) because of the
      ability of this compound to trigger cell signaling pathways and gene expression
      involved in cellular defense systems. Many "in vitro" studies on RESV did not
      take into account that although its oral absorption is about 75% it undergoes
      rapid metabolism and the concentration in the blood stream is almost
      undetectable. For this reason interest in the topical usage of RESV by
      cosmeceutical skin care brands has exponentially increased in the last decade
      reporting in general very promising results on its beneficial effect in
      protecting the skin from outdoor insults, but there is still some controversy on
      its topical usage mainly surrounding the concentration used. Therefore, more
      basic research on the topical application of RESV should be performed to better
      understand the way it prevents cutaneous damage and whether it could be
      recommended as a preventive skin aging agent for all skin insults.

PMID- 29034919
TI  - Supramolecular effects in self-assembled monolayers: general discussion.

PMID- 29034920
TI  - The active site for the water oxidising anodic iridium oxide probed through in
      situ Raman spectroscopy.
AB  - The structure of anodic iridium oxide (IrOx) under water oxidation was explored
      using in situ Raman spectroscopy and theoretical calculations. Isotopic
      substitution experiments and theoretical calculations confirmed formation of an
      Ir[double bond, length as m-dash]O species during oxygen evolution reaction.

PMID- 29034921
TI  - Targeted attachment of functional groups at Ge9 clusters via silylation
      reactions.
AB  - Molecules with low-valent Ge atoms are generally synthesized from organohalogen
      germanes as precursors. The Zintl phase K4Ge9 provides reactive building blocks
      for a targeted synthesis of germanium-rich molecules. The silylation of Ge9
      clusters with chlorosilanes ClSiR2R', that carry unsaturated olefin groups R'
      leads to the introduction of olefinic side chains of variable lengths allowing
      for further reactions. The compounds K[Ge9{Si(SiMe3)3}2(SiPh2R')] (R' = 
      CH[double bond, length as m-dash]CH2 (1); -(CH2)3CH[double bond, length as m
      dash]CH2 (2)) carry one such functionality, whereas K[Ge9(SiPh2R')3] (3 and 4)
      offer the possibility for an interconnection of clusters due to three functional
      groups on the Ge9 core. XPS measurements show that the silylated clusters are
      much more air-stable than the unsubstituted, bare cluster units.

PMID- 29034922
TI  - A new molecular design based on hybridized local and charge transfer fluorescence
      for highly efficient (>6%) deep-blue organic light emitting diodes.
AB  - A deep-blue emitter was developed by modifying carbazole nuclear positions C2 &
      C7 with a triphenylamine donor and C3 & C6 with a cyano acceptor. The molecular
      design features cross-conjugated localized and charge transfer chromophores which
      results in a hybridized local charge transfer (HLCT) excited state. An organic
      light emitting diode (OLED) using this material exhibited high external quantum
      efficiency (6.5%) with excellent color saturation (CIEy ~ 0.06) and small full
      width at half maximum (48 nm).

PMID- 29034923
TI  - Supramolecular systems at liquid-solid interfaces: general discussion.

PMID- 29034924
TI  - Trapping of superoxido cobalt and peroxido dicobalt species formed reversibly
      from CoII and O2.
AB  - The formation and spectroscopic characterization of a superoxido cobalt(iii) and
      a peroxido dicobalt(iii) species formed in the temperature dependent reversible
      reaction of a cobalt(ii) precursor with O2 is described. The electronic nature of
      each species is explored in their reactivity with organic substrates.

PMID- 29034925
TI  - Charge transport, interfacial interactions and synergistic mechanisms in
      BiNbO4/MWO4 (M = Zn and Cd) heterostructures for hydrogen production: insights
      from a DFT+U study.
AB  - In the 21st century, the growing demand of global energy is one of the key
      challenges. The photocatalytic generation of hydrogen has attracted extensive
      attention to discuss the increasing global demand for sustainable and clean
      energy. However, hydrogen evolution reactions normally use the economically
      expensive rare noble metals and the processes remain a challenge. Herein, low
      cost BiNbO4/MWO4(010) heterostructures are studied for the first time to check
      their suitability towards photocatalytic hydrogen production. A theoretical study
      with the aid of density functional theory (DFT) is used to investigate the
      synergistic effect, ionisation energy, electron affinities, charge transfer,
      electronic properties and the underlying mechanism for hydrogen generation of
      BiNbO4/MWO4(010) heterostructures. The experimental band gaps of bulk ZnWO4,
      CdWO4 and BiNbO4 are well reproduced using the DFT+U method. The calculated band
      edge position shows a type-II staggered band alignment and the charge transfer
      between BiNbO4 and MWO4 monolayers results in a large interfacial built-in
      potential, which will favour the separation of charge carriers in the
      heterostructures. The effective mass of the photoinduced holes is higher compared
      to the electrons, making the heterostructures useful in hydrogen production. The
      relatively low ionisation energy and electron affinity for the heterostructures
      compared to the monolayers make them ideal for photocatalysis applications due to
      their small energy barrier for the injection of electrons and creation of holes.
      The BiNbO4/MWO4(010) heterostructures are more suitable for photocatalytic
      hydrogen production due to their strong reducing power relative to the H+/H2O
      potential. This study sheds light on the less known BiNbO4/ZnWO4(010)
      heterostructures and the fully explored electronic and optical properties will
      pave way for future photocatalytic water splitting applications.

PMID- 29034926
TI  - Acid-etched layered double hydroxides with rich defects for enhancing the oxygen
      evolution reaction.
AB  - Water splitting is promising for energy storage and conversion, but the sluggish
      oxygen evolution reaction (OER) hinders its wide application. The search for
      efficient and low-cost electrocatalysts for oxygen evolution has been pursued
      owing to their significance for green energy generation and storage. Layered
      Double Hydroxide (LDH) based materials are promising for the OER to improve this
      weakness. However, the wide application of LDHs is limited by their electronic
      properties and active sites. Here we report a simple and promising method to
      improve the OER catalytic activity via an acid-base reaction, which resulted in
      an exfoliation process and multiple defects including Co, Fe and O vacancies. The
      acid etched LDHs exhibit better oxygen evolution performance than the pristine
      LDHs under alkaline conditions with a small Tafel slope and good durability. The
      acid etching improves the electronic structure and provides more active sites,
      which results in significant enhancement of OER activity. This work will open up
      a novel and inexpensive way to improve the catalytic performance in an alkaline
      substance.

PMID- 29034927
TI  - Exploring the role of GS-GOGAT cycle in microcystin synthesis and regulation - a
      model based analysis.
AB  - Toxic cyanobacteria blooms populate water bodies by consuming external nutrients
      and releasing cyanotoxins that are detrimental for other aquatic species,
      producing a significant impact on the plankton ecosystem and food web. To
      exercise population-level control of toxin production, understanding the
      biochemical mechanisms that explain cyanotoxin regulation within a bacterial cell
      is of utmost importance. In this study, we explore the mechanistic events to
      investigate the dependence of toxin microcystin on external nitrogen, a known
      regulator of the toxin, and for the first time, propose a kinetic model that
      analyzes the intracellular conditions required to ensure nitrogen dependence on
      microcystin. We hypothesize that the GS-GOGAT cycle is manipulated by variable
      influx of different intracellular metabolites that can either disturb or promote
      the balance between the enzyme microcystin synthetase and substrate glutamate to
      produce variable microcystin levels. As opposed to the popular notion that
      nitrogen starvation increases microcystin synthesis, our analyses suggest that
      under certain intracellular metabolite regimes, this relationship can either be
      completely lost or reversed. External nitrogen can only complement the conditions
      fixed by intracellular glutamate, glutamine and 2-oxoglutarate. This mechanistic
      understanding can provide an experimentally testable hypothesis for exploring the
      less-known biology of microcystin synthesis and designing specific interventions.

PMID- 29034928
TI  - Boosting up the electrical performance of low-grade PEDOT:PSS by optimizing non
      ionic surfactants.
AB  - Although PEDOT:PSS has already been applied to various electronic devices,
      commercialized PEDOT:PSS products having high conductivity are expensive, which
      is a considerable burden on device manufacturing. In this study, we optimize non
      ionic surfactants mixed in a PEDOT:PSS solution to upgrade a low-grade product of
      low conductivity to the level of a high-grade product of high conductivity. This
      study systematically investigates the phase diagram, morphology, conductivity,
      and mechanical stability of the PEDOT:PSS films according to the hydrophilicity
      of non-ionic surfactants. This study reveals that the conductivity of the
      PEDOT:PSS film varies greatly depending on the chemical structure of the
      surfactant and its weight fraction in the thin film. Under the optimum conditions
      (chemical structure and weight fraction) of the surfactant, the conductivity of
      the low value product could be improved to the conductivity level of the high
      value product. The electrical properties of the films were excellently stable
      even under the extreme cyclic bending tests at a bending radius of 1.5 mm. The
      low-grade and high grade products showed the same electrical performance when
      they were used in the Ag nanowires/PEDOT:PSS hybrid transparent electrodes. The
      results are expected to be applied immediately not only in the laboratory but
      also in various industrial fields.

PMID- 29034929
TI  - Wrinkling-to-delamination transition in thin polymer films on compliant
      substrates.
AB  - Compressing a thin, stiff film attached to a thick, compliant substrate can lead
      to a number of different modes of mechanical deformation depending upon the
      material properties of the system. In this article we explore direct transitions
      from surface wrinkling to buckle delamination, and provide a theoretical
      framework for understanding the conditions under which such transitions take
      place, as well as the resulting dimensions of the wrinkling-induced delamination.
      A key conclusion of this work is that the width of the delamination blister
      formed from a wrinkled film is relatively strain-independent, suggesting that
      delaminations can be used in such systems to measure the adhesion energy at the
      film-substrate interface. In addition, we demonstrate how the length and width of
      delaminations can be tailored through straightforward control of the substrate
      and film properties in the system, illustrating how wrinkling delaminations can
      be used for both thin film metrology and patterning applications.

PMID- 29034930
TI  - Chain dynamics and nanoparticle motion in attractive polymer nanocomposites
      subjected to large deformations.
AB  - The effect of large deformation on the chain dynamics in attractive polymer
      nanocomposites was investigated using neutron scattering techniques. Quasi
      elastic neutron backscattering measurements reveal a substantial reduction of
      polymer mobility in the presence of attractive, well-dispersed nanoparticles. In
      addition, large deformations are observed to cause a further slowing down of the
      Rouse rates at high particle loadings, where the interparticle spacings are
      slightly smaller than the chain dimensions, i.e. in the strongly confined state.
      No noticeable change, however, was observed for a lightly confined system. The
      reptation tube diameter, measured by neutron spin echo, remained unchanged after
      shear, suggesting that the level of chain-chain entanglements is not
      significantly affected. The shear-induced changes in the interparticle bridging
      reflect the slow nanoparticle motion measured by X-ray photon correlation
      spectroscopy. These results provide a first step for understanding how large
      shear can significantly affect the segmental motion in nanocomposites and open up
      new opportunities for designing mechanically responsive soft materials.

PMID- 29034931
TI  - Spontaneous symmetry breaking induced unidirectional rotation of a chain-grafted
      colloidal particle in the active bath.
AB  - Exploiting the energy of randomly moving active agents such as bacteria is a
      fascinating way to power a microdevice. Here we show, by simulations, that a
      chain-grafted disk-like colloidal particle can rotate unidirectionally and hence
      output work when immersed in a thin film of active particle suspension. The
      collective spontaneous symmetry breaking of chain configurations is the origin of
      the unidirectional rotation. Long persistence time, large propelling force and/or
      small rotating friction are keys to sustaining the collective broken symmetry and
      realizing the rotation. In the rotating state, we find very simple linear
      relations, e.g. between the mean angular speed and the propelling force. The time
      evolving asymmetry of chain configurations reveals that there are two types of
      non-rotating state. The basic phenomena are also observed in the macroscopic
      granular experiments, implying the generic nature of these phenomena. Our
      findings provide new insights into the collective spontaneous symmetry breaking
      in active systems with flexible objects and also open the way to conceive new
      soft/deformable microdevices.

PMID- 29034932
TI  - Design and development of multifunctional polyphosphoester-based nanoparticles
      for ultrahigh paclitaxel dual loading.
AB  - Multifunctional polyphosphoester-based nanoparticles capable of loading
      paclitaxel (PTX) both chemically and physically were prepared, achieving an
      ultrahigh equivalent PTX aqueous concentration of 25.30 mg mL-1. The dual-loaded
      nanoparticles were effective in killing cancer cells, which has the potential to
      minimize the amount of nanocarriers needed for clinical applications, due to
      their ultrahigh loading capacity.

PMID- 29034933
TI  - Isostaticity and the solidification of semiflexible polymer melts.
AB  - Using molecular dynamics simulations of a tangent-soft-sphere bead-spring polymer
      model, we examine the degree to which semiflexible polymer melts solidify at
      isostaticity. Flexible and stiff chains crystallize when they are isostatic as
      defined by appropriate degree-of-freedom-counting arguments. Semiflexible chains
      also solidify when isostatic if a generalized isostaticity criterion that
      accounts for the slow freezing out of configurational freedom as chain stiffness
      increases is employed. The configurational freedom associated with bond angles
      (theta) can be associated with the characteristic ratio Cinfinity = (1 +
      <cos(theta)>)/(1 - <cos(theta)>). We find that the dependence of the average
      coordination number at solidification [Z(Ts)] on chains' characteristic ratio
      Cinfinity has the same functional form [Z ? a - b ln(Cinfinity)] as the
      dependence of the average coordination number at jamming [Z(phiJ)] on Cinfinity
      in athermal systems, suggesting that jamming-related phenomena play a significant
      role in thermal polymer solidification.

PMID- 29034934
TI  - Complex coacervates based on recombinant mussel adhesive proteins: their
      characterization and applications.
AB  - Complex coacervates are a dense liquid phase of oppositely charged polyions
      formed by the associative separation of a mixture of polyions. Coacervates have
      been widely employed in many fields including the pharmaceutical, cosmetic, and
      food industries due to their intriguing interfacial and bulk material properties.
      More recently, attempts to develop an effective underwater adhesive have been
      made using complex coacervates that are based on recombinant mussel adhesive
      proteins (MAPs) due to the water immiscibility of complex coacervates and the
      adhesiveness of MAPs. MAP-based complex coacervates contribute to our
      understanding of the physical nature of complex coacervates and they provide a
      promising alternative to conventional invasive surgical repairs. Here, this
      review provides an overview of recombinant MAP-based complex coacervations, with
      an emphasis on their characterization and the uses of such materials for
      applications in the fields of biomedicine and tissue engineering.

PMID- 29034936
TI  - Synergistic antiviral effect of curcumin functionalized graphene oxide against
      respiratory syncytial virus infection.
AB  - The diseases attributable to viruses remain a global burden. The respiratory
      syncytial virus (RSV), which is considered as the major viral pathogen of the
      lower respiratory tract of infants, has been implicated in severe lung disease.
      In this contribution, we developed a beta-cyclodextrin (CD) functionalized
      graphene oxide (GO) composite, which displayed excellent antiviral activity and
      could load curcumin efficiently. RSV, a negative-sense single-stranded enveloped
      RNA virus, was employed as a model virus to investigate the antiviral activity of
      multifunctional GO. Proved by the tissue culture infectious dose assay and
      immunofluorescence assay, the curcumin loaded functional GO was confirmed with
      highly efficient inhibition for RSV infection and great biocompatibility to the
      host cells. The results showed that the composite could prevent RSV from
      infecting the host cells by directly inactivating the virus and inhibiting the
      viral attachment, and possessed prophylactic and therapeutic effects towards the
      virus. Our data indicate that the composite may provide new insights into
      antiviral therapy for RSV infection.

PMID- 29034935
TI  - Hedgehog-mesenchyme gene signature identifies bi-modal prognosis in luminal and
      basal breast cancer sub-types.
AB  - Hedgehog signaling (Hh) has been shown to be hyper-activated in several cancers.
      However, active Hh signaling can promote or inhibit tumor growth; thus
      identification of markers beyond main canonical Hh target genes is needed to
      improve patient selection and clinical outcome in response to Hh inhibitors.
      Cancer-associated fibroblasts (CAFs) have been linked with tumor progression and
      beneficial response to Hh inhibitors. Thus, we hypothesized that genes associated
      with Hh-activated CAFs can be used for stratification of tumors that will benefit
      from Hh inhibitors. In this work, we evaluated a 15-gene fingerprint that
      combines Hh and mesenchymal genes associated with CAF phenotype to profile breast
      cancer sub-types based on gene expression patterns among clustered groups. About
      3800 cancer samples were evaluated using random forest models and linear
      discriminant analysis to sort breast cancer by subtypes and therapeutic approach.
      The results showed that the Hh-mesenchyme gene fingerprint has a highly sensitive
      and differential expression pattern among basal and luminal A sub-groups. Basal
      samples with high levels of Hh target genes had better prognosis than luminal A
      samples. Luminal A samples with a tendency towards Hh signaling suppression had
      higher overall and disease-free survival rates particularly if deprived of
      hormone therapy. Hh transcriptional repressor GLI3 and signaling activator SMO
      were the top 2 genes for discriminating among samples with active Hh signaling in
      human breast cancer subtypes and Hh-inhibitor resistant tumors. Caveolin-1
      (CAV1), a gene with low expression in CAFs, shows strong correlation with active
      Hh signaling and discrimination among survival curves in luminal A patients with
      active or inactive Hh signaling. Our data suggest that CAV1 is an important gene
      for monitoring Hh inhibition in tumors and support further stratification by
      hormone therapy status prior to use of Hh inhibitors.

PMID- 29034937
TI  - Hybrid particle-continuum simulations coupling Brownian dynamics and local
      dynamic density functional theory.
AB  - We present a multiscale hybrid particle-field scheme for the simulation of
      relaxation and diffusion behavior of soft condensed matter systems. It combines
      particle-based Brownian dynamics and field-based local dynamics in an adaptive
      sense such that particles can switch their level of resolution on the fly. The
      switching of resolution is controlled by a tuning function which can be chosen at
      will according to the geometry of the system. As an application, the hybrid
      scheme is used to study the kinetics of interfacial broadening of a polymer
      blend, and is validated by comparing the results to the predictions from pure
      Brownian dynamics and pure local dynamics calculations.

PMID- 29034938
TI  - Comparative density functional theory-density functional tight binding study of
      fullerene derivatives: effects due to fullerene size, addends, and crystallinity
      on band structure, charge transport and optical properties.
AB  - We present a systematic comparative density functional theory-density functional
      tight binding study of multiple derivatives of C60 and C70 with different
      addends, in molecular as well as solid state. In particular, effects due to
      fullerene size, type and number of addends, and of crystallinity on band
      structure, charge transport, and optical properties are investigated. These are
      important, in particular, for rational selection of fullerene derivatives as
      acceptor and electron transport layers in organic as well as planar inverted
      perovskite solar cells. We find that by the choice of type and number of addends,
      one can modulate the LUMO within 0.4 eV. Changes in the HOMO can reach 0.7 eV.
      Substituting C70 for C60 results in destabilization of the HOMO by about 0.1 eV
      for indene and quinodimethane addends and by a less significant amount for PCBM
      addends. The effect of C70-C60 substitution on the LUMO is of similar magnitude.
      A more significant change in HOMO-LUMO energy is seen for the aryl addends. On
      the other hand, all C70 based molecules have strong visible absorption. For most
      addends, the crystal packing leads to a stabilization of both the LUMO and HOMO
      by about ~0.2 and ~0.1 eV, respectively, vs. single molecules. When using bis
      addends, it is also possible to enhance the visible absorption. Electron and hole
      transport rates are computed to vary vastly depending on the addends chosen;
      specifically, we compute that indene and quimodimethane addends can enhance
      charge transport rates while the aryl addend is predicted to result in
      substantially smaller mobilities of electrons and holes, vs. PC60BM. Furthermore,
      the -CH2 and bisaddend addition can significantly enhance the charge transfer
      rates for the PCBM addend.

PMID- 29034939
TI  - Supramolecular medicine.

PMID- 29034940
TI  - Near-infrared light and pH-responsive Au@carbon/calcium phosphate nanoparticles
      for imaging and chemo-photothermal cancer therapy of cancer cells.
AB  - A simple, mild and reproducible synthetic route was developed to fabricate the
      multifunctional Au@carbon/calcium phosphate core-shell nanoparticles (Au@C/CaP
      NPs), which act as an efficient nanoplatform for pH/near-infrared (NIR) dual
      responsive drug delivery, X-ray computed tomography (CT) imaging and synergistic
      chemo-photothermal cancer therapy in vitro.

PMID- 29034941
TI  - Selective photocatalysis of lignin-inspired chemicals by integrating hybrid
      nanocatalysis in microfluidic reactors.
AB  - This tutorial review assesses the available and possible strategies for attaining
      higher selectivity and yield of value-added chemicals from lignin using
      nanocatalysts embedded in a photomicroreactor. The design of the
      photomicroreactor, the choice of photocatalysts and the techniques for assembling
      the catalysts in such confined spaces are crucial elements. Lignin, a predominant
      industrial byproduct and pollutant, has been recognized today as a rich reservoir
      for aromatic chemicals and a prominent resource. The conventional batch
      photocatalytic studies on lignin, often using dissolved lignin under alkaline
      conditions, often generates a wide range of valuable organic chemicals which find
      applications in the pharmaceutical, food processing, cosmetic and fine chemical
      industries. The role of photocatalysis in such lignin depolymerizations is
      questionable as the dissolution procedure initiates fragmentation of lignin prior
      to light exposure. The complexity of the lignin structure also impedes necessary
      and decisive information to understand the reaction mechanism during such
      reactions in batch photoreactors. Considering these facts, photocatalysis studies
      on lignin entail a thoughtful reevaluation and focus on understanding the role of
      photocatalysis in the product generation and authenticating the implicated
      reaction mechanisms. The development of a photocatalytic system for lignin
      depolymerization in a continuous microreactor is a superior approach for the
      generation of valuable products emanating from lignin depolymerization and the
      successful execution of such strategies can pave the way for the
      commercialization of bio-based chemicals.

PMID- 29034942
TI  - Guanidinium-based "molecular glues" for modulation of biomolecular functions.
AB  - Molecular adhesion based on multivalent interactions plays essential roles in
      various biological processes. Hence, "molecular glues" that can adhere to
      biomolecules may modulate biomolecular functions and therefore can be applied to
      therapeutics. This tutorial review describes design strategies for developing
      adhesive motifs for biomolecules based on multivalent interactions. We highlight
      a guanidinium ion-based salt-bridge as a key interaction for adhesion to
      biomolecules and discuss the application of molecular glues for manipulation of
      biomolecular assemblies, drug delivery systems, and modulation of biomolecular
      functions.

PMID- 29034943
TI  - Catalytic CO2 reduction to valuable chemicals using NiFe-based nanoclusters: a
      first-principles theoretical evaluation.
AB  - Converting CO2 into valuable chemicals and fuels is one of the most practical
      routes for reducing CO2 emissions while fossil fuels continue to dominate the
      energy sector. Noble-metal-free NiFe bimetal nanoparticles have shown good
      catalytic activity in CO2 conversion. Herein we theoretically evaluated the
      catalytic performance and possible mechanisms of NiFe-based nanoclusters for
      hydrogenating CO2 to form formic acid and CO through bicarbonate by using a
      periodic and self-consistent density functional theory (DFT) simulation. The
      theoretical results illustrated that NiFe nanoclusters could have good catalytic
      activity and selectivity for HCO3- reduction to formic acid and the possible
      pathway is that HCO3- preferred to react with adsorbed H atoms of H2 on NiFe
      alloy nanoclusters through the carbon atom site. Moreover, the NiFe alloy
      nanoclusters with the Fe atom exposed on the surface of the Ni cluster showed
      better performance with a lower energy barrier compared to that with Fe doped in
      the corner of the Ni cluster. However, the generation of CO from HCO3- reduction
      was shown to be neither thermodynamically nor kinetically favorable on NiFe alloy
      nanoclusters. Additionally, the simulation results also suggested that it was
      thermodynamically unfavorable for further hydrogenated reduction of formic acid
      to formaldehyde on NiFe alloy nanoclusters themselves as well as supported on
      graphene. In summary, a molecular-level insight of CO2 reduction to valuable
      products on NiFe nanoclusters is offered in this study, which may provide some
      useful information for guiding the design of NiFe-based catalytic materials for
      efficient CO2 conversion to useful fuels.

PMID- 29034944
TI  - Power of protein/tRNA functional assembly against aberrant aggregation.
AB  - Understanding the mechanisms of protein oligomerization and aggregation is a
      major concern for biotechnology and medical purposes. However, significant
      challenges remain in determining the mechanism of formation of these
      superstructures and the environmental factors that can precisely modulate them.
      Notably the role that a functional ligand plays in the process of protein
      aggregation is largely unexplored. We herein address these issues with an
      original flavin-dependent RNA methyltransferase (TrmFO) used as a protein model
      since this protein employs a complex set of cofactors and ligands for catalysis.
      Here, we show that TrmFO carries an unstable protein structure that can partially
      mis-unfold leading to either formation of irregular and nonfunctional soluble
      oligomers endowed with hyper-thermal stability or large amorphous aggregates in
      the presence of salts. Mutagenesis confirmed that this peculiarity is an
      intrinsic property of a polypeptide and it is independent of the flavin coenzyme.
      Structural characterization and kinetic studies identified several regions of the
      protein that enjoy conformational changes and more particularly pinpointed the N
      terminal subdomain as being a key element in the mechanisms of oligomerization
      and aggregation. Only stabilization of this region via tRNA suppresses these
      aberrant protein states. Although protein chaperones emerged as major actors
      against aggregation, our study emphasizes that other powerful mechanisms exist
      such as the stabilizing effect of functional assemblies that provide an
      additional layer of protection against the instability of the proteome.

PMID- 29034945
TI  - Quantum effect enhanced magnetism of C-doped phosphorene nanoribbons: first
      principles calculations.
AB  - Manipulating magnetism of low-dimensional materials is of great importance for
      their practical applications. Here, using first-principles calculations, we
      report a systematic investigation of the magnetic properties of C-doped H
      saturated zigzag phosphorene nanoribbons (H-ZPNRs), which are rather different
      from those of 2D periodic systems due to the quantum size effect. First of all,
      we observed a greatly enhanced magnetic moment locating mainly on the C atom and
      also slightly on its surrounding P atoms. Our results also indicated a strong
      dependence of the magnetic moment of the C atom on its location, which decays
      from the edge to the center site of the nanoribbons with an odd-even oscillating
      behavior originating from Friedel oscillation in low-dimensional materials. As
      for the C atom on a specific location, its magnetic moment decreases gradually
      with increasing width of H-ZPNRs, degenerating to the 2D case. What is more, we
      found that both the magnitude and the oscillating behavior of the magnetic moment
      on the C atom can be tuned by the edge saturation atoms. In addition, the case of
      two C atoms co-doping H-ZPNRs was also studied, showing non-magnetic (NM),
      ferromagnetic (FM) and antiferromagnetic (AFM) states depending on the locations
      of the two C atoms. Our findings suggest a plausible route for manipulating
      magnetism of the sp element doped H-ZPNRs, which are expected to have potential
      applications in spintronics.

PMID- 29034946
TI  - Spin labelling for integrative structure modelling: a case study of the
      polypyrimidine-tract binding protein 1 domains in complexes with short RNAs.
AB  - A combined method, employing NMR and EPR spectroscopies, has demonstrated its
      strength in solving structures of protein/RNA and other types of biomolecular
      complexes. This method works particularly well when the large biomolecular
      complex consists of a limited number of rigid building blocks, such as RNA
      binding protein domains (RBDs). A variety of spin labels is available for such
      studies, allowing for conventional as well as spectroscopically orthogonal double
      electron-electron resonance (DEER) measurements in EPR. In this work, we compare
      different types of nitroxide-based and Gd(iii)-based spin labels attached to
      isolated RBDs of the polypyrimidine-tract binding protein 1 (PTBP1) and to short
      RNA fragments. In particular, we demonstrate experiments on spectroscopically
      orthogonal labelled RBD/RNA complexes. For all experiments we analyse spin
      labelling, DEER method performance, resulting distance distributions, and their
      consistency with the predictions from the spin label rotamers analysis. This work
      provides a set of intra-domain calibration DEER data, which can serve as a basis
      to start structure determination of the full length PTBP1 complex with an RNA
      derived from encephalomycarditis virus (EMCV) internal ribosomal entry site
      (IRES). For a series of tested labelling sites, we discuss their particular
      advantages and drawbacks in such a structure determination approach.

PMID- 29034947
TI  - Revealing the electronic character of the positive electrode/electrolyte
      interface in lithium-ion batteries.
AB  - High voltage operating active materials are among the most promising components
      for positive electrodes of future high energy lithium-ion batteries. However, the
      operating potential range of such materials often exceeds anodically the
      thermodynamic stability window of the electrolyte. A surface layer is therefore
      formed, which is supposed to be one of the reasons for the high irreversible
      charge loss of these electrodes. The electronic character of such a surface layer
      formed at the electrode/electrolyte interface of LiNi0.5Mn1.5O4 (LNM),
      stoichiometric (x = 0) and overlithiated (x = 0.1) Li1+x(Ni1/3Mn1/3Co1/3)1-xO2
      (NMC) based paste electrodes was investigated in situ using feedback-mode
      scanning electrochemical microscopy (SECM). The role in the formation of an
      electronically insulating layer of a conductive carbon additive-based electrode
      and of the Al current collector was explored as well. The surface layers formed
      on all oxide based paste electrodes and on conductive carbon additive based
      electrodes showed unexpectedly an electronic conducting behavior, while the Al
      current collector formed an electronically insulating layer which was found to be
      influenced by the electrolyte.

PMID- 29034948
TI  - Bandgap engineering by cationic disorder: case study on AgBiS2.
AB  - The influence of cationic disorder on the electronic structure of ternary
      compounds, here exemplified on AgBiS2 material, is studied by means of accurate
      first principles periodic density functional theory based calculations. For
      AgBiS2 cationic disorder in going from semiconducting matildite to a metallic
      arrangement crystal structure is found to induce a significant decrease in the
      band gap, as a result of cation-disorder conduction band tail states penetrating
      into the matildite bandgap. Properly aligned conduction band minimum and valence
      band maximum show that cationic disorders lead to a noticeable drop of the former
      and a slight increase of the latter. The present results indicate that
      temperature effects triggering cationic disorder will have a beneficial effect on
      the photoactivity of AgBiS2 samples provided that the metallic limit is not
      reached.

PMID- 29034949
TI  - A multidonor-photosensitizer-multiacceptor triad for long-lived directional
      charge separation.
AB  - The modular assembly of a directional photoredox-active multidonor
      photosensitizer-multiacceptor (Dn-P-Am) architecture is presented. The triad
      assembly features a central Ru(ii) sensitizer equipped with pendant polymer
      chains consisting of multiple triarylamine (pTARA) and naphthalene diimide (pNDI)
      units, respectively. Upon excitation, the efficient formation (>96%) of charge
      separation (CS) was observed featuring similar CS lifetimes (400 ns) as related
      molecular triads. In contrast, a significant additional longer-lived CS component
      (2400 ns, 30%) is observed indicating multiple contributing pathways.

PMID- 29034950
TI  - Spectroscopic characteristics of Rubricoccus marinus xenorhodopsin (RmXeR) and a
      putative model for its inward H+ transport mechanism.
AB  - A new group of microbial rhodopsins named xenorhodopsins (XeR), which are closely
      related to the cyanobacterial Anabaena sensory rhodopsin, show a light-driven
      "inward" proton transport activity, as reported for one representative of this
      group from Parvularcula oceani (PoXeR). In this study, we functionally and
      spectroscopically characterized a new member of the XeR clade from a marine
      bacterium Rubricoccus marinus SG-29T (RmXeR). Escherichia coli cells expressing
      recombinant RmXeR showed a light-induced alkalization of the cell suspension,
      which was strongly impaired by a protonophore, suggesting that RmXeR is a light
      driven "inward" proton pump as is PoXeR. The spectroscopic properties of purified
      RmXeR were investigated and compared with those of PoXeR and a light-driven
      "outward" proton pump, bacteriorhodopsin (BR) from the archaeon Halobacterium
      salinarum. Action spectroscopy revealed that RmXeR with all-trans retinal is
      responsible for the light-driven inward proton transport activity, but not with
      13-cis retinal. From pH titration experiments and mutational analysis, we
      estimated the pKa values for the protonated Schiff base of the retinal
      chromophore and its counterion as 11.1 +/- 0.07 and 2.1 +/- 0.07, respectively.
      Of note, the direction of both the retinal composition change upon light-dark
      adaptation and the acid-induced spectral shift was opposite that of BR, which is
      presumably related to the opposite directions of ion transport (from outside to
      inside for RmXeR and from inside to outside for BR). Flash photolysis experiments
      revealed the appearances of three intermediates (L, M and O) during the
      photocycle. The proton uptake and release were coincident with the formation and
      decay of the M intermediate, respectively. Together with associated findings from
      other microbial rhodopsins, we propose a putative model for the inward proton
      transport mechanism of RmXeR.

PMID- 29034952
TI  - Viscum articulatum Burm. f.: a review on its phytochemistry, pharmacology and
      traditional uses.
AB  - OBJECTIVES: The aim of this study was to review and highlight traditional and
      ethnobotanical uses, phytochemical constituents, IP status, biological activity
      and pharmacological activity of Viscum articulatum. METHODS: Thorough literature
      searches were performed on Viscum articulatum, and data were analysed for
      reported traditional uses, pharmacological activity, phytochemicals present and
      patents filed. Scientific and patent databases such as PubMed, Science Direct,
      Google Scholar, Google patents, USPTO and Espacenet were searched using different
      keywords. KEY FINDINGS: Viscum articulatum has been traditionally used in
      different parts of the world for treatment of various ailments. Almost all the
      parts such as leaves, root, stem and bark are having medicinal values and are
      reported for their uses in Ayurvedic and Chinese system of medicine for the
      management of various diseases. Modern scientific studies demonstrate efficacy of
      this plant against hypertension, ulcer, epilepsy, inflammation, wound,
      nephrotoxicity, HIV, cancer, etc. Major bioactive phytochemicals include
      oleanolic acid, betulinic acid, eriodictyol, naringenin, beta-amyrin acetate,
      visartisides, etc. CONCLUSIONS: Side effects of allopathic medicines have created
      a global opportunity, acceptance and demand for phytomedicines. Viscum
      articulatum could be an excellent source of effective and safe phytomedicine for
      various ailments if focused translational efforts are undertaken by integrating
      the existing outcomes of researches.

PMID- 29034951
TI  - A nanocrystal-based formulation improves the pharmacokinetic performance and
      therapeutic response of albendazole in dogs.
AB  - OBJECTIVES: Here, we aimed to assess the pharmacokinetic performance and
      therapeutic response (anthelmintic efficacy) of an albendazole (ABZ) nano-sized
      formulation in dogs. METHODS: In the pharmacokinetic study, ABZ self-dispersible
      nanocrystals (SDNCS) and a control formulation were administered orally to
      healthy dogs (n = 6). The concentrations of the sulphoxide metabolite in plasma
      were determined by high-performance liquid chromatography. For the anthelmintic
      efficacy trial, SDNCS and a commercially available formulation of ABZ were given
      to naturally parasitised dogs. The number of Ancylostoma caninum eggs in the
      faeces was determined using the McMaster technique. KEY FINDINGS: The area under
      the curve, Tmax and Cmax for the SDNCS were improved compared to the control. The
      efficacy study showed no statistical differences between the SDNCS and the
      commercial formulation at the doses of 25 and 12.5 mg/kg. However, significant
      differences (P < 0.05) between the treatments were found at 6.25 mg/kg (a quarter
      of the reference dose) with a reduction in the faecal nematode egg counts of 62.0
      +/- 21.1% and 100 +/- 0% for the control and SDNCS, respectively. CONCLUSIONS:
      The improved pharmacokinetic performance observed for the novel formulation of
      ABZ correlated with an improved in vivo therapeutic response against a model
      intestinal nematode parasite in dogs.

PMID- 29034953
TI  - Reproductive autonomy of women and girls under the Convention on the Rights of
      Persons with Disabilities.
AB  - Women and girls with disabilities have historically been denied the freedom to
      make their own choices in matters relating to their reproduction. In the
      healthcare sector they experience multiple discriminatory practices. Women and
      girls with intellectual disabilities are particularly vulnerable to coerced or
      forced medical interventions. The present article considers the contribution the
      Convention on the Rights of Persons with Disabilities makes towards affirming the
      rights of women and girls with disabilities to enjoy reproductive autonomy,
      including autonomy related to reproductive health, on an equal basis with
      individuals without disabilities. The Convention is paradigm-setting in its
      maximal approach to affirming the rights of individuals with disabilities to make
      autonomous choices under conditions of equality and non-discrimination. The
      Convention is the first human rights treaty to clearly affirm that impairment of
      decision-making skills is not a justification for depriving a person with
      cognitive or intellectual disability of legal capacity.

PMID- 29034955
TI  - A review of issues of nomenclature and taxonomy of Hypericum perforatum L. and
      Kew's Medicinal Plant Names Services.
AB  - OBJECTIVES: To review which names are used to refer to Hypericum perforatum L. in
      health regulation and medicinal plant references, and the potential for ambiguity
      or imprecision. KEY FINDINGS: Structured searches of Kew's Medicinal Plant Names
      Services Resource, supplemented with other online bibliographic resources, found
      that the scientific name Hypericum perforatum L. is used consistently in the
      literature, but variation between subspecies is rarely considered by researchers.
      Research is still published using only the common name 'St John's wort' despite
      it being imprecise; at least 80 other common names are also used for this plant
      in multiple languages. SUMMARY: Ambiguous and alternative plant names can lead to
      ineffective regulation, misinterpretation of literature, substitution of raw
      material or the failure to locate all published research. Kew's Medicinal Plant
      Names Services (MPNS) maps all names used for each plant in medicinal plant
      references onto current taxonomy, thereby providing for disambiguation and
      comprehensive access to the regulations and references that cite that plant,
      regardless of the name used. MPNS also supplies the controlled vocabulary for
      plant names now required for compliance with a new standard (Identification of
      Medicinal Products, IDMP) adopted by medicines regulators worldwide.

PMID- 29034954
TI  - Intergenerational environmental effects: functional signals in offspring
      transcriptomes and metabolomes after parental jasmonic acid treatment in
      apomictic dandelion.
AB  - Parental environments can influence offspring traits. However, the magnitude of
      the impact of parental environments on offspring molecular phenotypes is poorly
      understood. Here, we test the direct effects and intergenerational effects of
      jasmonic acid (JA) treatment, which is involved in herbivory-induced defense
      signaling, on transcriptomes and metabolomes in apomictic common dandelion
      (Taraxacum officinale). In a full factorial crossed design with parental and
      offspring JA and control treatments, we performed leaf RNA-seq gene expression
      analysis, LC-MS metabolomics and total phenolics assays in offspring plants.
      Expression analysis, leveraged by a de novo assembled transcriptome, revealed an
      induced response to JA exposure that is consistent with known JA effects. The
      intergenerational effect of treatment was considerable: 307 of 858 detected JA
      responsive transcripts were affected by parental JA treatment. In terms of the
      numbers of metabolites affected, the magnitude of the chemical response to
      parental JA exposure was c. 10% of the direct JA treatment response.
      Transcriptome and metabolome analyses both identified the phosphatidylinositol
      signaling pathway as a target of intergenerational JA effects. Our results
      highlight that parental environments can have substantial effects in offspring
      generations. Transcriptome and metabolome assays provide a basis for zooming in
      on the potential mechanisms of inherited JA effects.

PMID- 29034956
TI  - Homoeologous exchanges cause extensive dosage-dependent gene expression changes
      in an allopolyploid crop.
AB  - Structural variation is a major source of genetic diversity and an important
      substrate for selection. In allopolyploids, homoeologous exchanges (i.e. between
      the constituent subgenomes) are a very frequent type of structural variant.
      However, their direct impact on gene content and gene expression had not been
      determined. Here, we used a tissue-specific mRNA-Seq dataset to measure the
      consequences of homoeologous exchanges (HE) on gene expression in Brassica napus,
      a representative allotetraploid crop. We demonstrate that expression changes are
      proportional to the change in gene copy number triggered by the HEs. Thus, when
      homoeologous gene pairs have unbalanced transcriptional contributions before the
      HE, duplication of one copy does not accurately compensate for loss of the other
      and combined homoeologue expression also changes. These effects are, however,
      mitigated over time. This study sheds light on the origins, timing and functional
      consequences of homeologous exchanges in allopolyploids. It demonstrates that the
      interplay between new structural variation and the resulting impacts on gene
      expression, influences allopolyploid genome evolution.

PMID- 29034957
TI  - A root-knot nematode small glycine and cysteine-rich secreted effector, MiSGCR1,
      is involved in plant parasitism.
AB  - Root-knot nematodes, Meloidogyne spp., are obligate endoparasites that maintain a
      biotrophic relationship with their hosts. They infect roots as microscopic
      vermiform second-stage juveniles, and establish specialized feeding structures
      called 'giant-cells', from which they withdraw water and nutrients. The nematode
      effector proteins secreted in planta are key elements in the molecular dialogue
      of parasitism. Here, we compared Illumina RNA-seq transcriptomes for M. incognita
      obtained at various points in the lifecycle, and identified 31 genes more
      strongly expressed in parasitic stages than in preparasitic juveniles. We then
      selected candidate effectors for functional characterization. Quantitative real
      time PCR and in situ hybridizations showed that the validated differentially
      expressed genes are predominantly specifically expressed in oesophageal glands of
      the nematode. We also soaked the nematodes in siRNA to silence these genes and to
      determine their role in pathogenicity. The silencing of the dorsal gland specific
      Minc18876 and its paralogues resulted in a significant, reproducible decrease in
      the number of mature females with egg masses, demonstrating a potentially
      important role for the small glycine- and cysteine-rich effector MiSGCR1 in early
      stages of plant-nematode interaction. Finally, we report that MiSGCR1 suppresses
      plant cell death induced by bacterial or oomycete triggers of plant defense.

PMID- 29034958
TI  - Energy: A concept analysis from a nursing perspective.
AB  - The term "energy" is common in day-to-day language and denotes a myriad of
      different meanings depending on context. Energy is one of the most significant
      concepts for nearly all of the sciences including nursing, and yet it continues
      to be ambiguously defined. This article utilizes a modified version of Walker and
      Avant's framework for concept analysis (2011) to identify the characteristics,
      attributes, and antecedents of the concept of energy and provides a practical and
      theoretical application to nursing. The defining attributes discussed are power,
      productivity, effort, and activity. Model and contrary cases are presented to
      better provide a representation of the concept of energy. Empirical referents or
      a proper measurement or assessment of energy are nonspecific and poorly defined.
      Opportunities for future research related to the concept of energy in nursing
      include implementation of new terminology or theory development.

PMID- 29034960
TI  - Celebrating Baer - a Nordic scientist who discovered the mammalian oocyte.

PMID- 29034959
TI  - Quantitative proteomics of a B12 -dependent alga grown in coculture with bacteria
      reveals metabolic tradeoffs required for mutualism.
AB  - The unicellular green alga Lobomonas rostrata requires an external supply of
      vitamin B12 (cobalamin) for growth, which it can obtain in stable laboratory
      cultures from the soil bacterium Mesorhizobium loti in exchange for
      photosynthate. We investigated changes in protein expression in the alga that
      allow it to engage in this mutualism. We used quantitative isobaric tagging
      (iTRAQ) proteomics to determine the L. rostrata proteome grown axenically with
      B12 supplementation or in coculture with M. loti. Data are available via
      ProteomeXchange (PXD005046). Using the related Chlamydomonas reinhardtii as a
      reference genome, 588 algal proteins could be identified. Enzymes of amino acid
      biosynthesis were higher in coculture than in axenic culture, and this was
      reflected in increased amounts of total cellular protein and several free amino
      acids. A number of heat shock proteins were also elevated. Conversely,
      photosynthetic proteins and those of chloroplast protein synthesis were
      significantly lower in L. rostrata cells in coculture. These observations were
      confirmed by measurement of electron transfer rates in cells grown under the two
      conditions. The results indicate that, despite the stability of the mutualism, L.
      rostrata experiences stress in coculture with M. loti, and must adjust its
      metabolism accordingly.

PMID- 29034961
TI  - A randomized trial of automated intermittent ropivacaine administration vs.
      continuous infusion in an interscalene catheter.
AB  - BACKGROUND: Ultrasound-guided interscalene nerve block with ropivacaine as local
      anesthetic agent given as boluses or continuous infusion is the preferred pain
      management after major shoulder surgery. The use of automated intermittent
      boluses has been shown to be superior to continuous infusion in sciatic and
      epidural nerve block. HYPOTHESIS: Automated intermittent boluses reduce pain
      after major shoulder surgery. METHODS: Seventy patients aged 18-75 years,
      scheduled for major shoulder surgery under general anesthesia with interscalene
      nerve block were included in this randomized controlled trial. Patients were
      allocated to either automated intermittent boluses with 16 mg ropivacaine every 2
      h combined with patient-controlled administration or to a conventional regimen of
      continuous infusion of 8 mg/h (4 ml/h) of ropivacaine combined with patient
      controlled administration (2 ml, lockout time 30 min). Pain (Visual Analog Scale,
      VAS) was assessed every 8 h postoperatively. RESULTS: Fifty-seven patients
      completed the study, 29 in the continuous infusion group and 28 in the automated
      intermittent bolus group. Shoulder arthroplasty was performed in 49 (86%) of the
      cases. There were no significant differences in VAS score from 8 to 48 h post
      operatively. No significant difference in opioid usage was observed. The
      automated intermittent bolus group reported significantly less force on coughing
      and more hoarseness. A significantly lower volume of ropivacaine was used in the
      automated intermittent bolus group. CONCLUSION: Automated intermittent boluses
      did not reduce pain or rescue opioid consumption compared with continuous
      infusion of ropivacaine. The automated intermittent bolus group had significantly
      less force on coughing and more hoarseness.

PMID- 29034962
TI  - Analysis and evaluation of the moral distress theory.
AB  - Moral distress is a pervasive problem in nursing resulting in a detriment to
      patient care, providers, and organizations. Over a decade ago, the moral distress
      theory (MDT) was proposed and utilized in multiple research studies. This middle
      range theory explains and predicts the distress that occurs in a nurse because of
      moral conflict. The research findings born from this theory have been
      substantial. Since inception of this theory, moral distress has been extensively
      examined which has further elaborated its understanding. This paper provides an
      analysis and evaluation of the MDT according to applicable guidelines. Current
      understanding of the phenomenon indicates that a new theory may be warranted to
      better predict, treat, and manage moral distress.

PMID- 29034963
TI  - Does the Effect of Justice System Attitudes on Adolescent Crime Vary Based on
      Psychosocial Maturity?
AB  - Adolescents who view the justice system negatively are prone to commit crime.
      Simultaneously, youth who have difficulty regulating their behavior are likely to
      commit crime. Using a longitudinal sample of 1,216 male adolescents (ages 13-17)
      who had been arrested for the first time, were racially/ethnically diverse, and
      were drawn from three U.S. states, this study incorporated a developmental
      perspective into the procedural justice framework to examine whether psychosocial
      immaturity moderated the effect of justice system attitudes on youth crime.
      Attitudes toward the justice system were associated with reoffending among
      psychosocially mature youth, but not among psychosocially immature youth. This
      developmental perspective indicates that psychosocially immature youth who have
      difficulty regulating their behavior may be at risk of engaging in crime
      regardless of how they perceive the justice system.

PMID- 29034964
TI  - Hemispheric asymmetry of the frontolimbic cortex in young adults with borderline
      personality disorder.
AB  - OBJECTIVE: Although the frontolimbic cortex has been implicated in borderline
      personality disorder (BPD), information about possible asymmetries in this region
      in patients with BPD is limited. This study aimed to examine whether frontolimbic
      cortex asymmetries differ between patients with BPD and healthy individuals.
      METHODS: The brains of 30 young adult patients with BPD and 32 healthy control
      subjects were scanned with magnetic resonance imaging (MRI). The participants
      completed self-report scales assessing impulsivity, affect intensity and other
      psychological variables. Gray matter volume, surface area, and cortical thickness
      in regions of interest (ROIs), namely anterior insula (AI) and anterior cingulate
      cortex (ACC) were determined and the data were probed for hemisphere-group
      interactions. RESULTS: Relative to controls, patients with BPD had reduced
      cortical thickness in left ACC and less surface area and gray matter volume in
      left AI. Significant group-hemisphere interactions were observed for gray matter
      volume and surface area of AI and for cortical thickness of ACC. Post hoc
      analysis showed that the BPD patients had greater frontolimbic cortex asymmetry
      than healthy controls; furthermore, greater asymmetry of AI&ACC correlated with a
      higher score in attention subscale of Barratt Impulsiveness Scale. CONCLUSION:
      Patients with BPD have greater frontolimbic asymmetry than healthy individuals.

PMID- 29034965
TI  - Role of serum albumin as a nanoparticulate carrier for nose-to-brain delivery of
      R-flurbiprofen: implications for the treatment of Alzheimer's disease.
AB  - OBJECTIVES: R-flurbiprofen (R-FP) was found to offer neuroprotective effects by
      inhibiting mitochondrial calcium overload induced by beta-amyloid peptide
      toxicity in Alzheimer's disease (AD). However, poor brain penetration after oral
      administration posed a challenge to its further development for AD treatment. In
      this study, we investigated the potential of serum albumin as nanoparticulate
      carriers for nose-to-brain delivery of R-FP to improve its brain accumulation.
      METHODS: Mice were subjected to three treatment groups: (1) intranasal R-FP
      solution, (2) oral R-FP solution and (3) intranasal R-FP albumin nanoparticles.
      We also investigated whether the in-vivo R-FP level achieved in the brain
      afforded by intranasal administration of R-FP nanoparticles had any effect on
      mitochondrial respiratory activity in an in-vitro AD model. KEY FINDINGS: Our in
      vivo experiments demonstrate that the intranasal administration of serum albumin
      based R-FP nanoparticles achieved higher brain-to-plasma ratio profile as
      compared to intranasal and oral administration of a simple R-FP solution. We
      observed significantly improved basal and maximal mitochondrial respiration in
      cells treated with R-FP albumin nanoparticles at in-vivo brain concentration.
      CONCLUSIONS: Serum albumin-based nanoparticles administered via the nasal route
      may be a viable approach in delivering therapeutic agents to the brain to
      alleviate mitochondrial dysfunction in AD.

PMID- 29034967
TI  - Evaluation of a method for isocapnic hyperventilation: a clinical pilot trial.
AB  - BACKGROUND: Isocapnic hyperventilation (IHV) is a method that shortens time to
      extubation after inhalation anaesthesia using hyperventilation (HV) without
      lowering airway CO2 . In a clinical trial on patients undergoing long-duration
      sevoflurane anaesthesia for major ear-nose-throat (ENT) surgery, we evaluated the
      utility of a technique for CO2 delivery (DCO2 ) to the inspiratory limb of a
      closed breathing circuit, during HV, to achieve isocapnia. METHODS: Fifteen adult
      ASA 1-3 patients were included. After end of surgery, mechanical HV was started
      by doubling baseline minute ventilation. Simultaneously, CO2 was delivered and
      dosed using a nomogram developed in a previous experimental study. Time to
      extubation and eye opening was recorded. Inspired (FICO2 ) and expired (FETCO2 )
      CO2 and arterial CO2 levels were monitored during IHV. Cognition was tested pre
      operatively and at 20, 40 and 60 min after surgery. RESULTS: A DCO2 of 285 +/- 45
      ml/min provided stable isocapnia during HV (13.5 +/- 4.1 l/min). The
      corresponding FICO2 level was 3.0 +/- 0.3%. Time from turning off the vaporizer
      (1.3 +/- 0.1 MACage) to extubation (0.2 +/- 0.1 MACage) was 11.3 +/- 1.8 min
      after 342 +/- 131 min of anaesthesia. PaCO2 and FETCO2 remained at normal levels
      during and after IHV. In 85% of the patients, post-operative cognition returned
      to pre-operative values within 60 min. CONCLUSIONS: In this cohort of patients, a
      DCO2 nomogram for IHV was validated. The patients were safely extubated shortly
      after discontinuing long-term sevoflurane anaesthesia. Perioperatively, there
      were no adverse effects on arterial blood gases or post-operative cognition. This
      technique for IHV can potentially be used to decrease emergence time from
      inhalation anaesthesia.

PMID- 29034966
TI  - Influence of sulfate supply on selenium uptake dynamics and expression of
      sulfate/selenate transporters in selenium hyperaccumulator and
      nonhyperaccumulator Brassicaceae.
AB  - Stanleya pinnata not only hyperaccumulates selenium (Se) to 0.5% of its dry
      weight, but also exhibits higher tissue Se-to-sulfur (S) ratios than other
      species and its surroundings. To investigate the mechanisms underlying this Se
      enrichment, we compared S. pinnata with the nonhyperaccumulators S. elata and
      Brassica juncea for selenate uptake in long- (9 d) and short-term (1 h) assays,
      using different concentrations of selenate and competitor sulfate. Different
      sulfate pre-treatments (0, 0.5, 5 mM, 3 d) were also tested for effects on
      selenate uptake and sulfate transporters' expression. Relative to
      nonhyperaccumulators, S. pinnata showed higher rates of root and shoot Se
      accumulation and less competitive inhibition by sulfate or by high-S
      pretreatment. The selenate uptake rate for S. pinnata (1 h) was three- to four
      fold higher than for nonhyperaccumulators, and not significantly affected by 100
      fold excess sulfate, which reduced selenate uptake by 100% in S. elata and 40% in
      B. juncea. Real-time reverse transcription PCR indicated constitutive
      upregulation in S. pinnata of sulfate transporters SULTR1;2 (root influx) and
      SULTR2;1 (translocation), but reduced SULTR1;1 expression (root influx). In S.
      pinnata, selenate uptake and translocation rates are constitutively elevated and
      relatively sulfate-independent. Underlying mechanisms likely include
      overexpression of SULTR1;2 and SULTR2;1, which may additionally have evolved
      enhanced specificity for selenate over sulfate.

PMID- 29034968
TI  - Genetics and evolution of MIXTA genes regulating cotton lint fiber development.
AB  - Cotton, with cellulose-enriched mature fibers, is the largest source of natural
      textiles. Through a map-based cloning strategy, we isolated an industrially
      important lint fiber development gene (Li3 ) that encodes an MYB-MIXTA-like
      transcription factor (MML) on chromosome D12 (GhMML4_D12). Virus-induced gene
      silencing or decreasing the expression of the GhMML4_D12 gene in n2 NSM plants
      resulted in a significant reduction in epidermal cell prominence and lint fiber
      production. GhMML4_D12 is arranged in tandem with GhMML3, another MIXTA gene
      responsible for fuzz fiber development. These two very closely related MIXTA
      genes direct fiber initiation production in two specialized cell forms: lint and
      fuzz fibers. They may control the same metabolic pathways in different cell
      types. The MIXTAs expanded in Malvaceae during their evolution and produced a
      Malvaceae-specific family that regulates epidermal cell differentiation,
      different from the gene family that regulates leaf hair trichome development.
      Cotton has developed a unique transcriptional regulatory network for fiber
      development. Characterization of target genes regulating fiber production has
      provided insights into the molecular mechanisms underlying cotton fiber
      development and has allowed the use of genetic engineering to increase lint yield
      by inducing more epidermal cells to develop into lint rather than fuzz fibers.

PMID- 29034969
TI  - Experience with MAD on children with epilepsy in Egypt after classic KD failure.
AB  - BACKGROUND AND AIM: Modified Atkins diet (MAD) is a less restrictive type of
      ketogenic diet (KD) as compared to the classic one. The aim of this study was to
      evaluate the impact of 9 months MAD treatment on the growth and seizure control
      in patients with intractable epilepsy as well as the quality of life (QoL) of
      their mothers. SUBJECTS AND METHODS: The study included 15 patients with
      intractable epilepsy who could not tolerate their classic KD management plan.
      From the 15 recruited cases, only seven patients completed this nine months
      prospective study. After neurological reassessment, the patients were prescribed
      MAD tailored from the local Egyptian ingredients. Arabic translation of the WHO
      Quality of life Instruments (WHOQOL-BREF) scale was calculated for the mothers
      initially and 9 months later. Daily seizure frequency with severity assessment by
      Chalfont scale was recorded as well as monthly weight and length throughout the
      study period. RESULTS: Mothers 'QoL in all WHOQOL-BREF domains significantly
      improved (P < .001) after nine months follow-up coupled by significant decrease
      in Chalfont scores from 51.00 +/- 15.45 to 20.57 +/- 21.45 and daily seizure
      frequency from 13.29 +/- 6.99 to 2.71 +/- 3.68. Regarding anthropometric data,
      there was significant increase in patients' weight and length as well as in the z
      score for weight and length. CONCLUSION: After nine months of MAD, growth and
      seizure parameters significantly improved in the intractable epilepsy patients as
      well as their mothers& QoL. We thus recommend MAD as a more flexible alternative
      in intractable epilepsy patients who can not tolerate classic KD.

PMID- 29034970
TI  - Oral health of older residents in care and community dwellers: nursing
      implications.
AB  - BACKGROUND: Poor oral health is associated with a reduced quality of life and
      serious illnesses. Consequently, nurses need to be more aware of oral health to
      improve the general health of residents in care. AIM: To evaluate and compare
      oral health behaviours and levels of salivary haemoglobin and dental biofilm
      acidogenicity, which can be used to evaluate oral disease activity, between
      residents and community dwellers in South Korea. METHODS: This cross-sectional
      study included 133 participants: 64 residents and 69 community dwellers. All
      participants completed a questionnaire and tests to measure their salivary
      haemoglobin and dental biofilm acidogenicity. RESULTS: A higher percentage of
      community dwellers than of residents brushed their teeth three times a day,
      cleaned their tongue, used interdental cleaning devices and had visited a dental
      clinic within 1 year. The levels of salivary haemoglobin and dental biofilm
      acidogenicity tended to be higher in residents than in community dwellers.
      CONCLUSION: Residents showed poorer oral health behaviours and higher levels of
      gingival bleeding and acid production by oral bacteria than did community
      dwellers. IMPLICATIONS FOR NURSING PRACTICE: Nursing staff should enhance their
      monitoring of oral hygiene status and provide quality oral care to residents
      through cooperation with dental professionals. IMPLICATIONS FOR NURSING AND
      HEALTH POLICY: Policymakers should be aware that oral health is an essential
      component of improving general health and well-being and therefore strive to
      develop policies to promote oral care services provided to residents. Nursing
      policies, such as mandating oral care and hands-on training in oral care for
      nursing staff, are important. We also suggest that factors related to oral care
      be added to the establishment or accreditation standards of care facilities.

PMID- 29034971
TI  - Belinda E. Medlyn.

PMID- 29034972
TI  - Corrigendum.

PMID- 29034973
TI  - Biocrust ecology: unifying micro- and macro-scales to confront global change.

PMID- 29034974
TI  - Conifer tree-ring density inter-annual variability - anatomical, physiological
      and environmental determinants.

PMID- 29034976
TI  - Corrigendum.

PMID- 29034975
TI  - New insights into plant-microbe interactions through advances in fungal genetics.

PMID- 29034977
TI  - Antisense movement on the clock.

PMID- 29034978
TI  - Arbuscular mycorrhizal fungi promote coexistence and niche divergence of
      sympatric palm species on a remote oceanic island.
AB  - Microbes can have profound effects on their hosts, driving natural selection,
      promoting speciation and determining species distributions. However, soil
      dwelling microbes are rarely investigated as drivers of evolutionary change in
      plants. We used metabarcoding and experimental manipulation of soil microbiomes
      to investigate the impact of soil and root microbes in a well-known case of
      sympatric speciation, the Howea palms of Lord Howe Island (Australia). Whereas H.
      forsteriana can grow on both calcareous and volcanic soils, H. belmoreana is
      restricted to, but more successful on, volcanic soil, indicating a trade-off in
      adaptation to the two soil types. We suggest a novel explanation for this trade
      off. Arbuscular mycorrhizal fungi (AMF) are significantly depleted in H.
      forsteriana on volcanic soil, relative to both H. belmoreana on volcanic soil and
      H. forsteriana on calcareous soil. This is mirrored by the results of survival
      experiments, where the sterilization of natural soil reduces Howea fitness in
      every soil-species combination except H. forsteriana on volcanic soil.
      Furthermore, AMF-associated genes exhibit evidence of divergent selection between
      Howea species. These results show a mechanism by which divergent adaptation can
      have knock-on effects on host-microbe interactions, thereby reducing
      interspecific competition and promoting the coexistence of plant sister species.

PMID- 29034980
TI  - Geometric Design of Scalable Forward Scatterers for Optimally Efficient Solar
      Transformers.
AB  - It will be ideal to deliver equal, optimally efficient "doses" of sunlight to all
      cells in a photobioreactor system, while simultaneously utilizing the entire
      solar resource. Backed by the numerical scattering simulation and optimization,
      here, the design, synthesis, and characterization of the synthetic iridocytes
      that recapitulated the salient forward-scattering behavior of the Tridacnid clam
      system are reported, which presents the first geometric solution to allow narrow,
      precise forward redistribution of flux, utilizing the solar resource at the
      maximum quantum efficiency possible in living cells. The synthetic iridocytes are
      composed of silica nanoparticles in microspheres embedded in gelatin, both are
      low refractive index materials and inexpensive. They show wavelength selectivity,
      have little loss (the back-scattering intensity is reduced to less than ~0.01% of
      the forward-scattered intensity), and narrow forward scattering cone similar to
      giant clams. Moreover, by comparing experiments and theoretical calculation, it
      is confirmed that the nonuniformity of the scatter sizes is a "feature not a bug"
      of the design, allowing for efficient, forward redistribution of solar flux in a
      micrometer-scaled paradigm. This method is environmentally benign, inexpensive,
      and scalable to produce optical components that will find uses in efficiency
      limited solar conversion technologies, heat sinks, and biofuel production.

PMID- 29034979
TI  - The role of intragroup agonism in parent-offspring relationships and natal
      dispersal in monogamous owl monkeys (Aotus azarae) of Argentina.
AB  - Agonistic behaviors are common in many group-living taxa and may serve a variety
      of functions, ranging from regulating conflicts over reproduction to defending
      food resources. However, high rates of agonism are not expected to occur among
      close relatives or individuals in established mating relationships, which are
      characteristics of monogamous groups. To contribute to our understanding of
      agonism within socially monogamous groups, we collected behavioral and
      demographic data from Azara's owl monkeys (Aotus azarae) in the Gran Chaco of
      Argentina over 14 years. We examined factors related to age, sex, kinship, and
      behavioral context to evaluate predictions of the hypotheses that agonism
      functions to regulate dispersal and that it mediates competition for food and/or
      mates. Intragroup agonism was relatively rare: the group rate was approximately
      one event every three and a half hours. Rates of agonism were generally similar
      for both sexes, but there were marked differences among age categories. Agonism
      performed by adults was more frequently directed at subadults than at younger
      offspring. In contrast, agonistic interactions involving infants were very rare.
      Among interactions between adults and subadults, adults were much more frequently
      the actors than the recipients, suggesting that agonism from adults may influence
      natal dispersal of subadults. Agonistic events were most frequent during
      foraging, but also occurred more frequently than expected during bouts of social
      behavior. Overall, our results suggest that agonism in owl monkeys serves as a
      mechanism for regulating dispersal, and also likely plays a role in mediating
      mating and feeding competition.

PMID- 29034981
TI  - Review article: the gut microbiome in inflammatory bowel disease-avenues for
      microbial management.
AB  - BACKGROUND: The concept of an altered collective gut microbiota rather than
      identification of a single culprit is possibly the most significant development
      in inflammatory bowel disease research. We have entered the "omics" era, which
      now allows us to undertake large-scale/high-throughput microbiota analysis which
      may well define how we approach diagnosis and treatment of inflammatory bowel
      disease (IBD) in the future, with a strong steer towards personalised
      therapeutics. AIM: To assess current epidemiological, experimental and clinical
      evidence of the current status of knowledge relating to the gut microbiome, and
      its role in IBD, with emphasis on reviewing the evidence relating to microbial
      therapeutics and future microbiome modulating therapeutics. METHODS: A Medline
      search including items 'intestinal microbiota/microbiome', 'inflammatory bowel
      disease', 'ulcerative colitis', 'Crohn's disease', 'faecal microbial
      transplantation', 'dietary manipulation' was performed. RESULTS: Disease
      remission and relapse are associated with microbial changes in both mucosal and
      luminal samples. In particular, a loss of species richness in Crohn's disease has
      been widely observed. Existing therapeutic approaches broadly fall into 3
      categories, namely: accession, reduction or indirect modulation of the
      microbiome. In terms of microbial therapeutics, faecal microbial transplantation
      appears to hold the most promise; however, differences in study
      design/methodology mean it is currently challenging to elegantly translate
      results into clinical practice. CONCLUSIONS: Existing approaches to modulate the
      gut microbiome are relatively unrefined. Looking forward, the future of
      microbiome-modulating therapeutics looks bright with several novel
      strategies/technologies on the horizon. Taken collectively, it is clear that
      ignoring the microbiome in IBD is not an option.

PMID- 29034982
TI  - Bonding Scheme and Optical Properties in BiM2 O2 (PO4 ) (M=Cd, Mg, Zn);
      Experimental and Theoretical Analysis.
AB  - Luminescence properties of the Bi(M,M')2 PO6 (M=Mg, Zn, Cd) series have been
      rationalized as a function of the M element using optical spectroscopy, as well
      as empirical and first principles calculations. The latter yielded indirect band
      gaps for all compounds with energies between 2.64 and 3.62 eV, whereas
      luminescence measurements exhibit bright warm white emission luminescence even at
      room temperature assigned to Bi3+ transitions with, for example, 22.8 % quantum
      yield for M=Mg. The energies of the excitation maxima are shifted with the
      covalent character of the Bi-O bond by inductive effects of the neighboring M-O
      bonds. This is discussed on the basis of empirical and electronic structure
      calculations. Strikingly, in all the investigated compounds, an excitation
      process occurring at energies higher than the band gaps is observed, which seems
      to be intrinsic to the s2 ->sp electronic transitions of the Bi3+ ions.
      Concerning the emission process, a direct correlation between the lone pair (LP)
      activity and the emission energy upon change of the lattice parameters was
      established governing the LP stereo-activity in the BiMg2-x Cdx PO6 system. As a
      result, the possibility for tunable optical properties appears realistic in the
      Bi2 O3 -MO-X2 O5 (X=P, V, As, etc.) systems taking into account the diversity of
      reported or novel crystal structures that can be designed using well-established
      rules of crystal chemistry.

PMID- 29034983
TI  - Pleth variability index can predict spinal anaesthesia-induced hypotension in
      patients undergoing caesarean delivery.
AB  - BACKGROUND: Spinal anaesthesia carries a risk of hypotension. We hypothesized
      that pleth variability index and perfusion index would assess maternal volume
      status, and thus, allow identification of patients at higher risk of developing
      hypotension after spinal anaesthesia for caesarean delivery. METHODS: Fifty
      patients undergoing elective caesarean delivery were enrolled. All patients
      received spinal anaesthesia with 0.5% hyperbaric bupivacaine (10 mg) and fentanyl
      (10 mcg). Blood pressure was measured every minute. Pleth variability index and
      perfusion index were automatically measured throughout the procedure using pulse
      oximetry on the index finger. In case of hypotension (systolic blood pressure
      below 90 mmHg or 80% of the baseline value), ephedrine 5 mg was administered.
      Receiver-operating characteristic and multivariate logistic regression analyses
      for spinal anaesthesia-induced hypotension were performed. RESULTS: Hypotension
      occurred in 32 patients (64%). The areas under the receiver-operating
      characteristic curve were 0.751 (95% confidence interval: 0.597-0.904) for pleth
      variability index before anaesthesia, 0.793 (95% confidence interval: 0.655
      0.930) for pleth variability index after anaesthesia and 0.731 (95% confidence
      interval: 0.570-0.892) for perfusion index change (percent change in perfusion
      index induced by spinal anaesthesia). The optimal threshold value of pleth
      variability index (after anaesthesia) for predicting hypotension was 18%
      (sensitivity: 78.1%, specificity: 83.3%). Pleth variability index after spinal
      anaesthesia was an independent factor for hypotension (odds ratio: 1.21, P =
      0.041). CONCLUSIONS: Pleth variability index after spinal anaesthesia was a good
      predictor of spinal anaesthesia-induced hypotension in patients undergoing
      caesarean delivery. In addition, perfusion index change after spinal anaesthesia
      has the potential to predict hypotension.

PMID- 29034984
TI  - Sensory quality and fatty acid content of springbok (Antidorcas marsupialis)
      meat: influence of farm location and sex.
AB  - BACKGROUND: Springbok are harvested for meat production irrespective of farm
      location or sex from which the meat is derived. The present study investigated
      the influence of farm location (three farms containing different vegetation
      types) and sex on the sensory quality of springbok longissimus thoracis et
      lumborum muscle. The sensory profile (aroma, flavour and texture) was determined
      by descriptive sensory analysis, in addition to determination of the physical
      meat quality, proximate and fatty acid composition. RESULTS: Farm location had a
      significant influence on the sensory quality (gamey and liver-like aroma; beef,
      liver-like, lamb-like and herbaceous flavour; sweet taste; tenderness; residue;
      mealiness; Warner-Bratzler shear force; moisture, protein and intramuscular lipid
      content) and fatty acid content (oleic acid; alpha-linolenic acid; total
      saturated and monounsaturated fatty acids; polyunsaturated to saturated fatty
      acid ratio; total omega-3 polyunsaturated fatty acid; and omega-6 to omega-3
      polyunsaturated fatty acid ratio) of springbok meat. Sex influenced the chemical
      composition of springbok meat; however, the influence on the sensory profile was
      minor (sweet taste; P < 0.001). CONCLUSION: Farm location could influence the
      sensory quality and composition of springbok meat and should be considered when
      harvesting for meat production. Sex does not have to be considered for the
      marketing of springbok meat. (c) 2017 Society of Chemical Industry.

PMID- 29034985
TI  - Burden of atrial fibrillation in Maori and Pacific people in New Zealand: a
      cohort study.
AB  - BACKGROUND: Atrial fibrillation (AF) is a major risk factor for ischaemic stroke
      and cardiovascular events. In New Zealand (NZ), Maori (indigenous New Zealanders)
      and Pacific people experience higher rates of AF compared with non-Maori/non
      Pacific people. AIM: To describe a primary care population with AF in NZ. Stroke
      risk and medication adherence according to ethnicity are also detailed. METHODS:
      Electronic medical records for adults (>=20 years, n = 135 840, including 19 918
      Maori and 43 634 Pacific people) enrolled at 37 NZ general practices were
      analysed for AF diagnosis and associated medication prescription information.
      RESULTS: The overall prevalence of non-valvular AF (NVAF) in this population was
      1.3% (1769), and increased with age (4.4% in people >=55 years). Maori aged >=55
      years were more likely to be diagnosed with NVAF (7.3%) than Pacific (4.0%) and
      non-Maori/non-Pacific people (4.1%, P < 0.001). Maori and Pacific NVAF patients
      were diagnosed with AF 10 years earlier than non-Maori/non-Pacific patients
      (median age of diagnosis: Maori = 60 years, Pacific = 61 years, non-Maori/non
      Pacific = 71 years, P < 0.001). Overall, 67% of NVAF patients were at high risk
      for stroke (CHA2 DS2 -VASc >= 2) at the time of AF diagnosis. Almost half (48%)
      of Maori and Pacific NVAF patients aged <65 years were at high risk for stroke,
      compared with 22% of non-Maori/non-Pacific (P < 0.001). Irrespective of ethnic
      group, adherence to AF medication was suboptimal in those NVAF patients with a
      high risk of stroke or with stroke history. CONCLUSION: AF screening and stroke
      thromboprophylaxis in Maori and Pacific people could start below the age of 65
      years in NZ.

PMID- 29034986
TI  - Access to a youth-specific service for young adults with type 1 diabetes mellitus
      is associated with decreased hospital length of stay for diabetic ketoacidosis.
AB  - BACKGROUND: Management of type 1 diabetes mellitus in youth with diabetes (YWD)
      is complex, and glycaemic control often deteriorates during this challenging
      period. We hypothesise that attendance at a youth-specific diabetes clinic
      reduces hospital admission rates and length of stay (LOS) for diabetic
      ketoacidosis (DKA). AIMS: To assess the impact of a youth-specific diabetes
      service for YWD on DKA admissions in two adjacent local health districts.
      METHODS: A retrospective cohort analysis of admissions for DKA in YWD aged 15-25
      years, presenting to four hospitals in Western Sydney in 2011 was performed.
      Number of admissions, LOS and DKA severity were assessed. Cost was analysed as a
      function of LOS. Groups were divided by attendance at a youth-specific diabetes
      service and no record of attendance. RESULTS: There were 55 DKA admissions from
      39 patients (median age 20.0 years); the majority of admissions (82%) was YWD not
      supported by a youth-specific diabetes service. Median LOS was significantly
      longer in the unsupported group (3.0 vs 1.5 days, P = 0.028). Median pH at
      presentation in the unsupported group was significantly lower, 7.11 versus 7.23
      (P = 0.05). The admission rate was four times greater for those not supported by
      youth-specific diabetes services, 5.5% compared with 1.6% (P = 0.001). The
      estimated cost saved by youth-specific services was over $250,000 pa.
      CONCLUSIONS: Lack of access to supported care for YWD during transition from
      paediatric to adult care has an adverse impact on subsequent DKA admission rates
      and LOS.

PMID- 29034987
TI  - Global-scale impacts of nitrogen deposition on tree carbon sequestration in
      tropical, temperate, and boreal forests: A meta-analysis.
AB  - Elevated nitrogen (N) deposition may increase net primary productivity in N
      limited terrestrial ecosystems and thus enhance the terrestrial carbon (C) sink.
      To assess the magnitude of this N-induced C sink, we performed a meta-analysis on
      data from forest fertilization experiments to estimate N-induced C sequestration
      in aboveground tree woody biomass, a stable C pool with long turnover times. Our
      results show that boreal and temperate forests responded strongly to N addition
      and sequestered on average an additional 14 and 13 kg C per kg N in aboveground
      woody biomass, respectively. Tropical forests, however, did not respond
      significantly to N addition. The common hypothesis that tropical forests do not
      respond to N because they are phosphorus-limited could not be confirmed, as we
      found no significant response to phosphorus addition in tropical forests. Across
      climate zones, we found that young forests responded more strongly to N addition,
      which is important as many previous meta-analyses of N addition experiments rely
      heavily on data from experiments on seedlings and young trees. Furthermore, the C
      N response (defined as additional mass unit of C sequestered per additional mass
      unit of N addition) was affected by forest productivity, experimental N addition
      rate, and rate of ambient N deposition. The estimated C-N responses from our meta
      analysis were generally lower that those derived with stoichiometric scaling,
      dynamic global vegetation models, and forest growth inventories along N
      deposition gradients. We estimated N-induced global C sequestration in tree
      aboveground woody biomass by multiplying the C-N responses obtained from the meta
      analysis with N deposition estimates per biome. We thus derived an N-induced
      global C sink of about 177 (112-243) Tg C/year in aboveground and belowground
      woody biomass, which would account for about 12% of the forest biomass C sink
      (1,400 Tg C/year).

PMID- 29034988
TI  - The global Filipino nurse: An integrative review of Filipino nurses' work
      experiences.
AB  - AIM: To understand the work-related experiences of Philippine-trained nurses
      working globally. BACKGROUND: The Philippines is a major source country of
      foreign-trained nurses located globally. However, there is paucity of research on
      professional factors and career related issues affecting foreign-trained nurses'
      work experiences. METHODS: An integrative review through a comprehensive search
      of literature was undertaken from November 2015 and was repeated in August 2016.
      Seven articles satisfied the selection criteria. RESULTS: Filipino nurses
      experienced differences in the practice of nursing in terms of work process,
      roles and autonomy. Moreover, they encountered challenges such as work-related
      discrimination and technical difficulties within the organisation. CONCLUSION: A
      clear understanding of Filipino nurses' work experiences and the challenges they
      have encountered suggests identification of important constructs influencing
      effective translation of nursing practice across cultures and health systems,
      which then form the basis for support strategies. IMPLICATION FOR NURSING
      MANAGEMENT: It is critical to recognize foreign-trained nurses' experience of
      work-related differences and challenges as these foster favorable conditions for
      the management team to plan and continually evaluate policies around recruitment,
      retention and support offered to these nurses. Furthermore, findings suggest
      internationalization of nursing framework and standards integrating a
      transcultural paradigm among staff members within a work organisation.

PMID- 29034989
TI  - Neurological presentations revealing acquired copper deficiency: diagnosis
      features, aetiologies and evolution in seven patients.
AB  - BACKGROUND: Acquired copper deficiency (ACD) is a rare condition usually
      diagnosed from haematological changes. AIMS: To characterise the diagnosis
      features and the evolution of patients with ACD revealed by neurological
      symptoms. METHODS: Clinical, biological and magnetic resonance imaging (MRI) data
      were prospectively analysed at diagnosis and during follow up under copper
      supplementation. RESULTS: Seven patients were studied over a 5-year period. Time
      to diagnosis ranged from 2.5 to 15 months. Subacute ascending paraesthesias and
      gait disorder were the first symptoms. All patients had a posterior cord syndrome
      (PCS) with sensory ataxic gait associated with superficial hypoesthesia of the
      feet; 50% had also lateral cord signs. Electrodiagnostic tests diagnosed a lower
      limb sensory neuropathy in four patients. Spinal cord MRI was normal in three of
      seven patients. Anaemia and lymphopenia were diagnosed in six of seven patients.
      Serum copper was always low, and urinary copper was low or normal. Serum and
      urinary zinc were high in four patients. Decreased copper intake
      (stoma/parenteral nutrition, malnutrition, malabsorption with lack of vitamin
      supplementation after bariatric or other digestive surgeries) was found in four
      patients, and the chronic use of denture adhesive paste containing zinc was
      discovered in four patients. One patient had both the causes recorded. After
      copper supplementation, copper balance and then haematological disturbances were
      the first features to normalise gradually in 2 months. Radiological myelitis
      disappeared in 10 months, whereas neurological symptoms improved in six of seven
      patients after a mean follow up of 2 years. CONCLUSIONS: Progressive PCS with
      anaemia and lymphopenia must raise the possibility of an ACD. Early copper
      supplementation could increase the neurological prognosis.

PMID- 29034990
TI  - How disturbance, competition, and dispersal interact to prevent tree range
      boundaries from keeping pace with climate change.
AB  - Climate change is expected to cause geographic shifts in tree species' ranges,
      but such shifts may not keep pace with climate changes because seed dispersal
      distances are often limited and competition-induced changes in community
      composition can be relatively slow. Disturbances may speed changes in community
      composition, but the interactions among climate change, disturbance and
      competitive interactions to produce range shifts are poorly understood. We used a
      physiologically based mechanistic landscape model to study these interactions in
      the northeastern United States. We designed a series of disturbance scenarios to
      represent varied disturbance regimes in terms of both disturbance extent and
      intensity. We simulated forest succession by incorporating climate change under a
      high-emissions future, disturbances, seed dispersal, and competition using the
      landscape model parameterized with forest inventory data. Tree species range
      boundary shifts in the next century were quantified as the change in the location
      of the 5th (the trailing edge) and 95th (the leading edge) percentiles of the
      spatial distribution of simulated species. Simulated tree species range boundary
      shifts in New England over the next century were far below (usually <20 km) that
      required to track the velocity of temperature change (usually more than 110 km
      over 100 years) under a high-emissions scenario. Simulated species' ranges
      shifted northward at both the leading edge (northern boundary) and trailing edge
      (southern boundary). Disturbances may expedite species' recruitment into new
      sites, but they had little effect on the velocity of simulated range boundary
      shifts. Range shifts at the trailing edge tended to be associated with
      photosynthetic capacity, competitive ability for light and seed dispersal
      ability, whereas shifts at the leading edge were associated only with
      photosynthetic capacity and competition for light. This study underscores the
      importance of understanding the role of interspecific competition and disturbance
      when studying tree range shifts.

PMID- 29034991
TI  - Concept analysis: Role ambiguity in senior nursing students.
AB  - Role ambiguity is a lack of clarity or uncertainty related to one's position or
      role. Role ambiguity has been documented in the literature in relationship to
      athletics, industry, business, education, and nursing. However, a concept
      analysis has not been performed. Therefore, the process of concept analysis
      outlined by Walker and Avant is now used to look at the concept of role ambiguity
      and its relevance to senior nursing students' socialization and education into
      the profession of nursing. Attributes, antecedents, consequences, and empiric
      referents are discussed and theories commonly associated with role ambiguity are
      presented. At the end of the analysis, an operational definition is provided for
      use in exploring the concept of role ambiguity as it relates to senior nursing
      students' articulation of the role of the professional nurse.

PMID- 29034992
TI  - Combined prognostic value of pretreatment anemia and cervical node necrosis in
      patients with nasopharyngeal carcinoma receiving intensity-modulated
      radiotherapy: A large-scale retrospective study.
AB  - This study investigated the combined prognostic value of pretreatment anemia and
      cervical node necrosis (CNN) in patients with nasopharyngeal carcinoma (NPC).
      Retrospective review of 1302 patients with newly diagnosed nonmetastatic NPC
      treated with intensity-modulated radiotherapy (IMRT) +/- chemotherapy. Patients
      were classified into four groups according to anemia and CNN status. Survival was
      compared using the log-rank test. Independent prognostic factors were identified
      using the Cox proportional hazards model. The primary end-point was overall
      survival (OS); secondary end-points were disease-free survival (DFS),
      locoregional relapse-free survival (LRRFS), and distant metastasis-free survival
      (DMFS). Pretreatment anemia was an independent, adverse prognostic factor for
      DMFS; pretreatment CNN was an independent adverse prognostic factor for all end
      points. Five-year survival for non-anemia and non-CNN, anemia, CNN, and anemia
      and CNN groups were: OS (93.1%, 87.2%, 82.9%, 76.3%, P < 0.001), DFS (87.0%,
      84.0%, 73.9%, 64.6%, P < 0.001), DMFS (94.1%, 92.1%, 82.4%, 72.5%, P < 0.001),
      and LRRFS (92.8%, 92.4%, 88.7%, 84.0%, P = 0.012). The non-anemia and non-CNN
      group had best survival outcomes; anemia and CNN group, the poorest. Multivariate
      analysis demonstrated combined anemia and CNN was an independent prognostic
      factor for OS, DFS, DMFS, and LRRFS (P < 0.05). The combination of anemia and CNN
      is an independent adverse prognostic factor in patients with NPC treated using
      IMRT +/- chemotherapy. Assessment of pretreatment anemia and CNN improved risk
      stratification, especially for patients with anemia and CNN who have poorest
      prognosis. This study may aid the design of individualized treatment plans to
      improve treatment outcomes.

PMID- 29034993
TI  - Impact of marital status at diagnosis on survival and its change over time
      between 1973 and 2012 in patients with nasopharyngeal carcinoma: a propensity
      score-matched analysis.
AB  - The impact of marital status at diagnosis on survival outcomes and its change
      over time in patients with nasopharyngeal carcinoma (NPC) are unclear. The
      Surveillance, Epidemiology, and End Results (SEER) database was used to identify
      patients diagnosed with NPC in the United States from 1973 to 2012. A primary
      comparison (married vs. unmarried) was implemented with 1:1 propensity score
      matching. Secondary comparisons were performed individually between three
      unmarried subgroups (single, separated/divorced, widowed) and married group. The
      effect of marital status on cause-specific survival (CSS) and overall survival
      (OS) were evaluated using univariate/multivariate analysis. Moreover, we
      investigated the change over time (1973-2012) in the effect of marital status on
      NPC survival. Married patients had better 5-year CSS/OS than unmarried patients
      (61.1% vs. 52.6%, P < 0.001; 55.6% vs. 45.3%, P < 0.001, respectively). In
      multivariate analysis, unmarried patients had significantly poorer CSS/OS than
      married patients (adjusted hazard ratio [aHR] = 1.35, P < 0.001; aHR = 1.40, P <
      0.001, respectively). The survival benefit of being married was only detected in
      non-Hispanic white and Chinese American patients. Single, separated/divorced, and
      widowed patients had significantly poorer CSS/OS than married patients (aHR =
      1.37 and 1.37; 1.46 and 1.42; 1.43 and 1.48, respectively; all P < 0.001). The
      change over time in the effect of marital status on survival was more stable in
      male than female. The strength of the negative effect of separated/divorced and
      widowed status showed a downward and upward trend, respectively. Gender
      difference in the adverse effect of single status on NPC survival became smaller
      over time. Only non-Hispanic white and Chinese American patients with NPC obtain
      survival benefits from married status. Single and widowed patients are regarded
      as high-risk population.

PMID- 29034994
TI  - Risk factors of lymph node metastasis in patients with non-small cell lung cancer
      <= 2 cm in size: A monocentric population-based analysis.
AB  - AIM: This study was designed to determine the risk factors of lymph node
      metastasis in non-small cell lung cancer (NSCLC) patients with tumors <= 2 cm,
      using the Shanghai Chest Hospital Lung Cancer Database. METHODS: Five hundred and
      eighteen patients with NSCLC <= 2 cm were included in this study, and were
      classified into lymph node-positive and lymph node-negative groups. Univariate
      and multivariate logistic regression analyses were performed to select the
      independent risk factors for lymph node metastasis in NSCLC patients. RESULTS: No
      evidence of metastasis was found in tumors <= 1 cm, all positive results were in
      tumors sized 1-2 cm. Imaging characteristics, including solid and part-solid
      nodules, were strongly associated with lymph node metastasis (odds ratio [OR]
      24.959, 95% confidence interval [CI] 5.999-103.835, P < 0.001; OR 12.559, 95% CI
      3.564-44.259, P < 0.001) and subgroup logistic analysis (OR 21.384, 95% CI 5.058
      90.407, P < 0.001; OR 11.632, 95% CI 3.290-41.126, P < 0.001). Greater lymph node
      metastasis was observed in non-adeno non-squamous carcinoma. The presence of
      pleural invasion and carcinoembryonic antigen levels indicated lymph node
      dissection. Similar results were revealed in subgroup analysis in tumors <= 2 to
      > 1 cm. CONCLUSION: Size had a great impact on lymph node metastasis, especially
      tumors of 1-2 cm. Preoperative imaging, non-adeno non-squamous carcinoma, pleural
      invasion, and carcinoembryonic antigen all indicated lymph node dissection. There
      was no discrepancy between N1 and N2 positive lymph nodes.

PMID- 29034996
TI  - Interleukin 1beta polymorphism and serum level are associated with pediatric
      asthma.
AB  - BACKGROUND AND AIM: Interleukin-1 is a pro-inflammatory cytokine found in two
      forms (alpha and beta). The alpha form is mainly cell-bound, whereas IL-1beta is
      primarily secreted by macrophages in response to immune system stimulation. We
      hypothesized that polymorphic variants of interleukin 1 genes may play a role in
      childhood asthma risk. The aim of this study was to investigate if IL-1alpha and
      beta polymorphism is associated with asthma in a pediatric population and if the
      genotype affects its serum level. METHODS: The studied population included 310
      children aged 6-18 years old (152 with asthma and 158 healthy children).
      Genotypes were determined with real-time PCR method using TaqMan Genotyping
      Assays. Serum level was measured with ELISA Set. Statistical analysis was done in
      Statistica v.12.0. Linkage disequilibrium and haplotype analysis was done in
      Haploview v. 4.2. RESULTS: We found that three IL-1beta polymorphisms rs1143634,
      rs1143633, and rs1143643 were associated with allergic asthma risk (P = 0.034; OR
      = 1.523; P = 0.024, OR = 1.477; 0.044, OR = 1.420, respectively). We also found a
      strong linkage disequilibrium between these polymorphisms and CAC haplotype was
      associated significantly with asthma risk (P = 0.023). For IL1alpha, we did not
      observe association with asthma. We then analyzed if IL-1beta expression was
      altered in serum and we found that asthmatic children showed significantly higher
      IL-1beta levels than healthy controls (P = 0.047). No association with asthma was
      observed for IL-1 alpha variants. CONCLUSIONS: This study indicates that IL-1beta
      gene polymorphism may affect allergic asthma risk in children.

PMID- 29034997
TI  - Everything You Always Wanted to Know about Poly-l-lysine Dendrigrafts (But Were
      Afraid to Ask).
AB  - Less than a decade ago, dendrigrafts of poly-l-lysine (DGLs) joined the family of
      polycationic dendritic macromolecules. Resulting from the iterative
      polycondensation of an N-carboxyanhydride in water, four generations of the
      dendrigraft can be obtained on a multigram scale and without chromatographic
      purification. DGLs share features with both dendrimers and hyperbranched
      polymers, but turned out to have unique biophysical and bioactive properties. The
      macromolecules-in their native form or functionalized-have been extensively
      characterized by various analytical and computational methods, and have already
      found numerous applications in the biomedical field, such as drug and gene
      delivery, biomaterials, tissue engineering, bioimaging, and biosensing. Despite a
      growing interest for DGLs, there is still plenty of room for further exciting
      developments that could result from a better exposure of these macromolecules,
      which is the ambition of this short review.

PMID- 29034995
TI  - miR-1 suppresses the proliferation and promotes the apoptosis of esophageal
      carcinoma cells by targeting Src.
AB  - Nonreceptor tyrosine kinase c-Src, also known as Src, is a potent oncogene
      involved in a series of biological processes including cell growth,
      differentiation, and apoptosis; however, its expression pattern and function in
      esophageal cancer is poorly addressed. In this study, abnormal overexpression of
      Src protein was observed in esophageal cancer tissues, which fuelled the
      speculation that microRNA-mediated posttranscriptional regulatory mechanism might
      be involved. Bioinformatic analyses were applied to identify miRNAs that could
      potentially target Src. miR-1 was predicted and further validated as a direct
      repressor of Src. Moreover, we manipulated knockdown and overexpression
      experiment on TE-1 and TE-10 cells to demonstrate miR-1 suppressed proliferation
      and promoted apoptosis in esophageal cancer cells by inhibiting Src. Taken
      together, this study underlines a negative regulatory mechanism in which miR-1
      serves as a suppressor of Src in esophageal cancer cells and may provide insights
      into novel therapeutic approaches for esophageal cancer.

PMID- 29034999
TI  - Home supply of emergency oral steroids and reduction in asthma healthcare
      utilization.
AB  - OBJECTIVE: To determine if children with moderate-to-severe persistent asthma
      have decreased healthcare utilization after receiving a prescription and
      instructions to use an at home emergency supply of oral steroids during asthma
      exacerbations. METHODS: A quasi-experimental design study with a historical
      control from retrospective chart review was performed for patients aged 2-18
      years seen in a tertiary care pediatric pulmonary clinic for moderate to severe
      persistent asthma. Baseline utilization of the emergency department, inpatient
      hospital, and pediatric intensive care unit for asthma exacerbations was
      collected from 24 months prior to initial prescription for at home steroids and
      compared with 12 months post-intervention using Poisson Regression. A subgroup
      analysis was performed for ages 6-18 evaluating school age children alone.
      RESULTS: Patients (N = 132) were averaged 10 years +/- 3.9 years of age and 57%
      of patients were male. Emergency Department visit rates significantly declined in
      the 12 months after receiving a prescription and instructions for home emergency
      steroid supply compared with the 12 months prior to this intervention (0.39
      visits/patient/year vs 0.67, P < 0.01). There was a trend for a decline in
      inpatient (0.27 visits/patient/year vs 0.11, P = 0.09) and pediatric intensive
      care unit stay rates (0.11 visits/patient/year vs 0.05, P = 0.06). A subgroup
      analysis of ages 6-18 found similar results. CONCLUSIONS: Incorporation of home
      emergency oral steroids into the home management plan of children with moderate
      to-severe asthma can reduce asthma related Emergency Department visits.

PMID- 29034998
TI  - The albumin-bilirubin grade uncovers the prognostic relationship between hepatic
      reserve and immune dysfunction in HIV-associated hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of liver-related
      mortality in people living with HIV, where co-infection with hepatotropic viruses
      accelerates the course of chronic liver disease. AIM: To evaluate whether the
      albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in
      HCC, might identify patients with progressive liver dysfunction in the context of
      HIV/hepatitis co-infection. METHODS: Using uni- and multi-variable analyses, we
      studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a
      large, multi-center cohort of patients with HIV-associated HCC recruited from 44
      centres in 9 countries within the Liver Cancer in HIV study group. Patients who
      underwent liver transplantation were excluded. RESULTS: A total of 387 patients,
      predominantly HCV co-infected (78%) with balanced representation of all Barcelona
      Clinic Liver Cancer (BCLC) stages (A = 33%, B = 18%, C = 37%, D = 12%) were
      recruited. At HCC diagnosis, 84% had been on anti-retrovirals for a median
      duration of 8.8 years. The albumin-bilirubin grade identified significant
      differences in median survival of 97 months for grade 1 (95% CI 13-180 months),
      17 months for grade 2 (95% CI 11-22 months) and 6 months for grade 3 (95% CI 4-9
      months, P < .001). A more advanced albumin-bilirubin grade correlated with lower
      CD4 counts (464/373/288 cells/mm3 for grades 1/2/3) and higher HIV viraemia
      (3.337/8.701/61.845 copies/mL for grades 1/2/3, P < .001). CONCLUSIONS: In this
      large, multi-center retrospective study, the albumin-bilirubin grade highlights
      the interplay between liver reserve and immune dysfunction as prognostic
      determinants in HIV-associated HCC.

PMID- 29035001
TI  - News & Announcements: American Society for Laser Medicine and Surgery, Inc.

PMID- 29035000
TI  - Use of sacubitril/valsartan in acute decompensated heart failure: a case report.
AB  - Refractory heart failure typically requires costly long-term, continuous
      intravenous inodilator infusions while patients await mechanical circulatory
      support or cardiac transplantation. The combined angiotensin receptor blocker
      neprilysin inhibitor, sacubitril/valsartan, is a novel therapy that can increase
      levels of endogenous vasoactive peptides. This therapy has been recommended as an
      alternative agent in patients with chronic heart failure with reduced ejection
      fraction and New York Heart Association class II-III symptoms. Here, we report a
      case of a patient with refractory stage D heart failure with reduced ejection
      fraction who was successfully weaned off continuous intravenous inodilator
      support using sacubitril/valsartan after prior failed attempts using standard
      therapies.

PMID- 29035002
TI  - Short-term risk of hepatocellular carcinoma after hepatitis C virus eradication
      following direct-acting anti-viral treatment.
AB  - BACKGROUND: With the development of direct-acting anti-virals (DAAs), almost all
      patients with chronic hepatitis C virus (HCV) infection can achieve sustained
      viral response (SVR). AIM: To evaluate the short-term risk of HCC among patients
      with SVR by DAAs, including those with cirrhosis or previous HCC. METHODS: This
      large-scale, multicentre cohort study included 1,675 consecutive patients who
      achieved SVR by treatment with interferon-free sofosbuvir-based regimens, divided
      into groups with (n = 152) or without previous HCC (n = 1,523). The Kaplan-Meier
      method and Cox proportional hazard analysis were used to calculate the cumulative
      HCC incidence and related factors of HCC. RESULTS: During the follow-up period
      (median: 17 months), 46 (2.7%) patients developed HCC. The 1-year cumulative
      rates of de novo HCC were 0.4% and 4.9% for the noncirrhosis and cirrhosis groups
      respectively (log-rank test: P < 0.001). For cirrhotic patients, serum alpha
      fetoprotein level at the end of treatment (EOT-AFP) was the strongest predictor
      of de novo HCC. The 1-year cumulative de novo HCC rates were 1.4% and 13.1% in
      the EOT-AFP < 9.0 ng/mL and >= 9.0 ng/mL groups (cut-off value) respectively (log
      rank test: P < 0.001). The 1-year cumulative rates of HCC recurrence were 6.5%
      and 23.1% for the noncirrhosis and cirrhosis groups respectively (log-rank test:
      P = 0.023). For cirrhotic patients, previous HCC characteristics were
      significantly associated with HCC recurrence. In contrast, sex, age and metabolic
      features did not influence de novo HCC or recurrence. CONCLUSIONS: For cirrhotic
      patients after elimination of HCV, serum EOT-AFP level and previous HCC
      characteristics would be useful markers for predicting de novo HCC or recurrence.

PMID- 29035003
TI  - Review article: hepatitis B core-related antigen (HBcrAg): an emerging marker for
      chronic hepatitis B virus infection.
AB  - BACKGROUND: Chronic hepatitis B (CHB) cannot be completely eradicated due to the
      presence of covalently closed circular DNA (cccDNA) in the nuclei of infected
      hepatocytes. While quantification of intrahepatic cccDNA requires liver biopsies,
      serological markers can be non-invasive alternatives to reflect intrahepatic
      viral replicative activity. Recently, hepatitis B core-related antigen (HBcrAg)
      has been advocated as a novel serum marker for disease monitoring and
      prognostication of CHB. AIM: To examine the virological aspect and clinical
      application of HBcrAg with respect to the natural history and treatment of CHB.
      METHODS: We reviewed all papers published in the PubMed journal list and
      abstracts from major international meetings that included the keyword "HBcrAg" or
      "hepatitis B core-related antigen" until March 2017. Selected studies were
      compared and summarised on the basis of existing theories, as well as the
      authors' experience. RESULTS: HBcrAg exhibited good correlation with intrahepatic
      (ih) cccDNA, ih total hepatitis B virus (HBV) DNA, serum HBV DNA and to a lesser
      extent HBV surface antigen (HBsAg). In situations where serum HBV DNA levels
      become undetectable or HBsAg loss is achieved, HBcrAg can still be detectable.
      This marker is helpful in differentiation of HBeAg-negative chronic hepatitis
      from HBeAg-negative chronic infection, predicting spontaneous or treatment
      induced HBeAg seroconversion, sustained response to nucleos(t)ide analogue (NA),
      risk of HBV reactivation in occult HBV infection under immunosuppressive
      therapies, and risk of hepatocellular carcinoma (HCC) development as well as post
      operative HCC recurrence. CONCLUSIONS: HBcrAg is a potential surrogate marker of
      cccDNA. It may soon become a useful marker for disease monitoring, predicting
      treatment response and disease outcome of chronic hepatitis B.

PMID- 29035004
TI  - A protein with an unusually short PPR domain, MEF8, affects editing at over 60
      Arabidopsis mitochondrial C targets of RNA editing.
AB  - An RNA-seq approach was used to investigate the role of a PLS-subfamily
      pentatricopeptide repeat protein, Mitochondrial Editing Factor 8 (MEF8), on
      editing in Arabidopsis mitochondria and plastids. MEF8 has an intact DYW domain,
      but possesses an unusually short PLS repeat region of only five repeats. The MEF8
      T-DNA insertion (mef8) line exhibited reduced editing at 38 mitochondrial editing
      sites and increased editing at 24 sites; therefore the absence of MEF8 affects
      11% of the mitochondrial editome. Notably, 60% of the matR transcripts' sites
      showed a decrease of editing extent in the mef8 mutant. An E549A substitution in
      the MEF8 protein replaced the putatively catalytic glutamate of the HXE motif in
      the DYW domain. Complementation with MEF8-E549A failed to restore editing at the
      main target sites but was able to restore editing at the matR transcript; it also
      decreased the editing extent of most of the C targets exhibiting an increase of
      editing extent in the mef8 mutant plant. Thus, MEF8 has two antagonistic effects
      on mitochondrial editing: stimulatory, which requires a catalytic glutamate for
      most of the targets except for the matR transcript, and inhibitory, for which
      glutamate is dispensable.

PMID- 29035005
TI  - Living Supramolecular Polymerization of a Perylene Bisimide Dye into Fluorescent
      J-Aggregates.
AB  - The self-assembly of a new perylene bisimide (PBI) organogelator with 1,7
      dimethoxy substituents in the bay position affords non-fluorescent H-aggregates
      at high cooling rates and fluorescent J-aggregates at low cooling rates. Under
      properly adjusted conditions, the kinetically trapped "off-pathway" H-aggregates
      are transformed into the thermodynamically favored J-aggregates, a process that
      can be accelerated by the addition of J-aggregate seeds. Spectroscopic studies
      revealed a subtle interplay of pi-pi interactions and intra- and intermolecular
      hydrogen bonding for monomeric, H-, and J-aggregated PBIs. Multiple
      polymerization cycles initiated from the seed termini demonstrate the living
      character of this chain-growth supramolecular polymerization process.

PMID- 29035006
TI  - Applying systems thinking to inform studies of wildlife trade in primates.
AB  - Wildlife trade presents a major threat to primate populations, which are in
      demand from local to international scales for a variety of uses from food and
      traditional medicine to the exotic pet trade. We argue that an interdisciplinary
      framework to facilitate integration of socioeconomic, anthropological, and
      biological data across multiple spatial and temporal scales is essential to guide
      the study of wildlife trade dynamics and its impacts on primate populations.
      Here, we present a new way to design research on wildlife trade in primates using
      a systems thinking framework. We discuss how we constructed our framework, which
      follows a social-ecological system framework, to design an ongoing study of
      local, regional, and international slow loris (Nycticebus spp.) trade in Vietnam.
      We outline the process of iterative variable exploration and selection via this
      framework to inform study design. Our framework, guided by systems thinking,
      enables recognition of complexity in study design, from which the results can
      inform more holistic, site-appropriate, and effective trade management practices.
      We place our framework in the context of other approaches to studying wildlife
      trade and discuss options to address foreseeable challenges to implementing this
      new framework.

PMID- 29035007
TI  - Large soil organic carbon increase due to improved agronomic management in the
      North China Plain from 1980s to 2010s.
AB  - Agricultural soils are widely recognized to be capable of carbon sequestration
      that contributes to mitigating CO2 emissions. To better understand soil organic
      carbon (SOC) stock dynamics and its driving and controlling factors corresponding
      with a period of rapid agronomic evolution from the 1980s to the 2010s in the
      North China Plain (NCP), we collected data from two region-wide soil sampling
      campaigns (in the 1980s and 2010s) and conducted an analysis of the controlling
      factors using the random forest model. Between the 1980s and 2010s, environmental
      (i.e. soil salinity/fertility) and societal (i.e. policy/techniques) factors both
      contributed to adoption of new management practices (i.e. chemical fertilizer
      application/mechanization). Results of our work indicate that SOC stocks in the
      NCP croplands increased significantly, which also closely related to soil total
      nitrogen changes. Samples collected near the surface (0-20 cm) and deeper (20-40
      cm) both increased by an average of 9.4 and 5.1 Mg C ha-1 , respectively, which
      are equivalent to increases of 73% and 56% compared with initial SOC stocks in
      the 1980s. The annual carbon sequestration amount in surface soils reached 10.9
      Tg C year-1 , which contributed an estimated 43% of total carbon sequestration in
      all of China's cropland on just 27% of its area. Successful desalinization and
      the subsequent increases in carbon (C) inputs, induced by agricultural projects
      and policies intended to support crop production (i.e. reconstruction of low
      yield farmland, and agricultural subsidies), combined with improved cultivation
      practices (i.e. fertilization and straw return) since the early 1980s were the
      main drivers for the SOC stock increase. This study suggests that rehabilitation
      of NCP soils to reduce salinity and increase crop yields have also served as a
      pathway for substantial soil C sequestration.

PMID- 29035008
TI  - Average mid-sleep time as a proxy for circadian phase.
AB  - Assessments of circadian phase using melatonin are laborious. Sleep-time indices
      allow for less laborious phase calculations, but common indices weakly represent
      melatonin phase. We show how a single sleep-time assessment can represent
      melatonin phase by over 60%, improving the use of subjective sleep to mirror
      objective circadian phase.

PMID- 29035010
TI  - Ecosystem regime shifts disrupt trophic structure.
AB  - Regime shifts between alternative stable ecosystem states are becoming
      commonplace due to the combined effects of local stressors and global climate
      change. Alternative states are characterized as substantially different in form
      and function from pre-disturbance states, disrupting the delivery of ecosystem
      services and functions. On coral reefs, regime shifts are typically characterized
      by a change in the benthic composition from coral to macroalgal dominance. Such
      fundamental shifts in the benthos are anticipated to impact associated fish
      communities that are reliant on the reef for food and shelter, yet there is
      limited understanding of how regime shifts propagate through the fish community
      over time, relative to initial or recovery conditions. This study addresses this
      knowledge gap using long-term data of coral reef regime shifts and recovery on
      Seychelles reefs following the 1998 mass bleaching event. It shows how trophic
      structure of the reef fish community becomes increasingly dissimilar between
      alternative reef ecosystem states (regime-shifted vs. recovering) with time since
      disturbance. Regime-shifted reefs developed a concave trophic structure, with
      increased biomass in base trophic levels as herbivorous species benefitted from
      increased algal resources. Mid trophic level species, including specialists such
      as corallivores, declined with loss of coral habitat, while biomass was retained
      in upper trophic levels by large-bodied, generalist invertivores. Recovering
      reefs also experienced an initial decline in mid trophic level biomass, but moved
      toward a bottom-heavy pyramid shape, with a wide range of feeding groups (e.g.,
      planktivores, corallivores, omnivores) represented at mid trophic levels. Given
      the importance of coral reef fishes in maintaining the ecological function of
      coral reef ecosystems and their associated fisheries, understanding the effects
      of regime shifts on these communities is essential to inform decisions that
      enhance ecological resilience and economic sustainability.

PMID- 29035009
TI  - Prevalence, antibiotic resistance, and MLST typing of Helicobacter pylori in
      Algiers, Algeria.
AB  - BACKGROUND: Helicobacter pylori infection is common in Algeria, but there are few
      data on the characterization of isolated strains. The aim of this study was to
      update data on the prevalence of H. pylori in patients submitted to endoscopy,
      antibiotic resistance, and phylogeography of H. pylori strains isolated in
      Algiers. MATERIALS AND METHODS: This is a prospective study carried out between
      November 2015 and August 2016. The culture of H. pylori was performed on antral
      and fundic gastric biopsies of adult patients from 3 hospitals. A real-time PCR
      using the fluorescence resonance energy transfer (FRET) principle for the
      detection of H. pylori followed by a melting curve analysis for the detection of
      mutations associated with resistance to clarithromycin was applied.
      Differentiation between antral and fundic isolates of the same patient was also
      determined by RAPD, and an MLST typing was performed for characterization of the
      phylogeographic group of H. pylori. RESULTS: By real-time PCR, the prevalence of
      H. pylori infection among the 147 patients included was 57%. Culture was positive
      in only 29% of the cases. Twenty-seven percent of patients had received H. pylori
      eradication treatment. The primary and secondary resistance rates to
      clarithromycin were 23% and 36%, respectively, and to metronidazole, 45% and 71%,
      respectively. Only one isolate was resistant to levofloxacin, and no resistance
      to amoxicillin, tetracycline, and rifampicin was detected. A double population
      was present in 14 patients. The MLST analysis classified the 42 H. pylori strains
      from 38 patients in 2 haplotypes: hpEurope (33) and hpNEAfrica (9). CONCLUSION:
      The prevalence of H. pylori remains high in Algeria but appears to be decreasing
      in recent years. High resistance to clarithromycin requires increased monitoring
      of the evolution of antibiotic resistance and adaptation of eradication therapy.

PMID- 29035011
TI  - Autonomic and Autacoid Pharmacology: Goodbye and thank you.

PMID- 29035012
TI  - Regulatory Effects of Black Rice Extract on Helicobacter pylori Infection-Induced
      Apoptosis.
AB  - SCOPE: Black rice extract (BRE) contains cyanidin 3-O-glucoside (C3G), an
      anthocyanin, as the major component. In this study, we found that BRE inhibits
      the mRNA and protein expression of genes encoding cytotoxin-associated protein A
      (cagA) and vacuolating protein A (vacA) in Helicobacter pylori 60190 strain.
      METHODS AND RESULTS: We performed RT-PCR and western blotting to show that BRE
      inhibits the mRNA and protein expression of SecA. Because SecA is involved in
      VacA export in bacteria, our result suggests a positive correlation between BRE
      induced inhibition of secA expression and VacA secretion. Further, we perform MTT
      assay and flow cytometry to show that BRE decreases the apoptosis of H. pylori
      infected KATO III cells. Finally, we perform western blotting to show that the
      cell-protective effect of BRE is associated with decreased levels of active
      proapoptotic proteins caspases and PARP and increased levels of antiapoptotic
      proteins survivin and XIAP in H. pylori-infected cells. CONCLUSION: Thus, our
      results indicate that BRE acts as a potent inhibitor of the biogenesis of H.
      pylori virulence proteins and decreases the apoptosis of H. pylori-infected
      cells. Moreover, our results suggest that BRE can be used to exert beneficial
      effects in patients with gastroduodenal diseases caused by H. pylori.

PMID- 29035013
TI  - Prebiotics for the prevention of allergies: A systematic review and meta-analysis
      of randomized controlled trials.
AB  - BACKGROUND: Prevalence of allergic diseases in infants is approximately 10%
      reaching 20 to 30% in those with an allergic first-degree relative. Prebiotics
      are selectively fermented food ingredients that allow specific changes in
      composition/activity of the gastrointestinal microflora. They modulate immune
      responses, and their supplementation has been proposed as an intervention to
      prevent allergies. OBJECTIVE: To assess in pregnant women, breastfeeding mothers,
      and infants (populations) the effect of supplementing prebiotics (intervention)
      versus no prebiotics (comparison) on the development of allergic diseases and to
      inform the World Allergy Organization guidelines. METHODS: We performed a
      systematic review of studies assessing the effects of prebiotic supplementation
      with an intention to prevent the development of allergies. RESULTS: Of 446 unique
      records published until November 2016 in Cochrane, MEDLINE, and EMBASE, 22
      studies fulfilled a priori specified criteria. We did not find any studies of
      prebiotics given to pregnant women or breastfeeding mothers. Prebiotic
      supplementation in infants, compared to placebo, had the following effects: risk
      of developing eczema (RR: 0.68, 95% CI: 0.40 to 1.15), wheezing/asthma (RR, 0.37;
      95% CI: 0.17 to 0.80), and food allergy (RR: 0.28, 95% CI: 0.08 to 1.00). There
      was no evidence of an increased risk of any adverse effects (RR: 1.01, 95% CI:
      0.92 to 1.10). Prebiotic supplementation had little influence growth rate (MD:
      0.92 g per day faster with prebiotics, 95% CI: 0 to 1.84) and the final infant
      weight (MD: 0.10 kg higher with prebiotics, 95% CI: -0.09 to 0.29). The certainty
      of these estimates is very low due to risk of bias and imprecision of the
      results. CONCLUSIONS: Currently available evidence on prebiotic supplementation
      to reduce the risk of developing allergies is very uncertain.

PMID- 29035016
TI  - Urolithiasis around the world.

PMID- 29035014
TI  - Nationwide trends in chemotherapy use and survival of elderly patients with
      metastatic pancreatic cancer.
AB  - Despite an aging population and underrepresentation of elderly patients in
      clinical trials, studies on elderly patients with metastatic pancreatic cancer
      are scarce. This study investigated the use of chemotherapy and survival in
      elderly patients with metastatic pancreatic cancer. From the Netherlands Cancer
      Registry, all 9407 patients diagnosed with primary metastatic pancreatic
      adenocarcinoma in 2005-2013 were selected to investigate chemotherapy use and
      overall survival (OS), using Kaplan-Meier and Cox proportional hazard regression
      analyses. Over time, chemotherapy use increased in all age groups (<70 years:
      from 26 to 43%, 70-74 years: 14 to 25%, 75-79 years: 5 to 13%, all P < 0.001, and
      >=80 years: 2 to 3% P = 0.56). Median age of 2,180 patients who received
      chemotherapy was 63 years (range 21-86 years, 1.6% was >=80 years). In
      chemotherapy-treated patients, with rising age (<70, 70-74, 75-79, >=80 years),
      microscopic tumor verification occurred less frequently (91-88-87-77%,
      respectively, P = 0.009) and OS diminished (median 25-26-19-16 weeks, P = 0.003).
      After adjustment for confounding factors, worse survival of treated patients >=75
      years persisted. Despite limited chemotherapy use in elderly age, suggestive of
      strong selection, elderly patients (>=75 years) who received chemotherapy for
      metastatic pancreatic cancer exhibited a worse survival compared to younger
      patients receiving chemotherapy.

PMID- 29035018
TI  - Should we care more about SPARE?

PMID- 29035017
TI  - Stereotactic radiotherapy for primary renal cell carcinoma: time for larger-scale
      prospective studies.

PMID- 29035019
TI  - Getting to the right biopsy in the right patient at the right time.

PMID- 29035020
TI  - Management of urolithiasis in South Asia.

PMID- 29035021
TI  - Microbial communities and organic biomarkers in a Proterozoic-analog sinkhole.
AB  - Little Salt Spring (Sarasota County, FL, USA) is a sinkhole with groundwater
      vents at ~77 m depth. The entire water column experiences sulfidic (~50 MUM)
      conditions seasonally, resulting in a system poised between oxic and sulfidic
      conditions. Red pinnacle mats occupy the sediment-water interface in the sunlit
      upper basin of the sinkhole, and yielded 16S rRNA gene clones affiliated with
      Cyanobacteria, Chlorobi, and sulfate-reducing clades of Deltaproteobacteria. Nine
      bacteriochlorophyll e homologues and isorenieratene indicate contributions from
      Chlorobi, and abundant chlorophyll a and pheophytin a are consistent with the
      presence of Cyanobacteria. The red pinnacle mat contains hopanoids, including 2
      methyl structures that have been interpreted as biomarkers for Cyanobacteria. A
      single sequence of hpnP, the gene required for methylation of hopanoids at the C
      2 position, was recovered in both DNA and cDNA libraries from the red pinnacle
      mat. The hpnP sequence was most closely related to cyanobacterial hpnP sequences,
      implying that Cyanobacteria are a source of 2-methyl hopanoids present in the
      mat. The mats are capable of light-dependent primary productivity as evidenced by
      13 C-bicarbonate photoassimilation. We also observed 13 C-bicarbonate
      photoassimilation in the presence of DCMU, an inhibitor of electron transfer to
      Photosystem II. Our results indicate that the mats carry out light-driven primary
      production in the absence of oxygen production-a mechanism that may have delayed
      the oxygenation of the Earth's oceans and atmosphere during the Proterozoic Eon.
      Furthermore, our observations of the production of 2-methyl hopanoids by
      Cyanobacteria under conditions of low oxygen and low light are consistent with
      the recovery of these structures from ancient black shales as well as their
      paucity in modern marine environments.

PMID- 29035023
TI  - When the Universe Gets Really Small.

PMID- 29035022
TI  - Microbial diversity and iron oxidation at Okuoku-hachikurou Onsen, a Japanese hot
      spring analog of Precambrian iron formations.
AB  - Banded iron formations (BIFs) are rock deposits common in the Archean and
      Paleoproterozoic (and regionally Neoproterozoic) sedimentary successions.
      Multiple hypotheses for their deposition exist, principally invoking the
      precipitation of iron via the metabolic activities of oxygenic,
      photoferrotrophic, and/or aerobic iron-oxidizing bacteria. Some isolated
      environments support chemistry and mineralogy analogous to processes involved in
      BIF deposition, and their study can aid in untangling the factors that lead to
      iron precipitation. One such process analog system occurs at Okuoku-hachikurou
      (OHK) Onsen in Akita Prefecture, Japan. OHK is an iron- and CO2 -rich,
      circumneutral hot spring that produces a range of precipitated mineral textures
      containing fine laminae of aragonite and iron oxides that resemble BIF fabrics.
      Here, we have performed 16S rRNA gene amplicon sequencing of microbial
      communities across the range of microenvironments in OHK to describe the
      microbial diversity present and to gain insight into the cycling of iron, oxygen,
      and carbon in this ecosystem. These analyses suggest that productivity at OHK is
      based on aerobic iron-oxidizing Gallionellaceae. In contrast to other BIF analog
      sites, Cyanobacteria, anoxygenic phototrophs, and iron-reducing micro-organisms
      are present at only low abundances. These observations support a hypothesis where
      low growth yields and the high stoichiometry of iron oxidized per carbon fixed by
      aerobic iron-oxidizing chemoautotrophs like Gallionellaceae result in
      accumulation of iron oxide phases without stoichiometric buildup of organic
      matter. This system supports little dissimilatory iron reduction, further setting
      OHK apart from other process analog sites where iron oxidation is primarily
      driven by phototrophic organisms. This positions OHK as a study area where the
      controls on primary productivity in iron-rich environments can be further
      elucidated. When compared with geological data, the metabolisms and mineralogy at
      OHK are most similar to specific BIF occurrences deposited after the Great
      Oxygenation Event, and generally discordant with those that accumulated before
      it.

PMID- 29035024
TI  - Half-Metallicity in Co-Doped WSe2 Nanoribbons.
AB  - The recent development of two-dimensional transition-metal dichalcogenides in
      electronics and optoelelectronics has triggered the exploration in spintronics,
      with high demand in search for half-metallicity in these systems. Here, through
      density functional theory (DFT) calculations, we predict robust half-metallic
      behaviors in Co-edge-doped WSe2 nanoribbons (NRs). With electrons partially
      occupying the antibonding state consisting of Co 3dyz and Se 4pz orbitals, the
      system becomes spin-polarized due to the defect-state-induced Stoner effect and
      the strong exchange splitting eventually gives rise to the half-metallicity. The
      half-metal gap reaches 0.15 eV on the DFT generalized gradient approximation
      level and increases significantly to 0.67 eV using hybrid functional.
      Furthermore, we find that the half-metallicity sustains even under large external
      strain and relatively low edge doping concentration, which promises the potential
      of such Co-edge-doped WSe2 NRs in spintronics applications.

PMID- 29035025
TI  - Substrate-Independent Ag-Nanoparticle-Loaded Hydrogel Coating with Regenerable
      Bactericidal and Thermoresponsive Antibacterial Properties.
AB  - We report a Ag-nanoparticle (AgNP)-based substrate-independent bactericidal
      hydrogel coating with thermoresponsive antibacterial property. To attach the
      hydrogel coating onto model substrate, we first coated ene-functionalized
      dopamine on the substrate, and then the hydrogel thin layer was formed on the
      surface via the UV light initiated surface cross-linking copolymerization of N
      isopropylacrylamide (NIPAAm) and sodium acrylate (AANa). Then, Ag ions were
      adsorbed into the hydrogel layers and reduced to AgNPs by sodium borohydride. The
      coating showed robust bactericidal ability against Escherichia coli and
      Staphylococcus aureus toward both contacted bacteria and the bacteria in the
      surrounding. Upon a reduction of the temperature below the LCST of PNIPAAm, the
      improved surface hydrophilicity and swollen PNIPAAm could detach the attached
      dead bacteria. Meanwhile, the long-lasting and regenerable antibacterial
      properties could be achieved by repeatedly loading AgNPs. By precisely
      controlling the AgNP loading amounts, the coating showed excellent
      hemocompatibility and no cytotoxity. Additionally, the coating could be applied
      to modify cell culture plate, since it could support cell adhesion and
      proliferation at 37  degrees C, while detach the cell by changing the temperature
      below lower critical solution temperature without the treatment of proteases. The
      study thus presents a promising way to fabricate thermoresponsive and regenerable
      antibacterial surfaces on diverse materials and devices for biomedical
      applications.

PMID- 29035026
TI  - Schottky Barrier Height of Pd/MoS2 Contact by Large Area Photoemission
      Spectroscopy.
AB  - MoS2, as a model transition metal dichalcogenide, is viewed as a potential
      channel material in future nanoelectronic and optoelectronic devices. Minimizing
      the contact resistance of the metal/MoS2 junction is critical to realizing the
      potential of MoS2-based devices. In this work, the Schottky barrier height (SBH)
      and the band structure of high work function Pd metal on MoS2 have been studied
      by in situ X-ray photoelectron spectroscopy (XPS). The analytical spot diameter
      of the XPS spectrometer is about 400 MUm, and the XPS signal is proportional to
      the detection area, so the influence of defect-mediated parallel conduction paths
      on the SBH does not affect the measurement. The charge redistribution by Pd on
      MoS2 is detected by XPS characterization, which gives insight into metal contact
      physics to MoS2 and suggests that interface engineering is necessary to lower the
      contact resistance for the future generation electronic applications.

PMID- 29035027
TI  - Heat-Treatment-Induced Compositional Evolution and Magnetic State Transition in
      Magnetic Chalcogenide Semiconductor GeFeTe without Structural Phase Change.
AB  - Control of magnetic properties in diluted magnetic semiconductors (DMSs) using
      external stimuli is a prerequisite for many spintronic applications. Fe-doped
      chalcogenide semiconductors are promising candidate materials for future
      spintronic devices since they offer the possibility of magnetic switching by
      their fast and reversible transition between amorphous and crystalline phases.
      However, for many proposed applications, magnetic manipulation in crystalline
      DMSs without a structural change is highly desirable. Thus, the ability to
      externally control the magnetism of magnetic chalcogenide semiconductors without
      structural phase change is of significance to enhance their application
      potential. Here we find that the annealing process could induce an
      antiferromagnetic (AFM)-ferromagnetic (FM) transition in magnetic chalcogenide
      semiconductor GeFeTe epilayers without deteriorating the crystal structure. The
      impact of heat treatment on magnetization in Ge1-xFexTe film depends on Fe
      concentration. The present data indicate that the AFM-FM transition originates
      from the evolution of Fe phase composition. This study gives an insight into the
      correlation between Fe phase composition, electronic structure, and magnetism in
      GeFeTe thin films.

PMID- 29035028
TI  - Stress-Mediated Enhancement of Ionic Conductivity in Fast-Ion Conductors.
AB  - Finding solid-state electrolytes with high ionic conductivity near room
      temperature is an important prerequisite for developing all-solid-state
      electrochemical batteries. Here, we investigate the effects of point defects
      (vacancies) and biaxial stress on the superionic properties of fast-ion
      conductors (represented by the archetypal compounds CaF2, Li-rich antiperovskite
      Li3OCl, and AgI) by using classical molecular dynamics and first-principles
      simulation methods. We find that the critical superionic temperature of all
      analyzed families of fast-ion conductors can be reduced by several hundreds of
      degrees through the application of relatively small biaxial stresses (|sigma| <=
      1 GPa) on slightly defective samples (cv ~ 1%). In AgI, we show that
      superionicity can be triggered at room temperature by applying a moderate
      compressive biaxial stress of ~1 GPa. In this case, we reveal the existence of a
      sigma-induced order-disorder phase transition involving sizable displacements of
      all the ions with respect to the equilibrium lattice that occurs prior to the
      stabilization of the superionic state. In CaF2 and Li3OCl, by contrast, we find
      that tensile biaxial stress (sigma < 0) favors ionic conductivity as due to an
      effective increase of the volume available to interstitial ions, which lowers the
      formation energy of Frenkel pair defects. Our findings provide valuable
      microscopic insight into the behavior of fast-ion conductors under mechanical
      constraints, showing that biaxial stress (or, conversely, epitaxial strain) can
      be used as an effective means to enhance ionic conductivity.

PMID- 29035029
TI  - Multilayer Ceramic Magnetoelectric Composites with Tailored Interfaces for
      Enhanced Response.
AB  - Composite materials consisting of two dissimilar ferroic phases are an excellent
      alternative to single-phase multiferroics for a wide range of magnetoelectric
      technologies. In composites with strain-mediated magnetoelectric coupling the
      response is strongly dependent on the characteristics of the interface between
      the two mechanically coupled phases. Among the different material approaches
      considered, cofired ceramic composites offer improved reliability in applications
      and are more adequate for free-forming and miniaturization. However, their
      magnetoelectric response often suffers from poor reproducibility, which has been
      reiteratively associated with the quality of the interfaces with little
      experimental support. Here, we report an in-depth study of the local material
      properties across the interfaces of 0.36BiScO3-0.64PbTiO3/NiFe2O4 multilayer
      ceramic composites, processed by spark plasma sintering of nanocrystalline
      powders. Tailored microstructures and low residual stress levels were obtained by
      adjusting the sintering mismatch between the two ferroic phases, which also
      resulted in fully functional interfaces and enhanced magnetoelectric responses.

PMID- 29035030
TI  - Effective Trapping of Lithium Polysulfides Using a Functionalized Carbon Nanotube
      Coated Separator for Lithium-Sulfur Cells with Enhanced Cycling Stability.
AB  - The critical issues that hinder the practical applications of lithium-sulfur
      batteries, such as dissolution and migration of lithium polysulfides, poor
      electronic conductivity of sulfur and its discharge products, and low loading of
      sulfur, have been addressed by designing a functional separator modified using
      hydroxyl-functionalized carbon nanotubes (CNTOH). Density functional theory
      calculations and experimental results demonstrate that the hydroxyl groups in the
      CNTOH provoked strong interaction with lithium polysulfides and resulted in
      effective trapping of lithium polysulfides within the sulfur cathode side. The
      reduction in migration of lithium polysulfides to the lithium anode resulted in
      enhanced stability of the lithium electrode. The conductive nature of CNTOH also
      aided to efficiently reutilize the adsorbed reaction intermediates for subsequent
      cycling. As a result, the lithium-sulfur cell assembled with a functional
      separator exhibited a high initial discharge capacity of 1056 mAh g-1
      (corresponding to an areal capacity of 3.2 mAh cm-2) with a capacity fading rate
      of 0.11% per cycle over 400 cycles at 0.5 C rate.

PMID- 29035031
TI  - Proximity Effect Induced Spin Injection in Phosphorene on Magnetic Insulator.
AB  - Black phosphorus is a promising candidate for future nanoelectronics with a
      moderate electronic band gap and a high carrier mobility. Introducing the
      magnetism into black phosphorus will widely expand its application scope and may
      present a bright prospect in spintronic nanodevices. Here, we report our first
      principles calculations of spin-polarized electronic structure of monolayer black
      phosphorus (phosphorene) adsorbed on a magnetic europium oxide (EuO) substrate.
      Effective spin injection into the phosphorene is realized by means of interaction
      with the nearby EuO(111) surface, i.e., proximity effect, which results in spin
      polarized electrons in the 3p orbitals of phosphorene, with the spin polarization
      at Fermi level beyond 30%, together with an exchange-splitting energy of ~0.184
      eV for conduction-band minimum of the adsorbed phosphorene corresponding to an
      energy region where only one spin channel is conductive. The energy region of
      these exchange-splitting and spin-polarized band gaps of the adsorbed phosphorene
      can be effectively modulated by in-plane strain. Intrinsically high and
      anisotropic carrier mobilities at the conduction-band minimum of the phosphorene
      also become spin-polarized mainly due to spin polarization of deformation
      potentials and are not depressed significantly after the adsorption. These
      extraordinary properties would endow black phosphorus with great potentials in
      the future spintronic nanodevices.

PMID- 29035032
TI  - Ultrathin Coaxial Fiber Supercapacitors Achieving High Energy and Power
      Densities.
AB  - Fiber-based supercapacitors have attracted significant interests because of their
      potential applications in wearable electronics. Although much progress has been
      made in recent years, the energy and power densities, mechanical strength, and
      flexibility of such devices are still in need of improvement for practical
      applications. Here, we demonstrate an ultrathin microcoaxial fiber supercapacitor
      (MUCFSC) with high energy and power densities (2.7 mW h/cm3 and 13 W/cm3), as
      well as excellent mechanical properties. The prototype with the smallest reported
      overall diameter (~13 MUm) is fabricated by successive coating of functional
      layers onto a single micro-carbon-fiber via a scalable process. Combining the
      simulation results via the electrochemical model, we attribute the high
      performance to the well-controlled thin coatings that make full use of the
      electrode materials and minimize the ion transport path between electrodes.
      Moreover, the MUCFSC features high bending flexibility and large tensile strength
      (more than 1 GPa), which make it promising as a building block for various
      flexible energy storage applications.

PMID- 29035033
TI  - Cross-Linking-Derived Synthesis of Porous CoxNiy/C Nanocomposites for Excellent
      Electromagnetic Behaviors.
AB  - The magnet/dielectric composites with tunable structure and composition have
      drawn much attention because of their particular merits in magnetoelectric
      properties compared with the sole dielectric or magnetic composites. In addition,
      porous materials at the nanoscale can satisfy the growing requirements in many
      industries. Therefore, constructing porous metal alloy/carbon nanocomposites is
      to be an admirable option. Unfortunately, traditional synthesis methods involve
      multistep routes and complicated insert-and-remove templates approaches. Here we
      report a facile process to synthesize CoxNiy/C composites via a spontaneous cross
      linking reaction and subsequent calcination process, during which multiple
      processes, including reducing polyvalent metal ions, forming alloy, and
      encapsulating alloy nanoparticles into porous carbon matrix, are achieved almost
      simultaneously. By adjusting the feed ratio of Co2+ to Ni2+ ions, controllable
      composition of CoxNiy/C composites can be gained. It should be noted that the
      CoxNiy/C composites are demonstrated to be excellent microwave absorbers from
      every aspect of assessment criteria including reflection loss, effective
      bandwidth, thickness, and weight of absorber. Our study opens up a promising
      technique for the synthesis of alloy/carbon composites with porous nanostructures
      with target functionalities.

PMID- 29035034
TI  - Ultrasmall MnO Nanoparticles Supported on Nitrogen-Doped Carbon Nanotubes as
      Efficient Anode Materials for Sodium Ion Batteries.
AB  - Sodium ion batteries (SIBs) have attracted increasing attentions as promising
      alternatives to lithium ion batteries (LIBs). Herein, we design and synthesize
      ultrasmall MnO nanoparticles (~4 nm) supported on nitrogen-doped carbon nanotubes
      (NDCT@MnO) as promising anode materials of SIBs. It is revealed that the
      carbonization temperature can greatly influence the structural features and thus
      the Na-storage behavior of the NDCT@MnO nanocomposites. The synergetic
      interaction between MnO and NDCT in the NDCT@MnO nanocomposites provides high
      rate capability and long-term cycling life due to high surface area, electrical
      conductivity, enhanced diffusion rate of Na+ ions, and prevented agglomeration
      and high stability of MnO nanoparticles. The resulting SIBs provide a high
      reversible specific capacity of 709 mAh g-1 at a current density of 0.1 A g-1 and
      a high capacity of 536 mAh g-1 almost without loss after 250 cycles at 0.2 A g-1.
      Even at a high current density of 5 A g-1, a capacity of 273 mAh g-1 can be
      maintained after 3000 cycles.

PMID- 29035035
TI  - Oxygen Vacancies and Stacking Faults Introduced by Low-Temperature Reduction
      Improve the Electrochemical Properties of Li2MnO3 Nanobelts as Lithium-Ion
      Battery Cathodes.
AB  - Among the Li-rich layered oxides Li2MnO3 has significant theoretical capacity as
      a cathode material for Li-ion batteries. Pristine Li2MnO3 generally has to be
      electrochemically activated in the first charge-discharge cycle which causes very
      low Coulombic efficiency and thus deteriorates its electrochemical properties. In
      this work, we show that low-temperature reduction can produce a large amount of
      structural defects such as oxygen vacancies, stacking faults, and orthorhombic
      LiMnO2 in Li2MnO3. The Rietveld refinement analysis shows that, after a reduction
      reaction with stearic acid at 340  degrees C for 8 h, pristine Li2MnO3 changes
      into a Li2MnO3-LiMnO2 (0.71/0.29) composite, and the monoclinic Li2MnO3 changes
      from Li2.04Mn0.96O3 in the pristine Li2MnO3 (P-Li2MnO3) to Li2.1Mn0.9O2.79 in the
      reduced Li2MnO3 (R-Li2MnO3), indicating the production of a large amount of
      oxygen vacancies in the R-Li2MnO3. High-resolution transmission electron
      microscope images show that a high density of stacking faults is also introduced
      by the low-temperature reduction. When measured as a cathode material for Li-ion
      batteries, R-Li2MnO3 shows much better electrochemical properties than P-Li2MnO3.
      For example, when charged-discharged galvanostatically at 20 mA.g-1 in a voltage
      window of 2.0-4.8 V, R-Li2MnO3 has Coulombic efficiency of 77.1% in the first
      charge-discharge cycle, with discharge capacities of 213.8 and 200.5 mA.h.g-1 in
      the 20th and 30th cycles, respectively. In contrast, under the same charge
      discharge conditions, P-Li2MnO3 has Coulombic efficiency of 33.6% in the first
      charge-discharge cycle, with small discharge capacities of 80.5 and 69.8 mA.h.g-1
      in the 20th and 30th cycles, respectively. These materials characterizations, and
      electrochemical measurements show that low-temperature reduction is one of the
      effective ways to enhance the performances of Li2MnO3 as a cathode material for
      Li-ion batteries.

PMID- 29035036
TI  - Nanoprobe Synthesized by Magnetotactic Bacteria, Detecting Fluorescence
      Variations under Dissociation of Rhodamine B from Magnetosomes following
      Temperature, pH Changes, or the Application of Radiation.
AB  - We report a method of fabrication of fluorescent magnetosomes, designated as
      MCR400, in which 400 MUM of rhodamine B are introduced in the growth medium of
      AMB-1 magnetotactic bacteria and fluorescent magnetosomes are then extracted from
      these bacteria. These fluorescent magnetosomes behave differently from most
      fluorescent nanoprobes, which often lead to fluorescence losses over time due to
      photobleaching. Indeed, when MCR400 are heated to 30-90  degrees C, brought to an
      acidic pH, or exposed to radiations, we observed that their fluorescence
      intensity increased. We attributed this behavior to the dissociation of rhodamine
      B from the magnetosomes. Interestingly, enhanced fluorescence was also observed
      in vitro when MCR400 were mixed with either primary macrophages or tumor cells
      (TC1-GFP or RG2-Cells) or in vivo when MCR400 were introduced in rat
      glioblastoma. We showed that MCR400 internalize in tumor and immune cells
      (macrophages) leading to enhanced fluorescence, suggesting that fluorescent
      magnetosomes could be used during cancer treatments such as magnetic hyperthermia
      to image cells of interest such as immune or tumor cells.

PMID- 29035037
TI  - Controlling Superwettability by Microstructure and Surface Energy Manipulation on
      Three-Dimensional Substrates for Versatile Gravity-Driven Oil/Water Separation.
AB  - Superwettable materials have gained tremendous attention because of their special
      wetting abilities. The key to obtaining and tuning superwettability is to
      precisely control the interfacial microstructures and surface energies of
      materials. Herein, we propose a novel approach to controlling the
      superwettability of three-dimensional foams. The surface microstructure was
      manipulated by the layer-by-layer covalent grafting of multidimensional
      nanoparticles (e.g., silica, carbon nanotubes, and graphene oxide), and the
      surface energy was tailored by grafting chemicals with different functional
      groups. This grafting approach improved the mechanical performance, reduced
      particle loading, and prevented particle disassociation, thereby increasing the
      absorption capacity and durability of the functionalized foams. More importantly,
      superhydrophobic/superoleophilic foams were obtained after heptanol grafting.
      They showed water contact angles of 153 degrees  in air and 158 degrees  in oil,
      an absorption capacity 113 times their weight gain, and a remarkable flux of 32.6
      L m-2 s-1 for the separation of oil from water driven by gravity. Polydopamine
      grafting resulted in superhydrophilic/underwater superoleophobic foams that had
      an oil contact angle of 152 degrees  under water and a high flux of 19.3 L m-2 s
      1 for the separation of water from oil. Thus, this study offers not only
      intelligent materials for versatile oil/water separation but also a profound
      approach for engineering high-performance superwettable materials.

PMID- 29035038
TI  - Dynamics and Morphology of Nanoparticle-Linked Polymers Elucidated by Nuclear
      Magnetic Resonance.
AB  - Nanoparticles are frequently modified with polymer layers to control their
      physical and chemical properties, but little is understood about the morphology
      and dynamics of these polymer layers. We report here an NMR-based investigation
      of a model polymer-modified nanoparticle, using multiple NMR techniques including
      1H NMR, diffusion-ordered spectroscopy (DOSY), total correlation spectroscopy
      (TOCSY), and T2 relaxometry to characterize the dynamics of the nanoparticle
      polymer interface. Using 5 nm detonation nanodiamond covalently linked to
      poly(allylamine) hydrochloride as a model system, we demonstrate the use of NMR
      to distinguish between free and bound polymer and to characterize the degree to
      which the segments of the nanoparticle-wrapping polymer are mobile (loops and
      tails) versus immobile (trains). Our results show that the polymer-wrapped
      nanoparticle contains a large fraction of highly mobile polymer segments,
      implying that the polymer extends well into solution away from the nanoparticle
      surface. Flexible, distal polymer segments are likely to be more accessible to
      extended objects such as cell membranes, compared with polymer segments that are
      in close proximity to the nanoparticle surface. Thus, these flexible segments may
      be particularly important in controlling subsequent interactions of the
      nanoparticles. While reported here for a model system, the methodology used
      demonstrates how NMR methods can provide important insights into the structure
      and dynamics at nanoparticle-polymer interfaces, leading to new perspectives on
      the behavior and interactions of polymer-functionalized nanoparticles in aqueous
      systems.

PMID- 29035039
TI  - Synthesis of Water-Dispersible Mn2+ Functionalized Silicon Nanoparticles under
      Room Temperature and Atmospheric Pressure for Fluorescence and Magnetic Resonance
      Dual-Modality Imaging.
AB  - Silicon nanoparticles (Si NPs) have been widely used in fluorescence imaging.
      However, rigorous synthesis conditions and the single modality imaging limit the
      further development of Si NPs in the field of biomedical imaging. Here, we
      reported a method for synthesizing water-dispersible Mn2+ functionalized Si NPs
      (Mn-Si NPs) under mild experimental conditions for fluorescence and magnetic
      resonance dual-modality imaging. The whole synthesis process was completed under
      room temperature and atmospheric pressure, and no special and expensive equipment
      was required. The synthetic nanoparticles, with favorable pH stability, NaCl
      stability, photostability, and low toxicity, emitted green fluorescence (512 nm).
      At the same time, the nanoparticles also demonstrated excellent magnetic
      resonance imaging ability. In vitro, their T1-weighted magnetic resonance imaging
      effect was obvious, and the value of longitudinal relaxation degree r1 reached
      4.25 mM-1 s-1. On the basis of their good biocompatibility, Mn-Si NPs were
      successfully used for the fluorescence imaging as well as magnetic resonance
      imaging in vivo.

PMID- 29035040
TI  - Orally Administered Baker's Yeast beta-Glucan Promotes Glucose and Lipid
      Homeostasis in the Livers of Obesity and Diabetes Model Mice.
AB  - Baker's yeast glucan (BYG) has been reported to be an anti-diabetic agent. In the
      work described herein, further study on the effect of orally administered BYG on
      glucose and lipid homeostasis in the livers of ob/ob mice was performed. It was
      found that BYG decreased the blood glucose and the hepatic glucose and lipid
      disorders. Western blotting analysis revealed that BYG up-regulated p-AKT and p
      AMPK, and down-regulated p-Acc in the liver. Furthermore, RNA-Seq analysis
      indicated that BYG down-regulated genes responsible for gluconeogenesis (G6pase
      and Got1), fatty acid biosynthesis (Acly, Acc, Fas, etc.), glycerolipid synthesis
      (Gpam and Lipin1/2), and cholesterol synthesis (Hmgcr, Fdps, etc.). Additionally,
      BYG decreased glucose transporters SGLT1 and GLUT2, fat emulsification, and
      adipogenic genes/proteins in the intestine to decrease glucose and lipid
      absorption. All these findings demonstrated that BYG is beneficial for regulating
      glucose and lipid homeostasis in diabetic mice, and thus has potential
      applications in anti-diabetic foods or drugs.

PMID- 29035041
TI  - Purification and Characterization of a Novel beta-Cypermethrin-Degrading
      Aminopeptidase from Pseudomonas aeruginosa GF31.
AB  - In this study, a novel beta-cypermethrin-degrading enzyme was isolated and
      purified by 32.8 fold from the extracellular cell-free filtrate of Pseudomonas
      aeruginosa GF31with the protein recovery of 26.6%. The molecular mass of the
      enzyme was determined to be 53 kDa. The optimum temperature for the activity was
      surprisingly 60  degrees C, and moreover, the purified enzyme showed a good pH
      stability, maintaining over 85% of its initial activity in the pH 5.0-9.0 range.
      Most of the common metal ions exhibited little influence on the activity except
      for Hg2+, Ag+, and Cu2+. After the complete gene sequence of the degrading enzyme
      was obtained by subcloning, sequence analyses as well as enzymatic properties
      demonstrated that the islolated enzyme should be an aminopeptidase. This is the
      first reported aminopeptidase for pyrethroid hydrolase, providing new potential
      enzyme resources for the degradation of this type of pesticide.

PMID- 29035042
TI  - nmrML: A Community Supported Open Data Standard for the Description, Storage, and
      Exchange of NMR Data.
AB  - NMR is a widely used analytical technique with a growing number of repositories
      available. As a result, demands for a vendor-agnostic, open data format for long
      term archiving of NMR data have emerged with the aim to ease and encourage
      sharing, comparison, and reuse of NMR data. Here we present nmrML, an open XML
      based exchange and storage format for NMR spectral data. The nmrML format is
      intended to be fully compatible with existing NMR data for chemical, biochemical,
      and metabolomics experiments. nmrML can capture raw NMR data, spectral data
      acquisition parameters, and where available spectral metadata, such as chemical
      structures associated with spectral assignments. The nmrML format is compatible
      with pure-compound NMR data for reference spectral libraries as well as NMR data
      from complex biomixtures, i.e., metabolomics experiments. To facilitate format
      conversions, we provide nmrML converters for Bruker, JEOL and Agilent/Varian
      vendor formats. In addition, easy-to-use Web-based spectral viewing, processing,
      and spectral assignment tools that read and write nmrML have been developed.
      Software libraries and Web services for data validation are available for tool
      developers and end-users. The nmrML format has already been adopted for capturing
      and disseminating NMR data for small molecules by several open source data
      processing tools and metabolomics reference spectral libraries, e.g., serving as
      storage format for the MetaboLights data repository. The nmrML open access data
      standard has been endorsed by the Metabolomics Standards Initiative (MSI), and we
      here encourage user participation and feedback to increase usability and make it
      a successful standard.

PMID- 29035043
TI  - Remarkable Reactivity Differences between Glucosides with Identical Leaving
      Groups.
AB  - Two isomeric aryl 2-deoxy-2-fluoro-beta-glucosides react with a beta-glucosidase
      at rates differing by 106-fold, despite the fact that they release the same
      aromatic aglycone. In contrast, the equivalent glucoside substrates react with
      essentially identical rate constants. Insight into the source of these surprising
      rate differences was obtained through a comprehensive study of the nonenzymatic
      (spontaneous) hydrolysis of these same substrates, wherein an approximate 105
      fold difference in rates was measured, clarifying that the differences were
      inherent rather than being due to specific interactions with the enzyme. The
      possibility that an alternate nucleophilic aryl substitution mechanism was
      responsible for the rapid reaction of the faster substrate was excluded through
      18O-labeling studies. Further exploration of the origins of these rate
      differences involved analysis of X-ray crystal structures as well as quantum
      chemical calculations, which surprisingly revealed that ground state
      destabilization and transition state stabilizing effects contribute almost
      equally to the observed reactivity differences. These studies highlight the
      dangers of using simple reference equilibria such as pKa values as measures of
      leaving group ability.

PMID- 29035045
TI  - Energy and Biocides Storage Compounds: Synthesis and Characterization of
      Energetic Bridged Bis(triiodoazoles).
AB  - Energetic bridged triiodopyrazoles and triiodoimidazoles were designed and
      synthsized by reacting potassium triiodopyrazolate or triiodoimidazolate with
      corresponding dichloro compounds. All compounds were fully characterized by 1H
      and 13C NMR spectroscopy, IR spectroscopy, and elemental analyses. The structure
      of compound 1 was further confirmed by single-crystal X-ray diffraction. All of
      the compounds exhibit good thermal stability with decomposition temperatures
      between 199 and 270  degrees C and high densities ranging from 2.804 to 3.358
      g/cm3. The detonation performances and the detonation products were calculated by
      CHEETAH 7. Compound 3 (Dv = 4765 m s-1; P = 17.9 GPa) and compound 7 (Dv = 4841 m
      s-1; P = 18.5 GPa) show comparable detonation pressure to TNT, and high iodine
      content makes them promising as energy and biocides storage compounds.

PMID- 29035044
TI  - Nicotine Alters the Gut Microbiome and Metabolites of Gut-Brain Interactions in a
      Sex-Specific Manner.
AB  - As the primary active substance in tobacco, nicotine affects the activity of the
      central nervous system, and its effects are sex-dependent. There are complex
      interactions between the gut and brain, and the gut microbiome can influence
      neuronal activity and host behavior, with diverse chemical signaling being
      involved. However, it is unclear whether nicotine can affect the normal gut
      microbiome and associated chemical signaling of the gut-brain axis. Sex is an
      important factor that shapes the gut microbiome, but the role of sex in the
      interaction among nicotine, gut bacteria, and related metabolites remains
      unknown. In this study, we applied high-throughput sequencing and gas
      chromatography-mass spectrometry (GC-MS) to explore how nicotine exposure affects
      the gut microbiome and its metabolism in female and male C57BL/6J mice, with a
      focus on the chemical signaling involved in gut-brain interactions. 16S
      sequencing results indicated that the community composition of the gut microbiome
      was differentially perturbed by nicotine in females and males. Differential
      alterations of bacterial carbohydrate metabolic pathways are consistent with
      lower body weight gain in nicotine-treated males. Oxidative stress response and
      DNA repair genes were also specifically enriched in the nicotine-treated male gut
      microbiome. The fecal metabolome indicated that multiple neurotransmitters, such
      as glutamate, gamma-aminobutyric acid (GABA), and glycine, were differentially
      altered in female and male mice. Some neuroactive metabolites, including leucine
      and uric acid, were also changed. This study demonstrates a sex-dependent effect
      of nicotine on gut microbiome community composition, functional bacterial genes,
      and the fecal metabolome.

PMID- 29035046
TI  - Viscosity of Water Interfaces with Hydrophobic Nanopores: Application to Water
      Flow in Carbon Nanotubes.
AB  - The nanoconfinement of water results in changes in water properties and
      nontraditional water flow behaviors. The determination of the interfacial
      interactions between water and hydrophobic surfaces helps in understanding many
      of the nontraditional behaviors of nanoconfined water. In this study, an approach
      for the identification of the viscosity of water interfaces with hydrophobic
      nanopores as a function of the nanopore diameter and water-solid (nanopore)
      interactions is proposed. In this approach, water in a hydrophobic nanopore is
      represented as a double-phase water with two distinct viscosities: water
      interface and water core. First, the slip velocity to pressure gradient ratio of
      water flow in hydrophobic nanopores is obtained via molecular dynamics (MD)
      simulations. Then the water interface viscosity is determined via a pressure
      gradient-based bilayer water flow model. Moreover, the core viscosity and the
      effective viscosity of water flow in hydrophobic nanopores are derived as
      functions of the nanopore diameter and water-solid interactions. This approach is
      utilized to report the interface viscosity, core viscosity, and effective
      viscosity of water flow in carbon nanotubes (CNTs) as functions of the CNT
      diameter. Moreover, using the proposed approach, the transition from MD to
      continuum mechanics is revealed where the bulk water properties are recovered for
      large CNTs.

PMID- 29035047
TI  - Electrocatalytic Water Oxidation by a Water-Soluble Copper(II) Complex with a
      Copper-Bound Carbonate Group Acting as a Potential Proton Shuttle.
AB  - Water-soluble copper(II) complexes of the dianionic tridentate pincer ligand N,N'
      2,6-dimethylphenyl-2,6-pyridinedicarboxamidate (L) are catalysts for water
      oxidation. In [L-CuII-DMF] (1, DMF = dimethylformamide) and [L-CuII-OAc]- (2, OAc
      = acetate), ligand L binds CuII through three N atoms, which define an equatorial
      plane. The fourth coordination site of the equatorial plane is occupied by DMF in
      1 and by OAc- in 2. These two complexes can electrocatalyze water oxidation to
      evolve O2 in 0.1 M pH 10 carbonate buffer. Spectroscopic, titration, and
      crystallographic studies show that both 1 and 2 undergo ligand exchange when they
      are dissolved in carbonate buffer to give [L-CuII-CO3H]- (3). Complex 3 has a
      similar structure as those of 1 and 2 except for having a carbonate group at the
      fourth equatorial position. A catalytic cycle for water oxidation by 3 is
      proposed based on experimental and theoretical results. The two-electron oxidized
      form of 3 is the catalytically active species for water oxidation. Importantly,
      for these two oxidation events, the calculated potential values of Ep,a = 1.01
      and 1.59 V vs normal hydrogen electrode (NHE) agree well with the experimental
      values of Ep,a = 0.93 and 1.51 V vs NHE in pH 10 carbonate buffer. The potential
      difference between the two oxidation events is 0.58 V for both experimental and
      calculated results. With computational evidence, this Cu-bound carbonate group
      may act as a proton shuttle to remove protons for water activation, a key role
      resembling intramolecular bases as reported previously.

PMID- 29035048
TI  - Structural Sequencing of Oligopeptides Aided by 1H Iterative Full-Spin Analysis.
AB  - This report describes an approach using 1H NMR iterative full-spin analysis
      (HiFSA) to extract definitive structural information on unknown peptides from 1D
      1H NMR data. By comparing the experimental data and HiFSA fingerprint of a known
      analogue, it is possible to isolate the characteristic 1H subspectrum of the
      different amino acids and, thus, elucidate the structure of the peptide. To
      illustrate this methodology, a comprehensive analysis of five new anti
      Mycobacterium tuberculosis peptides (2-6), all analogues of ecumicin (1), was
      carried out. The method was validated by demonstrating congruence of the HiFSA
      based structures with all available data, including MS and 2D NMR. The highly
      reproducible HiFSA fingerprints of the new ~1600 amu peptides were generated in
      this process. Besides oligo-peptides, the HiFSA sequencing approach could be
      extended to all oligomeric compounds consisting of chains of monomers lacking H-H
      spin-spin coupling across the moieties. HiFSA sequencing is capable of
      differentiating complex oligomers that exhibit minor structural differences such
      as shifted hydoxyl or methyl groups. Because it employs the basic and most
      sensitive 1D 1H NMR experiment, HiFSA sequencing enables the exploration of
      peptide analogues up to at least 2000 amu, even with basic contemporary
      spectrometers and when only sub-milligram amounts of isolates are available.

PMID- 29035049
TI  - Exceptionally High Proton and Lithium Cation Gas-Phase Basicity of the Anti
      Diabetic Drug Metformin.
AB  - Substituted biguanides are known for their biological effect, and a few of them
      are used as drugs, the most prominent example being metformin (1,1
      dimethylbiguanide, IUPAC name: N,N-dimethylimidodicarbonimidic diamide). Because
      of the presence of hydrogen atoms at the amino groups, biguanides exhibit a
      multiple tautomerism. This aspect of their structures was examined in detail for
      unsubstituted biguanide and metformin in the gas phase. At the density functional
      theory (DFT) level {essentially B3LYP/6-311+G(d,p)}, the most stable structures
      correspond to the conjugated, push-pull, system (NR2)(NH2)C?N-C(?NH)NH2 (R = H,
      CH3), further stabilized by an internal hydrogen bond. The structural and
      energetic aspects of protonation and lithium cation adduct formation of biguanide
      and metformin was examined at the same level of theory. The gas-phase protonation
      energetics reveal that the more stable tautomer is protonated at the terminal
      imino C?NH site, still with an internal hydrogen bond maintaining the structure
      of the neutral system. The calculated proton affinity and gas-phase basicity of
      the two molecules reach the domain of superbasicity. By contrast, the lithium
      cation prefers to bind the less stable, not fully conjugated, tautomer
      (NR2)C(?NH)-NH-C(?NH)NH2 of biguanides, in which the two C?NH groups are
      separated by NH. This less stable form of biguanides binds Li+ as a bidentate
      ligand, in agreement with what was reported in the literature for other metal
      cations in the solid phase. The quantitative assessment of resonance in
      biguanide, in metformin and in their protonated forms, using the HOMED and HOMA
      indices, reveals an increase in electron delocalization upon protonation. On the
      contrary, the most stable lithium cation adducts are less conjugated than the
      stable neutral biguanides, because the metal cation is better coordinated by the
      not-fully conjugated bidentate tautomer.

PMID- 29035050
TI  - Cu(I) Coordination Polymers as the Green Heterogeneous Catalysts for Direct C-H
      Bonds Activation of Arylalkanes to Ketones in Water with Spatial Confinement
      Effect.
AB  - To develop coordination polymers (CPs) as catalysts to selectively catalyze the
      reaction of C-H bond activation of arylalkanes to their homologous ketones, three
      new Cu(I)-based coordination polymers (CuI-CPs) [CuI(aas-TPB)]n (1), [CuBr(ass
      TPB)CH3CN]n (2), and {[Cu(ass-TPB)]Cl}n (3) (TPB = N,N,N-tris(3-pyridinyl)-1,3,5
      benzenetricarboxamide) were synthesized. Structural variations from a herringbone
      fashion one-dimensional framework of 1 to a two-dimensional framework of 2
      containing a 48-membered macrocycle and a cationic three-dimensional framework of
      3 filled with Cl- anions were observed arising from the different halogen ions (I
      , Br-, and Cl-). 1-3 were used as the green heterogeneous catalysts to catalyze
      direct C-H bond activation reactions of arylalkanes to ketones under mild
      reaction conditions with water as solvent. Handy product separation, convenient
      reaction procedures, and recyclability of these catalysts make the catalytic
      system fascinating. Moreover, the CuI-CPs performed the reaction with high
      regioselectivity due to the unique spatial confinement effect of CPs.

PMID- 29035051
TI  - Integrating Carbamylation and Ultraviolet Photodissociation Mass Spectrometry for
      Middle-Down Proteomics.
AB  - The most popular bottom-up proteomics workflow uses trypsin to enzymatically
      cleave proteins C-terminal to lysine and arginine residues prior to LCMS/MS
      analysis of the resulting peptides. The high frequency of these residues
      generates short peptides, some of which are too small or uninformative for
      optimal analysis and which potentially contribute to gaps in sequence coverage of
      proteins. Analysis of larger peptides, termed "middle-down", has the potential to
      span greater sections of protein sequences if the larger peptides are adequately
      characterized based on their fragmentation patterns. We describe a strategy to
      generate larger peptides in conjunction with successful characterization by
      ultraviolet photodissociation (UVPD) for MS/MS analysis in a middle-down
      workflow, as demonstrated for proteins from E. coli lysates. The larger peptides
      are produced via modification of lysine residues by carbamylation of proteins.
      Carbamylation of proteins followed by tryptic digestion produced peptides similar
      to those expected from Arg-C proteolysis, yet with fewer missed and nonspecific
      cleavages. UVPD provides excellent sequence coverage of the larger peptides that
      are often less well characterized by traditional collision-based activation
      methods.

PMID- 29035052
TI  - Filling the Missing Links of M3n Prototype 3d-4f and 4f Cyclic Coordination
      Cages: Syntheses, Structures, and Magnetic Properties of the Ni10Ln5 and the Er3n
      Wheels.
AB  - In this paper, we proposed a number rule for 3d-4f and 4f cyclic coordination
      cages (CCCs); that is, CCCs consisting of vertex-sharing M4(MU3-OH)4 (M = 3d
      transition metal or 4f lanthanide ions) units should have 3 * n metal centers
      (abbreviated M3n), where n represents the number of the M4(MU3-OH)4 subunits.
      Under this number rule we reasoned that some species of CCCs, for example, the
      pentadecanuclear 3d-4f wheel and the pure 4f wheels with 9 or 18 centers, should
      practically have existed. However, there are no such complexes reported in the
      literature. To realize such CCCs we employed a mixed-ligand approach, that is, to
      simultaneously use the primary and the ancillary ligands for syntheses. This
      approach successfully leads to the isolation of two families of CCCs, namely, the
      Ni10Ln5 (Ln = Gd and Y) mixed-metal wheels and the Er3n (n = 4, 5, and 6) pure 4f
      metal wheels. These two families of CCCs unambiguously fill the missing links of
      the M3n prototype CCCs. Moreover, dominated ferromagnetic interaction indicates
      high ground-spin state for the Gd5Ni10 wheel. The ferromagnetic interactions
      between the nickel centers are verified using the diamagnetic Y(III) analogue,
      which reveals an averaged coupling constant (J = 2.7 cm-1), while accompanied by
      a large negative zero-field splitting parameter (D = -6.1 cm-1) for single Ni(II)
      ions. Interestingly, the Y(III)-diluted Er12 wheel shows slow magnetic relaxation
      behavior, presumably indicating the magnetically anisotropic nature of the
      erbium(III) ions.

PMID- 29035053
TI  - Designed Bifunctional Phosphine Ligand-Enabled Gold-Catalyzed Isomerizations of
      Ynamides and Allenamides: Stereoselective and Regioselective Formation of 1-Amido
      1,3-dienes.
AB  - By using designed biphenyl-2-ylphosphines functionalized with a remote basic
      groups as ligands, N-alkynyl-o-nosylamides are directly converted to (1E,3E)-1
      amido-1,3-dienes with excellent diastereoselectivities under gold catalysis. With
      allenamides as substrates, the gold-catalyzed isomerizations are high yielding
      and applicable to a broad substrate scope including various nitrogen protecting
      groups and exhibit unprecedented (3E)-selectivities for the distal C-C double
      bond and good regioselectivities. Combining this gold catalysis with one-pot
      Diels-Alder reactions leads to rapid assembly of valuable bicyclic compounds.

PMID- 29035054
TI  - Quantum Yields of Nitrite (NO2-) from the Photolysis of Nitrate (NO3-) in Ice at
      313 nm.
AB  - Photochemical reactions of nitrate in snow release reactive nitrogen species via
      two channels, which produce (1) nitrogen dioxide (NO2) and hydroxyl radical (*OH)
      and (2) nitrite (NO2-) and oxygen atom (O(3P)). Quantum yields (Phi) for these
      channels are generally well characterized, except for channel 2 in ice. In this
      study, we quantify Phi(NO2-) in water ices and examine the impacts of pH and
      organic scavengers of *OH. Compared to solution results, we find that nitrite
      quantum yields in ice are more sensitive to pH and that *OH scavengers are less
      effective, although 2-propanol appears to work well. The temperature dependence (
      30 to 25  degrees C) of Phi(NO2-) in samples containing 2-propanol is well
      described by a single regression line, ln(Phi(NO2-)) = -(1330 +/- 100)(1/T(K)) +
      (0.09 +/- 0.39). At -10  degrees C, the resulting quantum yield is 4.6 times
      larger than the previously reported (and recommended) value without an *OH
      scavenger. Although some reports suggest nitrite is a minor product from nitrate
      photolysis, based on our current and past results, rates of photoproduction of
      NO2- and NO2 are similar at room temperature, while NO2- production dominates at
      lower temperatures in solution and ice.

PMID- 29035055
TI  - Atmospheric Simulation Chamber Studies of the Gas-Phase Photolysis of Pyruvic
      Acid.
AB  - Pyruvic acid is an atmospherically abundant alpha-keto-acid that degrades
      efficiently from the troposphere via gas-phase photolysis. To explore conditions
      relevant to the environment, 2-12 ppm pyruvic acid is irradiated by a solar
      simulator in the environmental simulation chamber, CESAM. The combination of the
      long path length available in the chamber and its low surface area to volume
      ratio allows us to quantitatively examine the quantum yield and photochemical
      products of pyruvic acid. Such details are new to the literature for the low
      initial concentrations of pyruvic acid employed here. We determined photolysis
      quantum yields of phiobsN2 = 0.84 +/- 0.1 in nitrogen and phiobsAir = 3.2 +/- 0.5
      in air, which are higher than those reported by previous studies that used higher
      partial pressures of pyruvic acid. The quantum yield greater than unity in air is
      due to secondary chemistry, driven by O2, that emerges under the conditions in
      these experiments. The low concentration of pyruvic acid and the resulting oxygen
      effect also alter the product distribution such that acetic acid, rather than
      acetaldehyde, is the primary product in air. These results indicate that
      tropospheric pyruvic acid may degrade in part via photoinduced mechanisms that
      are different than previously expected.

PMID- 29035056
TI  - Coupling Reaction of Cu-Based Carbene and Nitroso Radical: A Tandem Reaction To
      Construct Isoxazolines.
AB  - In this letter, an unprecedented cross-coupling reaction between copper carbene
      and nitroso radical has been developed. This radical-carbene coupling reaction
      (RCC reaction) offers a novel approach for the preparation of various
      isoxazolines, which features the construction of C-C, C-O, and C?N bonds in a one
      pot process. The synthetic utility of our method is further enhanced by its mild
      reaction conditions, wide substrate scope, and simple procedures.

PMID- 29035057
TI  - Freeze-Dried Sulfur-Graphene Oxide-Carbon Nanotube Nanocomposite for High Sulfur
      Loading Lithium/Sulfur Cells.
AB  - The ambient-temperature rechargeable lithium/sulfur (Li/S) cell is a strong
      candidate for the beyond lithium ion cell since significant progress on
      developing advanced sulfur electrodes with high sulfur loading has been made.
      Here we report on a new sulfur electrode active material consisting of a
      cetyltrimethylammonium bromide-modified sulfur-graphene oxide-carbon nanotube (S
      GO-CTA-CNT) nanocomposite prepared by freeze-drying. We show the real-time
      formation of nanocrystalline lithium sulfide (Li2S) at the interface between the
      S-GO-CTA-CNT nanocomposite and the liquid electrolyte by in situ TEM observation
      of the reaction. The combination of GO and CNT helps to maintain the structural
      integrity of the S-GO-CTA-CNT nanocomposite during lithiation/delithiation. A
      high S loading (11.1 mgS/cm2, 75% S) S-GO-CTA-CNT electrode was successfully
      prepared using a three-dimensional structured Al foam as a substrate and showed
      good S utilization (1128 mAh/g S corresponding to 12.5 mAh/cm2), even with a very
      low electrolyte to sulfur weight ratio of 4. Moreover, it was demonstrated that
      the ionic liquid in the electrolyte improves the Coulombic efficiency and
      stabilizes the morphology of the Li metal anode.

PMID- 29035058
TI  - Singlet Fission and Excimer Formation in Disordered Solids of Alkyl-Substituted
      1,3-Diphenylisobenzofurans.
AB  - We describe the preparation and excited state dynamics of three alkyl derivatives
      of 1,3-diphenylisobenzofuran (1) in both solutions and thin films. The
      substitutions are intended to disrupt the slip-stacked packing observed in
      crystals of 1 while maintaining the favorable energies of singlet and triplet for
      singlet fission (SF). All substitutions result in films that are largely
      amorphous as judged by the absence of strong X-ray diffraction peaks. The films
      of 1 carrying a methyl in the para position of one phenyl ring undergo SF
      relatively efficiently (>=75% triplet yield, PhiT) but more slowly than thin
      films of 1. When the methyl is replaced with a t-butyl, kinetic competition in
      the excited state favors excimer formation rather than SF (PhiT = 55%). When t-Bu
      groups are placed in both meta positions of the phenyl substituent, SF is slowed
      further and PhiT = 35%.

PMID- 29035059
TI  - ZnO Nanomembrane/Expanded Graphite Composite Synthesized by Atomic Layer
      Deposition as Binder-Free Anode for Lithium Ion Batteries.
AB  - A zinc oxide (ZnO)/expanded graphite (EG) composite was successfully synthesized
      by using atomic layer deposition with dimethyl zinc as the zinc source and
      deionized water as the oxidant source. In the composite structure, EG provides a
      conductive channel and mechanical support to ZnO nanomembranes, which effectively
      avoids the electrode pulverization caused by the volume change of ZnO. The anodes
      made from the flexible composite films without using binder, conductive agent,
      and current collector show high stable capacities especially for that with a
      moderate ZnO concentration. The highest capacity stayed at 438 mAh g-1 at a
      current rate of 200 mA g-1 after 500 cycles. The good performance is considered
      to be due to the co-effects of the high capacity of ZnO and the support of the EG
      framework. Such composite structures may have great potential in low-cost and
      flexible batteries.

PMID- 29035060
TI  - A Computational Study Investigating the Energetics and Kinetics of the HNCO +
      (CH3)2NH Reaction Catalyzed by a Single Water Molecule.
AB  - High-level ab initio calculations are used to explore the energetics and kinetics
      for the formation of 1,1-dimethyl urea via the reaction of isocyanic acid (HNCO)
      with dimethyl amine (DMA) catalyzed by a single water molecule. Compared to the
      uncatalyzed HNCO + DMA reaction, the presence of a water molecule lowers the
      reaction barrier, defined here as the energy difference between the separated
      HNCO + DMA + H2O reactants and the transition state (TS), by ~26 kcal/mol. In
      addition to the HNCO + DMA + H2O reaction, the energetics of the analogous
      reactions involving, respectively, ammonia and methyl amine were also
      investigated. Comparing the barriers for these three amine addition reactions,
      which can be represented as HNCO + R-NH-R' + H2O with R and R' being either -CH3
      or -H, we find that the reaction barrier decreases with the degree of methylation
      on the amine nitrogen atom. The effective rate constants for the bimolecular
      reaction pathways HNCO..H2O + DMA and HNCO..DMA + H2O were calculated using
      canonical variational TS theory coupled with both small curvature and zero
      curvature tunneling corrections over the 200-300 K temperature range. For
      comparison, we also calculated the rate constant for the HNCO + OH reaction. Our
      results suggest that the HNCO + H2O + DMA reaction can make a non-negligible
      contribution to the gas-phase removal of atmospheric HNCO under conditions where
      the HNCO and water concentrations are high and the temperature is low.

PMID- 29035061
TI  - Terahertz Nanofocusing with Cantilevered Terahertz-Resonant Antenna Tips.
AB  - We developed THz-resonant scanning probe tips, yielding strongly enhanced and
      nanoscale confined THz near fields at their tip apex. The tips with length in the
      order of the THz wavelength (lambda = 96.5 MUm) were fabricated by focused ion
      beam (FIB) machining and attached to standard atomic force microscopy (AFM)
      cantilevers. Measurements of the near-field intensity at the very tip apex (25 nm
      radius) as a function of tip length, via graphene-based (thermoelectric) near
      field detection, indicate their first and second order geometrical antenna
      resonances for tip length of 33 and 78 MUm, respectively. On resonance, we find
      that the near-field intensity is enhanced by one order of magnitude compared to
      tips of 17 MUm length (standard AFM tip length), which is corroborated by
      numerical simulations that further predict remarkable intensity enhancements of
      about 107 relative to the incident field. Because of the strong field enhancement
      and standard AFM operation of our tips, we envision manifold and straightforward
      future application in scattering-type THz near-field nanoscopy and THz
      photocurrent nanoimaging, nanoscale nonlinear THz imaging, or nanoscale control
      and manipulation of matter employing ultrastrong and ultrashort THz pulses.

PMID- 29035062
TI  - Determination of the Complete Spin Density Distribution in 13C-Labeled Protein
      Bound Radical Intermediates Using Advanced 2D Electron Paramagnetic Resonance
      Spectroscopy and Density Functional Theory.
AB  - Determining the complete electron spin density distribution for protein-bound
      radicals, even with advanced pulsed electron paramagnetic resonance (EPR)
      methods, is a formidable task. Here we present a strategy to overcome this
      problem combining multifrequency HYSCORE and ENDOR measurements on site
      specifically 13C-labeled samples with DFT calculations on model systems. As a
      demonstration of this approach, pulsed EPR experiments are performed on the
      primary QA and secondary QB ubisemiquinones of the photosynthetic reaction center
      from Rhodobacter sphaeroides 13C-labeled at the ring and tail positions. Despite
      the large number of nuclei interacting with the unpaired electron in these
      samples, two-dimensional X- and Q-band HYSCORE and orientation selective Q-band
      ENDOR resolve and allow for a characterization of the eight expected 13C
      resonances from significantly different hyperfine tensors for both semiquinones.
      From these results we construct, for the first time, the most complete
      experimentally determined maps of the s- and ppi-orbital spin density
      distributions for any protein organic cofactor radical to date. This work lays a
      foundation for understanding the relationship between the electronic structure of
      semiquinones and their functional properties, and introduces new techniques for
      mapping out the spin density distribution that are readily applicable to other
      systems.

PMID- 29035063
TI  - Religious anti-gay prejudice as a predictor of mental health, abuse, and
      substance use.
AB  - Anti-gay, or homonegative, prejudice is generally considered harmful to the
      wellbeing of sexual minority individuals. However, the origins or nature of such
      prejudice may vary. Despite a sizable body of literature suggesting homonegative
      prejudice is frequently religious-based, the psychological impact of exposure to
      religious anti-gay prejudice remains largely undetermined. Addressing this
      research gap, the authors examined whether opposition to same-sex sexuality on
      religious grounds predicted detrimental outcomes among same- and both-sex
      attracted individuals, as well as their heterosexual counterparts. A nationwide
      U.S. sample of 1600 individuals-recruited using contemporary online crowd
      sourcing techniques designed to limit selection bias-completed a novel inventory
      assessing interpersonal exposure to religious (as well as nonreligious)
      homonegative disapproval. Outcome variables assessed included a number of
      clinically relevant measures spanning general mental health, social support,
      suicidality, abuse, and substance use. Analyses revealed that greater exposure to
      religious anti-gay prejudice predicted higher levels of anxiety, stress, and
      shame; more instances of physical and verbal abuse; and more problematic alcohol
      use. Furthermore, while sexual minority individuals tended to fare more poorly
      than their heterosexual counterparts on almost every outcome measure assessed,
      homonegative prejudice predicted poorer outcomes among all respondents regardless
      of their sexual orientation or religious identification. Hence, results are among
      the first to demonstrate that anti-gay religious exposure is associated with
      substantial threats to wellbeing, and that such effects may be observed beyond
      religious sexual minorities. Overall, findings imply that homonegative religious
      social conditions may be of broader health and mental health concern than is
      conventionally recognized. (PsycINFO Database Record

PMID- 29035065
TI  - Serial decision-making in monkeys during an oculomotor task.
AB  - Much of everyday behavior involves serial decision-making, in which the outcome
      of 1 choice affects another. An example is setting rules for oneself: choosing a
      behavioral rule guides appropriate choices in the future. How the brain links
      decisions across time is poorly understood. Neural mechanisms could be studied in
      monkeys, as it is known that they can select and use behavioral rules, but
      existing psychophysical paradigms are poorly suited for the constraints of
      neurophysiology. Therefore, we designed a streamlined task that requires
      sequential, linked decisions, and trained 2 rhesus monkeys (Macaca mulatta) to
      perform it. The task features trial-by-trial consistency, visual stimuli, and eye
      movement responses to optimize it for simultaneous electrophysiological inquiry.
      In the first stage of each trial, the monkeys selected a rule or a rule was
      provided to them. In the second stage, they used the rule to discriminate between
      2 test stimuli. Our hypotheses were that they could use self-selected rules and
      could deliberately select rules based on reinforcement history. We found that the
      monkeys were as proficient at using self-selected rules as instructed rules.
      Their preferences for selecting rules correlated with their performance in using
      them, consistent with systematic, rather than random, strategies for
      accomplishing the task. The results confirm and extend prior findings on rule
      selection in monkeys and establish a viable, experimentally flexible paradigm for
      studying the neural basis of serial decision-making. (PsycINFO Database Record

PMID- 29035064
TI  - Two subtypes of psychopathic criminals differ in negative affect and history of
      childhood abuse.
AB  - OBJECTIVE: Specification of the etiological mechanisms underlying psychopathy is
      a key step in developing more effective methods for preventing and remediating
      the callous and impulsive behavior that characterizes the disorder. Theoretical
      conceptualizations of psychopathic subtypes propose that a primary variant
      largely stems from impoverished affect, whereas a secondary variant is
      hypothesized to develop subsequent to adverse environmental experiences (e.g.,
      childhood maltreatment). However, there has been a dearth of research
      demonstrating that psychopathic subtypes actually differ in terms of experienced
      childhood maltreatment in an adult offender population. METHOD: The current study
      employed model-based cluster analysis (MBCA) in a sample of incarcerated,
      psychopathic males (n = 110) to identify subtypes of psychopathic offenders based
      on a broad personality assessment. RESULTS: Two subgroups emerged: 1 with high
      levels of negative affect (high-NA) and 1 with low levels of negative affect (low
      NA). The high-NA subgroup scored significantly higher on measures of childhood
      maltreatment. CONCLUSION: These results provide support for theoretical
      conceptualizations of psychopathic subtypes, suggesting that psychopathic
      offenders with high levels of negative affect experience a greater degree of
      childhood maltreatment. (PsycINFO Database Record

PMID- 29035066
TI  - Multiple self-reported sleep measures are differentially associated with
      cognitive performance in community-dwelling nondemented elderly.
AB  - OBJECTIVE: To examine associations between daytime and insomnia-related sleep
      problems with different domains of cognitive functioning and determine whether
      subclinical depressive symptoms and age moderate these associations. METHOD: A
      total of 903 cognitively healthy older adults enrolled in a longitudinal aging
      study completed the UDS neuropsychological battery (measuring attention,
      executive functioning, episodic memory, language and processing speed).
      Subclinical depressive symptoms were also assessed and self-reported measures of
      sleep were administered. RESULTS: Hierarchical multiple regression analyses
      separately assessing the effects of daytime and insomnia-related sleep problems
      on cognition identified relationships between both daytime and insomnia-related
      sleep problems with a composite measure of executive functioning; however, the
      former was related more to speed of processing and the latter to higher order
      executive abilities. Age moderated the relationship between insomnia severity and
      executive functioning, and subclinical depressive symptoms moderated the
      relationship between insomnia-related sleep problems and performance on measures
      of attention. CONCLUSIONS: Among older adults, sleep problems have a deleterious
      effect on executive functioning regardless of whether they occur during the day
      or nighttime; however, age and subclinical depressive symptoms differentially
      impact relationships between sleep variables and cognitive domains. (PsycINFO
      Database Record

PMID- 29035067
TI  - Executive functioning in relation to coping in mild versus moderate-severe
      traumatic brain injury.
AB  - OBJECTIVE: To examine associations between executive functioning (EF) and coping
      styles, separately for mild and moderate-severe traumatic brain injury (TBI) in
      the chronic phase postinjury. METHOD: Patients with mild (n = 47) and moderate
      severe TBI (n = 59) were included, in addition to healthy controls (HCs; n = 51).
      Assessment consisted of EF tests (Trail Making Test, Zoo Map Test, Controlled
      Oral Word Association Test) and questionnaires examining EF (Dysexecutive
      Questionnaire) and coping styles (Utrecht Coping List). RESULTS: Moderate-severe
      TBI patients showed significant more EF deficits, lower active coping and higher
      passive coping than mild TBI patients and HCs, whereas mild TBI patients did not
      differ from HCs. In the moderate-severe TBI group, a higher number of self
      reported EF problems was related to lower levels of active coping, r = -.43, p <
      .01 and higher levels of passive coping, r = .58, p < .001, with proxy-reports
      relating to lower levels of active coping, r = -.33, p < .05. For mild TBI, a
      higher amount of self-reported EF problems was related to lower levels of active
      coping, r = -.38, p < .05 and higher levels of passive coping, r = .55, p < .001,
      with proxy-reports relating to higher levels of passive coping, r = .39, p < .05.
      Except for mental flexibility, EF performances were not associated with coping.
      CONCLUSIONS: This study shows strong associations between reported EF problems in
      daily life and coping styles. For moderate-severe TBI, proxy-reports may reflect
      EF impairments that complicate active problem-solving. However, reported EF
      problems by mild and moderate-severe TBI patients are also likely to reflect a
      psychological distress related to the way patients are inclined to deal with
      stressing situations that put a demand on their executive abilities. (PsycINFO
      Database Record

PMID- 29035068
TI  - Effects of animal-assisted therapy on concentration and attention span in
      patients with acquired brain injury: A randomized controlled trial.
AB  - OBJECTIVE: Previous studies have reported that brain-injured patients frequently
      suffer from cognitive impairments such as attention and concentration deficits.
      Numerous rehabilitation clinics offer animal-assisted therapy (AAT) to address
      these difficulties. The authors' aim was to investigate the immediate effects of
      AAT on the concentration and attention span of brain-injured patients. METHOD:
      Nineteen patients with acquired brain injury were included in a randomized,
      controlled, within-subject trial. The patients alternately received 12 standard
      therapy sessions (speech therapy, physiotherapy, occupational therapy) and 12
      paralleled AAT sessions with comparable content. A total of 429 therapy sessions
      was analyzed consisting of 214 AAT and 215 control sessions. Attention span and
      instances of distraction were assessed via video coding in Noldus Observer. The
      Mehrdimensionaler Befindlichkeitsbogen ([Multidimensional Affect Rating Scale]
      MDBF questionnaire; Steyer, Schwenkmezger, Notz, & Eid, 1997) was used to measure
      the patient's self-rated alertness. Concentration was assessed through Visual
      Analogue Scale (VAS) via self-assessment and therapist's ratings. RESULTS: The
      patients' attention span did not differ whether an animal was present or not.
      However, patients displayed more instances of distraction during AAT. Moreover,
      patients rated themselves more concentrated and alert during AAT sessions.
      Further, therapists' evaluation of patients' concentration indicated that
      patients were more concentrated in AAT compared with the control condition.
      CONCLUSIONS: Although the patients displayed more instances of distraction while
      in the presence of an animal, it did not have a negative impact on their
      attention span. In addition, patients reported to be more alert and concentrated
      when an animal was present. Future studies should examine other attentional
      processes such as divided attention and include neurobiological correlates of
      attention. (PsycINFO Database Record

PMID- 29035069
TI  - Emotion recognition in Parkinson's disease: Static and dynamic factors.
AB  - OBJECTIVE: The authors tested the hypothesis that Parkinson's disease (PD)
      participants would perform better in an emotion recognition task with dynamic
      (video) stimuli compared to a task using only static (photograph) stimuli and
      compared performances on both tasks to healthy control participants. METHOD: In a
      within-subjects study, 21 PD participants and 20 age-matched healthy controls
      performed both static and dynamic emotion recognition tasks. The authors used a 2
      way analysis of variance (controlling for individual participant variance) to
      determine the effect of group (PD, control) on emotion recognition performance in
      static and dynamic facial recognition tasks. RESULTS: Groups did not
      significantly differ in their performances on the static and dynamic tasks;
      however, the trend was suggestive that PD participants performed worse than
      controls. CONCLUSIONS: PD participants may have subtle emotion recognition
      deficits that are not ameliorated by the addition of contextual cues, similar to
      those found in everyday scenarios. Consistent with previous literature, the
      results suggest that PD participants may have underlying emotion recognition
      deficits, which may impact their social functioning. (PsycINFO Database Record

PMID- 29035070
TI  - Verbal fluency in male and female schizophrenia patients: Different patterns of
      association with processing speed, working memory span, and clinical symptoms.
AB  - OBJECTIVE: Decreased processing speed in schizophrenia patients has been
      identified as a major impairment factor in various neuropsychological domains.
      Working memory span has been found to be involved in several deep or effortful
      cognitive processes. We investigated the impact that these 2 cognitive functions
      may have on phonological and semantic fluency in schizophrenia patients and
      healthy participants. METHOD: Fifty-five patients with schizophrenia and 60
      healthy participants were administered a neuropsychological battery including
      phonological and semantic fluency, working memory, and cognitive and motor speed.
      RESULTS: Regression analyses revealed that motor speed was related to
      phonological fluency in female patients, whereas cognitive speed was related to
      semantic fluency in male patients. In addition, working memory span was related
      to verbal fluency in women from both the patient and the healthy control groups.
      Decreased processing speed, but not decreased working memory span, accounted for
      the verbal fluency deficit in patients. Verbal fluency was inversely related to
      attention deficit in female patients and to negative symptoms in male patients.
      CONCLUSIONS: Decreased processing speed may be the main factor in verbal fluency
      impairment of patients. Further, the cognitive and clinical predictors of verbal
      fluency efficiency are different in men and women. (PsycINFO Database Record

PMID- 29035071
TI  - Focused cognitive control in dishonesty: Evidence for predominantly transient
      conflict adaptation.
AB  - Giving a dishonest response to a question entails cognitive conflict due to an
      initial activation of the truthful response. Following conflict monitoring
      theory, dishonest responding could therefore elicit transient and sustained
      control adaptation processes to mitigate such conflict, and the current
      experiments take on the scope and specificity of such conflict adaptation in
      dishonesty. Transient adaptation reduces differences between honest and dishonest
      responding following a recent dishonest response. Sustained adaptation has a
      similar behavioral signature but is driven by the overall frequency of dishonest
      responding. Both types of adaptation to recent and frequent dishonest responses
      have been separately documented, leaving open whether control processes in
      dishonest responding can flexibly adapt to transient and sustained conflict
      signals of dishonest and other actions. This was the goal of the present
      experiments which studied (dis)honest responding to autobiographical yes/no
      questions. Experiment 1 showed robust transient adaptation to recent dishonest
      responses whereas sustained control adaptation failed to exert an influence on
      behavior. It further revealed that transient effects may create a spurious
      impression of sustained adaptation in typical experimental settings. Experiments
      2 and 3 examined whether dishonest responding can profit from transient and
      sustained adaption processes triggered by other behavioral conflicts. This was
      clearly not the case: Dishonest responding adapted markedly to recent (dis)honest
      responses but not to any context of other conflicts. These findings indicate that
      control adaptation in dishonest responding is strong but surprisingly focused and
      they point to a potential trade-off between transient and sustained adaptation.
      (PsycINFO Database Record

PMID- 29035073
TI  - Contextual cueing of tactile search is coded in an anatomical reference frame.
AB  - This work investigates the reference frame(s) underlying tactile context memory,
      a form of statistical learning in a tactile (finger) search task. In this task,
      if a searched-for target object is repeatedly encountered within a stable spatial
      arrangement of task-irrelevant distractors, detecting the target becomes more
      efficient over time (relative to nonrepeated arrangements), as learned target
      distractor spatial associations come to guide tactile search, thus cueing
      attention to the target location. Since tactile search displays can be
      represented in several reference frames, including multiple external and an
      anatomical frame, in Experiment 1 we asked whether repeated search displays are
      represented in tactile memory with reference to an environment-centered or
      anatomical reference frame. In Experiment 2, we went on examining a hand-centered
      versus anatomical reference frame of tactile context memory. Observers performed
      a tactile search task, divided into a learning and test session. At the
      transition between the two sessions, we introduced postural manipulations of the
      hands (crossed <-> uncrossed in Expt. 1; palm-up <-> palm-down in Expt. 2) to
      determine the reference frame of tactile contextual cueing. In both experiments,
      target-distractor associations acquired during learning transferred to the test
      session when the placement of the target and distractors was held constant in
      anatomical, but not external, coordinates. In the latter, RTs were even slower
      for repeated displays. We conclude that tactile contextual learning is coded in
      an anatomical reference frame. (PsycINFO Database Record

PMID- 29035072
TI  - Distinguishing among potential mechanisms of singleton suppression.
AB  - Previous research has revealed that people can suppress salient stimuli that
      might otherwise capture visual attention. The present study tests between 3
      possible mechanisms of visual suppression. According to first-order feature
      suppression models, items are suppressed on the basis of simple feature values.
      According to second-order feature suppression models, items are suppressed on the
      basis of local discontinuities within a given feature dimension. According to
      global-salience suppression models, items are suppressed on the basis of their
      dimension-independent salience levels. The current study distinguished among
      these models by varying the predictability of the singleton color value. If items
      are suppressed by virtue of salience alone, then it should not matter whether the
      singleton color is predictable. However, evidence from probe processing and eye
      movements indicated that suppression is possible only when the color values are
      predictable. Moreover, the ability to suppress salient items developed gradually
      as participants gained experience with the feature that defined the salient
      distractor. These results are consistent with first-order feature suppression
      models, and are inconsistent with the other models of suppression. In other
      words, people primarily suppress salient distractors on the basis of their simple
      features and not on the basis of salience per se. (PsycINFO Database Record

PMID- 29035074
TI  - Biased guessing in a complete-identification visual-working-memory task: Further
      evidence for mixed-state models.
AB  - Research is reported that provides evidence for a significant role of mixed
      states and guessing processes in tasks of visual working memory (VWM). Subjects
      engaged in a complete-identification VWM task. The stimulus set consisted of 16
      colors roughly equally spaced around a color circle. On each trial, a memory-set
      drawn from the colors was briefly presented, followed by a location probe.
      Subjects attempted to reproduce the color of the probed item by clicking on the
      appropriate response button of a discrete color wheel. The key manipulation was
      to vary payoffs for alternative correct responses across trials. Analysis of the
      resulting matrices of individual-subject identification-confusion data provided
      evidence for a systematic guessing process: On trials in which subjects had no
      memory for the probed stimulus, they guessed with high probability using the high
      payoff response. Formal modeling corroborated this interpretation. Mixed-state
      models that assumed that performance involved a combination of memory-based
      responding and biased guessing yielded accurate and easy-to-interpret accounts of
      the identification data; by comparison, variable-resources (VR) models without a
      guessing state struggled to account for the data, including versions with bias
      parameters for the high-payoff response. The authors argue that the work adds to
      recent converging sources of evidence that point to a significant role of
      discrete, mixed states in VWM. The authors also suggest directions for
      development of extended VR models with sophisticated knowledge-rich decision
      rules for the complete-identification task. (PsycINFO Database Record

PMID- 29035075
TI  - Whatever you do, don't look at the...: Evaluating guidance by an exclusionary
      attentional template.
AB  - People can use a target template consisting of one or more features to guide
      attention and gaze to matching objects in a search array. But can we also use
      feature information to guide attention away from known irrelevant items? Some
      studies found a benefit from foreknowledge of a distractor feature, whereas
      others found a cost. Importantly, previous work has largely relied on end-of
      trial manual responses; it is unclear how feature-guided avoidance might unfold
      as candidate objects are inspected. In the current experiments, participants were
      cued with a distractor feature to avoid, then performed a visual search task
      while eye movements were recorded. Participants initially fixated a to-be-avoided
      object more frequently than predicted by chance, but they also demonstrated
      avoidance of cue-matching objects later in the trial. When provided more time
      between cue stimulus and search array, participants continued to be initially
      captured by a cued-color item. Furthermore, avoidance of cue-matching objects
      later in the trial was not contingent on initial capture by a cue-matching
      object. These results suggest that the conflicting findings in previous negative
      cue experiments may be explained by a mixture of two independent processes:
      initial attentional capture by memory-matching items and later avoidance of known
      irrelevant items. (PsycINFO Database Record

PMID- 29035077
TI  - Task conflict and proactive control: A computational theory of the Stroop task.
AB  - The Stroop task is a central experimental paradigm used to probe cognitive
      control by measuring the ability of participants to selectively attend to task
      relevant information and inhibit automatic task-irrelevant responses. Research
      has revealed variability in both experimental manipulations and individual
      differences. Here, we focus on a particular source of Stroop variability, the
      reverse-facilitation (RF; faster responses to nonword neutral stimuli than to
      congruent stimuli), which has recently been suggested as a signature of task
      conflict. We first review the literature that shows RF variability in the Stroop
      task, both with regard to experimental manipulations and to individual
      differences. We suggest that task conflict variability can be understood as
      resulting from the degree of proactive control that subjects recruit in advance
      of the Stroop stimulus. When the proactive control is high, task conflict does
      not arise (or is resolved very quickly), resulting in regular Stroop
      facilitation. When proactive control is low, task conflict emerges, leading to a
      slow-down in congruent and incongruent (but not in neutral) trials and thus to
      Stroop RF. To support this suggestion, we present a computational model of the
      Stroop task, which includes the resolution of task conflict and its modulation by
      proactive control. Results show that our model (a) accounts for the variability
      in Stroop-RF reported in the experimental literature, and (b) solves a challenge
      to previous Stroop models-their ability to account for reaction time
      distributional properties. Finally, we discuss theoretical implications to Stroop
      measures and control deficits observed in some psychopathologies. (PsycINFO
      Database Record

PMID- 29035076
TI  - Internal and external sources of variability in perceptual decision-making.
AB  - It is important to identify sources of variability in processing to understand
      decision-making in perception and cognition. There is a distinction between
      internal and external variability in processing, and double-pass experiments have
      been used to estimate their relative contributions. In these and our experiments,
      exact perceptual stimuli are repeated later in testing, and agreement on the 2
      trials is examined to see if it is greater than chance. In recent research in
      modeling decision processes, some models implement only (internal) variability in
      the decision process whereas others explicitly represent multiple sources of
      variability. We describe 5 perceptual double-pass experiments that show greater
      than chance agreement, which is inconsistent with models that assume internal
      variability alone. Estimates of total trial-to-trial variability in the evidence
      accumulation (drift) rate (the decision-relevant stimulus information) were
      estimated from fits of the standard diffusion decision-making model to the data.
      The double-pass procedure provided estimates of how much of this total
      variability was systematic and dependent on the stimulus. These results provide
      the first behavioral evidence independent of model fits for trial-to-trial
      variability in drift rate in tasks used in examining perceptual decision-making.
      (PsycINFO Database Record

PMID- 29035079
TI  - Action and perception in literacy: A common-code for spelling and reading.
AB  - There is strong evidence that reading and spelling in alphabetical scripts depend
      on a shared representation (common-coding). However, computational models usually
      treat the two skills separately, producing a wide variety of proposals as to how
      the identity and position of letters is represented. This article treats reading
      and spelling in terms of the common-coding hypothesis for perception-action
      coupling. Empirical evidence for common representations in spelling-reading is
      reviewed. A novel version of the Start-End Competitive Queuing (SE-CQ) spelling
      model is introduced, and tested against the distribution of positional errors in
      Letter Position Dysgraphia, data from intralist intrusion errors in spelling to
      dictation, and dysgraphia because of nonperipheral neglect. It is argued that no
      other current model is equally capable of explaining this range of data. To
      pursue the common-coding hypothesis, the representation used in SE-CQ is applied,
      without modification, to the coding of letter identity and position for reading
      and lexical access, and a lexical matching rule for the representation is
      proposed (Start End Position Code model, SE-PC). Simulations show the model's
      compatibility with benchmark findings from form priming, its ability to account
      for positional effects in letter identification priming and the positional
      distribution of perseverative intrusion errors. The model supports the view that
      spelling and reading use a common orthographic description, providing a well
      defined account of the major features of this representation. (PsycINFO Database
      Record

PMID- 29035078
TI  - Overrepresentation of extreme events in decision making reflects rational use of
      cognitive resources.
AB  - People's decisions and judgments are disproportionately swayed by improbable but
      extreme eventualities, such as terrorism, that come to mind easily. This article
      explores whether such availability biases can be reconciled with rational
      information processing by taking into account the fact that decision makers value
      their time and have limited cognitive resources. Our analysis suggests that to
      make optimal use of their finite time decision makers should overrepresent the
      most important potential consequences relative to less important, put potentially
      more probable, outcomes. To evaluate this account, we derive and test a model we
      call utility-weighted sampling. Utility-weighted sampling estimates the expected
      utility of potential actions by simulating their outcomes. Critically, outcomes
      with more extreme utilities have a higher probability of being simulated. We
      demonstrate that this model can explain not only people's availability bias in
      judging the frequency of extreme events but also a wide range of cognitive biases
      in decisions from experience, decisions from description, and memory recall.
      (PsycINFO Database Record

PMID- 29035080
TI  - Neural scaling laws for an uncertain world.
AB  - Autonomous neural systems must efficiently process information in a wide range of
      novel environments which may have very different statistical properties. We
      consider the problem of how to optimally distribute receptors along a 1
      dimensional continuum consistent with the following design principles. First,
      neural representations of the world should obey a neural uncertainty principle
      making as few assumptions as possible about the statistical structure of the
      world. Second, neural representations should convey, as much as possible,
      equivalent information about environments with different statistics. The results
      of these arguments resemble the structure of the visual system and provide a
      natural explanation of the behavioral Weber-Fechner law, a foundational result in
      psychology. Because the derivation is extremely general, this suggests that
      similar scaling relationships should be observed not only in sensory continua,
      but also in neural representations of "cognitive" 1-dimensional quantities such
      as time or numerosity. (PsycINFO Database Record

PMID- 29035081
TI  - Biological evaluation of novel curcumin-pyrazole-mannich derivative active
      against drug-resistant Mycobacterium tuberculosis.
AB  - AIM: Our objective was to identify a more potent curcumin derivative with
      specific activity against Mycobacterium tuberculosis. MATERIALS & METHODS: A
      total of 21 curcumin derivatives were synthesized and detailed bio-evaluation was
      carried out including determination of static/cidality, synergy with front-line
      antituberculosis drugs and determination of efficacy in the murine model of M.
      tuberculosis infection. RESULTS: We identified CPMD-6d dihydrochloride exhibiting
      concentration-dependent bactericidal activity against M. tuberculosis (MIC 2
      MUg/ml), even against drug-resistant strains. In addition, it synergizes with
      front-line antituberculosis drugs as well as significantly reduces bacterial load
      in mice lungs and spleen at 25 mg/kg as compared with ethambutol at 100 mg/kg.
      CONCLUSION: Taken together, CPMD-6d dihydrochloride exhibits all properties to be
      positioned as a novel molecule of interest for treatment of tuberculosis.
      Graphical abstract: [Formula: see text].

PMID- 29035082
TI  - All for one or one for all? Authorship and the cross-sectoral valuation of credit
      in nutrition science.
AB  - The passionate pursuit of authorships is fuelled by the value they represent to
      scholars and scientists. This article asks how this value differs across
      scientists and how these different processes of valuation inform authorship
      articulation, strategies, and publication behavior in general. Drawing from a
      qualitative analysis of authorship practices among nutrition scientists employed
      at universities, contract research organizations, and in food industry, I argue
      that two different modi operandi emerge when it comes to authorship. These
      different ways of working produce different collaborative approaches, different
      credit distribution strategies amongst collaborators, and different value placed
      upon (the pursuit of) authorship. These different valuation processes are neither
      explicit nor recognizable to those reading (and judging) author lists. As a
      consequence, in the politics of authorship, the names standing atop a scientific
      publication in nutrition science represent different types of value to both the
      individuals and employing organizations.

PMID- 29035083
TI  - Multiplicity-adjusted semiparametric benefiting subgroup identification in
      clinical trials.
AB  - Background A recent focus in the health sciences has been the development of
      personalized medicine, which includes determining the population for which a
      given treatment is effective. Due to limited data, identifying the true
      benefiting population is a challenging task. To tackle this difficulty, the
      credible subgroups approach provides a pair of bounding subgroups for the true
      benefiting subgroup, constructed so that one is contained by the benefiting
      subgroup while the other contains the benefiting subgroup with high probability.
      However, the method has so far only been developed for parametric linear models.
      Methods In this article, we develop the details required to follow the credible
      subgroups approach in more realistic settings by considering nonlinear and
      semiparametric regression models, supported for regulatory science by conditional
      power simulations. We also present an improved multiple testing approach using a
      step-down procedure. We evaluate our approach via simulations and apply it to
      data from four trials of Alzheimer's disease treatments carried out by AbbVie.
      Results Semiparametric modeling yields credible subgroups that are more robust to
      violations of linear treatment effect assumptions, and careful choice of the
      population of interest as well as the step-down multiple testing procedure result
      in a higher rate of detection of benefiting types of patients. The approach
      allows us to identify types of patients that benefit from treatment in the
      Alzheimer's disease trials. Conclusion Attempts to identify benefiting subgroups
      of patients in clinical trials are often met with skepticism due to a lack of
      multiplicity control and unrealistically restrictive assumptions. Our proposed
      approach merges two techniques, credible subgroups, and semiparametric
      regression, which avoids these problems and makes benefiting subgroup
      identification practical and reliable.

PMID- 29035084
TI  - Traffic Injury Prevention.

PMID- 29035085
TI  - Lung Microbiota Is Related to Smoking Status and to Development of Acute
      Respiratory Distress Syndrome in Critically Ill Trauma Patients.
AB  - RATIONALE: Cigarette smoking is associated with increased risk of acute
      respiratory distress syndrome (ARDS) in patients after severe trauma; however,
      the mechanisms underlying this association are unknown. OBJECTIVES: To determine
      whether cigarette smoking contributes to ARDS development after trauma by
      altering community composition of the lung microbiota. METHODS: We studied the
      lung microbiota of mechanically ventilated patients admitted to the ICU after
      severe blunt trauma. To do so, we used 16S ribosomal RNA gene amplicon sequencing
      of endotracheal aspirate samples obtained on ICU admission (n = 74) and at 48
      hours after admission (n = 30). Cigarette smoke exposure (quantified using plasma
      cotinine), ARDS development, and other clinical parameters were correlated with
      lung microbiota composition. MEASUREMENTS AND MAIN RESULTS: Smoking status was
      significantly associated with lung bacterial community composition at ICU
      admission (P = 0.007 by permutational multivariate ANOVA [PERMANOVA]) and at 48
      hours (P = 0.03 by PERMANOVA), as well as with significant enrichment of
      potential pathogens, including Streptococcus, Fusobacterium, Prevotella,
      Haemophilus, and Treponema. ARDS development was associated with lung community
      composition at 48 hours (P = 0.04 by PERMANOVA) and was characterized by relative
      enrichment of Enterobacteriaceae and of specific taxa enriched at baseline in
      smokers, including Prevotella and Fusobacterium. CONCLUSIONS: After severe blunt
      trauma, a history of smoking is related to lung microbiota composition, both at
      the time of ICU admission and at 48 hours. ARDS development is also correlated
      with respiratory microbial community structure at 48 hours and with taxa that are
      relatively enriched in smokers at ICU admission. The data derived from this pilot
      study suggest that smoking-related changes in the lung microbiota could be
      related to ARDS development after severe trauma.

PMID- 29035086
TI  - NOTCH Signaling Is Essential for Maturation, Self-Renewal, and Tri
      Differentiation of In Vitro Derived Human Neural Stem Cells.
AB  - Although neural stem cells (NSCs) have potential applications in treating
      neurological disorders, much still needs to be understood about the
      differentiation biology for their successful clinical translation. In this study,
      we aimed at deriving NSCs from human umbilical cord blood-derived mesenchymal
      stem cells (hUCB-MSCs) and explored the role of Notch signaling in the
      differentiation process. The hUCB-MSCs were characterized as per guidelines of
      the International Society of Cellular Therapy. NSCs were successfully generated
      from hUCB-MSCs by using epidermal and fibroblast growth factors under serum-free
      conditions. The expression of NSC markers (Nestin and Musashi-1) in the
      neurospheres generated from hUCB-MSCs in the presence or absence of N-[N-(3,5
      difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT; Notch
      inhibitor) was immuno-phenotypically characterized by using immunofluorescence.
      DAPT showed significant (*p < 0.05) downregulated expression of the NSC markers
      Nestin and SOX2-at different time points (6 hours, 12 hours, 24 hours, 36 hours,
      and 5 days) post-treatment. In addition, Mushashi-1 (NSC marker) expression in
      NSCs was also inhibited after DAPT treatment, which signifies that the process is
      Notch dependent. These data were further correlated with formation of a reduced
      average number of neurospheres derived from hUCB-MSCs (2 colonies vs. 11
      colonies/field of view) in the presence of DAPT compared with the control
      (without DAPT). The expression of Notch target genes in NSC cultures (Notch
      intracellular domain [NICD], HES1, and HES5) was also significantly downregulated
      after DAPT treatment. In the presence of DAPT, the markers for neuronal (MAP2,
      NEFH); and glial (GFAP, GLUL, and MBP) lineages were significantly downregulated
      as seen via immunofluorescence and quantitative polymerase chain reaction,
      indicating the role of Notch in the tri-differentiation mechanism of NSCs as
      well. In addition, Notch signaling inhibition induced higher cell death during
      the lineage commitment of NSCs as measured 3 days (16.9% vs. 8.9%) and 6 days
      (42.9% vs. 20.8%) postinduction. These results suggest that the efficient
      derivation of NSCs and their subsequent lineage commitment from hUCB-MSCs
      requires the Notch signaling pathway.

PMID- 29035088
TI  - The Last 25 Years of Obstructive Sleep Apnea Epidemiology-and the Next 25?

PMID- 29035087
TI  - Xeroderma pigmentosum complementation group D polymorphism toward lung cancer
      susceptibility survival and response in patients treated with platinum
      chemotherapy.
AB  - AIM: The study investigated role of xeroderma pigmentosum complementation group D
      (XPD) single nucleotide polymorphisms in modulating lung cancer risk and its
      association with overall survival and clinical outcomes. METHODS:  XPD
      polymorphisms were detected using polymerase chain reaction restriction fragment
      length polymorphism (PCR-RFLP). RESULTS:  CC genotype of A751C polymorphism was
      associated with an increased lung cancer risk (p = 0.01). Classification and
      Regression Tree (CART) analysis depicted C156A as the major contributing factor.
      Patients having CC, treated with irinotecan-cisplatin/carboplatin regimen showed
      a better survival (median survival time = 25.2) whereas a poor survival was for
      XPD G312A. Similarly, patients treated with pemetrexed and carrying heterozygous
      genotype of G312A polymorphism had a poor survival (p = 0.01). CONCLUSION:  A751C
      and G312A act as a predictive marker in lung cancer patients treated with
      platinum chemotherapy. These findings might facilitate therapeutic decisions for
      individualized therapy in lung cancer patient. [Formula: see text].

PMID- 29035091
TI  - Inverse Relationship between Soluble RAGE and Risk for Bronchopulmonary
      Dysplasia.

PMID- 29035089
TI  - Intent to quit, quit attempts, and perceived health risk reduction among African
      American, Latino, and White nondaily and daily smokers in the United States.
AB  - OBJECTIVE: Ethnic and racial differences in smoking patterns and behaviors have
      been well documented and most African American and Latino smokers are nondaily or
      light smokers. However, differences within smoking levels are understudied. Our
      primary aim was to determine whether there are racial and ethnic differences
      among African American, Latino, and White nondaily, light daily, and moderate to
      heavy daily smokers on (1) perceived health risk reduction, (2) intentions to
      quit, and (3) past year quit attempts. DESIGN: Smokers were recruited through an
      online research panel for a cross-sectional survey (n = 2376). Sampling quotas
      were used to obtain equal numbers of African American, Latino, and White nondaily
      and daily smokers. RESULTS: African American (59.6%) and Latino (54%) nondaily
      smokers were more likely than White nondaily smokers (45%) to currently limit
      their cigarettes per day (cpd) as a perceived health risk reduction strategy (p <
      0.05). African American nondaily smokers were more likely than Latino and White
      nondaily smokers (p < 0.05) to limit their smoking in the past year as a
      perceived health risk reduction strategy (range: 0 'never' to 5 'always'; Means =
      3.2, 2.9, 3.0, standard deviations [SD] = 1.1, 1.1, 1.2, respectively). African
      American nondaily smokers (15%) were more likely than either Latinos (7.8%) or
      Whites (8.5%) to intend to quit in the next 30 days (p < 0.01). African American
      (61.6%) and Latino (60.3%) nondaily smokers were more likely than Whites (49%) to
      have made a quit attempt in the past year (p < 0.01). Fewer racial and ethnic
      differences were found among daily smokers. CONCLUSIONS: Racial and ethnic group
      differences were more pronounced among nondaily smokers compared to light daily
      smoker and moderate to heavy daily smokers. Smoking level is an important
      consideration in understanding racial and ethnic variation in perceived health
      risk reduction and cessation-related behaviors.

PMID- 29035092
TI  - Vitamin D supplementation and non-alcoholic fatty liver disease: A critical and
      systematic review of clinical trials.
AB  - Previous observational studies have found a relationship between vitamin D
      deficiency and non-alcoholic fatty liver disease (NAFLD). However, this type of
      study could not show the causal relationship between these two conditions.
      Therefore, we systematically and critically reviewed the available clinical
      trials to elucidate such relationship. We searched databases such as Medline,
      Scopus and Cochrane to identify the clinical trials that assessed the effects of
      vitamin D supplementation in adults with NAFLD. The outcome variables of interest
      were indicators of hepatic steatosis, liver enzymes, insulin resistance,
      inflammation and oxidative stress. A total of 6 studies were included in the
      qualitative analysis. Only in two studies the grade of hepatic steatosis
      decreased significantly after vitamin D supplementation. The changes in insulin
      resistance parameters were reported significant only in one. Of the 3 included
      studies that measured biomarkers of inflammation and oxidative stress, one
      revealed a significant decrease in these biomarkers after vitamin D
      supplementation. Findings from current review study provided new insight into the
      factors that could affect the therapeutic role of vitamin D in NAFLD. Factors
      such as gender differences, baseline serum status of vitamin D, co
      supplementation with calcium and gene polymorphism should be considered when
      designing future clinical trials.

PMID- 29035090
TI  - Early Respiratory Bacterial Detection and Antistaphylococcal Antibiotic
      Prophylaxis in Young Children with Cystic Fibrosis.
AB  - RATIONALE: Consensus is lacking regarding antistaphylococcal antibiotic
      prophylaxis use for young children with cystic fibrosis. Prophylaxis is
      recommended in the United Kingdom, but it is recommended against in the United
      States. OBJECTIVES: To test the hypothesis that antistaphylococcal antibiotic
      prophylaxis is associated with a decreased risk of Staphylococcus aureus
      acquisition but no increased risk of Pseudomonas aeruginosa acquisition. METHODS:
      We undertook a longitudinal observational study of children with cystic fibrosis
      who were recruited from birth (or from their first registry entry in the period)
      and followed until the age of 4 years (1,500 d) using 2000-2009 data from the UK
      Cystic Fibrosis Trust and Cystic Fibrosis Foundation registries. Children were
      excluded if they had a positive culture result for S. aureus or P. aeruginosa, or
      if they were receiving inhaled antibiotics, at the first encounter. Time to first
      S. aureus and P. aeruginosa detection in the UK/U.S. cohorts was compared using a
      Cox proportional hazards model. A UK-based analysis compared the same for those
      receiving flucloxacillin with those who received no prophylaxis. We included the
      following covariates: sex, age at registry entry, dornase alfa use, genotype, and
      center size. RESULTS: The primary analysis comprised 1,074 UK and 3,677 U.S.
      children. The risk of first detection was greater in U.S. children than in UK
      children for S. aureus (hazard ratio [HR], 5.79; 95% confidence interval [CI],
      4.85, 6.90; P < 0.001) and P. aeruginosa (HR, 1.92; 95% CI, 1.65, 2.24; P <
      0.001). In the UK analysis, we compared 278 children receiving flucloxacillin and
      306 receiving no prophylaxis. Flucloxacillin was not associated with a reduced
      risk of S. aureus detection (HR, 1.22; 95% CI, 0.74, 2.0; P = 0.43), but it was
      associated with an increased risk of P. aeruginosa detection (HR, 2.53; 95% CI,
      1.71, 3.74; P < 0.001). None of the covariates significantly affected the risk
      estimate in either analysis. CONCLUSIONS: The risk of first detection of S.
      aureus and P. aeruginosa was greater in the United States than in the United
      Kingdom. In the United Kingdom, the risk of first P. aeruginosa detection was
      increased among those receiving flucloxacillin compared with those who received
      no prophylaxis. These observational findings should be examined in randomized
      controlled trials.

PMID- 29035093
TI  - Gastric Banding Surgery versus Continuous Positive Airway Pressure for
      Obstructive Sleep Apnea: A Randomized Controlled Trial.

PMID- 29035094
TI  - Doktor Kot, Doktor Sla - book doctors, plant doctors and the segmentation of the
      medical market place in Meghalaya, northeast India.
AB  - Despite decades of research on India's plural health care market, the practices
      of many local health traditions outside the allopathic and codified traditions
      are under-studied. Drawing on interview and observational data, this paper
      explores the space in which indigenous traditional Khasi healers in Meghalaya
      state, northeast India, practice. Khasi indigenous healers describe themselves as
      doktor sla, plant doctors, to distinguish themselves from doktor kot, or book
      doctors. This distinction operates as a rhetorical resource, utilised to carve a
      distinct sphere of expertise in relation to the allopathic sector, and to mark
      claims for the specifically local appropriateness of traditional practices within
      a shifting market of state-sponsored provision. Khasi healers are a heterogeneous
      group who treat a wide variety of conditions, including physical ailments which
      have no obvious correlates in biomedical systems, and musculoskeletal disorders,
      with which they have recognised expertise. In addition to claiming these discrete
      strengths, healers also present themselves as accommodating deficiencies in
      biomedicine, including inherent generic weaknesses of allopathic care as well as
      specific local gaps in rural health care provision. Thus, the expertise niches of
      traditional healers have evolved through their interactions with, and the needs
      of, the community, but also through managing a shifting boundary with biomedical
      practitioners, who are explicitly sceptical of their efficacy, but tacitly
      accepting of the ways in which they manage the gaps in biomedical provision.
      While codified non-biomedical traditions in India have engaged in universalising
      professionalising projects, in this setting at least, non-codified practitioners
      have instead utilised discourses of localism.

PMID- 29035095
TI  - A Prospective Validation of a Clinical Algorithm to Detect Tuberculosis in Child
      Contacts.

PMID- 29035097
TI  - Blood Eosinophilia Neither Reflects Tissue Eosinophils nor Worsens Clinical
      Outcomes in Chronic Obstructive Pulmonary Disease.

PMID- 29035098
TI  - Quality of life and subjective health status according to handgrip strength in
      the elderly: a cross-sectional study.
AB  - OBJECTIVES: The purpose of this cross-sectional study was to examine potential
      associations between handgrip strength and health-related quality of life, or
      subjective health status, in the elderly. METHOD: We performed secondary data
      analysis on 2377 elderly individuals aged >65 years. Raw data from the Korea
      National Health and Nutrition Examination Survey VI (2014-2015), were drawn from
      a representative national sample. RESULTS: Of those aged >=65 years or older,
      25.4% had low handgrip strength. After adjusting for confounding variables, the
      odds ratios of elderly individuals with low handgrip strength were 1.30 (95%
      confidence interval [CI]: 1.00-1.69) for mobility, 2.18 (95% CI: 1.47-3.22) for
      self-care, 1.70 (95% CI: 1.30-2.23) for usual activities, 1.30 (95% CI: 1.01
      1.67) for pain/discomfort, 1.03 (95% CI: 0.74-1.44) for anxiety/depression, 1.44
      (95% CI: 1.10-1.87) for the EQ-5D index, and 1.37 (95% CI: 1.08-1.73) for
      subjective health status. CONCLUSION: Health-related quality of life and
      subjective health status differ according to handgrip strength. Therefore,
      handgrip strength should be addressed to improve quality of life in elderly
      individuals. Elderly individuals require exercise education and adequate
      nutritional intake to increase handgrip strength.

PMID- 29035100
TI  - Serum lipid level and lifestyles are associated with carotid femoral pulse wave
      velocity among adults: 4.4-year prospectively longitudinal follow-up of a
      clinical trial.
AB  - Lifestyle modifications are recommended as the initial treatment for high blood
      pressure. The influence of dyslipidemia might be via moderate arterial stiffness,
      which results in hypertension and cardiovascular disease. We used data from a
      subgroup of the lifestyle, level of serum lipids/carotid femoral-pulse wave
      velocity (CF-PWV) Susceptibility BEST Study, a population-based study of
      community-dwelling adults aged 45-75 years. The serum lipid level and CF-PWV were
      measured at baseline, and lifestyle such as smoking status, sleeping habits, and
      the level of oil or salt intake was determined with the use of a validated
      questionnaire during follow-up. Arterial stiffness was determined as CF-PWV using
      an electrocardiogram after a mean follow-up of 4.4 years. Regression coefficients
      (95% CIs), adjusted for demographics, risk factors, cholesterol, and
      triglycerides (TGs), were calculated by linear regression. Logistic regression
      analysis was used to identify the association between the variables with CF-PWV
      independently. In the results, glucose and total cholesterol (TC) were associated
      with higher CF-PWV (p = 0.000) and lower-destiny lipoprotein was associated with
      lower CF-PWV (p = 0.001) after adjustments for age, sex, mean arterial pressure,
      and heart rate. There were significant associations observed for current salt
      intake in relation to CF-PWV (p-trend = 0.038) without adjustment. This
      association was retained after adjustments for covariates and had statistical
      significance (p-trend = 0.048) in model 3, which adjusted age, sex, baseline CF
      PWV, mean arterial pressure, heart rate waist circumference, education, smoking
      status, physical activity, diabetes mellitus (DM), heart disease, high-density
      lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, TGs,
      antihypertensive medicine, nitrate medicine, and antiplatelet medicine. Linear
      regression showed statistically significant associations between LDL and CF-PWV
      in the fully adjusted models (model 1 p = 0.010, model 2 p = 0.020, model 3 p =
      0.017). Logistic regression analysis showed that CF-PWV was independently
      associated with age (p = 0.000), TC (p = 0.000), TGs (p = 0.000), and homo
      cysteine (p = 0.000), and their odds ratios were 0.781, 3.424, 0.075, and 1.046,
      respectively. Our results showed a positive association between LDL and arterial
      stiffness, and suggested that less smoking status, sleeping disorder, and salt
      intake were associated with less arterial stiffness.

PMID- 29035099
TI  - Association between growth differentiation factor 15 and left ventricular
      hypertrophy in hypertensive patients and healthy adults.
AB  - Growth differentiation factor 15 (GDF-15) as an independent biomarker of
      cardiovascular diseases merits further evaluation. We studied the association
      between plasma GDF-15 levels and left ventricular hypertrophy (LVH) in
      hypertensive patients and healthy adults. Hypertensive LVH measurements were
      performed via echocardiography and analyzed using the cube formula, and human GDF
      15 together with interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9)
      concentrations were determined via enzyme-linked immunosorbent assay (ELISA). All
      data were analyzed using SPSS 13.0 software. A total of 302 participants were
      recruited for this clinical study. Circulating GDF-15, IL-6 and MMP-9 levels were
      significantly higher in LVH patients (n = 67) than in non-LVH patients (n = 172)
      and healthy controls (n = 63) (p < 0.001). After adjustment for confounders via
      multivariate logistic regression, elevated plasma GDF-15 concentrations remained
      independently associated with LVH in hypertensive patients. In addition, GDF-15
      was positively correlated with IL-6 and MMP-9 levels in human plasma,
      respectively, suggesting that a link exists between GDF-15 expression and
      inflammation. We also calculated an optimal GDF-15 cut-off point with which LVH
      severity can be predicted in the current study. In conclusion, GDF-15 is
      associated with hypertensive LVH and may be a powerful biomarker with which LVH
      risk can be predicted in patients with hypertension.

PMID- 29035101
TI  - Biofilm Formation, Antimicrobial Resistance, and Sanitizer Tolerance of
      Salmonella enterica Strains Isolated from Beef Trim.
AB  - In the beef industry, product contamination by Salmonella enterica is a serious
      public health concern, which may result in human infection and cause significant
      financial loss due to product recalls. Currently, the precise mechanism and
      pathogen source responsible for Salmonella contamination in commercial
      establishments are not well understood. We characterized 89 S. enterica strains
      isolated from beef trim with respect to their biofilm-forming ability,
      antimicrobial resistance, and biofilm cell survival/recovery growth after
      sanitizer exposure. A total of 28 Salmonella serovars was identified within these
      strains. The most common serovars identified were Anatum, Dublin, Montevideo, and
      Typhimurium, with these accounting for nearly half of the total strains. The vast
      majority (86%) of the strains was able to develop strong biofilms, and the
      biofilm-forming ability was highly strain dependent and related to cell surface
      expression of extracellular polymeric structures. These strains also demonstrated
      strong tolerance to quaternary ammonium chloride (QAC) and chlorine dioxide
      (ClO2), but were more sensitive to chlorine treatment. Sanitizer tolerance and
      bacterial postsanitization recovery growth were closely associated with strains'
      biofilm-forming ability. Thirty percent of the examined strains were found
      resistant to multiple antimicrobial agents and the resistance phenotypes were
      serovar associated, but not related to strains' biofilm-forming ability. Pulsed
      field gel electrophoresis analysis tended to group strains by serovar rather than
      by biofilm-forming ability. Collectively, these data indicate that the strong
      biofilm formers of certain S. enterica strains/serovars possess significant
      potential for causing meat product contamination in meat processing environment.

PMID- 29035102
TI  - Clinical News.

PMID- 29035103
TI  - Racial Disparities in the Association between Alcohol Use Disorders and Health in
      Black and White Women.
AB  - Adverse health attributed to alcohol use disorders (AUD) is more pronounced among
      black than white women. We investigated whether socioeconomic status (education
      and income), health care factors (insurance, alcoholism treatment), or
      psychosocial stressors (stressful life events, racial discrimination, alcoholism
      stigma) could account for black-white differences in the association between AUD
      and physical and functional health among current women drinkers 25 years and
      older (N = 8,877) in the National Epidemiological Survey on Alcohol and Related
      Conditions. Generalized linear regression tested how race interacted with the
      association between 12-month DSM-IV AUD in Wave 1 (2001-2002) and health in Wave
      2 (2004-2005), adjusted for covariates (age group, alcohol consumption, smoking,
      body mass index, physical activity, diabetes, cardiovascular disease, and
      arthritis). Black women with AUD had poorer health than white women with AUD
      (beta = -3.18, SE = 1.28, p < .05). This association was partially attenuated
      after adjusting for socioeconomic status, health care, and psychosocial factors
      (beta = -2.64, SE = 1.27, p < .05). In race-specific analyses, AUD was associated
      with poorer health for black but not white women. Accounting for black-white
      differences in AUD and physical and functional health among women requires
      investigation beyond traditional explanatory mechanisms.

PMID- 29035104
TI  - Association between discrimination and obesity in African-American men.
AB  - The objective of this study was to examine the association between discrimination
      and obesity among a U.S. nationally representative sample of African-American
      men. Data from the 2001-2003 National Survey of American Life (NSAL) were used to
      collect measures of everyday and major discrimination, and body mass index (BMI)
      taken from self-reports. Poisson regression with robust standard errors was
      applied to estimate the prevalence ratios of everyday and major discrimination as
      it relates to obesity (BMI >= 30 kg/m2), controlling for potential confounders.
      In the model that included both everyday and major discrimination, men who
      experienced any major discrimination had a higher likelihood of obesity
      (prevalence ratio [PR] = 1.33, 95% confidence interval [CI], 1.06, 1.66) than
      those who did not experience any major discrimination, controlling for age,
      marital status, income, education, major stressors, two or more chronic
      conditions, and physical activity. Exposure to any major discrimination was found
      to be associated with obesity in African-American men. Future studies among this
      population are needed to examine whether the observed changes in self-reports of
      major discrimination are associated with obesity, measured by BMI, over time. The
      health of African-American men must be a priority in reducing excess disparities
      in disease, disability, and death.

PMID- 29035106
TI  - Does the Hispanic health advantage extend to better management of hypertension?
      The role of socioeconomic status, sociobehavioral factors, and health care
      access.
AB  - Hispanics in the United States (and foreign-born Hispanics in particular) have
      relatively favorable health given their lower socioeconomic status compared to,
      for example, non-Hispanic whites. This phenomenon is often called the Hispanic
      health paradox (HHP). This study examines whether the previously documented HHP
      in hypertension prevalence extends to its management using clinical and self
      reported measures from the 2007-2012 National Health and Nutrition Examination
      Surveys. Multivariate models adjusting for demographic, socioeconomic, and
      sociobehavioral characteristics show an advantage among foreign-born Mexicans in
      hypertension prevalence relative to non-Hispanic whites (adjusted OR = 0.85).
      However, compared to non-Hispanic whites, foreign-born Mexicans were 38% less
      likely to receive treatment recommendations and, when advised to undergo
      treatment, were 60% less likely to adhere to treatment. Adjusting for health care
      access and utilization dramatically reduces disparities in hypertension control
      between foreign-born Mexicans and non-Hispanic whites, suggesting that
      insufficient systematic access to and use of quality health care erodes the HHP
      and contributes to the deterioration of health throughout the immigrant
      experience. Without appropriate interventions, particularly in health care access
      and utilization, poorer hypertension management among foreign-born Mexicans may
      negatively affect the Hispanic health profile, increase risk of cardiovascular
      disease-related mortality, and erode the Hispanic health advantage in the future.

PMID- 29035105
TI  - Racial/Ethnic Differences in Early-Life Mortality in the United States.
AB  - U.S. early-life (ages 1-24) deaths are tragic, far too common, and largely
      preventable. Yet demographers have focused scant attention on U.S. early-life
      mortality patterns, particularly as they vary across racial and ethnic groups. We
      employed the restricted-use 1999-2011 National Health Interview Survey-Linked
      Mortality Files and hazard models to examine racial/ethnic differences in early
      life mortality. Our results reveal that these disparities are large, strongly
      related to differences in parental socioeconomic status, and expressed through
      different causes of death. Compared to non-Hispanic whites, non-Hispanic blacks
      experience 60 percent and Mexican Americans 32 percent higher risk of death over
      the follow-up period, with demographic controls. Our finding that Mexican
      Americans experience higher early-life mortality risk than non-Hispanic whites
      differs from much of the literature on adult mortality. We also show that these
      racial/ethnic differences attenuate with controls for family structure and
      especially with measures of socioeconomic status. For example, higher mortality
      risk among Mexican Americans than among non-Hispanic whites is no longer
      significant once we controlled for mother's education or family income. Our
      results strongly suggest that eliminating socioeconomic gaps across groups is the
      key to enhanced survival for children and adolescents in racial/ethnic minority
      groups.

PMID- 29035107
TI  - Maternal Social Disadvantage and Newborn Telomere Length in Archived Dried Blood
      Spots from the Michigan Neonatal Biobank.
AB  - Telomeres are the protective caps at the ends of eukaryotic chromosomes. Short
      telomere length is associated with morbidity and mortality among adults and may
      mark the biological impact of social experiences. Using archived dried blood
      spots from the Michigan Neonatal Biobank, this study examined markers of maternal
      social disadvantage (educational attainment, receipt of public assistance,
      marital status, and race/ethnicity) from linked birth certificates as predictors
      of telomere length at birth in a sample of 192 singleton neonates born to non
      Hispanic black, non-Hispanic white, and Latina mothers aged 20-35 years.
      Consistent with two recent studies in newborns, but counter to the idea that
      maternal social disadvantage is associated with shorter offspring telomere
      length, we found that infants born to black mothers had longer telomeres than
      those born to white mothers (b = 0.12, SE = 0.06, p = .05). However, black/white
      differences in newborn telomere length varied by receipt of public assistance.
      Among newborns whose mothers received WIC and/or Medicaid, there were no
      significant black/white differences in telomere length (b = 0.09, SE = 0.08, p =
      .25). In contrast, among those whose mothers did not receive public assistance
      just 6 out of 69 infants born to black mothers versus 41 out of 69 infants born
      to white mothers-we found that babies born to black mothers had longer telomere
      length than babies born to white mothers (b = 0.37, SE = 0.16, p = .03). The
      interaction between black race/ethnicity and receipt of public assistance did not
      reach the conventional threshold for statistical significance (b = -0.22, SE =
      0.15, p = .13), suggesting that this finding may be due to chance. No other
      markers of maternal social disadvantage were related to infant telomere length.
      Although replication of these results in a larger sample with more infants born
      to black mothers with relatively high socioeconomic status is needed, this study
      offers preliminary support for the hypothesis that race/ethnic differences in
      newborn telomere length depend on social context.

PMID- 29035109
TI  - Disfluent whole-word repetitions in cluttering: Durational patterns and
      functions.
AB  - In this article, disfluent word-repetitions are analysed in cluttered and control
      speech. The main questions are the following: (1) Do different functions of word
      repetitions occur in different ratio in cluttered and control speech? (2) Are
      there any differences between PWC and control speakers in durational parameters
      of disfluent word-repetitions? Results show that there are differences between
      the two groups of speakers in the types of word-repetitions, and in their
      durational parameters. In cluttered speech, the most frequent type of repetitions
      were covert self-repairs while in control speech canonical repetitions are
      dominated. There were significant differences in the durational parameters of
      word-repetitions of both groups except in the function of covert self-monitoring.
      According to the results, it can be concluded that as in earlier studies,
      analysis of the frequency of types of disfluencies in themselves is not enough as
      this analysis does not always show the differences between the two groups. It is
      important to learn more about the durational and functional characteristics of
      the specific types of disfluencies comparing them in cluttered and control
      speech.

PMID- 29035108
TI  - The Contribution of Weight Status to Black-White Differences in Mortality.
AB  - This article examines the contribution of weight status to black-white (B-W)
      differences in mortality at ages 40-79 using data from the National Health and
      Nutrition Examination Survey. We measured body mass index (BMI) based on the
      highest BMI attained and contrasted the contribution of BMI to that of smoking
      and educational attainment. We estimated both additive and multiplicative models.
      In addition to estimating regression coefficients we asked what would happen to B
      W differences in mortality if blacks had the BMI distribution of whites, the
      smoking prevalence of whites, or the educational distribution of whites. B-W
      differences in BMI account for close to 30 percent of the B-W difference in
      female mortality but only about 1 percent of the B-W difference in male mortality
      at ages 40-79. In contrast, smoking makes a much larger contribution to the B-W
      difference in male (17 percent) than female (6 percent) mortality. Differences in
      educational attainment in turn explain 19 to 25 percent of the B-W mortality
      difference among men and women, respectively. Our results underscore the
      importance of two key risk factors as well as educational attainment in
      generating B-W differences in mortality.

PMID- 29035110
TI  - Early communicative skills of children with Klinefelter syndrome.
AB  - Many studies reported the presence of language impairments in children and
      adolescents with Klinefelter syndrome (KS). However, the first stage of their
      language development has been scarcely studied. The present study aimed to
      describe the spontaneous communicative production of 18-month-old children with
      KS, in comparison with that of typically developing (TD) male peers, aiming to
      verify the existence of different early communicative skills in both vocal and
      gestural modality and to identify the presence of possible associations with
      their later vocabulary size. Children with KS showed a lower competence in both
      lexical skills and emergent syntactic abilities than TD peers. No significant
      differences were found in gesture production. Considering the possibility of
      identifying an association between early communicative skills and later
      vocabulary size, the vocal production of TD children appeared to be significantly
      related to their later lexical skills; whereas, the number of gestures produced
      by children with KS appeared to be related to their later lexical abilities. The
      early detection of language risk factors will allow early intervention and
      careful monitoring of these children's communicative development.

PMID- 29035112
TI  - Celebrating 25 Years of the European Society of Gene and Cell Therapy.

PMID- 29035111
TI  - Identification of atopic dermatitis phenotypes with good responses to probiotics
      (Lactobacillus plantarum CJLP133) in children.
AB  - The therapeutic effect of probiotics in atopic dermatitis (AD) remains
      controversial and varies according to the individual patient. We aimed to
      identify a population of AD patients with a good clinical response to probiotic
      treatment. We recruited 76 children with a median age of 7.1 years who suffered
      from moderate to severe AD. After a 2-week washout period, all patients were
      given Lactobacillus plantarum CJLP133 at a dosage of 1*1010 colony-forming units
      once a day for 12 weeks. We measured eosinophil counts in the peripheral blood,
      the proportion of CD4+CD25+Foxp3+ regulatory T (Treg) cells in CD4+ T cells,
      serum total immunoglobulin E (IgE) levels, and specific IgE against common
      allergens before the start of the treatment (T1) and at discontinuation (T2).
      Responders were defined as patients with at least a 30% reduction in the SCORing
      of AD (SCORAD) index after treatment. There were 36 responders and 40 non
      responders after probiotic treatment. The median SCORAD was reduced from 29.5
      (range 20.6-46.3) at T1 to 16.4 (range 6.3-30.8) at T2 in the responder group
      (P<0.001). In multivariable logistic regression analysis, a good clinical
      response was significantly associated with high total IgE levels (aOR 5.1, 95% CI
      1.1-23.6), increased expression of transforming growth factor (TGF)-beta (aOR
      4.6, 95% CI 1.3-15.9), and a high proportion of Treg cells in CD4+ T cells (aOR
      3.7, 95% CI 1.1-12.7) at T1. In the responder group, the proportion of Treg cells
      was significantly increased after 12 weeks of treatment (P=0.004), while TGF-beta
      mRNA expression was decreased (P=0.017). Our results suggest that a subgroup of
      patients with a specific AD phenotype showing an immunologically active state
      (high total IgE, increased expression of TGF-beta, high numbers of Treg cells)
      may benefit from probiotic treatment with L. plantarum CJLP133.

PMID- 29035113
TI  - European Society of Gene and Cell Therapy (ESGCT) at 25: A Gene Therapy Community
      at Its Prime and on the Move.

PMID- 29035114
TI  - Gene Therapy: From Birth to Maturity Requires Commitment to Science and Ethics.

PMID- 29035115
TI  - Twenty-Five Years of Gene Therapy: Prof. George Dickson on Past Progress and
      Future Promise.

PMID- 29035116
TI  - A Personal Reflection from London.

PMID- 29035117
TI  - A Sophism in Vectorology: Turning Harmful Defective Retroviral Vectors into
      Helpful Replication-Competent Retroviruses Against Cancer.

PMID- 29035118
TI  - Clinical Gene Therapy for Neurodegenerative Diseases: Past, Present, and Future.
AB  - Clinical gene therapy has made important advances over the last decade. Among
      neurological diseases, severe genetic neurodegenerative conditions have been the
      focus of initial clinical applications. Gene therapy has also addressed complex
      neurodegenerative diseases, particularly Parkinson's disease, with encouraging
      results in human patients, demonstrating that specific targeting of central
      nervous system (CNS) cells is a relevant strategy for severe pathologies and that
      efficient access to the CNS with viral vectors is an achievable goal. The purpose
      of this review is to summarize the gene therapy clinical applications that have
      been conducted for neurodegenerative diseases. Limitations and hurdles to obtain
      and demonstrate benefit in patients, and the new developments that should allow
      new clinical applications with high beneficial potential are discussed.

PMID- 29035119
TI  - Response to letter to the editor from Elinder and Nordberg concerning Byber et
      al. 2016. Cadmium or cadmium compounds and chronic kidney disease in workers and
      the general population: a systematic review, Crit Rev Toxicol. 46(3):191-240.
      DOI: 0.3109/10408444.2015.1076375.

PMID- 29035120
TI  - Use of a Remote Inhaler Monitoring Device to Measure Change in Inhaler Use with
      Chronic Obstructive Pulmonary Disease Exacerbations.
AB  - BACKGROUND: Remote inhaler monitoring is an emerging technology that enables the
      healthcare team to monitor the time and location of a patient's inhaler use. We
      assessed the feasibility of remote inhaler monitoring for chronic obstructive
      pulmonary disease (COPD) patients and the pattern of albuterol inhaler use
      associated with COPD exacerbations. METHODS: Thirty-five participants with COPD
      used an electronic inhaler sensor for 12 weeks which recorded the date and time
      of each albuterol actuation. Self-reported COPD exacerbations and healthcare
      utilization were assessed monthly. We used generalized estimating equations with
      a logit link to compare the odds of an exacerbation day to a nonexacerbation day
      by the frequency of daily albuterol use. RESULTS: Average daily albuterol use on
      nonexacerbation days varied greatly between patients, ranging from 1.5 to 17.5
      puffs. There were 48 exacerbation events observed in 29 participants during the
      study period, of which 16 were moderate-to-severe exacerbations. During the
      moderate-to-severe exacerbation days, the median value in average daily albuterol
      use increased by 14.1% (interquartile range: 2.7%-56.9%) compared to average
      nonexacerbation days. A 100% increase in inhaler use was associated with
      increased odds of a moderate-to severe exacerbation (odds ratio 1.54; 95% CI:
      1.21-1.97). Approximately 74% of participants reported satisfaction with the
      sensor. CONCLUSIONS: The electronic inhaler sensor was well received in older
      patients with COPD over a 12-week period. Increased albuterol use captured by the
      device was associated with self-reported episodes of moderate-to-severe
      exacerbations.

PMID- 29035121
TI  - Keep your eye on the target.
AB  - This paper provides a historical perspective on the origin and development of
      Target Theory and how its central concepts have influenced the thought processes
      of radiation biologists for almost a century.

PMID- 29035122
TI  - Homogeneity of Aerosol Deposition and Mucociliary Clearance are Improved
      Following Ivacaftor Treatment in Cystic Fibrosis.
AB  - BACKGROUND: Using planar gamma scintigraphy of inhaled radioaerosols, we have
      developed new analytical methods for assessing homogeneity of aerosol deposition
      and time-dependent particle clearance on a pixel-by-pixel basis, and applied them
      to a therapeutic cystic fibrosis (CF) study. METHODS: At baseline and 1 month
      after beginning treatment with ivacaftor, a cystic fibrosis transmembrane
      regulator modulator for CF patients with at least one copy of the G551D mutation
      (n = 13), initial deposition and subsequent mucociliary clearance (MCC) of
      radiolabeled particles (99mTechnetium-sulfur colloid, 5 MUm mass median
      aerodynamic diameter) inhaled under controlled breathing conditions were
      measured. RESULTS: Improved homogeneity of deposition, that is, decreased areas
      of higher and lower particle deposition in the lungs, was observed following
      ivacaftor treatment. The mean number ratio (NR) of pixels with higher deposition,
      relative to lung size, decreased from 0.14 to 0.09 (p = 0.003) and mean NR of
      colder pixels decreased from 0.23 to 0.19 (p = 0.004). Particle clearance was
      also improved following treatment, with mean MCC through 60 minutes equal to 12%
      versus 24%, without and with treatment, respectively (p = 0.010). Pixel-level
      analysis of MCC showed that (1) the fraction of pixels clearing >30% at 60
      minutes was increased from 0.13 to 0.32 (p = 0.007); and (2) the fraction of
      pixels clearing <5% at 60 minutes was decreased from 0.54 to 0.37 (p = 0.014),
      indicating an overall recruitment of more fast-clearing lung regions with
      ivacaftor treatment. CONCLUSION: These detailed pixel analyses of deposition and
      clearance homogeneity may supplement traditional methods that use large regions
      of interest for assessing efficacy and mechanisms of therapeutic intervention in
      patients with airways disease.

PMID- 29035123
TI  - Physiopathology and genetics in aspirin-exacerbated respiratory disease.
AB  - INTRODUCTION: Aspirin-exacerbated respiratory disease (AERD) is a clinical entity
      characterized by hypersensitivity to aspirin leading to asthma and chronic
      rhinosinusitis with nasosinusal polyposis. The pathophysiology of the disease
      involves disruption at the level of arachidonic acid metabolism. Therefore,
      genetic association studies have been focused on the genes coding this pathway.
      As other mechanisms involved in the genesis of the disease were elucidated, the
      corresponding genes were also explored. AIM: To describe the association reported
      in the literature between gene polymorphisms involved in the pathophysiology or
      therapeutic processes of AERD. RESULTS: There is a genetic association between
      polymorphisms of genes involved in the synthesis of proteins related to
      arachidonic acid metabolism (LTC4S, ALOX5), antigen presentation (HLA),
      inflammation (IL5, IL17), and aspirin metabolism (CYP2C19). CONCLUSIONS: Genetic
      association research in AERD has evaluated studies of SNPs in metabolic pathways
      related to arachidonic acid. Recently, whole genome analysis strategies have
      allowed the detection of new genetic variants that were previously not
      considered. Furthermore, these studies have identified SNPs that are associated
      with inflammatory processes, which could serve as diagnostic markers or
      predictors of the therapeutic response.

PMID- 29035124
TI  - Pain and Alcohol Use among Latinos in Primary Care: Examining Rumination as an
      Explanatory Factor.
AB  - BACKGROUND: Alcohol is a widely abused substance among Latinos. Yet, little is
      known regarding factors underlying hazardous drinking in this population. Growing
      work has linked pain to hazardous drinking, although highly limited work has
      focused on Latinos. OBJECTIVES: The aim of the current study was to test
      rumination as an underlying mechanism explaining relations between pain severity
      and alcohol use among Latinos. METHODS: Data from 252 low-income Latino adults
      (Mage = 38.7 years, SD = 10.8; 86.1% female) attending a community-based primary
      health care clinic were available. Participants completed measures of pain,
      rumination, and alcohol use. Structural equation modeling was used to evaluate
      the indirect effect of pain severity via rumination on alcohol use. RESULTS: The
      model displayed good fit to the data. There was a statistically significant
      indirect effect of pain severity via rumination on alcohol use.
      Conclusions/Importance: The current findings suggest that rumination may underlie
      associations of pain and alcohol use among Latinos. Future work in primary care
      medical settings may benefit from targeting ruminative thinking among Latinos who
      are experiencing pain to address hazardous drinking.

PMID- 29035125
TI  - Letter re: Reducing emergency department visits utilizing a primary care asthma
      specialty clinic in a high risk patient population.

PMID- 29035126
TI  - Re: Byber et al. in Critical Reviews in Toxicology 2016;46:191-240.

PMID- 29035127
TI  - Healing potential of nanohydroxyapatite, gelatin, and fibrin-platelet glue
      combination as tissue engineered scaffolds in radial bone defects of rats.
AB  - Different biomaterials have been used in orthopedic surgery. Evaluation of
      biomaterials for bone healing promotion has been a wide area of research of the
      orthopedic field. Sixty critical size defects of 5 mm long were bilaterally
      created in the radial diaphysis of 30 rats. The animals were randomly divided
      into six equal groups as empty defect, autograft, nanohydroxyapatite (nHA),
      Gelatin (Gel)-nHA, fibrin-platelet glue (FPG)-nHA, and Gel-FPG-nHA groups (n = 10
      in each group). Radiographs of each forelimb were taken postoperatively on the
      1st day and then at the 28th and 56th days post injury. After 56 days, the rats
      were euthanized and their harvested healing bone samples were evaluated by
      histopathology, scanning electron microscopy, and biomechanical testing. All the
      treated defects demonstrated significantly superior new bone formation,
      remodeling, and bone tissue volume. Moreover, the defects treated with FPG-nHA
      showed significantly higher ultimate load, yield load, and stiffness. The Gel-FPG
      nHA moderately improved bone regeneration that was not close to the autograft in
      some parameters, whereas FPG-nHA significantly improved bone healing closely
      comparable with the autograft group in most parameters. In conclusion, although
      all the nHA-containing scaffolds had some beneficial effects on bone
      regeneration, the FPG-nHA scaffold was more effective in improving the structural
      and functional properties of the newly formed bone and was more osteoinductive
      than the Gel and was comparable to the autograft. Therefore, the FPG can be
      regarded as a promising option to be used in conjunction with mineral scaffolds
      for bone tissue engineering.

PMID- 29035129
TI  - Factors influencing the outcome from ultrasonography-guided fine-needle
      aspiration of benign thyroid cysts and partially cystic thyroid nodules: A
      multicenter study.
AB  - PURPOSE: The effect of ultrasonography (US)-guided fine-needle aspiration (US
      FNA) for the collapse of benign cystic thyroid nodules is still unclear. This
      study aimed to assess the positive response rate following US-FNA of the cystic
      component of thyroid cysts and of partially cystic thyroid nodules (PCTNs), and
      to evaluate the factors influencing the outcome. METHODS: From June to December
      2013, seven radiologists at seven institutions prospectively performed US-FNA on
      320 cystic thyroid nodules in 320 patients. Among them, 179 underwent at least
      one follow-up US examination following US-FNA of the cystic component at each
      institution by the same radiologist. A variety of factors, including US features
      of cystic thyroid nodules, the characteristics of the aspirates, and the follow
      up US findings, were analyzed. RESULTS: Of 179 cystic thyroid nodules, there were
      53 thyroid cysts and 126 PCTNs. Of 179 cystic thyroid nodules, no malignancies
      were detected. On follow-up US, the mean size reduction rate of the cystic
      component was 31.9%, and 102 out of 179 thyroid nodules (57.0%) were assigned to
      the response group. On univariate analysis, the degree of aspiration and time
      interval between US-FNA and the final follow-up US showed the significant
      differences between the response and no response groups. On multivariate
      analysis, the only factor that influenced the outcome was the nodule type. The
      cystic component's positive response rate after simple aspiration was higher in
      the thyroid cysts than in the PCTNs. CONCLUSIONS: US-FNA may be effective at
      collapsing the cystic components of benign thyroid cysts and PCTNs.

PMID- 29035128
TI  - Prospective study of plasma homocysteine, its dietary determinants, and risk of
      age-related macular degeneration in men.
AB  - PURPOSE: Cross-sectional and case-control studies generally support a direct
      association between elevated plasma homocysteine and age-related macular
      degeneration (AMD), but data from prospective studies are limited. We examined
      the prospective relation of plasma homocysteine level, its dietary determinants,
      and risk of AMD in a large cohort of apparently healthy male physicians. METHODS:
      During a mean follow-up of 11.2 years, we identified 146 incident cases of
      visually significant AMD (responsible for a reduction of visual acuity to 20/30
      or worse), and 146 controls matched for age, smoking status, and time of blood
      draw. We measured concentration of homocysteine in blood samples collected at
      baseline using an enzymatic assay. and we assessed dietary intake of B vitamins
      and related compounds betaine and choline with a food frequency questionnaire
      administered at baseline. RESULTS: AMD was not associated with plasma level of
      homocysteine; the multivariable-adjusted odds ratio (OR) of AMD comparing the
      highest and lowest quartile of homocysteine was 1.09 (95% confidence interval
      [95% CI]: 0.52-2.31; p for trend = 0.99). However, AMD was inversely associated
      with quartile of intake of total folate (OR: 0.55; 95% CI: 0.24-1.23; p for trend
      = 0.08), vitamin B6 from food (OR: 0.39; 95% CI: 0.17-0.88; p for trend = 0.01),
      and betaine (OR: 0.53; 95% CI: 0.22-1.27; p for trend = 0.048). CONCLUSIONS:
      These prospective data from a cohort of apparently healthy men do not support a
      major role for homocysteine in AMD occurrence, but do suggest a possible
      beneficial role for higher intake of several nutrients involved in homocysteine
      metabolism.

PMID- 29035130
TI  - Patterns of serologic markers of hepatitis B virus infection and the risk of
      transmission among pregnant women in southwestern Nigeria.
AB  - Hepatitis B virus (HBV) infection is a major health concern in developing
      countries that has a high morbidity and mortality rate. Vertical transmission of
      HBV from mother to child has been identified as a major factor leading to
      chronicity with attendant liver conditions, especially in poor socioeconomic
      settings. This study aims to evaluate the prevalence of serological HBV markers
      among pregnant women in Ibadan southwestern Nigeria and to determine the
      implications for perinatal HBV transmission. This study revealed the presence of
      varied HBV serological patterns of infection or immunity among pregnant women in
      Ibadan, Nigeria, and thus the risk of mother to child transmission.

PMID- 29035131
TI  - RI-002, an intravenous immunoglobulin containing high titer neutralizing antibody
      to RSV and other respiratory viruses for use in primary immunodeficiency disease
      and other immune compromised populations.
AB  - INTRODUCTION: Novel immune globulin (IG) products (RI-002, RI-001) have been
      designed to provide protection against respiratory syncytial virus (RSV) mediated
      respiratory illness while at the same time meeting the manufacturing requirements
      established by FDA for antibody supplementation in immunocompromised subjects.
      Areas covered: This review covers the manufacture and development of both RI-001
      and RI-002, including the selection of plasma donors for IG preparation with high
      titers of anti-RSV antibody, in vitro, and preclinical data in the cotton rat
      model S. hispidus, and clinical trials including Phase II and compassionate use
      studies of RI-001 and a multi-center, pivotal Phase III study of RI-002 in PIDD
      patients. Expert commentary: The data demonstrate that RI-002 is efficacious in
      the prevention and treatment of RSV in preclinical normal and immune suppressed
      animal models and is safe and efficacious in the treatment of patients with
      various forms of primary immunodeficiency disease (PIDD). This product offers
      potential advantages over other available IG's for prophylaxis in
      immunocompromised patients requiring polyclonal immunoglobulin supplementation
      because of its unique antibody composition. In addition to its enhanced
      neutralizing anti-RSV activity and its polyclonal IG composition, there is
      preclinical data to support the use of RI-002 for humoral protection against
      other respiratory pathogens.

PMID- 29035132
TI  - Hybrid Lipid/Polymer Nanoparticles for Pulmonary Delivery of siRNA: Development
      and Fate Upon In Vitro Deposition on the Human Epithelial Airway Barrier.
AB  - BACKGROUND: Nowadays, the downregulation of genes involved in the pathogenesis of
      severe lung diseases through local siRNA delivery appears an interesting
      therapeutic approach. In this study, we propose novel hybrid lipid-polymer
      nanoparticles (hNPs) consisting of poly(lactic-co-glycolic) acid (PLGA) and
      dipalmitoyl phosphatidylcholine (DPPC) as siRNA inhalation system. METHODS: A
      panel of DPPC/PLGA hNPs was prepared by emulsion/solvent diffusion and fully
      characterized. A combination of model siRNAs against the sodium transepithelial
      channel (ENaC) was entrapped in optimized hNPs comprising or not
      poly(ethylenimine) (PEI) as third component. siRNA-loaded hNPs were characterized
      for encapsulation efficiency, release kinetics, aerodynamic properties, and
      stability in artificial mucus (AM). The fate and cytotoxicity of hNPs upon
      aerosolization on a triple cell co-culture model (TCCC) mimicking human
      epithelial airway barrier were assessed. Finally, the effect of siRNA-loaded hNPs
      on ENaC protein expression at 72 hours was evaluated in A549 cells. RESULTS:
      Optimized muco-inert hNPs encapsulating model siRNA with high efficiency were
      produced. The developed hNPs displayed a hydrodynamic diameter of ~150 nm, a low
      polydispersity index, a negative zeta potential close to -25 mV, and a peculiar
      triphasic siRNA release lasting for 5 days, which slowed down in the presence of
      PEI. siRNA formulations showed optimal in vitro aerosol performance after
      delivery with a vibrating mesh nebulizer. Furthermore, small-angle X-ray
      scattering analyses highlighted an excellent stability upon incubation with AM,
      confirming the potential of hNPs for direct aerosolization on mucus-lined
      airways. Studies in TCCC confirmed that fluorescent hNPs are internalized inside
      airway epithelial cells and do not exert any cytotoxic or acute proinflammatory
      effect. Finally, a prolonged inhibition of ENaC protein expression was observed
      in A549 cells upon treatment with siRNA-loaded hNPs. CONCLUSIONS: Results
      demonstrate the great potential of hNPs as carriers for pulmonary delivery of
      siRNA, prompting toward investigation of their therapeutic effectiveness in
      severe lung diseases.

PMID- 29035133
TI  - Genetic Polymorphism and Bottleneck Analysis of Balkhi, Hashtnagri, and Michni
      Sheep Populations Using Microsatellite Markers.
AB  - Pakistan is rich in sheep genetic resources. Balkhi, Hashtnagri, and Michni are
      neighboring sheep populations found in Khyber Pakhtunkhwa province of Pakistan.
      In this study, we analyzed the genetic structures and bottleneck incidents within
      these sheep populations using 31 microsatellite DNA markers. Total numbers of
      116, 100, and 95 alleles, with average numbers of 3.20, 3.26, and 3.74 alleles
      per locus were observed, respectively, in Balkhi, Hashtnagri, and Michni
      population. Mean observed heterozygosity was 0.402 in Balkhi, 0.416 in
      Hashtnagri, and 0.522 in Michni population. All the three sheep populations
      showed significantly high inbreeding. Michni population was found to be in
      mutation drift equilibrium, showing the absence of genetic bottleneck. The data
      of Balkhi and Hashtnagri indicated the presence of genetic bottleneck in these
      populations. These results suggest a moderate level of genetic diversity within
      Michni population that may be useful for breed improvement programs. Hashtnagri
      and Balkhi populations having low within breed genetic variability may contain
      some valuable characteristics that need to be conserved.

PMID- 29035134
TI  - Hand-assisted laparoscopic versus laparoscopic nephrectomy as outpatient
      procedures: a prospective randomized study.
AB  - OBJECTIVES: The aims of this study were to discuss the hand-assisted laparoscopic
      nephrectomy (HALNo) outpatient procedure and compare it to the transperitoneal
      laparoscopic nephrectomy (LNo) outpatient procedure. MATERIALS AND METHODS: A
      prospective, randomized study of 30 patients with renal tumor who were recruited
      between November 2014 and February 2016 was performed. The primary endpoint of
      the study was length of hospital stay (LOS). RESULTS: Fifteen patients received
      HALNo and 15 received LNo, with a male to female ratio of 2:1. The mean age was
      60 years for HALNo and 64 years for LNo (p = 0.62). All patients were discharged
      within 6 h after the operation. The mean +/- SD operation time was 65 +/- 24 min
      [95% confidence limits (CL) 51-79] and 69 +/- 24 min (95% CL 56-83) for HALNo and
      LNo, respectively (p = 0.95). The mean time for which patients stayed at the
      postoperative care unit was 85 +/- 53 min (95% CL 44-126) and 91 +/- 66 min (95%
      CL 54-127) for HALNo and LNo, respectively (p = 0.14). The mean LOS was 220 +/-
      96 min (95% CL 155-284) and 272 +/- 80 min (95% CL 224-320) for HALNo and LNo,
      respectively (p = 0.53). CONCLUSION: HALNo, when performed as an outpatient
      procedure, is safe and feasible for a well-informed, well-educated and well
      selected patient group, and is comparable to LNo regarding postoperative LOS.

PMID- 29035135
TI  - Draft De Novo Genome Sequence of Agapornis roseicollis for Application in Avian
      Breeding.
AB  - In aviculture, lovebirds are considered one of the most popular birds to keep.
      This African parakeet is known for its range of plumage colors and ease to tame.
      Plumage variation is the most important price-determining trait of these birds,
      and also the main selection criterion for breeders. Currently, no genetic
      screening tests for traits of economic importance or to confirm pedigree data are
      available for any of the nine lovebird species. As a starting point to develop
      these tests, the de novo genome of Agapornis roseicollis (rosy-faced lovebird)
      was sequenced, assembled, and annotated. Sequencing was done on the Illumina
      HiSeq 2000 platform and the assembly was performed using SOAPdenovo v2.04. The
      genome was found to be 1.1 Gb in size and 16,044 genes were identified and
      annotated. This compared well with other previously sequenced avian genomes, such
      as the chicken, zebra finch, and budgerigar. To assess genome completeness, the
      number of benchmarking universal single-copy orthologs were identified in the
      genome. This was compared to other previously assembled avian genomes and the
      results indicated that the genome will be useful in the development of genetic
      screening tests to aid lovebird breeders in selecting breeding pairs.

PMID- 29035136
TI  - Functional Identification of Allograft Inflammatory Factor 1-Like Gene in Luning
      Chicken.
AB  - Allograft inflammatory factor-1 (AIF-1) is an inflammation-related protein mainly
      produced by immune cells, such as monocyte/macrophages and activated T
      lymphocytes. It is essential for the survival and proinflammatory activity of
      immune cells. However, the function of AIF-1 in chicken still has not been
      defined. In the present study, AIF-1-like (AIF1L) gene was identified in Luning
      chicken. Bioinformatics analysis revealed that the molecular weight of the
      chicken AIF-1 protein was 16290.8 Da. AIF1L contained a Ca2+ binding EF hand and
      could interact with actin filament. Its transcript was found in all tested
      tissues including spleen, brain, heart, kidney, liver, thymus, bursa of
      Fabricius, lung, and a relative low-level expression was detected in leg muscle.
      Furthermore, AIF1L expression in peripheral blood lymphocyte was depressed in a
      dose-dependent manner with cadmium exposure and peripheral blood lymphocyte
      viability decrease displayed a similar pattern with AIF1L expression. The results
      indicated that newly identified chicken AIF1L might be associated with lymphocyte
      viability.

PMID- 29035137
TI  - A review of mental health treatment dropout by ethnic minority youth.
AB  - A large proportion of treatments in youth mental health care are prematurely
      terminated by the patient. Treatment dropout can have severe consequences. Since
      ethnic minority youth are treated less often for mental disorders than other
      youth, it is important to analyse their risk for dropout and to determine if
      there are ethnicity-specific determinants. This review aimed to provide an
      overview of the findings from empirical studies on child and adolescent therapy
      dropout by ethnic minority and to determine if there were ethnicity-specific
      dropout determinants. An extensive literature search was performed to locate
      relevant journal articles. Identified articles were inspected for relevant
      references and these articles were then included in the meta-analysis. A total of
      27 studies were accepted for analysis. The results showed that ethnic minority
      patients have a higher risk of treatment dropout than ethnic majority patients
      and that dropout rates are ethnically specific. Several differences in dropout
      predictors among the ethnic groups were found. In spite of diverse results,
      review limitations, and the lack of several key variables in the available
      research, some clinical recommendations are made. The review indicates that to
      prevent dropout, therapists should pay attention to variables such as ethnic
      background, therapist-patient ethnic match, and the quality of the therapeutic
      relationship.

PMID- 29035138
TI  - Body weight predicts Nicotinamide N-Methyltransferase activity in mouse fat.
AB  - AIM: Nicotinamide N-methyltransferase (NNMT) is a novel regulator of energy
      homeostasis in adipose tissue. NNMT expression is higher in obese mice than in
      lean mice, and NNMT knockdown prevents diet-induced obesity. Little is known
      about the regulation of enzyme activity during the development of obesity. The
      aim of this study was to analyze NNMT activity in tissues of mice with incipient
      and established obesity. METHODS: A fluorescence-based, sensitive, low-volume,
      high-throughput method was developed to assay NNMT activity. C57BL/6 mice were
      fed a high-fat diet for 4 weeks (incipient obesity) and for 12 weeks (established
      obesity). Tissues and serum were harvested and analyzed. RESULTS: NNMT activity
      was highest in subcutaneous white fat (55.0 uU/mg), followed by epididymal white
      fat (35.6 uU/mg), brown adipose tissue (7.8 uU/mg), liver (7.6 uU/mg), and lung
      (7.3 uU/mg). Little activity was detected in heart, skeletal muscle, and kidney.
      No activity was found in serum samples. Body weight predicted NNMT activity in
      white fat, but not in brown fat or any other tissue, and only in incipient
      obesity. With established obesity, this association was lost. CONCLUSIONS: As
      obesity develops, body weight predicts NNMT activity in white adipose tissue, but
      not in any other tissue, consistent with a specific role of adipose-tissue NNMT
      in the regulation of body weight.

PMID- 29035139
TI  - Novel 17-bp Deletion in KDM1B Gene is Significantly Associated with Testis Weight
      in Male Piglet.
AB  - Lysine-specific demethylase 1B (KDM1B) which plays a crucial role in regulating
      methylation status at lysine 4 of histone 3 is important for male fertility. The
      aim of this study was to explore the KDM1B mRNA expression profiles and to
      identify novel genetic variants of the pig KDM1B gene, as well as to determine
      the association between these variants and testis measurement traits in male
      piglets. The KDM1B mRNA expression profiles indicated that this gene widely
      expressed in all tested organs. In addition, a novel 17-bp deletion
      (NC_010449.4:g.31142_31159delCATGGATAGTAGTTGCT) within KDM1B gene was found.
      Notably, this deletion sequence was inconsistent with the prediction by NCBI.
      Association analysis revealed that the 17-bp indel locus was significantly
      associated with the testis weight in 40-day-old Large White pigs (P < 0.05).
      Furthermore, through bioinformatics analysis, transcriptional factor heat shock
      factor-1 could combine the 17-bp sequence. These results not only extend the
      genetic variations of the pig KDM1B gene but also contribute to implementing
      marker-assisted selection in pig breeding.

PMID- 29035140
TI  - Cytoskeleton Genes Expression and Survival Rate Comparison Between Immature and
      Mature Yak Oocyte After OPS Vitrification.
AB  - This study was conducted to investigate the effect of vitrification on survival
      rate and cytoskeleton gene expression during yak oocyte maturation. The yak
      oocytes were incubated for 0 h [germinal vesicle (GV) stage] and in vitro matured
      for 24 h [metaphase II (MII) stage] to obtain immature and mature oocytes.
      Survival rate after vitrification were compared between immature and mature yak
      oocytes and cytoskeleton-related genes [cytokeratin 8 (CK8), beta-actin (ACTB),
      and gap junction protein, alpha 1 (GJA1)] were tested by real-time PCR. Our
      results showed that MII stage survival rate after open pulled straw vitrification
      (35.60%) is significantly higher than GV stage (25.90%) oocytes. Furthermore,
      expression of CK8, ACTB, and GJA1 in MII stage oocytes are also significantly
      higher than GV stage oocytes. In conclusion, our study demonstrated that higher
      expression of GJA1, CK8, and ACTB in vitrify-warmed MII stage oocytes when
      compared with GV stage oocytes and such discrepancy might result in higher
      survival rate in vitrify-warmed MII stage oocytes.

PMID- 29035141
TI  - Usual Care for Maltreatment-Related Pediatric Posttraumatic Stress Disorder in
      Germany.
AB  - Child maltreatment represents a major risk factor for the development of
      emotional and behavioral problems, especially posttraumatic stress disorder
      (PTSD). While effective trauma-focused treatments are available, little is known
      about the usual mental healthcare for abused youths in Germany. The present study
      compared the utilization of mental healthcare in abused youths who had developed
      a PTSD (N = 95) with a group presenting other mental disorders (N = 146).
      Semistructured interviews were used to assess maltreatment histories, current
      mental health, and healthcare utilization. In addition, potential child factors
      associated with access to mental healthcare (age and level of functioning) were
      examined. Results showed that 65 % of both diagnostic groups currently fail to
      use any mental healthcare service. Of the participants with PTSD, 43 (45 %) had
      never received any mental healthcare intervention. Investigations on potential
      barriers are necessary to close the huge gap between clinical services and
      evidence-based, trauma-focused interventions.

PMID- 29035142
TI  - Distribution of the CD4 Alleles in Sus scrofa Demonstrates the Genetic Profiles
      of Western Breeds and Miniature Pigs.
AB  - Widely used antipig CD4 monoclonal antibodies (mAbs) fail to recognize CD4
      alleles characteristic of miniature pig lines such as the National Institutes of
      Health (NIH) miniature pigs and microminipigs. We surveyed polymorphisms in the
      coding sequence of the porcine CD4 gene among Western and Oriental pig breeds and
      Japanese wild boars and investigated their distribution. Of the 13 alleles that
      we identified among the 47 animals, 2 in group I and 3 in group II were found
      exclusively in Western breed pigs. Group IV alleles, which included mAb
      nonbinding alleles, were found frequently in Oriental breed pigs, suggesting that
      the mAb-nonbinding allele arose from the gene pool of Oriental pigs. Group IV
      alleles were also found in Duroc and Large White pigs, suggesting genetic inflow
      from Oriental pig breeds into Western breeds. Comparison of the CD4 sequences of
      species in Cetartiodactyla suggested that the group IV alleles in Sus scrofa
      occurred before the divergence of this species from the other artiodactyls. The
      different antibody specificities of the various CD4 alleles may facilitate the
      discrimination of T-cell populations in transplantation studies using miniature
      pigs. The significance of the preservation of CD4 polymorphisms to immune
      function in pigs warrants further investigation.

PMID- 29035143
TI  - The contribution of glyphosate to agriculture and potential impact of
      restrictions on use at the global level.
AB  - This study assesses the potential economic and environmental impacts that would
      arise if restrictions on glyphosate use resulted in the world no longer planting
      genetically modified herbicide tolerant (GM HT) crops. 'First round' impacts are
      the loss of farm level and aggregate impacts associated with the widespread use
      of GM HT crops (tolerant to glyphosate). There would be an annual loss of global
      farm income gains of $6.76 billion and lower levels of global soybean, corn and
      canola production equal to 18.6 million tonnes, 3.1 million tonnes and 1.44
      million tonnes respectively. There would be an annual environmental loss
      associated with a net increase in the use of herbicides of 8.2 million kg of
      herbicide active ingredient (+1.7%), and a larger net negative environmental
      impact, as measured by the environmental impact quotient (EIQ 11 Kovach J et al1.
      ) indicator of a 12.4%. Also, there would be additional carbon emissions arising
      from increased fuel usage and decreased soil carbon sequestration, equal to the
      equivalent of adding 11.77 million cars to the roads. Global welfare impacts
      based on these farm level impacts (identified through use of the Computable
      General Equilibrium (CGE) model GTAP-BIO) point to global production of soybeans
      and rapeseed falling by 3.7% and 0.7% respectively, partially offset by increases
      in other oilseeds (notably palm oil).  World prices of all grains, oilseeds and
      sugar are expected to rise, especially soybeans (+5.4%) and rapeseed (+2%). The
      welfare impacts are mostly negative, with global welfare falling by $7,408
      million per year. Land use changes will arise, with an additional cropping area
      of 762,000 ha, of which 53% derives from new land brought into cropping
      agriculture, including 167,000 of deforestation. These land use changes are
      likely to induce the generation of an additional 234,000 million kg of carbon
      dioxide emissions.

PMID- 29035144
TI  - Risk factors for multiple suicide attempts among Roma in Hungary.
AB  - In recent years, suicide rates in Hungary have been among the highest in the
      European Union. Attempted suicide rates in the Roma population are 2-3 times
      higher than in the non-Roma population. Since individuals making multiple
      attempts have a higher pro-bability of eventual death by suicide, and there are
      limited data on suicidal behaviour of the Roma population, the aim of this study
      was to explore the sociodemographic and psychological background factors of
      multiple suicide attempts in the Hungarian Roma population. Semistructured
      interviews were conducted with 150 individuals admitted to hospital toxicology
      departments, who made suicide attempts by deliberate self-poisoning, 65 of whom
      were multiple attempters. Detailed information regarding the current attempt and
      previous suicidal acts was recorded. Patients also completed the Shortened Beck
      Depression, the Beck Hopelessness Questionnaire, and the Social Support
      Questionnaire. Independent samples t-tests were used to evaluate differences in
      psychological variables between the Roma ( N = 90) and non-Roma ( N = 60) groups.
      Stepwise linear regression and odds ratios analyses were performed to identify
      potential background factors of multiple suicide attempts. There was a
      significantly higher level of previous suicidal events among the Roma in the
      sample population (3.53 vs. 0.84, p < .001). Roma ethnicity was found to be a
      strong predictor of multiple suicide attempts. Current major depression,
      hopelessness, and diagnosed mood disorder were identified as significant risk
      factors of repeated attempts. Smoking (OR = 5.4), family history of suicide (OR =
      4.9), and long-term unemployment (OR = 4.6) were additional risk factors among
      Roma patients. A thorough understanding of the ethnicity-specific risk factors
      for multiple suicide attempts could facilitate the development of effective
      intervention and postvention programmes.

PMID- 29035145
TI  - Reflecting on how we remember the personal past: missing components in the study
      of memory appraisal and theoretical implications.
AB  - The current paper offers a selective review of the study of memory appraisal,
      focusing on recollections of the personal past, with the goal to bring attention
      to a missing component in this study. To date, memory appraisal studies have
      concentrated on participants' assessments of the content of their personal
      recollections (e.g., their perceptual detail and story-like feel), including
      beliefs about the accuracy of that content. Participants' assessments of
      reflection processes accompanying their recollections (e.g., a sense of piecing
      together recollection fragments) have yet to be extensively examined. The lack of
      information on process-based appraisals is related to prior studies' procedural
      constraints (e.g., kinds of cue prompts and their timing, minimal opportunities
      for reflection). Reasons for addressing this missing component provide the
      central themes of the paper. The reasons emerge from the analysis of
      autobiographical cueing studies, including integration of narrative research
      studies and autobiographical works. The analysis leads to suggestions for future
      research involving the use of personal narratives that are intended to address
      critiques of reconstruction accounts and unresolved questions in the study of
      memory appraisal.

PMID- 29035146
TI  - Moral and legal dilemmas in the policing of protest and other major public
      events.

PMID- 29035147
TI  - Isolation, production, and characterization of a new single chain anti-idiotypic
      antibody against benzo[a]pyrene.
AB  - : Polycyclic aromatic hydrocarbons are chemical carcinogens which could induce
      the development of human cancers. Anti-idiotypic antibodies against
      benzo[a]pyrene (BP) are perspective for human cancer immunoprophylaxis and tumor
      immunodiagnostic techniques. The purpose of this study was to isolate anti
      idiotypic antibodies against BP from human lymphocytes naive phage library. The
      anti-idiotypic antibody, named B5, was selected. Analysis of the nucleotide and
      amino acid sequences B5 showed no similarity to known protein databases
      antibodies. B5 bound idiotypic antibodies against BP in direct and competitive
      ELISA. It was suggested that the B5 carried an immunological image of BP and
      bound the idiotypic antibodies against BP. ABBREVIATIONS: scFv: single-chain
      variable fragment; Ab1: idiotypic antibodies; Ab2: anti-idiotypic antibodies;
      CBD: cellulose binding domain; BSA: bovine serum albumin; PBS: phosphate buffer;
      BP-BSA: benzo[a]pyrene-BSA conjugate; Cr-BSA: chrysene-BSA conjugate; Py-BSA:
      pyrene-BSA conjugate; Ac-BSA: anthracene-BSA conjugate; Ba-BSA: benz[a]anthracene
      BSA conjugate; PAH: polycyclic aromatic hydrocarbons; pSh: mouse idiotypic single
      chain variable fragment against benzo[a]pyrene; T72: human idiotypic single-chain
      variable fragment against benzo[a]pyrene.

PMID- 29035150
TI  - Enhancement of carotenoids and lipids production by oleaginous red yeast
      Sporidiobolus pararoseus KM281507.
AB  - Bioconversion of biodiesel-derived crude glycerol into carotenoids and lipids was
      investigated by a microbial conversion of an oleaginous red yeast Sporidiobolus
      pararoseus KM281507. The methanol content in crude glycerol (0.5%, w/v) did not
      show a significant effect on biomass production by strain KM281507. However,
      demethanolized crude glycerol significantly supported the production of biomass
      (8.64 +/- 0.13 g/L), lipids (2.92 +/- 0.03 g/L), beta-carotene (15.76 +/- 0.85
      mg/L), and total carotenoids (33.67 +/- 1.28 mg/L). The optimal conditions
      suggested by central composite design were crude glycerol concentration (55.04
      g/L), initial pH of medium (pH 5.63) and cultivation temperature (24.01 degrees
      C). Under these conditions, the production of biomass, lipids, beta-carotene, and
      total carotenoids were elevated up to 8.83 +/- 0.05, 4.00 +/- 0.06 g/L, 27.41 +/-
      0.20, and 53.70 +/- 0.48 mg/L, respectively. Moreover, an addition of olive oil
      (0.5 - 2.0%) dramatically increased the production of biomass (14.47 +/- 0.15
      g/L), lipids (6.40 +/- 0.09 g/L), beta-carotene (54.43 +/- 0.95 mg/L), and total
      carotenoids (70.92 +/- 0.51 mg/L). The oleic acid content in lipids was also
      increased to 75.1% (w/w) of total fatty acids, indicating a good potential to be
      an alternative biodiesel feedstock. Meanwhile, the beta-carotene content in total
      carotenoids was increased to 76.7% (w/w). Hence, strain KM281507 could be a good
      potential source of renewable biodiesel feedstock and natural carotenoids.

PMID- 29035148
TI  - Treatment of pulmonary fibrosis with siRNA against a collagen-specific chaperone
      HSP47 in vitamin A-coupled liposomes.
AB  - BACKGROUND: Pulmonary fibrosis is a life-threatening pathological state of
      progressive interstitial lung diseases, such as idiopathic pulmonary fibrosis.
      Myofibroblasts are known to play a critical role in the pathogenesis of pulmonary
      fibrosis. This study aimed to evaluate the inhibitory effect of a small
      interfering RNA (siRNA) on a collagen-specific chaperone heat shock protein 47
      (HSP47). The siRNA was preferentially delivered to myofibroblasts in a bleomycin
      (BLM)-induced pulmonary fibrosis rat model using siRNA against HSP47,
      encapsulated in a vitamin A-coupled liposome (VA-lip-siRNA HSP47). METHODS AND
      RESULTS: Male Sprague-Dawley rats were treated with an intratracheal injection of
      BLM or phosphate buffered saline followed by an intravenous injection of VA-lip
      siRNA HSP47 three times per week under preventive administration schedules from
      day 1 to day 21 and therapeutic administration schedules from day 15 to day 35.
      The expression of HSP47 after the treatment was assessed by immunoblotting. The
      specific delivery of VA-lip-siRNA HSP47 conjugated with 6'-carboxyfluoresce into
      myofibroblasts was examined by immunofluorescence staining. The effect of VA-lip
      siRNA HSP47 on fibrosis was analyzed by morphological and biochemical methods.
      Preferential delivery of VA-lip-siRNA HSP47 to myofibroblasts in fibrotic areas
      in BLM-treated rats was verified by immunofluorescence staining. Treatment of VA
      lip-siRNA HSP47 clearly suppressed HSP47 expression and induced apoptosis of
      myofibroblasts in the lung of BLM-treated rats. Hydroxyproline levels and
      inflammatory cytokines in the lungs, and the number of inflammatory cells in the
      bronchial alveolar lavage of BLM-treated rats were significantly suppressed by
      the treatment. Morphological assessment showed that VA-lip-siRNA HSP47 also
      significantly improved the morphological pulmonary fibrosis of BLM-treated rats
      in both preventive and therapeutic schedules. CONCLUSIONS: These results suggest
      that VA-lip-siRNA HSP47 improves pulmonary fibrosis in not only preventive, but
      also therapeutic schedules, and thus, this drug delivery system should provide a
      novel therapy for refractory pulmonary fibrosis.

PMID- 29035152
TI  - Empirically derived classes of eating pathology in male and female college
      students.
AB  - BACKGROUND: The empirical structure of eating disorder (ED) pathology has often
      been studied in female, clinical samples, leaving questions about the structure
      of ED pathology in males and nonclinical samples. METHOD: A latent class analysis
      was performed on data combined from two different studies (N = 1,751) using the
      behavioral items in the Eating Disorder Examination Questionnaire (EDE-Q; binge
      eating, self-induced vomiting, laxative use, and excessive exercise), with the
      addition of an item representing restraint. Validation analyses examined weight,
      shape, and eating concern among the classes. RESULTS: Three similar classes
      emerged for both the men and women's models: very low ED behaviors, binge eating,
      and high ED behaviors. DISCUSSION: These results suggest that binge eating occurs
      within the context of lower symptom and higher symptom presentations, and that
      the empirical structure of ED symptoms does not differ in men and women in the
      nonclinical population. Further research is needed to clarify whether ED
      phenotypes differ in men and women.

PMID- 29035153
TI  - Acute and Chronic Kidney Injury in a Non-Human Primate Model of Partial-Body
      Irradiation with Bone Marrow Sparing.
AB  - The development of medical countermeasures against acute and delayed multi-organ
      injury requires animal models predictive of the human response to radiation and
      its treatment. Late chronic injury is a well-known feature of radiation
      nephropathy, but acute kidney injury has not been reported in an appropriate
      animal model. We have established a single-fraction partial-body irradiation
      model with minimal marrow sparing in non-human primates. Subject-based medical
      management was used including parenteral fluids according to prospective
      morbidity criteria. We show herein that 10 or 11 Gy exposures caused both acute
      and chronic kidney injury. Acute and chronic kidney injury appear to be dose
      independent between 10 and 11 Gy. Acute kidney injury was identified during the
      first 50 days postirradiation and appeared to resolve before the occurrence of
      chronic kidney injury, which was progressively more severe up to 180 days
      postirradiation, which was the end of the study. These findings show that
      mitigation of the acute radiation syndrome by medical management will unmask
      delayed late effects that occur months after partial-body irradiation. They
      further emphasize that both acute and chronic changes in kidney function must be
      taken into account in the use and timing of mitigators and medical management for
      acute radiation syndrome and delayed effects of acute radiation exposure (DEARE).

PMID- 29035154
TI  - Ethnographic research in immigrant-specific drug abuse recovery houses.
AB  - Access to study populations is a major concern for drug use and treatment
      researchers. Spaces related to drug use and treatment have varying levels of
      researcher accessibility based on several issues, including legality, public
      versus private settings, and insider/outsider status. Ethnographic research
      methods are indispensable for gaining and maintaining access to hidden or "hard
      to-reach" populations. Here, we discuss our long-term ethnographic research on
      drug abuse recovery houses created by and for Latino migrants and immigrants in
      Northern California. We take our field work experiences as a case study to
      examine the problem of researcher access and how ethnographic strategies can be
      successfully applied to address it, focusing especially on issues of entree,
      building rapport, and navigating field-specific challenges related to legality,
      public/private settings, and insider/outsider status. We conclude that continued
      funding support for ethnography is essential for promoting health disparities
      research focused on diverse populations in recovery from substance use disorders.

PMID- 29035155
TI  - Effects of social and spatial contexts on young latinas' methamphetamine use
      initiation.
AB  - In this article, we examine methamphetamine (meth) use initiation as influenced
      by Latinas' social positions within institutions (e.g., family and economy). We
      conducted ethnographic fieldwork in five women's residential substance use
      treatment facilities in Los Angeles County with women who considered meth to be
      their primary drug of choice. Using an urban ethnographic framing, we demonstrate
      the effects of low-income young Latinas' spatial- and social-context rendered
      vulnerability to abuse and neglect, and the resulting emotional distress, on meth
      use initiation. When considering pathways to substance use intervention for
      vulnerable Latina girls and women, clinicians, researchers, and policy makers
      need to understand substance use pathways as dynamic processes to cope with
      psychosocial stress while living in communities with easy access to illicit
      substances such as methamphetamine.

PMID- 29035156
TI  - CD4+ T Memory Stem Cells Correlate with Disease Progression in Chronically HIV-1
      Infected Patients.
AB  - Recently identified T memory stem (Tscm) cells have stem-cell-like properties,
      including long lifespan, self-renewal capacity, and multipotency to differentiate
      into other memory T cell types. In the study of simian immunodeficiency virus
      (SIV) infection, selective depletion of CCR5+CD4+ Tscm cells and the high
      proliferation rate of these cells are believed to be responsible for the
      pathogenesis of SIV-infected rhesus macaques. Here, we conducted a cohort study
      to investigate the influence of chronic human immunodeficiency virus (HIV)-1
      infection on CD4+ Tscm cell homeostasis, and the effect of antiretroviral therapy
      (ART) on CD4+ Tscm cells. Chronic HIV-1 infection resulted in a decrease of the
      CD4+ Tscm cell proportion in HIV-1 patients. The decreased number of CD4+ Tscm
      cells in HIV-1 patients correlated positively with that of circulating CD4+ T
      cells. Further, the depletion of CD4+ Tscm cells was inversely correlated with an
      increased level of T cell immune activation during chronic HIV-1 infection.
      Prolonged ART recovered the CD4+ Tscm cells, and the dynamic change of CD4+ Tscm
      cells was in parallel with CD4+ T cell restoration and a decrease in the level of
      T cell immune activation. We propose that the abnormity of CD4+ Tscm cells may
      contribute to the pathogenesis and disease progression in HIV-1-infected
      individuals.

PMID- 29035157
TI  - Evaluation of serum levels of C3 and C4 complement factors in patients with beta
      thalassemia major in Khuzestan Province, Southwest Iran.
AB  - BACKGROUND AND OBJECTIVES: Thalassemia syndrome is the most common genetic
      disorder in the world and infection is the second cause of death in these
      patients. Measurement of serum C3 and C4 complement factors in serum was done in
      60 patients with beta thalassemia major in comparison with 30 healthy subjects as
      control group. MATERIALS AND METHODS: The serum level of C3 and C4 complement
      factors in 60 patients with beta thalassemia major who were randomly selected
      from among the patients referred to Shafa Hospital of Ahvaz was evaluated and
      compared with 30 samples from healthy individuals with no history of recent
      infectious or autoimmune diseases. It should be noted that single-radial
      immunodiffusion assay was used in this study. RESULTS: This study has shown a
      significant reduction in serum levels of C3 and C4 in patients compared to
      controls (P value < 0.05). DISCUSSION: Decreased synthesis or increased
      consumption of complement factors in patients receiving multiple blood
      transfusions might lead to continuous contact between the immune system and
      various antigens, causing nonstop use of complement factors, recurrent
      infections, changes in parameters of the immune system due to iron overload as
      well as exposure to infectious factors such as HBV, HCV, HIV, and HTLV through
      blood transfusion.

PMID- 29035158
TI  - Humanizing folk devils using ethnography.
AB  - The sociological concepts of the "moral panic" and the deviant "folk devil" apply
      to the drug panics in the United States over methamphetamine, heroin, and crack
      cocaine. Mothers or pregnant women who smoke crack cocaine, and their babies, are
      assigned exaggerated "demonic" attributes that result in stigma and societal
      rejection. Otherwise, ethnographic studies of drug users demonstrate realities
      that are other than what might be considered were one to merely look at their use
      and the consequences. These considerations are examined with respect to the image
      of folk devils, methadone program attendees, smokers of "blunts," opium den
      habitues, and others grouped together as negative influences as a result of their
      drug habits.

PMID- 29035159
TI  - Unintended consequences of local alcohol restrictions in rural Alaska.
AB  - Since 1981, Alaskans have had the ability to enact by referendum local
      restrictions in alcohol sales, importation, and possession, known as "local
      options." Intended to empower rural communities to reduce alcohol abuse and
      associated violence and trauma, the "local option" laws have led to unintended
      consequences as individuals in alcohol-restricted communities seek intoxication
      from both legal and illegal sources of alcohol. Based on 68 interviews with 72
      community members in eight rural sites in Alaska, this article examines these
      unintended consequences of local options restrictions and provides context to the
      challenges rural communities face in implementing alcohol policies.

PMID- 29035161
TI  - A Concept Analysis of Bear Identity.
AB  - Members of the bear community, a gay male subculture, offer insight into the
      development and purveyance of a gay subculture. Using Walker and Avant's concept
      analysis methodology, concept exploration and a subsequent concept analysis of
      the term bear identity, using existing literature, was conducted to obtain a
      better understanding of the meanings of the term bear identity. CINAHL, Psycinfo,
      Pubmed, Medline, LGBT Life, and ProQuest were employed to identify and examine
      the data surrounding the concept of bear identity. After conducting the
      literature review, an analysis of bear identity emerged that explores
      antecedents, attributes, and possible consequences related to bear
      identification. Lastly, implications for theory, research, and practice are
      discussed.

PMID- 29035160
TI  - Towards malaria control and elimination in Ghana: challenges and decision making
      tools to guide planning.
AB  - Ghana is classified as being in the malaria control phase, according to the
      global malaria elimination program. With many years of policy development and
      control interventions, malaria specific mortality among children less than 5
      years old has declined from 14.4% in 2000 to 0.6% in 2012. However, the same
      level of success has not been achieved with malaria morbidity. The recently
      adopted 2015-2020 Ghana strategic action plan aims to reduce the burden of
      malaria by 75.0%. Planning and policy development has always been guided by
      evidence from field studies, and mathematical models that are able to investigate
      malaria transmission dynamics have not played a significant role in supporting
      policy development. The objectives of this study are to describe the malaria
      situation in Ghana and give a brief account of how mathematical modelling
      techniques could support a more informed malaria control effort in the Ghanaian
      context. A review is carried out of some mathematical models investigating the
      dynamics of malaria transmission in sub-Saharan African countries, including
      Ghana. The applications of these models are then discussed, considering the gaps
      that still remain in Ghana for which further mathematical model development could
      be supportive. Because of the collaborative approach adopted in their
      development, some model examples Ghana could benefit from are also discussed.
      Collaboration between malaria control experts and modellers will allow for more
      appropriate mathematical models to be developed. Packaging these models with user
      friendly interfaces and making them available at various levels of malaria
      control management could help provide the decision making tools needed for
      planning and a platform for monitoring and evaluation of interventions in Ghana.

PMID- 29035162
TI  - Effects of osmolytes on stable UUCG tetraloops and their preference for a CG
      closing base pair.
AB  - Osmolytes have the potential to affect the stability of secondary structure
      motifs and alter preferences for conserved nucleic acid sequences in the cell. To
      contribute to the understanding of the in vivo function of RNA we observed the
      effects of different classes of osmolytes on the UNCG tetraloop motif. UNCG
      tetraloops are the most common and stable of the RNA tetraloops and are
      nucleation sites for RNA folding. They also have a significant thermodynamic
      preference for a CG closing base pair. The thermal denaturation of model hairpins
      containing UUCG loops was monitored using UV-Vis spectroscopy in the presence of
      osmolytes with different chemical properties. Interestingly, all of the osmolytes
      tested destabilized the hairpins, but all had little effect on the thermodynamic
      preference for a CG base pair, except for polyethylene glycol (PEG) 200. PEG 200
      destabilized the loop with the CG closing base pair relative to the loop with a
      GC closing base pair. The destabilization was linear with increasing
      concentrations of PEG 200, and the slope of this relationship was not perturbed
      by changes in the hairpin stem outside of the closing pair. This result suggests
      that in the presence of PEG 200, the UUCG loop with a GC closing base pair may
      retain some preferential interactions with the cosolute that are lost in the
      presence of the CG closing base pair. These results reveal that relatively small
      structural changes may influence how osmolytes tune the stability, and thus the
      function of a secondary structure motif in vivo.

PMID- 29035163
TI  - Uptake and correlates of cervical cancer screening among HIV-infected women
      attending HIV care in Uganda.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected women are at high risk of
      cervical cancer. OBJECTIVE: This study assessed uptake and correlates of cervical
      screening among HIV-infected women in care in Uganda. METHODS: A nationally
      representative cross-sectional survey of HIV-infected women in care was conducted
      from August to November 2016. Structured interviews were conducted with 5198
      women aged 15-49 years, from 245 HIV clinics. Knowledge and uptake of cervical
      screening and human papillomavirus (HPV) vaccination were determined. Correlates
      of cervical screening were assessed with modified Poisson regression to obtain
      prevalence ratios (PRs) using Stata version 12.0. RESULTS: Overall, 94.0% (n =
      4858) had ever heard of cervical screening and 66% (n = 3732) knew a screening
      site. However, 47.4% (n = 2302) did not know the schedule for screening and 50%
      (n = 2409) did not know the symptoms of cervical cancer. One-third (33.7%; n =
      1719) rated their risk of cervical cancer as low. Uptake of screening was 30.3%
      (n = 1561). Women who had never been screened cited lack of information (29.6%; n
      = 1059) and no time (25.5%; n = 913) as the main reasons. Increased likelihood of
      screening was associated with receipt of HIV care at a level II health center
      [adj. PR 1.89, 95% confidence interval (CI) 1.29-2.76] and private facilities
      (adj. PR 1.68, 95% CI 1.16-3.21), knowledge of cervical screening (adj. PR 2.19,
      95% CI 1.78-2.70), where to go for screening (adj. PR 6.47, 95% CI 3.69-11.36),
      and low perception of risk (adj. PR 1.52, 95% CI 1.14-2.03). HPV vaccination was
      2%. CONCLUSIONS: Cervical screening and HPV vaccination uptake were very low
      among HIV-infected women in care in Uganda. Improved knowledge of cervical
      screening schedules and sites, and addressing fears and risk perception may
      increase uptake of cervical screening in this vulnerable population.

PMID- 29035165
TI  - Development of highly sensitive cell-based AKT kinase ELISA for monitoring PI3K
      beta activity and compound efficacy.
AB  - Phosphatidylinositol-3 kinase (PI3K) pathway regulates multiple cellular
      functions involving cell survival, growth, motility proliferation, apoptosis, and
      adhesion. These are deregulated in various diseases such as cancer,
      atherosclerosis, and inflammation. PI3Ks phosphorylate phosphatidylinositol 4,5
      biphosphate (PIP2) yielding phosphatidylinositol 3, 4, 5 triphosphate (PIP3)
      which in turn activate AKT kinase (serine/threonine kinase), the central enzyme
      in regulation of metabolic functions. Due to their implications in disease
      pathophysiology, PI3K/AKT inhibitors became attractive targets for pharmaceutical
      industries. In order to assess the functional response generated by PI3K
      inhibitors, an appropriate cell-based screening system is essential in any
      screening cascade. Here we report the development of highly sensitive in-vitro
      cell-based kinase ELISA which quantifies the phosphorylated AKT kinase (serine
      473) and total AKT kinase directly within the cells upon compound treatment.
      PI3Kbeta overexpressing NIH3T3 cells stimulated by lysophosphatidic acid was used
      for PI3K/Akt pathway activation. Assay performance reliability and robustness
      were determined by percentage coefficient of variation (%CV) and Z factor which
      demonstrated an excellent agreement with assay guidelines. This 96-well plate
      medium throughput assay methodology was used to screen novel molecules and proved
      a commendable tool to study the mechanism of action property and target
      engagement of novel PI3K inhibitors in drug discovery.

PMID- 29035166
TI  - Strengthening expertise for health technology assessment and priority-setting in
      Africa.
AB  - BACKGROUND: Achieving sustainable universal health coverage depends partly on
      fair priority-setting processes that ensure countries spend scarce resources
      wisely. While general health economics capacity-strengthening initiatives exist
      in Africa, less attention has been paid to developing the capacity of
      individuals, institutions and networks to apply economic evaluation in support of
      health technology assessment and effective priority-setting. OBJECTIVE: On the
      basis of international  lessons, to identify how research organisations and
      partnerships could contribute to capacity strengthening for health technology
      assessment and priority-setting in Africa. METHODS: A rapid scan was conducted of
      international formal and grey literature and lessons extracted from the
      deliberations of two international and regional workshops relating to capacity
      building for health technology assessment. 'Capacity' was defined in broad terms,
      including a conducive political environment, strong public institutional capacity
      to drive priority-setting, effective networking between experts, strong research
      organisations and skilled researchers. RESULTS: Effective priority-setting
      requires more than high quality economic research. Researchers have to engage
      with an array of stakeholders, network closely other research organisations,
      build partnerships with different levels of government and train the future
      generation of researchers and policy-makers. In low- and middle-income countries
      where there are seldom government units or agencies dedicated to health
      technology assessment, they also have to support the development of an effective
      priority-setting process that is sensitive to societal and government needs and
      priorities. CONCLUSIONS: Research organisations have an important role to play in
      contributing to the development of health technology assessment and priority
      setting capacity. In Africa, where there are resource and capacity challenges,
      effective partnerships between local and international researchers, and with key
      government stakeholders, can leverage existing skills and knowledge to generate a
      critical mass of individuals and institutions. These would help to meet the
      priority-setting needs of African countries and contribute to sustainable
      universal health coverage.

PMID- 29035167
TI  - Labeling Same-Sex Sexuality in a Tolerant Society That Values Normality: The
      Dutch Case.
AB  - Studies have pointed to a trend in Western societies toward the normalization of
      homosexuality and emerging "post-gayness" among young people, who no longer
      consider their sexual identity meaningful in defining themselves. This article
      takes a closer look at the Dutch case where tolerance is regarded as a national
      virtue, while society remains heteronormative. In 38 interviews with Dutch same
      sex-attracted young people, we investigated the labels they used to describe
      their sexual orientation to reveal what they can tell us about normalization,
      tolerance, and heteronormativity. In their labeling strategies, participants de
      emphasized their sexual identity, othered, and reinforced the hetero/homo binary.
      They preferred labels without connotations to gender expression. While post-gay
      rhetoric was ideologically appealing, its use was not an outcome of their sexual
      orientation having become insignificant; it rather enabled them to produce
      normality. We discuss the findings against the backdrop of "Dutch tolerance,"
      which rests on an ideology of normality.

PMID- 29035168
TI  - Employee health-relevant personality traits are associated with the psychosocial
      work environment and leadership.
AB  - OBJECTIVES: Little is known about personality in relation to assessments of the
      psychosocial work environment and leadership. Therefore the objective of this
      study is to explore possible associations and differences in mean values between
      employee health-relevant personality traits and assessments of the psychosocial
      work environment and leadership behaviors. METHODS: 754 survey responses from ten
      organizations were selected from a large-scale intervention study. The Health
      relevant Personality 5 inventory was used to assess personality. Five dimensions
      of the psychosocial work environment were assessed with 38 items from the
      QPSNordic and 6 items from the Developmental Leadership Questionnaire were used
      to assess leadership behavior. RESULTS: Positive correlations were found between
      Hedonic capacity (facet of Extraversion) and perceptions of the psychosocial work
      environment and leadership behavior. Negative correlations were found for
      Negative affectivity (facet of Neuroticism), Antagonism (facet of Agreeableness),
      Impulsivity (facet of Conscientiousness) and Alexithymia (facet of Openness).
      There were also significant differences in mean values of all work environment
      indicators between levels of health-relevant personality traits. Those with
      higher levels of hedonic capacity had higher (better) perceptions compared to
      those with lower levels. Those with higher levels of negative affectivity had
      lower (worse) perceptions compared to those with lower levels. CONCLUSIONS: The
      findings show a clear association between employee health-relevant personality
      traits and assessments of the psychosocial work environment and leadership
      behavior. Personality can be important to take into consideration for leaders
      when interpreting survey results and when designing organizational interventions.

PMID- 29035169
TI  - Prospective Longitudinal Substance Use Patterns in Patients Preparing for
      Hepatitis C Treatment.
AB  - OBJECTIVES: This study prospectively examined the independent courses of alcohol,
      drugs, and smoking over 18 months in 154 patients preparing for hepatitis C virus
      (HCV) treatment in relation to functioning, negative coping, and satisfaction
      with quality of life in data collected from a randomized controlled trial of
      multiple-family group psychoeducation for patients preparing for HCV treatment.
      Patients with HCV who had consistent abstinence, consistent use, or achievement
      of abstinence after study entry were examined for outcomes pertaining to
      functioning in the context of HCV, negative coping, and satisfaction with quality
      of life. METHODS: Of 309 patients considering treatment for HCV recruited from
      outpatient clinics at two major university medical centers and a Veterans Affairs
      medical center for a randomized controlled trial of a psychoeducation
      intervention, 154 completed baseline, 6-month, and 18-month assessments. The
      assessments included structured diagnostic interviews; questionnaires examining
      functioning, coping, and satisfaction with quality of life; medical record
      review; and urine testing for substances of abuse. For these analyses, substance
      use patterns were determined as consistent abstinence, consistent use, and
      achieving abstinence after study entry for alcohol and drug use and smoking.
      RESULTS: The entire sample generally improved in all of these three outcomes over
      the course of the study. The course of alcohol, drugs, and smoking predicted HCV
      related functioning, negative coping, and satisfaction with quality-of-life
      outcomes over 18 months. Three specific patterns of use (consistent abstinence,
      consistent use, and achievement of abstinence after study entry) of these
      substances diverged in association with outcomes related to functioning, negative
      coping, and satisfaction with quality of life, not only across trajectories over
      time within substance types but also among types of substances. CONCLUSIONS: This
      study's finding that different substances were associated with distinct clinical
      outcomes suggests the need to conceptually unbundle different types of substances
      in managing HCV. Future research is needed to examine the clinical utility of
      further unbundling these substances and also to further investigate effects of
      various amounts of use of these substances.

PMID- 29035171
TI  - Proceedings of Patient Reported Outcome Measure's (PROMs) Conference Oxford 2017:
      Advances in Patient Reported Outcomes Research : Oxford, UK. 8th June 2017.

PMID- 29035170
TI  - Abstracts from the 8th International Conference on cGMP Generators, Effectors and
      Therapeutic Implications : Bamberg, Germany. 23-25 June, 2017.

PMID- 29035173
TI  - One year in review 2017: systemic sclerosis.
AB  - Systemic sclerosis is a rare acquired systemic disease characterised by
      heterogeneous evolution and outcome. Each year novel insights into the
      pathogenesis, diagnosis and treatment of this severe disease have been published.
      We herewith provide our overview of the most significant literature contributions
      published over the last year.

PMID- 29035174
TI  - In male rats, the ability of central insulin to suppress glucose production is
      impaired by olanzapine, whereas glucose uptake is left intact.
AB  - BACKGROUND: Insulin receptors are widely expressed in the brain and may represent
      a crossroad between metabolic and cognitive disorders. Although antipsychotics,
      such as olanzapine, are the cornerstone treatment for schizophrenia, they are
      associated with high rates of type 2 diabetes and lack efficacy for illness
      related cognitive deficits. Historically, this risk of diabetes was attributed to
      the weight gain propensity of antipsychotics, but recent work suggests
      antipsychotics can have weight-independent diabetogenic effects involving unknown
      brain-mediated mechanisms. Here, we examined whether antipsychotics disrupt
      central insulin action, hypothesizing that olanzapine would impair the well
      established ability of central insulin to supress hepatic glucose production.
      METHODS: Pancreatic euglycemic clamps were used to measure glucose kinetics
      alongside a central infusion of insulin or vehicle into the third ventricle. Male
      rats were pretreated with olanzapine or vehicle per our established model of
      acute olanzapine-induced peripheral insulin resistance. Groups included (central
      peripheral) vehicle-vehicle (n = 11), insulin-vehicle (n = 10), insulin
      olanzapine (n = 10) and vehicle-olanzapine (n = 8). RESULTS: There were no
      differences in peripheral glucose or insulin levels. Unexpectedly, we showed that
      central insulin increased glucose uptake, and this effect was not perturbed by
      olanzapine. We replicated suppression of glucose production by insulin (clamp
      relative to basal: 77.9% +/- 13.1%, all p < 0.05), an effect abolished by
      olanzapine (insulin-olanzapine: 7.7% +/- 14%). LIMITATIONS: This study used only
      male rats and an acute dose of olanzapine. CONCLUSION: To our knowledge, this is
      the first study suggesting olanzapine may impair central insulin sensing,
      elucidating a potential mechanism of antipsychotic-induced diabetes and opening
      avenues of investigation related to domains of schizophrenia psychopathology.

PMID- 29035172
TI  - A pUL25 dimer interfaces the pseudorabies virus capsid and tegument.
AB  - Inside the virions of alpha-herpesviruses, tegument protein pUL25 anchors the
      tegument to capsid vertices through direct interactions with tegument proteins
      pUL17 and pUL36. In addition to promoting virion assembly, both pUL25 and pUL36
      are critical for intracellular microtubule-dependent capsid transport. Despite
      these essential roles during infection, the stoichiometry and precise
      organization of pUL25 and pUL36 on the capsid surface remain controversial due to
      the insufficient resolution of existing reconstructions from cryo-electron
      microscopy (cryoEM). Here, we report a three-dimensional (3D) icosahedral
      reconstruction of pseudorabies virus (PRV), a varicellovirus of the alpha
      herpesvirinae subfamily, obtained by electron-counting cryoEM at 4.9 A
      resolution. Our reconstruction resolves a dimer of pUL25 forming a capsid
      associated tegument complex with pUL36 and pUL17 through a coiled coil helix
      bundle, thus correcting previous misinterpretations. A comparison between
      reconstructions of PRV and the gamma-herpesvirus Kaposi's sarcoma-associated
      herpesvirus (KSHV) reinforces their similar architectures and establishes
      important subfamily differences in the capsid-tegument interface.

PMID- 29035176
TI  - Comparing Hospital Processes and Outcomes in California Medicare Beneficiaries:
      Simulation Prompts Reconsideration.
AB  - INTRODUCTION: This article is not a traditional research report. It describes how
      conducting a specific set of benchmarking analyses led us to broader reflections
      on hospital benchmarking. We reexamined an issue that has received far less
      attention from researchers than in the past: How variations in the hospital
      admission threshold might affect hospital rankings. Considering this threshold
      made us reconsider what benchmarking is and what future benchmarking studies
      might be like. Although we recognize that some of our assertions are speculative,
      they are based on our reading of the literature and previous and ongoing data
      analyses being conducted in our research unit. We describe the benchmarking
      analyses that led to these reflections. OBJECTIVES: The Centers for Medicare and
      Medicaid Services' Hospital Compare Web site includes data on fee-for-service
      Medicare beneficiaries but does not control for severity of illness, which
      requires physiologic data now available in most electronic medical records.To
      address this limitation, we compared hospital processes and outcomes among Kaiser
      Permanente Northern California's (KPNC) Medicare Advantage beneficiaries and non
      KPNC California Medicare beneficiaries between 2009 and 2010. METHODS: We
      assigned a simulated severity of illness measure to each record and explored the
      effect of having the additional information on outcomes. RESULTS: We found that
      if the admission severity of illness in non-KPNC hospitals increased, KPNC
      hospitals' mortality performance would appear worse; conversely, if admission
      severity at non-KPNC hospitals' decreased, KPNC hospitals' performance would
      appear better. CONCLUSION: Future hospital benchmarking should consider the
      impact of variation in admission thresholds.

PMID- 29035177
TI  - Use of Epidural Analgesia as an Adjunct in Elective Abdominal Wall
      Reconstruction: A Review of 4983 Cases.
AB  - CONTEXT: Use of epidural analgesia in patients undergoing elective abdominal wall
      reconstruction is common. OBJECTIVE: To assess the impact of epidural analgesia
      in patients undergoing abdominal wall reconstruction. DESIGN: All patients who
      underwent elective ventral hernia repair from 2005 to 2014 were retrospectively
      identified. Patients were divided into two groups by the postoperative use of
      epidural analgesics as an adjunct analgesic method. Preoperative comorbidities,
      American Society of Anesthesiologists status, operative findings, postoperative
      pain management, and venothromboembolic prophylaxis were extracted from the
      database. Logistic regressions were performed to assess the impact of epidural
      use. MAIN OUTCOME MEASURES: Severity of pain on postoperative days 1 and 2.
      RESULTS: During the study period, 4983 patients were identified. Of those, 237
      patients (4.8%) had an epidural analgesic placed. After adjustment for
      differences between groups, use of epidural analgesia was associated with
      significantly lower rates of 30-day presentation to the Emergency Department
      (adjusted odds ratio [AOR] = 0.53, 95% confidence interval [CI] = 0.32-0.87,
      adjusted p = 0.01). Use of epidural analgesia resulted in higher odds of abscess
      development (AOR = 5.89, CI = 2.00-17.34, adjusted p < 0.01) and transfusion
      requirement (AOR = 2.92, CI = 1.34-6.40, adjusted p < 0.01). Use of epidural
      analgesia resulted in a significantly lower pain score on postoperative day 1 (3
      vs 4, adjusted p < 0.01). CONCLUSION: Use of epidural analgesia in patients
      undergoing abdominal wall reconstruction may result in longer hospital stay and
      higher incidence of complications while having no measurable positive clinical
      impact on pain control.

PMID- 29035178
TI  - Patient Perspectives on Communication with Primary Care Physicians about Chronic
      Low Back Pain.
AB  - OBJECTIVES: Chronic low back pain (CLBP) is a common health problem with
      challenges for providing satisfactory care. This study was undertaken to identify
      opportunities to improve key aspects of physicians' communications with CLBP
      affected patients. METHODS: A series of 3 focus groups, each with 7 to 11
      patients with CLBP, were recruited from primary care settings and grouped by risk
      level of reduced function resulting from back pain, to elicit perspectives about
      interactions with their primary care physicians. Analysis of focus group
      transcripts used an iterative process based on a thematic approach and a priori
      concepts. RESULTS: A total of 28 patients participated in the focus groups.
      Patient comments about communicating with physicians around CLBP fit into themes
      of listening and empathy, validating pain experiences, conducting effective CLBP
      assessment, providing clear diagnosis and information, and collaboratively
      working on treatment. Patients shared that physicians can foster positive
      interactions with CLBP-affected patients by sharing personal experiences of
      chronic pain, being truthful about not having all the answers and being clear
      about how patients can benefit from referrals, reviewing the patient's previous
      treatments before beginning conversations about treatment options, providing
      follow-up instructions, giving patients a diagnosis beyond "chronic pain," and
      explaining the role of imaging in their care. CONCLUSION: This study provides
      specific steps that physicians in the US can take to improve physician-patient
      interactions during primary care visits pertaining to CLBP. The findings could
      inform physician training, development of educational materials for patients, and
      future research.

PMID- 29035175
TI  - Lifestyle Medicine: A Brief Review of Its Dramatic Impact on Health and Survival.
AB  - By ignoring the root causes of disease and neglecting to prioritize lifestyle
      measures for prevention, the medical community is placing people at harm.
      Advanced nations, influenced by a Western lifestyle, are in the midst of a health
      crisis, resulting largely from poor lifestyle choices. Epidemiologic, ecologic,
      and interventional studies have repeatedly indicated that most chronic illnesses,
      including cardiovascular disease, cancer, and type 2 diabetes, are the result of
      lifestyles fueled by poor nutrition and physical inactivity.In this article, we
      describe the practice of lifestyle medicine and its powerful effect on these
      modern instigators of premature disability and death. We address the economic
      benefits of prevention-based lifestyle medicine and its effect on our health care
      system: A system on the verge of bankruptcy. We recommend vital changes to a
      disastrous course. Many deaths and many causes of pain, suffering, and disability
      could be circumvented if the medical community could effectively implement and
      share the power of healthy lifestyle choices. We believe that lifestyle medicine
      should become the primary approach to the management of chronic conditions and,
      more importantly, their prevention. For future generations, for our own health,
      and for the Hippocratic Oath we swore to uphold ("First do no harm"), the medical
      community must take action. It is our hope that the information presented will
      inspire our colleagues to pursue lifestyle medicine research and incorporate such
      practices into their daily care of patients. The time to make this change is now.

PMID- 29035180
TI  - Ten-Year Trends in Preventive Service Use Before and After Prostate Cancer
      Diagnosis: A Comparison with Noncancer Controls.
AB  - CONTEXT: Few studies have assessed the longer-term quality of preventive care in
      prostate cancer (PCa) survivors. OBJECTIVE: To compare the rates of preventive
      services among PCa survivors five years before and after diagnosis, to men
      without PCa. DESIGN: Men enrolled in Kaiser Permanente Southern California with
      newly diagnosed PCa (2002-2008) were matched 1:1 to men without a PCa diagnosis
      on age, race, and timing of prostate-specific antigen test (N = 31,180). The use
      of preventive services, including colorectal cancer screening, diabetes tests,
      lipid panels, and influenza and pneumococcal vaccinations was assessed 5 years
      before and after diagnosis (or index date for controls). MAIN OUTCOME MEASURES:
      Relative rates (RRs) of use were calculated for cases and controls separately and
      compared using Poisson regression, adjusting for comorbidities and outpatient
      utilization in 2014. RESULTS: Overall, the rates of preventive services were
      lower among men with PCa vs men without PCa. However, in the 5 years after
      diagnosis, rates of preventive service use for all services were greater among
      PCa survivors vs men without PCa (colorectal cancer: RR = 1.05, 95% confidence
      interval [CI] = 1.01-1.10; lipids: RR = 1.10, 95% CI = 1.08-1.11; hemoglobin A1C:
      RR = 1.17, 95% CI = 1.14-1.19; glucose: RR = 1.24, 95% CI = 1.23-1.26; influenza
      vaccine: RR = 1.05, 95% CI = 1.03-1.07; pneumococcal vaccine: RR = 1.03, 95% CI =
      0.97-1.09). CONCLUSION: Delivery of preventive care improved after PCa diagnosis,
      with survivors receiving comparable preventive care to men without PCa during the
      five years following diagnosis.

PMID- 29035179
TI  - Knee Osteoarthritis: A Primer.
AB  - The purpose of this article is to provide a synopsis of the current medical
      understanding of knee osteoarthritis. We describe the prevalence, causes and
      associated risk factors, symptoms, diagnosis and classification, and treatment
      options. A quiz serves to assist readers in their understanding of the presented
      material.

PMID- 29035181
TI  - Minimizing Medical Radiation Exposure by Incorporating a New Radiation "Vital
      Sign" into the Electronic Medical Record: Quality of Care and Patient Safety.
AB  - There is a clearly perceived and imminent need to decrease unnecessary and
      detrimental exposure to medical ionizing radiation. We propose a new radiation
      "vital sign" that incorporates cumulative radiation exposure to create a risk
      score on the basis of an individualized assessment of potential harm from
      additional exposure to medical radiation. We propose to then tie the risk score
      to real-time, evidence-based, clinical decision support for procedures that use
      ionizing radiation. Additionally, we offer recommendations that minimize
      unnecessary or low-yield uses. Preference is given to approaches and modalities
      that use less or no ionizing radiation and that are medically appropriate,
      acceptable to, and safer for patients.

PMID- 29035183
TI  - Atypical Presentation of Acute Angle-Closure Glaucoma in Maroteaux-Lamy
      Mucopolysaccharidosis with Patent Prophylactic Laser Peripheral Iridotomy: A Case
      Report.
AB  - INTRODUCTION: Maroteaux-Lamy syndrome (MLS) is a rare progressive condition
      characterized by inflammation and scarring of multiple organs. Ocular
      complications caused by anterior segment abnormalities commonly cause visual
      impairment in MLS. Angle-closure glaucoma is one such complication, but there are
      limited data on presentation, workup, and management of this condition. CASE
      PRESENTATION: This case report describes an atypical presentation of acute angle
      closure glaucoma in a patient with MLS despite a prior prophylactic laser
      peripheral iridotomy-which would typically prevent an acute angle-closure attack
      that was patent and intact at the time of angle closure. DISCUSSION: Because of
      severe congenital anterior segment crowding, high axial hyperopia, and constant
      accommodative demand in patients with MLS, we recommend performing two
      prophylactic laser peripheral iridotomies simultaneously in the same eye instead
      of one. The mechanism for this indication differs from that in patients at risk
      of acute angle-closure glaucoma because of lens zonulopathy alone. We hope that
      this case report may help prevent vision loss and optimize quality of life in
      patients with MLS who may be wheelchair-bound but are typically high functioning
      with normal intelligence.

PMID- 29035182
TI  - Induction with Infliximab and a Plant-Based Diet as First-Line (IPF) Therapy for
      Crohn Disease: A Single-Group Trial.
AB  - BACKGROUND: Approximately 30% of patients with Crohn disease (CD) are
      unresponsive to biologics. No previous study has focused on a plant-based diet in
      an induction phase of CD treatment. OBJECTIVE: To investigate the remission rate
      of infliximab combined with a plant-based diet as first-line (IPF) therapy for
      CD. METHODS: This was a prospective single-group trial conducted at tertiary
      hospitals. Subjects included consecutive adults with a new diagnosis (n = 26),
      children with a new diagnosis (n = 11), and relapsing adults (n = 9) with CD who
      were naive to treatment with biologics. Patients were admitted and administered a
      standard induction therapy with infliximab (5 mg/kg; 3 infusions at 0, 2, and 6
      weeks). Additionally, they received a lacto-ovo-semivegetarian diet. The primary
      end point was remission, defined as the disappearance of active CD symptoms at
      week 6. Secondary end points were Crohn Disease Activity Index (CDAI) score, C
      reactive protein (CRP) concentration, and mucosal healing. RESULTS: Two adults
      with a new diagnosis were withdrawn from the treatment protocol because of
      intestinal obstruction. The remission rates by the intention-to-treat and per
      protocol analyses were 96% (44/46) and 100% (44/44), respectively. Mean CDAI
      score (314) on admission decreased to 63 at week 6 (p < 0.0001). Mean CRP level
      on admission (5.3 mg/dL) decreased to 0.2 (p < 0.0001). Mucosal healing was
      achieved in 46% (19/41) of cases. CONCLUSION: IPF therapy can induce remission in
      most patients with CD who are naive to biologics regardless of age or whether
      they have a new diagnosis or relapse.

PMID- 29035184
TI  - The Art of Healing through Narrative Medicine in Clinical Practice: A Reflection.
AB  - The art of medicine has roots that lie deep in developing the biopsychosocial
      connection. Understanding a human body (both its physiology and pathology) along
      with components of emotional and spiritual cores can lead to provision of
      excellent medical care and better outcomes. The harmonization of psychosocial
      consequences of a biological disease is helpful not just for health care
      professionals but also for patients. Where it keeps the empathy and compassion
      alive and results in greater patient satisfaction, it also helps boost the
      physician's morale.Our objective is to reflect on the impact of narrative
      medicine on physician-patient dynamics for health care professionals in a
      clinical setting. This article was written after synthesizing the findings of
      evidence-based literature, retrieved from different sources, along with our own
      reflections on our encounters with patients.One could infer from the evidence
      based research that the practice of narrative medicine improves one's concern and
      understanding toward the patient. This requires more time from the clinician, but
      medical care without compassion and humaneness causes high rates of
      dissatisfaction among both patients and health care practitioners, along with the
      risk of recurrent ailments. Our own patient encounters provide a testimony to
      this inference. The biopsychosocial model carries the same holistic approach
      toward patients. The mainstay of treatment in any domain of medicine should
      contain thoughtfulness for the sufferer rather than sole consideration of the
      suffering.

PMID- 29035185
TI  - Image Diagnosis: Yellow Palms and Soles: Look Beyond the Eyes and Think Beyond
      Hyperbilirubinemia.

PMID- 29035186
TI  - Left Ventricular Noncompaction Cardiomyopathy and Recurrent Polymorphic
      Ventricular Tachycardia: A Case Report and Literature Review.
AB  - INTRODUCTION: Noncompaction cardiomyopathy is a rare phenotype of cardiomyopathy
      associated with severe cardiac arrhythmia and thromboembolic complications. CASE
      PRESENTATION: A 55-year-old woman presented with frank pulmonary edema and
      received a diagnosis of noncompaction cardiomyopathy. DISCUSSION: Left
      ventricular noncompaction cardiomyopathy is increasingly being diagnosed because
      of advances in imaging modalities. It is important to differentiate this new
      phenotype of cardiomyopathy from others because its diagnosis, management, and
      prognosis differ. We reviewed the literature and summarized the diagnostic
      criteria, associated complications, initial and long-term management, and the
      recommendation for family screening.

PMID- 29035188
TI  - Finding Purpose: Honing the Practice of Making Meaning in Medicine.
AB  - Despite decades of advances in diagnosing and treating a broad range of
      illnesses, many changes in our health care system impede true caregiving, leaving
      patients and practitioners dissatisfied and creating an emotional burden for
      practitioners that contributes to the staggering rates of physician burnout.
      Given this dissatisfaction and disconnection, practitioners and patients alike
      can benefit from structured opportunities to explore the expectations,
      assumptions, and emotions that shape our understanding of health and illness, and
      thus our experiences within the health care system. This article demonstrates how
      group discussions of poetry-something that might seem irrelevant to medical
      practice or physical wellness-can foster communication, connection, and
      collective reflection for physicians, interprofessional health care teams, and
      groups that include practitioners, patients, and families, allowing participants
      to once again find meaning in medicine.

PMID- 29035187
TI  - Defecation-Specific Behavior in Children with Functional Defecation Issues: A
      Systematic Review.
AB  - CONTEXT: Atypical defecation habits are common and distressing for children and
      families and can have a major impact on quality of life. Often, no underlying
      factor can be identified, and the defecation disorder is considered functional.
      Current interventions are not successful for up to 50% of children. We suggest
      this high failure rate may be caused by lack of consistency in descriptors of
      behavioral indicators for functional defecation problems. Most investigations and
      descriptors focus on general behavior. There are fewer reports concerning
      defecation-specific behaviors. OBJECTIVE: To develop a thorough inventory of
      defecation-specific behaviors, providing a more informed foundation for
      assessment and intervention. DESIGN: A systematic review of six common databases
      was performed following the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses recommendations. Reference lists of retained articles were screened
      for additional studies. MAIN OUTCOME MEASURES: Content analysis was used to
      classify defecation-specific behaviors into 17 categories. RESULTS: Our search
      yielded 2677 articles; 98 peer-reviewed publications were retained for full-text
      review, and 67 articles were included in the final qualitative synthesis.
      Although there is inconsistency in reported diagnostic criteria, stool
      withholding and manifesting pain on defecation are the most commonly reported
      defecation-specific behaviors. In the studies that included children with autism
      or attention-deficit/hyperactivity disorder, the defecation-specific behaviors
      were not unique to the diagnostic group. CONCLUSION: Consistent use of
      established diagnostic criteria, along with use of behaviors identified through
      this review, lay a foundation for more effective interventions.

PMID- 29035189
TI  - Cancer Screening Reminders: Addressing the Spectrum of Patient Preferences.
AB  - CONTEXT: Health care systems continue to seek evidence about how to optimize the
      efficiency and effectiveness of cancer screening reminders. Annual reminders to
      receive preventive services can be an efficient strategy. OBJECTIVE: To
      understand patient motivators and barriers to cancer screening and preferences
      about reminder strategies. DESIGN: We conducted 11 focus groups among adults
      recommended for cancer screening within Kaiser Permanente Washington. We held
      separate focus groups with women aged 21 to 49 years, women 50 to 75 years, and
      men 50 to 75 years. We used an inductive, validated coding scheme for analysis.
      MAIN OUTCOME MEASURES: Motivators and barriers to obtaining recommended cancer
      screening and general cancer screening reminder content and modality preferences.
      RESULTS: Half of our participants were women aged 50 to 75 years, and 25% were
      men aged 50 to 75 years. Differences by age, sex, insurance status, financial
      status, and health beliefs all drove the participants' preferences for whether
      they seek these recommended services and how and when they wish to be reminded
      about recommended cancer screening. Most participants preferred personalized
      reminders, and many favored receiving reminders less than 3 months before the
      recommended procedure date rather than a consolidated annual reminder. Younger
      participants more commonly requested electronic reminders, such as texts and e
      mails. CONCLUSION: Optimizing cancer screening reminders within a health care
      system involves a multifaceted approach that enables members to request which
      form of reminder they prefer (eg, electronic, paper, telephone) and the timing
      with which they want to be reminded, while staying affordable and manageable to
      the health care system.

PMID- 29035190
TI  - Brain tumor epidemiology in the era of precision medicine: The 2017 Brain Tumor
      Epidemiology Consortium meeting report.
AB  - The Brain Tumor Epidemiology Consortium (BTEC) is an international consortium
      that aims to advance the development of multicenter and interdisciplinary
      collaborations that focus on research related to the etiology, outcomes, and
      prevention of brain tumors. The 18<sup>th</sup> annual BTEC meeting was held in
      Banff, AB, Canada, on June 27 - 29, 2017. The meeting focused on the intersection
      between epidemiology and precision medicine, that is, the use of molecular
      indicators of risk, early disease and prognosis or precision epidemiology. While
      traditional epidemiologic approaches group large numbers of participants for
      statistical power, precision epidemiology is founded on the uniqueness and
      biology of individual disease characteristics. With this in mind, plenary
      speakers described the molecular heterogeneity of adult and pediatric brain
      tumors and how those characteristics are currently being used to guide therapy
      and etiologic research. Rare subtypes and novel mechanisms for recruitment of
      individuals for research on brain tumors were discussed along with concepts and
      methodology related to biological and etiologic heterogeneity. The incorporation
      of relevant molecular classifiers into population registries was emphasized for
      its role in future research endeavors, ensuring the accessibility of such tools
      for researchers and clinicians seeking to improve the lives of individuals with
      brain tumors and those at risk. The next BTEC meeting will be held in Copenhagen,
      Denmark, in June 2018.?.

PMID- 29035191
TI  - IDH-mutant giant cell glioblastoma: A neglected tumor variant?

PMID- 29035192
TI  - Bacillus cereus bacteremia with central nervous system involvement: A
      neuropathological study.
AB  - <i>Bacillus cereus</i> is a widely-distributed, gram-positive or variable, rod
      shaped bacterium frequently considered a contaminant in clinical specimens. It is
      recognized as a potential pathogen inducing self-limiting emetic or diarrheal
      food poisoning or localized infection in immunocompetent patients. True
      <italic>B. cereus</italic> bacteremia is uncommon and mainly observed in fragile
      patients, notably in immunocompromised individuals. We report clinical,
      radiological, and pathological findings of a 64-year-old patient with a history
      of acute myeloid leukemia who initially presented a fever while neutropenic after
      the induction of a second cycle of chemotherapy. He developed <italic>B.
      cereus</italic> bacteremia with invasive infection and a fatal outcome. The
      clinical and radiological data of this case are compared to a previously
      published series of 21 patients from our institution with <italic>B.
      cereus</italic> bacteremia. This study highlights the clinical challenge to
      diagnose <italic>B. cereus</italic> and the importance of the delay between the
      detection of <italic>B. cereus</italic> and the initiation of an effective
      targeted antibiotic therapy. This case presented an aggressive evolution with
      multiple necrotic and hemorrhagic foci in the brain. Upon histological
      examination, <italic>B. cereus</italic> virulence was notably reflected by the
      dissection of blood vessel walls by the bacilli and luminal occlusion, a pattern
      that has not been yet reported.?.

PMID- 29035193
TI  - Renal outcome in IgA nephropathy according to Oxford classification and
      ultrastructural analysis in a Brazilian center?.
AB  - AIMS: Correlate clinical and histologic features with renal outcome in patients
      with biopsy-proven IgA nephropathy (IgAN). MATERIALS AND METHODS: Retrospective
      analysis of records and renal tissue of IgAN patients. Histology was revised
      according to MEST score of Oxford classification. Focal segmental
      glomerulosclerosis (FSGS) features were assessed by light microscopy. Electron
      microscopy review searched for podocyte effacement. RESULTS: 67 patients were
      included, 56.7% men, mean age 34.5 +/- 12.5 years, mean arterial pressure (MAP)
      106 +/- 18 mmHg, estimated glomerular filtration rate (eGFR) 63.32 +/- 43.07
      mL/min/1.73m<sup>2</sup> and proteinuria 3.1 +/- 2.2 g/24 h. M1 was seen in 38
      patients (56.7%), E1 in 12 (17.9%), S1 in 49 (73.1%), T1 in 18 (26.8%), and T2 in
      17 (25.3%). Mean effacement index (EI) was 0.81 +/- 0.18 and did not correlate
      with proteinuria. 27 patients (40.2%) had end-stage renal disease (ESRD) which
      correlated with MAP (p = 0.002), eGFR (p = 0.0003), T1 (p = 0.0008) and T2 (p =
      0.0001), follow-up MAP (p = 0.02) and follow-up proteinuria (p = 0.01 for 1.0 -
      4.0 g/24 h and p = 0.005 for >= 4.0 g/24 h). T score correlated with MAP and
      proteinuria at baseline (p = 0.0001 and 0.0097, respectively) and during follow
      up (p = 0.0001 and < 0.0001, respectively). Podocyte hypertrophy correlated with
      MAP at baseline and during follow-up (p = 0.0046 and 0.0295, respectively). Tip
      lesion correlated with MAP at baseline (p = 0.0228). There was no correlation
      between FSGS features or EI with proteinuria or ESRD. CONCLUSIONS: Our data
      corroborate eGFR, proteinuria, MAP and T score as risk factors for ESRD in IgAN.
      Most patients had diffuse podocyte effacement, probably secondary to factors
      unrelated to proteinuria.?.

PMID- 29035194
TI  - Clinicopathologic characteristics of light chain proximal tubulopathy with light
      chain inclusions involving multiple renal cell types?.
AB  - Light chain proximal tubulopathy (LCPT) associated with plasma cell dyscrasias is
      a rare abnormality, especially cases involving multiple cell types. The aim of
      this study is to explore the characteristics and outcomes of these diseases. We
      comprehensively evaluated the clinical-pathological data, treatment, and outcomes
      of 6 LCPT patients with involvement of multiple cell types. In 3 cases, we found
      that the inclusions largely existed in tubular cells, while in 2 cases they
      coexisted in podocytes and tubular cells, and in 1 case they coexisted in
      histiocytes and tubular cells. The stain features and appearances of inclusions
      were specific and varied. Five patients displayed kappa-light chains with crystal
      formation, while 1 patient displayed a lambda subtype with increased lysosomes
      instead of crystals. Six patients presented with proteinuria, 4 with renal
      insufficiency, and 4 with complete or partial Fanconi syndrome. Our findings
      indicate that tubular cells are the most common location of cytoplasmic
      inclusions. Cases with kappa-light chain storage are more common than lambda, and
      the formation of crystals may be associated with the subtype of light chains.
      Immunoelectron microscopy could be used to increase sensitivity for the detection
      and location of monoclonal light chains. Therefore, these patients have some
      common clinical features with varied pathologic characteristics and prognoses but
      the same subtype of light chains.?.

PMID- 29035195
TI  - Effects of fasting during the month of Ramadan on renal function in patients with
      autosomal dominant polycystic kidney disease?.
AB  - BACKGROUND: In this study, we aimed to examine the impact of fasting during the
      month of Ramadan on autosomal dominant polycystic kidney disease (-ADPKD)
      patients with normal to near-normal glomerular filtration rate (GFR). MATERIALS
      AND METHODS: This was a prospective observational study of patients with ADPKD,
      the majority of whom had normal or near-normal GFR. Patients were divided into
      two groups: the fasting group (FG) and the nonfasting group (NFG). Assessments in
      the NFG were performed 1 week before and 1 month after Ramadan, while FG patients
      were assessed on the last day of fasting in addition to the abovementioned
      visits. The following parameters were checked at each visit: blood pressure (BP),
      weight, sodium, potassium, blood urea nitrogen (BUN), creatinine, calcium,
      phosphorus, glucose, lipid profile, bicarbonate, urine density, 24-hour urine
      volume, 24-hour urine protein, GFR, neutrophil gelatinase-associated lipocalin
      (NGAL), and kidney injury molecule-1 (KIM-1). Kidney function tests were carried
      out on the 7<sup>th</sup> day of fasting in the FG for the identification of
      early kidney damage. RESULTS: Of the overall group of 54 patients, 23 were in FG
      (19 female) and 31 were in NFG (18 female). There were no significant differences
      between the two groups in terms of age, gender, ADPKD duration, and presence of
      hypertension. The mean estimated glomerular filtration rate (eGFR) values of FG
      and NFG were 86.4 +/- 18.5 and 66.1 +/- 36.5 mL/min/1.73m<sup>2</sup>,
      respectively. During the follow-up period, no significant changes occurred in BP,
      weight, creatinine, 24-hour urine volume, NGAL, KIM-1, or GFR in either group (p
      > 0.05), while 24-hour urinary protein was significantly decreased in FG (p <
      0.001). CONCLUSION: A fasting duration of ~ 17 hours a day did not affect renal
      function negatively in patients with early-stage chronic kidney disease due to
      ADPKD. Also, no significant changes occurred in acute renal failure markers.?.

PMID- 29035196
TI  - Thyroid function in patients on continuous ambulatory peritoneal dialysis in
      comparison with chronic kidney disease?.
AB  - BACKGROUND/METHODS: Thyroid function was evaluated in 14 Japanese patients on
      continuous ambulatory peritoneal dialysis (CAPD) with end-stage renal disease
      compared with 11 chronic kidney disease (CKD) stage 1+2 patients (glomerular
      filtration rate >= 60 mL/min/1.73m<sup>2</sup>). RESULTS: The serum free
      triiodothyronine (fT<sub>3</sub>) (2.2 +/- 0.3 pg/mL, p < 0.05) levels were
      lower, and the rate of low triiodothyronine (T<sub>3</sub>) syndrome was higher
      (4 of 13 cases, 30.8%) in the CAPD patients than in the CKD stage 1+2 patients (1
      of 10 cases, 10.0%, respectively) or the 57 age-matched healthy controls. The
      serum thyroglobulin (Tg) levels were significantly higher in the CAPD patients
      (39.7 (13.4 - 178.0) ng/mL) than in the CKD stage 1+2 patients (9.9 (5.5 - 28.8)
      ng/mL, p < 0.05). High serum Tg levels (> 30 ng/mL) were observed in 66.7% of the
      CAPD patients. CONCLUSION: The finding from our study suggested the deterioration
      of thyroid function with higher prevalence of low T<sub>3</sub> syndrome in the
      CAPD patients. Although speculation as to the reasons for this would be unwise at
      this point, we did note that the serum Tg levels were very high in the CAPD
      patients.?.

PMID- 29035197
TI  - Drug-induced kidney injury: A large case series from the Berlin Case-Control
      Surveillance Study?.
AB  - OBJECTIVES: Drug-induced kidney injury (DIKI) may affect patients regardless of
      their baseline kidney function. Therefore, this study evaluated DIKI in patients
      with or without previous chronic kidney disease (CKD). MATERIALS AND METHODS:
      Potential DIKI cases were ascertained using the network of the Berlin Case
      Control Surveillance Study in all 51 Berlin hospitals from April 2010 until
      December 2011. Via face-to-face interviews and medical chart reviews, information
      on all previous drug intake, comorbidities, and demographics was gathered.
      Included were adult patients with a new diagnosis of acute kidney injury or an
      acute-on-chronic kidney injury, and with an at least "possible" drug etiology
      based on the standardized causality assessment of the World Health Organization.
      Excluded were patients with prerenal or postrenal etiology, bacterial
      interstitial nephritis, or previous renal transplantation. RESULTS: Overall, 143
      patients with DIKI were included in the study (mean age 68.4 +/- 15.6 years). Of
      those, 77 (54%) had prediagnosed CKD. The most common symptom at onset was
      anuria/oliguria, while 73 patients (51%) underwent renal replacement therapy, and
      11 patients (8%) died. Cardiovascular drugs, such as furosemide, torasemide,
      hydrochlorothiazide, and ramipril (33%), systemic anti-infectives, such as
      vancomycin (23%), and musculoskeletal drugs, such as ibuprofen and diclofenac
      (15%), were most commonly causal for DIKI. Of the 37 patients with DIKI caused by
      nonsteroidal anti-inflammatory drugs (NSAIDs), 20 (54%) had prediagnosed CKD.
      CONCLUSION: Nephrotoxicity can be caused by numerous medications, highlighting
      the importance of increased vigilance among physicians. Moreover, NSAIDs seem to
      exhibit nephrotoxic properties even in patients with normal baseline kidney
      function.?.

PMID- 29035198
TI  - Affected parent sex and severity of autosomal dominant polycystic kidney disease:
      a retrospective cohort study?.
AB  - OBJECTIVE: Parental inheritance may differentially affect autosomal dominant
      polycystic kidney disease (-ADPKD) severity via genetic imprinting or in utero
      epigenetic modifications; however, evidence is inconsistent. We conducted a
      longitudinal retrospective cohort study to assess the association between sex of
      the affected parent and time to hypertension diagnosis, end-stage renal disease
      (ESRD), and death in patients with the PKD1 genotype. MATERIALS AND METHODS: 814
      individuals who participated in research at the University of Colorado were
      studied. Kaplan-Meier survival analysis was performed. The predictor was parental
      sex, and outcomes were diagnosis of hypertension, progression to ESRD, and death.
      We also examined associations in four strata according to affected parent and
      participant sex, as previous studies have reported earlier onset of ESRD in males
      compared to females. RESULTS: The median follow-up for each outcome was as
      follows: hypertension, 30 (interquartile range (IQR): 18, 37); ESRD, 43 (IQR: 31,
      52), death 39 (IQR: 25, 52) years of age. Among affected offspring in the entire
      cohort, there was no difference in hypertension diagnosis (p = 0.97) or
      progression to ESRD (p = 0.79) according to affected parent sex; however,
      participants with an affected mother were more likely to die than participants
      with an affected father (p < 0.05). In stratified analyses, males were more
      likely than females to develop hypertension and reach ESRD when the affected
      parent was the father (p < 0.01) but not when the affected parent was the mother
      (p >= 0.11). CONCLUSIONS: Our results are largely in contrast to the hypothesis
      that severity of ADPKD is worse with maternal inheritance of disease.?.

PMID- 29035199
TI  - Structure-based nuclear import mechanism of histones H3 and H4 mediated by
      Kap123.
AB  - Kap123, a major karyopherin protein of budding yeast, recognizes the nuclear
      localization signals (NLSs) of cytoplasmic histones H3 and H4 and translocates
      them into the nucleus during DNA replication. Mechanistic questions include H3-
      and H4-NLS redundancy toward Kap123 and the role of the conserved diacetylation
      of cytoplasmic H4 (K5ac and K12ac) in Kap123-mediated histone nuclear
      translocation. Here, we report crystal structures of full-length Kluyveromyces
      lactis Kap123 alone and in complex with H3- and H4-NLSs. Structures reveal the
      unique feature of Kap123 that possesses two discrete lysine-binding pockets for
      NLS recognition. Structural comparison illustrates that H3- and H4-NLSs share at
      least one of two lysine-binding pockets, suggesting that H3- and H4-NLSs are
      mutually exclusive. Additionally, acetylation of key lysine residues at NLS,
      particularly H4-NLS diacetylation, weakens the interaction with Kap123. These
      data support that cytoplasmic histone H4 diacetylation weakens the Kap123-H4-NLS
      interaction thereby facilitating histone Kap123-H3-dependent H3:H4/Asf1 complex
      nuclear translocation.

PMID- 29035200
TI  - Small conductance Ca2+-activated K+ channels induce the firing pause periods
      during the activation of Drosophila nociceptive neurons.
AB  - In Drosophila larvae, Class IV sensory neurons respond to noxious thermal stimuli
      and provoke heat avoidance behavior. Previously, we showed that the activated
      neurons displayed characteristic fluctuations of firing rates, which consisted of
      repetitive high-frequency spike trains and subsequent pause periods, and we
      proposed that the firing rate fluctuations enhanced the heat avoidance (Terada et
      al., 2016). Here, we further substantiate this idea by showing that the pause
      periods and the frequency of fluctuations are regulated by small conductance Ca2+
      activated K+ (SK) channels, and the SK knockdown larvae display faster heat
      avoidance than control larvae. The regulatory mechanism of the fluctuations in
      the Class IV neurons resembles that in mammalian Purkinje cells, which display
      complex spikes. Furthermore, our results suggest that such fluctuation coding in
      Class IV neurons is required to convert noxious thermal inputs into effective
      stereotyped behavior as well as general rate coding.

PMID- 29035201
TI  - Anti-diabetic drug binding site in a mammalian KATP channel revealed by Cryo-EM.
AB  - Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic
      KATP channels composed of SUR1 and Kir6.2. The mechanism by which these drugs
      interact with and inhibit the channel has been extensively investigated, yet it
      remains unclear where the drug binding pocket resides. Here, we present a cryo-EM
      structure of a hamster SUR1/rat Kir6.2 channel bound to a high-affinity
      sulfonylurea drug glibenclamide and ATP at 3.63 A resolution, which reveals
      unprecedented details of the ATP and glibenclamide binding sites. Importantly,
      the structure shows for the first time that glibenclamide is lodged in the
      transmembrane bundle of the SUR1-ABC core connected to the first nucleotide
      binding domain near the inner leaflet of the lipid bilayer. Mutation of residues
      predicted to interact with glibenclamide in our model led to reduced sensitivity
      to glibenclamide. Our structure provides novel mechanistic insights of how
      sulfonylureas and ATP interact with the KATP channel complex to inhibit channel
      activity.

PMID- 29035204
TI  - Four Novel Motion Paradigms Based on Steady-State Motion Visual Evoked Potential.
AB  - OBJECTIVE: The purpose of this paper was to study the applicability of paradigms
      with motion forms for use in a brain-computer interface (BCI). We examined the
      performances of different paradigms and evaluated the stimulus effects. METHODS:
      We designed four novel stimulus paradigms based on basic motion modes: swing,
      rotation, spiral, and radial contraction-expansion. Canonical correlation
      analysis (CCA) was used to analyze the accuracy. Additionally, we optimized CCA
      template signal harmonic combinations for the different motion paradigms.
      RESULTS: The spiral motion paradigm exhibited the highest average information
      transfer rate (ITR) and recognition accuracy (41.24 bit/min-1/95.33%), and the
      average ITRs and recognition accuracies were lowest for the rotation motion
      paradigm (31.89 bit/min-1 /80.89%) and the radial contraction-expansion motion
      paradigm (32.62 bit/min-1 /80.72%) because they include fewer harmonic
      components. CONCLUSION: Any stimulus paradigms with periodic motion can induce
      steady-state motion visual evoked potentials (SSMVEPs), but the SSMVEP harmonic
      components induced by different motion modes differed significantly. The spiral
      motion paradigm was more suitable for BCI applications. SIGNIFICANCE: This study
      is an important extension to the existing SSMVEP-based BCI literature, and
      provides new insight to enable future design of the BCI paradigms.

PMID- 29035203
TI  - Developing a Nonstationary Computational Framework With Application to Modeling
      Dynamic Modulations in Neural Spiking Responses.
AB  - OBJECTIVE: This paper aims to develop a computational model that incorporates the
      functional effects of modulatory covariates (such as context, task, or behavior),
      which dynamically alter the relationship between the stimulus and the neural
      response. METHODS: We develop a general computational approach along with an
      efficient estimation procedure in the widely used generalized linear model (GLM)
      framework to characterize such nonstationary dynamics in spiking response and
      spatiotemporal characteristics of a neuron at the level of individual trials. The
      model employs a set of modulatory components, which nonlinearly interact with
      other stimulus-related signals to reproduce such nonstationary effects. RESULTS:
      The model is tested for its ability to predict the responses of neurons in the
      middle temporal cortex of macaque monkeys during an eye movement task. The fitted
      model proves successful in capturing the fast temporal modulations in the
      response, reproducing the spike response temporal statistics, and accurately
      accounting for the neurons' dynamic spatiotemporal sensitivities, during eye
      movements. CONCLUSION: The nonstationary GLM framework developed in this study
      can be used in cases where a time-varying behavioral or cognitive component makes
      GLM-based models insufficient to describe the dependencies of neural responses on
      the stimulus-related covariates. SIGNIFICANCE: In addition to being quite
      powerful in encoding time-varying response modulations, this general framework
      also enables a readout of the neural code while dissociating the influence of
      other nonstimulus covariates. This framework will advance our ability to
      understand sensory processing in higher brain areas when modulated by several
      behavioral or cognitive variables.

PMID- 29035205
TI  - Multi-Views Fusion CNN for Left Ventricular Volumes Estimation on Cardiac MR
      Images.
AB  - OBJECTIVE: Left ventricular (LV) volume estimation is a critical procedure for
      cardiac disease diagnosis. The objective of this paper is to address a direct LV
      volume prediction task. METHODS: In this paper, we propose a direct volume
      prediction method based on the end-to-end deep convolutional neural networks. We
      study the end-to-end LV volume prediction method in items of the data
      preprocessing, network structure, and multiview fusion strategy. The main
      contributions of this paper are the following aspects. First, we propose a new
      data preprocessing method on cardiac magnetic resonance (CMR). Second, we propose
      a new network structure for end-to-end LV volume estimation. Third, we explore
      the representational capacity of different slices and propose a fusion strategy
      to improve the prediction accuracy. RESULTS: The evaluation results show that the
      proposed method outperforms other state-of-the-art LV volume estimation methods
      on the open accessible benchmark datasets. The clinical indexes derived from the
      predicted volumes agree well with the ground truth ( ${?rm{EDV:R}}^{{?rm
      2}}={?text{0.974}}$, ${?rm{RMSE?,}}= {?text{9.6}}{?rm{?,ml}}$;
      ${?rm{ESV:R}}^{{?rm 2}}={?text{0.976}}$, ${?rm{RMSE}}=
      {?text{7.1}}?,{?text{ml}}$; ${?rm{EF:R}}^{{?rm 2}} ={?text{0.828}}$,
      ${?rm{RMSE}}= {?text{4.71}}?% $). CONCLUSION: Experimental results prove that the
      proposed method may be useful for the LV volume prediction task. SIGNIFICANCE:
      The proposed method not only has application potential for cardiac diseases
      screening for large-scale CMR data, but also can be extended to other medical
      image research fields.

PMID- 29035202
TI  - Localised dynactin protects growing microtubules to deliver oskar mRNA to the
      posterior cortex of the Drosophila oocyte.
AB  - The localisation of oskar mRNA to the posterior of the Drosophila oocyte defines
      where the abdomen and germ cells form in the embryo. Kinesin 1 transports oskar
      mRNA to the oocyte posterior along a polarised microtubule cytoskeleton that
      grows from non-centrosomal microtubule organising centres (ncMTOCs) along the
      anterior/lateral cortex. Here, we show that the formation of this polarised
      microtubule network also requires the posterior regulation of microtubule growth.
      A missense mutation in the dynactin Arp1 subunit causes most oskar mRNA to
      localise in the posterior cytoplasm rather than cortically. oskar mRNA transport
      and anchoring are normal in this mutant, but the microtubules fail to reach the
      posterior pole. Thus, dynactin acts as an anti-catastrophe factor that extends
      microtubule growth posteriorly. Kinesin 1 transports dynactin to the oocyte
      posterior, creating a positive feedback loop that increases the length and
      persistence of the posterior microtubules that deliver oskar mRNA to the cortex.

PMID- 29035206
TI  - Parametric Dependencies of Sliding Window Correlation.
AB  - OBJECTIVE: In this paper, we explore the dependence of sliding window correlation
      (SWC) results on different parameters of correlating signals. The SWC is
      extensively used to explore the dynamics of functional connectivity (FC) networks
      using resting-state functional MRI (rsfMRI) scans. These scanned signals often
      contain multiple amplitudes, frequencies, and phases. However, the exact values
      of these parameters are unknown. Two recent studies explored the relationship of
      window length and frequencies (minimum/maximum) in the correlating signals.
      METHODS: We extend the findings of these studies by using two deterministic
      signals with multiple amplitudes, frequencies, and phases. Afterward, we modulate
      one of the signals to introduce dynamics (nonstationarity) in their relationship.
      We also explore the relationship of window length and frequency band for real
      rsfMRI data. RESULTS: For deterministic signals, the spurious fluctuations due to
      the method itself minimize, and the SWC estimates the stationary correlation when
      frequencies in the signals have specific relationship. For dynamic relationship
      also, the undesirable frequencies were removed under specific conditions for the
      frequencies. For real rsfMRI data, the SWC results varied with frequencies and
      window length. CONCLUSION: In the absence of any "ground truth" for different
      parameters in real rsfMRI signals, the SWC with a constant window size may not be
      a reliable method to study the dynamics of the FC. SIGNIFICANCE: This study
      reveals the parametric dependencies of the SWC and its limitation as a method to
      analyze dynamics of FC networks in the absence of any ground truth.

PMID- 29035207
TI  - Novel Quantitative Analytical Approaches for Rotor Identification and Associated
      Implications for Mapping.
AB  - GOAL: Clinical studies identifying rotors and confirming these sites for ablation
      in treating cardiac arrhythmias have had inconsistent results with the currently
      available analysis techniques. The aim of this study is to evaluate four new
      signal analysis approaches-multiscale frequency (MSF), Shannon entropy (SE),
      Kurtosis (Kt), and multiscale entropy (MSE)-in their ability to identify the
      pivot point of rotors. METHODS: Optical mapping movies of ventricular tachycardia
      were used to evaluate the performance and robustness of SE, Kt, MSF, and MSE
      techniques with respect to several clinical limitations: decreased time duration,
      reduced spatial resolution, and the presence of meandering rotors. To
      quantitatively assess the robustness of the four techniques, results were
      compared to the "true" rotor(s) identified using optical mapping-based phase
      maps. RESULTS: The results demonstrate that MSF, Kt, and MSE accurately
      identified both stationary and meandering rotors. In addition, these techniques
      remained accurate under simulated clinical limitations: shortened electrogram
      duration and decreased spatial resolution. Artifacts mildly affected the
      performance of MSF, Kt, and MSE, but strongly impacted the performance of SE.
      CONCLUSION: These results motivate further validation using intracardiac
      electrograms to see if these approaches can map rotors in a clinical setting and
      whether they apply to more complex arrhythmias including atrial or ventricular
      fibrillation. SIGNIFICANCE: New techniques providing more accurate rotor
      localization could improve characterization of arrhythmias and, in turn, offer a
      means to accurately evaluate whether rotor ablation is a viable and effective
      treatment for chaotic cardiac arrhythmias.

PMID- 29035208
TI  - An Efficient Integral-Based Method for Three-Dimensional MR-EPT and the
      Calculation of the RF-Coil-Induced ${B_z}$ Field.
AB  - Magnetic resonance electrical property tomography (MR-EPT) has significant
      potential for the estimation of the electrical properties (EPs) of tissue, which
      are essential for the calculation of specific absorption rates (SAR), a critical
      safety factor requiring monitoring and controlling in applications of ultrahigh
      field magnetic resonance imaging. In this paper, a novel, efficient method based
      on integral equations is proposed for the calculation of the EPs and the RF-coil
      induced field. An inverse problem framework is first constructed to include the
      forward problem operator, while the EPs are reconstructed by using a nonlinear
      conjugate gradient method. The RF-coil-induced component is then calculated based
      on the achieved EPs and the forward operator. The proposed MR-EPT algorithm
      improves upon and differs from the existing methods in three aspects. First, a
      three-dimensional algorithm with improved efficiency is proposed. The higher
      efficiency arises from using a fast integral equation solver as well as an
      approximation of initial solution. Second, in addition to the EP values, the
      proposed method calculates the RF-coil-induced component, which is usually
      neglected in the existing MR-EPT algorithms. Here, we show that considering this
      field can significantly improve the accuracy of the SAR calculation. Finally, in
      contrast to differential approaches, the proposed method is more robust against
      noisy measurement of the transmit magnetic fields, because of the nature of the
      integral equations. The proposed method is verified through a full-wave
      simulation and an anatomically accurate numerical brain model, demonstrating its
      accuracy and efficiency.

PMID- 29035209
TI  - An Efficient Approach for Accelerating Bucket Elimination on GPUs.
AB  - Bucket elimination (BE) is a framework that encompasses several algorithms,
      including belief propagation (BP) and variable elimination for constraint
      optimization problems (COPs). BE has significant computational requirements that
      can be addressed by using graphics processing units (GPUs) to parallelize its
      fundamental operations, i.e., composition and marginalization, which operate on
      functions represented by large tables. We propose a novel approach to parallelize
      these operations with GPUs, which optimizes the table layout so to achieve better
      performance in terms of increased speedup and scalability. Our approach allows us
      to process incomplete tables (i.e., tables with some missing variables
      assignments), which often occur in several practical applications (such as the
      ones we consider in our dataset). Finally, we can process tables that are larger
      than the GPU memory. Our approach outperforms the state-of-the-art technique to
      parallelize BP on GPUs, achieving better speedups (up to +466% with respect to
      such parallel technique). We test our method on a publicly available COP dataset,
      measuring a speedup up to with respect to the sequential version. The ability of
      our technique to process large tables is crucial in this scenario, in which most
      of the instances generate tables larger than the GPU memory, and hence they
      cannot be solved with previous GPU techniques related to BE.

PMID- 29035210
TI  - Inextensible Non-Rigid Structure-from-Motion by Second-Order Cone Programming.
AB  - We present a global and convex formulation for the template-less 3D
      reconstruction of a deforming object with the perspective camera. We show for the
      first time how to construct a Second-Order Cone Programming (SOCP) problem for
      Non-Rigid Structure-from-Motion (NRSfM) using the Maximum-Depth Heuristic (MDH).
      In this regard, we deviate strongly from the general trend of using affine
      cameras and factorization-based methods to solve NRSfM, which do not perform well
      with complex nonlinear deformations. In MDH, the points' depths are maximized so
      that the distance between neighbouring points in camera space are upper bounded
      by the geodesic distance. In NRSfM both geodesic and camera space distances are
      unknown. We show that, nonetheless, given point correspondences and the camera's
      intrinsics the whole problem can be solved with SOCP. This is the first convex
      formulation for NRSfM with physical constraints. We further present how
      robustness and temporal continuity can be included in the formulation to handle
      outliers and decrease the problem size, respectively. We show with extensive
      experiments that our methods accurately reconstruct quasi-isometric objects from
      partial views under articulated and strong deformations. Compared to the previous
      methods, our approach gives better or similar accuracy. It naturally handles
      missing correspondences, non-smooth objects and is very simple to implement
      compared to previous methods, with only one free parameter (the neighbourhood
      size).

PMID- 29035211
TI  - Error-Correcting Factorization.
AB  - Error Correcting Output Codes (ECOC) is a successful technique in multi-class
      classification, which is a core problem in Pattern Recognition and Machine
      Learning. A major advantage of ECOC over other methods is that the multi-class
      problem is decoupled into a set of binary problems that are solved independently.
      However, literature defines a general error-correcting capability for ECOCs
      without analyzing how it distributes among classes, hindering a deeper analysis
      of pair-wise error-correction. To address these limitations this paper proposes
      an Error-Correcting Factorization (ECF) method. Our contribution is three fold:
      (I) We propose a novel representation of the error-correction capability, called
      the design matrix, that enables us to build an ECOC on the basis of allocating
      correction to pairs of classes. (II) We derive the optimal code length of an ECOC
      using rank properties of the design matrix. (III) ECF is formulated as a discrete
      optimization problem, and a relaxed solution is found using an efficient
      constrained block coordinate descent approach. (IV) Enabled by the flexibility
      introduced with the design matrix we propose to allocate the error-correction on
      classes that are prone to confusion. Experimental results in several databases
      show that when allocating the error-correction to confusable classes ECF
      outperforms state-of-the-art approaches.

PMID- 29035212
TI  - A Deep Cascade of Convolutional Neural Networks for Dynamic MR Image
      Reconstruction.
AB  - Inspired by recent advances in deep learning, we propose a framework for
      reconstructing dynamic sequences of 2-D cardiac magnetic resonance (MR) images
      from undersampled data using a deep cascade of convolutional neural networks
      (CNNs) to accelerate the data acquisition process. In particular, we address the
      case where data are acquired using aggressive Cartesian undersampling. First, we
      show that when each 2-D image frame is reconstructed independently, the proposed
      method outperforms state-of-the-art 2-D compressed sensing approaches, such as
      dictionary learning-based MR image reconstruction, in terms of reconstruction
      error and reconstruction speed. Second, when reconstructing the frames of the
      sequences jointly, we demonstrate that CNNs can learn spatio-temporal
      correlations efficiently by combining convolution and data sharing approaches. We
      show that the proposed method consistently outperforms state-of-the-art methods
      and is capable of preserving anatomical structure more faithfully up to 11-fold
      undersampling. Moreover, reconstruction is very fast: each complete dynamic
      sequence can be reconstructed in less than 10 s and, for the 2-D case, each image
      frame can be reconstructed in 23 ms, enabling real-time applications.

PMID- 29035213
TI  - A Fidelity-Embedded Regularization Method for Robust Electrical Impedance
      Tomography.
AB  - Electrical impedance tomography (EIT) provides functional images of an electrical
      conductivity distribution inside the human body. Since the 1980s, many potential
      clinical applications have arisen using inexpensive portable EIT devices. EIT
      acquires multiple trans-impedance measurements across the body from an array of
      surface electrodes around a chosen imaging slice. The conductivity image
      reconstruction from the measured data is a fundamentally ill-posed inverse
      problem notoriously vulnerable to measurement noise and artifacts. Most available
      methods invert the ill-conditioned sensitivity or the Jacobian matrix using a
      regularized least-squares data-fitting technique. Their performances rely on the
      regularization parameter, which controls the trade-off between fidelity and
      robustness. For clinical applications of EIT, it would be desirable to develop a
      method achieving consistent performance over various uncertain data, regardless
      of the choice of the regularization parameter. Based on the analysis of the
      structure of the Jacobian matrix, we propose a fidelity-embedded regularization
      (FER) method and a motion artifact reduction filter. Incorporating the Jacobian
      matrix in the regularization process, the new FER method with the motion artifact
      reduction filter offers stable reconstructions of high-fidelity images from noisy
      data by taking a very large regularization parameter value. The proposed method
      showed practical merits in experimental studies of chest EIT imaging.

PMID- 29035214
TI  - A Graph Cut Approach to Artery/Vein Classification in Ultra-Widefield Scanning
      Laser Ophthalmoscopy.
AB  - The classification of blood vessels into arterioles and venules is a fundamental
      step in the automatic investigation of retinal biomarkers for systemic diseases.
      In this paper, we present a novel technique for vessel classification on ultra
      wide-field-of-view images of the retinal fundus acquired with a scanning laser
      ophthalmoscope. To the best of our knowledge, this is the first time that a fully
      automated artery/vein classification technique for this type of retinal imaging
      with no manual intervention has been presented. The proposed method exploits hand
      crafted features based on local vessel intensity and vascular morphology to
      formulate a graph representation from which a globally optimal separation between
      the arterial and venular networks is computed by graph cut approach. The
      technique was tested on three different data sets (one publicly available and two
      local) and achieved an average classification accuracy of 0.883 in the largest
      data set.

PMID- 29035216
TI  - Spiral Flow Phantom for Ultrasound Flow Imaging Experimentation.
AB  - As new ultrasound flow imaging methods are being developed, there is a growing
      need to devise appropriate flow phantoms that can holistically assess the
      accuracy of the derived flow estimates. In this paper, we present a novel spiral
      flow phantom design whose Archimedean spiral lumen naturally gives rise to multi
      directional flow over all possible angles (i.e., from 0 degrees  to 360 degrees
      ). Developed using lost-core casting principles, the phantom geometry comprised a
      three-loop spiral (4-mm diameter and 5-mm pitch), and it was set to operate in
      steady flow mode (3 mL/s flow rate). After characterizing the flow pattern within
      the spiral vessel using computational fluid dynamics (CFD) simulations, the
      phantom was applied to evaluate the performance of color flow imaging (CFI) and
      high-frame-rate vector flow imaging. Significant spurious coloring artifacts were
      found when using CFI to visualize flow in the spiral phantom. In contrast, using
      vector flow imaging (least-squares multi-angle Doppler based on a three-transmit
      and three-receive configuration), we observed consistent depiction of flow
      velocity magnitude and direction within the spiral vessel lumen. The spiral flow
      phantom was also found to be a useful tool in facilitating demonstration of
      dynamic flow visualization based on vector projectile imaging. Overall, these
      results demonstrate the spiral flow phantom's practical value in analyzing the
      efficacy of ultrasound flow estimation methods.

PMID- 29035215
TI  - Task-Driven Optimization of Fluence Field and Regularization for Model-Based
      Iterative Reconstruction in Computed Tomography.
AB  - This paper presents a joint optimization of dynamic fluence field modulation
      (FFM) and regularization in quadratic penalized-likelihood reconstruction that
      maximizes a task-based imaging performance metric. We adopted a task-driven
      imaging framework for prospective designs of the imaging parameters. A maxi-min
      objective function was adopted to maximize the minimum detectability index ( )
      throughout the image. The optimization algorithm alternates between FFM
      (represented by low-dimensional basis functions) and local regularization
      (including the regularization strength and directional penalty weights). The task
      driven approach was compared with three FFM strategies commonly proposed for FBP
      reconstruction (as well as a task-driven TCM strategy) for a discrimination task
      in an abdomen phantom. The task-driven FFM assigned more fluence to less
      attenuating anteroposterior views and yielded approximately constant fluence
      behind the object. The optimal regularization was almost uniform throughout
      image. Furthermore, the task-driven FFM strategy redistribute fluence across
      detector elements in order to prescribe more fluence to the more attenuating
      central region of the phantom. Compared with all strategies, the task-driven FFM
      strategy not only improved minimum by at least 17.8%, but yielded higher over a
      large area inside the object. The optimal FFM was highly dependent on the amount
      of regularization, indicating the importance of a joint optimization. Sample
      reconstructions of simulated data generally support the performance estimates
      based on computed . The improvements in detectability show the potential of the
      task-driven imaging framework to improve imaging performance at a fixed dose, or,
      equivalently, to provide a similar level of performance at reduced dose.

PMID- 29035217
TI  - Oasis: Procedurally Generated Social Virtual Spaces from 3D Scanned Real Spaces.
AB  - We present Oasis, a novel system for automatically generating immersive and
      interactive virtual reality environments for single and multiuser experiences.
      Oasis enables real-walking in the generated virtual environment by capturing
      indoor scenes in 3D and mapping walkable areas. It makes use of available depth
      information for recognizing objects in the real environment which are paired with
      virtual counterparts to leverage the physicality of the real world, for a more
      immersive virtual experience. Oasis allows co-located and remotely located users
      to interact seamlessly and walk naturally in a shared virtual environment.
      Experiencing virtual reality with currently available devices can be cumbersome
      due to presence of objects and furniture which need to be removed every time the
      user wishes to use VR. Our approach is new, in that it allows casual users to
      easily create virtual reality environments in any indoor space without
      rearranging furniture or requiring specialized equipment, skill or training. We
      demonstrate our approach to overlay a virtual environment over an existing
      physical space through fully working single and multiuser systems implemented on
      a Tango tablet device.

PMID- 29035218
TI  - Interacting With Robots to Investigate the Bases of Social Interaction.
AB  - Humans show a great natural ability at interacting with each other. Such
      efficiency in joint actions depends on a synergy between planned collaboration
      and emergent coordination, a subconscious mechanism based on a tight link between
      action execution and perception. This link supports phenomena as mutual
      adaptation, synchronization, and anticipation, which cut drastically the delays
      in the interaction and the need of complex verbal instructions and result in the
      establishment of joint intentions, the backbone of social interaction. From a
      neurophysiological perspective, this is possible, because the same neural system
      supporting action execution is responsible of the understanding and the
      anticipation of the observed action of others. Defining which human motion
      features allow for such emergent coordination with another agent would be crucial
      to establish more natural and efficient interaction paradigms with artificial
      devices, ranging from assistive and rehabilitative technology to companion
      robots. However, investigating the behavioral and neural mechanisms supporting
      natural interaction poses substantial problems. In particular, the unconscious
      processes at the basis of emergent coordination (e.g., unintentional movements or
      gazing) are very difficult-if not impossible-to restrain or control in a
      quantitative way for a human agent. Moreover, during an interaction, participants
      influence each other continuously in a complex way, resulting in behaviors that
      go beyond experimental control. In this paper, we propose robotics technology as
      a potential solution to this methodological problem. Robots indeed can establish
      an interaction with a human partner, contingently reacting to his actions without
      losing the controllability of the experiment or the naturalness of the
      interactive scenario. A robot could represent an "interactive probe" to assess
      the sensory and motor mechanisms underlying human-human interaction. We discuss
      this proposal with examples from our research with the humanoid robot iCub,
      showing how an interactive humanoid robot could be a key tool to serve the
      investigation of the psychological and neuroscientific bases of social
      interaction.

PMID- 29035219
TI  - An Embedded Real-Time Processing Platform for Optogenetic Neuroprosthetic
      Applications.
AB  - Optogenetics offers a powerful new approach for controlling neural circuits. It
      has numerous applications in both basic and clinical science. These applications
      require stimulating devices with small processors that can perform real-time
      neural signal processing, deliver high-intensity light with high spatial and
      temporal resolution, and do not consume a lot of power. In this paper, we
      demonstrate the implementation of neuronal models in a platform consisting of an
      embedded system module and a portable digital light processing projector. As a
      replacement for damaged neural circuitry, the embedded module processes neural
      signals and then directs the projector to optogenetically activate a downstream
      neural pathway. We present a design in the context of stimulating circuits in the
      visual system, but the approach is feasible for a broad range of biomedical
      applications.

PMID- 29035221
TI  - Spiking Neural P Systems With Scheduled Synapses.
AB  - Spiking neural P systems (SN P systems) are models of computation inspired by
      biological spiking neurons. SN P systems have neurons as spike processors, which
      are placed on the nodes of a directed and static graph (the edges in the graph
      are the synapses). In this paper, we introduce a variant called SN P systems with
      scheduled synapses (SSN P systems). SSN P systems are inspired and motivated by
      the structural dynamism of biological synapses, while incorporating ideas from
      nonstatic (i.e., dynamic) graphs and networks. In particular, synapses in SSN P
      systems are available only at specific durations according to their schedules.
      The SSN P systems model is a response to the problem of introducing durations to
      synapses of SN P systems. Since SN P systems are in essence static graphs, it is
      natural to consider them for dynamic graphs also. We introduce local and global
      schedule types, also taking inspiration from the above-mentioned sources. We
      prove that SSN P systems are computationally universal as number generators and
      acceptors for both schedule types, under a normal form (i.e., a simplifying set
      of restrictions). The introduction of synapse schedules for either schedule type
      proves useful in programming the system, despite restrictions in the normal form.

PMID- 29035220
TI  - Robot Training With Vector Fields Based on Stroke Survivors' Individual Movement
      Statistics.
AB  - The wide variation in upper extremity motor impairments among stroke survivors
      necessitates more intelligent methods of customized therapy. However, current
      strategies for characterizing individual motor impairments are limited by the use
      of traditional clinical assessments (e.g., Fugl-Meyer) and simple engineering
      metrics (e.g., goal-directed performance). Our overall approach is to
      statistically identify the range of volitional movement capabilities, and then
      apply a robot-applied force vector field intervention that encourages under
      expressed movements. We investigated whether explorative training with such
      customized force fields would improve stroke survivors' (n = 11) movement
      patterns in comparison to a control group that trained without forces (n = 11).
      Force and control groups increased Fugl-Meyer UE scores (average of 1.0 and 1.1,
      respectively), which is not considered clinically meaningful. Interestingly,
      participants from both groups demonstrated dramatic increases in their range of
      velocity during exploration following only six days of training (average increase
      of 166.4% and 153.7% for the Force and Control group, respectively). While both
      groups showed evidence of improvement, we also found evidence that customized
      forces affected learning in a systematic way. When customized forces were active,
      we observed broader distributions of velocity that were not present in the
      controls. Second, we found that these changes led to specific changes in
      unassisted motion. In addition, while the shape of movement distributions changed
      significantly for both groups, detailed analysis of the velocity distributions
      revealed that customized forces promoted a greater proportion of favorable
      changes. Taken together, these results provide encouraging evidence that patient
      specific force fields based on individuals' movement statistics can be used to
      create new movement patterns and shape them in a customized manner. To the best
      of our knowledge, this paper is the first to directly link engineering
      assessments of stroke survivors' exploration movement behaviors to the design of
      customized robot therapy.

PMID- 29035222
TI  - An Advanced MRI Multi-Modalities Segmentation Methodology Dedicated to Multiple
      Sclerosis Lesions Exploration and Differentiation.
AB  - Multiple sclerosis (MS) is one of the most common neurological diseases in young
      people. This paper dealt with an automatic biomedical aided tool involving
      volumetric segmentation of multiple sclerosis lesions. To meet this challenge,
      our proposed methodology requires one preliminary cerebral zones segmentation
      performed using a new Gaussian mixture model based on various databases atlases.
      Afterward, lesion segmentation begins with the estimation of a lesion map, which
      is then subjected to threshold constraints and refined by a new lesion expansion
      algorithm. The evaluation was carried out on four clinical databases integrating
      various clinical cases which had different lesion loads and were presented by a
      set of MRI modalities at several noise levels. The results compared with those of
      the existing methods proved excellent cerebral segmentation with dice averages
      close to 0.8 and sensitivity and specificity averages greater than 0.9. In
      addition, depending on the used database, the lesion segmentation recorded mean
      values were close to or greater than 0.8 for the different metrics. The detection
      error and outline error averages were about 0.3. Besides the ability to identify
      the lesions affecting the different parts of the brain, even those spreading in
      the gray matter, the proposed methodology identified the lesions cores and their
      surrounding vasogenic edema. This has been thoroughly tested and validated by
      highly qualified radiologists and neurologists. The evaluation of the resulting
      discriminations recorded values close to or greater than 0.9 for dice,
      sensitivity, and specificity. As a valuable benefit, a computer aided diagnosis
      tool could be offered to clinicians. It would help efficiently during the MS
      diagnosis and avoid several confusions. Besides, it could be used for
      longitudinal survey and henceforth extends to other pathologies that could be
      explored by MRI modalities, such as glioblastoma or alzheimer's disease.

PMID- 29035223
TI  - fmpRPMF: A Web Implementation for Protein Identification by Robust Peptide Mass
      Fingerprinting.
AB  - Peptide mass fingerprinting continues to play an important role in current
      proteomics studies based on its good performance in sample throughput,
      specificity for single peptides, and insensitive to unexpected post-translational
      modifications as compared with . Here, we proposed and evaluated the use of
      feature-matching pattern-based support vector machines (SVMs) for robust protein
      identification. This approach is now facilitated with an updated web server
      (fmpRPMF) incorporated with several newly developed or improved modules and
      workflows allowing identification of proteins from data.

PMID- 29035224
TI  - Efficient Local Search for Euclidean Path-Difference Median Trees.
AB  - Synthesizing large-scale phylogenetic trees is a fundamental problem in
      evolutionary biology. Median tree problems have evolved as a powerful tool to
      reconstruct such trees. Such problems seek a median tree for a given collection
      of input trees under some problem-specific tree distance. There has been an
      increased interest in the median tree problem for the classical path-difference
      distance between trees. While this problem is NP-hard, standard local search
      heuristics have been described that are based on solving a local search problem
      exactly. For a more effective heuristic we devise a time efficient algorithm for
      the local search problem that improves on the best-known solution by a factor of
      n, where n is the size of the input trees. Furthermore, we introduce a novel
      hybrid version of the standard local search that is exploiting our new algorithm
      for a more refined heuristic search. Finally, we demonstrate the performance of
      our hybrid heuristic in a comparative study with other commonly used methods that
      synthesize species trees using published empirical data sets.

PMID- 29035227
TI  - Bayesian Nonparametric Regression Modeling of Panel Data for Sequential
      Classification.
AB  - This paper proposes a Bayesian nonparametric regression model of panel data for
      sequential pattern classification. The proposed method provides a flexible and
      parsimonious model that allows both time-independent spatial variables and time
      dependent exogenous variables to be predictors. Not only this method improves the
      accuracy of parameter estimation for limited data, but also it facilitates model
      interpretation by identifying statistically significant predictors with
      hypothesis testing. Moreover, as the data length approaches infinity, posterior
      consistency of the model is guaranteed for general data-generating processes
      under regular conditions. The resulting model of panel data can also be used for
      sequential classification. The proposed method has been tested by numerical
      simulation, then validated on an econometric public data set, and subsequently
      validated for detection of combustion instabilities with experimental data that
      have been generated in a laboratory environment.

PMID- 29035225
TI  - A Review of Automated Methods for Detection of Myocardial Ischemia and Infarction
      Using Electrocardiogram and Electronic Health Records.
AB  - There is a growing body of research focusing on automatic detection of ischemia
      and myocardial infarction (MI) using computer algorithms. In clinical settings,
      ischemia and MI are diagnosed using electrocardiogram (ECG) recordings as well as
      medical context including patient symptoms, medical history, and risk factors
      information that is often stored in the electronic health records. The ECG signal
      is inspected to identify changes in the morphology such as ST-segment deviation
      and T-wave changes. Some of the proposed methods compute similar features
      automatically while others use nonconventional features such as wavelet
      coefficients. This review provides an overview of the methods that have been
      proposed in this area, focusing on their historical evolution, the publicly
      available datasets that they have used to evaluate their performance, and the
      details of their algorithms for ECG and EHR analysis. The validation strategies
      that have been used to evaluate the performance of the proposed methods are also
      presented. Finally, the paper provides recommendations for future research to
      address the shortcomings of the currently existing methods and practical
      considerations to make the proposed technical solutions applicable in clinical
      practice.

PMID- 29035226
TI  - Evaluating Approaches to Rendering Braille Text on a High-Density Pin Display.
AB  - Refreshable displays for tactile graphics are typically composed of pins that
      have smaller diameters and spacing than standard braille dots. We investigated
      configurations of high-density pins to form braille text on such displays using
      non-refreshable stimuli produced with a 3D printer. Normal dot braille (diameter
      1.5 mm) was compared to high-density dot braille (diameter 0.75 mm) wherein each
      normal dot was rendered by high-density simulated pins alone or in a cluster of
      pins configured in a diamond, X, or square; and to "blobs" that could result from
      covering normal braille and high-density multi-pin configurations with a thin
      membrane. Twelve blind participants read MNREAD sentences displayed in these
      conditions. For high-density simulated pins, single pins were as quickly and
      easily read as normal braille, but diamond, X, and square multi-pin
      configurations were slower and/or harder to read than normal braille. We
      therefore conclude that as long as center-to-center dot spacing and dot placement
      is maintained, the dot diameter may be open to variability for rendering braille
      on a high density tactile display.

PMID- 29035228
TI  - Universal Approximation by Using the Correntropy Objective Function.
AB  - Several objective functions have been proposed in the literature to adjust the
      input parameters of a node in constructive networks. Furthermore, many
      researchers have focused on the universal approximation capability of the network
      based on the existing objective functions. In this brief, we use a correntropy
      measure based on the sigmoid kernel in the objective function to adjust the input
      parameters of a newly added node in a cascade network. The proposed network is
      shown to be capable of approximating any continuous nonlinear mapping with
      probability one in a compact input sample space. Thus, the convergence is
      guaranteed. The performance of our method was compared with that of eight
      different objective functions, as well as with an existing one hidden layer
      feedforward network on several real regression data sets with and without
      impulsive noise. The experimental results indicate the benefits of using a
      correntropy measure in reducing the root mean square error and increasing the
      robustness to noise.

PMID- 29035229
TI  - Transductive Zero-Shot Learning With Adaptive Structural Embedding.
AB  - Zero-shot learning (ZSL) endows the computer vision system with the inferential
      capability to recognize new categories that have never seen before. Two
      fundamental challenges in it are visual-semantic embedding and domain adaptation
      in cross-modality learning and unseen class prediction steps, respectively. This
      paper presents two corresponding methods named Adaptive STructural Embedding
      (ASTE) and Self-PAced Selective Strategy (SPASS) for both challenges.
      Specifically, ASTE formulates the visual-semantic interactions in a latent
      structural support vector machine framework by adaptively adjusting the slack
      variables to embody different reliablenesses among training instances. To
      alleviate the domain shift problem in ZSL, SPASS borrows the idea from self-paced
      learning by iteratively selecting the unseen instances from reliable to less
      reliable to gradually adapt the knowledge from the seen domain to the unseen
      domain. Consequently, by combining SPASS and ASTE, we present a self-paced
      Transductive ASTE (TASTE) method to progressively reinforce the classification
      capacity. Extensive experiments on three benchmark data sets (i.e., AwA, CUB, and
      aPY) demonstrate the superiorities of ASTE and TASTE. Furthermore, we also
      propose a fast training (FT) strategy to improve the efficiency of most existing
      ZSL methods. The FT strategy is surprisingly simple and general enough, which
      speeds up the training time of most existing ZSL methods by 4~300 times while
      holding the previous performance.

PMID- 29035230
TI  - A Deep Machine Learning Method for Classifying Cyclic Time Series of Biological
      Signals Using Time-Growing Neural Network.
AB  - This paper presents a novel method for learning the cyclic contents of stochastic
      time series: the deep time-growing neural network (DTGNN). The DTGNN combines
      supervised and unsupervised methods in different levels of learning for an
      enhanced performance. It is employed by a multiscale learning structure to
      classify cyclic time series (CTS), in which the dynamic contents of the time
      series are preserved in an efficient manner. This paper suggests a systematic
      procedure for finding the design parameter of the classification method for a one
      versus-multiple class application. A novel validation method is also suggested
      for evaluating the structural risk, both in a quantitative and a qualitative
      manner. The effect of the DTGNN on the performance of the classifier is
      statistically validated through the repeated random subsampling using different
      sets of CTS, from different medical applications. The validation involves four
      medical databases, comprised of 108 recordings of the electroencephalogram
      signal, 90 recordings of the electromyogram signal, 130 recordings of the heart
      sound signal, and 50 recordings of the respiratory sound signal. Results of the
      statistical validations show that the DTGNN significantly improves the
      performance of the classification and also exhibits an optimal structural risk.

PMID- 29035231
TI  - On Adaptive Boosting for System Identification.
AB  - In the field of machine learning, the algorithm Adaptive Boosting has been
      successfully applied to a wide range of regression and classification problems.
      However, to the best of the authors' knowledge, the use of this algorithm to
      estimate dynamical systems has not been exploited. In this brief, we explore the
      connection between Adaptive Boosting and system identification, and give examples
      of an identification method that makes use of this connection. We prove that the
      resulting estimate converges to the true underlying system for an output-error
      model structure under reasonable assumptions in the large sample limit and derive
      a bound of the model mismatch for the noise-free case.

PMID- 29035232
TI  - Stability Analysis of Optimal Adaptive Control Under Value Iteration Using a
      Stabilizing Initial Policy.
AB  - Adaptive optimal control using value iteration initiated from a stabilizing
      control policy is theoretically analyzed. The analysis is in terms of stability
      of the system during the learning stage and includes the system controlled by any
      fixed control policy and also by an evolving policy. A feature of the presented
      results is finding subsets of the region of attraction. This is done so that if
      the initial condition belongs to this region, the entire state trajectory remains
      within the training region. Therefore, the function approximation results remain
      reliable, as no extrapolation will be conducted.

PMID- 29035233
TI  - GII Representation-Based Cross-View Gait Recognition by Discriminative Projection
      With List-Wise Constraints.
AB  - Remote person identification by gait is one of the most important topics in the
      field of computer vision and pattern recognition. However, gait recognition
      suffers severely from the appearance variance caused by the view change. It is
      very common that gait recognition has a high performance when the view is fixed
      but the performance will have a sharp decrease when the view variance becomes
      significant. Existing approaches have tried all kinds of strategies like tensor
      analysis or view transform models to slow down the trend of performance decrease
      but still have potential for further improvement. In this paper, a discriminative
      projection with list-wise constraints (DPLC) is proposed to deal with view
      variance in cross-view gait recognition, which has been further refined by
      introducing a rectification term to automatically capture the principal
      discriminative information. The DPLC with rectification (DPLCR) embeds list-wise
      relative similarity measurement among intraclass and inner-class individuals,
      which can learn a more discriminative and robust projection. Based on the
      original DPLCR, we have introduced the kernel trick to exploit nonlinear cross
      view correlations and extended DPLCR to deal with the problem of multiview gait
      recognition. Moreover, a simple yet efficient gait representation, namely gait
      individuality image (GII), based on gait energy image is proposed, which could
      better capture the discriminative information for cross view gait recognition.
      Experiments have been conducted in the CASIA-B database and the experimental
      results demonstrate the outstanding performance of both the DPLCR framework and
      the new GII representation. It is shown that the DPLCR-based cross-view gait
      recognition has outperformed the-state-of-the-art approaches in almost all cases
      under large view variance. The combination of the GII representation and the
      DPLCR has further enhanced the performance to be a new benchmark for cross-view
      gait recognition.

PMID- 29035234
TI  - A Generalized Methodology for Data Analysis.
AB  - Based on a critical analysis of data analytics and its foundations, we propose a
      functional approach to estimate data ensemble properties, which is based entirely
      on the empirical observations of discrete data samples and the relative proximity
      of these points in the data space and hence named empirical data analysis (EDA).
      The ensemble functions include the nonparametric square centrality (a measure of
      closeness used in graph theory) and typicality (an empirically derived quantity
      which resembles probability). A distinctive feature of the proposed new
      functional approach to data analysis is that it does not assume randomness or
      determinism of the empirically observed data, nor independence. The typicality is
      derived from the discrete data directly in contrast to the traditional approach,
      where a continuous probability density function is assumed a priori. The
      typicality is expressed in a closed analytical form that can be calculated
      recursively and, thus, is computationally very efficient. The proposed
      nonparametric estimators of the ensemble properties of the data can also be
      interpreted as a discrete form of the information potential (known from the
      information theoretic learning theory as well as the Parzen windows). Therefore,
      EDA is very suitable for the current move to a data-rich environment, where the
      understanding of the underlying phenomena behind the available vast amounts of
      data is often not clear. We also present an extension of EDA for inference. The
      areas of applications of the new methodology of the EDA are wide because it
      concerns the very foundation of data analysis. Preliminary tests show its good
      performance in comparison to traditional techniques.

PMID- 29035235
TI  - Asymmetric Game: A Silver Bullet to Weighted Vertex Cover of Networks.
AB  - Weighted vertex cover (WVC), a generalized type of vertex cover, is one of the
      most important combinatorial optimization problems. In this paper, we provide a
      novel solution to the WVC problem from the view of network engineering. We model
      the WVC problem as an asymmetric game on weighted networks, where each vertex is
      treated as an intelligent rational agent rather than an inanimate one. Under the
      framework of asymmetric game, we find that strict Nash equilibriums of the
      asymmetric game are the intermediate states between the WVC states and the
      minimum WVC (MWVC) states. Besides, we propose best response algorithms with
      memory and feedback to solve the WVC problem, and find that a better approximate
      solution to the MWVC can be obtained under the feedback-based best response
      algorithm. Numerical illustrations verify the performance of the proposed game
      solution on weighted networks. Our findings pave a new way to solve the WVC
      problem from the perspective of asymmetric game, which opens a bottom-up avenue
      to address the combinatorial optimization problems.

PMID- 29035236
TI  - Fuzzy Adaptive Compensation Control of Uncertain Stochastic Nonlinear Systems
      With Actuator Failures and Input Hysteresis.
AB  - Hysteresis exists ubiquitously in physical actuators. Besides, actuator
      failures/faults may also occur in practice. Both effects would deteriorate the
      transient tracking performance, and even trigger instability. In this paper, we
      consider the problem of compensating for actuator failures and input hysteresis
      by proposing a fuzzy control scheme for stochastic nonlinear systems. Compared
      with the existing research on stochastic nonlinear uncertain systems, it is found
      that how to guarantee a prescribed transient tracking performance when taking
      into account actuator failures and hysteresis simultaneously also remains to be
      answered. Our proposed control scheme is designed on the basis of the fuzzy logic
      system and backstepping techniques for this purpose. It is proven that all the
      signals remain bounded and the tracking error is ensured to be within a
      preestablished bound with the failures of hysteretic actuator. Finally,
      simulations are provided to illustrate the effectiveness of the obtained
      theoretical results.

PMID- 29035237
TI  - Robust Adaptive Fuzzy Control of a Class of Uncertain Nonlinear Systems With
      Unstable Dynamics and Mismatched Disturbances.
AB  - This paper studies the robust stabilization problem for a class of uncertain
      nonlinear systems with unstable zero dynamics. The considered zero dynamic is not
      assumed to be input-to-state practically stable and contains nonlinear
      uncertainties and mismatched external disturbances. A new robust adaptive fuzzy
      control method is developed by combining theory with backstepping technique.
      First, an ideal virtual control function is designed, which can guarantee the
      zero dynamic asymptotically stable with a suboptimal performance. Then, based on
      some non-negative functions and backstepping design, the actual controller is
      constructed for the overall system, which ensures that the tracking error for the
      ideal virtual control signal converges to a priori accuracy regardless of
      external disturbances. In this design, an auxiliary signal is introduced to
      overcome the difficulties from the unavailable virtual reference signal. By
      exploiting the implicit function theorem, the proposed design technique is
      directly applied to a special case, where the zero dynamic is partially linear. A
      two inverted pendulums is used to illustrate the application and effectiveness of
      the proposed design method.

PMID- 29035238
TI  - Neuroadaptive Control of Strict Feedback Systems With Full-State Constraints and
      Unknown Actuation Characteristics: An Inexpensive Solution.
AB  - In this paper, we present a neuroadaptive control for a class of uncertain
      nonlinear strict-feedback systems with full-state constraints and unknown
      actuation characteristics where the break points of the dead-zone model are
      considered as time-variant. In order to deal with the modeling uncertainties and
      the impact of the nonsmooth actuation characteristics, neural networks are
      utilized at each step of the backstepping design. By using barrier Lyapunov
      function, together with the concept of virtual parameter, we develop a
      neuroadaptive control scheme ensuring tracking stability and at the same time
      maintaining full-state constraints. The proposed control strategy bears the
      structure of proportional-integral (PI) control, with the PI gains being
      automatically and adaptively determined, making its design less demanding and its
      implementation less costly. Both theoretical analysis and numerical simulation
      validate the benefits and the effectiveness of the proposed method.

PMID- 29035239
TI  - Diagnosis of Trichomoniasis in Male Patients on Performing Nested Polymerase
      Chain Reaction.
AB  - OBJECTIVE: Trichomoniasis is a parasitic infection that occurs with the
      settlement of Trichomonas vaginalis in female and male urinary and reproductive
      tracts. This infection is generally asymptomatic in males, and males are thought
      to be a carrier for the transmission of infection. In this study, our aim was to
      detect trichomoniasis using nested polymerase chain reaction among males who were
      referred to a hospital with suspected urinary tract infection. METHODS: Urine
      samples were collected from 138 male patients between 18 and 50 years of age who
      were referred with suspected urinary system infection to the Urology Outpatient
      Clinic at Malatya University Medical Center Malatya between December 2013 and May
      2014. Direct microscopy, two different culture methods, and nested Polymerase
      chain reaction (PCR) were performed for the investigation of T. vaginalis in
      urine samples. RESULTS: Urinary tract infection was diagnosed in 47 of the 138
      patients according to white and red blood cell counts in the urine samples. T.
      vaginalis infection was detected in 6.5% (9/138) of the suspected patients by
      nested PCR, while none of the samples tested positive by direct microscopy and
      culture examinations. Statistical significance was found between infection of the
      urinary tract and nested PCR positivity for T. vaginalis. CONCLUSIONS: According
      to our results, nested PCR is the most sensitive method for the detection of
      trichomoniasis in male patients. We strongly recommend using nested PCR for the
      differential diagnosis of urinary infections in males.

PMID- 29035240
TI  - Seroprevalence of Neospora caninum in Dairy Cattle Raised in Cicekdagi District
      of Kirsehir Province.
AB  - OBJECTIVE: Neospora caninum is one of the most important causes of abortion in
      cattle worldwide and causes significant economic losses in the meat and dairy
      industries. This study aimed to determine the seroprevalence of N. caninum in
      dairy cattle raised in Cicekdagi district of Kirsehir province. METHODS: One
      hundred sixteen serum samples collected from dairy cattle were analyzed for N.
      caninum antibodies by a commercial Enzyme-Linked ImmunoSorbent Assay (ELISA) kit
      (VMRD c-ELISA). RESULTS: The seropositivity rate was 18.1% in the cattle
      examined. The seroprevalence of N. caninum was 23.4% in dairy cattle with
      fertility problems, 33.3% in cattle with a history of abortion, and 7.8% in
      clinically healthy dairy cattle (p=0.006). Cattle breeds with highest
      seropositivity rates were Holstein, Simmental, and Brown Swiss (p=0.008).
      CONCLUSION: Control measures should be taken for both dogs as final host of the
      parasite cattle to prevent the spread of neosporosis in cattle in Cicekdagi
      district.

PMID- 29035241
TI  - Eustigmaeus johnstoni Zhang - Gerson (Acari: Stigmaeidae) a Parasitic Mite
      Species Detected in Phlebotomus papatasi (Diptera: Psychodidae) Specimens
      Collected from Aydin, Turkey.
AB  - OBJECTIVE: We aimed to report the presence of the parasitic mite Eustigmaeus
      johnstoni Zhang - Gerson (E. johnstoni) on the sand fly species Phlebotomus
      papatasi (P. papatasi) collected in Aydin province, Turkey. METHODS: Sand flies
      were collected from nature by CDC light traps in Nazilli town in Aydin province
      and were separated according to collection localities. Head and genital areas
      were cut and mounted for species identification, and midgut contents were checked
      for the possible presence of Leishmania parasites under a light microscope. Mites
      detected in sand flies were diagnosed on the species level based on the
      literature. RESULTS: A total of 360 female and 378 male sand flies were caught.
      During dissection and preparation, two female E. johnstoni parasitic mite
      specimens belonging to the genus Eustigmaeus were detected on the abdominal
      pleura of P. papatasi specimens. CONCLUSION: To our knowledge, this is the first
      study to report the presence E. johnstoni on P. papatasi in Turkey. Previous
      studies showing the relationship between parasitic mites and sand flies have
      indicated that this relationship is not accidental. More studies are needed to
      understand this relationship for obtaining more detailed information.

PMID- 29035242
TI  - The Effect of Skin Sebum, pH, and Moisture on Demodex Infestation in Acne
      Vulgaris and Rosacea Patients.
AB  - OBJECTIVE: Acne vulgaris is an inflammatory disease involving the pilosebaceous
      unit. Rosacea is a chronic inflammatory skin disease that affects the face in
      particular. This study aimed to determine if skin sebum, pH, and moisture affect
      the number of Demodex spp. in acne vulgaris and rosacea patients. METHODS: This
      study focused on 30 patients each with acne vulgaris and rosacea. As a control
      group, 60 healthy individuals were included. RESULTS: In acne vulgaris patients,
      when compared to those with Demodex mite more than 5 /cm2 in each area, less than
      5/cm2 were found to be oily, acidic, dry or very dry. However, there was no
      significant difference in moisture value. In patients with rosacea, the skin was
      acidic and dry in patients those with more than 5/cm2 Demodex mites when compared
      to those with demodex mite less than 5 /cm2 in patients in each of the right
      cheek and nose areas. There was no difference in skin oil level. CONCLUSION: The
      oily, acidic, dry, and very dry skin of the acne vulgaris patients and the oily,
      acidic, and very dry skin of the rosacea patients are factors facilitating the
      development of Demodex ssp.

PMID- 29035243
TI  - Seroprevalence of Toxoplasma gondii in Sheep from Nevsehir Province inTurkey.
AB  - OBJECTIVE: The goal of this study was to investigate the seroprevalence of
      Toxoplasma gondii (T. gondii) in sheep from Nevsehir Province in Turkey. METHODS:
      Blood samples were taken from 180 sheep aged between 1 and 7 years, which were
      randomly selected from seven different study sites in Nevsehir Province. The
      enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to T.
      gondii was performed on all the serum samples. RESULTS: Eighteen (10%) serum
      samples were found to be seropositive for T. gondii antibodies. The highest
      seropositivity rate (11.53%) was found in sheep aged between 1 and 2 years,
      whereas the lowest seropositivity rate (8.51%) was found in sheep aged between 5
      and 7 years old. Eighteen of the 162 ewes (11.1%) were found to be seropositive,
      whereas none of the 18 tested rams were seropositive. In addition, considering
      the study site location, the highest seropositivity rate was in Avanos (32%),
      whereas the lowest seropositivity rate was in Kozakli (2.9%). The T. gondii
      seropositivity rates were statistically insignificant with regard to age groups
      and gender (p>0.05), whereas they were statistically significant (p<0.05) with
      regard to study centers. CONCLUSION: This is the first serological report on
      toxoplasmosis in sheep from Nevsehir Province in Turkey.

PMID- 29035244
TI  - Cryopreservation of Leishmania Species in Manisa Province.
AB  - OBJECTIVE: It was aimed to assess the success of the cryopreservation process
      which is carried out in order to preserve the genetic material and the virulence
      of the Leishmania species that are an important health problem in our region.
      METHODS: Leishmania tropica, L. infantum, L. major, and L. donovani strains in
      Novy-MacNeal-Nicolle (NNN) medium in MCBU were used. Promastigotes cultured in
      the NNN medium were transferred to RPMI 1640 medium; promastigotes in the
      logarithmic phase were washed three times with PBS, and 15% dimethylsulfoxide
      (DMSO) was added. Leishmania species were transferred to 12 separate tubes. The
      tubes were stored at -86 degrees C for one night by placing them in Coolcell
      boxes. The tubes were transferred into a liquid nitrogen tank. One cryotube per
      Leishmania strain is thawed monthly and cultured in NNN medium. RESULTS: For the
      duration of study it was observed that each Leishmania isolate preserved 60-65%
      of their viability and entered the logarithmic phase on the 7th day following the
      inoculation in the NNN medium. Abnormalities in the structures and movements of
      the promastigotes were not observed in microscopic examinations. CONCLUSION: The
      following conclusions were made: cryopreservation is important for studies
      planned related to leishmaniasis and cryopreservation with DMSO is successful.

PMID- 29035245
TI  - In vivo and in vitro Models for Scanning Drug Substances in Malaria: Prestudy.
AB  - OBJECTIVE: The Wolrd Health Organization (WHO) encourages all countries to
      investigate antimalarial drug substances derived from herbal sources with the
      slogan "Hunt of the Next Artemisinin" due to the emergence of resistant strains
      of Plasmodium species to artemisinin. In the broad and simple sense, it was
      planned to help guide the young researchers set in-vitro and in-vivo models of
      malaria in order to be used in drug research and active ingredient studies.
      METHODS: In-vitro study, young Plasmodium berghei trophozoites were removed from
      the liquid nitrogen tank and resuspended in appropriate conditions, followed by
      incubation with chloroquine and tetracycline at concentrations of 0.1, 0.4, 0.8,
      1.6, 6.4, 12.8 MUg/mL for 24 hours at +37 degrees C in a shaking incubator. In
      vivo studies, Tetracycline group (TG) and Chloroquine group (KG) were
      administered 50 mg/kg of tetracycline and chloroquine by intragastric lavage and
      untreated control group (TACG) were administered the same amount of saline via
      the same route. The suppression of parasitemia in mice was followed for 24 days.
      RESULTS: In our in-vitro study it was observed that 0.8 MUg/mL of chloroquine and
      1.6 MUg/mL of tetracycline was enough to suppress parasitemia. In our in-vivo
      drug study, all of the mice in the TG group died at day 24, and all of the mice
      in the TAKG group died at day 12, with no parasitemia observed in the mice in the
      KG group. CONCLUSION: Our study suggests that if tetracycline therapy is
      administered when the induction of chloroquine therapy is delayed, the
      exacerbation of the parasitemia may be prevented and when chloroquine is obtained
      chloroquine therapy can be commenced thus preventing the loss of the patient.

PMID- 29035246
TI  - Effect of Extracts of the Endemic Plants Centaurea lydia and Phlomis nissolii on
      Toxoplasma gondii.
AB  - OBJECTIVE: This study aimed to investigate the potential antitoxoplasma
      activities of extracts of the endemic plants Centaurea lydia and Phlomis nissolii
      in a fibroblast cell culture infected with T. gondii trophozoites. METHODS: WI-38
      cell lines treated with plant extracts (55 MUg/mL each) and an untreated control
      were infected with 5*105 T. gondii trophozoites, and the number of parasites in
      the medium was determined on days 7, 14, and 24. RESULTS: No cytotoxic effects of
      C. lydia and P. nissolii extracts were detected at concentrations of 0.86-55
      MUg/mL in the WI-38 cell line, and the absence of the cytotoxicity of these
      extracts on the fibroblast cell line was considered as a positive effect. C.
      lydia extract at 55 MUg/mL had marked activity against T. gondii trophozoites. A
      47.5-fold increase was observed in the number of trophozoites in the control
      group, while a 84-fold decrease was found in the C. lydia extract group. However,
      a 36-fold increase was detected in the P. nissolii extract group, indicating no
      antitoxoplasma activity. CONCLUSION: The extract of C. lydia, an endemic plant,
      was found to be a good drug candidate for treating toxoplasmosis. The in vitro
      activity of the extract of this endemic plant should be further investigated in
      animal models in vivo.

PMID- 29035247
TI  - Importance of Land Snails in Dicrocoeliosis Epidemiology.
AB  - Dicrocoeliosis is a helminthosis caused by the small liver fluke Dicrocoelium
      spp. (Trematoda, Dicrocoeliidae) parasitizing in the bile ducts and gall bladder
      of ruminants as well as many other animal species including humans. In the
      biological life cycle of Dicrocoelium, land snails are first intermediate hosts
      and ants are second intermediate hosts. Sporocysts and cercaria, which are larval
      stages, live in the hepatopancreas of land snails and metacercaria, which is also
      the larval stage, lives in the abdomen and brain of ants. Land snails, which are
      the first intermediate host of this parasite in Turkey, include Helicopsis
      derbentina, Helicopsis protea, Helicopsis krynickii, Cernuella virgata,
      Trochoidea pyramidata, Cochicella acuta, Monacha carthusiana, Helicella
      candicans, Helix aspersa, Helix lucorum, and Chondrus tournefortianus.
      Dicrocoeliosis is widespread in ruminants and affects their liver, which can lead
      to weight loss and reduced milk production. The number of reports on
      dicrocoeliosis is increasing due to the expansion of dry habitats and parasites
      becoming resistant to antihelminthic drugs. This study provides information on
      the epidemiology and control methods of Dicrocoelium.

PMID- 29035248
TI  - Furuncular Myiasis Caused by Dermatobia hominis in a Traveler Returning from the
      Amazon Jungle.
AB  - A 39-year-old man who was returning from the Amazon Jungle and had no medical
      history presented with a furuncular lesion on his right parietal scalp. Despite
      receiving appropriate antimicrobial treatment, his lesion did not heal. After
      surgical intervention, a Dermatobia hominis larva was extracted. The human botfly
      D. hominis is the most common causative agent of furuncular myiasis among
      travelers returning from Central and South America. Surgery is the main treatment
      option, and secondary bacterial infection should be kept in mind.

PMID- 29035249
TI  - Chronic Hepatitis B and Leishmania Coinfection.
AB  - Visceral leishmaniasis is an endemic disease in many parts of world, and if
      untreated, it is a potentially life-threatening infectious disease. It is similar
      to chronic liver disease because of signs and symptoms such as fever, weight
      loss, hepatosplenomegaly, and pancytopenia. In this study, we present a case of
      visceral leishmaniasis, which is known to be a chronic hepatitis B infection,
      that was coincidentally diagnosed with liver biopsy. Visceral leishmaniasis
      should be considered as an infectious disease in the differential diagnosis of
      chronic liver diseases.

PMID- 29035250
TI  - Rare But Life-Threatening Complication of Hydatid Disease.
AB  - Cystic echinococcosis is an infectious disease that is potentially associated
      with the biliary tract. Of thousand cases of hydatid cysts that were successfully
      treated by the Ormeci method, only two presented with cholangitis subsequent to
      the percutaneous treatment. These cases were treated with endoscopic retrograde
      cholangiopancreatography, and this study provides details regarding the clear
      fistulization of hydatid cysts into the biliary tract.

PMID- 29035252
TI  - Atmospheric transport of trace elements and nutrients to the oceans.
AB  - This paper reviews atmospheric inputs of trace elements and nutrients to the
      oceans in the context of the GEOTRACES programme and provides new data from two
      Atlantic GEOTRACES cruises. We consider the deposition of nitrogen to the oceans,
      which is now dominated by anthropogenic emissions, the deposition of mineral dust
      and related trace elements, and the deposition of other trace elements which have
      a mixture of anthropogenic and dust sources. We then consider the solubility (as
      a surrogate for bioavailability) of the various elements. We consider briefly the
      sources, atmospheric transport and transformations of these elements and how this
      results in strong spatial deposition gradients. Solubility of the trace elements
      also varies systematically between elements, reflecting their sources and
      cycling, and for some trace elements there are also systematic gradients in
      solubility related to dust loading. Together, these effects create strong spatial
      gradients in the inputs of bioavailable trace elements to the oceans, and we are
      only just beginning to understand how these affect ocean biogeochemistry.This
      article is part of the themed issue 'Biological and climatic impacts of ocean
      trace element chemistry'.

PMID- 29035251
TI  - How well can we quantify dust deposition to the ocean?
AB  - Deposition of continental mineral aerosols (dust) in the Eastern Tropical North
      Atlantic Ocean, between the coast of Africa and the Mid-Atlantic Ridge, was
      estimated using several strategies based on the measurement of aerosols, trace
      metals dissolved in seawater, particulate material filtered from the water
      column, particles collected by sediment traps and sediments. Most of the data
      used in this synthesis involve samples collected during US GEOTRACES expeditions
      in 2010 and 2011, although some results from the literature are also used. Dust
      deposition generated by a global model serves as a reference against which the
      results from each observational strategy are compared. Observation-based dust
      fluxes disagree with one another by as much as two orders of magnitude, although
      most of the methods produce results that are consistent with the reference model
      to within a factor of 5. The large range of estimates indicates that further work
      is needed to reduce uncertainties associated with each method before it can be
      applied routinely to map dust deposition to the ocean. Calculated dust deposition
      using observational strategies thought to have the smallest uncertainties is
      lower than the reference model by a factor of 2-5, suggesting that the model may
      overestimate dust deposition in our study area.This article is part of the themed
      issue 'Biological and climatic impacts of ocean trace element chemistry'.

PMID- 29035253
TI  - Overview of the mechanisms that could explain the 'Boundary Exchange' at the land
      ocean contact.
AB  - Land to ocean transfer of material largely controls the chemical composition of
      seawater and the global element cycles. Oceanic isotopic budgets of chemical
      species, macro- and micronutrients (e.g. Nd, Sr, Si, Mg, Zn, Mo and Ni) have
      revealed an imbalance between their sources and sinks. Radiogenic isotope budgets
      underlined the importance of taking into account continental margins as a source
      of elements to oceans. They also highlighted that the net land-ocean inputs of
      chemical species probably result from particle-dissolved exchange processes,
      named 'Boundary Exchange'. Yet, locations where 'Boundary Exchange' occurs are
      not clearly identified and reviewed here: discharge of huge amount of freshly
      weathered particles at the river mouths, submarine weathering of deposited
      sediments along the margins, submarine groundwater discharges and subterranean
      estuaries. As a whole, we conclude that all of them might contribute to 'Boundary
      Exchange'. Highlighting their specific roles and the processes at play is a key
      scientific issue for the second half of GEOTRACES.This article is part of the
      themed issue 'Biological and climatic impacts of ocean trace element chemistry'.

PMID- 29035254
TI  - Quantifying He fluxes from the mantle using multi-tracer data assimilation.
AB  - A global, coarse-resolution ocean model previously fitted to geostrophic shear
      estimates and to data of 10 hydrographic parameters and tracers has been used to
      simulate the 3He and 4He distributions resulting from the release of mantle
      helium from mid-ocean ridges. The model is in very good agreement with 14C and
      chlorofluorocarbon data and has realistic global ocean overturning strength as
      well as water mass formation and transport rates. It is found that previously
      published global mantle 3He fluxes are too high by a factor of about 2. In the
      model, optimal agreement of modelled delta3He with data is achieved for a global
      flux of 450 +/- 50 mol 3He yr-1 The formulation of He source strengths
      proportional to ridge spreading rates appears compatible with data. A model/data
      misfit analysis shows significant and large-scale delta3He underestimation in the
      southwestern Pacific centred over the Lau Backarc Basin (approx. 179 degrees 
      W/20 degrees  S). These misfits disappear in a set-up with 30 of the 450 mol yr-1
      global total 3He flux released in the Lau Basin over a depth range between 1250
      and 2500 m. Such He flux contributions are missing in present mantle He source
      compilations. Hydrothermal fluxes of other trace elements and isotopes (TEI) can
      be calculated from He fluxes on the basis of TEI : He ratios measured close to
      the sources.This article is part of the themed issue 'Biological and climatic
      impacts of ocean trace element chemistry'.

PMID- 29035255
TI  - Diagnosing oceanic nutrient deficiency.
AB  - The supply of a range of nutrient elements to surface waters is an important
      driver of oceanic production and the subsequent linked cycling of the nutrients
      and carbon. Relative deficiencies of different nutrients with respect to
      biological requirements, within both surface and internal water masses, can be
      both a key indicator and driver of the potential for these nutrients to become
      limiting for the production of new organic material in the upper ocean. The
      availability of high-quality, full-depth and global-scale datasets on the
      concentrations of a wide range of both macro- and micro-nutrients produced
      through the international GEOTRACES programme provides the potential for
      estimation of multi-element deficiencies at unprecedented scales. Resultant
      coherent large-scale patterns in diagnosed deficiency can be linked to the
      interacting physical-chemical-biological processes which drive upper ocean
      nutrient biogeochemistry. Calculations of ranked deficiencies across multiple
      elements further highlight important remaining uncertainties in the
      stoichiometric plasticity of nutrient ratios within oceanic microbial systems and
      caveats with regards to linkages to upper ocean nutrient limitation.This article
      is part of the themed issue 'Biological and climatic impacts of ocean trace
      element chemistry'.

PMID- 29035256
TI  - Impact of hydrothermalism on the ocean iron cycle.
AB  - As the iron supplied from hydrothermalism is ultimately ventilated in the iron
      limited Southern Ocean, it plays an important role in the ocean biological carbon
      pump. We deploy a set of focused sensitivity experiments with a state of the art
      global model of the ocean to examine the processes that regulate the lifetime of
      hydrothermal iron and the role of different ridge systems in governing the
      hydrothermal impact on the Southern Ocean biological carbon pump. Using GEOTRACES
      section data, we find that stabilization of hydrothermal iron is important in
      some, but not all regions. The impact on the Southern Ocean biological carbon
      pump is dominated by poorly explored southern ridge systems, highlighting the
      need for future exploration in this region. We find inter-basin differences in
      the isopycnal layer onto which hydrothermal Fe is supplied between the Atlantic
      and Pacific basins, which when combined with the inter-basin contrasts in
      oxidation kinetics suggests a muted influence of Atlantic ridges on the Southern
      Ocean biological carbon pump. Ultimately, we present a range of processes,
      operating at distinct scales, that must be better constrained to improve our
      understanding of how hydrothermalism affects the ocean cycling of iron and
      carbon.This article is part of the themed issue 'Biological and climatic impacts
      of ocean trace element chemistry'.

PMID- 29035257
TI  - Southern Ocean biological iron cycling in the pre-whaling and present ecosystems.
AB  - This study aimed to create the first model of biological iron (Fe) cycling in the
      Southern Ocean food web. Two biomass mass-balanced Ecopath models were built to
      represent pre- and post-whaling ecosystem states (1900 and 2008). Functional
      group biomasses (tonnes wet weight km-2) were converted to biogenic Fe pools (kg
      Fe km-2) using published Fe content ranges. In both models, biogenic Fe pools and
      consumption in the pelagic Southern Ocean were highest for plankton and small
      nektonic groups. The production of plankton biomass, particularly unicellular
      groups, accounted for the highest annual Fe demand. Microzooplankton contributed
      most to biological Fe recycling, followed by carnivorous zooplankton and krill.
      Biological Fe recycling matched previous estimates, and, under most conditions,
      could entirely meet the Fe demand of bacterioplankton and phytoplankton. Iron
      recycling by large baleen whales was reduced 10-fold by whaling between 1900 and
      2008. However, even under the 1900 scenario, the contribution of whales to
      biological Fe recycling was negligible compared with that of planktonic
      consumers. These models are a first step in examining oceanic-scale biological Fe
      cycling, highlighting gaps in our present knowledge and key questions for future
      research on the role of marine food webs in the cycling of trace elements in the
      sea.This article is part of the themed issue 'Biological and climatic impacts of
      ocean trace element chemistry'.

PMID- 29035258
TI  - Neodymium in the oceans: a global database, a regional comparison and
      implications for palaeoceanographic research.
AB  - The neodymium (Nd) isotopic composition of seawater has been used extensively to
      reconstruct ocean circulation on a variety of time scales. However, dissolved
      neodymium concentrations and isotopes do not always behave conservatively, and
      quantitative deconvolution of this non-conservative component can be used to
      detect trace metal inputs and isotopic exchange at ocean-sediment interfaces. In
      order to facilitate such comparisons for historical datasets, we here provide an
      extended global database for Nd isotopes and concentrations in the context of
      hydrography and nutrients. Since 2010, combined datasets for a large range of
      trace elements and isotopes are collected on international GEOTRACES section
      cruises, alongside classical nutrient and hydrography measurements. Here, we take
      a first step towards exploiting these datasets by comparing high-resolution Nd
      sections for the western and eastern North Atlantic in the context of
      hydrography, nutrients and aluminium (Al) concentrations. Evaluating those data
      in tracer-tracer space reveals that North Atlantic seawater Nd isotopes and
      concentrations generally follow the patterns of advection, as do Al
      concentrations. Deviations from water mass mixing are observed locally,
      associated with the addition or removal of trace metals in benthic nepheloid
      layers, exchange with ocean margins (i.e. boundary exchange) and/or exchange with
      particulate phases (i.e. reversible scavenging). We emphasize that the complexity
      of some of the new datasets cautions against a quantitative interpretation of
      individual palaeo Nd isotope records, and indicates the importance of spatial
      reconstructions for a more balanced approach to deciphering past ocean
      changes.This article is part of the themed issue 'Biological and climatic impacts
      of ocean trace element chemistry'.

PMID- 29035259
TI  - The oceanic budgets of nickel and zinc isotopes: the importance of sulfidic
      environments as illustrated by the Black Sea.
AB  - Isotopic data collected to date as part of the GEOTRACES and other programmes
      show that the oceanic dissolved pool is isotopically heavy relative to the inputs
      for zinc (Zn) and nickel (Ni). All Zn sinks measured until recently, and the only
      output yet measured for Ni, are isotopically heavier than the dissolved pool.
      This would require either a non-steady-state ocean or other unidentified sinks.
      Recently, isotopically light Zn has been measured in organic carbon-rich
      sediments from productive upwelling margins, providing a potential resolution of
      this issue, at least for Zn. However, the origin of the isotopically light
      sedimentary Zn signal is uncertain. Cellular uptake of isotopically light Zn
      followed by transfer to sediment does not appear to be a quantitatively important
      process. Here, we present Zn and Ni isotope data for the water column and
      sediments of the Black Sea. These data demonstrate that isotopically light Zn and
      Ni are extracted from the water column, probably through an equilibrium
      fractionation between different dissolved species followed by sequestration of
      light Zn and Ni in sulfide species to particulates and the sediment. We suggest
      that a similar, non-quantitative, process, operating in porewaters, explains the
      Zn data from organic carbon-rich sediments.This article is part of the themed
      issue 'Biological and climatic impacts of ocean trace element chemistry'.

PMID- 29035261
TI  - The effect of acidification on the bioavailability and electrochemical lability
      of zinc in seawater.
AB  - A poorly studied but potentially important consequence of the CO2-induced
      acidification of the surface ocean is a possible change in the bioavailability of
      trace metals, which play a critical role in the productivity and population
      dynamics of marine ecosystems. We report laboratory and field experiments
      designed to compare quantitatively the effects of acidification on the
      bioavailability of Zn, a metal essential to the growth of phytoplankton and on
      the extent of its complexation by model and natural ligands. We observed a good
      correspondence between the effects of pH on the rate of Zn uptake by a model
      diatom and the chemical lability of Zn measured by anodic stripping voltammetry
      (ASV). In model laboratory systems, the chemical lability and the bioavailability
      of Zn could either increase or decrease at low pH depending on the mix of
      complexing ligands. In a sample of coastal surface water, we observed similar
      increases in the ASV-labile and bioavailable Zn concentrations upon
      acidification, a result contrary to previous observations. These results, which
      can likely be generalized to other bioactive trace metals, mutatis mutandis,
      demonstrate the intricacy of the effects of ocean acidification on the chemistry
      and the ecology of surface seawater.This article is part of the themed issue
      'Biological and climatic impacts of ocean trace element chemistry'.

PMID- 29035260
TI  - Nitrite isotopes as tracers of marine N cycle processes.
AB  - Nitrite (NO2-) is a key intermediate in the marine nitrogen (N) cycle. It is
      produced and consumed throughout the ocean by the dominant processes driving the
      distribution, availability and speciation of N. However, the accumulation of
      nitrite is typically confined to depths near the base of the sunlit euphotic zone
      and in oxygen-deficient zones. These features are known as the primary and
      secondary nitrite maximum (PNM and SNM), respectively. The processes controlling
      nitrite accumulation in these features are not fully understood, but are thought
      to depend on the microbial community composition and its response to
      environmental conditions. A variety of approaches have been applied to
      understanding these features since their discovery, with the stable N and oxygen
      (O) isotope measurements of nitrite being added to this toolkit most recently.
      Large variations in nitrite N isotope ratios (15N/14N) and dramatic depletions in
      15N contrast with more consistent nitrite O isotope ratios (18O/16O) in the SNM.
      These signals provide unique information about the mechanisms of nitrite
      consumption in the SNM. By contrast, nitrite in the PNM shows less variation in
      15N/14N, but variations in 18O/16O that provide insight into the mechanisms and
      rates of N cycling there. This review presents a synthesis of nitrite isotope
      measurements in the marine environment, highlighting the insights that have been
      gained from these measurements.This article is part of the themed issue
      'Biological and climatic impacts of ocean trace element chemistry'.

PMID- 29035262
TI  - An examination of the role of particles in oceanic mercury cycling.
AB  - Recent models of global mercury (Hg) cycling have identified the downward flux of
      sinking particles in the ocean as a prominent Hg removal process from the ocean.
      At least one of these models estimates the amount of anthropogenic Hg in the
      ocean to be about 400 Mmol, with deep water formation and sinking fluxes
      representing the largest vectors by which pollutant Hg is able to penetrate the
      ocean interior. Using data from recent cruises to the Atlantic, we examined the
      dissolved and particulate partitioning of Hg in the oceanic water column as a
      cross-check on the hypothesis that sinking particle fluxes are important.
      Interestingly, these new data suggest particle-dissolved partitioning (Kd) that
      is approximately 20* greater than previous estimates, which thereby challenges
      certain assumptions about the scavenging and active partitioning of Hg in the
      ocean used in earlier models. For example, the new particle data suggest that
      regenerative scavenging is the most likely mechanism by which the association of
      Hg and particles occurs.This article is part of the themed issue 'Biological and
      climatic impacts of ocean trace element chemistry'.

PMID- 29035264
TI  - Ocean trace element cycles.

PMID- 29035263
TI  - Developing a test-bed for robust research governance of geoengineering: the
      contribution of ocean iron biogeochemistry.
AB  - Geoengineering to mitigate climate change has long been proposed, but remains
      nebulous. Exploration of the feasibility of geoengineering first requires the
      development of research governance to move beyond the conceptual towards
      scientifically designed pilot studies. Fortuitously, 12 mesoscale (approx. 1000
      km2) iron enrichments, funded to investigate how ocean iron biogeochemistry
      altered Earth's carbon cycle in the geological past, provide proxies to better
      understand the benefits and drawbacks of geoengineering. The utility of these
      iron enrichments in the geoengineering debate is enhanced by the GEOTRACES global
      survey. Here, we outline how GEOTRACES surveys and process studies can provide
      invaluable insights into geoengineering. Surveys inform key unknowns including
      the regional influence and magnitude of modes of iron supply, and stimulate iron
      biogeochemical modelling. These advances will enable quantification of
      interannual variability of iron supply to assess whether any future purposeful
      multi-year iron-fertilization meets the principle of 'additionality' (sensu Kyoto
      protocol). Process studies address issues including upscaling of geoengineering,
      and how differing iron-enrichment strategies could stimulate wide-ranging
      biogeochemical outcomes. In summary, the availability of databases on both
      mesoscale iron-enrichment studies and the GEOTRACES survey, along with modelling,
      policy initiatives and legislation have positioned the iron-enrichment approach
      as a robust multifaceted test-bed to assess proposed research into climate
      intervention.This article is part of the themed issue 'Biological and climatic
      impacts of ocean trace element chemistry'.

PMID- 29035265
TI  - Hydrothermal impacts on trace element and isotope ocean biogeochemistry.
AB  - Hydrothermal activity occurs in all ocean basins, releasing high concentrations
      of key trace elements and isotopes (TEIs) into the oceans. Importantly, the
      calculated rate of entrainment of the entire ocean volume through turbulently
      mixing buoyant hydrothermal plumes is so vigorous as to be comparable to that of
      deep-ocean thermohaline circulation. Consequently, biogeochemical processes
      active within deep-ocean hydrothermal plumes have long been known to have the
      potential to impact global-scale biogeochemical cycles. More recently, new
      results from GEOTRACES have revealed that plumes rich in dissolved Fe, an
      important micronutrient that is limiting to productivity in some areas, are
      widespread above mid-ocean ridges and extend out into the deep-ocean interior.
      While Fe is only one element among the full suite of TEIs of interest to
      GEOTRACES, these preliminary results are important because they illustrate how
      inputs from seafloor venting might impact the global biogeochemical budgets of
      many other TEIs. To determine the global impact of seafloor venting, however,
      requires two key questions to be addressed: (i) What processes are active close
      to vent sites that regulate the initial high-temperature hydrothermal fluxes for
      the full suite of TEIs that are dispersed through non-buoyant hydrothermal
      plumes? (ii) How do those processes vary, globally, in response to changing
      geologic settings at the seafloor and/or the geochemistry of the overlying ocean
      water? In this paper, we review key findings from recent work in this realm,
      highlight a series of key hypotheses arising from that research and propose a
      series of new GEOTRACES modelling, section and process studies that could be
      implemented, nationally and internationally, to address these issues.This article
      is part of the themed issue 'Biological and climatic impacts of ocean trace
      element chemistry'.

PMID- 29035266
TI  - Lead isotope exchange between dissolved and fluvial particulate matter: a
      laboratory study from the Johor River estuary.
AB  - Atmospheric aerosols are the dominant source of Pb to the modern marine
      environment, and as a result, in most regions of the ocean the Pb isotopic
      composition of dissolved Pb in the surface ocean (and in corals) matches that of
      the regional aerosols. In the Singapore Strait, however, there is a large offset
      between seawater dissolved and coral Pb isotopes and that of the regional
      aerosols. We propose that this difference results from isotope exchange between
      dissolved Pb supplied by anthropogenic aerosol deposition and adsorbed natural
      crustal Pb on weathered particles delivered to the ocean by coastal rivers. To
      investigate this issue, Pb isotope exchange was assessed through a closed-system
      exchange experiment using estuarine waters collected at the Johor River mouth
      (which discharges to the Singapore Strait). During the experiment, a known amount
      of dissolved Pb with the isotopic composition of NBS-981 (206Pb/207Pb = 1.093)
      was spiked into the unfiltered Johor water (dissolved and particulate 206Pb/207Pb
      = 1.199) and the changing isotopic composition of the dissolved Pb was monitored.
      The mixing ratio of the estuarine and spike Pb should have produced a dissolved
      206Pb/207Pb isotopic composition of 1.161, but within a week, the 206Pb/207Pb in
      the water increased to 1.190 and continued to increase to 1.197 during the next
      two months without significant changes of the dissolved Pb concentration. The
      kinetics of isotope exchange was assessed using a simple Kd model, which assumes
      multiple sub-reservoirs within the particulate matter with different exchange
      rate constants. The Kd model reproduced 56% of the observed Pb isotope variance.
      Both the closed-system experiment and field measurements imply that isotope
      exchange can be an important mechanism for controlling Pb and Pb isotopes in
      coastal waters. A similar process may occur for other trace elements.This article
      is part of the themed issue 'Biological and climatic impacts of ocean trace
      element chemistry'.

PMID- 29035267
TI  - Coastal ocean and shelf-sea biogeochemical cycling of trace elements and
      isotopes: lessons learned from GEOTRACES.
AB  - Continental shelves and shelf seas play a central role in the global carbon
      cycle. However, their importance with respect to trace element and isotope (TEI)
      inputs to ocean basins is less well understood. Here, we present major findings
      on shelf TEI biogeochemistry from the GEOTRACES programme as well as a proof of
      concept for a new method to estimate shelf TEI fluxes. The case studies focus on
      advances in our understanding of TEI cycling in the Arctic, transformations
      within a major river estuary (Amazon), shelf sediment micronutrient fluxes and
      basin-scale estimates of submarine groundwater discharge. The proposed shelf flux
      tracer is 228-radium (T1/2 = 5.75 yr), which is continuously supplied to the
      shelf from coastal aquifers, sediment porewater exchange and rivers. Model
      derived shelf 228Ra fluxes are combined with TEI/ 228Ra ratios to quantify ocean
      TEI fluxes from the western North Atlantic margin. The results from this new
      approach agree well with previous estimates for shelf Co, Fe, Mn and Zn inputs
      and exceed published estimates of atmospheric deposition by factors of
      approximately 3-23. Lastly, recommendations are made for additional GEOTRACES
      process studies and coastal margin-focused section cruises that will help refine
      the model and provide better insight on the mechanisms driving shelf-derived TEI
      fluxes to the ocean.This article is part of the themed issue 'Biological and
      climatic impacts of ocean trace element chemistry'.

PMID- 29035269
TI  - Dedication: Professor Henry (Harry) Elderfield FRS (1943-2016).

PMID- 29035268
TI  - Trace element and isotope deposition across the air-sea interface: progress and
      research needs.
AB  - The importance of the atmospheric deposition of biologically essential trace
      elements, especially iron, is widely recognized, as are the difficulties of
      accurately quantifying the rates of trace element wet and dry deposition and
      their fractional solubility. This paper summarizes some of the recent progress in
      this field, particularly that driven by the GEOTRACES, and other, international
      research programmes. The utility and limitations of models used to estimate
      atmospheric deposition flux, for example, from the surface ocean distribution of
      tracers such as dissolved aluminium, are discussed and a relatively new technique
      for quantifying atmospheric deposition using the short-lived radionuclide
      beryllium-7 is highlighted. It is proposed that this field will advance more
      rapidly by using a multi-tracer approach, and that aerosol deposition models
      should be ground-truthed against observed aerosol concentration data. It is also
      important to improve our understanding of the mechanisms and rates that control
      the fractional solubility of these tracers. Aerosol provenance and chemistry
      (humidity, acidity and organic ligand characteristics) play important roles in
      governing tracer solubility. Many of these factors are likely to be influenced by
      changes in atmospheric composition in the future. Intercalibration exercises for
      aerosol chemistry and fractional solubility are an essential component of the
      GEOTRACES programme.This article is part of the themed issue 'Biological and
      climatic impacts of ocean trace element chemistry'.

PMID- 29035271
TI  - Influence of the orbital effects on the Majorana quasi-particles in a nanowire.
AB  - Majorana quasi-particles can be realised using magnetic field in the form of
      diamagnetic (orbital) or paramagnetic effects. In both cases, the magnetic field
      induces a topologically non-trivial phase of matter. In this paper, the influence
      of orbital effects on Majorana bound states induced by paramagnetic effects in 1D
      nanowire is elaborated. The role of orbital effects in density of states and
      eigenstates of the system is also discussed. Additionally, we show the phase
      diagram-the magnetic field versus the magnetic flux, which displays a relation
      between topologically trivial and non-trivial phases. The Majorana bound states
      existence in the presence of relatively small orbital effects is indicated.

PMID- 29035270
TI  - Quantifying trace element and isotope fluxes at the ocean-sediment boundary: a
      review.
AB  - Quantifying fluxes of trace elements and their isotopes (TEIs) at the ocean's
      sediment-water boundary is a pre-eminent challenge to understand their role in
      the present, past and future ocean. There are multiple processes that drive the
      uptake and release of TEIs, and properties that determine their rates are
      unevenly distributed (e.g. sediment composition, redox conditions and
      (bio)physical dynamics). These factors complicate our efforts to find, measure
      and extrapolate TEI fluxes across ocean basins. GEOTRACES observations are
      unveiling the oceanic distributions of many TEIs for the first time. These data
      evidence the influence of the sediment-water boundary on many TEI cycles, and
      underline the fact that our knowledge of the source-sink fluxes that sustain
      oceanic distributions is largely missing. Present flux measurements provide low
      spatial coverage and only part of the empirical basis needed to predict TEI flux
      variations. Many of the advances and present challenges facing TEI flux
      measurements are linked to process studies that collect sediment cores, pore
      waters, sinking material or seawater in close contact with sediments. However,
      such sampling has not routinely been viable on GEOTRACES expeditions. In this
      article, we recommend approaches to address these issues: firstly, with an
      interrogation of emergent data using isotopic mass-balance and inverse modelling
      techniques; and secondly, by innovating pursuits of direct TEI flux measurements.
      We exemplify the value of GEOTRACES data with a new inverse model estimate of
      benthic Al flux in the North Atlantic Ocean. Furthermore, we review viable flux
      measurement techniques tailored to the sediment-water boundary. We propose that
      such activities are aimed at regions that intersect the GEOTRACES Science Plan on
      the basis of seven criteria that may influence TEI fluxes: sediment provenance,
      composition, organic carbon supply, redox conditions, sedimentation rate,
      bathymetry and the benthic nepheloid inventory.This article is part of the themed
      issue 'Biological and climatic impacts of ocean trace element chemistry'.

PMID- 29035272
TI  - Binding stability of peptides on major histocompatibility complex class I
      proteins: role of entropy and dynamics.
AB  - Prediction of peptide binding on specific human leukocyte antigens (HLA) has long
      been studied with successful results. We herein describe the effects of entropy
      and dynamics by investigating the binding stabilities of 10 nanopeptides on
      various HLA Class I alleles using a theoretical model based on molecular dynamics
      simulations. The fluctuational entropies of the peptides are estimated over a
      temperature range of 310-460 K. The estimated entropies correlate well with
      experimental binding affinities of the peptides: peptides that have higher
      binding affinities have lower entropies compared to non-binders, which have
      significantly larger entropies. The computation of the entropies is based on a
      simple model that requires short molecular dynamics trajectories and allows for
      approximate but rapid determination. The paper draws attention to the long
      neglected dynamic aspects of peptide binding, and provides a fast computation
      scheme that allows for rapid scanning of large numbers of peptides on selected
      HLA antigens, which may be useful in defining the right peptides for personal
      immunotherapy.

PMID- 29035273
TI  - Spin independent magnetoresistance effects in vertical graphene spin valves.
AB  - Vertical spin valve device configuration with multilayer graphene (MLG) as spacer
      has drawn significant attention in recent years because of its potential to
      produce large magnetoresistance (MR) effect due to perfect spin filtering.
      However, demonstration of this effect has remained elusive so far. Here we
      consider MLG vertical spin valve structures and show that they exhibit spin
      independent MR effects, which are orders of magnitude stronger than the spin
      dependent effects reported to date. These effects manifest within a moderate
      field range of 10 kG and depend on various factors such as hybridization near the
      top graphene surface, doping, defects and interlayer coupling. These effects
      highlight the rich spectrum of physical phenomena that manifest in such systems,
      which could be exploited in low to moderate magnetic field sensing applications.

PMID- 29035274
TI  - Dimension- and shape-dependent thermal transport in nano-patterned thin films
      investigated by scanning thermal microscopy.
AB  - Scanning thermal microscopy (SThM) is a technique which is often used for the
      measurement of the thermal conductivity of materials at the nanometre scale. The
      impact of nano-scale feature size and shape on apparent thermal conductivity, as
      measured using SThM, has been investigated. To achieve this, our recently
      developed topography-free samples with 200 and 400 nm wide gold wires (50 nm
      thick) of length of 400-2500 nm were fabricated and their thermal resistance
      measured and analysed. This data was used in the development and validation of a
      rigorous but simple heat transfer model that describes a nanoscopic contact to an
      object with finite shape and size. This model, in combination with a recently
      proposed thermal resistance network, was then used to calculate the SThM probe
      signal obtained by measuring these features. These calculated values closely
      matched the experimental results obtained from the topography-free sample. By
      using the model to analyse the dimensional dependence of thermal resistance, we
      demonstrate that feature size and shape has a significant impact on measured
      thermal properties that can result in a misinterpretation of material thermal
      conductivity. In the case of a gold nanowire embedded within a silicon nitride
      matrix it is found that the apparent thermal conductivity of the wire appears to
      be depressed by a factor of twenty from the true value. These results clearly
      demonstrate the importance of knowing both probe-sample thermal interactions and
      feature dimensions as well as shape when using SThM to quantify material thermal
      properties. Finally, the new model is used to identify the heat flux sensitivity,
      as well as the effective contact size of the conventional SThM system used in
      this study.

PMID- 29035275
TI  - Polynomial description of inhomogeneous topological superconducting wires.
AB  - We present the universal features of the topological invariant for p-wave
      superconducting wires after the inclusion of spatial inhomogeneities. Three
      classes of distributed potentials are studied, a single-defect, a commensurate
      and an incommensurate model, using periodic site modulations. An analytic
      polynomial description is achieved by splitting the topological invariant into
      two parts; one part depends on the chemical potential and the other does not. For
      the homogeneous case, an elliptical region is found where the topological
      invariant oscillates. The zeros of these oscillations occur at points where the
      fermion parity switches for finite wires. The increase of these oscillations with
      the inhomogeneity strength leads to new isolated non-topological phases. We
      characterize these new phases according to each class of spatial distributions.
      Such phases could also be observed in the XY model, to which our model is dual.

PMID- 29035276
TI  - Unctuous ZrO2 nanoparticles with improved functional attributes as lubricant
      additives.
AB  - One of the main drawbacks in the application of metal-oxide nanoparticles as
      lubricant additives is their poor stability in organic media, despite the good
      anti-wear, friction-reducing and high-load capacity properties described for
      these materials. In this work, we present a novel procedure to chemically cap the
      surface of ZrO2 nanoparticles (ZrO2NPs) with long hydrocarbon chains in order to
      obtain stable dispersions of ZrO2NPs in non-aqueous media without disrupting
      their attributes as lubricant additives. C-8, C-10 and C-16 saturated flexible
      chains were attached to the ZrO2NP surface and their physical and chemical
      characterization was performed by transmission electron microscopy,
      thermogravimetric analysis, attenuated total reflectance Fourier transform
      infrared spectroscopy, x-ray photoelectron spectroscopy and solid-state nuclear
      magnetic resonance. The dispersion stability of the modified ZrO2NPs in non
      aqueous media was studied using static multiple light scattering. Tribological
      tests demonstrated that dispersions of the long-chain capped ZrO2NPs in base
      lubricating oils exhibited low friction coefficients and improved the anti-wear
      properties of the base oil when compared with the raw lubricating oil.

PMID- 29035279
TI  - Cannabis in fat: high hopes to treat obesity.
AB  - Cannabinoid receptor type-1 (CB1) is known to have a substantial impact on the
      regulation of energy metabolism via central and peripheral mechanisms. In this
      issue of the JCI, Ruiz de Azua and colleagues provide important insights into the
      regulation of adipocyte physiology by CB1. Mice with adipocyte-specific deletion
      of the CB1-encoding gene had an overall improved metabolic profile in addition to
      reduced body weight and total adiposity. These changes were associated with an
      increase in sympathetic tone of the adipose tissue and expansion of activated
      macrophages, both of which occurred prior to changes in body weight, lending
      support to a causal relationship between loss of CB1 in adipocytes and systemic
      metabolic changes. This work identifies adipocyte CB1s as a potential novel
      peripheral target for affecting systemic metabolism with diminished CNS effects.

PMID- 29035277
TI  - MNK1/2 inhibition limits oncogenicity and metastasis of KIT-mutant melanoma.
AB  - Melanoma can be stratified into unique subtypes based on distinct pathologies.
      The acral/mucosal melanoma subtype is characterized by aberrant and constitutive
      activation of the proto-oncogene receptor tyrosine kinase C-KIT, which drives
      tumorigenesis. Treatment of these melanoma patients with C-KIT inhibitors has
      proven challenging, prompting us to investigate the downstream effectors of the C
      KIT receptor. We determined that C-KIT stimulates MAP kinase-interacting
      serine/threonine kinases 1 and 2 (MNK1/2), which phosphorylate eukaryotic
      translation initiation factor 4E (eIF4E) and render it oncogenic. Depletion of
      MNK1/2 in melanoma cells with oncogenic C-KIT inhibited cell migration and mRNA
      translation of the transcriptional repressor SNAI1 and the cell cycle gene CCNE1.
      This suggested that blocking MNK1/2 activity may inhibit tumor progression, at
      least in part, by blocking translation initiation of mRNAs encoding cell
      migration proteins. Moreover, we developed an MNK1/2 inhibitor (SEL201), and
      found that SEL201-treated KIT-mutant melanoma cells had lower oncogenicity and
      reduced metastatic ability. Clinically, tumors from melanoma patients harboring
      KIT mutations displayed a marked increase in MNK1 and phospho-eIF4E. Thus, our
      studies indicate that blocking MNK1/2 exerts potent antimelanoma effects and
      support blocking MNK1/2 as a potential strategy to treat patients positive for
      KIT mutations.

PMID- 29035278
TI  - Hdac3 regulates lymphovenous and lymphatic valve formation.
AB  - Lymphedema, the most common lymphatic anomaly, involves defective lymphatic valve
      development; yet the epigenetic modifiers underlying lymphatic valve
      morphogenesis remain elusive. Here, we showed that during mouse development, the
      histone-modifying enzyme histone deacetylase 3 (Hdac3) regulates the formation of
      both lymphovenous valves, which maintain the separation of the blood and
      lymphatic vascular systems, and the lymphatic valves. Endothelium-specific
      ablation of Hdac3 in mice led to blood-filled lymphatic vessels, edema, defective
      lymphovenous valve morphogenesis, improper lymphatic drainage, defective
      lymphatic valve maturation, and complete lethality. Hdac3-deficient lymphovenous
      valves and lymphatic vessels exhibited reduced expression of the transcription
      factor Gata2 and its target genes. In response to oscillatory shear stress, the
      transcription factors Tal1, Gata2, and Ets1/2 physically interacted with and
      recruited Hdac3 to the evolutionarily conserved E-box-GATA-ETS composite element
      of a Gata2 intragenic enhancer. In turn, Hdac3 recruited histone
      acetyltransferase Ep300 to form an enhanceosome complex that promoted Gata2
      expression. Together, these results identify Hdac3 as a key epigenetic modifier
      that maintains blood-lymph separation and integrates both extrinsic forces and
      intrinsic cues to regulate lymphatic valve development.

PMID- 29035281
TI  - Young endothelial cells revive aging blood.
AB  - The hematopoietic system declines with age, resulting in decreased hematopoietic
      stem cell (HSC) self-renewal capacity, myeloid skewing, and immune cell
      depletion. Aging of the hematopoietic system is associated with an increased
      incidence of myeloid malignancies and a decline in adaptive immunity. Therefore,
      strategies to rejuvenate the hematopoietic system have important clinical
      implications. In this issue of the JCI, Poulos and colleagues demonstrate that
      infusions of bone marrow (BM) endothelial cells (ECs) from young mice promoted
      HSC self-renewal and restored immune cell content in aged mice. Additionally,
      delivery of young BM ECs along with HSCs following total body irradiation
      improved HSC engraftment and enhanced survival. These results suggest an
      important role for BM endothelial cells (ECs) in regulating hematopoietic aging
      and support further research to identify the rejuvenating factors elaborated by
      BM ECs that restore HSC function and the immune repertoire in aged mice.

PMID- 29035280
TI  - Adipocyte cannabinoid receptor CB1 regulates energy homeostasis and alternatively
      activated macrophages.
AB  - Dysregulated adipocyte physiology leads to imbalanced energy storage, obesity,
      and associated diseases, imposing a costly burden on current health care.
      Cannabinoid receptor type-1 (CB1) plays a crucial role in controlling energy
      metabolism through central and peripheral mechanisms. In this work, adipocyte
      specific inducible deletion of the CB1 gene (Ati-CB1-KO) was sufficient to
      protect adult mice from diet-induced obesity and associated metabolic alterations
      and to reverse the phenotype in already obese mice. Compared with controls, Ati
      CB1-KO mice showed decreased body weight, reduced total adiposity, improved
      insulin sensitivity, enhanced energy expenditure, and fat depot-specific cellular
      remodeling toward lowered energy storage capacity and browning of white
      adipocytes. These changes were associated with an increase in alternatively
      activated macrophages concomitant with enhanced sympathetic tone in adipose
      tissue. Remarkably, these alterations preceded the appearance of differences in
      body weight, highlighting the causal relation between the loss of CB1 and the
      triggering of metabolic reprogramming in adipose tissues. Finally, the lean
      phenotype of Ati-CB1-KO mice and the increase in alternatively activated
      macrophages in adipose tissue were also present at thermoneutral conditions. Our
      data provide compelling evidence for a crosstalk among adipocytes, immune cells,
      and the sympathetic nervous system (SNS), wherein CB1 plays a key regulatory
      role.

PMID- 29035284
TI  - Traction alopecia: A neglected entity in 2017.
AB  - Traction alopecia was first described in 1904 but is still a cause of scarring
      hair loss in young women worldwide. It is unique in being initially a reversible
      then an irreversible (scarring) form of alopecia. Linked to tightly-pulled
      hairstyles, it is seen across all races. The pattern of hair loss depends on the
      style creating it but most commonly affects the frontotemporal hairline. There
      are some new examination findings associated with traction alopecia, which are
      traction folliculitis, the fringe sign and hair casts (pseudonits) on
      dermatoscopy. These may prove key in prompting early specialist referral. The
      mainstay of current treatment is cessation of the contributing hairstyles.
      Camouflage, anti-inflammatory or growth-stimulating topical preparations are
      second line treatments. In later stages of severe traction alopecia hair
      transplantation may be the only effective treatment. The evidence basis for
      medical intervention with topical agents is anecdotal at best. Furthermore,
      additional research is required to clarify the pathogenesis of this biphasic
      alopecia. Until then, prompt diagnosis and identification of causative hairstyles
      are focus of current dermatological practice.

PMID- 29035282
TI  - Endothelial transplantation rejuvenates aged hematopoietic stem cell function.
AB  - Age-related changes in the hematopoietic compartment are primarily attributed to
      cell-intrinsic alterations in hematopoietic stem cells (HSCs); however, the
      contribution of the aged microenvironment has not been adequately evaluated.
      Understanding the role of the bone marrow (BM) microenvironment in supporting HSC
      function may prove to be beneficial in treating age-related functional
      hematopoietic decline. Here, we determined that aging of endothelial cells (ECs),
      a critical component of the BM microenvironment, was sufficient to drive
      hematopoietic aging phenotypes in young HSCs. We used an ex vivo hematopoietic
      stem and progenitor cell/EC (HSPC/EC) coculture system as well as in vivo EC
      infusions following myelosuppressive injury in mice to demonstrate that aged ECs
      impair the repopulating activity of young HSCs and impart a myeloid bias.
      Conversely, young ECs restored the repopulating capacity of aged HSCs but were
      unable to reverse the intrinsic myeloid bias. Infusion of young, HSC-supportive
      BM ECs enhanced hematopoietic recovery following myelosuppressive injury and
      restored endogenous HSC function in aged mice. Coinfusion of young ECs augmented
      aged HSC engraftment and enhanced overall survival in lethally irradiated mice by
      mitigating damage to the BM vascular microenvironment. These data lay the
      groundwork for the exploration of EC therapies that can serve as adjuvant
      modalities to enhance HSC engraftment and accelerate hematopoietic recovery in
      the elderly population following myelosuppressive regimens.

PMID- 29035283
TI  - mTORC1 stimulates phosphatidylcholine synthesis to promote triglyceride
      secretion.
AB  - Liver triacylglycerol (TAG) synthesis and secretion are closely linked to
      nutrient availability. After a meal, hepatic TAG formation from fatty acids is
      decreased, largely due to a reduction in circulating free fatty acids (FFA).
      Despite the postprandial decrease in FFA-driven esterification and oxidation,
      VLDL-TAG secretion is maintained to support peripheral lipid delivery and
      metabolism. The regulatory mechanisms underlying the postprandial control of VLDL
      TAG secretion remain unclear. Here, we demonstrated that the mTOR complex 1
      (mTORC1) is essential for this sustained VLDL-TAG secretion and lipid
      homeostasis. In murine models, the absence of hepatic mTORC1 reduced circulating
      TAG, despite hepatosteatosis, while activation of mTORC1 depleted liver TAG
      stores. Additionally, mTORC1 promoted TAG secretion by regulating phosphocholine
      cytidylyltransferase alpha (CCTalpha), the rate-limiting enzyme involved in the
      synthesis of phosphatidylcholine (PC). Increasing PC synthesis in mice lacking
      mTORC1 rescued hepatosteatosis and restored TAG secretion. These data identify
      mTORC1 as a major regulator of phospholipid biosynthesis and subsequent VLDL-TAG
      secretion, leading to increased postprandial TAG secretion.

PMID- 29035285
TI  - Dermoscopy and patch testing in patients with lichen planus pigmentosus on face:
      A cross-sectional observational study in fifty Indian patients.
AB  - BACKGROUND: Lichen planus pigmentosus (LPP) is a common cause of facial melanosis
      in the dark-skinned population. At present, information on dermoscopy and patch
      testing in LPP is limited. OBJECTIVES: To describe dermoscopic findings and study
      the role of patch testing in patients with LPP on the face. METHODS: Facial
      lesions of 50 patients with LPP were studied dermoscopically, followed by
      histological evaluation. Patch and photopatch tests with the Indian Standard
      Series and Scandinavian series, respectively, and patient's own cosmetics were
      performed on all patients. RESULTS: The most common dermoscopic finding was dots
      and/or globules (43/50, 86%) in different patterns: hem-like (20.9%), arcuate
      (18.6%), incomplete reticular (39.5%), complete reticular (7%), and not otherwise
      specified (14%). Other patterns were exaggerated pseudoreticular pattern,
      accentuation of pigmentation around follicular openings, targetoid appearance,
      and obliteration of the pigmentary network. There were 26 relevant patch tests in
      17 (34%) patients: para-phenylenediamine (n = 5), nickel (n = 3), colophony,
      perfume mix and fragrance mix (n = 2 each), thiuram mix and 3,3,4,5
      tetrachlorosalicylanilide (n = 1 each), and patients' own products (n = 9). The
      only positive photopatch test was to fentichlor. No clinical or histological
      finding differed significantly based on patch test results. The only dermoscopic
      finding to be statistically associated with a positive patch test was the non
      characteristic arrangement of dots/globules (P = 0.042). LIMITATIONS: Dermoscopic
      features were not correlated with clinical features or disease duration.
      Implications of patch testing on the management of LPP cannot be commented upon
      as ours was a cross-sectional study. CONCLUSIONS: The present study describes the
      dermoscopic findings of facial lesions in LPP. Our patch test results suggest a
      probable role of allergens in causing LPP on the face.

PMID- 29035286
TI  - Urocytological evaluation of pemphigus patients on long term cyclophosphamide
      therapy: A cross sectional study.
AB  - BACKGROUND: Cyclophosphamide therapy is associated with several urological
      complications including urinary bladder malignancy. Data on urologic
      complications of chronic cyclophosphamide therapy for dermatologic conditions is
      not available. OBJECTIVES: To study the urocytological profile of pemphigus
      patients on long-term cyclophosphamide therapy. MATERIALS AND METHODS: In a cross
      sectional study, consecutive patients who had received cyclophosphamide therapy
      for pemphigus for more than 12 months were included. All patients were subjected
      to urinalysis including microscopy, culture, and urine cytology.
      Immunocytochemical staining for cytokeratin 20 (CK-20) on urine sediments and
      ELISA (enzyme-linked immunosorbent assay) for nuclear membrane protein-22 (NMP
      22) were performed in all cases. In patients with urinary symptoms, microscopic
      hematuria, or those detected with abnormal urine sediment cytology, NMP-22, and
      CK-20 positivity, cystoscopy, and other relevant investigations were also done.
      RESULTS: A total of 44 patients (43 of pemphigus vulgaris and one of pemphigus
      foliaceus) were recruited. Mean duration of cyclophosphamide intake was 2.9 +/-
      1.7 years (range 1-8 years) with a mean cumulative dose of 53 +/- 28.4 g (range
      6.5-141 g). Twenty-one cases (47.7%) each were asymptomatic and symptomatic with
      episodic urinary symptoms [of which two had urinary tract infection (UTI)] and
      two patients had gross hematuria. Urine cytology revealed mild urothelial
      nucleomegaly with hyperchromasia in four patients. However, CK-20 and NMP-22 were
      negative in all samples. Cystoscopy was performed in 21 cases and did not reveal
      any sign of bladder malignancy. LIMITATIONS: A relatively small sample size and
      lack of long-term follow-up were limitations. CONCLUSIONS: In our study, no
      serious urologic complications were found in pemphigus cases on chronic
      cyclophosphamide therapy.

PMID- 29035287
TI  - Cardio-pulmonary involvement in systemic sclerosis: A study at a tertiary care
      center.
AB  - BACKGROUND: Systemic sclerosis is a multisystem disorder characterized by
      microangiopathy, dysregulation of the immune system and massive deposition of
      collagen in the connective tissue of the skin, blood vessels and various internal
      organs. Although the mortality from renal crises has dropped significantly due to
      the use of angiotensin-converting enzyme inhibitors, cardiac and pulmonary
      involvement accounts for significant morbidity and mortality. We studied 28
      patients with systemic sclerosis at Gandhi Medical College and Hospital,
      Hyderabad, over a period of two years for cardiopulmonary involvement. AIM: The
      aim of this study was to analyze the cardiopulmonary involvement in systemic
      sclerosis. METHODS: All patients with systemic sclerosis attending the
      dermatology outpatient department were included in the study. The diagnosis of
      systemic sclerosis was made based on the American Rheumatology Association
      criteria, and was further confirmed by skin biopsy and serological
      investigations. X-ray chest, electrocardiogram, two-dimensional ECHO, high
      resolution computed tomography chest, pulmonary function tests and
      bronchoalveolar lavage were done to evaluate cardiopulmonary involvement.
      OBSERVATIONS: Out of 28 patients, 17 had diffuse systemic sclerosis and 11 had
      limited systemic sclerosis. Mean duration of symptoms was 2.9 years.
      Abnormalities in chest X-ray were found in 16 patients. Pulmonary function tests
      showed a restrictive pattern in 23 patients. High-resolution computed tomography
      of the chest showed evidence of interstitial lung disease in 21 patients, while
      five patients each had pleural effusion and cardiomegaly. Bronchoalveolar lavage
      showed different cellular patterns such as neutrophilia, eosinophilia and
      lymphocytosis. Pulmonary arterial hypertension was observed in seven patients and
      isolated pulmonary arterial hypertension in two patients. Electrocardiogram
      abnormalities were found in twenty patients. Two-dimensional ECHO was abnormal in
      17 patients with valvular abnormalities being the most common finding. Overall,
      pulmonary involvement was observed in 27 patients and cardiac involvement in 17
      patients. LIMITATIONS: A small sample size was a limitation of this study.
      Diffusing capacity of lung for carbon monoxide, and right cardiac catheterization
      were not done, as these were not available at our centre. CONCLUSIONS: In our
      patients, pulmonary involvement was more common than cardiac involvement.
      Interstitial lung disease and cardiac involvement were more commonly seen in
      diffuse systemic sclerosis whereas pulmonary hypertension was more frequent in
      limited systemic sclerosis. Hence, it is important to screen the patients for
      cardiopulmonary involvement for early diagnosis and treatment and a better
      prognostic outcome.

PMID- 29035288
TI  - Tinea barbae presenting as kerion.

PMID- 29035289
TI  - Molecular Evolution of MERS Coronavirus: Dromedaries as a Recent Intermediate
      Host or Long-Time Animal Reservoir?
AB  - While dromedary camels are the immediate animal source of MERS coronavirus (MERS
      CoV) infection, the evolutionary origin of MERS-CoV remains obscure. We analyzed
      219 camel and human MERS-CoV genome sequences available in GenBank. Phylogenetic
      analysis showed that 5 and 214 strains belong to clade A and B, respectively,
      with clade A further divided into lineage A1 (3 human strains) and lineage A2 (2
      camel strains), and clade B divided into B1 to B6 (each containing both human and
      camel strains). Recombination analysis showed potential recombination events in
      five strains from dromedaries in Saudi Arabia, with recombination between lineage
      B5 and B3 in four strains, and between lineage B3 and B4 in one strain. The spike
      protein showed the highest number of amino acid substitutions, especially between
      A2 and other lineages, and contained positively selected codons. Notably, codon
      1020 was positively selected among B and B5 strains, and can distinguish between
      clade A (Q1020) and B (R1020/H1020) strains, suggesting that this residue may
      play a role in the evolution of S protein during divergence of different
      lineages. The time of the most recent common ancestor of all MERS-CoV was dated
      to approximately 2010. The implications on the role of camels in the evolution of
      MERS-CoV are discussed.

PMID- 29035290
TI  - Relative Humidity Sensor Based on No-Core Fiber Coated by Agarose-Gel Film.
AB  - A relative humidity (RH) sensor based on single-mode-no-core-single-mode fiber
      (SNCS) structure is proposed and experimentally demonstrated. The agarose gel is
      coated on the no-core fiber (NCF) as the cladding, and multimode interference
      (MMI) occurs in the SNCS structure. The transmission spectrum of the sensor is
      modulated at different ambient relative humidities due to the tunable refractive
      index property of the agarose gel film. The relative humidity can be measured by
      the wavelength shift and intensity variation of the dip in the transmission
      spectra. The humidity response of the sensors, coated with different
      concentrations and coating numbers of the agarose solution, were experimentally
      investigated. The wavelength and intensity sensitivity is obtained as -149 pm/%RH
      and -0.075 dB/%RH in the range of 30% RH to 75% RH, respectively. The rise and
      fall time is tested to be 4.8 s and 7.1 s, respectively. The proposed sensor has
      a great potential in real-time RH monitoring.

PMID- 29035291
TI  - From Pathology to Precision Medicine in Anaplastic Large Cell Lymphoma Expressing
      Anaplastic Lymphoma Kinase (ALK+ ALCL).
AB  - Anaplastic large cell lymphoma expressing anaplastic lymphoma kinase (ALK+ ALCL)
      is a distinct subtype of non-Hodgkin lymphoma. In this review, we discuss the
      historical findings that led to its classification as a unique disease, despite
      its varied clinical presentation and histology. We discuss the molecular
      mechanisms underlying ALK+ ALCL pathology and the questions that remain in the
      field. Finally, we visit how decades of ALK+ ALCL research has yielded more
      precise drugs that hold promise for the future.

PMID- 29035292
TI  - Secreted Expression of the Cap Gene of Porcine Circovirus Type 2 in Classical
      Swine Fever Virus C-Strain: Potential of C-Strain Used as a Vaccine Vector.
AB  - Bivalent vaccines based on live attenuated viruses expressing a heterologous
      protein are an attractive strategy to address co-infections with various
      pathogens in the field. Considering the excellent efficacy and safety of the
      lapinized live attenuated vaccine C-strain (HCLV strain) of classical swine fever
      virus (CSFV), we proposed that C-strain has the potential as a viral vector for
      developing bivalent vaccines. To this end, we generated three recombinant viruses
      based on C-strain, one expressing the capsid (Cap) gene of porcine circovirus
      type 2 (PCV2) with the nuclear localization signal (NLS) (rHCLV-2ACap), and the
      other two expressing the PCV2 Cap gene without the NLS yet containing the signal
      peptide of the prolactin gene (rHCLV-pspCap) or that of the ubiquitin-specific
      peptidase gene (rHCLV-uspCap). All the recombinant viruses exhibited phenotypes
      similar to those of the parental virus and produced high-level anti-CSFV
      neutralizing antibodies (NAbs) in rabbits. Interestingly, rHCLV-uspCap and rHCLV
      pspCap, but not rHCLV-2ACap, elicited detectable anti-Cap and -PCV2 NAbs in
      rabbits. Taken together, our data demonstrate that C-strain can be used as a
      viral vector to develop bivalent vaccines.

PMID- 29035295
TI  - Nighttime Foreground Pedestrian Detection Based on Three-Dimensional Voxel
      Surface Model.
AB  - Pedestrian detection is among the most frequently-used preprocessing tasks in
      many surveillance application fields, from low-level people counting to high
      level scene understanding. Even though many approaches perform well in the
      daytime with sufficient illumination, pedestrian detection at night is still a
      critical and challenging problem for video surveillance systems. To respond to
      this need, in this paper, we provide an affordable solution with a near-infrared
      stereo network camera, as well as a novel three-dimensional foreground pedestrian
      detection model. Specifically, instead of using an expensive thermal camera, we
      build a near-infrared stereo vision system with two calibrated network cameras
      and near-infrared lamps. The core of the system is a novel voxel surface model,
      which is able to estimate the dynamic changes of three-dimensional geometric
      information of the surveillance scene and to segment and locate foreground
      pedestrians in real time. A free update policy for unknown points is designed for
      model updating, and the extracted shadow of the pedestrian is adopted to remove
      foreground false alarms. To evaluate the performance of the proposed model, the
      system is deployed in several nighttime surveillance scenes. Experimental results
      demonstrate that our method is capable of nighttime pedestrian segmentation and
      detection in real time under heavy occlusion. In addition, the qualitative and
      quantitative comparison results show that our work outperforms classical
      background subtraction approaches and a recent RGB-D method, as well as achieving
      comparable performance with the state-of-the-art deep learning pedestrian
      detection method even with a much lower hardware cost.

PMID- 29035293
TI  - Identification of (Z)-2,3-Diphenylacrylonitrileas Anti-Cancer Molecule in Persian
      Gulf Sea Cucumber Holothuria parva.
AB  - Hepatocellular carcinoma (HCC), also named cancerous hepatoma, is the most common
      type of malignant neoplasia of the liver. In this research, we screened the
      Persian Gulf sea cucumber Holothuria parva (H. parva) methanolic sub-fractions
      for the possible existence of selective toxicity on liver mitochondria isolated
      from an animal model of HCC. Next, we purified the most active fraction. Thus the
      structure of the active molecule was identified. HCC was induced by
      diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) protocol. Rat liver
      mitochondria for evaluation of the selective cytotoxic effects of sub-fractions
      of H. parva were isolated and then mitochondrial parameters were determined. Our
      results showed that C1 sub-fraction of methanolic extract of H. parva
      considerably increased reactive oxygen species (ROS) generation, collapse of
      mitochondrial membrane potential (MMP), swelling in mitochondria and cytochrome c
      release only on HCC liver mitochondria. Furthermore, the methanolic extract of H.
      parva was investigated furthermore and the active fraction was extracted. In this
      fraction, (Z)-2,3-diphenylacrylonitrile molecule, which is also known as alpha
      cyanostilbene, was identified by mass analysis. This molecule increased ROS
      generation, collapse of MMP, swelling in mitochondria and finally cytochrome c
      release only on HCC liver mitochondria. The derivatives of (Z)-2,3
      diphenylacrylonitrile in other natural products were also reported as an anti
      cancer agent. These results suggest the eligibility of the (Z)-2,3
      diphenylacrylonitrile as a complementary therapeutic agent for patients with HCC.

PMID- 29035296
TI  - A Wireless Monitoring System Using a Tunneling Sensor Array in a Smart Oral
      Appliance for Sleep Apnea Treatment.
AB  - Sleep apnea is a serious sleep disorder, and the most common type is obstructive
      sleep apnea (OSA). Untreated OSA will cause lots of potential health problems.
      Oral appliance therapy is an effective and popular approach for OSA treatment,
      but making a perfect fit for each patient is time-consuming and decreases its
      efficiency considerably. This paper proposes a System-on-a-Chip (SoC) enabled
      sleep monitoring system in a smart oral appliance, which is capable of
      intelligently collecting the physiological data about tongue movement through the
      whole therapy. A tunneling sensor array with an ultra-high sensitivity is
      incorporated to accurately detect the subtle pressure from the tongue. When the
      device is placed on the wireless platform, the temporary stored data will be
      retrieved and wirelessly transmitted to personal computers and cloud storages.
      The battery will be recharged by harvesting external RF power from the platform.
      A compact prototype module, whose size is 4.5 * 2.5 * 0.9 cm3, is implemented and
      embedded inside the oral appliance to demonstrate the tongue movement detection
      in continuous time frames. The functions of this design are verified by the
      presented measurement results. This design aims to increase efficiency and make
      it a total solution for OSA treatment.

PMID- 29035294
TI  - Predicting Amyloidogenic Proteins in the Proteomes of Plants.
AB  - Amyloids are protein fibrils with characteristic spatial structure. Though
      amyloids were long perceived to be pathogens that cause dozens of incurable
      pathologies in humans and mammals, it is currently clear that amyloids also
      represent a functionally important form of protein structure implicated in a
      variety of biological processes in organisms ranging from archaea and bacteria to
      fungi and animals. Despite their social significance, plants remain the most
      poorly studied group of organisms in the field of amyloid biology. To date,
      amyloid properties have only been demonstrated in vitro or in heterologous
      systems for a small number of plant proteins. Here, for the first time, we
      performed a comprehensive analysis of the distribution of potentially
      amyloidogenic proteins in the proteomes of approximately 70 species of land
      plants using the Waltz and SARP (Sequence Analysis based on the Ranking of
      Probabilities) bioinformatic algorithms. We analyzed more than 2.9 million
      protein sequences and found that potentially amyloidogenic proteins are abundant
      in plant proteomes. We found that such proteins are overrepresented among
      membrane as well as DNA- and RNA-binding proteins of plants. Moreover, seed
      storage and defense proteins of most plant species are rich in amyloidogenic
      regions. Taken together, our data demonstrate the diversity of potentially
      amyloidogenic proteins in plant proteomes and suggest biological processes where
      formation of amyloids might be functionally important.

PMID- 29035297
TI  - Variability in Strength, Pain, and Disability Changes in Response to an Isolated
      Lumbar Extension Resistance Training Intervention in Participants with Chronic
      Low Back Pain.
AB  - Strengthening the lumbar extensor musculature is a common recommendation for
      chronic low back pain (CLBP). Although reported as effective, variability in
      response in CLBP populations is not well investigated. This study investigated
      variability in responsiveness to isolated lumbar extension (ILEX) resistance
      training in CLBP participants by retrospective analysis of three previous
      randomized controlled trials. Data from 77 participants were available for the
      intervention arms (males = 43, females = 34) 37 participants data (males = 20,
      females = 17) from the control arms. Intervention participants had all undergone
      12 weeks of ILEX resistance training and changes in ILEX strength, pain (visual
      analogue scale; VAS), and disability (Oswestry disability index; ODI) measured.
      True inter-individual (i.e., between participants) variability in response was
      examined through calculation of difference in the standard deviation of change
      scores for both control and intervention arms. Intervention participants were
      classified into responder status using k-means cluster analysis for ILEX strength
      changes and using minimal clinically important change cut-offs for VAS and ODI.
      Change in average ILEX strength ranged 7.6 Nm (1.9%) to 192.1 Nm (335.7%). Change
      in peak ILEX strength ranged -12.2 Nm (-17.5%) to 276.6 Nm (169.6%). Participants
      were classified for strength changes as low (n = 31), medium (n = 36), and high
      responders (n = 10). Change in VAS ranged 12.0 mm to -84.0 mm. Participants were
      classified for VAS changes as negative (n = 3), non-responders (n = 34),
      responders (n = 15), and high responders (n = 19). Change in ODI ranged 18 pts to
      -45 pts. Participants were classified for ODI changes as negative (n = 2), non
      responders (n = 21), responders (n = 29), and high responders (n = 25).
      Considerable variation exists in response to ILEX resistance training in CLBP.
      Clinicians should be aware of this and future work should identify factors
      prognostic of successful outcomes.

PMID- 29035298
TI  - Molecular Docking and 3D-Pharmacophore Modeling to Study the Interactions of
      Chalcone Derivatives with Estrogen Receptor Alpha.
AB  - Tamoxifen is the most frequently used anti-estrogen adjuvant treatment for
      estrogen receptor-positive breast cancer. However, it is associated with an
      increased risk of several serious side-effects, such as uterine cancer, stroke,
      and pulmonary embolism. The 2',4'-dihydroxy-6-methoxy-3,5-dimethylchalcone
      (ChalcEA) from plant leaves of Eugenia aquea, has been found to inhibit the
      proliferation of MCF-7 human breast cancer cells in a dose-dependent manner, with
      an IC50 of 74.5 MUg/mL (250 MUM). The aim of this work was to study the molecular
      interactions of new ChalcEA derivatives formed with the Estrogen Receptor alpha
      (ERalpha) using computer aided drug design approaches. Molecular docking using
      Autodock 4.2 was employed to explore the modes of binding of ChalcEA derivatives
      with ERalpha. The 3D structure-based pharmacophore model was derived using
      LigandScout 4.1 Advanced to investigate the important chemical interactions of
      the ERalpha-tamoxifen complex structure. The binding energy and the tamoxifen
      pharmacophore fit score of the best ChalcEA derivative (HNS10) were -12.33
      kcal/mol and 67.07 kcal/mol, respectively. The HNS10 interacted with Leu346,
      Thr347, Leu349, Ala350, Glu353, Leu387, Met388, Leu391, Arg394, Met421, and
      Leu525. These results suggest that the new ChalcEA derivatives could serve as the
      lead compound for potent ERalpha inhibitor in the fight against breast cancer.

PMID- 29035300
TI  - Photometric and Colorimetric Assessment of LED Chip Scale Packages by Using a
      Step-Stress Accelerated Degradation Test (SSADT) Method.
AB  - By solving the problem of very long test time on reliability qualification for
      Light-emitting Diode (LED) products, the accelerated degradation test with a
      thermal overstress at a proper range is regarded as a promising and effective
      approach. For a comprehensive survey of the application of step-stress
      accelerated degradation test (SSADT) in LEDs, the thermal, photometric, and
      colorimetric properties of two types of LED chip scale packages (CSPs), i.e.,
      4000  degrees K and 5000  degrees K samples each of which was driven by two
      different levels of currents (i.e., 120 mA and 350 mA, respectively), were
      investigated under an increasing temperature from 55  degrees C to 150  degrees C
      and a systemic study of driving current effect on the SSADT results were also
      reported in this paper. During SSADT, junction temperatures of the test samples
      have a positive relationship with their driving currents. However, the
      temperature-voltage curve, which represents the thermal resistance property of
      the test samples, does not show significant variance as long as the driving
      current is no more than the sample's rated current. But when the test sample is
      tested under an overdrive current, its temperature-voltage curve is observed as
      obviously shifted to the left when compared to that before SSADT. Similar
      overdrive current affected the degradation scenario is also found in the
      attenuation of Spectral Power Distributions (SPDs) of the test samples. As used
      in the reliability qualification, SSADT provides explicit scenes on color shift
      and correlated color temperature (CCT) depreciation of the test samples, but not
      on lumen maintenance depreciation. It is also proved that the varying rates of
      the color shift and CCT depreciation failures can be effectively accelerated with
      an increase of the driving current, for instance, from 120 mA to 350 mA. For
      these reasons, SSADT is considered as a suitable accelerated test method for
      qualifying these two failure modes of LED CSPs.

PMID- 29035299
TI  - Two Distinct Conformations in Bet v 2 Determine Its Proteolytic Resistance to
      Cathepsin S.
AB  - Birch pollen allergy affects more than 20% of the European allergic population.
      On a molecular level, birch pollen allergy can be linked to the two dominant
      allergens Bet v 1 and Bet v 2. Bet v 2 belongs to the profilin family, which is
      abundant in the plant kingdom. Importantly, the homologous plant profilins have a
      conserved cysteine motif with a currently unknown functional relevance. In
      particular, it is unknown whether the motif is relevant for disulfide formation
      and to what extent it would affect the profilins' structural, functional and
      immunological properties. Here we present crystal structures of Bet v 2 in the
      reduced and the oxidized state, i.e., without and with a disulfide bridge.
      Despite overall structural similarity, the two structures distinctly differ at
      their termini which are stabilized to each other in the oxidized, i.e., disulfide
      linked state. These structural differences translate into differences in their
      proteolytic resistance. Whereas the oxidized Bet v 2 is rather resistant towards
      the endolysosomal protease cathepsin S, it is rapidly degraded in the reduced
      form. By contrast, both Bet v 2 forms exhibit similar immunological properties as
      evidenced by their binding to IgE antibodies from birch pollen allergic patients
      and by their ability to trigger histamine release in a humanized rat basophilic
      leukemia cells (RBL) assay, independent of the presence or absence of the
      disulfide bridge. Taken together our findings suggest that the oxidized Bet v 2
      conformation should be the relevant species, with a much longer retention time to
      trigger immune responses.

PMID- 29035301
TI  - Exploring Knowledge and Attitudes about Vitamin D among Adults in Saudi Arabia: A
      Qualitative Study.
AB  - Abstract: Vitamin D deficiency is widespread in Saudi Arabia. The aim of this
      study was to explore participants' knowledge about vitamin D and attitudes toward
      sun exposure. The study also aimed to explore the social and cultural factors
      that might potentially contribute to vitamin D deficiency in Saudi Arabia. Face
      to-face interviews were carried out in the cities of Jeddah and Makkah between
      May and October 2015. The interview questions were semi-structured, and the data
      was analyzed using thematic analysis. Study participants showed a reasonable
      level of knowledge in different areas about vitamin D, including the effect of
      vitamin D deficiency on bone health and exposure to sunlight as the main source
      of vitamin D. Participants were also knowledgeable about vitamin D supplements as
      another source of this vitamin. Nevertheless, there was a shortage of knowledge
      in relation to dietary sources of vitamin D. In respect to attitudes toward sun
      exposure, some participants had positive attitudes toward sunlight and were
      willing to expose themselves to sunlight, but it was restricted to the early
      morning or late afternoon to avoid the heat. These participants who liked
      exposure to sunlight were largely exposing only their faces and hands to
      sunlight. Other participants had negative attitudes toward sun exposure and were
      avoiding sunlight. Moreover, the study participants identified several barriers
      to sun exposure, including hot climate, living in high-rise buildings, limited
      public areas allowing outdoor activities, lifestyle issues such as physical
      inactivity, and some religious concerns such as wearing the hijab. The study
      results also demonstrate that females were more enthusiastic about taking actions
      to improve their vitamin D status in comparison with males. Recommendations for
      health education interventions that increase awareness about vitamin D sources,
      especially food sources, are made. Also, educational interventions should focus
      on increasing awareness about the sufficient time of the day and duration for sun
      exposure to improve vitamin D status and the importance of the intake of vitamin
      D supplements as an affordable source to improve vitamin D status. Increasing
      males' awareness of the benefits of vitamin D is important to encourage them to
      adopt behaviors to improve vitamin D.

PMID- 29035302
TI  - Oligoarticular Hemarthroses and Osteomyelitis Complicating Pasteurella Meningitis
      in an Infant.
AB  - A 5-month-old previously healthy female presented with a one-week history of
      fever and increased fussiness. Her presentation revealed an ill-appearing infant
      with an exam and cerebrospinal fluid (CSF) studies concerning bacterial
      meningitis; CSF cultures grew Pasteurella multocida. Additionally, brain magnetic
      resonance imaging (MRI) demonstrated cervical osteomyelitis. Despite multiple
      days of antibiotic therapy, she remained febrile with continued pain; MRI showed
      oligoarticular effusions, and aspiration of these joints yielded bloody
      aspirates. Evaluations for coagulopathy and immune complex-mediated arthropathy
      were negative. The patient improved following appropriate antibiotic therapy and
      spontaneous resolution of hemarthroses, and was discharged to a short-term
      rehabilitation hospital. P. multocida is a small, encapsulated coccobacillus that
      is part of the commensal oral flora of animals. It most commonly causes skin
      infections in humans, yet is a rare cause of meningitis in the pediatric
      population, especially in children <1 year of age. Transmission due to P.
      multocida is most commonly due to direct contact with animals. To our knowledge,
      this is the first case of oligoarticular hemarthroses and cervical osteomyelitis
      complicating P multocida meningitis. This case highlights the physician's
      potential for cognitive bias and premature anchoring, and the resulting
      implications in delivering excellent patient care.

PMID- 29035303
TI  - Optimization of Bicomponent Electrospun Fibers for Therapeutic Use: Post
      Treatments to Improve Chemical and Biological Stability.
AB  - Bicomponent electrospun nanofibers based on the combination of synthetic (i.e.,
      aliphatic polyesters such as polycaprolactone (PCL)) and natural proteins (i.e.,
      gelatin) have been extensively investigated as temporary platforms to instruct
      cells by the release of molecular/pharmaceutical signals for the regeneration of
      several tissues. Here, water soluble proteins (i.e., gelatin), strictly embedded
      to PCL, act as carriers of bioactive molecules, thus improving bioavailability
      and supporting cell activities during in vitro regeneration. However, these
      proteins are rapidly digested by enzymes, locally produced by many different cell
      types, both in vitro and in vivo, with significant drawbacks in the control of
      molecular release. Hence, we have investigated three post-processing strategies
      based on the use of different crosslinking agents-(1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide hydrochloride) (EDC), glyceraldehyde (GC), and
      1,4-butanediol diglycidyl ether (BDDGE)-to delay the dissolution time of gelatin
      macromolecules from bicomponent fibers. All of the qualitative (i.e., SEM, TGA)
      and quantitative (i.e., Trinitrobenzene sulfonate (TNBS) and bicinchoninic acid
      (BCA) assays) morphological/chemical analyses as well as biocompatibility assays
      indicate that EDC crosslinking improves the chemical stability of bicomponent
      fibers at 37  degrees C and provides a more efficient encapsulation and
      controlled sustained release of drug, thus resulting in the best post-treatment
      to design bio-inspired fibrous platforms for the extended in vitro release of
      drugs.

PMID- 29035304
TI  - Introduction to the Toxins Special Issue on LC-MS/MS Methods for Mycotoxin
      Analysis.
AB  - Various filamentous fungi can produce secondary metabolites, whose biochemical
      significance in fungal growth and development has not always been fully
      clarified; however, some of these metabolites can cause deleterious effects on
      other organisms and are classified as mycotoxins [...].

PMID- 29035305
TI  - NIR Rapid Assessments of Blumea balsamifera (Ai-na-xiang) in China.
AB  - Blumea balsamifera (Ai-na-xiang) is used as an important plant source of natural
      borneol, which is widely used in the pharmaceutical industry. The aim of this
      study was to establish the methods based on near infrared (NIR) spectroscopy for
      determining the geographical origin of B. balsamifera, as well as developing a
      method for the quantitative rapid analysis of the active pharmaceutical
      ingredients (APIs). A total of 109 samples were collected from China in 2013 and
      arbitrarily divided into calibration and prediction sets using the Kennard-Stone
      algorithm. The l-borneol and total flavone contents of the samples were measured
      by gas chromatography and ultraviolet-visible spectroscopy, respectively. The NIR
      spectra were acquired using an integrating sphere and a partial least squares
      (PLS) model was built using the optimum wavelength regions, which were selected
      using a synergy interval partial least-squares (SiPLS) algorithm. The root mean
      square errors of prediction of the l-borneol and total flavone models were 0.0779
      and 2.2694 mg/g, with R2 of 0.9069 and 0.8013, respectively. A discriminant model
      to determine the geographical origin of B. balsamifera (Guizhou and Hainan) was
      also established using a partial least squares discriminant analysis method with
      an optimum pretreatment method. The prediction accuracy rate of the model was
      100%. NIR spectroscopy can be used as a reliable and environmentally friendly
      method to determine the API and the origin of different B. balsamifera samples.

PMID- 29035307
TI  - Effects of Three Lipidated Oxytocin Analogs on Behavioral Deficits in CD38
      Knockout Mice.
AB  - Oxytocin (OT) is a nonapeptide that plays an important role in social behavior.
      Nasal administration of OT has been shown to improve trust in healthy humans and
      social interaction in autistic subjects. As is consistent with the nature of a
      peptide, OT has some unfavorable characteristics: it has a short half-life in
      plasma and shows poor permeability across the blood-brain barrier. Analogs with
      long-lasting effects may overcome these drawbacks. To this end, we have
      synthesized three analogs: lipo-oxytocin-1 (LOT-1), in which two palmitoyl groups
      are conjugated to the cysteine and tyrosine residues, lipo-oxytocin-2 (LOT-2) and
      lipo-oxytocin-3 (LOT-3), which include one palmitoyl group conjugated at the
      cysteine or tyrosine residue, respectively. The following behavioral deficits
      were observed in CD38 knockout (CD38-/-) mice: a lack of paternal nurturing in
      CD38-/- sires, decreased ability for social recognition, and decreased sucrose
      consumption. OT demonstrated the ability to recover these disturbances to the
      level of wild-type mice for 30 min after injection. LOT-2 and LOT-3 partially
      recovered the behaviors for a short period. Conversely, LOT-1 restored the
      behavioral parameters, not for 30 min, but for 24 h. These data suggest that the
      lipidation of OT has some therapeutic benefits, and LOT-1 would be most useful
      because of its long-last activity.

PMID- 29035306
TI  - Platelet Endothelial Cell Adhesion Molecule-1 and Oligodendrogenesis:
      Significance in Alcohol Use Disorders.
AB  - Alcoholism is a chronic relapsing disorder with few therapeutic strategies that
      address the core pathophysiology. Brain tissue loss and oxidative damage are key
      components of alcoholism, such that reversal of these phenomena may help break
      the addictive cycle in alcohol use disorder (AUD). The current review focuses on
      platelet endothelial cell adhesion molecule 1 (PECAM-1), a key modulator of the
      cerebral endothelial integrity and neuroinflammation, and a targetable
      transmembrane protein whose interaction within AUD has not been well explored.
      The current review will elaborate on the function of PECAM-1 in physiology and
      pathology and infer its contribution in AUD neuropathology. Recent research
      reveals that oligodendrocytes, whose primary function is myelination of neurons
      in the brain, are a key component in new learning and adaptation to environmental
      challenges. The current review briefly introduces the role of oligodendrocytes in
      healthy physiology and neuropathology. Importantly, we will highlight the recent
      evidence of dysregulation of oligodendrocytes in the context of AUD and then
      discuss their potential interaction with PECAM-1 on the cerebral endothelium.

PMID- 29035310
TI  - A Sub-Microanalysis Approach in Chemical Characterisation of Gold Nanorods Formed
      by a Novel Polymer-Immobilised Gold Seeds Base.
AB  - Gold nanorods (GNRs) have been fabricated by a novel polymer-immobilised seed
      mediated method using ultraviolet (UV) photoreduced gold-polymethylmethacrylate
      (Au-PMMA) nanocomposites as a seed platform and characterised at sub-micron scale
      regime with synchrotron-based techniques; near-edge X-ray absorption fine
      structure (NEXAFS) spectroscopy and X-ray fluorescence (XRF) mapping. In this
      report, it is shown that investigating polymer nanocomposites using combination
      of XRF mapping and NEXAFS spectromicroscopy can help to see the growth phenomenon
      from different perspective than conventional characterisation techniques. XRF
      maps are used to explore distribution of the constituent elements and showing how
      polymer matrix making stripe patterns along with regions where GNRs are formed.
      NEXAFS carbon (C) K-edge spectra have been taken at three different stages of
      synthesis: (1) on Au-PMMA nanocomposites before UV irradiation, (2) after gold
      nanoparticles formation, and (3) after GNRs formation. It reveals how polymer
      matrix has been degraded during GNRs formation and avoiding chemically or
      physically damage to polymer matrix is crucial to control the formation of GNRs.

PMID- 29035311
TI  - Modeling of Interactions between the Zebrafish Hatching Enzyme ZHE1 and A Series
      of Metal Oxide Nanoparticles: Nano-QSAR and Causal Analysis of Inactivation
      Mechanisms.
AB  - The quantitative relationships between the activity of zebrafish ZHE1 enzyme and
      a series of experimental and physicochemical features of 24 metal oxide
      nanoparticles were revealed. Vital characteristics of the nanoparticles'
      structure were reflected using both experimental and theoretical descriptors. The
      developed quantitative structure-activity relationship model for nanoparticles
      (nano-QSAR) was capable of predicting the enzyme inactivation based on four
      descriptors: the hydrodynamic radius, mass density, the Wigner-Seitz radius, and
      the covalent index. The nano-QSAR model was calculated using the non-linear
      regression tree M5P algorithm. The developed model is characterized by high
      robustness R2bagging = 0.90 and external predictivity Q2EXT = 0.93. This model is
      in agreement with modern theories of aquatic toxicity. Dissolution and size
      dependent characteristics are among the key driving forces for enzyme
      inactivation. It was proven that ZnO, CuO, Cr2O3, and NiO nanoparticles
      demonstrated strong inhibitory effects because of their solubility. The proposed
      approach could be used as a non-experimental alternative to animal testing.
      Additionally, methods of causal discovery were applied to shed light on the
      mechanisms and modes of action.

PMID- 29035312
TI  - Temperature Dependence of the Resonant Magnetoelectric Effect in Layered
      Heterostructures.
AB  - The dependence of the resonant direct magnetoelectric effect on temperature is
      studied experimentally in planar composite structures. Samples of rectangular
      shapes with dimensions of 5 mm * 20 mm employed ferromagnetic layers of either an
      amorphous (metallic glass) alloy or nickel with a thickness of 20-200 MUm and
      piezoelectric layers of single crystalline langatate material or lead zirconate
      titanate piezoelectric ceramics with a thickness of 500 MUm. The temperature of
      the samples was varied in a range between 120 and 390 K by blowing a gaseous
      nitrogen stream around them. It is shown that the effective characteristics of
      the magnetoelectric effect-such as the mechanical resonance frequency fr, the
      quality factor Q and the magnitude of the magnetoelectric coefficient alphaE at
      the resonance frequency-are contingent on temperature. The interrelations between
      the temperature changes of the characteristics of the magnetoelectric effect and
      the temperature variations of the following material parameters-Young's modulus
      Y, the acoustic quality factor of individual layers, the dielectric constant
      epsilon, the piezoelectric modulus d of the piezoelectric layer as well as the
      piezomagnetic coefficients lambda(n) of the ferromagnetic layer-are established.
      The effect of temperature on the characteristics of the nonlinear magnetoelectric
      effect is observed for the first time. The results can be useful for designing
      magnetoelectric heterostructures with specified temperature characteristics, in
      particular, for the development of thermally stabilized magnetoelectric devices.

PMID- 29035308
TI  - Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanisms and
      Therapy.
AB  - The gut microbiota plays critical roles in development of obese-related metabolic
      diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes(T2D),
      and insulin resistance(IR), highlighting the potential of gut microbiota-targeted
      therapies in these diseases. There are various ways that gut microbiota can be
      manipulated, including through use of probiotics, prebiotics, synbiotics,
      antibiotics, and some active components from herbal medicines. In this review, we
      review the main roles of gut microbiota in mediating the development of NAFLD,
      and the advances in gut microbiota-targeted therapies for NAFLD in both the
      experimental and clinical studies, as well as the conclusions on the prospect of
      gut microbiota-targeted therapies in the future.

PMID- 29035309
TI  - Serum Magnesium Levels in Preterm Infants Are Higher Than Adult Levels: A
      Systematic Literature Review and Meta-Analysis.
AB  - Magnesium (Mg) is an essential mineral in the body, impacting the synthesis of
      biomacromolecules, bone matrix development, energy production, as well as heart,
      nerve, and muscle function. Although the importance of Mg is evident, reference
      values for serum Mg (sMg) in pediatric patients (more specifically, in neonates)
      are not well established. This systematic literature review and meta-analysis
      (using 47 eligible studies) aims to quantify normal and tolerable ranges of sMg
      concentrations during the neonatal period and to highlight the factors
      influencing Mg levels and the importance of regulating sMg levels during
      pregnancy and birth. In newborns without Mg supplementation during pregnancy,
      magnesium levels at birth (0.76 (95% CI: 0.52, 0.99) mmol/L) were similar to that
      of mothers during pregnancy (0.74 (95% CI: 0.43, 1.04) mmol/L), but increased
      during the first week of life (0.91 (95% CI: 0.55, 1.26) mmol/L) before returning
      to adult levels. This pattern was also seen in newborns with Mg supplementation
      during pregnancy, where the average was 1.29 (95% CI: 0.50, 2.08) mmol/L at birth
      and 1.44 (95% CI: 0.61, 2.27) mmol/L during the first week of life. Factors
      influencing these levels include prenatal Mg supplementation, gestational age,
      birth weight, renal maturity/function, and postnatal Mg intake. Elevated Mg
      levels (>2.5 mmol/L) have been associated with an increased risk of mortality,
      admission into intensive care, hypotonia, hypotension, and respiratory depression
      but sMg concentrations up to 2.0 mmol/L appear to be well tolerated in neonates,
      requiring adequate survey and minimal intervention.

PMID- 29035313
TI  - Microstructural Modification and Characterization of Sericite.
AB  - Activated sericite was prepared by thermal modification, acid activation and
      sodium modification, and it was characterized by X-ray diffraction (XRD)
      analysis, differential scanning calorimetry (DSC), N2 adsorption test, thermo
      gravimetric analysis (TGA), nuclear magnetic resonance (NMR), and scanning
      electron microscope (SEM). The results indicated that the crystallinity of raw
      sericite decreased after thermal modification; the pores with sizes between 5 nm
      to 10 nm of thermal-modified sericite have collapsed and the surface area
      increased after thermal modification. The dissolving-out amount of Al3+ reached
      ca. 31 mg/g in the optimal processing conditions during acid activation; cation
      exchange capacity (CEC) of acid-treated sericite increased to 56.37 mmol/100 g
      meq/g after sodium modification compared with that of raw sericite (7.42 mmol/100
      g). The activated sericite is a promising matrix for clay-polymer nanocomposites.

PMID- 29035315
TI  - Breaking Up Sitting with Light-Intensity Physical Activity: Implications for
      Shift-Workers.
AB  - Prolonged sitting, restricted sleep, and circadian disruption are all independent
      risk factors for non-communicable diseases. Previous research has demonstrated
      that breaking up sitting with light-intensity physical activity has clear
      benefits for the health of day workers, but these findings may not apply in the
      presence of sleep restriction and/or circadian disruption-both of which are
      commonly experienced by shift-workers. Specifically, sleep restriction, and
      circadian disruption result in acute physiological changes that may offset the
      benefits of breaking up sitting. This commentary will explore the potential
      benefits of breaking up sitting for health, work performance, and subsequent
      sleep in shift-workers. Future areas of research designed to understand the
      mechanisms by which prolonged sitting and shift work impact worker health and
      safety and to support the design of effective occupational health and safety
      interventions are proposed.

PMID- 29035314
TI  - Animal Toxins Providing Insights into TRPV1 Activation Mechanism.
AB  - Beyond providing evolutionary advantages, venoms offer unique research tools, as
      they were developed to target functionally important proteins and pathways. As a
      key pain receptor in the nociceptive pathway, transient receptor potential
      vanilloid 1 (TRPV1) of the TRP superfamily has been shown to be a target for
      several toxins, as a way of producing pain to deter predators. Importantly, TRPV1
      is involved in thermoregulation, inflammation, and acute nociception. As such,
      toxins provide tools to understand TRPV1 activation and modulation, a critical
      step in advancing pain research and the development of novel analgesics. Indeed,
      the phytotoxin capsaicin, which is the spicy chemical in chili peppers, was
      invaluable in the original cloning and characterization of TRPV1. The unique
      properties of each subsequently characterized toxin have continued to advance our
      understanding of functional, structural, and biophysical characteristics of
      TRPV1. By building on previous reviews, this work aims to provide a comprehensive
      summary of the advancements made in TRPV1 research in recent years by employing
      animal toxins, in particular DkTx, RhTx, BmP01, Echis coloratus toxins, APHCs and
      HCRG21. We examine each toxin's functional aspects, behavioral effects, and
      structural features, all of which have contributed to our current knowledge of
      TRPV1. We additionally discuss the key features of TRPV1's outer pore domain,
      which proves to be the target of the currently discussed toxins.

PMID- 29035316
TI  - Non-Traditional Risk Factors of Albuminuria in the Pediatric Population: A
      Scoping Review.
AB  - The presence of albumin in urine has been used for more than four decades as a
      marker of renal and cardiovascular damage. Most of the information on this marker
      is related to adults. The prevalence of albuminuria in the pediatric population
      has been reported as being 2.2-12.8% in some countries. Most research in this
      field is related to albuminuria and diseases, such as diabetes and hypertension.
      Using the methodology described by Arksey and O'Malley in 2005, a scoping review
      was carried out to show that the presence of albumin in urine in the pediatric
      population might be associated with environmental, demographic, congenital,
      infectious, and non-infectious factors. The information collected is supported by
      74 references present in PubMed. The results reveal the multiple causes
      associated with albuminuria in the pediatric population. This information can be
      very useful for clinical practice by adding knowledge about albuminuria behavior
      in children.

PMID- 29035317
TI  - Systematic Review: Land Cover, Meteorological, and Socioeconomic Determinants of
      Aedes Mosquito Habitat for Risk Mapping.
AB  - Asian tiger and yellow fever mosquitoes (Aedes albopictus and Ae. aegypti) are
      global nuisances and are competent vectors for viruses such as Chikungunya
      (CHIKV), Dengue (DV), and Zika (ZIKV). This review aims to analyze available
      spatiotemporal distribution models of Aedes mosquitoes and their influential
      factors. A combination of five sets of 3-5 keywords were used to retrieve all
      relevant published models. Five electronic search databases were used: PubMed,
      MEDLINE, EMBASE, Scopus, and Google Scholar through 17 May 2017. We generated a
      hierarchical decision tree for article selection. We identified 21 relevant
      published studies that highlight different combinations of methodologies, models
      and influential factors. Only a few studies adopted a comprehensive approach
      highlighting the interaction between environmental, socioeconomic, meteorological
      and topographic systems. The selected articles showed inconsistent findings in
      terms of number and type of influential factors affecting the distribution of
      Aedes vectors, which is most likely attributed to: (i) limited availability of
      high-resolution data for physical variables, (ii) variation in sampling methods;
      Aedes feeding and oviposition behavior; (iii) data collinearity and statistical
      distribution of observed data. This review highlights the need and sets the stage
      for a rigorous multi-system modeling approach to improve our knowledge about
      Aedes presence/abundance within their flight range in response to the interaction
      between environmental, socioeconomic, and meteorological systems.

PMID- 29035318
TI  - The Role of the S40 Gene Family in Leaf Senescence.
AB  - Senescence affect different traits of plants, such as the ripening of fruit,
      number, quality and timing of seed maturation. While senescence is induced by
      age, growth hormones and different environmental stresses, a highly organized
      genetic mechanism related to substantial changes in gene expression regulates the
      process. Only a few genes associated to senescence have been identified in crop
      plants despite the vital significance of senescence for crop yield. The S40 gene
      family has been shown to play a role in leaf senescence. The barley HvS40 gene is
      one of the senescence marker genes which shows expression during age-dependent as
      well as dark-induced senescence. Like barley HvS40, the Arabidopsis AtS40-3 gene
      is also induced during natural senescence as well as in response to treatment
      with abscisic acid, salicylic acid, darkness and pathogen attack. It is
      speculated that rice OsS40 has a similar function in the leaf senescence of rice.

PMID- 29035320
TI  - Personomics: The Missing Link in the Evolution from Precision Medicine to
      Personalized Medicine.
AB  - Clinical practice guidelines have been developed for many common conditions based
      on data from randomized controlled trials. When medicine is informed solely by
      clinical practice guidelines, however, the patient is not treated as an
      individual, but rather a member of a group. Precision medicine, as defined
      herein, characterizes unique biological characteristics of the individual or of
      specimens obtained from an individual to tailor diagnostics and therapeutics to a
      specific patient. These unique biological characteristics are defined by the
      tools of precision medicine: genomics, proteomics, metabolomics, epigenomics,
      pharmacogenomics, and other "-omics." Personalized medicine, as defined herein,
      uses additional information about the individual derived from knowing the patient
      as a person. These unique personal characteristics are defined by tools known as
      personomics which takes into account an individual's personality, preferences,
      values, goals, health beliefs, social support network, financial resources, and
      unique life circumstances that affect how and when a given health condition will
      manifest in that person and how that condition will respond to treatment. In this
      paradigm, precision medicine may be considered a necessary step in the evolution
      of medical care to personalized medicine, with personomics as the missing link.

PMID- 29035319
TI  - Nutritional Therapy in Liver Transplantation.
AB  - Protein-energy malnourishment is commonly encountered in patients with end-stage
      liver disease who undergo liver transplantation. Malnutrition may further
      increase morbidity, mortality and costs in the post-transplantation setting. The
      importance of carefully assessing the nutritional status during the work-up of
      patients who are candidates for liver replacement is widely recognized. The
      metabolic abnormalities induced by liver failure render the conventional
      assessment of nutritional status to be challenging. Preoperative loss of skeletal
      muscle mass, namely, sarcopenia, has a significant detrimental impact on post
      transplant outcomes. It is essential to provide sufficient nutritional support
      during all phases of liver transplantation. Oral nutrition is preferred, but tube
      enteral nutrition may be required to provide the needed energy intake. Herein,
      the latest currently employed perioperative nutritional interventions in liver
      transplant recipients are thoroughly illustrated including synbiotics,
      micronutrients, branched-chain amino acid supplementation, immunonutrition
      formulas, fluid and electrolyte balance, the offering of nocturnal meals, dietary
      counselling, exercise and rehabilitation.

PMID- 29035322
TI  - Analysis of Genetic Diversity and Structure Pattern of Indigofera Pseudotinctoria
      in Karst Habitats of the Wushan Mountains Using AFLP Markers.
AB  - Indigofera pseudotinctoria Mats is an agronomically and economically important
      perennial legume shrub with a high forage yield, protein content and strong
      adaptability, which is subject to natural habitat fragmentation and serious human
      disturbance. Until now, our knowledge of the genetic relationships and
      intraspecific genetic diversity for its wild collections is still poor,
      especially at small spatial scales. Here amplified fragment length polymorphism
      (AFLP) technology was employed for analysis of genetic diversity,
      differentiation, and structure of 364 genotypes of I. pseudotinctoria from 15
      natural locations in Wushan Montain, a highly structured mountain with typical
      karst landforms in Southwest China. We also tested whether eco-climate factors
      has affected genetic structure by correlating genetic diversity with habitat
      features. A total of 515 distinctly scoreable bands were generated, and 324 of
      them were polymorphic. The polymorphic information content (PIC) ranged from
      0.694 to 0.890 with an average of 0.789 per primer pair. On species level, Nei's
      gene diversity (Hj), the Bayesian genetic diversity index (HB) and the Shannon
      information index (I) were 0.2465, 0.2363 and 0.3772, respectively. The high
      differentiation among all sampling sites was detected (FST = 0.2217, GST =
      0.1746, G'ST = 0.2060, thetaB = 0.1844), and instead, gene flow among accessions
      (Nm = 1.1819) was restricted. The population genetic structure resolved by the
      UPGMA tree, principal coordinate analysis, and Bayesian-based cluster analyses
      irrefutably grouped all accessions into two distinct clusters, i.e., lowland and
      highland groups. The population genetic structure resolved by the UPGMA tree,
      principal coordinate analysis, and Bayesian-based cluster analyses irrefutably
      grouped all accessions into two distinct clusters, i.e., lowland and highland
      groups. This structure pattern may indicate joint effects by the neutral
      evolution and natural selection. Restricted Nm was observed across all
      accessions, and genetic barriers were detected between adjacent accessions due to
      specifically geographical landform.

PMID- 29035324
TI  - A Mesoscopic Analytical Model to Predict the Onset of Wrinkling in Plain Woven
      Preforms under Bias Extension Shear Deformation.
AB  - A mesoscopic analytical model of wrinkling of Plain-Woven Composite Preforms
      (PWCPs) under the bias extension test is presented, based on a new instability
      analysis. The analysis is aimed to facilitate a better understanding of the
      nature of wrinkle formation in woven fabrics caused by large in-plane shear,
      while it accounts for the effect of fabric and process parameters on the onset of
      wrinkling. To this end, the mechanism of wrinkle formation in PWCPs in mesoscale
      is simplified and an equivalent structure composed of bars and different types of
      springs is proposed, mimicking the behavior of a representative PWCP element at
      the post-locking state. The parameters of this equivalent structure are derived
      based on geometric and mechanical characteristics of the PWCP. The principle of
      minimum total potential energy is employed to formluate the model, and
      experimental validation is carried out to reveal the effectiveness of the derived
      wrinkling prediction equation.

PMID- 29035321
TI  - A Novel Multi-Epitope Vaccine Based on Urate Transporter 1 Alleviates
      Streptozotocin-Induced Diabetes by Producing Anti-URAT1 Antibody and an
      Immunomodulatory Effect in C57BL/6J Mice.
AB  - Hyperuricemia (HUA) is related to diabetes. Uric acid-induced inflammation and
      oxidative stress are risk factors for diabetes and its complications. Human urate
      transporter 1 (URAT1) regulates the renal tubular reabsorption of uric acid. IA
      2(5)-P2-1, a potent immunogenic carrier designed by our laboratory, can induce
      high-titer specific antibodies when it carries a B cell epitope, such as B cell
      epitopes of DPP4 (Dipeptidyl peptidase-4), xanthine oxidase. In this report, we
      describe a novel multi-epitope vaccine composing a peptide of URAT1, an anti
      diabetic B epitope of insulinoma antigen-2(IA-2) and a Th2 epitope
      (P2:IPALDSLTPANED) of P277 peptide in human heat shock protein 60 (HSP60).
      Immunization with the multi-epitope vaccine in streptozotocin-induced diabetes
      C57BL/6J mice successfully induced specific anti-URAT1 antibody, which inhibited
      URAT1 action and uric acid reabsorption, and increased pancreatic insulin level
      with a lower insulitis incidence. Vaccination with U-IA-2(5)-P2-1 (UIP-1)
      significantly reduced blood glucose and uric acid level, increased Th2 cytokines
      interleukin (IL)-10 and IL-4, and regulated immune reactions through a balanced
      Th1/Th2 ratio. These results demonstrate that the URAT1-based multi-epitope
      peptide vaccine may be a suitable therapeutic approach for diabetes and its
      complications.

PMID- 29035323
TI  - Hypothalamic-Pituitary-Adrenal Axis Modulation of Glucocorticoids in the
      Cardiovascular System.
AB  - The collective of endocrine organs acting in homeostatic regulation-known as the
      hypothalamic-pituitary-adrenal (HPA) axis-comprises an integration of the central
      nervous system as well as peripheral tissues. These organs respond to imminent or
      perceived threats that elicit a stress response, primarily culminating in the
      release of glucocorticoids into the systemic circulation by the adrenal glands.
      Although the secretion of glucocorticoids serves to protect and maintain
      homeostasis in the typical operation at baseline levels, inadequate regulation
      can lead to physiologic and psychologic pathologies. The cardiovascular system is
      especially susceptible to prolonged dysregulation of the HPA axis and
      glucocorticoid production. There is debate about whether cardiovascular health
      risks arise from the direct detrimental effects of stress axis activation or
      whether pathologies develop secondary to the accompanying metabolic strain of
      excess glucocorticoids. In this review, we will explore the emerging research
      that indicates stress does have direct effects on the cardiovascular system via
      the HPA axis activation, with emphasis on the latest research on the impact of
      glucocorticoids signaling in the vasculature and the heart.

PMID- 29035326
TI  - Prebiotic RNA Network Formation: A Taxonomy of Molecular Cooperation.
AB  - Cooperation is essential for evolution of biological complexity. Recent work has
      shown game theoretic arguments, commonly used to model biological cooperation,
      can also illuminate the dynamics of chemical systems. Here we investigate the
      types of cooperation possible in a real RNA system based on the Azoarcus
      ribozyme, by constructing a taxonomy of possible cooperative groups. We construct
      a computational model of this system to investigate the features of the real
      system promoting cooperation. We find triplet interactions among genotypes are
      intrinsically biased towards cooperation due to the particular distribution of
      catalytic rate constants measured empirically in the real system. For other
      distributions cooperation is less favored. We discuss implications for
      understanding cooperation as a driver of complexification in the origin of life.

PMID- 29035325
TI  - Advanced Prodrug Strategies in Nucleoside and Non-Nucleoside Antiviral Agents: A
      Review of the Recent Five Years.
AB  - Background: Poor pharmacokinetic profiles and resistance are the main two
      drawbacks from which currently used antiviral agents suffer, thus make them
      excellent targets for research, especially in the presence of viral pandemics
      such as HIV and hepatitis C. Methods: The strategies employed in the studies
      covered in this review were sorted by the type of drug synthesized into ester
      prodrugs, targeted delivery prodrugs, macromolecular prodrugs, other nucleoside
      conjugates, and non-nucleoside drugs. Results: Utilizing the ester prodrug
      approach a novel isopropyl ester prodrug was found to be potent HIV integrase
      inhibitor. Further, employing the targeted delivery prodrug zanamivir and valine
      ester prodrug was made and shown a sole delivery of zanamivir. Additionally,
      VivaGel, a dendrimer macromolecular prodrug, was found to be very efficient and
      is now undergoing clinical trials. Conclusions: Of all the strategies employed
      (ester, targeted delivery, macromolecular, protides and nucleoside analogues, and
      non-nucleoside analogues prodrugs), the most promising are nucleoside analogues
      and macromolecular prodrugs. The macromolecular prodrug VivaGel works by two
      mechanisms: envelope mediated and receptor mediated disruption. Nucleotide
      analogues have witnessed productive era in the recent past few years. The era of
      non-interferon based treatment of hepatitis (through direct inhibitors of NS5A)
      has dawned.

PMID- 29035327
TI  - Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne
      Muscular Dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a lethal genetic disorder that most commonly
      results from mutations disrupting the reading frame of the dystrophin (DMD) gene.
      Among the therapeutic approaches employed, exon skipping using antisense
      oligonucleotides (AOs) is one of the most promising strategies. This strategy
      aims to restore the reading frame, thus producing a truncated, yet functioning
      dystrophin protein. In 2016, the Food and Drug Administration (FDA) conditionally
      approved the first AO-based drug, eteplirsen (Exondys 51), developed for DMD exon
      51 skipping. An accurate and reproducible method to quantify exon skipping
      efficacy is essential for evaluating the therapeutic potential of different AOs
      sequences. However, previous in vitro screening studies have been hampered by the
      limited proliferative capacity and insufficient amounts of dystrophin expressed
      by primary muscle cell lines that have been the main system used to evaluate AOs
      sequences. In this paper, we illustrate the challenges associated with primary
      muscle cell lines and describe a novel approach that utilizes immortalized cell
      lines to quantitatively evaluate the exon skipping efficacy in in vitro studies.

PMID- 29035328
TI  - Pterodontic Acid Isolated from Laggera pterodonta Inhibits Viral Replication and
      Inflammation Induced by Influenza A Virus.
AB  - Laggera pterodonta (DC.) Benth. is a traditional Chinese medicine. The previous
      study revealed that the crude extracts of this herb could inhibit influenza virus
      infection, but its anti-influenza components and underlying mechanism of action
      remain unknown. Column chromatography was performed to isolate components from
      the plant. Activity against influenza virus of the compound was determined by CPE
      inhibition assay. Neuraminidase (NA) inhibition was measured by chemiluminescence
      assay. The anti-virus and anti-inflammation effects were determined using dual
      luciferase reporter assay, immunofluorescence, quantitative real-time PCR and
      luminex assay. Pterodontic acid was isolated from L. pterodonta, which showed
      selective anti-viral activities to H1 subtype of human influenza A virus.
      Meanwhile, the NA activity was not obviously inhibited by the compound. Further
      experiments exhibited that the compound can suppress the activation of NF-kappaB
      signal pathway and export of viral RNP complexes from the nucleus. In addition,
      it can significantly attenuate expression of the pro-inflammatory molecules IL-6,
      MIP-1beta, MCP-1, and IP-10 induced by human influenza A virus (H1N1) and
      similarly downregulate expression of cytokines and chemokines induced by avian
      influenza A virus (H9N2). This study showed that in vitro antiviral activity of
      pterodontic acid is most probably associated with inhibiting the replication of
      influenza A virus by blocking nuclear export of viral RNP complexes, and
      attenuating the inflammatory response by inhibiting activation of the NF-kappaB
      pathway. Pterodontic acid might be a potential antiviral agent against influenza
      A virus.

PMID- 29035329
TI  - Camera Calibration Robust to Defocus Using Phase-Shifting Patterns.
AB  - Camera parameters can't be estimated accurately using traditional calibration
      methods if the camera is substantially defocused. To tackle this problem, an
      improved approach based on three phase-shifting circular grating (PCG) arrays is
      proposed in this paper. Rather than encoding the feature points into the
      intensity, the proposed method encodes the feature points into the phase
      distribution, which can be recovered precisely using phase-shifting methods. The
      PCG centers are extracted as feature points, which can be located accurately even
      if the images are severely blurred. Unlike the previous method which just uses a
      single circle, the proposed method uses a concentric circle to estimate the PCG
      center, such that the center can be located precisely. This paper also presents a
      sorting algorithm for the detected feature points automatically. Experiments with
      both synthetic and real images were carried out to validate the performance of
      the method. And the results show that the superiority of PCG arrays compared with
      the concentric circle array even under severe defocus.

PMID- 29035330
TI  - Whites but Not Blacks Gain Life Expectancy from Social Contacts.
AB  - Background. Recent research suggests that the health gain from economic resources
      and psychological assets may be systematically larger for Whites than Blacks.
      Aim. This study aimed to assess whether the life expectancy gain associated with
      social contacts over a long follow up differs for Blacks and Whites. Methods.
      Data came from the Americans' Changing Lives (ACL) Study, 1986-2011. The sample
      was a nationally representative sample of American adults 25 and older, who were
      followed for up to 25 years (n = 3361). Outcome was all-cause mortality. The main
      predictor was social contacts defined as number of regular visits with friends,
      relatives, and neighbors. Baseline demographics (age and gender), socioeconomic
      status (education, income, and employment), health behaviors (smoking and
      drinking), and health (chronic medical conditions, obesity, and depressive
      symptoms) were controlled. Race was the focal moderator. Cox proportional hazard
      models were used in the pooled sample and based on race. Results. More social
      contacts predicted higher life expectancy in the pooled sample. A significant
      interaction was found between race and social contacts, suggesting that the
      protective effect of more social contacts is smaller for Blacks than Whites. In
      stratified models, more social contacts predicted an increased life expectancy
      for Whites but not Blacks. Conclusion. Social contacts increase life expectancy
      for White but not Black Americans. This study introduces social contacts as
      another social resource that differentially affects health of Whites and Blacks.

PMID- 29035332
TI  - Random Network Models to Predict the Long-Term Impact of HPV Vaccination on
      Genital Warts.
AB  - The Human papillomaviruses (HPV) vaccine induces a herd immunity effect in
      genital warts when a large number of the population is vaccinated. This aspect
      should be taken into account when devising new vaccine strategies, like
      vaccination at older ages or male vaccination. Therefore, it is important to
      develop mathematical models with good predictive capacities. We devised a sexual
      contact network that was calibrated to simulate the Spanish epidemiology of
      different HPV genotypes. Through this model, we simulated the scenario that
      occurred in Australia in 2007, where 12-13 year-old girls were vaccinated with a
      three-dose schedule of a vaccine containing genotypes 6 and 11, which protect
      against genital warts, and also a catch-up program in women up to 26 years of
      age. Vaccine coverage were 73 % in girls with three doses and with coverage rates
      decreasing with age until 52 % for 20-26 year-olds. A fast 59 % reduction in the
      genital warts diagnoses occurred in the model in the first years after the start
      of the program, similar to what was described in the literature.

PMID- 29035333
TI  - Water Quality Sensing and Spatio-Temporal Monitoring Structure with
      Autocorrelation Kernel Methods.
AB  - Pollution on water resources is usually analyzed with monitoring campaigns, which
      consist of programmed sampling, measurement, and recording of the most
      representative water quality parameters. These campaign measurements yields a non
      uniform spatio-temporal sampled data structure to characterize complex dynamics
      phenomena. In this work, we propose an enhanced statistical interpolation method
      to provide water quality managers with statistically interpolated representations
      of spatial-temporal dynamics. Specifically, our proposal makes efficient use of
      the a priori available information of the quality parameter measurements through
      Support Vector Regression (SVR) based on Mercer's kernels. The methods are
      benchmarked against previously proposed methods in three segments of the
      Machangara River and one segment of the San Pedro River in Ecuador, and their
      different dynamics are shown by statistically interpolated spatial-temporal maps.
      The best interpolation performance in terms of mean absolute error was the SVR
      with Mercer's kernel given by either the Mahalanobis spatial-temporal covariance
      matrix or by the bivariate estimated autocorrelation function. In particular, the
      autocorrelation kernel provides with significant improvement of the estimation
      quality, consistently for all the six water quality variables, which points out
      the relevance of including a priori knowledge of the problem.

PMID- 29035334
TI  - A Low Cost Sensors Approach for Accurate Vehicle Localization and Autonomous
      Driving Application.
AB  - Autonomous driving in public roads requires precise localization within the range
      of few centimeters. Even the best current precise localization system based on
      the Global Navigation Satellite System (GNSS) can not always reach this level of
      precision, especially in an urban environment, where the signal is disturbed by
      surrounding buildings and artifacts. Laser range finder and stereo vision have
      been successfully used for obstacle detection, mapping and localization to solve
      the autonomous driving problem. Unfortunately, Light Detection and Ranging
      (LIDARs) are very expensive sensors and stereo vision requires powerful dedicated
      hardware to process the cameras information. In this context, this article
      presents a low-cost architecture of sensors and data fusion algorithm capable of
      autonomous driving in narrow two-way roads. Our approach exploits a combination
      of a short-range visual lane marking detector and a dead reckoning system to
      build a long and precise perception of the lane markings in the vehicle's
      backwards. This information is used to localize the vehicle in a map, that also
      contains the reference trajectory for autonomous driving. Experimental results
      show the successful application of the proposed system on a real autonomous
      driving situation.

PMID- 29035331
TI  - Nutritional Needs and Support for Children with Chronic Liver Disease.
AB  - Malnutrition has become a dangerously common problem in children with chronic
      liver disease, negatively impacting neurocognitive development and growth.
      Furthermore, many children with chronic liver disease will eventually require
      liver transplantation. Thus, this association between malnourishment and chronic
      liver disease in children becomes increasingly alarming as malnutrition is a
      predictor of poorer outcomes in liver transplantation and is often associated
      with increased morbidity and mortality. Malnutrition requires aggressive and
      appropriate management to correct nutritional deficiencies. A comprehensive
      review of the literature has found that infants with chronic liver disease (CLD)
      are particularly susceptible to malnutrition given their low reserves. Children
      with CLD would benefit from early intervention by a multi-disciplinary team, to
      try to achieve nutritional rehabilitation as well as to optimize outcomes for
      liver transplant. This review explains the multifactorial nature of malnutrition
      in children with chronic liver disease, defines the nutritional needs of these
      children, and discusses ways to optimize their nutritional.

PMID- 29035335
TI  - Selectivity Enhancement in Electronic Nose Based on an Optimized DQN.
AB  - In order to enhance the selectivity of metal oxide gas sensors, we use a flow
      modulation method to exploit transient sensor information. The method is based on
      modulating the flow of the carrier gas that brings the species to be measured
      into the sensor chamber. We present an active perception strategy by using a DQN
      which can optimize the flow modulation online. The advantage of DQN is not only
      that the classification accuracy is higher than traditional methods such as PCA,
      but also that it has a good adaptability under small samples and labeled data.
      From observed values of the sensors array and its past experiences, the DQN
      learns an action policy to change the flow speed dynamically that maximizes the
      total rewards (or minimizes the classification error). Meanwhile, a CNN is
      trained to predict sample class and reward according to current actions and
      observation of sensors. We demonstrate our proposed methods on a gases
      classification problem in a real time environment. The results show that the DQN
      learns to modulate flow to classify different gas and the correct rates of gases
      are: sesame oil 100%, lactic acid 80%, acetaldehyde 80%, acetic acid 80%, and
      ethyl acetate 100%, the average correct rate is 88%. Compared with the
      traditional method, the results of PCA are: sesame oil 100%, acetic acid 24%,
      acetaldehyde 100%, lactic acid 56%, ethyl acetate 68%, the average accuracy rate
      is 69.6%. DQN uses fewer steps to achieve higher recognition accuracy and improve
      the recognition speed, and to reduce the training and testing costs.

PMID- 29035336
TI  - Transition of Emission Colours as a Consequence of Heat-Treatment of Carbon
      Coated Ce3+-Doped YAG Phosphors.
AB  - To modify the luminescence properties of Ce3+-doped Y3Al5O12 (YAG) phosphors,
      they have been coated with a carbon layer by chemical vapor deposition and
      subsequently heat-treated at high temperature under N2 atmosphere. Luminescence
      of the carbon coated YAG:Ce3+ phosphors has been investigated as a function of
      heat-treatment at 1500 and 1650  degrees C. The 540 nm emission intensity of
      C@YAG:Ce3+ is the highest when heated at 1650  degrees C, while a blue emission
      at 400-420 nm is observed when heated at 1500  degrees C but not at 1650  degrees
      C. It is verified by X-ray diffraction (XRD) that the intriguing luminescence
      changes are induced by the formation of new phases in C@YAG:Ce3+-1500  degrees C,
      which disappear in C@YAG:Ce3+-1650  degrees C. In order to understand the
      mechanisms responsible for the enhancement of YAG:Ce3+ emission and the presence
      of the blue emission observed for C@YAG:Ce3+-1500  degrees C, the samples have
      been investigated by a combination of several electron microscopy techniques,
      such as HRTEM, SEM-CL, and SEM-EDS. This local and cross-sectional analysis
      clearly reveals a gradual transformation of phase and morphology in heated
      C@YAG:Ce3+ phosphors, which is related to a reaction between C and YAG:Ce3+ in N2
      atmosphere. Through reaction between the carbon layer and YAG host materials, the
      emission colour of the phosphors can be modified from yellow, white, and then
      back to yellow under UV excitation as a function of heat-treatment in N2
      atmosphere.

PMID- 29035337
TI  - Role of Information Anxiety and Information Load on Processing of Prescription
      Drug Information Leaflets.
AB  - In this study, we evaluate the role of information anxiety and information load
      on the intention to read information from prescription drug information leaflets
      (PILs). These PILs were developed based on the principals of information load and
      consumer information processing. This was an experimental prospective repeated
      measures study conducted in the United States where 360 (62% response rate)
      university students (>18 years old) participated. Participants were presented
      with a scenario followed by exposure to the three drug product information
      sources used to operationalize information load. The three sources were: (i)
      current practice; (ii) pre-existing one-page text only; and (iii) interventional
      one-page prototype PILs designed for the study. Information anxiety was measured
      as anxiety experienced by the individual when encountering information. The
      outcome variable of intention to read PILs was defined as the likelihood that the
      patient will read the information provided in the leaflets. A survey
      questionnaire was used to capture the data and the objectives were analyzed by
      performing a repeated measures MANOVA using SAS version 9.3. When compared to
      current practice and one-page text only leaflets, one-page PILs had significantly
      lower scores on information anxiety (p < 0.001) and information load (p < 0.001).
      The intention to read was highest and significantly different (p < 0.001) for
      PILs as compared to current practice or text only leaflets. Information anxiety
      and information load significantly impacted intention to read (p < 0.001). Newly
      developed PILs increased patient's intention to read and can help in improving
      the counseling services provided by pharmacists.

PMID- 29035338
TI  - Integrating Medication Therapy Management (MTM) Services Provided by Community
      Pharmacists into a Community-Based Accountable Care Organization (ACO).
AB  - (1) Background: As the U.S. healthcare system evolves from fee-for-service
      financing to global population-based payments designed to be accountable for both
      quality and total cost of care, the effective and safe use of medications is
      gaining increased importance. The purpose of this project was to determine the
      feasibility of integrating medication therapy management (MTM) services provided
      by community pharmacists into the clinical care teams and the health information
      technology (HIT) infrastructure for Minnesota Medicaid recipients of a 12-county
      community-based accountable care organization (ACO). (2) Methods: The continuous
      quality improvement evaluation methodology employed in this project was the
      context + mechanism = outcome (CMO) model to account for the fact that programs
      only work insofar as they introduce promising ideas, solutions and opportunities
      in the appropriate social and cultural contexts. Collaborations between a 12
      county ACO and 15 community pharmacies in Southwest Minnesota served as the
      social context for this feasibility study of MTM referrals to community
      pharmacists. (3) Results: All 15 community pharmacy sites were integrated into
      the HIT infrastructure through Direct Secure Messaging, and there were 32
      recipients who received MTM services subsequent to referrals from the ACO at 5 of
      the 15 community pharmacies over a 1-year implementation phase. (4) Conclusion:
      At the conclusion of this project, an effective electronic communication and MTM
      referral system was activated, and consideration was given to community
      pharmacists providing MTM in future ACO shared savings agreements.

PMID- 29035339
TI  - Promoting Effect of Pinostrobin on the Proliferation, Differentiation, and
      Mineralization of Murine Pre-osteoblastic MC3T3-E1 Cells.
AB  - Pinostrobin (PI), a natural flavonoid found in a variety of plants, is well known
      for its rich pharmacological activities. However, its osteogenic function remains
      unclear. The aim of this study is to evaluate the effect of PI on the
      proliferation, differentiation, and mineralization of murine pre-osteoblastic
      MC3T3-E1 cells in vitro using MTT, alkaline phosphatase (ALP) activity, the
      synthesis of collagen I (Col I) assay, and Von-Kossa staining, respectively. The
      expression of osteocalcin (OCN) mRNA in cells was detected by real-time PCR. The
      effect of PI on the differentiation of dexamethasone (DEX)-suppressed cells was
      also investigated. The results showed that PI greatly promoted the proliferation
      of MC3T3-E1 cells at 5-80 MUg/mL (p < 0.05 or p < 0.01), and caused a significant
      elevation of ALP activity, Col I content, and mineralization of osteoblasts at 10
      40 MUg/mL (p < 0.05 or p < 0.01), and the expression levels of OCN gene were
      greatly upregulated after PI treatment (p < 0.01). Furthermore, PI could rescue
      the inhibition effect of cell differentiation induced by DEX. Taken together,
      these results indicated that PI could directly promote proliferation,
      differentiation, and mineralization of MC3T3-E1 cells and has potential for use
      as a natural treatment for osteoporosis.

PMID- 29035340
TI  - Special Issue: Improvements for Resveratrol Efficacy.
AB  - Resveratrol is a well-known phenolic stilbene because of its presence in several
      edible plants and its proposed properties that are beneficial to human health
      [...].

PMID- 29035341
TI  - Research on the Fusion of Dependent Evidence Based on Rank Correlation
      Coefficient.
AB  - In order to meet the higher accuracy and system reliability requirements, the
      information fusion for multi-sensor systems is an increasing concern. Dempster
      Shafer evidence theory (D-S theory) has been investigated for many applications
      in multi-sensor information fusion due to its flexibility in uncertainty
      modeling. However, classical evidence theory assumes that the evidence is
      independent of each other, which is often unrealistic. Ignoring the relationship
      between the evidence may lead to unreasonable fusion results, and even lead to
      wrong decisions. This assumption severely prevents D-S evidence theory from
      practical application and further development. In this paper, an innovative
      evidence fusion model to deal with dependent evidence based on rank correlation
      coefficient is proposed. The model first uses rank correlation coefficient to
      measure the dependence degree between different evidence. Then, total discount
      coefficient is obtained based on the dependence degree, which also considers the
      impact of the reliability of evidence. Finally, the discount evidence fusion
      model is presented. An example is illustrated to show the use and effectiveness
      of the proposed method.

PMID- 29035342
TI  - Seed Transmission of Beet Curly Top Virus and Beet Curly Top Iran Virus in a
      Local Cultivar of Petunia in Iran.
AB  - Beet curly top virus (BCTV) and beet curly top Iran virus (BCTIV) are known as
      the causal agents of curly top disease in beet and several other dicotyledonous
      plants in Iran. These viruses are transmitted by Circulifer species, and until
      now, there has been no confirmed report of their seed transmission. A percentage
      (38.2-78.0%) of the seedlings developed from the seeds of a petunia local
      cultivar under insect-free conditions showed stunting, interveinal chlorosis,
      leaf curling, and vein swelling symptoms, and were infected by BCTV when tested
      by PCR. Presence of BCTV in seed extracts of petunia local cultivar was confirmed
      by PCR and IC-PCR, followed by sequencing. Agroinoculation of curly top free
      petunia plants with a BCTV infectious clone resulted in BCTV infection of plants
      and their developed seeds. These results show the seed infection and transmission
      of BCTV in a local cultivar of petunia. Similar experiments performed with BCTIV
      showed that this virus is also seed transmissible in the same cultivar of
      petunia, although with a lower rate (8.8-18.5%). Seed transmission of curly top
      viruses may have significant implications in the epidemiology of these viruses.

PMID- 29035343
TI  - A Highly Selective and Sensitive Fluorescent Turn-Off Probe for Cu2+ Based on a
      Guanidine Derivative.
AB  - A new highly selective and sensitive fluorescent probe for Cu2+, N-n-butyl-4-(1'
      cyclooctene-1',3',6'-triazole)-1,8-naphthalimide (L), was synthesized and
      evaluated. The structure of compound L was characterized via IR, 1H-NMR, 13C-NMR
      and HRMS. The fluorescent probe was quenched by Cu2+ with a 1:1 binding ratio and
      behaved as a "turn-off" sensor. An efficient and sensitive spectrofluorometric
      method was developed for detecting and estimating trace levels of Cu2+ in
      EtOH/H2O. The ligand exhibited excitation and emission maxima at 447 and 518 nm,
      respectively. The equilibrium binding constant of the ligand with Cu2+ was 1.57 *
      104 M-1, as calculated using the Stern.

PMID- 29035344
TI  - A Phase-Intensity Surface Plasmon Resonance Biosensor for Avian Influenza A
      (H5N1) Detection.
AB  - In this paper, we present a phase-intensity surface plasmon resonance (SPR)
      biosensor and demonstrate its use for avian influenza A (H5N1) antibody biomarker
      detection. The sensor probes the intensity variation produced by the steep phase
      response at surface plasmon excitation. The prism sensor head is fixed between a
      pair of polarizers with a perpendicular orientation angle and a forbidden
      transmission path. At SPR, a steep phase change is introduced between the p- and
      s-polarized light, and this rotates the polarization ellipse of the transmission
      beam. This allows the light at resonance to be transmitted and a corresponding
      intensity change to be detected. Neither time-consuming interference fringe
      analysis nor a phase extraction process is required. In refractive index sensing
      experiments, the sensor resolution was determined to be 6.3 * 10-6 refractive
      index values (RIU). The sensor has been further applied for H5N1 antibody
      biomarker detection, and the sensor resolution was determined to be 193.3 ng mL
      1, compared to 1 MUg mL-1 and 0.5 MUg mL-1, as reported in literature for
      influenza antibody detection using commercial Biacore systems. It represents a
      517.3% and 258.7% improvement in detection limit, respectively. With the unique
      features of label-free, real-time, and sensitive detection, the phase-intensity
      SPR biosensor has promising potential applications in influenza detection.

PMID- 29035345
TI  - An Improved Scheduling Algorithm for Data Transmission in Ultrasonic Phased
      Arrays with Multi-Group Ultrasonic Sensors.
AB  - High data transmission efficiency is a key requirement for an ultrasonic phased
      array with multi-group ultrasonic sensors. Here, a novel FIFOs scheduling
      algorithm was proposed and the data transmission efficiency with hardware
      technology was improved. This algorithm includes FIFOs as caches for the
      ultrasonic scanning data obtained from the sensors with the output data in a
      bandwidth-sharing way, on the basis of which an optimal length ratio of all the
      FIFOs is achieved, allowing the reading operations to be switched among all the
      FIFOs without time slot waiting. Therefore, this algorithm enhances the
      utilization ratio of the reading bandwidth resources so as to obtain higher
      efficiency than the traditional scheduling algorithms. The reliability and
      validity of the algorithm are substantiated after its implementation in the field
      programmable gate array (FPGA) technology, and the bandwidth utilization ratio
      and the real-time performance of the ultrasonic phased array are enhanced.

PMID- 29035347
TI  - Modeling the Energy Performance of LoRaWAN.
AB  - LoRaWAN is a flagship Low-Power Wide Area Network (LPWAN) technology that has
      highly attracted much attention from the community in recent years. Many LoRaWAN
      end-devices, such as sensors or actuators, are expected not to be powered by the
      electricity grid; therefore, it is crucial to investigate the energy consumption
      of LoRaWAN. However, published works have only focused on this topic to a limited
      extent. In this paper, we present analytical models that allow the
      characterization of LoRaWAN end-device current consumption, lifetime and energy
      cost of data delivery. The models, which have been derived based on measurements
      on a currently prevalent LoRaWAN hardware platform, allow us to quantify the
      impact of relevant physical and Medium Access Control (MAC) layer LoRaWAN
      parameters and mechanisms, as well as Bit Error Rate (BER) and collisions, on
      energy performance. Among others, evaluation results show that an appropriately
      configured LoRaWAN end-device platform powered by a battery of 2400 mAh can
      achieve a 1-year lifetime while sending one message every 5 min, and an
      asymptotic theoretical lifetime of 6 years for infrequent communication.

PMID- 29035348
TI  - Air-Coupled Ultrasonic Receivers with High Electromechanical Coupling PMN-32%PT
      Strip-Like Piezoelectric Elements.
AB  - For improvement of the efficiency of air-coupled ultrasonic transducers PMN-32%PT
      piezoelectric crystals which possess very high piezoelectric properties may be
      used. The electromechanical coupling factor of such crystals for all main
      vibration modes such as the thickness extension and transverse extension modes is
      more than 0.9. Operation of ultrasonic transducers with such piezoelectric
      elements in transmitting and receiving modes is rather different. Therefore, for
      transmission and reception of ultrasonic signals, separate piezoelectric elements
      with different dimensions must be used. The objective of this research was
      development of novel air-coupled ultrasonic receivers with PMN-32%PT strip-like
      piezoelectric elements vibrating in a transverse-extension mode with
      electromechanically controlled operation and suitable for applications in
      ultrasonic arrays. Performance of piezoelectric receivers made of the PMN-32%PT
      strip-like elements vibrating in this mode may be efficiently controlled by
      selecting geometry of the electrodes covering side surfaces of the piezoelectric
      element. It is equivalent to introduction of electromechanical damping which does
      not require any additional backing element. For this purpose; we have proposed
      the continuous electrodes to divide into two pairs of electrodes. The one pair is
      used to pick up the electric signal; another one is exploited for
      electromechanical damping. Two types of electrodes may be used-rectangular or non
      rectangular-with a gap between them directed at some angle, usually 45 degrees .
      The frequency bandwidth is wider (up to 9 kHz) in the case of non-rectangular
      electrodes. The strip-like acoustic matching element bonded to the tip of the PMN
      32%PT crystal may significantly enhance the performance of the ultrasonic
      receiver. It was proposed to use for this purpose AIREX T10.110 rigid polymer
      foam, the acoustic impedance of which is close to the optimal value necessary for
      matching with air. It was found that in order to get a wide bandwidth the length
      of the matching strip should be selected not a quarter wavelength lambda/4 at the
      antiresonance frequency but at lower frequency. It allowed achieving the
      frequency bandwidth (14-18)% with respect to the central frequency at -3 dB
      level.

PMID- 29035349
TI  - Design of Research on Performance of a New Iridium Coordination Compound for the
      Detection of Hg2.
AB  - Heavy metal pollution has become one of the most significant pollution problems
      encountered by our country in terms of environment protection. In addition to the
      significant effects of heavy metals on the human body and other organisms through
      water, food chain enrichment and other routes, heavy metals involved in daily
      necessities beyond the level limit could also affect people's lives, so the
      detection of heavy metals is extremely important. Ir (III) coordination compound,
      considered to be one of the best phosphorescent sensing materials, is
      characterized by high luminous efficiency, easy modification of the ligand and so
      on, and it has potential applications in the field of heavy metal detection. This
      project aims to product a new Ir (III) functional coordination compound by
      designing a new auxiliary ligand and a main ligand with a sulfur identification
      unit, in order to systematically investigate the application of iridium
      coordination compound in the detection of the heavy metal Hg2+. With the
      introduction of the sulfur identification unit, selective sensing of Hg2+ could
      be achieved. Additionally, a new auxiliary ligand is also introduced to produce a
      functional iridium coordination compound with high quantum efficiency, and to
      diversify the application of iridium coordination compound in this field.

PMID- 29035346
TI  - Redox Signaling and Its Impact on Skeletal and Vascular Responses to Spaceflight.
AB  - Spaceflight entails exposure to numerous environmental challenges with the
      potential to contribute to both musculoskeletal and vascular dysfunction. The
      purpose of this review is to describe current understanding of microgravity and
      radiation impacts on the mammalian skeleton and associated vasculature at the
      level of the whole organism. Recent experiments from spaceflight and ground-based
      models have provided fresh insights into how these environmental stresses
      influence mechanisms that are related to redox signaling, oxidative stress, and
      tissue dysfunction. Emerging mechanistic knowledge on cellular defenses to
      radiation and other environmental stressors, including microgravity, are useful
      for both screening and developing interventions against spaceflight-induced
      deficits in bone and vascular function.

PMID- 29035350
TI  - Asymmetric Dual-Band Tracking Technique for Optimal Joint Processing of BDS B1I
      and B1C Signals.
AB  - Along with the rapid development of the Global Navigation Satellite System
      (GNSS), satellite navigation signals have become more diversified, complex, and
      agile in adapting to increasing market demands. Various techniques have been
      developed for processing multiple navigation signals to achieve better
      performance in terms of accuracy, sensitivity, and robustness. This paper focuses
      on a technique for processing two signals with separate but adjacent center
      frequencies, such as B1I and B1C signals in the BeiDou global system. The two
      signals may differ in modulation scheme, power, and initial phase relation and
      can be processed independently by user receivers; however, the propagation delays
      of the two signals from a satellite are nearly identical as they are modulated on
      adjacent frequencies, share the same reference clock, and undergo nearly
      identical propagation paths to the receiver, resulting in strong coherence
      between the two signals. Joint processing of these signals can achieve optimal
      measurement performance due to the increased Gabor bandwidth and power. In this
      paper, we propose a universal scheme of asymmetric dual-band tracking (ASYM-DBT)
      to take advantage of the strong coherence, the increased Gabor bandwidth, and
      power of the two signals in achieving much-reduced thermal noise and more
      accurate ranging results when compared with the traditional single-band
      algorithm.

PMID- 29035353
TI  - Liquid metal-organic frameworks.
AB  - Metal-organic frameworks (MOFs) are a family of chemically diverse materials,
      with applications in a wide range of fields, covering engineering, physics,
      chemistry, biology and medicine. Until recently, research has focused almost
      entirely on crystalline structures, yet now a clear trend is emerging, shifting
      the emphasis onto disordered states, including 'defective by design' crystals, as
      well as amorphous phases such as glasses and gels. Here we introduce a strongly
      associated MOF liquid, obtained by melting a zeolitic imidazolate framework. We
      combine in situ variable temperature X-ray, ex situ neutron pair distribution
      function experiments, and first-principles molecular dynamics simulations to
      study the melting phenomenon and the nature of the liquid obtained. We
      demonstrate from structural, dynamical, and thermodynamical information that the
      chemical configuration, coordinative bonding, and porosity of the parent
      crystalline framework survive upon formation of the MOF liquid.

PMID- 29035352
TI  - Erratum: USP11 regulates PML stability to control Notch-induced malignancy in
      brain tumours.
AB  - This corrects the article DOI: 10.1038/ncomms4214.

PMID- 29035354
TI  - Liquid porous materials: Unveiling liquid MOFs.

PMID- 29035351
TI  - Rebalancing beta-Amyloid-Induced Decrease of ATP Level by Amorphous Nano/Micro
      Polyphosphate: Suppression of the Neurotoxic Effect of Amyloid beta-Protein
      Fragment 25-35.
AB  - Morbus Alzheimer neuropathology is characterized by an impaired energy
      homeostasis of brain tissue. We present an approach towards a potential therapy
      of Alzheimer disease based on the high-energy polymer inorganic polyphosphate
      (polyP), which physiologically occurs both in the extracellular and in the
      intracellular space. Rat pheochromocytoma (PC) 12 cells, as well as rat primary
      cortical neurons were exposed to the Alzheimer peptide Abeta25-35. They were
      incubated in vitro with polyphosphate (polyP); ortho-phosphate was used as a
      control. The polymer remained as Na+ salt; or complexed in a stoichiometric ratio
      to Ca2+ (Na-polyP[Ca2+]); or was processed as amorphous Ca-polyP microparticles
      (Ca-polyP-MP). Ortho-phosphate was fabricated as crystalline Ca-phosphate
      nanoparticles (Ca-phosphate-NP). We show that the pre-incubation of PC12 cells
      and primary cortical neurons with polyP protects the cells against the neurotoxic
      effect of the Alzheimer peptide Abeta25-35. The strongest effect was observed
      with amorphous polyP microparticles (Ca-polyP-MP). The effect of the soluble
      sodium salt; Na-polyP (Na-polyP[Ca2+]) was lower; while crystalline
      orthophosphate nanoparticles (Ca-phosphate-NP) were ineffective. Ca-polyP-MP
      microparticles and Na-polyP[Ca2+] were found to markedly enhance the
      intracellular ATP level. Pre-incubation of Abeta25-35 during aggregate formation,
      with the polyP preparation before exposure of the cells, had a small effect on
      neurotoxicity. We conclude that recovery of the compromised energy status in
      neuronal cells by administration of nontoxic biodegradable Ca-salts of polyP
      reverse the beta-amyloid-induced decrease of adenosine triphosphate (ATP) level.
      This study contributes to a new routes for a potential therapeutic intervention
      in Alzheimer's disease pathophysiology.

PMID- 29035356
TI  - Circulating tumour DNA methylation markers for diagnosis and prognosis of
      hepatocellular carcinoma.
AB  - An effective blood-based method for the diagnosis and prognosis of hepatocellular
      carcinoma (HCC) has not yet been developed. Circulating tumour DNA (ctDNA)
      carrying cancer-specific genetic and epigenetic aberrations may enable a
      noninvasive 'liquid biopsy' for diagnosis and monitoring of cancer. Here, we
      identified an HCC-specific methylation marker panel by comparing HCC tissue and
      normal blood leukocytes and showed that methylation profiles of HCC tumour DNA
      and matched plasma ctDNA are highly correlated. Using cfDNA samples from a large
      cohort of 1,098 HCC patients and 835 normal controls, we constructed a diagnostic
      prediction model that showed high diagnostic specificity and sensitivity (P <
      0.001) and was highly correlated with tumour burden, treatment response, and
      stage. Additionally, we constructed a prognostic prediction model that
      effectively predicted prognosis and survival (P < 0.001). Together, these
      findings demonstrate in a large clinical cohort the utility of ctDNA methylation
      markers in the diagnosis, surveillance, and prognosis of HCC.

PMID- 29035355
TI  - Sequential bottom-up assembly of mechanically stabilized synthetic cells by
      microfluidics.
AB  - Compartments for the spatially and temporally controlled assembly of biological
      processes are essential towards cellular life. Synthetic mimics of cellular
      compartments based on lipid-based protocells lack the mechanical and chemical
      stability to allow their manipulation into a complex and fully functional
      synthetic cell. Here, we present a high-throughput microfluidic method to
      generate stable, defined sized liposomes termed 'droplet-stabilized giant
      unilamellar vesicles (dsGUVs)'. The enhanced stability of dsGUVs enables the
      sequential loading of these compartments with biomolecules, namely purified
      transmembrane and cytoskeleton proteins by microfluidic pico-injection
      technology. This constitutes an experimental demonstration of a successful bottom
      up assembly of a compartment with contents that would not self-assemble to full
      functionality when simply mixed together. Following assembly, the stabilizing oil
      phase and droplet shells are removed to release functional self-supporting
      protocells to an aqueous phase, enabling them to interact with physiologically
      relevant matrices.

PMID- 29035357
TI  - Continuous-wave infrared optical gain and amplified spontaneous emission at
      ultralow threshold by colloidal HgTe quantum dots.
AB  - Colloidal quantum dots (QDs) raise more and more interest as solution-processable
      and tunable optical gain materials. However, especially for infrared active QDs,
      optical gain remains inefficient. Since stimulated emission involves multifold
      degenerate band-edge states, population inversion can be attained only at high
      pump power and must compete with efficient multi-exciton recombination. Here, we
      show that mercury telluride (HgTe) QDs exhibit size-tunable stimulated emission
      throughout the near-infrared telecom window at thresholds unmatched by any QD
      studied before. We attribute this unique behaviour to surface-localized states in
      the bandgap that turn HgTe QDs into 4-level systems. The resulting long-lived
      population inversion induces amplified spontaneous emission under continuous-wave
      optical pumping at power levels compatible with solar irradiation and direct
      current electrical pumping. These results introduce an alternative approach for
      low-threshold QD-based gain media based on intentional trap states that paves the
      way for solution-processed infrared QD lasers and amplifiers.

PMID- 29035358
TI  - Topological defects govern crack front motion and facet formation on broken
      surfaces.
AB  - Cracks develop intricate patterns on the surfaces that they create. As faceted
      fracture surfaces are commonly formed by slow tensile cracks in both crystalline
      and amorphous materials, facet formation and structure cannot reflect microscopic
      order. Although fracture mechanics predict that slow crack fronts should be
      straight and form mirror-like surfaces, facet-forming fronts propagate
      simultaneously within different planes separated by steps. Here we show that
      these steps are topological defects of crack fronts and that crack front
      separation into disconnected overlapping segments provides the condition for step
      stability. Real-time imaging of propagating crack fronts combined with surface
      measurements shows that crack dynamics are governed by localized steps that drift
      at a constant angle to the local front propagation direction while their
      increased dissipation couples to long-ranged elasticity to determine front
      shapes. We study how three-dimensional topology couples to two-dimensional
      fracture dynamics to provide a fundamental picture of how patterned surfaces are
      generated.

PMID- 29035359
TI  - Acute myeloid leukaemia disrupts endogenous myelo-erythropoiesis by compromising
      the adipocyte bone marrow niche.
AB  - Acute myeloid leukaemia (AML) is distinguished by the generation of dysfunctional
      leukaemic blasts, and patients characteristically suffer from fatal infections
      and anaemia due to insufficient normal myelo-erythropoiesis. Direct physical
      crowding of bone marrow (BM) by accumulating leukaemic cells does not fully
      account for this haematopoietic failure. Here, analyses from AML patients were
      applied to both in vitro co-culture platforms and in vivo xenograft modelling,
      revealing that human AML disease specifically disrupts the adipocytic niche in
      BM. Leukaemic suppression of BM adipocytes led to imbalanced regulation of
      endogenous haematopoietic stem and progenitor cells, resulting in impaired myelo
      erythroid maturation. In vivo administration of PPARgamma agonists induced BM
      adipogenesis, which rescued healthy haematopoietic maturation while repressing
      leukaemic growth. Our study identifies a previously unappreciated axis between BM
      adipogenesis and normal myelo-erythroid maturation that is therapeutically
      accessible to improve symptoms of BM failure in AML via non-cell autonomous
      targeting of the niche.

PMID- 29035360
TI  - EZH2 promotes degradation of stalled replication forks by recruiting MUS81
      through histone H3 trimethylation.
AB  - The emergence of resistance to poly-ADP-ribose polymerase inhibitors (PARPi)
      poses a threat to the treatment of BRCA1 and BRCA2 (BRCA1/2)-deficient tumours.
      Stabilization of stalled DNA replication forks is a recently identified PARPi
      resistance mechanism that promotes genomic stability in BRCA1/2-deficient
      cancers. Dissecting the molecular pathways controlling genomic stability at
      stalled forks is critical. Here we show that EZH2 localizes at stalled forks
      where it methylates Lys27 on histone 3 (H3K27me3), mediating recruitment of the
      MUS81 nuclease. Low EZH2 levels reduce H3K27 methylation, prevent MUS81
      recruitment at stalled forks and cause fork stabilization. As a consequence, loss
      of function of the EZH2/MUS81 axis promotes PARPi resistance in BRCA2-deficient
      cells. Accordingly, low EZH2 or MUS81 expression levels predict chemoresistance
      and poor outcome in patients with BRCA2-mutated tumours. Moreover, inhibition of
      Ezh2 in a murine Brca2-/- breast tumour model is associated with acquired PARPi
      resistance. Our findings identify EZH2 as a critical regulator of genomic
      stability at stalled forks that couples histone modifications to nuclease
      recruitment. Our data identify EZH2 expression as a biomarker of BRCA2-deficient
      tumour response to chemotherapy.

PMID- 29035361
TI  - Continuous directed evolution of aminoacyl-tRNA synthetases.
AB  - Directed evolution of orthogonal aminoacyl-tRNA synthetases (AARSs) enables site
      specific installation of noncanonical amino acids (ncAAs) into proteins.
      Traditional evolution techniques typically produce AARSs with greatly reduced
      activity and selectivity compared to their wild-type counterparts. We designed
      phage-assisted continuous evolution (PACE) selections to rapidly produce highly
      active and selective orthogonal AARSs through hundreds of generations of
      evolution. PACE of a chimeric Methanosarcina spp. pyrrolysyl-tRNA synthetase
      (PylRS) improved its enzymatic efficiency (kcat/KMtRNA) 45-fold compared to the
      parent enzyme. Transplantation of the evolved mutations into other PylRS-derived
      synthetases improved yields of proteins containing noncanonical residues up to
      9.7-fold. Simultaneous positive and negative selection PACE over 48 h greatly
      improved the selectivity of a promiscuous Methanocaldococcus jannaschii tyrosyl
      tRNA synthetase variant for site-specific incorporation of p-iodo-L
      phenylalanine. These findings offer new AARSs that increase the utility of
      orthogonal translation systems and establish the capability of PACE to
      efficiently evolve orthogonal AARSs with high activity and amino acid
      specificity.

PMID- 29035362
TI  - Changes in microtubule overlap length regulate kinesin-14-driven microtubule
      sliding.
AB  - Microtubule-crosslinking motor proteins, which slide antiparallel microtubules,
      are required for the remodeling of microtubule networks. Hitherto, all
      microtubule-crosslinking motors have been shown to slide microtubules at a
      constant velocity until no overlap remains between them, leading to the breakdown
      of the initial microtubule geometry. Here, we show in vitro that the sliding
      velocity of microtubules, driven by human kinesin-14 HSET, decreases when
      microtubules start to slide apart, resulting in the maintenance of finite-length
      microtubule overlaps. We quantitatively explain this feedback using the local
      interaction kinetics of HSET with overlapping microtubules that cause retention
      of HSET in shortening overlaps. Consequently, the increased HSET density in the
      overlaps leads to a density-dependent decrease in sliding velocity and the
      generation of an entropic force that antagonizes the force exerted by the motors.
      Our results demonstrate that a spatial arrangement of microtubules can regulate
      the collective action of molecular motors through the local alteration of their
      individual interaction kinetics.

PMID- 29035363
TI  - Crystal structures reveal an elusive functional domain of pyrrolysyl-tRNA
      synthetase.
AB  - Pyrrolysyl-tRNA synthetase (PylRS) is a major tool in genetic code expansion
      using noncanonical amino acids, yet its structure and function are not completely
      understood. Here we describe the crystal structure of the previously
      uncharacterized essential N-terminal domain of this unique enzyme in complex with
      tRNAPyl. This structure explains why PylRS remains orthogonal in a broad range of
      organisms, from bacteria to humans. The structure also illustrates why tRNAPyl
      recognition by PylRS is anticodon independent: the anticodon does not contact the
      enzyme. Then, using standard microbiological culture equipment, we established a
      new method for laboratory evolution-a noncontinuous counterpart of the previously
      developed phage-assisted continuous evolution. With this method, we evolved novel
      PylRS variants with enhanced activity and amino acid specificity. Finally, we
      employed an evolved PylRS variant to determine its N-terminal domain structure
      and show how its mutations improve PylRS activity in the genetic encoding of a
      noncanonical amino acid.

PMID- 29035364
TI  - Sympathetic neuron-associated macrophages contribute to obesity by importing and
      metabolizing norepinephrine.
AB  - The cellular mechanism(s) linking macrophages to norepinephrine (NE)-mediated
      regulation of thermogenesis have been a topic of debate. Here we identify
      sympathetic neuron-associated macrophages (SAMs) as a population of cells that
      mediate clearance of NE via expression of solute carrier family 6 member 2
      (SLC6A2), an NE transporter, and monoamine oxidase A (MAOA), a degradation
      enzyme. Optogenetic activation of the sympathetic nervous system (SNS)
      upregulates NE uptake by SAMs and shifts the SAM profile to a more
      proinflammatory state. NE uptake by SAMs is prevented by genetic deletion of
      Slc6a2 or inhibition of the encoded transporter. We also observed an increased
      proportion of SAMs in the SNS of two mouse models of obesity. Genetic ablation of
      Slc6a2 in SAMs increases brown adipose tissue (BAT) content, causes browning of
      white fat, increases thermogenesis, and leads to substantial and sustained weight
      loss in obese mice. We further show that this pathway is conserved, as human
      sympathetic ganglia also contain SAMs expressing the analogous molecular
      machinery for NE clearance, which thus constitutes a potential target for obesity
      treatment.

PMID- 29035365
TI  - Omega-3 fatty acid epoxides are autocrine mediators that control the magnitude of
      IgE-mediated mast cell activation.
AB  - Critical to the function of mast cells in immune responses including allergy is
      their production of lipid mediators, among which only omega-6 (omega-6)
      arachidonate-derived eicosanoids have been well characterized. Here, by employing
      comprehensive lipidomics, we identify omega-3 (omega-3) fatty acid epoxides as
      new mast cell-derived lipid mediators and show that they are produced by PAF-AH2,
      an oxidized-phospholipid-selective phospholipase A2. Genetic or pharmacological
      deletion of PAF-AH2 reduced the steady-state production of omega-3 epoxides,
      leading to attenuated mast cell activation and anaphylaxis following FcERI cross
      linking. Mechanistically, the omega-3 epoxides promote IgE-mediated activation of
      mast cells by downregulating Srcin1, a Src-inhibitory protein that counteracts
      FcERI signaling, through a pathway involving PPARg. Thus, the PAF-AH2-omega-3
      epoxide-Srcin1 axis presents new potential drug targets for allergic diseases.

PMID- 29035366
TI  - Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a
      therapeutic target in glioblastoma.
AB  - Cross-talk among oncogenic signaling and metabolic pathways may create
      opportunities for new therapeutic strategies in cancer. Here we show that
      although acute inhibition of EGFR-driven glucose metabolism induces only minimal
      cell death, it lowers the apoptotic threshold in a subset of patient-derived
      glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated
      glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic
      apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in
      combination with pharmacological stabilization of p53 with the brain-penetrant
      small molecule idasanutlin resulted in synthetic lethality in orthotopic
      glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling
      inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to
      this therapeutic combination. However, detection of rapid inhibitory effects on
      [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission
      tomography, was an effective predictive biomarker of response in vivo. Together,
      these studies identify a crucial link among oncogene signaling, glucose
      metabolism, and cytoplasmic p53, which may potentially be exploited for
      combination therapy in GBM and possibly other malignancies.

PMID- 29035369
TI  - Epigenetic suppression of hippocampal calbindin-D28k by DeltaFosB drives seizure
      related cognitive deficits.
AB  - The calcium-binding protein calbindin-D28k is critical for hippocampal function
      and cognition, but its expression is markedly decreased in various neurological
      disorders associated with epileptiform activity and seizures. In Alzheimer's
      disease (AD) and epilepsy, both of which are accompanied by recurrent seizures,
      the severity of cognitive deficits reflects the degree of calbindin reduction in
      the hippocampal dentate gyrus (DG). However, despite the importance of calbindin
      in both neuronal physiology and pathology, the regulatory mechanisms that control
      its expression in the hippocampus are poorly understood. Here we report an
      epigenetic mechanism through which seizures chronically suppress hippocampal
      calbindin expression and impair cognition. We demonstrate that DeltaFosB, a
      highly stable transcription factor, is induced in the hippocampus in mouse models
      of AD and seizures, in which it binds and triggers histone deacetylation at the
      promoter of the calbindin gene (Calb1) and downregulates Calb1 transcription.
      Notably, increasing DG calbindin levels, either by direct virus-mediated
      expression or inhibition of DeltaFosB signaling, improves spatial memory in a
      mouse model of AD. Moreover, levels of DeltaFosB and calbindin expression are
      inversely related in the DG of individuals with temporal lobe epilepsy (TLE) or
      AD and correlate with performance on the Mini-Mental State Examination (MMSE). We
      propose that chronic suppression of calbindin by DeltaFosB is one mechanism
      through which intermittent seizures drive persistent cognitive deficits in
      conditions accompanied by recurrent seizures.

PMID- 29035367
TI  - Targeting glioma stem cells through combined BMI1 and EZH2 inhibition.
AB  - Glioblastomas are lethal cancers defined by angiogenesis and pseudopalisading
      necrosis. Here, we demonstrate that these histological features are associated
      with distinct transcriptional programs, with vascular regions showing a proneural
      profile, and hypoxic regions showing a mesenchymal pattern. As these regions
      harbor glioma stem cells (GSCs), we investigated the epigenetic regulation of
      these two niches. Proneural, perivascular GSCs activated EZH2, whereas
      mesenchymal GSCs in hypoxic regions expressed BMI1 protein, which promoted
      cellular survival under stress due to downregulation of the E3 ligase RNF144A.
      Using both genetic and pharmacologic inhibition, we found that proneural GSCs are
      preferentially sensitive to EZH2 disruption, whereas mesenchymal GSCs are more
      sensitive to BMI1 inhibition. Given that glioblastomas contain both proneural and
      mesenchymal GSCs, combined EZH2 and BMI1 targeting proved more effective than
      either agent alone both in culture and in vivo, suggesting that strategies that
      simultaneously target multiple epigenetic regulators within glioblastomas may be
      effective in overcoming therapy resistance caused by intratumoral heterogeneity.

PMID- 29035368
TI  - Activation of intestinal hypoxia-inducible factor 2alpha during obesity
      contributes to hepatic steatosis.
AB  - Nonalcoholic fatty liver disease is becoming the most common chronic liver
      disease in Western countries, and limited therapeutic options are available. Here
      we uncovered a role for intestinal hypoxia-inducible factor (HIF) in hepatic
      steatosis. Human-intestine biopsies from individuals with or without obesity
      revealed that intestinal HIF-2alpha signaling was positively correlated with body
      mass index and hepatic toxicity. The causality of this correlation was verified
      in mice with an intestine-specific disruption of Hif2a, in which high-fat-diet
      induced hepatic steatosis and obesity were substantially lower as compared to
      control mice. PT2385, a HIF-2alpha-specific inhibitor, had preventive and
      therapeutic effects on metabolic disorders that were dependent on intestine HIF
      2alpha. Intestine HIF-2alpha inhibition markedly reduced intestine and serum
      ceramide levels. Mechanistically, intestine HIF-2alpha regulates ceramide
      metabolism mainly from the salvage pathway, by positively regulating the
      expression of Neu3, the gene encoding neuraminidase 3. These results suggest that
      intestinal HIF-2alpha could be a viable target for hepatic steatosis therapy.

PMID- 29035370
TI  - Natural killer cells migrate into and control simian immunodeficiency virus
      replication in lymph node follicles in African green monkeys.
AB  - Natural killer (NK) cells play an essential role in antiviral immunity, but
      knowledge of their function in secondary lymphoid organs is incomplete. Lymph
      node follicles constitute a major viral reservoir during infections with HIV-1
      and simian immunodeficiency virus of macaques (SIVmac). In contrast, during
      nonpathogenic infection with SIV from African green monkeys (SIVagm), follicles
      remain generally virus free. We show that NK cells in secondary lymphoid organs
      from chronically SIVagm-infected African green monkeys (AGMs) were frequently
      CXCR5+ and entered and persisted in lymph node follicles throughout the follow-up
      (240 d post-infection). These follicles were strongly positive for IL-15, which
      was primarily presented in its membrane-bound form by follicular dendritic cells.
      NK cell depletion through treatment with anti-IL-15 monoclonal antibody during
      chronic SIVagm infection resulted in high viral replication rates in follicles
      and the T cell zone and increased viral DNA in lymph nodes. Our data suggest
      that, in nonpathogenic SIV infection, NK cells migrate into follicles and play a
      major role in viral reservoir control in lymph nodes.

PMID- 29035372
TI  - MMseqs2 enables sensitive protein sequence searching for the analysis of massive
      data sets.

PMID- 29035371
TI  - lncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via
      Wnt/beta-catenin signaling.
AB  - De novo and acquired resistance, which are largely attributed to genetic
      alterations, are barriers to effective anti-epidermal-growth-factor-receptor
      (EGFR) therapy. To generate cetuximab-resistant cells, we exposed cetuximab
      sensitive colorectal cancer cells to cetuximab in three-dimensional culture.
      Using whole-exome sequencing and transcriptional profiling, we found that the
      long non-coding RNA MIR100HG and two embedded microRNAs, miR-100 and miR-125b,
      were overexpressed in the absence of known genetic events linked to cetuximab
      resistance. MIR100HG, miR-100 and miR-125b overexpression was also observed in
      cetuximab-resistant colorectal cancer and head and neck squamous cell cancer cell
      lines and in tumors from colorectal cancer patients that progressed on cetuximab.
      miR-100 and miR-125b coordinately repressed five Wnt/beta-catenin negative
      regulators, resulting in increased Wnt signaling, and Wnt inhibition in cetuximab
      resistant cells restored cetuximab responsiveness. Our results describe a double
      negative feedback loop between MIR100HG and the transcription factor GATA6,
      whereby GATA6 represses MIR100HG, but this repression is relieved by miR-125b
      targeting of GATA6. These findings identify a clinically actionable, epigenetic
      cause of cetuximab resistance.

PMID- 29035373
TI  - Molecular afterglow imaging with bright, biodegradable polymer nanoparticles.
AB  - Afterglow optical agents, which emit light long after cessation of excitation,
      hold promise for ultrasensitive in vivo imaging because they eliminate tissue
      autofluorescence. However, afterglow imaging has been limited by its reliance on
      inorganic nanoparticles with relatively low brightness and short-near-infrared
      (NIR) emission. Here we present semiconducting polymer nanoparticles (SPNs) <40
      nm in diameter that store photon energy via chemical defects and emit long-NIR
      afterglow luminescence at 780 nm with a half-life of ~6 min. In vivo, the
      afterglow intensity of SPNs is more than 100-fold brighter than that of inorganic
      afterglow agents, and the signal is detectable through the body of a live mouse.
      High-contrast lymph node and tumor imaging in living mice is demonstrated with a
      signal-to-background ratio up to 127-times higher than that obtained by NIR
      fluorescence imaging. Moreover, we developed an afterglow probe, activated only
      in the presence of biothiols, for early detection of drug-induced hepatotoxicity
      in living mice.

PMID- 29035374
TI  - Design of coiled-coil protein-origami cages that self-assemble in vitro and in
      vivo.
AB  - Polypeptides and polynucleotides are natural programmable biopolymers that can
      self-assemble into complex tertiary structures. We describe a system analogous to
      designed DNA nanostructures in which protein coiled-coil (CC) dimers serve as
      building blocks for modular de novo design of polyhedral protein cages that
      efficiently self-assemble in vitro and in vivo. We produced and characterized >20
      single-chain protein cages in three shapes-tetrahedron, four-sided pyramid, and
      triangular prism-with the largest containing >700 amino-acid residues and
      measuring 11 nm in diameter. Their stability and folding kinetics were similar to
      those of natural proteins. Solution small-angle X-ray scattering (SAXS), electron
      microscopy (EM), and biophysical analysis confirmed agreement of the expressed
      structures with the designs. We also demonstrated self-assembly of a tetrahedral
      structure in bacteria, mammalian cells, and mice without evidence of
      inflammation. A semi-automated computational design platform and a toolbox of CC
      building modules are provided to enable the design of protein cages in any
      polyhedral shape.

PMID- 29035375
TI  - Upregulation of the actin cytoskeleton via myocardin leads to increased
      expression of type 1 collagen.
AB  - Liver fibrosis, a model wound healing system, is characterized by excessive
      deposition of extracellular matrix (ECM) in the liver. Although many fibrogenic
      cell types may express ECM, the hepatic stellate cell (HSC) is currently
      considered to be the major effector. HSCs transform into myofibroblast-like
      cells, also known as hepatic myofibroblasts in a process known as activation;
      this process is characterized in particular by de novo expression of smooth
      muscle alpha actin (SM alpha-actin) and type 1 collagen. The family of actins,
      which form the cell's cytoskeleton, are essential in many cellular processes.
      beta-actin and cytoplasmic gamma-actin (gamma-actin) are ubiquitously expressed,
      whereas SM alpha-actin defines smooth muscle cell and myofibroblast phenotypes.
      Thus, SM alpha-actin is tightly associated with multiple functional properties.
      However, the regulatory mechanisms by which actin isoforms might regulate type 1
      collagen remain unclear. In primary HSCs from normal and fibrotic rat liver, we
      demonstrate that myocardin, a canonical SRF cofactor, is upregulated in hepatic
      myofibroblasts and differentially regulates SM alpha-actin, gamma-actin, and beta
      actins through activation of an ATTA box in the SM alpha-actin and a CCAAT box in
      gamma-actin and beta-actin promoters, respectively; moreover, myocardin
      differentially activated serum response factor (SRF) in CArG boxes of actin
      promoters. In addition, myocardin-stimulated Smad2 phosphorylation and RhoA
      expression, leading to increased expression of type 1 collagen in an actin
      cytoskeleton-dependent manner. Myocardin also directly enhanced SRF expression
      and stimulated collagen 1alpha1 and 1alpha2 promoter activities. In addition,
      overexpression of myocardin in vivo during carbon tetrachloride-induced liver
      injury led to increased HSC activation and fibrogenesis. In summary, our data
      suggest that myocardin plays a critical role in actin cytoskeletal dynamics
      during HSC activation, in turn, specifically regulating type I collagen
      expression in hepatic myofibroblasts.

PMID- 29035377
TI  - NME4/nucleoside diphosphate kinase D in cardiolipin signaling and mitophagy.
AB  - Mitophagy is an emerging paradigm for mitochondrial quality control and cell
      homeostasis. Dysregulation of mitophagy can lead to human pathologies such as
      neurodegenerative disorders and contributes to the aging process. Complex protein
      signaling cascades have been described that regulate mitophagy. We have
      identified a novel lipid signaling pathway that involves the phospholipid
      cardiolipin (CL). CL is synthesized and normally confined at the inner
      mitochondrial membrane. However, upon a mitophagic trigger, ie, collapse of the
      inner membrane potential, CL is rapidly externalized to the mitochondrial surface
      with the assistance of the hexameric nucleoside diphosphate kinase D (NME4, NDPK
      D, or NM23-H4). In addition to its NDP kinase activity, NME4/NDPK-D shows
      intermembrane phospholipid transfer activity in vitro and in cellular systems,
      which relies on NME4/NDPK-D interaction with CL, CL-dependent crosslinking of
      inner and outer mitochondrial membranes by symmetrical, hexameric NME4/NDPK-D,
      and a putative NME4/NDPK-D-based CL-transfer pathway. CL exposed at the
      mitochondrial surface then serves as an 'eat me' signal for the mitophagic
      machinery; it is recognized by the LC3 receptor of autophagosomes, targeting the
      dysfunctional mitochondrion to lysosomal degradation. Similar NME4-supported CL
      externalization is likely also involved in apoptosis and inflammatory reactions.

PMID- 29035376
TI  - Oncogenic Epstein-Barr virus recruits Nm23-H1 to regulate chromatin modifiers.
AB  - In cancer progression, metastasis is a major cause of poor survival of patients
      and can be targeted for therapeutic interventions. The first discovered
      metastatic-suppressor Nm23-H1 possesses nucleoside diphosphate kinase, histidine
      kinase, and DNase activity as a broad-spectrum enzyme. Recent advances in cancer
      metastasis have opened new ways for the development of therapeutic molecular
      approaches. In this review, we provide a summary of the current understanding of
      Nm23/NDPKs in the context of viral oncogenesis. We also focused on Nm23-H1
      mediated cellular events with an emphasis on chromatin modifications. How Nm23-H1
      modulates the activities of chromatin modifiers through interaction with Epstein
      Barr virus-encoded oncogenic antigens and related crosstalks are discussed in the
      context of other oncogenic viruses. We also described the current understanding
      of the cellular and viral interactions of Nm23-H1 and their reference to
      transcription regulation and metastasis. Further, we summarized the recent
      therapeutic approaches targeting Nm23 and its potential links to pathways that
      can be exploited by oncogenic viruses.

PMID- 29035378
TI  - Molecular similarities and differences from human pulmonary fibrosis and
      corresponding mouse model: MALDI imaging mass spectrometry in comparative
      medicine.
AB  - Animal models can reproduce some model-specific aspects of human diseases, but
      some animal models translate poorly or fail to translate to the corresponding
      human disease. Here, we develop a strategy to systematically compare human and
      mouse tissues, and conduct a proof-of-concept experiment to identify molecular
      similarities and differences using patients with idiopathic pulmonary fibrosis
      and a bleomycin-induced fibrosis mouse model. Our novel approach employs high
      throughput tissue microarrays (TMAs) of humans and mice, high-resolution matrix
      assisted laser desorption/ionization-Fourier transform-ion cyclotron resonance
      mass spectrometry imaging (MALDI-FT-ICR-MSI) to spatially resolve mass spectra at
      the level of specific metabolites, and hierarchical clustering and pathway
      enrichment analysis to identify functionally similar/different molecular patterns
      and pathways in pathological lesions of humans and mice. We identified a large
      number of common molecules (n=1366) and fewer exclusive molecules in humans
      (n=83) and mice (n=54). Among the common molecules, the 'ascorbate and aldarate
      metabolism' pathway had the highest similarity in human and mouse lesions. This
      proof-of-concept study demonstrates that our novel strategy employing a reliable
      and easy-to-perform experimental design accurately identifies pathways and
      factors that can be directly compared between animal models and human diseases.

PMID- 29035379
TI  - Lobular carcinoma in situ and invasive lobular breast cancer are characterized by
      enhanced expression of transcription factor AP-2beta.
AB  - Transcription factor AP-2beta (TFAP2B) regulates embryonic organ development and
      is overexpressed in alveolar rhabdomyosarcoma, a rare childhood malignancy. Gene
      expression profiling has implicated AP-2beta in breast cancer (BC). This study
      characterizes AP-2beta expression in the mammary gland and in BC. AP-2beta
      protein expression was assessed in the normal mammary gland epithelium, in
      various reactive, metaplastic and pre-invasive neoplastic lesions and in two
      clinical BC cohorts comprising >2000 patients. BCs from various genetically
      engineered mouse (GEM) models were also evaluated. Human BC cell lines served as
      functional models to study siRNA-mediated inhibition of AP-2beta. The normal
      mammary gland epithelium showed scattered AP-2beta-positive cells in the luminal
      cell layer. Various reactive and pre-invasive neoplastic lesions, including
      apocrine metaplasia, usual ductal hyperplasia and lobular carcinoma in situ
      (LCIS) showed enhanced AP-2beta expression. Cases of ductal carcinoma in situ
      (DCIS) were more often AP-2beta-negative (P<0.001). In invasive BC cohorts, AP
      2beta-positivity was associated with the lobular BC subtype (P<0.001), loss of E
      cadherin (P<0.001), a positive estrogen receptor (ER) status (P<0.001), low Ki67
      (P<0.001), low/intermediate Oncotype DX recurrence scores (P<0.001), and
      prolonged event-free survival (P=0.003). BCs from GEM models were all AP-2beta
      negative. In human BC cell lines, AP-2beta expression was independent from ER
      signaling. SiRNA-mediated inhibition of AP-2beta diminished proliferation of
      lobular BC cell lines in vitro. In summary, AP-2beta is a new mammary epithelial
      differentiation marker. Its expression is preferentially retained and enhanced in
      LCIS and invasive lobular BC and has prognostic implications. Our findings
      indicate that AP-2beta controls tumor cell proliferation in this slow-growing BC
      subtype.

PMID- 29035380
TI  - Mixed cell therapy of bone marrow-derived mesenchymal stem cells and articular
      cartilage chondrocytes ameliorates osteoarthritis development.
AB  - Of the many cell-based treatments that have been tested in an effort to
      regenerate osteoarthritic articular cartilage, none have ever produced cartilage
      that compare with native hyaline cartilage. Studies show that different cell
      types lead to inconsistent results and for cartilage regeneration to be
      considered successful, there must be an absence of fibrotic tissue. Here we
      report of a series of experiments in which bone marrow-derived stem cells (BMSCs)
      and articular cartilage chondrocytes (ACCs) were mixed in a 1:1 ratio and tested
      for their ability to enhance cartilage regeneration in three different
      conditions: (1) in an in vitro differentiation model; (2) in an ex vivo cartilage
      defect model implanted subcutaneously in mice; and (3) as an intra-articular
      injection in a meniscectomy-induced OA model in rats. The mixed cells were
      compared with monocultures of BMSCs and ACCs. In all three experimental models
      there was significantly enhanced cartilage regeneration and decreased fibrosis in
      the mixed BMSCs+ACCs group compared with the monocultures. Molecular analysis
      showed a reduction in vascularization and hypertrophy, coupled with higher
      chondrogenic gene expression resulting from the BMSCs+ACCs treatment. Together,
      our data suggest that mixed BMSCs+ACCs treatment is highly chondro-protective and
      is more effective in regenerating damaged cartilage in both the ex vivo cartilage
      defect and post-trauma OA disease models. The results from this approach could
      potentially be used for regeneration of cartilage in OA patients.

PMID- 29035381
TI  - High expression of HOXA13 correlates with poorly differentiated hepatocellular
      carcinomas and modulates sorafenib response in in vitro models.
AB  - Hepatocellular carcinoma (HCC) represents the fifth and ninth cause of mortality
      among male and female cancer patients, respectively and typically arises on a
      background of a cirrhotic liver. HCC develops in a multi-step process, often
      encompassing chronic liver injury, steatosis and cirrhosis eventually leading to
      the malignant transformation of hepatocytes. Aberrant expression of the class I
      homeobox gene family (HOX), a group of genes crucial in embryogenesis, has been
      reported in a variety of malignancies including solid tumors. Among HOX genes,
      HOXA13 is most overexpressed in HCC and is known to be directly regulated by the
      long non-coding RNA HOTTIP. In this study, taking advantage of a tissue
      microarray containing 305 tissue specimens, we found that HOXA13 protein
      expression increased monotonically from normal liver to cirrhotic liver to HCC
      and that HOXA13-positive HCCs were preferentially poorly differentiated and had
      fewer E-cadherin-positive cells. In two independent cohorts, patients with HOXA13
      positive HCC had worse overall survival than those with HOXA13-negative HCC.
      Using HOXA13 immunohistochemistry and HOTTIP RNA in situ hybridization on
      consecutive sections of 16 resected HCCs, we demonstrated that HOXA13 and HOTTIP
      were expressed in the same neoplastic hepatocyte populations. Stable
      overexpression of HOXA13 in liver cancer cell lines resulted in increased colony
      formation on soft agar and migration potential as well as reduced sensitivity to
      sorafenib in vitro. Our results provide compelling evidence of a role for HOXA13
      in HCC development and highlight for the first time its ability to modulate
      response to sorafenib.

PMID- 29035382
TI  - Regulation of heterotrimeric G-protein signaling by NDPK/NME proteins and
      caveolins: an update.
AB  - Heterotrimeric G proteins are pivotal mediators of cellular signal transduction
      in eukaryotic cells and abnormal G-protein signaling plays an important role in
      numerous diseases. During the last two decades it has become evident that the
      activation status of heterotrimeric G proteins is both highly localized and
      strongly regulated by a number of factors, including a receptor-independent
      activation pathway of heterotrimeric G proteins that does not involve the
      classical GDP/GTP exchange and relies on nucleoside diphosphate kinases (NDPKs).
      NDPKs are NTP/NDP transphosphorylases encoded by the nme/nm23 genes that are
      involved in a variety of cellular events such as proliferation, migration, and
      apoptosis. They therefore contribute, for example, to tumor metastasis,
      angiogenesis, retinopathy, and heart failure. Interestingly, NDPKs are
      translocated and/or upregulated in human heart failure. Here we describe recent
      advances in the current understanding of NDPK functions and how they have an
      impact on local regulation of G-protein signaling.

PMID- 29035383
TI  - Extracellular NME proteins: a player or a bystander?
AB  - The Nm23/NME gene family has been under intensive study since Nm23H1/NME1 was
      identified as the first metastasis suppressor. Inverse correlation between the
      expression levels of NME1/2 and prognosis has indeed been demonstrated in
      different tumor cohorts. Interestingly, the presence of NME proteins in the
      extracellular environment in normal and tumoral conditions has also been noted.
      In many reported cases, however, these extracellular NME proteins exhibit anti
      differentiation or oncogenic functions, contradicting their canonical anti
      metastatic action. This emerging field thus warrants further investigation. In
      this review, we summarize the current understanding of extracellular NME
      proteins. A role in promoting stem cell pluripotency and inducing development of
      central nervous system as well as a neuroprotective function of extracellular NME
      have been suggested. Moreover, a tumor-promoting function of extracellular NME
      also emerged at least in some tumor cohorts. In this complex scenario, the
      secretory mechanism through which NME proteins exit cells is far from being
      understood. Recently, some evidence obtained in the Drosophila and cancer cell
      line models points to the involvement of Dynamin in controlling the balance
      between intra- and extracellular levels of NME. Further analyses on extracellular
      NME will lead to a better understanding of its physiological function and in turn
      will allow understanding of how its deregulation contributes to carcinogenesis.

PMID- 29035384
TI  - Effect of anthelmintic treatment on leptin, adiponectin and leptin to adiponectin
      ratio: a randomized-controlled trial.
AB  - Emerging evidence suggests that helminths might confer protection against the
      development of type 2 diabetes. We aimed to assess the role of adipokines in
      mediating the effect of helminths on insulin resistance. Serum samples were
      obtained from a randomized-controlled trial of anthelmintic treatment in an area
      endemic for soil-transmitted helminths (STH), Flores Island, Indonesia. In STH
      infected subjects, anthelmintic treatment significantly increased the ratio of
      leptin to adiponectin (treatment effect factor (95% confidence interval (CI)), P
      value for interaction: 1.20 (1.06-1.35), P=0.010), which largely stemmed from a
      significant reduction in adiponectin (0.91 (0.85-0.98), P=0.020) and a trend for
      an increase in leptin level (1.10 (1.00-1.21), P=0.119). No significant effect on
      resistin level was observed. This increase in leptin to adiponectin ratio seemed
      to contribute to the observed effect of deworming on increased insulin resistance
      (IR) as adjustment for leptin to adiponectin ratio attenuated the effect on IR
      from 1.07 (1.01-1.14, P=0.023) to 1.05 (0.99-1.11, P=0.075). Anthelmintic
      treatment in STH-infected subjects increases leptin to adiponectin ratio which
      may in small part contribute to the modest increase in IR. Further studies will
      be needed to assess the effect of the changes in adipokine levels on the host
      immune response and metabolism.

PMID- 29035386
TI  - The importance of being earnest in post-publication review: scientific fraud and
      the scourges of anonymity and excuses.

PMID- 29035385
TI  - Class 2 CRISPR-Cas RNA-guided endonucleases: Swiss Army knives of genome editing.
AB  - CRISPR-Cas is a bacterial defense system against phage infection and nucleic acid
      invasion. Class 2 type II CRISPR-Cas9 has also been widely used for genome
      engineering. Here, we review novel insights into the CRISPR class 2 type V
      enzymes, specifically Cpf1 and C2c1, which display different DNA-recognition and
      cleavage characteristics than those of Cas9, the best-characterized member of
      class 2. Recent structures of these ribonucleoprotein complexes that capture
      several stages of the endonuclease reaction have provided molecular details of
      recognition, unzipping and cleavage of the target DNA, allowing their comparison
      with Cas9. A detailed understanding of these mechanisms is crucial for improving
      these genome engineering tools and expanding the genomic space that can be
      targeted.

PMID- 29035387
TI  - Stromal PTEN inhibits the expansion of mammary epithelial stem cells through
      Jagged-1.
AB  - This corrects the article DOI: 10.1038/onc.2016.383.

PMID- 29035388
TI  - A novel HER2 gene body enhancer contributes to HER2 expression.
AB  - The transcriptional regulation of the human epidermal growth factor receptor-2
      (HER2) contributes to an enhanced HER2 expression in HER2-positive breast cancers
      with HER2 gene amplification and HER2-low or HER2-negative breast cancers
      following radiotherapy or endocrine therapy, and this drives tumorigenesis and
      the resistance to therapy. Epigenetic mechanisms are critical for transcription
      regulation, however, such mechanisms in the transcription regulation of HER2 are
      limited to the involvement of tri-methylated histone 3 lysine 4 (H3K4me3) and
      acetylated histone 3 lysine 9 (H3K9ac) at the HER2 promoter region. Here, we
      report the identification of a novel enhancer in the HER2 3' gene body, which we
      have termed HER2 gene body enhancer (HGE). The HGE starts from the 3' end of
      intron 19 and extends into intron 22, possesses enhancer histone modification
      marks in specific cells and enhances the transcriptional activity of the HER2
      promoters. We also found that TFAP2C, a known regulator of HER2, binds to HGE and
      is required for its enhancer function and that DNA methylation in the HGE region
      inhibits the histone modifications characterizing enhancer and is inversely
      correlated with HER2 expression in breast cancer samples. The identification of
      this novel enhancer sheds a light on the roles of epigenetic mechanisms in HER2
      transcription, in both HER2-positive breast cancer samples and individuals with
      HER2-low or HER2-negative breast cancers undergoing radiotherapy or endocrine
      therapy.

PMID- 29035389
TI  - 'MCC' protein interacts with E-cadherin and beta-catenin strengthening cell-cell
      adhesion of HCT116 colon cancer cells.
AB  - E-cadherin and beta-catenin are key proteins that are essential in the formation
      of the epithelial cell layer in the colon but their regulatory pathways that are
      disrupted in cancer metastasis are not completely understood. Mutated in
      colorectal cancer (MCC) is a tumour suppressor gene that is silenced by promoter
      methylation in colorectal cancer and particularly in patients with increased
      lymph node metastasis. Here, we show that MCC methylation is found in 45% of
      colon and 24% of rectal cancers and is associated with proximal colon, poorly
      differentiated, circumferential and mucinous tumours as well as increasing T
      stage and larger tumour size. Knockdown of MCC in HCT116 colon cancer cells
      caused a reduction in E-cadherin protein level, which is a hallmark of epithelial
      mesenchymal transition in cancer, and consequently diminished the E-cadherin/beta
      catenin complex. MCC knockdown disrupted cell-cell adhesive strength and
      integrity in the dispase and transepithelial electrical resistance assays,
      enhanced hepatocyte growth factor-induced cell scatter and increased tumour cell
      invasiveness in an organotypic assay. The Src/Abl inhibitor dasatinib, a
      candidate anti-invasive drug, abrogated the invasive properties induced by MCC
      deficiency. Mechanistically, we establish that MCC interacts with the E
      cadherin/beta-catenin complex. These data provide a significant advance in the
      current understanding of cell-cell adhesion in colon cancer cells.

PMID- 29035390
TI  - Epigenetic silencing of the dual-role signal mediator, ANGPTL4 in tumor tissues
      and its overexpression in the urothelial carcinoma microenvironment.
AB  - Urothelial carcinoma (UC) carcinogenesis has been hypothesized to occur through
      epigenetic repression of tumor-suppressor genes (TSGs). By quantitative real-time
      polymerase chain reaction array, we found that one potential TSG, angiopoietin
      like 4 (ANGPTL4), was expressed at very low levels in all bladder cancer cell
      lines we examined. Previous studies had demonstrated that ANGPTL4 is highly
      expressed in some cancers, but downregulated, by DNA methylation, in others.
      Consequently, owing to these seemingly conflicting functions in distinct cancers,
      the precise role of ANGPTL4 in the etiology of UC remains unclear. In this study,
      using methylation-specific PCR and bisulfite pyrosequencing, we show that ANGPTL4
      is transcriptionally repressed by DNA methylation in UC cell lines and primary
      tumor samples, as compared with adjacent noncancerous bladder epithelium.
      Functional studies further demonstrated that ectopic expression of ANGPTL4
      potently suppressed UC cell proliferation, monolayer colony formation in vitro,
      and invasion, migration, and xenograft formation in vivo. Surprisingly,
      circulating ANGPTL4 was significantly higher in plasma samples from UC patients
      than normal control, suggesting it might be secreted from other cell types.
      Interestingly, our data also indicated that exogenous cANGPTL4 could promote cell
      proliferation and cell migration via activation of signaling through the
      Erk/focal adhesion kinase axis. We further confirmed that mouse xenograft tumor
      growth could be promoted by administration of exogenous cANGPTL4. Finally,
      immunohistochemistry demonstrated that ANGPTL4 was downregulated in tumor cells
      but overexpressed in tumor adjacent stromal tissues of muscle-invasive UC tissue
      samples. In conclusion, our data support dual roles for ANGPTL4 in UC
      progression, either as a tumor suppressor or oncogene, in response to
      microenvironmental context.

PMID- 29035392
TI  - Long-term outcome of mixed chimerism after stem cell transplantation for
      thalassemia major conditioned with busulfan and cyclophosphamide.
AB  - Mixed chimerism (MC) occurs frequently after allogeneic hematopoietic stem cell
      transplantation (HSCT) for thalassemia major (TM) and may be associated with
      rejection. We report the outcome of MC in 132 TM patients conditioned with
      Busulphan/Cyclophosphamide, who had successful engraftment and had ?1 year follow
      up. Chimerism was first assessed at day +28, then every 3-9 months or more
      frequently if there was MC. If rejection was suspected, immunosuppression was
      stopped and donor-lymphocyte infusion (DLI) was given if there was no response.
      Among 132 patients, aged 7 years (range: 2-24), 46/132 (34.8%) had MC in the
      first year, 32/46 (69.6%) at day +28 and another 14 (30%) between day +28 and 1
      year post HSCT. MC was quantified at level 1 (residual host chimerism (RHC) <10%)
      in 20 (43.5%), level II (RHC 10-25%) in 14 (30.4%) and level III (RHC >25%) in 12
      (26.1%). On tapering immunosuppression, 15 (32.6%) developed acute GvHD and 8
      (17.4%) had chronic GvHD with reversal to complete chimerism (CC). DLI was
      administered to 5/46 (10.9%), 1 evolved to CC but 4 rejected the graft. At median
      follow-up of 60 months (range: 16-172), 20/46 (43.5%) had CC, 18/46 (39.1%) had
      persistent MC with hemoglobin of 11.5 g/dL (range: 8.4-13.6), whereas 8 (17.4%)
      rejected the graft. Close monitoring and early intervention is needed with
      increasing recipient chimerism. Novel strategies are required for preventing
      graft rejection.

PMID- 29035391
TI  - A gammaherpesvirus provides protection against allergic asthma by inducing the
      replacement of resident alveolar macrophages with regulatory monocytes.
AB  - The hygiene hypothesis postulates that the recent increase in allergic diseases
      such as asthma and hay fever observed in Western countries is linked to reduced
      exposure to childhood infections. Here we investigated how infection with a
      gammaherpesvirus affected the subsequent development of allergic asthma. We found
      that murid herpesvirus 4 (MuHV-4) inhibited the development of house dust mite
      (HDM)-induced experimental asthma by modulating lung innate immune cells.
      Specifically, infection with MuHV-4 caused the replacement of resident alveolar
      macrophages (AMs) by monocytes with regulatory functions. Monocyte-derived AMs
      blocked the ability of dendritic cells to trigger a HDM-specific response by the
      TH2 subset of helper T cells. Our results indicate that replacement of embryonic
      AMs by regulatory monocytes is a major mechanism underlying the long-term
      training of lung immunity after infection.

PMID- 29035393
TI  - Donor-lymphocyte infusion following haploidentical hematopoietic cell
      transplantation with peripheral blood stem cell grafts and PTCy.
AB  - Donor-lymphocyte infusion (DLI) for relapse following haploidentical
      hematopoietic cell transplantation (haploHCT) with post-transplant
      cyclophosphamide (PTCy) has been described in recipients of bone marrow grafts,
      but not recipients of G-CSF mobilized peripheral blood (PB) grafts. We
      retrospectively identified patients who underwent DLI following PB-haploHCT with
      PTCy for relapse, or loss of chimerism (LOC). Twelve patients (57%) received DLI
      for hematologic relapse/persistent disease, seven (33%) for extramedullary
      relapse and two (10%) for LOC. Sixteen (76%) received chemotherapy prior to DLI,
      which did not correlate with response. The most common first dose was 1 * 106
      CD3+ cells/kg. Two patients developed grade I aGvHD post DLI, one had grade II
      and two had grade III. One developed mild skin cGvHD 1361 days post DLI. Pre-DLI
      aGvHD predicted post-DLI aGvHD (P=0.025). Six patients achieved CR after DLI for
      overt relapse, one achieved full donor chimerism after LOC. Patients with LOC or
      EM relapse had superior relapse-free survival following DLI (P=0.029). DLI
      following PB-haploHCT with PTCy is a viable salvage therapy for overt relapse or
      LOC without a substantial increase in GvHD, and donor lymphocytes may be
      collected simultaneously with graft collection to facilitate availability in
      patients at high risk of relapse.

PMID- 29035396
TI  - Successful correction of familial hemophagocytic lymphohistiocytosis using
      prenatal genetic testing and preemptive hematopoietic stem cell transplantation.

PMID- 29035395
TI  - Replacing carmustine by thiotepa and cyclophosphamide for autologous stem cell
      transplantation in Hodgkin's and non-Hodgkin's B-cell lymphoma.
AB  - This study aimed to compare the real-life results of TECAM, a thiotepa-based
      conditioning regimen consisting of thiotepa (40 mg/m2 days -5 to -2), etoposide
      (200 mg/m2 days -6 to -3), cytarabine (200 mg/m2 days -4 to -1), cyclophosphamide
      (60 mg/kg day -3), and melphalan (60 mg/m2 days -2 to -1) with that of the
      conventional carmustine-based regimen BEAM. We reviewed 125 consecutive patients
      who underwent a first autologous transplantation (ASCT) for B-cell lymphomas at a
      large tertiary transplantation center between 1999 and 2014. TECAM (n=65) and
      BEAM (n=60) had comparable results (3yPFS 49 vs 62%, P=0.16; 3yOS 64 vs 71%,
      P=0.44; TRM 1.6 vs 5%, P=0.35) without a difference in toxicity or time to
      engraftment. Notably, comparable outcomes were observed even though patients
      treated with TECAM were older (55 vs 44) and had a trend towards more prior lines
      of therapy (>2 prior lines: 43 vs 27%, P=0.08). In this regard, 23% of TECAM
      patients were over the age of 65 yet could withstand therapy with similar results
      to younger patients. We conclude that, replacing carmustine by thiotepa and
      cyclophosphamide for ASCT conditioning, has comparable efficacy and safety
      profiles with a possible advantage in older patients.

PMID- 29035397
TI  - Engender trust and edify.

PMID- 29035394
TI  - Infusion of autograft natural killer cell/CD14+HLA-DRDIM cell ratio predicts
      survival in lymphoma post autologous stem cell transplantation.
AB  - The infusion of autograft absolute lymphocyte count (A-ALC) and autograft natural
      killer cells (A-NKC) are prognostic factors for overall survival (OS) and PFS in
      non-Hodgkin's lymphoma (NHL) patients undergoing autologous peripheral blood
      hematopoietic stem cell transplantation (APBHSCT). The human monocytic CD14+HLA
      DRDIM cells are associated with worse prognosis in NHL. Thus, we investigated
      whether the autograft A-NKC/A-CD14+HLA-DRDIM ratio predicts survival in NHL. In a
      total of 111 NHL patients, we analyzed apheresis collection samples for the
      content of A-NKC and A-CD14+HLA-DRDIM. With a median follow-up of 57.2 months
      (range: 2.1-84.6 months), patients with an A-NKC/A-CD14+HLA-DRDIM ratio of ?0.29
      experienced superior OS (5-year OS rates of 84% (95% confidence interval (CI), 72
      91%) vs 48% (95% CI, 34-62%), P<0.0002, respectively) and PFS (5-year PFS rates
      of 59% (95% CI, 47-71%) vs 32% (95% CI, 20-48%), P<0.002, respectively).
      Multivariate analysis revealed that A-NKC/A-CD14+HLA-DRDIM ratio was an
      independent predictor for PFS (hazard ratio (HR)=0.56, 95% CI, 0.32-0.96, P<0.03)
      and OS (HR=0.34, 95% CI, 0.16-0.68, P<0.002). The A-NKC/A-CD14+HLA-DRDIM ratio
      provides a platform to target specific autograft immune effector cells to improve
      clinical outcomes in NHL patients undergoing APBHSCT.

PMID- 29035398
TI  - Risks factors and timing of genital human papillomavirus (HPV) infection in
      female stem cell transplant survivors: a longitudinal study.
AB  - This longitudinal single-center study describes the timing and risk factors for
      genital human papillomavirus (HPV) disease in women after allogeneic
      hematopoietic cell transplantation (HCT). Between 1994 and 2014, 109 females
      underwent HCT of whom 82 surviving transplant for >1 year had regular,
      comprehensive genital tract assessment and treatment of HPV disease. The
      cumulative proportions of any genital HPV infection at 1, 3, 5, 10 and 20 years
      were 4.8%, 14.9%, 28.1%, 36.7% and 40.9%, respectively. Demographic, disease
      related factors, chronic GvHD (cGvHD) and its treatment were analyzed for their
      association with persistent, multifocal or severe genital HPV disease. Pre
      transplant HPV disease was strongly associated with any posttransplant HPV (odds
      ratio (OR)=6.5, 95% confidence interval (CI)=1.65-25.85, P=0.008). Having either
      extensive or genital cGvHD was associated with increased risk of any HPV disease
      (OR=5.7, 95% CI=1.90-17.16, P=0.002) and a higher risk for severe genital
      dysplasia (CIN II-III/VIN II-III; OR=13.1, 95% CI=1.59-108.26, P=0.017), but no
      one developed HPV-related genital cancer. Persistent, multifocal or severe HPV
      disease occurred more frequently than in healthy populations. Women with
      extensive cGvHD, genital cGvHD or pre-transplant HPV are at greatest risk for
      post-transplant HPV disease. Early initiation of annual screening, comprehensive
      genital tract assessment and active management are cornerstones of their
      gynecology care.

PMID- 29035399
TI  - Towards zero-threshold optical gain using charged semiconductor quantum dots.
AB  - Colloidal semiconductor quantum dots are attractive materials for the realization
      of solution-processable lasers. However, their applications as optical-gain media
      are complicated by a non-unity degeneracy of band-edge states, because of which
      multiexcitons are required to achieve the lasing regime. This increases the
      lasing thresholds and leads to very short optical gain lifetimes limited by
      nonradiative Auger recombination. Here, we show that these problems can be at
      least partially resolved by employing not neutral but negatively charged quantum
      dots. By applying photodoping to specially engineered quantum dots with impeded
      Auger decay, we demonstrate a considerable reduction of the optical gain
      threshold due to suppression of ground-state absorption by pre-existing carriers.
      Moreover, by injecting approximately one electron per dot on average, we achieve
      a more than twofold reduction in the amplified spontaneous emission threshold,
      bringing it to the sub-single-exciton level. These measurements indicate the
      feasibility of 'zero-threshold' gain achievable by completely blocking the band
      edge state with two electrons.

PMID- 29035400
TI  - Protein recognition by a pattern-generating fluorescent molecular probe.
AB  - Fluorescent molecular probes have become valuable tools in protein research;
      however, the current methods for using these probes are less suitable for
      analysing specific populations of proteins in their native environment. In this
      study, we address this gap by developing a unimolecular fluorescent probe that
      combines the properties of small-molecule-based probes and cross-reactive sensor
      arrays (the so-called chemical 'noses/tongues'). On the one hand, the probe can
      detect different proteins by generating unique identification (ID) patterns, akin
      to cross-reactive arrays. On the other hand, its unimolecular scaffold and
      selective binding enable this ID-generating probe to identify combinations of
      specific protein families within complex mixtures and to discriminate among
      isoforms in living cells, where macroscopic arrays cannot access. The ability to
      recycle the molecular device and use it to track several binding interactions
      simultaneously further demonstrates how this approach could expand the
      fluorescent toolbox currently used to detect and image proteins.

PMID- 29035401
TI  - Skydiving and the risk of cervical disc herniation.
AB  - The skydiving/parachuting sport which has recently gained popularity is also
      known for its accidents and injuries. However, there are a few studies related to
      its occupational ergonomic risks and occupational musculoskeletal diseases. It
      has been reported that the sudden hyperextension of the neck during the parachute
      opening, so called opening shock results in neck pain. It has been found that the
      jumpers are subjected to an average deceleration of 3-5 times the earth's
      gravitational acceleration (3-5 G) during parachute opening shock. It is
      considered that the spinal cord is destabilized by the impact of this force. This
      study presents the occupational cervical disc herniation occurring in the case of
      a subject who has been working as a skydiving/parachuting instructor for 25
      years, and the ergonomic risks specific to the sports of skydiving. There is a
      requirement for systematic and representative studies related to the
      administrative measures to be taken in order to prevent the occupational diseases
      that may occur in the case of skydivers, the personal protective equipment to be
      used, and the employee. Int J Occup Med Environ Health 2018;31(2):243-249.

PMID- 29035402
TI  - Respiratory parameters at varied altitudes in intermittent mining work.
AB  - OBJECTIVES: Workers in the mining industry in altitude are subjected to several
      risk factors, e.g., airborne silica and low barometric pressure. The aim of this
      study has been to assess the risks for this work category, evaluating single risk
      factors as airborne silica, altitude and work shift, and relating them with
      cardiovascular and ventilatory parameters. MATERIAL AND METHODS: Healthy miners
      employed in a mining company, Chile, working at varied altitudes, and subjected
      to unusual work shifts, were evaluated. Cardiovascular and respiratory parameters
      were investigated. Exposure to airborne silica was evaluated and compared to
      currently binding exposure limits. RESULTS: At varied altitudes and work shifts,
      alterations emerged in haemoglobin, ventilation and respiratory parameters,
      related to employment duration, due to compensatory mechanisms for hypoxia.
      Haemoglobin increased with altitude, saturation fell down under 90% in the
      highest mines. The multiple linear regression analysis showed a direct
      relationship, in the higher mine, between years of exposure to altitude and
      increased forced vital capacity percent (FVC%), and forced expiratory volume in 1
      s (FEV1). An inverse relationship emerged between forced vital capacity (FVC) and
      years of exposure to airborne silica. In the workplace Mina Subterranea (MT
      3600), statistically significant inverse relationship emerged between the
      Tiffeneau index and body weight. CONCLUSIONS: The working conditions in the
      mining industry in altitude appeared to be potentially pathogenic; further
      investigations should be realized integrating risk assessment protocols even in
      consideration of their undeniable unconventionality. Int J Occup Med Environ
      Health 2018;31(2):129-138.

PMID- 29035403
TI  - [Polymorphism of genes encoding proteins of DNA repair vs. occupational and
      environmental exposure to lead, arsenic and pesticides].
AB  - Genetic polymorphism is associated with the occurrence of at least 2 different
      alleles in the locus with a frequency higher than 1% in the population. Among
      polymorphisms we can find single nucleotide polymorphism (SNP) and polymorphism
      of variable number of tandem repeats. The presence of certain polymorphisms in
      genes encoding DNA repair enzymes is associated with the speed and efficiency of
      DNA repair and can protect or expose humans to the effects provoked by
      xenobiotics. Chemicals, such as lead, arsenic pesticides are considered to
      exhibit strong toxicity. There are many different polymorphisms in genes encoding
      DNA repair enzymes, which determine the speed and efficiency of DNA damage repair
      induced by these xenobiotics. In the case of lead, the influence of various
      polymorphisms, such as APE1 (apurinic/apyrimidinic endonuclease 1) (rs1130409),
      hOGG1 (human 8-oxoguanine glycosylase) (rs1052133), XRCC1 (X-ray repair cross
      complementing protein group 1) (rs25487), XRCC1 (rs1799782) and XRCC3 (X-ray
      repair cross-complementing protein group 3) (rs861539) were described. For
      arsenic polymorphisms, such as ERCC2 (excision repair cross-complementing)
      (rs13181), XRCC3 (rs861539), APE1 (rs1130409) and hOGG1 (rs1052133) were
      examined. As to pesticides, separate and combined effects of polymorphisms in
      genes encoding DNA repair enzymes, such as XRCC1 (rs1799782), hOGG1 (rs1052133),
      XRCC4 (X-ray repair cross-complementing protein group 4) (rs28360135) and the
      gene encoding the detoxification enzyme PON1 paraoxonase (rs662) were reported.
      Med Pr 2018;69(2):225-235.

PMID- 29035404
TI  - [Biological significance of chromium III for the human organism].
AB  - Currently, chromium is probably the most controversial transition metal. In
      recent publications it is clearly stated that it is not an essential
      micronutrient and should be considered to have a pharmacological effect.
      Conflicting scientific reports along with a huge amount of dietary supplements,
      as well as dietary and sports nutrients available on the market have prompted the
      authors to investigate the available information on the range of possible
      application, efficacy and safety of products containing salts or chelates of
      chromium III. The authors reviewed articles in electronic databases for the years
      1959-2016, and selected works describing the biochemical, physiological and toxic
      properties of chromium salts and chelates and the range of possible applications
      in medicine, dietetics and sport. A critical analysis of reports dealing with the
      effect of chromium on the carbohydrate and lipid metabolism, body composition,
      lean body mass and sports performance was carried out. The authors indicated
      papers analyzing the mechanism of action of chromium in the cognitive and
      affective disorders. Much attention has been paid to the safety use of chromium
      III supplements. There are still some unsolved issues. In the field of
      toxicology, a limited number of reports about environmental exposure to trivalent
      chromium in the workplace draws our attention. In the field of biochemical
      research, there is still a need to clarify the mechanism of psychiatric and
      endocrinological activity, especially in conjunction with the immune system. Med
      Pr 2018;69(2):211-223.

PMID- 29035405
TI  - Visible-light-mediated cleavage of polymer chains under physiological conditions
      via quinone photoreduction and trimethyl lock.
AB  - We introduce a click and visible-light triggered unclick approach via thio-bromo
      reaction and hydroquinone photoreduction/trimethyl lock cleavage for polymer
      modifications. Both reactions can be carried out in water and at ambient
      temperature, enabling preparation of bioorthogonal hydrogels for encapsulation
      and controlled release of various cells.

PMID- 29035406
TI  - Novel activity-based probes for N-acylethanolamine acid amidase.
AB  - The cysteine hydrolase, N-acylethanolamine acid amidase (NAAA) is a promising
      target for analgesic and anti-inflammatory drugs. Here, we describe the
      development of two unprecedented NAAA-reactive activity-based probes as research
      tools for application in the discovery of new inhibitors and for the in-depth
      characterization of NAAA in its cellular environment.

PMID- 29035407
TI  - Oxygen-insensitive phosphorescence in water from a Pt-doped supramolecular array.
AB  - A supramolecular array consisting of polyvinylpyridine decorated with adamantyl
      substituted Pt(ii) complexes is described. Upon complexation of the adamantyl
      units with cyclodextrins, a transfer into the aqueous phase can be achieved
      leading to an oxygen-insensitive phosphorescence. The unique properties arise
      from a diffusional shielding of the emitters from the environment provided by the
      compact self-assembled array.

PMID- 29035415
TI  - N- to C-sulfonyl photoisomerisation of dihydropyridinones: a synthetic and
      mechanistic study.
AB  - The scope and limitations of a photoinitiated N- to C-sulfonyl migration process
      within a range of dihydropyridinones is assessed. This sulfonyl transfer proceeds
      without erosion of either diastereo- or enantiocontrol, and is general across a
      range of N-sulfonyl substituents (SO2R; R = Ph, 4-MeC6H4, 4-MeOC6H4, 4-NO2C6H4,
      Me, Et) as well as C(3)-(aryl, heteroaryl, alkyl and alkenyl) and C(4)-(aryl and
      ester) substitution. Crossover reactions indicate an intermolecular step is
      operative within the formal migration process, although no crossover from C
      sulfonyl products was observed. EPR studies indicate the intermediacy of a
      sulfonyl radical and a mechanism is proposed based upon these observations.

PMID- 29035417
TI  - Relative performance of three stream bed stability indices as indicators of
      stream health.
AB  - Bed stability is an important stream habitat attribute because it affects
      geomorphology and biotic communities. Natural resource managers desire indices of
      bed stability that can be used under a wide range of geomorphic conditions, are
      biologically meaningful, and are easily incorporated into sampling protocols. To
      eliminate potential bias due to presence of instream wood and increase precision
      of stability values, we modified a stream bed instability index (ISI) to include
      measurements of bankfull depth (d bf) and median particle diameter (D 50) only in
      riffles and increased the pebble count to decrease variability (i.e., increase
      precision) in D 50 . The new riffle-based instability index (RISI) was compared
      to two established indices: ISI and the riffle stability index (RSI). RISI and
      ISI were strongly associated with each other but neither was closely associated
      with RSI. RISI and ISI were closely associated with both a diatom- and two
      macrovertebrate-based stream health indices, but RSI was only weakly associated
      with the macroinvertebrate indices. Unexpectedly, precision of D 50 did not
      differ between RISI and ISI. Results suggest that RISI is a viable alternative to
      both ISI and RSI for evaluating bed stability in multiple stream types. With few
      data requirements and a simple protocol, RISI may also better conform to riffle
      based sampling methods used by some water quality practitioners.

PMID- 29035418
TI  - Multi-criteria evaluation of hydro-geological and anthropogenic parameters for
      the groundwater vulnerability assessment.
AB  - Groundwater contamination assessment is a challenging task due to inherent
      complex dynamisms associated with the groundwater. DRASTIC is a very widely used
      rapid regional tool for the assessment of vulnerability of groundwater to
      contamination. DRASTIC has many lacunas in the form of subjectivities associated
      with weights and ratings of its hydro-geological parameters, and, therefore, the
      accuracy of the DRASTIC-based vulnerability map is questioned. The present study
      demonstrates the optimisation of the DRASTIC parameters along with a scientific
      consideration to the anthropogenic factors causing groundwater contamination. The
      resulting scientific consistent weights and ratings to DRASTIC parameters assist
      in the development of a very precise groundwater vulnerability map highlighting
      different zones of different gravity of contamination. One of the most important
      aspects of this study is that we have considered the impact of vadose zone in a
      very comprehensive manner by considering every sub-surface layer from the earth
      surface to the occurrence of groundwater. The study area for our experiment is
      Fatehgarh Sahib district of Punjab which is facing several groundwater issues.

PMID- 29035419
TI  - Band-gap engineering of halogenated silicon nanowires through molecular doping.
AB  - In this work, we address the effects of molecular doping on the electronic
      properties of fluorinated and chlorinated silicon nanowires (SiNWs), in
      comparison with those corresponding to hydrogen-passivated SiNWs. Adsorption of n
      type dopant molecules on hydrogenated and halogenated SiNWs and their
      chemisorption energies, formation energies, and electronic band gap are studied
      by using density functional theory calculations. The results show that there are
      considerable charge transfers and strong covalent interactions between the dopant
      molecules and the SiNWs. Moreover, the results show that the energy band gap of
      SiNWs changes due to chemical surface doping and it can be further tuned by
      surface passivation. We conclude that a molecular based ex-situ doping, where
      molecules are adsorbed on the surface of the SiNW, can be an alternative path to
      conventional doping. Graphical abstract Molecular doping of halogenated silicon
      nanowires.

PMID- 29035420
TI  - Modeling the secondary structures of the peptaibols antiamoebin I and zervamicin
      II modified with D-amino acids and proline analogues.
AB  - Antiamoebin I (AAM-I) and zervamicin II (Zrv-IIB) are peptaibols that exert
      antibiotic activity through the insertion/disruption of cell membranes. In this
      study, we investigated how the folding of these peptaibols are affected when some
      of their native residues are replaced with proline analogues and asymmetrical D
      alpha,alpha-dialkyl glycines (two classes of noncanonical amino acids).
      Systematic substitutions of native Aib, Pro, Hyp, and Iva residues were performed
      to elucidate the folding properties of the modified peptaibols incorporating
      noncanonical residues. The secondary structure of a peptaibol influences its
      ability to incorporate into membranes and therefore its function. Our findings
      reveal that native Zrv-IIB unfolds considerably in water. The presence of Iva and
      the noncanonical proline analogue cis-3-amino-L-proline (ALP) in both peptaibols
      induces helical structures. Inserting asymmetric glycines such as alpha-methyl-D
      leucine (MDL) and alpha-methyl-D-phenylalanine (MDP) into the peptaibols induces
      folding. This preorganization in water may help to overcome the energy barrier
      required for peptaibol insertion into the membrane, as well as to facilitate the
      formation of transmembrane channels. Graphical abstract AAM-I and Zrv-IIB
      peptidomimetics carrying MDL and ALP noncanonical amino acids, exhibiting
      improved helical secondary structure in water.

PMID- 29035421
TI  - Updated Guideline May Improve the Recognition and Diagnosis of Hypertension in
      Children and Adolescents; Review of the 2017 AAP Blood Pressure Clinical Practice
      Guideline.
AB  - PURPOSE OF REVIEW: Hypertension in children and adolescents is under-recognized
      and under-diagnosed in clinical practice. The 2017 AAP Clinical Practice
      Guideline for Screening and Management of High Blood Pressure in Children and
      Adolescents provides updated recommendations that may improve hypertension
      identification and management. RECENT FINDINGS: The AAP blood pressure guideline
      recommends annual screening for hypertension in children at preventive care
      visits and targeted routine screening in high-risk populations. A simplified
      blood pressure screening table is provided for easier recognition of blood
      pressures that may require attention. Normative blood pressure tables have been
      revised to include only data from normal-weight children as more representative
      of a healthy population. Classification of blood pressure in adolescents has been
      simplified to threshold values consistent with adult guidelines. The updated AAP
      blood pressure guideline has clarified and simplified recommendations for
      hypertension screening, diagnosis, and management based on a systematic review of
      current best evidence.

PMID- 29035422
TI  - The Use of Telemedicine and Mobile Technology to Promote Population Health and
      Population Management for Psychiatric Disorders.
AB  - PURPOSE OF REVIEW: This article discusses recent applications in telemedicine to
      promote the goals of population health and population management for people
      suffering psychiatric disorders. RECENT FINDINGS: The use of telemedicine to
      promote collaborative care, self-monitoring and chronic disease management, and
      population screening has demonstrated broad applicability and effectiveness.
      Collaborative care using videoconferencing to facilitate mental health specialty
      consults has demonstrated effectiveness in the treatment of depression, PTSD, and
      also ADHD in pediatric populations. Mobile health is currently being harnessed to
      monitor patient symptom trajectories with the goal of using machine learning
      algorithms to predict illness relapse. Patient portals serve as a bridge between
      patients and providers. They provide an electronically secure shared space for
      providers and patients to collaborate and optimize care. To date, research has
      supported the effectiveness of telemedicine in promoting population health.
      Future endeavors should focus on developing the most effective clinical protocols
      for using these technologies to ensure long-term use and maximum effectiveness in
      reducing population burden of mental health.

PMID- 29035424
TI  - CYP21A2 mutation update: Comprehensive analysis of databases and published
      genetic variants.
AB  - Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders
      of adrenal steroidogenesis. Disorders in steroid 21-hydroxylation account for
      over 95% of patients with CAH. Clinically, the 21-hydroxylase deficiency has been
      classified in a broad spectrum of clinical forms, ranging from severe or
      classical, to mild late onset or non-classical. Known allelic variants in the
      disease causing CYP21A2 gene are spread among different sources. Until recently,
      most variants reported have been identified in the clinical setting, which
      presumably bias described variants to pathogenic ones, as those found in the
      CYPAlleles database. Nevertheless, a large number of variants are being described
      in massive genome projects, many of which are found in dbSNP, but lack functional
      implications and/or their phenotypic effect. In this work, we gathered a total of
      1,340 GVs in the CYP21A2 gene, from which 899 variants were unique and 230 have
      an effect on human health, and compiled all this information in an integrated
      database. We also connected CYP21A2 sequence information to phenotypic effects
      for all available mutations, including double mutants in cis. Data compiled in
      the present work could help physicians in the genetic counseling of families
      affected with 21-hydroxylase deficiency.

PMID- 29035425
TI  - Inhaled versus systemic corticosteroids for the treatment of bronchopulmonary
      dysplasia in ventilated very low birth weight preterm infants.
AB  - BACKGROUND: This is an update of a review published in 2012. A related review
      "Inhaled versus systemic corticosteroids for preventing bronchopulmonary
      dysplasia in ventilated very low birth weight preterm neonates" has been updated
      as well. Bronchopulmonary dysplasia (BPD) is a serious and common problem among
      very low birth weight infants, despite the use of antenatal steroids and
      postnatal surfactant therapy to decrease the incidence and severity of
      respiratory distress syndrome. Due to their anti-inflammatory properties,
      corticosteroids have been widely used to treat or prevent BPD. However, the use
      of systemic steroids has been associated with serious short- and long-term
      adverse effects. Administration of corticosteroids topically through the
      respiratory tract may result in beneficial effects on the pulmonary system with
      fewer undesirable systemic side effects. OBJECTIVES: To compare the effectiveness
      of inhaled versus systemic corticosteroids administered to ventilator-dependent
      preterm neonates with birth weight <= 1500 g or gestational age <= 32 weeks after
      7 days of life on the incidence of death or BPD at 36 weeks' postmenstrual age.
      SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to
      search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue
      1), MEDLINE via PubMed (1966 to 23 February 2017), Embase (1980 to 23 February
      2017), and CINAHL (1982 to 23 February 2017). We also searched clinical trials
      registers, conference proceedings and the reference lists of retrieved articles
      for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA:
      Randomised or quasi-randomised controlled trials comparing inhaled versus
      systemic corticosteroid therapy (irrespective of dose and duration) starting
      after the first week of life in ventilator-dependent very low birth weight
      infants. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures
      expected by the Cochrane Collaboration. MAIN RESULTS: We included three trials
      that involved a total of 431 participants which compared inhaled versus systemic
      corticosteroids to treat BPD. No new trials were included for the 2017
      update.Although one study randomised infants at < 72 hours (N = 292), treatment
      started when infants were aged > 15 days. In this larger study, deaths were
      included from the point of randomisation and before treatment started. Two
      studies (N = 139) randomised and started treatment at 12 to 21 days.Two trials
      reported non-significant differences between groups for the primary outcome:
      incidence of death or BPD at 36 weeks' postmenstrual age among all randomised
      infants. Estimates for the largest trial were Relative risk (RR) 1.04 (95%
      Confidence interval (CI) 0.86 to 1.26), Risk difference (RD) 0.03 (95% CI -0.09
      to 0.15); (moderate-quality evidence). Estimates for the other trial reporting
      the primary outcome were RR 0.94 (95% CI 0.83 to 1.05), RD -0.06 (95% CI -0.17 to
      0.05); (low-quality evidence).Secondary outcomes that included data from all
      three trials showed no significant differences in the duration of mechanical
      ventilation or supplemental oxygen, length of hospital stay, or the incidence of
      hyperglycaemia, hypertension, necrotising enterocolitis, gastrointestinal bleed,
      retinopathy of prematurity or culture-proven sepsis moderate- to low-quality
      evidence).In a subset of 75 surviving infants who were enrolled from the United
      Kingdom and Ireland, there were no significant differences in developmental
      outcomes at seven years of age between groups (moderate-quality evidence). One
      study received grant support and the industry provided aerochambers and metered
      dose inhalers of budesonide and placebo for the same study. No conflict of
      interest was identified. AUTHORS' CONCLUSIONS: We found no evidence that inhaled
      corticosteroids confer net advantages over systemic corticosteroids in the
      management of ventilator-dependent preterm infants. There was no evidence of
      difference in effectiveness or adverse event profiles for inhaled versus systemic
      steroids.A better delivery system guaranteeing selective delivery of inhaled
      steroids to the alveoli might result in beneficial clinical effects without
      increasing adverse events.To resolve this issue, studies are needed to identify
      the risk/benefit ratio of different delivery techniques and dosing schedules for
      administration of these medications. The long-term effects of inhaled steroids,
      with particular attention to neurodevelopmental outcomes, should be addressed in
      future studies.

PMID- 29035423
TI  - Dementia Risk in Posttraumatic Stress Disorder: the Relevance of Sleep-Related
      Abnormalities in Brain Structure, Amyloid, and Inflammation.
AB  - PURPOSE OF REVIEW: Posttraumatic stress disorder (PTSD) is associated with
      increased risk for dementia, yet mechanisms are poorly understood. RECENT
      FINDINGS: Recent literature suggests several potential mechanisms by which sleep
      impairments might contribute to the increased risk of dementia observed in PTSD.
      First, molecular, animal, and imaging studies indicate that sleep problems lead
      to cellular damage in brain structures crucial to learning and memory. Second,
      recent studies have shown that lack of sleep might precipitate the accumulation
      of harmful amyloid proteins. Finally, sleep and PTSD are associated with elevated
      inflammation, which, in turn, is associated with dementia, possibly via cytokine
      mediated neural toxicity and reduced neurogenesis. A better understanding of
      these mechanisms may yield novel treatment approaches to reduce neurodegeneration
      in PTSD. The authors emphasize the importance of including sleep data in studies
      of PTSD and cognition and identify next steps.

PMID- 29035426
TI  - Synthesis of BSA-Coated BiOI@Bi2 S3 Semiconductor Heterojunction Nanoparticles
      and Their Applications for Radio/Photodynamic/Photothermal Synergistic Therapy of
      Tumor.
AB  - Developing an effective theranostic nanoplatform remains a great challenge for
      cancer diagnosis and treatment. Here, BiOI@Bi2 S3 @BSA (bovine serum albumin)
      semiconductor heterojunction nanoparticles (SHNPs) for triple-combination
      radio/photodynamic/photothermal cancer therapy and multimodal computed
      tomography/photoacoustic (CT/PA) bioimaging are reported. On the one hand, SHNPs
      possess strong X-ray attenuation capability since they contain high-Z elements,
      and thus they are anticipated to be a very competent candidate as radio
      sensitizing materials for radiotherapy enhancement. On the other hand, as a
      semiconductor, the as-prepared SHNPs offer an extra approach for reactive oxygen
      species generation based on electron-hole pair under the irradiation of X-ray
      through the photodynamic therapy process. This X-ray excited photodynamic therapy
      obviously has better penetration depth in bio-tissue. What's more, the SHNPs also
      possess well photothermal conversion efficiency for photothermal therapy, because
      Bi2 S3 is a thin band semiconductor with strong near-infrared absorption that can
      cause local overheat. In vivo tumor ablation studies show that synergistic
      radio/photodynamic/photothermal therapy achieves more significant therapeutic
      effect than any single treatment. In addition, with the strong X-ray attenuation
      and high near-infrared absorption, the as-obtained SHNPs can also be applied as a
      multimodal contrast agent in CT/PA imaging.

PMID- 29035427
TI  - Differences in the Korea Acute Myocardial Infarction Registry Compared with
      Western Registries.
AB  - The Korea Acute Myocardial Infarction Registry (KAMIR) is the first nationwide
      registry that reflects current therapeutic approaches and acute myocardial
      infarction (AMI) management in Korea. The results of the KAMIR demonstrated
      different risk factors and responses to medical and interventional treatments.
      The results indicated that the incidence of ST-elevation myocardial infarction
      (STEMI) was relatively high, and that the prevalence of dyslipidemia was
      relatively low with higher triglyceride and lower high-density lipoprotein
      cholesterol levels. Percutaneous coronary intervention (PCI) rates were high for
      both STEMI and non-ST-elevation myocardial infarction (NSTEMI) with higher use of
      drug-eluting stents (DESs). DES were effective and safe without increased risk of
      stent thrombosis in Korean AMI patients. Triple antiplatelet therapy, consisting
      of aspirin, clopidogrel, and cilostazol, was effective in preventing adverse
      clinical outcomes after PCI. Statin therapy was effective in Korean AMI patients,
      including those with very low levels of low-density lipoprotein cholesterol and
      those with cardiogenic shock. The KAMIR score had a greater predictive value than
      Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute
      Coronary Events (GRACE) scores for long-term mortality in AMI patients. Based on
      these results, the KAMIR will be instrumental for establishing new therapeutic
      strategies and effective methods for secondary prevention of AMI and guidelines
      for Asian patients.

PMID- 29035428
TI  - Initial Report of the Korean Organ Transplant Registry (KOTRY): Heart
      Transplantation.
AB  - BACKGROUND AND OBJECTIVES: The Korean Organ Transplant Registry (KOTRY), which
      was the first national transplant registry in Korea, was founded by the Korean
      Society for Transplantation and the Korean Center for Disease Control in 2014.
      Here, we present the initial report of the Korean Heart Transplant Registry.
      METHODS: A total of 183 heart transplantation (HTPL) patients performed at 4
      nationally representative hospitals were collected from April 2014 to December
      2015. We analyzed donor and recipient characteristics, treatment patterns, and
      immediate post-transplantation outcomes. RESULTS: One hundred and eighty-three
      patients were enrolled. The mean age of the patients was 50.5+/-13.5 years. The
      mean age of the male recipients was 4 years greater than that of the female
      recipients (51.7+/-13.3 years vs. 47.9+/-13.7 years, p<0.050). The mean age of
      donors was more than 12 years younger than that of heart recipients (37.6+/-10.1
      years). Dilated cardiomyopathy was the predominant cause (69%) of heart failure
      in recipients, followed by ischemic heart diseases (14%) and valvular heart
      disease (4%). Rejection episodes were most frequent in the 1-6-month period after
      transplantation (48%), and rarely required intensive treatment. Infection
      episodes were most frequent <1 month after transplantation (66%) and bacterial
      and viral infections were equally reported. The 1-year survival rate was 91.6%
      and most mortality cases occurred during the perioperative period within 1 month
      after transplantation. CONCLUSION: With the establishment of the KOTRY in 2014,
      it is now possible to present nationwide epidemiological data for HTPL in Korea
      for the first time. The KOTRY is the first national HTPL registry in Korea, and
      will continue until 2023.

PMID- 29035430
TI  - The Use Pattern and Clinical Impact of New Antiplatelet Agents Including
      Prasugrel and Ticagrelor on 30-day Outcomes after Acute Myocardial Infarction in
      Korea: Korean Health Insurance Review and Assessment Data.
AB  - BACKGROUND AND OBJECTIVES: Despite the favorable efficacy of new antiplatelet
      agents demonstrated in randomized controlled trials, their clinical implications
      in Korea are unclear. The purpose of this study was to investigate trends in
      antiplatelet agent use for acute myocardial infarction (AMI) and their impact on
      30-day clinical outcomes. METHODS: AMI patients undergoing percutaneous coronary
      intervention between 2010 and 2015 were assessed using claim data from the Health
      Insurance Review and Assessment Service. RESULTS: The use of new antiplatelet
      agents has rapidly increased since 2013 and has been preferred over clopidogrel
      (Plavix; Bristol-Myers Squibb/Sanofi Pharmaceuticals) since 2015. Both prasugrel
      (Effient; Eli Lilly and Company) (odds ratio [OR], 0.45; 95% confidence interval
      [CI], 0.31-0.67; p<0.001) and ticagrelor (Brilinta; AstraZeneca Pharmaceuticals
      LP) (OR, 0.84; 95% CI, 0.71-0.98; p=0.032) had an independent effect on lowering
      30-day mortality in a weighted multivariable logistic regression model. However,
      new antiplatelet agents had no significant effect on other clinical outcomes
      including myocardial infarction, stroke, bleeding, and readmission within 30
      days. CONCLUSION: The use of new antiplatelet agents is rapidly increasing, and
      they have been used more commonly than clopidogrel since 2015. We demonstrated
      that new antiplatelet agents have a favorable effect on reducing 30-day mortality
      in AMI patients in Korea.

PMID- 29035432
TI  - Unusual Disc Dislodgement of a Bjork-Shiley Valve after Long-term Implantation.

PMID- 29035429
TI  - Where Is the "Optimal" Fontan Hemodynamics?
AB  - Fontan circulation is generally characterized by high central venous pressure,
      low cardiac output, and slightly low arterial oxygen saturation, and it is quite
      different from normal biventricular physiology. Therefore, when a patient with
      congenital heart disease is selected as a candidate for this type of circulation,
      the ultimate goals of therapy consist of 2 components. One is a smooth adjustment
      to the new circulation, and the other is long-term circulatory stabilization
      after adjustment. When either of these goals is not achieved, the patient is
      categorized as having "failed" Fontan circulation, and the prognosis is dismal.
      For the first goal of smooth adjustment, a lot of effort has been made to
      establish criteria for patient selection and intensive management immediately
      after the Fontan operation. For the second goal of long-term circulatory
      stabilization, there is limited evidence of successful strategies for long-term
      hemodynamic stabilization. Furthermore, there have been no data on optimal
      hemodynamics in Fontan circulation that could be used as a reference for patient
      management. Although small clinical trials and case reports are available, the
      results cannot be generalized to the majority of Fontan survivors. We recently
      reported the clinical and hemodynamic characteristics of early and late failing
      Fontan survivors and their association with all-cause mortality. This knowledge
      could provide insight into the complex Fontan pathophysiology and might help
      establish a management strategy for long-term hemodynamic stabilization.

PMID- 29035433
TI  - Huge Fresh Mobile Thrombus Attached to the Descending Thoracic Aorta.

PMID- 29035431
TI  - Prognostic Application of Thoracic Aortic Calcium Scoring for Adverse Clinical
      Outcome Risk in Elderly Patients with Left Ventricular Hypertrophy.
AB  - BACKGROUND AND OBJECTIVES: Left ventricular hypertrophy (LVH) is associated with
      poor cardiovascular outcomes. Heavy aortic calcification exacerbates arterial
      stiffness, which consequently heightens left ventricular (LV) afterload. We
      assessed the usefulness of aortic calcification for predicting adverse
      cardiovascular outcomes and to determine whether the relationship, if any,
      differed as a function of LVH. METHODS: The analytic sample was comprised of a
      total of 487 individuals 65 years of age or older. Thoracic aorta calcium score
      (TACS) was measured by coronary computed tomography, and patients were stratified
      according to the median (TACS, 446 mm3). LVH obtained from echocardiography was
      defined as LV mass index >115 g/m2 for men and >95 g/m2 for women. Cox regression
      reporting hazard ratios (HRs) with 95% confidence intervals (CIs) was performed
      to predict the risk for the composite study endpoint, defined as cardiac death,
      admission for heart failure, obstructive coronary artery disease (CAD) requiring
      revascularization, or stroke. RESULTS: A total of 39 composite events (8.0%)
      occurred during a median follow-up of 65 months (interquartile range [IQR], 17-89
      months). For those with LVH, the concurrent presence of high TACS appeared to be
      an independent predictor (HR, 4.51; 95% CI, 1.71-11.88; p=0.002) for the
      composite study endpoint. Other combined LVH and TACS subgroups were not
      associated with significant factors for predicting the composite study endpoint
      (p>0.050, all). CONCLUSION: TACS provides robust predictive utility for a
      composite of cardiovascular events and cardiac death in persons with LVH. This
      finding was less pronounced in those with a relatively healthy myocardium,
      defined by the absence of LVH.

PMID- 29035434
TI  - Zebrafish Larvae Model of Dilated Cardiomyopathy Induced by Terfenadine.
AB  - BACKGROUND AND OBJECTIVES: Dilated cardiomyopathy can be the end-stage of severe
      cardiac disorders and directly affects the cardiac muscle, inducing cardiomegaly
      and heart failure (HF). Although a wide variety of animal models are available to
      study dilated cardiomyopathy, there is no model to assess dilated cardiomyopathy
      with non-invasive, simple, and large screening methods. METHODS: We developed a
      dilated cardiomyopathy model in zebrafish larvae using short duration
      terfenadine, a known cardiotoxic drug that induces ventricular size dilation.
      Fractional shortening of zebrafish hearts was calculated. RESULTS: We treated
      zebrafish with 5 to 10 MUM terfenadine for 24 hours. In terfenadine-treated
      zebrafish, blood frequently pooled and clotted in the chamber, and circulation
      was remarkably reduced. Atria and ventricles were swollen, and fluid was
      deposited around the heart, mimicking edema. Cardiac contractility was
      significantly reduced, and ventricular area was significantly enlarged. Heart
      rate was markedly reduced even after terfenadine withdrawal. Acridine orange
      staining also showed that terfenadine increased cardiomyocyte apoptosis. A
      significant increase of natriuretic peptide B (NPPB) mRNA was found in
      terfenadine-treated zebrafish. A low dose of terfenadine (5-10 MUM) did not show
      mortality in short-term treatment (24 hours). However, moderate dose (35-45 MUM)
      terfenadine treatment reduced zebrafish survival within 1 hour. CONCLUSION: With
      advantages of rapid sample preparation procedure and transparent observation of
      the live heart, this model can potentially be applied to large-scale drug
      screening and toxicity assays for non-ischemic HF.

PMID- 29035435
TI  - Clinical and Angiographic Outcomes of the First Korean-made Sirolimus-Eluting
      Coronary Stent with Abluminal Bioresorbable Polymer.
AB  - BACKGROUND AND OBJECTIVES: This trial evaluated the safety and efficacy of the
      Genoss drug-eluting coronary stent. METHODS: This study was a prospective,
      multicenter, randomized trial with a 1:1 ratio of Genoss drug-eluting stent
      (DES)TM and Promus ElementTM. Inclusion criteria were the presence of stable
      angina, unstable angina, or silent ischemia. Angiographic inclusion criteria were
      de novo coronary stenotic lesion with diameter stenosis >50%, reference vessel
      diameter of 2.5-4.0 mm, and lesion length <=40 mm. The primary endpoint was in
      stent late lumen loss at 9-month quantitative coronary angiography follow-up.
      Secondary endpoints were in-segment late lumen loss, binary restenosis rate,
      death, myocardial infarction (MI), target lesion revascularization (TLR), target
      vessel revascularization (TVR), and stent thrombosis during 9 months of follow
      up. RESULTS: We enrolled 38 patients for the Genoss DESTM group and 39 patients
      for the Promus ElementTM group. In-stent late lumen loss at 9 months was not
      significantly different between the 2 groups (0.11+/-0.25 vs. 0.16+/-0.43 mm,
      p=0.567). There was no MI or stent thrombosis in either group. The rates of death
      (2.6% vs. 0%, p=0.494), TLR (2.6% vs. 2.6%, p=1.000), and TVR (7.9% vs. 2.6%,
      p=0.358) at 9 months were not significantly different. CONCLUSION: This first-in
      patient study of the Genoss DESTM stent showed excellent angiographic outcomes
      for in-stent late lumen loss and major adverse cardiac events over a 9-month
      follow-up.

PMID- 29035437
TI  - Serum Uric Acid Levels and the Risk of Obesity: a Longitudinal Population-Based
      Epidemiological Study.
AB  - BACKGROUND: Obesity is a common chronic disease, and elevated serum uric acid has
      been suggested to be associated with obesity. However, whether the elevation is
      casual or a consequence of obesity remains unclear. We performed the study to
      investigate the longitudinal association between serum uric acid levels and
      obesity. METHODS: A total of 4411 initially obesity-free subjects were followed
      up for 9 years. The subjects were divided into groups according to the serum uric
      acid quartile. Univariable and multivariable Cox regression models were used to
      analyze the risk factors for the development of obesity. RESULTS: Of the 4411
      subjects, 1272 (28.8%) subjects developed obesity over 9 years of follow-up. The
      cumulative incidence of obesity was 21.7%, 26.4%, 31.0%, and 36.4% in quartile 1,
      2, 3 and 4, respectively (p for trend < 0.001). Cox regression analyses indicated
      that serum uric acid levels were independently and positively associated with the
      risk of incident obesity. CONCLUSIONS: Our longitudinal study demonstrated that
      high serum uric acid levels increase the risk of obesity.

PMID- 29035436
TI  - Cardioprotective Effect of the SDF-1alpha/CXCR4 Axis in Ischemic Postconditioning
      in Isolated Rat Hearts.
AB  - BACKGROUND AND OBJECTIVES: Information about the role of the stromal cell-derived
      factor-1alpha (SDF-1alpha)/chemokine receptor type 4 (CXCR4) axis in ischemic
      postconditioning (IPOC) is currently limited. We hypothesized that the SDF
      1alpha/CXCR4 signaling pathway is directly involved in the cardioprotective
      effect of IPOC. METHODS: Isolated rat hearts were divided into four groups. The
      control group was subjected to 30-min of regional ischemia and 2-hour of
      reperfusion (n=12). The IPOC group was induced with 6 cycles of 10-second
      reperfusion and 10-second global ischemia (n=8) in each cycle. The CXCR4
      antagonist, AMD3100, was applied before reperfusion in the IPOC group (AMD+IPOC
      group, n=11) and control group (AMD group, n=9). Hemodynamic changes with
      electrocardiography were monitored and infarct size was measured. The SDF-1alpha,
      lactate dehydrogenase (LDH) and creatine kinase (CK) concentrations in perfusate
      were measured. We also analyzed extracellular signal-regulated kinase 1/2
      (ERK1/2) and Akt phosphorylation state expression. RESULTS: IPOC significantly
      reduced infarct size, but AMD3100 attenuated the infarct reducing effect of IPOC.
      IPOC significantly decreased LDH and CK, but these effects were reversed by
      AMD3100. ERK1/2 and Akt phosphorylation increased with IPOC and these effects
      were blocked by AMD3100. CONCLUSION: Based on the results of this study, SDF
      1alpha/CXCR4 signaling may be involved in IPOC cardioprotection and this
      signaling pathway couples to the ERK1/2 and Akt pathways.

PMID- 29035439
TI  - Mean Platelet Volume in Patients with Increased Cardiac Troponin I.

PMID- 29035438
TI  - High-Throughput Screening of Escherichia coli O157:H7 Pathogenic Genes via
      Pathway Enrichment and Operon Analysis.
AB  - BACKGROUND: About thirty thousand people globally die every day from infectious
      diarrhea, mostly caused by pathogenic Escherichia coli (E. coli) O157:H7.
      METHODS: In order to search for clinical diagnostic biomarkers and novel drug
      targets for infectious diarrhea, we used a bibliometric method to collect
      pathogenic genes of E. coli O157:H7 and performed a functional analysis of the
      important pathogenic genes by pathway enrichment and operon analysis. RESULTS: We
      found 364 pathogenic genes which may be involved in infection with E. coli
      O157:H7 including 50 new specific pathogenic genes. It is possible that these
      newly found pathogenic genes will be of great importance in the treatment of E.
      coli O157:H7 infected diseases and the discovery of novel diagnostic biomarkers.
      CONCLUSIONS: Our findings also lay a theoretical foundation for the control,
      diagnosis, and prognosis of pathogenic E. coli related diseases.

PMID- 29035440
TI  - Impact of pH on Urine Chemistry Assayed on Roche Analyzers.
AB  - BACKGROUND: The pH may impact the concentration of certain urinary parameters,
      making urine pre-treatment questionable. METHODS: 1) Determining the impact of pH
      in vitro on the urinary concentration of chemistry parameters assayed on Roche
      Modular analyzers. 2) Evaluating whether concentrations depended on pH in non
      pretreated urines from patients. RESULTS: 1) The optimal urinary pH values for
      each measurement were: 6.3 +/- 0.8 (amylase), < 5.5 (calcium and magnesium), <
      6.5 (phosphorus), > 6.5 (uric acid). Urinary creatinine, sodium and urea
      concentrations were not pH-dependent. 2) In urines from patients, the pH was
      negatively associated with the concentration of some urinary parameters. However,
      concentrations of all the parameters were strongly and positively correlated with
      urinary creatinine, and relationships with pH were no longer evidenced after
      creatinine-normalization. CONCLUSIONS: The need for urine pH adjustment does not
      seem necessary when considering renal function. However, from an analytical and
      accreditation standpoint, the relationship between urine pH and several
      parameters justifies its measurement.

PMID- 29035441
TI  - Eubacterium moniliforme Bacteremia in a Woman with Fractures.
AB  - E. moniliforme infections in humans have not been reported previously. We firstly
      described blood-stream infections caused by E. moniliforme in an elder woman with
      fractures of her left thigh. This study highlights the strategies to detect this
      anaerobic pathogen and the importance of investigating its molecular epidemiology
      in humans.

PMID- 29035442
TI  - Long Noncoding RNA PVT1 as a Potent Predictor of Prognosis in Cancers: a Meta
      Analysis.
AB  - BACKGROUND: Plasmacytoma variant translocation 1 (PVT1), an oncogenic long
      noncoding RNA located in a recognized cancer-risk gene region-8q24, is
      significantly overexpressed in various cancers. Many studies have found that high
      expression of PVT1 was correlated with poor prognosis. METHODS: This meta
      analysis was performed by searching electronic databases Pubmed, Web of Science,
      Chinese National Knowledge Infrastructure, WanFang, and ChongQing VIP for
      eligible papers on the prognostic impact and clinicopathological characteristics
      of PVT1 expression in cancer from inception to January 31, 2017. The hazard ratio
      (HR) and odds ratio (OR) with 95% confidence intervals (CI) were computed to
      estimate the pooled effect of PVT1 on prognosis of cancers using Stata 12.0
      version software. RESULTS: Thirteen studies were finally included in this review
      with a total of 1559 patients. The pooled result indicated that overexpressed
      PVT1 predicts a poorer prognosis of cancerous patients for overall survival (HR =
      1.91, 95% CI: 1.61 - 2.26, p < 0.001) and disease-free survival (HR = 1.90, 95%
      CI: 1.46 - 2.48, p < 0.001) or recurrencefree survival (HR = 1.77, 95% CI: 1.24 -
      2.52, p = 0.002) or progression-free survival (HR = 2.84, 95% CI: 1.67 - 4.82, p
      < 0.001). High expression of PVT1 was closely associated with tumor-node
      metastasis (TNM) stage (III/IV vs. I/II: OR = 3.19, 95% CI: 2.43 - 4.18, p <
      0.001), and the significant correlation between PVT1 expression and TNM stage is
      found in T classification (T3/4 vs. T1/2: OR = 6.48, 95% CI: 2.93 - 14.31, p <
      0.001) and lymph node metastasis (present vs. absent: OR = 2.56, 95% CI:1.36 -
      4.80, p = 0.003), but not in distant metastasis of patients with cancers (yes vs.
      no: OR = 2.50, 95% CI: 0.72 - 8.66, p = 0.15). Furthermore, the cancerous
      patients with high PVT1 expression had a worse histological differentiation than
      those with low PVT1 expression (undifferentiated/poorly vs. moderately/well: OR =
      1.48, 95% CI: 1.02 - 2.14, p = 0.039). CONCLUSIONS: PVT1 could serve as a potent
      predicator of prognosis in different types of cancers.

PMID- 29035443
TI  - Genetic Variants of Pre-microRNAs A-499G(rs3746444) and T-196a2C(rs11614913) with
      Ulcerative Colitis (UC) and Investigated with Thiopurine-S-Methyltransferase
      (TPMT) Activity.
AB  - BACKGROUND: Abnormal expression and different splicing of miRNAs are involved in
      several human inflammatory disorders. It has been suggested that gene variants of
      miRNAs may be associated with increased risk of ulcerative colitis (UC). We aimed
      to evaluate the association of two SNPs (miRNA-A-499G(rs3746444) and miRNA
      T196a2C(rs11614913)) with the risk of UC and monitor their effect on thiopurine-S
      methyltransferase (TPMT) activity in Kurdish population of Iran. METHODS: This
      case-control study was performed on 210 UC patients and 212 healthy individuals.
      Genotyping assay was performed using PCR-RFLP and the TPMT-activity was measured
      via non-extraction-HPLC method. RESULTS: We found that the existence of GG
      genotypes and G allele of miRNA-A-499G SNPs significantly increased the risk of
      UC by 1.76 and 1.32 times, respectively. The distribution of GG genotype (23.8%
      vs. 16%, chi2 = 4.2, p = 0.041) and G allele (46.4% vs. 39.4%, chi2 = 4, p =
      0.046) of miRNA-A-499G, were significantly higher in UC patients compared to
      control group. Our results indicate that miRNA SNPs (miRNA-T-196a2C and miRNA-A
      499G) have no significant effect on TPMT activity of studied population.
      CONCLUSIONS: Our results, for the first time, demonstrate that the GG genotype
      and G allele of miRNA-A-499G significantly increase the risk of UC. However,
      miRNA SNPs showed no significant effect on TPMT activity in studied population.

PMID- 29035444
TI  - Circulating microRNAs Expressions as Genetic Biomarkers in Pancreatic Cancer
      Patients Continuous Non-Invasive Monitoring.
AB  - BACKGROUND: Pancreatic cancer is one of the most important causes of death
      worldwide. The main cause is late detection. Also, an important factor playing a
      role in altering the clinical status of these patients is the lack of methods for
      the evaluation of therapeutic response. A marker that can be useful, both in
      early diagnosis and in evaluating and monitoring non-invasive treatment response,
      is analyzing the expression of miRNAs. In this paper, we summarize genetic and
      epigenetic aspects of miRNAs in pancreatic cancer. Moreover, we want to emphasize
      potential miRNAs expressions that can be used as biomarkers for the management of
      patients with pancreatic cancer. METHODS: Studies available in scientific
      databases, such as PubMed and Scopus, were analyzed for conducting the present
      study. The keywords "miRNAs expression", "pancreatic cancer", and "genetic
      biomarkers" were used in the search engine. RESULTS: Following the searches, 187
      primary scientific articles were analyzed. After rigorous analysis 40 articles
      were selected for the study. A high percentage of papers highlight the importance
      of using microRNAs as modern, non-invasive, and accurate biomarkers, designed for
      the early diagnosis and continuous monitoring of both the clinical outcome and
      treatment response of the patient. CONCLUSIONS: The expression of miRNAs can be
      successfully used for the evaluation and non-invasive monitoring of patients with
      pancreatic cancer.

PMID- 29035445
TI  - Expression of Leukocytic Syncytin-1 in B-Cell Acute Lymphoblastic Leukemia and
      Acute Myeloid Leukemia Patients.
AB  - BACKGROUND: Syncytin-1 is improperly expressed in several cancers. However, its
      expression profile across leukocytes in leukemia patients has not yet been
      analyzed. METHODS: A total of 50 AML cases and 14 B-cell ALL patients were
      consecutively recruited. Bone marrow samples were subjected to flow cytometry.
      Statistical analysis was applied to compare syncytin-1 expression between B-cell
      ALL and AML across granulocytes, leukemia cells, and T-lymphocytes (including
      CD3+, CD4+, and CD8+ subsets thereof) and to correlate syncytin-1 expression to
      leukemia cells and lymphocytes with the T-cell subset percentages. RESULTS: The
      syncytin-1-expressing leukemia cell% in AML patients was significantly higher
      than that in B-cell ALL patients (p < 0.05). The CD8+ T-cell% in AML patients was
      significantly higher than that in B-cell ALL patients (p < 0.05). The syncytin-1
      expression rate on leukemia cells was positively correlated with the CD8+ T-cell
      percentage (r = 0.289, p < 0.05), while the syncytin-1 expression rate on
      lymphocytes was negatively correlated with the CD3+, CD4+, and CD8+ T-cell
      percentages (r = -0.273, -0.450, and -0.307, respectively; p < 0.05).
      CONCLUSIONS: The percentage of syncytin-1-expressing leukemia cells in AML - due
      to its positive correlation with the CD8+ suppressor T-cell percentage - shows
      potential as an indicator of poorer long-term immunity in AML patients.

PMID- 29035446
TI  - The Effects of Insulin and Glucose on Different Characteristics of a UPEC:
      Alterations in Growth Rate and Expression Levels of some Virulence Genes.
AB  - BACKGROUND: Host factors are known to modulate virulence, antibiotic
      susceptibility, and growth rate of bacteria. The effect of human insulin and
      glucose on growth rate and expression of virulence genes (usp, sfa/foc, cnf1) of
      a uropathogenic E. coli (UPEC) strain were investigated in this study. METHODS:
      E. coli C7 was grown in tryptic soy broth (TSB-control) and TSB containing 20
      uU/mL insulin, 200 uU/mL insulin, 0.1% glucose, and 200 uU/mL insulin + 0.1%
      glucose. Growth rates were determined via optical density measurement in a
      spectrophotometer. Real-time polymerase chain reaction was used to determine the
      gene expression levels. Statistical analyses were performed via Tukey's post hoc
      test. RESULTS: Differences were found to be not statistically significant for
      bacterial growth rate in TSB and TSB with insulin and/or glucose. The expression
      levels of all three virulence genes were shown to be reduced significantly in the
      presence of insulin and/or glucose. The highest degree of repression was observed
      in 200 uU/mL insulin added to TSB. Also, the repression level of the gene
      expression was revealed to be reduced in 0.1% glucose supplemented TSB.
      CONCLUSIONS: In the present study, it was shown that insulin and glucose can
      modulate UPEC's gene expression while the growth rate was not affected.

PMID- 29035447
TI  - Porphyromonas gingivalis Infection Accelerates Atherosclerosis Mediated by
      Oxidative Stress and Inflammatory Responses in ApoE-/- Mice.
AB  - BACKGROUND: The periodontal pathogen Porphyromonas gingivalis (P. gingivalis) has
      been proven to accelerate the development of atherosclerosis in apolipoprotein E
      (ApoE)-deficient mice. In this study, we used an ApoE knockout (ApoE-/-) mouse
      model with chronic intravenous infection with P. gingivalis to investigate the
      possible mechanisms of P. gingivalis-induced atherosclerosis. METHODS: Eight-week
      old ApoE-/- mice were randomly assigned to two groups: (a) ApoE-/- + PBS (n = 8);
      (b) ApoE-/- + P. gingivalis (n = 8). Both of the groups received intravenous
      injections 3 times per week. After 4 weeks, oxidative stress mediators in serum,
      heart, aorta, and liver tissues were analyzed by using histology, ELISA, realtime
      PCR, and Western blot. RESULTS: Development of atherosclerosis as plaque
      formation in the aorta has been confirmed upon P. gingivalis infection. An
      abnormal lipid profile was found in the serum (increased amounts of very low
      density lipoprotein [vLDL] and oxidized low-density lipoprotein [oxLDL], and
      decreased amount of HDL) and in some organs including heart, aorta or liver
      (increased mRNA levels of oxidized low-density lipoprotein receptor-1 [LOX-1] or
      fatty acid synthase [FAS]). Meanwhile, aggravated oxidative stress (higher level
      of reactive oxygen species [ROS] in the serum, and increased mRNA levels of
      nicotinamide adenine dinucleotide phosphate oxidase [NOX]-2 and/or NOX-4 in the
      three organs) was observed, as well as enhanced inflammatory responses (increased
      expression and secretion of C-reactive protein [CRP] in the liver and serum, and
      increased mRNA levels of cyclooxygenase-2 [NOX-2] and/or inducible nitric oxide
      synthase [iNOS] in the three organs). Besides, inflammatory mediators including
      nuclear factor of kappa B (NF-kappaB) and iNOS showed increased protein levels in
      the three organs after P. gingivalis infection. CONCLUSIONS: These results
      suggest that chronic intravenous infection with P. gingivalis in ApoE-/- mice
      could accelerate the development of atherosclerosis, possibly associated with
      mediating oxidative stress as well as inflammatory responses and disturbing the
      lipid profile.

PMID- 29035448
TI  - A Case Study in Advanced Lung Cancer Patients with Vimentin Over Expression.
AB  - BACKGROUND: Vimentin belongs to an intermediate filament (IF) family of proteins,
      mainly present in mesenchymal cells and has a crucial role in maintaining
      cellular integrity. Vimentin can induce epithelial to mesenchymal transition, and
      thus increase migration and invasion capacity of the cells. It has been shown to
      be a useful and reliable diagnostic and prognostic marker in several cancers
      including colon cancers, breast and hepatocellular cancers. Recent studies
      suggest that it may have a role in distant metastasis of non-small cell lung
      cancer (NSCLC) accounting for poor survival [1]. METHODS: The aim of the study is
      to assess the impact of vimentin testing as a diagnostic and prognostic marker in
      NSCLC. This is a case study of 12 NSCLC patients who had vimentin testing as a
      part of their work up over the past five years at the University of Cincinnati. A
      total of 12 patients with advanced lung cancer were included in this case study
      as they were found to have strong vimentin expression. This was correlated with
      overall survival of this group of patients. RESULTS: Median survival of the
      patients was 4.66 months. This is 7.34 months less compared to the median
      survival of patients with stage IV NSCLC which is reported to be 12 months.
      CONCLUSIONS: More studies are warranted into the use of vimentin as an emerging
      useful marker for early diagnosis, aggressive transformation relapse, and
      prognostication of NSCLC. It may have therapeutic value in NSCLC as observed in
      other cancers.

PMID- 29035449
TI  - Performance Verification of the Iris iQ200 Sprint Automated Urine Microscopy
      Analyzer in a Hospital Routine Laboratory.
AB  - BACKGROUND: Systematic performance verification is required before a laboratory
      can introduce a new measurement procedure for reporting results of patient
      testing. The aim of this study was to determine whether a new Iris iQ200 Sprint
      automated urine microscopy analyzer (iQ200 Sprint) could be incorporated into our
      routine laboratory. METHODS: A total of 421 fresh urine samples were selected
      from the Affiliated Hospital of Nantong University, including those from healthy
      individuals and those with a variety of abnormalities to ensure a wide range of
      results. Precision, recovery, carry-over, linearity and reference interval were
      verified according to well-established protocols. RESULTS: The repeatability
      studies found coefficients of variability (CVs) in the range of 10.53% - 20.28%
      for red blood cells, white blood cells, and squamous epithelial cells, while the
      CV for the iQ Positive Control sample was 3.23%. The relative bias was 0.5% for
      the iQ Positive Control sample and no carry-over was detected. Linearity was
      observed at concentrations of 10 - 2069.5 particles/MUL (y = 0.989x + 9.1, R2 =
      0.999). The manufacturer's claimed reference interval meets the requirements for
      medical usefulness. CONCLUSIONS: Performance verification is needed before a
      clinical laboratory can introduce a new measurement procedure. The iQ200 Sprint
      is sufficiently precise and reliable to be applied in our clinical laboratory.

PMID- 29035450
TI  - Imbalance between Matrix Metalloproteinases and Tissue Inhibitors of
      Metalloproteinases Promotes Invasion and Metastasis of Head and Neck Squamous
      Cell Carcinoma.
AB  - BACKGROUND: The balance between collagenolysis and its inhibition is critical
      during extracellular matrix remodeling in head and neck squamous cell carcinoma
      (HNSCC). An imbalance between matrix metalloproteinases (MMPs) and their tissue
      inhibitors (TIMPs) plays a critical role in the development of tumor cell
      invasion and metastasis. The purpose of the study was to determine MMP-9/TIMP-1
      and MMP-2/TIMP-2 ratios in the sera of patients with HNSCC in relation to
      clinicopathological parameters. METHODS: Serum samples from seventy patients with
      HNSCC were measured by ELISA, before and 2 days after surgery. Forty healthy
      volunteers were selected as controls. RESULTS: Preoperative MMP-9/TIMP-1 and MMP
      2/TIMP-2 ratios were significantly higher in HNSCC patients than in the control
      group (p < 0.001 and p = 0.002, respectively). Changes in MMP-9 concentration and
      MMP9/TIMP-1 ratio after surgery had a negative correlation with lymph node
      involvement (r = - 0.35, p = 0.021 and r = - 0.37, p = 0.013), while changes in
      TIMP-1 had a positive one (r = 0.45, p = 0.006). Histological grade was
      positively correlated with the changes in circulating TIMP-2 level (r = 0.39, p =
      0.021). No significant correlation was discovered between MMP-2/TIMP-2 ratio and
      tumor grade or any clinicopathological variables. CONCLUSIONS: Our results
      suggest that an imbalance between MMP-9 and TIMP-1 could play an important role
      in metastatic spread via lymphatic pathways of HNSCC cells. MMP-9/TIMP-1 ratio
      and, in particular, MMP-9, TIMP-1, TIMP-2, may represent suitable biomarkers for
      early diagnosis and detection of disease progression and dissemination in HNSCC
      patients.

PMID- 29035451
TI  - Investigations of the Serum Free Light Chain Ratio According to the Updated 2014
      IMWG Diagnostic Criteria for Multiple Myeloma in Korean Patients with Newly
      Diagnosed Multiple Myeloma.

PMID- 29035452
TI  - Role of Cytokines in the Pathogenesis of Visceral Leishmaniasis.
AB  - Infection in humans with Leishmania manifests into a spectrum of diseases. The
      manifestations of the disease depend on the resultant evasion of the parasite to
      immune responses namely macrophages, which is an exclusive host of leishmania.
      The B cells valiantly mount antibody responses, however to no avail as the
      Leishmania parasites occupy the intracellular niches of the macrophages.
      Extensive studies have been documented on the role of cell-mediated immunity
      (CMI) in protection and counter survival strategies of the parasites leading to
      down-regulation of CMI. The present review attempts to discuss the cytokines in
      progression or resolution of visceral form of leishmaniasis or kala-azar,
      predominantly affecting the Indian subcontinent. The components/cytokine(s)
      responsible for the regulation of the critical balance of Th1/Th2/Th9/Th17/Treg
      cells has been discussed in the perspective. Therefore, any strategy involving
      the treatment of VL needs to consider the balance and regulation of CD4+ T cell
      function.

PMID- 29035453
TI  - Immunophenotyping of Chronic Lymphocytic Leukemia.
AB  - BACKGROUND: Chronic Lymphocytic Leukemia (CLL) is one of the most common
      diagnoses made by flow cytometry laboratories. There is no consensus on which
      markers need to be used in flow cytometry for accurate immunophenotyping. Herein,
      we investigated the role of markers used in flow cytometry in the distinction
      between CLL and MCL. METHODS: A total 339 recently diagnosed B
      lymphoproliferative patient cases were retrospectively studied for their
      immunophenotypical propoerties using flow cytometry. They included 306 CCL cases
      and 33 MCL cases. RESULTS: The positivity of CD23 was diagnostic for CLL (p <
      0.001). CD22, CD79b, and FMC7 expressions were highly positive in CLL cases, but
      not statistically significant in making differential diagnoses between atypical
      CLL and MCL (p = 1.000, p = 0.431 and p = 1.000, respectively). Evaluation of
      CD11c, CD25, CD43, and CD38 expressions, which are included in the LPD panel but
      not in the matatutes scoring, revealed that CD11c, CD38, and CD43 expressions are
      statistically significant in the distinction of atypical CLL from MCL (p < 0.001,
      p < 0.001, and p < 0.001). CONCLUSIONS: We can say that CD11c, CD38, and CD43,
      which have been included in our lymphoproliferative disease panel, were more
      valuable than CD22, CD79b, and FMC7 in the diagnosis of CLL.

PMID- 29035454
TI  - The Relationship Between MDM2 T309G Polymorphism and Leukemia in the Chinese
      Population: Evidence from a Meta-Analysis.
AB  - BACKGROUND: Increasing numbers of studies have been carried out on the
      association of MDM2 T309G polymorphism with susceptibility to leukemia and have
      generated conflicting results. This meta-analysis updated and revaluated the
      possible associations between MDM2 T309G polymorphism and leukemia in the Chinese
      population. METHODS: The PubMed, Springer Link, Ovid, Chinese Wanfang Data
      Knowledge Service Platform, Chinese National Knowledge Infrastructure, and
      Chinese Biology Medicine were searched up to February 2017. Fixed-effect and
      random-effect meta-analytical techniques were conducted for the outcome measure
      and subgroup analyses. RESULTS: Overall, the meta-analysis demonstrated
      significant associations between the MDM2 T309G polymorphism and increased risk
      for leukemia in the Chinese population. Subgroup analyses indicated similar
      results in South China. As for subgroup analysis by clinical types, data
      suggested increased risk for chronic myeloid leukemia (CML). CONCLUSIONS: Our
      study suggested that MDM2 T309G polymorphism might be a low-penetrant risk factor
      for leukemia among Chinese.

PMID- 29035455
TI  - Evaluation of a Magnetic Cellulose-Based DNA Extraction System to Improve the
      Performance of HybriBio Human Papillomavirus Genotyping and Screening Tests for
      Cervical Swab Samples.
AB  - BACKGROUND: To ensure the accuracy of clinical human papillomavirus (HPV)
      testing, the nucleic acid extraction procedure should be thoroughly evaluated for
      each clinical sample type. Therefore, we evaluated whether the MagCore(r)
      Automated Nucleic Acid Extraction system (MagCore system) could improve HybriBio
      HPV test performance for cervical swab samples. METHODS: We compared the
      performance of HybriBio HPV genotyping and screening tests using samples prepared
      with the MagCore system and Cell Lysis Kit, which was provided by the HPV test
      manufacturer. RESULTS: The MagCore system extracted high quality DNA and
      outperformed the Cell Lysis Kit in the subsequent analysis. In terms of the HPV
      genotyping testing, use of the MagCore system-extracted DNA markedly increased
      the signal intensity compared to that of DNA extracted with the Cell Lysis Kit
      for low concentrations of HPV DNA. Thus, the analytical sensitivity of testing
      was increased approximately 10 times by using the MagCore system, and the
      reproducibility was also increased (97.1% vs. 88.2%). In terms of the HPV
      screening tests, use of the MagCore system improved the compatibility of the
      internal control and targets, reducing the risk of false or invalid results. The
      MagCore system also improved the amplification efficiency and quantification
      accuracy for HPV16 detection. CONCLUSIONS: We demonstrated that the performance
      of HybriBio HPV genotyping and screening tests can be improved by using the
      MagCore system. This study not only provided an alternative, robust DNA
      extraction method for clinical users but also reemphasized the importance of
      establishing a reliable DNA extraction procedure for clinical HPV testing.

PMID- 29035456
TI  - Circulating miR-29b and miR-424 as Prognostic Markers in Patients with Acute
      Cerebral Infarction.
AB  - BACKGROUND: Down-regulation of miR-29b and miR-424 have been observed in patients
      with acute cerebral infarction (ACI); however, the clinical significance of
      circulating miR-29b and miR-424 as prognostic markers still requires further
      investigation. METHODS: A total of 45 patients diagnosed with ACI and 45 healthy
      volunteers were enrolled in this study, and the clinical information of the
      patients were collected. The serum samples of the participants were collected and
      stored at -80 degrees C. The relative expression of miR-29b and miR-424 was
      determined using RT-qPCR, and the serum levels of IL-6, IL-4, TNF-alpha, and IFN
      gamma were measured using an enzyme-linked immunosorbent assay (ELISA) kits. The
      short-term prognosis of patients was evaluated using the Glasgow Outcome scale
      (GOS) at day 30. RESULTS: The serum levels of miR-29b and miR-424 were
      significantly lower in patients with ACI compared with the healthy controls (p <
      0.01) and the serum level of IL-6, IL-4, and TNF-alpha were significantly up
      regulated in patients with ACI (p < 0.05); moreover, using the Glasgow Outcome
      scale (GOS) as a prognostic index, it has been proved that the serum level of
      both miR-29b and miR-424 were positively associated with the short-term prognosis
      of the patients; finally, the expression of the circulating miR-29b and miR-424
      were negatively correlated with the serum level of IL-6, IL-4, and TNF-alpha.
      CONCLUSIONS: Lower levels of circulating miR-29b and miR-424 in patients with
      acute cerebral infarction may predict poor prognosis, and the expression of
      circulating miR-29b and miR-424 are negatively correlated with the serum level of
      some pro-inflammatory cytokines, suggesting that circulating miR-29b and miR-424
      may have the potential to become prognostic markers and therapeutic targets for
      the management of acute cerebral infarction.

PMID- 29035458
TI  - Concordance of Mutation Detection in Circulating Tumor DNA in Early Clinical
      Trials Using Different Blood Collection Protocols.
AB  - BACKGROUND: Small fragments of tumor DNA can be found in the circulation of
      cancer patients, providing a noninvasive access to tumor material (liquid
      biopsy). Analysis of circulating tumor DNA (ctDNA) has been used for diagnosis,
      treatment decisions, and detection of therapy resistance, including in patients
      with tumors inaccessible for biopsy, making ctDNA an important alternative source
      of tumor material. Immediate separation of plasma is widely used in standard
      isolation of cell-free DNA to ensure high quality plasma DNA. However, these
      procedures are labor intensive and logistically challenging in a clinical
      setting. Here we investigate the concordance between standard blood collection
      for molecular analysis using immediate separation of plasma, compared to the use
      of collection tubes allowing for delayed processing. METHODS: In this study, we
      measured the fractional abundance of tumor specific mutations (BRAF p.V600E and
      PIK3CA p.H1047R) in ctDNA isolated from blood samples collected in either cell
      stabilizing Cell-Free DNA BCT tubes (delayed processing within 72 hours) or
      standard K3EDTA tubes (immediate processing within 15 minutes). Twenty-five blood
      sample pairs (EDTA/BCT) were collected from patients with advanced solid cancers
      enrolled in early clinical trials. RESULTS: Concordance in the fractional
      abundance of mutations in ctDNA isolated from blood collected in either K3EDTA or
      BCT tubes from patients with different solid cancers was observed. CONCLUSIONS:
      This study indicates that BCT tubes are preferable for collection of circulating
      DNA in a clinical setting due to the favorable storage and shipping conditions.

PMID- 29035457
TI  - Evaluation of mir-203 Expression Levels and DNA Promoter Methylation Status in
      Serum of Patients with Endometrial Cancer.
AB  - BACKGROUND: Endometrial cancer (EC) is currently considered the fourth most
      frequent female cancer in Europe. In an attempt to achieve an early diagnosis,
      many studies have identified some putative biomarkers for gynecologic cancers,
      including circulating microRNAs (miRs) and aberrant promoter methylation status.
      Previous studies which have investigated miR-203 expression profiles in EC
      tissues and normal endometrial tissues concluded that miR-203 is regulated by
      methylation promoter. The aim of this study was to investigate the expression of
      miR-203 and promoter methylation levels in serum of EC patients and healthy
      controls (HC). METHODS: Forty-five EC patients (64 +/- 12 years) and 30 HC (63 +/
      13 years) were enrolled before undergoing therapeutic procedures. RNA extraction
      from serum was performed with mirVana PARIS Isolation Kit (Thermo Scientific).
      miR expression was assessed by quantitative RT-PCR (Applied Biosystems). The
      expression levels of miR were normalized to miR-16 and calculated using the 2
      DeltaCt method. A quantitative methylation-specific PCR (MSP) technique was used
      to analyze miR-203 promoter methylation status. Differences between groups were
      assessed by Mann-Whitney test (for continuous variables) and chi-squared test
      (for categorical variables), whereas the correlation was calculated using
      Spearman's test. The diagnostic performance of miR-203 was defined using receiver
      operator characteristic (ROC) curves. RESULTS: Serum expression levels of miR-203
      were higher in EC patients compared to HC (p = 0.002). Aberrant miR-203
      methylation was detected in 11/45 (24.4%) EC patients and in 2/30 (6.6%) HC (p =
      0.046). The expression levels of miR-203 were not significantly correlated with
      promoter methylation status. The area under the curve of miR-203 expression was
      0.71 (p = 0.002). CONCLUSIONS: The high circulating miR-203 expression levels in
      EC patients compared to HC confirm the role of this miR as a potential biomarker
      for diagnosis of EC. Aberrant miR-203 methylation assessed in the peripheral
      blood does not apparently reflect cancer biology.

PMID- 29035459
TI  - Level of Platelet Distribution Width and Outcome Prediction in Patients with
      Traumatic Brain Injury.
AB  - BACKGROUND: This study examines the clinical utility of the level of increased
      platelet distribution width (PDW) as a predictor of outcome in patients with
      traumatic brain injury. METHODS: In this retrospective study, 120 patients with
      traumatic brain injury (TBI) were recruited. Age, gender, PDW, and Glasgow Coma
      Scale (GCS) scores were measured. These patients were divided into two groups
      based on their 30-day outcomes. Receiver operating curves (ROCs) were generated
      to identify predictors of 30-day mortality. RESULTS: One hundred twenty patients
      with traumatic brain injury were enrolled in this study, 89 males (74.2%) and 31
      females (25.8%) with a median age of 49.5 (19 - 89) years. The in-hospital
      mortality rate was 10.8% (n = 13). PDW levels in non-surviving patients were
      higher than in surviving patients. The higher the PDW, the lower the GSC score.
      The area under the curve (AUC) for PDW levels with regard to predicting 30-day
      mortality was 0.88 (95% confidence interval (CI), 0.78 to 0.97; p < 0.001). There
      was correlation between PDW level and GCS score (r = -0.30, 95% confidence
      interval (CI), - 0.46 to - 0.13; p < 0.001). CONCLUSIONS: PDW levels were
      associated with injury severity and mortality in patients with severe TBI.

PMID- 29035460
TI  - Pleural Alveolar Rhabdomyosarcoma.
AB  - Alveolar rhabdomyosarcoma (ARMS) commonly occurring in children and adolescents,
      is a rare and aggressive soft tissue malignancy. Here, a rare case of pleural
      ARMS is reported in a boy presenting dyspnea for two weeks. The pathology of a
      biopsy specimen from pleura showed ARMS. PAX3-FKHR fusion protein is positive and
      the PAX7-FKHR fusion protein is negative as detected by fluorescence in situ
      hybridization. The prognosis of this patient was poor and nonresponsive to
      chemotherapy.

PMID- 29035461
TI  - Evaluating EFEMP1 in Cerebrospinal Fluid and Serum as a Potential Diagnosis
      Biomarker for Meningiomas.
AB  - BACKGROUND: The aim of this study was to determine the cerebrospinal fluid (CSF)
      and serum levels of EGF containing fibulin-like extracellular matrix protein 1
      (EFEMP1) in the patients with meningiomas and explore its potential as a
      biomarker. METHODS: Forty-five patients with meningioma, 11 of whom underwent
      meningioma resection, as well as 30 healthy controls were enrolled in this study.
      CSF and blood samples were collected preoperatively and postoperatively.
      Expression levels of EFEMP1 were measured by enzyme-linked immunosorbent assay
      (ELISA). Receiver operating characteristic (ROC) curves were used to evaluate its
      discriminant ability. RESULTS: CSF EFEMP1 levels were significantly higher in the
      CSF samples (p < 0.0001) and serum samples (p = 0.0056) of meningioma patients
      compared to controls. To distinguish meningioma patients from controls by CSF and
      serum EFEMP1 levels, ROC/AUC analysis indicated an AUC of 0.945 (sensitivity
      0.933; specificity 0.833) and an AUC of 0.674 (sensitivity 0.867; specificity
      0.400), respectively. Moreover, the postoperative CSF levels of EFEMP1 were
      significantly decreased compared to the preoperative levels (p < 0.0001).
      CONCLUSIONS: The present study suggested that elevated EFEMP1 levels might be a
      novel diagnostic biomarker for meningioma patients.

PMID- 29035462
TI  - CpG-ODN Stimulation in Population Screening Monoclonal B-Cell Lymphocytosis.
AB  - BACKGROUND: Synthetic CpG-oligodeoxynucleotides (CpG-ODN) induce proliferation in
      normal and malignant lymphocytes B (LyB). This effect is widely exploited in CLL
      conventional chromosome banding analysis (CBA), which has become reliable only
      after the cultivation of CLL LyB using CpG-ODN stimulation in combination with IL
      2. Monoclonal B-cell lymphocytosis (MBL) differs from CLL mainly in clone size.
      Only cytogenetic data on recurrent chromosomal aberrations analyzed by
      fluorescence in situ hybridization (FISH) are available for population screening
      MBL (sMBL). In sMBL the clone of malignant LyB is typically below 10/uL. We
      compared CpGODN stimulation in healthy donors and in individuals with sMBL.
      METHODS: LyB and MBL LyB count were determined by flow cytometry in 15 samples
      from healthy subjects and 12 MBL cases. Mitotic indices were determined and CBA
      was done after cultivation of samples by CpG-ODN + IL2. In MBL samples, FISH
      analysis was performed on isolated LyB. RESULTS: MBL LyB clones in sMBL cases
      presented less than 1% of WBC and up to 33% of LyB. The MBL group was therefore
      compared to the group of healthy donors. Although normal and MBL group did not
      differ in WBC, overall LyB, and normal LyB count, a significantly higher mitotic
      index was observed in MBL samples (p = 0.0139). We were able to accomplish CBA in
      all samples which revealed a normal karyotype in all but one case. In this
      particular sMBL case FISH performed on isolated LyB showed 5% trisomy 12 which
      was later confirmed by CBA on CpG stimulated blood sample in 15% of metaphases.
      CONCLUSIONS: Our study, which was done on MBL cases obtained by population
      screening, confirmed that CpGODN preferentially induced proliferation in MBL LyB
      over normal LyB. Therefore, CBA can also be successfully accomplished in sMBL and
      can be used to additionally confirm clonality as well as to improve sensitivity
      of FISH analysis. Due to coexistence of comparable size of normal and malignant
      LyB, MBL can serve as a model for exvivo studying of LyB stimulation by CpG-ODN.

PMID- 29035463
TI  - Effect of Balanced Crystalloid, Gelatin and Hydroxyethyl Starch on Coagulation
      Detected by Rotational Thromboelastometry In Vitro.
AB  - BACKGROUND: Fluid resuscitation with crystalloid and colloid solutions is a
      common treatment in perioperative medicine. However, a variety of unbalanced or
      balanced solutions are used in clinical practice and there is still vivid debate
      going on regarding selection of optimal fluid with minimal negative effect on
      coagulation to minimize bleeding and blood transfusion requirements. The aim of
      the study was to investigate adverse effects of balanced crystalloids and
      colloids on coagulation measured by thromboelastometry in vitro. METHODS: Blood
      samples were obtained from healthy volunteers undergoing knee arthroscopy.
      Adverse effects of balanced crystalloid, hydroxyethyl starch, and gelatin were
      evaluated by thromboelastometry after 20% dilution of blood with the solution in
      vitro. Parameters of EXTEM and FIBTEM test were evaluated. RESULTS: Clotting time
      of EXTEM was not significantly influenced by any of the investigated solutions (p
      > 0.05). However, significant impairment of clot formation time of EXTEM was
      detected in hydroxyethyl starch and gelatin groups in comparison with controls (p
      < 0.05), while crystalloid did not affect this parameter significantly (p >
      0.05). Similar results were found in alpha angle although significant
      coagulopathy effect was found only in hydroxyethyl starch samples (p < 0.05).
      Maximum clot firmness of EXTEM and FIBTEM tests was significantly affected by
      both hydroxyethyl starch and gelatin (p < 0.05) but not by crystalloid.
      CONCLUSIONS: Balanced crystalloid solution does not seem to have a negative
      influence on the coagulation process as measured by thromboelastometry. On the
      other hand, balanced colloids may impair propagation phase of coagulation,
      strength of coagulum, and level of functional fibrinogen. Hydroxyethyl starch
      seems to have a stronger anticoagulant effect compared to gelatin.

PMID- 29035464
TI  - Galectin-3 Reflects Left Atrial Function being Assessed by Cardiac Magnetic
      Resonance Imaging.
AB  - BACKGROUND: This study aims to evaluate the association between galectin-3 and
      left atrial function (LAF) in patients undergoing cMRI. METHODS: Patients
      undergoing cMRI were prospectively enrolled. Right ventricular dysfunction (<
      50%) was excluded. Blood samples for biomarker measurements of galectin-3 and NT
      proBNP were collected at the time of cMRI examination. RESULTS: A total of 84
      patients were included. Median LVEF was 59% (IQR 51 - 64%). Galectin-3 was
      inversely correlated with overall LAF within a multivariable linear regression
      model (Beta -0.27; T -2.54; p = 0.01). Galectin-3 increased significantly
      according to the different stages of impaired LAF (p = 0.003) and was able to
      discriminate both patients with impaired LAF < 55% (AUC = 0.70, p = 0.002) and
      LAF < 45% (AUC = 0.69, p = 0.004). In multivariable logistic regression models,
      galectin-3 was still associated with impaired LAF (LAF < 55%: OR = 2.64, p =
      0.07; LAF < 45%: OR = 6.65, p = 0.007). CONCLUSIONS: This study demonstrates that
      galectin-3 is able to reflect LAF being assessed by cMRI.

PMID- 29035466
TI  - Friends in High Places.

PMID- 29035465
TI  - Enhanced Specificity of BRAF V600E Genotyping Using Wild-Type Blocker Coupled
      with Internal Competitive Reference in a Single Tube.
AB  - BACKGROUND: Mutations in the BRAF gene have been strongly associated with failure
      in cancer treatment using epidermal growth factor receptor (EGFR) antibodies. To
      better diagnose and assess the prognosis of cancer patients, mutation screening
      of the BRAFV600E gene should be performed prior to clinical anti-tumor drug
      therapy to avoid ineffective treatment. METHODS: In our previous study, we
      developed a real-time wild-type blocking PCR (WTB-PCR), which can amplify the
      mutant allele at high efficiency while simultaneously inhibiting the
      amplification of wild-type alleles. In order to reduce base mismatch due to the
      high number of cycles, as well as to monitor the total quantity of DNA added to
      the reaction system, an internal reference gene was co-amplified together with
      the target gene on the basis of WTB-PCR. RESULTS: Our results showed that when 50
      - 200 ng of the DNA templates was used, this current built method (realtime
      quantitative clamp-based PCR technology using wild-type blocker coupled with
      internal competitive reference to enhance amplification specificities, named
      wirePCR) completely blocked the amplification of the wild-type BRAFV600E gene
      with detection of the mutated allele at a mutant/wild-type ratio of 1:10,000,
      which was in line with the sensitivity requirement for the detection of trace
      amounts of the mutant gene. In the colorectal biopsies from 50 patients with
      suspected colorectal cancer, eight patients (16%) with BRAFV600E mutations were
      detected using wirePCR. The allele percentage of mutations can be obtained
      directly from the DeltaCq between the targeted and reference genes, we
      demonstrated that among the V600E-positive patient samples, the percentage of
      BRAF DNA with the V600E mutation ranged from 24.99% to 54.31%. CONCLUSIONS:
      WirePCR is a rapid, simple, and low-cost quantitative analytical technique for
      the detection of trace amounts of mutant BRAFV600E genes in clinical samples.

PMID- 29035467
TI  - Patients With Two Prescription Drug Refills Likely to Become Long-Term Users

PMID- 29035468
TI  - Undiagnosed Sleep Apnea Costing Billions.

PMID- 29035469
TI  - Embryonic Mouth Formation Explained.

PMID- 29035470
TI  - Virtual Dental Home Model of Care Proven to Be Effective.

PMID- 29035471
TI  - Sugar in the Spotlight.

PMID- 29035472
TI  - The fate of some urologic innovations from the last century.

PMID- 29035473
TI  - Which is the best way to treat a stone on a flexible ureterorrenoscopy? |
      Opinion: Fragmentation.

PMID- 29035475
TI  - Editorial Comment: Laparoscopic pectopexy: initial experience of single center
      with a new technique for apical prolapse surgery.

PMID- 29035474
TI  - Which is the best way to treat a stone on a flexible ureterorrenoscopy? |
      Opinion: Dusting.

PMID- 29035476
TI  - The clinical trials on gamma globulin for polio: victims of marketing success

PMID- 29035477
TI  - Fructose and Nonalcoholic Fatty Liver Disease

PMID- 29035478
TI  - Understanding the Impact of Added Sugar Consumption on Risk for Type 2 Diabetes.
AB  - The association between dietary sugar and type 2 diabetes (T2D) islikely mediated
      by the unregulated hepatic metabolism of fructose, which promoteshepatic and
      whole-body insulin resistance. Experimental evidence from clinicalstudies that
      utilize sensitive methods to test the effects of added sugar on
      insulinsensitivity is required. Establishing a causal link between added sugar
      and insulinresistance will help to stimulate health policies that target the
      reduction of addedsugar consumption and T2D prevention.

PMID- 29035479
TI  - Advocating for Soda Taxes: How Oral Health Professionals Fit In.
AB  - Our recent analysis of how soda tax debates appear in the newsrevealed that oral
      health professionals seldom appear. By elevating their expert voices,oral health
      practitioners can contribute new and salient arguments for soda taxesto the
      public discourse and help advance public policy that improves oral
      healthoutcomes. We propose media advocacy strategies that oral health
      professionals canuse to increase their visibility in the news to make the case
      for soda taxes.

PMID- 29035481
TI  - Understanding the Role of the Better Business Bureau.

PMID- 29035482
TI  - Nitrous Oxide Safe Practices.

PMID- 29035483
TI  - Timely Referrals--Our Ethical Obligations to Our Colleagues.

PMID- 29035484
TI  - Tech Trends. ILIFE V5s Robot Vacuum Cleaner.

PMID- 29035485
TI  - Tech Trends. Truebill.

PMID- 29035493
TI  - Medical Devices; Immunology and Microbiology Devices; Classification of the
      Nucleic Acid-Based Device for the Amplification, Detection, and Identification of
      Microbial Pathogens Directly From Whole Blood Specimens. Final order.
AB  - The Food and Drug Administration (FDA or we) is classifying the nucleic acid
      based device for the amplification, detection, and identification of microbial
      pathogens directly from whole blood specimens into class II (special controls).
      The special controls that apply to the device type are identified in this order
      and will be part of the codified language for the nucleic acid-based device for
      the amplification, detection, and identification of microbial pathogens directly
      from whole blood specimens' classification. We are taking this action because we
      have determined that classifying the device into class II (special controls) will
      provide a reasonable assurance of safety and effectiveness of the device. We
      believe this action will also enhance patients' access to beneficial innovative
      devices, in part by reducing regulatory burdens.

PMID- 29035494
TI  - Medical Devices; Immunology and Microbiology Devices; Classification of the
      Automated Image Assessment System for Microbial Colonies on Solid Culture Media.
      Final order.
AB  - The Food and Drug Administration (FDA or we) is classifying the automated image
      assessment system for microbial colonies on solid culture media into class II
      (special controls). The special controls that apply to the device type are
      identified in this order and will be part of the codified language for the
      automated image assessment system for microbial colonies on solid culture media's
      classification. We are taking this action because we have determined that
      classifying the device into class II (special controls) will provide a reasonable
      assurance of safety and effectiveness of the device. We believe this action will
      also enhance patients' access to beneficial innovative devices, in part by
      reducing regulatory burdens.

PMID- 29035495
TI  - Medical Devices; Gastroenterology-Urology Devices; Classification of the Enzyme
      Packed Cartridge. Final order.
AB  - The Food and Drug Administration (FDA or we) is classifying the enzyme packed
      cartridge into class II (special controls). The special controls that apply to
      the device type are identified in this order and will be part of the codified
      language for the enzyme packed cartridge's classification. We are taking this
      action because we have determined that classifying the device into class II
      (special controls) will provide a reasonable assurance of safety and
      effectiveness of the device. We believe this action will also enhance patients'
      access to beneficial innovative devices, in part by reducing regulatory burdens.

PMID- 29035496
TI  - Schedules of Controlled Substances: Placement of AB-CHMINACA, ABPINACA and THJ
      2201 Into Schedule I. Final rule.
AB  - With the issuance of this final rule, the Drug Enforcement Administration places
      N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3
      carboxamide (AB-CHMINACA), N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H
      indazole-3-carboxamide (AB-PINACA), and [1-(5-fluoropentyl)-1H-indazol-3
      yl](naphthalen-1-yl)methanone (THJ-2201), including their salts, isomers, and
      salts of isomers whenever the existence of such salts, isomers, and salts of
      isomers is possible, into schedule I of the Controlled Substances Act. This
      scheduling action is pursuant to the Controlled Substances Act which requires
      that such actions be made on the record after opportunity for a hearing through
      formal rulemaking. This rule continues the imposition of the regulatory controls
      and administrative, civil, and criminal sanctions applicable to schedule I
      controlled substances on persons who handle (manufacture, distribute, import,
      export, engage in research, conduct instructional activities or chemical
      analysis, or possess), or propose to handle AB-CHMINACA, AB-PINACA and THJ-2201.

PMID- 29035498
TI  - Highly Stable Molybdenum Disulfide Protected Silicon Photocathodes for
      Photoelectrochemical Water Splitting.
AB  - Developing materials, interfaces, and devices with improved stability remains one
      of the key challenges in the field of photoelectrochemical water splitting. As a
      barrier to corrosion, molybdenum disulfide is a particularly attractive
      protection layer for photocathodes due to its inherent stability in acid, the low
      permeability of its basal planes, and the excellent hydrogen evolution reaction
      (HER) activity the MoS2 edge. Here, we demonstrate a stable silicon photocathode
      containing a protecting layer consisting of molybdenum disulfide, molybdenum
      silicide, and silicon oxide which operates continuously for two months. We make
      comparisons between this system and another molybdenum sulfide-silicon
      photocathode embodiment, taking both systems to catastrophic failure during
      photoelectrochemical stability measurements and exploring mechanisms of
      degradation. X-ray photoelectron spectroscopy and transmission electron
      microscopy provide key insights into the origins of stability.

PMID- 29035497
TI  - Conformational Dynamics of DNA Binding and Cas3 Recruitment by the CRISPR RNA
      Guided Cascade Complex.
AB  - Bacteria and archaea rely on CRISPR (clustered regularly interspaced short
      palindromic repeats) RNA-guided adaptive immune systems for sequence specific
      elimination of foreign nucleic acids. In Escherichia coli, short CRISPR-derived
      RNAs (crRNAs) assemble with Cas (CRISPR-associated) proteins into a 405
      kilodalton multisubunit surveillance complex called Cascade (CRISPR-associated
      complex for antiviral defense). Cascade binds foreign DNA complementary to the
      crRNA guide and recruits Cas3, a trans-acting nuclease-helicase required for
      target degradation. Structural models of Cascade have captured static snapshots
      of the complex in distinct conformational states, but conformational dynamics of
      the 11-subunit surveillance complex have not been measured. Here, we use hydrogen
      deuterium exchange coupled to mass spectrometry (HDX-MS) to map conformational
      dynamics of Cascade onto the three-dimensional structure. New insights from
      structural dynamics are used to make functional predictions about the mechanisms
      of the R-loop coordination and Cas3 recruitment. We test these predictions in
      vivo and in vitro. Collectively, we show how mapping conformational dynamics onto
      static 3D-structures adds an additional dimension to the functional understanding
      of this biological machine.

PMID- 29035499
TI  - Hierarchical Self-Assembly of Cyclodextrin and Dimethylamino-Substituted Arylene
      Ethynylene on N-doped Graphene for Synergistically Enhanced Electrochemical
      Sensing of Dihydroxybenzene Isomers.
AB  - An electrochemically active sensing nanomaterial (denoted as CD-MPEA-NG) has been
      successfully constructed by an hierarchical self-assembly of cyclodextrin (CD)
      and N,N-dimethyl-4-(phenylethynyl)aniline (MPEA) on N-doped graphene (NG) in a
      low-temperature hydrothermal process. The unique nanostructure of the high
      performance CD-MPEA-NG was confirmed by utilizing Fourier transform infrared
      spectra, an X-ray diffractometer, and differential pulse voltammetry (DPV), etc.
      In particular, the method of density functional theory with dispersion energy
      (DFT-D) of wB97XD/LanL2DZ was employed to optimize and describe the face-to-face
      packing structure of heterodimers of NG and MPEA. The CD-MPEA-NG sensor exhibits
      highly sensitive performance toward dihydroxybenzene isomers, without relying on
      expensive noble metal or a complicated preparation process. The experimental
      results demonstrate that given the synergistic effect of NG and MPEA as a coupled
      sensing platform, CD as a supramolecular cavity can significantly enhance the
      electrochemical response. The detection limits (S/N = 3) for catechol (CT),
      resorcinol (RS), and hydroquinone (HQ) are 0.008, 0.018, and 0.011 MUM by DPV,
      respectively. Besides, the CD-MPEA-NG sensor shows a superb anti-interference,
      reproducibility, and stability, and satisfactory recovery aimed at detecting
      isomers in Nanjing River water. The encouraging performance as well as simplified
      preparation approach strongly support the CD-MPEA-NG sensor is a fascinating
      electrode to develop as a seamless and sensitive electroanalytical technique.

PMID- 29035500
TI  - Reliable Multistate Data Storage with Low Power Consumption by Selective
      Oxidation of Pyramid-Structured Resistive Memory.
AB  - Multilevel data storage using resistive random access memory (RRAM) has attracted
      significant attention for addressing the challenges associated with the rapid
      advances in information technologies. However, it is still difficult to secure
      reliable multilevel resistive switching of RRAM due to the stochastic and
      multiple formation of conductive filaments (CFs). Herein, we demonstrate that a
      single CF, derived from selective oxidation by a structured Cu active electrode,
      can solve the reliability issue. High-quality pyramidal Cu electrodes with a
      sharp tip are prepared via the template-stripping method. Morphology-dependent
      surface energy facilitates the oxidation of Cu atoms at the tip rather than in
      other regions, and the tip-enhanced electric fields can accelerate the transport
      of the generated Cu ions. As a result, CF growth occurs mainly at the tip of the
      pyramidal electrode, which is confirmed by high-resolution electron microscopy
      and elemental analysis. The RRAM exhibits highly uniform and low forming voltages
      (the average forming voltage and its standard deviation for 20 pyramid-based
      RRAMs are 0.645 and 0.072 V, respectively). Moreover, all multilevel resistance
      states for the RRAMs are clearly distinguished and show narrow distributions
      within 1 order of magnitude, leading to reliable cell-to-cell performance for MLC
      operation.

PMID- 29035501
TI  - Trapping Behaviors of Photogenerated Electrons on the (110), (101), and (221)
      Facets of SnO2: Experimental and DFT Investigations.
AB  - Spatial separation of photogenerated charges between different crystal facets has
      been observed in some semiconductor photocatalysts; however, the charge
      separation mechanism is still ambiguous. As a characteristic parameter of crystal
      facet, surface energy may be a crucial factor to dictate the flow of
      photogenerated charges. In this work, the relationship between surface energy and
      the flow mode of photogenerated charges is investigated by using model
      photocatalysts, including lance-shaped SnO2 particles and dodecahedral SnO2
      particles. The former are enclosed by two kinds of crystal facets with a big gap
      in surface energy, while the latter are composed of two types of crystal facets
      with nearly equal surface energy. However, the experimental results exhibit that
      the photogenerated electrons flow to all exposed crystal facets randomly in both
      two kinds of SnO2 nanocrystals, which is opposite to what has been observed in
      extensively investigated semiconductor photocatalysts including TiO2, SrTiO3,
      BiVO4, BiOCl, and Cu2O. Our results disqualify surface energy as an appropriate
      descriptor of preferential charge flow. Furthermore, the experimental results are
      confirmed by trapping energies and work functions calculated with the first
      principles methods, which are proved to be more relevant parameters for
      describing the charge flow direction. Additionally, the trapping sites on each
      crystal facet are determined by charge analysis.

PMID- 29035502
TI  - Binding Mechanism of the Model Charged Dye Carboxyfluorescein to
      Hyaluronan/Polylysine Multilayers.
AB  - Biopolymer-based multilayers become more and more attractive due to the vast span
      of biological application they can be used for, e.g., implant coatings, cell
      culture supports, scaffolds. Multilayers have demonstrated superior capability to
      store enormous amounts of small charged molecules, such as drugs, and release
      them in a controlled manner; however, the binding mechanism for drug loading into
      the multilayers is still poorly understood. Here we focus on this mechanism using
      model hyaluronan/polylysine (HA/PLL) multilayers and a model charged dye,
      carboxyfluorescein (CF). We found that CF reaches a concentration of 13 mM in the
      multilayers that by far exceeds its solubility in water. The high loading is not
      related to the aggregation of CF in the multilayers. In the multilayers, CF
      molecules bind to free amino groups of PLL; however, intermolecular CF-CF
      interactions also play a role and (i) endow the binding with a cooperative nature
      and (ii) result in polyadsorption of CF molecules, as proven by fitting of the
      adsorption isotherm using the BET model. Analysis of CF mobility in the
      multilayers by fluorescence recovery after photobleaching has revealed that CF
      diffusion in the multilayers is likely a result of both jumping of CF molecules
      from one amino group to another and movement, together with a PLL chain being
      bound to it. We believe that this study may help in the design of tailor-made
      multilayers that act as advanced drug delivery platforms for a variety of
      bioapplications where high loading and controlled release are strongly desired.

PMID- 29035504
TI  - Chromophore-Catalyst Assembly for Water Oxidation Prepared by Atomic Layer
      Deposition.
AB  - Visible-light-driven water splitting was investigated in a dye sensitized
      photoelectrosynthesis cell (DSPEC) based on a photoanode with a phosphonic acid
      derivatized donor-pi-acceptor (D-pi-A) organic chromophore, 1, and the water
      oxidation catalyst [Ru(bda)(4-O(CH2)3P(O3H2)2-pyr)2], 2, (pyr = pyridine; bda =
      2,2'-bipyridine-6,6'-dicarboxylate). The photoanode was prepared by using a
      layering strategy beginning with the organic dye anchored to an FTO|core/shell
      electrode, atomic layer deposition (ALD) of a thin layer (<1 nm) of TiO2, and
      catalyst binding through phosphonate linkage to the TiO2 layer. Device
      performance was evaluated by photocurrent measurements for core/shell
      photoanodes, with either SnO2 or nanoITO core materials, in acetate-buffered,
      aqueous solutions at pH 4.6 or 5.7. The absolute magnitudes of photocurrent
      changes with the core material, TiO2 spacer layer thickness, or pH, observed
      photocurrents were 2.5-fold higher in the presence of catalyst. The results of
      transient absorption measurements and DFT calculations show that electron
      injection by the photoexcited organic dye is ultrafast promoted by electronic
      interactions enabled by orientation of the dye's molecular orbitals on the
      electrode surface. Rapid injection is followed by recombination with the oxidized
      dye which is 95% complete by 1.5 ns. Although chromophore decomposition limits
      the efficiency of the DSPEC devices toward O2 production, the flexibility of the
      strategy presented here offers a new approach to photoanode design.

PMID- 29035503
TI  - Comparison between Short and Long Echo Time Magnetic Resonance Spectroscopic
      Imaging at 3T and 7T for Evaluating Brain Metabolites in Patients with Glioma.
AB  - Three-dimensional proton magnetic resonance spectroscopic imaging (MRSI) is a
      powerful non-invasive tool for characterizing spatial variations in metabolic
      profiles for patients with glioma. Metabolic parameters obtained using this
      technique have been shown to predict treatment response, disease progression, and
      transformation to a more malignant phenotype. The availability of ultra-high
      field MR systems has the potential to improve the characterization of
      metabolites. The purpose of this study was to compare the metabolite profiles
      acquired with conventional long echo time (TE) MRSI at 3T with those obtained
      with short TE MRSI at 3T and 7T in patients with glioma. The data acquisition
      parameters were optimized separately for each echo time and field strength to
      obtain volumetric coverage within clinically feasible data acquisition times of 5
      10 min. While a higher field strength did provide better detection of metabolites
      with overlapping peaks, spatial coverage was reduced and the use of inversion
      recovery to reduce lipid precluded the detection of lipid in regions of necrosis.
      For serial evaluation of large, heterogeneous lesions, the use of 3T short TE
      MRSI may thus be preferred. Despite the limited number of metabolites that it is
      able to detect, the use of 3T long TE MRSI gives the best contrast in choline/N
      acetyl aspartate between normal appearing brain and tumor and also allows the
      separate detection of lactate and lipid. It may therefore be preferred for serial
      evaluation of patients with high-grade glioma and for detection of malignant
      transformation in patients with low-grade glioma.

PMID- 29035505
TI  - High Oxygen Reduction Reaction Performances of Cathode Materials Combining
      Polyoxometalates, Coordination Complexes, and Carboneous Supports.
AB  - A series of carbonaceous-supported precious-metal-free polyoxometalate (POM)
      based composites which can be easily synthesized on a large scale was shown to
      act as efficient cathode materials for the oxygen reduction reaction (ORR) in
      neutral or basic media via a four-electron mechanism with high durability.
      Moreover, exploiting the versatility of the considered system, its activity was
      optimized by the judicious choice of the 3d metals incorporated in the {(PW9)2M7}
      (M = Co, Ni) POM core, the POM counterions and the support (thermalized triazine
      based frameworks (TTFs), fluorine-doped TTF (TTF-F), reduced graphene oxide, or
      carbon Vulcan XC-72. In particular, for {(PW9)2Ni7}/{Cu(ethylenediamine)2}/TTF-F,
      the overpotential required to drive the ORR compared well with those of Pt/C.
      This outstanding ORR electrocatalytic activity is linked with two synergistic
      effects due to the binary combination of the Cu and Ni centers and the strong
      interaction between the POM molecules and the porous and highly conducting TTF-F
      framework. To our knowledge, {(PW9)2Ni7}/{Cu(ethylenediamine)2}/TTF-F represents
      the first example of POM-based noble-metal-free ORR electrocatalyst possessing
      both comparable ORR electrocatalytic activity and much higher stability than that
      of Pt/C in neutral medium.

PMID- 29035506
TI  - Development and Evaluation of a Water-Based Flame Retardant Spray Coating for
      Cotton Fabrics.
AB  - In this Research Article, we report on the development of water-based flame
      retardant coating based on phospho-nitrogen combination for cotton fabrics. A one
      step spray-on process was employed to coat the fabrics by taking advantage of the
      spontaneous reaction between para-phenylenediamine (PDA) and
      tetrakis(hydroxymethyl)phosphonium chloride (THPC) resulting in an instantaneous
      precipitation of poly[1,4-diaminophenylene-tris(dimethyl hydroxymethyl)phosphine]
      (PApP) on the fabric surface. The effectiveness of PApP in improving the flame
      retardant properties like ignition resistance and lateral flame spread were
      evaluated in accordance with ASTM D6413 and BS EN ISO 15025 flammability tests.
      Despite the early (thermal) decomposition onset for coated fabrics under both
      oxidative and pyrolytic conditions, remarkably, self-extinguishing behavior (<3
      s) without any lateral flame spread was observed. Possible reaction scheme was
      also proposed to correlate flame retardant mechanism of the coated fabrics with
      the observations. Additional analysis via pyrolysis combustion flow calorimetry
      and vertical flame testing before and after washing showed that flame retardant
      efficiency did decrease with washing, but the overall performance was still
      promising.

PMID- 29035507
TI  - Sequential Delivery of Doxorubicin and Zoledronic Acid to Breast Cancer Cells by
      CB[7]-Modified Iron Oxide Nanoparticles.
AB  - Drug-loaded magnetic nanoparticles were synthesized and used for the sequential
      delivery of the antiresorptive agent zoledronic acid (Zol) and the cytotoxic drug
      doxorubicin (Dox) to breast cancer cells (MCF-7). Zol was attached to bare iron
      oxide nanoparticles (IONPs) via phosphonate coordination to form Z-NPs. The
      unbound imidazole of Zol was then used to complex the organic macrocycle CB[7] to
      obtain CZ-NPs. Dox was complexed to the CZ-NPs to form the fully loaded particles
      (DCZ-NPs), which were stable in solution at 37  degrees C and physiological pH
      (7.4). Fluorescence spectroscopy established that Dox is released in solution
      from DCZ-NPs suddenly (i) when the particles are subjected to magnetically
      induced heating to 42  degrees C at low pH (5.0) and (ii) in the presence of
      glutathione (GSH). Mass spectrometry indicated that Zol is released slowly in
      solution at low pH after Dox release. Magnetic measurements with a magnetic
      reader revealed that DCZ-NPs are internalized preferentially by MCF-7 cells
      versus nonmalignant cells (HEK293). Zol and Dox acted synergistically when
      delivered by the particles. DCZ-NPs caused a decrease in the viability of MCF-7
      cells that was greater than the net decrease caused when the drugs were added to
      the cells individually at concentrations equivalent to those delivered by the
      particles. MCF-7 cells were treated with DCZ-NPs and subjected to an alternating
      magnetic field (AMF) which, with the nanoparticles present, raised the
      temperature of the cells and triggered the intracellular release of Dox, as
      indicated by fluorescence activated cell sorting (FACS). The cytotoxic effects of
      the DCZ-NPs on MCF-7 cells were enhanced 10-fold by AMF-induced heating. DCZ-NPs
      were also able to completely inhibit MCF-7 cell adhesion and invasion in vitro,
      indicating the potential of the particles to act as antimetastatic agents.
      Together these results demonstrate that DCZ-NPs warrant development as a system
      for combined chemo- and thermo-therapeutic treatment of cancer.

PMID- 29035508
TI  - Three-Dimensionally Hierarchical Ni/Ni3S2/S Cathode for Lithium-Sulfur Battery.
AB  - Lithium-sulfur (Li-S) batteries have attracted interest as a promising energy
      storage technology due to their overwhelming advantages such as high energy
      density and low cost. However, their commercial success is impeded by
      deterioration of sulfur utilization, significant capacity fade, and poor cycle
      life, which are principally originated from the severe shuttle effect in relation
      to the dissolution and migration of lithium polysulfides. Herein, we proposed an
      effective and facile strategy to anchor the polysulfides and improve sulfur
      loading by constructing a three-dimensionally hierarchical Ni/Ni3S2/S cathode.
      This self-supported hybrid architecture is sequentially fabricated by the partial
      sulfurization of Ni foam by a mild hydrothermal process, followed by physical
      loading of elemental sulfur. The incorporation of Ni3S2, with high electronic
      conductivity and strong polysulfide adsorption capability, can not only empower
      the cathode to alleviate the shuttle effect, but also afford a favorable
      electrochemical environment with lower interfacial resistance, which could
      facilitate the redox kinetics of the anchored polysulfides. Consequently, the
      obtained Ni/Ni3S2/S cathode with a sulfur loading of ~4.0 mg/cm2 demonstrated
      excellent electrochemical characteristics. For example, at high current density
      of 4 mA/cm2, this thick cathode demonstrated a discharge capacity of 441 mAh/g at
      the 150th cycle.

PMID- 29035509
TI  - Positron Emission Tomography Assessment of the Intranasal Delivery Route for
      Orexin A.
AB  - Intranasal drug delivery is a noninvasive drug delivery route that can enhance
      systemic delivery of therapeutics with poor oral bioavailability by exploiting
      the rich microvasculature within the nasal cavity. The intranasal delivery route
      has also been targeted as a method for improved brain uptake of
      neurotherapeutics, with a goal of harnessing putative, direct nose-to-brain
      pathways. Studies in rodents, nonhuman primates, and humans have pointed to the
      efficacy of intranasally delivered neurotherapeutics, while radiolabeling studies
      have analyzed brain uptake following intranasal administration. In the present
      study, we employed carbon-11 radioactive methylation to assess the
      pharmacokinetic mechanism of intranasal delivery of Orexin A, a native
      neuropeptide and prospective antinarcoleptic drug that binds the orexin receptor
      1. Using physicochemical and pharmacological analysis, we identified the
      methylation sites and confirmed the structure and function of methylated Orexin A
      (CH3-Orexin A) prior to monitoring its brain uptake following intranasal
      administration in rodent and nonhuman primate. Through positron emission
      tomography (PET) imaging of [11C]CH3-Orexin A, we determined that the brain
      exposure to Orexin A is poor after intranasal administration. Additional ex vivo
      analysis of brain uptake using [125I]Orexin A indicated intranasal administration
      of Orexin A affords similar brain uptake when compared to intravenous
      administration across most brain regions, with possible increased brain uptake
      localized to the olfactory bulbs.

PMID- 29035511
TI  - Tuning the Multifunctionality of Iron Oxide Nanoparticles Using Self-Assembled
      Mixed Lipid Layers.
AB  - We present an approach to tuning the multifunctionality of iron oxide
      nanoparticles (IONs) using mixed self-assembled monolayers of cationic lipid and
      anionic polyethylene glycol (PEG) lipid. By forming stable, monodispersed lipid
      coated IONs (L-IONs) through a solvent-exchange technique, we were able to
      demonstrate the relationship between surface charge, the magnetic transverse
      relaxivity (r2 from T2-weighted images), and the binding capacity of small
      interfering ribonucleic acids (siRNAs) as a function of the cationic-to-anionic
      (PEG) lipid ratio. These properties were controlled by the cationic charge and
      the PEG conformation; relaxivity and siRNA binding could be varied in the
      mushroom and brush regimes but not at high brush densities. In vitro results
      combining cell viability, uptake, and transfection efficiency using HeLa cells
      suggest that the functional physicochemical and biological properties of L-IONs
      may be best achieved using catanionic lipid coatings near equimolar ratios of
      cationic to anionic PEG-lipids.

PMID- 29035512
TI  - Amperometric Detection of Sub-ppm Formaldehyde Using Single-Walled Carbon
      Nanotubes and Hydroxylamines: A Referenced Chemiresistive System.
AB  - We report amperometric detection of formaldehyde (HCHO) using hydroxylamine
      hydrochloride and single-walled carbon nanotubes (SWCNTs). Hydroxylamine
      hydrochloride reacts with HCHO to emit HCl vapor, which injects a hole carrier
      into semiconducting SWCNTs. The increase of conductivity in SWCNTs is easily
      monitored using an ohmmeter. The debundling of SWCNTs with a metallo
      supramolecular polymer (MSP) increased the active surface area in the SWCNTs
      network, leading to excellent sensitivity to HCHO with a limit of detection (LoD)
      of 0.016 ppm. The response of sensor is reversible, and the sensor is reusable.
      The selectivity to HCHO is 105-106 times higher than interferences with other
      volatiles such as water, methanol, and toluene. Moreover, false-positive
      responses caused by a significant variation of humidity and/or temperature are
      successfully discriminated from true-positive responses by using two sensors, one
      with and the other without hydroxylamine hydrochloride, in a referenced system.

PMID- 29035510
TI  - CRISPRi and CRISPRa Screens in Mammalian Cells for Precision Biology and
      Medicine.
AB  - Next-generation DNA sequencing technologies have led to a massive accumulation of
      genomic and transcriptomic data from patients and healthy individuals. The major
      challenge ahead is to understand the functional significance of the elements of
      the human genome and transcriptome, and implications for diagnosis and treatment.
      Genetic screens in mammalian cells are a powerful approach to systematically
      elucidating gene function in health and disease states. In particular, recently
      developed CRISPR/Cas9-based screening approaches have enormous potential to
      uncover mechanisms and therapeutic strategies for human diseases. The focus of
      this review is the use of CRISPR interference (CRISPRi) and CRISPR activation
      (CRISPRa) for genetic screens in mammalian cells. We introduce the underlying
      technology and present different types of CRISPRi/a screens, including those
      based on cell survival/proliferation, sensitivity to drugs or toxins, fluorescent
      reporters, and single-cell transcriptomes. Combinatorial screens, in which large
      numbers of gene pairs are targeted to construct genetic interaction maps, reveal
      pathway relationships and protein complexes. We compare and contrast CRISPRi and
      CRISPRa with alternative technologies, including RNA interference (RNAi) and
      CRISPR nuclease-based screens. Finally, we highlight challenges and opportunities
      ahead.

PMID- 29035513
TI  - When Heterotrimeric G Proteins Are Not Activated by G Protein-Coupled Receptors:
      Structural Insights and Evolutionary Conservation.
AB  - Heterotrimeric G proteins are signal-transducing switches conserved across
      eukaryotes. In humans, they work as critical mediators of intercellular
      communication in the context of virtually any physiological process. While G
      protein regulation by G protein-coupled receptors (GPCRs) is well-established and
      has received much attention, it has become recently evident that heterotrimeric G
      proteins can also be activated by cytoplasmic proteins. However, this alternative
      mechanism of G protein regulation remains far less studied than GPCR-mediated
      signaling. This Viewpoint focuses on recent advances in the characterization of a
      group of nonreceptor proteins that contain a sequence dubbed the "Galpha-binding
      and -activating (GBA) motif". So far, four proteins present in mammals [GIV (also
      known as Girdin), DAPLE, CALNUC, and NUCB2] and one protein in Caenorhabditis
      elegans (GBAS-1) have been described as possessing a functional GBA motif. The
      GBA motif confers guanine nucleotide exchange factor activity on Galphai subunits
      in vitro and activates G protein signaling in cells. The importance of this
      mechanism of signal transduction is highlighted by the fact that its
      dysregulation underlies human diseases, such as cancer, which has made the
      proteins attractive new candidates for therapeutic intervention. Here we discuss
      recent discoveries on the structural basis of GBA-mediated activation of G
      proteins and its evolutionary conservation and compare them with the better
      studied mechanism mediated by GPCRs.

PMID- 29035514
TI  - Structure and Electronic Properties of Interface-Confined Oxide Nanostructures.
AB  - The controlled fabrication of nanostructures has often used a substrate template
      to mediate and control the growth kinetics. Electronic substrate-mediated
      interactions have been demonstrated to guide the assembly of organic molecules or
      the nucleation of metal atoms but usually at cryogenic temperatures, where the
      diffusion has been limited. Combining STM, STS, and DFT studies, we report that
      the strong electronic interaction between transition metals and oxides could
      indeed govern the growth of low-dimensional oxide nanostructures. As a
      demonstration, a series of FeO triangles, which are of the same structure and
      electronic properties but with different sizes (side length >3 nm), are
      synthesized on Pt(111). The strong interfacial interaction confines the growth of
      FeO nanostructures, leading to a discrete size distribution and a uniform step
      structure. Given the same interfacial configuration, as-grown FeO nanostructures
      not only expose identical edge/surface structure but also exhibit the same
      electronic properties, as manifested by the local density of states and local
      work functions. We expect the interfacial confinement effect can be generally
      applied to control the growth of oxide nanostructures on transition metal
      surfaces. These oxide nanostructures of the same structure and electronic
      properties are excellent models for studies of nanoscale effects and
      applications.

PMID- 29035515
TI  - Isoform-Specific Substrate Inhibition Mechanism of Human Tryptophan Hydroxylase.
AB  - Tryptophan hydroxylase (TPH) catalyzes the initial and rate-limiting step in the
      biosynthesis of serotonin, which is associated with a variety of disorders such
      as depression and irritable bowel syndrome. TPH exists in two isoforms: TPH1 and
      TPH2. TPH1 catalyzes the initial step in the synthesis of serotonin in the
      peripheral tissues, while TPH2 catalyzes this step in the brain. In this study,
      the steady-state kinetic mechanism for the catalytic domain of human TPH1 has
      been determined. Varying substrate tryptophan (Trp) and tetrahydrobiopterin (BH4)
      results in a hybrid Ping Pong-ordered mechanism in which the reaction can either
      occur through a Ping Pong or a sequential mechanism depending on the
      concentration of tryptophan. The catalytic domain of TPH1 shares a sequence
      identity of 81% with TPH2. Despite the high sequence identity, differences in the
      kinetic parameters of the isoforms have been identified; i.e., only TPH1 displays
      substrate tryptophan inhibition. This study demonstrates that the difference can
      be traced to an active site loop which displays different properties in the TPH
      isoforms. Steady-state kinetic results of the isoforms, and variants with point
      mutations in a loop lining the active site, show that the kinetic parameters of
      only TPH1 are significantly changed upon mutations. Mutations in the active site
      loop of TPH1 result in an increase in the substrate inhibition constant, Ki, and
      therefore turnover rate. Molecular dynamics simulations reveal that this
      substrate inhibition mechanism occurs through a closure of the cosubstrate, BH4,
      binding pocket, which is induced by Trp binding.

PMID- 29035516
TI  - Potential Metabolic Activation of Representative Alkylated Polycyclic Aromatic
      Hydrocarbons 1-Methylphenanthrene and 9-Ethylphenanthrene Associated with the
      Deepwater Horizon Oil Spill in Human Hepatoma (HepG2) Cells.
AB  - Exposure to petrogenic polycyclic aromatic hydrocarbons (PPAHs) is the major
      human health hazard associated with the Deepwater Horizon oil spill. Alkylated
      phenanthrenes are the most abundant PPAHs present in the crude oil and could
      contaminate the food chain. We describe the metabolism of a C1-phenanthrene
      regioisomer 1-methylphenanthrene (1-MP) and a C2-phenanthrene regioisomer 9
      ethylphenanthrene (9-EP) in human HepG2 cells. The structures of the metabolites
      were identified by HPLC-UV-fluorescence detection and LC-MS/MS. Side chain
      hydroxylation of 1-MP and 9-EP was observed as the major metabolic pathway. The
      formation of 1-(hydroxymethyl)-phenanthrene was confirmed by reference to an
      authentic synthetic standard. However, formation of the bioactivated sulfate was
      not detected. Tetraols were also identified as signature metabolites of 1-MP and
      9-EP, indicating that metabolic activation occurred via the diol-epoxide pathway.
      O-Monosulfonated-catechols were discovered as signature metabolites of the o
      quinone pathway of metabolic activation of 1-MP and 9-EP, respectively. The
      identification of O-monosulfonated-catechols supports the metabolic activation of
      1-MP and 9-EP by P450 and AKR isozymes followed by metabolic detoxification of
      the o-quinone through interception of redox cycling by phase II isozymes. The
      signature metabolites identified could be used as biomarkers of human exposure to
      1-MP and 9-EP resulting from oil spills.

PMID- 29035517
TI  - Response to Comment on "Resource Footprints are Good Proxies of Environmental
      Damage".

PMID- 29035518
TI  - Manipulation and Assessment of Charge and Spin Delocalization in Mixed-Valent
      Triarylamine-Vinylruthenium Conjugates.
AB  - Triarylamine-vinylruthenium conjugates (4-RC6H4)2N{C6H4-4-CH?CHRu(CO)Cl(PiPr3)2},
      with R = CHO (1-CHO), C(?O)Me (1-Ac), COOMe (1-E), and Me (1-Me), have been
      prepared and investigated in their neutral, mono- and dioxidized states by cyclic
      voltammetry, IR, and UV/vis/near-infrared spectroelectrochemistry, electron
      paramagnetic resonance spectroscopy, and quantum-chemical calculations. Electron
      withdrawing substituents at the triarylamine moiety shift the charge and spin
      density toward the more electron-rich vinylruthenium site in comparison to the 4
      OMe-substituted triarylamine-vinylruthenium conjugate 1-OMe. A more asymmetric
      charge distribution changes the intense vibrationally structured intervalence
      charge-transfer (IVCT) band of completely delocalized, mixed-valent (MV) 1-OMe+
      to a weaker, highly asymmetric, nonsolvatochromic band with significantly smaller
      bandwidth at the low-energy side. The temperature dependence of the IVCT band of
      the formyl derivative 1-CHO+ proves that vibrational coupling of the IVCT
      transition to a symmetrical vibration is the underlying reason for band skewing.
      All of our results indicate that the MV radical cations remain electronically
      strongly coupled despite an increasingly stronger bias of the highest occupied
      molecular orbital to the vinylruthenium entity. Moreover, the dications of these
      complexes were found to be paramagnetic, which makes them rare examples of
      compounds that combine strong electronic coupling in the cationic MV state with
      paramagnetism of the dications.

PMID- 29035519
TI  - Hydrothermally Activated Graphene Fiber Fabrics for Textile Electrodes of
      Supercapacitors.
AB  - Carbon textiles are promising electrode materials for wearable energy storage
      devices owing to their conductive, flexible, and lightweight features. However,
      there still lacks a perfect choice for high-performance carbon textile electrodes
      with sufficient electrochemical activity. Graphene fiber fabrics (GFFs) are newly
      discovered carbon textiles, exhibiting various attractive properties, especially
      a large variability on the microstructure. Here we report the fabrication of
      hierarchical GFFs with significantly enlarged specific surface area using a
      hydrothermal activation strategy. By carefully optimize the activation process,
      the hydrothermally activated graphene fiber fabrics (HAGFFs) could achieve an
      areal capacitance of 1060 mF cm-2 in a very thin thickness (150 MUm) and the
      capacitance is easily magnified by overlaying several layers of HAGFFs, even up
      to a record value of 7398 mF cm-2. Meanwhile, a good rate capability and a long
      cycle life are also attained. As compared with other carbon textiles, including
      the commercial carbon fiber cloths, our HAGFFs present much better capacitive
      performance. Therefore, the mechanically stable, flexible, conductive, and highly
      active HAGFFs have provided an option for high-performance textile electrodes.

PMID- 29035520
TI  - Modeling Remineralization of Desalinated Water by Micronized Calcite Dissolution.
AB  - A widely used process for remineralization of desalinated water consists of
      dissolution of calcite particles by flow of acidified desalinated water through a
      bed packed with millimeter-size calcite particles. An alternative process
      consists of calcite dissolution by slurry flow of micron-size calcite particles
      with acidified desalinated water. The objective of this investigation is to
      provide theoretical models enabling design of remineralization by calcite slurry
      dissolution with carbonic and sulfuric acids. Extensive experimental results are
      presented displaying the effects of acid concentration, slurry feed
      concentration, and dissolution contact time. The experimental data are shown to
      be in agreement within less than 10% with theoretical predictions based on the
      simplifying assumption that the slurry consists of uniform particles represented
      by the surface mean diameter of the powder. Agreement between theory and
      experiment is improved by 1-8% by taking into account the powder size
      distribution. Apart from the practical value of this work in providing a hitherto
      lacking design tool for a novel technology. The paper has the merit of being
      among the very few publications providing experimental confirmation to the theory
      describing reaction kinetics in a segregated flow system.

PMID- 29035521
TI  - Direct Assembly of Magnetic Janus Particles at a Droplet Interface.
AB  - Self-assembly of nanoparticles at fluid-fluid interfaces is a promising route to
      fabricate functional materials from the bottom-up. However, directing and
      controlling particles into highly tunable and predictable structures, while
      essential, is a challenge. We present a liquid interface assisted approach to
      fabricate nanoparticle structures with tunable properties. To demonstrate its
      feasibility, we study magnetic Janus particles adsorbed at the interface of a
      spherical droplet placed on a substrate. With an external magnetic field turned
      on, a single particle moves to the location where its position vector relative to
      the droplet center is parallel to the direction of the applied field. Multiple
      magnetic Janus particles arrange into reconfigurable hexagonal lattice structures
      and can be directed to assemble at desirable locations on the droplet interface
      by simply varying the magnetic field direction. We develop an interface energy
      model to explain our observations, finding excellent agreement. Finally, we
      demonstrate that the external magnetic field allows one to tune the particle
      deposition pattern obtained when the droplet evaporates. Our results have
      implications for the fabrication of varied nanostructures on substrates for use
      in nanodevices, organic electronics, or advanced display, printing, and coating
      applications.

PMID- 29035522
TI  - Cobalt Ion Promoted Redox Cascade: A Route to Spiro Oxazine-Oxazepine Derivatives
      and a Dinuclear Cobalt(III) Complex of an N-(1,4-Naphthoquinone)-o-aminophenol
      Derivative.
AB  - The study discloses that the redox activity of N-(1,4-naphthoquinone)-o
      aminophenol derivatives (LRH2) containing a (phenol)-NH-(1,4-naphthoquinone)
      fragment is notably different from that of a (phenol)-NH-(phenol) precursor. The
      former is a platform for a redox cascade. LRH2 is redox noninnocent and exists in
      Cat-N-(1,4-naphthoquinone)(2-) (LR 2-) and SQ-N-(1,4-naphthoquinone) (LR *-)
      states in the complexes. Reactions of LRH2 with cobalt(II) salts in MeOH in air
      promote a cascade affording spiro oxazine-oxazepine derivatives (OXLR) in good
      yields, when R = H, Me, tBu. Spiro oxazine-oxazepine derivatives are bioactive,
      and such a molecule has so far not been isolated by a schematic route. In this
      context this cascade is significant. Dimerization of LRH2 -> OXLR in MeOH is a
      (6H+ + 6e) oxidation reaction and is composed of formations of four covalent
      bonds and 6-exo-trig and 7-endo-trig cyclization based on C-O coupling reactions,
      where MeOH is the source of a proton and the ester function. It was established
      that the active cascade precursor is [(LMe *-)CoIIICl2] (A). Notably, formation
      of a spiro derivative was not detected in CH3CN and the reaction ends up
      furnishing A. The route of the reaction is tunable by R, when R = NO2, it is a
      (2e + 4H+) oxidation reaction affording a dinuclear LR 2- complex of cobalt(III)
      of the type [(LNO2 2-)2CoIII2(OMe)2(H2O)2] (1) in good yields. No cascade occurs
      with zinc(II) ion even in MeOH and produces a LMe *- complex of type [(LMe *
      )ZnIICl2] (2). The intermediate A and 2 exhibit strong EPR signals at g = 2.008
      and 1.999, confrming the existence of LMe *- coordinated to low-spin cobalt(III)
      and zinc(II) ions. The intermediates of LRH2 -> OXLR conversion were analyzed by
      ESI mass spectrometry. The molecular geometries of OXLR and 1 were confirmed by X
      ray crystallography, and the spectral features were elucidated by TD DFT
      calculations.

PMID- 29035523
TI  - Current Stormwater Harvesting Guidelines Are Inadequate for Mitigating Risk from
      Campylobacter During Nonpotable Reuse Activities.
AB  - Campylobacter is a pathogen frequently detected in urban stormwater worldwide. It
      is one of the leading causes of enteric disease in many developed countries and
      is the leading cause of enteric disease in Australia. Prior to harvesting
      stormwater, adequate treatment is necessary to mitigate risks derived from such
      harmful pathogens. The goal of this research was to estimate the health risks
      associated with the exposure to Campylobacter when harvesting urban stormwater
      for toilet flushing and irrigation activities, and the role treatment options
      play in limiting risks. Campylobacter data collected from several urban
      stormwater systems in Victoria, Australia, were the inputs of a Quantitative
      Microbial Risk Assessment model. The model included seven treatment scenarios,
      spanning wetlands, biofilters, and more traditional treatment trains including
      those recommended by the Australian Guidelines for Water Recycling. According to
      our modeling and acceptable risk thresholds, only two treatment scenarios could
      supply water of sufficient quality for toilet flushing and irrigation end-uses:
      (1) using stormwater biofilters coupled with UV-treatment and (2) a more
      conventional coagulation, filtration, UV, and chlorination treatment plant.
      Importantly, our modeling results suggest that current guidelines in place for
      stormwater reuse are not adequate for protecting against exposure to
      Campylobacter. However, more research is required to better define whether the
      Campylobacter detectable in stormwater are pathogenic to humans.

PMID- 29035524
TI  - Reversible Iodine Capture by Nonporous Pillar[6]arene Crystals.
AB  - Here we report that easily obtained per-ethylated pillar[6]arene (EtP6) is a new
      adsorbent for iodine capture with high chemical and thermal stability. Nonporous
      EtP6 solids are shown to capture not only volatile iodine in the air but also
      iodine dissolved in an organic solvent and aqueous solution. Uptake of iodine
      leads to a structural transformation of EtP6 in the solid state. In the single
      crystal structure of iodine-doped EtP6 (I2@EtP6), each adsorbed iodine molecule
      is located between two adjacent EtP6 molecules to form a linear supramolecular
      polymer. Iodine is released spontaneously from I2@EtP6 solids when they are
      immersed in cyclohexane. These EtP6 solids can be reused many times without
      losing iodine capture capacity.

PMID- 29035525
TI  - Sesquiterpenes from the Endophyte Glomerella cingulata.
AB  - From the cultured endophytic fungus Glomerella cingulata isolated from a toxic
      plant, Gelsemium elegans, one new phenanthrene (1), four new sesquiterpenes (2
      5), and three known sesquiterpenes (6-8) were isolated. Their structures were
      elucidated using spectroscopic methods. Based on the ECD calculations, the
      absolute configurations of the new compounds were determined. Compounds 2, 4, and
      5 inhibited lipopolysaccharide (LPS)-induced NO production in BV2 cells by 50.6,
      36.1, and 29.4%, respectively, at 1 MUM (positive control curcumin, IC50 = 4.0
      MUM).

PMID- 29035526
TI  - Interplay among Sequence, Folding Propensity, and Bio-Piezoelectric Response in
      Short Peptides and Peptoids.
AB  - Many biomaterials are piezoelectric (i.e., mechanically deform under an applied
      electric field); however, the molecular origin of this phenomenon remains
      unclear. In the case of protein-based scaffolds, one possibility involves
      flexible response of local folding motifs to the applied field. Here, we test
      this hypothesis by examining the piezoresponse in a series of helical peptide
      based oligomers. Control over folding propensity is exerted through systematic
      variation in both side-chain sequence and backbone composition. Piezoresponse is
      quantified by piezo-force microscopy on polar self-assembled monolayers. The
      results indicate backbone rigidity is an important determinant in peptide
      electromechanical responsiveness.

PMID- 29035527
TI  - Carbon-Carbon Bonding between Nitrogen Heterocyclic Carbenes and CO2.
AB  - Ab initio MP2/aug'-cc-pVTZ calculations were performed to identify equilibrium
      complexes and molecules and the transition structures that interconvert them, on
      the potential energy surfaces of a series of seven binary systems that have
      nitrogen heterocyclic carbenes (NHCs) as the electron-pair donors to CO2. Seven
      of the NHCs form complexes stabilized by C...C tetrel bonds, and six of these
      seven are also stabilized by a secondary interaction between an O of CO2 and the
      adjacent N-H group of the carbene. Six of the seven NHCs also form stable
      molecules with C-C covalent bonds, and with one exception, these molecules have
      binding energies that are significantly greater than the binding energies of the
      complexes. Charge-transfer stabilizes all of the NHC:CO2 complexes and occurs
      from the C lone pair of the carbene to the CO2 molecule. The six complexes that
      have secondary stabilizing interactions are also stabilized by back-donation of
      charge from the O to the adjacent N-H group of the carbene. Transition structures
      present barriers to the interconversion of complexes and molecules. With one
      exception, the barrier for converting a molecule to a complex is much greater
      than the barrier for the reverse reaction. Atoms in Molecules bonding parameters,
      shifts of IR C-O stretching and O-C-O bending frequencies, changes in NMR 13C
      chemical shieldings, and changes in C-C and C-O coupling constants as 1tJ(C-C)
      and J(C-O) for complexes and transition structures become 1J(C-C) and 2J(C-O) for
      molecules, are all consistent with the changing nature of the C...C tetrel bond
      in the complex through the transition state to a covalent C-C bond in the
      molecule.

PMID- 29035528
TI  - Role of Flavonols and Proanthocyanidins in the Sensory Quality of Sea Buckthorn
      (Hippophae rhamnoides L.) Berries.
AB  - Sensory profile, flavonols, proanthocyanidins, sugars, and organic acids were
      investigated in purees of six sea buckthorn (Hippophae rhamnoides) cultivars. The
      sensory profiles of the purees were dominated by intense sourness followed by
      astringency and bitterness due to the high content of malic acid. Malic acid and
      isorhamnetin glycosides, especially isorhamnetin-3-O-sophoroside-7-O-rhamnoside,
      had close association with the astringent attributes in the different purees,
      whereas some of the known astringent compounds such as proanthocyanidin dimers
      and trimers or quercetin glycosides, had less impact. Moreover, the ratios
      between contents of acids and phenolic compounds were more important predictors
      of bitterness than the individual variables alone. Astringency and bitterness are
      important sensory factors for the consumer acceptance of sea buckthorn products.
      The current study provides new knowledge on the correlations between sensory
      properties and composition and supports industrial utilization of the sea
      buckthorn berries.

PMID- 29035529
TI  - MD and QM/MM Study of the Quaternary HutP Homohexamer Complex with mRNA, l
      Histidine Ligand, and Mg2.
AB  - The HutP protein from B. subtilis regulates histidine metabolism by interacting
      with an antiterminator mRNA hairpin in response to the binding of l-histidine and
      Mg2+. We studied the functional ligand-bound HutP hexamer complexed with two
      mRNAs using all-atom microsecond-scale explicit-solvent MD simulations performed
      with the Amber force fields. The experimentally observed protein-RNA interface
      exhibited good structural stability in the simulations with the exception of some
      fluctuations in an unusual adenine-threonine interaction involving two closely
      spaced H-bonds. We further investigated this interaction by comparing QM/MM and
      MM optimizations, using the QM region comprising almost 350 atoms described at
      the DFT-D3 level. The QM/MM method clearly improved the adenine-threonine
      interaction compared to MM, especially when the X-H bond lengths were frozen
      during the MM optimization to mimic the use of SHAKE in the MD simulations. Thus,
      both the MM approximation and the use of SHAKE can compromise the description of
      H-bonds at protein-RNA interfaces. The simulations also revealed a notable Mg2+
      parameter dependence in the behavior of the ligand-binding pocket (LBP). With the
      SPC/E water model, the 12-6 Aqvist and Li&Merz parameters provided an entirely
      stable LBP structure, but the 12-6 Allner and 12-6-4 Li&Merz parametrizations
      resulted in a progressive loss of direct nitrogen-Mg2+ LBP coordination. The
      Allner and Li&Merz 12-6 parametrizations were also tested with the TIP3P water
      model; the LBP was destabilized in both cases. This illustrates the difficulty of
      consistently describing different Mg2+ interactions using nonpolarizable force
      fields. Overall, the simulations support the hypothesis that HutP protein becomes
      fully structured upon ligand binding. Subsequent RNA binding does not affect the
      protein structure, in keeping with the mechanism inferred from experimental
      structures.

PMID- 29035530
TI  - Correction to Synthetic Approaches to the New Drugs Approved During 2015.

PMID- 29035531
TI  - Molecular Simulations of Melittin-Induced Membrane Pores.
AB  - Membrane-active peptides (MAPs) are able to induce pores in cell membranes via
      molecular mechanisms, which are still subject to ongoing research. In this work,
      we present molecular dynamics simulations that suggest a precursor membrane
      defect plays an important role in the pore-inducing activity of the prototypical
      antimicrobial peptide melittin. The simulations reveal that the hydrophobic N
      terminus of melittin is able to recognize and insert into the membrane defect in
      the lipid bilayer and that this leads to a cascading transfer of adsorbed
      peptides to the membrane defect, leading to peptide aggregation in the pore. We
      show that this mechanism also acts in the case of a melittin mutant without the
      flexible central proline hinge, thus indicating the latter is not crucial to the
      activity of melittin, which is consistent with experiments.

PMID- 29035532
TI  - Unusual Long-Range Ordering Incommensurate Structural Modulations in an Organic
      Molecular Ferroelectric.
AB  - The incommensurate (IC) behaviors of ferroelectrics have been widely investigated
      in inorganic oxides as an exciting branch for aperiodic materials, whereas it
      still remains a great challenge to achieve such intriguing effects in organic
      systems. Here, we present that successive ordering of dynamic dipoles in an
      organic molecular ferroelectric, N-isopropylbenzylaminium trichloroacetate (1),
      enables unusual incommensurately modulated structures between its paraelectric
      phase and ferroelectric phase. In particular, 1 exhibits three distinct IC states
      coupling with a long-range ordering modulation. That is, the incommensurately
      modulated lattice is ~7 times as large as its periodic prototype, and the IC
      structure is well solved using a (3 + 1)D superspace group with the modulated
      wavevector q = (0, 0, 0.1589). To the best of our knowledge, 1 is the first
      organic ferroelectric showing such a long-range ordering IC structural
      modulation. In addition, structural analyses reveal that slowing down dynamic
      motions of anionic moieties accounts for its modulation behaviors, which also
      results in dramatic reorientation of dipolar moments and concrete ferroelectric
      polarization of 1 (~0.65 MUC/cm2). The combination of unique IC structural
      modulations and ferroelectricity makes 1 a potential candidate for the assembly
      of an artificially modulated lattice, which will allow for a deep understanding
      of the underlying chemistry and physics of aperiodic materials.

PMID- 29035533
TI  - Bond-Selective Imaging of Cells by Mid-Infrared Photothermal Microscopy in High
      Wavenumber Region.
AB  - Using a visible beam to probe the thermal effect induced by infrared absorption,
      mid-infrared photothermal (MIP) microscopy allows bond-selective chemical imaging
      at submicron spatial resolution. Current MIP microscopes cannot reach the high
      wavenumber region due to the limited tunability of the existing quantum cascade
      laser source. We extend the spectral range of MIP microscopy by difference
      frequency generation (DFG) from two chirped femtosecond pulses. Flexible
      wavelength tuning in both C-D and C-H regions was achieved with mid-infrared
      power up to 22.1 mW and spectral width of 29.3 cm-1. Distribution of fatty acid
      in live human lung cancer cells was revealed by MIP imaging of the C-D bond at
      2192 cm-1.

PMID- 29035534
TI  - Rovibrational Characterization of High-Lying Electronic States of Cu2 by Double
      Resonant Nonlinear Spectroscopy.
AB  - The available knowledge of the electronically excited states of the copper dimer
      is limited. This is common for transition metals, as the high density of states
      hinders both experimental assignment and computation. In this work, two-color
      resonant four-wave mixing spectroscopy was applied to neutral Cu2 in the gas
      phase. The method yielded accurate positions of individual rovibrational lines in
      the I-X and J-X electronic systems. This revealed the term symbols for the I and
      J states as 1Piu (1u) and 1Sigmau+ (0u+), respectively. For the 63Cu2
      isotopologue, accurate molecular constants were obtained. The characterization of
      the J state finally allowed decisive determination of its electron configuration.
      The J state is obtained from the ground state by promotion of a 3dpig electron
      into the weakly bonding 4ppiu molecular orbital. From the data analysis,
      lifetimes of the I state (between 10 ps and 5 ns) and J state (66 ns) were
      inferred.

PMID- 29035535
TI  - Report and Application of a Tool Compound Data Set.
AB  - Small molecule tool compounds have enabled profound advances in life science
      research. These chemicals are potent, cell active, and selective, and, thus, are
      suitable for interrogating biological processes. For these chemicals to be useful
      they must be correctly characterized and researchers must be aware of them. We
      mined the ChEMBL bioactivity database to identify high quality tool compounds in
      an unbiased way. We identified 407 best-in-class compounds for 278 protein
      targets, and these are reported in an annotated data set. Additionally, we
      developed informatics functions and a web application for data visualization and
      automated pharmacological hypothesis generation. These functions were used to
      predict inhibitors of the Chromobox Protein Homologue 5 (CBX5) mediated gene
      repression pathway that currently lacks appropriate inhibitors. The predictions
      were subsequently validated by a highly specific cell based assay, revealing new
      chemical modulators of CBX5-mediated heterochromatin formation. This data set and
      associated functions will help researchers make the best use of these valuable
      compounds.

PMID- 29035537
TI  - Discovery of a Novel Piperidine-Based Inhibitor of Cholesteryl Ester Transfer
      Protein (CETP) That Retains Activity in Hypertriglyceridemic Plasma.
AB  - Herein we describe the discovery and characterization of a novel, piperidine
      based inhibitor of cholesteryl ester transfer protein (CETP) with a core
      structure distinct from other reported CETP inhibitors. A versatile synthesis
      starting from 4-methoxypyridine enabled an efficient exploration of the SAR,
      giving a lead molecule with potent CETP inhibition in human plasma. The
      subsequent optimization focused on improvement of pharmacokinetics and mitigation
      of off-target liabilities, such as CYP inhibition, whose improvement correlated
      with increased lipophilic efficiency. The effort led to the identification of an
      achiral, carboxylic acid-bearing compound 16 (TAP311) with excellent
      pharmacokinetics in rats and robust efficacy in hamsters. Compared to
      anacetrapib, the compound showed substantially reduced lipophilicity, had only
      modest distribution into adipose tissue, and retained potency in
      hypertriglyceridemic plasma in vitro and in vivo. Furthermore, in contrast to
      torcetrapib, the compound did not increase aldosterone secretion in human
      adrenocortical carcinoma cells nor in chronically cannulated rats. On the basis
      of its preclinical efficacy and safety profile, the compound was advanced into
      clinical trials.

PMID- 29035536
TI  - HDAC8 Substrates Identified by Genetically Encoded Active Site Photocrosslinking.
AB  - The histone deacetylase family comprises 18 enzymes that catalyze deacetylation
      of acetylated lysine residues; however, the specificity and substrate profile of
      each isozyme remains largely unknown. Due to transient enzyme-substrate
      interactions, conventional co-immunoprecipitation methods frequently fail to
      identify enzyme-specific substrates. Additionally, compensatory mechanisms often
      limit the ability of knockdown or chemical inhibition studies to achieve
      significant fold changes observed by acetylation proteomics methods. Furthermore,
      measured alterations do not guarantee a direct link between enzyme and substrate.
      Here we present a chemical crosslinking strategy that incorporates a
      photoreactive, non-natural amino acid, p-benzoyl-l-phenylalanine, into various
      positions of the structurally characterized isozyme histone deacetylase 8
      (HDAC8). After covalent capture, co-immunoprecipitation, and mass spectrometric
      analysis, we identified a subset of HDAC8 substrates from human cell lysates,
      which were further validated for catalytic turnover. Overall, this chemical
      crosslinking approach identified novel HDAC8-specific substrates with high
      catalytic efficiency, thus presenting a general strategy for unbiased deacetylase
      substrate discovery.

PMID- 29035538
TI  - Resolving the Spatial Structures of Bound Hole States in Black Phosphorus.
AB  - Understanding the local electronic properties of individual defects and dopants
      in black phosphorus (BP) is of great importance for both fundamental research and
      technological applications. Here, we employ low-temperature scanning tunnelling
      microscope (LT-STM) to probe the local electronic structures of single acceptors
      in BP. We demonstrate that the charge state of individual acceptors can be
      reversibly switched by controlling the tip-induced band bending. In addition,
      acceptor-related resonance features in the tunnelling spectra can be attributed
      to the formation of Rydberg-like bound hole states. The spatial mapping of the
      quantum bound states shows two distinct shapes evolving from an extended ellipse
      shape for the 1s ground state to a dumbbell shape for the 2px excited state. The
      wave functions of bound hole states can be well-described using the hydrogen-like
      model with anisotropic effective mass, corroborated by our theoretical
      calculations. Our findings not only provide new insight into the many-body
      interactions around single dopants in this anisotropic two-dimensional material
      but also pave the way to the design of novel quantum devices.

PMID- 29035539
TI  - Three-Fold-Symmetric Selenium-Donor Metallaboratranes of Cobalt and Nickel.
AB  - A novel selenium-containing pyridazinyl-based soft scorpionate ligand (KTnse) was
      synthesized. It reacts with CoCl2 and NiCl2, yielding the first metallaboratrane
      complexes with selenium in their donor positions. Further substitution with
      Ag(OTf) or NaN3 allows isolation of the respective triflate or azide complexes.
      Reaction with Ag(OTf) leads in the case of nickel to a dinuclear, dicationic
      complex with a short Ni-Ni distance, while cobalt gave a mononuclear cationic
      species. Substitution of the chloride by azide yields with both metals the
      respective azide complexes. All compounds were characterized via single-crystal X
      ray diffraction analysis. Density functional theory calculations on the chloride
      species point to oxidized cobalt(III) and nickel(III) centers.

PMID- 29035541
TI  - Hydration Phase Diagram of Clay Particles from Molecular Simulations.
AB  - Adsorption plays a fundamental role in the behavior of clays. Because of the
      confinement between solid clay layers on the nanoscale, adsorbed water is
      structured in layers, which can occupy a specific volume. The transition between
      these states is intimately related to key features of clay thermo-hydro
      mechanical behavior. In this article, we consider the hydration states of clays
      as phases and the transition between these states as phase changes. The
      thermodynamic formulation supporting this idea is presented. Then, the results
      from grand canonical Monte Carlo simulations of sodium montmorillonite are used
      to derive hydration phase diagrams. The stability analysis presented here
      explains the coexistence of different hydration states at clay particle scale and
      improves our understanding of the irreversibilities of clay thermo-hydro
      mechanical behavior. Our results provide insights into the mechanics of the
      elementary constituents of clays, which is crucial for a better understanding of
      the macroscopic behavior of clay-rich rocks and soils.

PMID- 29035540
TI  - Targetable Clinical Nanoparticles for Precision Cancer Therapy Based on Disease
      Specific Molecular Inflection Points.
AB  - Novel translational approaches based on clinical modular nanoplatforms are needed
      in order to treat solid cancers according to their discrete molecular features.
      In the present study, we show that the clinical nanopharmaceutical Ferumoxytol,
      which consists of a glucose-based coat surrounding an iron oxide core, could
      identify molecular characteristics of prostate cancer, corresponding to unique
      phases of the disease continuum. By affixing a targeting probe for the prostate
      specific membrane antigen on its surface, the nanopharmaceutical was able to
      assess the functional state of the androgen receptor pathway via MRI, guiding
      therapy and delivering it with the same clinical nanoparticle. In order to
      simultaneously inhibit signaling from key oncogenic pathways of more advanced
      forms of prostate cancer, a single-agent therapy for early stage disease to
      inhibit DNA replication, as well as combination therapy with two drugs co
      retained within the nanopharmaceutical's polymeric coating, were tested and
      resulted in complete tumor ablation. Recalcitrant and terminal forms of the
      disease were effectively treated with a nanopharmaceutical delivering a
      combination that upregulates endoplasmic reticulum stress and inhibits
      metastasis, thereby showing that this multifunctional nanoplatform can be used in
      the clinic for patient stratification, as well as precision treatment based on
      the individual's unique disease features.

PMID- 29035542
TI  - Linear Chain Formation of Split-Aptamer Dimers on Surfaces Triggered by
      Adenosine.
AB  - The detection of small molecules impacts various fields; however, their small
      size and low concentration are usually the cause of limitations in their
      detection. Thus, the need for biosensors with appropriate probes and signal
      amplification strategies is required. Aptamers are appropriate probes selected
      specifically against small targets such as adenosine. The possibility to split
      aptamers in parts led to original amplification strategies based on sandwich
      assays. By combining the self-assembling of oligonucleotide dimers with split
      aptamer dangling ends and a surface plasmon resonance imaging technique, we
      developed an original amplification approach based on linear chain formation in
      the presence of the adenosine target. In this article, on the basis of sequence
      engineering, we analyzed its performance and the effect of the probe grafting
      density on the length of the chains formed at the surface of the biosensor.

PMID- 29035543
TI  - Speciated Monitoring of Gas-Phase Organic Peroxy Radicals by Chemical Ionization
      Mass Spectrometry: Cross-Reactions between CH3O2, CH3(CO)O2, (CH3)3CO2, and c
      C6H11O2.
AB  - Organic peroxy radicals ("RO2", with R organic) are key intermediates in most
      oxygen-rich systems, where organic compounds are oxidized (natural environment,
      flames, combustion engines, living organisms, etc). But, until recently,
      techniques able to monitor simultaneously and distinguish between RO2 species
      ("speciated" detection) have been scarce, which has limited the understanding of
      complex systems containing these radicals. Mass spectrometry using proton
      transfer ionization has been shown previously to detect individual gas-phase RO2
      separately. In this work, we illustrate its ability to speciate and monitor
      several RO2 simultaneously by investigating reactions involving CH3O2, CH3C(O)O2,
      c-C6H11O2, and (CH3)3CO2. The detection sensitivity of each of these radicals was
      estimated by titration with NO to between 50 and 1000 Hz/ppb, with a factor from
      3 to 5 of uncertainties, mostly due to the uncertainties in knowing the amounts
      of added NO. With this, the RO2 concentration in the reactor was estimated
      between 1 * 1010 and 1 * 1012 molecules cm-3. When adding a second radical
      species to the reactor, the kinetics of the cross-reaction could be studied
      directly from the decay of the first radical. The time-evolution of two and
      sometimes three different RO2 was followed simultaneously, as the CH3O2 produced
      in further reaction steps was also detected in some systems. The rate
      coefficients obtained are (in molecule-1 cm3 s-1): kCH3O2+CH3C(O)O2 = 1.2 * 10
      11, kCH3O2+t-butylO2 = 3.0 * 10-15, kc-hexylO2+CH3O2 = 1.2 * 10-13, kt
      butylO2+CH3C(O)O2 = 3.7 * 10-14, and kc-hexylO2+t-butylO2 = 1.5 * 10-15. In spite
      of their good comparison with the literature and good reproducibility, large
      uncertainties (*5/5) are recommended on these results because of those in the
      detection sensitivities. This work is a first illustration of the potential
      applications of this technique for the investigation of organic radicals in
      laboratory and in more complex systems.

PMID- 29035544
TI  - Addressing the Fundamental Electronic Properties of Wurtzite GaAs Nanowires by
      High-Field Magneto-Photoluminescence Spectroscopy.
AB  - At ambient conditions, GaAs forms in the zincblende (ZB) phase with the notable
      exception of nanowires (NWs) where the wurtzite (WZ) lattice is also found. The
      WZ formation is both a complication to be dealt with and a potential feature to
      be exploited, for example, in NW homostructures wherein ZB and WZ phases
      alternate controllably and thus band gap engineering is achieved. Despite intense
      studies, some of the fundamental electronic properties of WZ GaAs NWs are not
      fully assessed yet. In this work, by using photoluminescence (PL) under high
      magnetic fields (B = 0-28 T), we measure the diamagnetic shift, DeltaEd, and the
      Zeeman splitting of the band gap free exciton in WZ GaAs formed in core-shell
      InGaAs-GaAs NWs. The quantitative analysis of DeltaEd at different temperatures
      (T = 4.2 and 77 K) and for different directions of B? allows the determination of
      the exciton reduced mass, MUexc, in planes perpendicular (MUexc = 0.052 m0, where
      m0 is the electron mass in vacuum) and parallel (MUexc = 0.057 m0) to the c axis
      of the WZ lattice. The value and anisotropy of the exciton reduced mass are
      compatible with the electron lowest-energy state having Gamma7C instead of
      Gamma8C symmetry. This finding answers a long discussed issue about the correct
      ordering of the conduction band states in WZ GaAs. As for the Zeeman splitting,
      it varies considerably with the field direction, resulting in an exciton
      gyromagnetic factor equal to 5.4 and ~0 for B?//c and B??c, respectively. This
      latter result provides fundamental insight into the band structure of wurtzite
      GaAs.

PMID- 29035546
TI  - GRadient Adaptive Decomposition (GRAD) Method: Optimized Refinement Along
      Macrostate Borders in Markov State Models.
AB  - Markov state models (MSM) are used to model the kinetics of processes sampled by
      molecular dynamics (MD) simulations. MSM reduce the high dimensionality inherent
      to MD simulations as they partition the free energy landscape into discrete
      states, generating a kinetic model as a series of uncorrelated jumps between
      states. Here, we detail a new method, called GRadient Adaptive Decomposition,
      which optimizes coarse-grained MSM by refining borders with respect to the
      gradient along the free energy surface. The proposed method requires only a small
      number of initial microstates because it corrects for errors produced by limited
      sampling. Whereas many methods rely on fuzzy partitions for proper statistics,
      GRAD retains a crisp decomposition. Two test studies are presented to illustrate
      the method and assess its accuracy: the first analyzes MSM of idealized model
      potentials, while the second is a study of the dynamics of unstacking of the
      deoxyribose adenosine monophosphate dinucleotide.

PMID- 29035545
TI  - Determination of n-Type Doping Level in Single GaAs Nanowires by
      Cathodoluminescence.
AB  - We present an effective method of determining the doping level in n-type III-V
      semiconductors at the nanoscale. Low-temperature and room-temperature
      cathodoluminescence (CL) measurements are carried out on single Si-doped GaAs
      nanowires. The spectral shift to higher energy (Burstein-Moss shift) and the
      broadening of luminescence spectra are signatures of increased electron
      densities. They are compared to the CL spectra of calibrated Si-doped GaAs
      layers, whose doping levels are determined by Hall measurements. We apply the
      generalized Planck's law to fit the whole spectra, taking into account the
      electron occupation in the conduction band, the bandgap narrowing, and band
      tails. The electron Fermi levels are used to determine the free electron
      concentrations, and we infer nanowire doping of 6 * 1017 to 1 * 1018 cm-3. These
      results show that cathodoluminescence provides a robust way to probe carrier
      concentrations in semiconductors with the possibility of mapping spatial
      inhomogeneities at the nanoscale.

PMID- 29035547
TI  - Pharmacokinetics and Pharmacodynamics of the Triterpenoid Ursolic Acid in
      Regulating the Antioxidant, Anti-inflammatory, and Epigenetic Gene Responses in
      Rat Leukocytes.
AB  - The triterpenoid ursolic acid (UA) has been proposed as a potential cancer
      chemopreventive agent in many preclinical and clinical studies. In the present
      work, we aimed to characterize the pharmacokinetics (PK) of UA and to
      quantitatively assess the antioxidative and anti-inflammatory effects of UA,
      which are potentially linked to its chemopreventive efficacy. UA was administered
      intravenously (i.v., 20 mg/kg) or by oral gavage (100 mg/kg) to male Sprague
      Dawley rats, and blood samples were collected at a series of designated time
      points. The plasma concentration of UA was determined using a validated liquid
      chromatography-mass spectrometry (LC-MS) approach. A biexponential decline in the
      UA plasma concentration was observed after i.v. dosing and was fitted to a two
      compartmental model. The expression levels of phase II drug metabolism
      (DM)/antioxidant genes and the inflammatory iNos gene in corresponding treatment
      arms were measured using qPCR as a pharmacodynamic (PD) marker. The expression of
      phase II DM/antioxidant genes increased and peaked approximately 3 h after 20
      mg/kg UA treatment. In a lipopolysaccharide (LPS)-induced acute inflammation
      model, UA inhibited LPS-stimulated iNos expression and that of the epigenetic
      markers the DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) in
      leukocytes. A PK-PD model using Jusko's indirect response model (IDR) with
      transition compartments (TC) was established to describe the time delay and
      magnitude of the gene expression elicited by UA. The PK-PD model provided
      reasonable fitting linking the plasma concentration of UA simultaneously with the
      PD response based on leukocyte mRNA expression. Overall, our results indicate
      that UA is effective at inducing various phase II DM/antioxidant genes and
      inhibiting pro-inflammatory genes in vivo. This PK-PD modeling approach may
      provide a conceptual framework for the future clinical evaluation of dietary
      chemopreventive agents in humans.

PMID- 29035549
TI  - Water as a Probe of the Colloidal Properties of Cement.
AB  - Cement is produced by mixing mineral phases based on calcium silicates and
      aluminates with water. The hydration reaction of the mixture leads to a synthetic
      material with outstanding properties that can be used as a binder for
      construction applications. Despite the importance of cement in society, for a
      long time, the chemical reactions involved in its hydration remained poorly
      understood as a result of the complexity of hydration processes, nanostructure,
      and transport phenomena. This feature article reviews the recently obtained
      results using water as a probe to detail the essential features in the setting
      process. By examining the peculiar physicochemical properties of water,
      fundamental information on the evolving inorganic colloid matrix can be deduced,
      ranging from the fractal nanostructure of the inorganic silicate framework to the
      transport phenomena inside the developing porosity. A similar approach can be
      transferred to the investigation of a plethora of other complex systems, where
      water plays the main role in determining the final structural and transport
      properties (i.e., biomaterials, hydrogels, and colloids).

PMID- 29035548
TI  - Enantio- and Diastereoselective Organocatalytic Conjugate Additions of
      Nitroalkanes to Enone Diesters.
AB  - Enantio- and diastereoselective conjugate addition reactions between nitroethane
      or nitropropane and enone diesters are reported. A bifunctional
      triaryliminophosphorane catalyzed the addition reaction with consistently
      excellent stereoselectivities and yields across a wide range of substrates. By
      the use of the gem-diester functional handle present in the adducts, local
      desymmetrization via diastereotopic group discrimination was demonstrated, and a
      polyfunctionalized lactam with three contiguous stereocenters was synthesized.

PMID- 29035550
TI  - Copper-Catalyzed C(sp2)-S Coupling Reactions for the Synthesis of Aryl
      Dithiocarbamates with Thiuram Disulfide Reagents.
AB  - An efficient protocol for the copper-catalyzed preparation of aryl
      dithiocarbamates from aryl iodides and inexpensive, environmentally benign
      tetraalkylthiuram disulfides was developed. The features of mild reaction
      conditions, high yields, and broad substrate scope render this new approach
      synthetically attractive for the preparation of potentially biologically active
      compounds.

PMID- 29035552
TI  - Trion-Species-Resolved Quantum Beats in MoSe2.
AB  - Monolayer photonic materials offer a tremendous potential for on-chip
      optoelectronic devices. Their realization requires knowledge of optical coherence
      properties of excitons and trions that have so far been limited to nonlinear
      optical experiments carried out with strongly inhomogeneously broadened material.
      Here we employ h-BN-encapsulated and electrically gated MoSe2 to reveal coherence
      properties of trion species directly in the linear optical response.
      Autocorrelation measurements reveal long dephasing times up to T2 = 1.16 +/- 0.05
      ps for positively charged excitons. Gate-dependent measurements provide evidence
      that the positively charged trion forms via spatially localized hole states,
      making this trion less prone to dephasing in the presence of elevated hole
      carrier concentrations. Quantum beat signatures demonstrate coherent coupling
      between excitons and trions that have a dephasing time up to 0.6 ps, a 2-fold
      increase over those in previous reports. A key merit of the prolonged
      exciton/trion coherences is that they were achieved in a linear optical
      experiment and thus are directly relevant to applications in nanolasers, coherent
      control, and on-chip quantum information processing requiring long photon
      coherence.

PMID- 29035551
TI  - Improved Phenoxyalkylbenzimidazoles with Activity against Mycobacterium
      tuberculosis Appear to Target QcrB.
AB  - The phenoxy alkyl benzimidazoles (PABs) have good antitubercular activity. We
      expanded our structure-activity relationship studies to determine the core
      components of PABs required for activity. The most potent compounds had minimum
      inhibitory concentrations against Mycobacterium tuberculosis in the low nanomolar
      range with very little cytotoxicity against eukaryotic cells as well as activity
      against intracellular bacteria. We isolated resistant mutants against PAB
      compounds, which had mutations in either Rv1339, of unknown function, or qcrB, a
      component of the cytochrome bc1 oxidase of the electron transport chain. QcrB
      mutant strains were resistant to all PAB compounds, whereas Rv1339 mutant strains
      were only resistant to a subset, suggesting that QcrB is the target. The
      discovery of the target for PAB compounds will allow for the improved design of
      novel compounds to target intracellular M. tuberculosis.

PMID- 29035553
TI  - Construction of Antithrombotic Tissue-Engineered Blood Vessel via Reduced
      Graphene Oxide Based Dual-Enzyme Biomimetic Cascade.
AB  - Thrombosis is one of the biggest obstacles in the clinical application of small
      diameter tissue-engineered blood vessels (TEBVs). The implantation of an
      unmodified TEBV will lead to platelet aggregation and further activation of the
      coagulation cascade, in which the high concentration of adenosine diphosphate
      (ADP) that is released by platelets plays an important role. Inspired by the
      phenomenon that endothelial cells continuously generate endogenous antiplatelet
      substances via enzymatic reactions, we designed a reduced graphene oxide (RGO)
      based dual-enzyme biomimetic cascade to successively convert ADP into adenosine
      monophosphate (AMP) and AMP into adenosine. We used RGO as a support and bound
      apyrase and 5'-nucleotidase (5'-NT) on the surface of RGO through covalent bonds,
      and then, we modified the surface of the collagen-coated decellularized vascular
      matrix with the RGO-enzyme complexes, in which RGO functions as a platform with a
      large open surface area and minimal diffusion barriers for substrates/products to
      integrate two catalytic systems for cascading reactions. The experimental results
      demonstrate that the two enzymes can synergistically catalyze procoagulant ADP
      into anticoagulant AMP and adenosine successively under physiological conditions,
      thus reducing the concentration of ADP. AMP and adenosine can weaken or even
      reverse the platelet aggregation induced by ADP, thereby inhibiting thrombosis.
      Adenosine can also accelerate the endothelialization of TEBVs by regulating
      cellular energy metabolism and optimizing the microenvironment, thus ensuring the
      antithrombotic function and patency of TEBVs even after the RGO-enzyme complex
      loses its activity.

PMID- 29035555
TI  - Removal Mechanisms of Phosphate by Lanthanum Hydroxide Nanorods: Investigations
      using EXAFS, ATR-FTIR, DFT, and Surface Complexation Modeling Approaches.
AB  - Lanthanum-based materials are effective for sequestering phosphate in water,
      however, their removal mechanisms remain unclear, and the effects of
      environmentally relevant factors have not yet been studied. Hereby, this study
      explored the mechanisms of phosphate removal using La(OH)3 by employing extended
      X-ray absorption spectroscopy (EXAFS), attenuated total reflectance Fourier
      transform infrared spectroscopy (ATR-FTIR), density functional theory (DFT) and
      chemical equilibrium modeling. The results showed that surface complexation was
      the primary mechanism for phosphate removal and in binary phosphate
      configurations, namely diprotonated bidentate mononuclear (BM-H2) and bidentate
      binuclear (BB-H2), coexisting on La(OH)3 in acidic conditions. By increasing the
      pH to 7, BM-H1 and BB-H2 were the two major configurations governing phosphate
      adsorption on La(OH)3, whereas BB-H1 was the dominant configuration of phosphate
      adsorption at pH 9. With increasing phosphate loading, the phosphate
      configuration of on La(OH)3 transforms from binary BM-H1 and BB-H2 to BB-H1.
      Amorphous Ca3(PO4)2 forms in the presence of Ca, leading to enhanced phosphate
      removal at alkaline conditions. The contributions of different mechanisms to the
      overall phosphate removal were successfully simulated by a chemical equilibrium
      model that was consistent with the spectroscopic results. This study provides new
      insights into the molecular-level mechanism of phosphate removal by La(OH)3.

PMID- 29035556
TI  - A Theoretical and Mass Spectrometry Study of Dimethyl Methylphosphonate: New
      Isomers and Cation Decay Channels in an Intense Femtosecond Laser Field.
AB  - Using both mass spectrometry with intense femtosecond laser ionization and high
      level computational methods, we have explored the structure and fragmentation
      patterns of dimethyl methylphosphonate (DMMP) cation. Extensive search of the
      geometries of both neutral and positively charged DMMP yields new isomers that
      are appreciably lower in total energy than those commonly synthesized using the
      Michaelis-Arbuzov reaction. The stability of the standard isomer with
      CH3PO(OCH3)2 topology is found to be due to the presence of high barriers to
      isomer interconversion that involves several transition states. Our femtosecond
      laser ionization experiments show that the relative yields of the major
      dissociation products as a function of peak laser intensity correlate well with
      the theoretical estimates for the energies of the DMMP+ decay via various
      channels. In contrast, the peak laser intensities required for observation of
      minor dissociation products exhibit no correlation with the computed decay
      energies, which suggests that barrier heights and/or excited electronic states of
      DMMP+ determine its preferred fragmentation pathways in an intense femtosecond
      laser field.

PMID- 29035554
TI  - Star Polymers Reduce Islet Amyloid Polypeptide Toxicity via Accelerated Amyloid
      Aggregation.
AB  - Protein aggregation into amyloid fibrils is a ubiquitous phenomenon across the
      spectrum of neurodegenerative disorders and type 2 diabetes. A common strategy
      against amyloidogenesis is to minimize the populations of toxic oligomers and
      protofibrils by inhibiting protein aggregation with small molecules or
      nanoparticles. However, melanin synthesis in nature is realized by accelerated
      protein fibrillation to circumvent accumulation of toxic intermediates.
      Accordingly, we designed and demonstrated the use of star-shaped poly(2
      hydroxyethyl acrylate) (PHEA) nanostructures for promoting aggregation while
      ameliorating the toxicity of human islet amyloid polypeptide (IAPP), the peptide
      involved in glycemic control and the pathology of type 2 diabetes. The binding of
      PHEA elevated the beta-sheet content in IAPP aggregates while rendering a new
      morphology of "stelliform" amyloids originating from the polymers. Atomistic
      molecular dynamics simulations revealed that the PHEA arms served as rodlike
      scaffolds for IAPP binding and subsequently accelerated IAPP aggregation by
      increased local peptide concentration. The tertiary structure of the star
      nanoparticles was found to be essential for driving the specific interactions
      required to impel the accelerated IAPP aggregation. This study sheds new light on
      the structure-toxicity relationship of IAPP and points to the potential of
      exploiting star polymers as a new class of therapeutic agents against
      amyloidogenesis.

PMID- 29035558
TI  - Imaging the Hydrogen Absorption Dynamics of Individual Grains in Polycrystalline
      Palladium Thin Films in 3D.
AB  - Defects such as dislocations and grain boundaries often control the properties of
      polycrystalline materials. In nanocrystalline materials, investigating this
      structure-function relationship while preserving the sample remains challenging
      because of the short length scales and buried interfaces involved. Here we use
      Bragg coherent diffractive imaging to investigate the role of structural
      inhomogeneity on the hydriding phase transformation dynamics of individual Pd
      grains in polycrystalline films in three-dimensional detail. In contrast to
      previous reports on single- and polycrystalline nanoparticles, we observe no
      evidence of a hydrogen-rich surface layer and consequently no size dependence in
      the hydriding phase transformation pressure over a 125-325 nm size range. We do
      observe interesting grain boundary dynamics, including reversible rotations of
      grain lattices while the material remains in the hydrogen-poor phase. The
      mobility of the grain boundaries, combined with the lack of a hydrogen-rich
      surface layer, suggests that the grain boundaries are acting as fast diffusion
      sites for the hydrogen atoms. Such hydrogen-enhanced plasticity in the hydrogen
      poor phase provides insight into the switch from the size-dependent behavior of
      single-crystal nanoparticles to the lower transformation pressures of
      polycrystalline materials and may play a role in hydrogen embrittlement.

PMID- 29035557
TI  - Microwave-Facilitated SPOT-Synthesis of Antibacterial Dipeptoids.
AB  - With microwave irradiation, the submonomer synthesis of dipeptoids on
      functionalized cellulose can be accelerated with good yields and purity.
      Optimization provided a library of 96 dipeptoids. From these, 29 compounds were
      found with an antibacterial activity against MRSA at a concentration of 25 MUM.
      Large nonpolar residues, such as undecylamine and dehydroabiethylamine, are the
      key components engendering the observed antibacterial activity of these peptoids.

PMID- 29035559
TI  - Cross-Coupling of Primary Amides to Aryl and Heteroaryl Partners Using
      (DiMeIHeptCl)Pd Promoted by Trialkylboranes or B(C6F5)3.
AB  - Boron-derived Lewis acids have been shown to effectively promote the coupling of
      amide nucleophiles to a wide variety of oxidative addition partners using Pd-NHC
      catalysts. Through a combination of NMR spectroscopy and control studies with and
      without oxygen and radical scavengers, we propose that boron-imidates form under
      the basic reaction conditions that aid coordination of nitrogen to Pd(II), which
      is rate limiting, and directly delivers the intermediate for reductive
      elimination.

PMID- 29035560
TI  - Cytotoxic Dibohemamines D-F from a Streptomyces Species.
AB  - Three dimeric analogues of bohemamines, dibohemamines D-F (1-3), together with
      dibohemamine A (4), were isolated from Streptomyces sp. CPCC 200497. Their
      structures were solved using a combination of mass spectrometry, 1D and 2D NMR
      spectroscopy, and CD. Dibohemamines D and E were new dimeric analogues of
      bohemamines, and dibohemamine F was a known compound obtained previously by
      semisynthesis. Dibohemamine F displayed potent cytotoxicity against cancer cell
      lines A549 and HepG2 with IC50 values of 1.1 and 0.3 MUM, respectively.
      Dibohemamines D and E showed moderate cytotoxicity against cancer cell lines A549
      and HepG2.

PMID- 29035561
TI  - Enhancing Photochemical Internalization of DOX through a Porphyrin-based
      Amphiphilic Block Copolymer.
AB  - Drug resistance is a primary obstacle that seriously reduces the therapy
      efficiency of most chemotherapeutic agents. To address this issue, the
      photochemical internalization (PCI) was employed to help the anticancer drug
      escape from lysosome and improve their translocation to the nucleus. A pH
      sensitive porphyrin-based amphiphilic block copolymer (PEG113-b-PCL54-a
      porphyrin) was synthesized, which was acted not only as a carrier for the
      delivery of DOX but also as a photosensitizer for PCI. PEG113-b-PCL54-a-porphyrin
      as a drug carrier exhibited a higher drug loading capacity, entrapment
      efficiency, and DOX release content. The PCI effect of PEG113-b-PCL54-a-porphyrin
      was studied by confocal laser scanning microscopy, and the results showed that
      most of DOX could be translocated into the nucleus for DOX-loaded PEG113-b-PCL54
      a-porphyrin micelles. Moreover, the IC50 of pH-sensitive DOX-loaded PEG113-b
      PCL54-a-porphyrin micelles was much lower than that of its counterpart without pH
      responsiveness, DOX-loaded PEG113-b-PCL54-porphyrin micelles. Therefore, this
      drug delivery system based on pH-sensitive porphyrin-containing block copolymer
      would act as a potential vehicle for overcoming drug resistance in chemotherapy.

PMID- 29035563
TI  - Kinetic Control of Graphene Localization in Co-continuous Polymer Blends via Melt
      Compounding.
AB  - Selective localization of graphene in co-continuous polymer blends is an
      attractive method for preparing conductive polymer composites. Localization of
      graphene at the interface between the two polymer phases produces good
      conductivity at ultra-low concentrations. Although graphene localization is
      ultimately dependent on thermodynamic factors such as the surface energy of
      graphene and the two polymer components, kinetics also strongly affects the
      migration and localization of graphene in polymer blends during melt compounding.
      However, few studies have systemically investigated the important role of
      kinetics on graphene localization. Here, we introduced graphene nanoplatelets
      (GNPs) in polylactic acid (PLA)/polystyrene (PS) co-continuous polymer blends.
      Although GNPs in thermal equilibrium prefer the PS phase, we were able to
      kinetically trap GNPs at the interface of polymer blends via control of melt
      compounding sequences, mixing times and shear rates. Utilizing morphological,
      rheological, and electrical measurements, we verified graphene localization and
      the suppression of coarsening in co-continuous polymer blends during annealing.
      When GNPs were premixed with the thermodynamically less-favorable PLA phase
      before mixing with the PS phase, GNPs can be kinetically trapped at the interface
      during melt compounding. Moreover, we show that a shorter melt-compounding time
      gives rise to a higher GNP interfacial coverage and a more effective morphology
      stabilization effect. Blends with as low as 0.5 wt % GNPs with only 30 s of melt
      compounding have a room-temperature conductivity of ~10-6 S/cm, which is larger
      than blends with longer melt-compounding times and potentially useful for
      antistatic materials. The in-depth study on the kinetics of graphene localization
      in our work provides a general guideline for the kinetic control of the
      localization of platelike nanofillers in polymer blends. Our study also
      demonstrates a facile method for manufacturing conductive polymer blends with low
      percolation thresholds.

PMID- 29035564
TI  - When Ligand Exchange Leads to Ion Exchange: Nanocrystal Facets Dictate the
      Outcome.
AB  - This study demonstrates that ligand exchange of nanocrystals (NCs) is not always
      an innocuous process, but can lead to facile (room temperature) ion exchange,
      depending on the surface crystal faceting. Rock salt PbTe NCs prepared as cubes
      with neutral facets undergo room-temperature ligand exchange with sulfide ions,
      whereas cuboctahedron-shaped particles with neutral {100} and polar {111} facets
      are transformed to PbS, driven by ion exchange along the ?111? direction.
      Likewise, cation exchange (with Ag+) occurs rapidly for cuboctahedra, whereas
      cubes remain inert. This dramatic difference is attributed to the relative
      surface area of {111} facets that promote rapid ion exchange and shows how facet
      engineering is a powerful knob for the control of reaction pathways in
      nanoparticles.

PMID- 29035565
TI  - Bottom-Up Tri-gate Transistors and Submicrosecond Photodetectors from Guided CdS
      Nanowalls.
AB  - Tri-gate transistors offer better performance than planar transistors by exerting
      additional gate control over a channel from two lateral sides of semiconductor
      nanowalls (or "fins"). Here we report the bottom-up assembly of aligned CdS
      nanowalls by a simultaneous combination of horizontal catalytic vapor-liquid
      solid growth and vertical facet-selective noncatalytic vapor-solid growth and
      their parallel integration into tri-gate transistors and photodetectors at wafer
      scale (cm2) without postgrowth transfer or alignment steps. These tri-gate
      transistors act as enhancement-mode transistors with an on/off current ratio on
      the order of 108, 4 orders of magnitude higher than the best results ever
      reported for planar enhancement-mode CdS transistors. The response time of the
      photodetector is reduced to the submicrosecond level, 1 order of magnitude
      shorter than the best results ever reported for photodetectors made of bottom-up
      semiconductor nanostructures. Guided semiconductor nanowalls open new
      opportunities for high-performance 3D nanodevices assembled from the bottom up.

PMID- 29035562
TI  - Quantification of Membrane Protein-Detergent Complex Interactions.
AB  - Although fundamentally significant in structural, chemical, and membrane biology,
      the interfacial protein-detergent complex (PDC) interactions have been modestly
      examined because of the complicated behavior of both detergents and membrane
      proteins in aqueous phase. Membrane proteins are prone to unproductive
      aggregation resulting from poor detergent solvation, but the participating forces
      in this phenomenon remain ambiguous. Here, we show that using rational membrane
      protein design, targeted chemical modification, and steady-state fluorescence
      polarization spectroscopy, the detergent desolvation of membrane proteins can be
      quantitatively evaluated. We demonstrate that depleting the detergent in the
      sample well produced a two-state transition of membrane proteins between a fully
      detergent-solvated state and a detergent-desolvated state, the nature of which
      depended on the interfacial PDC interactions. Using a panel of six membrane
      proteins of varying hydrophobic topography, structural fingerprint, and charge
      distribution on the solvent-accessible surface, we provide direct experimental
      evidence for the contributions of the electrostatic and hydrophobic interactions
      to the protein solvation properties. Moreover, all-atom molecular dynamics
      simulations report the major contribution of the hydrophobic forces exerted at
      the PDC interface. This semiquantitative approach might be extended in the future
      to include studies of the interfacial PDC interactions of other challenging
      membrane protein systems of unknown structure. This would have practical
      importance in protein extraction, solubilization, stabilization, and
      crystallization.

PMID- 29035566
TI  - Sulfidation of Iron-Based Materials: A Review of Processes and Implications for
      Water Treatment and Remediation.
AB  - Iron-based materials used in water treatment and groundwater remediation
      especially micro- and nanosized zerovalent iron (nZVI)-can be more effective when
      modified with lower-valent forms of sulfur (i.e., "sulfidated"). Controlled
      sulfidation for this purpose (using sulfide, dithionite, etc.) is the main topic
      of this review, but insights are derived by comparison with related and
      comparatively well-characterized processes such as corrosion of iron in sulfidic
      waters and abiotic natural attenuation by iron sulfide minerals. Material
      characterization shows that varying sulfidation protocols (e.g., concerted or
      sequential) and key operational variables (e.g., S/Fe ratio and sulfidation
      duration) result in materials with structures and morphologies ranging from core
      shell to multiphase. A meta-analysis of available kinetic data for dechlorination
      under anoxic conditions, shows that sulfidation usually increases dechlorination
      rates, and simultaneously hydrogen production is suppressed. Therefore,
      sulfidation can greatly improve the efficiency of utilization of reducing
      equivalents for contaminant removal. This benefit is most likely due to inhibited
      corrosion as a result of sulfidation. Sulfidation may also favor desirable
      pathways of contaminant removal, such as (i) dechlorination by reductive
      elimination rather than hydrogenolysis and (ii) sequestration of metals as
      sulfides that could be resistant to reoxidation. Under oxic conditions,
      sulfidation is shown to enhance heterogeneous catalytic oxidation of
      contaminants. These net effects of sulfidation on contaminant removal by iron
      based materials may substantially improve their practical utility for water
      treatment and remediation of contaminated groundwater.

PMID- 29035567
TI  - Hit-to-Lead Optimization and Discovery of 5-((5-([1,1'-Biphenyl]-4-yl)-6-chloro
      1H-benzo[d]imidazol-2-yl)oxy)-2-methylbenzoic Acid (MK-3903): A Novel Class of
      Benzimidazole-Based Activators of AMP-Activated Protein Kinase.
AB  - AMP-activated protein kinase (AMPK) plays an essential role as a cellular energy
      sensor and master regulator of metabolism in eukaryotes. Dysregulated lipid and
      carbohydrate metabolism resulting from insulin resistance leads to hyperglycemia,
      the hallmark of type 2 diabetes mellitus (T2DM). While pharmacological activation
      of AMPK is anticipated to improve these parameters, the discovery of selective,
      direct activators has proven challenging. We now describe a hit-to-lead effort
      resulting in the discovery of a potent and selective class of benzimidazole-based
      direct AMPK activators, exemplified by 5-((5-([1,1'-biphenyl]-4-yl)-6-chloro-1H
      benzo[d]imidazol-2-yl)oxy)-2-methylbenzoic acid, 42 (MK-3903). Compound 42
      exhibited robust target engagement in mouse liver following oral dosing, leading
      to improved lipid metabolism and insulin sensitization in mice.

PMID- 29035568
TI  - Triplet-State Dissolved Organic Matter Quantum Yields and Lifetimes from Direct
      Observation of Aromatic Amine Oxidation.
AB  - Excited triplet state chromophoric dissolved organic matter (3CDOM*) is a short
      lived mixture of excited-state species that plays important roles in aquatic
      photochemical processes. Unlike the study of the triplet states of well-defined
      molecules, which are amenable to transient absorbance spectroscopy, the study of
      3CDOM* is hampered by it being a complex mixture and its low average intersystem
      crossing quantum yield (PhiISC). This study is an alternative approach to
      investigating 3CDOM* using transient absorption laser spectroscopy. The radical
      cation of N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), formed through
      oxidation by 3CDOM*, was directly observable by transient absorption spectroscopy
      and was used to probe basic photophysical properties of 3CDOM*. Quenching and
      control experiments verified that TMPD*+ was formed from 3CDOM* under anoxic
      conditions. Model triplet sensitizers with a wide range of excited triplet state
      reduction potentials and CDOM oxidized TMPD at near diffusion-controlled rates.
      This gives support to the idea that a large cross-section of 3CDOM* moieties are
      able to oxidize TMPD and that the complex mixture of 3CDOM* can be simplified to
      a single signal. Using the TMPD*+ transient, the natural triplet lifetime and
      PhiISC for different DOM isolates and natural waters were quantified; values
      ranged from 12 to 26 MUs and 4.1-7.8%, respectively.

PMID- 29035569
TI  - Digest.

PMID- 29035570
TI  - A Median Solver and Phylogenetic Inference Based on Double-Cut-and-Join Sorting.
AB  - Genome rearrangement is known as one of the main evolutionary mechanisms on the
      genomic level. Phylogenetic analysis based on rearrangement played a crucial role
      in biological research in the past decades, especially with the increasing
      availability of fully sequenced genomes. In general, phylogenetic analysis aims
      to solve two problems: small parsimony problem (SPP) and big parsimony problem
      (BPP). Maximum parsimony is a popular approach for SPP and BPP, which relies on
      iteratively solving an NP-hard problem, the median problem. As a result, current
      median solvers and phylogenetic inference methods based on the median problem all
      face serious problems on scalability and cannot be applied to data sets with
      large and distant genomes. In this article, we propose a new median solver for
      gene order data that combines double-cut-and-join sorting with the simulated
      annealing algorithm. Based on this median solver, we built a new phylogenetic
      inference method to solve both SPP and BPP problems. Our experimental results
      show that the new median solver achieves an excellent performance on simulated
      data sets, and the phylogenetic inference tool built based on the new median
      solver has a better performance than other existing methods.

PMID- 29035571
TI  - Flavonoids in fruits and vegetables after thermal and nonthermal processing: A
      review.
AB  - Consumers currently demand more nutritious food, which is minimally processed and
      naturally produced. Flavonoids are one of the major plant metabolites found
      throughout the plant kingdom, especially in fruits and vegetables. Flavonoids
      exert tremendous positive effects on health and protect against various diseases.
      Fruits and vegetables are difficult to store for a long period, owing to their
      perishable nature even at low temperatures. Therefore, processing is necessary to
      prolong their shelf lives and increase nutritional values. Thermal processing has
      been used in the food sector since ancient times. However, nonthermal processing
      has become more attractive to consumers and product developers recently, owing to
      the retention of beneficial health properties after nonthermal processing. The
      present review will address the effects of thermal and nonthermal processing
      methods such as blanching, drying, high-pressure processing, ultrasound, pulsed
      electric field, and ultraviolet irradiation on total and individual flavonoid
      content in fruits and vegetables. In addition, this text will elucidate the
      stability characteristics as well as bioavailability, cytotoxicity, and
      transformations of flavonoids during thermal and nonthermal treatments.

PMID- 29035572
TI  - Maintaining and Enhancing Diversity of Sampled Protein Conformations in Robotics
      Inspired Methods.
AB  - The ability to efficiently sample structurally diverse protein conformations
      allows one to gain a high-level view of a protein's energy landscape. Algorithms
      from robot motion planning have been used for conformational sampling, and
      several of these algorithms promote diversity by keeping track of "coverage" in
      conformational space based on the local sampling density. However, large proteins
      present special challenges. In particular, larger systems require running many
      concurrent instances of these algorithms, but these algorithms can quickly become
      memory intensive because they typically keep previously sampled conformations in
      memory to maintain coverage estimates. In addition, robotics-inspired algorithms
      depend on defining useful perturbation strategies for exploring the
      conformational space, which is a difficult task for large proteins because such
      systems are typically more constrained and exhibit complex motions. In this
      article, we introduce two methodologies for maintaining and enhancing diversity
      in robotics-inspired conformational sampling. The first method addresses
      algorithms based on coverage estimates and leverages the use of a low-dimensional
      projection to define a global coverage grid that maintains coverage across
      concurrent runs of sampling. The second method is an automatic definition of a
      perturbation strategy through readily available flexibility information derived
      from B-factors, secondary structure, and rigidity analysis. Our results show a
      significant increase in the diversity of the conformations sampled for proteins
      consisting of up to 500 residues when applied to a specific robotics-inspired
      algorithm for conformational sampling. The methodologies presented in this
      article may be vital components for the scalability of robotics-inspired
      approaches.

PMID- 29035573
TI  - Field-based investigation on phytoremediation potentials of Lemna minor and
      Azolla filiculoides in tropical, semiarid regions: Case of Ethiopia.
AB  - This study investigated the concurrent accumulation of eight heavy metals by two
      floating aquatic macrophytes (Lemna minor and Azolla filiculoides) cultivated in
      ambient media and blended wastewaters in the semiarid regions of Ethiopia. Both
      species accumulated heavy metals in varying degrees with a significant
      concentration gradient within the immediate water media. Highest bioconcentration
      factor (BCF) was determined for Mn and Fe in both plants. Results revealed that
      L. minor was high phytoaccumulator for Fe, Mn, Zn, and Co but moderate for Cd,
      Cu, Ni, and Cr. On the other hand, A. filiculoides was a high accumulator for Fe,
      Mn, Zn, and Cu, but its potency was moderate for Co, Cr, and Ni, but lower for
      Cd. Both species exhibited significant difference in accumulating Co, Zn, and Mn
      (p < 0.05). In general, the BCFs for both plants were comparable within the same
      treatment. In this study, stronger associations between the heavy metal
      concentrations in the plant tissues and in the grown water media were observed
      for A. filiculoides.

PMID- 29035575
TI  - HetFHMM: A Novel Approach to Infer Tumor Heterogeneity Using Factorial Hidden
      Markov Models.
AB  - Cancer arises from successive rounds of mutations, resulting in tumor cells with
      different somatic mutations known as clones. Drug responsiveness and therapeutics
      of cancer depend on the accurate detection of clones in a tumor sample. Recent
      research has considered inferring clonal composition of a tumor sample using
      computational models based on short read data of the sample generated using next
      generation sequencing (NGS) technology. Short reads (segmented DNA parts of
      different tumor cells) are noisy; therefore, inferring the clones and their
      mutations from the data is a difficult and complex problem. We develop a new
      model called HetFHMM, based on factorial hidden Markov models, to infer clones
      and their proportions from noisy NGS data. In our model, each hidden chain
      represents the genomic signature of a clone, and a mixture of chains results in
      the observed data. We make use of Gibbs sampling and exponentiated gradient
      algorithms to infer the hidden variables and mixing proportions. We compare our
      model with strong models from previous work (PyClone and PhyloSub) based on both
      synthetic data and real cancer data on acute myeloid leukemia. Empirical results
      confirm that HetFHMM infers clonal composition of a tumor sample more accurately
      than previous work.

PMID- 29035574
TI  - A 6-Month Open-Label Extension Study of Vortioxetine in Pediatric Patients with
      Depressive or Anxiety Disorders.
AB  - OBJECTIVES: In this 6-month open-label extension (OLE) of NCT01491035 (a 14-day,
      open-label, pharmacokinetic/safety lead-in study), the long-term safety and
      tolerability of vortioxetine (5-20 mg/day) were investigated in children and
      adolescents with a DSM-IV-TRTM diagnosis of depressive or anxiety disorder in the
      United States or Germany. The study also was designed to provide data to inform
      dose selection and titration in future pediatric studies with vortioxetine.
      METHODS: Safety evaluations included spontaneously reported adverse events (AEs),
      the Columbia Suicide Severity Rating Scale (C-SSRS), and the Pediatric Adverse
      Events Rating Scale (PAERS; clinician administered). Clinical effectiveness was
      determined by Clinical Global Impressions. Comorbid attention
      deficit/hyperactivity disorder was permitted, including concomitant use of
      stimulant medication (US sites only). RESULTS: Of the 47 patients who completed
      the lead-in period, 41 continued into the OLE. Most patients (n = 39 [95%])
      continued their previous dose regimen. Twenty-one patients (51%) withdrew during
      the OLE; the most common primary reasons were administrative [n = 8], AEs [n =
      4], and lack of efficacy [n = 3]. Thirty-five patients (85%) had >=1 AE, 86% of
      which were mild or moderate in severity. Five patients (12%) reported a severe
      AE, none of which was considered related to study medication. The most common AEs
      (>=10%) were headache (27%), nausea (20%), dysmenorrhea (females; 19%), and
      vomiting (15%), with no relationship between AE intensity and age or dose. Five
      patients reported instances of suicidal ideation during the OLE, one of whom also
      reported this during the lead-in period. Two patients had nonsuicidal self
      injurious behavior; one had a nonfatal suicide attempt. Throughout the study,
      there was a decrease over time in the incidence and intensity of AEs collected
      using the PAERS. Effectiveness assessment indicated a trend toward improvement
      based on numeric results. CONCLUSION: This OLE confirms the findings from the
      lead-in study, which concluded that a dosing strategy of 5-20 mg/day is safe,
      well tolerated, and suitable for future clinical studies of vortioxetine in
      pediatric patients.

PMID- 29035576
TI  - Inter- and Intrarater Reliabilities of the Test of Gross Motor Development-Third
      Edition Among Experienced TGMD-2 Raters.
AB  - The purpose of this study was to examine the inter- and intrarater reliabilities
      of the Test of Gross Motor Development-third edition (TGMD-3). The TGMD-3 was
      administered to 10 typically developing children. Five raters with experience
      using the Test of Gross Motor Development-second edition (TGMD-2) scored the
      digitally recorded performances and then rescored the same performances after a
      period of 2 weeks. Intraclass correlation (ICC) was used to examine both inter-
      and intrarater reliabilities of scores. Interrater reliability for the total
      score, locomotor subscale, and ball skills subscale (ICC: 0.92-0.96) were all
      excellent, while individual skills (ICC: 0.51-0.93) had fair-to-excellent
      reliability. Intrarater reliability across all raters was also excellent (ICC:
      0.77-0.98) but varied widely for individual raters (ICC: 0.28-1.00) including
      multiple examples of poor reliability. While raters experienced with the TGMD-2
      can produce consistent scores for TGMD-3 total scale and subscales, additional
      training is needed to improve skill-specific reliability.

PMID- 29035578
TI  - Load Monitoring Variables in Training and Competition Situations: A Systematic
      Review Applied to Wheelchair Sports.
AB  - The aim of this review was to identify the main variables for load monitoring in
      training and competition situations in wheelchair sports. Studies were identified
      from a systematic search of three databases (PubMed, Web of Science, and
      SportDiscuss), with search phrases constructed from MeSH terms, alone or in
      combination, limited to English-language literature, and published up to January
      2016. Our main findings were that variables related to external load (distance,
      speed, and duration) are used to monitor load in competition. In training
      situations, researchers have used variables related to internal load (heart rate
      and VO2); in both training and competition situations, researchers used internal
      load measurements (training impulse and ratings of perceived exertion). We
      conclude that the main variables for load monitoring in competitive situations
      were distance, speed, and duration, whereas the variables for training situations
      were heart rate, VO2, training impulse, and ratings of perceived exertion.

PMID- 29035579
TI  - Beta-Barrel Detection for Medium Resolution Cryo-Electron Microscopy Density Maps
      Using Genetic Algorithms and Ray Tracing.
AB  - Cryo-electron microscopy (cryo-EM) is a technique that produces three-dimensional
      density maps of large protein complexes. This allows for the study of the
      structure of these proteins. Identifying the secondary structures within proteins
      is vital to understanding the overall structure and function of the protein. The
      [Formula: see text]-barrel is one such secondary structure, commonly found in
      lipocalins and membrane proteins. In this article, we present a novel approach
      that utilizes genetic algorithms, kd-trees, and ray tracing to automatically
      detect and extract [Formula: see text]-barrels from cryo-EM density maps. This
      approach was tested on simulated and experimental density maps with zero, one, or
      multiple barrels in the density map. The results suggest that the proposed
      approach is capable of performing automatic detection of [Formula: see text]
      barrels from medium resolution cryo-EM density maps.

PMID- 29035580
TI  - Mutation Sensitivity Maps: Identifying Residue Substitutions That Impact Protein
      Structure Via a Rigidity Analysis In Silico Mutation Approach.
AB  - Understanding how an amino acid substitution affects a protein's structure can
      aid in the design of pharmaceutical drugs that aim at countering diseases caused
      by protein mutants. Unfortunately, performing even a few amino acid substitutions
      in vitro is both time and cost prohibitive, whereas an exhaustive analysis that
      involves systematically mutating all amino acids in the physical protein is
      infeasible. Computational methods have been developed to predict the effects of
      mutations, but even many of them are computationally intensive or are else
      dependent on homology or experimental data that may not be available for the
      protein being studied. In this work, we motivate and present a computation
      pipeline whose only input is a Protein Data Bank file containing the 3D
      coordinates of the atoms of a biomolecule. Our high-throughput approach uses our
      ProMuteHT algorithm to exhaustively generate in silico amino acid substitutions
      at each residue, and it also includes an energy minimization option. This is in
      contrast to our previous work, where we analyzed the effects of in silico
      mutations to Alanine, Serine, and Glycine only. We exploit the speed of a fast
      rigidity analysis approach to analyze our protein variants, and develop a
      Mutation Sensitivity (MuSe) Map, to permit identifying residues that are most
      sensitive to mutations. We present a case study to show the degree to which a
      MuSe Map and whisker plots are able to locate amino acids whose mutations most
      affect a protein's structure as inferred from a rigidity analysis approach.

PMID- 29035581
TI  - Gene Expression as a Dosimeter in Irradiated Drosophila melanogaster.
AB  - Biological indicators would be of use in radiation dosimetry in situations where
      an exposed person is not wearing a dosimeter, or when physical dosimeters are
      insufficient to estimate the risk caused by the radiation exposure. In this work,
      we investigate the use of gene expression as a dosimeter. Gene expression
      analysis was done on 15,222 genes of Drosophila melanogaster (fruit flies) at
      days 2, 10, and 20 postirradiation, with X-ray exposures of 10, 1000, 5000,
      10,000, and 20,000 roentgens. Several genes were identified, which could serve as
      a biodosimeter in an irradiated D. melanogaster model. Many of these genes have
      human homologues. Six genes showed a linear response (R2 > 0.9) with dose at all
      time points. One of these genes, inverted repeat-binding protein, is a known DNA
      repair gene and has a human homologue (XRCC6). The lowest dose, 10 roentgen, is
      very low for fruit flies. If the lowest dose is excluded, 13 genes showed a
      linear response with dose at all time points. This includes 5 of 6 genes that
      were linear with all radiation doses included. Of these 13 genes, 4 have human
      homologues and 8 have known functions. The expression of this panel of genes,
      particularly those with human homologues, could potentially be used as the
      biological indicator of radiation exposure in dosimetry applications.

PMID- 29035582
TI  - Video Feedback and 2-Dimensional Landing Kinematics in Elite Female Handball
      Players.
AB  - CONTEXT:   In team handball, an anterior cruciate ligament injury often occurs
      during landing after a jump shot. Many intervention programs try to reduce the
      injury rate by instructing athletes to land more safely. Video is an effective
      way to provide feedback, but little is known about its influence on landing
      technique in sport-specific situations. OBJECTIVE:   To test the effectiveness of
      a video-overlay feedback method on landing technique in elite handball players.
      DESIGN:   Controlled laboratory study. SETTING:   Laboratory. PATIENTS OR OTHER
      PARTICIPANTS:   A total of 16 elite female handball players assigned to a control
      group (n = 8; age = 17.61 +/- 1.34 years, height = 1.73 +/- 0.06 m, mass = 69.55
      +/- 4.29 kg) or video group (n = 8; age = 17.81 +/- 0.86 years, height = 1.71 +/-
      0.03 m, mass = 64.28 +/- 6.29 kg). INTERVENTION(S):   Both groups performed jump
      shots in a pretest, 2 training sessions, and a posttest. The video group received
      video feedback of an expert model with an overlay of their own jump shots in
      training sessions 1 and 2, whereas the control group did not. MAIN OUTCOME
      MEASURE(S):   We measured ankle, knee, and hip angles in the sagittal plane at
      initial contact and peak flexion; range of motion; and Landing Error Scoring
      System (LESS) scores. One 2 * 4 repeated-measures analysis of variance was
      conducted to analyze the group, time, and interaction effects of all kinematic
      outcome measures and the LESS score. RESULTS:   The video group improved knee and
      hip flexion at initial contact and peak flexion and range of motion. In addition,
      the group's average peak ankle flexion (12.0 degrees  at pretest to 21.8 degrees 
      at posttest) and LESS score (8.1 pretest to 4.0 posttest) improved. When we
      considered performance variables, no differences between groups were found in
      shot accuracy or vertical jump height, whereas horizontal jump distance in the
      video group increased over time. CONCLUSIONS:   Overlay visual feedback is an
      effective method for improving landing kinematics during a sport-specific jump
      shot. Further research is warranted to determine the long-term effects and
      transfer to training and game situations.

PMID- 29035583
TI  - Resveratrol Suppresses Growth and Migration of Myelodysplastic Cells by
      Inhibiting the Expression of Elevated Cyclin D1 (CCND1).
AB  - Myelodysplastic syndromes (MDS) are a group of heterogeneous diseases
      characterized by poorly formed blood cells. We wanted to elucidate the underlying
      molecular mechanism to better determine pathogenesis, prognosis, diagnosis, and
      treatment for patients with MDS. We compared gene expression levels between
      normal and MDS tissue samples by immunohistochemical analysis. We studied the
      proliferation, survival, and migration of MDS cells using the EDU assay, colony
      formation, and transwell assays. We assessed the apoptotic rate and cell cycle
      status using flow cytometry and Hoechst staining. Finally, we evaluated RNA and
      protein expressions using polymerase chain reaction and Western blots,
      respectively. We found that resveratrol suppressed SKM-1 (an advanced MDS cell
      line) proliferation in a dose-dependent manner. Consistent with this finding, the
      EDU and colony formation assays also showed that resveratrol inhibited SKM-1
      growth. Moreover, flow cytometry and Hoechst 33258 staining demonstrated that
      resveratrol induced apoptosis and a change in cell cycle status in SKM-1 cells,
      while the transwell assay showed that resveratrol reduced the migratory ability
      of SKM-1 cells. Resveratrol also decreased the expression of CCND1 (a gene that
      encodes the cyclin D1 protein) and increased expressions of KMT2A [lysine (K)
      specific methyltransferase 2A] and caspase-3, suggesting that resveratrol exerts
      its effect by regulating CCND1 in SKM-1 cells. In addition, a combination of
      resveratrol and the PI3K/AKT inhibitor LY294002 exhibited a stronger inhibitory
      effect on the SKM-1 cells, compared with resveratrol alone. Our study proved that
      resveratrol suppresses SKM-1 growth and migration by inhibiting CCND1 expression.
      This finding provides novel insights into the pathogenesis of MDS and might help
      develop new diagnosis and treatment for patients with MDS.

PMID- 29035584
TI  - Hybrid Fixation for Ankle Fusion in Diabetic Charcot Arthropathy.
AB  - BACKGROUND: Ankle fusion is difficult to achieve in the diabetic Charcot ankle
      Brodsky type 3a because of the poor quality of the bone and the inability to
      achieve a stable biomechanical construct. The aim of this study was to report the
      outcome of ankle fusion using a combination of an intramedullary nail and a
      circular external fixator in patients with diabetic Charcot arthropathy. METHODS:
      We prospectively studied 24 patients with diabetic Charcot arthropathy of the
      ankle who were treated by fusion of the tibiotalar joint using a combined
      retrograde intramedullary nail and Ilizarov external fixator. Their mean age was
      50.7 +/- 6.9 (range, 43-62) years. The mean follow-up after surgery was 36.4 +/-
      5.8 (range, 24-98) months. RESULTS: Twenty-two patients (92%) achieved clinical
      and radiographic solid bony fusion. No patients in this series needed amputation.
      All the patients were pain free, and the mean American Orthopaedic Foot & Ankle
      Society Score (AOFAS) improved significantly from 34.6 +/- 6.8 to 66.4 +/- 4.5 at
      the last follow-up. Two patients developed an ulcer over the heel due to a
      prominent nail. The ulcer healed after nail removal. Eight patients developed pin
      tract infection. CONCLUSION: We report a successful outcomes of ankle fusions
      using combined intramedullary nail locked only proximally and ring external
      fixator (hybrid fixation) in patients with diabetic Charcot arthropathy. LEVEL OF
      EVIDENCE: Level IV, case series.

PMID- 29035586
TI  - Hemoconcentration During Maximum Exercise in Miners with Chronic Intermittent
      Exposure to Hypobaric Hypoxia (3800 m).
AB  - : Moraga, Fernando A., Jorge Osorio, Rodrigo Calderon-Jofre, and Andres Pedreros.
      Hemoconcentration during maximum exercise in miners with chronic intermittent
      exposure to hypobaric hypoxia (3800 m). High Alt Med Biol. 19:15-20, 2018.
      OBJECTIVE: To evaluate the effect of maximum exercise on hemoconcentration in
      miners with chronic intermittent hypobaric hypoxia (CIHH) at 3800 m. MATERIALS
      AND METHODS: Sixteen miners with CIHH at high altitude (3800 m) were subjected to
      maximum exercise levels on a cycle ergometer, increasing exercise load by 50 W
      every 3 minutes at sea level and high altitude (3800 m). During exercise,
      arterial oxygen saturation and heart rate were measured. Blood samples were taken
      at each step to measure hemoglobin concentration and hematocrit. Arterial blood
      oxygen content was also calculated. RESULTS: At sea level, a decrease in arterial
      oxygen saturation to 92.1% +/- 2.5% was observed at 150 W and the hematocrit,
      hemoglobin concentration and oxygen content were not altered. At high altitude,
      arterial oxygen saturation decreased, reaching 88.2% +/- 4.9% at 50 W and
      remained constant during the entire exercise protocol. Hemoglobin concentration
      and hematocrit increased reaching 16.4 +/- 0.9 g/dL and 48.8% +/- 1.6%,
      respectively, at 100 W and were maintained until recovery. Arterial oxygen
      content was constant during exercise and increased in the recovery period.
      CONCLUSION: An increase in hemoglobin concentration during exercise compensates
      for the decline in arterial oxygen saturation, meanwhile arterial oxygen content
      remains constant.

PMID- 29035587
TI  - Computer-Aided Stroke-by-Stroke Visualization of Actual and Target Power Allows
      for Continuously Increasing Ramp Tests on Wind-Braked Rowing Ergometers.
AB  - PURPOSE: Ramp tests are continuously increasing exercise tests used for the
      determination of maximal oxygen uptake ( V  O 2 max ), which is identifiable by a
      plateau in oxygen uptake despite increasing mechanical power output (LOAD). On
      wind-braked rowing ergometers (RowErg), it is hardly feasible to ensure a
      continuous increase in LOAD until test termination, as neither resistance nor
      stroke frequency is externally adjustable but depends on the rower. To enable
      ramp tests on RowErg, the authors produced visual stroke-by-stroke feedback
      showing target and actual LOAD to the rower. The software supports automatic test
      termination (TERMauto) if LOAD ceases to increase. The authors aimed to evaluate
      linearity of the LOAD increment and calculate the difference between TERMauto and
      test duration at subjective exhaustion. MATERIALS: Twenty-eight highly trained
      male rowers performed a ramp test until subjective exhaustion on RowErg,
      targeting an increment of 35 W.min-1. LOAD was measured as work per time via
      external force and position sensors and visualized on a computer screen. TERMauto
      was deactivated, but all data were logged. Test duration at subjective exhaustion
      was subsequently compared with virtual test duration at TERMauto calculated from
      the log files. RESULTS: Regression between time and LOAD was y = 167 + 34.6 W (r
      = .99). Individual correlations ranged from .97 to 1.0. TERMauto caused 12- to 35
      s-shorter test durations than subjective exhaustion in 4 rowers, leading to an
      underestimation in V  O 2 max not higher than 1.2% or 3.7%. CONCLUSION: This
      setup allows one to perform ramp tests on RowErg with continuously increasing
      LOAD until TERMauto. In particular cases V  O 2 max might be slightly
      underestimated at TERMauto.

PMID- 29035588
TI  - External Match Loads of Footballers With Cerebral Palsy: A Comparison Among Sport
      Classes.
AB  - PURPOSE: To determine and compare the external match load, according to sport
      class (FT), of footballers with cerebral palsy (CP) during the International
      Federation of CP Football World Championships Qualification Tournament. METHODS:
      Forty-two international male footballers with CP participated in the data
      collection. The footballers with CP were classified according to their FT into 3
      groups (ie, FT5/6, FT7, and FT8). External match load (ie, total distance
      covered, distance covered at different speeds, accelerations, decelerations,
      player load, peak metabolic power, and changes of directions) was collected for
      both halves during official matches with global positioning system devices.
      RESULTS: Players with lower impairment (FT8) covered more distance (effect size =
      0.30-0.60) at high-intensity running (13.0-18.0 km.h-1) and sprinting (>18.0 km.h
      1) and performed more (effect size = 0.29-1.08) accelerations, decelerations, and
      changes of direction at high intensity in matches than did other players (ie,
      FT5/6 and FT7 groups). CONCLUSION: Because high-intensity actions are relevant to
      football performance and there are differences caused by players' impairments,
      the International Federation of CP Football classification protocols should
      include high-intensity actions during the technical assessment as part of the
      procedures for determining the sport class of football players with CP.

PMID- 29035589
TI  - The activity of nintedanib in an animal model of allogenic left lung
      transplantation resembling aspects of allograft rejection.
AB  - AIM OF THE STUDY: The prevention and treatment of chronic lung allograft
      dysfunction (CLAD) after lung transplantation (LTx) remain unsatisfactory. Growth
      factors may play an important role in the development of CLAD. This study
      evaluated the effects of nintedanib, a receptor tyrosine kinase inhibitor, in the
      treatment of CLAD after experimental LTx. MATERIALS AND METHODS: A rat model of
      left lung allo-transplantation (Fisher 344 to Wistar Kyoto) was used to evaluate
      the effect of nintedanib (50 mg/kg per day) on the development of CLAD. Therapy
      with nintedanib began 2 days before LTx and ended on postoperative day (POD) 20
      (n = 6) or 60 (n = 6). Nontreated animals who underwent LTx (n = 12) were used as
      controls, whereas naive lungs (n = 24) served as reference for physiological
      healthy organs without transplantation damage or medical effects. Acute and
      chronic rejection were evaluated on POD 20 and 60, respectively. RESULTS:
      Immunohistologic analysis showed a decrease in growth factors/receptors on POD 60
      (nintedanib-treated vs. nontreated controls: platelet-derived growth factor
      (PDGF) A: [P <= 0.001]; PDGF receptor-alpha: [P <= 0.001]; vascular endothelial
      growth factor (VEGF) A: [P <= 0.001]; VEGF receptor-2: [P <= 0.001]). However, no
      reductions in fibrotic changes were observed in nintedanib-treated allografts
      compared with nontreated allografts. Although nintedanib treatment started before
      LTx none of the animals showed impaired wound healing. No dehiscence of the
      sutures of the bronchus, vessels or skin, or stenosis of the bronchus was found.
      CONCLUSION: In conclusion, while nintedanib reduced the expression of growth
      factors/receptors in a rat LTx model, a reduction in fibrotic alterations was not
      observed at POD 60.

PMID- 29035590
TI  - The Impact of Different Competitive Environments on Pacing and Performance.
AB  - PURPOSE: In real-life competitive situations, athletes are required to
      continuously make decisions about how and when to invest their available energy
      resources. This study attempted to identify how different competitive
      environments invite elite short-track speed skaters to modify their pacing
      behavior during head-to-head competition. METHODS: Lap times of elite 500-, 1000-
      and 1500-m short-track speed skating competitions between 2011 and 2016 (N =
      34,095 races) were collected. Log-transformed lap and finishing times were
      analyzed with mixed linear models. The fixed effects in the model were sex,
      season, stage of competition, start position, competition importance, event
      number per tournament, number of competitors per race, altitude, and time
      qualification. The random effects of the model were athlete identity and the
      residual (within-athlete race-to-race variation). Separate analyses were
      performed for each event. RESULTS: Several competitive environments, such as the
      number of competitors in a race (a higher number of competitors evoked most
      likely a faster initial pace; coefficient of variation [CV] = 1.9-9.3%), the
      stage of competition (likely to most likely, a slower initial pace was
      demonstrated in finals; CV = -1.4% to 2.0%), the possibility of time
      qualification (most likely a faster initial pace; CV = 2.6-5.0%), and competition
      importance (most likely faster races at the Olympics; CV = 1.3-3.5%), altered the
      pacing decisions of elite skaters in 1000- and 1500-m events. Stage of
      competition and start position affected 500-m pacing behavior. CONCLUSIONS: As
      demonstrated in this study, different competitive environments evoked
      modifications in pacing behavior, in particular in the initial phase of the race,
      emphasizing the importance of athlete-environment interactions, especially during
      head-to-head competitions.

PMID- 29035591
TI  - Effect of Intensified Endurance Training on Pacing and Performance in 4000-m
      Cycling Time Trials.
AB  - Studies examining pacing strategies during 4000-m cycling time trials (TTs)
      typically ensure that participants are not prefatigued; however, competitive
      cyclists often undertake TTs when already fatigued. This study aimed to determine
      how TT pacing strategies and sprint characteristics of cyclists change during an
      intensified training period (mesocycle). Thirteen cyclists regularly competing in
      A- and B-grade cycling races and consistently training (>10 h/wk for 4 [1] y)
      completed a 6-wk training mesocycle. Participants undertook individually
      prescribed training, using training stress scores (TrainingPeaks, Boulder, CO),
      partitioned into a baseline week, a build week, 2 loading weeks (designed to
      elicit an overreached state), and 2 recovery weeks. Laboratory-based tests (15-s
      sprint and TT) and Recovery-Stress Questionnaire (RESTQ-52) responses were
      repeatedly undertaken over the mesocycle. TT power output increased during
      recovery compared with baseline and loading weeks (P = .001) with >6-W increases
      in mean power output (MPO) detected for 400-m sections (10% bins) from 1200 to
      4000 m in recovery weeks. Decreases in peak heart rate (P < .001) during loading
      weeks and postexercise blood lactate (P = .005) during loading week 2 and
      recovery week 1 were detected. Compared with baseline, 15-s sprint MPO declined
      during loading and recovery weeks (P < .001). An interaction was observed between
      RESTQ-52 total stress score with a 15-s sprint (P = .003) and with a TT MPO (P =
      .04), indicating that participants who experienced greater stress during loading
      weeks exhibited reduced performance. To conclude, intensified endurance training
      diminished sprint performance but improved 4000-m TT performance, with a subtle
      change in MPO evident over the last 70% of TTs.

PMID- 29035592
TI  - Returners Exhibit Greater Jumping Performance Improvements During a Peaking Phase
      Compared With New Players on a Volleyball Team.
AB  - PURPOSE: To determine if jumping-performance changes during a peaking phase
      differed among returners and new players on a female collegiate volleyball team
      and to determine which variables best explained the variation in performance
      changes. METHODS: Fourteen volleyball players were divided into 2 groups
      returners (n = 7) and new players (n = 7)-who completed a 5-wk peaking phase
      prior to conference championships. Players were tested at baseline before the
      preseason on measures of the vastus lateralis cross-sectional area using
      ultrasonography, estimated back-squat 1-repetition maximum, countermovement jump
      height (JH), and relative peak power on a force platform. Jumping performance,
      rating of perceived exertion training load, and sets played were recorded weekly
      during the peaking phase. RESULTS: There were moderate to very large (P < .01,
      Glass Delta = 1.74) and trivial to very large (P = .07, Delta = 1.09) differences
      in JH and relative peak power changes in favor of returners over new players,
      respectively, during the peaking phase. Irrespective of group, 7 of 14 players
      achieved peak JH 2 wk after the initial overreach. The number of sets played (r =
      .78, P < .01) and the athlete's preseason relative 1-repetition maximum (r = .54,
      P = .05) were the strongest correlates of JH changes during the peaking phase.
      CONCLUSIONS: Returners achieved greater improvements in jumping performance
      during the peaking phase compared with new players, which may be explained by the
      returners' greater relative maximal strength, time spent competing, and training
      experience. Thus, volleyball and strength coaches should consider these factors
      when prescribing training during a peaking phase to ensure their players are
      prepared for important competitions.

PMID- 29035593
TI  - The Impact of Body Mass Index and Waist Circumference on Health-related Quality
      of Life Among Colorectal Cancer Survivors: Results from the PROFILES Registry.
AB  - BACKGROUND: We aimed to assess the association of waist circumference (WC) and
      body mass index (BMI) with health-related quality of life (HRQL) among colorectal
      cancer (CRC) survivors. METHODS: CRC survivors diagnosed between 2000 and 2009
      completed questionnaires in August 2013 (with self-reported weight, height, and
      self-assessed WC) and January 2014 (with HRQL using the EORTC-QLQ-C30). Clinical
      characteristics were retrieved from the Netherlands Cancer Registry. In
      multivariable linear regression analyses associations of BMI only, WC only and
      both BMI and WC with HRQL outcomes were assessed. RESULTS: 1,111 CRC survivors
      were included of whom 34% had a normal weight (18.5 <= BMI < 25 kg/m2), 49% had
      overweight (25 <= BMI < 30 kg/m2), 17% had obesity (BMI >= 30 kg/m2), and 44% had
      an increased WC (i.e., >102 and >88 cm for men and women, respectively). Both BMI
      and WC were separately associated with worse global health status, functioning,
      and more symptoms of fatigue. Increased WC was associated with lower physical,
      role and emotional functioning, regardless of BMI, with average differences
      ranging between 3 and 5 points. CONCLUSION: Future research on HRQL among CRC
      survivors should consider both BMI and WC. Furthermore, weight reduction trials
      should not only focus on general weight loss but also on the loss of abdominal
      fat.

PMID- 29035594
TI  - Total Body Water Dynamics Estimated with Bioelectrical Impedance Vector Analysis
      and B-Type Natriuretic Peptide After Exposure to Hypobaric Hypoxia: A Field
      Study.
AB  - Strapazzon, Giacomo, Matiram Pun, Tomas Dal Cappello, Emily Procter, Piergiorgio
      Lochner, Hermann Brugger, and Antonio Piccoli. Total body water dynamics
      estimated with bioelectrical impedance vector analysis and B-type natriuretic
      peptide after exposure to hypobaric hypoxia: A field study. High Alt Med Biol.
      18:384-391, 2017.-The relationship between total body water (TBW) dynamics and N
      terminal pro-B-type natriuretic peptide (NT-proBNP), a stable metabolite of B
      type natriuretic peptide, during acute high altitude exposure is not known. To
      investigate this, we transported 19 healthy lowland subjects to 3830 m with a
      helicopter after baseline measurements (262 m). The physiological measurements
      and clinical assessments were taken at 9, 24, 48, and 72 hours and on the eighth
      day of altitude exposure. A bioelectrical impedance vector analysis (BIVA) from
      height corrected Resistance-Reactance (R-Xc graph) was used to estimate TBW
      status. NT-proBNP was measured from venous blood samples. The changes in
      impedance vector were lengthened at 9 (p = 0.011), 48 (p = 0.033), and 72 hours
      (p = 0.015) indicating dehydration compared to baseline. However, there was no
      dehydration at 24 hours (p > 0.05) from the baseline and the subjects trended to
      get euhydrated from 9 to 24 hours (p = 0.097). The maximum percent changes in
      vector length from the baseline were within 10%-15%. There was a significant
      increase of natural logarithm (ln)(NT-proBNP) after ascent with a peak at 24
      hours, although similarly to BIVA values, ln(NT-proBNP) returned to baseline
      after 8 days of altitude exposure. The changes in impedance vector length were
      not correlated with the changes in ln(NT-proBNP) (r = -0.101, p = 0.656). In
      conclusion, the dehydration at high altitude as reflected by 10%-15% vector
      lengthening falls within "appropriate dehydration" in healthy lowland subjects.
      NT-proBNP does not simply reflect the TBW status during acute high altitude
      exposure and needs further investigation.

PMID- 29035595
TI  - The Influence of Physical Qualities on Activity Profiles of Female Australian
      Football Match Play.
AB  - PURPOSE: The transition of female Australian football (AF) players from amateur
      to semielite competitions has the potential for athletes to be underprepared for
      match play. To gain an understanding of the match demands of female football, the
      aims of this study were to highlight the physical qualities that discriminate
      selected and nonselected female AF players, investigate activity profiles of
      female AF players, and gain an understanding of the influence of physical
      qualities on performance in female AF Methods: Twenty-two female AF state academy
      players (mean [SD]: age = 23.2 [4.5] y) and 27 nonselected players (mean [SD]:
      age = 23.4 [4.9] y) completed a Yo-Yo intermittent recovery test level 1,
      countermovement jump, and 30-m sprint tests were completed prior to the
      competitive season. During 14 matches, players wore global positioning system
      units to describe the running demands of match play. RESULTS: Selected players
      were faster over 30 m (ES = 0.57; P = .04) and covered greater distances on the
      Yo-Yo IR1 (ES = 1.09; P < .001). Selected midfielders spent greater time on the
      field and covered greater total distances (ES = 0.73-0.85; P < .01). Players
      faster over 5 m (r = -.612) and 30 m (r = -.807) and who performed better on the
      Yo-Yo IR1 (r = .489) covered greater high-speed distances during match play.
      CONCLUSIONS: An emphasis should be placed on the development of physical fitness
      in this playing group to ensure optimal preparation for the national competition.

PMID- 29035596
TI  - The Elevated Track in Pole Vault: An Advantage During Run-Up?
AB  - BACKGROUND: Approach speed is a major determinant of pole-vault performance.
      Athletic jump events such as long jump, triple jump, and pole vault can utilize
      an elevated track for the runway. Feedback from athletes indicates a benefit of
      using an elevated track on their results. However, there is no evidence that
      elevated tracks increase athletes' performance. PURPOSE: To investigate the
      potential advantage of using an elevated track during elite pole-vault
      competitions on run-up speed parameters. METHODS: Performance and run-up criteria
      (speed, stride rate, contact, and aerial time) were measured from 20 high-level
      male pole-vaulters during official competitions on either a regular or an
      elevated track. Parameters comparisons were made between both conditions, and run
      up parameters were confronted to speed modification on the elevated track.
      RESULTS: Statistical analyses indicated that for the elevated track, there was a
      small improvement in final speed (1.1%), stride rate (1.1%), and takeoff distance
      (3.1%) and a small reduction in aerial time (-1.9%). The study highlighted
      different individual responses depending on athletes' capabilities. The authors
      noted that speed improvement was largely correlated with stride-rate improvement
      (r = .61) and contact-time reduction (r = -.51) for slower athletes. CONCLUSIONS:
      Elevated tracks can increase final approach speed in pole vault and positively
      influence performance. Interindividual responses were observed in these findings.

PMID- 29035597
TI  - Influence of 2-Weeks Ingestion of High Chlorogenic Acid Coffee on Mood State,
      Performance, and Postexercise Inflammation and Oxidative Stress: A Randomized,
      Placebo-Controlled Trial.
AB  - This study measured the influence of 2-weeks ingestion of high chlorogenic acid
      (CQA) coffee on postexercise inflammation and oxidative stress, with secondary
      outcomes including performance and mood state. Cyclists (N = 15) were randomized
      to CQA coffee or placebo (300 ml/day) for 2 weeks, participated in a 50-km
      cycling time trial, and then crossed over to the opposite condition with a 2-week
      washout period. Blood samples were collected pre- and postsupplementation, and
      immediately postexercise. CQA coffee was prepared using the Turkish method with
      30 g lightly roasted, highly ground Hambela coffee beans in 300 ml boiling water,
      and provided 1,066 mg CQA and 474 mg caffeine versus 187 mg CQA and 33 mg
      caffeine for placebo. Plasma caffeine was higher with CQA coffee versus placebo
      after 2-weeks (3.3-fold) and postexercise (21.0-fold) (interaction effect, p <
      .001). Higher ferric reducing ability of plasma (FRAP) levels were measured after
      exercise with CQA coffee versus placebo (p = .01). No differences between CQA
      coffee and placebo were found for postexercise increases in plasma IL-6 (p = .74)
      and hydroxyoctadecadienoic acids (9 + 13 HODEs) (p = .99). Total mood disturbance
      (TMD) scores were lower with CQA coffee versus placebo (p = .04). 50-km cycling
      time performance and power did not differ between trials, with heart rate and
      ventilation higher with CQA coffee, especially after 30 min. In summary, despite
      more favorable TMD scores with CQA coffee, these data do not support the chronic
      use of coffee highly concentrated with chlorogenic acids and caffeine in
      mitigating postexercise inflammation or oxidative stress or improving 50-km
      cycling performance.

PMID- 29035598
TI  - Rating of Perceived Exertion During Concentric and Eccentric Cycling: Are We
      Measuring Effort or Exertion?
AB  - : Despite the terms' often being used interchangeably, it has been suggested that
      perceptions of effort and perceptions of exertion may differ. Eccentric (ECC)
      cycling may provide a model of exercise by which differences between these
      perceptions can be examined. PURPOSE: To examine and compare perceptions of
      effort and exertion during ECC and concentric (CONC) cycling at 4 intensities.
      METHODS: Ten healthy male participants (mean [SD]: age = 29.8 [2.3] y) performed
      an incremental cycling test for the determination of maximal aerobic power
      output, followed in a randomized and crossover design, by four 5-min bouts (30%,
      60%, 80%, and maximal) of either ECC or CONC cycling. Through each bout,
      participants were asked to report their perceived effort, exertion, and muscle
      pain. Heart rate and oxygen consumption were continuously recorded throughout
      each bout. RESULTS: Perceived exertion was greater for CONC at 30% (8.5 [1.5] vs
      7.1 [1.8]; P = .01), 60% (12.4 [1.4] vs 10.3 [2.0]; P = .01), 80% (15.8 [1.7] vs
      12.4 [2.5]; P < .01), and maximal (17.2 [1.3] vs 15.6 [1.8]; P = .03) in
      comparison with ECC. Perceptions of effort and pain were similar between CONC and
      ECC. Heart rate and oxygen consumption were greater during CONC than ECC.
      CONCLUSIONS: Perceived exertion was greater during CONC compared with ECC
      cycling, yet effort was similar between conditions despite different
      physiological stress. Such findings have implications for understanding the
      development of such perceptions during exercise.

PMID- 29035599
TI  - Progressive Dehydration in Junior Laser Class Sailors During World Championship.
AB  - The purpose of this article is to assess the hydration status of elite young
      sailing athletes during World Championship competition. Twelve young, elite,
      male, Laser Class sailors (age: 15.8 +/- 1.1 y, height: 1.74 +/- 0.1 m, weight:
      65.1 +/- 1.5 kg, body fat: 12.5 +/- 3.1%, training experience: 7.0 +/- 1.2 y)
      participated in this descriptive study. After three-day baseline bodyweight
      measurements, hydration status was assessed via pre- and post-race body weights,
      urine-specific gravity, and thirst ratings via a visual analog scale during four
      consecutive days of racing. Measurements and data collection took place at the
      same time each racing day, with mean environmental temperature, humidity, and
      wind speed at 23.0 +/- 0.8 degrees C, 64-70%, and 9 +/- 1 knots, respectively.
      Average racing time was 130 +/- 9 min. Body weight was significantly decreased
      following each race-day as compared to prerace values (Day 1: -1.1 +/- 0.2, Day
      2: -2.5 +/- 0.1, Day 3: -2.8 +/- 0.1, and Day 4: -3.0 +/- 0.1% of body weight; p
      < 0.05). The participants exhibited dehydration of -2.9 +/- 0.2 and -5.8 +/- 0.2%
      of body weight before and after the fourth racing day as compared to the three
      day baseline body weight. Urine-specific gravity (pre-post -> Day 1: 1.014-1.017;
      Day 2: 1.019-1.024; Day 3: 1.021-1.026; Day 4: 1.022-1.027) and thirst (pre-post 
      > Day 1: 2.0-5.2; Day 2: 3.2-5.5; Day 3: 3.7-5.7; Day 4: 3.8-6.8) were also
      progressively and significantly elevated throughout the four days of competition.
      The data revealed progressive dehydration throughout four consecutive days of
      racing as indicated by decreased body weight, elevated urine concentration, and
      high thirst.

PMID- 29035600
TI  - Effect of the Pacing Strategies on the Open-Water 10-km World Swimming
      Championships Performances.
AB  - PURPOSE: To (1) compare the pacing strategies of different-level open-water
      swimmers during the 10-km race of the FINA 2015 Swimming World Championships and
      (2) relate these pacing strategies to the race performance. METHODS: Final and
      intermediate split times, as well as intermediate race positions, from the 10-km
      race participants (69 men and 51 women) were collected from the public domain and
      were divided into 5 groups (G1-G5) depending on their finishing positions.
      RESULTS: Medalists and finalists (G1 and G2, respectively) presented an even
      pacing profile with swimming velocities similar to those of the less successful
      swimmers (G3-G5) on the initial and middle stages of the race but a 1.5-3%
      increase in swimming velocity in the last quarter of the race. This acceleration
      toward the end of the race, or "end spurt," was largely related to the race
      performance and was not observed in the G3 and G4 (even-paced profile) or G5
      (positive pacing profile) groups. Intermediate race positions and lap rankings
      were negatively related to finishing position, indicating a delayed positioning
      of the most successful swimmers at 25%, 50%, and 75% of race distance.
      CONCLUSIONS: The adoption of a conservative starting strategy by open-water
      swimmers with a negative pacing profile and delayed partial positioning seems to
      increase the chances of overall race success, as it allows a fast end spurt that
      is closely related to successful finishing race positions.

PMID- 29035601
TI  - Skinfold Prediction Equations Fail to Provide an Accurate Estimate of Body
      Composition in Elite Rugby Union Athletes of Caucasian and Polynesian Ethnicity.
AB  - Body composition in elite rugby union athletes is routinely assessed using
      surface anthropometry, which can be utilized to provide estimates of absolute
      body composition using regression equations. This study aims to assess the
      ability of available skinfold equations to estimate body composition in elite
      rugby union athletes who have unique physique traits and divergent ethnicity. The
      development of sport-specific and ethnicity-sensitive equations was also pursued.
      Forty-three male international Australian rugby union athletes of Caucasian and
      Polynesian descent underwent surface anthropometry and dual-energy X-ray
      absorptiometry (DXA) assessment. Body fat percent (BF%) was estimated using five
      previously developed equations and compared to DXA measures. Novel sport and
      ethnicity-sensitive prediction equations were developed using forward selection
      multiple regression analysis. Existing skinfold equations provided unsatisfactory
      estimates of BF% in elite rugby union athletes, with all equations demonstrating
      a 95% prediction interval in excess of 5%. The equations tended to underestimate
      BF% at low levels of adiposity, whilst overestimating BF% at higher levels of
      adiposity, regardless of ethnicity. The novel equations created explained a
      similar amount of variance to those previously developed (Caucasians 75%,
      Polynesians 90%). The use of skinfold equations, including the created equations,
      cannot be supported to estimate absolute body composition. Until a population
      specific equation is established that can be validated to precisely estimate body
      composition, it is advocated to use a proven method, such as DXA, when absolute
      measures of lean and fat mass are desired, and raw anthropometry data routinely
      to derive an estimate of body composition change.

PMID- 29035602
TI  - Effect of Preexercise Ingestion of Modified Amylomaize Starch on Glycemic
      Response While Cycling.
AB  - Amylomaize-7 is classified as a resistant corn starch and is 68% digestible. When
      modified by partial hydrolysis in ethanol and hydrochloric acid its digestibility
      is 92%, yet retains its low glycemic and insulinemic properties. The purpose of
      this study was to characterize the metabolic response when modified amylomaize-7
      or dextrose is consumed in the hour before exercise, and to compare the effect on
      performance of a brief high-intensity cycling trial. Ten male, trained cyclists
      were given 1 g/kg body mass of dextrose (DEX) or modified amylomaize-7 (AMY-7) or
      a flavored water placebo (PL) 45 min prior to exercise on a cycle ergometer. A 15
      min ride at 60% Wmax was immediately followed by a self-paced time trial (TT)
      equivalent to 15 min at 80% Wmax. When cyclists consumed DEX, mean serum glucose
      concentration increased by 3.3 +/- 2.1 mmol/L before exercise, compared to stable
      serum glucose observed for AMY-7 or PL. Glucose concentrations returned to
      baseline by pre-TT in all treatments. However, the mean post-TT glucose
      concentration of the DEX group was significantly lower than baseline, AMY-7, or
      PL. Serum insulin concentration increased nine-fold from baseline to preexercise
      in the DEX trial, whereas PL or AMY-7 remained unchanged. Time required to
      complete the performance trial was not significantly different between DEX, AMY-7
      or PL. Preexercise ingestion of modified amylomaize-7 compared to dextrose
      resulted in a more stable serum glucose concentration, but did not offer a
      performance advantage in this high-intensity cycling trial.

PMID- 29035603
TI  - Competition Level Not Associated With Diet Quality in Marching Artists.
AB  - Marching artists are a unique group of athletes whose performance can be
      influenced by nutrition. Because physical demands are thought to be moderate to
      high, adequate energy and a variety of nutrient-dense foods are needed. The
      purpose of this study was to examine diet quality, physical activity, and eating
      behavior of marching artists across elite and nonelite competition levels. This
      cross-sectional analysis used the validated National Cancer Institute Diet
      History Questionnaire II, International Physical Activity Questionnaire, and
      Eating Behavior Patterns Questionnaire. Diet quality was assessed using the
      Healthy Eating Index (HEI) 2010. Marching artists who participated in marching
      band in 2015 were eligible. Those in Drum Corps International (DCI) were
      considered part of the elite level; all others were considered nonelite. Chi
      square analyses assessed associations between categorical variables and
      competition level, and independent sample t-tests assessed differences between
      continuous variables among competition level. Participants (n = 323) included 228
      (71%) DCI members and 95 (29%) non-DCI members who reported a mean age of 19.8 +/
      1.9 years. DCI members reported higher physical activity levels (p < 0.001) and
      fewer meal-skipping behaviors compared to non-DCI members (p < 0.001). The
      overall mean HEI score was 58.8 +/- 10.3, with no difference between competition
      levels. Only one participant overall (<1%) met the recommended intake level of
      whole grains. Additionally, 2% of participants met the sodium restriction
      recommendation and 7% met the empty calorie upper limit. Suboptimal diet quality
      combined with high levels of physical activity is a problem for marching artists
      that should be addressed through carefully planned interventions.

PMID- 29035604
TI  - Biomarkers for differentiation of patients with asthma and chronic obstructive
      pulmonary disease.
AB  - OBJECTIVE: Asthma and chronic obstructive pulmonary disease (COPD) are airflow
      limitation diseases with similar clinical manifestations but different
      pathophysiologic mechanisms. To implement the appropriate treatment, it is
      important to distinguish between asthma and COPD which sometimes might result
      difficult in clinical practice. We evaluated biomarkers to distinguish between
      asthma and COPD. METHODS: Blood eosinophil counts and fractional exhaled nitric
      oxide (FeNO) levels were analyzed. Serum periostin, interleukin-25 (IL-25), and
      immunoglobulin E (IgE) concentrations were compared between patients with asthma
      (n = 60), including atopic-asthma (n = 30) and non-atopic asthma (n = 30), and
      patients with COPD (n = 30). RESULTS: Significantly higher peripheral blood
      eosinophil counts (p < 0.001), FeNO levels (p < 0.001), and total serum IgE (P =
      0.003) concentrations, but not serum periostin (p = 0.584) or serum IL-25 (p =
      0.085) concentrations, were detected in patients with asthma compared to patients
      with COPD. Serum periostin and IgE concentrations were increased in patients with
      atopic-asthma compared with those with non-atopic asthma and COPD (p < 0.05). The
      FeNO levels were significantly correlated with the peripheral blood eosinophil
      counts (r = 0.430, p = 0.001) and serum IL-25 concentrations (r = 0.338, p =
      0.009) in patients with asthma. The serum periostin concentrations were also
      correlated with the serum IgE concentrations (r = 0.375, p = 0.003)and FeNO
      levels (r = 0.291, p = 0.024) in patients with asthma. Asthma patients were
      effectively differentiated from COPD patients based on the FeNO levels (p <
      0.001) and peripheral blood eosinophil counts (p < 0.001). CONCLUSIONS: FeNO
      levels and peripheral blood eosinophil counts were useful biomarkers for
      distinguishing between patients with asthma and COPD. Serum periostin and IgE
      concentrations could be biomarkers for atopic asthma.

PMID- 29035605
TI  - A two-staged approach to developing and evaluating an ontology for delivering
      personalized education to diabetic patients.
AB  - Ontologies are often used in biomedical and health domains to provide a concise
      and consistent means of attributing meaning to medical terminology. While they
      are novices in terms of ontology engineering, the evaluation of an ontology by
      domain specialists provides an opportunity to enhance its objectivity, accuracy,
      and coverage of the domain itself. This paper provides an evaluation of the
      viability of using ontology engineering novices to evaluate and enrich an
      ontology that can be used for personalized diabetic patient education. We
      describe a methodology for engaging healthcare and information technology
      specialists with a range of ontology engineering tasks. We used 87.8% of the data
      collected to validate the accuracy of our ontological model. The contributions
      also enabled a 16% increase in the class size and an 18% increase in object
      properties. Furthermore, we propose that ontology engineering novices can make
      valuable contributions to ontology development. Application-specific evaluation
      of the ontology using a semantic-web-based architecture is also discussed.

PMID- 29035606
TI  - Awareness, perception and barriers to seeking information from online academic
      databases and medical journals as sources of information.
AB  - Medical students' use of online medical journals as a source of information is
      crucial in the learning pathway to become medical doctors. We conducted a cross
      sectional survey study among University medical students between December 2012
      and March 2013 to assess their awareness, perceived usefulness, practices, and
      barriers to seeking information from online academic databases and medical
      journals. The response rate was 67.53%. The majority of the students knew of the
      availability of online academic databases and medical journals. The mean score
      for awareness (4.25 of possible 11.0), perceived usefulness (13.95 of possible
      33.0), and practice (10.67 of possible 33.0) were low. The mean barrier score
      toward using online academic databases and medical journals was 25.41 (of
      possible 45.0). Multivariate findings showed that significant barriers associated
      with overall usage of online databases and medical journals were 1) not knowing
      where or how to locate databases and 2) unsureness of using the Boolean
      operators. Availability of full text subscriptions was found to be an important
      factor in using online databases. Study findings highlighted the need to increase
      awareness of academic databases' availability and increase training on ways to
      search online academic databases and medical journals.

PMID- 29035607
TI  - Accuracy of W' Recovery Kinetics in High Performance Cyclists-Modeling
      Intermittent Work Capacity.
AB  - PURPOSE: With knowledge of an individual's critical power and W', the SKIBA 2
      model provides a framework with which to track W' balance during intermittent
      high-intensity work bouts. There are fears that the time constant controlling the
      recovery rate of W' (tauW') may require refinement to enable effective use in an
      elite population. METHODS: Four elite endurance cyclists completed an array of
      intermittent exercise protocols to volitional exhaustion. Each protocol lasted
      approximately 3.5-6 min and featured a range of recovery intensities, set in
      relation to the athlete's critical power (DCP). Using the framework of the SKIBA
      2 model, the tauW' values were modified for each protocol to achieve an accurate
      W' at volitional exhaustion. Modified tauW' values were compared with equivalent
      SKIBA 2 tauW' values to assess the difference in recovery rates for this
      population. Plotting modified tauW' values against DCP showed the adjusted
      relationship between work rate and recovery rate. RESULTS: Comparing modified
      tauW' values against the SKIBA 2 tauW' values showed a negative bias of 112 (46)
      s (mean +/- 95% confidence limits), suggesting that athletes recovered W' faster
      than predicted by SKIBA 2 (P = .0001). The modified tauW'-DCP relationship was
      best described by a power function: tauW' = 2287.2 * DCP-0.688 (R2 = .433).
      CONCLUSIONS: The current SKIBA 2 model is not appropriate for use in elite
      cyclists, as it underpredicts the recovery rate of W'. The modified tauW'
      equation presented will require validation but appears more appropriate for high
      performance athletes. Individual tauW' relationships may be necessary to maximize
      the model's validity.

PMID- 29035608
TI  - F508del CFTR gene mutation in patients with allergic bronchopulmonary
      aspergillosis.
AB  - OBJECTIVE: The F508del mutation occurs in approximately 3.5% of Caucasian
      population of Northern Europe. Heterozygotes have increased risk for asthma and
      reduced pulmonary function. Allergic bronchopulmonary aspergillosis (ABPA) is
      more common in patients with cystic fibrosis (CF). We aimed to establish the
      frequency of F508del mutation in adult patients with ABPA. METHODS: A
      retrospective matched case-control study of CF genotyped patients with ABPA seen
      at the National Aspergillosis Centre was undertaken. Key data were collected
      retrospectively from medical records, including respiratory comorbidities, total
      IgE, Aspergillus IgG and IgE, and immunoglobulins. Cystic fibrosis transmembrane
      regulator (CFTR) gene mutation analysis included multiplex PCR and sequencing.
      RESULTS: From a cohort of 189 ABPA patients, 156 were screened for common
      mutations and variants in the CFTR gene. Eighteen were heterozygous for at least
      one CFTR mutation; 12 (7.7%) were heterozygous for the F508del, notably; 3 were
      heterozygous for the intron 8 5T variant; and 1 for an intronic variant of
      uncertain significance, c.3139 + 18C>T. Eight (67%) had asthma, 7 (58%) had CT
      defined bronchiectasis, 4 (33%) hypergammaglobulinemia (>16 g/L), 3 (25%)
      sinusitis and 1 (8%) chronic pulmonary aspergillosis. Eight (67%) had elevated
      Aspergillus IgG antibodies (42-98 mg/L), and 8 (67%) had total IgE above 1,000
      KIU/L. Two individuals heterozygous for the F508del mutation and the TG12T5
      variant were diagnosed with CF, leading to a de novo CF discovery rate of 1.3%.
      CONCLUSIONS: In our ABPA patient cohort, the presence of the delta F508 mutation
      was higher than that seen in general population. Genetic counseling for CFTR
      genotyping might be appropriate for these patients.

PMID- 29035609
TI  - Single-Surgeon Experience and Complications of a Fixed-Bearing Total Ankle
      Arthroplasty.
AB  - BACKGROUND: Total ankle arthroplasty (TAA) has historically resulted in inferior
      survivorship rates compared with total hip and knee arthroplasty, because of
      technical issues unique to ankle anatomy. In this study, a single-surgeon series
      of intra- and postoperative complications as well as resultant
      reoperations/revisions of the Tornier Salto Talaris, a fixed-bearing TAA
      prosthesis, were reviewed. METHODS: Medical records from index procedure to
      latest follow-up of primary TAA were reviewed. Complications were categorized
      according to the Glazebrook classification; additional complications were
      documented. Concurrent procedures were recorded, and radiographs were analyzed
      for alignment, subsidence, and cyst formation. Time to complication onset and
      learning curve analyses were performed. One hundred four Salto Talaris TAA
      prostheses (96 patients), with an average follow-up of 46 months, were included.
      RESULTS: Thirty-five complications were identified in 32 ankles with a 34%
      complication rate, resulting in 11 reoperations (5 TAA revisions). Technical
      error (n = 12), wound healing (n = 9), and aseptic loosening (n = 4) were the
      most common complications, and there were no statistically significant
      differences in demographics or follow-up duration between cases with versus
      without complications. In both the cohorts with and without complications, there
      were moderate, negative correlations between radiographically observed keel
      osteopenia and lucency (rho = -0.548, P = .00125, and rho = -0.416, P = .000303,
      respectively); also, in the complication cohort, a weak, positive correlation
      between subsidence and lucency (rho = 0.357, P = .0450) was found. CONCLUSION:
      Salto Talaris TAA survivorship and reoperation rates in our series were
      comparable with previous reports, using either the same or similar mobile-bearing
      prostheses; new information regarding complication, radiographic, and learning
      curve analyses was presented. LEVEL OF EVIDENCE: Level IV, retrospective case
      series.

PMID- 29035610
TI  - Critical assessment of health disparities across subpopulation groups through a
      social determinants of health perspective: The case of type 2 diabetes patients.
AB  - BACKGROUND: Studies on diabetes have shown that population subgroups have varying
      rates of medical events and related procedures; however, existing studies have
      investigated either medical events or procedures, and hence, it is unknown
      whether disparities exist between medical events and procedures. PURPOSE: The
      objective of this study is to investigate how diabetes-related medical events and
      procedures are different across population subgroups through a social
      determinants of health (SDH) perspective. METHODS: Because the purpose of this
      manuscript is to explore whether statistically significant health disparities
      exist across population subgroups regarding diabetes patients' medical events and
      procedures, group difference test methods were employed. Diabetes patients' data
      were drawn from the Cerner Health Facts(r) data warehouse. RESULTS: The study
      revealed systematic disparities across population subgroups regarding medical
      events and procedures. The most significant disparities were connected with
      smoking status, alcohol use, type of insurance, age, marital status, and gender.
      CONCLUSIONS: Some population subgroups have higher rates of medical events and
      yet receive lower rates of treatments, and such disparities are systematic.
      Socially constructed behaviors and structurally discriminating public policies in
      part contribute to such systematic health disparities across population
      subgroups.

PMID- 29035611
TI  - Are People Who Inject Drugs Frequent Users of Emergency Department Services? A
      Cohort Study (2008-2013).
AB  - BACKGROUND: Although people who inject drugs (PWID) have been described as
      frequent users of emergency services, the majority of research is cross-sectional
      and involves records from a single emergency department (ED). OBJECTIVES: We
      describe characteristics of state-wide ED presentations in a cohort of PWID, and
      compare presentation rates to the general population. We also examine
      characteristics associated with frequent ED use. METHODS: We used data from a
      retrospective linkage of public ED presentations from a cohort of 678 PWID
      between January 2008 and June 2013. Common principal diagnoses were described
      using the International Classification of Diseases, Tenth Revision, Australian
      Modification (ICD-10-AM) chapter headings. The ED presentation trend was
      estimated using negative-binomial regression. Characteristics associated with
      frequent use of EDs were identified using generalized estimating equations
      (GEEs). RESULTS: There were 3437 presentations over 4163.5 person-years (PY) and
      the most common principal diagnosis was injury, poisoning and other externalities
      (19%). ED presentations increased by 4% every six months (95% confidence interval
      (CI) 0.1%-0.8%) and were three times greater than the general population. A
      quarter (24%) of the cohort presented frequently, and they were more likely to
      have noninjury-related diagnoses and be aged below 30 years, and less likely to
      have nonurgent presentations and be male. CONCLUSIONS: PWID use EDs at a higher
      rate than the general population, and typically present with injuries and mental
      and behavioral disorders. Referrals to drug treatment, mental health, and social
      support services can improve patient care and reduce the burden on EDs.

PMID- 29035612
TI  - Enhanced Vitreous Imaging in Uveitis.
AB  - PURPOSE: To study the structural visibility of the posterior vitreous cavity and
      vitreoretinal interface using Spectral Domain-Optical Coherence Tomography in
      patients with uveitis using conventional, Enhanced Depth Imaging (EDI), Combined
      Depth Imaging (CDI), and Enhanced Vitreous Imaging (EVI) techniques. METHODS: It
      was an observational cross-sectional study of 59 eyes of 33 patients between age
      group 12-72 years (Median 43) diagnosed as uveitis with posterior segment
      manifestations underwent OCT using conventional, EDI, CDI, and EVI techniques.
      The visibility of posterior vitreous was graded in all the techniques. RESULTS: A
      statistically significant difference was seen in posterior vitreous visibility on
      comparing all four techniques. EVI showed better visibility of posterior vitreous
      cavity compared to all other techniques (P < 0.001). CONCLUSIONS: EVI technique
      provides better structural visibility of posterior vitreous compared to
      conventional, EDI, and CDI techniques.

PMID- 29035613
TI  - Quercetin-Induced AMP-Activated Protein Kinase Activation Attenuates
      Vasoconstriction Through LKB1-AMPK Signaling Pathway.
AB  - The vascular tone plays an important role in blood pressure and flow. It is
      influenced by the contraction of vascular smooth muscle cells (VSMCs), which in
      turn is regulated by the balance between the myosin light chain kinase (MLCK) and
      the phosphorylated myosin light chain (p-MLC). Quercetin is a common flavonoid
      which is found in many fruits and red wine. Although quercetin has been widely
      reported to be involved in cell proliferation, migration, and apoptosis in VSMCs,
      it has not yet been demonstrated whether quercetin is related to vasocontraction,
      a function regulated by the AMP-activated protein kinase (AMPK) signaling
      pathway. Accordingly, the aim of this study is to investigate the molecular
      mechanism through which the quercetin-activated LKB1-AMPK signaling pathway
      regulates the contraction of VSMCs. In cultured VSMCs, quercetin activated AMPK
      in a dose- and time-dependent manner. Quercetin inhibited the phenylephrine (PE)
      induced expression of MLCK and p-MLC through the LKB1-AMPK signaling pathway and
      decreased the mRNA level of MLCK. Adenovirus-AMPK DN alpha1 and AMPK DN alpha2
      transduced VSMCs displayed higher p-MLC expression. Moreover, quercetin inhibited
      the PE-mediated contraction in rat aorta. These data suggest that the quercetin
      activated LKB1-AMPK signaling pathway regulates VSMC contraction by inhibiting
      MLCK and p-MLC; hence, it may be a therapeutic intervention for the treatment of
      cardiovascular disorders such as atherosclerosis and hypertension.

PMID- 29035615
TI  - Improving Mobility Performance in Wheelchair Basketball.
AB  - OBJECTIVE: This study aimed to investigate which characteristics of athlete,
      wheelchair and athlete-wheelchair interface are the best predictors of wheelchair
      basketball mobility performance. DESIGN: A total of 60 experienced wheelchair
      basketball players performed a wheelchair mobility performance test to assess
      their mobility performance. To determine which variables were the best predictors
      of mobility performance, forward stepwise linear regression analyses were
      performed on a set of 33 characteristics, including 10 athlete, 19 wheelchair,
      and 4 athlete-wheelchair interface characteristics. RESULTS: A total of 8 of the
      characteristics turned out to be significant predictors of wheelchair basketball
      mobility performance. Classification, experience, maximal isometric force, wheel
      axis height, and hand rim diameter-which both are interchangeable with each other
      and wheel diameter-camber angle, and the vertical distance between shoulder and
      rear wheel axis-which was interchangeable with seat height-were positively
      associated with mobility performance. The vertical distance between the front
      seat and the footrest was negatively associated with mobility performance.
      CONCLUSION: With this insight, coaches and biomechanical specialists are provided
      with statistical findings to determine which characteristics they could focus on
      best to improve mobility performance. Six out of 8 predictors are modifiable and
      can be optimized to improve mobility performance. These adjustments could be
      carried out both in training (maximal isometric force) and in wheelchair
      configurations (eg, camber angle).

PMID- 29035614
TI  - The Impact and Implication of Peripheral Vascular Leakage on Ultra-Widefield
      Fluorescein Angiography in Uveitis.
AB  - PURPOSE: To study if peripheral vascular leakage (PVL) on ultra-widefield
      fluorescein angiography (UWFFA) prognosticates complications of uveitis or
      necessitates treatment augmentation. METHODS: Retrospective cohort study of
      uveitis patients imaged with UWFFA and >=1 yr of follow-up. RESULTS: We included
      73 eyes of 42 patients with uveitis. There was no difference in baseline,
      intermediate, final visual acuity (p = 0.47-0.95) or rates of cystoid macular
      edema (CME) (p = 0.37-0.87) in eyes with PVL vs. those without. Eyes with PVL
      receiving baseline treatment augmentation were more likely to have baseline CME
      but were not more likely to have impaired visual acuity at final follow-up. PVL
      was independently associated with treatment augmentation on generalized
      estimating equation analysis with multivariable linear regression (OR: 4.39, p =
      0.015). CONCLUSIONS: PVL did not confer an increased risk of impaired VA or CME
      at >=1 yr follow-up but was possibly an independent driver of treatment
      augmentation.

PMID- 29035616
TI  - Role of Kindness in Cancer Care.
AB  - The wonders of high-tech cancer care are best complemented by the humanity of
      high-touch care. Simple kindnesses can help to diffuse negative emotions that are
      associated with cancer diagnosis and treatment-and may even help to improve
      patients' outcomes. On the basis of our experience in cancer care and research,
      we propose six types of kindness in cancer care: deep listening , whereby
      clinicians take the time to truly understand the needs and concerns of patients
      and their families; empathy for the patient with cancer, expressed by both
      individual clinicians and the care culture, that seeks to prevent avoidable
      suffering; generous acts of discretionary effort that go beyond what patients and
      families expect from a care team; timely care that is delivered by using a
      variety of tools and systems that reduce stress and anxiety; gentle honesty,
      whereby the truth is conveyed directly in well-chosen, guiding words; and support
      for family caregivers, whose physical and mental well-being are vital components
      of the care their loved ones receive. These mutually reinforcing manifestations
      of kindness-exhibited by self-aware clinicians who understand that how care is
      delivered matters-constitute a powerful and practical way to temper the emotional
      turmoil of cancer for patients, their families, and clinicians themselves.

PMID- 29035617
TI  - Role of Bone-Modifying Agents in Metastatic Breast Cancer: An American Society of
      Clinical Oncology-Cancer Care Ontario Focused Guideline Update Summary.

PMID- 29035618
TI  - Impact of Intensity-Modulated Radiotherapy on Health Care Costs of Patients With
      Anal Squamous Cell Carcinoma.
AB  - PURPOSE: Drivers of variation in the cost of care after chemoradiotherapy for the
      management of anal squamous cell carcinoma (SCC) have not been fully elucidated.
      We sought to characterize the direct and indirect impact of radiotherapy modality
      on health care costs among patients with anal SCC. PATIENTS AND METHODS: A
      retrospective cohort study was performed using the 2014 linkage of the SEER
      Medicare database. We identified 1,025 patients with anal SCC diagnosed between
      2001 and 2011 and treated with chemoradiotherapy. Propensity score matching was
      used to balance baseline differences between patients treated with intensity
      modulated radiotherapy (IMRT) and those treated with three-dimensional conformal
      radiotherapy (3D-CRT). Differences in total, cancer-attributable, and procedure
      specific costs between groups were measured. RESULTS: Radiation-related, patient
      out-of-pocket, and total costs in the 1-year period after radiotherapy start were
      all higher for the IMRT group than the 3D-CRT group (median total cost, $35,890 v
      $27,262, respectively; P < .001). Patients who received IMRT had lower cumulative
      costs associated with urgent hospitalizations and emergency department visits at
      both 9 months and 1 year after treatment start compared with a matched cohort of
      patients who received 3D-CRT (median, $711 v $4,957 at 1 year, respectively; P =
      .021). CONCLUSION: Although total costs of care were higher for IMRT compared
      with 3D-CRT, primarily as a result of higher radiotherapy-specific costs, IMRT
      was associated with decreased unplanned health care utilization costs starting at
      9 months after treatment start. Radiotherapy-centered episodes of care may need
      to encompass a longer time horizon to capture the full cost savings associated
      with more advanced radiation modalities.

PMID- 29035620
TI  - Effectiveness of Salted Ice Bag Versus Cryocompression on Decreasing
      Intramuscular and Skin Temperature.
AB  - CONTEXT: Rest, ice, compression, and elevation are commonly recommended
      immediately after injury. Traditionally, ice bag (IB) with elastic wrap
      compression has been utilized; however, recently intermittent cryocompression
      units are being used. Limited research has evaluated tissue temperature decreases
      with intermittent cryocompression units. OBJECTIVE: Evaluate magnitude of muscle
      and skin cooling. DESIGN: Repeated-measures counterbalanced study. SETTING:
      University research laboratory. PATIENTS OR OTHER PARTICIPANTS: Twelve healthy
      college-aged participants (4 males and 8 females; age = 23.08 [1.93] y; height =
      171.66 [9.47] cm; mass = 73.67 [13.46] kg; subcutaneous thickness = 0.90 [0.35]
      cm) without compromised circulation or injury. INTERVENTION(S): Salted IB,
      GameReady (GR), and PowerPlay-ice bag (PP-ice) were applied to the posterior
      aspect of the nondominant calf for 30 minutes; participants underwent each
      treatment in counterbalanced order. MAIN OUTCOME MEASURE(S): Muscle temperature
      measured via 21-gauge catheter thermocouple; skin temperature measured via a
      surface thermocouple. Temperatures were recorded at baseline and during a 30
      minute treatment. Correlations were evaluated between muscle and skin
      temperatures. RESULTS: Nonsignificant treatment * time interaction and
      nonsignificant main effect of treatment for intramuscular cooling. Mean Decrease
      From Baseline: IB, 6.4 degrees C (+/-2.8); GR, 5.4 degrees C (+/-1.1); PP-ice,
      4.8 degrees C (+/-2.8). Nonsignificant treatment * time interaction for skin
      cooling (F20,200 = 1.440, P = .65, [Formula: see text], and observed beta =
      0.773), but significant main effect for treatment (F10,100 = 5.279, P = .03,
      [Formula: see text], and observed beta = 1.00). Mean Decrease From Baseline: IB,
      17.0 degrees C; GR, 16.4 degrees C; PP-ice, 14.6 degrees C. No significant
      correlation between intramuscular and skin temperatures in any condition at any
      time point. No significant correlation between adipose tissue thickness and
      maximum temperature decrease with any modality. CONCLUSIONS: Salted IB with
      elastic wrap compression, GR, and PP-ice produced equivalent intramuscular
      temperature decreases during the treatment period.

PMID- 29035619
TI  - Personalized medicine with biologics for severe type 2 asthma: current status and
      future prospects.
AB  - Asthma affects more than 300 million people worldwide and poses a large
      socioeconomic burden, particularly in the 5% to 10% of severe asthmatics. So far,
      each entry of new biologics in clinical trials has led to high expectations for
      treating all severe asthma forms, but the outcome has only been successful if the
      biologic, as add-on treatment, targeted specific patient subgroups. Indeed, we
      now realize that asthma is a heterogeneous disease with multiple phenotypes,
      based on distinct pathophysiological mechanisms, called endotypes. Thus, asthma
      therapy is gradually moving to a personalized medicine approach, tailored to
      individual's asthma endotypes identified through biomarkers. Here, we review the
      clinical efficacy of antibody-related therapeutics undergoing clinical trials, or
      those already approved, for the treatment of severe type 2 asthma. Biologics
      targeting type 2 cytokines have shown consistent efficacy, especially in patients
      with evidence of type 2 inflammation, suggesting that the future of asthma
      biologics is promising.

PMID- 29035621
TI  - Relationship Between Muscle Strength Asymmetry and Body Sway in Older Adults.
AB  - The purpose of this study was to investigate the relationship between muscle
      strength asymmetry and body sway while walking. We studied 63 older adult women.
      Strong side and weak side of knee extension strength, toe grip strength, hand
      grip strength, and body sway while walking were measured. The relationship
      between muscle strength asymmetry for each muscle and body sway while walking was
      evaluated using Pearson's correlation coefficient. Regarding the muscles
      recognized to have significant correlation with body sway, the asymmetry cutoff
      value causing an increased sway was calculated. Toe grip strength asymmetry was
      significantly correlated with body sway. Toe grip strength asymmetry causing an
      increased body sway had a cutoff value of 23.5%. Our findings suggest toe grip
      strength asymmetry may be a target for improving gait stability.

PMID- 29035622
TI  - Health Insurance and the Promise of Incrementalism.

PMID- 29035623
TI  - The Impact of Knee Injury History on Health-Related Quality of Life in Adolescent
      Athletes.
AB  - CONTEXT: Current evidence suggests that, despite returning to full participation,
      physically active adults with a previous knee injury experience lower health
      related quality of life (HRQOL) than those with no knee injury history. It is
      unknown if this relationship is present in adolescent athletes. OBJECTIVE: To
      determine the impact of knee injury history on HRQOL in adolescent athletes who
      were medically cleared for full participation. DESIGN: Cross-sectional. SETTING:
      Athletic training clinics. PARTICIPANTS: A convenience sample of 183 adolescent
      athletes, who were medically cleared for full participation, were grouped by self
      report of a previous knee injury: positive knee injury history (HIS; n = 36, age
      = 15.7 [1.4] y, height = 168.0 [11.9] cm, and weight = 71.8 [11.9] kg) and no
      knee injury history (NO-HIS; n = 147, age = 15.5 [1.4] y, height = 166.0 [10.5]
      cm, and weight = 67.6 [14.6] kg). INTERVENTIONS: Participants completed the
      Pediatric International Knee Documentation Committee form and Pediatric Quality
      of Life Inventory during their preparticipation examination. MAIN OUTCOME
      MEASURES: Generalized linear models were used to compare group differences for
      the total and subscale scores of the Pediatric International Knee Documentation
      Committee and Pediatric Quality of Life Inventory. RESULTS: Main effects of
      injury group indicated that the HIS group reported significantly lower scores
      than the NO-HIS group for the Pediatric International Knee Documentation
      Committee total score (P < .001; HIS = 79.2 [21.7], NO-HIS = 95.8 [8.6]) and for
      the Pediatric Quality of Life Inventory total (P = .001; HIS = 85.7 [10.9], NO
      HIS = 90.9 [7.3]), physical functioning (P = .002; HIS = 86.7 [13.6], NO-HIS =
      92.1 [8.2]), school functioning (P = .01; HIS = 80.6 [12.4], NO-HIS = 86.8
      [12.2]), and social functioning (P = .01; HIS = 89.3 [12.4], NO-HIS = 94.6 [8.9])
      scores. No group differences were reported for the emotional functioning subscale
      (P = .13; HIS = 85.7 [17.7], NO-HIS = 89.7 [13.1]). No interactions or main
      effects of sex were reported (P > .05). CONCLUSIONS: Our findings suggest that,
      despite returning to full sport participation, adolescent athletes with a
      previous knee injury generally experience lower HRQOL than their peers with no
      knee injury history, specifically for knee-specific HRQOL, physical functioning,
      school functioning, and social functioning. Our results are similar to previous
      findings reported in college athletes and military cadets.

PMID- 29035624
TI  - Nurses' perceptions and problems in the usability of a medication safety app.
AB  - INTRODUCTION: The majority of medication apps support medication adherence.
      Equally, if not more important, is medication safety. Few apps report on
      medication safety, and fewer studies have been conducted with these apps.
      OBJECTIVES: The usability of a medication safety app was tested with nurses to
      reveal their perceptions of the graphical user interface and to discover problems
      they encountered in using the app. METHODS: Usability testing of the app was
      conducted with RN-BSN students and informatics students (n = 18). Perceptions of
      the graphical components were gathered in pretest and posttest questionnaires,
      and video recordings of the usability testing were transcribed. The significance
      of the difference in mean performance time for 8 tasks was tested, and
      qualitative analysis was deployed to identify problems encountered and to rate
      the severity of each problem. RESULTS: While all participants perceived the
      graphical user interface as easy to understand, nurses took significantly more
      time to complete certain tasks. More nurses found the medication app to be
      lacking in intuitiveness of user interface design, in capability to match real
      world data, and in providing optimal information architecture. CONCLUSION: To
      successfully integrate mobile devices in healthcare, developers must address the
      problems that nurses encountered in use of the app.

PMID- 29035625
TI  - Chickens with humanized immunoglobulin genes generate antibodies with high
      affinity and broad epitope coverage to conserved targets.
AB  - Transgenic animal platforms for the discovery of human monoclonal antibodies have
      been developed in mice, rats, rabbits and cows. The immune response to human
      proteins is limited in these animals by their tolerance to mammalian-conserved
      epitopes. To expand the range of epitopes that are accessible, we have chosen an
      animal host that is less phylogenetically related to humans. Specifically, we
      generated transgenic chickens expressing antibodies from immunoglobulin heavy and
      light chain loci containing human variable regions and chicken constant regions.
      From these birds, paired human light and heavy chain variable regions are
      recovered and cloned as fully human recombinant antibodies. The human antibody
      expressing chickens exhibit normal B cell development and raise immune responses
      to conserved human proteins that are not immunogenic in mice. Fully human
      monoclonal antibodies can be recovered with sub-nanomolar affinities. Binning
      data of antibodies to a human protein show epitope coverage similar to wild type
      chickens, which we previously showed is broader than that produced from rodent
      immunizations.

PMID- 29035626
TI  - Performance evaluation of poly-urethane foam packed-bed chemical scrubber for the
      oxidative absorption of NH3 and H2S gases.
AB  - The feasibility of open-pore polyurethane (PU) foam as packing material for wet
      chemical scrubber was tested for NH3 and H2S removals. The foam is inexpensive,
      light-weight, highly porous (low pressure drop) and provides large surface area
      per unit volume, which are desirable properties for enhanced gas/liquid mass
      transfer. Conventional HCl/HOCl (for NH3) and NaOH/NaOCl (for H2S) scrubbing
      solutions were used to absorb and oxidize the gases. Assessment of the wet
      chemical scrubbers reveals that pH and ORP levels are important to maintain the
      gas removal efficiencies >95%. A higher re-circulation rate of scrubbing
      solutions also proved to enhance the performance of the NH3 and H2S columns.
      Accumulation of salts was confirmed by the gradual increase in total dissolved
      solids and conductivity values of scrubbing solutions. The critical elimination
      capacities at >95% gas removals were found to be 5.24 g NH3-N/m3-h and 17.2 g H2S
      S/m3-h at an empty bed gas residence time of 23.6 s. Negligible pressure drops (<
      4 mm H2O) after continuous operation demonstrate the suitability of PU as a
      practical packing material in wet chemical scrubbers for NH3 and H2S removals
      from high-volume dilute emissions.

PMID- 29035627
TI  - METALLOTHIONEIN genes encoding ROS scavenging enzymes are down-regulated in the
      root cortex during inducible aerenchyma formation in rice.
AB  - Under waterlogged conditions, roots of gramineous plants form lysigenous
      aerenchyma (internal gas spaces) by inducing the death of cortical cells. Rice
      (Oryza sativa) roots induce aerenchyma formation through ethylene- and reactive
      oxygen species (ROS)-mediated signaling. Metallothionein (MT) is a small,
      cysteine-rich protein that acts as a ROS scavenger. In rice roots, the expression
      of MT1a, MT1b, MT1c and MT1Ld were higher than those of the other MT genes. In
      the root cortex, where aerenchyma forms exclusively, the expression of MT1a, MT1b
      and MT1Ld was reduced prior to aerenchyma formation. These findings suggest that
      ROS accumulation in the cortex, which is aided by downregulation of MT1 genes, is
      needed for aerenchyma formation in rice roots.

PMID- 29035628
TI  - Effects of nitrate and sulfate on the performance and bacterial community
      structure of membrane-less single-chamber air-cathode microbial fuel cells.
AB  - Membrane-less, single-chamber, air-cathode, microbial fuel cells (ML-SC MFCs)
      have attracted attention as being suitable for wastewater treatment. In this
      study, the effects of nitrate and sulfate on the performance of ML-SC MFCs and
      their bacterial structures were evaluated. The maximum power density increased
      after nitrate addition from 8.6 mW.m-2 to 14.0 mW.m-2, while it decreased after
      sulfate addition from 11.5 mW.m-2 to 7.7 mW.m-2. The chemical oxygen demand
      removal efficiencies remained at more than 90% regardless of the nitrate or
      sulfate additions. The nitrate was removed completely (93.0%) in the ML-SC MFC,
      while the sulfate removal efficiency was relatively low (17.6%). Clostridium
      (23.1%), Petrimonas (20.0%), and unclassified Rhodocyclaceae (6.2%) were dominant
      on the anode before the addition of nitrate or sulfate. After the addition of
      nitrate, Clostridium was still the most dominant on the anode (23.6%), but
      Petrimonas significantly decreased (6.0%) and unclassified Rhodocyclaceae
      increased (17.1%). After the addition of sulfate, the amount of Clostridium
      almost doubled in the composition on the anode (43.2%), while Petrimonas
      decreased (5.5%). The bacterial community on the cathode was similar to that on
      the anode after the addition of nitrate. However, Desulfovibrio was remarkably
      dominant on the cathode (32.9%) after the addition of sulfate. These results
      promote a deeper understanding of the effects of nitrate or sulfate on the ML-SC
      MFCs' performance and their bacterial community.

PMID- 29035630
TI  - A Population Health Measurement Framework: Evidence-Based Metrics for Assessing
      Community-Level Population Health in the Global Budget Context.
AB  - Population health is one of the pillars of the Triple Aim to improve US health
      care. The authors developed a framework for population health measurement and a
      proposed set of measures for further exploration to guide the population health
      efforts in Maryland. The authors searched peer-reviewed, expert-authored
      literature and current public health measures. Using a semi-structured analysis,
      a framework was proposed, which consisted of a conceptual model of several
      domains and identified population health measures addressing them. Stakeholders
      were convened to review the framework and identified the most feasible population
      health measures considering the underlying health information technology (IT)
      infrastructure in Maryland. The framework was organized based on health system
      factors, determinants of health, and population-based and clinical outcomes.
      Measurement specifications were developed that addressed different aspects of
      selected measures and assessed various national and local data sources for
      selected measures. Data sources were identified based on their key
      characteristics, challenges, opportunities, and potential applicability to the
      proposed measures, as well as the issue of interoperability of data sources among
      different organizations. The proposed framework and measures can act as a
      platform to quantify the determinants of health and the state overall population
      health goals. Key considerations for developing a population health measures
      framework include health IT infrastructure, data denominators, feasibility,
      health system environment, and policy factors. Measurement development and
      progression using the framework will largely depend on the users' focus areas and
      availability of data. The authors believe that the proposed framework and road
      map can serve as a model for communities elsewhere.

PMID- 29035632
TI  - A multiobjective optimization model and an orthogonal design-based hybrid
      heuristic algorithm for regional urban mining management problems.
AB  - : In this paper, a multiobjective mixed-integer piecewise nonlinear programming
      model (MOMIPNLP) is built to formulate the management problem of urban mining
      system, where the decision variables are associated with buy-back pricing,
      choices of sites, transportation planning, and adjustment of production capacity.
      Different from the existing approaches, the social negative effect, generated
      from structural optimization of the recycling system, is minimized in our model,
      as well as the total recycling profit and utility from environmental improvement
      are jointly maximized. For solving the problem, the MOMIPNLP model is first
      transformed into an ordinary mixed-integer nonlinear programming model by
      variable substitution such that the piecewise feature of the model is removed.
      Then, based on technique of orthogonal design, a hybrid heuristic algorithm is
      developed to find an approximate Pareto-optimal solution, where genetic algorithm
      is used to optimize the structure of search neighborhood, and both local
      branching algorithm and relaxation-induced neighborhood search algorithm are
      employed to cut the searching branches and reduce the number of variables in each
      branch. Numerical experiments indicate that this algorithm spends less CPU
      (central processing unit) time in solving large-scale regional urban mining
      management problems, especially in comparison with the similar ones available in
      literature. By case study and sensitivity analysis, a number of practical
      managerial implications are revealed from the model. IMPLICATIONS: Since the
      metal stocks in society are reliable overground mineral sources, urban mining has
      been paid great attention as emerging strategic resources in an era of resource
      shortage. By mathematical modeling and development of efficient algorithms, this
      paper provides decision makers with useful suggestions on the optimal design of
      recycling system in urban mining. For example, this paper can answer how to
      encourage enterprises to join the recycling activities by government's support
      and subsidies, whether the existing recycling system can meet the developmental
      requirements or not, and what is a reasonable adjustment of production capacity.

PMID- 29035631
TI  - Bioconcentration and half-life of quinalphos pesticide in rice-fish integration
      system in the Mekong Delta, Vietnam.
AB  - In order to determine the distribution and enable the elimination of quinalphos,
      a popular active pesticide compound used in the Mekong Delta, an experiment was
      set up in a rice-fish integration system in Can Tho City, Vietnam. Fish was
      stocked into the field when the rice was two-months old. Quinalphos was applied
      twice in doses of 42.5 g per 1000 m2. Water, fish and sediment samples were
      collected at time intervals and analyzed by a Gas Chromatography Electron Capture
      Detector system. The results show that quinalphos residues in fish muscles were
      much higher than those of the water and the bioconcentration factor (logBCF) was
      above 2 for the fish. The half-life of first and second quinalphos applications
      were 12.2 and 11.1 days for sediment, 2.5 and 1.1 days for silver barb, 1.9 and
      1.3 days for common carp, and 1.1 and 1.0 days for water, respectively.

PMID- 29035633
TI  - The effect of technology assisted therapy for intellectually and visually
      impaired adults suffering from separation anxiety: Conquering the fear.
AB  - Persons with an intellectual disability (ID) are at risk of developing separation
      anxiety (SA) and, if left untreated, this can be a risk factor for the
      development of psychopathology. The effects of an intervention, namely technology
      assisted therapy for SA (TTSA), were examined on the SA, challenging behavior,
      psychosocial functioning, and quality of life (QOL) experienced by moderate to
      mild intellectually and visually disabled adults. This study aimed to determine
      whether TTSA reduces SA and challenging behavior in persons with ID and visual
      impairment, and if this results in increased psychosocial functioning and QOL. A
      pre-experimental within-group design with randomized multiple baselines and
      staggered intervention start-points was used (n = 6). The variables were
      monitored with standardized instruments. The frequencies of each participant's
      use of the technology and the frequency and intensity of their behavior were
      recorded over time. Results indicate that the SA and challenging behavior
      experienced by the participants decreased significantly and their psychosocial
      functioning and QOL increased significantly. The conclusions are that TTSA has
      the potential to be a valid intervention to address SA in adults with visual and
      moderate to mild IDs.

PMID- 29035634
TI  - Phthalides as promising insecticides against Tuta absoluta (Lepidoptera:
      Gelechiidae).
AB  - In this study, the insecticide potential of eight phthalides derived from furan
      2(5H)-one was evaluated against Tuta absoluta (Meyrick) (Lepidoptera:
      Gelechiidae) larvae. The potency of the most active phthalides and the
      susceptibility of six different T. absoluta populations to these compounds were
      determined. The toxicity of these molecules to two non-target species (Solenopsis
      saevissima Smith and Tetragonisca angustula Latreille) was also evaluated. Two
      phthalides (3 and 4) presented insecticide potential against T. absoluta.
      Phthalide 4 was as toxic as piperine (positive control) and both phthalides
      exhibited rapid action (LT50 < 2 hours). The variation in the susceptibility of
      T. absoluta populations to the phthalides 3 and 4 was low. Neither phthalide
      presented physiological selectivity for non-target species. Therefore, the
      phthalides 3 and 4 are promising molecules, or at least, a starting point for a
      chemical optimization program leading to formulations for the management of the
      tomato leafminer. The application of such products should be conducted according
      to the principles of ecological selectivity.

PMID- 29035635
TI  - Effects of Varying the Step Duration on the Determination of Lactate Thresholds
      in Elite Rowers.
AB  - This study aimed to identify the minimum increment duration required to
      accurately assess 2 distinct lactate thresholds. A total of 21 elite rowers (12
      women and 9 men) participated in this study, and each performed 8 or 9 rowing
      tests comprising 5 progressive incremental tests (3-, 4-, 5-, 7-, or 10-min
      steps) and at least three 30-min constant-intensity maximal lactate steady-state
      assessments. Power output (PO) at lactate threshold 1 was higher in the 3- and 4
      min incremental tests. No other measures were different for lactate threshold 1.
      The PO at the second lactate threshold was different between most tests and was
      higher than the PO at maximal lactate steady state, except for the 10-min
      incremental test. Lactate threshold 2 oxygen consumption was higher in the 3-, 4
      , and 5-min tests, but heart rate (HR) and rating of perceived exertion were not
      different between tests. Peak PO in the incremental tests was inversely related
      to the step durations (r2 = .86, P <= .02). Peak oxygen consumption was higher in
      the shorter (<=5 min) than the longer (>=7 min) incremental tests, whereas peak
      HR was not different between tests. These data suggest that for the methods used
      in this study, incremental exercise tests with step durations <=7 min
      overestimate maximal lactate steady-state exercise intensity, peak physiological
      values are best determined using incremental tests with step durations <=4 min,
      and HR measures are not affected by step duration, and therefore, prescription of
      training HRs can be made using any of these tests.

PMID- 29035636
TI  - Quantification of nitrogen in the liquid fraction and in vitro assessment of
      lysine bioavailability in the solid fraction of soybean meal hydrolysates.
AB  - Soybean meal (SBM) is a product generated from the manufacture of soybean oil and
      has the potential for use as a source of fermentable sugars for ethanol
      production or as a protein source for animal feeds. Knowing the levels of
      nitrogen available from ammonium is a necessary element of the ethanolic
      fermentation process while identifying the levels of essential amino acids such
      as lysine is important in determining usage as a feed source. As such the purpose
      of this study was to quantify total nitrogen and ammonium in the liquid fraction
      of hydrolyzed SBM and to evaluate total and bioavailable lysine in the solid
      fraction of the hydrolyzed SBM. The effects of acid concentration, cellulase and
      beta-glucosidase on total and ammonium nitrogen were studied with analysis
      indicating that higher acid concentrations increased nitrogen compounds with
      ammonium concentrations ranging from 0.20 to 1.24 g L-1 while enzymatic
      treatments did not significantly increase nitrogen levels. Total and bioavailable
      lysine was quantified by use of an auxotrophic gfpmut3 E.coli whole-cell bioassay
      organism incapable of lysine biosynthesis. Acid and enzymatic treatments were
      applied with lysine bioavailability increasing from a base of 82% for untreated
      SBM to up to 97%. Our results demonstrated that SBM has the potential to serve in
      ethanolic fermentation and as an optimal source essential amino acid lysine.

PMID- 29035638
TI  - Evaluation of the effectiveness of a novel gait trainer in increasing the
      functionality of individuals with motor impairment: A case series.
AB  - Regaining the ability to independently ambulate following a physical disability
      can increase functional ability and participation of patients in daily life. Gait
      trainers are assistive devices that enable body support and provide safety during
      gait. However, most conventional gait trainers are pre-configured to a constant
      position, therefore not suitable for practicing sit-to-stand function, and
      require assistance from a caregiver in order to mount the device from a sitting
      position. We therefore evaluated the effectiveness of a dynamically-adjusting
      gait trainer, designed to provide independence and safety during gait and various
      activities, in both lab setting and at home in four subjects (one female, three
      males, ages 32-79 years) with limited ambulation. Spatiotemporal parameters and
      gait symmetry were recorded, as well as activity levels, actual use of device,
      and satisfaction. Although gait parameters and physical activity levels were not
      notably improved, and in one case were worsened, three subjects reported positive
      experience with the gait trainer. The new gait trainer may have advantages in
      supporting users with limited mobility during walking and various functions and
      decrease the risk for falls. A longer practice time and individual fitting
      process are recommended for better accommodation to the new possibilities.

PMID- 29035639
TI  - Correction to: Thyroid 2016;26:1343-1421. DOI: 10.1089/thy.2016.0229.

PMID- 29035637
TI  - Design and characterization of MP0250, a tri-specific anti-HGF/anti-VEGF
      DARPin(r) drug candidate.
AB  - MP0250 is a multi-domain drug candidate currently being tested in clinical trials
      for the treatment of cancer. It comprises one anti-vascular endothelial growth
      factor-A (VEGF-A), one anti-hepatocyte growth factor (HGF), and two anti-human
      serum albumin (HSA) DARPin(r) domains within a single polypeptide chain. While
      there is first clinical validation of a single-domain DARPin(r) drug candidate,
      little is known about DARPin(r) drug candidates comprising multiple domains.
      Here, we show that MP0250 can be expressed at 15 g/L in soluble form in E. coli
      high cell-density fermentation, it is stable in soluble/frozen formulation for 2
      years as assessed by reverse phase HPLC, it has picomolar potency in inhibiting
      VEGF-A and HGF in ELISA and cellular assays, and its domains are simultaneously
      active as shown by surface plasmon resonance. The inclusion of HSA-binding
      DARPin(r) domains leads to a favorable pharmacokinetic profile in mouse and
      cynomolgus monkey, with terminal half-lives of ~ 30 hours in mouse and ~ 5 days
      in cynomolgus monkey. MP0250 is thus a highly potent drug candidate that could be
      particularly useful in oncology. Beyond MP0250, the properties of MP0250 indicate
      that multi-domain DARPin(r) proteins can be valuable next-generation drug
      candidates.

PMID- 29035640
TI  - Patients' Acceptance of the Use of Serious Games in Physical Rehabilitation in
      Morocco.
AB  - OBJECTIVE: The aim of this study was to determine whether serious games
      especially customized for physical rehabilitation could be used in daily clinics
      with patients who are not familiar with informatics and/or new technologies and
      whether such a clinical approach would be culturally acceptable within a North
      African population to plan further clinical distribution if the hypothesis
      appears to be positive. MATERIALS AND METHODS: Twenty-one patients participated
      in this study. Experiments were performed in the University Hospital Mohammed VI
      Oujda in Morocco. Patients were asked to perform physical rehabilitation
      exercises with dedicated serious games after their conventional therapy session.
      A questionnaire was used to evaluate patients' habits to rehabilitation exercises
      and satisfaction and expectation about the use of serious games for physical
      rehabilitation. RESULTS: The same problem of low participation in at-home
      exercises was found in Morocco compared to Europe and the United States: 60 (30)%
      of the exercises was performed by the patients in Morocco and 48 (28)% in Europe
      and the United States. Results of this study show that serious games are well
      accepted by the patients (100%) and that it can help during rehabilitation (90%).
      Most of the patients prefer exercises with games than conventional rehabilitation
      exercises. CONCLUSION: Even in a context of low education (participants in this
      study attended school until the age of 10 years old), and low access and
      knowledge about new technology and informatics, rehabilitation exercises within
      serious games seem to be an interesting option to motivate patients during
      rehabilitation with a physiotherapist. Such a system could be installed also at
      home to increase patient's participation.

PMID- 29035641
TI  - Analysis of clinical features of lipoblastoma in children.
AB  - OBJECTIVE: A lipoblastoma is pathologically benign but often recurs. Due to its
      rarity, studies are scarce. The purpose of this study was to investigate the
      clinical characteristics of lipoblastoma occurring in children and to detect any
      correlations with the expression of Ki-67. PARTICIPANTS: From 1998 to 2010, 33
      patients were diagnosed with lipoblastoma at Seoul National University Children's
      Hospital. METHODS: Ki-67 immunohistochemistry staining of the tumor tissue was
      performed. RESULTS: A total of 33 patients (64% males) were enrolled in the
      study, with a mean age of 28 month. Eleven and 22 lesions were deep and
      superficial, respectively. Complete excisions were performed for 30 patients, and
      three underwent incomplete excisions. Two patients who underwent incomplete
      excision subsequently underwent a second operation due to tumor regrowth, and one
      patient had a recurrence despite complete excision. There was no statistically
      significant correlation observed between the tumor size or recurrence and the
      expression of Ki-67. CONCLUSIONS: Lipoblastoma requires an accurate diagnosis and
      operative resection to alleviate the symptoms induced by its growth. Incompletely
      resected tumor may regrow; therefore, complete excision is the treatment of
      choice. Continuous follow-up is needed to monitor for recurrence of disease, even
      after a complete excision.

PMID- 29035642
TI  - Racial and Ethnic Disparities in Cancer Survival: The Contribution of Tumor,
      Sociodemographic, Institutional, and Neighborhood Characteristics.
AB  - Purpose Racial/ethnic disparities in cancer survival in the United States are
      well documented, but the underlying causes are not well understood. We quantified
      the contribution of tumor, treatment, hospital, sociodemographic, and
      neighborhood factors to racial/ethnic survival disparities in California.
      Materials and Methods California Cancer Registry data were used to estimate
      population-based cancer-specific survival for patients diagnosed with breast,
      prostate, colorectal, or lung cancer between 2000 and 2013 for each racial/ethnic
      group (non-Hispanic black, Hispanic, Asian American and Pacific Islander, and
      separately each for Chinese, Japanese, and Filipino) compared with non-Hispanic
      whites. The percentage contribution of factors to overall racial/ethnic survival
      disparities was estimated from a sequence of multivariable Cox proportional
      hazards models. Results In baseline models, black patients had the lowest
      survival for all cancer sites, and Asian American and Pacific Islander patients
      had the highest, compared with whites. Mediation analyses suggested that stage at
      diagnosis had the greatest influence on overall racial/ethnic survival
      disparities accounting for 24% of disparities in breast cancer, 24% in prostate
      cancer, and 16% to 30% in colorectal cancer. Neighborhood socioeconomic status
      was an important factor in all cancers, but only for black and Hispanic patients.
      The influence of marital status on racial/ethnic disparities was stronger in men
      than in women. Adjustment for all covariables explained approximately half of the
      overall survival disparities in breast, prostate, and colorectal cancer, but it
      explained only 15% to 40% of disparities in lung cancer. Conclusion Overall
      reductions in racial/ethnic survival disparities were driven largely by
      reductions for black compared with white patients. Stage at diagnosis had the
      largest effect on racial/ethnic survival disparities, but earlier detection would
      not entirely eliminate them. The influences of neighborhood socioeconomic status
      and marital status suggest that social determinants, support mechanisms, and
      access to health care are important contributing factors.

PMID- 29035644
TI  - Affordable Care Act, Health Insurance Coverage, and Cancer Outcomes.

PMID- 29035643
TI  - Role of Bone-Modifying Agents in Metastatic Breast Cancer: An American Society of
      Clinical Oncology-Cancer Care Ontario Focused Guideline Update.
AB  - Purpose To update, in collaboration with Cancer Care Ontario (CCO), key
      recommendations of the American Society of Clinical Oncology (ASCO) guideline on
      the role of bone-modifying agents (BMAs) in metastatic breast cancer. This
      focused update addressed the new data on intervals between dosing and the role of
      BMAs in control of bone pain. Methods A joint ASCO-CCO Update Committee conducted
      targeted systematic literature reviews to identify relevant studies. Results The
      Update Committee reviewed three phase III noninferiority trials of dosing
      intervals, one systematic review and meta-analysis of studies of de-escalation of
      BMAs, and two randomized trials of BMAs in control of pain secondary to bone
      metastases. Recommendations Patients with breast cancer who have evidence of bone
      metastases should be treated with BMAs. Options include denosumab, 120 mg
      subcutaneously, every 4 weeks; pamidronate, 90 mg intravenously, every 3 to 4
      weeks; or zoledronic acid, 4 mg intravenously every 12 weeks or every 3 to 4
      weeks. The analgesic effects of BMAs are modest, and they should not be used
      alone for bone pain. The Update Committee recommends that the current standard of
      care for supportive care and pain management-analgesia, adjunct therapies,
      radiotherapy, surgery, systemic anticancer therapy, and referral to supportive
      care and pain management-be applied. Evidence is insufficient to support the use
      of one BMA over another. Additional information is available at
      www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki .

PMID- 29035645
TI  - Factors That Contributed to Black-White Disparities in Survival Among Nonelderly
      Women With Breast Cancer Between 2004 and 2013.
AB  - Purpose To estimate the contribution of differences in demographics, comorbidity,
      insurance, tumor characteristics, and treatment to the overall mortality
      disparity between nonelderly black and white women diagnosed with early-stage
      breast cancer. Patients and Methods Excess relative risk of all-cause death in
      black versus white women diagnosed with stage I to III breast cancer, expressed
      as a percentage and stratified by hormone receptor status for each variable
      (demographics, comorbidity, insurance, tumor characteristics, and treatment) in
      sequentially, propensity-scored, optimally matched patients by using
      multivariable hazard ratios (HRs). Results We identified 563,497 white and black
      women 18 to 64 years of age diagnosed with stage I to III breast cancer from 2004
      to 2013 in the National Cancer Data Base. Among women with hormone receptor
      positive disease, who represented 78.5% of all patients, the HR for death in
      black versus white women in the demographics-matched model was 2.05 (95% CI, 1.94
      to 2.17). The HR decreased to 1.93 (95% CI, 1.83 to 2.04), 1.54 (95% CI, 1.47 to
      1.62), 1.30 (95% CI, 1.24 to 1.36), and 1.25 (95% CI, 1.19 to 1.31) when
      sequentially matched for comorbidity, insurance, tumor characteristics, and
      treatment, respectively. These factors combined accounted for 76.3% of the total
      excess risk of death in black patients; insurance accounted for 37.0% of the
      total excess, followed by tumor characteristics (23.2%), comorbidities (11.3%),
      and treatment (4.8%). Results generally were similar among women with hormone
      receptor-negative disease, although the HRs were substantially smaller.
      Conclusion Matching by insurance explained one third of the excess risk of death
      among nonelderly black versus white women diagnosed with early-stage breast
      cancer; matching by tumor characteristics explained approximately one fifth of
      the excess risk. Efforts to focus on equalization of access to care could
      substantially reduce ethnic/racial disparities in overall survival among
      nonelderly women diagnosed with breast cancer.

PMID- 29035646
TI  - Electronic Health Record Portals adoption: Empirical model based on UTAUT2.
AB  - BACKGROUND: The future of healthcare delivery is becoming more citizen centered,
      as today's user is more active and better informed. Governmental institutions are
      promoting the deployment and use of online services such as Electronic Health
      Record (EHR) portals. This makes the adoption of EHR portals an important field
      to study and understand. OBJECTIVE: The aim of this study is to understand the
      factors that drive individuals to adopt EHR portals. METHODS: This study applies
      the extended unified theory of acceptance and usage technology (UTAUT2) to
      explain patients' individual adoption of EHR portals. An online questionnaire was
      administered. We collected 386 valid responses. RESULTS: The statistically
      significant drivers of behavioral intention are performance expectancy ([Formula:
      see text]=0.17; p < 0.01), effort expectancy ([Formula: see text]=0.17; p <
      0.01), social influence ([Formula: see text]=0.10; p < 0.05), and habit
      ([Formula: see text]=0.37; p < 0.001). Habit ([Formula: see text]=0.28; p <
      0.001) and behavioral intention ([Formula: see text]=0.24; p < 0.001) are the
      statistically significant drivers of technology use. The model explains 52% of
      the variance in behavioral intention and 31% of the variance in technology use.
      CONCLUSIONS: By testing an information technology acceptance model, we are able
      to determine what is more valued by patients when it comes to deciding whether to
      adopt EHR portals or not.

PMID- 29035647
TI  - The Bigger the Hand, the Bigger the Difference? Implications for Testing Strength
      With 2 Popular Handgrip Dynamometers.
AB  - CONTEXT: Studies developed the frail elderly handgrip strength (HGS) diagnostic
      criteria using multiple types of handgrip dynamometers. If different handgrip
      dynamometers report different values, then this would have the potential to
      misclassify people into the wrong diagnostic category. OBJECTIVE: To examine the
      characteristics of HGS measured by 2 standard handgrip dynamometers and to
      investigate the influence of hand size on HGS. SETTING: University research
      laboratory. PARTICIPANTS: A total of 87 young and middle-aged adults between the
      ages of 20 and 60 years participated in this study. MAIN OUTCOME MEASURES:
      Standard methods of HGS measurements were used for hydraulic and Smedley spring
      type dynamometers, although the participants were instructed to maintain an
      upright standing position in both tests. RESULTS: Test-retest reliability of
      hydraulic and Smedley dynamometers provided comparable results to that observed
      with previous studies. However, the difference in HGS between the 2 dynamometers
      (Hydraulic-Smedley difference) was positively associated (r = .670, P < .001)
      with the mean of the 2 dynamometers. The participants who had relatively low HGS
      (at least <35 kg) produced similar HGS values when the 2 dynamometers were
      compared, whereas persons who had relatively higher HGS (at least >45 kg)
      produced greater strength values with the hydraulic compared with the Smedley.
      The hand and palm lengths were weakly correlated (r = .349 and r = .358,
      respectively, both Ps < .001) with the difference in HGS between the 2
      dynamometers. CONCLUSIONS: Test-retest reliability of hydraulic and Smedley
      dynamometers provides comparable results to previous studies. However, the
      difference in HGS between the 2 dynamometers was positively associated with the
      mean of the 2 dynamometers. This Hydraulic-Smedley difference would not affect
      persons who have relatively low HGS (at least <35 kg), while when HGS is
      relatively high, the comparison between dynamometers should be done with caution.

PMID- 29035648
TI  - Treatment of mandibular osteomyelitis in two red-necked wallabies (Macropus
      rufogriseus) by means of intensive long-term parenteral drug administration and
      serial computed tomographic monitoring.
AB  - CASE DESCRIPTION 2 female red-necked wallabies (Macropus rufogriseus) were
      evaluated because of sudden-onset mandibular swelling, ptyalism, and hyporexia.
      CLINICAL FINDINGS Physical examination revealed a mandibular swelling with a
      fluctuant center in both wallabies. Hematologic analysis revealed leukocytosis
      with a mature neutrophilia and monocytosis in one wallaby (case 1) and a slight
      neutrophilia, hyperglobulinemia, and high serum alanine aminotransferase activity
      in the other (case 2). Cytologic examination of the swelling revealed a uniform
      population of gram-negative rods in case 1 and neutrophilic inflammation in case
      2. Radiography revealed a soft tissue mandibular swelling with osteolucency
      around mandibular incisor roots in both wallabies. Computed tomography revealed
      changes consistent with chronic active mandibular osteomyelitis and reactive bone
      formation, but also sequestra formation not appreciable via radiography.
      TREATMENT AND OUTCOME Long-term antimicrobial treatment was initiated with
      clindamycin (17 to 21 mg/kg [7.7 to 9.5 mg/lb], IV, q 12 h for 40 to 55 days) and
      high-dose benzathine penicillin G (80,000 U/kg [36,364 U/lb], SC, q 12 h for 150
      days). Serial CT was performed to evaluate response to treatment and resolution
      of disease. A CT scan 18 months after the initial evaluation revealed complete
      resolution of osteomyelitis and sequestra. CLINICAL RELEVANCE Advanced imaging
      and long-term treatment and management were integral to the successful outcome
      for these wallabies, given that the osseous changes visible on CT images were not
      visible on standard radiographs, guiding therapeutic decision-making. This report
      provides new therapeutic and diagnostic monitoring information to assist
      clinicians with similar cases.

PMID- 29035651
TI  - Letters to the Editor.

PMID- 29035650
TI  - What do pets in New Mexico have to do with one health?

PMID- 29035653
TI  - What Is Your Diagnosis?

PMID- 29035654
TI  - Pathology in Practice.

PMID- 29035655
TI  - Focal uterine T-cell lymphoma in an ovariectomized cat.
AB  - CASE DESCRIPTION A 14-year-old ovariectomized domestic shorthair cat was
      evaluated because of periuria and perineal licking of 3 days' duration. CLINICAL
      FINDINGS On initial examination, an abdominal mass was palpable cranial to the
      urinary bladder. The perineal area was soiled with a blood-tinged mucous fluid.
      Abdominal ultrasonography revealed a vascularized, focal, and circumferential
      thickening of the right uterine horn, involving particularly the muscular layer.
      No evidence of dissemination was noted. TREATMENT AND OUTCOME Hysterectomy was
      performed, revealing a localized, 2.5 * 4-cm firm mass with a smooth surface
      within the right uterine horn. Results of histologic examination and
      immunohistochemical analysis of tissue samples from the mass suggested high-grade
      T-cell uterine lymphoma. Owners declined medical and chemotherapeutic treatments.
      One year later, the cat developed diabetes mellitus, which was medically treated.
      Nineteen months following the uterine lymphoma diagnosis, a central corneal ulcer
      associated with a right retrobulbar mass was diagnosed. The cat was euthanized,
      and the retrobulbar mass was removed. Immunohistochemical staining revealed
      evidence of high-grade B-cell retrobulbar lymphoma. CLINICAL RELEVANCE The
      clinical outcome of this cat with uterine lymphoma was favorable for 19 months
      after diagnosis, with no treatment other than hysterectomy. Whether the same
      outcome could be expected for other cats with this rarely reported neoplasm
      remains to be determined. Uterine lymphoma should be considered as a possible
      cause of dysuria in an ovariectomized cat.

PMID- 29035656
TI  - Clinical, laboratory, and hemostatic findings in cats with naturally occurring
      sepsis.
AB  - OBJECTIVE To characterize clinical and laboratory findings in cats with naturally
      occurring sepsis, emphasizing hemostasis-related findings, and evaluate these
      variables for associations with patient outcomes. DESIGN Prospective,
      observational, clinical study. ANIMALS 31 cats with sepsis and 33 healthy control
      cats. PROCEDURES Data collected included history; clinical signs; results of
      hematologic, serum biochemical, and hemostatic tests; diagnosis; and outcome
      (survival vs death during hospitalization or <= 30 days after hospital
      discharge). Differences between cats with and without sepsis and associations
      between variables of interest and death were analyzed statistically. RESULTS The
      sepsis group included cats with pyothorax (n = 10), septic peritonitis (7),
      panleukopenia virus infection (5), bite wounds (5), abscesses and diffuse
      cellulitis (3), and pyometra (1). Common clinical abnormalities included
      dehydration (21 cats), lethargy (21), anorexia (18), pale mucous membranes (15),
      and dullness (15). Numerous clinicopathologic abnormalities were identified in
      cats with sepsis; novel findings included metarubricytosis, hypertriglyceridemia,
      and high circulating muscle enzyme activities. Median activated partial
      thromboplastin time and plasma D-dimer concentrations were significantly higher,
      and total protein C and antithrombin activities were significantly lower, in the
      sepsis group than in healthy control cats. Disseminated intravascular
      coagulopathy was uncommon (4/22 [18%] cats with sepsis). None of the
      clinicopathologic abnormalities were significantly associated with death on
      multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE Cats with sepsis had
      multiple hematologic, biochemical, and hemostatic abnormalities on hospital
      admission, including several findings suggestive of hemostatic derangement.
      Additional research including larger numbers of cats is needed to further
      investigate these findings and explore associations with outcome.

PMID- 29035657
TI  - Evaluation of mortality rate and predictors of outcome in dogs receiving
      outpatient treatment for parvoviral enteritis.
AB  - OBJECTIVE To determine mortality rates and prognostic factors for dogs with
      parvoviral enteritis receiving outpatient treatment. DESIGN Retrospective case
      series and case-control study. ANIMALS 130 client-owned dogs with a diagnosis of
      parvoviral enteritis between August 1, 2012, and January 31, 2015, that were
      treated with outpatient care. PROCEDURES Medical records were reviewed and data
      extracted regarding dog age, body weight, breed, and vaccination history;
      treatments administered; and short-term (>= 3 day) outcome (determined via
      telephone call with owner). Treatments were administered according to clinician
      preference. Mortality rates were calculated overall and for various signalment
      and treatment groupings and compared. RESULTS 97 (75%) dogs survived and 33 (25%)
      dogs failed to survive for >= 3 days after initial diagnosis of parvoviral
      enteritis. Compared with distributions in the general hospital population,
      Chihuahuas, German Shepherd Dogs, pit bull-type dogs, and males were
      overrepresented. No significant difference was identified between survivors and
      nonsurvivors regarding age, body weight, or sex. Dogs prescribed a caloric
      supplement fed every 2 to 4 hours had a mortality rate of 19% (16/85). Most of
      these dogs had also received fluids administered SC, an antiemetic, and
      antimicrobials. CONCLUSIONS AND CLINICAL RELEVANCE Clinicians should note the 25%
      mortality rate of the dogs with parvoviral enteritis that received outpatient
      care in this study setting when discussing treatment options with owners of
      affected dogs who are financially unable to pursue hospitalization.

PMID- 29035658
TI  - Toward an evidence-based approach to stress management for veterinarians and
      veterinary students.

PMID- 29035659
TI  - Animal Behavior Case of the Month.

PMID- 29035660
TI  - Pathology in Practice.

PMID- 29035662
TI  - Treatment of medial shoulder joint instability in dogs by extracapsular
      stabilization with a prosthetic ligament: 39 cases (2008-2013).
AB  - OBJECTIVE To investigate clinical outcomes for dogs surgically treated for medial
      shoulder joint instability (MSI) by extracapsular stabilization with a prosthetic
      ligament. DESIGN Retrospective multicenter case series. ANIMALS 39 client-owned
      dogs. PROCEDURES Medical records of 3 veterinary medical centers were searched to
      identify dogs with MSI diagnosed by clinical examination and arthroscopic
      assessment and treated by extracapsular stabilization with a prosthetic ligament.
      A minimum 6-month follow-up period was required for study inclusion. Signalment,
      function or use of the dog, duration of clinical signs, clinical and diagnostic
      imaging data, MSI grade (1 [mild] to 4 [complete luxation]), follow-up duration,
      complications, and outcome data were recorded. RESULTS All grades of MSI were
      represented. Implants were placed successfully in all dogs. Complications (4
      major and 2 minor) were recorded for 6 of 39 (15%) dogs; all were treated
      successfully. Function at the time of last follow-up (6 to 68 months) was deemed
      full in 30 of 39 (77%) dogs and acceptable in 9 (23%). CONCLUSIONS AND CLINICAL
      RELEVANCE Surgical treatment of MSI in dogs by extracapsular stabilization with a
      prosthetic ligament was associated with a complication rate considered acceptable
      for orthopedic procedures. All patient outcomes were considered successful.

PMID- 29035661
TI  - Outcome of laparoscopic ovariohysterectomy or ovariectomy in dogs with von
      Willebrand disease or factor VII deficiency: 20 cases (2012-2014).
AB  - OBJECTIVE To describe surgical techniques and perioperative management of dogs
      with von Willebrand disease (VWD) or factor VII (FVII) deficiency undergoing
      laparoscopic ovariohysterectomy or ovariectomy and evaluate outcomes. DESIGN
      Retrospective case series. ANIMALS 20 client-owned dogs with VWD (n = 16) or FVII
      deficiency (4). PROCEDURES Dogs with VWD or FVII deficiency that underwent
      laparoscopic ovariohysterectomy or ovariectomy between 2012 and 2014 were
      retrospectively identified via a multi-institutional review of medical records.
      RESULTS Median expression of von Willebrand factor was 19% (interquartile range,
      18% to 30%). All 16 dogs with VWD were Doberman Pinschers, and all were
      pretreated with desmopressin; 4 also received cryoprecipitate. One of 4 dogs with
      FVII deficiency received plasma preoperatively, and 1 was treated with
      desmopressin; 2 dogs received no preoperative treatment. Laparoscopic ovariectomy
      was performed in 9 dogs with VWD and 2 dogs with FVII deficiency, laparoscopic
      ovariectomy with gastropexy was performed in 6 dogs with VWD and 1 dog with FVII
      deficiency, and laparoscopic-assisted ovariohysterectomy was performed in 1 dog
      with VWD and 1 dog with FVII deficiency. Iatrogenic splenic laceration requiring
      conversion to laparotomy occurred during trocar insertion in 1 dog with VWD. No
      postoperative complications, including signs of hemorrhage, were reported for any
      dogs. CONCLUSIONS AND CLINICAL RELEVANCE Laparoscopic ovariohysterectomy or
      ovariectomy in dogs with VWD or FVII deficiency pretreated with desmopressin,
      cryoprecipitate, or plasma transfusions were not associated with clinical signs
      of hemorrhage, suggesting that minimally invasive ovariohysterectomy or
      ovariectomy may be considered in female dogs affected with these coagulopathies.

PMID- 29035663
TI  - Contrast fluoroscopic evaluation of gastrointestinal transit times with and
      without the use of falconry hoods in red-tailed hawks (Buteo jamaicensis).
AB  - OBJECTIVE To evaluate gastrointestinal transit times in red-tailed hawks (Buteo
      jamaicensis) by use of contrast fluoroscopic imaging and investigate the effect
      of falconry hooding in these hawks on gastrointestinal transit time. DESIGN
      Prospective, randomized, blinded, complete crossover study. ANIMALS 9 healthy red
      tailed hawks. PROCEDURES Hawks were gavage-fed a 30% weight-by-volume barium
      suspension (25 mL/kg [11.3 mL/lb]) into the crop. Fluoroscopic images were
      obtained at multiple time points after barium administration. Time to filling and
      emptying of various gastrointestinal tract organs and overall transit time were
      measured. The effect of hooding (hooded vs nonhooded) on these variables was
      assessed in a randomized complete crossover design. RESULTS In nonhooded birds,
      overall gastrointestinal transit time ranged from 30 to 180 minutes (mean +/- SD,
      100 +/- 52 min). Time to complete crop emptying ranged from 30 to 180 minutes (83
      +/- 49 min). Contrast medium was present in the ventriculus in all birds within 5
      minutes of administration and in the small intestines within 5 to 15 minutes
      (median, 5 min). Hooding of red-tailed hawks resulted in a significant delay of
      complete crop emptying (no hood, 83 +/- 49 minutes; hood, 133 +/- 48 minutes),
      but no significant effects of hooding were found on other measured variables.
      CONCLUSIONS AND CLINICAL RELEVANCE These results indicated that overall
      gastrointestinal transit times are faster in red-tailed hawks than has been
      reported for psittacines and that the use of a falconry hood in red-tailed hawks
      may result in delayed crop emptying. Hooding did not exert significant effects on
      overall gastrointestinal transit time in this raptorial species.

PMID- 29035664
TI  - Understanding of how older adults with low vision obtain, process, and understand
      health information and services.
AB  - INTRODUCTION: Twenty-five years after the Americans with Disabilities Act, there
      has still been a lack of advancement of accessibility in healthcare for people
      with visual impairments, particularly older adults with low vision. This study
      aims to advance understanding of how older adults with low vision obtain,
      process, and use health information and services, and to seek opportunities of
      information technology to support them. METHODS: A convenience sample of 10 older
      adults with low vision participated in semi-structured phone interviews, which
      were audio-recorded and transcribed verbatim for analysis. RESULTS: Participants
      shared various concerns in accessing, understanding, and using health
      information, care services, and multimedia technologies. Two main themes and nine
      subthemes emerged from the analysis. DISCUSSION: Due to the concerns, older
      adults with low vision tended to fail to obtain the full range of all health
      information and services to meet their specific needs. Those with low vision
      still rely on residual vision such that multimedia-based information which can be
      useful, but it should still be designed to ensure its accessibility, usability,
      and understandability.

PMID- 29035665
TI  - Like an extended family: Relationships that emerge when older caregivers use
      written messages to communicate in an ICT-based healthcare service.
AB  - OBJECTIVE: To explore the relationships that emerge amongst caregivers of persons
      with dementia and stroke when caregivers use written messages as their
      communication tool in a closed information and communication technology (ICT)
      based support group. METHODS: An explorative design with a qualitative approach
      was used that applied systematic text condensation (STC) to analyse 173 written
      messages extracted from a web forum. RESULTS: Empathetic, empowering and familiar
      relationships emerged amongst peers of older caregivers when the caregivers used
      written messages as their communication tool. The empathetic relationship was
      characterised by sincerity and openness when the caregivers shared emotions
      related to caregiving. The empowering relationship reflected a fellowship based
      on solidarity influenced by a sense of optimism and a willingness to share
      knowledge to support one another in overcoming challenges. In the familiar
      relationship, the caregivers were thoughtful and good-humoured with one another
      and displayed an attitude of consideration towards one another, as in an extended
      family. PRACTICE IMPLICATION: The use of computer-mediated communication in
      health care service will change the context of establishing and maintaining
      interpersonal relationships. Therefore, greater knowledge regarding how the peers
      of caregivers interact with one another is vital so nurses may better support and
      educate ICT-based support groups.

PMID- 29035666
TI  - Examination of Risk for Sleep-Disordered Breathing Among College Football
      Players.
AB  - CONTEXT: Professional football linemen are at risk for sleep-disordered breathing
      (SDB) compared with other types of athletes. It is currently unknown whether
      college football linemen display a similar risk profile. OBJECTIVE: (1) To
      determine for the first time whether college football linemen show risk for SDB
      and (2) test the hypothesis that SDB risk is higher in college football linemen
      compared with an athletic comparison group. DESIGN: Descriptive laboratory study.
      SETTING: The Health Risk Assessment Laboratory. PARTICIPANTS: Male football
      linemen (n = 21) and track (n = 19) Division I athletes between the ages of 18
      and 22 years. INTERVENTIONS: Participants completed the Multivariable Apnea
      Prediction Index and Epworth Sleepiness Scale surveys, validated measures of
      symptoms of sleep apnea and daytime sleepiness, respectively. Neck and waist
      circumferences, blood pressure, Modified Mallampati Index (MMPI), and tonsil size
      were determined, followed by body composition assessment using dual-energy X-ray
      absorptiometry. MAIN OUTCOME MEASURES: Scores from surveys, anthropometric data,
      MMPI, and body composition. RESULTS: Survey data demonstrated a deficiency in
      sleep quality and efficiency, coinciding with increased self-reported symptoms of
      apnea (Multivariable Apnea Prediction Index = 0.78) in college linemen relative
      to track athletes. Neck circumference (44.36 cm), waist circumference (107.07
      cm), body mass index (35.87 kg/m2), and percent body fat (29.20%), all of which
      exceeded the clinical predictors of risk for obstructive sleep apnea, were
      significantly greater in linemen compared with track athletes. Multivariable
      Apnea Prediction variables were significantly correlated with MMPI, neck
      circumference, percent body fat, body mass index, and systolic blood pressure (r
      >= .31, P < .05), indicating that college football linemen are at increased risk
      for SDB. CONCLUSIONS: Risk factors for SDB recognized in professional football
      linemen are also present at the college level. Screening may minimize present or
      future risk for SDB, as well as the downstream risk of SDB-associated metabolic
      and cardiovascular disease.

PMID- 29035667
TI  - Why doctors consider leaving UK medicine: qualitative analysis of comments from
      questionnaire surveys three years after graduation.
AB  - Objective To report the reasons why doctors are considering leaving medicine or
      the UK. Design Questionnaire survey. Setting UK. Participants Questionnaires were
      sent three years after graduation to all UK medical graduates of 2008 and 2012.
      Main outcome measures Comments from doctors about their main reasons for
      considering leaving medicine or the UK (or both). Results The response rate was
      46.2% (5291/11,461). Among the 60% of respondents who were not definitely intent
      on remaining in UK medicine, 50% were considering working in medicine outside the
      UK and 10% were considering leaving medicine. Among those considering working in
      medicine outside the UK, the most commonly cited reasons were to gain wider
      experience, that things would be 'better' elsewhere and a negative view of the
      National Health Service and its culture, state and politics. Other reasons
      included better training or job opportunities, better pay and conditions, family
      reasons and higher expectations. Three years after graduation, doctors surveyed
      in 2015 were significantly more likely than doctors surveyed in 2011 to cite
      factors related to the National Health Service, to pay and conditions, to their
      expectations and to effects on work-life balance and patient care. Among those
      considering leaving medicine, the dominant reason for leaving medicine was a
      negative view of the National Health Service (mentioned by half of those in this
      group who commented). Three years after graduation, doctors surveyed in 2015 were
      more likely than doctors surveyed in 2011 to cite this reason, as well as
      excessive hours and workload, and financial reasons. Conclusions An increasingly
      negative view is held by many doctors of many aspects of the experience of being
      a junior doctor in the National Health Service, and the difficulty of delivering
      high-quality patient care within what many see as an under-funded system. Policy
      changes designed to encourage more doctors to remain should be motivated by a
      desire to address these concerns by introducing real improvements to resources,
      staffing and working conditions.

PMID- 29035668
TI  - Improving how secondary care and general practice in England work together:
      requirements in the NHS Standard Contract.

PMID- 29035669
TI  - Translational health policy: towards an integration of academia and policy.

PMID- 29035670
TI  - Sticking to principles and anticipating outcomes.

PMID- 29035671
TI  - Selection of electrogenic bacteria for microbial fuel cell in removing Victoria
      blue R from wastewater.
AB  - This study was conducted to select electrogenic bacteria from wastewater sludge.
      Phylogenetic analysis revealed that Proteobacteria was the dominant phylum in the
      microbial fuel cell (MFC) during the decomposition process of organic pollutants.
      Five culturable bacteria strains - namely, Bacillus subtilis, Flavobacterium sp.,
      Aeromonas hydrophila, Citrobacter freundii, and Stenotrophomonas sp. - have a
      double potential in dye removal and electricity generation. We inoculated the
      mixed electrogenic bacteria at a specific ratio and treated them with a
      triphenylmethane dye, Victoria blue R (VBR), to evaluate their electricity
      generation ability for the artificial and real wastewater. The results of the VBR
      shock-loading experiment indicated that the inoculated MFC could adapt to shock
      loading in 1-2 days and exhibited high removal efficiency (95-100%) for 100-800
      mg L-1 VBR with a power density of 8.62 +/- 0.10 to 34.81 +/- 0.25 mW m-2. The
      selected electrogenic bacteria in the MFC could use VBR as only electron donor
      for power generation. The matrix effects of the real wastewater on VBR removal
      and electricity generation of MFC were insignificant. VBR degradation by the
      electrogenic bacteria involves a stepwise demethylation process to yield
      partially dealkylated VBR species. In addition, these results demonstrate the
      feasibility of inoculating culturable bacteria strains to develop an efficient
      MFC for purifying wastewater.

PMID- 29035672
TI  - Overview of Home Parenteral Nutrition: An Update.
AB  - The trend in modern medicine is to transition care from the hospital to home or
      other nonacute settings as soon as possible. Increasingly, nutrition support
      professionals are being asked to help facilitate discharge and/or manage patients
      who require prolonged intravenous fluid and/or nutrition after having been
      stabilized during a hospitalization. This updated tutorial reviews many of the
      concepts and challenges that must be considered for successful care that helps to
      focus on the patients and their quality of life.

PMID- 29035674
TI  - The startup performance and microbial distribution of an anaerobic baffled
      reactor (ABR) treating medium-strength synthetic industrial wastewater.
AB  - In this study, an anaerobic baffled reactor (ABR) with seven chambers was applied
      to treat medium-strength synthetic industrial wastewater (MSIW). The performance
      of startup and shock test on treating MSIW was investigated. During the
      acclimation process, the chemical oxygen demand (COD) of MSIW gradually increased
      from 0 to 2,000 mg L-1, and the COD removal finally reached 90%. At shock test,
      the feeding COD concentration increased by one-fifth and the reactor adapted very
      well with a COD removal of 82%. In a stable state, Comamonas, Smithella,
      Syntrophomonas and Pseudomonas were the main populations of bacteria, while the
      predominant methanogen was Methanobacterium. The results of chemical and
      microbiological analysis indicated the significant advantages of ABR, including
      buffering shocks, separating stages with matching microorganisms and promoting
      syntrophism. Meanwhile, the strategies for acclimation and operation were of
      great importance. Further work can test reactor performance in the treatment of
      actual industrial wastewater.

PMID- 29035673
TI  - Extracellular pyridine nucleotides as immune elicitors in arabidopsis.
AB  - The pyridine nucleotides nicotinamide adenine dinucleotide (NAD) and NAD
      phosphate (NADP) are coenzymes that function in both metabolic reactions and
      intracellular signaling. Emerging evidence from animal research indicates that
      NAD(P) also acts in the extracellular space (ECS). We have shown in the model
      plant Arabidopsis that (1) exogenous NAD(P) induces immune responses, (2)
      pathogen infection causes leakage of intracellular NAD(P) into the extracellular
      fluid at concentrations sufficient to induce immune responses, and (3) removal of
      extracellular NAD(P) [eNAD(P)] by expressing the human NAD(P)-metabolizing
      ectoenzyme CD38 partially compromises systemic acquired resistance. Based on
      these results, we hypothesize that eNAD(P) is a novel damage-associated molecular
      pattern (DAMP) in plants; during plant-microbe interaction, intracellular NAD(P)
      is released from dead or dying cells into the ECS where it interacts with the
      adjacent healthy cells' surface receptors/targets, which in turn activate
      downstream specific immune signaling pathways. Our recent identification of LecRK
      I.8, a lectin receptor kinase, as the first cell surface NAD+-binding receptor
      has provided compelling evidence for this hypothesis. Further identification of
      cell surface eNAD(P) receptors/targets and their downstream signaling components
      in Arabidopsis as well as determination of the generality of eNAD(P) signaling in
      crops will help establish eNAD(P) as a conserved DAMP in plants.

PMID- 29035675
TI  - Practical considerations in clinical strategy to support the development of
      injectable drug-device combination products for biologics.
AB  - The development of an injectable drug-device combination (DDC) product for
      biologics is an intricate and evolving process that requires substantial
      investments of time and money. Consequently, the commercial dosage form(s) or
      presentation(s) are often not ready when pivotal trials commence, and it is
      common to have drug product changes (manufacturing process or presentation)
      during clinical development. A scientifically sound and robust bridging strategy
      is required in order to introduce these changes into the clinic safely. There is
      currently no single developmental paradigm, but a risk-based hierarchical
      approach has been well accepted. The rigor required of a bridging package depends
      on the level of risk associated with the changes. Clinical
      pharmacokinetic/pharmacodynamic comparability or outcome studies are only
      required when important changes occur at a late stage. Moreover, an injectable
      DDC needs to be user-centric, and usability assessment in real-world clinical
      settings may be required to support the approval of a DDC. In this review, we
      discuss the common issues during the manufacturing process and presentation
      development of an injectable DDC and practical considerations in establishing a
      clinical strategy to address these issues, including key elements of clinical
      studies. We also analyze the current practice in the industry and review relevant
      and status of regulatory guidance in the DDC field.

PMID- 29035676
TI  - The Molecular Mechanism and Neuroprotective Effect of Dihydrocapsaicin-Induced
      Mild Hypothermia After Cardiopulmonary Resuscitation in Rats.
AB  - To investigate the molecular mechanism of dihydrocapsaicin (DHC)-induced mild
      hypothermia in rats, and to compare its protective effect on the central nervous
      system with that of a conventional method of inducing hypothermia, 24 healthy
      male Sprague Dawley rats were randomly divided into four groups based on the
      following conditions: control group, cardiopulmonary resuscitation (CPR) group,
      body surface cooling group, and DHC group. Tracheal clipping was used to mimic
      asphyxia arrest. Rats were assessed for their neurological deficit scores. After
      sacrifice, immunohistochemical staining was used to examine caspase-3 expression
      in the cerebral cortex and TRPV1 (transient receptor potential vanilloid
      subfamily, member 1) expression in the hypothalamus. Terminal TdT-mediated dUTP
      biotin nick end labeling (TUNEL) staining was used to evaluate cell apoptosis in
      the cerebral cortex. Furthermore, intracellular Ca2+ concentration in the
      hypothalamus and arginine vasopressin (AVP) concentration in ventral septal
      tissues were also detected in these four groups. Results of our study showed that
      neurological deficit scores in the DHC group were significantly higher than those
      in the CPR and body surface cooling groups (p < 0.05). Caspase-3 expression in
      the cerebral cortex of control group rats was significantly lower than that in
      other three groups (p < 0.05). Hypothalamic TRPV1 expression, hypothalamic
      intracellular Ca2+ concentration, and AVP concentration in the ventral septum in
      the DHC group were significantly higher than that in the other three groups (p <
      0.05). Within these three groups, there were significantly fewer apoptotic cells
      in the DHC and body surface cooling group rats than in the CPR group rats (p <
      0.05). DHC has the neuroprotective effect. DHC induced mild hypothermia and
      reduces apoptosis through a mechanism whereby DHC activates TRPV1 on hypothalamic
      cells to cause a large Ca2+ influx, which alters corresponding physiological
      functions and causes the release of AVP to induce hypothermia.

PMID- 29035677
TI  - Effectiveness of a Smartphone Application for the Management of Metabolic
      Syndrome Components Focusing on Weight Loss: A Preliminary Study.
AB  - BACKGROUND: There are inconsistent results for the effectiveness of using
      smartphone applications (apps) or websites on weight loss. We investigated the
      efficacy of a smartphone intervention using a designated app that utilizes a
      lifestyle intervention-focused approach, including a human coaching element,
      toward weight loss in overweight or obese Korean adults. METHODS: One hundred
      four adults aged 20-60 years with a body mass index >=23 kg/m2, who signed up for
      a smartphone program for weight loss (using the Noom app), were recruited.
      Participants received an in-person orientation about the study and app use, and a
      baseline blood sample was obtained. The in-app intervention with daily behavior
      and nutrition education content and coaching lasted 15 weeks. The primary
      endpoint of the study was a change in weight. The secondary endpoints were
      changes in metabolic risk factors such as blood pressure, waist circumference,
      and glucose and lipid profiles. Body composition changes were also assessed, and
      body weight at 52 weeks was measured to ascertain long-term effects. RESULTS:
      Participants showed a clinically significant weight loss effect of -7.5% at the
      end of the 15-week program (P < 0.001), and at a 52-week follow-up, a weight loss
      effect of -5.2% was maintained. At 15 weeks, percent body fat and visceral fat
      decreased by -6.0 +/- 5.4% and -3.4 +/- 2.7 kg, respectively (both P < 0.001).
      Fasting glucose level also decreased significantly by -5.7 +/- 14.6 mg/dL at 15
      weeks. Lipid parameters showed significant improvements, except for high-density
      lipoprotein cholesterol. The frequency of logging meals and exercise was
      associated with body fat loss. CONCLUSIONS: This advanced smartphone app was a
      useful tool to maintain weight loss in overweight or obese people.

PMID- 29035678
TI  - The relationships between impact location and post-impact ball speed, bat
      torsion, and ball direction in cricket batting.
AB  - Three-dimensional kinematic data of bat and ball were recorded for 239 individual
      shots performed by twenty batsmen ranging from club to international standard.
      The impact location of the ball on the bat face was determined and assessed
      against the resultant instantaneous post-impact ball speed and measures of post
      impact bat torsion and ball direction. Significant negative linear relationships
      were found between post-impact ball speed and the absolute distance of impact
      from the midline medio-laterally and sweetspot longitudinally. Significant cubic
      relationships were found between the distance of impact from the midline of the
      bat medio-laterally and both a measure of bat torsion and the post-impact ball
      direction. A "sweet region" on the bat face was identified whereby impacts within
      2 cm of the sweetspot in the medio-lateral direction, and 4.5 cm in the
      longitudinal direction, caused reductions in ball speed of less than 6% from the
      optimal value, and deviations in ball direction of less than 10 degrees  from the
      intended target. This study provides a greater understanding of the margin for
      error afforded to batsmen, allowing researchers to assess shot success in more
      detail, and highlights the importance of players generating consistently central
      impact locations when hitting for optimal performance.

PMID- 29035679
TI  - Performance and membrane fouling of a step-fed submerged membrane sequencing
      batch reactor treating swine biogas digestion slurry.
AB  - To identify the performance of step-fed submerged membrane sequencing batch
      reactor (SMSBR) treating swine biogas digestion slurry and to explore the
      correlation between microbial metabolites and membrane fouling within this novel
      reactor, a lab-scale step-fed SMSBR was operated under nitrogen loading rate of
      0.026, 0.052 and 0.062 g NH4+-N (gVSS.d)-1. Results show that the total removal
      efficiencies for NH4+-N, total nitrogen and chemical oxygen demand in the reactor
      (>94%, >89% and >97%, respectively) were high during the whole experiment.
      However, the cycle removal efficiency of NH4+-N decreased significantly when the
      nitrogen loading rate was increased to 0.062 g NH4+-N (gVSS.d)-1. The total
      removal efficiency of total phosphorus in the step-fed SMSBR was generally higher
      than 75%, though large fluctuations were observed during the experiments. In
      addition, the concentrations of microbial metabolites, i.e., soluble microbial
      products (SMP) and extracellular polymeric substances (EPS) from activated sludge
      increased as nitrogen loading rate increased, both showing quadratic equation
      correlations with viscosity of the mixed liquid in the step-fed SMSBR (both R2 >
      0.90). EPS content was higher than SMP content, while protein (PN) was detected
      as the main component in both SMP and EPS. EPS PN was found to be well correlated
      with transmembrane pressure, membrane flux and the total membrane fouling
      resistance. Furthermore, the three-dimensional excitation-emission matrix
      fluorescence spectroscopy results suggested the tryptophan-like protein as one of
      the main contributors to the membrane fouling. Overall, this study showed that
      the step-fed SMSBR could be used to treat swine digestion slurry at nitrogen
      loading rate of 0.052 g NH4+-N (gVSS.d)-1, and the control strategy of membrane
      fouling should be developed based on reducing the tryptophan-like PN in EPS.

PMID- 29035681
TI  - Cervical spine disease in surgeons performing arthroscopy or laparoscopy.
AB  - : Minimal research exists regarding cervical spine disorders in surgeons who
      perform endoscopy. A confidential on-line survey regarding neck pain (NP), spine
      disease (SD), and radiculopathy/myelopathy (R/M) was sent to 722 surgeons from a
      managed, group-based health care system. 415 responded. 361 had endoscopy
      experience, of whom 24.4% had NP, 20.8% SD, and 3.9% R/M. Most respondents were
      less than 50 years of age (62.3%), and male (65.7%). Significant risk factors for
      NP included older age and female, whereas OB/Gyn specialty, increased age and job
      stress were for SD. After adjusting for age and gender, significant risk factors
      for NP and SD included greater surgeon experience. After also adjusting for job
      stress, significant risk factors for SD included increased surgeon experience and
      higher frequency of endoscopies. No association was found between use of digital
      OR. Endoscopy appears to place surgeons at higher risk of cervical disease. LEVEL
      OF EVIDENCE: Level 3.

PMID- 29035682
TI  - The role of miR319a and its target gene TCP4 in the regulation of pistil
      development in Prunus mume.
AB  - The microRNAs (miRNAs) comprise a broad class of non-coding small endogenous RNAs
      that are associated with many biological processes through the regulation of
      target genes, such as leaf morphogenesis and polarity, biotic and abiotic stress
      responses, and root and flower development. We identified a miRNA that affects
      flower development, miR319a, in Prunus mume. The Pm-miR319a target, Pm-TCP4, was
      validated by 5'RACE. The higher expression of Pm-TCP4 in imperfect flowers showed
      that Pm-TCP4 might promote pistil abortion. Further experiments showed that Pm
      miR319a negatively regulates the expression of Pm-TCP4 mRNAs and affected pistil
      development. Sixteen downstream genes of Pm-TCP4 related to flower development
      were predicted. Previous studies have shown that they have an impact on the
      development of pistils. In this study it was established that Pm-miR319a
      indirectly regulates the development of pistils by regulating its target gene Pm
      TCP4.

PMID- 29035683
TI  - Mapping of quantitative trait loci associated with size, shape, and parr mark
      traits using first- and second-generation backcrosses between European and North
      American Atlantic salmon (Salmo salar).
AB  - Little is known about the genetic architecture of traits important for salmonid
      restoration ecology. We mapped quantitative trait loci (QTL) using single
      nucleotide polymorphisms (SNPs) for juvenile body length, weight, shape, and
      vertical skin pigmentation patterns (parr marks) within three hybrid backcross
      families between European and North American subspecies of Atlantic salmon.
      Amounts of variation in skin colour and pattern quantified in the two second
      generation transAtlantic families exceeded the ranges seen in purebred
      populations. GridQTL analyses using low-density female-specific linkage maps
      detected QTL showing experiment-wide significance on Ssa02, Ssa03, Ssa09, Ssa11,
      Ssa19, and Ssa26/28 for both length and weight; on Ssa04 and Ssa23 for parr mark
      number; on Ssa09 and Ssa13 for parr mark contrast; and on Ssa05, Ssa07, Ssa10,
      Ssa11, Ssa18, Ssa23, and Ssa26/28 for geometric morphometric shape coordinates.
      Pleiotrophic QTL on Ssa11 affected length, weight, and shape. No QTL was found
      that explained more than 10% of the phenotypic variance in pigmentation or shape
      traits. Each QTL was approximately positioned on the physical map of the Atlantic
      salmon genome. Some QTL locations confirmed previous studies but many were new.
      Studies like ours may increase the success of salmon restoration projects by
      enabling better phenotypic and genetic matching between introduced and extirpated
      strains.

PMID- 29035684
TI  - SOX10 induces epithelial-mesenchymal transition and contributes to nasopharyngeal
      carcinoma progression.
AB  - OBJECTIVE: The aim of this study was to investigate the role of SOX10 in
      nasopharyngeal carcinoma (NPC) and the underlying molecular mechanisms. METHODS:
      The expression of SOX10 was initially assessed in human NPC tissues and a series
      of NPC cell lines through quantitative real-time PCR (qRT-PCR) and Western blot.
      Then, cell proliferation, cycle, migration, and the invasiveness of NPC cells
      with knockdown of SOX10 were examined by MTT, flow cytometry, and Transwell
      migration and invasion assays, respectively. Finally, nude mice tumorigenicity
      experiments were performed to evaluate the effects of SOX10 on NPC growth and
      metastasis in vivo. RESULTS: SOX10 was significantly increased in NPC tissues and
      cell lines. In-vitro experiments revealed that loss of SOX10 obviously inhibited
      cell proliferation, migration, and invasiveness, as well as the epithelial
      mesenchymal transition (EMT) process in NPC cells. In-vivo experiments further
      demonstrated that disrupted SOX10 expression restrained NPC growth and
      metastasis, especially in lung and liver. CONCLUSION: Taken together, our data
      confirmed the role of SOX10 as an oncogene in NPC progression, and revealed that
      SOX10 may serve as a novel biomarker for diagnosis of NPC, as well as a potential
      therapeutic target against this disease.

PMID- 29035685
TI  - Mechanistic effect of human umbilical cord blood derived mesenchymal stem cells
      on the submandibular salivary gland in ovariectomized rats.
AB  - We performed this study to understand the effect of human umbilical cord blood
      derived mesenchymal stem cells (hUCB-MSCs) on the submandibular gland after
      bilateral ovariectomy. For this, 21 adult female rats were distributed equally
      among 3 groups: the sham-operated group (SHAM); the ovariectomized group (OVX);
      and the OVX group that received repeated intravenous injections of the hUCB-MSCs
      (OVX + hUCB-MSCs). We used reverse transcription - PCR to analyze for the gene
      expression of AQPs 3, 4, 5, and BMP-6. The cellular localization and expression
      of human CD105, human CD34, proliferating nuclear antigen (PCNA), single-stranded
      DNA (ss-DNA), caspase 3, AQP1, and alpha smooth muscle actin (alpha-SMA) were
      determined immunohistochemically. In the OVX group, a significant decrease in the
      gene expression of AQP3, AQP4, and BMP6, as well as the acinar area % was
      detected, while area % of granular convoluted tubules (GCTs) showed a significant
      increase. A significant decrease in area % staining positively for AQP1 and alpha
      SMA was noted. An obvious improvement in the structure of the submandibular gland
      was demonstrated in the group injected with hUCB-MSCs, as well as a significant
      increase in the gene expression of AQP3, AQP4, and BMP6. The acinar and GCT area
      %, as well as the different measured markers, were relatively normal. This
      demonstrates that E2-deficiency induces structural changes to the submandibular
      gland. Moreover, a definite amelioration of the structure and function of the
      submandibular gland was detected after the administration of hUCB-MSCs.

PMID- 29035686
TI  - The Human Odontoblast Cell Layer and Dental Pulp Proteomes and N-Terminomes.
AB  - The proteome and N-terminome of the human odontoblast cell layer were identified
      for the first time by shotgun proteomic and terminal amine isotopic labeling of
      substrates (TAILS) N-terminomic analyses, respectively, and compared with that of
      human dental pulp stroma from 26 third molar teeth. After reverse-phase liquid
      chromatography-tandem mass spectrometry, >170,000 spectra from the shotgun and
      TAILS analyses were matched by 4 search engines to 4,888 and 12,063 peptides in
      the odontoblast cell layer and pulp stroma, respectively. Within these peptide
      groups, 1,543 and 5,841 protein N-termini, as well as 895 and 2,423 unique
      proteins, were identified with a false discovery rate of <=1%. Thus, the human
      dental pulp proteome was expanded by 974 proteins not previously identified among
      the 4,123 proteins in our 2015 dental pulp study. Further, 222 proteins of the
      odontoblast cell layer were not found in the pulp stroma, suggesting many of
      these proteins are synthesized only by odontoblasts. When comparing the proteomes
      of older and younger donors, differences were more apparent in the odontoblast
      cell layer than in the dental pulp stroma. In the odontoblast cell layer
      proteome, we found proteomic evidence for dentin sialophosphoprotein, which is
      cleaved into dentin sialoprotein and dentin phosphoprotein. By exploring the
      proteome of the odontoblast cell layer and expanding the known dental pulp
      proteome, we found distinct proteome differences compared with each other and
      with dentin. Moreover, between 61% and 66% of proteins also occurred as
      proteoforms commencing with a neo-N-terminus not annotated in UniProt. Hence,
      TAILS increased proteome coverage and revealed considerable proteolytic
      processing, by identifying stable proteoforms in these dynamic dental tissues.
      All mass spectrometry raw data have been deposited to ProteomeXchange with the
      identifier <PXD006557>, with the accompanying metadata at Mendeley Data (
      https://data.mendeley.com/datasets/b57zfh6wmy/1 ).

PMID- 29035687
TI  - Acute glutamine ingestion modulates lymphocytic responses to exhaustive exercise
      in the heat.
AB  - The purpose of this study was to determine if acute intake of glutamine modulates
      homeostatic, hematologic, immune, and inflammatory responses to exhaustive
      exercise in the heat. Thirteen healthy, untrained young men participated in this
      randomized, double-blind, placebo-controlled, crossover study. They served as
      their own control and completed 2 trials of treadmill exercise at 40% maximal
      oxygen uptake to exhaustion in a hot environment (temperature, 38.0 +/- 1.0 
      degrees C; relative humidity, 60.0% +/- 5.0%; oxygen, 20.8%) following placebo
      (PLA) and glutamine (GLN) consumption. Heart rate, gastrointestinal temperature,
      forehead temperature, the rating of perceived exertion, and body weight were
      measured. Blood samples were collected before and after exercise. After
      exhaustive exercise in the heat (PLA vs. GLN: 42.0 +/- 9.5 vs. 39.6 +/- 7.8 min,
      p > 0.05), significant changes in homeostatic, hematologic, and immune parameters
      (elevated natural killer (NK) cells and neutrophils, and reduced CD4+/CD8+ ratio
      and CD19+ lymphocytes) were found in the control group owing to the time effect
      (p < 0.05). Moreover, a condition * time interaction effect was observed for the
      absolute count of CD3+ (F = 4.26, p < 0.05) and CD3+CD8+ T lymphocytes (F = 4.27,
      p < 0.05), which were elevated following acute glutamine intervention. While a
      potential interaction effect was also observed for the absolute count of CD3+CD4+
      T lymphocytes (F = 3.21, p = 0.08), no condition or interaction effects were
      found for any other outcome measures. The results of this study suggest that
      acute glutamine ingestion evokes CD3+ and CD3+CD8+ T lymphocytosis but does not
      modulate neutrophil and NK cell leukocytosis and immune disturbances after
      exhaustive exercise in the heat.

PMID- 29035688
TI  - Why Social Relationships Are Important for Physical Health: A Systems Approach to
      Understanding and Modifying Risk and Protection.
AB  - Social relationships are adaptive and crucial for survival. This review presents
      existing evidence indicating that our social connections to others have powerful
      influences on health and longevity and that lacking social connection qualifies
      as a risk factor for premature mortality. A systems perspective is presented as a
      framework by which to move social connection into the realm of public health.
      Individuals, and health-relevant biological processes, exist within larger social
      contexts including the family, neighborhood and community, and society and
      culture. Applying the social ecological model, this review highlights the
      interrelationships of individuals within groups in terms of understanding both
      the causal mechanisms by which social connection influences physical health and
      the ways in which this influence can inform potential intervention strategies. A
      systems approach also helps identify gaps in our current understanding that may
      guide future research.

PMID- 29035689
TI  - Principles and Challenges of Applying Epigenetic Epidemiology to Psychology.
AB  - The interplay of genetically driven biological processes and environmental
      factors is a key driver of research questions spanning multiple areas of
      psychology. A nascent area of research focuses on the utility of epigenetic marks
      in capturing this intersection of genes and environment, as epigenetic mechanisms
      are both tightly linked to the genome and environmentally responsive. Advances
      over the past 10 years have allowed large-scale assessment of one epigenetic mark
      in particular, DNA methylation, in human populations, and the examination of DNA
      methylation is becoming increasingly common in psychological studies. In this
      review, we briefly outline some principles of epigenetics, focusing on
      highlighting important considerations unique to DNA methylation studies to guide
      psychologists in incorporating DNA methylation into a project. We discuss study
      design and biological and analytical considerations and conclude by discussing
      interpretability of epigenetic findings and how these important factors are
      currently being applied across areas of psychology.

PMID- 29035690
TI  - The Psychology of Music: Rhythm and Movement.
AB  - The urge to move to music is universal among humans. Unlike visual art, which is
      manifest across space, music is manifest across time. When listeners get carried
      away by the music, either through movement (such as dancing) or through reverie
      (such as trance), it is usually the temporal qualities of the music-its pulse,
      tempo, and rhythmic patterns-that put them in this state. In this article, we
      review studies addressing rhythm, meter, movement, synchronization, entrainment,
      the perception of groove, and other temporal factors that constitute a first step
      to understanding how and why music literally moves us. The experiments we review
      span a range of methodological techniques, including neuroimaging, psychophysics,
      and traditional behavioral experiments, and we also summarize the current studies
      of animal synchronization, engaging an evolutionary perspective on human rhythmic
      perception and cognition.

PMID- 29035692
TI  - Developmental Origins of Chronic Physical Aggression: A Bio-Psycho-Social Model
      for the Next Generation of Preventive Interventions.
AB  - This review describes a bio-psycho-social approach to understanding and
      preventing the development of chronic physical aggression. The debate on the
      developmental origins of aggression has historically opposed genetic and
      environmental mechanisms. Recent studies have shown that the frequency of
      physical aggression peaks in early childhood and then decreases until old age.
      Molecular genetic studies and twin studies have confirmed important genetic
      influences. However, recent epigenetic studies have highlighted the important
      role of environments in gene expression and brain development. These studies
      suggest that interrelated bio-psycho-social channels involved in the development
      of chronic physical aggression are generally the product of an intergenerational
      transmission process occurring through assortative mating, genetic inheritance,
      and the inheritance of physical and social environmental conditions that handicap
      brain functioning and support the use of physical aggression to solve problems.
      Given these intergenerational mechanisms and physical aggression onset in
      infancy, it appears clear that preventive interventions should start early in
      pregnancy, at the latest.

PMID- 29035693
TI  - MMS19 localizes to mitochondria and protects the mitochondrial genome from
      oxidative damage.
AB  - MMS19 localizes to the cytoplasmic and nuclear compartments involved in
      transcription and nucleotide excision repair (NER). However, whether MMS19
      localizes to mitochondria, where it plays a role in maintaining mitochondrial
      genome stability, remains unknown. In this study, we provide the first evidence
      that MMS19 is localized in the inner membrane of mitochondria and participates in
      mtDNA oxidative damage repair. MMS19 knockdown led to mitochondrial dysfunctions
      including decreased mtDNA copy number, diminished mtDNA repair capacity, and
      elevated levels of mtDNA common deletion after oxidative stress.
      Immunoprecipitation - mass spectrometry analysis identified that MMS19 interacts
      with ANT2, a protein associated with mitochondrial ATP metabolism. ANT2 knockdown
      also resulted in a decreased mtDNA repair capacity after oxidative damage. Our
      findings suggest that MMS19 plays an essential role in maintaining mitochondrial
      genome stability.

PMID- 29035691
TI  - How We Hear: The Perception and Neural Coding of Sound.
AB  - Auditory perception is our main gateway to communication with others via speech
      and music, and it also plays an important role in alerting and orienting us to
      new events. This review provides an overview of selected topics pertaining to the
      perception and neural coding of sound, starting with the first stage of filtering
      in the cochlea and its profound impact on perception. The next topic, pitch, has
      been debated for millennia, but recent technical and theoretical developments
      continue to provide us with new insights. Cochlear filtering and pitch both play
      key roles in our ability to parse the auditory scene, enabling us to attend to
      one auditory object or stream while ignoring others. An improved understanding of
      the basic mechanisms of auditory perception will aid us in the quest to tackle
      the increasingly important problem of hearing loss in our aging population.

PMID- 29035694
TI  - Novel Zirconia Materials in Dentistry.
AB  - Zirconias, the strongest of the dental ceramics, are increasingly being
      fabricated in monolithic form for a range of clinical applications. Y-TZP (yttria
      stabilized tetragonal zirconia polycrystal) is the most widely used variant.
      However, current Y-TZP ceramics on the market lack the aesthetics of competitive
      glass-ceramics and are therefore somewhat restricted in the anterior region. This
      article reviews the progressive development of currently available and next
      generation zirconias, representing a concerted drive toward greater translucency
      while preserving adequate strength and toughness. Limitations of efforts directed
      toward this end are examined, such as reducing the content of light-scattering
      alumina sintering aid or incorporating a component of optically isotropic cubic
      phase into the tetragonal structure. The latest fabrication routes based on
      refined starting powders and dopants, with innovative sintering protocols and
      associated surface treatments, are described. The need to understand the several,
      often complex, mechanisms of long-term failure in relation to routine laboratory
      test data is presented as a vital step in bridging the gaps among material
      scientist, dental manufacturer, and clinical provider.

PMID- 29035695
TI  - Expression of macrophage genes within skeletal muscle correlates inversely with
      adiposity and insulin resistance in humans.
AB  - Local inflammation in obese adipose tissue has been shown to contribute to
      insulin resistance; however, the role of macrophage infiltration within skeletal
      muscle is still debatable. This study aimed to evaluate the association of
      skeletal muscle macrophage gene expression with adiposity levels and insulin
      sensitivity in obese patients. Twenty-two nondiabetic obese patients and 23
      healthy lean controls were included. Obese patients underwent a 3-month weight
      loss intervention. Macrophage gene expression in skeletal muscle (quantitative
      real-time polymerase chain reaction), body composition (dual-energy X-ray
      absorptiometry), and insulin sensitivity (homeostatic model assessment (HOMA) and
      oral glucose tolerance test) were compared between groups and their associations
      were analyzed. To validate skeletal muscle findings, we repeated the analyses
      with macrophage gene expression in adipose tissue. Expression levels of
      macrophage genes (CD68, CD11b, CD206, CD16, CD40, and CD163) were lower in
      skeletal muscle tissue of obese versus lean participants. Macrophage gene
      expression was also found to be inversely associated with adiposity, fasting
      insulin, and HOMA (r = -0.4 ~ -0.6, p < 0.05), as well as positively associated
      with insulin sensitivity (r = 0.4 ~ 0.8, p < 0.05). On the other hand, adipose
      tissue macrophage gene expression showed higher levels in obese versus lean
      participants, presenting a positive association with adiposity levels. Macrophage
      gene expression, in both skeletal and adipose tissue samples, was only minimally
      affected by the weight loss intervention. In contrast with the established
      positive relationship between adiposity and macrophage gene expression, an
      unexpected inverse correlation between these 2 variables was observed in skeletal
      muscle tissue. Additionally, muscle macrophage gene expression was inversely
      correlated with insulin resistance.

PMID- 29035696
TI  - The Reliability of Surgical Apgar Score in Predicting Immediate and Late
      Postoperative Morbidity and Mortality: A Narrative Review.
AB  - Surgical Apgar Score is a simple, 10-point scoring system in which a low score
      reliably identifies those patients at risk for adverse perioperative outcomes.
      Surgical techniques and anesthesia management should be directed in such a way
      that the Surgical Apgar Score remains higher to avoid postoperative morbidity and
      mortality.

PMID- 29035698
TI  - Denosumab as a Treatment Alternative for Central Giant Cell Granuloma: A Long
      Term Retrospective Cohort Study.
AB  - PURPOSE: Giant cell granuloma (GCG) of the jaw is a rare disease with high
      morbidity. Various treatment options have been discussed in the past. Since 2010,
      a pharmaceutical therapy with denosumab seems to have been successful for giant
      cell tumors of the femur. The authors hypothesized the equally successful use of
      denosumab for GCGs of the jaws. MATERIALS AND METHODS: In the present
      retrospective cohort study, 5 patients with large GCGs of the jaws were treated
      with denosumab with a follow-up of 25 to 49 months. Frequent clinical follow-ups
      and a radiologic follow-up were performed and systematically analyzed. RESULTS:
      All patients showed a curative treatment response and complete metabolic
      resolution of the GCGs under treatment with denosumab. CONCLUSION: A brief review
      of the relevant literature and a detailed evaluation of current cases led to the
      conclusion that denosumab therapy should be considered a therapeutic option for
      large central GCGs of the jaws. The results of this study suggest denosumab is a
      successful treatment option. A treatment length no shorter than 12 months is
      recommended and monitoring of treatment response can be well managed by positron
      emission tomographic computed tomography or magnetic resonance imaging.

PMID- 29035699
TI  - Risk Factors for Complications of Intraoral Removal of Submandibular Sialoliths.
AB  - PURPOSE: Intraoral removal of submandibular sialoliths is a surgical technique
      for the treatment of sialolithiasis and is reported to have excellent outcomes.
      The aim of this study was to determine the risk factors leading to complications
      of this procedure. PATIENTS AND METHODS: The medical records of 200 patients who
      had undergone intraoral removal of sialoliths from January 2006 through June 2015
      were retrospectively reviewed. A telephone survey was used to check postoperative
      symptoms. Dry mouth, wound infection, lingual nerve dysfunction, and recurrence
      were considered complications. Computed tomograms of the neck were reviewed for
      location, shape, number, and size of the stone. RESULTS: Forty-four patients
      reported a complication. The incidence of complications was significantly higher
      in patients with stones in the proximal region of the salivary duct (proximal
      group) than in those with middle or distally located stones (middle/distal group;
      P < .05). The average stone size was larger in the proximal group; the operation
      time and length of admission also were longer in the proximal group, with a
      statistically significant difference (P < .05). Complaints of lingual nerve
      dysfunction were significantly higher in the proximal group than in the
      middle/distal group (P < .05). CONCLUSION: Patients with proximally located
      stones had more complications, especially lingual nerve dysfunction, than those
      with middle or distally located stones. The former group also required a longer
      operation time and hospital stay.

PMID- 29035697
TI  - Subterranean mammals show convergent regression in ocular genes and enhancers,
      along with adaptation to tunneling.
AB  - The underground environment imposes unique demands on life that have led
      subterranean species to evolve specialized traits, many of which evolved
      convergently. We studied convergence in evolutionary rate in subterranean mammals
      in order to associate phenotypic evolution with specific genetic regions. We
      identified a strong excess of vision- and skin-related genes that changed at
      accelerated rates in the subterranean environment due to relaxed constraint and
      adaptive evolution. We also demonstrate that ocular-specific transcriptional
      enhancers were convergently accelerated, whereas enhancers active outside the eye
      were not. Furthermore, several uncharacterized genes and regulatory sequences
      demonstrated convergence and thus constitute novel candidate sequences for
      congenital ocular disorders. The strong evidence of convergence in these species
      indicates that evolution in this environment is recurrent and predictable and can
      be used to gain insights into phenotype-genotype relationships.

PMID- 29035702
TI  - Editorial Comment.

PMID- 29035701
TI  - Does SOFA predict outcomes better than SIRS in Brazilian ICU patients with
      suspected infection? A retrospective cohort study.
AB  - We compared the discriminatory capacity of the sequential organ failure
      assessment (SOFA) versus the systemic inflammatory response syndrome (SIRS) score
      for predicting ICU mortality, need for and length of mechanical ventilation, ICU
      stay, and hospitalization in patients with suspected infection admitted to a
      mixed Brazilian ICU. We performed a retrospective analysis of a longitudinal ICU
      database from a tertiary hospital in Southern Brazil. Patients were categorized
      according to whether they met the criteria for sepsis according to SOFA
      (variation >=2 points over the baseline clinical condition) and SIRS (SIRS score
      >=2 points). From January 2008 to December 2014, 1487 patients were admitted to
      the ICU due to suspected infection. SOFA >=2 identified more septic patients than
      SIRS >=2 (79.0% [n=1175] vs. 68.5% [n=1020], p<0.001). There was no difference
      between the two scores in predicting ICU mortality (area under the receiver
      operating characteristic curve (AUROC)=0.64 vs. 0.64, p=0.99). SOFA >=2 was
      marginally better than SIRS >=2 in predicting need for mechanical ventilation
      (AUROC=0.64 vs. 0.62, p=0.001), ICU stay>7 days (AUROC=0.65 vs. 0.63, p=0.004),
      and length of hospitalization >10 days (AUROC=0.61 vs. 0.59, p<0.001). There was
      no difference between the two scores in predicting mechanical ventilation >7
      days.

PMID- 29035703
TI  - A randomized clinical trial examining the effects of an anxiety sensitivity
      intervention on insomnia symptoms: Replication and extension.
AB  - Insomnia disorder is impairing and prevalent, particularly among individuals with
      comorbid anxiety disorders. Despite the availability of effective computerized
      treatments for insomnia, there are few that target both insomnia as well as co
      occurring anxiety symptoms. The current study tests the efficacy of a
      computerized treatment for anxiety sensitivity cognitive concerns, a
      transdiagnostic risk factor for anxiety, mood, and insomnia symptoms, against a
      repeated contact control, on reducing insomnia symptoms. Hypotheses were tested
      in a mixed clinical sample of community individuals presenting for a treatment
      study (n = 151) who were followed up 1-, 3- and 6-months after treatment. Results
      indicated that the anxiety sensitivity intervention resulted in reductions in
      insomnia symptoms and clinically significant insomnia scores at 3- and 6-month
      follow-ups. These reductions remained significant when covarying for concurrent
      reductions in depression and anxiety. Models accounted for 15-54% of the variance
      in follow-up insomnia symptoms. Current findings add to a growing body of
      literature suggesting anxiety sensitivity may play a causal role in insomnia
      symptoms. Results also suggest that targeting anxiety sensitivity may be an
      effective way to reduce insomnia symptoms in a brief and portable intervention
      that also reduces symptoms commonly comorbid with insomnia disorder.

PMID- 29035704
TI  - Anesthetic management of a patient with benign tracheal tumor identified at
      induction of general anesthesia.

PMID- 29035705
TI  - Linking patients with buprenorphine treatment in primary care: Predictors of
      engagement.
AB  - BACKGROUND: Office-based buprenorphine treatment promises to expand effective
      treatment for opioid use disorder. Unfortunately, patients may be lost during
      engagement, before induction with medication. Few data are available regarding
      rates and predictors of successfully reaching induction. METHODS: The sample
      included 100 consecutive patients seeking treatment in 2016 at an office-based
      buprenorphine treatment program in an urban, academic primary care clinic.
      Patients completed phone intake, nurse visit and physician visit prior to
      induction. We reviewed electronic medical records to describe the time to
      complete each step and used multivariable logistic regression to identify
      predictors of reaching induction. RESULTS: Sixty percent of the sample dropped
      out prior to induction, with the majority dropping out prior to the nurse visit.
      For patients who successfully completed induction, median time between screening
      and induction was 18days (interquartile range 13-30days). After adjustment for
      other factors, completing induction was significantly less likely in patients
      with recent polysubstance use (OR=0.15, 95% CI=0.04-0.53), prior methadone
      treatment (OR=0.05, 95% CI=0.01-0.36), prior buprenorphine treatment (OR=0.60,
      95% CI=0.01-0.47), or other prior treatment (OR=0.19, 95% CI=0.04-0.98).
      Sociodemographic characteristics, such as younger age, minority race/ethnicity,
      homelessness, unemployment, history of incarceration and relationship status were
      not significant predictors. CONCLUSIONS: Over half of patients beginning primary
      care buprenorphine treatment were not successful in starting medication. Those
      with polysubstance use or previous substance use treatment were least likely to
      be successful. Programs should carefully consider barriers that might prevent
      treatment-seeking patients from starting medications. Some patients might need
      enhanced support to successfully start treatment with buprenorphine.

PMID- 29035706
TI  - Serious suicide attempts in outpatients with multiple substance use disorders.
AB  - BACKGROUND: Suicide is a major public health concern and suicide attempts (SA)
      are frequent and burdensome in people suffering from substance use disorders
      (SUDs). In particular, serious SAs are a preoccupying form of attempt, which
      remain largely overlooked in these populations, especially regarding basic risk
      factors such as gender, addictive comorbidity and substance use patterns. Thus,
      we undertook a gender-specific approach to identify the risk factors for serious
      SAs in outpatients with multiple SUDs. MATERIAL AND METHODS: 433 Treatment
      seeking outpatients were consecutively recruited in specialized care centers and
      reliably classified as serious, non-serious and non-suicide attempters. We also
      characterized lifetime exposure to SUDs, including tobacco smoking, with
      standardized instruments. Current medication, including psychotropic treatments
      were collected, which informed psychiatric diagnoses. Multinomial regression
      identified independent factors specifically associated with serious SAs in each
      gender, separately. RESULTS: 32% Participants (N=139, 47% Women and 27% Men)
      reported lifetime SA. There were 82 serious attempters (59% of attempters),
      without significant gender difference. Sedative dependence was an independent
      risk factor for serious SA compared to non-SA in Women and compared to non
      serious SA in Men, respectively. Other risk factors included later onset of daily
      tobacco smoking in Men and history of psychiatric hospitalizations in Women,
      whose serious SA risk was conversely lower when reporting opiate use disorder or
      mood disorder, probably because of treatment issues. CONCLUSIONS: Despite several
      study limitations, we identified subgroups for a better-tailored prevention of
      serious SAs among individuals with SUDs, notably highlighting the need to better
      prevent and treat sedative dependence.

PMID- 29035707
TI  - Clinician identification of elevated symptoms of depression among individuals
      seeking treatment for substance misuse.
AB  - BACKGROUND: Depression is common among those experiencing alcohol and other drug
      (AOD) disorders. It has been suggested that identifying depressive symptoms among
      this group is important for case management. Despite this, there is a lack of
      research examining how well clinicians perform this task within this setting.
      AIMS: To determine the: (i) accuracy of clinician identified elevated symptoms of
      depression among clients seeking treatment for AOD misuse as compared to a
      standardized self-report psychiatric screening tool; and (ii) clinician and
      client characteristics associated with accurate identification of elevated
      symptoms of depression. METHODS: The study used a descriptive cohort design.
      Participants from two Australian AOD outpatient clinics reported demographic data
      and completed the Patient Health Questionnaire (PHQ-9) to identify elevated
      symptoms of depression. Clinicians were asked to indicate the presence or absence
      of depression for individual clients. Client and clinician data were compared.
      RESULTS: Sensitivity of clinician identified elevated symptoms of depression,
      compared with the PHQ-9, was moderate at 73.0% (95% CI=63.7, 81.0) and
      specificity was low with 49.5% (95% CI=39.9, 61.2) accurately identified as not
      having elevated symptoms of depression. AOD clinicians' years' of experience,
      clients' main substance and length of treatment were associated with accuracy of
      identification. CONCLUSION: Clinicians identify elevated symptoms of depression
      with moderate accuracy amongst individuals with AOD disorders. There is a
      tendency to over-identify which may contribute to inaccuracies. Routine screening
      may assist in improving identification of depressive symptoms and place greater
      focus on mental health comorbidities.

PMID- 29035708
TI  - An assessment of the utilization of the preclinical rodent model literature in
      clinical trials of putative therapeutics for the treatment of alcohol use
      disorders.
AB  - OBJECTIVE: Rodent models of Alcohol Use Disorders (AUD) are used extensively by
      preclinical researchers to develop new therapeutics for the treatment of AUD.
      Although these models play an important role in the development of novel,
      targeted therapeutics, their role in bringing therapeutics to clinical trials is
      unclear, as off-label use of existing medications not approved for the treatment
      of AUD is commonly seen in the clinic and clinical trials. METHOD: In the current
      study, we used the Clinicaltrials.gov database to obtain a list of drugs that
      have been tested for efficacy in a clinical trial between 1997 and 2017. We then
      conducted a set of literature searches to determine which of the 98 unique drugs
      we identified had shown efficacy in a rodent model of an AUD prior to being
      tested in a clinical trial. RESULTS: We found that slightly less than half of the
      drugs tested in clinical trials (48%) had shown prior efficacy in any rodent
      model of an AUD, while the remaining 52% of drugs were used off-label, or in some
      cases, following non-published studies. CONCLUSION: This study raises the
      question of how clinical researchers incorporate results from preclinical studies
      in the decision to bring a drug to a clinical trial. Our results underscore the
      need for ongoing communication among preclinical and clinical researchers.

PMID- 29035709
TI  - Heart rate variability and salivary cortisol in very preterm children during
      school age.
AB  - The autonomic nervous system (ANS) plays a major role in the human stress
      response and reflects physical and psychological adaptability to a changing
      environment. Long-term exposure to early life stressors may alter the function of
      the ANS. The present study examines differences in the ANS between children born
      very preterm and full-term as well as the association between the ANS and the
      hypothalamic-pituitary-adrenal (HPA) axis, the other main branch of the human
      stress system. Fifty-four healthy children born very preterm (<32nd gestational
      week) and 67 full-term children aged 7-12 years provided data for the present
      study. Polysomnography (PSG) assessments were obtained during a night at the
      children's home in lying position at rest (wake) and during different sleep
      stages (stage 2 sleep, slow wave sleep, rapid-eye-movement sleep). Autonomic
      function was assessed by use of heart rate variability, specifically low
      frequency power (LF), high frequency power (HF), total spectral power (Tot Pow),
      and the LF/HF ratio. HPA axis activity was measured using salivary cortisol the
      next morning at awakening, 10, 20, and 30min later. Children born very preterm
      had lower LF/HF ratio during wake and stage 2 sleep compared to full-term
      children. Moreover, higher LF, Tot Pow, and LF/HF ratio during wake, stage 2
      sleep, and REM sleep were related to more post-awakening cortisol secretion. The
      present study provides evidence on long-term ANS alterations after very preterm
      birth. Moreover, findings suggest a relation between the ANS and the HPA axis and
      therefore support the notion of mutual feedback between the two human stress
      systems.

PMID- 29035710
TI  - Blunted basal corticosterone pulsatility predicts post-exposure susceptibility to
      PTSD phenotype in rats.
AB  - The basal activity of the hypothalamic-pituitary-adrenal axis is highly dynamic
      and is characterized by both circadian and ultradian (pulsatile) patterns of
      hormone secretion. Pulsatility of glucocorticoids has been determined to be
      critical for optimal transcriptional, neuroendocrine, and behavioral responses.
      We used an animal model of post-traumatic stress disorder (PTSD) to assess
      whether stress-induced impairment of behavioral responses is correlated with
      aberrant secretion of corticosterone. Serial blood samples were collected
      manually via the jugular vein cannula during the light-(inactive)-phase in
      conscious male rats at 20-min intervals for a period of 5h before and 6.5h after
      exposure to predator scent stress. The outcome measures included behavior in an
      elevated plus-maze and acoustic startle response 7days after exposure. Individual
      animals were retrospectively classified as having "extreme", "partial", or
      "minimal" behavioral responses according to pre-set cut-off criteria for
      behavioral response patterns. Corticosterone secretion patterns were analyzed
      retrospectively. Under basal conditions, the amplitude of ultradian oscillations
      of corticosterone levels, rather than the mean corticosterone level or the
      frequency of corticosterone pulsatility, was significantly reduced in individuals
      who displayed PTSD-phenotype 8days later. In addition, extreme disruption of
      behavior on day 8 post-exposure was also characterized by a blunting of
      corticosterone response to the stressor. Animals with behavior that was only
      partially affected or unaffected displayed none of the above changes. Blunted
      basal corticosterone pulse amplitude is a pre-existing susceptibility or risk
      factor for PTSD, which originates from prior (life) experiences and may therefore
      predict post-exposure PTSD-phenotype in rats.

PMID- 29035712
TI  - Process integration for material synthesis from a deactivated catalyst: Studies
      on the interaction of metal ions between two immiscible phases.
AB  - Present investigation deals with the treatment of deactivated Co-Mn bromide
      catalyst for the recovery of Co and Mn as Co metal powder and chemical manganese
      dioxide by an integrated process comprising of a selective metal ion transfer
      from an aqueous solution containing a mixture of metal ions with a saponified
      solution of di-2ethyl-hexyl phosphoric acid, followed by selective scrubbing and
      metal stripping. The pure metal solutions so obtained were subjected to
      precipitation and hydrothermal treatment to obtain a desired material. The
      deactivated catalyst was leached by H2SO4 in presence of H2O2 followed by
      removing Fe, Si etc. The purified leach liquor of composition: 6.9g/L Co, 9.4g/L
      Mn was used for detail study to optimize the best conditions for the separation
      of Co from Mn. Experimental observations show that the extraction of both
      increased with increasing equilibrium pH and the concentration of the organic,
      with a separation factor of about 10, at equilibrium pH of 3. A quantitative
      extraction of Mn was possible with 20% D2EHPA in three stage counter-current
      extraction. After Co scrubbing, Mn was stripped with dilute H2SO4 and high pure
      spherical shaped CMD was produced. Co in the raffinate was recovered as powder by
      hydrothermal H2- reduction.

PMID- 29035713
TI  - An overview of chemical additives present in plastics: Migration, release, fate
      and environmental impact during their use, disposal and recycling.
AB  - Over the last 60 years plastics production has increased manifold, owing to their
      inexpensive, multipurpose, durable and lightweight nature. These characteristics
      have raised the demand for plastic materials that will continue to grow over the
      coming years. However, with increased plastic materials production, comes
      increased plastic material wastage creating a number of challenges, as well as
      opportunities to the waste management industry. The present overview highlights
      the waste management and pollution challenges, emphasising on the various
      chemical substances (known as "additives") contained in all plastic products for
      enhancing polymer properties and prolonging their life. Despite how useful these
      additives are in the functionality of polymer products, their potential to
      contaminate soil, air, water and food is widely documented in literature and
      described herein. These additives can potentially migrate and undesirably lead to
      human exposure via e.g. food contact materials, such as packaging. They can,
      also, be released from plastics during the various recycling and recovery
      processes and from the products produced from recyclates. Thus, sound recycling
      has to be performed in such a way as to ensure that emission of substances of
      high concern and contamination of recycled products is avoided, ensuring
      environmental and human health protection, at all times.

PMID- 29035711
TI  - Childhood adversity, social support, and telomere length among perinatal women.
AB  - Adverse perinatal health outcomes are heightened among women with psychosocial
      risk factors, including childhood adversity and a lack of social support.
      Biological aging could be one pathway by which such outcomes occur. However, data
      examining links between psychosocial factors and indicators of biological aging
      among perinatal women are limited. The current study examined the associations of
      childhood socioeconomic status (SES), childhood trauma, and current social
      support with telomere length in peripheral blood mononuclear cells (PBMCs) in a
      sample of 81 women assessed in early, mid, and late pregnancy as well as 7-11
      weeks postpartum. Childhood SES was defined as perceived childhood social class
      and parental educational attainment. Measures included the Childhood Trauma
      Questionnaire, Center for Epidemiologic Studies-Depression Scale,
      Multidimensional Scale of Perceived Social Support, and average telomere length
      in PBMCs. Per a linear mixed model, telomere length did not change across
      pregnancy and postpartum visits; thus, subsequent analyses defined telomere
      length as the average across all available timepoints. ANCOVAs showed group
      differences by perceived childhood social class, maternal and paternal
      educational attainment, and current family social support, with lower values
      corresponding with shorter telomeres, after adjustment for possible confounds. No
      effects of childhood trauma or social support from significant others or friends
      on telomere length were observed. Findings demonstrate that while current SES was
      not related to telomeres, low childhood SES, independent of current SES, and low
      family social support were distinct risk factors for cellular aging in women.
      These data have relevance for understanding potential mechanisms by which early
      life deprivation of socioeconomic and relationship resources affect maternal
      health. In turn, this has potential significance for intergenerational
      transmission of telomere length. The predictive value of markers of biological
      versus chronological age on birth outcomes warrants investigation.

PMID- 29035714
TI  - Biodegradation of triclosan in diatom Navicula sp.: Kinetics, transformation
      products, toxicity evaluation and the effects of pH and potassium permanganate.
AB  - Triclosan (TCS) is one of the most widely used pharmaceutically active compounds
      and frequently detected in treated wastewater and the impacted aquatic
      environment. However, the fate and toxicity of TCS in aquatic organisms is poorly
      known, including in particular the potential for the formation of incomplete
      biological transformation products. In this study, TCS posed high toxic effects
      (e.g., growth inhibition and damage of photosynthesis) to typical freshwater
      diatom Navicula sp., with the 24h and 72h EC50 values of 173.3 and 145.6MUgL-1,
      respectively. The bioaccumulation of TCS in diatom cells increased with the
      increasing exposure to TCS and showed to be time-dependent. The higher
      intracellular TCS lead to higher toxicity on Navicula sp. The intracellular TCS
      concentration and the growth inhibition of TCS in Navicula sp. at pH 7.5 was
      obviously higher than that at pH 8.3, which was likely due to the higher
      abundance of unionized TCS in the culture. KMnO4 reduced both bioaccumulation and
      toxicity of TCS in Navicula sp., especially at pH 8.3. A total of seven products
      were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). These
      findings will provide a reference for the risk assessment of TCS in aquatic
      environment.

PMID- 29035715
TI  - Linear and crosslinked Polyurethanes based catalysts for reduction of methylene
      blue.
AB  - The large amount of synthetic dyes in effluents is a serious concern to be
      addressed. The chemical reduction is one of the potential way to resolve this
      problem. In this study, linear and crosslinked polyurethanes i.e. LPUR & CLPUR
      were synthesized from toluene diisocyanate (TDI), polyethylene glycol
      (PEG;1000g/mole) and tetraethylenepentamine (TEPA). The structure and morphology
      of synthesized materials were examined by FTIR, SEM and BET. The CLPUR was found
      stable in aqueous system with 0.80g/cm3 density and 16.4998m2g-1 surface area.
      These materials were applied for the reduction of methylene blue in presence of
      NaBH4. Both, polymers catalyzed the process and showed 100% reduction in 16 and
      28mins., respectively, while, the reduction rate was significantly low in absence
      of these materials, even after 120mins. Furthermore, negligible adsorption was
      observed with only 7% removal of dye. The best reduction rates were observed at
      low concentration of dye, increasing concentration of NaBH4 and with more dosage
      of polymeric catalyst. The kinetic study of process followed zero order kinetics.
      It was hence concluded that both synthesized polymers played a catalytic role in
      reduction process. However, stability in aqueous system and better efficiency in
      reduction process endorsed CLPUR as an optimal choice for further studies.

PMID- 29035716
TI  - Synthesis, photophysical and cellular characterisation of folate and methotrexate
      labelled luminescent lanthanide complexes.
AB  - In this work we have developed a series of highly emissive europium(III) and
      terbium(III) complexes tethered to either folic acid (FA) or methotrexate (MTX),
      with the aim of developing visual probes that enable the imaging of folate
      receptors in cancer cells. The synthesis, photophysical properties and cellular
      behaviour are reported for four new lanthanide Ln(III) complexes, where either FA
      or MTX are tethered to 1,4,7-tris(carbonylmethyl)-10-(4'-quinolineacetic acid,
      (7'-acetamido)-1',2'-dihydro-2'-oxo)-1,4,7,10-tetraazacyclododecane Ln(III)
      complex, and Ln(III)=Eu(III) or Tb(III); herein referred to as Eu-FA, Eu-MTX, Tb
      FA or Tb-MTX. All four complexes were found to be sensitive to the presence of
      the folate receptor in a range of cell lines. The MTX conjugates showed different
      cellular specificity in an oral adenosquamous carcinoma cell line (CAL-27)
      compared with the analogous FA conjugates. This suggests that it is viable to
      explore differences in folate receptors using folate vs. anti-folate probes, with
      labels that have different emissive properties (e.g. Eu-FA vs. Tb-MTX). The MTX
      complexes were found to be the most cytotoxic, with Eu-MTX showing greater
      cytotoxicity than free MTX or the isostructural Tb-MTX. This suggested that there
      could be a synergistic effect on toxicity for the Eu(III) chelate and the MTX
      components of the complex.

PMID- 29035717
TI  - Concordance of health states in couples: Analysis of self-reported, nurse
      administered and blood-based biomarker data in the UK Understanding Society
      panel.
AB  - We use self-reported health measures, nurse-administered measurements and blood
      based biomarkers to examine the concordance between health states of partners in
      marital/cohabiting relationships in the UK. A model of cumulative health
      exposures is used to interpret the empirical pattern of between-partner health
      correlation in relation to elapsed relationship duration, allowing us to
      distinguish non-causal correlation due to assortative mating from potentially
      causal effects of shared lifestyle and environmental factors. We find important
      differences between the results for different health indicators, with strongest
      homogamy correlations observed for adiposity, followed by blood pressure, heart
      rate, inflammatory markers and cholesterol, and also self-assessed general health
      and functional difficulties. We find no evidence of a "dose-response
      relationship" for marriage duration, and show that this suggests - perhaps
      counterintuitively - that shared lifestyle factors and homogamous partner
      selection make roughly equal contributions to the concordance we observe in most
      of the health measures we examine.

PMID- 29035718
TI  - Assessment of the coding accuracy of warfarin-related bleeding events.
AB  - INTRODUCTION: Using International Classification of Diseases, 9th edition (ICD-9)
      diagnosis codes to identify potential warfarin-related bleeding events from
      administrative datasets is highly efficient but may be prone to identifying non
      events. The objective of this study was to evaluate the ability of bleeding
      related ICD-9 codes to identify true bleeding events in patients who were
      receiving warfarin therapy at the time of hospitalization. METHODS: This was a
      cross-sectional study conducted in an integrated healthcare delivery system.
      Anticoagulated patients aged >=18years and hospitalized between January 1, 2014
      and March 31, 2014 were identified using administrative data queries. All
      hospitalizations were manually chart reviewed by a trained abstractor blinded to
      hospitalization diagnoses to assess for true bleeding events. Identification of
      the presence or lack of bleeding-related ICD-9 diagnosis code(s) for each
      hospitalization was then performed. Sensitivity, specificity, positive predictive
      value (PPV), and negative predictive value (NPV) were calculated for each ICD-9
      code present. RESULTS: There were 486 hospitalizations in 468 anticoagulated
      patients with 57 true bleeding events identified. Patients had a mean age of
      73.4years and 50% were female. For codes in the principal position, sensitivity,
      specificity, PPV, and NPV were 7.0%, 99.8%, 80.0%, and 89.0%, respectively. For
      codes in any position, sensitivity, specificity, PPV, and NPV were 94.7%, 90.9%,
      58.1%, and 99.2%, respectively. For major bleeding, sensitivity, specificity,
      PPV, and NPV were 100%, 83.1%, 14.0%, and 100%, respectively. CONCLUSIONS: While
      the absence of a bleeding ICD-9 code reliably ruled-out hospitalization for
      warfarin-related bleeding, bleeding ICD-9 codes in the principal position were
      rarely used and undesirable false positive rates were identified when ICD-9 codes
      when recorded in any position and for major bleeding. Manual chart review is
      recommended to validate bleeding events from administrative data.

PMID- 29035719
TI  - Recent advancements in the mitigation of obnoxious nitrogenous gases.
AB  - Nitrogenous gaseous emissions commonly have an obnoxious odor associated with it,
      which when discharged into the environment results in serious environmental
      problems and health hazards. Several strategies for mitigation of nitrogenous
      odorants have been reported which include physical, chemical and biological
      methods. Biological treatments are widely employed because of their efficiency
      even at low concentration, where physical and chemical methods are not effective.
      Most commonly used biological treatment methods are biofiltration, biotrickling
      filters and membrane bioreactors with innovative reactor design, mixing pattern,
      and air sparging, for example FEBR, ALR, etc. These treatment methods require a
      critical assessment for the mitigation of obnoxious nitrogen emissions,
      especially in the context of environmental protection. This review offers a
      critical evaluation of treatment methods for the mitigation of nitrogenous
      odorous compound with a key emphasis on biological treatment systems. Also,
      various mathematical modelling techniques required for optimized operation of
      biotreatment systems has been discussed.

PMID- 29035720
TI  - An internationally standardized species identification test for use on suspected
      seized rhinoceros horn in the illegal wildlife trade.
AB  - Rhinoceros (rhino) numbers have dwindled substantially over the past century. As
      a result, three of the five species are now considered to be critically
      endangered, one species is vulnerable and one species is near-threatened.
      Poaching has increased dramatically over the past decade due to a growing demand
      for rhino horn products, primarily in Asia. Improved wildlife forensic
      techniques, such as validated tests for species identification of seized horns,
      are critical to aid current enforcement and prosecution efforts and provide a
      deterrent to future rhino horn trafficking. Here, we present an internationally
      standardized species identification test based on a 230 base pair cytochrome-b
      region. This test improves on previous nested PCR protocols and can be used for
      the discrimination of samples with <20pg of template DNA, thus suitable for DNA
      extracted from horn products. The assay was designed to amplify water buffalo
      samples, a common 'rhino horn' substitute, but to exclude human DNA, a common
      contaminant. Phylogenetic analyses using this partial cytochrome-b region
      resolved the five extant rhino species. Testing successfully returned a sequence
      and correct identification for all of the known rhino horn samples and vouchered
      rhino samples from museum and zoo collections, and provided species level
      identification for 47 out of 52 unknown samples from seizures. Validation and
      standardization was carried out across five different laboratories, in four
      different countries, demonstrating it to be an effective and reproducible test,
      robust to inter laboratory variation in equipment and consumables (such as PCR
      reagents). This is one of the first species identification tests to be
      internationally standardized to produce data for evidential proceedings and the
      first published validated test for rhinos, one of the flagship species groups of
      the illegal wildlife trade and for which forensic tools are urgently required.
      This study serves as a model for how species identification tests should be
      standardized and disseminated for wildlife forensic testing.

PMID- 29035721
TI  - Cdc42 is essential for the polarized movement and adhesion of human dental pulp
      stem cells.
AB  - OBJECTIVE: Stem cell-based tissue repair and regeneration require the regulation
      of cell migration and adhesion. As a regulator of cell polarization, Cdc42 (cell
      division control protein 42) plays a basic role at the initial stage of cell
      migration and adhesion. This study explores the effect of Cdc42 on the polarized
      migration and adhesion of hDPSCs (human dental pulp stem cells). DESIGN: HDPSCs
      were isolated from extracted third molars and transfected with siRNA targeted
      against Cdc42. Scratch wound assays and transwell assays were performed to detect
      the migration of human dental pulp stem cells. Polarization assays were applied
      to explore the polarized movement of Golgi bodies and nuclei. Western blot was
      used to examine the expression of related proteins. RESULTS: The expression of
      Cdc42 was knocked down by siRNA transfection, which inhibited the migration of
      hDPSCs in both the scratch wound assays and transwell assays. Meanwhile, the
      proportion of polarized hDPSCs during migration was also decreased, and the
      adhesion ability of hDPSCs was downregulated. Western blot demonstrated that
      these effects were dependent on FAK (focal adhesion kinase), beta-catenin and
      GSK3beta (Glycogen synthase kinase-3beta). CONCLUSION: Our study demonstrates
      that Cdc42 plays an essential role during the polarized movement and adhesion of
      hDPSCs.

PMID- 29035722
TI  - Multiple complex somatosensory systems in mature rat molars defined by
      immunohistochemistry.
AB  - OBJECTIVE: Intradental sensory receptors trigger painful sensations and
      unperceived mechanosensitivity, but the receptor bases for those functions are
      only partly defined. We present new evidence here concerning complex endings of
      myelinated axons in rat molars. DESIGN: We sectioned mature rat jaws in sagittal
      and transverse planes to analyze neural immunoreactivity (IR) for parvalbumin,
      peripherin, neurofilament protein, neurotrophin receptors, synaptophysin,
      calcitonin gene-related peptide (CGRP), or mas-related g-protein-receptor-d
      (Mrgprd). RESULTS: We found two complex sensory systems in mature rat molar
      dentin that labeled with neurofilament protein-IR, plus either parvalbumin-IR or
      peripherin-IR. The parvalbumin-IR system made extensively branched, beaded
      endings focused into dentin throughout each pulp horn. The peripherin-IR system
      primarily made unbeaded, fork-shaped dentinal endings scattered throughout crown
      including cervical regions. Both of these systems differed from neuropeptide CGRP
      IR. In molar pulp we found peripherin- and parvalbumin-IR layered endings, either
      near special horizontal plexus arrays or in small coiled endings near tangled
      plexus, each with specific foci for specific pulp horns. Parvalbumin-IR nerve
      fibers had Abeta axons (5-7MUm diameter), while peripherin-IR axons were thinner
      Adelta size (2-5MUm). Mechano-nociceptive Mrgprd-IR was only found in peripherin
      IR axons. CONCLUSIONS: Complex somatosensory receptors in rat molars include two
      types of dentinal endings that both differ from CGRP-IR endings, and at least two
      newly defined types of pulpal endings. The PV-IR neurons with their widely
      branched, synaptophysin-rich, intradentinal beaded endings are good candidates
      for endodontic non-nociceptive, low threshold, unperceived mechanoreceptors. The
      complex molar dentinal and pulpal sensory systems were not found in rat incisors.

PMID- 29035723
TI  - Raloxifene reduces the risk of local alveolar bone destruction in a mouse model
      of periodontitis combined with systemic postmenopausal osteoporosis.
AB  - OBJECTIVE: Periodontitis is characterized by local inflammation leading to tooth
      loss and severe destruction of alveolar bone. Raloxifene is a selective estrogen
      receptor modulator (SERM) that halts estrogen deficiency-induced systemic bone
      loss in postmenopausal osteoporosis without the side effects of cancer in breast
      and uterus. In this study, we examined the effects of raloxifene on alveolar bone
      mass in a mouse model with estrogen deficiency-induced periodontitis. METHODS:
      Periodontitis was induced by the injection of lipopolysaccharide (LPS) into the
      lower gingiva in ovariectomized (OVX) mice, and the alveolar bone and femur bone
      mineral density (BMD) were analyzed by dual-energy X-ray absorptiometry. To
      explore the direct osteoclast inhibitory effect of raloxifene, a co-culture
      system for osteoclast formation and organ culture of alveolar bone was
      established. RESULTS: When OVX mice were treated with raloxifene, the bone loss
      in both alveolar bone and femur were abrogated. Interleukin 1 and/or LPS
      stimulated the osteoclast formation and bone-resorbing activity; however,
      raloxifene did not show any inhibitory effect on the osteoclast formation or
      function. In vivo local injection of raloxifene also did not prevent bone
      resorption in a mouse model of periodontitis. However, the systemic treatment of
      raloxifene using a mini-osmotic pump did prevent the loss of BMD of alveolar bone
      induced by LPS. CONCLUSION: These results suggest that the SERM raloxifene
      systemically maintain alveolar bone mass in a mouse model of periodontitis with
      osteoporosis. Increasing the alveolar bone mass by SERMs treatment in patients
      with postmenopausal osteoporosis may be a useful approach to preventing the
      destruction of alveolar bone in late-onset periodontitis.

PMID- 29035724
TI  - Factors associated with post-stroke suicidal death.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to estimate the relative risk
      of suicidal death compared to the general population and to identify risk factors
      for suicidal death among stroke patients. METHODS: Our sample consisted of 7175
      patients who were diagnosed with stroke and admitted at Asan Medical Center from
      January 2005 to December 2012. Information on suicidal death was obtained from
      the database of the Korean National Statistical Office. The standardized
      mortality ratio (SMR) for post-stroke suicide was estimated. Additionally, we
      conducted a 1:6 case-control study using patients who did not commit suicide.
      RESULTS: Thirty patients committed suicidal death, with the mean time interval
      between hospital admission and suicide being 1.9 +/- 1.8 years. The SMR for
      suicide was 2.14 (95% confidence interval [CI], 1.44-3.05). Case-control analysis
      revealed that diabetes mellitus, depression, and large ischemic lesions in the
      subcortex and brainstem were significantly associated with suicidal death.
      CONCLUSIONS: The risk of suicidal death is approximately 2 times higher than that
      in the general population. Depression, diabetes, and large lesions in specific
      locations should be considered in the implementation of suicide prevention
      strategies in stroke patients.

PMID- 29035725
TI  - Alterations to Juvenile Zebrafish (Danio rerio) Swim Performance after Acute
      Embryonic Exposure to Sub-lethal Exposures of Hydraulic Fracturing Flowback and
      Produced Water.
AB  - Hydraulic fracturing flowback and produced water (FPW) is a wastewater produced
      during fracturing activities in an operating well which is hyper saline and
      chemically heterogeneous in nature, containing both anthropogenic and petrogenic
      chemicals. Determination of FPW associated toxicity to embryonic fish is limited,
      while investigation into how embryonic exposures may affect later life stages is
      not yet studied. Zebrafish embryos (24hrs post fertilization) were acutely
      exposed to 2.5% and 5% FPW fractions for either 24 or 48hrs and returned to
      freshwater. After either 24 or 48h exposures, embryos were examined for
      expression of 3 hypoxia related genes. Erythropoietin (epoa) but not hypoxia
      inducible factor (hif1aa) nor hemoglobin -beta chain (hbbe1.1) was up-regulated
      after either 24 or 48h FPW exposure. Surviving embryos were placed in freshwater
      and grown to a juvenile stage (60days post fertilization). Previously exposed
      zebrafish were analyzed for both swim performance (Ucrit and Umax) and aerobic
      capacity. Fish exposed to both sediment containing (FPW-S) or sediment free (FPW
      SF) FPW displayed significantly reduced aerobic scope and Ucrit/Umax values
      compared to control conditions. Our results collectively suggest that organics
      present in our FPW sample may be responsible for sub-lethal fitness and metabolic
      responses. We provide evidence supporting the theory that the cardio-respiratory
      system is impacted by FPW exposure. This is the first known research associating
      embryonic FPW exposures to sub-lethal performance related responses in later life
      fish stages.

PMID- 29035726
TI  - Nonionic surfactants enhanced enzymatic hydrolysis of cellulose by reducing
      cellulase deactivation caused by shear force and air-liquid interface.
AB  - Effects of nonionic surfactants on enzymatic hydrolysis of Avicel at different
      agitation rates and solid loadings and the mechanism were studied. Nonionic
      surfactants couldn't improve the enzymatic hydrolysis efficiency at 0 and 100rpm
      but could enhance the enzymatic hydrolysis significantly at high agitation rate
      (200 and 250rpm). Cellulase was easily deactivated at high agitation rate and the
      addition of nonionic surfactants can protect against the shear-induced
      deactivation, especially when the cellulase concentration was low. When 25mg
      protein/L of cellulase solution was incubated at 200rpm for 72h, the enzyme
      activity increased from 36.0% to 89.5% by adding PEG4600. Moreover nonionic
      surfactants can compete with enzyme in air-liquid interface and reduce the amount
      of enzyme exposed in the air-liquid interface. The mechanism was proposed that
      nonionic surfactants could enhance the enzymatic hydrolysis of Avicel by reducing
      the cellulase deactivation caused by shear force and air-liquid interface.

PMID- 29035727
TI  - Co-pyrolysis characteristics and kinetic analysis of organic food waste and
      plastic.
AB  - In this work, typical organic food waste (soybean protein (SP)) and typical
      chlorine enriched plastic waste (polyvinyl chloride (PVC)) were chosen as
      principal MSW components and their interaction during co-pyrolysis was
      investigated. Results indicate that the interaction accelerated the reaction
      during co-pyrolysis. The activation energies needed were 2-13% lower for the
      decomposition of mixture compared with linear calculation while the maximum
      reaction rates were 12-16% higher than calculation. In the fixed-bed experiments,
      interaction was observed to reduce the yield of tar by 2-69% and promote the
      yield of char by 13-39% compared with linear calculation. In addition, 2-6 times
      more heavy components and 61-93% less nitrogen-containing components were formed
      for tar derived from mixtures.

PMID- 29035728
TI  - Engineering Pediococcus acidilactici with xylose assimilation pathway for high
      titer cellulosic l-lactic acid fermentation.
AB  - Xylose-assimilating pathways were constructed in the parental Pediococcus
      acidilactici strain and evolutionarily adapted to yield a highly stable co
      fermentation strain for l-lactic acid production. The phosphoketolase pathway
      (PK) was blocked for reduction of acetic acid generation by disrupting
      phosphoketolase (pkt) gene. The pentose phosphate pathway (PPP) was reconstructed
      for xylose assimilation by integrating four heterologous genes encoding
      transketolase (tkt), transaldolase (tal), xylose isomerase (xylA) and
      xylulokinase (xylB) into the P. acidilactici chromosome. The xylose-assimilating
      ability of the constructed strain was significantly improved by long term
      adaptive evolution. The engineered strain was applied to the simultaneous
      saccharification and co-fermentation (SSCF) under high solids loading of wheat
      straw. The l-lactic acid titer, productivity and xylose conversion reached the
      record high at 130.8+/-1.6g/L, 1.82+/-0.0g/L/h, and 94.9+/-0.0%, respectively.
      This study provided an important strain and process prototype for production of
      high titer cellulosic l-lactic acid.

PMID- 29035729
TI  - Pre-clinical in vitro infection models.
AB  - Given the current magnitude of the problem of antimicrobial resistance,
      particularly in the hospital setting, getting new agents to patients at the right
      dose and schedule is incredibly important. In vitro systems such as the 1
      compartment model and the hollow fiber infection model (HFIM) can provide
      valuable information that allows rational decisions to be made which will drive
      the best choices of dose and schedule. Studies identifying the dynamically-linked
      index (dose fractionation studies) and the size of the index to obtain a specific
      amount of bacterial kill can be performed in both systems. Studies to examine
      dosing regimens that will help suppress resistance emergence are best done in the
      HFIM.

PMID- 29035730
TI  - Features of mood associated with high body weight in females with fibromyalgia.
AB  - BACKGROUND: Fibromyalgia (FM) is a common syndrome whose main characteristic is
      chronic widespread musculoskeletal pain, the severity of which is frequently
      worsened by concomitant obesity. Major depression (MD), particularly as part of a
      bipolar spectrum disorder (BSD), is associated with both obesity and FM.
      OBJECTIVE: To evaluate the relationship between lifetime MD, hypomanic symptoms
      and the body mass index (BMI) in patients with FM. METHOD: Of the 115 patients
      originally screened, 87 women with FM finally entered the study. Forty-nine
      patients (57%) had a lifetime diagnosis of MD, assessed by a structured clinical
      interview based on DSM-IV criteria, and four of them (4.6%) had a current MD
      episode. Lifetime hypomanic symptoms were measured by means of the self-rated
      Hypomania Checklist. According to the international criteria for BMI, FM patients
      were classified as under/normal-weight (61%), overweight (30%) and obese (9%).
      RESULTS: 62 patients (71.2%) with FM had a bipolar spectrum disorder (BSD).
      Thirty (48.3%) of them met criteria for bipolar II disorder, 32 (51,6%) for
      bipolar disorder NOS (18 FM patients with MD associated to sub-syndromal
      hypomanic syndrome and 14 with hypomanic syndrome without MD). No patient had a
      bipolar I disorder. Only one patient met the criteria for a major depressive
      disorder (MDD). There was no significant difference in mean BMI between the
      patients with and without a lifetime diagnosis of MD, but there was a positive
      association between the level of hypomanic symptoms and BMI values (p<0.009).
      When hypomania was considered categorically as hypomanic syndrome there was no
      significant effect on BMI. CONCLUSIONS: Our finding adds to previous evidence
      indicating that hypomanic symptoms are a central feature of FM. In the case of
      the early identification of high-level hypomanic symptoms, body weight should be
      closely monitored in order to prevent obesity and its detrimental impact on
      females with FM.

PMID- 29035732
TI  - Development and validation of an automated delirium risk assessment system (Auto
      DelRAS) implemented in the electronic health record system.
AB  - BACKGROUND: A key component of the delirium management is prevention and early
      detection. OBJECTIVE: To develop an automated delirium risk assessment system
      (Auto-DelRAS) that automatically alerts health care providers of an intensive
      care unit (ICU) patient's delirium risk based only on data collected in an
      electronic health record (EHR) system, and to evaluate the clinical validity of
      this system. DESIGN: Cohort and system development designs were used. SETTING:
      Medical and surgical ICUs in two university hospitals in Seoul, Korea.
      PARTICIPANTS: A total of 3284 patients for the development of Auto-DelRAS, 325
      for external validation, 694 for validation after clinical applications. METHODS:
      The 4211 data items were extracted from the EHR system and delirium was measured
      using CAM-ICU (Confusion Assessment Method for Intensive Care Unit). The
      potential predictors were selected and a logistic regression model was
      established to create a delirium risk scoring algorithm to construct the Auto
      DelRAS. The Auto-DelRAS was evaluated at three months and one year after its
      application to clinical practice to establish the predictive validity of the
      system. RESULTS: Eleven predictors were finally included in the logistic
      regression model. The results of the Auto-DelRAS risk assessment were shown as
      high/moderate/low risk on a Kardex screen. The predictive validity, analyzed
      after the clinical application of Auto-DelRAS after one year, showed a
      sensitivity of 0.88, specificity of 0.72, positive predictive value of 0.53,
      negative predictive value of 0.94, and a Youden index of 0.59. CONCLUSIONS: A
      relatively high level of predictive validity was maintained with the Auto-DelRAS
      system, even one year after it was applied to clinical practice.

PMID- 29035731
TI  - Postoperative Adjuvant Sorafenib or Sunitinib for Nonmetastatic Renal Cell
      Carcinoma with Venous Tumor Thrombus: a Prospective Cohort Study.
AB  - PURPOSE: To evaluate the efficacy and safety of antiangiogenic agents (sorafenib
      and sunitinib) as postoperative adjuvant therapy in patients with nonmetastatic
      renal cell carcinoma (RCC) and venous tumor thrombus (VTT). MATERIAL AND METHODS:
      From March 2006 to January 2016, 147 patients who met the inclusion criteria were
      enrolled; 27 patients received sorafenib, and 17 patients received sunitinib.
      After radical nephrectomy and thrombectomy, the duration of maintenance targeted
      medication treatment was approximately 1 year. The primary objective was to
      compare disease-free survival (DFS) between each experimental group and control.
      Secondary end points included overall survival (OS) and toxic effects. RESULTS:
      The three groups were well balanced in terms of age, body mass index, gender,
      performance status, medical history, American Society of Anesthesiologists score,
      surgical approach, and tumor side and size. However, more patients receiving
      adjuvant therapy had inferior vena cava tumor thrombus. DFS and OS did not differ
      significantly between groups (P=.459 and .871, respectively). After adjusting for
      potential confounding factors, results of multivariate analysis proved that
      postoperative adjuvant therapy was not an independent factor for predicting DFS
      and OS (P>.05 for both). The subgroup analyses for inferior vena cava tumor
      thrombus found similar results. The common adverse events were hand-foot
      syndrome, diarrhea, fatigue, and neutropenia. The adverse effects were mild in
      both groups, and the incidence was not significantly different between sorafenib
      and sunitinib. CONCLUSIONS: Adjuvant treatment postoperatively with sorafenib or
      sunitinib showed no survival benefit relative to control for patients with
      nonmetastatic RCC and VTT in a prospective cohort study.

PMID- 29035733
TI  - How does parental cancer affect adolescent and young adult offspring? A
      systematic review.
AB  - OBJECTIVES: To i) identify and synthesise evidence published since 2007 regarding
      the impact of parental cancer on adolescent and young adult offspring, ii)
      identify methodological and evidence gaps addressed during this period and iii)
      highlight those requiring further attention. DESIGN: A systematic review and
      thematic synthesis of peer reviewed literature regarding the impact of parental
      cancer upon AYA offspring. DATA SOURCES: Online searches of CINAHL, Embase,
      Medline, PsychInfo and Scopus databases were conducted. Reference lists of
      included articles were screened and additional searches by prominent authors were
      performed. REVIEW METHODS: Study selection, data extraction and quality analysis
      was undertaken by three independent researchers. Extracted study data was
      iteratively reviewed and discussed to achieve consensus regarding thematic
      synthesis of included studies. RESULTS: Database and hand-searching yielded 1730
      articles, 54 of which were included in the final synthesis. Included studies are
      discussed with respect to the following themes: i) study design and quality; ii)
      measurement and sampling; iii) positive and negative aspects of parental cancer;
      iv) needs; v) communication and information; vi) coping strategies; vii)
      interventions; and viii) family functioning and other predictors. Twenty-nine
      studies reported negative impacts related to parental cancer, while eight
      identified positive outcomes related to post-traumatic growth. Five returned null
      or mixed findings. Unmet needs were frequently explored and a new validated
      measure developed. Communication and information were particularly important for
      offspring, though these needs were often unmet and parents wanted guidance
      regarding discussions with their children. Offspring may adopt a variety of
      coping strategies, some of which appear maladaptive, and may cycle between
      different approaches. Few evaluations of interventions were identified, and
      further work in this area is needed. Further evidence has emerged that poorer
      family functioning and other family and illness-related factors predict worse
      psychosocial outcomes for offspring, however evidence for other predictors such
      as age and gender remain mixed. CONCLUSIONS: Additional evidence for the negative
      psychosocial impact of parental cancer on adolescent and young adult offspring,
      their needs, and factors predicting psychosocial outcomes has emerged in the last
      decade. However, substantial gaps and methodological issues remain and evidence
      for the development, efficacy or implementation of interventions for this
      population is very limited. There is also a clear need for greater focus on
      bereaved and young adult offspring and those from non-western cultural groups,
      who remain under-represented in research conducted to date.

PMID- 29035734
TI  - Comparison of constitutive and thiabendazole-induced expression of five
      cytochrome P450 genes in fourth-stage larvae of Haemonchus contortus isolates
      with different drug susceptibility identifies one gene with high constitutive
      expression in a multi-resistant isolate.
AB  - Benzimidazoles (BZs) remain amongst the most widely used anthelmintic drug
      classes against gastro-intestinal nematode infections, although their efficacy is
      increasingly compromised by resistance. The primary underlying mechanisms for BZ
      resistance are single-nucleotide polymorphisms (SNPs) in the isotype 1 beta
      tubulin gene causing the substitutions F167Y, E198A or F200Y. However, resistance
      is believed to be multi-genic and previous studies have shown that isolates
      carrying 90-100% F200Y can vary considerably in their resistance level in the egg
      hatch assay (EHA). Cytochrome P450 monooxygenases (CYPs) are associated with drug
      resistance in mammals and arthropods and have been considered as mediators of
      anthelmintic resistance. In Caenorhabditis elegans, several members of the
      CYP34/35 and CYP31 families are BZ and/or xenobiotic inducible and thiabendazole
      (TBZ) is metabolised by CYP35D1. Here, expression of all 5 CYPs closely related
      to the C. elegans CYP34/35 and CYP31 families was investigated in fourth-stage
      larvae of two susceptible and three BZ-resistant Haemonchus contortus isolates
      following in vitro exposure to TBZ for 3 and 6 h using real-time RT-PCR. The
      resistance status of all isolates was determined using EHAs and quantification of
      resistance-associated beta-tubulin SNPs using pyrosequencing. While none of the
      CYPs was TBZ inducible, constitutive expression of CYP34/35 family member
      HCOI100383400 was significantly 2.4-3.7-fold higher in the multi-drug resistant
      WR isolate with the strongest BZ resistance phenotype compared to susceptible and
      intermediate-level BZ-resistant isolates. Although this increase is only
      moderate, HCOI100383400 might still be involved in high-level BZ resistance by
      further decreasing susceptibility in isolates already carrying 100% of a beta
      tubulin SNP causing BZ resistance. Lower transcript levels were observed for all
      CYPs in the intermediately resistant IRE isolate in comparison to the susceptible
      HcH isolate, which, except for CYP HCOI01579500, were statistically non
      significant. This suggests that none of the investigated CYPs may contribute to
      protection against TBZ in this particular isolate.

PMID- 29035736
TI  - Mechanotransduction of human pluripotent stem cells cultivated on tunable cell
      derived extracellular matrix.
AB  - Cell-derived matrices (CDM) are becoming an attractive alternative to
      conventional biological scaffolding platforms due to its unique ability to
      closely recapitulate a native extracellular matrix (ECM) de novo. Although cell
      substrate interactions are recognized to be principal in regulating stem cell
      behavior, very few studies have documented the acclimation of human pluripotent
      stem cells (hPSCs) on pristine and altered cell-derived matrices. Here, we
      investigate crosslink-induced mechanotransduction of hPSCs cultivated on
      decellularized fibroblast-derived matrices (FDM) to explore cell adhesion,
      growth, migration, and pluripotency in various biological landscapes. The results
      showed either substrate-mediated induction or inhibition of the Epithelial
      Mesenchymal-Transition (EMT) program, strongly suggesting that FDM stiffness can
      be a dominant factor in mediating hPSC plasticity. We further propose an optimal
      FDM substratum intended for long-term hPSC cultivation in a feeder-free niche
      like microenvironment. This study carries significant implications for hPSC
      cultivation and encourages more in-depth studies towards the fundamentals of hPSC
      CDM interactions.

PMID- 29035735
TI  - Transcriptome profiling identifies genes/pathways associated with experimental
      resistance to paromomycin in Leishmania donovani.
AB  - Widespread resistance towards antimony and reports of relapses following
      miltefosine treatment has severely affected the management of visceral
      leishmaniasis (VL) in the Indian subcontinent. Paromomycin (PMM), an
      aminoglycoside antibiotic, has been licensed for VL treatment in India in 2007.
      Although its use is still restricted in the field, unraveling the molecular
      mechanism of resistance towards PMM is the key to preserve the drug. In this
      study, PMM resistant lines were selected up to 100 MUM of PMM in three distinct
      field isolates of Leishmania donovani at promastigote stage. The resistance
      induced at promastigote level was also evident in amastigotes which showed 6 fold
      decreases in PMM susceptibility. Comparative transcriptome profiling of PMM
      resistant (PMM-R) and the corresponding PMM sensitive (PMM-S) parasites revealed
      modulated expression of 500 genes (1.5 fold cut off) in PMM-R parasites. Selected
      genes were validated for their modulated expression by quantitative real-time
      PCR. Functional classification and pathway analysis of modulated genes indicated
      probable adaptations in drug resistant lines which included a) reduced oxidative
      phosphorylation; b) increased glycosomal succinate fermentation and substrate
      level phosphorylation; c) dependency on lipids and amino acids for energy
      generation; d) reduced DNA synthesis and increased DNA damage repair and e)
      decreased protein synthesis and degradation. Interestingly, PMM-R parasites
      showed a marked increase in PMM susceptibility in presence of verapamil and
      amlodipine, antagonists of Ca2+ channel that are also modulators of ABC
      transporters. Moreover, infection of macrophages by PMM-R parasites led to
      modulated nitric oxide (NO) levels while reactive oxygen species (ROS) level
      remained unaltered. The present study highlights the putative mechanisms of PMM
      resistance in Leishmania.

PMID- 29035737
TI  - Rethinking liquid biopsy: Microfluidic assays for mobile tumor cells in human
      body fluids.
AB  - Traditionally, liquid biopsy is a blood test involving the harvesting of tumor
      materials from peripheral blood. Tumor cells from non-blood body fluids have
      always been clinically available in cytological examinations but limited for use
      in differential diagnosis due to the low sensitivity of conventional
      cytopathology. With the recent significant progress in microfluidic and
      downstream molecular technologies, liquid biopsies have now evolved to include
      harvesting tumor cells and DNA fragments in all kinds of non-blood body fluids.
      This expansion into general body fluids presages the notion that liquid biopsy
      could soon be used in competition, as well as, in complementarity with tissue
      biopsy. Preliminary research of fluid-harvested tumor materials to spot early
      stage tumors, monitor disease progression for metastasis and recurrence, and
      detect chemoresistance have been reported. To reflect the propagation of tumor
      cells in non-blood body fluids, we introduced the term Mobile Tumor Cells (MTCs),
      in lieu of the widely accepted term of circulating tumor cells (CTCs) resident in
      the bloodstream. Our review starts with a discussion on the clinical significance
      of MTCs, followed by a presentation of microfluidic techniques for MTC capture
      and various strategies for their identification. Hopefully, the phenotypic and
      genomic data acquired from harvested MTCs can be used to guide and improve cancer
      treatment decisions.

PMID- 29035738
TI  - Thrombin-activatable fluorescent peptide incorporated gold nanoparticles for dual
      optical/computed tomography thrombus imaging.
AB  - Thrombosis is an important pathophysiologic phenomenon in various cardiovascular
      diseases, which can lead to oxygen deprivation and infarction of tissues by
      generation of a thrombus. Thus, direct thrombus imaging can provide beneficial in
      diagnosis and therapy of thrombosis. Herein, we developed thrombin-activatable
      fluorescent peptide (TAP) incorporated silica-coated gold nanoparticles (TAP
      SiO2@AuNPs) for direct imaging of thrombus by dual near-infrared fluorescence
      (NIRF) and micro-computed tomography (micro-CT) imaging, wherein TAP molecules
      were used as targeted thrombin-activatable peptide probes for thrombin-specific
      NIRF imaging. The freshly prepared TAP-SiO2@AuNPs had an average diameter of 39.8
      +/- 2.55 nm and they showed the quenched NIRF signal in aqueous condition, due to
      the excellent quenching effect of TAP molecules on the silica-gold nanoparticle
      surface. However, 30.31-fold higher NIRF intensity was rapidly recovered in the
      presence of thrombin in vitro, due to the thrombin-specific cleavage of quenched
      TAP molecules on the gold particle surface. Furthermore, TAP-SiO2@AuNPs were
      successfully accumulated in thrombus by their particle size-dependent capturing
      property, and they presented a potential X-ray absorption property in a dose
      dependent manner. Finally, thrombotic lesion was clearly distinguished from
      peripheral tissues by dual NIRF/micro-CT imaging after intravenous injection of
      TAP-SiO2@AuNPs in the in situ thrombotic mouse model, simultaneously. This study
      showed that thrombin-activatable fluorescent peptide incorporated silica-coated
      gold nanoparticles can be potentially used as a dual imaging probe for direct
      thrombus imaging and therapy in clinical applications.

PMID- 29035739
TI  - Physical oncology: New targets for nanomedicine.
AB  - Physical oncology is an emerging paradigm which recognizes tissue mechanics, per
      se, as an active modulator of tumorigenesis, treatment resistance and clinical
      outcome, mediated by mechanosignaling pathways, matrix remodeling and physical
      barriers to drugs. The tumor microenvironment displays abnormal physical
      properties in comparison to healthy tissue which contribute to cancer progression
      and resistance to current treatments. Physical aberrancies comprise the chaotic
      organization of tumor vasculature, an increased interstitial pressure, an
      increased solid stress, hypoxia, an abundant extracellular matrix and a
      progressive stiffening of solid tumors. The physical barriers in tumors are of
      critical importance, as tissue mechanics compromises drug delivery, reduces
      immune cell infiltration and promotes disease aggressiveness. All these physical
      hallmarks of cancer, although not fully understood, are inspiring new anticancer
      strategies aiming to target and normalize the physical anomalies of solid tumors,
      particularly in the field of nanomedicine. Here we summarize the recent paradigm
      shift of physical oncology and review some of the proposed strategies using
      nanomaterials to tackle the tumor microenvironment and its aberrant physical
      properties. Nanomedicine might harness the features of the tumor microenvironment
      in order to improve nanoparticle and drug delivery, or propose nano-agents that
      can be activated on demand to achieve a tailored spatio-temporal modulation of
      the tumor microenvironment, reduce tumor pressure and stiffness and alleviate the
      resistance to current treatments.

PMID- 29035740
TI  - Memory Age Identity as a predictor of cognitive function in the elderly: A 2-year
      follow-up study.
AB  - BACKGROUND: There is a growing interest in finding psychosocial predictors
      related to cognitive function. In our previous research, we conducted a cross
      sectional study on memory age identity (MAI) and found that MAI might be
      associated with objective cognitive performance in non-cognitively impaired
      elderly. A longitudinal study was conducted to better understand the importance
      of MAI as a psychosocial predictor related to objective cognitive function.
      METHODS: Data obtained from 1345 Korean subjects aged 60 years and above were
      analyzed. During the two-year follow-up, subjective memory age was assessed on
      three occasions using the following question: How old do you feel based on your
      memory? Discrepancy between subjective memory age and chronological age was then
      calculated. We defined this value as 'memory age identity (MAI)'. A generalized
      estimating equation (GEE) was then obtained to demonstrate the relationship
      between MAI and Korean version-Mini Mental State Examination (K-MMSE) score over
      the 2 years of study. RESULTS: MAI was found to significantly (beta=-0.03, p<
      0.0001) predict objective cognitive performance in the non-cognitively impaired
      elderly. CONCLUSION: MAI may be a potential psychosocial predictor related to
      objective cognitive performance in the non-cognitively impaired elderly.

PMID- 29035741
TI  - Association between psychological distress, subjective cognitive complaints and
      objective neuropsychological functioning in brain tumor patients.
AB  - OBJECTIVES: Psychological distress and cognitive impairment are common
      complications in patients with brain tumors that are associated with poor quality
      of life and worse prognosis. This pilot study aimed to evaluate the associations
      between psychological distress, subjective cognitive complaints and baseline
      neuropsychological performance of brain tumor patients before neurosurgery.
      PATIENTS AND METHODS: Sixty-two patients with various brain tumors referred for
      routine neuropsychological assessment 2-3days before neurosurgery participated in
      the study. Short neuropsychological assessment battery was used to evaluate
      attention and executive functions, memory and verbal fluency. Presence of
      cognitive complaints was evaluated during neuropsychological interview using
      standardized symptoms checklist. Level of psychological distress was assessed
      using the Hospital Anxiety and Depression Scale. RESULTS: Various attention and
      executive function problems were reported by 13-58% patients; memory problems by
      8-63%; language problems by 10-58% of patients. 36-57% of patients scored below
      5th percentile on objective memory measures; 32-45% on attention measures and 11
      27% on verbal fluency. However, correlation between objective neuropsychological
      findings and subjective cognitive complaints was weak, ranging from 0.0 to 0.3.
      45% of patients met criteria for increased psychological distress. Psychological
      distress was associated with subjective cognitive complaints but failed to
      predict objective neuropsychological findings. Brain tumor histological
      diagnosis, side and location were not related to neuropsychological functioning.
      CONCLUSION: Cognitive impairment and psychological distress are highly prevalent
      in BT patients before neurosurgery. Although depression and distress may
      adversely impact quality of life and prognosis of BT patients, our current
      findings do not confirm that distress has strong negative impact on objective
      preoperative cognitive functioning. However, it is related to worse subjective
      evaluation of one's cognitive abilities. Therefore, objective neuropsychological
      assessment of cognitive functions is highly recommended despite concern.

PMID- 29035742
TI  - How does solvation in the cell affect protein folding and binding?
AB  - The cellular environment is highly diverse and capable of rapid changes in solute
      composition and concentrations. Decades of protein studies have highlighted their
      sensitivity to solute environment, yet these studies were rarely performed in
      situ. Recently, new techniques capable of monitoring proteins in their natural
      context within a live cell have emerged. A recurring theme of these
      investigations is the importance of the often-neglected cellular solvation
      environment to protein function. An emerging consensus is that protein processes
      in the cell are affected by a combination of steric and non-steric interactions
      with this solution. Here we explain how protein surface area and volume changes
      control these two interaction types, and give recent examples that highlight how
      even mild environmental changes can alter cellular processes.

PMID- 29035743
TI  - Transmission of henipaviruses.
AB  - The genus Henipavirus has expanded rapidly in geographic range, number of
      species, and host range. Hendra and Nipah virus are two henipaviruses known to
      cause severe disease in humans with a high case-fatality rate. Pteropid spp. bats
      are the natural reservoir of Hendra and Nipah virus. From these bats, virus can
      be transmitted to an amplifying host, horses and pigs, and from these hosts to
      humans, or the virus can be transmitted directly to humans. Although the main
      route of shedding varies between host species, close contact is required for
      transmission in all hosts. Understanding the transmission routes of Hendra and
      Nipah virus in their respective hosts is essential for devising strategies to
      block zoonotic transmission.

PMID- 29035744
TI  - A systematic review of instrumental variable analyses using geographic region as
      an instrument.
AB  - BACKGROUND: Instrumental variables analysis is a methodology to mitigate the
      effects of measured and unmeasured confounding in observational studies of
      treatment effects. Geographic area is increasingly used as an instrument.
      METHODS: We conducted a literature review to determine the properties of
      geographic area in studies of cancer treatments. We identified cancer studies
      performed in the United States which incorporated instrumental variable analysis
      with area-wide treatment rate within a geographic region as the instrument. We
      assessed the degree of treatment variability between geographic regions, assessed
      balance of measured confounders afforded by geographic area and compared the
      results of instrumental variable analysis to those of multivariable methods.
      RESULTS: Geographic region as an instrument was relatively common, with 22
      eligible studies identified, many of which were published in high-impact
      journals. Treatment rates did not vary greatly by geographic region. Covariates
      were not balanced by the instrument in the majority of studies. Eight out of
      eleven studies found statistically significant effects of treatment on
      multivariable analysis but not for instrumental variables, with the central
      estimates of the instrumental variables analysis generally being closer to the
      null. CONCLUSIONS: We recommend caution and an investigation of IV assumptions
      when considering the use of geographic region as an instrument in observational
      studies of cancer treatments. The value of geographic region as an instrument
      should be critically evaluated in other areas of medicine.

PMID- 29035745
TI  - Bio-functionalization of grade V titanium alloy with type I human collagen for
      enhancing and promoting human periodontal fibroblast cell adhesion - an in-vitro
      study.
AB  - Surface modification of medical grade V titanium alloy (Ti-6Al-4V) with
      biomolecules is an important and vital step for tailoring it for various
      biomedical applications. Present study investigates theinfluence of type I human
      collagen (T1HC) bio-conjugation through a three stage process. Polished grade V
      titanium alloy discs were functionalizedwith free OH group by means of controlled
      heat and alkali treatment followed by coating of 3-aminopropyltriethoxy (APTES)
      silane couplingagent. T1HC were bio-conjugated through 1-ethyl-3-(3-dimethyl
      aminopropyl) carbodiimide hydrochloride N-hydroxysuccinimide (EDCNHS)coupling
      reaction. At each stage, grade V titanium alloy surfaces were characterized by
      atomic force microscopy (AFM), scanning electronmicroscopy (SEM), Fourier
      transform infrared spectroscopy (FTIR) and Xrayphotoelectron spectroscopy (XPS).
      FTIR and XPS studies confirms thecovalent attachment of APTES with titanium alloy
      surface while terminalamine groups of APTES remained free for further attachment
      of T1HCthrough covalent bond. Aqueous stability of bio-conjugated titanium
      discsat various pH and time intervals (i.e. at pH of 5.5, 6.8 and 8.0 at
      timeinterval of 27 and 48h) confirmed the stability of T1HC bioconjugated
      collagen on titanium surface. Further human periodontalfibroblast cell line
      (HPdlF) culture revealed enhanced adhesion on theT1HC bio-conjugated surface
      compared to the polystyrene and polishedgrade V titanium alloy surfaces.

PMID- 29035746
TI  - The exploration of endocytic mechanisms of PLA-PEG nanoparticles prepared by
      coaxialtri-capillary electrospray-template removal method.
AB  - The nano-sized poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) particles with
      core-shell structure were efficiently prepared by using coaxial tri-capillary
      electrospray-template removal method. The cellular uptake mechanism,
      intracellular distribution and exocytosis in A549 cell model of electrosprayed
      PLA-PEG nanoparticles were systemically studied. The drug release behavior of
      electrosprayed PLA-PEG nanoparticles were also investigated. Our results showed
      that PLA-PEG nanoparticles can be endocytosed quickly by A549 cells. The cellular
      uptake of PLA-PEG nanoparticles was an energy dependent endocytosis process.
      Caveolae-mediated endocytosis was only one of endocytosis pathways in A549 cells
      for PLA-PEG nanoparticles, while clathrin mediated endocytosis was not involved
      in the endocytosis process. The endocytosed PLA-PEG nanoparticles enriched in the
      head of A549 cells and only a small amount of them was transported into lysosome
      after 24h incubation. These findings provided insights into the application of
      electrosprayed PLA-PEG nanoparticles in nano drug delivery field.

PMID- 29035748
TI  - Body dissatisfaction predicts poor behavioral weight loss treatment adherence in
      overweight Mexican American women.
AB  - Poor adherence poses a major barrier to the success of behavioral weight loss
      (BWL) programs, particularly for overweight Mexican American women. Given the
      high prevalence and costs of overweight/obesity, factors that contribute to
      attendance and adherence problems should be identified, especially in ethnic
      minority populations. The current study examined the role of pre-treatment body
      dissatisfaction and depression in predicting attendance and adherence in a BWL
      intervention. Ninety-nine overweight/obese Mexican American women enrolled in the
      intervention and completed baseline measures. Eighty-one of the women attended at
      least one treatment session and provided measures of dietary and physical
      activity adherence. Simultaneous linear regression analyses suggested that
      although higher levels of body dissatisfaction and depression each played unique
      roles in predicting poorer attendance, only body dissatisfaction predicted
      adherence. Specifically, higher body dissatisfaction predicted poorer treatment
      adherence. Findings highlight the importance of addressing body dissatisfaction
      early in BWL treatment to increase attendance and adherence.

PMID- 29035747
TI  - Studies on the adsorption and desorption of mitoxantrone to lauric acid/albumin
      coated iron oxide nanoparticles.
AB  - A rational use of superparamagnetic iron oxide nanoparticles (SPIONs) in drug
      delivery, diagnostics, and other biomedical applications requires deep
      understanding of the molecular drug adsorption/desorption mechanisms for proper
      design of new pharmaceutical formulations. The adsorption and desorption of the
      cytostatic Mitoxantrone (MTO) to lauric acid-albumin hybrid coated particles
      SPIONs (SEONLA-HSA) was studied by Fourier transform infrared spectroscopy
      (FTIR), dynamic light scattering (DLS), surface titration, release experiments
      and small-angle neutron and X-ray scattering. Such MTO-loaded nanoparticles have
      shown very promising results in in vivo animal models before, while the exact
      binding mechanism of the drug was unknown. SEONLA-HSA formulations have shown
      better stability under drug loading in comparison with uncoated nanoparticle and
      sustainable drug release to compare with protein solution. Adsorption of MTO to
      SEONLA-HSA leads to decreasing of absolute value of zeta potential and repulsive
      interaction among particles, which points to the location of separate molecules
      of MTO on the outer surface of LA-HSA shell.

PMID- 29035749
TI  - Chemical remodeling cell surface glycans for immunotargeting of tumor cells.
AB  - Recruitment of human endogenous antibodies to target and eliminate tumor cells is
      a promising therapeutic strategy in the biomedical field. Current antibody
      recruiting molecules are typically bi-functional agents that utilize cell-surface
      receptor binding property for targeting. This approach has intrinsic limitations
      due to the heterogeneity of tumor cells and the limited number of receptors on
      the cell surface. Here we report a targeting strategy based on remodeling of cell
      surface glycans through metabolic engineering and bioorthogonal chemical
      ligation. In vitro cultured tumor cells and in vivo xenograft tumors were
      actively remodeled with rhamnose carbohydrate epitopes, which were capable of
      recruiting endogenous anti-rhamnose antibodies and activating complement-mediated
      cell cytotoxicity. This study highlights the therapeutic potential for modulating
      endogenous immune response through cell-surface glycan engineering.

PMID- 29035750
TI  - Attention and the sense of agency: A review and some thoughts on the matter.
AB  - Much is now known about the sense of agency and how it is produced. What is
      lacking, though, is an understanding of how it relates to other cognitive domains
      and operations. Here, the relationship between the sense of agency and attention
      is explored. A review of the literature suggests that attention is involved in
      the sense of agency in (at least) two key ways. First, agency processing is
      dependent on attentional resources. Second, attentional enhancement is necessary
      for extraneous information to have an influence over the sense of agency. These
      are discussed and some suggestions for future research are offered.

PMID- 29035752
TI  - Regulation of oxidative stress and mineral nutrient status by selenium in arsenic
      treated crop plant Oryza sativa.
AB  - The present study was conducted to examine the impact of selenium (Se) on mineral
      nutrient status and oxidative stress in crop plant Oryza sativa treated with
      arsenic (As). Scanning electron microscopy (SEM) coupled with Energy dispersive x
      ray spectroscopy (EDS) study revealed the morphological deformities in leaf veins
      along with granular deposition on the leaf surface. The EDS analysis exhibited
      loss of elements (S, Si, Cl, K, Ca, Fe and Cu) in As(III) treatment in rice roots
      as compared to untreated root. In the case of As(III) treated shoot, changes in
      elements content in term of percent atomic weight was K (1.17-0.90%), Cl (1.04
      24.75%), Na (0.65-3.52%) and S (0.49-2.52%) when compared with untreated shoot.
      The result of EDS analysis showed that As limits the concentration of important
      mineral elements present in the rice root and shoot. Rice plant treated with Se
      (10uM) and sub lethal dose of As(III) (60uM) showed better growth responses in
      term of root, shoot length (11.4% and 10.71%, respectively), biomass (11.7%),
      reduced malonyldialdehyde content (35.14%) and stimulated antioxidant level
      indicating better As tolerance potential against As. Further, a selenium
      dependent significant reduction in As accumulation was also observed in root
      (14.24%) and shoot (23.78%) of rice plant when compared with plant treated with
      As alone. This study highlights the potential of Se to ameliorate the
      ecotoxicological risks associated with the As buildup in agricultural land.

PMID- 29035753
TI  - Toxic inorganic pollutants in foods from agricultural producing areas of Southern
      Italy: Level and risk assessment.
AB  - This study focused on the inorganic environmental contaminants in specific food
      products which form part of the food chain of the population residing in the area
      of Southern Italy (Gela) where there is a high mortality rate linked to tumor
      diseases and congenital malformations. Determination of toxic metals was
      performed by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). The
      toxicological data for every toxic element has been applied to evaluate the risk
      for the consumer by calculating the amount of potentially toxic element that
      would ingest an average of 60kg weight individual adult. The analysis of the
      investigated samples shows a high level of metal contamination which can be
      linked both to the polluted water and air. The obtained results give us an idea
      about the agricultural products contamination and possible exposure of local
      people through the food chain.

PMID- 29035751
TI  - Intercellular transfer of pathogenic alpha-synuclein by extracellular vesicles is
      induced by the lipid peroxidation product 4-hydroxynonenal.
AB  - Parkinson's disease (PD) is characterized by accumulations of toxic alpha
      synuclein aggregates in vulnerable neuronal populations in the brainstem,
      midbrain, and cerebral cortex. Recent findings suggest that alpha-synuclein
      pathology can be propagated transneuronally, but the underlying molecular
      mechanisms are unknown. Advances in the genetics of rare early-onset familial PD
      indicate that increased production and/or reduced autophagic clearance of alpha
      synuclein can cause PD. The cause of the most common late-onset PD is unclear,
      but may involve metabolic compromise and oxidative stress upstream of alpha
      synuclein accumulation. As evidence, the lipid peroxidation product 4
      hydroxynonenal (HNE) is elevated in the brain during normal aging and moreso in
      brain regions afflicted with alpha-synuclein pathology. Here, we report that HNE
      increases aggregation of endogenous alpha-synuclein in primary neurons and
      triggers the secretion of extracellular vesicles (EVs) containing cytotoxic
      oligomeric alpha-synuclein species. EVs released from HNE-treated neurons are
      internalized by healthy neurons which as a consequence degenerate. Levels of
      endogenously generated HNE are elevated in cultured cells overexpressing human
      alpha-synuclein, and EVs released from those cells are toxic to neurons. The EV
      associated alpha-synuclein is located both inside the vesicles and on their
      surface, where it plays a role in EV internalization by neurons. On
      internalization, EVs harboring pathogenic alpha-synuclein are transported both
      anterogradely and retrogradely within axons. Focal injection of EVs containing
      alpha-synuclein into the striatum of wild-type mice results in spread of
      synuclein pathology to anatomically connected brain regions. Our findings suggest
      a scenario for late-onset PD in which lipid peroxidation promotes intracellular
      accumulation and then extrusion of EVs containing toxic alpha-synuclein species;
      the EVs are then internalized by adjacent neurons, so propagating the
      neurodegenerative process.

PMID- 29035754
TI  - Regulation of autophagy factors by oxidative stress and cardiac enzymes imbalance
      during arsenic or/and copper induced cardiotoxicity in Gallus gallus.
AB  - Basal autophagy has an indispensable role in the functioning and maintenance of
      cardiac geometry under physiological conditions. Recently, increasing evidence
      has demonstrated that arsenic (As)/copper (Cu) play important roles in the
      autophagy of the heart. The current study was to evaluate whether oxidative
      damage by As or/and Cu was correlated with autophagy through the
      phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of
      rapamycin (mTOR) pathway in the heart of birds. Arsenic trioxide (30mg/kg) or/and
      cupric sulfate (300mg/kg) were administered in a basal diet to male Hy-line
      chickens (one-day-old) for 12 weeks. The results showed that heart weight/body
      weight ratio decreased in the As + Cu group only at 4, 8 and 12 weeks. Moreover,
      we observed that As or/and Cu decreased high-density lipoprotein cholesterol (HDL
      C) concentrations, increased total cholesterol (T-CHO) concentrations and cardiac
      enzymes activities in the serum. On the other hand, As or/and Cu significantly
      reduced the activities of total antioxidant (T-AOC), superoxide dismutase (SOD),
      catalase (CAT), glutathione peroxidase (GSH-Px)) along with decreased nonenzymic
      antioxidant (glutathione (GSH)) concentrations and increased malondialdehyde
      (MDA) concentrations in the heart. Furthermore, As or/and Cu could induce
      autophagy in the heart of chickens through decreased mRNA levels of TORC1, TORC2,
      microtubule associated light chains 3-I (LC3-I) and increased PI3K, AKT1,
      Beclin1, autophagy associated gene 4B (Atg4B), microtubule associated light
      chains 3-II (LC3-II), autophagy associated gene 5 (Atg5) and Dynein. Meanwhile,
      ultrastructural examinations showed that As/Cu could result in the appearance of
      autolygosomes, autophagic vacuoles and double-membrane structures in the heart.
      In conclusion, As or/and Cu induced cardiac damage and autophagy via elevating
      cardiac enzymes activities, inducing oxidative stress and activating the
      PI3K/AKT/mTORC pathway in heart of chickens. Moreover, As and Cu had a possible
      synergistic relationship in the heart of chickens.

PMID- 29035755
TI  - Antibiotic effects on seed germination and root development of tomato (Solanum
      lycopersicum L.).
AB  - Antibiotics are emerging pollutants released into the environment through
      wastewater and manure or effluents from livestock plants. Compared to the wide
      literature on the effects of antibiotics on the development of drug-resistant
      bacteria and on the adverse effects on animals and human beings, the effects on
      plants are less investigated. Here we evaluated the effects of four antibiotics
      (cloramphenicol: CAP, spiramycin: SPR, spectinomycin: SPT, vancomycin: VAN)
      belonging to different chemical groups, on seed germination and root development
      of tomato (Solanum lycopersicum L. cv. San Marzano). Specifically, seed
      germination and root elongation kinetics, as well as the number of mithotic
      figures in root apical meristem, were studied in relation to different
      concentrations of each antibiotic (0, 0.1, 1, 10, 100, 1000mgL-1) for 10 and 7
      days, respectively. Results showed that seed germination was not affected, but
      root development (root elongation kinetics and cell division) was impaired at
      concentrations from 10mgL-1 (SPT) and 100mgL-1 (CAP) to 1000mgL-1 (SPR and VAN).

PMID- 29035756
TI  - Lymph node wire localization post-chemotherapy: Towards improving the false
      negative sentinel lymph node biopsy rate in breast cancer patients.
AB  - PURPOSE: To evaluate whether the disease status of the pre-neoadjuvant
      chemotherapy (NAC) core biopsied lymph node (preNACBxLN) in patients with node
      positive breast cancer corresponds to nodal status of all surgically retrieved
      lymph nodes (LNs) post-NAC and whether wire localization of this LN is feasible.
      MATERIALS AND METHODS: HIPPA compliant IRB approved retrospective study including
      breast cancer patients (a.) with preNACBxLN confirmed metastases, (b.) who
      received NAC, and (c.) underwent wire localization of the preNACBxLN. Electronic
      medical records were reviewed. Fisher's exact test was used to compare
      differences in residual disease post-NAC among breast cancer subtypes. RESULTS:
      28 women with node positive breast cancer underwent ultrasound guided wire
      localization of the preNACBxLN, without complication. There was no evidence of
      residual nodal disease for 16 patients, with mean 4.4 (median 4) LNs resected. 12
      patients had residual nodal metastases, with mean 9.2 (median 7) LNs resected and
      mean 2.3 (median 2) LNs with tumor involvement. 11 patients had metastases
      detected within the localized LN. One patient had micrometastasis in a sentinel
      LN, despite no residual disease in the preNACBxLN. Patients with luminal A/B
      breast cancer more often had residual nodal metastases (86%) at pathology, as
      compared to patients with HER2+ (20%) and Triple Negative breast cancer (50%),
      though not quite achieving statistical significance (p=0.055). CONCLUSION:
      Ultrasound guided wire localization of the preNACBxLN is feasible and may improve
      detection of residual tumor in patients post-NAC.

PMID- 29035757
TI  - Pulmonary hypertension associated with bronchopulmonary dysplasia in preterm
      infants.
AB  - Bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary hypertension (BPD
      PH) are chronic inflammatory cardiopulmonary diseases with devastating short- and
      long-term consequences for infants born prematurely. The immature lungs of
      preterm infants are ill-prepared to achieve sufficient gas exchange, thus usually
      necessitating immediate commencement of respiratory support and oxygen
      supplementation. These therapies are life-saving, but they exacerbate the tissue
      damage that is inevitably inflicted on a preterm lung forced to perform gas
      exchange. Together, air-breathing and necessary therapeutic interventions disrupt
      normal lung development by aggravating pulmonary inflammation and vascular
      remodelling, thus frequently precipitating BPD and PH via an incompletely
      understood pathogenic cascade. BPD and BPD-PH share common risk factors, such as
      low gestational age at birth, fetal growth restriction and perinatal maternal
      inflammation; however, these risk factors are not unique to BPD or BPD-PH.
      Occurring in 17-24% of BPD patients, BPD-PH substantially worsens the morbidity
      and mortality attributable to BPD alone, thus darkening their outlook; for
      example, BPD-PH entails a mortality of up to 50%. The absence of a safe and
      effective therapy for BPD and BPD-PH renders neonatal cardiopulmonary disease an
      area of urgent unmet medical need. Besides the need to develop new therapeutic
      strategies, a major challenge for clinicians is the lack of a reliable method for
      identifying babies at risk of developing BPD and BPD-PH. In addition to
      discussing current knowledge on pathophysiology, diagnosis and treatment of BPD
      PH, we highlight emerging biomarkers that could enable clinicians to predict
      disease-risk and also optimise treatment of BPD-PH in our tiniest patients.

PMID- 29035758
TI  - Adherence to a Dash-style diet in relation to depression and aggression in
      adolescent girls.
AB  - The aim of this study was to assess adherence to the Dietary Approach to Stop
      Hypertension (DASH) dietary pattern in relation to depression and aggression in
      adolescent girls. The study was carried out among 580 girls aged between 12 and
      18 years of age. DASH scores were determined according to the method of Fung et
      al. A Persian version of the Beck Depression Inventory and Buss-Perry
      questionnaire were used for the assessment of depression and aggression. We
      analysed our data using crude and adjusted models. Adjustments were made for age,
      energy intake, mother's job status, passive smoking, start of menstruation,
      parental death, parental divorce, physical activity level and body mass index,
      using three different models. A high adherence to a Dash-style diet (for
      individuals in the upper quartile) was associated with a lower odds of depression
      compared with subjects with lower adherence (those in the lowest quartile) (OR
      0.47; 95% CI 0.26-0.84, P-value = 0.009); these associations remained significant
      after adjustments. However, we did not obtain any significant relationship
      between a DASH-style diet and aggression. We observed a significant inverse
      relationship between greater adherence to a DASH diet and lower odds of
      depression. Further prospective studies are needed to confirm these findings.

PMID- 29035760
TI  - Engineering nanoreactors using bacterial microcompartment architectures.
AB  - Bacterial microcompartments (BMCs) are organelles that encapsulate enzymes
      involved in CO2 fixation or carbon catabolism in a selectively permeable protein
      shell. Here, we highlight recent advances in the bioengineering of these protein
      based nanoreactors in heterologous systems, including transfer and expression of
      BMC gene clusters, the production of template empty shells, and the encapsulation
      of non-native enzymes.

PMID- 29035759
TI  - The Beliefs about Voices Questionnaire - Revised: A factor structure from 450
      participants.
AB  - Hallucinated voices are common across psychiatric and non-clinical groups. The
      predominant cognitive theory about the impact of voices posits that beliefs about
      voice power ('Omnipotence') and voice intent ('Malevolence'/'Benevolence') play a
      key role in determining emotional and behavioral reactions. The revised Beliefs
      about Voices Questionnaire (BAVQ-R) was designed to assess these constructs,
      together with two styles of responding (Engagement and Resistance). The BAVQ-R is
      widely used in clinical and research settings, yet it has not received validation
      of its constructs and factor structure. This study examined the factor structure
      of the BAVQ-R by combining datasets from five study centers, comprising 450
      participants (belief constructs) and 269 participants (response styles), and
      using confirmatory and exploratory factor analysis. Findings failed to support a
      three factor belief model, instead showing a two-factor structure ('Persecutory
      beliefs' combining Omnipotence and Malevolence constructs, and a Benevolent
      construct). Emotional and behavioral items did not separate. Overall, results
      showed that (i) a two-factor model of beliefs (Persecutory and Benevolent
      beliefs) provides a better fit to the data than a three-factor model, and (ii)
      emotional and behavioral modes of responding items should not be separated.
      Theoretical implications of this finding are discussed in relation to the
      research and therapy.

PMID- 29035761
TI  - Lab-on-a-chip systems for photodynamic therapy investigations.
AB  - In recent years photodynamic therapy (PDT) has received widespread attention in
      cancer treatment due to its smaller surgical trauma, better selectivity towards
      tumor cells, reduced side effects and possibility of repeatable treatment. Since
      cancer is the second cause of death worldwide, scientists constantly seek for new
      potential therapeutic agents including nanotechnology-based photosensitizers used
      in PDT. The new-designed nanostructures must be carefully studied and well
      characterized what require analytically useful and powerful tools that enable
      real progress in nanoscience development. This review describes the current
      status of PDT investigations using microfluidic Lab-on-a-Chip systems, including
      recent developments of nanoparticle-based PDT agents, their combinations with
      different drugs, designs and examples of in vitro applications. This review
      mainly lays emphasis on biological evaluation of FDA approved photosensitizing
      agents as well as newly designed nanophotosensitizers. It also highlights the
      analytical performances of various microfluidic Lab-on-a-chip systems for PDT
      efficacy analysis on 3D culture and discusses microsystems designs in detail.

PMID- 29035762
TI  - High genetic variability of norovirus leads to diagnostic test challenges.
AB  - BACKGROUND: It is important to understand the diagnostic accuracy of multiplex
      panels such as the Luminex xTAG(r) Gastrointestinal Pathogen Panel (GPP) as they
      are increasingly employed for routine diagnostics worldwide. Recent evaluations
      in our laboratory identified lower detection rates of norovirus genogroup II (NoV
      GII) using GPP compared to our laboratory-developed RT-qPCR, Gastroenteritis
      Virus Panel (GVP). OBJECTIVES: To characterize the cases of discordant NoV GII
      results between GPP and GVP and determine the sensitivity of the two assays for
      specific NoV GII genotypes. STUDY DESIGN: We genotyped discordant NoV GII strains
      identified in stool samples or rectal swabs collected prospectively from a cohort
      of children with acute gastroenteritis between December 2014 and July 2016. The
      sensitivities of GVP and GPP for NoV GII were compared by analyses of GVP
      threshold cycle (Ct) and ten-fold serial dilutions of positive samples of various
      NoV GII genotypes. RESULTS: All discordant samples (63/607) were NoV GII positive
      by GVP but negative by GPP. Twenty-two were successfully genotyped, fourteen of
      which were NoV GII genotype 2 (GII.2). The median Ct value of concordant
      positives was lower than that of discordant results (19.8 vs. 33.7; P<0.0001).
      GVP was 10 and at least 10,000-fold more sensitive than GPP in detecting NoV
      GII.3 and GII.2, respectively, but has similar sensitivity for NoV GII.4.
      Discordant GII.2 variant differed genetically from concordant GII.2 variants.
      CONCLUSIONS: GPP has lower sensitivity to detect NoV GII.2 than GVP and its use
      may lead to undetected cases clinically, and an underestimation of NoV disease
      burden at the population level.

PMID- 29035763
TI  - Optimized enzyme-linked immunosorbent assay for detecting cytomegalovirus
      infections during clinical trials of recombinant vaccines.
AB  - BACKGROUND: In clinical trials of cytomegalovirus (CMV) glycoprotein B (gB)
      vaccines, CMV infection is detected by first depleting serum of anti-gB
      antibodies and then measuring anti-CMV antibodies with a commercially available
      enzyme-linked immunosorbent assay (ELISA) kit, with confirmation of positive
      findings by immunoblot. OBJECTIVES: Identification of CMV immunoantigens for the
      development of an ELISA that detects specifically CMV infection in clinical
      samples from individuals immunized with gB vaccines. STUDY DESIGN: Sensitivity
      and specificity of ELISAs using antigenic regions of CMV proteins UL83/pp65,
      UL99/pp28, UL44/pp52, UL80a/pp38, UL57, and UL32/pp150 were measured. RESULTS: An
      IgG ELISA using a UL32/pp150 [862-1048] capture peptide was the most specific
      (93.7%) and sensitive (96.4%) for detecting CMV-specific antibodies in sera. The
      ELISA successfully detected CMV-specific antibodies in 22 of 22 sera of subjects
      who had been vaccinated with a gB vaccine but who had later been infected with
      CMV. The ELISA was linear over a wide range of CMV concentrations (57-16,814
      ELISA units/mL) and was reproducible as indicated by a 5% intra-day and 7% inter
      day coefficients of variation. The signal was specifically competed by UL32/pp150
      [862-1048] peptide but not by CMV-gB or herpes simplex virus 2 glycoprotein D.
      Lipid and hemoglobin matrix did not interfere with the assay. CONCLUSION: The
      UL32/pp150 [862-1048] IgG ELISA can be used for the sensitive and specific
      detection of CMV infection in gB-vaccinated individuals.

PMID- 29035764
TI  - Suitability of fluorescent whitening compounds (FWCs) as indicators of human
      faecal contamination from septic tanks in rural catchments.
AB  - Rural river catchments are impacted by diffuse pollution sources from
      agricultural practices and on-site domestic wastewater treatment systems (DWWTS),
      mainly septic tanks. Methods that can distinguish between contamination sources
      will significantly increase water management efficiency as they will allow for
      the development and application of targeted remediation measures. Fluorescent
      whitening compounds (FWC), are used as optical brighteners in laundry detergents
      and enter the environment through the discharge of domestic wastewater effluents.
      Due to their human specific source and potential simple fluorometric measurement
      this represents a very attractive method to be used by state monitoring agencies.
      In this study the suitability of FWCs as chemical indicators for human faecal
      contamination has been investigated in rural Irish catchments. It was found that
      no quantitative measurements are possible for FWCs in natural waters when using
      simple fluorometric methods. Hence a simple presence/absence approach needs to be
      applied. The detectability of FWCs was quantified and found to decrease with
      higher organic matter content of the river water which has its own fluorescence.
      This enabled the establishment of equations to predict detection limits and
      assess the method's suitability for individual catchments based on organic matter
      concentrations. Furthermore a modified photodecay method is suggested that
      increases sensitivity of the technique by up to 59%. Applications at rural study
      sites found some removal of FWCs in percolation areas of DWWTSs but they were
      still detectable 40 cm below the infiltration depth. FWCs were also detected as
      distinguishable peaks in impacted streams where septic tank effluents have a high
      contribution to the river flow.

PMID- 29035765
TI  - A force-based mechanistic model for describing activated sludge settling process.
AB  - Sludge settling as the last step in the biological wastewater treatment process
      substantially affects the system performance, and thus the design and control
      optimization of the sludge settling process has been frequently investigated with
      mathematical modeling tools. So far, these models are developed on the basis of
      the solid flux theory with numerous parameters and complicated boundary
      conditions, and their prediction results are often unsatisfactory. In this work,
      a new force-based mechanical model with five parameters was developed, in which
      five forces were adopted and Newton's law, rather than the flux theory, was used
      to describe the sludge settling process. In such a model, the phase interactions
      were taken into account. New functions of hydrodynamic drag, solids pressure and
      shear stress were developed. Model validation results demonstrate that both batch
      and continuous sludge settling processes could be accurately described by this
      model. The predictions of this model were more accurate than those of flux theory
      based models, suggesting its advantages in understanding sludge settling
      behaviors. In addition, this mechanistic model needed to input 5 parameters and
      set 1 boundary condition only, and could be directly executed by commercial
      computational fluid dynamics software. Thus, this force-based model provides a
      more convenient and useful tool to improve the activated sludge settling design
      and operation optimization.

PMID- 29035766
TI  - Sequential biofiltration - A novel approach for enhanced biological removal of
      trace organic chemicals from wastewater treatment plant effluent.
AB  - Recent studies revealed the benefits of oligotrophic and oxic conditions for the
      biological removal of many trace organic chemicals (TOrCs) during soil-aquifer
      treatment. These findings indicate an unused tuning potential that might also be
      applicable in engineered biofiltration systems with drastically reduced hydraulic
      retention times for an enhanced mitigation of TOrCs during wastewater treatment.
      This study introduces the novel approach of sequential biofiltration (SBF) for
      the advanced treatment of secondary effluent using two granular media filters
      operated in series with an intermediate aeration step aiming for oxic and
      oligotrophic conditions in the second filter stage. Results from the experiments
      conducted at pilot-scale confirm a reduced substrate availability and
      predominantly oxic conditions in the second filter stage of the SBF setup. An
      increased removal of several TOrCs was observed in an SBF system as compared to a
      conventional single-stage biofiltration unit operated at the same overall empty
      bed contact time (EBCT). Short-term tests with varying EBCTs in the first filter
      stage revealed a high degree of system robustness of TOrC mitigation when
      confronted with sudden hydraulic load variations. Higher removal of several TOrCs
      at increased EBCTs in the second filter stage indicates that EBCT might play a
      crucial role for the degradation of certain compounds.

PMID- 29035767
TI  - Life-cycle energy impacts for adapting an urban water supply system to droughts.
AB  - In recent years, cities in some water stressed regions have explored alternative
      water sources such as seawater desalination and potable water recycling in spite
      of concerns over increasing energy consumption. In this study, we evaluate the
      current and future life-cycle energy impacts of four alternative water supply
      strategies introduced during a decade-long drought in South East Queensland
      (SEQ), Australia. These strategies were: seawater desalination, indirect potable
      water recycling, network integration, and rainwater tanks. Our work highlights
      the energy burden of alternative water supply strategies which added
      approximately 24% life-cycle energy use to the existing supply system (with
      surface water sources) in SEQ even for a current post-drought low utilisation
      status. Over half of this additional life-cycle energy use was from the
      centralised alternative supply strategies. Rainwater tanks contributed an
      estimated 3% to regional water supply, but added over 10% life-cycle energy use
      to the existing system. In the future scenario analysis, we compare the life
      cycle energy use between "Normal", "Dry", "High water demand" and "Design
      capacity" scenarios. In the "Normal" scenario, a long-term low utilisation of the
      desalination system and the water recycling system has greatly reduced the energy
      burden of these centralised strategies to only 13%. In contrast, higher
      utilisation in the unlikely "Dry" and "Design capacity" scenarios add 86% and
      140% to life-cycle energy use of the existing system respectively. In the "High
      water demand" scenario, a 20% increase in per capita water use over 20 years
      "consumes" more energy than is used by the four alternative strategies in the
      "Normal" scenario. This research provides insight for developing more realistic
      long-term scenarios to evaluate and compare life-cycle energy impacts of drought
      adaptation infrastructure and regional decentralised water sources. Scenario
      building for life-cycle assessments of water supply systems should consider i)
      climate variability and, therefore, infrastructure utilisation rate, ii)
      potential under-utilisation for both installed centralised and decentralised
      sources, and iii) the potential energy penalty for operating infrastructure well
      below its design capacity (e.g., the operational energy intensity of the
      desalination system is three times higher at low utilisation rates). This study
      illustrates that evaluating the life-cycle energy use and intensity of these type
      of supply sources without considering their realistic long-term operating
      scenario(s) can potentially distort and overemphasise their energy implications.
      To other water stressed regions, this work shows that managing long-term water
      demand is also important, in addition to acknowledging the energy-intensive
      nature of some alternative water sources.

PMID- 29035768
TI  - UV photoconversion of environmental oestrogen diethylstilbestrol and its
      persistence in surface water under sunlight.
AB  - As one of the most oestrogenic synthetic compounds in water environment,
      diethylstilbestrol (DES) has been studied for decades. Some studies showed that
      DES can be removed by ultraviolet (UV) irradiation. However, no one has paid
      attention to the formation of oestrogenic disinfection by-products (DBPs) and the
      persistence of DES in surface water remains a mystery. In this study, UV was
      found to be very effective in removing oestrogenic activity regardless of water
      quality. Three oestrogenic DBPs were specifically isolated by oestrogen receptor
      based affinity chromatography and identified as 9,10-diethylphenanthrene-3,6
      diol, cis-DES and Z,Z-dienestrol. Among them, 9,10-diethylphenanthrene-3,6-diol
      was proved to have stronger oestrogenic activity than E2, but it can be further
      photodegraded. In addition, DES was also demonstrated to be a photochromic
      compound, whose UV-induced intermediates can be transformed back to DES under
      sunlight, which significantly slows down the photodegradation of DES. This study
      solves the question as to why UV-degradable DES is still detectable in the
      ambient water and provides a deep understanding of DES removal during UV
      disinfection.

PMID- 29035769
TI  - Transport and long-term release behavior of polymer-coated silver nanoparticles
      in saturated quartz sand: The impacts of input concentration, grain size and flow
      rate.
AB  - This study investigated the transport and long-term release of stabilized poly
      vinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) in a quartz sand column
      with various sand grain sizes (0.3-0.5 MUm, 0.5-1.0 MUm, 1.0-2.0 MUm), input
      concentrations of PVP-AgNP solution (1, 5, 15, 25 mg/L), and flow rates
      corresponding to a filter velocities (1.0, 1.5, 2.0, 2.5 mL/min-0.14, 0.21, 0.28,
      0.35 cm/min) by determining breakthrough curves, retention profiles, and long
      term release curves. Breakthrough curves and retention profiles were simulated by
      a mathematical model based on the advection dispersion equation coupled with
      second-order kinetics. The increased transport of PVP-AgNPs in quartz sand
      occurred with increased grain sizes and reduced input concentrations, and the
      transport can be predicted by the colloid filtration theory and DLVO theory. The
      long-term (one week) release amounts of retained PVP-AgNPs were 42.78%, 31.45%,
      and 10.95% in the fine, medium, and coarse sand columns, respectively, and were
      34.70%, 40.79%, 47.24%, and 57.32% at flow rates of 0.0363, 0.0436, 0.0545, and
      0.0726 mL/min, respectively. The released quantity of retained PVP-AgNPs
      decreased as the sand grain size increased. This phenomenon is opposite with the
      trend of increased transport of PVP-AgNPs with increased grain size in the
      transport test, which most likely because colloidal filtration regulates the
      transport process and adsorption (and desorption) dominates the release process.
      Increasing the flow rate increased the shear force on the particles, which
      improved the release of PVP-AgNPs. The results of the release tests further
      verified our previous published studies showing that the long-term release of
      retained PVP-AgNPs in the quartz sand was mostly in the form of released
      nanoparticles rather than ions. The results of this study indicated that sand
      grain size, input concentration, and flow rate have a prominent influence on the
      transport and long-term release behavior of PVP-AgNPs in saturated quartz sand.

PMID- 29035770
TI  - Solar desalination of seawater using double-dye-modified PTFE membrane.
AB  - The production of purified water by seawater desalination is now a significant
      countermeasure against recent severe water shortage. As the global warming is
      thought to be a dominant cause of the water scarcity problem, the energy employed
      for the desalination should be free from fossil fuels. We recently reported a
      simple membrane desalination combining the harvesting of solar energy and the
      membrane permeation of vaporized water. Water on a PTFE (polytetrafluoroethylene)
      membrane modified with disperse red 1 (DR1) as an azobenzene dye that photo
      isomerizes with visible light permeates through it under visible light
      irradiation. The penetrated water was efficiently desalinated to produce purified
      water by membrane distillation mechanism, where water was evaporated by DR1 using
      solar energy. In this paper, we report that the aqueous solution of rhodamine B
      on non modified PTFE membrane permeated the membrane to be purified under visible
      light irradiation. This paper also reports that a PTFE membrane modified with
      disperse blue 14 (DB14) was active for the desalination. Thus, even these non
      azobenzene dyes were revealed to be available for the light induce water
      permeation. When DR1 and DB14 were modified to PTFE membrane concurrently, a
      higher performance of seawater desalination using simulated sunlight was achieved
      by efficient absorption of the irradiated light with DR1 and DB14.

PMID- 29035771
TI  - Separation of peroxidases from Miscanthus x giganteus, their partial
      characterisation and application for degradation of dyes.
AB  - Due to wide applicative potential of peroxidases (POXs), the search for novel
      sources and forms, possibly with better characteristics and performances, is
      justified. In this study, POXs from Miscanthus x giganteus rhizomes grown in
      chernozem-like soil and mine tailings were examined. Higher activity of POXs in
      samples originating from the metal-contaminated soil was found. The quantity of
      acidic isoforms was much greater than basic. The rates of reactions catalysed by
      acidic POX isoforms decreased slightly at 50  degrees C, whereas stability of
      basic isoforms was affected at 40  degrees C. Concentrations of Zn, Mn and Fe
      were higher in rhizomes grown in mine tailings, and negatively correlated with
      the concentration of proteins. Basic POX isoforms effectively degraded CBB R250,
      while Amidoblack 10b was predominantly degraded by acidic isoforms. Thus,
      Miscanthus x giganteus can be used as a source of POXs which can be applied for
      dye decomposition and, possibly, waste water management.

PMID- 29035772
TI  - Effect of lignite on alleviation of salt toxicity in soybean (Glycine max L.)
      plants.
AB  - Salt toxicity of agricultural land is a natural phenomenon which is due to
      agricultural irrigation. This toxicity is harmful to crop productivity via
      increasing oxidative stress products. In a factorial controlled trial, four
      levels of lignite-enriched soil (soil lignite content: none, 50, 75 and 100 g kg
      1) were exposed to three levels of soil salinity (0, 5 and 10 dS m-1 NaCl). Then
      reactive oxygen species (ROS) generation (hydrogen peroxide and superoxide
      radical), lipid peroxidation, antioxidant enzymes activities (peroxidase,
      catalase and super oxide dismutase), proline, glycine betaine, soluble sugars and
      soluble protein contents of soybean plants were compared across different lignite
      concentration and saline toxicity. Under the 5 and 10 dS m-1 NaCl, sodium entry
      to the leaf and root cells, hydrogen peroxide concentration, superoxide radical
      generation, lipid peroxidation and osmoprotectants creation increased and
      consequently plant growth reduced (12-49%). Lignite applications by improving the
      cation exchange capacity of soil (8-16%), enriched the leaf and root cells with
      potassium (5-26%), calcium (40-56%), magnesium (30-42%) and inhibited the sodium
      entry to the cells, and consequently increased potassium/sodium ratio and reduced
      oxidative stress, antioxidant activities and synthesis of osmoprotectants in
      soybean leading to increased plant biomass (18-37%). Lignite usage in 75 and 100
      g kg-1 soil showed a better effect than 50 g kg-1 soil on reducing harmful
      effects of salt toxicity. Soil enrichment with lignite improves plant tolerance
      to salt toxicity via decreased oxidative stress.

PMID- 29035773
TI  - First Irish and tenth case of small bowel obstruction secondary to suprapubic
      catheterisation in the world. Case report and case review of a rare complication
      of suprapubic catheterisation.
AB  - INTRODUCTION: Percutaneous Suprapubic urinary bladder catheterisation (SPC) is a
      common procedure performed in cases of urinary retention where attempt to pass
      urethral catheter has failed. However, the procedure requires meticulous
      precision, vigilance and sound knowledge of anatomy, to avoid grave
      complications. We are reporting a very rare complication of Suprapubic
      catheterisation that is small bowel obstruction. Our case is first Irish and 10th
      global case of small bowel obstruction secondary to SPC. CASE PRESENTATION: Aim
      of this study was to report this rare complication of the SPC in our patient who
      was 88 years old retired farmer presenting to emergency department with small
      bowel obstruction. In our case after clinical examination diagnosis was made with
      CT scan. Laparoscopy done and found that SPC passed through mesentery before
      entering bladder and was released laparoscopically. We also searched the
      literature to find similar reported cases to extract useful information from
      these cases and use this information to draw conclusions and make recommendations
      to avoid injuries in the future. Database search conducted in March 2017 on the
      bibliographic databases Ovid MEDLINE (1946 to November 2016) and EMBASE (1980 to
      November 2016) along with additional reference searching revealed only 9 reported
      cases of small bowel obstruction secondary to SPC. CONCLUSIONS: From the
      extensive literature search we found that there are only nine cases reported so
      far globally, and our case is first Irish and tenth international case of bowel
      obstruction secondary to SPC. Significantly distended bladder, use of ultrasound
      and extra precaution in elderly patients can reduce the risk of damage to bowel.

PMID- 29035774
TI  - Facial dog bite injuries in children: A case report.
AB  - INTRODUCTION: Dog bites are common and can affect victims of different ages, from
      children to the elderly. Injuries are usually located in different body regions,
      including head and face. The treatment of choice for injuries is the suture of
      the lesion, accompanied by antibiotic therapy and tetanus and anti-rabies
      vaccination. PRESENTATION OF CASE: An 11-year-old male black patient was admitted
      to the Surgery and Maxillo-Facial Traumatology Service, on an urgent basis,
      victim of domestic animal aggression (dog biting). The child had multiple and
      extensive lesions on the face, trauma with laceration with loss of substance,
      involving the left genic region, lower and upper lip, and lower gingival-labial
      sulcus. DISCUSSION: Smaller children are especially vulnerable to injuries in the
      craniofacial region due their low stature, propensity to crawl/play on the ground
      and exploratory behavior. The primary treatment of bites is by means of direct
      suture, grafting or local flaps, depending on the type of wound and the surgeon's
      decision, regardless of time elapsed from the attack. CONCLUSION: This case shows
      a case of a child patient victim of animal bite, with lesions limited to the
      region of the face. The patient was followed up for a month and showed good wound
      healing without any complications.

PMID- 29035775
TI  - Avoiding the pocket: A case report of coiling of distal shunt catheter into
      subcutaneous pocket.
AB  - INTRODUCTION: Hydrocephalus is one of the most common disorders of neurosurgery
      and ventricular shunting, the primary surgical intervention, malfunctions in 85%
      of patients by 10 years. PRESENTATION OF CASE: Here we present a case of a 12
      year-old girl with history of a vagal nerve stimulator (VNS) and ventricular
      shunt, most recently revised from ventriculoatrial (VA) to ventriculoperitoneal
      (VP) shunt at an outside hospital. The patient presented with a new left chest
      bulge, nausea, emesis, and seizures. Imaging revealed the patient's distal shunt
      catheter to have completely migrated and coiled into the VNS subcutaneous pocket.
      Subsequently, the patient's distal shunt catheter was externalized, and later
      internalized back to a VA shunt. DISCUSSION: Potential spaces from previous
      surgeries such as VNS can lead to coiling of distal shunt catheters. In this
      case, the coiled distal shunt catheter led to hydrocephalus and the patient's
      presenting symptoms. CONCLUSION: It is imperative to recognize patients with
      previous surgeries, especially those involving subcutaneous implants and to avoid
      passing of distal shunt catheters through these potential spaces.

PMID- 29035776
TI  - Dammarane-type saponins from the leaves of Panax notoginseng and their
      neuroprotective effects on damaged SH-SY5Y cells.
AB  - Seven dammarane-type saponins previously undescribed (notoginsenosides Fh1-Fh7)
      were isolated from the aqueous extract leaves of Panax notoginseng (Burk.)
      F.H.Chen (Araliaceae), together with eleven known saponins. Their structures of
      were elucidated by spectroscopic analysis (NMR, UV, IR, ect.), HR-ESI-MS
      techniques and chemical methods. Screening results indicated that compounds 4, 5,
      12, 13 showed moderate neuroprotective effects on H2O2-induced cellular damage in
      human neuroblastoma SH-SY5Y cells (10 MUM).

PMID- 29035777
TI  - Investigation of the composition-structure-property relationship of AsxTe100-x
      films prepared by plasma deposition.
AB  - AsxTe100-x amorphous films of different chemical content were prepared by Plasma
      Enhanced Chemical Vapor Deposition (PECVD). For the first time the optical
      properties of As-Te chalcogenide materials have been measured in UV-VIS-IR ranges
      (from 0.2 to 25MUm) for a very wide range of chemical compositions (20-80at.%
      As). As-Te films have been tuned from 0.80 to 1.10eV. The IR results obtained
      have been juxtaposed with the Raman spectroscopy findings to establish the
      correlation between optical and structural properties of the materials developed.
      Reversible and irreversible changes in the phase composition of the As-Te films
      under annealing of the surface by laser irradiation have been demonstrated and
      studied. In order to determine the potential areas of application of the prepared
      As-Te films the thermal and photo sensitivity has been also investigated.

PMID- 29035778
TI  - The 'over-researched community': An ethics analysis of stakeholder views at two
      South African HIV prevention research sites.
AB  - Health research in resource-limited, multi-cultural contexts raises complex
      ethical concerns. The term 'over-researched community' (ORC) has been raised as
      an ethical concern and potential barrier to community participation in research.
      However, the term lacks conceptual clarity and is absent from established ethics
      guidelines and academic literature. In light of the concern being raised in
      relation to research in low- and middle-income countries (LMICs), a critical and
      empirical exploration of the meaning of ORC was undertaken. Guided by Emanuel et
      al.'s (2004) eight principles for ethically sound research in LMICs, this study
      examines the relevance and meaning of the terms 'over-research' and 'over
      researched community' through an analysis of key stakeholder perspectives at two
      South African research sites. Data were collected between August 2007 and October
      2008. 'Over-research' was found to represent a conglomeration of ethical concerns
      often used as a proxy for standard research ethics concepts. 'Over-research'
      seemed fundamentally linked to disparate positions and perspectives between
      different stakeholders in the research interaction, arising from challenges in
      inter-stakeholder relationships. 'Over-research' might be interpreted to mean
      exploitation. However, exploitation itself could mean different things. Using the
      term may lead to obscured understanding of real or perceived ethical concerns,
      making it difficult to identify and address the underlying concerns. It is
      recommended that the term be carefully and critically interrogated for clarity
      when used in research ethics discourse. Because it represents other legitimate
      concerns, it should not be dismissed without careful exploration.

PMID- 29035779
TI  - Data-driven heterogeneity in mathematical learning disabilities based on the
      triple code model.
AB  - Many classifications of heterogeneity in mathematical learning disabilities (MLD)
      have been proposed over the past four decades, however no empirical research has
      been conducted until recently, and none of the classifications are derived from
      Triple Code Model (TCM) postulates. The TCM proposes MLD as a heterogeneous
      disorder, with two distinguishable profiles: a representational subtype and a
      verbal subtype. A sample of elementary school 3rd to 6th graders was divided into
      two age cohorts (3rd - 4th grades, and 5th - 6th grades). Using data-driven
      strategies, based on the cognitive classification variables predicted by the TCM,
      our sample of children with MLD clustered as expected: a group with
      representational deficits and a group with number-fact retrieval deficits. In the
      younger group, a spatial subtype also emerged, while in both cohorts a non
      specific cluster was produced whose profile could not be explained by this
      theoretical approach.

PMID- 29035780
TI  - Long non-coding RNAs in the atherosclerotic plaque.
AB  - BACKGROUND AND AIMS: Genetic and environmental factors are important components
      of the development of atherosclerosis. Long non-coding RNA (lncRNAs) have emerged
      as regulators of multiple pathophysiological pathways in the cardiovascular
      system. Here, we investigated potential associations between lncRNAs and
      atherosclerosis. METHODS: Tissue samples from atherosclerotic coronary artery
      plaques and non-atherosclerotic internal mammary artery were obtained from 20
      patients during coronary artery bypass surgery. Expression levels of five lncRNAs
      known to be associated with coronary artery disease were measured using
      quantitative PCR. RESULTS: Cyclin-dependent kinase inhibitor 2B antisense RNA 1
      (ANRIL) and myocardial infarction-associated transcript (MIAT) were more
      expressed in the atherosclerotic arteries compared to the non-atherosclerotic
      arteries. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was
      less expressed in the atherosclerotic plaques. Expression levels of potassium
      voltage-gated channel, KQT-like subfamily, member 1 opposite strand/antisense
      transcript 1 (KCNQ1OT1) and hypoxia inducible factor 1A antisense RNA 2 (aHIF)
      were comparable between atherosclerotic and non-atherosclerotic arteries. In the
      atherosclerotic plaque, expression levels of MALAT1, MIAT, KCNQ1OT1 and aHIF were
      inversely correlated with age. CONCLUSIONS: We report significant associations
      between lncRNAs and atherosclerosis. These findings support a role for lncRNAs in
      coronary artery disease development.

PMID- 29035782
TI  - Opposing effects of rheumatoid arthritis and low dose prednisolone on arginine
      metabolomics.
AB  - BACKGROUND AND AIMS: The effects of low dose prednisolone on circulating markers
      of endothelial function, the arginine metabolites asymmetric dimethyl arginine
      (ADMA), mono methyl arginine (MMA), and homoarginine, are uncertain. We assessed
      whether patients with rheumatoid arthritis have perturbations in arginine
      metabolite concentrations that are reversed by low dose prednisolone. METHODS:
      Eighteen rheumatoid arthritis patients who had not taken prednisolone for >6
      months (non-glucocorticoid (GC) users), 18 rheumatoid arthritis patients taking
      continuous oral prednisolone (6.5 +/- 1.8 mg/day) for >6 months (GC users) and 20
      healthy controls were studied. Fasting plasma concentrations of ADMA, MMA, and
      homoarginine were measured by ultra-performance liquid-chromatography. Baseline
      data from non-GC users were compared with healthy controls to assess the effect
      of rheumatoid arthritis. The change in arginine metabolites in non-GC users after
      7 days of prednisolone (6 mg/day) was used to assess the acute effects of
      prednisolone. Baseline data from non-GC users were compared with GC users to
      assess the chronic effects of prednisolone. RESULTS: Non-GC users had higher ADMA
      (0.59 +/- 0.03 vs. 0.47 +/- 0.01 MUM, p = 0.004) and MMA concentrations (0.10 +/-
      0.01 vs. 0.05 +/- 0.00 MUM, p < 0.001) than controls. The only change with acute
      prednisolone was a reduction in homoarginine (1.23 +/- 0.06 vs. 1.08 +/- 0.06
      MUM, p = 0.04) versus baseline. GC users had lower concentrations of ADMA (0.51
      +/- 0.02 vs. 0.59 +/- 0.03 MUM, p = 0.03) than non-GC users. CONCLUSIONS:
      Rheumatoid arthritis patients have higher concentrations of ADMA and MMA,
      inhibitors of endothelial function. Chronic, but not acute, prednisolone therapy
      is associated with a lower ADMA concentration, suggesting a salutary effect of
      long-term glucocorticoid treatment on endothelial function.

PMID- 29035783
TI  - Radiotracer investigation on the measurement of residence time distribution in an
      ethyl acetate reactor system with a large recycle ratio.
AB  - A radiotracer investigation was carried out on the measurement of residence time
      distribution (RTD) of process fluid in an industrial-scale ethyl acetate reactor
      system, which consists of two independent reactors with recirculation and
      connected in series with each other. Bromine-82 as ammonium bromide was used as
      the radiotracer for the RTD experiments at different operating conditions. The
      individual reactors and the overall reactor system were modelled using physically
      representative phenomenological models comprising of continuously stirred tank
      reactors (CSTRs). The results showed that the recirculation rate considerably
      affected the flow mixing behaviour and mean residence time of the process fluid
      in the reactor system. The results also showed that there was bypassing of the
      fluid in the first reactor that ranged from 12% to 22% and 40% dead volume at
      different operating conditions, whereas the second reactor behaved closely as an
      ideal CSTR. The results of the investigation can be used to optimise the process
      parameters and design new improved reactor systems for the production of ethyl
      acetate.

PMID- 29035781
TI  - Lack of myeloid Fatp1 increases atherosclerotic lesion size in Ldlr-/- mice.
AB  - BACKGROUND AND AIMS: Altered metabolism is an important regulator of macrophage
      (MPhi) phenotype, which contributes to inflammatory diseases such as
      atherosclerosis. Broadly, pro-inflammatory, classically-activated MPhis (CAM) are
      glycolytic while alternatively-activated MPhis (AAM) oxidize fatty acids,
      although overlap exists. We previously demonstrated that MPhi fatty acid
      transport protein 1 (FATP1, Slc27a1) was necessary to maintain the oxidative and
      anti-inflammatory AAM phenotype in vivo in a model of diet-induced obesity. The
      aim of this study was to examine how MPhi metabolic reprogramming through FATP1
      ablation affects the process of atherogenesis. We hypothesized that FATP1 limits
      MPhi-mediated inflammation during atherogenesis. Thus, mice lacking MPhi Fatp1
      would display elevated formation of atherosclerotic lesions in a mouse model
      lacking the low-density lipoprotein (LDL) receptor (Ldlr-/-). METHODS: We
      transplanted bone marrow collected from Fatp1+/+ or Fatp1-/- mice into Ldlr-/-
      mice and fed chimeric mice a Western diet for 12 weeks. Body weight, blood
      glucose, and plasma lipids were measured. Aortic sinus and aorta lesions were
      quantified. Atherosclerotic plaque composition, oxidative stress, and
      inflammation were analyzed histologically. RESULTS: Compared to Fatp1+/+Ldlr-/-
      mice, Fatp1-/-Ldlr-/- mice exhibited significantly larger lesion area and
      elevated oxidative stress and inflammation in the atherosclerotic plaque.
      Macrophage and smooth muscle cell content did not differ by Fatp1 genotype. There
      were no significant systemic alterations in LDL, high-density lipoprotein (HDL),
      total cholesterol, or triacylglyceride, suggesting that the effect was local to
      the cells of the vessel microenvironment in a Fatp1-dependent manner.
      CONCLUSIONS: MPhi Fatp1 limits atherogenesis and may be a viable target to
      metabolically reprogram MPhis.

PMID- 29035784
TI  - Concentrations of Staphylococcus species in indoor air as associated with other
      bacteria, season, relative humidity, air change rate, and S. aureus-positive
      occupants.
AB  - The aim of this study was to obtain knowledge about concentrations of
      Staphylococcus aureus, MRSA (methicillin-resistant S. aureus), and other
      Staphylococcus species in indoor air in Greater Copenhagen and about factors
      affecting the concentrations. The effects of season, temperature, relative
      humidity, air change rate (ACR), other bacterial genera, area per occupant, and
      presence of S. aureus-positive occupants were studied. In samples from 67 living
      rooms, S. hominis, S. warneri, S. epidermidis, and S. capitis were found in 13
      25%; S. saprophyticus, S. cohnii, and S. pasteuri in 5-10%; and S. lugdunensis,
      S. haemolyticus, S. caprae, S. equorum, S. kloosii, S. pettenkoferi, S. simulans,
      and S. xylosus in less than 3%. Staphylococcus aureus were found in two of 67
      living rooms: spa type t034 (an MRSA) was recovered from a farmhouse, while spa
      type t509 was found in an urban home. Two species, S. equorum and S. kloosii,
      were found only in the farmhouse. Staphylococcus was significantly associated
      with season with lowest concentration and richness in winter. Genera composition
      was associated with ACR with smaller fractions of Staphylococcus at higher ACR,
      while richness was significantly and negatively associated with area per
      occupant. Concentration of Staphylococcus correlated positively with the total
      concentration of bacteria, but negatively with the total concentration of other
      bacteria. The concentration of Staphylococcus was not significantly associated
      with concentrations of the other abundant genera Bacillus, Kocuria, and
      Micrococcus. In offices with S. aureus-positive occupants, airborne S. aureus was
      not found. In conclusion, Staphylococcus species constitute a considerable
      proportion of the airborne bacteria in the studied homes and offices. However,
      both S. aureus and MRSA had very low prevalence during all seasons. Thus,
      transmission of S. aureus and MRSA through the air in living rooms in Copenhagen
      is expected to be limited. The negative associations between ACR and the fraction
      Staphylococcus constituted out of total bacteria, and between area per occupant
      and Staphylococcus richness indicate that it might be possible to affect the
      presence of airborne Staphylococcus in homes.

PMID- 29035785
TI  - Association of blood polychlorinated biphenyls and cholesterol levels among
      Canadian Inuit.
AB  - BACKGROUND: It has generally been thought that Inuit populations have low risk of
      cardiovascular disease due to high consumption of omega-3 fatty acids found in
      traditional marine-based diets. However, results of recent surveys showed that
      Inuit populations are experiencing increasing rates of cardiovascular disease and
      related risk factors. OBJECTIVE: The purpose of this study was to investigate if
      blood polychlorinated biphenyls (PCBs) are associated with high cholesterol and
      related parameters in Canadian Inuit, known risk factors for cardiovascular
      disease. METHODS: The Adult Inuit Health Survey (IHS, 2007-2008) included 2595
      Inuit participants from three regions of the Canadian Arctic, of which 2191 could
      be classified as with or without high cholesterol. The high cholesterol outcome
      was defined by LDL-C > 3.36mmol/L or taking medication(s) that reduce
      cholesterol, and was examined in adjusted logistic regression models with
      individual blood levels of PCB congeners, sum of dioxin-like PCBs (?DL-PCBs), or
      sum of non-dioxin-like PCBs (?NDL-PCBs). Statistically significant covariates for
      high cholesterol were ranked in importance according to the proportion of the
      model log likelihood explained. Continuous clinical parameters of total
      cholesterol, triglycerides, LDL-C, and HDL-C were examined in multiple linear
      regression models with ?DL-PCBs or ?NDL-PCBs. RESULTS: A total of 719
      participants had high cholesterol (32.8%). PCBs were associated with increased
      risk of high cholesterol, and higher levels of serum triglycerides, total
      cholesterol, and LDL-C. No association was observed between PCBs and serum HDL-C.
      With respect to other statistically significant covariates for high cholesterol,
      the log likelihood ranking of PCBs generally fell between body mass index (BMI)
      and age. CONCLUSION: Further work is needed to corroborate the associations
      observed with PCBs and lipids in Canadian Inuit and to examine if they are causal
      in the direction anticipated.

PMID- 29035786
TI  - Comparative transcriptome analysis reveals networks of genes activated in the
      whitefly, Bemisia tabaci when fed on tomato plants infected with Tomato yellow
      leaf curl virus.
AB  - The whitefly Bemisia tabaci can transmit hundreds of viruses to numerous
      agricultural crops in the world. Five genera of viruses, including Begomovirus
      and Crinivirus, are transmitted by B. tabaci. There is little knowledge about the
      genes involved in virus acquisition and transmission by whiteflies. Using a
      comparative transcriptomics approach, we evaluated the gene expression profiles
      of whiteflies (B. tabaci MEAM1) after feeding on tomato infected by a
      begomovirus, Tomato yellow leaf curl virus (TYLCV), in comparison to a recent
      study, in which whiteflies were fed on tomato infected by the crinivirus, Tomato
      chlorosis virus (ToCV). The data revealed similar temporal trends in gene
      expression, but large differences in the number of whitefly genes when fed on
      TYLCV or ToCV-infected tomato. Transcription factors, cathepsins, receptors, and
      a hemocyanin gene, which is implicated in mediating antiviral immune responses in
      other insects and possibly virus transmission, were some of the genes identified.

PMID- 29035787
TI  - Identification of N-linked glycosylation sites in the spike protein and their
      functional impact on the replication and infectivity of coronavirus infectious
      bronchitis virus in cell culture.
AB  - Spike (S) glycoprotein on the viral envelope is the main determinant of
      infectivity. The S protein of coronavirus infectious bronchitis virus (IBV)
      contains 29 putative asparagine(N)-linked glycosylation sites. These post
      translational modifications may assist in protein folding and play important
      roles in the functionality of S protein. In this study, we used bioinformatics
      tools to predict N-linked glycosylation sites and to analyze their distribution
      in IBV strains and variants. Among these sites, 8 sites were confirmed in the S
      protein extracted from partially purified virus particles by proteomics
      approaches. N-D and N-Q substitutions at 13 predicted sites were introduced into
      an infectious clone system. The impact on S protein-mediated cell-cell fusion,
      viral recovery and infectivity was assessed, leading to the identification of
      sites essential for the functions of IBV S protein. Further characterization of
      these and other uncharacterized sites may reveal novel aspects of N-linked
      glycosylation in coronavirus replication and pathogenesis.

PMID- 29035788
TI  - Coronavirus infectious bronchitis virus non-structural proteins 8 and 12 form
      stable complex independent of the non-translated regions of viral RNA and other
      viral proteins.
AB  - The cleavage products from coronavirus polyproteins, known as the non-structural
      proteins (nsps), are believed to make up the major components of the viral
      replication/transcription complex. In this study, several nsps encoded by avian
      gammacoronavirus infectious bronchitis virus (IBV) were screened for RNA-binding
      activity and interaction with its RNA-dependent RNA polymerase, nsp12. Nsp2,
      nsp5, nsp8, nsp9 and nsp10 were found to bind to untranslated regions (UTRs),
      while nsp8 was confirmed to interact with nsp12. Nsp8 has been reported to
      interact with nsp7 and functions as a primase synthesizing RNA primers for nsp12.
      Further characterization revealed that nsp8-nsp12 interaction is independent of
      the UTRs of viral RNA, and nsp8 interacts with both the N- and C-terminal regions
      of nsp12. These results have prompted a proposal of how the nsp7-nsp8 complex
      could possibly function in tandem with nsp12, forming a highly efficient complex
      that could synthesize both the RNA primer and viral RNA during coronavirus
      infection.

PMID- 29035789
TI  - An easy way to detect dengue virus using nanoparticle-antibody conjugates.
AB  - The aim of the present research is to propose a new method based on localized
      surface plasmon resonance (LSPR) for fast dengue virus detection. A pool with
      four dengue serotypes (DENV-1, -2, -3, -4) was detected through antigen-antibody
      binding using gold nanoparticles (AuNPs) as signaling antibody carriers. Such
      result was confirmed through surface plasmon resonance (SPR), transmission
      electron microcopy (TEM), and dynamic light scattering (DLS) techniques. The
      limit of detection was calculated for TCID50 107 demonstrating a linear
      correlation between viral concentration and number of cells with an r2 value of >
      0.993. The assay presented good sensibility and reproducibility of results and
      the negative controls were not mistakenly detected. This design requires no
      pretreatment or high trained person. In the future, it can be used in commercial
      antibody detection kits.

PMID- 29035790
TI  - Is ecological food also radioecological? - 210Po and 210Pb studies.
AB  - Presented are results of a study on accumulation of naturally occurring 210Po and
      210Pb in ecological and conventional farming food products in Poland: fruits,
      vegetables and cereals. The main idea behind this research was to determine the
      activity concentrations of 210Po and 210Pb in ecological and commercial food as
      well as calculate and compare the effective dose (radiation) connected to
      different origin of analyzed food products consumption. The studies showed the
      majority of all compared food samples contained similar 210Po and 210Pb
      activities and statistically, the consumption of organic and commercial food
      would give similar annual effective dose.

PMID- 29035791
TI  - Availability of polycyclic aromatic hydrocarbons to earthworms in urban soils and
      its implications for risk assessment.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a global problem, and in urban soils
      they can be found at potentially hazard levels. Nevertheless, the real risks that
      these contaminants pose to the environment are not well known, since the
      bioavailability of PAHs in urban soils has been poorly studied. Therefore, the
      bioavailability of PAHs in some selected urban soils from Lisbon (Portugal) was
      evaluated. Moreover, the applicability of a first screening phase based on total
      contents of PAHs was assessed. Results show that bioavailability of PAHs is
      reduced (low levels in earthworms, low accumulation percentages, and low biota-to
      soil accumulation factors values), especially in more contaminated soils. The
      aging of these compounds explains this low availability, and confirms the
      generally accepted assumption that accumulation of PAHs in urban areas is mostly
      related with a long-term deposition of contaminated particles. The comparison of
      measured PAHs concentrations in earthworm tissues with the ones predicted based
      on theoretical models, reinforce that risks based on total levels are
      overestimated, but it can be a good initial approach for urban soils. This study
      also highlights the need of more reliable ecotoxicological data.

PMID- 29035792
TI  - Evolution of consciousness of exposure to siloxanes-review of publications.
AB  - The purpose of this description is to review scientific literature from 1944 to
      2017 as a source of information on the reasons for the increased interest in
      siloxanes (silicones). Not only the research area, but first, the changes in the
      tendency of research aims are important issues in the evaluation. On the one
      hand, the authors emphasize the unique properties of linear and cyclic siloxanes,
      providing many examples of beneficial applications, and on the other hand, there
      are some warnings of overcoming of the safety barrier of their presence in human
      environment. Analyzing the results from the SCOPUS database, it can be argued
      that the increased interest of scientists and government agencies particularly
      relates to the analysis of siloxanes in biological and environmental samples.
      This is caused not only by the widespread use of various siloxanes in the
      pharmaceutical, medical, cosmetic and food industries, but also by the direct
      contact of these compounds with tissues, as well as an increased access to
      knowledge and modern research tools that have developed the awareness of hazards.
      The development of research methods enables not only constant monitoring of
      progressively lower siloxanes concentrations in various samples, but because of
      the specificity of these methods, it also enables an identification of specific
      siloxane compounds and evaluation of their effects on humans and environment.
      This paper discusses the issues of the evolution of consciousness of exposure to
      siloxanes due to their increased synthesis and widespread use in many areas of
      human life, which contributes to environmental pollution.

PMID- 29035793
TI  - Assessment of potential bioavailability of heavy metals in the sediments of land
      freshwater interfaces by diffusive gradients in thin films.
AB  - It is important to understand the potential bioavailability of heavy metals in
      the sediments of land-freshwater interfaces (between terrestrial and aquatic
      ecosystems). Therefore, we evaluated the pollution of Cr, Ni, Cu, Zn, As, and Cd
      in land-freshwater interface sediments/soils according to total concentrations,
      and used sequential extraction method to measure different fractions of Cd. Then,
      the diffusive gradients in thin films (DGT) technique was employed to study the
      potential bioavailability of metals. Results showed that the concentrations of
      exchangeable and weak acid soluble fraction and oxidizable fraction were higher
      in ecotone area, and the values of reducible fraction and residual fraction were
      higher in deep water area. There existed significant positive correlations
      between [Cd]-DGT (concentration of Cd measured by DGT) and EXC-Cd (exchangeable
      and weak acid soluble fraction of Cd) (r2 = 0.65), but the significant negative
      correlation was found between [Cd]-DGT and RES-Cd (Residual fraction of Cd) (r2 =
      0.52). DGT technique is a feasible method to measure potential bioavailability of
      heavy metals for risk assessment in the sediments/soils of land-freshwater
      interfaces.

PMID- 29035794
TI  - Role of adsorption in combined membrane fouling by biopolymers coexisting with
      inorganic particles.
AB  - This study was conducted in order to obtain a better understanding of the
      combined fouling by biopolymers coexisting with inorganic particles from the
      aspects of fouling index, fouling layer structure and biopolymer-particle
      interactions. Calcium alginate was used as the model biopolymer and Fe2O3, Al2O3,
      kaolin, and SiO2 were used as model inorganic particles. Results showed that the
      combined fouling differed greatly among the four types of inorganic particles.
      The differences were attributed particularly to the different adsorption
      capacities for calcium alginate by the particles with this capacity decreasing in
      the order of Fe2O3, Al2O3, kaolin and SiO2. Particle size measurement and
      electron microscopic observation indicated the formation of agglomerates between
      calcium alginate and those inorganic particles exhibiting strong adsorption
      capacity. A structure was proposed for the combined fouling layer comprised of a
      backbone cake layer of alginate-inorganic particle agglomerates with the pores
      partially filled with discontinuous calcium alginate gels. The filterability of
      the fouling layer was primarily determined by the abundance of the gels. The
      strength of physical interaction between calcium alginate and each type of
      inorganic particle was calculated from the respective surface energies and zeta
      potentials. Calculation results showed that the extent of physical interaction
      increased in the order of Al2O3, Fe2O3, kaolin and SiO2, with this order
      differing from that of adsorption capacity. Chemical interactions may also play
      an important role in the adsorption of alginate and the consequent combined
      fouling. High-resolution XPS scans revealed a slight shift of electron binding
      energies when alginate was adsorbed.

PMID- 29035795
TI  - Can poly-parameter linear-free energy relationships (pp-LFERs) improve modelling
      bioaccumulation in fish?
AB  - A wide range of studies have characterized different types of biosorbent, with
      regard to their interactions with chemicals. This has resulted in the development
      of poly-parameter linear free energy relationships (pp-LFERs) for the estimation
      of partitioning of neutral organic compounds to biological phases (e.g., storage
      lipids, phospholipids and serum albumins). The aims of this study were to explore
      and evaluate the influence of implementing pp-LFERs both into a one-compartment
      fish model and a multi-compartment physiologically based toxicokinetic (PBTK)
      fish model and the associated implications for chemical risk assessment. For this
      purpose, fish was used as reference biota, due to their important role in aquatic
      food chains and dietary exposure to humans. The bioconcentration factor (BCF) was
      utilized as the evaluation metric. Overall, our results indicated that models
      incorporating pp-LFERs (R2 = 0.75) slightly outperformed the single parameter
      (sp) LFERs approach in the one-compartmental fish model (R2 = 0.72). A pronounced
      enhancement was achieved for compounds with log KOW between 4 and 5 with
      increased R2 from 0.52 to 0.71. The minimal improvement was caused by the
      overestimation of lipid contribution and underestimation of protein contribution
      by the sp-approach, which cancelled each other out. Meanwhile, a greater
      improvement was observed for multi-compartmental PBTK models with consideration
      of metabolism, making all predictions fall within a factor of 10 compared with
      measured data. For screening purposes, the KOW-based (sp-LFERs) approach should
      be sufficient to quantify the main partitioning characteristics. Further
      developments are required for the consideration of ionization and more accurate
      quantification of biotransformation in biota.

PMID- 29035796
TI  - Characterization of iron and manganese minerals and their associated microbiota
      in different mine sites to reveal the potential interactions of microbiota with
      mineral formation.
AB  - Different environmental conditions such as pH and dissolved elements of mine
      stream induce precipitation of different minerals and their associated microbial
      community may vary. Therefore, mine precipitates from various environmental
      conditions were collected and their associated microbiota were analyzed through
      metagenomic DNA sequencing. Various Fe and Mn minerals including ferrihydrite,
      schwertmannite, goethite, birnessite, and Mn-substituted delta-FeOOH (delta-(Fe1
      x, Mnx)OOH) were found in the different environmental conditions. The Fe and Mn
      minerals were enriched with toxic metal(loid)s including As, Cd, Ni and Zn,
      indicating they can act as scavengers of toxic metal(loid)s in mine streams.
      Under acidic conditions, Acidobacteria was dominant phylum and Gallionella (Fe
      oxidizing bacteria) was the predominant genus in these Fe rich environments.
      Manganese oxidizing bacteria, Hyphomicrobium, was found in birnessite forming
      environments. Leptolyngbya within Cyanobacteria was found in Fe and Mn oxidizing
      environments, and might contribute to Fe and Mn oxidation through the production
      of molecular oxygen. The potential interaction of microbial community with
      minerals in mine sites can be traced by analysis of microbial community in
      different Fe and Mn mineral forming environments. Iron and Mn minerals contribute
      to the removal of toxic metal(loid)s from mine water. Therefore, the
      understanding characteristics of mine precipitates and their associated microbes
      helps to develop strategies for the management of contaminated mine water.

PMID- 29035797
TI  - Effects of GAC layer on the performance of gravity-driven membrane filtration
      (GDM) system for rainwater recycling.
AB  - Gravity-driven membrane filtration (GDM) is promising for decentralized rainwater
      recycling, owing to low maintenance and energy consumption. However, the organic
      removal by GDM process is sometimes undesirable and the quality of the permeate
      cannot meet the standard of water reuse. To improve this, granular activate
      carbon (GAC) was added as a particle layer on the membrane surface of GDM system.
      Additionally, a system with sand addition and a system with no particle addition
      were trialed as comparisons, to study the combined effects of particle hindering
      and adsorption on the removal efficacy of organics and the development of
      permeate flux. Results showed that GDM with a GAC layer improved removal
      efficiency of organics by 25%, and that GAC enhanced removal of florescent
      compounds (e.g., aromatic proteins, tryptophan proteins and humics), compared
      with the other two systems. Additionally, the permeate flux in three systems
      stabilized after Day 25, and kept stable until the end of the operation. However,
      the presence of GAC layer decreased the level of stable flux (3.2 L/m2h) compared
      with the control system (4.5 L/m2h). The factors responsible for the lower flux
      and severe membrane fouling in GAC layer assisted system were the combined
      effects of particle and adsorption which led to a denser bio-fouling layer with
      higher amount of biomass and extracellular polymeric substances contents
      (proteins and polysaccharides). Resistance distribution analyses revealed that
      GAC layer mainly increased hydraulically reversible resistance (occupied 93%) of
      the total resistance, indicating that the flux could be recovered easily by
      simple physical cleaning.

PMID- 29035798
TI  - Sexual function and related factors in Iranian woman with epilepsy.
AB  - PURPOSE: Epileptic women are faced with many sexual challenges in their life due
      to medical and non-medical factors. The present study was conducted to assess
      sexual function in epileptic women and its related factors. METHOD: The present
      cross-sectional study was conducted on 196 epileptic married women of
      reproductive age who were members of the Iranian Epilepsy Association and were
      selected continuously over six months through convenience sampling. The data
      collection tools included the Female Sexual Function Index (FSFI) and questions
      about the causes of sexual dysfunction. The statistical tests including: Chi
      square, t-test, one-way ANOVA, linear and logistic regression. RESULTS: According
      to the results, 74.5% of the participants suffered from sexual dysfunction and
      scored the lowest in terms of the orgasm and sexual satisfaction dimensions. The
      factors associated with sexual dysfunction included age over 40, poor education,
      more than 15 years of marriage, poor economic status, history of infertility and
      irregular menstruation, several seizures per month, nocturnal seizures, triple or
      multiple drug therapies and not using anticonvulsant drugs that have no effect on
      the liver enzymes. From participants' perspective, the most common causes of
      sexual dysfunction include anxiety and stress, emotional problems with the
      spouse, dissatisfaction with the experience of unwanted sex and the type of drugs
      used. CONCLUSIONS: Since the incidence of sexual dysfunction in epileptic women
      is high and multifactorial, it is recommended for experts and health service
      providers to not only seek to better control the patients' seizures, but also
      assess them in terms sexual function.

PMID- 29035799
TI  - Use of the endometriosis fertility index in daily practice: A prospective
      evaluation.
AB  - OBJECTIVE: To perform a prospective evaluation of postoperative fertility
      management using the endometriosis fertility index (EFI). STUDY: This prospective
      non-interventional observational study was performed from January 2013 to
      February 2016 in a tertiary care university hospital and an assisted reproductive
      technology (ART) centre. In total, 196 patients underwent laparoscopic surgery
      for endometriosis-related infertility. Indications for surgery included pelvic
      pain (dysmenorrhoea, and/or deep dyspareunia), abnormal hysterosalpingogram, and
      failure to conceive after three or more superovulation cycles with or without
      intra-uterine insemination. Multidisciplinary fertility management followed the
      surgical diagnosis and treatment of endometriosis. Three postoperative options
      were proposed to couples based on the EFI score: EFI score <=4, ART (Option 1);
      EFI score 5-6, non-ART management for 4-6 months followed by ART (Option 2); or
      EFI score >=7, non-ART management for 6-9 months followed by ART (Option 3). The
      main outcomes were non-ART pregnancy rates and cumulative pregnancy rates
      according to EFI score. Univariate and multivariate analyses with backward
      stepwise logistic regression were used to explain the occurrence of non-ART
      pregnancy after surgery for women with EFI scores >=5. Adjustment was made for
      potential confounding variables that were significant (p<0.05) or tending towards
      significance (p<0.1) on univariate analysis. RESULTS: The cumulative pregnancy
      rate was 76%. The total number of women and pregnancy rates for Options 1, 2 and
      3 were: 26 and 42.3%; 56 and 67.9%; and 114 and 87.7%, respectively. The non-ART
      pregnancy rates for Options 1, 2 and 3 were 0%, 30.5% and 48.2%, respectively.
      The ART pregnancy rates for Options 1, 2 and 3 were 50%, 60.6% and 80.3%,
      respectively. The mean time to conceive for non-ART pregnancies was 4.2 months.
      The benefit of ART was inversely correlated with the mean EFI score. On
      multivariate analysis, the EFI score was significantly associated with non-ART
      pregnancy (odds ratio 1.629, 95% confidence interval 1.235-2.150). CONCLUSION: In
      daily prospective practice, the EFI was useful for subsequent postoperative
      fertility management in infertile patients with endometriosis.

PMID- 29035800
TI  - Exploring mechanisms of change in schema therapy for chronic depression.
AB  - BACKGROUND AND OBJECTIVES: The underlying mechanisms of symptom change in schema
      therapy (ST) for chronic major depressive disorder (cMDD) have not been studied.
      The aim of this study was to explore the impact of two potentially important
      mechanisms of symptom change, maladaptive schemas (proxied by negative
      idiosyncratic core-beliefs) and the therapeutic alliance. METHODS: We drew data
      from a single-case series of ST for cMDD. Patients with cMDD (N = 20) received on
      average 78 repeated weekly assessments over a course of up to 65 individual
      sessions of ST. Focusing on repeated assessments within-individuals, we used
      mixed regression to test whether change in core-beliefs and therapeutic alliance
      preceded, followed, or occurred concurrently with change in depressive symptoms.
      RESULTS: Changes in core-beliefs did not precede but were concurrently related to
      changes in symptoms. Repeated goal and task agreement ratings (specific aspects
      of alliance) of the same session, completed on separate days, were at least in
      part associated with concurrent changes in symptoms. LIMITATIONS: By design this
      study had a small sample-size and no control group. CONCLUSIONS: Contrary to what
      would be expected based on theory, our findings suggest that change in core
      beliefs does not precede change in symptoms. Instead, change in these variables
      occurs concurrently. Moreover, alliance ratings seem to be at least in part
      colored by changes in current mood state.

PMID- 29035801
TI  - Systematic review with meta-analysis: performance of dried blood spots for
      hepatitis C antibodies detection.
AB  - OBJECTIVES: Dried blood spots (DBS) specimens can be used for hepatitis C virus
      (HCV) infection screening in cases where serum specimens are difficult to obtain.
      However, uncertainties surround the sensitivity and specificity of DBS for HCV
      antibodies (anti-HCV) serology testing. We aimed to evaluate the accuracy of DBS
      use to screen for HCV infection. STUDY DESIGN: We carried out a systematic review
      and meta-analysis. METHODS: Medline and EMBASE databases were searched for
      articles published between 1989 and November 2016. We included studies comparing
      DBS to plasma/serum specimens to detect anti-HCV in adults. Two authors extracted
      data and assessed the quality of the studies using an adapted standards for
      reporting diagnostic accuracy studies (STARD) and independently checked the data
      for accuracy. Meta-analysis was computed with the bivariate and the hierarchical
      summary receiver-operating characteristic models. RESULTS: Twelve studies (3307
      specimens) were analyzed, where 11 of them evaluated the anti-HCV using enzyme
      immunoassays (EIAs), and the remaining one used rapid diagnostic tests. The
      studies were mostly case-controls (83.3%) and from developed countries (66.7%).
      The overall pooled sensitivity (95% confidence interval; CI) and specificity (95%
      CI) of DBS to detect anti-HCV was 98.1% (96.1-99.1%) and 99.7% (98.9-99.9%),
      respectively. In studies using EIAs, the pooled sensitivity and specificity were
      97.3% (94.3-98.8%) and 99.6% (98.5-99.9%), respectively. Considering only studies
      using EIAs, sensitivity analysis excluding one study carried out in people who
      inject drugs showed the pooled sensitivity of 97.8% (96.2-98.8%) and specificity
      of 99.5% (98.5-99.9%). CONCLUSIONS: In testing for anti-HCV by means of EIAs, the
      efficacy of DBS is found to be similar or slightly lower than that of serum
      specimens. However, the risk of finding negative and positive results that are
      both false when using DBS remains present. Therefore, further work including
      optimal storage and processing methodologies are recommended. This is to help
      establish consensus guidelines for use of DBS specimens for anti-HCV screening.

PMID- 29035802
TI  - Magnetic iron oxide/phenylsulfonic acid: A novel, efficient and recoverable
      nanocatalyst for green synthesis of tetrahydrobenzo[b]pyrans under ultrasonic
      conditions.
AB  - A novel magnetic iron oxide supported phenylsulfonic acid (Fe3O4@Ph-SO3H) with
      core-shell structure is prepared, characterized and applied as efficient
      nanocatalyst for green synthesis of tetrahydrobenzo[b]pyrans. The Fe3O4@Ph-SO3H
      was prepared via modification of magnetic iron oxide cores with 1,4
      bis(triethoxysilyl)benzene (BTEB) followed by sulfonation of aromatic rings. The
      Fe3O4@Ph-SO3H was characterized using FTIR, TGA, PXRD, SEM, TEM, VSM and EDX
      techniques. This was effectively applied for synthesis of
      tetrahydrobenzo[b]pyrans in water as green solvent at room temperature under
      ultrasonic conditions. The products were obtained in high to excellent yields at
      short times. The recoverability, reusability and durability of this nanocatalyst
      were studied under applied reaction conditions.

PMID- 29035803
TI  - Untapped conversion of plastic waste char into carbon-metal LDOs for the
      adsorption of Congo red.
AB  - A low-cost novel carbon-metal double layered oxides (C/MnCuAl-LDOs) nano
      adsorbent was synthesized by co-precipitation, for the adsorption of Congo red
      (CR), using modified carbon derived from pyrolysis of polystyrene (PS) plastic
      waste. The synthesized C/MnCuAl-LDOs has a crystalline structure with a high
      surface area of 60.43m2/g and pore size of 99.85A. Adsorption of CR using all
      prepared adsorbents from aqueous solution under equilibrium and kinetic
      conditions were evaluated against different values of the pH (4-10), initial CR
      concentrations (25-250mg/g), contact time (0-310min) and temperature (30-50
      degrees C). The obtained results revealed that C/MnCuAl-LDOs showed maximum
      adsorption capacity for CR among all the used adsorbents. The optimum equilibrium
      time was 180min, whereas acidic medium (pH 4.5) favored the maximum adsorption of
      CR up to 317.2mg/g on C/MnCuAl-LDOs. The adsorption kinetics followed the pseudo
      second-order model, whereas Freundlich adsorption isotherm fitted best to
      obtained data in comparison to Langmuir adsorption isotherm. The results
      suggested that C/MnCuAl-LDOs is an efficient material for the removal of organic
      pollutants from the wastewater.

PMID- 29035805
TI  - Velocity of lateral drying fronts in film formation by drying of colloidal
      dispersions. A 2D simulation.
AB  - Drying of colloids is always heterogeneous and proceeds by progression of drying
      fronts in various directions at various velocities. The fundamental mechanisms at
      the origin of appearance and motion of drying fronts are still not totally
      understood. This article addresses these questions in the case of lateral drying
      fronts by using the new simulation tool based on cellular automata we recently
      developed (Langmuir 2015 and 2017). For the first time, a 2D simulation is
      proposed. Silica dispersions were used as model colloids to test the simulation.
      Film profiles were measured during drying by optical profilometry as well as
      front velocities by image processing. In the cases of non-circular deposits
      (squares and rectangles), drying fronts in the plane of the film (x,y plane, x
      being the longest side in the case of a rectangle) do not move at the same speed
      along sides and diagonals, the velocity order being diagonal >x (longest side) >y
      (shortest side). The velocity contrast (difference between x and y sides)
      increases with the aspect ratio of the rectangle. This behavior is explained and
      accounted for by the 2D simulation presented in this article. Experimental
      results reasonably well validate the simulation.

PMID- 29035804
TI  - Green electrospun and crosslinked poly(vinyl alcohol)/poly(acrylic acid)
      composite membranes for antibacterial effective air filtration.
AB  - Air pollution has become a major environmental concern given the ever increasing
      levels of particulate matter (PM) and the increased in treatment-resistant
      bacterial and viral strains. Major efforts are therefore required into the
      development of air filtration and purification technology as well as novel,
      alternative antiviral and antibacterial treatment modalities. Here, we report an
      environmentally friendly method for the generation of multifunctional poly(vinyl
      alcohol)/poly(acrylic acid) (PVA-PAA) composite membranes via green
      electrospinning and thermal crosslinking. Superhydrophobic silica nanoparticles
      were then incorporated into the fibers resulting in a rough surface, after which
      AgNO3 was introduced, resulting in the formation of Ag nanoparticles through UV
      reduction. The PVA-PAA-SiO2-Ag NPs membranes were found to possess high air
      filtration performance (with >98% filtration efficiency for PM2.5) as well as
      potent antibacterial and antiviral activities. The green synthesis approach
      avoids the use of hazardous organic solvents, thereby bypassing any potential
      toxicity concerns caused by organic solvent residues. These newly designed PVA
      PAA-SiO2 NPs-Ag NPs nanofibrous membranes with many superior features (e.g. high
      filtration efficiency, high tensile strength, biological compatibility, and
      antibacterial properties) can be applied in eco-friendly air filtration
      materials, in particular for personal air filtration devices.

PMID- 29035806
TI  - Reduced graphene oxide/Mn3O4 nanohybrid for high-rate pseduocapacitive
      electrodes.
AB  - Nanostructure Mn3O4 is a promising pseudocapacitive electrode material due to its
      low cost, environmental compatibility, and intrinsically high capacity. However,
      the poor electrical conductivity and low accessible active sites limit its
      performance. We report that one-dimensional (1D) nanoscale Mn3O4 has been coupled
      with reduced graphene oxide (RGO) to fabricate RGO/Mn3O4 nanohybrid (MORGO) as a
      pseudocapacitive electrode material with high capacitance. The selective
      reduction of graphene oxide (GO) in Mn3O4/graphene oxide (MOGO) to reduced
      graphene oxide (RGO) while sustaining the unchanged oxidation state of manganese
      is the key to obtain MORGO. Specific surface area of MORGO is 14 times higher
      than pure Mn3O4, and the charge transfer resistance decreases 3.2 times. These
      enhanced properties lead to excellent specific capacitance of 538 F g-1 at the
      current density of 0.1 A g-1, and of 472 F g-1 at 10 A g-1 in 1 M Na2SO4 aqueous
      electrolyte. The capacitance retained 89% after 2000 cycles, demonstrating its
      excellent long-term cycling stability.

PMID- 29035807
TI  - Exterior foam drainage and flow regime switch in the foams.
AB  - The three-dimensional flow in exterior microscale foams including the Plateau
      borders and nodes are investigated by solving Navier-stoke and continuity
      equations. First, we show the effect of the interfacial mobility and film
      thickness on the dimensionless mean velocity of the exterior foams. The velocity
      of the exterior node-PB is similar to the velocity of single exterior Plateau
      border. Next, we calculated the pressure difference of each element separately
      and obtained their hydraulic resistances. We found out that the hydraulic
      resistance of the exterior Plateau border is always larger than the hydraulic
      resistance of the exterior node, resulting in a consistent channel-dominated
      regime. However, For the interior foams, there is a value of interfacial mobility
      where the node's resistance overcomes the channel's resistance, resulting in a
      switch from the channel-dominated regime to a node-dominated regime. This
      switching point is dependent on the relative length of the channels. Hence, we
      obtained an approximation of the interfacial mobility switching points versus the
      relative length of channels. Moreover, in a form of approximation master curve,
      we showed the dependence of mean velocities of foams and channels' hydraulic
      resistances to a dimensionless combined parameter of Lambda-1 that contains
      interfacial mobility and film thickness together. For both the exterior and
      interior nodes, the velocity and hydraulic resistance are almost constant for
      various Boussinesq numbers since interfacial mobility has a marginal effect on
      node's flow.

PMID- 29035808
TI  - NH2-coordinately immobilized tris(8-quinolinolato)iron onto the silica coated
      magnetite nanoparticle: Fe3O4@SiO2-FeQ3 as a selective Fenton-like catalyst for
      clean oxidation of sulfides.
AB  - A green, robust and eco-friendly procedure for the oxidation of aromatic organic
      sulfides to sulfones using H2O2 catalyzed by NH2-coordinately immobilized tris(8
      quinolinolato)iron onto the silica coated magnetite (Fe3SiO6) has been developed.
      Physicochemical properties of the resulting nanoparticles were investigated by
      means of techniques including X-ray diffraction, scanning electron microscopy,
      thermogravimetric analysis, vibrating sample magnetometer, atomic adsorption
      spectroscopy and FT-IR spectroscopy. The catalytic activity of sulfides oxidation
      showed that this atom-economical protocol provided great yields of various
      sulfones and allowed the sulfide function reaction conducting under the mild
      conditions thus to prevent the sulfide being over-oxidized to sulfoxides. The
      Fe3O4@SiO2-FeQ3 catalysts are magnetically separable and kept stable after
      recycling for 7 consecutive runs without detectable activity loss.

PMID- 29035809
TI  - Synthesis of hollow NiCo2O4 nanospheres with large specific surface area for
      asymmetric supercapacitors.
AB  - Hollow micro-/nanostructured electrode materials with high active surface area
      are highly desirable for achieving outstanding electrochemical properties.
      Herein, we report the successful synthesis of hierarchical hollow NiCo2O4
      nanospheres with high surface area as electrode materials for supercapacitors.
      Electrochemical measurements prove that such electrode materials exhibit
      excellent electrochemical behavior with a specific capacitance reaching 1229 F/g
      at 1 A/g, remarkable rate performance (~83.6% retention from 1 to 25 A/g) and
      good cycling performance (86.3% after 3000 cycles). Furthermore, the asymmetric
      supercapacitor is fabricated with hollow NiCo2O4 nanospheres electrode and
      activated carbon (AC) electrode as the positive and negative, respectively. This
      device exhibits a maximum energy density of 21.5 W h/kg, excellent cycling
      performance and coulombic efficiency. The results show that hollow NiCo2O4
      nanosphere electrode is a promising electrode material for the future application
      in high performance supercapacitors.

PMID- 29035810
TI  - Traditional bullying and cyberbullying: Differences in emotional problems, and
      personality. Are cyberbullies more Machiavellians?
AB  - Few studies have examined differences in emotional problems and personality of
      traditional bullies and cyberbullies. The present study aimed to determine
      whether those engaged in cyberbullying differ in emotional problems, and
      personality from those engage in traditional bullying perpetration. An
      Argentinean sample of 898 high school students was recruited (56% female; mean
      age = 15.2 SD = 1.6). Adolescents completed measures of traditional bullying,
      cyberbullying, self-esteem, anxiety, depression, and personality. A 6% were
      traditional bullies; 8%, cyberbullies; and 4% were involved in both forms; the
      remainders were non involved. Results indicated that cyberbullies showed less
      depression and anxiety than traditional bullies. Also, cyberbullies scored low in
      neuroticism and high in agreeableness compared to traditional bullies. The
      results suggest that cyberbullies are characterized by an emotional and
      personality profile different from traditional bullies. In the discussion we
      analyze the implications of these results.

PMID- 29035811
TI  - Moving towards fast characterization of polymorphic drugs by solid-state NMR
      spectroscopy.
AB  - Solid-state nuclear magnetic resonance (SS-NMR) spectroscopy has become a common
      technique to study polymorphism in pharmaceutical solids at high-resolution.
      However, high-throughput application of high resolution SS-NMR spectroscopy is
      severely limited by the long 1H spin-lattice relaxation (T1) that is common to
      solid phase compounds. Here, we demonstrate the use of paramagnetic relaxation
      reagents such as chromium (III) acetylacetonate (Cr(acac)3) and nickel (II)
      acetylacetonate (Ni(acac)2) for fast data acquisition by significantly reducing
      the T1 value for carbamazepine Forms I, II, III, and dihydrate, cimetidine Forms
      A and B, nabumetone Form I, and acetaminophen Form I polymorphs. High resolution
      13C cross-polarization and magic angle spinning were used to measure T1 values
      for each polymorph. In order to confirm the absence of polymorphic transitions
      during SS-NMR experiments, powder x-ray diffraction was implemented. The amount
      of chromium ions incorporated by the recrystallization process was quantified by
      using inductively coupled plasma optical emission spectroscopy. Our results
      suggest that the paramagnetic ions added to the polymorphs do not affect the
      polymorphic transformation or the quality of NMR spectra. We believe that this
      successful demonstration of fast data collection will enable high-throughput
      utilization of SS-NMR techniques to study polymorphic solids and could set the
      groundwork for NMR crystallography studies.

PMID- 29035812
TI  - Combined GWAS and LDLA approaches to improve genome-wide quantitative trait loci
      detection affecting carcass and meat quality traits in pig.
AB  - Many QTL affecting meat quality and carcass traits have been reported. However,
      in most of the cases these QTL have been detected in non-commercial populations.
      Therefore, a family structured population of 457 F2 pigs issued from an inter
      cross between 2 commercial sire lines was used to detect QTL affecting meat
      quality and carcass traits. All animals were genotyped using the Illumina
      PorcineSNP60 BeadChip platform. Genome-wide association studies were used in
      combination with linkage disequilibrium-linkage analysis to identify QTL. A total
      of 32 QTL were detected. Nine of these QTL exceeded the genome-wide 5%
      significance threshold. We detected 18 QTL affecting carcass composition traits
      and 16 QTL affecting meat quality traits. Using post-QTL bioinformatics analysis
      we highlighted 26 functional candidate genes related to fatness, muscle
      development, meat color and meat pH. Finally, our results shed light on the
      advantage of using different QTL detection methodologies to get a global overview
      of the QTL present in the studied population.

PMID- 29035813
TI  - Energy loss and impact of various stunning devices used for the slaughtering of
      water buffaloes.
AB  - Stock management of the Swiss water buffalo livestock results in the slaughtering
      of about 350 animals per year. As the stunning of water buffaloes still is an
      unresolved issue, we investigated the terminal ballistics of currently used
      perforating stunning devices. Cartridge fired captive bolt devices, handguns and
      a bullet casing gun were tested in a shooting steep by firing on bisected heads,
      forehead plates and soap blocks. Energy loss of captive bolts confirmed their
      inadequacy when used for heavy water buffaloes, notably adult males. As for the
      free projectiles, ballistics revealed that beyond the impact energy, bullet
      deformation has a strong impact on the outcome. Light 9mm Luger or .38 Spl
      bullets as well as large deformable .44 Rem. Magnum bullets should be avoided in
      favor of heavier .357 Magnum deformation ammunition. These data have been
      translated into the development of a new stunning device for water buffaloes
      meeting both animal welfare and occupational safety requirements.

PMID- 29035814
TI  - Enzyme engineering: reaching the maximal catalytic efficiency peak.
AB  - The practical need for highly efficient enzymes presents new challenges in enzyme
      engineering, in particular, the need to improve catalytic turnover (kcat) or
      efficiency (kcat/KM) by several orders of magnitude. However, optimizing
      catalysis demands navigation through complex and rugged fitness landscapes, with
      optimization trajectories often leading to strong diminishing returns and dead
      ends. When no further improvements are observed in library screens or selections,
      it remains unclear whether the maximal catalytic efficiency of the enzyme (the
      catalytic 'fitness peak') has been reached; or perhaps, an alternative
      combination of mutations exists that could yield additional improvements. Here,
      we discuss fundamental aspects of the process of catalytic optimization, and
      offer practical solutions with respect to overcoming optimization plateaus.

PMID- 29035815
TI  - Genipin inhibits allergic responses in ovalbumin-induced asthmatic mice.
AB  - Genipin is a natural compound isolated from the fruit of Gardenia jasminoides
      with various pharmacological effects. In this study, we investigated whether
      genipin effectively alleviates allergic responses in a murine model of ovalbumin
      (OVA)-induced asthma. The mice were administered an intraperitoneal injection of
      OVA on day 0 and 14 to boost the immune response; genipin was then administered
      from day 18 to 23 by oral gavage. On days 21 to 23, mice were OVA-challenged
      using am ultrasonic nebulizer, and airway hyperresponsiveness (AHR) was
      determined on day 24 by plethysmography. Genipin significantly reduced the
      inflammatory cell count in bronchoalveolar lavage fluids (BALF) and AHR, which
      were accompanied by lower interleukin-5 (IL-5), IL-13 and OVA-specific
      immunoglobulin (Ig) E levels in the BALF or serum from OVA-induced asthmatic
      mice. In histology, genipin significantly decreased airway inflammation and mucus
      hypersecretion in OVA-induced asthmatic mice. Additionally, genipin inhibited OVA
      induced increases in the expression of inducible nitric oxide synthase and
      cyclooxygenase-2 proteins. Further, genipin reduced the activity and protein
      levels of matrix metalloproteinase-9 in lung tissue from OVA induced asthmatic
      mice. Overall, genipin effectively alleviated the asthmatic inflammatory response
      in an OVA-induced asthmatic model. Therefore, our results suggest that genipin
      has therapeutic potential for treating asthma.

PMID- 29035816
TI  - Docosahexaenoic acid attenuates carbon tetrachloride-induced hepatic fibrosis in
      rats.
AB  - Fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)
      has been reported to exert beneficial health effects, including hepatoprotection.
      However, the effect of DHA alone has not been well studied, and the mechanism is
      not fully understood. In the present study, we reported the protective effect of
      DHA on carbon tetrachloride (CCl4) induced hepatic fibrosis. Compared with the
      control group, the CCl4 group showed hepatic damage as evidenced by histological
      changes and elevation in serum transaminase activity, fibrosis, inflammation and
      oxidative stress levels. These pathophysiological changes were attenuated by
      chronic DHA supplementation. The anti-fibrotic effect of DHA was accompanied by
      reductions in gene and protein expression of alpha-smooth muscle actin (alpha
      SMA), fibronectin, and collagen in the liver tissue. DHA also attenuated CCl4
      induced elevation of lipid peroxidation (LPO) and decrease of glutathione
      (GSH)/oxidized GSH (GSSG) ratio. The upregulated inflammatory cytokines tumor
      necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-6 by
      CCl4 were also ameliorated by DHA. Peroxisome proliferator-activated receptor
      (PPAR)-gamma upregulation and type I and II receptors for transforming growth
      factor (TGF)-beta (Tbeta-RI and Tbeta-RII) and platelet-derived growth factor
      (PDGF)-beta receptor (PDGF-betaR) downregulation on both mRNA and protein levels
      were observed by DHA treatment compared to CCl4 group. Moreover, in vitro study
      showed that DHA inhibited HSC activation, being associated with elevating
      PPARgamma level and reducing the phosphorylation levels of Smad2/3 and ERKs,
      which are downstream intermediates of TGFbeta and PDGF receptors, respectively.
      Taken together, the hepatoprotective, anti-inflammatory and anti-fibrotic effects
      of DHA appeared to be multifactorial. Further, one of the mechanisms of the anti
      fibrotic effect of chronic DHA supplementation is probably through PPARgamma
      signaling to interrupt TGFbeta/Smad and PDGF/ERK pathways in HSCs.

PMID- 29035817
TI  - Electroformation of double vesicles using an amplitude modulated electric field.
AB  - Double vesicles are a promising model to mimic eukaryotic cells, yet effective
      preparation methods with high yields and stable double vesicles are scarce.
      Previously reported electroformation methods were mainly based on sinusoidal AC
      fields. Using a combination of sinusoidal and amplitude modulated (AM) electric
      fields lipid double vesicles could be produced for the first time by a simple
      electroformation process. First lipid domes formed in a sinusoidal AC field. The
      domes grew into tubes during the subsequent application of an AM field. These
      tubes deformed into double vesicles to minimize their free energy in accordance
      with the area-difference-elasticity model. Two forces are involved to explain the
      mechanism behind tube formation. The pulling force (F) is responsible to drag the
      domes into tubular vesicles, but has to overcome a critical force (Fc). The most
      important parameters of the electrical field were explored systematically. In our
      work, a maximum yield for double vesicles of 63% was achieved. These vesicles
      proved to be stable for one week at least. Hence our method could provide a way
      to fabricate novel cell models.

PMID- 29035818
TI  - Skin-penetrating polymeric nanoparticles incorporated in silk fibroin hydrogel
      for topical delivery of curcumin to improve its therapeutic effect on psoriasis
      mouse model.
AB  - A poor percutaneous penetration capability for most topical anti-inflammatory
      drugs is one of the main causes compromising their therapeutic effects on
      psoriatic skin. Even though curcumin has shown a remarkable efficacy in the
      treatment of psoriasis, its effective penetration through the stratum corneum is
      still a major challenge during transdermal delivery. The aim of our study was to
      design skin-permeating nanoparticles (NPs) to facilitate delivery of curcumin to
      the deeper layers of the skin. A novel amphiphilic polymer, RRR-alpha-tocopheryl
      succinate-grafted-epsilon-polylysine conjugate (VES-g-epsilon-PLL) was
      synthesized and self-assembled into polymeric nanoparticles. The nanoparticles of
      VES-g-epsilon-PLL exhibiting an ultra-small hydrodynamic diameter (24.4nm) and a
      positive Zeta potential (19.6mV) provided a strong skin-penetrating ability in
      vivo. Moreover, curcumin could effectively be encapsulated in the polymeric
      nanoparticles with a drug loading capacity of 3.49% and an encapsulating
      efficiency of 78.45%. In order to prolong the retention time of the ultra-small
      curcumin-loaded nanoparticles (CUR-NPs) in the skin, silk fibroin was used as a
      hydrogel-based matrix to further facilitate topical delivery of the model drug.
      In vitro studies showed that CUR-NPs incorporated in silk fibroin hydrogel (CUR
      NPs-gel) exhibited a slower release profile of curcumin than the plain CUR-gel,
      without compromising the skin penetration ability of CUR-NPs. In vivo studies on
      miquimod-induced psoriatic mice showed that CUR-NPs-gel exhibited a higher
      therapeutic effect than CUR-NPs as the former demonstrated a more powerful skin
      permeating capability and a more effective anti-keratinization process. CUR-NPs
      gel was therefore able to inhibit the expression of inflammatory cytokines (TNF
      alpha, NF-kappaB and IL-6) to a greater extent. In conclusion, the permeable
      nanoparticle-gel system may be a potential carrier for the topical delivery of
      lipophilic anti-psoriatic drugs.

PMID- 29035819
TI  - Preparation of envelope-type lipid nanoparticles containing gold nanorods for
      photothermal cancer therapy.
AB  - The use of gold nanorods (AuNRs) that produce heat in response to near infrared
      (NIR) irradiation is an attractive approach to cancer photothermal therapy. AuNRs
      are usually prepared by using a highly toxic detergent: cetyltrimethylammonium
      bromide (CTAB). Thus, the removal of CTAB from the reaction mixture, and further
      stabilization of the surface of the AuNRs is required. In the present study,
      AuNRs were encapsulated in a multifunctional envelope-type nano device (AuNR
      MEND) formed with an SS-cleavable and pH-activated lipid-like material. In the
      process of encapsulation, AuNRs were first stabilized with bovine serum albumin
      (AuNR-BSA), and then further encapsulated in the lipid envelope by the ethanol
      dilution method. The in vitro photothermal cytotoxicity of AuNR-MEND was further
      demonstrated on 4T1 breast cancer cells. After NIR radiation, the temperature of
      the medium was increased to approximately 60 degrees C, and cell viability was
      drastically decreased to approximately 11%. However, this cytotoxic effect cannot
      simply be explained by medium heating. It therefore appears that intracellular
      delivery of the AuNRs is a key factor for achieving a high degree of
      cytotoxicity. Dose dependent cytotoxicity data revealed that a higher dose of
      AuNR-MEND resulted in the complete destruction of the cells when they were
      subjected to NIR irradiation, while the cell survival rate reached a plateau at
      30% in the case of AuNR-BSA. Apoptosis was induced after treatment with the
      nanoparticles. AuNR-MEND showed superior cellular uptake activity over AuNR-BSA.
      Thus, delivering AuNR by means of functionalized lipid nanoparticles represents a
      promising approach to induce NIR-triggered apoptosis.

PMID- 29035820
TI  - Real-time monitoring of amyloid fibrillation by electrical impedance
      spectroscopy.
AB  - Electrical impedance spectroscopy (EIS) appears a promising label-free
      methodology for the investigation of processes related to the aggregation of
      macromolecules in solution. Here, we explore the EIS technique as a convenient
      tool for studying the irreversible aggregation of human insulin and describing
      its corresponding fibrillation kinetics. The in situ measurement of the
      electrical response of pure insulin solutions at 60 degrees C allows for the real
      time monitoring of the protein fibrillation as a function of the incubation time.
      The fitting of the EIS data through an equivalent circuit based on a constant
      phase element provides a simple set of electric parameters whose abrupt changes
      can be associated to transitions occurring in the organization of the
      macromolecules. For establishing the reliability of the method proposed, we have
      compared the protein aggregation profile collected from the EIS data to that
      obtained from a conventional fluorescence methodology where Thioflavin T (ThT) is
      used as a dye probe. The description of the fibrillation process is quite similar
      in both cases, since characteristic times of the same order were found for the
      consecutive processes associated to the initial lag phase of insulin
      fibrillation, to the rapid growth of amyloidal aggregates and to the final
      saturation step. Our results suggest that in situ EIS can be considered as a
      promising approach for the real-time label-free monitoring of protein fibril
      formation.

PMID- 29035821
TI  - Neuronal nitric oxide synthase is involved in CB/TRPV1 signalling: Focus on
      control of hippocampal hyperexcitability.
AB  - Cannabinoids (CB), transient receptors potential vanilloid type 1 (TRPV1) and
      nitric oxide (NO) were found to be interlinked in regulating some neuronal
      functions such as membrane excitability and synaptic transmission. TRPV1 play a
      fundamental role since it represents a synaptic target for CB that triggers
      several downstream cellular pathways. In this regard, recent evidence report that
      TRPV1 could influence NO production by modulating neuronal NO synthase (nNOS)
      activity. In the present research, we pointed to manipulate nNOS function to
      assess its role on TRPV1 signalling in hyperexcitability conditions elicited in
      the dentate gyrus of hippocampal formation. The activation of TRPV1 receptors is
      achieved by administering capsaicin (CAP), the main TRPV1 agonist exerting a
      widely reported proepileptic effects. In order to focus on nNOS activity, we used
      7-nitroindazole (7NI), nNOS inhibitor, or L-Arginine (ARG), NO precursor, before
      CAP. Then, the effects of each of these co-administration protocols were tested
      in presence of WIN 55,212, a CB agonist. The study was conducted in rats using an
      electrically-induced acute model of temporal lobe hyperexcitability, the Maximal
      Dentate Activation (MDA), considering different indicators of paroxysmal activity
      such as: percentage of responses to electrical stimulation, MDA discharge
      parameters and threshold current intensity for MDA. Data showed that the
      excitatory effects of CAP were reduced by 7NI and enhanced by ARG pretreatments,
      respectively. In addition, the co-treatment with WIN counteracted CAP effect,
      substantially resulting in an inhibitory effect. Finally, the CAP-WIN functional
      interaction appeared to be modulated by interfering with NO signalling since 7NI
      increased the inhibitory effect induced by the co-treatment with CAP and WIN,
      whereas ARG reduced it. These findings suggest that nNOS function could be
      involved in the CB/TRPV1 signalling and shed light on a new putative cannabinoid
      related control of neuronal hyperexcitability in the hippocampus.

PMID- 29035822
TI  - Intraoperative direct cortical stimulation motor evoked potentials: Stimulus
      parameter recommendations based on rheobase and chronaxie.
AB  - OBJECTIVE: To determine optimal interstimulus interval (ISI) and pulse duration
      (D) for direct cortical stimulation (DCS) motor evoked potentials (MEPs) based on
      rheobase and chronaxie derived with two techniques. METHODS: In 20 patients under
      propofol/remifentanil anesthesia, 5-pulse DCS thenar MEP rheobase and chronaxie
      with 2, 3, 4 and 5ms ISI were measured by linear regression of five charge
      thresholds at 0.05, 0.1, 0.2, 0.5 and 1msD, and estimated from two charge
      thresholds at 0.1 and 1msD using simple arithmetic. Optimal parameters were
      defined by minimum threshold energy: the ISI with lowest rheobase2*chronaxie, and
      D at its chronaxie. Near-optimal was defined as threshold energy <25% above
      minimum. RESULTS: The optimal ISI was 3 or 4 (n=7 each), 2 (n=4), or 5ms (n=2),
      but only 4ms was always either optimal or near-optimal. The optimal D was ~0.2
      (n=12), ~0.1 (n=7) or ~0.3ms (n=1). Two-point estimates closely approximated five
      point measurements. CONCLUSIONS: Optimal ISI/D varies, with 4ms/0.2ms being most
      consistently optimal or near-optimal. Two-point estimation is sufficiently
      accurate. SIGNIFICANCE: The results endorse 4ms ISI and 0.2msD for general use.
      Two-point estimation could enable quick individual optimization.

PMID- 29035823
TI  - Ratiometric drug delivery using non-liposomal nanocarriers as an approach to
      increase efficacy and safety of combination chemotherapy.
AB  - The observation that different drug ratios of the same drug combination can lead
      to synergistic or antagonistic effects when tested against the same cancer cell
      line in vitro gave rise to a new trend, the ratiometric delivery. This strategy
      consists of co-encapsulating a specific synergistic ratio of a drug combination
      into a nanocarrier so that synergism observed in vitro will be faithfully
      translated to in vivo, optimizing combination therapy. In this review we focus on
      how to quantify synergism in vitro, followed by how this affected the evolution
      of nanocarriers culminating in the ratiometric delivery, and finally we summarize
      the results of the non-liposomal formulations that were built upon this concept.

PMID- 29035824
TI  - Knockdown of Diaph1 expression inhibits migration and decreases the expression of
      MMP2 and MMP9 in human glioma cells.
AB  - As the most common primary central nervous system tumor, glioma is characterized
      by high levels of mortality and migration. Unclear boundary with normal brain
      tissue results in poor treatment. The mammalian diaphanous-related formin 1
      (Diaph1) which belongs to formin-homology protein family, is a target of RhoA and
      involved in a number of actin-related biological processes, which abnormally
      expressed in pathological conditions in a number of tumors. Immunohistochemical
      analysis showed that Diaph1 was overexpressed in glioma tissues compared with
      normal human brain tissue. Diaph1 gene silencing RNA interference (RNAi)
      significantly inhibited the migratory activity of human glioma cell lines U87 and
      U251. Moreover, data obtained from qRT-PCR and Western-blot analysis showed that
      the mRNA and protein expression of matrix metalloproteinase2 and 9 (MMP2 and
      MMP9) was significantly suppressed in these Diaph1 knockdown cell lines, as well
      as gelatin zymography analysis revealed that the activity of MMP2 and MMP9 in
      conditioned medium was markedly decreased. In conclusion, our data demonstrate
      that Diaph1 is highly expressed in human glioma, plays a significant role in
      glioma cell migration, and can influence the expression and activity of MMP2 and
      MMP9 indirectly in human glioma cell lines U87 and U251. We provide a theoretical
      basis for further experimental studies and Diaph1 using on glioma therapy.

PMID- 29035825
TI  - Effect of a combination of mometasone furoate, levofloxacin, and retinyl
      palmitate with an in situ gel-forming nasal delivery system on nasal mucosa
      damage repair in an experimental rabbit model.
AB  - BACKGROUND: In this study a combination of Mometasone Furoate (MF)+Levofloxacin
      hemihydrate (LH)+Retinyl palmitate (RP) with an in situ gel-forming delivery
      system was evaluated at different stages of nasal mucosal damage repair in a
      rabbit maxillary sinus model. METHODS: In this study, 28 rabbits were included
      and assigned randomly to four groups. In all rabbits, a standard ostium was
      opened in the medial wall of the maxillary sinus by using a drill. Two different
      subsequently prepared gels with an in situ gel-forming delivery system were used.
      Of these 14 nasal cavities, combination 1 (active combination) was applied daily
      to 5, combination 2 (placebo) to 5, while 4 did not receive any pharmaceutical
      treatment. The diameter of the ostium was measured. Histopathological assessment
      was performed. RESULTS: After 2, 3 and 4 weeks, the ostium diameter was
      significantly wider in the group where gel 1 had been applied compared to both
      the placebo group and control group. In the group treated with gel 1, after 2, 3
      and 4 weeks the presence of superficial cilia was significantly greater, surface
      epithelium significantly less. In the 4th week, histologic scores for
      fibroblastic proliferation and vascular proliferation in the group treated with
      gel 1 were better than in either the control group or the placebo group. With gel
      1, chronic inflammation parameters were also significantly lower than in the
      other groups. CONCLUSION: The MF+LH+RP mixture with an in situ gel-forming nasal
      delivery system applied for wound healing after FESS prevents the formation of
      stenosis and is favorable for proper wound healing.

PMID- 29035826
TI  - Effects of gallic acid on hemodynamic parameters and infarct size after ischemia
      reperfusion in isolated rat hearts with alloxan-induced diabetes.
AB  - Diabetic rats are more susceptible to myocardial ischemia-reperfusion injury than
      control rats. The aim of the present study was to evaluate the cardioprotective
      effect of gallic acid (GA) on isolated rat hearts with alloxan-induced diabetes
      mellitus. Adult male Sprague-Dawley rats were divided randomly into three groups:
      control, untreated diabetic and diabetic animals treated with (GA, 25mg/kg).
      Diabetes was induced by 120mg/kg alloxan injection. Eight weeks after GA
      administration, the hearts were isolated and exposed to myocardial ischemia
      reperfusion. The body weight, blood glucose, hypertrophy index, left ventricular
      function, infarct size, cardiac markers and oxidative stress were measured. In
      the diabetic group, body weight, cardiac contractility (+/-dp/dt), glutathione
      peroxidase (GPx) level (p<0.001), left ventricular developed pressure (LVDP),
      rate pressure product (RPP), superoxide dismutase (SOD) and catalase (CAT) levels
      (p<0.01) as well as the heart weight (p<0.05) significantly reduced. However,
      blood glucose, infarct size, hypertrophy index, lactate dehydrogenase (LDH),
      creatine kinase-MB (CK-MB, p<0.001) and troponin-I (cTnI) levels (p<0.05)
      significantly increased in the diabetic rats compared with the control group.
      Nevertheless, administration of GA improved significantly LVDP, +/-dp/dt, infarct
      size, LDH, CK-MB (p<0.001), blood glucose, the heart weight (p<0.01), body
      weight, RPP, hypertrophy index, antioxidant enzyme and cTnI levels (p<0.05) in
      the diabetic rats. The results of this study indicated that in the diabetic rats,
      left ventricular dysfunction and hypertrophy significantly induced possibly by
      oxidative stress. Moreover, GA as a potent antioxidant improved both left
      ventricular dysfunction and hypertrophy.

PMID- 29035827
TI  - Ginsenoside Rg3 enhances the anti-proliferative activity of erlotinib in
      pancreatic cancer cell lines by downregulation of EGFR/PI3K/Akt signaling
      pathway.
AB  - Erlotinib has shown activity in the management of pancreatic cancer. However, the
      benefit of EGFR blockade is limited due to EGFR independent PI3K/Akt signaling
      pathway. Studies have reported that Ginsenoside Rg3 strongly inhibited PI3K-Akt
      signaling pathway of many carcinomas. We aimed to investigate the activity of
      Ginsenoside Rg3 to sensitize erlotinib in treating pancreatic cancer in vitro and
      in vivo. Human pancreatic cancer cell lines BxPC-3 and AsPC-1 were used. Cell
      proliferation and colony formation assay, Annexin V/PI apoptosis analysis,
      Western blot analysis, immunohistochemistry and in vivo study were carried out.
      Ginsenoside Rg3 enhanced the anti-proliferative effects of erlotinib in BxPC-3
      and AsPC-1 pancreatic cancer cells and xenograft. Ginsenoside Rg3 enhanced
      erlotinib-induced apoptosis and increased caspase-3,9 and PARP cleavage
      expression levels. Erlotinib/Ginsenoside Rg3 treatment decreased the levels of p
      EGFR, p-PI3K, and p-Akt expression significantly. Ginsenoside Rg3 could enhance
      the efficacy of erlotinib to inhibit the proliferation of pancreatic cancer cells
      via induction of apoptosis and downregulation of the EGFR/PI3K/AKT pathway.

PMID- 29035828
TI  - The role of CIP2A in cancer: A review and update.
AB  - Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a characterized human
      oncoprotein that is able to promote cancer cells proliferation, anchorage
      independent cell growth and resistance to apoptosis. CIP2A inactivates protein
      phosphatase 2A (PP2A) which down-regulates Akt (Protein Kinase B) phosphorylation
      and stabilizes c-Myc (c-Myc oncogene product) in cancer cells. CIP2A has been
      studied in the most of human malignancies. Here we discuss the role of CIP2A in
      cancer and give a summary of CIP2A expression in malignancies. Also, where
      available we indicated the association of CIP2A with the stage of cancers and
      patients prognosis, explain its localization and the possibility of targeting
      CIP2A in different cancers.

PMID- 29035829
TI  - MiR-129 inhibits cell proliferation and metastasis by targeting ETS1 via
      PI3K/AKT/mTOR pathway in prostate cancer.
AB  - New evidence suggests that microRNAs (miRNAs) play an important role in
      regulating the development and progression of prostate cancer. However, their
      specific functions and mechanisms remained to be further explored. MiR-129 has
      been reported in gastric cancers, colon cancer and lung cancer. In this study, we
      disclosed a new tumor suppresser function of miR-129 in prostate cancer. The
      purpose of our study is to clarify the effects of miR-129 in cellular processes
      correlated with cancer development and progression of prostate cancer cell by
      regulating ETS1. MiR-129 and ETS1 expression in prostate cancer tissues, tumor
      adjacent tissues and cells were tested by quantitative real-time PCR. We
      validated the target relationship between miR-129 and ETS1 by dual luciferase
      reporter gene system. MTT, colony formation, tumorigenesis assays, flow
      cytometry, wound healing and transwell assays were used to analyze cell
      viability, proliferation, migration, and invasiveness in vivo and in vitro. The
      level of ETS1 protein expression was detected by western blot. Here we
      demonstrate that miR-129 have a relatively reduced expression in prostate cancer
      cell lines and tissues. Morever, the miR-129 inhibits the expression of ETS1 by
      binding its 3'-UTR. The overexpression of miR-129 can inhibit PC-3 cell
      viability, proliferation, migration and invasion through targeting ETS1 by
      PI3K/AKT/mTOR signaling pathway. These findings suggested that miR-129 could
      directly suppress ETS1, which might be one of potential mechanisms in inhibiting
      cell processes including viability, proliferation, migration and invasiveness of
      prostate cancercells and it provides new clues for us to understand the
      carcinogenesis of prostate cancer. In addition, it may help to develop a
      treatment approach for ETS1-activated prostate cancer.

PMID- 29035830
TI  - Hypolipemiant and antioxidant effects of Eugenia brasiliensis in an animal model
      of coconut oil-induced hypertriglyceridemia.
AB  - We investigated the effects of chronic administration of crude hydroalcoholic
      extract (CHE) and crude acetone extract (CAE) obtained from leaves of Eugenia
      brasiliensis species on hypertriglyceridemia and oxidative stress caused by the
      chronic administration of coconut oil. Rats received CHE or CAE (50, 100 or
      150mg/kg, orally) for 30days, plus coconut oil (2mL, orally) or saline for 15th.
      Triglyceride levels, liver cell lipid accumulation, thiobarbituric acid reactive
      substances (TBA-RS), total sulfhydryl content and the activities of antioxidant
      enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase
      (GSH-Px) were evaluated in the blood and liver of rats. Results showed that
      chronic administration of CHE or CAE was able to prevent hypertriglyceridemia and
      decrease the lipid droplets in liver cells, as well as the increase in TBA-RS,
      the reduction in total sulfhydryl content and CAT activity in the blood and
      prevent total or partial the increase in CAT and reduction in SOD and GSH-Px
      activities in the liver. These findings indicate that both extracts may have
      hypolipidemic and antioxidant effects.

PMID- 29035831
TI  - The effects of novel chitosan-targeted gemcitabine nanomedicine mediating
      cisplatin on epithelial mesenchymal transition, invasion and metastasis of
      pancreatic cancer cells.
AB  - OBJECTIVE: The study aimed to evaluate the effects involved with the novel
      chitosan gemcitabine (Gem) nanoparticles mediating cisplatin (DDP) on epithelial
      mesenchymal transition (EMT), invasion and metastasis of pancreatic cancer (PC)
      cells. METHODS: A total of 62 healthy purebred BALB/C of specific-pathogen free
      (SPF) female nude mice were recruited and a SW1990 cell line was subsequently
      cultured. A heterotopic xenograft tumor model was constructed. After determining
      the optimal drug concentration, the nude mice were assigned into the control,
      glycol chitosan (GC)-Gem microsphere, antibody Complex (Abc)-GC-Gem and Abc-GC
      Gem microsphere+DDP groups (n=8 in each group). The tumor morphology of the nude
      mice was observed and HE staining was used to observe the pathological changes of
      the respective tissues. TUNEL staining was performed to detect cell apoptosis,
      while immunohistochemistry was employed for analysis of the positive expression
      rate of EGFR and the number of microvessel density (MVD). Both RT-qPCR and
      Western blotting were utilized for mRNA and protein expressions of VEGF, EGFR,
      Bcl-2, Bax, Survivin, Bak, E-cadherin and Vimentin analysis. RESULTS: The optimal
      drug concentration of Gem was determined to be 120mg/m2. In comparison to the
      control group, tumor size, weight, positive expression rate of EGFR and tumor
      MVD, as well as mRNA and protein expressions of Bax and E-cadherin decreased,
      while the inhibition rate (IR) and apoptosis index (AI), expression of VEGF,
      EGFR, Bcl-2, Survivin, Bak and Vimentin increased in the GC-Gem microsphere, Abc
      GC-Gem microsphere and Abc-GC-Gem microsphere+DDP groups. Compared with the GC
      Gem microsphere group, Abc-GC-Gem and Abc-GC-Gem microsphere+DDP groups had
      decreases concerning tumor size and weight, positive rate of protein expression
      of EGFR and tumor MVD, as well as the expression of Bax and E-cadherin, and
      enhances on IR and AI, expression of VEGF, EGFR, Bcl-2, Survivin, Bak, and
      Vimentin, which were the most obvious in the Abc-GC-Gem+DDP group (P<0.05).
      CONCLUSION: Novel Gem nanoparticles aid in mediating DDP to inhibit PC cell
      invasion and migriation, promote PC cell apoptosis and enhance the efficacy of
      chemotherapy. Our findings demonstrated that Gem administered in combination with
      DDP was more effective than Gem alone.

PMID- 29035832
TI  - New insights into Vinca alkaloids resistance mechanism and circumvention in lung
      cancer.
AB  - Nowadays, lung cancer, as a health problem in worldwide, has high mortality both
      in men and women. Despite advances in diagnosis and surgical techniques of lung
      cancer in recent decades, chemotherapy is still a fundamentally and extensively
      useful strategy. Vinca alkaloids are a class of important and widely used drugs
      in the treatment of lung cancer, targeting on the Vinca binding site at the
      exterior of microtubule plus ends. Either intrinsic or acquired resistance to
      chemotherapy of Vinca alkaloids has been a major obstacle to the treatment of
      lung cancer, which arose great interests in studies of understanding and
      overcoming resistance. In this review, we focused on the application and
      resistance mechanisms of the Vinca alkaloids such as vinblastine, vincristine,
      vinorelbine and vinflunine in lung cancer. We reviewed characteristic resistance
      mechanisms in lung cancer including over-expression of ATP-binding cassette (ABC)
      transporters P-glycoprotein and structural, functional or expression alterations
      of beta-tubulin (betaII, betaIII, betaIV) which may devote to the development of
      acquired resistance to the Vinca alkaloids; multidrug-resistance proteins (MRP1,
      MRP2, MRP3) and RLIP76 protein have also been identified that probably play a
      significant role in intrinsic resistance. Lung resistance-related protein (LRP)
      is contributed to lung cancer therapy resistance, but is not deal with the Vinca
      alkaloids resistance in lung cancer. Understanding the principle of the Vinca
      alkaloids in clinical application and mechanisms of drug resistance will support
      individualized lung cancer therapy and improve future therapies.

PMID- 29035833
TI  - Vanillic acid attenuates effects of transient bilateral common carotid occlusion
      and reperfusion in rats.
AB  - Cerebral hypoperfusion induced by transient bilateral common carotid arteries
      occlusion (tBCCAO), is associated with deleterious alterations in several
      physiological parameters of the animals. This study aims to investigate the
      effects of vanillic acid (VA) on memory impairment, locomotion and exploratory
      deficits, as well as histological and hippocampal long-term potentiation (LTP)
      injuries induced by tBCCAO procedure followed by reperfusion (BCCAO/R) in rats.
      Adult male Wistar rats (250-300g) were divided randomly into four groups: Sham
      Operated group "Sham"; Vehicle+BCCAO/R group "BCCAO/R"; Vehicle+ Vanillic acid
      group "VA"; VA (100mg/kg) +BCCAO/R group "VA +BCCAO/R". Cerebral hypoperfusion
      was induced after 14days of pretreatment with VA and/or normal saline. To induce
      the animal model of hypoperfusion, bilateral common carotid arteries were
      occluded for 30min, followed by 72h of reperfusion. Subsequently, behavioral,
      histopathological and electrophysiological parameters were evaluated after
      BCCAO/R. Data showed that pretreatment of VA markedly improved locomotion in
      tBCCAO rats compared with the untreated BCCAO/R rats (p<0.05). Moreover,
      pretreatment of VA significantly ameliorated memory impairment in "VA+BCCAO/R"
      group compared with the "BCCAO/R" group (P<0.01). The field excitatory
      postsynaptic potential (fEPSP) amplitude and slope were significantly decreased
      in "BCCAO/R" group compared with Sham group (P<0.001). Data indicate that fEPSP
      amplitude and slope were increased in "VA+BCCAO/R" group compared with the
      "BCCAO/R" group (P<0.001). Furthermore, histopathological observation in VA
      pretreated tBCCAO rats showing markedly attenuated of cell death (P<0.01) and
      arrangement of CA1 neurons as compared with the untreated BCCAO/R rats. Our data
      confirm the protective role of VA against transient cerebral ischemia and
      reperfusion in rats. Moreover, it proposes that VA has a beneficial role in
      cerebrovascular insufficiency states.

PMID- 29035834
TI  - Synergistic effect of mild hypothermia and the Notch inhibitor DAPT against post
      stroke seizures.
AB  - Seizure is a serious complication of stroke, indicating poor prognosis. Notch
      signaling is associated with neuronal activity. Inhibition of Notch signaling
      suppresses seizure activity induced by kainic acid. The present study
      investigated the effect of the Notch inhibitor, DAPT, alone or in combination
      with mild hypothermia, on post-stroke seizures. A global cerebral ischemia (GCI)
      model was performed in Sprague Dawley (SD) male rats. Seizure activity was
      evaluated by the frequency of seizure attacks, seizure severity scores, and
      seizure discharges. Without any intervention, seizures occurred intensively
      between 24h and 48h following GCI. Seizure activity was confirmed using EEG
      monitoring. The expression of Notch intracellular domains (NICD) 1 and 2 were up
      regulated in the cerebral cortex and hippocampus following GCI. DAPT was injected
      into the hippocampus of the rats to inhibit local Notch signaling. Active whole
      body cooling was performed to maintain the core temperatures of rats at 33.5
      degrees C (mild hypothermia). Mild hypothermia and DAPT synergistically inhibited
      NICD 1 and 2 up-regulation, and post-stroke seizures. GCI augmented excitatory
      synaptic neurotransmission by up-regulating glutamate receptor subunits (GluN2A,
      GluA1) and the cotransporter, NKCC1, but attenuated inhibitory synaptic
      neurotransmission by down-regulating gamma amino acid, butyric acid (GABA), and
      the cotransporter, KCC2. DAPT treatment normalized the homeostasis of excitatory
      and inhibitory synaptic neurotransmission, suggesting that aberrant activation of
      Notch signaling is involved in post-stroke seizures. The present study adds to
      the further understanding of the pathogenesis of post-stroke seizures and the
      improvement of the treatment provided with hypothermia.

PMID- 29035835
TI  - Nerve Growth Factor-Beta, purified from bull seminal plasma, enhances corpus
      luteum formation and conceptus development in Bos taurus cows.
AB  - The objective of the current study was to determine if Nerve Growth Factor-Beta
      (NGF), purified from bovine seminal plasma, would improve corpus luteum function
      and enhance conceptus development when administered to cows at artificial
      insemination. Angus cows (n = 60) were synchronized using a GnRH-prostaglandin
      and intravaginal progesterone protocol (7-day CO-Synch/CIDR) and randomly
      allocated to 1 of 2 treatment groups: (1) CONT- 12 mL PBS; or (2) NGF- 296 MUg
      purified NGF in 12 mL PBS administered intramuscularly at insemination (day 0).
      Blood collections were performed to measure plasma concentrations of progesterone
      (days 0, 3, 7, 10, 14, 19) and pregnancy-specific protein B (day 24) using
      immunoassays. Expression of interferon-stimulated genes (ISG15, MX1, MX2, RTP4)
      were assessed in peripheral blood leukocytes on day 19. Transrectal ultrasound
      was performed for measuring corpus luteum size (days 0, 3, 7, 10, 14, 19) and
      pregnancy diagnosis (days 28, 45, 66). Statistical analysis was performed using
      analysis of variance with repeated measures (SAS 9.4, Cary NC). Corpus luteum
      volume and diameter increased over time (p < 0.001), but did not differ between
      treatment groups (p = 0.46). Cows treated with NGF had increased plasma
      progesterone over CONT cows from days 10-19 (p = 0.04). Pregnancy rates at day 28
      were 75% in NGF cows versus 59% in CONT cows (p = 0.13). In pregnant cows,
      pregnancy-specific protein B concentrations at day 24 were greater in NGF than
      CONT cows (p < 0.05). Additionally, fold-change expression of ISG15 and MX2 at
      day 19 were greater in pregnant NGF cows than in pregnant CONT cows (p < 0.05),
      but no differences for MX1 and RTP4 were present. Here we demonstrate that NGF
      administration to cows at insemination improved corpus luteum function, which
      translated to improved early conceptus development as determined by upregulation
      of interferon-stimulated genes and increased pregnancy-specific protein B
      concentrations. These results suggest that seminal plasma NGF could play a role
      in conceptus development and may be important to improve fertility in cattle.

PMID- 29035836
TI  - Effect of initial GnRH and time of insemination on reproductive performance in
      cyclic and acyclic beef heifers subjected to a 5-d Co-synch plus progesterone
      protocol.
AB  - This study evaluated the effect of initial GnRH and timing of AI in a 5-d Co
      synch plus CIDR (device containing 1.38 g of progesterone) protocol on pregnancy
      per AI (P/AI) and pregnancy loss in beef heifers. A secondary objective was to
      determine if the effect of initial GnRH on reproductive performance was
      influenced by cyclicity. Crossbred beef heifers (n = 1068; 301-514 kg of body
      weight, and 13-15 mo of age) at three locations were assigned to either a 5-d Co
      synch plus CIDR protocol with (CIDR5G) or without (CIDR5NG) an initial injection
      of 100 MUg of GnRH at CIDR insertion (Day 0). All heifers received a single dose
      of 500 MUg of cloprostenol at CIDR removal (Day 5) and were divided into two
      groups to receive GnRH and TAI at either 66 or 72 h (Day 8) after CIDR removal.
      All heifers were inseminated by one technician with frozen-thawed semen from 1 of
      4 sires available commercially. Transrectal ultrasonography was performed on Day
      0 to determine cyclicity (presence of CL) and normalcy of the reproductive track,
      and 27 d after TAI to determine pregnancy status. Non-pregnant heifers (n = 470)
      were assigned to either a CIDR5G or a CIDR5NG protocol with TAI at 72 h after
      CIDR removal. Twelve days after second AI, heifers were exposure to bulls for 20
      d and pregnancy diagnoses were performed approximately 30 d after second TAI and
      60 d after bulls were removed to diagnose bull pregnancies and determine
      pregnancy loss rate. The percentage of acyclic heifers was 20.3%. Overall P/AI
      after first TAI was 55.6% (594/1068) and did not differ between CIDR5G and
      CIDR5NG (56.1 vs. 55.1%), or between TAI66 and TAI72 (55.8 vs. 55.4%). However,
      cyclic heifers were more likely to become pregnant than acyclic ones (59.3 vs.
      41.2%; P < 0.01). Moreover, acyclic heifers subjected to the CIDR5NG had fewer
      P/AI than those subjected to CIDR5G (P < 0.01). Overall P/AI after
      resynchronization was 55.1% and did not differ between CIDR5G and CIDR5NG (51.3
      vs. 59.0%). Overall pregnancy loss after first and second TAI were 3.0% (18/594)
      and 3.9% (8/205), respectively. When pregnancy loss data were combined,
      synchronization protocol (4.1 vs. 2.3% for CIDR5NG and CIDR5G; P = 0.01),
      cyclicity (5.8 vs. 2.9% for acyclic and cyclic; P = 0.03) and the interaction
      between synchronization protocol and cyclicity (P = 0.04) were significant. The
      overall cumulative pregnancy at the end of the breeding season was 94.2%
      (1006/1068); acyclic heifers were less likely to be pregnant at the end of the
      breeding season (88.4 vs. 95.8%; P < 0.01). In summary, the initial GnRH
      administration in a 5-d Co-synch plus CIDR protocol that includes a single PGF
      treatment is necessary in acyclic beef heifers to optimize P/AI, but not in
      cyclic heifers. Moreover, omission of initial GnRH was associated to greater
      pregnancy losses, particularly in acyclic heifers. Timing of AI did not affect
      P/AI.

PMID- 29035837
TI  - Testicular cytology by fine needle aspiration in domestic cats.
AB  - In cases where semen collection in tom-cats is not possible, FNA of testes is the
      alternative to evaluate sperm production. Although this technique for the
      diagnosis of fertility problems has been well discussed in other mammals (men,
      dogs, stallions), data for domestic cats are limited. Therefore, the aim of this
      study was to verify the reliability of FNA using needles of small diameters (22G
      and 29G) in testes of domestic cats of different ages to assess the
      spermatogenesis status and to present description of germ cells and Sertoli cells
      for cytological examinations. Thirty-four mixed breed cats aged between four
      months and two years presented for neutering to a Veterinary Hospital were used
      in this study. Under general anesthesia, testicular measures and FNA were
      followed by orchiectomy and imprints of the parenchyma of testes and
      epididymides. Cats were assigned into 3 groups: (G1) 10 cats aged less than 6
      months, (G2) 14 cats aged between 6 months and one year and (G3) 10 cats aged
      more than one year. Cats weighted between 1.5 and 6.0 kg. The mean testicular
      volume (TV cm3) was 0.55 (G1), 1.18 (G2) and 2.66 (G3). Hemorrhages in the needle
      path were observed in more than 70% of testes. Few samples (4/68) were excluded
      due to blood contamination. All germ cells and Sertoli cells were identified and
      quantified in imprint and FNA smears. Incomplete spermatogenesis was observed in
      cats aged less than 6 months using both techniques (FNA and imprint); therefore,
      testicular FNA should not be recommended for cats at this age. Complete
      spermatogenesis was found in 64% of cats aged from 6 months up to one year and in
      all cats aged more than one year. There were no differences of Sertoli cell Index
      (SEI) and Spermatic Index (SI) between FNA and imprints of cats older than 6
      months. In conclusion, FNA using needles of small diameter in the testes of
      domestic cats is viable, reliable and can be used as a tool for the analysis of
      the spermatogenesis status of cats older than 6 months, mainly in cases in which
      semen collection is not possible.

PMID- 29035838
TI  - Effect of two treatment protocols for ketosis on the resolution, postpartum
      health, milk yield, and reproductive outcomes of dairy cows.
AB  - We determined the effect of ketosis treatment with propylene glycol (PG) or PG
      plus l-carnitine and methionine (Metabolase(r), Fatro, Bologna, Italy) on the
      resolution, postpartum health, milk yield, and reproductive performances of dairy
      cows. Blood from 475 Holstein cows was collected weekly until 4 weeks after
      calving to measure blood beta-hydroxybutyrate (BHBA) concentrations. Cows with
      blood BHBA concentration >=1.2 mmol/L were diagnosed with ketosis and were
      enrolled. One hundred and fifty cows diagnosed with ketosis were randomly
      assigned to three treatment groups (Day 0): (1) PG (300 g, PO) for 3 days (PG
      group, n = 50), (2) PG (300 g, PO) plus l-carnitine (1.25 g) plus methionine (5
      g, IV) for 3 days (PG + CM group, n = 50), and (3) no treatment (control group, n
      = 50). On Day 3, blood was collected to evaluate whether the ketosis had
      resolved. Cows in the PG and PG + CM groups with blood BHBA >=1.2 mmol/L were
      retreated for an additional 2 days, and then blood BHBA concentration was
      evaluated on Days 5 and 10. Blood glucose and haptoglobin concentrations, rumen
      fill score (RFS), and body condition score (BCS) were measured on Days 0, 3, 5,
      and 10. Postpartum complications, milk yield during the first 2 months, and
      reproductive outcomes were evaluated. The probability of resolution from ketosis
      was higher (P < 0.05) in the PG + CM group than in the control group on Days 3,
      5, and 10 (odds ratio: 2.6-6.3). Blood BHBA in the PG + CM group was lower (P <
      0.05) than that of the control group on Days 3 and 5, whereas blood glucose in
      the PG + CM group was higher (P < 0.05) than that of the control group on Days 3
      and 5. RFS in the PG and PG + CM groups was higher than that of the control group
      on Day 10 (P < 0.01), while BCS loss from Day 0-10 in the control group was
      higher than those of the PG and PG + CM groups (P < 0.05). Milk yields on the
      30th and 60th days postpartum were higher in the PG + CM group than the control
      and PG groups (P < 0.05). Postpartum complications and intervals between calving
      and first postpartum insemination or pregnancy did not differ among the groups (P
      > 0.05). In conclusion, treatment of dairy cows with PG plus l-carnitine and
      methionine improved the chances of resolution of ketosis and increased milk
      yield, while affecting neither the incidence of postpartum complications nor
      reproductive performance.

PMID- 29035840
TI  - Characteristics of Mexican children and adolescents who died by suicide: A study
      of psychological autopsies.
AB  - OBJECTIVE: In recent years, suicide in children and adolescents has increased
      considerably, becoming the second cause of death in this age group. Therefore,
      the aim of this study was to identify characteristics and factors that could
      precipitate deaths by suicide in children and adolescents. METHODS: Using the
      psychological autopsy method, we studied 28 suicide cases of children and
      adolescents between 10 and 17 years old. Socio-demographic factors,
      characteristics of the suicide and family history were documented. RESULTS: The
      proportion of deaths by suicide was the same in females and males (50% each).
      Most of the suicides were performed at the child/adolescent's home (78.6%) and no
      history of previous suicide attempts were registered (85.7%). Also, the majority
      of suicidal individuals came from a dysfunctional family (60.7%). CONCLUSIONS:
      Our results identified characteristics of children and adolescents that had died
      by suicide, such as dying at their homes and coming from dysfunctional families.
      Knowing the characteristics of children and adolescents that had ended their
      lives by suicide should be considered in future studies to help developing
      preventive programs and strategies for treating suicidal behaviors in Mexican
      children and adolescents.

PMID- 29035841
TI  - Verification of an improved hip joint center prediction method.
AB  - In motion analysis, the hip joint center (HJC) is used to define the proximal
      location of the thigh segment and is also the point about which hip moments are
      calculated. The HJC cannot be palpated; its location must be calculated.
      Functional methods have been proposed but are difficult to perform by some
      clinical populations. Therefore, regression methods are utilized, but yield large
      errors in estimating the HJC location. These prediction methods typically utilize
      the anterior and posterior superior iliac spines, where excessive adipose tissue
      makes correctly locating difficult. A new regression method (Hara) utilizes leg
      length and has been shown to improve HJC location in cadavers and less error than
      previous pelvic based regression methods, such as those proposed by Harrington et
      al. This study compared the accuracy of the HJC location calculated with both of
      the Harrington methods and the Hara method. The coronal knee angle was calculated
      for each method using a static motion analysis trial, and compared to the
      tibiofemoral angle measured on a gold standard digital full-leg coronal
      radiograph. This study demonstrated that the Hara method was more accurate than
      either of the Harrington methods. The mean error between the gold standard x-ray
      measurement and the motion analysis calculation for the Harrington (stepwise and
      LOOCV), the Harrington (linear regression), and Hara regression methods,
      respectively were 6.0 degrees , 4.0 degrees , and 1.8 degrees . Accurately
      modeling the HJC is critical for data interpretation and patient care. This study
      confirmed that the Hara HJC regression method is valid in an in-vivo setting.

PMID- 29035842
TI  - Derivation and characterization of integration-free iPSC line ISRM-UM51 derived
      from SIX2-positive renal cells isolated from urine of an African male expressing
      the CYP2D6 *4/*17 variant which confers intermediate drug metabolizing activity.
AB  - SIX2-positive renal cells isolated from urine from a 51year old male of African
      origin bearing the CYP2D6 *4/*17 variant were reprogrammed by nucleofection of a
      combination of two episomal-based plasmids omitting pathway (TGFbeta, MEK and
      GSK3beta) inhibition. The induced pluripotent stem cells (iPSCs) were
      characterized by immunocytochemistry, embryoid body formation, DNA-fingerprinting
      and karyotype analysis. Comparative transcriptome analyses with human embryonic
      stem cell lines H1 and H9 revealed a Pearson correlation of 0.9243 and 0.9619
      respectively.

PMID- 29035839
TI  - Insights into protein misfolding and aggregation enabled by solid-state NMR
      spectroscopy.
AB  - The aggregation of proteins and peptides into a variety of insoluble, and often
      non-native, aggregated states plays a central role in many devastating diseases.
      Analogous processes undermine the efficacy of polypeptide-based biological
      pharmaceuticals, but are also being leveraged in the design of biologically
      inspired self-assembling materials. This Trends article surveys the essential
      contributions made by recent solid-state NMR (ssNMR) studies to our understanding
      of the structural features of polypeptide aggregates, and how such findings are
      informing our thinking about the molecular mechanisms of misfolding and
      aggregation. A central focus is on disease-related amyloid fibrils and oligomers
      involved in neurodegenerative diseases such as Alzheimer's, Parkinson's and
      Huntington's disease. SSNMR-enabled structural and dynamics-based findings are
      surveyed, along with a number of resulting emerging themes that appear common to
      different amyloidogenic proteins, such as their compact alternating short-beta
      strand/beta-arc amyloid core architecture. Concepts, methods, future prospects
      and challenges are discussed.

PMID- 29035843
TI  - Generation of a human control PBMC derived iPS cell line TUSMi001-A from a
      healthy male donor of Han Chinese genetic background.
AB  - A 59-year old healthy man of Han Chinese genetic background donated his
      peripheral blood mononuclear cells (PBMC). The non-integrating episomal vector
      system was used to reprogram his PBMCs with the human OSKM (Oct4, Sox2, Kl4 and c
      Myc) transcription factors. The pluripotency of transgene-free iPSCs was
      confirmed by immunocytochemistry for pluripotency markers and by the ability of
      the iPSCs to differentiate spontaneously into 3 germ layers in vitro. In
      addition, the iPSC line displayed a normal karyotype. In the studies of disease
      mechanism, the iPSC line can be used as a control.

PMID- 29035844
TI  - Comparison of Radial Access, Guided Femoral Access, and Non-Guided Femoral Access
      Among Women Undergoing Percutaneous Coronary Intervention.
AB  - OBJECTIVES: This study was conducted to determine the association between radial
      access, guided femoral access, and non-guided femoral access on postprocedural
      bleeding and vascular complications after percutaneous coronary intervention
      (PCI). BACKGROUND: Bleeding events and major vascular complications after PCI are
      associated with increased morbidity, mortality, and cost. While the radial
      approach has been shown to be superior to the femoral approach in reducing
      bleeding and vascular complications, whether the use of micropuncture,
      fluoroscopy, or ultrasound mitigates these differences is unknown. METHODS: We
      conducted a post hoc analysis of women in the SAFE-PCI for Women trial who
      underwent PCI and had the access method identified (n = 643). The primary
      endpoint of postprocedure bleeding or vascular complications occurring within 72
      hours or at discharge was adjudicated by an independent clinical events committee
      and was compared based on three categories of access technique: radial, guided
      femoral (fluoroscopy, micropuncture, ultrasound), or non-guided femoral (none of
      the aforementioned). Differences between the groups were determined using
      multivariate logistic regression using radial access as the reference. RESULTS:
      Of the PCI population, 330 underwent radial access, 228 underwent guided femoral
      access, and 85 underwent non-guided femoral access. There was a statistically
      significant lower incidence of the primary endpoint with radial access vs non
      guided femoral access; however, there was no significant difference between
      radial approach and femoral access guided by fluoroscopy, micropuncture, or
      ultrasound. CONCLUSIONS: This post hoc analysis demonstrates that while radial
      access is safer than non-guided femoral access, guided femoral access appears to
      be associated with similar bleeding events or vascular complications as radial
      access.

PMID- 29035845
TI  - Radiation Reduction in the Pediatric Catheterization Laboratory Using a Novel
      Imaging System.
AB  - OBJECTIVES: Radiation dose was compared between two modern imaging systems with
      different x-ray tube technology (Megalix vs Gigalix) and detector type (amorphous
      vs crystalline silicon) at the same institution. BACKGROUND: Further reduction in
      radiation dose than currently reported may be achievable with advances in x-ray
      tube and detector technology. METHODS: Radiation dose (air kerma, dose-area
      product [DAP]) was retrospectively compared for post-transplant pediatric
      patients undergoing right heart catheterization/biopsy (fluoroscopy only) or
      "annual" catheterization with coronary angiography in one of two imaging systems
      between January 2014 and December 2016. Comparisons were also made with published
      radiation doses. RESULTS: A total of 122 right heart catheterizations with biopsy
      were performed in the Megalix/amorphous silicon (Si) lab and 168 in the
      Gigalix/crystalline Si lab. Age and weight were not statistically different for
      the two groups. There was a 50% decrease in median air kerma (2.2 mGy vs 1.1 mGy;
      P<.001) and 66% decrease in median DAP (52.2 MUGy*m2 vs 18.0 MUGy*m2; P<.001) for
      the Gigalix/crystalline Si lab. A total of 24 "annual" catheterizations were
      performed in the Megalix/amorphous Si lab and 22 were performed in the
      Gigalix/crystalline Si lab. There was a 57% reduction in median air kerma (458.6
      mGy vs 198.6 mGy; P<.001) and a 46% reduction in median DAP (2548.0 MUGy*m2 vs
      1367.1 MUGy*m2; P<.01) for the Gigalix/crystalline Si lab. Similar reductions
      were found on comparison with published doses. CONCLUSION: The Gigalix tube and
      crystalline Si detector decrease radiation dose by 50%-60% for fluoroscopy and
      cine acquisition in pediatric patients.

PMID- 29035846
TI  - Current Perspectives and Practices on Chronic Total Occlusion Percutaneous
      Coronary Interventions.
AB  - OBJECTIVES: We sought to examine contemporary perspectives and practices on
      chronic total occlusion (CTO) percutaneous coronary intervention (PCI).
      BACKGROUND: The frequency and success of CTO-PCI have been increasing in recent
      years. METHODS: An online questionnaire was created and distributed to
      cardiologists within the United States and internationally. RESULTS: A total of
      1149 responses were obtained. The United States (n = 845; 73.5%), Asia (n = 98;
      8.5%), Europe (n = 88; 7.7%), South America (n = 42; 3.7%), and Canada (n = 33;
      2.9%) accounted for most responses. Mean practice duration of the respondents was
      16.4 +/- 11.5 years and 66.9% were interventional cardiologists. Most respondents
      agreed that CTO-PCI results in an improvement of patient symptoms (90.7%), left
      ventricular function (79.3%), arrhythmia risk (69.2%), and overall survival
      (63.1%). Interventional cardiologists had a more favorable view of the benefits
      of CTO-PCI as compared with non-interventional cardiologists (P<.001). Most
      respondents estimated the procedural success rates of contemporary CTO-PCI to be
      between 51%-75% (34.2%) and 76%-85% (30.2%), with interventional cardiologists
      estimating higher success rates than non-interventionalists (P<.001).
      Perforation, mortality, and tamponade were the three most concerning
      complications. Time and procedure complexity were reported to be the most
      significant barriers to the development of a CTO-PCI program. CONCLUSIONS: Most
      cardiologists believe that CTO-PCI can provide significant clinical benefits and
      can be accomplished with moderate to high success rates. Interventional
      cardiologists have a more favorable view of CTO-PCI as compared with non-invasive
      cardiologists.

PMID- 29035847
TI  - Prevalence and molecular characterization of bovine Cryptosporidium from dairy
      cows in Northern Thailand.
AB  - Cryptosporidiosis is a common protozoan infection in humans and domestic animals.
      It is the culprit for significant neonatal morbidity in cattle as well as weight
      loss and delayed growth, which leads to large economic losses in the farming
      industry. Furthermore, bovine Cryptosporidium is also a principal source of human
      Cryptosporidium infections. The purpose of this study is to determine prevalence
      and genotype of Cryptosporidium spp. from feces of dairy cows from the northern
      parts of Thailand (Chiang Rai, Chiang Mai, and Lumpang provinces). A total of 500
      fecal samples were collected directly from the rectum and they were examined for
      potential presence of Cryptosporidium infection by using tests such as DMSO
      modified acid fast stain, immunofluorescence antibody test (IFAT) and polymerase
      chain reaction (PCR). The prevalence of Cryptosporidium spp. was 5% by DMSO
      modified acid fast stain, 7% by IFAT and 7.6% by PCR respectively. The main
      genotypes of Cryptosporidium spp. identified were Cryptosporidium parvum and
      Cryptosporidium bovis. Therefore, as a result of this study, it can be said that,
      due to the potential cross-species transmission of Cryptosporidium parvum,
      infected dairy cows may pose a potential zoonotic risk to humans.

PMID- 29035848
TI  - Animal level risk factors associated with Babesia and Theileria infections in
      cattle in Egypt.
AB  - In present study, blood samples were collected randomly from 439 cows at three
      main regions of Egypt (northern, central and southern). Molecular diagnosis of
      Babesia and Theileria infections by PCR amplification of DNA (gene) fragments,
      then cloning and sequencing of the positive samples were conducted. A
      questionnaire was created to imply the assumed risk factors and logistic
      regression statistical analysis was carried out to appraise the potential factors
      on the animal level. The results revealed that 49 (11.16%) and 45 (10.25%) cattle
      were infected with Babesia and Theileria parasites, respectively. B. bigemina
      (7.97%) and T. annulata (9.56%) were the most prevalent parasites. For Babesia
      sp., final multivariate logistic regression analysis showed a significant
      association between the infection and irregular use of antiprotozoal drugs (P =
      0.003; OR: 0.28; 95% CI: 0.12-0.65), management practice (P = 0.029; OR: 6.66;
      95% CI: 1.21-36.59) and ecology area (P = 0.006; OR: 5.62; 95% CI: 1.63-19.31).
      However, for Theileria sp. infection, animal breed (P = 0.003; OR: 0.44; 95% CI:
      .45-1.00) and irregular use of antiprotozoal drugs (P<0.001; OR: 4.22; 95% CI:
      2.62-5.60) were the potential risk factors. The results of the present study
      declare the prevalent bovine Babesia and Theileria sp. in Egypt based on
      molecular description. An impression on the potential risk factors associated
      with infections was obtained. Recognition of the potential risk factors
      associated with tick borne disease may be helpful to construct the best
      preventive measures.

PMID- 29035849
TI  - A new species of Spauligodon (Nematoda; Oxyuroidea; Pharyngodonidae) and other
      Nematodes in Cyrtodactylus epiroticus (Squamata; Gekkonidae) from Papua New
      Guinea.
AB  - Spauligodon papuensis sp. nov. from the large intestines of Cyrtodactylus
      epiroticus (Gekkonidae) from Papua New Guinea is described and illustrated.
      Spauligodon papuensis sp. nov. represents the 54th species assigned to the genus
      and the second species from the Oceanic Region. The new species is separated from
      congeners by the unique combination of aspinose filamentous tail and no spicule
      in the male; and spinose filamentous tail, fusiform, flanged eggs, and postbulbar
      vulva in the female. Four additional species of nematodes were also found in C.
      epiroticus: mature specimens of Cosmocerca zugi, Falcaustra papuensis,
      Physalopteroides milnensis and larvae of Abbreviata sp.

PMID- 29035850
TI  - Anti-angiogenic and anti-lymphangiogenic role of praziquantel and artemether in
      experimental mansoniasis.
AB  - Angiogenesis is one of the pillars of neoplasia. Lymphangiogenesis in context of
      granulomas is not yet understood. This study aimed to evaluate the role of
      praziquantel (PZQ) and artemether (ART) as anti-angiogenic and anti
      lymphangiogenic drugs in Schistosoma mansoni induced experimental hepatic model
      through immunohistochemical and serological studies, this can be used as a
      potential novel prophylactic approach in hepatic malignancy prevention and
      possible management. Forty female CD-1 Swiss albino mice were used divided into 4
      groups (10 mice each); control healthy, control infected untreated, PZQ-treated
      and ART-treated. Angiogenic and lymphangiogenic effect of the drugs assessed
      pathologically through counting of the newly formed capillaries and lymphatics
      that immunohistochemically expressed by vascular Endothelial Growth Factor
      (VEGF), CD34 and D2-40 in liver sections using Cell Image Analyzer and
      serologically by evaluation of serum level of Tumor Necrosis Factor-Alpha (TNF
      alpha). Our results showed significant decrease in serum TNF-alpha in ART-treated
      group compared to control infected and PZQ treated groups. ART exhibited
      significant anti-angiogenic role on granulomas illustrated by remarkable milder
      intensity and significantly lower expression values of VEGF and CD34
      immunostaining compared to PZQ and non-treated groups. Also, ART treated group
      exhibited negative D2-40 expression in the granulomas in contrast to the other
      groups, supporting the potent ART' anti-lymphangiogenic role that exceeded PZQ.
      In conclusion, ART showed not only anti-angiogenic effect but also prominent anti
      lymphangiogenic effect on hepatic S. mansoni granulomas compared to PZQ. Our
      study supports the potential use of ART as a potential novel prophylactic
      approach in hepatic malignancy prevention and possible management.

PMID- 29035851
TI  - Mitochondrial genotyping of Fascioloides magna from Bavaria, Germany.
AB  - In last few years, a great effort has been made to understand genetic
      interrelationships of European and North American populations of giant liver
      fluke Fascioloides magna (Trematoda, Fasciolidae). In Europe, spatial
      distribution of this parasite is evidently dynamic and ongoing process since new
      F. magna populations have constantly been emerging. Most recently, occurrence of
      F. magna in red deer (Cervus elaphus), sika deer (Cervus nippon), fallow deer
      (Dama dama), roe deer (Capreolus capreolus), and wild boar (Sus scrofa) was
      reported from north-eastern Bavaria in Germany. Fascioloides magna specimens
      collected from those hosts were genotyped using two mitochondrial regions;
      cytochrome c oxidase (cox1) and nicotinamide dehydrogenase (nad1). Results were
      compared with reference mitochondrial haplotypes of previously characterized
      European F. magna populations from northern Italy, Czech Republic/Poland, and the
      Danube floodplain forests. The study revealed genetic uniformity of F. magna
      specimens from Germany with flukes from the Czech focus, what indicated that
      fascioloidosis has been spreading beyond well established Czech focus into
      neighbouring countries.

PMID- 29035852
TI  - Abundance and species composition of Culicoides spp. biting midges near cattle
      and horse in South-Eastern Poland.
AB  - The aim of the study was to estimate and compare the distribution of Culicoides
      biting midges species at farms with different main hosts - cattle and horse.
      Culicoides spp. are known vectors of arboviruses including African horse sickness
      virus (AHSV), bluetongue virus (BTV) and Schmallenberg virus (SBV). The latter
      two have been already reported in Polish ruminants recently, while AHSV remains
      absent, however the risk of its emergence has been increasing in the recent
      years. In order to establish the activity of potential AHSV vector at vicinity of
      horses, an OVI midge trap has been placed at the horse stables in the
      southeastern Poland. Another trap has been placed 7 km away at the cattle farm.
      The collections were carried over the midge activity season from April until
      November 2016. The midge abundances at both sites were comparable with the total
      numbers of insects trapped of 43,153 and 34,829 at the cattle and horse farm,
      respectively. Midges belonging to C. obsoletus/scoticus complex were the dominant
      ones at both locations. The other most abundant species were C. punctatus and C.
      pulicaris, while the other ten species identified (C. chiopterus, C. deltus, C.
      dewulfi, C. fagineus, C. impunctatus, C. newsteadi, C. nubeculosus, C. parroti,
      C. riethi, C. stigma) accounted for less than 0.5%. The study has shown that the
      Orbivirus vectors are present at a high abundance at the Polish horse farm, what
      may be a helpful tool in the AHS risk assessment in the nonendemic part of
      Europe.

PMID- 29035853
TI  - The gastrointestinal nematodes of Paramelomys lorentzii and Mammelomys spp.
      (Rodentia: Muridae) with descriptions of a new genus and three new species
      (Heligmonellidae) from Papua New Guinea and Indonesia.
AB  - Unidentified cestodes and 14 species of nematode and larvae that could not be
      placed to family level, were collected from the digestive tracts of 27
      individuals of Paramelomys lorentzii, four of Mammelomys lanosus and a single M.
      rattoides from Papua New Guinea and Papua Indonesia. Of these three were new
      species. Hughjonestrongylus woolleyae sp. nov. can be distinguished from its
      congeners in having up to 26 ridges in the synlophe and a dissymmetric dorsal
      ray. Parvinema bafunminensis gen. nov., sp. nov. can be distinguished from all
      other genera in the family by the combination of features in the synlophe; with a
      carene, up to 17 ridges, and the pattern of ridge sizes. Parvinema helgeni sp.
      nov. differs from P. bafunminensis in the length of the spicule and the number of
      eggs in the uterus. The nematode assemblage of P. lorentzii had similar species
      richness to, and was also dominated by heligmonellids, as that of Paramelomys
      rubex, although the two assemblages differed in species composition.

PMID- 29035854
TI  - Genotyping of Acanthamoeba spp. from water sources from Northwestern Iran.
AB  - Acanthamoeba spp. are free-living amoebae which are ubiquitously distributed
      worldwide and can be found in the wide range of environments, particularly in
      various types of water sources, where they able to cause important health
      problems. In the present study, cultures containing Acanthamoeba from water
      samples were obtained from our earlier survey. For an analysis of the genetic
      pattern of Acanthamoeba isolates, DNA sequencing of nuclear small-subunit rRNA
      gene (18S rRNA or Rns) was applied. A phylogenetic analyses of the isolates
      displayed that all of them were belonged to the potentially pathogenic T4
      genotype. This investigation provides further evidence that the T4 genotype is
      the most prevalent in water samples and demonstrates that there is a need for
      taking more consideration to water sources in order to prevent complications
      associated with pathogenic Acanthamoeba spp.

PMID- 29035855
TI  - Transovarial persistence of Babesia ovata DNA in a hard tick, Haemaphysalis
      longicornis, in a semi-artificial mouse skin membrane feeding system.
AB  - Bovine piroplasmosis, a tick-borne protozoan disease, is a major concern for the
      cattle industry worldwide due to its negative effects on livestock productivity.
      Toward the development of novel therapeutic and vaccine approaches, tick-parasite
      experimental models have been established to clarify the development of parasites
      in the ticks and the transmission of the parasites by ticks. A novel tick-Babesia
      experimental infection model recently revealed the time course of Babesia ovata
      migration in its vector Haemaphysalis longicornis, which is a dominant tick
      species in Japan. However, there has been no research on the transovarial
      persistence of B. ovata DNA using this experimental infection model. Here we
      assessed the presence of B. ovata DNA in eggs derived from parthenogenetic H.
      longicornis female ticks that had engorged after semi-artificial mouse skin
      membrane feeding of B. ovata-infected bovine red blood cells. The oviposition
      period of the engorged female ticks was 21-24 days in the semi-artificial
      feeding. Total egg weight measured daily reached a peak by day 3 in all female
      ticks. Nested PCR revealed that 3 of 10 female ticks laid B. ovata DNA-positive
      eggs after the semi-artificial feeding. In addition, B. ovata DNA was detected at
      the peak of egg weight during oviposition, indicating that B. ovata exist in the
      eggs laid a few days after the onset of oviposition in the tick. These findings
      will contribute to the establishment of B. ovata-infected H. longicornis colonies
      under laboratory conditions.

PMID- 29035856
TI  - Apparent isocitrate lyase activity in Leishmania amazonensis.
AB  - Early reports have demonstrated the occurrence of glyoxylate cycle enzymes in
      several Leishmania species. However, these results have been underestimated
      because genes for the two key enzymes of the cycle, isocitrate lyase (ICL) and
      malate synthase (MS), are not annotated in Leishmania genomes. We have re
      examined this issue in promastigotes of Leishmania amazonensis. Enzyme activities
      were assayed spectrophotometrically in cellular extracts and characterized
      partially. A 40 kDa band displaying ICL activity was visualized on zymograms of
      the extracts. By immunoblotting with mouse antibodies against ICL from Bacillus
      stearothermophilus, a band of approximately 40 kDa was identified, coincident
      with the relative molecular mass of the activity band revealed on zymograms.
      Indirect immunofluorescence of intact promastigotes showed that the recognized
      antigen is distributed as a punctuated pattern, mainly distributed beneath the
      subpellicular microtubules, over a diffused cytoplasmic stain. These results
      clearly demonstrate the existence of an apparent ICL activity in L. amazonensis
      promastigotes, which is associated to a 40 kDa polypeptide and distributed both
      diffused and as punctuate aggregates in the cytoplasm. The relevance of this
      activity is discussed.

PMID- 29035857
TI  - Humoral response of mice infected with Toxocara canis following different
      infection schemes.
AB  - The study was focused on the dynamics of humoral response to Toxocara canis
      excretory-secretory antigens (TES antigens) in mice experimentally infected by T.
      canis L3 larvae in different ways. In particular, we compared the effect of
      infection with two doses of 1000 larvae vs. repeated infections with a low number
      of larvae (daily infection with 10 larvae and weekly infection with 100 larvae in
      the course of 22 weeks). In ELISA, all infections, including both schemes with
      lower larval doses, elicited significant antibody response. Elevated levels of
      total IgE and TES-antigen-specific IgM were detected on day 12 after the first
      infection, followed by IgG and IgG1, and later by IgG3, IgG2a and IgG2b; specific
      IgE response was not detected. It seems that the high levels of IgM and IgG1
      represent the best markers of infection. In addition, gradual increase of IgG2a
      and IgG2b could help in determination of the infection course. As a byproduct of
      our work, a new method of infection by repeated drinking of larvae was
      introduced; it minimizes the pain and discomfort for the experimental mice.

PMID- 29035858
TI  - Detection of small number of Giardia in biological materials prepared from stray
      dogs.
AB  - Giardia lamblia is an intestinal protozoa with intermittent and low shedding
      especially in dogs, and the detection of Giardia is accompanied with problems
      such as sampling and diagnostic method. The objective of this study was to
      detection of Giardia in biological materials with low number of parasite using
      parasitological and molecular methods, and also to determine whether the examined
      stray dogs harbor known zoonotic genotype of Giardia. For this aim 85 fecal and
      duodenal samples were studied from which 1 was positive by Trichrome staining of
      stool, 4 were positive by staining of duodenal samples. The nested PCR analysis
      with primers derived from 18 SrRNA showed that the specific PCR product could be
      amplified in 4 stool and 4 duodenal samples. All positive samples in staining
      analysis were also positive in nested PCR. No amplification could be observed by
      nested PCR with primers derived from beta giardin gene due to the single copy of
      gene. Interestingly, the extracted DNA from old fixed stained Giardia positive
      smears could be also amplified with primers derived from 18SrRNA gene. The
      sequence analysis of nested PCR products showed that they belong to the genotype
      D. In conclusion, it is to denote that the Trichrome or Giemsa methods were not
      suitable for the detection of small number of this parasite in stool and the
      nested PCR with primers derived from 18S rRNA gene can replace the traditional
      methods successfully. For detection of Giardia in stool, primers derived from
      beta giardin will not be recommended.

PMID- 29035859
TI  - Gastrointestinal nematodes infections and anthelmintic resistance in grazing
      sheep in the Eastern Inner Mongolia in China.
AB  - Gastrointestinal nematodes (GIN) are a crucial restraint to grazing sheep
      production worldwide. This study was conducted to determine the infections and
      anthelmintic resistance (AR) of GIN in pasture-based sheep in the Eastern Inner
      Mongolia, China. GIN eggs were tested from 600 grazing sheep feces of 10 farms
      using saturated saline flotation method and McMaster's method. The egg hatch test
      (EHT) and the faecal egg count reduction test (FECRT) were used to evaluate
      resistance of GIN to anthelmintics. We found that the average infection rate was
      79.2% (range: 45%-100%). The grand mean faecal egg count (FEC) was 1813.2 eggs
      per gram (EPG) (range: 0-32400 EPG). There were significant differences in GIN
      infection among different breeds of sheep. The sequence of infection intensity
      and infection rate were Small fat tail > Ujimqin > Ju Ud (p<0.05). The 50%
      effective doses (ED50) of albendazole(ABZ) and levamisole (LMS) for expelling
      were 5.670 ug/mL and 0.302 ug/mL, respectively. The percentage reductions of
      avermectin (AVM), ivermectin (IVM), ABZ and LMS were 81.28%, 86.49%, 76.21% and
      96.59%, respectively. The most predominant parasite genus in all four
      anthelmintics was Haemonchus. In these tested areas, mixed infections of GIN in
      grazing sheep were very common. AR, especially in Haemonchus, was a serious
      problem in these sheep flocks. Thus, actions are urgently required to taken to
      mitigate the worsening situation.

PMID- 29035860
TI  - Expansion of Ashworthius sidemi in red deer and roe deer from the Lower Silesian
      Wilderness and its impact on infection with other gastrointestinal nematodes.
AB  - Nematodes Ashworthius sidemi are typical parasites of Asiatic cervids, mostly
      sika deer (Cervus nippon). Migrating red deer have probably introduced this
      parasite to the area of Poland from neighbouring countries. The aim of the study
      was to determine prevalence and intensity of infection of red deer and roe deer
      from the Lower Silesian Wilderness with A. sidemi after one year from previous
      studies and to examine the influence of these parasites on other species of
      gastrointestinal nematodes. 31 abomasa of red deer and 3 abomasa of roe deer from
      Forest Dictrict of Ruszow have been examined on the presence of parasites. In
      comparison with previous studies, red deer showed significant, over triple
      increase of prevalence of A. sidemi and over fivefold increase of mean intensity
      of infection. Maximum intensity of infection has increased over 24 times. These
      results indicate on dynamic spread of this new aswortiosis foci. Apart from
      previously registered parasite species, four new nematodes have been found in
      examined red deer and roe deer during this year studies. Red deer have been
      infected with Spiculopteragia assymmetrica, typical for fallow deer and
      Haemonchus placei - typical for bovine, whereas roe deer have been infected with
      Trichostrongylus axei and Trichostrongylus capricola, parasites of sheep, goats
      and bovine. Prevalence of red deer infection with nematodes S. boehmi and
      Ostertagia leptospicularis was lower than two years ago while prevalence of
      infection with S. mathevossiani and O. kolchida was higher. Intensity of
      infection with these nematodes has increased.

PMID- 29035861
TI  - The molecular identification of Calodium hepaticum in the wild brown rat (Rattus
      norvegicus) in Poland.
AB  - Calodium hepaticum is a parasitic nematode found primarily in rodents but known
      to infect numerous other mammal species, and causing in humans the hepatic
      calodiasis. Herein, we present the first finding of C. hepaticum in Rattus
      norvegicus in Poland. In this study, we have used the combined pepsin-HCl
      digestion and molecular techniques to detect C. hepaticum infection in the liver.
      The results confirm the usefulness of molecular approaches for investigating the
      biology and epidemiology of C. hepaticum. Additionally in this study, the parts
      of the small subunit rRNA (18S rRNA) gene of Aonchotheca annulosa from bank vole,
      Aonchotheca erinacei and Eucoleus sp. from hedgehog were amplified, yielding the
      first 18S rRNA gene sequences of these Capillariinae nematodes.

PMID- 29035862
TI  - First report of pneumonia caused by Angiostrongylus vasorum in a golden jackal.
AB  - Angiostrongylosis caused by metastrongyloid nematode Angiostrongylus vasorum is
      an emerging parasitic disease in Europe and the red fox (Vulpes vulpes) is
      considered as a main reservoir species for this parasite. Little is known about
      the role of other wild canids in the epidemiology of angiostrongylosis. The
      present paper provides the first description of pathomorphological lesions caused
      by A. vasorum in a golden jackal (Canis aureus). The paper describes a case of co
      infection with A. vasorum and Dirofilaria immitis in a one-year-old female golden
      jackal, legally hunted near the City of Kovin, South Banat, Serbia. The
      postmortem examination revealed severe pneumonia, proliferative endarteritis, the
      presence of two adult males of D. immitis in the right atrium, and the presence
      of 15 adult forms of A. vasorum (11 females and 4 males) in the pulmonary
      arteries. Native microscopy of an impression smear of the lung tissue found
      numerous larvae compatible with the A. vasorum first larval stage. This paper
      provides the first evidence that angiostrongylosis exists in the golden jackal in
      Serbia and confirms that the golden jackal should be considered as a very
      suitable definitive host for A. vasorum. The results suggest the possibility that
      the golden jackal may act as reservoir species and as an important transmitter of
      A. vasorum larvae.

PMID- 29035863
TI  - Sero-detection of Toxocara canis infection in human with T.canis recombinant
      arginine kinase, cathepsin L-1 and TES-26 antigens.
AB  - Three recombinant antigens viz. arginine kinase, cathepsin L-1 and TES-26 of
      Toxocara canis were expressed in Escherichia coli and evaluated for their
      potential in the detection of T. canis larval infection in human in
      immunoglobulin G-enzyme linked immunosorbent assay (IgG-ELISA). Results of the
      IgG-ELISA with the above recombinant antigens were confirmed with commercially
      available IgG detection kit for T. canis infection used as a standard test. All
      three recombinant antigens were 100% sensitive in the detection of positive cases
      (n = 6) of T. canis infection in human and were screened for their cross
      reactivity in human patients with history of Toxoplasma gondii, Plasmodium vivax,
      Entamoeba histolytica, hydatid and hookworm infections. The recombinant TES-26
      antigen showed higher specificity and cross-reacted with T. gondii infection sera
      only. However, arginine kinase and cathepsin L-1 recombinant antigens showed
      cross-reactions with sera of patients infected with T. gondii, P. vivax and E.
      histolytica but not with the patient sera infected with hydatid and hookworm.
      These results show that recombinant TES-26 is a potential diagnostic candidate
      antigen for human toxocarosis caused by migrating T. canis larvae.

PMID- 29035864
TI  - Redescription of the nematode parasites of lizards: Strongyluris oscari
      Travassos, 1923 (Heterakidae) from Brazil and Pharyngodon mamillatus (Linstow,
      1897) (Pharyngodonidae) from Egypt.
AB  - Strongyluris oscari Travassos, 1923, parasite of Topidurus torquatus (Wied
      Neuwied, 1820) (Tropiduridae) from Brazil and Pharyngodon mamillatus (Linstow,
      1897) of Chalcides ocellatus (Forskal, 1775) (Scincidae) from Egypt, were
      redescribed based on light and scanning electron microscopy, and re-evaluation of
      specimens from parasitological collections. The following features were
      accurately observed in S. oscari for the first time: structure of lips and
      pharyngeal valve, presence and distribution of somatic papillae, number and
      arrangement of caudal papillae, presence of inner sclerotised structures
      supporting the ventral sucker and the ventral region in tail of males, and
      structure of the posterior anal lip in females. The unpaired papilla on the
      inferior edge of the ventral sucker in males of S. oscari is a cuticular groove
      instead of a true papilla. Regarding the morphology of P. mamillatus the
      following features were given in details for the first time: structure of the
      cephalic end in both male and female, location of amphids, position of phasmids
      in females and the accurate morphology of caudal bursa in males, including the
      distribution of caudal papillae and the genital cone morphology. Strongyluris
      oscari and P. mamillatus have no intraspecific morphological variations, but wide
      range on biometric features. These variations may be accounted by
      host/environment attributes, since they exhibit wide host and geographical
      spectra. The present results increased the morphological knowledge of P.
      mamillatus and S. oscari, strengthening their taxonomic validity.

PMID- 29035865
TI  - Further study on Physaloptera clausa Rudolphi, 1819 (Spirurida: Physalopteridae)
      from the Amur hedgehog Erinaceus amurensis Schrenk (Eulipotyphla: Erinaceidae).
AB  - In the present study, light and scanning electron microscopy (SEM) were used to
      further study the detailed morphology of Physaloptera clausa Rudolphi, 1819,
      based on the material collected from the Amur hedgehog E. amurensis Schrenk in
      China. The results revealed a few previously unreported morphological features
      and some morphological and morphometric variability between our specimens and the
      previous studies. The present supplementary morphological characters and
      morphometric data could help us to recognize this species more accurately.

PMID- 29035866
TI  - Myrmicinosporidium durum in Poland: a new location for this fungal ant
      endoparasite and updated world distribution.
AB  - Myrmicinosporidium durum is an enigmatic fungal parasite of ants with an unclear
      phylogeny and life cycle. Despite the fact that new records of this fungus have
      been revealed in the last few years; several countries from Eastern Europe still
      lack such information. With this study, we reveal the most northerly location of
      this fungus to date and its first record in Poland a contribution to filling the
      gaps in data about its European distribution. Additionally, we present an updated
      compilation of the world distribution of M. durum and its host ant species.

PMID- 29035867
TI  - Natural occurrence of microsporidia infecting Lepidoptera in Bulgaria.
AB  - We examined 34 lepidopteran species belonging to 12 families to determine
      presence and prevalence of microsporidian pathogens. The insects were collected
      from May 2009 to July 2012 from 44 sites in Bulgaria. Nosema species were
      isolated from Archips xylosteana, Tortrix viridana, Operophtera brumata, Orthosia
      cerasi, and Orthosia cruda. Endoreticulatus sp. was isolated from Eilema
      complana. The prevalence of all isolates in their hosts was low and ranged from
      1.0% to 5.3%. Phylogenetic analyses of the new isolates based on SSU rDNA are
      presented.

PMID- 29035868
TI  - Comparative analysis of codon usage pattern and its influencing factors in
      Schistosoma japonicum and Ascaris suum.
AB  - Schistosoma japonicum and Ascaris suum are considered as the major parasites of
      human which cause various life threatening diseases such as schistomiasis and
      ascariasis. The codon usage bias (CUB) is known as the phenomenon of more usage
      of a specific codon than the other synonymous codons for an amino acid. The
      factors that influence the codon usage bias are mutation pressure, natural
      selection, gene expression, gene length, GC content, RNA stability, recombination
      rates, codon position etc. Here we had used various bioinformatic tools and
      statistical analyses to understand the compositional features, expression level
      and codon usage bias in the genes of these two species.After estimating the
      effective number of codon (ENC) in both the species, codon usage bias was found
      to be low and gene expression was high. The nucleobase A and T were used most
      often than C and G. From neutrality plot and correspondence analysis it was found
      that both natural selection and mutation pressure played an important role in
      shaping the codon usage pattern of both species. Moreover, natural selection
      played a major role while mutation pressure played a minor role in shaping the
      codon usage bias in S. japonicum and A.suum. This is the first report on the
      codon usage biology in S. japonicum and A.suum, and the factors influencing their
      codon usage bias. These results are expected to be useful for genetic engineering
      and evolutionary studies.

PMID- 29035869
TI  - Varroa destructor induces changes in the expression of immunity-related genes
      during the development of Apis mellifera worker and drone broods.
AB  - The ectoparasitic mite Varroa destructor has emerged as the major pest of
      honeybees. Despite extensive research efforts, the pathogenesis of varroosis has
      not been fully explained. Earlier studies suggested that V. destructor
      infestation leads to the suppression of the host's immune system. The aim of this
      study was to analyze the immune responses of 14 genes in the Toll signal
      transduction pathways, including effector genes of antimicrobial peptides (AMPs),
      in developing Apis mellifera workers and drones infested with V. destructor. Four
      developmental stages (L5 larvae, prepupae, and 2 pupal stages) and newly emerged
      imagines were analyzed. In workers, the most significant changes were observed in
      L5 larvae in the initial stages of infestation. A significant increase in the
      relative expression of 10 of the 14 analyzed genes, including defensin-1 and
      defensin-2, was observed in infested bees relative to non-infested individuals.
      The immune response in drones developed at a slower rate. The expression of genes
      regulating cytoplasmic signal transduction increased in prepupae, whereas the
      expression of defensin-1 and defensin-2 effector genes increased in P3 pupae with
      red eyes. The expression of many immunity-related genes was silenced in
      successive life stages and in imagines, and it was more profound in workers than
      in drones. The results indicate that V. destructor significantly influences
      immune responses regulated by the Toll signal transduction pathway in bees. In
      infested bees, the observed changes in Toll pathway genes varied between life
      stages and the sexes.

PMID- 29035870
TI  - Oxidative stress and cytotoxicity elicited lipid peroxidation in hemocytes of
      Bombyx mori larva infested with dipteran parasitoid, Exorista bombycis.
AB  - Parasitization of silkworm, Bombyx mori by invasive larva of dipteran parasitoid
      Exorista bombycis caused upto 20% revenue loss in sericulture. The parasitism was
      successful by suppressing host immune system however mechanism of immune
      suppression induced by E. bombycis is unknown which is unravelled here. The
      infestation induced cytotoxic symptoms in host hemocytes, such as vacuolated
      cytoplasm, porous plasma membrane, indented nuclei with condensed chromatin and
      dilated RER. One of the markers of necrosis is cell permeabilization, which can
      be measured as released lactate dehydrogenase (LDH). LDH level showed
      significantly (P<0.01) high release into extracellular medium in vitro after
      exposure of hemocytes to parasitoid larval tissue protein compared with control
      revealing membrane permeability and loss of cell integrity. At five minutes after
      exposure, cytotoxicity was 43% and was increased to 99% at 3h. The cytotoxicity
      is signalled by increased content of hydrogen peroxide (H2O2) causing lipid
      peroxidation followed by porosity in plasma membrane. A test for lipid
      peroxidation by measurement of lipid peroxidation breakdown product,
      malondialdehyde (MDA) revealed significant increase in peroxidation from one to
      24 h post-invasion, with maximum at 12 h (P<0.008). Level of reactive oxygen
      species measured as H2O2 production increased from 6 to 12 h post-invasion and
      continued to increase significantly (P<0.03) reaching maximum at 48 h. These
      observations reveal that dipteran endoparasitoid invasion induced H2O2 production
      in the hemocytes causing cytotoxicity, lipid peroxidation and membrane porosity
      that suppressed both humoral- and cell-mediated immune responses of hemocytes in
      B. mori.

PMID- 29035871
TI  - Defining the competency of professionalism at two military medical centers.

PMID- 29035873
TI  - Multi-task transfer learning deep convolutional neural network: application to
      computer-aided diagnosis of breast cancer on mammograms.
AB  - Transfer learning in deep convolutional neural networks (DCNNs) is an important
      step in its application to medical imaging tasks. We propose a multi-task
      transfer learning DCNN with the aim of translating the 'knowledge' learned from
      non-medical images to medical diagnostic tasks through supervised training and
      increasing the generalization capabilities of DCNNs by simultaneously learning
      auxiliary tasks. We studied this approach in an important application:
      classification of malignant and benign breast masses. With Institutional Review
      Board (IRB) approval, digitized screen-film mammograms (SFMs) and digital
      mammograms (DMs) were collected from our patient files and additional SFMs were
      obtained from the Digital Database for Screening Mammography. The data set
      consisted of 2242 views with 2454 masses (1057 malignant, 1397 benign). In single
      task transfer learning, the DCNN was trained and tested on SFMs. In multi-task
      transfer learning, SFMs and DMs were used to train the DCNN, which was then
      tested on SFMs. N-fold cross-validation with the training set was used for
      training and parameter optimization. On the independent test set, the multi-task
      transfer learning DCNN was found to have significantly (p  =  0.007) higher
      performance compared to the single-task transfer learning DCNN. This study
      demonstrates that multi-task transfer learning may be an effective approach for
      training DCNN in medical imaging applications when training samples from a single
      modality are limited.

PMID- 29035874
TI  - Parameter selection in limited data cone-beam CT reconstruction using edge
      preserving total variation algorithms.
AB  - There are a number of powerful total variation (TV) regularization methods that
      have great promise in limited data cone-beam CT reconstruction with an
      enhancement of image quality. These promising TV methods require careful
      selection of the image reconstruction parameters, for which there are no well
      established criteria. This paper presents a comprehensive evaluation of parameter
      selection in a number of major TV-based reconstruction algorithms. An appropriate
      way of selecting the values for each individual parameter has been suggested.
      Finally, a new adaptive-weighted projection-controlled steepest descent (AwPCSD)
      algorithm is presented, which implements the edge-preserving function for CBCT
      reconstruction with limited data. The proposed algorithm shows significant
      robustness compared to three other existing algorithms: ASD-POCS, AwASD-POCS and
      PCSD. The proposed AwPCSD algorithm is able to preserve the edges of the
      reconstructed images better with fewer sensitive parameters to tune.

PMID- 29035872
TI  - A review of antimicrobial stewardship training in medical education.
AB  - Objectives: We reviewed the published literature on antimicrobial stewardship
      training in undergraduate and postgraduate medical education to determine which
      interventions have been implemented, the extent to which they have been
      evaluated, and to understand which are most effective. Methods: We searched Ovid
      MEDLINE and EMBASE from inception to December 2016. Four thousand three hundred
      eighty-five (4385) articles were identified and underwent title and abstract
      review. Only those articles that addressed antimicrobial stewardship
      interventions for medical trainees were included in the final review. We employed
      Kirkpatrick's four levels of evaluation (reaction, learning, behaviour, results)
      to categorize intervention evaluations. Results: Our review included 48 articles.
      The types of intervention varied widely amongst studies worldwide. Didactic
      teaching was used heavily in all settings, while student-specific feedback was
      used primarily in the postgraduate setting. The high-level evaluation was sparse,
      with 22.9% reporting a Kirkpatrick Level 3 evaluation; seventeen reported no
      evaluation. All but one article reported positive results from the intervention.
      No articles evaluated the impact of an intervention on undergraduate trainees'
      prescribing behaviour after graduation. Conclusions: This study enhances our
      understanding of the extent of antimicrobial stewardship in the context of
      medical education. While our study demonstrates that medical schools are
      implementing antimicrobial stewardship interventions, rigorous evaluation of
      programs to determine whether such efforts are effective is lacking. We encourage
      more robust evaluation to establish effective, evidence-based approaches to
      training prescribers in light of the global challenge of antimicrobial
      resistance.

PMID- 29035875
TI  - A 20-channel magnetoencephalography system based on optically pumped
      magnetometers.
AB  - We describe a multichannel magnetoencephalography (MEG) system that uses
      optically pumped magnetometers (OPMs) to sense the magnetic fields of the human
      brain. The system consists of an array of 20 OPM channels conforming to the human
      subject's head, a person-sized magnetic shield containing the array and the human
      subject, a laser system to drive the OPM array, and various control and data
      acquisition systems. We conducted two MEG experiments: auditory evoked magnetic
      field and somatosensory evoked magnetic field, on three healthy male subjects,
      using both our OPM array and a 306-channel Elekta-Neuromag superconducting
      quantum interference device (SQUID) MEG system. The described OPM array measures
      the tangential components of the magnetic field as opposed to the radial
      component measured by most SQUID-based MEG systems. Herein, we compare the
      results of the OPM- and SQUID-based MEG systems on the auditory and somatosensory
      data recorded in the same individuals on both systems.

PMID- 29035876
TI  - Hydrogen Gas Attenuates Myocardial Ischemia Reperfusion Injury Independent of
      Postconditioning in Rats by Attenuating Endoplasmic Reticulum Stress-Induced
      Autophagy.
AB  - BACKGROUND/AIMS: To study the effect of inhaling hydrogen gas on myocardial
      ischemic/reperfusion(I/R) injury in rats. METHODS: Seventy male Wistar albino
      rats were divided into five groups at random as the sham group (Sham). The I/R
      group (I/R), The ischemic postconditioning group (IPo), The I/R plus hydrogen
      group (IH2) and the ischemic postconditioning plus hydrogen group (IPoH2). The
      Sham group was without coronary occlusion. In I/R group, Ischemic/reperfusion
      injury was induced by coronary occlusion for 1 hour. Followed by 2 hours of
      reperfusion. In the IPo and IPoH2 group, four cycles of 1 min reperfusion/1 min
      ischemia was given at the end of 1 hour coronary occlusion. While 2% hydrogen was
      administered by inhalation 5 min before reperfusion till 2 hours after
      reperfusion in both the IPoH2 and IH2 group. The heart and blood samples were
      harvested at the end of the surgical protocol. Then the myocardium cell
      endoplasmic reticulum(ER) stress and autophagy was observed by electron
      microscope. In addition, the cardiac ER stress and autophagy related proteins
      expression were detected by Western blotting analysis. RESULTS: Both inhaling 2%
      hydrogen and ischemic postconditioning treatment reduced the ischemic size and
      serum troponin I level in rats with I/R injury, and inhaling hydrogen showed a
      more curative effect compared with ischemic postconditioning treatment. Meanwhile
      inhaling hydrogen showed a better protective effect in attenuating tissue
      reactive oxygen species. Malondialdehyde levels and immunoreactivities against 8
      hydroxy-2'-deoxyguanosine and inhibiting cardiac endoplasmic reticulum stress and
      down-regulating autophagy as compared with ischemic postconditioning treatment.
      CONCLUSION: These results revealed a better protective effect of hydrogen on
      myocardial ischemic/reperfusion injury in rats by attenuating endoplasmic
      reticulum stress and down-regulating autophagy compared with ischemic
      postconditioning treatment.

PMID- 29035877
TI  - Association of Maternal Serum 25-Hydroxyvitamin D Concentrations with Risk of
      Gestational Anemia.
AB  - BACKGROUND/AIMS: Vitamin D deficiency has been shown to be associated with a
      greater prevalence of anemia in various healthy and diseased populations by a
      great deal of observational studies. However, less work has been done to explore
      this association in pregnant women. The aim of this study was to evaluate the
      association between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations
      and risk of gestational anemia in a large, nested case-control study. METHODS:
      The serum 25(OH)D concentrations was measured by enzyme immunoassay in 775
      pregnant women affected with anemia and 1550 controls. Logistic regression
      analysis was conducted to assess the association of 25(OH)D concentrations with
      risk of gestational anemia. RESULTS: We found the 25(OH)D concentrations was
      significantly lower in women affected with anemia than in controls. Logistic
      regression analyses showed that women with 25(OH)D concentrations < 25.0 nmol/L,
      from 25.0 to 37.4 nmol/L and from 37.5 to 49.9 nmol/L all had increased risk of
      anemia when compared with women with concentrations from 50.0 to 74.9 nmol/L. And
      the risk of anemia was significantly increased with the decreasing concentrations
      of the serum 25(OH)D in a dose-dependent manner (P for trend = 0.012). For women
      with concentrations < 50.0 nmol/L, they had an 80% increase in anemia risk (95%
      CI = 1.45-2.25) after adjustment for confounders. We also observed a nonlinear
      relationship between the serum 25(OH)D and anemia, with a threshold for 25(OH)D
      of 50.0 nmol/L existed for anemia. CONCLUSION: Maternal serum 25(OH)D < 50.0
      nmol/L may be a risk factor for gestational anemia, and it should be monitored
      for the high-risk pregnant women.

PMID- 29035878
TI  - Resveratrol Ameliorates Contrast Induced Nephropathy Through the Activation of
      SIRT1-PGC-1alpha-Foxo1 Signaling in Mice.
AB  - BACKGROUND/AIMS: SIRT1 activation promotes the resistance of renal tubular cells
      to oxidative stress, and resveratrol is known as a SIRT1 activator. METHODS:
      Resveratrol was injected intraperitoneally with iohexol for 24 hours. NRK-52E
      cells were pretreated with resveratrol for 24 hours and then exposed to iohexol
      for 3 hours. Renal function was measured by serum creatinine and cell survival
      was assessed by MTT assay. We investigated whether resveratrol attenuates
      oxidative stress and apoptosis in contrast-induced nephropathy (CIN). RESULTS:
      Serum creatinine and tubular injury increased significantly after iohexol
      treatment, and resveratrol co-treatment attenuated the renal injury. Cell
      survival decreased after iohexol exposure and resveratrol reduced cell death
      induced by iohexol. Resveratrol was accompanied with the activation of SIRT1 and
      PGC-1alpha and dephosphorylation of FoxO1 in mice with CIN. SIRT1 and PGC-1alpha
      expression were decreased by iohexol, and increased significantly in resveratrol
      pretreated cells. These processes resulted in reduction of oxidative stress and
      apoptosis both in vivo and in vitro experiments. Resveratrol decreased
      inflammatory cell infiltration induced by iohexol in mice with CIN. SIRT1
      inhibition using siRNA in tubular cells accentuated the decrease of cell
      viability by iohexol. CONCLUSION: Resveratrol attenuated CIN by modulating renal
      oxidative stress and apoptosis through activation of SIRT1-PGC-1alpha-FoxO1
      signaling.

PMID- 29035880
TI  - Immunoregulation of Neutrophil Extracellular Trap Formation by Endothelial
      Derived p33 (gC1q Receptor).
AB  - The formation of neutrophil extracellular traps (NETs) is a host defence
      mechanism, known to facilitate the entrapment and growth inhibition of many
      bacterial pathogens. It has been implicated that the translocation of
      myeloperoxidase (MPO) from neutrophilic granules to the nucleus is crucial to
      this process. Under disease conditions, however, excessive NET formation can
      trigger self-destructive complications by releasing pathologic levels of danger
      associated molecular pattern molecules (DAMPs). To counteract such devastating
      immune reactions, the host has to rely on precautions that help circumvent these
      deleterious effects. Though the induction of DAMP responses has been intensively
      studied, the mechanisms that are used by the host to down-regulate them are still
      not understood. In this study, we show that p33 is an endothelial-derived protein
      that has the ability to annul NET formation. We found that the expression of
      human p33 is up-regulated in endothelial cells upon infections with Streptococcus
      pyogenes bacteria. Using tissue biopsies from a patient with streptococcal
      necrotising fasciitis, we monitored co-localisation of p33 with MPO. Further in
      vitro studies revealed that p33 is able to block the formation of DAMP-induced
      NET formation by inhibiting the enzymatic activity of MPO. Additionally, mice
      challenged with S. pyogenes bacteria demonstrated diminished MPO activity when
      treated with p33. Together, our results demonstrate that host-derived p33 has an
      important immunomodulating function that helps to counterbalance an overwhelming
      DAMP response.

PMID- 29035879
TI  - Advanced Glycation End Products Impair Ca2+ Mobilization and Sensitization in
      Colonic Smooth Muscle Cells via the CAMP/PKA Pathway.
AB  - BACKGROUND/AIMS: Excessive production of advanced glycation end products (AGEs)
      has been implicated in diabetes-related complications. This study aimed to
      investigate the mechanism by which AGEs potentially contribute to diabetes
      associated colonic dysmotility. METHODS: Control and streptozotocin (STZ)-induced
      diabetic groups were treated with aminoguanidine (AG). The colonic transit time
      and contractility of circular muscle strips was measured. ELISA,
      immunohistochemistry and western blotting were used to measure Nepsilon
      carboxymethyl-lysine (CML) levels. Primary cultured colonic smooth muscle cells
      (SMCs) were used in complementary in vitro studies. RESULTS: Diabetic rats showed
      prolonged colonic transit time, weak contractility of colonic smooth muscle
      strips, and elevated levels of AGEs in the serum and colon tissues. cAMP levels,
      protein kinase-A (PKA) activities, and inositol 1,4,5-trisphosphate receptor type
      3 (IP3R3) phosphorylation were increased in the colon muscle tissues of diabetic
      rats, whereas RhoA/Rho kinase activity and myosin phosphatase target subunit 1
      (MYPT1) phosphorylation were reduced. The inhibition of the production of AGEs
      (AG treatment) reduced these effects. In cultured colonic SMCs, AGE-BSA treatment
      increased IP3R3 phosphorylation and reduced intracellular Ca2+ concentration,
      myosin light chain (MLC) phosphorylation, RhoA/Rho kinase activity, and MYPT1
      phosphorylation. The PKA inhibitor H-89 and anti-RAGE antibody inhibited the AGE
      BSA-induced impairment of Ca2+ signaling and cAMP/PKA activation. CONCLUSION:
      AGEs/RAGE participate in diabetes-associated colonic dysmotility by interfering
      with Ca2+ signaling in colonic SMCs through targeting IP3R3-mediated Ca2+
      mobilization and RhoA/Rho kinase-mediated Ca2+ sensitization via the cAMP/PKA
      pathway.

PMID- 29035881
TI  - Activation of Signaling Cascades by Weak Extremely Low Frequency Electromagnetic
      Fields.
AB  - BACKGROUND/AIMS: Results from recent studies suggest that extremely low frequency
      magnetic fields (ELF-MF) interfere with intracellular signaling pathways related
      to proliferative control. The mitogen-activated protein kinases (MAPKs), central
      signaling components that regulate essentially all stimulated cellular processes,
      include the extracellular signal-regulated kinases 1/2 (ERK1/2) that are
      extremely sensitive to extracellular cues. Anti-phospho-ERK antibodies serve as a
      readout for ERK1/2 activation and are able to detect minute changes in ERK
      stimulation. The objective of this study was to explore whether activation of
      ERK1/2 and other signaling cascades can be used as a readout for responses of a
      variety of cell types, both transformed and non-transformed, to ELF-MF. METHODS:
      We applied ELF-MF at various field strengths and time periods to eight different
      cell types with an exposure system housed in a tissue culture incubator and
      followed the phosphorylation of MAPKs and Akt by western blotting. RESULTS: We
      found that the phosphorylation of ERK1/2 is increased in response to ELF-MF.
      However, the phosphorylation of ERK1/2 is likely too low to induce ELF-MF
      dependent proliferation or oncogenic transformation. The p38 MAPK was very
      slightly phosphorylated, but JNK or Akt were not. The effect on ERK1/2 was
      detected for exposures to ELF-MF strengths as low as 0.15 uT and was maximal at
      ~10 uT. We also show that ERK1/2 phosphorylation is blocked by the flavoprotein
      inhibitor diphenyleneiodonium, indicating that the response to ELF-MF may be
      exerted via NADP oxidase similar to the phosphorylation of ERK1/2 in response to
      microwave radiation. CONCLUSIONS: Our results further indicate that cells are
      responsive to ELF-MF at field strengths much lower than previously suspected and
      that the effect may be mediated by NADP oxidase. However, the small increase in
      ERK1/2 phosphorylation is probably insufficient to affect proliferation and
      oncogenic transformation. Therefore, the results cannot be regarded as proof of
      the involvement of ELF-MF in cancer in general or childhood leukemia in
      particular.

PMID- 29035882
TI  - Regulation of Arthritis Severity by the Acid Sphingomyelinase.
AB  - BACKGROUND/AIMS: Rheumatoid arthritis is a chronic autoimmune disease hallmarked
      by inflammation in synovial joints. Treatment is hampered by the lack of a cure
      and current disease-modifying drugs are associated with potentially severe
      toxicities. METHODS: We investigated arthritis severity by measuring joint
      swelling and pro-inflammatory cytokine production in a murine experimental model
      of inflammatory arthritis (antigen-induced arthritis). We analyzed acid
      sphingomyelinase knock-out mice and wild-type littermates, as well as mice
      treated with the pharmacological acid sphingomyelinase inhibitor amitriptyline.
      RESULTS: Genetic ablation or pharmacological inhibition of acid sphingomyelinase
      reduced joint swelling and levels of pro-inflammatory cytokines in the arthritic
      joint. CONCLUSION: We identified acid sphingomyelinase as a novel druggable
      target in rheumatoid arthritis. Functional inhibitors of acid sphingomyelinase
      have been clinically used for decades, are well tolerated and suitable for long
      term treatment. They would be immediately available for clinical development as a
      novel rheumatoid arthritis therapy.

PMID- 29035883
TI  - Association between Allergies and Hypercholesterolemia: A Systematic Review.
AB  - BACKGROUND: There is controversy in the literature regarding the potential
      relationship between atopic predisposition (AP) and serum cholesterol levels. To
      this purpose, we reviewed human studies that investigated this possible link.
      METHODS: Following PRISMA guidelines, a literature search of PubMed and Science
      Direct for peer-reviewed journal articles in English from January 2003, with
      updates through to August 2016, was conducted. Relevant publications were
      reviewed that included pediatric and adult populations. Information on the study
      design, sample, intervention, comparators, outcome, time frame, and risk of bias
      were abstracted for each article. RESULTS: Of 601 reviewed reports, 18 were
      included in this systematic review. Fifteen studies assessed the relationship
      between AP and serum cholesterol levels. Due to the lack both of observational
      and cross-sectional studies from the literature search at this time (only 8
      studies also analyzed confounding factors) there is a high possibility of
      confounding variables (familial and genetic predisposition, age, gender, BMI,
      comorbidity, and medication status) that could not be ruled out. CONCLUSION:
      Existing studies are heterogeneous, making it difficult to draw broad
      conclusions. Future studies and more detailed analyses, considering confounding
      variables and including a larger and homogeneous population, are needed to
      strengthen the argument for a link between lipid metabolism and atopy.

PMID- 29035884
TI  - Protective Effects of Pretreatment with Quercetin Against Lipopolysaccharide
      Induced Apoptosis and the Inhibition of Osteoblast Differentiation via the MAPK
      and Wnt/beta-Catenin Pathways in MC3T3-E1 Cells.
AB  - BACKGROUND/AIMS: Quercetin, a flavonoid found in onions and other vegetables, has
      potential inhibitory effects on bone resorption in vivo and in vitro. In our
      previous study, we found that quercetin treatment reversed lipopolysaccharide
      (LPS)-induced inhibition of osteoblast differentiation through the mitogen
      activated protein kinase (MAPK) pathway in MC3T3-E1 cells. In this study, we
      investigated the underlying mechanisms of pretreatment with quercetin on
      apoptosis and the inhibition of osteoblast differentiation in MC3T3-E1 cells
      induced by LPS. METHODS: MC3T3-E1 osteoblasts were treated with quercetin for 2
      h; cells were then incubated with LPS in the presence of quercetin for the
      indicated times. Cell viability was measured using the Cell Counting Kit-8 (CCK
      8) assay, and cell apoptosis was evaluated using Hoechst 33258 staining. The mRNA
      expression levels of osteoblast-specific genes, Bax and caspase-3 were determined
      by real-time quantitative polymerase chain reaction (qPCR). Protein levels of
      osteoblast-specific genes, caspase-3, Bax, cytochrome c, Bcl-2, Bcl-XL,
      phosphorylated MAPKs and Wnt/beta-catenin were measured using Western blot
      assays. The MAPK and Wnt/beta-catenin signalling pathways were blocked prior to
      pretreatment with quercetin. RESULTS: Pretreatment with quercetin significantly
      restored LPS-suppressed bone mineralization and the mRNA and protein expression
      levels of osteoblast-specific genes such as Osterix (OSX), runt-related
      transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin (OCN)
      in a dose-dependent manner. Pretreatment with quercetin also inhibited osteoblast
      apoptosis, significantly restored the down-regulated expression of Bcl-2 and Bcl
      XL and decreased the upregulated expression of caspase-3, Bax, and cytochrome c
      in MC3T3-E1 cells induced by LPS. Furthermore, pretreatment with quercetin not
      only decreased the abundance of phosphorylated p38 MAPK and increased the
      abundance of phosphorylated extracellular signal regulated kinase (ERK), but also
      triggered the Wnt/beta-catenin pathway through enhancing expression of Wnt3 and
      beta-catenin. Pretreatment with MAPK inhibitors or the Wnt/beta-catenin inhibitor
      XAV939 blocked the protective effects of quercetin against LPS-induced apoptosis
      and the inhibition of osteoblast differentiation. CONCLUSIONS: Our findings
      suggest that pretreatment with quercetin may be a potential drug for preventing
      abnormal human bone loss induced by LPS in bacteria-induced bone diseases.

PMID- 29035885
TI  - ALS-Related Mutant FUS Protein Is Mislocalized to Cytoplasm and Is Recruited into
      Stress Granules of Fibroblasts from Asymptomatic FUS P525L Mutation Carriers.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) shows a strong genetic basis,
      with SOD1, FUS, TARDBP, and C9ORF72 being the genes most frequently involved.
      This has allowed identification of asymptomatic mutation carriers, which may be
      of help in understanding the molecular changes preceding disease onset.
      OBJECTIVES: We studied the cellular expression of FUS protein and the effect of
      heat-shock- and dithiothreitol-induced stress in fibroblasts from FUS P525L
      mutation carriers, healthy controls, and patients with sporadic ALS. METHODS:
      Western blots and immunocytochemistry were performed to study the subcellular
      localization of FUS protein. Control and stressed cells were double stained with
      FUS and the stress marker TIA-R. RESULTS: Fibroblasts from healthy controls and
      sporadic ALS cases showed a prominent nuclear FUS expression. In the 2 FUS P525L
      mutation carriers, instead, most cells showed a protein localization in both
      nucleus and cytoplasm, or exclusively in the cytoplasm. Stress prompted the
      formation of cytoplasmic granules in all subjects and in sporadic ALS FUS
      mislocalization to the cytoplasm. Cytoplasmic FUS was recruited into stress
      granules, which showed a time-dependent decrease in all subjects. However, in the
      FUS P525L fibroblasts, the granules persisted longer, and they were more numerous
      than those detected in the cells from controls and sporadic ALS patients.
      CONCLUSIONS: We show that in fibroblasts of FUS P525L mutation carriers, FUS
      mislocalized to the cytoplasm where it redistributed into stress granules with
      likely a dose effect, i.e. a higher number of cells with granules, which persist
      longer, than in controls and ALS cases. These data represent an early molecular
      change occurring before ALS onset, suggesting a transient preaggregative state.

PMID- 29035886
TI  - Response Gene to Complement-32 Promotes the Imbalance of Treg/Th17 in Patients
      with Dilated Cardiomyopathy.
AB  - BACKGROUND/AIMS: The imbalance of Treg/Th17 cells plays important role in the
      pathogenesis of dilated cardiomyopathy (DCM). Response gene to complement (RGC)
      32 is a cell cycle regulator that plays an important role in cell proliferation.
      We evaluated whether the upregulation of RGC-32 was implicated in the homeostasis
      of Treg/Th17 cells in DCM. METHODS: The levels of plasma RGC-32, IL-17 and TGF
      beta1, and the frequencies of circulating CD4+ RGC-32+ T cells, Th17 and Treg
      cells in patients with DCM were determined by Cytokine-specific sandwich ELISA
      and the flow cytometer (FCM), respectively. RESULTS: A significant elevation of
      plasma RGC-32 in patients with DCM compared with healthy control (HC) subjects
      was observed. This upregulation was associated with an increase in frequency of
      Th17 and a decrease in frequency of Treg cells. To further assessed the role of
      RGC-32, we investigated the effects of RGC-32 up- or down-regulation on
      frequencies of Th17 and Treg cells in peripheral blood mononuclear cells (PBMCs)
      from subjects. Importantly, overexpression of RGC-32 was accompanied by an
      augmentation of Th17 and a reduction of Treg expression. CONCLUSION: In summary,
      our study demonstrated the up-regulation of RGC-32 contributed to the imbalance
      of Treg/Th17 cells in patients with DCM.

PMID- 29035887
TI  - Valeriana officinalis Root Extract Modulates Cortical Excitatory Circuits in
      Humans.
AB  - BACKGROUND: Valeriana officinalis extract (VE) is a popular herbal medicine used
      for the treatment of anxiety and sleep disorders. Although the anxiolytic and
      sedative effects are mainly attributed to the modulation of GABA-ergic
      transmission, the mechanism of action has not been fully investigated in humans.
      Noninvasive brain stimulation protocols can be used to elucidate the mechanisms
      of action of psychoactive substances at the cortical level in humans. In this
      study, we investigated the effects of a single dose of VE on cortical
      excitability as assessed with transcranial magnetic stimulation (TMS). METHODS:
      Fifteen healthy volunteers participated in a double-blind, randomized, cross
      over, placebo-controlled study. Subjects were required to take either 900 mg of
      VE (valerenic acid 0.8%) or placebo (an equal dose of vitamin E). Motor cortex
      excitability was studied by single and paired TMS before and at 1 h and 6 h after
      the oral administration. Cortical excitability was assessed using different TMS
      parameters: resting motor threshold, motor-evoked potential amplitude, cortical
      silent period, short-interval intracortical inhibition, and intracortical
      facilitation. Furthermore, we assessed sensorimotor integration by short-latency
      and long-latency afferent inhibition. RESULTS: We found a significant reduction
      in ICF, without any significant changes in other TMS measures of motor cortex
      excitability. The amount of ICF returned to baseline value 6 h after the intake
      of the VE. CONCLUSION: A single oral dose of VE modulates intracortical
      facilitatory circuits. Our results in healthy subjects could be predictive
      markers of treatment response in patients and further support the use of pharmaco
      TMS to investigate the neuropsychiatric effects of herbal therapies in humans.

PMID- 29035888
TI  - Nitric Oxide Mediates Insect Cellular Immunity via Phospholipase A2 Activation.
AB  - After infection or invasion is recognized, biochemical mediators act in signaling
      insect immune functions. These include biogenic amines, insect cytokines,
      eicosanoids, and nitric oxide (NO). Treating insects or isolated hemocyte
      populations with different mediators often leads to similar results. Separate
      treatments with an insect cytokine, 2 biogenic amines, and an eicosanoid lead to
      a single result, hemocyte spreading, understood in terms of intracellular cross
      talk among these signaling systems. This study focuses on the cross-talk between
      NO and eicosanoid signaling in our model insect, Spodoptera exigua. Bacterial
      injection increased NO concentrations in the larval hemocytes and fat body, and
      RNA interference (RNAi) of the S. exigua NO synthase (NOS) gene suppressed NO
      concentrations. RNAi treatment also led to a significant reduction in hemocyte
      nodulation following bacterial injection. Similar RNAi treatments led to
      significantly reduced PLA2 activities in the hemocytes and fat body compared to
      control larvae. Injection of L-NAME also prevented the induction of PLA2 activity
      following bacterial challenge. An injected NO donor, S-nitroso-N-acetyl-DL
      penicillamine, increased PLA2 activity in a dose-dependent manner. However,
      eicosanoids did not influence NO concentrations in immune-challenged larvae. We
      infer that NO and eicosanoid signaling operate via cross-talk mechanisms in which
      the elevated NO concentrations activate PLA2 and eicosanoid biosynthesis, which
      finally mediates various immune responses.

PMID- 29035889
TI  - Inhibition of Suicidal Erythrocyte Death by Volasertib.
AB  - BACKGROUND/AIMS: The Polo-like kinase 1 (Plk1) inhibitor volasertib is used in
      the treatment of malignancy. Volasertib is partially effective by triggering
      suicidal death or apoptosis of tumor cells. Similar to apoptosis of nucleated
      cells, erythrocytes may enter suicidal cell death or eryptosis, which is
      characterized by cell membrane scrambling with phosphatidylserine translocation
      to the cell surface and by cell shrinkage. Stimulators of eryptosis include
      energy depletion, hyperosmotic shock, oxidative stress and excessive increase of
      cytosolic Ca2+ activity ([Ca2+]i). The present study explored, whether volasertib
      impacts on eryptosis. METHODS: Human erythrocytes have been exposed to energy
      depletion (glucose withdrawal for 48 hours), hyperosmotic shock (addition of 550
      mM sucrose for 6 hours), oxidative stress (addition of 0.3 mM tert
      butylhydroperoxide [tBOOH] for 50 min) or Ca2+ ionophore ionomycin (1 uM for 60
      min) in absence and presence of volasertib (0.5-1.5 ug/ml) and flow cytometry was
      employed to quantify phosphatidylserine exposure at the cell surface from annexin
      V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3 fluorescence,
      reactive oxygen species from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA)
      fluorescence and ceramide abundance utilizing antibodies. For comparison, annexin
      V-binding and forward scatter were determined following a 48 hours exposure of
      human leukemic K562 cells in RPMI-1640 medium to volasertib. RESULTS: Treatment
      with volasertib alone did not significantly modify annexin-V-binding or forward
      scatter in mature erythrocytes. Energy depletion, hyperosmotic shock, oxidative
      stress and ionomycin, all markedly and significantly increased the percentage of
      annexin-V-binding erythrocytes, and decreased the forward scatter. Volasertib
      significantly blunted the effect of energy depletion and hyperosmotic shock, but
      not of oxidative stress and ionomycin on annexin-V-binding. Volasertib did not
      significantly influence the effect of any maneuver on forward scatter. In K562
      cells, volasertib enhanced annexin-V-binding and decreased the forward scatter.
      CONCLUSIONS: Volasertib is a novel inhibitor of erythrocyte cell membrane
      scrambling following energy depletion and hyperosmotic shock, effects contrasting
      the stimulation of K562 cell apoptosis.

PMID- 29035890
TI  - Biocharacterization of Heat Shock Protein 90 in Acetaminophen-Treated Livers
      Without Conspicuous Drug Induced Liver Injury.
AB  - BACKGROUND/AIMS: Acetaminophen (APAP) refers to a medication used to manage pain
      and fever symptoms. Heat shock protein 90 (Hsp90) is to be expressed during
      various stresses, such as wound healing and tissue remodeling. Recently, it is
      discovered that Hsp90 is a potential modifier of cytogenesis. In comparison to
      clinical references of liver damage, this study was designed to assess the
      potential bioeffect of Hsp90 in APAP-treated livers without conspicuous drug
      induced liver injury (DILI). METHODS: In our current study, human plasma samples
      of APAP-used patients were collected for biochemical assays in clinical
      parameters. Adult male mice were used to investigate the biocharacterization of
      Hsp90 in APAP-treated livers through serological tests and immunoassays. Further,
      a mouse liver cell strain was employed in assessment of bioeffect of APAP on
      hepatocellular Hsp90 expression. RESULTS: Correspondingly, the clinical data
      showed APAP-administered patients resulted in increased Hsp90 levels in serum
      when compared to other clinical parameters of liver injury. In adult mice study,
      APAP-treated livers showed unchanged hepatocellular and metabolic functions, as
      highlighted in biochemical analysis and immunoassay. Notably, Hsp90 expression in
      APAP-treated mice were elevated in the serum and liver samples. In quantitative
      western blot assay, the present data suggested that hepatocellular Hsp90 level
      was up-regulated followed by APAP treatment. In mouse cell strain study, APAP
      treated liver cells had increased trend of aminotransferase contents and
      apoptotic counts. Further, endogenous Hsp90 expression in APAP-exposed cells was
      increased dose- and time-dependently. CONCLUSIONS: In conclusion, our current
      findings disclose that Hsp90 biomolecule may be a potential indicator for APAP
      induced inconspicuous DILI, in which it seems to be characterized with more
      sensitive than other diagnosis criteria.

PMID- 29035893
TI  - Ultrasound-guided Lumbar Plexus Block in Supine Position.

PMID- 29035892
TI  - Patent Foramen Ovale as Possible Cause of Sudden Sensorineural Hearing Loss: A
      Case Report.
AB  - OBJECTIVE: To present a case of sudden sensorineural hearing loss (SSNHL) and the
      related diagnostic workup. CLINICAL PRESENTATION AND INTERVENTION: A 54-year-old
      man presented with a unilateral SSNHL episode and vertigo. A severe patent
      foramen ovale (PFO) that included a complete ear nose and throat, audiological,
      and neurological examination was discovered during the diagnostic workup.
      Audiometry, blood, and serological tests were performed. Magnetic resonance
      imaging and color Doppler echography of the supra-aortic trunks and lower limbs
      were carried out. Finally, transthoracic followed by transesophageal
      echocardiography and transcranial Doppler were performed in order to confirm the
      diagnosis of PFO. Medical therapy with systemic steroid and antiplatelet drugs
      was administered. CONCLUSIONS: This case showed a small PFO associated with an
      aneurysmatic interatrial septum. The PFO and paradoxical thromboembolism could be
      involved in the pathogenesis of SSNHL.

PMID- 29035891
TI  - Inhibiting ROS-TFEB-Dependent Autophagy Enhances Salidroside-Induced Apoptosis in
      Human Chondrosarcoma Cells.
AB  - BACKGROUND/AIMS: Autophagy modulation has been considered a potential therapeutic
      strategy for human chondrosarcoma, and a previous study indicated that
      salidroside exhibits significant anti-carcinogenic activity. However, the ability
      of salidroside to induce autophagy and its role in human chondrosarcoma cell
      death remains unclear. METHODS: We exposed SW1353 cells to different
      concentrations of salidroside (0.5, 1 and 2 mM) for 24 h. RT-PCR, Western
      blotting, Immunocytofluorescence, and Luciferase Reporter Assays were used to
      evaluate whether salidroside activated the TFEB-dependent autophagy. RESULTS: We
      show that salidroside induced significant apoptosis in the human chondrosarcoma
      cell line SW1353. In addition, we demonstrate that salidroside-induced an
      autophagic response in SW1353 cells, as evidenced by the upregulation of LC3-II
      and downregulation of P62. Moreover, pharmacological or genetic blocking of
      autophagy enhanced salidroside -induced apoptosis, indicating the cytoprotective
      role of autophagy in salidroside-treated SW1353 cells. Salidroside also induced
      TFEB (Ser142) dephosphorylation, subsequently to activated TFEB nuclear
      translocation and increase of TFEB reporter activity, which contributed to
      lysosomal biogenesis and the expression of autophagy-related genes. Importantly,
      we found that salidroside triggered the generation of ROS in SW1353 cells.
      Furthermore, NAC, a ROS scavenger, abrogated the effects of salidroside on TFEB
      dependent autophagy. CONCLUSIONS: These data demonstrate that salidroside
      increased TFEB-dependent autophagy by activating ROS signaling pathways in human
      chondrosarcoma cells. These data also suggest that blocking ROS-TFEB-dependent
      autophagy to enhance the activity of salidroside warrants further attention in
      treatment of human chondrosarcoma cells.

PMID- 29035894
TI  - Prevalence of Potentially Distracting Noncare Activities and Their Effects on
      Vigilance, Workload, and Nonroutine Events during Anesthesia Care.
AB  - BACKGROUND: When workload is low, anesthesia providers may perform non-patient
      care activities of a clinical, educational, or personal nature. Data are limited
      on the incidence or impact of distractions on actual care. We examined the
      prevalence of self-initiated nonclinical distractions and their effects on
      anesthesia workload, vigilance, and the occurrence of nonroutine events. METHODS:
      In 319 qualifying cases in an academic medical center using a Web-based
      electronic medical chart, a trained observer recorded video and performed
      behavioral task analysis. Participant workload and response to a vigilance
      (alarm) light were randomly measured. Postoperatively, participants were
      interviewed to elicit possible nonroutine events. Two anesthesiologists reviewed
      each event to evaluate their association with distractions. RESULTS: At least one
      self-initiated distraction was observed in 171 cases (54%), largely during
      maintenance. Distractions accounted for 2% of case time and lasted 2.3 s
      (median). The most common distraction was personal internet use. Distractions
      were more common in longer cases but were not affected by case type or American
      Society of Anesthesiologists physical status. Workload ratings were significantly
      lower during distraction-containing case periods and vigilance latencies were
      significantly longer in cases without any distractions. Three distractions were
      temporally associated with, but did not cause, events. CONCLUSIONS: Both nurse
      anesthetists and residents performed potentially distracting tasks of a personal
      and/or educational nature in a majority of cases. Self-initiated distractions
      were rarely associated with events. This study suggests that anesthesia
      professionals using sound judgment can self-manage nonclinical activities. Future
      efforts should focus on eliminating more cognitively absorbing and less escapable
      distractions, as well as training in distraction management.

PMID- 29035895
TI  - A Large Anterior Mediastinal Mass.

PMID- 29035896
TI  - Intraoperative Phototherapy for Hyperbilirubinemia.

PMID- 29035897
TI  - Images in Anesthesiology: A Clot in Transit: Impending Paradoxical Embolization.

PMID- 29035898
TI  - Intraoral Lipomas.

PMID- 29035899
TI  - Driveline Site Is Not a Predictor of Infection After Ventricular Assist Device
      Implantation.
AB  - Driveline infections (DLIs) remain a major source of morbidity for patients
      requiring long-term ventricular assist device (VAD) support. We aimed to assess
      whether VAD driveline exit site (DLES) (abdomen versus chest wall) is associated
      with DLI. All adult patients who underwent insertion of a HeartWare HVAD or
      HeartMate II (HMII) between 2009 and 2016 were included. Driveline infection was
      defined as clinical evidence of DLI accompanied by a positive bacterial swab and
      need for antibiotics. Competing risks analysis was used to assess the association
      between patient characteristics and DLI. Ninety-two devices (59 HMII) were
      implanted in 85 patients (72 men; median age 57.4 years) for bridge to transplant
      or destination therapy. VAD DLES was chest in 28 (30.4%) devices. Median time on
      VAD support was 347.5 days (IQR 145.5, 757.5), with 28 transplants and 29 deaths
      (27 on device). DLI occurred in 24 patients (25 devices) at a median of 140 days
      (IQR 67, 314) from implant. Staphylococcus aureus accounted for 15 infections
      (60%). Freedom from infection was 72.8% (95% confidence interval [CI] 53.1-78.0%)
      at 1 year and 41.9% (95% CI 21.1-61.5%) at 3 years. In competing risks
      regression, abdominal DLES was not predictive of DLI (hazard ratio, HR 1.65 [95%
      CI 0.63, 4.29]), but body mass index (BMI) >30 kg/m was (HR 2.72 [95% CI 1.25,
      5.92]). In conclusion, risk of DLI is high among patients on long-term VAD
      support, and a nonabdominal DLES does not reduce this risk. The only predictor of
      DLI in this series was an elevated BMI.

PMID- 29035900
TI  - CE: Original Research: Primary Care Providers and Screening for Military Service
      and PTSD.
AB  - : : Background: Most veterans have the option of receiving their health care from
      the Veterans Health Administration or through primary care providers in the
      private sector. However, there is some evidence that fewer than half of community
      based, private sector primary care and mental health providers screen their
      patients for military service, particularly in rural areas, leaving these
      veterans less likely to be screened for posttraumatic stress disorder (PTSD) and
      other military service-related conditions. PURPOSE: To determine whether primary
      care providers in the private sector are screening patients for military service
      and subsequent PTSD. METHODS: We designed and piloted a survey to determine
      whether primary care providers in a rural Pennsylvania region routinely screen
      for military service and service-related PTSD. We distributed the survey to a
      convenience sample of more than 250 primary care providers in central and western
      Pennsylvania through the U.S. Postal Service, via Facebook, and via work e-mails
      for those who worked in a local health system. RESULTS: Among 50 eligible
      respondents, only four (8%) said they screen all their patients for military
      service, and 20 (40%) reported screening none; only two respondents (4%) screened
      all their patients who have served in the military for PTSD, and 30 (60%)
      screened none. CONCLUSION: Veterans who rely on private sector providers may not
      receive evidence-based care for military service-related health problems,
      including PTSD. To improve care for these patients, providers in the private
      sector should be educated on why all patients should be screened for military
      service, how to conduct such screening properly, and veterans' general health
      concerns.

PMID- 29035901
TI  - CE: Preeclampsia: Current Approaches to Nursing Management.
AB  - : Preeclampsia, one of four hypertensive disorders of pregnancy, has
      traditionally been characterized as new-onset hypertension and proteinuria
      developing after 20 weeks' gestation. It is, however, now understood to be a
      complex, progressive, multisystem disorder with a highly variable presentation
      and a number of potentially life-threatening complications. The American College
      of Obstetricians and Gynecologists Task Force on Hypertension in Pregnancy has
      refined preeclampsia diagnostic criteria accordingly, and as the disorder's
      pathogenesis has been more clearly defined, new targets for screening, diagnosis,
      prevention, and treatment have emerged. This clinical update provides a review of
      current practice related to preeclampsia risk assessment, prediction, and
      management. It discusses preeclampsia pathophysiology and points readers to
      valuable health care resources on the topic.

PMID- 29035902
TI  - Comparison of Direct Patient Care Costs and Quality Outcomes of the Teaching and
      Nonteaching Hospitalist Services at a Large Academic Medical Center.
AB  - PURPOSE: To compare costs of care and quality outcomes between teaching and
      nonteaching hospitalist services, while testing the assumption that resident
      driven care is more expensive. METHOD: Records of inpatients with the top 20
      Medicare Severity Diagnosis-Related Groups admitted to the University Teaching
      Service (UTS) and nonteaching hospitalist service (NTHS) at Houston Methodist
      Hospital from 2014-2015 were analyzed retrospectively. Direct costs of care,
      length of stay (LOS), in-hospital mortality (IHM), 30-day readmission rate
      (30DRR), and consultant utilization were compared between the UTS and NTHS.
      Propensity score matching and case mix index (CMI) were used to mitigate
      differences in baseline characteristics. To compare outcomes between matched
      groups, the Wilcoxon rank sum test and chi-square test were used. A sensitivity
      analysis was conducted using multivariable regression analysis. RESULTS: From the
      overall study population of 8,457 patients, 1,041 UTS and 3,123 NTHS patients
      were matched. CMI was 1.07 for each group. The UTS had lower direct costs of care
      per case ($5,028 vs. $5,502, P = .006), lower LOS (4.7 vs. 5.2 days, P = .0002),
      and lower consultant utilization (1.0 vs. 1.6, P <= .0001) versus the NTHS. The
      UTS and NTHS 30DRR (17.2% vs. 19.3%, P = .110) and IHM (2.9% vs. 3.7%, P = .206)
      were comparable. The multivariable regression analysis validated the matched data
      and identified an incremental cost savings of $333/UTS patient. CONCLUSIONS:
      Patients of an academic hospitalist service had significantly shorter LOS, fewer
      consultants, and lower direct care costs than comparable patients of a
      nonteaching service.

PMID- 29035903
TI  - The Future of Obstetrics and Gynecology: MACRA, Electronic Health Records, and
      More.
AB  - There is immense change affecting obstetrical and gynecologic medical practice at
      this moment in time-involving reimbursement with the shift from volume-based to
      value-based care, increasing regulation, and workforce sustainability. Aspects to
      be reviewed in this chapter include reimbursements and Medicare Access and CHIP
      Reauthorization Act of 2015 (MACRA), electronic medical records, physician
      satisfaction surveys, maintenance of certification, and physician burnout.

PMID- 29035904
TI  - Improvement in cognitive abilities following cabergoline treatment in patients
      with a prolactin-secreting pituitary adenoma.
AB  - Hyperprolactinaemia may affect sexual and reproductive functioning. However,
      recent studies suggest that increased prolactin levels may also have negative
      effects on cognition. We aimed to study whether the reduction in prolactin levels
      by cabergoline in patients with hyperprolactinaemia is followed by an improvement
      in cognitive tasks. We studied seven patients with hyperprolactinaemia caused by
      a prolactinoma that had an indication to start treatment with cabergoline. All
      patients were assessed twice (baseline and 6-12 months after cabergoline
      treatment) with a cognitive battery. Plasma prolactin levels were determined. We
      found a significant improvement in the speed of processing, working memory,
      visual learning and reasoning and problem-solving domains after cabergoline
      treatment. Improvements in speed of processing and reasoning and problem solving
      were greater in patients with baseline prolactin levels above the median. In
      summary, a reduction in prolactin levels by cabergoline in patients with
      hyperprolactinaemia is followed by an improvement in cognitive abilities. This
      finding suggests that prolactin may be involved in cognitive processes, although
      cabergoline could also have procognitive effects that are independent of
      prolactin changes. Further clinical trials are needed to confirm the potential
      cognitive-enhancement properties of cabergoline in patients with chronic
      hyperprolactinaemia.

PMID- 29035905
TI  - Hospital-Community Partnerships to Aid Transitions for Older Adults: Applying the
      Care Transitions Framework.
AB  - This study examined the implementation and hospitalwide scaling of a community
      based transitional care program to reduce readmissions among adults 65 years or
      older. Our analysis was guided by the Care Transitions Framework and was based on
      semistructured interviews with program implementers to identify intervention
      successes, barriers, and outcomes beyond reducing readmissions. Such outcomes
      included the program's critical role in providing a safety net and transition to
      more advanced care, and redefining intervention success from more patient
      centered perspectives.

PMID- 29035906
TI  - Effectiveness of a Multifaceted Delirium Screening, Prevention, and Treatment
      Initiative on the Rate of Delirium Falls in the Acute Care Setting.
AB  - Delirium is a potentially modifiable fall risk factor, but few studies address
      the effects of delirium programs on falls. Beginning in 2011, we implemented a
      nursing-driven hospitalwide delirium program targeting improvements in risk
      identification, prevention, detection, and treatment. Over the course of the
      program, delirium falls decreased from 0.91 to 0.50 per patient day (P = .0002).
      A decrease in overall falls was also noted (P = .0007).

PMID- 29035908
TI  - Infantile Myofibroma of the Carotid Space Presenting as Horner Syndrome.

PMID- 29035910
TI  - New predictive factors of poor response to therapy in autoimmune hepatitis: role
      of mean platelet volume.
AB  - BACKGROUND AND OBJECTIVES: The response to immunosuppressive therapy in
      autoimmune hepatitis (AIH) is a matter of debate. The aim of this work is to
      identify the histological, biochemical, and clinical predictive factors of
      incomplete response/treatment failure to the standard treatment (prednisone with
      or without azathioprine) in a well-characterized series of AIH Egyptian patients.
      PATIENTS AND METHODS: Of 49 AIH patients, only 36 patients completed this
      retrospective cohort study. The immunological, biochemical, histopathological,
      and clinical characteristics of patients were evaluated at diagnosis and during
      follow-up. RESULTS: Patients were classified into two groups; group A showed a
      complete response to therapy (n=22; 61%) and group B showed partial
      response/treatment failure (n=14; 39%). In a multivariate analysis, we observed
      that age at diagnosis up to 22 years [odds ratio (OR): 23.22; confidence interval
      (CI): 3.978-135.549; P<0.001], serum albumin up to 3.2 g/dl (OR: 5.36; CI: 1.237
      23.209; P=0.025), mean platelet volume (MPV) of at least 10.75 fl (OR: 16.5; CI:
      3.093-88.037; P<0.001), and presence of cirrhosis at diagnosis (OR: 8.44; CI:
      1.682-42.392; P=0.001) were independent variables that can predict partial
      response/treatment failure. MPV correlated positively with stages of
      fibrosis/cirrhosis and grades of activity in liver biopsy at diagnosis and
      correlated inversely with serum albumin and age at presentation. During therapy,
      group B showed a fluctuation in MPV levels, however, group A showed a progressive
      decline until the end point. CONCLUSION: Our study confirmed that younger age,
      hypoalbuminemia, increased MPV, and cirrhosis at diagnosis were all independent
      predictors of incomplete response/treatment failure in AIH patients. MPV may
      reflect the response to therapy.

PMID- 29035911
TI  - Ab Interno Gel Implant for the Treatment of Glaucoma Patients With or Without
      Prior Glaucoma Surgery: 1-Year Results.
AB  - PURPOSE: The purpose of this study is to evaluate IOP lowering effects and
      complication management of an ab interno gel implant for the treatment of
      patients refractory to antiglaucoma medication or glaucoma surgery. METHODS:
      Retrospective analysis of the medical records of 242 consecutive eyes of 146
      patients with uncontrolled intraocular pressure (IOP) despite maximum tolerated
      medical therapy or prior surgical intervention that underwent XEN45 implantation
      (as sole procedure or in combination with cataract surgery) between March 2014
      and June 2015. Data included IOP, number of glaucoma medications, the need for
      additional surgery, needling, and complications. RESULTS: During the study
      period, mean IOP had decreased by 54.1% from 32.19 (+/-9.1) mm Hg to 14.24 (+/
      4.0) mm Hg (P=0.00; Wilcoxon test). The number of antiglaucoma medications had
      decreased from a mean of 3.13+/-1.0 to 0.3+/-0.7 (P=0.00; Wilcoxon test).
      Needling was required between week 1 and months 3 in 27.7% of all eyes to enhance
      the outflow. Hypotony (IOP<6 mm Hg) was observed in 9 eyes (4.0%) at 1 month but
      normalized in all eyes at 12 months postoperatively. Two eyes experienced
      hypotony requiring the refill of the anterior chamber. CONCLUSIONS: Our data
      indicate that the XEN45 gel implant has a favorable safety profile and is an
      effective treatment option for controlling IOP in glaucoma patients with
      unregulated IOP despite IOP lowering medical therapy or prior surgical
      intervention. It offers an effective approach, both as sole procedure and in
      combination with cataract surgery.

PMID- 29035912
TI  - Surgical Outcomes of Gonioscopy-assisted Transluminal Trabeculotomy (GATT) in
      Patients With Open-angle Glaucoma.
AB  - PURPOSE: To evaluate the efficacy and safety of gonioscopy-assisted transluminal
      trabeculotomy (GATT) in patients with open-angle glaucoma. PARTICIPANTS AND
      METHODS: A retrospective chart review of adult patients who underwent GATT due to
      inadequately controlled intraocular pressure (IOP) or intolerance to medication.
      Main outcome measures were success rate, IOP, and number of glaucoma medications.
      Success was defined as IOP reduction >20% from baseline or IOP between 5 to 21 mm
      Hg, and no need for further glaucoma surgery. When success criteria were not met
      for any postoperative visit >3 months after surgery, failure was determined.
      RESULTS: In total, 66 patients, average age 62.9+/-14.9 years (50.8% female) were
      included in the analysis. Average follow-up was 11.9 months (range, 3 to 30 mo)
      and overall success rate was 63.0%. Mean IOP was 26.1+/-9.9 mm Hg preoperatively
      and 14.6+/-4.7 mm Hg at 12 months (44% IOP decrease; P<0.001). Mean number of
      medications decreased from 3.1+/-1.1 preoperatively to 1.2+/-0.9 at 12 months
      (P<0.001). No significant differences between patients with primary open-angle
      glaucoma and other types of glaucoma were found.The rate of hyphema at 1 week and
      1 month postoperatively was 38% and 6%, respectively. Overall GATT success rate
      among white and black patients was 69% and 42%, respectively, which was
      statistically significant (P<0.05). CONCLUSIONS: The future of GATT as a
      minimally invasive glaucoma surgery in adults seems promising. This position is
      supported by its low rate of long-term complications and the conjunctiva-sparing
      nature of the surgery.

PMID- 29035909
TI  - Dysregulated myelopoiesis and hematopoietic function following acute physiologic
      insult.
AB  - PURPOSE OF REVIEW: The purpose of this review is to describe recent findings in
      the context of previous work regarding dysregulated myelopoiesis and
      hematopoietic function following an acute physiologic insult, focusing on the
      expansion and persistence of myeloid-deriver suppressor cells, the deterioration
      of lymphocyte number and function, and the inadequacy of stress erythropoiesis.
      RECENT FINDINGS: Persistent myeloid-derived suppressor cell (MDSC) expansion
      among critically ill septic patients is associated with T-cell suppression,
      vulnerability to nosocomial infection, chronic critical illness, and poor long
      term functional status. Multiple approaches targeting MDSC expansion and
      suppressor cell activity may serve as a primary or adjunctive therapeutic
      intervention. Traumatic injury and the neuroendocrine stress response suppress
      bone marrow erythropoietin receptor expression in a process that may be reversed
      by nonselective beta-adrenergic receptor blockade. Hepcidin-mediated iron
      restricted anemia of critical illness requires further investigation of novel
      approaches involving erythropoiesis-stimulating agents, iron administration, and
      hepcidin modulation. SUMMARY: Emergency myelopoiesis is a dynamic process with
      unique phenotypes for different physiologic insults and host factors. Following
      an acute physiologic insult, critically ill patients are subject to persistent
      MDSC expansion, deterioration of lymphocyte number and function, and inadequate
      stress erythropoiesis. Better strategies are required to identify patients who
      are most likely to benefit from targeted therapies.

PMID- 29035913
TI  - The Water-drinking Test and Glaucoma Progression: Considerations Regarding the
      Test Usefulness as an Independent Risk Assessment Tool.

PMID- 29035914
TI  - Extracorporeal Membrane Oxygenation Is First-Line Therapy for Acute Respiratory
      Distress Syndrome.

PMID- 29035915
TI  - The shape of things to come in lipid management: a feast of reason.

PMID- 29035916
TI  - Observe to get pain relief: current evidence and potential mechanisms of socially
      learned pain modulation.

PMID- 29035918
TI  - Dopaminergic mechanisms in periaqueductal gray-mediated antinociception.
AB  - As important as perceiving pain is the ability to modulate this perception in
      some contextual salient situations. The periaqueductal gray (PAG) is perhaps the
      most important site of endogenous pain modulation; however, little is known about
      dopaminergic mechanisms underlying PAG-mediated antinociception. In this study,
      we used a pharmacological approach to evaluate this subject. We found that u
      opioid receptor-induced antinociception (DAMGO, 0.3 MUg) from PAG was blocked by
      the coadministration of either D1-like or D2-like dopaminergic antagonists
      (SCH23390, 2, 4, and 6 MUg or raclopride, 2 and 4 MUg, respectively) both in the
      tail-flick and in the mechanical paw-withdrawal test. A selective D2-like
      receptor agonist (piribedil, 6 and 12 MUg into the PAG) induced antinociception
      in the mechanical paw-withdrawal test, but not in the tail-flick test. This
      effect was blocked by the coadministration of its selective antagonist
      (raclopride 4 MUg), as well as by either a GABAA agonist (muscimol, 0.1 MUg) or
      an opioid receptor antagonist (naloxone, 0.5 MUg). A selective D1-like receptor
      agonist (SKF38393, 1, 5, and 10 MUg into the PAG) induced a poor and transient
      antinociceptive effect, but when combined with piribedil, a potentiated
      antinociceptive effect emerged. None of these treatments affected locomotion in
      the open-field test. These findings suggest that u-opioid antinociception from
      the PAG depends on dopamine acting on both D1-like and D2-like receptors.
      Selective activation of PAG D2-like receptors induces antinociception mediated by
      supraspinal mechanisms dependent on inhibition of GABAA and activation of opioid
      neurotransmission.

PMID- 29035917
TI  - Decreases in smoking during treatment for methamphetamine-use disorders:
      preliminary evidence.
AB  - Despite high rates of smoking (70-90%) and the severely negative impact of
      smoking on physical and mental health, only 12% of individuals receiving
      stimulant-use disorder treatment also receive smoking-cessation treatment. The
      aim of this investigation was to examine the effect of a contingency management
      (CM) intervention targeting methamphetamine (MA) use on cigarette smoking. Sixty
      one adults with MA-use disorders who were smokers were assigned to CM or standard
      psychosocial treatment. Rates of smoking-negative breath samples (carbon monoxide
      <3 ppm) were compared between the two groups while controlling for baseline
      carbon monoxide level, marijuana use, MA use, and time. This subgroup of mostly
      male (59%) participants included 44 participants in the CM group and 17
      participants in the standard psychosocial treatment. Tobacco smoking participants
      who received CM targeting MA use were 140% (odds ratio: 2.395; 95% confidence
      interval: 1.073-5.346) more likely to submit a smoking-negative breath sample
      relative to standard psychosocial treatment during the treatment period, holding
      constant several other prespecified covariates. This study provides evidence that
      a behavioral treatment for MA use results in reductions in cigarette smoking in
      adults with MA-use disorder.

PMID- 29035920
TI  - The antidepressant-like effects of sinomenine in mice: a behavioral and
      neurobiological characterization.
AB  - Sinomenine is a bioactive alkaloid extracted from Sinomenium acutum. Here, we
      investigated the antidepressant effects of sinomenine in mice. The antidepressant
      actions of sinomenine were first examined in the forced-swim test and the tail
      suspension test, and then assessed in the chronic social defeat stress (CSDS)
      model of depression. Changes in the brain-derived neurotrophic factor (BDNF)
      signaling pathway after CSDS and sinomenine treatment were also investigated. A
      tryptophan hydroxylase inhibitor and a BDNF signaling inhibitor were also used to
      determine the pharmacological mechanisms of sinomenine. It was found that
      sinomenine induced antidepressant-like effects in the forced-swim test and tail
      suspension test without affecting the locomotor activity of mice. Sinomenine also
      prevented the CSDS-induced depressive-like symptoms. Moreover, sinomenine fully
      restored the CSDS-induced decrease in the hippocampal BDNF signaling pathway,
      whereas a BDNF signaling inhibitor, but not a tryptophan hydroxylase inhibitor,
      blocked the antidepressant effects of sinomenine. In conclusion, sinomenine
      exerts antidepressant effects in mice by promoting the hippocampal BDNF signaling
      pathway.

PMID- 29035919
TI  - Attenuation of compulsive-like behavior by fluvoxamine in a non-induced mouse
      model of obsessive-compulsive disorder.
AB  - The current study evaluated the role of strain and compulsive trait differences
      in response to fluvoxamine, a common obsessive-compulsive disorder (OCD) drug, in
      two different mouse strains (BIG1 and BIG2) with a spontaneous compulsive-like
      phenotype. For compulsive-like nest-building behavior, dose-dependent attenuation
      of nesting by fluvoxamine was observed for the BIG1 compulsive-like strain during
      the first hour after administration. No significant differences were found for
      the BIG2 strain during the first hour, although a dose-dependent trend similar to
      that in the BIG1 strain was observed. Fluvoxamine dose dependently decreased the
      number of marbles buried in both strains 1 h after administration. For anxiety
      like behaviors in the open field, no significant drug effects were found for the
      latency to leave the center and the number of line crossings. Significant strain
      differences were observed, with the BIG2 strain showing higher anxiety-like
      behaviors and reduced locomotor activity compared with the BIG1 strain.
      Consequently, this study adds predictive validity to our mouse model of OCD,
      whereas the anxiety-like differences between the strains add heterogeneity to our
      mouse model, similar to the heterogeneity observed in OCD.

PMID- 29035921
TI  - Biphasic effects of selective serotonin reuptake inhibitors on anxiety: rapid
      reversal of escitalopram's anxiogenic effects in the novelty-induced hypophagia
      test in mice?
AB  - In humans, chronic treatment with selective serotonin reuptake inhibitors (SSRIs)
      decreases anxiety, unlike acute treatment, which can increase anxiety. Although
      this biphasic pattern is observed clinically, preclinical demonstrations are
      rare. In an animal model of antidepressant-induced anxiolytic effects, the
      novelty-induced hypophagia (NIH) test, a single administration of the SSRI
      citalopram reportedly elicited anxiogenic-like effects, whereas three
      administrations over 24 h were sufficient to produce anxiolytic-like effects.
      Extending these findings, the present study examined the effects of acute and
      repeated escitalopram in a similar NIH test in a commonly used mouse strain (i.e.
      C57BL/6J), analyzing results with a method (i.e. survival analysis) that can
      model the skewed distribution of latencies to consume food and that can deal with
      censored data (i.e. when consumption does not occur during the test). Saline
      treated mice showed robust NIH. Acute escitalopram enhanced NIH, but did so only
      at a dose (i.e. 32 mg/kg) that similarly enhanced hypophagia in a familiar
      environment. The effects of escitalopram on NIH did not significantly change
      after repeated (three times) administration over 24 h. Additional studies are
      necessary to delineate the conditions under which rapid reversal of SSRI-induced
      anxiety can be modeled in animals using the NIH test.

PMID- 29035922
TI  - Effect of Scattering and Aberrations on Visual Acuity for Band Keratopathy.
AB  - SIGNIFICANCE: The progressive accumulation of the calcification may deteriorate
      corneal transparency, especially in the interpalpebral area, and subsequent
      visual performance for patients with band keratopathy. However, the detailed
      quantitative analysis of light scattering or higher-order aberrations on visual
      performance for these patients so far has not been elucidated. PURPOSE: The aim
      of this study was to assess the relationship of intraocular forward scattering,
      corneal backward scattering, and corneal higher-order aberrations with visual
      acuity in eyes with band keratopathy. METHODS: This prospective study comprised
      27 eyes of 27 consecutive patients who were diagnosed as having band keratopathy
      and age-matched 27 eyes of 27 healthy subjects. We quantitatively assessed
      objective scattering index using the double-pass instrument (Optical Quality
      Analysis System II; Visiometrics, Terrassa, Spain), corneal densitometry using
      the Scheimpflug rotating camera (Pentacam HR; Oculus, Wetzlar, Germany), and
      corneal higher-order aberrations using the Hartmann-Shack aberrometry (KR-9000;
      Topcon, Tokyo, Japan). RESULTS: The mean objective scattering index, corneal
      densitometry, corneal higher-order aberrations, and logarithm of the minimal
      angle of resolution (logMAR) visual acuity in eyes with band keratopathy were
      5.14 +/- 3.11, 36.42 +/- 10.55 gray-scale units, 0.33 +/- 0.10 MUm, and 0.03 +/-
      0.11 logMAR, respectively. These parameters were significantly larger in the band
      keratopathy group than in those in the control group (Mann-Whitney U test, P <
      .001). We found significant correlations of visual acuity with the objective
      scattering index (Spearman correlation coefficient, r = 0.465, P = .015), but no
      significant association with the corneal densitometry (r = 0.082, P = .683) or
      with corneal higher-order aberrations (r = -0.073, P = .718), in eyes having band
      keratopathy. CONCLUSIONS: Intraocular forward scattering, corneal backward
      scattering, and corneal higher-order aberrations in eyes with band keratopathy
      were significantly higher than those in normal eyes. Visual acuity was
      significantly correlated with intraocular forward scattering, but not with
      corneal backward scattering or corneal aberrations in the band keratopathy group,
      suggesting that intraocular forward scattering plays a vital role in visual
      performance in eyes with band keratopathy.

PMID- 29035923
TI  - Randomized Trial of Desktop Humidifier for Dry Eye Relief in Computer Users.
AB  - SIGNIFICANCE: Dry eye is a frequently reported problem among computer users. Low
      relative humidity environments are recognized to exacerbate signs and symptoms of
      dry eye, yet are common in offices of computer operators. Desktop USB-powered
      humidifiers are available commercially, but their efficacy for dry eye relief has
      not been established. PURPOSE: This study aims to evaluate the potential for a
      desktop USB-powered humidifier to improve tear-film parameters, ocular surface
      characteristics, and subjective comfort of computer users. METHODS: Forty-four
      computer users were enrolled in a prospective, masked, randomized crossover
      study. On separate days, participants were randomized to 1 hour of continuous
      computer use, with and without exposure to a desktop humidifier. Lipid-layer
      grade, noninvasive tear-film breakup time, and tear meniscus height were measured
      before and after computer use. Following the 1-hour period, participants reported
      whether ocular comfort was greater, equal, or lesser than that at baseline.
      RESULTS: The desktop humidifier effected a relative difference in humidity
      between the two environments of +5.4 +/- 5.0% (P < .001). Participants
      demonstrated no significant differences in lipid-layer grade and tear meniscus
      height between the two environments (all P > .05). However, a relative increase
      in the median noninvasive tear-film breakup time of +4.0 seconds was observed in
      the humidified environment (P < .001), which was associated with a higher
      proportion of subjects reporting greater comfort relative to baseline (36% vs.
      5%, P < .001). CONCLUSIONS: Even with a modest increase in relative humidity
      locally, the desktop humidifier shows potential to improve tear-film stability
      and subjective comfort during computer use.Trial registration no:
      ACTRN12617000326392.

PMID- 29035924
TI  - Rotational therapy in thoracic injuries: what is the evidence?
AB  - PURPOSE OF REVIEW: To review the current use of continuous lateral rotational
      therapy (CLRT) in patients with thoracic injuries and its impact on clinical
      course, complications and outcome. RECENT FINDINGS: Patient positioning is a key
      factor in the treatment of severe thoracic injuries and CLRT, and intermittent
      supine and prone position are basic options. There is a lack of randomized
      controlled studies for trauma patients with chest injury undergoing kinetic
      therapy as standard of care. A positive effect of kinetic therapy for prevention
      of secondary respiratory complications has been reported; nevertheless, no
      positive effect on mortality or length of hospital stay could be affirmed so far.
      In general, standardized therapeutic regimes for treatment of chest trauma have
      been implemented, including ventilator settings and positioning therapy. However,
      the available data do not allow a clear recommendation for rotational/kinetic
      therapy or prone positioning as superior or inferior. SUMMARY: The benefit of
      changing the patients' position for secret mobilization and recruitment of
      atelectasis after chest trauma and therefore preventing secondary complications
      seems to be self-evident. Since only few studies report about the utility of CLRT
      in critically ill chest trauma patients, randomized controlled multicenter trials
      are necessary to analyze the overall benefit of such means.

PMID- 29035925
TI  - Acute kidney injury in trauma patients.
AB  - PURPOSE OF REVIEW: To review epidemiology and pathophysiology of acute kidney
      injury (AKI) in trauma patients and propose strategies that aim at preventing AKI
      after trauma. RECENT FINDINGS: AKI in trauma patients has been reported to be as
      frequent as 50% with an association to a prolonged length of stay and a raise in
      mortality. Among the specific risk factors encountered in trauma patients,
      hemorrhagic shock, rhabdomyolysis severity, age, and comorbidities are
      independently associated with AKI occurrence. Resuscitation with balanced solutes
      seems to have beneficial effects on renal outcome compared with NaCl 0.9%,
      particularly in the context of rhabdomyolysis. However, randomized clinical
      studies are needed to confirm this signal. Abdominal compartment syndrome (ACS)
      is rare but has to be diagnosed to initiate a dedicated therapy. SUMMARY: The
      high incidence of AKI in trauma patients should lead to early identification of
      those at risk of AKI to establish a resuscitation strategy that aims at
      preventing AKI.

PMID- 29035926
TI  - Damage control surgery: current state and future directions.
AB  - PURPOSE OF REVIEW: Damage control surgery (DCS) represents a staged surgical
      approach to the treatment of critically injured trauma patients. Originally
      described in the context of hepatic trauma and postinjury-induced coagulopathy,
      the indications for DCS have expanded to the management of extra abdominal trauma
      and to the management of nontraumatic acute abdominal emergencies. Despite being
      an accepted treatment algorithm, DCS is based on a limited evidence with current
      concerns of the variability in practice indications, rates and adverse outcomes
      in poorly selected patient cohorts. RECENT FINDINGS: Recent efforts have
      attempted to synthesize evidence-based indication to guide clinical practice.
      Significant progress in trauma-based resuscitation techniques has led to improved
      outcomes in injured patients and a reduction in the requirement of DCS
      techniques. SUMMARY: DCS remains an important treatment strategy in the
      management of specific patient cohorts. Continued developments in early trauma
      care will likely result in a further decline in the required use of DCS in
      severely injured patients.

PMID- 29035927
TI  - The 2018 landscape of RA, PsA, and SpA pathogenesis.

PMID- 29035928
TI  - What did we learn from 'omics' studies in osteoarthritis.
AB  - PURPOSE OF REVIEW: 'Omics' technologies developed for the massive analysis of the
      major biologically relevant molecules (genes, proteins, metabolites) have been
      applied to the study of osteoarthritis (OA) for more than a decade. RECENT
      FINDINGS: 'Omics' studies have undoubtedly contributed to increase the knowledge
      on pathogenic processes related with OA and have provided hundreds to thousands
      of molecules that might have a putative biomarker utility for this disease.
      SUMMARY: This review describes the most recent 'omics' studies in OA research,
      their conclusions, and discuss those remaining challenges. Still many validation
      studies must be performed in large and well-characterized cohorts for the
      translation of the findings from 'omics' strategies to clinical applications. The
      development of tools for the intelligent integration of 'omics' data with
      clinical and imaging information is also mandatory to take full profit of the
      work that has been already performed.

PMID- 29035929
TI  - Vasculitis 2018: the bench and the bedside.

PMID- 29035930
TI  - Usefulness of PET in recognizing and managing vasculitides.
AB  - PURPOSE OF REVIEW: The aim of this article was to review the recent contributions
      to the scoring methods of PET in vasculitis as well as to its role in the
      diagnostic work-up. RECENT FINDINGS: Both visual and semiquantitative scoring
      methods can be used to interpret PET scans. PET has been shown to be both
      sensitive and specific in the diagnosis of large-vessel vasculitis. In addition,
      it also has a role in predicting vascular complications. SUMMARY: There is a need
      to better standardize the scoring methods used to interpret PET scans. In
      clinical practice, PET is useful to diagnose untreated individuals with suspected
      large-vessel vasculitis and contributes to identify patients at risk for vascular
      complications.

PMID- 29035931
TI  - Bioactive lipids in osteoarthritis: risk or benefit?
AB  - PURPOSE OF REVIEW: Lipids are bioactive molecules that can affect several
      biological functions. Technological developments allowing identification of novel
      lipid species and the study of their function have led to a significant advance
      in our understanding of lipid biology and their involvement in various diseases.
      This is particularly relevant for diseases associated with obesity in which lipid
      accumulation could be involved in pathogenesis. Here, we focus on osteoarthritis,
      a chronic joint disease aggravated by obesity, and will present the latest
      findings regarding the involvement of lipids in disease development and
      progression. RECENT FINDINGS: Recent studies indicate a possible involvement of n
      3 poly-unsaturated fatty acid and their anti-inflammatory and proresolving
      derivatives in osteoarthritis. These lipids were identified in the osteoarthritis
      joint, were found to have beneficial effects on cartilage in vitro and reduced
      pain in humans and animal models. Moreover, increased levels of cholesterol
      transport molecules, such as LDL particles, were recently associated with a
      higher risk of developing hand osteoarthritis in women and with more severe
      inflammation and osteophyte formation in osteoarthritis animal models. SUMMARY:
      Together, these findings indicate that lipids are a promising target for future
      therapeutic intervention in osteoarthritis and open exciting possibilities for
      future research.

PMID- 29035933
TI  - Psoriatic arthritis: new evidence for old concepts.
AB  - PURPOSE OF REVIEW: The review gives an updated overview of some of the new
      concepts in the management of psoriatic arthritis (PsA): early diagnosis,
      remission as an objective, treat-to-target, and treatment guidelines. RECENT
      FINDINGS: Early diagnosis, targeting remission as part of a treatment strategy,
      and new guidelines providing evidence-based support to these concepts are main
      topics in recent publications. SUMMARY: Dermatologists and rheumatologists should
      work together to reduce the number of patients remaining undiagnosed, and the
      time to do so.Remission definition in PsA is still controversial. There is good
      evidence and convincing arguments for both multidimensional measures, such as
      minimal disease activity, or unidimensional ones, as disease activity index for
      PsA. New data on the analysis of tight control of inflammation in early PsA trial
      showed that the strategy might not be cost-effective on the short term, and that
      oligoarthritis is less benefited.The new European League Against Rheumatism and
      Group for Research and Assessment of Psoriasis and PsA recommendations exhibit
      differences. Methotrexate and tumor necrosis factor inhibitors are favored in
      European League Against Rheumatism guidelines, whereas other conventional
      synthetic disease-modifying antirheumatic drugs and biologics are equally
      positioned in Group for Research and Assessment of Psoriasis and PsA
      recommendations.

PMID- 29035934
TI  - Dextrometorphan-Paroxetine, But Not Dronabinol, Effective for Treatment-Resistant
      Aggression and Agitation in an Elderly Patient With Lewy Body Dementia.

PMID- 29035932
TI  - Extracellular vesicles in cartilage homeostasis and osteoarthritis.
AB  - PURPOSE OF REVIEW: Extracellular vesicles carry bioactive molecules that can be
      transferred between cells and tissues. The purpose of this review is to describe
      how extracellular vesicles regulate functions of cells in cartilage and other
      joint tissues. The potential application of extracellular vesicles in the
      treatment of osteoarthritis and as biomarkers will also be discussed. RECENT
      FINDINGS: Extracellular vesicles are found in synovial fluid, in articular
      cartilage and in the supernatants of synoviocytes and chondrocytes. Extracellular
      vesicles in cartilage have been proposed to be involved in cross talk between
      cells in joint tissues and to affect extracellular matrix turnover and
      inflammation. Extracellular vesicles from arthritic joints can promote abnormal
      gene expression and changes in cartilage extracellular matrix, including abnormal
      mineralization. Promising results were obtained in the therapeutic application of
      mesenchymal stem cell-derived extracellular vesicles for cartilage repair and
      experimental osteoarthritis. SUMMARY: Extracellular vesicles have emerged as
      vehicles for the exchange of bioactive signaling molecules within cartilage and
      between joint tissues to promote joint homeostasis and arthritis pathogenesis. As
      the molecular content of extracellular vesicles can be customized, they offer
      utility in therapeutic applications.

PMID- 29035935
TI  - Prevalence and correlations between suicide attempt, depression, substance use,
      and functionality among patients with limb amputations.
AB  - Most patients undergoing limb amputations suffer significant emotional changes.
      The aim of this study was to estimate the prevalence of suicide attempts and
      depression in a sample of Mexican patients with limb amputations and, second, to
      determine whether the patients' functionality correlates with the presence of
      depression. We studied 40 patients who had undergone a limb amputation. The
      suicide attempt was evaluated using the Suicide Intent Scale. The depression was
      assessed using the Hamilton Depression Rating Scale, whereas the functionality of
      the patients was measured using the Functional Independence Measure. In this
      sample, 90% were men, whereas only 10% were women. In terms of the suicide
      behavior, we identified suicide attempts in 27.5% of the patients. The rate of
      depression was 92.5%. In the Functional Independence Measure, we observed that
      57.5% of the patients showed complete dependence. Finally, a significant
      correlation was found between depression and functionality (r=-0.75, P<0.001).
      The findings of the present study highlight the high incidence of suicide
      attempts and depression in Mexican patients with limb amputations. Also, we
      identified a correlation between the lack of functional independence and
      depression. Therefore, holistic interventions are necessary in these patients:
      rehabilitation therapy to increase their functionality, and psychological and
      pharmacology therapy to decrease suicidal behavior and depression. Finally, more
      studies using larger samples are necessary to obtain conclusive results.

PMID- 29035936
TI  - The Italian version of the Outpatient Physical Therapy Improvement in Movement
      Assessment Log: cross-cultural adaptation and psychometric properties.
AB  - Instruments to measure movement abilities from a patient's perspective are
      generally unavailable across diverse cultures and languages. The aim of this
      study was to translate, culturally adapt, and validate the Italian version of the
      Outpatient Physical Therapy Improvement in Movement Assessment Log (OPTIMAL)
      confidence scale. This study was an observational multicenter study. The Italian
      version of the OPTIMAL confidence scale (OPTIMAL-I) was developed following
      forward-backward translation and pretesting with a small group of patients.
      Reliability was measured by internal consistency (Cronbach alpha), and a factor
      analysis was carried out to explore the internal structure. Convergent validity
      was measured by comparing the OPTIMAL-I with the Italian version of the
      Activities-specific Balance Confidence (ABC-I). The process for obtaining the
      OPTIMAL-I required 3 months and it was administered to 290 outpatients in two
      different rehabilitation clinics. OPTIMAL-I showed high acceptability, high
      internal consistency (Cronbach's alpha=0.963), and high test-retest stability
      (intraclass correlation coefficient=0.92, P=0.001). Convergent validity with ABC
      I was also high (r=0.56-0.86; P<0.001). Using factor analysis, we found evidence
      for a four-factor structure related to 'confidence with high-loads lower
      extremity mobility', 'confidence with low-loads lower-extremity mobility',
      'confidence with upper-extremity mobility', and 'confidence with trunk mobility'
      that explained 78.83% of the total variance. The OPTIMAL-I showed good
      psychometric properties and its use can be recommended for measuring confidence
      in Italian patients receiving physical therapy services. Future studies should
      focus on divergent validity and construct validity.

PMID- 29035937
TI  - Ultrasound Detection of Arteria Comitans: A Novel Technique to Locate the Sciatic
      Nerve.
AB  - In the gluteal and thigh region, the arteria comitans accompanies the sciatic
      nerve for a short distance, then penetrates the nerve and runs to the lower part
      of the thigh. There is no study that recognizes this artery as a guide to the
      location of the sciatic nerve. In this report, we describe a series of 6 knee
      arthroplasty patients in whom ultrasound-guided sciatic nerve block was
      successfully performed using color Doppler and pulsed wave Doppler to visualize
      the arteria comitans as a guide to the location of the sciatic nerve. We have
      found that detecting the arteria comitans as a landmark is novel and may offer an
      additional tool with the existing methods for sciatic nerve block.

PMID- 29035938
TI  - Percutaneous excision of difficult osteoid osteomas using intraoperative AIRO CT
      navigation: a preliminary report.
AB  - Osteoid osteomas are well known for intraoperative technical difficulties for
      localization and adequate excision, especially when they are not clearly
      visualized on plain radiographs or when they occur in difficult and inaccessible
      situations. Localization in the radiology suite and shifting the patient to the
      operating room can be cumbersome, and can result in errors because of lack of
      real-time imaging. In these scenarios, intraoperative navigation will be useful.
      We report a technique of intraoperative computed tomography (CT) navigation for
      localization and excision of osteoid osteomas of the long bones. Six patients
      (four femoral and two tibial lesions) with a radiological diagnosis of osteoid
      osteoma, in whom the nidus could not be visualized clearly on plain radiographs,
      were treated with this technique. Intraoperative CT navigation with AIRO was
      performed and the images were registered to the computer. The lesion was then
      localized and excised using a high-speed burr. All patients underwent
      postexcision on-table CT scans, which showed complete excision of the nidus. All
      patients became symptom free and are doing well at a minimum follow-up of 6
      months. Intraoperative CT navigation helps to exactly localize the nidus and also
      helps to confirm complete excision of the nidus. This is a safe, effective and
      minimally invasive method to treat osteoid osteomas, particularly those that are
      not amenable to excision under C arm guidance.

PMID- 29035939
TI  - Predictors for the development of microalbuminuria and interaction with renal
      function.
AB  - AIM: It is important to know which factors predict the development of
      microalbuminuria in patients with diabetes mellitus type II. MATERIAL: Data from
      the Randomized Olmesartan and Diabetes Microalbuminuria Prevention Study were
      used to identify predictors for the new onset of microalbuminuria. Furthermore,
      the interaction of baseline albuminuria and baseline estimated glomerular
      filtration rate (eGFR) and the effects of treatment with olmesartan were
      investigated. RESULTS: A total of 4447 patients were randomized to receive 40-mg
      olmesartan or placebo for a median of 3.2 years. Baseline urinary albumin
      creatinine ratio (UACR) was the most important predictor of microalbuminuria,
      followed by age, weight, glycosylated hemoglobin type A1C, blood glucose, total
      cholesterol, SBP number of antihypertensive drugs and heart rate. The development
      of microalbuminuria was not affected by hemodynamic factors. The incidence of
      microalbuminuria increased from the lower to the higher UACR tertile at all
      baseline eGFR tertiles. The effects of olmesartan on prevention of new onset
      microalbuminuria were more obvious in those with the highest baseline UACR at all
      baseline eGFR tertiles. The eGFR declined more significantly in the olmesartan
      group (from 85.0 to 80.1 ml/min per 1.73 m), whereas the decrease in the placebo
      group was smaller (from 84.7 to 83.7 ml/min per 1.73 m). The highest rate of eGFR
      decline in the olmesartan group was in patients with the highest baseline eGFR
      (>95 ml/min per 1.73 m) at all baseline UACR tertiles. The transition from
      normoalbuminuria to microalbuminuria in the olmesartan treated patients was not
      accompanied by preservation of renal function. CONCLUSION: Predictors of new
      onset microalbuminuria are the classical cardiovascular risk factors.
      Microalbuminuria development was associated with baseline UACR but not baseline
      eGFR, whereas eGFR decrease after introduction of olmesartan was dependent on
      baseline eGFR but not on baseline UACR. The effects of olmesartan on
      microalbuminuria development and on eGFR decrease are probably mediated by
      different mechanisms.Clinical Trials.gov number, NCT00185159.

PMID- 29035940
TI  - Perspectives on hypertension's prevalence, treatment and control in a high
      cardiovascular risk East European country: data from the SEPHAR III survey.
AB  - OBJECTIVES: To estimate the trend in arterial hypertension's prevalence,
      awareness, treatment, and control in Romania, starting from the latest national
      survey Study for the Evaluation of Prevalence of Hypertension and Cardiovascular
      Risk in Romania III that has a crucial importance for the development of
      prevention strategies at national level. METHODS: A representative sample of 1970
      Romanian adults (mean age 48.38 years, age range 18-80 years, 52.5% women, 72.58%
      response rate), was enrolled. During the two study visits, three blood pressure
      (BP) measurements were performed at 1-min interval. Hypertension was defined as
      study SBP at least 140 mmHg and/or study DBP at least 90 mmHg at both study
      visits or previously diagnosed hypertension, regardless of BP values. BP control
      was defined as SBP less than 140 mmHg and DBP less than 90 mmHg in hypertensive
      patients. RESULTS: General hypertension prevalence is 45.1% (19.1% newly
      diagnosed hypertension, 80.9% awareness of hypertension), increasing with age,
      regardless of sex and area of residence. Although the majority (72.2%) of
      hypertensive patients were treated (51.9% with two or more drugs), only 30.8% of
      them had controlled BP values. Following the evolution from the last 11 years, it
      is expected that in 2020 the prevalence of hypertension to be up to 44%, the
      awareness up to 96.2%, treatment of hypertension up to 83.7%, and BP control up
      to 36.6%. CONCLUSION: Hypertension's prevalence in Romania is on the rise despite
      the increase in awareness, treatment, and control. Possible explanations of this
      trend might be the increasing incidence of unhealthy lifestyle and diet,
      including high salt intake, and a general increase in the prevalence of obesity,
      diabetes mellitus, and dyslipidemia.

PMID- 29035941
TI  - Arterial stiffness and cardiometabolic phenotype of Cameroonian Pygmies and
      Bantus.
AB  - BACKGROUND: Pygmies living in the Central African rainforest with a traditional
      hunter-gatherer lifestyle have a low incidence of cardiovascular diseases.
      Because of progressive loss of traditional habitat and ancestral lands, some
      Pygmies have migrated to urban areas and adopt specific Bantu lifestyles such as
      increased salt consumption and a sedentary way of life. We tested the hypothesis
      that migrant Pygmies could present with hemodynamic and metabolic characteristics
      different from those of traditional in-situ Pygmies and possibly closer to those
      of Bantu farmers. PATIENTS AND METHODS: The study included 148 Pygmies (94
      traditional and 54 migrants) and 164 Bantus. Peripheral and central hemodynamics,
      aortic pulse wave velocity (PWV), and augmentation index corrected for heart rate
      (AIx) were measured, as well as fasting lipid profile. Urinary sodium and
      potassium excretion was also measured on a morning spot. RESULTS: Compared to
      Bantus, Pygmies had lower height (even between men and women, but men were taller
      than women in the three groups), weight, waist and hip circumference, peripheral
      and central blood pressure, total, low-density lipoprotein, and high-density
      lipoprotein cholesterol and apolipoprotein B100 levels, sodium urinary excretion,
      and lower prevalence of the metabolic syndrome. By contrast, they had a higher
      waist-to-hip ratio, and higher triglycerides levels, as compared to Bantu
      farmers. PWV and AIx did not differ between Bantus and Pygmies. Compared to
      traditional in-situ Pygmies, migrant Pygmies were not taller when adjusted for
      sex, had lower brachial and central blood pressure, higher PWV (adjusted for mean
      arterial pressure, BMI, and sex), and higher apolipoprotein B100 levels. In the
      whole population, multivariable analysis revealed that PWV was independently
      associated with age, weight, height, mean arterial pressure, total cholesterol,
      and hip circumference, whereas AIx was independently related to age, sex, height,
      heart rate, diastolic blood pressure, and group (from Bantu farmers to Pygmies).
      CONCLUSION: Comparisons between Bantus and Pygmies, and between migrant Pygmies
      and traditional in-situ Pygmies, showed mixed results, with favorable and
      deleterious hemodynamic and metabolic characteristics in all groups. This could
      be due to increased contacts between these populations, which blunt the expected
      differences and because the beneficial effects of the hunter-gatherer subsistence
      mode of traditional in-situ Pygmies are counterbalanced by unhealthy behavioral
      habits.

PMID- 29035942
TI  - Phase II randomized sham-controlled study of renal denervation for individuals
      with uncontrolled hypertension - WAVE IV.
AB  - OBJECTIVES: The aim of this double-blind, randomized, sham-controlled study was
      to verify the blood pressure (BP)-lowering efficacy of externally delivered
      focused ultrasound for renal denervation (RDN). BACKGROUND: Nonrandomized, first
      proof-of-concept study and experimental evidence suggested that noninvasive
      techniques of RDN emerged as an alternative approach of RDN to invasive
      technologies. METHODS: WAVE IV, an international, randomized (1 : 1) sham
      controlled, double-blind prospective clinical study, was prematurely stopped.
      Patients were enrolled if office BP was at least 160 mmHg and 24-h ambulatory BP
      was at least 135 mmHg, while taking three or more antihypertensive medications.
      The treatment consisted of bilateral RDN using therapeutic levels of ultrasound
      energy and the sham consisted of bilateral application of diagnostic levels of
      ultrasound energy. RESULTS: In the 81 treated patients neither changes in office
      BP at 12 and 24 weeks, nor changes in 24-h ambulatory BP at 24-week follow-up
      visit differed between the two groups significantly. Of note, no safety signal
      was observed. Adherence analysis disclosed full adherence in 77% at baseline and
      82% at 6 months' follow-up visit. Post hoc analysis revealed that stricter
      criteria for stabilization of BP at baseline were associated with a numerically
      greater change in 24-h ambulatory BP in the RDN group than in the sham group.
      CONCLUSION: Our data did not prove that antihypertensive efficacy of the
      externally delivered focused ultrasound for RDN was greater than the sham effect.
      Stabilization of BP at baseline was identified as an important determinant of BP
      changes.

PMID- 29035943
TI  - Metabolic syndrome and subclinical carotid damage: a meta-analysis from
      population-based studies.
AB  - AIM: Metabolic syndrome (MetS) is a phenotype of growing prevalence in the
      general population. Information on the association between MetS and vascular
      damage in this setting is only based on data provided by single reports. We
      performed a meta-analysis of population-based studies aimed to assess the
      association of MetS with carotid atherosclerosis. DESIGN: Studies were identified
      by the following search terms: 'metabolic syndrome', 'general population,'
      'carotid intima-media thickness' (IMT), 'carotid atherosclerosis,' 'carotid
      damage,' 'ultrasonography.' The OVID-MEDLINE, PubMed, and the Cochrane Central
      Register of Controlled Trials databases were searched for English-language
      articles without time restriction up to 30 September 2016. RESULTS: Overall, 34
      635 study participants (22.9% with MetS) of both sexes were included in 21
      studies (sample size range 182-11 502). Mean common carotid IMT was higher in
      MetS study participants as compared with their non-MetS counterparts (759 +/- 41
      vs. 695 +/- 27 MUm), the standard means difference being 0.39 +/- 0.05
      (confidence interval: 0.29-0.48, P < 0.0001). This was also the case when pooled
      data were separately analysed according to sex. Differences in carotid IMT were
      unaffected by the presence of publication bias or single-study effect.
      CONCLUSION: Our findings support the view that MetS is a risk factor for early
      carotid atherosclerosis in members of the general population, regardless of sex.
      From a practical perspective, the ultrasound search of subclinical carotid
      disease may refine cardiovascular risk stratification and decision-making
      strategies in MetS individuals.

PMID- 29035944
TI  - Association between common carotid artery diameter and target organ damage in
      essential hypertension.
AB  - OBJECTIVES: To investigate the relationship between common carotid artery
      diameter (CCA-D) and target organ damage (TOD) in essential hypertension. METHODS
      AND RESULTS: A total of 200 essential hypertensive patients were enrolled (mean
      age 62.5 +/- 9.5, men 59.0%) and were classified into two groups by the height
      adjusted mean median of CCA-D: patients with CCA-D/height less than 3.905 mm/m (n
      = 100, 50%) and patients with CCA-D/height more than 3.905 mm/m (n = 100, 50%).
      Patients with CCA-D/height more than 3.905 mm/m have higher left ventricular mass
      index (LVMI) (P < 0.001) and higher prevalence of left ventricular hypertrophy
      (LVH) (P < 0.001), higher mean common carotid intima-media thickness (P = 0.008)
      and higher prevalence of carotid artery sclerosis (P = 0.03), higher pulse wave
      velocity (PWV) (P < 0.001) and higher prevalence of increased arterial stiffness
      (P = 0.01), higher urinary albumin/creatinine ratio (P = 0.001) and higher
      prevalence of microalbuminuria (P = 0.02) and greater number of TODs (P < 0.001)
      compared with the patients with CCA-D/height less than 3.905 mm/m. CCA-D was
      significantly correlated with LVMI, PWV and logarithmically transformed urinary
      albumin/creatinine ratio (r = 0.299, P < 0.001; r = 0.212, P = 0.007; r = 0.224,
      P = 0.005, respectively) after adjusting for cardiovascular risk factors.
      Multivariable stepwise linear regression analysis showed that number of TODs as
      well as individual TOD, including LVMI, PWV and logarithmically transformed
      urinary albumin/creatinine ratio, were independently correlated to height
      adjusted mean CCA-D (all P < 0.05). CONCLUSION: Height-adjusted mean CCA-D was an
      independent risk factor for individual TOD, including LVMI, PWV and urinary
      albumin/creatinine ratio, as well as overall number of TODs in essential
      hypertension.

PMID- 29035945
TI  - The functional consequences of the microbiome in HIV: insights from metabolomic
      studies.
AB  - PURPOSE OF REVIEW: It is critical to gain insight into the metabolic pathways by
      which the microbiota might influence HIV immunopathogenesis to exploit host
      microbiota interactions. The aim of this review is to sketch a very broad picture
      of recent advances in our knowledge of how HIV might affect the microbiota, with
      a focus on specific gene products, particularly, metabolites produced by the
      microbiota that may affect HIV immunopathogenesis. RECENT FINDINGS: First, we
      describe the different approaches used to explore imbalances in effector
      microbial products during HIV infection. Then, we review the mechanisms by which
      the microbiota might affect HIV immunopathogenesis. We cover several aspects of
      HIV immunopathogenesis, including systemic inflammation, mucosal immunity,
      enterocyte barrier integrity, HIV persistence and effects on HIV-specific humoral
      and cytotoxic responses. The altered interplay between mucosal immunity and
      dysbiotic bacteria helps to explain poorly understood observations in HIV
      infection, including susceptibility to HIV acquisition or the risk of HPV-related
      cancers, lung infections and cardiovascular disease. SUMMARY: Although there is
      an urgent need to standardize the methods used for assessing the functional level
      of the microbiota, it is recognized that functional modulation of the microbiota
      for therapeutic purposes should be evaluated to improve HIV care.

PMID- 29035946
TI  - Role of the lung microbiome in HIV pathogenesis.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize recent findings on
      the lung microbiome in HIV-infected patients and associated pulmonary diseases,
      and the relationship of airway microbial communities to metabolic and immune
      signatures within this patient population. RECENT FINDINGS: The lung microbiome
      in HIV infection is a relatively new and rapidly developing field; early studies
      in the field produced inconclusive evidence as to whether HIV-infection changes
      the lower airway microbiome. More recent microbiome investigations have addressed
      these inconsistencies by incorporating systems biology approaches and laboratory
      models. Several investigations have now identified enrichment of Prevotella,
      Veillonella, and Streptococcus in the lower airways as consistent correlates of
      advanced HIV-infection and HIV-associated pulmonary diseases. These bacteria are
      associated with specific metabolic and immune profiles within the lung and
      circulation, providing the first indication that the lung microbiome may play a
      functional role in the pathogenesis of HIV-infection and HIV-associated pulmonary
      disease. SUMMARY: This review summarizes knowledge to date on the lung microbiome
      in HIV infection, as well as challenges and accomplishments in the field within
      the last 2 years. Although the lung microbiome in HIV infection is still an
      emerging field, recent studies have formed a framework for future functional
      analysis of microbes in HIV pathogenesis.

PMID- 29035948
TI  - HIV and aging: role of the microbiome.
AB  - PURPOSE OF REVIEW: The purpose of this article is to review age-associated
      alterations in microbiota composition, diversity and functional features in
      context of immune senescence, chronic inflammation and comorbidities associated
      with HIV infection. The overall goal is to assess whether modulating the
      microbiome will likely improve resilience of the immune system and augment return
      to health. RECENT FINDINGS: Alteration in the gut microbiota composition
      diversity and function occur in HIV and aging. Importantly, butyrate producing
      bacteria are reduced in both HIV and aging individuals. There is increasing
      relevance of studying metabolomics in the context of HIV-associated non-AIDS
      comorbidities and aging. Interventional prospects of probiotics, prebiotics and
      fecal microbiota transplantation in HIV and aging will provide novel therapeutic
      approaches. SUMMARY: Increasing evidence suggests a significant link in changes
      in the composition, diversity and functional aspects of intestinal microbiome
      with normal aging and HIV infection. Data on association of metabolites produced
      by the microbiome with HIV-associated non-AIDS comorbidities is mounting. The
      impact of the microbiome alterations on inflammation, immune and organ senescence
      and mechanisms by which bio-behavioral pathways will exacerbate these outcomes
      needs to be further evaluated.

PMID- 29035949
TI  - The "iceberg" of reporting clinical trials.

PMID- 29035947
TI  - Cross-reactivity of HIV vaccine responses and the microbiome.
AB  - PURPOSE OF REVIEW: A successful human immunodeficiency virus-type 1 (HIV-1)
      vaccine will require immunogens that induce protective immune responses. However,
      recent studies suggest that the response to HIV-1 and perhaps other viruses may
      be altered by immune system exposure to intestinal microbiota-antigens. This
      review will discuss select aspects of these studies. RECENT FINDINGS: Naive CD4 T
      and B cell repertoires can be imprinted by intestinal microbiota-antigens to
      respond to virus epitopes prior to virus infection. A multiclade envelope (Env)
      gp145 DNA prime, recombinant adenovirus type 5 boost vaccine tested in a HIV
      Vaccine Trials Network (HVTN) phase IIb human vaccine efficacy trial (HVTN 505)
      induced a dominant gp41-reactive antibody response that was non-neutralizing and
      cross-reactive with intestinal microbiota. This vaccine regimen also induced a
      dominant gp41-reactive, intestinal microbiota-cross-reactive gp41 antibody
      response in neonatal and adult Rhesus macaques. Studies of naive CD4 T cells have
      demonstrated cross-reactivity to both HIV-1 and influenza peptides. SUMMARY: HIV
      1 Env vaccine-induced CD4 T and B cell responses can originate from a pool of
      intestinal microbiota-cross-reactive immune cells. Moreover, intestinal
      microbiota-cross-reactive HIV-1 Env antibodies are ineffective in protection
      against HIV-1 infection. Thus, intestinal microbiota-imprinting of the B cell
      repertoire may be one of several roadblocks to the induction of protective HIV-1
      antibodies.

PMID- 29035950
TI  - Nurse initiated protocols for spontaneous breathing trials in adult intensive
      care unit patients: a scoping review protocol.
AB  - REVIEW OBJECTIVES/QUESTIONS: The objectives of this scoping review are to explore
      the existing literature regarding protocols initated by nurses for a spontaneous
      breathing trial (SBT) in adult intensive care unit (ICU) patients, to examine and
      conceptually map the evidence, and to identify any gaps in the literature.The
      questions of this review are.

PMID- 29035951
TI  - Anthropometric prediction equations for estimating body mass composition: a
      scoping review protocol.
AB  - REVIEW QUESTIONS/OBJECTIVES: The overall aim of this scoping review is to
      determine the optimal anthropometric variable parameters used to develop
      predictive equation(s) to estimate the components of body mass composition.The
      objectives of the scoping review are:The questions for the scoping review are.

PMID- 29035952
TI  - The association between hip dysfunction and lower quarter injuries in long
      distance runners: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE:: The objective of this review is to establish the
      association between hip dysfunction and lower quarter (low back and lower limb)
      injuries in long distance runners. Specifically the review question is: Are long
      distance runners with hip dysfunction at risk of lower quarter (low back and
      lower limb) injuries?

PMID- 29035953
TI  - Rehabilitation for tibial plateau fractures in adults: a scoping review protocol.
AB  - REVIEW OBJECTIVE: Based on the observation that rehabilitation practices for
      tibial plateau fractures are inconsistent and lack uniformity in the published
      literature, this scoping review will seek to identify all relevant studies that
      have reported on rehabilitation for tibial plateau fractures in order to
      comprehensively map the characteristics of the practices. This scoping review
      will then be used to identify commonalities across the included studies in order
      to identify potential focus questions for subsequent systematic reviews.

PMID- 29035954
TI  - Effectiveness of dietary inorganic nitrate in lowering blood pressure in
      hypertensive adults: a systematic review protocol.
AB  - REVIEW QUESTION: The question of this review is: what is the effect of dietary
      inorganic nitrate on blood pressure in adults with blood pressure >120/80mmHg?

PMID- 29035955
TI  - Adolescents' decision to pursue bariatric surgery: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE:: The objective of this qualitative review is to
      identify what motivates an adolescent to pursue bariatric surgery.

PMID- 29035956
TI  - Information overload in consumers of health-related information: a scoping review
      protocol.
AB  - REVIEW QUESTION/OBJECTIVE:: The objective of this scoping review is to examine
      and map the breadth of evidence on information overload in lay adult and
      adolescent consumers of health-related information.

PMID- 29035957
TI  - Diagnostic test accuracy of self-reported frailty screening instruments in
      identifying community-dwelling older people at risk of frailty and pre-frailty: a
      systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE:: The question of this systematic review is: What is
      the diagnostic test accuracy of self-reported frailty screening instruments among
      community-dwelling older people against any of the following reference standard
      tests: the frailty phenotype, frailty index and comprehensive geriatric
      assessment?

PMID- 29035958
TI  - Forgiveness facilitation in palliative care: a scoping review protocol.
AB  - REVIEW QUESTION/OBJECTIVE:: The objective of this scoping review is to map the
      nature and extent of forgiveness facilitation interventions that have been
      implemented and evaluated in palliative care contexts. More specifically, the
      review questions are.

PMID- 29035959
TI  - Single room versus open-bay design in neonatal intensive care units for
      improvement in infant outcomes: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE:: The objective of this review is to identify the
      impact of single room neonatal intensive care unit (NICU) design on infant
      outcomes compared to alternative design.The specific question is: what is the
      impact of single room design on outcomes of infants cared for in intensive care
      units compared to those in alternative designs?

PMID- 29035960
TI  - Web-based therapeutic interventions for assessing, managing and treating health
      conditions in Indigenous people: a scoping review protocol.
AB  - REVIEW OBJECTIVES/QUESTIONS: The objective of the scoping review is to map the
      international scientific literature on web-based therapeutic interventions (WBTI)
      used by Indigenous people for assessing, managing and treating health conditions.
      The focus of this review is WBTIs for a broad range of health conditions,
      including but not limited to, communicable and non-communicable diseases, mental
      health conditions (including the broader concept of social and emotional
      wellbeing), use of harmful substances and gambling.The questions for the scoping
      review are.

PMID- 29035961
TI  - Behavioral and/or pharmacological interventions for managing sleep disturbances
      in children with autism spectrum disorder: an umbrella review protocol.
AB  - REVIEW QUESTION: What are effective behavioral interventions and/or
      pharmacological methods for managing sleep disturbances in children with autism
      spectrum disorder?

PMID- 29035962
TI  - Effectiveness of interstage home monitoring on healthcare outcomes in infants
      with hypoplastic left heart syndrome: a systematic review protocol.
AB  - REVIEW QUESTION: What is the effectiveness of home monitoring on interstage
      survival rates, weight gain, hospital admissions and cost savings in infants with
      hypoplastic left heart syndrome?

PMID- 29035963
TI  - Older hospitalized patients' experiences of dialogue with healthcare providers in
      hospitals: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE:: The objective is to identify and synthesize findings
      from qualitative studies of older (over 65 years) hospitalized patients'
      experiences of the barriers and facilitators to their dialogues with healthcare
      providers (HCPs) concerning their health and well-being.Specifically, the review
      questions are.

PMID- 29035964
TI  - Medication safety programs in primary care: a scoping review.
AB  - BACKGROUND: Medication safety plays an essential role in all healthcare
      organizations; improving this area is paramount to quality and safety of any
      wider healthcare program. While several medication safety programs in the
      hospital setting have been described and the associated impact on patient safety
      evaluated, no systematic reviews have described the impact of medication safety
      programs in the primary care setting. A preliminary search of the literature
      demonstrated that no systematic reviews, meta-analysis or scoping reviews have
      reported on medication safety programs in primary care; instead they have focused
      on specific interventions such as medication reconciliation or computerized
      physician order entry. This scoping review sought to map the current medication
      safety programs used in primary care. OBJECTIVE: The current scoping review
      sought to examine the characteristics of medication safety programs in the
      primary care setting and to map evidence on the outcome measures used to assess
      the effectiveness of medication safety programs in improving patient safety.
      INCLUSION CRITERIA TYPES OF PARTICIPANTS: The current review considered
      participants of any age and any condition using care obtained from any primary
      care services. CONCEPT: We considered studies that focussed on the
      characteristics of medication safety programs and the outcome measures used to
      measure the effectiveness of these programs on patient safety in the primary care
      setting. CONTEXT: The context of this review was primary care settings, primary
      healthcare organizations, general practitioner clinics, outpatient clinics and
      any other clinics that do not classify patients as inpatients. TYPES OF STUDIES:
      We considered all quantitative studied published in English. SEARCH STRATEGY: A
      three-step search strategy was utilized in this review. DATA EXTRACTION: Data
      were extracted from the included studies to address the review question. The data
      extracted included type of medication safety program, author, country of origin,
      aims and purpose of the study, study population, method, comparator, context,
      main findings and outcome measures. RESULTS: The objectives, inclusion criteria
      and methods for this scoping review were specified in advance and documented in a
      protocol that was previously published. This scoping review included nine studies
      published over an eight-year period that investigated or described the effects of
      medication safety programs in primary care settings. We classified each of the
      nine included studies into three main sections according to whether they included
      an organizational, professional or patient component. The organizational
      component is aimed at changing the structure of the organization to implement the
      intervention, the professional component is aimed at the healthcare professionals
      involved in implementing the interventions, and the patient component is aimed at
      counseling and education of the patient. All of the included studies had
      different types of medication safety programs. The programs ranged from complex
      interventions including pharmacists and teams of healthcare professionals to
      educational packages for patients and computerized system interventions. The
      outcome measures described in the included studies were medication error
      incidence, adverse events and number of drug-related problems. CONCLUSION: Multi
      faceted medication safety programs are likely to vary in characteristics. They
      include educational training, quality improvement tools, informatics, patient
      education and feedback provision. The most likely outcome measure for these
      programs is the incidence of medication errors and reported adverse events or
      drug-related problems.

PMID- 29035965
TI  - Effectiveness of bedrails in preventing falls among hospitalized older adults: a
      systematic review.
AB  - BACKGROUND: Falls are a major problem today affecting adults of any age, but the
      elderly are a population that is more susceptible to falls. Falls are the leading
      cause of injury or death among older adults. Hospitalized older people are
      particularly vulnerable to falls. Falls cause direct injuries (minor injuries,
      severe wounds of the soft tissues and bone fractures) to patients and increased
      length of stay. The prevention of falls is commonly considered an indicator of
      the quality of care. Therefore, health institutions and professionals treat the
      identification and implementation of strategies to prevent or minimize their
      effects as a high priority. Fall prevention interventions involving physical
      restraints are still common and considered a primary preventative measure,
      despite controversy in their use. One of the most frequently used restraint
      interventions is bedrails. The question of the effectiveness of bedrails in
      preventing falls cuts across all societies and cultures and has with significant
      implications for the clinical practice of nurses. OBJECTIVES: The objective of
      this review was to identify the effectiveness of the use of bedrails in
      preventing falls among hospitalized older adults when compared with no use of
      bedrails or any type of physical restraints. INCLUSION CRITERIA TYPES OF
      PARTICIPANTS: The current review considered studies that included hospitalized
      adults (female and male), 65 years and over with any clinical condition in a non
      intensive care unit (ICU). TYPES OF INTERVENTION(S): The current review
      considered studies that evaluated the use of bedrails as a restraint to prevent
      falls among older adults in non-ICUs compared to no use of bedrails or any type
      of physical restraints, for example, bedrails versus no bedrails, and bedrails
      versus no wrist or ankle ties. TYPES OF STUDIES: The current review considered
      any randomized controlled trials (RCTs). In the absence of RCTs, other research
      designs such as non-RCTs, before and after studies, cohort studies, case-control
      studies, descriptive studies, case series/reports and expert-opinion were
      considered. OUTCOMES: The current review considered studies that included primary
      outcomes (number of patients who fell or the number of falls per patient) and
      secondary outcomes (number of head trauma, bone fractures or soft tissue
      injuries). SEARCH STRATEGY: The search strategy aimed to find both published and
      unpublished articles. A three-step search strategy was utilized in 13 databases.
      Articles published in Portuguese, English and Spanish beginning from 1980 were
      considered for inclusion. METHODOLOGICAL QUALITY: Assessment of methodological
      quality was not conducted as no articles were identified that met the inclusion
      criteria. DATA EXTRACTION AND DATA SYNTHESIS: Data extraction and synthesis was
      not performed, because no articles were included in this systematic review.
      RESULTS: The search identified a total of 875 potentially relevant articles.
      Sixteen articles were identified through the reference lists of all identified
      articles. One hundred and thirteen full-text papers were assessed by two
      independent reviewers to determine eligibility. However, 11 articles were not
      found (despite all the efforts), and 102 articles did not meet the inclusion
      criteria. CONCLUSION: There is no scientific evidence comparing the use of
      bedrails in preventing falls among hospitalized older adults to no use of
      bedrails or any type of physical restraints.

PMID- 29035966
TI  - Effectiveness of rifampicin chemoprophylaxis in preventing leprosy in patient
      contacts: a systematic review of quantitative and qualitative evidence.
AB  - BACKGROUND: Individuals in contact with patients who have leprosy have an
      increased risk of disease exposure, which reinforces the need for
      chemoprophylactic measures, such as the use of rifampicin. OBJECTIVES: The
      objective of the review was to synthesize the best available evidence regarding
      the effectiveness of rifampicin chemoprophylaxis for contacts with patients with
      leprosy, and to synthesize the best available evidence on the experience and
      acceptability of rifampicin chemoprophylaxis as reported by the contacts and
      health professionals involved in the treatment of leprosy or Hansen's disease.
      INCLUSION CRITERIA TYPES OF PARTICIPANTS: In the quantitative component,
      individuals in contact with leprosy patients were included. In the qualitative
      component, in addition to contacts, health professionals who were in the practice
      of treating leprosy were included. TYPES OF INTERVENTION(S)/PHENOMENA OF
      INTEREST: The quantitative component considered as an intervention rifampicin at
      any dose, frequency and mode of administration, and rifampicin combination
      regimens.The qualitative component considered as phenomena of interest the
      experience and acceptability of rifampicin chemoprophylaxis. TYPES OF STUDIES:
      The quantitative component considered experimental and observational studies
      whereas the qualitative component considered studies that focused on qualitative
      data, including but not limited to, designs such as phenomenology, grounded
      theory, ethnography and action-research. OUTCOMES: The quantitative component
      considered studies that reported on outcomes such as the development of clinical
      leprosy in the contacts of patients who had leprosy, incidence rates, adverse
      effects and safety/harmful effects of the intervention. SEARCH STRATEGY: A three
      step strategy for published and unpublished literature was used. The search for
      published studies included: PubMed, Cumulative Index to Nursing and Allied Health
      Literature, Cochrane Library, Scopus, Web of Science, National Institute for
      Health and Clinical Excellence, Latin American and Caribbean Health Sciences
      Literature; and Google Scholar and EVIPnet for unpublished studies. Studies
      published from the time of the respective database inception to January 2016 in
      English, Spanish, Portuguese, Japanese and Chinese were considered.
      METHODOLOGICAL QUALITY: Two reviewers independently assessed the studies for
      methodological quality using standardized critical appraisal instruments from the
      Joanna Briggs Institute. DATA EXTRACTION: Standardized data extraction tools
      developed by the Joanna Briggs Institute were used to extract quantitative and
      qualitative data from papers included in the review. DATA SYNTHESIS: Due to
      clinical and methodological heterogeneity in the interventions of the included
      studies, no statistical meta-analysis was possible. Quantitative and qualitative
      research findings are presented in narrative form. RESULTS: Following critical
      appraisal, eight studies were included in this review, seven quantitative and one
      qualitative. The reduction in incidence of leprosy, using one dose of rifampicin
      in the first two years, was 56.5%; in the follow up period of one to four years,
      the reduction was 34.9%. The combination of rifampicin and the Bacillus Calmette
      Guerin vaccine showed a preventative effect of 80% against the disease. The only
      controlled clinical trial using two doses of rifampicin was community-based and
      did not indicate effectiveness of the intervention. The qualitative findings
      showed social acceptability of rifampicin. CONCLUSIONS: Chemoprophylaxis with one
      dose of rifampicin is found to be effective in preventing contacts of leprosy
      patients from contracting the disease. Also, there is indication that this
      strategy is socially accepted.

PMID- 29035967
TI  - Pediatric clinical handover: a best practice implementation project.
AB  - BACKGROUND: Communication of information between and among healthcare providers
      is an essential element of patient care. Poor clinical handover has been
      associated with inaccurate clinical assessment and diagnosis, delays in
      diagnosis, medication errors and decreased patient satisfaction. Effective and
      efficient transition of patient care information requires an evidence-based
      handover approach. OBJECTIVES: The aim of this evidence implementation project
      was to make a contribution to promote evidence-based practice in clinical
      handover in a pediatric setting and thereby enhance patient safety and service
      delivery. METHODS: Seven criteria identified by the Joanna Briggs Institute were
      used to conduct an audit in the Gastroenterology Department, Children's Hospital
      of Fudan University, Shanghai, People's Republic of China. Twelve nurses and 260
      handover sessions were involved. The JBI Practical Application of Clinical
      Evidence System and Getting Research into Practice audit tools for promoting
      change in health practice were used to ascertain compliance with the criteria
      before and after the implementation of best practice. The program included three
      phases and was conducted over six months. RESULTS: There were improvements with
      compliance for each criterion. Face-to-face communication, standardized
      documentation, identification of patients, care plan handover and transfer of
      responsibility reached 100% compliance. Detailed observations of the patient
      improved from 93% to 98%, and there was an 18% improvement for relevant history
      handover. CONCLUSIONS: This project has demonstrated that handover sessions can
      be more effective by translating evidence into practice through ongoing evidence
      based audit. Nursing inter-shift handover requires the use of a highly valuable
      and important standardized tool. Further audits will need to be carried out in
      order to maintain the practice change, and ensure the sustainability of the
      project.

PMID- 29035968
TI  - The final word on nutritional screening and assessment in older persons.
AB  - PURPOSE OF REVIEW: To provide an updated perspective of how nutritional screening
      and assessment in older persons should be performed and reasonably implemented in
      the near future. RECENT FINDINGS: Although nutritional screening and assessment
      should be fast and easy procedures, there is increasing evidence that more time
      should be dedicated to them. This is probably an answer to the claim to a
      medicine being more preventive than curative. Increasing interest is currently
      given to healthy aging and nutritional status is more likely to be addressed for
      its implications on functional status and disability. Important prognostic
      conditions, such as frailty, sarcopenia, and cachexia, which are closely linked
      to the nutritional domain, are at the top of the agenda. Therefore, body
      composition is a key issue and functional status is suggested as primary endpoint
      of nutrition trials. In this scenario, there is also a rationale for systematic
      assessment of inflammation, protein intake, and vitamin D status as potential
      contributing factors to reduced muscle mass and function. SUMMARY: A 'second
      generation' multidimensional nutritional screening and assessment including the
      evaluation of body composition, frailty, sarcopenia, and cachexia could be
      hypothesized. Nutritional assessment should be also completed by the systematic
      evaluation of inflammation, protein intake, and vitamin D status.

PMID- 29035970
TI  - Emerging perspectives on branched-chain amino acid metabolism during adipocyte
      differentiation.
AB  - PURPOSE OF REVIEW: Adipogenesis has been extensively studied in the context of
      carbohydrate and lipid metabolism. However, little information exists on the role
      of amino acid metabolism during adipocyte differentiation. Here, we review how
      branched-chain amino acid (BCAA) metabolism is modified during adipogenesis and,
      due to the limited information in the area, address questions that remain to be
      answered with further research. RECENT FINDINGS: BCAAs are rapidly consumed
      during adipocyte differentiation and are indispensable for this process.
      Furthermore, we describe how BCAA catabolic enzymes and the metabolic fate of
      BCAAs are modified during adipogenesis. SUMMARY: Obesity is a chronic disease
      characterized by increased adipose tissue due to either an increase in the size
      (hypertrophy) and/or number of adipocytes (hyperplasia). Hyperplasia is
      determined by the rate of adipogenesis. Therefore, understanding the mechanism
      that modulates adipogenesis in the context of amino acid metabolism will help to
      establish pharmacological and dietary interventions involving the type and amount
      of dietary protein for the treatment of obesity and its associated
      comorbidities.Video abstract http://links.lww.com/COCN/A11.

PMID- 29035971
TI  - Dietary patterns and cognition in older persons.
AB  - PURPOSE OF REVIEW: The current article reviews recently published evidence of the
      important role that specific dietary patterns may hold on preventing cognitive
      impairment and dementia over aging. RECENT FINDINGS: Specific dietary patterns
      attributed to targeting cardiovascular risk factors may protect against the
      development of mild cognitive impairment (MCI) and dementia, especially
      Alzheimer's disease. Numerous epidemiological studies have strongly suggested
      that multinutrient approaches using the Mediterranean diet (Med diet), dietary
      approach to systolic hypertension (DASH) and the Mediterranean-DASH diet
      intervention for neurodegenerative delay (MIND) are associated with a lower risk
      of cognitive impairment, MCI and Alzheimer's disease in older persons. This
      multinutrient approach seems to hold better outcomes than single nutrient
      intervention. There is only one randomized clinical trial (PREDIMED study)
      showing an improvement in cognitive performance over time in those undergoing a
      Med diet protocol. SUMMARY: Nutrition is an essential and modifiable risk factor
      that plays a role on preventing and/or delaying the onset of dementia. There is
      sufficient evidence to hypothesize testing neuroprotective dietary patterns on
      cognition in randomized clinical trials in older persons. Healthy dietary
      patterns such as the Med diet, DASH and MIND deserve further attention in
      randomized clinical trials on cognitive performance outcomes.

PMID- 29035969
TI  - Effects of medical food leucine content in the management of methylmalonic and
      propionic acidemias.
AB  - PURPOSE OF REVIEW: The current review highlights the varied effects of medical
      foods high in leucine (Leu) and devoid of valine (Val) and isoleucine (Ile) in
      the management of methylmalonic acidemia (MMA) and propionic acidemia and
      cobalamin C (cblC) deficiency, aiming to advance dietary practices. RECENT
      FINDINGS: Leu is a key metabolic regulator with a multitude of effects on
      different organ systems. Recent observational studies have demonstrated that
      these effects can have unintended consequences in patients with MMA as a result
      of liberal use of medical foods. The combination of protein restriction and
      medical food use in MMA and propionic acidemia results in an imbalanced branched
      chain amino acid (BCAA) dietary content with a high Leu-to-Val and/or Ile ratio.
      This leads to decreased plasma levels of Val and Ile and predicts impaired brain
      uptake of multiple essential amino acids. Decreased transport of methionine (Met)
      across the blood-brain barrier due to high circulating Leu levels is of
      particular concern in cblC deficiency in which endogenous Met synthesis is
      impaired. SUMMARY: Investigations into the optimal composition of medical foods
      for MMA and propionic acidemia, and potential scenarios in which Leu
      supplementation may be beneficial are needed. Until then, MMA/propionic acidemia
      medical foods should be used judiciously in the dietary management of these
      patients and avoided altogether in cblC deficiency.

PMID- 29035973
TI  - The relevance of dietary protein after bariatric surgery: what do we know?
AB  - PURPOSE OF REVIEW: The growing obesity epidemic is associated with an increased
      demand for bariatric surgery with Roux-en-Y Gastric Bypass and Sleeve Gastrectomy
      as the most widely performed procedures. Despite beneficial consequences,
      nutritional complications may arise because of anatomical and physiological
      changes of the gastrointestinal tract. The purpose of this review is to provide
      an update of the recent additions to our understanding of the impact of bariatric
      surgery on the intake, digestion and absorption of dietary protein. RECENT
      FINDINGS: After bariatric surgery, protein intake is compromised because of
      reduced gastric capacity and aversion for certain foods. A minority of patients
      reaches the recommended protein intake of minimal 60 g per day, which results in
      the loss of fat-free mass rather than the desired loss of fat mass. Despite
      inadequate protein intake, protein digestion and absorption do not seem to be
      impaired suggesting that other mechanisms could counteract the reduced secretion
      of digestive enzymes and their delayed inlet. SUMMARY: After bariatric surgery,
      protein supplementation or diet enrichment could attribute to achieve the minimal
      recommended protein intake and benefit the amount and composition of
      postoperative weight loss.

PMID- 29035972
TI  - Hyperammonemia and proteostasis in cirrhosis.
AB  - PURPOSE OF REVIEW: Skeletal muscle loss or sarcopenia is a frequent complication
      of cirrhosis that adversely affects clinical outcomes. As skeletal muscle is the
      largest store of proteins in the body, proteostasis or protein homeostasis is
      required for maintenance of muscle mass. This review will focus on disordered
      skeletal muscle proteostasis in liver disease. RECENT FINDINGS: Increased
      skeletal muscle uptake of ammonia initiates responses that result in disordered
      proteostasis including impaired protein synthesis and increased autophagy. The
      cellular response to the stress of hyperammonemia (hyperammonemic stress
      response, HASR) involves the coordinated action of diverse signaling pathways
      targeting the molecular mechanisms of regulation of protein synthesis.
      Transcriptional upregulation of myostatin, a TGFbeta superfamily member, results
      in impaired mTORC1 signaling. Phosphorylation of the eukaryotic translation
      initiation factor 2alpha (eIF2alpha) also relates to decreased global protein
      synthesis rates and mTORC1 signaling. Ammonia also causes mitochondrial and
      bioenergetic dysfunction because of cataplerosis of alpha-ketoglutarate. Lowering
      ammonia, targeting components of HASR and regulating cellular amino acid levels
      can potentially restore proteostasis. SUMMARY: Signaling via myostatin and
      eIF2alpha phosphorylation causes decreases in protein synthesis and mTORC1
      activity with a parallel mitochondrial dysfunction and increased autophagy
      contributing to proteostasis perturbations during skeletal muscle hyperammonemia
      of liver disease.

PMID- 29035975
TI  - Breath Hydrogen Testing in East and Southeast Asia.
AB  - Breath hydrogen tests are popular, noninvasive tests for the assessment of
      carbohydrate fermentation in patients with irritable bowel syndrome (IBS) and
      functional dyspepsia (FD). There is limited information regarding the utility of
      breath hydrogen and methane tests in IBS and FD patients in East and Southeast
      Asia. This review aims to summarize current literature about common indications
      of breath testing in this region, the genesis of functional gastrointestinal
      symptoms by provocative breath testing and provide suggestions for correct use.
      The most common testing indication is the assessment of lactose intolerance,
      followed by small intestinal bacterial overgrowth (SIBO) and differentiation of
      intestinal gas profiles in research setting. Studies in this region not only
      documented a high prevalence of lactose malabsorption but a population, both
      healthy and IBS, that is highly symptomatic to typical lactose intakes. Breath
      hydrogen assessment of other fermentable carbohydrates (FODMAPs) are fairly
      uncommon, whereas methane breath testing is almost nonexistent. Cumulative
      hydrogen production following lactulose was also not excessive in IBS patients
      compared with controls. The evidence however, for the detection of SIBO suggests
      limited reliability in the use of lactulose or glucose breath testing alone and
      inconclusive data on its correlation with symptoms. Conversely, little has been
      carried out in FD. In conclusion, breath testing should be limited in the
      predicting patients with SIBO for directing clinical management but can be
      considered in the objective assessment of lactose malabsorption within a low
      FODMAP diet. Recommendations to improve the interpretation of breath testing in
      research were also provided.

PMID- 29035974
TI  - Altered ultrasonic vocalization in neonatal SAPAP3-deficient mice.
AB  - Ultrasonic vocalizations (USVs) in neonatal mice provide a means of modeling
      communication deficits in neurodevelopmental disorders. Mature mice deficient in
      SAP90/PSD95-associated protein 3 (SAPAP3) display compulsive grooming and anxiety
      like behavior, conditions that are often associated with neurodevelopmental
      disorders. To date, however, aspects of neurodevelopment have not been
      investigated in SAPAP3-deficient mice. Here, we examined whether neonatal SAPAP3
      deficient mice display altered USVs. We recorded USVs from 5-day-old sapap3 and
      sapap3 mice, and also monitored developmental reflexes in these mice during the
      early postnatal period. Sapap3 mice display an increase in the number and
      duration of USV calls relative to sapap3 littermates, despite otherwise similar
      developmental profiles. Thus, SAPAP3, previously well-characterized for its role
      in compulsive grooming, also plays a heretofore unidentified role in neonatal
      communication. Aberrant social communication and compulsive behavior are core
      symptoms of autism spectrum disorders, and these results show that SAPAP3
      deficient mice may serve to model some aspects of these conditions.

PMID- 29035976
TI  - The Impact of Obesity on Mortality and Other Outcomes in Patients With
      Nonvariceal Upper Gastrointestinal Hemorrhage in the United States.
AB  - GOALS: To quantify in patients with nonvariceal upper gastrointestinal hemorrhage
      (NVUGIH) the relationship between obesity and mortality, disease severity,
      treatment modalities, and resource utilization. BACKGROUND: NVUGIH is the most
      common gastrointestinal emergency. STUDY: Adults with a principal diagnosis of
      NVUGIH were selected from the 2014 National Inpatient Sample. The primary outcome
      was in-hospital mortality. Secondary outcomes were hemorrhagic shock, prolonged
      mechanical ventilation (PMV), upper endoscopy [esophagogastroduodenoscopy (EGD)],
      radiologic treatment, surgery, length of hospital stay (LOS), and total
      hospitalization costs and charges. Confounders were adjusted for using
      multivariable regression analyses. RESULTS: In total, 227,480 admissions with
      NVUGIH were included, 11.70% of whom were obese. Obese and nonobese patients had
      similar odds of mortality (aOR: 0.88; 95% confidence interval [CI]: 0.69-1.12;
      P=0.30), EGD within 24 hours of admission (aOR: 0.95; CI: 0.89-1.01; P=0.10),
      radiologic treatment (aOR: 1.06; CI: 0.82-1.35; P=0.66), and surgery (aOR: 1.27;
      CI: 0.94-1.70; P=0.11). However, obese patients had higher odds of shock (aOR:
      1.30; CI: 1.14-1.49; P<0.01), PMV (aOR: 1.39; CI: 1.18-1.62; P<0.01), undergoing
      an EGD (aOR: 1.27; CI: 1.16-1.40; P<0.01), needing endoscopic therapy (aOR: 1.18;
      CI: 1.09-1.27; P<0.01), a longer LOS (0.31 d; CI: 0.16-0.46 d; P<0.01), higher
      costs ($1075; CI: $636-$1514; P<0.01), and higher charges ($4084; CI: $2060
      $6110; P<0.01) compared with nonobese patients. CONCLUSIONS: Obesity is not an
      independent predictor of NVUGIH mortality. However, obesity is associated with a
      more severe disease course (shock and PMV), higher rates of EGD and endoscopic
      therapy use, and significant increases in resource utilization (hospital LOS,
      total hospitalization costs, and charges).

PMID- 29035977
TI  - Long-Term Safety of Using Local Anesthetic Injections in Professional Rugby
      League for Modified Indications.
AB  - OBJECTIVE: To assess and evaluate the long-term safety of local anesthetic
      injections before or during games in professional rugby league players. DESIGN:
      Retrospective case series. SETTING: Professional rugby league team. PARTICIPANTS:
      Sydney Roosters players over a 6-year period (2008-2013), who had been
      administered a local anesthetic injection for an injury before or during a match
      to aid return to play. INTERVENTIONS: Follow-up survey (no active intervention).
      MAIN OUTCOME MEASURES: Player self-reported satisfaction. Survey results were
      compared with a previous cohort who had received local anesthetic injection from
      1998 to 2007. RESULTS: Thirty-two players who had been injected with local
      anesthetic on 249 occasions for 81 injuries completed the current survey at an
      average of 5.64 years postinjection. In the cohort of 2008 to 2013, fewer
      injections were performed to areas deemed higher risk compared with the 1998 to
      2007 cohort (P < 0.00002). The vast majority of players (80/81 cases) would
      repeat the injection in the same circumstances and reported that ongoing side
      effects were uncommon. There were 6 cases (8%) in which players reported
      significant ongoing pain in the area of injection at long-term follow-up.
      CONCLUSIONS: This study affirmed the long-term safety of injections in most
      cases. LEVEL OF EVIDENCE: IV.

PMID- 29035978
TI  - Use of Blood Biomarkers in the Assessment of Sports-Related Concussion-A
      Systematic Review in the Context of Their Biological Significance.
AB  - OBJECTIVES: To critically review current knowledge on the positive and negative
      predictive value of blood biomarkers for concussion; to illustrate the clinical
      and biological contexts that help evaluate the use of these markers in sport
      related traumatic brain injuries (TBIs). METHODS: This systematic review was
      performed in accordance with PRISMA guidelines. We reviewed the measurement,
      clinical utility, endpoint, and biological significance of blood biomarkers in
      concussion. RESULTS: A total of 4352 publications were identified. Twenty-six
      articles relating to blood biomarkers were included in the review. Four common
      blood biomarkers, namely S100B, tau, neuron-specific enolase (NSE), and glial
      fibrillary acidic protein (GFAP), were examined. Overall, the studies showed
      S100B measurement and use, either acutely or at several time points, can
      distinguish injured from noninjured patients with an uncertain degree of utility
      in predicting mortality. At present, S100B has largely become an acceptable
      biomarker of TBI; however, studies have begun to highlight the need to
      incorporate clinical symptoms instead of S100B concentration in isolation on the
      basis of inconsistent results and lack of specificity across published studies.
      Further research is needed to evaluate and validate the use of tau, NSE, and GFAP
      as a diagnostic aid in the management of concussion and TBI. CONCLUSIONS: At
      present, blood biomarkers have only a limited role in the evaluation and
      management of concussion. Although several biomarkers of brain injury have been
      identified, continued research is required. S100B holds promise as the most
      clinically useful diagnostic biomarker. Blood biomarkers, in combination with
      other clinical data, such as head computed tomography, would maximize the
      diagnostic accuracy. The methodological limitations evident in blood biomarker
      research results in the need for the clinical utility of blood biomarker use in
      concussion to be further explored.

PMID- 29035979
TI  - Effect of a Commercially Available Footwear Insole on Biomechanical Variables
      Associated With Common Running Injuries.
AB  - OBJECTIVE: To determine whether Dr. Scholl's Active Series (DSAS) footwear
      insoles alter biomechanical variables associated with running injuries. DESIGN:
      Randomized, controlled experiment. SETTING: Sport medicine and biomechanics gait
      analysis laboratory. PARTICIPANTS: Fifteen healthy adults. INTERVENTIONS: The
      control condition was the participant's own athletic footwear. The experimental
      condition was the participant's own athletic footwear plus a DSAS insole.
      Participants completed running gait analysis trials with each condition. MAIN
      OUTCOME MEASURES: Peak vertical loading rates (VLRs), peak ankle eversion
      velocities (AEVs), peak ankle eversion angles (AEAs), and knee abduction angular
      impulses (KAAIs) were calculated and compared between the control and DSAS
      conditions because these variables have been associated with plantar fasciitis
      (VLRs), tibial stress syndrome (AEVs, AEAs), and patellofemoral pain syndrome
      (KAAIs). RESULTS: Dr. Scholl's Active Series insoles reduced VLRs across
      participants by 16% (P < 0.001) but had no consistent influence on AEVs, AEAs, or
      KAAIs. Participant-specific responses showed that most runners either experienced
      AEA and KAAI reductions or no change with the DSAS insole, whereas AEVs commonly
      increased with the DSAS insole. CONCLUSIONS: Dr. Scholl's Active Series insoles
      demonstrate efficacy in reducing VLRs, which are associated with plantar
      fasciitis. Biomechanical changes to variables associated with tibial stress
      syndrome (AEVs, AEAs) and patellofemoral pain syndrome (KAAIs) were inconsistent.

PMID- 29035980
TI  - Incidence of Symptomatic Pulmonary Embolus and Deep Vein Thrombosis After Knee
      Arthroscopy in the Pediatric and Adolescent Population.
AB  - OBJECTIVE: The incidence of deep venous thrombosis (DVT) and pulmonary embolism
      (PE) after pediatric knee arthroscopy is unknown. The purpose of this study was
      to determine the incidence of venous thromboembolism (VTE) after knee arthroscopy
      in the pediatric and adolescent population in a high-volume center. DESIGN:
      Retrospective cohort study. SETTING: Tertiary care children's hospital. PATIENTS:
      All patients who underwent arthroscopy of the knee for a sports-related injury by
      2 surgeons were reviewed. Chief complaint, past medical/surgical history,
      medications, procedure performed, intraoperative findings, intraoperative
      complications, and postoperative recovery were reviewed. The incidences of
      postoperative VTE within 30 days after the procedure were reviewed. RESULTS:
      Seven hundred forty-six (358 male and 388 female patients) knee arthroscopies
      performed from September 2011 to October 2016 by 2 pediatric orthopedic surgeons
      specializing in sports-related injuries were included. The average age was 15.2
      +/- 2.72 years. Five patients were suspected to have either DVT or PE
      postoperatively (0.67%). The overall incidence of symptomatic confirmed VTE after
      knee arthroscopic procedures was 0.27% (one DVT after a partial lateral
      meniscectomy and one PE after fixation of an osteochondral lesion). CONCLUSIONS:
      The incidence of VTE after pediatric sports medicine knee arthroscopies is low,
      0.27%. Patients who present with calf swelling or pain, chest pain, or shortness
      of breath after arthroscopic surgery should be examined closely. LEVEL OF
      EVIDENCE: Level III.

PMID- 29035981
TI  - Clinical Utility of Oculomotor and Electrophysiological Measures in Identifying
      Concussion History.
AB  - OBJECTIVE: To examine whether oculomotor and electrophysiological measures
      improve the clinical performance of the typical concussion protocol for
      classifying collegiate athletes with a history of concussion. DESIGN: Cross
      sectional. SETTING: University Athletic Medicine and Research Facility.
      PARTICIPANTS: Forty-five varsity collegiate athletes. INDEPENDENT VARIABLES:
      Collegiate varsity athletes with or without a history of a diagnosed concussion.
      MAIN OUTCOME MEASURES: Multivariate receiver operating curve and area under the
      curve (AUC) analyses tested the clinical performance of the typical concussion
      protocol (symptoms, postural control, neuropsychological abilities). We examined
      differences in clinical performance between this protocol and after adding
      reflexive saccade and event-related potential (ERP) indices. Hypotheses were
      formed after data collection. RESULTS: Significant AUCs were demonstrated for the
      typical concussion protocol (model 1: AUC = 0.75, P = 0.007), after adding
      reflexive saccade eye excursion gain (model 2: AUC = 0.80, P = 0.001), and ERPs
      (model 3: AUC = 0.79, P = 0.002). The AUC for reflexive saccades and ERPs was
      significant (model 4: AUC = 0.70, P = 0.030). Model 2's increased clinical
      performance compared with model 1 was nonsignificant, chi(2) = 1.871, P = 0.171.
      CONCLUSIONS: All 4 models demonstrated adequate sensitivity and specificity for
      classifying athletes with a previous concussion. Adding reflexive saccades and
      ERPs did not significantly increase clinical performance of the typical
      concussion protocol. Future research should determine the clinical utility of
      saccades and ERPs for acute postconcussion assessments.

PMID- 29035982
TI  - Comparison of the Effect of 5 Different Treatment Options for Managing Patellar
      Tendinopathy: A Secondary Analysis.
AB  - OBJECTIVE: Currently, no treatments exist for patellar tendinopathy (PT) that
      guarantee quick and full recovery. Our objective was to assess which treatment
      option provides the best chance of clinical improvement and to assess the
      influence of patient and injury characteristics on the clinical effect of these
      treatments. DESIGN: A secondary analysis was performed on the combined databases
      of 3 previously performed double-blind randomized controlled trials. PATIENTS: In
      total, 138 patients with PT were included in the analysis. INTERVENTIONS:
      Participants were divided into 5 groups, based on the treatment they received:
      Extracorporeal shockwave therapy (ESWT) (n = 31), ESWT plus eccentric training (n
      = 43), eccentric training (n = 17), topical glyceryl trinitrate patch plus
      eccentric training (n = 16), and placebo treatment (n = 31). MAIN OUTCOME
      MEASURES: Clinical improvement (increase of >=13 points on the Victorian
      Institute of Sport Assessment-Patella score) after 3 months of treatment.
      RESULTS: Fifty-two patients (37.7%) improved clinically after 3 months of
      treatment. Odds ratios (ORs) for clinical improvement were significantly higher
      in the eccentric training group (OR 6.68, P = 0.009) and the ESWT plus eccentric
      training group (OR 5.42, P = 0.015) compared with the other groups. We found
      evidence that a high training volume, a longer duration of symptoms, and older
      age negatively influence a treatment's clinical outcome (trend toward
      significance). CONCLUSIONS: Our study confirmed the importance of exercise, and
      eccentric training in particular, in the management of PT. The role of ESWT
      remains uncertain. Further research focusing on the identified prognostic factors
      is needed to be able to design patient-specific treatment protocols for the
      management of PT.

PMID- 29035983
TI  - Injury Pattern in Icelandic Elite Male Handball Players.
AB  - OBJECTIVE: To examine the incidence, type, location, and severity of injuries in
      Icelandic elite male handball players and compare across factors like physical
      characteristics and playing position. DESIGN: Prospective cohort study. SETTING:
      The latter part of the preseason and the competitive season of Icelandic male
      handball. PARTICIPANTS: Eleven handball teams (185 players) from the 2 highest
      divisions in Iceland participated in the study. Six teams (109 players) completed
      the study. VARIABLES MEASURED: Injuries were recorded by the players under
      supervision from their team physiotherapists or coaches. Coaches recorded
      training exposure, and match exposure was obtained from the Icelandic and
      European Handball Federations. The players directly recorded potential risk
      factors, such as age, height, weight, previous injuries, and player position.
      MAIN OUTCOME MEASURES: Injury incidence and injury location and number of injury
      days. RESULTS: Recorded time-loss injuries were 86, of which 53 (62%) were acute
      and 33 (38%) were due to overuse. The incidence of acute injuries was 15.0
      injuries/1000 hours during games and 1.1 injuries/1000 hours during training
      sessions. No significant difference was found in injury incidence between teams,
      but number of injury days did differ between teams (P = 0.0006). Acute injuries
      were most common in knees (26%), ankles (19%), and feet/toes (17%), but overuse
      injuries occurred in low back/pelvic region (39%), shoulders (21%), and knees
      (21%). Previous knee injuries were the only potential risk factor found for knee
      injury. CONCLUSIONS: The results indicate a higher rate of overuse injuries in
      low back/pelvic region and shoulders than in comparable studies.

PMID- 29035984
TI  - Risk Factors for Lower-Extremity Injuries Among Contemporary Dance Students.
AB  - OBJECTIVE: To determine whether student characteristics, lower-extremity
      kinematics, and strength are risk factors for sustaining lower-extremity injuries
      in preprofessional contemporary dancers. DESIGN: Prospective cohort study.
      SETTING: Codarts University of the Arts. PATIENTS: Forty-five first-year students
      of Bachelor Dance and Bachelor Dance Teacher. ASSESSMENT OF RISK FACTORS: At the
      beginning of the academic year, the injury history (only lower-extremity) and
      student characteristics (age, sex, educational program) were assessed using a
      questionnaire. Besides, lower-extremity kinematics [single-leg squat (SLS)],
      strength (countermovement jump) and height and weight (body mass index) were
      measured during a physical performance test. MAIN OUTCOME MEASURES: Substantial
      lower-extremity injuries during the academic year were defined as any problems
      leading to moderate or severe reductions in training volume or in performance, or
      complete inability to participate in dance at least once during follow-up as
      measured with the Oslo Sports Trauma Research Center (OSTRC) Questionnaire on
      Health Problems. Injuries were recorded on a monthly basis using a questionnaire.
      Analyses on leg-level were performed using generalized estimating equations to
      test the associations between substantial lower-extremity injuries and potential
      risk factors. RESULTS: The 1-year incidence of lower-extremity injuries was
      82.2%. Of these, 51.4% was a substantial lower-extremity injury. Multivariate
      analyses identified that ankle dorsiflexion during the SLS (OR 1.25; 95%
      confidence interval, 1.03-1.52) was a risk factor for a substantial lower
      extremity injury. CONCLUSIONS: The findings indicate that contemporary dance
      students are at high risk for lower-extremity injuries. Therefore, the identified
      risk factor (ankle dorsiflexion) should be considered for prevention purposes.

PMID- 29035985
TI  - QT Corrections for Long QT Risk Assessment: Implications for the Preparticipation
      Examination.
AB  - BACKGROUND: Because sudden cardiac death (SCD) in the young mainly occur in
      individuals with structurally normal hearts, improved screening techniques for
      detecting inherited arrhythmic diseases are needed. The QT interval is an
      important screening measurement; however, the criteria for detecting an abnormal
      QT interval are based on Bazett formula and older populations. OBJECTIVE: To
      define the normal upper limits for QT interval from the electrocardiograms (ECGs)
      of healthy young individuals, compare the major correction formula and propose
      new QT interval thresholds for detecting those at risk of SCD. METHODS: Young
      active individuals underwent ECGs as part of routine preparticipation physical
      examinations for competitive sports or community screening. This was a nonfunded
      study using de-identified data with no follow-up. RESULTS: There were 31 558
      subjects: 2174 grade school (7%), 18 547 high school (59%), and 10 822 college
      (34%). Mean age was 17 (12-35 years), 45% were female, 67% white, and 11% of
      African descent. Bazett performed least favorably for removing the effect of
      heart rate (HR), whereas Fridericia performed the best. Fridericia correction
      also closely fit the raw data best (R of 0.65), and at percentile values
      applicable to screening. The recommended risk cut points using Bazetts correction
      identified less than half of the athletes in the 99th or 99.5th percentiles of
      the uncorrected QT by HR range. Use of Fridericia correction increased capture
      rates by over 50%. CONCLUSION: Our results support the application of the
      Fridericia-corrected threshold of 460 for men and 470 milliseconds for women (and
      485 milliseconds for marked prolongation) rather than Bazett correction for the
      preparticipation examination.

PMID- 29035986
TI  - Long-Term Outcome of Mini-Open Surgical Decompression for Chronic Exertional
      Compartment Syndrome of the Forearm in Professional Motorcycling Riders.
AB  - OBJECTIVE: To evaluate results of mini-open fasciotomy (MOF) in high-level
      motorcycling or motocross riders with chronic exertional compartment syndrome
      (CECS) at long-term follow-up (minimum 5 years). DESIGN: Case series. LEVEL OF
      EVIDENCE: IV. SETTING: University Hospital/Private Practice. PATIENTS: Fifty-four
      professional motorcycling riders treated with MOF for a CECS of the forearm from
      January 2006 to June 2011. Inclusion criteria comprised: high-level motorcycling
      or motocross riders, clinical symptoms of CECS for at least 6 months, diagnosis
      confirmed using preoperative compartment hydrostatic pressure measurement and/or
      magnetic resonance imaging of the forearm, minimum follow-up of 5 years.
      INTERVENTIONS: A MOF to obtain decompression of all compartments was performed in
      all patients. MAIN OUTCOME MEASURES: Visual analog scale; a subjective scale to
      measure strength; QuickDash functional scores. Time to resume full riding
      capacities as short-term evaluation. RESULTS: A total of 54 patients who
      underwent 77 MOF procedures overall (23 bilateral) were included. The mean age
      was 23.6 +/- 5.2 years. Mean Visual Analog Scale decreased from a preoperative
      value of 68.2 to a 3-month postoperative value of 26 (P < 0.001). Mean QuickDash
      scale was 84 at preoperative registration, falling to 20, 3 months after surgery
      (P < 0.001) and down to 12 at 1-year follow-up (P = 0.017). The average time to
      return to full riding capacities was 3.5 +/- 1 week. CONCLUSIONS: Mini-open
      fasciotomy resulted safe and effective for the treatment of chronic exertional
      compartment syndrome in high-level motorcycling or motocross riders. The good
      outcome at follow-up resulted stable at 5 years and the incidence of
      complications remained low. Our data demonstrate that the resolution of symptoms
      is reliable and durable. Pain recovery was immediate after surgery, instead
      functional scores showed a more gradual recovery throughout the 12 months after
      surgery. CLINICAL RELEVANCE: Mini-open fasciotomy is a reliable treatment for
      CECS of the forearm in professional motorcycling riders. This treatment should
      also be considered in young riders due to the absence of tardive relapse reported
      in this study.

PMID- 29035987
TI  - Low-Intensity Pulsed Ultrasound for Early-Stage Lumbar Spondylolysis in Young
      Athletes.
AB  - OBJECTIVE: To examine the effect of low-intensity pulsed ultrasound (LIPUS) on
      early-stage spondylolysis in young athletes. DESIGN: Case-control study. SETTING:
      A single outpatient orthopedic and sports clinic. PATIENTS: A total of 82 young
      athletes (80 boys and 2 girls; mean age, 14.8 years; range, 10-18 years) with
      early-stage lumbar spondylolysis were enrolled in this study. All patients were
      examined by plain radiography and magnetic resonance imaging. INTERVENTIONS:
      Patients received either standard conservative treatment combined with LIPUS (n =
      35) or without LIPUS (n = 47), according to the sequence of admission. The
      standard conservative treatment included thoracolumbosacral brace, sports
      modification, and therapeutic exercise. MAIN OUTCOME MEASURES: The time required
      to return to previous sports activities was analyzed by using Kaplan-Meier
      methods with the log-rank test. RESULTS: The baseline parameters of both groups
      were not significantly different. The median time to return to previous sports
      activities was 61 days [95% confidence interval (CI): 58-69 days] in the group
      treated with LIPUS, which was significantly shorter than that of the group
      treated without LIPUS (167 days, 95% CI: 135-263 days; P < 0.01). CONCLUSIONS:
      These results suggest that LIPUS combined with conservative treatment for early
      stage lumbar spondylolysis in young athletes could be a useful therapy for quick
      return to playing sports.

PMID- 29035988
TI  - Helmet Use and Risk-Taking Behavior Among Skiers and Snowboarders.
AB  - OBJECTIVE: To characterize factors associated with helmet use and risk-taking
      behavior among recreational skiers and snowboarders. DESIGN: Observational study.
      SETTING: Large, western United States mountain resort. PARTICIPANTS: 1285 male
      and female recreational skiers and snowboarders were interviewed during a single
      winter ski season. INDEPENDENT VARIABLES: Helmet use, demographic, and sport
      related characteristics. MAIN OUTCOME MEASURES: Brief sensation seeking scale
      (BSSS) as a measure of risk-taking behavior and self-reported risk compensation.
      RESULTS: Of the respondents (N = 1285), 17.5%, 12.5%, and 70.0% reported that
      they never, sometimes, and always wore a helmet, respectively. Multiple linear
      regression analysis showed that individuals reporting sometimes wearing a helmet
      had significantly higher BSSS scores than those reporting never wearing a helmet
      (P = 0.031) or always wearing it (P = 0.018). Male gender, younger age,
      snowboarding, higher perceived sport ability, more days per year skiing or
      snowboarding, and more time spent in the terrain park were significantly
      associated with higher BSSS scores (P < 0.05). Logistic regression analysis
      focusing on subgroups of respondents who reported either sometimes or always
      wearing a helmet indicated that the odds of taking more risks when wearing a
      helmet for inconsistent helmet users was 75% higher than the odds for those who
      reported always wearing a helmet (P = 0.06). CONCLUSIONS: Inconsistent helmet
      users have characteristics of risk-taking behavior and risk compensation. Male
      gender, younger age, snowboarding, higher perceived sport ability, and more time
      spent on the mountain and in the terrain park are also important determinants of
      risk-taking behavior.

PMID- 29035989
TI  - "It Doesn't Make Sense for Us Not to Have One"-Understanding Reasons Why
      Community Sports Organizations Chose to Participate in a Funded Automated
      External Defibrillator Program.
AB  - OBJECTIVE: Implementation of automated external defibrillators (AEDs) in
      community sports settings is an important component of emergency medical
      planning. This study aimed to understand motivations for why sports organizations
      participated in a government-funded program that provided AEDs and associated
      first-aid training. DESIGN: Face-to-face interviews. SETTING: Community sports
      organizations in Victoria, Australia. PARTICIPANTS: Representatives from 14
      organizations who participated in a government-funded AED program. MAIN OUTCOME
      MEASURES: Motivations to participate in the AED program were explored using a
      qualitative descriptive approach. RESULTS: Two overarching themes emerged:
      awareness of the program and decision to apply. Awareness was gained indirectly
      through grant advertising in newsletters/emails/web sites and directly through
      their sporting associations. For most organizations, there was no decision
      process per se, rather, the opportunity to apply was the key determinant for
      participating in the program. A duty of care also emerged as a key driving
      factor, with recognition of AEDs as a valuable asset to communities broadly, not
      just the participants' immediate sports setting. Reflecting on participation in
      the program, these participants identified that it was important to increase
      awareness about AED ownership and use. The program benefits were clearly summed
      up as being best prepared for a worst-case scenario. DISCUSSION: This study
      provides new understanding of why community sports organizations apply for an AED
      and training. The strongest reason was simply the opportunity to acquire this at
      no cost. Therefore, for wider implementation of AEDs, additional funding
      opportunities, targeted awareness of these opportunities, and continued promotion
      of AED importance are recommended.

PMID- 29035990
TI  - Interruption of the Inferior Vena Cava With Azygos Continuation.
AB  - This report describes a 19-year-old man with interruption of the inferior vena
      cava with azygos continuation. Both radionuclide venography and MRI clearly
      showed venous return of the lower limbs through prominent collateral systems.

PMID- 29035991
TI  - Myocardial Perfusion SPECT and Cardiac MR Correlative Imaging.
AB  - An institutional review board-approved retrospective review of 55 patients who
      received cardiac MRI within 1 year of myocardial SPECT was performed. Forty-nine
      demonstrated myocardial infarction by MRI. MRI and SPECT agreed in all but 1
      case, where SPECT preceded MRI by 97 days. Three cases are presented here: 2
      demonstrating congruent MRI and SPECT changes in a vascular distribution status
      post infarction and a third with a nonvascular pattern of abnormalities related
      to left ventricular aneurysm in cardiac sarcoidosis. It is useful to review and
      correlate myocardial SPECT with available cardiac MRI, especially in patients
      with matching perfusion defects.

PMID- 29035992
TI  - 18F-FAZA PET/CT Hypoxia Imaging of High-Grade Glioma Before and After
      Radiotherapy.
AB  - A 57 year-old man underwent MRI with dynamic susceptibility contrast and dynamic
      contrast-enhanced perfusion for neurological symptoms suggesting the diagnosis of
      high-grade glioma. A F-FAZA PET/CT was performed because of the enrollment in a
      prospective clinical trial. Subsequent radiotherapy treatment has been planned
      based on conventional imaging; moreover, a F-FAZA PET/CT-guided treatment
      planning highlighting hypoxic regions has been simulated. After radiotherapy
      treatment, the man underwent MRI and F-FAZA PET/CT, showing partial response.

PMID- 29035993
TI  - Uncommon Metastasis to the Pancreas From Adenocarcinoma of the Cervix Detected on
      Surveillance 18F-FDG PET/CT Imaging.
AB  - F-FDG PET/CT is a sensitive noninvasive imaging tool for assessment of recurrent
      disease in patients with carcinoma cervix. Its role in early detection of
      recurrences especially in asymptomatic patients has been demonstrated well in
      literature. Metastatic involvement of the pancreas in patients with
      adenocarcinoma of the cervix is a rare occurrence, reported only few times in
      literature, and is predominantly documented to be associated with uncommon
      histopathologies such as neuroendocrine and small cell carcinoma. We report a
      rare asymptomatic case of adenocarcinoma of the cervix, detected and confirmed to
      have pancreatic metastasis on surveillance FDG PET/CT imaging.

PMID- 29035994
TI  - Prostate-Specific Membrane Antigen in Low-Grade Fibromatosis.
AB  - We report a case of fibromatosis demonstrating prostate-specific membrane antigen
      (PSMA)-positive scan. A 76-year-old man was under assessment because of rising
      prostate-specific antigen level. Bone scan showed abnormal soft tissue uptake of
      Tc-MDP adjacent to the right scapula, compatible with a mass in MRI, thereafter.
      Because of the unavailability of Ga-PSMA scan in our department and also high
      cost in other centers, the patient underwent Lu-PSMA for more assessment, which
      revealed PSMA-avid mass. Pathologic examination confirmed the diagnosis of low
      grade fibromatosis. This report demonstrates another false-positive result of
      PSMA scan and highlights the importance of pathologic examination.

PMID- 29035995
TI  - Internal Auditory Canal Tumor as an Incidental Finding on a Choline PET/CT Scan
      in a Prostate Cancer Patient.
AB  - An 84-year-old man with a history of prostate cancer, treated with radiotherapy,
      presented with an increase in PSA levels. F-choline PET/CT showed foci of
      increased choline uptake in L4 and L5 vertebrae, suggestive of bone metastases
      and another focus in the right cerebellopontine angle. A brain MRI revealed a
      focus of intense contrast enhancement in the same region, consistent with an
      acoustic neuroma.

PMID- 29035996
TI  - Radioguided Occult Lesion Localization: Technical Procedures and Clinical
      Applications.
AB  - PURPOSE: Regarding radioguided surgery, the concept of "radioguided occult lesion
      localization" (ROLL) is based on both preoperative interventional imaging and
      intraoperative radioguided detection of a clinically occult neoplastic lesion.
      METHODS: This methodology consists in the direct administration into the lesion
      of Tc-macroaggregated human albumin formed by relatively large particles retained
      at the injection site, which direct radioguided excisional biopsy. RESULTS: This
      modality has expanded from the classic application of ROLL for nonpalpable breast
      lesions to other tumors, such as solitary pulmonary nodules or recurrences from
      differentiated thyroid carcinoma. In 2011, in order to improve the classification
      of different radioguided surgical procedures, ROLL applications were included in
      the more complete concept of GOSTT (Guided intraOperative Scintigraphic Tumor
      Targeting). This concept was introduced to include the entire range of basic and
      advanced radioguided procedures necessary to supply a "road map" for the surgeon.
      CONCLUSIONS: The terms ROLL and GOSTT have further developed by incorporating
      novel modalities such as hybrid tracers for simultaneous fluorescence and
      radioactive signal detection and innovative navigation systems based on mixed
      reality protocols.

PMID- 29035997
TI  - Stewart-Treves Syndrome on the Lower Extremity Associated to Idiopathic Chronic
      Lymphedema Visualized on FDG PET/CT.
AB  - Angiosarcomas are highly malignant and rare tumors of vascular or lymphatic
      endothelial cell origin with a poor prognosis. Lymphangiosarcoma associated with
      chronic lymphedema is known as Stewart-Treves syndrome. Stewart-Treves syndrome
      is primarily described in patients with lymphedema of an upper extremity
      occurring after breast cancer surgery including radical axillary lymph node
      dissection and subsequent radiotherapy. It is rarely described in the presence of
      idiopathic chronic lymphedema of the lower extremities. We present a case of
      lymphangiosarcoma visualized on F-FDG PET/CT, where Stewart-Treves syndrome is
      secondary to probably a combination of idiopathic chronic lymphedema of the lower
      extremities and systemic immunosuppressive treatment.

PMID- 29035998
TI  - Uterine Metastasis From Gastric Adenocarcinoma Masquerading as Physiologic
      Endometrial Uptake in FDG PET/CT.
AB  - A 44-year-old woman with newly diagnosed gastric adenocarcinoma by gastroscopy
      underwent F-FDG PET/CT to evaluate possible metastasis. The images demonstrated
      intense activity in the region of uterine corpus, as well as greater gastric
      curvature. Physiologic uptake of endometrium was initially suspected, given the
      rarity with which extragenital cancers metastasize to the uterus. Ultimately, the
      endometrium proved to be mucinous adenocarcinoma of gastric origin based on its
      shared histological features and compatible immunostaining profile.

PMID- 29035999
TI  - Effects on 18F-FDG PET/CT Brain Glucose Metabolism in Rectal Cancer Patients
      Undergoing Neoadjuvant Chemotherapy.
AB  - PURPOSE: Retrospective study of the effects of anticancer treatment on the brain
      metabolism of patients diagnosed with rectal cancer based on a large and
      homogeneous sample of 40 paired F-FDG PET/CT volumes taken from 20 patients. The
      results are compared to the ones presented by related works to help elucidating
      the mechanisms of neurotoxicity associated to a decrease in memory, learning and
      motor skills. PATIENTS AND METHODS: Twenty patients with rectal adenocarcinoma
      were scanned before and after neoadjuvant chemoradiation based exclusively on 5
      fluorouracil and leucovorin. The sample was non-rigidly registered to a common
      template to allow for the comparison of regional metabolism. Statistical analysis
      was based on adjusted paired t-tests. RESULTS: The analysis primarily revealed a
      statistically significant decrease in the metabolism after neoadjuvant
      chemotherapy at the hypothalamus, putamen, head of the caudate, globus pallidus,
      red nucleus, substantia nigra, amygdala, cerebellum and the parahippocampal
      gyrus. The analysis also revealed smaller regions of increased metabolic activity
      at the middle temporal gyrus, precuneus of the parietal lobe and cuneus of the
      occipital lobe. CONCLUSIONS: The regions of decreased metabolism detected in the
      study are related to memory, learning and voluntary movement which is consistent
      with previous findings based on clinical studies and neuropsychological tests
      that report impairments on neurocognitive and motor skills associated to these
      therapies.

PMID- 29036000
TI  - Unilateral Submandibular Gland Atrophy and Sialolithiasis Diagnosed on 99mTc-MIBI
      SPECT/CT in a Patient With Primary Hyperparathyroidism.
AB  - A variety of sequelae of elevated calcium levels are encountered in patients with
      underlying primary hyperparathyroidism, including stone formation such as calculi
      in the urinary tract and sialoliths in the salivary glands and ducts. We present
      a case of a 54-year-old woman with fatigue, myalgia, and poor concentration who
      was found to have hypercalcemia (corrected calcium, 11.2 mg/dL) and elevated
      parathyroid hormone level (112 pg/mL), laboratory values consistent with primary
      hyperparathyroidism. She underwent evaluation with a Tc-MIBI parathyroid SPECT
      scan that included x-ray CT acquisitions for anatomical localization and
      attenuation correction.

PMID- 29036001
TI  - Atlas of Extraosseous Findings Detected by 18F-NaF PET/CT Bone Scan.
AB  - F-NaF PET/CT is an evolving technique that provides high sensitivity for
      detection of osseous metastases. In addition to detecting pathological osseous
      lesions, F uptake is occasionally detected in extraosseous lesions. However,
      reporting of extraosseous uptake in the literature is limited, and the increasing
      use of F-NaF PET/CT dictates that interpreting physicians learn to recognize
      extraosseous findings. An atlas of extraosseous findings detected by F-NaF PET/CT
      is presented, which includes cases under 2 broad categories: nonneoplastic and
      neoplastic.

PMID- 29036002
TI  - Multimodal Imaging in Klippel-Trenaunay-Weber Syndrome: Clinical Photography,
      Computed Tomoangiography, Infrared Thermography, and 99mTc-Phytate
      Lymphoscintigraphy.
AB  - We report the case of a 19-year-old man who presented with a 12-year history of
      progressive fatigue, feeling hot, excessive sweating, and numbness in the left
      arm. He had undergone multimodal imaging and was diagnosed as having Klippel
      Trenaunay-Weber syndrome (KTWS). This is a rare congenital disease, defined by
      combinations of nevus flammeus, venous and lymphatic malformation, and
      hypertrophy of the affected limbs. Lower extremities are affected mostly.
      Conventional modalities for evaluating KTWS are ultrasonography, CT, MRI,
      lymphoscintigraphy, and angiography. There are few reports on multimodal imaging
      of upper extremities of KTWS patients, and this is the first report of an
      infrared thermography in KTWS.

PMID- 29036003
TI  - 68Ga-Prostate-Specific Membrane Antigen-Avid Tubercular Lesions Mimicking
      Prostate Cancer Metastasis on Simultaneous Prostate-Specific Membrane Antigen
      PET/MRI.
AB  - Ga-prostate-specific membrane antigen (PSMA) has gained increasing interest as a
      target molecule in imaging of prostate cancer because of its selective
      overexpression in local prostate cancer lesions and metastasis. We report a case
      of a 62-year-old man with raised serum prostate-specific antigen levels who
      presented for Ga-PSMA HBED-CC simultaneous PET/MRI for prostate cancer
      evaluation. A PSMA-nonavid PI-RADS 5 (Prostate Imaging-Reporting and Data System)
      lesion was confirmed as adenocarcinoma on histopathology. The PSMA-avid lesions
      were noted in the calvarium and lung, with the calvarial lesion confirmed to be
      of tubercular etiology on biopsy, and both lesions subsequently responded to
      antitubercular treatment.

PMID- 29036004
TI  - The utility of clinical ultrasonography in identifying distal forearm fractures
      in the pediatric emergency department.
AB  - OBJECTIVE: The aim of this study is to evaluate the utility of Point-Of-Care
      Ultrasound (POCUS) for diagnosing distal forearm fractures in pediatric emergency
      departments (ED). PATIENTS AND METHODS: A prospective observational study was
      carried out in children aged younger than 15 years attended in an ED with an
      indication of radiography because of a suspected distal forearm fracture. The
      POCUS was performed considering cortical irregularity or disruption compatible
      with fracture. Then, the radiography was requested and the patient was evaluated
      by an ED traumatologist. Both tests were blinded to each other. The radiograph
      was considered to be the reference diagnostic test. Diagnostic validation tests
      were performed. RESULTS: A total of 115 patients [mean age: 9.1 (SD: 3.1) years;
      50.4% males] were included, with 57 of these presenting fractures: 42 (73.7%)
      single bone fractures and 15 (26.3%) combined fractures of the radius and ulna.
      As such, 72 fractures were detected (prevalence 31.3%). The sensitivity and
      specificity of POCUS for detecting fractures were 94.4% [95% confidence interval
      (CI): 86.4-98.5] and 96.8% (95% CI: 92.8-99.0), respectively. The positive and
      negative predictive values were 93.2% (95% CI: 84.7-97.7) and 97.5% (95% CI: 93.6
      99.3), respectively. CONCLUSION: POCUS enables the clinical diagnosis of distal
      forearm fractures in ED. In addition, this is a highly accurate technique that
      can be applied easily by the ED pediatrician. As such, its inclusion as part of
      the physical examination could improve the accuracy of the clinical diagnosis and
      the global management of the patient.

PMID- 29036005
TI  - In-Office Sutureless Correction of Prolapsed Subconjunctival Orbital Fat.
AB  - PURPOSE: To describe a minimally invasive, sutureless, small incision surgical
      technique for the treatment of subconjunctival orbital fat prolapse (SOFP)
      performed using local anesthesia in an office setting. METHODS: Retrospective
      study of the surgical outcome of 45 patients with either bilateral or unilateral
      SOFP treated by a single surgeon (R.S.) between July 2010 and February 2015.
      RESULTS: Forty-five patients (39 male, 6 female) had a mean age of 67 years. Fat
      prolapse was bilateral in 23 patients (51%). A total of 68 eyes were operated on.
      All surgeries were without any intra- or postoperative complications such as
      infection, dry-eye symptoms, ocular motility impairment, or recurrence with a
      mean follow up of 37 months. All patients had a favorable postoperative cosmetic
      improvement. CONCLUSIONS: The authors propose an office-based, cost-effective,
      minimally invasive, sutureless technique for treating SOFP with local anesthesia
      in a safe and effective manner. The lack of complications or recurrence with an
      adequate follow-up period following this technique is encouraging. Surgeons
      should consider this technique in the surgical correction of SOFP.

PMID- 29036007
TI  - Trends of Cholecystectomies for Presumed Biliary Dyskinesia in Children in the
      United States.
AB  - BACKGROUND: Biliary dyskinesia (BD) is a controversial clinical entity.
      Standardized diagnostic test and management guidelines are lacking in children.
      Published data suggest that long-term outcomes of surgical and medical management
      are similar. We sought to determine national population-based trends of
      cholecystectomies performed in children for BD and associated healthcare
      expenditure in the United States during a 10-year period. METHODS: Using
      Nationwide Inpatient Sample and the International Classification of Diseases, the
      9th revision clinical modification codes, we identified children who had a
      cholecystectomy for BD from 2002 to 2011 in the United States. RESULTS: A total
      of 66,380 cholecystectomies were identified as primary procedural diagnosis using
      weighted analysis from 2002 to 2011 in children. BD was the primary indication
      for cholecystectomy in 6674 (10.8%) of the patients. During the study period, the
      number of cholecystectomies performed for BD in children increased from 6.6% in
      2002 to 10.6% in 2011, and a majority were adolescent white females. The annual
      health care expenditure for surgical management of BD for children in the US was
      estimated to almost $16 million/year. CONCLUSIONS: Despite lack of standardized
      diagnostic criteria and variable outcomes of surgical intervention reported in
      pediatric literature, cholecystectomies are commonly performed for children with
      BD in the United States. Consensus guidelines for the diagnosis and management of
      this controversial disorder in children are needed.

PMID- 29036006
TI  - Blood Perfusion in Human Eyelid Skin Flaps Examined by Laser Speckle Contrast
      Imaging-Importance of Flap Length and the Use of Diathermy.
AB  - PURPOSE: It is well known that blood perfusion is important for the survival of
      skin flaps. As no study has been conducted to investigate how the blood perfusion
      in human eyelid skin flaps is affected by the flap length and diathermy, the
      present study was carried out to investigate these in patients. METHODS: Fifteen
      upper eyelids were dissected as part of a blepharoplastic procedure, releasing a
      30-mm long piece of skin, while allowing the 5 mm wide distal part of the skin to
      remain attached, to mimic a skin flap (hereafter called a "skin flap"). Blood
      perfusion was measured before and after repeated diathermy, using laser speckle
      contrast imaging. RESULTS: Blood perfusion decreased from the base to the tip of
      the flap: 5 mm from the base, the perfusion was 69%, at 10 mm it was 40%, at 15
      mm it was 20%, and at 20 mm it was only 13% of baseline values. Diathermy further
      decreased blood perfusion (measured 15 mm from the base) to 13% after applying
      diathermy for the first time, to 6% after the second and to 4% after the third
      applications of diathermy. CONCLUSIONS: Blood perfusion falls rapidly with
      distance from the base of skin flaps on the human eyelid, and diathermy reduces
      blood perfusion even further. Clinically, it may be advised that flaps with a
      width of 5 mm be no longer than 15 mm (i.e., a width:length ratio of 1:3), and
      that the use of diathermy should be carefully considered.

PMID- 29036009
TI  - Exchangeable Zinc Pool Size at Birth in Pakistani SGA and AGA Infants Do Not
      Differ but are Lower than in US Infants.
AB  - OBJECTIVES: Small for gestational age (SGA) infants are more susceptible to
      infectious morbidity and growth faltering compared to their appropriate for
      gestational age (AGA) counterparts. Zinc supplementation of SGA infants may be
      beneficial but the underlying susceptibility to zinc deficiency of SGA infants
      has not been examined. METHODS: In a community-based, observational, longitudinal
      study in a peri-urban settlement of Karachi, Pakistan, we compared the size of
      the exchangeable zinc pools (EZP) in term SGA and AGA infants at birth and at 6
      months of age, hypothesizing that the EZP would be lower in the SGA group. To
      measure EZP size, a zinc stable isotope was intravenously administered within 48
      hours of birth (n = 17 and 22) at 6 months (n = 11 and 14) in SGA and AGA
      infants, respectively. Isotopic enrichment in urine was used to determine EZP.
      RESULTS: No significant difference was detected in the mean (+/- SD) EZP between
      SGA and AGA infants at birth, with values of 9.8 +/- 3.5 and 10.1 +/- 4.1 mg/kg,
      respectively (p = 0.86), or at 6 months. Longitudinal EZP measurements
      demonstrated a significant decline in EZP relative to body weight in both groups
      at 6 months (p < 0.001). Mean EZP (adjusted for body weight) size at birth for
      the combined Pakistani groups was significantly lower than U.S. AGA infants at
      birth (p = 0.017). CONCLUSIONS: These results did not support a difference in
      zinc endowment between SGA and AGA Pakistani infants. However, they do suggest
      lower in utero zinc transfer to the fetus in a setting where poor maternal
      nutritional status may confer a high susceptibility to postnatal zinc deficiency.

PMID- 29036008
TI  - Ethnic Disparity in the Incidence and Outcome of Biliary Atresia in New Zealand.
AB  - To determine incidence and outcome of biliary atresia (BA) between ethnic groups
      in New Zealand (NZ), a retrospective review was undertaken of children with BA
      born between 2002 and 2014. Prioritized ethnicity was used to determine ethnicity
      and was compared to population data. Uni- and multivariate analyses were
      undertaken to determine demographic and biochemical factors associated with
      outcome. Overall incidence was 1 in 9181 (Maori 1 in 5285; European 1 in 16,228;
      P < 0.0001). Overall and transplant-free survival rates at 1, 2, and 5 years were
      92%, 86%, 82% and 70%, 49%, 30% respectively with Maori having improved
      transplant-free survival (P < 0.05) despite European children undergoing Kasai
      earlier (49 vs 63 days). BA is more common in NZ than Europe and North America,
      which is attributable to a higher incidence in Maori but overall outcome is
      poorer. Maori have improved transplant-free survival compared to NZ European
      children but the reason is unknown.

PMID- 29036010
TI  - Reasoning Beyond the Potential Use of Exclusive Enteral Nutrition and Other
      Specified Diets in Children With Ulcerative Colitis.
AB  - The incidence of inflammatory bowel disease (IBD) is steadily on the rise in
      Western and in developing countries paralleling the increase of westernized
      diets, characterized by high protein and fat as well as excessive sugar intake,
      with less vegetables and fiber. Furthermore, nutrition is involved in several
      aspects of pediatric IBD, ranging from disease etiology to induction and
      maintenance of remission of disease. Exclusive enteral nutrition (EEN) has been
      shown to induce remission, including in patients with isolated colonic disease,
      and leads to mucosal healing in Crohn disease. One hypothesis for the beneficial
      effect of this modality is exclusion of dietary components thought to cause
      dysbiosis or impair innate immune mechanisms such as the mucous layer, intestinal
      permeability or colonization and adherence with adherent-invasive Escherichia
      coli. Although there is not yet definitive data illustrating a role for EEN in
      the management of active ulcerative colitis (UC), there are several lines of
      evidence that illustrate that dietary interventions may be helpful. In
      particular, the key mechanisms of the activity of EEN (namely, changes in the
      intestinal microflora in Crohn disease) are likely also relevant to UC.
      Furthermore, the use of EEN in pediatric UC patients may add to a better bone
      health. Prospective studies are now required to evaluate the role of EEN in UC in
      children.

PMID- 29036011
TI  - Evaluating the Impact of Prescription Fill Rates on Risk Stratification Model
      Performance.
AB  - BACKGROUND: Risk adjustment models are traditionally derived from administrative
      claims. Prescription fill rates-extracted by comparing electronic health record
      prescriptions and pharmacy claims fills-represent a novel measure of medication
      adherence and may improve the performance of risk adjustment models. OBJECTIVE:
      We evaluated the impact of prescription fill rates on claims-based risk
      adjustment models in predicting both concurrent and prospective costs and
      utilization. METHODS: We conducted a retrospective cohort study of 43,097 primary
      care patients from HealthPartners network between 2011 and 2012. Diagnosis and/or
      pharmacy claims of 2011 were used to build 3 base models using the Johns Hopkins
      ACG system, in addition to demographics. Model performances were compared before
      and after adding 3 types of prescription fill rates: primary 0-7 days, primary 0
      30 days, and overall. Overall fill rates utilized all ordered prescriptions from
      electronic health record while primary fill rates excluded refill orders.
      RESULTS: The overall, primary 0-7, and 0-30 days fill rates were 72.30%, 59.82%,
      and 67.33%. The fill rates were similar between sexes but varied across different
      medication classifications, whereas the youngest had the highest rate. Adding
      fill rates modestly improved the performance of all models in explaining medical
      costs (improving concurrent R by 1.15% to 2.07%), followed by total costs (0.58%
      to 1.43%), and pharmacy costs (0.07% to 0.65%). The impact was greater for
      concurrent costs compared with prospective costs. Base models without diagnosis
      information showed the highest improvement using prescription fill rates.
      CONCLUSIONS: Prescription fill rates can modestly enhance claims-based risk
      prediction models; however, population-level improvements in predicting
      utilization are limited.

PMID- 29036014
TI  - A family with two cases of melanocytic tumors and fragile X syndrome.
AB  - Fragile X syndrome (FXS), a leading cause of inherited intellectual disability,
      most commonly results from an expansion of the CGG trinucleotide repeat in the
      fragile X mental retardation 1 (FMR1) gene to more than 200 copies (full
      mutation). The FXS phenotype differs by sex and is associated with intellectual
      and cognitive impairment, characteristic physical features, epilepsy, and/or
      behavioral challenges including autism spectrum disorder. In this patient
      population, tumors involving blood cells, digestive organs, the central nervous
      system, and testes have been described, but melanocytic tumors have not been
      reported. Here, we describe two maternal cousins with FXS, one of whom has
      melanoma and the other has atypical nevus syndrome. We discuss possible
      mechanisms leading to this unusual or possibly coincidental association and the
      difficulties in the optimal treatment of FXS patients.

PMID- 29036012
TI  - A Fresh Perspective on a Familiar Problem: Examining Disparities in Knee
      Osteoarthritis Using a Markov Model.
AB  - BACKGROUND: Disparities in the presentation of knee osteoarthritis (OA) and in
      the utilization of treatment across sex, racial, and ethnic groups in the United
      States are well documented. OBJECTIVES: We used a Markov model to calculate
      lifetime costs of knee OA treatment. We then used the model results to compute
      costs of disparities in treatment by race, ethnicity, sex, and socioeconomic
      status. RESEARCH DESIGN: We used the literature to construct a Markov Model of
      knee OA and publicly available data to create the model parameters and patient
      populations of interest. An expert panel of physicians, who treated a large
      number of patients with knee OA, constructed treatment pathways. Direct costs
      were based on the literature and indirect costs were derived from the Medical
      Expenditure Panel Survey. RESULTS: We found that failing to obtain effective
      treatment increased costs and limited benefits for all groups. Delaying treatment
      imposed a greater cost across all groups and decreased benefits. Lost income
      because of lower labor market productivity comprised a substantial proportion of
      the lifetime costs of knee OA. Population simulations demonstrated that as the
      diversity of the US population increases, the societal costs of racial and ethnic
      disparities in treatment utilization for knee OA will increase. CONCLUSIONS: Our
      results show that disparities in treatment of knee OA are costly. All
      stakeholders involved in treatment decisions for knee OA patients should consider
      costs associated with delaying and forgoing treatment, especially for
      disadvantaged populations. Such decisions may lead to higher costs and worse
      health outcomes.

PMID- 29036015
TI  - Transient pituitary ACTH-dependent Cushing syndrome caused by an immune
      checkpoint inhibitor combination.
AB  - Immune checkpoint inhibitors have improved survival in numerous advanced
      malignancies, but are associated with a number of immune-related adverse events,
      including endocrinopathies. Endogenous Cushing's syndrome (CS) is a rare disorder
      resulting from exposure to high levels of circulating cortisol. CS can be caused
      either by adrenal cortex tumors or hyperplasia or by pituitary or extra-pituitary
      tumors over-secreting ACTH (known as ACTH-dependent CS). We report the first case
      of transient ACTH-dependent CS, which appeared after combined ipilimumab and
      nivolumab therapy. Our patient presented typical clinical features of CS after
      three infusions of combined therapy, high serum and daily urinary free cortisol,
      and high serum ACTH levels. Pituitary MRI showed an enlargement of the pituitary
      gland suggesting ACTH secretion of pituitary origin, which was confirmed by
      inferior petrosal sinus sampling. The pituitary findings were preceded by
      thyroiditis. The evolution was characterized by spontaneous CS regression and
      subsequent appearance of severe corticotroph deficiency consistent with
      destructive hypophysitis. Immunotherapy is a novel cause of CS.

PMID- 29036017
TI  - Patient-reported outcomes in asthma clinical trials.
AB  - PURPOSE OF REVIEW: The review provides an overview of the results of asthma
      clinical trials published in peer review journals in the last 18 months that
      evaluated patient-reported outcomes (PROs). RECENT FINDINGS: In the last 10
      years, health care moved toward a patient-centered approach, which includes
      patients' perspectives reflecting the impact of a disease and its treatment.
      SUMMARY: Surprisingly, among the almost 300 clinical trials published in the last
      one and a half year, PRO evaluation was performed in only 20 studies, and none of
      them held in a real-life setting. The effort of applying the scientific methods
      of PRO investigations in asthma clinical trials following a rigorous and
      systematic approach needs to be highly improved to allow better understanding of
      patient reported factors. Some recommendations are drawn particularly about PRO
      assessment in personalized medicine research. The ability of an individual PRO to
      evaluate choice of treatment and its effectiveness remains to be achieved.

PMID- 29036016
TI  - Exercise Preserves Physical Function in Prostate Cancer Patients with Bone
      Metastases.
AB  - PURPOSE: The presence of bone metastases has excluded participation of cancer
      patients in exercise interventions and is a relative contraindication to
      supervised exercise in the community setting because of concerns of fragility
      fracture. We examined the efficacy and safety of a modular multimodal exercise
      program in prostate cancer patients with bone metastases. METHODS: Between 2012
      and 2015, 57 prostate cancer patients (70.0 +/- 8.4 yr; body mass index, 28.7 +/-
      4.0 kg.m) with bone metastases (pelvis, 75.4%; femur, 40.4%; rib/thoracic spine,
      66.7%; lumbar spine, 43.9%; humerus, 24.6%; other sites, 70.2%) were randomized
      to multimodal supervised aerobic, resistance, and flexibility exercises
      undertaken thrice weekly (EX; n = 28) or usual care (CON; n = 29) for 3 months.
      Physical function subscale of the Medical Outcomes Study Short-Form 36 was the
      primary end point as an indicator of patient-rated physical functioning.
      Secondary end points included objective measures of physical function, lower body
      muscle strength, body composition, and fatigue. Safety was assessed by recording
      the incidence and severity of any adverse events, skeletal complications, and
      bone pain throughout the intervention. RESULTS: There was a significant
      difference between groups for self-reported physical functioning (3.2 points; 95%
      confidence interval, 0.4-6.0 points; P = 0.028) and lower body muscle strength
      (6.6 kg; 95% confidence interval, 0.6-12.7; P = 0.033) at 3 months favoring EX.
      However, there was no difference between groups for lean mass (P = 0.584), fat
      mass (P = 0.598), or fatigue (P = 0.964). There were no exercise-related adverse
      events or skeletal fractures and no differences in bone pain between EX and CON
      (P = 0.507). CONCLUSIONS: Multimodal modular exercise in prostate cancer patients
      with bone metastases led to self-reported improvements in physical function and
      objectively measured lower body muscle strength with no skeletal complications or
      increased bone pain. TRIAL REGISTRATION: ACTRN12611001158954.

PMID- 29036018
TI  - Precision medicine in asthma: linking phenotypes to targeted treatments.
AB  - PURPOSE OF REVIEW: Asthma is a heterogeneous disease consisting of different
      phenotypes that are driven by different mechanistic pathways. The purpose of this
      review is to emphasize the important role of precision medicine in asthma
      management. RECENT FINDINGS: Despite asthma heterogeneity, the approach to
      management has been on the basis of disease severity, with the most severe
      patients reserved for the maximum treatments with corticosteroids and
      bronchodilators. At the severe end, the recent availability of biologic therapies
      in the form of anti-IgE (omalizumab) and anti-IL5 therapies (mepolizumab and
      reslizumab) has driven the adaptation of precision medicine. These therapies are
      reserved for severe asthma with defined either allergic or eosinophilic
      background, respectively. SUMMARY: Unbiased definition of phenotypes or endotypes
      (which are phenotypes defined by mechanisms) is an important step towards the use
      of precision medicine in asthma. Although T2-high asthma has been defined with
      targets becoming available for treating allergic or eosinophilic asthma, the
      definition of non-T2 phenotypes remains a priority. Precision medicine is also
      dependent on the definition of biomarkers that can help differentiate between
      these phenotypes and pinpoint patients suitable for specific-targeted therapies.
      Thus, precision medicine links phenotypes (endotypes) to targeted treatments for
      better outcomes.

PMID- 29036020
TI  - Novel methods for device and adherence monitoring in asthma.
AB  - PURPOSE OF REVIEW: The article aims to provide an updated and evidence-based
      review of the innovative electronic health interventions to monitor and improve
      inhaler technique and adherence to recommended therapy in asthma. RECENT
      FINDINGS: Out of the 290 articles identified by the search strategy, 23
      manuscripts fulfilled the review inclusion criteria. Included studies mainly
      addressed m-health, electronic reminders, telemedicine, and inhaler tracker
      interventions. Investigations were performed both in adults and children.
      Remarkably, the majority of studies were performed in the most recent years,
      showing a progressively increasing interest for this field. Existing findings
      appear to be of moderate-high quality. A significant number of papers, however,
      were published in scientific journals with a low impact factor (<2). Furthermore,
      extremely high heterogeneity was found in the considered study endpoints.
      Collected evidence supports a relevant role for e-health in monitoring and
      improving inhaler use and treatment adherence in asthma. The patients' acceptance
      and satisfaction towards assessed interventions were also found to be positive.
      SUMMARY: E-health represents a highly valuable tool for achieving optimal and
      personalized asthma management. Unanimously agreed and adopted standards for
      conducting trials and reporting results on e-health in asthma are however needed
      to fully understand its real added value.

PMID- 29036019
TI  - Targeting the interleukin-4 and interleukin-13 pathways in severe asthma: current
      knowledge and future needs.
AB  - PURPOSE OF REVIEW: Severe asthma is a heterogeneous disease that can be
      classified into phenotypes and endotypes based upon clinical or biological
      characteristics. Interleukin (IL)-4 and IL-13 play a key role in type 2 (T2)
      asthma. This article reviews the signaling pathway of IL-4 and IL-13 and
      highlights its targeted therapy in severe asthma. RECENT FINDINGS: Several
      clinical trials of biologics targeting the IL-4/IL-13 pathway have recently been
      completed. In patients with severe, uncontrolled asthma, targeting IL-13 alone
      with biologics including lebrikizumab and tralokinumab has not shown consistent
      reduction in asthma exacerbations. Simultaneous targeting of both IL-4 and IL-13
      by blocking IL-4 receptor alpha using dupilumab has yielded more consistent
      results in reducing asthma exacerbations and improving lung function, especially
      in patients with increased blood eosinophils. Other biomarkers of T2 inflammation
      such as exhaled nitric oxide and serum periostin may also predict response to
      biologics targeting the IL-4/IL-13 pathway. SUMMARY: No biologic targeting the IL
      4/IL-13 pathway is currently available for treatment of asthma, but emerging data
      suggest that biologics targeting IL-4 and IL-13 together may benefit patients
      with T2 high asthma. Additional data are needed about long-term efficacy and
      safety prior to incorporating these drugs into routine clinical practice.

PMID- 29036021
TI  - The role of innate lymphoid cells in airway inflammation: evolving paradigms.
AB  - PURPOSE OF REVIEW: Innate lymphoid cells (ILCs) act as early orchestrators of the
      immune response, tissue repair, and maintenance of barrier homeostasis. This
      review summarizes recent findings of the role of ILCs in airway disease and
      highlights ongoing developments in clinical applications and treatment options.
      RECENT FINDINGS: On the basis of the transcription factors required for their
      development and cytokine profiles, ILCs have been classified into three subsets
      that resemble those of T-helper subtypes. ILCs produce multiple cytokines in
      response to signals from activated cells in their local environment. Recent
      studies in both humans and mice showed that ILCs are located at barrier surfaces
      and play critical roles in inflammatory diseases of the upper and lower airways.
      SUMMARY: The discovery of ILCs and their characterization in homeostatic and
      diseased conditions, have brought new insights into innate and adaptive immune
      responses at mucosal barrier surfaces. The recent progress in understanding the
      role of ILCs in airway inflammation directs translation of fundamental studies
      into clinical applications. This knowledge can be useful for future clinical
      practice.

PMID- 29036022
TI  - Important Details in Performing and Interpreting the Scratch Collapse Test.
AB  - : The utility of the scratch collapse test has been demonstrated in examination
      of patients with carpal and cubital tunnel syndromes and long thoracic and
      peroneal nerve compressions. In the authors' clinic, this lesser known test plays
      a key role in peripheral nerve examination where localization of the nerve
      irritation or injury is not fully understood. Test utility and accuracy in
      patients with more challenging presentations likely correlate with tester
      understanding and experience. This article offers a clear outline of all stages
      of the test to improve interrater reliability. The nuances of test performance
      are described, including a description of situations where the scratch collapse
      test is deemed inappropriate. Four clinical scenarios where the scratch collapse
      test may be useful are included. Corresponding video content is provided to
      improve performance and interpretation of the scratch collapse test. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Diagnostic, V.

PMID- 29036023
TI  - Percutaneous Mesh Expansion: A Regenerative Wound Closure Alternative.
AB  - BACKGROUND: Puncture wounds in the 1-mm range usually heal without scars.
      Stacking rows of these punctures offers a scarless method to generate tissue by
      mesh expansion. The authors developed a percutaneous mesh expansion procedure and
      present their experience for its wound closure application. METHODS: Over a 6
      year period, the authors applied percutaneous mesh expansion to 65 consecutive
      patients aged 58 to 101 years (mean, 72 years) with 67 full-thickness calvarial
      defects ranging in size from 2.5 * 3 cm to 7 * 8 cm (mean, 14 cm) that would have
      all required flaps for closure. Thirty-six were still anticoagulated, and 20 had
      prior scalp resections. After tumescent epinephrine anesthesia, the authors
      temporarily approximate the wound by placing it under strong tension. Using 1.1
      mm cutting point needles that selectively sever tissues under tension, the
      authors inflict rows of staggered alternating punctures over a distance five
      times the defect width. This results in 20 percent expansion of the meshed area,
      generating the tissue necessary for defect coverage. When the tension is
      completely released, closure is performed with simple sutures or staples. The
      authors avoid overmeshing, especially close to the wound edges, and perform no
      undermining or additional incisions. RESULTS: At 6-week follow-up, all defects
      were healed with only a straight resection scar. However, of the 10 defects
      larger than 5 * 5 cm, five had wound healing delay and three required a small
      skin graft. No other complication was observed. CONCLUSIONS: Percutaneous mesh
      expansion is a minimally invasive procedure that harnesses the body's natural
      capabilities to regenerate across small gaps. It sums these regenerated gaps in a
      mesh pattern that expands tissues to close complex wounds without flaps or
      additional incisions. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 29036024
TI  - Minimally Invasive, Spring-Assisted Correction of Sagittal Suture Synostosis:
      Technique, Outcome, and Complications in 83 Cases.
AB  - BACKGROUND: This series describes the results of minimally invasive strip
      craniotomy with additional spring distraction. METHODS: Included are the first 83
      consecutive patients who underwent this procedure (January 1, 2010, to January 1,
      2014). Outcome parameters were collected prospectively and included surgical
      parameters and complications, the occurrence of papilledema, skull growth,
      cephalic index, and photographic scores. RESULTS: Duration of surgery was 63
      minutes, 19 percent required blood transfusion, and complications were minor.
      Postoperative papilledema occurred in two patients (2.4 percent). Head growth
      increased after insertion of the springs and declined afterward to 0.7 SD,
      comparable to earlier cohorts in the authors' center. The cephalic index
      increased from 67 before surgery to 74 after surgery and showed a small decrease
      during the 4-year follow-up. Photographic scores confirmed the initial
      improvement and showed a trend to further improvement during follow-up.
      CONCLUSIONS: In this cohort, spring-assisted, minimally invasive strip craniotomy
      was safe and effective. Results were similar to those from other techniques but
      with smaller incisions, shorter interventions, reduced blood loss, and a lower
      incidence of postoperative papilledema. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 29036025
TI  - The Fate of the Adipose-Derived Stromal Cells during Angiogenesis and
      Adipogenesis after Cell-Assisted Lipotransfer.
AB  - BACKGROUND: Cell-assisted lipotransfer is a process in which fat grafting is
      supplemented with autologous adipose-derived stromal cells. Since the efficacy of
      the technique was demonstrated, studies have focused on the mechanism by which
      cell-assisted lipotransfer enhances the rate of graft survival. However, the
      microenvironmental changes in donor and recipient tissue associated with cell
      assisted lipotransfer remain unclear. METHODS: The authors introduced an animal
      model of cell-assisted lipotransfer using two different transgenic reporter mice.
      Donor fat from green fluorescent protein-expressing C57BL/6J mice and donor
      adipose-derived stromal cells from DsRed-expressing C57BL/6J mice were co
      transplanted into recipient C57BL/6J mice. During adipose remodeling after cell
      assisted lipotransfer, the fate of each donor adipocyte and donor adipose-derived
      stromal cell was traced using immunofluorescent staining with the whole-mount
      method. RESULTS: Adipose-derived stromal cell supplementation altered
      inflammation and promoted angiogenesis and subsequent revascularization in
      recipient tissue. Tracing at postoperative week 4 revealed that surviving donor
      adipose-derived stromal cells participated in angiogenesis by differentiating
      into endothelial cells. Moreover, newly differentiated fat from donor adipose
      derived stromal cells and recipient tissue integrated with surviving donor fat,
      leading to improved retention of the graft. Adipose-derived stromal cell
      supplementation resulted in a quantitative difference in angiogenesis and
      adipogenesis during adipose remodeling according to the concentration of adipose
      derived stromal cells. CONCLUSIONS: The authors characterized the dynamic changes
      occurring in donor adipose-derived stromal cells and fat and recipient tissue by
      tracing these cellular components following cell-assisted lipotransfer. The
      authors' findings highlight the therapeutic value of cell-assisted lipotransfer
      in tissue transplantation.

PMID- 29036026
TI  - A Comparison of Functional Outcomes and Therapeutic Costs: Single-Digit
      Replantation versus Revision Amputation.
AB  - BACKGROUND: The functional outcomes and therapeutic costs between digit
      replantation and revision amputation have remained controversial. METHODS: A
      total of 1023 patients with single-digit traumatic amputation or
      devascularization who underwent successful digit replantation (failure excluded)
      or revision amputation from January 1, 2013, to January 1, 2016, were included in
      this study. All cases were subgrouped based on Tamai level of amputation and the
      injured digit. The clinical outcomes were assessed using the Michigan Hand
      Outcomes Questionnaire 1 year after the initial operation. The authors also
      compared the cost of treatment, the duration of hospitalization, and the duration
      of sick leave between the two treatments. RESULTS: Replantation of small (level I
      to V), ring (level I to III), and long (level I) fingers showed no functional
      benefit compared with initial revision amputation. In contrast, replantation of
      thumb (level I to V), index (level I to V), long (level II to V), and ring (level
      IV to V) fingers had better outcomes. The cost of replantation was higher and the
      durations of hospitalization and sick leave of replantation were also longer
      compared with the revision amputation group. CONCLUSIONS: Single amputated
      injuries of small (level I to V), ring (level I to III), and long (level I)
      fingers are a relative contradiction for replantation. Replantation of thumb
      (level I to V), index (level I to V), long (level II to V), and ring (level IV to
      V) fingers showed extra benefit compared with revision amputation.

PMID- 29036027
TI  - Early Macrophage Infiltration Improves Fat Graft Survival by Inducing
      Angiogenesis and Hematopoietic Stem Cell Recruitment.
AB  - BACKGROUND: Fat grafting is a popular soft-tissue filler method; however, its
      results are variable and technique-dependent. Macrophages are present in fat
      grafts and closely associated with tissue regeneration. The authors hypothesized
      that activation/depletion of early macrophages in transferred fat
      improves/impairs fat graft survival. METHODS: Mouse inguinal fat (approximately
      150 mg) was transferred autologously. Fat grafting was first performed without
      other manipulations to obtain baseline information. Then, liposome-encapsulated
      clodronate and macrophage-colony stimulating factor were used in a mouse fat
      grafting model for local macrophage depletion or activation. The authors examined
      the graft stromal vascular fraction by fluorescence-activated cell sorting at 1,
      2, 4, and 12 weeks after transplantation in manipulation and control groups.
      Graft weight, vascularization, and secreted factors were also compared. RESULTS:
      Early depletion of macrophages resulted in incompetent angiogenesis, feeble Sca
      1/CD45 stem cell recruitment, and eventually a poor retention rate (34 +/- 6 mg
      versus control 84 +/- 15 mg; p = 0.006), whereas up-regulated macrophages allowed
      better angiogenesis and survival (117 +/- 12 mg versus control, 84 +/- 15 mg; p =
      0.043). CONCLUSIONS: In fat grafting, macrophages and their polarization
      initiated changes in the levels of dominant secreted factors and influenced blood
      derived stem cell infiltration, indicating that macrophages were crucial for
      tissue revascularization. The macrophage manipulation models described here show
      that graft macrophage number can profoundly influence graft survival.

PMID- 29036028
TI  - Appropriateness of the Use of Magnetic Resonance Imaging in the Diagnosis and
      Treatment of Wrist Soft Tissue Injury.
AB  - BACKGROUND: When diagnosing wrist soft tissue injury, the authors hypothesize
      that magnetic resonance imaging is used injudiciously and is associated with
      unnecessary cost. METHODS: A retrospective review was conducted of patients aged
      20 to 60 years who underwent magnetic resonance imaging for possible wrist soft
      tissue injury at a tertiary care center between 2009 and 2014. Treatment
      recommendation was classified as nonoperative, operative, or equivocal. If the
      magnetic resonance imaging-directed treatment recommendation differed from the
      pre-imaging recommendation, it was noted that the imaging influenced patient care
      (impact study). The cost estimate of an impact study was calculated by dividing
      the total studies performed by the number of studies that impacted the treatment
      recommendation and multiplying this value by the institutional wrist magnetic
      resonance imaging cost ($2246 in 2016). RESULTS: One hundred forty patients were
      included. Magnetic resonance imaging affected treatment recommendation in 28
      percent of patients. Independent predictors of impact on treatment recommendation
      were "question specific injury" (OR, 9.46; 95 percent CI, 3.18 to 28.16; p <
      0.001) and "question scapholunate injury" (OR, 2.88; 95 percent CI, 1.21 to 6.88;
      p = 0.02). The only independent predictor of surgery was ordering physician (hand
      surgeon) (OR, 3.69; 95 percent CI, 1.34 to 10.13; p = 0.01). The cost of an
      impact study ordered by a non-hand surgeon versus a hand surgeon was $13,359
      versus $6491, respectively. CONCLUSIONS: The provider must carefully consider the
      pretest probability of ordering a study that will affect treatment
      recommendation. Injudicious screening with magnetic resonance imaging ($15,565)
      incurred a cost nearly seven times the cost of the one imaging scan ($2246)
      before impacting one treatment recommendation. In the current era of cost
      containment and bundled payment, diagnostic test probability must be appreciated
      to guide physician ordering practices.

PMID- 29036029
TI  - Anterior Skull Base and Pericranial Flap Ossification after Frontofacial Monobloc
      Advancement.
AB  - BACKGROUND: Frontofacial monobloc advancement creates a communication between the
      anterior cranial fossa and nasal cavities. To tackle this issue, transorbital
      pericranial pedicled flaps are routinely performed in the authors' center. This
      study aimed to assess the postoperative ossification of the anterior skull base
      and pedicled flaps following frontofacial monobloc advancement, and to identify
      factors influencing this ossification. METHODS: Measurements of the skull base
      only and of the ossified pedicled flaps together with the skull base were
      performed on computed tomographic scans at the nasofrontal and the nasoethmoid
      frontal junctions. The total thickness of the skull vault was measured and a
      qualitative defect score for the anterior skull base was computed. RESULTS:
      Twenty-two patients who underwent frontofacial monobloc advancement at a median
      age of 3.1 years (range, 1.9 to 3.6 years) were included: 14 with Crouzon, five
      with Pfeiffer, and three with Apert syndrome. One year and 5 years after surgery,
      the distraction gap was completely ossified in the anterior skull base midline in
      all patients. Ossified pedicled flaps together with the skull base were thicker
      in patients than in controls at these two time points (p < 0.005 and p < 0.02).
      Patients with Pfeiffer syndrome had a significantly thicker skull base only and
      ossified pedicled flaps together with the skull base thicknesses (p = 0.01 and p
      = 0.03) and lower defect scores than patients with Crouzon or Apert syndrome (p =
      0.03) 1 year postoperatively. CONCLUSION: As ossification of the pedicled flaps
      and total reossification of the anterior skull base midline were observed in all
      patients, the authors indicate that performing pedicled flaps in frontofacial
      monobloc advancement surgery could promote the reossification of the anterior
      skull base. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 29036030
TI  - What's New in Shock, November 2017?

PMID- 29036031
TI  - Value of the Delta Neutrophil Index for Predicting 28-Day Mortality in Patients
      With Acute Pulmonary Embolism in the Emergency Department.
AB  - PURPOSE: Acute pulmonary embolism (PE), frequently seen in the emergency
      department (ED), is a leading cause of cardiovascular morbidity and mortality.
      The delta neutrophil index (DNI) reflects the fraction of circulating immature
      granulocytes as a component of the systemic inflammatory response syndrome
      criteria. The pathogenesis of acute PE is significantly associated with
      inflammation. The aim of the study was to investigate the clinical usefulness of
      the DNI as a marker of severity in patients with acute PE admitted to the ED.
      METHODS: We retrospectively analyzed the data of patients who were diagnosed with
      acute PE at a single ED, admitted from January 1, 2011 to June 30, 2017. The
      diagnosis of acute pulmonary embolism was confirmed using clinical, laboratory,
      and radiological findings. The DNI was determined at presentation. The clinical
      outcome was all-cause mortality within 28 days of emergency department admission.
      RESULTS: We included 447 patients in this study. The multivariate Cox regression
      model demonstrated that higher DNI values on ED admission were significantly
      associated with short-term mortality (hazard ratio, 1.107; 95% confidence
      interval, 1.042-1.177). The optimal cut-off DNI value, measured on ED admission,
      was 3.0%; this value was associated with an increased hazard of 28-day mortality
      following PE (HR, 7.447; 95% CI, 4.183-13.366; P < 0.001) CONCLUSION:: The DNI
      value, obtained as part of the complete blood count analysis, can be easily
      determined without additional burdens of cost or time. A high DNI is useful as a
      marker to predict 28-day mortality in patients with acute PE.

PMID- 29036033
TI  - Incidence of Nodal Metastasis and Isolated Aortic Metastases in Patients with
      Surgically Staged Endometrioid Endometrial Cancer: Erratum.

PMID- 29036032
TI  - A Physiological Profile of Ovarian Cancer Survivors to Inform Tailored Exercise
      Interventions and the Development of Exercise Oncology Guidelines.
AB  - OBJECTIVE: Physical activity has become increasingly important in supportive
      cancer care. However, physical activity and exercise guidelines for ovarian
      cancer survivors remain generic. The aim of this narrative review is to summarize
      existing data regarding the physiological characteristics (treatment-related
      adverse effects, concurrent comorbidities, body weight and composition, physical
      fitness and function, and physical activity behavior) of ovarian cancer survivors
      to further understanding of their cancer-specific physical activity and exercise
      needs. We also highlight gaps in the current knowledge base. METHODS: We
      undertook a narrative review of current literature on the physiological status of
      ovarian cancer survivors. We defined physiological status as treatment-related
      adverse effects, concurrent comorbidities, body weight and composition, physical
      fitness and function, and physical activity behavior. RESULTS: In addition to
      disease- and treatment-related symptoms and adverse effects, the majority of
      ovarian cancer survivors have comorbidities, which may adversely affect treatment
      effectiveness and safety, as well as survival. Despite high overweight and
      obesity rates, a large percentage of women are malnourished at diagnosis, with
      potentially compromised muscle mass and muscle density. Low muscle density at
      diagnosis and loss of muscle mass during treatment may be associated with worse
      survival outcomes. A small number of studies have observed impaired physical
      function and cardiorespiratory fitness in ovarian cancer survivors. The majority
      of ovarian cancer survivors are insufficiently active or sedentary. CONCLUSIONS:
      Our review suggests that ovarian cancer survivors could benefit from physical
      activity and exercise oncology interventions aimed at addressing detrimental
      changes to physiological status due to disease and treatment. However, current
      knowledge gaps regarding the physiological characteristics of ovarian cancer
      survivors throughout the entire survivorship spectrum challenge the development
      of tailored exercise intervention studies and exercise oncology guidelines.

PMID- 29036034
TI  - Investigation of Association Between Borderline Pancreatic Head Cancer and
      Glucose Uptake by Using Positron-Emission Tomographic Studies.
AB  - BACKGROUND In the background of the well-known importance of positron-emission
      tomographic studies (PET) in the prediction of pancreatic oncologic problems, we
      designed and performed this investigation to study the link between borderline
      pancreatic head cancer and glucose uptake by using PET. MATERIAL AND METHODS We
      retrospectively investigated patients during the period of almost 4 years (May
      2013 to December 2016). Patients underwent potentially curative resection for
      borderline exocrine pancreatic head adenocarcinoma without undergoing neoadjuvant
      therapy. We divided our PET protocol into 2 sets of methods as per renal calyces:
      1) U-RC type in which renal calyx (RC) has relatively higher value than that of
      18F-fluoro-2-deoxyglucose (18F-FDG) uptake and 2) S-RC type in which renal calyx
      has similar value than that of 18F-FDG uptake. RESULTS A total of 67 patients
      were enrolled after reclassification on the basis of majority-agreement. Among
      these patients, U-RC type was found in 22 patients (32.8%) while S-RC type was
      found in 45 patients (67.2%). Significant statistical differences were observed
      for each of the 2 types of pancreatic head cancer (U-RC type and S-RC type) in
      terms of adjusted cancer antigen 19-9 (CA 19-9), size of the tumor, tumor volume
      (TV2.8), maximum standard uptake value (SUV?), and lesion glycolysis (LG). A
      significantly longer disease-free survival time was shown by U-RC type (n=18)
      pancreatic cancer in comparison to S-RC type (n=42) (25.3 vs. 11.2 months).
      Additionally, U-RC type (n=4) had higher disease-free survival than did aS-RC
      type (n=3) (29.4 vs. 12.5 months). CONCLUSIONS Our PET protocol appears to be an
      indicator for estimation of recurrence of pancreatic head cancer and is as an
      indispensable asset to oncologists.

PMID- 29036035
TI  - The treatment path in hepatocellular carcinoma.
AB  - The treatment approach for hepatocellular carcinoma (HCC) depends on the stage
      and extent of disease, the severity of the underlying liver disease, and the
      overall performance status of the patient. Treatment consists of 4 main
      strategies: surgery (eg, resection and liver transplant), locoregional procedures
      (eg, ablation and transarterial embolization), systemic therapies, and best
      supportive care. For patients with early-stage tumors, surgical treatment or
      ablation can be curative. Patients with intermediate-stage disease can be
      candidates for embolization, administered as either transarterial
      chemoembolization (TACE) or transarterial radioembolization (TARE). Systemic
      therapy is reserved for patients with advanced or unresectable disease. For the
      past decade, the multitargeted kinase inhibitor sorafenib has been the only agent
      approved for unresectable HCC. This approval was followed by several clinical
      trials investigating other multitargeted kinase inhibitors, but none showed any
      benefit over single-agent sorafenib. Most patients progress after treatment with
      first-line sorafenib. In April 2017, the US Food and Drug Administration approved
      regorafenib for patients with HCC who have been previously treated with
      sorafenib. In a phase 3 trial, regorafenib significantly improved overall
      survival vs placebo. A consideration with systemic treatments is the proactive
      management of adverse events, including toxicities associated with the drugs and
      progression of liver disease.

PMID- 29036036
TI  - Advances in the management of hepatocellular carcinoma.

PMID- 29036037
TI  - Recent developments in systemic therapy for hepatocellular carcinoma.

PMID- 29036038
TI  - The evolving role of radioembolization in hepatocellular carcinoma.

PMID- 29036040
TI  - Frontline management of chronic lymphocytic leukemia.

PMID- 29036039
TI  - The treatment path in hepatocellular carcinoma: Further observations.

PMID- 29036042
TI  - Highlights in Lymphoma From the 2017 ASCO Meeting and the 14th ICML: Commentary.

PMID- 29036041
TI  - Highlights in Lymphoma From the 2017 American Society of Clinical Oncology Annual
      Meeting and the 14th International Conference on Malignant Lymphoma.

PMID- 29036043
TI  - Clarification and unification of the obliquity factor in diffraction and
      scattering theories: discussion.
AB  - Two-dimensional (2D) and three-dimensional (3D) diffraction theories form the
      underlying basis of quantitative phase imaging. This paper reviews how 2D and 3D
      diffraction theories are developed based on thin and thick object requirements.
      However, some previously reported work has mixed 2D and 3D theories. This
      discussion shows that it is possible to enable consistent mixed use of 2D and 3D
      theories by applying appropriate obliquity factor (OF) modifications. The
      discussion is concluded with an overall unifying representation for the usage of
      the OF modifications in 2D and 3D diffraction theories as applied to both thin
      and thick objects.

PMID- 29036044
TI  - Moire patterns of curved line quasi-periodic structures.
AB  - In this work, by using a local reciprocal vector concept, we introduce a
      considerable number of quasi-periodic structures where each of them is
      constructed by a set of curved lines with varying period. By using a simple and
      very comprehensive recently proposed method, formulations and characterizations
      of the various moire patterns of different pairs of curved line quasi-periodic
      structures are presented. Some advantages of the concept of local reciprocal
      vector in the area of curved line quasi-periodic structures are clarified.

PMID- 29036045
TI  - Long-term memory color investigation: culture effect and experimental setting
      factors.
AB  - Memory colors generated continuous interest in the color community. Previous
      studies focused on reflecting color chips and color samples in real scenes or on
      monitors. The cognitive effect of culture was rarely considered. In this paper,
      we performed a comprehensive investigation of the long-term memory colors of 26
      familiar objects using the asymmetric color matching method among Chinese and
      German observers on a display. Three experiments were conducted to evaluate the
      variations introduced by culture, context-based gray image, and initial matching
      color. Memory colors of important objects were collected and representative
      memory colors were quantified in terms of CIELAB L*, a*, and b* values. The intra
      and inter-observer variations were analyzed by mean-color-difference-from-mean
      values and chromatic ellipses. The effects of different cultural groups and
      experimental settings were also shown.

PMID- 29036046
TI  - Two-sided illumination in rigorous coupled-wave analysis applied to the 4pi
      microscope.
AB  - We apply the rigorous coupled-wave analysis (RCWA) to the simulation of 4pi
      microscopy. To achieve this, the concept of structured illumination [J. Opt. Soc.
      Am. A31, 2385 (2014)JOAOD60740-323210.1364/JOSAA.31.002385] is combined with the
      idea of coherent two-sided light incidence. We show how the latter can be
      integrated into the framework of the RCWA. Furthermore, we derive how light
      sources with different polarization types, such as linear, radial, or azimuthal
      polarization, can be realized in a general form. We combine these techniques to
      simulate two coherent counterpropagating converging beams incident upon a sample,
      as in 4pi-microscopy.

PMID- 29036047
TI  - Integral imaging techniques for flexible sensing through image-based
      reprojection.
AB  - In this work, a 3D reconstruction approach for flexible sensing inspired by
      integral imaging techniques is proposed. This method allows the application of
      different integral imaging techniques, such as generating a depth map or the
      reconstruction of images on a certain 3D plane of the scene that were taken with
      a set of cameras located at unknown and arbitrary positions and orientations. By
      means of a photo-consistency measure proposed in this work, all-in-focus images
      can also be generated by projecting the points of the 3D plane into the sensor
      planes of the cameras and thereby capturing the associated RGB values. The
      proposed method obtains consistent results in real scenes with different surfaces
      of objects as well as changes in texture and lighting.

PMID- 29036048
TI  - Laser diode side-pumped Nd:YVO4 microchip laser with film-etched microcavity
      mirrors.
AB  - Microchip lasers are applied as the light sources on various occasions with the
      end-pumping scheme. However, the vibration, the temperature drift, or the
      mechanical deformation of the pumping light in laser diodes in the end-pumping
      scheme will lead to instability in the microchip laser output, which causes
      errors and malfunctioning in the optic systems. In this paper, the side-pumping
      scheme is applied for improving the disturbance-resisting ability of the
      microchip laser. The transverse mode and the frequency purity of the laser output
      are tested. To ensure unicity in the frequency of the laser output, numerical
      simulations based on Fresnel-Kirchhoff diffraction theory are conducted on the
      parameters of the microchip laser cavity. Film-etching technique is applied to
      restrain the area of the film and form the microcavity mirrors. The laser output
      with microcavity mirrors is ensured to be in single frequency and with good beam
      quality, which is significant in the applications of microchip lasers as the
      light sources in optical systems.

PMID- 29036049
TI  - Partially coherent vortex beams of arbitrary order.
AB  - We derive analytic solutions for an infinite set of partially coherent vortex
      beams (PCVBs) of any azimuthal order and for any propagation distance. The
      correlation singularities of the beams and their orbital angular momentum are
      investigated. This detailed study of PCVBs opens the possibility of using such
      beams for remote sensing and free-space optical communications.

PMID- 29036050
TI  - Auto white balance by surface reflection decomposition.
AB  - Auto white balance (AWB) is an important operation in color imaging applications.
      Most existing AWB algorithms rely on some physical features and statistical
      properties of natural scenes. However, the AWB algorithms using statistical
      properties are sensitive to the statistics of the scene contents. Therefore, it
      is highly desirable to find physical features that are more robust and relatively
      insensitive to scene contents. In this paper, we propose such physical features
      based on surface reflection decomposition. Light reflection from most object
      surfaces can be decomposed into a specular component and a diffuse component.
      Instead of trying to find the common axis of the color planes as in past
      algorithms, we estimate the illuminant chromaticity by searching through the
      light source candidates to find the one that will best cancel the specular
      components. We provide two formulations: the minimum projected area algorithm and
      the minimum total variation algorithm for estimation of the scene-illuminant
      chromaticity. Both show very favorable results compared with other published
      algorithms.

PMID- 29036051
TI  - Combined measurement system for double shield tunnel boring machine guidance
      based on optical and visual methods.
AB  - In order to detect the position of the cutting shield at the head of a double
      shield tunnel boring machine (TBM) during the excavation, this paper develops a
      combined measurement system which is mainly composed of several optical feature
      points, a monocular vision sensor, a laser target sensor, and a total station.
      The different elements of the combined system are mounted on the TBM in suitable
      sequence, and the position of the cutting shield in the reference total station
      frame is determined by coordinate transformations. Subsequently, the structure of
      the feature points and matching technique for them are expounded, the position
      measurement method based on monocular vision is presented, and the calibration
      methods for the unknown relationships among different parts of the system are
      proposed. Finally, a set of experimental platforms to simulate the double shield
      TBM is established, and accuracy verification experiments are conducted.
      Experimental results show that the mean deviation of the system is 6.8 mm, which
      satisfies the requirements of double shield TBM guidance.

PMID- 29036052
TI  - Geometrical optics and optimal transport.
AB  - The Fermat principle is generalized to a system of rays. It is shown that all the
      ray mappings that are compatible with two given intensities of a monochromatic
      wave, measured at two planes, are stationary points of a canonical functional,
      which is the weighted average of the actions of all the rays. It is further shown
      that there exist at least two stationary points for this functional, implying
      that in the geometrical optics regime the phase from intensity problem has
      inherently more than one solution. The caustic structures of all the possible ray
      mappings are analyzed. A number of simulations illustrate the theoretical
      considerations.

PMID- 29036053
TI  - Complex Gaussian representations of partially coherent beams with nonconventional
      degrees of coherence.
AB  - We adopt the recently introduced complex Gaussian function to expand the
      partially coherent beams with nonconventional degrees of coherence, and derive
      detailed representations of Hermite-Gaussian correlated Schell-model beam,
      elliptical Laguerre-Gaussian correlated Schell-model beam, and multi-Gaussian
      correlated Schell-model beam. Complex Gaussian representation of a partially
      coherent beam provides a convenient way for treating its propagation. As an
      application example, we explore the self-splitting properties of a Hermite
      Gaussian correlated Schell-model beam propagating in a uniaxial crystal with the
      help of the complex Gaussian representation, and it is found that the uniaxial
      crystal can be used to control the splitting properties.

PMID- 29036054
TI  - Automated angular and translational tomographic alignment and application to
      phase-contrast imaging.
AB  - X-ray computerized tomography (CT) is a 3D imaging technique that makes use of x
      ray illumination and image reconstruction techniques to reproduce the internal
      cross-sections of a sample. Tomographic projection data usually require an
      initial relative alignment or knowledge of the exact object position and
      orientation with respect to the detector. As tomographic imaging reaches
      increasingly better resolution, thermal drifts, mechanical instabilities, and
      equipment limitations are becoming the main dominant factors contributing to
      sample positioning uncertainties that will further introduce reconstruction
      artifacts and limit the attained resolution in the final tomographic
      reconstruction. Alignment algorithms that require manual interaction impede data
      analysis with ever-increasing data acquisition rates, supplied by more brilliant
      sources. We present in this paper an iterative reconstruction algorithm for
      wrapped phase projection data and an alignment algorithm that automatically takes
      5 degrees of freedom, including the possible linear and angular motion errors,
      into consideration. The presented concepts are applied to simulated and real
      measured phase-contrast data, exhibiting a possible improvement in the
      reconstruction resolution. A MATLAB implementation is made publicly available and
      will allow robust analysis of large volumes of phase-contrast tomography data.

PMID- 29036055
TI  - New separated polynomial solutions to the Zernike system on the unit disk and
      interbasis expansion.
AB  - The differential equation proposed by Frits Zernike to obtain a basis of
      polynomial orthogonal solutions on the unit disk to classify wavefront
      aberrations in circular pupils is shown to have a set of new orthonormal solution
      bases involving Legendre and Gegenbauer polynomials in nonorthogonal coordinates,
      close to Cartesian ones. We find the overlaps between the original Zernike basis
      and a representative of the new set, which turn out to be Clebsch-Gordan
      coefficients.

PMID- 29036056
TI  - Coherent field propagation between tilted planes.
AB  - Propagating electromagnetic light fields between nonparallel planes is of special
      importance, e.g., within the design of novel computer-generated holograms or the
      simulation of optical systems. In contrast to the extensively discussed
      evaluation between parallel planes, the diffraction-based propagation of light
      onto a tilted plane is more burdensome, since discrete fast Fourier transforms
      cannot be applied directly. In this work, we propose a quasi-fast algorithm (O(N3
      log N)) that deals with this problem. Based on a proper decomposition into three
      rotations, the vectorial field distribution is calculated on a tilted plane using
      the spectrum of plane waves. The algorithm works on equidistant grids, so neither
      nonuniform Fourier transforms nor an explicit complex interpolation is necessary.
      The proposed algorithm is discussed in detail and applied to several examples of
      practical interest.

PMID- 29036057
TI  - Decomposition of the total wave aberration in generalized optical systems.
AB  - The increasing use of freeform optical surfaces raises the demand for optical
      design tools developed for generalized systems. In the design process, surface-by
      surface aberration contributions are of special interest. The expansion of the
      wave aberration function into field- and pupil-dependent coefficients is an
      analytical method used for that purpose. An alternative numerical approach
      utilizing data from the trace of multiple ray sets is proposed. The optical
      system is divided into segments of the optical path measured along the chief ray.
      Each segment covers one surface and the distance to the subsequent surface.
      Surface contributions represent the change of the wavefront that occurs due to
      propagation through individual segments. Further, the surface contributions are
      divided with respect to their phenomenological origin into intrinsic induced and
      transfer components. Each component is determined from a separate set of rays.
      The proposed method does not place any constraints on the system geometry or the
      aperture shape. However, here we concentrate on near-circular apertures and
      specify the resulting wavefront error maps using an expansion into Zernike
      polynomials.

PMID- 29036058
TI  - Nonrigid synthetic aperture radar and optical image coregistration by combining
      local rigid transformations using a Kohonen network.
AB  - This study proposes a new algorithm for nonrigid coregistration of synthetic
      aperture radar (SAR) and optical images. The proposed algorithm employs point
      features extracted by the binary robust invariant scalable keypoints algorithm
      and a new method called weighted bidirectional matching for initial
      correspondence. To refine false matches, we assume that the transformation
      between SAR and optical images is locally rigid. This property is used to refine
      false matches by assigning scores to matched pairs and clustering local rigid
      transformations using a two-layer Kohonen network. Finally, the thin plate spline
      algorithm and mutual information are used for nonrigid coregistration of SAR and
      optical images.

PMID- 29036059
TI  - Modeling astronomical adaptive optics performance with temporally filtered Wiener
      reconstruction of slope data.
AB  - We build on a long-standing tradition in astronomical adaptive optics (AO) of
      specifying performance metrics and error budgets using linear systems modeling in
      the spatial-frequency domain. Our goal is to provide a comprehensive tool for the
      calculation of error budgets in terms of residual temporally filtered phase power
      spectral densities and variances. In addition, the fast simulation of AO
      corrected point spread functions (PSFs) provided by this method can be used as
      inputs for simulations of science observations with next-generation instruments
      and telescopes, in particular to predict post-coronagraphic contrast improvements
      for planet finder systems. We extend the previous results presented in Correia
      and Teixeira [J. Opt. Soc. Am. A31, 2763 (2014)JOAOD60740
      323210.1364/JOSAA.31.002763] to the closed-loop case with predictive controllers
      and generalize the analytical modeling of Rigaut et al. [Proc. SPIE3353, 1038
      (1998)PSISDG0277-786X10.1117/12.321649], Flicker [Technical Report (W. M. Keck
      Observatory, 2007)], and Jolissaint [J. Eur. Opt. Soc.5, 10055 (2010)1990
      257310.2971/jeos.2010.10055]. We follow closely the developments of Ellerbroek
      [J. Opt. Soc. Am. A22, 310 (2005)JOAOD60740-323210.1364/JOSAA.22.000310] and
      propose the synthesis of a distributed Kalman filter to mitigate both aniso-servo
      lag and aliasing errors while minimizing the overall residual variance. We
      discuss applications to (i) analytic AO-corrected PSF modeling in the spatial
      frequency domain, (ii) post-coronagraphic contrast enhancement, (iii) filter
      optimization for real-time wavefront reconstruction, and (iv) PSF reconstruction
      from system telemetry. Under perfect knowledge of wind velocities, we show that
      ~60  nm rms error reduction can be achieved with the distributed Kalman filter
      embodying antialiasing reconstructors on 10 m class high-order AO systems,
      leading to contrast improvement factors of up to three orders of magnitude at few
      lambda/D separations (~1-5lambda/D) for a 0 magnitude star and reaching close to
      one order of magnitude for a 12 magnitude star.

PMID- 29036060
TI  - Wave optics simulations of synthetic aperture ladar performance through
      turbulence.
AB  - This paper utilizes a combination of theory and simulations to examine synthetic
      aperture imaging across a wide range of turbulence conditions. Extensive wave
      optics simulations are used to validate existing theory and to investigate the
      use of a common measurement technique. It demonstrates the applicability of
      earlier synthetic aperture laser radar (ladar) (SAL) research across a wide range
      of turbulence conditions, and examines the metric approaches and limitations for
      the imaging conditions normally seen in practical SAL systems. To examine the
      full impact of turbulence on SAL, the derivations, simulations, and analyses
      include three different resolution metrics as well as a commonly used contrast
      metric: the integrated sidelobe ratio. This paper demonstrates the integrated
      effects of turbulence on SAL imaging. Finally, suggestions are given for
      measuring the true resolving power of operational SAL systems.

PMID- 29036061
TI  - Wide-field spatiospectral interferometry: theory and imaging properties.
AB  - The emerging astronomical technique known as wide-field spatiospectral
      interferometry can provide hyperspectral images with spatial resolutions that are
      unattainable with a single monolithic-aperture observatory. The theoretical
      groundwork for operation and data measurement is presented in full detail,
      including relevant coherence theory. We also discuss a data processing technique
      for recovering a hyperspectral image from an interferometric data set as well as
      the unusual effective transfer function of the system.

PMID- 29036062
TI  - Vector polynomials for direct analysis of circular wavefront slope data.
AB  - In the aberration analysis of a circular wavefront, Zernike circle polynomials
      are used to obtain its wave aberration coefficients. To obtain these coefficients
      from the wavefront slope data, we need vector functions that are orthogonal to
      the gradients of the Zernike polynomials, and are irrotational so as to propagate
      minimum uncorrelated random noise from the data to the coefficients. In this
      paper, we derive such vector functions, which happen to be polynomials.

PMID- 29036064
TI  - Polarization properties of superposed vector Laguerre-Guassian beams during
      propagation.
AB  - We use analytical and numerical techniques to study the superposition of two
      vector Laguerre-Guassian (LG) beams. Vector LG beams contain rich polarization
      information and have many interesting intensity and polarization features. The
      composited electric field shows an inhomogeneous polarization distribution. We
      focus on looking for the distribution laws for the singularities obtained. The
      number and positions of singularity points are calculated and confirmed by
      numerical methods. We also study the fundamental cases for nonconcentric
      superposed vector LG beams and discover the difference distribution laws of
      several types of singular points in all the possible combinations.

PMID- 29036063
TI  - Illuminations that improve color discrimination ability of people with red-green
      color vision deficiency.
AB  - In this research, three illuminants that improve color discrimination ability of
      people with red-green color vision deficiency were developed. The illuminants are
      close to daylight-colored and were produced by using spectral optimization.
      Deutans were the focus of this research, but a few protans were also tested for
      reference. The illuminants were produced by combining different types of LEDs,
      and their effects were tested with several test subjects with and without color
      vision deficiency using the Ishihara color vision test and the Farnsworth Panel D
      15 test. The illuminant with the most powerful effect provided near perfect
      results with the Ishihara test for deutans, while the other two illuminants
      produced smaller improvements. The Farnsworth Panel D-15 test produced results
      that were similar to the Ishihara test though generally the color discrimination
      of blue hues was weaker under the most powerful illuminant.

PMID- 29036065
TI  - Electromagnetic energy stored in inhomogeneous scattering systems.
AB  - We analytically study the time-averaged electromagnetic energy stored inside
      scatterers containing inclusions of arbitrary shapes. Assuming the low density of
      inclusions, we derive the expression for the energy-transport velocity through
      disordered media without relying on the radiative transfer equation. Moreover,
      this expression is independent of the shape of scatterers. In addition, we obtain
      a relation between the dwell and absorption times associated with inclusions by
      considering the relationship between the internal energy and absorption cross
      section. An approximation for the electromagnetic energy stored inside a
      disordered medium in terms of the transport mean free path and the packing
      fraction is also derived. This expression suggests that the enhanced
      electromagnetic energy within the host medium is achieved for inclusions
      exhibiting negative scattering asymmetry parameters. As a result, disordered
      media with enhanced backscattering is expected to exhibit large quality factors.

PMID- 29036066
TI  - Analytical theory of real-argument Laguerre-Gaussian beams beyond the paraxial
      approximation.
AB  - We study the propagation of real-argument Laguerre-Gaussian beams beyond the
      paraxial approximation using the perturbation corrections to the complex-argument
      Laguerre-Gaussian beams derived earlier by Takenaka et al. [J. Opt. Soc. Am. A2,
      826 (1985)JOAOD60740-323210.1364/JOSAA.2.000826]. Each higher-order correction to
      the amplitude of the real-argument beam (l, m) is represented as a superposition
      of the same-order corrections to the amplitudes of the complex-argument beams (l,
      q) with q=0,1,2,...,m. We derive explicit expressions for the electric and
      magnetic fields of transversely and longitudinally polarized real-argument beams
      and calculate the chirality densities of these beams up to the fourth order of
      the smallness parameter. For the first time to the best of our knowledge, we show
      that essentially achiral Gaussian beams (corresponding to l=m=0) possess nonzero
      chirality density due to the wavefront curvature. The obtained corrections to the
      paraxial beams may prove useful for precise laser beam shaping and in studies of
      optomechanical forces.

PMID- 29036067
TI  - Analyzing visual-search observers using eye-tracking data for digital breast
      tomosynthesis images.
AB  - Visual-search (VS) model observers have the potential to provide reliable
      predictions of human-observer performance in detection-localization tasks. The
      purpose of this work was to examine some characteristics of human gaze on breast
      images with the goal of informing the design of our VS observers. Using a helmet
      mounted eye-tracking system, we recorded the movement of gaze from human
      observers as they searched for masses in sets of 2D digital breast tomosynthesis
      (DBT) images. The masses in this study were of a single profile. The DBT images
      were extracted from image volumes reconstructed with the filtered backprojection
      method. Fixation times associated with observer points of interest were computed
      from the observer data. We used the k-mean clustering algorithm to get dwell
      times of gaze data. The dwell times were then compared to sets of morphological
      feature values extracted from the images. These features, extracted as cross
      correlations involving the mass profile and the test image, included the matched
      filter (MF), gradient MF, Laplacian MF, and adaptive MF. The adaptive MF
      combining four feature maps was computed using a hotelling discriminant generated
      from training data. For this investigation, we computed correlation coefficients
      between the fixation times and the feature values. We also conducted a
      significance test by computing p-values of correlation coefficients for five
      features. Of all these features, the adaptive MF provided the highest correlation
      coefficients for DBT images with different densities.

PMID- 29036068
TI  - Critical object recognition in millimeter-wave images with robustness to rotation
      and scale.
AB  - Locating critical objects is crucial in various security applications and
      industries. For example, in security applications, such as in airports, these
      objects might be hidden or covered under shields or secret sheaths. Millimeter
      wave images can be utilized to discover and recognize the critical objects out of
      the hidden cases without any health risk due to their non-ionizing features.
      However, millimeter-wave images usually have waves in and around the detected
      objects, making object recognition difficult. Thus, regular image processing and
      classification methods cannot be used for these images and additional pre
      processings and classification methods should be introduced. This paper proposes
      a novel pre-processing method for canceling rotation and scale using principal
      component analysis. In addition, a two-layer classification method is introduced
      and utilized for recognition. Moreover, a large dataset of millimeter-wave images
      is collected and created for experiments. Experimental results show that a
      typical classification method such as support vector machines can recognize 45.5%
      of a type of critical objects at 34.2% false alarm rate (FAR), which is a
      drastically poor recognition. The same method within the proposed recognition
      framework achieves 92.9% recognition rate at 0.43% FAR, which indicates a highly
      significant improvement. The significant contribution of this work is to
      introduce a new method for analyzing millimeter-wave images based on machine
      vision and learning approaches, which is not yet widely noted in the field of
      millimeter-wave image analysis.

PMID- 29036069
TI  - Human detection in occluded scenes through optically inspired multi-camera image
      fusion.
AB  - In this paper, a novel approach for foreground extraction has been proposed based
      on a popular three-dimensional imaging technique in optics, called integral
      imaging. In this approach, multiple viewpoint images captured from a three
      dimensional scene are used to extract range information of the scene and
      effectively extract an object or a person, even in the presence of heavy
      occlusion. The algorithm consists of two parts: depth estimation and
      reconstruction of the targeted object at the estimated depth distance. Further
      processing of the resulting reconstructed image can lead to the detection of a
      face or a pedestrian in the scene, which may not otherwise be detectable due to
      partial occlusion in each of the views. The validity of our approach has been
      demonstrated by experimental results in different scenarios.

PMID- 29036070
TI  - Improvement of contrast sensitivity with practice is not compatible with a
      sensory threshold account.
AB  - In forced-choice detection, incorrect responses are routinely ascribed to
      internal noise, because experienced psychophysical observers do not act as if
      they have a sensory threshold, below which all perceived intensities would be
      identical. To determine whether inexperienced observers have sensory thresholds,
      we examined psychometric functions (percent correct versus log contrast) for
      detection and detection in full-screen, dynamic visual noise. Over five days,
      neither type of psychometric function changed shape, but both shifted leftwards,
      indicating increased sensitivity. These results are not consistent with a lowered
      sensory threshold, which would decrease psychometric slope. Our results can be
      understood within the context of Dosher and Lu's "stochastic" perceptual template
      model [Vis. Res.40, 1269 (2000)], augmented to allow intrinsic uncertainty.
      Specifically, our results are consistent with a combination of reduced internal
      additive noise and improved filtering of external noise.

PMID- 29036071
TI  - Numerical stability of the C method and a perturbative preconditioning technique
      to improve convergence.
AB  - The translational coordinate transformation method (the C method) in grating
      theory is studied numerically and analytically. We first study the convergence
      characteristics of the C method by numerical computations in high floating-point
      data precisions. Guided by insights gained from this numerical study we
      analytically studied condition numbers of the most important eigenvalues of the
      eigenvalue problem of the C method. Asymptotic estimates of condition numbers of
      these eigenvalues and estimates of convergence rate of the error in satisfying
      the Helmholtz equation by the eigenvectors are derived. These theoretical results
      explain well many observed numerical phenomena of the C method. Using the first
      order perturbation theory of simple eigenvalues we analyze the effects of round
      off errors on eigenvalue distribution and condition numbers. This leads to an
      extremely simple perturbative preconditioning technique that significantly
      improves the numerical stability of the C method with as little as just one line
      of code modification. The performance of the perturbatively preconditioned C
      method is not inferior to the C method preconditioned by the multilinear
      parameterization technique. We recommend it as the preferred method for modeling
      deep and smooth gratings.

PMID- 29036072
TI  - Nonreciprocal waveguiding structures for THz region based on InSb.
AB  - We have studied theoretically and numerically surface magnetoplasmons in three
      types of THz guiding structures, namely, InSb/dielectric planar boundary,
      InSb/air/metal planar waveguide, and symmetric InSb/air/InSb planar waveguide, in
      the presence of an external magnetic field. We consider the Voigt magneto-optic
      configuration in which these structures provide a frequency range where only one
      propagation direction is allowed to support one-way propagation of the surface
      plasmon polariton, due to nonreciprocity of the structures. To study the
      dispersion properties associated with unidirectional propagation of
      magnetoplasmons in finite-size nanostructured waveguides, we have developed an
      efficient two-dimensional numerical technique based on the magneto-optic
      aperiodic rigorous coupled-wave analysis. We have shown that the one-way
      bandwidth can be controlled by an external magnetic field and by the permittivity
      and thickness of the dielectric guiding layer. To enable numerical simulation, we
      have utilized the configuration in which the magnetized section of a waveguide is
      along the direction of propagation sandwiched by the identical waveguide segments
      without a magnetic field. We have also shown that the one-way bandwidth can be
      controlled by an external magnetic field and by the permittivity and thickness of
      the dielectric guiding layer.

PMID- 29036073
TI  - Principles of image reconstruction in optical interferometry: tutorial.
AB  - This paper provides a general introduction to the problem of image reconstruction
      from interferometric data. A simple model of the interferometric observables is
      given, and the issues arising from sparse Fourier data are discussed. The effects
      of various regularizations are described. In the proposed general framework, most
      existing algorithms can be understood. For an astronomer, such an understanding
      is crucial not only for selecting and using an algorithm but also to ensure
      correct interpretation of the resulting image.

PMID- 29036074
TI  - Airplane wing deformation and flight flutter detection method by using three
      dimensional speckle image correlation technology.
AB  - Airplane wing deformation is an important element of aerodynamic characteristics,
      structure design, and fatigue analysis for aircraft manufacturing, as well as a
      main test content of certification regarding flutter for airplanes. This paper
      presents a novel real-time detection method for wing deformation and flight
      flutter detection by using three-dimensional speckle image correlation
      technology. Speckle patterns whose positions are determined through the vibration
      characteristic of the aircraft are coated on the wing; then the speckle patterns
      are imaged by CCD cameras which are mounted inside the aircraft cabin. In order
      to reduce the computation, a matching technique based on Geodetic Systems
      Incorporated coded points combined with the classical epipolar constraint is
      proposed, and a displacement vector map for the aircraft wing can be obtained
      through comparing the coordinates of speckle points before and after deformation.
      Finally, verification experiments containing static and dynamic tests by using an
      aircraft wing model demonstrate the accuracy and effectiveness of the proposed
      method.

PMID- 29036075
TI  - Extended Taylor frozen-flow hypothesis and statistics of optical phase in aero
      optics.
AB  - We present an extended Taylor frozen-flow model for the statistics of the
      spatiotemporal disturbances of the index of refraction of air and the phase of an
      optical beam propagated through the turbulent boundary and shear layers in a high
      Reynolds-number flow. By incorporating rapid random fluctuations of the flow
      velocity about a mean convection velocity and an anisotropic spatial power
      spectrum for the index of refraction, we calculate both the short-delay temporal
      structure function and the power spectral density of these disturbances. We
      discuss the predicted scaling behaviors for these quantities in the context of
      existing experimental observations, showing specifically the agreement of these
      predictions with some optical phase data obtained by the Airborne Aero-Optical
      Laboratory.

PMID- 29036076
TI  - Dual-wavelength polarimeter application in investigations of the optical activity
      of a langasite crystal.
AB  - A method of high-accuracy polarimetry, which includes optical activity
      measurements' systematic errors, was realized with a dual-wavelength polarimeter
      for the two wavelengths of 635 and 650 nm. Simultaneous measurements with
      neighboring wavelengths significantly improved the data processing by increasing
      the amount of obtained data to eliminate the systematic errors. For a langasite
      crystal, La3Ga5SiO14, we measured the temperature dependence of the gyration
      tensor component g11. Our acquired value does not exceed 0.47*10-5 and is much
      smaller than the previous results obtained by different experimental methods. The
      results presented in this paper are consistent with the calculated optical
      rotatory power from the crystal structure data and the polarizabilities of the
      atoms.

PMID- 29036077
TI  - Propagating Bloch bound states with orbital angular momentum above the light line
      in the array of dielectric spheres.
AB  - We present propagating Bloch bound states in the radiation continuum with orbital
      angular momentum in an infinite linear periodical array of dielectric spheres.
      The bound states in the continuum demonstrate a giant Poynting vector spiraling
      around the array. They can be excited by a plane wave with incident linear
      polarization with a small tilt relative to the axis of the array.

PMID- 29036078
TI  - Propagation properties of a partially coherent Lorentz beam in uniaxial crystal
      orthogonal to the optical axis.
AB  - The cross-spectral density function of a partially coherent Lorentz beam
      propagating in uniaxial crystal orthogonal to the optical axis is obtained, and
      the evolution properties and the spectral degree of coherence for a partially
      coherent Lorentz beam in uniaxial crystal are illustrated by using numerical
      examples. The influence of coherence length and the ratio of refractive index
      ne/no on the normalized intensity and spectral degree of coherence for a
      partially coherent Lorentz beam are analyzed in detail.

PMID- 29036079
TI  - Calculating corner singularities by boundary integral equations.
AB  - Accurate numerical solutions for electromagnetic fields near sharp corners and
      edges are important for nanophotonics applications that rely on strong near
      fields to enhance light-matter interactions. For cylindrical structures, the
      singularity exponents of electromagnetic fields near sharp edges can be solved
      analytically, but in general the actual fields can only be calculated
      numerically. In this paper, we use a boundary integral equation method to compute
      electromagnetic fields near sharp edges, and construct the leading terms in
      asymptotic expansions based on numerical solutions. Our integral equations are
      formulated for rescaled unknown functions to avoid unbounded field components,
      and are discretized with a graded mesh and properly chosen quadrature schemes.
      The numerically found singularity exponents agree well with the exact values in
      all the test cases presented here, indicating that the numerical solutions are
      accurate.

PMID- 29036080
TI  - Influence of polarization aberrations on point images.
AB  - In this paper, we derive Marechal-type approximations for the unpolarized imaging
      of points in the presence of small retardation and diattenuation. As the
      representation of such polarization aberrations is ambiguous in general, we show
      the independence of the results on choices and suggest modified definitions.

PMID- 29036081
TI  - Polynomial modal analysis of slanted lamellar gratings.
AB  - The problem of diffraction by slanted lamellar dielectric and metallic gratings
      in classical mounting is formulated as an eigenvalue eigenvector problem. The
      numerical solution is obtained by using the moment method with Legendre
      polynomials as expansion and test functions, which allows us to enforce in an
      exact manner the boundary conditions which determine the eigensolutions. Our
      method is successfully validated by comparison with other methods including in
      the case of highly slanted gratings.

PMID- 29036082
TI  - Binary classification of Mueller matrix images from an optimization of Poincare
      coordinates.
AB  - A new binary classification method for Mueller matrix images is presented which
      optimizes the polarization state analyzer (PSA) and the polarization state
      generator (PSG) using a statistical divergence between pixel values in two
      regions of an image. This optimization generalizes to multiple PSA/PSG pairs so
      that the classification performance as a function of number of polarimetric
      measurements can be considered. Optimizing PSA/PSG pairs gives insight into which
      polarimetric measurements are most useful for the binary classification. For
      example, in scenes with strong diattenuation, retardance, or depolarization
      certain PSA/PSG pairs would make two regions in an image look very similar and
      other pairs would make the regions look very different. The method presented in
      this paper provides a quantitative method for ensuring the images acquired can be
      classified optimally.

PMID- 29036083
TI  - Continuous digital zooming using local self-similarity-based super-resolution for
      an asymmetric dual camera system.
AB  - This paper presents a digital zooming method using a super-resolution (SR)
      algorithm based on the local self-similarity between the wide- and tele-view
      images acquired by an asymmetric dual camera system. The proposed SR algorithm
      consists of four steps: (i) registration of an optically zoomed image to the wide
      view image, (ii) restoration of the central region of the zoomed wide-view image,
      (iii) restoration of the boundary region of the zoomed wide-view image, and (iv)
      fusion of the results from steps (ii) and (iii). Since an asymmetric dual camera
      system acquires different-resolution images on the same scene due to the
      different optical specifications, the proposed method can restore the low
      resolution wide-view image using the ideal high-frequency component estimated
      from the optically zoomed image. Experimental results demonstrate that the
      proposed method can provide significantly improved high-resolution wide-view
      images compared to existing single-image-based SR methods.

PMID- 29036084
TI  - Temporal coherence of a low-power erbium-doped fiber laser with spectrally
      broadened output.
AB  - The temporal coherence of spectrally selected output from a CW broadband erbium
      doped fiber ring laser (EDFRL) based on four wave mixing is characterized using a
      fiber-optic Mach-Zehnder interferometer. The visibility is found to be comparable
      to that of a standard narrow-linewidth tunable laser when their spectral widths
      are matched using an intracavity filter in EDFRL. But its visibility is
      distinctly higher than two other broadband sources (superluminescent diode and
      amplified spontaneous source) even when their spectral widths are matched,
      establishing that the cavity effect aids the coherence in EDFRL by mitigating the
      phase noise from four wave mixing.

PMID- 29036085
TI  - Local receptive field constrained stacked sparse autoencoder for classification
      of hyperspectral images.
AB  - As a competitive machine learning algorithm, the stacked sparse autoencoder (SSA)
      has achieved outstanding popularity in exploiting high-level features for
      classification of hyperspectral images (HSIs). In general, in the SSA
      architecture, the nodes between adjacent layers are fully connected and need to
      be iteratively fine-tuned during the pretraining stage; however, the nodes of
      previous layers further away may be less likely to have a dense correlation to
      the given node of subsequent layers. Therefore, to reduce the classification
      error and increase the learning rate, this paper proposes the general framework
      of locally connected SSA; that is, the biologically inspired local receptive
      field (LRF) constrained SSA architecture is employed to simultaneously
      characterize the local correlations of spectral features and extract high-level
      feature representations of hyperspectral data. In addition, the appropriate
      receptive field constraint is concurrently updated by measuring the spatial
      distances from the neighbor nodes to the corresponding node. Finally, the
      efficient random forest classifier is cascaded to the last hidden layer of the
      SSA architecture as a benchmark classifier. Experimental results on two real HSI
      datasets demonstrate that the proposed hierarchical LRF constrained stacked
      sparse autoencoder and random forest (SSARF) provides encouraging results with
      respect to other contrastive methods, for instance, the improvements of overall
      accuracy in a range of 0.72%-10.87% for the Indian Pines dataset and 0.74%-7.90%
      for the Kennedy Space Center dataset; moreover, it generates lower running time
      compared with the result provided by similar SSARF based methodology.

PMID- 29036086
TI  - Deterministic mode representation of random stationary media for scattering
      problems.
AB  - Deterministic mode representation (DMR) is introduced for a three-dimensional
      random medium with a statistically stationary refractive index distribution. The
      DMR allows for the designing and fine tuning of novel random media by adjusting
      the weights of individual deterministic modes. To illustrate its usefulness, we
      have applied the decomposition to the problem of weak light scattering from a
      Gaussian Schell-model medium. In particular, we have shown how individual
      deterministic modes of the medium contribute to the scattered far-field spectral
      density distribution.

PMID- 29036087
TI  - Fast and accurate three-dimensional point spread function computation for
      fluorescence microscopy.
AB  - The point spread function (PSF) plays a fundamental role in fluorescence
      microscopy. A realistic and accurately calculated PSF model can significantly
      improve the performance in 3D deconvolution microscopy and also the localization
      accuracy in single-molecule microscopy. In this work, we propose a fast and
      accurate approximation of the Gibson-Lanni model, which has been shown to
      represent the PSF suitably under a variety of imaging conditions. We express the
      Kirchhoff's integral in this model as a linear combination of rescaled Bessel
      functions, thus providing an integral-free way for the calculation. The explicit
      approximation error in terms of parameters is given numerically. Experiments
      demonstrate that the proposed approach results in a significantly smaller
      computational time compared with current state-of-the-art techniques to achieve
      the same accuracy. This approach can also be extended to other microscopy PSF
      models.

PMID- 29036088
TI  - Interaction description of light propagation.
AB  - The interaction between real and virtual point emitters is presented as the
      propagation principle of light under arbitrary spatial coherence. It is supported
      on a geometrical interpretation of the two-point correlation and the introduction
      of the geometrical potential. This principle and the spectrum of classes of point
      emitters constitute a complete theoretical model that offers a unified
      phenomenological framework for interference and diffraction not only of light but
      also of single particles, which is not possible in the conventional formalism
      based on the wave superposition principle.

PMID- 29036089
TI  - Freeform aberrations in phase space: an example.
AB  - We consider how optical propagation and aberrations of freeform systems can be
      formulated in phase space. As an example system, a freeform prism is analyzed and
      discussed. Symmetry considerations and their group theory descriptions are given
      some importance. Numerical aberrations are also highlighted and put into the
      context of the underlying aberration theory.

PMID- 29036090
TI  - Optimal configuration of static Mueller imagers for target detection.
AB  - We investigate the target detection performance of static Mueller imagers that
      implement a fixed number of illumination and analysis polarization states. Using
      a maximin approach, we demonstrate that the optimal sets of measurement vectors
      consist in regular tetrahedra on the Poincare sphere and that, in this case, the
      obtained target/background contrast has a very simple expression. We then derive
      a universal lower bound on the contrast ratio between the best channel of a
      static imager and a fully adaptive one, and in a special case of practical
      interest, we demonstrate that this ratio is bounded and always larger than 1/9.
      This is very important in practice since static imagers are much easier to build
      and operate. Our results show that they constitute a good alternative where
      ultimate contrast improvement is not necessary.

PMID- 29036091
TI  - Large amplitude tip/tilt estimation by geometric diversity for multiple-aperture
      telescopes.
AB  - A novel method nicknamed ELASTIC is proposed for the alignment of multiple
      aperture telescopes, in particular segmented telescopes. It only needs the
      acquisition of two diversity images of an unresolved source, and is based on the
      computation of a modified, frequency-shifted, cross-spectrum. It provides a
      polychromatic large-range tip/tilt estimation with the existing hardware and an
      inexpensive noniterative unsupervised algorithm. Its performance is studied and
      optimized by means of simulations. They show that with 5000
      photoelectrons/subaperture/frame and 1024*1024 pixel images, residues are within
      the capture range of interferometric phasing algorithms such as phase diversity.
      The closed-loop alignment of a 6-subaperture mirror provides an experimental
      demonstration of the effectiveness of the method.

PMID- 29036092
TI  - Quantitative approach for defining basic color terms and color category best
      exemplars.
AB  - A new method is presented that identifies basic color terms (BCTs) from color
      naming data. A function is defined that measures how well a term is understood by
      a communicating population. BCTs are then separated from other color terms by a
      threshold value applied to this function. A new mathematical algorithm is
      proposed and analyzed for determining the best exemplar associated with each BCT.
      Using data provided by the World Color Survey, comparisons are made between the
      paper's methods and those from other studies. These comparisons show that the
      paper's new definition of "basicness" mostly agrees with the typical definition
      found in the color categorization literature, which was originally due to Kay and
      colleagues. The new definition, unlike the typical one, has the advantage of not
      relying on syntactic or semantic features of languages or color lexicons. This
      permits the methodology developed to be generalizable and applied to other
      category domains for which a construct of "basicness" could have an important
      role.

PMID- 29036093
TI  - Simulating real-world scenes viewed through ophthalmic lenses.
AB  - We present a comprehensive procedure to simulate real-world scenes viewed through
      ophthalmic lenses. Such a method enables us to anticipate the effects on image
      formation of the following combined undesired optical defects typically found in
      ophthalmic lenses: blur, distortion, and chromatic aberration. Additionally, it
      helps in comparing the expected scenes seen with different lens designs. The
      procedure is based on the following steps: (1) to calculate the distortion and
      local dioptric matrix associated with a set of different gaze directions; (2) to
      estimate point spread functions (PSF) associated with these matrices; (3) to
      compute the joint action of distortion, chromatic aberration, and PSF field on
      the scenes. We illustrate this procedure with two +5D spherical lenses: a
      moderately good performance lens and a highly degrading one. The method is
      suitable to evaluate ophthalmic lenses in a virtual reality framework.

PMID- 29036094
TI  - On the equivalence between Young's double-slit and crystal double-refraction
      interference experiments.
AB  - We show, both analytically and experimentally, that under common experimental
      conditions the interference pattern produced in a classic Young's double-slit
      experiment is indistinguishable from that generated by means of a doubly
      refracting uniaxial crystal whose optic axis makes a skew angle with the light
      propagation direction. The equivalence between diffraction and crystal optics
      interference experiments, taken for granted by Arago and Fresnel in their
      pioneering research on the interference of polarized light beams, is thus
      rigorously proven.

PMID- 29036095
TI  - 2D TM scattering problem for finite dielectric objects in a dielectric stratified
      medium employing Gabor frames in a domain integral equation.
AB  - We present a method to simulate two-dimensional scattering by dielectric objects
      embedded in a dielectric layered medium with transverse magnetic polarization
      through a domain integral equation formulation. A mixed spatial-spectral
      discretization is employed with both a spatial and a spectral representation
      along the direction of the layer interfaces. In the spectral domain, a
      discretization on a path through the complex plane is used on which the Green
      function is well behaved. To calculate the field-material interaction in the
      spatial domain, an auxiliary field is employed similar to the Li factorization
      rules. Numerical results show that this auxiliary-field formulation significantly
      improves accuracy, compared to a formulation that directly employs the electric
      field.

PMID- 29036096
TI  - Far-zone coherence changes of electromagnetic scattered field generated by an
      anisotropic particulate medium.
AB  - The far-zone scattered field generated by an anisotropic particulate medium with
      electromagnetic plane incident waves is discussed. The analytical expressions of
      the spectral density and spectral degree of coherence of the scattered field are
      derived, which show that the coherence properties of the scattered field depend
      on the characteristics of each particle and the distribution of particles. By
      simulations of two special cases, i.e., anisotropic random particles with
      isotropic determinate distribution and isotropic determinate particles with
      anisotropic random distribution, the properties of the medium and the
      polarization states of the incident wave play roles in the distribution of the
      spectral degree of coherence of the scattered field. Moreover, the general
      condition, anisotropic particles with anisotropic distribution, is briefly
      discussed. By comparing the results generated by different parameters, the
      coherence changes of scattered field are found in the scattered field.

PMID- 29036097
TI  - Quantitative phase imaging method based on an analytical nonparaxial partially
      coherent phase optical transfer function: erratum.
AB  - A correction is given for Eq. (8) in J. Opt. Soc. Am. A33, 2125 (2016)JOAOD60740
      323210.1364/JOSAA.33.002125.

PMID- 29036098
TI  - Numerical investigation of polarization filtering for direct optical imaging
      within scattering media.
AB  - We investigate the ability of polarization filtering to improve direct imaging of
      absorbing objects which are buried within scattering environments. We extend on
      previous empirical investigations by exploiting an efficient perturbation-based
      formalism, which is applicable to arbitrarily arranged sources and detectors with
      arbitrary polarizations. From this approach, we are able in some cases to find
      certain non-trivial linear combinations of polarization measurement channels that
      maximize the object resolution and visibility.

PMID- 29036099
TI  - Image formation in image scanning microscopy, including the case of two-photon
      excitation.
AB  - The effect of combining the image scanning microscopy (ISM) technique with two
      photon fluorescence microscopy is analyzed. The effective spatial frequency
      cutoff can be doubled, as compared with conventional two-photon fluorescence
      microscopy, and the magnitude of the optical transfer function near the cutoff of
      conventional two-photon microscopy is increased by orders of magnitude. For the
      two-photon case, it is found that the optimum pixel reassignment factor in ISM is
      not equal to one half, as is often assumed in single-photon fluoresence image
      scanning microscopy, because the excitation and detection point spread functions
      are different. The optimum reassignment factor depends on the noise level, and in
      general the useful cutoff spatial frequency is about 1.8 times that for
      conventional two-photon microscopy. The effect of altering the reassignment
      factor in single-photon fluorescence ISM with a Stokes shift is also
      investigated. Illumination using pupil filters, such as by a Bessel beam, is
      considered. Using a ring detector array is found to result in good imaging
      behavior, exhibiting a sharpening of the point spread function by a factor of 1.7
      compared with conventional fluorescence. Image formation in ISM can be considered
      in a four-dimensional spatial frequency space, giving new insight into the
      imaging properties. This approach is related to phase space representations such
      as the Wigner distribution function and the ambiguity function. A noniterative
      algorithm for image restoration is proposed.

PMID- 29036100
TI  - Short pulse laser beam beyond paraxial approximation.
AB  - Nonparaxial perturbative equations are derived from the scalar wave equation by
      taking into account spatiotemporal couplings. General solutions are obtained in
      Fourier space and further transformed back in direct space. They depend on
      parameters that can be used to match various boundary conditions and the
      perturbative expansion of any nonparaxial exact solutions. This parametrization
      is used to study the sensitivity of direct electron acceleration off an
      ultrashort tightly focused laser pulse to nonparaxial corrections of radially
      polarized electromagnetic fields.

PMID- 29036101
TI  - Classical ghost-imaging spectral ellipsometer.
AB  - We introduce a novel approach for the spectral characterization of inhomogeneous
      thin films and interfaces by means of an imaging ghost ellipsometer operating
      with classical light of Gaussian statistics. We show that the device output in
      general provides the ellipsometric information associated with the fractional
      Fourier transforms of the sample's reflection coefficients, which in special
      cases reduce to the Fourier transforms or images. The formalisms for both one
      dimensional and two-dimensional samples are presented. The method is insensitive
      to instrumentation errors and, unlike in traditional ellipsometry, no source or
      detector calibration is needed.

PMID- 29036102
TI  - Scattering of a Gaussian beam from a row of cylinders with rectangular cross
      section.
AB  - The transverse magnetic Gaussian beam diffraction from a finite number, equally
      spaced and rectangular cross section dielectric cylinder row is studied. The
      infinitely long cylinders' axes are perpendicular to the beam's direction of
      propagation. The cylinder row, with dielectric constant epsilonc=nc2, is treated
      as a periodic inhomogeneous film, with period ax and thickness wy, bounded by two
      semi-infinite homogeneous media. With this restriction, the method is valid only
      for square or rectangular cross section cylinders. The supercell and the plane
      wave expansion methods are used to calculate the eigenfrequencies and
      eigenvectors supported for a one-dimensional photonic crystal. Then, these
      eigenfrequencies and eigenvectors are used to expand the field in the
      inhomogeneous film. Numerical results are presented for ax greater than lambda
      (the incident light wavelength), wx (the cylinder width), and wg (Gaussian beam
      waist). Two cases are studied. In the first (second) case, the unit cell contains
      one cylinder (a cylinder row), which simulates the scattering from a single
      cylinder (an inhomogeneous thin film). The total integrated scattering in
      transmission (reflection) shows three well-defined minima (maxima), which are due
      to interference effects. Its positions can be approximately obtained with the
      formula lambdak=4ncwy/k, with k=3, 4, and 6. The total integrated scattering in
      transmission decreases linearly as a function of the cylinder number.

PMID- 29036103
TI  - Modeling the response of mesospheric sodium to pulsed-laser excitation.
AB  - A simulation modeling excitation of the sodium D2 line by nanosecond time scale
      pulsed lasers is described. By numerically integrating transition rates in the
      sodium hyperfine structure, the return flux per sodium atom is predicted as a
      function of laser power. The simulation should be useful for studies of
      mesospheric sodium and adaptive optics. Applications include the estimation of
      sodium column density from lidar return flux, and of laser guide star brightness
      for different pulsed laser formats. The simulation assumes that the pulse
      repetition frequency is sufficiently low (smaller than a few kilohertz) that
      atomic collisions restore local thermodynamic equilibrium between pulses. It is
      also assumed that the pulse length is short compared to the Larmor precession
      time scale. The numerical results are well-approximated by a simple analytic
      model for a three-level atom. The number of emitted photons is found to be
      primarily dependent on the product of the length of the laser pulse and the
      energy density.

PMID- 29036104
TI  - Orthogonality-breaking sensing model based on the instantaneous Stokes vector and
      the Mueller calculus: erratum.
AB  - For J. Opt. Soc. Am. A33, 434 (2016)JOAOD60740-323210.1364/JOSAA.33.000434, a
      corrected version of Eq. (9) is provided owing to typographical errors in the
      original article. The original full article text and calculations are unchanged.
      Another typo is corrected in Eq. (A5) of Appendix A.

PMID- 29036105
TI  - Focus engineering based on analytical formulae for tightly focused polarized
      beams with arbitrary geometric configurations of linear polarization.
AB  - Highly confined electromagnetic fields with controllable intensity profiles and
      polarization orientations are greatly desired in many fields. In this paper, we
      report on the generation of highly confined fields through tightly focused
      locally linearly polarized beams. Using the Richards-Wolf vectorial diffraction
      method, we derive and build integrated analytical formulae for calculating the
      tightly focused field of polarized beams with arbitrary geometric configurations
      of linear polarization. Based on the analytical model, the focusing properties of
      four types of polarized light beams, i.e., linearly, azimuthally, radially, and
      spatially variant polarized beams, with locally linear states of polarization are
      investigated numerically and discussed in detail. By manipulating the radial and
      azimuthal indices and initial phases, we obtain a tunable three-dimensional
      optical cage, multifoci, optical needles, and channels in the focal volume of a
      high-numerical-aperture objective lens. These peculiar properties may find
      applications in fields such as optical trapping and manipulation of nanoparticles
      and super-resolution microscopy imaging.

PMID- 29036106
TI  - Holographic imaging through a scattering layer using speckle interferometry.
AB  - Optical imaging through complex scattering media is one of the major technical
      challenges with important applications in many research fields, ranging from
      biomedical imaging to astronomical telescopy to spatially multiplexed optical
      communications. Various approaches for imaging through a turbid layer have been
      recently proposed that exploit the advantage of object information encoded in
      correlations of the random optical fields. Here we propose and experimentally
      demonstrate an alternative approach for single-shot imaging of objects hidden
      behind an opaque scattering layer. The proposed technique relies on retrieving
      the interference fringes projected behind the scattering medium, which leads to
      complex field reconstruction, from far-field laser speckle interferometry with
      two-point intensity correlation measurement. We demonstrate that under suitable
      conditions, it is possible to perform imaging to reconstruct the complex
      amplitude of objects situated at different depths.

PMID- 29036107
TI  - Infrared and visible image fusion via saliency analysis and local edge-preserving
      multi-scale decomposition.
AB  - To retain the details of a visible image with a discernible target area, we
      propose a multi-scale decomposition image fusion method based on a local edge
      preserving (LEP) filter and saliency detection. We first use a LEP filter to
      decompose the infrared and visible images. Then, a modified saliency detection
      method is utilized to detect the salient target areas of an infrared image, which
      determine the base layer's weights of fusion strategy. Finally, each layer is
      reconstructed to obtain a visually pleasing fused image. Comparison with 11 other
      state-of-the-art methods reveals the superiority of the proposed method in terms
      of quality and quantity results.

PMID- 29036108
TI  - Centralized inverse-Fano distribution for controlling conversion gain measurement
      accuracy of detector elements.
AB  - Statistical theory is applied to derive the centralized inverse-Fano distribution
      as a model for the probability distribution of the photon transfer conversion
      gain measurement for detector elements. This distribution is confirmed by
      experiment, thus supporting the theory and enhancing the credibility of the
      statistical model used. Analysis of the statistical distance between the derived
      functions and computationally fast approximate forms is carried out to determine
      the conditions when such approximations are useful. Theoretical results are then
      applied to develop algorithms for use in live experiments to calculate
      appropriate sample sizes for measuring the conversion gain given a user-specified
      acceptable uncertainty.

PMID- 29036109
TI  - Transparency in stereopsis: parallel encoding of overlapping depth planes.
AB  - We report that after extensive training, expert adults can accurately report the
      number, up to six, of transparent overlapping depth planes portrayed by brief
      (400 ms or 200 ms) random-element stereoscopic displays, and can well
      discriminate six from seven planes. Naive subjects did poorly above three planes.
      Displays contained seven rows of 12 randomly located *'s or +'s; jittering the
      disparities and number in each row to remove spurious cues had little effect on
      accuracy. Removing the central 3 degrees  of the 10 degrees  display to eliminate
      foveal vision hardly reduced the number of reportable planes. Experts could
      report how many of six planes contained +'s when the remainder contained *'s, and
      most learned to report up to six planes in reverse contrast (left eye white +'s;
      right eye black +'s). Long-term training allowed some experts to reach eight
      depth planes. Results suggest that adult stereoscopic vision can learn to
      distinguish the outputs of six or more statistically independent, contrast
      insensitive, narrowly tuned, asymmetric disparity channels in parallel.

PMID- 29036110
TI  - Differential piston phase variance in non-Kolmogorov atmospheres.
AB  - We derive a generalized expression for the differential piston phase variance in
      non-Kolmogorov turbulence. Specifically, our result applies in the case where
      index of refraction is described by a power-law medium with an exponent between 0
      and 1. Kolmogorov assumptions of homogeneity and isotropy are maintained. After
      some development, our expression is derived using the Mellin-transform techniques
      and may be generalized to other forms for the three-dimensional index of
      refraction turbulence power spectrum. This analytical result has two regions of
      convergence. The separation between these regions is defined by a characteristic
      time given as the ratio of the mean wind speed and aperture size. By evaluating
      this expression, we find the differential piston phase variance exhibits a power
      law behavior roughly proportional to that of the medium. In addition, we find
      that piston phase variance decreases with increase in aperture size. We also find
      that the differential piston phase variance is independent of aperture size as
      the power law approaches unity.

PMID- 29036111
TI  - Self-focusing of a partially coherent beam with circular coherence.
AB  - In a recent publication [Opt. Lett.42, 1512 (2017)OPLEDP0146
      959210.1364/OL.42.001512], a novel class of partially coherent sources with
      circular coherence was introduced. In this paper, we examine the propagation
      behavior of the spectral density and the spectral degree of spatial coherence of
      a beam generated by such a source in free space and in oceanic turbulent media.
      It is found that the beam exhibits self-focusing, which is dependent on the
      initial coherence and the parameters of oceanic turbulence. The self-focusing
      phenomenon disappears when the initial coherence is high enough or the oceanic
      turbulence is strong. The area of high coherence appears in the center and along
      two diagonal lines. With increasing turbulence, the coherence area reduces
      gradually along one diagonal line and is retained along the other one. A physical
      interpretation of the self-focusing phenomenon is presented, and potential
      applications in optical underwater communication and beam shaping are considered.

PMID- 29036112
TI  - Improving color constancy by discounting the variation of camera spectral
      sensitivity.
AB  - It is an ill-posed problem to recover the true scene colors from a color biased
      image by discounting the effects of scene illuminant and camera spectral
      sensitivity (CSS) at the same time. Most color constancy (CC) models have been
      designed to first estimate the illuminant color, which is then removed from the
      color biased image to obtain an image taken under white light, without the
      explicit consideration of CSS effect on CC. This paper first studies the CSS
      effect on illuminant estimation arising in the inter-dataset-based CC (inter-CC),
      i.e., training a CC model on one dataset and then testing on another dataset
      captured by a distinct CSS. We show the clear degradation of existing CC models
      for inter-CC application. Then a simple way is proposed to overcome such
      degradation by first learning quickly a transform matrix between the two distinct
      CSSs (CSS-1 and CSS-2). The learned matrix is then used to convert the data
      (including the illuminant ground truth and the color-biased images) rendered
      under CSS-1 into CSS-2, and then train and apply the CC model on the color-biased
      images under CSS-2 without the need of burdensome acquiring of the training set
      under CSS-2. Extensive experiments on synthetic and real images show that our
      method can clearly improve the inter-CC performance for traditional CC
      algorithms. We suggest that, by taking the CSS effect into account, it is more
      likely to obtain the truly color constant images invariant to the changes of both
      illuminant and camera sensors.

PMID- 29036113
TI  - Far-zone behaviors of light waves on scattering from anisotropic quasi
      homogeneous media with semisoft boundaries.
AB  - A model of anisotropic quasi-homogeneous media with adjustable boundaries is
      presented with the help of the three-dimensional multi-Gaussian function. After
      that, the behaviors of the far-zone field of light waves on scattering from an
      anisotropic semisoft-boundary quasi-homogeneous medium are illustrated. It is
      shown that the spectral density of the scattered field is flattened-Gaussian
      centered, owing to the semisoft boundary of the scatterer, while the spectral
      degree of coherence is Gaussian-centered, which is independent of the boundary of
      scatterer. It is also shown that both the spectral density and the spectral
      degree of coherence are anisotropic because of the anisotropy of the scattering
      medium.

PMID- 29036114
TI  - Stochastic calculus analysis of optical time-of-flight range imaging and
      estimation of radial motion.
AB  - Time-of-flight range imaging is analyzed using stochastic calculus. Through a
      series of interpretations and simplifications, the stochastic model leads to two
      methods for estimating linear radial velocity: maximum likelihood estimation on
      the transition probability distribution between measurements, and a new method
      based on analyzing the measured correlation waveform and its first derivative.
      The methods are tested in a simulated motion experiment from (-40)-(+40)  m/s,
      with data from a camera imaging an object on a translation stage. In tests
      maximum likelihood is slow and unreliable, but when it works it estimates the
      linear velocity with standard deviation of 1 m/s or better. In comparison the new
      method is fast and reliable but works in a reduced velocity range of (-20)-(+20) 
      m/s with standard deviation ranging from 3.5 m/s to 10 m/s.

PMID- 29036115
TI  - Wide bandwidth, millimeter-resolution inverse synthetic aperture radar imaging.
AB  - The combination of wide bandwidth W-band inverse synthetic aperture radar imagery
      and high-fidelity numerical simulations has been used to identify distinguishing
      signatures from simple metallic and dielectric targets. Targets are located with
      millimeter-scale accuracy using super-resolution techniques. Radon transform
      reconstructions of the returns from rotated targets approached the image quality
      of the complete data set in a fraction of the time by sampling as few as 10
      angles. The limitations of shooting-and-bouncing ray simulations at high
      frequencies are illustrated through a critical comparison of their predictions
      with the measured data and the method of moments simulations, indicating the
      importance of accurately capturing the obfuscating role played by multipath
      interference in complex targets.

PMID- 29036116
TI  - Fast computer hologram generation by flexible-ratio adaptive point-spread
      spherical wave synthesis.
AB  - We propose a flexible-ratio adaptive point-spread spherical wave synthesis method
      for fast computer-generated hologram calculation. The conventional adaptive point
      spread algorithm uses a fixed ratio between the major and minor axes of the point
      source, whereas the proposed method uses flexible-ratio sources, i.e., ellipses,
      for more effective calculation. Numerical simulation was conducted to validate
      the proposed method. The results show that the proposed method has the potential
      to achieve faster calculation, compared to the calculation in conventional
      methods, without significant image degradation.

PMID- 29036117
TI  - Illuminant estimation in multispectral imaging.
AB  - With the advancement in sensor technology, the use of multispectral imaging is
      gaining wide popularity for computer vision applications. Multispectral imaging
      is used to achieve better discrimination between the radiance spectra, as
      compared to the color images. However, it is still sensitive to illumination
      changes. This study evaluates the potential evolution of illuminant estimation
      models from color to multispectral imaging. We first present a state of the art
      on computational color constancy and then extend a set of algorithms to use them
      in multispectral imaging. We investigate the influence of camera spectral
      sensitivities and the number of channels. Experiments are performed on
      simulations over hyperspectral data. The outcomes indicate that extension of
      computational color constancy algorithms from color to spectral gives promising
      results and may have the potential to lead towards efficient and stable
      representation across illuminants. However, this is highly dependent on spectral
      sensitivities and noise. We believe that the development of illuminant invariant
      multispectral imaging systems will be a key enabler for further use of this
      technology.

PMID- 29036119
TI  - Aberration analysis of AOTF-based spectral imaging systems.
AB  - Image aberrations caused by acousto-optic (AO) anisotropic diffraction in
      uniaxial crystals are discussed. For their analysis, we propose a simplified ray
      tracing model of an AO crystal cell (AOC). With this approach, one can assign any
      configuration of AO interaction, any material and geometry of the crystal, and
      then estimate all conventional ray aberrations, such as spherical, coma,
      astigmatism, distortion, etc. The optimization procedure is demonstrated by the
      aberration analysis of three principal spectral imaging schemes based on AO
      tunable filters (AOTFs). The approach developed promises performance improvement
      of AOTF-based systems for high-quality spectral imaging and image processing.

PMID- 29036118
TI  - Color opponency: tutorial.
AB  - In dialogue, two color scientists introduce the topic of color opponency, as seen
      from the viewpoints of color appearance (psychophysics) and measurement of nerve
      cell responses (physiology). Points of difference as well as points of
      convergence between these viewpoints are explained. Key experiments from the
      psychophysical and physiological literature are covered in detail to help readers
      from these two broad fields understand each other's work.

PMID- 29036120
TI  - Polarization-dependent effects of an Airy beam due to the spin-orbit coupling.
AB  - We investigate the polarization-dependent effects when a circularly polarized
      Airy beam propagates in an inhomogeneous medium. It shows that there are some
      interesting polarization-dependent phenomena induced by the spin-orbit coupling:
      the circularly polarized Airy beam will follow a polarization-dependent
      trajectory in an inhomogeneous medium, and there are the polarization-dependent
      self-acceleration of the Airy beam in the linear-index inhomogeneous medium and
      the polarization-dependent rotation of the Airy beam in the quadratic-index
      inhomogeneous medium. These polarization-dependent phenomena are different from
      the manifestation of the "traditional" spin Hall effect of a light beam, which
      just displays the polarization-dependent transverse deflection of the beam.

PMID- 29036121
TI  - Three-dimensional electromagnetic imaging of dielectric targets by means of the
      multiscaling inexact-Newton method.
AB  - A novel approach for three-dimensional electromagnetic imaging is presented. This
      technique is a combination of an iterative multiscaling approach with an inexact
      Newton method. The multiscaling procedure allows one to iteratively focus the
      region of interest on the detected target, whereas the inexact-Newton method
      provides an efficient regularized solution of the nonlinear electromagnetic
      inverse scattering problem for each scaling step. The proposed method is
      validated against numerical data with different configuration settings. A
      preliminary experimental validation is also reported.

PMID- 29036122
TI  - Wavefront spacing and Gouy phase in strongly focused fields: the role of
      polarization.
AB  - The wavefront spacings and the Gouy phases are investigated in the strongly
      focused fields with four differently polarized incident waves. It is shown that
      these four incident polarizations will lead to nine axial field components, which
      are found actually to only have five kinds of wavefront spacings and Gouy phases.
      The four analytical and one numerical expressions are derived for these five
      kinds of wavefront spacings in the immediate neighborhood of the focus. Our
      results show that the polarization state, the semiaperture angle, and beam size
      influence the wavefront spacings and the Gouy phases in different ways. The
      difference between two very near wavefront spacings can be bigger than a half
      wavelength. It is also found that the axial field components with the
      polarization states orthogonal to that of the incident wave always have larger
      wavefront spacings.

PMID- 29036123
TI  - Computational study of optical force between two nanodistant plasmonic
      submicrowires.
AB  - In this paper, the optical force between two circular plasmonic wires of
      submicrometer diameter (0.3 MUm) with nanometer surface-to-surface distances (3
      30 nm) interacting with radiation of a complex point source (lambda~0.2 MUm) is
      numerically studied. Calculations (which are based on the Muller integral
      equations and the Maxwell stress tensor) show that an attractive optical force
      with a number of distinct peaks is created in distances 3-10 nm. However, for
      plasmonic-dielectric and plasmonic-reflector double-wires, the optical force has
      no such peaks. Comparisons reveal that the peaks are originated from the
      excitation of coupled surface plasmon polaritons in the gap region between the
      plasmonic wires.

PMID- 29036124
TI  - Generalization of differential ray tracing by automatic differentiation of
      computational graphs.
AB  - Optical design relies on ray tracing to evaluate and optimize the performance of
      optical systems. Differential ray tracing, in which the ray properties are
      calculated together with their derivatives, has been shown to be of interest to
      improve the accuracy and speed of common optical design tasks. We present in this
      paper an algorithm capable of performing differential ray tracing in the general
      case. This algorithm is not constrained by a specific optical system geometry
      such as rotational symmetry or restricted to a set of surface definitions (e.g.,
      conics, polynomial aspheres).

PMID- 29036125
TI  - Automatic classification of atherosclerotic tissue in intravascular optical
      coherence tomography images.
AB  - Intravascular optical coherence tomography (IVOCT) has been successfully utilized
      for in vivo diagnostics of coronary plaques. However, classification of
      atherosclerotic tissues is mainly performed manually by experienced experts,
      which is time-consuming and subjective. To overcome these limitations, an
      automatic method of segmentation and classification of IVOCT images is developed
      in this paper. The method is capable of detecting the plaque contour between the
      fibrous tissues and other components. Subsequently, the method classifies the
      tissues based on their texture features described by Fourier transform and
      discrete wavelet transform. The experimental results of 103 images show that an
      overall classification accuracy of over 80% in the indicator of depth and span
      angle is achieved in comparison to manual results. The validation suggests that
      this method is objective, accurate, and automatic without any manual
      intervention. The proposed method is able to demonstrate the artery wall
      morphology successfully, which is valuable for the research of atherosclerotic
      disease.

PMID- 29036126
TI  - General refraction problems with phase discontinuities on nonflat metasurfaces.
AB  - This paper provides a mathematical approach to study metasurfaces in nonflat
      geometries. Analytical conditions between the curvature of the surface and the
      set of refracted directions are introduced to guarantee the existence of phase
      discontinuities. The approach contains both the near and far field cases. A
      starting point is the formulation of a vector Snell's law in the presence of
      abrupt discontinuities on the interfaces.

PMID- 29036127
TI  - High-speed all-optical DNA local sequence alignment based on a three-dimensional
      artificial neural network.
AB  - This paper presents an optical processing approach for exploring a large number
      of genome sequences. Specifically, we propose an optical correlator for global
      alignment and an extended moire matching technique for local analysis of
      spatially coded DNA, whose output is fed to a novel three-dimensional artificial
      neural network for local DNA alignment. All-optical implementation of the
      proposed 3D artificial neural network is developed and its accuracy is verified
      in Zemax. Thanks to its parallel processing capability, the proposed structure
      performs local alignment of 4 million sequences of 150 base pairs in a few
      seconds, which is much faster than its electrical counterparts, such as the basic
      local alignment search tool.

PMID- 29036128
TI  - Modeling turbulence in underwater wireless optical communications based on Monte
      Carlo simulation.
AB  - Turbulence affects the performance of underwater wireless optical communications
      (UWOC). Although multiple scattering and absorption have been previously
      investigated by means of physical simulation models, still a physical simulation
      model is needed for UWOC with turbulence. In this paper, we propose a Monte Carlo
      simulation model for UWOC in turbulent oceanic clear water, which is far less
      computationally intensive than approaches based on computational fluid dynamics.
      The model is based on the variation of refractive index in a horizontal link.
      Results show that the proposed simulation model correctly reproduces lognormal
      probability density function of the received intensity for weak and moderate
      turbulence regimes. Results presented match well with experimental data reported
      for weak turbulence. Furthermore, scintillation index and turbulence-induced
      power loss versus link span are exhibited for different refractive index
      variations.

PMID- 29036129
TI  - Self-bending scalar and vector bottle sheets.
AB  - This work demonstrates the generation of auto-bending cylindrical/tubular Bessel
      Gauss bottle beams in homogeneous two-dimensional (2D) space. The corresponding
      wave fields flow through a two-dimensional curved trajectory leaving a
      singularity hollow central region, exhibiting the characteristic of circumventing
      obstacles. Scalar and vector fields are derived based on the angular spectrum
      decomposition method, the Helmholtz equation, the Lorenz gauge condition, and
      Maxwell's equations. The profile and area of the 2D bottle beams, together with
      the location of the autofocusing spots, are controlled by the intrinsic
      parameters of the illuminating waves and polarizations of the vector potential
      forming the incident fields. The demonstrated auto-bending cylindrical bottle
      beam solutions may find potential applications in acoustical and optical
      cloaking, auto-bending beam tweezers, imaging around steep corners, therapeutic
      investigations with unconventional autofocusing beams, acoustical and light
      sheets (i.e., slice of beams in 2D), and other related particle manipulation,
      isolation, and sorting devices, to name a few examples.

PMID- 29036130
TI  - Electromagnetic diffraction theory of refractive axicon lenses.
AB  - We study the field that is produced by a paraxial refractive axicon lens. The
      results from geometrical optics, scalar wave optics, and electromagnetic
      diffraction theory are compared. In particular, the axial intensity, the on-axis
      effective wavelength, the transverse intensity, and the far-zone field are
      examined. A rigorous electromagnetic diffraction analysis shows that the state of
      polarization of the incident beam strongly affects the transverse intensity
      distribution, but not the intensity distribution in the far zone.

PMID- 29036131
TI  - Response of quadrant detectors to structured beams via convolution integrals.
AB  - We propose a new expression for the response of a quadrant detector using
      convolution integrals. This expression, exploiting the properties of the
      convolution, is easier to evaluate by hand. Computationally, it is also
      practicable to use since a large number of computer programs can evaluate
      convolutions right away. We use the new expression to obtain an analytical form
      of the response of a quadrant detector for a Gaussian beam and for Hermite
      Gaussian beams in general. We compare this analytic expression for the response
      for the Gaussian beam with the approximations from previous studies and with the
      response obtained through simulations. From the response, we also obtained an
      analytical form for the sensitivity of the quadrant detector to a Gaussian beam.
      Lastly, we demonstrate the computational ease of using our new expression for the
      response by calculating the sensitivity of the quadrant detector to the Bessel
      beam.

PMID- 29036132
TI  - Description of deep saturated excitation multiphoton microscopy for super
      resolution imaging.
AB  - Here we recount the standard two-level model that describes saturated excitation
      (SAX) in multiphoton microscopy (MPM), a new technique for super-resolution
      fluorescence microscopy in scattering tissue, which requires no special chemistry
      and only simple modifications to a commercial MPM microscope. We use the model to
      study conditions required for improvements in MPM SAX resolution and experimental
      implementation strategies. Simulation results find zeros, or nodes, in the
      frequency response, which generate highly irregular point-spread functions
      (PSFs), such as rings and ripples, that contain spatial frequency content >3*
      larger than allowed by diffraction. These PSFs are a direct result of zeros in
      the frequency response of saturated fluorophores under specific excitation
      conditions. The impact on image quality is discussed using simulations of targets
      imaged with SAX PSFs. Further, we explore engineering sets of irregular PSFs by
      varying the excitation power and reconstructing super-resolution images from the
      set of captured images.

PMID- 29036133
TI  - Use of spectral sensitivity variability in reflectance recovery from colorimetric
      information.
AB  - There have been numerous methods for accessing the reflectance spectra; some
      methods enable one to obtain the spectra directly, such as using a
      spectrophotometer, hyper-spectral camera, and so forth. Even though the accuracy
      by which the spectra are obtained can be very high, the high price of these
      methods could pose an obstacle. On the other hand, there has been an interest in
      estimation of the spectral reflectance from colorimetric information that is more
      easily attainable; the accuracy in this case might not be as high but these
      methods are the most cost efficient. It is aimed, in this paper, to amalgamate
      the low price and high accuracy of the preceding approaches through relating
      spectral estimation to spectral sensitivity variability. The work is split into
      two major parts. The first part of the paper describes spectral sensitivity
      variability of humans and cameras in a theoretical manner and how it can be used
      in spectral recovery. In the second part, an attempt is made to extend the theory
      to real situations. At the end, it is shown how increasing the number of
      disparate colorimetric data of a specific object using the proposed methods aids
      in estimating spectral reflectance more accurately in a manner comparable to
      multi-spectral cameras.

PMID- 29036134
TI  - Refractive collimation beam shaper design and sensitivity analysis using a free
      form profile construction method.
AB  - A refractive laser beam shaper comprising two free-form profiles is presented.
      The profiles are designed using a free-form profile construction method such that
      each incident ray is directed in a certain user-specified direction or to a
      particular point on the target surface so as to achieve the required illumination
      distribution of the output beam. The validity of the proposed design method is
      demonstrated by means of ZEMAX simulations. The method is mathematically
      straightforward and easily implemented in computer code. It thus provides a
      convenient tool for the design and sensitivity analysis of laser beam shapers and
      similar optical components.

PMID- 29036135
TI  - Negative optical radiation force and spin torques on subwavelength prolate and
      oblate spheroids in fractional Bessel-Gauss pincers light-sheets.
AB  - Fractional Bessel-Gauss light-sheets [J. Opt.19, 055602 (2017)JOOPDB0150
      536X10.1088/2040-8986/aa649a], which correspond to finite optical "slices" in 2D
      and possess asymmetric slit openings and bending characteristics, are examined
      from the standpoint of optical radiation force and spin torque theories for a
      subwavelength spheroid with arbitrary orientation in space. The vector angular
      spectrum decomposition method in addition to the Lorenz gauge condition and
      Maxwell's equations are used to determine the Cartesian components of the
      incident radiated electric field of the Bessel-Gauss light-sheets. In the
      framework of the dipole approximation, the numerical results for the Cartesian
      components of the optical radiation force and spin torque vectors show that
      negative forces (oriented in the opposite direction of wave motion) and spin
      torques arise depending on the beam parameters, the orientation of the
      subwavelength spheroid in 3D space, and its aspect ratio (i.e., prolate versus
      oblate). The spin torque sign reversal reveals that counter-clockwise or
      clockwise rotations around the center of mass of the spheroid can occur. The
      results find important applications in the application of auto-focusing light
      sheets in particle manipulation, rotation, and optical sorting devices.

PMID- 29036136
TI  - Correlation-based evaluation of visual performance to reduce the statistical
      error of visual acuity.
AB  - Ophthalmologists evaluate visual acuity tests by the number of correctly
      recognized optotypes (usually letters) in the different lines of an eye chart.
      This probability-based scoring results in significant statistical error that can
      only be decreased by the time-consuming analysis of a larger number of optotypes.
      In this paper, we present a new, more precise correlation-based scoring method
      that takes the degree of misidentification into consideration too, rather than
      the mere fact of it. According to our experimental results, this new method
      decreases the uncertainty error by 28% if using the same number of optotypes at a
      given letter size or requires half the optotype number to produce the same error
      as that of probability-based scoring.

PMID- 29036137
TI  - Design of a broadband hemispherical wave collimator lens using the ray inserting
      method.
AB  - This paper presents a novel inhomogeneous hemispherical dielectric lens. The
      proposed lens is designed based on the ray inserting method (RIM). Applying this
      approach, a uniform distribution of the rays' end points over the lens plane
      aperture is achieved while lens matching to the environment refractive index is
      perfectly fulfilled. We can change the antenna features such as sidelobe level
      and gain by controlling the end point of each ray propagated through the
      hemispherical lens. The refractive index of the designed hemispherical
      inhomogeneous lens is derived and it is validated using COMSOL Multiphysics. The
      proposed lens is realized using material drilling and multilayer techniques.
      Analysis of the realized lens is performed using CST-Microwave Studio. The
      structure has been fabricated. The results of a simulation and experiment
      indicate good performances of realized planar lens in a wide frequency bandwidth.
      Comparing with other hemispherical lenses like classical half Maxwell fish-eye,
      the improvements in the gain, sidelobe levels, and input matching are achieved by
      using the RIM.

PMID- 29036138
TI  - Double distortion correction method in a catadioptric vision system with a conic
      mirror.
AB  - Because of the low calibration precision caused by reflector distortion in
      catadioptric vision systems with conic mirrors, we proposed a double distortion
      correction model based on the panoramic image rectification. The lens distortion
      and the reflector distortion are analyzed independently in the mathematic model
      of the double distortion correction. Moreover, the modified model in this paper
      added the trigonometric functions into the polynomial model to solve the combined
      distortion. Additionally, extensive experiments, both simulative and real data,
      have been carried out and show that the proposed model achieves comparable
      measurement accuracy in contrast with the traditional distortion method.

PMID- 29036139
TI  - Phase-error estimation and image reconstruction from digital-holography data
      using a Bayesian framework.
AB  - The estimation of phase errors from digital-holography data is critical for
      applications such as imaging or wavefront sensing. Conventional techniques
      require multiple i.i.d. data and perform poorly in the presence of high noise or
      large phase errors. In this paper, we propose a method to estimate isoplanatic
      phase errors from a single data realization. We develop a model-based iterative
      reconstruction algorithm that computes the maximum a posteriori estimate of the
      phase and the speckle-free object reflectance. Using simulated data, we show that
      the algorithm is robust against high noise and strong phase errors.

PMID- 29036140
TI  - Wavefronts, caustic, and intensity of a plane wave refracted by an arbitrary
      surface: the axicon and the plano spherical lenses.
AB  - The aim of the present work is to obtain an integral representation of the field
      associated with the refraction of a plane wave by an arbitrary surface. To this
      end, in the first part we consider two optical media with refraction indexes n1
      and n2 separated by an arbitrary interface, and we show that the optical path
      length, phi, associated with the evolution of the plane wave is a complete
      integral of the eikonal equation in the optical medium with refraction index n2.
      Then by using the k function procedure introduced by Stavroudis, we define a new
      complete integral, S, of the eikonal equation. We remark that both complete
      integrals in general do not provide the same information; however, they give the
      geometrical wavefronts, light rays, and the caustic associated with the
      refraction of the plane wave. In the second part, using the Fresnel-Kirchhoff
      diffraction formula and the complete integral, S, we obtain an integral
      representation for the field associated only with the refraction phenomena, the
      geometric field approximation, in terms of secondary plane waves and the k
      function introduced by Stavroudis in solving the problem from the geometrical
      optics point of view. We use the general results to compute: the wavefronts,
      light rays, caustic, and the intensity associated with the refraction of a plane
      wave by an axicon and plano-spherical lenses.

PMID- 29036141
TI  - Gloss evaluation from soft and hard metrologies.
AB  - Recent advances in bidirectional reflectance distribution function (BRDF)
      acquisitions have provided a novel approach for appearance measurement and
      analysis. In particular, since gloss appearance is dependent on the directional
      reflective properties of surfaces, it is reasonable to leverage the BRDF for
      gloss evaluation. In this paper, we investigate gloss appearance from both soft
      metrology and hard metrology. A psychophysical experiment was conducted for the
      gloss assessment of 47 neutral-color samples. In the evaluation of gloss
      perception from gloss meter measurements, we report several ambiguous
      correspondences in the medium gloss range. In order to analyze and explain this
      phenomenon, the BRDF was acquired and examined using a commercial BRDF measuring
      device. With an improved correlation-to-visual perception, we propose a two
      dimensional gloss model by combining a parameter, the standard deviation of the
      specular lobe, from Ward's BRDF model with measured gloss values.

PMID- 29036142
TI  - Standardized target-specific detectivity metric for computational imaging
      systems.
AB  - Multifunctional cameras capable of performing a wide variety of nearly
      simultaneous imaging tasks are expected to play a major role in the near future.
      Computational imaging (CI) systems will serve as one of the main enabling
      technologies for multifunctional cameras, especially due to the abundance of low
      cost, high-speed computational processing available today. An important aspect of
      these systems is to be able to quantify their performance with respect to
      specific imaging tasks. However, the non-traditional design of CI systems, both
      available and proposed, presents a considerable challenge to modeling, comparing,
      specifying, and measuring their performance. To solve this problem, this paper
      presents a standardized detection signal-to-noise ratio, referred to as a
      detectivity metric, along with a general CI system framework. This metric has the
      flexibility to handle various types of CI systems and specific targets while
      minimizing the complexity and assumptions needed. The detectivity metric is
      designed to assess the performance of a CI system searching for a specific known
      target or signal of interest. An analytical version of the detectivity metric is
      also presented for a compressive sensing CI system. Special considerations for
      standardization are also discussed.

PMID- 29036143
TI  - Complete confined bases for beam propagation in Cartesian coordinates.
AB  - Complete bases that are useful for beam propagation problems and present the
      distinct property of being spatially confined at the initial plane are proposed.
      These bases are constructed in terms of polynomials of Gaussians, in contrast
      with standard alternatives, such as the Hermite-Gaussian basis, that are given by
      a Gaussian times a polynomial. The property of spatial confinement implies that,
      for all basis elements, the spatial extent at the initial plane is roughly the
      same. This property leads to an optimal scaling parameter that is independent of
      truncation order for the fitting of a confined initial field. Given their form as
      combinations of Gaussians, the paraxial propagation of these basis elements can
      be modeled analytically.

PMID- 29036144
TI  - Second-order statistics of a radially polarized partially coherent twisted beam
      in a uniaxial crystal.
AB  - The Wigner function (WDF) has been used to study the second-order moments for a
      radially polarized partially coherent twisted (RPPCT) beam (i.e., a RPPC beam
      with a twist phase) propagating in a uniaxial crystal. With the help of the
      extended Huygens-Fresnel integral formula and definition of the WDF, the
      analytical formulas for propagation factor (M2-factor), effective radius of
      curvature (ERC), and Rayleigh range of a RPPCT beam propagating in a uniaxial
      crystal have been derived. Our numerical results show that the M2-factor of a
      RPPCT beam with larger absolute value of the twist factor or lower coherence is
      less affected by anisotropic diffraction in a uniaxial crystal. The dependence of
      the ERC and Rayleigh range of a RPPCT beam propagating in a uniaxial crystal on
      the parameter e along the x direction is much different from that along the y
      direction due to anisotropic diffraction. We can judge how much a RPPCT beam
      carries the twist factor by measuring the deviation percentage of the M2-factor
      of a RPPCT beam propagating in a uniaxial crystal and even can modulate the
      properties of a RPPCT beam by varying the beam parameters, which will be useful
      in some applications where a RPPCT beam is required.

PMID- 29036145
TI  - Computational integral field spectroscopy with diverse imaging.
AB  - Integral field spectroscopy (IFS) is a well-established method for measuring
      spectral intensity data of the form s(x,y,lambda), where x, y are spatial
      coordinates and lambda is the wavelength. In most flavors of IFS, there is a
      trade-off between sampling (x,y) and the measured wavelength band Deltalambda.
      Here we present the first, to our knowledge, attempt to overcome this trade-off
      by use of computational imaging and measurement diversity. We implement diversity
      by including a grating in our design, which allows rotation of the dispersed
      spectra between measurements. The raw intensity data captured from the rotated
      grating positions are then processed by an inverse algorithm that utilizes
      sparsity in the data. We present simulated results from spatial-spectral data in
      the experimental dataset. We used non-overlapping portions of the dataset to
      train our sparsity priors in the form of the dictionary, and to test the
      reconstruction quality. We found that, depending on the level of noise in the
      measurement, diversity up to a maximum number of measurements is beneficial in
      terms of reducing error, and yields diminishing returns if even more measurements
      are taken.

PMID- 29036146
TI  - Effects of a modulated vortex structure on the diffraction dynamics of ring Airy
      Gaussian beams.
AB  - The evolution of the ring Airy Gaussian beams with a modulated vortex in free
      space is numerically investigated. Compared with the unmodulated vortex, the
      unique property is that the beam spots first break up, and then gather. The
      evolution of the beams is influenced by the parameters of the vortex modulation,
      and the splitting phenomenon gets enhanced with multiple rings becoming light
      spots if the modulation depth increases. The symmetric branch pattern of the beam
      spots gets changed when the number of phase folds increases, and the initial
      modulation phase only impacts the angle of the beam spots. Moreover, a large
      distribution factor correlates to a hollow Gaussian vortex shape and weakens the
      splitting and gathering trend. By changing the initial parameters of the vortex
      modulation and the distribution factor, the peak intensity is greatly affected.
      In addition, the energy flow and the angular momentum are elucidated with the
      beam evolution features being confirmed.

PMID- 29036147
TI  - Basic properties and classification of Mueller matrices derived from their
      statistical definition.
AB  - Starting from the statistical definition of the Mueller matrix, we derive the
      relationships between basic properties, such as the number of contact points of
      the characteristic ellipsoid with the Poincare sphere and the rank of the
      covariance matrix. This approach enables the comprehensive classification of any
      experimental depolarizing Mueller matrix into one of six possible classes, thus
      making possible phenomenological interpretation in terms of a specific
      fluctuating Jones generator or of a finite sum of nondepolarizing Mueller
      matrices.

PMID- 29036148
TI  - Quasi-monochromatic modes of quasi-stationary, pulsed scalar optical fields.
AB  - We investigate the temporal coherence of random, pulsed, quasi-stationary scalar
      light fields and introduce a new type of expansion for the mutual coherence
      function in terms of fully coherent frequency-shifted quasi-monochromatic modes
      of identical shape. The mode representation is valid provided the pulse length is
      shorter and the coherence time is much shorter than the width of the time window
      in which the field is considered. The construction of the expansion is
      particularly straightforward since information is required only on the average
      spectrum and the average temporal intensity. The method enables us to assess the
      coherence properties of quasi-stationary light by analyzing the behavior of
      deterministic quasi-monochromatic fields. The frequency-domain counterpart of the
      representation is also given. The method is illustrated by application to a
      pulsed free-electron laser source.

PMID- 29036149
TI  - Bandwidth correction in the spectral measurement of light-emitting diodes.
AB  - Light-emitting diodes (LEDs) are widely employed in industrial applications and
      scientific research. However, spectral distortions will occur due to the
      broadening effects of the spectrometer when an LED spectrum is obtained with a
      spectrometer. In this paper, a novel approach is put forward to correct bandwidth
      for an LED spectrum based on a Levenberg-Marquardt algorithm and He-Zheng model.
      We compare estimation errors of different LED spectra by using the proposed
      method along with the Richardson-Lucy method and differential operator approach.
      The experimental results show that the effect of the proposed approach is better
      than that of the other two methods.

PMID- 29036150
TI  - Simple approach to the generalized Minkwitz theorem.
AB  - The Minkwitz theorem plays an important role in the design of progressive
      addition lenses. Recently, this theorem has been generalized by Esser et al. [J.
      Opt. Soc. Am. A34, 441 (2017)10.1364/JOSAA.34.000441JOAOD60740-3232] to non
      umbilic lines under the assumption of a symmetric surface. We present a
      simplified derivation and generalize their findings to arbitrary but sufficiently
      smooth surfaces.

PMID- 29036151
TI  - Automatic identification of fungi in microscopic leucorrhea images.
AB  - Identifying fungi in microscopic leucorrhea images provides important information
      for evaluating gynecological diseases. Subjective judgment and fatigue can
      greatly affect recognition accuracy. This paper proposes an automatic
      identification system to detect fungi in leucorrhea images that incorporates a
      convolutional neural network, the histogram of oriented gradients algorithm, and
      a binary support vector machine. In experiments, the detection rate of the
      positive samples was as high as 99.8%. The experimental results demonstrate the
      effectiveness of the proposed method and its potential as a primary software
      component of a completely automated system.

PMID- 29036152
TI  - Single freeform surface design for prescribed input wavefront and target
      irradiance.
AB  - In beam shaping applications, the minimization of the number of necessary optical
      elements for the beam shaping process can benefit the compactness of the optical
      system and reduce its cost. The single freeform surface design for input
      wavefronts, which are neither planar nor spherical, is therefore of interest. In
      this work, the design of single freeform surfaces for a given zero-etendue source
      and complex target irradiances is investigated. Hence, not only collimated input
      beams or point sources are assumed. Instead, a predefined input ray direction
      vector field and irradiance distribution on a source plane, which has to be
      redistributed by a single freeform surface to give the predefined target
      irradiance, is considered. To solve this design problem, a partial differential
      equation (PDE) or PDE system, respectively, for the unknown surface and its
      corresponding ray mapping is derived from energy conservation and the ray-tracing
      equations. In contrast to former PDE formulations of the single freeform design
      problem, the derived PDE of Monge-Ampere type is formulated for general zero
      etendue sources in Cartesian coordinates. The PDE system is discretized with
      finite differences, and the resulting nonlinear equation system is solved by a
      root-finding algorithm. The basis of the efficient solution of the PDE system
      builds the introduction of an initial iterate construction approach for a given
      input direction vector field, which uses optimal mass transport with a quadratic
      cost function. After a detailed description of the numerical algorithm, the
      efficiency of the design method is demonstrated by applying it to several design
      examples. This includes the redistribution of a collimated input beam beyond the
      paraxial approximation, the shaping of point source radiation, and the shaping of
      an astigmatic input wavefront into a complex target irradiance distribution.

PMID- 29036153
TI  - Fixed-pattern noise correction method based on improved moment matching for a TDI
      CMOS image sensor.
AB  - In this paper, an improved moment matching method based on a spatial correlation
      filter (SCF) and bilateral filter (BF) is proposed to correct the fixed-pattern
      noise (FPN) of a time-delay-integration CMOS image sensor (TDI-CIS). First, the
      values of row FPN (RFPN) and column FPN (CFPN) are estimated and added to the
      original image through SCF and BF, respectively. Then the filtered image will be
      processed by an improved moment matching method with a moving window.
      Experimental results based on a 128-stage TDI-CIS show that, after correcting the
      FPN in the image captured under uniform illumination, the standard deviation of
      row mean vector (SDRMV) decreases from 5.6761 LSB to 0.1948 LSB, while the
      standard deviation of the column mean vector (SDCMV) decreases from 15.2005 LSB
      to 13.1949LSB. In addition, for different images captured by different TDI-CISs,
      the average decrease of SDRMV and SDCMV is 5.4922/2.0357 LSB, respectively.
      Comparative experimental results indicate that the proposed method can
      effectively correct the FPNs of different TDI-CISs while maintaining image
      details without any auxiliary equipment.

PMID- 29036154
TI  - Perceptually optimized image rendering.
AB  - We develop a framework for rendering photographic images by directly optimizing
      their perceptual similarity to the original visual scene. Specifically, over the
      set of all images that can be rendered on a given display, we minimize the
      normalized Laplacian pyramid distance (NLPD), a measure of perceptual
      dissimilarity that is derived from a simple model of the early stages of the
      human visual system. When rendering images acquired with a higher dynamic range
      than that of the display, we find that the optimization boosts the contrast of
      low-contrast features without introducing significant artifacts, yielding results
      of comparable visual quality to current state-of-the-art methods, but without
      manual intervention or parameter adjustment. We also demonstrate the
      effectiveness of the framework for a variety of other display constraints,
      including limitations on minimum luminance (black point), mean luminance (as a
      proxy for energy consumption), and quantized luminance levels (halftoning). We
      show that the method may generally be used to enhance details and contrast, and,
      in particular, can be used on images degraded by optical scattering (e.g., fog).
      Finally, we demonstrate the necessity of each of the NLPD components-an initial
      power function, a multiscale transform, and local contrast gain control-in
      achieving these results and we show that NLPD is competitive with the current
      state-of-the-art image quality metrics.

PMID- 29036155
TI  - Condition for far-zone spectral isotropy of light radiated from a quasi
      homogeneous source scattering on a quasi-homogeneous random medium.
AB  - The far-zone spectral isotropy of light radiated from a secondary planar quasi
      homogeneous (QH) source scattering on a QH medium has been discussed. Without
      assuming the specified function of incident light, a sufficient condition for the
      far-zone spectral isotropy has been expressed as a new scaling law, which is
      analogous with the scaling law for weak scattering in previous works. Special
      examples are discussed to validate the obtained scaling law.

PMID- 29036156
TI  - Multifocus autofocusing Airy beam.
AB  - We propose a multifocus autofocusing Airy beam (MAAB) by modifying the frequency
      spectrum of a symmetric Airy beam (SAB) with a Gaussian band elimination filter.
      Unlike the original SAB, there are four off-axis foci at the autofocusing plane
      of the MAAB. The MAAB has a better abruptly autofocusing property than the
      original SAB. In addition, with the increase of the normalized intensity at the
      first peak, the focal position (second peak) of the MAAB remains almost the same,
      whereas the position of the first peak shifts along the propagation direction
      gradually. These unique characteristics of MAAB have been demonstrated by
      experiment and indicate potential applications in various fields.

PMID- 29036157
TI  - Nonlinear spline wavefront reconstruction from Shack-Hartmann intensity
      measurements through small aberration approximations.
AB  - We propose an extension of the Spline based ABerration Reconstruction (SABRE)
      method to Shack-Hartmann (SH) intensity measurements, through small aberration
      approximations of the focal spot models. The original SABRE for SH slope
      measurements is restricted to the use of linear spline polynomials, due to the
      limited amount of data, and the resolution of its reconstruction is determined by
      the number of lenslets. In this work, a fast algorithm is presented that directly
      processes the pixel information of the focal spots, allowing the employment of
      nonlinear polynomials for high accuracy reconstruction. In order to guarantee the
      validity of the small aberration approximations, the method is applied in two
      correction steps, with a first compensation of large, low-order aberrations
      through the gradient-based linear SABRE followed by compensation of the remaining
      high-order aberrations with the intensity-based nonlinear SABRE.

PMID- 29036158
TI  - Parabasal formulas and their applications.
AB  - Parabasal theory is a technique in geometrical optics, which describes the
      behavior of light rays located near some defined base ray rather than the optical
      axis. In this work, we are concerned with parabasal rays, which lie in a
      sufficiently small neighborhood of a chief ray and develop some formulas for the
      parabasal quantities of the chief ray. The parabasal quantities of a chief ray
      are shown to be intimately related to the coefficients of the first-order
      differential equations of the chief ray. Using the relations, we derive parabasal
      formulas containing parabasal refractive indices and parabasal powers from the
      first-order differential equations. These parabasal formulas turn out to be
      decoupled differential equations of the first-order differential equations so
      that highly coupled differential equations for a chief ray can be solved
      systematically. In addition, we apply parabasal formulas to the paraxial region
      by taking the limits of the formulas. These limits give necessary conditions
      expressed in terms of Gaussian brackets for various initial design requirements
      of optical lens systems. Those necessary conditions do not seem to be derivable
      by using only paraxial theory without the parabasal approaches developed in this
      work.

PMID- 29036159
TI  - Data-driven linearizing approach in inverse scattering.
AB  - Direct or forward wave scattering admits three classical regimes in which the map
      from scatterer properties or scattering potential to the data is linear, namely,
      the Born, Rytov, and physical optics approximations. In this paper we derive a
      new decomposition of the forward scattering map which reveals a previously
      unknown approximate bilinear forward scattering relation. The latter is data
      driven, i.e., it involves exact scattering data, and has the useful property that
      the dependence on the data and the potential is bilinear. This fundamental result
      naturally leads to a new linear inverse scattering approach that generalizes and
      is more broadly applicable than the classical Born-approximation-based imaging.
      The developed scattering and inverse scattering theory are presented in both
      plane wave and multipole expansion representations, and the possibility of
      exploiting support information is also formally addressed in the multipole
      domain. The paper includes computer simulations illustrating the derived theory
      and algorithms.

PMID- 29036160
TI  - On the van Cittert-Zernike theorem for intensity correlations and its
      applications.
AB  - A reciprocal relationship between the autocovariance of the light intensity in
      the source plane and in the far-field detector plane is presented in a form
      analogous to the classical van Cittert-Zernike theorem, but involving intensity
      correlation functions. A "classical" version of the reciprocity relationship is
      considered first, based on the assumption of circular Gaussian statistics of the
      complex amplitudes in the source plane. The result is consistent with the theory
      of Hanbury Brown-Twiss interferometry, but it is shown to be also applicable to
      estimation of the source size or the spatial resolution of the detector from the
      noise power spectrum of flat-field images. An alternative version of the van
      Cittert-Zernike theorem for intensity correlations is then derived for a
      quantized electromagnetic beam in a coherent state, which leads to Poisson
      statistics for the intrinsic intensity of the beam.

PMID- 29036161
TI  - Tensor decomposition-based sparsity divergence index for hyperspectral anomaly
      detection.
AB  - Recently, some methods exploiting both the spatial and spectral features have
      drawn increasing attention in hyperspectral anomaly detection (AD) and they
      perform well. In addition, a tensor decomposition-based (TenB) algorithm treating
      the hyperspectral dataset as a three-order tensor (two modes for space and one
      mode for spectra) has been proposed to further improve the performance for AD. In
      this paper, a method using the sparsity divergence index (SDI) based on tensor
      decomposition (SDI-TD) is proposed. First, three modes of the hyperspectral
      dataset are obtained by tensor decomposition. Then, low-rank and sparse matrix
      decomposition is employed separately along the three modes and three sparse
      matrices are acquired. Finally, SDIs based on the three sparse matrices along the
      three modes are obtained, and the final result is generated by using the joint
      SDI. Experiments tested on the real and synthetic hyperspectral dataset reveal
      that the proposed SDI-TD performs better than the comparison algorithms.

PMID- 29036162
TI  - Analysis of laser speckle reduction utilizing microlens-array-based projection
      screen.
AB  - This paper focuses on the theoretical analyzation of laser speckle reduction by
      utilizing a microlens array (MLA). A theoretical model was established to
      describe the screen effect on speckle reduction, taking into account MLA cell
      size and on-screen projection/detection resolution area size. The relationship
      between the speckle contrast ratio (SCR) of a projection system and the cell size
      of an MLA was studied and investigated. A guideline for choosing an MLA that is
      able to suppress SCR below the threshold of human perception is proposed from the
      obtained results.

PMID- 29036163
TI  - Propagation of uncertainties and applications in numerical modeling: tutorial.
AB  - Some inputs of computational models are commonly retrieved from external sources
      (handbooks, articles, dedicated measurements), and therefore are subject to
      uncertainties. The known experimental dispersion of the inputs can be propagated
      through the numerical models to produce samples of outputs. The stemming
      propagation of uncertainties is already significant in metrology but also has
      applications in optimization and inverse problem resolution of the modeled
      physical system. Moreover, the information on uncertainties can be used to
      characterize and compare models, and to deduce behavior laws. This tutorial gives
      tools and applications of the propagation of experimental uncertainties through
      models. To illustrate the method and its applications, we propose to investigate
      the scattering of light by gold nanoparticles, which also enables the comparison
      of the full Mie theory and the dipole approximation. The position of the
      localized surface plasmon resonance and the corresponding value of the scattering
      efficiency are more specifically studied.

PMID- 29036164
TI  - Crossing statistics of laser light scattered through a nanofluid.
AB  - In this paper, we investigate the crossing statistics of speckle patterns formed
      in the Fresnel diffraction region by a laser beam scattering through a nanofluid.
      We extend zero-crossing statistics to assess the dynamical properties of the
      nanofluid. According to the joint probability density function of laser beam
      fluctuation and its time derivative, the theoretical frameworks for Gaussian and
      non-Gaussian regimes are revisited. We count the number of crossings not only at
      zero level but also for all available thresholds to determine the average speed
      of moving particles. Using a probabilistic framework in determining crossing
      statistics, a priori Gaussianity is not essentially considered; therefore, even
      in the presence of deviation from Gaussian fluctuation, this modified approach is
      capable of computing relevant quantities, such as mean value of speed, more
      precisely. Generalized total crossing, which represents the weighted summation of
      crossings for all thresholds to quantify small deviation from Gaussian
      statistics, is introduced. This criterion can also manipulate the contribution of
      noises and trends to infer reliable physical quantities. The characteristic time
      scale for having successive crossings at a given threshold is defined. In our
      experimental setup, we find that increasing sample temperature leads to more
      consistency between Gaussian and perturbative non-Gaussian predictions. The
      maximum number of crossings does not necessarily occur at mean level, indicating
      that we should take into account other levels in addition to zero level to
      achieve more accurate assessments.

PMID- 29036165
TI  - Modeling open nanophotonic systems using the Fourier modal method: generalization
      to 3D Cartesian coordinates.
AB  - Recently, an open geometry Fourier modal method based on a new combination of an
      open boundary condition and a non-uniform k-space discretization was introduced
      for rotationally symmetric structures, providing a more efficient approach for
      modeling nanowires and micropillar cavities [J. Opt. Soc. Am. A33, 1298
      (2016)JOAOD61084-752910.1364/JOSAA.33.001298]. Here, we generalize the approach
      to three-dimensional (3D) Cartesian coordinates, allowing for the modeling of
      rectangular geometries in open space. The open boundary condition is a
      consequence of having an infinite computational domain described using basis
      functions that expand the whole space. The strength of the method lies in
      discretizing the Fourier integrals using a non-uniform circular "dartboard"
      sampling of the Fourier k space. We show that our sampling technique leads to a
      more accurate description of the continuum of the radiation modes that leak out
      from the structure. We also compare our approach to conventional discretization
      with direct and inverse factorization rules commonly used in established Fourier
      modal methods. We apply our method to a variety of optical waveguide structures
      and demonstrate that the method leads to a significantly improved convergence,
      enabling more accurate and efficient modeling of open 3D nanophotonic structures.

PMID- 29036166
TI  - Asymptotic theory of circular polarization memory.
AB  - We establish a quantitative theory of circular polarization memory, which is the
      unexpected persistence of the incident circular polarization state in a strongly
      scattering medium. Using an asymptotic analysis of the three-dimensional vector
      radiative transfer equation (VRTE) in the limit of strong scattering, we find
      that circular polarization memory must occur in a boundary layer near the portion
      of the boundary on which polarized light is incident. The boundary layer solution
      satisfies a one-dimensional conservative scattering VRTE. Through a spectral
      analysis of this boundary layer problem, we introduce the dominant mode, which is
      the slowest-decaying mode in the boundary layer. To observe circular polarization
      memory for a particular set of optical parameters, we find that this dominant
      mode must pass three tests: (1) this dominant mode is given by the largest,
      discrete eigenvalue of a reduced problem that corresponds to Fourier mode k=0 in
      the azimuthal angle, and depends only on Stokes parameters U and V; (2) the
      polarization state of this dominant mode is largely circular polarized so that
      |V|?|U|; and (3) the circular polarization of this dominant mode is maintained
      for all directions so that V is sign-definite. By applying these three tests to
      numerical calculations for monodisperse distributions of Mie scatterers, we
      determine the values of the size and relative refractive index when circular
      polarization memory occurs. In addition, we identify a reduced, scalar-like
      problem that provides an accurate approximation for the dominant mode when
      circular polarization memory occurs.

PMID- 29036167
TI  - Development and validation of a protocol for optimizing the use of paraffin
      blocks in molecular epidemiological studies: The example from the HPV-AHEAD
      study.
AB  - Worldwide use of formalin-fixed paraffin-embedded blocks (FFPE) is extensive in
      diagnosis and research. Yet, there is a lack of optimized/standardized protocols
      to process the blocks and verify the quality and presence of the targeted tissue.
      In the context of an international study on head and neck cancer (HNC)-HPV-AHEAD,
      a standardized protocol for optimizing the use of FFPEs in molecular epidemiology
      was developed and validated. First, a protocol for sectioning the FFPE was
      developed to prevent cross-contamination and distributed between participating
      centers. Before processing blocks, all sectioning centers underwent a quality
      control to guarantee a satisfactory training process. The first and last sections
      of the FFPEs were used for histopathological assessment. A consensus
      histopathology evaluation form was developed by an international panel of
      pathologists and evaluated for four indicators in a pilot analysis in order to
      validate it: 1) presence/type of tumor tissue, 2) identification of other tissue
      components that could affect the molecular diagnosis and 3) quality of the
      tissue. No HPV DNA was found in sections from empty FFPE generated in any
      histology laboratories of HPV-AHEAD consortium and all centers passed quality
      assurance for processing after quality control. The pilot analysis to validate
      the histopathology form included 355 HNC cases. The form was filled by six
      pathologists and each case was randomly assigned to two of them. Most samples
      (86%) were considered satisfactory. Presence of >50% of invasive carcinoma was
      observed in all sections of 66% of cases. Substantial necrosis (>50%) was present
      in <2% of samples. The concordance for the indicators targeted to validate the
      histopathology form was very high (kappa > 0.85) between first and last sections
      and fair to high between pathologists (kappa/pabak 0.21-0.72). The protocol
      allowed to correctly process without signs of contamination all FFPE of the
      study. The histopathology evaluation of the cases assured the presence of the
      targeted tissue, identified the presence of other tissues that could disturb the
      molecular diagnosis and allowed the assessment of tissue quality.

PMID- 29036168
TI  - A machine learning approach for predicting CRISPR-Cas9 cleavage efficiencies and
      patterns underlying its mechanism of action.
AB  - The adaptation of the CRISPR-Cas9 system as a genome editing technique has
      generated much excitement in recent years owing to its ability to manipulate
      targeted genes and genomic regions that are complementary to a programmed single
      guide RNA (sgRNA). However, the efficacy of a specific sgRNA is not uniquely
      defined by exact sequence homology to the target site, thus unintended off
      targets might additionally be cleaved. Current methods for sgRNA design are
      mainly concerned with predicting off-targets for a given sgRNA using basic
      sequence features and employ elementary rules for ranking possible sgRNAs. Here,
      we introduce CRISTA (CRISPR Target Assessment), a novel algorithm within the
      machine learning framework that determines the propensity of a genomic site to be
      cleaved by a given sgRNA. We show that the predictions made with CRISTA are more
      accurate than other available methodologies. We further demonstrate that the
      occurrence of bulges is not a rare phenomenon and should be accounted for in the
      prediction process. Beyond predicting cleavage efficiencies, the learning process
      provides inferences regarding patterns that underlie the mechanism of action of
      the CRISPR-Cas9 system. We discover that attributes that describe the spatial
      structure and rigidity of the entire genomic site as well as those surrounding
      the PAM region are a major component of the prediction capabilities.

PMID- 29036169
TI  - Developing a dengue forecast model using machine learning: A case study in China.
AB  - BACKGROUND: In China, dengue remains an important public health issue with
      expanded areas and increased incidence recently. Accurate and timely forecasts of
      dengue incidence in China are still lacking. We aimed to use the state-of-the-art
      machine learning algorithms to develop an accurate predictive model of dengue.
      METHODOLOGY/PRINCIPAL FINDINGS: Weekly dengue cases, Baidu search queries and
      climate factors (mean temperature, relative humidity and rainfall) during 2011
      2014 in Guangdong were gathered. A dengue search index was constructed for
      developing the predictive models in combination with climate factors. The
      observed year and week were also included in the models to control for the long
      term trend and seasonality. Several machine learning algorithms, including the
      support vector regression (SVR) algorithm, step-down linear regression model,
      gradient boosted regression tree algorithm (GBM), negative binomial regression
      model (NBM), least absolute shrinkage and selection operator (LASSO) linear
      regression model and generalized additive model (GAM), were used as candidate
      models to predict dengue incidence. Performance and goodness of fit of the models
      were assessed using the root-mean-square error (RMSE) and R-squared measures. The
      residuals of the models were examined using the autocorrelation and partial
      autocorrelation function analyses to check the validity of the models. The models
      were further validated using dengue surveillance data from five other provinces.
      The epidemics during the last 12 weeks and the peak of the 2014 large outbreak
      were accurately forecasted by the SVR model selected by a cross-validation
      technique. Moreover, the SVR model had the consistently smallest prediction error
      rates for tracking the dynamics of dengue and forecasting the outbreaks in other
      areas in China. CONCLUSION AND SIGNIFICANCE: The proposed SVR model achieved a
      superior performance in comparison with other forecasting techniques assessed in
      this study. The findings can help the government and community respond early to
      dengue epidemics.

PMID- 29036170
TI  - Quantifying the effects of temperature on mosquito and parasite traits that
      determine the transmission potential of human malaria.
AB  - Malaria transmission is known to be strongly impacted by temperature. The current
      understanding of how temperature affects mosquito and parasite life history
      traits derives from a limited number of empirical studies. These studies, some
      dating back to the early part of last century, are often poorly controlled, have
      limited replication, explore a narrow range of temperatures, and use a mixture of
      parasite and mosquito species. Here, we use a single pairing of the Asian
      mosquito vector, An. stephensi and the human malaria parasite, P. falciparum to
      conduct a comprehensive evaluation of the thermal performance curves of a range
      of mosquito and parasite traits relevant to transmission. We show that biting
      rate, adult mortality rate, parasite development rate, and vector competence are
      temperature sensitive. Importantly, we find qualitative and quantitative
      differences to the assumed temperature-dependent relationships. To explore the
      overall implications of temperature for transmission, we first use a standard
      model of relative vectorial capacity. This approach suggests a temperature
      optimum for transmission of 29 degrees C, with minimum and maximum temperatures
      of 12 degrees C and 38 degrees C, respectively. However, the robustness of the
      vectorial capacity approach is challenged by the fact that the empirical data
      violate several of the model's simplifying assumptions. Accordingly, we present
      an alternative model of relative force of infection that better captures the
      observed biology of the vector-parasite interaction. This model suggests a
      temperature optimum for transmission of 26 degrees C, with a minimum and maximum
      of 17 degrees C and 35 degrees C, respectively. The differences between the
      models lead to potentially divergent predictions for the potential impacts of
      current and future climate change on malaria transmission. The study provides a
      framework for more detailed, system-specific studies that are essential to
      develop an improved understanding on the effects of temperature on malaria
      transmission.

PMID- 29036171
TI  - Costs of facility-based HIV testing in Malawi, Zambia and Zimbabwe.
AB  - BACKGROUND: Providing HIV testing at health facilities remains the most common
      approach to ensuring access to HIV treatment and prevention services for the
      millions of undiagnosed HIV-infected individuals in sub-Saharan Africa. We sought
      to explore the costs of providing these services across three southern African
      countries with high HIV burden. METHODS: Primary costing studies were undertaken
      in 54 health facilities providing HIV testing services (HTS) in Malawi, Zambia
      and Zimbabwe. Routinely collected monitoring and evaluation data for the health
      facilities were extracted to estimate the costs per individual tested and costs
      per HIV-positive individual identified. Costs are presented in 2016 US dollars.
      Sensitivity analysis explored key drivers of costs. RESULTS: Health facilities
      were testing on average 2290 individuals annually, albeit with wide variations.
      The mean cost per individual tested was US$5.03.9 in Malawi, US$4.24 in Zambia
      and US$8.79 in Zimbabwe. The mean cost per HIV-positive individual identified was
      US$79.58, US$73.63 and US$178.92 in Malawi, Zambia and Zimbabwe respectively.
      Both cost estimates were sensitive to scale of testing, facility staffing levels
      and the costs of HIV test kits. CONCLUSIONS: Health facility based HIV testing
      remains an essential service to meet HIV universal access goals. The low costs
      and potential for economies of scale suggests an opportunity for further scale
      up. However low uptake in many settings suggests that demand creation or
      alternative testing models may be needed to achieve economies of scale and reach
      populations less willing to attend facility based services.

PMID- 29036172
TI  - A question of data quality-Testing pollination syndromes in Balsaminaceae.
AB  - Pollination syndromes and their predictive power regarding actual plant-animal
      interactions have been controversially discussed in the past. We investigate
      pollination syndromes in Balsaminaceae, utilizing quantitative respectively
      categorical data sets of flower morphometry, signal and reward traits for 86
      species to test for the effect of different types of data on the test patterns
      retrieved. Cluster Analyses of the floral traits are used in combination with
      independent pollinator observations. Based on quantitative data we retrieve seven
      clusters, six of them corresponding to plausible pollination syndromes and one
      additional, well-supported cluster comprising highly divergent floral
      architectures. This latter cluster represents a non-syndrome of flowers not
      segregated by the specific data set here used. Conversely, using categorical data
      we obtained only a rudimentary resolution of pollination syndromes, in line with
      several earlier studies. The results underscore that the use of functional,
      exactly quanitified trait data has the power to retrieve pollination syndromes
      circumscribed by the specific data used. Data quality can, however, not be
      replaced by sheer data volume. With this caveat, it is possible to identify
      pollination syndromes from large datasets and to reliably extrapolate them for
      taxa for which direct observations are unavailable.

PMID- 29036173
TI  - Pre-treatment with GnRHa or ulipristal acetate prior to laparoscopic and
      laparotomic myomectomy: A systematic review and meta-analysis.
AB  - BACKGROUND: Myomectomy has potential risks of complications. To reduce these
      risks, medical pre-treatment can be applied to reduce fibroid size and thereby
      potentially decrease intra-operative blood loss, the need for blood transfusion
      and emergency hysterectomy. The aim of this systematic review and meta-analysis
      is to study the effectiveness of medical pre-treatment with Gonadotropin
      releasing hormone agonists (GnRHa) or ulipristal acetate prior to laparoscopic or
      laparotomic myomectomy on intra-operative and post-operative outcomes. METHODS:
      We performed an extensive search in Embase.com, Wiley/Cochrane Library and PubMed
      in accordance with the Prisma guidelines. All studies published as full papers in
      peer reviewed journals using GnRHa or ulipristal acetate as medical pre-treatment
      independent of route of administration or dosage before laparotomic or
      laparoscopic myomectomy were included. The primary outcome was duration of
      surgery. Secondary outcomes were duration of enucleation, blood loss, degree of
      difficulty of surgery, identification of cleavage planes, proportion of vertical
      incisions, conversion rate, frequency of blood transfusions, post-operative
      complications, duration of hospital stay, frequency of recurrence of fibroids,
      frequency of uterine adhesions, recovery time and quality of life. No language
      restrictions were applied. Meta-analysis were performed where possible. FINDINGS:
      Twenty-three studies were included. In laparotomic myomectomy, pre-treatment with
      GnRHa decreases intra-operative blood loss with 97.39ml (95% CI -111.80 to 
      82.97) compared to no pre-treatment or placebo. Pre-treatment with GnRHa before
      laparoscopic myomectomies also shows a reduction in intra-operative blood loss by
      23.03ml (95% CI -40.79 to -5.27) and in the frequency of blood transfusions (OR
      0.17, 95% CI 0.05 to 0.55) compared to no pre-treatment. Only two retrospective
      cohort studies reported on pre-treatment with ulipristal acetate compared to no
      pre-treatment before laparoscopic myomectomy showing a statistically significant
      reduction in intra-operative blood loss, duration of surgery and frequency of
      blood transfusions after pre-treatment with ulipristal acetate. CONCLUSION:
      Administration of GnRHa prior to laparotomic myomectomy reduces blood loss and
      might decrease uterine adhesion formation. Pre-treatment with GnRHa before
      laparoscopic myomectomy reduces blood loss, the frequency of blood transfusions
      and might increase recurrence rate of fibroids, however it should be taken into
      account that some results are mainly based on cohort studies. Other pre-treatment
      agent ulipristal acetate has not been investigated sufficiently for relevant
      surgical outcomes.

PMID- 29036174
TI  - Equity in international health research collaborations in Africa: Perceptions and
      expectations of African researchers.
AB  - INTRODUCTION AND METHOD: Africa is currently host to a number of international
      genomics research and biobanking consortia, each with a mandate to advance
      genomics research and biobanking in Africa. Whilst most of these consortia
      promise to transform the way international health research is done in Africa, few
      have articulated exactly how they propose to go about this. In this paper, we
      report on a qualitative interviewing study in which we involved 17 genomics
      researchers in Africa. We describe their perceptions and expectations of
      international genomics research and biobanking initiatives in Africa. RESULTS:
      All interviewees were of the view that externally funded genomics research and
      biobanking initiatives in Africa, have played a critical role in building
      capacity for genomics research and biobanking in Africa and in providing an
      opportunity for researchers in Africa to collaborate and network with other
      researchers. Whilst the opportunity to collaborate was seen as a benefit, some
      interviewees stressed the importance of recognizing that these collaborations
      carry mutual benefits for all partners, including their collaborators in HICs.
      They also voiced two major concerns of being part of these collaborative
      initiatives: the possibility of exploitation of African researchers and the non
      sustainability of research capacity building efforts. As a way of minimising
      exploitation, researchers in Africa recommended that genuine efforts be made to
      create transparent and equitable international health research partnerships. They
      suggested that this could be achieved through,: having rules of engagement,
      enabling African researchers to contribute to the design and conduct of
      international health projects in Africa, and mutual and respectful exchange of
      experience and capacity between research collaborators. These were identified as
      hallmarks to equitable international health research collaborations in Africa.
      CONCLUSION: Genomics research and biobanking initiatives in Africa such as
      H3Africa have gone some way in defining aspects of fair and equitable research
      collaborations in Africa. However, they will need to strive at achieving
      equitable health research collaborations if they truly aim at setting a gold
      standard for how international health research should be conducted in Africa.

PMID- 29036175
TI  - The efficiency of aspheric intraocular lens according to biometric measurements.
AB  - PURPOSE: To analyze internal spherical aberration in pseudophakic eyes that
      underwent aspheric intraocular lens (IOL) implantation, and to investigate the
      relationships between biometric data and the effectiveness of aspheric IOL
      implantation. METHODS: This retrospective study included 40 eyes of 40 patients
      who underwent implantation of an IOL having a negative spherical aberration of 
      0.20 MUm (CT ASPHINA 509M; Carl Zeiss Meditec Inc., Germany). The IOLMaster
      (version 5.0; Carl Zeiss AG, Germany) was used for preoperative biometric
      measurements (axial length, anterior chamber depth, central corneal power) and
      the measurement of postoperative anterior chamber depth. The spherical
      aberrations were measured preoperatively and 3 months postoperatively using the
      iTrace (Tracey Technologies, Houston, TX, USA) at a pupil diameter of 5.0 mm. We
      investigated the relationships between preoperative biometric data and
      postoperative internal spherical aberration, and compared biometric measurements
      between 2 subgroups stratified according to internal spherical aberration
      (spherical aberration <= -0.06 MUm vs. spherical aberration > -0.06 MUm).
      RESULTS: The mean postoperative internal spherical aberration was -0.087 +/-
      0.063 MUm. Preoperative axial length and residual total spherical aberration
      showed statistically significant correlations with internal spherical aberration
      (p = 0.041, 0.002). Preoperative axial length, postoperative anterior chamber
      depth, IOL power, and residual spherical aberration showed significant
      differences between the 2 subgroups stratified according to internal spherical
      aberration (p = 0.020, 0.029, 0.048, 0.041 respectively). CONCLUSION: The
      corrective effect of an aspheric IOL is influenced by preoperative axial length
      and postoperative anterior chamber depth. Not only the amount of negative
      spherical aberration on the IOL surface but also the preoperative axial length
      should be considered to optimize spherical aberration after aspheric IOL
      implantation.

PMID- 29036176
TI  - Association and clinical utility of NAT2 in the prediction of isoniazid-induced
      liver injury in Singaporean patients.
AB  - BACKGROUND AND AIMS: Isoniazid (INH) is part of the first-line-therapy for
      tuberculosis (TB) but can cause drug-induced liver injury (DILI). Several
      candidate single nucleotide polymorphisms (SNPs) have been previously identified
      but the clinical utility of these SNPs in the prediction of INH-DILI remains
      uncertain. The aim of this study was to assess the association between selected
      candidate SNPs and the risk of INH-DILI and to assess the clinical validity of
      associated variants in a Singaporean population. METHODS: This was a case-control
      study where 24 INH-DILI cases and 79 controls were recruited from the TB control
      unit in a tertiary hospital. Logistic regression was used to test for the
      association between candidate SNPs and INH-DILI. NAT2 acetylator status was
      inferred from genotypes and tested for association with INH-DILI. Finally,
      clinical validity measures were estimated for significant variants. RESULTS: Two
      SNPs in NAT2 (rs1041983 and rs1495741) and NAT2 slow acetylators (SA) were
      significantly associated with INH-DILI (OR (95% CI) = 13.86 (4.30-44.70), 0.10
      (0.03-0.33) and 9.98 (3.32-33.80), respectively). Based on an INH-DILI prevalence
      of 10%, the sensitivity, specificity, positive and negative predictive values of
      NAT2 SA were 75%, 78%, 28% and 97%, respectively. The population attributable
      fraction (PAF) and number needed to test (NNT) for NAT2 SA were estimated to be
      0.67 and 4.08, respectively. A model with clinical and NAT2 acetylator status
      provided significantly better prediction for INH-DILI than a clinical model alone
      (area under receiver operating characteristic curve = 0.863 vs. 0.766,
      respectively, p = 0.027). CONCLUSIONS: We show the association between NAT2 SA
      and INH-DILI in a Singaporean population and demonstrated its clinical utility in
      the prediction of INH-DILI.

PMID- 29036177
TI  - Dietary patterns in internal migrants in a continental country: A population
      based study.
AB  - OBJECTIVE: The objective of this study was to assess the differences and
      similarities in dietary patterns among migrants and natives. METHODS: A
      population-based, cross-sectional study was conducted in the city of Sao Paulo.
      The study population included internal migrants, defined as individuals born
      outside Sao Paulo city who had lived in the city for ten years or longer. The
      final population (n = 999) was divided into three groups: natives of Sao Paulo (n
      = 354), migrants from the Southeast (n = 349) and migrants from the Northeast (n
      = 296). Factor and principal component analysis was employed to derive dietary
      patterns. The standardized scores were compared among groups using linear
      regression. RESULTS: Differences in income per capita, years of education, self
      reported race, smoking habits, alcohol consumption, nutritional status and
      prevalence of hypertension were found for place of birth. Three dietary patterns
      were identified: prudent (salad dressings, vegetables, natural flavorings,
      fruits, whole-grain bread, white cheeses and juices), traditional (rice, beans,
      bread/toast/crackers, butter/margarine, whole milk, coffee/teas, sugar), and
      modern (sodas, pastries/sandwiches/pizzas, yellow cheeses, pastas, sauces,
      alcoholic beverages, sweets, processed meats). Compared to natives, migrants from
      the Southeast had an inversely proportional adherence to the modern pattern
      whereas migrants from the Northeast had an inverse association with the prudent
      and modern patterns and a positive association with the traditional pattern.
      CONCLUSIONS: Sao Paulo natives and internal migrants from other regions of Brazil
      exhibited different dietary patterns. The results presented here add perspectives
      to be considered in the study of non-communicable diseases and its different
      incidences among migrants and natives.

PMID- 29036178
TI  - Substantial population structure of Plasmodium vivax in Thailand facilitates
      identification of the sources of residual transmission.
AB  - BACKGROUND: Plasmodium vivax transmission in Thailand has been substantially
      reduced over the past 10 years, yet it remains highly endemic along international
      borders. Understanding the genetic relationship of residual parasite populations
      can help track the origins of the parasites that are reintroduced into malaria
      free regions within the country. METHODOLOGY/RESULTS: A total of 127 P. vivax
      isolates were genotyped from two western provinces (Tak and Kanchanaburi) and one
      eastern province (Ubon Ratchathani) of Thailand using 10 microsatellite markers.
      Genetic diversity was high, but recent clonal expansion was detected in all three
      provinces. Substantial population structure and genetic differentiation of
      parasites among provinces suggest limited gene flow among these sites. There was
      no haplotype sharing among the three sites, and a reduced panel of four
      microsatellite markers was sufficient to assign the parasites to their provincial
      origins. CONCLUSION/SIGNIFICANCE: Significant parasite genetic differentiation
      between provinces shows successful interruption of parasite spread within
      Thailand, but high diversity along international borders implies a substantial
      parasite population size in these regions. The provincial origin of P. vivax
      cases can be reliably determined by genotyping four microsatellite markers, which
      should be useful for monitoring parasite reintroduction after malaria
      elimination.

PMID- 29036179
TI  - Extreme strontium concentrations reveal specific biomineralization pathways in
      certain coccolithophores with implications for the Sr/Ca paleoproductivity proxy.
AB  - The formation of the coccolith biominerals by a group of marine algae (the
      Coccolithophores) offers fascinating research avenues both from the biological
      and geological sides. It is surprising how biomineralisation by a key
      phytoplanktonic group remains underconstrained, yet is influential on ocean
      alkalinity and responsible for the built up of our paleoclimatic archive over the
      last 200 Myrs. Here, we report two close relative coccolith taxa exhibiting
      substantial bioaccumulation of strontium: Scyphosphaera and Pontosphaera grown in
      the laboratory or retrieved from Pliocene sediments. This strontium enrichment
      relative to calcium is one order of magnitude greater than reported in other
      coccoliths of the orders Isochrysidales and Coccolithales, and extends well
      beyond established controls on Sr/Ca ratios by temperature and growth rate. We
      discuss this prominent vital effect in relation with possible specific uptake of
      strontium relative to calcium from the extracellular environment to the coccolith
      vesicle in coccolithophores excreting very large scale coccoliths. The report of
      Sr-rich biominerals challenges our current understanding of the cellular
      acquisition and intracellular trafficking of alkaline earth cations in
      phytoplanktonic calcifying eukaryotic algae. The presence of Sr-rich coccolith
      species in the geological record has to be quantitatively considered in future
      Sr/Ca-based palaeoceanographic reconstruction.

PMID- 29036180
TI  - Real and visually-induced body inclination differently affect the perception of
      object stability.
AB  - The prediction of object stability on earth requires the establishment of a
      perceptual frame of reference based on the direction of gravity. Across three
      experiments, we measured the critical angle (CA) at which an object appeared
      equally likely to fall over or right itself. We investigated whether the internal
      representation of the gravity direction, biased by either simulated tilt
      (rotating visual surround) or real body tilt situations, influences in a similar
      fashion the judgment of stability. In the simulated tilt condition, the estimated
      CA and the perceived gravity are both deviated in the same direction. In the real
      tilt condition, the orientation of the body affects the perception of gravity
      direction but has no effect on the estimated CA. Results suggest that people
      differently weigh gravity direction information provided by visual motion and by
      visual polarity cues for estimating the stability of objects.

PMID- 29036181
TI  - Juvenile myasthenia gravis in Norway: HLA-DRB1*04:04 is positively associated
      with prepubertal onset.
AB  - BACKGROUND: Juvenile myasthenia gravis (MG) is a rare autoantibody mediated
      autoimmune disorder targeting the neuromuscular endplate. The clinical hallmark
      is muscle weakness and fatigability. Disease aetiology is complex, including both
      genetic and environmental factors. The involvement of genes in the human
      leukocyte antigen (HLA) is well established in adult MG. However, HLA
      associations in European juvenile MG have not been studied. This case-control
      study aimed to investigate and characterize genetic risk factors in prepubertal
      and postpubertal onset juvenile MG. METHODOLOGY/PRINCIPAL FINDINGS: A population
      based Norwegian cohort of 43 juvenile MG patients (17 with prepubertal onset, 26
      with postpubertal onset) and 368 controls were included. Next generation
      sequencing of five HLA loci (HLA-A, -B, -C, -DRB1 and -DQB1) was performed, and a
      positive association was seen with HLA-B*08 (OR (95% CI) = 3.27 (2.00-5.36), Pc =
      0.00003) and HLA-DRB1*04:04 (OR (95% CI) = 2.65 (1.57-4.24), Pc = 0.03).
      Stratified in postpubertal and prepubertal onset, HLA-DRB1*04:04 was only
      positively associated with the latter (P = 0.01). The HLA-B*08 allele (12.9% in
      the controls), previously described associated with early onset adult MG, was
      most frequently observed in postpubertal onset MG (40.4%, P = 0.0002) but also
      increased among prepubertal onset MG (23.5%, P = 0.05). CONCLUSION: This study
      provides novel information about HLA susceptibility alleles in Norwegian juvenile
      MG where HLA-DRB1*04:04 was associated with prepubertal onset.

PMID- 29036182
TI  - Proteome analysis of bronchoalveolar lavage from calves infected with bovine
      respiratory syncytial virus-Insights in pathogenesis and perspectives for new
      treatments.
AB  - Human and bovine respiratory syncytial viruses (HRSV/BRSV) are major causes of
      severe lower respiratory tract infections in children and calves, respectively.
      Shared epidemiological, clinical, pathological and genetic characteristics of
      these viruses make comparative research highly relevant. To characterise the host
      response against BRSV infection, bronchoalveolar lavage supernatant (BAL) from i)
      non-vaccinated, BRSV-infected ii) vaccinated, BRSV-infected and iii) non-infected
      calves was analysed by tandem mass spectrometry. Proteins were semi-quantified
      and protein expression was validated by immunoblotting. Correlations between
      selected proteins and pathology, clinical signs and virus shedding were
      investigated. Calves with BRSV-induced disease had increased total protein
      concentrations and a decreased number of proteins identified in BAL. The protein
      profile was characterised by neutrophil activation and a reduction in identified
      antioxidant enzymes. The presence of neutrophils in alveolar septa, the
      expression level of neutrophil-related or antioxidant proteins and LZTFL1
      correlated significantly with disease. Citrullinated histone 3, an indicator of
      extracellular traps (ETs), was only detected in non-vaccinated, BRSV-infected
      animals. By bringing disequilibrium in the release and detoxification of reactive
      oxygen species, generating ETs and causing elastine degradation, exaggerated
      neutrophil responses might exacerbate RSV-induced disease. Neutrophil-mitigating
      or antioxidant treatments should be further explored.

PMID- 29036183
TI  - MRI-assessed atrophy subtypes in Alzheimer's disease and the cognitive reserve
      hypothesis.
AB  - BACKGROUND/AIMS: MRI assessment of the brain has demonstrated four different
      patterns of atrophy in patients with Alzheimer's disease dementia (AD): typical
      AD, limbic-predominant AD, hippocampal-sparing AD, and a subtype with minimal
      atrophy, previously referred to as no-atrophy AD. The aim of the present study
      was to identify and describe the differences between these four AD subtypes in a
      longitudinal memory-clinic study. METHODS: The medial temporal lobes, the frontal
      regions, and the posterior regions were assessed with MRI visual rating scales to
      categorize 123 patients with mild AD according to ICD-10 and NINCDS-ADRDA
      criteria and the clinical dementia rating scale (CDR) into atrophy subtypes.
      Demographic data, neuropsychological measures, cerebrospinal-fluid biomarkers,
      and progression rate of dementia at two-year follow-up were compared between the
      groups. RESULTS: Typical AD was found in 59 patients (48%); 29 (24%) patients had
      limbic-predominant AD; 19 (15%) had hippocampal-sparing AD; and 16 (13%) belonged
      to the group with minimal atrophy. No differences were found regarding cognitive
      test results or progression rates between the different subtypes. Using adjusted
      logistic regression analysis, we found that the patients in the minimal-atrophy
      group were less educated, had a lower baseline CDR sum of boxes score, and had
      higher levels of amyloid beta in the cerebrospinal fluid. CONCLUSION: Previous
      results concerning the prevalence and the similar phenotypic expressions of the
      four AD subtypes were confirmed. The main finding was that patients with minimal
      atrophy as assessed by MRI had less education than the other AD subtypes and that
      this could support the cognitive reserve hypothesis and, at least in part,
      explain the lower degree of atrophy in this group. Patients with less formal
      education might present with clinically typical AD symptoms before they have
      positive biomarkers of AD and this finding might challenge suggested biomarker
      based criteria for AD.

PMID- 29036184
TI  - Proinflammatory response of canine trophoblasts to Brucella canis infection.
AB  - Brucella canis infection is an important cause of late-term abortion in pregnant
      bitches. The pathophysiological mechanisms leading to B. canis-induced abortion
      are unknown, but heavily infected trophoblasts are consistently observed. As
      trophoblasts responses to other pathogens contribute to placental inflammation
      leading to abortion, the aim of the present study was to characterize the
      cytokine response of canine trophoblasts to B. canis infection. To achieve this,
      trophoblasts isolated from term placenta of healthy female dogs were infected
      with B. canis, culture supernatants were harvested for cytokine determinations,
      and the load of intracellular viable B. canis was determined at different times
      post-infection. Additionally, cytokine responses were assessed in non-infected
      trophoblasts stimulated with conditioned media (CM) from B. canis-infected canine
      monocytes and neutrophils. Finally, cytokine response and bacteria replication
      were assessed in canine placental explants infected ex vivo. B. canis
      successfully infected and replicated in primary canine trophoblasts, eliciting an
      increase in IL-8 and RANTES (CCL5) secretion. Moreover, the stimulation of
      trophoblasts with CM from B. canis-infected monocytes and neutrophils induced a
      significant increase in IL-8, IL-6 and RANTES secretion. B. canis replication was
      confirmed in infected placental explants and the infection elicited an increased
      secretion of TNF-alpha, IL-8, IL-6 and RANTES. This study shows that canine
      trophoblasts produce proinflammatory cytokines in response to B. canis infection
      and/or to stimulation with factors produced by infected monocytes and
      neutrophils. These cytokines may contribute to placental inflammation leading to
      abortion in B. canis-infected pregnant bitches.

PMID- 29036185
TI  - Impact of social inequalities at birth on the longevity of children born 1914
      1916: A cohort study.
AB  - BACKGROUND: Testing whether familial socioeconomic status (SES) in childhood is a
      predictor of mortality has rarely been done on historical cohorts. METHODS: The
      birth certificates of 4,805 individuals born 1914-1916 in 16 districts of the
      Paris region were retrieved. The handwritten information provided the occupation
      of parents, the legitimacy status, life events (e.g. marriage, divorce), and the
      precise date of death when after 1945 (i.e. age 31 years (y) in the cohort). We
      used the median age at death (MAD) as a global measure of mortality, then studied
      separately survival to and after 31 y. Multivariate Imputation by Chained
      Equations (MICE), Generalized Additive Models (GAMs) and mixed effect Cox models
      were used. RESULTS: MAD showed large variations according to paternal occupation.
      The lowest MAD in both sexes was that of workers' children: it was 56.3 y (95%
      CI: [48.6-62.7]) in men and 67.4 y (95% CI: [60.8-72.7]) in women, respectively
      (95% CI: 13.4 y [5.7-21.3]) and 12.3 y (95% CI: [4.0-19.2]) below the highest MAD
      attained. MAD experienced by illegitimate children was 18.9 y (95% CI: [13.3
      32.3]) shorter than of legitimate children. The multivariate analysis revealed
      that in both sexes survival to age 31 y was predicted independently by legitimacy
      and paternal occupation. Paternal occupation was found significantly associated
      with mortality after age 31 y in females only: accordingly difference in life
      expectancy at age 31 y was 4.4 y (95% CI: [1.2-7.6]) between upper class and
      workers' daughters. CONCLUSIONS: Paternal occupation and legitimacy status were
      strong predictors of offspring longevity in this one-century historical cohort
      born during World War One.

PMID- 29036186
TI  - The MGMT promoter single-nucleotide polymorphism rs1625649 had prognostic impact
      on patients with MGMT methylated glioblastoma.
AB  - Promoter methylation is the most significant mechanism to regulate O6
      methylguanine-DNA-methyltransferase (MGMT) expression. Single-nucleotide
      polymorphisms (SNPs) in the MGMT promoter region may also play a role. The aim of
      this study was to evaluate the clinical significance of SNPs in the MGMT promoter
      region of glioblastoma. Genomic DNAs from 118 glioblastomas were collected for
      polymerase chain reaction (PCR) amplification. Sanger sequencing was used to
      sequence the MGMT promoter region to detect SNPs. The results were correlated
      with MGMT status and patient survival. Rs1625649 was the only polymorphic SNP
      located at the MGMT promoter region in 37.5% of glioblastomas. Homozygous
      rs1625649 (AA genotype) was correlated with a higher MGMT methylation level and a
      lower protein expression, but the result was not statistically significant. In
      patients with MGMT methylated glioblastoma, cases with homozygous rs1625649 (AA
      genotype) were significantly associated with a lack of MGMT protein expression
      and a better progression-free survival (PFS) than the cases with wild type
      rs1625649 (CC genotype) or heterozygous rs1625649 (CA genotype). The survival
      impact was significant in multivariate analyses. In conclusion, the MGMT promoter
      homozygous rs1625649 (AA genotype) was found to correlate with a better PFS in
      patients with MGMT methylated glioblastoma.

PMID- 29036187
TI  - Analysis of transient hypermorphic activity of E(spl)D during R8 specification.
AB  - Drosophila atonal (ato) is required for the specification of founding R8
      photoreceptors during retinal development. ato is regulated via dual eye-specific
      enhancers; ato-3' is subject to initial induction whereas 5'-ato facilitates
      Notch-mediated autoregulation. Notch is further utilized to induce bHLH
      repressors of the E(spl) locus to restrict Ato from its initial broad expression
      to individual cells. Although Notch operates in two, distinct phases, it has
      remained unclear how the two phases maintain independence from one another. The
      difference in these two phases has attributed to the hypothesized delayed
      expression of E(spl). However, immunofluorescence data indicate that E(spl) are
      expressed during early Ato patterning, suggesting a more sophisticated underlying
      mechanism. To probe this mechanism, we provide evidence that although E(spl)
      exert no influence on ato-3', E(spl) repress 5'-ato and deletion of the E(spl)
      locus elicits precocious 5'-ato activity. Thus, E(spl) imposes a delay to the
      timing in which Ato initiates autoregulation. We next sought to understand this
      finding in the context of E(spl)D, which encodes a dysregulated variant of
      E(spl)M8 that perturbs R8 patterning, though, as previously reported, only in
      conjunction with the mutant receptor Nspl. We established a genetic interaction
      between E(spl)D and roughened eye (roe), a known modulator of Notch signaling in
      retinogenesis. This link further suggests a dosage-dependence between E(spl) and
      the proneural activators Ato and Sens, as indicated via interaction assays in
      which E(spl)D renders aberrant R8 patterning in conjunction with reduced
      proneural dosage. In total, the biphasicity of Notch signaling relies, to some
      degree, on the post-translational regulation of individual E(spl) members and,
      importantly, that post-translational regulation is likely necessary to modulate
      the level of E(spl) activity throughout the progression of Ato expression.

PMID- 29036188
TI  - Family functioning, parenting stress and quality of life in mothers and fathers
      of Polish children with high functioning autism or Asperger syndrome.
AB  - The aim of the study was to investigate the perception of the family functioning
      in parents of children with autism spectrum disorders (ASD) with normal-range
      intelligence and the relationships between family functioning, parenting stress
      and quality of life. Dyads of parents of children with ASD without intellectual
      disability and parents of typically developing children (controls) completed a
      set of self-report questionnaires. Parents of children with ASD reported lower
      functioning of the family as a whole and their own functioning as family members;
      they exhibited higher levels of parenting stress and lower quality of life.
      Mothers of children with ASD experienced more stress in personal domain than
      fathers. Relationships between family functioning, parenting stress and quality
      of life have been established. There were also moderate to strong correlations in
      mother-father dyads between their assessments of family functioning, parenting
      stress and QoL in social relationships and environmental domains.

PMID- 29036189
TI  - Inhibition of CUG-binding protein 1 and activation of caspases are critically
      involved in piperazine derivative BK10007S induced apoptosis in hepatocellular
      carcinoma cells.
AB  - Though piperazine derivative BK10007S was known to induce apoptosis in pancreatic
      cancer xenograft model as a T-type CaV3.1 a1G isoform calcium channel blocker,
      its underlying antitumor mechanism still remains unclear so far. Thus, in the
      present study, the antitumor mechanism of BK10007S was elucidated in
      hepatocellular carcinoma cells (HCCs). Herein, BK10007S showed significant
      cytotoxicity by 3-[4,5-2-yl]-2,5-diphenyltetra-zolium bromide (MTT) assay and
      anti-proliferative effects by colony formation assay in HepG2 and SK-Hep1 cells.
      Also, apoptotic bodies and terminal deoxynucleotidyl transferase (TdT) dUTP Nick
      End Labeling (TUNEL) positive cells were observed in BK10007S treated HepG2 and
      SK-Hep1 cells by 4',6-diamidino-2-phenylinodole (DAPI) staining and TUNEL assay,
      respectively. Consistently, BK10007S increased sub G1 population in HepG2 and SK
      Hep1 cells by cell cycle analysis. Furthermore, Western blotting revealed that
      BK10007S activated the caspase cascades (caspase 8, 9 and 3), cleaved poly (ADP
      ribose) polymerase (PARP), and downregulated the expression of cyclin D1,
      survivin and for CUG-binding protein 1 (CUGBP1 or CELF1) in HepG2 and SK-Hep1
      cells. Conversely, overexpression of CUGBP1 reduced cleavages of PARP and caspase
      3, cytotoxicity and subG1 population in BK10007S treated HepG2 cells. Overall,
      these findings provide scientific evidences that BK10007S induces apoptosis via
      inhibition of CUGBP1 and activation of caspases in hepatocellular carcinomas as a
      potent anticancer candidate.

PMID- 29036190
TI  - Clusternomics: Integrative context-dependent clustering for heterogeneous
      datasets.
AB  - Integrative clustering is used to identify groups of samples by jointly analysing
      multiple datasets describing the same set of biological samples, such as gene
      expression, copy number, methylation etc. Most existing algorithms for
      integrative clustering assume that there is a shared consistent set of clusters
      across all datasets, and most of the data samples follow this structure. However
      in practice, the structure across heterogeneous datasets can be more varied, with
      clusters being joined in some datasets and separated in others. In this paper, we
      present a probabilistic clustering method to identify groups across datasets that
      do not share the same cluster structure. The proposed algorithm, Clusternomics,
      identifies groups of samples that share their global behaviour across
      heterogeneous datasets. The algorithm models clusters on the level of individual
      datasets, while also extracting global structure that arises from the local
      cluster assignments. Clusters on both the local and the global level are modelled
      using a hierarchical Dirichlet mixture model to identify structure on both
      levels. We evaluated the model both on simulated and on real-world datasets. The
      simulated data exemplifies datasets with varying degrees of common structure. In
      such a setting Clusternomics outperforms existing algorithms for integrative and
      consensus clustering. In a real-world application, we used the algorithm for
      cancer subtyping, identifying subtypes of cancer from heterogeneous datasets. We
      applied the algorithm to TCGA breast cancer dataset, integrating gene expression,
      miRNA expression, DNA methylation and proteomics. The algorithm extracted
      clinically meaningful clusters with significantly different survival
      probabilities. We also evaluated the algorithm on lung and kidney cancer TCGA
      datasets with high dimensionality, again showing clinically significant results
      and scalability of the algorithm.

PMID- 29036191
TI  - Men ask more questions than women at a scientific conference.
AB  - Gender inequity in science and academia, especially in senior positions, is a
      recognised problem. The reasons are poorly understood, but include the
      persistence of historical gender ratios, discrimination and other factors,
      including gender-based behavioural differences. We studied participation in a
      professional context by observing question-asking behaviour at a large
      international conference with a clear equality code of conduct that prohibited
      any form of discrimination. Accounting for audience gender ratio, male attendees
      asked 1.8 questions for each question asked by a female attendee. Amongst only
      younger researchers, male attendees also asked 1.8 questions per female question,
      suggesting the pattern cannot be attributed to the temporary problem of
      demographic inertia. We link our findings to the 'chilly' climate for women in
      STEM, including wider experiences of discrimination likely encountered by women
      throughout their education and careers. We call for a broader and coordinated
      approach to understanding and addressing the barriers to women and other under
      represented groups. We encourage the scientific community to recognise the
      context in which these gender differences occur, and evaluate and develop methods
      to support full participation from all attendees.

PMID- 29036192
TI  - Viral infection upregulates myostatin promoter activity in orange-spotted grouper
      (Epinephelus coioides).
AB  - Myostatin is a negative regulator of myogenesis and has been suggested to be an
      important factor in the development of muscle wasting during viral infection. The
      objective of this study was to characterize the main regulatory element of the
      grouper myostatin promoter and to study changes in promoter activity due to viral
      stimulation. In vitro and in vivo experiments indicated that the E-box E6 is a
      positive cis-and trans-regulation motif, and an essential binding site for MyoD.
      In contrast, the E-box E5 is a dominant negative cis-regulatory. The
      characteristics of grouper myostatin promoter are similar in regulation of muscle
      growth to that of other species, but mainly through specific regulatory elements.
      According to these results, we conducted a study to investigate the effect of
      viral infection on myostatin promoter activity and its regulation. The nervous
      necrosis virus (NNV) treatment significantly induced myostatin promoter activity.
      The present study is the first report describing that specific myostatin motifs
      regulate promoter activity and response to viral infection.

PMID- 29036194
TI  - Micromeryx? eiselei-A new moschid species from Steinheim am Albuch, Germany, and
      the first comprehensive description of moschid cranial material from the Miocene
      of Central Europe.
AB  - Moschids are enigmatic pecoran ruminants whose phylogeny is still not fully
      understood. So far we know only little of the family's early evolutionary history
      and the origin of the modern genus, Moschus. Here we present a comprehensive
      description of cranial material, including the ear region and the dentition, of
      fossil moschid material from the Middle Miocene locality Steinheim am Albuch
      (13.5 Ma; Germany). This study provides the first exhaustive dataset for the
      cranial osteology of Micromeryx flourensianus, the most likely oldest true
      moschid. It furthermore reveals the presence of a second, so far undescribed
      moschid species, we here name Micromeryx? eiselei, in the abundant material from
      the locality. The two taxa can be clearly distinguished by characters of the
      skull, the ear region, the dentition, as well as by size. This evidences the
      sympatric occurrence of two moschid species in the locality Steinheim am Albuch.

PMID- 29036193
TI  - Gestational age-related patterns of AMOT methylation are revealed in preterm
      infant endothelial progenitors.
AB  - OBJECTIVE: Preterm birth is associated with altered angiogenesis and with
      increased risk of cardiovascular dysfunction and hypertension at adulthood. We
      previously demonstrated that in preterm newborns circulating cord blood
      endothelial progenitor cells (ECFC), responsible for angio/vasculogenesis, are
      reduced in number and display altered angiogenic properties. Altered angiogenic
      function was associated with a decreased expression of pro-angiogenic genes,
      among which the AMOT gene which is a strong positive regulator of angiogenesis.
      Such dysregulation may be related to epigenetic factors. In this study we analyse
      the methylation profiling of the AMOT gene during development, through a
      comparative analysis of the cord blood ECFC of preterm newborns and their term
      counterpart. METHODS: We used both cloning-sequencing and pyrosequencing
      experiments to perform a comparative analysis of the DNA methylation profile of
      the promoter CpG island of AMOT gene in the cord blood ECFC of 16 preterm
      newborns (28-35 weeks gestational age-GA) and 15 term newborns (>37 weeks GA).
      RESULTS: Twenty nine clones (obtained from 2 term newborns) and forty clones
      (obtained from 3 preterm newborns) were sequenced. The AMOT gene methylation rate
      was significantly higher in preterm compared to term newborns (4.5% versus 2.5%
      respectively: chi2 = 3.84; P = 1.8 10-02). Bisulfite pyrosequencing identified
      four CpG dinucleotides with significantly higher methylation levels in preterm
      newborns. This CpG-targeted methylation significantly decreased with increasing
      gestational age. CONCLUSIONS: These findings highlight importance of pro
      angiogenic AMOT gene methylation in ECFC, suggesting that epigenetic mechanisms
      may control the regulation of angiogenesis during development. Therefore they
      pave the way to specific short term and long term complications of preterm birth
      by altered angiogenesis.

PMID- 29036196
TI  - Understanding the antimicrobial activity of selected disinfectants against
      methicillin-resistant Staphylococcus aureus (MRSA).
AB  - Disinfectants and biocidal products have been widely used to combat Methicillin
      resistant Staphylococcus aureus (MRSA) infections in homes and healthcare
      environments. Although disruption of cytoplasmic membrane integrity has been
      documented as the main bactericidal effect of biocides, little is known about the
      biochemical alterations induced by these chemical agents. In this study, we used
      Fourier transform infrared (FT-IR) spectroscopy and chemometric tools as an
      alternative non-destructive technique to determine the bactericidal effects of
      commonly used disinfectants against MRSA USA-300. FTIR spectroscopy permits a
      detailed characterization of bacterial reactivity, allowing an understanding of
      the fundamental mechanism of action involved in the interaction between bacteria
      and disinfectants. The disinfectants studied were ethanol 70% (N = 5),
      isopropanol (N = 5), sodium hypochlorite (N = 5), triclosan (N = 5) and
      triclocarban (N = 5). Results showed less than 5% colony forming units growth of
      MRSA treated with triclocarban and no growth in the other groups. Nearly 70,000
      mid-infrared spectra from the five treatments and the two control (untreated; N =
      4) groups of MRSA (bacteria grown in TSB and incubated at 37 degrees C (Control
      I) / at ambient temperature (Control II), for 24h) were pre-processed and
      analyzed using principal component analysis followed by linear discriminant
      analysis (PCA-LDA). Clustering of strains of MRSA belonging to five treatments
      and the discrimination between each treatment and two control groups in MRSA
      (untreated) were investigated. PCA-LDA discriminatory frequencies suggested that
      ethanol-treated spectra are the most similar to isopropanol-treated spectra
      biochemically. Also reported here are the biochemical alterations in the
      structure of proteins, lipid membranes, and phosphate groups of MRSA produced by
      sodium hypochlorite, triclosan, and triclocarban treatments. These findings
      provide mechanistic information involved in the interaction between MRSA strains
      and hygiene products; thereby demonstrating the potential of spectroscopic
      analysis as an objective, robust, and label-free tool for evaluating the
      macromolecular changes involved in disinfectant-treated MRSA.

PMID- 29036195
TI  - Mutational and large deletion study of genes implicated in hereditary forms of
      primary hyperparathyroidism and correlation with clinical features.
AB  - The aim of this study was to carry out genetic screening of the MEN1, CDKN1B and
      AIP genes, both by direct sequencing of the coding region and multiplex ligation
      dependent probe amplification (MLPA) assay in the largest monocentric series of
      Italian patients with Multiple Endocrine Neoplasia type 1 syndrome (MEN1) and
      Familial Isolated Hyperparathyroidism (FIHP). The study also aimed to describe
      and compare the clinical features of MEN1 mutation-negative and mutation-positive
      patients during long-term follow-up and to correlate the specific types and
      locations of MEN1 gene mutations with onset and aggressiveness of the main MEN1
      manifestations. A total of 69 index cases followed at the Endocrinology Unit in
      Pisa over a period of 19 years, including 54 MEN1 and 15 FIHP kindreds were
      enrolled. Seven index cases with MEN1 but MEN1 mutation-negative, followed at the
      University Hospital of Cagliari, were also investigated. FIHP were also tested
      for CDC73 and CaSR gene alterations. MEN1 germline mutations were identified in
      90% of the index cases of familial MEN1 (F-MEN1) and in 23% of sporadic cases (S
      MEN1). MEN1 and CDC73 mutations accounted for 13% and 7% of the FIHP cohort,
      respectively. A CDKN1B mutation was identified in one F-MEN1. Two AIP variants of
      unknown significance were detected in two MEN1-negative S-MEN1. A MEN1 positive
      test best predicted the onset of all three major MEN1-related manifestations or
      parathyroid and gastro-entero-pancreatic tumors during follow-up. A comparison
      between the clinical characteristics of F and S-MEN1 showed a higher prevalence
      of a single parathyroid disease and pituitary tumors in sporadic compared to
      familial MEN1 patients. No significant correlation was found between the type and
      location of MEN1 mutations and the clinical phenotype. Since all MEN1 mutation
      positive sporadic patients had a phenotype resembling that of familial MEN1
      (multiglandular parathyroid hyperplasia, a prevalence of gastro-entero-pancreatic
      tumors and/or the classic triad) we might hypothesize that a subset of the
      sporadic MEN1 mutation-negative patients could represent an incidental
      coexistence of sporadic primary hyperparathyroidism and pituitary tumors or a
      MEN1 phenocopy, in our cohort, as in most cases described in the literature.

PMID- 29036197
TI  - Morphometric measurements of systemic atherosclerosis and visceral fat: Evidence
      from an autopsy study.
AB  - BACKGROUND: Morphometric measurements of systemic atherosclerosis and direct
      quantification of visceral fat are only possible using materials from autopsy
      studies. However, the few autopsy studies that have investigated the association
      of visceral fat with atherosclerosis had small sample sizes and focused on
      coronary arteries of young or middle-aged White subjects. We aimed to investigate
      the association of pericardial fat (PF) and abdominal visceral fat (AVF) with
      atherosclerosis in the aorta, coronary, carotid, and cerebral arteries in a large
      autopsy study. MATERIALS AND METHODS: We evaluated deceased subjects aged 30
      years or above. We dissected and weighted the PF and the AVF and evaluated the
      atherosclerotic burden in the aorta, as well as the carotid, coronary, and
      cerebral arteries using morphometric measurements. We also investigated the
      interaction of PF and AVF with age regarding the atherosclerotic burden. RESULTS:
      The mean age of the 240 included subjects was 64.8+/-15.3 years, and 63% was
      male. Greater PF was associated with a higher degree of aortic atherosclerosis
      after adjusting for confounding variables (coefficient = 4.39, 95% CI = 0.83;
      7.94, p = 0.02). Greater AVF was associated with a higher coronary stenosis index
      (coefficient = 1.49, 95% CI = 0.15; 2.83, p = 0.03) and a greater number of
      coronary plaques (coefficient = 0.71, 95% CI = 0.24; 1.19, p = 0.003). We did not
      find an association of PF or AVF with carotid or cerebral atherosclerotic burden.
      We found a significant interaction of AVF (coefficient = -0.08; 95% CI = -0.14; 
      0.02, p = 0.009) and PF (coefficient = -0.87, 95% CI = -1.70; -0.04, p = 0.04)
      with age regarding carotid artery atherosclerotic burden. CONCLUSIONS: Greater
      AVF was associated with greater atherosclerotic burden and extent in coronary
      arteries, while greater PF correlated with a higher degree of atherosclerosis in
      the aorta.

PMID- 29036199
TI  - The acute physiological stress response to driving: A systematic review.
AB  - BACKGROUND: The experience of driving has been suggested to be detrimental to
      health. One hypothesis is that each exposure elicits an acute stress response,
      and that repeated exposures may act as a chronic stressor. OBJECTIVE: The aim of
      this review is to evaluate and synthesise the evidence on whether driving elicits
      an acute physiological stress response. METHODS: Electronic databases, including
      CINAHL, PsycINFO and Medline, were searched for original articles written in
      English from database inception until March 2016. The inclusion criteria of this
      review included a quantitative examination of an acute physiological stress
      response to driving, in either on-road or simulated settings, compared to a
      comparison or control condition. This review followed the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting criteria.
      RESULTS: A total of 27,295 abstracts were screened and 28 full-text manuscripts
      retrieved. Of these, seven articles met the inclusion criteria including four
      simulator studies and three on-road studies. All suggested a significant change
      in at least one physiological outcome, but the strongest evidence was for
      increases in urine catecholamine and cortisol after driving for long hours on
      road; results on other outcomes are limited by the small number of studies or
      inconsistent findings. CONCLUSIONS: Overall, these studies provided moderate
      evidence to suggest that driving for long hours elicits a stress response over an
      extended period of time. There is insufficient evidence that driving for a
      shorter period of time elicits an acute stress response, especially in real, on
      road tasks. However, the limited number of studies, small sample sizes,
      heterogeneity in study objectives, methodologies and physiological outcomes limit
      conclusions. Future studies could be improved by recruiting a larger sample,
      utilizing modern stress markers such as heart rate variability, and primarily
      focusing on the acute physiological stress response to on-road driving.

PMID- 29036198
TI  - The homeodomain-interacting protein kinase HPK-1 preserves protein homeostasis
      and longevity through master regulatory control of the HSF-1 chaperone network
      and TORC1-restricted autophagy in Caenorhabditis elegans.
AB  - An extensive proteostatic network comprised of molecular chaperones and protein
      clearance mechanisms functions collectively to preserve the integrity and
      resiliency of the proteome. The efficacy of this network deteriorates during
      aging, coinciding with many clinical manifestations, including protein
      aggregation diseases of the nervous system. A decline in proteostasis can be
      delayed through the activation of cytoprotective transcriptional responses, which
      are sensitive to environmental stress and internal metabolic and physiological
      cues. The homeodomain-interacting protein kinase (hipk) family members are
      conserved transcriptional co-factors that have been implicated in both genotoxic
      and metabolic stress responses from yeast to mammals. We demonstrate that
      constitutive expression of the sole Caenorhabditis elegans Hipk homolog, hpk-1,
      is sufficient to delay aging, preserve proteostasis, and promote stress
      resistance, while loss of hpk-1 is deleterious to these phenotypes. We show that
      HPK-1 preserves proteostasis and extends longevity through distinct but
      complementary genetic pathways defined by the heat shock transcription factor
      (HSF-1), and the target of rapamycin complex 1 (TORC1). We demonstrate that HPK-1
      antagonizes sumoylation of HSF-1, a post-translational modification associated
      with reduced transcriptional activity in mammals. We show that inhibition of
      sumoylation by RNAi enhances HSF-1-dependent transcriptional induction of
      chaperones in response to heat shock. We find that hpk-1 is required for HSF-1 to
      induce molecular chaperones after thermal stress and enhances hormetic extension
      of longevity. We also show that HPK-1 is required in conjunction with HSF-1 for
      maintenance of proteostasis in the absence of thermal stress, protecting against
      the formation of polyglutamine (Q35::YFP) protein aggregates and associated
      locomotory toxicity. These functions of HPK-1/HSF-1 undergo rapid down-regulation
      once animals reach reproductive maturity. We show that HPK-1 fortifies
      proteostasis and extends longevity by an additional independent mechanism:
      induction of autophagy. HPK-1 is necessary for induction of autophagosome
      formation and autophagy gene expression in response to dietary restriction (DR)
      or inactivation of TORC1. The autophagy-stimulating transcription factors pha
      4/FoxA and mxl-2/Mlx, but not hlh-30/TFEB or the nuclear hormone receptor nhr-62,
      are necessary for extended longevity resulting from HPK-1 overexpression. HPK-1
      expression is itself induced by transcriptional mechanisms after nutritional
      stress, and post-transcriptional mechanisms in response to thermal stress.
      Collectively our results position HPK-1 at a central regulatory node upstream of
      the greater proteostatic network, acting at the transcriptional level by
      promoting protein folding via chaperone expression, and protein turnover via
      expression of autophagy genes. HPK-1 therefore provides a promising intervention
      point for pharmacological agents targeting the protein homeostasis system as a
      means of preserving robust longevity.

PMID- 29036200
TI  - The effect of the pathological V72I, D109N and T190M missense mutations on the
      molecular structure of alpha-dystroglycan.
AB  - Dystroglycan (DG) is a highly glycosylated protein complex that links the
      cytoskeleton with the extracellular matrix, mediating fundamental physiological
      functions such as mechanical stability of tissues, matrix organization and cell
      polarity. A crucial role in the glycosylation of the DG alpha subunit is played
      by its own N-terminal region that is required by the glycosyltransferase LARGE.
      Alteration in this O-glycosylation deeply impairs the high affinity binding to
      other extracellular matrix proteins such as laminins. Recently, three missense
      mutations in the gene encoding DG, mapped in the alpha-DG N-terminal region, were
      found to be responsible for hypoglycosylated states, causing congenital diseases
      of different severity referred as primary dystroglycanopaties.To gain insight on
      the molecular basis of these disorders, we investigated the crystallographic and
      solution structures of these pathological point mutants, namely V72I, D109N and
      T190M. Small Angle X-ray Scattering analysis reveals that these mutations affect
      the structures in solution, altering the distribution between compact and more
      elongated conformations. These results, supported by biochemical and biophysical
      assays, point to an altered structural flexibility of the mutant alpha-DG N
      terminal region that may have repercussions on its interaction with LARGE and/or
      other DG-modifying enzymes, eventually reducing their catalytic efficiency.

PMID- 29036201
TI  - Impact of social separation during pregnancy on the manifestation of defensive
      behaviors related to generalized anxiety and panic throughout offspring
      development.
AB  - The multiple insecurities, anatomical, physiological and psychological changes
      arising from the gestational period can generate an overload of stress in the
      mother and cause disturbances in the offspring, affecting it throughout its
      development. The existing analysis linking prenatal stress and offspring's
      anxiety have divergent results, being limited as to gestational week, type of
      stressor and age of progeny's assessment. Social separation has been described as
      a stressor that causes increase in anxiety. Thus, the present study evaluated the
      effects of social separation applied in one of the three gestational weeks of rat
      dams on the manifestation of the defensive behaviors related to generalized
      anxiety disorder and panic in the Elevated T Maze of the male progeny in three
      stages of development (1, 3 or 6 months of life). It was found, in the offspring
      of grouped (control) dams, increased behaviors associated with generalized
      anxiety disorder and a reduction of panic-like behaviors throughout development.
      For animals whose dams were socially separated during pregnancy, the most
      critical period of exposure was the 2nd gestational week, which affected the
      acquisition of aversive memory, demonstrated by the impairment on learning of
      avoidances of the offspring in all ages evaluated. Stressor exposure in this week
      also increased the avoidances, related to generalized anxiety of progeny in the
      1st month and decreased escapes, related to panic in the 3rd month of life and,
      at the age of 6 months old, an inverse situation, with the reduction of the
      defensive behaviors associated to generalized anxiety disorder. The results show
      that, when assessing effects of prenatal stress on the manifestation of anxiety,
      not only the period of exposure is important, but also the age of offspring
      assessed.

PMID- 29036203
TI  - Cooling the lower abdomen to reduce postpartum blood loss: A randomized
      controlled trial.
AB  - BACKGROUND: Cooling the lower abdomen is one of the Japanese traditional non
      pharmacological prophylactic managements for postpartum hemorrhage. This study
      aimed to evaluate the effectiveness of cooling the lower abdomen in reducing
      postpartum blood loss compared with no intervention. In both cases, women
      delivered vaginally without prophylactic oxytocin in the third stage of labor.
      METHODS: In this randomized controlled trial, the lower abdomen was cooled by
      placement of an 8.6 degrees C icepack during the first 2 h after placental
      delivery. The primary outcome was measured as the total blood loss within 2 h
      after delivery. This study had 80% power at the two tails of 5% significance
      level to detect the mean difference (MD, 70 g) in total blood loss within 2 h
      after delivery between the two groups. The sample size was calculated as 144
      women (72 women per group). RESULTS: Between January and May 2016, 160 women were
      randomly assigned to the intervention group (cooling the lower abdomen, n = 81)
      or the control group (n = 79). Baseline characteristics were similar between
      groups, with the exception of mean blood loss during the third stage of labor.
      The primary outcome was not reduced by cooling, compared with no intervention
      (mean blood loss, 513.3 vs. 478.1 g, respectively; MD = 35.2 g; 95% confidence
      interval = -65.3-135.7). No adverse events occurred; however, seven (8.7%) women
      in the intervention group declined to continue cooling the lower abdomen because
      of discomfort. CONCLUSION: Compared with the control group, cooling the lower
      abdomen did not reduce the total amount of blood loss up to 2 h after delivery.
      TRIAL REGISTRATION: UMIN-CTR UMIN000019834.

PMID- 29036202
TI  - Toxoplasma gondii induces FAK-Src-STAT3 signaling during infection of host cells
      that prevents parasite targeting by autophagy.
AB  - Targeting of Toxoplasma gondii by autophagy is an effective mechanism by which
      host cells kill the protozoan. Thus, the parasite must avoid autophagic targeting
      to survive. Here we show that the mammalian cytoplasmic molecule Focal Adhesion
      Kinase (FAK) becomes activated during invasion of host cells. Activated FAK
      appears to accompany the formation of the moving junction (as assessed by
      expression the parasite protein RON4). FAK activation was inhibited by approaches
      that impaired beta1 and beta3 integrin signaling. FAK caused activation of Src
      that in turn mediated Epidermal Growth Factor Receptor (EGFR) phosphorylation at
      the unique Y845 residue. Expression of Src-resistant Y845F EGFR mutant markedly
      inhibited ROP16-independent activation of STAT3 in host cells. Activation of FAK,
      Y845 EGFR or STAT3 prevented activation of PKR and eIF2alpha, key stimulators of
      autophagy. Genetic or pharmacologic inhibition of FAK, Src, EGFR phosphorylation
      at Y845, or STAT3 caused accumulation of the autophagy protein LC3 and LAMP-1
      around the parasite and parasite killing dependent on autophagy proteins (ULK1
      and Beclin 1) and lysosomal enzymes. Parasite killing was inhibited by expression
      of dominant negative PKR. Thus, T. gondii activates a FAK->Src->Y845-EGFR->STAT3
      signaling axis within mammalian cells, thereby enabling the parasite to survive
      by avoiding autophagic targeting through a mechanism likely dependent on
      preventing activation of PKR and eIF2alpha.

PMID- 29036204
TI  - Metabolic phenotyping in the mouse model of urinary tract infection shows that 3
      hydroxybutyrate in plasma is associated with infection.
AB  - Urinary tract infection is one of the most common bacterial infections worldwide.
      Current diagnosis of urinary tract infection chiefly relies on its clinical
      presentation, urine dipstick tests and urine culture. Small molecules found in
      bio-fluids related with both infection and recovery would facilitate diagnosis
      and management of UTI. Mass spectrometry-based fingerprinting of plasma and urine
      at 3 time points, pre-infection (t = -24h), infection (t = 24h) and post 3-day
      treatment (t = 112h), were acquired in the following four groups: mice which were
      healthy, infected but not treated, infected and treated with ciprofloxacin, and
      infected and treated with Relinqing(r) granules (n = 6 per group). A metabolomics
      workflow including multivariate analysis and ROC regression was employed to
      select metabolic features that correlated with UTI and its treatment. Circa 4,000
      molecular features were acquired for each sample. The small acid 3
      hydroxybutyrate in plasma was found to be differentiated for urinary tract
      infection, with an area under the curve = 0.97 (95% confidence interval: 0.93
      1.00, accuracy = 0.91, sensitivity = 0.92 and specificity = 0.91). The level of 3
      hydroxybutyrate in plasma was depleted after infection with a fold change of -22
      (q < 0.0001). Correlation between plasma 3-hydroxybutyrate and urine bacterial
      number in all groups and time points was r = -0.753 (p < 0.0001). The findings
      show that 3-hydroxybutyrate is depleted in blood and strongly associated with UTI
      at both infection and post-treatment stage in a UTI mouse model. Further work is
      envisaged to assess the clinical potential of blood tests to assist with UTI
      management.

PMID- 29036205
TI  - Characterization of microRNAs of Beta macrocarpa and their responses to Beet
      necrotic yellow vein virus infection.
AB  - Plant microRNAs (miRNAs) are a class of non-coding RNAs that play important roles
      in plant development, defense, and symptom development. Here, 547 known miRNAs
      representing 129 miRNA families, and 282 potential novel miRNAs were identified
      in Beta macrocarpa using small RNA deep sequencing. A phylogenetic analysis was
      performed, and 8 Beta lineage-specific miRNAs were identified. Through a
      differential expression analysis, miRNAs associated with Beet necrotic yellow
      vein virus (BNYVV) infection were identified and confirmed using a microarray
      analysis and stem-loop RT-qPCR. In total, 103 known miRNAs representing 38 miRNA
      families, and 45 potential novel miRNAs were differentially regulated, with at
      least a two-fold change, in BNYVV-infected plants compared with that of the mock
      inoculated control. Targets of these differentially expressed miRNAs were also
      predicted by degradome sequencing. These differentially expressed miRNAs were
      involved in hormone biosynthesis and signal transduction pathways, and enhanced
      axillary bud development and plant defenses. This work is the first to describe
      miRNAs of the plant genus Beta and may offer a reference for miRNA research in
      other species in the genus. It provides valuable information on the pathogenicity
      mechanisms of BNYVV.

PMID- 29036206
TI  - Risk characterization of hospitalizations for mental illness and/or behavioral
      disorders with concurrent heat-related illness.
AB  - BACKGROUND: Many studies have found significant associations between high ambient
      temperatures and increases in heat-related morbidity and mortality. Several
      studies have demonstrated that increases in heat-related hospitalizations are
      elevated among individuals with diagnosed mental illnesses and/or behavioral
      disorders (MBD). However, there are a limited number of studies regarding risk
      factors associated with specific mental illnesses that contribute, at least in
      part, to heat-related illnesses (HRI) in the United States. OBJECTIVE: To
      identify and characterize individual and environmental risk factors associated
      with MBD hospitalizations with a concurrent HRI diagnosis. METHODS: This study
      uses hospitalization data from the Nationwide Inpatient Sample (2001-2010).
      Descriptive analyses of primary and secondary diagnoses of MBDs with an HRI were
      examined. Risk ratios (RR) were calculated from multivariable models to identify
      risk factors for hospitalizations among patients with mental illnesses and/or
      behavioral disorders and HRI. RESULTS: Nondependent alcohol/drug abuse, dementia,
      and schizophrenia were among the disorders that were associated with increased
      frequency of HRI hospitalizations among MBD patients. Increased risk of MBD
      hospitalizations with HRI was observed for Males (RR, 3.06), African Americans
      (RR, 1.16), Native Americans (RR, 1.70), uninsured (RR, 1.92), and those 40 years
      and older, compared to MBD hospitalizations alone. CONCLUSIONS: Previous studies
      outside the U.S. have found that dementia and schizophrenia are significant risk
      factors for HRI hospitalizations. Our results suggest that hospitalizations among
      substance abusers may also be an important risk factor associated with heat
      morbidity. Improved understanding of these relative risks could help inform
      future public health strategies.

PMID- 29036207
TI  - Little Ice Age climatic erraticism as an analogue for future enhanced
      hydroclimatic variability across the American Southwest.
AB  - The American Southwest has experienced a series of severe droughts interspersed
      with strong wet episodes over the past decades, prompting questions about future
      climate patterns and potential intensification of weather disruptions under
      warming conditions. Here we show that interannual hydroclimatic variability in
      this region has displayed a significant level of non-stationarity over the past
      millennium. Our tree ring-based analysis of past drought indicates that the
      Little Ice Age (LIA) experienced high interannual hydroclimatic variability,
      similar to projections for the 21st century. This is contrary to the Medieval
      Climate Anomaly (MCA), which had reduced variability and therefore may be
      misleading as an analog for 21st century warming, notwithstanding its warm (and
      arid) conditions. Given past non-stationarity, and particularly erratic LIA, a
      'warm LIA' climate scenario for the coming century that combines high
      precipitation variability (similar to LIA conditions) with warm and dry
      conditions (similar to MCA conditions) represents a plausible situation that is
      supported by recent climate simulations. Our comparison of tree ring-based
      drought analysis and records from the tropical Pacific Ocean suggests that
      changing variability in El Nino Southern Oscillation (ENSO) explains much of the
      contrasting variances between the MCA and LIA conditions across the American
      Southwest. Greater ENSO variability for the 21st century could be induced by a
      decrease in meridional sea surface temperature gradient caused by increased
      greenhouse gas concentration, as shown by several recent climate modeling
      experiments. Overall, these results coupled with the paleo-record suggests that
      using the erratic LIA conditions as benchmarks for past hydroclimatic variability
      can be useful for developing future water-resource management and drought and
      flood hazard mitigation strategies in the Southwest.

PMID- 29036208
TI  - Transitioning couple's voluntary HIV counseling and testing (CVCT) from stand
      alone weekend services into routine antenatal and VCT services in government
      clinics in Zambia's two largest cities.
AB  - INTRODUCTION: Most HIV infections in Africa are acquired by married/cohabiting
      adults and WHO recommends couple's voluntary HIV counseling and testing (CVCT)
      for prevention. The handover from NGO-sponsored weekend CVCT to government
      sponsored services in routine weekday antenatal care (ANC) and individual
      voluntary testing and counseling (VCT) services in Zambia's two largest cities
      from 2009-2015 is described. METHODS: Government clinic counselors were trained
      to provide CVCT, and along with community health workers they promoted CVCT
      services in their clinic and surrounding areas. When client volume exceeded the
      capacity of on-duty staff in ANC and VCT, non-governmental organization (NGO)
      subsidies were offered for overtime pay. RESULTS: Implementation of routine CVCT
      services varied greatly by clinic and city. The 12 highest volume clinics were
      examined further, while 13 clinics had CVCT numbers that were too low to warrant
      further investigation. In Lusaka, the proportion of pregnant women whose partners
      were tested rose from 2.6% in 2009 to a peak of 26.2% in 2012 and 24.8% in 2015.
      Corresponding reports in Ndola were 2.0% in 2009, 17.0% in 2012 and 14.5% in
      2015. Obstacles to CVCT included: limited space and staffing, competing
      priorities, record keeping not adapted for couples, and few resources for
      promotion and increasing male involvement. Conflicting training models for
      'partner testing' with men and women separately vs. CVCT with joint post-test
      counseling led to confusion in reporting to district health authorities.
      DISCUSSION: A focused and sustained effort will be required to reach a meaningful
      number of couples with CVCT to prevent heterosexual and perinatal HIV
      transmission. Establishing targets and timelines, funding for dedicated and
      appropriately trained staff, adoption of standardized data recording instruments
      with couple-level indicators, and expansion of community and clinic-based
      promotions using proven models are recommended.

PMID- 29036209
TI  - Understanding differences in conception and abortion rates among under-20 year
      olds in Britain and France: Examining the contribution of social disadvantage.
AB  - OBJECTIVES: Socioeconomic status has been shown to be associated with sexual
      activity, contraceptive-use, pregnancy and abortion among young people. Less is
      known about whether the strength of the association differs for each outcome,
      between men and women, or cross-nationally. We investigate this using
      contemporaneous national probability survey data from Britain and France.
      METHODS: Data were analysed for 17-29 year-olds in Britain's third National
      Survey of Sexual Attitudes and Lifestyles (Natsal-3, n = 5959) undertaken 2010
      2012, and the 2010 French Fertility, Contraception and Sexual Dysfunction survey
      (FECOND, n = 3027). For each country, we estimated the gender-specific prevalence
      of sex before-16, contraceptive-use, conception before-20, and abortion in the
      event of conception, and used logistic regression to examine associations between
      two measures of socioeconomic status-educational-level and parental socioeconomic
      group-and each outcome. We tested for interactions between socioeconomic
      characteristics and country, and socioeconomic characteristics and gender, for
      each outcome. RESULTS: For each outcome, Britain and France differed with regard
      to prevalence but associations with socioeconomic characteristics were similar.
      Respondents of higher educational level, and, less consistently, with parents
      from higher socioeconomic-groups, were less likely to report sex before-16
      (Britain, men: adjusted OR (aOR) 0.5, women: aOR 0.5; France, men: aOR 0.5,
      women: aOR 0.5), no contraception at first sex (Britain, men: aOR 0.4, women: aOR
      0.6; France, men: aOR 0.4, women: aOR 0.4), pregnancy before-20 (Britain: aOR
      0.3; France: aOR 0.1), and in Britain, a birth rather than an abortion in the
      event of conception (Britain: aOR 3.1). We found no strong evidence of variation
      in the magnitude of the associations with socioeconomic characteristics by
      country or gender. CONCLUSIONS: Population level differences in conception and
      abortion rates between the two countries may partly be driven by the larger
      proportion of the population that is disadvantaged in Britain. This research
      highlights the role intra-country comparisons can play in understanding young
      people's sexual and reproductive behaviours.

PMID- 29036210
TI  - Isothermal amplification of environmental DNA (eDNA) for direct field-based
      monitoring and laboratory confirmation of Dreissena sp.
AB  - Loop-mediated isothermal amplification (LAMP) of aquatic invasive species
      environmental DNA (AIS eDNA) was used for rapid, sensitive, and specific
      detection of Dreissena sp. relevant to the Great Lakes (USA) basin. The method
      was validated for two uses including i) direct amplification of eDNA using a hand
      filtration system and ii) confirmation of the results after DNA extraction using
      a conventional thermal cycler run at isothermal temperatures. Direct
      amplification eliminated the need for DNA extraction and purification and allowed
      detection of target invasive species in grab or concentrated surface water
      samples, containing both free DNA as well as larger cells and particulates, such
      as veligers, eggs, or seeds. The direct amplification method validation was
      conducted using Dreissena polymorpha and Dreissena bugensis and uses up to 1 L
      grab water samples for high target abundance (e.g., greater than 10 veligers
      (larval mussels) per L for Dreissena sp.) or 20 L samples concentrated through 35
      MUm nylon screens for low target abundance, at less than 10 veligers per liter
      water. Surface water concentrate samples were collected over a period of three
      years, mostly from inland lakes in Michigan with the help of a network of
      volunteers. Field samples collected from 318 surface water locations included i)
      filtered concentrate for direct amplification validation and ii) 1 L grab water
      sample for eDNA extraction and confirmation. Though the extraction-based protocol
      was more sensitive (resulting in more positive detections than direct
      amplification), direct amplification could be used for rapid screening, allowing
      for quicker action times. For samples collected between May and August, results
      of eDNA direct amplification were consistent with known presence/absence of
      selected invasive species. A cross-platform smartphone application was also
      developed to disseminate the analyzed results to volunteers. Field tests of the
      direct amplification protocol using a portable device (Gene-Z) showed the method
      could be used in the field to obtain results within one hr (from sample to
      result). Overall, the direct amplification has the potential to simplify the eDNA
      based monitoring of multiple aquatic invasive species. Additional studies are
      warranted to establish quantitative correlation between eDNA copy number,
      veliger, biomass or organismal abundance in the field.

PMID- 29036211
TI  - Orally administered Taenia solium Calreticulin prevents experimental intestinal
      inflammation and is associated with a type 2 immune response.
AB  - Intestinal helminth antigens are inducers of type 2 responses and can elicit
      regulatory immune responses, resulting in dampened inflammation. Several
      platyhelminth proteins with anti-inflammatory activity have been reported. We
      have identified, cloned and expressed the Taenia solium calreticulin (rTsCRT) and
      shown that it predominantly induces a type 2 response characterized by IgG1, IL-4
      and IL-5 production in mice. Here, we report the rTsCRT anti-inflammatory
      activity in a well-known experimental colitis murine model. Mice were orally
      immunized with purified rTsCRT and colitis was induced with trinitrobenzene
      sulfonic acid (TNBS). Clinical signs of disease, macroscopic and microscopic
      tissue inflammation, cytokine production and micronuclei formation, as a marker
      of genotoxicity, were measured in order to assess the effect of rTsCRT
      immunization on experimentally induced colitis. rTsCRT administration prior to
      TNBS instillation significantly reduced the inflammatory parameters, including
      the acute phase cytokines TNF-alpha, IL-1beta and IL-6. Dampened inflammation was
      associated with increased local expression of IL-13 and systemic IL-10 and TGF
      beta production. Genotoxic damage produced by the inflammatory response was also
      precluded. Our results show that oral treatment with rTsCRT prevents excessive
      TNBS-induced inflammation in mice and suggest that rTsCRT has immunomodulatory
      properties associated with the expression of type 2 and regulatory cytokines
      commonly observed in other helminths.

PMID- 29036212
TI  - Dietary patterns and mental health after myocardial infarction.
AB  - BACKGROUND: Diet has been associated with better mental health in general
      populations, but less is known on this association in patients with a history of
      coronary heart disease. The objective of this study is to examine the cross
      sectional associations between dietary patterns and mental health in elderly
      patients with a history of myocardial infarction. METHODS: Data were drawn from
      the final assessment of the Alpha Omega cohort that monitored patients with a
      history of myocardial infarction (age range 60-80 years). 2171 patients with
      complete data for diet and mental health were included in this study. Diet was
      assessed with the 203-item Food Frequency Questionnaire, and subsequently
      categorized into two scores: the Dutch Healthy Nutrient and Food Score (DHNaFS)
      and the Dutch Undesirable Nutrient and Food Score (DUNaFS). Depressive symptoms,
      assessed with the Geriatric Depression Scale (GDS-15), and dispositional
      optimism, assessed with the 4-item questionnaire (4Q), were cross-sectionally
      analyzed in relation to dietary patterns using linear regression analysis.
      RESULTS: Patients were on average 72.2 years old and 79.5% were male. The DHNaFS
      score was associated with less depressive symptoms and higher dispositional
      optimism (beta = -0.108; P<0.001; and beta = 0.074; P<0.001), whereas no
      associations were found with the DUNaFS score. Particularly, consumption of
      vegetables, fruits, whole grains, fish, and low fat-dairy were associated with
      less depressive symptoms and higher optimism. Similar associations were found
      when analyzing the association between average DHNaFS score over the preceding 41
      months with depression beta = -0.085; P<0.001) and higher dispositional optimism
      (beta = 0.084; P<0.001). CONCLUSIONS: A healthy dietary pattern, in particular a
      higher consumption of vegetables, fruit, whole grains, fish and low-fat dairy,
      was associated with less depressive symptoms and higher optimism. However, given
      the cross-sectional nature of our analyses, our findings may also be explained by
      more optimistic participants making healthier food choices. Therefore, future
      prospective or interventions studies are needed to establish the direction of
      causality of this association. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT03192410.

PMID- 29036213
TI  - The value of real-time continuous glucose monitoring in premature infants of
      diabetic mothers.
AB  - To determine the feasibility of using a real-time continuous glucose monitoring
      system (RTGMS) in intensive care units, our study focus on preterm infants with
      diabetic mothers owing to their high risk of blood sugar abnormalities. Thirty
      preterm babies (M = 15 and F = 15; <= 36 week gestation age) were studied from
      within 72 hours of delivery. These babies were admitted to the newborn intensive
      care and were further categorized into groups based on whether their mothers with
      or without diabetic mellitus. Blood sugar levels were monitored by both RTGMS and
      the traditional intermittent arterial line (A-Line) glucose method. Continuous
      glucose monitoring were well tolerated in 30 infants. There were good consistency
      between RTGMS and A-Line glucose concentration measurements. Of the preterm
      infants, 33.33% experienced abnormal glucose levels (hypoglycemia or
      hyperglycemia) between the checkpoint intervals of the intermittent A-Line blood
      sugar measurements. RTGM showed advantages with regards to reduced pain, greater
      comfort, the provision of real-time information, high sensitivity (94.59%) and
      specificity (97.87%) in discovering abnormalities of blood sugar, which are
      especially valuable for premature infants of diabetic mothers. RTGMS is
      comparable to A-line measurement for identifying fluctuations in blood glucose in
      premature infants. RTGMS detects more episodes of abnormal glucose concentration
      than intermittent A-line blood glucose measurement. High risk infants, especially
      premature infants with diabetic mothers, should receive more intensive blood
      sugar level checks by using continuous RTGMS.

PMID- 29036214
TI  - The fate of endemic insects of the Andean region under the effect of global
      warming.
AB  - Three independent but complementary lines of research have provided evidence for
      the recognition of refugia: paleontology, phylogeography and species
      distributional modelling (SDM). SDM assesses the ecological requirements of a
      species based on its known occurrences and enables its distribution to be
      projected on past climatological reconstructions. One advantage over the other
      two approaches is that it provides an explicit link to environment and geography,
      thereby enabling the analysis of a large number of taxa in the search for more
      general refugia patterns. We propose a methodology for using SDM to recognize
      biogeographical patterns of endemic insects from Southern South America. We built
      species distributional models for 59 insect species using Maxent. The species
      analyzed in the study have narrow niche breadth and were classified into four
      assemblages according to the ecoregion they inhabit. Models were built for the
      Late Pleistocene, Mid-Holocene and Present. Through the procedure developed for
      this study we used the models to recognize: Late Pleistocene refugia; areas with
      high species richness during all three periods; climatically constant areas (in
      situ refugia); consistent patterns among in situ refugia, Pleistocene refugia and
      current distribution of endemic species. We recognized two adjacent Pleistocene
      refugia with distinct climates; four in situ refugia, some of which are
      undergoing a process of fragmentation and retraction or enlargement.
      Interestingly, we found a congruent pattern among in situ refugia, Pleistocene
      refugia and endemic species. Our results seem to be consistent with the idea that
      long-term climate stability is known to have a key role in promoting persistence
      of biodiversity in an area. Our Pleistocene and in situ refugia are consistent
      with refugia identified in studies focusing on different taxa and applying other
      methodologies, showing that the method developed can be used to identify such
      areas and prove their importance for conservation.

PMID- 29036215
TI  - Reduction of in utero lead exposures in South African populations: Positive
      impact of unleaded petrol.
AB  - BACKGROUND: Prenatal exposure to lead (Pb) has been shown to have negative and
      irreversible health impacts on foetal and early childhood development, affecting
      morbidity and mortality in adulthood. This study aimed to assess in utero Pb
      exposure, examine birth outcomes, and identify confounding factors in the large
      cohort of South African population, following the legislated removal of Pb from
      petrol. METHODS: Lead was measured in the maternal blood, urine and cord blood
      using Inductive Coupled Plasma Mass spectrometry (ICP-MS). The statistical
      analyses included Spearman's correlation, Wilcoxon rank sum (Mann Whitney),
      Kruskal-Wallis rank tests and multivariate linear regression. RESULTS: Overall,
      the geometric mean (GM) of Pb in maternal blood (PbB) was 1.32 MUg/dL (n = 640;
      95% CI, 1.24-1.40). In the subset cohort, the GM of paired maternal PbB and cord
      blood (PbC) was 1.73 MUg/dL (n = 350; 95% CI, 1.60-1.86) and 1.26 MUg/dL (n =
      317; 95% CI, 1.18-1.35), respectively with a positive correlation between the log
      PbB and the log PbC (rho = 0.65, p = <0.001). Birth outcomes showed geographical
      differences in the gestational age (p<0.001), birth length (p = 0.028) and head
      circumference (p<0.001), Apgar score at 5 min (p<0.001) and parity (p<0.002). In
      female neonates, a positive association was found between PbC and head
      circumference (rho = 0.243; p<0.016). The maternal PbB levels were positively
      correlated with race, educational status, water sources, cooking fuels and use of
      pesticides at home. CONCLUSIONS: This study has demonstrated not only the
      positive impact that the introduction of unleaded petrol and lead-free paint has
      had on in utero exposure to Pb in South Africa, but has also contributed new data
      on the topic, in a region where such data and scientific investigations in this
      field are lacking. Future research should evaluate if similar effects can be
      detected in young children and the adult population.

PMID- 29036216
TI  - Herpesviruses in etiopathogenesis of aggressive periodontitis: A meta-analysis
      based on case-control studies.
AB  - OBJECTIVE: Previous studies have found that herpesviruses are associated with
      aggressive periodontitis (AgP). However, these findings are controversial. This
      meta-analysis was aimed at clarifying the association between herpesviruses and
      AgP. METHODS: We identified eligible case-control studies evaluating the
      association between herpesviruses and AgP from PubMed and Embase databases in
      October 2015. Original data were extracted and quality assessment was done.
      Overall odds ratios (ORs) and 95% confidence intervals (CIs) were estimated.
      Random-effects model was determined. The stability was evaluated by sensitivity
      analysis. Finally, Egger's funnel plot was used to investigate the publication
      bias. RESULTS: Twelve case-control studies involving 322 patients and 342
      controls were included in the present meta-analysis. The included case-control
      studies were assessed as high quality. The quantitative synthesis results for
      Epstein-Barr virus (EBV) showed significance (10 studies: p = 0.0008, OR = 6.11,
      95% CI = 2.13-17.51); nevertheless, evidence of publication bias for EBV was
      considerable (EBV: Egger's test, p<0.001). Human cytomegalovirus (HCMV) and
      Herpes simplex virus type 1 (HSV-1) had significant association with AgP (12
      studies for HCMV: p = 0.009, OR = 3.63, 95% CI = 2.15-6.13; 4 studies for HSV-1:
      p<0.001, OR = 19.19, 95% CI = 4.16-79.06). Sensitivity analyses showed the
      results yielded consistency, and no significant publication bias was observed for
      HCMV. The association between Herpes simplex virus type 2 (HSV-2) and AgP was
      inconclusive (2 studies: p = 0.20, OR = 3.46, 95% CI = 0.51-23.51). CONCLUSION:
      This meta-analysis suggests that HCMV and HSV-1 are significantly associated with
      AgP. However, due to the heterogeneity among studies these conclusions should be
      cautiously interpreted. There is insufficient evidence to draw any conclusion
      between EBV, HSV-2 and AgP based on the currently limited data.

PMID- 29036218
TI  - Crystallographic and thermodynamic characterization of phenylaminopyridine
      bisphosphonates binding to human farnesyl pyrophosphate synthase.
AB  - Human farnesyl pyrophosphate synthase (hFPPS) catalyzes the production of the 15
      carbon isoprenoid farnesyl pyrophosphate. The enzyme is a key regulator of the
      mevalonate pathway and a well-established drug target. Notably, it was elucidated
      as the molecular target of nitrogen-containing bisphosphonates, a class of drugs
      that have been widely successful against bone resorption disorders. More
      recently, research has focused on the anticancer effects of these inhibitors. In
      order to achieve increased non-skeletal tissue exposure, we created
      phenylaminopyridine bisphosphonates (PNP-BPs) that have bulky hydrophobic side
      chains through a structure-based approach. Some of these compounds have proven to
      be more potent than the current clinical drugs in a number of antiproliferation
      assays using multiple myeloma cell lines. In the present work, we characterized
      the binding of our most potent PNP-BPs to the target enzyme, hFPPS. Co-crystal
      structures demonstrate that the molecular interactions designed to elicit tighter
      binding are indeed established. We carried out thermodynamic studies as well; the
      newly introduced protein-ligand interactions are clearly reflected in the
      enthalpy of binding measured, which is more favorable for the new PNP-BPs than
      for the lead compound. These studies also indicate that the affinity of the PNP
      BPs to hFPPS is comparable to that of the current drug risedronate. Risedronate
      forms additional polar interactions via its hydroxyl functional group and thus
      exhibits more favorable binding enthalpy; however, the entropy of binding is more
      favorable for the PNP-BPs, owing to the greater desolvation effects resulting
      from their large hydrophobic side chains. These results therefore confirm the
      overall validity of our drug design strategy. With a distinctly different
      molecular scaffold, the PNP-BPs described in this report represent an interesting
      new group of future drug candidates. Further investigation should follow to
      characterize the tissue distribution profile and assess the potential clinical
      benefits of these compounds.

PMID- 29036219
TI  - Correction: Role of mitochondrial DNA damage and dysfunction in veterans with
      Gulf War Illness.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0184832.].

PMID- 29036217
TI  - "ABC"-The Awareness-Body-Chart: A new tool assessing body awareness.
AB  - BACKGROUND: Despite the importance of body awareness for health and well-being
      there is still a lack of valid assessment tools to scan proper body awareness. To
      respond to the limitations of questionnaires (reading/interpretation problems)
      the Awareness-Body-Chart (ABC) was designed to assess body awareness by colouring
      51 regions according to their awareness. The objective of this study was to
      investigate the psychometric characteristics of the ABC. METHODS: In a
      questionnaire-study, 106 students in Graz (79 females, 27 males, age median 21
      (IQR 20-23) years) filled in the ABC, furthermore a German body awareness
      questionnaire "KEKS", and the Beck Depression Inventory II. Factor structure,
      internal consistency, and retest reliability of the ABC were investigated.
      Correlations of the ABC with the KEKS and the Beck Depression Inventory II and
      comparisons of subgroups were conducted. RESULTS: Through factor analyses, 14
      factors with clear assignments to body parts could be categorized: cranium, face,
      cervical/lumbar region, chest/abdomen, back, shoulder, upper arm, lower
      arm/elbow, hand, genital area, thigh/hip, knee, lower leg, and foot. The 14 body
      parts and the total score showed acceptable to high Cronbach's alphas (alpha =
      .64 - .97). The test-retest reliability showed values between rho = .71 and rho =
      .96. The correlation of the ABC and KEKS (r = .66, p < .001) confirmed validity.
      Further indications of validity could be seen in comparisons of subgroups and in
      correlations with the Beck Depression Inventory II. CONCLUSION: The ABC proved
      good psychometric properties with acceptable to high internal consistency,
      acceptable to high retest reliability and high construct validity. It is an easy
      to-use tool for clinical settings and research. The ABC opens new insights into
      body awareness-patterns of various subgroups.

PMID- 29036221
TI  - Retraction: Diabetes and Overexpression of proNGF Cause Retinal Neurodegeneration
      via Activation of RhoA Pathway.

PMID- 29036222
TI  - Lipid biomarker signatures as tracers for harmful cyanobacterial blooms in the
      Baltic Sea.
AB  - The recent proliferation of harmful cyanobacterial blooms (cyanoHABs) in the
      Baltic and other marginal seas poses a severe threat for the health of infested
      ecosystems as e.g. the massive export and decay of cyanobacterial biomass
      facilitates the spread of bottom water hypoxia. There is evidence that cyanoHABs
      occurred repeatedly in the Baltic Sea but knowledge of their spatiotemporal
      distribution and the cyanobacteria that contributed to them is limited. In this
      study, we examined representatives of the major bloom-forming heterocystous
      cyanobacteria (i.e. Aphanizomenon, Dolichospermum (formerly Anabaena) and
      Nodularia) to establish lipid fingerprints that allow tracking these
      environmentally important diazotrophs in the modern and past Baltic Sea. The
      distribution of normal and mid-chain branched alkanes, fatty acid methyl esters,
      bacteriohopanepolyols and heterocyst glycolipids permitted a clear chemotaxonomic
      separation of the different heterocystous cyanobacteria but also indicated a
      close phylogenetic relationship between representatives of the genera
      Aphanizomenon and Dolichospermum. Compared to the discontinuous nature of
      phytoplankton surveys studies, the distinct lipid profiles reported here will
      allow obtaining detailed spatiotemporal information on the frequency and
      intensity of Baltic Sea cyanoHABs as well as their community composition using
      the time-integrated biomarker signatures recorded in surface and subsurface
      sediments. As heterocystous cyanobacteria of the genera Aphanizomenon,
      Dolichospermum and Nodularia are generally known to form massive blooms in many
      brackish as well as lacustrine systems worldwide, the chemotaxonomic markers
      introduced in this study may allow investigating cyanoHABs in a great variety of
      contemporary environments from polar to tropical latitudes.

PMID- 29036220
TI  - Defective replication initiation results in locus specific chromosome breakage
      and a ribosomal RNA deficiency in yeast.
AB  - A form of dwarfism known as Meier-Gorlin syndrome (MGS) is caused by recessive
      mutations in one of six different genes (ORC1, ORC4, ORC6, CDC6, CDT1, and MCM5).
      These genes encode components of the pre-replication complex, which assembles at
      origins of replication prior to S phase. Also, variants in two additional
      replication initiation genes have joined the list of causative mutations for MGS
      (Geminin and CDC45). The identity of the causative MGS genetic variants strongly
      suggests that some aspect of replication is amiss in MGS patients; however,
      little evidence has been obtained regarding what aspect of chromosome replication
      is faulty. Since the site of one of the missense mutations in the human ORC4
      alleles is conserved between humans and yeast, we sought to determine in what way
      this single amino acid change affects the process of chromosome replication, by
      introducing the comparable mutation into yeast (orc4Y232C). We find that yeast
      cells with the orc4Y232C allele have a prolonged S-phase, due to compromised
      replication initiation at the ribosomal DNA (rDNA) locus located on chromosome
      XII. The inability to initiate replication at the rDNA locus results in
      chromosome breakage and a severely reduced rDNA copy number in the survivors,
      presumably helping to ensure complete replication of chromosome XII. Although
      reducing rDNA copy number may help ensure complete chromosome replication,
      orc4Y232C cells struggle to meet the high demand for ribosomal RNA synthesis.
      This finding provides additional evidence linking two essential cellular pathways
      DNA replication and ribosome biogenesis.

PMID- 29036223
TI  - Evaluation of blood-brain barrier function by quotient alpha2 macroglobulin and
      its relationship with interleukin-6 and complement component 3 levels in
      neuropsychiatric systemic lupus erythematosus.
AB  - Although quotient of alpha2 macroglobulin (Qalpha2MG) was previously reported to
      be useful for the evaluation of blood-brain barrier (BBB) function, it is not
      commonly used. We therefore evaluated BBB function among the various subsets of
      neuropsychiatric systemic lupus erythematosus (NPSLE) using quotient Q alpha2MG.
      Furthermore, we determined the correlation between Q alpha2MG and cerebrospinal
      (CSF) interleukin (IL)-6 level and quotient complement component 3 (Q C3). To
      determine intrathecal production of C3, the C3 index (Q C3/Q alpha2MG) was also
      calculated. Fifty-six patients with SLE were included in this study. Of these, 48
      were diagnosed with NPSLE, consisting of 30 diffuse NPSLE patients (acute
      confusional state (ACS): n = 14, non-ACS: n = 16) and 18 patients with focal
      NPSLE. CSF IL-6 concentration, and paired serum and CSF levels of alpha2MG and
      C3, were measured by enzyme-linked immuno solvent assay (ELISA). The Q alpha2MG,
      Q C3, and C3 index were then calculated. Q alpha2MG, Q C3, and IL-6
      concentrations in the CSF were significantly elevated in NPSLE compared with non
      NPSLE. Among the subsets of NPSLE, significant increases in Q alpha2MG, CSF IL-6,
      and Q C3 were observed in ACS compared with non-ACS or focal NPSLE. There was a
      positive correlation between CSF IL-6 level and Q alpha2MG, as well as between Q
      C3 and Q alpha2MG, in diffuse NPSLE. There were no significant differences in C3
      index between NPSLE and non-NPSLE, as well as among the subgroups of NPSLE. Our
      study suggests that BBB disruption is present in ACS, and elevated levels of IL-6
      and C3 in CSF in diffuse NPSLE, especially in ACS, might result from their entry
      to the CSF from the systemic circulation through the damaged BBB, as well as
      increased intrathecal production. Furthermore, Q alpha2MG might be useful for the
      evaluation of BBB integrity.

PMID- 29036224
TI  - Immortalized porcine mesenchymal cells derived from nasal mucosa, lungs, lymph
      nodes, spleen and bone marrow retain their stemness properties and trigger the
      expression of siglec-1 in co-cultured blood monocytic cells.
AB  - Mesenchymal stromal cells have been isolated from different sources. They are
      multipotent cells capable of differentiating into many different cell types,
      including osteocytes, chondrocytes and adipocytes. They possess a therapeutic
      potential in the management of immune disorders and the repair of damaged
      tissues. Previous work in our laboratory showed an increase of the percentages of
      CD172a+, CD14+, CD163+, Siglec-1+, CD4+ and CD8+ hematopoietic cells, when co
      cultured with immortalized mesenchymal cells derived from bone marrow. The
      present work aimed to demonstrate the stemness properties of SV40-immortalized
      mesenchymal cells derived from nasal mucosa, lungs, spleen, lymph nodes and red
      bone marrow and their immunomodulatory effect on blood monocytes. Mesenchymal
      cells from nasal mucosa, lungs, spleen, lymph nodes and red bone marrow were
      isolated and successfully immortalized using simian virus 40 large T antigen
      (SV40LT) and later, co-cultured with blood monocytes, in order to examine their
      differentiation stage (expression of Siglec-1). Flow cytometric analysis revealed
      that the five mesenchymal cell lines were positive for mesenchymal cell markers
      CD105, CD44, CD90 and CD29, but lacked the expression of myeloid cell markers
      CD16 and CD11b. Growth analysis of the cells demonstrated that bone marrow
      derived-mesenchymal cells proliferated faster compared with those derived from
      the other tissues. All five mesenchymal cell lines co-cultured with blood
      monocytes for 1, 2 and 7 days triggered the expression of siglec-1 in the
      monocytes. In contrast, no siglec-1+ cells were observed in monocyte cultures
      without mesenchymal cell lines. Mesenchymal cells isolated from nasal mucosa,
      lungs, spleen, lymph nodes and bone marrow were successfully immortalized and
      these cell lines retained their stemness properties and displayed
      immunomodulatory effects on blood monocytes.

PMID- 29036225
TI  - Human plasma-derived C1 esterase inhibitor concentrate has limited effect on
      house dust mite-induced allergic lung inflammation in mice.
AB  - C1 esterase inhibitor (C1-INH) can inhibit multiple pathways (complement, contact
      kinin, coagulation, and fibrinolysis) that are all implicated in the
      pathophysiology of asthma. We explored the effect of human plasma-derived C1-INH
      on allergic lung inflammation in a house dust mite (HDM) induced asthma mouse
      model by daily administration of C1-INH (15 U) during the challenge phase. NaCl
      and HDM exposed mice had comparable plasma C1-INH levels, while bronchoalveolar
      lavage fluid (BALF) levels were increased in HDM exposed mice coinciding with
      slightly reduced activation of complement (C5a). C1-INH treatment reduced Th2
      response and enhanced HDM-specific IgG1. Influx of eosinophils in BALF or lung,
      pulmonary damage, mucus production, procoagulant response or plasma leakage in
      BALF was similar in both groups. In conclusion, C1-INH dampens Th2 responses
      during HDM induced allergic lung inflammation.

PMID- 29036226
TI  - Structural plasticity of the N-terminal capping helix of the TPR domain of
      kinesin light chain.
AB  - Kinesin1 plays a major role in neuronal transport by recruiting many different
      cargos through its kinesin light chain (KLC). Various structurally unrelated
      cargos interact with the conserved tetratricopeptide repeat (TPR) domain of KLC.
      The N-terminal capping helix of the TPR domain exhibits an atypical sequence and
      structural features that may contribute to the versatility of the TPR domain to
      bind different cargos. We determined crystal structures of the TPR domain of both
      KLC1 and KLC2 encompassing the N-terminal capping helix and show that this helix
      exhibits two distinct and defined orientations relative to the rest of the TPR
      domain. Such a difference in orientation gives rise, at the N-terminal part of
      the groove, to the formation of one hydrophobic pocket, as well as to
      electrostatic variations at the groove surface. We present a comprehensive
      structural analysis of available KLC1/2-TPR domain structures that highlights
      that ligand binding into the groove can be specific of one or the other N
      terminal capping helix orientations. Further, structural analysis reveals that
      the N-terminal capping helix is always involved in crystal packing contacts,
      especially in a TPR1:TPR1' contact which highlights its propensity to be a
      protein-protein interaction site. Together, these results underline that the
      structural plasticity of the N-terminal capping helix might represent a
      structural determinant for TPR domain structural versatility in cargo binding.

PMID- 29036228
TI  - Factors associated to acceptable treatment adherence among children with chronic
      kidney disease in Guatemala.
AB  - Pediatric patients with Chronic Kidney Disease face several barriers to
      medication adherence that, if addressed, may improve clinical care outcomes. A
      cross sectional questionnaire was administered in the Foundation for Children
      with Kidney Disease (FUNDANIER, Guatemala City) from September of 2015 to April
      of 2016 to identify the predisposing factors, enabling factors and need factors
      related to medication adherence. Sample size was calculated using simple random
      sampling with a confidence level of 95%, confidence interval of 0.05 and a
      proportion of 87%. A total of 103 participants responded to the questionnaire
      (calculated sample size was 96). Independent variables were defined and
      described, and the bivariate relationship to dependent variables was determined
      using Odds Ratio. Multivariate analysis was carried out using logistic
      regression. The mean adherence of study population was 78% (SD 0.08, max = 96%,
      min = 55%). The mean adherence in transplant patients was 82% (SD 7.8, max 96%,
      min 63%), and the mean adherence in dialysis patients was 76% (SD 7.8 max 90%,
      min 55%). Adherence was positively associated to the mother's educational level
      and to higher monthly household income. Together predisposing, enabling and need
      factors illustrate the complexities surrounding adherence in this pediatric CKD
      population. Public policy strategies aimed at improving access to comprehensive
      treatment regimens may facilitate treatment access, alleviating economic strain
      on caregivers and may improve adherence outcomes.

PMID- 29036227
TI  - Evolution of hepatitis A virus seroprevalence among HIV-positive adults in
      Taiwan.
AB  - OBJECTIVES: The study aimed to describe the seroprevalence of hepatitis A virus
      (HAV) in HIV-positive adult patients in Taiwan between 2012 and 2016 and to
      examine the evolution of HAV seroprevalence between 2004-2007 and 2012-2016.
      METHODS: Clinical information and data of anti-HAV antibody results were
      collected from 2,860 antiretroviral-naive HIV-positive Taiwanese aged 18 years or
      older who initiated combination antiretroviral therapy at 11 hospitals around
      Taiwan between 2012 and 2016 (2012-2016 cohort). A multivariate logistic
      regression model was applied to identify independent variables associated with
      HAV seropositivity. Comparisons of HAV seroprevalences and associated clinical
      characteristics were made between this 2012-2016 cohort and a previous cohort of
      1580 HIV-positive patients in 2004-2007 (2004-2007 cohort). RESULTS: Of the 2,860
      HIV-positive patients between 2012 and 2016, the overall HAV seropositivity rate
      was 21.2% (605/2860), which was independently associated with an older age
      (adjusted odds ratio [AOR], per 1-year increase, 1.13; 95% confidence interval
      [95% CI], 1.11-1.15) and co-infection with hepatitis B virus (AOR 1.44; 95% CI,
      1.08-1.93). Residence in southern Taiwan (AOR 0.49; 95% CI, 0.34-0.72) was
      inversely associated with HAV seropositivity. The overall HAV seroprevalence in
      the 2012-2016 cohort was significantly lower than that in the 2004-2007 cohort
      (21.2% vs 60.9%, p<0.01). The decreases of HAV seropositivity rate were observed
      in nearly every age-matched group, which suggested the cohort effect on HAV
      seroepidemiology. However, among individuals aged 25 years or younger, the HAV
      seropositivity rate increased from 3.8% (2/52) in the 2004-2007 cohort to 8.5%
      (50/587) in the 2012-2016 cohort, with 95.4% (560/587) being MSM in this age
      group of the latter cohort. CONCLUSIONS: HAV seroprevalence has decreased with
      time among HIV-positive adults in Taiwan. The cohort effect has increased the
      number of young HIV-positive patients that are susceptible to HAV infection in a
      country without nationwide childhood vaccination program against HAV.

PMID- 29036229
TI  - Cloning and characterization of the Cerasus humilis sucrose phosphate synthase
      gene (ChSPS1).
AB  - Sucrose is crucial to the growth and development of plants, and sucrose phosphate
      synthase (SPS) plays a key role in sucrose synthesis. To understand the genetic
      and molecular mechanisms of sucrose synthesis in Cerasus humilis, ChSPS1, a
      homologue of SPS, was cloned using RT-PCR. Sequence analysis showed that the open
      reading frame (ORF) sequence of ChSPS1 is 3174 bp in length, encoding a predicted
      protein of 1057 amino acids. The predicted protein showed a high degree of
      sequence identity with SPS homologues from other species. Real-time RT-PCR
      analysis showed that ChSPS1 mRNA was detected in all tissues and the
      transcription level was the highest in mature fruit. There is a significant
      positive correlation between expression of ChSPS1 and sucrose content.
      Prokaryotic expression of ChSPS1 indicated that ChSPS1 protein was expressed in
      E. coli and it had the SPS activity. Overexpression of ChSPS1 in tobacco led to
      upregulation of enzyme activity and increased sucrose contents in transgenic
      plants. Real-time RT-PCR analysis showed that the expression of ChSPS1 in
      transgenic tobacco was significantly higher than in wild type plants. These
      results suggested that ChSPS1 plays an important role in sucrose synthesis in
      Cerasus humilis.

PMID- 29036230
TI  - Predictors of adverse drug reaction-related hospitalisation in Southwest
      Ethiopia: A prospective cross-sectional study.
AB  - BACKGROUND: Adverse drug reactions (ADRs) are important causes of morbidity and
      mortality in the healthcare system; however, there are no studies reporting on
      the magnitude and risk factors associated with ADR-related hospitalisation in
      Ethiopia. OBJECTIVES: To characterise the reaction types and the drugs implicated
      in admission to Jimma University Specialized Hospital, Southwest Ethiopia, and to
      identify risk factors associated with ADR-related hospitalisation. METHODS: A
      prospective cross-sectional study was conducted from May 2015 to August 2016
      among consenting patients aged >=18 years consecutively admitted to medical wards
      taking at least one medication prior to admission. ADR-related hospitalisations
      were determined through expert review of medical records, laboratory tests,
      patient interviews and physical observation. ADR causality was assessed by the
      Naranjo algorithm followed by consensus review with internal medicine specialist.
      ADR preventability was assessed using Schumock and Thornton's criteria. Only
      definite and probable ADRs that provoked hospitalisation were considered. Binary
      logistic regression was used to identify independent predictors of ADR-related
      hospitalisation. RESULTS: Of 1,001 patients, 103 (10.3%) had ADR-related
      admissions. Common ADRs responsible for hospitalisation were hepatotoxicity (35,
      29.4%) and acute kidney injury (27, 22.7%). The drug classes most frequently
      implicated were antitubercular agents (45, 25.0%) followed by antivirals (22,
      12.2%) and diuretics (19, 10.6%). Independent predictors of ADR-related
      hospitalisation were body mass index (BMI) <18.5 kg/m2 (adjusted odd ratio [AOR]
      = 1.69; 95% confidence interval [CI] = 1.10-2.62; p = 0.047), pre-existing renal
      disease (AOR = 2.84; 95%CI = 1.38-5.85, p = 0.004), pre-existing liver disease
      (AOR = 2.61; 95%CI = 1.38-4.96; p = 0.003), number of comorbidities >=4 (AOR =
      2.09; 95%CI = 1.27-3.44; p = 0.004), number of drugs >=6 (AOR = 2.02; 95%CI =
      1.26-3.25; p = 0.004) and history of previous ADRs (AOR = 24.27; 95%CI = 11.29
      52.17; p<0.001). Most ADRs (106, 89.1%) were preventable. CONCLUSIONS: ADRs were
      a common cause of hospitalisation. The majority of ADRs were preventable,
      highlighting the need for monitoring and review of patients with lower BMI, ADR
      history, renal and liver diseases, multiple comorbidities and medications. ADR
      predictors should be integrated into clinical pathways and pharmacovigilance
      systems.

PMID- 29036231
TI  - Vildagliptin increases butyrate-producing bacteria in the gut of diabetic rats.
AB  - Emerging evidence supports a key role for the gut microbiota in metabolic
      diseases, including type 2 diabetes (T2D) and obesity. The dipeptidyl peptidase-4
      inhibitor vildagliptin is highly efficacious in treating T2D. However, whether
      vildagliptin can alter the gut microbiome is still unclear. This study aimed to
      identify whether vildagliptin modifies the gut microbiota structure during T2D
      treatment. Diabetic Sprague-Dawley (SD) rats were induced by a high-fat diet and
      streptozotocin injection (HFD/STZ). Diabetic rats were orally administered a low
      dose of vildagliptin (LV, 0.01 g/kg/d vildagliptin), high dose of vildagliptin
      (HV, 0.02 g/kg/d vildagliptin), or normal saline for 12 weeks. Fasting blood
      glucose, blood glucose after glucose loading, and serum insulin levels were
      significantly reduced in the LV and HV groups compared with those in the T2D
      group. The serum GLP-1 level increased more in the vildagliptin-treated group
      than in the T2D group. Pyrosequencing of the V3-V4 regions of 16S rRNA genes
      revealed that vildagliptin significantly altered the gut microbiota. The
      operational taxonomic units (OTUs) and community richness (Chao1) index were
      significantly reduced in the vildagliptin and diabetic groups compared with those
      in the control group. At the phylum level, a higher relative abundance of
      Bacteroidetes, lower abundance of Firmicutes, and reduced ratio of
      Fimicutes/Bacteroidetes were observed in the vildagliptin-treated group.
      Moreover, vildagliptin treatment increased butyrate-producing bacteria, including
      Baceroides and Erysipelotrichaeae, in the diabetic rats. Moreover, Lachnospira
      abundance was significantly negatively correlated with fasting blood glucose
      levels. In conclusion, vildagliptin treatment could benefit the communities of
      the gut microbiota.

PMID- 29036233
TI  - Correction: Diabetes-Induced Superoxide Anion and Breakdown of the Blood-Retinal
      Barrier: Role of the VEGF/uPAR Pathway.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0071868.].

PMID- 29036232
TI  - Rare and common variants of APOB and PCSK9 in Korean patients with extremely low
      low-density lipoprotein-cholesterol levels.
AB  - BACKGROUND: Screening of variants, related to lipid metabolism in patients with
      extreme cholesterol levels, is a tool used to identify targets affecting
      cardiovascular outcomes. The aim of this study was to examine the prevalence and
      characteristics of rare and common variants of APOB and PCSK9 in Korean patients
      with extremely low low-density lipoprotein-cholesterol (LDL-C) levels. METHODS:
      Among 13,545 participants enrolled in a cardiovascular genome cohort, 22
      subjects, whose LDL-C levels without lipid-lowering agents were <=1 percentile
      (48 mg/dL) of Korean population, were analyzed. Two target genes, APOB and PCSK9,
      were sequenced by targeted next-generation sequencing. Prediction of functional
      effects was conducted using SIFT, PolyPhen-2, and Mutation Taster, and matched
      against a public database of variants. RESULTS: Eight rare variants of the two
      candidate genes (five in APOB and three in PCSK9) were found in nine subjects.
      Two subjects had more than two different rare variants of either gene (one
      subject in APOB and another subject in APOB/PCSK9). Conversely, 12 common
      variants (nine in APOB and three in PCSK9) were discovered in 21 subjects. Among
      all variants, six in APOB and three in PCSK9 were novel. Several variants
      previously reported functional, including c.C277T (p.R93C) and c.G2009A (p.G670E)
      of PCSK9, were found in our population. CONCLUSIONS: Rare variants of APOB or
      PCSK9 were identified in nine of the 22 study patients with extremely low LDL-C
      levels, whereas most of them had common variants of the two genes. The common
      novelty of variants suggested polymorphism of the two genes among them. Our
      results provide rare genetic information associated with this lipid phenotype in
      East Asian people.

PMID- 29036234
TI  - [Radiolucent and opaque lesions on a panoramic radiograph; a cyst or not?]
AB  - In the context of pain diagnostics, several lesions, partially radiolucent and
      partially opaque, were identified by chance in the mandible and maxilla. On the
      basis of the characteristic x-ray image, it was assumed to be cemento-osseous
      dysplasia. At an early stage, this cannot easily be distinguished from apical
      periodontitis. An incorrect diagnosis could lead to needless endodontic
      treatment.

PMID- 29036235
TI  - [Medicaments and oral healthcare 5. Adverse effects of -medications and over-the
      counter drugs on teeth].
AB  - Intrinsic tooth discoloration may occur as an adverse effect of fluoride and
      tetracyclines. Extrinsic tooth discoloration may occur as superficial staining or
      as discoloration of the superficial pellicle and/or biofilm due to chlorhexidine,
      liquid iron salts, essential oils, some antibiotics and stannous fluoride.
      Inhibition of orthodontic tooth movement has been reported due to the use of
      prostaglandin synthetase inhibitors. If medications or over-the-counter drugs
      induce hyposalivation or contain much sucrose, caries may develop. Erosion may
      occur if the acidity of medications or over-the-counter drugs is excessive.
      Attrition is a well-known adverse effect of serotonin reuptake inhibitors,
      antiparkinson agents, and antipsychotics. Congenital dysplasia is observed
      following childhood treatment with cytostatic drugs. External cervical root
      resorption is an adverse effect of internal teeth-whitening products. Prenatal
      exposure to antiepileptic drugs and childhood treatment with cytostatic drugs may
      cause dental agenesis. Antiseptic drugs applied for external teeth-whitening and
      toothpastes with additional ingredients to prevent extrinsic discoloration and
      creation of calculus, may cause tooth hypersensitivity.

PMID- 29036236
TI  - [Preventive dentistry 8. Diet and caries].
AB  - The call to consume less sugar in order to improve the general health is becoming
      increasingly loud. The question is in what way consuming less sugar could also
      contribute to a lower risk of caries. This can be achieved by limiting the
      frequency of consuming sugary snacks. For oral health reasons, people in the
      Netherlands are advised not to consume things containing sugar more than four
      times between meals. Another way to make the diet less cariogenic is to
      substitute sugar in foods by non-caloric intense sweeteners, caloric sugar
      alcohols or 'new carbohydrates'. Non-caloric intense sweeteners and caloric
      sweeteners have been proven to be non-cariogenic. New carbohydrates still have to
      be individually tested.

PMID- 29036237
TI  - [Priorities and recommendations in oral health care for older people].
AB  - The oral health of older people in the Netherlands, especially those who are
      vulnerable and dependent on care, is insufficient. Older people and other
      stakeholders participated in a so-called Priority Setting Partnership study to
      identify hindrances that have been experienced in oral health care and to distil
      from their experience items for the agenda for further research. For this reason,
      discussions were held in 5 focus groups with respectively 1 group of older
      people, caregivers, external parties and health care professionals. In a fifth
      focus group, a so-called 'consensus group', the definitive list of prioritised
      items on the agenda was formulated. The most important priorities concern policy
      and organisation of oral health care, awareness, cooperation among various health
      care professionals, the financing and organisation of oral health care for older
      people living at home and education concerning oral health care for all health
      care professionals. Awareness about the importance of good oral health for older
      people among health care professionals is the first step towards better oral
      health care for older people in the Netherlands.

PMID- 29036238
TI  - [A PhD completed. Periodontitis, diabetes mellitus, cardiovascular disease: a
      Bermuda triangle].
AB  - The relationship among periodontitis, diabetes mellitus and atherosclerotic
      cardiovascular disease is complex and can be thought of as a Bermuda triangle. A
      relationship has been demonstrated between periodontitis, a worsening in the
      condition of the vascular system and an increased total level of inflammatory
      markers. Patients with severe periodontitis also show raised levels of
      glycosylated haemoglobin. This means that severe periodontitis can be an early
      indication of diabetes mellitus. Periodontal treatment generally promotes
      improved blood sugar regulation in diabetes patients, an improved condition of
      the vascular system and a decrease in the total levels of inflammation. Factors
      such as genetics, lifestyle and the presence of other chronic co-morbidities
      contribute to the complexity of this relationship. For the treatment of severe
      periodontitis, interdisciplinary cooperation among dentists, general
      practitioners and internists is therefore recommended.

PMID- 29036239
TI  - [A PhD completed. Factors subjectively and objectively influencing children's
      need for orthodontic treatment and their related quality of life].
AB  - Oral health can be measured from the perspective of the professional
      (objectively) and from the perspective of the patient (subjectively). However,
      objective and subjective oral health do not match well. The focus of this
      research, then, is the relationship between objective oral health, subjective
      oral health and oral health-related quality of life (OHRQoL) in children. These
      relationships were considered in connection with orthodontic problems. The
      research was carried out as part of the Generation R Study, a prospective study
      of the health of 10,000 children in Rotterdam, the Netherlands. Besides
      malocclusions and caries, several non-clinical factors, such as environmental
      factors and personal qualities, seemed to have an influence on the subjective
      need for orthodontic treatment and OHRQoL. Age, gender, ethnicity, and a feeling
      of self-worth are just like socio-economic factors that result in a variable
      relationship between subjective and objective oral health. This knowledge cannot
      only help to support effective communication between professional and patient,
      but also to develop targeted interventions to promote children's oral health.

PMID- 29036248
TI  - Apremilast and Narrowband Ultraviolet-B Combination Therapy for Treating Moderate
      to-Severe Plaque Psoriasis.
AB  - BACKGROUND: Combining narrowband UVB (NB-UVB) phototherapy with biologics has
      been shown to enhance the therapeutic response of plaque psoriasis patients. The
      objective of this study was to evaluate the effectiveness of apremilast combined
      with NB-UVB in patients with moderate to severe plaque psoriasis. METHODS: This
      was a 12-week, open-label study of 29 patients diagnosed with moderate to severe
      psoriasis. Patients received apremilast 30 mg twice daily, and increasing doses
      of NB-UVB (310-312 nm) 3 times per week for 12 weeks. RESULTS: Twenty-two of 29
      patients (76%) completed the 12-week apremilast and NB-UVB combination therapy;
      73% (16 of 22 completers) achieved a PASI 75 response at week 12. Mean scores for
      PASI, VAS pain, VAS itch, DLQI, and PGA improved by 77%, 77%, 69%, 70%, and 67%,
      respectively, at week 12. The most commonly reported adverse events (AEs) were
      mild and moderate first-degree burns related to NB-UVB (n=11 [38%] patients). A
      second-degree NB-UVB burn was reported (likely due to an underlying
      photosensitivity) and was considered a serious AE. CONCLUSION: The combination of
      apremilast with NB-UVB was effective for the treatment of moderate to severe
      plaque psoriasis, without any unexpected safety signals. Apremilast combined with
      NB-UVB provided a high treatment response in patients with moderate to severe
      plaque psoriasis, and may be an option for patients to enhance a patient's
      initial therapeutic response. <p><em>J Drugs Dermatol. 2017;16(10):957
      962.</em></p>.

PMID- 29036249
TI  - Cost-Effectiveness Analysis of Ixekizumab vs Etanercept and Their Manufacturer
      Recommended Dosing Regimens in Moderate to Severe Plaque Psoriasis.
AB  - INTRODUCTION: Biologic therapies have revolutionized the treatment of psoriasis;
      however, their use is limited by costs. Ixekizumab was more effective than
      etanercept in the UNCOVER trials, and the Food and Drug Administration (FDA)
      approved ixekizumab for treating psoriasis. Evaluating the cost-effectiveness of
      these therapies is crucial for medical decision making and our objective was to
      determine the cost-effectiveness of various ixekizumab dosing frequencies
      compared with etanercept. METHODS: We utilized published data from the UNCOVER
      comparative efficacy trials, including transitional probabilities and treatment
      response rates, to create a Markov model simulating the clinical course and cost
      effectiveness of three treatment algorithms for patients with moderate to severe
      plaque psoriasis over 60-weeks: (1) ixekizumab every 2 weeks for 12 weeks then
      every 4 weeks, (2) ixekizumab every 4 weeks throughout the treatment period, (3)
      biweekly etanercept for 12 weeks then once weekly. We utilized a standard
      willingness-to-pay (WTP) threshold of $150,000 per quality adjusted life year
      (QALY) and Medicaid drug acquisition costs for our calculations. RESULTS:
      Ixekizumab every 4 weeks was $28,681 (USD) less expensive than biweekly
      etanercept, and $21,375 less expensive, and 0.006 QALY less effective, than
      ixekizumab every 2 weeks-- a savings of $28.7 and $21.4 million, respectively,
      per 1,000 patients. A 95.6% cost reduction to $197.83 per dose is required for
      ixekizumab every 2 weeks to be more cost-effective than every 4 weeks. Biweekly
      etanercept requires a 29.5% cost reduction ($743.82 per dose) to be competitive
      with ixekizumab every 4 weeks. DISCUSSION: This cost-effectiveness model utilizes
      strong input data but is a limited approximation of real-life scenarios.
      Treatment with ixekizumab every 2 weeks is unlikely to be cost-effective compared
      with ixekizumab every 4 weeks at current U.S. market prices. Yet, the U.S. FDA
      approval and manufacturer's recommendation are for ixekizumab every 2 weeks.
      Accordingly, we suggested selecting biologic therapies using cost-effectiveness
      analyses. <p><em>J Drugs Dermatol. 2017;16(10):964-970.</em></p>.

PMID- 29036250
TI  - A Randomized, Double-Blind, Placebo-Controlled Study of the Vasoconstrictor
      Potency of Topical 0.25% Desoximetasone Spray: A High to Super High Range of
      Potency (Class I to Class II) Corticosteroid Formulation.
AB  - BACKGROUND: Topical corticosteroids offer great efficacy in controlling a wide
      variety of dermatoses. Traditional ointment vehicles are messy and difficult to
      apply, which might limit adherence. Alternative vehicle formulations such as
      topical sprays might improve adherence due to their ease of application. The
      potency of desoximetasone spray is not fully characterized. OBJECTIVE: To
      evaluate the relative vasoconstrictive potency of desoximetasone 0.25% topical
      spray formulation. METHODS: This is a randomized, blinded, single-center study
      comparing the vasoconstrictive properties of desoximetasone 0.25% topical spray
      to placebo and seven other known potency topical corticosteroid formulations. The
      primary endpoint was the degree of vasoconstriction measured using a colorimeter
      device. RESULTS: Thirty-two healthy subjects met eligibility criteria.
      Desoximetasone 0.25% topical spray (REGWQ Grouping = A) showed a trend toward
      greater vasoconstrictive potency compared to clobetasol propionate 0.05% spray
      (REGWQ Grouping = A). No adverse or serious events were reported. LIMITATIONS:
      The trial enrolled 90% females, which may affect the external validity of the
      study. Different populations may respond differently to desoximetasone spray.
      CONCLUSIONS: Desoximetasone 0.25% topical spray is a high to super high range of
      potency (Class I to Class II) steroid formulation. Given the cosmetic
      acceptability of spray products, we anticipate that this type of product would be
      highly effective for the treatment of inflammatory diseases in clinical practice.
      <p><em>J Drugs Dermatol. 2017;16(10):972-975.</em></p>.

PMID- 29036251
TI  - An Adhesive Patch-Based Skin Biopsy Device for Molecular Diagnostics and Skin
      Microbiome Studies.
AB  - INTRODUCTION: A number of diagnoses in clinical dermatology are currently
      histopathologically confirmed and this image recognition-based confirmation
      generally requires surgical biopsies. The increasing ability of molecular
      pathology to corroborate or correct a clinical diagnosis based on objective gene
      expression, mutation analysis, or molecular microbiome data is on the horizon and
      would be further supported by a tool or procedure to collect samples non
      invasively. This study characterizes such a tool in form of a 'bladeless'
      adhesive patch-based skin biopsy device. METHODS: The performance of this device
      was evaluated through a variety of complementary technologies including
      assessment of sample biomass, electron microscopy demonstrating the harvesting of
      layers of epidermal tissue, and isolation of RNA and DNA from epidermal skin
      samples. Samples were obtained by application of adhesive patches to the
      anatomical area of interest. RESULTS: Biomass assessment demonstrated collection
      of approximately 0.3mg of skin tissue per adhesive patch and electron microscopy
      confirmed the nature of the harvested epidermal skin tissue. The obtained tissue
      samples are stored in a stable fashion on adhesive patches over a wide range of
      temperatures (-80oC to +60oC) and for extended periods of time (7 days or more).
      Total human RNA, human genomic DNA and microbiome DNA yields were 23.35 +
      15.75ng, 27.72 + 20.71ng and 576.2 + 376.8pg, respectively, in skin samples
      obtained from combining 4 full patches collected non-invasively from the forehead
      of healthy volunteers. DISCUSSION: The adhesive patch skin sampling procedure is
      well tolerated and provides robust means to obtain skin tissue, RNA, DNA, and
      microbiome samples without involving surgical biopsies. The non-invasively
      obtained skin samples can be shipped cost effectively at ambient temperature by
      mail or standard courier service, and are suitable for a variety of molecular
      analyses of the skin microbiome as well as of keratinocytes, T cells, dendritic
      cells, melanocytes, and other skin cells involved in the pathology of various
      skin conditions and conditions where the skin can serve as a surrogate target
      organ. <p><em>J Drugs Dermatol. 2017;16(10):979-986.</em></p>.

PMID- 29036252
TI  - Efficacy of Isotretinoin and Acitretin in Treatment of Frontal Fibrosing
      Alopecia: Retrospective Analysis of 54 Cases.
AB  - This study aimed to assess the efficacy of systemic retinoids in treating frontal
      fibrosing alopecia (FFA). It was based on a retrospective analysis of 54 female
      patients with FFA treated with: oral isotretinoin at the daily dose of 20 mg
      (29/54) or acitretin at the daily dose of 20 mg (11/54) or with oral finasteride
      5 mg/daily (14/54). The study was conducted between 2007 and 2017. The basic of
      the study is the measurement of distance between the frontal hairline and the
      glabellar crease prior to the commencement of treatment and after 6, 12, and 24
      months. The treatment with systemic retinoids lasted between 12 and 16 months
      (the mean duration of treatment was 13.5 months). The primary treatment goal was
      defined as no further progression of disease after 12 months of treatment, while
      the secondary treatment goal was defined as no further progression of disease
      following the discontinuation of systemic retinoids. The primary treatment goal
      was achieved by 76% (23/29) of patients treated with isotretinoin, 73% (8/11) of
      patients treated with acitretin, and 43% (6/14) of patients treated with
      finasteride. The secondary treatment goal was achieved by 72% (21/29) of patients
      treated with isotretinoin, 73% (8/11) of patients treated with acitretin, and 43%
      (6/14) of patients treated with finasteride. Thus, the administration of systemic
      retinoids may be beneficial for the stabilization of frontal hairline in patients
      with FFA. <p><em>J Drugs Dermatol. 2017;16(10):988-992.</em></p>.

PMID- 29036253
TI  - Understanding State Regulation of Biosimilars and Effect on Prescribers.
AB  - Biologics are a mainstay of treatment for many dermatologic conditions, however
      the high costs can be prohibitive for many patients. A growing market of
      biosimilar drugs is emerging with the hope of providing patients access to more
      affordable medications. While the FDA has created an abbreviated licensure
      pathway for these drugs, states are still in the process of creating regulations
      regarding their substitution for reference biologics. This article looks to raise
      awareness of the current federal regulations and the differences among state
      regulations regarding the use of biosimilars. Fifty percent of states have passed
      legislation regarding procedures for substitution of biosimilars in the pharmacy.
      All states require biosimilars to have FDA-approved "interchangeable" status,
      however states vary on other requirements such as: prescriber and patient
      notification, pharmaceutical record keeping, publicly-accessible list of
      interchangeable products, and cost regulations. Some of the issues surrounding
      biosimilar regulation include difficulty obtaining interchangeability status from
      the FDA, resistance to the physician notification requirement, and concern for
      traceability of adverse reactions. Physicians must be aware of current federal
      and state regulations regarding biosimilars and help inform policy makers of the
      potential benefits and shortcoming of biosimilar legislation. <p><em>J Drugs
      Dermatol. 2017;16(10):995-1000.</em></p>.

PMID- 29036254
TI  - Evaluation of Risk of Major Adverse Cardiovascular Events With Biologic Therapy
      in Patients With Psoriasis.
AB  - BACKGROUND: Psoriasis is associated with increased risk of major adverse
      cardiovascular events (MACE). OBJECTIVES: Compare MACE risk with biologics vs
      topical/phototherapy use. METHODS: Psoriasis Longitudinal Assessment Registry
      (PSOLAR) is an international psoriasis registry of patients eligible to receive
      biologic/systemic treatments prospectively. MACE is defined as myocardial
      infarction, stroke, or cardiovascular death. Biologic cohorts, including tumor
      necrosis factor-alpha (TNF-alpha) inhibitors (ie, adalimumab, etanercept, and
      infliximab) and ustekinumab, combined and by class, were compared with a
      topical/phototherapy cohort. Incidence rates of MACE per 100-patient-years
      (100PY) with 95% confidence intervals (95% CI) are reported. Multivariate
      analyses were performed to evaluate the effect of treatment on the risk of MACE
      adjusting for confounders. RESULTS: Analyses included 7550 patients: 6767 in the
      combined biologics cohort (3949 and 2818 in the TNF-alpha inhibitors and
      ustekinumab cohorts, respectively) and 783 in the topical/phototherapy cohort.
      Mean duration of exposure was approximately 2.8 years (combined biologics) and
      4.1 years (topical/phototherapy). A total of 52 MACE were reported; MACE
      incidence rates were 0.22/100PY (95% CI: 0.16, 0.30) for the combined biologics
      cohort (TNF-alpha inhibitors [0.20/100PY (0.12, 0.31)] and ustekinumab
      [0.24/100PY (0.15, 0.37]) and 0.34/100PY (0.17, 0.61) for the
      topical/phototherapy cohort. For the combined biologics (hazard ratio=0.92; 95%
      CI [0.426, 1.988]), TNF-alpha inhibitor (0.85 [0.373, 1.928]), and ustekinumab
      (1.03[0.440, 2.402]) cohorts, treatment was not associated with increased risk of
      MACE versus the topical/phototherapy cohort. CONCLUSION: Based on data
      accumulated to date in PSOLAR, treatment with biologics did not have an impact on
      the risk of MACE in patients with moderate-to-severe psoriasis. <p><em>J Drugs
      Dermatol. 2017;16 (10):1002-1013.</em></p>.

PMID- 29036255
TI  - Tavaborole in Difficult-to-Treat Onychomycosis Cases: A Post-hoc Assessment of
      Phase III Subjects.
AB  - Toenail onychomycosis is a chronic fungal infection that often requires prolonged
      treatment in order to effectively manage pathogenic organisms and obtain a clear
      nail. Traditionally, certain clinical features of onychomycosis, including the
      presence of substantial lateral disease, focal fungal masses, yellow/brown
      streaks, and extensive nail involvement (ie, >50%), indicate a poor treatment
      prognosis and have proven difficult-to-treat with oral or traditional topical
      therapies. Owing to the novel features of topical tavaborole, we sought to
      understand the potential utility of tavaborole in difficult-to-treat
      onychomycosis. A blinded, post-hoc assessment of Phase III trials was conducted,
      focusing on initial presentation, midpoint assessment (24 weeks), and final
      outcomes (52 weeks) in subjects identified as having difficult-to-treat
      onychomycosis and treated for 48 weeks with once-daily application of either
      tavaborole 5% solution or vehicle. Our post-hoc analysis identified 84 difficult
      to-treat cases (tavaborole 5%; n=60; vehicle, n=24) in subjects with toenail
      onychomycosis due to Trichophyton rubrum or Trichophyton mentagrophytes. No
      subjects identified as difficult-to-treat and treated with vehicle achieved a
      complete cure, while 6 subjects treated with tavaborole 5% attained a completely
      clear nail and negative mycology. Similarly, 7 subjects treated with tavaborole
      5% solution achieved an almost complete cure (<=10% involvement and negative
      mycology) while 1 subject on vehicle achieved an almost complete cure. We present
      a case series of 4 patients, of varying age and difficult-to-treat clinical
      features, which responded positively to tavaborole 5% solution. Three of the
      subjects achieved complete cure after being treated with tavaborole 5%, with one
      additional subject (an 88-year-old female) achieving an almost complete clear
      nail by treatment end. The outcomes presented here may not be reflective of
      patients that may present with these clinical characteristics. Additional
      investigations would be useful in order to assess the value of topical tavaborole
      5% solution in difficult-to-treat clinical presentations of onychomycosis.
      <p><em>J Drugs Dermatol. 2017;16(10):1016-1021.</em></p>.

PMID- 29036256
TI  - Pharmacokinetic Comparison of Once-Daily Topical Minocycline Foam 4% vs Oral
      Minocycline for Moderate-to-Severe Acne.
AB  - OBJECTIVE: To characterize minocycline pharmacokinetics and relative
      bioavailability following multiple-dose topical administration of minocycline
      hydrochloride (HCl) foam 4% (FMX101 4%) as compared with single-dose oral
      administration of minocycline HCl extended-release tablets (Solodyn(r)) in
      subjects with moderate-to-severe acne. METHODS: A Phase 1, single-center,
      nonrandomized, open-label, active-controlled, 2-period, 2-treatment crossover
      clinical study. The study included 30 healthy adults (mean age, 22.6 years; 90%
      white, and 60% females) who had moderate-to-severe acne. Subjects were assigned
      to first receive a single oral dose of a minocycline HCl extended-release tablet
      (approximately 1 mg/kg). At 10 days after the oral minocycline dose, topical
      minocycline foam 4% was applied, once daily for 21 days. Serial blood samples
      were obtained before and after administration of oral minocycline and each
      topical application of minocycline foam 4% on days 1, 12, and 21. RESULTS:
      Following oral administration of minocycline (approximately 1 mg/kg), plasma
      minocycline concentration increased until 3 hours, followed by a log-linear
      decrease over the remainder of the 96-hour sampling period. Following topical
      application of a 4-g maximal-use dose of minocycline foam 4% for 21 days, plasma
      minocycline concentration was very low, with geometric mean Cmax values ranging
      from 1.1 ng/mL to 1.5 ng/mL. Steady state was achieved by day 6. Overall,
      minocycline exposure with topical minocycline foam 4% was 730 to 765 times lower
      than that with oral minocycline. There was no evidence of minocycline
      accumulation over the 21 days of topical application of minocycline foam 4%.
      Topical minocycline foam 4% appeared to be safe and well tolerated, with no
      serious treatment-emergent adverse events (TEAEs), treatment-related TEAEs, or
      TEAEs that led to treatment discontinuation. CONCLUSION: Once-daily topical
      application of minocycline foam 4% did not lead to significant systemic exposure
      to minocycline. It appears to be a well-tolerated treatment option for
      individuals with moderate-to-severe acne. <p><em>J Drugs Dermatol.
      2017;16(10):1022-1028.</em></p>.

PMID- 29036257
TI  - Improvement of Actinic Keratoses Using Topical DNA Repair Enzymes: A Randomized
      Placebo-Controlled Trial.
AB  - BACKGROUND: Actinic keratoses (AKs) are proliferations of abnormal keratinocytes,
      which may progress into non-melanoma skin cancers. Although multiple treatment
      modalities exist for AKs, their incidence continues to rise, making new methods
      of both prevention and treatment necessary. DNA repair enzymes have been shown to
      reverse sun-damage, resulting in reduced rates of AKs and non-melanoma skin
      cancer (NMSC) in specific patient populations. OBJECTIVE: We investigated the
      efficacy of a topical DNA repair enzyme lotion as a field therapy for AKs.
      METHODS: In a single center, randomized double-blind study, we randomly assigned
      15 patients with AKs on their face or scalp to receive topical DNA repair enzyme
      lotion or placebo (Eucerin Professional lotion). Lotion was self-applied to a
      treatment field twice daily for 8 consecutive weeks. Complete clearance (primary
      outcome) was assessed at week 8, and local reactions were quantitatively
      measured. Follow-up at week 12 assessed for continued clearance of AKs. RESULTS:
      Thirteen subjects completed the trial. Compared to baseline, patients who used
      the repair enzyme had significantly fewer AKs than those using the control lotion
      after 8-weeks treatment. Specifically, there was a 46.6% percent decrease in AKs
      the DNA repair enzyme lotion group compared to a 32.7% decrease in the placebo
      group. Significance between the two groups was noted at the12 week follow-up,
      where there was an additional 29.2% decrease in AK percentage in the DNA repair
      enzyme group, while the placebo group had a 31.4% increase in AKs (P=0.0026). On
      final self-assessment, 85% of subjects reported being at least "satisfied" with
      the ability of the medication to decrease their AK burden. No side effects were
      reported. CONCLUSION: These results suggest that topical DNA repair enzymes may
      help reduce the number of AKs in individuals with moderate-to-severe photodamaged
      skin. Additionally, there may be a lasting effect of the DNA repair if
      application is discontinued. Further, cutaneous malignancies were not detected in
      any of the subjects during the study period. Despite the brevity of the study,
      these preliminary results suggest the role of DNA repair enzymes for not only
      treatment, but also skin cancer prevention. Further study and more objective
      evaluation measures are required for definitive conclusions to be drawn. <p><em>J
      Drugs Dermatol. 2017;16(10):1030-1034.</em></p>.

PMID- 29036258
TI  - Serpiginous Purpuric Eruption of the Leg.
AB  - A previously healthy 68-year-old male presented with a rash on his right lower
      leg. The lesions had spread along the leg since onset 9 days prior, and the
      patient reported localized soreness and pruritus. He denied systemic symptoms
      including fever, fatigue, myalgia, joint pain, and recent illness. Physical
      examination revealed a serpiginous, purpuric eruption on the anterior and
      posterior right thigh and lower leg. A 4mm punch biopsy from the right lower leg
      revealed a Th2 dominant process reflective of a type IV delayed hypersensitivity
      reaction. Superficial and deep angiocentric and eccrinotropic lymphocytic
      infiltrate and tissue eosinophilia were noted. Degranulated eosinophils forming
      'flame figures' were also identified with accompanying mural edema and red blood
      cell extravasation. Further evaluation revealed an elevated antistreptolysin O
      antibody, though the remainder of the work up was unremarkable.
      Clinicohistopathologic correlation supported the diagnosis of Blaschkolinear
      purpuric Wells' Syndrome. This case highlights a unique presentation of a rare
      inflammatory dermatosis, and serves as a reminder that given Wells' can be
      associated with underlying malignancy, an age appropriate work up, based on
      patient history and presentation, may be warranted. <p><em>J Drugs Dermatol.
      2017;16(10):1036-1038.</em></p>.

PMID- 29036259
TI  - Autoimmune Progesterone Dermatitis: A Diagnosis to Consider in a Patient With
      Cyclical Cutaneous Eruptions.
AB  - Autoimmune progesterone dermatitis (APD) is a cyclical cutaneous reaction to
      progesterone, with symptoms that typically begin 3-10 days before the onset of
      menstrual flow and end 1-2 days into menses. The symptoms vary in severity from
      barely visible to anaphylaxis, but most often include an eczematous eruption,
      erythema multiforme, urticaria, folliculitis, and angioedema. This is a rare
      disorder with only a handful of documented cases. The pathogenesis of this
      condition remains unknown and significant variations in the presentation and
      severity of symptoms complicates its diagnosis. Treatment seeks to inhibit
      progesterone secretion through suppression of ovulation, but it may be
      unsuccessful. We present a case of autoimmune progesterone dermatitis that eluded
      diagnosis for several years, and subsequently the patient was completely
      controlled with oral contraceptive pills. <p><em>J Drugs Dermatol.
      2017;16(10):1040-1042.</em></p>.

PMID- 29036260
TI  - Trimethoprim-Sulfamethoxazole-Induced Drug Eruption With Eosinophilia and
      Systemic Symptoms (DRESS).
AB  - Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe and
      potentially life threatening adverse drug reaction. To help identify DRESS,
      several criteria have been established; however, there is still a lack of
      consensus on diagnosis, and clinical judgment is paramount. Here we describe a 24
      year-old female who presented with a cutaneous eruption, fever, lymphadenopathy,
      eosinophilia, facial edema, and elevated liver enzymes four and a half weeks
      after a 10-day course of Trimethoprim/sulfamethoxazole (TMP/SMX). We used both
      the RegiSCAR and J-SCAR criteria to show the validity of classifying this case as
      DRESS, we also comment on the only other three cases, published to date, that had
      been reported as TMP/SMX induced DRESS. DRESS can be a difficult diagnosis due to
      its diverse symptomatology and delayed presentation - therefore, high suspicion
      and exclusion of other causes is key. Use of validated diagnostic criteria can
      aid the clinician in this regard. In the absence of a well-established therapy,
      early recognition, withdrawal of suspected drug(s), and supportive care play a
      crucial role in the management of DRESS. <p><em>J Drugs Dermatol.
      2017;16(10):1043-1046.</em></p>.

PMID- 29036261
TI  - Development of Halo Nevi in a Lung Cancer Patient: A Novel Immune-Related
      Cutaneous Event from Atezolizumab.
AB  - Immunotherapy-induced vitiligo is an immune-related adverse event (irAE) observed
      in metastatic melanoma patients treated with immune checkpoint inhibitors that
      target the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed
      cell death-1 (PD-1) pathways. To date, the development of leukoderma, poliosis,
      and halo nevi during immunotherapy has largely been reported in metastatic
      melanoma patients. We report a case of immunotherapy-induced leukoderma
      presenting as halo nevi in a patient with non-small cell lung cancer (NSCLC)
      treated with atezolizumab, a programmed cell death ligand (PD-L1) antibody.
      Immunotherapy-induced vitiligo in metastatic melanoma patients may be associated
      with improved survival, but it remains to be determined whether its occurrence in
      non-melanoma cancers has the same prognostic significance. <p><em>J Drugs
      Dermatol. 2017;16(10):1047-1049.</em></p>.

PMID- 29036262
TI  - Granuloma Annulare Secondary to Vemurafenib Therapy for Lung Adenocarcinoma.
AB  - Numerous cutaneous manifestations have been associated with use of BRAF
      inhibitors, including two previously reported cases of granuloma annulare (GA)
      eruptions associated with vemurafenib therapy. Both of these patients were being
      treated for metastatic melanoma. In this report, we describe the case of a 71
      year-old man who developed classic GA lesions while being treated with
      vemurafenib monotherapy for nonmelanoma cancer, specifically metastatic lung
      adenocarcinoma positive for BRAF V600 mutation. <p><em>J Drugs Dermatol.
      2017;16(10):1050-1052.</em></p>.

PMID- 29036263
TI  - Effects of 12C6+ heavy ion beam irradiation on the p53 signaling pathway in HepG2
      liver cancer cells.
AB  - The heavy ion beam is considered to be the ideal source for radiotherapy. The p53
      tumor suppressor gene senses DNA damage and transducts intracellular apoptosis
      signals. Previous reports showed that the heavy ion beam can trigger complex
      forms of damage to cellular DNA, leading to cell cycle arrest and apoptosis of
      HepG2 human liver cancer cells; however, the mechanisms remains unclear fully. In
      order to explore whether the intrinsic or extrinsic pathway participates this
      process, HepG2 cells were treated with 12C6+ HIB irradiation at doses of 0
      (control), 1, 2, 4, and 6 Gy with various methods employed to understand relevant
      mechanisms, such as detection of apoptosis, cell cycle, and Fas expression by
      flow cytometry, analysis of apoptotic morphology by electron microscopy and laser
      scanning confocal microscopy, and screening differentially expressed genes
      relating to p53 signaling pathway by PCR-array assay following with any genes
      confirmed by western blot analysis. This study showed that 12C6+ heavy ion beam
      irradiation at a dose of 6 Gy leads to endogenous DNA double-strand damage, G2/M
      cell cycle arrest, and apoptosis of human HepG2 cells via synergistic effect of
      the extrinsic and intrinsic pathways. Differentially expressed genes in the p53
      signaling pathway related to DNA damage repair, apoptosis, cycle regulation,
      metastasis, deterioration and radioresistance were also discovered. Consequently,
      the expressions of Fas, TP53BP2, TP53AIP1, and CASP9 were confirmed upregulated
      after 12C6+ HIB irradiation treatment. In conclusion, this study demonstrated the
      mechanisms of inhibition and apoptosis induced by 12C6+ heavy ion beam
      irradiation on HepG2 cancer cells is mediated by initiation of the biological
      function of p53 signaling pathway including extrinsic and intrinsic apoptosis
      pathway.

PMID- 29036264
TI  - Immature colon carcinoma transcript-1 promotes proliferation of gastric cancer
      cells.
AB  - Gastric cancer is the fourth most common malignant tumor and has been considered
      as one of the leading causes of cancer-related death worldwide. The
      identification of the molecular mechanism during gastric cancer progression is
      urgently needed, which will help to develop more effective treatment strategies.
      As a component of the human mitoribosome, immature colon carcinoma transcript-1
      (ICT1) might be involved in tumor formation and progression. However, its
      biological function and the corresponding mechanism in gastric cancer have been
      poorly characterized. To study the mechanism of ICT1 in gastric cancer, we first
      investigated the mRNA levels of ICT1 in human normal and gastric cancer tissues
      using datasets from the publicly available Oncomine database. The results showed
      that ICT1 is overexpressed in gastric cancer tissues. Then in order to study the
      role of ICT1 in gastric cancer, two shRNAs were used to silence ICT1 in MGC80-3
      and AGS cells. Functional analysis showed ICT1 knockdown significantly inhibited
      the proliferation of gastric cancer cells and induced apoptosis. Further,
      mechanistic study demonstrated that ICT1 silencing induced cell-cycle arrest at
      G2/M phase via the suppression of cyclin A2 and cyclin B1. In addition, ICT1
      silencing also increased cleaved caspase-3 and activated PARP in gastric cancer
      cells. These findings suggest that ICT1 may play a crucial role in promoting
      gastric cancer proliferation in vitro.

PMID- 29036265
TI  - Short-Term Blood Pressure Variability and Cognition in the Elderly: Mere
      Association or a Key Mechanism?

PMID- 29036266
TI  - Alterations in NO/ROS ratio and expression of Trx1 and Prdx2 in isoproterenol
      induced cardiac hypertrophy.
AB  - The development of cardiac hypertrophy is a complicated process, which undergoes
      a transition from compensatory hypertrophy to heart failure, and the
      identification of new biomarkers and targets for this disease is greatly needed.
      Here we investigated the development of isoproterenol (ISO)-induced cardiac
      hypertrophy in an in vitro experimental model. After the induction of hypertrophy
      with ISO treatment in H9c2 cells, cell surface area, cell viability, cellular
      reactive oxygen species (ROS), and nitric oxide (NO) levels were tested. Our data
      showed that the cell viability, mitochondrial membrane potential, and NO/ROS
      balance varied during the development of cardiac hypertrophy in H9c2 cells. It
      was also found that the expression of thioredoxin1 (Trx1) and peroxiredoxin2
      (Prdx2) was decreased during the cardiac hypertrophy of H9c2 cells. These results
      suggest a critical role for Trx1 and Prdx2 in the cardiac hypertrophy of H9c2
      cells and in the transition from compensated hypertrophy to de-compensated
      hypertrophy in H9c2 cells, and our findings may have important implications for
      the management of this disease.

PMID- 29036267
TI  - Electrical Activity of the Heart Under Pressure.

PMID- 29036268
TI  - Breast Cancer Estrogen Receptor Status According to Biological Generation: US
      Black and White Women Born 1915-1979.
AB  - Evidence suggests that contemporary population distributions of estrogen-receptor
      (ER) status among breast cancer patients may be shaped by earlier major societal
      events, such as the 1965 abolition of legal racial discrimination in the United
      States (state and local "Jim Crow" laws) and the Great Famine in China (1959
      1961). We analyzed changes in ER status in relation to Jim Crow birthplace among
      the 46,417 black and 339,830 white US-born, non-Hispanic women in the
      Surveillance, Epidemiology, and End Results (SEER) 13 Registry Group who were
      born between 1915 and 1979 and diagnosed (ages 25-84 years, inclusive) during
      1992-2012. We grouped the cases according to birth cohort and quantified the rate
      of change using the haldane (which scales change in relation to biological
      generation). The percentage of ER-positive cases rose according to birth cohort
      (1915-1919 to 1975-1979) only among women diagnosed before age 55. Changes
      according to biological generation were greater among black women than among
      white women, and among black women, they were greatest among those born in Jim
      Crow (versus non-Jim Crow) states, with this group being the only group to
      exhibit high haldane values (>|0.3|, indicating high rate of change). Our study's
      analytical approach and findings underscore the need to consider history and
      societal context when analyzing ER status among breast cancer patients and
      racial/ethnic inequities in its distribution.

PMID- 29036270
TI  - On expert curation and scalability: UniProtKB/Swiss-Prot as a case study.
AB  - Motivation: Biological knowledgebases, such as UniProtKB/Swiss-Prot, constitute
      an essential component of daily scientific research by offering distilled,
      summarized and computable knowledge extracted from the literature by expert
      curators. While knowledgebases play an increasingly important role in the
      scientific community, their ability to keep up with the growth of biomedical
      literature is under scrutiny. Using UniProtKB/Swiss-Prot as a case study, we
      address this concern via multiple literature triage approaches. Results: With the
      assistance of the PubTator text-mining tool, we tagged more than 10 000 articles
      to assess the ratio of papers relevant for curation. We first show that curators
      read and evaluate many more papers than they curate, and that measuring the
      number of curated publications is insufficient to provide a complete picture as
      demonstrated by the fact that 8000-10 000 papers are curated in UniProt each year
      while curators evaluate 50 000-70 000 papers per year. We show that 90% of the
      papers in PubMed are out of the scope of UniProt, that a maximum of 2-3% of the
      papers indexed in PubMed each year are relevant for UniProt curation, and that,
      despite appearances, expert curation in UniProt is scalable. Availability and
      implementation: UniProt is freely available at http://www.uniprot.org/. Contact:
      sylvain.poux@sib.swiss. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29036269
TI  - Longitudinal Blood Pressure Changes and Kidney Function Decline in Persons
      Without Chronic Kidney Disease: Findings From the MESA Study.
AB  - BACKGROUND: While changes in blood pressure (BP) are independently associated
      with cardiovascular events, less is known about the association between changes
      in BP and subsequent changes in renal function in adults with an estimated
      glomerular filtration rate (eGFR) of >60 ml/min/1.73 m2. METHODS: The present
      study included 3,920 participants in the Multi-Ethnic Study of Atherosclerosis
      (MESA) study who had >=2 BP measurements during the first 5 years of MESA and had
      eGFR measurements at both year 5 and 10. Change in BP was estimated as the
      annualized slope of BP between year 0 and 5 based on linear mixed models (mean
      number of measurements = 4.0). Participants were then grouped into 1 of 3
      categories based on the distribution of systolic BP (SBP), diastolic BP (DBP),
      and pulse pressure (PP) change (top 20%, middle 21-79%, bottom 20%). We
      calculated eGFR from cystatin C (ml/min/1.73 m2), estimated annual change in eGFR
      (ml/min/1.73 m2/year), and defined rapid kidney function decline as a >30%
      decrease in eGFR from year 5 to 10. We used multivariable logistic regression
      adjusting for year 0 demographic and clinical characteristics, including eGFR and
      BP, to determine associations of BP change with rapid kidney function decline.
      RESULTS: Median age was 59 [interquartile range (IQR): 52, 67] and median eGFR at
      year 0 was 95.5 (IQR: 81.7, 105.9) ml/min/1.73 m2. Median SBP at year 0 was 111,
      121, and 147 mm Hg for increasing, stable, and decreasing SBP change,
      respectively. Increasing SBP and widening PP change were each associated with
      higher odds of rapid kidney function decline compared with stable SBP and PP
      groups, respectively [odds ratio, OR 1.7 (95% confidence interval, CI 1.3, 2.4)
      for SBP; OR 1.4 (95% CI 1.1, 1.9) for PP]. Decreasing SBP was associated with
      rapid kidney function decline after adjusting for all covariates except for year
      0 BP [OR 1.4 (95% CI 1.0, 1.8)], but this association was no longer statistically
      significant after adjustment for year 0 BP. There were no significant
      associations between DBP change and rapid decline in the fully adjusted models.
      Similar findings were seen with annual change in eGFR. CONCLUSIONS: Increasing
      SBP and widening PP over time were associated with greater risk for accelerated
      kidney function decline even at BP levels below established hypertension
      thresholds.

PMID- 29036271
TI  - Cancer Hallmarks Analytics Tool (CHAT): a text mining approach to organize and
      evaluate scientific literature on cancer.
AB  - Motivation: To understand the molecular mechanisms involved in cancer
      development, significant efforts are being invested in cancer research. This has
      resulted in millions of scientific articles. An efficient and thorough review of
      the existing literature is crucially important to drive new research. This time
      demanding task can be supported by emerging computational approaches based on
      text mining which offer a great opportunity to organize and retrieve the desired
      information efficiently from sizable databases. One way to organize existing
      knowledge on cancer is to utilize the widely accepted framework of the Hallmarks
      of Cancer. These hallmarks refer to the alterations in cell behaviour that
      characterize the cancer cell. Results: We created an extensive Hallmarks of
      Cancer taxonomy and developed automatic text mining methodology and a tool (CHAT)
      capable of retrieving and organizing millions of cancer-related references from
      PubMed into the taxonomy. The efficiency and accuracy of the tool was evaluated
      intrinsically as well as extrinsically by case studies. The correlations
      identified by the tool show that it offers a great potential to organize and
      correctly classify cancer-related literature. Furthermore, the tool can be
      useful, for example, in identifying hallmarks associated with extrinsic factors,
      biomarkers and therapeutics targets. Availability and implementation: CHAT can be
      accessed at: http://chat.lionproject.net. The corpus of hallmark-annotated PubMed
      abstracts and the software are available at: http://chat.lionproject.net/about.
      Contact: simon.baker@cl.cam.ac.uk. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 29036272
TI  - Lep-MAP3: robust linkage mapping even for low-coverage whole genome sequencing
      data.
AB  - Motivation: Accurate and dense linkage maps are useful in family-based linkage
      and association studies, quantitative trait locus mapping, analysis of genome
      synteny and other genomic data analyses. Moreover, linkage mapping is one of the
      best ways to detect errors in de novo genome assemblies, as well as to orient and
      place assembly contigs within chromosomes. A small mapping cross of tens of
      individuals will detect many errors where distant parts of the genome are
      erroneously joined together. With more individuals and markers, even more local
      errors can be detected and more contigs can be oriented. However, the tools that
      are currently available for constructing linkage maps are not well suited for
      large, possible low-coverage, whole genome sequencing datasets. Results: Here we
      present a linkage mapping software Lep-MAP3, capable of mapping high-throughput
      whole genome sequencing datasets. Such data allows cost-efficient genotyping of
      millions of single nucleotide polymorphisms (SNPs) for thousands of individual
      samples, enabling, among other analyses, comprehensive validation and refinement
      of de novo genome assemblies. The algorithms of Lep-MAP3 can analyse low-coverage
      datasets and reduce data filtering and curation on any data. This yields more
      markers in the final maps with less manual work even on problematic datasets. We
      demonstrate that Lep-MAP3 obtains very good performance already on 5x sequencing
      coverage and outperforms the fastest available software on simulated data on
      accuracy and often on speed. We also construct de novo linkage maps on 7-12x
      whole-genome data on the Red postman butterfly (Heliconius erato) with almost 3
      million markers. Availability and implementation: Lep-MAP3 is available with the
      source code under GNU general public license from
      http://sourceforge.net/projects/lep-map3. Contact: pasi.rastas@helsinki.fi.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29036273
TI  - SCooP: an accurate and fast predictor of protein stability curves as a function
      of temperature.
AB  - Motivation: The molecular bases of protein stability remain far from elucidated
      even though substantial progress has been made through both computational and
      experimental investigations. One of the most challenging goals is the development
      of accurate prediction tools of the temperature dependence of the standard
      folding free energy DeltaG(T). Such predictors have an enormous series of
      potential applications, which range from drug design in the biopharmaceutical
      sector to the optimization of enzyme activity for biofuel production. There is
      thus an important demand for novel, reliable and fast predictors. Results: We
      present the SCooP algorithm, which is a significant step towards accurate
      temperature-dependent stability prediction. This automated tool uses the protein
      structure and the host organism as sole entries and predicts the full T-dependent
      stability curve of monomeric proteins assumed to follow a two-state folding
      transition. Equivalently, it predicts all the thermodynamic quantities associated
      to the folding transition, namely the melting temperature Tm, the standard
      folding enthalpy DeltaHm measured at Tm, and the standard folding heat capacity
      DeltaCp. The cross-validated performances are good, with correlation coefficients
      between predicted and experimental values equal to [0.80, 0.83, 0.72] for
      DeltaHm, DeltaCp and Tm, respectively, which increase up to [0.88, 0.90, 0.78]
      upon the removal of 10% outliers. Moreover, the stability curve prediction of a
      target protein is very fast: it takes less than a minute. SCooP can thus
      potentially be applied on a structurome scale. This opens new perspectives of
      large-scale analyses of protein stability, which is of considerable interest for
      protein engineering. Availability and implementation: The SCooP webserver is
      freely available at http://babylone.ulb.ac.be/SCooP. Contact: fapucci@ulb.ac.be,
      jkwasigr@ulb.ac.be or mrooman@ulb.ac.be. Supplementary information: Supplementary
      data are available at Bioinformatics online.

PMID- 29036274
TI  - A robust DF-REML framework for variance components estimation in genetic studies.
AB  - Motivation: In genetic association studies, linear mixed models (LMMs) are used
      to test for associations between phenotypes and candidate single nucleotide
      polymorphisms (SNPs). These same models are also used to estimate heritability,
      which is central not only to evolutionary biology but also to the prediction of
      the response to selection in plant and animal breeding, as well as the prediction
      of disease risk in humans. However, when one or more of the underlying
      assumptions are violated, the estimation of variance components may be
      compromised and therefore so may the estimates of heritability and any other
      functions of these. Considering that datasets obtained from real life experiments
      are prone to several sources of contamination, which usually induce the violation
      of the assumption of the normality of the errors, a robust derivative-free
      restricted-maximum likelihood framework (DF-REML) together with a robust
      coefficient of determination are proposed for the LMM in the context of genetic
      studies of continuous traits. Results: The proposed approach, in addition to the
      robust estimation of variance components and robust computation of the
      coefficient of determination, allows in particular for the robust estimation of
      SNP-based heritability by reducing the bias and increasing the precision of its
      estimates. The performance of both classical and robust DF-REML approaches is
      compared via a Monte Carlo simulation study. Additionally, three examples of
      application of the methodologies to real datasets are given in order to validate
      the usefulness of the proposed robust approach. Although the main focus of this
      article is on plant breeding applications, the proposed methodology is applicable
      to both human and animal genetic studies. Availability and implementation: Source
      code implemented in R is available in the Supplementary Material. Contact:
      vmml@fct.unl.pt. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 29036275
TI  - Porcupine-dependent Wnt activity within the uterine epithelium is essential for
      fertility.
AB  - The secretion of mammalian Wnt ligands within the cell is dependent on the
      activity of Porcupine, a gene located on the X-chromosome that encodes for a
      membrane-bound O-acyl transferase. Here, we report that postnatal ablation of
      Porcupine in the uterine luminal epithelium alone results in the decrease in
      endometrial gland number. Despite having uterine glands, mutant females are
      completely infertile. Epithelial ablation of Porcupine causes defects in timely
      apposition of the lumen, along with failure to respond to artificial decidual
      induction. Interestingly, progesterone supplementation was able to rescue the
      initiation of decidualization, but the decidua was not maintained and
      subsequently resorbed. Transcriptome analysis demonstrated that deletion of
      Porcupine in the epithelium resulted in the stromal dysregulation of members of
      the Wnt signaling pathway (Lef1, Wnt4, and Wnt16), dysregulation of receptors and
      ligands in the Notch signaling pathway (Notch1, Notch4, and Dll4) as well as
      Hoxa10. Our results demonstrate the crucial requirement of Wnt signaling in the
      epithelium for fertility and demonstrate that epithelial Wnts regulate stromal
      Wnt gene expression as well as regulating the expression of essential signaling
      factors and effectors required for successful embryo implantation.

PMID- 29036277
TI  - PySeqLab: an open source Python package for sequence labeling and segmentation.
AB  - Motivation: Text and genomic data are composed of sequential tokens, such as
      words and nucleotides that give rise to higher order syntactic constructs. In
      this work, we aim at providing a comprehensive Python library implementing
      conditional random fields (CRFs), a class of probabilistic graphical models, for
      robust prediction of these constructs from sequential data. Results: Python
      Sequence Labeling (PySeqLab) is an open source package for performing supervised
      learning in structured prediction tasks. It implements CRFs models, that is
      discriminative models from (i) first-order to higher-order linear-chain CRFs, and
      from (ii) first-order to higher-order semi-Markov CRFs (semi-CRFs). Moreover, it
      provides multiple learning algorithms for estimating model parameters such as (i)
      stochastic gradient descent (SGD) and its multiple variations, (ii) structured
      perceptron with multiple averaging schemes supporting exact and inexact search
      using 'violation-fixing' framework, (iii) search-based probabilistic online
      learning algorithm (SAPO) and (iv) an interface for Broyden-Fletcher-Goldfarb
      Shanno (BFGS) and the limited-memory BFGS algorithms. Viterbi and Viterbi A* are
      used for inference and decoding of sequences. Using PySeqLab, we built models
      (classifiers) and evaluated their performance in three different domains: (i)
      biomedical Natural language processing (NLP), (ii) predictive DNA sequence
      analysis and (iii) Human activity recognition (HAR). State-of-the-art performance
      comparable to machine-learning based systems was achieved in the three domains
      without feature engineering or the use of knowledge sources. Availability and
      implementation: PySeqLab is available through https://bitbucket.org/A_2/pyseqlab
      with tutorials and documentation. Contact: ahmed.allam@yale.edu or
      michael.krauthammer@yale.edu. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29036276
TI  - Multimorbidity: will it stand the test of time?
AB  - The concept of multimorbidity has risen in popularity over the past few years.
      Its use has led to, or coincided with, an increased recognition that patients
      often have more than one health problem which should not be treated in isolation.
      The motivation for more holistic, person-centred care that lies behind
      multimorbidity is to be welcomed. The 2016 National Institute for Health and Care
      Excellence multimorbidity management guideline helpfully makes recommendations in
      key areas that are important in the care of patients with complicated medical
      problems.However, we question the sustainability of the term for the following
      four reasons: (i) it is doctor and researcher centred rather than patient
      centred, focusing upon the number of diagnoses rather than the patient's lived
      experience, (ii) it is not a positive term for patients and is at odds with the
      move towards promoting active and healthy ageing, (iii) its non-specific nature
      means it holds little value in daily clinical practice and (iv) most definitions
      apply to a large segment of the population making it of limited use for health
      care planners. We argue that the complementary concepts of complexity and frailty
      would fit better with the delivery of patient centred care for people with
      multiple co-existing health problems and would be more useful to clinicians,
      commissioners and researchers.

PMID- 29036278
TI  - Perceptions of risk and therapy among patients with Barrett's esophagus: a
      patient survey study.
AB  - Nondysplastic Barrett's esophagus has a risk of progression to esophageal
      adenocarcinoma as low as 0.18-0.3% per person per year, and low-grade dysplasia
      as low as 0.5%. While adherence to guidelines and selection of management options
      varies, little is known about what modifies patient decision-making. This study
      aims to evaluate and identify factors that influence patient perceptions of risk
      and decisions about management. An independently developed and piloted survey was
      administered to patients at an academic hospital. Risk perception and desire for
      therapy were assessed using a standard reference gamble paradigm, and responses
      were stratified based on patient and disease characteristics. Data were analyzed
      with Student's t and chi-squared tests. A total of 42 of 50 patients with
      Barrett's esophagus and no prior endoscopic therapy participated (84% response;
      76% nondysplastic Barrett's esophagus, 22% low-grade dysplasia, 2% indeterminate
      for dysplasia; mean age 61 years, 29% female). On average, patients perceived
      their risk of developing esophageal adenocarcinoma in the next year, 10 years and
      lifetime as 6, 14, and 19%, respectively. Nearly half viewed their lifetime risk
      of developing esophageal adenocarcinoma to be the same or higher than diabetes,
      heart disease, or colon cancer. Although 92% of patients felt surveillance
      beneficial, only 54% believed endoscopic therapy to be effective in most or all
      cases. As many as 83% of patients were willing to undergo endoscopic therapy with
      a hypothetical success rate as low as 70%, and a majority (64%) accepted
      complication rates up to 30%. Compared to patients with low risk perception of
      developing esophageal adenocarcinoma, those with high risk perception more often
      believed their risk for developing esophageal adenocarcinoma was greater than
      diabetes (p = 0.04) or colon cancer (p = 0.002). Those with lifetime low risk
      perception were less likely to accept modest complication rates (<10%) of therapy
      (P < 0.05). Age, gender, degree of dysplasia, lifetime endoscopies and duration
      of symptoms had no impact on perceived effectiveness of surveillance or therapy,
      and did not correlate with desire for treatment at varying levels of risk and
      effectiveness. Patients with Barrett's esophagus overestimate their risk of
      developing esophageal adenocarcinoma and will accept low success rates and high
      risk of complications to undergo endoscopic therapy. Baseline risk perception
      correlates with the desire for endoscopic therapy.

PMID- 29036279
TI  - Strong inhibition of neutrophil-sperm interaction in cattle by selective
      phosphatidylinositol 3-kinase inhibitors.
AB  - The vast majority of sperm are lost from the female reproductive tract in hours
      following natural mating or artificial insemination in mammals. Multiple complex
      processes including uterine contractions, mucus barriers, and phagocytosis of
      sperm by neutrophils have been reported to be involved in the sperm loss,
      although the contribution of each process is uncertain. If phagocytosis by
      neutrophils has a significant role in sperm loss, inhibition of neutrophil
      response to sperm could potentially reduce the dose of sperm required for
      artificial insemination. Through the development of a quantitative in vitro
      assay, we have screened 74 candidate compounds for their ability to inhibit the
      neutrophil-sperm interaction in cattle. Nine inhibitors (GSK2126458, wortmannin,
      ZSTK474, PIK294, CAL-101, GSK 1059615, GDC-0941, PIK 90 and PI103) active against
      phosphatidylinositol 3-kinase (PI3-kinase) were most potent, and strongly reduced
      neutrophil-sperm interaction with an IC50 of 10 nM or less. These inhibitors did
      not significantly modify sperm motility, and five of the inhibitors did not
      affect in vitro fertilization. Examination of neutrophil-sperm interaction by
      time-lapse video microscopy and cell tracking analysis revealed that GSK2126458
      may prevent sperm phagocytosis through inhibition of neutrophil movement and/or
      attachment. Twenty-four other compounds exhibited weaker inhibition (IC50 < 115
      MUM), and the rest did not inhibit the neutrophil-sperm interaction. Strong PI3
      kinase inhibitors identified in this study may be useful to determine the
      contribution of neutrophil phagocytosis in the clearance of sperm from the female
      reproductive tract.

PMID- 29036280
TI  - Invited Commentary: Sex and Race Differences in Diabetes and Cardiovascular
      Disease-Achieving the Promise of Sex and Race Subgroup Analyses in Epidemiologic
      Research.
AB  - Diabetes confers a higher risk of cardiovascular disease on women than on men.
      The reasons for these sex differences, such as poorer cardiovascular risk factor
      profiles, have received considerable attention. However, a recent report on sex *
      diabetes interactions on cardiovascular disease identified that few if any prior
      studies have confirmed these sex differences in black individuals, despite known
      diabetes-related disparities. In this issue of the Journal, George et al. (Am J
      Epidemiol. 2018;187(3):403-410.) found marginally significant multiplicative sex
      * diabetes interactions in black but not white study participants after
      adjustments for traditional and behavioral risk factors, competing risk, and
      change in diabetes status over time. This study is notable for its attempt to
      fill an important literature gap, and it elegantly addressed multiple statistical
      considerations in assessing sex * diabetes interactions according to race strata.
      The findings also highlighted several important considerations for conducting
      race and sex subgroup analyses.

PMID- 29036281
TI  - Changing paradigms in oral anticoagulation during cardioversion in Europe.

PMID- 29036282
TI  - THE AUTHORS REPLY.

PMID- 29036283
TI  - The Science of Absent Evidence: Is There Such Thing as an Effective Responsible
      Drinking Message?
AB  - Aims: To review the effectiveness of responsible drinking messages (RDMs).
      Methods: We searched PsycINFO, MEDLINE and Google Scholar to June 2016 for
      studies evaluating the effectiveness of RDMs. Only eight studies met the
      inclusion/exclusion criteria. Due to a small number of search results and broad
      inconsistency in methods and outcome measures, quantitative synthesis was not
      possible so a narrative summary of findings was conducted. Results: A review of
      findings from these articles suggested a disjointed approach in terms of the
      format and content of RDMs evaluated, as well as the dependent variables used to
      judge their effectiveness. An overall pattern emerged suggesting that RDMs may
      have beneficial effects across various outcome measures, including reducing
      prospective alcohol use. However, due to the inconsistent approach to both the
      development and evaluation of RDMs, it was not possible to draw any clear
      conclusions in terms of effectiveness, or indeed the potential size of any
      effects. Conclusions: A systematic approach to the development and evaluation of
      RDMs is recommended to ensure that a clearer evidence base is established in this
      area, particularly in light of the substantial public funds which are often spent
      on RDM campaigns. Short summary: A systematic review of studies evaluating the
      effectiveness of responsible drinking message campaigns reveals an inconsistent
      approach to message design and evaluation. Findings of the review suggest the
      need for a more consistent approach to aid in the development of a clearer
      evidence base in this area.

PMID- 29036285
TI  - Relevance of low miR-30c-5p levels in atherogenesis: a promising predictive
      biomarker and potential therapeutic target.

PMID- 29036284
TI  - Airway volume analysis: is there a correlation between two and three-dimensions?
AB  - Objectives: No consensus exists on the assessment of airway in CBCT scans. Two
      dimensional measures remain the standard in the cephalometric analysis. This
      research aimed to evaluate linear and area measurements in two-dimensional views
      from specific airway regions of interest and compare these to the correspondent
      volume in CBCT exams. Materials and Methods: 250-selected CBCT scans were
      retrospectively analyzed. A trained and calibrated examiner performed the linear,
      area and volume measurements in specific sites for nasal cavity, nasopharynx and
      oropharynx compartments. Dolphin Software was used for the analysis. The
      correlations were performed using Pearson coefficient. Results: The highest
      positive correlations were observed in the nasopharynx and oropharynx sagittal
      areas and the most constricted area in the oropharynx. Nasopharynx linear
      measures and nasopharynx coronal area did not present correlation with whole
      volume. Two-dimensional measurements in the soft palate (width and sagittal area)
      showed very low positive correlations. Although nasal cavity presented highest
      volume means, changes in oropharynx contributed more to variations in total
      volume, compared with the other two sections. Conclusion: Airway sagittal areas,
      as well as the most constricted axial area in oropharynx remains a useful guide
      to correlate with airway volume in two-dimensional images.

PMID- 29036286
TI  - Participation rates by educational levels have diverged during 25 years in
      Finnish health examination surveys.
AB  - Background: Declining participation rates in health examination surveys may
      impair the representativeness of surveys and introduce bias into the comparison
      of results between population groups if participation rates differ between them.
      Changes in the characteristics of non-participants over time may also limit
      comparability with earlier surveys. Methods: We studied the association of socio
      economic position with participation, and its changes over the past 25 years.
      Occupational class and educational level are used as indicators of socio-economic
      position. Data from six cross-sectional FINRISK surveys conducted between 1987
      and 2012 in Finland were linked to national administrative registers, which
      allowed investigation of the differences between survey participants and non
      participants. Results: Our results show that individuals with low occupational
      class or low level of education were less likely to participate than individuals
      with high occupational class or high level of education. Participation rates
      decreased in all subgroups of the population but the decline was fastest among
      those with low level of education. Conclusions: The differences in participation
      rates must be taken into account to avoid biased estimates because socio-economic
      position has also been shown to be strongly related to health, health behaviour
      and biological risk factors. Particular attention should be paid to the
      recruitment of the less-educated population groups.

PMID- 29036287
TI  - powsimR: power analysis for bulk and single cell RNA-seq experiments.
AB  - Summary: Power analysis is essential to optimize the design of RNA-seq
      experiments and to assess and compare the power to detect differentially
      expressed genes in RNA-seq data. PowsimR is a flexible tool to simulate and
      evaluate differential expression from bulk and especially single-cell RNA-seq
      data making it suitable for a priori and posterior power analyses. Availability
      and implementation: The R package and associated tutorial are freely available at
      https://github.com/bvieth/powsimR. Contact: vieth@bio.lmu.de or
      hellmann@bio.lmu.de. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29036288
TI  - Strategies for Partitioning Clock Models in Phylogenomic Dating: Application to
      the Angiosperm Evolutionary Timescale.
AB  - Evolutionary timescales can be inferred from molecular sequence data using a
      Bayesian phylogenetic approach. In these methods, the molecular clock is often
      calibrated using fossil data. The uncertainty in these fossil calibrations is
      important because it determines the limiting posterior distribution for
      divergence-time estimates as the sequence length tends to infinity. Here, we
      investigate how the accuracy and precision of Bayesian divergence-time estimates
      improve with the increased clock-partitioning of genome-scale data into clock
      subsets. We focus on a data set comprising plastome-scale sequences of 52
      angiosperm taxa. There was little difference among the Bayesian date estimates
      whether we chose clock-subsets based on patterns of among-lineage rate
      heterogeneity or relative rates across genes, or by random assignment. Increasing
      the degree of clock-partitioning usually led to an improvement in the precision
      of divergence-time estimates, but this increase was asymptotic to a limit
      presumably imposed by fossil calibrations. Our clock-partitioning approaches
      yielded highly precise age estimates for several key nodes in the angiosperm
      phylogeny. For example, when partitioning the data into 20 clock-subsets based on
      patterns of among-lineage rate heterogeneity, we inferred crown angiosperms to
      have arisen 198-178 Ma. This demonstrates that judicious clock-partitioning can
      improve the precision of molecular dating based on phylogenomic data, but the
      meaning of this increased precision should be considered critically.

PMID- 29036289
TI  - VICTOR: genome-based phylogeny and classification of prokaryotic viruses.
AB  - Motivation: Bacterial and archaeal viruses are crucial for global biogeochemical
      cycles and might well be game-changing therapeutic agents in the fight against
      multi-resistant pathogens. Nevertheless, it is still unclear how to best use
      genome sequence data for a fast, universal and accurate taxonomic classification
      of such viruses. Results: We here present a novel in silico framework for
      phylogeny and classification of prokaryotic viruses, in line with the principles
      of phylogenetic systematics, and using a large reference dataset of officially
      classified viruses. The resulting trees revealed a high agreement with the
      classification. Except for low resolution at the family level, the majority of
      taxa was well supported as monophyletic. Clusters obtained with distance
      thresholds chosen for maximizing taxonomic agreement appeared phylogenetically
      reasonable, too. Analysis of an expanded dataset, containing >4000 genomes from
      public databases, revealed a large number of novel species, genera, subfamilies
      and families. Availability and implementation: The selected methods are available
      as the easy-to-use web service 'VICTOR' at https://victor.dsmz.de. Contact:
      jan.meier-kolthoff@dsmz.de. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29036292
TI  - Association between implantable cardioverter-defibrillator therapy and different
      lead positions in patients with cardiac resynchronization therapy.
AB  - Aims: To evaluate the impact of different right and left ventricular lead
      positions (RV-LP and LV-LP) on the risk of therapy for ventricular
      tachycardia/ventricular fibrillation in patients with a cardiac resynchronization
      therapy device (CRT-D). Methods and results: We performed a large nationwide
      cohort study on patients in Denmark receiving a CRT-D device from 2008 to 2012
      from the Danish Pacemaker and implantable cardioverter defibrillator (ICD)
      registry. Lead positions were registered during the implantation and categorized
      as anterior/lateral/posterior and basal/mid-ventricular/apical for the LV-LP, and
      as apical/non-apical for the RV-LP. Appropriate and inappropriate therapies were
      registered during follow-up via remote monitoring or at device interrogations.
      Time to event was summarized with Kaplan-Meier plots, and competed risk
      regression analysis was used to calculate adjusted hazard ratios (aHR) with 95%
      confidence intervals (CI). Following variables were included in the analysis:
      gender, age, heart failure aetiology, New York heart association class, left
      ventricular ejection fraction, QRS duration, indication (secondary or primary
      prophylactic), RV-LP, LV-LP, and antiarrhythmic therapy. We included 1643
      patients [mean age 68 (+/-10) years, 1343 (83%) men]. After a mean of 2.0 years,
      322 (20%) patients received appropriate and 66 (4%) patients received
      inappropriate therapy. The aHR for appropriate therapy with a non-apical RV-LP
      was 0.70 95% CI (0.55-0.87, P = 0.002) as compared with an apical. We observed no
      significant association between appropriate therapy and LV-LP in left anterior
      oblique or right anterior oblique views or inappropriate therapy between any lead
      positions. Conclusion: An apical RV-LP is associated with an increased risk of
      appropriate therapy for ventricular tachyarrhythmia in patients with a CRT-D
      device.

PMID- 29036291
TI  - Phylotyper: in silico predictor of gene subtypes.
AB  - Summary: Whole genome sequencing (WGS) is being adopted in public health for
      improved surveillance and outbreak analysis. In public health, subtyping has been
      used to infer phenotypes and distinguish bacterial strain groups. In silico tools
      that predict subtypes from sequences data are needed to transition historical
      data to WGS-based protocols. Phylotyper is a novel solution for in silico subtype
      prediction from gene sequences. Designed for incorporation into WGS pipelines, it
      is a general prediction tool that can be applied to different subtype schemes.
      Phylotyper uses phylogeny to model the evolution of the subtype and infer
      subtypes for unannotated sequences. The phylogenic framework in Phylotyper
      improves accuracy over approaches based solely on sequence similarity and
      provides useful contextual feedback. Availability and implementation: Phylotyper
      is a python and R package. It is available from:
      https://github.com/superphy/insilico-subtyping. Contact: matthew.whiteside@phac
      aspc.gc.ca. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 29036290
TI  - Comparative Genomics of Apomictic Root-Knot Nematodes: Hybridization, Ploidy, and
      Dynamic Genome Change.
AB  - The root-knot nematodes (genus Meloidogyne) are important plant parasites causing
      substantial agricultural losses. The Meloidogyne incognita group (MIG) of
      species, most of which are obligatory apomicts (mitotic parthenogens), are
      extremely polyphagous and important problems for global agriculture. While
      understanding the genomic basis for their variable success on different crops
      could benefit future agriculture, analyses of their genomes are challenging due
      to complex evolutionary histories that may incorporate hybridization, ploidy
      changes, and chromosomal fragmentation. Here, we sequence 19 genomes,
      representing five species of key root-knot nematodes collected from different
      geographic origins. We show that a hybrid origin that predated speciation within
      the MIG has resulted in each species possessing two divergent genomic copies.
      Additionally, the apomictic MIG species are hypotriploids, with a proportion of
      one genome present in a second copy. The hypotriploid proportion varies among
      species. The evolutionary history of the MIG genomes is revealed to be very
      dynamic, with noncrossover recombination both homogenizing the genomic copies,
      and acting as a mechanism for generating divergence between species.
      Interestingly, the automictic MIG species M. floridensis differs from the apomict
      species in that it has become homozygous throughout much of its genome.

PMID- 29036294
TI  - RealityConvert: a tool for preparing 3D models of biochemical structures for
      augmented and virtual reality.
AB  - Motivation: There is a growing interest for the broad use of Augmented Reality
      (AR) and Virtual Reality (VR) in the fields of bioinformatics and cheminformatics
      to visualize complex biological and chemical structures. AR and VR technologies
      allow for stunning and immersive experiences, offering untapped opportunities for
      both research and education purposes. However, preparing 3D models ready to use
      for AR and VR is time-consuming and requires a technical expertise that severely
      limits the development of new contents of potential interest for structural
      biologists, medicinal chemists, molecular modellers and teachers. Results: Herein
      we present the RealityConvert software tool and associated website, which allow
      users to easily convert molecular objects to high quality 3D models directly
      compatible for AR and VR applications. For chemical structures, in addition to
      the 3D model generation, RealityConvert also generates image trackers, useful to
      universally call and anchor that particular 3D model when used in AR
      applications. The ultimate goal of RealityConvert is to facilitate and boost the
      development and accessibility of AR and VR contents for bioinformatics and
      cheminformatics applications. Availability and implementation:
      http://www.realityconvert.com. Contact: dfourch@ncsu.edu. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29036296
TI  - Unintended adverse consequences of a clinical decision support system: two cases.
AB  - Many institutions have implemented clinical decision support systems (CDSSs).
      While CDSS research papers have focused on benefits of these systems, there is a
      smaller body of literature showing that CDSSs may also produce unintended adverse
      consequences (UACs). Detailed here are 2 cases of UACs resulting from a CDSS.
      Both of these cases were related to external systems that fed data into the CDSS.
      In the first case, lack of knowledge of data categorization in an external
      pharmacy system produced a UAC; in the second case, the change of a clinical
      laboratory instrument produced the UAC. CDSSs rely on data from many external
      systems. These systems are dynamic and may have changes in hardware, software,
      vendors, or processes. Such changes can affect the accuracy of CDSSs. These cases
      point to the need for the CDSS team to be familiar with these external systems.
      This team (manager and alert builders) should include members in specific
      clinical specialties with deep knowledge of these external systems.

PMID- 29036293
TI  - Rare germline variants in known melanoma susceptibility genes in familial
      melanoma.
AB  - Known high-risk cutaneous malignant melanoma (CMM) genes account for melanoma
      risk in <40% of melanoma-prone families, suggesting the existence of additional
      high-risk genes or perhaps a polygenic mechanism involving multiple genetic
      modifiers. The goal of this study was to systematically characterize rare
      germline variants in 42 established melanoma genes among 144 CMM patients in 76
      American CMM families without known mutations using data from whole-exome
      sequencing. We identified 68 rare (<0.1% in public and in-house control datasets)
      nonsynonymous variants in 25 genes. We technically validated all loss-of
      function, inframe insertion/deletion, and missense variants predicted as
      deleterious, and followed them up in 1, 559 population-based CMM cases and 1, 633
      controls. Several of these variants showed disease co-segregation within
      families. Of particular interest, a stopgain variant in TYR was present in five
      of six CMM cases/obligate gene carriers in one family and a single population
      based CMM case. A start gain variant in the 5'UTR region of PLA2G6 and a missense
      variant in ATM were each seen in all three affected people in a single family,
      respectively. Results from rare variant burden tests showed that familial and
      population-based CMM patients tended to have higher frequencies of rare germline
      variants in albinism genes such as TYR, TYRP1, and OCA2 (P < 0.05). Our results
      suggest that rare nonsynonymous variants in low- or intermediate-risk CMM genes
      may influence familial CMM predisposition, warranting further investigation of
      both common and rare variants in genes affecting functionally important pathways
      (such as melanogenesis) in melanoma risk assessment.

PMID- 29036295
TI  - Psychotropic medications prescribing trends in adolescents: A nationwide
      population-based study in Taiwan.
AB  - Objective: To describe psychotropic medications prescription patterns among
      adolescents in Taiwan; focusing on age, gender, duration of treatments and
      various classes of psychotropic medications. Design: A retrospective description
      analysis. Setting: Taiwan National Health Insurance Database. Participants:
      Twelve to seventeen years' patients treated with psychotropic medications.
      Intervention: None. Main Outcome Measure(s): Percentage and duration of treatment
      with psychotropic medications during the study periods by medication classes and
      age groups were calculated. In addition, top three prescribed psychotropic
      medications were also determined. Results: A total of 3,120 patients were
      prescribed psychotropic drugs. The percentage of adolescent patients that
      received anxiolytics and antidepressants in 2002-2012 were 2.89% and 2.15%,
      respectively. Also, 851 patients (1.21%) were prescribed hypnotics and 638
      (0.91%) were given sedatives. The prevalence rate of the prescription of
      psychotropic drugs increased steadily with age and females were more treated than
      males except antipsychotic. Among psychotropic drugs, antidepressants (mean: 8.6
      times) were refilled more but antipsychotics (mean 188 days) were the long-term
      treatment drugs. Additionally, the trend of hospital visits fluctuated over the
      year while May and December showed a higher rate of visits. Conclusions: These
      findings show that the prevalence of psychotropic drug prescriptions in Taiwanese
      adolescents is even low but increasing trends in the prescription of these
      medications raises some concern. As the evidence of psychotropic drug safety and
      effectiveness in adolescents is still inadequate; we recommend that healthcare
      providers should consider psychotropic drugs therapy, continuously monitor for
      outcomes and empower their patients to improve their knowledge, therapeutic
      outcomes and quality of life.

PMID- 29036298
TI  - myVCF: a desktop application for high-throughput mutations data management.
AB  - Summary: Next-generation sequencing technologies have become the most powerful
      tool to discover genetic variants associated with human diseases. Although the
      dramatic reductions in the costs facilitate the use in the wet-lab and clinics,
      the huge amount of data generated renders their management by non-expert
      researchers and physicians extremely difficult. Therefore, there is an urgent
      need of novel approaches and tools aimed at getting the 'end-users' closer to the
      sequencing data, facilitating the access by non-bioinformaticians, and to speed
      up the functional interpretation of genetic variants. We developed myVCF, a
      standalone, easy-to-use desktop application, which is based on a browser
      interface and is suitable for Windows, Mac and UNIX systems. myVCF is an
      efficient platform that is able to manage multiple sequencing projects created
      from VCF files within the system; stores genetic variants and samples genotypes
      from an annotated VCF files into a SQLite database; implements a flexible search
      engine for data exploration, allowing to query for chromosomal region, gene,
      single variant or dbSNP ID. Besides, myVCF generates a summary statistics report
      about mutations distribution across samples and across the genome/exome by
      aggregating the information within the VCF file. In summary, the myVCF platform
      allows end-users without strong programming and bioinformatics skills to explore,
      query, visualize and export mutations data in a simple and straightforward way.
      Availability and implementation: https://apietrelli.github.io/myVCF/. Contact:
      pietrelli@ingm.org. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29036299
TI  - Libraries as 'everyday' settings: the Glasgow MCISS project.

PMID- 29036297
TI  - Genetic Evidence for Sexuality in Cochliopodium (Amoebozoa).
AB  - Microbial eukaryotes, including amoeboids, display diverse and complex life
      cycles that may or may not involve sexual reproduction. A recent comprehensive
      gene inventory study concluded that the Amoebozoa are ancestrally sexual.
      However, the detection of sex genes in some lineages known for their potentially
      sexual life cycle was very low. Particularly, the genus Cochliopodium, known to
      undergo a process of cell fusion, karyogamy, and subsequent fission previously
      described as parasexual, had no meiosis genes detected. This is likely due to low
      data representation, given the extensive nuclear fusion observed in the genus. In
      this study, we generate large amounts of transcriptome data for 2 species of
      Cochliopodium, known for their high frequency of cellular and nuclear fusion, in
      order to study the genetic basis of the complex life cycle observed in the genus.
      We inventory 60 sex-related genes, including 11 meiosis-specific genes, and 31
      genes involved in fusion and karyogamy. We find a much higher detection of sex
      related genes, including 5 meiosis-specific genes not previously detected in
      Cochliopodium, in this large transcriptome data. The expressed genes form a near
      complete recombination machinery, indicating that Cochliopodium is an actively
      recombining sexual lineage. We also find 9 fusion-related genes in Cochliopodium,
      although no conserved fusion-specific genes were detected in the transcriptomes.
      Cochliopodium thus likely uses lineage specific genes for the fusion and
      depolyploidization processes. Our results demonstrate that Cochliopodium possess
      the genetic toolkit for recombination, while the mechanism involving fusion and
      genome reduction remains to be elucidated.

PMID- 29036300
TI  - Bayesian hierarchical modeling based on multisource exchangeability.
AB  - Bayesian hierarchical models produce shrinkage estimators that can be used as the
      basis for integrating supplementary data into the analysis of a primary data
      source. Established approaches should be considered limited, however, because
      posterior estimation either requires prespecification of a shrinkage weight for
      each source or relies on the data to inform a single parameter, which determines
      the extent of influence or shrinkage from all sources, risking considerable bias
      or minimal borrowing. We introduce multisource exchangeability models (MEMs), a
      general Bayesian approach for integrating multiple, potentially non-exchangeable,
      supplemental data sources into the analysis of a primary data source. Our
      proposed modeling framework yields source-specific smoothing parameters that can
      be estimated in the presence of the data to facilitate a dynamic multi-resolution
      smoothed estimator that is asymptotically consistent while reducing the
      dimensionality of the prior space. When compared with competing Bayesian
      hierarchical modeling strategies, we demonstrate that MEMs achieve approximately
      2.2 times larger median effective supplemental sample size when the supplemental
      data sources are exchangeable as well as a 56% reduction in bias when there is
      heterogeneity among the supplemental sources. We illustrate the application of
      MEMs using a recently completed randomized trial of very low nicotine content
      cigarettes, which resulted in a 30% improvement in efficiency compared with the
      standard analysis.

PMID- 29036301
TI  - The Content Analysis of Gastrodin and Gastrodigenin Obtained by Different
      Processing Methods.
AB  - The purpose of this article was to investigate the effects of different
      processing methods on the content of gastrodin and gastrodigenin in Gastrodia
      elata Blume, so as to obtain the best processing method of G. elata. The contents
      of gastrodin and gastrodigenin in the samples were determined by HPLC method in
      turn. The results showed that the content of gastrodin and gastrodigenin were the
      highest in the sample obtained by extraction with 50% ethanol after boiling.
      Therefore, according to the two indexes of gastrodin and gastrodigenin, alcohol
      extraction after boiling was the best processing method, which could provide the
      reference for production.

PMID- 29036302
TI  - A prospective observational study to investigate utility of the Delirium
      Observational Screening Scale (DOSS) to detect delirium in care home residents.
AB  - Background: care home residents are particularly at risk of delirium due to high
      prevalence of dementia. The Delirium Observation Screening Scale (DOSS)
      identifies behavioural changes associated delirium onset that nursing staff are
      uniquely placed to recognise. We tested the psychometric properties of the DOSS
      in UK care homes compared with the Confusion Assessment Method (CAM). Design:
      prospective observational cohort study performed between 1 March 2015 and 30 June
      2016. Setting: nine UK residential and nursing care homes. Subjects: residents
      over 65 years except those approaching end of life or unable to complete delirium
      assessments. Methods: the 25-item DOSS was completed daily by care home staff and
      compared with the temporally closest CAM performed twice per week by trained
      researchers. Sensitivity, specificity, positive and negative predictive values,
      diagnostic odds and likelihood ratios were calculated. Results: 216 residents
      participated; mean age 84.9 (SD 7.9); 50% had cognitive impairment (median AMTS 7
      (IQR 3-9)). Half of all expected DOSS assessments occurred (30,201); of these,
      11,659 (39%) were complete. 78 positive CAM measurements were made during 71
      delirium episodes in 45 residents over 70 weeks. Sensitivity and specificity for
      delirium detection were optimised at a DOSS cut point of >=5 (sensitivity 0.61
      (95% CI: 0.39-0.80) and specificity (0.71 95% CI: 0.70-0.73)). Positive and
      negative predictive values were 1.6 and 99.5%, respectively. Conclusions: the low
      sensitivity of the DOSS limits clinical utility for detection of delirium as part
      of routine care for care home residents, although a negative DOSS affords
      confidence that delirium is not present.

PMID- 29036303
TI  - The safety and efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel
      in the treatment of non-small cell lung cancer patients with interstitial lung
      disease.
AB  - Background: The optimal chemotherapy regimen for non-small cell lung cancer
      patients with interstitial lung disease is unclear. We therefore investigated the
      safety and efficacy of carboplatin plus nab-paclitaxel as a first-line regimen
      for non-small cell lung cancer in patients with interstitial lung disease.
      Methods: We retrospectively reviewed advanced non-small cell lung cancer patients
      with interstitial lung disease who received carboplatin plus nab-paclitaxel as a
      first-line chemotherapy regimen at Hyogo Cancer Center between February 2013 and
      August 2016. interstitial lung disease was diagnosed according to the findings of
      pretreatment chest high-resolution computed tomography. Results: Twelve patients
      were included (male, n = 11; female, n = 1). The overall response rate was 67%
      and the disease control rate was 100%. The median progression free survival was
      5.1 months (95% CI: 2.9-8.3 months) and the median overall survival was 14.9
      months (95% CI: 4.8-not reached). A chemotherapy-related acute exacerbation of
      interstitial lung disease was observed in one patient; the extent of this event
      was Grade 2. There were no treatment-related deaths. Conclusions: Carboplatin
      plus nab-paclitaxel, as a first-line chemotherapy regimen for non-small cell lung
      cancer, showed favorable efficacy and safety in patients with preexisting
      interstitial lung disease.

PMID- 29036304
TI  - IL-1R and MyD88 signalling in CD4+ T cells promote Th17 immunity and
      atherosclerosis.
AB  - Aims: The role of CD4+ T cells in atherosclerosis has been shown to be dependent
      on cytokine cues that regulate lineage commitment into mature T helper sub-sets.
      In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4+ T cells
      in atherosclerosis. Methods and results: We transferred apoe-/-myd88+/+ or apoe-/
      myd88-/- CD4+ T cells to T- and B-cell-deficient rag1-/-apoe-/- mice fed high fat
      diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis
      compared with mice given apoe-/-myd88+/+ CD4+ T cells. CD4+ T cells from apoe-/
      myd88-/- produced less IL-17 but similar levels of IFN-gamma. Treatment of human
      CD4+ T cells with a MyD88 inhibitor inhibited IL-17 secretion in vitro. Transfer
      of il1r1-/- CD4+ T cells recapitulated the phenotype seen by transfer of myd88-/-
      CD4+ T cells with reduced lesion development and a reduction in Th17 and IL-17
      production compared with wild type CD4+ T cell recipients. Relative collagen
      content of lesions was reduced in mice receiving il1r1-/- CD4+ T cells.
      Conclusion: We demonstrate that both IL1R and MyD88 signalling in CD4+ T cells
      promote Th17 immunity, plaque growth and may regulate plaque collagen levels.

PMID- 29036305
TI  - Breeding for cuticle-associated traits in crop species: traits, targets, and
      strategies.
AB  - Improving crop productivity and quality while promoting sustainable agriculture
      have become major goals in plant breeding. The cuticle is a natural film covering
      the aerial organs of plants and consists of lipid polyesters covered and embedded
      with wax. The cuticle protects plants against water loss and pathogens and
      affects traits with strong impacts on crop quality such as, for horticultural
      crops, fruit brightness, cracking, russeting, netting, and shelf life. Here we
      provide an overview of the most important cuticle-associated traits that can be
      targeted for crop improvement. To date, most studies on cuticle-associated traits
      aimed at crop breeding have been done on fleshy fruits. Less information is
      available for staple crops such as rice, wheat or maize. Here we present new
      insights into cuticle formation and properties resulting from the study of
      genetic resources available for the various crop species. Our review also covers
      the current strategies and tools aimed at exploiting available natural and
      artificially induced genetic diversity and the technologies used to transfer the
      beneficial alleles affecting cuticle-associated traits to commercial varieties.

PMID- 29036306
TI  - CXXC5 suppresses hepatocellular carcinoma by promoting TGF-beta-induced cell
      cycle arrest and apoptosis.
AB  - Evading TGF-beta-mediated growth inhibition is often associated with
      tumorigenesis in liver, including hepatocellular carcinoma (HCC). To better
      understand the functions and the underlying molecular mechanisms of TGF-beta in
      HCC initiation and progression, we carried out transcriptome sequencing (RNA-Seq)
      to identify the target genes of TGF-beta. CXXC5, a member of the CXXC-type zinc
      finger domain-containing protein family, was identified as a novel TGF-beta
      target gene in Hep3B HCC cells. Knockdown of CXXC5 attenuated the expression of a
      substantial portion of TGF-beta target genes and ameliorated TGF-beta-induced
      growth inhibition or apoptosis of Hep3B cells, suggesting that CXXC5 is required
      for TGF-beta-mediated inhibition of HCC progression. Analysis of the TCGA
      database indicated that CXXC5 expression is reduced in the majority of HCC tissue
      samples in comparison to that in normal tissues. Furthermore, CXXC5 associates
      with the histone deacetylase HDAC1 and competes its interaction with Smad2/3,
      thereby abolishing the inhibitory effect of HDAC1 on TGF-beta signaling. These
      observations together suggest that CXXC5 may act as a tumor suppressor by
      promoting TGF-beta signaling via a positive feedback loop, and reveal a strategy
      for HCC to bypass TGF-beta-mediated cytostasis by disrupting the positive
      feedback regulation. Our findings shed new light on TGF-beta signaling regulation
      and demonstrate the function of CXXC5 in HCC development.

PMID- 29036307
TI  - Irys Extract.
AB  - Summary: Irys Extract is a software tool for generating genomic information from
      data collected by the BioNano Genomics Irys platform. The tool allows the user
      easy access to the raw data in the form of cropped images and genetically aligned
      intensity profiles. The latter are also made compatible with the BED format for
      using with popular genomic browsers such as the UCSC Genome Browser. Availability
      and implementation: Irys Extract has been developed in Matlab R2015a, it was
      tested to work with IrysView 2.4.0.15879 and AutoDetect 2.1.4.9159, and it
      currently runs under Microsoft Windows operating systems (7-10). Irys Extract can
      be downloaded alongside its manual and a demo dataset at
      http://www.nanobiophotonix.com and https://sites.google.com/site/raniarielly/.
      Contact: uv@post.tau.ac.il. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29036308
TI  - High prevalence of arrhythmic and myocardial complications in patients with
      cardiac glycogenosis due to PRKAG2 mutations: comment.

PMID- 29036309
TI  - Chiral Analysis of Methamphetamine in Oral Fluid Samples: A Method to Distinguish
      Licit from Illicit Drug Use.
AB  - Methamphetamine (MAMP) is a popular illicit drug abused for its central nervous
      system stimulating effects. MAMP is also used therapeutically in the treatment of
      overeating disorders, narcolepsy, attention deficit disorder, in over-the-counter
      (OTC) products to ease nasal congestion. MAMP exists in two enantiomeric forms,
      dextrorotary (d-MAMP) or levorotary (l-MAMP). The compounds are similar in
      chemical structure, simply differing in the orientation of functional groups
      around the asymmetric carbon. In part because of the availability of l-MAMP in
      OTC nasal inhalers, forensic guidelines require a sample to contain greater than
      20% d-MAMP to consider illicit drug use when interpreting results. Standard
      analytical methods readily detect MAMP in biological specimens but cannot resolve
      the enantiomeric composition of the sample. Specialized analytical techniques
      based on chiral separation of the enantiomers are required to differentiate d
      MAMP from l-MAMP. Our laboratory sought to develop and validate a method for the
      analysis of oral fluid specimens for d/l-MAMP using a chiral derivatizing agent
      and traditional reverse phase liquid chromatography tandem mass spectrometry (LC
      MS-MS). MAMP was extracted from dilute oral fluid samples using Strata-XC solid
      phase extraction (SPE) cartridges and derivatized with Marfey's reagent.
      Chromatographic separation was achieved using Zorbax Eclipse Plus C18 columns.
      Linearity, accuracy and precision, recovery, matrix effects and specificity of
      the method were all within acceptable criteria. Intraday accuracy ranged from
      93.3 to 103.4% and precision 0.1 to 1.6%. Interday accuracy ranged from 90.0 to
      103.4% and precision 3.8 to 11.6%. Finally, having previously tested positive for
      MAMP using non-chiral analysis, 256 de-identified authentic oral fluid samples
      were analyzed using this validated method. 98% of all samples tested positive for
      d-MAMP at greater than 20%.

PMID- 29036310
TI  - Baclofen Self-Poisoning in the Era of Changing Indication: Multicentric Reports
      to a French Poison Control Centre.
AB  - Aims: Baclofen has gained interest in treating alcohol use disorder patients.
      These patients are at risk of voluntary drug intoxications. Understanding the
      context of baclofen's widespread use for alcohol use disorder, a recent
      evaluation of the epidemiology, morbidity and mortality of baclofen self
      poisoning episodes is necessary. Methods: All baclofen self-poisoning reported to
      the Western France Poison Control Centre between January 2008 and December 2015
      were included for analysis in this retrospective study. Baclofen poisoning cases
      were compared to the 31,859 non-baclofen voluntary poisoning cases declared over
      the same period. Results: Number of baclofen poisoning grew from 8 cases in 2008
      to 91 cases in 2015, attributable to patients purposely treated for alcohol use
      disorder. Overall, 190 cases were considered: 111 patients (59%) had Glasgow coma
      score (GCS) <=12 at hospital admission and 77 had GCS > 12 (41%). Eighty patients
      required mechanical ventilation (42.6%). Neurological severity (GCS <= 12) was
      associated with seizures (n = 24, 22% vs. n = 2, 3%, P < 0.001). Two patients
      were deceased at first medical evaluation and three died in the hospital
      (mortality rate 2.6%). Non-baclofen cases had lower rate of endotracheal
      intubation (n = 1833, 6%, P < 0.001) and mortality rate (n = 299, 0.1%, P =
      0.02). Conclusions: Baclofen self-poisoning cases has risen in recent years due
      to baclofen intake for alcohol use disorder therapies. The risk-benefit ratio may
      be evaluated before baclofen is safely prescribed.

PMID- 29036311
TI  - Do work and family care histories predict health in older women?
AB  - Background: Social and policy changes in the last several decades have increased
      women's options for combining paid work with family care. We explored whether
      specific combinations of work and family care over the lifecourse are associated
      with variations in women's later life health. Methods: We used sequence analysis
      to group women in the English Longitudinal Study of Ageing according to their
      work histories and fertility. Using logistic regression, we tested for group
      differences in later life disability, depressive symptomology and mortality,
      while controlling for childhood health and socioeconomic position and a range of
      adult socio-economic circumstances and health behaviours. Results: Women who
      transitioned from family care to either part-time work after a short break from
      the labour force, or to full-time work, reported lower odds of having a
      disability compared with the reference group of women with children who were
      mostly employed full-time throughout. Women who shifted from family care to part
      time work after a long career break had lower odds of mortality than the
      reference group. Depressive symptoms were not associated with women's work and
      family care histories. Conclusion: Women's work histories are predictive of their
      later life disability and mortality. This relationship may be useful in targeting
      interventions aimed at improving later life health. Further research is necessary
      to explore the mechanisms linking certain work histories to poorer later life
      health and to design interventions for those affected.

PMID- 29036312
TI  - Safety and efficacy of cryoablation vs. radiofrequency ablation of septal
      accessory pathways: systematic review of the literature and meta-analyses.
AB  - Aims: Radiofrequency ablation (RFA) of septal accessory pathways (APs) is
      associated with a significant rate of first procedure failures and complications.
      Cryoablation is an alternative energy source but there are no studies comparing
      both ablation techniques. We aimed to systematically review the literature and
      compare the efficacy and safety of cryoablation vs. RFA of septal APs. Methods
      and results: We conducted two separate meta-analysis of cryoablation and RFA of
      septal APs and calculated the global estimates of the efficacy and safety. Sixty
      four articles were included: 38 articles reporting RFA and 27 articles reporting
      cryoablation procedures. Additionally, we included the previously non-published
      cryoablation registry of septal APs performed at our institution. Overall, 4244
      septal APs constitute our study population, 3495 in the RFA cohort and 749 in the
      cryoablation cohort. Acute procedural success rate of cryoablation was 86.0% (95%
      CI 81.6-89.4%) and RFA 89.0% (95% CI 86.8-91.0%). Recurrence rate of cryoablation
      was 18.1% (95% CI 14.8-21.8%) and RFA 9.9% (95% CI 8.2-12.0%). Long-term success
      rate after multiple ablation procedures of cryoablation was 75.9% (95% CI 68.2
      82.3%) and RFA 88.4% (95% CI 84.7-91.3%). There were no reported cases of
      persistent atrioventricular block (AVB) with cryoablation and 2.7% (95% CI 2.2
      3.4%) with RFA. Conclusion: Studies of RFA for treatment of septal APs report
      higher efficacy rates than do studies using cryoablation, but a significantly
      higher rate of AVB.

PMID- 29036313
TI  - High Interspecimen Variability in Nucleic Acid Extraction Efficiency Necessitates
      the Use of Spike-In Control for Accurate qPCR-based Measurement of Plasma Cell
      Free DNA Levels.
AB  - Objective: To assess the interspecimen variability associated with plasma DNA
      extraction in order to provide insight regarding the necessity to use an
      exogenous spike-in control when measuring cell-free DNA (cfDNA) levels using
      quantitative polymerase chain reaction (qPCR). Methods: Plasma specimens were
      obtained from 8 healthy individuals, 20 patients with cardiovascular disease risk
      factors, and 54 patients diagnosed with acute stroke. Specimens were spiked with
      an exogenous oligonucleotide fragment, and total DNA was extracted via automated
      solid phase anion exchange. We determined recovery of the exogenous fragment via
      qPCR and used this information to calculate DNA extraction efficiency. Results:
      Plasma DNA extraction efficiencies varied dramatically between specimens, ranging
      from 22.9% to 88.1%, with a coefficient of variance of 28.9%. No significant
      differences in DNA extraction efficiencies were observed between patient
      populations. Conclusions: We strongly recommend the use of an exogenous spike-in
      control to account for variance in plasma DNA extraction efficiency when
      assessing cell free DNA (cfDNA) levels by qPCR in future biomarker
      investigations.

PMID- 29036315
TI  - Probabilistic Modeling Approach to Reducing Healthcare Costs With Reflex Testing.
AB  - Objective: Statistical methods can be utilized to optimize the order for reflex
      diagnostic testing to attenuate patient and hospital costs without affecting
      quality of care. Our objective is to demonstrate the method of developing an
      order for testing and to apply this method to an illustrative example. Methods:
      An algorithm was developed for minimizing costs for any given number of
      diagnostic tests, and it was retrospectively applied to a sample. Results: The
      actual scenario of using both tests on all patients was compared to 2 other
      hypothetical reflex testing approaches: all patients are given 1 test, and those
      patients who tested negative were then given the second test. The 2 scenarios
      would have saved 37.1% and 17.4% in testing costs, respectively. Conclusion:
      These calculations could be applied to numerous situations to reduce costs for
      patients and hospitals. We propose that this methodology would be best used in
      conjunction with any existing quality improvement initiatives.

PMID- 29036314
TI  - Mirnovo: genome-free prediction of microRNAs from small RNA sequencing data and
      single-cells using decision forests.
AB  - The discovery of microRNAs (miRNAs) remains an important problem, particularly
      given the growth of high-throughput sequencing, cell sorting and single cell
      biology. While a large number of miRNAs have already been annotated, there may
      well be large numbers of miRNAs that are expressed in very particular cell types
      and remain elusive. Sequencing allows us to quickly and accurately identify the
      expression of known miRNAs from small RNA-Seq data. The biogenesis of miRNAs
      leads to very specific characteristics observed in their sequences. In brief,
      miRNAs usually have a well-defined 5' end and a more flexible 3' end with the
      possibility of 3' tailing events, such as uridylation. Previous approaches to the
      prediction of novel miRNAs usually involve the analysis of structural features of
      miRNA precursor hairpin sequences obtained from genome sequence. We surmised that
      it may be possible to identify miRNAs by using these biogenesis features observed
      directly from sequenced reads, solely or in addition to structural analysis from
      genome data. To this end, we have developed mirnovo, a machine learning based
      algorithm, which is able to identify known and novel miRNAs in animals and plants
      directly from small RNA-Seq data, with or without a reference genome. This method
      performs comparably to existing tools, however is simpler to use with reduced run
      time. Its performance and accuracy has been tested on multiple datasets,
      including species with poorly assembled genomes, RNaseIII (Drosha and/or Dicer)
      deficient samples and single cells (at both embryonic and adult stage).

PMID- 29036317
TI  - Quality of local school wellness policies for physical activity and resultant
      implementation in Pennsylvania schools.
AB  - Background: In 2006, United States public schools participating in federal school
      meal programs were required to adopt school wellness policies. The effect of
      these policies on school nutrition environments is well documented; however,
      evaluation of physical activity policies has received less investigation. We
      aimed to evaluate how district wellness policies aligned to practice for physical
      activity implementation in 40 schools with high obesity rates (>24%). Methods:
      Wellness policies were evaluated using the validated Wellness School Assessment
      Tool (WellSAT). Concurrently, schools completed the validated Alliance for a
      Healthier Generation's Healthy Schools Program (HSP) self-assessment to evaluate
      physical activity practices. Overall, 13 of 20 physical activity measures from
      WellSAT and 12 of 13 physical activity measures from HSP were aligned to match
      policy with practice. Results: Most policy items scored 0 or 1, indicating either
      'no mention in the policy' or 'containing weak or vague language'. Corresponding
      HSP results indicated that school physical activity practices are 'not in place'
      or 'under development'. A strong, positive, correlation (r = 0.92, P < 0.001)
      indicated that a significant relationship exists between policy and
      implementation. Conclusions: Results indicate that most districts currently have
      weak policies regarding physical activity, limiting the potential to positively
      influence school-based physical activity.

PMID- 29036316
TI  - The Role of Small RNA-Based Epigenetic Silencing for Purifying Selection on
      Transposable Elements in Capsella grandiflora.
AB  - To avoid negative effects of transposable element (TE) proliferation, plants
      epigenetically silence TEs using a number of mechanisms, including RNA-directed
      DNA methylation. These epigenetic modifications can extend outside the boundaries
      of TE insertions and lead to silencing of nearby genes, resulting in a trade-off
      between TE silencing and interference with nearby gene regulation. Therefore,
      purifying selection is expected to remove silenced TE insertions near genes more
      efficiently and prevent their accumulation within a population. To explore how
      effects of TE silencing on gene regulation shapes purifying selection on TEs, we
      analyzed whole genome sequencing data from 166 individuals of a large population
      of the outcrossing species Capsella grandiflora. We found that most TEs are rare,
      and in chromosome arms, silenced TEs are exposed to stronger purifying selection
      than those that are not silenced by 24-nucleotide small RNAs, especially with
      increasing proximity to genes. An age-of-allele test of neutrality on a subset of
      TEs supports our inference of purifying selection on silenced TEs, suggesting
      that our results are robust to varying transposition rates. Our results provide
      new insights into the processes affecting the accumulation of TEs in an
      outcrossing species and support the view that epigenetic silencing of TEs results
      in a trade-off between preventing TE proliferation and interference with nearby
      gene regulation. We also suggest that in the centromeric and pericentromeric
      regions, the negative aspects of epigenetic TE silencing are missing.

PMID- 29036318
TI  - DIMM-SC: a Dirichlet mixture model for clustering droplet-based single cell
      transcriptomic data.
AB  - Motivation: Single cell transcriptome sequencing (scRNA-Seq) has become a
      revolutionary tool to study cellular and molecular processes at single cell
      resolution. Among existing technologies, the recently developed droplet-based
      platform enables efficient parallel processing of thousands of single cells with
      direct counting of transcript copies using Unique Molecular Identifier (UMI).
      Despite the technology advances, statistical methods and computational tools are
      still lacking for analyzing droplet-based scRNA-Seq data. Particularly, model
      based approaches for clustering large-scale single cell transcriptomic data are
      still under-explored. Results: We developed DIMM-SC, a Dirichlet Mixture Model
      for clustering droplet-based Single Cell transcriptomic data. This approach
      explicitly models UMI count data from scRNA-Seq experiments and characterizes
      variations across different cell clusters via a Dirichlet mixture prior. We
      performed comprehensive simulations to evaluate DIMM-SC and compared it with
      existing clustering methods such as K-means, CellTree and Seurat. In addition, we
      analyzed public scRNA-Seq datasets with known cluster labels and in-house scRNA
      Seq datasets from a study of systemic sclerosis with prior biological knowledge
      to benchmark and validate DIMM-SC. Both simulation studies and real data
      applications demonstrated that overall, DIMM-SC achieves substantially improved
      clustering accuracy and much lower clustering variability compared to other
      existing clustering methods. More importantly, as a model-based approach, DIMM-SC
      is able to quantify the clustering uncertainty for each single cell, facilitating
      rigorous statistical inference and biological interpretations, which are
      typically unavailable from existing clustering methods. Availability and
      implementation: DIMM-SC has been implemented in a user-friendly R package with a
      detailed tutorial available on www.pitt.edu/~wec47/singlecell.html. Contact:
      wei.chen@chp.edu or hum@ccf.org. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 29036319
TI  - Discovery of susceptibility loci associated with tuberculosis in Han Chinese.
AB  - Genome-wide association studies (GWASs) have revealed the worldwide heterogeneity
      of genetic factors in tuberculosis (TB) susceptibility. Despite having the third
      highest global TB burden, no TB-related GWAS has been performed in China. Here,
      we performed the first three-stage GWAS on TB in the Han Chinese population. In
      the stage 1 (discovery stage), after quality control, 691 388 SNPs present in 972
      TB patients and 1537 controls were retained. After replication on an additional
      3460 TB patients and 4862 controls (stages 2 and 3), we identified three
      significant loci associated with TB, the most significant of which was rs4240897
      (logistic regression P = 1.41 * 10-11, odds ratio = 0.79). The aforementioned
      three SNPs were harbored by MFN2, RGS12 and human leukocyte antigen class II beta
      chain paralogue encoding genes, all of which are candidate immune genes
      associated with TB. Our findings provide new insight into the genetic background
      of TB in the Han Chinese population.

PMID- 29036320
TI  - Detect differentially methylated regions using non-homogeneous hidden Markov
      model for methylation array data.
AB  - Motivation: DNA methylation is an important epigenetic mechanism in gene
      regulation and the detection of differentially methylated regions (DMRs) is
      enthralling for many disease studies. There are several aspects that we can
      improve over existing DMR detection methods: (i) methylation statuses of nearby
      CpG sites are highly correlated, but this fact has seldom been modelled
      rigorously due to the uneven spacing; (ii) it is practically important to be able
      to handle both paired and unpaired samples; and (iii) the capability to detect
      DMRs from a single pair of samples is demanded. Results: We present DMRMark (DMR
      detection based on non-homogeneous hidden Markov model), a novel Bayesian
      framework for detecting DMRs from methylation array data. It combines the
      constrained Gaussian mixture model that incorporates the biological knowledge
      with the non-homogeneous hidden Markov model that models spatial correlation.
      Unlike existing methods, our DMR detection is achieved without predefined
      boundaries or decision windows. Furthermore, our method can detect DMRs from a
      single pair of samples and can also incorporate unpaired samples. Both simulation
      studies and real datasets from The Cancer Genome Atlas showed the significant
      improvement of DMRMark over other methods. Availability and implementation:
      DMRMark is freely available as an R package at the CRAN R package repository.
      Contact: xfan@cuhk.edu.hk. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29036321
TI  - Vitamin B12 ameliorates the phenotype of a mouse model of DiGeorge syndrome.

PMID- 29036322
TI  - tGBS(r) genotyping-by-sequencing enables reliable genotyping of heterozygous
      loci.
AB  - Conventional genotyping-by-sequencing (cGBS) strategies suffer from high rates of
      missing data and genotyping errors, particularly at heterozygous sites. tGBS(r)
      genotyping-by-sequencing is a novel method of genome reduction that employs two
      restriction enzymes to generate overhangs in opposite orientations to which
      (single-strand) oligos rather than (double-stranded) adaptors are ligated. This
      strategy ensures that only double-digested fragments are amplified and sequenced.
      The use of oligos avoids the necessity of preparing adaptors and the problems
      associated with inter-adaptor annealing/ligation. Hence, the tGBS protocol
      simplifies the preparation of high-quality GBS sequencing libraries. During
      polymerase chain reaction (PCR) amplification, selective nucleotides included at
      the 3'-end of the PCR primers result in additional genome reduction as compared
      to cGBS. By adjusting the number of selective bases, different numbers of genomic
      sites are targeted for sequencing. Therefore, for equivalent amounts of
      sequencing, more reads per site are available for SNP calling. Hence, as compared
      to cGBS, tGBS delivers higher SNP calling accuracy (>97-99%), even at
      heterozygous sites, less missing data per marker across a population of samples,
      and an enhanced ability to genotype rare alleles. tGBS is particularly well
      suited for genomic selection, which often requires the ability to genotype
      populations of individuals that are heterozygous at many loci.

PMID- 29036323
TI  - Structural basis for the specific recognition of 18S rRNA by APUM23.
AB  - PUF (Pumilio/fem-3 mRNA binding factor) proteins, a conserved family of RNA
      binding proteins, recognize specific single-strand RNA targets in a specific
      modular way. Although plants have a greater number of PUF protein members than do
      animal and fungal systems, they have been the subject of fewer structural and
      functional investigations. The aim of this study was to elucidate the involvement
      of APUM23, a nucleolar PUF protein in the plant Arabidopsis, in pre-rRNA
      processing. APUM23 is distinct from classical PUF family proteins, which are
      located in the cytoplasm and bind to 3'UTRs of mRNA to modulate mRNA expression
      and localization. We found that the complete RNA target sequence of APUM23
      comprises 11 nt in 18S rRNA at positions 1141-1151. The complex structure shows
      that APUM23 has 10 PUF repeats; it assembles into a C-shape, with an insertion
      located within the inner concave surface. We found several different RNA
      recognition features. A notable structural feature of APUM23 is an insertion in
      the third PUF repeat that participates in nucleotide recognition and maintains
      the correct conformation of the target RNA. Our findings elucidate the mechanism
      for APUM23's-specific recognition of 18S rRNA.

PMID- 29036325
TI  - It's all in the timing: calibrating temporal penalties for biomedical data
      sharing.
AB  - Objective: Biomedical science is driven by datasets that are being accumulated at
      an unprecedented rate, with ever-growing volume and richness. There are various
      initiatives to make these datasets more widely available to recipients who sign
      Data Use Certificate agreements, whereby penalties are levied for violations. A
      particularly popular penalty is the temporary revocation, often for several
      months, of the recipient's data usage rights. This policy is based on the
      assumption that the value of biomedical research data depreciates significantly
      over time; however, no studies have been performed to substantiate this belief.
      This study investigates whether this assumption holds true and the data science
      policy implications. Methods: This study tests the hypothesis that the value of
      data for scientific investigators, in terms of the impact of the publications
      based on the data, decreases over time. The hypothesis is tested formally through
      a mixed linear effects model using approximately 1200 publications between 2007
      and 2013 that used datasets from the Database of Genotypes and Phenotypes, a data
      sharing initiative of the National Institutes of Health. Results: The analysis
      shows that the impact factors for publications based on Database of Genotypes and
      Phenotypes datasets depreciate in a statistically significant manner. However, we
      further discover that the depreciation rate is slow, only ~10% per year, on
      average. Conclusion: The enduring value of data for subsequent studies implies
      that revoking usage for short periods of time may not sufficiently deter those
      who would violate Data Use Certificate agreements and that alternative penalty
      mechanisms may need to be invoked.

PMID- 29036324
TI  - PancanQTL: systematic identification of cis-eQTLs and trans-eQTLs in 33 cancer
      types.
AB  - Expression quantitative trait locus (eQTL) analysis, which links variations in
      gene expression to genotypes, is essential to understanding gene regulation and
      to interpreting disease-associated loci. Currently identified eQTLs are mainly in
      samples of blood and other normal tissues. However, no database comprehensively
      provides eQTLs in large number of cancer samples. Using the genotype and
      expression data of 9196 tumor samples in 33 cancer types from The Cancer Genome
      Atlas (TCGA), we identified 5 606 570 eQTL-gene pairs in the cis-eQTL analysis
      and 231 210 eQTL-gene pairs in the trans-eQTL analysis. We further performed
      survival analysis and identified 22 212 eQTLs associated with patient overall
      survival. Furthermore, we linked the eQTLs to genome-wide association studies
      (GWAS) data and identified 337 131 eQTLs that overlap with existing GWAS loci. We
      developed PancanQTL, a user-friendly database
      (http://bioinfo.life.hust.edu.cn/PancanQTL/), to store cis-eQTLs, trans-eQTLs,
      survival-associated eQTLs and GWAS-related eQTLs to enable searching, browsing
      and downloading. PancanQTL could help the research community understand the
      effects of inherited variants in tumorigenesis and development.

PMID- 29036326
TI  - Circular RNAs are abundant and dynamically expressed during embryonic muscle
      development in chickens.
AB  - The growth and development of skeletal muscle is regulated by proteins as well as
      non-coding RNAs. Circular RNAs (circRNAs) are universally expressed in various
      tissues and cell types, and regulate gene expression in eukaryotes. To identify
      the circRNAs during chicken embryonic skeletal muscle development, leg muscles of
      female Xinghua (XH) chicken at three developmental time points 11 embryo age
      (E11), 16 embryo age (E16) and 1 day post hatch (P1) were performed RNA
      sequencing. We identified 13,377 circRNAs with 3,036 abundantly expressed and
      most were derived from coding exons. A total of 462 differentially expressed
      circRNAs were identified (fold change > 2; q-value < 0.05). Parental genes of
      differentially expressed circRNAs were related to muscle biological processes.
      There were 946 exonic circRNAs have been found that harbored one or more miRNA
      binding site for 150 known miRNAs. We validated that circRBFOX2s promoted cell
      proliferation through interacted with miR-206. These data collectively indicate
      that circRNAs are abundant and dynamically expressed during embryonic muscle
      development and could play key roles through sequestering miRNAs as well as other
      functions.

PMID- 29036327
TI  - Measurement of incorporation kinetics of non-fluorescent native nucleotides by
      DNA polymerases using fluorescence microscopy.
AB  - We describe a method for measuring the single-turnover incorporation kinetics of
      non-fluorescent native nucleotides by DNA polymerases. Time-lapse total internal
      reflection fluorescence (TIRF) microscopy is used to directly measure the
      kinetics of single-base nucleotide incorporation into primed DNA templates
      covalently attached to the surface of a glass coverslip using a fixed ratio of a
      native nucleotide and a corresponding fluorescently labeled nucleotide over a
      series of total nucleotide concentrations. The presence of a labeled nucleotide
      allows for the kinetics of competitive incorporation reactions by DNA polymerase
      to be monitored. The single-turnover catalytic rate constants and Michaelis
      constants of the incorporation of the native nucleotides can be determined by
      modeling the kinetics of the parallel competitive reactions. Our method enables
      the measurements of the kinetics parameters of incorporation of native or other
      non-fluorescent nucleotides without using a rapid stopped-flow or quench-flow
      instrument and the generally more involved and less quantitative post-reaction
      analysis of the reaction products. As a demonstration of our method, we
      systematically determined the single-turnover incorporation kinetics of all four
      native nucleotides and a set of Cy3-labeled nucleotides by the Klenow fragment of
      Escherichia coli DNA polymerase I.

PMID- 29036328
TI  - Phylogeography and Population Genetic Analyses in the Iberian Toothcarp (Aphanius
      iberus Valenciennes, 1846) at Different Time Scales.
AB  - Secondary freshwater fish species inhabiting fluctuating and extreme environments
      are susceptible to changes in dispersion, effective population size, and genetic
      structure. The Iberian toothcarp Aphanius iberus is an endemic cyprinodontid of
      the Iberian Peninsula restricted to brackish water of salt marshes and coastal
      lagoons on the eastern Spanish Mediterranean coast. In this study, we analyzed
      mitochondrial cytochrome b (cyt b) DNA and microsatellite variation to evaluate
      ways in which the processes of extinction, dispersal, and colonization of A.
      iberus across its geographic distribution have affected its population genetic
      structure over time and space. The A. iberus network reconstruction indicated
      subtle levels of phylogeographic structuring. This, combined with substantial
      mitochondrial DNA (mtDNA) genetic diversity, suggests that Pleistocene
      glaciations had a lesser effect on the demographic structure of its populations
      than was the case for Iberian freshwater species with a similar distribution.
      Haplotype network, hierarchical analysis of molecular variance, and pairwise
      PhiST comparisons involving some Levantine samples showed a relatively high
      degree of mtDNA differentiation, which could be explained by historical isolation
      of the Villena Lagoon population. Conversely, significant genetic differentiation
      that follows an isolation-by-distance pattern, and a reduction in Ne though time
      was detected with microsatellites, suggesting extensive habitat fragmentation on
      the Mediterranean coast of the Iberian Peninsula over the past hundreds of years.
      At a smaller geographical scale (Mar Menor Lagoon), habitat fragmentation,
      probably due to human activity, appears to have resulted in substantially reduced
      migration and increased genetic drift, as shown by expanded genetic
      differentiation of populations.

PMID- 29036330
TI  - Adding experimental arms to platform clinical trials: randomization procedures
      and interim analyses.
AB  - Multi-arm clinical trials use a single control arm to evaluate multiple
      experimental treatments. In most cases this feature makes multi-arm studies
      considerably more efficient than two-arm studies. A bottleneck for implementation
      of a multi-arm trial is the requirement that all experimental treatments have to
      be available at the enrollment of the first patient. New drugs are rarely at the
      same stage of development. These limitations motivate our study of statistical
      methods for adding new experimental arms after a clinical trial has started
      enrolling patients. We consider both balanced and outcome-adaptive randomization
      methods for experimental designs that allow investigators to add new arms,
      discuss their application in a tuberculosis trial, and evaluate the proposed
      designs using a set of realistic simulation scenarios. Our comparisons include
      two-arm studies, multi-arm studies, and the proposed class of designs in which
      new experimental arms are added to the trial at different time points.

PMID- 29036329
TI  - m6AVar: a database of functional variants involved in m6A modification.
AB  - Identifying disease-causing variants among a large number of single nucleotide
      variants (SNVs) is still a major challenge. Recently, N6-methyladenosine (m6A)
      has become a research hotspot because of its critical roles in many fundamental
      biological processes and a variety of diseases. Therefore, it is important to
      evaluate the effect of variants on m6A modification, in order to gain a better
      understanding of them. Here, we report m6AVar (http://m6avar.renlab.org), a
      comprehensive database of m6A-associated variants that potentially influence m6A
      modification, which will help to interpret variants by m6A function. The m6A
      associated variants were derived from three different m6A sources including
      miCLIP/PA-m6A-seq experiments (high confidence), MeRIP-Seq experiments (medium
      confidence) and transcriptome-wide predictions (low confidence). Currently,
      m6AVar contains 16 132 high, 71 321 medium and 326 915 low confidence level m6A
      associated variants. We also integrated the RBP-binding regions, miRNA-targets
      and splicing sites associated with variants to help users investigate the effect
      of m6A-associated variants on post-transcriptional regulation. Because it
      integrates the data from genome-wide association studies (GWAS) and ClinVar,
      m6AVar is also a useful resource for investigating the relationship between the
      m6A-associated variants and disease. Overall, m6AVar will serve as a useful
      resource for annotating variants and identifying disease-causing variants.

PMID- 29036331
TI  - Early Reading Development in Chinese-speaking Children with Hearing Loss.
AB  - This study aims to explore early reading comprehension in Chinese-speaking
      children with hearing loss (HL) by examining character recognition and linguistic
      comprehension. Twenty-five children with HL received three measures relevant to
      character reading: phonological awareness (PA), morphological awareness (MA), and
      character recognition; two linguistic-comprehension measures: receptive
      vocabulary knowledge and listening comprehension; and one reading comprehension
      measure. Three demographic variables pertinent to children with HL were also
      taken into account. The results showed that the degree of HL was significantly
      related to reading comprehension, receptive vocabulary knowledge, and listening
      comprehension, the latter two of which were further correlated with the type of
      hearing device; however, the hearing age was associated with neither of the
      measures. MA made a unique contribution to character reading in the presence of
      PA, but the reverse was not true. Linguistic comprehension significantly
      accounted for additional variance in reading comprehension over and above
      character recognition but not vice versa. A further analysis controlling for
      character recognition revealed that receptive vocabulary knowledge was more
      contributive to early reading comprehension than was listening comprehension. The
      results of the current investigation have potential to inform educational
      practice in teaching and/or intervening Chinese children with HL regarding their
      reading skills.

PMID- 29036332
TI  - Sensitivity to Physical Activity Predicts Daily Activity Among Pain-Free Older
      Adults.
AB  - Objective: Prior research indicates that older adults with knee osteoarthritis
      have increased sensitivity to physical activity (SPA) and respond to physical
      activities of stable intensity with increases in pain. Whether SPA is present in
      healthy older adults without chronic pain and predicts functional outcomes
      remains relatively unexplored. The purpose of this study was to determine the
      degree of SPA in healthy older adults in response to a standardized walking task,
      and whether SPA was associated with temporal summation of pain, pain-related fear
      of movement, and functional outcomes. Methods: Fifty-two older adults without
      chronic pain completed self-reported measures of activity-related pain and
      physical function, completed the Six-Minute Walk Test (6MWT), underwent
      quantitative sensory testing to measure temporal summation of heat pain, and wore
      an accelerometer for one week to measure physical activity behavior. Subjects
      rated overall bodily discomfort (0-100 scale) prior to and during each minute of
      the 6MWT. An SPA index was created by subtracting the initial bodily discomfort
      ratings from the peak ratings. Results: Repeated-measures analysis of variance
      indicated that bodily discomfort significantly increased across the walking task,
      with approximately 60% of the sample experiencing SPA. Hierarchical regressions
      indicated that greater SPA was associated with fewer average steps per day and
      greater activity-related pain. Additionally, analyses revealed that temporal
      summation of pain and pain-related fear of movement significantly predicted the
      degree of SPA on the walking task. Conclusions: These findings shed light on
      potential mechanisms underlying SPA in older adults and suggest that SPA might be
      a risk factor for reduced physical activity.

PMID- 29036333
TI  - Analysis of primary microRNA loci from nascent transcriptomes reveals regulatory
      domains governed by chromatin architecture.

PMID- 29036335
TI  - Period effects in the risk of subsequent labour market marginalisation in young
      suicide attempters.
AB  - Background: Suicide attempt in young age is associated with subsequent labour
      market marginalisation, but little is known about how marginalisation is affected
      by changes in suicide attempt rates and social insurance legislation and by age
      differences. Methods: Prospective cohort study based on register linkage of > 2.4
      million Swedish residents per birth cohort, aged 19-40 years in 1999; 2004 and
      2009, respectively, and followed up for 4 years. Suicide attempters treated in
      inpatient care in the three years preceding study entry (n > 7000 per cohort)
      were compared with the general population of the same age without attempt (1987
      to end of follow-up). Hazard ratios (HR) and 95% confidence intervals for long
      term unemployment (>180 days), sickness absence (>90 days) and disability pension
      were calculated with Cox regression, adjusted for several risk markers.
      Additional analyses were stratified by age (below/above 30 years). Results:
      Across all cohorts, suicide attempt was associated with subsequent labour market
      marginalisation. Estimates were generally highest for disability pension [e.g.
      2009 cohort: adjusted (a) HR = 2.7], followed by sickness absence (2009 cohort:
      aHR = 2.3) and unemployment (2009 cohort: aHR = 1.5). aHRs were higher in the
      2004 and 2009 cohorts compared with the 1999 cohort. For disability pension, for
      example, aHRs were 2.39, 3.90 and 2.68 for the 1999, 2004 and 2009 cohorts,
      respectively. Stratification revealed marginal age differences. Conclusion: It
      seems to have become more difficult for suicide attempters to establish
      themselves on the labour market in later cohorts, which might result from changes
      in social insurance regulations. There were no considerable age differences.

PMID- 29036334
TI  - Tet1 facilitates hypoxia tolerance by stabilizing the HIF-alpha proteins
      independent of its methylcytosine dioxygenase activity.
AB  - Because of the requirement of oxygen (O2) to produce energy, aerobic organisms
      developed mechanisms to protect themselves against a shortage of oxygen in both
      acute status and chronic status. To date, how organisms tolerate acute hypoxia
      and the underlying mechanisms remain largely unknown. Here, we identify that
      Tet1, one member of the ten-eleven translocation (TET) family of methylcytosine
      dioxygenases, is required for hypoxia tolerance in zebrafish and mice. Tet1-null
      zebrafish and mice are more sensitive to hypoxic conditions compared with their
      wild-type siblings. We demonstrate that Tet1 stabilizes hypoxia-inducible factor
      alpha (HIF-alpha) and enhances HIF-alpha transcription activity independent of
      its enzymatic activity. In addition, we show that Tet1 modulates HIF-2alpha and
      HIF-1alpha through different mechanisms. Tet1 competes with prolyl hydroxylase
      protein 2 (PHD2) to bind to HIF-2alpha, resulting in a reduction of HIF-2alpha
      hydroxylation by PHD2. For HIF-1alpha, however, Tet1 has no effect on HIF-1alpha
      hydroxylation, but rather it appears to stabilize the C-terminus of HIF-1alpha by
      affecting lysine site modification. Furthermore, we found that Tet1 enhances
      rather than prevents poly-ubiquitination on HIF-alpha. Our results reveal a
      previously unrecognized function of Tet1 independent of its methylcytosine
      dioxygenase activity in hypoxia signaling.

PMID- 29036336
TI  - Missed Opportunities for Human Papillomavirus Vaccine Initiation in an Insured
      Adolescent Female Population.
AB  - Background: This study assessed the initiation of HPV vaccination in insured
      adolescent females in relation to physician visits and receipt of other vaccines
      routinely given at the same age. Methods: January 1, 2010, and September 31,
      2015. Vaccination administration was determined by using Current Procedural
      Terminology codes. A missed opportunity was defined as the absence of an HPV
      vaccine at the following encounter types: visits with a 4-valent meningococcal
      conjugate vaccine (MenACWY) or tetanus, diphtheria, and acellular pertussis
      (Tdap) vaccine claim; well adolescent visits; or any encounter with a primary
      care provider (PCP). Missed opportunities were stratified by type of provider
      (pediatrician or nonpediatrician). Results: Among 14588 adolescent girls, only
      6098 (41.8%) initiated the HPV vaccine series. HPV vaccine was given at 37.1% of
      visits when a Tdap or MenACWY vaccine was administered, 26.0% of well adolescent
      visits and 41.8% of PCP visits. Pediatricians had fewer missed opportunities than
      nonpediatricians to administer HPV (50.7% vs 60.8%), as well as Tdap, although
      the difference was larger for Tdap (7.0% vs 29.6%). Conclusions: These data
      indicate that pediatricians and nonpediatricians alike are missing opportunities
      to administer the HPV vaccine when other adolescent vaccines are given. Efforts
      should be focused on converting these missed vaccination opportunities into
      cancer-prevention visits.

PMID- 29036337
TI  - A Collection of Mutants for CLE-Peptide-Encoding Genes in Arabidopsis Generated
      by CRISPR/Cas9-Mediated Gene Targeting.
AB  - The ligand-receptor-mediated intercellular communication system plays important
      roles in coordinating developmental and physiological events in multicellular
      organisms. In plants, CLAVATA3/EMBRYO SURROUNDING REGION (CLE) peptides and their
      cognate receptors are thought to be involved in various aspects of the plant life
      cycle. Although the importance of this communication is broadly recognized, most
      CLE peptides are yet to be functionally characterized. A major problem in
      research on small signaling peptide-encoding genes is the limited number of loss
      of-function mutants available due to their small gene size. CRISPR/Cas9-mediated
      gene targeting has the potential to overcome this problem, as it can be used to
      generate targeted mutations in essentially any gene, regardless of size. Here we
      generated a series of mutants of CLE-peptide-encoding genes. Newly generated clv3
      and cle40 mutants reproduced the expected mutant phenotypes in the shoot apical
      meristem and root meristem, respectively. Our results show that CRISPR/Cas9
      mediated gene targeting is a powerful tool for genetic analyses, even of small
      genes. We also report a novel mutant for CLE44 [which is thought to encode a
      tracheary elements differentiation inhibitory factor (TDIF)] and show that CLE44
      contributes to vascular development. The bioresources presented here will be a
      powerful tool for further characterization of CLE peptides.

PMID- 29036338
TI  - High prevalence of arrhythmic and myocardial complications in patients with
      cardiac glycogenosis due to PRKAG2 mutations: Authors' reply.

PMID- 29036339
TI  - Contribution of major FLM isoforms to temperature-dependent flowering in
      Arabidopsis thaliana.
AB  - FLOWERING LOCUS M (FLM), a component of the thermosensory flowering time pathway
      in Arabidopsis thaliana, is regulated by temperature-dependent alternative
      splicing (AS). The main splicing variant, FLM-beta, is a well-documented floral
      repressor that is down-regulated in response to increasing ambient growth
      temperature. Two hypotheses have been formulated to explain how flowering time is
      modulated by AS of FLM. In the first model a second splice variant, FLM-delta,
      acts as a dominant negative isoform that competes with FLM-beta at elevated
      ambient temperatures, thereby indirectly promoting flowering. Alternatively, it
      has been suggested that the induction of flowering at elevated temperatures is
      caused only by reduced FLM-beta expression. To better understand the role of the
      two FLM splice forms, we employed CRISPR/Cas9 technology to specifically delete
      the exons that characterize each splice variant. Lines that produced repressive
      FLM-beta but were incapable of producing FLM-delta were late flowering. In
      contrast, FLM-beta knockout lines that still produced FLM-delta flowered early,
      but not earlier than the flm-3 loss of function mutant, as would be expected if
      FLM-delta had a dominant-negative effect on flowering. Our data support the role
      of FLM-beta as a flower repressor and provide evidence that a contribution of FLM
      delta to the regulation of flowering time in wild-type A. thaliana seems
      unlikely.

PMID- 29036341
TI  - Nothing in Biology Makes Sense But in the Light of Redox Regulation.

PMID- 29036340
TI  - 226Ra, 222Rn AND PERMEABILITY OF BELGIAN SOILS IN RELATION WITH INDOOR RADON
      RISK.
AB  - Knowing the concentration of 226Ra in soil and of 222Rn in soil gas is important
      for the analysis of indoor radon data and the prediction of radon-prone areas.
      Except for soil Rn in Ardenne, the data concerning these two radionuclides in
      Belgian soils are very scarce. In the context of Master theses and international
      courses, students made 92 measurements of 226Ra in soil samples, 105 of 222Rn in
      soil gas, and 74 of soil permeability, a significant addition to the existing
      similar data. The data are analysed in relation with soil texture, geological
      units and indoor radon risk. There is no clear correlation between radium in soil
      and indoor radon risk, the most important factor of risk being soil permeability.

PMID- 29036342
TI  - The ecophysiology of leaf cuticular transpiration: are cuticular water
      permeabilities adapted to ecological conditions?
AB  - When the stomata are closed under drought, the only route for water loss from the
      leaf interior to the atmosphere is across the cuticle. Thus, the extent of
      cuticular transpiration in relation to the reservoirs of water in the plant and
      the water acquisition from the soil determines the fitness and survival of the
      plant. It is, therefore, widely assumed that the cuticular water permeability of
      plants regularly experiencing drought is comparatively low and, thus, adapted to
      the environment. To test this hypothesis, 382 measurements of cuticular
      permeability from 160 species were extracted from the literature published
      between 1996 and 2017. The data had been produced either by using isolated
      cuticles and astomatous leaf sides or by measuring the minimum leaf conductance
      under conditions assumed to induce maximum stomatal closure. The species were
      assigned to 11 life form groups. Except for two particular cases (epiphytes, and
      climbers and lianas), the cuticular permeabilities of all groups either did not
      differ significantly or the available data did not allow a statistical test. In
      conclusion, present knowledge either does not support the hypothesis that
      ecological adaptions of cuticular water permeability exist or the available data
      are insufficient to test it.

PMID- 29036344
TI  - Comparison of the in vivo induction and transmission of alpha-synuclein pathology
      by mutant alpha-synuclein fibril seeds in transgenic mice.
AB  - Parkinson's disease (PD) is one of many neurodegenerative diseases termed
      synucleinopathies, neuropathologically defined by inclusions containing
      aggregated alpha-synuclein (alphaS). alphaS gene (SNCA) mutations can directly
      cause autosomal dominant PD. In vitro studies demonstrated that SNCA missense
      mutations may either enhance or diminish alphaS aggregation but cross-seeding of
      mutant and wild-type alphaS proteins appear to reduce aggregation efficiency.
      Here, we extended these studies by assessing the effects of seeded alphaS
      aggregation in alphaS transgenic mice through intracerebral or peripheral
      injection of various mutant alphaS fibrils. We observed modestly decreased time
      to paralysis in mice transgenic for human A53T alphaS (line M83) intramuscularly
      injected with H50Q, G51D or A53E alphaS fibrils relative to wild-type alphaS
      fibrils. Conversely, E46K alphaS fibril seeding was significantly delayed and
      less efficient in the same experimental paradigm. However, the amount and
      distribution of alphaS inclusions in the central nervous system were similar for
      all alphaS fibril muscle injected mice that developed paralysis. Mice transgenic
      for human alphaS (line M20) injected in the hippocampus with wild-type, H50Q,
      G51D or A53E alphaS fibrils displayed induction of alphaS inclusion pathology
      that increased and spread over time. By comparison, induction of alphaS
      aggregation following the intrahippocampal injection of E46K alphaS fibrils in
      M20 mice was much less efficient. These findings show that H50Q, G51D or A53E can
      efficiently cross-seed and induce alphaS pathology in vivo. In contrast, E46K
      alphaS fibrils are intrinsically inefficient at seeding alphaS inclusion
      pathology. Consistent with previous in vitro studies, E46K alphaS polymers are
      likely distinct aggregated conformers that may represent a unique prion-like
      strain of alphaS.

PMID- 29036345
TI  - Phase II study of cabozantinib in patients with progressive glioblastoma: subset
      analysis of patients with prior antiangiogenic therapy.
AB  - Background: Cabozantinib is a potent, multitarget inhibitor of MET and vascular
      endothelial growth factor receptor 2 (VEGFR2). This open-label, phase II trial
      evaluated cabozantinib in patients with recurrent or progressive glioblastoma
      (GBM). Methods: Patients were initially enrolled to a starting cabozantinib dose
      of 140 mg/day, but the starting dose was amended to 100 mg/day because of safety
      concerns. Treatment continued until disease progression or unacceptable toxicity.
      The primary endpoint was objective response rate, assessed by an independent
      radiology facility using modified Response Assessment in Neuro-Oncology criteria.
      Additional endpoints included duration of response, 6-month and median
      progression-free survival, overall survival, glucocorticoid use, and safety.
      Results: Among 222 patients enrolled, 70 had received prior antiangiogenic
      therapy. Herein, we report results in this subset of 70 patients. The objective
      response rate was 4.3%, and the median duration of response was 4.2 months. The
      proportion of patients alive and progression free at 6 months was 8.5%. Median
      progression-free survival was 2.3 months, and median overall survival was 4.6
      months. The most common adverse events reported in all patients, regardless of
      dose group, included fatigue (74.3%), diarrhea (47.1%), increased alanine
      aminotransferase (37.1%), headache (35.7%), hypertension (35.7%), and nausea
      (35.7%); overall, 34 (48.6%) patients experienced adverse events that resulted in
      dose reductions. Conclusions: Cabozantinib treatment appeared to have modest
      clinical activity with a 4.3% response rate in patients who had received prior
      antiangiogenic therapy for GBM. Clinical Trials Registration Number: NCT00704288
      (https://www.clinicaltrials.gov/ct2/show/NCT00704288).

PMID- 29036347
TI  - SIGNAL DECOMPOSITION AND ANALYSIS FOR THE IDENTIFICATION OF PERIODIC AND
      ANOMALOUS PHENOMENA IN RADON TIME-SERIES.
AB  - This work concerns continuous monitoring of radon and thoron specific activity in
      soil gas within the framework of identifying possible anomalies. It is based on
      the analysis of a medium-term data record obtained from soil gas in an area of
      geophysical interest. The RaMonA spectrometric system is also used to measure the
      climatic parameters and a specific analysis of the alpha spectra is performed to
      better determine the alpha lines intensity. Since radon emission is also
      influenced by meteorological parameters, it is mandatory to differentiate the
      changes due to the deep phenomena. Different procedures are utilized to reach the
      above objective: statistical analysis using the Empirical Mode Decomposition
      technique, the Multiple Linear Regression method and the Remote Radon Estimation
      by using of the thoron trend to eliminate the locally produced radon fraction.
      The results of such methods are compared to recognize and to highlight radon
      anomalies.

PMID- 29036348
TI  - CHARACTERISATION OF THE GRAPHITE MODERATED THERMAL NEUTRON FIELD AT CMI.
AB  - The graphite pile was set up at CMI to provide reference thermal neutron field
      for metrology and dosimetry purposes. It consists of three Pu-Be and three Am-Be
      radionuclide sources located in a 1.95 m (width) * 1.95 m (length) * 2.0 m
      (height) graphite moderator block. The neutron field in the volume of the
      experimental channel with dimensions of 40 cm * 40 cm * 135 cm (depth) was
      characterised experimentally and by Monte-Carlo calculations. Neutron fluence was
      determined by the activation of gold foils and Manganese tablets irradiated in
      nine different positions and by two 3He detectors of different construction
      irradiated in one position (bare and covered in three spherical PE moderators of
      3, 3.5 and 4 inch diameter). Weighted mean value of the neutron fluence rate
      measured by all the abovementioned detectors in the pile centre was 2.91 * 104 cm
      2 s-1 +/- 1.8%. This value was used as a calibration factor for the Monte-Carlo
      model predictions. The neutron spectral fluence rate calculated by validated
      Monte-Carlo model was used to determine the conventionally true ambient and
      personal dose equivalent rates at different positions.

PMID- 29036346
TI  - Opbp is a new architectural/insulator protein required for ribosomal gene
      expression.
AB  - A special class of poorly characterized architectural proteins is required for
      chromatin topology and enhancer-promoter interactions. Here, we identify Opbp as
      a new Drosophila architectural protein, interacting with CP190 both in vivo and
      in vitro. Opbp binds to a very restrictive set of genomic regions, through a rare
      sequence specific motif. These sites are co-bound by CP190 in vivo, and generally
      located at bidirectional promoters of ribosomal protein genes. We show that Opbp
      is essential for viability, and loss of opbp function, or destruction of its
      motif, leads to reduced ribosomal protein gene expression, indicating a
      functional role in promoter activation. As characteristic of
      architectural/insulator proteins, the Opbp motif is sufficient for distance
      dependent reporter gene activation and enhancer-blocking activity, suggesting an
      Opbp-mediated enhancer-promoter interaction. Rather than having a constitutive
      role, Opbp represents a new type of architectural protein with a very restricted,
      yet essential, function in regulation of housekeeping gene expression.

PMID- 29036349
TI  - Seasonal variations as predictive factors of the comet assay parameters: a
      retrospective study.
AB  - Since there are several predicting factors associated with the comet assay
      parameters, we have decided to assess the impact of seasonal variations on the
      comet assay results. A total of 162 volunteers were retrospectively studied,
      based on the date when blood donations were made. The groups (winter, spring,
      summer and autumn) were matched in terms of age, gender, smoking status, body
      mass index and medical diagnostic exposure in order to minimise the impact of
      other possible predictors. Means and medians of the comet assay parameters were
      higher when blood was sampled in the warmer period of the year, the values of
      parameters being the highest during summer. Correlation of meteorological data
      (air temperature, sun radiation and sun insolation) was observed when data were
      presented as the median per person. Using multivariate analysis, sampling season
      and exposure to medical radiation were proved to be the most influential
      predictors for the comet assay parameters. Taken together, seasonal variation is
      another variable that needs to be accounted for when conducting a cohort study.
      Further studies are needed in order to improve the statistical power of the
      results related to the impact of sun radiation, air temperature and sun
      insolation on the comet assay parameters.

PMID- 29036350
TI  - Prevalence of Hypertension Defined by Central Blood Pressure Measured Using a
      Type II Device in a Nationally Representative Cohort.
AB  - OBJECTIVES: Central blood pressure (BP) can be used to define hypertension. A
      central BP approach may be more sensitive than a conventional brachial BP
      approach in detecting hypertension. We aimed to compare the 2 approaches in
      estimating the prevalence hypertension in a nationally representative population.
      METHODS: A total of 2,742 adults older than 19 years participated in the 2013
      2016 National Nutrition and Health Survey in Taiwan. Central and brachial BP were
      simultaneously measured using a cuff-based stand-alone central BP monitor
      purporting to measure invasive central BP (type II device). Central hypertension
      was defined by central systolic (SBP)/diastolic BP (DBP) >=130 or 90 mm Hg or
      using antihypertensive medications, and brachial hypertension was defined by
      brachial SBP/DBP >=140 or 90 mm Hg or using antihypertensive medications.
      RESULTS: The World Health Organization-standardized and national weighted
      prevalence rates of central hypertension were 27.95% and 32.48%, respectively,
      and both were significantly higher than those of brachial hypertension (20.80%
      and 25.43%, both P < 0.001). The national weighted prevalence rates of concordant
      central and brachial hypertension, concordant central and brachial
      nonhypertension, isolated central hypertension, and isolated brachial
      hypertension were 25.13%, 67.22%, 7.35%, and 0.30%, respectively. Most subjects
      with the isolated central hypertension (97%) were within the range of brachial
      prehypertension, but only 38.0% of subject with brachial prehypertension had
      central hypertension. CONCLUSION: Almost one-third of a nationally representative
      population had hypertension detected by a central BP approach. Hypertension
      detection using a conventional brachial BP approach may underestimate the
      prevalence of hypertension and result in a less effective hypertension control.

PMID- 29036351
TI  - miRandola 2017: a curated knowledge base of non-invasive biomarkers.
AB  - miRandola (http://mirandola.iit.cnr.it/) is a database of extracellular non
      coding RNAs (ncRNAs) that was initially published in 2012, foreseeing the
      relevance of ncRNAs as non-invasive biomarkers. An increasing amount of
      experimental evidence shows that ncRNAs are frequently dysregulated in diseases.
      Further, ncRNAs have been discovered in different extracellular forms, such as
      exosomes, which circulate in human body fluids. Thus, miRandola 2017 is an effort
      to update and collect the accumulating information on extracellular ncRNAs that
      is spread across scientific publications and different databases. Data are
      manually curated from 314 articles that describe miRNAs, long non-coding RNAs and
      circular RNAs. Fourteen organisms are now included in the database, and
      associations of ncRNAs with 25 drugs, 47 sample types and 197 diseases. miRandola
      also classifies extracellular RNAs based on their extracellular form: Argonaute2
      protein, exosome, microvesicle, microparticle, membrane vesicle, high density
      lipoprotein and circulating. We also implemented a new web interface to improve
      the user experience.

PMID- 29036352
TI  - Environmental Plasticity in the Intersexual Correlation and Sex Bias of Gene
      Expression.
AB  - Intersexual genetic correlations are expected to constrain the evolution of
      sexual dimorphic traits, including the degree of sex-biased gene expression.
      Consistent with that expectation, studies in fruit flies and birds have reported
      that genes whose expression has a strong intersexual genetic correlation (rMF)
      show a lower level of sex-biased expression (SBE). However, it is known that both
      rMF and SBE can be affected by the environment. It is therefore unclear whether
      there is a consistent relationship between these 2 quantities across multiple
      environments. In this paper, we study this relationship in the African malaria
      mosquito Anopheles gambiae. We show that both rMF and SBE change between
      environments. The change in SBE across environments is significantly correlated
      with dN/dS: greater changes in SBE are associated with higher values of dN/dS.
      Furthermore, the relationship between rMF and SBE is sensitive to the
      environment. We conclude that this relationship is sufficiently plastic that
      environmental effects should be considered in future studies.

PMID- 29036353
TI  - Structural insights into RNA unwinding and degradation by RNase R.
AB  - RNase R is a conserved exoribonuclease in the RNase II family that primarily
      participates in RNA decay in all kingdoms of life. RNase R degrades duplex RNA
      with a 3' overhang, suggesting that it has RNA unwinding activity in addition to
      its 3'-to-5' exoribonuclease activity. However, how RNase R coordinates RNA
      binding with unwinding to degrade RNA remains elusive. Here, we report the
      crystal structure of a truncated form of Escherichia coli RNase R (residues 87
      725) at a resolution of 1.85 A. Structural comparisons with other RNase II family
      proteins reveal two open RNA-binding channels in RNase R and suggest a tri-helix
      'wedge' region in the RNB domain that may induce RNA unwinding. We constructed
      two tri-helix wedge mutants and they indeed lost their RNA unwinding but not RNA
      binding or degrading activities. Our results suggest that the duplex RNA with an
      overhang is bound in the two RNA-binding channels in RNase R. The 3' overhang is
      threaded into the active site and the duplex RNA is unwound upon reaching the
      wedge region during RNA degradation. Thus, RNase R is a proficient enzyme,
      capable of concurrently binding, unwinding and degrading structured RNA in a
      highly processive manner during RNA decay.

PMID- 29036354
TI  - PLncPRO for prediction of long non-coding RNAs (lncRNAs) in plants and its
      application for discovery of abiotic stress-responsive lncRNAs in rice and
      chickpea.
AB  - Long non-coding RNAs (lncRNAs) make up a significant portion of non-coding RNAs
      and are involved in a variety of biological processes. Accurate
      identification/annotation of lncRNAs is the primary step for gaining deeper
      insights into their functions. In this study, we report a novel tool, PLncPRO,
      for prediction of lncRNAs in plants using transcriptome data. PLncPRO is based on
      machine learning and uses random forest algorithm to classify coding and long non
      coding transcripts. PLncPRO has better prediction accuracy as compared to other
      existing tools and is particularly well-suited for plants. We developed consensus
      models for dicots and monocots to facilitate prediction of lncRNAs in non
      model/orphan plants. The performance of PLncPRO was quite better with vertebrate
      transcriptome data as well. Using PLncPRO, we discovered 3714 and 3457 high
      confidence lncRNAs in rice and chickpea, respectively, under drought or salinity
      stress conditions. We investigated different characteristics and differential
      expression under drought/salinity stress conditions, and validated lncRNAs via RT
      qPCR. Overall, we developed a new tool for the prediction of lncRNAs in plants
      and showed its utility via identification of lncRNAs in rice and chickpea.

PMID- 29036356
TI  - Lipopolysaccharide promotes angiogenesis in mice model of HCC by stimulating
      hepatic stellate cell activation via TLR4 pathway.
AB  - Angiogenesis plays a key role in the progression of hepatocellular carcinoma
      (HCC). This study aimed to investigate whether lipopolysaccharide (LPS) could
      promote HCC angiogenesis and the role of hepatic stellate cell (HSC) in this
      process. In vivo orthotopic HCC model and the effect of LPS on HSC in vitro were
      studied. Our results demonstrated that LPS-induced HSC activation during the
      promotion of HCC growth and angiogenesis in mice. The LPS-TLR4 (Toll-like
      receptor 4) pathway in HSC is responsible for HCC angiogenesis. LPS-induced
      secretion of pro-angiogenic factors from HSC could promote endothelial cell
      migration and tubulogenesis. This study suggests that LPS acts with HSC in tumor
      stroma and promotes the secretion of pro-angiogenic factors that increase
      angiogenesis in HCC.

PMID- 29036355
TI  - Design and implementation of a synthetic pre-miR switch for controlling miRNA
      biogenesis in mammals.
AB  - Synthetic RNA-based systems have increasingly been used for the regulation of
      eukaryotic gene expression. Due to their structural properties, riboregulators
      provide a convenient basis for the development of ligand-dependent controllable
      systems. Here, we demonstrate reversible conditional control of miRNA biogenesis
      with an aptamer domain as a sensing unit connected to a natural miRNA precursor
      for the first time. For the design of the pre-miR switch, we replaced the natural
      terminal loop with the TetR aptamer. Thus, the TetR aptamer was positioned close
      to the Dicer cleavage sites, which allowed sterical control over pre-miR
      processing by Dicer. Our design proved to be highly versatile, allowing us to
      regulate the biogenesis of three structurally different miRNAs: miR-126, -34a and
      -199a. Dicer cleavage was inhibited up to 143-fold via co-expression of the TetR
      protein, yet could be completely restored upon addition of doxycycline. Moreover,
      we showed the functionality of the pre-miR switches for gene regulation through
      the interaction of the respective miRNA with its specific target sequence. Our
      designed device is capable of robust and reversible control of miRNA abundance.
      Thus, we offer a novel investigational tool for functional miRNA analysis.

PMID- 29036357
TI  - Chronic magnesium deficiency and human disease; time for reappraisal?
AB  - Numerous epidemiological, experimental and clinical studies over the last 30
      years have consistently shown that chronic magnesium deficiency is associated
      with and/or exacerbates a number of major disorders (Table 1). Yet chronic
      magnesium deficiency is not widely recognized and a major reason for this failure
      is that serum magnesium levels do not accurately reflect body magnesium stores.
      Specifically, in chronic magnesium deficiency, serum magnesium levels are often
      within the normal reference range (usually lowest quartile) and may not progress
      to overt hypomagnesaemia. This raises serious questions namely (i) should chronic
      magnesium deficiency be considered in high-risk patients irrespective of serum
      magnesium, even when 'normal'? and (ii) if recognized, should oral magnesium
      supplement be given to restore body stores? Appreciating the vital role of
      magnesium for normal cellular function and bone health may help in formulating a
      well-considered and justifiable approach to these questions. Pragmatic tests for
      assessing magnesium status in the adult are suggested and discussed.

PMID- 29036359
TI  - proFIA: a data preprocessing workflow for flow injection analysis coupled to high
      resolution mass spectrometry.
AB  - Motivation: Flow Injection Analysis coupled to High-Resolution Mass Spectrometry
      (FIA-HRMS) is a promising approach for high-throughput metabolomics. FIA-HRMS
      data, however, cannot be preprocessed with current software tools which rely on
      liquid chromatography separation, or handle low resolution data only. Results: We
      thus developed the proFIA package, which implements a suite of innovative
      algorithms to preprocess FIA-HRMS raw files, and generates the table of peak
      intensities. The workflow consists of 3 steps: (i) noise estimation, peak
      detection and quantification, (ii) peak grouping across samples and (iii) missing
      value imputation. In addition, we have implemented a new indicator to quantify
      the potential alteration of the feature peak shape due to matrix effect. The
      preprocessing is fast (less than 15 s per file), and the value of the main
      parameters (ppm and dmz) can be easily inferred from the mass resolution of the
      instrument. Application to two metabolomics datasets (including spiked serum
      samples) showed high precision (96%) and recall (98%) compared with manual
      integration. These results demonstrate that proFIA achieves very efficient and
      robust detection and quantification of FIA-HRMS data, and opens new opportunities
      for high-throughput phenotyping. Availability and implementation: The proFIA
      software (as well as the plasFIA dataset) is available as an R package on the
      Bioconductor repository (http://bioconductor.org/packages/proFIA), and as a
      Galaxy module on the Main Toolshed (https://toolshed.g2.bx.psu.edu), and on the
      Workflow4Metabolomics online infrastructure (http://workflow4metabolomics.org).
      Contact: alexis.delabriere@cea.fr or etienne.thevenot@cea.fr. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29036358
TI  - Divergent effects of oxytocin on (para-)limbic reactivity to emotional and
      neutral scenes in females with and without borderline personality disorder.
AB  - Borderline personality disorder (BPD) patients' hypersensitivity for emotionally
      relevant stimuli has been suggested be due to abnormal activity and connectivity
      in (para-)limbic and prefrontal brain regions during stimulus processing. The
      neuropeptide oxytocin has been shown to modulate activity and functional
      connectivity in these brain regions, thereby optimizing the processing of
      emotional and neutral stimuli. To investigate whether oxytocin would be capable
      of attenuating BPD patients' hypersensitivity for such stimuli, we recorded brain
      activity and gaze behavior during the processing of complex scenes in 51 females
      with and 48 without BPD after intranasal application of either oxytocin or
      placebo. We found divergent effects of oxytocin on BPD and healthy control (HC)
      participants' (para-)limbic reactivity to emotional and neutral scenes: Oxytocin
      decreased amygdala and insula reactivity in BPD participants but increased it in
      HC participants, indicating an oxytocin-induced normalization of amygdala and
      insula activity during scene processing. In addition, oxytocin normalized the
      abnormal coupling between amygdala activity and gaze behavior across all scenes
      in BPD participants. Overall, these findings suggest that oxytocin may be capable
      of attenuating BPD patients' hypersensitivity for complex scenes, irrespective of
      their valence.

PMID- 29036360
TI  - Subcellular localization and interactions among rubber particle proteins from
      Hevea brasiliensis.
AB  - Natural rubber (polyisoprene) from the rubber tree Hevea brasiliensis is
      synthesized by specialized cells called laticifers. It is not clear how rubber
      particles arise, although one hypothesis is that they derive from the endoplasmic
      reticulum (ER) membrane. Here we cloned the genes encoding four key proteins
      found in association with rubber particles and studied their intracellular
      localization by transient expression in Nicotiana benthamiana leaves. We show
      that, while the cis-prenyltransferase (CPT), responsible for the synthesis of
      long polyisoprene chains, is a soluble, cytosolic protein, other rubber particle
      proteins such as rubber elongation factor (REF), small rubber particle protein
      (SRPP) and Hevea rubber transferase 1-REF bridging protein (HRBP) are associated
      with the endoplasmic reticulum (ER). We also show that SRPP can recruit CPT to
      the ER and that interaction of CPT with HRBP leads to both proteins relocating to
      the plasma membrane. We discuss these results in the context of the biogenesis of
      rubber particles.

PMID- 29036361
TI  - Chronic Pain and Neuropathy Following Adjuvant Chemotherapy.
AB  - Objective: To determine symptoms and characteristics of chronic sensory
      neuropathy in patients treated with oxaliplatin and docetaxel, including patterns
      of somatosensory abnormalities, pain descriptors, and psychological functioning.
      Design: A retrospective cross-sectional study. Setting: A chronic pain research
      center. Subjects: Thirty-eight patients with chronic peripheral pain and/or
      dysesthesia following chemotherapy. Methods: Sensory profiles, psychological
      functioning, and quality of life were assessed using standardized questionnaires.
      In addition, standardized quantitative sensory testing and nerve conduction
      studies were carried out. Results: The sensory profiles and clinical symptoms
      were very similar in the two groups. Pricking, numbness, and burning were common
      descriptors in both groups, and the predominant finding was sensory loss to A
      beta-mediated sensory modalities with decreased mechanical and vibration
      detection thresholds. A high frequency of abnormalities in thermal sensory limen
      and the presence of paradoxical heat sensation seem to be sensitive markers of
      small fiber loss. Both groups had mainly sensory, axonal large fiber or mixed
      fiber polyneuropathy, which tended to be most severe in the oxaliplatin group.
      Conclusions: Both oxaliplatin-induced and docetaxel-induced polyneuropathies
      represent a significant problem that affects the daily life of the patients. Our
      results, defining the somatosensory phenotype, can improve the understanding of
      the pathophysiological mechanisms useful for future studies in the tailored
      treatment of prevention of chemotherapy-induced peripheral neuropathy and pain.

PMID- 29036362
TI  - CUX1 stimulates APE1 enzymatic activity and increases the resistance of
      glioblastoma cells to the mono-alkylating agent temozolomide.
AB  - Background: Cut Like homeobox 1 (CUX1), which encodes an auxiliary factor in base
      excision repair, resides on 7q22.1, the most frequently and highly amplified
      chromosomal region in glioblastomas. The resistance of glioblastoma cells to the
      mono-alkylating agent temozolomide is determined to some extent by the activity
      of apurinic/apyrimidinic endonuclease 1 (APE1). Methods: To monitor the effect of
      CUX1 and its CUT domains on APE1 activity, DNA repair assays were performed with
      purified proteins and cell extracts. CUX1 protein expression was analyzed by
      immunohistochemistry using a tumor microarray of 150 glioblastoma samples. The
      effect of CUX1 knockdown and overexpression on the resistance of glioblastoma
      cell lines to temozolomide was investigated. Results: We show that CUT domains
      stimulate APE1 activity. In agreement with these findings, CUX1 knockdown causes
      an increase in the number of abasic sites in genomic DNA and a decrease in APE1
      activity as measured in cell extracts. Conversely, ectopic CUX1 expression
      increases APE1 activity and lowers the number of abasic sites. Having established
      that CUX1 is expressed at high levels in most glioblastomas, we next show that
      the resistance of glioblastoma cells to temozolomide and to a combined treatment
      of temozolomide and ionizing radiation is reduced following CUX1 knockdown, but
      increased by overexpression of CUX1 or a short protein containing only 2 CUT
      domains, which is active in DNA repair but devoid of transcriptional activity.
      Conclusion: These findings indicate that CUX1 expression level impacts on the
      response of glioblastoma cells to treatment and identifies the CUT domains as
      potential therapeutic targets.

PMID- 29036363
TI  - Predictive Ability of Intermittent Daily Sickle Cell Pain Assessment: The PiSCES
      Project.
AB  - Background: Pain diary assessment in sickle cell disease (SCD) may be expensive
      and impose a high respondent burden. Objective: To report whether intermittent
      assessment could substitute for continuous daily pain assessment in SCD. Design:
      Prospective cohort study. Setting: Academic and community practices in Virginia.
      Patients. A total of 125 SCD patients age 16 years or older in the Pain in Sickle
      Cell Epidemiology Study. Measurements. Using pain measures that summarized all
      diaries as the gold standard, we tested the statistical equivalence of four
      alternative strategies that summarized diaries only from the week prior or the
      month prior to study completion; one week per month; or one day per week (random
      day). Summary measures included percent pain days, percent crisis days (self
      defined), mean pain (0-9 Likert scale) on all days, and mean pain on pain days.
      Equivalence tests included comparisons of means, regression intercepts, and
      slopes, as well as measurement of R2. Results: Compared with the gold standard,
      the one-day-per-week and one-week-per-month strategies yielded statistically
      equivalent means of six summary pain measures, and the week prior and month prior
      yielded equivalent means as some of the measures. Regression showed statistically
      equivalent slopes and intercepts to the gold standard using one-day-per-week and
      one-week-per-month strategies for percent pain days and percent crisis days, but
      almost no other equivalence. R2 values ranged from 0.64 to 0.989. Conclusions: It
      is possible to simulate five- to six-month daily assessment of pain in SCD.
      Either one-day-per-week or one-week-per-month assessment yields an equivalent
      mean and fair regression equivalence.

PMID- 29036364
TI  - NANODOSIMETRY: TOWARDS A NEW CONCEPT OF RADIATION QUALITY.
AB  - The biological action of ionizing charged particles is initiated at the DNA
      level, and the effectiveness with which the initial physical effect changes into
      measurable biological damage is likely ruled by the stochastics of ionizations
      produced by the incident ions in subcellular nanometric volumes. Based on this
      hypothesis, experimental nanodosimetry aims at establishing a new concept of
      radiation quality that builds on measurable characteristics of the particle track
      structure at the nanometer scale. Three different nanodosimetric detection
      systems have been developed to date that allow measurements of the number of
      ionizations produced by the passage of a primary particle in a nanometer-size gas
      volume (in unit density scale). Within the Italian project MITRA (MIcrodosimetry
      and TRAck structure), funded by the Italian Istituto Nazionale di Fisica Nucleare
      (INFN) and the EMRP Joint Research Project 'BioQuaRT' (Biologically Weighted
      Quantities in Radiotherapy), experiments have been carried out, in which the
      frequency distribution of ionizations produced by proton and carbon ion beams of
      given energy was measured with the three nanodosimetric detectors. Descriptors of
      the track structure can be derived from these distributions. In particular, the
      first moment M1, representing the mean number of ionizations produced in the
      target volume, and the cumulative probability Fk of measuring a number nu >= k of
      ionizations. The correlation between measured nanodosimetric quantities and
      experimental radiobiological data available in the literature is here presented
      and discussed.

PMID- 29036365
TI  - The developmental origin and compartmentalization of glutathione-s-transferase
      omega 2 isoforms in the perinuclear theca of eutherian spermatozoa.
AB  - The perinuclear theca (PT) is a condensed, nonionic detergent resistant cytosolic
      protein layer encapsulating the sperm head nucleus. It can be divided into two
      regions: the subacrosomal layer, whose proteins are involved in acrosomal
      assembly during spermiogenesis, and the postacrosomal sheath (PAS), whose
      proteins are implicated in sperm-oocyte interactions during fertilization. In
      continuation of our proteomic analysis of the PT, we have isolated two prominent
      PT-derived proteins of 28 and 31 kDa from demembranated bovine sperm head
      fractions. These proteins were identified by mass spectrometry as isoforms of
      glutathione-s-transferase omega 2 (GSTO2). Immunoblots probed with anti-GSTO2
      antibodies confirmed the presence of the GSTO2 isoforms in these fractions while
      fluorescent immunocytochemistry localized the isoforms to the PAS region of the
      bull, boar, and murid PT. In addition to the PAS labeling of GSTO2, the
      performatorium of murid spermatozoa was also labeled. Immunohistochemistry of rat
      testes revealed that GSTO2 was expressed in the third phase of spermatogenesis
      (i.e., spermiogenesis) and assembled in the PAS and perforatorial regions of late
      elongating spermatids. Fluorescent immunocytochemistry performed on murine testis
      cells co-localized GSTO2 and tubulin on the transient microtubular-manchette of
      elongating spermatids. These findings imply that GSTO2 is transported and
      deposited in the PAS region by the manchette, conforming to the pattern of
      assembly found with other PAS proteins. The late assembly of GSTO2 and its
      localization in the PAS suggests a role in regulating the oxidative and reductive
      state of covalently linked spermatid/sperm proteins, especially during the
      disassembly of the sperm accessory structures after fertilization.

PMID- 29036366
TI  - Accounting for Selectivity Bias and Correlation Across the Sequence From Elevated
      Blood Pressure to Hypertension Diagnosis and Treatment.
AB  - BACKGROUND: It is unknown whether efforts to reduce hypertension burden in
      countries with very high prevalence, would be more effective if directed at
      hypertension diagnosis vs. treatment. Most analyses do not address bias and
      correlation across the sequence from elevated blood pressure (BP) to hypertension
      diagnosis and treatment, leading to potentially misleading findings. METHODS:
      Using data spanning 18 years of the China Health and Nutrition Survey (n =
      18,926; ages 18-75 years), we used an innovative 3-step, integrated system of
      equations to predict the sequence from: (i) elevated BP (systolic/diastolic BP >=
      140/90 mm Hg) to (ii) diagnosed hypertension conditional on elevated BP, and to
      (iii) treatment (medication use) conditional on diagnosis, accounting for
      measured and unmeasured individual- and community-level confounders at each of
      the 3 steps. We compared results to separate traditional logistic regression
      models without control for unmeasured confounding. RESULTS: Using our 3-step
      model, elevated BP increased from 12.6% and 8.5% (1991) to 36.8% and 29% (2009)
      in men and women, respectively, but diagnosis remained under 50%. We found
      widening disparities in hypertension diagnosis (higher hypertension at lower vs.
      higher education (difference of 2% in 1991 that widened to 5% in 2009)) and
      narrowing disparities in education (difference of 6% in 1991 to 4% in 2009) and
      insurance status (difference of 7% in 1991 to 2% in 2009) for treatment.
      CONCLUSIONS: Our 3-step model improved model fit over traditionally used models.
      Our findings highlight serious barriers to hypertension diagnosis in Chinese
      adults, particularly among men and individuals of low attained education.

PMID- 29036367
TI  - Phenylalanine as a nitrogen source induces root growth and nitrogen-use
      efficiency in Populus * canescens.
AB  - To investigate the physiological responses of poplars to amino acids as sole
      nitrogen (N) sources, Populus * canescens (Ait.) Smith plants were supplied with
      one of three nitrogen fertilizers (NH4NO3, phenylalanine (Phe) or the mixture of
      NH4NO3 and Phe) in sand culture. A larger root system, and decreased leaf size
      and CO2 assimilation rate was observed in Phe- versus NH4NO3-treated poplars.
      Consistently, a greater root biomass and a decreased shoot growth were detected
      in Phe-supplied poplars. Decreased enzymatic activities of nitrate reductase
      (NR), glutamate synthase (GOGAT) and glutamate dehydrogenase (GDH) and elevated
      activities of nitrite reductase (NiR), phenylalanine ammonia lyase (PAL),
      glutamine synthetase (GS) and asparagine synthase (AS) were found in Phe-treated
      roots. Accordingly, reduced concentrations of NH4+, NO3- and total N, and
      enhanced N-use efficiencies (NUEs) were detected in Phe-supplied poplars.
      Moreover, the transcript levels of putative Phe transporters ANT1 and ANT3 were
      upregulated, and the mRNA levels of NR, glutamine synthetase 2 (GS2), NADH
      dependent glutamate synthase (NADH-GOGAT), GDH and asparagine synthetase 2 (ASN2)
      were downexpressed in Phe-treated roots and/or leaves. The 15N-labeled Phe was
      mainly allocated in the roots and only a small amount of 15N-Phe was translocated
      to poplar aerial parts. These results indicate that poplar roots can acquire Phe
      as an N source to support plant growth and that Phe-induced NUEs in the poplars
      are probably associated with NH4+ re-utilization after Phe deamination and the
      carbon bonus simultaneously obtained during Phe uptake.

PMID- 29036369
TI  - Referral of patients with fever of unknown origin to an expertise center has high
      diagnostic and therapeutic value.
AB  - Background: up to 50% of patients with fever of unknown origin (FUO) remain
      undiagnosed despite extensive evaluation. In expertise centers, at least 25-63%
      of these patients is referred after evaluation in another hospital. The
      diagnostic and therapeutic yields of referral to an expertise center are
      currently unknown. Aim: To determine the diagnostic and therapeutic yield of
      referral of patients with fever of unknown origin (FUO) that remain undiagnosed
      in non-expertise hospitals. Design: Data on workup, outcome, treatment and
      prognosis were extracted from medical records of all 236 patients referred to the
      Radboud university medical center's department of internal medicine because of
      FUO between January 2005 and June 2014. Results: A final diagnosis could be made
      in 110 of 192 tertiary referred FUO patients. The rate of diagnosis did not
      differ between patients referred for first opinion or after tertiary referral
      (68.2 versus 57.3%, p=.234). Over half of undiagnosed tertiary referred patients
      were treated, and fever resolved in half of these patients. Of 96 undiagnosed
      patients, two died (2.1)% and in both death was considered unrelated to the
      febrile disease. Conclusion: The diagnostic rate in patients with FUO does not
      differ between patients that are tertiary referred and patients that have not
      been previously evaluated in another hospital. With a total diagnostic value of
      57.3% and an additional therapeutic yield of 10.9% in undiagnosed patients,
      tertiary referral should therefore be considered in patients that remain
      undiagnosed in a non-expertise center.

PMID- 29036370
TI  - Estimation of the effects of multipoint pacing on battery longevity in routine
      clinical practice.
AB  - Aims: Multipoint pacing (MPP) permits simultaneous multisite pacing of the left
      ventricle (LV); initial studies suggest haemodynamic and clinical benefits over
      conventional (single LV site) cardiac resynchronization therapy (CRT). The aim of
      this study was to estimate the impact of MPP activation on battery longevity in
      routine clinical practice. Methods and results: Patient (n = 46) and device data
      were collected from two centres at least 3 months after MPP-CRT device
      implantation. Multipoint pacing programming was based on the maximal possible
      anatomical LV1/LV2 separation according to three predefined LV pacing capture
      threshold (PCT) cut-offs (<=1.5 V; <=4.0 V; and <=6.5 V). Estimated battery
      longevity was calculated using the programmed lower rate limit, lead impedances,
      outputs, and pacing percentages. Relative to the longevity for conventional CRT
      using the lowest PCT (8.9 +/- 1.2 years), MPP activation significantly shortened
      battery longevity for all three PCT cut-offs (<=1.5 V, -5.6%; <=4.0 V, -16.9%;
      <=6.5 V, -21.3%; P's <0.001). When compared with conventional CRT based on
      longest right ventricle-LV delay (8.3 +/- 1.3 years), battery longevity was
      significantly shortened for the MPP <= 4.0 V and <=6.5 V cut-offs (-10.8 and 
      15.7%, respectively; P's <0.001). Maximal LV1/LV2 spacing was possible in 23.9%
      (<=1.5 V), 56.5% (<=4.0 V), and 69.6% (<=6.5 V) of patients. Conclusion:
      Multipoint pacing activation significantly reduces battery longevity compared
      with that for conventional CRT configuration. When reasonable MPP LV vector PCTs
      (<=4.0 V) are achieved, the decrease in battery longevity is relatively small
      which may prompt the clinician to activate MPP.

PMID- 29036368
TI  - Proteomic identification of histone post-translational modifications and proteins
      enriched at a DNA double-strand break.
AB  - Here, we use ChAP-MS (chromatin affinity purification with mass spectrometry),
      for the affinity purification of a sequence-specific single-copy endogenous
      chromosomal locus containing a DNA double-strand break (DSB). We found multiple
      new histone post-translational modifications enriched on chromatin bearing a DSB
      from budding yeast. One of these, methylation of histone H3 on lysine 125, has
      not previously been reported. Among over 100 novel proteins enriched at a DSB
      were the phosphatase Sit4, the RNA pol II degradation factor Def1, the mRNA
      export protein Yra1 and the HECT E3 ligase Tom1. Each of these proteins was
      required for resistance to radiomimetics, and many were required for resistance
      to heat, which we show here to cause a defect in DSB repair in yeast. Yra1 and
      Def1 were required for DSB repair per se, while Sit4 was required for rapid
      inactivation of the DNA damage checkpoint after DSB repair. Thus, our unbiased
      proteomics approach has led to the unexpected discovery of novel roles for these
      and other proteins in the DNA damage response.

PMID- 29036371
TI  - Additive Effect of Cigarette Smoking on Gray Matter Abnormalities in
      Schizophrenia.
AB  - It is widely known that there is a high prevalence of cigarette smoking in
      schizophrenia. One of the explanations is the self-medication hypothesis. Based
      on this hypothesis, it has been suggested that nicotine has procognitive effect
      or even neuroprotective effect in schizophrenia. However, cigarettes contain
      numerous neurotoxic substances, making the net effect of cigarette smoking on
      brain function and structure complex. Indeed, recent studies have called into
      question the self-medication hypothesis. We aimed to test whether there is an
      interaction between diagnosis and smoking status in gray matter volume, ie,
      whether smoking has specific effects on gray matter or whether main effects of
      these 2 variables additively affect common brain regions. Magnetic resonance
      imaging (MRI) images were obtained from 4 groups: (1) normal controls with no
      smoking history, (2) normal controls currently smoking and/or with a past history
      of smoking, (3) schizophrenia patients with no smoking history, and (4)
      schizophrenia patients currently smoking and/or with a past history of smoking.
      We used voxel-based morphometry to compare gray matter volumes among the 4
      groups. We did not find any interaction between diagnosis and smoking, but we did
      find negative additive effects of schizophrenia diagnosis and smoking status in
      the left prefrontal cortex. The decrease in left prefrontal volume was associated
      with greater numbers of cigarette pack years and severe positive and negative
      symptoms. The current findings do not support the neuroprotective effect of
      smoking on gross brain structure in schizophrenia, emphasizing the necessity of
      longitudinal studies to test causal relationships among these variables.

PMID- 29036372
TI  - SEARCH AND MAPPING OF THE OLD BURIED TAILINGS WITH RADIOACTIVE WASTES AT THE
      URBAN TERRITORY.
AB  - The article presents results of investigation on search and mapping of the old
      buried tailings with radioactive wastes on the territory of Kamianske City. For
      solving the problem used complex of methods. These methods are as follows: soil
      gas 222Rn measurement and measurement of 222Rn flux density from the ground
      surface, gamma-radiation survey, prospecting drilling, gamma-ray logging and
      laboratory analysis of radionuclides. The leading method in this complex was the
      method of soil-gas 222Rn measurement. Using this method location of the tailings
      has been precisely defined. The tailings boundaries have been contoured in the
      plan. Other methods permitted to define such parameters as thickness of the
      wastes, their volume (~330 000 m3), radionuclide and chemical composition. It was
      found that radioactive residues occur at a depth from 2 to 11 m and contain in
      its composition 226Ra, 210Pb and 210Po in the range from 8370 to 37 270 Bq kg-1.

PMID- 29036373
TI  - SUMMARY OF THE EIGHTH CONFERENCE ON PROTECTION AGAINST RADON AT HOME AND AT WORK
      AND THE 13TH WORKSHOP ON THE GEOLOGICAL ASPECTS OF RADON RISK MAPPING.
AB  - This paper provides summary of the 8th Conference on Protection against Radon at
      Home and at Work and 13th Workshop on the Geological Aspects of Radon Risk
      Mapping held in September 2016 in Prague, Czech Republic.

PMID- 29036374
TI  - Gating mass cytometry data by deep learning.
AB  - Motivation: Mass cytometry or CyTOF is an emerging technology for high
      dimensional multiparameter single cell analysis that overcomes many limitations
      of fluorescence-based flow cytometry. New methods for analyzing CyTOF data
      attempt to improve automation, scalability, performance and interpretation of
      data generated in large studies. Assigning individual cells into discrete groups
      of cell types (gating) involves time-consuming sequential manual steps, untenable
      for larger studies. Results: We introduce DeepCyTOF, a standardization approach
      for gating, based on deep learning techniques. DeepCyTOF requires labeled cells
      from only a single sample. It is based on domain adaptation principles and is a
      generalization of previous work that allows us to calibrate between a target
      distribution and a source distribution in an unsupervised manner. We show that
      DeepCyTOF is highly concordant (98%) with cell classification obtained by
      individual manual gating of each sample when applied to a collection of 16
      biological replicates of primary immune blood cells, even when measured across
      several instruments. Further, DeepCyTOF achieves very high accuracy on the semi
      automated gating challenge of the FlowCAP-I competition as well as two CyTOF
      datasets generated from primary immune blood cells: (i) 14 subjects with a
      history of infection with West Nile virus (WNV), (ii) 34 healthy subjects of
      different ages. We conclude that deep learning in general, and DeepCyTOF
      specifically, offers a powerful computational approach for semi-automated gating
      of CyTOF and flow cytometry data. Availability and implementation: Our codes and
      data are publicly available at https://github.com/KlugerLab/deepcytof.git.
      Contact: yuval.kluger@yale.edu. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29036375
TI  - URANIUM IN SOIL AND GAMMA DOSE RATE AS PROXIES FOR THE INDOOR RADON RISK:
      SITUATION IN BELGIUM.
AB  - Radon risk maps are usually based either on indoor radon data, or on measurements
      of soil gas radon and soil permeability. If these data are not available or not
      sufficient, it was suggested that other data could be used as an approximate
      substitute (a proxy) to the missing information, like the concentration of 238U
      or 226Ra in soils or the terrestrial gamma dose rate (TGDR). We examine here the
      correlation between airborne measurements of soil U and indoor radon, and between
      airborne U and TGDR, and their link with affected/unaffected areas. No clear
      correlation is found between airborne U and affected areas, as strongly affected
      areas are not characterised by a higher U level. Only the moderately affected
      area of Condroz can be connected to a higher U level, related to a few U
      anomalies. TGDR shows a rather good correlation with airborne U, but its relation
      with radon risk is less clear. Soil uranium and TGDR may help to screen out areas
      with very low U and very low TGDR, which have a low indoor radon risk, but they
      cannot be considered as good proxies for predicting radon-affected areas in
      Belgium.

PMID- 29036377
TI  - RADON CHAMBER IN THE CENTRAL MINING INSTITUTE-THE CALIBRATION FACILITY FOR RADON
      AND RADON PROGENY MONITORS.
AB  - The article presents the advantages of the radon chamber with volume of 17 m3,
      that belongs to Silesian Centre for Environmental Radioactivity and its
      applicability for calibration of equipment designed to measure the radon
      concentration and its short-lived decay products. The chamber can be operated
      under controlled conditions in the range from -20 to 60 degrees C and relative
      humidity from 20 to 90%. There is also discussed the influence of aerosol
      concentration and their size distribution on the calibration results. When
      calibrating the measuring devices in an atmosphere with a large contribution of
      ultrafine particles that are defined as particles with diameter <0.1 MUm, their
      sensitivity may decrease by tens of percent.

PMID- 29036376
TI  - The mechanism and high-free-energy transition state of lac repressor-lac operator
      interaction.
AB  - Significant, otherwise-unavailable information about mechanisms and transition
      states (TS) of protein folding and binding is obtained from solute effects on
      rate constants. Here we characterize TS for lac repressor(R)-lac operator(O)
      binding by analyzing effects of RO-stabilizing and RO-destabilizing solutes on
      association (ka) and dissociation (kd) rate constants. RO-destabilizing solutes
      (urea, KCl) reduce ka comparably (urea) or more than (KCl) they increase kd,
      demonstrating that they destabilize TS relative to reactants and RO, and that TS
      exhibits most of the Coulombic interactions between R and O. Strikingly, three
      solutes which stabilize RO by favoring burial/dehydration of amide oxygens and
      anionic phosphate oxygens all reduce kd without affecting ka significantly. The
      lack of stabilization of TS by these solutes indicates that O phosphates remain
      hydrated in TS and that TS preferentially buries aromatic carbons and amide
      nitrogens while leaving amide oxygens exposed. In our proposed mechanism, DNA
      binding-domains (DBD) of R insert in major grooves of O pre-TS, forming most
      Coulombic interactions of RO and burying aromatic carbons. Nucleation of hinge
      helices creates TS, burying sidechain amide nitrogens. Post-TS, hinge helices
      assemble and the DBD-hinge helix-O-DNA module docks on core repressor, partially
      dehydrating phosphate oxygens and tightening all interfaces to form RO.

PMID- 29036378
TI  - The effect of costs on Kenyan households' demand for medical care: why time and
      distance matter.
AB  - In an environment of constrained resources, policymakers must identify solutions
      for financing and delivering health services that are efficient and sustainable.
      However, such solutions require that policymakers understand the complex
      interaction between household utilization patterns, factors influencing household
      medical decisions, and provider performance. This study examined whether and
      under what conditions out-of-pocket, transportation, and time costs influenced
      Kenyan households' choice of medical provider for childhood diarrhoeal illnesses.
      It compared these decisions with the actual cost and quality of those providers
      to assess strategies for increasing the utilization of high quality, low-cost
      primary care. This study analyzed nationally-representative survey data through
      several multinomial nested logit models. On average, time costs accounted for the
      greatest share of total costs. Households spent the most time and transportation
      costs utilizing public care, yet were more likely to incur catastrophic time and
      out-of-pocket costs seeking private care for their child's diarrhoeal illness.
      Out-of-pocket, transportation, and time costs influenced households' choice of
      provider, though demand was cost inelastic and households were most responsive to
      transportation costs. Poorer households were the most responsive to changes in
      all cost types and most likely to self-treat or utilize informal care. Many
      households utilized informal care that, relative to formal care, cost the same
      but was of worse quality-suggesting that such households were making poor medical
      decisions for their children. To achieve public policy objectives, such as
      financial risk protection for childhood illnesses and equitable access to primary
      care, policymakers could focus on three areas: (1) refine financing strategies
      for further reducing household out-of-pocket costs; (2) reduce or subsidize time
      and transportation costs for households seeking public and private care; and (3)
      increase transparency of costs and quality to improve household decisions.

PMID- 29036379
TI  - PHOTOLUMINESCENCE, THERMOLUMINESCENCE AND OPTICALLY STIMULATED LUMINESCENCE
      STUDIES IN ZINC-BASED FLUOROPERVOSKITES.
AB  - The optically stimulated luminescence, thermoluminescence and photoluminescence
      in various Cu and Ag doped zinc based fluoropervoskites are studied. In all the
      samples, photoluminescence of Cu+ and Ag+ is observed which could be attributed
      to 3d94 s1<-->3d10 and 4d95 s1<-->5d10 transitions, respectively. The observed
      emission is double humped and the main emission band shifts to the lower
      wavelength side with increasing ionic size of the alkali ion. All the studied
      fluoropervoskites show reasonable OSL sensitivity. Highest sensitivity is
      observed for Cu doped ZnNaF3 and is 25% compared to commercial Al2O3:C. Weak
      thermoluminescence is observed in all samples. In all Ag doped samples the TL
      peak is observed at 200 degrees C whereas for Cu doped samples peak is observed
      at 150 degrees C, and correlated with the OSL. The samples show good linear dose
      response in the 10 mGy-1.2 Gy range and show good reusability characteristics.
      This study will lead to the development of zinc-based fluoropervoskite phosphors
      for the radiation dosimetry using OSL.

PMID- 29036380
TI  - MICRODOSIMETRIC SIMULATIONS OF CARBON IONS USING THE MONTE CARLO CODE FLUKA.
AB  - Therapeutic carbon ion beams produce a complex and variable radiation field that
      changes along the penetration depth due to the high density of energy loss along
      the particle track together with the secondary particles produced by nuclear
      fragmentation reactions. An accurate physical characterisation of such complex
      mixed-radiation fields can be performed by measuring microdosimetric spectra with
      mini tissue-equivalent proportional counters (mini-TEPCs), which are one of the
      most accurate devices used in experimental microdosimetry. Numerical calculations
      with Monte Carlo codes such as FLUKA can be used to supplement experimental
      microdosimetric measurements performed with TEPCs, but the nuclear cross sections
      and fragmentation models need to be benchmarked with experimental data for
      different energies and scenarios. The aim of this work is to compare experimental
      carbon microdosimetric data measured with the mini TEPC with calculated
      microdosimetry spectra obtained with FLUKA for 12C ions of 189.5 MeV/u in the
      Bragg peak region.

PMID- 29036381
TI  - Project ECHO Telementoring Intervention for Managing Chronic Pain in Primary
      Care: Insights from a Qualitative Study.
AB  - Objective: Family physicians in Canada receive little training in chronic pain
      management; concomitantly, they face increasing pressure to reduce their
      prescribing of opioids. Project ECHO Ontario Chronic Pain/Opioid Stewardship
      (ECHO) is a telementoring intervention for primary care practitioners that
      enhances their pain management skills. This qualitative study reports
      participants' experiences and assessment of ECHO. Design: An opportunistic sample
      of multidisciplinary primary care providers attending one of three residential
      weekend workshops participated in focus group discussions. Setting: University or
      hospital facilities in Toronto, Thunder Bay, and Kingston, Ontario, Canada.
      Subjects: Seventeen physicians and 20 allied health professionals. Methods: Six
      focus group discussions were conducted at three different sites during 2014 and
      2015. Transcripts were analyzed using a qualitative-descriptive approach
      involving analytic immersion in the data, reflection, and achieving consensus
      around themes discerned from transcribed discussions. Results: Findings resolved
      into five main themes: 1) challenges of managing chronic pain in primary care; 2)
      ECHO participation and improvement in patient-provider interaction and
      participant knowledge; 3) the diffusion of knowledge gained through ECHO to
      participants' colleagues and patients; 4) ECHO participation generating a sense
      of community; and 5) disadvantages associated with participating in ECHO.
      Conclusions: Managing patients with chronic pain in primary care can be
      difficult, particularly in remote or underserved practices. Project ECHO offers
      guidance to primary care practitioners for their most challenging patients,
      promotes knowledge acquisition and diffusion, and stimulates the development of a
      "community of practice."

PMID- 29036382
TI  - MusiteDeep: a deep-learning framework for general and kinase-specific
      phosphorylation site prediction.
AB  - Motivation: Computational methods for phosphorylation site prediction play
      important roles in protein function studies and experimental design. Most
      existing methods are based on feature extraction, which may result in incomplete
      or biased features. Deep learning as the cutting-edge machine learning method has
      the ability to automatically discover complex representations of phosphorylation
      patterns from the raw sequences, and hence it provides a powerful tool for
      improvement of phosphorylation site prediction. Results: We present MusiteDeep,
      the first deep-learning framework for predicting general and kinase-specific
      phosphorylation sites. MusiteDeep takes raw sequence data as input and uses
      convolutional neural networks with a novel two-dimensional attention mechanism.
      It achieves over a 50% relative improvement in the area under the precision
      recall curve in general phosphorylation site prediction and obtains competitive
      results in kinase-specific prediction compared to other well-known tools on the
      benchmark data. Availability and implementation: MusiteDeep is provided as an
      open-source tool available at https://github.com/duolinwang/MusiteDeep. Contact:
      xudong@missouri.edu. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29036384
TI  - THE RESPONSE OF A MULTI-ELEMENT TISSUE EQUIVALENT PROPORTIONAL COUNTER IN
      ACCELERATOR BASED HIGH-ALTITUDE NEUTRON FIELDS.
AB  - The response of a multi-element tissue equivalent proportional counter (METEPC)
      was investigated at the high energy neutron facility EU-CERF, in Prevessin,
      France. This facility was established specifically to provide reference neutron
      fields typical of those found at high altitude. The METEPC measurements were
      conducted along with a commercially available spherical tissue equivalent
      proportional counter (TEPC) used for comparison. The measured microdosimetric
      spectra were analyzed and compared for various measurement locations, with
      substantially different neutron energy distributions resulting from the use of
      iron or concrete shielding. The absorbed dose rate measured by the two counters
      in the dominant lower-energy neutron field locations from the iron-shielded
      target was <27%. A significant difference in the range of 32-58% was observed
      between the two counters in the higher-energy neutron field produced by the
      concrete-shielded target. Interestingly, due to a combination of factors,
      including the geometry and structure of the METEPC, values of dose-equivalent
      derived from the METEPC and the TEPC were in closer agreement (within 30%) and
      are well within acceptable limits for neutron monitoring.

PMID- 29036383
TI  - Nigral Stress-Induced Dopamine Release in Clinical High Risk and Antipsychotic
      Naive Schizophrenia.
AB  - Background: Striatal dopamine (DA) synthesis capacity and release are elevated in
      schizophrenia (SCZ) and its putative prodrome, the clinical high risk (CHR)
      state. Striatal DA function results from the activity of midbrain DA neurons
      projecting mainly from the substantia nigra (SN). Elevated stress-induced DA
      release in SCZ and CHR was observed in the striatum; however, whether it is also
      elevated in the SN is unclear. The current study aims to determine whether nigral
      DA release in response to a validated stress task is altered in CHR and in
      antipsychotic-naive SCZ. Further, we explore how DA release in the SN and
      striatum might be related. Methods: 24 CHR subjects, 9 antipsychotic-naive SCZ
      and 25 healthy volunteers (HV) underwent 2 positron emission tomography (PET)
      scans using the DA D2/3 agonist radiotracer, [11C]-(+)-PHNO, which allows
      simultaneous investigations of DA in the SN and striatum. Psychosocial stress
      induced DA release was estimated as the percentage differences in BPND (%[11C]
      (+)-PHNO displacement) between stress and sensory-motor control sessions.
      Results: We observed a significant diagnostic group by session interaction, such
      that SCZ exhibited greater stress-induced [11C]-(+)-PHNO % displacement (25.90%
      +/- 32.2%; mean +/- SD), as compared to HVs (-10.94% +/- 27.1%). Displacement in
      CHRs (-1.13% +/- 32.2%) did not differ significantly from either HV or SCZ.
      Conclusion: Our findings suggest that elevated nigral DA responsiveness to stress
      is observed in antipsychotic-naive SCZ.

PMID- 29036386
TI  - Uncovering the physiological mechanisms that allow nitrogen availability to
      affect drought acclimation in Catalpa bungei.

PMID- 29036385
TI  - The Latent Taxonicity of Schizotypy in Biological Siblings of Probands With
      Schizophrenia.
AB  - If schizotypy is a taxonic liability for schizophrenia with a general population
      prevalence of ~10%, it should also be taxonic among biological siblings of
      probands with schizophrenia. Moreover, assuming this is so, siblings' schizotypy
      class membership should be predicted by probands' familial load for psychotic
      disorder and clinical severity, consistent with a multifactorial polygenic
      threshold model of schizophrenia. We tested these hypotheses in the Genetic Risk
      and Outcome of Psychosis (GROUP) Study where siblings of probands (n = 792) and
      unaffected controls (n = 559) provided self-report ratings on the Community
      Assessment of Psychic Experiences (CAPE). Maximum covariance analyses of control
      group ratings led to the identification of CAPE items sensitive to nonredundant
      positive and negative schizotypy classes in the control group (prevalence = 7.9%
      and 11.1%, respectively). When the same taxonic solution was applied to siblings'
      CAPE rating, taxometric analyses yielded evidence for larger positive and
      negative schizotypy classes among siblings (prevalence = 14.1% and 21.8%,
      respectively). Whereas probands' familial loads for bipolar disorder or drug use
      disorders did not predict siblings' membership in the schizotypy classes,
      probands' familial load for psychotic disorder did. Siblings were more likely to
      be members of the positive schizotypy class where their probands were more
      severely affected. The pattern of findings is consistent with Meehl's argument
      that schizotypy reflects liability for schizophrenia.

PMID- 29036389
TI  - RADON CONCENTRATIONS IN SELECTED THERMAL WATERS IN SLOVAKIA.
AB  - Radon concentration in thermal waters used in selected spas and aqua parks in
      Slovakia was investigated. In total, 23 thermal water sources were monitored.
      Measured radon levels varied in a large interval, from 4.1 to 488 Bq l-1. High
      radon activity (180 Bq l-1) was also found in thermal potable water in fountains
      used by the patients and the public.

PMID- 29036387
TI  - Uncovering exposures responsible for birth season - disease effects: a global
      study.
AB  - Objective: Birth month and climate impact lifetime disease risk, while the
      underlying exposures remain largely elusive. We seek to uncover distal risk
      factors underlying these relationships by probing the relationship between global
      exposure variance and disease risk variance by birth season. Material and
      Methods: This study utilizes electronic health record data from 6 sites
      representing 10.5 million individuals in 3 countries (United States, South Korea,
      and Taiwan). We obtained birth month-disease risk curves from each site in a case
      control manner. Next, we correlated each birth month-disease risk curve with each
      exposure. A meta-analysis was then performed of correlations across sites. This
      allowed us to identify the most significant birth month-exposure relationships
      supported by all 6 sites while adjusting for multiplicity. We also successfully
      distinguish relative age effects (a cultural effect) from environmental
      exposures. Results: Attention deficit hyperactivity disorder was the only
      identified relative age association. Our methods identified several culprit
      exposures that correspond well with the literature in the field. These include a
      link between first-trimester exposure to carbon monoxide and increased risk of
      depressive disorder (R = 0.725, confidence interval [95% CI], 0.529-0.847), first
      trimester exposure to fine air particulates and increased risk of atrial
      fibrillation (R = 0.564, 95% CI, 0.363-0.715), and decreased exposure to sunlight
      during the third trimester and increased risk of type 2 diabetes mellitus (R = 
      0.816, 95% CI, -0.5767, -0.929). Conclusion: A global study of birth month
      disease relationships reveals distal risk factors involved in causal biological
      pathways that underlie them.

PMID- 29036388
TI  - Risk Factors for Suicidality in Patients With Schizophrenia: A Systematic Review,
      Meta-analysis, and Meta-regression of 96 Studies.
AB  - The lifetime risk of suicide and suicide attempt in patients with schizophrenia
      are 5% and 25%-50%, respectively. The current meta-analysis aims to determine
      risk factors associated with suicidality in subjects with schizophrenia. We
      searched Pubmed, Web of Science, EMBASE, and the reference lists of included
      studies. Inclusion criteria were met if an article reported a dichotomous sample
      of patients with schizophrenia with suicidal ideation, attempted suicide, or
      suicide compared to patients without. We also performed a cohort study meta
      analysis as a supplemental analysis. A total of 96 studies with 80488
      participants were included in our analysis. Depressive symptoms (P < .0001),
      Positive and Negative Symptom Scale (PANSS) general score (P < .0001) and number
      of psychiatric hospitalizations (P < .0001) were higher in patients with suicide
      ideation. History of alcohol use (P = .0001), family history of psychiatric
      illness (P < .0001), physical comorbidity (P < .0001), history of depression (P <
      .0001), family history of suicide (P < .0001), history of drug use (P = .0024),
      history of tobacco use (P = .0034), being white (P = .0022), and depressive
      symptoms (P < .0001) were the most consistent variables associated with suicide
      attempts. The first two were also significant in the cohort meta-analysis. Being
      male (P = .0005), history of attempted suicide (P < .0001), younger age (P =
      .0266), higher intelligence quotient (P < .0001), poor adherence to treatment (P
      < .0001), and hopelessness (P < .0001) were the most consistently associated with
      suicide. The first three were also significant in the cohort meta-analysis. Our
      findings may help with future development of preventive strategies to combat
      suicide. Future studies may combine the above-mentioned variables by using
      multivariate predictive analysis techniques to objectively stratify suicidality
      in schizophrenia.

PMID- 29036390
TI  - Endothelial cells modified by adenovirus vector containing nine copies hypoxia
      response elements and human vascular endothelial growth factor as the novel seed
      cells for bone tissue engineering.
AB  - Vascularization is one of the hotspots during the development of new therapeutic
      strategies for bone tissue engineering, which can alleviate hypoxic circumstance
      and prevent transplant failure. Vascular endothelial growth factor (VEGF) gene
      transfection using recombinant adenovirus (Ad) vector can effectively promote
      angiogenesis, but uncontrolled long-term continuous expression of VEGF brings
      safety concern. Here we constructed a recombinant Ad vector containing nine
      copies of HRE promoter and the hVEGF165 gene, which conserved the oxygen
      sensitivity of hypoxia-inducible factor-1/hypoxia response elements (HIF-1/HRE).
      After transfection into human umbilical vein endothelial cells (HUVEC), the
      hVEGF165 mRNA and protein levels were much higher in response to hypoxia, as
      revealed by RT-PCR and ELISA, respectively. Furthermore, Ad-9HRE-hVEGF165 vector
      effectively promoted proliferation, migration and tube formation of HUVEC under
      hypoxic conditions. Thus we believe that the Ad-9HRE-hVEGF165 vector can
      contribute to the regulation of vascularization, which may provide a new approach
      for a better control of the expression of hVEGF165 during bone tissue
      engineering.

PMID- 29036391
TI  - Improvement in Negative Symptoms and Functioning in Cognitive-Behavioral Social
      Skills Training for Schizophrenia: Mediation by Defeatist Performance Attitudes
      and Asocial Beliefs.
AB  - Psychosocial interventions have significant but modest impact on negative
      symptoms and functioning in schizophrenia. Identifying mechanisms of change in
      these interventions can inform treatment targets to strengthen these
      interventions. A number of studies have found associations between dysfunctional
      attitudes negative symptoms and functioning in schizophrenia. We previously found
      improvement in experiential negative symptoms and functioning in cognitive
      behavioral social skills training (CBSST) in participants with schizophrenia (N =
      149), and the present study examined whether improvements in CBSST in that trial
      were mediated by the group effect on defeatist performance attitudes and asocial
      beliefs. In multilevel mediation analyses, the effect of treatment group on
      experiential negative symptoms and functioning was mediated prospectively through
      defeatist attitudes but asocial beliefs only mediated effects on experiential
      negative symptoms. The findings suggest that cognitive-behavioral therapy
      interventions that target dysfunctional attitudes can lead to improvement in
      negative symptoms and functioning in schizophrenia.

PMID- 29036392
TI  - Update From the Advisory Committee on Immunization Practices.
AB  - The Advisory Committee on Immunization Practices (ACIP), a group of medical and
      public health experts, meets 3 times per year to develop recommendations for
      vaccine use in the United States. The group has 15 voting members, and each
      member's term is 4 years. ACIP members and Centers for Disease Control and
      Prevention (CDC) staff discuss the epidemiology of vaccine-preventable diseases
      and vaccine research, effectiveness, safety data, and clinical trial results.
      Representatives from the American Academy of Pediatrics (Carrie L. Byington and
      D. W. K.) and the Pediatric Infectious Diseases Society (S. T. O.) are present as
      liaisons to the ACIP. The ACIP met on June 21 to 22, 2017, to discuss catch-up
      vaccination for hepatitis A vaccine, influenza surveillance, influenza vaccine
      effectiveness, herpes zoster vaccine, the effect of varicella vaccination on the
      incidence of herpes zoster, meningococcal disease in patients taking eculizumab,
      and considerations for a potential third dose of measles, mumps, and rubella
      (MMR) vaccine to combat ongoing mumps outbreaks. Updates on dengue virus
      epidemiology, Zika virus vaccines, anthrax vaccine, yellow fever vaccine, and the
      Vaccine Adverse Event Reporting System were given also.

PMID- 29036394
TI  - Management of acute coronary syndromes in older people.

PMID- 29036393
TI  - Angiotensin Receptor Expression and Vascular Endothelial Dysfunction in
      Obstructive Sleep Apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with vascular endothelial
      dysfunction (VED) in otherwise healthy patients. The role of renin-angiotensin
      system (RAS) in the OSA induced VED is not well understood. METHODS: Recently
      diagnosed OSA patients with very low cardiovascular disease (CVD) risk
      (Framingham score <5%) were studied at diagnosis and after 12 weeks of verified
      continuous positive airway pressure (CPAP) therapy. Participants underwent biopsy
      of gluteal subcutaneous tissue at baseline and after CPAP. Microcirculatory
      endothelial expression of angiotensin receptors type-1 (AT-1) and type-2 (AT-2)
      was measured in the subcutaneous tissue using quantitative confocal microscopy
      techniques. The ex-vivo effect of AT-1 receptor blockade (ARB) on endothelial
      superoxide production was also measured before and after CPAP treatment. RESULTS:
      In OSA patients (n = 11), microcirculatory endothelial AT1 expression decreased
      from 873 (200) (fluorescence units) at baseline to 393 (59) units after 12 weeks
      of CPAP (P = 0.02). AT2 expression did not decrease significantly in these
      patients (479 (75) to 329 (58) post CPAP (P = 0.08)). The ex-vivo addition of the
      losartan to the microcirculatory endothelium resulted in decreased superoxide
      expression in the vascular walls from 14.2 (2.2) units to 4.2 (0.8) P < 0.001;
      while it had no effect on post-CPAP patient tissue (P = 0.64). CONCLUSIONS: In
      OSA patients with no to minimal CVD risk, VED is associated with upregulation of
      AT-1 expression that is reversible with CPAP. Endothelial oxidative stress was
      reversible with ARB. RAS activation may play an important role in the development
      of early CVD risk in OSA patients.

PMID- 29036395
TI  - MICRODOSIMETRIC MODELING OF THE RELATIVE LUMINESCENCE EFFICIENCY OF LiF:Mg,Ti
      (MTS) DETECTORS EXPOSED TO CHARGED PARTICLES.
AB  - A microdosimetric model has been developed to predict the relative efficiency of
      luminescent detectors for measuring different radiation qualities. The model has
      been tested for LiF:Mg,Ti (MTS) detectors exposed to charged particles from 1H to
      132Xe in the energy range 3-1000 MeV/u. The obtained results have been compared
      with experimental data present in literature showing very good agreement in case
      of calculations performed in a site size of 40 nm.

PMID- 29036398
TI  - RE: "MODELED AND PERCEIVED EXPOSURE TO RADIOFREQUENCY ELECTROMAGNETIC FIELDS FROM
      MOBILE-PHONE BASE STATIONS AND THE DEVELOPMENT OF SYMPTOMS OVER TIME IN A GENERAL
      POPULATION COHORT".

PMID- 29036397
TI  - Polyploidy influences plant-environment interactions in quaking aspen (Populus
      tremuloides Michx.).
AB  - Quaking aspen (Populus tremuloides Michx.), a widespread and keystone tree
      species in North America, experienced heat and drought stress in the years 2002
      and 2003 in the southwestern United States. This led to widespread aspen
      mortality that has altered the composition of forests, and is expected to occur
      again if climate change continues. Understanding interactions between aspen and
      its environments is essential to understanding future mortality risk in forests.
      Polyploidy, which is common in aspen, can modify plant structure and function and
      therefore plant-environment interactions, but the influence of polyploidy on
      aspen physiology is still not well understood. Furthermore, the ploidy types of
      aspen have different biogeographies, with triploids being most frequent at lower
      latitudes in generally warmer and drier climates, while the northerly populations
      are virtually 100% diploid. This suggests that ploidy-environment interactions
      differ, and could mean that the ploidy types have different vulnerabilities to
      environmental stress. In this study, to understand aspen ploidy-environment
      interactions, we measured 38 different traits important to carbon uptake, water
      loss and water-use efficiency in diploid and triploid aspen in Colorado. We found
      that triploid aspen had lower stand density, and greater leaf area, leaf mass,
      leaf mass per area, percent nitrogen content, chlorophyll content and stomatal
      size. These differences corresponded to greater potential net carbon assimilation
      (A, measured using A/Ci curves, and chlorophyll fluorescence) and stomatal
      conductance (gs) in triploids than diploids. While triploid aspen had higher
      intrinsic water-use efficiency (iWUE, calculated from measurements of delta13C in
      leaf tissue), they also had greater potential water loss from higher measured gs
      and lower stomatal sensitivity to increasing vapor pressure deficit. Therefore,
      despite greater iWUE, triploids may have lower resilience to climate-induced
      stress. We conclude that ploidy type strongly influences physiological traits and
      function, and mediates drought stress responses in quaking aspen.

PMID- 29036396
TI  - The FASTK family of proteins: emerging regulators of mitochondrial RNA biology.
AB  - The FASTK family proteins have recently emerged as key post-transcriptional
      regulators of mitochondrial gene expression. FASTK, the founding member and its
      homologs FASTKD1-5 are architecturally related RNA-binding proteins, each having
      a different function in the regulation of mitochondrial RNA biology, from mRNA
      processing and maturation to ribosome assembly and translation. In this review,
      we outline the structure, evolution and function of these FASTK proteins and
      discuss the individual role that each has in mitochondrial RNA biology. In
      addition, we highlight the aspects of FASTK research that still require more
      attention.

PMID- 29036399
TI  - Use of a crossed high alcohol preferring (cHAP) mouse model with the NIAAA-model
      of chronic-binge ethanol intake to study liver injury.
AB  - Aims: This study sought to compare mice bred to preferentially consume high
      amounts of alcohol (crossed-high alcohol preferring, cHAP) to c57BL/6 (C57) mice
      using a chronic-binge ethanol ingestion model to induce alcoholic liver disease
      (ALD). Methods: Male C57 and cHAP mice were randomized to a Lieber-DeCarli
      control (LDC) diet, Lieber-DeCarli 5% (v/v) ethanol (LDE) diet or free-choice
      between 10% (v/v) ethanol in drinking water (EtOH-DW) and DW. After 4 weeks mice
      were gavaged with either 9 g/kg maltose-dextrin (LDC+MD) or 5 g/kg EtOH
      (LDE+Binge, EtOH-DW+Binge). Nine hours later tissue and serum were collected and
      analyzed. Results: cHAP mice on EtOH-DW consumed significantly more ethanol than
      cHAP or C57 mice maintained on LDE. However, cHAP and C57 mice on the LDE+Binge
      regiment had greater hepatosteatosis and overall degree of liver injury compared
      to EtOH-DW+Binge. Changes in pro-inflammatory gene expression was more pronounced
      in cHAP mice than C57 mice. Analysis of liver enzymes revealed a robust induction
      of CYP2E1 in C57 and cHAP mice maintained on EtOH-DW+Binge or LDE+Binge. However,
      while C57 mice exhibited higher basal hepatic glutathione than cHAP mice, these
      mice appeared more susceptible to oxidative stress following LDE+Binge than cHAP
      counterparts. Conclusions: Despite cHAP mice consuming more total ethanol prior
      to gavage when maintained on EtOH-DW, LDE followed by gavage created a more
      severe model of ALD in both C57 and cHAP mice. These data suggest factors other
      than total amount of alcohol consumed affect degree of ALD development in the
      chronic-binge model in cHAP mice. Short Summary: cHAP mice voluntarily consume
      high amounts of ethanol and exhibited hepatic injury when subject to chronic
      binge ethanol feeding with the Lieber-DeCarli diet. However, hepatic injury was
      reduced in cHAP mice in a chronic-binge model following voluntary high ethanol
      consumption in drinking water.

PMID- 29036400
TI  - Prediction and modeling of pre-analytical sampling errors as a strategy to
      improve plasma NMR metabolomics data.
AB  - Motivation: Biobanks are important infrastructures for life science research.
      Optimal sample handling regarding e.g. collection and processing of biological
      samples is highly complex, with many variables that could alter sample integrity
      and even more complex when considering multiple study centers or using legacy
      samples with limited documentation on sample management. Novel means to
      understand and take into account such variability would enable high-quality
      research on archived samples. Results: This study investigated whether pre
      analytical sample variability could be predicted and reduced by modeling
      alterations in the plasma metabolome, measured by NMR, as a function of pre
      centrifugation conditions (1-36 h pre-centrifugation delay time at 4  degrees C
      and 22  degrees C) in 16 individuals. Pre-centrifugation temperature and delay
      times were predicted using random forest modeling and performance was validated
      on independent samples. Alterations in the metabolome were modeled at each
      temperature using a cluster-based approach, revealing reproducible effects of
      delay time on energy metabolism intermediates at both temperatures, but more
      pronounced at 22  degrees C. Moreover, pre-centrifugation delay at 4  degrees C
      resulted in large, specific variability at 3 h, predominantly of lipids. Pre
      analytical sample handling error correction resulted in significant improvement
      of data quality, particularly at 22  degrees C. This approach offers the
      possibility to predict pre-centrifugation delay temperature and time in biobanked
      samples before use in costly downstream applications. Moreover, the results
      suggest potential to decrease the impact of undesired, delay-induced variability.
      However, these findings need to be validated in multiple, large sample sets and
      with analytical techniques covering a wider range of the metabolome, such as LC
      MS. Availability and implementation: The sampleDrift R package is available at
      https://gitlab.com/CarlBrunius/sampleDrift. Contact: carl.brunius@chalmers.se.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29036401
TI  - The All-Rounder Sodalis: A New Bacteriome-Associated Endosymbiont of the Lygaeoid
      Bug Henestaris halophilus (Heteroptera: Henestarinae) and a Critical Examination
      of Its Evolution.
AB  - Hemipteran insects are well-known in their ability to establish symbiotic
      relationships with bacteria. Among them, heteropteran insects present an array of
      symbiotic systems, ranging from the most common gut crypt symbiosis to the more
      restricted bacteriome-associated endosymbiosis, which have only been detected in
      members of the superfamily Lygaeoidea and the family Cimicidae so far. Genomic
      data of heteropteran endosymbionts are scarce and have merely been analyzed from
      the Wolbachia endosymbiont in bed bug and a few gut crypt-associated symbionts in
      pentatomoid bugs. In this study, we present the first detailed genomic analysis
      of a bacteriome-associated endosymbiont of a phytophagous heteropteran, present
      in the seed bug Henestaris halophilus (Hemiptera: Heteroptera: Lygaeoidea). Using
      phylogenomics and genomics approaches, we have assigned the newly characterized
      endosymbiont to the Sodalis genus, named as Candidatus Sodalis baculum sp. nov.
      strain kilmister. In addition, our findings support the reunification of the
      Sodalis genus, currently divided into six different genera. We have also
      conducted comparative analyses between 15 Sodalis species that present different
      genome sizes and symbiotic relationships. These analyses suggest that Ca. Sodalis
      baculum is a mutualistic endosymbiont capable of supplying the amino acids
      tyrosine, lysine, and some cofactors to its host. It has a small genome with
      pseudogenes but no mobile elements, which indicates middle-stage reductive
      evolution. Most of the genes in Ca. Sodalis baculum are likely to be evolving
      under purifying selection with several signals pointing to the retention of the
      lysine/tyrosine biosynthetic pathways compared with other Sodalis.

PMID- 29036404
TI  - The value of prior knowledge in machine learning of complex network systems.
AB  - Motivation: Our overall goal is to develop machine-learning approaches based on
      genomics and other relevant accessible information for use in predicting how a
      patient will respond to a given proposed drug or treatment. Given the complexity
      of this problem, we begin by developing, testing and analyzing learning methods
      using data from simulated systems, which allows us access to a known ground
      truth. We examine the benefits of using prior system knowledge and investigate
      how learning accuracy depends on various system parameters as well as the amount
      of training data available. Results: The simulations are based on Boolean
      networks-directed graphs with 0/1 node states and logical node update rules-which
      are the simplest computational systems that can mimic the dynamic behavior of
      cellular systems. Boolean networks can be generated and simulated at scale, have
      complex yet cyclical dynamics and as such provide a useful framework for
      developing machine-learning algorithms for modular and hierarchical networks such
      as biological systems in general and cancer in particular. We demonstrate that
      utilizing prior knowledge (in the form of network connectivity information),
      without detailed state equations, greatly increases the power of machine-learning
      algorithms to predict network steady-state node values ('phenotypes') and
      perturbation responses ('drug effects'). Availability and implementation: Links
      to codes and datasets here: https://gray.mgh.harvard.edu/people-directory/71
      david-craft-phd. Contact: dcraft@broadinstitute.org. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29036403
TI  - CSCD: a database for cancer-specific circular RNAs.
AB  - Circular RNA (circRNA) is a large group of RNA family extensively existed in
      cells and tissues. High-throughput sequencing provides a way to view circRNAs
      across different samples, especially in various diseases. However, there is still
      no comprehensive database for exploring the cancer-specific circRNAs. We
      collected 228 total RNA or polyA(-) RNA-seq samples from both cancer and normal
      cell lines, and identified 272 152 cancer-specific circRNAs. A total of 950 962
      circRNAs were identified in normal samples only, and 170 909 circRNAs were
      identified in both tumor and normal samples, which could be further used as non
      tumor background. We constructed a cancer-specific circRNA database (CSCD,
      http://gb.whu.edu.cn/CSCD). To understand the functional effects of circRNAs, we
      predicted the microRNA response element sites and RNA binding protein sites for
      each circRNA. We further predicted potential open reading frames to highlight
      translatable circRNAs. To understand the association between the linear splicing
      and the back-splicing, we also predicted the splicing events in linear
      transcripts of each circRNA. As the first comprehensive cancer-specific circRNA
      database, we believe CSCD could significantly contribute to the research for the
      function and regulation of cancer-associated circRNAs.

PMID- 29036402
TI  - Lack of Diagnostic Pluripotentiality in Patients at Clinical High Risk for
      Psychosis: Specificity of Comorbidity Persistence and Search for Pluripotential
      Subgroups.
AB  - More than 20 years after the clinical high risk syndrome for psychosis (CHR) was
      first articulated, it remains controversial whether the CHR syndrome predicts
      onset of psychosis with diagnostic specificity or predicts pluripotential
      diagnostic outcomes. Recently, analyses of observational studies, however, have
      suggested that the CHR syndrome is not pluripotential for emergent diagnostic
      outcomes. The present report conducted additional analyses in previously reported
      samples to determine (1) whether comorbid disorders were more likely to persist
      in CHR patients compared to a comparison group of patients who responded to CHR
      recruitment efforts but did not meet criteria, termed help-seeking comparison
      subjects (HSC); and (2) whether clinically defined pluripotential CHR subgroups
      could be identified. All data were derived from 2 multisite studies in which DSM
      IV structured diagnostic interviews were conducted at baseline and at 6-month
      intervals. Across samples we observed persistence of any nonpsychotic disorder in
      80/147 CHR cases (54.4%) and in 48/84 HSC cases (57.1%, n.s.). Findings with
      persistence of anxiety, depressive, and bipolar disorders considered separately
      were similar. Efforts to discover pluripotential CHR subgroups were unsuccessful.
      These findings add additional support to the view that the CHR syndrome is not
      pluripotential for predicting various diagnostic outcomes but rather is specific
      for predicting emergent psychosis.

PMID- 29036406
TI  - Effects of computerized decision support system implementations on patient
      outcomes in inpatient care: a systematic review.
AB  - Objectives: To systematically classify the clinical impact of computerized
      clinical decision support systems (CDSSs) in inpatient care. Materials and
      Methods: Medline, Cochrane Trials, and Cochrane Reviews were searched for CDSS
      studies that assessed patient outcomes in inpatient settings. For each study, 2
      physicians independently mapped patient outcome effects to a predefined medical
      effect score to assess the clinical impact of reported outcome effects.
      Disagreements were measured by using weighted kappa and solved by consensus. An
      example set of promising disease entities was generated based on medical effect
      scores and risk of bias assessment. To summarize technical characteristics of the
      systems, reported input variables and algorithm types were extracted as well.
      Results: Seventy studies were included. Five (7%) reported reduced mortality, 16
      (23%) reduced life-threatening events, and 28 (40%) reduced non-life-threatening
      events, 20 (29%) had no significant impact on patient outcomes, and 1 showed a
      negative effect (weighted kappa: 0.72, P < .001). Six of 24 disease entity
      settings showed high effect scores with medium or low risk of bias: blood glucose
      management, blood transfusion management, physiologic deterioration prevention,
      pressure ulcer prevention, acute kidney injury prevention, and venous
      thromboembolism prophylaxis. Most of the implemented algorithms (72%) were rule
      based. Reported input variables are shared as standardized models on a metadata
      repository. Discussion and Conclusion: Most of the included CDSS studies were
      associated with positive patient outcomes effects but with substantial
      differences regarding the clinical impact. A subset of 6 disease entities could
      be filtered in which CDSS should be given special consideration at sites where
      computer-assisted decision-making is deemed to be underutilized. Registration
      number on PROSPERO: CRD42016049946.

PMID- 29036405
TI  - FOLD: a method to optimize power in meta-analysis of genetic association studies
      with overlapping subjects.
AB  - Motivation: In genetic association studies, meta-analyses are widely used to
      increase the statistical power by aggregating information from multiple studies.
      In meta-analyses, participating studies often share the same individuals due to
      the shared use of publicly available control data or accidental recruiting of the
      same subjects. As such overlapping can inflate false positive rate, overlapping
      subjects are traditionally split in the studies prior to meta-analysis, which
      requires access to genotype data and is not always possible. Fortunately,
      recently developed meta-analysis methods can systematically account for
      overlapping subjects at the summary statistics level. Results: We identify and
      report a phenomenon that these methods for overlapping subjects can yield low
      power. For instance, in our simulation involving a meta-analysis of five studies
      that share 20% of individuals, whereas the traditional splitting method achieved
      80% power, none of the new methods exceeded 32% power. We found that this low
      power resulted from the unaccounted differences between shared and unshared
      individuals in terms of their contributions towards the final statistic. Here, we
      propose an optimal summary-statistic-based method termed as FOLD that increases
      the power of meta-analysis involving studies with overlapping subjects.
      Availability and implementation: Our method is available at
      http://software.buhmhan.com/FOLD. Contact: mail: buhm.han@amc.seoul.kr.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29036407
TI  - Prognostic value of the circumferential resection margin and its definitions in
      esophageal cancer patients after neoadjuvant chemoradiotherapy.
AB  - The accepted importance of a positive circumferential resection margin (CRM)
      (defined as R1 in the TNM classification) is based on histopathology of the
      resection specimen obtained after primary surgery in esophageal cancer patients.
      The aim of this study is to look for the prognostic value of CRM after
      neoadjuvant chemoradiotherapy and to compare the clinical significance of a
      histologically CRM < 1 mm from the cut margin (Royal College of Pathologists
      definition of R1) to a positive cut margin (College of American Pathologists
      definition of R1) and to >=1 mm margin (R0) resections in patients with ypT3
      esophageal tumors after neoadjuvant chemoradiotherapy. Between 2000 and 2014, 458
      patients who received esophagectomy after neoadjuvant chemoradiation therapy were
      selected. Overall (OS) and disease-free survival (DFS) were calculated by means
      of Kaplan-Meier curves and compared by Cox regression analysis. There were 163
      (35.9%) patients who had a ypT3 tumor; in 118 (72.4%) resection was complete
      (R0). In 37 (22.7%) patients a CRM < 1 mm was found and 8 (4.9%) had a
      circumferential R1-resection. CRM involvement was inversely correlated with tumor
      regression grading, lymph node capsular involvement, and number of positive lymph
      nodes. On univariate analysis, no statistically significant difference was found
      between R0-resection and CRM < 1 mm (P = 0.103) for OS, but DFS showed a
      significant difference (P = 0.025). Circumferential R1-resections showed a
      significant difference compared to R0-resections for OS and DFS (both P = 0.002).
      In multivariate analysis, extracapsular lymph node involvement and
      circumferential R1-resection were withheld as independent prognosticators for OS,
      whereas extracapsular lymph node involvement, absence of regression on the
      primary tumor and circumferential R1-resection were withheld for DFS. After
      correcting for different variables in the multivariate model, CRM < 1 mm showed
      no statistical difference compared to R0-resections neither for OS nor for DFS.
      After neoadjuvant chemoradiotherapy, CRM is correlated with biological behavior
      of the tumor and with therapy response. Furthermore it is an independent
      prognosticator for OS and DFS. However CRM < 1 mm itself is no independent
      prognosticator for OS nor DFS survival in multivariable analysis. These results
      suggest that the definition of R1-resection should be limited to true invasion of
      the section plane.

PMID- 29036408
TI  - Physiological differences between root suckers and saplings enlarge the
      regeneration niche in Eucryphia cordifolia Cav.
AB  - Many clonal plants produce vegetative recruits that remain connected to the
      parent plant. Such connections permit resource sharing among ramets, explaining
      the high survival rates of vegetative recruits during establishment under
      suboptimal conditions for sexual regeneration. We propose that differences in the
      regeneration niches of sexual and vegetative recruits reflect different
      physiological adjustments caused by parental supply of resources to the ramets.
      We conducted ecophysiological measurements in saplings and root suckers of
      Eucryphia cordifolia Cav., a tree species of the temperate rainforest of southern
      South America. We compared the following traits of saplings and suckers: gas
      exchange at the leaf level, crown architecture, daily crown carbon balance,
      biomass allocation to above-ground tissues (leaf-to-stem mass ratio, leaf mass
      area and leaf area ratio), xylem anatomy traits (lumen vessel fraction, vessel
      density and size) and stem ring width. We also correlated the growth rates of
      saplings and suckers with relevant environmental data (light and climate).
      Saplings showed morphological, architectural and physiological traits that
      enhance daily crown carbon balance and increase water-use efficiency, in order to
      supply their growth demands while minimizing water loss per unit of carbon
      gained. The radial growth of saplings diminished under dry conditions, which
      suggests a strong stomatal sensitivity to water availability. Suckers have low
      stomatal conductance, likely because the carbon supplied by the parent plant
      diminishes the necessity of high rates of photosynthesis. The low responsiveness
      of sucker growth to temporal changes in water availability also supports the
      existence of parental supply. The physiological differences between sexual and
      vegetative recruits satisfactorily explain the ecological niche of E. cordifolia,
      with saplings restricted to more closed and humid sites.

PMID- 29036409
TI  - Structure of an innexin gap junction channel and cryo-EM sample preparation.
AB  - Gap junction channels are essential for mediating intercellular communication in
      most multicellular organisms. Two gene families encode gap junction channels,
      innexin and connexin. Although the sequence similarity between these two families
      based on bioinformatics is not conclusively determined, the gap junction channels
      encoded by these two gene families are structurally and functionally analogous.
      We recently reported an atomic structure of an invertebrate innexin gap junction
      channel using single-particle cryo-electron microscopy. Our findings revealed
      that connexin and innexin families share several structural properties with
      regard to their monomeric and oligomeric structures, while simultaneously
      suggesting a diversity of gap junction channels in nature. This review summarizes
      cutting-edge progress toward determining an innexin gap junction channel
      structure, as well as essential tips for preparing cryo-electron microscopy
      samples for high-resolution structural analysis of an innexin gap junction
      channel.

PMID- 29036410
TI  - SPRINT: an SNP-free toolkit for identifying RNA editing sites.
AB  - Motivation: RNA editing generates post-transcriptional sequence alterations.
      Detection of RNA editing sites (RESs) typically requires the filtering of SNVs
      called from RNA-seq data using an SNP database, an obstacle that is difficult to
      overcome for most organisms. Results: Here, we present a novel method named
      SPRINT that identifies RESs without the need to filter out SNPs. SPRINT also
      integrates the detection of hyper RESs from remapped reads, and has been fully
      automated to any RNA-seq data with reference genome sequence available. We have
      rigorously validated SPRINT's effectiveness in detecting RESs using RNA-seq data
      of samples in which genes encoding RNA editing enzymes are knock down or over
      expressed, and have also demonstrated its superiority over current methods. We
      have applied SPRINT to investigate RNA editing across tissues and species, and
      also in the development of mouse embryonic central nervous system. A web resource
      (http://sprint.tianlab.cn) of RESs identified by SPRINT has been constructed.
      Availability and implementation: The software and related data are available at
      http://sprint.tianlab.cn. Contact: weidong.tian@fudan.edu.cn. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29036411
TI  - Relative Validity of Nutrient Intakes Assessed by Questionnaire, 24-Hour Recalls,
      and Diet Records as Compared With Urinary Recovery and Plasma Concentration
      Biomarkers: Findings for Women.
AB  - We evaluated the performance of a semiquantitative food frequency questionnaire
      (SFFQ), the Automated Self-Administered 24-Hour Dietary Recall (ASA24), and 7-day
      dietary records (7DDRs), in comparison with biomarkers, in the estimation of
      nutrient intakes among 627 women in the Women's Lifestyle Validation Study
      (United States, 2010-2012). Two paper SFFQs, 1 Web-based SFFQ, 4 ASA24s (beta
      version), 2 7DDRs, 4 24-hour urine samples, 1 doubly labeled water measurement
      (repeated among 76 participants), and 2 fasting blood samples were collected over
      a 15-month period. The dietary variables evaluated were energy, energy-adjusted
      intakes of protein, sodium, potassium, and specific fatty acids, carotenoids,
      alpha-tocopherol, retinol, and folate. In general, relative to biomarkers,
      averaged ASA24s had lower validity than the SFFQ completed at the end of the data
      collection year (SFFQ2); SFFQ2 had slightly lower validity than 1 7DDR; the
      averaged SFFQs had validity similar to that of 1 7DDR; and the averaged 7DDRs had
      the highest validity. The deattenuated correlation of energy-adjusted protein
      intake assessed by SFFQ2 with its biomarker was 0.46, similar to its correlation
      with 7DDRs (deattenuated r = 0.54). These data indicate that the SFFQ2 provides
      reasonably valid measurements of energy-adjusted intake for most of the nutrients
      assessed in our study, consistent with earlier conclusions derived using 7DDRs as
      the comparison method. The ASA24 needs further evaluation for use in large
      population studies, but an average of 3 days of measurement will not be
      sufficient for some important nutrients.

PMID- 29036412
TI  - Radiomic subtyping improves disease stratification beyond key molecular,
      clinical, and standard imaging characteristics in patients with glioblastoma.
AB  - Background: The purpose of this study was to analyze the potential of radiomics
      for disease stratification beyond key molecular, clinical, and standard imaging
      features in patients with glioblastoma. Methods: Quantitative imaging features (n
      = 1043) were extracted from the multiparametric MRI of 181 patients with newly
      diagnosed glioblastoma prior to standard-of-care treatment (allocated to a
      discovery and a validation set, 2:1 ratio). A subset of 386/1043 features were
      identified as reproducible (in an independent MRI test-retest cohort) and
      selected for analysis. A penalized Cox model with 10-fold cross-validation
      (Coxnet) was fitted on the discovery set to construct a radiomic signature for
      predicting progression-free and overall survival (PFS and OS). The incremental
      value of a radiomic signature beyond molecular (O6-methylguanine-DNA
      methyltransferase [MGMT] promoter methylation, DNA methylation subgroups),
      clinical (patient's age, KPS, extent of resection, adjuvant treatment), and
      standard imaging parameters (tumor volumes) for stratifying PFS and OS was
      assessed with multivariate Cox models (performance quantified with prediction
      error curves). Results: The radiomic signature (constructed from 8/386 features
      identified through Coxnet) increased the prediction accuracy for PFS and OS (in
      both discovery and validation sets) beyond the assessed molecular, clinical, and
      standard imaging parameters (P <= 0.01). Prediction errors decreased by 36% for
      PFS and 37% for OS when adding the radiomic signature (compared with 29% and 27%,
      respectively, with molecular + clinical features alone). The radiomic signature
      was-along with MGMT status-the only parameter with independent significance on
      multivariate analysis (P <= 0.01). Conclusions: Our study stresses the role of
      integrating radiomics into a multilayer decision framework with key molecular and
      clinical features to improve disease stratification and to potentially advance
      personalized treatment of patients with glioblastoma.

PMID- 29036413
TI  - Smooth quantile normalization.
AB  - Between-sample normalization is a critical step in genomic data analysis to
      remove systematic bias and unwanted technical variation in high-throughput data.
      Global normalization methods are based on the assumption that observed
      variability in global properties is due to technical reasons and are unrelated to
      the biology of interest. For example, some methods correct for differences in
      sequencing read counts by scaling features to have similar median values across
      samples, but these fail to reduce other forms of unwanted technical variation.
      Methods such as quantile normalization transform the statistical distributions
      across samples to be the same and assume global differences in the distribution
      are induced by only technical variation. However, it remains unclear how to
      proceed with normalization if these assumptions are violated, for example, if
      there are global differences in the statistical distributions between biological
      conditions or groups, and external information, such as negative or control
      features, is not available. Here, we introduce a generalization of quantile
      normalization, referred to as smooth quantile normalization (qsmooth), which is
      based on the assumption that the statistical distribution of each sample should
      be the same (or have the same distributional shape) within biological groups or
      conditions, but allowing that they may differ between groups. We illustrate the
      advantages of our method on several high-throughput datasets with global
      differences in distributions corresponding to different biological conditions. We
      also perform a Monte Carlo simulation study to illustrate the bias-variance
      tradeoff and root mean squared error of qsmooth compared to other global
      normalization methods. A software implementation is available from
      https://github.com/stephaniehicks/qsmooth.

PMID- 29036414
TI  - Monthly variation in mammographic screening attendance in Norway.
AB  - Breast Cancer Awareness Month (BCAM) increases screening attendance in the USA.
      However, this effect has not been investigated in Europe, where organized
      screening is widespread. We examined monthly attendance within the Norwegian
      Breast Cancer Screening Programme, 2005-15. Relative to October, the odds of
      attending screening in January, February, March, August, September or December
      were slightly decreased (ORadj 0.93-0.98, P <= 0.003 for all). BCAM may
      marginally increase attendance in October but seasonal factors such as weather
      may also explain this observed variation. Furthermore, it is possible that
      organized screening with predetermined appointments evens out the effect BCAM has
      on screening attendance.

PMID- 29036415
TI  - Transfusion Transmissible Infections Among Walk-In Blood Donors at Kisumu
      Regional Blood Transfusion Centre, Kisumu County, Kenya, 2015.
AB  - Background: Transfusion transmissible infections (TTIs) are threats to blood
      safety. This study investigated TTIs among volunteer blood donors at the Kisumu
      Regional Blood Transfusion Centre (KRBTC) in Kenya. Methods: We performed a
      retrospective record review of blood donor registers at KRBTC, 2015. Walk-in
      donors accepted for donation were analyzed to determine prevalence of human
      immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV), and syphilis.
      Descriptive and associative statistics were calculated using Microsoft Excel and
      Open-Epi software. Results: The records of a total of 3690 walk-in donors were
      reviewed, and 2046 were included in the analysis. Mean age was 30 +/- 9.6 years,
      76% male, 51% married, and 80% were Kisumu residents. Seroprevalence of HIV, HBV,
      HCV, and syphilis was 2.4%, 3.1%, 2.3%, and 1%, respectively. Conclusions: HBV
      was the most common TTI among the volunteers. KRBTC should be proactive and
      address issues of donor self-exclusion, strict adherence to donor selection
      criteria, and vaccination.

PMID- 29036416
TI  - Dementia, disclosing the diagnosis.

PMID- 29036417
TI  - Coprophagous Insects and the Ecology of Infectious Diseases of Wildlife.
AB  - A diversity of macro- and microparasitic species exert strong influences on
      wildlife population density, community structure, and ecosystem functioning, all
      through their impacts on individual host fitness. Through consuming,
      manipulating, and relocating wildlife feces, over 7,000 species of coprophagous
      dung beetles interact with a staggering diversity of wildlife parasites with
      fecal-oral transmission in ways that both increase and decrease transmission.
      Here, we review the mechanisms by which dung beetles influence micro- and
      macroparasite transmission and outline a future research framework that
      integrates theory and empirical insights to advance our understanding of how
      these relationships may interact with ongoing environmental change drivers to
      further influence wildlife populations and community structure. Any organism that
      significantly influences parasite transmission will impact multiple levels of
      biological organization. Therefore, improving our understanding of the role of
      dung beetle interactions within disease ecology will be key to future efforts to
      understand the overall dynamics of infection in wildlife and how parasites
      contribute to the maintenance of ecosystem structure and function and
      evolutionary processes in wild animals.

PMID- 29036418
TI  - Spironolactone-induced degradation of the TFIIH core complex XPB subunit
      suppresses NF-kappaB and AP-1 signalling.
AB  - Aims: Spironolactone (SPL) improves endothelial dysfunction and survival in heart
      failure. Immune modulation, including poorly understood mineralocorticoid
      receptor (MR)-independent effects of SPL might contribute to these benefits and
      possibly be useful in other inflammatory cardiovascular diseases such as
      pulmonary arterial hypertension. Methods and results: Using human embryonic
      kidney cells (HEK 293) expressing specific nuclear receptors, SPL suppressed NF
      kappaB and AP-1 reporter activity independent of MR and other recognized nuclear
      receptor partners. NF-kappaB and AP-1 DNA binding were not affected by SPL and
      protein synthesis blockade did not interfere with SPL-induced suppression of
      inflammatory signalling. In contrast, proteasome blockade to inhibit degradation
      of xeroderma pigmentosum group B complementing protein (XPB), a subunit of the
      general transcription factor TFIIH, or XPB overexpression both prevented SPL
      mediated suppression of inflammation. Similar to HEK 293 cells, a proteasome
      inhibitor blocked XPB loss and SPL suppression of AP-1 induced target genes in
      human pulmonary artery endothelial cells (PAECs). Unlike SPL, eplerenone (EPL)
      did not cause XPB degradation and failed to similarly suppress inflammatory
      signalling. SPL combined with siRNA XPB knockdown further reduced XPB protein
      levels and had the greatest effect on PAEC inflammatory gene transcription. Using
      chromatin-immunoprecipitation, PAEC target gene susceptibility to SPL was
      associated with low basal RNA polymerase II (RNAPII) occupancy and TNFalpha
      induced RNAPII and XPB recruitment. XP patient-derived fibroblasts carrying an N
      terminal but not C-terminal XPB mutations were insensitive to both SPL-mediated
      XPB degradation and TNFalpha-induced target gene suppression. Importantly, SPL
      treatment decreased whole lung XPB protein levels in a monocrotaline rat model of
      pulmonary hypertension and reduced inflammatory markers in an observational
      cohort of PAH patients. Conclusion: SPL has important anti-inflammatory effects
      independent of aldosterone and MR, not shared with EPL. Drug-induced, proteasome
      dependent XPB degradation may be a useful therapeutic approach in cardiovascular
      diseases driven by inflammation.

PMID- 29036419
TI  - An accurate algorithm for the detection of DNA fragments from dilution pool
      sequencing experiments.
AB  - Motivation: The short read lengths of current high-throughput sequencing
      technologies limit the ability to recover long-range haplotype information.
      Dilution pool methods for preparing DNA sequencing libraries from high molecular
      weight DNA fragments enable the recovery of long DNA fragments from short
      sequence reads. These approaches require computational methods for identifying
      the DNA fragments using aligned sequence reads and assembling the fragments into
      long haplotypes. Although a number of computational methods have been developed
      for haplotype assembly, the problem of identifying DNA fragments from dilution
      pool sequence data has not received much attention. Results: We formulate the
      problem of detecting DNA fragments from dilution pool sequencing experiments as a
      genome segmentation problem and develop an algorithm that uses dynamic
      programming to optimize a likelihood function derived from a generative model for
      the sequence reads. This algorithm uses an iterative approach to automatically
      infer the mean background read depth and the number of fragments in each pool.
      Using simulated data, we demonstrate that our method, FragmentCut, has 25-30%
      greater sensitivity compared with an HMM based method for fragment detection and
      can also detect overlapping fragments. On a whole-genome human fosmid pool
      dataset, the haplotypes assembled using the fragments identified by FragmentCut
      had greater N50 length, 16.2% lower switch error rate and 35.8% lower mismatch
      error rate compared with two existing methods. We further demonstrate the greater
      accuracy of our method using two additional dilution pool datasets. Availability
      and implementation: FragmentCut is available from https://bansal
      lab.github.io/software/FragmentCut. Contact: vibansal@ucsd.edu. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29036421
TI  - LRCstats, a tool for evaluating long reads correction methods.
AB  - Motivation: Third-generation sequencing (TGS) platforms that generate long reads,
      such as PacBio and Oxford Nanopore technologies, have had a dramatic impact on
      genomics research. However, despite recent improvements, TGS reads suffer from
      high-error rates and the development of read correction methods is an active
      field of research. This motivates the need to develop tools that can evaluate the
      accuracy of noisy long reads correction tools. Results: We introduce LRCstats, a
      tool that measures the accuracy of long reads correction tools. LRCstats takes
      advantage of long reads simulators that provide each simulated read with an
      alignment to the reference genome segment they originate from, and does not rely
      on a step of mapping corrected reads onto the reference genome. This allows for
      the measurement of the accuracy of the correction while being consistent with the
      actual errors introduced in the simulation process used to generate noisy reads.
      We illustrate the usefulness of LRCstats by analyzing the accuracy of four hybrid
      correction methods for PacBio long reads over three datasets. Availability and
      implementation: https://github.com/cchauve/lrcstats. Contact: laseanl@sfu.ca or
      cedric.chauve@sfu.ca. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29036422
TI  - FLUKA-BASED MONTE CARLO INVESTIGATION OF MICRODOSIMETRIC DISTRIBUTIONS OF
      TELECOBALT BEAM.
AB  - FLUKA-based Monte Carlo calculations of microdosimetric distributions in water
      phantom involving a walled spherical Tissue-Equivalent Proportional Counter
      filled with tissue-equivalent propane gas have been studied for an indigenously
      developed telecobalt machine. The simulated site size considered in the study was
      2 MUm. In the Monte Carlo calculations, field size was varied from 10 cm * 10 cm
      to 35 cm * 35 cm and the depth was varied as 5-20 cm. The study also includes
      calculation of microdosimetric distributions with a 30 degrees  wedge filter. The
      efficiency of the calculations was improved up to a factor of 26 by choosing
      appropriate cut off values for production and transport of electrons. The
      calculated microdosimetric distributions of telecobalt machine is distinctly
      different from that of a bare 60Co source which is attributed to the influence of
      scattered photons from the machine head and the water phantom.

PMID- 29036420
TI  - TurboFold II: RNA structural alignment and secondary structure prediction
      informed by multiple homologs.
AB  - This paper presents TurboFold II, an extension of the TurboFold algorithm for
      predicting secondary structures for multiple RNA homologs. TurboFold II augments
      the structure prediction capabilities of TurboFold by additionally providing
      multiple sequence alignments. Probabilities for alignment of nucleotide positions
      between all pairs of input sequences are iteratively estimated in TurboFold II by
      incorporating information from both the sequence identity and secondary
      structures. A multiple sequence alignment is obtained from these probabilities by
      using a probabilistic consistency transformation and a hierarchically computed
      guide tree. To assess TurboFold II, its sequence alignment and structure
      predictions were compared with leading tools, including methods that focus on
      alignment alone and methods that provide both alignment and structure prediction.
      TurboFold II has comparable alignment accuracy with MAFFT and higher accuracy
      than other tools. TurboFold II also has comparable structure prediction accuracy
      as the original TurboFold algorithm, which is one of the most accurate methods.
      TurboFold II is part of the RNAstructure software package, which is freely
      available for download at http://rna.urmc.rochester.edu under a GPL license.

PMID- 29036423
TI  - Invasive micropapillary carcinoma component is an independent prognosticator of
      poorer survival in Stage III colorectal cancer patients.
AB  - Background: Invasive micropapillary carcinoma (IMPC) is an aggressive variant of
      adenocarcinoma found in several organs. Recent studies showed that IMPC in
      colorectal cancer leads to poorer prognosis than conventional colorectal cancer;
      however, the influence of IMPC on outcomes remains unclear. The present study
      aimed to identify the clinicopathological characteristics of colorectal cancers
      with IMPCs, and to evaluate the prognostic significance of IMPCs per se. Methods:
      We retrospectively analyzed data from 837 patients with colorectal cancer who
      underwent surgical treatment. We compared the clinicopathological characteristics
      and survival outcomes of colorectal cancer patients with IMPCs to those without.
      Results: Among 837 patients, 130 (16%) had an IMPC component, including 0 (0%) of
      18, 9 (4.2%) of 215, 34 (13%) of 254, 59 (24%) of 249 and 28 (27%) of 101
      patients with TNM Stages 0, I, II, III and IV, respectively. The 3-year disease
      free survival (DFS) rates were significantly worse for Stage III patients with
      IMPC than for those without (55.3% vs. 78.7% respectively, P < 0.001), but not in
      patients with other stages. Multivariate analyses of patients with Stage III
      colorectal cancer found IMPC to be associated with significantly worse DFS (P =
      0.026), as were high CEA levels, tumor budding and TNM staging. IMPC was only
      significantly associated with tumor invasion (P = 0.045) and venous invasion (P =
      0.045) in Stage III tumors. Conclusions: Identifying IMPC components in Stage III
      colorectal cancer is crucial, as their presence is significantly associated with
      poorer survival.

PMID- 29036424
TI  - Frailty and healthcare costs-longitudinal results of a prospective cohort study.
AB  - Objective: to investigate how frailty and frailty symptoms affect healthcare
      costs in older age longitudinally. Methods: data were gathered from a prospective
      cohort study in Saarland, Germany (two waves with 3-year interval, n = 1,636 aged
      57-84 years at baseline). Frailty was assessed by the five Fried frailty
      criteria. Frailty was defined as having at least three criteria, the presence of
      1-2 criteria as 'pre-frail'. Healthcare costs were quantified based on self
      reported healthcare use in the sectors of inpatient treatment, outpatient
      treatment, professional nursing care and informal care as well as the provision
      of pharmaceuticals, medical supplies and dental prostheses. Results: while the
      onset of pre-frailty did not increase (log) total healthcare costs after
      adjusting for potential confounders including comorbidity, progression from non
      frailty to frailty was associated with an increase in total healthcare costs (for
      example, costs increased by ~54 and 101% if 3 and 4 or 5 symptoms were present,
      respectively). This association of frailty onset with increased healthcare costs
      was in particular observed in the inpatient sector and for informal nursing care.
      Among the frailty symptoms, the onset of exhaustion was associated with an
      increase in total healthcare costs, whereas changes in slowness, weakness, weight
      loss and low-physical activity were not significantly associated with an increase
      in total healthcare costs. Conclusions: our data stress the economic relevance of
      frailty in late life. Postponing or reducing frailty might be fruitful in order
      to reduce healthcare costs.

PMID- 29036425
TI  - Motif independent identification of potential RNA G-quadruplexes by G4RNA
      screener.
AB  - Motivation: G-quadruplex structures in RNA molecules are known to have regulatory
      impacts in cells but are difficult to locate in the genome. The minimal
      requirements for G-quadruplex folding in RNA (G>=3N1-7 G>=3N1-7 G>=3N1-7 G>=3) is
      being challenged by observations made on specific examples in recent years. The
      definition of potential G-quadruplex sequences has major repercussions on the
      observation of the structure since it introduces a bias. The canonical motif only
      describes a sub-population of the reported G-quadruplexes. To address these
      issues, we propose an RNA G-quadruplex prediction strategy that does not rely on
      a motif definition. Results: We trained an artificial neural network with
      sequences of experimentally validated G-quadruplexes from the G4RNA database
      encoded using an abstract definition of their sequence. This artificial neural
      network, G4NN, evaluates the similarity of a given sequence to known G
      quadruplexes and reports it as a score. G4NN has a predictive power comparable to
      the reported G richness and G/C skewness evaluations that are the current state
      of-the-art for the identification of potential RNA G-quadruplexes. We combined
      these approaches in the G4RNA screener, a program designed to manage and evaluate
      the sequences to identify potential G-quadruplexes. Availability and
      implementation: G4RNA screener is available for download at
      http://gitlabscottgroup.med.usherbrooke.ca/J-Michel/g4rna_screener. Contact: jean
      michel.garant@usherbrooke.ca or jean-pierre.perreault@usherbrooke.ca or
      michelle.scott@usherbrooke.ca. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29036428
TI  - Exocyst, exosomes, and autophagy in the regulation of Brassicaceae pollen-stigma
      interactions.
AB  - Brassicaceae pollen-stigma interactions have been extensively studied in Brassica
      and Arabidopsis species to identify cellular events triggered in the stigmatic
      papillae by pollen contact. Compatible pollinations are linked to the activation
      of basal cellular responses in the stigmatic papillae, which include calcium
      gradients, actin networks, and polarized secretion. The occurrence of these
      cellular events in stigmatic papillae coincides with the stages of pollen
      hydration and pollen tube entry into the stigmatic papillar cell wall. However,
      the form of the vesicle trafficking appears to differ between species, with
      vesicle-like structures detected in Arabidopsis species while exosomes were found
      to be secreted in Brassica species. Around the same timeframe, self-incompatible
      pollen recognition leads altered cellular responses in the stigmatic papillae to
      interfere with basal compatible pollen responses and disrupt regulated secretion,
      causing self-pollen rejection. Here, the literature on the changing cellular
      dynamics in the stigmatic papillae following pollination is reviewed and
      discussed in the context of other well-characterized examples of polarized
      secretion in plants.

PMID- 29036426
TI  - Clinical outcome of patients with the Brugada type 1 electrocardiogram without
      prophylactic implantable cardioverter defibrillator in primary prevention: a
      cumulative analysis of seven large prospective studies.
AB  - Aims: Patients with the Brugada type 1 ECG (Br type 1) without previous aborted
      sudden death (aSD) who do not have a prophylactic ICD constitute a very large
      population whose outcome is little known. The objective of this study was to
      evaluate the risk of SD or aborted SD (aSD) in these patients. Methods and
      results: We conducted a meta-analysis and cumulative analysis of seven large
      prospective studies involving 1568 patients who had not received a prophylactic
      ICD in primary prevention. Patients proved to be heterogeneous. Many were
      theoretically at low risk, in that they had a drug-induced Br type 1 (48%) and/or
      were asymptomatic (87%), Others, in contrast, had one or more risk factors.
      During a mean/median follow-up ranging from 30 to 48 months, 23 patients suffered
      SD and 1 had aSD. The annual incidence of SD/aSD was 0.5% in the total
      population, 0.9% in patients with spontaneous Br type 1 and 0.08% in those with
      drug-induced Br type 1 (P = 0.0001). The paper by Brugada et al. reported an
      incidence of SD more than six times higher than the other studies, probably as a
      result of selection bias. On excluding this paper, the annual incidence of SD/aSD
      in the remaining 1198 patients fell to 0.22% in the total population and to 0.38
      and 0.06% in spontaneous and drug-induced Br type 1, respectively. Of the 24
      patients with SD/aSD, 96% were males, the mean age was 39 +/- 15 years, 92% had
      spontaneous Br type 1, 61% had familial SD (f-SD), and only 18.2% had a previous
      syncope; 43% had a positive electrophysiological study. Multiple meta-analysis of
      individual trials showed that spontaneous Br type 1, f-SD, and previous syncope
      increased the risk of SD/aSD (RR 2.83, 2.49, and 3.03, respectively). However,
      each of these three risk factors had a very low positive predictive value (PPV)
      (1.9-3.3%), while negative predictive values (NPV) were high (98.5-99.7%). The
      incidence of SD/aSD was only slightly higher in patients with syncope than in
      asymptomatic patients (2% vs. 1.5%, P = 0.6124). Patients with SD/aSD when
      compared with the others had a mean of 1.74 vs. 0.95 risk factors (P = 0.026).
      Conclusion: (i) In patients with Br type 1 ECG without an ICD in primary
      prevention, the risk of SD/aSD is low, particularly in those with drug-induced Br
      type 1; (ii) spontaneous Br type 1, f-SD, and syncope increase the risk. However,
      each of these risk factors individually has limited clinical usefulness, owing to
      their very low PPV; (iii) patients at highest risk are those with more than one
      risk factor.

PMID- 29036427
TI  - Impact of achieved blood pressure on renal function decline and first stroke in
      hypertensive patients with chronic kidney disease.
AB  - Background: The effect of achieved blood pressure (BP) on first stroke and renal
      function decline among hypertensive patients with mild to moderate chronic kidney
      disease (CKD) is still uncertain. Methods: In total, 3230 hypertensive patients
      with estimated glomerular filtration rate 30-60 mL/min/1.73 m2 and/or proteinuria
      were included in the present analyses. Eligible participants were randomly
      assigned to a daily treatment of a combined enalapril 10 mg and folic acid 0.8 mg
      tablet or an enalapril 10 mg tablet alone. Participants were followed up every 3
      months. The study outcomes included first stroke and the progression of CKD.
      Results: The median antihypertensive treatment duration was 4.7 years. Compared
      with participants with a time-averaged on-treatment systolic blood pressure (SBP)
      of 135 to <=140 mmHg, the incidence of total first stroke [1.7% versus 3.3%;
      hazard ratio (HR), 0.51; 95% confidence interval (CI): 0.26-0.99] and ischemic
      stroke (1.3% versus 2.8%; HR, 0.46; 95% CI: 0.22-0.98) decreased significantly in
      those with a time-averaged SBP of <=135 mmHg. Furthermore, a time-averaged
      diastolic blood pressure (DBP) of <=80 mmHg, compared with a time-averaged DBP
      level of 80 to <=90 mmHg, was significantly related to a decreased risk of
      hemorrhagic stroke (0.2% versus 0.9%; HR, 0.18; 95% CI: 0.04-0.80). However,
      compared with participants with a time-averaged SBP of 135 to <=140 mmHg, a lower
      but non-significant trend of CKD progression was found in those with a time
      averaged SBP of <=130 mmHg. Conclusions: A BP treatment level of <=135/80 mmHg,
      compared with a BP treatment level of 135-140/80-90 mmHg, could lead to a
      decreased risk of first stroke in hypertensive patients with mild-to-moderate
      CKD.

PMID- 29036429
TI  - Genome re-annotation of the wild strawberry Fragaria vesca using extensive
      Illumina- and SMRT-based RNA-seq datasets.
AB  - The genome of the wild diploid strawberry species Fragaria vesca, an ideal model
      system of cultivated strawberry (Fragaria * ananassa, octoploid) and other
      Rosaceae family crops, was first published in 2011 and followed by a new assembly
      (Fvb). However, the annotation for Fvb mainly relied on ab initio predictions and
      included only predicted coding sequences, therefore an improved annotation is
      highly desirable. Here, a new annotation version named v2.0.a2 was created for
      the Fvb genome by a pipeline utilizing one PacBio library, 90 Illumina RNA-seq
      libraries, and 9 small RNA-seq libraries. Altogether, 18,641 genes (55.6% out of
      33,538 genes) were augmented with information on the 5' and/or 3' UTRs, 13,168
      (39.3%) protein-coding genes were modified or newly identified, and 7,370 genes
      were found to possess alternative isoforms. In addition, 1,938 long non-coding
      RNAs, 171 miRNAs, and 51,714 small RNA clusters were integrated into the
      annotation. This new annotation of F. vesca is substantially improved in both
      accuracy and integrity of gene predictions, beneficial to the gene functional
      studies in strawberry and to the comparative genomic analysis of other
      horticultural crops in Rosaceae family.

PMID- 29036431
TI  - Longitudinal outcomes of radiofrequency ablation versus surveillance endoscopy
      for Barrett's esophagus with low-grade dysplasia.
AB  - Radiofrequency ablation of Barrett's esophagus with low-grade dysplasia is
      recommended in recent American College of Gastroenterology guidelines, with
      endoscopic surveillance considered a reasonable alternative. Few studies have
      directly compared outcomes of radiofrequency ablation to surveillance and those
      that have are limited by short duration of follow-up. This study aims to compare
      the long-term effectiveness of radiofrequency ablation versus endoscopic
      surveillance in a large, longitudinal cohort of patients with Barrett's
      esophagus, and low-grade dysplasia.We conducted a retrospective analysis of
      patients with confirmed low-grade dysplasia at a single academic medical center
      from 1991 to 2014. Patients progressing to high-grade dysplasia or esophageal
      adenocarcinoma within one year of index LGD endoscopy were defined as missed
      dysplasia and excluded. Risk factors for progression were assessed via Cox
      proportional hazards model. Comparison of progression risk was conducted using a
      Kaplan-Meier analysis. Subset analyses were conducted to examine the effect of
      reintroducing early progressors and excluding patients diagnosed prior to the
      advent of ablative therapy. Of 173 total patients, 79 (45.7%) underwent
      radiofrequency ablation while 94 (54.3%) were untreated, with median follow up of
      90 months. Seven (8.9%) patients progressed to high-grade dysplasia or
      adenocarcinoma despite ablation, compared with 14 (14.9%) undergoing surveillance
      (P = 0.44). This effect was preserved when patients diagnosed prior to the
      introduction of radiofrequency ablation were excluded (8.9% vs 13%, P = 0.68).
      Reintroduction of patients progressing within the first year of follow-up
      resulted in a trend toward significance for ablation versus surveillance (11.1%
      vs 23.8%, P = 0.053).In conclusion, progression to high-grade dysplasia or
      adenocarcinoma was not significantly reduced in the radiofrequency ablation
      cohort when compared to surveillance. Despite recent studies suggesting the
      superiority of radiofrequency ablation in reducing progression, diligent
      endoscopic surveillance may provide similar long-term outcomes.

PMID- 29036430
TI  - Delta Vs Gamma Auditory Steady State Synchrony in Schizophrenia.
AB  - Background: Delta band (1-4 Hz) neuronal responses support the precision and
      stability of auditory processing, and a deficit in delta band synchrony may be
      relevant to auditory domain symptoms in schizophrenia patients. Methods: Delta
      band synchronization elicited by a 2.5 Hz auditory steady state response (ASSR)
      paradigm, along with those from theta (5 Hz), alpha (10 Hz), beta (20 Hz), gamma
      (40 Hz), and high gamma (80 Hz) frequency ASSR, were compared in 128 patients
      with schizophrenia, 108 healthy controls, and 55 first-degree relatives (FDR) of
      patients. Results: Delta band synchronization was significantly impaired in
      patients compared with controls (F = 18.3, P < .001). There was a significant 2.5
      Hz by 40 Hz ASSR interaction (P = .023), arising from a greater reduction of 2.5
      Hz ASSR than of 40 Hz ASSR, in patients compared with controls. Greater deficit
      in delta ASSR was associated with auditory perceptual abnormality (P = .007) and
      reduced verbal working memory (P < .001). Gamma frequency ASSR impairment was
      also significant but more modest (F = 8.7, P = .004), and this deficit was also
      present in FDR (P = .022). Conclusions: The ability to sustain delta band
      oscillation entrainment in the auditory pathway is significantly reduced in
      schizophrenia patients and appears to be clinically relevant.

PMID- 29036433
TI  - Left Ventricular Hypertrophy Predicts Cardiovascular Events in Hypertensive
      Patients With Coronary Artery Calcifications.
AB  - BACKGROUND: Coronary artery calcification (CAC) is associated with increased
      cardiovascular (CV) risk. Left ventricular hypertrophy (LVH) is an independent
      risk factor for CV events. Our aim was to estimate the relative CV risk of LVH in
      the presence of CAC. METHODS: We included asymptomatic hypertensive patients who
      were enrolled in the calcification arm of the INSIGHT (International Nifedipine
      Study Intervention as Goal for Hypertension Therapy). Patients had baseline
      echocardiography and computed tomography to assess CAC. The primary end-point was
      the first CV event. RESULTS: Two hundred and fifty-two subjects (mean age 64.7 +/
      5.5 years, 54% men) were followed for a mean of 13.3 +/- 2.6 years. 72 patients
      (28.5%) had LVH and 159 patients (63%) had CAC. During follow up, 89 patients had
      a first CV event. The rate of CV events was higher in those with than in those
      without CAC (43.4% vs. 21.5%, P < 0.01) and in those with than in those without
      LVH (44% vs. 31.6%, P < 0.01). However, LVH had no effect on CV events in the
      absence of CAC, whereas LVH almost doubled the rate of CV events (61.4% vs.
      36.5%, P < 0.01) in the presence of CAC. In comparison to patients without CAC
      and without LVH the hazard ratio for CV event in those with LVH was 1.46 (95%
      confidence interval [CI], 0.50-4.21) in those without CAC and 4.4 (95% CI, 2.02
      9.56) in those with CAC. CONCLUSIONS: LVH and CAC independently predict CV events
      in asymptomatic hypertensive patients. However, the risk of LVH is mainly
      observed in those with CAC.

PMID- 29036432
TI  - Copb2 is essential for embryogenesis and hypomorphic mutations cause human
      microcephaly.
AB  - Primary microcephaly is a congenital brain malformation characterized by a head
      circumference less than three standard deviations below the mean for age and sex
      and results in moderate to severe mental deficiencies and decreased lifespan. We
      recently studied two children with primary microcephaly in an otherwise
      unaffected family. Exome sequencing identified an autosomal recessive mutation
      leading to an amino acid substitution in a WD40 domain of the highly conserved
      Coatomer Protein Complex, Subunit Beta 2 (COPB2). To study the role of Copb2 in
      neural development, we utilized genome-editing technology to generate an allelic
      series in the mouse. Two independent null alleles revealed that Copb2 is
      essential for early stages of embryogenesis. Mice homozygous for the patient
      variant (Copb2R254C/R254C) appear to have a grossly normal phenotype, likely due
      to differences in corticogenesis between the two species. Strikingly, mice
      heterozygous for the patient mutation and a null allele (Copb2R254C/Zfn) show a
      severe perinatal phenotype including low neonatal weight, significantly increased
      apoptosis in the brain, and death within the first week of life. Immunostaining
      of the Copb2R254C/Zfnbrain revealed a reduction in layer V (CTIP2+) neurons,
      while the overall cell density of the cortex is unchanged. Moreover, neurospheres
      derived from animals with Copb2 variants grew less than control. These results
      identify a general requirement for COPB2 in embryogenesis and a specific role in
      corticogenesis. We further demonstrate the utility of CRISPR-Cas9 generated mouse
      models in the study of potential pathogenicity of variants of potential clinical
      interest.

PMID- 29036434
TI  - Novel mechanisms of eIF2B action and regulation by eIF2alpha phosphorylation.
AB  - Eukaryotic translation initiation factor 2 (eIF2) is a heterotrimeric GTPase,
      which plays a critical role in protein synthesis regulation. eIF2-GTP binds Met
      tRNAi to form the eIF2-GTP*Met-tRNAi ternary complex (TC), which is recruited to
      the 40S ribosomal subunit. Following GTP hydrolysis, eIF2-GDP is recycled back to
      TC by its guanine nucleotide exchange factor (GEF), eIF2B. Phosphorylation of the
      eIF2alpha subunit in response to various cellular stresses converts eIF2 into a
      competitive inhibitor of eIF2B, which triggers the integrated stress response
      (ISR). Dysregulation of eIF2B activity is associated with a number of
      pathologies, including neurodegenerative diseases, metabolic disorders, and
      cancer. However, despite decades of research, the underlying molecular mechanisms
      of eIF2B action and regulation remain unknown. Here we employ a combination of
      NMR, fluorescence spectroscopy, site-directed mutagenesis, and thermodynamics to
      elucidate the mechanisms of eIF2B action and its regulation by phosphorylation of
      the substrate eIF2. We present: (i) a novel mechanism for the inhibition of eIF2B
      activity, whereby eIF2alpha phosphorylation destabilizes an autoregulatory
      intramolecular interaction within eIF2alpha; and (ii) the first structural model
      for the complex of eIF2B with its substrate, eIF2-GDP, reaction intermediates,
      apo-eIF2 and eIF2-GTP, and product, TC, with direct implications for the eIF2B
      catalytic mechanism.

PMID- 29036435
TI  - The WUSCHEL-related homeobox 5a (PtoWOX5a) is involved in adventitious root
      development in poplar.
AB  - Adventitious rooting is an essential step in vegetative propagation. Currently,
      the mechanism that regulates adventitious root (AR) development in woody plants
      is poorly understood. This work demonstrates that Populus tomentosa WUSCHEL
      related homeobox 5a (PtoWOX5a) transcription factor is involved in AR development
      in poplar. PtoWOX5a was specifically expressed in the AR tip and lateral root tip
      during AR and lateral root regeneration from the stem segment. Phenotypic
      complementation experiments indicated that the PtoWOX5a can functionally
      complement AtWOX5 in quiescent center (QC) cells. Overexpression of PtoWOX5a
      introduces significant developmental phenotypes in roots and leaves, such as
      increased AR number, decreased AR length, swollen AR tip and lateral root tip,
      and decreased leaf number and area. The conserved mechanism of D-type cyclins
      (CYCD) repression mediated by WOX5 was confirmed in poplar. The co-expression
      network of PtWOX5a was constructed, which provided clues to reveal the molecular
      mechanism of PtoWOX5a in AR development in poplar. Taken together, our results
      suggest that the PtoWOX5a is involved in AR development though cooperating with a
      series of functional genes.

PMID- 29036436
TI  - Prevalence of adult overweight and obesity in 20 European countries, 2014.
AB  - Background: Monitoring obesity and overweight prevalence is important for
      assessing interventions aimed at preventing or reducing the burden of obesity.
      This study aimed to provide current data regarding the prevalence of overweight
      and obesity of adults, from 20 European countries. Methods: Participants were 34
      814 (16 482 men) adults with mean age 50.8 +/- 17.7. Data from European Social
      Survey round 7, 2014, were analysed. Body mass index (BMI) was calculated from
      self-reported height and weight. Results: The proportion of underweight was only
      2%, and 44.9% for normal weight. Overweight and obese accounted for 53.1%. More
      men than women were overweight (44.7% vs. 30.5%). Older adults were significantly
      more overweight (42.4%) and obese (20.9%) than middle age and younger adults.
      Retired people account for a greater proportion of overweight (42.0%) and obese
      (21.5%), when compared with employed, unemployed and students. People from rural
      areas were significantly more overweight (39.1 vs. 36.1%) and obese (17.0 vs.
      15.3%) than those who lived in urban areas. The estimates indicate that the
      highest prevalence of overweight was in Czech Republic (45.2%), Hungary (43.7%)
      and Lithuania (41.7%). For obesity, Slovenia (20.8%), Estonia (19.7%) and the
      United Kingdom (19.2%) were the countries with the highest prevalence.
      Conclusion: Even though data was self-reported, and individuals tend to
      overestimate their height and underestimate their weight, the prevalence of
      overweight and obesity is considered high. More than half of the European
      population is overweight and obese. This study strengthens and updates the claims
      of an excessive weight epidemic in Europe.

PMID- 29036438
TI  - A selective sphingosine-1-phosphate receptor 1 agonist SEW-2871 aggravates
      gastric cancer by recruiting myeloid-derived suppressor cells.
AB  - The immune status of tumor microenvironment in gastric cancer is poorly
      understood, which limits the development of novel strategies in this field.
      Sphingosine-1-phosphate (S1P) acts as an immune modulator, but the role of S1P in
      gastric cancer is elusive. Here, we aim to investigate S1P receptor 1 (S1P1)
      mediated effect of S1P in gastric cancer. We generated a xenograft mouse model
      and used SEW-2871, a S1P1 specific agonist to activate S1P1 signalling. Tumor
      infiltrating lymphocytes (TILs) were isolated and analysed using flow cytometry.
      Chemokine expression of tumor cells was evaluated using quantitative real-time
      polymerase chain reaction. Myeloid-derived suppressor cells (MDSCs) migration was
      assessed using Transwell chambers. SEW-2871 promoted tumor growth in our mouse
      model, and induced a higher level of MDSC and a reduced level of CD8+CD69+ T
      cells within tumor. Consistently, the anti-tumoral function of cytotoxic T
      lymphocytes was impaired in mice with SEW-2871 treatment. Additionally, SEW-2871
      enhanced expression of several MDSC recruitment-associated chemokines (CXCL12,
      CXCL5 and CCL2) in tumor cells. These chemokines facilitated MDSC migration by
      interaction with CCR2, CXCR2 and CXCR4. S1P1 signalling promoted gastric cancer
      by enhancing chemokine expression in tumor cells and recruiting MDSC to tumor
      microenvironment, which impaired anti-tumoral function of TILs.

PMID- 29036437
TI  - Fimbrins 4 and 5 Act Synergistically During Polarized Pollen Tube Growth to
      Ensure Fertility in Arabidopsis.
AB  - The germination and polar growth of pollen are prerequisite for double
      fertilization in plants. The actin cytoskeleton and its binding proteins play
      pivotal roles in pollen germination and pollen tube growth. Two homologs of the
      actin-bundling protein fimbrin, AtFIM4 and AtFIM5, are highly expressed in pollen
      in Arabidopsis and can form distinct actin architectures in vitro, but how they
      co-operatively regulate pollen germination and pollen tube growth in vivo is
      largely unknown. In this study, we explored their functions during pollen
      germination and polar growth. Histochemical analysis demonstrated that AtFIM4 was
      expressed only after pollen grain hydration and, in the early stage of pollen
      tube growth, the expression level of AtFIM4 was low, indicating that it functions
      mainly during polarized tube growth, whereas AtFIM5 had high expression levels in
      both pollen grains and pollen tubes. Atfim4/atfim5 double mutant plants had
      fertility defects including reduced silique length and seed number, which were
      caused by severe defects in pollen germination and pollen tube growth. When the
      atfim4/atfim5 double mutant was complemented with the AtFIM5 protein, the polar
      growth of pollen tubes was fully rescued; however, AtFIM4 could only partially
      restore these defects. Fluorescence labeling showed that loss of function of both
      AtFIM4 and AtFIM5 decreased the extent of actin filament bundling throughout
      pollen tubes. Collectively, our results revealed that AtFIM4 acts co-ordinately
      with AtFIM5 to organize and maintain normal actin architecture in pollen grains
      and pollen tubes to fulfill double fertilization in plants.

PMID- 29036439
TI  - Do brief alcohol interventions among unemployed at-risk drinkers increase re
      employment after 15 month?
AB  - Background: At-risk alcohol use is associated bi-directionally to unemployment,
      and decreases chances of re-employment. Brief alcohol interventions (BAI) can
      reduce at-risk alcohol use. This study aimed to investigate 15-month effects of
      BAI on unemployment among persons with at-risk alcohol use. Methods: As part of
      the randomized controlled 'Trial on proactive alcohol interventions among job
      seekers, TOPAS', 1243 18- to 64-year-old job-seekers with at-risk alcohol use
      were systematically recruited at three job agencies in Germany (2008/09), and
      randomized to (i) a stage tailored intervention based on the trans-theoretical
      model of intentional behavior change (ST), (ii) a non-stage tailored intervention
      based on the theory of planned behavior (NST) and (iii) assessment only (AO). To
      test the effects of ST and NST on employment status 15 months after baseline,
      latent growth models were calculated among those initially unemployed (n = 586).
      Results: In all three groups, unemployment significantly decreased over 15 months
      (ST: odds ratio, OR = 0.06; 95% confidence interval, CI: 0.01-0.27; NST: OR =
      0.04; 95% CI: 0.01-0.18; AO: OR = 0.05; 95% CI: 0.01-0.21). No intervention
      effects were found on unemployment. Age (P = 0.002), school education (P =
      0.001), self-rated health (P = 0.04), the Alcohol Use Disorder Identification
      Test-Consumption score (P = 0.02) and motivation to change (P = 0.04)
      significantly affected the development of unemployment over time. Conclusion:
      After 15 months, no BAI effect on unemployment was found. The mediated effect of
      BAIs on unemployment could be a longsome process needing longer follow-ups to be
      detected.

PMID- 29036440
TI  - Analysis and prediction of protein folding energy changes upon mutation by
      element specific persistent homology.
AB  - Motivation: Site directed mutagenesis is widely used to understand the structure
      and function of biomolecules. Computational prediction of mutation impacts on
      protein stability offers a fast, economical and potentially accurate alternative
      to laboratory mutagenesis. Most existing methods rely on geometric descriptions,
      this work introduces a topology based approach to provide an entirely new
      representation of mutation induced protein stability changes that could not be
      obtained from conventional techniques. Results: Topology based mutation predictor
      (T-MP) is introduced to dramatically reduce the geometric complexity and number
      of degrees of freedom of proteins, while element specific persistent homology is
      proposed to retain essential biological information. The present approach is
      found to outperform other existing methods in the predictions of globular protein
      stability changes upon mutation. A Pearson correlation coefficient of 0.82 with
      an RMSE of 0.92 kcal/mol is obtained on a test set of 350 mutation samples. For
      the prediction of membrane protein stability changes upon mutation, the proposed
      topological approach has a 84% higher Pearson correlation coefficient than the
      current state-of-the-art empirical methods, achieving a Pearson correlation of
      0.57 and an RMSE of 1.09 kcal/mol in a 5-fold cross validation on a set of 223
      membrane protein mutation samples. Availability and implementation:
      http://weilab.math.msu.edu/TML/TML-MP/. Contact: wei@math.msu.edu. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29036443
TI  - Associations of Perceived Mental Stress, Sense of Purpose in Life, and Negative
      Life Events With the Risk of Incident Herpes Zoster and Postherpetic Neuralgia:
      The SHEZ Study.
AB  - In the present population-based prospective study, we examined the associations
      of psychosocial factors with the incidence of herpes zoster (HZ) and postherpetic
      neuralgia (PHN). Data were collected from 12,359 participants (>=50 years of age)
      who answered a self-completed health questionnaire in the Shozu County of Kagawa
      Prefecture in Japan. During a 3-year follow-up between December 2008 and November
      2012, HZ and PHN were diagnosed in 400 and 79 subjects, respectively. We used Cox
      regression analysis to estimate hazard ratios of incident HZ and PHN according to
      psychosocial factors, adjusting for age, sex, histories of HZ, cancer, and
      diabetes, smoking and drinking habits, and time from disease onset to treatment.
      Men with high levels of mental stress were twice as likely to be at risk for
      incident HZ. The risk of incident HZ was approximately 60% lower among men and
      women who reported a high sense of purpose in life. Women who experienced
      negative life events-particularly changes in their work, living environment, and
      relationships-had a 2- to 3-fold higher risk of incident PHN. Psychosocial
      factors such as perceived mental stress, sense of purpose in life, and negative
      life events may contribute to the development of HZ and PHN in the general
      population.

PMID- 29036441
TI  - The role of the ER stress-response protein PERK in rhodopsin retinitis
      pigmentosa.
AB  - Mutations in rhodopsin, the light-sensitive protein of rod cells, are the most
      common cause of dominant retinitis pigmentosa (RP), a type of inherited blindness
      caused by the dysfunction and death of photoreceptor cells. The P23H mutation,
      the most frequent single cause of RP in the USA, causes rhodopsin misfolding and
      induction of the unfolded protein response (UPR), an adaptive ER stress response
      and signalling network that aims to enhance the folding and degradation of
      misfolded proteins to restore proteostasis. Prolonged UPR activation, and in
      particular the PERK branch, can reduce protein synthesis and initiate cell death
      through induction of pro-apoptotic pathways. Here, we investigated the effect of
      pharmacological PERK inhibition on retinal disease process in the P23H-1
      transgenic rat model of retinal degeneration. PERK inhibition with GSK2606414A
      led to an inhibition of eIF2alpha phosphorylation, which correlated with reduced
      ERG function and decreased photoreceptor survival at both high and low doses of
      PERK inhibitor. Additionally, PERK inhibition increased the incidence of
      inclusion formation in cultured cells overexpressing P23H rod opsin, and
      increased rhodopsin aggregation in the P23H-1 rat retina, suggesting enhanced
      P23H misfolding and aggregation. In contrast, treatment of P23H-1 rats with an
      inhibitor of eIF2alpha phosphatase, salubrinal, led to improved photoreceptor
      survival. Collectively, these data suggest the activation of PERK is part of a
      protective response to mutant rhodopsin that ultimately limits photoreceptor cell
      death.

PMID- 29036442
TI  - Global inhibition of transcription causes an increase in histone H2A.Z
      incorporation within gene bodies.
AB  - H2A.Z histone variant is an important regulator of gene transcription, which is
      enriched at regulatory regions but is also found within gene bodies. Recent
      evidence suggests that active recruitment of H2A.Z within gene bodies is required
      to induce gene repression. In contrast to this view, we show that global
      inhibition of transcription results in H2A.Z accumulation at gene transcription
      start sites, as well as within gene bodies. Our results indicate that
      accumulation of H2A.Z within repressed genes can also be a consequence of the
      repression of gene transcription rather than an active mechanism required to
      establish the repression.

PMID- 29036444
TI  - The Elephant in the room: toward a more ethical approach with accountability
      toward intended beneficiaries in humanitarian aid.
AB  - There is considerable tension between the concept of accountability to
      beneficiaries and its practice in humanitarian aid. The beneficiaries live in a
      relationship that is asymmetric; upward or horizontal accountability within the
      aid system alone-even with the best of intentions-might be short-sighted. Could
      beneficiaries be effectively involved in programing, priority setting or
      allocation of resources? Is there space for a rights-based approach in aid
      delivery and operations? The mind-set, governance and structure of operations in
      aid agencies may need significant institutional reform to share the process of
      decision-making, and to transform the current dynamic from connecting resources
      to brokering better governance, true collaboration and co-operation among all
      stakeholders. This article provides a background and overview of accountability
      in aid, sheds light onto its underlying challenges, and positive and negative
      effects through the lens of organizational and social ethics, explores practical
      and feasible ways to strengthen beneficiaries' participation and empowerment, and
      call upon aid agencies to integrate beneficiaries' views in aid operations, and
      exercise true solidarity.

PMID- 29036445
TI  - DEVELOPMENT, VALIDATION AND DEMONSTRATION OF THE NTHU FLIGHT DOSE CALCULATOR.
AB  - Galactic cosmic-ray-induced air showers constitute the largest source of
      radiation exposure for aircrew and passengers. To facilitate the evaluation of
      effective doses received by this population, a database containing dose rates of
      various radiation components in the atmosphere was established; the
      parameterization accounted for altitude, geomagnetic rigidity and solar
      modulation. Energy spectra of secondary cosmic rays and effective dose rates were
      calculated using the FLUKA Monte Carlo code. An auxiliary MATLAB program with a
      graphical user interface was developed to estimate the aviation route dose
      through interpolation and integration. The dose calculator was benchmarked by
      comparing its predictions with data from other assessments. Finally, a set of
      representative flight routes of substantial interest in Taiwan was selected and
      evaluated.

PMID- 29036446
TI  - Cardiac resynchronization therapy when no lateral pacing option exists:
      vectorcardiographic guided non-lateral left ventricular lead placement predicts
      acute hemodynamic response.
AB  - Aims: A difficult cardiac resynchronization therapy (CRT) implantation scenario
      emerges when no lateral pacing option exists. The aim of this study was to
      explore the effect of biventricular pacing (BIVP) on vectorcardiographic
      parameters in patients with a non-lateral left ventricular (LV) lead position. We
      hypothesized that perimeter and area reduction for both the QRS complex and T
      wave would predict acute CRT response. Methods and results: Twenty-six patients
      (14 ischaemic) with a mean age of 63 +/- 10 years and standard CRT indication
      underwent device implantation with continuous LV pressure registration. The LV
      lead was placed in either an anterior or apical position. Biventricular pacing
      was performed at a rate 10% above intrinsic rhythm with acute CRT response
      defined as LV DeltadP/dtmax >10%. Using this criterion 12 patients were
      identified as acute CRT responders (responders: 16.7 +/- 4.8% vs. non-responders:
      1.9 +/- 5.3%, P < 0.001). Vectorcardiographic assessment of the QRS complex and T
      wave were performed at baseline and under BIVP. Based on the observed changes in
      three-dimensional area and perimeter, DeltaQRS-area (responders: -46.7 +/- 39.6%
      vs. non-responders: 1.1 +/- 50.9%, P = 0.006) was considered as the preferred
      parameter. Receiver operating characteristic curve analysis identified -40% as
      the optimal cut-off value (sensitivity 67% and specificity 93%) for prediction of
      acute CRT response (AUC = 0.81, P < 0.01). A significant correlation was observed
      between LV DeltadP/dtmax and DeltaQRS-area (R2 = 0.37, P = 0.001). Conclusion:
      DeltaQRS-area is correlated to LV DeltadP/dtmax and predicts acute CRT response
      in patients with a non-lateral LV lead position. Assessment of DeltaQRS-area
      might be a useful tool for patient specific LV lead placement when no lateral
      pacing option exists.

PMID- 29036447
TI  - Plant exosomes: using an unconventional exit to prevent pathogen entry?
AB  - The ability to ward off filamentous pathogens, such as powdery mildew fungi, is
      one of the best studied examples of membrane trafficking-dependent disease
      resistance in plants. Here, papilla formation at the site of attack is essential
      for the pre-invasive immunity, whereas the encasement can hamper disease post
      invasively. Exosomes containing antifungal peptides and small RNAs are thought to
      play a vital role in forming papillae and encasements that block fungal growth.
      While exosomes are well described in mammals, and have been shown to play
      important roles in cell-cell communication regulating development and disease,
      their function is not well-known in plants. In this review, we focus on some of
      the recent discoveries on plant exosomes and try to link this information with
      our current understanding of how plants use this form of unconventional secretion
      to acquire this durable and effective form of resistance.

PMID- 29036448
TI  - Interleukin 6 secretion from alternatively activated macrophages promotes the
      migration of endometriotic epithelial cells.
AB  - Accumulating evidence has suggested an interaction between endometriotic cells
      and macrophages in the endometriotic microenvironment and the potential role of
      this interaction in the pathogenesis of endometriosis. However, how endometriotic
      cells communicate with macrophages to influence their function is poorly
      understood. In the present study, we found that the mRNA expression and
      production of CC chemokine ligand 2 (CCL2) were much higher in human
      endometriotic epithelial cells (11Z and 12Z) than those in human endometrial
      epithelial cells (HES). The inhibition of CCL2 action using neutralizing
      antibodies substantially suppressed macrophage migration induced by endometriotic
      epithelial cells. The endometriosis-associated macrophages (EAMs), which are the
      macrophages that are stimulated by the conditioned medium (CM) of human
      endometriotic cells, highly expressed the M2 phenotype markers (MRC1 and TREM2).
      In addition, the CM of EAMs significantly increased cell migration in 12Z cells,
      but no significant change was observed in cell growth. RT-PCR and antibody array
      analyses revealed that EAMs highly express and produce interleukin (IL) 6
      compared to macrophages stimulated by the CM of HES cells. Moreover, the EAM-CM
      induced migration and MMP2/9 expression in endometriotic cells were significantly
      attenuated by IL6 signaling inhibition. These results suggest a reciprocal
      activation of macrophages and endometriotic cells via the soluble factors CCL2
      and IL6, which may contribute to the development of endometriosis.

PMID- 29036449
TI  - Resveratrol attenuates bone cancer pain through regulating the expression levels
      of ASIC3 and activating cell autophagy.
AB  - Bone cancer pain (BCP) is one of the most common pains in patients with malignant
      cancers. The mechanism underlying BCP is largely unknown. Our previous studies
      and the increasing evidence both have shown that acid-sensing ion channels 3
      (ASIC3) is an important protein in the pathological pain state in some pain
      models. We hypothesized that the expression change of ASIC3 might be one of the
      factors related to BCP. In this study, we established the BCP model through
      intrathecally injecting rat mammary gland carcinoma cells (MRMT-1) into the left
      tibia of Sprague-Dawley female rats, and found that the BCP rats showed bone
      destruction, increased mechanical pain sensitivities and up-regulated ASIC3
      protein expression levels in L4-L6 dorsal root ganglion. Then, resveratrol, which
      was intraperitoneally injected into the BCP rats on post-operative Day 21, dose
      dependently increased the paw withdrawal threshold of BCP rats, reversed the pain
      behavior, and had an antinociceptive effect on BCP rats. In ASIC3-transfected SH
      SY5Y cells, the ASIC3 protein expression levels were regulated by resveratrol in
      a dose- and time-dependent manner. Meanwhile, resveratrol also had an
      antinociceptive effect in ASIC3-mediated pain rat model. Furthermore, resveratrol
      also enhanced the phosphorylation of AMPK, SIRT1, and LC3-II levels in ASIC3
      transfected SH-SY5Y cells, indicating that resveratrol could activate the AMPK
      SIRT1-autophagy signal pathway in ASIC3-transfected SH-SY5Y cells. In BCP rats,
      SIRT1 and LC3-II were also down-regulated. These findings provide new evidence
      for the use of resveratrol as a therapeutic treatment during BCP states.

PMID- 29036450
TI  - Crosstalk between Nitric Oxide and MPK1/2 Mediates Cold Acclimation-induced
      Chilling Tolerance in Tomato.
AB  - The participation of nitric oxide (NO) in the responses of plants towards biotic
      and abiotic stresses is well established. However, the mechanism involved
      particularly in cold acclimation-induced chilling tolerance remains elusive. Here
      we show the cold acclimation induced-chilling tolerance was associated with
      inductions of nitrate reductase (NR)-dependent NO production, S-nitrosylated
      glutathione reductase (GSNOR) activity and mitogen-activated protein kinases
      MPK1/2 activation in tomato plants. Silencing of NR resulted in decreased GSNOR
      activity and MPK1/2 activation, which subsequently compromised cold acclimation
      induced chilling tolerance. By contrast, silencing of GSNOR caused decreased NR
      activity, increased NO accumulation and MPK1/2 activation, and enhanced cold
      acclimation-induced chilling tolerance. Furthermore, co-silencing of MPK1 and
      MPK2 attenuated the NR-dependent NO production and cold acclimation-induced
      tolerance to chilling. Results from present study suggest the importance of
      MPK1/2 for the induction of NR-dependent NO generation, while the accumulation of
      nitrosylated glutathione from NO-derived reactive nitrogen species could
      potentially S-nitrosylate NR. These findings provide new insight into the
      crosstalk of NO and MPK1/2 in cold acclimation-induced chilling tolerance in
      tomato plants.

PMID- 29036451
TI  - Genetic Mapping and Phylogenetic Analysis Reveal Intraspecific Variation in Sex
      Chromosomes of the Virginian Strawberry.
AB  - With their extraordinary diversity in sexual systems, flowering plants offer
      unparalleled opportunities to understand sex determination and to reveal
      generalities in the evolution of sex chromosomes. Comparative genetic mapping of
      related taxa with good phylogenetic resolution can delineate the extent of sex
      chromosome diversity within plant groups, and lead the way to understanding the
      evolutionary drivers of such diversity. The North American octoploid wild
      strawberries provide such an opportunity. We performed linkage mapping using
      targeted sequence capture for the subdioecious western Fragaria virginiana ssp.
      platypetala and compared the location of its sex-determining region (SDR) to
      those of 2 other (sub)dioecious species, the eastern subspecies, F. virginiana
      ssp. virginiana (whose SDR is at 0-5.5 Mb on chromosome VI of the B2 subgenome),
      and the sister species F. chiloensis (whose SDR is at 37 Mb on chromosome VI of
      the Av subgenome). Male sterility was dominant in F. virginiana ssp. platypetala
      and mapped to a chromosome also in homeologous group VI. Likewise, one major
      quantitative trait locus (QTL) for female fertility overlapped the male sterility
      region. However, the SDR mapped to yet another subgenome (B1), and to a different
      location (13 Mb), but similar to the location inferred in one population of the
      naturally occurring hybrid between F. chiloensis and F. virginiana (F. *ananassa
      ssp. cuneifolia). Phylogenetic analysis of chromosomes across the octoploid taxa
      showed consistent subgenomic composition reflecting shared evolutionary history
      but also reinforced within-species variation in the SDR-carrying chromosome,
      suggesting either repeated evolution, or recent turnovers in SDR.

PMID- 29036452
TI  - A nonparametric significance test for sampled networks.
AB  - Motivation: Our work is motivated by an interest in constructing a protein
      protein interaction network that captures key features associated with
      Parkinson's disease. While there is an abundance of subnetwork construction
      methods available, it is often far from obvious which subnetwork is the most
      suitable starting point for further investigation. Results: We provide a method
      to assess whether a subnetwork constructed from a seed list (a list of nodes
      known to be important in the area of interest) differs significantly from a
      randomly generated subnetwork. The proposed method uses a Monte Carlo approach.
      As different seed lists can give rise to the same subnetwork, we control for
      redundancy by constructing a minimal seed list as the starting point for the
      significance test. The null model is based on random seed lists of the same
      length as a minimum seed list that generates the subnetwork; in this random seed
      list the nodes have (approximately) the same degree distribution as the nodes in
      the minimum seed list. We use this null model to select subnetworks which deviate
      significantly from random on an appropriate set of statistics and might capture
      useful information for a real world protein-protein interaction network.
      Availability and implementation: The software used in this paper are available
      for download at https://sites.google.com/site/elliottande/. The software is
      written in Python and uses the NetworkX library. Contact: ande.elliott@gmail.com
      or felix.reed-tsochas@sbs.ox.ac.uk. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 29036453
TI  - Heath Sector Network Governance and State-building in South Kivu, Democratic
      Republic of Congo.
AB  - Longstanding patterns of interaction exist between state and non-state actors
      seeking to improve public health in Democratic Republic of Congo (DRC). DRC is a
      weak state, and, in many cases, private actors have stepped in to fill the void
      created by the lack of state health care provision. However, the role of these
      interactions in creating a governance network in the health sector has been
      underexplored. Using data from 18 months of qualitative field research, this
      study aimed to explore governance networks in DRC's health sector, examining how
      multiple stakeholders work to manage the health system and how the resulting
      governance network has been relevant for the state-building process. The findings
      demonstrate that the health sector in South Kivu is emerging as an arena of
      networked governance based on active partnerships between state institutions and
      non-state actors. Interactions between state and non-state actors account for the
      persistence of the health sector in a setting characterized by state weakness.
      However, networked governance does not function optimally, because, although non
      state interventions fill the void where the state falls short, the DRC state has
      faced the challenge of interacting with partners with fragmented and horizontally
      competing agendas. Although weak, the shadow of state authority is present in the
      arena of stakeholders' interactions, as the state plays a determining role by
      providing a regulatory framework. Overall, the findings show that the interactive
      engagement of non-state actors contributes to improving institutional capacity
      through these actors' engagement with state institutions for health system
      management and institutional development. However, although networked health
      sector governance does contribute to state capacity, it is difficult to assess
      the real influence of these interactions on the state-building process in a
      context of critical fragility, where coordination and alignment have been
      problematic.

PMID- 29036455
TI  - JLCS medical practice guidelines for thymic tumors: summary of recommendations.
AB  - The Guideline Committee of the Japan Lung Cancer Society (JLCS) for Thymic Tumors
      published the Medical Practice Guideline for Thymic Tumors in Japanese as Chapter
      3 of the Medical Practice Guidelines for Lung Cancers according to evidence-based
      medicine in December 2016. This medical practice guideline is the first for
      thymic epithelial tumors in Japan, and comprises a set of recommendations
      covering clinical diagnosis, treatment and pathological diagnosis. Thymic
      epithelial tumors include thymoma, thymic carcinoma and thymic neuroendocrine
      tumor. The recommendations for clinical diagnosis concern detection of the
      symptoms, blood and serum tests according to clinical presentation, essential
      imaging for differential diagnosis and staging, and the necessity and methods of
      definitive diagnosis. The recommendations for treatment are dependent on tumor
      stage and recurrence status, and the treatment modalities included surgery,
      radiation therapy, chemotherapy and multimodality therapy. Those for pathological
      diagnosis deal with the handing methods of resected specimen and essential
      reporting contents for pathological diagnosis. Since data from large-scale
      analyses or clinical studies of thymic epithelial tumor are limited due to its
      low prevalence, the relevant recommendations and grading were based on available
      reported evidence and expert opinions as well as diagnostic methods and
      treatments commonly used in Japan. This report summarizes the recommendations
      concerning each topic addressed by this JLCS guideline for thymic tumors.

PMID- 29036456
TI  - Role of free DNA ends and protospacer adjacent motifs for CRISPR DNA uptake in
      Pyrococcus furiosus.
AB  - To acquire CRISPR-Cas immunity against invasive mobile genetic elements,
      prokaryotes must first integrate fragments of foreign DNA into their genomic
      CRISPR arrays for use in future invader silencing. Here, we found that the
      hyperthermophilic archaeaon, Pyrococcus furiosus, actively incorporates DNA
      fragments (spacers) from both plasmid (foreign) and host genome (self) sequences
      into its seven CRISPR loci. The majority of new spacers were derived from DNA
      immediately downstream from a 5'-CCN-3' protospacer adjacent motif (PAM) that is
      critical for invader targeting. Interestingly, spacers were preferentially
      acquired from genome or plasmid regions corresponding to active transposons,
      CRISPR loci, ribosomal RNA genes, rolling circle origins of replication, and
      areas where plasmids recombined with the host chromosome. A common feature of the
      highly sampled spacers is that they arise from DNA regions expected to undergo
      DNA nicking and/or double-strand breaks. Taken together with recent results from
      bacterial systems, our findings indicate that free DNA termini and PAMs are
      conserved features important for CRISPR spacer uptake in diverse prokaryotes and
      CRISPR-Cas systems. Moreover, lethal self-targeting by CRISPR systems may
      contribute to host genome stability by eliminating cells undergoing active
      transposon mobility or chromosomal uptake of autonomously replicating foreign
      mobile genetic elements.

PMID- 29036454
TI  - Mirror and (absence of) counter-mirror responses to action sounds measured with
      TMS.
AB  - To what extent is the mirror neuron mechanism malleable to experience? The answer
      to this question can help characterising its ontogeny and its role in social
      cognition. Some suggest that it develops through sensorimotor associations
      congruent with our own actions. Others argue for its extreme volatility that will
      encode any sensorimotor association in the environment. Here, we added to this
      debate by exploring the effects of short goal-directed 'mirror' and 'counter
      mirror' trainings (a 'mirror' training is defined as the first type of training
      encountered by the participants) on human auditory mirror motor-evoked potentials
      (MEPs). We recorded MEPs in response to two tones void of previous motor meaning,
      before and after mirror and counter-mirror trainings in which participants
      generated two tones of different pitch by performing free-choice button presses.
      The results showed that mirror MEPs, once established, were protected against an
      equivalent counter-mirror experience: they became manifest very rapidly and the
      same number of training trials that lead to the initial association did not
      suffice to reverse the MEP pattern. This steadiness of the association argues
      that, by serving direct-matching purposes, the mirror mechanism is a good
      solution for social cognition.

PMID- 29036457
TI  - Feasibility evaluation of long-term use of beta-blockers and calcium antagonists
      in patients with Brugada syndrome.
AB  - Aims: Beta-blockers (BBs) and calcium antagonists (CAs) are reported to aggravate
      ST-segment elevation in some patients with Brugada syndrome (BrS). The
      feasibility of their long-term use in BrS still remains unknown. We investigated
      the safety of long-term use of BB and CA in BrS patients. Methods and results: Of
      the 360 consecutive BrS patients, 29 [5: a history of ventricular fibrillation
      (VF), 17: syncope, 7: asymptomatic] took BB and/or CA (BB: 22, CA: 8) for more
      than 1 year for the treatment of co-morbidities such as atrial tachyarrhythmia,
      vasospastic angina, and neurally mediated syncope. The electrocardiographic
      changes and clinical outcome after the treatment were evaluated. Eleven patients
      showed type 1 electrocardiogram (ECG) at baseline. BBs and CAs were used within
      normal dosage range in all patients. After starting a BB and/or CA, type 1 ECG
      was still observed in 9 patients. There were no significant differences in the
      ECG parameters such as the amplitude of J-point, QRS duration, and corrected QT
      intervals before and after starting BB and/or CA. During follow-up of 89 +/- 65
      months after initiation of the drugs, 1 patient experienced a VF recurrence
      without significant changes of ECG parameters 2 years after BB therapy was
      started. Conclusion: Long-term intake of BB or CA within normal dosage range was
      not associated with the aggravation of ECG parameters and clinical outcome in
      patients with BrS. The use of BBs and CAs is acceptable under careful
      observation.

PMID- 29036458
TI  - Metabolic Syndrome Induces Over Expression of the Human AT1R: A Haplotype
      Dependent Effect With Implications on Cardio-Renal Function.
AB  - BACKGROUND: The transcriptional regulation of the human angiotensin receptor
      subtype 1 (AT1R) gene in pathophysiologies, like the metabolic syndrome, is
      poorly understood. The human AT1R gene has polymorphisms in its promoter that can
      be arranged in 2 haplotypes. Variants -810T, -713T, -214A, and -153A always occur
      together (Hap-I) and variants -810A, -713G, -214C, and -153G form Hap-II. We have
      hypothesized that high fat diet will alter cellular transcriptional milieu and
      increase hAT1R gene expression in a haplotype-dependent manner. This will set up
      an AT1R-mediated feed-forward loop promoting inflammation, oxidative stress, and
      hypertension in Hap-I mice. METHOD: Since Hap-I of the human AT1R gene is
      associated with hypertension in Caucasians, we generated transgenic (TG) mice
      with Hap-I and Hap-II and studied the physiological significance of high fat diet
      (HFD) on haplotype specific gene expression. Animals were fed with HFD for 20
      weeks followed by blood pressure (BP) analysis and collection of their tissues
      for molecular and biochemical studies. RESULTS: After HFD treatment, as compared
      to Hap-II, TG mice with Hap-I show increased expression of hAT1R gene and higher
      BP; suppression of antioxidant defenses (HO1, SOD1) and increased expression of
      IL-6, TNFalpha, IL-1beta, NOX1. In vivo ChIP assay has shown that transcription
      factors CEBPbeta, STAT3, and USF bind more strongly to the chromatin obtained
      from Hap-I TG mice. CONCLUSIONS: Taken together, our results suggest, that after
      HFD treatment, as compared to Hap-II, the TG mice with Hap-I overexpress the AT1R
      gene due to the stronger transcriptional activity, thus resulting in an increase
      in their BP.

PMID- 29036459
TI  - The multiple facets of root iron reduction.
AB  - The biological significance of iron (Fe) is based on its propensity to oscillate
      between the ferric and ferrous forms, a transition that also affects its phyto
      availability in soils. With the exception of grasses, Fe3+ is unavailable to
      plants. Most angiosperms employ a reduction-based Fe uptake mechanism, which
      relies on enzymatic reduction of ferric iron as an obligatory, rate-limiting step
      prior to uptake. This system functions optimally in acidic soils. Calcicole
      plants are, however, exposed to environments that are alkaline and/or have
      suboptimal availability of phosphorous, conditions under which the enzymatic
      reduction mechanism ceases to work effectively. We propose that auxiliary, non
      enzymatic Fe reduction can be of critical importance for conferring fitness to
      plants thriving in alkaline soils with low bioavailability of Fe and/or
      phosphorus.

PMID- 29036460
TI  - RADON EXHALATION FROM SOIL AND ITS DEPENDENCE FROM ENVIRONMENTAL PARAMETERS.
AB  - An automatic measuring apparatus called exhalometer for measurement of the radon
      exhalation rate from soil is introduced. It consists of a pneumatic driven
      accumulation chamber with an open bottom, a PC-based control system, six Lucas
      cells for radon measurement and sensors for environmental parameters. It allows
      moving the accumulation chamber and hereby opening or closing it. The exhalation
      rate is determined through the increase of radon in the accumulation chamber. For
      studying exhalation and the affecting factors, the exhalometer was placed at an
      undisturbed meadow for the entire year of 2015. The daily radon exhalation rate
      ranges from 2.5 to 50.7 Bq m-2 h-1 with an average of 25.3 Bq m-2 h-1. The
      exhalation rate shows daily and seasonal variations with its maximum in the
      afternoon and in spring. The dependence on several environmental parameters is
      discussed. The stable performance indicates the system's fitness for long-term
      measurements.

PMID- 29036461
TI  - Mechanisms to protect the privacy of families when using the transmission
      disequilibrium test in genome-wide association studies.
AB  - Motivation: Inappropriate disclosure of human genomes may put the privacy of
      study subjects and of their family members at risk. Existing privacy-preserving
      mechanisms for Genome-Wide Association Studies (GWAS) mainly focus on protecting
      individual information in case-control studies. Protecting privacy in family
      based studies is more difficult. The transmission disequilibrium test (TDT) is a
      powerful family-based association test employed in many rare disease studies. It
      gathers information about families (most frequently involving parents, affected
      children and their siblings). It is important to develop privacy-preserving
      approaches to disclose TDT statistics with a guarantee that the risk of family
      're-identification' stays below a pre-specified risk threshold. 'Re
      identification' in this context means that an attacker can infer that the
      presence of a family in a study. Methods: In the context of protecting family
      level privacy, we developed and evaluated a suite of differentially private (DP)
      mechanisms for TDT. They include Laplace mechanisms based on the TDT test
      statistic, P-values, projected P-values and exponential mechanisms based on the
      TDT test statistic and the shortest Hamming distance (SHD) score. Results: Using
      simulation studies with a small cohort and a large one, we showed that that the
      exponential mechanism based on the SHD score preserves the highest utility and
      privacy among all proposed DP methods. We provide a guideline on applying our DP
      TDT in a real dataset in analyzing Kawasaki disease with 187 families and 906
      SNPs. There are some limitations, including: (1) the performance of our
      implementation is slow for real-time results generation and (2) handling missing
      data is still challenging. Availability and implementation: The software dpTDT is
      available in https://github.com/mwgrassgreen/dpTDT. Contact: mengw1@stanford.edu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29036462
TI  - Drought effects on root and needle terpenoid content of a coastal and an interior
      Douglas fir provenance.
AB  - Douglas fir (Pseudotsuga menziesii) is a conifer species that stores large
      amounts of terpenoids, mainly monoterpenoids in resin ducts of various tissues.
      The effects of drought on stored leaf terpenoid concentrations in trees are
      scarcely studied and published data are partially controversial, since reduced,
      unaffected or elevated terpenoid contents due to drought have been reported. Even
      less is known on the effect of drought on root terpenoids. In the present work,
      we investigated the effect of reduced water availability on the terpenoid content
      in roots and needles of Douglas fir seedlings. Two contrasting Douglas fir
      provenances were studied: an interior provenance (var. glauca) with assumed
      higher drought resistance, and a coastal provenance (var. menziesii) with assumed
      lower drought resistance. We tested the hypothesis that both provenances show
      specific patterns of stored terpenoids and that the patterns will change in
      response to drought in both, needles and roots. We further expected stronger
      changes in the less drought tolerant coastal provenance. For this purpose, we
      performed an experiment under controlled conditions, in which the trees were
      exposed to moderate and severe drought stress. According to our expectations, the
      study revealed clear provenance-specific terpenoid patterns in needles. However,
      such patterns were not detected in the roots. Drought slightly increased the
      needle terpenoid contents of the coastal but not of the interior provenance. We
      also observed increased terpenoid abundance mainly in roots of the moderately
      stressed coastal provenance. Overall, from the observed provenance-specific
      reactions with increased terpenoid levels in trees of the coastal origin in
      response to drought, we conclude on functions of terpenoids for abiotic stress
      tolerance that might be fulfilled by other, constitutively expressed mechanisms
      in drought-adapted interior provenances.

PMID- 29036463
TI  - Multiple links between shade avoidance and auxin networks.
AB  - Auxin has emerged as a key player in the adjustment of plant morphology to the
      challenge imposed by variable environmental conditions. Shade-avoidance
      responses, including the promotion of stem and petiole growth, leaf hyponasty,
      and the inhibition of branching, involve an intimate connection between light and
      auxin signalling. Low activity of photo-sensory receptors caused by the presence
      of neighbouring vegetation enhances the activity of PHYTOCHROME INTERACTING
      FACTORs (PIFs), which directly promote the expression of genes involved in auxin
      biosynthesis, conjugation, transport, perception, and signalling. In seedlings,
      neighbour signals increase auxin levels in the foliage, which then moves to the
      stem, where it reaches epidermal tissues to promote growth. However, this model
      only partially accounts for shade-avoidance responses (which may also occur in
      the absence of increased auxin levels), and understanding the whole picture will
      require further insight into the functional significance of the multiple links
      between shade and auxin networks.

PMID- 29036464
TI  - The MIMIC Code Repository: enabling reproducibility in critical care research.
AB  - Objective: Lack of reproducibility in medical studies is a barrier to the
      generation of a robust knowledge base to support clinical decision-making. In
      this paper we outline the Medical Information Mart for Intensive Care (MIMIC)
      Code Repository, a centralized code base for generating reproducible studies on
      an openly available critical care dataset. Materials and Methods: Code is
      provided to load the data into a relational structure, create extractions of the
      data, and reproduce entire analysis plans including research studies. Results:
      Concepts extracted include severity of illness scores, comorbid status,
      administrative definitions of sepsis, physiologic criteria for sepsis, organ
      failure scores, treatment administration, and more. Executable documents are used
      for tutorials and reproduce published studies end-to-end, providing a template
      for future researchers to replicate. The repository's issue tracker enables
      community discussion about the data and concepts, allowing users to
      collaboratively improve the resource. Discussion: The centralized repository
      provides a platform for users of the data to interact directly with the data
      generators, facilitating greater understanding of the data. It also provides a
      location for the community to collaborate on necessary concepts for research
      progress and share them with a larger audience. Consistent application of the
      same code for underlying concepts is a key step in ensuring that research studies
      on the MIMIC database are comparable and reproducible. Conclusion: By providing
      open source code alongside the freely accessible MIMIC-III database, we enable
      end-to-end reproducible analysis of electronic health records.

PMID- 29036465
TI  - hnRNPM guides an alternative splicing program in response to inhibition of the
      PI3K/AKT/mTOR pathway in Ewing sarcoma cells.
AB  - Ewing sarcomas (ES) are biologically aggressive tumors of bone and soft tissues
      for which no cure is currently available. Most ES patients do not respond to
      chemotherapeutic treatments or acquire resistance. Since the PI3K/AKT/mTOR axis
      is often deregulated in ES, its inhibition offers therapeutic perspective for
      these aggressive tumors. Herein, by using splicing sensitive arrays, we have
      uncovered an extensive splicing program activated upon inhibition of the
      PI3K/AKT/mTOR signaling pathway by BEZ235. Bioinformatics analyses identified
      hnRNPM as a key factor in this response. HnRNPM motifs were significantly
      enriched in introns flanking the regulated exons and proximity of binding
      represented a key determinant for hnRNPM-dependent splicing regulation. Knockdown
      of hnRNPM expression abolished a subset of BEZ235-induced splicing changes that
      contained hnRNPM binding sites, enhanced BEZ235 cytotoxicity and limited the
      clonogenicity of ES cells. Importantly, hnRNPM up-regulation correlates with poor
      outcome in sarcoma patients. These findings uncover an hnRNPM-dependent
      alternative splicing program set in motion by inhibition of the mTOR/AKT/PI3K
      pathway in ES cells that limits therapeutic efficacy of pharmacologic inhibitors,
      suggesting that combined inhibition of the PI3K/AKT/mTOR pathway and hnRNPM
      activity may represent a novel approach for ES treatment.

PMID- 29036467
TI  - SVmine improves structural variation detection by integrative mining of
      predictions from multiple algorithms.
AB  - Motivation: Structural variation (SV) is an important class of genomic variations
      in human genomes. A number of SV detection algorithms based on high-throughput
      sequencing data have been developed, but they have various and often limited
      level of sensitivity, specificity and breakpoint resolution. Furthermore, since
      overlaps between predictions of algorithms are low, SV detection based on
      multiple algorithms, an often-used strategy in real applications, has little
      effect in improving the performance of SV detection. Results: We develop a
      computational tool called SVmine for further mining of SV predictions from
      multiple tools to improve the performance of SV detection. SVmine refines SV
      predictions by performing local realignment and assess quality of SV predictions
      based on likelihoods of the realignments. The local realignment is performed
      against a set of sequences constructed from the reference sequence near the
      candidate SV by incorporating nearby single nucleotide variations, insertions and
      deletions. A sandwich alignment algorithm is further used to improve the accuracy
      of breakpoint positions. We evaluate SVmine on a set of simulated data and real
      data and find that SVmine has superior sensitivity, specificity and breakpoint
      estimation accuracy. We also find that SVmine can significantly improve overlaps
      of SV predictions from other algorithms. Availability and implementation: SVmine
      is available at https://github.com/xyc0813/SVmine. Contact:
      ruibinxi@math.pku.edu.cn. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29036466
TI  - Insights into Epigenome Evolution from Animal and Plant Methylomes.
AB  - Evolutionary studies of DNA methylation offer insights into the mechanisms
      governing the variation of genomic DNA methylation across different species.
      Comparisons of gross levels of DNA methylation between distantly related species
      indicate that the size of the genome and the level of genomic DNA methylation are
      positively correlated. In plant genomes, this can be reliably explained by the
      genomic contents of repetitive sequences. In animal genomes, the role of
      repetitivfe sequences on genoimc DNA methylation is less clear. On a shorter
      timescale, population-level comparisons demonstrate that genetic variation can
      explain the observed variability of DNA methylation to some degree. The amount of
      DNA methylation variation that has been attributed to genetic variation in the
      human population studies so far is substantially lower than that from Arabidopsis
      population studies, but this disparity might reflect the differences in the
      computational and experimental techniques used. The effect of genetic variation
      on DNA methylation has been directly examined in mammalian systems, revealing
      several causative factors that govern DNA methylation. On the other hand, studies
      from Arabidopsis have furthered our understanding of spontaneous mutations of DNA
      methylation, termed "epimutations." Arabidopsis has an extremely high rate of
      spontaneous epimutations, which may play a major role in shaping the global DNA
      methylation landscape in this genome. Key missing information includes the
      frequencies of spontaneous epimutations in other lineages, in particular animal
      genomes, and how population-level variation of DNA methylation leads to species
      level differences.

PMID- 29036470
TI  - Corrigendum to: Evaluating the reliability, validity, acceptability, and
      practicality of SMS text messaging as a tool to collect research data: results
      from the Feeding Your Baby project.

PMID- 29036468
TI  - Exponential propagation of large circular DNA by reconstitution of a chromosome
      replication cycle.
AB  - Propagation of genetic information is a fundamental property of living organisms.
      Escherichia coli has a 4.6 Mb circular chromosome with a replication origin,
      oriC. While the oriC replication has been reconstituted in vitro more than 30
      years ago, continuous repetition of the replication cycle has not yet been
      achieved. Here, we reconstituted the entire replication cycle with 14 purified
      enzymes (25 polypeptides) that catalyze initiation at oriC, bidirectional fork
      progression, Okazaki-fragment maturation and decatenation of the replicated
      circular products. Because decatenation provides covalently closed supercoiled
      monomers that are competent for the next round of replication initiation, the
      replication cycle repeats autonomously and continuously in an isothermal
      condition. This replication-cycle reaction (RCR) propagates ~10 kb circular DNA
      exponentially as intact covalently closed molecules, even from a single DNA
      molecule, with a doubling time of ~8 min and extremely high fidelity. Very large
      DNA up to 0.2 Mb is successfully propagated within 3 h. We further demonstrate a
      cell-free cloning in which RCR selectively propagates circular molecules
      constructed by a multi-fragment assembly reaction. Our results define the minimum
      element necessary for the repetition of the chromosome-replication cycle, and
      also provide a powerful in vitro tool to generate large circular DNA molecules
      without relying on conventional biological cloning.

PMID- 29036469
TI  - Burn Pain: A Systematic and Critical Review of Epidemiology, Pathophysiology, and
      Treatment.
AB  - Objective: This review aims to examine the available literature on the
      epidemiology, pathophysiology, and treatment of burn-induced pain. Methods: A
      search was conducted on the epidemiology of burn injury and treatment of burn
      pain utilizing the database Medline, and all relevant articles were systemically
      reviewed. In addition, a critical review was performed on the pathophysiology of
      burn pain and animal models of burn pain. Results: The search on the epidemiology
      of burn injury yielded a total of 163 publications of interest, 72 of which fit
      the inclusion/exclusion criteria, with no publications providing epidemiological
      data on burn injury pain management outcomes. The search on the treatment of burn
      pain yielded a total of 213 publications, 14 of which fit the inclusion/exclusion
      criteria, highlighting the limited amount of evidence available on the treatment
      of burn-induced pain. Conclusions: The pathophysiology of burn pain is poorly
      understood, with limited clinical trials available to assess the effectiveness of
      analgesics in burn patients. Further studies are needed to identify new
      pharmacological targets and treatments for the effective management of burn
      injury pain.

PMID- 29036471
TI  - Immunization Completion in Infants Born at Low Birth Weight.
AB  - Background: Low birth weight (LBW) has been associated with underimmunization. We
      sought to understand the effect of LBW on immunization completion after
      controlling for previously hypothesized mediators, including prematurity,
      neonatal illness, well-child care, non-well-child visits, and provider
      consistency. Methods: We formed a retrospective cohort of infants born between
      2008 and 2011 with >=2 years of military healthcare follow-up. International
      Classification of Diseases, Ninth Revision codes were used to identify LBW,
      preterm birth, neonatal illnesses, well-child visits, non-well-child visits,
      provider consistency, and parental rank in the inpatient and outpatient records.
      Immunization records were extracted from both records. Logistic regression
      determined the odds of immunization completion and well-child care completion
      (ie, having had >=6 WCC visits by 15 months of age). Results: Of 135964 included
      infants, 116521 (85.7%) were completely immunized at the age of 2 years. In
      adjusted analysis, the odds of immunization completion were significantly
      decreased in infants born at LBW (odds ratio [OR], 0.88 [95% confidence interval
      (CI), 0.79-0.97]), very LBW (OR, 0.61 [95% CI, 0.48-0.77]), or extremely LBW (OR,
      0.45 [95% CI, 0.33-0.63]) or at <=32 weeks' gestation (OR, 0.76 [95% CI, 0.63
      0.92]), infants with chronic lung disease (OR, 0.63 [95% CI, 0.45-0.88]), male
      infants (OR, 0.96 [95% CI, 0.93-0.99]), and infants who experienced decreased
      provider consistency (OR, 0.92 [95% CI, 0.91-0.92]). The rate of immunization
      completion increased with the overall number of healthcare visits (OR, 1.02 [95%
      CI, 1.02-1.02]) and complete well-child care (OR, 1.80 [95% CI, 1.75-1.86]).
      However, children born LBW or preterm were significantly less likely to have
      complete well-child care. Conclusions: After adjustment for preterm birth,
      comorbid neonatal conditions, and early childhood patterns of healthcare use, LBW
      was significantly associated with immunization noncompletion in a universal
      healthcare system. Provider consistency and well-child care seem important for
      increasing immunization completion in LBW infants.

PMID- 29036473
TI  - Calmodulin/CaMKII inhibition improves intercellular communication and impulse
      propagation in the heart and is antiarrhythmic under conditions when fibrosis is
      absent.

PMID- 29036472
TI  - Measurement of nanoscale DNA translocation by uracil DNA glycosylase in human
      cells.
AB  - DNA 'sliding' by human repair enzymes is considered to be important for DNA
      damage detection. Here, we transfected uracil-containing DNA duplexes into human
      cells and measured the probability that nuclear human uracil DNA glycosylase
      (hUNG2) excised two uracil lesions spaced 10-80 bp apart in a single encounter
      without escaping the micro-volume containing the target sites. The two-site
      transfer probabilities were 100% and 54% at a 10 and 40 bp spacing, but dropped
      to only 10% at 80 bp. Enzyme trapping experiments suggested that site transfers
      over 40 bp followed a DNA 'hopping' pathway in human cells, indicating that
      authentic sliding does not occur even over this short distance. The transfer
      probabilities were much greater than observed in aqueous buffers, but similar to
      in vitro measurements in the presence of polymer crowding agents. The findings
      reveal a new role for the crowded nuclear environment in facilitating DNA damage
      detection.

PMID- 29036476
TI  - Migration of an 'injectable' loop recorder in the dorsal pleural cavity.

PMID- 29036475
TI  - Quantitative Health Risk Assessment of Indoor Radon: A Systematic Review.
AB  - Exposure to radon is a well-established cause of lung cancer in the general
      population. The aim of the present work is to identify and summarize the results
      of studies that have assessed the risk of lung cancer due to indoor radon, based
      on a systematic review of relevant published studies. Sixteen studies from 12
      different countries met eligibility criteria. Large differences in radon
      concentrations were noted between and within individual countries, and variety of
      risk models used to estimate the attributable fraction. Calculating again the
      attributable fraction in each of these studies using the same model (coefficient
      of 16% per 100 becquerels per cubic meter (Bq/m3) derived from the European
      residential radon study), the new attributable fraction of these selected studies
      ranged from 3% to 17%. Radon remains a public health concern. Information about
      radon health risks is important and efforts are needed to decrease the associated
      health problems.

PMID- 29036474
TI  - CASAnova: a multiclass support vector machine model for the classification of
      human sperm motility patterns.
AB  - The ability to accurately monitor alterations in sperm motility is paramount to
      understanding multiple genetic and biochemical perturbations impacting normal
      fertilization. Computer-aided sperm analysis (CASA) of human sperm typically
      reports motile percentage and kinematic parameters at the population level, and
      uses kinematic gating methods to identify subpopulations such as progressive or
      hyperactivated sperm. The goal of this study was to develop an automated method
      that classifies all patterns of human sperm motility during in vitro capacitation
      following the removal of seminal plasma. We visually classified CASA tracks of
      2817 sperm from 18 individuals and used a support vector machine-based decision
      tree to compute four hyperplanes that separate five classes based on their
      kinematic parameters. We then developed a web-based program, CASAnova, which
      applies these equations sequentially to assign a single classification to each
      motile sperm. Vigorous sperm are classified as progressive, intermediate, or
      hyperactivated, and nonvigorous sperm as slow or weakly motile. This program
      correctly classifies sperm motility into one of five classes with an overall
      accuracy of 89.9%. Application of CASAnova to capacitating sperm populations
      showed a shift from predominantly linear patterns of motility at initial time
      points to more vigorous patterns, including hyperactivated motility, as
      capacitation proceeds. Both intermediate and hyperactivated motility patterns
      were largely eliminated when sperm were incubated in noncapacitating medium,
      demonstrating the sensitivity of this method. The five CASAnova classifications
      are distinctive and reflect kinetic parameters of washed human sperm, providing
      an accurate, quantitative, and high-throughput method for monitoring alterations
      in motility.

PMID- 29036477
TI  - A single active site in the mariner transposase cleaves DNA strands of opposite
      polarity.
AB  - The RNase H structural fold defines a large family of nucleic acid metabolizing
      enzymes that catalyze phosphoryl transfer reactions using two divalent metal ions
      in the active site. Almost all of these reactions involve only one strand of the
      nucleic acid substrates. In contrast, cut-and-paste transposases cleave two DNA
      strands of opposite polarity, which is usually achieved via an elegant hairpin
      mechanism. In the mariner transposons, the hairpin intermediate is absent and key
      aspects of the mechanism by which the transposon ends are cleaved remained
      unknown. Here, we characterize complexes involved prior to catalysis, which
      define an asymmetric pathway for transpososome assembly. Using mixtures of wild
      type and catalytically inactive transposases, we show that all the catalytic
      steps of transposition occur within the context of a dimeric transpososome.
      Crucially, we find that each active site of a transposase dimer is responsible
      for two hydrolysis and one transesterification reaction at the same transposon
      end. These results provide the first strong evidence that a DDE/D active site can
      hydrolyze DNA strands of opposite polarity, a mechanism that has rarely been
      observed with any type of nuclease.

PMID- 29036478
TI  - Unraveling the fine-tuned lemon coloration of a pierid butterfly Catopsilia
      pomona.
AB  - Butterflies wings possess different types of scales to perform diverse functions.
      Each scale has many nano and microstructures, which interferes with light,
      resulting in unique coloration for each butterfly. Besides coloration, the
      arrangement of scales further helps in giving better survivability. Thus,
      analysis of wing pattern provides an overall idea about adaptation and activity
      of the animal. The current study deciphers the structure and composition of a
      wing of a pierid butterfly Catopsilia pomona, which remains active at 42 degrees
      C at which temperature all other butterflies face a tougher task for existence.
      In order to know the relation between survivability and adaptation in the wing,
      we have investigated the structural and physical composition of the wing of C.
      pomona under optical spectroscopy (absorption, reflectance and transmittance)
      along with microscopy techniques (optical and scanning electron microscopy),
      which are not described in earlier studies. The current findings reveal unique
      structural arrangement within scales to provide the best fit to the animal in
      variable temperature.

PMID- 29036480
TI  - Treatment of obstructive sleep apnoea-hypopnea syndrome by mandible advanced
      device reduced neuron apoptosis in frontal cortex of rabbits.
AB  - Objective: To investigate effects of mandible advanced device (MAD) therapy for
      obstructive sleep apnoea-hypopnea syndrome (OSAHS) on the neuron apoptosis and
      acetylcholine esterase activity in frontal cortex. Materials and methods: Thirty
      male New Zealand white rabbits were randomly divided into three groups (n = 10 in
      each group): group OSAHS, group MAD, and control group. Hydrophilic
      polyacrylamide gel was injected into soft palate of the animals to induce OSAHS
      in group OSAHS and group MAD. The group MAD animals wore MAD to relief the
      obstructiveness. The control group was not given any treatment. Computed
      tomography (CT) examination of the upper airway and polysomnography (PSG)
      recordings were performed in supine position. All rabbits were induced to sleep
      in a supine position for 4 to 6 hours every day and were observed for consecutive
      8 weeks. The frontal cortices of three groups were dissected and the neuron
      apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL) and flow cytometry. Acetylcholine esterase (AchE) activity in
      the frontal cortex was measured by spectrophotometry. Results: The group OSAHS
      exhibited high neuron apoptosis rate and low AchE activity than those of group
      MAD and control group. The blood oxygen saturation was negatively correlated with
      neuronal apoptosis rate and positively correlated with AchE activity. Applying
      MAD in OSAHS animals significantly improve the neuronal damage and function
      deficits by apnoea-hypoxia caused by narrowed upper airway. Conclusion: This
      study provided evidence that MAD therapy for OSAHS can significantly decrease
      neuronal apoptosis and increase AchE activity in the frontal cortex.

PMID- 29036479
TI  - A structural basis for the antibiotic resistance conferred by an N1-methylation
      of A1408 in 16S rRNA.
AB  - The aminoglycoside resistance conferred by an N1-methylation of A1408 in 16S rRNA
      by a novel plasmid-mediated methyltransferase NpmA can be a future health threat.
      In the present study, we have determined crystal structures of the bacterial
      ribosomal decoding A site with an A1408m1A antibiotic-resistance mutation both in
      the presence and absence of aminoglycosides. G418 and paromomycin both possessing
      a 6'-OH group specifically bind to the mutant A site and disturb its function as
      a molecular switch in the decoding process. On the other hand, binding of
      gentamicin with a 6'-NH3+ group to the mutant A site could not be observed in the
      present crystal structure. These observations agree with the minimum inhibitory
      concentration of aminoglycosides against Escherichia coli. In addition, one of
      our crystal structures suggests a possible conformational change of A1408 during
      the N1-methylation reaction by NpmA. The structural information obtained explains
      how bacteria acquire resistance against aminoglycosides along with a minimum of
      fitness cost by the N1-methylation of A1408 and provides novel information for
      designing the next-generation aminoglycoside.

PMID- 29036482
TI  - EFFECTIVE DOSE DUE TO TERRESTRIAL GAMMA RADIATION ESTIMATED IN SOUTHERN VIETNAM
      BY CAR-BORNE SURVEY TECHNIQUE.
AB  - Absorbed dose rates in air from natural radionuclides were measured by a car
      borne survey in southern Vietnam. The mean absorbed dose rate in air for southern
      Vietnam, which consists of the south-east region and the Mekong River Delta
      region, was 64 +/- 18 nGy h-1, while rates for the two regions were 61 +/- 17 and
      66 +/- 19 nGy h-1, respectively. These dose rates were respectively 1.2, 2.1 and
      0.9 times the measured values that were calculated on the basis of activity
      concentrations of soil samples in a previous study. It was considered that
      measured dose rate in the south-east region was influenced by the presence of
      artificial structures such as high-rise buildings and roads. The effective dose
      due to terrestrial gamma radiation for southern Vietnam was calculated to be 0.55
      mSv y-1 which is 1.2 times higher than the world-wide average of 0.48 mSv y-1.

PMID- 29036481
TI  - Identification of the direct regulon of NtcA during early acclimation to nitrogen
      starvation in the cyanobacterium Synechocystis sp. PCC 6803.
AB  - In cyanobacteria, nitrogen homeostasis is maintained by an intricate regulatory
      network around transcription factor NtcA. Although mechanisms controlling NtcA
      activity appear to be well understood, its regulon remains poorly defined. To
      determine the NtcA regulon during the early stages of nitrogen starvation for the
      model cyanobacterium Synechocystis sp. PCC 6803, we performed chromatin
      immunoprecipitation, followed by sequencing (ChIP-seq), in parallel with
      transcriptome analysis (RNA-seq). Through combining these methods, we determined
      51 genes activated and 28 repressed directly by NtcA. In addition to genes
      associated with nitrogen and carbon metabolism, a considerable number of genes
      without current functional annotation were among direct targets providing a rich
      reservoir for further studies. The NtcA regulon also included eight non-coding
      RNAs, of which Ncr1071, Syr6 and NsiR7 were experimentally validated, and their
      putative targets were computationally predicted. Surprisingly, we found
      substantial NtcA binding associated with delayed expression changes indicating
      that NtcA can reside in a poised state controlled by other factors. Indeed, a
      role of PipX as modulating factor in nitrogen regulation was confirmed for
      selected NtcA-targets. We suggest that the indicated poised state of NtcA enables
      a more differentiated response to nitrogen limitation and can be advantageous in
      native habitats of Synechocystis.

PMID- 29036483
TI  - A Decade of War: Prospective Trajectories of Posttraumatic Stress Disorder
      Symptoms Among Deployed US Military Personnel and the Influence of Combat
      Exposure.
AB  - Posttraumatic stress disorder (PTSD) is a common psychiatric disorder among
      service members and veterans. The clinical course of PTSD varies between
      individuals, and patterns of symptom development have yet to be clearly
      delineated. Previous studies have been limited by convenience sampling, short
      follow-up periods, and the inability to account for combat-related trauma. To
      determine the trajectories of PTSD symptoms among deployed military personnel
      with and without combat exposure, we used data from a population-based
      representative sample of 8,178 US service members who participated in the
      Millennium Cohort Study from 2001 to 2011. Using latent growth mixture modeling,
      trajectories of PTSD symptoms were determined in the total sample, as well as in
      individuals with and without combat exposure, respectively. Overall, 4
      trajectories of PTSD were characterized: resilient, pre-existing, new-onset, and
      moderate stable. Across all trajectories, combat-deployed service members
      diverged from non-combat-deployed service members, even after a single
      deployment. The former also generally had higher PTSD symptoms. Based on the
      models, nearly 90% of those without combat exposure remained resilient over the
      10-year period, compared with 80% of those with combat exposure. Findings
      demonstrate that although the clinical course of PTSD symptoms shows
      heterogeneous patterns of development, combat exposure is uniformly associated
      with poor mental health.

PMID- 29036484
TI  - Sex Differences in the Association of Diabetes With Cardiovascular Disease
      Outcomes Among African-American and White Participants in the Atherosclerosis
      Risk in Communities Study.
AB  - A sex * diabetes interaction in cardiovascular disease (CVD) has been established
      among white persons; however, it is unknown whether this interaction occurs among
      African Americans. We hypothesized that there was a multiplicative sex * diabetes
      interaction for CVD among African Americans participating in the Atherosclerosis
      Risk in Communities Study (1987-2013). Race-specific Cox models were run in three
      stages: Stage 1 examined baseline diabetes status; stage 2 examined baseline
      diabetes status with the competing risk of non-CVD death; and stage 3 examined
      time-varying diabetes status with a competing risk of non-CVD death. There were
      1,073 incident CVD events among 3,767 African Americans and 2,475 among 10,291
      white persons. Among African Americans, in stage 1 analysis, the hazard ratio for
      women with diabetes was 2.3 (95% confidence interval (CI): 2.0, 2.7) compared
      with women without diabetes after adjustment for age, and the corresponding
      hazard ratio for men was 1.8 (95% CI: 1.5, 2.1) (P for interaction = 0.014).
      After full adjustment, the diabetes hazard ratio was attenuated to 2.0 (95% CI:
      1.8, 2.3) among women and remained 1.8 (95% CI: 1.5, 2.1) for men (P for
      interaction = 0.058). A synergistic influence on CVD risk between being a black
      woman and having diabetes was consistent across stage 2 and stage 3 analyses,
      with marginally significant interaction, mirroring sex differences seen in
      whites.

PMID- 29036485
TI  - Economic Conditions During Pregnancy and Adverse Birth Outcomes Among Singleton
      Live Births in the United States, 1990-2013.
AB  - We know little about the relationship between the macroeconomy and birth
      outcomes, in part due to the methodological challenge of distinguishing effects
      of economic conditions on fetal health from effects of economic conditions on
      selection into live birth. We examined associations between state-level
      unemployment rates in the first 2 trimesters of pregnancy and adverse birth
      outcomes, using natality data on singleton live births in the United States
      during 1990-2013. We used fixed-effect logistic regression models and accounted
      for selection by adjusting for state-level unemployment before conception and
      maternal characteristics associated with both selection and birth outcomes. We
      also tested whether associations between macroeconomic conditions and birth
      outcomes differed during and after (compared with before) the Great Recession
      (2007-2009). Each 1-percentage-point increase in the first-trimester unemployment
      rate was associated with a 5% increase in odds of preterm birth, while second
      trimester unemployment was associated with a 3% decrease in preterm birth odds.
      During the Great Recession, however, first-trimester unemployment was associated
      with a 16% increase in odds of preterm birth. These findings increase our
      understanding of the effects of the Great Recession on health and add to growing
      literature suggesting that macro-level social and economic factors contribute to
      perinatal health.

PMID- 29036486
TI  - COMPARISON OF PADC NEUTRON DETECTORS FROM DIFFERENT SUPPLIERS.
AB  - The objective of this study was to compare poly-allyl diglycol carbonate (PADC)
      track detectors from different suppliers for linear energy transfer (LET)
      spectrometry and neutron dosimetry. PADCs are commonly used for passive personal
      neutron dosimetry, where a common approach is to couple the PADC with a plastic
      radiator to generate secondary charged particles. The neutron dose can be
      estimated using the track density or the average LET of the secondary particles.
      The characterisation of PADC in terms of LET spectrometric capability and neutron
      sensitivity was previously performed using PADC from Intercast S.r.l., Parma,
      Italy, but this company stopped the production. Since it is common experience
      that material from different suppliers can have different properties, it became
      necessary to perform a comparison of PADCs from different suppliers with the
      Intercast material. The study permits to compare the reading procedures used at
      Politecnico di Milano and at the Paul Scherrer Institute.

PMID- 29036487
TI  - Prospective and Retrospective Evaluation of the Performance of the FDA-Approved
      Cepheid Xpert Flu/RSV XC Assay.
AB  - Rapid and accurate detection of respiratory viruses is important in patient care
      and in guiding therapy and infection prevention policy. Rapid viral antigen
      assays are simple to perform and provide results within 15 to 30 minutes but are
      limited by their modest-to-moderate sensitivity. Molecular assays are more
      sensitive and specific but require more technical time and expertise and are more
      expensive. We verified the performance of the Xpert Flu/RSV XC assay
      prospectively, using patient respiratory samples from the 2014-2015 respiratory
      season, and, retrospectively, with frozen patient samples from the previous
      respiratory season. A total of 60 specimens were assayed on the Xpert Flu/RSV XC
      assay and by the GenMark Diagnostics eSensor Respiratory Viral Panel. The
      sensitivity of the Xpert Flu/RSV XC for Flu A was 100% (23/23), for Flu B, 80%
      (8/10), and for respiratory syncytial virus (RSV), 94.1% (16/17), compared to the
      reference assay (GenMark). The specificity was 100%. Eight specimens were
      positive for viruses other than Flu A/B or RSV, and this did not interfere with
      detection of targets in the Xpert assay. We demonstrated that the performance of
      the Xpert Flu/RSV XC was comparable to the more comprehensive molecular
      respiratory assay.

PMID- 29036488
TI  - Morphological, Physiological and Ultrastructural Changes in Flowers Explain the
      Spatio-Temporal Emission of Scent Volatiles in Polianthes tuberosa L.
AB  - Tuberose or Polianthes tuberosa L. is a horticultural crop of tropical origin,
      widely cultivated for its pleasant and intense floral fragrance in the evening.
      Here an investigation was made into the physiological and cell biological aspects
      of floral scent biosynthesis, tissue localization and emission that have not
      previously been examined. Volatiles collected from floral headspace were analyzed
      by gas chromatography-mass spectrometry (GC-MS) for identification of individual
      compounds and elucidation of emission patterns. Transcript accumulation and the
      amount of active enzyme were measured to understand the enzymatic route of scent
      volatile biosynthesis. Localization of scent volatiles was investigated by
      histochemical and ultrastructural studies. Scent emission was found to be
      rhythmic and nocturnal under normal day-night influence, peaking at night.
      Enhanced enzyme activities and transcript accumulation were recorded just prior
      to maximum emission. Through scanning electron microscopy (SEM) analysis, the
      presence of a large number of floral stomata on the adaxial surface of the tepal
      was revealed which might have bearing on tissue-specific emission. Guard cells of
      stomata responded significantly to histochemical tests, which also indicated that
      epidermal tissues are mostly involved in scent emission. High metabolic activity
      was found in epidermal layers during anthesis as shown by transmission electron
      microscopy (TEM) analysis. Further, new insight into the localization of scent
      compounds, the plausible tissue involved in their release along with the
      preceding ultrastructural changes at the cellular levels is presented. Finally,
      ultrastructural analysis of the tepal surface has been able to fill a major gap
      in knowledge of stomatal involvement during scent emission.

PMID- 29036489
TI  - Training Community Health Workers to promote breast cancer screening in Brazil.
AB  - Although it has been show that early detection through mammograms is the most
      effective way to reduce breast cancer mortality, breast cancer is the leading
      cause of cancer deaths among women worldwide with survival rates being even lower
      in low- and middle-income countries as compared to high-income countries. Despite
      the availability of breast cancer screening programs in Brazil through the public
      health system, some women do not participate in these programs due to structural
      and/or inter/intrapersonal barriers. The Community Health Worker (CHW) model is a
      promising approach to reach these women who have not been reached through other
      efforts. This paper describes a participatory approach for capacity building of
      CHWs to promote breast cancer screening among low-income women 50 years of age
      and older in a southern city in Brazil as a combined effort between two academic
      institutions, the municipal health care system, and a local non-profit
      organization. The capacity building program consisted of an 8-hour training
      focusing on knowledge (e.g., breast cancer and screening) and skills (e.g.,
      communication skills, basic principles of behavior change) to promote breast
      cancer screening among community members. Pre- and post-test questionnaires
      assessed changes in breast cancer knowledge and self-perceived knowledge and
      confidence (N=44). There was a significant increase in objective knowledge
      regarding breast cancer overall, risk factors, and behavior change strategies
      between pre- and post-test. There was also a significant increase in self
      perceived knowledge and confidence, items related to knowledge about breast
      cancer, breast cancer early detection methods, and the ability to solve problems
      between pre- and post-test as well as a significant increase in their confidence
      to motivate women to get a mammogram. Overall, this study demonstrates the
      importance of welldeveloped capacity building programs to promote breast cancer
      screening among health care professionals, especially those with limited
      educational attainment, such as CHWs.

PMID- 29036490
TI  - Optimizing DNA assembly based on statistical language modelling.
AB  - By successively assembling genetic parts such as BioBrick according to
      grammatical models, complex genetic constructs composed of dozens of functional
      blocks can be built. However, usually every category of genetic parts includes a
      few or many parts. With increasing quantity of genetic parts, the process of
      assembling more than a few sets of these parts can be expensive, time consuming
      and error prone. At the last step of assembling it is somewhat difficult to
      decide which part should be selected. Based on statistical language model, which
      is a probability distribution P(s) over strings S that attempts to reflect how
      frequently a string S occurs as a sentence, the most commonly used parts will be
      selected. Then, a dynamic programming algorithm was designed to figure out the
      solution of maximum probability. The algorithm optimizes the results of a genetic
      design based on a grammatical model and finds an optimal solution. In this way,
      redundant operations can be reduced and the time and cost required for conducting
      biological experiments can be minimized.

PMID- 29036491
TI  - Transcription-Associated Compositional Skews in Drosophila Genes.
AB  - In many organisms, local deviations from Chargaff's second parity rule are
      observed around replication and transcription start sites and within intron
      sequences. Here, we use expression data as well as a whole-genome data set of
      nearly 200 haplotypes to investigate such compositional skews in Drosophila
      melanogaster genes. We find a positive correlation between compositional skew and
      gene expression, comparable in strength to similar correlations between
      expression levels and genome-wide sequence features. This correlation is
      relatively stronger for germline, compared with somatic expression, consistent
      with the process of transcription-associated mutation bias. We also inferred
      mutation rates from alleles segregating at low frequencies in short introns, and
      show that, whereas the overall GC content of short introns does not conform to
      the equilibrium expectation, the level of the observed deviation from the second
      parity rule is generally consistent with the inferred rates.

PMID- 29036492
TI  - Partners' Overestimation of Patients' Pain Severity: Relationships with Partners'
      Interpersonal Responses.
AB  - Objectives: The present study examined whether concordance between patients' and
      their partners' reports of patient pain severity relates to partners' social
      support and behavioral responses in couples coping with chronic pain. Methods:
      Fifty-two couples completed questionnaires about the patient's pain severity.
      Both dyad members also rated the partner's social support and negative,
      solicitous, and distracting responses toward the patient when in pain. Results:
      Bivariate correlations showed moderate correspondence between patient and partner
      ratings of pain severity (r = 0.55) and negative (r = 0.46), solicitous (r =
      0.47), and distracting responses (r = 0.53), but lower correspondence for social
      support (r = 0.28). Twenty-eight couples (54%) were concordant in their
      perceptions of patient pain; partners overestimated pain in 14 couples (27%), and
      partners underestimated pain in 10 couples (19%). Couple concordance in pain
      perceptions was not related to patients' reports; however, it significantly
      predicted partners' reports: Partners who overestimated pain reported giving more
      social support (beta = 0.383, P = 0.016), fewer negative responses (beta = 
      0.332, P = 0.029), and more solicitous responses (beta = 0.438, P = 0.016) than
      partners who were in agreement or who underestimated pain. Discussion: Partner
      overestimation of pain severity is associated with partner-reported but not with
      patient-reported support-related responses. This finding has important clinical
      implications for couple interventions in chronic pain.

PMID- 29036493
TI  - Predicting Remission in Subjects at Clinical High Risk for Psychosis Using
      Mismatch Negativity.
AB  - Background: The declining transition rate to psychotic disorder and the
      increasing rate of nonpsychotic poor outcomes among subjects at clinical high
      risk (CHR) for psychosis have increased the need for biomarkers to predict
      remission regardless of transition. This study investigated whether mismatch
      negativity (MMN) predicts the prognosis of CHR individuals during a 6-year follow
      up period. Methods: A total of 47 healthy control (HC) subjects and 48 subjects
      at CHR for psychosis participated in the MMN assessment. The clinical statuses of
      the CHR subjects were examined at baseline and regularly for up to 6 years. The
      CHR subjects were divided into remitter and nonremitter groups, and the baseline
      MMN amplitudes and latencies were compared across the remitter, nonremitter, and
      HC groups. Regression analyses were performed to identify the predictive factors
      of remission, the improvement of attenuated positive symptoms, and functional
      recovery. Results: CHR nonremitters showed reduced MMN amplitudes at baseline
      compared to CHR remitters and HC subjects. A logistic regression analysis
      revealed that the baseline MMN amplitude at the frontal electrode site was the
      only significant predictor of remission. In a multiple regression analysis, the
      MMN amplitude, antipsychotic use, and years of education predicted an improvement
      in attenuated positive symptoms. The MMN amplitude at baseline predicted
      functional recovery. Conclusions: These results suggest that MMN is a putative
      predictor of prognosis regardless of the transition to psychotic disorder in
      subjects at CHR. Early prognosis prediction and the provision of appropriate
      interventions based on the initial CHR status might be aided using MMN.

PMID- 29036494
TI  - Transcriptional accuracy modeling suggests two-step proofreading by RNA
      polymerase.
AB  - We suggest a novel two-step proofreading mechanism with two sequential rounds of
      proofreading selection in mRNA transcription. It is based on the previous
      experimental observations that the proofreading RNA polymerase cleaves off
      transcript fragments of at least 2 nt and that transcript elongation after a
      nucleotide misincorporation is anomalously slow. Taking these results into
      account, we extend the description of the accuracy of template guided nucleotide
      selection beyond previous models of RNA polymerase-dependent DNA transcription.
      The model derives the accuracy of initial and proofreading base selection from
      experimentally estimated nearest-neighbor parameters. It is also used to estimate
      the small accuracy enhancement of polymerase revisiting of previous positions
      following transcript cleavage.

PMID- 29036495
TI  - The p16/miR-217/EGR1 pathway modulates age-related tenogenic differentiation in
      tendon stem/progenitor cells.
AB  - Previous studies have shown that the differentiation potential declines with the
      age of progenitor cells and is linked to altered levels of senescence markers.
      The purpose of this study was to test whether senescence marker p16 affects age
      related tenogenic differentiation in tendon stem/progenitor cells (TSPCs). Young
      and aged TSPCs were isolated from young/healthy and aged/degenerated human
      Achilles tendons, respectively. Cellular aging and capacity for tenogenic
      differentiation were examined. The results showed that the tenogenic
      differentiation capacity of TSPCs significantly decreases with advancing age.
      TSPCs from elderly donors showed upregulation of senescence-associated beta
      galactosidase and p16 and concurrently a decrease in Type I collagen
      concentration and in the expressions of tendon-related markers: Scx, Tnmd, Bgn,
      Dcn, Col1, and Col3. Overexpression of p16 significantly inhibited tenogenic
      differentiation of young TSPCs. Analysis of the mechanism revealed that this
      effect is mediated by microRNA-217 and its target EGR1. These results indicated
      that p16 inhibits tenogenic differentiation of TSPCs via microRNA signaling
      pathways, which may serve as a potential target for the prevention or treatment
      in the future.

PMID- 29036496
TI  - COMPARISON OF MEASURES ON PROTECTION AGAINST ACCIDENTAL RADIATION AND INDOOR
      RADON EXPOSURE IN MUSLYUMOVO, TECHA RIVER.
AB  - The objective of the study was comparison of the doses received due to
      contamination of the Techa River with those received from the indoor radon
      exposure. The study was performed on the example of Muslyumovo, the village
      closest to Mayak nuclear complex. The accidental doses were estimated using data
      on radionuclide intakes and ICRP-72 dose coefficients, and Techa River Dosimetry
      System. Radon exposure was estimated applying results of the radon surveys in
      1992 and 2015. The doses prevented by means of different protection measures were
      considered. The maximum reduction of population exposure could be achieved in the
      case of timely evacuation to uncontaminated territory together with the indoor
      radon prevention measures.

PMID- 29036498
TI  - British Widows of the South African War and the Origins of War Widows' Pensions.
AB  - The South African War of 1899-1902 cost the lives of 22,000 British and colonial
      soldiers and created almost 5,000 British war widows. It was in this context that
      the first state pensions for the widows of rank and file soldiers were introduced
      in 1901. Triggered by unexpectedly high casualty rates and widespread
      dissatisfaction with charitable provision, the introduction of state pensions
      also reflected changing public attitudes towards soldiers and their dependants in
      the context of an imperial war. Dismissed in the historiography as insignificant
      because of its low rates and restrictive eligibility clauses, the 1901 scheme in
      fact delivered pensions to the majority of war widows and made the Edwardian
      state their most important source of financial support. This article, after
      discussing the social and political context in which widows' pensions were
      developed, analyses the economics of the scheme and how key eligibility rules
      were formulated, before investigating significant changes in the scheme to 1920,
      the point at which Boer War widows were finally granted full maintenance.
      Strongly influenced by the practices of Victorian armed forces charities and by
      contemporary ideologies of gender and class, the South African War pension
      regulations created precedents which would continue to shape pensions for
      military widows to the end of the twentieth century.

PMID- 29036497
TI  - Forecasting residue-residue contact prediction accuracy.
AB  - Motivation: Apart from meta-predictors, most of today's methods for residue
      residue contact prediction are based entirely on Direct Coupling Analysis (DCA)
      of correlated mutations in multiple sequence alignments (MSAs). These methods are
      on average ~40% correct for the 100 strongest predicted contacts in each protein.
      The end-user who works on a single protein of interest will not know if
      predictions are either much more or much less correct than 40%, which is
      especially a problem if contacts are predicted to steer experimental research on
      that protein. Results: We designed a regression model that forecasts the accuracy
      of residue-residue contact prediction for individual proteins with an average
      error of 7 percentage points. Contacts were predicted with two DCA methods
      (gplmDCA and PSICOV). The models were built on parameters that describe the MSA,
      the predicted secondary structure, the predicted solvent accessibility and the
      contact prediction scores for the target protein. Results show that our models
      can be also applied to the meta-methods, which was tested on RaptorX.
      Availability and implementation: All data and scripts are available from
      http://comprec-lin.iiar.pwr.edu.pl/dcaQ/. Contact:
      malgorzata.kotulska@pwr.edu.pl. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29036499
TI  - VCF-Explorer: filtering and analysing whole genome VCF files.
AB  - Summary: The decreasing cost in high-throughput technologies led to a number of
      sequencing projects consisting of thousands of whole genomes. The paradigm shift
      from exome to whole genome brings a significant increase in the size of output
      files. Most of the existing tools which are developed to analyse exome files are
      not adequate for larger VCF files produced by whole genome studies. In this work
      we present VCF-Explorer, a variant analysis software capable of handling large
      files. Memory efficiency and avoiding computationally costly pre-processing step
      enable to carry out the analysis to be performed with ordinary computers. VCF
      Explorer provides an easy to use environment where users can define various types
      of queries based on variant and sample genotype level annotations. VCF-Explorer
      can be run in different environments and computational platforms ranging from a
      standard laptop to a high performance server. Availability and implementation:
      VCF-Explorer is freely available at: http://vcfexplorer.sourceforge.net/.
      Contact: mete.akgun@tubitak.gov.tr. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 29036501
TI  - MULTI-YEAR MONITORING OF RADON IN BOREHOLES AT THE MODRA GEOPHYSICAL OBSERVATORY,
      SLOVAKIA.
AB  - Long-term radon monitoring was performed in two boreholes, at a depth of 13 m in
      the 40 m deep V-2 borehole (August 2003-September 2005), and at 3 m depth in the
      10 m deep V-3 borehole (August 2003-April 2008). Diurnal, multi-day and annual
      variations in radon time-series were observed. Daily average of radon activity in
      V-2 borehole was significantly higher and ranged from 6.5 to 383.7 kBq/m3, while
      in V-3 borehole only between 1.2 and 139.4 kBq/m3. The seasonal pattern was more
      pronounced in V-3 time series, with the maximum occurring from October to March.
      Multi-day variations (2-10 days) were registered in V-2 and V-3 mostly
      simultaneously, with higher discrepancy in spring and summer periods, when radon
      activity in V-3 borehole was low. Diurnal radon variations with two maxima and
      two minima per day were registered in both boreholes. The influence of
      meteorological parameters on radon concentrations was investigated. The overall
      impression is that seasonal variation in radon in V-3 borehole seems to be
      connected with the temperature variation. Multi-day variations of radon in both
      boreholes coincided with the atmospheric pressure changes. An increase in radon
      activity was observed in V-3 borehole after the rainfall in spring and summer
      seasons.

PMID- 29036500
TI  - Glioma CpG island methylator phenotype (G-CIMP): biological and clinical
      implications.
AB  - Gliomas are a heterogeneous group of brain tumors with distinct biological and
      clinical properties. Despite advances in surgical techniques and clinical
      regimens, treatment of high-grade glioma remains challenging and carries dismal
      rates of therapeutic success and overall survival. Challenges include the
      molecular complexity of gliomas, as well as inconsistencies in histopathological
      grading, resulting in an inaccurate prediction of disease progression and failure
      in the use of standard therapy. The updated 2016 World Health Organization (WHO)
      classification of tumors of the central nervous system reflects a refinement of
      tumor diagnostics by integrating the genotypic and phenotypic features, thereby
      narrowing the defined subgroups. The new classification recommends molecular
      diagnosis of isocitrate dehydrogenase (IDH) mutational status in gliomas. IDH
      mutant gliomas manifest the cytosine-phosphate-guanine (CpG) island methylator
      phenotype (G-CIMP). Notably, the recent identification of clinically relevant
      subsets of G-CIMP tumors (G-CIMP-high and G-CIMP-low) provides a further
      refinement in glioma classification that is independent of grade and histology.
      This scheme may be useful for predicting patient outcome and may be translated
      into effective therapeutic strategies tailored to each patient. In this review,
      we highlight the evolution of our understanding of the G-CIMP subsets and how
      recent advances in characterizing the genome and epigenome of gliomas may
      influence future basic and translational research.

PMID- 29036502
TI  - Three Cases of Fatal Acrylfentanyl Toxicity in the United States and a Review of
      Literature.
AB  - Fentanyl analogs pose a unique challenge for forensic pathologists and
      toxicologists. The extreme potency of these analogs results in minute blood,
      urine and vitreous concentrations that are technically difficult to identify.
      This in addition to their absence from standard drug screening may potentiate a
      setting of apparent drug overdose without an immediately identifiable source. The
      following case series illustrates three such encounters with acrylfentanyl, an
      analog whose presence has not yet been reported in the scientific literature in
      the United States. In case 1, a 23-year-old male with a history of heroin abuse
      was found unresponsive in a field several feet away from his parked vehicle.
      Drugs and paraphernalia recovered from the vehicle tested positive for
      methamphetamine and acrylfentanyl. Directed toxicology was requested, revealing
      acrylfentanyl concentrations of 0.3 ng/mL. In case 2, a 43-year-old male with a
      history of heroin abuse was found unresponsive in his home after allegedly
      injecting what he thought to be heroin. Directed toxicology revealed an
      acrylfentanyl concentration of 0.95 ng/mL in peripheral blood. In case 3, a 26
      year-old male with a history of heroin abuse use found unresponsive on the
      bathroom floor of a grocery store. Drug paraphernalia and a plastic baggy with
      residue were present. Directed analysis of peripheral blood for fentanyl analogs
      revealed acrylfentanyl and furanylfentanyl at concentrations of 0.32 and 0.95
      ng/mL, respectively. In all three cases, the initial comprehensive blood
      toxicology did not reveal the presence of acrylfentanyl, highlighting the need
      for directed testing when scene findings and history suggest a possible substance
      outside the scope of traditional screening.

PMID- 29036503
TI  - Implementing electronic health records (EHRs): health care provider perceptions
      before and after transition from a local basic EHR to a commercial comprehensive
      EHR.
AB  - Objective: We assessed changes in the percentage of providers with positive
      perceptions of electronic health record (EHR) benefit before and after transition
      from a local basic to a commercial comprehensive EHR. Methods: Changes in the
      percentage of providers with positive perceptions of EHR benefit were captured
      via a survey of academic health care providers before (baseline) and at 6-12
      months (short term) and 12-24 months (long term) after the transition. We
      analyzed 32 items for the overall group and by practice setting, provider age,
      and specialty using separate multivariable-adjusted random effects logistic
      regression models. Results: A total of 223 providers completed all 3 surveys (30%
      response rate): 85.6% had outpatient practices, 56.5% were >45 years old, and
      23.8% were primary care providers. The percentage of providers with positive
      perceptions significantly increased from baseline to long-term follow-up for
      patient communication, hospital transitions - access to clinical information,
      preventive care delivery, preventive care prompt, preventive lab prompt,
      satisfaction with system reliability, and sharing medical information (P < .05
      for each). The percentage of providers with positive perceptions significantly
      decreased over time for overall satisfaction, productivity, better patient care,
      clinical decision quality, easy access to patient information, monitoring
      patients, more time for patients, coordination of care, computer access, adequate
      resources, and satisfaction with ease of use (P < 0.05 for each). Results varied
      by subgroup. Conclusion: After a transition to a commercial comprehensive EHR,
      items with significant increases and significant decreases in the percentage of
      providers with positive perceptions of EHR benefit were identified, overall and
      by subgroup.

PMID- 29036504
TI  - Echocardiographic Left Ventricular Reverse Remodeling After 18 Months of
      Antihypertensive Treatment in Stage I Hypertension. Results From the Prever
      Treatment Study.
AB  - BACKGROUND: Antihypertensive treatment improves echocardiographic parameters of
      hypertensive target organ damage in stage II hypertension, but less is known
      about the effects in stage I hypertension. METHODS: In a cohort study nested in
      the randomized double-blind trial PREVER-treatment, 2-dimensional echocardiograms
      were performed in 110 individuals, aged 54.8 +/- 7.9 years-old, with stage I
      hypertension at baseline and after 18 months of treatment with
      chlorthalidone/amiloride or losartan. RESULTS: At baseline, 66 (60%) participants
      had concentric remodeling. After antihypertensive treatment, systolic (SBP) and
      diastolic blood pressure (BP) were reduced from 141/90 to 130/83 mm Hg (P =
      0.009). There was a significant reduction in left ventricular (LV) mass (LVM)
      index (82.7 +/- 17.1 to 79.2 +/- 17.5 g/m2; P = 0.005) and relative wall
      thickness (0.45 +/- 0.06 to 0.42 +/- 0.05; P < 0.001), increasing the proportion
      of participants with normal LV geometry (31% to 49%, P = 0.006). Left atrial (LA)
      volume index reduced (26.8 +/- 7.3 to 24.9 +/- 6.5 ml/m2; P = 0.001), and mitral
      E-wave deceleration time increased (230 +/- 46 to 247 +/- 67 ms; P = 0.005), but
      there was no change in other parameters of diastolic function. LVM reduction was
      significantly higher in the 2 higher tertiles of SBP reduction compared to the
      lower tertile. CONCLUSIONS: Treatment of patients with stage I hypertension for
      18 months promotes favorable effects in the LA and LV remodeling. This
      improvement in cardiac end-organ damage might be associated with reduction of
      long term clinical consequences of hypertensive cardiomyopathy, particularly
      heart failure with preserved ejection fraction.

PMID- 29036505
TI  - Increased mortality in haemodialysis patients administered high doses of
      erythropoiesis-stimulating agents: a propensity score-matched analysis.
AB  - Background: Erythropoiesis-stimulating agents (ESAs) are widely used to treat
      anaemia in patients with chronic kidney disease. The issue of ESA safety has been
      raised in multiple studies, with correlates derived for elevated cancer incidence
      and mortality. Whether these associations are related to ESA dose or the typology
      of the patient remains obscure. Methods: A multicentre, observational
      retrospective propensity score-matched study was designed to analyse the effects
      of weekly ESA dose in 1679 incident haemodialysis (HD) patients. ESA
      administration was according to standard medical practice. Patients were grouped
      as quintiles, according to ESA dose, in order to compare mortality and
      hospitalization data. Using propensity score matching (PSM), we defined two
      groups of 324 patients receiving weekly threshold ESA doses of either > or <=8000
      IU. Results: Kaplan-Meier survival curves indicated significant increases in the
      risk of mortality in patients administered with high doses of ESAs (>8127.4
      IU/week). Multivariate Cox models identified a high ESA dose as an independent
      predictor for all-cause and cardiovascular (CV) mortality. Moreover, logistic
      regression models identified high ESA doses as an independent predictor for all
      cause, CV and infectious hospitalization. PSM analyses confirmed that weekly ESA
      doses of >8000 IU constitute an independent predictor of all-cause mortality and
      hospitalization, even though the adjusted cohort displayed the same demographic
      features, inflammatory profile, clinical HD parameters and haemoglobin levels.
      Conclusions: Our data suggest that ESA doses of >8000 IU/week are associated with
      an increased risk of all-cause mortality and hospitalization in HD patients.

PMID- 29036506
TI  - Bony changes in Primary Hyperparathyroidism.

PMID- 29036507
TI  - ggseqlogo: a versatile R package for drawing sequence logos.
AB  - Summary: Sequence logos have become a crucial visualization method for studying
      underlying sequence patterns in the genome. Despite this, there remains a
      scarcity of software packages that provide the versatility often required for
      such visualizations. ggseqlogo is an R package built on the ggplot2 package that
      aims to address this issue. ggseqlogo offers native illustration of publication
      ready DNA, RNA and protein sequence logos in a highly customizable fashion with
      features including multi-logo plots, qualitative and quantitative colour schemes,
      annotation of logos and integration with other plots. The package is intuitive to
      use and seamlessly integrates into R analysis pipelines. Availability and
      implementation: ggseqlogo is released under the GNU licence and is freely
      available via CRAN-The Comprehensive R Archive Network https://cran.r
      project.org/web/packages/ggseqlogo. A detailed tutorial can be found at
      https://omarwagih.github.io/ggseqlogo. Contact: wagih@ebi.ac.uk.

PMID- 29036508
TI  - A NOVEL TEPC FOR MICRODOSIMETRY AT NANOMETRIC LEVEL: RESPONSE AGAINST DIFFERENT
      NEUTRON FIELDS.
AB  - Tissue equivalent proportional counter (TEPC) is the most accurate device for
      measuring the microdosimetric properties of a particle beam, nevertheless no
      detailed information on the track structure of the impinging particles can be
      obtained, since the lower operation limit of common TEPCs is ~0.3 MUm. On the
      other hand, the pattern of particle interactions at the nanometer level is
      measured by only three different nanodosimeters worldwide: practical instruments
      are not yet available. In order to partially fill the gap between microdosimetry
      and track-nanodosimetry, a low-pressure avalanche-confinement TEPC was recently
      designed and constructed for simulating tissue-equivalent sites down to the
      nanometric region. The present article aims at describing the response of this
      newly developed TEPC in the range 0.3 MUm-25 nm against a fast neutron field from
      a 241Am-Be source and a quasi-monoenergetic neutron beam. The experimental
      results are in good agreement with Monte Carlo simulations carried out with the
      FLUKA code.

PMID- 29036509
TI  - Medication usage change in older people (65+) in England over 20 years: findings
      from CFAS I and CFAS II.
AB  - Background: medical practice has changed over the last decades reflecting the
      ageing population, when multi-morbidity requiring multiple medications is more
      common. Objective: describe and quantify self-reported medicine use including
      both prescription and over the counter medicines in two comparable population
      based studies of older people (65+) in England and to assess the nature and scale
      of polypharmacy. Methods: data used were from two separate population-based
      studies; the Cognitive Function Ageing Study I and II. Descriptive analyses were
      performed to summarise and quantify general medicine use. Negative binomial
      regression models were fitted to determine factors associated with the number of
      medicines used. Results: medication use, including both prescribed medicines and
      over the counter products has increased dramatically over the last 2 decades. The
      number of people taking five or more items quadrupled from 12 to 49%, while the
      proportion of people who did not take any medication has decreased from around 1
      in 5 to 1 in 13. Cardiovascular drugs were the most frequently taken medication.
      Polypharmacy is associated with increases in the number of diagnosed long-term
      conditions. Conclusions: comparison between CFAS I and II reveals marked
      increases in medication usage and polypharmacy in the older population. The
      influence of healthcare organisation, introduction of new guidelines and
      technology changes leading to diagnosis of earlier, milder chronic diseases and
      treatment may be contributing to this changing pattern. Further research is
      needed to develop practical solutions to optimise medication management in older
      people, reducing the harming associated with medication.

PMID- 29036510
TI  - Cancer mortality in residents of the terrain-shielded area exposed to fallout
      from the Nagasaki atomic bombing.
AB  - The health effects of radiation exposure from the atomic bomb fallout remain
      unclear. The objective of the present study is to elucidate the association
      between low-dose radiation exposure from the atomic bomb fallout and cancer
      mortality among Nagasaki atomic bomb survivors. Of 77 884 members in the Nagasaki
      University Atomic Bomb Survivors Cohort, 610 residents in the terrain-shielded
      area with fallout were selected for this analysis; 1443 residents in the terrain
      shielded area without fallout were selected as a control group; and 3194
      residents in the direct exposure area were also selected for study. Fifty-two
      deaths due to cancer in the terrain-shielded fallout area were observed during
      the follow-up period from 1 January 1970 to 31 December 2012. The hazard ratio
      for cancer mortality in the terrain-shielded fallout area was 0.90 (95%
      confidence interval: 0.65-1.24). No increase in the risk of cancer mortality was
      observed, probably because the dose of the radiation exposure was low for
      residents in the terrain-shielded fallout areas of the Nagasaki atomic bomb, and
      also because the number of study subjects was small.

PMID- 29036511
TI  - THE NATIONAL RADON ARCHIVE AS A USEFUL TOOL FOR DEVELOPING AND UPDATING THE
      NATIONAL RADON ACTION PLAN.
AB  - International recommendations and regulations require developing of National
      Radon Action Plans (NRAPs) to effectively manage the protection of workers and
      population from radon exposure. In Italy, a NRAP was published in 2002 and
      several activities have been carried out in this framework. Information and data
      regarding these and previous activities have been collected in a National Radon
      Archive (NRA). Activities carried out by institutionally involved institutes and
      agencies include several national and regional surveys, involving more than 50
      000 indoor environments (dwellings, schools and workplaces), and remedial actions
      performed in ~350 buildings, largely in schools. Data collected in the NRA
      allowed also to estimate that lung cancer deaths attributable to radon exposure
      in Italy are ~3400 per year. On-going developments of the Italian NRA finalized
      to effectively use it as tool for developing, monitoring and updating the NRAP
      are also described.

PMID- 29036512
TI  - Job resignation after cancer diagnosis among working survivors in Japan: timing,
      reasons and change of information needs over time.
AB  - Objective: Despite advances in work-related policies for cancer survivors,
      support systems for working survivors in healthcare settings in Japan remain
      underdeveloped. We aimed to reveal (i) the present situation of cancer survivors'
      job resignation, the timing of resignation, and reasons for resignation; (ii)
      healthcare providers' screening behaviors of cancer survivors' work-related
      difficulties and (iii) changes to cancer survivors' information/support needs
      over time since diagnosis. Methods: We conducted an anonymous, cross-sectional
      survey using a convenience sample of re-visiting outpatients at three cancer
      centers in Japan in 2015. The questionnaire covered participants' demographic and
      clinical characteristics, change to job status, timing of and reasons for job
      resignation, screening experience regarding work-related difficulties by
      healthcare providers, and information/support needs at four distinct timings (at
      diagnosis, between diagnosis and initial treatment, between initial treatment and
      return-to-work, and after return-to-work). The results of 950 participants were
      eligible for statistical analysis. Results: Only 23.5% of participants were
      screened about work-related issues by healthcare providers despite 21.3%
      participants reporting resigning at least once. Among participants who resigned,
      40.2% decided to do so before initial treatment began. Regarding reasons for
      resignation, self-regulating and pessimistic reasons were ranked highly.
      Respondents' work-related information and support needs were observed to change
      over time. While treatment-related information (schedule and cost) was ranked
      highly at diagnosis, the need for more individually tailored information and
      support on work increased after treatment began. Conclusions: This study provides
      important basic data for developing effective support systems for working
      survivors of cancer in hospital settings.

PMID- 29036513
TI  - ScanGEO: parallel mining of high-throughput gene expression data.
AB  - Summary: Current options to mine publicly available gene expression data
      deposited in NCBI's gene expression omnibus (GEO), such as the GEO web portal and
      related applications, are optimized to reanalyze a single study, or search for a
      single gene, and therefore require manual intervention to reanalyze multiple
      studies for user-specified gene sets. ScanGEO is a simple, user-friendly Shiny
      web application designed to identify differentially expressed genes across all
      GEO studies matching user-specified criteria, for a flexible set of genes,
      visualize results and provide summary statistics and other reports using a single
      command. Availability and implementation: The ScanGEO source code is written in R
      and implemented as a Shiny app that can be freely accessed at
      http://scangeo.dartmouth.edu/ScanGEO/. For users who would like to run a local
      instantiation of the app, the R source code is available under a GNU GPLv3
      license at https://github.com/StantonLabDartmouth/AppScanGEO. Contact:
      katja.koeppen@dartmouth.edu. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29036514
TI  - RADON IN WORKPLACES-CZECH APPROACH TO EU BSS IMPLEMENTATION.
AB  - The European Council Directive 2013/59/Euratom of December 2013 established inter
      alia the uniform basic safety standards for the health protection of individuals
      being subject to occupational exposure. In Article 54, a new obligation is
      introduced-to regulate radon exposure in workplaces. The EU Member States are
      obliged to set national reference value for radon in workplaces, delineate the
      areas where the regulation will be applied and determine the concerned types of
      workplaces. The presented article shows the Czech approach to implementation of
      this obligation in national legislation and the first design of regulator's
      control activities to set the obligation in practice.

PMID- 29036516
TI  - A two-stage approach of gene network analysis for high-dimensional heterogeneous
      data.
AB  - Gaussian graphical models have been widely used to construct gene regulatory
      networks from gene expression data. Most existing methods for Gaussian graphical
      models are designed to model homogeneous data, assuming a single Gaussian
      distribution. In practice, however, data may consist of gene expression studies
      with unknown confounding factors, such as study cohort, microarray platforms,
      experimental batches, which produce heterogeneous data, and hence lead to false
      positive edges or low detection power in resulting network, due to those unknown
      factors. To overcome this problem and improve the performance in constructing
      gene networks, we propose a two-stage approach to construct a gene network from
      heterogeneous data. The first stage is to perform a clustering analysis in order
      to assign samples to a few clusters where the samples in each cluster are
      approximately homogeneous, and the second stage is to conduct an integrative
      analysis of networks from each cluster. In particular, we first apply a model
      based clustering method using the singular value decomposition for high
      dimensional data, and then integrate the networks from each cluster using the
      integrative $?psi$-learning method. The proposed method is based on an equivalent
      measure of partial correlation coefficients in Gaussian graphical models, which
      is computed with a reduced conditional set and thus it is useful for high
      dimensional data. We compare the proposed two-stage learning approach with some
      existing methods in various simulation settings, and demonstrate the robustness
      of the proposed method. Finally, it is applied to integrate multiple gene
      expression studies of lung adenocarcinoma to identify potential therapeutic
      targets and treatment biomarkers.

PMID- 29036517
TI  - George et al. Respond to "Diabetes and Cardiovascular Disease".

PMID- 29036515
TI  - The JASMONATE ZIM-Domain Gene Family Mediates JA Signaling and Stress Response in
      Cotton.
AB  - JASMONATE ZIM-domain (JAZ) family proteins are involved in regulating diverse
      biological processes in plants. However, their functions have not been well
      characterized in cotton (Gossypium spp.). In the present study, 13, 15, 25 and 30
      JAZ genes were identified in Gossypium arboretum, Gossypium raimondii, Gossypium
      barbadense and Gossypium hirsutum, respectively, based on gene homology.
      Selection and variation analyses showed that the single nucleotide polymorphism
      (SNP) density of GhJAZ genes in wild species was much higher than that in
      domesticated species. Expression pattern analysis showed that all the GhJAZ genes
      are expressed in at least one tissue and respond to one or more stress factors,
      as well as being induced by some phytohormones. The co-expression network
      indicated that GhJAZ genes might mediate multiple stress response pathways. Yeast
      two-hybrid (Y2H) experiments showed extensive interactions among GhJAZ proteins,
      including homo- and heteromeric interactions. Overexpressing one member of the
      JAZ gene family, GhJAZ2 (Gh_D06G0810), significantly enhanced sensitivity to salt
      stress in transgenic cotton. Transcriptome analysis indicated that GhJAZ2
      regulates stress responses possibly by participating in alpha-linolenic acid
      metabolism and jasmonate signaling, and is involved in the repression of GhMYC2
      regulated by GhJAZ2. Our data provide important clues for further elucidating the
      functions of JAZ genes in cotton.

PMID- 29036518
TI  - Are Prothrombotic Mutations a Time-to-Event Risk Factor?
AB  - Background: Deep vein thrombosis (DVT) represents a common disorder involving
      genetic and acquired risk factors. It has been proposed that acquired risk
      factors are more important with aging than genetic factors, indicating different
      prevalence of prothrombotic mutations throughout the lifespan. Objective: To
      determine the role of the most frequent prothrombotic genetic risk factors
      (Factor V [FV] Leiden and Factor II [FII] G20210A mutations) in first-time DVT
      etiology in patients of different ages. Method: This retrospective study included
      701 patients living in Serbia with diagnosed DVT as a first-time thrombotic
      event. Results: Risk assessment for mutations as age-related markers showed no
      statistical difference (FV Leiden mutation-OR, 1.027; 95% confidence interval
      [CI], .87-1.22; P = .76 and FII G20210A mutation-OR, 0.940, 95% CI, .74-1.19; P =
      .61). Our results show similar mutation prevalence regardless of how old the
      patients were at the time of the first DVT occurrence. Conclusion: Our results
      indicate that these 2 mutations cannot be used as prognostic marker for time-to
      event first DVT in the Serbian population; however, further studies are required.

PMID- 29036521
TI  - An interview with Dr John Kerr (Jock) Findlay.

PMID- 29036519
TI  - Distress, Impairment and the Extended Psychosis Phenotype: A Network Analysis of
      Psychotic Experiences in an US General Population Sample.
AB  - It has been proposed that subclinical psychotic experiences (PEs) may causally
      impact on each other over time and engage with one another in patterns of mutual
      reinforcement and feedback. This subclinical network of experiences in turn may
      facilitate the onset of psychotic disorder. PEs, however, are not inherently
      distressing, nor do they inevitably lead to impairment. The question arises
      therefore, whether nondistressing PEs, distressing PEs, or both, meaningfully
      inform an extended psychosis phenotype. The current study first aimed to exploit
      valuable ordinal data that captured the absence, occurrence and associated
      impairment of PEs in the general population to construct a general population
      based severity network of PEs. The study then aimed to partition the available
      ordinal data into 2 sets of binary data to test whether an occurrence network
      comprised of PE data denoting absence (coded 0) and occurrence/impairment (coded
      1) was comparable to an impairment network comprised of binary PE data denoting
      absence/occurrence (coded 0) and impairment (coded 1). Networks were constructed
      using state-of-the-art regularized pairwise Markov Random Fields (PMRF). The
      severity network revealed strong interconnectivity between PEs and nodes denoting
      paranoia were among the most central in the network. The binary PMRF impairment
      network structure was similar to the occurrence network, however, the impairment
      network was characterized by significantly stronger PE interconnectivity. The
      findings may help researchers and clinicians to consider and determine how, when,
      and why an individual might transition from experiences that are nondistressing
      to experiences that are more commonly characteristic of psychosis symptomology in
      clinical settings.

PMID- 29036522
TI  - More Alcohol, More Liver Injury: Not Always True.
AB  - An animal model of alcoholic liver disease (ALD) that recapitulates human disease
      is an unmet need. An alcohol-preferring strain and WT mice were fed alcohol by
      different techniques and with different diet compositions. Interestingly, the
      greatest alcohol consumers did not develop the worst ALD. This editorial
      highlights how diet and the gut microbiome/metabolome may influence the
      development/severity of ALD.

PMID- 29036520
TI  - From the Cover: Lung-Specific Overexpression of Constitutively Active IKK2
      Induces Pulmonary and Systemic Inflammations but Not Hypothalamic Inflammation
      and Glucose Intolerance.
AB  - The lung is constantly exposed to ambient pollutants such as ambient fine
      particulate matter (PM2.5), making it one of the most frequent locations of
      inflammation in the body. Given the establishment of crucial role of inflammation
      in the pathogenesis of cardiometabolic diseases, pulmonary inflammation is thus
      widely believed to be an important risk factor for cardiometabolic diseases.
      However, the causality between them has not yet been well established. To
      determine if pulmonary inflammation is sufficient to cause adverse
      cardiometabolic effects, SFTPC-rtTA+/-tetO-cre+/-pROSA-inhibitor kappaB kinase
      2(IKK2)ca+/- (LungIKK2ca) and littermate SFTPC-rtTA+/-tetO-cre-/-pROSA-IKK2ca+/-
      wildtype (WT) mice were fed with doxycycline diet to induce constitutively active
      Ikk2 (Ikk2ca) overexpression in the lung and their pulmonary, systemic, adipose,
      and hypothalamic inflammations, vascular function, and glucose homeostasis were
      assessed. Feeding with doxycycline diet resulted in IKK2ca overexpression in the
      lungs of LungIKK2ca but not WT mice. This induction of IKK2ca was accompanied by
      marked pulmonary inflammation as evidenced by significant increases in
      bronchoalveolar lavage fluid leukocytes, pulmonary macrophage infiltration, and
      pulmonary mRNA expression of tumor necrosis factor alpha (Tnfalpha) and
      interleukin-6 (Il-6). This pulmonary inflammation due to lung-specific
      overexpression of IKK2ca was sufficient to increase circulating TNFalpha and IL-6
      levels, adipose expression of Tnfalpha and Il-6 mRNA, aortic endothelial
      dysfunction, and systemic insulin resistance. Unexpectedly, no significant
      alteration in hypothalamic expression of Tnfalpha and Il-6 mRNA and glucose
      intolerance were observed in these mice. Pulmonary inflammation is sufficient to
      induce systemic inflammation, endothelial dysfunction, and insulin resistance,
      but not hypothalamic inflammation and glucose intolerance.

PMID- 29036524
TI  - PHOTON SPECTRA IN NPL STANDARD RADIONUCLIDE NEUTRON FIELDS.
AB  - A HPGe detector has been used to measure the photon spectra from the majority of
      radionuclide neutron sources in use at NPL (252Cf, 241Am-Be, 241Am-Li, 241Am-B).
      The HPGe was characterised then modelled to produce a response matrix. The
      measured pulse height spectra were then unfolded to produce photon fluence
      spectra. Changes in the photon spectrum with time from a 252Cf source are
      evident. Spectra from a 2-year-old and 42-year-old 252Cf source are presented
      showing the change from a continuum to peaks from long-lived isotopes of Cf.
      Other radionuclide neutron source spectra are also presented and discussed. The
      new spectra were used to improve the photon to neutron dose equivalent ratios
      from some earlier work at NPL with GM tubes and EPDs.

PMID- 29036525
TI  - Circulating microRNAs in arrhythmogenic right ventricular cardiomyopathy with
      ventricular arrhythmia.
AB  - Aims: MicroRNAs (miRNAs) have been implicated in cardiac diseases. This study
      aimed to characterize the circulating miRNAs in patients with arrhythmogenic
      right ventricular cardiomyopathy (ARVC) and correlate the miRNAs with the
      clinical outcomes of ARVC. Methods and results: This study included 62 patients
      with ventricular arrhythmia (VA): 28 patients (45%) had definite ARVC, 11 (18%)
      had borderline or possible ARVC, and 23 (37%) had idiopathic ventricular
      tachycardia (VT). In addition, 33 age- and sex-matched healthy subjects were
      enrolled as normal control subjects. The expression of selected miRNAs was
      analysed in all study subjects. The clinical outcomes of patients with definite
      ARVC after catheter ablation were further investigated. On the basis of the miRNA
      polymerase chain reaction array, we selected 11 miRNAs for analysis of their
      expression in the plasma of all subjects. Definite ARVC patients had
      significantly higher expression of circulating miR-144-3p, 145-5p, 185-5p, and
      494 than the three other groups. Out of 25 definite ARVC patients who underwent
      radiofrequency catheter ablation, recurrent VA occurred in 8 patients (32%)
      during the follow-up period (45 +/- 20 months). Definite ARVC patients with
      recurrent VA had a higher level of circulating miR-494 than did those without
      recurrence. Receiver operating characteristic analysis showed miR-494 to be a
      predictive factor of recurrent VA (area under the curve: 0.832). Conclusion:
      Plasma levels of miR-144-3p, 145-5p, 185-5p, and 494 were significantly elevated
      in definite ARVC patients with VA. An increased plasma level of miR-494 was
      associated with the recurrence of VA after ablation in definite ARVC patients.

PMID- 29036526
TI  - DynaPho: a web platform for inferring the dynamics of time-series
      phosphoproteomics.
AB  - Summary: Large-scale phosphoproteomics studies have improved our understanding of
      dynamic cellular signaling, but the downstream analysis of phosphoproteomics data
      is still a bottleneck. We develop DynaPho, a useful web-based tool providing
      comprehensive and in-depth analyses of time-course phosphoproteomics data, making
      analysis intuitive and accessible to non-bioinformatics experts. The tool
      currently implements five analytic modules, which reveal the transition of
      biological pathways, kinase activity, dynamics of interaction networks and the
      predicted kinase-substrate associations. These features can assist users in
      translating their larger-scale time-course phosphoproteomics data into valuable
      biological discoveries. Availability and implementation: DynaPho is freely
      available at http://dynapho.jhlab.tw/ . Contact: hsuancheng@ym.edu.tw or
      yukijuan@ntu.edu.tw . Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29036523
TI  - Stress-Dependent Association Between Polygenic Risk for Schizophrenia and
      Schizotypal Traits in Young Army Recruits.
AB  - Schizotypal personality traits may increase proneness to psychosis and likely
      index familial vulnerability to schizophrenia (SZ), implying shared genetic
      determinants with SZ. Here, we sought to investigate the contribution of common
      genetic risk variation for SZ on self-reported schizotypy in 2 ethnically
      homogeneous cohorts of healthy young males during compulsory military service,
      enrolled in the Athens Study of Proneness and Incidence of Schizophrenia (ASPIS,
      N = 875) and the Learning on Genetics of Schizophrenia Spectrum study (LOGOS, N =
      690). A follow-up psychometric assessment was performed in a sub-sample of the
      ASPIS (N = 121), 18 months later at military service completion. Polygenic risk
      scores (PRS) for SZ were derived based on genome-wide association meta-analysis
      results from the Psychiatric Genomics Consortium. In the ASPIS, higher PRSSZ
      significantly associated with lower levels of positive (ie, perceptual
      distortions), disorganization and paranoid facets of schizotypy, whereas no
      association with negative (ie, interpersonal) facets was noted. Importantly,
      longitudinal data analysis in the ASPIS subsample revealed that PRSSZ was
      inversely associated with positive schizotypy at military induction (stressed
      condition) but not at follow-up (nonstressed condition), providing evidence for
      environmental rather than SZ-implicated genetic influences. Moreover, consistent
      with prior reports, PRSSZ was positively correlated with trait anxiety in the
      LOGOS and additionally the recruits with higher PRSSZ and trait anxiety exhibited
      attenuated paranoid ideation. Together, these findings do not support an
      etiological link between increased polygenic liability for SZ and schizotypy,
      suggesting that psychosocial stress or trait anxiety may impact schizotypal
      phenotypic expressions among healthy young adults not genetically predisposed to
      SZ.

PMID- 29036527
TI  - iSyTE 2.0: a database for expression-based gene discovery in the eye.
AB  - Although successful in identifying new cataract-linked genes, the previous
      version of the database iSyTE (integrated Systems Tool for Eye gene discovery)
      was based on expression information on just three mouse lens stages and was
      functionally limited to visualization by only UCSC-Genome Browser tracks. To
      increase its efficacy, here we provide an enhanced iSyTE version 2.0 (URL:
      http://research.bioinformatics.udel.edu/iSyTE) based on well-curated,
      comprehensive genome-level lens expression data as a one-stop portal for the
      effective visualization and analysis of candidate genes in lens development and
      disease. iSyTE 2.0 includes all publicly available lens Affymetrix and Illumina
      microarray datasets representing a broad range of embryonic and postnatal stages
      from wild-type and specific gene-perturbation mouse mutants with eye defects.
      Further, we developed a new user-friendly web interface for direct access and
      cogent visualization of the curated expression data, which supports convenient
      searches and a range of downstream analyses. The utility of these new iSyTE 2.0
      features is illustrated through examples of established genes associated with
      lens development and pathobiology, which serve as tutorials for its application
      by the end-user. iSyTE 2.0 will facilitate the prioritization of eye development
      and disease-linked candidate genes in studies involving transcriptomics or next
      generation sequencing data, linkage analysis and GWAS approaches.

PMID- 29036528
TI  - Prediction of pathologic responders to neoadjuvant chemoradiotherapy by diffusion
      weighted magnetic resonance imaging in locally advanced esophageal squamous cell
      carcinoma: a prospective study.
AB  - This study aims to investigate the role of diffusion-weighted magnetic resonance
      imaging (DW-MRI) in ESCC patients receiving neoadjuvant concurrent
      chemoradiotherapy (CCRT), and the efficacy of apparent diffusion coefficient
      (ADC) values in predicting pathologic response to neoadjuvant CCRT. Twenty-eight
      locally advanced ESCC patients treated with neoadjuvant CCRT followed by radical
      resection were prospectively enrolled. DW-MRI was recommended to be performed
      within 2 weeks before and 4-6 weeks after neoadjuvant CCRT. The calculated ADCs
      pre- (ADC1) and post- (ADC2) neoadjuvant CCRT, the definite (DeltaADC) and
      percentage changes (DeltaADC%) were analyzed for the efficacy of predicting
      pathologic response to neoadjuvant CCRT. Twenty patients had been identified as
      responders (tumor regression grade 1-2). Among them, ADC2 (3.02 +/- 0.84 vs. 2.12
      +/- 0.44 * 10-3 mm2/s, P = 0.001) and DeltaADC (1.22 +/- 0.78 vs 0.64 +/- 0.26 *
      10-3 mm2/s, P = 0.007) were significantly higher than those of nonresponders
      (tumor regression grade: 3-5). Receiver operating characteristic analysis
      revealed that ADC2 exhibited an overall accuracy of in 71.4% in predicting
      pathologic response, with a sensitivity of 60.0%, a specificity of 100%, a
      positive predictive value of 100%, and a negative predictive value of 50.0%, when
      3.04 * 10-3 mm2/s was used as the cutoff value. ADC value could be useful in
      predicting pathologic response to neoadjuvant CCRT in ESCC patients. High
      postneoadjuvant CCRT ADC is a predictive indicator for good response.

PMID- 29036529
TI  - ITSoneDB: a comprehensive collection of eukaryotic ribosomal RNA Internal
      Transcribed Spacer 1 (ITS1) sequences.
AB  - A holistic understanding of environmental communities is the new challenge of
      metagenomics. Accordingly, the amplicon-based or metabarcoding approach, largely
      applied to investigate bacterial microbiomes, is moving to the eukaryotic world
      too. Indeed, the analysis of metabarcoding data may provide a comprehensive
      assessment of both bacterial and eukaryotic composition in a variety of
      environments, including human body. In this respect, whereas hypervariable
      regions of the 16S rRNA are the de facto standard barcode for bacteria, the
      Internal Transcribed Spacer 1 (ITS1) of ribosomal RNA gene cluster has shown a
      high potential in discriminating eukaryotes at deep taxonomic levels. As
      metabarcoding data analysis rely on the availability of a well-curated barcode
      reference resource, a comprehensive collection of ITS1 sequences supplied with
      robust taxonomies, is highly needed. To address this issue, we created ITSoneDB
      (available at http://itsonedb.cloud.ba.infn.it/) which in its current version
      hosts 985 240 ITS1 sequences spanning over 134 000 eukaryotic species. Each ITS1
      is mapped on the NCBI reference taxonomy with its start and end positions
      precisely annotated. ITSoneDB has been developed in agreement to the FAIR
      guidelines by enabling the users to query and download its content through a
      simple web-interface and access relevant metadata by cross-linking to European
      Nucleotide Archive.

PMID- 29036530
TI  - What does quality maternity care mean in a context of medical pluralism?
      Perspectives of women in Nigeria.
AB  - User priorities regarding quality care in contexts of medical pluralism are
      poorly documented. Drawing on group and individual interviews with women, we
      interrogate ideas of quality maternity care in the context of Nigeria's medical
      pluralism. We found complex utilization patterns for conventional, complementary
      and alternative maternity care services as well as ideas of quality maternity
      care that stress effective coordination and integration of different typologies
      of maternity health services; socially sensitive and truthful providers; and
      socioeconomic, physical and parochial forms of safety. Informal providers were
      the commonly reported source of maternal health services in the study. Maternal
      health services in the country were also generally viewed as poor quality,
      characterized by pervasive abuse, quackery and lack of commitment to the needs
      and sensitivities of women. Convenience, availability and affordability of
      maternal health services, as well as sociocultural factors were major influences
      on women's use of services. Results demonstrate the embeddedness of women's
      quality of care notions in the vast socioeconomic inequities that typify
      Nigeria's particular form of poorly regulated medical pluralism, raising need for
      strategies to strengthen the delivery, coordination and supervision of maternal
      health services in the country.

PMID- 29036531
TI  - SPATKIN: a simulator for rule-based modeling of biomolecular site dynamics on
      surfaces.
AB  - Summary: Rule-based modeling is a powerful approach for studying biomolecular
      site dynamics. Here, we present SPATKIN, a general-purpose simulator for rule
      based modeling in two spatial dimensions. The simulation algorithm is a lattice
      based method that tracks Brownian motion of individual molecules and the
      stochastic firing of rule-defined reaction events. Because rules are used as
      event generators, the algorithm is network-free, meaning that it does not require
      to generate the complete reaction network implied by rules prior to simulation.
      In a simulation, each molecule (or complex of molecules) is taken to occupy a
      single lattice site that cannot be shared with another molecule (or complex).
      SPATKIN is capable of simulating a wide array of membrane-associated processes,
      including adsorption, desorption and crowding. Models are specified using an
      extension of the BioNetGen language, which allows to account for spatial features
      of the simulated process. Availability and implementation: The C ++ source code
      for SPATKIN is distributed freely under the terms of the GNU GPLv3 license. The
      source code can be compiled for execution on popular platforms (Windows, Mac and
      Linux). An installer for 64-bit Windows and a macOS app are available. The source
      code and precompiled binaries are available at the SPATKIN Web site
      (http://pmbm.ippt.pan.pl/software/spatkin). Contact: spatkin.simulator@gmail.com.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29036533
TI  - gVolante for standardizing completeness assessment of genome and transcriptome
      assemblies.
AB  - Motivation: Along with the increasing accessibility to comprehensive sequence
      information, such as whole genomes and transcriptomes, the demand for assessing
      their quality has been multiplied. To this end, metrics based on sequence
      lengths, such as N50, have become a standard, but they only evaluate one aspect
      of assembly quality. Conversely, analyzing the coverage of pre-selected reference
      protein-coding genes provides essential content-based quality assessment, but the
      currently available pipelines for this purpose, CEGMA and BUSCO, do not have a
      user-friendly interface to serve as a uniform environment for assembly
      completeness assessment. Results: Here, we introduce a brand-new web server,
      gVolante, which provides an online tool for (i) on-demand completeness assessment
      of sequence sets by means of the previously developed pipelines CEGMA and BUSCO
      and (ii) browsing pre-computed completeness scores for publicly available data in
      its database section. Completeness assessments performed on gVolante report
      scores based on not just the coverage of reference genes but also on sequence
      lengths (e.g. N50 scaffold length), allowing quality control in multiple aspects.
      Using gVolante, one can compare the quality of original assemblies between their
      multiple versions (obtained through program choice and parameter tweaking, for
      example) and evaluate them in comparison to the scores of public resources found
      in the database section. Availability and implementation: gVoalte is freely
      available at https://gvolante.riken.jp/. Contact: shigehiro.kuraku@riken.jp.

PMID- 29036532
TI  - Behavioral pattern separation and its link to the neural mechanisms of fear
      generalization.
AB  - Fear generalization is a prominent feature of anxiety disorders and post
      traumatic stress disorder (PTSD). It is defined as enhanced fear responding to a
      stimulus that bears similarities, but is not identical to a threatening stimulus.
      Pattern separation, a hippocampal-dependent process, is critical for stimulus
      discrimination; it transforms similar experiences or events into non-overlapping
      representations. This study is the first in humans to investigate the extent to
      which fear generalization relies on behavioral pattern separation abilities.
      Participants (N = 46) completed a behavioral task taxing pattern separation, and
      a neuroimaging fear conditioning and generalization paradigm. Results show an
      association between lower behavioral pattern separation performance and increased
      generalization in shock expectancy scores, but not in fear ratings. Furthermore,
      lower behavioral pattern separation was associated with diminished recruitment of
      the subcallosal cortex during presentation of generalization stimuli. This region
      showed functional connectivity with the orbitofrontal cortex and ventromedial
      prefrontal cortex. Together, the data provide novel experimental evidence that
      pattern separation is related to generalization of threat expectancies, and
      reduced fear inhibition processes in frontal regions. Deficient pattern
      separation may be critical in overgeneralization and therefore may contribute to
      the pathophysiology of anxiety disorders and PTSD.

PMID- 29036534
TI  - Constitutive phenolic biomarkers identify naive Quercus agrifolia resistant to
      Phytophthora ramorum, the causal agent of sudden oak death.
AB  - Sudden oak death, caused by the invasive pathogen Phytophthora ramorum Werres, de
      Cock & Man in't Veld, can be deadly for Quercus agrifolia Nee (coast live oak,
      CLO). However, resistant trees have been observed in natural populations. The
      objective of this study was to examine if pre-attack (constitutive) levels of
      phenolic compounds can be used as biomarkers to identify trees likely to be
      resistant. Naive trees were selected from a natural population and phloem was
      sampled for analysis of constitutive phenolics. Following P. ramorum inoculation,
      trees were phenotyped to determine disease susceptibility and constitutive
      phenolic biomarkers of resistance were identified. Seasonal variation in phloem
      phenolics was also assessed in a subset of non-inoculated trees. Four biomarkers,
      including myricitrin and three incompletely characterized flavonoids, together
      correctly classified 80% of trees. Biomarker levels were then used to predict
      survival of inoculated CLO and the proportion of resistant trees within a subset
      of non-inoculated trees from the same population. Levels of five phenolics were
      significantly affected by season, but with no pronounced variation in average
      levels among seasons. These results suggest that pre-infection levels of specific
      phenolic compounds (i.e., biomarkers) can identify trees naturally resistant to
      this invasive forest pathogen. Knowledge of resistant trees within natural
      populations may be useful for conserving and breeding resistant trees and for
      disease management.

PMID- 29036535
TI  - pLoc-mAnimal: predict subcellular localization of animal proteins with both
      single and multiple sites.
AB  - Motivation: Cells are deemed the basic unit of life. However, many important
      functions of cells as well as their growth and reproduction are performed via the
      protein molecules located at their different organelles or locations. Facing
      explosive growth of protein sequences, we are challenged to develop fast and
      effective method to annotate their subcellular localization. However, this is by
      no means an easy task. Particularly, mounting evidences have indicated proteins
      have multi-label feature meaning that they may simultaneously exist at, or move
      between, two or more different subcellular location sites. Unfortunately, most of
      the existing computational methods can only be used to deal with the single-label
      proteins. Although the 'iLoc-Animal' predictor developed recently is quite
      powerful that can be used to deal with the animal proteins with multiple
      locations as well, its prediction quality needs to be improved, particularly in
      enhancing the absolute true rate and reducing the absolute false rate. Results:
      Here we propose a new predictor called 'pLoc-mAnimal', which is superior to iLoc
      Animal as shown by the compelling facts. When tested by the most rigorous cross
      validation on the same high-quality benchmark dataset, the absolute true success
      rate achieved by the new predictor is 37% higher and the absolute false rate is
      four times lower in comparison with the state-of-the-art predictor. Availability
      and implementation: To maximize the convenience of most experimental scientists,
      a user-friendly web-server for the new predictor has been established at
      http://www.jci-bioinfo.cn/pLoc-mAnimal/, by which users can easily get their
      desired results without the need to go through the complicated mathematics
      involved. Contact: xxiao@gordonlifescience.org or kcchou@gordonlifescience.org.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29036536
TI  - wft4galaxy: a workflow testing tool for galaxy.
AB  - Motivation: Workflow managers for scientific analysis provide a high-level
      programming platform facilitating standardization, automation, collaboration and
      access to sophisticated computing resources. The Galaxy workflow manager provides
      a prime example of this type of platform. As compositions of simpler tools,
      workflows effectively comprise specialized computer programs implementing often
      very complex analysis procedures. To date, no simple way to automatically test
      Galaxy workflows and ensure their correctness has appeared in the literature.
      Results: With wft4galaxy we offer a tool to bring automated testing to Galaxy
      workflows, making it feasible to bring continuous integration to their
      development and ensuring that defects are detected promptly. wft4galaxy can be
      easily installed as a regular Python program or launched directly as a Docker
      container-the latter reducing installation effort to a minimum. Availability and
      implementation: Available at https://github.com/phnmnl/wft4galaxy under the
      Academic Free License v3.0. Contact: marcoenrico.piras@crs4.it.

PMID- 29036538
TI  - sTLR4/MD-2 complex inhibits colorectal cancer migration and invasiveness in vitro
      and in vivo by lncRNA H19 down-regulation.
AB  - Long non-coding RNAs (lncRNAs) have multiple functions in gene regulation and
      during cellular processes. However, the functional roles of lncRNAs in colorectal
      cancer (CRC) have not yet been well understood. In our previous study, we
      demonstrated that sTLR4/MD-2 complex can inhibit CRC in vitro and in vivo by
      targeting LPS. Therefore, the aim of the present study is to investigate the
      expression of lncRNA H19 in CRC and to evaluate its effect on the inhibition of
      sTLR4/MD-2 complex. The expression of H19 is measured in 63 CRC tumor tissues and
      adjacent normal tissues by quantitative real-time PCR (qRT-PCR). The effects of
      H19 on migration and invasiveness are evaluated by wound healing assay, migration
      and invasion assays. Results showed that H19 is significantly overexpressed in
      cancerous tissues and CRC cell lines compared with adjacent normal tissues and a
      normal human intestinal epithelial cell line. Moreover, H19 overexpression is
      closely associated with CRC patients. Our in vitro data indicated that knockdown
      of H19 inhibits the migration and invasiveness of CRC cells. And in vivo sTLR4/MD
      2 complex inhibits tumor growth in mice and the expression of H19 is down
      regulated. These results suggest that sTLR4/MD-2 complex inhibits CRC migration
      and invasiveness in vitro and in vivo by lncRNA H19 down-regulation.

PMID- 29036537
TI  - 2'-Fluoroarabinonucleic acid modification traps G-quadruplex and i-motif
      structures in human telomeric DNA.
AB  - Human telomeres and promoter regions of genes fulfill a significant role in
      cellular aging and cancer. These regions comprise of guanine and cytosine-rich
      repeats, which under certain conditions can fold into G-quadruplex (G4) and i
      motif structures, respectively. Herein, we use UV, circular dichroism and NMR
      spectroscopy to study several human telomeric sequences and demonstrate that G4/i
      motif-duplex interconversion kinetics are slowed down dramatically by 2'-beta
      fluorination and the presence of G4/i-motif-duplex junctions. NMR-monitored
      kinetic experiments on 1:1 mixtures of native and modified C- and G-rich human
      telomeric sequences reveal that strand hybridization kinetics are controlled by
      G4 or i-motif unfolding. Furthermore, we provide NMR evidence for the formation
      of a hybrid complex containing G4 and i-motif structures proximal to a duplex DNA
      segment at neutral pH. While the presence of i-motif and G4 folds may be mutually
      exclusive in promoter genome sequences, our results suggest that they may co
      exist transiently as intermediates in telomeric sequences.

PMID- 29036539
TI  - Immune cells and autoantibodies in pulmonary arterial hypertension.
AB  - Analyses of immunity in pulmonary arterial hypertension (PAH) support the notion
      that maladaptation of the immune response exists. Altered immunity is an
      increasingly recognized feature of PAH. Indeed, a delicate balance between
      immunity and tolerance exists and any disturbance may result in chronic
      inflammation or autoimmunity. This is suggested by infiltration of various immune
      cells (e.g. macrophages, T and B lymphocytes) in remodeled pulmonary vessels. In
      addition, several types of autoantibodies directed against antinuclear antigens,
      endothelial cells (ECs) and fibroblasts have been found in idiopathic and
      systemic sclerosis-associated PAH. These autoantibodies may play an important
      role in EC apoptosis and in the expression of cell adhesion molecules. This
      review article provides an overview of immunity pathways highlighting their
      potential roles in pulmonary vascular remodeling in PAH and the possibility of
      future targeted therapy.

PMID- 29036540
TI  - Tackling anti-microbial resistance: ethical framework for rational antibiotic
      use.
AB  - Background: To reduce the effect of antimicrobial resistance and to preserve
      antibiotic effectiveness, clinical guidelines and health policy documents call
      for the rational use of antibiotics, which aims to reduce unnecessary or
      minimally effective antibiotic use. Methods: Through ethical analysis, we show
      that rational use programmes can lead to ethical conflicts, because they
      sometimes place patients at risk of harm-for example, a delayed switch to second
      line antibiotics for community-acquired pneumonia can lead to substantial
      increases in mortality. Results: Implementing the rational use of antibiotics can
      lead to conflicts between promoting patients' clinical interests and preserving
      antibiotic effectiveness for future use. The resulting ethical dilemma for
      clinicians, patients and policy makers has so far not been adequately addressed.
      Conclusions: Existing guidance for acceptable risks in clinical research can help
      to define risk thresholds for the rational use of antibiotics. We develop an
      ethical framework that allows clinicians and policy-makers to evaluate policies
      for rational antibiotic use in six practical steps. This framework can help guide
      clinical practice and health policy.

PMID- 29036541
TI  - Simple fixed-effects inference for complex functional models.
AB  - We propose simple inferential approaches for the fixed effects in complex
      functional mixed effects models. We estimate the fixed effects under the
      independence of functional residuals assumption and then bootstrap independent
      units (e.g. subjects) to conduct inference on the fixed effects parameters.
      Simulations show excellent coverage probability of the confidence intervals and
      size of tests for the fixed effects model parameters. Methods are motivated by
      and applied to the Baltimore Longitudinal Study of Aging, though they are
      applicable to other studies that collect correlated functional data.

PMID- 29036543
TI  - Pilot-Reported Beta-Blockers Identified by Forensic Toxicology Analysis of
      Postmortem Specimens.
AB  - Introduction: This study compared beta-blockers reported by pilots with the
      medications found by postmortem toxicology analysis of specimens received from
      fatal aviation accidents between 1999 and 2015. Several studies have compared
      drugs using the standard approach: Compare the drug found by toxicology analysis
      with the drug reported by the pilot. This study uniquely examined first the pilot
      reported medication and then compared it to that detected by toxicology analysis.
      This study will serve two purposes: (i) to determine the capability of a
      toxicology laboratory to detect reported medications, and (ii) to identify pilots
      with medications below detectable limits. Method: All information required for
      this study was extracted from the Toxicology Data Base system and was searched
      using ToxFlo or SQL Server Management Studio. The following information was
      collected and analyzed: pilot-reported trade and/or generic drug, date specimens
      received, time of accident, type of aviation operations (CFR), state, pilot
      level, age, class of medical, specimen type, specimen concentration, dose
      reported, frequency reported associated with the accident, quantity reported,
      National Transportation Safety Board (NTSB) accident event number, and all NTSB
      reports. Results: There were 319 pilots that either reported taking a beta
      blocker or were found to be taking a beta-blocker by postmortem toxicology
      analysis. Discussion: Time of death, therapeutic concentration and specimen type
      were found to be factors in the ability of the laboratory to detect beta
      blockers. Beta-blockers taken by pilots will, in most cases, be found by a
      competent postmortem forensic toxicology laboratory at therapeutic
      concentrations. The dose taken by the pilot was not found to be a factor in the
      ability of the laboratory to identify beta-blockers. Time of dose, route of
      administration, specimen tested and therapeutic concentration of the drug were
      found to be factors in the ability of the laboratory to identify beta-blockers in
      postmortem specimens.

PMID- 29036544
TI  - Response to the letter from Warren et al.

PMID- 29036542
TI  - Database Resources of the BIG Data Center in 2018.
AB  - The BIG Data Center at Beijing Institute of Genomics (BIG) of the Chinese Academy
      of Sciences provides freely open access to a suite of database resources in
      support of worldwide research activities in both academia and industry. With the
      vast amounts of omics data generated at ever-greater scales and rates, the BIG
      Data Center is continually expanding, updating and enriching its core database
      resources through big-data integration and value-added curation, including
      BioCode (a repository archiving bioinformatics tool codes), BioProject (a
      biological project library), BioSample (a biological sample library), Genome
      Sequence Archive (GSA, a data repository for archiving raw sequence reads),
      Genome Warehouse (GWH, a centralized resource housing genome-scale data), Genome
      Variation Map (GVM, a public repository of genome variations), Gene Expression
      Nebulas (GEN, a database of gene expression profiles based on RNA-Seq data),
      Methylation Bank (MethBank, an integrated databank of DNA methylomes), and
      Science Wikis (a series of biological knowledge wikis for community annotations).
      In addition, three featured web services are provided, viz., BIG Search (search
      as a service; a scalable inter-domain text search engine), BIG SSO (single sign
      on as a service; a user access control system to gain access to multiple
      independent systems with a single ID and password) and Gsub (submission as a
      service; a unified submission service for all relevant resources). All of these
      resources are publicly accessible through the home page of the BIG Data Center at
      http://bigd.big.ac.cn.

PMID- 29036545
TI  - Rhizarthrosis in banknote processing workers: a retrospective cohort study.
AB  - Background: Rhizarthrosis, or osteoarthritis of the base of the thumb, is a
      common condition affecting 10-30% of the population over the age of 60. Whether
      it is an occupational disease has been the subject of debate as epidemiological
      studies on the correlation between physical stress and the presence of
      rhizarthrosis have shown conflicting results. Aims: To study the correlation
      between the prevalence of rhizarthrosis and the time spent by employees manually
      processing banknotes at the National Bank of Belgium (NBB). Methods: We followed
      NBB employees currently or previously holding job titles involving the manual or
      automated processing of banknotes. Each participant's job history was carefully
      reconstructed and the number of months holding certain job titles determined.
      Each participant was clinically and radiologically examined for the presence of
      rhizarthrosis in both hands. Its presence was scored by a combination of clinical
      and radiological criteria. Results: There were 195 participants. The prevalence
      of rhizarthrosis was 27% in women (mean age: 52.3 +/- 4.4 years) and 17% in men
      (mean age: 53.2). The odds ratio (OR) for rhizarthrosis after 10 years' full-time
      overall exposure was significantly higher [OR 10 years: 1.53 (1.03-2.28)].
      However, one particular job, 'manual counting', described by participants as
      highly straining and severely taxing on the thumbs, did not show a significantly
      higher prevalence of rhizarthrosis. Conclusions: Our study confirmed the
      correlation between the presence of rhizarthrosis and age, gender and general
      manual labour, in particular banknote processing, but found no link with one
      specific job-manual counting.

PMID- 29036546
TI  - CrocoBLAST: Running BLAST efficiently in the age of next-generation sequencing.
AB  - Summary: CrocoBLAST is a tool for dramatically speeding up BLAST+ execution on
      any computer. Alignments that would take days or weeks with NCBI BLAST+ can be
      run overnight with CrocoBLAST. Additionally, CrocoBLAST provides features
      critical for NGS data analysis, including: results identical to those of BLAST+;
      compatibility with any BLAST+ version; real-time information regarding
      calculation progress and remaining run time; access to partial alignment results;
      queueing, pausing, and resuming BLAST+ calculations without information loss.
      Availability and implementation: CrocoBLAST is freely available online, with
      ample documentation (webchem.ncbr.muni.cz/Platform/App/CrocoBLAST). No
      installation or user registration is required. CrocoBLAST is implemented in C,
      while the graphical user interface is implemented in Java. CrocoBLAST is
      supported under Linux and Windows, and can be run under Mac OS X in a Linux
      virtual machine. Contact: jkoca@ceitec.cz. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29036547
TI  - B-Type Natriuretic Peptide and Ventricular Dysfunction in the Prediction of
      Cardiovascular Events and Death in Hypertension.
AB  - BACKGROUND: The prevalence and morbidity of hypertension continues to grow
      globally and improved methods of stratifying risk and identifying organ damage
      earlier are required. Methods such as echocardiography and population-based risk
      scores are suggested by guidelines as approaches to aid in risk stratification.
      However, biomarkers such as natriuretic peptides may help provide such an
      approach. METHODS: We analyzed data from the screening to prevent heart failure
      cohort including participants with hypertension with and without a history of a
      cardiovascular (CV) event at baseline. We investigated the ability of ventricular
      dysfunction on echocardiography at baseline and of B-type natriuretic peptide
      (BNP) levels in predicting future major adverse CV events (MACE) and death. We
      also investigated the use of Systematic COronary Risk Evaluation (SCORE) to
      predict these events in the uncomplicated cohort. RESULTS: In total, 572 patients
      (427 with uncomplicated hypertension) were included. Thirty-three patients had
      MACE or died during follow up. In a univariate analysis, BNP was predictive of
      MACE and death in all groups. Ventricular dysfunction was not predictive of MACE
      and death in any group. Both BNP and SCORE had predictive value in this category.
      However, the magnitude and strength of the continuous association between BNP and
      events is higher and BNP adds significantly to the predictive value of SCORE as
      determined by likelihood ratios. The net reclassification improvement for BNP
      compared to stage B heart failure was 0.20. CONCLUSION: This study demonstrates
      that in patients with hypertension, BNP is superior to ventricular dysfunction on
      echocardiography in the prediction of risk of MACE and death in a community-based
      cohort of patients with complicated and uncomplicated hypertension.

PMID- 29036548
TI  - Acute Response to a 2-Minute Isometric Exercise Test Predicts the Blood Pressure
      Lowering Efficacy of Isometric Resistance Training in Young Adults.
AB  - BACKGROUND: This work aimed to explore whether different forms of a simple
      isometric exercise test could be used to predict the blood pressure (BP)-lowering
      efficacy of different types of isometric resistance training (IRT) in healthy
      young adults. In light of the emphasis on primary prevention of hypertension,
      identifying those with normal BP who will respond to IRT is important. Also,
      heightened BP reactivity increases hypertension risk, and as IRT reduces BP
      reactivity in patients with hypertension, it warrants further investigation in a
      healthy population. METHODS: Forty-six young men and women (24 +/- 5 years; 116
      +/- 10/ 68 +/- 8 mm Hg) were recruited from 2 study sites: Windsor, Canada (n =
      26; 13 women), and Northampton, United Kingdom (n = 20; 10 women). Resting BP and
      BP reactivity to an isometric exercise test were assessed prior to and following
      10 weeks of thrice weekly IRT. Canadian participants trained on a handgrip
      dynamometer (isometric handgrip, IHG), while participants in the UK trained on an
      isometric leg extension dynamometer (ILE). RESULTS: Men and women enrolled in
      both interventions demonstrated significant reductions in systolic BP (P < 0.001)
      and pulse pressure (P < 0.05). Additionally, test-induced systolic BP changes to
      IHG and ILE tests were associated with IHG and ILE training-induced reductions in
      systolic BP after 10 weeks of training, respectively (r = 0.58 and r = 0.77; for
      IHG and ILE; P < 0.05). CONCLUSIONS: The acute BP response to an isometric
      exercise test appears to be a viable tool to identify individuals who may respond
      to traditional IRT prescription.

PMID- 29036549
TI  - Physiological and pathological gestational cardiac hypertrophy: what can we learn
      from rodents?

PMID- 29036550
TI  - Perceived Interpersonal Discrimination and Older Women's Mental Health:
      Accumulation Across Domains, Attributions, and Time.
AB  - Experiencing discrimination is associated with poor mental health, but how
      cumulative experiences of perceived interpersonal discrimination across
      attributes, domains, and time are associated with mental disorders is still
      unknown. Using data from the Study of Women's Health Across the Nation (1996
      2008), we applied latent class analysis and generalized linear models to estimate
      the association between cumulative exposure to perceived interpersonal
      discrimination and older women's mental health. We found 4 classes of perceived
      interpersonal discrimination, ranging from cumulative exposure to discrimination
      over attributes, domains, and time to none or minimal reports of discrimination.
      Women who experienced cumulative perceived interpersonal discrimination over time
      and across attributes and domains had the highest risk of depression (Center for
      Epidemiologic Studies Depression Scale score >=16) compared with women in all
      other classes. This was true for all women regardless of race/ethnicity, although
      the type and severity of perceived discrimination differed across racial/ethnic
      groups. Cumulative exposure to perceived interpersonal discrimination across
      attributes, domains, and time has an incremental negative long-term association
      with mental health. Studies that examine exposure to perceived discrimination due
      to a single attribute in 1 domain or at 1 point in time underestimate the
      magnitude and complexity of discrimination and its association with health.

PMID- 29036551
TI  - Comparative study of the growth and nutritional status of Brazilian and Nigerian
      school-aged children with sickle cell disease.
AB  - Background: Comparative studies of patients in different
      sociogeographic/ecological zones may unravel potential environmental and
      nutritional factors influencing disease phenotype. In sickle cell disease (SCD),
      differential access to comprehensive care may influence their growth and
      nutritional status. Methods: From June 2015 to February 2016, steady-state
      nutritional parameters of 109 Brazilian and 95 Nigerian children with SCD
      attending routine clinic visits at Universidade Federal de Sao Paulo, Brazil and
      Obafemi Awolowo University Teaching Hospital, Ile-Ife (Ilesa unit), respectively,
      were compared. Results: A relatively high proportion of the children in both
      centres (23.5%) were wasted [body-mass index (BMI)-for-age z-score<-2). BMI-for
      age z-score, height-for-age z-score, upper arm fat area and fat percentage were
      lower in the Nigerian cohorts. More Nigerians, 29.5% (28/95) against 18.3%
      (20/109) were wasted, and had short stature, [12.6% (12/95) vs. 3.7% (4/109)]
      than Brazilians. A higher proportion of Brazilian patients were overweight or
      obese (9.2 vs. 4.3%), and taller for age (15.6 vs. 8.4%). None of the Nigerian
      patients had severe vitamin D deficiency, only 12.6% (12/95) had suboptimal
      vitamin D and 1.1% (1/95) had low serum zinc levels, unlike 79.8% (87/109) of the
      Brazilian patients with suboptimal vitamin D and 10.1% (11/109) with low zinc.
      Conclusion: Undernutrition is still prevalent among the two cohorts. Nigerian
      patients were thinner and had reduced linear growth for age. This observation
      justifies the continued need for specialized nutritional care for children with
      SCD. In addition to hydroxyurea therapy, research is needed to determine
      appropriate nutritional intervention and exercise regimens for these children.

PMID- 29036552
TI  - Using foliar spectral properties to assess the effects of drought on plant water
      potential.
AB  - Drought frequency is predicted to increase in future environments. Leaf water
      potential (PsiLW) is commonly used to evaluate plant water status, but
      traditional measurements can be logistically difficult and require destructive
      sampling. We used reflectance spectroscopy to characterize variation in PsiLW of
      Quercus oleoides Schltdl. & Cham. under differential water availability and
      tested the ability to predict pre-dawn PsiLW (PDPsiLW) using spectral data
      collected hours after pressure chamber measurements on dark-acclimated leaves.
      PsiLW was measured with a Scholander pressure chamber. Leaf reflectance was
      collected at one or both of two time points: immediately (PsiLW) and ~5 h after
      pressure chamber measurements (PDPsiLW). Predictive models were constructed using
      partial least-squares regression. Model performance was evaluated using
      coefficient of determination (R2), root-mean-square error (RMSE), bias, and the
      percent RMSE of the data range (%RMSE). PsiLW and PDPsiLW were well predicted
      using spectroscopic models and successfully estimated a wide variation in PsiLW
      (light- or dark-acclimated leaves) as well as PDPsiLW (dark-acclimated leaves
      only). Mean PsiLWR2, RMSE and bias values were 0.65, 0.51 MPa and 0.09,
      respectively, with a %RMSE between 8% and 20%, while mean PDPsiLWR2, RMSE and
      bias values were 0.60, 0.44 MPa and 0.01, respectively, with a %RMSE between 9%
      and 20%. Estimates of PDPsiLW produced similar statistical outcomes when
      analyzing treatment effects on PDPsiLW as those found using reference pressure
      chamber measurements. These findings highlight a promising approach to evaluate
      plant responses to environmental change by providing rapid measurements that can
      be used to estimate plant water status as well as demonstrating that
      spectroscopic measurements can be used as a surrogate for standard, reference
      measurements in a statistical framework.

PMID- 29036553
TI  - Two-Track Control of Cellular Machinery for Photomovement in Spirogyra varians
      (Streptophyta, Zygnematales).
AB  - Plants and freshwater algae devoid of flagella evolved various photomovements to
      optimize their photosynthetic efficiency. The filaments of Spirogyra varians
      exhibit complex swaying and undulating movement and form a compact mat which
      enables them to adjust their light exposure. Photomovement of filament fragments
      (1-10 cells) was analyzed using various photoreceptor and cytoskeleton inhibitors
      under monochromatic light. Different patterns of movement were observed under red
      and blue light. The filaments showed positive phototropism under blue light.
      Under red light, the filaments bent to undulating shape, but rapidly became
      unbent by a short exposure to far-red light suggesting the involvement of
      phytochrome in this movement. The mechanical effector for the red-light response
      was microtubules; the movement was inhibited effectively by the microtubule
      inhibitor, oryzalin. The blue-light movement was partially inhibited by the
      single treatment of either cytochalasin D or oryzalin, but was completely blocked
      when both chemicals were applied together. Phototropin-signaling inhibitors,
      wortmannin and LY294002, reversibly inhibited the blue-light movement. Caffeine
      treatment reversibly stopped the blue-light movement, while the red-light
      movement was not affected by calcium inhibitors. Our results suggest that the
      complex photomovement of S. varians is the result of a two-track control of
      microtubules and microfilaments signaled by the combination of phytochrome and
      phototropin-like receptors.

PMID- 29036554
TI  - Contrast venography vs. microwire assisted axillary venipuncture for
      cardiovascular implantable electronic device implantation.
AB  - Aims: This study was conducted to compare the safety and efficacy of microwire
      assisted technique with contrast venography guided axillary venipuncture in
      patients undergoing cardiovascular implantable electronic device (CIED)
      implantation. Methods and results: This prospective randomized study included 212
      consecutive adult patients undergoing CIED implantation at our institute between
      2013 and 2015. Patients were randomized to either venography guided technique
      (Group I; n = 105) or microwire assisted technique (Group II; n = 107) for
      axillary venipuncture. In Group I axillary venogram was used as a roadmap for
      guiding the puncture. In Group II, a 0.014 inch hydrophilic coronary guidewire
      ('microwire') was introduced through the ipsilateral antecubital vein and
      puncture needle was aimed to hit the microwire over the first or second rib.
      Outcome measures including technical success rates; number of attempts to
      successful puncture; puncture duration; fluoroscopy times and adverse events were
      compared in the two groups. Overall success rates were similar in both groups
      (97.4% in Group I and 100% in Group II, P = 0.061). We demonstrated significantly
      higher first attempt success rates; shorter puncture durations and fluoroscopy
      times; and lower number of attempts to successful puncture with microwire
      assisted technique (89.3% vs. 65.6%; 36.7 +/- 23.1 s vs. 67.8 +/- 44.9 s; 62.4 +/
      35.3 s vs. 118.9 +/- 63.2 s; and 1.21 +/- 0.82 vs. 2.16 +/- 1.54 respectively, P
      < 0.001). Adverse event rates were significantly lower with microwire assisted
      technique (0.9% vs. 8.6%, P = 0.009). Conclusion: Microwire assisted technique is
      a simple, quicker, safer and more efficacious alternative to contrast venography
      guided axillary venipuncture.

PMID- 29036555
TI  - Cultural capital factors associated with life satisfaction in Korean baby
      boomers.
AB  - Background: As aging baby boomers retire, cultural capital is expected to play a
      major role in representing new types of need for social inclusion for this group
      of people. This study aims to examine the association between cultural capital
      and life satisfaction among Korean baby boomers born between 1955 and 1963.
      Methods: Data on 297 baby boomers were extracted from the 2007 Korean General
      Social Survey and multiple regression models were tested. Results: The findings
      indicated that acquired cultural capital (i.e. experiences of private art and
      culture education and diverse participation in art and cultural activities) had a
      significant association with a higher level of life satisfaction, whereas
      inherited cultural capital (i.e. paternal educational level) was not related to
      life satisfaction among Korean baby boomers. Conclusions: The findings point to
      the potential benefits of acquired cultural capital as a means to promote the
      life satisfaction of the baby boom generation.

PMID- 29036557
TI  - Standardizing biomass reactions and ensuring complete mass balance in genome
      scale metabolic models.
AB  - Motivation: In a genome-scale metabolic model, the biomass produced is defined to
      have a molecular weight (MW) of 1 g mmol-1. This is critical for correctly
      predicting growth yields, contrasting multiple models and more importantly
      modeling microbial communities. However, the standard is rarely verified in the
      current practice and the chemical formulae of biomass components such as
      proteins, nucleic acids and lipids are often represented by undefined side groups
      (e.g. X, R). Results: We introduced a systematic procedure for checking the
      biomass weight and ensuring complete mass balance of a model. We identified
      significant departures after examining 64 published models. The biomass weights
      of 34 models differed by 5-50%, while 8 models have discrepancies >50%. In total
      20 models were manually curated. By maximizing the original versus corrected
      biomass reactions, flux balance analysis revealed >10% differences in growth
      yields for 12 of the curated models. Biomass MW discrepancies are accentuated in
      microbial community simulations as they can cause significant and systematic
      errors in the community composition. Microbes with underestimated biomass MWs are
      overpredicted in the community whereas microbes with overestimated biomass
      weights are underpredicted. The observed departures in community composition are
      disproportionately larger than the discrepancies in the biomass weight estimate.
      We propose the presented procedure as a standard practice for metabolic
      reconstructions. Availability and implementation: The MALTAB and Python scripts
      are available in the Supplementary Material. Contact: costas@psu.edu or
      joshua.chan@connect.polyu.hk. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29036556
TI  - Deficit in PINK1/PARKIN-mediated mitochondrial autophagy at late stages of
      dystrophic cardiomyopathy.
AB  - Aims: Duchenne muscular dystrophy (DMD) is an inherited devastating muscle
      disease with severe and often lethal cardiac complications. Emerging evidence
      suggests that the evolution of the pathology in DMD is accompanied by the
      accumulation of mitochondria with defective structure and function. Here, we
      investigate whether defects in the housekeeping autophagic pathway contribute to
      mitochondrial and metabolic dysfunctions in dystrophic cardiomyopathy. Methods
      and results: We employed various biochemical and imaging techniques to assess
      mitochondrial structure and function as well as to evaluate autophagy, and
      specific mitochondrial autophagy (mitophagy), in hearts of mdx mice, an animal
      model of DMD. Our results indicate substantial structural damage of mitochondria
      and a significant decrease in ATP production in hearts of mdx animals, which
      developed cardiomyopathy. In these hearts, we also detected enhanced autophagy
      but paradoxically, mitophagy appeared to be suppressed. In addition, we found
      decreased levels of several proteins involved in the PINK1/PARKIN mitophagy
      pathway as well as an insignificant amount of PARKIN protein phosphorylation at
      the S65 residue upon induction of mitophagy. Conclusions: Our results suggest
      faulty mitophagy in dystrophic hearts due to defects in the PINK1/PARKIN pathway.

PMID- 29036558
TI  - MethRaFo: MeDIP-seq methylation estimate using a Random Forest Regressor.
AB  - Motivation: Profiling of genome wide DNA methylation is now routinely performed
      when studying development, cancer and several other biological processes.
      Although Whole genome Bisulfite Sequencing provides high-quality methylation
      measurements at the resolution of nucleotides, it is relatively costly and so
      several studies have used alternative methods for such profiling. One of the most
      widely used low cost alternatives is MeDIP-Seq. However, MeDIP-Seq is biased for
      CpG enriched regions and thus its results need to be corrected in order to
      determine accurate methylation levels. Results: Here we present a method for
      correcting MeDIP-Seq results based on Random Forest regression. Applying the
      method to real data from several different tissues (brain, cortex, penis) we show
      that it achieves almost 4 fold decrease in run time while increasing accuracy by
      as much as 20% over prior methods developed for this task. Availability and
      implementation: MethRaFo is freely available as a python package (with a R
      wrapper) at https://github.com/phoenixding/methrafo. Contact: zivbj@cs.cmu.edu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29036559
TI  - The brisk-standing-test for long QT syndrome in prepubertal school children:
      defining normal.
AB  - Aims: Long QT syndrome (LQTS) is associated with malignant arrhythmias and sudden
      death from birth to advanced age. Prolongation of the QT-interval, may however be
      concealed on standard electrocardiograms (ECG). The brisk-standing-test (BST) was
      developed to guide LQTS-diagnosis and treatment in adults. We hypothesized that
      the BST may be used in prepubertal children to identify LQTS subjects.
      Accordingly, reference values for the BST should be available to prevent
      incorrect diagnosis and treatment of LQTS. In this study, we aim to present
      reference values for prepubertal children. Methods and results: Healthy,
      prepubertal children, aged 7-13 years underwent a standard supine resting ECG and
      during continuous ECG recording performed a BST. The QT-interval and heart rate
      corrected QTc were measured during the different BST stages. Fifty-seven
      children, 29 boys (10.2 +/- 1.1 years) and 28 girls (9.9 +/- 1.1 years) were
      included. Baseline characteristics and response to standing were not
      statistically different for boys and girls: mean supine pre-standing heart rate
      74 +/- 9 vs. 77 +/- 9 bpm, supine pre-standing QTc 406 +/- 27 vs. 407 +/- 17 ms,
      maximal heart rate upon standing 109 +/- 11 vs. 112 +/- 11 bpm, and QTc at
      maximal heart rate 484 +/- 29 vs. 487 +/- 35 ms. The QT interval corrected for
      heart rate-prolongation at maximal tachycardia after standing was 79 +/- 26 (19
      144) ms, which is significantly longer than previously published values in adults
      (50+/- 30 ms). Conclusions: The QT interval corrected for heart rate prolongation
      after brisk standing in healthy prepubertal children is more pronounced than in
      healthy adults. This finding advocates distinct prepubertal cut-off values
      because using adult values for prepubertal children would yield false positive
      results with the risk of incorrect LQTS-diagnosis and overtreatment.

PMID- 29036560
TI  - Wound haematoma following defibrillator implantation: incidence and predictors in
      the Shockless Implant Evaluation (SIMPLE) trial: comment.

PMID- 29036561
TI  - Acrokeratosis paraneoplastica (Bazex syndrome).

PMID- 29036562
TI  - nandb-number and brightness in R with a novel automatic detrending algorithm.
AB  - Summary: An R package for performing number and brightness image analysis, with
      the implementation of a novel automatic detrending algorithm. Availability and
      implementation: Available at https://github.com/rorynolan/nandb for all
      platforms. Contact: rnolan@well.ox.ac.uk or spadilla@well.ox.ac.uk. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29036563
TI  - Loss of CD15 expression in clear cell renal cell carcinoma is correlated with
      worse prognosis in Chinese patients.
AB  - Purpose: To explore the role of CD15 expression in the prognosis of clear cell
      renal cell carcinoma (ccRCC) in Chinese patients. Methods: The study included 301
      patients who had undergone surgery for localized ccRCC. All paraffin-embedded
      tumor sections were collected to make a set of tissue microarrays. CD15
      expression was assessed by immunohistochemistry. The relationship between CD15
      expression and survival parameters, clinicopathology features was assessed.
      Kaplan-Meier and Cox proportional hazards model were utilized to determine the
      correlation between CD15 expression and overall survival (OS). Results: The
      median follow-up time was 54.6 months (range, 3-121 months). The positive rate of
      CD15 expression was 81.7% (246/301). The cut-off value of CD15 expression was
      defined as the maximum for Youden index by plotting the receiver operating
      characteristic curve for survival status. As the threshold was 0.5, all cases
      were divided into two groups: positive expression group and negative expression
      group. In correlation analysis, loss of CD15 expression was correlated with
      female gender, higher Fuhrman nuclear grade, with sarcomatoid differentiation,
      with necrosis, and with vascular invasion. Kaplan-Meier analysis indicated that
      the OS time of patients with loss of CD15 expression was shorter than that of
      patients with positive CD15 expression (P = 0.013). Conclusion: CD15 is a
      significant prognostic factor in clear cell renal cell carcinoma.

PMID- 29036564
TI  - Elabela-APJ axis: a novel therapy target for cardiovascular diseases.

PMID- 29036565
TI  - Long-Term Risk of Acute Myocardial Infarction, Stroke, and Death With Outpatient
      Use of Clarithromycin: A Retrospective Cohort Study.
AB  - In a retrospective cohort study of patients enrolled in the UK Clinical Practice
      Research Datalink during 2000-2013, we evaluated long-term risks of death,
      stroke, and acute myocardial infarction (AMI) in adults prescribed
      clarithromycin. Patients were outpatients aged 40-85 years, who were prescribed
      clarithromycin (n = 287,748), doxycycline (n = 267,729), or erythromycin (n =
      442,999), or Helicobacter pylori eradication therapy with a proton pump
      inhibitor, amoxicillin, and either clarithromycin (n = 27,639) or metronidazole
      (n = 14,863). We analyzed time to death, stroke, or AMI with Cox proportional
      hazards regression. The long-term hazard ratio for death following 1
      clarithromycin versus 1 doxycycline prescription was 1.29 (95% confidence
      interval (CI): 1.21, 1.25), increasing to 1.62 (95% CI: 1.43, 1.84) for >=5
      prescriptions of clarithromycin versus >=5 prescriptions for doxycycline.
      Erythromycin showed smaller risks in comparison with doxycycline. Stroke and AMI
      incidences were also increased after clarithromycin but with smaller hazard
      ratios than for mortality. For H. pylori eradication, the hazard ratio for
      mortality following clarithromycin versus metronidazole regimens was 1.09 (95%
      CI: 1.00, 1.18) overall, and it was higher (hazard ratio = 1.65, 95% CI: 0.88,
      3.08) following >=2 prescriptions in subjects not on statins at baseline.
      Outpatient clarithromycin use was associated with long-term mortality increases,
      with evidence for a similar, smaller increase with erythromycin.

PMID- 29036567
TI  - Extra-pituitary expressed follicle-stimulating hormone: Is it physiologically
      important?
AB  - Pituitary gonadotropes synthesize and secrete follicle-stimulating hormone (FSH).
      FSH is a heterodimer that consists of an alpha- and beta-subunit. The alpha
      subunit is common to other pituitary and placental glycoprotein hormones, and the
      beta-subunit is the hormone/receptor-specific subunit. Although the pituitary is
      the main tissue that accounts for circulating hormone, previous and recent
      reports indicate extra-pituitary sources of FSH production including mouse
      gonads, human stomach, prostate, umbilical cord vein endothelial cells, uterine
      myometrium, placenta, and chicken abdominal adipose tissue. Whether extra
      pituitary derived FSH exerts any physiologically significant actions is not
      known. In this review, we have comprehensively analyzed the expression of mRNAs
      that encode mouse and human FSH subunits and also their corresponding expressed
      sequence tags in normal tissues, cancer cell lines, and primary tumors by public
      database mining. We propose criteria to assess the significance of individual FSH
      subunit or FSH dimer expression as well as genetic approaches to unambiguously
      define the physiological relevance of extra-pituitary FSH expression.

PMID- 29036568
TI  - Rhetoric of representation: the disempowerment and empowerment of consumer
      leaders.
AB  - Policy mandates consumer involvement in decisions at all levels of the mental
      health system. One barrier to this involvement is the expectation that consumers
      involved in systemic work represent broader consumer experiences. To examine how
      the rhetoric of 'representation' was used in relation to consumer involvement in
      mental health, a qualitative exploratory design was employed using interviews for
      data collection. Participants were consumers (n = 6) working with public or
      private mental health organizations in Australia, and colleagues (n = 3) or
      managers (n = 5) of these consumers. Discursive psychological principles informed
      the analytic process, to explore contexts in which 'representativeness' was used
      to empower and disempower consumers. The findings suggest there is a lack of
      clarity about what is meant by representation in the mental health sector.
      Expecting individual consumer leaders to be representative of consumer views more
      broadly disempowered them in their roles. Some participants instead discussed
      ways that organizations should be responsible for seeking representation from
      more consumer leaders, thus empowering consumers working in the sector. Using the
      term 'representative' to refer to consumers working in mental health does not
      reflect the value of the consumer perspective and is not well understood within
      the sector. Comprehensive training should be provided so that mental health
      service providers are clear regarding the expectations of people in these roles.

PMID- 29036566
TI  - The Role of Alternative Splicing and Differential Gene Expression in Cichlid
      Adaptive Radiation.
AB  - Species diverge eco-morphologically through the continuous action of natural
      selection on functionally important structures, producing alternative adaptive
      morphologies. In cichlid fishes, the oral and pharyngeal jaws are such key
      structures. Adaptive variation in jaw morphology contributes to trophic
      specialization, which is hypothesized to fuel their rapid speciation in the East
      African Great Lakes. Much is known about the genes involved in cichlid jaw and
      craniofacial development. However, it is still unclear what salient sources of
      variation gave rise to trophic-niche specialization, facilitating adaptive
      radiation. Here, we explore two sources of transcriptional variation that may
      underlie species-specific disparities in jaw morphology. Using whole
      transcriptome RNA-sequencing, we analyze differences in gene expression and
      alternative splicing, at the end of postlarval development, in fully functional
      jaws of six species of cichlids from the Lake Tanganyika tribe Tropheini. Our
      data reveal a surprisingly high degree of alternative splicing events compared
      with gene expression differences among species and trophic types. This suggests
      that differential trophic adaptation of the jaw apparatus may have been shaped by
      transcriptional rewiring of splicing as well as gene expression variation during
      the rapid radiation of the Tropheini. Specifically, genes undergoing splicing
      across most species were found to be enriched for pharyngeal jaw gene ontology
      terms. Overall, jaw transcriptional patterns at postlarval developmental stage
      were highly dynamic and species-specific. In conclusion, this work indicates that
      shifts in alternative splicing could have played a more important role in cichlid
      adaptive radiation, and possibly adaptive radiation in general, than currently
      recognized.

PMID- 29036570
TI  - Radon in the Exhaled Air of Patients in Radon Therapy.
AB  - In the Gastein valley, numerous facilities use radon for the treatment of various
      diseases either by exposure to radon in air or in radon rich thermal water. In
      this study, six test persons were exposed to radon thermal water in a bathtub and
      the time-dependent radon activity concentration in the exhaled air was recorded.
      At temperatures between 38 degrees C and 40 degrees C, the radon activity
      concentration in the water was about 900 kBq/m3 in a total volume of 600 l, where
      the patients were exposed for 20 min, while continuously sampling the exhaled air
      during the bathing and 20 min thereafter. After entering the bath, the exhaled
      radon activity concentration rapidly increased, reaching some kind of saturation
      after 20 min exposure. The radon activity concentration in the exhaled air was
      about 8000 Bq/m3 at the maximum, with higher concentrations for male test
      persons. The total radon transfer from water to the exhaled air was between 480
      and 1000 Bq, which is equivalent to 0.08% and 0.2% of the radon in the water.

PMID- 29036569
TI  - Opportunities for Epidemiologists in Implementation Science: A Primer.
AB  - The field of epidemiology has been defined as the study of the spread and control
      of disease. However, epidemiology frequently focuses on studies of etiology and
      distribution of disease at the cost of understanding the best ways to control
      disease. Moreover, only a small fraction of scientific discoveries are translated
      into public health practice, and the process from discovery to translation is
      exceedingly slow. Given the importance of translational science, the future of
      epidemiologic training should include competency in implementation science, whose
      goal is to rapidly move evidence into practice. Our purpose in this paper is to
      provide epidemiologists with a primer in implementation science, which includes
      dissemination research and implementation research as defined by the National
      Institutes of Health. We describe the basic principles of implementation science,
      highlight key components for conducting research, provide examples of
      implementation studies that encompass epidemiology, and offer resources and
      opportunities for continued learning. There is a clear need for greater speed,
      relevance, and application of evidence into practice, programs, and policies and
      an opportunity to enable epidemiologists to conduct research that not only will
      inform practitioners and policy-makers of risk but also will enhance the
      likelihood that evidence will be implemented.

PMID- 29036571
TI  - Atrial flow dynamics as a determinant of tissue temperature during balloon
      cryoablation.
AB  - Aims: Balloon cryoablation is an accepted method of achieving pulmonary vein
      isolation for the treatment of atrial fibrillation. The relationship between
      blood flow in the atrium and cryo energy delivery to the tissue remains poorly
      understood. Methods and results: Controlled cryoablations were performed in vitro
      using a pulmonary vein phantom constructed from bovine muscle, providing a 20 mm
      vein ostium. A temperature sensor was mounted within the 'vein wall' at a 1 mm
      tissue depth. Apparatus was constructed to assess the effect of incomplete
      pulmonary venous occlusion causing a leak, simulated atrial stasis, atrial
      circulation, and mitral regurgitation. Controlled ablations using the 2nd
      generation 28 mm cryoballoon catheter were repeated three times and mean values
      compared. Leak volume significantly affected both balloon temperatures and tissue
      temperatures. Simulated mitral regurgitation (MR) significantly impaired the
      effectiveness of cryo energy delivery resulting in significantly warmer balloon
      and tissue temperatures. With high leak volumes and moderate to severe MR there
      was a marked disparity between the cryoballoon temperature and the tissue
      temperature of approximately 60 degrees. Balloon warming times varied inversely
      with both leak volume and simulated MR flow volume. Conclusion: Incomplete venous
      occlusion and MR result in warmer balloon and tissue temperatures, and shorter
      balloon warming times, and are likely to significantly impair the effectiveness
      of cryoablation. Balloon temperature is poor indicator of tissue temperature
      under higher flow conditions.

PMID- 29036572
TI  - DOSE EFFECT OF THE 33S(n,alpha) 30SI REACTION IN BNCT USING THE NEW n_TOF-CERN
      DATA.
AB  - 33S is a stable isotope of sulphur which is being studied as a potential
      cooperative target for Boron Neutron Capture Therapy (BNCT) in accelerator-based
      neutron sources because of its large (n,alpha) cross section in the epithermal
      neutron energy range. Previous measurements resolved the resonances with a
      discrepant description of the lowest-lying and strongest one (at 13.5 keV).
      However, the evaluations of the major databases do not include resonances, except
      EAF-2010 which shows smaller values in this range than the experimental data.
      Furthermore, the glaring lack of data below 10 keV down to thermal (25.3 meV) has
      motivated a new measurement at n_TOF at CERN in order to cover the whole energy
      range. The inclusion of this new 33S(n,alpha) cross section in Monte Carlo
      simulations provides a more accurate estimation of the deposited kerma rate in
      tissue due to the presence of 33S. The results of those simulations represent the
      goal of this work.

PMID- 29036573
TI  - ComplexViewer: visualization of curated macromolecular complexes.
AB  - Summary: Proteins frequently function as parts of complexes, assemblages of
      multiple proteins and other biomolecules, yet network visualizations usually only
      show proteins as parts of binary interactions. ComplexViewer visualizes
      interactions with more than two participants and thereby avoids the need to first
      expand these into multiple binary interactions. Furthermore, if binding regions
      between molecules are known then these can be displayed in the context of the
      larger complex. Availability and implementation: freely available under Apache
      version 2 license; EMBL-EBI Complex Portal: http://www.ebi.ac.uk/complexportal;
      Source code: https://github.com/MICommunity/ComplexViewer; Package:
      https://www.npmjs.com/package/complexviewer; http://biojs.io/d/complexviewer.
      Language: JavaScript; Web technology: Scalable Vector Graphics; Libraries: D3.js.
      Contact: colin.combe@ed.ac.uk or juri.rappsilber@ed.ac.uk.

PMID- 29036574
TI  - Differential Expression of Hypertensive Phenotypes in BXD Mouse Strains in
      Response to Angiotensin II.
AB  - BACKGROUND: Besides environmental risk factors, genetic factors play a crucial
      role in the pathogenesis of primary hypertension. The current study is to unravel
      whether hypertensive phenotypes vary in mice with different genetic background.
      METHODS: Hypertension was induced in C57BL/6J (B6), DBA/2J (D2), and 25 BXD
      strains by administrating angiotensin (Ang)II (2.5 mg/kg/day infused by osmotic
      minipump) for 4 weeks. Systolic blood pressure was monitored before (baseline)
      and after 4 weeks of AngII treatment by tail cuff. Cardiac and renal fibrosis was
      evaluated by picrosirius red staining and collagen volume fraction (CVF) was
      quantitated using imaging analyzing system; cardiac transforming growth factor
      (TGF)-beta gene expression was monitored by RT-PCR, and inflammatory response was
      detected by immunohistochemical ED-1 staining. RESULTS: AngII infusion caused
      hypertension in all strains. However, blood pressure elevation was more evident
      in the D2 strain than the B6 group, while it was widely variable among BXD
      strains. Furthermore, chronic AngII treatment lead to development of hypertensive
      cardiac and renal diseases. Cardiac and renal CVF levels in the D2 strain was
      significantly higher than the B6 cohort, whereas these varied vastly across BXD
      strains. Moreover, cardiac TGF-beta mRNA levels were markedly diverse among
      various mouse strains. CONCLUSION: Our study unequivocally demonstrates that in
      response to AngII, BXDs with different genetic background expressed hypertension
      phenotypes with varied degree in severity. It implicates that genomics contribute
      to pathogenesis of primary hypertension. Building upon the genotype and
      hypertensive phenotypes, the BXD cohort can be further exploited experimentally
      to identify genes that influence blood pressure.

PMID- 29036575
TI  - Peptides of the variable IgG domain as potential biomarker candidates in primary
      open-angle glaucoma (POAG).
AB  - Autoantibody profiling has gained increasing interest in the research field of
      glaucoma promising the detection of highly specific and sensitive marker
      candidates for future diagnostic purposes. Recent studies demonstrated that
      immune responses are characterized by the expression of congruent or similar
      complementarity determining regions (CDR) in different individuals and could be
      used as molecular targets in biomarker discovery. Main objective of this study
      was to characterize glaucoma-specific peptides from the variable region of sera
      derived immunoglobulins using liquid chromatography--mass spectrometry (LC-MS)
      based quantitative proteomics. IgG was purified from sera of 13 primary open
      angle glaucoma patients (POAG) and 15 controls (CTRL) and subsequently digested
      into Fab and Fc by papain. Fab was further purified, tryptic digested and
      measured by LC-MS/MS. Discovery proteomics revealed in total 75 peptides of the
      variable IgG domain showing significant glaucoma-related level changes (P < 0.05;
      log2 fold change >= 0.5): 6 peptides were high abundant in POAG sera, whereas 69
      peptides were low abundant in comparison to CTRL group. Via accurate inclusion
      mass screening strategy 28 IgG V domain peptides were further validated showing
      significantly decreased expression levels in POAG sera. Amongst others 5 CDR1, 2
      CDR2 and 1 CDR3 sequences. In addition, we observed significant shifts in the
      variable heavy chain family distribution and disturbed kappa/lambda ratios in
      POAG patients in contrast to CTRL. These findings strongly indicate that glaucoma
      is accompanied by systemic effects on antibody production and B cell maturation
      possibly offering new prospects for future diagnostic or therapy purposes.

PMID- 29036576
TI  - cuRRBS: simple and robust evaluation of enzyme combinations for reduced
      representation approaches.
AB  - DNA methylation is an important epigenetic modification in many species that is
      critical for development, and implicated in ageing and many complex diseases,
      such as cancer. Many cost-effective genome-wide analyses of DNA modifications
      rely on restriction enzymes capable of digesting genomic DNA at defined sequence
      motifs. There are hundreds of restriction enzyme families but few are used to
      date, because no tool is available for the systematic evaluation of restriction
      enzyme combinations that can enrich for certain sites of interest in a genome.
      Herein, we present customised Reduced Representation Bisulfite Sequencing
      (cuRRBS), a novel and easy-to-use computational method that solves this problem.
      By computing the optimal enzymatic digestions and size selection steps required,
      cuRRBS generalises the traditional MspI-based Reduced Representation Bisulfite
      Sequencing (RRBS) protocol to all restriction enzyme combinations. In addition,
      cuRRBS estimates the fold-reduction in sequencing costs and provides a robustness
      value for the personalised RRBS protocol, allowing users to tailor the protocol
      to their experimental needs. Moreover, we show in silico that cuRRBS-defined
      restriction enzymes consistently out-perform MspI digestion in many biological
      systems, considering both CpG and CHG contexts. Finally, we have validated the
      accuracy of cuRRBS predictions for single and double enzyme digestions using two
      independent experimental datasets.

PMID- 29036578
TI  - The roles of membranes and associated cytoskeleton in plant virus replication and
      cell-to-cell movement.
AB  - The infection of plants by viruses depends on cellular mechanisms that support
      the replication of the viral genomes, and the cell-to-cell and systemic movement
      of the virus via plasmodesmata (PD) and the connected phloem. While the
      propagation of some viruses requires the conventional endoplasmic reticulum (ER)
      Golgi pathway, others replicate and spread between cells in association with the
      ER and are independent of this pathway. Using selected viruses as examples, this
      review re-examines the involvement of membranes and the cytoskeleton during virus
      infection and proposes potential roles of class VIII myosins and membrane
      tethering proteins in controlling viral functions at specific ER subdomains, such
      as cortical microtubule-associated ER sites, ER-plasma membrane contact sites,
      and PD.

PMID- 29036579
TI  - HybridSim-VS: a web server for large-scale ligand-based virtual screening using
      hybrid similarity recognition techniques.
AB  - Summary: Molecular-similarity searches based on two-dimensional (2D) fingerprint
      and three-dimensional (3D) shape represent two widely used ligand-based virtual
      screening (VS) methods in computer-aided drug design. 2D fingerprint-based VS
      utilizes the binary fragment information on a known ligand, whereas 3D shape
      based VS takes advantage of geometric information for predefined features from a
      3D conformation. Given their different advantages, it would be desirable to
      hybridize 2D fingerprint and 3D shape molecular-similarity approaches in drug
      discovery. Here, we presented a general hybrid molecular-similarity protocol,
      referred to as HybridSim, obtained by combining the 2D fingerprint- and 3D shape
      based similarity search methods and evaluated its performance on 595,036 actives
      and decoys for 40 pharmaceutically relevant targets available in the Directory of
      Useful Decoys Enhanced (DUD-E). Our results showed that HybridSim significantly
      improved the overall performance in 40 VS projects as compared with using only 2D
      fingerprint and 3D shape methods. Furthermore, HybridSim-VS, the first online
      platform using the proposed HybridSim method coupled with 17,839,945 screenable
      and purchasable compounds, was developed to provide large-scale and proficient VS
      capabilities to experts and nonexperts in the field. Availability and
      implementation: HybridSim-VS web server is freely available at
      http://www.rcidm.org/HybridSim-VS/. Contact: lingwang@scut.edu.cn. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29036577
TI  - BiobankUniverse: automatic matchmaking between datasets for biobank data
      discovery and integration.
AB  - Motivation: Biobanks are indispensable for large-scale genetic/epidemiological
      studies, yet it remains difficult for researchers to determine which biobanks
      contain data matching their research questions. Results: To overcome this, we
      developed a new matching algorithm that identifies pairs of related data elements
      between biobanks and research variables with high precision and recall. It
      integrates lexical comparison, Unified Medical Language System ontology tagging
      and semantic query expansion. The result is BiobankUniverse, a fast matchmaking
      service for biobanks and researchers. Biobankers upload their data elements and
      researchers their desired study variables, BiobankUniverse automatically
      shortlists matching attributes between them. Users can quickly explore matching
      potential and search for biobanks/data elements matching their research. They can
      also curate matches and define personalized data-universes. Availability and
      implementation: BiobankUniverse is available at http://biobankuniverse.com or can
      be downloaded as part of the open source MOLGENIS suite at
      http://github.com/molgenis/molgenis. Contact: m.a.swertz@rug.nl. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29036580
TI  - Time to epinephrine and survival after paediatric out-of-hospital cardiac arrest.
AB  - Aims: Delay in administration of epinephrine is associated with decreased
      survival among children with in-hospital cardiac arrest with an initial non
      shockable rhythm. Whether this association is applicable to paediatric out-of
      hospital cardiac arrest (OHCA) population remains unknown. We aimed to determine
      whether time to epinephrine administration is associated with outcomes in
      paediatric OHCA. Methods and results: This was a nation-wide population-based
      study of paediatric OHCA in Japan from 2005 to 2012 based on data from the All
      Japan Utstein Registry. We included paediatric OHCA patients (aged between 1 and
      17 years) who received at least one dose of epinephrine. The primary outcome was
      30-day survival. A total of 225 patients were included in the final cohort. Among
      the 225 patients, 23 (10.2%) survived 30 days after OHCA. The median time from
      emergency call to first epinephrine administration was 26 min [interquartile
      range, 20-32; range, 9-128; mean (standard deviation), 28.7 (15.5) min]. Longer
      time to epinephrine administration was associated with decreased chance of
      survival: 50.0, 41.2, 13.0, 11.6, 3.9, and 3.1%, respectively, when time to
      epinephrine was treated as a categorical variable categorized into <=10, 11-15,
      16-20, 21-25, 26-30, or > 30 min (P for trend <0.0001), and adjusted odds ratio
      0.90 (95% confidence interval 0.82-0.96, P = 0.0011) when time to epinephrine was
      treated as a linear and continuous variable in a multivariable logistic
      regression model. Similar trends were observed for prehospital return of
      spontaneous circulation (P = 0.0032) and neurologically favourable survival (P =
      0.0014). Conclusions: Among paediatric OHCA patients, delayed administration of
      epinephrine was associated with a decreased chance of favourable outcomes.

PMID- 29036581
TI  - Secondary use of electronic health record data for clinical workflow analysis.
AB  - Objective: Outpatient clinics lack guidance for tackling modern efficiency and
      productivity demands. Workflow studies require large amounts of timing data that
      are prohibitively expensive to collect through observation or tracking devices.
      Electronic health records (EHRs) contain a vast amount of timing data -
      timestamps collected during regular use - that can be mapped to workflow steps.
      This study validates using EHR timestamp data to predict outpatient ophthalmology
      clinic workflow timings at Oregon Health and Science University and demonstrates
      their usefulness in 3 different studies. Materials and Methods: Four outpatient
      ophthalmology clinics were observed to determine their workflows and to time each
      workflow step. EHR timestamps were mapped to the workflow steps and validated
      against the observed timings. Results: The EHR timestamp analysis produced times
      that were within 3 min of the observed times for >80% of the appointments. EHR
      use patterns affected the accuracy of using EHR timestamps to predict workflow
      times. Discussion: EHR timestamps provided a reasonable approximation of workflow
      and can be used for workflow studies. They can be used to create simulation
      models, analyze EHR use, and quantify the impact of trainees on workflow.
      Conclusion: The secondary use of EHR timestamp data is a valuable resource for
      clinical workflow studies. Sample timestamp data files and algorithms for
      processing them are provided and can be used as a template for more studies in
      other clinical specialties and settings.

PMID- 29036582
TI  - CHARACTERIZATION OF CLYC SCINTILLATOR COUPLED WITH PHOTOMULTIPLIERS AND A LARGE
      SIPM ARRAY.
AB  - CERN Radiation Protection group has recently developed a novel radiation survey
      meter called B-RAD able to operate in the presence of a strong magnetic field.
      The B-RAD will be equipped with a series of probes for gamma dose rate, gamma
      spectrometry and surface contamination measurements. The feasibility of
      developing a probe for neutron dose rate and possibly spectral measurements is
      being investigated. The determination of the breakdown voltage of the SiPM as
      well as its uniformity between the pixels was performed. The energy resolution of
      the Cs2LiYCl6:Ce (CLYC) scintillator was measured with the SiPM and compared with
      two different PMT models: Bialkali and Superbialkali. The temperature sensitivity
      of the system CLYC + SiPM was measured from -10 to + 40 degrees C.

PMID- 29036583
TI  - Characterization of moss ent-kaurene oxidase (CYP701B1) using a highly purified
      preparation.
AB  - CYP701B1 of the moss, Physcomitrella patents, might be a unique cytochrome P450
      having the ent-kaurene oxidase (KO) activity occurring in nonvascular plant.
      Phylogenetic analysis suggested that the gene encoding CYP701B1 was diverged from
      a common ancestral gene encoding KO of vascular plants. CYP701B1 expressed in
      Phichia yeast microsomes was purified and characterized. The purified CYP701B1
      catalyzed the oxidation of ent-kaurene to ent-kaurenoic acid through three
      successive monooxygenations, and the rate-limiting step of this oxidation might
      be the initial step that forms ent-kaurenol. CYP701B1 was a typical ferric low
      spin cytochrome P450 and was completely moved to high-spin state upon binding
      with ent-kaurene, and apparent Kd of ent-kaurene estimated by the spectral change
      caused by this spin-state shift was 2.5 MUM. The potent KO inhibitor uniconazole,
      an azole compound with molecular size similar to ent-kaurene, bound CYP701B1 with
      high affinity. However, ketoconazole, an azole compound whose molecular size is
      larger than ent-kaurene could not bind to CYP701B, though it binds strongly with
      CYP51, lanosterol 14-demethylase. The results indicated that the active site of
      CYP701B1 is fitted for the molecular size of ent-kaurene. The P450 monooxygenase
      adapted for ent-kaurene oxidation might appear in land plants before evolutionary
      divergence into vascular and nonvascular plants.

PMID- 29036584
TI  - cgHeliParm: analysis of dsDNA helical parameters for coarse-grained MARTINI
      molecular dynamics simulations.
AB  - Summary: We introduce cgHeliParm, a python program that provides the
      conformational analysis of Martini-based coarse-grained double strand DNA
      molecules. The software calculates the helical parameters such as base, base pair
      and base pair step parameters. cgHeliParm can be used for the analysis of coarse
      grain Martini molecular dynamics trajectories without transformation into
      atomistic models. Availability and implementation: This package works with Python
      2.7 on MacOS and Linux. The program is freely available for download from
      https://github.com/ifaust83/cgheliparm. Together with the main script, the base
      reference files CG_X_std.lib, a number of examples and R scripts are also
      available from the same website. A tutorial on the use and application is also
      available at http://cgmartini.nl/index.php/tutorials-general
      introduction/tutorial-martini-dna. Contact: i.faustino@rug.nl. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29036585
TI  - Ambulatory pH-impedance-pressure monitoring as a diagnostic tool for the reflux
      cough syndrome.
AB  - Gastroesophageal reflux is considered to be a significant contributing factor to
      chronic unexplained cough. Patients are often presumed to have reflux-induced
      cough and are exposed to high-dose and long-term empirical therapy with proton
      pump inhibitors (PPIs) despite the limited treatment efficacy in this population.
      We aimed to assess the diagnostic value of 24-hour ambulatory pH-impedance
      pressure monitoring for the diagnosis of reflux-induced chronic cough. In this
      multicenter study, we evaluated 192 patients with chronic cough using 24-hour pH
      impedance-pressure monitoring off PPIs. Manometry was used to detect all cough
      bursts while pH-impedance allowed for the evaluation of all reflux episodes,
      including weakly acidic reflux. The symptom association probability was used to
      determine a temporal relationship between reflux and cough. A diagnosis of reflux
      induced cough was made in 25.5% of the patients. If only acid reflux episodes
      were used, 22.4% of those patients would not have been diagnosed. Significantly
      more patients with reflux-induced cough had typical reflux symptoms (P = 0.031)
      and a pathological distal acid exposure time (P = 0.025) in comparison to
      patients without the diagnosis. A diagnosis of cough-induced reflux was made in
      24.0% of the patients. Only 59% of all cough bursts were registered by the
      patients. Overall, only approximately one quarter of patients with chronic
      unexplained cough have reflux-induced cough, explaining the observation that the
      vast majority of patients with chronic cough do not benefit from antireflux
      therapy. pH-impedance-pressure monitoring helps to identify patients who are
      likely to have reflux as a cause of their chronic cough.

PMID- 29036586
TI  - Epigenetic mechanisms underlie the crosstalk between growth factors and a steroid
      hormone.
AB  - Crosstalk between growth factors (GFs) and steroid hormones recurs in
      embryogenesis and is co-opted in pathology, but underlying mechanisms remain
      elusive. Our data from mammary cells imply that the crosstalk between the
      epidermal GF and glucocorticoids (GCs) involves transcription factors like p53
      and NF-kappaB, along with reduced pausing and traveling of RNA polymerase II
      (RNAPII) at both promoters and bodies of GF-inducible genes. Essentially, GCs
      inhibit positive feedback loops activated by GFs and stimulate the reciprocal
      inhibitory loops. As expected, no alterations in DNA methylation accompany the
      transcriptional events instigated by either stimulus, but forced demethylation of
      regulatory regions broadened the repertoire of GF-inducible genes. We report that
      enhancers, like some promoters, are poised for activation by GFs and GCs. In
      addition, within the cooperative interface of the crosstalk, GFs enhance binding
      of the GC receptor to DNA and, in synergy with GCs, promote productive RNAPII
      elongation. Reciprocally, within the antagonistic interface GFs hyper-acetylate
      chromatin at unmethylated promoters and enhancers of genes involved in motility,
      but GCs hypoacetylate the corresponding regions. In conclusion, unmethylated
      genomic regions that encode feedback regulatory modules and differentially
      recruit RNAPII and acetylases/deacetylases underlie the crosstalk between GFs and
      a steroid hormone.

PMID- 29036587
TI  - Latent Profile Analysis and Conversion to Psychosis: Characterizing Subgroups to
      Enhance Risk Prediction.
AB  - BACKGROUND: Groups at clinical high risk (CHR) of developing psychosis are
      heterogeneous, composed of individuals with different clusters of symptoms. It is
      likely that there exist subgroups, each associated with different symptom
      constellations and probabilities of conversion. METHOD: Present study used latent
      profile analysis (LPA) to ascertain subgroups in a combined sample of CHR (n =
      171) and help-seeking controls (HSCs; n = 100; PREDICT study). Indicators in the
      LPA model included baseline Scale of Prodromal Symptoms (SOPS), Calgary
      Depression Scale for Schizophrenia (CDSS), and neurocognitive performance as
      measured by multiple instruments, including category instances (CAT). Subgroups
      were further characterized using covariates measuring demographic and clinical
      features. RESULTS: Three classes emerged: class 1 (mild, transition rate 5.6%),
      lowest SOPS and depression scores, intact neurocognitive performance; class 2
      (paranoid-affective, transition rate 14.2%), highest suspiciousness, mild
      negative symptoms, moderate depression; and class 3 (negative-neurocognitive,
      transition rate 29.3%), highest negative symptoms, neurocognitive impairment,
      social cognitive impairment. Classes 2 and 3 evidenced poor social functioning.
      CONCLUSIONS: Results support a subgroup approach to research, assessment, and
      treatment of help-seeking individuals. Class 3 may be an early risk stage of
      developing schizophrenia.

PMID- 29036589
TI  - Simultaneous Determination of 11 High-Polarity Components from Fructus Corni: A
      Quantitative LC-MS/MS Method for Improved Quality Control.
AB  - Fructus Corni, the dried ripe sarcocarp of Cornus officinalis Sieb.et Zucc
      (Cornaceae), is widely used in traditional medicine. Pharmacological studies to
      date have attributed many biological effects to the high-polarity components.
      However, current quality control methods focus on only several iridoid glycoside
      components, and, of note, there is no comprehensive method available to
      simultaneously quantify the high-polarity components in Fructus Corni. Here, a
      simple, sensitive and robust liquid chromatography-electrospray ionization-tandem
      mass spectrometry method was developed to simultaneously determine 11 high
      polarity constituents (5-hydroxymethyl-2-furfural, gallic acid, sweroside,
      cornin, loganin, morroniside, 7alpha-O-methylmorroniside, 7beta-O
      methylmorroniside, 7alpha-O-ethylmorroniside and 7beta-O-ethylmorroniside,
      cornuside) of Fructus Corni. This method showed good specificity, linearity (r2
      >= 0.9907), repeatability (RSD < 5.98%) and recovery (93.24 ~ 112.92%, RSD <
      9.06%). This validated method was successfully employed to assess the component
      variation of crude Fructus Corni of three regional origins as well as after
      processing. In particular, the iridoid isomers were, for the first time, included
      as the quality markers for Fructus Corni. We propose that this method may provide
      a new and powerful tool for achieving comprehensive quality control of Fructus
      Corni.

PMID- 29036588
TI  - A novel data structure to support ultra-fast taxonomic classification of
      metagenomic sequences with k-mer signatures.
AB  - Motivation: Metagenomic read classification is a critical step in the
      identification and quantification of microbial species sampled by high-throughput
      sequencing. Although many algorithms have been developed to date, they suffer
      significant memory and/or computational costs. Due to the growing popularity of
      metagenomic data in both basic science and clinical applications, as well as the
      increasing volume of data being generated, efficient and accurate algorithms are
      in high demand. Results: We introduce MetaOthello, a probabilistic hashing
      classifier for metagenomic sequencing reads. The algorithm employs a novel data
      structure, called l-Othello, to support efficient querying of a taxon using its k
      mer signatures. MetaOthello is an order-of-magnitude faster than the current
      state-of-the-art algorithms Kraken and Clark, and requires only one-third of the
      RAM. In comparison to Kaiju, a metagenomic classification tool using protein
      sequences instead of genomic sequences, MetaOthello is three times faster and
      exhibits 20-30% higher classification sensitivity. We report comparative analyses
      of both scalability and accuracy using a number of simulated and empirical
      datasets. Availability and implementation: MetaOthello is a stand-alone program
      implemented in C ++. The current version (1.0) is accessible via
      https://doi.org/10.5281/zenodo.808941. Contact: liuj@cs.uky.edu. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29036590
TI  - TissGDB: tissue-specific gene database in cancer.
AB  - Tissue-specific gene expression is critical in understanding biological
      processes, physiological conditions, and disease. The identification and
      appropriate use of tissue-specific genes (TissGenes) will provide important
      insights into disease mechanisms and organ-specific therapeutic targets. To
      better understand the tissue-specific features for each cancer type and to
      advance the discovery of clinically relevant genes or mutations, we built TissGDB
      (Tissue specific Gene DataBase in cancer) available at
      http://zhaobioinfo.org/TissGDB. We collected and curated 2461 tissue specific
      genes (TissGenes) across 22 tissue types that matched the 28 cancer types of The
      Cancer Genome Atlas (TCGA) from three representative tissue-specific gene
      expression resources: The Human Protein Atlas (HPA), Tissue-specific Gene
      Expression and Regulation (TiGER), and Genotype-Tissue Expression (GTEx). For
      these 2461 TissGenes, we performed gene expression, somatic mutation, and
      prognostic marker-based analyses across 28 cancer types using TCGA data. Our
      analyses identified hundreds of TissGenes, including genes that universally kept
      or lost tissue-specific gene expression, with other features: cancer type
      specific isoform expression, fusion with oncogenes or tumor suppressor genes, and
      markers for protective or risk prognosis. TissGDB provides seven categories of
      annotations: TissGeneSummary, TissGeneExp, TissGene-miRNA, TissGeneMut,
      TissGeneNet, TissGeneProg, TissGeneClin.

PMID- 29036591
TI  - PLACNETw: a web-based tool for plasmid reconstruction from bacterial genomes.
AB  - Summary: PLACNET is a graph-based tool for reconstruction of plasmids from next
      generation sequence pair-end datasets. PLACNET graphs contain two types of nodes
      (assembled contigs and reference genomes) and two types of edges (scaffold links
      and homology to references). Manual pruning of the graphs is a necessary
      requirement in PLACNET, but this is difficult for users without solid
      bioinformatic background. PLACNETw, a webtool based on PLACNET, provides an
      interactive graphic interface, automates BLAST searches, and extracts the
      relevant information for decision making. It allows a user with domain expertise
      to visualize the scaffold graphs and related information of contigs as well as
      reference sequences, so that the pruning operations can be done interactively
      from a personal computer without the need for additional tools. After successful
      pruning, each plasmid becomes a separate connected component subgraph. The
      resulting data are automatically downloaded by the user. Availability and
      implementation: PLACNETw is freely available at
      https://castillo.dicom.unican.es/upload/. Contact: delacruz@unican.es.
      Supplementary information: A tutorial video and several solved examples are
      available at https://castillo.dicom.unican.es/placnetw_video/ and
      https://castillo.dicom.unican.es/examples/.

PMID- 29036593
TI  - EELS at very high energy losses.
AB  - Electron energy-loss spectroscopy (EELS) has been investigated in the range from
      2 to >10 keV using an optimized optical coupling of the microscope to the
      spectrometer to improve the high loss performance in EELS. It is found that
      excellent quality data can now be acquired up until about 5 keV, suitable for
      both energy loss near edge structure (ELNES) studies of oxidation and local
      chemistry, and potentially useful for extended energy loss fine structure
      (EXELFS) studies of local atomic ordering. Examples studied included oxidation in
      Zr, Mo and Sn, and the ELNES and EXELFS of the Ti-K edge. It is also shown that
      good quality electron energy-loss spectroscopy can even be performed for losses
      above 9.2 keV, the energy loss at which the collection angle becomes 'infinite',
      and this is demonstrated using the tungsten L3 edge at about 10.2 keV.

PMID- 29036592
TI  - Gain and Loss of Small RNA Classes-Characterization of Small RNAs in the
      Parasitic Nematode Family Strongyloididae.
AB  - The nematode family Strongyloididae is of particular interest because it contains
      important parasites of medical and veterinary relevance. In addition, species of
      this family can form parasitic and free-living generations and it also occupies
      an interesting phylogenetic position within the nematodes. Nematodes differ in
      several ways from other taxa with respect to their small noncoding RNAs. Recent
      comparative studies revealed that there is also considerable variability within
      the nematodes. However, no Strongyloididae species or close relative was included
      in these studies. We characterized the small RNAs of two developmental stages of
      three different Strongyloididae species and compared them with the well-studied
      free-living nematodes Caenorhabditis elegans and Pristionchus pacificus.
      Strongyloididae have conserved and taxon-specific microRNAs, many of which are
      differentially regulated between the two developmental stages. We identified a
      novel class of around 27-nucleotide-long RNAs starting with 5'G or A, of which a
      large fraction have the potential to target transposable elements. These RNAs
      most likely have triphosphates at their 5' ends and are therefore presumably
      synthesized by RNA-dependent RNA polymerases. In contrast to C. elegans but
      similarly to some other nematode taxa, Strongyloididae have no Piwi-interacting
      RNAs, nor do their genomes encode Argonaute proteins of the Piwi family. Finally,
      we attempted but failed to detect circulating parasite small RNAs in the blood of
      hosts.

PMID- 29036594
TI  - Impaired defense reactions in apple replant disease-affected roots of Malus
      domestica 'M26'.
AB  - A soil- and site-dependent complex of diverse microbial populations causes apple
      replant disease (ARD), which leads to economic losses for tree nurseries and
      apple producers due to reduced plant growth and diminished fruit yields. Soil
      fumigation has been widely used to mitigate ARD, but the application of these
      chemicals is restricted in the European Union. Hence, other counteractions have
      to be developed. Genomics-based breeding may be used to select ARD-tolerant
      genotypes; however, molecular responses of ARD are not well understood. Recent
      studies revealed that biotic stress-associated genes involved in typical defense
      reactions are activated but do not result in an adequate response to ARD. The
      objective of this study was to analyze selected responsive genes in a time-course
      experiment to test for expression kinetics. Cultivating the ARD-susceptible apple
      rootstock 'M26' on ARD-affected soil resulted in significantly reduced growth as
      early as 7 days after planting. Genes involved in phytoalexin biosynthesis were
      upregulated in ARD samples as early as 3 days after planting and reached up to 26
      fold changes at Day 10, which resulted in high amounts of 3-hydroxy-5
      methoxybiphenyl, aucuparin, noraucuparin, 2-hydroxy-4-methoxydibenzofuran, 2'
      hydroxyaucuparin and noreriobofuran. For the first time, these phytoalexins were
      detected, identified and quantified in apple roots. The lack of a sufficient
      defense response may be due to impaired sequestration and/or exudation of the
      potentially cytotoxic phytoalexins and perturbed formation of reactive oxygen
      species, leading to root damage in ARD soils. The findings provide a basis for
      comparative studies of the defense processes in more ARD-tolerant rootstocks.

PMID- 29036595
TI  - Persistent in vivo cytogenetic effects of radioiodine therapy: a 21-year follow
      up study using multicolor FISH.
AB  - Our previous studies demonstrated the cytogenetic effects in the peripheral blood
      lymphocytes of a 34-year-old male patient who received ablative radioactive
      131iodine therapy (RIT) on two different occasions in 1992 and 1994. Assessment
      of RIT-induced chromosomal damage by the cytokinesis-blocked micronucleus assay
      (CBMN) showed the persistence of elevated micronucleus frequency in this patient
      for more than two decades since the first RIT. Subsequent cytogenetic analysis
      performed in 2012 revealed both stable and unstable aberrations, whose
      frequencies were higher than the baseline reported in the literature. Here, we
      report the findings of our recent cytogenetic analysis peformed in 2015 on this
      patient using the multicolor fluorescence in situ hybridization (mFISH)
      technique. Our results showed that both reciprocal and non-reciprocal
      translocations persisted at higher frequencies in the patient than those reported
      in 2012. Persistence of structural aberrations for more than two decades indicate
      that these aberrations might have originated from long-lived T-lymphocytes or
      hematopoietic stem cells. Our study suggests that the long-term persistence of
      chromosome translocations in circulating lymphocytes can be useful for monitoring
      the extent of RIT-induced chromosomal instability several years after exposure
      and for estimating the cumulative absorbed dose after multiple RITs for
      retrospective biodosimetry purposes. This is perhaps the first and longest follow
      up study documenting the persistence of cytogenetic damage for 21 years after
      internal radiation exposure.

PMID- 29036596
TI  - DelPhiForce web server: electrostatic forces and energy calculations and
      visualization.
AB  - Summary: Electrostatic force is an essential component of the total force acting
      between atoms and macromolecules. Therefore, accurate calculations of
      electrostatic forces are crucial for revealing the mechanisms of many biological
      processes. We developed a DelPhiForce web server to calculate and visualize the
      electrostatic forces at molecular level. DelPhiForce web server enables modeling
      of electrostatic forces on individual atoms, residues, domains and molecules, and
      generates an output that can be visualized by VMD software. Here we demonstrate
      the usage of the server for various biological problems including protein
      cofactor, domain-domain, protein-protein, protein-DNA and protein-RNA
      interactions. Availability and implementation: The DelPhiForce web server is
      available at: http://compbio.clemson.edu/delphi-force. Contact:
      delphi@clemson.edu. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29036597
TI  - Faucet: streaming de novo assembly graph construction.
AB  - Motivation: We present Faucet, a two-pass streaming algorithm for assembly graph
      construction. Faucet builds an assembly graph incrementally as each read is
      processed. Thus, reads need not be stored locally, as they can be processed while
      downloading data and then discarded. We demonstrate this functionality by
      performing streaming graph assembly of publicly available data, and observe that
      the ratio of disk use to raw data size decreases as coverage is increased.
      Results: Faucet pairs the de Bruijn graph obtained from the reads with additional
      meta-data derived from them. We show these metadata-coverage counts collected at
      junction k-mers and connections bridging between junction pairs-contain most
      salient information needed for assembly, and demonstrate they enable cleaning of
      metagenome assembly graphs, greatly improving contiguity while maintaining
      accuracy. We compared Fauceted resource use and assembly quality to state of the
      art metagenome assemblers, as well as leading resource-efficient genome
      assemblers. Faucet used orders of magnitude less time and disk space than the
      specialized metagenome assemblers MetaSPAdes and Megahit, while also improving on
      their memory use; this broadly matched performance of other assemblers optimizing
      resource efficiency-namely, Minia and LightAssembler. However, on metagenomes
      tested, Faucet,o outputs had 14-110% higher mean NGA50 lengths compared with
      Minia, and 2- to 11-fold higher mean NGA50 lengths compared with LightAssembler,
      the only other streaming assembler available. Availability and implementation:
      Faucet is available at https://github.com/Shamir-Lab/Faucet. Contact:
      rshamir@tau.ac.il or eranhalperin@gmail.com. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29036598
TI  - Global DNA methylation analysis reveals miR-214-3p contributes to cisplatin
      resistance in pediatric intracranial nongerminomatous malignant germ cell tumors.
AB  - Background: Pediatric central nervous system germ cell tumors (CNSGCTs) are rare
      and heterogeneous neoplasms, which can be divided into germinomas and
      nongerminomatous germ cell tumors (NGGCTs). NGGCTs are further subdivided into
      mature teratomas and nongerminomatous malignant GCTs (NGMGCTs). Clinical outcomes
      suggest that NGMGCTs have poor prognosis and survival and that they require more
      extensive radiotherapy and adjuvant chemotherapy. However, the mechanisms
      underlying this difference are still unclear. DNA methylation alteration is
      generally acknowledged to cause therapeutic resistance in cancers. We
      hypothesized that the pediatric NGMGCTs exhibit a different genome-wide DNA
      methylation pattern, which is involved in the mechanism of its therapeutic
      resistance. Methods: We performed methylation and hydroxymethylation DNA
      immunoprecipitation sequencing, mRNA expression microarray, and small RNA
      sequencing (smRNA-seq) to determine methylation-regulated genes, including
      microRNAs (miRNAs). Results: The expression levels of 97 genes and 8 miRNAs were
      correlated with promoter DNA methylation and hydroxymethylation status, such as
      the miR-199/-214 cluster, and treatment with DNA demethylating agent 5-aza-2'
      deoxycytidine elevated its expression level. Furthermore, smRNA-seq analysis
      showed 27 novel miRNA candidates with differential expression between germinomas
      and NGMGCTs. Overexpresssion of miR-214-3p in NCCIT cells leads to reduced
      expression of the pro-apoptotic protein BCL2-like 11 and induces cisplatin
      resistance. Conclusions: We interrogated the differential DNA methylation
      patterns between germinomas and NGMGCTs and proposed a mechanism for
      chemoresistance in NGMGCTs. In addition, our sequencing data provide a roadmap
      for further pediatric CNSGCT research and potential targets for the development
      of new therapeutic strategies.

PMID- 29036599
TI  - Carbon allocation and partitioning in Populus tremuloides are modulated by
      ectomycorrhizal fungi under phosphorus limitation.
AB  - The fate of carbon (C) captured by forest trees during photosynthesis is
      influenced by the supply of other resources. Fixed C may be partitioned among
      biomolecules within the leaf and/or allocated throughout the tree to growth,
      storage and maintenance activities. Phosphorus (P) availability often limits tree
      productivity due to its high biological demand and strong interactions with soil
      minerals. As ectomycorrhizal (ECM) fungi play critical roles in enhancing
      phosphate (Pi) acquisition by their hosts, these symbioses will influence the
      fate of C within trees and forested ecosystems. Using Populus tremuloides Michx.
      (trembling aspen) in symbiosis with Laccaria bicolor (Marie) P.D. Orton or
      Paxillus involutus (Batsch) Fr., we assessed C acquisition, allocation and
      partitioning under Pi limitation, specifically focusing on primary and secondary
      C compounds. Both ECM fungi moderated the effects of low P on photosynthesis and
      C partitioning among carbohydrates and secondary metabolites by sustaining Pi
      uptake and translocation in P. tremuloides under Pi limitation. As leaf P
      declined, reductions in photosynthesis were accompanied by significant shifts in
      C partitioning from nonstructural carbohydrates (NSCs) to phenolic glycosides and
      tannins. Carbon partitioning in roots exhibited more complex patterns, with
      distinct increases in NSCs in nonmycorrhizal (NM) plants under Pi limitation that
      were not evident in plants colonized by either ECM symbiont. In general, aspen
      colonized by L. bicolor exhibited C partitioning patterns intermediate between
      those of NM and P. involutus aspen. The C cost of symbiosis was pronounced for
      plants supporting P. involutus, where ECM plants exhibited maintenance of
      photosynthesis yet reduced biomass in comparison with NM and L. bicolor aspen
      under Pi replete conditions. Our results indicate that the ECM symbiosis affects
      the disposition of C in forest trees in part by altering the acquisition of other
      limiting resources from soils, but also through ECM species-specific influences
      on host physiology. This modulation of C partitioning will have broad
      implications for forest ecosystem C capture, storage and cycling where nutrient
      resources may be limited.

PMID- 29036600
TI  - Brain cancer cluster investigation around a factory emitting dichloromethane.
AB  - Background: The health risks associated with dichloromethane (DCM) for the
      general population living near industrial activities have not yet been
      quantified, primarily due to lack of epidemiological datasets. In the absence of
      such human data, we undertook a cancer cluster investigation in Cyprus around a
      historically using DCM plant producing shoe soles that were globally exported. We
      designed the methodology to investigate the possible existence of a cancer
      cluster in the area around the factory (point zero) and within a radius of 500
      meters. Methods: A retrospective comparative population study was designed using
      a group of cancer patients living or working in the chosen geographical area
      around the factory. Results: Mean stack emissions of DCM of 88 mg/Nm3 and flow
      rates of 850 g/h exceeded the permissible DCM limits established for industrial
      zones. Brain and central nervous system (CNS) cancer incidence rates showed
      significant (P < 0.001) increase in the study area around the plant when compared
      with those observed in other areas of Cyprus. Calculated standardized incidence
      ratios for brain/CNS after adjusting for the age at diagnosis ranged from 11.3
      25.7 [mean 6.5 (3.02 : 12.3)] for the study area. Conclusions: We showed the
      association between chronic, unintentional DCM exposures and brain/CNS cancer
      cases for the general population located in a residential area being in close
      proximity with a plant historically emitting DCM.

PMID- 29036601
TI  - Arrhythmogenic right ventricular cardiomyopathy: implications of next-generation
      sequencing and of miRNAs regulation in appropriate understanding and treatment.

PMID- 29036603
TI  - Identification of optimal reference genes for transcriptomic analyses in normal
      and diseased human heart.
AB  - Aims: Quantitative real-time RT-PCR (RT-qPCR) has become the method of choice for
      mRNA quantification, but requires an accurate normalization based on the use of
      reference genes showing invariant expression across various pathological
      conditions. Only few data exist on appropriate reference genes for the human
      heart. The objective of this study was to determine a set of suitable reference
      genes in human atrial and ventricular tissues, from right and left cavities in
      control and in cardiac diseases. Methods and results: We assessed the expression
      of 16 reference genes (ACTB, B2M, GAPDH, GUSB, HMBS, HPRT1, IPO8, PGK1, POLR2A,
      PPIA, RPLP0, TBP, TFRC, UBC, YWHAZ, 18S) in tissues from: right and left
      ventricles from healthy controls and heart failure (HF) patients; right-atrial
      tissue from patients in sinus rhythm with (SRd) or without (SRnd) atrial
      dilatation, patients with paroxysmal (pAF) or chronic (cAF) atrial fibrillation
      or with HF; and left-atrial tissue from patients in SR or cAF. Consensual
      analysis (by geNorm and Normfinder algorithms, BestKeeper software tool and
      comparative delta-Ct method) of the variability scores obtained for each
      reference gene expression shows that the most stably expressed genes are: GAPDH,
      GUSB, IPO8, POLR2A, and YWHAZ when comparing either right and left ventricle or
      ventricle from healthy controls and HF patients; GAPDH, IPO8, POLR2A, PPIA, and
      RPLP0 when comparing either right and left atrium or right atria from all
      pathological groups. ACTB, TBP, TFRC, and 18S genes were identified as the least
      stable. Conclusions: The overall most stable reference genes across different
      heart cavities and disease conditions were GAPDH, IPO8, POLR2A and PPIA. YWHAZ or
      GUSB could be added to this set for some specific experiments. This study should
      provide useful guidelines for reference gene selection in RT-qPCR studies in
      human heart.

PMID- 29036602
TI  - N6-adenine DNA methylation is associated with the linker DNA of H2A.Z-containing
      well-positioned nucleosomes in Pol II-transcribed genes in Tetrahymena.
AB  - DNA N6-methyladenine (6mA) is newly rediscovered as a potential epigenetic mark
      across a more diverse range of eukaryotes than previously realized. As a
      unicellular model organism, Tetrahymena thermophila is among the first eukaryotes
      reported to contain 6mA modification. However, lack of comprehensive information
      about 6mA distribution hinders further investigations into its function and
      regulatory mechanism. In this study, we provide the first genome-wide, base pair
      resolution map of 6mA in Tetrahymena by applying single-molecule real-time (SMRT)
      sequencing. We provide evidence that 6mA occurs mostly in the AT motif of the
      linker DNA regions. More strikingly, these linker DNA regions with 6mA are
      usually flanked by well-positioned nucleosomes and/or H2A.Z-containing
      nucleosomes. We also find that 6mA is exclusively associated with RNA polymerase
      II (Pol II)-transcribed genes, but is not an unambiguous mark for active
      transcription. These results support that 6mA is an integral part of the
      chromatin landscape shaped by adenosine triphosphate (ATP)-dependent chromatin
      remodeling and transcription.

PMID- 29036604
TI  - Accomplishing reform: successful case studies drawn from the health systems of 60
      countries.
AB  - Healthcare reform typically involves orchestrating a policy change, mediated
      through some form of operational, systems, financial, process or practice
      intervention. The aim is to improve the ways in which care is delivered to
      patients. In our book 'Health Systems Improvement Across the Globe: Success
      Stories from 60 Countries', we gathered case-study accomplishments from 60
      countries. A unique feature of the collection is the diversity of included
      countries, from the wealthiest and most politically stable such as Japan, Qatar
      and Canada, to some of the poorest, most densely populated or politically
      challenged, including Afghanistan, Guinea and Nigeria. Despite constraints faced
      by health reformers everywhere, every country was able to share a story of
      accomplishment-defining how their case example was managed, what services were
      affected and ultimately how patients, staff, or the system overall, benefited.
      The reform themes ranged from those relating to policy, care coverage and
      governance; to quality, standards, accreditation and regulation; to the
      organization of care; to safety, workforce and resources; to technology and IT;
      through to practical ways in which stakeholders forged collaborations and
      partnerships to achieve mutual aims. Common factors linked to success included
      the 'acorn-to-oak tree' principle (a small scale initiative can lead to system
      wide reforms); the 'data-to-information-to-intelligence' principle (the role of
      IT and data are becoming more critical for delivering efficient and appropriate
      care, but must be converted into useful intelligence); the 'many-hands' principle
      (concerted action between stakeholders is key); and the 'patient-as-the-pre
      eminent-player' principle (placing patients at the centre of reform designs is
      critical for success).

PMID- 29036605
TI  - Survey of laboratory practices for diagnosis of fungal infection in seven Asian
      countries: An Asia Fungal Working Group (AFWG) initiative.
AB  - An online survey of mycology laboratories in seven Asian countries was conducted
      to assess the status, competence, and services available. Country representatives
      from the Asia Fungal Working Group (AFWG) contacted as many laboratories
      performing mycology diagnosis as possible in their respective countries,
      requesting that the laboratory heads complete the online survey. In total, 241
      laboratories responded, including 71 in China, 104 in India, 11 in Indonesia, 26
      in the Philippines, four in Singapore, 18 in Taiwan, and seven in Thailand.
      Overall, 129/241 (53.5%) surveyed mycology laboratories operate as separate
      designated mycology laboratories, 75/241 (31.1%) conduct regular formal staff
      training, 103/241 (42.7%) are accredited, and 88/157 (56.1%) participate in
      external quality assurance scheme (EQAS) programs. Microscopy and culture methods
      are available in nearly all laboratories, although few perform DNA sequencing
      (37/219; 16.9%) or use matrix-assisted laser desorption/ionization time-of-flight
      mass spectroscopy (MALDI-TOF MS) (27/219; 12.3%) for isolate identification.
      Antifungal susceptibility testing is performed in 142/241 (58.9%) laboratories,
      mainly for yeasts. The most commonly performed nonculture diagnostic is
      cryptococcal antigen testing (66 laboratories), followed by galactomannan testing
      (55), polymerase chain reaction (PCR) diagnosis (37), and beta-D-glucan testing
      (24). Therapeutic drug monitoring is conducted in 21 laboratories. There is
      almost no access to advanced diagnostic tests, like galactomannan, beta-D-glucan,
      and PCR, in the surveyed laboratories in Indonesia, the Philippines, and
      Thailand. These results highlight the need for development of quality
      laboratories, accreditation and training of manpower in existing laboratories,
      and access to advanced non-culture-based diagnostic tests to facilitate the
      diagnosis of fungal infections in Asia.

PMID- 29036606
TI  - Socioeconomic Status and Childhood Cancer Incidence: A Population-Based
      Multilevel Analysis.
AB  - The etiology of childhood cancers remains largely unknown, especially regarding
      environmental and behavioral risk factors. Unpacking the association between
      socioeconomic status (SES) and incidence may offer insight into such etiology. We
      tested associations between SES and childhood cancer incidence in a population
      based case-cohort study (source cohort: Minnesota birth registry, 1989-2014).
      Cases, ages 0-14 years, were linked from the Minnesota Cancer Surveillance System
      to birth records through probabilistic record linkage. Controls were 4:1
      frequency matched on birth year (2,947 cases and 11,907 controls). We tested
      associations of individual-level (maternal education) and neighborhood-level
      (census tract composite index) SES using logistic mixed models. In crude models,
      maternal education was positively associated with incidence of acute
      lymphoblastic leukemia (odds ratio (OR) = 1.10, 95% confidence interval (CI):
      1.02, 1.19), central nervous system tumors (OR = 1.12, 95% CI: 1.04, 1.21), and
      neuroblastoma (OR = 1.15, 95% CI: 1.02, 1.30). Adjustment for established risk
      factors-including race/ethnicity, maternal age, and birth weight-substantially
      attenuated these positive associations. Similar patterns were observed for
      neighborhood-level SES. Conversely, higher maternal education was inversely
      associated with hepatoblastoma incidence (adjusted OR = 0.70, 95% CI: 0.51,
      0.98). Overall, beyond the social patterning of established demographic and
      pregnancy-related exposures, SES is not strongly associated with childhood cancer
      incidence.

PMID- 29036607
TI  - Endoscopic and histopathologic reflux-associated mucosal damage in the remnant
      esophagus following transthoracic esophagectomy for cancer-5-year long-term
      follow-up.
AB  - Gastroesophageal reflux is a common problem following esophagectomy and
      reconstruction with gastric interposition. Despite a routine prescription of
      proton pump inhibitors, reflux-associated mucosal damage in the remnant esophagus
      is frequently observed. Purpose of this study is to evaluate mucosal damage in
      the esophageal remnant during long-term follow-up and to compare the prevalence
      of this damage between the subgroups of esophageal squamous cell and
      adenocarcinoma. All patients undergoing transthoracic Ivor-Lewis esophagectomy
      were prospectively entered in our IRB approved database. All patients underwent a
      routine check-up program with yearly surveillance endoscopies following
      esophagectomy. Only patients with a complete follow-up were included into this
      study. Endoscopic and histopathologic mucosal changes of the remnant esophagus
      were analyzed in close intervals. A total of 50 patients met the inclusion
      criteria, consisting of 31 adenocarcinomas (AC) and 19 squamous cell carcinomas
      (SCC). Mucosal damage was already seen 1 year after surgery in 20 patients
      macroscopically (43%) and in 21 patients microscopically (45%). At 5-year follow
      up the prevalence for macroscopic and microscopic damage was 55% and 60%,
      respectively. The prevalence of mucosal damage was higher in AC patients than in
      SCC patients (1y-FU: 51% [AC] vs. 28% [SCC]; 5y-FU: 68% [AC] vs. 35% [SCC], P <
      0.05). Newly acquired Barrett's esophagus was seen in 10 patients (20%) with two
      of those patients (20%) showing histopathologic proof of neoplasia. This study
      shows a high prevalence of reflux-associated mucosal damage in the remnant
      esophagus one year out of surgery and only a moderate increase in prevalence in
      the following years. Mucosal damage was more frequently seen in AC patients and
      the occurrence of de-novo Barrett's esophagus and de-novo neoplasia was high.
      Endoscopic surveillance with targeted biopsies seems to be an indispensable tool
      to follow patients after esophagectomy appropriately.

PMID- 29036609
TI  - Computed flow and fluorescence over the ocular surface.
AB  - Fluorescein is perhaps the most commonly used substance to visualize tear film
      thickness and dynamics; better understanding of this process aids understanding
      of dry eye syndrome which afflicts millions of people. We study a mathematical
      model for tear film flow, evaporation, solutal transport and fluorescence over
      the exposed ocular surface during the interblink. Transport of the fluorescein
      ion by fluid flow in the tear film affects the intensity of fluorescence via
      changes in concentration and tear film thickness. Evaporation causes increased
      osmolarity and potential irritation over the ocular surface; it also alters
      fluorescein concentration and thus fluorescence. Using thinning rates from in
      vivo measurements together with thin film equations for flow and transport of
      multiple solutes, we compute dynamic results for tear film quantities of
      interest. We compare our computed fluorescent intensity distributions with in
      vivo observations. A number of experimental features are recovered by the model.

PMID- 29036610
TI  - Saddle nose deformity and granulomatosis with polyangiitis.

PMID- 29036608
TI  - Insights into RNA polymerase catalysis and adaptive evolution gained from
      mutational analysis of a locus conferring rifampicin resistance.
AB  - S531 of Escherichia coli RNA polymerase (RNAP) beta subunit is a part of RNA
      binding domain in transcription complex. While highly conserved, S531 is not
      involved in interactions within the transcription complex as suggested by X-ray
      analysis. To understand the basis for S531 conservation we performed systematic
      mutagenesis of this residue. We find that the most of the mutations significantly
      decreased initiation-to-elongation transition by RNAP. Surprisingly, some changes
      enhanced the production of full-size transcripts by suppressing abortive loss of
      short RNAs. S531-R increased transcript retention by establishing a salt bridge
      with RNA, thereby explaining the R substitution at the equivalent position in
      extremophilic organisms, in which short RNAs retention is likely to be an issue.
      Generally, the substitutions had the same effect on bacterial doubling time when
      measured at 20 degrees . Raising growth temperature to 37 degrees  ablated the
      positive influence of some mutations on the growth rate in contrast to their in
      vitro action, reflecting secondary effects of cellular environment on
      transcription and complex involvement of 531 locus in the cell biology. The
      properties of generated RNAP variants revealed an RNA/protein interaction network
      that is crucial for transcription, thereby explaining the details of initiation
      to-elongation transition on atomic level.

PMID- 29036612
TI  - CD40L controls obesity-associated vascular inflammation, oxidative stress, and
      endothelial dysfunction in high fat diet-treated and db/db mice.
AB  - Aims: CD40 ligand (CD40L) signaling controls vascular oxidative stress and
      related dysfunction in angiotensin-II-induced arterial hypertension by regulating
      vascular immune cell recruitment and platelet activation. Here we investigated
      the role of CD40L in experimental hyperlipidemia. Methods and results: Male wild
      type and CD40L-/- mice (C57BL/6 background) were subjected to high fat diet for
      sixteen weeks. Weight, cholesterol, HDL, and LDL levels, endothelial function
      (isometric tension recording), oxidative stress (NADPH oxidase expression,
      dihydroethidium fluorescence) and inflammatory parameters (inducible nitric oxide
      synthase, interleukin-6 expression) were assessed. CD40L expression, weight,
      leptin and lipids were increased, and endothelial dysfunction, oxidative stress
      and inflammation were more pronounced in wild type mice on a high fat diet, all
      of which was almost normalized by CD40L deficiency. Similar results were obtained
      in diabetic db/db mice with CD40/TRAF6 inhibitor (6877002) therapy. In a small
      human study higher serum sCD40L levels and an inflammatory phenotype were
      detected in the blood and Aorta ascendens of obese patients (body mass index >
      35) that underwent by-pass surgery. Conclusion: CD40L controls obesity-associated
      vascular inflammation, oxidative stress and endothelial dysfunction in mice and
      potentially humans. Thus, CD40L represents a therapeutic target in lipid
      metabolic disorders which is a leading cause in cardiovascular disease.

PMID- 29036614
TI  - Identification of a Candidate Mutation in the COL1A2 Gene of a Chow Chow With
      Osteogenesis Imperfecta.
AB  - Osteogenesis imperfecta (OI) is a genetic disease that occurs in humans and
      animals. Individuals with OI exhibit signs of extreme bone fragility and
      osteopenia with frequent fractures and perinatal lethality in severe cases. In
      this study, we report the clinical diagnosis of OI in a dog and the use of
      targeted next-generation sequencing to identify a candidate autosomal dominant
      mutation in the COL1A2 gene. A 5-month-old male Chow Chow was examined with a
      fractured left humerus and resolving, bilateral femoral fractures. Radiographs
      revealed generalized osteopenia and bilateral humeral, radial, and femoral
      fractures. Targeted next-generation sequencing of genes associated with OI in
      humans (COL1A1, COL1A2, LEPRE1, SERPINH1, and CRTAP) revealed a G>A heterozygous
      mutation in the splice donor site of exon 18 of the COL1A2 gene (c.936 + 1G>A).
      The splice donor mutation was not detected among 91 control dogs representing 21
      breeds. A comparative analysis of exon 18 and the exon-intron junction further
      showed that the mutated splice donor site is conserved among vertebrates.
      Altogether, these findings reveal a candidate autosomal splice donor site
      mutation causing OI in an individual Chow Chow.

PMID- 29036613
TI  - Surgical outcomes of robot-assisted rectal cancer surgery using the da Vinci
      Surgical System: a multi-center pilot Phase II study.
AB  - Introduction: We conducted a multi-center pilot Phase II study to examine the
      safety of robotic rectal cancer surgery performed using the da Vinci Surgical
      System during the introduction period of robotic rectal surgery at two institutes
      based on surgical outcomes. Methods: This study was conducted with a prospective,
      multi-center, single-arm, open-label design to assess the safety and feasibility
      of robotic surgery for rectal cancer (da Vinci Surgical System). The primary
      endpoint was the rate of adverse events during and after robotic surgery. The
      secondary endpoint was the completion rate of robotic surgery. Results: Between
      April 2014 and July 2016, 50 patients were enrolled in this study. Of these, 10
      (20%) had rectosigmoid cancer, 17 (34%) had upper rectal cancer, and 23 (46%) had
      lower rectal cancer; six underwent high anterior resection, 32 underwent low
      anterior resection, 11 underwent intersphincteric resection, and one underwent
      abdominoperineal resection. Pathological stages were Stage 0 in 1 patient, Stage
      I in 28 patients, Stage II in 7 patients and Stage III in 14 patients.
      Pathologically complete resection was achieved in all patients. There was no
      intraoperative organ damage or postoperative mortality. Eight (16%) patients
      developed complications of all grades, of which 2 (4%) were Grade 3 or higher,
      including anastomotic leakage (2%) and conversion to open surgery (2%).
      Conclusion: The present study demonstrates the feasibility and safety of robotic
      rectal cancer surgery, as reflected by low morbidity and low conversion rates,
      during the introduction period.

PMID- 29036611
TI  - Progranulin-mediated deficiency of cathepsin D results in FTD and NCL-like
      phenotypes in neurons derived from FTD patients.
AB  - Frontotemporal dementia (FTD) encompasses a group of neurodegenerative disorders
      characterized by cognitive and behavioral impairments. Heterozygous mutations in
      progranulin (PGRN) cause familial FTD and result in decreased PGRN expression,
      while homozygous mutations result in complete loss of PGRN expression and lead to
      the neurodegenerative lysosomal storage disorder neuronal ceroid lipofuscinosis
      (NCL). However, how dose-dependent PGRN mutations contribute to these two
      different diseases is not well understood. Using iPSC-derived human cortical
      neurons from FTD patients harboring PGRN mutations, we demonstrate that PGRN
      mutant neurons exhibit decreased nuclear TDP-43 and increased insoluble TDP-43,
      as well as enlarged electron-dense vesicles, lipofuscin accumulation, fingerprint
      like profiles and granular osmiophilic deposits, suggesting that both FTD and NCL
      like pathology are present in PGRN patient neurons as compared to isogenic
      controls. PGRN mutant neurons also show impaired lysosomal proteolysis and
      decreased activity of the lysosomal enzyme cathepsin D. Furthermore, we find that
      PGRN interacts with cathepsin D, and that PGRN increases the activity of
      cathepsin D but not cathepsins B or L. Finally, we show that granulin E, a
      cleavage product of PGRN, is sufficient to increase cathepsin D activity. This
      functional relationship between PGRN and cathepsin D provides a possible
      explanation for overlapping NCL-like pathology observed in patients with
      mutations in PGRN or CTSD, the gene encoding cathepsin D. Together, our work
      identifies PGRN as an activator of lysosomal cathepsin D activity, and suggests
      that decreased cathepsin D activity due to loss of PGRN contributes to both FTD
      and NCL pathology in a dose-dependent manner.

PMID- 29036615
TI  - Monitoring of cerebral oximetry during head-up tilt test in adults with history
      of syncope and orthostatic intolerance.
AB  - Aims : We applied near-infrared-spectroscopy (NIRS) to measure absolute frontal
      cerebral tissue oxygen saturation (SctO2) during head-up tilt test (HUT) in
      patients investigated for unexplained syncope. Methods and results : Synchronized
      non-invasive beat-to-beat haemodynamic monitoring, ECG, SctO2 (NIRS; normal
      range: 60-80%), and peripheral oxygen saturation (left hand, SpO2) were applied
      during HUT in a random sample of patients with unexplained syncope. Tracings of
      54 patients (mean-age: 55 +/- 19 years, 39% male) with negative HUT, vasovagal
      syncope (VVS), or orthostatic hypotension (OH) were analysed. In 44 patients HUT
      was diagnostic, in 10 HUT was negative. Thirty-one experienced VVS. Of these, 6
      had spontaneous and 25 nitroglycerin-induced syncope. Thirteen patients had
      orthostatic hypotension (OH). Although there was no significant change in mean
      arterial pressure from baseline to 1 min before syncope or end of passive HUT
      phase (-1.4 +/- 13.9 mmHg; P = 0.45), there was a significant fall in SctO2
      during the same period (-3.2 +/- 3.2%; P <= 0.001). Among patients who
      experienced syncope, a decrease in SctO2 from 71 +/- 5% at baseline to 53 +/- 9%
      (P < 0.001) at syncope was observed. During HUT, there was a significant
      difference in delta SctO2 between spontaneous VVS (-4.5 +/- 3.0%) and negative
      HUT (-1.3 +/- 1.9%; P  = 0.021), but not between spontaneous VVS and OH (-5.4 +/-
      4.2%; P = 0.65). In spontaneous VVS, progressive decrease of SctO2 was
      independent of mean arterial pressure decrease (P  = 0.22). Conclusions:
      Progressive decrease in cerebral tissue oxygenation independent of mean-arterial
      pressure may precede spontaneous vasovagal reflex during tilt. Patients
      experience syncope when SctO2 falls below 60%. These data confirm clinical
      utility of absolute cerebral oximetry monitoring for syncope investigation. We
      applied NIRS to measure frontal cerebral tissue oxygen saturation (SctO2) during
      head-up tilt test (HUT) in patients with unexplained syncope. In 44 of 54
      patients, HUT was diagnostic. In patients with syncope, a significant SctO2
      decrease was observed. Different patterns of SctO2 can be detected.

PMID- 29036616
TI  - DeepLoc: prediction of protein subcellular localization using deep learning.
AB  - Motivation: The prediction of eukaryotic protein subcellular localization is a
      well-studied topic in bioinformatics due to its relevance in proteomics research.
      Many machine learning methods have been successfully applied in this task, but in
      most of them, predictions rely on annotation of homologues from knowledge
      databases. For novel proteins where no annotated homologues exist, and for
      predicting the effects of sequence variants, it is desirable to have methods for
      predicting protein properties from sequence information only. Results: Here, we
      present a prediction algorithm using deep neural networks to predict protein
      subcellular localization relying only on sequence information. At its core, the
      prediction model uses a recurrent neural network that processes the entire
      protein sequence and an attention mechanism identifying protein regions important
      for the subcellular localization. The model was trained and tested on a protein
      dataset extracted from one of the latest UniProt releases, in which
      experimentally annotated proteins follow more stringent criteria than previously.
      We demonstrate that our model achieves a good accuracy (78% for 10 categories;
      92% for membrane-bound or soluble), outperforming current state-of-the-art
      algorithms, including those relying on homology information. Availability and
      implementation: The method is available as a web server at
      http://www.cbs.dtu.dk/services/DeepLoc. Example code is available at
      https://github.com/JJAlmagro/subcellular_localization. The dataset is available
      at http://www.cbs.dtu.dk/services/DeepLoc/data.php. Contact: jjalma@dtu.dk.

PMID- 29036618
TI  - Unsuccessful treatment in pulmonary tuberculosis: factors and a consequent
      predictive model.
AB  - Background: Cure is particularly valuable in pulmonary cases (PTB), as
      unsuccessful treatment fuels incidence and resistance to antibiotics. This study
      aims to identify individual factors of PTB unsuccessful treatment in Portugal and
      to develop a consequent predictive model. Methods: Using the Portuguese TB
      surveillance database (SVIG-TB), PTB cases older than 15 years notified from 2000
      to 2012 in Continental Portugal were analyzed. Unsuccessful treatment included
      the WHO categories (failure, default, death and transferred out). Based on a
      literature review, predictors involved sociodemographic, behavioral, disease
      related and treatment-related factors. Binary logistic regression was used to
      estimate unsuccessful treatment factors and to develop the predictive risk model.
      Results: The unsuccessful outcome rate in PTB patients was of 11.9%. The
      predictive model included the following factors: TB/HIV co-infection (OR 4.93),
      age over 64 years (OR 4.37), IV drugs abuse (OR 2.29), other diseases (excluding
      HIV and Diabetes, OR 2.09) and retreatment (OR 1.44), displaying a rather good
      validity. Conclusion: The overall treatment unsuccessful treatment rate in PTB
      patients complies with the 85% WHO success threshold. The predictive model of
      unsuccessful treatment proved well. Nomogram representation allows an early,
      intuitive identification of PTB patients at increased risk. The model is liable
      to widespread use as a prognostic tool.

PMID- 29036617
TI  - Arrayed mutant haploid embryonic stem cell libraries facilitate phenotype-driven
      genetic screens.
AB  - Forward genetic screens using mammalian embryonic stem (ES) cells have identified
      genes required for numerous cellular processes. However, loss-of-function screens
      are more difficult to conduct in diploid cells because, in most cases, both
      alleles of a gene must be mutated to exhibit a phenotype. Recently, mammalian
      haploid ES cell lines were successfully established and applied to several
      recessive genetic screens. However, all these screens were performed in mixed
      pools of mutant cells and were mainly based on positive selection. In general,
      negative screening is not easy to apply to these mixed pools, although
      quantitative deep sequencing of mutagen insertions can help to identify some
      'missing' mutants. Moreover, the interplay between different mutant cells in the
      mixed pools would interfere with the readout of the screens. Here, we developed a
      method for rapidly generating arrayed haploid mutant libraries in which the
      proportion of homozygous mutant clones can reach 85%. After screening thousands
      of individual mutant clones, we identified a number of novel factors required for
      the onset of differentiation in ES cells. A negative screen was also conducted to
      discover mutations conferring cells with increased sensitivity to DNA double
      strand breaks induced by the drug doxorubicin. Both of these screens illustrate
      the value of this system.

PMID- 29036620
TI  - FE Controls the Transcription of Downstream Flowering Regulators Through Two
      Distinct Mechanisms in Leaf Phloem Companion Cells.
AB  - In the facultative long-day plant Arabidopsis thaliana, FLOWERING LOCUS T (FT),
      encoding the mobile hormone florigen, plays an essential role in modulating the
      optimal timing of flowering to ensure reproductive success. Under inductive long
      day conditions, the transcription of FT is activated by the CONSTANS (CO)/NUCLEAR
      FACTOR-Y (NF-Y) protein complex in leaf phloem companion cells. FT is transported
      to the shoot apical meristem through interaction with florigen transporters, such
      as SODIUM POTASSIUM ROOT DEFECTIVE 1 (NaKR1). Some regulators involved in
      photoperiod-dependent FT function have been reported previously; however, the
      molecular mechanism that coordinates FT protein synthesis and transport
      efficiently needs to be investigated. The present study examined the role of an
      Myb-related transcription factor, FE, in the activation of FT gene transcription
      and FT protein transport. Expression analysis using FE-inducible systems and
      chromatin immunoprecipitation assays showed that FE directly bound to the FT and
      NaKR1 promoters and activated the transcription of downstream target genes. FE
      failed to activate FT expression without CO function, whereas FE-mediated NaKR1
      induction was not affected by CO function. Taken together, our data indicate that
      FE regulates the transcription of FT and florigen transporter genes via different
      mechanisms.

PMID- 29036619
TI  - The effects of DNA supercoiling on G-quadruplex formation.
AB  - Guanine-rich DNAs can fold into four-stranded structures that contain stacks of G
      quartets. Bioinformatics studies have revealed that G-rich sequences with the
      potential to adopt these structures are unevenly distributed throughout genomes,
      and are especially found in gene promoter regions. With the exception of the
      single-stranded telomeric DNA, all genomic G-rich sequences will always be
      present along with their C-rich complements, and quadruplex formation will be in
      competition with the corresponding Watson-Crick duplex. Quadruplex formation must
      therefore first require local dissociation (melting) of the duplex strands. Since
      negative supercoiling is known to facilitate the formation of alternative DNA
      structures, we have investigated G-quadruplex formation within negatively
      supercoiled DNA plasmids. Plasmids containing multiple copies of (G3T)n and
      (G3T4)n repeats, were probed with dimethylsulphate, potassium permanganate and S1
      nuclease. While dimethylsulphate footprinting revealed some evidence for G
      quadruplex formation in (G3T)n sequences, this was not affected by supercoiling,
      and permanganate failed to detect exposed thymines in the loop regions. (G3T4)n
      sequences were not protected from DMS and showed no reaction with permanganate.
      Similarly, both S1 nuclease and 2D gel electrophoresis of DNA topoisomers did not
      detect any supercoil-dependent structural transitions. These results suggest that
      negative supercoiling alone is not sufficient to drive G-quadruplex formation.

PMID- 29036621
TI  - Comparisons of the clinical outcomes of different postoperative radiation
      strategies for treatment of head and neck squamous cell carcinoma.
AB  - Purpose: We previously reported unfavorable locoregional control with limited
      field postoperative radiotherapy for head and neck squamous cell carcinoma
      patients and thus revised the strategy to cover the whole neck. Head and neck
      squamous cell carcinoma Patients' outcomes were retrospectively analyzed to
      compare the efficacy of two treatments. Material and methods: Before 2010, the
      clinical target volume covered the tumor bed and/or involved the neck region.
      Since 2011, whole-neck irradiation was planned. Univariate analysis, multivariate
      analysis, and propensity score matching were performed. The study included 275
      patients: 186 received limited field postoperative radiotherapy and 89 received
      whole-neck postoperative radiotherapy. The median follow-up time for the entire
      cohort was 40.8 months. Results: In univariate analysis, the radiation strategy
      had no significant effect on overall survival and progression-free survival. In
      multivariate analysis, whole-neck postoperative radiotherapy was a favorable
      factor for overall survival, progression-free survival, and locoregional control.
      Propensity score matching resulted in a cohort comprising 118 well-matched
      patients evenly divided between the limited field postoperative radiotherapy and
      whole-neck postoperative radiotherapy groups. Whole-neck postoperative
      radiotherapy group achieved a significantly better 2-year overall survival (56.4%
      vs. 78.1%; P = 0.003), 2-year progression-free survival (34.7% vs. 59.8%; P =
      0.009), and 2-year locoregional control (54.4% vs. 83.2%; P < 0.001). The limited
      field postoperative radiotherapy group developed significantly more locoregional
      recurrences both in-field (35.2% vs. 15.1%, P = 0.003) and out-of-field (25.0%
      vs. 0%, P < 0.001) in the matched-pair cohort. Conclusion: Whole-neck
      postoperative radiotherapy is a more appropriate choice than limited field
      postoperative radiotherapy to improve overall survival, progression-free survival
      and locoregional control.

PMID- 29036622
TI  - COMPARISON BETWEEN PADC AND FNTD NEUTRON DETECTOR SYSTEMS IN BLIND TESTS.
AB  - The objective of this study was to compare a neutron dosimetry system based on
      polyallyl diglycol carbonate (PADC) detectors with a new system based on
      Al2O3:C,Mg fluorescence nuclear track detectors (FNTD). The irradiations,
      performed as part of an intercomparison organized by the Physikalisch-Technische
      Bundesanstalt (PTB), Germany, were on a PMMA phantom with 252Cf or 241Am-Be
      source, usually with the phantom surface perpendicular to the radiation beam (0
      degrees  angle), and with Hp(10) values between 0.3 and 7 mSv. One 252Cf
      irradiation was performed at 30 degrees  angle, and one with an additional 1 mSv
      gamma irradiation. The results showed an agreement between the two techniques
      with an average and maximum difference between PADCs and FNTDs of 1.5 and 22%,
      respectively, if one compares only cases of doses >1 mSv. For one of the
      irradiation conditions with dose of 0.9 mSv, use of the incorrect calibration
      factor for the FNTD (252Cf instead of 241Am-Be) led to reported values ~*2 larger
      than the given doses, due to low statistics in the determination of the ratio
      between 6Li-doped glass and polyethylene neutron converters. Although the FNTD
      track analysis algorithm may need further development, the results presented here
      demonstrate the feasibility of the FNTD technology and indicate areas requiring
      improvements.

PMID- 29036623
TI  - Predictors of mortality in high-risk patients with QT prolongation in a community
      hospital.
AB  - Aims: To determine predictors of mortality in patients with corrected QT interval
      (QTc) >= 500 ms in a community hospital. Methods and results: In this
      retrospective observational study, we searched the electrocardiogram (ECG)
      database at Telemark Hospital Trust, Norway, from January 2004 to December 2014.
      Medication, electrolyte abnormalities, and medical conditions known to prolong
      the QT interval were recorded. From the medical records, we assessed whether the
      prolonged QTc was noted by the health care providers. We identified 1531 patients
      (age = 70 +/- 15 years, 59% female) with an ECG with QTc >= 500 ms. All-cause
      mortality during 952 (range 0-4161) days of follow-up was 50% (n =  765/1531).
      Main predictors of mortality were aborted cardiac arrest [hazard ratio (HR) 2.40,
      95% confidence interval (CI) 1.44-4.01; P = 0.001], cerebral stroke/head trauma
      (HR 2.28, 95% CI 1.70-3.05; P < 0.001), and heart failure (HR 1.74, 95% CI 1.43
      2.12; P< 0.001). Females with prolonged QTc had better survival compared with
      males (P = 0.006). We constructed a risk-weighted QTc mortality score. QT
      prolongation was acknowledged in the medical records in 12% of the cases.
      Conclusions: QTc >= 500 ms was associated with high all-cause mortality with
      increased mortality in males compared with females. A new QTc mortality score was
      constructed to predict mortality. Only a minority of cases with prolonged QTc >=
      500 ms were acknowledged in the medical records.

PMID- 29036625
TI  - OsPht1;8, a phosphate transporter, is involved in auxin and phosphate starvation
      response in rice.
AB  - The responses of plants to auxin and phosphate (Pi) starvation are closely
      linked. However, the underlying mechanisms connecting the Pi starvation (-Pi)
      responses to auxin are largely unclear. Here, we show that OsPht1;8 (OsPT8), a
      phosphate transporter, functions in both the auxin and -Pi responses in rice
      (Oryza sativa L.) and tobacco (Nicotiana tabacum). The overexpression of OsPT8
      (OsPT8-Oe) led to the loss of sensitivity to auxin and -Pi in adventitious roots,
      lateral roots, and root hairs in rice. The expression levels of OsPT8 and
      pOsPT8::GUS staining in roots, root-shoot junctions and leaves of rice were
      induced by IAA treatments. The number of young lateral roots in the OsPT8-Oe
      transgenic rice, which had higher auxin concentrations, was distinctly more than
      that in the wild-type, possibly as a result of increased expression of auxin
      related genes under normal Pi condition. Moreover, tobacco overexpressing OsPT8
      had a similar root phenotype to OsPT8-Oe rice. These data reveal a novel
      biological function of OsPT8 in the cross-talk between Pi and auxin signaling,
      and provide new evidence for the linkage between auxin and -Pi responses.

PMID- 29036624
TI  - Genomic Signatures of Sexual Conflict.
AB  - Sexual conflict is a specific class of intergenomic conflict that describes the
      reciprocal sex-specific fitness costs generated by antagonistic reproductive
      interactions. The potential for sexual conflict is an inherent property of having
      a shared genome between the sexes and, therefore, is an extreme form of an
      environment-dependent fitness effect. In this way, many of the predictions from
      environment-dependent selection can be used to formulate expected patterns of
      genome evolution under sexual conflict. However, the pleiotropic and transmission
      constraints inherent to having alleles move across sex-specific backgrounds from
      generation to generation further modulate the anticipated signatures of
      selection. We outline methods for detecting candidate sexual conflict loci both
      across and within populations. Additionally, we consider the ability of genome
      scans to identify sexually antagonistic loci by modeling allele frequency changes
      within males and females due to a single generation of selection. In particular,
      we highlight the need to integrate genotype, phenotype, and functional
      information to truly distinguish sexual conflict from other forms of sexual
      differentiation.

PMID- 29036628
TI  - Social marketing targeting Indigenous peoples: a systematic review.

PMID- 29036627
TI  - Using uncertainty to link and rank evidence from biomedical literature for model
      curation.
AB  - Motivation: In recent years, there has been great progress in the field of
      automated curation of biomedical networks and models, aided by text mining
      methods that provide evidence from literature. Such methods must not only extract
      snippets of text that relate to model interactions, but also be able to
      contextualize the evidence and provide additional confidence scores for the
      interaction in question. Although various approaches calculating confidence
      scores have focused primarily on the quality of the extracted information, there
      has been little work on exploring the textual uncertainty conveyed by the author.
      Despite textual uncertainty being acknowledged in biomedical text mining as an
      attribute of text mined interactions (events), it is significantly understudied
      as a means of providing a confidence measure for interactions in pathways or
      other biomedical models. In this work, we focus on improving identification of
      textual uncertainty for events and explore how it can be used as an additional
      measure of confidence for biomedical models. Results: We present a novel method
      for extracting uncertainty from the literature using a hybrid approach that
      combines rule induction and machine learning. Variations of this hybrid approach
      are then discussed, alongside their advantages and disadvantages. We use
      subjective logic theory to combine multiple uncertainty values extracted from
      different sources for the same interaction. Our approach achieves F-scores of
      0.76 and 0.88 based on the BioNLP-ST and Genia-MK corpora, respectively, making
      considerable improvements over previously published work. Moreover, we evaluate
      our proposed system on pathways related to two different areas, namely leukemia
      and melanoma cancer research. Availability and implementation: The leukemia
      pathway model used is available in Pathway Studio while the Ras model is
      available via PathwayCommons. Online demonstration of the uncertainty extraction
      system is available for research purposes at http://argo.nactem.ac.uk/test. The
      related code is available on https://github.com/c-zrv/uncertainty_components.git.
      Details on the above are available in the Supplementary Material. Contact:
      sophia.ananiadou@manchester.ac.uk. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 29036626
TI  - Detection of an Underlying 22q11.2 Duplication in a Female Neonate With Trisomy
      18.
AB  - Current guidelines indicate that in patients with developmental disabilities or
      congenital anomalies, chromosomal microarray (CMA) is a first-tier diagnostic
      test. However, for patients with obvious chromosomal syndromes such as trisomy
      13, 18, and 21, G-banded karyotyping is still recommended over CMA for
      establishing a diagnosis. In the case presented herein, a female neonate was
      suspected of having trisomy 18 based on pre- and postnatal evaluations.
      Karyotyping was requested but not performed due to insufficient cell growth;
      Interphase fluorescence in situ hybridization (i-FISH) found an extra copy of
      chromosome 18. CMA analysis uncovered gain of chromosome 18 and an additional
      duplication in chromosome 22q11.2, which went undetected with FISH. Our patient
      died within 40 hours after birth, but it is expected that patients with
      recognizable chromosomal syndromes could benefit from the discovery of coexisting
      copy number variations (CNVs) using CMA. This case shows that CMA can be a useful
      test for patients with recognizable chromosomal syndromes because of the
      potential benefits for patients and their families when co-existing CNVs are
      found.

PMID- 29036629
TI  - Nanotechnology: A Promising New Paradigm for the Control of Pain.
AB  - Objective: The objective of this article is to critically review both preclinical
      and clinical studies that focus on the use of nanotechnology for both acute and
      chronic pain management, surveying both diagnostic and therapeutic applications.
      The article also provides information on nanotechnology for pain practitioners,
      so that they may better understand how this technology works and how it may be
      applied to their day-to-day clinical practice. Study Design: Narrative review.
      Methods: The Pubmed NCBI and EMBASE databases were utilized to review published
      reports of in vivo and clinical studies that focus on using nanotechnology for
      pain management applications in both the acute and chronic pain settings.
      Results: Articles were screened by title, abstract, and full article review. They
      were then analyzed by specific clinical indications, and appropriate data were
      presented based on a critical analysis of those articles. Conclusions: As the
      development of nanomedical applications in acute and chronic pain management
      continues, medical practitioners should consider their growing potential to
      enhance the care of patients who are consistently living with pain. Current
      barriers to implementation include manufacturing scale-up for commercial
      viability, long-term nanoparticle toxicity considerations, and high cost for
      successful passage through clinical trials. These challenges will need to be
      overcome with ongoing translational research efforts in collaboration with
      industry and government bodies such as the Food and Drug Administration (FDA).

PMID- 29036631
TI  - ID(H)entifying checkpoint inhibitor candidates among diffuse glioma.

PMID- 29036630
TI  - Resequencing Epithelial Sodium Channel Genes Identifies Rare Variants Associated
      With Blood Pressure Salt-Sensitivity: The GenSalt Study.
AB  - BACKGROUND: A resequencing study of renal epithelial sodium channel (ENaC) genes
      was conducted to identify rare variants associated with blood pressure (BP) salt
      sensitivity. METHODS: The Genetic Epidemiology Network of Salt-Sensitivity
      (GenSalt) study was conducted among 1,906 participants who underwent a 7-day low
      sodium followed by a 7-day high-sodium feeding-study. The 300 most salt-sensitive
      and 300 most salt-resistant GenSalt participants were selected for the
      resequencing study. Three ENaC genes (SCNN1A, SCNN1B, and SCNN1G) were
      resequenced using capillary-based sequencing methods. Traditional burden tests
      were utilized to examine association between rare variants and BP salt
      sensitivity. Associations of low-frequency and common variants were tested using
      single-marker analyses. RESULTS: Carriers of SCNN1A rare variants had a 0.52 [95%
      confidence interval (CI): 0.32-0.85] decreased odds of BP salt-sensitivity
      compared with noncarriers. Neither SCNN1B nor SCNN1G associated with salt
      sensitivity of BP in rare variant analyses (P = 0.65 and 0.48, respectively). In
      single-marker analyses, 3 independent common variants in SCNN1A, rs11614164,
      rs4764586, and rs3741914, associated with salt-sensitivity after Bonferroni
      correction (P = 4.4 * 10-4, 1.1 * 10-8, and 1.3 * 10-3). Each copy of the minor
      allele of rs4764586 was associated with a 1.36-fold (95% CI: 1.23-1.52) increased
      odds of salt-sensitivity, whereas each copy of the minor allele of rs11614164 and
      rs3741914 was associated with 0.68-fold (95% CI: 0.55-0.84) and 0.69-fold (95%
      CI: 0.54-0.86) decreased odds of salt-sensitivity, respectively. CONCLUSIONS:
      This study demonstrated for the first time a relationship between rare variants
      in the ENaC pathway and BP salt-sensitivity. Future replication and functional
      studies are needed to confirm the findings in this study. CLINICAL TRIAL
      REGISTRY: Trial Number NCT00721721.

PMID- 29036634
TI  - ULTRAFINE AEROSOL INFLUENCE ON THE SAMPLING BY CASCADE IMPACTOR.
AB  - Cascade impactors based on inertial deposition of aerosols are widely used to
      determine the size distribution of radioactive aerosols. However, there are
      situations where radioactive aerosols are represented by particles with a
      diameter of 1-5 nm. In this case, ultrafine aerosols can be deposited on impactor
      cascades by diffusion mechanism. The influence of ultrafine aerosols (1-5 nm) on
      the response of three different types of cascade impactors was studied. It was
      shown that the diffusion deposition of ultrafine aerosols can distort the
      response of the cascade impactor. The influence of diffusion deposition of
      ultrafine aerosols can be considerably removed by the use of mesh screens or
      diffusion battery installed before cascade impactor during the aerosol sampling.

PMID- 29036633
TI  - RNA sequencing of Brassica napus reveals cellular redox control of Sclerotinia
      infection.
AB  - Brassica napus is one of the world's most valuable oilseeds and is under constant
      pressure by the necrotrophic fungal pathogen, Sclerotinia sclerotiorum, the
      causal agent of white stem rot. Despite our growing understanding of host
      pathogen interactions at the molecular level, we have yet to fully understand the
      biological processes and underlying gene regulatory networks responsible for
      determining disease outcomes. Using global RNA sequencing, we profiled gene
      activity at the first point of infection on the leaf surface 24 hours after
      pathogen exposure in susceptible (B. napus cv. Westar) and tolerant (B. napus cv.
      Zhongyou 821) plants. We identified a family of ethylene response factors that
      may contribute to host tolerance to S. sclerotiorum by activating genes
      associated with fungal recognition, subcellular organization, and redox
      homeostasis. Physiological investigation of redox homeostasis was further studied
      by quantifying cellular levels of the glutathione and ascorbate redox pathway and
      the cycling enzymes associated with host tolerance to S. sclerotiorum. Functional
      characterization of an Arabidopsis redox mutant challenged with the fungus
      provides compelling evidence into the role of the ascorbate-glutathione redox hub
      in the maintenance and enhancement of plant tolerance against fungal pathogens.

PMID- 29036632
TI  - Mapping Compulsivity in the DSM-5 Obsessive Compulsive and Related Disorders:
      Cognitive Domains, Neural Circuitry, and Treatment.
AB  - Compulsions are repetitive, stereotyped thoughts and behaviors designed to reduce
      harm. Growing evidence suggests that the neurocognitive mechanisms mediating
      behavioral inhibition (motor inhibition, cognitive inflexibility) reversal
      learning and habit formation (shift from goal-directed to habitual responding)
      contribute toward compulsive activity in a broad range of disorders. In obsessive
      compulsive disorder, distributed network perturbation appears focused around the
      prefrontal cortex, caudate, putamen, and associated neuro-circuitry. Obsessive
      compulsive disorder-related attentional set-shifting deficits correlated with
      reduced resting state functional connectivity between the dorsal caudate and the
      ventrolateral prefrontal cortex on neuroimaging. In contrast, experimental
      provocation of obsessive compulsive disorder symptoms reduced neural activation
      in brain regions implicated in goal-directed behavioral control (ventromedial
      prefrontal cortex, caudate) with concordant increased activation in regions
      implicated in habit learning (presupplementary motor area, putamen). The
      ventromedial prefrontal cortex plays a multifaceted role, integrating affective
      evaluative processes, flexible behavior, and fear learning. Findings from a
      neuroimaging study of Pavlovian fear reversal, in which obsessive compulsive
      disorder patients failed to flexibly update fear responses despite normal initial
      fear conditioning, suggest there is an absence of ventromedial prefrontal cortex
      safety signaling in obsessive compulsive disorder, which potentially undermines
      explicit contingency knowledge and may help to explain the link between cognitive
      inflexibility, fear, and anxiety processing in compulsive disorders such as
      obsessive compulsive disorder.

PMID- 29036635
TI  - Barbara Fish and a Short History of the Neurodevelopmental Hypothesis of
      Schizophrenia.
AB  - The neurodevelopmental hypothesis of schizophrenia has become a paradigm broadly
      accepted in today's research in schizophrenia and its spectrum. This article
      traces the historical development of the neurodevelopmental hypothesis of
      schizophrenia up until the time of its explicit formulation in 1987, by
      Weinberger and by Murray and Lewis, with a main focus on the seminal contribution
      of Barbara Fish to its conception and elaboration.

PMID- 29036637
TI  - Examining the contribution of cell wall polysaccharides to the mechanical
      properties of apple parenchyma tissue using exogenous enzymes.
AB  - The viscoelastic mechanical properties of water-rich plant tissues are
      fundamental for many aspects of organ physiology and plant functioning. These
      properties are determined partly by the water in cellular vacuole and partly by
      the mechanical properties of the cell wall, the latter varying according to the
      composition and organization of its polysaccharides. In this study, relationships
      between the viscoelastic properties of apple cortex parenchyma tissue and cell
      wall pectin, hemicelluloses, and cellulose structures were studied by infusing
      the tissue with selected sets of purified enzymes in a controlled osmoticum. The
      results showed that tissue elasticity and viscosity were related, and controlled
      to variable extents by all the targeted polysaccharides. Among them, pectic
      homogalacturonan domains, crystalline cellulose, and fucosylated xyloglucan were
      revealed as being of prime importance in determining the viscoelastic mechanical
      properties of apple cortex tissue.

PMID- 29036639
TI  - Avoiding phantasms.

PMID- 29036636
TI  - Genetic reduction of Nrf2 exacerbates cognitive deficits in a mouse model of
      Alzheimer's disease.
AB  - Aging is the major risk factor for several neurodegenerative diseases, including
      Alzheimer's disease (AD). However, the mechanisms by which aging contributes to
      neurodegeneration remain elusive. The nuclear factor (erythroid-derived 2)-like 2
      (Nrf2) is a transcription factor that regulates expression of a vast number of
      genes by binding to the antioxidant response element. Nrf2 levels decrease as a
      function of age, and reduced Nrf2 levels have been reported in postmortem human
      brains and animal models of AD. Nevertheless, it is still unknown whether Nrf2
      plays a role in the cognitive deficits associated with AD. To address this
      question, we used a genetic approach to remove the Nrf2 gene from APP/PS1 mice, a
      widely used animal model of AD. We found that the lack of Nrf2 significantly
      exacerbates cognitive deficits in APP/PS1, without altering gross motor function.
      Specifically, we found an exacerbation of deficits in spatial learning and
      memory, as well as in working and associative memory. Different brain regions
      control these behavioral tests, indicating that the lack of Nrf2 has a global
      effect on brain function. The changes in cognition were linked to an increase in
      Abeta and interferon-gamma (IFNgamma) levels, and microgliosis. The changes in
      IFNgamma levels are noteworthy as previously published evidence indicates that
      IFNgamma can increase microglia activation and induce Abeta production. Our data
      suggest a clear link between Nrf2 and AD-mediated cognitive decline and further
      strengthen the connection between Nrf2 and AD.

PMID- 29036641
TI  - Inverted V sign: subacute combined degeneration of the spinal cord.

PMID- 29036640
TI  - Toxicokinetics of the Synthetic Cathinone alpha-Pyrrolidinohexanophenone.
AB  - Synthetic cathinones inhibit monoamine transporters, such as serotonin,
      norepinephrine, and dopamine transporters, and act on the central nervous system
      via increasing synaptic concentrations of monoamines. These compounds, which are
      highly addictive and potentially poisonous, are new psychoactive substances. In
      this study, we investigated the toxicokinetics of the synthetic cathinone, alpha
      pyrrolidinohexanophenone (alpha-PHP), and assessed the relationship between the
      toxicokinetics and the long-term clinical symptoms induced by alpha-PHP in a male
      patient. The patient (39 years old) suddenly started uttering inarticulate words
      and demonstrating incomprehensible behavior in his house, and was brought to the
      emergency department of Iwate Medical University hospital. He presented with
      psychotic symptoms, such as hallucinations and delusion; however, his vital signs
      were normal. The hallucinations and delusion improved by the third day of
      hospitalization. Toxicological analysis was performed using liquid chromatography
      tandem mass spectrometry with QuEChERS extraction. alpha-PHP was detected in his
      serum at a concentration of 175 ng/mL on his arrival at the hospital. His serum
      concentrations of alpha-PHP were serially determined and their natural logarithms
      were plotted against time after arrival. Although serum concentrations at early
      time points were lacking, the obtained curve was consistent with a two
      compartment model and indicated a serum elimination half-life of 37 h. The long
      lasting psychotic symptoms induced by synthetic cathinones appear to be
      correlated with their toxicokinetic characteristics, such as their long half
      lives. Finally, interpreting the toxicokinetics of synthetic cathinones may
      provide useful information for the toxicological assessment of new psychoactive
      substances for forensic and clinical purposes.

PMID- 29036638
TI  - The basic tilted helix bundle domain of the prolyl isomerase FKBP25 is a novel
      double-stranded RNA binding module.
AB  - Prolyl isomerases are defined by a catalytic domain that facilitates the cis
      trans interconversion of proline residues. In most cases, additional domains in
      these enzymes add important biological function, including recruitment to a set
      of protein substrates. Here, we report that the N-terminal basic tilted helix
      bundle (BTHB) domain of the human prolyl isomerase FKBP25 confers specific
      binding to double-stranded RNA (dsRNA). This binding is selective over DNA as
      well as single-stranded oligonucleotides. We find that FKBP25 RNA-association is
      required for its nucleolar localization and for the vast majority of its protein
      interactions, including those with 60S pre-ribosome and early ribosome biogenesis
      factors. An independent mobility of the BTHB and FKBP catalytic domains supports
      a model by which the N-terminus of FKBP25 is anchored to regions of dsRNA,
      whereas the FKBP domain is free to interact with neighboring proteins. Apart from
      the identification of the BTHB as a new dsRNA-binding module, this domain adds to
      the growing list of auxiliary functions used by prolyl isomerases to define their
      primary cellular targets.

PMID- 29036643
TI  - GLASS: assisted and standardized assessment of gene variations from Sanger
      sequence trace data.
AB  - Motivation: Sanger sequencing is still being employed for sequence variant
      detection by many laboratories, especially in a clinical setting. However,
      chromatogram interpretation often requires manual inspection and in some cases,
      considerable expertise. Results: We present GLASS, a web-based Sanger sequence
      trace viewer, editor, aligner and variant caller, built to assist with the
      assessment of variations in 'curated' or user-provided genes. Critically, it
      produces a standardized variant output as recommended by the Human Genome
      Variation Society. Availability and implementation: GLASS is freely available at
      http://bat.infspire.org/genomepd/glass/ with source code at
      https://github.com/infspiredBAT/GLASS. Contact: nikos.darzentas@gmail.com or
      malcikova.jitka@fnbrno.cz. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29036642
TI  - Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in
      mouse embryonic stem cells.
AB  - Transposable elements (TEs) compose about 40% of the murine genome.
      Retrotransposition of active TEs such as LINE-1 (L1) tremendously impacts genetic
      diversification and genome stability. Therefore, transcription and transposition
      activities of retrotransposons are tightly controlled. Here, we show that the
      Kruppel-like zinc finger protein Zfp281 directly binds and suppresses a subset of
      retrotransposons, including the active young L1 repeat elements, in mouse
      embryonic stem (ES) cells. In addition, we find that Zfp281-regulated L1s are
      highly enriched for 5-hydroxymethylcytosine (5hmC) and H3K4me3. The COMPASS-like
      H3K4 methyltransferase Mll2 is the major H3K4me3 methylase at the Zfp281
      regulated L1s and required for their proper expression. Our studies also reveal
      that Zfp281 functions partially through recruiting the L1 regulators DNA
      hydroxymethylase Tet1 and Sin3A, and restricting Mll2 at these active L1s,
      leading to their balanced expression. In summary, our data indicate an
      instrumental role of Zfp281 in suppressing the young active L1s in mouse ES
      cells.

PMID- 29036645
TI  - Genomic and Transcriptomic Compilation of Chloroplast Ionic Transporters of
      Physcomitrella patens. Study of NHAD Transporters in Na+ and K+ Homeostasis.
AB  - K+ is widely used by plant cells, whereas Na+ can easily reach toxic levels
      during plant growth, which typically occurs in saline environments; however, the
      effects and functions in the chloroplast have been only roughly estimated.
      Traditionally, the occurrence of ionic fluxes across the chloroplast envelope or
      the thylakoid membranes has been mostly deduced from physiological measurements
      or from knowledge of chloroplast metabolism. However, many of the proteins
      involved in these fluxes have not yet been characterized. Based on genomic and
      RNA sequencing (RNA-seq) analyses, we present a comprehensive compilation of
      genes encoding putative ion transporters and channels expressed in the
      chloroplasts of the moss Physcomitrella patens, with a special emphasis on those
      related to Na+ and K+ fluxes. Based on the functional characterization of nhad
      mutants, we also discuss the putative role of NHAD transporters in Na+
      homeostasis and osmoregulation of this organelle and the putative contribution of
      chloroplasts to salt tolerance in this moss. We demonstrate that NaCl does not
      affect the chloroplast functionality in Physcomitrella despite significantly
      modifying expression of ionic transporters and cellular morphology, specifically
      the chloroplast ultrastructure, revealing a high starch accumulation.
      Additionally, NHAD transporters apparently do not play any essential roles in
      salt tolerance.

PMID- 29036647
TI  - INVESTIGATION OF SECONDARY MIXED RADIATION FIELD AROUND A MEDICAL LINEAR
      ACCELERATOR.
AB  - The aim of this study is to investigate secondary mixed radiation field around
      linac, as the first part of an overall assessment of out-of-field contribution of
      neutron dose for new advanced radiation dose delivery techniques. All
      measurements were performed around Varian Clinic 2300 C/D accelerator at Maria
      Sklodowska-Curie Memorial, Cancer Center and Institute of Oncology, Krakow
      Branch. Recombination chambers REM-2 and GW2 were used for recombination index of
      radiation quality Q4 determination (as an estimate of quality factor Q),
      measurement of total tissue dose Dt and calculation of gamma and neutron
      components to Dt. Estimation of Dt and Q4 allowed for the ambient dose equivalent
      H*(10) per monitor unit (MU) calculations. Measurements around linac were
      performed on the height of the middle of the linac's head (three positions) and
      on the height of the linac's isocentre (five positions). Estimation of secondary
      radiation level was carried out for seven different configurations of upper and
      lower jaws position and multileaf collimator set open or closed in each position.
      Study includes the use of two photon beam modes: 6 and 18 MV. Spatial
      distribution of ambient dose equivalent H*(10) per MU on the height of the
      linac's head and on the standard couch height for patients during the routine
      treatment, as well as relative contribution of gamma and neutron secondary
      radiation inside treatment room were evaluated.

PMID- 29036644
TI  - Roles of Female and Male Genotype in Post-Mating Responses in Drosophila
      melanogaster.
AB  - Mating induces a multitude of changes in female behavior, physiology, and gene
      expression. Interactions between female and male genotype lead to variation in
      post-mating phenotypes and reproductive success. So far, few female molecules
      responsible for these interactions have been identified. Here, we used Drosophila
      melanogaster from 5 geographically dispersed populations to investigate such
      female * male genotypic interactions at the female transcriptomic and phenotypic
      levels. Females from each line were singly-mated to males from the same 5 lines,
      for a total of 25 combinations. Reproductive output and refractoriness to re
      mating were assayed in females from the 25 mating combinations. Female * male
      genotypic interactions resulted in significant differences in these post-mating
      phenotypes. To assess whether female * male genotypic interactions affect the
      female post-mating transcriptome, next-generation RNA sequencing was performed on
      virgin and mated females at 5 to 6 h post-mating. Seventy-seven genes showed
      strong variation in mating-induced expression changes in a female * male genotype
      dependent manner. These genes were enriched for immune response and odorant
      binding functions, and for expression exclusively in the head. Strikingly,
      variation in post-mating transcript levels of a gene encoding a spermathecal
      endopeptidase was correlated with short-term egg production. The transcriptional
      variation found in specific functional classes of genes might be a read-out of
      female * male compatibility at a molecular level. Understanding the roles these
      genes play in the female post-mating response will be crucial to better
      understand the evolution of post-mating responses and related conflicts between
      the sexes.

PMID- 29036648
TI  - Coarse roots prevent declines in whole-tree non-structural carbohydrate pools
      during drought in an isohydric and an anisohydric species.
AB  - Predicted increases in the frequency and severity of droughts have led to a
      renewed focus on how plants physiologically adjust to low water availability. A
      popular framework for understanding plant responses to drought characterizes
      species along a spectrum from isohydry to anisohydry based on their regulation of
      gas exchange and leaf water potential under drying conditions. One prediction
      that arises from this theory is that plant drought responses may hinge, in part,
      on their usage of non-structural carbohydrate (NSC) pools. For example, trees
      that respond to drought by closing stomates (i.e., isohydric) are predicted to
      deplete NSC reserves to maintain metabolism, whereas plants that keep stomata
      open during water stress (i.e., anisohydric), may show little change or even
      increases in NSC concentration. However, empirical tests of this theory largely
      rely on aboveground measurements of NSC, ignoring the potentially conflicting
      responses of root NSC pools. We sought to test these predictions by subjecting
      potted saplings of Quercus alba L. (an anisohydric species) and Liriodendron
      tulipifera L. (an isohydric species) to a 6 week experimental drought. We found
      that stem NSC concentrations were depleted in the isohydric L. tulipifera but
      maintained in the anisohydric Q. alba-as predicted. However, when scaled to whole
      plant NSC content, the drought-induced decreases in stem NSCs in L. tulipifera
      were offset by increases in root NSCs (especially soluble sugars), resulting in
      no net change to whole-plant NSC content. Similarly, root sugars increased in Q.
      alba in response to drought. This increase was concurrent with declines in
      growth, suggesting a potential trade-off between allocation of photoassimilates
      to root sugars vs biomass during drought. Collectively, our results suggest that
      the responses of NSC in coarse roots can differ from stems, and indicate a
      prominent role of coarse roots in mitigating drought-induced declines in whole
      tree NSC pools.

PMID- 29036646
TI  - De novo, deleterious sequence variants that alter the transcriptional activity of
      the homeoprotein PBX1 are associated with intellectual disability and pleiotropic
      developmental defects.
AB  - We present eight patients with de novo, deleterious sequence variants in the PBX1
      gene. PBX1 encodes a three amino acid loop extension (TALE) homeodomain
      transcription factor that forms multimeric complexes with TALE and HOX proteins
      to regulate target gene transcription during development. As previously reported,
      Pbx1 homozygous mutant mice (Pbx1-/-) develop malformations and hypoplasia or
      aplasia of multiple organs, including the craniofacial skeleton, ear, branchial
      arches, heart, lungs, diaphragm, gut, kidneys, and gonads. Clinical findings
      similar to those in Pbx mutant mice were observed in all patients with varying
      expressivity and severity, including external ear anomalies, abnormal branchial
      arch derivatives, heart malformations, diaphragmatic hernia, renal hypoplasia and
      ambiguous genitalia. All patients but one had developmental delays. Previously
      reported patients with congenital anomalies affecting the kidney and urinary
      tract exhibited deletions and loss of function variants in PBX1. The sequence
      variants in our cases included missense substitutions adjacent to the PBX1
      homeodomain (p.Arg184Pro, p.Met224Lys, and p.Arg227Pro) or within the homeodomain
      (p.Arg234Pro, and p.Arg235Gln), whereas p.Ser262Glnfs*2, and p.Arg288* yielded
      truncated PBX1 proteins. Functional studies on five PBX1 sequence variants
      revealed perturbation of intrinsic, PBX-dependent transactivation ability and
      altered nuclear translocation, suggesting abnormal interactions between mutant
      PBX1 proteins and wild-type TALE or HOX cofactors. It is likely that the
      mutations directly affect the transcription of PBX1 target genes to impact
      embryonic development. We conclude that deleterious sequence variants in PBX1
      cause intellectual disability and pleiotropic malformations resembling those in
      Pbx1 mutant mice, arguing for strong conservation of gene function between these
      two species.

PMID- 29036649
TI  - The SMAD3 transcription factor binds complex RNA structures with high affinity.
AB  - Several members of the SMAD family of transcription factors have been reported to
      bind RNA in addition to their canonical double-stranded DNA (dsDNA) ligand. RNA
      binding by SMAD has the potential to affect numerous cellular functions that
      involve RNA. However, the affinity and specificity of this RNA binding activity
      has not been well characterized, which limits the ability to validate and
      extrapolate functional implications of this activity. Here we perform
      quantitative binding experiments in vitro to determine the ligand requirements
      for RNA binding by SMAD3. We find that SMAD3 binds poorly to single- and double
      stranded RNA, regardless of sequence. However, SMAD3 binds RNA with large
      internal loops or bulges with high apparent affinity. This apparent affinity
      matches that for its canonical dsDNA ligand, suggesting a biological role for RNA
      binding by SMAD3.

PMID- 29036651
TI  - Aureobasidium pullulans-cultured fluid induces IL-18 production, leading to Th1
      polarization during influenza A virus infection.
AB  - Several microbial molecules with pathogen-associated molecular patterns stimulate
      host innate immune responses. The innate immune system plays a crucial role in
      activating acquired immune response via cytokine production and antigen
      presentation. Previous studies have shown that Aureobasidium pullulans-cultured
      fluid (AP-CF), which contains beta-glucan, exhibits adjuvant activity and renders
      mice resistance to influenza A virus infection; however, the underlying mechanism
      remains elusive. In this study, we investigated the innate immune response to AP
      CF. We found that intraperitoneal administration of AP-CF increased the serum
      level of IL-18 and the number of splenic IFN-gamma producing CD4+ cells during
      influenza A virus infection. The adjuvant effect of AP-CF was distinct from that
      of alum, which is known to have the ability to stimulate a Th2 immune response.
      In addition, AP-CF injection barely increased the number of peritoneal
      neutrophils and inflammatory macrophages, whereas alum injection markedly
      increased the number of neutrophils and inflammatory macrophages, suggesting that
      AP-CF is a weak inducer of inflammation compared to alum. AP-CF induced IL-18
      production by DC2.4 cells, a dendritic cell line, and by peritoneal exudate cells
      that include peritoneal macrophages. Collectively, our findings indicate that AP
      CF is an adjuvant that promotes the Th1 response during influenza A virus
      infection.

PMID- 29036652
TI  - Adapting detection sensitivity based on evidence of irregular sinus arrhythmia to
      improve atrial fibrillation detection in insertable cardiac monitors.
AB  - Aims: Intermittent change in p-wave discernibility during periods of ectopy and
      sinus arrhythmia is a cause of inappropriate atrial fibrillation (AF) detection
      in insertable cardiac monitors (ICM). To address this, we developed and validated
      an enhanced AF detection algorithm. Methods and results: Atrial fibrillation
      detection in Reveal LINQ ICM uses patterns of incoherence in RR intervals and
      absence of P-wave evidence over a 2-min period. The enhanced algorithm includes P
      wave evidence during RR irregularity as evidence of sinus arrhythmia or ectopy to
      adaptively optimize sensitivity for AF detection. The algorithm was developed and
      validated using Holter data from the XPECT and LINQ Usability studies which
      collected surface electrocardiogram (ECG) and continuous ICM ECG over a 24-48 h
      period. The algorithm detections were compared with Holter annotations, performed
      by multiple reviewers, to compute episode and duration detection performance. The
      validation dataset comprised of 3187 h of valid Holter and LINQ recordings from
      138 patients, with true AF in 37 patients yielding 108 true AF episodes >=2-min
      and 449 h of AF. The enhanced algorithm reduced inappropriately detected episodes
      by 49% and duration by 66% with <1% loss in true episodes or duration. The
      algorithm correctly identified 98.9% of total AF duration and 99.8% of total
      sinus or non-AF rhythm duration. The algorithm detected 97.2% (99.7% per-patient
      average) of all AF episodes >=2-min, and 84.9% (95.3% per-patient average) of
      detected episodes involved AF. Conclusion: An enhancement that adapts sensitivity
      for AF detection reduced inappropriately detected episodes and duration with
      minimal reduction in sensitivity.

PMID- 29036650
TI  - Characteristic arrangement of nucleosomes is predictive of chromatin interactions
      at kilobase resolution.
AB  - High-throughput chromosome conformation capture (3C) technologies, such as Hi-C,
      have made it possible to survey 3D genome structure. However, obtaining 3D
      profiles at kilobase resolution at low cost remains a major challenge. Therefore,
      we herein present an algorithm for precise identification of chromatin
      interaction sites at kilobase resolution from MNase-seq data, termed chromatin
      interaction site detector (CISD), and a CISD-based chromatin loop predictor
      (CISD_loop) that predicts chromatin-chromatin interactions (CCIs) from low
      resolution Hi-C data. We show that the predictions of CISD and CISD_loop overlap
      closely with chromatin interaction analysis by paired-end tag sequencing (ChIA
      PET) anchors and loops, respectively. The validity of CISD/CISD_loop was further
      supported by a 3C assay at about 5 kb resolution. Finally, we demonstrate that
      only modest amounts of MNase-seq and Hi-C data are sufficient to achieve
      ultrahigh resolution CCI maps. Our results suggest that CCIs may result in
      characteristic nucleosomes arrangement patterns flanking the interaction sites,
      and our algorithms may facilitate precise and systematic investigations of CCIs
      on a larger scale than hitherto have been possible.

PMID- 29036653
TI  - miRCarta: a central repository for collecting miRNA candidates.
AB  - The continuous increase of available biological data as consequence of modern
      high-throughput technologies poses new challenges for analysis techniques and
      database applications. Especially for miRNAs, one class of small non-coding RNAs,
      many algorithms have been developed to predict new candidates from next
      generation sequencing data. While the amount of publications describing novel
      miRNA candidates keeps steadily increasing, the current gold standard database
      for miRNAs - miRBase - has not been updated since June 2014. As a result,
      publications describing new miRNA candidates in the last three to five years
      might have a substantial overlap of candidates without noticing. With miRCarta we
      implemented a database to collect novel miRNA candidates and augment the
      information provided by miRBase. In the first stage, miRCarta is thought to be a
      highly sensitive collection of potential miRNA candidates with a high degree of
      analysis functionality, annotations and details on each miRNA. We added-besides
      the full content of the miRBase-12,857 human miRNA precursors to miRCarta. Users
      can match their own predictions to the entries of miRCarta to reduce potential
      redundancies in their studies. miRCarta provides the most comprehensive
      collection of human miRNAs and miRNA candidates to form a basis for further
      refinement and validation studies. The database is freely accessible at
      https://mircarta.cs.uni-saarland.de/.

PMID- 29036654
TI  - Detection of expanded RNA repeats using thermostable group II intron reverse
      transcriptase.
AB  - Cellular accumulation of repetitive RNA occurs in several dominantly-inherited
      genetic disorders. Expanded CUG, CCUG or GGGGCC repeats are expressed in myotonic
      dystrophy type 1 (DM1), myotonic dystrophy type 2 (DM2), or familial amyotrophic
      lateral sclerosis, respectively. Expanded repeat RNAs (ER-RNAs) exert a toxic
      gain-of-function and are prime therapeutic targets in these diseases. However,
      efforts to quantify ER-RNA levels or monitor knockdown are confounded by stable
      structure and heterogeneity of the ER-RNA tract and background signal from non
      expanded repeats. Here, we used a thermostable group II intron reverse
      transcriptase (TGIRT-III) to convert ER-RNA to cDNA, followed by quantification
      on slot blots. We found that TGIRT-III was capable of reverse transcription (RTn)
      on enzymatically synthesized ER-RNAs. By using conditions that limit cDNA
      synthesis from off-target sequences, we observed hybridization signals on cDNA
      slot blots from DM1 and DM2 muscle samples but not from healthy controls. In
      transgenic mouse models of DM1 the cDNA slot blots accurately reflected the
      differences of ER-RNA expression across different transgenic lines, and showed
      therapeutic reductions in skeletal and cardiac muscle, accompanied by
      improvements of the DM1-associated splicing defects. TGIRT-III was also active on
      CCCCGG- and GGGGCC-repeats, suggesting that ER-RNA analysis is feasible for
      several repeat expansion disorders.

PMID- 29036655
TI  - MFIB: a repository of protein complexes with mutual folding induced by binding.
AB  - Motivation: It is commonplace that intrinsically disordered proteins (IDPs) are
      involved in crucial interactions in the living cell. However, the study of
      protein complexes formed exclusively by IDPs is hindered by the lack of data and
      such analyses remain sporadic. Systematic studies benefited other types of
      protein-protein interactions paving a way from basic science to therapeutics; yet
      these efforts require reliable datasets that are currently lacking for
      synergistically folding complexes of IDPs. Results: Here we present the Mutual
      Folding Induced by Binding (MFIB) database, the first systematic collection of
      complexes formed exclusively by IDPs. MFIB contains an order of magnitude more
      data than any dataset used in corresponding studies and offers a wide coverage of
      known IDP complexes in terms of flexibility, oligomeric composition and protein
      function from all domains of life. The included complexes are grouped using a
      hierarchical classification and are complemented with structural and functional
      annotations. MFIB is backed by a firm development team and infrastructure, and
      together with possible future community collaboration it will provide the
      cornerstone for structural and functional studies of IDP complexes. Availability
      and implementation: MFIB is freely accessible at http://mfib.enzim.ttk.mta.hu/.
      The MFIB application is hosted by Apache web server and was implemented in PHP.
      To enrich querying features and to enhance backend performance a MySQL database
      was also created. Contact: simon.istvan@ttk.mta.hu, meszaros.balint@ttk.mta.hu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29036656
TI  - RELATIVE BIOLOGICAL EFFECTIVENESS OF NEUTRONS DERIVED FROM THE EXCESS RELATIVE
      RISK MODEL WITH THE ATOMIC BOMB SURVIVORS DATA MANAGED BY HIROSHIMA UNIVERSITY.
AB  - According to an analysis of the Life Span Study cohort data conducted by the
      Radiation Effects Research Foundation in Hiroshima and Nagasaki, the sex-averaged
      excess relative risk (ERR) of all solid cancers was 0.42 Gy-Eq-1. On the other
      hand, analysis of the atomic bomb survivors (ABS) cohort data at Hiroshima
      University indicated the ERR value was 0.28 Gy-Eq-1 in Hiroshima. In both cases,
      initial radiation doses were derived from the dosimetry system DS02, in which the
      relative biological effectiveness (RBE) of neutrons was assumed to be a constant
      value of 10. To clarify the validity of the RBE, the authors investigated the
      possibility of different contributions of neutrons by using the ABS. Although
      there were no statistically significant differences among the estimated value of
      RBE (=65) and the ordinal value (=10), the corresponding ERR decreased by 30%,
      which might affect the interpretation of radiation health assessments.

PMID- 29036657
TI  - Genomic Admixture Between Locally Adapted Populations of Arabidopsis thaliana
      (mouse ear cress): Evidence of Optimal Genetic Outcrossing Distance.
AB  - Admixture can break up divergent genetic architectures between populations,
      resulting in phenotypic novelty and generating raw material for environmental
      selection. The contribution of admixture to progeny trait variation and fitness
      varies based on the degree of genetic isolation between the parental populations,
      for which most studies have used geographic distance as a proxy. A novel approach
      is to estimate optimal crossing distance using the adaptive genetic distance
      between mates estimated from loci that contribute directly to local adaptation.
      Here, we aim to understand the effect of admixture on disrupting local adaptation
      of ecotypes of Arabidopsis thaliana separated along gradients of geographic,
      background, and locally adaptive genetic distances. We created experimental F1
      hybrids between ecotypes that vary in geographic distance and used SNP data to
      estimate background (putatively neutral) and adaptive genetic distance. Hybrids
      were grown under controlled conditions, and fitness, growth, and phenology traits
      were measured. The different traits measured showed a clear effect of adaptive
      genetic distance, but not geographic distance. The earliest bolting hybrids were
      intermediate in the adaptive genetic distance between their parents, and also had
      higher biomass and fitness in terms of fruit and seed production. Our results
      suggest that disruption of locally adaptive genomic loci decreases the
      performance of offspring between distantly related parents, but that crosses
      between very closely related parents also reduce performance, likely through the
      expression of deleterious recessive alleles. We conclude that during admixture,
      selection may have to balance the consequences of disrupting local adaption while
      also avoiding inbreeding depression.

PMID- 29036658
TI  - Dying piece by piece: carbohydrate dynamics in aspen (Populus tremuloides)
      seedlings under severe carbon stress.
AB  - Carbon starvation as a mechanism of tree mortality is poorly understood. We
      exposed seedlings of aspen (Populus tremuloides) to complete darkness at 20 or 28
      degrees C to identify minimum non-structural carbohydrate (NSC) concentrations
      at which trees die and to see if these levels vary between organs or with
      environmental conditions. We also first grew seedlings under different shade
      levels to determine if size affects survival time under darkness due to changes
      in initial NSC concentration and pool size and/or respiration rates. Darkness
      treatments caused a gradual dieback of tissues. Even after half the stem had
      died, substantial starch reserves were still present in the roots (1.3-3% dry
      weight), indicating limitations to carbohydrate remobilization and/or transport
      during starvation in the absence of water stress. Survival time decreased with
      increased temperature and with increasing initial shade level, which was
      associated with smaller biomass, higher respiration rates, and initially smaller
      NSC pool size. Dead tissues generally contained no starch, but sugar
      concentrations were substantially above zero and differed between organs (~2% in
      stems up to ~7.5% in leaves) and, at times, between temperature treatments and
      initial, pre-darkness shade treatments. Minimum root NSC concentrations were
      difficult to determine because dead roots quickly began to decompose, but we
      identify 5-6% sugar as a potential threshold for living roots. This variability
      may complicate efforts to identify critical NSC thresholds below which trees
      starve.

PMID- 29036659
TI  - Derivation of Occupational Thresholds of Toxicological Concern for Systemically
      Acting Noncarcinogenic Organic Chemicals.
AB  - Many substances in workplace do not have occupational exposure limits. The
      threshold of toxicological concern (TTC) principle is part of the hierarchy of
      approaches useful in occupational health risk assessment. The aim of this study
      was to derive occupational TTCs (OTTCs) reflecting the airborne concentrations
      below which no significant risk to workers would be anticipated. A reference
      dataset consisting of the 8-h threshold limit values-Time-Weighted Average for
      280 organic substances was compiled. Each substance was classified into low
      (class I), intermediate (class II), or high (class III) hazard categories as per
      Cramer rules. For each chemical, n-octanol:water partition coefficient and vapor
      pressure along with the molecular weight were used to predict the blood:air
      partition coefficient. The blood:air partition coefficient along with data on
      water solubility and ventilation rate allowed the prediction of pulmonary
      retention factor and absorbed dose in workers. For each Cramer class, the
      distribution of the predicted doses was analyzed to identify the various
      percentile values corresponding to the OTTC. Accordingly, for Cramer classes I
      III, the OTTCs derived in this study correspond to 0.15, 0.0085, and 0.006
      mmol/d, respectively, at the 10th percentile level, while these values were 1.5,
      0.09 and 0.03 mmol/d at the 25th percentile level. The proposed OTTCs are not
      meant to replace the traditional occupational exposure limits, but can be used in
      data-poor situations along with exposure estimates to support screening level
      risk assessment and prioritization.

PMID- 29036660
TI  - MCNPX CALCULATIONS OF SPECIFIC ABSORBED FRACTIONS IN SOME ORGANS OF THE HUMAN
      BODY DUE TO APPLICATION OF 133Xe, 99mTc and 81mKr RADIONUCLIDES.
AB  - Monte Carlo simulations were performed to evaluate treatment doses with wide
      spread used radionuclides 133Xe, 99mTc and 81mKr. These different radionuclides
      are used in perfusion or ventilation examinations in nuclear medicine and as
      indicators for cardiovascular and pulmonary diseases. The objective of this work
      was to estimate the specific absorbed fractions in surrounding organs and
      tissues, when these radionuclides are incorporated in the lungs. For this purpose
      a voxel thorax model has been developed and compared with the ORNL phantom. All
      calculations and simulations were performed by means of the MCNP5/X code.

PMID- 29036661
TI  - The impact of the Brazilian Family Health Strategy and the conditional cash
      transfer on tuberculosis treatment outcomes in Rio de Janeiro: an individual
      level analysis of secondary data.
AB  - Background: Unsuccessful tuberculosis outcomes are frequent; bold policies are
      needed to end the tuberculosis (TB) epidemic to attain the third Sustainable
      Development Goal (SDG) by 2030. We examined the effect of the Family Health
      Strategy (FHS) and its interactions with the conditional cash transfer programme
      (CTP) on TB outcomes in Rio de Janeiro, Brazil. Methods: We performed individual
      based analyses of a database resulting from deterministic and probabilistic
      linkages of the TB information system, FHS registries and CTP payrolls. Patients
      >=15 years old treated with the standard RHZE regimen were included. The rates of
      successful outcomes were analysed according to coverage by FHS. Effects from the
      CTP and its interactions with the FHS were examined among the poorest. Results:
      FHS coverage increased the likelihood for successful outcomes by 14% (12-17%)
      among 13 482 new cases, and by 35% (25-47%) among 1880 retreatment cases. The CTP
      had an independent effect but no interaction with the FHS among the poorest.
      Conclusions: This is the first individual-based study to show a relevant
      protection of poor urban communities regarding patient-important health outcomes
      by the Brazilian FHS and CTP. These findings support strategies of universal
      health coverage, primary care strengthening and social protection to achieve a
      major SDG.

PMID- 29036665
TI  - Corrigendum.

PMID- 29036663
TI  - Metabolomics and Biochemical Approaches Link Salicylic Acid Biosynthesis to
      Cyanogenesis in Peach Plants.
AB  - Despite the long-established importance of salicylic acid (SA) in plant stress
      responses and other biological processes, its biosynthetic pathways have not been
      fully characterized. The proposed synthesis of SA originates from chorismate by
      two distinct pathways: the isochorismate and phenylalanine (Phe) ammonia-lyase
      (PAL) pathways. Cyanogenesis is the process related to the release of hydrogen
      cyanide from endogenous cyanogenic glycosides (CNglcs), and it has been linked to
      plant plasticity improvement. To date, however, no relationship has been
      suggested between the two pathways. In this work, by metabolomics and biochemical
      approaches (including the use of [13C]-labeled compounds), we provide strong
      evidences showing that CNglcs turnover is involved, at least in part, in SA
      biosynthesis in peach plants under control and stress conditions. The main CNglcs
      in peach are prunasin and amygdalin, with mandelonitrile (MD), synthesized from
      phenylalanine, controlling their turnover. In peach plants MD is the intermediary
      molecule of the suggested new SA biosynthetic pathway and CNglcs turnover,
      regulating the biosynthesis of both amygdalin and SA. MD-treated peach plants
      displayed increased SA levels via benzoic acid (one of the SA precursors within
      the PAL pathway). MD also provided partial protection against Plum pox virus
      infection in peach seedlings. Thus, we propose a third pathway, an alternative to
      the PAL pathway, for SA synthesis in peach plants.

PMID- 29036664
TI  - Trigger Point Diagnosis: At Last, the First Word on Consensus.

PMID- 29036666
TI  - Do Israeli health promoting schools contribute to students' healthy eating and
      physical activity habits?
AB  - The Israeli Health Promoting School Network (HPSN) is actively committed to
      enhancing a healthy lifestyle for the entire school population. This study aimed
      to explore the contribution of school participation in the HPSN and students'
      individual characteristics to healthy eating and physical activity habits among
      Israeli school children aged 10-12 years. A cross-sectional survey was conducted
      among 4166 students in grades 4-6 from 28 schools. The schools were selected from
      a sample of HPSN affiliated and non-HPSN schools. The contribution of individual
      characteristics (grade, gender and subjective self-reported health education
      activities at school) and school characteristics (school type, population group,
      deprivation score) to healthy eating and physical activity habits was analyzed
      using multi-level hierarchical models. Multi-level analysis indicated that
      student's individual characteristic was significantly associated with healthy
      eating and physical activity habits. The subjective self-reported health
      education received at school was statistically significant factor associated with
      students' health behaviors. The school's affiliation with the HPSN was not
      associated with higher healthy eating and physical activity scores after
      adjusting for individual factors. These findings suggest that Israeli HPSN
      schools do not contribute to children's health behaviors more than other schools.
      Therefore, health promoting activities in HPSN schools need to be improved to
      justify their recognition as members of the HPS network and to fulfill their
      mission.

PMID- 29036662
TI  - PARP2 controls double-strand break repair pathway choice by limiting 53BP1
      accumulation at DNA damage sites and promoting end-resection.
AB  - Double strand breaks (DSBs) are one of the most toxic lesions to cells. DSB
      repair by the canonical non-homologous end-joining (C-EJ) pathway involves minor,
      if any, processing of the broken DNA-ends, whereas the initiation of DNA
      resection channels the broken-ends toward DNA repair pathways using various
      lengths of homology. Mechanisms that control the resection initiation are thus
      central to the regulation to the choice of DSB repair pathway. Therefore,
      understanding the mechanisms which regulate the initiation of DNA end-resection
      is of prime importance. Our findings reveal that poly(ADP-ribose) polymerase 2
      (PARP2) is involved in DSBR pathway choice independently of its PAR synthesis
      activity. We show that PARP2 favors repair by homologous recombination (HR),
      single strand annealing (SSA) and alternative-end joining (A-EJ) rather than the
      C-EJ pathway and increases the deletion sizes at A-EJ junctions. We demonstrate
      that PARP2 specifically limits the accumulation of the resection barrier factor
      53BP1 at DNA damage sites, allowing efficient CtIP-dependent DNA end-resection.
      Collectively, we have identified a new PARP2 function, independent of its PAR
      synthesis activity, which directs DSBs toward resection-dependent repair
      pathways.

PMID- 29036667
TI  - DISNOR: a disease network open resource.
AB  - DISNOR is a new resource that aims at exploiting the explosion of data on the
      identification of disease-associated genes to assemble inferred disease pathways.
      This may help dissecting the signaling events whose disruption causes the
      pathological phenotypes and may contribute to build a platform for precision
      medicine. To this end we combine the gene-disease association (GDA) data
      annotated in the DisGeNET resource with a new curation effort aimed at populating
      the SIGNOR database with causal interactions related to disease genes with the
      highest possible coverage. DISNOR can be freely accessed at
      http://DISNOR.uniroma2.it/ where >3700 disease-networks, linking ~2600 disease
      genes, can be explored. For each disease curated in DisGeNET, DISNOR links
      disease genes by manually annotated causal relationships and offers an intuitive
      visualization of the inferred 'patho-pathways' at different complexity levels.
      User-defined gene lists are also accepted in the query pipeline. In addition, for
      each list of query genes-either annotated in DisGeNET or user-defined-DISNOR
      performs a gene set enrichment analysis on KEGG-defined pathways or on the lists
      of proteins associated with the inferred disease pathways. This function offers
      additional information on disease-associated cellular pathways and disease
      similarity.

PMID- 29036668
TI  - Neurobiological Commonalities and Distinctions Among Three Major Psychiatric
      Diagnostic Categories: A Structural MRI Study.
AB  - BACKGROUND: Schizophrenia (SZ), bipolar disorder (BD), and major depressive
      disorder (MDD) are distinct diagnostic categories in current psychiatric
      nosology, yet there is increasing evidence for shared clinical and biological
      features in these disorders. No previous studies have examined brain structural
      features concurrently in these 3 disorders. The aim of this study was to identify
      the extent of shared and distinct brain alterations in SZ, BD, and MDD. We
      examined gray matter (GM) volume and white matter (WM) integrity in a total of
      485 individuals (135 with SZ, 86 with BD, 108 with MDD, and 156 healthy controls
      [HC]) who underwent high-resolution structural magnetic resonance imaging (MRI)
      and diffusion tensor imaging (DTI) at a single site. RESULTS: Significant 4-group
      (SZ, BD, MDD, and HC groups) differences (P < .05, corrected) in GM volumes were
      found primarily in the paralimbic and heteromodal corticies. Post hoc analyses
      showed that the SZ, BD, and MDD groups shared GM volume decreases in 87.9% of the
      total regional volume with significant 4-group differences. Significant 4-group
      differences in WM integrity (P < .05 corrected) were found in callosal, limbic
      paralimbic-hetermodal, cortico-cortical, thalamocortical and cerebellar WM. Post
      hoc analyses revealed that the SZ and BD groups shared WM alterations in all
      regions, while WM alterations were not observed with MDD. CONCLUSIONS: Our
      findings of common alterations in SZ, BD, and MDD support the presence of core
      neurobiological disruptions in these disorders and suggest that neural structural
      distinctions between these disorders may be less prominent than initially
      postulated, particularly between SZ and BD.

PMID- 29036670
TI  - Catalytic and structural properties of pheophytinase, the phytol esterase
      involved in chlorophyll breakdown.
AB  - During leaf senescence and fruit ripening, chlorophyll is degraded in a multistep
      pathway into linear tetrapyrroles called phyllobilins. A key feature of
      chlorophyll breakdown is the removal of the hydrophobic phytol chain that renders
      phyllobilins water soluble, an important prerequisite for their ultimate storage
      in the vacuole of senescent cells. Chlorophyllases had been considered for more
      than a century to catalyze dephytylation in vivo; however, this was recently
      refuted. Instead, pheophytinase was discovered as a genuine in vivo phytol
      hydrolase. While chlorophyllase acts rather unspecifically towards different
      porphyrin substrates, pheophytinase was shown to specifically dephytylate
      pheophytin, namely Mg-free chlorophyll. The aim of this work was to elucidate in
      detail the biochemical and structural properties of pheophytinase. By testing
      different porphyrin substrates with recombinant pheophytinase from Arabidopsis
      thaliana we show that pheophytinase has high specificity for the acid moiety of
      the ester bond, namely the porphyrin ring, while the nature of the alcohol,
      namely the phytol chain in pheophytin, is irrelevant. In silico modelling of the
      3-dimensional structure of pheophytinase and subsequent analysis of site-directed
      pheophytinase mutant forms allowed the identification of the serine, histidine,
      and aspartic acid residues that compose the catalytic triad, a classical feature
      of serine-type hydrolases to which both pheophytinase and chlorophyllase belong.
      Based on substantial structural differences in the models of Arabidopsis
      pheophytinase and chlorophyllase 1, we discuss potential differences in the
      catalytic properties of these two phytol hydrolases.

PMID- 29036669
TI  - Comparative genome and transcriptome analyses reveal adaptations to opportunistic
      infections in woody plant degrading pathogens of Botryosphaeriaceae.
AB  - Botryosphaeriaceae are an important fungal family that cause woody plant diseases
      worldwide. Recent studies have established a correlation between environmental
      factors and disease expression; however, less is known about factors that trigger
      these diseases. The current study reports on the 43.3 Mb de novo genome of
      Lasiodiplodia theobromae and five other genomes of Botryosphaeriaceae pathogens.
      Botryosphaeriaceous genomes showed an expansion of gene families associated with
      cell wall degradation, nutrient uptake, secondary metabolism and membrane
      transport, which contribute to adaptations for wood degradation. Transcriptome
      analysis revealed that genes involved in carbohydrate catabolism, pectin, starch
      and sucrose metabolism, and pentose and glucuronate interconversion pathways were
      induced during infection. Furthermore, genes in carbohydrate-binding modules,
      lysine motif domain and the glycosyl hydrolase gene families were induced by high
      temperature. Among these genes, overexpression of two selected putative
      lignocellulase genes led to increased virulence in the transformants. These
      results demonstrate the importance of high temperatures in opportunistic
      infections. This study also presents a set of Botryosphaeriaceae-specific
      effectors responsible for the identification of virulence-related pathogen
      associated molecular patterns and demonstrates their active participation in
      suppressing hypersensitive responses. Together, these findings significantly
      expand our understanding of the determinants of pathogenicity or virulence in
      Botryosphaeriaceae and provide new insights for developing management strategies
      against them.

PMID- 29036671
TI  - CRISPR/Cas9-mediated gene knockout is insensitive to target copy number but is
      dependent on guide RNA potency and Cas9/sgRNA threshold expression level.
AB  - CRISPR/Cas9 is a powerful gene editing tool for gene knockout studies and
      functional genomic screens. Successful implementation of CRISPR often requires
      Cas9 to elicit efficient target knockout in a population of cells. In this study,
      we investigated the role of several key factors, including variation in target
      copy number, inherent potency of sgRNA guides, and expression level of Cas9 and
      sgRNA, in determining CRISPR knockout efficiency. Using isogenic, clonal cell
      lines with variable copy numbers of an EGFP transgene, we discovered that CRISPR
      knockout is relatively insensitive to target copy number, but is highly dependent
      on the potency of the sgRNA guide sequence. Kinetic analysis revealed that most
      target mutation occurs between 5 and 10 days following Cas9/sgRNA transduction,
      while sgRNAs with different potencies differ by their knockout time course and by
      their terminal-phase knockout efficiency. We showed that prolonged, low level
      expression of Cas9 and sgRNA often fails to elicit target mutation, particularly
      if the potency of the sgRNA is also low. Our findings provide new insights into
      the behavior of CRISPR/Cas9 in mammalian cells that could be used for future
      improvement of this platform.

PMID- 29036672
TI  - Convergence and Divergence of Brain Network Dysfunction in Deficit and Non
      deficit Schizophrenia.
AB  - Deficit schizophrenia (DS), characterized by primary and enduring negative
      symptoms, has been considered as a pathophysiologically distinct schizophrenic
      subgroup. Neuroimaging characteristics of DS, especially functional brain network
      architecture, remain largely unknown. Resting-state functional magnetic resonance
      imaging and graph theory approaches were employed to investigate the topological
      organization of whole-brain functional networks of 114 male participants
      including 33 DS, 41 non-deficit schizophrenia (NDS) and 40 healthy controls
      (HCs). At the whole-brain level, both the NDS and DS group exhibited lower local
      efficiency (Eloc) than the HC group, implying the reduction of local
      specialization of brain information processing (reduced functional segregation).
      The DS, but not NDS group, exhibited enhanced parallel information transfer
      (enhanced functional integration) as determined by smaller characteristic path
      length (Lp) and higher global efficiency (Eglob). The Lp and Eglob presented
      significant correlations with Brief Psychiatric Rating Scale (BPRS) total score
      in the DS group. At the nodal level, both the NDS and DS groups showed higher
      functional connectivity in the inferior frontal gyrus and hippocampus, and lower
      connectivity in the visual areas and striatum than the controls. The DS group
      exhibited higher nodal connectivity in the right inferior temporal gyrus than the
      NDS and HC group. The diminished expression of Scale for the Assessment of
      Negative Symptoms (SANS) subfactors negatively correlated with nodal connectivity
      of right putamen, while asociality/amotivation positively correlated with right
      hippocampus across whole patients. We highlighted the convergence and divergence
      of brain functional network dysfunctions in patients with DS and NDS, which
      provides crucial insights into pathophysiological mechanisms of the 2
      schizophrenic subtypes.

PMID- 29036674
TI  - Detecting and characterizing microRNAs of diverse genomic origins via miRvial.
AB  - MicroRNAs form an essential class of post-transcriptional gene regulator of
      eukaryotic species, and play critical parts in development and disease and stress
      responses. MicroRNAs may originate from various genomic loci, have structural
      characteristics, and appear in canonical or modified forms, making them subtle to
      detect and analyze. We present miRvial, a robust computational method and
      companion software package that supports parameter adjustment and visual
      inspection of candidate microRNAs. Extensive results comparing miRvial and six
      existing microRNA finding methods on six model organisms, Mus musculus,
      Drosophila melanogaste, Arabidopsis thaliana, Oryza sativa, Physcomitrella patens
      and Chlamydomonas reinhardtii, demonstrated the utility and rigor of miRvial in
      detecting novel microRNAs and characterizing features of microRNAs. Experimental
      validation of several novel microRNAs in C. reinhardtii that were predicted by
      miRvial but missed by the other methods illustrated the superior performance of
      miRvial over the existing methods. miRvial is open source and available at
      https://github.com/SystemsBiologyOfJianghanUniversity/miRvial.

PMID- 29036675
TI  - INDOOR RADON, THORON AND THEIR PROGENY CONCENTRATIONS IN HIGH THORON RURAL SERBIA
      ENVIRONMENTS.
AB  - This article deals with the variation of radon (Rn), thoron (Tn) and their
      progeny concentrations expressed in terms of equilibrium equivalent
      concentrations (EERC and EETC), in 40 houses, in four villages of Sokobanja
      municipality, Southern Serbia. Two types of passive detectors were used: (1)
      discriminative radon-thoron detector for simultaneous Rn and Tn gases
      measurements and (2) direct Tn and Rn progeny sensors (DRPS/DTPS) for measuring
      Rn and Tn progeny concentrations. Detectors were exposed simultaneously for a
      single period of 12 months. Variations of Tn and EETC appear higher than those of
      Rn and EERC. Analysis of the spatial variation of the measured concentrations is
      also reported. This work is part of a wider survey of Rn, Tn and their progeny
      concentrations in indoor environments throughout the Balkan region started in
      2011 year.

PMID- 29036673
TI  - Enhanced Desiccation Tolerance in Mature Cultures of the Streptophytic Green Alga
      Zygnema circumcarinatum Revealed by Transcriptomics.
AB  - Desiccation tolerance is commonly regarded as one of the key features for the
      colonization of terrestrial habitats by green algae and the evolution of land
      plants. Extensive studies, focused mostly on physiology, have been carried out
      assessing the desiccation tolerance and resilience of the streptophytic genera
      Klebsormidium and Zygnema. Here we present transcriptomic analyses of Zygnema
      circumcarinatum exposed to desiccation stress. Cultures of Z. circumcarinatum
      grown in liquid medium or on agar plates were desiccated at ~86% relative air
      humidity until the effective quantum yield of PSII [Y(II)] ceased. In general,
      the response to dehydration was much more pronounced in Z. circumcarinatum
      cultured in liquid medium for 1 month compared with filaments grown on agar
      plates for 7 and 12 months. Culture on solid medium enables the alga to acclimate
      to dehydration much better and an increase in desiccation tolerance was clearly
      correlated to increased culture age. Moreover, gene expression analysis revealed
      that photosynthesis was strongly repressed upon desiccation treatment in the
      liquid culture while only minor effects were detected in filaments cultured on
      agar plates for 7 months. Otherwise, both samples showed induction of stress
      protection mechanisms such as reactive oxygen species scavenging (early light
      induced proteins, glutathione metabolism) and DNA repair as well as the
      expression of chaperones and aquaporins. Additionally, Z. circumcarinatum
      cultured in liquid medium upregulated sucrose-synthesizing enzymes and strongly
      induced membrane modifications in response to desiccation stress. These results
      corroborate the previously described hardening and associated desiccation
      tolerance in Zygnema in response to seasonal fluctuations in water availability.

PMID- 29036677
TI  - Preliminary Results of Radon Survey in the Kindergartens of V4 Countries.
AB  - The measurements of radon concentration were carried out in kindergartens of V4
      countries (Hungary, Poland and Slovakia). RSKS detectors (Radosys Ltd., Hungary)
      were used for integrating measurement in indoor air. In total, 67 rooms in 20
      kindergartens were measured. The survey was carried out in two periods from
      October 2015 to March 2016. The results show that radon concentration is less
      than 300 Bq m-3 in approximately 86.0% of cases in the first period and in 82.1%
      of cases in second period. However, rooms in kindergartens with radon
      concentration exceeding 1000 Bq m-3 were found in Slovakia.

PMID- 29036676
TI  - Anti-CRISPRdb: a comprehensive online resource for anti-CRISPR proteins.
AB  - CRISPR-Cas is a tool that is widely used for gene editing. However, unexpected
      off-target effects may occur as a result of long-term nuclease activity. Anti
      CRISPR proteins, which are powerful molecules that inhibit the CRISPR-Cas system,
      may have the potential to promote better utilization of the CRISPR-Cas system in
      gene editing, especially for gene therapy. Additionally, more in-depth research
      on these proteins would help researchers to better understand the co-evolution of
      bacteria and phages. Therefore, it is necessary to collect and integrate data on
      various types of anti-CRISPRs. Herein, data on these proteins were manually
      gathered through data screening of the literatures. Then, the first online
      resource, anti-CRISPRdb, was constructed for effectively organizing these
      proteins. It contains the available protein sequences, DNA sequences, coding
      regions, source organisms, taxonomy, virulence, protein interactors and their
      corresponding three-dimensional structures. Users can access our database at
      http://cefg.uestc.edu.cn/anti-CRISPRdb/ without registration. We believe that the
      anti-CRISPRdb can be used as a resource to facilitate research on anti-CRISPR
      proteins and in related fields.

PMID- 29036678
TI  - Country of residence, gender equality and victim blaming attitudes about partner
      violence: a multilevel analysis in EU.
AB  - Background: Intimate partner violence against women (IPVAW) is a global and
      preventable public health problem. Public attitudes, such as victim-blaming, are
      important for our understanding of differences in the occurrence of IPVAW, as
      they contribute to its justification. In this paper, we focus on victim-blaming
      attitudes regarding IPVAW within the EU and we apply multilevel analyses to
      identify contextual determinants of victim-blaming attitudes. We investigate both
      the general contextual effect of the country and the specific association between
      country level of gender equality and individual victim-blaming attitudes, as well
      as to what extend a possible general contextual effect was explained by county
      level gender equality. Methods: We analyzed data from 26 800 respondents from 27
      member states of the European Union who responded to a survey on public
      perceptions of domestic violence. We applied multilevel logistic regression
      analysis and measures of variance (intra-class correlation (ICC)) were
      calculated, as well as the discriminatory accuracy by calculating the area under
      the receiver operator characteristic curve. Results: Over and above individual
      characteristics, about 15% of the individual variance in the propensity for
      having victim-blaming attitudes was found at the country level, and country level
      of gender equality did not affect the general contextual effect (i.e. ICC) of the
      country on individual victim-blaming attitudes. Conclusion: The present study
      shows that there are important between-country differences in victim-blaming
      attitudes that cannot be explained by differences in individual-level
      demographics or in gender equality at the country level. More research on
      attitudes towards IPVAW is needed.

PMID- 29036679
TI  - Human recombinant Fab fragment from combinatorial libraries of a B-cell lymphoma
      patient recognizes core protein of chondroitin sulphate proteoglycan 4.
AB  - CD antigens are well known as therapeutic targets of B-cell lymphoma. To isolate
      therapeutic antibodies that recognize novel targets other than CD antigens, we
      constructed a phage display combinatorial antibody Fab library from bone marrow
      lymphocytes of B-cell lymphoma patient. To eliminate antibodies reactive with
      known B-cell lymphoma antigen, non-hematopoietic and patient's sera reactive
      HeLaS3 cells was selected as a target of whole cell panning. Five rounds of
      panning against live HeLaS3 cells retrieved single Fab clone, termed AHSA
      (Antibody to HeLa Surface Antigen). Using phage display random peptide library,
      LSYLEP was identified as an epitope sequence of AHSA. LC-MS/MS analysis of AHSA
      precipitated HeLaS3 cell lysates detected several fragments corresponding to the
      sequence of chondroitin sulphate proteoglycan 4 (CSPG4) core protein. Since
      LSYLEP sequence was at the position of 313-318 of CSPG4, we considered that CSPG4
      was AHSA-associated antigen. Double staining of CSPG4-postive MDA-MB-435S cells
      with AHSA and anti-CSPG4 rabbit antibody showed identical staining position, and
      reduced AHSA reactivity was observed in CSPG4-siRNA treated MDA-MB-435S cells. In
      conclusion, we retrieved a human Fab from antibody library of B-cell lymphoma
      patient, and identified CSPG4 as a recognizing antigen. AHSA may have potential
      benefits for development of CSPG4-targeting theranostics for B-cell lymphoma.

PMID- 29036680
TI  - Factors Associated with Opioid Initiation in OEF/OIF/OND Veterans with Traumatic
      Brain Injury.
AB  - Objective: These analyses examined opioid initiation and chronic use among Iraq
      (OIF) and Afghanistan (OEF/OND) veterans with a new diagnosis of traumatic brain
      injury (TBI) in the Veterans Health Administration (VHA). Methods: Data were
      obtained from national VHA data repositories. Analyses included OEF/OIF/OND
      veterans with a new TBI diagnosis in 2010-2012 who used the VHA at least twice,
      had not received a VHA opioid prescription in the 365 days before diagnosis, and
      had at least 365 days of data available after TBI diagnosis. Results: Analyses
      included 35,621 veterans. Twenty-one percent initiated opioids; among new
      initiators, 23% used chronically. The mean dose was 24.0 mg morphine equivalent
      dose (MED) daily (SD = 24.26); mean days supplied was 60.52 (SD = 74.69).
      Initiation was significantly associated with age 36-45 years (odds ratio [OR] =
      1.09, 95% CI = 1.01-1.17, P = 0.04), female gender (OR = 1.22, P < 0.001), having
      back pain (OR = 1.38, P < 0.0001), arthritis/joint pain (OR = 1.24, P < 0.0001),
      or neuropathic pain (OR = 1.415, P < 0.02). In veterans age 36-45 years, those
      living in small rural areas had higher odds of chronic opioid use (OR = 1.31, P <
      0.0001, and OR = 1.33, P = 0.006, respectively) and back pain (OR = 1.36, P =
      0.003). Headache/migraine pain was associated with decreased odds of chronic
      opioid use (OR = 0.639, P = 0.003). Conclusions: Prevalence of opioid use is
      relatively low among OEF/OIF/OND veterans with newly diagnosed TBI who are using
      VHA. Among those who initiated opioids, about 25% use them chronically.
      Prescribing was mostly limited to moderate doses, with most veterans using
      opioids for approximately two months of the 12-month study period.

PMID- 29036681
TI  - Intra-specific trends of lumen and wall resistivities of vessels within the stem
      xylem vary among three woody plants.
AB  - Water flow through xylem vessels encounters hydraulic resistance when passing
      through the vessel lumen and end wall. Comparative studies have reported that
      lumen and end wall resistivities co-limit water flow through stem xylem in
      several angiosperm woody species that have vessels of different average diameter
      and length. This study examined the intra-specific relationship between the lumen
      and end wall resistivities (Rlumen and Rwall) for vessels within the stem xylem
      using three deciduous angiosperm woody species found in temperate forest. Morus
      australis Poir. and Acer rufinerve Siebold et Zucc. are early- and late
      successional species, and Vitis coignetiae Pulliat ex Planch is a woody liana.
      According to the Hagen-Poiseuille equation, Rlumen is proportional to the fourth
      power of vessel diameter (D), whereas vessel length (L) and inter-vessel pit area
      (Apit) determine Rwall. To estimate Rlumen and Rwall, the scaling relationships
      between the L and D and between Apit and D were measured. The scaling exponents
      between L and D were 1.47, 3.19 and 2.86 for A. rufinerve, M. australis and V.
      coignetiae, respectively, whereas those between Apit and D were 0.242, 2.11 and
      2.68, respectively. Unlike the inter-specific relationships, the wall resistivity
      fraction (Rwall/(Rlumen + Rwall)) within xylem changed depending on D. In M.
      australis and V. coignetiae, this fraction decreased with increasing D, while in
      A. rufinerve, it increased with D. Vessels with a high wall resistivity fraction
      have high Rwall and total resistivity but are expected to have low susceptibility
      to xylem cavitation due to a small cumulative Apit. In contrast, vessels with a
      low wall resistivity fraction have low Rwall and total resistivity but high
      susceptibility to xylem cavitation. Because the wall resistivity fraction varies
      with D, the stem xylem contains vessels with different hydraulic efficiencies and
      safety to xylem cavitation. These features produce differences in the hydraulic
      properties of plants with different life forms.

PMID- 29036682
TI  - Perinatal Risk Factors for Neonatal Early-onset Group B Streptococcal Sepsis
      after Initiation of Risk-based Maternal Intrapartum Antibiotic Prophylaxis-A Case
      Control Study.
AB  - Objectives: To identify the perinatal risk factors for early-onset Group B
      Streptococcus (EOGBS) sepsis in neonates after inception of a risk-based maternal
      intrapartum antibiotic prophylaxis strategy in 2004. Design: Case control study.
      Methods: All newborn with early onset GBS sepsis (born between 2004 and 2013)
      were deemed to be "cases" and controls were selected in a 1:4 ratio. Results:
      More than three per vaginal (PV) examinations [odds ratio (OR) 8.57, 95%
      confidence interval (CI) 3.10-23.6] was a significant risk factors. Peripartum
      fever (OR 3.54, 95% CI 1.3-9.67), urinary tract infection (OR 2.88, 95% CI 1.08
      7.63), meconium-stained amniotic fluid (MSAF) (OR 2.52, 95% CI 1.18-5.37) and
      caesarean section (OR 1.99, 95% CI 1.16-3.43) were also found to be associated
      with EOGBS sepsis. Conclusion: Multiple vaginal examinations are the strongest
      risk factors for peripartum Group B Streptococcal (GBS) sepsis. The association
      of MSAF and caesarean section indicates that foetal distress is an early symptom
      of perinatal GBS infection.

PMID- 29036683
TI  - CR2Cancer: a database for chromatin regulators in human cancer.
AB  - Chromatin regulators (CRs) can dynamically modulate chromatin architecture to
      epigenetically regulate gene expression in response to intrinsic and extrinsic
      signalling cues. Somatic alterations or misexpression of CRs might reprogram the
      epigenomic landscape of chromatin, which in turn lead to a wide range of common
      diseases, notably cancer. Here, we present CR2Cancer, a comprehensive annotation
      and visualization database for CRs in human cancer constructed by high throughput
      data analysis and literature mining. We collected and integrated genomic,
      transcriptomic, proteomic, clinical and functional information for over 400 CRs
      across multiple cancer types. We also built diverse types of CR-associated
      relations, including cancer type dependent (CR-target and miRNA-CR) and
      independent (protein-protein interaction and drug-target) ones. Furthermore, we
      manually curated around 6000 items of aberrant molecular alterations and
      interactions of CRs in cancer development from 5007 publications. CR2Cancer
      provides a user-friendly web interface to conveniently browse, search and
      download data of interest. We believe that this database would become a valuable
      resource for cancer epigenetics investigation and potential clinical application.
      CR2Cancer is freely available at http://cis.hku.hk/CR2Cancer.

PMID- 29036684
TI  - YEASTRACT: an upgraded database for the analysis of transcription regulatory
      networks in Saccharomyces cerevisiae.
AB  - The YEAst Search for Transcriptional Regulators And Consensus Tracking (YEASTRACT
      www.yeastract.com) information system has been, for 11 years, a key tool for the
      analysis and prediction of transcription regulatory associations at the gene and
      genomic levels in Saccharomyces cerevisiae. Since its last update in June 2017,
      YEASTRACT includes approximately 163000 regulatory associations between
      transcription factors (TF) and target genes in S. cerevisiae, based on more than
      1600 bibliographic references; it also includes 247 specific DNA binding
      consensus recognized by 113 TFs. This release of the YEASTRACT database provides
      new visualization tools to visualize each regulatory network in an interactive
      fashion, enabling the user to select and observe subsets of the network such as:
      (i) considering only DNA binding evidence or both DNA binding and expression
      evidence; (ii) considering only either positive or negative regulatory
      associations; or (iii) considering only one set of related environmental
      conditions. A further tool to observe TF regulons is also offered, enabling a
      clear-cut understanding of the exact meaning of the available data. We believe
      that with this new version, YEASTRACT will improve its role as an open web
      resource instrumental for Yeast Biologists and Systems Biology researchers.

PMID- 29036685
TI  - NUCLEAR HEATING IN LIF DOSEMETERS IN A FUSION NEUTRON FIELD, TRIAL OF DIRECT
      COMPARISON OF EXPERIMENTAL AND SIMULATED RESULTS.
AB  - The results of nuclear heating measured by means of thermoluminescent dosemeters
      (TLD-LiF) in a Cu block irradiated by 14 MeV neutrons are presented. The integral
      Cu experiment relevant for verification of copper nuclear data at neutron
      energies characteristic for fusion facilities was performed in the ENEA FNG
      Laboratory at Frascati. Five types of TLDs were used: highly photon sensitive
      LiF:Mg,Cu,P (MCP-N), 7LiF:Mg,Cu,P (MCP-7) and standard, lower sensitivity
      LiF:Mg,Ti (MTS-N), 7LiF:Mg,Ti (MTS-7) and 6LiF:Mg,Ti (MTS-6). Calibration of the
      detectors was performed with gamma rays in terms of air-kerma (10 mGy of 137Cs
      air-kerma). Nuclear heating in the Cu block was also calculated with the use of
      MCNP transport code Nuclear heating in Cu and air in TLD's positions was
      calculated as well. The nuclear heating contribution from all simulated by MCNP6
      code particles including protons, deuterons, alphas tritons and heavier ions
      produced by the neutron interactions were calculated. A trial of the direct
      comparison between experimental results and results of simulation was performed.

PMID- 29036686
TI  - COMPARISON OF APPROACHES TO OBTAIN A SAMPLE OF DWELLINGS FOR RADON SURVEY.
AB  - Obtaining of the representative sample of dwellings is a basic requirement to
      organization of the radon survey. Since random selection is often impossible,
      quasi-random approaches are used. The aim of the study is to analyze errors in
      radon exposure assessment that resulted from rejecting the random selection. Both
      the modeling and experiments were conducted. Three types of errors were observed:
      shifting of the mean, change of the variance and mixture of the previous two.

PMID- 29036689
TI  - HIGH DOSE FAST NEUTRON DOSIMETRY USING PADC PLASTIC NUCLEAR TRACK DETECTORS AND
      GREY LEVEL ANALYSIS.
AB  - The objective of this work is to demonstrate the possibility of performing fast
      neutron dosimetry up to 5 Sv using optical absorbance of polyallyl diglycol
      carbonate (PADC) detectors, obtained through grey level analysis of PADC images
      acquired with a commercial track-counting dosimetry system, and estimate the
      uncertainties involved. PADCs were irradiated with doses from 100 mSv to 5 Sv
      (252Cf source) and etched. PADC images were acquired using the TASLIMAGETM
      Neutron Dosimetry System (Track Analysis Systems Ltd.) and analysed to obtain the
      grey levels and the optical absorbance. The absorbance from different detectors
      and batches was analysed to determine the uncertainties involved, from which the
      final uncertainty in the method, ~30% and dominated by the uncertainty in the
      calibration curve, was estimated. A dose estimation <2 Sv can also be performed
      using a 'universal curve' by normalising the absorbance to that of a detector
      irradiated with 1 Sv. The data presented here allows the extension of the dose
      range of track counting systems using no additional equipment, only the images
      already acquired by the systems.

PMID- 29036688
TI  - A cell-penetrating antibody inhibits human RAD51 via direct binding.
AB  - RAD51, a key factor in homology-directed repair (HDR), has long been considered
      an attractive target for cancer therapy, but few specific inhibitors have been
      found. A cell-penetrating, anti-DNA, lupus autoantibody, 3E10, was previously
      shown to inhibit HDR, sensitize tumors to radiation, and mediate synthetic lethal
      killing of BRCA2-deficient cancer cells, effects that were initially attributed
      to its affinity for DNA. However, as the molecular basis for its ability to
      inhibit DNA repair, we report that 3E10 directly binds to the N-terminus of
      RAD51, sequesters RAD51 in the cytoplasm, and impedes RAD51 binding to DNA.
      Further, we generate separation-of-function mutations in the complementarity
      determining regions of 3E10 revealing that inhibition of HDR tracks with binding
      to RAD51 but not to DNA, whereas cell penetration is linked to DNA binding. The
      consequences of these mutations on putative 3E10 interactions with RAD51 and DNA
      are correlated with in silico molecular modeling. Taken together, the results
      identify 3E10 as a novel inhibitor of RAD51 by direct binding, accounting for its
      ability to suppress HDR and providing the molecular basis to guide pre-clinical
      development of 3E10 as an anti-cancer agent.

PMID- 29036687
TI  - Measuring deaminated nucleotide surveillance enzyme ITPA activity with an ATP
      releasing nucleotide chimera.
AB  - Nucleotide quality surveillance enzymes play important roles in human health, by
      detecting damaged molecules in the nucleotide pool and deactivating them before
      they are incorporated into chromosomal DNA or adversely affect metabolism. In
      particular, deamination of adenine moiety in (deoxy)nucleoside triphosphates,
      resulting in formation of (d)ITP, can be deleterious, leading to DNA damage,
      mutagenesis and other harmful cellular effects. The 21.5 kDa human enzyme that
      mitigates this damage by conversion of (d)ITP to monophosphate, ITPA, has been
      proposed as a possible therapeutic and diagnostic target for multiple diseases.
      Measuring the activity of this enzyme is useful both in basic research and in
      clinical applications involving this pathway, but current methods are
      nonselective and are not applicable to measurement of the enzyme from cells or
      tissues. Here, we describe the design and synthesis of an ITPA-specific chimeric
      dinucleotide (DIAL) that replaces the pyrophosphate leaving group of the native
      substrate with adenosine triphosphate, enabling sensitive detection via
      luciferase luminescence signaling. The probe is shown to function sensitively and
      selectively to quantify enzyme activity in vitro, and can be used to measure the
      activity of ITPA in bacterial, yeast and human cell lysates.

PMID- 29036690
TI  - Simultaneous Measurements of Nanoaerosols and Radioactive Aerosols Containing the
      Short-lived Radon Isotopes.
AB  - The activity size distribution of the Equilibrium-Equivalent Concentration (EER)
      of 222Rn is one of the most important parameters for the estimation of radiation
      dose by inhalation of radon decay products. A series of measurements of the EER
      activity size distribution were performed by the screen diffusion battery in
      Radon-Aerosol chamber (10 m3) at the National Institute for Nuclear, Chemical,
      and Biological Protection (SUJCHBO). These measurements were performed at
      different levels of radon concentration. For this study, the Graded Screen Array
      Diffusion Battery (GSA DB), developed by the SUJCHBO (based on Earl Knutson and
      Robert F Holub design), consists of 10 screens and backup filter used to collect
      all particles that penetrated the screens. The measuring range of this GSA DB
      allows measuring the radioactive nanoaerosols in the size range from 0.5 to 100
      nm. The Earl Knutson algorithm was used for EER activity size distribution
      evaluation. The results of EER activity size distribution were subsequently
      compared with the aerosol particle size distribution measured by Scanning
      Mobility Particle Sizer Spectrometer (SMPS 3936 N, TSI Inc., MN, USA).

PMID- 29036692
TI  - Clinical utility of texture analysis of 18F-FDG PET/CT in patients with Stage I
      lung cancer treated with stereotactic body radiotherapy.
AB  - We evaluated the reproducibility and predictive value of texture parameters and
      existing parameters of 18F-FDG PET/CT images in Stage I non-small-cell lung
      cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT).
      Twenty-six patients with Stage I NSCLC (T1-2N0M0) were retrospectively analyzed.
      All of the patients underwent an 18F-FDG PET/CT scan before treatment and were
      treated with SBRT. Each tumor was delineated using PET Edge (MIM Software Inc.,
      Cleveland, OH), and texture parameters were calculated using open-source code
      CGITA. From 18F-FDG PET/CT images, three conventional parameters, including
      maximum standardized uptake value (SUV), metabolic tumor volume (MTV) and total
      lesion glycolysis (TLG), and four texture parameters, including entropy and
      dissimilarity (derived from a co-occurrence matrix) and high-intensity large-area
      emphasis (HILAE) and zone percentage (derived from a size-zone matrix) were
      analyzed. Reproducibility was evaluated using two independent delineations
      conducted by two observers. The ability to predict local control (LC),
      progression-free survival (PFS) and overall survival (OS) was tested for each
      parameter. All of the seven parameters except zone percentage showed good
      reproducibility, with intraclass correlation coefficient values >0.8. In
      univariate analysis, only HILAE was a significant predictor for LC. Histology,
      dose fractionation, and maximum SUV were associated with PFS, and histology and
      dose fractionation were associated with OS. We showed that texture parameters
      derived from 18F-FDG PET/CT were reproducible and potentially beneficial for
      predicting LC in Stage I lung cancer patients treated with SBRT.

PMID- 29036691
TI  - Nuclear localized C9orf72-associated arginine-containing dipeptides exhibit age
      dependent toxicity in C. elegans.
AB  - A hexanucleotide repeat expansion mutation in the C9orf72 gene represents a
      prevalent genetic cause of several neurodegenerative diseases, including
      amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Non-canonical
      translation of this repeat gives rise to several distinct dipeptide protein
      species that could play pathological roles in disease. Here, we show in the model
      system Caenorhabditis elegans that expression of the arginine-containing
      dipeptides, but not alanine-containing dipeptides, produces toxic phenotypes in
      multiple cellular contexts, including motor neurons. Expression of either (PR)50
      or (GR)50 during development caused a highly penetrant developmental arrest,
      while post-developmental expression caused age-onset paralysis. Both (PR)50- and
      (GR)50-green fluorescent protein tagged dipeptides were present in the nucleus
      and nuclear localization was necessary and sufficient for their toxicity. Using
      an inducible expression system, we discovered that age-onset phenotypes caused by
      (PR)50 required both continual (PR)50 expression and an aged cellular
      environment. The toxicity of (PR)50 was modified by genetic mutations that
      uncouple physiological aging from chronological aging. However, these same
      mutations failed to modify the toxicity of (GR)50, suggesting that (PR)50 and
      (GR)50 exert their toxicity through partially distinct mechanism(s). Changing the
      rate of physiological aging also mitigates toxicity in other C. elegans models of
      ALS, suggesting that the (PR)50 dipeptide might engage similar toxicity
      mechanisms as other ALS disease-causing proteins.

PMID- 29036693
TI  - ICG: a wiki-driven knowledgebase of internal control genes for RT-qPCR
      normalization.
AB  - Real-time quantitative PCR (RT-qPCR) has become a widely used method for accurate
      expression profiling of targeted mRNA and ncRNA. Selection of appropriate
      internal control genes for RT-qPCR normalization is an elementary prerequisite
      for reliable expression measurement. Here, we present ICG (http://icg.big.ac.cn),
      a wiki-driven knowledgebase for community curation of experimentally validated
      internal control genes as well as their associated experimental conditions.
      Unlike extant related databases that focus on qPCR primers in model organisms
      (mainly human and mouse), ICG features harnessing collective intelligence in
      community integration of internal control genes for a variety of species.
      Specifically, it integrates a comprehensive collection of more than 750 internal
      control genes for 73 animals, 115 plants, 12 fungi and 9 bacteria, and
      incorporates detailed information on recommended application scenarios
      corresponding to specific experimental conditions, which, collectively, are of
      great help for researchers to adopt appropriate internal control genes for their
      own experiments. Taken together, ICG serves as a publicly editable and open
      content encyclopaedia of internal control genes and accordingly bears broad
      utility for reliable RT-qPCR normalization and gene expression characterization
      in both model and non-model organisms.

PMID- 29036694
TI  - Efficient modulation of photosynthetic apparatus confers desiccation tolerance in
      the resurrection plant Boea hygrometrica.
AB  - Boea hygrometrica (B. hygrometrica) can tolerate severe desiccation and resume
      photosynthetic activity rapidly upon water availability. However, little is known
      about the mechanisms by which B. hygrometrica adapts to dehydration and resumes
      competence upon rehydration. Here we determine how B. hygrometrica deals with
      oxidative stress, excessive excitation/electron pressures as well as
      photosynthetic apparatus modulation during dehydration/rehydration. By measuring
      ROS generation and scavenging efficiency, we found that B. hygrometrica possesses
      efficient strategies to maintain cellular redox homeostasis. Transmission
      electron microscopy (TEM) analysis revealed a remarkable alteration of
      chloroplast architecture and plastoglobules (PGs) accumulation during
      dehydration/rehydration. Pulse-amplitude modulated (PAM) chlorophyll fluorescence
      measurements, P700 redox assay as well as chlorophyll fluorescence emission
      spectra analysis on leaves of B. hygrometrica during dehydration/rehydration were
      also performed. Results showed that the photochemical activity of PSII as well as
      photoprotective energy dissipation in PSII undergo gradual
      inactivation/activation during dehydration/rehydration in B. hygrometrica; PSI
      activity is relatively induced upon water deficit, and dehydration leads to
      physical interaction between PSI and LHCII. Furthermore, blue-native
      polyacrylamide gel electrophoresis (BN-PAGE) and immunoblot analysis revealed
      that the protein abundance of light harvesting complexes decrease markedly along
      with internal water deficit to restrict light absorption and attenuate electron
      transfer, resulting in limited light excitation and repressed photosynthesis. In
      contrast, many thylakoid proteins remain at a basal level even after full
      dehydration. Taken together, our study demonstrated that efficient modulation of
      cellular redox homeostasis and photosynthetic activity confers desiccation
      tolerance in B. hygrometrica.

PMID- 29036695
TI  - Identifying Greener and Safer Plasticizers: A 4-Step Approach.
AB  - The health and economic burden of endocrine disrupting chemicals, such as the
      plasticizer di(2-ethylhexyl) phthalate (DEHP), is prompting industry to develop
      alternatives. However, the absence of requirements for manufacturers to ensure
      the safety of these alternatives has led to the generation of replacements that
      may have similar or worse effects than the original chemicals. Consequently,
      there is increasing recognition by scientists, regulators and industry that
      proactive approaches are needed to develop safe chemical substitutes. We propose
      a 4-step approach for the design, characterization and toxicological testing of
      responsible alternative chemicals that we illustrate with our ongoing studies on
      DEHP replacements. Our approach is comprised of: (1) the design and
      characterization of alternative chemicals based on innovative chemical structures
      and environmental considerations; (2) large-scale in vitro cell-based high
      throughput and selective ex vivo studies to preselect the most innocuous
      alternatives; (3) an acute toxicity in vivo study to rule out overt toxicity of
      the selected candidates; and (4) an in utero and lactational exposure study
      comparing the effects of selected candidates to those currently in use,
      emphasizing commonly described phenotypes after exposure to the latter. Using
      this 4-step approach, we have identified 2 alternative chemicals displaying good
      plasticizing properties, better biodegradability, and less leaching than DEHP
      without any apparent toxicity in vivo. This process has thus far proven useful in
      the proactive identification of responsible chemical replacements for DEHP.

PMID- 29036696
TI  - RADIATION PROTECTION MEASUREMENTS WITH THE VARIANCE-COVARIANCE METHOD IN THE
      STRAY RADIATION FIELDS FROM PHOTON AND PROTON THERAPY FACILITIES.
AB  - The microdosimetric variance-covariance method was used to study the stray
      radiation fields from the photon therapy facility at the Technical University of
      Denmark and the scanned proton therapy beam at the Skandion Clinic in Uppsala,
      Sweden. Two TEPCs were used to determine the absorbed dose, the dose-average
      lineal energy, the dose-average quality factor and the dose equivalent. The
      neutron component measured by the detectors at the proton beam was studied
      through Monte Carlo simulations using the code MCNP6. In the photon beam the
      stray absorbed dose ranged between 0.3 and 2.4 MUGy per monitor unit, and the
      dose equivalent between 0.4 and 9 MUSv per monitor unit, depending on beam energy
      and measurement position. In the proton beam the stray absorbed dose ranged
      between 3 and 135 MUGy per prescribed Gy, depending on detector position and
      primary proton energy.

PMID- 29036697
TI  - The elderly left behind-changes in survival trends of primary central nervous
      system lymphoma over the past 4 decades.
AB  - Background: There has been significant improvement in treatment outcomes of
      primary central nervous system lymphoma (PCNSL) at specialized centers over the
      past several decades; however, it is unclear if these changes have translated to
      benefits in the general population. Methods: In this study, we utilized 2
      national databases to examine survival trends over time for PCNSL: the Central
      Brain Tumor Registry of the United States (CBTRUS, 2000-2013) and 18 registries
      from the Surveillance, Epidemiology, and End Results program (SEER, 1973-2013).
      Results: The annual incidence of PCNSL in 2013 was 0.4 per 100000 population
      (CBTRUS/SEER). Incidence increased from 0.1 per 100000 in the 1970s to 0.4 per
      100000 in the 1980s, correlating with an increase in the diagnosis of patients
      >=70 years (1973: 0.2 vs 2013: 2.1 [SEER]). Incidence rates differed greatly
      between young and elderly patients (age 20-29 y: 0.08 vs 70-79 y: 4.32 [CBTRUS]).
      Even though the median overall survival of all patients doubled from 12.5 months
      in the 1970s to 26 months in the 2010s, this survival benefit was limited to
      patients <70 years. Survival in the elderly population has not changed in the
      last 40 years (6 mo in the 1970s vs 7 mo in the 2010s, P = 0.1). Conclusion: The
      poor outcome seen in the particularly vulnerable elderly patient population
      highlights the need for clinical trials targeting the elderly in hopes of
      improving treatment strategies and survival.

PMID- 29036698
TI  - Chromosomal Context Affects the Molecular Evolution of Sex-linked Genes and Their
      Autosomal Counterparts in Turtles and Other Vertebrates.
AB  - Sex chromosomes evolve differently from autosomes because natural selection acts
      distinctly on them given their reduced recombination and smaller population size.
      Various studies of sex-linked genes compared with different autosomal genes
      within species support these predictions. Here, we take a novel alternative
      approach by comparing the rate of evolution between subsets of genes that are sex
      linked in selected reptiles/vertebrates and the same genes located in autosomes
      in other amniotes. We report for the first time the faster evolution of Z-linked
      genes in a turtle (the Chinese softshell turtle Pelodiscus sinensis) relative to
      autosomal orthologs in other taxa, including turtles with temperature-dependent
      sex determination (TSD). This faster rate was absent in its close relative, the
      spiny softshell turtle (Apalone spinifera), thus revealing important lineage
      effects, and was only surpassed by mammalian-X linked genes. In contrast, we
      found slower evolution of X-linked genes in the musk turtle Staurotypus
      triporcatus (XX/XY) and homologous Z-linked chicken genes. TSD lineages displayed
      overall faster sequence evolution than taxa with genotypic sex determination
      (GSD), ruling out global effects of GSD on molecular evolution beyond those by
      sex-linkage. Notably, results revealed a putative selective sweep around two
      turtle genes involved in vertebrate gonadogenesis (Pelodiscus-Z-linked Nf2 and
      Chrysemys-autosomal Tspan7). Our observations reveal important evolutionary
      changes at the gene level mediated by chromosomal context in turtles despite
      their low overall evolutionary rate and illuminate sex chromosome evolution by
      empirically testing expectations from theoretical models. Genome-wide analyses
      are warranted to test the generality and prevalence of the observed patterns.

PMID- 29036699
TI  - Pain-Related Acceptance as a Mediator in the Fear Avoidance Model of Chronic
      Pain: A Preliminary Study.
AB  - Objective: The fear avoidance model has served as a popular, heuristic model in
      explaining the transition from acute to chronic pain. In addition, the
      significance of pain-related acceptance in chronic pain development and
      adjustment is underlined in a vast number of empirical studies. The objective of
      the current preliminary study was to investigate pain-related acceptance as a
      mediator within the key cognitive relationships proposed by the fear avoidance
      model of chronic pain. Materials and Methods. In a cross-sectional design, bodily
      pain, pain catastrophizing, fear avoidance beliefs, and pain-related acceptance
      were assessed by questionnaires in 125 chronic pain patients in a Danish
      multidisciplinary pain center. Mediation analyses were performed to test the
      effect of pain-related acceptance on bodily pain, pain catastrophizing, and fear
      avoidance beliefs. Results: Medium-sized correlations were found between all
      outcomes. Mediation analyses revealed that pain-related acceptance was a
      significant mediator between 1) bodily pain and pain catastrophizing and 2) pain
      catastrophizing and fear avoidance beliefs after controlling for bodily pain.
      Furthermore, pain-related acceptance accounted for a large proportion in both
      associations (82.2% and 56.1%). Conclusions: The results suggest that pain
      related acceptance is a prominent psychological mechanism within the key
      cognitive associations of the fear avoidance model, which predicts a certain path
      of cognitive, emotional, and behavioral factors in the development and
      maintenance of chronic pain. This proposes pain-related acceptance to be an
      important mechanism that possibly counteracts the negative reactions of pain
      catastrophizing and fear avoidance beliefs. These findings should be investigated
      further and could potentially be an important place to intervene clinically in
      order to counteract the development and/or maintenance of chronic pain.

PMID- 29036700
TI  - EXPERIMENTAL EVALUATION OF NEUTRON SHIELDING MATERIALS.
AB  - A new proposed design of neutron shielding material-based on the commercial
      material Borotron UH050 with an addition of Al(OH)3-is evaluated in order to
      determine if its neutron and gamma shielding properties match those of a
      reference material, NS4FR. Neutron and gamma dosimetry measurements are
      performed, as well as neutron spectrometry measurements and Monte Carlo
      simulations. Negligible differences are found between the materials for neutron
      shielding, while significant differences are found for gamma shielding. The
      effect of Al(OH)3 addition to Borotron UH050 is to reduce neutron shielding
      properties while increasing gamma shielding properties. The resulting material is
      as efficient as NS4FR for neutron shielding but less efficient for gamma
      shielding-thicknesses 20% higher are required to match gamma shielding properties
      of NS4FR. Monte Carlo models of the materials are validated based on the
      performed measurements of neutron spectra and neutron and gamma ambient dose
      equivalent.

PMID- 29036703
TI  - Spiritual/Religious Distress Is Associated with Pain Catastrophizing and
      Interference in Veterans with Chronic Pain.
AB  - Objective: Few studies have examined relations between one important aspect of
      spiritual/religious functioning-spiritual distress-and pain-related outcomes, and
      none has examined how spiritual distress and depression conjointly relate to
      chronic pain. The goal of the present study, then, was to examine veterans'
      spiritual distress as a predictor of two aspects of chronic pain, catastrophizing
      and interference, testing a mediational model of depression. Design: Four hundred
      thirty-six patients seeking treatment in a chronic pain management clinic
      responded to a mailed survey assessing demographics, spiritual distress,
      depression, pain catastrophizing, and pain interference. Setting: Participants
      were drawn from a list of patients enrolled in a chronic pain rehabilitation
      program at a large Midwestern Veterans Affairs health care system. Subjects:
      Participants were 436 veterans seeking chronic pain rehabilitation. The sample
      was predominantly Caucasian and male. Methods: Survey data were subjected to
      mediational analysis, assessing both direct effects of spiritual distress on pain
      outcomes and indirect effects of spiritual distress through depression. Results:
      Results showed that spiritual distress was moderately strongly related to both
      pain outcomes. Further, depression mediated links between spiritual distress and
      pain catastrophizing (partially) and interference (fully). Conclusions: These
      results have implications for further research in spiritually integrated care as
      a component of holistic, integrative approaches to the management of chronic
      pain.

PMID- 29036701
TI  - Mismatch Negativity But Not P300 Is Associated With Functional Disability in
      Schizophrenia.
AB  - Mismatch negativity (MMN) and P300 event-related potential (ERP) reductions in
      schizophrenia (SZ) reflect preattentive and attention-mediated auditory
      processing deficits, respectively. Although both have been linked to cognitive
      deficits in SZ, their relative contributions to real-world functioning are
      unclear. We sought to determine the functional significance of disrupted auditory
      processing in SZ by examining MMN and P300 in typically disabled low-functioning
      patients and in patients with high levels of independent role functioning. MMN to
      auditory deviants and P300 to infrequent auditory target and nontarget novel
      stimuli were assessed in 20 high-functioning SZ patients (HF-SZ), 17 low
      functioning patients (LF-SZ), and 35 healthy comparison (HC) subjects. There was
      a group effect on MMN and P300 amplitudes across stimulus types. MMN was
      significantly diminished in LF-SZ compared to HF-SZ and HC, and HF-SZ
      demonstrated comparable MMN to HC. In contrast, P300 was significantly reduced in
      both LF-SZ and HF-SZ compared to HC. Logistic regression suggested independent
      sensitivity of MMN to functioning in SZ over and above P300 measures. Neither MMN
      nor P300 were associated with positive or negative symptom severity. Results
      replicate MMN and P300 abnormalities in SZ, and also suggest that the neural
      mechanisms associated with the preattentive detection of auditory deviance are
      most compromised in patients with functional disability. MMN may index
      pathophysiological processes that are critical for optimal functioning in SZ.

PMID- 29036702
TI  - A hyperdynamic H3.3 nucleosome marks promoter regions in pluripotent embryonic
      stem cells.
AB  - Histone variants and their chaperones are key regulators of eukaryotic
      transcription, and are critical for normal development. The histone variant H3.3
      has been shown to play important roles in pluripotency and differentiation, and
      although its genome-wide patterns have been investigated, little is known about
      the role of its dynamic turnover in transcriptional regulation. To elucidate the
      role of H3.3 dynamics in embryonic stem cell (ESC) biology, we generated mouse
      ESC lines carrying a single copy of a doxycycline (Dox)-inducible HA-tagged
      version of H3.3 and monitored the rate of H3.3 incorporation by ChIP-seq at
      varying time points following Dox induction, before and after RA-induced
      differentiation. Comparing H3.3 turnover profiles in ESCs and RA-treated cells,
      we identified a hyperdynamic H3.3-containing nucleosome at the -1 position in
      promoters of genes expressed in ESCs. This dynamic nucleosome is restricted and
      shifted downstream into the +1 position following differentiation. We suggest
      that histone turnover dynamics provides an additional mechanism involved in
      expression regulation, and that a hyperdynamic -1 nucleosome marks promoters in
      ESCs. Our data provide evidence for regional regulation of H3.3 turnover in ESC
      promoters, and calls for testing, in high resolution, the dynamic behavior of
      additional histone variants and other structural chromatin proteins.

PMID- 29036704
TI  - MEASUREMENTS OF AIRBORNE CONCENTRATIONS OF RADON AND THORON DECAY PRODUCTS.
AB  - Liquid scintillation counting (LSC) is a measuring technique, broadly applied in
      environmental monitoring of radionuclides. One of the possible applications of
      LSC is the measurement of radon and thoron decay products. But this method is
      suitable only for grab sampling. For long-term measurements a different technique
      can be applied-monitors of potential alpha energy concentration (PAEC) with
      thermoluminescent detectors (TLD). In these devices, called Alfa-2000 sampling
      probe, TL detectors (CaSO4:Dy) are applied for alpha particles counting. Three
      independent heads are placed over the membrane filter in a dust sampler's
      microcyclone. Such solution enables simultaneous measurements of PAEC and dust
      content. Moreover, the information which is stored in TLD chips is the energy of
      alpha particles, not the number of counted particles. Therefore, the readout of
      TL detector shows directly potential alpha energy, with no dependence on
      equilibrium factor, etc. This technique, which had been used only for radon decay
      products measurements, was modified by author to allow simultaneous measurements
      of radon and thoron PAEC. The LSC method can be used for calibration of portable
      radon decay products monitors. The LSC method has the advantage to be an absolute
      one, the TLD method to measure directly the (dose relevant) deposited energy.

PMID- 29036706
TI  - Faucial diphtheria.

PMID- 29036705
TI  - Chalcogenozidovudine Derivatives With Antitumor Activity: Comparative Toxicities
      in Cultured Human Mononuclear Cells.
AB  - Considering a novel series of zidovudine (AZT) derivatives encompassing
      selenoaryl moieties promising candidates as therapeutics, we examined the
      toxicities elicited by AZT and derivatives 5'-(4-Chlorophenylseleno)zidovudine
      (SZ1); 5'-(Phenylseleno)zidovudine (SZ2); and 5'-(4-Methylphenylseleno)zidovudine
      (SZ3) in healthy cells and in mice. Resting and stimulated cultured human
      peripheral blood mononuclear cells (PBMCs) were treated with the compounds at
      concentrations ranging from 10 to 200 uM for 24 and/or 72 h. Adult mice received
      a single injection of compounds (100 umol/kg, s.c.) and 72 h after
      administration, hepatic/renal biomarkers were analyzed. Resting and stimulated
      PBMCs exposed to SZ1 displayed loss of viability, increased reactive species
      production, disruption in cell cycle, apoptosis and increased transcript levels
      and production of pro-inflammatory cytokines. In a mild way, most of these
      effects were also induced by SZ2. AZT and SZ3 did not cause significant toxicity
      towards resting PBMCs. Differently, both compounds elicited apoptosis and S phase
      arrest in stimulated cells. AZT and derivatives administration did not change the
      body weight and plasma biochemical markers in mice. However, the absolute weight
      and organ-to-body weight ratio of liver, kidneys and spleen were altered in AZT,
      SZ1-, and SZ2-treated mice. Our results highlighted the involvement of
      derivatives SZ1 and SZ2 in redox and immunological dyshomeostasis leading to
      activation of apoptotic signaling pathways in healthy cells under different
      division phases. On the other hand, the derivative SZ3 emerged as a promising
      candidate for further viral infection/antitumor studies as a new effective
      therapy with low toxicity for immune cells and after acute in vivo treatment.

PMID- 29036707
TI  - INTRODUCTION AND TESTING OF A SIMPLIFIED METHOD FOR THE EVALUATION OF THE RADON
      EMANATION.
AB  - The radioactive noble gas radon is identified as the highest risk factor for lung
      cancer after smoking. The exhalation of radon from building materials can
      contribute to the radon indoor activity concentration. Therefore, the emanation
      of radon might be a crucial factor. It is defined as the release of radon from
      the solid soil matter into the pore space of the material. This article describes
      a new on-site measurement method for the emanation of radon from building
      materials at industrial sites. Therefore, a closed vessel with sample material
      and a passive radon detector inside is used to measure the integrated build-up
      curve of the activity concentration. Additionally, a brief overview on existing
      radon emanation measurement methods is given.

PMID- 29036708
TI  - RADON MEASUREMENTS IN KINDERGARTENS IN URAL REGION (RUSSIA).
AB  - The radon survey of kindergartens has been conducted in Sverdlovskaya oblast
      during 2013-16. Indoor radon concentrations have been measured in 180
      kindergartens in 21 villages and 10 towns. The LR-115 nuclear track detectors
      were placed in 560 rooms (three or four rooms per kindergarten) during 2-3
      months. To obtain annual values, radon measurements were carried in the cold and
      warm seasons. The arithmetic and geometric means of annual indoor radon
      concentrations in rooms are 59 and 42 Bq/m3 respectively, GSD = 2.33. Analysis of
      the building factors affecting radon entry is presented. The detailed radon
      survey was performed in one kindergarten where exceeding of national action radon
      level was observed.

PMID- 29036709
TI  - Deep learning of the splicing (epi)genetic code reveals a novel candidate
      mechanism linking histone modifications to ESC fate decision.
AB  - Alternative splicing (AS) is a genetically and epigenetically regulated pre-mRNA
      processing to increase transcriptome and proteome diversity. Comprehensively
      decoding these regulatory mechanisms holds promise in getting deeper insights
      into a variety of biological contexts involving in AS, such as development and
      diseases. We assembled splicing (epi)genetic code, DeepCode, for human embryonic
      stem cell (hESC) differentiation by integrating heterogeneous features of genomic
      sequences, 16 histone modifications with a multi-label deep neural network. With
      the advantages of epigenetic features, DeepCode significantly improves the
      performance in predicting the splicing patterns and their changes during hESC
      differentiation. Meanwhile, DeepCode reveals the superiority of epigenomic
      features and their dominant roles in decoding AS patterns, highlighting the
      necessity of including the epigenetic properties when assembling a more
      comprehensive splicing code. Moreover, DeepCode allows the robust predictions
      across cell lineages and datasets. Especially, we identified a putative H3K36me3
      regulated AS event leading to a nonsense-mediated mRNA decay of BARD1. Reduced
      BARD1 expression results in the attenuation of ATM/ATR signalling activities and
      further the hESC differentiation. These results suggest a novel candidate
      mechanism linking histone modifications to hESC fate decision. In addition, when
      trained in different contexts, DeepCode can be expanded to a variety of
      biological and biomedical fields.

PMID- 29036710
TI  - A disulfide bond A-like oxidoreductase is a strong candidate gene for self
      incompatibility in apricot (Prunus armeniaca) pollen.
AB  - S-RNase based gametophytic self-incompatibility (SI) is a widespread prezygotic
      reproductive barrier in flowering plants. In the Solanaceae, Plantaginaceae and
      Rosaceae gametophytic SI is controlled by the pistil-specific S-RNases and the
      pollen S-locus F-box proteins but non-S-specific factors, namely modifiers, are
      also required. In apricot, Prunus armeniaca (Rosaceae), we previously mapped two
      pollen-part mutations that confer self-compatibility in cultivars Canino and Katy
      at the distal end of chromosome 3 (M-locus) unlinked to the S-locus. Here, we
      used high-resolution mapping to identify the M-locus with an ~134 kb segment
      containing ParM-1-16 genes. Gene expression analysis identified four genes
      preferentially expressed in anthers as modifier gene candidates, ParM-6, -7, -9
      and -14. Variant calling of WGS Illumina data from Canino, Katy, and 10 self
      incompatible cultivars detected a 358 bp miniature inverted-repeat transposable
      element (MITE) insertion in ParM-7 shared only by self-compatible apricots,
      supporting ParM-7 as strong candidate gene required for SI. ParM-7 encodes a
      disulfide bond A-like oxidoreductase protein, which we named ParMDO. The MITE
      insertion truncates the ParMDO ORF and produces a loss of SI function, suggesting
      that pollen rejection in Prunus is dependent on redox regulation. Based on
      phylogentic analyses we also suggest that ParMDO may have originated from a
      tandem duplication followed by subfunctionalization and pollen-specific
      expression.

PMID- 29036711
TI  - Impacts of Electroconvulsive Therapy on 1-Year Outcomes in Patients With
      Schizophrenia: A Controlled, Population-Based Mirror-Image Study.
AB  - Objectives: Despite the decline in the use of electroconvulsive therapy (ECT) in
      patients with schizophrenia, ECT augmentation is still recommended for those with
      poor response to standard pharmacological intervention. However, the
      effectiveness of augmentation of antipsychotics with ECT on long-term clinical
      outcomes needs to be verified in an expanded sample. Methods: Patients who were
      hospitalized for schizophrenia and received ECT for the first time during that
      hospitalization were identified from the total population health insurance
      database in Taiwan between 2002 and 2011. A comparison group was randomly
      selected and matched by age, gender, calendar year of hospitalization, and
      duration of hospitalization. Using a mirror-image design, the changes in rates of
      psychiatric and overall hospitalization, length of hospital stay, number of
      emergency department visits, and direct medical costs across the 1-year pre- and
      post-treatment periods were examined. Results: A total of 2074 patients with the
      same number of comparison participants were included in the analysis. The rate of
      re-hospitalization decreased significantly in the ECT group during the 1-year
      post-treatment period, while there was no significant difference in the
      comparison group. Correspondingly, the total medical expenses increased
      significantly in the non-ECT group, but not in the ECT group. Notably, the
      reduction in the psychiatric re-hospitalization rate in the ECT group was more
      pronounced among those treated with clozapine or a medium-high average daily dose
      of antipsychotics. Conclusion: This 1-year mirror-image analysis indicated that
      augmentation of antipsychotics with ECT in schizophrenic patients was associated
      with a reduced rate of psychiatric re-hospitalization.

PMID- 29036712
TI  - COMPARISON OF COSMIC-RAY ENVIRONMENTS ON EARTH, MOON, MARS AND IN SPACECRAFT
      USING PHITS.
AB  - Estimation of cosmic-ray doses is of great importance not only in aircrew and
      astronaut dosimetry but also in evaluation of background radiation exposure to
      public. We therefore calculated the cosmic-ray doses on Earth, Moon and Mars as
      well as inside spacecraft, using Particle and Heavy Ion Transport code System
      PHITS. The same cosmic-ray models and dose conversion coefficients were employed
      in the calculation to properly compare between the simulation results for
      different environments. It is quantitatively confirmed that the thickness of
      physical shielding including the atmosphere and soil of the planets is the most
      important parameter to determine the cosmic-ray doses and their dominant
      contributors. The comparison also suggests that higher solar activity
      significantly reduces the astronaut doses particularly for the interplanetary
      missions. The information obtained from this study is useful in the designs of
      the future space missions as well as accelerator-based experiments dedicated to
      cosmic-ray research.

PMID- 29036713
TI  - REVISION OF ISO 8529-REFERENCE NEUTRON RADIATIONS.
AB  - ISO Standard 8529, on Reference neutron radiations, is due for revision. This
      paper covers proposed changes to Part 1 which dates from 2001. The changes are
      mainly designed to improve the data on radionuclide source neutron spectra, but
      also include options for modifying the content, e.g. the section on reactor
      filtered beams.

PMID- 29036714
TI  - Accounting for technical noise in differential expression analysis of single-cell
      RNA sequencing data.
AB  - Recent technological breakthroughs have made it possible to measure RNA
      expression at the single-cell level, thus paving the way for exploring expression
      heterogeneity among individual cells. Current single-cell RNA sequencing (scRNA
      seq) protocols are complex and introduce technical biases that vary across cells,
      which can bias downstream analysis without proper adjustment. To account for cell
      to-cell technical differences, we propose a statistical framework, TASC (Toolkit
      for Analysis of Single Cell RNA-seq), an empirical Bayes approach to reliably
      model the cell-specific dropout rates and amplification bias by use of external
      RNA spike-ins. TASC incorporates the technical parameters, which reflect cell-to
      cell batch effects, into a hierarchical mixture model to estimate the biological
      variance of a gene and detect differentially expressed genes. More importantly,
      TASC is able to adjust for covariates to further eliminate confounding that may
      originate from cell size and cell cycle differences. In simulation and real scRNA
      seq data, TASC achieves accurate Type I error control and displays competitive
      sensitivity and improved robustness to batch effects in differential expression
      analysis, compared to existing methods. TASC is programmed to be computationally
      efficient, taking advantage of multi-threaded parallelization. We believe that
      TASC will provide a robust platform for researchers to leverage the power of
      scRNA-seq.

PMID- 29036715
TI  - CERN IRRADIATION FACILITIES.
AB  - CERN provides unique irradiation facilities for applications in dosimetry,
      metrology, intercomparison of radiation protection devices, benchmark of Monte
      Carlo codes and radiation damage studies to electronics.

PMID- 29036716
TI  - Reconsidering 'Set the People Free': Neoliberalism and Freedom Rhetoric in
      Churchill's Conservative Party.
AB  - It is often assumed that 'Hayekian' or 'neoliberal' influences lay behind
      Conservative attacks on socialism in 1945 and subsequent calls to 'set the people
      free' in 1950 and 1951. This assumption has had consequences for our
      understanding of late-1940s Conservatism and for wider interpretations of post
      war politics. Heeding recent calls to reconnect the inter-war and post-war
      parties and to pay closer attention to how opponents and contexts generate
      arguments, this article revisits senior Conservatives' rhetoric between 1945 and
      1951 to break the link between neoliberal influence and freedom rhetoric. First,
      it argues that the rhetoric of 1945 was derived from a distinctly Conservative
      lineage of interwar argument and reflected strategies developed before the
      publication of F. A. Hayek's 'The Road to Serfdom'. Second, it demonstrates that
      senior Conservatives' emancipatory rhetoric in opposition after 1945 was neither
      a simple continuation of these themes nor primarily a response to the public's
      growing antipathy towards rationing and controls. Rather, such rhetoric was a
      complex response to Britain's immediate economic difficulties and the political
      challenges presented by austerity. Finally, the article sheds new light on the
      strategy that governed the party's campaigns in 1950 and 1951. Churchill and
      others' calls to 'set the people free' stemmed from a belief that the rhetorical
      opportunity lay in reconciling liberty with security. In that sense, the
      leadership had moved beyond begrudging compromises with the 'Attleean settlement'
      and was instead attempting to define a new identity within the parameters of the
      welfare state.

PMID- 29036717
TI  - EVALUATION OF OCCUPATIONAL RADIATION DOSE IN TRANSCATHETER AORTIC VALVE
      IMPLANTATION.
AB  - Occupational doses during fluoroscopy in interventional procedures vary largely
      (Kim et al. (Occupational radiation doses to operators performing cardiac
      catheterization procedures. Health Phys. 2008;94:211-227)). In transcatheter
      aortic valve implantation, the operators' positions and use of radiation
      shielding are particularly related to the entry choice on the patient's heart.
      This study evaluates how occupational doses depend on operator positioning during
      transfemoral and transaortal access. Occupational dosimetric readings were
      collected with electronic dosemeters on two cardiothoracic surgeons and one
      cardiologist during 31 procedures. The findings were significantly higher body
      doses and eye lens doses to the surgeons during transaortal access compared to
      transfemoral access. The median equivalent eye lens dose per procedure received
      by the cardiologists was 0.05-0.06 mSv; hence, the cardiologists should wear
      protective eye wear to prevent reaching the proposed annual dose limit of 20 mSv
      to the eye lens. Surgeons ought to use protective eye wear as well, and should
      only perform a restricted number of transcatheter aortic valve implantations with
      transaortal access annually.

PMID- 29036718
TI  - Glutamatergic Response to Heat Pain Stress in Schizophrenia.
AB  - Regulation of stress response involves top-down mechanisms of the frontal-limbic
      glutamatergic system. As schizophrenia is associated with glutamatergic
      abnormalities, we hypothesized that schizophrenia patients may have abnormal
      glutamatergic reactivity within the dorsal anterior cingulate cortex (dACC), a
      key region involved in perception of and reaction to stress. To test this, we
      developed a somatic stress paradigm involving pseudorandom application of safe
      but painfully hot stimuli to the forearm of participants while they were
      undergoing serial proton magnetic resonance spectroscopy to measure changes in
      glutamate and glutamine levels in the dACC. This paradigm was tested in a sample
      of 21 healthy controls and 23 patients with schizophrenia. Across groups,
      glutamate levels significantly decreased following exposure to thermal pain,
      while ratio of glutamine to glutamate significantly increased. However,
      schizophrenia patients exhibited an initial increase in glutamate levels during
      challenge that was significantly different from controls, after controlling for
      heat pain tolerance. Furthermore, in patients, the acute glutamate response was
      positively correlated with childhood trauma (r = .41, P = .050) and inversely
      correlated with working memory (r = -.49, P = .023). These results provide
      preliminary evidence for abnormal glutamatergic response to stress in
      schizophrenia patients, which may point toward novel approaches to understanding
      how stress contributes to the illness.

PMID- 29036719
TI  - ChannelsDB: database of biomacromolecular tunnels and pores.
AB  - ChannelsDB (http://ncbr.muni.cz/ChannelsDB) is a database providing information
      about the positions, geometry and physicochemical properties of channels (pores
      and tunnels) found within biomacromolecular structures deposited in the Protein
      Data Bank. Channels were deposited from two sources; from literature using manual
      deposition and from a software tool automatically detecting tunnels leading to
      the enzymatic active sites and selected cofactors, and transmembrane pores. The
      database stores information about geometrical features (e.g. length and radius
      profile along a channel) and physicochemical properties involving polarity,
      hydrophobicity, hydropathy, charge and mutability. The stored data are
      interlinked with available UniProt annotation data mapping known mutation effects
      to channel-lining residues. All structures with channels are displayed in a clear
      interactive manner, further facilitating data manipulation and interpretation. As
      such, ChannelsDB provides an invaluable resource for research related to
      deciphering the biological function of biomacromolecular channels.

PMID- 29036720
TI  - The Relationship Between Clinical and Personal Recovery in Patients With
      Schizophrenia Spectrum Disorders: A Systematic Review and Meta-analysis.
AB  - Patients describe experiencing personal recovery despite ongoing symptoms of
      psychosis. The aim of the current research was to perform a meta-analysis
      investigating the relationship between clinical and personal recovery in patients
      with schizophrenia spectrum disorders. A comprehensive OvidSP database search was
      performed to identify relevant studies. Correlation coefficients of the
      relationship between clinical and personal recovery were retrieved from primary
      studies. Meta-analyses were performed, calculating mean weighted effect sizes for
      the association between clinical and personal recovery, hope, and empowerment.
      Additionally, associations between positive, negative, affective symptoms,
      general functioning, and personal recovery were investigated. The results show
      that heterogeneity across studies was substantial. Random effect meta-analysis of
      the relationship between symptom severity and personal recovery revealed a mean
      weighted correlation coefficient of r = -.21 (95% CI = -0.27 to -0.14, P < .001).
      We found the following mean weighted effect size for positive symptoms r = -.20
      (95% CI = -0.27 to -0.12, P < .001), negative symptoms r = -.24 (95% CI = -0.33
      to -0.15, P < .001), affective symptoms r = -.34 (95% CI = -0.44 to -0.24, P <
      .001) and functioning r = .21 (95% CI = -0.09 to 0.32, P < .001). The results
      indicate a significant small to medium association between clinical and personal
      recovery. Psychotic symptoms show a smaller correlation than affective symptoms
      with personal recovery. These findings suggest that clinical and personal
      recovery should both be considered in treatment and outcome monitoring of
      patients with schizophrenia spectrum disorders.

PMID- 29036722
TI  - Home on the (expanding) range: evaluating the effectiveness of a novel host's
      induced defenses against the mountain pine beetle-fungal complex.

PMID- 29036723
TI  - Converting from Transdermal to Buccal Formulations of Buprenorphine: A
      Pharmacokinetic Meta-Model Simulation in Healthy Volunteers.
AB  - Objective: To develop a model to predict buprenorphine plasma concentrations
      during transition from transdermal to buccal administration. Design: Population
      pharmacokinetic model-based meta-analysis of published data. Methods: A model
      based meta-analysis of available buprenorphine pharmacokinetic data in healthy
      adults, extracted as aggregate (mean) data from published literature, was
      performed to explore potential conversion from transdermal to buccal
      buprenorphine. The time course of mean buprenorphine plasma concentrations
      following application of transdermal patch or buccal film was digitized from
      available literature, and a meta-model was developed using specific
      pharmacokinetic parameters (e.g., absorption rate, apparent clearance, and
      volumes of distribution) derived from analysis of pharmacokinetic data for
      intravenously, transdermally, and buccally administered buprenorphine. Results:
      Data from six studies were included in this analysis. The final transdermal
      absorption model employed a zero-order input rate that was scaled to reflect a
      nominal patch delivery rate and time after patch application (with decline in
      rate over time). The transdermal absorption rate constant became zero following
      patch removal. Buccal absorption was a first-order process with a time lag and
      bioavailability term. Simulations of conversion from transdermal 20 mcg/h and 10
      mcg/h to buccal administration suggest that transition can be made rapidly
      (beginning 12 hours after patch removal) using the recommended buccal formulation
      titration increments (75-150 mcg) and schedule (every four days) described in the
      product labeling. Conclusions: Computer modeling and simulations using a meta
      model built from data extracted from publications suggest that rapid and
      straightforward conversion from transdermal to buccal buprenorphine is feasible.

PMID- 29036721
TI  - Blood-Based Protein Changes in Childhood Are Associated With Increased Risk for
      Later Psychotic Disorder: Evidence From a Nested Case-Control Study of the ALSPAC
      Longitudinal Birth Cohort.
AB  - The identification of early biological changes associated with the psychotic
      disorder (PD) is important as it may provide clues to the underlying
      pathophysiological mechanisms. We undertook the first proteomic profiling of
      blood plasma samples of children who later develop a PD. Participants were
      recruited from the UK Avon Longitudinal Study of Parents and Children (ALSPAC)
      cohort who also participated in psychiatric assessment interviews at age 18.
      Protein expression levels at age 11 were compared between individuals who
      developed PD at age 18 (n = 37) with population-based age-matched controls (n =
      38). Sixty out of 181 plasma proteins profiled were found to be differentially
      expressed (P < .05) in children with an outcome of the PD. Thirty-four of these
      proteins were found to be differentially expressed following correction for
      multiple comparisons. Pathway analysis implicated the complement and coagulation
      cascade. A second, targeted proteomic approach was used to verify these findings
      in age 11 plasma from subjects who reported psychotic experiences at age 18 (n =
      40) in comparison to age-matched controls (n = 66). Our findings indicate that
      the complement and coagulation system is dysregulated in the blood during
      childhood before the development of the PD.

PMID- 29036724
TI  - Etiology and Clinical Characteristics of Community-Acquired Pneumonia with Airway
      Malacia in Children.
AB  - Objective: The objective of this article is to study the etiology of community
      acquired pneumonia in children with airway malacia. Methods: We retrospectively
      reviewed the medical records of 428 pneumonia patients. All patients underwent
      bronchoscopy, and bronchoalveolar lavage samples were processed for
      microbiological assessment. Results: In a total of 428 cases reviewed, 60 were
      found to have airway malacia. Pathogens were identified in 44 of the 60 specimens
      (73.3%), with 32 being single-pathogen infections. The most common pathogen was
      respiratory syncytial virus (RSV; 20%). Mixed-pathogen infections were observed
      in 12 patients. Airway malacia patients were younger than those without malacia
      (10.5 vs. 50 months, respectively; p < 0.001). Compared with those without airway
      malacia, wheezing, cyanosis and admission to the pediatric intensive care unit
      were more common in children with airway malacia and their hospital stay was
      longer. Conclusion: RSV was the most common pathogen in those with airway
      malacia. Airway malacia was found to aggravate infectious pneumonia.

PMID- 29036725
TI  - AN INTERNATIONAL COOPERATION BY USING AN ALL-ENCOMPASSING PASSIVE RADON MONITOR.
AB  - The recently developed radon film-badge makes it possible to measure radon
      indoors, in soil, in water and/or in aqueous media (e.g. mud). As a result of its
      wide response linearity, this monitor has been successfully used to measure radon
      in-water with concentrations from 10 to ~10 000 Bq/L. By exploiting the unique
      characteristics of this badge, a mini-survey has been carried out by Health
      Canada in which radon in water was measured from 12 private wells, as well as in
      tap water originating from the Ottawa River. Due to the widespread interest of
      different laboratories in using these passive monitors, laboratories were
      provided with plastic films to construct their own badges by using in-house CR-39
      detectors. Monitors were then irradiated by a known radon concentration at the
      National Institute of Radiation Metrology (ENEA)'s radon chamber and sent back to
      each laboratory for processing and counting. Even though these laboratories have
      been using different etching- and counting-procedures, the film-badge responses
      varied only within ~12%.

PMID- 29036726
TI  - CONTRIBUTION OF DIFFERENT PARTICLES MEASURED WITH TRACK ETCHED DETECTORS ONBOARD
      ISS.
AB  - Cosmic radiation consists of primary high-energy galactic and solar particles.
      When passing through spacecraft walls and astronauts' bodies, the spectrum
      becomes even more complex due to generating of secondary particles through
      fragmentation and nuclear interactions. Total radiation exposure is contributed
      by both these components. With an advantage, space research uses track etched
      detectors from the group of passive detectors visualizing the tracks of
      particles, in this case by etching. The detectors can discriminate between
      various components of cosmic radiation. A method is introduced for the separation
      of the different types of particles according to their range using track etched
      detectors. The method is demonstrated using detectors placed in Russian segment
      of the International Space Station in 2009. It is shown that the primary high
      energy heavy ions with long range contribute up to 56% of the absorbed dose and
      up to 50% to the dose equivalent.

PMID- 29036728
TI  - A Retrospective Study Evaluating the Effect of Low Doses of Perineural
      Dexamethasone on Ropivacaine Brachial Plexus Peripheral Nerve Block Analgesic
      Duration.
AB  - Objective: Examination of the effectiveness of perineural dexamethasone
      administered in very low and low doses on ropivacaine brachial plexus block
      duration. Design: Retrospective evaluation of brachial plexus block duration in a
      large cohort of patients receiving peripheral nerve blocks with and without
      perineural dexamethasone in a prospectively collected quality assurance database.
      Setting: A single academic medical center. Methods: A total of 1,942 brachial
      plexus blocks placed over a 16-month period were reviewed. Demographics, nerve
      block location, and perineural dexamethasone utilization and dose were examined
      in relation to block duration. Perineural dexamethasone was examined as none (0
      mg), very low dose (2 mg or less), and low dose (greater than 2 mg to 4 mg).
      Continuous catheter techniques, local anesthetics other than ropivacaine, and
      block locations with fewer than 15 subjects were excluded. Associations between
      block duration and predictors of interest were examined using multivariable
      regression models. A subgroup analysis of the impact of receiving dexamethasone
      on block duration within each block type was also conducted using a univariate
      linear regression approach. Results: A total of 1,027 subjects were evaluated.
      More than 90% of brachial plexus blocks contained perineural dexamethasone (<=4
      mg), with a median dose of 2 mg. Increased block duration was associated with
      receiving any dose of perineural dexamethasone (P < 0.0001), female gender (P =
      0.022), increased age (P = 0.048), and increased local anesthetic dose (P =
      0.01). In a multivariable model, block duration did not differ with very low- or
      low-dose perineural dexamethasone after controlling for other factors (P =
      0.420). Conclusion: Perineural dexamethasone prolonged block duration compared
      with ropivacaine alone; however, duration was not greater with low-dose compared
      with very low-dose perineural dexamethasone.

PMID- 29036727
TI  - Economic, Labor, and Regulatory Moderators of the Effect of Individual Placement
      and Support Among People With Severe Mental Illness: A Systematic Review and Meta
      analysis.
AB  - As Individual Placement and Support (IPS) has become the international standard
      for vocational rehabilitation of adults with serious mental illness, researchers
      must consider the relationship between IPS and local environments. This meta
      analysis used mixed-effects meta-regressions to assess the impact of site-level
      moderators on the likelihood that IPS recipients, compared with recipients of
      alternative vocational services, achieved competitive employment. Potential
      moderators included change in gross domestic product (GDP), local unemployment
      and unionization rates, and indices describing employment protection regulations,
      level of disability benefits compensation, and efforts to integrate people with
      disabilities into the workforce. Regulatory moderators represent facilitators and
      barriers to employment that may reinforce or detract from the effectiveness of
      IPS. Across 30 sites drawn from 21 randomized controlled trials in 12 countries
      (33% in the United States), IPS recipients were 2.31 (95% CI 1.99-2.69) times
      more likely to find competitive employment than recipients of alternative
      vocational rehabilitation services. The significant competitive-employment rate
      advantage of IPS over control services increased in the presence of weaker
      employment protection legislation and integration efforts, and less generous
      disability benefits. Policy makers should recognize and account for the fact that
      labor and disability regulations can create an arrangement of incentives that
      reduces the relative efficacy of supported employment.

PMID- 29036729
TI  - Reversal of lung fibrosis: an unexpected finding in survivor of acute respiratory
      distress syndrome.

PMID- 29036730
TI  - Calculation and Validation of the Response Matrix for a Neutron Multisphere
      Spectrometer with an Indium Central Detector.
AB  - Expansion of accelerator technologies into different application areas brings the
      need for neutron-field measurements in their vicinity. The measurements of
      neutron energy spectra and neutron dose rates can be done with the aid of neutron
      multisphere spectrometers with passive neutron detectors. In addition to the
      usually used thermoluminescent detectors and gold activation foils, another
      activation material-indium-can be considered. This paper presents a design of
      such an indium-based neutron multisphere spectrometer. Its response matrix was
      calculated with Monte Carlo code MCNP5 in the energy interval from 0.001 eV to
      about 20 MeV. The response matrix was validated with an Am-Be standard neutron
      source. MAXED code was used for neutron energy spectra unfolding. The values of
      the neutron fluence rate and neutron ambient dose equivalent rate in a reference
      point were calculated. The properties and advantages of indium for use in neutron
      multisphere spectrometry are discussed.

PMID- 29036732
TI  - Predictors of Poor Outcome in Neonates with Pyogenic Meningitis in a Level-Three
      Neonatal Intensive Care Unit of Developing Country.
AB  - Background: The mortality of neonatal pyogenic meningitis is reduced to 10-15%,
      but morbidity is unchanged. Methods: Primary objective is to determine the
      outcome, i.e. death or abnormal neurological examination (NE) at discharge and
      abnormal developmental quotient (DQ) at 3 months. Secondary objective is to find
      predictors of poor outcome. Results: In all, 89 neonates enrolled, 10 expired and
      24 neonates had abnormal NE at discharge. A total of 59 neonates came for follow
      up, 13 had DQ < 70. Prolonged shock (odds ratio, OR: 8.28; p = 0.001), coma (OR:
      4.3; p = 0.001), seizures (OR: 14; p = 0.012), mechanical ventilation (OR: 18.55;
      p = 0.00), orogastric feeding (OR: 2.78; p = 0.042) and electroencephalography
      (EEG; OR: 9.6; p = 0.00) predicted poor short-term outcome. Abnormal NE at
      discharge (OR: 15.6; p = 0.001), EEG (OR = 10.60; p = 0.00) and brainstem-evoked
      reflex audiometry (OR = 37.20, p = 0.00) predicted a low DQ at 3 months.
      Mortality and morbidity of neonates with Pyogenic Meningitis (PM) were similar to
      that in developed countries. Outcome depended on severity of the disease and NE
      at discharge.

PMID- 29036733
TI  - [A rare differential diagnosis of jugulotympanic paraganglioma].

PMID- 29036731
TI  - Rethinking Body Ownership in Schizophrenia: Experimental and Meta-analytical
      Approaches Show no Evidence for Deficits.
AB  - Schizophrenia is a severe psychiatric disorder, in which patients experience an
      abnormal sense of self. While deficits in sensorimotor self-representation
      (agency) are well documented in schizophrenia, less is known about other aspects
      of bodily self-representation (body ownership). Here, we tested a large cohort (N
      = 59) of chronic schizophrenia patients and matched controls (N = 30) on a well
      established body illusion paradigm, the Full Body Illusion (FBI). In this
      paradigm, changes in body ownership are induced through prolonged multisensory
      stimulation, in which participants are stroked on their back while seeing the
      stroking on the back of a virtual body. When the felt and seen stroking are
      synchronous, participants typically feel higher identification with the seen body
      as well as a drift in self-location towards it. However, when the stroking is
      asynchronous, no such changes occur. Our results show no evidence for abnormal
      body ownership in schizophrenia patients. A meta-analysis of previous work
      corroborates this result. Thus, while schizophrenia patients may be impaired in
      the sense of agency, their multisensory bodily self-representation, as tested
      here, seems to be unaffected by the illness.

PMID- 29036734
TI  - Benefit-Cost Analysis of Radiocesium Decorporation by a Prussian Blue Treatment
      and Stockpiling.
AB  - In the case of an attack by a "dirty bomb" with cesium-137 there is a risk of
      internal contamination. The excretion of cesium-137 can be enhanced by Prussian
      Blue (PB), and thus the committed effective dose be reduced. We analyzed the
      benefit and costs of PB decorporation treatment. We simulated the reduction of
      the radiological dose by PB treatment after cesium-137 incorporation by
      inhalation. The saving of life time was quantified using the monetary "value of a
      statistical life" (VSL). Treatment costs were based on the market price of PB in
      Germany. Moreover we considered the holding costs of stockpiling. The benefit of
      PB treatment increases with its duration up to about 90 days. If treatment
      initiation is delayed, the maximum achievable benefit is decreased. For a VSL of
      1.646 million ?, the net benefit of a 90-days treatment started 1 day after the
      incorporation remains positive up to a stockpiling duration of 10 years. If
      starting PB treatment as late as the 180th day after incorporation, the costs
      will surpass the benefit. We conclude that a prompt decision making and early
      treatment initiation greatly impacts on the medical but also economic efficiency
      of a PB treatment.

PMID- 29036735
TI  - Facile Synthesis and Characterization of L-Aspartic Acid Coated Iron Oxide
      Magnetic Nanoparticles (IONPs) For Biomedical Applications.
AB  - Natural L-aspartic acid coated iron oxide magnetic nanoparticles (Asp@IONPs) were
      prepared by a one pot, in-situ and green co-precipitation method in an aqueous
      medium. Functionalized iron oxide magnetic nanoparticles (IONPs) were
      characterized by Vibrating Sample Magnetometer (VSM), X-ray diffraction (XRD),
      differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy
      (FTIR), Scanning electron microscopy (SEM) and Transmission electron microscopy
      (TEM) techniques. Cellular toxicity of IONPs was also investigated on HEK-293
      cell lines. The results showed that the zeta potential of Asp@IONPs was about 
      21.1 mV and the average size was 17.80+/-3.09 nm. Cell toxicity results show that
      as prepared IONPs are biocompatible. Asp@IONPs show the possibility of using
      these nanoparticles in the development of in vitro and in vivo biomedical fields
      due to do not possess a toxic effect, good zeta-potential and related small and
      narrow size distribution.

PMID- 29036737
TI  - Hot Topics Issue.

PMID- 29036736
TI  - Pulmonary Hypertension in Patients with Congenital Diaphragmatic Hernia: Does
      Lung Size Matter?
AB  - PURPOSE:  The relationship between pulmonary hypoplasia and pulmonary arterial
      hypertension (PHTN) in patients with congenital diaphragmatic hernia (CDH)
      remains ill-defined. We hypothesized that prenatal estimates of lung size would
      directly correlate with PHTN severity. METHODS:  Infants with isolated CDH (born
      2004-2015) at a single institution were included. Estimates of lung size included
      observed-to-expected LHR (o:eLHR) and %-predicted lung volumes (PPLV =
      observed/predicted volumes). The primary outcome was severity of PHTN (grade 0-3)
      on echocardiography performed between day of life 3 and 30. RESULTS:  Among 62
      patients included, there was 32% mortality and 65% ECMO utilization. PPLV (odds
      ratio [OR] = 0.94 per 1 grade in PHTN severity, 95% confidence interval [CI] =
      0.89-0.98, p < 0.01) and o:eLHR (OR = 0.97, 95% CI = 0.94-0.99, p < 0.01) were
      significantly associated with PHTN grade. Among patients on ECMO, PPLV (OR =
      0.92, 95% CI = 0.84-0.99, p = 0.03) and o:eLHR (OR = 0.95, 95% CI = 0.92-0.99, p
      = 0.01) were more strongly associated with PHTN grade. PPLV and o:eLHR were
      significantly associated with the use of inhaled nitric oxide (iNO) (OR = 0.90,
      95% CI = 0.83-0.98, p = 0.01 and OR = 0.94, 95% CI = 0.91-0.98, p < 0.01,
      respectively) and epoprostenol (OR = 0.91, 95% CI = 0.84-0.99, p = 0.02 and OR =
      0.93, 95% CI = 0.89-0.98, p < 0.01, respectively). CONCLUSION:  Among infants
      with isolated CDH, PPLV, and o:eLHR were significantly associated with PHTN
      severity, especially among patients requiring ECMO. Prenatal lung size may help
      predict postnatal PHTN and associated therapies.

PMID- 29036738
TI  - Paternal Diet and Obesity: Effects on Reproduction.

PMID- 29036739
TI  - Investigational Medical Therapies for Endometriosis: Current Data and Future
      Trends.

PMID- 29036740
TI  - Pharmacologic Treatment of Polycystic Ovary Syndrome: Alternate and Future Paths.

PMID- 29036742
TI  - Acupuncture for Infertility in Women with Polycystic Ovary Syndrome: What Does It
      Add?

PMID- 29036743
TI  - Fresh versus Frozen Embryo Transfer in PCOS: Arguments for and Against.

PMID- 29036744
TI  - Robotics and Reproductive Surgery.

PMID- 29036741
TI  - The Effects of Aspirin in Gestation and Reproduction (EAGeR) Trial: A Story of
      Discovery.

PMID- 29036746
TI  - Erratum: Management of Endometriomas.

PMID- 29036748
TI  - [Not Available].

PMID- 29036745
TI  - Best Practices in Counseling Young Female Cancer Survivors on Reproductive
      Health.

PMID- 29036747
TI  - Prevention of multidrug-resistant infections from contaminated duodenoscopes:
      Position Statement of the European Society of Gastrointestinal Endoscopy (ESGE)
      and European Society of Gastroenterology Nurses and Associates (ESGENA).
AB  - Patients should be informed about the benefits and risks of endoscopic retrograde
      cholangiopancreatography (ERCP)Only specially trained and competent personnel
      should carry out endoscope reprocessing.Manufacturers of duodenoscopes should
      provide detailed instructions on how to use and reprocess their equipment.In the
      case of modifications to their equipment, manufacturers should provide updated
      instructions for use.Detailed reprocessing protocols based on the manufacturer's
      instructions for use should clearly lay out the different reprocessing steps
      necessary for each endoscope model.Appropriate cleaning equipment should be used
      for duodenoscopes in compliance with the manufacturer's instructions for use.
      Only purpose-designed, endoscope type-specific, single-use cleaning brushes
      should be used, to ensure optimal cleaning. As soon as the endoscope is withdrawn
      from the patient, bedside cleaning should be performed, followed by leak testing,
      thorough manual cleaning steps, and automated reprocessing, in order to: . Remove
      debris from external and internal surfaces;. . Prevent any drying of body fluids,
      blood, or debris;. . Prevent any formation of biofilms.. In addition to the leak
      test, visual inspection of the distal end as well as regular maintenance of
      duodenoscopes should be performed according to the manufacturer's instructions
      for use, in order to detect any damage at an early stage.The entire reprocessing
      procedure in endoscope washer-disinfectors (EWDs) should be validated according
      to the European and International Standard, EN ISO 15883. Routine technical tests
      of EWDs should be performed according to the validation reports.Microbiological
      surveillance of a proportion of the department's endoscopes should be performed
      every 3 months, with the requirement that all endoscopes used in the unit are
      tested at least once a year.In the case of suspected endoscopy-related infection,
      the relevant device (e. g., endoscope, EWD) should be taken out of service until
      adequate corrective actions have been taken. Outbreaks should be managed by a
      multidisciplinary team, including endoscopy, hygiene, and microbiology experts,
      manufacturers, and regulatory bodies, according to national standards and/or
      laws. In the case of suspected multidrug-resistant organism (MDRO) outbreaks,
      close cooperation between the endoscopy unit and the clinical health provider is
      essential (including infection control departments and hospital hygienists).

PMID- 29036749
TI  - [Paediatrics in light of the Convention on the Rights of the Child].
AB  - The United Nations Convention on the Rights of the Child not only grants
      comprehensive rights to children via international law, it also constitutes a
      legally binding framework under German federal law. With respect to health care,
      the convention establishes the "right of the child to the enjoyment of the
      highest attainable standard of health" and the principle that "the best interests
      of the child shall be a primary consideration" in all actions undertaken by
      public or private institutions. Here, some fundamental aspects of the convention
      and the monitoring of its implementation are summarized and current challenges in
      paediatric medicine in Germany are discussed in light of the convention.

PMID- 29036750
TI  - Does Postoperative Anticoagulation Therapy Lead to a Higher Success Rate for
      Microvascular Free-Tissue Transfer in the Head and Neck? A Systematic Review and
      Meta-Analysis.
AB  - BACKGROUND:  Due to limited evidence, it is unclear whether postoperative
      anticoagulation therapy may lead to higher success rates for microvascular free
      flap surgery in the head and neck. This review evaluated whether postoperative
      anticoagulation therapy can lead to a better result in head and neck
      reconstruction. METHODS:  PubMed, Embase, and the Cochrane Library were used to
      search for articles on the efficacy of postoperative antithrombotic therapy in
      free-flap transfer during head and neck reconstruction without language
      restrictions in February of 2017. A random-effects model was used to estimate the
      relative risk ratio (RR) with 95% confidence intervals (CIs). The measured
      outcomes were flap loss, thromboembolic events, and hematoma formation. RESULTS: 
      A total of 2,048 free-flap surgery procedures in the head and neck were analyzed.
      There was no significant difference in the occurrence of flap loss and
      thromboembolic events in the anticoagulation group compared with the
      nonanticoagulation group (RR = 1.25, 95% CI = 0.85-1.81, p = 0.26; and RR = 1.05,
      95% CI = 0.74-1.48, p = 0.79, respectively). The risk of hematoma was twice as
      high in the anticoagulation group than the nonanticoagulation group, which was
      statistically significant (RR = 2.02, 95% CI = 1.08-3.76, p = 0.03). CONCLUSION: 
      The findings from our meta-analysis indicate that postoperative anticoagulation
      therapy barely decreases the risks of flap loss and thromboembolic events in free
      flap surgery in the head and neck. However, it may significantly increase the
      risk of hematoma formation. Considering the limitations of this meta-analysis,
      additional high-quality, multicenter, prospective, randomized controlled studies
      are needed to confirm these findings.

PMID- 29036751
TI  - [Diagnosis and Management of Vestibular Schwannomas - An Interdisciplinary
      Challenge].
AB  - Vestibular schwannomas expand slowly in the internal auditory canal, in the
      cerebellopontine angle, inside the cochlear and the labyrinth. Larger tumors can
      displace and compress the brainstem. With an annual incidence of 1:100 000
      vestibular schwannoma represent 6-7% of all intracranial tumors. In the
      cerebellopontine angle they are by far the most neoplasm with 90% of all lesions
      located in this region. Magnetic resonance imaging (MRI), audiometry, and
      vestibular diagnostics are the mainstays of the clinical workup for patients
      harboring tumors. The first part of this paper delivers an overview of tumor
      stages, the most common grading scales for facial nerve function and hearing as
      well as a short introduction to the examination of vestibular function.Upholding
      or improving quality of life is the central concern in counseling and treating a
      patient with vestibular schwannoma. Preservation of neuronal function is
      essential and the management options - watchful waiting, microsurgery and
      stereotactic radiation - should be custom-tailored to the individual situation of
      the patient. Continuing interdisciplinary exchange is important to monitor
      treatment quality and to improve treatment results. Recently, several manuscripts
      and reviews have been published on the topic of vestibular schwanomma. On the
      occasion of the 88th annual meeting of the German Society of Oto-rhino
      laryngology, Head and Neck surgery a special volume of the journal "HNO" will be
      printed. Hence this presentation has been designed to deviate from the
      traditional standard which commonly consists of a pure literature review. The
      current paper was conceptually woven around a series of interdisciplinary cases
      which outlines examples for every stage of the disease that show characteristic
      results for management options to date. Systematic clinical decision pathways
      have been deduced from our experience and from results reported in the
      literature. These pathways are graphically outlined after the case presentations.
      Important criteria for decision making are size and growth rate of the tumor,
      hearing of the patient and the probability of total tumor resection with
      preservation of hearing and facial nerve function, age and co-morbidity of the
      patient, best possible control of vertigo and tinnitus and last but not least the
      patient's preference and choice. In addition to this, the experience and the
      results of a given center with each treatment modality will figure in the
      decision making process.We will discuss findings that are reported in the
      literature regarding facial nerve function, hearing, vertigo, tinnitus, and
      headache and reflect on recent studies on their influence on the patient's
      quality of life. Vertigo plays an essential role in this framework since it is an
      independent predictor of quality of life and a patient's dependence on social
      welfare.Pathognomonic bilateral vestibular schwannoma that occur in patients
      suffering from neurofibromatosis typ-2 (NF2) differ from spontaneous unilateral
      tumors in their biologic behavior. Treatment of neurofibromatosis type-2 patients
      requires a multidisciplinary team, especially because of the multitude of
      separate intracranial and spinal lesions.Off-label chemotherapy with Bevacizumab
      can stabilize tumor size of vestibular schwannomas and even improve hearing over
      longer periods of time. Hearing rehabilitation in NF2 patients can be achieved
      with cochlea and auditory brainstem implants.

PMID- 29036752
TI  - Breast Cancer Screening: Updated Recommendations of the Brazilian College of
      Radiology and Diagnostic Imaging, Brazilian Breast Disease Society, and Brazilian
      Federation of Gynecological and Obstetrical Associations.

PMID- 29036753
TI  - Erratum: Physical Activity during Pregnancy: Recommendations and Assessment
      Tools.

PMID- 29036754
TI  - Patellofemoral Cartilage Restoration: Indications, Techniques, and Outcomes of
      Autologous Chondrocytes Implantation, Matrix-Induced Chondrocyte Implantation,
      and Particulated Juvenile Allograft Cartilage.
AB  - Focal chondral defects are common in the patellofemoral (PF) joint and can
      significantly impair the quality of life. The autologous chondrocytes
      implantation (ACI) technique has evolved over the past 20 years: the first
      generation technique involves the use of a periosteal patch, the second
      generation technique (collagen-cover) uses a type I/III collagen membrane, and
      the newest third-generation technique seeds and cultivates the collagen membrane
      with chondrocytes prior to implantation and is referred to as matrix-induced
      autologous chondrocyte implantation. Particulated juvenile allograft cartilage
      (PJAC) (DeNovo NT) is minced cartilage allograft from juvenile donors. A thorough
      physical exam is important, especially for issues affecting the PF joint, to
      isolate the location and source of pain, and to identify associated pathologies.
      Imaging studies allow further characterization of the lesions and identification
      of associated pathologies and alignment. Conservative management should be
      exhausted before proceeding with surgical treatment. Steps of surgical treatment
      are diagnostic arthroscopy and biopsy, chondrocytes culture and chondrocyte
      implantation for the three generations of ACI, and diagnostic arthroscopy and
      implantation for PJAC. The techniques and their outcomes will be discussed in
      this article.

PMID- 29036755
TI  - Use of Fresh Osteochondral Allografts in the Patellofemoral Joint.
AB  - Fresh osteochondral allograft (OCA) transplantation has become a mainstay for the
      treatment of osteochondral defects in the tibiofemoral joint. With excellent
      outcomes and high survival times, this technology has recently become more
      interesting for use in the patellofemoral (PF) joint. This review article will
      point out the historical difficulties that the use of fresh OCA poses. With newer
      surgical approaches and a better understanding of the mechanical requirements of
      the PF joint, the use of OCA transplantation has shown increasingly better
      results. Illustrating the technique for the preparation and implantation of
      single plug allografts and bulk allografts to the trochlea and patella as well as
      the analysis of the available literature, we point out the current state of the
      art as well as potentially achievable long-term results. Finally, we will point
      out emerging technology seeking to further develop the use of allograft
      technology in patellofemoral chondral defects.

PMID- 29036756
TI  - Acupuncture or acupressure for induction of labour.
AB  - BACKGROUND: This is one of a series of reviews of methods of cervical ripening
      and labour induction. The use of complementary therapies is increasing. Women may
      look to complementary therapies during pregnancy and childbirth to be used
      alongside conventional medical practice. Acupuncture involves the insertion of
      very fine needles into specific points of the body. Acupressure is using the
      thumbs or fingers to apply pressure to specific points. The limited observational
      studies to date suggest acupuncture for induction of labour has no known adverse
      effects to the fetus, and may be effective. However, the evidence regarding the
      clinical effectiveness of this technique is limited. OBJECTIVES: To determine,
      from the best available evidence, the effectiveness and safety of acupuncture and
      acupressure for third trimester cervical ripening or induction of labour. SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (30 November 2016), PubMed (1966 to 25 November 2016), ProQuest
      Dissertations & Theses (25 November 2016), CINAHL (25 November 2016), Embase (25
      November 2016), the WHO International Clinical Trials Registry Portal (ICTRP) (3
      October 2016), and bibliographies of relevant papers. SELECTION CRITERIA:
      Randomised controlled trials comparing acupuncture or acupressure, used for third
      trimester cervical ripening or labour induction, with placebo/no treatment or
      other methods on a predefined list of labour induction methods. DATA COLLECTION
      AND ANALYSIS: Two review authors independently assessed trials for inclusion and
      risk of bias, extracted data, and checked them for accuracy. The quality of the
      evidence was assessed using GRADE. MAIN RESULTS: This updated review includes 22
      trials, reporting on 3456 women. The trials using manual or electro-acupuncture
      were compared with usual care (eight trials, 760 women), sweeping of membranes
      (one trial, 207 women), or sham controls (seven trials, 729 women). Trials using
      acupressure were compared with usual care (two trials, 151 women) or sham
      controls (two trials, 239 women). Many studies had a moderate risk of
      bias.Overall, few trials reported on primary outcomes. No trial reported vaginal
      delivery not achieved within 24 hours and uterine hyperstimulation with fetal
      heart rate (FHR) changes. Serious maternal and neonatal death or morbidity were
      only reported under acupuncture versus sham control. Acupuncture versus sham
      control There was no clear difference in caesarean sections between groups
      (average risk ratio (RR) 0.80, 95% confidence interval (CI) 0.56 to 1.15, eight
      trials, 789 women; high-quality evidence). There were no reports of maternal
      death or perinatal death in the one trial that reported this outcome. There was
      evidence of a benefit from acupuncture in improving cervical readiness for labour
      (mean difference (MD) 0.40, 95% CI 0.11 to 0.69, one trial, 125 women), as
      measured by cervical maturity within 24 hours using Bishop's score. There was no
      evidence of a difference between groups for oxytocin augmentation, epidural
      analgesia, instrumental vaginal birth, meconium-stained liquor, Apgar score < 7
      at five minutes, neonatal intensive care admission, maternal infection,
      postpartum bleeding greater than 500 mL, time from the trial to time of birth,
      use of induction methods, length of labour, and spontaneous vaginal birth.
      Acupuncture versus usual care There was no clear difference in caesarean sections
      between groups (average RR 0.77, 95% CI 0.51 to 1.17, eight trials, 760 women;
      low-quality evidence). There was an increase in cervical maturation for the
      acupuncture (electro) group compared with control (MD 1.30, 95% CI 0.11 to 2.49,
      one trial, 67 women) and a shorter length of labour (minutes) in the usual care
      group compared to electro-acupuncture (MD 124.00, 95% CI 37.39 to 210.61, one
      trial, 67 women).There appeared be a differential effect according to type of
      acupuncture based on subgroup analysis. Electro-acupuncture appeared to have more
      of an effect than manual acupuncture for the outcomes caesarean section (CS), and
      instrumental vaginal and spontaneous vaginal birth. It decreased the rate of CS
      (average RR 0.54, 95% CI 0.37 to 0.80, 3 trials, 327 women), increased the rate
      of instrumental vaginal birth (average RR 2.30, 95%CI 1.15 to 4.60, two trials,
      271 women), and increased the rate of spontaneous vaginal birth (average RR 2.06,
      95% CI 1.20 to 3.56, one trial, 72 women). However, subgroup analyses are
      observational in nature and so results should be interpreted with caution.There
      were no clear differences between groups for other outcomes: oxytocin
      augmentation, use of epidural analgesia, Apgar score < 7 at 5 minutes, neonatal
      intensive care admission, maternal infection, perineal tear, fetal infection,
      maternal satisfaction, use of other induction methods, and postpartum bleeding
      greater than 500 mL. Acupuncture versus sweeping if fetal membranes One trial of
      acupuncture versus sweeping of fetal membranes showed no clear differences
      between groups in caesarean sections (RR 0.64, 95% CI 0.34 to 1.22, one trial,
      207 women, moderate-quality evidence), need for augmentation, epidural analgesia,
      instrumental vaginal birth, Apgar score < 7 at 5 minutes, neonatal intensive care
      admission, and postpartum bleeding greater than 500 mL. Acupressure versus sham
      control There was no evidence of benefit from acupressure in reducing caesarean
      sections compared to control (RR, 0.94, 95% CI 0.68 to 1.30, two trials, 239
      women, moderate-quality evidence). There was no evidence of a clear benefit in
      reduced oxytocin augmentation, instrumental vaginal birth, meconium-stained
      liquor, time from trial intervention to birth of the baby, and spontaneous
      vaginal birth. Acupressure versus usual care There was no evidence of benefit
      from acupressure in reducing caesarean sections compared to usual care (RR 1.02,
      95% CI 0.68 to 1.53, two trials, 151 women, moderate-quality evidence). There was
      no evidence of a clear benefit in reduced epidural analgesia, Apgar score < 7 at
      5 minutes, admission to neonatal intensive care, time from trial intervention to
      birth of the baby, use of other induction methods, and spontaneous vaginal birth.
      AUTHORS' CONCLUSIONS: Overall, there was no clear benefit from acupuncture or
      acupressure in reducing caesarean section rate. The quality of the evidence
      varied between low to high. Few trials reported on neonatal morbidity or maternal
      mortality outcomes. Acupuncture showed some benefit in improving cervical
      maturity, however, more well-designed trials are needed. Future trials could
      include clinically relevant safety outcomes.

PMID- 29036757
TI  - A Case of Medullary Infarction Presented Initial Symptoms Similar to Meniere's
      Disease.
AB  - Fluctuating hearing loss and vertigo are the typical presentations of Meniere's
      disease. However, it is unusual that fluctuating hearing loss and vertigo are
      caused by vertebral artery occlusion or cerebral infarction. Here, we described
      the case of a 54-year-old male patient with hypertension and diabetes mellitus
      who presented with fluctuating hearing loss in his left ear and severe whirling
      type dizziness without associated neurological signs or symptoms. Temporal
      magnetic resonance imaging (MRI) was normal. He was diagnosed with a possible
      Meniere's disease and started conservative treatment. Eight years later, the
      patient developed dysarthria and left-side weakness. Brain MRI revealed right
      anterior medullary infarction, and cerebral angiography showed occlusion of the
      right vertebral artery. In this case, we attempted to review the initial imaging
      study and reported the characteristics of the case.

PMID- 29036758
TI  - Comparison of Single-Task versus Dual-Task for Listening Effort.
AB  - BACKGROUND AND OBJECTIVES: Depending on the kind of task and/or material,
      listeners sometimes need to pay attention to understand communication. The
      present study aimed to estimate a listener's amount of effort needed to
      understand communication by using recognition score and response time as a
      function of signal-to-noise ratio (SNR) and to confirm his/ her task dependency
      for listening effort. SUBJECTS AND METHODS: Forty-eight young adults with normal
      hearing participated in the study. As stimuli, Korean Speech Perception in Noise
      test without a question tag and three consecutive digits were used for sentence
      recognition (or single-task) and arithmetic (or dual-task), respectively. Both
      tasks were measured in quiet and under four SNR (i.e., 0, -4, -8, -12 dB)
      conditions. Their outcomes were analyzed and compared in terms of percent correct
      and response time. RESULTS: Sentence recognition scores and arithmetic scores
      decreased as the level of noise increased. Response time for sentence recognition
      decreased as noise increased, whereas the response time for arithmetic increased
      as noise increased. In addition, there was a negative correlation between error
      percent and response time in the sentence recognition. Conversely, a positive
      correlation between error percent and response time appeared in the arithmetic
      test. CONCLUSIONS: Listening effort showed a different pattern based on the kind
      of task, single vs. dual, while the dual-task required greater effort from the
      listener.

PMID- 29036759
TI  - Can A Sudden Sensorineural Hearing Loss Occur Due to Miliary Tuberculosis?
AB  - Miliary tuberculosis is a severe form of tuberculosis resulting from
      dissemination of Mycobacterium tuberculosis bacilli. Since symptoms appearing in
      patients due to miliary TB are diverse and atypical, depending on the site of
      invasion, early diagnosis and treatment are important. A paradoxical response of
      tuberculosis is a rare phenomenon and it can be a clinical difficulty to
      treatment especially when involving the central nervous system. We present a case
      report with a review of related literature about the patient who developed sudden
      hearing loss due to tuberculosis infection in vestibulocochlear area.

PMID- 29036760
TI  - The effects of downhill and uphill exercise training on osteogenesis-related
      factors in ovariectomy-induced bone loss.
AB  - PURPOSE: Recent evidence suggests that regular exercise training plays a decisive
      role in maintaining homeostasis and promoting muscle and skeletal formation.
      However, the effect of downhill exercise training on osteogenesis-related factors
      is not well understood. METHODS: Thus, we investigated the effect of uphill and
      downhill training on ovariectomy (OVX)-induced bone loss. After ovary removal,
      the exercise method performed included uphill (16 m/min, +15 degrees ) and
      downhill training (16 m/min, -15 degrees ) for 60 min/day and 5 days/week,
      respectively, for 8 weeks. RESULTS: Our results showed that both uphill and
      downhill training significantly decreased the body weight, total cholesterol, and
      creatine kinase (CK) levels in the context of OVX-induced bone loss. On the
      contrary, levels of an osteogenesis indicator, osteocalcin and alkaline
      phosphatase were elevated. Consequently, the uphill and downhill training reduced
      OVX- induced bone loss in the distal femoral metaphysis. Likewise, the bone
      microstructure in OVX-induced bone loss was enhanced upon training. In
      particular, the inhibition of RANKL-induced osteoclast formation and osteoclast
      specific gene expression improved upon downhill training compared to uphill
      training. CONCLUSION: These results suggest that the uphill and downhill exercise
      types appeared to positively affect the expression of osteogenesis-related
      factors along with bone density and microstructure. Particularly, the downhill
      training has more beneficial effects on the maintenance of homeostasis during
      bone formation.

PMID- 29036761
TI  - Effects of conjugated linoleic acid/n-3 and resistance training on muscle quality
      and expression of atrophy-related ubiquitin ligases in middle-aged mice with high
      fat dietinduced obesity.
AB  - PURPOSE: To investigate the effects of conjugated linoleic acid (CLA)/n-3
      supplements and resistance exercise training (RT) for 20 weeks on muscle quality
      and genes related to protein synthesis/degradation in middle-aged mice with high
      fat diet (HFD)-induced obesity. METHODS: Nine-month-old C57BL/6 male mice were
      randomly assigned to five groups: 1) normal diet (C), 2) high-fat diet (H), 3)
      H+RT (HRT), 4) H+CLA/n-3 (H-CN), and 5) H+RT+CLA/n-3 (H-RTCN). HFD groups were
      given a diet containing 60% fat for 20 weeks, and exercised groups underwent
      progressive RT using weighted ladder climbing. The CLA/n-3 mixed diet contained
      1% CLA and 1% n-3. Grip strength was assessed, and triceps were removed. RT-PCR
      was used to analyze transcript levels. RESULTS: Grip strength of the H group was
      significantly lower than that of the C group; however, those in the H-CN, H-RT,
      and H-RTN groups were significantly greater than that in the H group. However,
      the muscle quality was significantly greater only in the H-RT group compared with
      the H and H-CN groups. Akt expression decreased in the H-CN, H-RT, and H-RTCN
      groups compared with those in the C and H groups, whereas mammalian target of
      rapamycin expression increased in the H, H-CN, H-RT, and H-RTCN groups compared
      with that in the C group. However, atrogin1 was significantly downregulated in
      the H-RTCN group compared with that in the H and H-CN groups, and MuRF1
      expression was also decreased in the H-RT and H-RTCN groups. Interestingly,
      atrogin1 and MuRF1 were downregulated in the H-RTCN group compared with that in
      the H-CN group. CONCLUSION: HFD-mediated gene expression involved in protein
      degradation was attenuated following 20-week RT with CLA/n-3. Furthermore, RT
      with or without CLA/n-3 improved grip strength and muscle quality in middle-aged
      mice during HFD. Therefore, RT with CLA/n-3 during HFD may improve muscle
      strength and quality by suppressing protein degradation.

PMID- 29036762
TI  - Low-intensity aerobic exercise training: inhibition of skeletal muscle atrophy in
      high-fat-diet-induced ovariectomized rats.
AB  - PURPOSE: Postmenopausal women are highly susceptible to diseases, such as
      obesity, type 2 diabetes, osteoporosis, or skeletal muscle atrophy and many
      people recognize the need for regular physical activity. Aerobic exercise
      training is known to improve the oxidative capacity and insulin sensitivity of
      skeletal muscles. This study aimed to investigate the role of low-intensity
      aerobic exercise training on skeletal muscle protein degradation or synthesis in
      the plantaris muscles of high-fat-fed ovariectomized rats. METHODS:
      Ovariectomized female rats were divided into two groups: a high-fat diet
      sedentary group (HFD), and a high-fat diet-aerobic exercise group (HFD+EX). The
      exercise group exercised aerobically on a treadmill 5 days/week for 8 weeks. The
      rats progressively ran 30 min/day at 15 m/min, up to 40 min/day at 18 m/min, 0%
      slope, in the last 4 weeks. RESULTS: Although aerobic exercise led to
      significantly increased AMP-activated protein kinase (AMPK) phosphorylation at
      Thr172, phosphorylation of the mammalian target of rapamycin (mTOR) substrate
      Thr389 S6K1 level did not decrease. Additionally, even though Akt activity did
      not increase at Ser473, the atrogin-1 level significantly decreased in the
      exercise group compared to the non-exercise group. Immunohistochemical staining
      revealed that high-fat-induced TSC2 protein expression was eliminated in response
      to aerobic exercise. CONCLUSION: These results suggest that aerobic exercise can
      inhibit skeletal muscle protein degradation, but it cannot increase protein
      synthesis in the plantaris muscle of high-fat-fed ovariectomized rats. Our
      findings have implications in understanding skeletal muscle mass maintenance with
      low intensity aerobic exercise in post-menopausal women.

PMID- 29036763
TI  - Effect of treadmill exercise on skeletal muscle autophagy in rats with obesity
      induced by a high-fat diet.
AB  - PURPOSE: This study aimed to investigate the effects of treadmill exercise on
      body weight, blood biochemistry, and autophagy. METHODS: Triglyceride, total
      cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol, insulin, and glucose levels were measured, the Homeostatic Model
      Assessment of Insulin Resistance (HOMA-IR) score was calculated, and the soleus
      muscle was analyzed for autophagy-related factors (Beclin-1, p62, LC3, Lamp-2) in
      rats with obesity induced by a high-fat diet. Eight-week-old Sprague Dawley rats
      were fed a high-fat diet for 35 weeks and then subjected to 10 weeks of treadmill
      exercise. The experimental group was divided into a Normal Diet-Sedentary (ND
      SED, n=8) group, an (High-Fat Diet-Sedentary (HF-SED, n=8) group, and an High-Fat
      Diet + Treadmill Exercise (HF-TE, n=8) group. The intensity of treadmill exercise
      was set as 8 m/min for 5 min, 11 m/min for 5 min, 15 m/min for 20 min, and 11
      m/min for the last 5 minutes. A glucose tolerance test was performed at the 2nd
      and 8th week of exercise by sampling of tail blood. RESULTS: With endurance
      exercise, the HFTE group showed a significant decrease in body weight, with
      improved blood biochemical indices and HOMA-IR scores, in comparison with the HF
      SED group. However, there was no significant difference in Beclin-1, p62, LC3,
      and Lamp-2 proteins as measured by autophagic flux in the soleus muscle.
      CONCLUSION: Treadmill exercise induced improvements in body weight, body fat, and
      biochemical indicators of obesity and Type 2 diabetes, but had no effect on
      autophagy in soleus muscle.

PMID- 29036764
TI  - Hippotherapy and neurofeedback training effect on the brain function and serum
      brain-derived neurotrophic factor level changes in children with attention
      deficit or/and hyperactivity disorder.
AB  - PURPOSE: The purpose of this study was to investigate the effect of hippotherapy
      and electroencephalography (EEG) neurofeedback on brain function and blood brain
      derived neurotrophic factor (BDNF) level in children with attention-deficit
      or/and hyperactivity disorder (ADHD). METHODS: Sixteen children with ADHD
      participated in this study and were randomly divided into 2 groups, a 1-time
      hippotherapy group (W1G, n = 8) and a 2-time hippotherapy group (W2G, n = 8). All
      the participants attended 8 weeks of hippotherapy program in the primary
      training, and then 7 children with ADHD attended 8 weeks of hippotherapy program
      combined with neurofeedback training in the secondary training. Blood BDNF levels
      were measured, and functional magnetic resonance imaging (fMRI) was performed.
      The EEG neurofeedback training program was used to train and measure
      psychological factors. RESULTS: The combined effect of hippotherapy and
      neurofeedback on BDNF level showed a decreased tendency in W1G (pretraining,
      1766.03 +/- 362.54 pg/ml; posttraining, 1630.65 +/- 276.70 pg/ml). However, the
      BDNF level of W2G showed an increased tendency (pretraining, 1968.28 +/- 429.08
      pg/ml; posttraining, 1976.28 +/- 425.35 pg/ml). Moreover, combined training
      showed a significant group x repetition interaction in W1G (pretraining, 1436.57
      +/- 368.76 pg/ml; posttraining, 1525.23 +/- 346.22 pg/ml; F = 3.870, p = 0.039).
      fMRI results showed that the left thalamus activity in both groups had a
      decreased tendency and a significantly lower change in W2G than in W1G (p <
      0.05). CONCLUSION: This study confirmed a significant increase in blood BDNF
      level after combined training, which may induce brain function improvement in
      children with ADHD.

PMID- 29036765
TI  - Development of an anaerobic threshold (HRLT, HRVT) estimation equation using the
      heart rate threshold (HRT) during the treadmill incremental exercise test.
AB  - PURPOSE: The purpose of this study was to develop a regression model to estimate
      the heart rate at the lactate threshold (HRLT) and the heart rate at the
      ventilatory threshold (HRVT) using the heart rate threshold (HRT), and to test
      the validity of the regression model. METHODS: We performed a graded exercise
      test with a treadmill in 220 normal individuals (men: 112, women: 108) aged 20-59
      years. HRT, HRLT, and HRVT were measured in all subjects. A regression model was
      developed to estimate HRLT and HRVT using HRT with 70% of the data (men: 79,
      women: 76) through randomization (7:3), with the Bernoulli trial. The validity of
      the regression model developed with the remaining 30% of the data (men: 33,
      women: 32) was also examined. RESULTS: Based on the regression coefficient, we
      found that the independent variable HRT was a significant variable in all
      regression models. The adjusted R2 of the developed regression models averaged
      about 70%, and the standard error of estimation of the validity test results was
      11 bpm, which is similar to that of the developed model. CONCLUSION: These
      results suggest that HRT is a useful parameter for predicting HRLT and HRVT.

PMID- 29036766
TI  - Resistance training increases fibroblast growth factor-21 and irisin levels in
      the skeletal muscle of Zucker diabetic fatty rats.
AB  - PURPOSE: Although the fibroblast growth factor-21 (FGF-21) and irisin roles are
      well demonstrated in metabolic disease, there have been no reports investigating
      the effect of resistance exercise on FGF-21 and irisin levels in diabetic
      skeletal muscles. Therefore, this study aimed to investigate the change of FGF-21
      and irisin levels in various skeletal muscles, and their association with muscle
      strength, following 8 weeks of resistance training using Zucker diabetic fatty
      rats (type 2 diabetic animal models). METHODS: Twenty-four male lean (Zucker lean
      control, ZLC) and diabetic (Zucker diabetic fatty, ZDF) rats (age, 8 weeks old)
      were separated into 3 groups, lean control (ZLC-Con, n=8), diabetic control (ZDF
      Con, n=8), and diabetic exercise-trained groups (ZDF-Ex, n=8). The rats in ZDF-Ex
      were trained to climb a 1-m vertical (85 degrees inclined) ladder with weights.
      Resistance training was performed with 10 repetitions/day for 12 weeks (3
      days/week). The skeletal muscle levels of FGF-21 and irisin were measured using
      enzyme-linked immunosorbent assays. RESULTS: The levels of FGF-21 in the soleus
      (SOL) and extensor digitorum longus muscles of ZDF-Ex were higher (p<0.05)
      compared to levels in ZDF-Con. Additionally, we found a significantly higher
      irisin level in the SOL muscles of ZDF-Ex compared to that in ZDF-Con. Moreover,
      we found that the levels of FGF-21 (R=0.532, p=0.02) and irisin (R=0.498, p=0.03)
      had significant correlations with grip strength. CONCLUSION: Based on these
      results, resistance training may be an efficient intervention for increasing FGF
      21 and irisin levels in type 2 diabetic (T2DM) skeletal muscles.

PMID- 29036767
TI  - The role of glycation in the pathogenesis of aging and its prevention through
      herbal products and physical exercise.
AB  - PURPOSE: Advanced glycation end products (AGEs) are non-enzymatic modifications
      of proteins or lipids after exposure to sugars. In this review, the glycation
      process and AGEs are introduced, and the harmful effects of AGEs in the aging
      process are discussed. METHODS: Results from human and animal studies examining
      the mechanisms and effects of AGEs are considered. In addition, publications
      addressing means to attenuate glycation stress through AGE inhibitors or physical
      exercise are reviewed. RESULTS: AGEs form in hyperglycemic conditions and/or the
      natural process of aging. Numerous publications have demonstrated acceleration of
      the aging process by AGEs. Exogenous AGEs in dietary foods also trigger organ
      dysfunction and tissue aging. Various herbal supplements or regular physical
      exercise have beneficial effects on glycemic control and oxidative stress with a
      consequent reduction of AGE accumulation during aging. CONCLUSION: The inhibition
      of AGE formation and accumulation in tissues can lead to an increase in lifespan.

PMID- 29036769
TI  - The management of irregular bleeding in women using contraception.
AB  - BACKGROUND: The pattern of menstrual bleeding seen in women during their
      reproductive years is the result of a finely tuned balance be-tween endogenous
      oestrogens, which stimulate the endometrial lining, and progesterone, which
      temporarily maintains that lining in anticipation of a pregnancy. Many women have
      expectations of a 'normal monthly' cycle, and may be wary of any-thing that has
      the potential to disrupt its regularity. From a clinical perspective, any
      alteration in vaginal bleeding may indicate underlying pathology, and lead to
      further investigation and management. OBJECTIVE: The aim of this article is to
      provide a practical approach to the investigation and management of altered
      vaginal bleeding patterns in women using various methods of contraception.
      DISCUSSION: Around 70% of Australian women of reproductive age use some form of
      contraception. Any discussion of 'normal bleeding' becomes even more complex
      given that modern contraceptive methods almost inevitably modify the pattern of
      bleeding experienced by the user.

PMID- 29036768
TI  - LARCs as first-line contraception - What can general practitioners advise young
      women?
AB  - BACKGROUND: The use of long-acting reversible contraceptives (LARCs) is globally
      accepted as a strategy that is successful in decreasing rates of unintended
      pregnancy, especially in very young women. Currently, Australia has very low
      uptake rates of LARC. OBJECTIVE: The aim of this paper is to explore the latest
      information on using LARCs as first-line contraception in young women.
      DISCUSSION: Low uptake of LARCs may be related to Australia's prevailing cultural
      norm of oral contraception, and practitioner and patient misperceptions of the
      safety and efficacy of LARC, which have been dispelled in recent years. LARCs are
      widely recommended by professional bodies and the World Health Organization (WHO)
      as first-line contraception for young women as they are safe, effective and
      reversible. Young women should be offered the choice of a LARC as part of a fully
      informed decision for their first form of contraception.

PMID- 29036770
TI  - Emergency contraception: Oral and intrauterine options.
AB  - BACKGROUND: Emergency contraception can be used to prevent pregnancy where
      contraception has not been used, or there has been contraceptive misuse or
      failure. Australian women have three options for emergency contraception: two
      types of oral pills (levonorgestrel [LNG]-containing pill and ulipristal acetate
      [UPA]) and the copper intrauterine device (IUD). Both pills are available from
      pharmacies without prescription, whereas the copper IUD requires insertion by a
      trained provider. OBJECTIVE: The objective of this article is to describe the
      indications, efficacy and contraindications for use of the three emergency
      contraceptive methods available in Australia. DISCUSSION: Emergency contraception
      can potentially reduce the risk of unplanned pregnancies. The oral methods have
      similar side effects, but UPA is more effective than LNG and can be used up to
      five days after intercourse. The copper IUD is the most effective method, and
      provides ongoing contraception for up to 10 years. Factors to consider when
      recommending one option over another include time since unprotected sex, body
      mass index and use of enzyme-inducing medicines.

PMID- 29036771
TI  - Oral hormonal contraception in special circumstances.
AB  - BACKGROUND: Despite the general consensus that long-acting reversible
      contraceptives (LARCs) are the most appropriate choice of contraception for most
      women, there are special circumstances when the contraceptive and non
      contraceptive needs of the patient are met by oral methods. OBJECTIVE: By using
      case histories, we seek to demonstrate the medical and practical complexities in
      managing contraceptive needs that may result in oral contraception being the most
      appropriate choice. The cases also illustrate the resources available to enable
      evidence-based management. DISCUSSION: Concurrent medical conditions and non
      contraceptive benefits of oral contraceptive methods will see the continued use
      of these medications for a significant minority of women. A comprehensive
      knowledge of the rapidly developing evidence regarding medical eligibility and
      indications for usage is required. Reference to the already highly developed and
      easily accessible evidence bases ensures best practice for the women and families
      who seek advice.

PMID- 29036773
TI  - A young woman with yellow hands and secondary amenorrhoea.

PMID- 29036772
TI  - Non-invasive prenatal testing.
AB  - BACKGROUND: Non-invasive prenatal testing (NIPT), also known as cell-free DNA
      testing and non-invasive prenatal screening (NIPS), is an important addition to
      the range of screening tests for fetal chromosomal abnormalities. For trisomy 21
      in particular, NIPT is superior to other screening modalities. However, NIPT has
      limitations and complexities that requesting clinicians and their patients should
      understand. OBJECTIVE: This review article will briefly describe the technical
      basis of NIPT assays and compare the performance characteristics of NIPT with
      existing screening tests. The clinical use of NIPT will also be discussed.
      DISCUSSION: NIPT is now an established option for antenatal screening for trisomy
      21, 18, 13 and other selected chromosomal abnormalities. If used appropriately,
      it increases the detection rate for fetal chromosomal abnormalities, while
      decreasing the number of invasive tests required. An understanding of the
      scientific basis of NIPT, and the appropriate clinical use and limitations, will
      enable medical practitioners to provide optimal antenatal screening.

PMID- 29036774
TI  - A suspicious haematoma.

PMID- 29036775
TI  - Subcutaneous finger nodules.

PMID- 29036777
TI  - Growing and retaining general practice research leaders in Australia: How can we
      do better?
AB  - BACKGROUND: The aim of this study was to explore the experiences of Australian
      general practitioners (GPs) with a Doctor of Philosophy (PhD) about their choice
      to abandon or pursue an academic career. METHODS: A qualitative study of 18 GPs
      (PhD obtained between 2006 and 2016) was conducted. Semi-structured telephone
      interviews were transcribed and analysed using concurrent thematic analysis.
      RESULTS: General practice researchers faced insecure career pathways. They often
      work in isolation, there is a lack of critical mass, and research was often
      described as a hobby (ie unfunded, done from home). Solutions included expanding
      academic general practice registrar positions to include advanced research
      training, building professional networks, mentoring, and better marketing of
      general practice research. DISCUSSION: Focused investment in developing clear and
      sustainable career pathways is essential to nurture and retain general practice
      researchers and research leaders. The research culture and professional standing
      of general practice researchers also need to improve. Support from professional
      bodies and colleagues, and enabling research collaborations, are key.

PMID- 29036776
TI  - Lifestyle risk factors and corresponding levels of clinical advice and
      counselling in general practice.
AB  - BACKGROUND: The objective of this study was to examine prevalence rates of
      lifestyle risk factors in the Western Victorian Primary Health Network (WV PHN)
      general practice patient population and the corresponding levels of clinical
      advice and counselling. METHODS: Analysed data from the Bettering the Evaluation
      and Care of Health (BEACH) program from April 2011 to March 2015 were examined,
      providing a comparison of three geographical areas of general practice patients:
      WV PHN, Victoria and Australia. RESULTS: Rates of clinical advice and counselling
      for diet and exercise provided by general practitioners (GPs) in the WV PHN
      network were significantly lower than Victorian and Australian rates, despite the
      region's higher obesity rates. Smoking rates were higher in the WV PHN compared
      with Australia, but there was no difference in the levels of smoking cessation
      advice disseminated. Across all regions, one in four patients drank alcohol at
      hazardous levels. DISCUSSION: GPs in rural practice require further support,
      encouragement and resources to provide diet and exercise advice to their patients
      more frequently.

PMID- 29036778
TI  - Electronic clinical decision support tool for the evaluation of cardiovascular
      risk in general practice: A pilot study.
AB  - BACKGROUND: Cardiovascular disease (CVD) is a major cause of death in Australia.
      Electronic medical record (EMR)-based clinical decision support (CDS) tools have
      the potential to support absolute CVD risk (ACVDR) evaluation and management. The
      objective of this study was to test the acceptability and feasibility of the
      Treat to Target CVD (T3CVD), an EMR-based CDS tool, for the evaluation of ACVDR
      in general practice. METHODS: Five general practitioners (GPs) piloted the T3CVD
      tool in their clinic. Interviews with the clinicians explored the acceptability
      and feasibility of the T3CVD tool. RESULTS: The T3CVD tool was acceptable and, in
      the small pilot, was shown to have the capacity to support GPs in ACVDR
      assessment and management, and to encourage patient participation and motivation.
      Technical and structural factors important to ensure feasibility of the tool were
      identified. DISCUSSION: With further development, the T3CVD tool has the
      potential to improve ACVDR assessment and management in primary care.

PMID- 29036779
TI  - Barriers to effective conversations regarding overweight and obesity in regional
      Victoria.
AB  - BACKGROUND: General practitioners (GPs) have a crucial role to play in engaging
      patients in discussions about overweight and obesity. However, such discussions
      are currently uncommon. The aim of this study was to examine how GPs in rural
      areas talk about overweight and obesity with their patients, specifically to
      identify key barriers to effective conversations. METHODS: This study used a
      qualitative methodology. Semi-structured interviews were conducted with GPs (n =
      7) and patients (n = 7) across two rural areas. RESULTS: Key barriers to
      effective conversations between GPs and patients about overweight and/or obesity
      include: uncertainty about appropriate language; lack of time; concerns about
      compromising mutual trust and rapport; concerns about patient readiness; concerns
      about patients' mental health and how this may be impacted by discussing a
      potentially upsetting and stigmatising topic; and lack of effective and
      individualised treatment and/or referral options. DISCUSSION: The findings
      suggest that responses to overweight and obesity need to be localised and
      tailored. Structural-level change is required to enable better responses to
      overweight and obesity, including multidisciplinary team approaches.

PMID- 29036780
TI  - Morphine use in cancer care: A survey of attitudes and perceptions in general
      practice patients.
AB  - BACKGROUND: Morphine is widely prescribed for patients with cancer, although a
      number of attitudes have been cited as barriers to its use, including fear,
      addiction and associations with death. The aim of this study was to explore the
      nature of these beliefs, and assess the extent to which these attitudes exist in
      a general practice patient population that may require morphine in the future.
      METHODS: A 30-item survey was distributed through general practices in Victoria,
      Australia. RESULTS: Of the 379 questionnaires distributed, 290 were collected
      (76.5%). Participants were predominantly neutral on questions regarding the
      effect of morphine on the duration of life. Morphine was seen to be prescribed
      responsibly (73.5%), even while most perceived its potential for addiction
      (69.7%). Participants with experience of morphine use had more negative
      perceptions regarding its efficacy. DISCUSSION: Conversations regarding morphine
      use should include a discussion about the beliefs and experiences of the
      individual, many of which may reinforce the utility of morphine.

PMID- 29036781
TI  - Transport on prescription: How can GPs contribute to the promotion of active
      transport?
AB  - BACKGROUND: Active transport (ie walking, cycling, using public transport) can
      play a part in reducing non-communicable diseases (NCDs). Very little is known
      about how general practitioners (GPs) can contribute to promoting active
      transport. We explored GPs' ideas around active transport, and potential barriers
      and facilitators to its promotion in the clinical setting. METHODS: Using a
      maximal variation sample, we conducted 10 semi-structured interviews with GPs in
      Victoria, Australia. The socioecological model informed data collection and
      analysis. RESULTS: The idea of active transport resonated with GPs. Limited
      awareness around active transport and safety concerns regarding commuter cycling
      were barriers to clinical promotion. GPs believed patients' health, cultural
      norms, socioeconomic position and access to supportive environments could
      facilitate participation. DISCUSSION: Future efforts should prioritise awareness
      of active transport among GPs. The perspectives of GPs would be valuable to
      policymakers, particularly in designing programs to mitigate inequalities around
      active transport access and use.

PMID- 29036782
TI  - Practice-based research networks.
AB  - BACKGROUND: Practice-based research networks (PBRNs) are collaborations between
      clinical practitioners and academics. PBRNs aim to foster research in general
      practice through opportunities to learn more about how to undertake and
      participate in research, and assist in translating new knowledge into practice.
      Critically, PBRNs also offer clinicians the chance to contribute to research by
      posing questions of importance to quality clinical care. OBJECTIVE: The
      objectives of this article are to describe why PRBNs are needed, the current
      situation regarding PBRNs in Australia, and why Australian general practice and
      patient outcomes could benefit from further investment in PBRNs. DISCUSSION:
      PBRNs may assist by engaging more general practitioners (GPs) in the research
      process, thereby increasing the relevance of the research questions posed to the
      outcomes of the population GPs work within. Unlike similar countries (eg UK and
      The Netherlands), Australia no longer has any funding to support the activities
      of primary-care based PBRNs.

PMID- 29036783
TI  - Isolated huge right ventricular tumor: cardiac metastasis of tongue cancer.

PMID- 29036784
TI  - Decreased expression of lncRNA VPS9D1-AS1 in gastric cancer and its clinical
      significance.
AB  - BACKGROUND: A recent study has demonstrated that the long non-coding RNA VPS9D1
      AS1 is highly expressed in colorectal cancer and predicts poor prognosis.
      However, roles of VPS9D1-AS1 in gastric cancer remained poorly understood.
      OBJECTIVE: The aim of this study is to decipher the expression of VPS9D1-AS1 in
      gastric cancer (GC) patients, so as to assess whether or not it could be used as
      a novel biomarker for prognosis in gastric cancer patients. METHODS: The
      expression of VPS9D1-AS1 was examined in cancer tissues and paired adjacent non
      tumorous tissues from 126 gastric cancer patients using qRT-PCR. Correlations
      between the expression of VPS9D1-AS1 and clinicopathological parameters and
      patients' survival were analyzed. RESULTS: VPS9D1-AS1 expression was
      downregulated in gastric cancer tissues than that in adjacent non-tumorous
      tissues (P< 0.001). VPS9D1-AS1 expression level was markedly correlated with
      tumor size and TNM stage in gastric cancer. Kaplan-Meier analysis showed low
      expression of VPS9D1-AS1 were correlated with poor overall and disease free
      survival. On multivariate analysis, the hazard ratio of VPS9D1-AS expression was
      0.30 (95% CI = 0.13-0.66, P= 0.003) for overall survival. CONCLUSIONS: Overall,
      our data suggest that downregulated VPS9D1-AS1 may be used as a novel prognosis
      predictor of gastric cancer.

PMID- 29036785
TI  - Wide-transcriptome analysis and cellularity of bone marrow CD34+/lin- cells of
      patients with chronic-phase chronic myeloid leukemia at diagnosis vs. 12 months
      of first-line nilotinib treatment.
AB  - BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative
      disorder with heterogeneous biological and clinical features. The biomolecular
      mechanisms of CML response to tyrosine-kinase inhibitors are not fully defined.
      OBJECTIVE: We undertook a gene expression profiling (GEP) study of selected bone
      marrow (BM) CD34+/lin- cells of chronic-phase CML patients at diagnosis and after
      12 months of TKI nilotinib to investigate molecular signatures characterizing
      both conditions.

PMID- 29036786
TI  - Pancreatic cancer and associated exosomes.
AB  - Pancreatic cancers with poor prognosis are highly malignant, readily metastatic
      and of immune tolerance, mainly due to delayed detection. The metastatic
      progression and immune tolerance of pancreatic cancer is greatly attributed to
      the intercellular communication. However, exosomes are deemed to be the most
      important tool of intercellular communicators. Thus, we present a review of
      pancreatic cancer and exosomes in this article. We intensively summarize the
      progress of early pancreatic cancer and the relationship of the proliferation,
      progression and metastasis of pancreatic cancer and pancreatic cancer-derived
      exosomes, and propose new ideas of the study of pancreatic cancer.

PMID- 29036787
TI  - Evaluation of serum CCL18 as a potential biomarker for ovarian cancer.
AB  - BACKGROUND: Early detection and differentiation diagnosis of a pelvic mass (PM)
      is crucial in improving the prognosis of patients with epithelial ovarian cancer
      (EOC). C-C motif chemokine ligand 18 (CCL18) was reported as a chemokine-mediated
      tumor-related inflammation that can be detected in serum and may correlate with
      cancer patients' prognosis. OBJECTIVE: We performed this study to investigate the
      relationship between CCL18 levels and clinical characteristics of EOC patients,
      and to explore their diagnostic and prognostic values. METHODS: CCL18 serum
      concentrations were detected by ELISA in 187 patients with EOC, 126 patients with
      benign PMs, and 118 healthy controls. CCL18 serum levels were analyzed in the
      context of patients' clinicopathological information, and ROC analyses were
      performed to determine the effect of CCL18 on distinguishing benign and malignant
      PMs. The ability of CCL18 to serve as an EOC biomarker was compared with CA125.
      Further survival analyses were carried out to assess the prognostic value of
      CCL18 in EOC patients. RESULTS: Mean serum CCL18 levels were elevated in benign
      PM patients and were even higher in EOC patients than in healthy controls;
      furthermore, high CCL18 expression was associated with worse International
      Federation of Gynecology and Obstetrics (FIGO) staging and predicted a poorer
      survival of the patient. When compared with CA125, although the sensitivity and
      negative predictive values (NPV) of serum CCL18 were lower, its specificity and
      positive predictive values (PPV) were higher. CONCLUSIONS: Serum CCL18 was
      elevated in patients with EOC and could serve as a new tumor biomarker, which
      also predicted a poor survival of the patient.

PMID- 29036788
TI  - Knockdown of lncRNA CCAT2 inhibits endometrial cancer cells growth and metastasis
      via sponging miR-216b.
AB  - OBJECTIVE: Colon cancer-associated transcript 2 (CCAT2), a novel lncRNA has been
      reported as an oncogene in several cancers. This study was aimed to explore
      whether CCAT2 also exerted oncogenic roles in endometrial cancer cells. MATERIALS
      AND METHODS: The expression of CCAT2 in 30 pairs of endometrial cancer and
      matched non-cancerous tissues were detected by qRT-PCR. Two endometrial cancer
      cell lines HEC-1-A and RL95-2 were used throughout this study. CCAT2 in cells was
      silenced by transfection with shRNA targeted CCAT2, then cell growth and
      metastasis were assessed by performing trypan blue staining, Transwell assay, and
      flow cytometry. Dual-luciferase reporter assay was used to detect the combination
      of miR-216b and CCAT2. Besides, the expression of miR-216b and Bcl-2 in cells
      were overexpressed or suppressed by transfection with their correspondingly
      mimic/vector or inhibitor/shRNA. qRT-PCR and western blot analysis were performed
      to detect the expression of Bcl-2 and main factors in PTEN/PI3K/AKT and mTOR
      signaling pathways. RESULTS: CCAT2 was highly expressed in endometrial cancer
      tissues when compared to non-cancerous endometrial tissues. Knockdown of CCAT2
      inhibited HEC-1-A and RL95-2 cells viability, migration, invasion, but induced
      apoptosis. CCAT2 was an endogenous sponge by competing for miR-216b, and miR-216b
      suppression alleviated CCAT2 silence-diminished cell growth and metastasis. miR
      216b negatively regulated Bcl-2 and Bcl-2 could further active PTEN/PI3K/AKT and
      mTOR signaling pathways. CONCLUSIONS: To conclude, these results demonstrated
      lncRNA CCAT2 was highly expressed in endometrial cancer tissues. Knockdown of
      CCAT2 inhibited cell growth and metastasis of endometrial cancer cells by
      sponging miR-216b.

PMID- 29036789
TI  - Protein kinase C delta-dependent regulation of Ubiquitin-proteasome system
      function in breast cancer.
AB  - Besides the crucial role of hyperinsulinemia in the development of breast cancer
      with Type 2 diabetes mellitus (T2DM), it has been shown that hyperglycemia could
      contribute to promote cancer progression. A remarkable association within
      hyperglycemia, PKCdelta and Ubiquitin-proteasome system (UPS) has been reported,
      suggesting that PKCdelta may mediate high glucose-induced UPS activation in
      breast cancer cells. Although the independent effects of PKCdelta or UPS on
      breast cancer and T2DM are increasingly supported by experimental evidence, the
      complex interactional link between PKCdelta and UPS is still unclear. Hence, we
      focus on the relationship between PKCdelta and UPS in breast cancer with T2DM. We
      hypothesize that PKCdelta may have the function to regulate the activity of UPS.
      Further, we speculate that PKCdelta combine with proteasome alpha2 promoter, that
      indicate PKCdelta regulate the function of UPS by change the composition of
      proteasome. Therefore, we surmise that PKCdelta mediated high glucose-induced UPS
      activation in breast cancer cells, and specific PKCdelta inhibitor rottlerin
      significantly suppressed elevated glucose induced the activity of UPS. We hope
      that our paper will stimulate further studies the relationship between PKCdelta
      and UPS, and a new targeted therapy and early medical intervention for PKCdelta
      could be a useful option for breast cancer cases complicated with T2DM or
      hyperglycemia.

PMID- 29036790
TI  - Predictors for the efficacy of Endostar combined with neoadjuvant chemotherapy
      for stage IIIA (N2) NSCLC.
AB  - BACKGROUND: Endostar (rh-endostatin) is a new recombinant human endostatin, which
      could inhibit cell proliferation, angiogenesis, and tumor growth. OBJECTIVE: To
      explore anti-angiogenesis short-term efficacy combined with neoadjuvant
      chemotherapy for stage IIIA (N2) non-small cell lung cancer (NSCLC), and identify
      the potential predictive factors. METHODS: We pathologically examined 26 patients
      diagnosed with stage IIIA (N2) NSCLC who received NP chemotherapy alone or
      combined with Endostar, respectively. RESULTS: Our results indicated that total
      clinical benefit rate (CBR) 87.5% and 64% (p= 0.76), respectively. The clinical
      benefit (CB) patients in the treatment group showed significant changes in
      endothelial progenitor cells (EPC), vascular endothelial growth factor (VEGF),
      blood flow (BF), permeability surface (PMS), and microvascular density (MVD)
      before and after treatment. Compared with CB patients in the control group,
      changes in EPC and MVD (only) before and after treatment were significant. The
      variation of EPC, PMS, and MVD before and after treatment in the treatment group
      showed positive correlation with tumor regression rate (TRR) and the variation of
      MVD, whereas those of EPC and PMS demonstrated positive correlations with
      variation of MVD before and after treatment. CONCLUSION: Our findings suggested
      that PMS and EPC may be used as a predictive factor for the short-term efficacy
      of the combined therapy in NSCLC.

PMID- 29036791
TI  - Globo H expression is associated with driver mutations and PD-L1 expressions in
      stage I non-small cell lung cancer.
AB  - BACKGROUND: Globo H is a tumor-associated carbohydrate antigen exclusively
      expressed in cancer cells rather than normal tissue. Globo H has been found on
      many cancers of epithelial origins, and become an attractive target for cancer
      vaccine. OBJECTIVES: We aimed to study the expression of Globo H in non-small
      cell lung cancer (NSCLC) patients, and correlated its expression with common
      driver mutations, clinical outcomes, and status of immune checkpoint, programmed
      death-ligand 1 (PD-L1). METHODS: The study enrolled 228 patients with surgically
      resected stage I NSCLC, including 139 patients with adenocarcinoma (ADC) and 89
      patients with squamous cell carcinoma (SqCC). Using immunohistochemistry, tumors
      with moderate to strong membranous staining in ? 1% tumor cells per section were
      scored as positive Globo H expression. Driver mutations including EGFR, KRAS,
      BRAF were detected by direct sequencing, while ALK, PI3KCA, FGFR1 and PD-L1
      expression was detected by immunohistochemical (IHC) staining. RESULTS: Positive
      Globo H expression was detected in 88 of the 228 (38.6%) patients. These included
      51 of 139 (36.7%) patients with ADC and 37 of 89 (41.6%) patients with SqCC.
      Positive Globo H expression was significantly associated with EGFR mutation and
      PD-L1 expression in the ADC group, and PI3KCA overexpression in the SqCC group.
      The survival analysis showed that Globo H expression was not an independent
      prognostic factor in stage I NSCLC. CONCLUSIONS: Globo H expression was
      correlated with specific driver mutations in ADC and SqCC NSCLC tumors, as well
      as PD-L1 status. Immunotherapy targeting Globo H may have potential application
      in lung cancer treatment.

PMID- 29036792
TI  - Are Helicobacter pylori highly cytotoxic genotypes and cardia gastric
      adenocarcinoma linked? Lessons from Iran.
AB  - BACKGROUND: Although the most extensive studies revealed the role of H. pylori
      VacA and CagA toxins in the development of gastric adenocarcinoma, the magnitude
      of this association and the correlations of vacA mosaicism and cagA status with
      cardia gastric adenocarcinoma (CGA) still remain controversial. OBJECTIVE: We
      aimed to examine the linkage of H. pylori highly cytotoxic genotypes to CGA in
      Iranian populations as a model. METHODS: A total of 601 Iranian patients were
      enrolled. Biopsies were cultured, genotyped, and anatomically and histologically
      classified. RESULTS: The vacA c1 genotype, but not cagA status, showed a strong
      association with the risk of both CGA and non-cardia adenocarcinoma (NCGA),
      whether the controls were non-tumors, as those with either non-atrophic gastritis
      or peptic ulcerations, (the OR (95%CI) was 14.11 (4.91-40.52) and 9.59 (4.06
      22.65), respectively) or those with NAG (the OR (95%CI) was 10.71 (3.49-32.82)
      and 8.11 (3.26-20.16), respectively). The vacA c1/cagA+ genotype was
      significantly associated with an increased risk of NCGA, whether the controls
      were non-tumors or those with NAG; the adjusted risk was 4.706 (1.41-15.67) and
      4.85 (1.42-16.51), respectively. CONCLUSIONS: The H. pylori vacA c1 genotype, but
      not cagA status, might be the first important bacterial biomarker for predicting
      the cardia adenocarcinoma risk in male patients aged ? 55 in Iran.

PMID- 29036793
TI  - Clinical relevance of early sublingual microcirculation monitoring in septic
      shock patients.
AB  - INTRODUCTION: Although microcirculation dysfunction plays unique role in septic
      shock, translation of microcirculation to clinical practices is limited by
      current semi-quantities analysis and unclear clinical relevance of
      microcirculation monitoring. Our aim was to critically evaluate the
      characteristic nature and relevant clinical important of microcirculation.
      EVIDENCE ACQUISITION: Pubmed (2000 to August 2015) were searched to identify
      observation, case-control, intervention and randomized clinical studies
      evaluating the relationship between microcirculation alterations and mortality,
      morbidity and drug responses. The STROBE and CONSORT Statement for assessment of
      the quality of included studies. EVIDENCE SYNTHESIS: We examined results from 17
      observations, 4 randomized controlled trials and one case report published
      studies. This data set comprised of 637 patients. Early septic shock is
      associated with hypoperfusion and heterogeneous microcirculation that is
      associated with hyperlactemia and metabolic acidosis. The evidence on clinical
      relevance of microcirculation is less striking, mainly due to the limited number
      of studies and problems related to the methodological protocol of the studies and
      currently semi-quantitative analysis technique. In particular the baseline and
      time course of microcirculation alteration appears to be controversial.
      CONCLUSION: There is lack of evidences of clinical importance of early
      microcirculation monitoring and mechanism of microcirculation dysfunction in
      septic shock patients. This could be due to the methodological protocol of the
      studies and currently semi-quantitative analysis technique.

PMID- 29036794
TI  - Assessing the effect of different operation techniques on postoperative duplex
      ultrasound quality after carotid endarterectomy.
AB  - BACKGROUND: Duplex ultrasound is the first choice in diagnostics and surveillance
      of stenoses of the internal carotid arteries before and even after surgery.
      Therefore, the quality of duplex ultrasound is crucial to investigate these
      vascular pathologies. OBJECTIVE: Aim of this study was the evaluation whether
      different surgical techniques affect the postoperative quality of duplex
      ultrasound. METHODS: In a time period from January to May 2015 duplex ultrasound
      of the cervical vessels was performed in 75 patients after unilateral
      endarterectomy of the internal carotid artery at our department between 2006 and
      2012. Thereby, the non-operated contralateral side served as a control. Study
      groups were defined by the surgical techniques of eversion- or
      thrombendarterectomy with patch plasty using different patch materials and/or a
      haemostatic sealant. Duplex ultrasound analysis included acoustic impedance,
      extinction of ultrasound, thickness of skin and individual anatomic aspects of
      the patients. RESULTS: Carotid endarterectomy itself reduced intravascular grey
      levels, skin thickness and increased extinction of duplex ultrasound when
      compared to the non-operated side of the neck. In contrast, neither the kind of
      chosen operative technique nor the use of different patch materials or the
      application of a haemostatic sealant showed an effect in this regards.
      CONCLUSIONS: Whereas carotid endarterectomy per se worsens the quality of
      postoperative duplex ultrasound, the different analysed surgical techniques as
      well as used patches and the application of a haemostatic sealant can be assumed
      to be equal regarding the quality of postoperative ultrasound.

PMID- 29036795
TI  - Erythrocyte deformability and hemorheological profile in multiple myeloma.
AB  - The hemorheological profile in multiple myeloma (MM) has been extensively
      studied. Our investigation regarded the behavior of whole-blood viscosity, plasma
      viscosity and erythrocyte deformability in MM. We enrolled 24 MM patients; 13 of
      them had been recently diagnosed and were at the initial stage of therapy, 6 were
      on consolidation/conservation therapy and 5 had achieved a complete remission. On
      fasting venous blood we evaluated whole-blood and plasma viscosity at high and
      low shear rates, haematocrit, the ratios between whole-blood viscosity (at high
      and low shear rate) and haematocrit*100, the ratio between plasma viscosity at
      low and high shear rate and the erythrocyte deformability examined by using laser
      diffractometry and expressed as elongation index. A significant increase in
      plasma viscosity at low shear rate and a marked decrease in haematocrit were
      observed in MM patients compared with normal controls. Also the ratio between the
      high shear rate whole-blood viscosity and haematocrit *100 and the ratio between
      the low and high shear rate plasma viscosity were significantly increased in MM
      patients. A significant decrease in erythrocyte deformability, especially at low
      shear stresses, was found. We discuss some hypotheses that might explain the
      behavior of red blood cell deformability in MM, considering that its impairment,
      in addition to the increase of plasma viscosity, can alter the microcirculatory
      flow in these patients.

PMID- 29036796
TI  - Intestinal ischemia-reperfusion leads to early systemic micro-rheological and
      multiorgan microcirculatory alterations in the rat.
AB  - BACKGROUND: Intestinal ischemia-reperfusion (I/R) is a potentially life
      threatening situation and its pathomechanism is not fully understood yet.
      OBJECTIVE: To investigate the early micro-rheological, microcirculatory and
      morphological consequences of intestinal I/R in a rat model. METHODS: CD rats
      were anesthetized and subjected to Control (n = 7) or I/R (n = 7) groups. Left
      femoral artery cannulation and median laparotomy were performed. In the I/R group
      the superior mesenteric artery was clamped for 30 minutes. Blood samples were
      taken before (Base) and after the ischemia, at the 30th, 60th and 120th minutes
      of the reperfusion (R-30, R-60, R-120). Hematological parameters, erythrocyte
      deformability and aggregation were determined. On the jejunum, the liver and the
      right kidney laser Doppler flowmetry tests were completed. At the end of
      experiment histological samples were taken. RESULTS: Hematocrit, leukocyte and
      platelet counts increased during the reperfusion. Erythrocyte deformability
      worsened versus Control. All erythrocyte aggregation index values of I/R group
      increased gradually. Intestinal microcirculatory blood flux units (BFU) did not
      recover completely after ischemia, at R-30 liver BFU values were lower, and
      kidney values decreased by R-120. Histology showed signs of I/R injury.
      CONCLUSIONS: Micro-rheological parameters may show early and significant
      deterioration during the reperfusion that might contribute further to
      microcirculatory alterations.

PMID- 29036797
TI  - Effects of venotonic drugs on the microcirculation: Comparison between Ruscus
      extract and micronized diosmine1.
AB  - BACKGROUND: Chronic venous disease of the lower limbs is a common public health
      problem worldwide with negative impact on quality of life and results with drugs
      used to treat it are sparse, probably due to lack of good experimental models.
      OBJECTIVE: In this investigation we have tested the effects of two commonly used
      venotonic substances, Ruscus extract and micronized diosmine, on the
      microcirculation in vivo. METHODS: These substances were given orally, by gavage,
      during two weeks, twice daily and observations were made using the hamster cheek
      pouch preparation. RESULTS: The drugs elicited a dose-dependent inhibition of (1)
      macromolecular permeability increase induced by histamine or ischemia followed by
      reperfusion, being the Ruscus extract more active on both and (2) leukocyte
      endothelium interaction, again being the Ruscus extract more effective in the
      inhibition of the number of adherent and rolling leukocytes. About the duration
      of the effect after the end of the treatment, both drugs had similar effects but
      Ruscus extract showed greater permanence of its effect on all observed
      parameters. CONCLUSIONS: Our results suggest that both drugs have antioxidant and
      anti-inflammatory properties being Ruscus extract more active. It should be added
      that only Ruscus extract showed a significant venular constriction.

PMID- 29036798
TI  - No effect on the short-term of a decrease in blood viscosity on insulin
      resistance.
AB  - BACKGROUND: Blood viscosity (BV) might influence glucose delivery to peripheral
      tissues and play an important role in insulin resistance and diabetes mellitus.
      However, the exact relationship between BV and insulin resistance is not yet
      clear. OBJECTIVES: Aim of the present study is to evaluate the effects of the
      acute reduction in BV on insulin resistance, in healthy male subjects. METHODS:
      Fifteen healthy male blood donors have been studied before and 48 hours after
      blood donation. Blood and plasma viscosity have been measured at 37 degrees C
      with a cone-plate viscometer. Insulin resistance has been evaluated by
      euglycemic/hyperinsulinemic clamp in eight subjects, and by iHOMA2 Index in
      further seven subjects. RESULTS: Blood viscosity was markedly reduced after blood
      donation (BV225 (cP) 4.53 +/- 0.59 vs. 4.18 +/- 0.31, p < 0.05). Insulin
      resistance was unchanged: MFFM clamp: 5.6 +/- 4.5vs. 4.4 +/- 2.2 and iHOMA2 Index
      1.2 +/- 0.6 vs. 1.2 +/- 0.5, before vs. after respectively, p = NS. Blood
      pressure and lipids were unchanged after blood donation. CONCLUSIONS: The present
      results demonstrate that acute reduction of BV in healthy male subjects does not
      change the insulin resistance, measured using both euglycemic/hyperinsulinemic
      clamp and iHOMA2 Index. Further intervention studies are needed to assess the
      effect that the reduction in BV can have in subjects with insulin resistance.

PMID- 29036799
TI  - Hemorheological parameters in Monoclonal Gammopathy of Undetermined Significance
      (MGUS).
AB  - There is scarcity of information about the hemorheological pattern in subjects
      with Monoclonal Gammopathy of Undetermined Significance (MGUS). This preliminary
      research is focused on the behaviour of whole-blood and plasma viscosity,
      haematocrit and erythrocyte deformability in the above clinical condition. We
      enrolled 21 MGUS subjects (10 women and 11 men; mean age 66.4 +/- 11.6 years). In
      fasting venous blood we examined whole-blood and plasma viscosity at high and low
      shear rates, haematocrit, the ratios between whole-blood viscosity (at high and
      low shear rate) and haematocrit * 100, the ratio between plasma viscosity at low
      and high shear rate, and the erythrocyte deformability expressed as elongation
      index. By comparing normal controls to MGUS subjects a significant increase in
      whole-blood viscosity at high shear rate and in plasma viscosity at low shear
      rate were observed. In MGUS subjects the ratios between the high and low shear
      rate blood viscosity and haematocrit * 100, as well as the ratio between the low
      and high shear rate plasma viscosity were significantly higher. In MGUS subjects
      a marked decrease in erythrocyte deformability was also observed. The alteration
      of the hemorheological profile found in these subjects might be involved in the
      pathogenesis of thromboembolic events, which occur with a high frequency in MGUS.

PMID- 29036800
TI  - Quantitative parameters of contrast-enhanced ultrasonography for assessment of
      renal pathology: A preliminary study in chronic kidney disease.
AB  - OBJECTIVE: To assess the severity of renal pathology in patients with chronic
      kidney disease (CKD) using contrast-enhanced ultrasonography (US). METHODS: 275
      patients with CKD who were proven by renal biopsy and 30 healthy adults were
      examined using conventional US and contrast-enhanced US. Ultrasonic parameters
      included renal length, cortical thickness, rise time (RT), peak intensity (PI),
      area under the time-intensity curve (AUC), wash-in slope (WIS) and time to peak
      (TTP). Based on pathological scores, CKD patients were classified into mild, and
      moderate to severe CKD groups. The logistic regression analysis and receiver
      operating characteristic (ROC) curves were used. RESULTS: PI and AUC differed
      significantly among the controls, mild and moderate to severe CKD groups (P <
      0.05). There was significant difference in PI among the different pathology types
      (P < 0.05). The multivariate logistic regression analysis showed that PI was
      associated independently with the severity of renal pathology in patients with
      CKD (P < 0.05). PI less than 13.87 dB had a certain diagnostic ability, and the
      sensitivity and specificity were 72.5% and 64.0%, respectively. CONCLUSIONS:
      Contrast-enhanced US may be useful for noninvasive assessment of the severity of
      renal pathology. PI may be potentially valuable for guiding therapy and follow-up
      in patients with CKD.

PMID- 29036801
TI  - Misinterpretation of the sublingual microcirculation during therapy with
      levosimendan.
AB  - There is increasing evidence in the literature that preoperative treatment with
      levosimendan optimizes cardiopulmonary haemodynamics in patients scheduled for
      the implantation of a Left Ventricular Assist Device (LVAD). The present case
      report describes changes in sublingual microcirculation using incident dark field
      video microscopy in a patient, who received a continuous infusion of 0.5 mg/h
      levosimendan 12 h before LVAD implantation. Despite no evident macrohaemodynamic
      or metabolic changes, there was a dramatic reduction in total vessel density and
      perfused vessel density suggesting a deterioration of microcirculation according
      to the consensus conference criteria in vessels smaller than 20 MUm in diameter.
      However, the microcirculation of all visible vessels (regardless of diameter) was
      maintained. This potential misinterpretation is explained by a levosimedan
      induced vasodilation and the subsequent reduction of the percentage of vessels
      with a diameter smaller than 20 MUm. Physicians should carefully consider this
      pitfall of applying the consensus conference criteria in vasodilator-treated
      patients.

PMID- 29036802
TI  - Pharmacosimulation of interruptions and its solution in intravenous
      administration of cangrelor.
AB  - BACKGROUND: Cangrelor is an intravenous adenosine diphosphate (ADP) P2Y12
      receptor antagonist, which has to be administered as a bolus followed by
      immediate infusion. Nevertheless, in clinical routine deviations from the correct
      practice, such as delayed infusion onset or interruptions during infusion, may
      occur. OBJECTIVE: The objective of the present study was to investigate the
      impact of administration delays on cangrelor concentration in a pharmacological
      simulation setting and to give possible solutions for the clinical practice.
      METHODS: We simulated the effects of different delays in administration of
      cangrelor in a model based on known pharmacokinetic parameters. Additionally, we
      calculated the optimal dosage of a second bolus. RESULTS: We demonstrate that
      already a short delay between the bolus and begin of infusion as well as short
      infusion interruptions considerably affect the serum concentration of cangrelor.
      Additionally, we estimate the dosage of a possible second bolus which highly
      depends on the duration of the delay. CONCLUSIONS: Our results emphasize that
      continuous administration of cangrelor is crucial to avoid the critical time
      frame of increased thrombosis risk. We suggest a strategy for dealing with
      interruptions by demonstrating that a second bolus allows to reach rapidly an
      effective but not excessive cangrelor serum concentration.

PMID- 29036803
TI  - Extracellular ATP activates eNOS and increases intracellular NO generation in Red
      Blood Cells.
AB  - BACKGROUND: It has been well documented that ATP activates NOS enzymes and causes
      increased NO production in several cell types. Although RBC known to possesses
      eNOS enzyme activity, it has not been investigated whether RBC eNOS could be
      induced by extracellular ATP. OBJECTIVE: The aim of the present study is to
      evaluate extracellular ATP mediated eNOS activation and NO production in RBC.
      METHODS: RBC packed were isolated from healthy volunteers and re-suspended in
      Hepes solution at a hematocrit of 0.01 l/l. Intracellular NO and Ca+2 levels and
      eNOS activation measured by flow cytometry in response to P2X receptor agonist,
      Bz-ATP, in the absence and presence of NOS, P2 receptors and PI3K inhibitors.
      RESULTS: P2X receptor agonist Bz-ATP found to increase intracellular NO, Ca+2 and
      serine 1177 phosphorylated eNOS levels and these responses have shown to be
      suppressed by NOS enzyme, P2 receptors and PI3K inhibitors. CONCLUSIONS: The
      results of the study clearly demonstrated extracellular ATP induced NO generation
      in RBC through intracellular Ca+2 and PI3K/Akt pathways. The mechanism we
      described here might be important at basal conditions and also in conditions with
      increased ATP release.

PMID- 29036804
TI  - Rheopheresis as a causal therapy option for systemic scleroderma (SSc).
AB  - A complex pathomechanism accounts systemic sclerosis as a form of collagenosis. A
      triad of vasculopathy, autoinflammation, and dysbalance of the fibroblast
      function can be seen as cause, as well as symptomatic appearance. Comparative
      with other collagenoses, e.g. Lupus erythematosus, vasculopathy, instead of
      autoinflammation, appears to be clinically important in systemic scleroderma. The
      fact that autoinflammation does not represent the major role in the maintenance
      of the disease is also evident by the lack of therapeutic effects of classical
      systemic immunosuppressants. Therapeutic approaches with regard to vasculopathy
      show better effects. In consideration of therapeutic options, such principles are
      therefore most important. Apheretic methods filter out plasma proteins in the
      sense of plasmapheresis. Fibrinogen as a plasma viscosity factor is predominantly
      targeted and filtered out. In addition other accompanying plasma proteins are
      also reduced. This occurs on the one hand by dilution effects and on the other by
      unspecific binding. By this mechanism, acute phase proteins such as the C
      reactive protein and various cytokines, especially interleukin-6 are reduced by
      this method. Looking more closely at these random adjunctive plasma proteins, a
      possible central role of interleukin-6 in the development and maintenance cascade
      of systemic scleroderma becomes clear.

PMID- 29036805
TI  - Determining the IgM and IgG antibodies titer against HSV1, HSV2 and CMV in the
      serum of schizophrenia patients.
AB  - Schizophrenia is a destructive clinical syndrome with diverse mental pathologies.
      Different mechanisms and factors have a role in this disease. A possible
      mechanism is that teratogenic viruses cause brain changes and results in the
      disease appearance. The schizophrenia patients were diagnosed by psychologists
      and with the consent of patients, five CC of venous blood was drawn. Than Serum
      samples were isolated and immunoglobulin M (IgM) and immunoglobulin G (IgG)
      antibodies against herpes simplex virus-1 (HSV-1), herpes simplex virus-2 (HSV-2)
      and cytomegalovirus (CMV) were quantified by ELISA sandwich kit. The Results
      showed that anti-CMV and anti-HSV1 and anti-HSV2 IgG antibodies in schizophrenia
      patients were increased significantly (p< 0.05). The increasing of the anti-HSV2
      IgM was also observed but increasing amount of the anti-HSV1 IgM was not
      statistically significant (p< 0.05). Therefore, as a result of this study CMV and
      HSV1 and HSV2 infection can probably intensify the symptoms in schizophrenia
      patients.

PMID- 29036806
TI  - Pritumumab, the first therapeutic antibody for glioma patients.
AB  - Immunotherapy is now at the forefront of cancer therapeutic development. Gliomas
      are a particularly aggressive form of brain cancer for which immunotherapy may
      hold promise. Pritumumab (also known in the literature as CLNH11, CLN-IgG, and
      ACA-11) was the first monoclonal antibody tested in cancer patients. Pritumumab
      is a natural human monoclonal antibody developed from a B lymphocyte isolated
      from a regional draining lymph node of a patient with cervical carcinoma. The
      antibody binds ecto-domain vimentin on the surface of cancer cells. Pritumumab
      was originally tested in clinical trials with brain cancer patients in Japan
      where it demonstrated therapeutic benefit. It was reported to be a safe and
      effective therapy for brain cancer patients at doses 5-10 fold less than
      currently approved antibodies. Phase I dose escalation clinical trials are now
      being planned with pritumumab for the near future. Here we review data on the
      development and characterization of pritumumab, and review clinical trails data
      assessing immunotherapeutic effects of pritumumab for glioma patients.

PMID- 29036807
TI  - Obtaining and characterization of monoclonal antibodies against recombinant
      extracellular domain of human epidermal growth factor receptor 2.
AB  - Human epidermal growth factor receptor 2 (HER2) is an important biomarker for
      detection and treatment of different types of cancers such as breast, ovarian,
      stomach cancer. In this study, we developed a monoclonal antibody against the
      extracellular domain (ECD) of HER2 biomarker of breast cancer. For this purpose,
      the ECD-HER2 gene was amplified and cloned into an expression vector. Gene was
      generated in Escherichia coli BL21 (DE3) strain for expression of recombinant
      protein. The expressed protein was separated by SDS-PAGE and detected by anti-his
      monoclonal antibody in immunoblotting. Hybridoma cells were obtained by fusing
      myeloma cells with mouse spleen cells injected with recombinant ECD-HER2 and
      screened by ELISA for the production of monoclonal antibody. The results indicate
      that out of three candidate hybridoma cells one clone (1E7) was producing the
      highest titer and antibody specificity was envisioned in ELISA results. In vivo
      scaling up culture of hybridoma cells in BALB/C mice lead to significant increase
      in the monoclonal antibody concentration up to 16 mg/ml. Immunochemical methods
      demonstrated the specificity of developed antibody against ECD-HER2 protein.

PMID- 29036808
TI  - Ecotropic Viral Integration Site 5 (EVI5) expression analysis in multiple
      sclerosis patients.
AB  - BACKGROUND: Multiple sclerosis (MS) is a complex immune-related disorder of the
      central nervous system (CNS) in which dysregulation of different classes of T
      cells are involved. Variants in Ecotropic Viral Integration Site 5 (EVI5) gene
      has been shown to be significantly associated with MS in different populations.
      OBJECTIVES: However, there is no data regarding relative expression of this gene
      in peripheral blood of MS patients compared with healthy controls. METHODS: In
      the present study we assessed expression of EVI5 in 50 Iranian MS patients
      compared with healthy subjects by means of quantitative real time RT-PCR.
      RESULTS: Statistical analyses showed no significant difference in EVI5 relative
      expression neither between total MS patients and healthy controls nor between age
      and sex-based subgroups of patients and controls except for a trend toward
      significance in patients aged between 30 and 40 years compared with healthy
      subjects in both sexes (P= 0.068 and 0.075 for males and females respectively).
      No significant correlation was found between the expression level of this gene
      and disease duration, age at onset or Expanded Disability Status Scale (EDSS).
      CONCLUSION: Future studies are needed to explore the role of EVI5 in the
      pathogenesis of MS.

PMID- 29036810
TI  - Neutralizing activity and safety of human monoclonal antibodies against hepatitis
      C virus.
AB  - AIM: Assessment of the neutralizing activity of human monoclonal antibodies
      against HCV and also study their safety in experimental small animals (Swiss
      mice). MATERIALS AND METHODS: Assessment of neutralizing activity of human
      monoclonal antibodies against HCV envelope regions (E1, E2) by two methods: by
      HCV cc infectious system 1) and by using positive HCV positive serum as source of
      HCV particles genotype 4a (neutralizing assay 2). Dot ELISA was used to study the
      activity of the generated antibodies. Safety and toxicity of the generated human
      antibodies were tested by assessing the changes in the biochemistry of liver
      function and kidney function tests, Complete blood counts (CBC) and studying the
      pathological changes with different concentrations of purified human antibodies
      were carried out.. RESULTS: Human Abs # 5 & 11 showed neutralizing activity by
      (neutralizing assay 2) but were not neutralizing by HCV cc assay. Human Abs # 12
      & 15 showed neutralizing activity by the two methods i.e our generated human
      antibodies Abs# 5 &11 & 12 & 15 were neutralizing for HCV genotype 4a and Abs #
      12 & 15 were neutralizing for HCV genotypes 4a and 2a. Liver and kidney functions
      and CBC results indicated that doses of 10 MUg, 100 MUg were safe. The
      histopathological results indicated that the dose of 10 MUg of purified human
      monoclonal antibodies per mouse body weight was safe. CONCLUSION: The generated
      human monoclonal antibodies can be used to develop potent immunotherapy agents
      that can be administrated for the post-transplantation patients to prevent the
      recurrence of HCV infection. Also, the monoclonal antibodies can be used to
      develop a candidate vaccine against HCV.

PMID- 29036809
TI  - Role of FSHR rs6165 and ESR2 rs4986938 polymorphisms in ovarian stimulation of
      Iranian women who underwent assisted reproduction treatment.
AB  - BACKGROUND: Gonadotropin therapy was used to stimulate the ovary in infertile
      women who underwent assisted reproduction treatment (ART). Numerous studies
      indicated that infertile women showed different responses to gonadotropin
      therapy. Follicle stimulating hormone receptor (FSHR) and Oestrogen receptor (ER)
      polymorphisms have been reported to involve induction of folliculogenesis and
      ovarian response to treatment. METHODS: In the present study, two polymorphisms,
      namely FSHR rs6165 and ESR2 rs4986938, were investigated in 198 Iranian infertile
      women aged less than 39 years who underwent ART. After DNA extraction, these
      polymorphisms were genotyped by TaqMan genotyping assay. According to the number
      of eggs released during ovulation, the patients were categorized into poor
      responders (PR) and good responders (GR). The results indicated that the good
      responders showed lower levels of FSH and LH than poor responders. RESULTS: No
      association was observed between ESR2 rs4986938 and poor response in Iranian
      women patients. Instead, FSHR rs6165 showed a strong association with ovarian
      response to ART (p< 0.05). CONCLUSION: The obtained results indicated that FSHR
      rs6165, not ESR2 rs4986938, could be suggested as a candidate marker to predict
      poor ovarian response.

PMID- 29036812
TI  - Altered Gut Microbiota in a Mouse Model of Alzheimer's Disease.
AB  - The topic of gut microbiota is currently attracting considerable interest as a
      potential factor in Alzheimer's disease (AD). However, the extent and time course
      of alterations in the gut microbiota, and their effects on AD pathology remain
      uncertain. Herein, we compared the fecal microbiomes and fecal short chain fatty
      acid composition (SCFAs) between wild-type and AD model mice at different ages
      under strictly controlled specific pathogen free conditions, and also conducted
      microscopic investigations of intestinal structures. Our results showed that the
      microbiota composition and diversity were perturbed and the level of SCFAs was
      reduced in AD mice, predicting alterations in more than 30 metabolic pathways,
      which may be associated with amyloid deposition and ultrastructural abnormalities
      in AD mouse intestine. These findings indicate that AD pathology might not only
      affect brain function directly, but also exacerbate cognitive deficits through
      reducing the level of SCFAs via alterations of gut microbiota induced by
      intestinal amyloid deposition. Our data may support a role of gut microbiota, and
      suggest a novel route for therapeutic intervention in AD.

PMID- 29036811
TI  - Sildenafil Improves Vascular and Metabolic Function in Patients with Alzheimer's
      Disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is the leading cause of degenerative
      dementia in the aging population. Patients with AD have alterations in cerebral
      hemodynamic function including reduced cerebral blood flow (CBF) and cerebral
      metabolic rate. Therefore, improved cerebrovascular function may be an attractive
      goal for pharmaceutical intervention in AD. OBJECTIVE: We wished to observe the
      acute effects of sildenafil on cerebrovascular function and brain metabolism in
      patients with AD. METHODS: We used several novel non-invasive MRI techniques to
      investigate the alterations of CBF, cerebral metabolic rate of oxygen (CMRO2),
      and cerebrovascular reactivity (CVR) after a single dose of sildenafil
      administration in order to assess its physiological effects in patients with AD.
      CBF, CMRO2, and CVR measurements using MRI were performed before and one hour
      after the oral administration of 50 mg sildenafil. Baseline Montreal Cognitive
      Assessment score was also obtained. RESULTS: Complete CBF and CMRO2 data were
      obtained in twelve patients. Complete CVR data were obtained in eight patients.
      Global CBF and CMRO2 significantly increased (p = 0.03, p = 0.05, respectively)
      following sildenafil administration. Voxel-wise analyses of CBF maps showed that
      increased CBF was most pronounced in the bilateral medial temporal lobes. CVR
      significantly decreased after administration of sildenafil. CONCLUSION: Our data
      suggest that a single dose of sildenafil improves cerebral hemodynamic function
      and increases cerebral oxygen metabolism in patients with AD.

PMID- 29036813
TI  - Association Between Later Life Lifestyle Factors and Alzheimer's Disease
      Biomarkers in Non-Demented Individuals: A Longitudinal Descriptive Cohort Study.
AB  - BACKGROUND: Lifestyle factors have been associated with the risk of dementia, but
      the association with Alzheimer's disease (AD) remains unclear. OBJECTIVE: To
      examine the association between later life lifestyle factors and AD biomarkers
      (i.e., amyloid-beta 1-42 (Abeta42) and tau in cerebrospinal fluid (CSF), and
      hippocampal volume) in individuals with subjective cognitive decline (SCD) and
      mild cognitive impairment (MCI). In addition, to examine the effect of later life
      lifestyle factors on developing AD-type dementia in individuals with MCI.
      METHODS: We selected individuals with SCD (n = 111) and MCI (n = 353) from the
      DESCRIPA and Kuopio Longitudinal MCI studies. CSF Abeta42 and tau concentrations
      were assessed with ELISA assay and hippocampal volume with multi-atlas
      segmentation. Lifestyle was assessed by clinical interview at baseline for:
      social activity, physical activity, cognitive activity, smoking, alcohol
      consumption, and sleep. We performed logistic and Cox regression analyses
      adjusted for study site, age, gender, education, and diagnosis. Prediction for AD
      type dementia was performed in individuals with MCI only. RESULTS: Later life
      lifestyle factors were not associated with AD biomarkers or with conversion to AD
      type dementia. AD biomarkers were strongly associated with conversion to AD-type
      dementia, but these relations were not modulated by lifestyle factors.
      Apolipoprotein E (APOE) genotype did not influence the results. CONCLUSIONS:
      Later life lifestyle factors had no impact on key AD biomarkers in individuals
      with SCD and MCI or on conversion to AD-type dementia in MCI.

PMID- 29036814
TI  - Curcumin Ameliorates Neuroinflammation, Neurodegeneration, and Memory Deficits in
      p25 Transgenic Mouse Model that Bears Hallmarks of Alzheimer's Disease.
AB  - Several studies have indicated that neuroinflammation is indeed associated with
      neurodegenerative disease pathology. However, failures of recent clinical trials
      of anti-inflammatory agents in neurodegenerative disorders have emphasized the
      need to better understand the complexity of the neuroinflammatory process in
      order to unravel its link with neurodegeneration. Deregulation of Cyclin
      dependent kinase 5 (Cdk5) activity by production of its hyperactivator p25 is
      involved in the formation of tau and amyloid pathology reminiscent of Alzheimer's
      disease (AD). Recent studies show an association between p25/Cdk5 hyperactivation
      and robust neuroinflammation. In addition, we recently reported the novel link
      between the p25/Cdk5 hyperactivation-induced inflammatory responses and
      neurodegenerative changes using a transgenic mouse that overexpresses p25
      (p25Tg). In this study, we aimed to understand the effects of early intervention
      with a potent natural anti-inflammatory agent, curcumin, on p25-mediated
      neuroinflammation and the progression of neurodegeneration in p25Tg mice. The
      results from this study showed that curcumin effectively counteracted the p25
      mediated glial activation and pro-inflammatory chemokines/cytokines production in
      p25Tg mice. Moreover, this curcumin-mediated suppression of neuroinflammation
      reduced the progression of p25-induced tau/amyloid pathology and in turn
      ameliorated the p25-induced cognitive impairments. It is widely acknowledged that
      to treat AD, one must target the early-stage of pathological changes to protect
      neurons from irreversible damage. In line with this, our results demonstrated
      that early intervention of inflammation could reduce the progression of AD-like
      pathological outcomes. Moreover, our data provide a rationale for the potential
      use of curcuminoids in the treatment of inflammation associated neurodegenerative
      diseases.

PMID- 29036815
TI  - Diaschisis-Like Association of Hippocampal Atrophy and Posterior Cingulate Cortex
      Hypometabolism in Cognitively Normal Elderly Depends on Impaired Integrity of
      Parahippocampal Cingulum Fibers.
AB  - Hippocampal atrophy and hypometabolism of the posterior cingulate cortex (PCC),
      early markers of Alzheimer's disease (AD), have been shown to be associated in
      late mild cognitive impairment and early AD via atrophy of connecting cingulum
      fibers. Recently, a direct association of hippocampal atrophy and PCC
      hypometabolism has been shown in cognitively normal elderly. We aimed to
      investigate if this association might be modulated by partly non-hippocampogenic
      alterations of parahippocampal cingulum (PHC) integrity. 45 cognitively healthy
      elderly aged 59 to 89 years were included from the Alzheimer's Disease
      Neuroimaging Initiative. Hippocampal volumes and PCC glucose metabolism were
      measured using MRI and FDG-PET. PHC fibers connecting the hippocampus and the PCC
      were reconstructed using diffusion weighted MRI and measures of diffusivity were
      calculated. Using robust linear regression, interaction effects of PHC
      diffusivity and hippocampal volume on PCC metabolism were calculated. For both
      hemispheres, significant interaction effects were found for PHC mean diffusivity.
      Interaction effects were such that the association of hippocampal volume and PCC
      metabolism was higher in subjects with increased mean diffusivity in PHC fibers.
      In cognitively normal elderly, compromised integrity of the PHC may increase the
      risk of PCC hypometabolism due to hippocampal atrophy. Spared PHC fiber integrity
      may protect against PCC hypometabolism due to hippocampal atrophy.

PMID- 29036816
TI  - Sex Difference in Aerobic Exercise Efficacy to Improve Cognition in Older Adults
      with Vascular Cognitive Impairment: Secondary Analysis of a Randomized Controlled
      Trial.
AB  - Aerobic training (AT) is a promising, non-pharmacological intervention to
      mitigate the deleterious effects of aging and disease on brain health. However, a
      large amount of variation exists in its efficacy. This is a secondary analysis of
      a randomized controlled trial of AT in 71 older adults with subcortical ischemic
      vascular cognitive impairment (NCT01027858). Specifically, we investigated: 1)
      whether sex moderates the relationship between AT and executive functions, and 2)
      the role of brain derived neurotrophic factor (BDNF) and gains in functional
      fitness capacity. Older adults were randomly assigned to either 6-month, thrice
      weekly AT or to usual care plus education (CON). At baseline, trial completion,
      and 6-month follow-up, executive functions were assessed with the Trail Making
      Test (A & B), verbal digits forward and backward test, and the Stroop Test.
      Functional fitness capacity was assessed with the 6-Minute Walk Test. Compared
      with CON, AT significantly improved Trail Making Test performance in females but
      not males, an effect that was retained at follow-up. AT significantly increased
      BDNF levels in females but decreased levels in males. On the other hand, AT led
      to significant gains in functional fitness capacity in males only. This study
      provides evidence that sex differences exist in AT efficacy on brain health as
      well as in the biological mechanisms subserving AT.

PMID- 29036817
TI  - Initial Heart Rate Reactivity to Socioemotional Pictures in Early-Onset
      Alzheimer's Disease.
AB  - Patients with Alzheimer's disease (AD) often have generalized anxiety,
      particularly in early-onset AD (EOAD) or the first stages of their disease. This
      increased anxiety could be associated with decreased sensorimotor gating with
      increased attention to significant stimuli from AD pathology in the entorhinal
      cortex. We investigated whether widening initial attention to socioemotional
      stimuli was association with anxiety among 16 patients with first stage EOAD
      compared to 19 normal controls (NCs). The participants underwent assessment of
      their initial heart rate deceleration ("orienting response"; OR), a measure of
      attentional refocusing, to pictures (International Affective Picture Stimuli)
      varying in pleasant-unpleasant valence and social-nonsocial content. The results
      showed group differences; the EOAD patients had significantly larger ORs than the
      NCs across conditions, with larger ORs in each valence and social condition. In
      addition, the EOAD patients, but not the NCs, showed ORs to normally less
      threatening stimuli, particularly pleasant, but also less significantly, social
      stimuli. On the Neuropsychiatric Inventory, the ORs among the EOAD patients
      significantly correlated with anxiety scores. Together, these findings suggest
      that anxiety in mild EOAD may be associated with widening attentional refocusing
      to socioemotional stimuli, possibly reflecting decreased sensorimotor gating in
      the entorhinal cortex. This finding could be a potential biomarker for the first
      stages of AD.

PMID- 29036818
TI  - A 9-microRNA Signature in Serum Serves as a Noninvasive Biomarker in Early
      Diagnosis of Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is the most common type of age-related neurodegenerative
      disorder; nevertheless, nowadays there are no reliable biomarkers or non-invasive
      techniques available for its early detection. Recent studies have indicated that
      the circulating level profiles of microRNAs (miRNAs) have the potential to be
      used as valuable biomarkers for diagnosis, staging, and progress monitoring of
      various diseases. Here we report a novel 9-miRNA signature (hsa-miR-26a-5p, hsa
      miR-181c-3p, hsa-miR-126-5p, hsa-miR-22-3p, hsa-miR-148b-5p, hsa-miR-106b-3p, hsa
      miR-6119-5p, hsa-miR-1246, and hsa-miR-660-5p) that can be utilized as biomarker
      for detecting AD. We respectively profiled the serum miRNAs from 19 AD patients
      and 9 healthy control (HC) participants using the Next-Generation Sequencing
      (NGS). The NGS results were validated by quantitative real-time polymerase chain
      reaction (qRT-PCR) on a larger cohort of 121 AD and 86 HC cases. All the patients
      were divided into three groups (mild, moderate, and severe AD) based on the Mini
      Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). Our research
      indicates that abnormal expression of distinct serum miRNAs occurs at different
      stages of AD. The difference of the area under the receiver operator
      characteristics curve (AUC) between the AD and the HC is between 70% and 85%.
      Among the 9 miRNAs, hsa-miR-22-3p has the best sensitivity (81.8%) and
      specificity (70.9%). The miRNA-panel is more valuable for AD diagnosis. The data
      suggest that the differentially expressed serum miRNAs could be used as
      biomarkers to improve the diagnosis of AD, particularly at the early stage, and
      to classify its clinical stages.

PMID- 29036819
TI  - Age and Graphomotor Decision Making Assessed with the Digital Clock Drawing Test:
      The Framingham Heart Study.
AB  - BACKGROUND: Digital Clock Drawing Test (dCDT) technology enables the examination
      of detailed neurocognitive behavior as behavior unfolds in real time; a
      capability that cannot be obtained using a traditional pen and paper testing
      format. OBJECTIVE: Parameters obtained from the dCDT were used to investigate
      neurocognitive constructs related to higher-order neurocognitive decision making
      and information processing speed. The current research sought to determine the
      effect of age as related to combined motor and non-motor components of drawing,
      and higher-order decision making latencies. METHODS: A large group of stroke- and
      dementia- free Framingham Heart Study participants were administered the dCDT to
      command and copy with hands set for "10 after 11". Six age groups (age range 28
      98) were constructed. RESULTS: Differences between age groups were found for
      total time to completion, total pen stroke count, and higher-order decision
      making latencies in both command and copy test conditions. CONCLUSION: Longer age
      related decision making latencies may reflect a greater need for working memory
      and increased self-monitoring in older subjects. These latency measures have
      potential to serve as neurocognitive biomarkers of Alzheimer's disease and other
      insidious neurodegenerative disorders.

PMID- 29036820
TI  - Job Loss After Diagnosis of Early-Onset Dementia: A Matched Cohort Study.
AB  - Early-onset dementia (EOD) affects the employment of patients and family members.
      To demonstrate how likely employees are to leave their jobs after an EOD
      diagnosis for themselves or a family member, we conducted a matched cohort study
      of 143 employees and 77 family members diagnosed with EOD using a claims
      database. We matched these participants to 5 controls each, and followed them for
      approximately 600 days. In the employee cohort, patients with EOD were more
      likely to leave their jobs than were controls (hazard ratio: 2.26). This suggests
      that healthcare providers should offer employment support to patients just after
      diagnosis.

PMID- 29036821
TI  - Estimated Glomerular Filtration Rate is not Associated with Alzheimer's Disease
      in a Northern Ireland Cohort.
AB  - BACKGROUND: Alzheimer's disease (AD) prevalence is increasing globally and
      typically progresses for several years prior to clinical presentation of
      dementia. Renal dysfunction and vascular disease have been reported in
      association with dementia in several cross-sectional and longitudinal studies,
      and may contribute to AD risk. Experimental and observational studies suggest
      amyloid-beta (Abeta) clearance may be impaired in chronic kidney disease (CKD)
      indicating a mechanism for increased AD risk. OBJECTIVE: The objective of this
      study was to compare estimated glomerular filtration rate (eGFR) between
      individuals with AD and cognitively intact controls, controlling for potential
      confounding factors. METHODS: A cross-sectional, case-control study was carried
      out in 317 cognitively normal participants and 253 cases with a clinical
      diagnosis of AD in a UK tertiary care dementia clinic. Associations were
      considered using logistic regression adjusting for confounding variables (age,
      APOEE4 genotype, systolic blood pressure, education (left school at 14), and
      smoking status). RESULTS: AD cases were older than cognitively intact controls,
      had lower MMSE scores, were more likely to have at least one APOEE4 allele, had
      higher rates of smoking, were more likely to be taking aspirin and/or
      clopidogrel, and had lower blood pressure. We found no significant association
      between eGFR and AD both before and following adjustment for appropriate
      confounders. CONCLUSION: This study failed to find an association between eGFR
      and AD in a cross-sectional sample study of elderly white individuals.

PMID- 29036822
TI  - Cortical Cerebral Microinfarcts on 3 Tesla MRI in Patients with Vascular
      Cognitive Impairment.
AB  - BACKGROUND: Cerebral microinfarcts (CMIs) are small ischemic lesions that are a
      common neuropathological finding in patients with stroke or dementia. CMIs in the
      cortex can now be detected in vivo on 3 Tesla MRI. OBJECTIVE: To determine the
      occurrence of CMIs and associated clinical features in patients with possible
      vascular cognitive impairment (VCI). METHOD: 182 memory-clinic patients (mean age
      71.4+/-10.6, 55% male) with vascular injury on brain MRI (i.e., possible VCI)
      underwent a standardized work-up including 3 Tesla MRI and cognitive assessment.
      A control group consisted of 70 cognitively normal subjects (mean age 70.6+/-4.7,
      60% male). Cortical CMIs and other neuroimaging markers of vascular brain injury
      were rated according to established criteria. RESULT: Occurrence of CMIs was
      higher (20%) in patients compared to controls (10%). Among patients, the presence
      of CMIs was associated with male sex, history of stroke, infarcts, and white
      matter hyperintensities. CMI presence was also associated with a diagnosis of
      vascular dementia and reduced performance in multiple cognitive domains.
      CONCLUSION: CMIs on 3 Tesla MRI are common in patients with possible VCI and co
      occur with imaging markers of small and large vessel disease, likely reflecting a
      heterogeneous etiology. CMIs are associated with worse cognitive performance,
      independent of other markers of vascular brain injury.

PMID- 29036823
TI  - Prevalence and Correlates of Behavioral Disorders in Old Age Subjects with
      Cognitive Impairment: Results from the ReGAl Project.
AB  - BACKGROUND: Presence of behavioral and psychological symptoms of dementia (BPSD)
      is very common in subjects with cognitive impairment, representing an important
      determinant of disease progression, institutionalization, and worse prognosis.
      Knowledge of the prevalence and correlates of BPSD in community-living old
      subjects with cognitive impairment is limited so far, but it is essential for
      establishing specifically tailored care and cure in such a vulnerable population.
      OBJECTIVE: With this study, we aimed at investigating, in a large sample of old
      age subjects with cognitive impairment, BPSD prevalence and correlates including
      the main demographic, clinical, and socio-environmental characteristics. METHODS:
      Data were gathered from the ReGAl project (Rete Geriatrica Alzheimer; Geriatric
      Network on Alzheimer's disease), a large longitudinal Italian multicentric
      clinical-based study, promoted by the Italian Society of Gerontology and
      Geriatrics (SIGG). RESULTS: We evaluated data from 4,157 old-age subjects
      affected by mild cognitive impairment (MCI) (541; 13%) or dementia (3616; 87%).
      85.2% of all the population presented with at least one BPSD. Using a factor
      analysis, we identified four factors of BPSD: psychotic, affective, maniac, and
      impulse control behaviors. Logistic regression analyses revealed that among the
      main demographic, clinical, and socio-environmental aspects considered, only
      comorbidity was associated with all factors, independently of multiple
      covariates. CONCLUSION: Identification of BPSD is crucial in everyday clinical
      practice and necessary to develop specific interventions and to define
      appropriate outcomes in their management. BPSD occur in a complex
      psychopathological context, influenced by several demographic and environmental
      factors that must be taken into account for a correct diagnosis and treatment.

PMID- 29036825
TI  - The Emergence of a New Conceptual Framework for Alzheimer's Disease.
AB  - The New Criteria for the diagnosis of Alzheimer's disease (AD), published by a
      group of experts in 2007, have resulted in a revolution in the comprehension of
      the disease. Before 2007, the diagnosis of AD dementia was done through a process
      of exclusion: it was considered in the case of patients with a dementia syndrome
      without identified etiologies. This traditional algorithm had three major
      limitations that penalize the disease: 1) a low accuracy of the performance which
      may share responsibility for negative results in clinical trials; 2) a late
      identification of the patients only when they reach the threshold of dementia
      which may delay the activation of optimal care; and last but not least, 3) an
      absence of clear recognition of AD as a disease because of the lack of specific
      arguments for its identification. Since 2007, the disease has gained a clear
      definition based on positive evidence: a specific clinical phenotype (the
      amnestic syndrome of the hippocampal type) and the presence of biomarkers,
      considered as a biological signature of the disease. Thanks to these positive
      arguments, AD is a clinically and biologically well-delineated disease, no longer
      defined as "probable". It is now possible to certify that a given patient has or
      does not have the disease. Like diabetes, cancer, hyperthyroidism or any other
      disorder, AD has now a clear definition with well-defined borders. The disease
      has entered the world of medicine with identified diseases with a biological
      fingerprint. This is the story of this adventure that we will present now.

PMID- 29036824
TI  - Alzheimer's Disease Biomarkers and Future Decline in Cognitive Normal Older
      Adults.
AB  - BACKGROUND: Identifying older adults at risk of cognitive decline represents a
      challenge as Alzheimer's disease (AD) modifying therapies move toward preclinical
      stages. OBJECTIVE: To investigate the relationship between AD biomarkers and
      subsequent change in cognition in a cohort of cognitively intact older adults.
      METHODS: 84 cognitively normal subjects (mean age 72.0 years, 59% women) were
      recruited through the Massachusetts Alzheimer's Disease Research Center and the
      Harvard Aging Brain Study and followed over 3 years. Measurements of amyloid-beta
      1-42 (Abeta42), total Tau (t-Tau), and Tau phosphorylated at threonine 181 (p
      Tau181) in the cerebrospinal fluid (CSF) at study entry were available in all
      cases. Baseline brain MRI, FDG-PET, and PiB-PET data were available in the
      majority of participants. Relationship between baseline AD biomarkers and
      longitudinal change in cognition was assessed using Cox proportional hazard
      regression and linear mixed models. RESULTS: 14% participants increased their
      global Clinical Dementia Rating (CDR) score from 0 to 0.5 during follow-up. A CDR
      score increase was associated with higher baseline CSF t-Tau and p-Tau181, higher
      global cortical PiB retention, and lower hippocampal volume. The combination of
      high CSF t-Tau and low Abeta42 or low hippocampal volume was more strongly
      related to cognitive outcome than each single biomarker. Higher CSF t-Tau was the
      only biomarker associated with subsequent decline in MMSE score. CONCLUSIONS:
      Baseline CSF t-Tau and p-Tau181, in vivo amyloid load, and hippocampal volume
      were all independently associated with future decline in cognition. The
      discriminatory ability of these biomarkers to predict risk of cognitive decline,
      however, was only modest.

PMID- 29036826
TI  - What Can Quantitative Gait Analysis Tell Us about Dementia and Its Subtypes? A
      Structured Review.
AB  - Distinguishing dementia subtypes can be difficult due to similarities in clinical
      presentation. There is increasing interest in discrete gait characteristics as
      markers to aid diagnostic algorithms in dementia. This structured review explores
      the differences in quantitative gait characteristics between dementia and healthy
      controls, and between four dementia subtypes under single-task conditions:
      Alzheimer's disease (AD), dementia with Lewy bodies and Parkinson's disease
      dementia, and vascular dementia. Twenty-six papers out of an initial 5,211 were
      reviewed and interpreted using a validated model of gait. Dementia was associated
      with gait characteristics grouped by slower pace, impaired rhythm, and increased
      variability compared to normal aging. Only four studies compared two or more
      dementia subtypes. People with AD are less impaired in pace, rhythm, and
      variability domains of gait compared to non-AD dementias. Results demonstrate the
      potential of gait as a clinical marker to discriminate between dementia subtypes.
      Larger studies using a more comprehensive battery of gait characteristics and
      better characterized dementia sub-types are required.

PMID- 29036827
TI  - Validation by Magnetic Resonance Imaging of the Diagnostic Potential of a
      Heptapeptide-Functionalized Imaging Probe Targeted to Amyloid-beta and Able to
      Cross the Blood-Brain Barrier.
AB  - The diagnosis of Alzheimer's disease (AD) is a critical step in the management of
      patients. We have developed a non-invasive diagnosis tool based on magnetic
      resonance molecular imaging (MRMI) of amyloid-beta peptide using ultra-small
      particles of iron oxide (USPIO) functionalized with a disulfide constrained
      cyclic heptapeptide (PHO) identified by phage display (USPIO-PHO). After
      previously demonstrating the optimal pharmacologic properties of USPIO-PHO and
      its capacity to cross the blood-brain barrier (BBB), the ability of USPIO-PHO to
      target amyloid plaques (AP) by MRMI has been validated in the present work on AD
      transgenic mice. The immunohistochemistry and immunofluorescent detection of
      USPIO-PHO on brain sections collected after in vivo MRMI studies enabled its
      colocalization with AP, confirming the BBB passage and specific targeting. The AP
      targeting by USPIO-PHO has been moreover corroborated by the good correlation
      between the number of AP detected with anti-amyloid beta antibody and Perls'-DAB
      staining. Finally, the crossing mechanism of USPIO-PHO through the BBB was
      elucidated, revealing the involvement of non-degradation pathway of caveolae,
      while the control contrast agent USPIO-PEG was not endocytosed by the human brain
      endothelial cells.

PMID- 29036829
TI  - microRNA 221 Targets ADAM10 mRNA and is Downregulated in Alzheimer's Disease.
AB  - ADAM10 is the alpha-secretase that cleaves amyloid-beta protein precursor in the
      non-amyloidogenic pathway in Alzheimer's disease (AD) and is known to be
      regulated by different microRNAs (miRNAs), which are post-transcriptional
      regulators related to several biological and pathological processes, including
      AD. Here we proposed to explore and validate miRNAs that have direct or indirect
      relations to the AD pathophysiology and ADAM10 gene. Approximately 700 miRNAs
      were analyzed and 21 differentially expressed miRNAs were validated in a sample
      of 21 AD subjects and 17 cognitively healthy matched controls. SH-SY5Y cells were
      transfected with miR-144-5p, miR-221, and miR-374 mimics and inhibitors, and
      ADAM10 protein levels were evaluated. miR-144-5p, miR-221, and miR-374 were
      downregulated in AD. The overexpression of miR-221 in SH-SY5Y cells resulted in
      ADAM10 reduction and its inhibition in ADAM10 increased. These findings show that
      miR-221 can be a new potential therapeutic target for increasing ADAM10 levels in
      AD. In addition, these results can contribute to the better understanding of
      ADAM10 post-transcriptional regulation.

PMID- 29036830
TI  - Our Working Point of View of Tau Protein.
AB  - Tau protein, which was discovered in Prof. Kirschner's laboratory in 1975, has
      been the focus of my research over the last 40 years. In this issue of the
      Journal of Alzheimer's Disease commemorating its 20th year of publication, I will
      provide a short review of some of the features of my relationship with tau.

PMID- 29036828
TI  - Mitochondria and Mitochondrial Cascades in Alzheimer's Disease.
AB  - Decades of research indicate mitochondria from Alzheimer's disease (AD) patients
      differ from those of non-AD individuals. Initial studies revealed structural
      differences, and subsequent studies showed functional deficits. Observations of
      structure and function changes prompted investigators to consider the
      consequences, significance, and causes of AD-related mitochondrial dysfunction.
      Currently, extensive research argues mitochondria may mediate, drive, or
      contribute to a variety of AD pathologies. The perceived significance of these
      mitochondrial changes continues to grow, and many currently believe AD
      mitochondrial dysfunction represents a reasonable therapeutic target. Debate
      continues over the origin of AD mitochondrial changes. Some argue amyloid-beta
      (Abeta) induces AD mitochondrial dysfunction, a view that does not challenge the
      amyloid cascade hypothesis and that may in fact help explain that hypothesis.
      Alternatively, data indicate mitochondrial dysfunction exists independent of
      Abeta, potentially lies upstream of Abeta deposition, and suggest a primary
      mitochondrial cascade hypothesis that assumes mitochondrial pathology
      hierarchically supersedes Abeta pathology. Mitochondria, therefore, appear at
      least to mediate or possibly even initiate pathologic molecular cascades in AD.
      This review considers studies and data that inform this area of AD research.

PMID- 29036831
TI  - Dementia Pugilistica Revisited.
AB  - Extensive exposure of boxers to neurotrauma in the early 20th century led to the
      so-called punch drunk syndrome, which was formally recognized in the medical
      literature in 1928. "Punch drunk" terminology was replaced by the less derisive
      'dementia pugilistica' in 1937. In the early case material, the diagnosis of
      dementia pugilistica required neurological deficits, including slurring
      dysarthria, ataxia, pyramidal signs, extrapyramidal signs, memory impairment, and
      personality changes, although the specific clinical substrate has assumed lesser
      importance in recent years with a shift in focus on molecular pathogenesis. The
      postmortem neuropathology of dementia pugilistica has also evolved substantially
      over the past 90 years, from suspected concussion-related hemorrhages to diverse
      structural and neurofibrillary changes to geographic tauopathy. Progressive
      neurodegenerative tauopathy is among the prevailing theories for disease
      pathogenesis currently, although this may be overly simplistic. Careful
      examination of historical cases reveals both misdiagnoses and a likelihood that
      dementia pugilistica at that time was caused by cumulative structural brain
      injury. More recent neuropathological studies indicate subclinical and possibly
      static tauopathy in some athletes and non-athletes. Indeed, it is unclear from
      the literature whether retired boxers reach the inflection point that tends
      toward progressive neurodegeneration in the manner of Alzheimer's disease due to
      boxing. Even among historical cases with extreme levels of exposure, progressive
      disease was exceptional.

PMID- 29036832
TI  - Neuropathological Comparison of Adult Onset and Juvenile Huntington's Disease
      with Cerebellar Atrophy: A Report of a Father and Son.
AB  - BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative
      disease caused by a trinucleotide (CAG) repeat expansion in huntingtin (HTT) on
      chromosome 4. Anticipation can cause longer repeat expansions in children of HD
      patients. Juvenile Huntington's disease (JHD), defined as HD arising before age
      20, accounts for 5-10% of HD cases, with cases arising in the first decade
      accounting for approximately 1%. Clinically, JHD differs from the predominately
      choreiform adult onset Huntington's disease (AOHD) with variable presentations,
      including symptoms such as myoclonus, seizures, Parkinsonism, and cognitive
      decline. OBJECTIVE: The neuropathologic changes of AOHD are well characterized,
      but there are fewer reports that describe the neuropathology of JHD. Here we
      report a case of a six-year-old boy with paternally-inherited JHD caused by 169
      CAG trinucleotide repeats who presented at age four with developmental delay,
      dysarthria, and seizures before dying at age 6. The boy's clinical presentation
      and neuropathological findings are directly compared to those of his father, who
      presented with AOHD and 54 repeats. METHODS: A full autopsy was performed for the
      JHD case and a brain-only autopsy was performed for the AOHD case.
      Histochemically- and immunohistochemically-stained slides were prepared from
      formalin-fixed, paraffin-embedded tissue sections. RESULTS: Both cases had
      neuropathology corresponding to Vonsattel grade 3. The boy also had cerebellar
      atrophy with huntingtin-positive inclusions in the cerebellum, findings not
      present in the father. CONCLUSIONS: Autopsies of father and son provide a unique
      opportunity to compare and contrast the neuropathologic findings of juvenile and
      adult onset HD while also providing the first immunohistochemical evidence of
      cerebellar involvement in JHD. Additionally this is the first known report to
      include findings from peripheral tissue in a case of JHD.

PMID- 29036833
TI  - Gsk3beta aggravates the depression symptoms in chronic stress mouse model.
AB  - Depression caused by genetic and environmental factors is acomplicated disease.
      Here, it is demonstrated that glycogen synthase kinase-3beta is highly expressed
      and phosphorylated in the brain of a chronic stress mouse. Inhibition of glycogen
      synthase kinase-3betaleads to decreased depression-like symptoms which manifest
      in open-field test, tail-suspension test, forced swim test, and a novelty
      suppressed feeding test. It was also found that beta-catenin is attenuated, and
      its target genes Cyclin D1 and c-Myc are down-regulated. Glycogen synthase kinase
      3beta was also found to inhibit Erk-Creb-BDNF signaling. These results show that
      glycogen synthase kinase-3beta may promote the progression of depression.
      Therefore, targeting glycogen synthase kinase-3beta may be an effective
      therapeutic strategy.

PMID- 29036834
TI  - Association between SORL1 polymorphisms and the risk of Alzheimer's disease.
AB  - A meta-analysis was performed to identify empirical data assessing the effects of
      a single nucleotide polymorphisms of sortilin related receptor on Alzheimer's
      disease based on 14 studies involving 37941 cases and 49727 control studies.
      Analysis showed, (i) Increased risk between the single nucleotidepolymorphisms
      (rs641120, rs1010159) and Alzheimer's disease susceptibility inAsian populations,
      (ii) Single nucleotide polymorphism rs689021 was associatedwith decreased risk in
      Caucasians, and (iii) Single nucleotide polymorphismrs641120 was detected as a
      decreased risk in both populations. Given thesedata, crucial evidence is provided
      to demonstrate that a significantrelationship exists between SORL1 polymorphisms
      and susceptibility to Alzheimer's disease.

PMID- 29036835
TI  - Therapeutic role of long non-coding RNA TCONS_00019174 in depressive disorders is
      dependent on Wnt/beta-catenin signaling pathway.
AB  - Chronic stress is one of the major causes that lead to major depressive disorder,
      which is a prevalent mood disorder worldwide. Many patients with major depressive
      disorder do not benefit from available medication due to the complex etiology of
      the condition. Recently, long non-coding RNAs, molecular switches of downstream
      genes expression, have been reported to be involved in the pathogenesis of major
      depressive disorder. The long non-coding RNA TCONS_00019174 has been implicated
      in major depressive disorder risk and antidepressant effects, However, the effect
      of long non-coding RNA TCONS_00019174 on antidepressant responses has not been
      investigated. This study is designed to determine whether altered expression of
      long non-coding RNA TCONS_00019174 contributes to depression-like behaviors
      associated with chronic stress. We found that mice exposed to chronic ultra-mild
      stress displayed apparent depression-like behaviors and decreased expression of
      long non-coding RNA TCONS_00019174 in hippocampus. Both changed behaviors and
      long non-coding RNA TCONS_00019174 expression level were rescued by chronic
      treatment with imipramine. Viral-mediated long non-coding RNA TCONS_00019174 over
      expression in hippocampal neurons improved the behaviors of mice exposed to
      chronic ultra-mild stress. Further, it was found long non-coding RNA
      TCONS_00019174 over expression upregulated phosphorylated-GSK3beta (p-GSK3beta)
      protein and beta-catenin in the hippocampus. These findings suggest that long non
      coding RNA TCONS_00019174 exerts antidepressant-like effect in mice by activating
      a Wnt/beta-catenin pathway, and that long non-coding RNA may serve as a potential
      therapeutic target for major depressive disorder in clinical application.

PMID- 29036836
TI  - A Panel of Slow-Channel Syndrome Mice Reveals a Unique Locomotor Behavioral
      Signature.
AB  - Muscle nicotinic acetylcholine receptor (nAChR) mutations can lead to altered
      channel kinetics and neuromuscular junction degeneration, a neurodegenerative
      disorder collectively known as slow-channel syndrome (SCS). A multivariate
      analysis using running wheels was used to generate activity profiles for a
      variety of SCS models, uncovering unique locomotor patterns for the different
      nAChR mutants. Particularly, the alphaL251T and EL269F mutations exhibit
      decreased event distance, duration, and velocity over a period of 24 hours. Our
      approach suggests a robust relationship between the pathophysiology of SCS and
      locomotor activity.

PMID- 29036838
TI  - Neurosexuality: A transdisciplinary approach to sexuality in neurorehabilitation.

PMID- 29036839
TI  - Stroke and sexual functioning: A literature review.
AB  - BACKGROUND: Stroke has multiple impacts on patients' sexual functioning, be it
      directly caused by the neurological lesion (s) or indirectly triggered via other
      psychophysiological processes. Despite a growing number of publications,
      sexuality is still rarely addressed in the stroke literature - yet, patients have
      indicated their need for sexual rehabilitation services. OBJECTIVE: To provide a
      literature review on post-stroke sexual functioning as well as available
      rehabilitation programs targeting patients' sexuality. METHODS: A systematic
      literature review was conducted on PubMed using the following key words and their
      combination: "stroke", "sexuality", "stroke characteristics", "hemisphere",
      "sexual", and "sexual dysfunction". RESULTS: Existing data suggests the existence
      of significant associations between stroke and male and female sexual dysfunction
      (SD) as well as desire/libido and sexual satisfaction. The exact contribution of
      patients' neurological profile (stroke laterality, location, and severity) on
      their SD remains inconclusive with research providing mixed findings.
      Psychological factors are shown to play a significant part in the development of
      patients' SDs. A few intervention programs have been developed to specifically
      guide health professionals when addressing patients' needs regarding their sexual
      recovery. CONCLUSION: Sexual rehabilitation needs to be an integrative part of
      stroke patients' rehabilitation process, preferably at the interdisciplinary
      level.

PMID- 29036840
TI  - Efficacy of memory aids after traumatic brain injury: A single case series.
AB  - BACKGROUND: Individuals living with traumatic brain injury commonly have
      difficulties with prospective memory-the ability to remember a planned action at
      the intended time. Traditionally a memory notebook has been recommended as a
      compensatory memory aid. Electronic devices have the advantage of providing a cue
      at the appropriate time to remind participants to refer to the memory aid and
      complete tasks. Research suggests these have potential benefit in
      neurorehabilitation. OBJECTIVE: This study aimed to investigate the efficacy of a
      memory notebook and specifically a smartphone as a compensatory memory aid.
      METHODS: A single case series design was used to assess seven participants. A no
      intervention baseline was followed by training and intervention with either the
      smartphone alone, or a memory notebook and later the smartphone. Memory was
      assessed with weekly assigned memory tasks. RESULTS: Participants using a
      smartphone showed improvements in their ability to complete assigned memory tasks
      accurately and within the assigned time periods. Use of a smartphone provided
      additional benefits over and above those already seen for those who received a
      memory notebook first. CONCLUSIONS: Smartphones have the potential to be a useful
      and cost effective tool in neurorehabilitation practice.

PMID- 29036841
TI  - Home and family in cognitive rehabilitation after brain injury: Implementation of
      social reserves.
AB  - The focus of the present article is the home and family environment of patients
      suffering acquired brain injury. In order to obtain the optimal outcome of
      posttraumatic cognitive rehabilitation it is important (a) to obtain a sufficient
      intensity of rehabilitative training, (b) to achieve the maximum degree of
      generalization from formalized training to the daily environment of the patient,
      and (c) to obtain the best possible utilization of "cognitive reserves" in the
      form of cognitive abilities and "strategies" acquired pretraumatically.
      Supplementing the institution-based cognitive training with (potentially computer
      based) home-based training these three goals may more easily be met. Home-based
      training supports a higher intensity of training. Training in the home
      environment also allows better utilization of cognitive strategies acquired
      pretraumatically and more direct transfer of training results from formalized
      training to activities of daily living of the patient.

PMID- 29036842
TI  - Investigating the discrepancy between subjective and objective cognitive
      impairment following acquired brain injury: The role of psychological affect.
AB  - BACKGROUND: Previous research examining the use of self-reported cognitive
      impairment as a reliable predictor of actual objective cognitive impairment (OCI)
      has provided mixed results. OBJECTIVE: The current study aimed to examine the
      potential discrepancy between subjective and objective cognitive impairment in a
      sample of individuals with an acquired brain injury (ABI). METHOD: Twenty-four
      participants, recruited from a community brain injury service, completed an
      objective neuropsychological assessment and a series of self-report
      questionnaires assessing psychological affect and perceived cognitive
      difficulties. RESULTS: Correlational analyses revealed no association between
      objective cognitive impairment and self-reported subjective cognitive impairment.
      Conversely, psychological affect, such as anxiety and depression, was found to be
      highly correlated with subjective cognitive impairment. A hierarchical regression
      analysis revealed psychological affect as a significant predictor of subjective
      cognitive impairment. Objectively measured cognitive impairment was found to be
      non-significant. CONCLUSIONS: These findings suggest that an individual's
      subjective experience of their cognitive difficulties following ABI are not
      associated with their actual objective cognitive impairment. Clinicians may
      benefit from considering other possible psychological factors that may play a
      more crucial role in a patient's appraisals of their cognitive impairments.

PMID- 29036844
TI  - Multiple sclerosis and sexual dysfunction: A need for further education and
      interdisciplinary care.
AB  - BACKGROUND: Multiple sclerosis (MS) is an autoimmune condition affecting young
      women and men, resulting in varied disabilities, including sexual dysfunction.
      OBJECTIVE: This narrative review aims to describe the prevalence,
      pathophysiology, and impact of sexual dysfunction in people with MS (PwMS);
      provide a review of current assessment and treatment strategies; and offer
      considerations for future care. METHODS: Literature review was performed to
      identify primary and secondary sources discussing sexual dysfunction in PwMS.
      RESULTS: Sexual dysfunction is common in PwMS and can occur throughout the
      disease course. Sexual dysfunction is associated with depression, reduced quality
      of life, and may have broader implications related to relationships, fertility,
      pregnancy, and parenting. The etiology is often multifactorial and can be
      classified as primary, secondary, or tertiary dysfunction. Sexual dysfunction in
      PwMS is underdiagnosed and undertreated; however, many healthcare providers may
      already have the skills required to care for PwMS with sexual dysfunction.
      CONCLUSIONS: Additional education for providers regarding the approach to
      assessment and management of sexual dysfunction, their potential role in
      treatment, and available specialized resources is needed. The role of
      interdisciplinary care with collaboration among providers should be considered.
      Further research should evaluate the impact of specific assessment tools and
      treatments on sexual dysfunction in PwMS.

PMID- 29036843
TI  - Aberrant peak lactate response in MS.
AB  - BACKGROUND: The peak blood lactate response to an exhaustive exercise test in a
      number of chronic conditions has been shown to differ from that seen in healthy,
      untrained individuals. However, this has not been investigated for patients with
      multiple sclerosis (MS). OBJECTIVE: The main objective was to determine and
      compare the peak blood lactate response to exercise and the maximal workload
      between two groups of MS patients with different illness severity. METHODS:
      Twenty-five patients with a relapsing-remitting disease course (Group RR) and 41
      patients with a secondary- or primary chronic progressive disease course (group
      CP) performed an exhaustive incremental bicycle ergometry. Peak blood lactate,
      maximal workload, peak oxygen consumption and maximal heart rate were measured.
      RESULTS: The peak blood lactate levels and maximal workload differed
      significantly between the groups (group CP < group RR; p < 0.001). Furthermore
      spiroergometric peak performance markers in both groups were significantly lower
      than predicted for healthy age and sex matched untrained groups. CONCLUSION: A
      reduced peak blood lactate response to exercise is a novel finding for MS
      patients. This calls into doubt if the lactate performance tests and lactate
      thresholds used for healthy individuals can be transferred to MS patients.

PMID- 29036837
TI  - Simvastatin as a Potential Disease-Modifying Therapy for Patients with
      Parkinson's Disease: Rationale for Clinical Trial, and Current Progress.
AB  - Many now believe the holy grail for the next stage of therapeutic advance
      surrounds the development of disease-modifying approaches aimed at intercepting
      the year-on-year neurodegenerative decline experienced by most patients with
      Parkinson's disease (PD). Based on recommendations of an international committee
      of experts who are currently bringing multiple, potentially disease-modifying, PD
      therapeutics into long-term neuroprotective PD trials, a clinical trial involving
      198 patients is underway to determine whether Simvastatin provides protection
      against chronic neurodegeneration. Statins are widely used to reduce
      cardiovascular risk, and act as competitive inhibitors of HMG-CoA reductase. It
      is also known that statins serve as ligands for PPARalpha, a known arbiter for
      mitochondrial size and number. Statins possess multiple cholesterol-independent
      biochemical mechanisms of action, many of which offer neuroprotective potential
      (suppression of proinflammatory molecules & microglial activation, stimulation of
      endothelial nitric oxide synthase, inhibition of oxidative stress, attenuation of
      alpha-synuclein aggregation, modulation of adaptive immunity, and increased
      expression of neurotrophic factors). We describe the biochemical, physiological
      and pharmaceutical credentials that continue to underpin the rationale for taking
      Simvastatin into a disease-modifying trial in PD patients. While unrelated to the
      Simvastatin trial (because this conducted in patients who already have PD), we
      discuss conflicting epidemiological studies which variously suggest that statin
      use for cardiovascular prophylaxis may increase or decrease risk of developing
      PD. Finally, since so few disease-modifying PD trials have ever been launched
      (compared to those of symptomatic therapies), we discuss the rationale of the
      trial structure we have adopted, decisions made, and lessons learnt so far.

PMID- 29036845
TI  - Sexual concerns after Spinal Cord Injury: An update on management.
AB  - BACKGROUND: Spinal Cord Injury (SCI) causes neurological impairment with
      resultant neurogenic sexual dysfunction which can compound preexisting
      psychological and medical sexual concerns. Understanding these concerns is
      important in managing the lifelong needs of persons with SCIs. OBJECTIVES: To
      provide an overview of the impact of SCI on sexuality along with a framework for
      treatment of sexual concerns. To briefly review male infertility and its
      treatments and pregnancy in females after SCI. METHODS: Interdisciplinary
      literature review and synthesis of information. RESULTS: The average age at SCI
      is increased, thus persons with SCIs may have preexisting sexual concerns. Sexual
      activity and satisfaction are decreased after SCI. Psychogenic sexual arousal is
      related to remaining sensation in the T11-L2 dermatomes. Orgasm occurs in
      approximately 50% of persons with SCIs with all injuries except subjects with
      complete lower motor neuron (LMN) injuries affecting the lowest sacral segments A
      structured approach to treatment including assessing preinjury function,
      determining the impact of injury, education, assessing and treating iatrogenic
      sexual dysfunction and treatment of concomitant problems is recommended. Basic
      and advanced methods to improve sexual arousal and orgasm are discussed and
      treatment of anejaculation and issues associated with pregnancy and SCI are
      reviewed. CONCLUSIONS: Sexual satisfaction is impaired after SCI; however,
      education and new therapies can improve responsiveness. Future research is
      warranted to improve sexual function and fertility potential in persons with
      SCIs.

PMID- 29036846
TI  - Perceptions of sexuality in individuals with Amyotrophic Lateral Sclerosis (ALS)
      and their treating clinicians.
AB  - INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) may not affect an individual's
      sexual function directly, but it can indirectly impact their sexual activity.
      Sexual partners often become caregivers, diminishing sexuality within a
      relationship. This can result in decline of quality of life. OBJECTIVE: The study
      aimed to explore the perspectives of individuals with ALS and their treating
      clinicians regarding the importance of sexuality in rehabilitation within a
      multidisciplinary ALS center. We hypothesize that individuals with ALS will
      express the need for sexuality-related discussions as a therapy. METHOD:
      Electronic 11-item questionnaires were anonymously completed by individuals with
      ALS (n = 21) and ALS healthcare professionals (n = 81) between August 2014 to
      June 2016. Descriptive statistics were performed in STATA 14. RESULTS: Majority
      (90%, n = 92) of respondents stated that ALS impacts the sexuality of an
      individual with ALS, and agreed that sexuality-related discussion is needed as a
      complementary therapy. Over 75% of clinicians reported they were not familiar
      with any strategies or interventions to help the patients. CONCLUSION: ALS
      indirectly affects sexuality, thus confirming the need for promoting awareness
      regarding sexuality-related topics among individuals with ALS and healthcare
      professionals. ALS multidisciplinary clinics need to improve their delivery of
      care to address sexual rehabilitation as a complementary therapy.

PMID- 29036847
TI  - Trail Making Test: Normative data for the Latin American Spanish-speaking
      pediatric population.
AB  - OBJECTIVE: To generate normative data for the Trail Making Test (TMT) in Spanish
      speaking pediatric populations. METHOD: The sample consisted of 3,337 healthy
      children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala,
      Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant
      was administered the TMT as part of a larger neuropsychological battery. The TMT
      A and TMT-B scores were normed using multiple linear regressions and standard
      deviations of residual values. Age, age2, sex, and mean level of parental
      education (MLPE) were included as predictors in the analyses. RESULTS: The final
      multiple linear regression models showed main effects for age on both scores,
      such that as children needed less time to complete the test while they become
      older. TMT-A scores were affected by age2 for all countries except, Cuba,
      Guatemala, and Puerto. TMT-B scores were affected by age2 for all countries
      except, Guatemala and Puerto Rico. Models indicated that children whose parent(s)
      had a MLPE >12 years of education needed less time to complete the test compared
      to children whose parent(s) had a MLPE <=12 years for Mexico and Paraguay in TMT
      A scores; and Ecuador, Mexico, Paraguay, and Spain for TMT-B scores. Sex affected
      TMT-A scores for Chile, Cuba, Mexico, and Peru, in that boys needed less time to
      complete the test than girls. Sex did not affect TMT-B scores. CONCLUSIONS: This
      is the largest Spanish-speaking pediatric normative study in the world, and it
      will allow neuropsychologists from these countries to have a more accurate
      approach to interpret the TMT in pediatric populations.

PMID- 29036848
TI  - Concentration Endurance Test (d2): Normative data for Spanish-speaking pediatric
      population.
AB  - OBJECTIVE: To generate normative data for the Concentration Endurance Test (d2)
      in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373
      healthy children from nine countries in Latin America (Chile, Cuba, Ecuador,
      Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each
      participant was administered the d2 test as part of a larger neuropsychological
      battery. The Total number of items processed (TN), Total number of correct
      responses (CR), Total performance (TP), and Concentration performance (CP) scores
      were normed using multiple linear regressions and standard deviations of residual
      values. Age, age2, sex, and mean level of parental education (MLPE) were included
      as predictors in the analyses. RESULTS: The final multiple linear regression
      models showed main effects for age on all scores, such that scores increased
      linearly as a function of age. TN scores were affected by age2 for Guatemala and
      Puerto Rico; CR scores were affected by age2 for Mexico; TP scores were affected
      by age2 for Chile, Mexico, Puerto Rico, and Spain; and CP scores for Mexico and
      Spain. Models indicated that children whose parents had a MLPE >12 years obtained
      higher scores compared to children whose parents had a MLPE<=12 years for Mexico
      and Spain in all scores, and Puerto Rico for TN, CR, and TP, and Guatemala and
      Paraguay for CP scores. Sex affect the scores for Ecuador and Honduras (CP
      scores). CONCLUSIONS: This is the largest Spanish-speaking pediatric normative
      study in the world, and it will allow neuropsychologists from these countries to
      have a more accurate approach to interpret the d2 test in pediatric populations.

PMID- 29036849
TI  - Newly developed Learning and Verbal Memory Test (TAMV-I): Normative data for
      Spanish-speaking pediatric population.
AB  - OBJECTIVE: To generate normative data for the Learning and Verbal Memory Test
      (TAMV-I) in Spanish-speaking pediatric populations. METHOD: The sample consisted
      of 4,373 healthy children from nine countries in Latin America (Chile, Cuba,
      Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain.
      Each participant was administered the TAMV-I as part of a larger
      neuropsychological battery. Free recall, memory delay and recognition scores were
      normed using multiple linear regressions and standard deviations of residual
      values. Age, age2, sex, and mean level of parental education (MLPE) were included
      as predictors in the analyses. RESULTS: The final multiple linear regression
      models indicated main effects for age on all scores, such that scores increased
      linearly as a function of age. Age2 had a significant effect in all countries
      except Cuba, and Puerto Rico for free recall score; a significant effect for
      memory delay score in all countries except Cuba and Puerto Rico; and a
      significant effect for recognition score in in all countries except Guatemala,
      Honduras, and Puerto Rico. Models showed an effect for MLPE in Chile (free
      recall), Honduras (free recall), Mexico (free recall), Puerto Rico (free recall,
      memory delay, and recognition), and Spain (free recall and memory delay). Sex
      affected free recall score for Cuba, Ecuador, Guatemala, Mexico, Paraguay, Peru,
      and Spain, memory delay score for all countries except Chile, Paraguay, and
      Puerto Rico, and recognition score for Ecuador, Mexico, Peru, and Spain, with
      girls scoring higher than boys. CONCLUSIONS: This is the largest Spanish-speaking
      pediatric normative study in the world, and it will allow neuropsychologists from
      these countries to have a more accurate way to interpret the TAMV-I with
      pediatric populations.

PMID- 29036850
TI  - Methodology for the development of normative data for Spanish-speaking pediatric
      populations.
AB  - OBJECTIVE: To describe the methodology utilized to calculate reliability and the
      generation of norms for 10 neuropsychological tests for children in Spanish
      speaking countries. METHOD: The study sample consisted of over 4,373 healthy
      children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala,
      Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Inclusion criteria
      for all countries were to have between 6 to 17 years of age, an Intelligence
      Quotient of>=80 on the Test of Non-Verbal Intelligence (TONI-2), and score of <19
      on the Children's Depression Inventory. Participants completed 10
      neuropsychological tests. Reliability and norms were calculated for all tests.
      RESULTS: Test-retest analysis showed excellent or good- reliability on all tests
      (r's>0.55; p's<0.001) except M-WCST perseverative errors whose coefficient
      magnitude was fair. All scores were normed using multiple linear regressions and
      standard deviations of residual values. Age, age2, sex, and mean level of
      parental education (MLPE) were included as predictors in the models by country.
      The non-significant variables (p > 0.05) were removed and the analysis were run
      again. CONCLUSIONS: This is the largest Spanish-speaking children and adolescents
      normative study in the world. For the generation of normative data, the method
      based on linear regression models and the standard deviation of residual values
      was used. This method allows determination of the specific variables that predict
      test scores, helps identify and control for collinearity of predictive variables,
      and generates continuous and more reliable norms than those of traditional
      methods.

PMID- 29036851
TI  - A novel low-cost approach for navigated transcranial magnetic stimulation.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) is commonly used for
      assessing or modulating brain excitability. However, the credibility of TMS
      outcomes depends on accurate and reliable coil placement during stimulation.
      Navigated TMS systems can address this issue, but these systems are expensive for
      routine use in clinical and research environments. OBJECTIVE: The purpose of this
      study was to provide a high-quality open source framework for navigated TMS and
      test its reliability and accuracy using standard TMS procedures. METHODS: A
      navigated TMS system was created using a low-cost 3D camera system (OptiTrack
      Trio), which communicates with our free and open source software environment
      programmed using the Unity 3D gaming engine. The environment is user friendly and
      has functions to allow for a variety of stimulation procedures (e.g., head and
      coil co-registration, multiple hotspot/grid tracking, intuitive matching, and
      data logging). The system was then validated using a static mockup of a TMS
      session. The clinical utility was also evaluated by assessing the repeatability
      and operator accuracy when collecting motor evoked potential (MEP) data from
      human subjects. RESULTS: The system was highly reliable and improved coil
      placement accuracy (position error = 1.2 mm and orientation error = 0.3 degrees )
      as well as the quality and consistency (ICC >0.95) of MEPs recorded during TMS.
      CONCLUSION: These results indicate that the proposed system is a viable tool for
      reliable coil placement during TMS procedures, and can improve accuracy in
      locating the coil over a desired hotspot both within and between sessions.

PMID- 29036852
TI  - Rehabilitation modality and onset differentially influence whisker sensory
      hypersensitivity after diffuse traumatic brain injury in the rat.
AB  - BACKGROUND: As rehabilitation strategies advance as therapeutic interventions,
      the modality and onset of rehabilitation after traumatic brain injury (TBI) are
      critical to optimize treatment. Our laboratory has detected and characterized a
      late-onset, long-lasting sensory hypersensitivity to whisker stimulation in
      diffuse brain-injured rats; a deficit that is comparable to visual or auditory
      sensory hypersensitivity in humans with an acquired brain injury. OBJECTIVE: We
      hypothesize that the modality and onset of rehabilitation therapies will
      differentially influence sensory hypersensitivity in response to the Whisker
      Nuisance Task (WNT) as well as WNT-induced corticosterone (CORT) stress response
      in diffuse brain-injured rats and shams. METHODS: After midline fluid percussion
      brain injury (FPI) or sham surgery, rats were assigned to one of four
      rehabilitative interventions: (1) whisker sensory deprivation during week one or
      (2) week two or (3) whisker stimulation during week one or (4) week two. At 28
      days following FPI and sham procedures, sensory hypersensitivity was assessed
      using the WNT. Plasma CORT was evaluated immediately following the WNT
      (aggravated levels) and prior to the pre-determined endpoint 24 hours later (non
      aggravated levels). RESULTS: Deprivation therapy during week two elicited
      significantly greater sensory hypersensitivity to the WNT compared to week one (p
      < 0.05), and aggravated CORT levels in FPI rats were significantly lower than
      sham levels. Stimulation therapy during week one resulted in low levels of
      sensory hypersensitivity to the WNT, similar to deprivation therapy and naive
      controls, however, non-aggravated CORT levels in FPI rats were significantly
      higher than sham. CONCLUSION: These data indicate that modality and onset of
      sensory rehabilitation can differentially influence FPI and sham rats, having a
      lasting impact on behavioral and stress responses to the WNT, emphasizing the
      necessity for continued evaluation of modality and onset of rehabilitation after
      TBI.

PMID- 29036853
TI  - Smooth leader or sharp follower? Playing the mirror game with a robot.
AB  - BACKGROUND: The increasing number of opportunities for human-robot interactions
      in various settings, from industry through home use to rehabilitation, creates a
      need to understand how to best personalize human-robot interactions to fit both
      the user and the task at hand. In the current experiment, we explored a human
      robot collaborative task of joint movement, in the context of an interactive
      game. OBJECTIVE: We set out to test people's preferences when interacting with a
      robotic arm, playing a leader-follower imitation game (the mirror game). METHODS:
      Twenty two young participants played the mirror game with the robotic arm, where
      one player (person or robot) followed the movements of the other. Each partner
      (person and robot) was leading part of the time, and following part of the time.
      When the robotic arm was leading the joint movement, it performed movements that
      were either sharp or smooth, which participants were later asked to rate.
      RESULTS: The greatest preference was given to smooth movements. Half of the
      participants preferred to lead, and half preferred to follow. Importantly, we
      found that the movements of the robotic arm primed the subsequent movements
      performed by the participants. CONCLUSION: The priming effect by the robot on the
      movements of the human should be considered when designing interactions with
      robots. Our results demonstrate individual differences in preferences regarding
      the role of the human and the joint motion path of the robot and the human when
      performing the mirror game collaborative task, and highlight the importance of
      personalized human-robot interactions.

PMID- 29036854
TI  - Functional repertoire of interleukin-6 in the central nervous system - a review.
AB  - In an aging society with dementia imposing an increasing threat to higher brain
      cognitive functions, understanding the molecular and cellular events of adult
      neurogenesis is imperative. Interleukin-6 (IL-6), along with its agonistic acting
      soluble receptor sIL-6R (the combined proteins are also known as Hyper-IL-6), is
      a promising cytokine that can support neurogenesis under conditions of
      neurodegeneration when neuron replacement is needed. In contrast to the
      previously reported gliogenic effects of activation of the IL-6-signal transducer
      and activator of transcription 3 (STAT3) axis, this review summarizes recent
      studies showing that IL-6 activation can be neurogenic and has potential
      therapeutic applications for the treatment of neurodegenerative diseases such as
      Parkinson's disease.

PMID- 29036855
TI  - Diagnostic criteria for persistent postural-perceptual dizziness (PPPD):
      Consensus document of the committee for the Classification of Vestibular
      Disorders of the Barany Society.
AB  - This paper presents diagnostic criteria for persistent postural-perceptual
      dizziness (PPPD) to be included in the International Classification of Vestibular
      Disorders (ICVD). The term PPPD is new, but the disorder is not. Its diagnostic
      criteria were derived by expert consensus from an exhaustive review of 30 years
      of research on phobic postural vertigo, space-motion discomfort, visual vertigo,
      and chronic subjective dizziness. PPPD manifests with one or more symptoms of
      dizziness, unsteadiness, or non-spinning vertigo that are present on most days
      for three months or more and are exacerbated by upright posture, active or
      passive movement, and exposure to moving or complex visual stimuli. PPPD may be
      precipitated by conditions that disrupt balance or cause vertigo, unsteadiness,
      or dizziness, including peripheral or central vestibular disorders, other medical
      illnesses, or psychological distress. PPPD may be present alone or co-exist with
      other conditions. Possible subtypes await future identification and validation.
      The pathophysiologic processes underlying PPPD are not fully known. Emerging
      research suggests that it may arise from functional changes in postural control
      mechanisms, multi-sensory information processing, or cortical integration of
      spatial orientation and threat assessment. Thus, PPPD is classified as a chronic
      functional vestibular disorder. It is not a structural or psychiatric condition.

PMID- 29036856
TI  - Informal care, employment and quality of life: Barriers and facilitators to
      combining informal care and work participation for healthcare professionals.
AB  - BACKGROUND: In The Netherlands, one out of six Dutch employees has informal care
      tasks; in the hospital and healthcare sector, this ratio is one out of four
      workers. Informal carers experience problems with the combination of work and
      informal care. In particular, they have problems with the burden of
      responsibility, a lack of independence and their health. These problems can
      reveal themselves in a variety of mental and physical symptoms that can result in
      absenteeism, reduction or loss of (work) participation, reduction of income, and
      even social isolation. OBJECTIVE: The aim of the study was to describe the
      factors that informal carers who are employed in healthcare organizations
      identify as affecting their quality of life, labour participation and health.
      METHODS: We conducted an exploratory study in 2013-2014 that included desk
      research and a qualitative study. Sixteen semi-structured interviews were
      conducted with healthcare employees who combine work and informal care. Data were
      analyzed with Atlas-TI. RESULTS: We identified five themes: 1. Fear and
      responsibility; 2. Sense that one's own needs are not being met; 3. Work as an
      escape from home; 4. Health: a lack of balance; and 5. The role of colleagues and
      managers: giving support and understanding. CONCLUSIONS: Respondents combine work
      and informal care because they have no other solution. The top three reasons for
      working are: income, escape from home and satisfaction. The biggest problems
      informal carers experience are a lack of time and energy. They are all tired and
      are often or always exhausted at the end of the day. They give up activities for
      themselves, their social networks become smaller and they have less interest in
      social activities. Their managers are usually aware of the situation, but
      informal care is not a topic of informal conversation or in performance
      appraisals. Respondents solve their problems with colleagues and expect little
      from the organization.

PMID- 29036857
TI  - Outcomes of safe patient handling and mobilization programs: A meta-analysis.
AB  - BACKGROUND: Variability in patient care settings and the range of patient
      handling tasks present challenges in developing and evaluating safe patient
      handling and mobilization (SPHM) programs. OBJECTIVE: We performed a systematic
      meta-analysis of SPHM program evaluations. METHODS: Systematic literature review
      identified published SPHM program evaluations. Injury Rate Ratios (IRR), pre- to
      post-intervention, were used to estimate intervention effects and to examine the
      influence of patient care level, program components, and follow-up time using
      meta-regression. RESULTS: 27 articles reported evaluations from 44 sites.
      Combined effect estimate for all SPHM programs was 0.44 (95% CI 0.36, 0.54),
      reflecting substantial injury reductions after program implementation. While
      specific program components were not associated with greater effectiveness,
      longer follow-up duration was associated with greater injury rate reduction (p =
      0.01) and intervention effects varied by level of care (p = 0.01), with the
      greatest effect in intensive care unit interventions (IRR 0.14; 95% CI 0.07,
      0.30). CONCLUSIONS: SPHM programs appear to be highly effective in reducing
      injuries. More research is needed to identify the most effective interventions
      for different patient care levels.

PMID- 29036859
TI  - From awareness to action: Sudbury, mining and occupational disease in a time of
      change.
AB  - BACKGROUND: Miners work in highly hazardous environments, but surprisingly, there
      are more fatalities from occupational diseases, including cancers, than from
      fatalities from injuries. Over the last few decades, the mining environment has
      become safer with fewer injuries and less exposure to the toxins that lead to
      occupational disease. There have been improvements in working conditions, and a
      reduction in the number of workers exposed, together with an overall improvement
      in the health of miners. OBJECTIVES: This study attempted to gain a deeper
      understanding of the impetus for change to reduce occupational exposures or
      toxins at the industry level. It focuses on one mining community in Sudbury,
      Ontario, with a high cancer rate, and its reduction in occupational exposures. It
      explored the level of awareness of occupational exposures from the perspective of
      industry and worker representatives in some of the deepest mines in the world.
      Although awareness may be necessary, it is often not a sufficient impetus for
      change, and it is this gap between awareness and change that this study explored.
      It examined the awareness of occupational disease as an impetus to reducing toxic
      exposures in the mining sector, and explores other forces of change at the
      industrial and global levels that have led to an impact on occupational exposures
      in mining. METHODS: From 2014 and 2016, 60 interviews were conducted with
      individuals who were part of, or witness to the changes in mining in Sudbury.
      From these, 12 labour and 10 industry interviews and four focus groups were
      chosen for further analysis to gain a deeper understanding of industry and
      labour's views on the changes in mining and the impact on miners' health from
      occupational exposures. The results from this subsection of the data is the focus
      for this paper. RESULTS: The themes that emerged told a story about Sudbury.
      There is awareness of occupational exposures, but this awareness is dwarfed in
      comparison to the attention that is given to the tragic fatal injuries from
      injuries and accidents. The mines are now owned by foreign multinationals with a
      change from an engaged, albeit paternalistic sense of responsibility for the
      health of the miners, to a less responsive or sympathetic workplace culture.
      Modernization has led to the elimination, substitution, or reduction of some of
      the worst toxins, and hence present-day miners are less exposed to hazards that
      lead to occupational disease than they were in the past. However, modernization
      and the drop in the price of nickel has also led to a precipitous reduction in
      the number of unionized miners, a decline in union power, a decline in the
      monitoring of present-day exposures, and an increase in non-unionized contract
      workers. The impact has been that miners have lost their solidarity and power to
      investigate, monitor or object to present-day exposures. CONCLUSIONS: Although an
      increase in the awareness of occupational hazards has made a contribution to the
      reduction in occupational exposures, the improvement in health of miners may be
      considered more as a "collateral benefit" of the changes in the mining sector.
      Multiple forces at the industrial and global level have differentially led to an
      improvement in the working and living environment. However, with the loss of
      union power, the miners have lost their major advocate for miner health.

PMID- 29036860
TI  - Prevalence of work-related musculoskeletal injuries among South Indian hand
      screen-printing workers.
AB  - BACKGROUND: Hand screen-printing (HSP) plays a predominant role in textile
      industries in developing countries. Workers from HSP industry were mostly
      affected by musculoskeletal injury due to monotonous, and prolonged work nature
      and poor workplace environment. OBJECTIVE: The present study aims to investigate
      the prevalence of work-related musculoskeletal disorder (MSD) symptoms and risk
      factors associated among the HSP industry workers. METHODS: Cochran's sample size
      for categorical data was used to select 385 HSP workers of 1000 samples from
      various provinces of Tamil Nadu, INDIA. Modified Nordic based questionnaire was
      used to assess the musculoskeletal injuries and risk factors among HSP workers.
      RESULTS: The statistical analysis revealed that 62.5% workers are prone to MSD
      symptoms with lower back (75.1%), shoulder (66.2%), knees (58.7%), and ankle/feet
      (55.6%). Age, experience, marital status, stress in the job were the risk factors
      which significantly (p < 0.05) associated with the reported MSDs. Further, this
      study result infers that the subjects with higher age and experience are exposed
      higher levels of MSD prevalence of 85.5% and 92.0% respectively in past 12 months
      than other groups. Among the different work categories in HSP task, the workers
      reported with the maximum discomfort during printing work (63.1%) with Odds ratio
      as 10.38 and 95% CI is 6.18-17.4. than the material handling and drying task.
      CONCLUSIONS: Study results infer that HSP workers are prone to lower back and
      shoulder pain followed by knees and ankle feet regions. Socio-demographic
      factors, awkward posture and repetitive movements contribute to cause MSD among
      hand screen-printing workers.

PMID- 29036858
TI  - Musculoskeletal signs in female homecare personnel: A longitudinal
      epidemiological study.
AB  - BACKGROUND: In Sweden, homecare services take care of elderly and disabled
      people, work that often requires heavy lifting and forward bending, resulting in
      high prevalences of pain and work accidents. OBJECTIVE: Using an eight-year
      follow-up, this study determines the prognostic importance of certain
      musculoskeletal signs reported in earlier studies [1, 2] with respect to aspects
      of pain and perceived disability. METHODS: Baseline data has been reported in
      earlier studies of 607 women [1-3]. This study uses a postal questionnaire survey
      and reports the results of eight years post initial study. RESULTS: Segmental
      pain at L4-L5 and/or L5-S1 levels was associated with higher low back pain
      intensity and disability at the eight-year follow-up. A decrease in low back pain
      intensity over eight years was larger for those with segmental pain. The
      important signs in the longitudinal analyses of pain aspects and disability were
      lumbar spinal mobility and segmental pain at L4-L5 and L5-S1 levels, but the
      explained variations were low. CONCLUSION: Evaluation of low lumbar segmental
      pain provocation and mobility should be considered in routine clinical
      assessments, as this type of evaluation provides prognostic pain and disability
      information over time.

PMID- 29036861
TI  - Task intensity influences upper limb and torso kinematics during two common
      overhead Functional Capacity Evaluation tasks.
AB  - BACKGROUND: The Functional Capacity Evaluation (FCE) is a tool used in the return
      to-work process to guide treatment and decision making. Individual abilities and
      maximum capacity can be determined through visual observations of changes in
      mechanics as intensity increases. OBJECTIVE: The purpose of this study was to
      determine kinematic differences between sexes and intensity levels of two common
      FCE tasks to establish normative behaviours. METHODS: Upper limb and torso
      kinematics were collected from 30 participants as they performed the overhead
      lift and overhead work FCE tasks. Mean, maximum, and minimum values were
      calculated for clinically relevant joint angles. Mean and maximum segment
      velocity was also calculated and each variable was tested with a mixed model
      ANOVA. RESULTS: During the overhead lift task, maximum torso flexion and maximum
      torso extension increased from the lightest to the heaviest load. Humeral flexion
      angle at the beginning of the lift and wrist ulnar deviation also increased with
      load. Torso extension, humeral flexion and axial rotation, and wrist extension
      all increased with time during the overhead work task. CONCLUSIONS: Increasing
      intensity during the overhead tasks influenced kinematic variables. These
      observable changes can be used by evaluators to more reliably determine safe
      maximum capacities for each patient and identify compensatory actions.

PMID- 29036862
TI  - Naval Special Warfare (NSW) crewmen demonstrate diminished cervical strength and
      range of motion compared to NSW students.
AB  - BACKGROUND: Cumulative effects of high-impact vertical forces, like those
      experienced on an open-ocean mission, could be an injury concern for the cervical
      spine. OBJECTIVE: Compare cervical range of motion (ROM) and strength measures
      between students and NSW Crewmen and secondarily to compare these measures
      between students and Crewmen separated into three groups based on years of
      service. METHODS: A volunteer sample of 186 students (age: 22.8+/-3.1 years) and
      167 Operators (age: 26.9+/-5.1 years) completed cervical isometric strength (%
      BW) and ROM ( degrees ) measurements using a handheld dynamometer and CROM-3
      device, respectively. Independent samples t-tests were done to evaluate
      differences between students and Crewmen. Analysis of Variance and appropriate
      post-hoc tests were calculated to compare students to Crewmen separated into
      three groups based on years of service. Data is reported as mean+/-SD and
      (student mean vs. Operator mean). RESULTS: Students demonstrated higher flexion
      strength (21.7+/-4.9 vs. 19.1+/-5.0) and greater ROM: flexion (54.3+/-10.6 vs.
      51.2+/-9.2), and extension (77.0+/-14.4 vs. 71.3+/-11.4) than Crewmen. Students
      demonstrated greater flexion strength than Crewmen with <=2 (19.4+/-5.1), 3-6
      (19.4+/-5.3), and >=7 (18.6+/-4.7) years of service. CONCLUSIONS: Students
      demonstrated greater cervical strength and ROM. A trend of decreasing
      ROM/strength in Crewmen with greater years of service was also observed.

PMID- 29036863
TI  - When helpers need help: A case study on the 2012 earthquakes in Italy.
AB  - BACKGROUND: After two strong earthquakes in the Emilia region in Italy, many HCWs
      had to deal with the psychological consequences of the aftershocks. OBJECTIVE:
      The aims of this case study were a) to describe the psychosocial condition of the
      HCWs affected by the earthquake; b) to present an intervention immediately after
      the earthquake on HCWs in a post-disaster situation using a mixed-method
      approach. METHODS: A mixed-method study was conducted collecting qualitative data
      (during Group Counselling sessions) and quantitative data (through
      questionnaires). RESULTS: The results suggested that the impact of the earthquake
      was very strong, as more than 80% perceived at least a severe impact event
      capable of altering their ability to function; most of the thoughts and feelings
      were related to death and fear. CONCLUSIONS: This study adds knowledge about how
      to plan interventions aiming to help those workers at both individual and
      organisational level.

PMID- 29036864
TI  - Employment pathways of individuals with spinal cord injury living in Switzerland:
      A qualitative study.
AB  - BACKGROUND: Labour market participation (LMP) represents a key goal of
      rehabilitation for individuals with spinal cord injury (SCI). To achieve this
      goal, Swiss SCI rehabilitation centres seek, together with their clients, viable
      follow-up solutions for returning to work after initial rehabilitation. However,
      the long-term outcomes of such vocational follow-up solutions have not been
      investigated so far, and there is a paucity of knowledge regarding the various
      types of employment pathways that persons with SCI living in Switzerland may
      experience. OBJECTIVE: To examine long-term employment pathways as experienced by
      individuals with SCI living in Switzerland. METHODS: A qualitative descriptive
      study design involving narrative interviews with individuals who completed
      vocational rehabilitation (VR) during their initial rehabilitation. Interviews
      were transcribed verbatim, and data analysed using an inductive thematic analysis
      approach. RESULTS: The analysis of the 15 interviews revealed four employment
      pathways: the pathway of no paid work, the pathway of retraining, the pathway of
      job adaptation and the pathway of continuing work. CONCLUSIONS: Apart from three
      pathways leading towards paid employment, our results revealed one pathway that
      was characterized by permanent unemployment. Individuals facing a pathway of no
      paid work may benefit from more custom-made vocational follow-up solutions and
      prolonged job coaching after initial VR.

PMID- 29036865
TI  - Differences in low back pain occurrence over a 6-month period between four
      recovery-stress groups.
AB  - BACKGROUND: Psychosocial work factors and general recovery experiences are
      hypothesised to influence the risk of low back pain (LBP) occurrence by
      influencing the acute recovery-stress state. So far, however, direct links
      between the acute recovery-stress state and LBP occurrence have not been
      investigated in detail. OBJECTIVE: The aim of this study was to investigate
      differences in low back pain occurrence between four distinct recovery-stress
      groups over a period of 6 month. METHODS: A prospective cohort study with a 3
      month and 6-month follow-up measurement was conducted in a sample of
      administrative employees (N = 271). First, the sample was divided into four
      distinct recovery-stress groups by cluster analysis. Subsequently, differences in
      LBP occurrence between these four groups and the Relative Risk (RR) were
      analysed. RESULTS: Overall, groups with higher stress than recovery scores showed
      a higher risk of LBP occurrence compared to those groups with lower stress than
      recovery scores. Furthermore, the group with the highest stress and lowest
      recovery scores showed a significant higher proportion of LBP occurrence after
      six months than the group with the lowest stress and highest recovery scores (RR
      = 7.29). CONCLUSION: The results indicate the relevance of the acute recovery
      stress state for LBP occurrence.

PMID- 29036866
TI  - The prevalence of occupational musculoskeletal disorders in Iran: A meta-analysis
      study.
AB  - BACKGROUND: Prevention of Work-Related Musculoskeletal Disorders (WRMSDs) is
      crucial as they jeopardize the well-being of the workforce in workplaces and are
      prevalent in developed and developing countries. OBJECTIVE: This study aimed to
      determine the prevalence of WRMSDs among Iranian workers. METHODS: A systematic
      review and meta-analysis of WRMSDs in Iran was performed by searching relevant
      keywords in authentic databases and search engines such as SID, Google Scholar,
      Medlib and PubMed. Twenty-seven published articles in the field of WRMSDs from
      2001 to 2010 were searched. Meta-analysis and random effects approach were used
      to analyze data. Heterogeneity investigation of articles was done using I2 index.
      RESULTS: The total sample size was 6,090 workers with a mean of 225 samples per
      study. The upper and lower back had the highest prevalence rate of self-reported
      WRMSDs with 38.1% (95% CI: 29.9-46.4), and 50% (95% CI: 42.5-57.5), respectively.
      Also, knee had the highest prevalence among lower extremity disorders with 42.1%
      prevalence rate (95% CI:35.1-49.1). CONCLUSIONS: A high prevalence of WRMSDs in
      upper and lower limbs was reported in Iran. Trainings with regard to occupational
      ergonomics and industrial hygiene programs were recommended for minimizing the
      work-related risks of musculoskeletal disorders.

PMID- 29036868
TI  - A modified Job Demand, Control, Support model for active duty police.
AB  - BACKGROUND: The Job Demand Control Support model (JDCS) is one of the most widely
      used theoretical models relating job characteristics to health and wellbeing.
      OBJECTIVE: This study aimed to assess the predictive power of the JDCS model for
      determining job satisfaction and fatigue in uniformed Swedish police. An
      additional aim was to determine if predictive power of the model would be
      improved with the addition of two occupation specific items. METHODS:
      Questionnaire data, based upon the Swedish Work Environment Survey were collected
      from Swedish police (n = 4244). A hierarchical multiple regression analysis was
      run to explore the predictive value of the model and to determine if the
      additional variables improved predictive power with respect to job satisfaction
      and fatigue. RESULTS: Regression analysis demonstrated that the JDSC model had
      high predictive power in relation to job satisfaction and fatigue. Job demands
      was the strongest predictor of fatigue (14%), while support was the strongest
      predictor of job satisfaction (12%). The addition of exposure to threats
      significantly improved predictive power for both job satisfaction and fatigue,
      while addition of shift work did not significantly affect predictive power of the
      model. CONCLUSIONS: Workplace interventions to address issues related to job
      satisfaction and fatigue in police should focus on maintaining a bearable level
      of job demands and provision of adequate support.

PMID- 29036869
TI  - The relationship between trait self-control, consideration for future consequence
      and organizational citizenship behavior among Chinese employees.
AB  - BACKGROUND: Organizational citizenship behavior (OCB) is important to the
      development of an organization. Research into factors that foster OCB and the
      underlying processes are therefore substantially crucial. OBJECTIVE: The current
      study aimed to test the association between trait self-control and OCB and the
      mediating role of consideration for future consequence. METHOD: Four hundred and
      ninety-four Chinese employees (275 men, 219 women) took part in the study.
      Participants completed a battery of self-report measures online that assessed
      trait self-control, tendencies of consideration of future consequence, and
      organizational citizenship behavior. Path analysis was conducted and
      bootstrapping technique (N = 5000), a resampling method that is asymptotically
      more accurate than the standard intervals using sample variance and assumptions
      of normality, was used to judge the significance of the mediation. RESULTS:
      Results of path analysis showed that trait self-control was positively related to
      OCB. More importantly, the "trait self-control-OCB" link was mediated by
      consideration of future consequence-future, but not by consideration of future
      consequence-immediate. CONCLUSIONS: Employees with high trait self-control engage
      in more organizational citizenship behavior and this link can be partly explained
      by consideration of future consequence-future.

PMID- 29036870
TI  - Development and validation of a new safety climate scale for petrochemical
      industries.
AB  - BACKGROUND: While a considerable body of research has studied safety climate and
      its role as a leading indicator of organizational safety, much of this work has
      been conducted with Western manufacturing samples. OBJECTIVE: The current study
      puts emphasis on the cross-validation of a safety climate model in the non
      Western industrial context of Iranian petrochemical industries. METHODS: The
      current study was performed in one petrochemical company in Iran. The scale was
      developed through conducting a literature review followed by a qualitative study
      with expert participation. After performing a screening process, the initial
      number of items on the scale was reduced to 68. RESULTS: Ten dimensions
      (including management commitment, workers' empowerment, communication, blame
      culture, safety training, job satisfaction, interpersonal relationship,
      supervision, continuous improvement, and reward system) together with 37 items
      were extracted from the exploratory factor analysis (EFA) to measure safety
      climate. Acceptable ranges of internal consistency statistics for the sub-scales
      were observed. Confirmatory factor analysis (CFA) confirmed the construct
      validity of the developed safety climate scale for the petrochemical industry
      workers. The results of reliability showed that the Cronbach's alpha coefficient
      for the designed scale was 0.94. The ICC was obtained 0.92. CONCLUSION: This
      study created a valid and reliable scale for measuring safety climate in
      petrochemical industries.

PMID- 29036871
TI  - Monitoring of need for recovery and prolonged fatigue within the working
      population: Evaluation of reliability and agreement over time.
AB  - BACKGROUND: Need for recovery (NFR) and prolonged fatigue are two important
      concepts for monitoring short- and long-term outcomes of psychological job
      demands within employees. For effective monitoring it is, however, important to
      gain insight in the reproducibility of the instruments that are used. OBJECTIVE:
      The objective was to assess reproducibility of the NFR scale and Checklist
      Individual Strength (CIS), measuring NFR and prolonged fatigue respectively, in
      the working population. METHODS: Longitudinal data from the Maastricht Cohort
      Study (MCS) study was used, capturing 12,140 employees from 45 different
      companies at baseline. A 'working' and 'returning to work' sample was conceived
      for different intervals; 4-month, 1-year, and 2-year. RESULTS: Reliability,
      assessed with the interclass correlation, was high within employees with a stable
      work environment for the NFR scale (0.78) and CIS (0.75). The smallest detectable
      change, assessing the agreement, was 41.20 for the NFR scale and 31.10 for the
      CIS. CONCLUSIONS: Reliability was satisfactory for both the NFR scale and CIS.
      The agreement of both scales to detect a changes within employees was, however,
      less optimal. It is, therefore, suggested that, ideally, both instruments are
      placed within a broader range of instruments to effectively monitor the outcomes
      of psychological job demands.

PMID- 29036872
TI  - Factors influencing the occupational injuries of physical therapists in Taiwan: A
      hierarchical linear model approach.
AB  - BACKGROUND: The evidence literature suggests that physical therapy practitioners
      are subjected to a high probability of acquiring work-related injuries, but only
      a few studies have specifically investigated Taiwanese physical therapy
      practitioners. OBJECTIVE: This study was conducted to determine the relationships
      among individual and group hospital-level factors that contribute to the medical
      expenses for the occupational injuries of physical therapy practitioners in
      Taiwan. PARTICIPANTS: Physical therapy practitioners in Taiwan with occupational
      injuries were selected from the 2013 National Health Insurance Research Databases
      (NHIRD). METHODS: The age, gender, job title, hospitals attributes, and
      outpatient data of physical therapy practitioners who sustained an occupational
      injury in 2013 were obtained with SAS 9.3. SPSS 20.0 and HLM 7.01 were used to
      conduct descriptive and hierarchical linear model analyses, respectively.
      RESULTS: The job title of physical therapy practitioners at the individual level
      and the hospital type at the group level exert positive effects on per person
      medical expenses. Hospital hierarchy moderates the individual-level relationships
      of age and job title with the per person medical expenses. CONCLUSION:
      Considering that age, job title, and hospital hierarchy affect medical expenses
      for the occupational injuries of physical therapy practitioners, we suggest
      strengthening related safety education and training and elevating the self
      awareness of the risk of occupational injuries of physical therapy practitioners
      to reduce and prevent the occurrence of such injuries.

PMID- 29036873
TI  - Fighting against a shortage of truck drivers in logistics: Measures that
      employers can take to promote drivers' work ability and health.
AB  - BACKGROUND: For several years, the transportation industry has been concerned
      about a severe shortage of professional truck drivers. Studies investigating the
      reasons found that poor working conditions and stresses and strains resulting
      from physiological and psychological job demands have had a negative impact on
      drivers' health and ability to work. Nevertheless, until now, most employers have
      refrained from offering measures to support the work ability and well-being of
      drivers, mainly due to financial pressures in the industry. OBJECTIVE: The
      present study was aimed at designing adequate and affordable measures to support
      drivers' health. METHOD: With reference to the Work Ability Index and the house
      of work ability (Ilmarinen & Tuomi, 2004), 56 truck drivers participated in
      guided interviews about their working conditions and health-related problems as
      well as their attitudes, experiences, and desires with respect to being offered
      supportive measures by their employers. RESULTS: The measures derived are
      specific and realizable and expected to be widely accepted by professional
      drivers. They are designed to elicit a positive attitude in the drivers toward
      exercising and to help them overcome related psychological barriers. CONCLUSION:
      The implementation of the recommended measures can be expected to support
      drivers' work ability and help reduce the frictional costs of their employers.

PMID- 29036875
TI  - Three novel accurate pixel-driven projection methods for 2D CT and 3D EPR
      imaging.
AB  - OBJECTIVES: This work aims to explore more accurate pixel-driven projection
      methods for iterative image reconstructions in order to reduce high-frequency
      artifacts in the generated projection image. METHODS: Three new pixel-driven
      projection methods namely, small-pixel-large-detector (SPLD), linear
      interpolation based (LIB) and distance anterpolation based (DAB), were proposed
      and applied to reconstruct images. The performance of these methods was evaluated
      in both two-dimensional (2D) computed tomography (CT) images via the modified
      FORBILD phantom and three-dimensional (3D) electron paramagnetic resonance (EPR)
      images via the 6-spheres phantom. Specifically, two evaluations based on
      projection generation and image reconstruction were performed. For projection
      generation, evaluation was using a 2D disc phantom, the modified FORBILD phantom
      and the 6-spheres phantom. For image reconstruction, evaluations were performed
      using the FORBILD and 6-spheres phantom. During evaluation, 2 quantitative
      indices of root-mean-square-error (RMSE) and contrast-to-noise-ratio (CNR) were
      used. RESULTS: Comparing to the use of ordinary pixel-driven projection method,
      RMSE of the SPLD based least-square algorithm was reduced from 0.0701 to 0.0384
      and CNR was increased from 5.6 to 19.47 for 2D FORBILD phantom reconstruction.
      For 3D EPRI, RMSE of SPLD was also reduced from 0.0594 to 0.0498 and CNR was
      increased from 3.88 to 11.58. In addition, visual evaluation showed that images
      reconstructed in both 2D and 3D images suffered from high-frequency line-shape
      artifacts when using the ordinary pixel-driven projection method. However, using
      3 new methods all suppressed the artifacts significantly and yielded more
      accurate reconstructions. CONCLUSIONS: Three proposed pixel-driven projection
      methods achieved more accurate iterative image reconstruction results. These new
      and more accurate methods can also be easily extended to other imaging
      modalities. Among them, SPLD method should be recommended to 3D and four
      dimensional (4D) EPR imaging.

PMID- 29036874
TI  - Development of a device to reduce the risk of injury in handling unstable loads.
AB  - BACKGROUND: Manual material handling (MMH) task is the most common cause of work
      related musculoskeletal disorders (MSDs). Operators carrying unstable loads were
      recently shown to be at greater risk of back injury compared to workers carrying
      stable loads. OBJECTIVE: This study focused on developing a device to minimize
      trunk muscle activity and cardiovascular demand while handling a 19-liter bottle.
      METHOD: After evaluating several designs, one was selected to be developed,
      manufactured and tested through an experimental study. Healthy participants (n =
      42) manually carried a 19-liter bottle. The carrying technique (i.e., carrying a
      lateral load while holding the load using the dominant hand, pulling the load
      using the developed device, carrying the load on the back using the developing
      device) was the independent variable. The muscular activities (e.g., neck
      extensor, upper trapezius, pectoralis major, deltoid medial, rectus abdominis,
      and erector spinae muscles of the dominant side), cardiac costs, plantar
      pressures, walking speeds, and subjective measures were the dependent variables.
      RESULTS: Results show that carrying the developed device like a backpack
      significantly reduced trunk muscle activity, cardiovascular demand, and plantar
      pressure compared to the usual practice. The present results suggest that
      carrying a 19-liter water bottle using the developed device is likely to
      contribute to lower MSDs. CONCLUSION: Implementation of the develop device
      recommended to lessen the risk of injury when handling unstable loads such as
      liquids.

PMID- 29036876
TI  - Image artifacts and noise reduction algorithm for cone-beam computed tomography
      with low-signal projections.
AB  - This study aims to investigate and test a new image reconstruction algorithm
      applying to the low-signal projections to generate high quality images by
      reducing the artifacts and noise in the cone-beam computed tomography (CBCT). For
      the low-signal and noisy projections, a multiple sampling method is first
      utilized in projection domain to suppress environmental noise, which guarantees
      the accuracy of the data for reconstruction, simultaneously. Next, a fuzzy
      entropy based method with block matching 3D (BM3D) filtering algorithm is
      employed to improve the image quality to reduce artifacts and noise in image
      domain. Then, simulation studies on polychromatic spectrum were performed to
      evaluate the performance of the proposed new algorithm. Study results
      demonstrated significant improvement in the signal-to-noise ratios (SNRs) and
      contrast-to-noise ratios (CNRs) of the images reconstructed using the new
      algorithm. SNRs and CNRs of the new images were averagely 40% and 20% higher than
      those of the previous images reconstructed using the traditional algorithms,
      respectively. As a result, since the new image reconstruction algorithm
      effectively reduced the artifacts and noise, and produced images with better
      contour and grayscale distribution, it has the potential to improve image quality
      using the original CBCT data with the low and missing signals.

PMID- 29036877
TI  - A hybrid CNN feature model for pulmonary nodule malignancy risk differentiation.
AB  - The malignancy risk differentiation of pulmonary nodule is one of the most
      challenge tasks of computer-aided diagnosis (CADx). Most recently reported CADx
      methods or schemes based on texture and shape estimation have shown relatively
      satisfactory on differentiating the risk level of malignancy among the nodules
      detected in lung cancer screening. However, the existing CADx schemes tend to
      detect and analyze characteristics of pulmonary nodules from a statistical
      perspective according to local features only. Enlightened by the currently
      prevailing learning ability of convolutional neural network (CNN), which
      simulates human neural network for target recognition and our previously research
      on texture features, we present a hybrid model that takes into consideration of
      both global and local features for pulmonary nodule differentiation using the
      largest public database founded by the Lung Image Database Consortium and Image
      Database Resource Initiative (LIDC-IDRI). By comparing three types of CNN models
      in which two of them were newly proposed by us, we observed that the multi
      channel CNN model yielded the best discrimination in capacity of differentiating
      malignancy risk of the nodules based on the projection of distributions of
      extracted features. Moreover, CADx scheme using the new multi-channel CNN model
      outperformed our previously developed CADx scheme using the 3D texture feature
      analysis method, which increased the computed area under a receiver operating
      characteristic curve (AUC) from 0.9441 to 0.9702.

PMID- 29036878
TI  - Geometric artifacts reduction for cone-beam CT via L0-norm minimization without
      dedicated phantoms.
AB  - For cone-beam computed tomography (CBCT), transversal shifts of the rotation
      center exist inevitably, which will result in geometric artifacts in CT images.
      In this work, we propose a novel geometric calibration method for CBCT, which can
      also be used in micro-CT. The symmetry property of the sinogram is used for the
      first calibration, and then L0-norm of the gradient image from the reconstructed
      image is used as the cost function to be minimized for the second calibration. An
      iterative search method is adopted to pursue the local minimum of the L0-norm
      minimization problem. The transversal shift value is updated with affirmatory
      step size within a search range determined by the first calibration. In addition,
      graphic processing unit (GPU)-based FDK algorithm and acceleration techniques are
      designed to accelerate the calibration process of the presented new method. In
      simulation experiments, the mean absolute difference (MAD) and the standard
      deviation (SD) of the transversal shift value were less than 0.2 pixels between
      the noise-free and noisy projection images, which indicated highly accurate
      calibration applying the new calibration method. In real data experiments, the
      smaller entropies of the corrected images also indicated that higher resolution
      image was acquired using the corrected projection data and the textures were well
      protected. Study results also support the feasibility of applying the proposed
      method to other imaging modalities.

PMID- 29036879
TI  - Enhancement of digital radiography image quality using a convolutional neural
      network.
AB  - Digital radiography system is widely used for noninvasive security check and
      medical imaging examination. However, the system has a limitation of lower image
      quality in spatial resolution and signal to noise ratio. In this study, we
      explored whether the image quality acquired by the digital radiography system can
      be improved with a modified convolutional neural network to generate high
      resolution images with reduced noise from the original low-quality images. The
      experiment evaluated on a test dataset, which contains 5 X-ray images, showed
      that the proposed method outperformed the traditional methods (i.e., bicubic
      interpolation and 3D block-matching approach) as measured by peak signal to noise
      ratio (PSNR) about 1.3 dB while kept highly efficient processing time within one
      second. Experimental results demonstrated that a residual to residual (RTR)
      convolutional neural network remarkably improved the image quality of object
      structural details by increasing the image resolution and reducing image noise.
      Thus, this study indicated that applying this RTR convolutional neural network
      system was useful to improve image quality acquired by the digital radiography
      system.

PMID- 29036880
TI  - Correction: Zhang, G.; Cheng, G.; Jia, P.; Jiao, S.; Feng, C.; Hu, T.; Liu, H.;
      Du, Y. The Positive Correlation of the Enhanced Immune Response to PCV2 Subunit
      Vaccine by Conjugation of Chitosan Oligosaccharide with the Deacetylation Degree.
      Marine Drugs 2017, 15, 236.
AB  - The authors wish to correct Figure 1 in this paper [1] to be as follows:[...].

PMID- 29036881
TI  - Comparison of In Vitro Assays in Selecting Radiotracers for In Vivo P
      Glycoprotein PET Imaging.
AB  - Positron emission tomography (PET) imaging of P-glycoprotein (P-gp) in the blood
      brain barrier can be important in neurological diseases where P-gp is affected,
      such as Alzheimer's disease. Radiotracers used in the imaging studies are present
      at very small, nanomolar, concentration, whereas in vitro assays where these
      tracers are characterized, are usually performed at micromolar concentration,
      causing often discrepant in vivo and in vitro data. We had in vivo rodent PET
      data of [11C]verapamil, (R)-N-[18F]fluoroethylverapamil, (R)-O-[18F]fluoroethyl
      norverapamil, [18F]MC225 and [18F]MC224 and we included also two new molecules
      [18F]MC198 and [18F]KE64 in this study. To improve the predictive value of in
      vitro assays, we labeled all the tracers with tritium and performed bidirectional
      substrate transport assay in MDCKII-MDR1 cells at three different concentrations
      (0.01, 1 and 50 uM) and also inhibition assay with P-gp inhibitors. As a
      comparison, we used non-radioactive molecules in transport assay in Caco-2 cells
      at a concentration of 10 uM and in calcein-AM inhibition assay in MDCKII-MDR1
      cells. All the P-gp substrates were transported dose-dependently. At the highest
      concentration (50 uM), P-gp was saturated in a similar way as after treatment
      with P-gp inhibitors. Best in vivo correlation was obtained with the
      bidirectional transport assay at a concentration of 0.01 uM. One micromolar
      concentration in a transport assay or calcein-AM assay alone is not sufficient
      for correct in vivo prediction of substrate P-gp PET ligands.

PMID- 29036882
TI  - Biomineralization of Fucoidan-Peptide Blends and Their Potential Applications in
      Bone Tissue Regeneration.
AB  - Fucoidan (Fuc), a natural polysaccharide derived from brown seaweed algae, and
      gelatin (Gel) were conjugated to form a template for preparation of biomimetic
      scaffolds for potential applications in bone tissue regeneration. To the Fuc-Gel
      we then incorporated the peptide sequence MTNYDEAAMAIASLN (MTN) derived from the
      E-F hand domain, known for its calcium binding properties. To mimic the
      components of the extracellular matrix of bone tissue, the Fuc-Gel-MTN assemblies
      were incubated in simulated body fluid (SBF) to induce biomineralization,
      resulting in the formation of beta-tricalcium phosphate, and hydroxyapatite
      (HAp). The formed Fuc-Gel-MTN-beta-TCP/HAP scaffolds were found to display an
      average Young's Modulus value of 0.32 GPa (n = 5) with an average surface
      roughness of 91 nm. Rheological studies show that the biomineralized scaffold
      exhibited higher storage and loss modulus compared to the composites formed
      before biomineralization. Thermal phase changes were studied through DSC and TGA
      analysis. XRD and EDS analyses indicated a biphasic mixture of beta-tricalcium
      phosphate and hydroxyapatite and the composition of the scaffold. The scaffold
      promoted cell proliferation, differentiation and displayed actin stress fibers
      indicating the formation of cell-scaffold matrices in the presence of MT3C3-E1
      mouse preosteoblasts. Osteogenesis and mineralization were found to increase with
      Fuc-Gel-MTN-beta-TCP/HAP scaffolds. Thus, we have developed a novel scaffold for
      possible applications in bone tissue engineering.

PMID- 29036883
TI  - MicroRNA-34a: A Versatile Regulator of Myriads of Targets in Different Cancers.
AB  - MicroRNA-34a (miR-34a) is a tumor suppressor that has attracted considerable
      attention in recent years. It modulates cancer cell invasion, metastasis, and
      drug resistance, and has also been evaluated as a diagnostic and/or prognostic
      biomarker. A number of targets of miR-34a have been identified, including some
      other non-coding RNAs, and it is believed that the modulation of these myriads of
      targets underlines the versatile role of miR-34a in cancer progression and
      pathogenesis. Seemingly appealing results from preclinical studies have advocated
      the testing of miR-34a in clinical trials. However, the results obtained are not
      very encouraging and there is a need to re-interpret how miR-34a behaves in a
      context dependent manner in different cancers. In this review, we have attempted
      to summarize the most recent evidence related to the regulation of different
      genes and non-coding RNAs by miR-34a and the advances in the field of
      nanotechnology for the targeted delivery of miR-34a-based therapeutics and
      mimics. With the emergence of data that contradicts miR-34a's tumor suppressive
      function, it is important to understand miR-34a's precise functioning, with the
      aim to establish its role in personalized medicine and to apply this knowledge
      for the identification of individual patients that are likely to benefit from miR
      34a-based therapy.

PMID- 29036886
TI  - Model-Based Real-Time Non-Rigid Tracking.
AB  - This paper presents a sequential non-rigid reconstruction method that recovers
      the 3D shape and the camera pose of a deforming object from a video sequence and
      a previous shape model of the object. We take PTAM (Parallel Mapping and
      Tracking), a state-of-the-art sequential real-time SfM (Structure-from-Motion)
      engine, and we upgrade it to solve non-rigid reconstruction. Our method provides
      a good trade-off between processing time and reconstruction error without the
      need for specific processing hardware, such as GPUs. We improve the original PTAM
      matching by using descriptor-based features, as well as smoothness priors to
      better constrain the 3D error. This paper works with perspective projection and
      deals with outliers and missing data. We evaluate the tracking algorithm
      performance through different tests over several datasets of non-rigid deforming
      objects. Our method achieves state-of-the-art accuracy and can be used as a real
      time method suitable for being embedded in portable devices.

PMID- 29036885
TI  - Fairness and Eligibility to Long-Term Care: An Analysis of the Factors Driving
      Inequality and Inequity in the Use of Home Care for Older Europeans.
AB  - In contrast with the case of health care, distributional fairness of long-term
      care (LTC) services in Europe has received limited attention. Given the increased
      relevance of LTC in the social policy agenda it is timely to evaluate the
      evidence on inequality and horizontal inequity by socio-economic status (SES) in
      the use of LTC and to identify the socio-economic factors that drive them. We
      address both aspects and reflect on the sensitivity of inequity estimates to
      adopting different definitions of legitimate drivers of care need. Using Survey
      of Health, Ageing and Retirement in Europe (SHARE)data collected in 2013, we
      analyse differences in home care utilization between community-dwelling Europeans
      in nine countries. We present concentration indexes and horizontal inequity
      indexes for each country and results from a decomposition analysis across income,
      care needs, household structures, education achievement and regional
      characteristics. We find pro-poor inequality in home care utilization but little
      evidence of inequity when accounting for differential care needs. Household
      characteristics are an important contributor to inequality, while education and
      geographic locations hold less explanatory power. We discuss the findings in
      light of the normative assumptions surrounding different definitions of need in
      LTC and the possible regressive implications of policies that make household
      structures an eligibility criterion to access services.

PMID- 29036884
TI  - Recent Advances in Mycotoxin Determination for Food Monitoring via Microchip.
AB  - Mycotoxins are one of the main factors impacting food safety. Mycotoxin
      contamination has threatened the health of humans and animals. Conventional
      methods for the detection of mycotoxins are gas chromatography (GC) or liquid
      chromatography (LC) coupled with mass spectrometry (MS), or enzyme-linked
      immunosorbent assay (ELISA). However, all these methods are time-consuming,
      require large-scale instruments and skilled technicians, and consume large
      amounts of hazardous regents and solvents. Interestingly, a microchip requires
      less sample consumption and short analysis time, and can realize the integration,
      miniaturization, and high-throughput detection of the samples. Hence, the
      application of a microchip for the detection of mycotoxins can make up for the
      deficiency of the conventional detection methods. This review focuses on the
      application of a microchip to detect mycotoxins in foods. The toxicities of
      mycotoxins and the materials of the microchip are firstly summarized in turn.
      Then the application of a microchip that integrates various kinds of detection
      methods (optical, electrochemical, photo-electrochemical, and label-free
      detection) to detect mycotoxins is reviewed in detail. Finally, challenges and
      future research directions in the development of a microchip to detect mycotoxins
      are previewed.

PMID- 29036887
TI  - Reference Intervals for Non-Fasting CVD Lipids and Inflammation Markers in
      Pregnant Indigenous Australian Women.
AB  - Indigenous Australians experience high rates of cardiovascular disease (CVD). The
      origins of CVD may commence during pregnancy, yet few serum reference values for
      CVD biomarkers exist specific to the pregnancy period. The Gomeroi gaaynggal
      research project is a program that undertakes research and provides some health
      services to pregnant Indigenous women. Three hundred and ninety-nine non-fasting
      samples provided by the study participants (206 pregnancies and 175 women) have
      been used to construct reference intervals for CVD biomarkers during this
      critical time. A pragmatic design was used, in that women were not excluded for
      the presence of chronic or acute health states. Percentile bands for non-linear
      relationships were constructed according to the methods of Wright and Royston
      (2008), using the xriml package in StataIC 13.1. Serum cholesterol,
      triglycerides, cystatin-C and alkaline phosphatase increased as gestational age
      progressed, with little change seen in high-sensitivity C-Reactive Protein and
      gamma glutamyl transferase. Values provided in the reference intervals are
      consistent with findings from other research projects. These reference intervals
      will form a basis with which future CVD biomarkers for pregnant Indigenous
      Australian women can be compared.

PMID- 29036888
TI  - A Novel Vaping Machine Dedicated to Fully Controlling the Generation of E
      Cigarette Emissions.
AB  - The accurate study of aerosol composition and nicotine release by electronic
      cigarettes is a major issue. In order to fully and correctly characterize
      aerosol, emission generation has to be completely mastered. This study describes
      an original vaping machine named Universal System for Analysis of Vaping (U-SAV),
      dedicated to vaping product study, enabling the control and real-time monitoring
      of applied flow rate and power. Repeatability and stability of the machine are
      demonstrated on flow rate, power regulation and e-liquid consumption. The
      emission protocol used to characterize the vaping machine is based on the AFNOR
      XP-D90-300-3 standard (15 W power, 1 Omega atomizer resistance, 100 puffs
      collected per session, 1.1 L/min airflow rate). Each of the parameters has been
      verified with two standardized liquids by studying mass variations, power
      regulation and flow rate stability. U-SAV presents the required and necessary
      stability for the full control of emission generation. The U-SAV is recognised by
      the French association for standardization (AFNOR), European Committee for
      Standardization (CEN) and International Standards Organisation (ISO) as a vaping
      machine. It can be used to highlight the influence of the e-liquid composition,
      user behaviour and nature of the device, on the e-liquid consumption and aerosol
      composition.

PMID- 29036891
TI  - Total Phenolic and Yellow Pigment Contents and Antioxidant Activities of Durum
      Wheat Milling Fractions.
AB  - The aim of this study was to investigate the distribution of total yellow
      pigments, total phenolic compounds, and their antioxidant activities in various
      durum wheat milling fractions. Carotenoid composition of yellow pigment extract
      was also examined using UPLC. The ABTS radical scavenging activity of the milling
      fractions decreased in the order of short bran/bran > feed flour > flour/semolina
      in both total phenolic and total yellow pigment extracts. Yellow pigments
      extracts from bran, short bran, and feed flour exhibited 5.6-15.4% higher
      antioxidant activity than those of total phenolic extracts from the corresponding
      milling fractions. The UPLC results showed a non-carotenoid peak at Rt 0.47 min
      which was present in fractions of the grain outer layers but absent in semolina
      and flour. This peak absorbed in the UV range of 271 to 327 nm. These
      observations suggest that the unknown peak could be composed of phenolic
      compounds co-extracted in their free form with carotenoids in the polar water
      saturated butanol solvent. The compounds in this peak could result in
      overestimation of carotenoid content and antioxidant activity in bran, short bran
      and feed flour as the peak contributed to 18.3-26.0% of total carotenoids if it
      was taken into account.

PMID- 29036889
TI  - Single Administration of Melatonin Modulates the Nitroxidergic System at the
      Peripheral Level and Reduces Thermal Nociceptive Hypersensitivity in Neuropathic
      Rats.
AB  - Neuropathic pain is a severe condition with unsatisfactory treatments. Melatonin,
      an indolamine, seems to be a promising molecule suitable for this purpose due to
      its well-known anti-inflammatory, analgesic, and antioxidant effects, as well as
      its modulation of the nitroxidergic system. Nevertheless, the data on its
      mechanism of action and potentialities are currently insufficient in this
      pathology, especially at the peripheral level. Thus, this work evaluated the
      effect of a single administration of melatonin in an established mononeuropathy
      pain model that monitors the behaviour and the changes in the nitroxidergic
      system in dorsal root ganglia and skin, which are affected by nervous impairment.
      Experiments were carried out on Sprague Dawley rats subdivided into the sham
      operated (control) and the chronic constriction injured animals, a model of
      peripheral neuropathic pain on sciatic nerve. Single administrations of melatonin
      (5-10 mg/kg) or vehicle were injected intraperitoneally on the 14th day after
      surgery, when the mononeuropathy was established. The animals were behaviourally
      tested for thermal hyperalgesia. The dorsal root ganglia and the plantar skin of
      the hind-paws were removed and processed for the immunohistochemical detection of
      neuronal and inducible nitric oxide synthases. The behavioural results showed an
      increase of withdrawal latency during the plantar test as early as 30 min after
      melatonin administration. The immunohistochemical results indicated a modulation
      of the nitroxidergic system both at dorsal root ganglia and skin level,
      permitting speculate on a possible mechanism of action. We showed that melatonin
      may be a possible therapeutic strategy in neuropathic pain.

PMID- 29036892
TI  - Adaptive Enhancement of X-Band Marine Radar Imagery to Detect Oil Spill Segments.
AB  - Oil spills generate a large cost in environmental and economic terms. Their
      identification plays an important role in oil-spill response. We propose an oil
      spill detection method with improved adaptive enhancement on X-band marine radar
      systems. The radar images used in this paper were acquired on 21 July 2010, from
      the teaching-training ship "YUKUN" of the Dalian Maritime University. According
      to the shape characteristic of co-channel interference, two convolutional filters
      are used to detect the location of the interference, followed by a mean filter to
      erase the interference. Small objects, such as bright speckles, are taken as a
      mask in the radar image and improved by the Fields-of-Experts model. The region
      marked by strong reflected signals from the sea's surface is selected to identify
      oil spills. The selected region is subject to improved adaptive enhancement
      designed based on features of radar images. With the proposed adaptive
      enhancement technique, calculated oil spill detection is comparable to visual
      interpretation in accuracy.

PMID- 29036890
TI  - Recent Advances in SELEX Technology and Aptamer Applications in Biomedicine.
AB  - Aptamers are short DNA/RNA oligonucleotides capable of binding to target
      molecules with high affinity and specificity. The process of selecting an aptamer
      is called Systematic Evolution of Ligands by Exponential Enrichment (SELEX).
      Thanks to the inherit merits, aptamers have been used in a wide range of
      applications, including disease diagnosis, targeted delivery agents and
      therapeutic uses. To date, great achievements regarding the selection,
      modifications and application of aptamers have been made. However, few aptamer
      based products have already successfully entered into clinical and industrial
      use. Besides, it is still a challenge to obtain aptamers with high affinity in a
      more efficient way. Thus, it is important to comprehensively review the current
      shortage and achievement of aptamer-related technology. In this review, we first
      present the limitations and notable advances of aptamer selection. Then, we
      compare the different methods used in the kinetic characterization of aptamers.
      We also discuss the impetus and developments of the clinical application of
      aptamers.

PMID- 29036893
TI  - Development and Validation of a Food Frequency Questionnaire to Estimate Intake
      among Children and Adolescents in Urban Peru.
AB  - Tools to assess intake among children in Latin America are limited. We developed
      and assessed the reproducibility and validity of a semi-quantitative food
      frequency questionnaire (FFQ) administered to children, adolescents, and their
      caregivers in Lima, Peru. We conducted 24-h diet recalls (DRs) and focus groups
      to develop a locally-tailored FFQ prototype for children aged 0-14 years. To
      validate the FFQ, we administered two FFQs and three DRs to children and/or their
      caregivers (N = 120) over six months. We examined FFQ reproducibility by quartile
      agreement and Pearson correlation coefficients, and validity by quartile
      agreement and correlation with DRs. For reproducibility, quartile agreement
      ranged from 60-77% with correlations highest for vitamins A and C (0.31). Age
      adjusted correlations for the mean DR and the second-administered FFQ were
      highest in the 0-7 age group, in which the majority of caregivers completed the
      FFQ on behalf of the child (total fat; 0.67) and in the 8-14 age group, in which
      both the child and caregiver completed the FFQ together (calcium, niacin; 0.54);
      correlations were <0.10 for most nutrients in the 8-14 age group in which the
      caregiver completed the FFQ on the child's behalf. The FFQ was reproducible and
      the first developed and validated to assess various nutrients in children and
      adolescents in Peru.

PMID- 29036894
TI  - How Can Data Drive Policy and Practice in Child Welfare? Making the Link in
      Canada.
AB  - Formal university-child welfare partnerships offer a unique opportunity to begin
      to fill the gaps in the child welfare knowledge base and link child welfare
      services to the realities of practice. With resources from a knowledge
      mobilization grant, a formal partnership was developed between the University of
      Toronto, clinicians, policy analysts, and researchers from child welfare agencies
      across Ontario. The key objectives of the grant included: (1) enhancing the
      capacity of service providers to access and analyze child welfare data to inform
      service and policy decisions; (2) integrating clinical expertise in service and
      policy decisions; and (3) developing a joint research agenda addressing high
      priority knowledge gaps. This partnership was an opportunity to advance the
      evidence base with respect to service provision in Ontario and to create a
      culture of knowledge and evidence that would eventually support more complex
      research initiatives. Administrative data was analyzed for this partnership
      through the Ontario Child Abuse and Neglect Data System (OCANDS)-the first child
      welfare data system in Ontario to track child welfare-involved children and their
      families. Child welfare agencies identified recurrence as an important priority
      and agency-driven analyses were subsequently conducted on OCANDS generated
      recurrence Service Performance Indicators (SPI's). Using an urgent versus chronic
      investigative taxonomy for analyses, findings revealed that the majority of cases
      did not recur within 12 months and cases identified as chronic needs are more
      likely to return to the attention of child welfare authorities. One of the key
      outcomes of the partnership - helping agencies to understand their administrative
      data is described, as are considerations for next steps for future partnerships
      and research.

PMID- 29036895
TI  - Low Cost Lab on Chip for the Colorimetric Detection of Nitrate in Mineral Water
      Products.
AB  - The diagnostics of health status and the quality of drinking water are among the
      most important United Nations sustainable development goals. However, in certain
      areas, wars and instability have left millions of people setting in refugee camps
      and dangerous regions where infrastructures are lacking and rapid diagnostics of
      water quality and medical status are critical. In this work, microfluidic testing
      chips and photometric setups are developed in cheap and portable way to detect
      nitrate concentrations in water. The performed test is designed to work according
      to the Griess procedure. Moreover, to make it simple and usable in areas of low
      resource settings, commercially available Arduino mega and liquid crystal display
      (LCD) shield are utilized to process and display results, respectively. For
      evaluation purposes, different local products of tap water, bottled drinking
      water, and home-filter treated water samples were tested using the developed
      setup. A calibration curve with coefficient of determination (R2) of 0.98 was
      obtained when absorbance of the prepared standard solutions was measured as a
      function of the concentrations. In conclusion, this is the first step towards a
      compact, portable, and reliable system for nitrate detection in water for point
      of-care applications.

PMID- 29036896
TI  - Remote Sensing-Based Quantification of the Impact of Flash Flooding on the Rice
      Production: A Case Study over Northeastern Bangladesh.
AB  - The northeastern region of Bangladesh often experiences flash flooding during the
      pre-harvesting period of the boro rice crop, which is the major cereal crop in
      the country. In this study, our objective was to delineate the impact of the 2017
      flash flood (that initiated on 27 March 2017) on boro rice using multi-temporal
      Landsat-8 OLI and MODIS data. Initially, we opted to use Landsat-8 OLI data for
      mapping the damages; however, during and after the flooding event the acquisition
      of cloud free images were challenging. Thus, we used this data to map the
      cultivated boro rice acreage considering the planting to mature stages of the
      crop. Also, in order to map the extent of the damaged boro area, we utilized
      MODIS data as their 16-day composites provided cloud free information. Our
      results indicated that both the cultivated and damaged boro area estimates based
      on satellite data had strong relationships while compared to the ground-based
      estimates (i.e., r2 values approximately 0.92 for both cases, and RMSE of 18,374
      and 9380 ha for cultivated and damaged areas, respectively). Finally, we believe
      that our study would be critical for planning and ensuring food security for the
      country.

PMID- 29036898
TI  - Highly Sensitive and Selective Hydrogen Gas Sensor Using the Mesoporous SnO2
      Modified Layers.
AB  - It is important to improve the sensitivities and selectivities of metal oxide
      semiconductor (MOS) gas sensors when they are used to monitor the state of
      hydrogen in aerospace industry and electronic field. In this paper, the ordered
      mesoporous SnO2 (m-SnO2) powders were prepared by sol-gel method, and the
      morphology and structure were characterized by X-ray diffraction analysis (XRD),
      transmission electron microscope (TEM) and Brunauer-Emmett-Teller (BET). The gas
      sensors were fabricated using m-SnO2 as the modified layers on the surface of
      commercial SnO2 (c-SnO2) by screen printing technology, and tested for gas
      sensing towards ethanol, benzene and hydrogen with operating temperatures ranging
      from 200  degrees C to 400  degrees C. Higher sensitivity was achieved by using
      the modified m-SnO2 layers on the c-SnO2 gas sensor, and it was found that the
      S(c/m2) sensor exhibited the highest response (Ra/Rg = 22.2) to 1000 ppm hydrogen
      at 400  degrees C. In this paper, the mechanism of the sensitivity and
      selectivity improvement of the gas sensors is also discussed.

PMID- 29036897
TI  - Inhibition of Starvation-Triggered Endoplasmic Reticulum Stress, Autophagy, and
      Apoptosis in ARPE-19 Cells by Taurine through Modulating the Expression of
      Calpain-1 and Calpain-2.
AB  - Age-related macular degeneration (AMD) is a complex disease with multiple
      initiators and pathways that converge on death for retinal pigment epithelial
      (RPE) cells. In this study, effects of taurine on calpains, autophagy,
      endoplasmic reticulum (ER) stress, and apoptosis in ARPE-19 cells (a human RPE
      cell line) were investigated. We first confirmed that autophagy, ER stress and
      apoptosis in ARPE-19 cells were induced by Earle's balanced salt solution (EBSS)
      through starvation to induce RPE metabolic stress. Secondly, inhibition of ER
      stress by 4-phenyl butyric acid (4-PBA) alleviated autophagy and apoptosis, and
      suppression of autophagy by 3-methyl adenine (3-MA) reduced the cell apoptosis,
      but the ER stress was minimally affected. Thirdly, the apoptosis, ER stress and
      autophagy were inhibited by gene silencing of calpain-2 and overexpression of
      calpain-1, respectively. Finally, taurine suppressed both the changes of the
      important upstream regulators (calpain-1 and calpain-2) and the activation of ER
      stress, autophagy and apoptosis, and taurine had protective effects on the
      survival of ARPE-19 cells. Collectively, this data indicate that taurine inhibits
      starvation-triggered endoplasmic reticulum stress, autophagy, and apoptosis in
      ARPE-19 cells by modulating the expression of calpain-1 and calpain-2.

PMID- 29036900
TI  - Toward a Robust Security Paradigm for Bluetooth Low Energy-Based Smart Objects in
      the Internet-of-Things.
AB  - Bluetooth Low Energy (BLE) has emerged as one of the most promising technologies
      to enable the Internet-of-Things (IoT) paradigm. In BLE-based IoT applications,
      e.g., wearables-oriented service applications, the Bluetooth MAC addresses of
      devices will be swapped for device pairings. The random address technique is
      adopted to prevent malicious users from tracking the victim's devices with
      stationary Bluetooth MAC addresses and accordingly the device privacy can be
      preserved. However, there exists a tradeoff between privacy and security in the
      random address technique. That is, when device pairing is launched and one device
      cannot actually identify another one with addresses, it provides an opportunity
      for malicious users to break the system security via impersonation attacks.
      Hence, using random addresses may lead to higher security risks. In this study,
      we point out the potential risk of using random address technique and then
      present critical security requirements for BLE-based IoT applications. To fulfill
      the claimed requirements, we present a privacy-aware mechanism, which is based on
      elliptic curve cryptography, for secure communication and access-control among
      BLE-based IoT objects. Moreover, to ensure the security of smartphone application
      associated with BLE-based IoT objects, we construct a Smart Contract-based
      Investigation Report Management framework (SCIRM) which enables smartphone
      application users to obtain security inspection reports of BLE-based applications
      of interest with smart contracts.

PMID- 29036901
TI  - Importance of Leadership Style towards Quality of Care Measures in Healthcare
      Settings: A Systematic Review.
AB  - Effective leadership of healthcare professionals is critical for strengthening
      quality and integration of care. This study aimed to assess whether there exist
      an association between different leadership styles and healthcare quality
      measures. The search was performed in the Medline (National Library of Medicine,
      PubMed interface) and EMBASE databases for the time period 2004-2015. The
      research question that guided this review was posed as: "Is there any
      relationship between leadership style in healthcare settings and quality of
      care?" Eighteen articles were found relevant to our research question. Leadership
      styles were found to be strongly correlated with quality care and associated
      measures. Leadership was considered a core element for a well-coordinated and
      integrated provision of care, both from the patients and healthcare
      professionals.

PMID- 29036899
TI  - Targeting Strategies for the Combination Treatment of Cancer Using Drug Delivery
      Systems.
AB  - Cancer cells have characteristics of acquired and intrinsic resistances to
      chemotherapy treatment-due to the hostile tumor microenvironment-that create a
      significant challenge for effective therapeutic regimens. Multidrug resistance,
      collateral toxicity to normal cells, and detrimental systemic side effects
      present significant obstacles, necessitating alternative and safer treatment
      strategies. Traditional administration of chemotherapeutics has demonstrated
      minimal success due to the non-specificity of action, uptake and rapid clearance
      by the immune system, and subsequent metabolic alteration and poor tumor
      penetration. Nanomedicine can provide a more effective approach to targeting
      cancer by focusing on the vascular, tissue, and cellular characteristics that are
      unique to solid tumors. Targeted methods of treatment using nanoparticles can
      decrease the likelihood of resistant clonal populations of cancerous cells. Dual
      encapsulation of chemotherapeutic drug allows simultaneous targeting of more than
      one characteristic of the tumor. Several first-generation, non-targeted
      nanomedicines have received clinical approval starting with Doxil(r) in 1995.
      However, more than two decades later, second-generation or targeted nanomedicines
      have yet to be approved for treatment despite promising results in pre-clinical
      studies. This review highlights recent studies using targeted nanoparticles for
      cancer treatment focusing on approaches that target either the tumor vasculature
      (referred to as 'vascular targeting'), the tumor microenvironment ('tissue
      targeting') or the individual cancer cells ('cellular targeting'). Recent studies
      combining these different targeting methods are also discussed in this review.
      Finally, this review summarizes some of the reasons for the lack of clinical
      success in the field of targeted nanomedicines.

PMID- 29036902
TI  - DNA Adducts Formed by Aristolochic Acid Are Unique Biomarkers of Exposure and
      Explain the Initiation Phase of Upper Urothelial Cancer.
AB  - Aristolochic acid (AA) is a plant alkaloid that causes aristolochic acid
      nephropathy (AAN) and Balkan endemic nephropathy (BEN), unique renal diseases
      frequently associated with upper urothelial cancer (UUC). This review summarizes
      the significance of AA-derived DNA adducts in the aetiology of UUC leading to
      specific A:T to T:A transversion mutations (mutational signature) in AAN/BEN
      associated tumours, which are otherwise rare in individuals with UCC not exposed
      to AA. Therefore, such DNA damage produced by AA-DNA adducts is one rare example
      of the direct association of exposure and cancer development (UUC) in humans,
      confirming that the covalent binding of carcinogens to DNA is causally related to
      tumourigenesis. Although aristolochic acid I (AAI), the major component of the
      natural plant extract AA, might directly cause interstitial nephropathy,
      enzymatic activation of AAI to reactive intermediates capable of binding to DNA
      is a necessary step leading to the formation of AA-DNA adducts and subsequently
      AA-induced malignant transformation. Therefore, AA-DNA adducts can not only be
      utilized as biomarkers for the assessment of AA exposure and markers of AA
      induced UUC, but also be used for the mechanistic evaluation of its enzymatic
      activation and detoxification. Differences in AA metabolism might be one of the
      reasons for an individual's susceptibility in the multi-step process of AA
      carcinogenesis and studying associations between activities and/or polymorphisms
      of the enzymes metabolising AA is an important determinant to identify
      individuals having a high risk of developing AA-mediated UUC.

PMID- 29036905
TI  - Extrinsic Calibration of Camera and 2D Laser Sensors without Overlap.
AB  - Extrinsic calibration of a camera and a 2D laser range finder (lidar) sensors is
      crucial in sensor data fusion applications; for example SLAM algorithms used in
      mobile robot platforms. The fundamental challenge of extrinsic calibration is
      when the camera-lidar sensors do not overlap or share the same field of view. In
      this paper we propose a novel and flexible approach for the extrinsic calibration
      of a camera-lidar system without overlap, which can be used for robotic platform
      self-calibration. The approach is based on the robot-world hand-eye calibration
      (RWHE) problem; proven to have efficient and accurate solutions. First, the
      system was mapped to the RWHE calibration problem modeled as the linear
      relationship AX = ZB , where X and Z are unknown calibration matrices. Then, we
      computed the transformation matrix B , which was the main challenge in the above
      mapping. The computation is based on reasonable assumptions about geometric
      structure in the calibration environment. The reliability and accuracy of the
      proposed approach is compared to a state-of-the-art method in extrinsic 2D lidar
      to camera calibration. Experimental results from real datasets indicate that the
      proposed approach provides better results with an L2 norm translational and
      rotational deviations of 314 mm and 0 . 12 ? respectively.

PMID- 29036903
TI  - Resveratrol and Amyloid-Beta: Mechanistic Insights.
AB  - The amyloid-beta (Abeta) hypothesis that dyshomeostasis between Abeta production
      and clearance is a very early, key molecular factor in the etiology of
      Alzheimer's disease (AD) has been proposed and examined in the AD research field.
      Scientists have focused on seeking natural products or drugs to influence the
      dynamic equilibrium of Abeta, targeting production and clearance of Abeta. There
      is emerging evidence that resveratrol (Res), a naturally occurring polyphenol
      mainly found in grapes and red wine, acts on AD in numerous in vivo and in vitro
      models. Res decreases the amyloidogenic cleavage of the amyloid precursor protein
      (APP), enhances clearance of amyloid beta-peptides, and reduces Abeta
      aggregation. Moreover, Res also protects neuronal functions through its
      antioxidant properties. This review discusses the action of Res on Abeta
      production, clearance and aggregation and multiple potential mechanisms,
      providing evidence of the useful of Res for AD treatment.

PMID- 29036904
TI  - Biopsychosocial Measures Related to Chronic Low Back Pain Postural Control in
      Older Adults.
AB  - This study examined the biopsychosocial measures related to postural control in
      the growing population of older adults (i.e., 60 years and older). The sample of
      the study consisted of 129 older adults (M = 74.45, SD = 6.95), with 34 males and
      95 females; 36 were classified with chronic low-back pain (CLBP), and 93 without
      chronic low-back pain (NCLBP). Physical and psychosocial constructs were analyzed
      as predictors for postural control measures. Additionally, gender and
      classification of low-back pain were examined as moderators for all physical and
      psychosocial measures. Results demonstrated that physical and psychosocial
      measures were able to significantly predict composite, visual, and vestibular
      balance measures, but not somatosensory or preference balance measures. The chair
      stand test, modified sit-and-reach test, sleep disturbance, and balance efficacy
      were all identified as individually significant predictors. Gender and CLBP did
      not moderate the utility of any predictor variables. Results of the current study
      re-confirm the importance of utilizing the biopsychosocial approach for future
      research examining postural control in older adults.

PMID- 29036906
TI  - From 2-Alkylsulfanylimidazoles to 2-Alkylimidazoles: An Approach towards
      Metabolically More Stable p38alpha MAP Kinase Inhibitors.
AB  - In vitro and in vivo metabolism studies revealed that 2-alkylsulfanylimidazole
      ML3403 (4-(5-(4-fluorophenyl)-2-(methylthio)-1H-imidazol-4-yl)-N-(1
      phenylethyl)pyridin-2-amine) undergoes rapid oxidation to the sulfoxide.
      Replacing the sulfur atom present in the two potent p38alpha mitogen-activated
      protein (MAP) kinase inhibitors ML3403 and LN950 (2-((5-(4-fluorophenyl)-4-(2-((3
      methylbutan-2-yl)amino)pyridin-4-yl)-1H-imidazol-2-yl)thio)ethan-1-ol) by a
      methylene group resulted in 2-alkylimidazole derivatives 1 and 2, respectively,
      having a remarkably improved metabolic stability. The 2-alkylimidazole analogs 1
      and 2 showed 20% and 10% biotransformation after 4 h of incubation with human
      liver microsomes, respectively. They display a 4-fold increased binding affinity
      towards the target kinase as well as similar in vitro potency and ex vivo
      efficacy relative to their 2-alkylsulfanylimidazole counterparts ML3403 and
      LN950. For example, 2-alkylimidazole 2, the analog of LN950, inhibits both the
      p38alpha MAP kinase as well as the LPS-stimulated tumor necrosis factor-alpha
      release from human whole blood in the low double-digit nanomolar range.

PMID- 29036908
TI  - Propofol Induces Apoptosis of Neurons but Not Astrocytes, Oligodendrocytes, or
      Neural Stem Cells in the Neonatal Mouse Hippocampus.
AB  - It has been shown that propofol can induce widespread apoptosis in neonatal mouse
      brains followed by long-term cognitive dysfunction. However, selective brain area
      and cell vulnerability to propofol remains unknown. This study was aimed to
      dissect toxic effect of propofol on multiple brain cells, including neurons,
      astrocytes, oligodendrocytes, and neural stem cells (NSCs). Seven-day-old mice
      were intraperitoneally administrated propofol or intralipid as a vehicle control
      for 6 hours. To identify vulnerable cells undergoing apoptosis following propofol
      exposure, brain sagittal sections were co-stained with antibodies against an
      apoptosis marker along with neuron, astrocyte, oligodendrocyte, or NSC markers
      using immunofluorescence staining. The results showed widespread apoptosis in
      propofol-treated brains (apoptotic cells: 1.55 +/- 0.04% and 0.06 +/- 0.01% in
      propofol group and intralipid-treated control group, respectively). Apoptotic
      cell distribution exhibits region- and cell-specific patterns. Several brain
      regions (e.g., cerebral cortex and hippocampus) were more vulnerable to propofol
      than other brain regions. Most apoptotic cells in the hippocampus were located in
      the cornus ammonis 1 (CA1) subfield. These apoptotic cells were only detected in
      neurons and not astrocytes, oligodendrocytes, or NSCs. These data demonstrate
      that different brain regions, subfields, and different types of neuronal cells in
      mice exhibit various vulnerabilities to propofol. Understanding region- and cell
      specific susceptibility to propofol will help to better understand cellular
      contribution to developmental neurotoxicity and further develop novel therapeutic
      targets.

PMID- 29036911
TI  - Comparison of Heavy-Duty Scuffing Behavior between Chromium-Based Ceramic
      Composite and Nickel-Chromium-Molybdenum-Coated Ring Sliding against Cast Iron
      Liner under Starvation.
AB  - A running-in and starved lubrication experiment is designed to investigate the
      heavy-duty scuffing behavior of piston ring coatings against cast iron (Fe)
      cylinder liner using the piston ring reciprocating liner test rig. The scuffing
      resistance of the piston ring with the chromium-based ceramic composite coating
      (CKS), and that with the thermally sprayed nickel-chromium-molybdenum coating
      (NCM) is compared at different nominal pressures (40~100 MPa) and temperatures
      (180~250  degrees C). With the failure time as a criterion, the rank order is as
      follows: NCM/Fe > CKS/Fe. Before the scoring occurs at the interface of the
      piston ring and cylinder liner (PRCL), the cast iron liner enters into a "polish
      wear" stage, and iron-based adhesive materials begin to form on the piston ring
      surface. With the macroscopic adhesion formation, the plastic shearing cycle
      causes surface damages mainly due to abrasive effects for the CKS/Fe pairs and
      adhesive effects for the NCM/Fe pairs.

PMID- 29036910
TI  - Melatonin Treatment Reduces Oxidative Damage and Normalizes Plasma Pro
      Inflammatory Cytokines in Patients Suffering from Charcot-Marie-Tooth Neuropathy:
      A Pilot Study in Three Children.
AB  - Charcot-Marie-Tooth neuropathy (CMT) is a motor and sensory neuropathy comprising
      a heterogeneous group of inherited diseases. The CMT1A phenotype is predominant
      in the 70% of CMT patients, with nerve conduction velocity reduction and
      hypertrophic demyelination. These patients have elevated oxidative stress and
      chronic inflammation. Currently, there is no effective cure for CMT; herein, we
      investigated whether melatonin treatment may reduce the inflammatory and
      oxidative damage in CMT1A patients. Three patients, aged 8-10 years, were treated
      with melatonin (60 mg at 21:00 h plus 10 mg at 09:00 h), and plasma levels of
      lipid peroxidation (LPO), nitrites (NOx), IL-1beta, IL-2, IL-6, TNF-alpha, INF
      gamma, oxidized to reduced glutathione (GSSG/GSH) ratio, and the activities of
      superoxide dismutase (SOD), glutathione-S transferase (GST), glutathione
      peroxidase (GPx), and reductase (GRd), were determined in erythrocytes at 3 and 6
      months of treatment. Healthy age- and sex-matched subjects were used as controls.
      The results showed increased activities of SOD, GST, GPx, and GRd in CMT1A
      patients, which were reduced at 3 and 6 months of treatment. The GSSG/GSH ratio
      significantly increased in the patients, returning to control values after
      melatonin treatment. The inflammatory process was confirmed by the elevation of
      all proinflammatory cytokines measured, which were also normalized by melatonin.
      LPO and NOx, which also were elevated in the patients, were normalized by
      melatonin. The results document beneficial effects of the use of melatonin in
      CMT1A patients to reduce the hyperoxidative and inflammatory condition, which may
      correlate with a reduction of the degenerative process.

PMID- 29036912
TI  - Caustic Ingestion in the Elderly: Influence of Age on Clinical Outcome.
AB  - Caustic poisonings are still associated with many fatalities. Studies focusing on
      the elderly are rare. The purpose of the present study was to compare the
      clinical outcomes of caustic ingestion injury in elderly and non-elderly adults
      with regard to gender, intent of exposure, substance ingested, severity of
      mucosal injury, complications, and mortality. Caustic substance exposures
      reported to the National Toxicological Information Centre in Slovakia during 1998
      2015 were reviewed retrospectively. The patients were divided into two groups:
      the non-elderly (<60 years) and elderly adults (>=60 years). The mortality rate
      in the elderly was significantly higher (elderly 23.0% vs. non-elderly 11.3%; p =
      0.041). The risk of fatal outcome in the elderly was increased by acid ingestion
      (OR = 7.822; p = 0.002), particularly hydrochloric acid (OR = 5.714, p = 0.006).
      The incidence of respiratory complications was almost two times higher in the
      elderly was 31.1% vs. 17.4% for the non-elderly (p = 0.037). Respiratory
      complications significantly correlated with an increased mortality rate (p =
      0.001) in the elderly whereas there was no association between GI complications
      and mortality in the elderly (p = 0.480). Elderly patients with respiratory
      complications had the poorest clinical outcomes. The highest risk of
      complications and fatalities was observed in patients after hydrochloric acid
      ingestion.

PMID- 29036909
TI  - Diabetes-Induced Dysfunction of Mitochondria and Stem Cells in Skeletal Muscle
      and the Nervous System.
AB  - Diabetes mellitus is one of the most common metabolic diseases spread all over
      the world, which results in hyperglycemia caused by the breakdown of insulin
      secretion or insulin action or both. Diabetes has been reported to disrupt the
      functions and dynamics of mitochondria, which play a fundamental role in
      regulating metabolic pathways and are crucial to maintain appropriate energy
      balance. Similar to mitochondria, the functions and the abilities of stem cells
      are attenuated under diabetic condition in several tissues. In recent years,
      several studies have suggested that the regulation of mitochondria functions and
      dynamics is critical for the precise differentiation of stem cells. Importantly,
      physical exercise is very useful for preventing the diabetic alteration by
      improving the functions of both mitochondria and stem cells. In the present
      review, we provide an overview of the diabetic alterations of mitochondria and
      stem cells and the preventive effects of physical exercise on diabetes, focused
      on skeletal muscle and the nervous system. We propose physical exercise as a
      countermeasure for the dysfunction of mitochondria and stem cells in several
      target tissues under diabetes complication and to improve the physiological
      function of patients with diabetes, resulting in their quality of life being
      maintained.

PMID- 29036907
TI  - A Functional Interplay between IGF-1 and Adiponectin.
AB  - A functional relationship is suggested between two well-known protein hormones,
      insulin-like growth factor 1 (IGF-1) and adiponectin. In the last two decades in
      fact, different experimental evidence has indicated a non-random link between
      them. Here, we describe briefly the IGF-1 and adiponectin systems, and we then
      focus on their putative interplay in relation to several pathological conditions,
      including obesity, diabetes, insulin resistance, cardiovascular disease, and
      cancer. Although the existing studies are hardly comparable, they definitely
      indicate a functional connection between these two protein hormones. In
      conclusion, the current knowledge strongly encourages further research into the
      common, as well as novel, mechanisms through which IGF-1 and adiponectin exert
      their concerted action.

PMID- 29036913
TI  - Alpha-Galacto-Oligosaccharides at Low Dose Improve Liver Steatosis in a High-Fat
      Diet Mouse Model.
AB  - Non-Alcoholic Fatty Liver Disease (NAFLD) is the major liver disease worldwide
      and is linked to the development of metabolic syndrome and obesity. As alpha
      galacto-oligosaccharides (alpha-GOS) from legumes have been shown to reduce body
      weight and hyperphagia in overweight adults, it was hypothesized that they would
      exert benefits on the development of metabolic syndrome and associated NAFLD in a
      rodent model. C57Bl/6J mice were fed a high-fat diet until they developed
      metabolic syndrome and were then orally treated either with alpha-GOS at a
      physiological dose (2.2 g/kg BW/d) or the vehicle over 7 weeks. alpha-GOS induced
      a reduction in food intake, but without affecting body weight during the first
      week of treatment, when compared to the vehicle. Fasting glycaemia was improved
      after 4 weeks of treatment with alpha-GOS, whereas insulin sensitivity (assessed
      with HOMA-IR) was unaffected at the end of the experiment. Plasma non-esterified
      fatty acids, low-density lipoprotein (LDL) and total cholesterol were lowered by
      alpha-GOS while high-density lipoprotein (HDL) and triglycerides levels remained
      unaffected. alpha-GOS markedly improved liver steatosis as well as free fatty
      acid and triglyceride accumulation in the liver. alpha-GOS improved plasma lipids
      and prevented NAFLD development through mechanisms which are independent of body
      weight management and glycemic control.

PMID- 29036914
TI  - Molecular Characterization and Functional Analysis of a Ferritin Heavy Chain
      Subunit from the Eri-Silkworm, Samia cynthia ricini.
AB  - Ferritins are conserved iron-binding proteins that are primarily involved in iron
      storage, detoxification and the immune response. Despite the importance of
      ferritin in organisms, little is known about their roles in the eri-silkworm
      (Samia cynthia ricini). We previously identified a ferritin heavy chain subunit
      named ScFerHCH in the S. c. ricini transcriptome database. The full-length S. c.
      ricini ferritin heavy chain subunit (ScFerHCH) was 1863 bp and encoded a protein
      of 231 amino acids with a deduced molecular weight of 25.89 kDa. Phylogenetic
      analysis revealed that ScFerHCH shared a high amino acid identity with the Bombyx
      mori and Danaus plexippus heavy chain subunits. Higher ScFerHCH expression levels
      were found in the silk gland, fat body and midgut of S. c. ricini by reverse
      transcription quantitative polymerase chain reaction (RT-qPCR) and Western
      blotting. Injection of Staphylococcus aureus and Pseudomonas aeruginosa was
      associated with an upregulation of ScFerHCH in the midgut, fat body and
      hemolymph, indicating that ScFerHCH may contribute to the host's defense against
      invading pathogens. In addition, the anti-oxidation activity and iron-binding
      capacity of recombinant ScFerHCH protein were examined. Taken together, our
      results suggest that the ferritin heavy chain subunit from eri-silkworm may play
      critical roles not only in innate immune defense, but also in organismic iron
      homeostasis.

PMID- 29036917
TI  - The Effect of TiO2 Doped Photocatalytic Nano-Additives on the Hydration and
      Microstructure of Portland and High Alumina Cements.
AB  - Mortars with two different binders (Portland cement (PC) and high alumina cement
      (HAC)) were modified upon the bulk incorporation of nano-structured
      photocatalytic additives (bare TiO2, and TiO2 doped with either iron (Fe-TiO2) or
      vanadium (V-TiO2)). Plastic and hardened state properties of these mortars were
      assessed in order to study the influence of these nano-additives. Water demand
      was increased, slightly by bare TiO2 and Fe-TiO2, and strongly by V-TiO2, in
      agreement with the reduction of the particle size and the tendency to
      agglomerate. Isothermal calorimetry showed that hydration of the cementitious
      matrices was accelerated due to additional nucleation sites offered by the nano
      additives. TiO2 and doped TiO2 did not show pozzolanic reactivity in the binding
      systems. Changes in the pore size distribution, mainly the filler effect of the
      nano-additives, accounted for the increase in compressive strengths measured for
      HAC mortars. A complex microstructure was seen in calcium aluminate cement
      mortars, strongly dependent on the curing conditions. Fe-TiO2 was found to be
      homogeneously distributed whereas the tendency of V-TiO2 to agglomerate was
      evidenced by elemental distribution maps. Water absorption capacity was not
      affected by the nano-additive incorporation in HAC mortars, which is a favourable
      feature for the application of these mortars.

PMID- 29036915
TI  - STAT3 but Not HIF-1alpha Is Important in Mediating Hypoxia-Induced
      Chemoresistance in MDA-MB-231, a Triple Negative Breast Cancer Cell Line.
AB  - Hypoxia-induced chemoresistance (HICR) is a well-recognized phenomenon, and in
      many experimental models, hypoxia inducible factor-1alpha (HIF-1alpha) is
      believed to be a key player. We aimed to better understand the mechanism
      underlying HICR in a triple negative breast cancer cell line, MDA-MB-231, with a
      focus on the role of HIF-1alpha. In this context, the effect of hypoxia on the
      sensitivity of MDA-MB-231 cells to cisplatin and their stem-like features was
      evaluated and the role of HIF-1alpha in both phenomena was assessed. Our results
      showed that hypoxia significantly increased MDA-MB-231 resistance to cisplatin.
      Correlating with this, intracellular uptake of cisplatin was significantly
      reduced under hypoxia. Furthermore, the stem-like features of MDA-MB-231 cells
      increased as evidenced by the significant increases in the expression of ATP
      binding cassette (ABC) drug transporters, the proportion of CD44+/CD24- cells,
      clonogenic survival and cisplatin chemoresistance. Under hypoxia, both the
      protein level and DNA binding of HIF-1alpha was dramatically increased.
      Surprisingly, siRNA knockdown of HIF-1alpha did not result in an appreciable
      change to HICR. Instead, signal transducer and activator of transcription 3
      (STAT3) activation was found to be important. STAT3 activation may confer HICR by
      upregulating ABC transporters, particularly ABCC2 and ABCC6. This study has
      demonstrated that, in MDA-MB-231 cells, STAT3 rather than HIF-1alpha is important
      in mediating HICR to cisplatin.

PMID- 29036916
TI  - Recent Progresses and Development of Advanced Atomic Layer Deposition towards
      High-Performance Li-Ion Batteries.
AB  - Electrode materials and electrolytes play a vital role in device-level
      performance of rechargeable Li-ion batteries (LIBs). However, electrode
      structure/component degeneration and electrode-electrolyte sur-/interface
      evolution are identified as the most crucial obstacles in practical applications.
      Thanks to its congenital advantages, atomic layer deposition (ALD) methodology
      has attracted enormous attention in advanced LIBs. This review mainly focuses
      upon the up-to-date progress and development of the ALD in high-performance LIBs.
      The significant roles of the ALD in rational design and fabrication of multi
      dimensional nanostructured electrode materials, and finely tailoring electrode
      electrolyte sur-/interfaces are comprehensively highlighted. Furthermore, we
      clearly envision that this contribution will motivate more extensive and
      insightful studies in the ALD to considerably improve Li-storage behaviors.
      Future trends and prospects to further develop advanced ALD nanotechnology in
      next-generation LIBs were also presented.

PMID- 29036918
TI  - Regulation of the Electroanalytical Performance of Ultrathin Titanium Dioxide
      Nanosheets toward Lead Ions by Non-Metal Doping.
AB  - Three non-metallic elements, sulfur, fluorine, and iodine, were used to dope the
      ultrathin two-dimensional TiO2 nanosheets, which would regulate their
      electroanalytical properties toward heavy metal ions. Among these doped
      materials, fluorine-doped TiO2 nanosheets shows the highest electrochemical
      sensitivity and a superior detection limit toward Pb(II) when the doping
      concentration is 10%. When compared with the bare TiO2 nanosheets, the
      sensitivity increased by 102%, and the detection limit decreased by 36.4%.
      Through combining further electrochemical experiments and density-functional
      theory calculations, the enhanced electrochemical performance stemming from
      element doping was then investigated in detail. The theoretical calculation
      demonstrated that fluorine doping could greatly increase the adsorption energy of
      Pb(II) on the TiO2 nanosheets and enhance their loading capacity. Both cyclic
      voltammetric and electrical impedance spectroscopy analysis indicated the
      enhanced electron transfer rate on the electrode modified by fluorine-doped TiO2
      nanosheets. Further measurement on the desorption performance showed the better
      stripping response of Pb(II) on the electrode with TiO2 nanosheets after fluorine
      doping, which suggests that fluorine doping is beneficial for Pb(II) diffuse onto
      the electrode surface for the reduction and stripping reaction. Therefore, the
      element doping of two-dimensional TiO2 nanosheets provides a facile method to
      extend the electronic materials toward detection of heavy metal ions in the
      environment.

PMID- 29036919
TI  - A Two-Step Bioconversion Process for Canolol Production from Rapeseed Meal
      Combining an Aspergillus niger Feruloyl Esterase and the Fungus Neolentinus
      lepideus.
AB  - Rapeseed meal is a cheap and abundant raw material, particularly rich in phenolic
      compounds of biotechnological interest. In this study, we developed a two-step
      bioconversion process of naturally occurring sinapic acid (4-hydroxy-3,5
      dimethoxycinnamic acid) from rapeseed meal into canolol by combining the
      complementary potentialities of two filamentous fungi, the micromycete
      Aspergillus niger and the basidiomycete Neolentinus lepideus. Canolol could
      display numerous industrial applications because of its high antioxidant,
      antimutagenic and anticarcinogenic properties. In the first step of the process,
      the use of the enzyme feruloyl esterase type-A (named AnFaeA) produced with the
      recombinant strain A. niger BRFM451 made it possible to release free sinapic acid
      from the raw meal by hydrolysing the conjugated forms of sinapic acid in the meal
      (mainly sinapine and glucopyranosyl sinapate). An amount of 39 nkat AnFaeA per
      gram of raw meal, at 55  degrees C and pH 5, led to the recovery of 6.6 to 7.4 mg
      of free sinapic acid per gram raw meal, which corresponded to a global hydrolysis
      yield of 68 to 76% and a 100% hydrolysis of sinapine. Then, the XAD2 adsorbent (a
      styrene and divinylbenzene copolymer resin), used at pH 4, enabled the efficient
      recovery of the released sinapic acid, and its concentration after elution with
      ethanol. In the second step, 3-day-old submerged cultures of the strain N.
      lepideus BRFM15 were supplied with the recovered sinapic acid as the substrate of
      bioconversion into canolol by a non-oxidative decarboxylation pathway. Canolol
      production reached 1.3 g/L with a molar yield of bioconversion of 80% and a
      productivity of 100 mg/L day. The same XAD2 resin, when used at pH 7, allowed the
      recovery and purification of canolol from the culture broth of N. lepideus. The
      two-step process used mild conditions compatible with green chemistry.

PMID- 29036920
TI  - Evaluation of MC3T3 Cells Proliferation and Drug Release Study from Sodium
      Hyaluronate-1,4-butanediol Diglycidyl Ether Patterned Gel.
AB  - A pattern gel has been fabricated using sodium hyaluronate (HA) and 1,4
      butanediol diglycidyl ether (BDDGE) through the micro-molding technique. The
      cellular behavior of osteoblast cells (MC3T3) in the presence and absence of
      dimethyloxalylglycine (DMOG) and sodium borate (NaB) in the pattern gel (HA
      BDDGE) has been evaluated for its potential application in bone regeneration. The
      Fourier transform infrared spectroscopy (FTIR), 13C-nuclear magnetic resonance
      spectroscopy (13C NMR), and thermogravimetric analysis (TGA) results implied the
      crosslinking reaction between HA and BDDGE. The scanning electron microscopy
      (SEM) analysis confirmed the formation of pattern on the surface of HA-BDDGE. The
      gel property of the crosslinked HA-BDDGE has been investigated by swelling study
      in distilled water at 37  degrees C. The HA-BDDGE gel releases DMOG in a
      controlled way for up to seven days in water at 37  degrees C. The synthesized
      gel is biocompatible and the bolus drug delivery results indicated that the DMOG
      containing patterned gel demonstrates a better cell migration ability on the
      surface than NaB. For local delivery, the pattern gel with 300 uM NaB or 300 uM
      DMOG induced cell clusters formation, and the gel with 150 uM NaB/DMOG showed
      high cell proliferation capability only. The vital role of NaB for bone
      regeneration has been endorsed from the formation of cell clusters in presence of
      NaB in the media. The in vitro results indicated that the pattern gel showed
      angiogenic and osteogenic responses with good ALP activity and enhanced HIF
      1alpha, and Runx2 levels in the presence of DMOG and NaB in MC3T3 cells. Hence,
      the HA-BDDGE gel could be used in bone regeneration application.

PMID- 29036921
TI  - Transformation of CuO Nanoparticles in the Aquatic Environment: Influence of pH,
      Electrolytes and Natural Organic Matter.
AB  - Many studies have shown the effect of solution chemistry on the environmental
      behavior of metal-based nanoparticles (NPs), except CuO NPs. Here, we
      investigated the agglomeration, sedimentation, dissolution, and speciation of CuO
      NPs by varying pH, ionic strength, ionic valence, and natural organic matter
      (NOM). The results showed that as the pH moved away from 6, the size of CuO
      agglomerates decreased, along with the enhanced NP suspension stabilization, due
      to the increase of electrostatic repulsive force. Increasing ionic strength and
      valence intensified the agglomeration and sedimentation of CuO NPs because of the
      compression of electrical double layers. The presence of humic acid and citric
      acid enhanced the dispersion and stabilization of CuO NP suspension, but l
      cysteine showed a different impact. Decreasing pH, increasing ionic strength and
      all NOM improved the dissolution of CuO NPs, but the divalent electrolyte (CaCl2)
      inhibited the Cu2+ release from CuO NPs compared to the monovalent electrolyte
      (NaCl). In addition, X-ray absorption near edge structure (XANES) analysis
      demonstrated that the presence of l-cysteine transformed more than 30% of CuO NPs
      to Cu(I)-cysteine by coordinating with thiol group. This study can give us an in
      depth understanding on the environmental behavior and fate of CuO NPs in the
      aquatic environment.

PMID- 29036923
TI  - Environmental Impact and Relative Invasiveness of Free-Roaming Domestic
      Carnivores-a North American Survey of Governmental Agencies.
AB  - A survey of the United States and Canadian governmental agencies investigated the
      environmental impact and relative invasiveness of free-roaming domestic non
      native carnivores-dogs, cats, and ferrets. Agencies represented wildlife, fish,
      game, natural or environmental resources, parks and recreation, veterinary and
      human health, animal control, and agriculture. Respondents were asked to document
      the number and frequency of sightings of unconfined animals, evidence for
      environmental harm, and the resulting "degree of concern" in their respective
      jurisdictions. Results confirmed the existence of feral (breeding) cats and dogs,
      documenting high levels of concern regarding the impact of these animals on both
      continental and surrounding insular habitats. Except for occasional strays, no
      free-roaming or feral ferrets were reported; nor were there reports of ferrets
      impacting native wildlife, including ground-nesting birds, or sensitive species.
      This is the first study to report the relative impact of free-roaming domestic
      carnivores. Dogs and cats meet the current definition of "invasive" species,
      whereas ferrets do not. Differences in how each species impacts the North
      American environment highlights the complex interaction between non-native
      species and their environment. Public attitudes and perceptions regarding these
      species may be a factor in their control and agency management priorities.

PMID- 29036924
TI  - Bio-Inspired Distributed Transmission Power Control Considering QoS Fairness in
      Wireless Body Area Sensor Networks.
AB  - Recently, the development of wireless body area sensor network (WBASN) has
      accelerated due to the rapid development of wireless technology. In the WBASN
      environment, many WBASNs coexist where communication ranges overlap with each
      other, resulting in the possibility of interference. Although nodes in a WBASN
      typically operate at a low power level, to avoid adversely affecting the human
      body, high transmission rates may be required to support some applications. In
      addition to this, since many varieties of applications exist in the WBASN
      environment, each prospective user may have different quality of service (QoS)
      requirements. Hence, the following issues should be considered in the WBASN
      environment: (1) interference between adjacent WBASNs, which influences the
      performance of a specific system, and (2) the degree of satisfaction on the QoS
      of each user, i.e., the required QoS such as user throughput should be considered
      to ensure that all users in the network are provided with a fair QoS
      satisfaction. Thus, in this paper, we propose a transmission power adjustment
      algorithm that addresses interference problems and guarantees QoS fairness
      between users. First, we use a new utility function to measure the degree of the
      satisfaction on the QoS for each user. Then, the transmission power of each
      sensor node is calculated using the Cucker-Smale model, and the QoS satisfaction
      of each user is synchronized dispersively. The results of simulations show that
      the proposed algorithm performs better than existing algorithms, with respect to
      QoS fairness and energy efficiency.

PMID- 29036922
TI  - MicroRNA and mRNA Dysregulation in Astrocytes Infected with Zika Virus.
AB  - The Zika virus (ZIKV) epidemic is an ongoing public health concern. ZIKV is a
      flavivirus reported to be associated with microcephaly, and recent work in animal
      models demonstrates the ability of the virus to cross the placenta and affect
      fetal brain development. Recent findings suggest that the virus preferentially
      infects neural stem cells and thereby deregulates gene expression, cell cycle
      progression, and increases cell death. However, neuronal stem cells are not the
      only brain cells that are susceptible to ZIKV and infection of other brain cells
      may contribute to disease progression. Herein, we characterized ZIKV replication
      in astrocytes, and profiled temporal changes in host microRNAs (miRNAs) and
      transcriptomes during infection. We observed the deregulation of numerous
      processes known to be involved in flavivirus infection, including genes involved
      in the unfolded protein response pathway. Moreover, a number of miRNAs were
      upregulated, including miR-30e-3p, miR-30e-5p, and, miR-17-5p, which have been
      associated with other flavivirus infections. This study highlights potential
      miRNAs that may be of importance in ZIKV pathogenesis.

PMID- 29036925
TI  - Evaluating Oilseed Biofuel Production Feasibility in California's San Joaquin
      Valley Using Geophysical and Remote Sensing Techniques.
AB  - Though more costly than petroleum-based fuels and a minor component of overall
      military fuel sources, biofuels are nonetheless strategically valuable to the
      military because of intentional reliance on multiple, reliable, secure fuel
      sources. Significant reduction in oilseed biofuel cost occurs when grown on
      marginally productive saline-sodic soils plentiful in California's San Joaquin
      Valley (SJV). The objective is to evaluate the feasibility of oilseed production
      on marginal soils in the SJV to support a 115 ML yr-1 biofuel conversion
      facility. The feasibility evaluation involves: (1) development of an Ida Gold
      mustard oilseed yield model for marginal soils; (2) identification of marginally
      productive soils; (3) development of a spatial database of edaphic factors
      influencing oilseed yield and (4) performance of Monte Carlo simulations showing
      potential biofuel production on marginally productive SJV soils. The model
      indicates oilseed yield is related to boron, salinity, leaching fraction, and
      water content at field capacity. Monte Carlo simulations for the entire SJV fit a
      shifted gamma probability density function: Q = 68.986 + gamma (6.134,5.285),
      where Q is biofuel production in ML yr-1. The shifted gamma cumulative density
      function indicates a 0.15-0.17 probability of meeting the target biofuel
      production level of 115 ML yr-1, making adequate biofuel production unlikely.

PMID- 29036926
TI  - Evaluation of Sensible Heat Flux and Evapotranspiration Estimates Using a Surface
      Layer Scintillometer and a Large Weighing Lysimeter.
AB  - Accurate estimates of actual crop evapotranspiration (ET) are important for
      optimal irrigation water management, especially in arid and semi-arid regions.
      Common ET sensing methods include Bowen Ratio, Eddy Covariance (EC), and
      scintillometers. Large weighing lysimeters are considered the ultimate standard
      for measurement of ET, however, they are expensive to install and maintain.
      Although EC and scintillometers are less costly and relatively portable, EC has
      known energy balance closure discrepancies. Previous scintillometer studies used
      EC for ground-truthing, but no studies considered weighing lysimeters. In this
      study, a Surface Layer Scintillometer (SLS) was evaluated for accuracy in
      determining ET as well as sensible and latent heat fluxes, as compared to a large
      weighing lysimeter in Bushland, TX. The SLS was installed over irrigated grain
      sorghum (Sorghum bicolor (L.) Moench) for the period 29 July-17 August 2015 and
      over grain corn (Zea mays L.) for the period 23 June-2 October 2016. Results
      showed poor correlation for sensible heat flux, but much better correlation with
      ET, with r2 values of 0.83 and 0.87 for hourly and daily ET, respectively. The
      accuracy of the SLS was comparable to other ET sensing instruments with an RMSE
      of 0.13 mm.h-1 (31%) for hourly ET; however, summing hourly values to a daily
      time step reduced the ET error to 14% (0.75 mm.d-1). This level of accuracy
      indicates that potential exists for the SLS to be used in some water management
      applications. As few studies have been conducted to evaluate the SLS for ET
      estimation, or in combination with lysimetric data, further evaluations would be
      beneficial to investigate the applicability of the SLS in water resources
      management.

PMID- 29036928
TI  - Plasma miR-155, miR-203, and miR-205 are Biomarkers for Monitoring of Primary
      Cutaneous T-Cell Lymphomas.
AB  - Primary cutaneous T-cell lymphomas (CTCL) affect the skin and tend to transform
      and spread. CTCL involves primarily the Mycosis fungoides (MF) and more
      aggressive Sezary syndrome (SS). Oncogenic microRNAs (miRs) are stable epigenetic
      inhibitors often deregulated in the tumour and detectable as biomarkers in non
      cellular fractions of peripheral blood. The tumour-specific expression of miR
      155, miR-203, and miR-205 was shown to correctly diagnose CTCL. We herein asked
      whether these microRNAs can be used as plasma biomarkers for clinical CTCL
      monitoring. Patients with CTCL (n = 10) and controls with non-malignant
      conditions (n = 11) repeatedly donated plasma samples every ca. five months.
      MicroRNAs were detected in the plasma samples by specifically-primed RT-PCR
      followed by multivariate analyses of the miR expression dynamics. We herein
      established the plasma miR-classifier for detecting CTCL based on the miR-155
      upregulation and miR-203/miR-205 downregulation with 100% specificity and 94%
      sensitivity. The 3-miR-score in the consecutive samples coincided with the
      clinical outcome of MF and SS patients such as the therapy response or changes in
      the clinical stage or tumor size. Quantitation of the selected microRNAs in
      plasma is a specific and straightforward approach for evaluating CTCL outcome
      representing, thus, a valuable tool for CTCL diagnostics and therapy response
      monitoring.

PMID- 29036927
TI  - Chinese Olive (Canarium album L.) Fruit Extract Attenuates Metabolic Dysfunction
      in Diabetic Rats.
AB  - Hyperglycemia and dysregulation of lipid metabolism play a crucial role in
      metabolic dysfunction. The aims of present study were to evaluate the
      ameliorative effect of the ethyl acetate fraction of Chinese olive fruit extract
      (CO-EtOAc) on high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic rats.
      CO-EtOAc, rich in gallic acid and ellagic acid, could markedly decreased the body
      weight and epididymal adipose mass. In addition, CO-EtOAc increased serum HDL-C
      levels, hepatic GSH levels, and antioxidant enzyme activities; lowered blood
      glucose, serum levels of total cholesterol (TC), triglycerides (TG), bile acid,
      and tumor necrosis factor alpha (TNFalpha); and reduced TC and TG in liver. We
      further demonstrated that CO-EtOAc mildly suppressed hepatic levels of
      phosphorylated IRS-1, TNF-alpha, and IL-6, but enhanced Akt phosphorylation. The
      possible mechanisms of cholesterol metabolism were assessed by determining the
      expression of genes involved in cholesterol transportation, biosynthesis, and
      degradation. It was found that CO-EtOAc not only inhibited mRNA levels of SREBP
      2, HMG-CoAR, SR-B1, and CYP7A1 but also increased the expression of genes, such
      as ABCA1 and LDLR that governed cholesterol efflux and cholesterol uptake.
      Moreover, the protein expressions of ABCA1 and LDLR were also significantly
      increased in the liver of rats supplemented with CO-EtOAc. We suggest that
      Chinese olive fruit may ameliorate metabolic dysfunction in diabetic rats under
      HFD challenge.

PMID- 29036930
TI  - Automatic Hotspot and Sun Glint Detection in UAV Multispectral Images.
AB  - Last advances in sensors, photogrammetry and computer vision have led to high
      automation levels of 3D reconstruction processes for generating dense models and
      multispectral orthoimages from Unmanned Aerial Vehicle (UAV) images. However,
      these cartographic products are sometimes blurred and degraded due to sun
      reflection effects which reduce the image contrast and colour fidelity in
      photogrammetry and the quality of radiometric values in remote sensing
      applications. This paper proposes an automatic approach for detecting sun
      reflections problems (hotspot and sun glint) in multispectral images acquired
      with an Unmanned Aerial Vehicle (UAV), based on a photogrammetric strategy
      included in a flight planning and control software developed by the authors. In
      particular, two main consequences are derived from the approach developed: (i)
      different areas of the images can be excluded since they contain sun reflection
      problems; (ii) the cartographic products obtained (e.g., digital terrain model,
      orthoimages) and the agronomical parameters computed (e.g., normalized vegetation
      index-NVDI) are improved since radiometric defects in pixels are not considered.
      Finally, an accuracy assessment was performed in order to analyse the error in
      the detection process, getting errors around 10 pixels for a ground sample
      distance (GSD) of 5 cm which is perfectly valid for agricultural applications.
      This error confirms that the precision in the detection of sun reflections can be
      guaranteed using this approach and the current low-cost UAV technology.

PMID- 29036929
TI  - Interaction between Rho GTPases and 14-3-3 Proteins.
AB  - The Rho GTPase family accounts for as many as 20 members. Among them, the
      archetypes RhoA, Rac1, and Cdc42 have been the most well-characterized. Like all
      members of the small GTPases superfamily, Rho proteins act as molecular switches
      to control cellular processes by cycling between active, GTP-bound and inactive,
      GDP-bound states. The 14-3-3 family proteins comprise seven isoforms. They exist
      as dimers (homo- or hetero-dimer) in cells. They function by binding to Ser/Thr
      phosphorylated intracellular proteins, which alters the conformation, activity,
      and subcellular localization of their binding partners. Both 14-3-3 proteins and
      Rho GTPases regulate cell cytoskeleton remodeling and cell migration, which
      suggests a possible interaction between the signaling pathways regulated by these
      two groups of proteins. Indeed, more and more emerging evidence indicates the
      mutual regulation of these two signaling pathways. There have been many
      documented reviews of 14-3-3 protein and Rac1 separately, but there is no review
      regarding the interaction and mutual regulation of these two groups of proteins.
      Thus, in this article we thoroughly review all the reported interactions between
      the signaling pathways regulated by 14-3-3 proteins and Rho GTPases (mostly
      Rac1).

PMID- 29036931
TI  - Mass Spectrometric Studies of Apolipoprotein Proteoforms and Their Role in Lipid
      Metabolism and Type 2 Diabetes.
AB  - Apolipoproteins function as structural components of lipoprotein particles,
      cofactors for enzymes, and ligands for cell-surface receptors. Most of the
      apoliporoteins exhibit proteoforms, arising from single nucleotide polymorphisms
      (SNPs) and post-translational modifications such as glycosylation, oxidation, and
      sequence truncations. Reviewed here are recent studies correlating
      apolipoproteins proteoforms with the specific clinical measures of lipid
      metabolism and cardiometabolic risk. Targeted mass spectrometric immunoassays
      toward apolipoproteins A-I, A-II, and C-III were applied on large cross-sectional
      and longitudinal clinical cohorts. Several correlations were observed, including
      greater apolipoprotein A-I and A-II oxidation in patients with diabetes and
      cardiovascular disease, and a divergent apoC-III proteoforms association with
      plasma triglycerides, indicating significant differences in the metabolism of the
      individual apoC-III proteoforms. These are the first studies of their kind,
      correlating specific proteoforms with clinical measures in order to determine
      their utility as potential clinical biomarkers for disease diagnosis, risk
      stratification, and therapy decisions. Such studies provide the impetus for the
      further development and clinical translation of MS-based protein tests.

PMID- 29036932
TI  - Electrospun Chitosan-Gelatin Biopolymer Composite Nanofibers for Horseradish
      Peroxidase Immobilization in a Hydrogen Peroxide Biosensor.
AB  - A biosensor based on chitosan-gelatin composite biopolymers nanofibers is found
      to be effective for the immobilization of horseradish peroxidase to detect
      hydrogen peroxide. The biopolymer nanofibers were fabricated by an electrospining
      technique. Upon optimization of synthesis parameters, biopolymers nanofibers, an
      average of 80 nm in diameter, were obtained and were then modified on the working
      electrode surface. The effects of the concentration of enzyme, pH, and
      concentration of the buffer and the working potential on the current response of
      the nanofibers-modified electrode toward hydrogen peroxide were optimized to
      obtain the maximal current response. The results found that horseradish
      peroxidase immobilization on chitosan-gelatin composite biopolymer nanofibers had
      advantages of fast response, excellent reproducibility, high stability, and
      showed a linear response to hydrogen peroxide in the concentration range from 0.1
      to 1.7 mM with a detection limit of 0.05 mM and exhibited high sensitivity of 44
      uA?mM-1?cm-2. The developed system was evaluated for analysis of disinfectant
      samples and showed good agreement between the results obtained by the titration
      method without significant differences at the 0.05 significance level. The
      proposed strategy based on chitosan-gelatin composite biopolymer nanofibers for
      the immobilization of enzymes can be extended for the development of other enzyme
      based biosensors.

PMID- 29036933
TI  - School Leadership and Cyberbullying-A Multilevel Analysis.
AB  - Cyberbullying is a relatively new form of bullying, with both similarities and
      differences to traditional bullying. While earlier research has examined
      associations between school-contextual characteristics and traditional bullying,
      fewer studies have focused on the links to students' involvement in cyberbullying
      behavior. The aim of the present study is to assess whether school-contextual
      conditions in terms of teachers' ratings of the school leadership are associated
      with the occurrence of cyberbullying victimization and perpetration among
      students. The data are derived from two separate data collections performed in
      2016: The Stockholm School Survey conducted among students in the second grade of
      upper secondary school (ages 17-18 years) in Stockholm municipality, and the
      Stockholm Teacher Survey which was carried out among teachers in the same
      schools. The data include information from 6067 students distributed across 58
      schools, linked with school-contextual information based on reports from 1251
      teachers. Cyberbullying victimization and perpetration are measured by students'
      self-reports. Teachers' ratings of the school leadership are captured by an index
      based on 10 items; the mean value of this index was aggregated to the school
      level. Results from binary logistic multilevel regression models show that high
      teacher ratings of the school leadership are associated with less cyberbullying
      victimization and perpetration. We conclude that a strong school leadership
      potentially prevents cyberbullying behavior among students.

PMID- 29036935
TI  - Laser Powder Cladding of Ti-6Al-4V alpha/beta Alloy.
AB  - Laser cladding process was performed on a commercial Ti-6Al-4V (alpha + beta)
      titanium alloy by means of tungsten carbide-nickel based alloy powder blend.
      Nd:YAG laser with a 2.2-KW continuous wave was used with coaxial jet nozzle
      coupled with a standard powder feeding system. Four-track deposition of a blended
      powder consisting of 60 wt % tungsten carbide (WC) and 40 wt % NiCrBSi was
      successfully made on the alloy. The high content of the hard WC particles is
      intended to enhance the abrasion resistance of the titanium alloy. The goal was
      to create a uniform distribution of hard WC particles that is crack-free and
      nonporous to enhance the wear resistance of such alloy. This was achieved by
      changing the laser cladding parameters to reach the optimum conditions for
      favorable mechanical properties. The laser cladding samples were subjected to
      thorough microstructure examinations, microhardness and abrasion tests. Phase
      identification was obtained by X-ray diffraction (XRD). The obtained results
      revealed that the best clad layers were achieved at a specific heat input value
      of 59.5 J.mm-2. An increase by more than three folds in the microhardness values
      of the clad layers was achieved and the wear resistance was improved by values
      reaching 400 times.

PMID- 29036934
TI  - Identification of Genetic Interaction with Risk Factors Using a Time-To-Event
      Model.
AB  - BACKGROUND: Certain diseases can occur with and without a trigger. We use Venous
      Thromboembolism (VTE) as our example to identify genetic interaction with
      pregnancy in women with VTE during pre- or postpartum. Pregnancy is one of the
      major risk factors for VTE as it accounts for 10% of maternal deaths. METHODS: We
      performed a whole genome association analysis using the Cox Proportional Hazard
      (CoxPH) model adjusted for covariates to identify genetic variants associated
      with the time-to-event of VTE related to pre- or postpartum during the
      childbearing age of 18-45 years using a case-only design in a cohort of women
      with VTE. Women with a VTE event after 45 years of age were censored and
      contributed only follow-up time. RESULTS: We identified two intragenic single
      nucleotide polymorphisms (SNPs) at genome-wide significance in the PURB gene
      located on chromosome 7, and two additional intragenic SNPs, one in the LINGO2
      gene on chromosome 9 and one in RDXP2 on chromosome X. CONCLUSIONS: We showed
      that the time-to-event model is a useful approach for identifying potential
      hazard-modification of the genetic variants when the event of interest (VTE)
      occurs due to a risk factor (pre- or post-partum).

PMID- 29036936
TI  - Barriers and Facilitators for Health Behavior Change among Adults from Multi
      Problem Households: A Qualitative Study.
AB  - Multi-problem households are households with problems on more than one of the
      following core problem areas: socio-economic problems, psycho-social problems,
      and problems related to child care. The aim of this study was to examine barriers
      and facilitators for health behavior change among adults from multi-problem
      households, as well as to identify ideas for a health promotion program. A
      qualitative study involving 25 semi-structured interviews was conducted among
      Dutch adults who received intensive family home care for multi-problem
      households. Results were discussed with eight social workers in a focus group
      interview. Data were analyzed using the Framework Method. The results revealed
      that the main reason for not engaging in sports were the costs. Physical activity
      was facilitated by physically active (transport to) work and by dog ownership.
      Respondents who received a food bank package reported this as a barrier for
      healthy eating. Those with medical conditions such as diabetes indicated that
      this motivated them to eat healthily. Smokers and former smokers reported that
      stress was a major barrier for quitting smoking but that medical conditions could
      motivate them to quit smoking. A reported reason for not using alcohol was having
      difficult past experiences such as violence and abuse by alcoholics. Mentioned
      intervention ideas were: something social, an outdoor sports event, cooking
      classes, a walking group, and children's activities in nature. Free or cheap
      activities that include social interaction and reduce stress are in line with the
      identified barriers and facilitators. Besides these activities, it may be
      important to influence the target group's environment by educating social workers
      and ensuring healthier food bank packages.

PMID- 29036937
TI  - Behaviors Related to Mosquito-Borne Diseases among Different Ethnic Minority
      Groups along the China-Laos Border Areas.
AB  - Background: In China, mosquito-borne diseases are most common in the sub-tropical
      area of Yunnan province. The objective of this study was to examine behaviors
      related to mosquito-borne diseases in different ethnic minority groups and
      different socioeconomic groups of people living in this region. Methods: A
      stratified two-stage cluster sampling technique with probability proportional to
      size was used in Mengla County, Xishuangbanna Prefecture, Yunnan. Twelve villages
      were used to recruit adult (>=18 years old) and eight schools were used for
      children (<18 years old). A questionnaire on behaviors and environment variables
      related to mosquito-borne diseases was devised. Results: Multiple correspondence
      analysis (MCA) grouped 20 behaviors into three domains, namely, environmental
      condition, bed net use behaviors, and repellent use behaviors, respectively. The
      Han ethnicity had the lowest odds of rearing pigs, their odds being significantly
      lower than those of Yi and Yao. For bed net use, Dai and other ethnic minority
      groups were less likely to use bed nets compared to Yi and Yao. The odds of
      repellent use in the Han ethnicity was lower than in Yi, but higher than in Dai.
      The Dai group was the most likely ethnicity to use repellents. Farmers were at a
      higher risk for pig rearing and not using repellents. Education of less than
      primary school held the lowest odds of pig rearing. Those with low income were at
      a higher risk for not using bed nets and repellent except in pig rearing. Those
      with a small family size were at a lower risk for pig rearing. Conclusion:
      Different ethnic and socioeconomic groups in the study areas require different
      specific emphases for the prevention of mosquito-borne diseases.

PMID- 29036939
TI  - Female Genital Mutilation Reconstruction: A Preliminary Report.
AB  - Background: Female genital mutilation (FGM) is internationally recognized as a
      violation of human rights. Though rarely discussed, FGM is prevalent, affecting
      hundreds of millions of females worldwide. Objectives: We believe that is
      important for plastic surgeons to be informed and prepared to address the
      surgical and emotional needs of these women. We present our experience on
      treatment of women subjected to FGM. Methods: Three consecutive patients were
      treated by our clitoral restoration procedure. The procedure involves conscious
      sedation and involves wide release of scar tissue around the labia majora and
      clitoris. Labial flaps are elevated and secured down to the periosteum and the
      clitoris is allowed to remucosalize. Results: Three females with grade II
      mutilation were treated. The average age was 32.3-years-old and the average
      follow up was 305 days. All patients self-reported improved sexual function and
      decreased embarrassment with their partners. And all recommended the treatment to
      other women subjected to FGM. Conclusions: FGM is a violation of the basic rights
      of women and children. Plastic surgeons can help these women restore their
      physical and psychological sense of well-being by providing effective
      reconstructive options. Our goal is to raise awareness of this problem and
      describe a simple yet effective treatment for women that have been subject to
      FGM. Level of Evidence: 5.

PMID- 29036940
TI  - Oculonasal Synkinesis: Video Report and Surgical Solution of a Rare Phenomenon.
AB  - Background: Synkinesis represents involuntary muscular movements that occur in
      association with voluntary contraction of other muscle groups. Oculonasal
      synkinesis is a rare phenomenon. Objectives: In a series of videos, the authors
      present clinical findings and surgical correction of oculonasal synkinesis.
      Methods: Two women who underwent surgical procedures to correct oculonasal
      synkinesis were evaluated in a prospective study. One patient presented with
      bilateral synkinesis after 2 previous rhinoplasties. She underwent open
      rhinoplasty in our office. The other patient had unilateral synkinesis of the
      left side and received endonasal rhinoplasty. Results: The patients' mean age was
      27.5 years, and follow-up was conducted for 6 months. Both patients experienced
      complete, stable resolution of synkinesis after surgical correction. No
      complications were recorded. Conclusions: Patients with oculonasal synkinesis may
      not notice it preoperatively and may regard these muscle movements as an
      unfavorable result of rhinoplasty. Therefore, careful preoperative evaluation is
      crucial.

PMID- 29036941
TI  - Breast Implant-Associated Anaplastic Large-Cell Lymphoma in a Transgender Woman.
AB  - : Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare
      but serious complication in patients with breast implants, Patients are at risk
      of BIA-ALCL whether they receive breast implants for cosmetic reasons or for
      reconstructive purposes after surgery for breast cancer or prophylactic
      mastectomy. During the past decade, an increased number of reports have addressed
      BIA-ALCL. Herein, we describe BIA-ALCL in a transgender woman. The patient
      received breast implants as part of her gender transition and was diagnosed with
      BIA-ALCL 20 years later. The patient underwent several revisional operations in
      the 20 years after her primary breast surgery to treat unexplained pain with low
      grade fever, severe capsular contracture (Baker grade III-IV), and several
      instances of implant rupture. In July 2016, the patient presented to our office
      with "late-onset" periprosthetic seroma 5 years after her last revisional breast
      surgery. She was diagnosed with BIA-ALCL without capsular invasion based on
      results of cytologic analysis of the periprosthetic seroma and histologic
      evaluation of the periprosthetic capsule. This diagnosis was verified further by
      results of immunohistochemical testing, which indicated expression of CD30 and T
      cell markers in the periprosthetic seroma only. Our intentions with this case
      report are to demonstrate that all patients who undergo breast implantation,
      including transgender women, are at risk of BIA-ALCL and to highlight the
      importance of cytomorphologic and immunohistochemical screening of seroma fluid
      in patients with late-onset periprosthetic seroma. LEVEL OF EVIDENCE: 5.

PMID- 29036942
TI  - Commentary on: Bilateral Breast Reduction Without Opioid Analgesics: A
      Comparative Study.

PMID- 29036943
TI  - Response to "Influences of Electrostatic or Triboelectric Charges and Breast
      Implant Symptomatic Contamination".

PMID- 29036938
TI  - Reactive Oxygen Species and NOX Enzymes Are Emerging as Key Players in Cutaneous
      Wound Repair.
AB  - Our understanding of the role of oxygen in cell physiology has evolved from its
      long-recognized importance as an essential factor in oxidative metabolism to its
      recognition as an important player in cell signaling. With regard to the latter,
      oxygen is needed for the generation of reactive oxygen species (ROS), which
      regulate a number of different cellular functions including differentiation,
      proliferation, apoptosis, migration, and contraction. Data specifically
      concerning the role of ROS-dependent signaling in cutaneous wound repair are very
      limited, especially regarding wound contraction. In this review we provide an
      overview of the current literature on the role of molecular and reactive oxygen
      in the physiology of wound repair as well as in the pathophysiology and therapy
      of chronic wounds, especially under ischemic and hyperglycemic conditions.

PMID- 29036944
TI  - Influences of Electrostatic or Triboelectric Charges and Breast Implant
      Symptomatic Contamination.

PMID- 29036945
TI  - What's Your Micromort? A Patient-Oriented Analysis of Breast Implant-Associated
      Anaplastic Large Cell Lymphoma (BIA-ALCL).
AB  - Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) continues to
      be a rare and elusive malignancy. Because BIA-ALCL does not behave like
      traditional lymphomas, additional research needs to be conducted to further
      delineate the lymphoproliferative nature of BIA-ALCL. An estimated 35 million
      women worldwide have breast implants and the total reported deaths from BIA-ALCL
      is 12 to date. The term micromort was introduced in 1979 by Ronald Howard as a
      person's risk of dying as 1 in a million. Drinking 0.5 L of wine or walking 17
      miles all increase your risk of death by 1 micromort. Risk of death from BIA-ALCL
      is 0.4 micromorts for a woman having bilateral breast implants. This information
      is important for counseling new patients and those presenting with delayed onset
      seromas.

PMID- 29036946
TI  - Commentary on: Breast Implant-Associated Anaplastic Large-Cell Lymphoma in a
      Transgender Woman.

PMID- 29036947
TI  - Commentary on: Oculonasal Synkinesis: Video Report and Surgical Solution of a
      Rare Phenomenon.

PMID- 29036949
TI  - [Paying more attentions to diagnosis and treatment of complex brucellosis].

PMID- 29036948
TI  - Commentary on: Transcutaneous Brow Shaping: A Straightforward and Precise Method
      to Lift and Shape the Eyebrows.

PMID- 29036950
TI  - [To attach great importance to the diagnosis and treatment of psychosomatic
      disorders in internal medicine].

PMID- 29036951
TI  - [The clinical and pathological features of patients with infective endocarditis
      diagnosed at autopsy].
AB  - Objective: To study the characteristics and misdiagnosis of infective
      endocarditis (IE). Methods: Clinical and pathological data of 15 IE patients
      diagnosed by autopsy were collected, compared with the cohort of 29 regular IE
      cases. Results: In the autopsy patients, IE in the left heart was predominat
      (14/15, 93.3%). Arterial embolism was the most common comorbidity (10/15, 66.7%),
      followed by pneumonia, malignancies, pyelonephritis (9/15, 60.0%; 7/15, 46.7%;
      6/15, 40.0% respectively). The age was elder [(64.0+/-21.2)years vs(50.8+/
      18.3)years, t=-2.15, P=0.037] in autopsy patients than in control group. More
      patients of missed diagnosis were combined with malignancies or deep vein
      catheterization [7/15(46.7%)vs 1/29(3.4%); 5/15(33.3%)vs 0/29(0)respectively].
      Fever and cardiac murmur were rare in misdiagnosed cases[11/15(73.7%)vs
      28/29(96.9%), 0/15(0)vs 15/29(51.7%) respectively]. Echocardiography and blood
      culture were performed in only 33.3%(5/15) and 26.7%(4/15) cases of missed
      diagnosis with low positive rates compared with regular IE patients [0/15(0) vs
      27/29 (93.1%); 1/15(6.7%) vs 15/29(55.6%)]. Conclusions: Infective endocarditis
      should be suspected in patients with the risk factors of IE even without fever or
      cardiac murmur. Echocardiography and blood culture should be done as screening
      tests of IE.

PMID- 29036952
TI  - [A clinical analysis of 20 patients with neurobrucellosis].
AB  - Objective: To investigate the epidemiological and clinical features of 20
      patients with neurobrucellosis (NB) . Methods: The epidemiological, clinical,
      laboratory and treatment data of patients diagnosed with NB from 2010 to 2016 in
      Peking Union Medical College Hospital were retrospectively analyzed. Results:
      Twelve (60%) patients reported the history of contact with infected animals and
      intake of raw milk product. The common manifestations included headache (85%,
      17/20), fatigue (85%, 17/20), fever (80%, 16/20), weight loss (70%, 15/20), the
      signs included pathological reflection (70%, 15/20), decreased muscle
      strength(45%, 9/20). The mean time to diagnosis was 7.9 months. All patients were
      diagnosed by positive serum antibody against Brucella. Body fluid culture
      revealed positive blood Brucella in 5 (31.2%, 5/16) patients and positive
      cerebrospinal fluid in 3 (16.7%, 3/18) patients. The medication consisted of
      rifampicin and minocycline based regimens or combined with ceftriaxone,
      fluroquinolone, streptomycin or trimethoprim-sulfamethoxazole (TMP-SMX). Ninety
      percent(18/20) patients obtained clinical improvement, whereas mild sequelae were
      observed in 5 patients. Conclusions: Clinical features of NB are heterogeneous.
      Carefully seek for epidemiological clues and early tests for Brucella may lead to
      well outcome. Combination therapy with two or more active antimicrobial agents is
      suggested.

PMID- 29036953
TI  - [A clinical analysis of six patients with Brucella endocarditis and literature
      review].
AB  - Objective: To analyze the epidemiology and clinical characteristics of patients
      with Brucella endocarditis in order to improve the understanding and treatment of
      Brucella endocarditis. Methods: The clinical data including demographic
      characteristics, clinical features, laboratory data, echocardiography, treatment
      and clinical outcome of 6 patients with Brucella endocarditis were collected and
      analyzed. Results: In our database consisting of 211 brucellosis patients with
      positive blood culture, 6 patients (2.8%) with Brucella endocarditis were
      selected from May 2007 to December 2016 in Peking Union Medical College
      Hospital.The age range was 25-55 years, among whom 5 patients were men.The
      majority were farmers and all patients reported the history of closely contact
      with livestock.All of them had fever and 3 of them had arthralgia.Four patients
      had aortic involvement (4/6) and 2 of them presented with symptoms of left
      ventricular failure at admission.Blood culture of Brucella and serum
      agglutination test of Brucella were positive in all of them.Combined antibiotics
      treatments were given to all patients.Valve replacement surgery was performed in
      four patients, among them, three patients well recovered, one lost. Among all the
      patients, four were followed up continually and other two were lost.
      Conclusions:Brucella endocarditis has a predominance of aortic involvement and is
      prone to left ventricular failure.Early antibiotic treatment combined with valve
      replacement surgery is effective to improve the prognosis.

PMID- 29036954
TI  - [Relationship between highly sensitive cardiac troponin T and sepsis and outcome
      in critically ill patients].
AB  - Objective: To investigate the prognostic value of highly sensitive cardiac
      Troponin T (hs-cTn T) for sepsis in critically ill patients. Methods: Patients
      estimated to stay in the ICU of Fuxing Hospital for more than 24h were enrolled
      at from March 2014 to December 2014. Serum hs-cTn T was tested within two hours.
      Univariate and multivariate linear regression analyses were used to determine the
      association of variables with the hs-cTn T. Multivariable logistic regression
      analysis was used to evaluate the risk factors of 28-day mortality. Results: A
      total of 125 patients were finally enrolled including 68 patients with sepsis and
      57 without. The levels of hs-cTn T in sepsis and non-sepsis groups were
      significantly different[52.0(32.5, 87.5) ng/L vs 14.0(6.5, 29.0) ng/L
      respectively, P<0.001]. In sepsis group, hs-cTn T among common sepsis, severe
      sepsis and septic shock were similar. Hs-cTn T was significantly higher in non
      survivors than survivors [27(13, 52)ng/L vs 44.5(28.8, 83.5)ng/L, P<0.001]. Age,
      sepsis, serum creatinine were independent risk factors affecting hs-cTn T by
      multivariate linear regression analyses. But hs-cTn T was not a risk factor for
      death. Conclusion: Patients with sepsis had higher serum hs-cTn T than those
      without sepsis. but it was not found to be associated with the severity of
      sepsis.

PMID- 29036955
TI  - [Comparision of risk factors and pathogens in patients with early- and late-onset
      ventilator-associated pneumonia in intensive care unit].
AB  - Objective: To compare risk factors and bacterial etiology in patients with early
      onset versus late-onset ventilator-associated pneumonia (VAP) in intensive care
      unit (ICU). Methods: This prospective cohort study enrolled mechanically
      ventilated patients hospitalized for more than 48 hours in the first affiliated
      hospital, China Medical University from Jan 2012 to Jun 2016. Subjects were
      classified by ventilator status: early-onset VAP (< 5 d ventilation, E-VAP) or
      late-onset VAP (>= 5 d ventilation, L-VAP). Potential risk factors and pathogen
      were evaluated. Results: A total of 4 179 patients in adult ICU were screened, 3
      989 (95.5%) of whom were mechanically ventilated, 962 patients with mechanical
      ventilation time >= 48 h. VAP developed in 142 patients. E-VAP and L-VAP had
      different potential risk factors based on statistical analysis.Independent risk
      factors for E-VAP included male (OR=1.825, 95%CI 1.006-3.310), chronic
      obstructive pulmonary disease (COPD; OR=3.746, 95%CI 1.795-7.818), emergency
      intubation (OR=1.932, 95%CI 1.139-3.276), aspiration (OR=3.324, 95%CI 1.359
      8.130). Whereas independent risk factors for L-VAP were coma (OR=2.335, 95%CI
      1.300-4.194), renal dysfunction (OR=0.524, 95%CI 0.290-0.947), emergency
      intubation (OR=2.184, 95%CI 1.334-3.574). Mortality in E-VAP and L-VAP group were
      both higher than the non-VAP group[30.2%(19/63)vs 19.8%(162/820), P=0.044;
      29.1%(23/79) vs 19.8%(162/820), P=0.046]. The pathogens isolated from early-onset
      versus late-onset VAP were not significantly different between groups, which the
      most common ones were acinetobacter baumannii, pseudomonas aeruginosa and
      klebsiella pneumoniae. Conclusion: E-VAP and L-VAP have different risk factors,
      however related pathogens are similar. Different specific preventive strategies
      are suggested based on different onset of VAP.

PMID- 29036956
TI  - [The diagnostic value of neuron-specific enolase, central nervous system specific
      protein and interleukin-6 in sepsis-associated encephalopathy].
AB  - Objective: To investigate the diagnostic value of neuron-specific enolase(NSE),
      central nervous system specific protein(S100beta), interleukin-6(IL-6) in sepsis
      associated encephalopathy(SAE). Methods: Clinical data of patients admitted to
      ICU and diagnosed with sepsis were collected from January 2015 to June 2016 in
      Xiangya Hospital, Central South University. SAE was defined as cerebral
      dysfunction in the presence of sepsis that also fulfilled the exclusion criteria.
      The acute physiology and chronic health score (APACHE II), sequential organ
      failure assessment (SOFA), NSE, S100beta, IL-6, ICU stay time and 28-day
      mortality were compared between the two groups. NSE, S100beta and IL-6 were
      measured on the 1st and 3rd day in ICU to determine the optimal cut-off value of
      SAE. Results: Among 59 enrolled patients, 36 were assigned to SAE group while 23
      were non-SAE group. The SAE group had a significantly higher APACHE II and SOFA
      scores, as well as the length of ICU stay (P<0.01). The levels of NSE, S100beta
      and IL-6 in the two groups both increased on the 1st day, and decreased on the
      3rd day. The level of NSE on the 1st day[19.28(13.00, 30.52) MUg/L vs 16.61(7.58,
      22.01 MUg/L)] and the 3rd day[16.03(9.40, 21.29) MUg/L vs 11.39(8.49, 15.00)
      MUg/L, P=0.029], IL-6 on the 1st day[676.25(81.34, 5 000.00) mg/L vs
      [209.10(42.27, 648.20) mg/L, P=0.005] and the 3rd day[157.10(72.85, 687.63) mg/L
      vs 55.92(31.62, 177.00) mg/L, P=0.026] of SAE group was significantly higher than
      those of non-SAE group. However S100beta between groups on the 1st day
      [0.33(0.15, 0.54) MUg/L vs 0.23(0.16, 0.53) MUg/L] and the 3rd day[0.19(0.10,
      0.29) MUg/L vs 0.10(0.05, 0.17) MUg/L] was neither significant (P>0.05). The
      diagnostic values for SAE of NSE, S100beta and IL-6 were 14.36 MUg/L, 0.14 MUg/L
      and 91.305 mg/L with sensitivity 61.1%, 61.1%, 72.2% and specificity 73.9%,
      69.6%, 69.6%, respectively. The diagnostic AUC of NSE and IL-6 combination was
      0.774, 95%CI 0.651-0.896. Conclusion: All sepsis patients have different degrees
      of brain injury. NSE combined with IL-6 on the 3rd day in ICU demonstrates the
      diagnostic significance of SAE.

PMID- 29036957
TI  - [A meta-analysis of randomized controlled trials of bismuth-containing quadruple
      therapy combined with probiotic supplement for eradication of Helicobacter
      pylori].
AB  - Objective: The bismuth containing quadruple therapy (BCQT) acts as first-line
      therapy in China. Probiotics supplement also shows Helicobacter pylori
      eradication effects. Adding probiotics along with BCQT may improve eradication
      rate of Helicobacter pylori. Methods: Electronic databases including Medline,
      Embase, Wanfang Database, etc. were searched by the established searching
      strategy. After that, a funnel plot was adopted to evaluate publication bias. The
      meta-analysis was supplemented in fixed effect model for low heterogeneity and
      randomized effect model for high heterogeneity conversely. Results: A total of 16
      RCTs with 2 466 subjects finally met the inclusion criteria. There was no
      significant heterogeneity among the trials. Compared with control group (BCQT
      only), the probiotic group (combined supplement of probiotics and BCQT) underwent
      higher eradication rate[90.76%(1 130/1 245) vs 80.43%(982/1 221)]with statistical
      significance (P=0.000). The probiotics might improve the eradication rate in
      patients not receiving previous eradication therapy [89.00%(445/500) vs
      84.73%(416/491), P=0.04]. Probiotics might also improve the eradication
      rate[91.06%(326/358) vs 73.83%(268/363)]in patients relapsed from triple therapy
      (P=0.000). The patients who underwent the combination of BCQT and single
      Lactobacillus genus showed higher eradiation rate than those with two or more
      genera. Moreover, fewer adverse reactions were reported in probiotics group than
      that in control group[13.59%(104/765) vs 28.90%(213/737), P=0.000]. Conclusions:
      The combination of BCQT and probiotics may improve the eradication rate of
      Helicobacter pylori especially in patients receiving front-line eradication
      regimen or failed from triple therapy. Probiotics may reduce the adverse
      reactions when combined with other eradication agents.

PMID- 29036958
TI  - [A clinical and hereditary analysis of novel complex heterozygous KCNJ1 mutation
      in a Bartter syndrome type II patient].
AB  - Bartter syndrome (BS) is a hereditary condition transmitted as an autosomal
      recessive (Bartter type 1 to 4) or dominant trait (Bartter type 5). The disease
      associates hypokalemic alkalosis with varying degrees of hypercalciuria. Here we
      presented a case (BS type II) of a 17 years old female presented with
      polyhydramnios, polyuria, nephrocalcinosis and hypokalemia, which was alleviated
      after treatment with celecoxib and vitamin D(3). DNA sequencing identified
      compound heterozygous KCNJ1 gene mutations, c. 931C >T (p.R311W) and c. 445
      446insCCTGAACAC (p.V149Afs, 150X), with the latter a novel mutation. Her father
      and mother were heterozygous carriers of c. 931C >T (p.R311W) and c. 445
      446insCCTGAACAC (p.V149Afs, 150X), respectively. In conclusion, this case of BS
      type II is caused by a novel compound heterozygous KCNJ1 mutation. Further
      studies are needed to verify the effect of celecoxib in BS patients.

PMID- 29036959
TI  - [The study of liver macrophages polarization in patients with autoimmune
      hepatitis].
AB  - To explore the functional phenotype of liver macrophages in patients with
      autoimmune hepatitis (AIH). Compared with patients with nonalcoholic fatty liver
      disease (NAFLD) and chronic hepatitis B (CHB), the absolute CD(68)(+) cell count
      in patients with AIH was significantly higher (all P<0.05). It was positively
      correlated with ALT and IgG levels (the correlation coefficients 0.600 and 0.700,
      P=0.285 and 0.188 respectively). Additionally, compared with patients with NAFLD,
      the absolute iNOS positive cell count in patients with AIH and CHB were
      significantly higher (all P<0.05). The expression of TNFalpha, iNOS and IL-1beta
      in patients with AIH and CHB were significantly higher than in patients with
      NAFLD (all P<0.05). Interestingly, compared with patients with AIH and CHB, the
      absolute CD(206)(+) cell count in patients with NAFLD were significantly higher
      (all P<0.05). CD(206) expression in patients with NAFLD was higher than patients
      with AIH and CHB, but with no statistical significance. M1 type macrophages over
      expressed and played a major role in the inflammatory reaction and liver injury
      in patients with AIH.

PMID- 29036960
TI  - [Two cases report of primary aldosteronism with positive cardiac troponin].

PMID- 29036961
TI  - [Ovarian carcinoma-associated hyperamylasemia masquerading as acute pancreatitis:
      a case report].

PMID- 29036962
TI  - [Cladribine in the treatment of TET2(+) refractory acute myeloid leukemia: a case
      report].

PMID- 29036963
TI  - [Common questions about clinical management of complicated urinary tract
      infections].

PMID- 29036965
TI  - [The mechanism of drug resistance in Acinetobacter baumannii and updates of
      development in novel antibiotics].

PMID- 29036964
TI  - [Initial therapy of invasive candidiasis: echinocandin or fluconazole?]

PMID- 29036966
TI  - [The genetic characteristics of frontotemporal dementia and its correlation to
      amyotrophic lateral sclerosis].

PMID- 29036967
TI  - [What's new in the 2016 American Thyroid Association guidelines for diagnosis and
      management of hyperthyroidism and other causes of thyrotoxicosis].
AB  - The 2016 American Thyroid Association guidelines for diagnosis and management of
      hyperthyroidism and other causes of thyrotoxicosis has been officially published
      in October of 2016, five years after the publication of the previous version.
      Revised contents in the new guideline are summarized in this review.

PMID- 29036968
TI  - [The 458th case: fever, cytopenia, abdominal pain, and multiple intestinal
      ulcerations with perforation].
AB  - Trisomy 8 in myelodysplastic syndrome (MDS) plays an important role in concurrent
      intestinal Behcet's disease (BD) pathogenesis. Here, we reported a case of
      intestinal BD combined with MDS involving trisomy 8. A 48-year-old woman who has
      had a 20-year history of recurrent oral ulcer, perineal ulcer and iris, was
      diagnosed as MDS with trisomy 8 four years ago. She developed high fever and
      acute abdominal pain. Multiple ulcerative perforations in ileum and colon were
      found by endoscopy, meeting the criteria for intestinal BD. The patient was
      successfully treated with immunomodulatory drugs.

PMID- 29036969
TI  - [Risk factors, prevalence, diagnosis and treatment of hypertrophic cardiomyopathy
      patients complicating with atrial fibrillation].

PMID- 29036970
TI  - [Update on the diagnosis and management of cardiac sarcoidosis].

PMID- 29036971
TI  - [Chinese expert consensus statement on clinical diagnosis and treatment of
      fulminant myocarditis in adults].

PMID- 29036972
TI  - [Analysis of influencing factors of heart rate deceleration capacity in patients
      with dilated cardiomyopathy].
AB  - Objective: To investigate the determinants affecting the heart rate deceleration
      capacity (DC) in patients with dilated cardiomyopathy (DCM). Methods: One hundred
      patients with DCM (DCM group) and 202 healthy subjects (control group) were
      respectively enrolled. Echocardiography and 24 hours electrocardiogram were
      performed in all subjects. DC value was compared between the two groups. Multiple
      regression analysis was made to evaluate the related determinants of DC ((age,
      sex, echocardiographic parameters including the left atrial diameter (LAD) and
      left ventricular ejection fraction (LVEF)). Results: (1) DC value was
      significantly lower in DCM group than in control group( (4.40+/-2.03) ms vs.
      (7.30+/-1.81) ms, P<0.01), prevalence of DC value<=4.5 ms was significantly
      higher in DCM group than in control group (62% vs. 6%, P<0.01). (2) DC value in
      the DCM group decreased in proportion to increasing LAD dimension, DC value was
      (5.60+/-2.04) ms, (4.50+/-2.07) ms and (3.60+/-1.62) ms (P<0.05) in DCM patients
      with LAD<=40 mm, 40 mm<LAD<=50 mm and LAD>50 mm, respectively. (3) DC value in
      the DCM group was negatively related to the LAD (r=-0.366, P<0.01), positively
      related to the LVEF (r= 0.241, P<0.01), but not related with age and sex.
      Multiple factors regression analysis showed that increased LAD was related to the
      reduced DC values independtly. Conclusion: DC value of the patients in the DCM
      group is decreased, which indicate the decrease of the vagus nerve tension, and
      increased LAD is related to the reduced DC value independtly in DCM patients.

PMID- 29036973
TI  - [Predictive value of cardiac magnetic resonance-derived parameters on the
      improvement of left ventricular function in patients with acute viral
      myocarditis].
AB  - Objective: To evaluate the predictive value of cardiac magnetic resonance (CMR)
      derived parameters on the improvement of left ventricular function in patients
      with acute viral myocarditis. Methods: Forty patients, who referred for acute
      viral myocarditis in our hospital from September 2011 to September 2015, were
      prospectively enrolled in this study.All patients were examined by CMR during
      hospitalization for acute viral myocarditis (baseline) and after 12 months.The
      CMR sequences include: two dimension steady state free precession, 2D SSFP;
      triple inversion recovery, triple IR; early gadolinium enhancement; phase
      sensitive inversion recovery turbo field echo, PSIR TFE. Results: Thirty out of
      40 patients with susceptive acute viral myocarditis met the CMR criteria of acute
      viral myocarditis (Lake Louise Criteria) (LL+ ) and the other 10 patients did not
      meet the diagnostic criteria (LL-). Left ventricular ejection fraction (LVEF)
      values were significantly lower in LL+ group than in LL- group at baseline and at
      12 months after discharge (P<0.01 or 0.05, respectively). The baseline left
      ventricular end-systolic volume index (LVESVI) was significantly higher in LL+
      group than in LL- group (P<0.05) and was similar between the groups at 12 months
      follow up.Left ventricular end-diastolic volume index (LVEDVI )was similar
      between the two groups at baseline and at 12 months follow up.LVEF was
      significantly higher during 12 months follow up compared to baseline in LL+ group
      and remained unchanged in LL- group during the two time points.LVESVI and LVEDVI
      remained unchanged at baseline and during 12 months follow up both in LL+ and LL-
      groups (P>0.05). Results showed that LL+ , edema ratio (ER) positive and global
      relative enhancement (gRE) positive were associated with significant increase of
      LVEF at 12 months follow up.However, LL-, ER negative, gRE negative, late
      gadolinium enhancement(LGE) negative and LGE positive linked with unchanged LVEF
      at 12 months follow up (P>0.05). Patients were further divided into LVEF increase
      (DeltaLVEF>=5%) group and non LVEF increase group (DeltaLVEF<5%), the results of
      Chi-square test showed that LL+ and ER positive were related to the improvement
      of LVEF (P<0.05), while gRE and LGE were not associated with improvement of
      cardiac function (P>0.05). Multiple linear regression analysis, using ER, gRE and
      LGE as independent variables and LVEF as dependent variables, showed that the
      presence of myocardial edema was the strongest independent predictor of an
      increase in LVEF at follow up (full model: non-standardized coefficient 0.445,
      P=0.043; reduced model: non-standardized coefficient 0.442, P=0.12). Conclusion:
      Cardiac magnetic resonance imaging monitoring is valuable to observe the cardiac
      function and morphology changes in patients with acute viral myocarditis, and
      myocardial edema imaging is the most powerful parameter to predict the
      improvement of LVEF in this patient cohort.

PMID- 29036974
TI  - [The impact of hydrogen sulfide on the heme oxygenase-1/carbon monoxide system in
      Coxsackie virus B3-induced myocarditis in mice].
AB  - Objective: To explore the impact of hydrogen sulfide (H(2)S) on the heme
      oxygenase-1/carbon monoxide pathway in Coxsackie virus B3 (CVB3)-induced murine
      myocarditis (VMC) model. Method: A total of 70 inbred male Balb/c mouse (4-6
      weeks old) were randomized into the following four groups: Normal, VMC, PAG and
      NaHS (n=10 for Normal, n=20 for VMC, PAG and NaHS groups). Mice in Normal group
      were non-infected mice treated with intraperitoneal injection of sterile
      phosphate-buffered saline daily for 10 days.Mice in VMC group received
      intraperitoneal CVB3 injection (0.1 ml 10(-5.69)TCID(50)m.ml(-1).d(-1) and PBS
      for 10 days), and mice in PAG group received additional intraperitoneal DL
      proparglygylcine injection (40 mg.kg(-1).d(-1) for 10 days), mice in NaHS group
      received additional intraperitoneal NaHS injection (50 MUmol.kg(-1).d(-1) for 10
      days). All mice were sacrificed on day 10th, and body weight and heart weight,
      the ratio of heart weight to body weight were compared among groups.Pathological
      changes of heart tissues were observed microscopically by HE and the
      histopathologic scores were valued.The content of COHb was tested after the
      gathering of blood specimens while reverse transcription-polymerase chain
      reaction was used to detect myocardial HO-1 mRNA expression. Results: (1)
      Pathological findings in myocardium: hearts sections in Normal group were normal
      and no inflammatory cells and necrosis were found.A notable cellular
      infiltration, interstitial edema, vascular hyperemia and necrosis were observed
      in heart section of VMC, PAG and NaHS group.Extensive inflammations and larger
      area of myocardial cells necrosis were evidenced in PAG group and above changes
      were significantly reduced in NaHS group.(2) Comparison of the ratio of heart
      weight to body weight and histological scores of myocardium: the ratio was
      significantly higher in the VMC, PAG, NaHS groups than in Normal group (P<0.05),
      which was higher in PAG group and lower in NaHS group as compared with VMC group
      (both P<0.05). The histopathologic scores of all CVB3 innoculation groups were
      higher than in the Normal group, which was higher in PAG group and lower in NaHS
      group as compared to VMC group (both P<0.05). (3) The content of blood COHb in
      VMC, PAG or NaHS group was significantly higher than that in Normal group
      (P<0.05), which was significantly lower in PAG group, and higher in NaHS group as
      compared to VMC group (both P<0.05). (4) The mRNA expression of myocardial HO-1
      detected by RT-PCR: weak expression was observed in Normal group, which was
      significantly upregulated in VMC, PAG and NaHS groups (P<0.05), which was
      downregulated in PAG group and upregulated in NaHS group as compared to VMC group
      (both P<0.05). (5) Correlation analysis: blood COHb concentration was positively
      correlated with myocardial HO-1 mRNA expression(r=0.927, P=0.000), negatively
      correlated with histopathologic scores(r=-0.753, P=0.000)and the histopathologic
      scores were negatively correlated with the myocardial HO-1 mRNA expression (r=
      0.754, P=0.000). Conclusions: H(2)S could play a protective role in murine CVB3
      myocarditis model through inducing HO-1 expression and upregulating HO-1/CO
      pathway.

PMID- 29036975
TI  - [Predictive value of serial platelet function testing on outcome in patients
      undergoing complex percutaneous coronary intervention].
AB  - Objective: To observe the predictive value of serial platelet function testing
      (PFT) on outcome in patients undergoing complex percutaneous coronary
      intervention (PCI). Methods: Six hundred and two consecutive patients undergoing
      complex PCI in Anzhen hospital were enrolled during October 2011 to June
      2012.Adenosine diphosphate(ADP)-induced platelet aggregation was measured by
      light transmission aggregometry on the first, sixth and twelfth month after PCI
      and the mean value was calculated.The cut-off value of high on-treatment platelet
      reactivity (HTPR) was defined as 40%.The primary endpoint was major adverse
      cardiovascular and cerebral event (MACCE). Clinical outcomes were analyzed by the
      Kaplan-Meier method and differences were compared using the log-rank
      test.Multivariate analyses by Cox proportion hazards regression were applied to
      identify variables independently associated with the adverse outcomes. Results:
      Five hundred and eighty-five patients (HTPR, n=285; non-HTPR, n=280) finished the
      follow-up ((28.47+/-7.45) months). A total of 33 cases of MACCE were observed
      during the follow-up, among which 29 cases(8.42%) were in HTPR group and 9 cases
      (3.21%) in the non-HTPR group.Kaplan-Meier analysis suggested that HTPR was
      associated with an increased incidence of MACCE (log-rank test, P=0.01). The Cox
      multivariate analysis indicated that HTPR was an independent risk factor of MACCE
      (HR=2.69, 95%CI 1.23-5.85, P=0.01) in patients undergoing complex PCI.Incidence
      of MACCE was similar between HTRP patients receiving standard dual antiplatelet
      therapy (DAPT) or prolonged DAPT (>12 months). Conclusion: Serial PFT could
      predict the long-term prognosis of patients underwent complex PCI.

PMID- 29036977
TI  - [Safety and feasibility of sheathless transfemoral aortic valve implantation].
AB  - Objective: To investigate the safety and feasibility of sheathless transfemoral
      aortic valve replacement (TAVR). Methods: In this prospective study, we enrolled
      23 patients with severe aortic stenosis (AS) who were inoperable or at high-risk
      for surgical aortic valve replacement operation in Fuwai hospital From September
      2012 to June 2015. Multislice spiral CT and angiography of femoral artery showed
      that all patients had minimal femoral artery diameters (<6.5 mm) and severe
      calcification which was not suitable for transfemoral TAVR through sheath. We
      attempted to apply the sheathless transfemoral TAVR using Venus-A prosthesis
      without sheath insertion, and procedure related complication during the procedure
      and hospital stay were observed. Results: The 6 mm*30 mm balloon was used for
      femoral artery predilation in 1 patient with iliofemoral artery stenosis before
      delivery system was transported. In the other 22 patients, the delivery system
      was transported directly. A total of 21 patients finished TAVR with transfemoral
      sheathless technique. In 2 patients, prosthesis was unable to fully expand after
      release due to severe valve calcification, and patients received urgent surgical
      aortic valve replacement. One patient had valve dislocation into the ascending
      aorta that was not related to the sheathless replacement technique, and delivery
      system and Venus-A valve were removed after femoral artery was opened surgically,
      and repeated sheathless TAVR implantation was performed and was successful.
      Moderate aortic regurgitation occurred in 2 patients immediately after procedure,
      and trace or mild aortic regurgitation was detected in rest of the patients. One
      patient had puncture site rupture and bleeding after procedure, and was
      successfully treated by balloon compression without blood transfusion. Complete
      atrioventricular block occurred in 3 patients within 24 hours after procedure and
      lasted after 48-72 hours, permanent pacemakers were implanted in these patients.
      Conclusion: The sheathless transfemoral technique in TAVR is safe and feasible in
      severe aortic stenosis patients with small access vessel diameter.

PMID- 29036976
TI  - [Comparison of perioperative serum thrombomodulin levels in patients underwent
      off-pump coronary artery bypass grafting with and without cardiogenic shock].
AB  - Objective: To observe the perioperative changes of serum thrombomodulin in
      patients with and without cardiogenic shock undergoing off-pump coronary artery
      bypass grafting surgery. Methods: A total of 66 patients with coronary artery
      disease who underwent off-pump coronary artery bypass grafting surgery between
      June and December 2015 in our hospital were included in this study.The patients
      were divided into non-cardiogenic shock group (n=51) and shock group (n=15)
      according to the absence or presence of cardiogenic shock.The clinical data of
      the two groups were analyzed.Arterial blood samples were collected immediately
      after anesthesia, and at 4, 8, 16, 24, 48 and 72 hours after surgery.The levels
      of serum thrombomodulin were tested with enzyme-linked immunosorbent assay.
      Results: (1)The prevalence of diabetes was significantly higher (64.7%(33/51) vs.
      20.0%(3/15), P<0.01), while prevalence of myocardial infarction was significantly
      lower (41.2%(21/51)vs. 100%(15/15), P<0.01) in non-cardiogenic shock group than
      in cardiogenic shock group.(2)The peak plasma creatinine level, troponin I level
      and creatine kinase MB level were significantly lower in the non-cardiogenic
      shock group than in the cardiogenic shock group ((88.5+/-36.7) MUmol/L vs.
      (122.6+/-71.1) MUmol/L, 1.3(0.2, 2.7) MUg/L vs. 16.4(5.8, 23.4) MUg/L and (18.8+/
      4.7) MUg/L vs.(49.3+/-15.9) MUg/L, respectively, all P<0.05). (3)Mechanical
      ventilation time was significantly longer (11.5 (9.0, 18.0) hours vs. 20.0 (8.5,
      82.5) hours, P=0.02), and frequency of intra-aortic balloon pump use (0 vs. 100%,
      P<0.01) was significantly higher in the cardiogenic shock group than in the non
      cardiogenic shock group.(4) Prevalence of atrial fibrillation (5.9%(3/51) vs.
      80.0%(12/15)) and myocardial infarction (19.6%(10/51)vs. 93.3%(14/15)) that
      occurred during and after surgery was significantly lower in the non-cardiogenic
      shock group than in the shock group(all P<0.01). (5)The serum thrombomodulin
      concentration was similar among various time point in the non-cardiogenic shock
      group: 3.30(2.68, 7.44), 4.09(2.95, 7.18), 4.35(2.68, 8.22), 3.50(2.95, 8.00),
      3.41(2.60, 5.97), 3.30(2.65, 5.42)and 3.94(2.82, 5.60) MUg/L, taken immediately
      after anesthesia, and at 4, 8, 16, 24, 48 and 72 hours after surgery
      respectively, and was 2.44(1.97, 2.67), 2.21(1.93, 2.83), 2.64(2.29, 2.67),
      2.84(2.26, 2.94), 3.35(2.43, 4.05), 2.76(2.73, 2.97) and 3.81(2.96, 5.96)MUg/L
      respectively, in the cardiac shock group (all P>0.05). The serum thrombomodulin
      levels at 4 and 8 hours after surgery were higher in the non-cardiogenic shock
      group than cardiogenic shock group(all P<0.05). Conclusion: Compared with the non
      cardiogenic shock group, the peak serum thrombomodulin level appears later and
      recovers slower in cardiogenic shock patients who underwent off-pump coronary
      artery bypass grafting surgery.

PMID- 29036978
TI  - [Clinical features and surgical treatment effect of patients with cardiac
      cavernous hemangioma].
AB  - Objective: To investigate the clinical features and surgical treatment effect of
      patients with cardiac cavernous hemangioma. Methods: Clinical data of 9 patients
      (5 male, aged from 4 to 53 years old) with cardiac cavernous hemangioma, who
      underwent surgical treatment from November 2002 to March 2015 and the diagnosis
      of cardiac cavernous hemangioma was confirmed by postoperative histological
      examination, were retrospectively analyzed. Effects of surgical treatment were
      analyzed. Results: Four patients were asymptomatic (heart murmur presented in 3
      patients during physical examination). Three patients presented with palpitation,
      chest distress, and short of breath. One patient presented with epigastric
      discomfort and another patient presented with intermittent fever for more than 10
      months. ST and T wave changes of electrocardiogram were found in 2 patients,
      cardiac mass was detected in the right heart chamber in 5 patients by
      echocardiography, and no cardiac mass was detected the rest 4 patients. Cardiac
      masses were resected en bloc, then the adjacent tissues were repaired in 7
      patients, and mass was partially resected due to the involvement with adjacent
      heart structure. No cardiac mass was found during operation in 1 case, impaired
      mitral valve structure was excised and postoperative pathologically confirmed as
      cardiac valve cavernous angioma on the excised mitral valve structure. No signs
      of recurrence or enlargement of cardiac cavernous hemangioma were found during
      the 11(10, 11)years follow up. Conclusions: There is no specific clinical feature
      for patients with cardiac cavernous hemangioma. It is difficult to detect the
      cardiac valve cavernous angioma by echocardiography before surgery.
      Individualized surgical treatment is associated with good clinical outcome in
      this patient cohort. However, the clinical features and surgical treatment effect
      of patients with cardiac cavernous hemangioma still need to investigate in large
      sample trial.

PMID- 29036979
TI  - [Role of ash2 (absent, small, or homeotic)-like and Jumonji domain-containing
      protein 3 on histone methylation of interferon-gamma gene and their associations
      with vascular damage of Kawasaki disease].
AB  - Objective: To investigate the impacts of ash2 (absent, small, or homeotic)-like
      (Ash2L) and Jumonji domain-containing protein 3 (Jmjd3) on histone methylation of
      interferon-gamma(IFN-gamma) gene and association with vascular damage of Kawasaki
      disease (KD) in acute phase. Methods: This study was performed among 36 children
      with KD in acute phase (KD group) and 28 age-matched health children (control
      group), who were treated or underwent physical examination in our hospital
      between February 2015 and June 2016. Patients were further divided into KD groups
      with or without coronary artery lesions (KD-CAL(+) , 16 cases; KD-CAL(-), 20
      cases). All KD patients were treated with intravenous immunoglobulin. The
      proportion of type 1 helper T(Th1) cells and protein levels of IFN-gamma, T-box
      expressed in T cells(T-bet), phosphorylated signal transducer and activator of
      transcription 1(pSTAT1) and phosphorylated signal transducer and activator of
      transcription 4(pSTAT4) were analyzed by flow cytometry.Chromatin
      immunoprecipitation was performed to determine histone methylation (histone H3
      tri-methyl K4(H3K4me3), histone H3 tri-methyl K27(H3K27me3)) and binding levels
      of Ash2L, Jmjd3 and Ezh2 associated with IFN-gamma in CD4(+) T cells.
      Quantitative real-time PCR was used to determine mRNA levels of IFN-gamma,
      interferon gamma receptor 1(IFN-gammaR1), interferon gamma receptor 2(IFN
      gammaR2), interleukin 12 receptor subunit beta 1(IL-12Rbeta1), interleukin 12
      receptor subunit beta 2(IL-12Rbeta2), interleukin 18 receptor subunit beta
      alpha(IL-18Ralpha), interleukin 18 receptor subunit beta beta(IL-18Rbeta), tumor
      necrosis factor receptor 1(TNFR1), toll-like receptor 4(TLR4), receptor
      interacting serine/threonine kinase 1(RIP-1) and myeloid differentiation primary
      response gene 88(MyD88) in CD4(+) T cells. Plasma concentrations of IFN-gamma,
      interleukin 12(IL-12), interleukin 18(IL-18) and tumor necrosis factor alpha(TNF
      alpha) were measured by enzyme-linked Immunosorbent assay. Results: (1)The
      proportion of Th1 and its protein level of IFN-gamma were significantly higher in
      KD group than those in control group and higher in KD-CAL(+) group than in KD
      CAL(-) group (all P<0.05), and lower after treatment than before treatment (all
      P<0.05). (2)Compared with control group, mRNA level of IFN-gamma and IFN-gamma
      associating H3K4me3 was increased, while level of IFN-gamma associating H3K27me3
      in CD4(+) T cells was reduced in KD group (all P<0.05), which resulted in a
      higher rate of H3K4me3/H3K27me3 (P<0.05) in KD group, which was positively
      correlated with IFN-gamma mRNA in KD group(r=0.55, P<0.05). Similar results were
      found between KD-CAL(+) group and KD-CAL(-) group (all P<0.05). Level of IFN
      gamma associating H3K27me3 was increased, and mRNA level of IFN-gamma and IFN
      gamma associating H3K4me3 was decreased after treatment than before treatment
      (all P<0.05). (3)Expression of T-bet protein and binding levels of Ash2L and
      Jmjd3 with IFN-gamma gene were significantly higher in KD group than those in
      control group(all P<0.05), higher in KD-CAL(+) group than those in KD-CAL(-)
      group (all P<0.05). These parameters were significantly lower after treatment
      than before treatment (all P<0.05). Binding level of Ezh2 with IFN-gamma gene was
      similar among various groups (all P>0.05). (4)In comparison with control or after
      treatment, surface receptors(IFN-gammaR1/2, IL-12Rbeta1/2, IL-18Ralpha/beta,
      TNFR1 and TLR4) and its downstream molecules(pSTAT1, pSTAT4, RIP(1) and MyD88) in
      CD4(+) T cells, and plasma concentrations of inflammatory cytokines(IFN-gamma, IL
      12, IL-18 and TNF-alpha) were found to be higher in KD group(all P<0.05). These
      parameters were also higher in KD-CAL(+) group than in KD-CAL(-) group (all
      P<0.05). Conclusion: Aberrant histone methylation of IFN-gamma associating
      H3K4me3 and H3K27me3 caused by over-binding of Ash2L and Jmjd3 might be involved
      in immune dysfunction and vascular damage in KD in the acute phase.

PMID- 29036981
TI  - [A case of Takotsubo syndrome].

PMID- 29036980
TI  - [CD137 induces vascular muscle cells phenotype transformation through activating
      nuclear factor of activated T-cells 1 signaling].
AB  - Objective: To investigate whether CD137 induces primary vascular muscle cells
      (VSMCs) phenotype transformation through activating nuclear factor of activated T
      cells 1(NFATc1) signaling. Methods: VSMCs were obtained from aorta of C57BL/6J
      mice (8 weeks, male) through tissue-piece inoculating. Cells were divided into
      control group, CD137 agonist group (treated with CD137L recombinant protein) and
      anti-CD137 group (treated with anti-CD137 antibody). In si-RNA transfection
      assay, cells were divided into si-control group and si-NFATc1 group which were
      transfected with control or si-NFATc1 sequence respectively. The levels of NFATc1
      and other phenotype related protein such as alpha-smooth muscle actin (alpha
      SMA), smooth muscle myosin heavy chain (SM-MHC), vimentin were detected by Q-PCR
      and Western blot. Nuclear protein expression and activity of NFATc1 were detected
      by immunofluorescence and Western blot. Transwell assay was performed to measure
      the migration of VSMCs. Results: According to Western blot, the expression of
      NFATc1 and vimentin was significantly upregulated (5.07+/-0.36 vs. 1.00+/-0.00,
      P<0.05; 3.23+/-0.27 vs. 1.00+/-0.00, P<0.05) while alpha-SMA and SM-MHC
      expressions was significantly downregulated (0.73+/-0.15 vs. 1.00+/-0.00, P<0.05;
      0.45+/-0.05 vs. 1.00+/-0.00, P<0.05) in CD137 agonist group compare to control
      group. Compared with CD137 agonist group, the expression of NFATc1 and vimentin
      was significantly downregulated (1.56+/-0.27 vs. 5.07+/-0.36, P<0.05; 1.21+/-0.17
      vs. 3.23+/-0.27, P<0.05), but the levels of alpha-SMA and SM-MHC were
      significantly upregulated (2.01+/-0.43 vs. 0.73+/-0.15, P<0.05; 2.85 +/-0.32 vs.
      0.45+/-0.05, P<0.05) in anti-CD137 group. Compared with si-con group, the
      expression of SM-MHC and alpha-SMA was significantly upregulated while the
      expression of vimentin was significantly downregulated in si-NFATc1 group.
      Transwell assay results demonstrated that migration cell numbers was
      significantly higher in CD137L group compared with control group(3.85+/-0.31 vs.
      1.00+/-0.00, P<0.05), this effect was significantly attenuated by inhibiting
      NFATc1. Conclusion: CD137 could induce VSMC phenotype transformation through
      activating NFATc1 signaling.

PMID- 29036982
TI  - [Research advances on the relationship between nitrate-nitrite-NO pathway and
      heart failure with preserved ejection fraction].

PMID- 29036983
TI  - [Research progress on the treatment of pulmonary arterial hypertension with
      treprostinil].

PMID- 29036984
TI  - [Depression and cardiovascular disease].

PMID- 29036985
TI  - [Cardiac troponin I-interacting kinase: a new intervention target for ventricular
      remodeling].

PMID- 29036986
TI  - [Antimicrobial resistance spread and genes transfer].

PMID- 29036987
TI  - ["Internet+"dietary assessment becomes the innovative technology of nutrition
      work].

PMID- 29036988
TI  - [Characteristics of molecular typing and drug resistance of 67 Salmonella
      paratyphi A isolated in Zhengzhou from 2013 to 2015].
AB  - Objective: To investigate the antimicrobial resistance and pulsed field gel
      electrophoresis (PFGE) patterns of S.paratyphi A strains in Zhengzhou city
      isolated from sentinel hospitals in 2013-2015. Methods: According to Salmonella
      molecular typing and K-B drug susceptibility testing method published by
      international PulseNet bacterial infectious disease monitoring network and USA
      Clinical and Laboratory Standards Institute (CLSI2015), we analyzed drug
      sensitivity and PFGE molecular characteristics of 67 S.paratyphi A strains(11
      strains in 2013, 7 strains in 2014, 49 strains in 2015) isolated from blood and
      stool samples in two sentinel hospitals of fever with rash syndrome surveillance
      system established in Zhengzhou city in 2013-2015. Results: The results showed 67
      strains of S.paratyphi A had different levels of resistance to 13 kinds of
      antibiotics, 65 strains were multi-drug resistant strains (97.0%), 5 isolates
      were resistant to 2-3 kinds of antibiotics (7.5%), 41 isolates were resistant to
      5-8 kinds of antibiotics (61.2%),11 isolates were resistant to 9-10 kinds of
      antibiotics(16.4%),8 isolates were resistant to 11-12 kinds of
      antibiotics(11.9%). 67 strains of S.paratyphi A were divided into 10 molecular
      patterns(PTYA1-PTYA10) by digestion with XbaI restriction endonuclease and pulsed
      field gel electrophoresis, each pattern contains 1-48 strains with similarity
      ranged from 94.31%-100%. PTYA3 contained 48 strains, which was predominant band
      type; PTYA1, 9 contained 6 strains; PTYA 2, 4, 5, 6, 7, 8, 10 contained 1 strains
      among them. Conclusion: The status of drug resistance of clinical isolates of
      S.paratyphi A in Zhengzhou city was rather serious, PFGE patterns showed
      diversity and dominant characteristics. The PFGE patterns of partial strains and
      its corresponding anti-drug spectrum have certain relevance and cluster
      relationship.

PMID- 29036989
TI  - [Dissemination of insertion sequence common regions 1 and int1 gene and drug
      resistance of 483 Escherichia coli and Klebsiella pneumonia broiler isolates].
AB  - Objective: To investigate and analyze distribution characteristics of two
      multidrug resistance related genes in broiler isolates in Shandong province.
      Methods: The pre slaughter broilers were chosen from Shandong province in this
      study in June, 2014. A total of 400 fecal samples from five different zones
      (east, south, west, north and middle) of the hen house were collected. 373(77.2%)
      Escherichia coli and 110 (22.8%) Klebsiella pneumonia strains were isolated, and
      ISCR1 and int1 gene were detected by PCR assay and sequencing. The resistance to
      10 drugs belonging to 8 classes antimicrobial drugs were obtained by using
      minimal broth dilution method and data analysis. The difference between isolates
      and drug resistance profiles was analyzed. Results: Among 483 isolates, 440
      isolates (91.1%), 126 isolates (26.1%) and 126 isolates (26.1%) were detected as
      int1, ISCR1 and both two gene carriers, respectively. The rate of 37 E. coli
      isolates not carried ISCR1 or int1 gene resistant to 0 to 2, 3 to 5, 6 to 8
      classes antimicrobial agents was 13.5% (n=5), 78.4% (n=29), and 8.1% (n=3),
      respectively; the rate of 288 only int1 gene E. coli carriers resistant to 0 to
      2, 3 to 5, 6 to 8 groups antimicrobial agents was 2.4% (n=7), 74.7% (n=215), and
      22.9% (n=6), respectively. The data above showed significant difference
      (P<0.001). The rate of 26 only int1 gene K. pneumonia carriers resistant to 0 to
      2, 3 to 5, 6 to 8 classes antimicrobial agents was 11.5% (n=3), 76.9% (n=20), and
      11.5% (n=3), respectively; the rate of 78 both two gene K. pneumonia carriers
      resistant to0 to 2, 3 to 5, 6 to 8 groups antimicrobial agents was 0, 35.9%
      (n=28), and 64.1% (n=50), respectively. The data above showed significant
      difference (P<0.001). Conclusion: Gene int1 and ISCR1 showed high prevalence in
      E. coli and K. pneumonia isolates. High level multi-drug resistance profile could
      be mediated by int1 and ISCR1 gene co-existence.

PMID- 29036990
TI  - [Drug resistance and dissemination of New Delhi metallo-beta-lactamase 1 positive
      bacteria in a patient].
AB  - Objective: The aim of this work was to report the surveillance and dissemination
      of NDM-1 positive bacteria in a patient and ward environment. Methods: In 2010,
      during the therapy for a 51 years old patient, clinical and environmental samples
      were collected for carbapenem resistant bacterial culture, according to the
      clinical microbiological examination. Strains identification and antibiotic
      susceptibility were tested by VITEK Compact 2 system and E-test. The bla(NDM-1)
      was detected by PCR and analyzed by sequencing. Plasmids containing bla(NDM-1)
      were submitted to PFGE-S1 and Southern hybridization. Results: During
      hospitalization from October 1st to November 4th, nine strains were isolated from
      blood, sputum, urine, fecal, and ward ground samples. The Klebsiella oxytoca,
      Raoultella planticola, and Acinetobacter baumannii were isolated from blood
      sample. The Klebsiella pneumonia and Acinetobacter baumannii were isolated from
      sputum sample. An Acinetobacter lwoffii was isolated from urine sample. An
      Escherichia coli was isolated from fecal sample. And the Acinetobacter lwoffii
      and Acinetobacter spp. were isolated from ward ground. Four strains were NDM-1
      positive, which were Raoultella planticola (RpNDM1) isolated from blood,
      Escherichia coli (EcNDM1) isolated from fecal, Acinetobacter lwoffii (AlDNM1) and
      Acinetobacter spp. (AsNDM1) isolated from ward ground. Four NDM-1 positive
      strains were resistant to Piperacillin, Piperacillin tazobactam, Cefepime,
      Ceftriaxone, Ceftazidime, Imipenem, Meropenem, and Ertapenem. Southern
      hybridization revealed that bla(NDM-1) were all located on plasmids in the four
      positive strains. Conclusion:bla(NDM-1) can transfer rapidly among different
      species, resulting in difficult to control and prevent. While isolating patient
      who is carrying NDM-1 positive strains, more attention should be paid to the
      disposal of patient's excreta, especially stool, should be paid more attention.

PMID- 29036991
TI  - [Molecular epidemiology of carbapenem resistant Klebsiella pneumoniae in a
      hospital in Beijing].
AB  - Objective: To reveal the molecular epidemiological characteristics of Carbapenem
      Resistant Klebsiella pneumoniae (CRKP) isolated from a three level teaching
      hospital in Beijing. Methods: Pulsed field gel electrophoresis (PFGE) was carried
      out to subtyping 375 CRKP isolated in that hospital between May 2010 and October
      2015. Fifteen strains were chose based on the PFGE patterns to be analyzed by
      multi-locus sequence typing (MLST) and detection of carbapenem-resistance genes.
      One strain (A1502) was selected for whole genome sequencing and analyzing.
      Results: The 375 CRKP were divided into 140 PFGE types, among which five types
      contained more than five strains. The dominant types were distributed in
      different time periods and wards. Among the 15 strains tested by MLST and
      carbapenem-resistance genes detection, 13 were ST11 strains carrying KPC-2 gene.
      By genome-based typing, A1502 was clustered together with strains from other
      hospitals of Beijing but far from the strains from Shanghai and Hangzhou.
      Conclusion: The CRKP epidemic clone (ST11 clone carrying KPC-2) has been
      spreading within single hospital and across different hospitals in Beijing.

PMID- 29036992
TI  - [Survey on burden of disease attributable to low fruit intake among Chinese
      people aged 15 years old and above between 1990 and 2013].
AB  - Objective: To analyze the burden of disease attributable to low fruit intake
      among Chinese population aged >=15 years old between 1990 and 2013. Methods: We
      used data from the 2013 Global Burden of Disease Burden of Disease Study to study
      the situation in China. The population attributable fraction was calculated to
      estimate and compare the death and disability-adjusted life years (DALY)
      attributed to low fruit intake between 1990 and 2013 in China (excluded Taiwan,
      China). An average world population age structure of the period 2000-2025 was
      adopted to calculate age-standardized rates. Results: Deaths attributable to low
      fruit intake accounted for 11.02% of all death in 2013, which were higher than it
      in 1990 (10.38%). In 2013, the number of deaths attributed to low fruit intake in
      China increased to 1 046 500 from 793 800 in 1990. From 1990-2013, the age
      standardized death rate attributable to low fruit intake decreased from
      113.04/100 000 to 79.80/100 000. DALYs caused by low fruit intake increased from
      18.346 5 million in 1990 to 21.296 7 million in 2013. Compared with 1990, the age
      standardized DALY rate attributed to low fruit intake decreased by 34.67%. In
      2013, the top three provinces with the highest burden of disease attributed to
      low fruits intake were Tibet, Guizhou and Xinjiang provinces, with standardized
      DALY rate at 2 612.53/100 000, 2 281.85/100 000 and 2 198.22/100 000,
      respectively. Compared with the results in 1990, the standardized DALY attributed
      to low fruits intake decreased, especially in Tianjin, where decreased by 63.61%;
      followed by Aomen, Zhejiang, Shanghai and Beijing, where decreased by 59.74%,
      59.53%, 56.64% and 53.88%, respectively. Conclusion: Compared with the situation
      in 1990, the burden of disease attributable to low fruit intake decreased in
      2013, but the situation is still serious, especially in Tibet, Guizhou and
      Xinjiang provinces, where the burden decreased comparatively slowly.

PMID- 29036993
TI  - [Study on the disease burden of Chinese adolescent in 2015].
AB  - Objective: To discuss the main causes and risk factors of disability and death
      among current Chinese adolescents. Methods: Subnational data of China from Global
      Burden of Disease Study 2015 (GBD 2015) was used to rank the causes and risk
      factors leading to death and disability adjusted life years (DALY) in Chinese
      adolescents aged between 10 and 19 years old, and thereby to analyze the main
      cauese and risk factors of death and DALY among Chinese adolescents in different
      genders. Results: In 2015, among Chinese adolescents aged 10-19 years old, the
      total DALY was 13 million 490 thousand years, and the total number of deaths was
      63 258 cases. The top 3 causes of DALY were skin and subcutaneous diseases, iron
      deficiency anemia and road injuries, resulting in DALY (constituent ratio) of 1
      411 (10.5%), 1 094 (8.1%) and 1 029 (7.6%) thousand years respectively. The top 3
      causes of death were road injuries, drowning and leukemia, causing 13 881
      (21.9%), 9 895 (15.6%) and 4 620 (7.3%) deaths (constituent ratio) respectively.
      The top 3 risk factors of DALY were iron deficiency, alcohol use and drug use,
      causing 1 094 (8.1%), 487 (3.6%) and 220 thousand years (1.6%) DALY (constituent
      ratio) respectively. The top 3 risk factors of death were alcohol use,
      occupational injuries and drug use, causing 5 957 (9.4%), 1 523 (2.4%) and 810
      (1.3%) deaths respectively. Conclusion: Unintentional injury was the top cause of
      DALY and death in Chinese adolescents, followed by skin and subcutaneous diseases
      and iron-deficiency anemia. Iron deficiency and alcohol use were the top two risk
      factors of DALY and death.

PMID- 29036994
TI  - [Trend analysis of the burden of ischemic heart disease in China, 1990 to 2015].
AB  - Objective: The objective of this study is to analyze the trend of burden of
      ischemic heart disease (IHD) in China between 1990 and 2015. Methods: Data were
      collected from the results of 2015 Global Burden of Disease Study. We arranged
      and analyzed the mortality and disability-adjusted life year (DALY) for IHD by
      sexes, ages and provinces (excluding Taiwan, China) in China between 1990 and
      2015. The age-standardized rates were determined using the average world
      population age structure in the period of 2010-2035 as a reference, and the
      changes of the related indicators were calculated. Results: In 2015, IHD caused 1
      461 thousand deaths, and its age-standardized death rate was 114.8 per 100 000.
      Number of DALYs from IHD were 25 765 thousand in 2015, with the age-standardized
      DALY rate at 1 760.2 per 100 000. From 1990 to 2015, the age-standardized death
      rate for IHD in China increased by 13.3% but age-standardized DALY rate decreased
      by 3.9%. Number of IHD DALYs among male (16 664 thousand) was higher than it
      among female (9 101 thousand) in China in 2015, and 83.5% of total DALYs from IHD
      occurred among people aged over 50 years old. Province with highest age
      standardized death rate was Heilongjiang, with rate at 187.4 per 100 000 in 2015.
      Qinghai (54.0%) increased most and Macao (-52.3%) decreased most from 1990 to
      2015. Province with highest age-standardized DALY rate was Xinjiang, with rate at
      3 040.8 per 100 000 in 2015. Qinghai (33.2%) increased most while Macao (-59.0%)
      decreased most between 1990 and 2015. Conclusion: Burden of IHD in China
      increased remarkably from 1990 to 2015, especially among males and people aged
      over 50 years old. The differences among provinces were obvious.

PMID- 29036995
TI  - [Association of alcohol use and incidence of type 2 diabetes mellitus in the
      middle-aged and elderly male population: a prospective cohort study].
AB  - Objective: To investigate the association between alcohol use and incidence of
      type 2 diabetes mellitus (T2DM) in the middle-aged and elderly male population.
      Methods: All participants were from Dongfeng-Tongji cohort, 27 009 retired
      employees from Dongfeng Motor Corporation in Hubei Province were enrolled in the
      Dongfeng-Tongji cohort baseline survey in 2008. In baseline study, information of
      alcohol use and other covariates were collected by semi-structured questionnaire
      and all participants completed physical examination including the test of fasting
      glucose and blood lipid levels. A total of 6 784 male participants from Dongfeng
      Tongji cohort who were without diagnosis of diabetes, coronary heart disease,
      stroke, or cancer in baseline study were enrolled in this study. We completed the
      first follow-up in 2013 and the outcome of disease or death was retrieved based
      on health-care medical records according to the unique medical insurance ID. Cox
      proportional hazard regression model was used to estimate the association between
      alcohol use and incidence of type 2 diabetes mellitus (T2DM), by drinking
      features and patterns. Results: Out of the 6 784 participants, 3 541 participant
      were defined as non-alcohol drinkers and there were 15 852.2 person-years of
      follow-up; among which 270 new cases of T2DM were diagnosed withthe crude
      incidence density of non-alcohol drinkers at 1 703.2/100 000 person-years. The
      other 3 243 subjects were classified as alcohol drinkers and there were 14 509.8
      person-years of follow-up; and among which 258 new cases of T2DM were diagnosed,
      with the crude incidence density of T2DM at 1 778.1/100 000 person-years.
      Multivariate COX proportional hazard regression model indicated that there was no
      significantly increased risk of T2DM incidence between alcohol drinkers and non
      alcohol drinkers(HR(95% CI): 1.09 (0.91- 1.30)). However, participants who
      averagely consumed >20 g/d or>7 times/week had a significantly increased risk of
      T2DM compared with non-alcohol drinkers, and the value of HR(95%CI) was 1.27
      (1.02- 1.58) and 1.35 (1.00- 1.83), respectively. Among men who consumed
      alcoholic beverages more than 7 times/week, HR (95%CI) for T2DM incidence in the
      subjects who consumed 0.01 to 40 g and > 40 g once a time were 1.48 (1.05- 2.09)
      and 1.27 (0.80- 2.10), respectively. Conclusion: Although we found no
      relationship between alcohol use and T2DM incidence overall, alcohol use more
      than 20 g/d or more than 7 times/week would increase the risk of T2DM.

PMID- 29036996
TI  - [Analysis of prevalence and related factors of osteoporosis in retired population
      based on Dongfeng-Tongji Cohort].
AB  - Objective: To investigate the prevalence and related factors of osteoporosis
      among retired population in Dongfeng-Tongji cohort. Methods: 27 009 retired
      participants were recruited from Dongfeng Motor Corporation in Hubei Province in
      2008 and followed up from April to October in 2013. newly retired participants
      also were recruited. Data were collected by using questionnaire, physical
      examination, serum hepatase detection and bone densitometry. Totally, 30 916
      participants were included for data analysis after excluding participants with
      severe bone metabolic diseases, taking hormone drugs, incomplete follow-up data
      and who were under 45 years old. Age-standardized prevalence of osteoporosis was
      calculated according to data of the 2010 Sixth National Population Census.
      Multivariate logistic regression analysis was applied to explore the associated
      factors of osteoporosis. Results: Prevalence of osteoporosis was 42.3% (13 083/30
      916) and age standardized prevalence was 40.7%: 35.0% (4 854/13 878) and 34.8%
      for males; 48.3% (8 229/17 038) and 47.1% for females. Significantly associated
      factors with osteoporosis for both males and females included: older age (male:
      OR=1.67, 95%CI: 1.40-1.99; female:OR=3.34, 95%CI: 2.70-4.13), lower BMI (male:
      OR=1.70, 95%CI: 1.40-2.06; female: OR=1.27, 95%CI: 1.04-1.53), exercise (male:
      OR=0.69, 95%CI: 0.61-0.78; female: OR=0.87, 95%CI: 0.80-0.96), abnormal elevated
      serum alkaline phosphatase (ALP) (male: OR=1.12, 95%CI: 1.01-1.24; female:
      OR=1.15, 95%CI: 1.06-1.25), gamma-glutamyltransferase (gamma-GT) (male: OR=1.16,
      95%CI: 1.02-1.30; female: OR=1.13, 95%CI: 1.03-1.24) and aspartate
      transaminase/alanine aminotransferase (AST/ALT) (male: OR=1.15, 95%CI: 1.05-1.25;
      female: OR=1.28, 95%CI: 1.19-1.38). Smoking (OR=1.27, 95%CI: 1.07-1.39) and
      drinking (OR=1.11, 95%CI: 1.08-1.16) were associated factors for males while
      menopausal (OR=1.67, 95%CI: 1.47-1.89) for females. There were positive dose
      response correlation relationships of serum levels of ALP, gamma-GT and AST/ALT
      with osteoporosis (all P values<0.05). Conclusion: Osteoporosis was relatively
      common among retired population in Dongfeng-Tongji cohort. In addition to known
      factors such as older age, lower BMI and exercise, abnormal elevated serum ALP,
      gamma-GT and AST/ALT were also associated with osteoporosis.

PMID- 29036997
TI  - [Mean blood pressure among the adults in China 2010-2012: based on the results of
      mercury sphygmomanometer and converted electronic sphygmomanometer].
AB  - Objective: To analyze the average systolic blood pressure (SBP) and diastolic
      blood pressure (DBP) among adults aged 18 years old and above in China between
      2010 and 2012; and to compare the difference in the results measured by mercury
      sphygmomanometer and converted electronic sphygmomanometer. Methods: The data was
      collected from Chinese Nutrition and Health Surveillance in 2010-2012. 120 428
      adults aged 18 years old and above were selected from 150 survey counties
      (districts) of 31 provinces in China Mainland, by multi-stage stratified and
      probability proportion to size (PPS) cluster randomization sampling method. The
      average blood pressure value was calculated from three systolic and diastolic
      blood pressure readings measured by mercury sphygmomanometer. The value of
      Electronic Sphygmomanometer was converted by regression formula. Age-standardized
      results were calculated incorporating a complex sample weighting using the
      population data from the National Bureau of Statistics in 2009. Results: The
      overall adjusted mean of SBP based on the value of mercury sphygmomanometer among
      Chinese adults aged 18 years old and above was 122 mmHg (1 mmHg=0.133 kPa), 124
      mmHg in men and 120 mmHg in women. The average SBP value was separately 115, 127,
      and 137 mmHg in groups of adults aging 18-44, 45-59 and >=60 years old. The
      average SBP was 122 mmHg in urban and 122 mmHg in rural areas. Mean DBP was 78
      mmHg, 79 mmHg in men and 76 mmHg in women. The average DBP was separately 75, 81,
      and 81 mmHg in groups of adults aging 18-44, 45-59 and >=60 years old. The
      average DBP was 78 mmHg in urban and 77 mmHg in rural areas. The overall adjusted
      mean of SBP based on converted electronic device was 129 mmHg,130 mmHg in men and
      127 mmHg in women, respectively. The mean of SBP was separately122, 134, and 143
      mmHg in groups of adults aging 18-44, 45-59 and >=60 years old. Mean SBP was both
      129 mmHg in urban and in rural areas. Mean DBP was 76 mmHg, 78 mmHg in men and 75
      mmHg in women, respectively. The average DBP was separately 74, 79, and 79 mmHg
      in groups of adults aging 18-44, 45-59 and >=60 years old. The average DBP was
      both 76 mmHg in urban and rural areas. Conclusion: The average SBP and DBP was
      different between the mercury sphygmomanometer and converted electronic device.
      However, the results from both measures showed that the blood pressure was higher
      in men than in women, the blood pressure increased with the increase of age, and
      there was no difference between urban and rural areas.

PMID- 29036998
TI  - [Association between polymorphism of rs10185316 in insulin-induced gene 2 and
      blood pressure among children and adolescents].
AB  - Objective: To examine the association between polymorphism of rs10185316 in
      insulin-induced gene 2 (INSIG2) and blood pressure among children and
      adolescents. Methods: 9 junior middle schools in Dongcheng District of Beijing
      and 5 schools (3 primary junior middle schools, 2 primary schools) in Haidian
      District of Beijing were chosen in 2005 and 2007, respectively. According to the
      Chinese BMI percentile criteria for screening overweight and obesity in school
      children, we recruited 1 425 overweight or obese children and 605 normal weight
      children. A total of 2 018 students with complete data of blood pressure and
      genotype data were included in this study. According to the blood pressure
      criterion of children and adolescents, 702 participants were categorized into
      high blood pressure group and 1 316 into normal blood pressure group.
      Participants' information of gender, age, height, weight and blood pressure were
      collected by questionnaire and physical examination. Genomic DNA was extracted
      from peripheral blood sample for genotyping of INSIG2 rs10185316 polymorphism.
      Multiple linear regression was conducted to analyze the associations between
      rs10185316 polymorphism in INSIG2 and SBP, DBP, mean arterial pressure (MAP) and
      pulse pressure. Results: The age, BMI, SBP and DBP of the high blood pressure
      group were separately (14.3+/-1.4) years old, (27.3+/-4.2) kg/m(2), (130.5+/
      10.9) and (76.7+/-13.3) mmHg (1 mmHg=0.133 kPa), all higher than that of the
      normal blood pressure group, which were (12.2+/-2.9) years old, (22.0+/-4.0)
      kg/m(2), (104.4+/-10.9) and(54.6+/-15.2) mmHg, respectively (all P values<0.001).
      After age, sex, district and BMI adjusted, compared with the participants
      carrying INSIG2 rs10185316 CC genotype, CG/GG genotype carriers had lower DBP
      (beta(95%CI):-1.67(-2.84--0.50), P=0.005), higher PP(beta(95%CI): 1.91(0.61
      3.20), P=0.004), and lower MAP(beta(95%CI):=-1.03(-2.01--0.05), P=0.039).
      Conclusion: INSIG2 rs10185316 polymorphism was associated with DBP, PP and MAP
      among children and adolescents in an independent way from BMI.

PMID- 29036999
TI  - [The contamination and dietary exposure analysis for seven mycotoxins in the
      Fifth Chinese Total Diet Study].
AB  - Objective: To investigate the contamination levels and dietary intakes of seven
      mycotoxins in Chinese diets. Methods: In Chinese Total Diet Study, food
      aggregation was based on the food consumption of local residents, thus generating
      the sampling scheme. According to the sampling scheme, the food items were
      sampled at three survey points in each province and then mixed in the same
      proportion. The mixed dietary samples were prepared after being cooked and
      processed. The samples comprised of 13 categories of food: cereals, beans,
      potatoes, meat, eggs, aquatic products, milk, vegetables, fruits, saccharides,
      beverages and drinking water, alcohol, and condiments. Condiments were used in
      cooking, so there were in total 12 varieties of samples for determination.
      Altogether, the study included 240 mixed dietary samples from 20 provinces with
      12 varieties. The contamination levels of the seven mycotoxins, including
      sterigmatocystin (SMC), citrinin (CIT), cyclopiazonic acid (CPA), moniliformin
      (MON), gliotoxin (GLIO), mycophenolateacid (MPA) and verruculogen (Verru), were
      analyzed by UPLC-MS/MS method, and dietary intakes of residents were estimated as
      well. Results: Among the detected seven mycotoxins, MPA,GLIO and Verru were not
      detected. The content range of CPA in beans was 0.47-1.57 MUg/kg and in alcohol
      was 0.19-2.26 MUg/kg, and the detection rate of CPA was 7.1% (17/240). The
      content of SMC in aquatic products of Guangxi, in saccharides of Beijing, and in
      beverages of Liaoning was 2.88 MUg/kg, 0.01 MUg/kg, and 0.53 MUg/kg,
      respectively. The content range of SMC in aquatic products was 0.70-1.76 MUg/kg,
      and the detection rate was 2.9% (7/240). In addition, the content of CIT in fruit
      of Sichuan was 5.31 MUg/kg, and the content of MON in milk of Jilin was 3.60
      MUg/kg. According to the dietary exposure analysis, the exposure levels of the
      seven mycotoxins in China's general population were low. MPA, GLIO and Verru were
      not detected, and the exposure range of the other four mycotoxins were 0.000
      8.132 (CIT), 0.000-27.448 (SMC), 0.000-3.026 (CPA), and 0.000-62.847 ng.kg(-1).d(
      1) (MON), respectively. Conclusion: In the detected seven mycotoxins, CPA, SMC,
      CIT and MON were detected only in the individual diet in some areas with a low
      dietary exposure level. However, the contamination level of CPA in alcohol merits
      attention.

PMID- 29037000
TI  - [Analysis of fipronil and metabolites residues distrubution in eggs].
AB  - Objective: To compare the residual distribution of fipronil and its metabolites
      in white and yellow egg, and to analyze the residual changes of fipronil and its
      metabolites in raw and cooked samples, regarding the risk assessment of fipronil
      and its metabolites via consuming egg for different age groups. Methods: The
      white egg and yellow egg were isolated from 10 egg samples containing fipronil
      residues. Samples were extracted with acetonitrile and purified, and determined
      by liquid chromatography-high resolution mass spectrometry. The chromatographic
      analysis was performed on a BEH C(18) column with 0.1% acetic acid and
      acetonitrile as mobile phase with gradient elution, and external standard
      calibration was used for quantification. The negative ion acquisition mode was
      applied and quantitative analysis was carried out by using Full Scan/ddms2 model.
      Results: The results showed that fipronil sulfone was the main residue detected
      in eggs; The content of fipronil sulfone in white egg was between 2.5 and 59.9
      MUg/kg, the median was 16.1 MUg/kg; and the content of fipronil sulfone in yellow
      egg ranged from 81.5 and 1 526.0 MUg/kg, with a median of 390.0 MUg/kg. The ratio
      of fipronil sulfone in yellow egg to white egg ranged from 8.0 and 14.6. Compared
      with that observed in fresh egg, after heating or cooking, the content ratio of
      fipronil sulfone residue between cooked samples and raw samples from yellow egg
      was between 0.80 and 0.96, the median was 0.90; and the ratio from white egg
      ranged from 0.65 to 1.06, the median was 0.83. The conversion coefficient of
      fipronil sulfone (f) between white egg and yellow egg was 3.1. Conclusion: Yellow
      egg is a major intake source of fipronil and metabolites residues, and there is
      no obvious change for fipronil sulfone residue in eggs after heating or cooking.
      The conversion coefficient of fipronil sulfone (f) between white egg and yellow
      egg lays the foundation for assessing the health risks of fipronil and
      metabolites residues through yellow egg intake in special population.

PMID- 29037001
TI  - [Analysis of the characteristics and HIV/syphilis/HCV infection among new
      narcotic users in Beijing, 2010-2016].

PMID- 29037002
TI  - [The usage guidance of blood pressure reference in the fourth report on the
      diagnosis, evaluation, and treatment of high blood pressure in children and it's
      SPSS program].

PMID- 29037003
TI  - Effects of Temperature and Pressure on Acute Stroke Incidence Assessed Using a
      Korean Nationwide Insurance Database.
AB  - BACKGROUND AND PURPOSE: Many studies have evaluated the association between
      weather and stroke, with variable conclusions. Herein we determined the
      relationships between daily meteorological parameters and acute stroke incidence
      in South Korea. METHODS: Patients with acute stroke (2,894) were identified by
      standard sampling of a nationwide insurance claims database from January to
      December 2011. We used multiple Poisson regression analyses of stroke incidence
      and meteorological parameters (mean temperature, diurnal temperature change,
      temperature differences over the preceding 24 hours, atmospheric pressure,
      humidity, wind speed, and physiologically equivalent temperature) to calculate
      the relative risk of stroke incidence associated with meteorological parameters.
      RESULTS: There were no seasonal variations in the incidences of ischemic (2,176)
      or hemorrhagic (718) stroke. Temperature change during the day was positively
      correlated with ischemic stroke in men (relative risk [RR] 1.027; 95% confidence
      interval [CI] 1.006-1.05) and older patients (>=65 years) (RR 1.031, 95% CI 1.011
      1.052). Temperature differences over the preceding 24 hours had a negative
      correlation with all strokes (RR 0.968, 95% CI 0.941-0.996), especially among
      older women. Diurnal variation of atmospheric pressure was also significantly
      associated with the incidence of ischemic stroke (age<65 years, RR 1.051, 95% CI
      1.011-1.092; age>=65 years, RR 0.966, 95% CI 0.936-0.997). CONCLUSIONS: Diurnal
      temperature change, temperature differences over the preceding 24 hours, and
      diurnal variation of atmospheric pressure were associated with daily stroke
      incidence. These findings may enhance our understanding of the relationship
      between stroke and weather.

PMID- 29037004
TI  - Association of Systolic Blood Pressure with Progression of Symptomatic
      Intracranial Atherosclerotic Stenosis.
AB  - BACKGROUND AND PURPOSE: Elevated blood pressure (BP) is associated with greater
      severity of intracranial atherosclerotic stenosis (ICAS) and increased risk of
      ischemic stroke. Because little is known about the relationship of maintained BP
      level with progression of symptomatic ICAS (sICAS), we evaluated the independent
      association of maintained systolic BP (SBP) with risk of sICAS progression.
      METHODS: We analyzed the Trial of cilOstazol in Symptomatic intracranial Stenosis
      2, which evaluated 402 stroke patients with sICAS (mean age, 64.5+/-11.3 years;
      male, 52.2%). Study participants were categorized into four groups according to
      mean SBP level: low-normal (<120 mm Hg), normal to high-normal (120 to 139 mm
      Hg), high (140 to 159 mm Hg), and very-high (>=160 mm Hg). Progression of sICAS
      was defined as worsening in the degree of stenosis by >=1 grade on the 7-month
      magnetic resonance angiography follow-up. RESULTS: sICAS progression was observed
      in 52 (12.9%) subjects. Percentages of sICAS progression by mean SBP category
      showed a J-shape pattern: low-normal (21.4%), normal to high-normal (10.7%), high
      (11.4%), and very-high (38.9%). In multivariable analysis, compared to the normal
      to high-normal SBP group, odds ratios (95% confidence intervals) were low-normal,
      1.88 (0.62-5.67); high, 1.06 (0.47-2.37); and very-high, 8.75 (2.57-29.86). Rate
      of sICAS progression by 10-mm Hg strata showed a similar pattern to findings from
      mean SBP category (9.47; 2.58-34.73 for SBP >=160 mm Hg). CONCLUSIONS: Among
      individuals with a recent ICAS stroke, very-high SBP level during the short-term
      period after the index stroke was associated with significantly greater odds of
      sICAS progression.

PMID- 29037005
TI  - Stroke Epidemiology in South, East, and South-East Asia: A Review.
AB  - Asia, which holds 60% of the world's population, comprises some developing
      countries which are in economic transition. This paper reviews the epidemiology
      of stroke in South, East and South-East Asia. Data on the epidemiology of stroke
      in South, East, and South-East Asia were derived from the Global Burden of
      Disease study (mortality, disability-adjusted life-years [DALYs] lost because of
      stroke), World Health Organization (vascular risk factors in the community), and
      publications in PubMed (incidence, prevalence, subtypes, vascular risk factors
      among hospitalized stroke patients). Age- and sex-standardized mortality is the
      lowest in Japan, and highest in Mongolia. Community-based incidence data of only
      a few countries are available, with the lowest rates being observed in Malaysia,
      and the highest in Japan and Taiwan. The availability of prevalence data is
      higher than incidence data, but different study methods were used for case
      finding, with different age bands. For DALYs, Japan has the lowest rates, and
      Mongolia the highest. For community, a high prevalence of hypertension is seen in
      Mongolia and Pakistan; diabetes mellitus in Papua New Guinea, Pakistan, and
      Mongolia; hypercholesterolemia in Japan, Singapore, and Brunei; inactivity in
      Malaysia; obesity in Brunei, Papua New Guinea, and Mongolia; tobacco smoking in
      Indonesia. Hypertension is the most frequent risk factor, followed by diabetes
      mellitus and smoking. Ischemic stroke occurs more frequently than hemorrhagic
      stroke, and subarachnoid hemorrhages are uncommon. There are variations in the
      stroke epidemiology between countries in South, East, and South-East Asia.
      Further research on stroke burden is required.

PMID- 29037007
TI  - Small Vessel Transient Ischemic Attack and Lacunar Infarction Detected with
      Perfusion-Weighted MRI.

PMID- 29037006
TI  - MicroRNA 150-5p Improves Risk Classification for Mortality within 90 Days after
      Acute Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Micro ribonucleic acid-150-5p (miR-150-5p) regulates
      proinflammatory cytokines as well as vessel integrity. We evaluated the
      incremental prognostic value of logarithm (log) of miR-150-5p plasma levels after
      ischemic stroke. METHODS: In a prospective cohort study, levels of miR-150-5p
      were measured within 72 hours of symptom onset in 329 ischemic stroke patients.
      The outcome measures were unfavorable functional outcome (assessed by the
      modified Rankin Scale score >2) and mortality within 90 days. Logistic regression
      and Cox proportional hazards models were fitted to estimate odds ratio (OR),
      respectively hazard ratio (HR) and 95% confidence interval (CI) for the
      association between log-miR-150-5p and the outcome measures. The discriminatory
      accuracy was assessed with the area under the receiver-operating-characteristic
      curve (AUC) and the incremental prognostic value was estimated with the net
      reclassification index. RESULTS: After adjusting for demographic and vascular
      risk factors, lower log-miR-150-5p levels were independently associated with
      mortality (HR 0.21 [95% CI, 0.08-0.51], P=0.001) but not functional outcome (OR
      1.10 [95% CI, 0.54-2.25], P=0.79). Adding log-miR-150-5p improved the
      discriminatory accuracy of the best multivariate model to predict mortality from
      an AUC of 0.91 (95% CI, 0.88-0.95) to 0.92 (95% CI, 0.88-0.96 Likelihood-ratio
      test-P<0.001), and resulted in a net reclassification index of 37.3% (95% CI,
      0.28-0.52). CONCLUSIONS: In patients with ischemic stroke, log-miR-150-5p is a
      novel prognostic biomarker, highly associated with mortality within 90 days,
      improving risk classification beyond traditional risk factors.

PMID- 29037008
TI  - Histopathological Findings of Intracranial Thrombi in Nonbacterial Thrombotic
      Endocarditis.

PMID- 29037009
TI  - Early Statins after Intravenous or Endovascular Recanalization Is Beneficial
      Regardless of Timing, Intensity, and Stroke Mechanism.

PMID- 29037010
TI  - Effects of Triflusal and Clopidogrel on the Secondary Prevention of Stroke Based
      on Cytochrome P450 2C19 Genotyping.
AB  - BACKGROUND AND PURPOSE: To compare the efficacy and safety of antiplatelet agents
      for the secondary prevention of ischemic stroke based on cytochrome P450 2C19
      (CYP2C19) polymorphisms. METHODS: This study was a prospective, multicenter,
      randomized, parallel-group, open-label, blind genotype trial. First time non
      cardiogenic ischemic stroke patients were enrolled and screened within 30 days.
      Participants were randomized to receive either triflusal or clopidogrel for
      secondary stroke prevention. The primary outcome was the time from randomization
      to first recurrent ischemic stroke or hemorrhagic stroke. RESULTS: The required
      sample size was 1,080 but only 784 (73%) participants were recruited. In patients
      with a poor CYP2C19 genotype for clopidogrel metabolism (n=484), the risk of
      recurrent stroke among those who received triflusal treatment was 2.9% per year,
      which was not significantly different from those who received clopidogrel
      treatment (2.2% per year; hazard ratio [HR], 1.23; 95% confidence interval [CI],
      0.60-2.53). In the clopidogrel treatment group (n=393), 38% had good genotypes
      and 62% poor genotypes for clopidogrel metabolism. The risk of recurrent stroke
      in patients with a good CYP2C19 genotype was 1.6% per year, which was not
      significantly different from those with a poor genotype (2.2% per year; HR, 0.69;
      95% CI, 0.26-1.79). CONCLUSIONS: Whilst there were no significant differences
      between the treatment groups in the rates of stroke recurrence, major vascular
      events, or coronary revascularization, the efficacy of antiplatelet agents for
      the secondary prevention of stroke according to CYP2C19 genotype status remains
      unclear.

PMID- 29037011
TI  - Visibility of CT Early Ischemic Change Is Significantly Associated with Time from
      Stroke Onset to Baseline Scan beyond the First 3 Hours of Stroke Onset.
AB  - BACKGROUND AND PURPOSE: Non-contrast brain computed tomography (NCCT) remains the
      most common imaging modality employed to select patients for thrombolytic therapy
      in acute ischemic stroke. The current study used the Alberta Stroke Program Early
      CT Score (ASPECTS) to identify early ischemic changes on brain NCCT imaging with
      the aim to investigate whether a relationship exists between time from symptoms
      onset to NCCT with the presence of early ischaemic change quantified by ASPECTS.
      METHODS: We studied 1,329 ischemic stroke patients who had NCCT within 8 hours of
      stroke onset. Patients were assessed to see if they had any ASPECTS lesion and if
      the rate of patients with a lesion increased with time using logistic regression.
      RESULTS: 30% patients had an ASPECTS <10 within the first 3 hours from symptom
      onset. Within the first 3 hours, the odds for a CT change (ASPECTS <10) per
      minute of time was 1.00 with 95% confidence interval (CI) (0.99 to 1.00)
      (P=0.266). After 3 hours, there was a significant increase in odds of ASPECTS <10
      with increasing time. The odds of being ASPECTS positive increased 1% (odds
      ratio=1.01) per 1 minute of time with 95% CI (1.00 to 1.01) (P=0.002).
      CONCLUSIONS: We have identified that prior to first 3 hours of stroke there was
      no effect of time on odds of CT ischemic change; after the first 3 hours of
      stroke the odds increased with increasing time to CT scan. The occurrence of
      early ischemic change may be a marker of time from stroke onset rather than
      severity.

PMID- 29037012
TI  - Medical Treatment of Intracranial Atherosclerosis: An Update.
AB  - For patients with symptomatic intracranial atherosclerosis (ICAS), antithrombotic
      agents are the mainstay of therapy. Anticoagulation (warfarin) is not widely used
      since it is not more effective than aspirin and carries a high risk of bleeding.
      New oral anticoagulants are showing promise, but their use has not been
      investigated in appropriate clinical trials. Since the recurrent stroke risk is
      high with aspirin monotherapy, dual antiplatelets are considered in the early
      stage of symptomatic ICAS. Based on the Clopidogrel in High-Risk Patients with
      Acute Nondisabling Cerebrovascular Events (CHANCE) and Stenting and Aggressive
      Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis
      (SAMMPRIS) results, aspirin plus clopidogrel has been recommended. However, this
      combination was not superior to aspirin monotherapy in patients with ICAS in the
      CHANCE substudy. Progression of ICAS is common, and it is associated with
      recurrent strokes. In the Trial of Cilostazol in Symptomatic Intracranial
      Arterial Stenosis (TOSS) study, aspirin plus cilostazol was more effective than
      aspirin monotherapy in preventing progression. The TOSS II trial showed that the
      overall change in stenosis was better with aspirin plus cilostazol than with
      aspirin plus clopidogrel. Aside from antithrombotic therapy, risk factor
      management is critical for secondary prevention, and high blood pressure is
      clearly linked to recurrent stroke. However, blood pressure may have to be
      cautiously managed in the early stage of stroke. Considering that ICAS is the
      major cause of stroke worldwide, further investigations are needed to establish
      optimal management strategies for patients with ICAS.

PMID- 29037013
TI  - Angioplasty, Stenting and Other Potential Treatments of Atherosclerotic Stenosis
      of the Intracranial Arteries: Past, Present and Future.
AB  - Although there is an intuitive appeal to treat symptomatic stenotic intracranial
      arteries with endovascular therapies such as angioplasty and stenting, current
      data from randomized trials show intensive medical therapy is far superior for
      preventing stroke. This is in large part due to the high risk of peri-procedural
      stroke from angioplasty and stenting. If angioplasty and stenting is to emerge as
      a proven treatment for intracranial stenosis, endovascular techniques will need
      to become much safer, identification of patients with intracranial stenosis who
      are at particularly high risk of stroke despite intensive medical therapy will
      need to be targeted, and well-designed randomized trials will be necessary to
      show endovascular therapy is superior to medical therapy in these high-risk
      patients.

PMID- 29037014
TI  - Deep into the Brain: Artificial Intelligence in Stroke Imaging.
AB  - Artificial intelligence (AI), a computer system aiming to mimic human
      intelligence, is gaining increasing interest and is being incorporated into many
      fields, including medicine. Stroke medicine is one such area of application of
      AI, for improving the accuracy of diagnosis and the quality of patient care. For
      stroke management, adequate analysis of stroke imaging is crucial. Recently, AI
      techniques have been applied to decipher the data from stroke imaging and have
      demonstrated some promising results. In the very near future, such AI techniques
      may play a pivotal role in determining the therapeutic methods and predicting the
      prognosis for stroke patients in an individualized manner. In this review, we
      offer a glimpse at the use of AI in stroke imaging, specifically focusing on its
      technical principles, clinical application, and future perspectives.

PMID- 29037015
TI  - Comparison of Spot Sign, Blend Sign and Black Hole Sign for Outcome Prediction in
      Patients with Intracerebral Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Blend sign (BS) and black hole sign (BHS) on non-contrast
      computed tomography (NCCT) and spot sign (SS) on CT-angiography (CTA) are
      indicators of early hematoma expansion in spontaneous intracerebral hemorrhage
      (ICH). However, their independent contributions to outcome have not been well
      explored. METHODS: In this retrospective study, inclusion criteria were: 1)
      spontaneous ICH and 2) NCCT and CTA performed on admission within 6 hours after
      onset of symptoms. Discharge outcome was dichotomized as good (modified Rankin
      Scale [mRS] 0-3) and poor (mRS 4-6) outcomes. The impacts of BHS, BS and SS on
      outcome were assessed in univariate and multivariable logistic regression models.
      RESULTS: Of 182 patients with spontaneous ICH, 26 (14.3%) presented with BHS, 37
      (20.3%) with BS and 39 (21.4%) with SS. There was a substantial correlation
      between SS and BS (kappa=0.701) and a moderate correlation between SS and BHS
      (kappa=0.424). In univariable logistic regression, higher baseline hematoma
      volume (P<0.001), intraventricular hemorrhage (P=0.002) and the presence of
      BHS/BS/SS (all P<0.001) on admission CT scan were associated with poor outcome.
      Multivariable analysis identified intraventricular haemorrhage (odds ratio [OR]
      2.22 per mL, P=0.022), baseline hematoma volume (OR 1.03 per mL, P<0.001) and SS
      on CTA (OR 11.43, P<0.001) as independent predictors of poor outcome, showing
      that SS compared to BS and BHS was more powerful to predict poor outcome.
      CONCLUSIONS: The NCCT BHS and BS are correlated with the CTA SS and are reliable
      predictors of poor outcome in patients with ICH. Of the CT variables indicating
      early hematoma expansion, SS on CTA was the most reliable outcome predictor.
      However, given their correlation with SS on CTA, BS and BHS on NCCT can be useful
      for predicting outcome if CTA is not obtainable.

PMID- 29037016
TI  - Intracranial Atherosclerosis: Where Are We Now?

PMID- 29037017
TI  - Preoperative chemoradiotherapy versus postoperative chemoradiotherapy for stage
      II-III resectable rectal cancer: a meta-analysis of randomized controlled trials.
AB  - PURPOSE: Whether preoperative chemoradiotherapy (CRT) is better than
      postoperative CRT in oncologic outcome and toxicity is contentious in prospective
      randomized clinical trials. We systematically analyze and compare the treatment
      result, toxicity, and sphincter preservation rate between preoperative CRT and
      postoperative CRT in stage II-III rectal cancer. MATERIALS AND METHODS: We
      searched Medline, Embase, and Cochrane Library from 1990 to 2014 for relevant
      trials. Only phase III randomized studies performing CRT and curative surgery
      were selected and the data were extracted. Meta-analysis was used to pool
      oncologic outcome and toxicity data across studies. RESULTS: Three randomized
      phase III trials were finally identified. The meta-analysis results showed
      significantly lower 5-year locoregional recurrence rate in the preoperative-CRT
      group than in the postoperative-CRT group (hazard ratio, 0.59; 95% confidence
      interval, 0.41-0.84; p = 0.004). The 5-year distant recurrence rate (p = 0.55),
      relapse-free survival (p = 0.14), and overall survival (p = 0.22) showed no
      significant difference between two groups. Acute toxicity was significantly lower
      in the preoperativeCRT group than in the postoperative-CRT group (p < 0.001).
      However, there was no significant difference between two groups in perioperative
      and chronic complications (p = 0.53). The sphincter-saving rate was not
      significantly different between two groups (p = 0.24). The conversion rate from
      abdominoperineal resection to low anterior resection in low rectal cancer was
      significantly higher in the preoperative-CRT group than in the postoperative-CRT
      group (p < 0.001). CONCLUSIONS: As compared to postoperative CRT, preoperative
      CRT improves only locoregional control, not distant control and survival, with
      similar chronic toxicity and sphincter preservation rate in rectal cancer
      patients.

PMID- 29037018
TI  - Role of fractionated radiotherapy in patients with hemangioma of the cavernous
      sinus.
AB  - PURPOSE: We performed this retrospective study to investigate the outcomes of
      patients with hemangioma of the cavernous sinus after fractionated radiotherapy.
      MATERIALS AND METHODS: We analyzed 10 patients with hemangioma of the cavernous
      sinus who were treated with conventional radiotherapy between January 2000 and
      December 2016. The median patient age was 54 years (range, 31-65 years), and 8
      patients (80.0%) were female. The mean hemangioma volume was 34.1 cm3 (range, 6.8
      83.2 cm3), and fractionated radiation was administered to a total dose of 50-54
      Gy with a daily dose of 2 Gy. RESULTS: The median follow-up period was 6.8 years
      (range, 2.2-8.8 years). At last follow-up, the volume of the tumor had decreased
      in all patients. The average tumor volume reduction rate from the initial volume
      was 72.9% (range, 18.9-95.3%). All 10 of the cranial neuropathies observed before
      radiation therapy had improved, with complete symptomatic remission in 9 cases
      (90%) and partial remission in 1 case (10%). No new acute neurologic impairments
      were reported after radiotherapy. One probable compressive optic neuropathy was
      observed at 1 year after radiotherapy. CONCLUSION: Fractionated radiotherapy
      achieves both symptomatic and radiologic improvements. It is a well-tolerated
      treatment modality for hemangiomas of the cavernous sinus.

PMID- 29037019
TI  - Effect of leukocyte alteration on treatment outcomes following preoperative
      chemoradiotherapy in patients with rectal cancer.
AB  - PURPOSE: Hematotoxicity following anti-cancer treatment is known to be related to
      treatment efficacy in several malignancies. The purpose of this study was to
      examine the hematologic parameters related to the tumor response and survival in
      patients treated with curative surgery following preoperative chemoradiotherapy
      (CRT) for rectal cancer. MATERIALS AND METHODS: Four hundred eighteen patients
      with rectal cancer who underwent preoperative CRT and curative surgery were
      analyzed, retrospectively. The main clinical factors and blood cell counts before
      and after CRT were investigated with respect to their relationships with tumor
      downstaging and patient survival. RESULTS: The post-CRT leukocyte count was
      significantly different between the tumor downstaging group and the
      nondownstaging group (median, 4740/uL vs. 5130/uL; p = 0.013). Multivariate
      analysis showed that histological grade, circumferential extent, and post-CRT
      leukocyte count were related to tumor downstaging. In addition, histological
      grade, post-CRT leukocyte count, and tumor downstaging were related to disease
      free survival. The 5-year disease-free survival and overall survival in patients
      with post-CRT leukocyte count <=3730/uL, which is the cut-off value derived from
      the receiver operation characteristic (ROC) curve analysis, were significantly
      higher than those with higher counts (88.0% vs. 71.6%, p = 0.001; 94.4% vs.
      84.1%, p = 0.024). CONCLUSION: Post-CRT leukocyte count of <=3730/uL could be
      regarded as a good prognostic factor for tumor response and survival in rectal
      cancer patients treated with preoperative CRT.

PMID- 29037020
TI  - Factors associated with pulmonary toxicity after myeloablative conditioning using
      fractionated total body irradiation.
AB  - PURPOSE: Pulmonary toxicities, including infectious pneumonia (IP) and idiopathic
      pneumonia syndrome (IPS), are serious side effects of total body irradiation
      (TBI) used for myeloablative conditioning. This study aimed to evaluate clinical
      factors associated with IP and IPS following TBI. MATERIALS AND METHODS: Fifty
      eight patients with hematologic malignancies who underwent TBI before allogeneic
      hematopoietic stem cell transplantation between 2005 and 2014 were reviewed. Most
      patients (91%) received 12 Gy in 1.5 Gy fractions twice a day. Pulmonary
      toxicities were diagnosed based on either radiographic evidence or reduced
      pulmonary function, and were subdivided into IP and IPS based on the presence or
      absence of concurrent infection. RESULTS: Pulmonary toxicities developed in 36
      patients (62%); 16 (28%) had IP and 20 (34%) had IPS. IP was significantly
      associated with increased treatment-related mortality (p = 0.028) and decreased
      survival (p = 0.039). Multivariate analysis revealed that the risk of developing
      IPS was significantly higher in patients who received stem cells from a matched
      unrelated donor than from a matched sibling donor (p = 0.021; hazard ratio [HR] =
      12.67; 95% confidence interval [CI], 1.46-110.30). Combining other conditioning
      agents with cyclophosphamide produced a higher tendency to develop IP (p = 0.064;
      HR = 6.19; 95% CI, 0.90-42.56). CONCLUSION: IP and IPS involve different risk
      factors and distinct pathogeneses that should be considered when planning
      treatments before and after TBI.

PMID- 29037021
TI  - Multimodal therapy for locally advanced prostate cancer: the roles of
      radiotherapy, androgen deprivation therapy, and their combination.
AB  - Locally advanced prostate cancer (LAPC) is defined as histologically proven T3-4
      prostatic adenocarcinoma. In this review, we define the individual roles of
      radiotherapy (RT), short-term (ST-) and long-term (LT-) androgen deprivation
      therapy (ADT), and their combination in multimodal therapy for LAPC. Despite
      limitations in comparing the clinical outcomes among published papers, in the
      present study, a trend of 10-year clinical outcomes was roughly estimated by
      calculating the average rates weighted by the cohort number. With RT alone, the
      following rates were estimated: 87% biochemical failure, 34% local failure (LF),
      48% distant metastasis (DM), 38% overall survival (OS), and 27% disease-specific
      mortality (DSM). Those associated with ADT alone were 74% BCF, 54% OS, and 25%
      DSM, which appeared to be better than those of RT alone. The addition of ADT to
      RT produced a notable local and systemic effect, regardless of ST- or LT-ADT. The
      LF rate decreased from 34% with RT alone to 21% with ST-ADT and further to 15%
      with LT-ADT. The DM and DSM rates also showed a similar trend among RT alone,
      RT+ST-ADT, and RT+LT-ADT. The combination of RT+LT-ADT resulted in the best long
      term clinical outcomes, indicating that both RT and ADT are important parts of
      multimodal therapy.

PMID- 29037022
TI  - Radiation recall dermatitis triggered by sorafenib after radiation therapy for
      hepatocellular carcinoma.
AB  - Sorafenib is widely used for unresectable and metastatic hepatocellular
      carcinomas. Radiation recall dermatitis (RRD) is an acute inflammatory reaction
      confined to previously irradiated skin that occurs after the administration of
      certain drugs. RRD after sorafenib treatment is rare; five cases have been
      reported thus far. We describe a 44-year-old man irradiated for chest wall bone
      metastasis from hepatocellular carcinoma. Eight days after radiotherapy
      completion, systemic therapy for metastatic hepatocellular carcinoma was
      initiated with sorafenib treatment. Eleven days after starting sorafenib, the
      patient complained of erythematous rash with pruritus in the chest wall, in a
      location consistent with the previous radiation field. Sorafenib was continued at
      the same dose, despite the RRD. The skin reaction subsided over the next 2 weeks
      without any medical intervention.

PMID- 29037023
TI  - Simultaneous integrated boost intensity-modulated radiotherapy versus 3
      dimensional conformal radiotherapy in preoperative concurrent chemoradiotherapy
      for locally advanced rectal cancer.
AB  - PURPOSE: To evaluate the feasibility of simultaneous integrated boost intensity
      modulated radiotherapy (SIB-IMRT) for preoperative concurrent chemoradiotherapy
      (PCRT) in locally advanced rectal cancer (LARC), by comparing with 3-dimensional
      conformal radiotherapy (3D-CRT). MATERIALS AND METHODS: Patients who were treated
      with PCRT for LARC from 2015 January to 2016 December were retrospectively
      enrolled. Total doses of 45 Gy to 50.4 Gy with 3D-CRT or SIB-IMRT were
      administered concomitantly with 5-fluorouracil plus leucovorin or capecitabine.
      Surgery was performed 8 weeks after PCRT. Between PCRT and surgery, one cycle of
      additional chemotherapy was administered. Pathologic tumor responses were
      compared between SIB-IMRT and 3D-CRT groups. Acute gastrointestinal,
      genitourinary, hematologic, and skin toxicities were compared between the two
      groups based on the RTOG toxicity criteria. RESULTS: SIB-IMRT was used in 53
      patients, and 3D-CRT in 41 patients. After PCRT, no significant differences were
      noted in tumor responses, pathologic complete response (9% vs. 7%; p = 1.000),
      pathologic tumor regression Grade 3 or higher (85% vs. 71%; p = 0.096), and R0
      resection (87% vs. 85%; p = 0.843). Grade 2 genitourinary toxicities were
      significantly lesser in the SIB-IMRT group (8% vs. 24%; p = 0.023), but
      gastrointestinal toxicities were not different across the two groups. CONCLUSION:
      SIB-IMRT showed lower GU toxicity and similar tumor responses when compared with
      3D-CRT in PCRT for LARC.

PMID- 29037024
TI  - Treatment outcome and risk analysis for cataract after radiotherapy of localized
      ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma.
AB  - PURPOSE: We retrospectively reviewed the results of radiotherapy for localized
      ocular adnexal MALT lymphoma (OAML) to investigate the risk factors of cataract.
      METHODS: Sixty-seven patients with stage IE OAML treated with radiotherapy at
      Seoul St. Mary's Hospital from 2001 to 2016 were included. Median treatment dose
      was 30 Gy. Lens protection was done in 52 (76%) patients. Radiation therapy (RT)
      extent was as follows: superficial (82.1%), tumor mass (4.5%), and entire orbital
      socket (13.4%). The risk factors for symptomatic cataract were analyzed using the
      Cox proportional hazard model. RESULTS: Median follow-up time was 50.9 months
      (range, 1.9 to 149.4 months). All patients were alive at the time of analysis.
      There were 7 recurrences and there was no local recurrence. Median time to
      recurrence was 40.4 months. There were 14 cases of symptomatic cataract. Dose >30
      Gy had hazard ratio of 3.47 for cataract (p = 0.026). Omitting lens protection
      showed hazard ratio of 4.10 (p = 0.008). CONCLUSIONS: RT achieves excellent local
      control of ocular MALT lymphoma. Consideration of RT-related factors such as lens
      protection and radiation dose at the stage of RT planning may reduce the risk of
      RT-induced cataract after radiotherapy.

PMID- 29037025
TI  - Gross tumor volume dependency on phase sorting methods of four-dimensional
      computed tomography images for lung cancer.
AB  - PURPOSE: To see the gross tumor volume (GTV) dependency according to the phase
      selection and reconstruction methods, we measured and analyzed the changes of
      tumor volume and motion at each phase in 20 cases with lung cancer patients who
      underwent image-guided radiotherapy. MATERIALS AND METHODS: We retrospectively
      analyzed four-dimensional computed tomography (4D-CT) images in 20 cases of 19
      patients who underwent image-guided radiotherapy. The 4D-CT images were
      reconstructed by the maximum intensity projection (MIP) and the minimum intensity
      projection (Min-IP) method after sorting phase as 40%-60%, 30%-70%, and 0%-90%.
      We analyzed the relationship between the range of motion and the change of GTV
      according to the reconstruction method. RESULTS: The motion ranges of GTVs are
      statistically significant only for the tumor motion in craniocaudal direction.
      The discrepancies of GTV volume and motion between MIP and Min-IP increased
      rapidly as the wider ranges of duty cycles are selected. CONCLUSION: As narrow as
      possible duty cycle such as 40%-60% and MIP reconstruction was suitable for lung
      cancer if the respiration was stable. Selecting the reconstruction methods and
      duty cycle is important for small size and for large motion range tumors.

PMID- 29037026
TI  - Treatment outcomes of extended-field radiation therapy for thoracic superficial
      esophageal cancer.
AB  - PURPOSE: To evaluate the efficacy and safety of extended-field radiation therapy
      for patients with thoracic superficial esophageal cancer (SEC). MATERIALS AND
      METHODS: From May 2007 to October 2016, a total of 24 patients with thoracic SEC
      (T1a and T1b) who underwent definitive radiotherapy and were analyzed
      retrospectively. The median total radiotherapy dose was 64 Gy (range, 54 to 66
      Gy) in conventional fractionation. All 24 patients received radiotherapy to whole
      thoracic esophagus and 23 patients received elective nodal irradiation. The
      supraclavicular lymph nodes, the celiac lymph nodes, and both of those nodal
      areas were included in 11, 3, and 9 patients, respectively. RESULTS: The median
      follow-up duration was 28.7 months (range 7.9 to 108.0 months). The 3-year
      overall survival, local control, and progression-free survival rates were 95.2%,
      89.7%, and 78.7%, respectively. There were 5 patients (20.8%) with progression of
      disease, 2 local failures (8.3%) and 3 (12.5%) regional failures. Three patients
      also experienced distant metastasis and had died of disease progression. There
      were no treatment-related toxicities of grade 3 or higher. CONCLUSION: Definitive
      extended-field radiotherapy for thoracic SEC showed durable disease control rates
      in medically inoperable and endoscopically unfit patients. Even extended-field
      radiotherapy with elective nodal irradiation was safe without grade 3 or 4
      toxicities.

PMID- 29037027
TI  - Refining prognostic stratification of human papillomavirus-related oropharyngeal
      squamous cell carcinoma: different prognosis between T1 and T2.
AB  - PURPOSE: To validate the 8th edition of the American Joint Committee on
      Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system for
      human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC)
      and investigate whether a modified classification better reflects the prognosis.
      MATERIALS AND METHODS: Medical records of patients diagnosed with non-metastatic
      HPV-related OPSCC between 2010 and 2016 at a single institution were
      retrospectively reviewed. HPV status was determined by immunohistochemical
      analysis of p16 and/or HPV DNA polymerase chain reaction (PCR). We reclassified
      TNM stage T0-1 and N0-1 as group A, T2-3 or N2 as B, and T4 or N3 as C. Survival
      analysis according to 8th AJCC/UICC TNM staging and the modified classification
      was performed. RESULTS: Of 383 OPSCC patients, 211 were positive for HPV DNA PCR
      or p16. After exclusion, 184 patients were included in this analysis. Median age
      was 56 years (range, 31 to 81 years). Most primary tumors were in the palatine
      tonsil (148 tumors, 80%). The eighth AJCC/UICC TNM classification could not
      differentiate between stage I and II (p = 0.470) or II and III (p = 0.209).
      Applying modified grouping, the 3-year overall survival rate of group A was
      significantly higher than that of group B and C (98% vs. 91%, p = 0.039 and 98%
      vs. 78%, p < 0.001, respectively). Differentiation between group B and C was
      marginally significant (p = 0.053). CONCLUSION: The 8th AJCC/UICC TNM staging
      system did not clearly distinguish the prognosis of stage II from that of other
      stages. Including the T2N0-1 group in stage II may improve prognostic
      stratification.

PMID- 29037028
TI  - Topological Self-Assembly of Highly Symmetric Lanthanide Clusters: A Magnetic
      Study of Exchange-Coupling "Fingerprints" in Giant Gadolinium(III) Cages.
AB  - The creation of a perfect hollow nanoscopic sphere of metal centers is clearly an
      unrealizable synthetic challenge. It is, however, an inspirational challenge from
      the viewpoint of chemical architecture and also as finite molecular species may
      provide unique microscopic insight into the origin and onset of phenomena such as
      topological spin-frustration effects found in infinite 2D and 3D systems. Herein,
      we report a series of high-symmetry gadolinium(III) (S = 7/2) polyhedra, Gd20,
      Gd32, Gd50, and Gd60, to test an approach based on assembling polymetallic
      fragments that contain different polygons. Structural analysis reveals that the
      Gd20 cage resembles a dodecahedron; the vertices of the Gd32 polyhedron exactly
      reveal symmetry Oh; Gd50 displays an unprecedented polyhedron in which an
      icosidodecahedron Gd30 core is encapsulated by an outer Gd20 dodecahedral shell
      with approximate Ih symmetry; and the Gd60 shows a truncated octahedron geometry.
      Experimental and theoretical magnetic studies show that this series produces the
      expected antiferromagnetic interaction that can be modeled based on classical
      spins at the Gd sites. From the magnetization analyses, we can roughly correlate
      the derivative bands to the Gd-O-Gd angles. Such a magneto-structural correlation
      may be used as "fingerprints" to identify these cages.

PMID- 29037029
TI  - Coupling N-H Deprotonation, C-H Activation, and Oxidation: Metal-Free C(sp3)-H
      Aminations with Unprotected Anilines.
AB  - An intramolecular oxidative C(sp3)-H amination from unprotected anilines and
      C(sp3)-H bonds readily occurs under mild conditions using t-BuOK, molecular
      oxygen and N,N-dimethylformamide (DMF). Success of this process, which requires
      mildly acidic N-H bonds and an activated C(sp3)-H bond (BDE < 85 kcal/mol), stems
      from synergy between basic, radical, and oxidizing species working together to
      promote a coordinated sequence of deprotonation: H atom transfer and oxidation
      that forges a new C-N bond. This process is applicable for the synthesis of a
      wide variety of N-heterocycles, ranging from small molecules to extended
      aromatics without the need for transition metals or strong oxidants.
      Computational results reveal the mechanistic details and energy landscape for the
      sequence of individual steps that comprise this reaction cascade. The importance
      of base in this process stems from the much greater acidity of transition state
      and product for the 2c,3e C-N bond formation relative to the reactant. In this
      scenario, selective deprotonation provides the driving force for the process.

PMID- 29037030
TI  - Semisynthetic Bioluminescent Sensor Proteins for Direct Detection of Antibodies
      and Small Molecules in Solution.
AB  - Single-step immunoassays that can be performed directly in solution are ideally
      suited for point-of-care diagnostics. Our group recently developed a new platform
      of bioluminescent sensor proteins (LUMABS; LUMinescent AntiBody Sensor) that
      allow antibody detection in blood plasma. Thus far, LUMABS has been limited to
      the detection of antibodies recognizing natural peptide epitopes. Here, we report
      the development of semisynthetic LUMABS sensors that recognize nonpeptide
      epitopes. The non-natural amino acid para-azidophenylalanine was introduced at
      the position of the original antibody-recognition sites as a chemical handle to
      enable site-specific conjugation of synthetic epitope molecules coupled to a
      dibenzocylcooctyne moiety via strain-promoted click chemistry. The approach was
      successfully demonstrated by developing semisynthetic LUMABS sensors for
      antibodies targeting the small molecules dinitrophenol and creatinine (DNP-LUMABS
      and CR-LUMABS) with affinities of 5.8 pM and 1.3 nM, respectively. An important
      application of these semisynthetic LUMABS is the detection of small molecules
      using a competitive assay format, which is demonstrated here for the detection of
      creatinine. Using a preassembled complex of CR-LUMABS and an anti-creatinine
      antibody, the detection of high micromolar concentrations of creatinine was
      possible both in buffer and in 1:1 diluted blood plasma. The use of semisynthetic
      LUMABS sensors significantly expands the range of antibody targets and enables
      the application of LUMABS sensors for the ratiometric bioluminescent detection of
      small molecules using a competitive immunoassay format.

PMID- 29037032
TI  - Substituent Effect on Intramolecular Charge Transfer of Symmetric Methoxy
      Substituted Bi-1,3,4-oxadiazole Derivatives.
AB  - Intramolecular charge-transfer characteristics of a series symmetric methoxy 
      substituted bi-1,3,4-oxadiazole derivatives with various substituted positions
      and quantities have been studied with a combination of experimental techniques
      and theoretical calculations to investigate the substituent effect. Different
      degrees of fluorescence red shift in polar solvents are observed in these
      compounds. The meta-substituted molecule (BOXD-m-OCH3) exhibits a larger red
      shift (82 nm) than the other two monosubstituted molecules, BOXD-o-OCH3 (40 nm)
      and BOXD-p-OCH3 (37 nm); the polysubstituted molecules BOXD-D1 and BOXD-T1 show
      80 and 104 nm red shifts, respectively, which are obviously larger than the
      monosubstituted molecules. The changes of molecular dipole moment between the
      ground state and charge transfer (CT) excited state are calculated to be on the
      same order with the degree of red shift (7.56 D in BOXD-o-OCH3, 12.07 D in BOXD-m
      OCH3, 7.38 D in BOXD-p-OCH3, 14.79 D in BOXD-D1, and 16.80 D in BOXD-T1).
      Theoretical calculations at the density functional theory level reveal that the
      first singlet excited state of all of these compounds shows both pi-pi* and CT
      characteristics and the charge has been proven to transfer from the terminal
      methoxy phenyl group to the central bioxadiazole group. The analysis of charge
      transfer based on electron density shows that the greater the amount substituent,
      the more charge would be involved in the intramolecular charge transfer. In
      addition, the negative barycenter has a tendency to locate close to the methoxy
      substituent, which would cause the difference in the charge-transferred distance.
      The transferred charge and CT distance work jointly and finally lead to
      differences in dipole moment variation. These findings could provide very good
      guidance for the design of molecules with intramolecular charge-transfer
      characteristics.

PMID- 29037033
TI  - Carboxymethylcellulose Mediates the Transport of Carbon Nanotube-Magnetite
      Nanohybrid Aggregates in Water-Saturated Porous Media.
AB  - Carbon-metal oxide nanohybrids (NHs) are increasingly recognized as the next
      generation, promising group of nanomaterials for solving emerging environmental
      issues and challenges. This research, for the first time, systematically explored
      the transport and retention of carbon nanotube-magnetite (CNT-Fe3O4) NH
      aggregates in water-saturated porous media under environmentally relevant
      conditions. A macromolecule modifier, carboxymethylcellulose (CMC), was employed
      to stabilize the NHs. Our results show that transport of the magnetic CNT-Fe3O4
      NHs was lower than that of nonmagnetic CNT due to larger hydrodynamic sizes of
      NHs (induced by magnetic attraction) and size-dependent retention in porous
      media. Classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory can explain the
      mobility of NHs under varying experimental conditions. However, in contrast with
      colloid filtration theory, a novel transport feature-an initial lower and a
      following sharp-higher peaks occurred frequently in the NHs' breakthrough curves.
      The magnitude and location of both transport peaks varied with different
      experimental conditions, due to the interplay between variability of fluid
      viscosity and size-selective retention of the NHs. Promisingly, the estimated
      maximum transport distance of NHs ranged between ~0.38 and 46 m, supporting the
      feasibility of employing the magnetically recyclable CNT-Fe3O4 NHs for in situ
      nanoremediation of contaminated soil, aquifer, and groundwater.

PMID- 29037031
TI  - Structural Mechanisms of Gating in Ionotropic Glutamate Receptors.
AB  - Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that
      mediate the majority of excitatory neurotransmission in the central nervous
      system. iGluRs open their ion channels in response to binding of the
      neurotransmitter glutamate, rapidly depolarize the postsynaptic neuronal
      membrane, and initiate signal transduction. Recent studies using X-ray
      crystallography and cryo-electron microscopy have determined full-length iGluR
      structures that (1) uncover the receptor architecture in an unliganded, resting
      state, (2) reveal conformational changes produced by ligands in order to activate
      iGluRs, open their ion channels, and conduct ions, and (3) show how activated,
      glutamate-bound iGluRs can adopt a nonconducting desensitized state. These new
      findings, combined with the results of previous structural and functional
      experiments, kinetic and molecular modeling, mutagenesis, and biochemical
      analyses, provide new views on the structural mechanisms of iGluR gating.

PMID- 29037034
TI  - Pairwise H2/D2 Exchange and H2 Substitution at a Bimetallic Dinickel(II) Complex
      Featuring Two Terminal Hydrides.
AB  - A compartmental ligand scaffold HL with two beta-diketiminato binding sites
      spanned by a pyrazolate bridge gave a series of dinuclear nickel(II) dihydride
      complexes M[LNi2(H)2], M = Na (Na.2) and K (K.2), which were isolated after
      reacting the precursor complex [LNi2(MU-Br)] (1) with MHBEt3 (M = Na and K).
      Crystallographic characterization showed the two hydride ligands to be directed
      into the bimetallic pocket, closely interacting with the alkali metal cation.
      Treatment of K.2 with dibenzo(18-crown-6) led to the separated ion pair
      [LNi2(H)2][K(DB18C6)] (2[K(DB18C6)]). Reaction of Na.2 or K.2 with D2 was
      investigated by a suite of 1H and 2H NMR experiments, revealing an unusual
      pairwise H2/D2 exchange process that synchronously involves both Ni-H moieties
      without H/D scrambling. A mechanistic picture was provided by DFT calculations
      which suggested facile recombination of the two terminal hydrides within the
      bimetallic cleft, with a moderate enthalpic barrier of ~62 kJ/mol, to give H2 and
      an antiferromagnetically coupled [LNiI2]- species. This was confirmed by SQUID
      monitoring during H2 release from solid 2[K(DB18C6)]. Interaction with the Lewis
      acid cation (Na+ or K+) significantly stabilizes the dihydride core. Kinetic data
      for the M[L(Ni-H)2] -> H2 transition derived from 2D 1H EXSY spectra confirmed
      first-order dependence of H2 release on M.2 concentration and a strong effect of
      the alkali metal cation M+. Treating [LNi2(D)2]- with phenylacetylene led to D2
      and dinickel(II) complex 3- with a twice reduced styrene-1,2-diyl bridging unit
      in the bimetallic pocket. Complexes [LNiII2(H)2]- having two adjacent terminal
      hydrides thus represent a masked version of a highly reactive dinickel(I) core.
      Storing two reducing equivalents in adjacent metal hydrides that evolve H2 upon
      substrate binding is reminiscent of the proposed N2 binding step at the FeMo
      cofactor of nitrogenase, suggesting the use of the present bimetallic scaffold
      for reductive bioinspired activation of a range of inert small molecules.

PMID- 29037035
TI  - Computational Prediction of Excited-State Carbon Tunneling in the Two Steps of
      Triplet Zimmerman Di-pi-Methane Rearrangement.
AB  - The photoinduced Zimmerman di-pi-methane (DPM) rearrangement of polycyclic
      molecules to form synthetically useful cyclopropane derivatives was found
      experimentally to proceed in a triplet excited state. We have applied state-of
      the-art quantum mechanical methods, including M06-2X, DLPNO-CCSD(T) and
      variational transition-state theory with multidimensional tunneling corrections,
      to an investigation of the reaction rates of the two steps in the triplet DPM
      rearrangement of dibenzobarrelene, benzobarrelene and barrelene. This study
      predicts a high probability of carbon tunneling in regions around the two
      consecutive transition states at 200-300 K, and an enhancement in the rates by
      104-276/35-67% with carbon tunneling at 200/300 K. The Arrhenius plots of the
      rate constants were found to be curved at low temperatures. Moreover, the
      computed 12C/13C kinetic isotope effects were affected significantly by carbon
      tunneling and temperature. Our predictions of electronically excited-state carbon
      tunneling and two consecutive carbon tunneling are unprecedented. Heavy-atom
      tunneling in some photoinduced reactions with reactive intermediates and narrow
      barriers can be potentially observed at relatively low temperature in
      experiments.

PMID- 29037037
TI  - Superlow Friction of Graphite Induced by the Self-Assembly of Sodium Dodecyl
      Sulfate Molecular Layers.
AB  - Two-dimensional (2D) layered materials usually exhibit superlow friction
      properties when the shear occurs between incommensurate interface lattices. In
      this work, we propose a new method, which is different from the traditional
      structure superlubricity, to achieve the superlow friction of graphite. This
      method involves attaching sodium dodecyl sulfate (SDS) molecular layers on the
      friction surfaces by self-assembly and sliding across the aqueous medium. The
      friction coefficient between graphite and silica can be reduced to approximately
      0.005 at a maximal contact pressure of 31 MPa by this method. The mechanism of
      the superlow friction was investigated by using an atomic force microscopy and
      can be attributed to the extremely weak interaction between graphite and SDS
      molecules. It forms a shear plane of SDS molecules/graphite with extremely low
      shear strength and extremely low adhesion. This finding provides new insights
      into the molecular mechanisms underlying an efficient lubrication of 2D layered
      materials in liquid.

PMID- 29037036
TI  - Intramolecular London Dispersion Interaction Effects on Gas-Phase and Solid-State
      Structures of Diamondoid Dimers.
AB  - The covalent diamantyl (C28H38) and oxadiamantyl (C26H34O2) dimers are stabilized
      by London dispersion attractions between the dimer moieties. Their solid-state
      and gas-phase structures were studied using a multitechnique approach, including
      single-crystal X-ray diffraction (XRD), gas-phase electron diffraction (GED), a
      combined GED/microwave (MW) spectroscopy study, and quantum chemical
      calculations. The inclusion of medium-range electron correlation as well as the
      London dispersion energy in density functional theory is essential to reproduce
      the experimental geometries. The conformational dynamics computed for C26H34O2
      agree well with solution NMR data and help in the assignment of the gas-phase MW
      data to individual diastereomers. Both in the solid state and the gas phase the
      central C-C bond is of similar length for the diamantyl [XRD, 1.642(2) A; GED,
      1.630(5) A] and the oxadiamantyl dimers [XRD, 1.643(1) A; GED, 1.632(9) A;
      GED+MW, 1.632(5) A], despite the presence of two oxygen atoms. Out of a larger
      series of quantum chemical computations, the best match with the experimental
      reference data is achieved with the PBEh-3c, PBE0-D3, PBE0, B3PW91-D3, and M06-2X
      approaches. This is the first gas-phase confirmation that the markedly elongated
      C-C bond is an intrinsic feature of the molecule and that crystal packing effects
      have only a minor influence.

PMID- 29037040
TI  - Highly Flexible and Sensitive Wearable E-Skin Based on Graphite Nanoplatelet and
      Polyurethane Nanocomposite Films in Mass Industry Production Available.
AB  - Graphene and nanomaterials based flexible pressure sensors R&D activities are
      becoming hot topics due to the huge marketing demand on wearable devices and
      electronic skin (E-Skin) to monitor the human body's actions for dedicated
      healthcare. Herein, we report a facile and efficient fabrication strategy to
      construct a new type of highly flexible and sensitive wearable E-Skin based on
      graphite nanoplates (GNP) and polyurethane (PU) nanocomposite films. The
      developed GNP/PU E-Skin sensors are highly flexible with good electrical
      conductivity due to their unique binary microstructures with synergistic
      interfacial characteristics, which are sensitive to both static and dynamic
      pressure variation, and can even accurately and quickly detect the pressure as
      low as 0.005 N/50 Pa and momentum as low as 1.9 mN.s with a gauge factor of 0.9
      at the strain variation of up to 30%. Importantly, our GNP/PU E-Skin is also
      highly sensitive to finger bending and stretching with a linear correlation
      between the relative resistance change and the corresponding bending angles or
      elongation percentage. In addition, our E-Skin shows excellent sensitivity to
      voice vibration when exposed to a volunteer's voice vibration testing. Notably,
      the entire E-Skin fabrication process is scalable, low cost, and industrially
      available. Our complementary experiments with comprehensive results demonstrate
      that the developed GNP/PU E-Skin is impressively promising for practical
      healthcare applications in wearable devices, and enables us to monitor the real
      world force signals in real-time and in-situ mode from pressing, hitting,
      bending, stretching, and voice vibration.

PMID- 29037039
TI  - Synthesis and Preclinical Evaluation of 18F-PEG3-FPN for the Detection of
      Metastatic Pigmented Melanoma.
AB  - Although 18F-5-fluoro-N-(2-[diethylamino]ethyl)picolinamide (18F-5-FPN) is
      considered a promising radiopharmaceutical for PET imaging of melanoma, it
      accumulates at high concentrations in the liver. The aim in this research was to
      optimize the structure of 18F-5-FPN with triethylene glycol to reduce liver
      uptake as well as improve pharmacokinetics, and to evaluate its performance in
      detection of melanoma liver and lung metastases. 18F-PEG3-FPN was successfully
      prepared with a high radiolabeling yield (44.68% +/- 5.99%) and radiochemical
      purity (>99%). The uptake of 18F-PEG3-FPN by pigmented B16F10 melanoma cells was
      significantly higher than that by amelanotic melanoma A375 cells. The binding to
      B16F10 cells could be blocked by excess 19F-PEG3-FPN. On small animal PET images,
      B16F10 tumors, but not A375 tumors, were clearly delineated after 18F-PEG3-FPN
      injection. More importantly, 18F-PEG3-FPN uptake by liver (2.27 +/- 0.45 and 1.74
      +/- 0.35% ID/g, at 1 and 2 h) was significantly lower than that of 18F-5-FPN, and
      the lesions in lung and liver could be clearly detected by 18F-PEG3-FPN PET
      imaging in mouse models of pulmonary or hepatic metastases. Overall, we
      successfully synthesized 18F-PEG3-FPN, which has higher labeling efficacy and
      better in vivo pharmacokinetics along with lower liver uptake compared to 18F-5
      FPN. This suggests 18F-PEG3-FPN as a candidate for pigmented melanoma liver and
      lung metastasis detection.

PMID- 29037038
TI  - Conformationally Dynamic Radical Transfer within Ribonucleotide Reductase.
AB  - Ribonucleotide reductases (RNR) catalyze the reduction of nucleotides to
      deoxynucleotides through a mechanism involving an essential cysteine based thiyl
      radical. In the E. coli class 1a RNR the thiyl radical (C439*) is a transient
      species generated by radical transfer (RT) from a stable diferric-tyrosyl radical
      cofactor located >35 A away across the alpha2:beta2 subunit interface. RT is
      facilitated by sequential proton-coupled electron transfer (PCET) steps along a
      pathway of redox active amino acids (Y122beta <-> [W48beta?] <-> Y356beta <->
      Y731alpha <-> Y730alpha <-> C439alpha). The mutant R411A(alpha) disrupts the H
      bonding environment and conformation of Y731, ostensibly breaking the RT pathway
      in alpha2. However, the R411A protein retains significant enzymatic activity,
      suggesting Y731 is conformationally dynamic on the time scale of turnover.
      Installation of the radical trap 3-amino tyrosine (NH2Y) by amber codon
      suppression at positions Y731 or Y730 and investigation of the NH2Y* trapped
      state in the active alpha2:beta2 complex by HYSCORE spectroscopy validate that
      the perturbed conformation of Y731 in R411A-alpha2 is dynamic, reforming the H
      bond between Y731 and Y730 to allow RT to propagate to Y730. Kinetic studies
      facilitated by photochemical radical generation reveal that Y731 changes
      conformation on the ns-MUs time scale, significantly faster than the enzymatic
      kcat. Furthermore, the kinetics of RT across the subunit interface were directly
      assessed for the first time, demonstrating conformationally dependent RT rates
      that increase from 0.6 to 1.6 * 104 s-1 when comparing wild type to R411A-alpha2,
      respectively. These results illustrate the role of conformational flexibility in
      modulating RT kinetics by targeting the PCET pathway of radical transport.

PMID- 29037041
TI  - Triazenyl Radicals Stabilized by N-Heterocyclic Carbenes.
AB  - Notwithstanding the notable progress in the synthesis of N-heterocyclic carbene
      stabilized radicals, aminyl radicals, supported by NHCs or otherwise, have been
      scarcely studied due to synthetic challenges. Triazenyl radical is a particular
      form of aminyl radical that contains three adjacent nitrogen atoms, and offers
      intriguing possibilities for unique reactivity and physical properties stemming
      from expected delocalization of the spin density over the NNN moiety and its
      conjugated substituents. Here, we report the synthesis and full characterization
      of the first NHC-stabilized triazenyl radicals, obtained by one-electron
      reduction of the corresponding triazenyl cations with potassium metal. These
      radicals reversibly oxidize back to the cations upon treatment with transition
      metal sources or electrophiles, and abstract H atom from xanthene to form a new N
      H bond at the center nitrogen atom. Potential application of the redox couple
      between triazenyl cation and triazenyl radical was demonstrated as cathode active
      materials in lithium ion batteries.

PMID- 29037042
TI  - Structural Monitoring of the Onset of Excited-State Aromaticity in a Liquid
      Crystal Phase.
AB  - Aromaticity of photoexcited molecules is an important concept in organic
      chemistry. Its theory, Baird's rule for triplet aromaticity since 1972 gives the
      rationale of photoinduced conformational changes and photochemical reactivities
      of cyclic pi-conjugated systems. However, it is still challenging to monitor the
      dynamic structural change induced by the excited-state aromaticity, particularly
      in condensed materials. Here we report direct structural observation of a
      molecular motion and a subsequent packing deformation accompanied by the excited
      state aromaticity. Photoactive liquid crystal (LC) molecules featuring a pi
      expanded cyclooctatetraene core unit are orientationally ordered but loosely
      packed in a columnar LC phase, and therefore a photoinduced conformational
      planarization by the excited-state aromaticity has been successfully observed by
      time-resolved electron diffractometry and vibrational spectroscopy. The
      structural change took place in the vicinity of excited molecules, producing a
      twisted stacking structure. A nanoscale torque driven by the excited-state
      aromaticity can be used as the working mechanism of new photoresponsive
      materials.

PMID- 29037043
TI  - Thermally Induced Encapsulation of Food Nutrients into Phytoferritin through the
      Flexible Channels without Additives.
AB  - The cavity of phytoferritin provides a nanospace to encapsulate and deliver food
      nutrient molecules. However, tranditional methods to prepare the ferritin
      nutrient complexes must undergo acid/alkaline conditions or apply additives. In
      this work, we provide a novel guideline that thermal treatment at 60  degrees C
      can expand ferritin channels by uncoiling the surrounding alpha-helix. Upon
      reduction of the temperature to 20  degrees C, food nutrient rutin can be
      encapsulated in apo-soybean seed ferritin (apoSSF) at pH 7.0 through channels
      without disassembly of the protein cage and with no addition of additives.
      Results indicated that one apoSSF could encapsulate about 10.5 molecules of
      rutin, with an encapsulation ratio of 8.08% (w/w). In addition, the resulting
      rutin-loaded SSF complexes were monodispersed in a size of 12 nm in aqueous
      solution. This work provides a novel pathway for the encapsulation of food
      nutrient molecules into the nanocavity of ferritin under a neutral pH condition
      induced by thermal treatment.

PMID- 29037044
TI  - Porous Poly(epsilon-caprolactone)-Poly(l-lactic acid) Semi-Interpenetrating
      Networks as Superior, Defect-Specific Scaffolds with Potential for Cranial Bone
      Defect Repair.
AB  - The treatment of irregular cranial bone defects is currently limited due to the
      graft resorption that can occur when an ill-fitting interface exists between an
      autograft and the surrounding tissue. A tissue engineering scaffold able to
      achieve defect-specific geometries could improve healing. This work reports a
      macroporous, shape memory polymer (SMP) scaffold composed of a semi
      interpenetrating network (semi-IPN) of thermoplastic poly(l-lactic acid) (PLLA)
      within cross-linked poly(epsilon-caprolactone) diacrylate (PCL-DA) that is
      capable of conformal fit within a defect. The macroporous scaffolds were
      fabricated using a fused salt template and were also found to have superior,
      highly controlled properties needed for regeneration. Specifically, the scaffolds
      displayed interconnected pores, improved rigidity, and controlled, accelerated
      degradation. Although slow degradation rates of scaffolds can limit healing, the
      unique degradation behavior observed could prove promising. Thus, the described
      SMP semi-IPN scaffolds overcome two of the largest limitations in bone tissue
      engineering: defect "fit" and tailored degradation.

PMID- 29037045
TI  - Bi4O4Cu1.7Se2.7Cl0.3: Intergrowth of BiOCuSe and Bi2O2Se Stabilized by the
      Addition of a Third Anion.
AB  - Layered two-anion compounds are of interest for their diverse electronic
      properties. The modular nature of their layered structures offers opportunities
      for the construction of complex stackings used to introduce or tune
      functionality, but the accessible layer combinations are limited by the crystal
      chemistries of the available anions. We present a layered three-anion material,
      Bi4O4Cu1.7Se2.7Cl0.3, which adopts a new structure type composed of alternately
      stacked BiOCuSe and Bi2O2Se-like units. This structure is accessed by inclusion
      of three chemically distinct anions, which are accommodated by aliovalently
      substituted Bi2O2Se0.7Cl0.3 blocks coupled to Cu-deficient Bi2O2Cu1.7Se2 blocks,
      producing a formal charge modulation along the stacking direction. The
      hypothetical parent phase Bi4O4Cu2Se3 is unstable with respect to its charge
      neutral stoichiometric building blocks. The complex layer stacking confers
      excellent thermal properties upon Bi4O4Cu1.7Se2.7Cl0.3: a room-temperature
      thermal conductivity (kappa) of 0.4(1) W/mK was measured on a pellet with
      preferred crystallite orientation along the stacking axis, with perpendicular
      measurement indicating it is also highly anisotropic. This kappa value lies in
      the ultralow regime and is smaller than those of both BiOCuSe and Bi2O2Se.
      Bi4O4Cu1.7Se2.7Cl0.3 behaves like a charge-balanced semiconductor with a narrow
      band gap. The chemical diversity offered by the additional anion allows the
      integration of two common structural units in a single phase by the simultaneous
      and coupled creation of charge-balancing defects in each of the units.

PMID- 29037046
TI  - ADMET Evaluation in Drug Discovery. 18. Reliable Prediction of Chemical-Induced
      Urinary Tract Toxicity by Boosting Machine Learning Approaches.
AB  - Xenobiotic chemicals and their metabolites are mainly excreted out of our bodies
      by the urinary tract through the urine. Chemical-induced urinary tract toxicity
      is one of the main reasons that cause failure during drug development, and it is
      a common adverse event for medications, natural supplements, and environmental
      chemicals. Despite its importance, there are only a few in silico models for
      assessing urinary tract toxicity for a large number of compounds with diverse
      chemical structures. Here, we developed a series of qualitative and quantitative
      structure-activity relationship (QSAR) models for predicting urinary tract
      toxicity. In our study, the recursive feature elimination method incorporated
      with random forests (RFE-RF) was used for dimension reduction, and then eight
      machine learning approaches were used for QSAR modeling, i.e., relevance vector
      machine (RVM), support vector machine (SVM), regularized random forest (RRF),
      C5.0 trees, eXtreme gradient boosting (XGBoost), AdaBoost.M1, SVM boosting
      (SVMBoost), and RVM boosting (RVMBoost). For building classification models, the
      synthetic minority oversampling technique was used to handle the imbalance data
      set problem. Among all the machine learning approaches, SVMBoost based on the RBF
      kernel achieves both the best quantitative (qext2 = 0.845) and qualitative
      predictions for the test set (MCC of 0.787, AUC of 0.893, sensitivity of 89.6%,
      specificity of 94.1%, and global accuracy of 90.8%). The application domains were
      then analyzed, and all of the tested chemicals fall within the application domain
      coverage. We also examined the structure features of the chemicals with large
      prediction errors. In brief, both the regression and classification models
      developed by the SVMBoost approach have reliable prediction capability for
      assessing chemical-induced urinary tract toxicity.

PMID- 29037047
TI  - Peptides on the Rise.

PMID- 29037048
TI  - New Discoveries to Old Problems: A Virtual Issue on Air Pollution in Rapidly
      Industrializing Countries.

PMID- 29037050
TI  - Simian Immunodeficiency Virus Infection Increases Blood Ethanol Concentration
      Duration After Both Acute and Chronic Administration.
AB  - Alcohol use disorder (AUD) is a frequent comorbidity among people living with
      HIV/AIDS (PLWHA). Alcohol consumption is a significant predictor of nonadherence
      to antiretroviral therapy (ART), as well as worsening immunological and
      virological indicators among PLWHA. Clinical studies indicate that higher viral
      loads increase sensitivity to alcohol in PLWHA. The factors that influence
      alcohol kinetics after HIV infection and initiation of ART are not well
      understood, limiting the information upon which interventions can be designed to
      ameliorate the impact of alcohol misuse on this vulnerable patient population. To
      better understand the relationship between viral load and alcohol kinetics, we
      measured changes in doses of intragastric ethanol administration to achieve
      target blood ethanol concentration (BEC) in a rhesus macaque model of chronic
      binge alcohol (CBA) administration and acute changes following a single acute
      binge dose of alcohol (ABA) pre- and post-simian immunodeficiency virus (SIV)
      infection, and following ART initiation. Our results from CBA (14 months)
      administered SIV-infected male macaques showed that, following ART initiation,
      macaques required higher doses of alcohol to achieve a target peak BEC compared
      with non-ART-treated SIV-infected macaques. In animals given ABA, we found
      prolonged duration of elevated BEC and decreased elimination rate of alcohol that
      was not corrected following 7 weeks of ART. These findings suggest that binge
      drinking associated with AUD could negatively interact with HIV infection and
      enhance disease progression. These findings further support the need for
      implementation of behavioral or therapeutic interventions to decrease alcohol
      consumption to improve the quality of life in PLWHA.

PMID- 29037051
TI  - T Regulatory Cell Induced Foxp3 Binds the IL2, IFNgamma, and TNFalpha Promoters
      in Virus-Specific CD8+ T Cells from Feline Immunodeficiency Virus Infected Cats.
AB  - Polyfunctional CD8+ T cells play a critical role in controlling viremia during
      AIDS lentiviral infections. However, for most HIV-infected individuals, virus
      specific CD8+ T cells exhibit loss of polyfunctionality, including loss of IL2,
      TNFalpha, and IFNgamma. Using the feline immunodeficiency virus (FIV) model for
      AIDS lentiviral persistence, our laboratory has demonstrated that FIV-activated
      Treg cells target CD8+ T cells, leading to a reduction in IL2 and IFNgamma
      production. Furthermore, we have demonstrated that Treg cells induce expression
      of the repressive transcription factor, Foxp3, in CD8+ T cells. Based upon these
      findings, we asked if Treg-induced Foxp3 could bind to the IL2, TNFalpha, and
      IFNgamma promoter regions in virus-specific CD8+ T cells. Following coculture
      with autologous Treg cells, we demonstrated decreased mRNA levels of IL2 and
      IFNgamma at weeks 4 and 8 postinfection and decreased TNFalpha at week 4
      postinfection in virus-specific CD8+ T cells. We also clearly demonstrated Treg
      cell-induced Foxp3 expression in virus-specific CD8+ T cells at weeks 1, 4, and 8
      postinfection. Finally, we documented Foxp3 binding to the IL2, TNFalpha, and
      IFNgamma promoters at 8 weeks and 6 months postinfection in virus-specific CD8+ T
      cells following Treg cell coculture. In summary, the results here clearly
      demonstrate that Foxp3 inhibits IL2, TNFalpha, and IFNgamma transcription by
      binding to their promoter regions in lentivirus-specific CD8+ T cells. We believe
      this is the first description of this process during the course of AIDS
      lentiviral infection.

PMID- 29037049
TI  - Detection and Characterization of Reactive Oxygen and Nitrogen Species in
      Biological Systems by Monitoring Species-Specific Products.
AB  - SIGNIFICANCE: Since the discovery of the superoxide dismutase enzyme, the
      generation and fate of short-lived oxidizing, nitrosating, nitrating, and
      halogenating species in biological systems has been of great interest. Despite
      the significance of reactive oxygen species (ROS) and reactive nitrogen species
      (RNS) in numerous diseases and intracellular signaling, the rigorous detection of
      ROS and RNS has remained a challenge. Recent Advances: Chemical characterization
      of the reactions of selected ROS and RNS with electron paramagnetic resonance
      (EPR) spin traps and fluorescent probes led to the establishment of species
      specific products, which can be used for specific detection of several forms of
      ROS and RNS in cell-free systems and in cultured cells in vitro and in animals in
      vivo. Profiling oxidation products from the ROS and RNS probes provides a
      rigorous method for detection of those species in biological systems. CRITICAL
      ISSUES: Formation and detection of species-specific products from the probes
      enables accurate characterization of the oxidative environment in cells.
      Measurement of the total signal (fluorescence, chemiluminescence, etc.) intensity
      does not allow for identification of the ROS/RNS formed. It is critical to
      identify the products formed by using chromatographic or other rigorous
      techniques. Product analyses should be accompanied by monitoring of the
      intracellular probe level, another factor controlling the yield of the product(s)
      formed. FUTURE DIRECTIONS: More work is required to characterize the chemical
      reactivity of the ROS/RNS probes, and to develop new probes/detection approaches
      enabling real-time, selective monitoring of the specific products formed from the
      probes. Antioxid. Redox Signal. 28, 1416-1432.

PMID- 29037053
TI  - Microorganisms as an Indicator of Hygiene Status Among Migrant Food Handlers in
      Peninsular Malaysia.
AB  - This study used microbial indicators to assess the hygiene status of 383 migrant
      food handlers from 3 urban cities in Peninsular Malaysia. Microbiological
      analysis revealed that all the hand swabs tested 99.5% positive for aerobic plate
      counts (mean [M] +/- standard deviation [SD] = 3.57 +/- 0.83 log10CFU [colony
      forming unit]), 20.8% positive for total coliform/ Escherichia coli (M +/- SD =
      0.30 +/- 0.67 log10CFU), and 63.4% positive for Staphylococcus aureus (M +/- SD =
      1.38 +/- 1.26 log10CFU). In addition, aerobic plate counts and Staphylococcus
      aureus counts exceeded the acceptable standard levels. Bacterial counts were
      found to be significantly associated with subjects' country of origin ( P = .019)
      and working responsibilities ( P = .001). Our findings indicate high probability
      of transmission of pathogenic bacteria from the food handlers' hands to customers
      during meal preparation and serving. This calls for improvements in personal
      hygiene and sanitation standards by the relevant health authorities among migrant
      food handlers.

PMID- 29037055
TI  - Computer aided diagnosis sensor integrated outdoor shirts for real time heart
      disease monitoring.
AB  - The typical method of monitoring arrhythmia is to use a body patch type sensor
      with a wet electrode. It has several problems caused by wet electrodes for long
      term monitoring. Thus, a monitoring sensor integrated into clothes with a dry
      electrode is proposed. In this study, we develop a smart outdoor shirt equipped
      with a dry electrode electrocardiogram (ECG) sensor for a cardiac arrhythmia
      computer aided diagnosis system. The sensor can be inserted in a console close to
      the chest, charged, used to communicate wirelessly, and connected with a
      smartphone application. The ECG signals measured by the smart shirt indicated
      that 97.5 +/- 1% of the signals could be measured in an immobile state and at
      least 85.2 +/- 2% of the signals could be measured during movement. We propose a
      computer aided diagnosis system for detecting cardiac arrhythmia. It was
      determined through experiments that the system can detect arrhythmia with an
      accuracy of 98.2 +/- 2%. This study suggests that smart shirt which can diagnose
      arrhythmia will provide information that can quickly recognize arrhythmia in
      daily life or exercise.

PMID- 29037054
TI  - Exposure to Tobacco Advertising, Promotion Among the Adult Population in Vietnam
      and Its Implications for Public Health.
AB  - INTRODUCTION: The Law on Tobacco Control and the Law on Advertisement prohibit
      the advertising of any tobacco product in Vietnam. Tobacco promotion and
      marketing are alsostrictly prohibited. However, the violation of tobacco
      adverting and promotion is still common in Vietnam. OBJECTIVES: This article aims
      at describing the exposure to tobacco advertising and promotion among the
      population aged 15+ years in Vietnam based on the data from the Global Adult
      Tobacco Survey 2015 from the view of the community, identifying any possible
      associations between the exposure to tobacco advertising and promotion and other
      individual factors, and discussing its possible public health implications.
      METHOD: A cross-sectional study with the nationwide scale. Secondary data from
      the Global Adult Tobacco Survey 2015 was explored and analyzed. Chi-square test
      and multivariate logistic regressions were applied in the data analysis. RESULTS:
      The most common type of adults' exposure to tobacco advertising and promotion was
      points of sale (8.6%); 9.8% adults exposure to one source of tobacco advertising
      and 4.0% of them exposed to one source of tobacco promotion. Around 13.3% of
      Vietnamese adults were exposed to tobacco advertisement, while 2.0% were exposed
      to tobacco promotion, 5.3% were exposed to both tobacco advertising and
      promotion, and 16.6% were exposed to tobacco advertising or promotion. Gender,
      educational level, age, occupation, marital status, socioeconomic status,
      location (urban, rural), and current smoking status were associated with the
      exposure to tobacco advertising, tobacco promotion, tobacco advertising and
      promotion, and tobacco advertising or promotion. CONCLUSION AND RECOMMENDATION:
      Although there are comprehensive bans on tobacco advertising and promotion in
      Vietnam, adults aged 15+ years still reported their exposure to tobacco
      advertising and promotion. There should be a strict enforcement of the ban on
      tobacco advertising and promotion in Vietnam.

PMID- 29037056
TI  - [Neuroacanthocytosis diagnosis with new generation whole exome sequencing].
AB  - In a patient with marked symptoms of Huntington disease after the huntingtin
      testing, which gave normal result, a whole exome sequencing (WES) has been
      performed based on an international collaboration. A homozygous G>A nucleotid
      change in the exon 34 of the VPS13A gene has been detected with WES, a mutation
      resulting in a premature stop codon at the position 1301. This change is a known
      pathogenic mutation. The aim of this article is to draw attention on the
      importance of the WES in the diagnosis of rare neurological diseases without any
      specific symptoms. Orv Hetil. 2017; 158(42): 1681-1684.

PMID- 29037057
TI  - [One year adherence of ramipril versus ramipril/amlodipine fixed dose combination
      therapy in hypertension].
AB  - INTRODUCTION: In the treatment of hypertension avoiding adverse cardiovascular
      complications to achieve target blood pressure is essential. The appropriate drug
      selection, and if necessary to change to combination therapy, patients adherence
      is important which may help fixed dose combination. AIM: The aim of the authors
      was to investigate the one year adherence of the ramipril and ramipril/amlodipine
      fixed dose combination in hypertensive patients. METHOD: Prescriptions database
      of the National Health Insurance Fund in Hungary on pharmacy-claims was analysed
      between October 1, 2012 and September 30, 2013. The authors identified patients
      who filled prescriptions for ramipril monotherapy and fixed dose combinations of
      ramipril/amlodipine prescribed for the first time in hypertensive patients who
      have not received similar drugs in the previous year. To model the adherence, the
      apparatus of survival analysis was used, where "survival" was the time to abandon
      the medication. As it was available to month precision, discrete time survival
      analysis was applied: a generalized linear model was estimated with complementary
      log-log link function with the kind of drug being the only explanatory variable.
      RESULTS: 92,546 patients met the inclusion criteria. During the trial period,
      ramipril therapy or ramipril/amlodipine fixed dose combination was started in
      82,251 and 10,295 patients, respectively. One year persistence rate in patients
      with ramipril was 30% and 54% in patients with ramipril/amlodipine fixed dose
      combination therapy. Considering only the 360-day study period, the mean duration
      of persistence was 189.9 days in patients on ramipril and 270.6 days on
      ramipril/amlodipine fixed dose combination therapy. The hazard of discontinuation
      was more than twofold higher during treatment with ramipril compared with the use
      of the ramipril/amlodipine fixed dose combination therapy (HR = 2.11 [95% CI:
      2.05-2.17], p<0,001). CONCLUSIONS: There is a significant difference between the
      one year persistence of ramipril and ramipril/amlodipine fixed dose combination
      therapy in hypertension. The result demonstrated that ramipril/amlodipine fixed
      dose combination therapy has a better one year persistence rate. When the next
      step is necessary to achieve target blood pressure, ramipril/amlodipine fixed
      dose combination therapy is preferable. Orv Hetil. 2017; 158(42): 1668-1673.

PMID- 29037052
TI  - Redox-Sensitive Innate Immune Pathways During Macrophage Activation in Type 1
      Diabetes.
AB  - SIGNIFICANCE: Type 1 diabetes (T1D) is an autoimmune disease resulting in beta
      cell destruction mediated by islet-infiltrating leukocytes. The role of oxidative
      stress in human and murine models of T1D is highly significant as these noxious
      molecules contribute to diabetic complications and beta-cell lysis, but their
      direct impact on dysregulated autoimmune responses is highly understudied. Pro
      inflammatory macrophages play a vital role in the initiation and effector phases
      of T1D by producing free radicals and pro-inflammatory cytokines to facilitate
      beta-cell destruction and to present antigen to autoreactive T cells. Recent
      Advances: Redox modulation of macrophage functions may play critical roles in
      autoimmunity. These include enhancing pro-inflammatory innate immune signaling
      pathways in response to environmental triggers, enforcing an M1 macrophage
      differentiation program, controlling antigen processing, and altering peptide
      recognition by oxidative post-translational modification. Therefore, an oxidative
      environment may act on multiple macrophage functions to orchestrate T1D
      pathogenesis. CRITICAL ISSUES: Mechanisms involved in the initiation of T1D
      remain unclear, making preventive and early therapeutics difficult to develop.
      Although many of these advances in the redox regulation of macrophages are in
      their infancy, they provide insight into how oxidative stress aids in the
      precipitating event of autoimmune activation. FUTURE DIRECTIONS: Future studies
      should be aimed at mechanistically determining which redox-regulated macrophage
      functions are pertinent in T1D pathogenesis, as well as at investigating
      potential targetable therapeutics to halt and/or dampen innate immune activation
      in T1D.

PMID- 29037058
TI  - [Efficacy of the population-based pilot colorectal screening program. Hungary,
      Csongrad county, 2015].
AB  - INTRODUCTION: In Hungary, a nationwide colorectal screening program is about to
      be introduced in order to improve the extremely high mortality rate of colorectal
      cancer (CRC). AIM: The aim of our study was to summarize experiences and assess
      short-term efficacy of the population-based pilot colorectal screening program in
      2015 in Csongrad County, Hungary. PATIENTS AND METHOD: Asymptomatic individuals
      between the ages of 50 and 70 with average risk of colorectal cancer participated
      in the program that was based on the two-step screening method (i.e. immune fecal
      blood test and colonoscopy). The short-term efficacy of the screening program was
      assessed as the change in total CRC incidence and initial tumor stage in the
      screening year (2015) compared to a control year (2013) in Szeged and its
      surroundings. Participation rate, positive predictive value of the screening
      methods and tumor detection rate was assessed. RESULTS: 22,130 individuals were
      invited, the participation rate was 46.4%. Immune fecal blood test proved to be
      non-negative in 1,343 cases (13%), screening colonoscopy was performed in 766 of
      them (7.5%). Total colonoscopy was performed in 711 individuals. Based on the
      reports, adenoma was detected in 358 (50.3%) and malignancy in 42 (5.9%)
      individuals. In the background population, the incidence of colon cancer was
      significantly higher (183 vs. 228; p = 0.026) and was diagnosed at significantly
      earlier stage (p = 0.002). Lymph node involvement was significantly lower in 2015
      (48.3% vs. 37.1%; p = 0.049). CONCLUSION: The Csongrad county population-based
      colorectal cancer screening was evidently successful on the short term
      considering participation rate, and the changes in CRC incidence and stage, thus
      its national extension is necessary. Orv Hetil. 2017; 158(42): 1658-1667.

PMID- 29037059
TI  - [Experimental study on the resistance to intraluminal pressure between handsewn
      and stapled anastomosis. In vitro experimental study].
AB  - : Intoduction and aim: The aim of the study was to compare the resistance to
      pressure of stapled and manually handsewn intestinal suture lines on in vitro pig
      intestine model. METHOD: We performed different types of stapled and manual
      sutures and the pressure level was measured using a differential pressure
      manometer. RESULTS: Although the hand-sewn end-to-end suture turned out to be the
      most resistant to pressure, statistical analysis revealed no significant
      differences compared to stapled suture (p = 0.49). In stump closure techniques,
      we observed a statistically high significance in resistance to pressure in the
      favour of manual stump closure (p = 0.004).Regarding side-to-side sutures we did
      not find any statistically significant differences in resistance to pressure
      between the techniques (p = 0.06). CONCLUSION: We can conclude that regarding the
      stump closure, the most resistant to pressure is the hand-sewn procedure, but in
      the other types of anastomosis, no significant differences was found between the
      stapled and hand-sewn techniques. Orv Hetil. 2017; 158(42): 1674-1680.

PMID- 29037061
TI  - [The role of steroids in oncological practice].
AB  - Corticosteroids are a class of steroid hormones that are produced and disengage
      in the adrenal cortex. Traditionally natural and synthetic corticosteroids are
      used for diagnosing and treating dysfunctions of the adrenal cortex and treating
      inflammatory and immunological diseases. Their use is also widespread in
      oncological practice. Corticosteroids are indispensable in palliative care, in
      certain urgent oncological cases, as premedication of some chemotherapies and
      last but not least they have a key role in the secondary hormonal manipulations
      of metastatic castrate-resistant prostate cancer. The purpose of our review is to
      describe and compare the effects of different agents in oncological practice, to
      give a detailed account of the above mentioned indications and would also like to
      draw attention to the possible side effects of a long-term steroid treatment. Orv
      Hetil. 2017; 158(42): 1651-1657.

PMID- 29037062
TI  - Quantum dot-based lateral-flow immunoassay for rapid detection of rhein using
      specific egg yolk antibodies.
AB  - The lateral-flow immunoassays based on novel fluorescent labels have been
      receiving increasing attention. Here, we developed a rapid, quantitative, lateral
      flow immunoassay for rapid and accurate detection of rhein (RHE). The competitive
      immunoassay used anti-RHE IgY (immunoglobulin of yolk) probe conjugated with QDs
      as reporter. Our results showed that the immunochromatographic strip can be
      applied for qualitative and quantitative analysis of RHE in samples. For
      quantitative analysis, the strips were scanned by a membrane-strip reader, and a
      detection curve (y = -0.128ln(x) + 1.7627, correlation coefficient = 0.9792)
      representing the averages of the scanned data was obtained. The detection range
      was 80-5000 ng mL-1 and the qualitative-detection limit for RHE was 98.2 ng mL-1.
      To our knowledge, this is the first report of the quantitative detection of a
      natural product by QDs-IgY immunochromatography, which creates a new strategy to
      detect the harmful or index component of TCM and may be applied as a supplement
      or alternative to instrument detection.

PMID- 29037063
TI  - Barriers to Self-Management in Depressed Women With Type 2 Diabetes.
AB  - Purpose To describe the impact of family functioning on the self-management of
      type 2 diabetes (T2DM) and depression in a subsample of women who completed a
      randomized clinical trial using vitamin D3 (5000 or 50,000 IUs weekly) for
      depression treatment. Background Women are at higher risk for increased severity
      of T2DM when experiencing depression. Methods Narrative inquiry was used. A semi
      structured interview was conducted to understand helpful strategies and barriers
      in managing T2DM and depression. In addition, women were asked their meaning of
      family quality of life (FQOL). Results Twenty-one women participated after
      completion of the six-month final visit in the randomized clinical trial. The
      mean age was 55.2 years. Participants were 24% Hispanic, 48% African-American,
      and 52% Caucasian. The major themes generated related to family issues that
      impacted their self-management, yet participants did not want to "bring fault" to
      their families. Three themes emerged: (a) experience of family hardships-"it's
      been hard for me," (b) lack of disclosure to family about being depressed-"no
      point in talking to them," and (c) the need for connectedness with family and
      others-"the way it used to be... close as a family." Conclusion Family-centered
      approaches could address barriers to self-management. A "family lens" for
      practice and research may improve health outcomes.

PMID- 29037064
TI  - Outcome of Transurethral Resection of Bladder Tumor: Does Antiplatelet Therapy
      Really Matter? Analysis of a Retrospective Series.
AB  - INTRODUCTION: Transurethral resection of bladder tumor (TURBT) is considered to
      be at a moderate or high risk of bleeding during surgical procedure. The number
      of patients on antiplatelet (AP) drugs has been increasing; we wanted to assess
      their impact on the outcome of patients undergoing scheduled TURBT. MATERIALS AND
      METHODS: A retrospective assessment of noninferiority of 450 consecutive
      procedures performed between April 2013 and June 2015 was conducted. Patients
      were divided in two groups: naive or AP drug users. The primary endpoint was the
      average length of stay (ALOS). Noninferiority was set at 1 day. A subgroup
      analysis comparing the acetylsalicylic acid (ASA) group and clopidogrel group to
      the naive group was performed. Multivariate analysis was performed to find the
      determinants of a longer ALOS. Chi-square or Fisher tests were used to analyze
      categorical variables, and Student's or Mann-Whitney tests were used to analyze
      quantitative variables. RESULTS: We included 325 patients who underwent TURBT:
      117 received AP drugs (ASA, 85; clopidogrel, 32) and 208 were naive to AP drugs
      (of whom 117 were consecutively analyzed). The ALOSs were 2.5 days (naive group)
      and 2.9 days (AP group). The subgroup analysis showed ALOSs of 2.6 days (ASA
      group) and 3.7 days (clopidogrel group). Clopidogrel therapy (odds ratio = 4.1
      [1.7-9.6]) and the duration and depth of resection emerged as determinants of a
      longer ALOS in multivariate analysis. Perioperative management of AP therapies
      was achieved according to recommended practices. CONCLUSIONS: The ALOS of
      patients receiving AP drugs was not clinically different from naive patients.
      This result was identical for patients receiving ASA. However, clopidogrel
      increased the length of stay, making us question its use in perioperative
      management.

PMID- 29037065
TI  - Patterns of symptom development in patients with motor neuron disease.
AB  - OBJECTIVE: To investigate whether symptom development in motor neuron disease
      (MND) is a random or organized process. METHODS: Six hundred patients with
      amyotrophic lateral sclerosis (ALS), upper motor neuron (UMN) or lower motor
      neuron (LMN) phenotypes were invited for a questionnaire concerning symptom
      development. A binomial test was used to examine distribution of symptoms from
      site of onset. Development of symptoms over time was evaluated by Kaplan-Meier
      analysis. RESULTS: There were 470 respondents (ALS = 254; LMN = 100; UMN = 116).
      Subsequent symptoms were more often in the contralateral limb following
      unilateral limb onset (ALS: arms p = 1.05 * 10-8, legs p < 2.86 * 10-15; LMN
      phenotype: arms p = 6.74 * 10-9, legs p = 6.26 * 10-6; UMN phenotype: legs p =
      4.07 * 10-14). In patients with limb onset, symptoms occurred significantly
      faster in the contralateral limb, followed by the other limbs and lastly by the
      bulbar region. Patterns of non-contiguous symptom development were also reported:
      leg symptoms followed bulbar onset in 30%, and bulbar symptoms followed leg onset
      in 11% of ALS patients. CONCLUSIONS: Preferred spread of symptoms from one limb
      to the contralateral limb, and to adjacent sites appears to be a characteristic
      of MND phenotypes, suggesting that symptom spread is organized, possibly
      involving axonal connectivity. Non-contiguous symptom development, however, is
      not uncommon, and may involve other factors.

PMID- 29037066
TI  - Complications, Re-Intervention Rates, and Natural History of Residual Stone
      Fragments After Percutaneous Nephrolithotomy.
AB  - INTRODUCTION: The management of residual fragments (RFs) that persist after
      percutaneous nephrolithotomy (PCNL) has been poorly studied. Fragments have the
      potential to grow or cause symptoms. The aim of this study was to follow patients
      with fragments after PCNL to identify predictors of stone-related events (re
      interventions and complications) after PCNL. PATIENTS AND METHODS: Data were
      retrospectively collected from patients who underwent surgery from 2008 to 2013
      at our hospital. Patients with fragments of any size on postoperative day 1
      computed tomography of the kidney, ureter, and bladder radiograph (CT-KUB) were
      included, and patients with planned secondary interventions were excluded.
      Subgroup analysis was performed on subjects with CT-plain X-ray to determine
      fragment growth or passage. RESULTS: Of the 658 patients who received a
      postoperative CT-KUB on day 1, 299 patients (45%) had fragments that were 1 mm or
      larger. From this, 263 patients met the study criteria and were included. The
      size of fragments, using a 4 mm cutoff, did not predict the passage of fragments
      (p = 0.173) or growth (p = 0.572). On multivariable logistic regression analysis,
      previous history of renal stones and size of fragment were found to be predictive
      for stone-related events (p = 0.002 and 0.027, respectively). Kaplan-Meier
      analysis identified patients with fragments >4 mm having a shorter survival time
      before the occurrence of stone-related events (p = 0.044). CONCLUSIONS: The true
      stone-free rate was 55% after PCNL. However, 82.5% were stone free or had RFs 4
      mm or less, which correlates with previous studies. Larger RFs had higher rates
      of stone-related events and shorter time to occurrence of stone-related events.
      The growth and spontaneous passage of RFs was independent of RF size, emphasizing
      the importance of obtaining a stone-free status after PCNL.

PMID- 29037067
TI  - Design and application of tumor prediction model based on statistical method.
AB  - Two prediction models for tumor prediction based on logistic regression and BP
      neural network were proposed in this paper; a sensitivity analysis of risk
      factors was also conducted. The two protocols will be implemented in the R
      language and demonstrated with relevant lung cancer data. Additionally, the two
      models are compared, verifying their accuracy and feasibility. Finally, a
      function is combined with R language, which can quickly achieve the above two
      programs. It is set up to obtain the tumor prediction model and the risk factors
      on the degree of correlation of the size of the disease. This method is
      convenient and practical and we hope it can be applied in the early discovery of
      cancer during future medicine.

PMID- 29037068
TI  - Editorial.

PMID- 29037069
TI  - Factor analysis of the Zarit Burden Interview in family caregivers of patients
      with amyotrophic lateral sclerosis.
AB  - OBJECTIVE: The Zarit Burden Interview has been used in many studies to assess
      caregiver burden in family caregivers of patients with amyotrophic lateral
      sclerosis, but the factor structure of the Zarit Burden Interview in the
      caregivers of amyotrophic lateral sclerosis patients is unknown. The aim of this
      study was to explore the factor structure of the Zarit Burden Interview in family
      caregivers of amyotrophic lateral sclerosis patients using exploratory factor
      analysis. METHODS: The exploratory factor analysis was performed using
      generalized least squares with oblique rotation in a sample of 202 family
      caregivers. RESULTS: Three factors had an eigenvalue greater than 1 and accounted
      for 60.33% of the total variance. The three factors were named as follows:
      (factor 1) "Social restrictions" (items 2, 3, and 10-15); (factor 2) "Self
      criticism" (items 20-21); and (factor 3) "Anger and frustration" (items 1, 4-6,
      9, and 16-19). The correlation between factors 1 and 3 was much higher (r = 0.79)
      than that between factors 1 and 2 (r = 0.14) or factors 2 and 3 (r = 0.15).
      CONCLUSION: The findings of this study enriched our understanding of several
      meaningful dimensions of the caregiving burden in caregivers of an amyotrophic
      lateral sclerosis population and provided opportunities for future intervention.

PMID- 29037070
TI  - Melatonin promotes self-renewal of nestin-positive pancreatic stem cells through
      activation of the MT2/ERK/SMAD/nestin axis.
AB  - Although melatonin has been shown to exhibit a wide variety of biological
      functions, its effects on promotion of self-renewal in pancreatic stem cells
      remain unknown. In this study, we incubated murine pancreatic stem cells (PSCs)
      with various concentrations of melatonin (0.01, 0.1, 1, 10 or 100 MUM) to screen
      for the optimum culture medium for increasing cell proliferation. We found that
      10 MUM melatonin can significantly increase proliferation and enhance expression
      of a stem cell marker, nestin, in PSCs via melatonin receptor 2 (MT2). Thus, we
      used 10 MUM melatonin to study the melatonin-mediated molecular mechanisms of
      cell proliferation in PSCs. We applied extracellular signal-regulated kinase
      (ERK) pathway inhibitor SCH772984 and transforming growth factor beta (TGF-beta)
      pathway inhibitor SB431542, along with interfering RNAs siERK1, siERK2, siSmad2,
      siSmad3, siSmad4 and siNestin, to melatonin-treated PSCs to research the roles of
      these genes in self-renewal. The results revealed a novel molecular mechanism by
      which melatonin promotes self-renewal of PSCs: a chain reaction in the
      MT2/ERK/SMAD/nestin axis promoted the aforementioned self-renewal as well as
      inhibited differentiation. In addition, upregulation of nestin created a positive
      feedback loop in the regulation of the transforming growth factor beta 1 (TGF
      beta1)/SMADs pathway by promoting expression of Smad4. Conversely, knockdown of
      nestin significantly suppressed the proliferative effect in melatonin-treated
      PSCs. These are all novel mechanisms through which the ERK pathway cooperatively
      crosstalks with the SMAD pathway to regulate nestin expression, thereby enhancing
      self-renewal in PSCs.

PMID- 29037071
TI  - Evidence-Based Review of BioBran/MGN-3 Arabinoxylan Compound as a Complementary
      Therapy for Conventional Cancer Treatment.
AB  - INTRODUCTION: Conventional cancer treatment, including surgery, chemotherapy, and
      radiotherapy, may not be sufficient to eradicate all malignant cells and prevent
      recurrence. Intensive treatment often leads to a depressed immune system, drug
      resistance, and toxicity, hampering the treatment outcomes. BioBran/MGN-3
      Arabinoxylan is a standardized arabinoxylan concentrate which has been proposed
      as a plant-based immunomodulator that can restore the tumor-induced disturbance
      of the natural immune system, including natural killer cell activity to fight
      cancer, complementing conventional therapies. OBJECTIVES: To comprehensively
      review the available evidence on the effects and efficacies of MGN-3 as a
      complementary therapy for conventional cancer treatment. METHODS: Systematic
      search of journal databases and gray literature for primary studies reporting the
      effects of MGN-3 on cancer and cancer treatment. RESULTS: Thirty full-text
      articles and 2 conference abstracts were included in this review. MGN-3 has been
      shown to possess immunomodulating anticancer effects and can work synergistically
      with chemotherapeutic agents, in vitro. In murine models, MGN-3 has been shown to
      act against carcinogenic agents, and inhibit tumor growth, either by itself or in
      combination with other anticancer compounds. Fourteen successful MGN-3 treated
      clinical cases were found. Eleven clinical studies, including 5 nonrandomized,
      pre-post intervention studies and 6 randomized controlled trials (RCTs) were
      located. Reported effects include enhanced immunoprofile, reduced side effects,
      improved treatment outcomes; one RCT established significantly increased survival
      rates. There are no reports on adverse events on MGN-3. Most of the clinical
      trials are small studies with short duration. CONCLUSION: There is sufficient
      evidence suggesting MGN-3 to be an effective immunomodulator that can complement
      conventional cancer treatment. However, more well-designed RCTs on MGN-3 are
      needed to strengthen the evidence base.

PMID- 29037072
TI  - High perceived caregiver burden for relatives of patients following hip fracture
      surgery.
AB  - PURPOSE: To determine the profile of the main informal caregivers, the evolution
      of the caregiver burden, and the influencing factors of caregiver burden at 1
      year after hip fracture surgery. METHODS: In this prospective cohort study, a
      total of 172 informal caregivers of patients were interviewed at four points
      during 1 year following hip fracture surgery in a regional hospital in southern
      Spain. The perceived caregiver burden was assessed using the Caregiver Strain
      Index (0-13 points). RESULTS: The mean (Standard Deviation) age of the 172
      caregivers was 56 (13) years, of which 133 (77%) were woman and 94 (55%) were
      daughters of the patient. Seventy-nine of the 172 (46%) caregivers perceived a
      high level of burden (>= 7 points on the Caregiver Strain Index) at the hospital.
      The corresponding numbers with perceived high level of burden at 1-month, 3
      months, and 1-year were 87 (50%), 61 (36%), and 45 (26%) caregivers. A low pre
      fracture functional status, post-operative complications, older age of patients,
      and younger age of caregivers negatively influence caregiver burden at 1-year.
      CONCLUSIONS: The main caregiver is predominantly female and is most often the
      daughter of the patient. New treatment strategies such as the support and
      training of the caregivers in patient handling during hospital stay could be
      carried out to reduce caregiver burden. Implications for rehabilitation The main
      caregiver of a hip fracture patient is usually a woman who is the daughter of the
      patient, and reducing her burden of care should be included as one of the
      objectives of rehabilitation treatment. The caregivers of hip fracture patients
      must be considered as part of the treatment during the patient's recovery period,
      and patient handling training should be provided to the caregivers of hip
      fracture patients during the hospital stay to prepare the process of going back
      home. The caregivers of older patients, those with a low pre-fracture functional
      level, and of those who suffered post-operative complications, should receive
      more attention prior to hospital discharge and receive more assistance at home to
      reduce caregiver burden.

PMID- 29037073
TI  - Physical inactivity and cognitive impairment in Korean older adults: gender
      differences in potential covariates.
AB  - BACKGROUND: Physical inactivity is one major lifestyle risk factor of mild
      cognitive impairment with ageing. AIM: To investigate whether or not potential
      covariates modulate the association between physical activity (PA) and cognitive
      impairment in older adults. SUBJECTS AND METHODS: Data from 10 245 Korean older
      adults (5817 women) were used. RESULTS: High PA older adults were younger and
      longer educated and had lower comorbidity and depression than low PA older
      adults. Compared with low PA men, moderate PA men only had a significantly lower
      odds-ratio (OR) and 95% confidence interval (95% CI) (OR = 0.795, 95% CI = 0.654
      ~ 0.965, p = 0.021) for having cognitive impairment, even after adjusting for
      measured covariates, which was no longer significant when additionally adjusted
      for comorbidity (OR = 0.862, 95% CI = 0.707 ~ 1.051, p = 0.143). Compared with
      low PA women, moderate and high PA women had significantly lower risks of
      cognitive impairment (OR = 0.830, 95% CI = 0.712 ~ 0.969, p = 0.018 and OR =
      0.784, 95% CI = 0.651 ~ 0.943, p = 0.010, respectively), even after adjusting for
      the measured covariates including comorbidity, which was no longer significant
      when additionally adjusted for depression (OR = 0.897, 95% CI = 0.776 ~ 1.049, p
      = 0.173 and OR = 0.919, 95% CI = 0.761 ~ 1.111, p = 0.385, respectively).
      CONCLUSION: These findings suggest that gender differences in the covariates
      modulate the relationship between physical activity and cognitive decline in
      older Korean adults.

PMID- 29037075
TI  - Optimal distance of multi-plane sensor in three-dimensional electrical impedance
      tomography.
AB  - Electrical impedance tomography (EIT) is a visual imaging technique for obtaining
      the conductivity and permittivity distributions in the domain of interest. As an
      advanced technique, EIT has the potential to be a valuable tool for continuously
      bedside monitoring of pulmonary function. The EIT applications in any three
      dimensional (3 D) field are very limited to the 3 D effects, i.e. the
      distribution of electric field spreads far beyond the electrode plane. The 3 D
      effects can result in measurement errors and image distortion. An important way
      to overcome the 3 D effect is to use the multiple groups of sensors. The aim of
      this paper is to find the best space resolution of EIT image over various
      electrode planes and select an optimal plane spacing in a 3 D EIT sensor, and
      provide guidance for 3 D EIT electrodes placement in monitoring lung function. In
      simulation and experiment, several typical conductivity distribution models, such
      as one rod (central, midway and edge), two rods and three rods, are set at
      different plane spacings between the two electrode planes. A Tikhonov
      regularization algorithm is utilized for reconstructing the images; the relative
      error and the correlation coefficient are utilized for evaluating the image
      quality. Based on numerical simulation and experimental results, the image
      performance at different spacing conditions is evaluated. The results demonstrate
      that there exists an optimal plane spacing between the two electrode planes for 3
      D EIT sensor. And then the selection of the optimal plane spacing between the
      electrode planes is suggested for the electrodes placement of multi-plane EIT
      sensor.

PMID- 29037074
TI  - Reference data for ultrasound bone characteristics in Hungarian children aged 7
      19 years.
AB  - : Backround: Osteoporosis is a common disease and physical activity (PA) has a
      favourable influence on bone status. AIM: To establish normative data for
      calcaneal quantitative ultrasound (QUS) bone characteristics in children and to
      analyse the relationships between PA, anthropometric and bone parameters.
      SUBJECTS AND METHODS: Hungarian children aged 7-19 (n = 2674; 1325 girls, 1349
      boys) provided PA, anthropometric and bone data. QUS parameters were registered
      with Sonost3000 densitometer (speed of sound: SOS, m/s; broadband ultrasound
      attenuation: BUA, dB/MHz; bone quantity index (BQI = alphaSOS + betaBUA).
      Reference centiles of QUS parameters were constructed by LMS method. Multivariate
      linear regression models were used to analyse the relationships. RESULTS: QUS
      bone parameters increased with age. There were no gender differences, except in
      11- and 19-year-old children, where boys showed higher values. SOS (1497.15 +/-
      15.72 vs 1494.05 +/- 14.81 m/s) and BQI (65.31 +/- 16.71 vs 62.26 +/- 15.78) were
      higher in athletic children. The regression model revealed significant relations
      between SOS and age, relative muscle mass and PA; BUA correlated with gender,
      morphological age, BMI, relative muscle mass and PA. CONCLUSIONS: Changes in the
      bone parameters among 7-19-year-old Hungarian children depended on age,
      anthropometric dimensions and the level of PA. The normative data could be used
      for monitoring QUS bone parameters in children, leading to more effective
      interventions for healthy bones.

PMID- 29037076
TI  - Atlantic Canada Needs a Human Milk Bank.

PMID- 29037078
TI  - The accuracy of neck circumference for assessing overweight and obesity: a
      systematic review and meta-analysis.
AB  - CONTEXT: Neck circumference (NC) has been suggested as an alternative measure to
      screen for excess body weight. OBJECTIVE: The aim of this study was to
      demonstrate the accuracy of neck circumference (NC) as a measure for assessing
      overweight and obesity in both sexes in different age groups. METHODS: Detailed
      individual search strategies were developed for each of the following
      bibliographic databases: Cochrane, LILACS, PubMed/MEDLINE, Science Direct, Scopus
      and Web of Science. The QUADAS-2 checklist was used to assess the methodology of
      the studies included. RESULTS: Thirty-eight assessments were performed in 11
      articles according to age, sex and weight status. Using sensitivity and
      specificity, 27 assessments (71.0%) considered NC an accurate measure to diagnose
      overweight and obesity. The best sensitivity and specificity were found for the
      age >19 years (82.0%, 82.0%), female (80.0%, 73.0%), and obese (80.0%, 85.0%)
      categories. CONCLUSION: NC is an accurate tool for assessing overweight and
      obesity in males and females of different age groups and could be used to screen
      for excess body weight in routine medical practice or epidemiological studies. It
      is also believed that more studies will permit the creation of a reference
      dataset of NC cut-off values for world populations.

PMID- 29037079
TI  - Development of novel adjustable focus head mount display for concurrent image
      guided treatment applications.
AB  - PURPOSE: A conventional see-through head mount display contains many optical
      lenses, which can be problematic in image-guided treatment applications due to
      its size, weight, structure, and focus limitation. Therefore, we have designed a
      new type of see-through head mount display with a reduced number of optical
      lenses and an adequate optical resolution that can be utilized for image-guided
      treatment applications. MATERIALS AND METHODS: A new type of adjustable focus
      head mount display with expanded virtual images and an external treatment space
      that can be provided to the eyes of a user by enlarging the images of a small
      display is designed and investigated in this study. This type of head mount
      display can be used in image-guided treatment applications because of the dual
      paths of imaging and treatment from the optical systems. Therefore, this system
      with an adjustable focus function can aid doctors in obtaining images for the
      treatment of the eyes of patients because every patient has a unique pupil size.
      RESULTS: The results of the adjustable focus see-through head mount display
      showed distortion values of +0.36% in the +1 diopter location and -0.55% in the 
      4 diopter location, and there are less significant modulation transfer function
      differences within the +/-5 diopter locations. CONCLUSIONS: Low optical
      distortions within +/-0.5 diopters can help doctors image the eye conditions of
      patients through fewer image processing techniques. Therefore, the designed
      adjustable focus head mount display can provide low optical aberrations and high
      optical modulation transfer function resolutions for image-guided treatment
      applications.

PMID- 29037081
TI  - Editorial Comment on: In Vitro Comparison of Stone Fragmentation When Using
      Various Settings with Modern Variable Pulse Holmium Lasers by Bell et al. (From:
      Bell JR, Penniston KL, Nakada SY, J Endourol 2017;31:1067-1072).

PMID- 29037083
TI  - Cervical cancer histology image identification method based on texture and lesion
      area features.
AB  - The issue of an automated approach for detecting cervical cancer is proposed to
      improve the accuracy of recognition. Firstly, the cervical cancer histology
      source images are needed to use image preprocessing for reducing the impact
      brought by noise of images as well as the impact on subsequent precise feature
      extraction brought by irrelevant background. Secondly, the images are grouped
      into ten vertical images and the information of texture feature is extracted by
      Grey Level Co-occurrence Matrix (GLCM). GLCM is an effective tool to analyze the
      features of texture. The textures of different diseases in the source image of
      Cervical Cancer Histology (such as contrast, correlation, entropy, uniformity and
      energy, etc.) can all be obtained in this way. Thirdly, the image is segmented by
      using K-means clustering and Marker-controlled watershed Algorithm. And each
      vertical image is divided into three layers to calculate the areas of different
      layers. Based on GLCM and lesion area features, the tissues are investigated with
      segmentation by using Support Vector Machine (SVM) method. Finally, the results
      show that it is effective and feasible to recognize cervical cancer by automated
      approach and verified by experiment.

PMID- 29037082
TI  - The D313Y variant in the GLA gene - no evidence of a pathogenic role in Fabry
      disease.
AB  - Fabry disease is an X- linked inherited lysosomal storage disease caused by
      mutations in the GLA gene encoding the lysosomal enzyme alpha-galactosidase A
      (alpha-Gal A). The possible pathological significance of the D313Y variant in the
      GLA gene has not been verified and it may be a Fabry variant. Our aim was to
      elucidate whether the presence of the D313Y variant influenced the alpha-Gal A
      activity or resulted in Fabry symptoms or Fabry organ involvement. In two Danish
      families the presence of the D313Y variant did not result in reduced alpha-Gal A
      activity or clinical Fabry manifestations in males, and the presence in Fabry
      females did not significantly enhance the phenotype of a known causative mutation
      in the GLA gene (G271S). Our findings indicate that the D313Y variant is not
      causative to nor enhancing Fabry disease phenotype. The D313Y variant in the GLA
      gene was not disease causative in 2 Danish families. Investigating male family
      members were crucial in excluding the Fabry phenotype, and thus very important
      for proper genetic counceling of all family members, as well as overdiagnosing a
      devastating genetic disease.

PMID- 29037085
TI  - Luteal phase serum progesterone levels after GnRH-agonist trigger - how low is
      still high enough for an ongoing pregnancy?
AB  - In the past years, individualization of assisted reproductive technique (ART)
      treatment is increasingly common to customize the treatment protocol to the
      patient's specific conditions. The use of GnRH-agonist for final oocyte
      maturation in a gonadotropin-releasing hormone (GnRH)-antagonist protocol is the
      best approach to reduce the risk for ovarian hyperstimulation in high responder
      patients. However, due to severe luteolysis, the reproductive outcome with this
      approach in combination with the use of vaginal progesterone as luteal phase
      support, was poor. Cycle segmentation as alternative to a fresh transfer requires
      embryo freezing which might not be applicable to all patients due to various
      reasons. The concept of luteal coasting monitors the progesterone-level closely
      and human chorionic gonadotropin (hCG) for rescue of the corpora lutea is
      administered when the progesterone-level drops below a certain threshold.
      However, the lower range of progesterone levels in the early luteal phase after
      GnRH-agonist trigger, which is compatible with achieving and maintaining a
      pregnancy, is unknown. This case-series demonstrates, that ongoing pregnancies
      can be achieved even with a progesterone-level below 15 ng/ml in the early luteal
      phase with the timely administration of an hCG-rescue bolus. With the concept of
      luteal coasting, individualization of the luteal phase support according to the
      patient's specific luteolysis pattern is possible.

PMID- 29037084
TI  - Electron Paramagnetic Resonance Measurements of Reactive Oxygen Species by Cyclic
      Hydroxylamine Spin Probes.
AB  - SIGNIFICANCE: Oxidative stress contributes to numerous pathophysiological
      conditions such as development of cancer, neurodegenerative, and cardiovascular
      diseases. A variety of measurements of oxidative stress markers in biological
      systems have been developed; however, many of these methods are not specific, can
      produce artifacts, and do not directly detect the free radicals and reactive
      oxygen species (ROS) that cause oxidative stress. Electron paramagnetic resonance
      (EPR) is a unique tool that allows direct measurements of free radical species.
      Cyclic hydroxylamines are useful and convenient molecular probes that readily
      react with ROS to produce stable nitroxide radicals, which can be quantitatively
      measured by EPR. In this work, we critically review recent applications of
      various cyclic hydroxylamine spin probes in biology to study oxidative stress,
      their advantages, and the shortcomings. Recent Advances: In the past decade, a
      number of new cyclic hydroxylamine spin probes have been developed and their
      successful application for ROS measurement using EPR has been published. These
      new state-of-the-art methods provide improved selectivity and sensitivity for in
      vitro and in vivo studies. CRITICAL ISSUES: Although cyclic hydroxylamine spin
      probes EPR application has been previously described, there has been lack of
      translation of these new methods into biomedical research, limiting their
      widespread use. This work summarizes "best practice" in applications of cyclic
      hydroxylamine spin probes to assist with EPR studies of oxidative stress. FUTURE
      DIRECTIONS: Additional studies to advance hydroxylamine spin probes from the
      "basic science" to biomedical applications are needed and could lead to better
      understanding of pathological conditions associated with oxidative stress.
      Antioxid. Redox Signal. 28, 1433-1443.

PMID- 29037086
TI  - Measles and rubella elimination: learning from polio eradication and moving
      forward with a diagonal approach.
AB  - INTRODUCTION: In 1988, an estimated 350,000 children were paralyzed by polio and
      125 countries reported polio cases, the World Health Assembly passed a resolution
      to achieve polio eradication by 2000, and the Global Polio Eradication Initiative
      (GPEI) was established as a partnership focused on eradication. Today, following
      eradication efforts, polio cases have decreased >99% and eradication of all three
      types of wild polioviruses is approaching. However, since polio resources
      substantially support disease surveillance and other health programs, losing
      polio assets could reverse progress toward achieving Global Vaccine Action Plan
      goals. Areas covered: As the end of polio approaches and GPEI funds and capacity
      decrease, we document knowledge, experience, and lessons learned from 30 years of
      polio eradication. Expert commentary: Transitioning polio assets to measles and
      rubella (MR) elimination efforts would accelerate progress toward global
      vaccination coverage and equity. MR elimination feasibility and benefits have
      long been established. Focusing efforts on MR elimination after achieving polio
      eradication would make a permanent impact on reducing child mortality but should
      be done through a 'diagonal approach' of using measles disease transmission to
      identify areas possibly susceptible to other vaccine-preventable diseases and to
      strengthen the overall immunization and health systems to achieve disease
      specific goals.

PMID- 29037087
TI  - A label-free technique for accurate detection of nucleic acid-based self-avoiding
      molecular recognition systems supplemented multiple cross-displacement
      amplification and nanoparticles based biosensor.
AB  - Here, we devised a novel isothermal technique on the basis of standard multiple
      cross-displacement amplification (MCDA), which is assisted with self-avoiding
      molecular recognition system (SAMRS) components and antarctic thermal-sensitive
      uracil-DNA-glycosylase enzyme (AUDG), termed AUDG-SAMRS-MCDA. To enable product
      detection on the dipsticks, we firstly developed an analysis strategy, which did
      not require the labelled primers or probes, and thus, the analysis system avoids
      the false-positive results arising from undesired hybridization (between two
      labelled primers, or the labelled probe and primer). The SAMRS components are
      incorporated into MCDA primers for improve the assay's specificity, which can
      prevent the false-positive results yielding from off-target hybrids, undesired
      interactions between (hetero-dimer) or within (self-dimerization) primers. Two
      additional components (AUDG enzyme and dUTP) were added into the reaction
      mixtures, which were used for removing the false-positive results generating from
      carryover contamination, and thus, the genuine positives results were produced
      from the amplification of target templates. For the demonstration, the label-free
      AUDG-SAMRS-MCDA technique was successfully applied to detect Pseudomonas
      aeruginosa from pure culture and blood samples. As a proof-of-concept technique,
      the label-free AUDG-SAMRS-MCDA method can be reconfigured to detect different
      target sequences by redesigning the specific primers.

PMID- 29037088
TI  - Physical fitness and prior physical activity are both associated with less
      cortisol secretion during psychosocial stress.
AB  - BACKGROUND: Evidence linking fitness and decreased psychosocial stress comes from
      studies of athletes and typically relies upon self-report measures. Furthermore,
      there is little evidence regarding the impact of physical activity (PA) prior to
      a stressor. The aims of this study were to determine whether fitness and prior PA
      influence cortisol concentrations during psychosocial stress. METHODS: Seventy
      five non-athletic participants took part in a submaximal walk prior to the Trier
      Social Stress Test for Groups (TSST-G). During the walk, fitness was assessed
      using heart rate (HR). A further 89 participants took part in the TSST-G without
      the walk. Stress responsiveness was assessed using salivary cortisol collected at
      10-min intervals on seven occasions. RESULTS: Hierarchical multiple regression
      revealed that average walking HR accounted for 9% of the variance in cortisol
      secretion (P = .016), where a higher HR was associated with higher cortisol
      secretion. Between-subjects ANCOVA revealed that the walking group had a
      significantly lower cortisol secretion than the non-walking group (P = .009).
      CONCLUSIONS: These findings indicate that fitter individuals have reduced
      cortisol secretion during psychosocial stress. They also indicate that prior PA
      can reduce cortisol concentrations during psychosocial stress and are suggestive
      of a role of PA in reducing the impact of stress on health.

PMID- 29037089
TI  - Patient-Reported Outcomes in Nephrolithiasis: Can We Do Better?
AB  - PURPOSE: Nephrolithiasis contributes significantly to the worldwide healthcare
      burden. Patient-reported outcome measures (PROMs) are widely recognized as
      important outcome measures for patient-centered care. We sought to summarize what
      is currently known about PROMs in urinary stone disease and to characterize use
      of PROMs in randomized controlled trials (RCTs) for nephrolithiasis. MATERIALS
      AND METHODS: Health-related quality of life (HRQOL) in patients with
      nephrolithiasis is reviewed. A search of both MEDLINE and EMBASE databases for
      RCTs in nephrolithiasis was performed to assess utilization of PROMs in these
      trials. All searches were for articles published between 1990 and 2014. Two
      independent reviewers reviewed all abstracts to determine inclusion for full-text
      review, with disagreements reviewed by a separate arbitrator. RESULTS: Validated
      methods for collecting PROMs include symptom diaries, pain scales, and validated
      HRQOL instruments. HRQOL is impacted in patients with nephrolithiasis and may be
      related to gender, proximity of a recent colic episode, or treatment modality.
      One validated instrument has been created in the nephrolithiasis population,
      while a treatment-specific questionnaire on ureteral stents has also been
      developed. PROMs are variably reported in RCTs for nephrolithiasis. Few trials
      utilize validated HRQOL instruments and none utilizes a disease-specific
      instrument. CONCLUSIONS: HRQOL is diminished in patients with urolithiasis,
      especially in times near to an acute stone event. Only one validated HRQOL
      instrument exists specific to nephrolithiasis. No validated instrument exists to
      assess the outcomes from different management options for renal and ureteral
      stones. Development of condition-specific PROMs instruments should aim to account
      for the heterogeneous and episodic nature of the disease and its treatment.
      Effective reporting of PROMs is lacking in the RCTs for nephrolithiasis. Future
      RCTs for urolithiasis standardize reporting of PROMs.

PMID- 29037090
TI  - Prevention and the state of knowledge of tick-borne diseases among orienteers in
      Poland.

PMID- 29037092
TI  - Evidence-based interventions of dichotic listening training, compensatory
      strategies and combined therapies in managing pupils with auditory processing
      disorders.
AB  - OBJECTIVE: The need to develop a measure of managing children with a single
      profile of auditory processing disorders (APDs), and differentiate between true
      and artefactual improvements necessitated the study. The study also sought to
      determine the efficacy of interventions - both single and combined on APD,
      against no-treatment. DESIGN: A randomised controlled trial of interventions
      (RCT) was adopted. Participants were randomly allocated to each of the
      intervention groups or the no intervention group. The 10 weeks intervention
      included 45 minutes three times a week therapeutic intervention on listening with
      noise and sound localisation ability in the home and school environments. STUDY
      SAMPLE: 80 pupils (7-11 years) with a single profile of APD participated in the
      study. RESULTS: Treatments were effective on the cocktail party and sound
      localisation. The best result was realised with the combined therapy (CT), and
      there was no significant difference in performance in the remaining treatment
      groups. CONCLUSION: The intervention groups were beneficial to pupils with APD
      and should be adopted by clinicians.

PMID- 29037094
TI  - The importance of context in medical education program evaluation.

PMID- 29037091
TI  - An anthropometric survey of US pre-term and full-term neonates.
AB  - BACKGROUND: Anthropometric data prove valuable for screening and monitoring
      various medical conditions. In young infants, however, only weight, length and
      head circumference are represented in publicly accessible databases. AIM: To
      characterise length and circumferential measures in pre-term and full-term
      infants up to 90 days post-natal. SUBJECTS AND METHODS: In eight US medical
      centres, trained raters recorded humeral, ulnar, femoral, tibial and fibular
      lengths along with mid-upper arm, mid-thigh, chest, abdominal and neck
      circumference. Data were pooled by post-menstrual age into 1-week intervals and
      population curves created using the lambda, mu and sigma (LMS) method. Goodness
      of-fit was assessed by examining de-trended quantile-quantile plots, Q statistics
      and fitted centiles overlaid on empirical centiles. RESULTS: In total, 2097
      infants were enrolled in this study with a mean +/- SD gestational age and post
      natal age of 37.1 +/- 3.3 weeks and 27.3 +/- 25.3 days, respectively. A re-scale
      option was used to describe all curves. The resultant models reliably
      characterised anthropometric measures from 33-52 weeks PMA, with less certainty
      at the extremes (27-55 weeks). CONCLUSION: The population curves generated under
      this investigation expand existing reference data on a comprehensive set of
      anthropometric traits in infants through the first 90 days post-natal.

PMID- 29037093
TI  - Less periprosthetic bone loss following the anterolateral approach to the hip
      compared with the direct lateral approach.
AB  - Background and purpose - The loss of bone mineral in the proximal femur following
      hip arthroplasty may increase the fracture risk around uncemented stems. We
      hypothesized that the surgical approach to the hip might influence bone mineral
      changes around the femoral stem in patients with a femoral neck fracture (FNF).
      Patients and methods - This was a pre-specified subgroup analysis (n = 51) of an
      ongoing randomized trial (n = 120) in patients with FNF. Participants were
      allocated to an uncemented hemiarthroplasty inserted through a direct lateral
      (Hardinge) approach or an anterolateral (modified Watson-Jones) approach. The 51
      patients (mean age 83 (70-90) years, 33 women) were measured by dual-energy X-ray
      absorptiometry (DXA) to assess changes in periprosthetic bone mineral density
      (BMD). Results - The mean change in total BMD differed between groups at 12
      months in favor of the anterolateral group (4.8%, 95% CI 0.0-9.6; p = 0.05). DXA
      at 3 months displayed BMD loss in the proximal Gruen zones in the lateral group
      compared with the anterolateral group. Zone 1 (-5.0% vs. 2.7%), zone 2 (-4.3% vs.
      4.1%), zone 6 (-6.5% vs. 0.0%) and zone 7 (-11% vs. -2.4%, all p < 0.05).
      Interpretation - DXA measurements in this study indicate that surgical approach
      to the hip influences periprosthetic BMD. Clinical implications remain uncertain.
      Our conclusions should be interpreted with caution as we did not perform
      adjustments for multiple tests, possibly leading to inflation of false-positive
      findings.

PMID- 29037095
TI  - Biological dose and complication probabilities for the rectum and bladder based
      on linear energy transfer distributions in spot scanning proton therapy of
      prostate cancer.
AB  - BACKGROUND: The increased linear energy transfer (LET) at the end of the Bragg
      peak causes concern for an elevated and spatially varying relative biological
      effectiveness (RBE) of proton therapy (PT), often in or close to dose-limiting
      normal tissues. In this study, we investigated dose-averaged LET (LETd)
      distributions for spot scanning PT of prostate cancer patients using different
      beam angle configurations. In addition, we derived RBE-weighted (RBEw) dose
      distributions and related normal tissue complication probabilities (NTCPs) for
      the rectum and bladder. MATERIAL AND METHODS: A total of 21 spot scanning proton
      plans were created for each of six patients using a prescription dose of 78
      Gy(RBE1.1), with each plan using two 'mirrored' beams with gantry angles from 110
      degrees /250 degrees  to 70 degrees /290 degrees , in steps of 2 degrees .
      Physical dose and LETd distributions were calculated as well as RBEw dose
      distributions using either RBE = 1.1 or three different variable RBE models. The
      resulting biological dose distributions were used as input to NTCP models for the
      rectum and bladder. RESULTS: For anterior oblique (AO) configurations, the rectum
      LETd volume and RBEw dose increased with increasing angles off the lateral
      opposing axis, with the RBEw rectum dose being higher than for all posterior
      oblique (PO) configurations. For PO configurations, the corresponding trend was
      seen for the bladder. Using variable RBE models, the rectum NTCPs were highest
      for the AO configurations with up to 3% for the 80 degrees /280 degrees 
      configuration while the bladder NTCPs were highest for the PO configurations with
      up to 32% for the 100 degrees /260 degrees . The rectum D1cm3 constraint was
      fulfilled for most patients/configurations when using uniform RBE but not for any
      patient/configuration with variable RBE models. CONCLUSIONS: Compared to using
      constant RBE, the variable RBE models predicted increased biological doses to the
      rectum, bladder and prostate, which in turn lead to substantially higher
      estimated rectum and bladder NTCPs.

PMID- 29037096
TI  - Fluoride toothpastes containing micrometric or nano-sized sodium trimetaphosphate
      reduce enamel erosion in vitro.
AB  - OBJECTIVE: To evaluate the effect of fluoride toothpastes supplemented with
      micrometric or nano-sized sodium trimetaphosphate (TMP or TMPnano, respectively)
      on enamel erosion in vitro, as well as the influence of salivary acquired
      pellicle and saliva. MATERIAL AND METHODS: Bovine enamel blocks (n = 120) were
      randomly assigned into the following experimental toothpastes: no F/TMP/TMPnano
      (Placebo); 1100 ppm F (1100 ppm F); 1100 ppm F plus 3% TMP or 3% TMPnano (1100
      TMP or 1100 TMPnano, respectively) and 5000 ppm F (5000 ppm F). Erosive challenge
      was performed by immersion of the blocks in citric acid for 5 min, followed by 2
      h immersion in human or artificial saliva, 4*/day, during 5 days. After each
      erosive challenge, blocks were exposed to slurries of the toothpastes. Enamel
      erosion (um), surface hardness (SHf) and cross-sectional hardness (DeltaKHN) were
      analyzed as response variables and the data were submitted to two-way ANOVA,
      followed by the Student-Newman-Keuls test (p < .05). RESULTS: 1100 TMPnano
      significantly reduced enamel loss when compared to 1100 TMP (p = .002), reaching
      values similar to those promoted by 5000 ppm F (p = .96). 1100 ppm F presented
      significantly lower enamel loss than Placebo (p < .001), and higher than 1100 TMP
      (p < .001). Significantly higher SHf and lower DeltaKHN was observed for 1100
      TMPnano and 5000 ppm F when compared with the other groups (p < .001). The type
      of saliva did not influence enamel erosion, SHf and DeltaKHN for the groups
      treated with TMP-containing toothpastes. CONCLUSION: The addition of 3% TMPnano
      to 1100 ppm F toothpastes significantly increases the protective effect against
      enamel erosion in vitro when compared with its counterparts with micrometric TMP
      or without TMP. This effect was not influenced by the presence of acquired enamel
      pellicle and saliva.

PMID- 29037097
TI  - Obstetrical and neonatal outcomes of pregnancies complicated by endometriosis.
AB  - OBJECTIVE: Endometriosis is defined as the presence of endometrial-like tissue
      outside the uterus, associated with pelvic pain and subfertility, affecting 0.6
      10% of the general female population. The association between endometriosis and
      obstetrical outcomes is not well established. We aimed to evaluate whether
      endometriosis is associated with a higher incidence of obstetrical and neonatal
      complications. STUDY DESIGN: A retrospective cohort study of all deliveries in a
      university-affiliated tertiary hospital (2007-2014). Eligibility was limited to
      women with previously diagnosed endometriosis and singleton pregnancies. Fetuses
      or neonates diagnosed with structural or chromosomal anomalies were excluded. We
      compared labor and delivery outcomes and immediate neonatal outcomes among women
      with endometriosis compared with women without endometriosis. RESULTS: Overall,
      61,535 deliveries were eligible for analysis, of which 135 (0.002%) had
      endometriosis. Women with in the endometriosis group were characterized by higher
      maternal age, lower parity and higher nulliparity rate, and an earlier
      gestational age at delivery. Women with endometriosis had higher rate of failure
      of induction of labor (aOR 5.2, 95%CI 1.8-14.9), cesarean delivery (aOR 5.0,
      95%CI 3.3-7.4), postpartum hemorrhage (aOR 3.7, 95%CI 1.6-8.5), placenta accreta
      (aOR 6.24, 95%CI 2.20-17.67), postpartum hemoglobin <10 mg/dL (aOR 2.03, 95%CI
      1.31-3.14), and packed cell transfusion (aOR 3.66, 95%CI 1.94-6.91). No
      significant differences in neonatal outcomes were observed. CONCLUSIONS:
      Endometriosis is associated with higher risk of cesarean delivery and postpartum
      hemorrhage. Our findings suggest appropriate preparations for delivery, such as
      uterotonic agents and blood products, should be considered in these women.

PMID- 29037098
TI  - How do formative objective structured clinical examinations drive learning?
      Analysis of residents' perceptions.
AB  - INTRODUCTION: Although several studies have explored the relationship between
      learning and written tests, little is understood about how performance-based
      examinations influence learning. The purpose of this study was to explore how a
      formative objective structured clinical examination (OSCE) drives learning.
      METHODS: We administered surveys to residents (n = 35) at three time points to
      determine if and how an OSCE influenced their learning: before and immediately
      following the OSCE, and after the distribution of their results. Differences in
      quantitative responses between high- and low-performing residents and across time
      were compared using repeated-measures ANOVA. Thematic analysis was used to
      analyze narrative comments. RESULTS: Participants' goals for the OSCE related to
      performance, mastery and feedback. Almost all participants reported that they had
      learned something from the OSCE (94%) and most participants generated learning
      goals after the OSCE (71%). High performers appeared to recognize the importance
      of content-related knowledge for scoring well before and after the OSCE, whereas
      low performers may have under-estimated its importance until after the
      examination. DISCUSSION: Participants viewed a formative OSCE as both a hurdle to
      overcome (assessment of learning) and an opportunity to learn (assessment for
      learning). Understanding how OSCEs influence study behavior can help guide the
      development of assessments that promote learning.

PMID- 29037099
TI  - Eosinophilic otitis media diagnosis using flow cytometric immunophenotyping.
AB  - OBJECTIVES: (1) To assess the ability of flow cytometric immunophenotyping to
      detect and quantitate eosinophils in patients with eosinophilic otitis media
      (EOM). (2) to evaluate the association of EOM to bronchial asthma. METHODS:
      Twenty-one patients with chronic otorrhea or middle ear effusion (MEE) were
      included in this prospective cohort study. Group I composed of 10 patients (14
      ears) and associated to bronchial asthma. Group II included 11 patients (11 ears)
      without bronchial asthma. Samples of MEE were sent for flow cytometric analysis
      at initial presentation. Patients with positive eosinophils on flow cytometric
      immunophenotyping were analyzed after one-month course of dexamethasone eardrops.
      RESULTS: EOM was diagnosed in all patients of group I and in three patients of
      group II. The mean eosinophils percentage was 43.5% and 14.2% for group I and
      group II, respectively (p = .006). Those patients showed a significant response
      to dexamethasone eardrops, both on clinical examination and on flow cytometric
      analysis with a decrease in eosinophil levels post-treatment. However, this
      improvement was temporary and symptoms recurred after treatment cessation.
      Bronchial asthma was not associated to all patients with EOM. CONCLUSION:
      Diagnosis of EOM remained mostly clinical; flow cytometry immunophenotyping of
      MEE may be helpful as an additional tool in diagnosis and monitoring the response
      to treatment, particularly in non-asthmatic patients.

PMID- 29037100
TI  - Response from Original Authors - RE: Six novel rare nonsynonymous mutations for
      migraine without aura identified by exome sequencing.

PMID- 29037102
TI  - Complete hydatidiform moles are composed of paternal chromosomes and maternal
      mitochondria.
AB  - Mitochondrial DNA (mtDNA) and genomic DNA are produced in separate subcellular
      compartments. Human mtDNA is transmitted via maternal transmission in general.
      Complete hydatidiform moles (CHMs) represent major trophoblastic diseases that
      are cytogenetically exceptional because the chromosomal genomic DNA is derived
      only from sperm cells, making them strikingly different from normal concepti.
      However, few reports have described the mtDNA-transmission pattern in
      hydatidiform moles. To evaluate mtDNA transmission in androgenetic CHMs, we
      compared the sequences of hypervariable regions in 16 trios sets of mtDNAs from
      maternal, paternal, and villous samples of androgenetic CHMs diagnosed by short
      tandem repeat-polymorphism analysis. All mtDNAs in androgenetic CHMs were
      maternally derived, in line with the general human inheritance pattern. Three
      maternal mtDNAs were heteroplasmic. The heterozygous status of maternal mtDNA was
      reflected in villous tissue, in which variants status was also heterozygous. CHMs
      are composed of paternal chromosomes and maternal mitochondria.

PMID- 29037101
TI  - The potential of solanezumab and gantenerumab to prevent Alzheimer's disease in
      people with inherited mutations that cause its early onset.
AB  - INTRODUCTION: The recent failure of several clinical trials on anti-beta-amyloid
      (Abeta) drugs in Alzheimer's disease (AD) suggested earlier intervention in the
      disease course. Secondary prevention trials have been started in autosomal
      dominant AD (ADAD) individuals without cognitive dysfunction and in cognitively
      healthy subjects at risk of developing sporadic AD (SAD). Areas covered: Herein,
      the authors discuss prevention trials in ADAD and SAD, with a focus on the anti
      Abeta monoclonal antibodies solanezumab and gantenerumab presently in Phase III
      clinical development. These therapies are also being tested in the Dominantly
      Inherited Alzheimer's Network Trials Unit (DIAN-TU). Expert opinion: Anti-Abeta
      monoclonal antibodies are being tested in subjects at the preclinical stage of
      ADAD and even in symptom-free subjects at risk of developing SAD. The subsequent
      DIAN-TU Adaptive Prevention Trial is a 4-year study that will assess whether such
      biomarker effects may stop the progress of the AD process, preventing cognitive
      symptoms. The hope is to interfere in the disease course when it is not too late.
      A clinical success of these prevention trials would represent the proof of the
      Abeta hypothesis of AD.

PMID- 29037103
TI  - Ameliorative effect of myo-inositol on red blood cell alterations in polycystic
      ovary syndrome: in vitro study.
AB  - Polycystic ovary syndrome (PCOS)is a gynecological endocrine disorder which is
      associated with systemic inflammatory status inducing red blood cells (RBC)
      membrane alterations related to insulin resistance and testosterone levels which
      could be greatly improved by myo-inositol (MYO) uptake. In this study we aim to
      evaluate the effect of MYO in reducing oxidative-related alterations through in
      vitro study on PCOS RBC. Blood samples from two groups of volunteers, control
      group (CG, n = 12) and PCOS patient group (PG, n = 12), were analyzed for band 3
      tyrosine phosphorylation (Tyr-P), high molecular weight aggregate (HMWA), IgG in
      RBC membranes, and glutathione (GSH) in cytosol, following O/N incubation in the
      presence or absence of MYO. PCOS RBC underwent oxidative stress as indicated by
      higher band 3 Tyr-P and HMWA and increased membrane bound autologous IgG. Twenty
      four hours (but not shorter time) MYO incubation, significantly improved both Tyr
      P level and HMWA formation and concomitant membrane IgG binding. However, no
      relevant modification of GSH content was detected. PCOS RBC membranes are
      characterized by increased oxidized level and enhanced sensitivity to oxidative
      injuries leading to potential premature RBC removal. MYO treatment is effective
      in reducing oxidative related abnormalities in PCOS patients probably restoring
      the inositol phospholipid pools of the membranes.

PMID- 29037104
TI  - High-magnitude head impact exposure in youth football.
AB  - OBJECTIVE Even in the absence of a clinically diagnosed concussion, research
      suggests that neurocognitive changes may develop in football players as a result
      of frequent head impacts that occur during football games and practices. The
      objectives of this study were to determine the specific situations in which high
      magnitude impacts (accelerations exceeding 40 g) occur in youth football games
      and practices and to assess how representative practice activities are of games
      with regard to high-magnitude head impact exposure. METHODS A total of 45 players
      (mean age 10.7 +/- 1.1 years) on 2 youth teams (Juniors [mean age 9.9 +/- 0.6
      years; mean body mass 38.9 +/- 9.9 kg] and Seniors [mean age 11.9 +/- 0.6 years;
      mean body mass 51.4 +/- 11.8 kg]) wore helmets instrumented with accelerometer
      arrays to record head impact accelerations for all practices and games. Video
      recordings from practices and games were used to verify all high-magnitude head
      impacts, identify specific impact characteristics, and determine the amount of
      time spent in each activity. RESULTS A total of 7590 impacts were recorded, of
      which 571 resulted in high-magnitude head impact accelerations exceeding 40 g
      (8%). Impacts were characterized based on the position played by the team member
      who received the impact, the part of the field where the impact occurred, whether
      the impact occurred during a game or practice play, and the cause of the impact.
      High-magnitude impacts occurred most frequently in the open field in both games
      (59.4%) and practices (67.5%). "Back" position players experienced a greater
      proportion of high-magnitude head impacts than players at other positions. The 2
      teams in this study structured their practice sessions similarly with respect to
      time spent in each drill, but impact rates differed for each drill between the
      teams. CONCLUSIONS High-magnitude head impact exposure in games and practice
      drills was quantified and used as the basis for comparison of exposure in the 2
      settings. In this cohort, game impact rates exceeded those for practice. Back
      players, who were often positioned in the open field, were shown to experience
      elevated levels of head impact exposure relative to players at other positions.
      The analysis also suggests that practice intensity, which may be influenced by
      coaching style, may also affect high-magnitude head impact exposure. Future
      studies should investigate this aspect as a factor affecting head impact
      exposure.

PMID- 29037105
TI  - The role of female obesity on in vitro fertilization outcomes.
AB  - The aim of this review is to analyze the role of obesity on fertility outcome in
      women undergoing in vitro fertilization (IVF) with respect to clinical or live
      birth rates and pregnancy loss rates. Despite findings from several earlier and
      newer studies that obesity does not adversely affect pregnancy outcome in women
      attempting conception, numerous reports from mostly recent studies suggest that
      obesity undoubtedly impairs IVF outcomes. Obesity impairs ovarian responsiveness
      to gonadotrophin stimulation, requiring higher doses of medication, increased
      risk of cycle cancelation, pre-term delivery, low birth weight or miscarriage,
      and decreases implantation, clinical pregnancy or live birth rates compared to
      women of normal weight. The mechanisms underlying the adverse effects of female
      obesity on IVF outcome may be primarily explained by functional alterations to
      the hypothalamic-pituitary-ovarian axis. Additionally, obesity appears to affect
      deleteriously the number and quality of oocytes or embryos, and impairs
      endometrial decidualization which is necessary for uterine receptivity.
      Nevertheless, attaining normal body weight by the use of lifestyle modifications,
      including a healthy diet and exercise over time of several months before and
      during an IVF treatment, may be successful in achievement of gradual and
      sustainable weight loss with improvement of IVF outcome.

PMID- 29037106
TI  - Standard Versus Simplified Consent Materials for Biobank Participation:
      Differences in Patient Knowledge and Trial Accrual.
AB  - Replacing standard consent materials with simplified materials is a promising
      intervention to improve patient comprehension, but there is little evidence on
      its real-world implementation. We employed a sequential two-arm design to compare
      the effect of standard versus simplified consent materials on potential donors'
      understanding of biobank processes and their accrual to an active biobanking
      program. Participants were female patients of a California breast health clinic.
      Subjects from the simplified arm answered more items correctly ( p = .064),
      reported "don't know" for fewer items ( p = .077), and consented to donate to the
      biobank at higher rates ( p = .025) than those from the standard arm. Replacing
      an extant consent form with a simplified version is feasible and may benefit
      patient comprehension and study accrual.

PMID- 29037108
TI  - A workplace intervention program and the increase in HIV knowledge, perceived
      accessibility and use of condoms among young factory workers in Thailand.
AB  - Vulnerability to Human Immunodeficiency Virus (HIV) infection among factory
      workers is a global problem. This study investigated the effectiveness of an
      intervention to increase AIDS knowledge, perceived accessibility to condoms and
      condom use among young factory workers in Thailand. The intervention was a
      workplace program designed to engage the private sector in HIV prevention. A
      cross-sectional survey conducted in 2008 to measure program outcomes in factories
      in Thailand was used in this study. The workplace intervention included the
      development of policies for management of HIV-positive employees, training
      sessions for managers and workers, and distribution of educational materials and
      condoms. A multi-level analysis was used to investigate the effect of HIV/AIDS
      prevention program components at the workplace on HIV/AIDS knowledge, perceived
      accessibility to condoms and condom use with regular sexual partners among 699
      young factory workers (aged 18-24 years), controlling for their individual socio
      demographic characteristics. Interventions related to the management and services
      component including workplace AIDS policy formulation, condom services programs
      and behavioral change campaigns were found to be significantly related to
      increased AIDS knowledge, perceived accessibility to condoms and condom use with
      regular partners. The effect of the HIV/AIDS training for managers, peer leaders
      and workers was positive but not statistically significant. With some revision of
      program components, scaling up of workplace interventions and the engagement of
      the private sector in HIV prevention should be seriously considered.

PMID- 29037109
TI  - The process of co-creating the interface for VENSTER, an interactive artwork for
      nursing home residents with dementia.
AB  - INTRODUCTION: Interactive art installations might engage nursing home residents
      with dementia. The main aim of this article was to describe the challenging
      design process of an interactive artwork for nursing home residents, in co
      creation with all stakeholders and to share the used methods and lessons learned.
      This process is illustrated by the design of the interface of VENSTER as a case.
      METHODS: Nursing home residents from the psychogeriatric ward, informal
      caregivers, client representatives, health care professionals and members of the
      management team were involved in the design process, which consisted of three
      phases: (1) identify requirements, (2) develop a prototype and (3) conduct
      usability tests. Several methods were used (e.g. guided co-creation sessions,
      "Wizard of Oz"). Each phase generated "lessons learned", which were used as the
      departure point of the next phase. RESULTS: Participants hardly paid attention to
      the installation and interface. There, however, seemed to be an untapped
      potential for creating an immersive experience by focussing more on the content
      itself as an interface (e.g. creating specific scenes with cues for interaction,
      scenes based on existing knowledge or prior experiences). "Fifteen lessons
      learned" which can potentially assist the design of an interactive artwork for
      nursing home residents suffering from dementia were derived from the design
      process. CONCLUSIONS: This description provides tools and best practices for
      stakeholders to make (better) informed choices during the creation of interactive
      artworks. It also illustrates how co-design can make the difference between
      designing a pleasurable experience and a meaningful one. Implications for
      rehabilitation Co-design with all stakeholders can make the difference between
      designing a pleasurable experience and a meaningful one. There seems to be an
      untapped potential for creating an immersive experience by focussing more on the
      content itself as an interface (e.g. creating specific scenes with cues for
      interaction, scenes based on existing knowledge or prior experiences). Content as
      an interface proved to be a crucial part of the overall user experience. The case
      study provides tools and best practices (15 "lessons learned") for stakeholders
      to make (better) informed choices during the creation of interactive artworks.

PMID- 29037110
TI  - Reuse of wastewaters on dyeing of polyester fabric with encapsulated disperse
      dye.
AB  - The textile industry can benefit from the use of microcapsules, both adding value
      to products through the production of technical or functional textiles and
      improving the processes in the production chain. Some applications have been
      widely explored in academic research, but many are not feasible for use in
      industrial scale. Thus, the aim of this study was to develop consistent and
      efficient methodologies for the encapsulation of active compounds commonly used
      in the textile industry, employing materials which are viable for large-scale
      application. In this study, polyurethane-urea microcapsules were formulated by
      interfacial polymerization and encapsulated with C.I Disperse Blue 60 for the
      dyeing of polyester fabric without the use of dispersing agents and other
      auxiliaries. The dyeing was carried out in a high temperature dyeing machine with
      a very simple dyebath, in which there are only dissolved dye molecules,
      microencapsulated dyes and the fabric. Additionally, the dyebath wastewaters were
      reused on a further dyeing as 100% bathwater and mixed with 50% distilled water.
      Colorimetric measurements show excellent colour removal in both samples.

PMID- 29037107
TI  - First-in-Man Evaluation of 124I-PGN650: A PET Tracer for Detecting
      Phosphatidylserine as a Biomarker of the Solid Tumor Microenvironment.
AB  - PURPOSE: PGN650 is a F(ab')2 antibody fragment that targets phosphatidylserine
      (PS), a marker normally absent that becomes exposed on tumor cells and tumor
      vasculature in response to oxidative stress and increases in response to therapy.
      PGN650 was labeled with 124I to create a positron emission tomography (PET) agent
      as an in vivo biomarker for tumor microenvironment and response to therapy. In
      this phase 0 study, we evaluated the pharmacokinetics, safety, radiation
      dosimetry, and tumor targeting of this tracer in a cohort of patients with
      cancer. METHODS: Eleven patients with known solid tumors received approximately
      140 MBq (3.8 mCi) 124I-PGN650 intravenously and underwent positron emission
      tomography-computed tomography (PET/CT) approximately 1 hour, 3 hours, and either
      24 hours or 48 hours later to establish tracer kinetics for the purpose of
      calculating radiation dosimetry (from integration of the organ time-activity
      curves and OLINDA/EXM using the adult male and female models). RESULTS: Known
      tumor foci demonstrated mildly increased uptake, with the highest activity at the
      latest imaging time. There were no unexpected adverse events. The liver was the
      organ receiving the highest radiation dose (0.77 mGy/MBq); the effective dose was
      0.41 mSv/MBq. CONCLUSION: Although 124I-PGN650 is safe for human PET imaging, the
      tumor targeting with this agent in patients was less than previously observed in
      animal studies.

PMID- 29037111
TI  - Head and neck size and neck strength predict linear and rotational acceleration
      during purposeful soccer heading.
AB  - There is increasing societal concern about the long-term effects of repeated
      impacts from soccer heading, but there is little information about ways to reduce
      head impact severity. The purpose of this study was to identify factors that
      contribute to head acceleration during soccer heading. One-hundred soccer players
      completed 12 controlled soccer headers. Peak linear (PLA) and rotational (PRA)
      accelerations were measured using a triaxial accelerometer and gyroscope. Head
      acceleration contributing factors were grouped into 3 categories: size (head
      mass, neck girth), strength (sternocleidomastoid, upper trapezius) and technique
      [kinematics (trunk, head-to-trunk range-of-motion), sternocleidomastoid and upper
      trapezius activity]. Multiple regression analyses indicated size variables
      explained 22.1% of the variance in PLA and 23.3% of the variance in PRA; strength
      variables explained 13.3% of the variance in PLA and 17.2% of the variance in
      PRA; technique variables did not significantly predict PLA or PRA. These findings
      suggest that head and neck size and neck strength predict PLA and PRA.
      Anthropometric and neck strength measurements should be considered when
      determining an athlete's readiness to begin soccer heading.

PMID- 29037112
TI  - Peer-led, transformative learning approaches increase classroom engagement in
      care self-management classes during inpatient rehabilitation of individuals with
      spinal cord injury.
AB  - OBJECTIVE: Evaluate effects of revised education classes on classroom engagement
      during inpatient rehabilitation for individuals with spinal cord injury/disease
      (SCI/D). DESIGN: Multiple-baseline, quasi-experimental design with video recorded
      engagement observations during conventional and revised education classes; visual
      and statistical analysis of difference in positive engagement responses observed
      in classes using each approach. PARTICIPANTS/SETTING: 81 patients (72% male, 73%
      white, mean age 36 SD 15.6) admitted for SCI/D inpatient rehabilitation in a non
      profit rehabilitation hospital, who attended one or more of 33 care self
      management education classes that were video recorded. All study activities were
      approved by the host facility institutional review board. INTERVENTION:
      Conventional nurse-led self-management classes were replaced with revised peer
      led classes incorporating approaches to promote transformative learning. Revised
      classes were introduced across three subject areas in a step-wise fashion over 15
      weeks. OUTCOME MEASURE: Positive engagement responses (asking questions,
      participating in discussion, gesturing, raising hand, or otherwise noting
      approval) were documented from video recordings of 14 conventional and 19 revised
      education classes. RESULTS: Significantly higher average (per patient per class)
      positive engagement responses were observed in the revised compared to
      conventional classes (p=0.008). CONCLUSION: Redesigning SCI inpatient
      rehabilitation care self-management classes to promote transformative learning
      increased patient engagement. Additional research is needed to examine longer
      term outcomes and replicability in other settings.

PMID- 29037113
TI  - Temporomandibular joint MR images: Incidental head and neck findings and
      pathologies.
AB  - OBJECTIVE: To report the number and frequency of incidental findings (IFs)
      detected during magnetic resonance (MR) imaging screening of the
      temporomandibular joint (TMJ) and to define related diseases. METHODS: Bilateral
      TMJ MR images in the sagittal and coronal sections, from 518 patients with TMJ
      symptoms were evaluated retrospectively. Patients who were diagnosed with IFs
      were sent for consultation and clarification of the findings. Patient age,
      gender, IFs, locations, and diseases were classified and noted.  Results: Seventy
      eight (15%) patients were diagnosed with 117 IFs. Of them, 43 were diagnosed with
      a single IF, and 35 were diagnosed with more than one IF. The most frequent
      locations were paranasal sinuses and mastoid air cells. The most frequent
      diseases were inflammatory and cystic lesions.  Discussion: While examining TMJ
      MR images, it is important to check for evidence of IFs or pathologies that may
      have mimicked signs and symptoms of TMJ disorders.

PMID- 29037114
TI  - Home-based hand rehabilitation with a robotic glove in hemiplegic patients after
      stroke: a pilot feasibility study.
AB  - OBJECTIVE: To evaluate the feasibility and safety of home rehabilitation of the
      hand using a robotic glove, and, in addition, its effectiveness, in hemiplegic
      patients after stroke. METHODS: In this non-randomized pilot study, 21 hemiplegic
      stroke patients (Ashworth spasticity index <= 3) were prescribed, after in
      hospital rehabilitation, a 2-month home-program of intensive hand training using
      the Gloreha Lite glove that provides computer-controlled passive mobilization of
      the fingers. Feasibility was measured by: number of patients who completed the
      home-program, minutes of exercise and number of sessions/patient performed.
      Safety was assessed by: hand pain with a visual analog scale (VAS), Ashworth
      spasticity index for finger flexors, opponents of the thumb and wrist flexors,
      and hand edema (circumference of forearm, wrist and fingers), measured at start
      (T0) and end (T1) of rehabilitation. Hand motor function (Motricity Index, MI),
      fine manual dexterity (Nine Hole Peg Test, NHPT) and strength (Grip test) were
      also measured at T0 and T1. RESULTS: Patients performed, over a mean period 56
      (49-63) days, a total of 1699 (1353-2045) min/patient of exercise with Gloreha
      Lite, 5.1 (4.3-5.8) days/week. Seventeen patients (81%) completed the full
      program. The mean VAS score of hand pain, Ashworth spasticity index and hand
      edema did not change significantly at T1 compared to T0. The MI, NHPT and Grip
      test improved significantly (p = 0.0020, 0.0156 and 0.0024, respectively)
      compared to baseline. CONCLUSION: Gloreha Lite is feasible and safe for use in
      home rehabilitation. The efficacy data show a therapeutic effect which need to be
      confirmed by a randomized controlled study.

PMID- 29037115
TI  - Low subjective social status in the police is linked to health-relevant changes
      in diurnal salivary alpha-amylase activity in Swiss police officers.
AB  - The objective of this study was to assess basal autonomic nervous system (ANS)
      activity as a pathway linking subjective social status to health in a high-demand
      work environment. It was hypothesized that officers with a lower status
      experienced more chronic stress (higher basal ANS activity) and that chronic
      stress was related to more health problems. Fifty-six male and female Swiss
      police officers self-reported on subjective social status (country, community,
      friends, police) and their health (depression, post-traumatic stress, physical
      symptoms) and collected 12 saliva samples over two days for basal alpha-amylase
      activation (sAA) assessment. Multilevel regression analyses revealed that
      subjective social status in the police and physical symptoms explained a
      significant part of the variance in diurnal sAA activity patterns. The current
      findings support the idea that more narrowly defined subjective social status may
      be more closely linked to biological stress mechanisms. Additionally, sAA
      activity was specifically related to physical, but not mental health problems.
      These results suggest that subjective social status referencing one's work
      environment may be a promising early indicator of health-relevant changes in
      stress-related physiological systems.

PMID- 29037116
TI  - Relating physicochemical properties of alginate-HMP complexes to their
      performance as drug delivery systems.
AB  - This study aims to analyze the effect of physicochemical properties of alginate
      high methoxyl pectin (HMP) complexes on their performance as drug delivery
      systems. Rheology, textural properties and swelling behavior of alginate-HMP
      complexes were determined. HMP alone showed weak gelling ability. As ratio of
      alginate increased, gel capability, hardness and adhesiveness of gels increased,
      but swelling rate decreased. Bovine serum albumin (BSA) was used as a model drug
      and entrapped in the alginate-HMP beads. Morphology of beads was correlated with
      adhesiveness. Drug loading content and encapsulation efficiency were related to
      electrostatic interactions between BSA and alginate-HMP complexes. Drug release
      profiles were correlated with both texture and swelling properties of alginate
      HMP complexes and morphology of beads in simulated gastric fluids, while release
      in simulated intestinal fluids was affected by drug loading content. This study
      gives enlightenment that pre-selection of encapsulation materials may be achieved
      prior to encapsulation based on physicochemical properties of materials.

PMID- 29037117
TI  - Sialic Acid-Binding Immunoglobulin-Like Lectin1 as a Novel Predictive Biomarker
      for Relapse in Graves' Disease: A Multicenter Study.
AB  - BACKGROUND: There are currently no reliable biomarkers to predict relapse in
      Graves' disease (GD). In the present study, we investigated novel diagnostic
      biomarkers to predict the long-term remission of or relapse in GD. METHODS: A DNA
      microarray analysis was performed to examine gene expression in the peripheral
      leukocytes of a frequently relapsing patient with GD and a patient in long-term
      remission after the discontinuation of antithyroid drugs (ATDs). Based on the DNA
      microarray analysis, we focused on Sialic acid-binding immunoglobulin-like
      lectin1 (SIGLEC1) as a candidate novel biomarker to predict GD relapse. Three
      hundred and fifty-eight patients with GD in the thyroid clinics of four different
      hospitals in Japan were included in a cross-sectional study to establish whether
      SIGLEC1 mRNA levels distinguish GD relapse experience from long-term remission.
      An additional 55 patients with GD were enrolled in a prospective study to clarify
      whether SIGLEC1 mRNA levels at ATD discontinuation predict GD relapse. RESULTS:
      SIGLEC1 mRNA levels were significantly higher in patients with GD relapse
      experience than in those in long-term remission. Based on the receiver operating
      characteristic analysis, we found that high SIGLEC1 mRNA levels (>=258.9 copies)
      significantly distinguished GD relapse experience from long-term remission (p <
      0.0001; sensitivity 66.7%, specificity 70.1%). In the prospective study, when the
      optimal cutoff value from the receiver operating characteristic curve analysis
      was applied to SIGLEC1 mRNA positivity at ATD discontinuation, SIGLEC1-positive
      patients (>=258.9 copies) showed a significantly higher cumulative risk of
      relapse than SIGLEC1-negative patients (<258.9 copies) (p = 0.022, the log-rank
      test). CONCLUSIONS: SIGLEC1 mRNA levels have potential as a novel predictive
      biomarker for GD relapse.

PMID- 29037118
TI  - Pre-season dietary intake of professional soccer players.
AB  - BACKGROUND: Despite the well-documented importance of nutrition in optimizing
      performance and health, the dietary intake of soccer players has attracted little
      attention. AIM: We aimed to assess the pre-season dietary intake of professional
      soccer players and its adequacy in macro and micronutrients. METHODS: The pre
      season dietary intake of 19 male athletes was assessed using a semi-structured 3
      day food record. To determine dietary adequacy and excess, energy and
      macronutrient intake were compared with the Brazilian dietary reference values
      for athletes, and micronutrients were compared with the Estimated Average
      Requirement - EAR (minimum recommendation) and Tolerable Upper Intake Level - UL
      (maximum recommendation). RESULTS: Mean daily energy intake (40.74+/-12.81
      kcal/kg) was adequate. However, there was a low carbohydrate intake (5.44+/-1.86
      g/kg/day) and a high amount of protein and fat (1.91+/-0.75 and 1.27+/-0.50
      g/kg/day, respectively). Sodium intake (3141.77+/-939.76 mg/day) was higher than
      UL (2300 mg/day), while the majority of players showed daily intake of vitamin A
      (74%), vitamin D (100%), folate (58%), calcium and magnesium (68%) below the EAR
      (625, 10 and 320 ug/day, 800 and 330 mg/day, respectively). CONCLUSION: The
      dietary intake of professional soccer players was adequate in energy, but
      inadequate in macro and micronutrients, which suggests the need to improve
      nutritional practices to sustain the physical demands of soccer during pre
      season.

PMID- 29037119
TI  - A qualitative study of new graduates' readiness to use nursing informatics in
      acute care settings: clinical nurse educators' perspectives.
AB  - BACKGROUND: There is an increase in demand for newly graduated nurses who are
      ready to use nursing informatics (NI) efficiently in technology-rich healthcare
      environments. However, the progress of embedding NI into curricula has been slow
      worldwide, and literature reports graduates are not ready to use NI tools
      effectively in the workplace, posing potential threats to patient safety. In the
      absence of National Standards for NI competencies, graduates' NI needs on
      entering the workplace need to be explored. AIM: To identify graduates' NI needs
      on entering the workplace in acute care settings from the perspectives of
      clinical nurse educators. METHODS: A qualitative study using interpretive
      description with one focus group of six clinical nurse educators was conducted.
      Clinical nurse educators who are significantly involved in supporting graduates
      from their first day in the workplace were purposively recruited. The focus group
      was audiotaped, transcribed verbatim and analysed using thematic analysis.
      RESULTS: Graduates were found to be inadequately prepared to use NI tools on
      entering the workplace. Inefficient hospital systems and a ward culture that was
      discouraging graduates' NI practice were identified as major barriers to the
      implementation of NI practice. Lack of exposure to specific hospital systems as
      undergraduates was also identified as a significant barrier to NI practice among
      graduates. CONCLUSIONS: As well as supporting the pre-existing studies on NI
      skills in graduates and barriers to graduates' NI practice, this current study
      identified the need for nursing schools to further integrate NI into formal
      curricula and increased opportunity for exposure to hospital systems as
      undergraduates. Further studies in multiple settings across Australia are
      recommended to ensure the transferability of the findings of this study.

PMID- 29037120
TI  - Test anxiety and self-esteem in senior high school students: a cross-sectional
      study.
AB  - PURPOSE: In this study, it is aimed to determine the level of test anxiety and
      self-esteem in the high school students preparing for the university exam in
      Bitlis, Turkey, and to investigate the effect of test anxiety on self-esteem.
      MATERIAL AND METHODS: Seven-hundred and twenty-four high school students who were
      preparing for the university entrance examination in Bitlis participated in the
      study. A questionnaire which includes socio-demographic data form, Rosenberg Self
      Esteem Scale and Revised Test Anxiety Scale was prepared as an e-questionnaire
      for the students to fill easily and uploaded to the Bitlis State Hospital's
      website. Schools were called and informed for the students to fill out the e
      questionnaire on the Internet. RESULTS: The most important findings from our
      study are that gender is influential on test anxiety and self-esteem score and
      test anxiety level are negatively correlated. It was observed that female
      students had more test anxiety than male students and those who had higher self
      esteem had less test anxiety. CONCLUSION: Consequently, our study shows that
      university entrance examination creates anxiety on students and reduces self
      esteem, especially in female students.

PMID- 29037121
TI  - Predicting Injury Severity and Neurological Recovery after Acute Cervical Spinal
      Cord Injury: A Comparison of Cerebrospinal Fluid and Magnetic Resonance Imaging
      Biomarkers.
AB  - Biomarkers of acute human spinal cord injury (SCI) could provide a more objective
      measure of spinal cord damage and a better predictor of neurological outcome than
      current standardized neurological assessments. In SCI, there is growing interest
      in establishing biomarkers from cerebrospinal fluid (CSF) and from magnetic
      resonance imaging (MRI). Here, we compared the ability of CSF and MRI biomarkers
      to classify injury severity and predict neurological recovery in a cohort of
      acute cervical SCI patients. CSF samples and MRI scans from 36 acute cervical SCI
      patients were examined. From the CSF samples taken 24 h post-injury, the
      concentrations of inflammatory cytokines (interleukin [IL]-6, IL-8, monocyte
      chemotactic protein-1), and structural proteins (tau, glial fibrillary acidic
      protein, and S100beta) were measured. From the pre-operative MRI scans, we
      measured intramedullary lesion length, hematoma length, hematoma extent, CSF
      effacement, cord expansion, and maximal spinal cord compression. Baseline and 6
      month post-injury assessments of American Spine Injury Association Impairment
      Scale (AIS) grade and motor score were conducted. Both MRI measures and CSF
      biomarker levels were found to correlate with baseline injury grade, and in
      combination they provided a stronger model for classifying baseline AIS grade
      than CSF or MRI biomarkers alone. For predicting neurological recovery, the
      inflammatory CSF biomarkers best predicted AIS grade conversion, whereas
      structural biomarker levels best predicted motor score improvement. A logistic
      regression model utilizing CSF biomarkers alone had a 91.2% accuracy at
      predicting AIS conversion, and was not strengthened by adding MRI features or
      even knowledge of the baseline AIS grade. In a direct comparison of MRI and CSF
      biomarkers, the CSF biomarkers discriminate better between different injury
      severities, and are stronger predictors of neurological recovery in terms of AIS
      grade and motor score improvement. These findings demonstrate the utility of
      measuring the acute biological responses to SCI as biomarkers of injury severity
      and neurological prognosis.

PMID- 29037122
TI  - Obtaining edaphic biostimulants/biofertilizers from sewage sludge using
      fermentative processes. Short-time effects on soil biochemical properties.
AB  - In this manuscript, we study the manufacture and effect on soils of different
      edaphic biostimulants/biofertilizers (BS) obtained from sewage sludge using
      Bacillus licheniformis as biological tool. These BS consist of different
      combinations of organic matter, bacteria and enzymes that were subjected to
      several treatments. These BS were applied in soil in order to observe their
      influence on the biochemical properties (enzymatic activities and ergosterol
      content). Dehydrogenase, urease, beta-glucosidase, phosphatase activities and
      ergosterol content were measured at different incubation days. Only dehydrogenase
      activity and ergosterol content were significantly stimulated after the
      application of BS1 and BS4. Rest of the extracellular activities were not
      stimulated probably because B. licheniformis practically has digested all organic
      substrates during fermentation process.

PMID- 29037124
TI  - Effects of different wastewater characteristics and treatment techniques on the
      bacterial community structure in three pharmaceutical wastewater treatment
      systems.
AB  - Pharmaceutical wastewater is a typical type of wastewater with high
      concentrations of organic pollutants, but research on this subject is limited.
      The aeration tanks of three different pharmaceutical wastewater treatment systems
      were seeded with the same inocula and stably operated for 40 days. Then, aerobic
      sludge samples from the three aeration tanks were collected to provide insight
      into the bacterial community composition of the activated sludges. Additionally,
      we investigated the effects of wastewater characteristics and the type and
      operation of the technological system on the microbial communities. High
      throughput sequencing analysis demonstrated that the communities enriched in the
      three reactors had differing. The dominant phyla detected were Proteobacteria,
      Chloroflexi, Bacteroidetes and candidate division TM7, while the dominant clones
      were uncultured Candidatus Saccharibacteria bacterium, uncultured Saprospiraceae
      bacterium, PHOS-HE51(AF314433.1), uncultured Anaerolineaceae bacterium and
      Blastocatella, suggesting their importance in pharmaceutical wastewater treatment
      plants. According to the wastewater parameters and canonical correspondence
      analyses, we can conclude that uncultured Candidatus Saccharibacteria bacterium,
      uncultured Anaerolineaceae bacterium and Blastocatella contribute to ammonium
      nitrogen ([Formula: see text]) removal; uncultured Saprospiraceae bacterium plays
      an important role in treating nitrogen; and chemical oxygen demand and PHOS-HE51
      contribute to total phosphorus removal.

PMID- 29037123
TI  - Ultrafine Particle Exposure Reveals the Importance of FOXO1/Notch Activation
      Complex for Vascular Regeneration.
AB  - AIMS: Redox active ultrafine particles (UFP, d < 0.2 MUm) promote vascular
      oxidative stress and atherosclerosis. Notch signaling is intimately involved in
      vascular homeostasis, in which forkhead box O1 (FOXO1) acts as a co-activator of
      the Notch activation complex. We elucidated the importance of FOXO1/Notch
      transcriptional activation complex to restore vascular regeneration after UFP
      exposure. RESULTS: In a zebrafish model of tail injury and repair, transgenic
      Tg(fli1:GFP) embryos developed vascular regeneration at 3 days post amputation
      (dpa), whereas UFP exposure impaired regeneration (p < 0.05, n = 20 for control,
      n = 28 for UFP). UFP dose dependently reduced Notch reporter activity and Notch
      signaling-related genes (Dll4, JAG1, JAG2, Notch1b, Hey2, Hes1; p < 0.05, n = 3).
      In the transgenic Tg(tp1:GFP; flk1:mCherry) embryos, UFP attenuated endothelial
      Notch activity at the amputation site (p < 0.05 vs. wild type [WT], n = 20). A
      disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) inhibitor
      or dominant negative (DN)-Notch1b messenger RNA (mRNA) disrupted the vascular
      network, whereas notch intracellular cytoplasmic domain (NICD) mRNA restored the
      vascular network (p < 0.05 vs. WT, n = 20). UFP reduced FOXO1 expression, but not
      Master-mind like 1 (MAML1) or NICD (p < 0.05, n = 3). Immunoprecipitation and
      immunofluorescence demonstrated that UFP attenuated FOXO1-mediated NICD pull-down
      and FOXO1/NICD co-localization, respectively (p < 0.05, n = 3). Although FOXO1
      morpholino oligonucleotides (MOs) attenuated Notch activity, FOXO1 mRNA reversed
      UFP-mediated reduction in Notch activity to restore vascular regeneration and
      blood flow (p < 0.05 vs. WT, n = 5). Innovation and Conclusion: Our findings
      indicate the importance of the FOXO1/Notch activation complex to restore vascular
      regeneration after exposure to the redox active UFP. Antioxid. Redox Signal. 28,
      1209-1223.

PMID- 29037125
TI  - Signature of genetic associations in oral cancer.
AB  - Oral cancer etiology is complex and controlled by multi-factorial events
      including genetic events. Candidate gene studies, genome-wide association
      studies, and next-generation sequencing identified various chromosomal loci to be
      associated with oral cancer. There is no available review that could give us the
      comprehensive picture of genetic loci identified to be associated with oral
      cancer by candidate gene studies-based, genome-wide association studies-based,
      and next-generation sequencing-based approaches. A systematic literature search
      was performed in the PubMed database to identify the loci associated with oral
      cancer by exclusive candidate gene studies-based, genome-wide association studies
      based, and next-generation sequencing-based study approaches. The information of
      loci associated with oral cancer is made online through the resource "ORNATE."
      Next, screening of the loci validated by candidate gene studies and next
      generation sequencing approach or by two independent studies within candidate
      gene studies or next-generation sequencing approaches were performed. A total of
      264 loci were identified to be associated with oral cancer by candidate gene
      studies, genome-wide association studies, and next-generation sequencing
      approaches. In total, 28 loci, that is, 14q32.33 (AKT1), 5q22.2 (APC), 11q22.3
      (ATM), 2q33.1 (CASP8), 11q13.3 (CCND1), 16q22.1 (CDH1), 9p21.3 (CDKN2A), 1q31.1
      (COX-2), 7p11.2 (EGFR), 22q13.2 (EP300), 4q35.2 (FAT1), 4q31.3 (FBXW7), 4p16.3
      (FGFR3), 1p13.3 (GSTM1-GSTT1), 11q13.2 (GSTP1), 11p15.5 (H-RAS), 3p25.3 (hOGG1),
      1q32.1 (IL-10), 4q13.3 (IL-8), 12p12.1 (KRAS), 12q15 (MDM2), 12q13.12 (MLL2),
      9q34.3 (NOTCH1), 17p13.1 (p53), 3q26.32 (PIK3CA), 10q23.31 (PTEN), 13q14.2 (RB1),
      and 5q14.2 (XRCC4), were validated to be associated with oral cancer. "ORNATE"
      gives a snapshot of genetic loci associated with oral cancer. All 28 loci were
      validated to be linked to oral cancer for which further fine-mapping followed by
      gene-by-gene and gene-environment interaction studies is needed to confirm their
      involvement in modifying oral cancer.

PMID- 29037126
TI  - DACT1 overexpression inhibits proliferation, enhances apoptosis, and increases
      daunorubicin chemosensitivity in KG-1alpha cells.
AB  - DACT1 has been shown to participate in the development of many types of tumors;
      however, its role and precise molecular mechanisms in leukemia are unclear. In
      this study, we investigated the effect of DACT1 on KG-1alpha leukemia cells to
      further understand the mechanisms of DACT1-mediated tumor suppression. We
      transfected a DACT1 expression plasmid to upregulate DACT1 in KG-1alpha cells and
      analyzed the resulting phenotypic changes. The results demonstrated that DACT1
      overexpression inhibited KG-1alpha proliferation, increased apoptosis, and
      arrested cells in the G0/G1 phase. Mechanistically, DACT1 overexpression
      inhibited Wnt/beta-catenin signaling by reducing nuclear beta-catenin levels in
      KG-1alpha cells. Furthermore, the viability of KG-1alpha cells transfected with
      DACT1 was significantly reduced when treated with daunorubicin. We also found
      that DACT1 reduced P-glycoprotein expression in KG-1alpha cells. These findings
      revealed an inhibitory role for DACT1 in leukemogenesis and provided evidence
      that DACT1 is an attractive target for the development of novel anti-leukemia
      therapies.

PMID- 29037127
TI  - Role of molecular markers to predict distant metastasis in papillary thyroid
      carcinoma: Promising value of TERT promoter mutations and insignificant role of
      BRAF mutations-a meta-analysis.
AB  - The presence of distant metastasis is associated with an adverse outcome in
      papillary thyroid cancer. We performed a meta-analysis to investigate the role of
      molecular markers as predictors for distant metastasis in papillary thyroid
      cancer. Four electronic databases including PubMed, Web of Science, Scopus, and
      Virtual Health Library were searched, and odds ratio and its 95% confidence
      interval concerning the association of BRAF, RAS, and TERT promoter mutations and
      RET/PTC rearrangements with distant metastasis were calculated using random
      effects model. In total, 42 studies with 11,109 papillary thyroid cancers were
      included for meta-analyses. Overall, the presence of TERT promoter (odds ratio =
      5.95; 95% confidence interval = 2.95-11.99), RAS mutations (odds ratio = 2.5; 95%
      confidence interval = 1.00-6.22), and RET/PTC rearrangements (odds ratio = 1.92;
      95% confidence interval = 1.03-3.56) were found to be associated with a
      significantly increased risk for distant metastasis. BRAF mutations were not
      associated with an elevated risk for distant metastasis (odds ratio = 0.79; 95%
      confidence interval = 0.54-1.16). In conclusion, our study demonstrated the
      promising value of few molecular biomarkers, especially TERT promoter mutations
      in predicting distant metastasis in papillary thyroid cancers, while BRAF
      mutations showed no association with distant metastasis. Our study affirms the
      value of selected mutations for tumor risk stratification and assessment of
      patients' prognosis.

PMID- 29037128
TI  - Predictive value of secondary signs of obstruction in follow-up computed
      tomography of ureteral stones: a study with dynamic computed tomography.
AB  - OBJECTIVES: This study aimed to determine the ratio of obstruction and predictive
      values of secondary signs in follow-up computed tomography (CT) of
      ureterolithiasis patients; to correlate stone characteristics with obstruction;
      to compare enhancement of obstructed and non-obstructed kidneys; and to compare
      radiation dose of the dynamic CT protocol to an excretory-phase protocol.
      MATERIALS AND METHODS: This retrospective study assessed 49 follow-up CT scans of
      patients with remaining ureterolithiasis after a renal colic episode. Obstruction
      was measured as time taken to excretion of contrast medium in dynamic CT. Degree
      of secondary signs of obstruction was evaluated from the unenhanced CT. Data were
      collected on patients' gender and age, stone size and location, time from renal
      colic to follow-up, attenuation of the renal cortex and radiation dose. RESULTS:
      Obstruction was present in 28% (n = 14) at follow-up. Predictive values
      (sensitivity, specificity, positive predictive value, negative predictive value)
      were calculated for hydronephrosis (1.0, 0.63, 0.52, 1.0), hydroureter (1.0, 0.4,
      0.4, 1.0), perirenal stranding (0.21, 0.94, 0.6, 0.75), Gerota's fascia (0.21,
      0.97, 0.75, 0.76) and renal swelling (0.21, 0.97, 0.75, 0.76). Obstruction was
      not correlated with stone characteristics. Enhancement was lower in obstructed
      kidneys (p < 0.01). Radiation dose was reduced by 43% (1.8 mSv). CONCLUSIONS:
      Obstruction was found in 28% of patients. Secondary signs were scarce and of
      indeterminate value to the diagnosis of obstruction. The absence of
      hydronephrosis and hydroureter contradicted obstruction. Stone characteristics
      were not correlated with obstruction. Enhancement of the renal cortex was lower
      in obstructed kidneys. The dynamic protocol reduced the radiation dose.

PMID- 29037129
TI  - Enzymes Regulated via Cystathionine beta-Synthase Domains.
AB  - Cystathionine beta-synthase (CBS) domains discovered 20 years ago can bind
      different adenosine derivatives (AMP, ADP, ATP, S-adenosylmethionine, NAD,
      diadenosine polyphosphates) and thus regulate the activities of numerous
      proteins. Mutations in CBS domains of enzymes and membrane transporters are
      associated with several hereditary diseases. The regulatory unit is a quartet of
      CBS domains that belong to one or two polypeptides and usually form a conserved
      disk-like structure. CBS domains function as "internal inhibitors" in enzymes,
      and their bound ligands either amplify or attenuate the inhibitory effect. Recent
      studies have opened a way to understanding the structural basis of enzyme
      regulation via CBS domains and widened the list of their bound ligands.

PMID- 29037130
TI  - Molecular and Cellular Mechanisms of Sporadic Alzheimer's Disease: Studies on
      Rodent Models in vivo.
AB  - In this review, recent data are presented on molecular and cellular mechanisms of
      pathogenesis of the most widespread (about 95%) sporadic forms of Alzheimer's
      disease obtained on in vivo rodent models. Although none of the available models
      can fully reproduce the human disease, several key molecular mechanisms (such as
      dysfunction of neurotransmitter systems, especially of the acetylcholinergic
      system, beta-amyloid toxicity, oxidative stress, neuroinflammation, mitochondrial
      dysfunction, disturbances in neurotrophic systems) are confirmed with different
      models. Injection models, olfactory bulbectomy, and senescence accelerated OXYS
      rats are reviewed in detail. These three approaches to in vivo modeling of
      sporadic Alzheimer's disease have demonstrated a considerable similarity in
      molecular and cellular mechanisms of pathology development. Studies on these
      models provide complementary data, and each model possesses its specific
      advantages. A general analysis of the data reported for the three models provides
      a multifaceted and the currently most complete molecular picture of sporadic
      Alzheimer's disease. This is highly relevant also from the practical viewpoint
      because it creates a basis for elaboration and preclinical studies of means for
      treatment of this disease.

PMID- 29037131
TI  - Gene Regulation and Signal Transduction in the ICE-CBF-COR Signaling Pathway
      during Cold Stress in Plants.
AB  - Low temperature is an abiotic stress that adversely affects the growth and
      production of plants. Resistance and adaptation of plants to cold stress is
      dependent upon the activation of molecular networks and pathways involved in
      signal transduction and the regulation of cold-stress related genes. Because it
      has numerous and complex genes, regulation factors, and pathways, research on the
      ICE-CBF-COR signaling pathway is the most studied and detailed, which is thought
      to be rather important for cold resistance of plants. In this review, we focus on
      the function of each member, interrelation among members, and the influence of
      manipulators and repressors in the ICE-CBF-COR pathway. In addition, regulation
      and signal transduction concerning plant hormones, circadian clock, and light are
      discussed. The studies presented provide a detailed picture of the ICE-CBF-COR
      pathway.

PMID- 29037133
TI  - Crystal Structure of Wild-Type Centrin 1 from Mus musculus Occupied by Ca2.
AB  - Mus musculus centrin 1 (MmCen1) is located at the cilium of photoreceptor cells
      connecting the outer segment through signal transduction components to the
      metabolically active inner segment. In the cilium, MmCen1 is involved in the
      translocation of transducin between compartments as a result of photoreceptor
      activation. In this study, we report the crystal structure of wild-type MmCen1
      and its Ca2+-binding properties using structure-based mutagenesis. The crystal
      structure exhibits three structural features, i.e. four Ca2+ equally occupied at
      each EF-hand motif, structural changes accompanying helix motion at the N- and C
      lobes, and adoption of N-C type dimerization when Ca2+ binds to EF-hand I and II
      in the N-lobe. The presence of MmCen1 dimers was confirmed in solution by native
      PAGE. Isothermal titration calorimetry data showed sequential binding of Ca2+ at
      four independent sites. Mutations S45A and D49A in EF-hand I alone disrupted the
      Ca2+-binding property of the wild-type protein. Based on the crystal structure of
      MmCen1, we suggest that a dimerization mode between the N- and C-lobes may be
      required by Ca2+ binding at the N-lobe.

PMID- 29037132
TI  - Expression of Hormonal Carcinogenesis Genes and Related Regulatory microRNAs in
      Uterus and Ovaries of DDT-Treated Female Rats.
AB  - The insecticide dichlorodiphenyltrichloroethane (DDT) is a nonmutagenic
      xenobiotic compound able to exert estrogen-like effects resulting in activation
      of estrogen receptor-alpha (ERalpha) followed by changed expression of its
      downstream target genes. In addition, studies performed over recent years suggest
      that DDT may also influence expression of microRNAs. However, an impact of DDT on
      expression of ER, microRNAs, and related target genes has not been fully
      elucidated. Here, using real-time PCR, we assessed changes in expression of key
      genes involved in hormonal carcinogenesis as well as potentially related
      regulatory oncogenic/tumor suppressor microRNAs and their target genes in the
      uterus and ovaries of female Wistar rats during single and chronic multiple-dose
      DDT exposure. We found that applying DDT results in altered expression of
      microRNAs-221, -222, -205, -126a, and -429, their target genes (Pten, Dicer1), as
      well as genes involved in hormonal carcinogenesis (Esr1, Pgr, Ccnd1, Cyp19a1).
      Notably, Cyp19a1 expression seems to be also regulated by microRNAs-221, -222,
      and -205. The data suggest that epigenetic effects induced by DDT as a potential
      carcinogen may be based on at least two mechanisms: (i) activation of ERalpha
      followed by altered expression of the target genes encoding receptor Pgr and
      Ccnd1 as well as impaired expression of Cyp19a1, affecting, thereby, cell hormone
      balance; and (ii) changed expression of microRNAs resulting in impaired
      expression of related target genes including reduced level of Cyp19a1 mRNA.

PMID- 29037134
TI  - Effect of Cyanide on Mitochondrial Membrane Depolarization Induced by Uncouplers.
AB  - In this work, it was found that the ability of common uncouplers - carbonyl
      cyanide p-trifluoromethoxyphenylhydrazone (FCCP) and 2,4-dinitrophenol (DNP) - to
      reduce membrane potential of isolated rat liver mitochondria was diminished in
      the presence of millimolar concentrations of the known cytochrome c oxidase
      inhibitor - cyanide. In the experiments, mitochondria were energized by addition
      of ATP in the presence of rotenone, inhibiting oxidation of endogenous substrates
      via respiratory complex I. Cyanide also reduced the uncoupling effect of FCCP and
      DNP on mitochondria energized by succinate in the presence of ferricyanide.
      Importantly, cyanide did not alter the protonophoric activity of FCCP and DNP in
      artificial bilayer lipid membranes. The causes of the effect of cyanide on the
      efficiency of protonophoric uncouplers in mitochondria are considered in the
      framework of the suggestion that conformational changes of membrane proteins
      could affect the state of lipids in their vicinity. In particular, changes in
      local microviscosity and vacuum permittivity could change the efficiency of
      protonophore-mediated translocation.

PMID- 29037135
TI  - Distinct Mechanisms of Phenotypic Effects of Inactivation and Prionization of
      Swi1 Protein in Saccharomyces cerevisiae.
AB  - Prions are proteins that under the same conditions can exist in two or more
      conformations, and at least one of the conformations has infectious properties.
      The prionization of a protein is typically accompanied by its functional
      inactivation due to sequestration of monomers by the prion aggregates. The most
      of prions has been identified in the yeast Saccharomyces cerevisiae. One of them
      is [SWI+], a prion isoform of the Swi1 protein, which is a component of the
      evolutionarily conserved chromatin remodeling complex SWI/SNF. Earlier, it was
      shown that the prionization of [SWI+] induces a nonsense suppression, which leads
      to weak growth of the [SWI+] strains containing mutant variants of the SUP35 gene
      and the nonsense allele ade1-14UGA on selective medium without adenine. This
      effect occurs because of [SWI+] induction that causes a decrease in the amount of
      the SUP45 mRNA. Strains carrying the SWI1 deletion exhibit significantly higher
      suppression of the ade1-14UGA nonsense mutation than the [SWI+] strains. In the
      present study, we identified genes whose expression is altered in the background
      of the SWI1 deletion using RNA sequencing. We found that the ade1-14UGA
      suppression in the swi1Delta strains is caused by an increase in the expression
      of this mutant allele of the ADE1 gene. At the same time, the SUP45 expression
      level in the swi1Delta strains does not significantly differ from the expression
      level of this gene in the [swi-] strains. Thus, we have shown that the phenotypic
      effects of Swi1 prionization and deletion are mediated by different molecular
      mechanisms. Based on these data, we have concluded that the prionization of
      proteins is not only unequal to their inactivation, but also can lead to the
      acquisition of novel phenotypic effects and functions.

PMID- 29037136
TI  - Effect of Priming of Multipotent Mesenchymal Stromal Cells with Interferon gamma
      on Their Immunomodulating Properties.
AB  - Multipotent mesenchymal stromal cells (MSCs) are widely used for cell therapy, in
      particular for prophylaxis and treatment of graft-versus-host disease. Due to
      their immunomodulatory properties, MSCs affect the composition of lymphocyte
      subpopulations, which depends on the immunological state of the organism and can
      change in different diseases and during treatment. Administration of MSCs is not
      always effective. Treatment of MSCs with different cytokines (in particular IFN
      gamma) leads to enhancement of their immunomodulatory properties. The aim of this
      study was to investigate subpopulational alterations and activation markers in
      lymphocytes (activated and non-activated) after interaction with MSCs and MSCs
      pretreated with IFN-gamma (gammaMSCs) in vitro. Lymphocytes were co-cultured with
      MSCs or gammaMSCs for 4 days. The proportion of CD4+ and CD8+ expressing CD25,
      CD38, CD69, HLA-DR, and PD-1 and distribution of memory and effector subsets were
      measured by flow cytometry after co-cultivation of lymphocytes with MSCs or
      gammaMSCs. The distribution of lymphocyte subpopulations changes during
      culturing. In non-activated lymphocytes cultured without MSCs, decrease in the
      proportion of naive cells and increase in the number of effector cells was
      observed. That could be explained as activation of lymphocytes in the presence of
      serum in culturing medium. Co-culturing of lymphocytes with MSCs and gammaMSCs
      leads to retention of their non-activated state. Activation of lymphocytes with
      phytohemagglutinin increases the number of central memory cells and activates
      marker expression. Interaction with MSCs and gammaMSCs prevents activation of
      lymphocytes and keeps their naive state. Priming with IFN-gamma did not induce
      MSCs inhibitory effect on activation of lymphocytes.

PMID- 29037137
TI  - Heterologous Expression of Chaperones from Hyperthermophilic Archaea Inhibits
      Aminoglycoside-Induced Protein Misfolding in Escherichia coli.
AB  - Aminoglycoside antibiotics affect protein translation fidelity and lead to
      protein aggregation and an increase in intracellular oxidative stress level as
      well. The overexpression of the chaperonin GroEL/GroES system promotes short-term
      tolerance to aminoglycosides in Escherichia coli. Here, we demonstrated that the
      coexpression of prefoldin or Hsp60 originating from the hyperthermophilic
      archaeon Pyrococcus furiosus in E. coli cells can rescue cell growth and inhibit
      protein aggregation induced by streptomycin exposure. The results of our study
      show that hyperthermophilic chaperones endow E. coli with a higher tolerance to
      streptomycin than the GroEL/GroES system, and that they exert better effects on
      the reduction of intracellular protein misfolding, indicating that these
      chaperones have unique features and functions.

PMID- 29037139
TI  - Analysis of Free Amino Acids in Mammalian Brain Extracts.
AB  - An optimized method for analysis of free amino acids using a modified lithium
      citrate buffer system with a Hitachi L-8800 amino acid analyzer is described. It
      demonstrates clear advantages over the sodium-citrate buffer system commonly used
      for the analysis of protein hydrolysates. A sample pretreatment technique for
      amino acid analysis of brain extracts is also discussed. The focus has been
      placed on the possibility of quantitative determination of the reduced form of
      glutathione (GSH) with simultaneous analysis of all other amino acids in brain
      extracts. The method was validated and calibration coefficient (KGSH) was
      determined. Examples of chromatographic separation of free amino acids in
      extracts derived from different parts of the brain are presented.

PMID- 29037138
TI  - N-Acetyl-L-cysteine in the Presence of Cu2+ Induces Oxidative Stress and Death of
      Granule Neurons in Dissociated Cultures of Rat Cerebellum.
AB  - Addition into the culture medium of the antioxidant N-acetylcysteine (NAC, 1 mM)
      in the presence of Cu2+ (0.0005-0.001 mM) induced intensive death of cultured rat
      cerebellar granule neurons, which was significantly decreased by the zinc ion
      chelator TPEN (N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine). However, the
      combined action of NAC and Zn2+ did not induce destruction of the neurons.
      Measurement of the relative intracellular concentration of Zn2+ with the
      fluorescent probe FluoZin-3 AM or of free radical production using a CellROX
      Green showed that incubation of the culture for 4 h with Cu2+ and NAC induced an
      intensive increase in the fluorescence of CellROX Green but not of FluoZin-3.
      Probably, the protective effect of TPEN in this case could be mediated by its
      ability to chelate Cu2+. Incubation of cultures in a balanced salt solution in
      the presence of 0.01 mM Cu2+ caused neuronal death already after 1 h if the NAC
      concentration in the solution was within 0.005-0.05 mM. NAC at higher
      concentrations (0.1-1 mM) together with 0.01 mM Cu2+ did not cause the death of
      neurons. These data imply that the antioxidant NAC can be potentially harmful to
      neurons even in the presence of nanomolar concentrations of variable valence
      metals.

PMID- 29037140
TI  - Blockade of Interleukin 6 by Rat Anti-mouse Interleukin 6 Receptor Antibody
      Promotes Fracture Healing.
AB  - Level of interleukin 6 (IL-6) is associated with fracture healing. This study was
      performed to explore the effect of IL-6 blockade on fracture healing. Clinical
      serum levels of IL-6 and tumor necrosis factor-alpha (TNF-alpha) were evaluated
      by enzyme-linked immunosorbent assay (ELISA). For animal experiments, the IL-6
      levels after fracture and treatment with rat anti-mouse IL-6 receptor antibody
      (MR16-1) were assessed. Then, mice were assigned into four or seven groups:
      control group, fracture group, isotype IgG group, and MR16-1 groups. Serum levels
      of IL-6 and TNF-alpha, relative flexural rigidity, and mRNA levels of osteoblast
      specific genes were respectively assayed by ELISA, three-point bending test, and
      quantitative reverse transcription PCR (qRT-PCR). Serum levels of IL-6 and TNF
      alpha after fracture in humans and mice were increased. The increase in IL-6 and
      TNF-alpha levels in murine serum was attenuated by MR16-1 treatment. The three
      point bending test showed the relative flexural rigidity of the femur was
      decreased after fracture, whereas the decrease was alleviated by MR16-1
      treatment. The qRT-PCR results demonstrated mRNA levels of osteoblast-specific
      genes were upregulated after fracture and then further upregulated by MR16-1
      treatment in a dose-dependent manner. Collectively, the serum level of IL-6 was
      elevated after fracture both in clinical and murine samples. IL-6 blockade by
      MR16-1 promoted fracture healing, which might be associated with changes in
      expression of osteoblast-specific genes.

PMID- 29037141
TI  - Analysis of Four Circulating Complexes of Insulin-Like Growth Factor Binding
      Proteins in Human Blood during Aging.
AB  - The primary role of insulin-like growth factor binding proteins (IGFBPs) is to
      regulate availability of IGFs for interacting with receptors, but IGFBPs perform
      IGF-independent actions as well. The availability and activity of IGFBPs in the
      circulation is influenced primarily by their concentration and structural
      modifications, but possibly also by interaction with major plasma proteins such
      as transferrin, alpha-2-macroglobulin (alpha2M), and fibrinogen. Four types of
      circulating IGFBP complexes were examined in this study by immuno- and ligand
      binding assays in adults of different age. The amounts of IGFBP-3/transferrin and
      IGFBP-1/fibrinogen complexes were similar in middle- and old-aged persons,
      whereas the amounts of IGFBP-1 (or -2)/alpha2M monomer complexes were lower in
      the old-aged group and negatively correlated with total IGFBP-1 (or -2) amounts
      in blood. In contrast to IGFBP-1, IGFBP-2 was present in significantly greater
      quantities in complexes with alpha2M dimer than alpha2M monomer in older
      individuals. IGFBP complexes did not bind 125I-labeled IGF-I in amounts
      detectable by ligand blotting. According to the results of this study, the
      quantities of IGFBP-1 and IGFBP-2, which interact with alpha2M, are age-dependent
      and, in the case of complexes with alpha2M monomer, they are negatively
      correlated with the total circulating levels of these two IGFBPs.

PMID- 29037142
TI  - Enzyme-Substrate Reporters for Evaluation of Substrate Specificity of HIF Prolyl
      Hydroxylase Isoforms.
AB  - An organism naturally responds to hypoxia via stabilization of hypoxia-inducible
      factor (HIF). There are three isoforms of HIFalpha subunits whose stability is
      regulated by three isozymes of HIF prolyl hydroxylase (PHD1-3). Despite intense
      studies on recombinant enzyme isoforms using homogeneous activity assay, there is
      no consensus on the PHD isoform preference for the HIF isoform as a substrate.
      This work provides a new approach to the problem of substrate specificity using
      cell-based reporters expressing the enzyme and luciferase-labeled substrate pair
      encoded in the same expression vector. The cell is used as a microbioreactor for
      running the reaction between the overexpressed enzyme and substrate. Using this
      novel approach, no PHD3 activity toward HIF3 was demonstrated, indirectly
      pointing to the hydroxylation of the second proline in 564PYIP567 (HIF1)
      catalyzed by this isozyme. The use of "paired" enzyme-substrate reporters to
      evaluate the potency of "branched tail" oxyquinoline inhibitors of HIF PHD allows
      higher precision in revealing the optimal structural motif for each enzyme
      isoform.

PMID- 29037143
TI  - Erratum to: "How Fucose of Blood Group Glycotypes Programs Human Gut Microbiota"
      [Biochemistry (Moscow), 82, 973 (2017)].
AB  - This corrects the article DOI: 10.1134/S0006297917090012.

PMID- 29037144
TI  - Trypanosoma cruzi specific mRNA amplification by in vitro transcription improves
      parasite transcriptomics in host-parasite RNA mixtures.
AB  - BACKGROUND: Trypanosomatids are a group of protozoan parasites that includes the
      etiologic agents of important human illnesses as Chagas disease, sleeping
      sickness and leishmaniasis. These parasites have a significant distinction from
      other eukaryotes concerning mRNA structure, since all mature mRNAs have an
      identical species-specific sequence of 39 nucleotides at the 5' extremity, named
      spliced leader (SL). Considering this peculiar aspect of trypanosomatid mRNA, the
      aim of the present work was to develop a Trypanosoma cruzi specific in vitro
      transcription (IVT) linear mRNA amplification method in order to improve parasite
      transcriptomics analyses. METHODS: We designed an oligonucleotide complementary
      to the last 21 bases of T. cruzi SL sequence, bearing an upstream T7 promoter
      (T7SL primer), which was used to direct the synthesis of second-strand cDNA.
      Original mRNA was then amplified by IVT using T7 RNA polymerase. T7SL-amplified
      RNA from two distinct T. cruzi stages (epimastigotes and trypomastigotes) were
      deep sequenced in SOLiD platform. Usual poly(A) + RNA and and T7-oligo(dT)
      amplified RNA (Eberwine method) were also sequenced. RNA-Seq reads were aligned
      to our new and improved T. cruzi Dm28c genome assembly (PacBio technology) and
      resulting transcriptome pattern from these three RNA preparation methods were
      compared, mainly concerning the conservation of mRNA transcritional levels and
      DEGs detection between epimastigotes and trypomastigotes. RESULTS: T7SL IVT
      method detected more potential differentially expressed genes in comparison to
      either poly(A) + RNA or T7dT IVT, and was also able to produce reliable
      quantifications of the parasite transcriptome down to 3 ng of total RNA.
      Furthermore, amplification of parasite mRNA in HeLa/epimastigote RNA mixtures
      showed that T7SL IVT generates transcriptome quantification with similar
      detection of differentially expressed genes when parasite RNA mass was only 0.1%
      of the total mixture (R = 0.78 when compared to poly(A) + RNA). CONCLUSIONS: The
      T7SL IVT amplification method presented here allows the detection of more
      potential parasite differentially expressed genes (in comparison to poly(A) +
      RNA) in host-parasite mixtures or samples with low amount of RNA. This method is
      especially useful for trypanosomatid transcriptomics because it produces less
      bias than PCR-based mRNA amplification. Additionally, by simply changing the
      complementary region of the T7SL primer, the present method can be applied to any
      trypanosomatid species.

PMID- 29037145
TI  - Generalized disequilibrium test for association in qualitative traits
      incorporating imprinting effects based on extended pedigrees.
AB  - BACKGROUND: For dichotomous traits, the generalized disequilibrium test with the
      moment estimate of the variance (GDT-ME) is a powerful family-based association
      method. Genomic imprinting is an important epigenetic phenomenon and currently,
      there has been increasing interest of incorporating imprinting to improve the
      test power of association analysis. However, GDT-ME does not take imprinting
      effects into account, and it has not been investigated whether it can be used for
      association analysis when the effects indeed exist. RESULTS: In this article,
      based on a novel decomposition of the genotype score according to the paternal or
      maternal source of the allele, we propose the generalized disequilibrium test
      with imprinting (GDTI) for complete pedigrees without any missing genotypes.
      Then, we extend GDTI and GDT-ME to accommodate incomplete pedigrees with some
      pedigrees having missing genotypes, by using a Monte Carlo (MC) sampling and
      estimation scheme to infer missing genotypes given available genotypes in each
      pedigree, denoted by MCGDTI and MCGDT-ME, respectively. The proposed GDTI and
      MCGDTI methods evaluate the differences of the paternal as well as maternal
      allele scores for all discordant relative pairs in a pedigree, including beyond
      first-degree relative pairs. Advantages of the proposed GDTI and MCGDTI test
      statistics over existing methods are demonstrated by simulation studies under
      various simulation settings and by application to the rheumatoid arthritis
      dataset. Simulation results show that the proposed tests control the size well
      under the null hypothesis of no association, and outperform the existing methods
      under various imprinting effect models. The existing GDT-ME and the proposed
      MCGDT-ME can be used to test for association even when imprinting effects exist.
      For the application to the rheumatoid arthritis data, compared to the existing
      methods, MCGDTI identifies more loci statistically significantly associated with
      the disease. CONCLUSIONS: Under complete and incomplete imprinting effect models,
      our proposed GDTI and MCGDTI methods, by considering the information on
      imprinting effects and all discordant relative pairs within each pedigree,
      outperform all the existing test statistics and MCGDTI can recapture much of the
      missing information. Therefore, MCGDTI is recommended in practice.

PMID- 29037146
TI  - Comparative genomic analyses highlight the contribution of pseudogenized protein
      coding genes to human lincRNAs.
AB  - BACKGROUND: The regulatory roles of long intergenic noncoding RNAs (lincRNAs) in
      humans have been revealed through the use of advanced sequencing technology.
      Recently, three possible scenarios of lincRNA origins have been proposed: de novo
      origination from intergenic regions, duplication from other long noncoding RNAs,
      and pseudogenization from protein-coding genes. The first two scenarios are
      largely studied and supported, yet few studies focused on the evolution from
      pseudogenized protein-coding sequence to lincRNA. Due to the non-mutually
      exclusive nature of these three scenarios and the need of systematic
      investigation of lincRNA origination, we conducted a comparative genomics study
      to investigate the evolution of human lincRNAs. RESULTS: Combining with syntenic
      analysis and stringent Blastn e-value cutoff, we found that the majority of
      lincRNAs are aligned to intergenic regions of other species. Interestingly, 193
      human lincRNAs could have protein-coding orthologs in at least two of nine
      vertebrates. Transposable elements in these conserved regions in human genome are
      much less than expectation. Moreover, 19% of these lincRNAs have overlaps with or
      are close to pseudogenes in the human genome. CONCLUSIONS: We suggest that a
      notable portion of lincRNAs could be derived from pseudogenized protein-coding
      genes. Furthermore, based on our computational analysis, we hypothesize that a
      subset of these lincRNAs could have potential to regulate their paralogs by
      functioning as competing endogenous RNAs. Our results provide evolutionary
      evidence of the relationship between human lincRNAs and protein-coding genes.

PMID- 29037147
TI  - De novo assembly of genomes from long sequence reads reveals uncharted
      territories of Propionibacterium freudenreichii.
AB  - BACKGROUND: Propionibacterium freudenreichii is an industrially important
      bacterium granted the Generally Recognized as Safe (the GRAS) status, due to its
      long safe use in food bioprocesses. Despite the recognized role in the food
      industry and in the production of vitamin B12, as well as its documented health
      promoting potential, P. freudenreichii remained poorly characterised at the
      genomic level. At present, only three complete genome sequences are available for
      the species. RESULTS: We used the PacBio RS II sequencing platform to generate
      complete genomes of 20 P. freudenreichii strains and compared them in detail.
      Comparative analyses revealed both sequence conservation and genome
      organisational diversity among the strains. Assembly from long reads resulted in
      the discovery of additional circular elements: two putative conjugative plasmids
      and three active, lysogenic bacteriophages. It also permitted characterisation of
      the CRISPR-Cas systems. The use of the PacBio sequencing platform allowed
      identification of DNA modifications, which in turn allowed characterisation of
      the restriction-modification systems together with their recognition motifs. The
      observed genomic differences suggested strain variation in surface piliation and
      specific mucus binding, which were validated by experimental studies. The
      phenotypic characterisation displayed large diversity between the strains in
      ability to utilise a range of carbohydrates, to grow at unfavourable conditions
      and to form a biofilm. CONCLUSION: The complete genome sequencing allowed
      detailed characterisation of the industrially important species, P.
      freudenreichii by facilitating the discovery of previously unknown features. The
      results presented here lay a solid foundation for future genetic and functional
      genomic investigations of this actinobacterial species.

PMID- 29037148
TI  - Effectiveness of a PRECEDE-based education intervention on quality of life in
      elderly patients with chronic heart failure.
AB  - BACKGROUND: One of the most important challenges in public health is to improve
      the quality of life in patients with chronic heart failure (CHF). Depression,
      self-care capacity, and quality of life interact each other in these patients.
      It's difficult to treat with general education programs and conventional therapy.
      PRECEDE model is a comprehensive and exclusive theory-based education programs.
      Its effectiveness for reducing depression and increasing quality of life has been
      demonstrated in patients with coronary artery bypass grafting, type 2 diabetes,
      and the elderly. It has not been used in elderly patients with CHF. Thus, this
      study aims to investigate the effects of this model on self-care behaviors,
      depression, and quality of life in these patients. METHODS: Patients who met the
      inclusion criteria were randomly assigned to the intervention or control group.
      All the patients received conventional medical care. The patients in the
      intervention group also received 9 sessions of education intervention based on
      the PRECEDE model and then followed up for 3 months after the intervention. Data
      were collected before and 3 months after the intervention using 4 questionnaires,
      namely a PRECEDE-based questionnaire to evaluate predisposing, reinforcing, and
      enabling factors; the 9-item European Heart Failure Self-care Behavior Scale
      (EHFScBS-9); the 9-item Personal Health Questionnaire (PHQ-9); and the Minnesota
      Living with Heart Failure Questionnaire (MLHFQ). RESULTS: No significant
      differences were found in the mean scores for the predisposing, enabling, and
      reinforcing factors, and the mean total scores in EHFScBS-9, PHQ-9, and MLHFQ
      before the intervention between the intervention and control groups. After the
      intervention, the scores for the predisposing, reinforcing, and enabling factors
      increased significantly, and the mean total scores in EHFScBS-9, PHQ-9, and MLHFQ
      decreased significantly in the intervention group. In addition, these scores
      significantly differed from those of the control group. Furthermore, the MLHFQ
      score significantly correlated with the EHFScBS-9 and PHQ-9 scores. CONCLUSION:
      This study demonstrates a trend that PRECEDE model of health education promotion
      is effective in relieving depression symptoms, enhancing self-monitoring, and
      improving the quality of life of elderly patients with CHF. TRIAL REGISTRATION:
      Trial registration number: ChiCTR-IOR-17012779 ; Trial registry: Chinese Clinical
      Trial Registry; Date registered: 22 Sep 2017; Retrospectively registered.

PMID- 29037149
TI  - chngpt: threshold regression model estimation and inference.
AB  - BACKGROUND: Threshold regression models are a diverse set of non-regular
      regression models that all depend on change points or thresholds. They provide a
      simple but elegant and interpretable way to model certain kinds of nonlinear
      relationships between the outcome and a predictor. RESULTS: The R package chngpt
      provides both estimation and hypothesis testing functionalities for four common
      variants of threshold regression models. All allow for adjustment of additional
      covariates not subjected to thresholding. We demonstrate the consistency of the
      estimating procedures and the type 1 error rates of the testing procedures by
      Monte Carlo studies, and illustrate their practical uses using an example from
      the study of immune response biomarkers in the context of Mother-To-Child
      Transmission of HIV-1 viruses. CONCLUSION: chngpt makes several unique
      contributions to the software for threshold regression models and will make these
      models more accessible to practitioners interested in modeling threshold effects.

PMID- 29037150
TI  - Genome-wide trait-trait dynamics correlation study dissects the gene regulation
      pattern in maize kernels.
AB  - BACKGROUND: Dissecting the genetic basis and regulatory mechanisms for the
      biosynthesis and accumulation of nutrients in maize could lead to the improved
      nutritional quality of this crop. Gene expression is regulated at the genomic,
      transcriptional, and post-transcriptional levels, all of which can produce
      diversity among traits. However, the expression of most genes connected with a
      particular trait usually does not have a direct association with the variation of
      that trait. In addition, expression profiles of genes involved in a single
      pathway may vary as the intrinsic cellular state changes. To work around these
      issues, we utilized a statistical method, liquid association (LA) to investigate
      the complex pattern of gene regulation in maize kernels. RESULTS: We applied LA
      to the expression profiles of 28,769 genes to dissect dynamic trait-trait
      correlation patterns in maize kernels. Among the 1000 LA pairs (LAPs) with the
      largest LA scores, 686 LAPs were identified conditional correlation. We also
      identified 830 and 215 LA-scouting leaders based on the positive and negative LA
      scores, which were significantly enriched for some biological processes and
      molecular functions. Our analysis of the dynamic co-expression patterns in the
      carotene biosynthetic pathway clearly indicated the important role of lcyE,
      CYP97A, ZEP1, and VDE in this pathway, which may change the direction of carotene
      biosynthesis by controlling the influx and efflux of the substrate. The dynamic
      trait-trait correlation patterns between gene expression and oil concentration in
      the fatty acid metabolic pathway and its complex regulatory network were also
      assessed. 23 of 26 oil-associated genes were correlated with oil concentration
      conditioning on 580 LA-scoutinggenes, and 5% of these LA-scouting genes were
      annotated as enzymes in the oil metabolic pathway. CONCLUSIONS: By focusing on
      the carotenoid and oil biosynthetic pathways in maize, we showed that a genome
      wide LA analysis provides a novel and effective way to detect transcriptional
      regulatory relationships. This method will help us understand the biological role
      of maize kernel genes and will benefit maize breeding programs.

PMID- 29037151
TI  - Lipidomics analysis unravels the effect of nitrogen fertilization on lipid
      metabolism in tea plant (Camellia sinensis L.).
AB  - BACKGROUND: Nitrogen (N) plays an important role in the formation of tea quality
      related compounds, like amino acids and flavor/aroma origin compounds. Lipids,
      which have been reported to be affected by N deficiency, are precursors to the
      generation of flavor/aroma origin compounds in tea plant. However, there is no
      literature about the lipid profiles of tea plant affected by N fertilization.
      Hence, we hypothesize that the biosynthesis of flavor-related compounds in tea
      was affected by N through its regulation of lipid metabolism. RESULTS: In this
      study, mature leaves and new shoots of tea plant grown under three N levels at
      the rates of 0, 285 and 474 kg/ha were applied for ultra-performance liquid
      chromatography-mass spectrometry (UPLC/MS) based lipidomic analysis. Totally, 178
      lipid species were identified. The results showed that the composition of lipid
      compounds in mature leaves and new shoots varied dramatically, which was also
      affected by N levels. The higher content of the storage lipid TAG and higher
      carbon (C)/N ratio in mature leaves than that of new shoots in tea plants grown
      under low N level (0 kg/ha) suggested that tea plants could remobilize the C
      stored in TAG to maintain their C/N balance and help to improve the quality of
      tea. N fertilization resulted in a higher content of the compounds 36:6 MGDG and
      36:6 DGDG. Since these compounds contain linolenic acid (18:3), a precursor to
      the formation of aroma origin compounds, we suggested their increase could
      contribute to the quality of tea. CONCLUSIONS: Taken together, the present work
      indicated that appropriate application of N fertilizer could balance the lipid
      metabolism and the formation of flavor/aroma origin compounds, which help to
      improve the quality of tea. Moreover, excess N fertilization might deteriorate
      the aroma quality of made tea due to increases of precursors leading to grassy
      odor.

PMID- 29037152
TI  - Low plasma tryptophan is associated with olfactory function in healthy elderly
      community dwellers in Japan.
AB  - BACKGROUND: Decreased circulating tryptophan (Trp) levels are frequently observed
      in elderly patients with neurodegenerative disease including Alzheimer's disease.
      Trp may serve as a potential biomarker for monitoring disease risk in elderly
      people. We aimed to investigate the association between low plasma Trp levels and
      olfactory function, which is known to predict age-related diseases including
      dementia in elderly people. METHODS: A total of 144 healthy elderly Japanese
      community (>= 65 years old) dwellers from the Health, Aging and Nutritional
      Improvement study (HANI study) were the subjects of our analysis. Low Trp levels
      were classified using the lower limit values of the reference interval according
      to a previous report. Olfactory function was assessed using a card-type test
      called Open Essence, which includes 12 odour items that are familiar to Japanese
      people. The elderly subjects with low circulating Trp levels were compared to a
      control group with normal plasma Trp levels. RESULTS: We conducted the analyses
      using 144 people aged 65 years or older (mean age 73.7 +/- 5.5 years; 36.1% men).
      The subjects showed normal serum albumin levels (4.4 +/- 0.2 g/dL) and no daily
      living disabilities. Low plasma Trp levels (low Trp group) were found in 11.1% of
      the study population. The low Trp group showed a significantly lower correct
      answer rate for the items india ink, perfume, curry and sweaty smelling socks
      than control group (P < 0.05). There was also a significant association between
      low Trp levels and low olfactory ability, after adjusting for age and sex.
      CONCLUSIONS: Lower plasma Trp levels were associated with a decrease in olfactory
      function in functionally competent older individuals. Because olfactory
      dysfunction predicts age-related diseases, low plasma Trp levels may represent a
      clinical sign of disease risk in elderly people.

PMID- 29037154
TI  - An inappropriate pacing threshold increase after repeated electrical storm in a
      patient with implantable cardioverter defibrillator.
AB  - BACKGROUND: Implantable cardioverter defibrillators (ICD) are capable of
      effectively terminating malignant ventricular arrhythmia and are the most
      effective way to prevent sudden cardiac death. However, some evidences
      demonstrated that both anti-tachycardia pacing (ATP) and ICD shock can also bring
      adverse prognosis. CASE PRESENTATION: A 66-year-old Han Chinese man with prior
      ICD implantation was admitted to our hospital because of frequent ICD shocks.
      Although intravenous amiodarone and esmolol succinate were administered daily,
      the patient suffered 155 episodes of VT/VF during 8 weeks after implantation.
      After repeated discharge of the device, the pacing threshold of the patient
      increased gradually. Considering the inappropriate increase of the pacing
      threshold, we decided to reposition the right ventricular (RV) lead with good
      sensing and threshold parameters confirmed. Subsequent 22 months interrogation
      follow-up revealed a stable lead position and electrical specifications.
      Furthermore, antiarrhythmic drugs were maximally increased, while ATP burst was
      remarkably decreased and the inappropriate ICD shock never occurred until now.
      CONCLUSION: An inappropriate pacing threshold was increased secondary to repeated
      ICD electrical storm. A timely active lead position adjustment reduced the pacing
      threshold and eliminated the risk of premature battery depletion.

PMID- 29037153
TI  - Wound healing, calcium signaling, and other novel pathways are associated with
      the formation of butterfly eyespots.
AB  - BACKGROUND: One hypothesis surrounding the origin of novel traits is that they
      originate from the co-option of pre-existing genes or larger gene regulatory
      networks into novel developmental contexts. Insights into a trait's evolutionary
      origins can, thus, be gained via identification of the genes underlying trait
      development, and exploring whether those genes also function in other
      developmental contexts. Here we investigate the set of genes associated with the
      development of eyespot color patterns, a trait that originated once within the
      Nymphalid family of butterflies. Although several genes associated with eyespot
      development have been identified, the eyespot gene regulatory network remains
      largely unknown. RESULTS: In this study, next-generation sequencing and
      transcriptome analyses were used to identify a large set of genes associated with
      eyespot development of Bicyclus anynana butterflies, at 3-6 h after pupation,
      prior to the differentiation of the color rings. Eyespot-associated genes were
      identified by comparing the transcriptomes of homologous micro-dissected wing
      tissues that either develop or do not develop eyespots in wild-type and a mutant
      line of butterflies, Spotty, with extra eyespots. Overall, 186 genes were
      significantly up and down-regulated in wing tissues that develop eyespots
      compared to wing tissues that do not. Many of the differentially expressed genes
      have yet to be annotated. New signaling pathways, including the Toll, Fibroblast
      Growth Factor (FGF), extracellular signal-regulated kinase (ERK) and/or Jun N
      terminal kinase (JNK) signaling pathways are associated for the first time with
      eyespot development. In addition, several genes involved in wound healing and
      calcium signaling were also found to be associated with eyespots. CONCLUSIONS:
      Overall, this study provides the identity of many new genes and signaling
      pathways associated with eyespots, and suggests that the ancient wound healing
      gene regulatory network may have been co-opted to cells at the center of the
      pattern to aid in eyespot origins. New transcription factors that may be
      providing different identities to distinct wing sectors, and genes with sexually
      dimorphic expression in the eyespots were also identified.

PMID- 29037156
TI  - The association of obstructive sleep apnea and renal outcomes-a systematic review
      and meta-analysis.
AB  - BACKGROUND: The aim of this systematic review and meta-analysis was to summarize
      the association of obstructivesleep apnea (OSA) with renal outcome. METHODS: Our
      study followed the PRISMA guidelines. Two independent reviewers searched for
      relevant articles inthe databases of Pubmed, the Web of Science and CENTRAL, and
      conducted study selection and quality assessment. A random-effect model was used
      to estimate the effects. RESULTS: total of 1240 articles were initially
      identified (Pubmed = 568, Web of Science = 640, CENTRAL = 32). Afterremoval of
      duplicate articles (n = 415) and irrelevant articles (n = 788), 37 were selected
      for full-text review, and 18were finally included in the analysis. Overall,
      patients diagnosed with OSA were found to have a higher odds ratio (OR) of a
      poorer renal outcome, with a pooled OR of 1.77 (95% C.I.: 1.37-2.29). The
      significant association between OSA and a poorer renal outcome was not affected
      by the medical condition of diabetes mellitus (DM). In addition, we found that
      OSA was consistently associated with higher albuminuria/proteinuria and a lower
      estimated glomerular filtration rate (eGFR), with a pooled OR of 1.84 (95% C.I.:
      1.24-2.73) and 1.60 (95% C.I.: 1.19-2.16), respectively. A greater OSA severity
      was also found to be related to a higher OR, with a mild group OR of 1.45 (95%
      C.I.: 1.19-1.77) and a moderate and severe group OR of 2.39 (95% C.I.: 1.96
      2.90). CONCLUSIONS: Our study demonstrated that OSA is significantly associated
      with poorer renal function.

PMID- 29037155
TI  - Differences in handgrip strength protocols to identify sarcopenia and frailty - a
      systematic review.
AB  - BACKGROUND: Hand grip strength (HGS) is used for the diagnosis of sarcopenia and
      frailty. Several factors have been shown to influence HGS values during
      measurement. Therefore, variations in the protocols used to assess HGS, as part
      of the diagnosis of sarcopenia and frailty, may lead to the identification of
      different individuals with low HGS, introducing bias. The aim of this systematic
      review is to gather all the relevant studies that measured HGS to diagnose
      sarcopenia and frailty and to identify the differences between the protocols
      used. METHODS: A systematic review was carried out following the recommendations
      of The Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA) Statement. PubMed and Web of Science were systematically searched, until
      August 16, 2016. The evidence regarding HGS measurement protocols used to
      diagnose sarcopenia and frailty was summarised and the most recent protocols
      regarding the procedure were compared. RESULTS: From the described search 4393
      articles were identified. Seventy-two studies were included in this systematic
      review, in which 37 referred to sarcopenia articles, 33 to frailty and two
      evaluated both conditions. Most studies presented limited information regarding
      the protocols used. CONCLUSIONS: The majority of the studies included did not
      describe a complete procedure of HGS measurement. The high heterogeneity between
      the protocols used, in sarcopenia and frailty studies, create an enormous
      difficulty in drawing comparative conclusions among them.

PMID- 29037157
TI  - Gastrointestinal motility following thoracic surgery: the effect of thoracic
      epidural analgesia. A randomised controlled trial.
AB  - BACKGROUNDS: Impairment of gastrointestinal (GI) motility is an undesirable but
      inevitable consequence of surgery. This prospective randomised controlled study
      tested the hypothesis that postoperative thoracic epidural analgesia (TEA) with
      ropivacaine or a combination of ropivacaine and morphine accelerates
      postoperative GI function and shortens the duration of postoperative ileus
      following major thoracic surgery compared to intravenous (IV) morphine. METHODS:
      Thirty patients scheduled for major thoracic surgery were randomised to three
      groups. All patients had bowel motility assessments 1 week preoperatively. All
      patients received general anaesthesia. Group Ep-R received TEA with ropivacaine;
      group Ep-RM received TEA with ropivacaine and morphine and group IV-M received IV
      morphine via patient controlled analgesia pump (PCA). Bowel motility was assessed
      by clinical examination in addition to oro-ceacal transit time (OCTT) on the
      first and third postoperative days and colonic transit time (CTT). RESULTS:
      Overall the OCTT demonstrated a 2.5-fold decrease in bowel motility on the first
      postoperative day. The OCTT test revealed statistically significant differences
      between all groups (Ep-R vs Ep-RM, p = 0.43/Ep-R vs IV-M, p = 0.039 / Ep-RM vs IV
      M, p < 0.001). Also, very significant differences were found in the OCCT test
      between days (Ep-R vs Ep-RM, p < 0.001/Ep-R vs IV-M, p < 0.001 / Ep-RM vs IV-M, p
      = 0.014). There were no significant differences in the CTT test or the clinical
      signs between groups. However, 70% of the patients in the Ep-R group and 80% in
      the Ep-RM group defecated by the third day compared to only 10% in the IV-M
      group, (p = 0.004). CONCLUSIONS: Objective tests demonstrated the delayed
      motility of the whole GI system postoperatively following thoracic surgery. They
      also demonstrated that continuous epidural analgesia with or without morphine
      improved GI motility in comparison to intravenous morphine. These differences
      were more pronounced on the third postoperative day. TRIAL REGISTRATION: ISRCTN
      number: 11953159 , retrospectively registered on 20/03/2017.

PMID- 29037159
TI  - Bowel perforation by a peritoneal dialysis catheter: report of two cases.
AB  - BACKGROUND: Complications of peritoneal dialysis (PD) such as pain and catheter
      leakage are frequently reported. Delayed bowel perforation of a PD catheter is a
      rare adverse event but a serious complication associated with significant
      mortality. Bowel perforation of a PD catheter is difficult to differentiate from
      PD-related peritonitis and likely to result in a delay in diagnosis. Here, we
      report two cases of bowel perforation after PD catheter insertion by the stepwise
      initiation of PD using the Moncrief and Popovich technique (SMAP) and peritoneal
      wall anchor technique (PWAT). CASE PRESENTATION: The first case was a 53-year-old
      woman with end-stage renal disease (ESRD) due to diabetic nephropathy and a
      history of entero-adhesiolysis. She underwent PD catheter insertion by the SMAP
      with PWAT. Four months after PD catheter insertion, the catheter was found to
      perforate sigmoid colon. The second case was a 57-year-old woman with ESRD due to
      large polycystic kidney disease. She underwent the same procedure. After
      exteriorization of the catheter, she developed peritonitis due to perforation of
      the catheter tip into the bowel. Both patients were safely removed the catheter
      with uneventful recovery. CONCLUSION: We reported two cases of a rare
      complication of PD catheter. The SMAP method, PWAT, enlarged kidneys and
      migration of the lower cuff may be risk factors of bowel perforation of a PD
      catheter.

PMID- 29037158
TI  - Genomic divergence and cohesion in a species of pelagic freshwater bacteria.
AB  - BACKGROUND: In many prokaryotic genera a clustered phylogeny is observed, akin to
      the occurrence of species in sexually reproducing organisms. For some taxa,
      homologous recombination has been invoked as the underlying mechanism providing
      genomic cohesion among conspecific individuals. Whether this mechanism is
      applicable to prokaryotes in freshwaters with low habitat connectivity - i.e.
      elevated geographic barriers to gene flow - is unclear. To investigate further we
      studied genomic trends within the globally abundant PnecC cluster (genus
      Polynucleobacter, Betaproteobacteria) and analyzed homologous recombination
      within the affiliated species P. asymbioticus. RESULTS: Comparisons among 20
      PnecC genomes revealed a clearly discontinuous distribution of nucleotide
      sequence similarities. Among the nine conspecific individuals (P. asymbioticus)
      all average nucleotide identity (ANI) values were greater than 97%, whereas all
      other comparisons exhibited ANI values lower than 85%. The reconstruction of
      recombination and mutation events for the P. asymbioticus core genomes yielded an
      r/m ratio of 7.4, which is clearly above estimated thresholds for recombination
      to act as a cohesive force. Hotspots of recombination were found to be located in
      the flanking regions of genomic islands. Even between geographically separated
      habitats a high flux of recombination was evident. While a biogeographic
      population structure was suggested from MLST data targeting rather conserved
      loci, such a structure was barely visible when whole genome data was considered.
      However, both MLST and whole genome data showed evidence of differentiation
      between two lineages of P. asymbioticus. The ratios of non-synonymous to
      synonymous substitution rates as well as growth rates in transplantation
      experiments suggested that this divergence was not selectively neutral.
      CONCLUSIONS: The high extent of homologous recombination among P. asymbioticus
      bacteria can act as a cohesive force that effectively counteracts genetic
      divergence. At least on a regional scale, homologous recombination can act across
      geographically separated ecosystems and therefore plays an important role in the
      evolution and consistency of bacterial freshwater species. A species model akin
      to the biological species concept may be applicable for P. asymbioticus.
      Nonetheless, two genetically distinct lineages have emerged and further research
      may clarify if their divergence has been initiated by reinforced geographical
      barriers or has been evolving in sympatry.

PMID- 29037160
TI  - "Homozygous, and compound heterozygous mutation in 3 Turkish family with Jervell
      and Lange-Nielsen syndrome: case reports".
AB  - BACKGROUND: Jervell and Lange-Nielsen syndrome (JLNS) isa recessive model of long
      QT syndrome which might also be related to possible hearing loss. Although the
      syndrome has been demonstrated to be originated from homozygous or compound
      heterozygous mutations in either the KCNQ1 or KCNE1 genes, additional mutations
      in other genetic loci should be considered, particularly in malignant course
      patients. CASE PRESENTATIONS: Three patients were admitted into hospital due to
      recurrent seizures/syncope, intrauterine and postnatal bradycardia respectively;
      moreover all three patients had congenital sensorineural hearing-loss. Their
      electrocardiograms showed markedly prolonged QT interval. Implantable
      defibrillator was implanted and left cardiac sympathetic denervation was
      performed due to the progressive disease in case 1. She had countless ventricular
      fibrillation and appropriate shock while using an implantable defibrillator. The
      DNA sequencing analysis of the KCNQ1 gene disclosed a homozygous c.728G > A
      (p.Arg243His) missense mutation in case1. Further targeted next generation
      sequencing of cardiac panel comprising 68 gene revealed a heterozygous c.1346 T >
      G (p.Ile449Arg) variant in RYR2 gene and a heterozygous c.809G > A (p.Cys270Tyr)
      variant in NKX2-5 gene in the same patient. Additional gene alterations in RYR2
      and NKX2-5 genes were thought to be responsible for progressive and malignant
      course of the disease. As a result of DNA sequencing analysis of KCNQ1 and KCNE1
      genes, a compound heterozygosity for two mutations had been detected in KCNQ1
      gene in case 2: a maternally derived c.477 + 1G > A splice site mutation and a
      paternally derived c.520C > T (p.Arg174Cys) missense mutation. Sanger sequencing
      of KCNQ1 and KCNE1 genes displayed a homozygous c.1097G > A (p.Arg366Gln)
      mutation in KCNQ1 gene in case 3. beta-blocker therapy was initiated to all the
      index subjects. CONCLUSIONS: Three families of JLNS who presented with long QT
      and deafness and who carry homozygous, or compound heterozygous mutation in KCNQ1
      gene were presented in this report. It was emphasized that broad targeted cardiac
      panels may be useful to predict the outcome especially in patients with
      unexplained phenotype-genotype correlation. Clinical presentations and molecular
      findings will be discussed further to clarify the phenotype genotype
      associations.

PMID- 29037161
TI  - Transcript expression plasticity as a response to alternative larval host plants
      in the speciation process of corn and rice strains of Spodoptera frugiperda.
AB  - BACKGROUND: Our main purpose was to evaluate the expression of plastic and
      evolved genes involved in ecological speciation in the noctuid moth Spodoptera
      frugiperda, the fall armyworm (FAW); and to demonstrate how host plants might
      influence lineage differentiation in this polyphagous insect. FAW is an important
      pest of several crops worldwide, and it is differentiated into host plant-related
      strains, corn (CS) and rice strains (RS). RNA-Seq and transcriptome
      characterization were applied to evaluate unbiased genetic expression differences
      in larvae from the two strains, fed on primary (corn) and alternative (rice) host
      plants. We consider that genes that are differently regulated by the same FAW
      strain, as a response to different hosts, are "plastic". Otherwise, differences
      in gene expression between the two strains fed on the same host are considered
      constitutive differences. RESULTS: Individual performance parameters (larval and
      pupal weight) varied among conditions (strains vs. hosts). A total of 3657
      contigs was related to plastic response, and 2395 contigs were differentially
      regulated in the two strains feeding on preferential and alternative hosts
      (constitutive contigs). Three molecular functions were present in all
      comparisons, both down- and up-regulated: oxidoreductase activity, metal-ion
      binding, and hydrolase activity. CONCLUSIONS: Metabolization of foreign chemicals
      is among the key functions involved in the phenotypic variation of FAW strains.
      From an agricultural perspective, high plasticity in families of detoxifying
      genes indicates the capacity for a rapid response to control compounds such as
      insecticides.

PMID- 29037162
TI  - Feasibility of a multi-modal exercise program on cognition in older adults with
      Type 2 diabetes - a pilot randomised controlled trial.
AB  - BACKGROUND: Type 2 Diabetes (T2D) is associated with increased risk of dementia.
      We aimed to determine the feasibility of a randomised controlled trial (RCT)
      examining the efficacy of exercise on cognition and brain structure in people
      with T2D. METHODS: A 6-month pilot parallel RCT of a progressive aerobic- and
      resistance-training program versus a gentle movement control group in people with
      T2D aged 50-75 years (n = 50) at the University of Tasmania, Australia. Assessors
      were blinded to group allocation. Brain volume (total, white matter,
      hippocampus), cortical thickness and white matter microstructure (fractional
      anisotrophy and mean diffusivity) were measured using magnetic resonance imaging,
      and cognition using a battery of neuropsychological tests. Study design was
      assessed by any changes (during the pilot or recommended) to the protocol,
      recruitment by numbers screened and time to enrol 50 participants; randomisation
      by similarity of characteristics in groups at baseline, adherence by exercise
      class attendance; safety by number and description of adverse events and
      retention by numbers withdrawn. RESULTS: The mean age of participants was 66.2
      (SD 4.9) years and 48% were women. There were no changes to the design during the
      study. A total of 114 people were screened for eligibility, with 50 participants
      with T2D enrolled over 8 months. Forty-seven participants (94%) completed the
      study (23 of 24 controls; 24 of 26 in the intervention group). Baseline
      characteristics were reasonably balanced between groups. Exercise class
      attendance was 79% for the intervention and 75% for the control group. There were
      6 serious adverse events assessed as not or unlikely to be due to the
      intervention. Effect sizes for each outcome variable are provided. CONCLUSION:
      This study supports the feasibility of a large scale RCT to test the benefits of
      multi-modal exercise to prevent cognitive decline in people with T2D. Design
      changes to the future trial are provided. TRIAL REGISTRATION: ANZCTR
      12614000222640 ; Registered 3/3/2014; First participant enrolled 26/6/2014, study
      screening commenced 1/9/2014; Australian and New Zealand Clinical Trial Registry.

PMID- 29037163
TI  - Diagnostic performance of various familial hypercholesterolaemia diagnostic
      criteria compared to Dutch lipid clinic criteria in an Asian population.
AB  - BACKGROUND: Familial hypercholesterolaemia (FH) is a genetic disorder with a high
      risk of developing premature coronary artery disease that should be diagnosed as
      early as possible. Several clinical diagnostic criteria for FH are available,
      with the Dutch Lipid Clinic Criteria (DLCC) being widely used. Information
      regarding diagnostic performances of the other criteria against the DLCC is
      scarce. We aimed to examine the diagnostic performance of the Simon-Broom (SB)
      Register criteria, the US Make Early Diagnosis to Prevent Early Deaths (US
      MEDPED) and the Japanese FH Management Criteria (JFHMC) compared to the DLCC.
      METHODS: Seven hundered fifty five individuals from specialist clinics and
      community health screenings with LDL-c level >= 4.0 mmol/L were selected and
      diagnosed as FH using the DLCC, the SB Register criteria, the US MEDPED and the
      JFHMC. The sensitivity, specificity, efficiency, positive and negative predictive
      values of individuals screened with the SB register criteria, US MEDPED and JFHMC
      were assessed against the DLCC. RESULTS: We found the SB register criteria
      identified more individuals with FH compared to the US MEDPED and the JFHMC (212
      vs. 105 vs. 195; p < 0.001) when assessed against the DLCC. The SB Register
      criteria, the US MEDPED and the JFHMC had low sensitivity (51.1% vs. 25.3% vs.
      47.0% respectively). The SB Register criteria showed better diagnostic
      performance than the other criteria with 98.8% specificity, 28.6% efficiency
      value, 98.1% and 62.3% for positive and negative predictive values respectively.
      CONCLUSION: The SB Register criteria appears to be more useful in identifying
      positive cases leading to genetic testing compared to the JFHMC and US MEDPED in
      this Asian population. However, further research looking into a suitable
      diagnosis criterion with high likelihood of positive genetic findings is required
      in the Asian population including in Malaysia.

PMID- 29037164
TI  - Local epidemiology and resistance profiles in acute uncomplicated cystitis (AUC)
      in women: a prospective cohort study in an urban urological ambulatory setting.
AB  - BACKGROUND: Acute uncomplicated cystitis (AUC) is a common ailment in the
      urological setting. Guidelines for urinary tract infections are based on large
      scale multi-centre, epidemiological and international studies. The objective of
      this observational study was to establish whether the results of a multi-centre
      study on the resistance profile of Escherichia coli (E. coli) in patients with
      AUC could be directly applied to an urological practice in a major European city
      or whether there are divergences in the resistance profile. METHODS: An
      observational study was applied prospectively to 502 patients with AUC between
      January 2015 and January 2017). Personal data were anonymised. Exclusion criteria
      were the patient's age (<18) and treatment with an antibiotic in the week
      preceding examination. RESULTS: The average age was 32 (range 18-56). The most
      commonly detected bacteria was E. coli with 86%, followed by Enterococcus
      faecalis with 10% and Klebsiella pneumoniae with 4%. Resistance tests showed E.
      coli to be highly sensitive to fosfomycin (99.2%), nitrofurantoin (98.1%) and
      cefpodoxime (92.9%). E. coli exhibited resistance to ciprofloxacin (CIP) in
      15.1%, to trimethoprim/sulfamethoxazole (TRS) in 25.2% and to
      amoxicillin/clavulanic acid (AMC) in 34% of cases. CONCLUSION: The comparison
      between data from this study and data from a multi-centre European (ECO-SENSI,
      ECO-SENSII and the 2014 update) showed relatively good sensitivity rates for
      fosfomycin and nitrofurantoin but significant differences in respect of
      resistance levels to TRS, CIP and AMC. AUC should therefore only be treated with
      TRS, CIP and AMC after a susceptibility test has been carried out.

PMID- 29037166
TI  - TaFlo2-A1, an ortholog of rice Flo2, is associated with thousand grain weight in
      bread wheat (Triticum aestivum L.).
AB  - BACKGROUND: The Flo2 gene is a member of a conserved gene family in plants. This
      gene has been found to be related to thousand grain weight (TGW) in rice. Its
      orthologs in hexaploid wheat were cloned, and the haplotype variation in TaFlo2
      A1 was tested for association with TGW. RESULTS: The cloned sequences of TaFlo2
      A1, TaFlo2-B1 and TaFlo2-D1 contained 23, 23 and 24 exons, respectively. The
      deduced proteins of TaFlo2-A1 (1734 aa), TaFlo2-B1 (1698 aa) and TaFlo2-D1 (1682
      aa) were highly similar (>94%) and exhibited >77% similarity with the rice FLO2
      protein. Like the rice FLO2 protein, four tetratricopeptide repeat (TPR) motifs
      were observed in the deduced TaFLO2 protein. An 8-bp InDel (-10 to -17 bp) in the
      promoter region and five SNPs in first intron of TaFlo2-A1 together formed two
      haplotypes, TaFlo2-A1a and TaFlo2-A1b, in bread wheat. TaFlo2 was located on
      homeologous group 2 chromosomes. TaFlo2-A1 was inferred to be located on deletion
      bin '2AL1-0.85-1.00'. The TaFlo2-A1 haplotypes were characterized in the Chinese
      Micro Core Collection (MCC) and Pakistani wheat collection using the molecular
      marker TaFlo2-Indel8. TaFlo2-A1 was found to be associated with TGW but not with
      grain number per spike (GpS) in both the MCC and Pakistani wheat collections. The
      frequency of TaFlo2-A1b (positive haplotype) was low in commercial wheat
      cultivars; thus this haplotype can be selected to improve grain weight without
      negatively affecting GpS. The expression level of TaFlo2-A1 in developing grains
      at 5 DAF (days after flowering) was positively correlated with TGW in cultivars
      carrying the positive haplotype. CONCLUSION: This study will likely lead to
      additional investigations to understand the regulatory mechanism of the Flo2 gene
      in hexaploid wheat. Furthermore, the newly developed molecular marker 'TaFlo2
      InDel8' could be incorporated into the kit of wheat breeders for use in marker
      assisted selection.

PMID- 29037165
TI  - Sequencing flow-sorted short arm of Haynaldia villosa chromosome 4V provides
      insights into its molecular structure and virtual gene order.
AB  - BACKGROUND: Haynaldia villosa (H. villosa) has been recognized as a species
      potentially useful for wheat improvement. The availability of its genomic
      sequences will boost its research and application. RESULTS: In this work, the
      short arm of H. villosa chromosome 4V (4VS) was sorted by flow cytometry and
      sequenced using Illumina platform. About 170.6 Mb assembled sequences were
      obtained. Further analysis showed that repetitive elements accounted for about
      64.6% of 4VS, while the coding fraction, which is corresponding to 1977 annotated
      genes, represented 1.5% of the arm. The syntenic regions of the 4VS were searched
      and identified on wheat group 4 chromosomes 4AL, 4BS, 4DS, Brachypodium
      chromosomes 1 and 4, rice chromosomes 3 and 11, and sorghum chromosomes 1, 5 and
      8. Based on genome-zipper analysis, a virtual gene order comprising 735 gene loci
      on 4VS genome was built by referring to the Brachypodium genome, which was
      relatively consistent with the scaffold order determined for Ae. tauschii
      chromosome 4D. The homologous alleles of several cloned genes on wheat group 4
      chromosomes including Rht-1 gene were identified. CONCLUSIONS: The sequences
      provided valuable information for mapping and positional-cloning genes located on
      4VS, such as the wheat yellow mosaic virus resistance gene Wss1. The work on 4VS
      provided detailed insights into the genome of H. villosa, and may also serve as a
      model for sequencing the remaining parts of H. villosa genome.

PMID- 29037167
TI  - Ancestry inference using principal component analysis and spatial analysis: a
      distance-based analysis to account for population substructure.
AB  - BACKGROUND: Accurate inference of genetic ancestry is of fundamental interest to
      many biomedical, forensic, and anthropological research areas. Genetic ancestry
      memberships may relate to genetic disease risks. In a genome association study,
      failing to account for differences in genetic ancestry between cases and controls
      may also lead to false-positive results. Although a number of strategies for
      inferring and taking into account the confounding effects of genetic ancestry are
      available, applying them to large studies (tens thousands samples) is
      challenging. The goal of this study is to develop an approach for inferring
      genetic ancestry of samples with unknown ancestry among closely related
      populations and to provide accurate estimates of ancestry for application to
      large-scale studies. METHODS: In this study we developed a novel distance-based
      approach, Ancestry Inference using Principal component analysis and Spatial
      analysis (AIPS) that incorporates an Inverse Distance Weighted (IDW)
      interpolation method from spatial analysis to assign individuals to population
      memberships. RESULTS: We demonstrate the benefits of AIPS in analyzing population
      substructure, specifically related to the four most commonly used tools
      EIGENSTRAT, STRUCTURE, fastSTRUCTURE, and ADMIXTURE using genotype data from
      various intra-European panels and European-Americans. While the aforementioned
      commonly used tools performed poorly in inferring ancestry from a large number of
      subpopulations, AIPS accurately distinguished variations between and within
      subpopulations. CONCLUSIONS: Our results show that AIPS can be applied to large
      scale data sets to discriminate the modest variability among intra-continental
      populations as well as for characterizing inter-continental variation. The method
      we developed will protect against spurious associations when mapping the genetic
      basis of a disease. Our approach is more accurate and computationally efficient
      method for inferring genetic ancestry in the large-scale genetic studies.

PMID- 29037168
TI  - Locating helicopter emergency medical service bases to optimise population
      coverage versus average response time.
AB  - BACKGROUND: New South Wales (NSW), Australia has a network of multirole retrieval
      physician staffed helicopter emergency medical services (HEMS) with seven bases
      servicing a jurisdiction with population concentrated along the eastern seaboard.
      The aim of this study was to estimate optimal HEMS base locations within NSW
      using advanced mathematical modelling techniques. METHODS: We used high
      resolution census population data for NSW from 2011 which divides the state into
      areas containing 200-800 people. Optimal HEMS base locations were estimated using
      the maximal covering location problem facility location optimization model and
      the average response time model, exploring the number of bases needed to cover
      various fractions of the population for a 45 min response time threshold or
      minimizing the overall average response time to all persons, both in green field
      scenarios and conditioning on the current base structure. We also developed a
      hybrid mathematical model where average response time was optimised based on
      minimum population coverage thresholds. RESULTS: Seven bases could cover 98% of
      the population within 45mins when optimised for coverage or reach the entire
      population of the state within an average of 21mins if optimised for response
      time. Given the existing bases, adding two bases could either increase the 45 min
      coverage from 91% to 97% or decrease the average response time from 21mins to
      19mins. Adding a single specialist prehospital rapid response HEMS to the area of
      greatest population concentration decreased the average state wide response time
      by 4mins. The optimum seven base hybrid model that was able to cover 97.75% of
      the population within 45mins, and all of the population in an average response
      time of 18 mins included the rapid response HEMS model. CONCLUSIONS: HEMS base
      locations can be optimised based on either percentage of the population covered,
      or average response time to the entire population. We have also demonstrated a
      hybrid technique that optimizes response time for a given number of bases and
      minimum defined threshold of population coverage. Addition of specialized rapid
      response HEMS services to a system of multirole retrieval HEMS may reduce overall
      average response times by improving access in large urban areas.

PMID- 29037169
TI  - Left ventricular non-compaction cardiomyopathy with coronary artery anomaly
      complicated by ventricular tachycardia.
AB  - BACKGROUND: Non-compaction cardiomyopathy (NCCM) is characterized by prominent
      trabeculations, deep intertrabecular recesses, and a thick non-compacted
      endocardial myocardium. Prevalence in the general population remains unclear, but
      echocardiography series report 0.05%. During fetal development muscle fibers and
      trabeculae should compact into a solid myocardium and when this fails, NCCM
      occurs. The condition is genetic, even though acquired forms have been described.
      Worsening myocardial dysfunction may lead to heart failure and/or arrhythmias.
      CASE PRESENTATION: A 52-year-old man presented with heart failure. The diagnosis
      of NCCM was confirmed after echocardiography and cardiac magnetic resonance
      tomography. Interestingly, the angiogram revealed a coronary anomaly, in which
      the circumflex artery rose aberrantly from the right coronary artery. Due to left
      ventricular ejection fraction being less than 35% despite optimal pharmacological
      therapy, an implantable cardioverter defibrillator (ICD) was implanted and four
      years later a ventricular tachycardia was terminated by antitachycardia pacing.
      CONCLUSION: We describe a case of NCCM with a concomitant coronary anomaly, in
      which systolic myocardial dysfunction developed. The ICD subsequently terminated
      a life-threatening ventricular arrhythmia, which supports risk stratification
      based on low ejection fraction and possibly coronary anomaly.

PMID- 29037170
TI  - Multidisciplinary consensus on screening for, diagnosis and management of fetal
      growth restriction in the Netherlands.
AB  - BACKGROUND: Screening for, diagnosis and management of intrauterine growth
      restriction (IUGR) is often performed in multidisciplinary collaboration.
      However, variation in screening methods, diagnosis and management of IUGR may
      lead to confusion. In the Netherlands two monodisciplinary guidelines on IUGR do
      not fully align. To facilitate effective collaboration between different
      professionals in perinatal care, we undertook a Delphi study with uniform
      recommendations as our primary result, focusing on issues that are not aligned or
      for which specifications are lacking in the current guidelines. METHODS: We
      conducted a Delphi study in three rounds. A purposively sampled selection of 56
      panellists participated: 27 representing midwife-led care and 29 obstetrician-led
      care. Consensus was defined as agreement between the professional groups on the
      same answer and among at least 70% of the panellists within groups. RESULTS: Per
      round 51 or 52 (91% - 93%) panellists responded. This has led to consensus on 27
      issues, leading to four consensus based recommendations on screening for IUGR in
      midwife-led care and eight consensus based recommendations on diagnosis and eight
      on management in obstetrician-led care. The multidisciplinary project group
      decided on four additional recommendations as no consensus was reached by the
      panel. No recommendations could be made about induction of labour versus
      expectant monitoring, nor about the choice for a primary caesarean section.
      CONCLUSIONS: We reached consensus on recommendations for care for IUGR within a
      multidisciplinary panel. These will be implemented in a study on the
      effectiveness and cost-effectiveness of routine third trimester ultrasound for
      monitoring fetal growth. Research is needed to evaluate the effects of
      implementation of these recommendations on perinatal outcomes. TRIAL
      REGISTRATION: NTR4367 .

PMID- 29037172
TI  - The impact of influenza on the health related quality of life in China: an EQ-5D
      survey.
AB  - BACKGROUND: Influenza causes considerable morbidity and mortality in China, but
      its impact on the health-related quality of life (HRQoL) has not been previously
      measured. METHODS: We conducted a retrospective telephone survey to assess the
      impact of influenza on the HRQoL among outpatients and inpatients using the
      EuroQoL EQ-5D-3 L instrument. Participants were individuals with laboratory
      confirmed influenza infection registered by the National Influenza-like-illness
      Surveillance Network in 2013. RESULTS: We interviewed 839 of 11,098 eligible
      influenza patients. After excluding those who were unable to complete the HRQoL
      for the registered influenza episode, 778 patients were included in the analysis.
      Both outpatients (n = 529) and inpatients (n = 249) most commonly reported
      problems with pain/discomfort (71.8% of outpatients and 71.9% of inpatients) and
      anxiety/depression (62.0% of outpatients and 75.1% of inpatients). For individual
      influenza outpatients, the mean health utility was 0.6142 (SD 0.2006), and the
      average quality adjusted life days (QALD) loss was 1.62 (SD 1.84) days. The HRQoL
      of influenza inpatients was worse (mean health utility 0.5851, SD 0.2197; mean
      QALD loss 3.51 days, SD 4.25) than that of outpatients (p < 0.05). The presence
      of underlying medical conditions lowered the HRQoL for both outpatients and
      inpatients (p < 0.05). CONCLUSIONS: Influenza illness had a substantial impact on
      HRQoL. QALD loss due to an acute influenza episode in younger children was
      comparable to that due to enterovirus A71-associated hand, foot and mouth
      disease. Our findings are key inputs into disease burden estimates and cost
      effectiveness evaluations of influenza-related interventions in China.

PMID- 29037171
TI  - PeakCaller: an automated graphical interface for the quantification of
      intracellular calcium obtained by high-content screening.
AB  - BACKGROUND: Intracellular calcium is an important ion involved in the regulation
      and modulation of many neuronal functions. From regulating cell cycle and
      proliferation to initiating signaling cascades and regulating presynaptic
      neurotransmitter release, the concentration and timing of calcium activity
      governs the function and fate of neurons. Changes in calcium transients can be
      used in high-throughput screening applications as a basic measure of neuronal
      maturity, especially in developing or immature neuronal cultures derived from
      stem cells. RESULTS: Using human induced pluripotent stem cell derived neurons
      and dissociated mouse cortical neurons combined with the calcium indicator Fluo
      4, we demonstrate that PeakCaller reduces type I and type II error in automated
      peak calling when compared to the oft-used PeakFinder algorithm under both basal
      and pharmacologically induced conditions. CONCLUSION: Here we describe
      PeakCaller, a novel MATLAB script and graphical user interface for the
      quantification of intracellular calcium transients in neuronal cultures.
      PeakCaller allows the user to set peak parameters and smoothing algorithms to
      best fit their data set. This new analysis script will allow for automation of
      calcium measurements and is a powerful software tool for researchers interested
      in high-throughput measurements of intracellular calcium.

PMID- 29037173
TI  - TaxMapper: an analysis tool, reference database and workflow for
      metatranscriptome analysis of eukaryotic microorganisms.
AB  - BACKGROUND: High-throughput sequencing (HTS) technologies are increasingly
      applied to analyse complex microbial ecosystems by mRNA sequencing of whole
      communities, also known as metatranscriptome sequencing. This approach is at the
      moment largely limited to prokaryotic communities and communities of few
      eukaryotic species with sequenced genomes. For eukaryotes the analysis is
      hindered mainly by a low and fragmented coverage of the reference databases to
      infer the community composition, but also by lack of automated workflows for the
      task. RESULTS: From the databases of the National Center for Biotechnology
      Information and Marine Microbial Eukaryote Transcriptome Sequencing Project, 142
      references were selected in such a way that the taxa represent the main lineages
      within each of the seven supergroups of eukaryotes and possess predominantly
      complete transcriptomes or genomes. From these references, we created an
      annotated microeukaryotic reference database. We developed a tool called
      TaxMapper for a reliably mapping of sequencing reads against this database and
      filtering of unreliable assignments. For filtering, a classifier was trained and
      tested on each of the following: sequences of taxa in the database, sequences of
      taxa related to those in the database, and random sequences. Additionally,
      TaxMapper is part of a metatranscriptomic Snakemake workflow developed to perform
      quality assessment, functional and taxonomic annotation and (multivariate)
      statistical analysis including environmental data. The workflow is provided and
      described in detail to empower researchers to apply it for metatranscriptome
      analysis of any environmental sample. CONCLUSIONS: TaxMapper shows superior
      performance compared to standard approaches, resulting in a higher number of true
      positive taxonomic assignments. Both the TaxMapper tool and the workflow are
      available as open-source code at Bitbucket under the MIT license:
      https://bitbucket.org/dbeisser/taxmapper and as a Bioconda package:
      https://bioconda.github.io/recipes/taxmapper/README.html .

PMID- 29037174
TI  - Vitamin D supplementation as a potential cause of U-shaped associations between
      vitamin D levels and negative health outcomes: a decision tree analysis for risk
      of frailty.
AB  - BACKGROUND: A recent controversy in vitamin D research is a "U-shaped
      association", with elevated disease risks at both high and low 25-hydroxyvitamin
      D (25 (OH) D) levels. METHODS: This is a cross-sectional study of 238 male
      nursing home veterans in Hawaii. Classification and regression tree (CART)
      analysis identified groups based on 25 (OH) D and vitamin D supplementation for
      frailty risk. Characteristics were examined and compared across the groups using
      logistic regression and receiver operating characteristic (ROC) curve analyses.
      RESULTS: CART analysis identified three distinct groups: vitamin D supplement
      users (n = 86), non-users with low vitamin D (n = 55), and non-users with high
      vitamin D (n = 97). Supplement users were the most frail, but had high mean 25
      (OH) D of 26.6 ng/mL, which was compatible with 27.1 ng/mL in non-users with high
      vitamin D, while mean 25 (OH) D of non-users with low vitamin D was 11.7 ng/mL.
      Supplement users and non-users with low vitamin D were significantly more likely
      to be frail (odds ratio (OR) = 9.90, 95% CI = 2.18-44.86, p = 0.003; OR = 4.28,
      95% CI = 1.44-12.68, p = 0.009, respectively), compared with non-users with low
      vitamin D. ROC curve analysis showed the three groups significantly predicted
      frailty (area under the curve = 0.73), with sensitivity of 64.4% and specificity
      of 76.7%, while 25 (OH) D did not predict frailty. CONCLUSIONS: In these nursing
      home veterans, vitamin D supplement users were the most frail but with high 25
      (OH) D. This can potentially be a cause of U-shaped associations between vitamin
      D levels and negative health outcomes.

PMID- 29037175
TI  - A ten-year study of midwife-led care at an Austrian tertiary care center: a
      retrospective analysis with special consideration of perineal trauma.
AB  - BACKGROUND: In contrast to other countries, Austria rarely offers alternative
      models to medical led-care. In an attempt to improve the facilities, a midwife
      led care service was incorporated within the Department of Obstetrics and
      Fetomaternal Medicine. The aim of the present study was to analyze the maternal
      and neonatal outcomes of this approach. METHODS: Over a 10-years period, a total
      of 2123 low-risk women receiving midwife-led care were studied. Among these
      women, 148 required obstetric referral. Age- and parity matched low-risk women
      with spontaneous vaginal birth overseen by an obstetrician-led team were used as
      controls to ensure comparability of data. RESULTS: Midwife-led care management
      demonstrated a significant decrease in interventions, including oxytocin use (p <
      0.001), medical pain relief (p < 0.001), and artificial rupture of membranes
      (ARM) (p < 0.01) as well as fewer episiotomies (p < 0.001), as compared with
      obstetrician-led care. Moreover, no negative effects on maternal or neonatal
      outcomes were observed. The mean length of the second stage of labor, rate of
      perineal laceration and APGAR scores did not differ significantly between the
      study groups (p > 0.05). Maternal age (p < 0.01), head diameter (p < 0.001),
      birth weight (p < 0.001) and the absence of midwife-led care (p < 0.05) were
      independent risk factors for perineal trauma. The overall referral rate was low
      (7%) and was most commonly caused by pathologic cardiotocography (CTG) and
      prolonged first- and second-stage of labor. Most referred mothers nevertheless
      had spontaneous deliveries (77%), and there were low rates of vaginal operative
      deliveries and cesarean sections (vacuum extraction, 16%; cesarean section, 7%).
      CONCLUSIONS: The present study confirmed that midwife-led care confers important
      benefits and causes no adverse outcomes for mother and child. The favorable
      obstetrical outcome clearly highlights the importance of the selection of
      obstetric care, on the basis of previous risk assessment. We therefore fully
      support the recommendation that midwife-led care be offered to all low-risk women
      and that mothers should be encouraged to use this option. However, to increase
      the numbers of midwife-led care deliveries in Austria in the future, it will be
      necessary to expand this care model and to establish new midwife-led care units
      within hospital facilities.

PMID- 29037176
TI  - The association between high birth weight and the risks of childhood CNS tumors
      and leukemia: an analysis of a US case-control study in an epidemiological
      database.
AB  - BACKGROUND: High birth weight (BW), 4000 g or larger, is an established risk
      factor for childhood leukemia. However, its association with central nervous
      system (CNS) tumor risk is yet unclear. The present study examined it, analyzing
      data obtained from a case-control study conducted among three states from the US.
      The association with childhood leukemia risk was also further examined. METHODS:
      In this study, a data set provided by the Comprehensive Epidemiologic Data
      Resource was analyzed with an official permission. The original case-control
      study was conducted to examine the association between paternal preconception
      exposure to ionizing radiation and childhood cancer risk. Cases with childhood
      cancer were mainly ascertained from local hospitals, and controls were selected,
      matched with birth year (1-year category), county of residence, sex, ethnicity
      and maternal age (+/-2 years). Since the ID numbers were unavailable,
      conventional logistic analyses were conducted adjusting for those matching
      variables except for the county of residence. In addition to those variables,
      gestational age, age at diagnosis and study sites as covariables were included in
      the logistic models. RESULTS: Analyzed subjects were 72 CNS tumor cases, 124
      leukemia cases and 822 controls born from 1945 to 1989. The odds ratios (ORs) of
      CNS tumor risk for children with low BWs (<2500 g) and high BWs (>4000 g) were
      2.0 (95% confidence interval [CI]) = 0.7, 5.9) and 2.5 (95%CI = 1.2, 5.2)],
      respectively. When high-BW children were restricted to those who were large for
      gestational age (LGA), the OR for high-BW children remained similar (OR = 2.7;
      95%CI = 1.1, 6.2). On the other hand, the ORs of leukemia risk for children with
      low and high BWs were 0.8 (95%CI = 0.2, 3.0) and 1.4 (95%CI = 0.7, 2.6),
      respectively. In the normal range of BW (2500-4000 g), higher BW was positively
      associated with CNS tumor risk (beta = 0.0011, p for trend = 0.012). However, the
      association with leukemia risk was not significant (beta = -0.0002, p for trend =
      0.475). CONCLUSION: High-BW and LGA children had an elevated childhood CNS tumor
      risk. In the normal BW range, the BW itself was positively related to CNS tumor
      risk. No significant association between BW and childhood leukemia risk was
      observed in this study.

PMID- 29037178
TI  - Feasibility of a Smartphone website to support antenatal Perineal massage in
      pregnant women.
AB  - BACKGROUND: In Japan, 85% of pregnant women do not practice antenatal perineal
      massage. Therefore, we developed a smartphone website to support the practice of
      antenatal perineal massage. The purpose of the present study was to evaluate the
      feasibility of our smartphone website. METHODS: Pregnant women were recruited at
      five hospitals or clinics in Tokyo, Japan. Participants assigned to the
      smartphone website group (n = 74) were asked to register on the smartphone
      website. After completing registration, they could login and use all the contents
      of the website. After giving birth, participants completed a 5-item questionnaire
      evaluating the acceptability of the smartphone website. Participants assigned to
      the leaflet group (n = 71) received a leaflet on antenatal perineal massage and
      completed a similar 4-item questionnaire evaluating the leaflet. Data were
      collected from April 2014 to November 2014. Data analysis was performed using chi
      square and t-tests to analyze responses to close-ended questions, and content
      analysis was conducted to analyze responses of open-ended questions. RESULTS: In
      the smartphone website group, 9 women (12.2%) did not register on the smartphone
      website. Approximately 80% of the women who responded indicated that the
      smartphone site was easy to understand and useful for practicing antenatal
      perineal massage. In the smartphone website group, the reply rate for reporting
      the frequency of massage was 43.6%. Although the ratings and frequency at which
      the material was accessed tended to be higher in the smartphone website group
      than in the leaflet group, there were no significant differences. CONCLUSIONS:
      Most pregnant women in the smartphone website group provided a favorable
      evaluation for the smartphone website. However, some participants had suggestions
      for improvement, which need to be incorporated in a revised version of the
      website. Therefore, the present study's results demonstrate the feasibility of a
      smartphone website to support the practice of antenatal perineal massage, and
      they may aid in the development of similar web-based educational material for
      pregnant women. TRIAL REGISTRATION: This trial was registered with the UMIN
      Clinical Trials Registry ( UMIN000013979 ) on May 16, 2014.

PMID- 29037177
TI  - Development and psychometric testing of a theory-based tool to measure self-care
      in diabetes patients: the Self-Care of Diabetes Inventory.
AB  - BACKGROUND: Self-care is essential for patients with diabetes mellitus. Both
      clinicians and researchers must be able to assess the quality of that self-care.
      Available tools have various limitations and none are theoretically based. The
      aims of this study were to develop and to test the psychometric properties of a
      new instrument based on the middle range-theory of self-care of chronic illness:
      the Self-Care of Diabetes Inventory (SCODI). METHODS: Forty SCODI items (5 point
      Likert type scale) were developed based on clinical recommendations and grouped
      into 4 dimensions: self-care maintenance, self-care monitoring, self-care
      management and self-care confidence based on the theory. Content validity was
      assessed by a multidisciplinary panel of experts. A multi-centre cross-sectional
      study was conducted in a consecutive sample of 200 type 1 and type 2 diabetes
      patients. Dimensionality was evaluated by exploratory factor analyses.
      Multidimensional model based reliability was estimated for each scale. Multiple
      regression models estimating associations between SCODI scores and glycated
      haemoglobin (HbA1c), body mass index, and diabetes complications, were used for
      construct validity. RESULTS: Content validity ratio was 100%. A multidimensional
      structure emerged for the 4 scales. Multidimensional model-based reliabilities
      were between 0.81 (maintenance) and 0.89 (confidence). Significant associations
      were found between self-care maintenance and HbA1c (p = 0.02) and between self
      care monitoring and diabetes complications (p = 0.04). Self-care management was
      associated with BMI (p = 0.004) and diabetes complications (p = 0.03). Self-care
      confidence was a significant predictor of self-care maintenance, monitoring and
      management (all p < 0.0001). CONCLUSION: The SCODI is a valid and reliable
      theoretically-grounded tool to measure self-care in type 1 and type 2 DM
      patients.

PMID- 29037179
TI  - Piloting a mHealth intervention to improve newborn care awareness among rural
      Cambodian mothers: a feasibility study.
AB  - BACKGROUND: Globally, the World Health Organization reports that the chances of a
      child dying is highest in the first month of life, the neonatal period. The
      neonatal mortality rate in Cambodia is 18 per 1000 live births. In the province
      of Kampong Chhnang, that rate is the fifth highest among the 24 provinces of
      Cambodia at 27 per 1000 live births. We piloted a project to determine the
      feasibility of using a mHealth intervention (the use of mobile devices to improve
      health outcomes) to increase mothers' awareness about neonatal care and promote
      the government policy 'Safe Motherhood Protocols for Health Centres' which are in
      line with WHO recommendations for neonatal care. METHODS: Between September and
      December 2013, we piloted an Interactive Voice Response system that sent pre
      recorded messages to mothers of newborns using the theme 'It takes a village to
      raise a baby'. Four hundred fifty-five mothers were registered onto this program
      and the intervention involved delivering seven periodic 60 to 90 s voice messages
      directly to the mobile phones of these mothers from day three of their neonate's
      life to day 28. An evaluation of the pilot was conducted in December 2013. One
      hundred twenty-nine mothers were randomly selected from the 455 registered
      mothers and interviewed using a quantitative questionnaire. We also held two
      focus group discussions with three mothers and seven health workers. RESULTS:
      Quantitative and qualitative results of 126 respondents were included for
      analysis. They indicate that the intervention was well accepted. Seventy-one
      percent of respondents reported that they would recommend the intervention to
      other mothers, and 83% reported that they would be willing to pay for the
      service. CONCLUSIONS: This type of mHealth intervention is an acceptable and
      feasible way of promoting the awareness of newborn care to rural Cambodian
      mothers.

PMID- 29037180
TI  - Comparison of improved range of motion between cam-type femoroacetabular
      impingement and borderline developmental dysplasia of the hip -evaluation by
      virtual osteochondroplasty using computer simulation.
AB  - BACKGROUND: While cam resection is essential to achieve a good clinical result
      with respect to femoroacetabular impingement (FAI), it is unclear whether it
      should also be performed in cases of borderline developmental dysplasia of the
      hip (DDH) with a cam deformity. The aim of this study was to evaluate
      improvements in range of motion (ROM) in cases of cam-type FAI and borderline DDH
      after virtual osteochondroplasty using a computer impingement simulation.
      METHODS: Thirty-eight symptomatic hips in 31 patients (11male and 20 female)
      diagnosed with cam-type FAI or borderline DDH were analyzed. There were divided
      into a cam-type FAI group (cam-FAI group: 15 hips), borderline DDH without cam
      group (DDH W/O cam group: 12 hips), and borderline DDH with cam group (DDH W/ cam
      group: 11 hips). The bony impingement point on the femoral head-neck junction at
      90 degrees  flexion and maximum internal rotation of the hip joint was identified
      using ZedHip(r) software. Virtual osteochondroplasty of the impingement point was
      then performed in all cases. The maximum flexion angle and maximum internal
      rotation angle at 90 degrees  flexion were measured before and after virtual
      osteochondroplasty at two resection ranges (i.e., slight and sufficient).
      RESULTS: The mean improvement in the internal rotation angle in the DDH W/ cam
      group after slight resection was significantly greater than that in the DDH W/O
      cam group (P = 0.046). Furthermore, the mean improvement in the internal rotation
      angle in the DDH W/ cam and cam-FAI groups after sufficient resection was
      significantly greater than that in the DDH W/O cam group (DDH W/ cam vs DDH W/O
      cam: P = 0.002, cam-FAI vs DDH W/O cam: P = 0.043). CONCLUSION: Virtual
      osteochondroplasty resulted in a significant improvement in internal rotation
      angle in DDH W/ cam group but not in DDH W/O cam group. Thus, borderline DDH
      cases with cam deformity may be better to consider performing osteochondroplasty.

PMID- 29037181
TI  - The MOVE-trial: Monocryl(r) vs. Vicryl RapideTM for skin repair in mediolateral
      episiotomies: a randomized controlled trial.
AB  - BACKGROUND: Previous studies have shown that complaints after episiotomy repair
      depend on the method and material used for repair. The objective of our study was
      to determine which of two frequently used suture materials, Monocryl(r)
      (poliglecaprone 25) and Vicryl RapideTM (polyglactin 910), is superior for
      intracutaneous closure of the skin in mediolateral episiotomies. METHODS: In a
      randomized controlled trial performed in a teaching hospital in the Netherlands
      between 2010 and 2013 250 primiparous women with uncomplicated mediolateral
      episiotomies were randomly allocated to intracutaneous skin closure with either
      Monocryl(r) or Vicryl RapideTM. All other layers were sutured with Vicryl 2-0 and
      Vicryl 0 in both groups. Pain scores and complications were documented using
      questionnaires during the first three months post partum. The primary outcome was
      pain 10 days after delivery in sitting position established by Visual Analogous
      Scale (VAS). Secondary outcomes were pain scores at different time points and
      reported complications such as infections, dehiscence and dyspareunia one day, 10
      days, six weeks and three months after delivery. RESULTS: Of 250 allocated women
      54% returned questionnaires. No statistical difference was found between both
      groups for the primary outcome (VAS 2,8 (95% CI 2,18-3,44) vs. VAS 2,5 (95% CI
      2,00-2,98), p = 0,43). With regard to secondary outcomes only self-reported
      dehiscence was significantly different, favouring Monocryl(r) (10% vs. 25%, p =
      0.016). CONCLUSIONS: Use of Monocryl(r) 3-0 and Vicryl RapideTM 3-0 for
      intracutaneous closure of the skin after mediolateral episiotomy leads to equal
      pain scores ten days after delivery and therefore both materials may be
      considered for this use. Monocryl(r) 3-0 might be favourable over Vicryl RapideTM
      3-0 due to less self-reported dehiscence after intracutaneous closure of the skin
      in mediolateral episiotomies. TRIAL REGISTRATION: The trial was retrospectively
      registered under trial nr. ISRCTN29869308 on 20-04-2016.

PMID- 29037182
TI  - Ideas, actors and institutions: lessons from South Australian Health in All
      Policies on what encourages other sectors' involvement.
AB  - BACKGROUND: This paper examines the extent to which actors from sectors other
      than health engaged with the South Australian Health in All Policies (HiAP)
      initiative, determines why they were prepared to do so and explains the
      mechanisms by which successful engagement happened. This examination applies
      theories of policy development and implementation. METHODS: The paper draws on a
      five year study of the implementation of HiAP comprising document analysis, a log
      of key events, detailed interviews with 64 policy actors and two surveys of
      public servants. RESULTS: The findings are analysed within an institutional
      policy analysis framework and examine the extent to which ideas, institutional
      factors and actor agency influenced the willingness of actors from other sectors
      to work with Health sector staff under the HiAP initiative. In terms of ideas,
      there was wide acceptance of the role of social determinants in shaping health
      and the importance of action to promote health in all government agencies. The
      institutional environment was initially supportive, but support waned over the
      course of the study when the economy in South Australia became less buoyant and a
      health minister less supportive of health promotion took office. The existence of
      a HiAP Unit was very helpful for gaining support from other sectors. A new Public
      Health Act offered some promise of institutionalising the HiAP approach and
      ideas. The analysis concludes that a key factor was the operation of a supportive
      network of public servants who promoted HiAP, including some who were senior and
      influential. CONCLUSIONS: The South Australian case study demonstrates that
      despite institutional constraints and shifting political support within the
      health sector, HiAP gained traction in other sectors. The key factors that
      encouraged the commitment of others sectors to HiAP were the existence of a
      supportive, knowledgeable policy network, political support, institutionalisation
      of the ideas and approach, and balancing of the economic and social goals of
      government.

PMID- 29037183
TI  - Robot-assisted laparoscopic reconstructed management of multiple aneurysms in
      renal artery primary bifurcations: a case report and literature review.
AB  - BACKGROUND: Renal artery aneurysm (RAA) is rare and its incidence in the general
      population remains elusive. There have been few reports on the repair of multiple
      aneurysms conducted with the Da Vinci robot-assisted surgical platform (Intuitive
      Surgical Inc., Sunnyvale, CA, USA), especially for those located in renal artery
      primary bifurcations. CASE PRESENTATION: We report our experience in the surgical
      management of two expanding right-sided RAAs in a 64-year-old man using a robot
      assisted laparoscopic approach. Two aneurysms were located in renal artery
      primary bifurcations, whose diameter was 1.8 and 1.2 cm. The aneurysms were
      resected and the renal artery branch reconstructed by in situ arteriorrhaphy. The
      operation lasted for 2 h and 35 min with a warm ischemia time of 26 min and
      estimated blood loss of 150 ml. The hospital stay was 6 days. The computed
      tomography (CT) scan performed 2 months after the surgery showed resolution of
      the aneurysms. Additionally, split renal function indicated the preservation of
      right renal function in the follow-up period. CONCLUSIONS: The robot-assisted
      laparoscopic procedure is a safe and effective surgical technique, which may be
      considered as an alternative to open surgery for complex multiple RAAs in the
      future.

PMID- 29037184
TI  - Low back pain and causative movements in pregnancy: a prospective cohort study.
AB  - BACKGROUND: Low back pain (LBP) during pregnancy might be strongly related to
      posture and movements of the body, and its management is a clinically important
      issue. The purpose of this study was to investigate the activities related to LBP
      during pregnancy. METHODS: Participants included 275 women before 12 weeks of
      pregnancy. The women were evaluated at 12, 24, 30, and 36 weeks of pregnancy. The
      intensity of LBP was assessed using the Numerical Rating Scale (NRS). Movements
      related to LBP were investigated by free descriptive answers. Descriptive
      statistics were used to compile the movements that pregnant women thought induced
      LBP at each evaluation. Subsequently, a linear regression analysis was performed
      to evaluate the degree of association of certain movements with LBP using the
      data of participants who had LBP. The intensity of LBP (NRS score) was specified
      as the dependent variable, the movements that were related to pain were specified
      as the independent variables at the analysis. A significance threshold was set at
      0.05. RESULTS: The final sample used in the analyses was 254, 249, 258, and 245
      women at 12, 24, 30, and 36 weeks of pregnancy, respectively. There were 16 kinds
      of movements that induced LBP and all of them were daily activities rather than
      special movements that require extra task or effort. As pregnancy progressed,
      less number of participants attributed pain to a specific movement. At all
      evaluations, movements, especially sitting up, standing up from a chair, and
      tossing and turning were thought to be related to LBP. Furthermore, standing up
      from a chair and tossing and turning were significantly related to LBP throughout
      the pregnancy. In contrast, lying down and sitting up were significantly related
      to LBP but the relationship did not continue till late pregnancy. CONCLUSIONS:
      Daily routine activity is related to LBP during pregnancy. These results suggest
      that recommendations for pregnant women about basic physical movements, such as
      ways of standing up that reduce the load on the body might be useful in the
      management of LBP.

PMID- 29037185
TI  - Research involvement among undergraduate health sciences students: a cross
      sectional study.
AB  - BACKGROUND: The development of research capacity among undergraduates is an
      important intervention in countering the documented decrease in medical and
      health sciences researchers. The literature on undergraduate research generally
      emanates from smaller scale studies that have been conducted in high income
      countries, with a focus on medical students. This cross-sectional study was
      conducted in a Sub-Saharan country, included a population of medical and allied
      health professions (AHP) students, and aimed to improve our understanding of the
      factors influencing undergraduate student research. METHODS: A questionnaire was
      distributed to all students enrolled in an undergraduate programme at the Faculty
      of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
      (including Medicine and four AHP programmes). Data was collected on a number of
      demographic characteristics and on 3 major outcome-themes: "voluntary research
      involvement", "self-perceived research competence" and "future research
      participation". Associations between characteristics and outcome themes were
      explored. RESULTS: In total, 1815 students participated in the study (response
      rate 80.2%). Of all the demographic variables, discipline (AHP programmes vs.
      Medicine), male gender and prior undergraduate experience in a science degree
      were significantly associated with voluntary research involvement. Significantly
      higher levels of self-perceived research competence and greater interest in
      future research participation, were seen among participants from AHP programmes;
      males; and those with previous or current voluntary research involvement.
      Ethnicity and geographic background were not significantly associated with any of
      our outcomes. CONCLUSIONS: Our results offer important new evidence in support of
      the imperative to diversify the research work-force, in Sub-Saharan Africa and
      globally. Enhanced efforts aimed at achieving better academic representation in
      terms of gender, ethnicity, geographical and socio-economic backgrounds are
      strengthened by the findings of this study. Potential student researchers
      represent an important group amenable to further intervention. Further research
      may be required to explore the factors that determine the progression from
      interest to future participation in research.

PMID- 29037186
TI  - Comparison of serum markers for muscle damage, surgical blood loss, postoperative
      recovery, and surgical site pain after extreme lateral interbody fusion with
      percutaneous pedicle screws or traditional open posterior lumbar interbody
      fusion.
AB  - BACKGROUND: The benefits of extreme lateral interbody fusion (XLIF) as a
      minimally invasive lumbar spinal fusion treatment for lumbar degenerative
      spondylolisthesis have been unclear. We sought to evaluate the invasiveness and
      tolerability of XLIF with percutaneous pedicle screws (PPS) compared with
      traditional open posterior lumbar interbody fusion (PLIF). METHODS: Fifty-six
      consecutive patients underwent open PLIF and 46 consecutive patients underwent
      single-staged treatment with XLIF with posterior PPS fixation for degenerative
      lumbar spondylolisthesis, and were followed up for a minimum of 1 year. We
      analyzed postoperative serum makers for muscle damage and inflammation,
      postoperative surgical pain, and performance status. A Roland-Morris Disability
      Questionnaire (RDQ) and Oswestry Disability Index (ODI) were obtained at the time
      of hospital admission and 1 year after surgery. RESULTS: Intraoperative blood
      loss (51 +/- 41 ml in the XLIF/PPS group and 206 +/- 191 ml in the PLIF group),
      postoperative WBC counts and serum CRP levels in the XLIF/PPS group were
      significantly lower than in the PLIF group. Postoperative serum CK levels were
      significantly lower in the XLIF/PPS group on postoperative days 4 and 7.
      Postoperative recovery of performance was significantly greater in the XLIF/PPS
      group than in the PLIF group from postoperative days 2 to 7. ODI and visual
      analog scale (VAS) score (lumbar) 1 year after surgery were significantly lower
      in the XLIF/PPS group compared with the PLIF group. CONCLUSIONS: The XLIF/PPS
      procedure is advantageous to minimize blood loss and muscle damage, with
      consequent earlier recovery of daily activities and reduced incidence of low back
      pain after surgery than with the open PLIF procedure.

PMID- 29037187
TI  - Designing equitable workplace dietary interventions: perceptions of intervention
      deliverers.
AB  - BACKGROUND: Workplaces are a good setting for interventions that aim to support
      workers in achieving a healthier diet and body weight. However, little is known
      about the factors that impact on the feasibility and implementation of these
      interventions, and how these might vary by type of workplace and type of worker.
      The aim of this study was to explore the views of those involved in commissioning
      and delivering the Better Health at Work Award, an established and evidence-based
      workplace health improvement programme. METHODS: One-to-one semi-structured
      interviews were conducted with 11 individuals in North East England who had some
      level of responsibility for delivering workplace dietary interventions.
      Interviews were transcribed verbatim and analysed using thematic framework
      analysis. RESULTS: A number of factors were felt to promote the feasibility and
      implementation of interventions. These included interventions that were cost
      neutral (to employee and employer), unstructured, involved colleagues for
      support, took place at lunchtimes, and were well-advertised and communicated via
      a variety of media. Offering incentives, not necessarily monetary, was perceived
      to increase recruitment rates. Factors that militate against feasibility and
      implementation of interventions included worksites that were large in size and
      remote, working patterns including shifts and working outside of normal working
      hours that were not conducive to workers being able to access intervention
      sessions, workplaces without appropriate provision for healthy food on site, and
      a lack of support from management. CONCLUSIONS: Intervention deliverers perceived
      that workplace dietary interventions should be equally and easily accessible (in
      terms of cost and timing of sessions) for all staff, regardless of their job
      role. Additional effort should be taken to ensure those staff working outside
      normal working hours, and those working off-site, can easily engage with any
      intervention, to avoid the risk of intervention-generated inequalities (IGIs).

PMID- 29037189
TI  - Methodological study to evaluate the psychometric properties of FACIT-CD in a
      sample of Brazilian women with cervical intraepithelial neoplasia.
AB  - BACKGROUND: The occurrence of cervical intraepithelial neoplasia (CIN) is
      associated with changes in health-related quality of life, including
      psychological factors, such as fear and shame, and changes in sexuality and
      sexual satisfaction, such as decreased sexual desire and frequency of sexual
      intercourse. Personal relationships are the most affected because CIN is sexually
      transmitted and many women tend to blame their partner for disease transmission.
      The aim of this study was to evaluate the psychometric properties of the FACIT-CD
      questionnaire in Brazilian women diagnosed with CIN. METHODS: The properties of
      the FACIT-CD questionnaire were tested on a sample of 439 women seen at the
      Department of Prevention of Barretos Cancer Hospital, including 329 patients who
      were diagnosed with CIN and 110 women who were not diagnosed with the disease.
      The analysed parameters included internal consistency (Cronbach's alpha),
      reproducibility (intraclass correlation coefficient), structural validity,
      convergent validity (correlation with the SF-12 and EORTC QLQ-CX24
      questionnaires), discriminant validity (according to disease status, and self
      rating of health), sensitivity, and responsiveness. RESULTS: The Cronbach alpha
      values of the FACIT-CD scales were higher than 0.70 with the exception of the
      relationship scale (0.66). The FACIT-CD reproducibility was satisfactory, with
      variation in the intraclass correlation coefficients ranging between 0.50 and
      0.83, although the 95% confidence interval (CI) was lower than 0.40 (0.33-0.64)
      on the treatment satisfaction scale. Regarding structural validity, only one item
      on the physical well-being scale was not kept in the original domain. The
      expected correlations between the FACIT-CD and SF-12 were not confirmed, whereas
      the correlations between the FACIT-CD and EORTC QLQ-CX24 were confirmed. The
      questionnaire was able to discriminate the groups according to disease status and
      self-rating of health. The sensitivity was low for the relationship scale and
      moderate for the other scales. The responsiveness of the FACIT-CD questionnaire
      varied between the groups that denominate the self-perception of health as no
      change, improvement or worsening. CONCLUSION: Our results are encouraging and
      indicate that the FACIT-CD questionnaire is a promising tool for the analysis of
      the quality of life of women with CIN.

PMID- 29037190
TI  - Do mobile clinics provide high-quality antenatal care? A comparison of care
      delivery, knowledge outcomes and perception of quality of care between fixed and
      mobile clinics in central Haiti.
AB  - BACKGROUND: Antenatal care (ANC) is an important health service for women in
      developing countries, with numerous proven benefits. Global coverage of ANC has
      steadily increased over the past 30 years, in part due to increased community
      based outreach. However, commensurate improvements in health outcomes such as
      reductions in the prevalence of maternal anemia and infants born small-for
      gestational age have not been achieved, even with increased coverage, indicating
      that quality of care may be inadequate. Mobile clinics are one community-based
      strategy used to further improve coverage of ANC, but their quality of care
      delivery has rarely been evaluated. METHODS: To determine the quality of care of
      ANC in central Haiti, we compared adherence to national guidelines between fixed
      and mobile clinics by performing direct observations of antenatal care
      consultations and exit interviews with recipients of care using a multi-stage
      random sampling procedure. Outcome variables were eight components of care, and
      women's knowledge and perception of care quality. RESULTS: There were significant
      differences in the predicted proportion or probability of recommended services
      for four of eight care components, including intake, laboratory examinations,
      infection control, and supplies, iron folic acid supplements and Tetanus Toxoid
      vaccine provided to women. These care components were more likely performed in
      fixed clinics, except for distribution of supplies, iron-folic acid supplements,
      and Tetanus Toxoid vaccine, more likely provided in mobile clinics. There were no
      differences between clinic type for the proportion of total physical exam
      procedures performed, health and communication messages delivered, provider
      communication or documentation. Women's knowledge about educational topics was
      poor, but women perceived extremely high quality of care in both clinic models.
      CONCLUSIONS: Although adherence to guidelines differed by clinic type for half of
      the care components, both clinics had a low percentage of overall services
      delivered. Efforts to improve provider performance and quality are therefore
      needed in both models. Mobile clinics must deliver high-quality ANC to improve
      health and nutrition outcomes.

PMID- 29037188
TI  - Epidemiology of cervical human papillomavirus (HPV) infection and squamous
      intraepithelial lesions (SIL) among a cohort of HIV-infected and uninfected
      Ghanaian women.
AB  - BACKGROUND: There is limited data in Ghana on the epidemiology of HPV and
      cervical neoplasia and their associations with HIV. This study aimed to compare
      among HIV-1 seropositive and HIV-seronegative Ghanaian women: (1) the prevalence,
      genotype distribution and risk factors associated with cervical HPV infection;
      and (2) the prevalence and risk factors associated with abnormal cervical
      cytology. METHODS: A comparative frequency-matched study was conducted in a
      systematic sample of women aged >=18 years attending HIV and general outpatient
      clinics in Cape Coast Teaching Hospital, Ghana. Participants were interviewed and
      cervical samples collected for HPV genotyping (Seegene Anyplex-II HPV28) and
      cytological testing. RESULTS: Overall, 333 women were recruited, 163 HIV-1
      seropositive and 170 HIV-seronegative women of mean age 43.8 years (SD +/-9.4))
      and 44.3 years (SD +/-12.8), respectively. The prevalence of 14 high-risk (hr)
      HPV genotypes was higher among HIV-1 seropositive women (65.6% vs. 30.2%, P <
      0.0001), as was proportion with multiple hr.-HPV infections (60.6% vs. 21.3%, P <
      0.0001). HPV35 was the most prevalent hr.-HPV genotype in both groups (11.9% and
      5.3%). The main factors associated with hr.-HPV infection were age for HIV
      positive women and circumcision status of main sexual partner for both HIV
      negative and positive women. Abnormal cervical cytology prevalence was higher
      among HIV-1 seropositive women (any SIL: 14.1% vs. 1.2%, P < 0.0001; low-grade
      SIL [LSIL]: 4.9% vs. 0.6%, P = 0.02; high-grade SIL: 1.8% vs. 0%, P = 0.07).
      Among HIV-1 seropositive women, number of pregnancies and CD4+ cell count were
      associated with LSIL+ cytology. There was strong association between LSIL+
      abnormalities and HPV35 (aOR = 4.7, 95%CI: 1.3-17.7, P = 0.02). CONCLUSIONS: HIV
      1 infected women bear significant burden of HPV infection and related disease.
      Prevention and screening programmes should be specifically deployed for this
      population in Ghana.

PMID- 29037191
TI  - Ascorbic acid alters cell fate commitment of human neural progenitors in a
      WNT/beta-catenin/ROS signaling dependent manner.
AB  - BACKGROUND: Improving the neuronal yield from in vitro cultivated neural
      progenitor cells (NPCs) is an essential challenge in transplantation therapy in
      neurological disorders. In this regard, Ascorbic acid (AA) is widely used to
      expand neurogenesis from NPCs in cultures although the mechanisms of its action
      remain unclear. Neurogenesis from NPCs is regulated by the redox-sensitive
      WNT/beta-catenin signaling pathway. We therefore aimed to investigate how AA
      interacts with this pathway and potentiates neurogenesis. METHODS: Effects of 200
      MUM AA were compared with the pro-neurogenic reagent and WNT/beta-catenin
      signaling agonist lithium chloride (LiCl), and molecules with antioxidant
      activities i.e. N-acetyl-L-cysteine (NAC) and ruthenium red (RuR), in
      differentiating neural progenitor ReNcell VM cells. Cells were supplemented with
      reagents for two periods of treatment: a full period encompassing the whole
      differentiation process versus an early short period that is restricted to the
      cell fate commitment stage. Intracellular redox balance and reactive oxygen
      species (ROS) metabolism were examined by flow cytometry using redox and ROS
      sensors. Confocal microscopy was performed to assess cell viability, neuronal
      yield, and levels of two proteins: Nucleoredoxin (NXN) and the WNT/beta-catenin
      signaling component Dishevelled 2 (DVL2). TUBB3 and MYC gene responses were
      evaluated by quantitative real-time PCR. DVL2-NXN complex dissociation was
      measured by fluorescence resonance energy transfer (FRET). RESULTS: In contrast
      to NAC which predictably exhibited an antioxidant effect, AA treatment enhanced
      ROS metabolism with no cytotoxic induction. Both drugs altered ROS levels only at
      the early stage of the differentiation as no changes were held beyond the
      neuronal fate commitment stage. FRET studies showed that AA treatment accelerated
      the redox-dependent release of the initial pool of DVL2 from its sequestration by
      NXN, while RuR treatment hampered the dissociation of the two proteins.
      Accordingly, AA increased WNT/beta-catenin signaling output i.e. MYC mRNA level,
      whereas RuR attenuated it. Moreover, AA improved neurogenesis as much as LiCl as
      both TUBB3-positive cell yield and TUBB3 mRNA level increased, while NAC or RuR
      attenuated neurogenesis. Markedly, the neurogenesis outputs between the short and
      the full treatment with either NAC or AA were found unchanged, supporting our
      model that neuronal yield is altered by events taking place at the early phase of
      differentiation. CONCLUSIONS: Our findings demonstrate that AA treatment elevates
      ROS metabolism in a non-lethal manner prior to the NPCs commitment to their
      neuronal fate. Such effect stimulates the redox-sensitive DVL2 activation and
      WNT/beta-catenin signaling response that would enhance the ensuing neuronal cell
      differentiation.

PMID- 29037192
TI  - Retroperitoneal ectopic pregnancy: a case report and review of the literature.
AB  - BACKGROUND: Retroperitoneal ectopic pregnancy (REP) is an extremely rare type of
      ectopic pregnancy, with a total of less than 20 cases reported in the English
      literature. However, failure to recognize REP may result in severe consequences.
      CASE PRESENTATION: We report a case of 32-year-old woman with REP. She had
      amenorrhea, left lower abdominal pain, but no vaginal bleeding. Her urine human
      chorionic gonadotropin (HCG) test was positive and blood HCG level was 1880 m
      international units per milliliter (mIU/mL). Transvaginal ultrasound sonography
      showed a left adnexal mass. Laparoscopy found an enlarged uterus, normal right
      uterine tube and ovary, and normal left uterine tube. The left ovary was partly
      covered by a blood clot, but appeared normal after removing the clot. There was a
      10-mm circular peritoneal defect located lateral to the left sacrocervical
      ligament, anterior to the left ovarian fossa, and next to the lower edge of the
      left broad ligament. The patient was diagnosed of having REP with the gestational
      tissues covered by the peritoneum. The REP was removed by laparoscopic surgery.
      Bleeding was stopped by bipolar coagulation and absorbable hemostatic cellulose.
      The patient recovered smoothly and was discharged on the next day after surgery.
      Her blood HCG returned to normal range 29 days after surgery. CONCLUSIONS: REP is
      very rare, but in any suspected case of ectopic pregnancy, caution must be paid
      to find signs of REP when the common sites of ectopic pregnancy do not have any
      positive findings.

PMID- 29037193
TI  - Molecular surveillance of pfhrp2 and pfhrp3 deletions in Plasmodium falciparum
      isolates from Mozambique.
AB  - BACKGROUND: Malaria programmes use Plasmodium falciparum histidine-rich protein-2
      (PfHRP2) based rapid diagnostic tests (RDTs) for malaria diagnosis. The deletion
      of this target antigen could potentially lead to misdiagnosis, delayed treatment
      and continuation of active transmission. METHODS: Plasmodium falciparum isolates
      (n = 1162) collected in Southern Mozambique were assessed by RDTs, microscopy
      and/or 18SrRNA qPCR. pfhrp2 and pfhrp3 deletions were investigated in isolates
      from individuals who were negative by RDT but positive by microscopy and/or qPCR
      (n = 69) using gene-specific PCRs, with kelch13 PCR as the parasite DNA control.
      RESULTS: Lack of pfhrp2 PCR amplification was observed in one of the 69 isolates
      subjected to molecular analysis [1.45% (95% CI 0.3-7.8%)]. CONCLUSIONS: The low
      prevalence of pfhrp2 deletions suggests that RDTs will detect the vast majority
      of the P. falciparum infections. Nevertheless, active surveillance for changing
      deletion frequencies is required.

PMID- 29037194
TI  - A posterior versus anterior debridement in combination with bone graft and
      internal fixation for lumbar and thoracic tuberculosis.
AB  - BACKGROUND: Surgery treatment is usually required for spinal tuberculosis. The
      aim of this study was to compare the clinical efficacy and outcomes of anterior
      and posterior surgical approach in combination with debridement, bone grafting,
      and internal fixation. METHODS: All patients with thoracic and lumbar
      tuberculosis who underwent either the anterior or posterior surgery in
      combination with debridement, bone grafting, and internal fixation from August
      2009 to August 2016 were reviewed retrospectively. RESULTS: A total of 186
      patients were recruited in the analyses, 37 of whom received the anterior
      approach and 149 treated with the posterior approach. In the entire study
      population, there was no statistically significant difference between the groups
      in terms of kyphosis Cobb's angle, VAS pain score, neurological status, operation
      duration, perioperative blood loss, and hospitalization days (p > 0.05). Good
      clinical outcomes were achieved in both treatment groups. In lumbar vertebra
      affected patients, the average preoperative kyphosis Cobb's angle was 8.7 +/-
      16.6 degrees  and - 5.6 +/- 16.0 degrees  for the anterior and posterior groups,
      respectively, which were corrected to - 3.3 +/- 13.2 degrees  and - 10.1 +/- 13.8
      degrees  after surgery. For thoracic vertebra-affected patients, the corrected
      kyphosis Cobb's angle was 8.1 +/- 9.7 degrees  and 10.3 +/- 6.5 degrees ,
      respectively. After surgery, 32.4% of patients in the anterior group and 48.3% of
      patients in the posterior group claimed no pain (p = 0.24), while 83.8 and 85.9%
      recovered to Frankel grade E, respectively (p = 0.85). CONCLUSIONS: The posterior
      debridement joint bone graft and internal fixation is an alternative procedure to
      treat lumbar and thoracic tuberculosis compared to the traditional anterior
      approach with similar clinical efficacy in terms of pain control, Cobb's angle,
      and neurological function. The posterior approach is sufficient for lesion
      debridement.

PMID- 29037195
TI  - Comparison between xCELLigence biosensor technology and conventional cell culture
      system for real-time monitoring human tenocytes proliferation and drugs
      cytotoxicity screening.
AB  - BACKGROUND: Local injections of anesthetics, NSAIDs, and corticosteroids for
      tendinopathies are empirically used. They are believed to have some cytotoxicity
      toward tenocytes. The maximal efficacy dosages of local injections should be
      determined. A commercial 2D microfluidic xCELLigence system had been developed to
      detect real-time cellular proliferation and their responses to different stimuli
      and had been used in several biomedical applications. The purpose of this study
      is to determine if human tenocytes can successfully proliferate inside
      xCELLigence system and the result has high correlation with conventional cell
      culture methods in the same condition. METHODS: First passage of human tenocytes
      was seeded in xCELLigence and conventional 24-well plates. Ketorolac
      tromethamine, bupivacaine, methylprednisolone, and betamethasone with different
      concentrations (100, 50, and 10% diluted of clinical usage) were exposed in both
      systems. Gene expression of type I collagen, type III collagen, tenascin-C,
      decorin, and scleraxis were compared between two systems. RESULTS: Human
      tenocytes could proliferate both in xCELLigence and conventional cell culture
      systems. Cytotoxicity of each drug revealed dose-dependency when exposed to
      tenocytes in both systems. Significance was found between groups. All the four
      drugs had comparable cytotoxicity in their 100% concentration. When 50%
      concentration was used, betamethasone had a relatively decreased cytotoxicity
      among them in xCELLigence but not in conventional culture. When 10% concentration
      was used, betamethasone had the least cytotoxicity. Strong and positive
      correlation was found between cell index of xCELLigence and result of WST-1 assay
      (Pearson's correlation [r] = 0.914). Positive correlation of gene expression
      between tenocytes in xCELLigence and conventional culture was also observed. Type
      I collagen: [r] = 0.823; type III collagen: [r] = 0.899; tenascin-C: [r] = 0.917;
      decorin: [r] = 0.874; and scleraxis: [r] = 0.965. CONCLUSIONS: Human tenocytes
      could proliferate inside xCELLigence system. These responses varied when
      tenocytes were exposed to different concentrations of ketorolac tromethamine,
      bupivacaine, methylprednisolone, and betamethasone. The result of cell
      proliferation and gene expression of tenocytes in both xCELLigence and
      conventional culture system is strongly correlated. CLINICAL RELEVANCE:
      xCELLigence culture system may replace conventional cell culture, which made real
      time tenocyte proliferation monitoring possible.

PMID- 29037196
TI  - Unmet clinical needs and burden in Angelman syndrome: a review of the literature.
AB  - BACKGROUND: Angelman syndrome (AS) is a rare disorder with a relatively well
      defined phenotype. Despite this, very little is known regarding the unmet
      clinical needs and burden of this condition, especially with regard to some of
      the most prevalent clinical features-movement disorders, communication
      impairments, behavior, and sleep. MAIN TEXT: A targeted literature review using
      electronic medical databases (e.g., PubMed) was conducted to identify recent
      studies focused on specific areas of the AS phenotype (motor, communication,
      behavior, sleep) as well as epidemiology, diagnostic processes, treatment, and
      burden. 142 articles were reviewed and summarized. Findings suggest significant
      impairment across the life span in all areas of function. While some issues may
      resolve as individuals get older (e.g., hyperactivity), others become worse
      (e.g., movement disorders, aggression, anxiety). There are no treatments focused
      on the underlying etiology, and the symptom-based therapies currently prescribed
      do not have much, if any, empirical support. CONCLUSIONS: The lack of
      standardized treatment protocols or approved therapies, combined with the
      severity of the condition, results in high unmet clinical needs in the areas of
      motor functioning, communication, behavior, and sleep for individuals with AS and
      their families.

PMID- 29037197
TI  - Human epicardial adipose tissue-derived and circulating secreted frizzled-related
      protein 4 (SFRP4) levels are increased in patients with coronary artery disease.
AB  - BACKGROUND: Previous studies have demonstrated that secreted frizzled-related
      protein 4 (SFRP4) is associated with impaired glucose and triglyceride metabolism
      in patients with stable coronary artery disease. In the present study, we
      investigated human epicardial adipose tissue (EAT)-derived and circulating SFRP4
      levels in patients with coronary artery disease (CAD). METHODS: Plasma samples
      and adipose biopsies from EAT and subcutaneous adipose tissue (SAT) were
      collected from patients with CAD (n = 40) and without CAD (non-CAD, n = 30)
      during elective cardiac surgery. The presence of CAD was identified by coronary
      angiography. SFRP4 mRNA and protein expression levels in adipose tissue were
      detected by quantitative real-time PCR and immunohistochemistry, respectively.
      Plasma SFRP4 concentrations were measured by an enzyme-linked immunosorbent assay
      (ELISA). Correlation analysis and multivariate linear regression analysis were
      used to determine the association of SFRP4 expression with atherosclerosis as
      well as clinical risk factors. RESULTS: SFRP4 mRNA and protein expression levels
      were significantly lower in EAT than in paired SAT in patients with and without
      CAD (all P < 0.05). Compared to non-CAD patients, CAD patients had higher SFRP4
      expression levels in EAT (both mRNA and protein levels) and in plasma.
      Multivariate linear regression analysis showed that CAD was an independent
      predictor of SFRP4 expression levels in EAT (beta = 0.442, 95% CI 0.030-0.814; P
      = 0.036) and in plasma (beta = 0.300, 95% CI 0.056-0.545; P = 0.017). SAT-derived
      SFRP4 mRNA levels were independently associated with fasting insulin levels (beta
      = 0.382, 95% CI 0.008-0.756; P = 0.045). In addition, plasma SFRP4 levels were
      positively correlated with BMI (r = 0.259, P = 0.030), fasting insulin levels (r
      = 0.306, P = 0.010) and homeostasis model assessment of insulin resistance (HOMA
      IR) values (r = 0.331, P = 0.005). CONCLUSIONS: EAT-derived and circulating SFRP4
      expression levels were increased in patients with CAD. EAT SFRP4 mRNA levels and
      plasma SFRP4 concentrations were independently associated with the presence of
      CAD.

PMID- 29037198
TI  - Prolonged survival of patients with EGFR-mutated non-small cell lung cancer with
      solitary brain metastases treated with surgical resection of brain and lung
      lesions followed by EGFR TKIs.
AB  - BACKGROUND: The standard combination of initial and subsequent treatments of
      epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer
      (NSCLC) patients with solitary brain metastases (BM) remain unclear. Thus, the
      management options and the progression-free survival (PFS) and the overall
      survival (OS) of EGFR-mutated NSCLC patients with solitary BM were investigated
      in the study. METHODS: We retrospectively reviewed the clinical data from NSCLC
      patients who harbored EGFR mutations and who presented solitary BM at diagnosis
      in our institute between 2012 and 2014. PFS and OS were evaluated using Kaplan
      Meier methods and compared using log-rank tests. RESULTS: In total, 36 NSCLC
      patients with solitary BM who harbored EGFR mutations were enrolled in this
      study. The PFS and OS of these patients was 12.4 and 19.3 months, respectively.
      Sixteen patients underwent surgical resection of brain and lung lesions followed
      by EGFR-TKIs treatment, and the median OS was 28.0 months, which was
      significantly longer than 16.4 months of 14 patients received radiotherapy
      combined with or followed by EGFR-tyrosine kinase inhibitors (TKIs) and 15.8
      months of 6 patients received radiotherapy followed by chemotherapy. The median
      PFS also showed the same trend in each group (16.1, 10.4, and 9.8 months,
      respectively). CONCLUSIONS: The survival was extended in the patients receiving
      surgical resection of brain and lung lesions followed by EGFR-TKIs treatment, and
      surgery combined with EGFR-TKIs could be a recommended treatment for EGFR mutated
      NSCLC patients with solitary BM.

PMID- 29037199
TI  - Assessment of local pulse wave velocity distribution in mice using k-t BLAST PC
      CMR with semi-automatic area segmentation.
AB  - BACKGROUND: Local aortic pulse wave velocity (PWV) is a measure for vascular
      stiffness and has a predictive value for cardiovascular events. Ultra high field
      CMR scanners allow the quantification of local PWV in mice, however these systems
      are yet unable to monitor the distribution of local elasticities. METHODS: In the
      present study we provide a new accelerated method to quantify local aortic PWV in
      mice with phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) at
      17.6 T. Based on a k-t BLAST (Broad-use Linear Acquisition Speed-up Technique)
      undersampling scheme, total measurement time could be reduced by a factor of 6.
      The fast data acquisition enables to quantify the local PWV at several locations
      along the aortic blood vessel based on the evaluation of local temporal changes
      in blood flow and vessel cross sectional area. To speed up post processing and to
      eliminate operator bias, we introduce a new semi-automatic segmentation algorithm
      to quantify cross-sectional areas of the aortic vessel. The new methods were
      applied in 10 eight-month-old mice (4 C57BL/6J-mice and 6 ApoE (-/-)-mice) at 12
      adjacent locations along the abdominal aorta. RESULTS: Accelerated data
      acquisition and semi-automatic post-processing delivered reliable measures for
      the local PWV, similiar to those obtained with full data sampling and manual
      segmentation. No statistically significant differences of the mean values could
      be detected for the different measurement approaches. Mean PWV values were
      elevated for the ApoE (-/-)-group compared to the C57BL/6J-group (3.5 +/- 0.7 m/s
      vs. 2.2 +/- 0.4 m/s, p < 0.01). A more heterogeneous PWV-distribution in the ApoE
      (-/-)-animals could be observed compared to the C57BL/6J-mice, representing the
      local character of lesion development in atherosclerosis. CONCLUSION: In the
      present work, we showed that k-t BLAST PC-MRI enables the measurement of the
      local PWV distribution in the mouse aorta. The semi-automatic segmentation method
      based on PC-CMR data allowed rapid determination of local PWV. The findings of
      this study demonstrate the ability of the proposed methods to non-invasively
      quantify the spatial variations in local PWV along the aorta of ApoE (-/-)-mice
      as a relevant model of atherosclerosis.

PMID- 29037200
TI  - Spontaneous isolated dissection of the superior mesenteric artery and aneurysm
      formation resulting from segmental arterial mediolysis: a case report.
AB  - BACKGROUND: Spontaneous isolated dissection of the superior mesenteric artery
      (SMA) can lead to bowel ischemia, aneurysm rupture, or even death. Studies have
      suggested that mechanical or hemodynamic stress on the vascular wall of the SMA
      may be a contributor, but its pathogenesis is unclear. CASE PRESENTATION: A 57
      year-old Japanese man with a history of untreated hypertension and hyperuricemia
      was admitted to our hospital with the sudden onset of severe epigastric pain.
      Laboratory findings showed elevated white blood cell count and C-reactive
      protein, and contrast-enhanced computed tomography (CT) of the abdomen
      demonstrated arterial dissection with luminal stenosis and aneurysm formation at
      the distal portion of the SMA after the branching of the jejunal artery, and
      intravenous nicardipine was administered. The patient's epigastric pain resolved
      spontaneously but recurred on day 6 of his hospital stay. Contrast-enhanced
      abdominal CT revealed an enlarged aneurysm with wall thinning. Because of the
      risk of aneurysm rupture, the decision was made to perform aneurysmectomy and
      bowel resection on day 6. Histologic examinations revealed two separate
      dissecting lesions: one latent and the other resulting in aneurysm formation.
      Both lesions showed characteristics of segmental arterial mediolysis (SAM) with
      lack of arterial media, absence of internal and external elastic laminae and
      intimal proliferation. CONCLUSIONS: Histologic findings in the present case
      suggest that mechanical or hemodynamic stress on the vascular wall and SAM
      related vascular vulnerability may concomitantly contribute to the onset of
      isolated SMA dissection.

PMID- 29037201
TI  - Evaluation on the diagnostic and prognostic values of long non-coding RNA BLACAT1
      in common types of human cancer.
AB  - A growing number of evidence has indicated that long non-coding RNAs (lncRNA) may
      have many functions in the development and progression of cancer, and cloud serve
      as good diagnostic and prognostic biomarkers in cancers. However, these studies
      often revealed the changes of lncRNAs within a specific cancer type. Here, we
      focused on BLACAT1 and provided a comprehensive pan-cancer analysis to evaluate
      the diagnostic and prognostic values of BLACAT1. The expression data of BLACAT1
      were came from the quantitative real-time polymerase chain reaction (qRT-PCR) and
      The Cancer Genome Atlas (TCGA) database, respectively. Our results showed that
      the change of serum BLACAT1 expression was similar to those in matched tissues.
      The expression level of BLACAT1 both in serum and tissues in multiple cancer
      types were significantly upregulated compared to those of matched non-cancer
      participants. The serum BLACAT1 had a high diagnostic performance among these 12
      types of cancer. The relative AUC of serum BLACAT1 in cancer patients ranged from
      0.833 to 0.967 compared to that in healthy subjects. Surprisingly, Kaplan-Meier
      survival analysis revealed that the high expression level of BLACAT1 was
      significantly associated with poor overall survival only in uterine corpus
      endometrial carcinoma (p = 0.002, log-rank test). These findings demonstrated
      that BLACAT1 could act as a non-specific diagnostic biomarker for cancers and a
      potential biomarker for prognosis prediction of endometrial cancer.

PMID- 29037202
TI  - High prevalence of very-low Plasmodium falciparum and Plasmodium vivax
      parasitaemia carriers in the Peruvian Amazon: insights into local and
      occupational mobility-related transmission.
AB  - BACKGROUND: The incidence of malaria due both to Plasmodium falciparum and
      Plasmodium vivax in the Peruvian Amazon has risen in the past 5 years. This study
      tested the hypothesis that the maintenance and emergence of malaria in
      hypoendemic regions such as Amazonia is determined by submicroscopic and
      asymptomatic Plasmodium parasitaemia carriers. The present study aimed to
      precisely quantify the rate of very-low parasitaemia carriers in two sites of the
      Peruvian Amazon in relation to transmission patterns of P. vivax and P.
      falciparum in this area. METHODS: This study was carried out within the Amazonian
      ICEMR longitudinal cohort. Blood samples were collected for light microscopy
      diagnosis and packed red blood cell (PRBC) samples were analysed by qPCR. Plasma
      samples were tested for total IgG reactivity against recombinant PvMSP-10 and
      PfMSP-10 antigens by ELISA. Occupation and age 10 years and greater were
      considered surrogates of occupation-related mobility. Risk factors for P.
      falciparum and P. vivax infections detected by PRBC-qPCR were assessed by
      multilevel logistic regression models. RESULTS: Among 450 subjects, the
      prevalence of P. vivax by PRBC-PCR (25.1%) was sixfold higher than that
      determined by microscopy (3.6%). The prevalence of P. falciparum infection was
      4.9% by PRBC-PCR and 0.2% by microscopy. More than 40% of infections had
      parasitaemia under 5 parasites/MUL. Multivariate analysis for infections detected
      by PRBC-PCR showed that participants with recent settlement in the study area
      (AOR 2.1; 95% CI 1.03:4.2), age >= 30 years (AOR 3.3; 95% CI 1.6:6.9) and
      seropositivity to P. vivax (AOR 1.8; 95% CI 1.0:3.2) had significantly higher
      likelihood of P. vivax infection, while the odds of P. falciparum infection was
      higher for participants between 10 and 29 years (AOR 10.7; 95% CI 1.3:91.1) and
      with a previous P. falciparum infection (AOR 10.4; 95% CI 1.5:71.1). CONCLUSIONS:
      This study confirms the contrasting transmission patterns of P. vivax and P.
      falciparum in the Peruvian Amazon, with stable local transmission for P. vivax
      and the source of P. falciparum to the study villages dominated by very low
      parasitaemia carriers, age 10 years and older, who had travelled away from home
      for work and brought P. falciparum infection with them.

PMID- 29037203
TI  - The impact of an innovative web-based school nutrition intervention to increase
      fruits and vegetables and milk and alternatives in adolescents: a clustered
      randomized trial.
AB  - BACKGROUND: The increase in overweight and obesity in adolescents and its health
      related consequences highlight the need to develop strategies, which could help
      them adopt healthy eating habits. The objective of this study was to evaluate the
      impact of an innovative web-based school nutrition intervention (Team
      Nutriathlon) aimed at promoting the consumption of vegetables and fruit (V/F) and
      milk and alternatives (M/A) in high school students and to identify facilitators
      and/or barriers influencing its success. METHODS: Ten classes of first and second
      year secondary students (grades 7 and 8) from the Quebec City region were
      randomized into two groups (control n = 89 and intervention n = 193).
      Participants in the intervention (Team Nutriathlon) were to increase their
      consumption of V/F and M/A using an innovative web-based platform, developed for
      this study, over 6 weeks. The control group followed the regular school
      curriculum. The number of servings of V/F and M/A consumed by students per day
      was compared between the two groups before, during, immediately after and 10
      weeks after the intervention using a web-based platform. Main outcome measures
      included V/F and M/A servings and facilitators and/or barriers of program
      success. Repeated measures linear fixed effects models were used to assess the
      impact of Team Nutriathlon on V/F and M/A consumption. A P-value of <0.05 was
      considered significant. RESULTS: Students in the intervention reported a
      significant increase of 3 servings and 1.8 servings per day of V/F and M/A,
      respectively, compared to the control group (P < 0.05); however, this was only
      observed in the short-term. Some factors contributing to the success of Team
      Nutriathlon included the team aspect of the program, use of the technology and
      recording results outside of classroom hours. CONCLUSION: Team Nutriathlon
      represents an innovative web-based nutrition program which positively impacts V/F
      and M/A consumption among high school students. Using web-based or technological
      platforms may help youth adopt healthy eating habits that will have implications
      later in adulthood; however, further studies are needed to determine their long
      term effects. TRIAL REGISTRATION: NCT03117374 (retrospectively registered).

PMID- 29037204
TI  - Thoracodorsal artery perforator flap as an autologous alternative to acellular
      dermal matrix.
AB  - BACKGROUND: Thoracodorsal artery perforator (TDAP) flap is one of the relatively
      new techniques in breast reconstruction. This pedicled flap retains the benefits
      of perforator flaps as regards minimal donor site morbidity without the need for
      microvascular anastomosis. Its role in partial breast reconstruction has been
      well documented. However, there are few reports about the role of this flap in
      total breast reconstruction. METHODS: This study included 47 cases who presented
      to the breast unit of the National Cancer Institute of Cairo University from 2013
      to 2015. All patients underwent nipple-sparing mastectomy with immediate implant
      based reconstruction. The TDAP flap was used to complete the subpectoral pocket
      for the implants in a way similar to the acellular dermal matrix. RESULTS:
      Overall complication rate was 14.9%. Capsular contracture occurred in 6.4%.There
      were no donor site complications. The majority of patients were satisfied with
      their cosmetic results. Sixty-eight percent rated their result as "excellent" or
      "good." CONCLUSION: Thoracodorsal artery perforator flap can play a significant
      role in total breast reconstruction. In settings with limited resources, this
      flap can serve as an available autologous alternative to acellular dermal matrix.

PMID- 29037205
TI  - Vildagliptin ameliorates pulmonary fibrosis in lipopolysaccharide-induced lung
      injury by inhibiting endothelial-to-mesenchymal transition.
AB  - BACKGROUND: Pulmonary fibrosis is a late manifestation of acute respiratory
      distress syndrome (ARDS). Sepsis is a major cause of ARDS, and its pathogenesis
      includes endotoxin-induced vascular injury. Recently, endothelial-to-mesenchymal
      transition (EndMT) was shown to play an important role in pulmonary fibrosis. On
      the other hand, dipeptidyl peptidase (DPP)-4 was reported to improve vascular
      dysfunction in an experimental sepsis model, although whether DPP-4 affects EndMT
      and fibrosis initiation during lipopolysaccharide (LPS)-induced lung injury is
      unclear. The aim of this study was to investigate the anti-EndMT effects of the
      DPP-4 inhibitor vildagliptin in pulmonary fibrosis after systemic endotoxemic
      injury. METHODS: A septic lung injury model was established by intraperitoneal
      injection of lipopolysaccharide (LPS) in eight-week-old male mice (5 mg/kg for
      five consecutive days). The mice were then treated with vehicle or vildagliptin
      (intraperitoneally, 10 mg/kg, once daily for 14 consecutive days from 1 day
      before the first administration of LPS.). Flow cytometry, immunohistochemical
      staining, and quantitative polymerase chain reaction (qPCR) analysis was used to
      assess cell dynamics and EndMT function in lung samples from the mice. RESULTS:
      Lung tissue samples from treated mice revealed obvious inflammatory reactions and
      typical interstitial fibrosis 2 days and 28 days after LPS challenge.
      Quantitative flow cytometric analysis showed that the number of pulmonary
      vascular endothelial cells (PVECs) expressing alpha-smooth muscle actin (alpha
      SMA) or S100 calcium-binding protein A4 (S100A4) increased 28 days after LPS
      challenge. Similar increases in expression were also confirmed by qPCR of mRNA
      from isolated PVECs. EndMT cells had higher proliferative activity and migration
      activity than mesenchymal cells. All of these changes were alleviated by
      intraperitoneal injection of vildagliptin. Interestingly, vildagliptin and
      linagliptin significantly attenuated EndMT in the absence of immune cells or GLP
      1. CONCLUSIONS: Inhibiting DPP-4 signaling by vildagliptin could ameliorate
      pulmonary fibrosis by downregulating EndMT in systemic LPS-induced lung injury.

PMID- 29037206
TI  - Effects of continuous visual feedback during sitting balance training in chronic
      stroke survivors.
AB  - BACKGROUND: Postural control deficits are common in stroke survivors and often
      the rehabilitation programs include balance training based on visual feedback to
      improve the control of body position or of the voluntary shift of body weight in
      space. In the present work, a group of chronic stroke survivors, while sitting on
      a force plate, exercised the ability to control their Center of Pressure with a
      training based on continuous visual feedback. The goal of this study was to test
      if and to what extent chronic stroke survivors were able to learn the task and
      transfer the learned ability to a condition without visual feedback and to
      directions and displacement amplitudes different from those experienced during
      training. METHODS: Eleven chronic stroke survivors (5 Male - 6 Female, age: 59.72
      +/- 12.84 years) participated in this study. Subjects were seated on a stool
      positioned on top of a custom-built force platform. Their Center of Pressure
      positions were mapped to the coordinate of a cursor on a computer monitor. During
      training, the cursor position was always displayed and the subjects were to reach
      targets by shifting their Center of Pressure by moving their trunk. Pre and post
      training subjects were required to reach without visual feedback of the cursor
      the training targets as well as other targets positioned in different directions
      and displacement amplitudes. RESULTS: During training, most stroke survivors were
      able to perform the required task and to improve their performance in terms of
      duration, smoothness, and movement extent, although not in terms of movement
      direction. However, when we removed the visual feedback, most of them had no
      improvement with respect to their pre-training performance. CONCLUSIONS: This
      study suggests that postural training based exclusively on continuous visual
      feedback can provide limited benefits for stroke survivors, if administered
      alone. However, the positive gains observed during training justify the
      integration of this technology-based protocol in a well-structured and
      personalized physiotherapy training, where the combination of the two approaches
      may lead to functional recovery.

PMID- 29037207
TI  - TREM2 deficiency exacerbates tau pathology through dysregulated kinase signaling
      in a mouse model of tauopathy.
AB  - BACKGROUND: Genetic variants of the Triggering Receptor Expressed on Myeloid
      Cells-2 (TREM2) confer increased risk of developing late-onset Alzheimer's
      Disease (LOAD) and other neurodegenerative disorders. Recent studies provided
      insight into the multifaceted roles of TREM2 in regulating extracellular beta
      amyloid (Abeta) pathology, myeloid cell accumulation, and inflammation observed
      in AD, yet little is known regarding the role of TREM2 in regulating
      intracellular microtubule associated protein tau (MAPT; tau) pathology in
      neurodegenerative diseases and in AD, in particular. RESULTS: Here we report that
      TREM2 deficiency leads to accelerated and exacerbated hyperphosphorylation and
      aggregation of tau in a humanized mouse model of tauopathy. TREM2 deficiency also
      results, indirectly, in dramatic widespread dysregulation of neuronal stress
      kinase pathways. CONCLUSIONS: Our results suggest that deficiency of microglial
      TREM2 leads to heightened tau pathology coupled with widespread increases in
      activated neuronal stress kinases. These findings offer new insight into the
      complex, multiple roles of TREM2 in regulating Abeta and tau pathologies.

PMID- 29037208
TI  - Light/dark phase-dependent spontaneous activity is maintained in dopamine
      deficient mice.
AB  - Dopamine is important for motor control and involved in the regulation of
      circadian rhythm. We previously found that dopamine-deficient (DD) mice became
      hyperactive in a novel environment 72 h after the last injection of L-3,4
      dihydroxyphenylalanine (L-DOPA) when dopamine was almost completely depleted. DD
      mice did not initially exhibit hyperactivity in their home cages, but the animals
      exhibited hyperactivity several hours after the last L-DOPA injection. The
      regulation of motor activity in a novel environment and in home cages may be
      different. A previous study reported that DD mice became active again
      approximately 24 h after the last L-DOPA injection. One speculation was that
      light/dark phase-dependent spontaneous activity might be maintained despite
      dopamine deficiency. The present study investigated whether spontaneous home cage
      activity is maintained in DD mice 24-43 h and 72-91 h after the last L-DOPA
      injection. Spontaneous activity was almost completely suppressed during the light
      phase of the light/dark cycle in DD mice 24 and 72 h after the last L-DOPA
      injection. After the dark phase began, DD mice became active 24 and 72 h after
      the last L-DOPA injection. DD mice exhibited a similar amount of locomotor
      activity as wildtype mice 24 h after the last L-DOPA injection. Although DD mice
      presented a decrease in activity 72 h after the last L-DOPA injection, they
      maintained dark phase-stimulated locomotor activation. Despite low levels of
      dopamine in DD mice, they exhibited feeding behavior that was similar to wildtype
      mice. Although grooming and rearing behavior significantly decreased, DD mice
      retained their ability to perform these activities. Haloperidol treatment
      significantly suppressed all of these behaviors in wildtype mice but not in DD
      mice. These results indicate that DD mice maintain some aspects of light/dark
      phase-dependent spontaneous activity despite dopamine depletion, suggesting that
      compensatory dopamine-independent mechanisms might play a role in the DD mouse
      phenotype.

PMID- 29037209
TI  - Understanding the effects of socioeconomic status along the breast cancer
      continuum in Australian women: a systematic review of evidence.
AB  - BACKGROUND: Globally, the provision of equitable outcomes for women with breast
      cancer is a priority for governments. However, there is growing evidence that a
      socioeconomic status (SES) gradient exists in outcomes across the breast cancer
      continuum - namely incidence, diagnosis, treatment, survival and mortality. This
      systematic review describes this evidence and, because of the importance of place
      in defining SES, findings are limited to the Australian experience. METHODS: An
      on-line search of PubMed and the Web of Science identified 44 studies published
      since 1995 which examined the influence of SES along the continuum. The critique
      of studies included the study design, the types and scales of SES variable
      measured, and the results in terms of direction and significance of the
      relationships found. To aid in the interpretation of results, the findings were
      discussed in the context of a systems dynamic feedback diagram. RESULTS: We found
      67 findings which reported 107 relationships between SES within outcomes along
      the continuum. Results suggest no differences in the participation in screening
      by SES. Higher incidence was reported in women with higher SES whereas a negative
      association was reported between SES and diagnosis. Associations with treatment
      choice were specific to the treatment choice undertaken. Some evidence was found
      towards greater survival for women with higher SES, however, the evidence for a
      SES relationship with mortality was less conclusive. CONCLUSIONS: In a universal
      health system such as that in Australia, evidence of an SES gradient exists,
      however, the strength and direction of this relationship varies along the
      continuum. This is a complex relationship and the heterogeneity in study design,
      the SES indicator selected and its representative scale further complicates our
      understanding of its influence. More complex multilevel studies are needed to
      better understand these relationships, the interactions between predictors and to
      reduce biases introduced by methodological issues.

PMID- 29037212
TI  - Chromatin remodeling factor lymphoid-specific helicase inhibits ferroptosis
      through lipid metabolic genes in lung cancer progression.

PMID- 29037211
TI  - Pioglitazone and the secondary prevention of cardiovascular disease. A meta
      analysis of randomized-controlled trials.
AB  - BACKGROUND AND AIMS: Pioglitazone targets multiple pathogenic pathways involved
      in the development of cardiovascular diseases (CVD). The aim of this systematic
      review and meta-analysis is to assess the effects of pioglitazone treatment on
      the secondary prevention of CVD. METHODS: Randomized-controlled trials of
      pioglitazone in patients with CVD were identified through PubMed, Embase,
      Cochrane and CINAHL, in a search up to May 2016. Studies were included if
      pioglitazone was compared with any control (usual care, placebo or active
      comparator) and if patients were previously diagnosed with CVD. The outcomes of
      interest included major adverse cardiovascular events (MACE), myocardial
      infarction (MI), stroke, all-cause mortality and heart failure (HF). All outcomes
      were compared by pooled risk ratios (RR) with a 95% confidence interval (CI).
      Pooled estimates were calculated using a random-effects model. RESULTS: Ten
      studies reported the effects of pioglitazone on any of the outcomes of interest.
      Pioglitazone reduced recurrent MACE (RR 0.74, 95% 0.60-0.92; I2 = 35), MI (RR
      0.77, 95% CI 0.64-0.93; I2 = 0%), or stroke (RR 0.81, 95% CI 0.68-0.96; I2 = 0%).
      Pioglitazone did not reduce all-cause mortality (RR 0.94, 95% CI 0.81-1.08; I2 =
      0%), whereas pioglitazone treatment was associated with an increased risk of HF
      (RR 1.33, 95% CI 1.14-1.54). CONCLUSIONS: Pioglitazone lowers the risk of
      recurrent MACE, stroke, or MI in patients with clinical manifest vascular
      disease. Pioglitazone does not lower the risk for all-cause mortality, and
      increases the risk for the development of HF.

PMID- 29037210
TI  - A vicious circle between insulin resistance and inflammation in nonalcoholic
      fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of diseases,
      including simple steatosis, nonalcoholic steatohepatitis (NASH), liver cirrhosis
      and hepatocellular carcinoma. Lipotoxicity, insulin resistance (IR) and
      inflammation are involved in the disease process. Lipotoxicity promotes
      inflammation and IR, which in turn, increase adipocyte lipolysis and exacerbates
      lipotoxicity. Furthermore, IR and inflammation form a vicious circle, with each
      condition promoting the other and accelerating the development of NAFLD in the
      presence of lipotoxicity. As an integrator of inflammatory pathway networks,
      nuclear factor-kappa B (NF-kappaB) regulates expression of pro-inflammatory
      cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6),
      and anti-inflammatory cytokines, such as adiponectin in NAFLD. In this review,
      the relationships between lipotoxicity, IR and inflammation in NAFLD are
      discussed, with particular emphasis on the inflammatory pathways.

PMID- 29037213
TI  - Personalized treatment of women with early breast cancer: a risk-group specific
      cost-effectiveness analysis of adjuvant chemotherapy accounting for companion
      prognostic tests OncotypeDX and Adjuvant!Online.
AB  - BACKGROUND: Due to high survival rates and the relatively small benefit of
      adjuvant therapy, the application of personalized medicine (PM) through risk
      stratification is particularly beneficial in early breast cancer (BC) to avoid
      unnecessary harms from treatment. The new 21-gene assay (OncotypeDX, ODX) is a
      promising prognostic score for risk stratification that can be applied in
      conjunction with Adjuvant!Online (AO) to guide personalized chemotherapy
      decisions for early BC patients. Our goal was to evaluate risk-group specific
      cost effectiveness of adjuvant chemotherapy for women with early stage BC in
      Austria based on AO and ODX risk stratification. METHODS: A previously validated
      discrete event simulation model was applied to a hypothetical cohort of 50-year
      old women over a lifetime horizon. We simulated twelve risk groups derived from
      the joint application of ODX and AO and included respective additional costs. The
      primary outcomes of interest were life-years gained, quality-adjusted life-years
      (QALYs), costs and incremental cost-effectiveness (ICER). The robustness of
      results and decisions derived were tested in sensitivity analyses. A cross
      country comparison of results was performed. RESULTS: Chemotherapy is dominated
      (i.e., less effective and more costly) for patients with 1) low ODX risk
      independent of AO classification; and 2) low AO risk and intermediate ODX risk.
      For patients with an intermediate or high AO risk and an intermediate or high ODX
      risk, the ICER is below 15,000 EUR/QALY (potentially cost effective depending on
      the willingness-to-pay). Applying the AO risk classification alone would miss
      risk groups where chemotherapy is dominated and thus should not be considered.
      These results are sensitive to changes in the probabilities of distant recurrence
      but not to changes in the costs of chemotherapy or the ODX test. CONCLUSIONS:
      Based on our modeling study, chemotherapy is effective and cost effective for
      Austrian patients with an intermediate or high AO risk and an intermediate or
      high ODX risk. In other words, low ODX risk suggests chemotherapy should not be
      considered but low AO risk may benefit from chemotherapy if ODX risk is high. Our
      analysis suggests that risk-group specific cost-effectiveness analysis, which
      includes companion prognostic tests are essential in PM.

PMID- 29037214
TI  - Thyroid function and metabolic syndrome in the population-based LifeLines cohort
      study.
AB  - BACKGROUND: The metabolic syndrome (MetS) is a combination of unfavourable health
      factors which includes abdominal obesity, dyslipidaemia, elevated blood pressure
      and impaired fasting glucose. Earlier studies have reported a relationship
      between thyroid function and some MetS components or suggested that serum free
      thyroxine (FT4) or free triiodothyronine (FT3) levels within the normal range
      were independently associated with insulin resistance. We assessed how thyroid
      function relates to MetS prevalence in a large population-based study. METHODS:
      Data of 26,719 people of western European descent, aged 18-80 years from the
      Dutch LifeLines Cohort study, all with normal thyroid stimulating hormone (TSH),
      FT4 and FT3 levels (electrochemiluminescent immunoassay, Roche Modular E170
      Analyzer), were available. MetS was defined with the revised National Cholesterol
      Education Programs Adults Treatment Panel III (NCEP ATP III) criteria. We
      calculated prevalence of all MetS components according to TSH, FT4 and FT3
      quartiles. RESULTS: At similar TSH levels and age (mean 45 yrs), men had
      significantly higher levels of FT4, FT3, blood pressure (BP), heart rate, total
      and LDL-cholesterol, triglycerides (TG), and creatinine, but lower HDL
      cholesterol compared to women (all p < 0.001). In total, 11.8% of women and 20.7%
      of men had MetS. In men, lower FT4 levels were associated with higher prevalence
      of MetS and all MetS components. In women, lower FT4 quartile was only associated
      with a higher prevalence of elevated TG, waist circumference, and MetS. However,
      when corrected for confounding factors like age, BMI, current smoking and alcohol
      consumption, a significant relationship was found between FT3 and three MetS
      components in men, and all five components in women. Moreover, the highest
      quartiles of FT3 and the FT3FT4 ratio predicted a 49% and 67% higher prevalence
      of MetS in men, and a 62 and 80% higher prevalence in women. CONCLUSIONS: When
      corrected for possible confounding factors, higher plasma levels of FT3 are
      associated with several components of the MetS. Only in men, lower FT4 is related
      to MetS. In the highest FT3 and FT3FT4 quartiles, there is a 50-80% increased
      risk of having MetS compared to the lowest quartile. Further studies are needed
      to assess the possible causality of this relationship.

PMID- 29037216
TI  - Exploring the impact of the care sport connector in the Netherlands.
AB  - BACKGROUND: Regular physical activity (PA) is deemed to contribute to the primary
      and secondary prevention of several chronic diseases, like diabetes mellitus,
      cancer, cardiovascular diseases, and osteoporosis. In 2012, Care Sport Connectors
      (CSC), to whom a broker has been ascribed, were introduced in the Netherlands to
      stimulate PA and guide primary care patients towards local sport facilities. The
      aim of this study was to explore which structural embedding is the most promising
      for CSCs' work. METHODS: In three rounds of interviews, 13 CSCs were followed for
      2 years in their work. In these interviews, a network survey was used to identify
      organisations in the CSCs' network, whether they collaborated with these
      organisations, and the role of the organisations in the connection. Data from the
      network survey were analysed using the RE-AIM framework and disaggregated into
      how CSCs were structurally embedded (Type A: only PA sector; Type B: different
      sectors; Type C: partnership). A related samples Wilcoxon signed rank test was
      performed to study how the CSCs' network developed between 2014 and 2016.
      RESULTS: All CSCs established a connection between the primary care and the PA
      sector in which the average number of organisations with which CSCs collaborated
      increased significantly between 2014 (8.3) and 2016 (19.8) (p = 0.002). However,
      differences were identified in the way CSCs were structurally embedded and in the
      way they established the connection. Type A CSCs established the connection
      mostly around their own activities, supported PA organisations with their
      activities, and collaborated with primary care and welfare professionals around
      their own activities. Type B and Type C CSCs established the connection by
      organising, supporting, and implementing different kinds of activities targeting
      different kinds of audiences, and collaborated mostly with primary care
      professionals around the referral of professionals' patients. CONCLUSIONS: The
      results of this study suggest that adopting an integral approach (Type B and C)
      for the structural embedding of the CSC is more promising for reaching the
      desired outcomes. Whether CSCs really improve the target groups' PA level and
      health needs to be further studied. TRIAL REGISTRATION: Dutch Trial Register
      NTR4986 . Registered 14 December 2014.

PMID- 29037215
TI  - Melanoma brain metastases treated with stereotactic radiosurgery and concurrent
      pembrolizumab display marked regression; efficacy and safety of combined
      treatment.
AB  - BACKGROUND: Brain metastases are common in patients with metastatic melanoma.
      With increasing numbers of melanoma patients on anti-PD-1 therapy, we sought to
      evaluate the safety and initial response of brain metastases treated with
      concurrent pembrolizumab and radiation therapy. METHODS: From an institutional
      database, we retrospectively identified patients with melanoma brain metastases
      treated with radiation therapy (RT) who received concurrent pembrolizumab.
      Concurrent treatment was defined as RT during pembrolizumab administration period
      and up to 4 months after most recent pembrolizumab treatment. Response was
      categorized by change in maximum diameter on first scheduled follow-up MRI.
      Lesion and patient specific outcomes including response, lesion control, brain
      control and overall survival were recorded and descriptively compared to
      contemporary treatments with RT and concurrent ipilimumab or RT without
      immunotherapy. RESULTS: From January 2014 through December 2015, we identified 21
      patients who received concurrent radiation therapy and pembrolizumab for brain
      metastases or resection cavities that had at least one scheduled follow-up MRI.
      Eleven underwent stereotactic radiosurgery (SRS), 7 received hypofractionated
      radiation and 3 had whole brain treatment (WBRT). All treatments were well
      tolerated with no observed Grade 4 or 5 toxicities; Grade 3 edema and confusion
      occurred in 1 patient treated with WBRT after prior SRS. For metastases treated
      with SRS, at first scheduled follow-up MRI (median 57 days post SRS), 70% (16/23)
      exhibited complete (CR, n = 8) or partial response (PR, n = 8). The intracranial
      response rates (CR/PR) for patients treated with SRS and concurrent ipilimumab
      and SRS without concurrent immunotherapy was 32% and 22%, respectively.
      CONCLUSIONS: Concurrent pembrolizumab with brain RT appears safe in patients with
      metastatic melanoma, and SRS in particular is effective in markedly reducing the
      size of brain metastases at the time of first follow-up MRI. These results
      compare favorably to SRS in combination with ipilimumab and SRS without
      concurrent immunotherapy.

PMID- 29037218
TI  - Clinicopathologic features and treatment efficacy of Chinese patients with BRAF
      mutated metastatic colorectal cancer: a retrospective observational study.
AB  - BACKGROUND: The prognostic role of the V600E mutation of v-raf murine sarcoma
      viral oncogene homolog B1 (BRAF) in metastatic colorectal cancer (mCRC) is well
      established, but the therapeutic regimen targeting this disease is lacking. This
      study aimed to analyze the clinicopathologic features of and treatment efficacy
      of commonly used regimens on BRAF-mutated mCRCs. METHODS: We collected and
      reviewed the medical records of mCRC patients treated at Peking University Cancer
      Hospital & Institute (Beijing, China) between July 2011 and July 2016. Kirsten
      rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene
      homolog (NRAS), and BRAF mutational status was assayed using direct sequencing.
      The details of clinicopathologic characteristics of patients and their responses
      to FOLFOXIRI regimen or standard therapy were obtained by reviewing the medical
      records. The progression-free survival (PFS) and overall survival (OS) were
      assessed using Kaplan-Meier analysis and compared using the log-rank test.
      RESULTS: Of 1694 patients studied, 75 had BRAF exon 15 mutations. Of these 75
      patients, 71 had V600E mutation, 1 had D594G mutation, 2 had K601E mutation, and
      1 had a novel T599_V600insAGA alteration. No patients had KRAS or NRAS mutations.
      Of 63 patients with BRAF V600E-mutated mCRC and sufficient clinical data, 27
      (42.9%) had right-sided colon tumors, 19 (30.2%) had left-sided colon tumors, and
      17 (26.9%) had rectal tumors; 26 (41.3%) had peritoneal metastases, and 50
      (79.4%) had distant lymph node metastases. The patients with BRAF K601E- and
      T599_V600insAGA-mutated tumors had similar clinicopathologic features to those
      with BRAF V600E-mutated tumors. Patients with the BRAF V600E mutation benefited
      more from FOLFOXIRI regimen compared with patients who underwent standard therapy
      (overall response rate 83.3% vs. 14.0%; median PFS 6.4 months vs. 2.8 months, P =
      0.220; median OS 11.0 months vs. 6.9 months, P = 0.048). CONCLUSIONS: BRAF V600E
      mutations were commonly identified in right-sided tumors and showed a high
      incidence of peritoneal and distant lymph nodes metastases. This subtype of mCRC
      was characterized by short OS and unique patterns of metastasis. Compared with
      standard treatment regimens, the FOLFOXIRI regimen had acceptable and manageable
      toxicities and favorable efficacy on patients with BRAF-mutated mCRC.

PMID- 29037217
TI  - Subtype-specific differentiation of cardiac pacemaker cell clusters from human
      induced pluripotent stem cells.
AB  - BACKGROUND: Human induced pluripotent stem cells (hiPSC) harbor the potential to
      differentiate into diverse cardiac cell types. Previous experimental efforts were
      primarily directed at the generation of hiPSC-derived cells with ventricular
      cardiomyocyte characteristics. Aiming at a straightforward approach for pacemaker
      cell modeling and replacement, we sought to selectively differentiate cells with
      nodal-type properties. METHODS: hiPSC were differentiated into spontaneously
      beating clusters by co-culturing with visceral endoderm-like cells in a serum
      free medium. Subsequent culturing in a specified fetal bovine serum (FBS)
      enriched cell medium produced a pacemaker-type phenotype that was studied in
      detail using quantitative real-time polymerase chain reaction (qRT-PCR),
      immunocytochemistry, and patch-clamp electrophysiology. Further investigations
      comprised pharmacological stimulations and co-culturing with neonatal
      cardiomyocytes. RESULTS: hiPSC co-cultured in a serum-free medium with the
      visceral endoderm-like cell line END-2 produced spontaneously beating clusters
      after 10-12 days of culture. The pacemaker-specific genes HCN4, TBX3, and TBX18
      were abundantly expressed at this early developmental stage, while levels of
      sarcomeric gene products remained low. We observed that working-type
      cardiomyogenic differentiation can be suppressed by transfer of early clusters
      into a FBS-enriched cell medium immediately after beating onset. After 6 weeks
      under these conditions, sinoatrial node (SAN) hallmark genes remained at high
      levels, while working-type myocardial transcripts (NKX2.5, TBX5) were low.
      Clusters were characterized by regular activity and robust beating rates (70-90
      beats/min) and were triggered by spontaneous Ca2+ transients recapitulating
      calcium clock properties of genuine pacemaker cells. They were responsive to
      adrenergic/cholinergic stimulation and able to pace neonatal rat ventricular
      myocytes in co-culture experiments. Action potential (AP) measurements of cells
      individualized from clusters exhibited nodal-type (63.4%) and atrial-type (36.6%)
      AP morphologies, while ventricular AP configurations were not observed.
      CONCLUSION: We provide a novel culture media-based, transgene-free approach for
      targeted generation of hiPSC-derived pacemaker-type cells that grow in clusters
      and offer the potential for disease modeling, drug testing, and individualized
      cell-based replacement therapy of the SAN.

PMID- 29037219
TI  - Meta-analysis on the treatment of diabetic foot ulcers with autologous stem
      cells.
AB  - Over the last decade, many studies have indicated a therapeutic potential for
      treating diabetic lower extremity ulcers with autologous stem cells. The aim of
      the current study was to conduct a systematic review and meta-analysis of the
      treatment of diabetic foot ulcers (DFUs) with autologous stem cells. The search
      strategy included the Pubmed, EMBASE, Web of Science, and Cochrane's Library
      databases. The endpoint measured was the healing of DFUs.Six eligible randomized
      controlled trial (RCT) studies were screened from related published studies and
      reviewed for meta-analysis. The overall meta-analysis showed that stem cell
      administration was significantly favorable for healing diabetic ulcers (mean
      difference (MD) 0.52, 95% confidence interval (CI) 0.38-0.65; p < 0.00001).
      Subgroup analyses indicated that stem cells seemed to exert similar beneficial
      effects on patients with ulcer size >= 5 cm2 (MD 0.76, 95% CI 0.55-0.97; p <
      0.00001) and < 5 cm2 (MD 0.43, 95% CI 0.31-0.54; p < 0.00001). Furthermore, stem
      cells had similar effects on patients aged >= 70 years (MD 0.61, 95% CI 0.14
      1.08; p = 0.01) and < 70 years (MD 0.47, 95% CI 0.35-0.58; p < 0.00001). This
      systematic review and meta-analysis suggests a promising role for stem cells in
      DFU treatment. This review will pave the way to further study on the long-term
      effects of stem cell-based therapy and large-scale RCTs.

PMID- 29037220
TI  - circGFRA1 and GFRA1 act as ceRNAs in triple negative breast cancer by regulating
      miR-34a.
AB  - BACKGROUD: Accumulating evidences indicate that circular RNAs (circRNAs), a class
      of non-coding RNAs, play important roles in tumorigenesis. However, the function
      of circRNAs in triple negative breast cancer (TNBC) is largely unknown. METHODS:
      We performed circRNA microarrays to identify circRNAs that are aberrantly
      expressed in TNBC cell lines. Expression levels of a significantly upregulated
      circRNA, circGFRA1, was detected by quantitative real-time PCR (qRT-PCR) in TNBC
      cell lines and tissues. Kaplan-Meier survival analysis was used to explore the
      significance of circGFRA1 in clinical prognosis. Then, we examined the functions
      of circGFRA1 in TNBC by cell proliferation, apoptosis and mouse xenograft assay.
      In addition, luciferase assay was used to explore the miRNA sponge function of
      circGFRA1 in TNBC. RESULTS: Microarray analysis and qRT-PCR verified a circRNA
      termed circGFRA1 that was upregulated in TNBC. Kaplan-Meier survival analysis
      showed that upregulated circGFRA1 was correlated with poorer survival. Knockdown
      of circGFRA1 inhibited proliferation and promoted apoptosis in TNBC. Via
      luciferase reporter assays, circGFRA1 and GFRA1 was observed to directly bind to
      miR-34a. Subsequent experiments showed that circGFRA1 and GFRA1 regulated the
      expression of each other by sponging miR-34a. CONCLUSIONS: Taken together, we
      conclude that circGFRA1 may function as a competing endogenous RNA (ceRNA) to
      regulate GFRA1 expression through sponging miR-34a to exert regulatory functions
      in TNBC. circGFRA1 may be a diagnostic biomarker and potential target for TNBC
      therapy.

PMID- 29037221
TI  - High-flow oxygen via nasal cannulae in patients with acute hypoxemic respiratory
      failure: a systematic review and meta-analysis.
AB  - BACKGROUND: We performed a systematic review and meta-analysis to evaluate the
      efficacy and safety of high-flow oxygen via nasal cannulae (HFNC) compared to non
      invasive ventilation (NIV) and/or standard oxygen in patients with acute,
      hypoxemic respiratory failure. METHODS: We reviewed randomized controlled trials
      from CENTRAL, EMBASE, MEDLINE, Scopus and the International Clinical Trials
      Registry Platform (inception to February 2016), conference proceedings, and
      relevant article reference lists. Two reviewers independently screened and
      extracted trial-level data from trials investigating HFNC in patients with acute,
      hypoxemic respiratory failure. Internal validity was assessed in duplicate using
      the Cochrane Risk of Bias tool. The strength of evidence was assessed in
      duplicate using the Grading of Recommendations Assessment, Development and
      Evaluation framework. Our primary outcome was mortality. Secondary outcomes
      included dyspnea, PaO2:FiO2 ratio, PaCO2, and pH. Safety outcomes included
      respiratory arrest, intubation, delirium, and skin breakdown. RESULTS: From 2023
      screened citations, we identified seven trials (1771 patients) meeting inclusion
      criteria. All trials were at high risk of bias due to lack of blinding. There was
      no evidence for a mortality difference in patients receiving HFNC vs. NIV and/or
      standard oxygen (RR 1.01, 95% CI 0.69 to 1.48, I 2 = 63%, five trials, 1629
      patients). In subgroup analyses of HFNC compared to NIV or standard oxygen
      individually, mortality differences were not observed. Measures of patient
      tolerability were heterogeneous. The PaO2:FiO2 ratio at 6-12 h was significantly
      lower in patients receiving oxygen via HFNC compared to NIV or standard oxygen
      for hypoxemic respiratory failure (MD - 53.34, 95% CI - 71.95 to - 34.72, I 2 =
      61%, 1143 patients). There were no differences in pH, PaCO2, or rates of
      intubation or cardio-respiratory arrest. Delirium and skin breakdown were
      infrequently reported in included trials. CONCLUSIONS: In patients with acute
      hypoxemic respiratory failure HFNC was not associated with a difference in
      mortality compared to NIV or standard oxygen. Secondary outcomes including
      dyspnea, tolerance, and safety were not systematically reported. Residual
      heterogeneity and variable reporting of secondary outcomes limit the conclusions
      that can be made in this review. Prospective trials designed to evaluate the
      efficacy and safety of HFNC in patients with acute hypoxemic respiratory failure
      are required.

PMID- 29037223
TI  - Comparison of efficacy and complications of endoscopic and percutaneous biliary
      drainage in malignant obstructive jaundice: a systematic review and meta
      analysis.
AB  - BACKGROUND: Malignant obstructive jaundice is a common problem in the clinic.
      Currently, the generally applied treatment methods are percutaneous transhepatic
      biliary drainage (PTBD) and endoscopic biliary drainage (EBD). Nevertheless,
      there has not been a uniform conclusion published on either efficacy of the two
      types of drainage or the incidence rate of complications. Therefore, we conducted
      a systematic review and meta-analysis of studies comparing endoscopic versus
      percutaneous biliary drainage in malignant obstructive jaundice, to determine
      whether there is any difference between percutaneous and endoscopic biliary
      drainage, with respect to efficacy and incidence rate of overall complications.
      METHODS: The enrolled studies contain a total of three randomized controlled
      trials and eleven retrospective studies, which together encompass 2246 patients
      with PTBD and 8100 patients with EBD. RESULTS: Our analysis indicates that there
      is no difference between PTBD and EBD with regard to therapeutic success rate
      (%), overall complication (%), intraperitoneal bile leak, 30-day mortality,
      sepsis, or duodenal perforation (%). Cholangitis and pancreatitis after PTBD were
      lower than after EBD, with odds ratios (OR) of 0.48 (95% confidence interval
      (CI), 0.31 to 0.74) and 0.16 (95% CI, 0.05 to 0.52), respectively. Incidences of
      bleeding and tube dislocation for PTBD were higher than EBD, OR of 1.81 (95% CI,
      1.35 to 2.44) and 3.41 (95% CI, 1.10 to 10.60). CONCLUSIONS: This meta-analysis
      indicates certain advantages for both PTBD and EBD. In the clinical practice, it
      is advised to choose specifically either PTBD or EBD, based on location of
      obstruction, purpose of drainage (as a preoperative procedure or a palliative
      treatment) and level of experience in biliary drainage at individual treatment
      centers.

PMID- 29037222
TI  - The efficacy and stability of an information and communication technology-based
      centralized monitoring system of adherence to immunosuppressive medication in
      kidney transplant recipients: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Immunosuppression non-adherence in kidney transplant recipients
      (KTRs) not only increases the risk of medical intervention due to acute rejection
      and graft loss but burdens the socioeconomic system in the form of increased
      healthcare costs. An aggressive preemptive effort by healthcare professionals,
      geared to ensure adherence to immunosuppressants in KTRs, is significant and
      imperative. METHODS/DESIGN: This study was designed as a prospective, open-label,
      multicenter, randomized controlled study aimed at evaluating the efficacy and
      stability of an information and communication technology (ICT)-based centralized
      monitoring system in boosting medication adherence in KTRs. One hundred fourteen
      KTRs registered throughout the year 2017 to 2018 are randomized into either the
      ICT-based centralized home monitoring system or to ambulatory follow-up. The
      planned follow-up duration is 6 months. The ICT-based centralized home monitoring
      system described consists of a smart pill box equipped with personal
      identification system, a home monitoring system, an electronic Case Report Form
      (eCRF) system, and a comprehensive clinical trial management system (CTMS). It
      alerts both patients and medical staff with texts and pill box alarms if there is
      a dosage/dosing time error or a missed dose. Medication adherence and transplant
      outcomes for the follow-up period are compared between the two groups, while
      patient satisfaction as well as the stability and cost-effectiveness of the ICT
      based monitoring system are to be evaluated. DISCUSSION: This on-going study is
      expected to determine if consistent use of the ICT-based centralized monitoring
      system described could maximize mediation adherence and subsequently enhance
      transplant outcomes in KTRs. Further, it would lay the foundation for successful
      implementation of this ICT-based monitoring system for effective management of
      medication adherence in KTRs. TRIALS REGISTRATION: ClinicalTrials.gov,
      Identifier: NCT03136588 . Registered on 20 April 2017.

PMID- 29037224
TI  - Maternal and fetal blood lipid concentrations during pregnancy differ by maternal
      body mass index: findings from the ROLO study.
AB  - BACKGROUND: Pregnancy is a time of altered metabolic functioning and maternal
      blood lipid profiles change to accommodate the developing fetus. While these
      changes are physiologically necessary, blood lipids concentrations have been
      associated with adverse pregnancy outcomes such as gestational diabetes,
      pregnancy-induced hypertension and high birth weight. As blood lipids are not
      routinely measured during pregnancy, there is limited information on what is
      considered normal during pregnancy and in fetal blood. METHODS: Data from 327
      mother-child pairs from the ROLO longitudinal birth cohort study were analysed.
      Fasting total cholesterol and triglycerides were measured in early and late
      pregnancy and fetal cord blood. Intervals were calculated using the 2.5th, 50th
      and 97.5th centile. Data was stratified based on maternal body mass index (BMI)
      measured during early pregnancy. Differences in blood lipids between BMI
      categories were explored using ANOVA and infant outcomes of macrosomia and large
      for-gestational-age (LGA) were explored using independent student T-tests and
      binary logistic regression. RESULTS: All maternal blood lipid concentrations
      increased significantly from early to late pregnancy. In early pregnancy, women
      with a BMI < 25 kg/m2 had lower concentrations of total cholesterol compared to
      women with a BMI of 25-29.9 kg/m2 (P = 0.02). With triglycerides, women in the
      obese category (BMI > 30 kg/m2) had higher concentrations than both women in the
      normal-weight and overweight category in early and late pregnancy (P < 0.001 and
      P = 0.03, respectively). In late pregnancy, triglyceride concentrations remained
      elevated in women in the obese category compared to women in the normal-weight
      category (P = 0.01). Triglyceride concentrations were also elevated in late
      pregnancy in mothers that then gave birth to infants with macrosomia and LGA (P =
      0.01 and P = 0.03, respectively). CONCLUSION: Blood lipid concentrations increase
      during pregnancy and differ by maternal BMI. These intervals could help to inform
      the development of references for blood lipid concentrations during pregnancy.
      TRIAL REGISTRATION: ROLO Study - ISRCTN54392969 . Date of registration:
      22/04/2009.

PMID- 29037226
TI  - Xingnaojing for Moderate-to-severe Acute ischemic Stroke (XMAS): study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: Xingnaojing injection (XNJ) is widely used for the treatment of
      stroke in China. However, there is currently a lack of high-quality evidence of
      its efficacy for acute ischemic stroke. The main objective of this study is to
      determine whether the addition of XNJ to standard care improves the 3-month
      functional outcome in patients with acute ischemic stroke (AIS). METHODS/DESIGN:
      The XMAS study is a multicenter, prospective, randomized controlled, open-label
      trial with a blinded endpoints design. A total of 720 patients will be randomly
      allocated to either the intervention or the control group in a 1:1 ratio. The
      intervention group receives XNJ combined with standard care, and the control
      group receives standard care alone. XNJ will be administered intravenously every
      12 h for 10 days. The primary outcome is the proportion of patients who are
      independent at 3 months after stroke onset defined as a modified Rankin Scale
      score of 0 to 2. Secondary outcomes include early neurological deterioration at
      48 h, the change in National Institutes of Health Stroke Scale score, patient
      reported outcome, symptomatic intracranial hemorrhage at 10 days, the Barthel
      Index score, deaths from any cause and cardiovascular events at 3 months.
      DISCUSSION: The results of this trial will provide critical evidence for XNJ in
      the treatment of AIS as a complementary approach that can be initiated after
      reperfusion therapy or when the AIS is not eligible for thrombolytic treatment.
      TRIAL REGISTRATION: Clinical Trials.gov, ID: NCT02728180 . Registered on 28 March
      2016.

PMID- 29037225
TI  - YAP transcriptionally regulates COX-2 expression and GCCSysm-4 (G-4), a dual
      YAP/COX-2 inhibitor, overcomes drug resistance in colorectal cancer.
AB  - BACKGROUND: Chemotherapy resistance remains a major challenge in cancer
      treatment. COX-2 (cyclooxygenase 2) is involved in drug resistance and poor
      prognosis of many neoplastic diseases or cancers. However, investigations
      identifying new modulators of COX-2 pathway and searching for new chemicals
      targeting these valid resistant biomarkers are still greatly needed. METHODS:
      HCT15, HCT-116, HT-29, COLO205, FHC, IMCE, SW480 cell lines were used to detect
      the expression of YAP and COX-2. Site-directed mutagenesis, luciferase reporter
      analysis and ChIP assay were used to test whether YAP activated COX-2
      transcription through interaction with TEAD binding sites in the promoter of COX
      2. Cell line models exhibiting overexpression or knockdown of some genes were
      generated using transfection agents. Coimmunoprecipitation was used to detect
      protein mutual interaction. mRNA and protein levels were measured by qRT-PCR and
      western blot respectively. RESULTS: Here, we reported that both YAP and COX-2
      were overexpressed in colorectal cancer cells. YAP increased COX-2 expression at
      the level of transcription requiring intact TEAD binding sites in the COX-2
      promoter. YAP conferred drug resistance through COX-2 and its related effectors
      such as MCL, MDR, Survivin. GCCSysm-4 (G-4), a YAP and COX-2 inhibitor,
      effectively inhibited both YAP and COX-2 activation, induced apoptosis and
      decreased viability in Taxol-resistant cells. Inhibition of YAP and COX-2 acted
      synergistically and more efficiently reduced the resistance of CRC cells than
      either of them alone. CONCLUSIONS: Our data provide new mechanisms that YAP is a
      new upstream regulator of COX-2 pathway and plays an important role in conferring
      resistance in CRC cells. G-4, targeting YAP-COX-2, may be a novel valuable
      strategy to combat resistance in CRC.

PMID- 29037227
TI  - Molecular detection of Bartonella spp. in deer ked (Lipoptena cervi) in Poland.
AB  - BACKGROUND: The bacteria of the genus Bartonella are obligate parasites of
      vertebrates. Their distribution range covers almost the entire world from
      America, Europe, Asia to Africa and Australia. Some species of Bartonella are
      pathogenic for humans. Their main vectors are blood-sucking arthropods such as
      fleas, ticks and blood-feeding flies. One such dipteran able to transfer vector
      borne pathogens is the deer ked (Lipoptena cervi) of the family Hippoboscidae.
      This species acts as a transmitter of Bartonella spp. in cervid hosts in Europe.
      METHODS: In the present study, 217 specimens of deer ked (Lipoptena cervi) were
      collected from 26 red deer (Cervus elaphus) hunted in January 2014. A short
      fragment (333 bp) of the rpoB gene was used as a marker to identify Bartonella
      spp. in deer ked tissue by PCR test. A longer fragment (850 bp) of the rpoB gene
      was amplified from 21 of the positive samples, sequenced and used for
      phylogenetic analysis. RESULTS: The overall prevalence of Lipoptena cervi
      infection with Bartonella spp. was 75.12% (163/217); 86.67% (104/120) of females
      and 60.82% (59/97) of males collected from red deer hunted in the Strzalowo
      Forest District in Poland (53 degrees 45'57.03"N, 21 degrees 25'17.79"E) were
      infected. The nucleotide sequences from 14 isolates (Bartonella sp. 1) showed
      close similarity to Bartonella schoenbuchensis isolated from moose blood from
      Sweden (GenBank: KB915628) and human blood from France (GenBank: HG977196);
      Bartonella sp. 2 (5 isolates) and Bartonella sp. 3 (one isolate) were similar to
      Bartonella sp. from Japanese sika deer (GenBank: AB703149), and Bartonella sp. 4
      (one isolate) was almost identical to Bartonella sp. isolated from Japanese sika
      deer from Japan (GenBank: AB703146). CONCLUSIONS: To the best of our knowledge,
      this is the first report to confirm the presence of Bartonella spp. in deer keds
      (Lipoptena cervi) in Poland by molecular methods. Bartonella sp. 1 isolates were
      most closely related to B. schoenbuchensis isolated from moose from Sweden and
      human blood from France. The rest of our isolates (Bartonella spp. 2-4) were
      similar to Bartonella spp. isolated from Japanese sika deer from Japan.

PMID- 29037229
TI  - Situation and determinants of the infant and young child feeding (IYCF)
      indicators in Madagascar: analysis of the 2009 Demographic and Health Survey.
AB  - BACKGROUND: Studies evaluating child feeding in Madagascar are scarce despite its
      importance in child growth during the first two years of life. This study
      assessed the associations between the WHO infant and young child feeding (IYCF)
      indicators and stunting and identified determinants of inappropriate child
      feeding practices. METHODS: The most recent Demographic and Health Survey was
      used including a total of 1956 infants aged 0-23 months. Logistic regressions
      were performed for the association between IYCF indicators and stunting and for
      the determination of risk factors for inappropriate feeding practices. RESULTS:
      The rates of initiation of breastfeeding within one hour after birth (77.2%),
      continued breastfeeding at one year (99.6%) and timely introduction of solid,
      semi-solid or soft foods at 6-8 months (88.3%) were high. Exclusive breastfeeding
      under 6 months (48.8%), attaining minimum dietary diversity (22.2%) and
      consumption of iron-rich foods (19.6%) were relatively low. Higher length-for-age
      was associated with achieving minimum dietary diversity (p<0.01). The other
      indicators assessed (early initiation of breastfeeding, exclusive breastfeeding
      under 6 months, timely introduction of complementary foods and consumption of
      iron-rich foods) were not associated with stunting. Infants born to mothers who
      had first given birth at an age younger than 19 were more likely not to be
      breastfed within one hour after birth, not to be exclusively breastfed and not to
      have the recommended dietary diversity. Infants whose mothers had low media
      exposure were at increased risk of being inappropriately fed. Low household
      wealth also was associated with higher odds of not meeting the minimum dietary
      diversity. CONCLUSIONS: Despite almost total continued breastfeeding at one year
      and early initiation of breastfeeding by more than three-quarter of mothers,
      minimum dietary diversity scores were still low, confirming the need for more
      effective programs for improving child feeding practices in Madagascar. Improving
      dietary diversity in children aged 6-23 months may help reduce stunting. The
      identified risk factors for inappropriate feeding practices could be used in
      directing future nutrition sensitive interventions.

PMID- 29037230
TI  - The impact of multiple interventions to reduce household exposure to second-hand
      tobacco smoke among women: a cluster randomized controlled trial in Kalutara
      district, Sri Lanka.
AB  - BACKGROUND: Second-hand smoke (SHS) in households remains a serious public health
      problem in Sri Lanka, partly due to a lack of voluntary prohibitions of tobacco
      smoking inside houses. Women are especially at risk of being exposed. Effective
      community based interventions to reduce the SHS in households targeting women is
      scarce. The objective of this study was to examine the impact of a multi
      component intervention on household SHS exposure among Sri Lankan women. METHODS:
      Thirty clusters of 25 women (aged 18-65) from 750 households were randomized into
      the intervention and control groups. Women in the intervention group were exposed
      to activities which focused on improving knowledge on the health effects of SHS,
      attitudes towards SHS exposure, right to a smoke-free living and women
      empowerment against smoking. The duration of the intervention was six months. The
      comparison group received no intervention. The primary outcome of interest was
      self-reported SHS exposure in the household within 7 days prior to data
      collection. The secondary outcomes were exposure in the past 30 days, knowledge
      of the health risks of exposure, attitudes towards exposure, right to smoke-free
      living, women empowerment against smoking, and smoking inside the homes. RESULTS:
      Final assessment was in 329 (89.6%) in the intervention group and 309 (85.8%) in
      the comparison group. Following the intervention, significantly lower proportion
      of women in the intervention group as compared to the control group reported SHS
      exposure in their households within 7-days (9.2% vs. 15.3%, p = 0.02) and 30-days
      (13.6% vs. 21.6%, p = 0.008) prior to the post survey. As compared to the control
      group, significantly higher median scores were observed in the intervention group
      on the knowledge of the health risks of exposure to SHS (p < 0.001), attitudes on
      exposure to SHS (p = 0.004), right to smoke free living (p = 0.001) and women
      empowerment (p < 0.001). CONCLUSION: Multi-component intervention activities were
      effective in reducing household exposure to SHS among women. TRIAL REGISTRATION:
      Sri Lanka Clinical Trials Registry SLCTR/2014/033.

PMID- 29037231
TI  - Optimal parameters for determining the LH surge in natural cycle frozen-thawed
      embryo transfers.
AB  - BACKGROUND: There is no consensus on the exact parameters that define the LH
      surge for natural cycle frozen-thawed embryo transfers (NC-FET). Accurately
      determining the LH surge would affect the timing, and subsequently the success
      rates, of embryo transfer. Therefore, the aim of this study was to delineate the
      optimal levels and relationship for luteinizing hormone (LH) and estradiol in an
      effort to optimally identify the LH surge in NC-FET. METHODS: It is a
      retrospective study that was performed in an academic medical center. Patients
      who underwent blastocyst NC-FET who either had preimplantation genetic screening
      (PGS) or were <35 years old but did not undergo PGS (non-PGS) were included in
      separate analyses. They were divided into two groups: Group A included patients
      whose LH surge was defined as the first attainment of LH >= 17 IU/L during the
      follicular phase with a >=30% drop in estradiol levels the following day; group B
      encompassed patients whose LH level continued to rise and the surge was defined
      as the highest serum LH level occurring a day after LH >= 17 IU/L despite a >=
      30% drop in estradiol levels. The main outcomes measures were implantation and
      live birth rates. RESULTS: Four hundred-seven non-PGS and 284 PGS NC-FET were
      included. Among non-PGS cycles, group A was associated with significantly higher
      implantation rates (48.7% vs. 38.1%) and live birth rates (52.9% vs. 40.1%)
      compared to group B. In contrast, group A and B had comparable live birth rates
      among PGS cycles. CONCLUSIONS: Among non-PGS cycles, measuring LH and estradiol
      levels the day after an LH >= 17 IU/L and defining the surge as the first day of
      LH >= 17 IU/L in the context of a >= 30% drop in estradiol the following day was
      associated with better NC-FET outcomes than defining the surge as the day
      representing the highest serum LH level despite a >=30% drop in estradiol levels.

PMID- 29037228
TI  - Neuroepigenetic mechanisms in disease.
AB  - Epigenetics allows for the inheritance of information in cellular lineages during
      differentiation, independent of changes to the underlying genetic sequence. This
      raises the question of whether epigenetic mechanisms also function in post
      mitotic neurons. During the long life of the neuron, fluctuations in gene
      expression allow the cell to pass through stages of differentiation, modulate
      synaptic activity in response to environmental cues, and fortify the cell through
      age-related neuroprotective pathways. Emerging evidence suggests that epigenetic
      mechanisms such as DNA methylation and histone modification permit these dynamic
      changes in gene expression throughout the life of a neuron. Accordingly, recent
      studies have revealed the vital importance of epigenetic players in the central
      nervous system and during neurodegeneration. Here, we provide a review of several
      of these recent findings, highlighting novel functions for epigenetics in the
      fields of Rett syndrome, Fragile X syndrome, and Alzheimer's disease research.
      Together, these discoveries underscore the vital importance of epigenetics in
      human neurological disorders.

PMID- 29037234
TI  - Women's attitudes, experiences and compliance concerning the use of Mindfetalness
      a method for systematic observation of fetal movements in late pregnancy.
AB  - BACKGROUND: Maternal perception of decreased fetal movements and low awareness of
      fetal movements are associated with a negative birth outcome. Mindfetalness is a
      method developed for women to facilitate systematic observations of the
      intensity, character and frequency of fetal movements in late pregnancy. We
      sought to explore women's attitudes, experiences and compliance in using
      Mindfetalness. METHODS: We enrolled 104 pregnant women treated at three maternity
      clinics in Stockholm, Sweden, from February to July of 2016. We educated 104
      women in gestational week 28-32 by providing information about fetal movements
      and how to practice Mindfetalness. Each was instructed to perform the assessment
      daily for 15 min. At each subsequent follow-up, the midwife collected information
      regarding their perceptions of Mindfetalness, and their compliance. Content
      analyses, descriptive and analytic statistics were used in the analysis of data.
      RESULTS: Of the women, 93 (89%) were positive towards Mindfetalness and
      compliance was high 78 (75%). Subjective responses could be binned into one of
      five categories: Decreased worry, relaxing, creating a relationship, more
      knowledge about the unborn baby and awareness of the unborn baby. Eleven (11%)
      women had negative perceptions of Mindfetalness, citing time, and the lack of
      need for a method to observe fetal movements as the most common reasons.
      CONCLUSION: Women in late pregnancy are generally positive about Mindfetalness
      and their compliance with daily use is high. The technique helped them to be more
      aware of, and create a relationship with, their unborn baby. Mindfetalness can be
      a useful tool in antenatal care. However, further study is necessary in order to
      determine whether the technique is able to reduce the incidence of negative birth
      outcome.

PMID- 29037233
TI  - Cancer incidence in Germany attributable to human papillomavirus in 2013.
AB  - BACKGROUND: It is estimated that a total of 120,000 new cancer cases in men and
      in women in more developed countries could be avoided if exposure to HPV was
      prevented. We used the nationwide pool of German population-based cancer registry
      data to estimate the burden of HPV-attributable cancer in this population for the
      year 2013. METHODS: Incident cases of cervical cancer, squamous cell carcinoma of
      the anus, oropharynx (OP), as well as of the vulva, vagina and penis were
      classified as potentially HPV-associated and identified from the nationwide
      cancer registry data-pool. We calculated the incidence and proportions of cancer
      with potentially HPV-associated morphologies. Estimation of the HPV-attributable
      incidence was based on prevalence-estimates of viral DNA in tumor cells in the
      respective sites, as provided from the international literature. RESULTS: From
      the overall 15,936 incident cases of anogenital and OP cancers in 2013, 6239
      female and 1358 male cancer cases were estimated to be attributable to HPV. The
      majority of HPV-attributable cases were contributed by cervical cancer (70.9% of
      female cancers) and oropharyngeal cancer (46.9% of male cancers). CONCLUSIONS:
      Even if most HPV-attributable cases were contributed by cervical cancer,
      anogenital cancer at sites other than the cervix, and oropharyngeal cancer
      substantially contribute to the burden of HPV-associated cancer. Our nationwide
      cancer registry data-analyses provide the baseline for long-term population-based
      monitoring of vaccination-effects on cancer incidence in Germany.

PMID- 29037232
TI  - A systematic investigation of the maximum tolerated dose of cytotoxic
      chemotherapy with and without supportive care in mice.
AB  - BACKGROUND: Cytotoxic chemotherapeutics form the cornerstone of systemic
      treatment of many cancers. Patients are dosed at maximum tolerated dose (MTD),
      which is carefully determined in phase I studies. In contrast, in murine studies,
      dosages are often based on customary practice or small pilot studies, which often
      are not well documented. Consequently, research groups need to replicate
      experiments, resulting in an excess use of animals and highly variable dosages
      across the literature. In addition, while patients often receive supportive
      treatments in order to allow dose escalation, mice do not. These issues could
      affect experimental results and hence clinical translation. METHODS: To address
      this, we determined the single-dose MTD in BALB/c and C57BL/6 mice for a range of
      chemotherapeutics covering the canonical classes, with clinical score and weight
      as endpoints. RESULTS: We found that there was some variation in MTDs between
      strains and the tolerability of repeated cycles of chemotherapy at MTD was drug
      dependent. We also demonstrate that dexamethasone reduces chemotherapy-induced
      weight loss in mice. CONCLUSION: These data form a resource for future studies
      using chemotherapy in mice, increasing comparability between studies, reducing
      the number of mice needed for dose optimisation experiments and potentially
      improving translation to the clinic.

PMID- 29037235
TI  - A push for public health: the effect of e-bikes on physical activity levels.
AB  - BACKGROUND: Cycling is considered to have a positive effect on public health
      through increased physical activity. In Norway, the e-bike is seen as a way of
      getting more people to cycle. However, the motorized assistance of an e-bike
      potentially eliminates any physical activity associated with its use. It is
      possible that the assumed health effect of increased cycling is "erased" through
      a reduction in other physical activities (a substitution effect). In this paper
      we study the public health effects of e-bikes using a combined cross-sectional
      and quasi-experimental design. First, we explore the existence of potentially
      hedonistic values in relation to interest in acquiring an e-bike and, second, we
      conduct an intervention study of physical activity pre- and post-purchase.
      METHODS: A sample of 340 people responded to a questionnaire before buying an e
      bike and follow-up 4 weeks later, when 45 had bought one. A further 28 (mainly
      physically inactive) were recruited through a Norwegian NGO. For a comparison
      group, 1995 people were recruited through the Falck National Register of Bicycle
      Owners. All respondents were asked about the intensity of their cycling,
      (kilometres cycled in the previous week), walking and physical activity in
      addition to cycling as means of transport (days and hours). RESULTS: A structural
      equation model showed that hedonistic life values, and general physical activity,
      were predictive of interest in buying an e-bike. However people who already
      cycled a lot showed less interest. The trial showed that increased cycling -
      whether as a mean of transport or exercise -was related to higher levels of total
      physical activity in both groups compared to a comparison group (one-way ANOVA).
      CONCLUSIONS: Our findings indicate that in the Norwegian cycle population there
      is no substantial substitution effect of physical activity with the introduction
      of an e-bike. The appeal of the e-bike is strongest among those with little
      existing interest in, or levels of, physical activity. The net effect of the e
      bike therefore seems positive from a public health perspective.

PMID- 29037236
TI  - A single-arm phase II study of nab-paclitaxel for patients with chemorefractory
      non-small cell lung cancer.
AB  - BACKGROUND: We aimed to evaluate the efficacy and safety of nab-paclitaxel in
      patients with refractory advanced non-small cell lung cancer who failed previous
      chemotherapy. METHODS: Patients were required to have an Eastern Cooperative
      Oncology Group performance status of 0-2 and adequate organ function. Patients
      received nab-paclitaxel, 100 mg/m2 i.v. on days 1, 8, and 15 every 4 weeks. The
      primary endpoint was the overall response rate. Secondary endpoints were the
      progression-free survival time, overall survival, and the toxicity profile.
      RESULTS: From July 2013 to July 2015, a total of 31 patients were enrolled.
      Fourteen patients received nab-paclitaxel as a second-line and 17 received it as
      an over third-line therapy. Each patient received a median of 5 treatment cycles
      (range, 1-11). The overall response rate was 19.3% (95% confidence interval, 9.1
      36.2%) (complete response (n = 0), partial response (n = 6), stable disease (n =
      17), and progressive disease (n = 8)). The median progression-free survival time
      was 4.5 months (95% confidence interval 3.5-6.3 months), median overall survival
      time was 15.7 months, and 1-year survival rate was 54.8%. Most common grade 3 or
      4 non-hematological toxicities were elevated aspartate transaminase level (3.2%)
      and sensory neuropathy (9.6%). Neutropenia was the most common grade 3 or 4
      adverse events (38.6%), and febrile neutropenia developed in 12.9% patients. No
      treatment-related deaths were observed in this study. CONCLUSION: Primary
      endpoint was met. Single agent nab-paclitaxel showed significant clinical
      efficacy and manageable toxicities for patients with chemorefractory advanced non
      small cell lung cancer even if late line setting. TRIAL REGISTRATION:
      UMIN000011696 . The date of registration was July 11th, 2013.

PMID- 29037237
TI  - The role of national registries in improving patient safety for hip and knee
      replacements.
AB  - BACKGROUND: The serious adverse events associated with metal on metal hip
      replacements have highlighted the importance of improving methods for monitoring
      surgical implants. The new European Union (EU) device regulation will enforce
      post-marketing surveillance based on registries among other surveillance tools.
      Europe has a common regulatory environment, a common market for medical devices,
      and extensive experience with joint replacement registries. In this context, we
      elaborate how joint replacement registries, while building on existing structure
      and data, can better ensure safety and balance risks and benefits. MAIN TEXT:
      Actions to improve registry-based implant surveillance include: enriching
      baseline and diversifying outcomes data collection; improving methodology to
      limit bias; speeding-up failure detection by active real-time monitoring;
      implementing risk-benefit analysis; coordinating collaboration between
      registries; and translating knowledge gained from the data into clinical decision
      making and public health policy. CONCLUSIONS: The changes proposed here will
      improve patient safety, enforce the application of the new legal EU requirements,
      augment evidence, improve clinical decision-making, facilitate value-based health
      care delivery, and provide up-to-date guidance for public health.

PMID- 29037239
TI  - Serum uric acid and non-alcoholic fatty liver disease in non-obesity Chinese
      adults.
AB  - BACKGROUND: Previous studies found elevated serum uric acid (SUA) was associated
      with the development or progression of non-alcoholic fatty liver disease (NAFLD)
      in general population; in this study we aim to investigate the association of SUA
      and the severity of NAFLD based on grade of fatty liver on ultrasonography in non
      obese subjects. METHODS: Data were obtained from subjects via routine physical
      examinations in the Public Health Center of our hospital between 2011 and 2014.
      The data included completed anthropometry and blood biochemical indicators and
      the results of abdominal ultrasound. The diagnosis of NAFLD was according to the
      clinical diagnosis of the Guidelines for the diagnosis and treatment of
      nonalcoholic fatty liver disease in 2008. RESULTS: In total, 95,924 subjects were
      analyzed in this study. The prevalence rate of lean-NAFLD was 8.16%, among which
      7.58% had mild steatosis, and 0.58% had moderate and severe steatosis. The
      prevalence of fatty liver was increased progressively with SUA. Among which the
      prevalence of mild fatty liver from Q1 to Q4 were 10.33%, 18.39%, 23.11% and
      25.93%; the prevalence of moderate and severe fatty liver from Q1 to Q4 were
      1.06%, 2.82%, 5.05% and 7.27%. Lean-subjects with hyperuricemia had an OR of
      1.718 (95% CI 1.622-1.820) to have NAFLD, after adjusted for other metabolic
      disorders. The area under curve (AUC) for detecting mild fatty liver based on SUA
      was 0.70; and the AUC for detecting moderate and severe fatty liver based on SUA
      was 0.78. CONCLUSIONS: Our data showed positive associations between elevated SUA
      levels and lean-NAFLD risk in the inland Chinese adults, independent of other
      metabolic factors. Our study also suggests that SUA could be considered as a
      simple and non-invasive method to follow up patients with lean-NAFLD.

PMID- 29037238
TI  - Developing dimensions for a multicomponent multidisciplinary approach to obesity
      management: a qualitative study.
AB  - BACKGROUND: There have been consistent recommendations for multicomponent and
      multidisciplinary approaches for obesity management. However, there is no clear
      agreement on the components, disciplines or processes to be considered within
      such an approach. In this study, we explored multicomponent and multidisciplinary
      approaches through an examination of knowledge, skills, beliefs, and
      recommendations of stakeholders involved in obesity management. These
      stakeholders included researchers, practitioners, educators, and patients.
      METHODS: We used qualitative action research methods, including convergent
      interviewing and observation, to assist the process of inquiry. RESULTS: The
      consensus was that a multicomponent and multidisciplinary approach should be
      based on four central meta-components (patient, practitioner, process, and
      environmental factors), and specific components of these factors were identified.
      Psychologists, dieticians, exercise physiologists and general practitioners were
      nominated as key practitioners to be included. CONCLUSIONS: A complex condition
      like obesity requires that multiple components be addressed, and that both
      patients and multiple disciplines are involved in developing solutions.
      Implementing cycles of continuous improvement to deal with complexity, instead of
      trying to control for it, offers an effective way to deal with complex, changing
      multisystem problems like obesity.

PMID- 29037240
TI  - KH176 under development for rare mitochondrial disease: a first in man randomized
      controlled clinical trial in healthy male volunteers.
AB  - BACKGROUND: Mitochondrial disorders are a clinically, biochemically and
      genetically heterogeneous group of multi-system diseases, with an unmet medical
      need for treatment. KH176 is an orally bio-available small molecule under
      development for the treatment of mitochondrial(-related) diseases. The compound
      is a member of a new class of drugs, acting as a potent intracellular redox
      modulating agent essential for the control of oxidative and redox pathologies.
      The aim of this randomized, placebo controlled, double-blinded phase 1 study was
      to test safety, tolerability and pharmacokinetics of single and multiple doses of
      KH176 in healthy male volunteers. Putative effects on redox related biomarkers
      were explored. RESULTS: KH176 was well tolerated up to and including a single
      dose of 800 mg and multiple doses of 400 mg b.i.d. for 7 Days. However, when the
      QT interval was corrected for heart rate, administration of single doses of 800
      and 2000 mg and at a multiple dose of 400 mg KH176 had marked effects. Post-hoc
      analysis of the ECGs showed clear changes in cardiac electrophysiology at single
      doses of 800 and 2000 mg and multiple doses of 400 mg b.i.d.. At lower doses,
      detailed ECG analysis showed no changes in electrophysiology compared to placebo.
      Exposure-response modelling of the cardiac intervals revealed an exposure range
      of KH176 without effects on cardiac conduction and provided a threshold of 1000
      ng/mL above which changes in intervals could occur. After single- and multiple
      dose administration, the pharmacokinetics of KH176 was more than dose
      proportional. KH176 accumulated to a small extent and food only slightly affected
      the pharmacokinetics of KH176, which was considered clinically irrelevant. Renal
      excretion of unchanged KH176 and its metabolite represents a minor pathway in the
      elimination of KH176. As expected in healthy volunteers no effects on redox
      biomarkers were observed. CONCLUSION: The study deemed that KH176 is well
      tolerated up to single doses of 800 mg and multiple doses of 400 mg b.i.d. and
      has a pharmacokinetic profile supportive for a twice daily dosing. Only at high
      doses, KH176 causes clinically relevant changes in cardiac electrophysiology,
      including prolonged QTc interval and changes in T wave morphology. A Phase 2
      clinical trial (100 mg b.i.d., orally) has been conducted recently of which the
      final results are expected Q1 2018. TRIAL REGISTRATION: NCT02544217 . Registered.
      ISRCTN43372293 . Retrospectively registered.

PMID- 29037241
TI  - The potassium channel KCa3.1 constitutes a pharmacological target for
      astrogliosis associated with ischemia stroke.
AB  - BACKGROUND: Reactive astrogliosis is one of the significantly pathological
      features in ischemic stroke accompanied with changes in gene expression,
      morphology, and proliferation. KCa3.1 was involved in TGF-beta-induced
      astrogliosis in vitro and also contributed to astrogliosis-mediated
      neuroinflammation in neurodegeneration disease. METHODS: Wild type mice and
      KCa3.1-/- mice were subjected to permanent middle cerebral artery occlusion
      (pMCAO) to evaluate the infarct areas by 2,3,5-triphenyltetrazolium hydrochloride
      staining and neurological deficit. KCa3.1 channels expression and cell
      localization in the brain of pMCAO mice model were measured by immunoblotting and
      immunostaining. Glia activation and neuron loss was measured by immunostaining.
      DiBAC4 (3) and Fluo-4AM were used to measure membrane potential and cytosolic
      Ca2+ level in oxygen-glucose deprivation induced reactive astrocytes in vitro.
      RESULTS: Immunohistochemistry on pMCAO mice infarcts showed strong upregulation
      of KCa3.1 immunoreactivity in reactive astrogliosis. KCa3.1-/- mice exhibited
      significantly smaller infarct areas on pMCAO and improved neurological deficit.
      Both activated gliosis and neuronal loss were attenuated in KCa3.1-/- pMCAO mice.
      In the primary cultured astrocytes, the expressions of KCa3.1 and TRPV4 were
      increased associated with upregulation of astrogliosis marker GFAP induced by
      oxygen-glucose deprivation. The activation of KCa3.1 hyperpolarized membrane
      potential and, by promoting the driving force for calcium, induced calcium entry
      through TRPV4, a cation channel of the transient receptor potential family.
      Double-labeled staining showed that KCa3.1 and TRPV4 channels co-localized in
      astrocytes. Blockade of KCa3.1 or TRPV4 inhibited the phenotype switch of
      reactive astrogliosis. CONCLUSIONS: Our data suggested that KCa3.1 inhibition
      might represent a promising therapeutic strategy for ischemia stroke.

PMID- 29037242
TI  - Malaria risk factors and care-seeking behaviour within the private sector among
      high-risk populations in Vietnam: a qualitative study.
AB  - BACKGROUND: Vietnam has successfully reduced malaria incidence by more than 90%
      over the past 10 years, and is now preparing for malaria elimination. However,
      the remaining malaria burden resides in individuals that are hardest to reach, in
      highly remote areas, where many malaria cases are treated through the informal
      private sector and are not reported to public health systems. This qualitative
      study aimed to contextualize and characterize the role of private providers, care
      seeking behaviour of individuals at high risk of malaria, as well as risk factors
      that should be addressed through malaria elimination programmes in Vietnam.
      METHODS: Semi-structured qualitative interviews were conducted with 11 key
      informants in Hanoi, 30 providers, 9 potential patients, and 11 individuals at
      risk of malaria in Binh Phuoc and Kon Tum provinces. Audio recorded interviews
      were transcribed and uploaded to Atlas TITM, themes were identified, from which
      programmatic implications and recommendations were synthesized. RESULTS:
      Qualitative interviews revealed that efforts for malaria elimination in Vietnam
      should concentrate on reaching highest-risk populations in remote areas as well
      their care providers, in particular private pharmacies, private clinics, and
      grocery stores. Among these private providers, diagnosis is currently based on
      symptoms, leaving unconfirmed cases that are not reported to public health
      surveillance systems. Among at-risk individuals, knowledge of malaria was
      limited, and individuals reported not taking full courses of treatment, a
      practice that threatens selection for drug resistance. Access to insecticide
      treated hammock nets, a potentially important preventive measure for settings
      with outdoor biting Anopheles vectors, was also limited. CONCLUSIONS: Malaria
      elimination efforts in Vietnam can be accelerated by targeting improved
      treatment, diagnosis, and reporting practices to private pharmacies, private
      clinics, and grocery stores. Programmes should also seek to increase awareness
      and understanding of malaria among at-risk populations, in particular the
      importance of using preventive measures and adhering to complete courses of anti
      malarial medicines.

PMID- 29037243
TI  - Gardening in the desert: a spatial optimization approach to locating gardens in
      rapidly expanding urban environments.
AB  - BACKGROUND: Food access is a global issue, and for this reason, a wealth of
      studies are dedicated to understanding the location of food deserts and the
      benefits of urban gardens. However, few studies have linked these two strands of
      research together to analyze whether urban gardening activity may be a step
      forward in addressing issues of access for food desert residents. METHODS: The
      Phoenix, Arizona metropolitan area is used as a case to demonstrate the utility
      of spatial optimization models for siting urban gardens near food deserts and on
      vacant land. The locations of urban gardens are derived from a list obtained from
      the Maricopa County Cooperative Extension office at the University of Arizona
      which were geo located and aggregated to Census tracts. Census tracts were then
      assigned to one of three categories: tracts that contain a garden, tracts that
      are immediately adjacent to a tract with a garden, and all other non-garden/non
      adjacent census tracts. Analysis of variance is first used to ascertain whether
      there are statistical differences in the demographic, socio-economic, and land
      use profiles of these three categories of tracts. A maximal covering spatial
      optimization model is then used to identify potential locations for future
      gardening activities. A constraint of these models is that gardens be located on
      vacant land, which is a growing problem in rapidly urbanizing environments
      worldwide. RESULTS: The spatial analysis of garden locations reveals that they
      are centrally located in tracts with good food access. Thus, the current
      distribution of gardens does not provide an alternative food source to occupants
      of food deserts. The maximal covering spatial optimization model reveals that
      gardens could be sited in alternative locations to better serve food desert
      residents. In fact, 53 gardens may be located to cover 96.4% of all food deserts.
      This is an improvement over the current distribution of gardens where 68 active
      garden sites provide coverage to a scant 8.4% of food desert residents.
      CONCLUSION: People in rapidly urbanizing environments around the globe suffer
      from poor food access. Rapid rates of urbanization also present an unused vacant
      land problem in cities around the globe. This paper highlights how spatial
      optimization models can be used to improve healthy food access for food desert
      residents, which is a critical first step in ameliorating the health problems
      associated with lack of healthy food access including heart disease and obesity.

PMID- 29037244
TI  - Prediction of microbe-disease association from the integration of neighbor and
      graph with collaborative recommendation model.
AB  - BACKGROUND: Accumulating clinical researches have shown that specific microbes
      with abnormal levels are closely associated with the development of various human
      diseases. Knowledge of microbe-disease associations can provide valuable insights
      for complex disease mechanism understanding as well as the prevention, diagnosis
      and treatment of various diseases. However, little effort has been made to
      predict microbial candidates for human complex diseases on a large scale.
      METHODS: In this work, we developed a new computational model for predicting
      microbe-disease associations by combining two single recommendation methods.
      Based on the assumption that functionally similar microbes tend to get involved
      in the mechanism of similar disease, we adopted neighbor-based collaborative
      filtering and a graph-based scoring method to compute association possibility of
      microbe-disease pairs. The promising prediction performance could be attributed
      to the use of hybrid approach based on two single recommendation methods as well
      as the introduction of Gaussian kernel-based similarity and symptom-based disease
      similarity. RESULTS: To evaluate the performance of the proposed model, we
      implemented leave-one-out and fivefold cross validations on the HMDAD database,
      which is recently built as the first database collecting experimentally-confirmed
      microbe-disease associations. As a result, NGRHMDA achieved reliable results with
      AUCs of 0.9023 +/- 0.0031 and 0.9111 in the validation frameworks of fivefold CV
      and LOOCV. In addition, 78.2% microbe samples and 66.7% disease samples are found
      to be consistent with the basic assumption of our work that microbes tend to get
      involved in the similar disease clusters, and vice versa. CONCLUSIONS: Compared
      with other methods, the prediction results yielded by NGRHMDA demonstrate its
      effective prediction performance for microbe-disease associations. It is
      anticipated that NGRHMDA can be used as a useful tool to search the most
      potential microbial candidates for various diseases, and therefore boosts the
      medical knowledge and drug development. The codes and dataset of our work can be
      downloaded from https://github.com/yahuang1991/NGRHMDA .

PMID- 29037245
TI  - Reduced antiretroviral drug efficacy and concentration in HIV-infected microglia
      contributes to viral persistence in brain.
AB  - BACKGROUND: In patients with HIV/AIDS receiving antiretroviral therapy (ART), HIV
      1 persistence in brain tissue is a vital and unanswered question. HIV-1 infects
      and replicates in resident microglia and trafficking macrophages within the brain
      although the impact of individual ART drugs on viral infection within these brain
      myeloid cells is unknown. Herein, the effects of contemporary ART drugs were
      investigated using in vitro and in vivo models of HIV-1 brain infection. RESULTS:
      The EC50 values for specific ART drugs in HIV-infected human microglia were
      significantly higher compared to bone marrow-derived macrophages and peripheral
      blood mononuclear cells. Intracellular ART drug concentrations in microglia were
      significantly lower than in human lymphocytes. In vivo brain concentrations of
      ART drugs in mice were 10 to 100-fold less in brain tissues compared with plasma
      and liver levels. In brain tissues from untreated HIV-infected BLT mice, HIV
      encoded RNA, DNA and p24 were present in human leukocytes while ART eradicated
      viral RNA and DNA in both brain and plasma. Interruption of ART resulted in
      detectable viral RNA and DNA and increased human CD68 expression in brains of HIV
      infected BLT mice. In aviremic HIV/AIDS patients receiving effective ART, brain
      tissues that were collected within hours of last ART dosing showed HIV-encoded
      RNA and DNA with associated neuroinflammatory responses. CONCLUSIONS: ART drugs
      show variable concentrations and efficacies in brain myeloid cells and tissues in
      drug-specific manner. Despite low drug concentrations in brain, experimental ART
      suppressed HIV-1 infection in brain although HIV/AIDS patients receiving
      effective ART had detectable HIV-1 in brain. These findings suggest that viral
      suppression in brain is feasible but new approaches to enhancing ART efficacy and
      concentrations in brain are required for sustained HIV-1 eradication from brain.

PMID- 29037247
TI  - The effect of a weight gain prevention intervention on moderate-vigorous physical
      activity among black women: the Shape Program.
AB  - BACKGROUND: Rates of physical inactivity are high among Black women living in the
      United States with overweight or obesity, especially those living in the rural
      South. This study was conducted to determine if an efficacious weight gain
      prevention intervention increased moderate-vigorous physical activity (MVPA).
      METHODS: The Shape Program, a weight gain prevention intervention implemented in
      community health centers in rural North Carolina, was designed for
      socioeconomically disadvantaged Black women with overweight or obesity. MVPA was
      measured using accelerometers, and summarized into 1- and 10-min bouts. We
      employed analyses of covariance (ANCOVA) to assess the relationship between
      changes in MVPA over 12 months, calculated as a change score, and intervention
      assignment (intervention versus usual care). RESULTS: Participants completing
      both baseline and 12-month accelerometer assessments (n = 121) had a mean age of
      36.1 (SD = 5.43) years and a mean body mass index of 30.24 kg/m2 (SD = 2.60). At
      baseline, 38% met the physical activity recommendation (150 min of MVPA/week)
      when assessed using 10-min bouts, and 76% met the recommendation when assessed
      using 1-min bouts. There were no significant differences in change in MVPA
      participation among participants randomized to the intervention from baseline to
      12-months using 1-min bouts (adjusted intervention mean [95% CI]: 20.50 [-109.09
      to 150.10] vs. adjusted usual care mean [95% CI]: -80.04 [-209.21 to 49.13], P =
      .29), or 10-min bouts (adjusted intervention mean [95% CI]: 7.39 [-83.57 to
      98.35] vs. adjusted usual care mean [95% CI]: -17.26 [-107.93 to 73.40], P =
      .70). CONCLUSIONS: Although prior research determined that the Shape intervention
      promoted weight gain prevention, MVPA did not increase significantly among
      intervention participants from baseline to 12 months. The classification of bouts
      had a marked effect on the prevalence estimates of those meeting physical
      activity recommendations. More research is needed to understand how to promote
      increased MVPA in weight gain prevention interventions. TRIAL REGISTRATION: This
      study is registered at www.clinicaltrials.gov database (No. NCT00938535.
      Retrospectively Registered 7/10/2009).

PMID- 29037246
TI  - Effectors of Th1 and Th17 cells act on astrocytes and augment their
      neuroinflammatory properties.
AB  - BACKGROUND: Autoreactive Th1 and Th17 cells are believed to mediate the pathology
      of multiple sclerosis in the central nervous system (CNS). Their interaction with
      microglia and astrocytes in the CNS is crucial for the regulation of the
      neuroinflammation. Previously, we have shown that only Th1 but not Th17 effectors
      activate microglia. However, it is not clear which cells are targets of Th17
      effectors in the CNS. METHODS: To understand the effects driven by Th17 cells in
      the CNS, we induced experimental autoimmune encephalomyelitis in wild-type mice
      and CD4+ T cell-specific integrin alpha4-deficient mice where trafficking of Th1
      cells into the CNS was affected. We compared microglial and astrocyte response in
      the brain and spinal cord of these mice. We further treated astrocytes with
      supernatants from highly pure Th1 and Th17 cultures and assessed the messenger
      RNA expression of neurotrophic factors, cytokines and chemokines, using real-time
      PCR. Data obtained was analyzed using the Kruskal-Wallis test. RESULTS: We
      observed in alpha4-deficient mice weak microglial activation but comparable
      astrogliosis to that of wild-type mice in the regions of the brain populated with
      Th17 infiltrates, suggesting that Th17 cells target astrocytes and not microglia.
      In vitro, in response to supernatants from Th1 and Th17 cultures, astrocytes
      showed altered expression of neurotrophic factors, pro-inflammatory cytokines and
      chemokines. Furthermore, increased expression of chemokines in Th1- and Th17
      treated astrocytes enhanced recruitment of microglia and transendothelial
      migration of Th17 cells in vitro. CONCLUSION: Our results demonstrate the
      delicate interaction between T cell subsets and glial cells and how they
      communicate to mediate their effects. Effectors of Th1 act on both microglia and
      astrocytes whereas Th17 effectors preferentially target astrocytes to promote
      neuroinflammation.

PMID- 29037248
TI  - Quantifying the importance of inhaler attributes corresponding to items in the
      patient satisfaction and preference questionnaire in patients using Combivent
      Respimat.
AB  - BACKGROUND: Physicians consider ease of use, satisfaction, and preferences when
      prescribing an inhaler device. These factors may impact appropriate usage and
      compliance. METHODS: The objectives were to quantify the relative importance of
      inhaler attributes in patients currently using Combivent Respimat by eliciting
      preferences for performance and convenience attributes assessed by items in the
      Patient Satisfaction and Preference Questionnaire (PASAPQ). Using a pharmacy
      database, 19,964 adults in the United States who filled >=2 Combivent Respimat
      prescriptions were identified. Of those, 8150 patients were randomly selected to
      receive invitation letters. The online cross-sectional survey included the PASAPQ
      and best-worst scaling (BWS) questions. The PASAPQ measures satisfaction with
      medication attributes across two domains: performance and convenience. BWS
      questions asked participants to select the most and least important device
      attributes. A descriptive statistics analysis of the PASAPQ and a random
      parameters logit model of BWS responses were conducted. RESULTS: The survey was
      completed by 503 participants. Most were female (57.3%), white (88.5%), and 51-70
      years old (67.6%). Approximately 47% reported a chronic obstructive pulmonary
      disease diagnosis, 21.9% asthma, 8.2% other lung disease, and 23.1% more than one
      lung disease. PASAPQ scores indicated that the majority were satisfied or very
      satisfied; up to 20% reported being dissatisfied with Combivent Respimat. The
      three most important inhaler attributes were Feeling that your medicine gets into
      your lungs, Inhaler works reliably, and Inhaler makes inhaling your medicine
      easy. The most important attributes corresponded to six of seven items in the
      PASAPQ performance domain. CONCLUSIONS: Most participants reported satisfaction
      with Combivent Respimat. Performance attributes were more important than
      convenience attributes.

PMID- 29037249
TI  - A novel self-micro-emulsifying delivery system (SMEDS) formulation significantly
      improves the fasting absorption of EPA and DHA from a single dose of an omega-3
      ethyl ester concentrate.
AB  - BACKGROUND: Absorption of EPA and DHA from Omega-3-acid ethyl ester (EE)
      concentrate supplements occurs most efficiently when taken in context of a fatty
      meal; adequate fat intake is required to release bile salts that emulsify and
      pancreatic enzymes that digest omega-3-containing lipids in the intestine.
      Current guidelines recommend reduction in fat intake and therefore there is a
      need to optimize the absorption of Omega-3 in those consuming low-fat or no-fat
      meals. To this end, BASF has developed an Absorption Acceleration Technology, a
      novel self-micro-emulsifying delivery system (SMEDS) formulation of highly
      concentrated Omega-3-acid EE which enables rapid emulsification and microdroplet
      formation upon entering the aqueous environment of the gut therefore enhances the
      absorption. METHODS: Two separate single dose, crossover studies were conducted
      to determine the relative bioavailability of omega-3-acid EE concentrate, either
      as a novel SMEDS formulation (PRF-021) or as control, in healthy fasted male and
      female adults at two dose levels (Study 1 "low dose": 630 mg EPA + DHA in PRF-021
      vs. 840 mg EPA + DHA in control; Study 2 "high dose": 1680 mg EPA + DHA in PRF
      021 vs. 3360 mg EPA + DHA in control). Blood samples were collected immediately
      before supplementation and at defined time intervals for 48 h. Plasma
      concentration of total EPA and DHA were determined for pharmacokinetic analysis,
      area under the curve (AUC) and maximum observed concentration (Cmax) was
      determined. RESULTS: Total EPA plus DHA absorption from SMEDS formulation PRF-021
      were 6.4 and 11.5 times higher compared to control in low- and high-dose studies
      respectively, determined as the ratio of baseline corrected, dose normalized AUC0
      24h of PRF-021 over that of control. EPA and DHA individually showed differing
      levels of enhancement: the AUC0-24h ratio for EPA was 23.8 and 25.7 in low and
      high dose studies, respectively, and the AUC0-24h ratio for DHA was 3.6 and 5.6
      in low and high dose studies, respectively. Cmax was also increased for both EPA
      and DHA 2.7- to 9.2-fold. CONCLUSION: PRF-021 is a novel SMEDS formulation of
      Omega-3-acid EE demonstrating a marked improvement in absorption of a single dose
      of EPA and DHA EE under fasted conditions. This allows adequate absorption of
      Omega-3 from the supplement without the requirement of a high-fat meal.

PMID- 29037250
TI  - The immune system in cancer metastasis: friend or foe?
AB  - Metastatic disease is the leading cause of death among cancer patients and
      involves a complex and inefficient process. Every step of the metastatic process
      can be rate limiting and is influenced by non-malignant host cells interacting
      with the tumor cell. Over a century ago, experiments first indicated a link
      between the immune system and metastasis. This phenomenon, called concomitant
      immunity, indicates that the primary tumor induces an immune response, which may
      not be sufficient to destroy the primary tumor, but prevents the growth of a
      secondary tumor or metastases. Since that time, many different immune cells have
      been shown to play a role in both inhibiting and promoting metastatic disease.
      Here we review classic and new observations, describing the links between the
      immune system and metastasis that inform the development of cancer therapies.

PMID- 29037252
TI  - Experiences of midwives on pharmacological and non-pharmacological labour pain
      management in Ghana.
AB  - BACKGROUND: Due to the debilitating effects of severe labour pains, labour pain
      management continues to be an important subject that requires much attention.
      Thus, this study sought to gain a detailed insight into the experiences of
      midwives on pharmacological and non-pharmacological labour pain management
      strategies in a resource limited clinical context. METHODS: A descriptive
      exploratory qualitative design was adopted for this study which allowed in-depth
      follow-up of the midwives' comments resulting in a full understanding of emerging
      findings. Face-to-face individual interviews were conducted, transcribed and data
      were analysed using content analysis procedures. Verbatim quotes were used to
      support the findings. RESULTS: Midwives employed different pain control measures
      including pharmacological and non-pharmacological methods such as psychological
      care, sacral massage and deep breathing exercises. Doctors prescribed analgesics
      most of the time while in some cases, the midwives independently administered the
      drugs. They assisted women who had epidural anaesthesia given by anaesthetists.
      The midwives did not administer adequate analgesics because of fear of side
      effects of analgesics. Although the midwives exhibited knowledge on drugs used
      for labour pain management, they did not regularly administer analgesics and non
      pharmacological care provided were inadequate due to increased workload. Some of
      the midwives showed empathy towards women and supported the women. Most of the
      midwives perceived labour pain as normal and encouraged women to bear pain.
      CONCLUSION: Midwives require regular education on labour pain management and they
      should pay attention to women in labour individually and administer the care that
      meets their need.

PMID- 29037254
TI  - Correction to: Anti-inflammatory and immune regulatory effects of acupuncture
      after craniotomy: study protocol for a parallel-group randomized controlled
      trial.

PMID- 29037251
TI  - Cytochrome c oxidase subunit 1 gene as a DNA barcode for discriminating
      Trypanosoma cruzi DTUs and closely related species.
AB  - BACKGROUND: The DNA barcoding system using the cytochrome c oxidase subunit 1
      mitochondrial gene (cox1 or COI) is highly efficient for discriminating
      vertebrate and invertebrate species. In the present study, we examined the
      suitability of cox1 as a marker for Trypanosoma cruzi identification from other
      closely related species. Additionally, we combined the sequences of cox1 and the
      nuclear gene glucose-6-phosphate isomerase (GPI) to evaluate the occurrence of
      mitochondrial introgression and the presence of hybrid genotypes. METHODS: Sixty
      two isolates of Trypanosoma spp. obtained from five of the six Brazilian biomes
      (Amazon Forest, Atlantic Forest, Caatinga, Cerrado and Pantanal) were sequenced
      for cox1 and GPI gene fragments. Phylogenetic trees were reconstructed using
      neighbor-joining, maximum likelihood, parsimony and Bayesian inference methods.
      Molecular species delimitation was evaluated through pairwise intraspecific and
      interspecific distances, Automatic Barcode Gap Discovery, single-rate Poisson
      Tree Processes and multi-rate Poisson Tree Processes. RESULTS: Both cox1 and GPI
      genes recognized and differentiated T. cruzi, Trypanosoma cruzi marinkellei,
      Trypanosoma dionisii and Trypanosoma rangeli. Cox1 discriminated Tcbat, TcI,
      TcII, TcIII and TcIV. Additionally, TcV and TcVI were identified as a single
      group. Cox1 also demonstrated diversity in the discrete typing units (DTUs) TcI,
      TcII and TcIII and in T. c. marinkellei and T. rangeli. Cox1 and GPI demonstrated
      TcI and TcII as the most genetically distant branches, and the position of the
      other T. cruzi DTUs differed according to the molecular marker. The tree
      reconstructed with concatenated cox1 and GPI sequences confirmed the separation
      of the subgenus Trypanosoma (Schizotrypanum) sp. and the T. cruzi DTUs TcI, TcII,
      TcIII and TcIV. The evaluation of single nucleotide polymorphisms (SNPs) was
      informative for DTU differentiation using both genes. In the cox1 analysis, one
      SNP differentiated heterozygous hybrids from TcIV sequences. In the GPI analysis
      one SNP discriminated Tcbat from TcI, while another SNP distinguished TcI from
      TcIII. CONCLUSIONS: DNA barcoding using the cox1 gene is a reliable tool to
      distinguish T. cruzi from T. c. marinkellei, T. dionisii and T. rangeli and
      identify the main T. cruzi genotypes.

PMID- 29037253
TI  - ASXL gain-of-function truncation mutants: defective and dysregulated forms of a
      natural ribosomal frameshifting product?
AB  - BACKGROUND: Programmed ribosomal frameshifting (PRF) is a gene expression
      mechanism which enables the translation of two N-terminally coincident, C
      terminally distinct protein products from a single mRNA. Many viruses utilize PRF
      to control or regulate gene expression, but very few phylogenetically conserved
      examples are known in vertebrate genes. Additional sex combs-like (ASXL) genes 1
      and 2 encode important epigenetic and transcriptional regulatory proteins that
      control the expression of homeotic genes during key developmental stages. Here we
      describe an ~150-codon overlapping ORF (termed TF) in ASXL1 and ASXL2 that, with
      few exceptions, is conserved throughout vertebrates. RESULTS: Conservation of the
      TF ORF, strong suppression of synonymous site variation in the overlap region,
      and the completely conserved presence of an EH[N/S]Y motif (a known binding site
      for Host Cell Factor-1, HCF-1, an epigenetic regulatory factor), all indicate
      that TF is a protein-coding sequence. A highly conserved UCC_UUU_CGU sequence
      (identical to the known site of +1 ribosomal frameshifting for influenza virus PA
      X expression) occurs at the 5' end of the region of enhanced synonymous site
      conservation in ASXL1. Similarly, a highly conserved RG_GUC_UCU sequence
      (identical to a known site of -2 ribosomal frameshifting for arterivirus nsp2TF
      expression) occurs at the 5' end of the region of enhanced synonymous site
      conservation in ASXL2. CONCLUSIONS: Due to a lack of appropriate splice forms, or
      initiation sites, the most plausible mechanism for translation of the ASXL1 and 2
      TF regions is ribosomal frameshifting, resulting in a transframe fusion of the N
      terminal half of ASXL1 or 2 to the TF product, termed ASXL-TF. Truncation or
      frameshift mutants of ASXL are linked to myeloid malignancies and genetic
      diseases, such as Bohring-Opitz syndrome, likely at least in part as a result of
      gain-of-function or dominant-negative effects. Our hypothesis now indicates that
      these disease-associated mutant forms represent overexpressed defective versions
      of ASXL-TF. REVIEWERS: This article was reviewed by Laurence Hurst and Eugene
      Koonin.

PMID- 29037255
TI  - Objective measurement and clinical significance of IDO1 protein in hormone
      receptor-positive breast cancer.
AB  - BACKGROUND: Immunostimulatory therapies targeting immune-suppressive pathways
      produce durable responses in advanced solid tumors. Indoleamine 2,3-dioxygenase
      (IDO) is the rate-limiting oxidoreductase that catalyzes the degradation of
      tryptophan to kynurenine. IDO induces immune tolerance by downregulating CD8+ and
      effector CD4+ T cell responses. IDO1, the most active isoform, is expressed in
      diverse tumor types and can be targeted using small molecule inhibitors. We used
      an objective, in situ assay to measure IDO1 in a collection of hormone receptor
      positive breast cancers (HR+ BC). METHODS: IDO1 protein was measured using
      quantitative immunofluorescence in 362 stage I-III HR+ BC represented in tissue
      microarrays. IDO1 levels were determined in the tumor and stroma, and stratified
      using median cut-point. Associations between IDO1, clinico-pathological features
      and CD3+, CD8+, CD20+ and FOXP3 tumor-infiltrating lymphocytes were examined
      using chi2 and Mann-Whitney tests. Survival was studied using Kaplan-Meier
      estimator and a proportional hazards model. All tests were two-sided. RESULTS:
      IDO1 protein was observed in 76.2% of HR+ BC. There was no association between
      IDO1 and major clinico-pathological characteristics. Increased IDO1 correlated
      with decreased CD20+ infiltration (P = 0.0004) but not with CD3+, CD8+ or FOXP3
      levels. Elevated IDO1 expression was associated with worse 20-year overall
      survival (log-rank P = 0.02, HR = 1.39, 95% C.I.: 1.05-1.82). IDO1 scores were
      independently associated with outcome in multivariable analysis. CONCLUSIONS:
      IDO1 protein is expressed in the majority of HR+ BC and is an independent
      negative prognostic marker. Additionally, IDO1 expression is negatively
      associated with tumor B-cell infiltration. Measurement of IDO1 has the potential
      to identify a population that might derive benefit from IDO1 blockade.

PMID- 29037256
TI  - Effects of timing on intracoronary autologous bone marrow-derived cell
      transplantation in acute myocardial infarction: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Several cell-based therapies for adjunctive treatment of acute
      myocardial infarction have been investigated in multiple clinical trials, but the
      timing of transplantation remains controversial. We conducted a meta-analysis of
      randomized controlled trials to investigate the effects of timing on bone marrow
      derived cell (BMC) therapy in acute myocardial infarction (AMI). METHODS: A
      systematic literature search of PubMed, MEDLINE, and Cochrane Evidence-Based
      Medicine databases from January 2000 to June 2017 was performed on randomized
      controlled trials with at least a 3-month follow-up for patients with AMI
      undergoing emergency percutaneous coronary intervention (PCI) and receiving
      intracoronary BMC transfer thereafter. The defined end points were left
      ventricular (LV) ejection fraction, LV end-diastolic and end-systolic index. The
      data were analyzed to evaluate the effects of timing on BMC therapy. RESULTS:
      Thirty-four RCTs comprising a total of 2,307 patients were included; the results
      show that, compared to the control group, AMI patients who received BMC
      transplantation showed significantly improved cardiac function. BMC
      transplantation 3-7 days after PCI (+3.32%; 95% CI, 1.91 to 4.74; P < 0.00001)
      resulted in a significant increase of left ventricular ejection fraction (LVEF).
      As for the inhibitory effect on ventricular remodeling, BMC transplantation 3-7
      days after PCI reduced LV end-diastolic indexes (-4.48; 95% CI, -7.98 to -0.98; P
      = 0.01) and LV end-systolic indexes (-6.73; 95% CI, -11.27 to -2.19; P = 0.004).
      However, in the groups who received BMC transplantation either within 24 hours or
      later than 7 days there was no significant effect on treatment outcome. In
      subgroup analysis, the group with LVEF <= 50% underwent a significant decrease in
      LV end-diastolic index after BMC transplantation (WMD = -3.29, 95% CI, -4.49 to 
      2.09; P < 0.00001); the decrease was even more remarkable in the LV end-systolic
      index after BMC transplantation in the group with LVEF <= 50% (WMD = -5.25, 95%
      CI, -9.30 to -1.20; P = 0.01), as well as in patients who received a dose of 10^7
      10^8 cells (WMD = -12.99, 95% CI, -19.07 to -6.91; P < 0.0001). In the group with
      a follow-up of more than 12 months, this beneficial effect was significant and
      increased to a more pronounced effect of +3.58% (95% CI, 1.55 to 5.61; P =
      0.0006) when compared with control. CONCLUSIONS: In this meta-analysis, BMC
      transfer at 3 to 7 days post-AMI was superior to transfer within 24 hours or more
      than 7 days after AMI in improving LVEF and decreasing LV end-systolic dimensions
      or LV end-diastolic dimensions. It is more effective in patients with lower
      baseline LVEF (<=50%) and the effect can last more than 12 months.

PMID- 29037257
TI  - Ventriculoperitoneal shunt insertion for hydrocephalus in human immunodeficiency
      virus-infected adults: a systematic review and meta-analysis protocol.
AB  - BACKGROUND: Hydrocephalus is a recognised complication of human immunodeficiency
      virus (HIV)-related opportunistic infections. Symptomatic raised cerebrospinal
      fluid pressure can be treated with ventriculoperitoneal shunt insertion (VPS). In
      HIV-infected patients however, there is a concern that VPS might be associated
      with unacceptably high rates of mortality. We aim to systematically review and
      appraise published literature to determine reported outcomes and identify
      predictors of outcome following VPS in relevant subgroups of HIV-infected adults.
      METHODS: The following electronic databases will be searched: The Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), EMBASE, CINAHL
      (EBSCOhost), LILACS (BIREME), Research Registry ( www.researchregistry.com ), the
      metaRegister of Controlled Trials (mRCT) ( www.controlled-trials.com ),
      ClinicalTrials.gov ( www.clinicaltrials.gov ) and OpenSIGLE database. Any
      randomised studies, cohort studies, case-control studies, interrupted time series
      or sequential case series reporting survival following VPS in HIV-infected
      individuals will be included. If high-quality homogenous studies exist, meta
      analysis will be conducted to determine 1-, 6- and 12-month mortality with
      comparison made between underlying aetiologies of hydrocephalus. DISCUSSION AND
      CONCLUSION: This study will generate a comprehensive review of VPS in HIV
      infected patients for publication. The primary outcome of meta-analysis is 12
      month survival. If only low-quality, heterogeneous studies are available, this
      study will demonstrate this deficiency and will be of value in justifying and
      aiding the design of future studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42016052239.

PMID- 29037258
TI  - Transplantation of Isl1+ cardiac progenitor cells in small intestinal submucosa
      improves infarcted heart function.
AB  - BACKGROUND: Application of cardiac stem cells combined with biomaterial scaffold
      is a promising therapeutic strategy for heart repair after myocardial infarction.
      However, the optimal cell types and biomaterials remain elusive. METHODS: In this
      study, we seeded Isl1+ embryonic cardiac progenitor cells (CPCs) into
      decellularized porcine small intestinal submucosa extracellular matrix (SIS-ECM)
      to assess the therapeutic potential of Isl1+ CPCs and the biocompatibility of SIS
      ECM with these cells. RESULTS: We observed that SIS-ECM supported the viability
      and attachment of Isl1+ CPCs. Importantly, Isl1+ CPCs differentiated into
      cardiomyocytes and endothelial cells 7 days after seeding into SIS-ECM. In
      addition, SIS-ECM with CPC-derived cardiomyocytes showed spontaneous contraction
      and responded to beta-adrenergic stimulation. Next, patches of SIS-ECM seeded
      with CPCs for 7 days were transplanted onto the outer surface of infarcted
      myocardium in mice. Four weeks after transplantation, the patches were tightly
      attached to the surface of the host myocardium and remained viable.
      Transplantation of patches improved cardiac function, decreased the left
      ventricular myocardial scarring area, and reduced fibrosis and heart failure.
      CONCLUSIONS: Transplantation of Isl1+ CPCs seeded in SIS-ECM represents an
      effective approach for cell-based heart therapy.

PMID- 29037259
TI  - Immuno-thermal ablations - boosting the anticancer immune response.
AB  - The use of immunomodulation to treat malignancies has seen a recent explosion in
      interest. The therapeutic appeal of these treatments is far reaching, and many
      new applications continue to evolve. In particular, immune modulating drugs have
      the potential to enhance the systemic anticancer immune effects induced by
      locoregional thermal ablation. The immune responses induced by ablation
      monotherapy are well documented, but independently they tend to be incapable of
      evoking a robust antitumor response. By adding immunomodulators to traditional
      ablative techniques, several researchers have sought to amplify the induced
      immune response and trigger systemic antitumor activity. This paper summarizes
      the work done in animal models to investigate the immune effects induced by the
      combination of ablative therapy and immunomodulation. Combination therapy with
      radiofrequency ablation, cryoablation, and microwave ablation are all reviewed,
      and special attention has been paid to the addition of checkpoint blockades.

PMID- 29037260
TI  - A novel protein derived from lamprey supraneural body tissue with efficient
      cytocidal actions against tumor cells.
AB  - BACKGROUND: In previous research, we found that cell secretion from the adult
      lamprey supraneural body tissues possesses cytocidal activity against tumor
      cells, but the protein with cytocidal activity was unidentified. METHODS: A novel
      lamprey immune protein (LIP) as defense molecule was first purified and
      identified in jawless vertebrates (cyclostomes) using hydroxyapatite column and Q
      Sepharose Fast Flow column. After LIP stimulation, morphological changes of tumor
      cells were analysed and measured whether in vivo or in vitro. RESULTS: LIP
      induces remarkable morphological changes in tumor cells, including cell blebbing,
      cytoskeletal alterations, mitochondrial fragmentation and endoplasmic reticulum
      vacuolation, and most of the cytoplasmic and organelle proteins are released
      following treatment with LIP. LIP evokes an elevation of intracellular calcium
      and inflammatory molecule levels. Our analysis of the cytotoxic mechanism
      suggests that LIP can upregulate the expression of caspase 1, RIPK1, RIP3 to
      trigger pyroptosis and necroptosis. To examine the effect of LIP in vivo, tumor
      xenograft experiments were performed, and the results indicated that LIP inhibits
      tumor growth without damage to mice. In addition, the cytotoxic action of LIP
      depended on the phosphatidylserine (PS) content of the cell membrane.
      CONCLUSIONS: These observations suggest that LIP plays a crucial role in tumor
      cell survival and growth. The findings will also help to elucidate the mechanisms
      of host defense in lamprey.

PMID- 29037263
TI  - Long-term effects of allergen-specific subcutaneous immunotherapy for house dust
      mite induced allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis is strongly associated with the presence of house
      dust mites. This study investigated the long-term effects of allergen-specific
      immunotherapy. Allergen-specific immunotherapy was applied over three years. The
      study was based on a 10-year follow up of patients with allergic rhinitis.
      METHODS: The study was conducted between 2001 and 2015. Skin prick test results
      and symptom scores were evaluated before (26 patients) and after 3 years (20
      patients) of allergen-specific immunotherapy (using data from a previously
      published study), and 10 years after allergen-specific immunotherapy had ended
      (20 of 26 patients). RESULTS: The symptom scores before allergen-specific
      immunotherapy were significantly higher than those obtained after 3 years of
      allergen-specific immunotherapy and 10 years after allergen-specific
      immunotherapy (p 0.0175). CONCLUSION: Subcutaneous immunotherapy is an effective
      treatment for house dust mite induced allergic rhinitis.

PMID- 29037262
TI  - Molecular and virulence characterization of highly prevalent Streptococcus
      agalactiae circulated in bovine dairy herds.
AB  - Bovine mastitis caused by Streptococcus agalactiae continues to be one of the
      major veterinary and economic issues in certain areas of the world. The more
      prevalent S. agalactiae strains that cause bovine mastitis in China dairy farms
      belong to a number of bovine-adapted sequence types (STs) ST67, ST103 and ST568.
      However, it is unknown why these STs can emerge as highly prevalent clones in
      bovine dairy farms. Here, to determine if a variety of virulence characteristics
      were associated with these highly prevalent STs, the molecular and virulence
      characterization of 116 strains isolated from bovine, human, fish and environment
      were analyzed. Our data showed that all bovine-adapted strains could be assigned
      to capsular genotype Ia or II, and carried pilus island 2b, and lactose operon.
      Importantly, we demonstrated that the growth ability in milk, biofilm formation
      ability and adhesion ability to bovine mammary epithelial cells (BMECs) were
      significantly higher for all bovine-adapted strains compared to strains from
      other origins. Additionally, ST103 and ST568 strains exhibited significantly
      higher hemolytic activity and cytotoxicity than ST67 strains. In conclusion, our
      study provides substantial evidence for the hypothesis that the virulence
      characteristics including efficient growth in milk, elevated biofilm formation
      ability, together with strong adhesion ability might have favored the high
      prevalence of the STs in the bovine environment, whereas the hemolytic activity
      and cytotoxicity were not the crucial characteristics.

PMID- 29037264
TI  - Cold acclimation increases cold tolerance independently of diapause programing in
      the bean bug, Riptortus pedestris.
AB  - The bean bug (Riptortus pedestris) is a pest of soybeans and other legumes in
      Japan and other Asian countries. It enters a facultative adult diapause on
      exposure to short days. While photoperiodism and diapause are well understood in
      R. pedestris, knowledge of cold tolerance is very limited, as is information on
      the effect of diapause on cold tolerance. We examined the effect of photoperiod,
      cold acclimation, and feeding status on cold tolerance in R. pedestris. We found
      that cold acclimation significantly increased survival at -10 degrees C in both
      long- and short-day adult R. pedestris. Since the difference in cold survival
      between long- and short-day cold-acclimated groups was only marginal, we conclude
      that entering diapause is not crucial for R. pedestris to successfully pass
      through cold acclimation and become cold tolerant. We observed similar effects in
      5th instar nymphs, with both long- and short-day cold-acclimated groups surviving
      longer cold exposures compared with non-acclimated groups. Starvation, which was
      tested only in adult bugs, had only a negligible and negative impact on cold
      survival. Although cold tolerance significantly increased with cold acclimation
      in adult bugs, supercooling capacity unexpectedly decreased. Our results suggest
      that changes in supercooling capacity as well as in water content are unrelated
      to cold tolerance in R. pedestris. An analysis of metabolites revealed
      differences between the treatments, and while several metabolites markedly
      increased with cold acclimation, their concentrations were too low to have a
      significant effect on cold tolerance.

PMID- 29037261
TI  - Distinct deposition of amyloid-beta species in brains with Alzheimer's disease
      pathology visualized with MALDI imaging mass spectrometry.
AB  - Amyloid beta (Abeta) deposition in the brain is an early and invariable feature
      of Alzheimer's disease (AD). The Abeta peptides are composed of about 40 amino
      acids and are generated from amyloid precursor proteins (APP), by beta- and gamma
      secretases. The distribution of individual Abeta peptides in the brains of aged
      people, and those suffering from AD and cerebral amyloid angiopathy (CAA), is not
      fully characterized. We employed the matrix-assisted laser desorption/ionization
      imaging mass spectrometry (MALDI-IMS) to illustrate the spatial distribution of a
      broad range of Abeta species in human autopsied brains. With technical
      advancements such as formic acid pretreatment of frozen autopsied brain samples,
      we have: i) demonstrated that Abeta1-42 and Abeta1-43 were selectively deposited
      in senile plaques while full-length Abeta peptides such as Abeta1-36, 1-37, 1-38,
      1-39, 1-40, and Abeta1-41 were deposited in leptomeningeal blood vessels. ii)
      Visualized distinct depositions of N-terminal truncated Abeta40 and Abeta42,
      including pyroglutamate modified at Glu-3 (N3pE), only with IMS for the first
      time. iii) Demonstrated that one single amino acid alteration at the C-terminus
      between Abeta1-42 and Abeta1-41 results in profound changes in their distribution
      pattern. In vitro, this can be attributed to the difference in the self
      aggregation ability amongst Abeta1-40, Abeta1-41, and Abeta1-42. These
      observations were further confirmed with immunohistochemistry (IHC), using the
      newly developed anti-Abeta1-41 antibody. Here, distinct depositions of truncated
      and/or modified C- and N-terminal fragments of Abetas in AD and CAA brains with
      MALDI-IMS were visualized in a spacio-temporal specific manner. Specifically,
      Abeta1-41 was detected both with MALDI-IMS and IHC suggesting that a single amino
      acid alteration at the C-terminus of Abeta results in drastic distribution
      changes. These results suggest that MALDI-IMS could be used as a standard
      approach in combination with clinical, genetic, and pathological observations in
      understanding the pathology of AD and CAA.

PMID- 29037265
TI  - Does skeletal muscle carnitine availability influence fuel selection during
      exercise?
AB  - Fat and carbohydrate are the major fuel sources utilised for oxidative,
      mitochondrial ATP resynthesis during human skeletal muscle contraction. The
      relative contribution of these two substrates to ATP resynthesis and total energy
      expenditure during exercise can vary substantially, and is predominantly
      determined by fuel availability and exercise intensity and duration. For example,
      the increased ATP demand that occurs with an increase in exercise intensity is
      met by increases in both fat and carbohydrate oxidation up to an intensity of
      approximately 60-70 % of maximal oxygen consumption. When exercise intensity
      increases beyond this workload, skeletal muscle carbohydrate utilisation is
      accelerated, which results in a reduction and inhibition of the relative and
      absolute contribution of fat oxidation to total energy expenditure. However, the
      precise mechanisms regulating muscle fuel selection and underpinning the decline
      in fat oxidation remain unclear. This brief review will primarily address the
      theory that a carbohydrate flux-mediated reduction in the availability of muscle
      carnitine to the mitochondrial enzyme carnitine palmitoyltransferase 1, a rate
      limiting step in mitochondrial fat translocation, is a key mechanism for the
      decline in fat oxidation during high-intensity exercise. This is discussed in
      relation to recent work in this area investigating fuel metabolism at various
      exercise intensities and taking advantage of the discovery that skeletal muscle
      carnitine content can be nutritionally increased in vivo in human subjects.

PMID- 29037266
TI  - Is cognitive-behavioural therapy more effective than relaxation therapy in the
      treatment of anxiety disorders? A meta-analysis.
AB  - BACKGROUND: It is not clear whether relaxation therapies are more or less
      effective than cognitive and behavioural therapies in the treatment of anxiety.
      The aims of the present study were to examine the effects of relaxation
      techniques compared to cognitive and behavioural therapies in reducing anxiety
      symptoms, and whether they have comparable efficacy across disorders. METHOD: We
      conducted a meta-analysis of 50 studies (2801 patients) comparing relaxation
      training with cognitive and behavioural treatments of anxiety. RESULTS: The
      overall effect size (ES) across all anxiety outcomes, with only one combined ES
      in each study, was g = -0.27 [95% confidence interval (CI) = -0.41 to -0.13],
      favouring cognitive and behavioural therapies (number needed to treat = 6.61).
      However, no significant difference between relaxation and cognitive and
      behavioural therapies was found for generalized anxiety disorder, panic disorder,
      social anxiety disorder and specific phobias (considering social anxiety and
      specific phobias separately). Heterogeneity was moderate (I2 = 52; 95% CI = 33
      65). The ES was significantly associated with age (p < 0.001), hours of cognitive
      and/or behavioural therapy (p = 0.015), quality of intervention (p = 0.007),
      relaxation treatment format (p < 0.001) and type of disorder (p = 0.008),
      explaining an 82% of variance. CONCLUSIONS: Relaxation seems to be less effective
      than cognitive and behavioural therapies in the treatment of post-traumatic
      stress disorder, and obsessive-compulsive disorder and it might also be less
      effective at 1-year follow-up for panic, but there is no evidence that it is less
      effective for other anxiety disorders.

PMID- 29037267
TI  - Tracking of infant and young child feeding practices among 9- to 24-month-old
      children in Nepal: the MAL-ED Birth Cohort Study.
AB  - OBJECTIVE: The present study aimed to assess infant and young child feeding
      (IYCF) practices and the tracking of dietary diversity score (DDS), intakes of Fe
      and vitamin A-rich foods and meal frequency in a peri-urban area in Nepal.
      Furthermore, to explore whether sociodemographic factors were associated with
      tracking patterns of these IYCF practices. DESIGN: Longitudinal study. Monthly
      food intake was measured by 24 h recall. Four time slots were used (9-12, 13-16,
      17-20 and 21-24 months). Tracking of IYCF practices was investigated using
      generalized estimating equations (GEE) models and Cohen's weighted kappa.
      Multinominal logistic regression was used to identify determinants for tracking
      of the IYCF practices. SETTING: Bhaktapur municipality, Nepal. SUBJECTS: Children
      (n 229) aged 9-24 months, randomly selected. RESULTS: Prevalence of minimum meal
      frequency was higher than for minimum dietary diversity at all time slots.
      Tracking based on absolute measures (GEE models) was moderate for DDS (0.48) and
      meal frequency (0.53), and low for intakes of Fe- (0.23) and vitamin A-rich
      (0.35) foods. Tracking based on rank measured was moderate for DDS and meal
      frequency, and fair for Fe- and vitamin A-rich foods. Low socio-economic status
      significantly increased the odds (OR; 95 % CI) of tracking of low v. high DDS
      (3.31; 1.44, 7.60) and meal frequency (3.46; 1.54, 7.76). CONCLUSIONS: Low
      tracking for intakes of Fe- and vitamin A-rich foods implies that interventions
      to improve these IYCF practices must address underlying causes for irregular
      intake to have sustainable effects.

PMID- 29037268
TI  - Probiotics, prebiotics, synbiotics and insulin sensitivity.
AB  - Animal studies indicate that the composition of gut microbiota may be involved in
      the progression of insulin resistance to type 2 diabetes. Probiotics and/or
      prebiotics could be a promising approach to improve insulin sensitivity by
      favourably modifying the composition of the gut microbial community, reducing
      intestinal endotoxin concentrations and decreasing energy harvest. The aim of the
      present review was to investigate the effects of probiotics, prebiotics and
      synbiotics (a combination of probiotics and prebiotics) on insulin resistance in
      human clinical trials and to discuss the potential mechanisms whereby probiotics
      and prebiotics improve glucose metabolism. The anti-diabetic effects of
      probiotics include reducing pro-inflammatory cytokines via a NF-kappaB pathway,
      reduced intestinal permeability, and lowered oxidative stress. SCFA play a key
      role in glucose homeostasis through multiple potential mechanisms of action.
      Activation of G-protein-coupled receptors on L-cells by SCFA promotes the release
      of glucagon-like peptide-1 and peptide YY resulting in increased insulin and
      decreased glucagon secretion, and suppressed appetite. SCFA can decrease
      intestinal permeability and decrease circulating endotoxins, lowering
      inflammation and oxidative stress. SCFA may also have anti-lipolytic activities
      in adipocytes and improve insulin sensitivity via GLUT4 through the up-regulation
      of 5'-AMP-activated protein kinase signalling in muscle and liver tissues.
      Resistant starch and synbiotics appear to have favourable anti-diabetic effects.
      However, there are few human interventions. Further well-designed human clinical
      studies are required to develop recommendations for the prevention of type 2
      diabetes with pro- and prebiotics.

PMID- 29037269
TI  - Prevalence of prediabetes and modifiable factors in an ethnic group of Mexico:
      the Comcaac Project.
AB  - OBJECTIVE: To determine the prevalence of and modifiable factors associated with
      prediabetes in the Comcaac Indians. DESIGN: Cross-sectional study where
      prediabetes was defined using fasting plasma glucose, 2 h plasma glucose and
      glycated Hb (HbA1c). Physical, anthropometric and biochemical measurements,
      medical record, socio-economic, dietary and physical activity information were
      collected. The modifiable factors associated with prediabetes were assessed using
      multiple logistic regression. Settings Comcaac Indian communities of Punta Chueca
      and El Desemboque, Sonora, Mexico. SUBJECTS: Adults (n 227) aged 20 years or
      older. RESULTS: The sex- and age-adjusted prevalence (95 % CI) of prediabetes was
      47.1 (40.8, 53.5) % in the overall population; age-adjusted prevalence was 47.3
      (35.6, 59.0) % in men and 46.7 (39.1, 54.3) % in women. The modifiable factors
      associated with a risk of prediabetes (OR; 95 % CI) were light-intensity physical
      activity (per 1 h/week increase: 1.04; 1.01, 1.07) and insulin resistance
      (homeostasis model assessment of insulin resistance score >6.1 v. <4.1: 4.62;
      1.37, 15.51). Increased consumption of a traditional dietary pattern based on
      fish and seafood, low-fat cereals, fruits and vegetables was a protective factor
      (0.49; 0.31, 0.79). All variables were modelled together and adjusted for age and
      sex. CONCLUSIONS: The high prediabetes prevalence found in the Comcaac community
      is alarming because it represents a large number of people who are at risk for
      type 2 diabetes. The identification of modifiable factors associated with
      prediabetes that are specific to this population may be useful for designing
      effective strategies to prevent prediabetes.

PMID- 29037270
TI  - Micron-Scale Deformation: A Coupled In Situ Study of Strain Bursts and Acoustic
      Emission.
AB  - Plastic deformation of micron-scale crystalline materials differs considerably
      from bulk samples as it is characterized by stochastic strain bursts. To obtain a
      detailed picture of the intermittent deformation phenomena, numerous micron-sized
      specimens must be fabricated and tested. An improved focused ion beam fabrication
      method is proposed to prepare non-tapered micropillars with excellent control
      over their shape. Moreover, the fabrication time is less compared with other
      methods. The in situ compression device developed in our laboratory allows high
      accuracy sample positioning and force/displacement measurements with high data
      sampling rates. The collective avalanche-like motion of the dislocations is
      observed as stress decreases on the stress-strain curves. An acoustic emission
      (AE) technique was employed for the first time to study the deformation behavior
      of micropillars. The AE technique provides important additional in situ
      information about the underlying processes during plastic deformation and is
      especially sensitive to the collective avalanche-like motion of the dislocations
      observed as the stress decreases on the deformation curves.

PMID- 29037271
TI  - Trajectories of caregiver burden in families of adult cystic fibrosis patients.
AB  - OBJECTIVES: Little is known about the experience of family caregivers of adults
      with cystic fibrosis (CF). This information is important for the identification
      of caregivers at risk for burden. METHODS: This was a longitudinal analysis of
      survey data obtained from caregivers of adult CF patients participating in an
      early intervention palliative care trial. Caregivers completed the validated
      Brief Assessment Scale for Caregivers (BASC) repeatedly over a 28-month period.
      Mixed-effects modeling evaluated multivariate associations with positive and
      negative caregiver perceptions over time. RESULTS: Of the 54 caregivers, 47.9%
      were spouses. The mean age was 50.9 years (SD = 13.2); 72.2% were women; 75.9%
      were married; and 63.0% were employed. At baseline, the BASC revealed large
      variations in positive and negative perceptions of caregiving. Although average
      scores over time were unchanging, variation was greater across caregivers than
      within caregivers (0.49 vs. 0.27, respectively). At baseline, the positive impact
      of caregiving in the sample was higher than the negative impact. Multivariate
      analysis revealed that patients' baseline pulmonary function and their full-time
      employment status predicted caregiver burden over time. SIGNIFICANCE OF RESULTS:
      Caregivers of CF patients varied in their positive and negative caregiving
      experiences, although burden levels in individual caregivers were stable over
      time. When the disease was advanced, caregivers of CF patients experienced more
      overall burden but also more positive impact. This suggests that the role of
      caregivers may become more meaningful as disease severity worsens. In addition,
      full-time patient employment was associated with lower caregiver burden
      regardless of disease severity. This suggests that burden in CF caregivers may be
      predicted by financial strain or benefits conferred by patient employment. These
      associations require further investigation to determine whether highly burdened
      caregivers can be identified and assisted using tailored interventions.

PMID- 29037272
TI  - Affective and Cognitive Verbal Theory of Mind in Schizophrenia: Results From a
      Novel Paradigm.
AB  - OBJECTIVES: Impairments of Theory of Mind (ToM) have been repeatedly demonstrated
      in patients with schizophrenia (SCZ). However, only a handful of studies have
      explored deficits in affective and cognitive subcomponents of ToM. Thus, this
      study aims to examine affective and cognitive ToM abilities in SCZ by using a
      novel, verbal paradigm. METHODS: Twenty-four SCZ and 22 healthy comparison
      subjects (HC) completed a battery of tasks, which consisted of: (i) Brief
      Cognitive Assessment Tool for Schizophrenia (B-CATS), (ii) three well-established
      tasks measuring social cognitive abilities, and (iii) original tasks which assess
      ability to infer cognitive and affective mental states based on everyday verbal
      social interactions. RESULTS: In line with previous findings, SCZ were
      outperformed by HC in all tasks. However, the interaction effect of the group and
      the task showed that cognitive (as opposed to affective) ToM was more profoundly
      impaired in patients with SCZ. CONCLUSIONS: It is proposed that in SCZ group
      cognitive ToM is more impaired as it involves more effortful reflective
      processes, while affective ToM, which is more automatic and based on reflexive
      processes, may differentiate patients from healthy comparison subjects to a
      lesser extent. (JINS, 2018, 24, 305-309).

PMID- 29037273
TI  - Determinants of takeaway and fast food consumption: a narrative review.
AB  - Out-of-home foods (takeaway, take-out and fast foods) have become increasingly
      popular in recent decades and are thought to be a key driver in increasing levels
      of overweight and obesity due to their unfavourable nutritional content.
      Individual food choices and eating behaviours are influenced by many interrelated
      factors which affect the results of nutrition-related public health
      interventions. While the majority of research based on out-of-home foods comes
      from Australia, the UK and USA, the same issues (poor dietary habits and
      increased prevalence of non-communicable disease) are of equal concern for urban
      centres in developing economies undergoing 'nutrition transition' at a global
      scale. The present narrative review documents key facets, which may influence out
      of-home food consumption, drawn from biological, societal, environmental,
      demographic and psychological spheres. Literature searches were performed and
      references from relevant papers were used to find supplementary studies. Findings
      suggest that the strongest determinants of out-of-home food availability are
      density of food outlets and deprivation within the built environment; however,
      the association between socio-economic status and out-of-home food consumption
      has been challenged. In addition, the biological and psychological drives
      combined with a culture where overweight and obesity are becoming the norm makes
      it 'fashionable' to consume out-of-home food. Other factors, including age group,
      ethnicity and gender demonstrate contrasting effects and a lack of consensus. It
      is concluded that further consideration of the determinants of out-of-home food
      consumption within specific populations is crucial to inform the development of
      targeted interventions to reduce the impact of out-of-home foods on public
      health.

PMID- 29037274
TI  - Morphometric and molecular analyses of two digenean species from the mullet:
      Skrjabinolecithum spinosum n. sp. from the Russian southern Far East and
      Unisaccus tonkini n. sp. from Vietnam.
AB  - Adults of Skrjabinolecithum spinosum n. sp. were discovered in Mugil cephalus
      from the Gulf of Peter the Great in southern Far-East Russia. Additionally,
      adults of Unisaccus tonkini n. sp. were found in the intestine of Moolgarda
      cunnesius and Moolgarda seheli from the coastal waters of Cat Ba Island, Tonkin
      Bay, northern Vietnam. Skrjabinolecithum spinosum n. sp. possesses a larger body,
      and ventral and oral sucker size in comparison with Skrjabinolecithum vitellosum,
      a smaller pharynx size and body length/width rate ratio in comparison to
      Skrjabinolecithum pyriforme, a smaller body length and prepharynx size in
      comparison to Skrjabinolecithum lobolecitum and a smaller pharynx length and egg
      size in comparison to Skrjabinolecithum indicum and S. lobolecitum. The new
      species also differs from S. indicum, S. lobolecitum and S. vitellosum by the
      form of the testis, and from the last two species by the presence of a two
      branched intestine. The morphometric parameters of S. spinosum n. sp. are similar
      to those of Skrjabinolecithum spasskii. However, S. spinosum n. sp., unlike S.
      spasskii, has an armed hermaphroditic duct. Unisaccus tonkini n. sp. is similar
      to Unisaccus spinosus (Martin, 1973), Unisaccus brisbanensis (Martin, 1973) and
      Unisaccus overstreeti (Ahmad, 1987) in body size but differs in oral sucker,
      pharynx and hermaphroditic sac size from U. spinosus, and in ventral sucker and
      ovary size from U. brisbanensis and U. overstreeti. Bayesian phylogenetic
      analysis, based on combined data of internal transcribed spacer 2 (ITS2) and
      partial 28S rRNA gene sequences, confirmed the validity of S. spinosum n. sp. and
      U. tonkini n. sp. Analysis of interrelationships of the family Haploporidae,
      including molecular data on new species, showed that the Waretrematinae subfamily
      is more heterogeneous in comparison with Haploporinae and Forticulcitinae, and
      includes U. tonkini n. sp.

PMID- 29037275
TI  - Intergenerational transmission of family meal patterns from adolescence to
      parenthood: longitudinal associations with parents' dietary intake, weight
      related behaviours and psychosocial well-being.
AB  - OBJECTIVE: The present study examined longitudinal associations between four
      family meal patterns (i.e. never had regular family meals, started having regular
      family meals, stopped having regular family meals, maintained having regular
      family meals) and young adult parents' dietary intake, weight-related behaviours
      and psychosocial well-being. In addition, family meal patterns of parents were
      compared with those of non-parents. DESIGN: Analysis of data from the
      longitudinal Project EAT (Eating and Activity in Adolescents and Young Adults)
      study. Linear and logistic regressions were used to examine the associations
      between family meal patterns and parents' dietary intake, weight-related
      behaviours and psychosocial well-being. SETTING: School and in-home settings.
      SUBJECTS: At baseline (1998; EAT-I), adolescents (n 4746) from socio-economically
      and racially/ethnically diverse households completed a survey and anthropometric
      measurements at school. At follow-up (2015; EAT-IV), participants who were
      parents (n 726) and who were non-parents with significant others (n 618)
      completed an online survey. RESULTS: Young adult parents who reported having
      regular family meals as an adolescent and as a parent ('maintainers'), or who
      started having regular family meals with their own families ('starters'),
      reported more healthful dietary, weight-related and psychosocial outcomes
      compared with young adults who never reported having regular family meals
      ('nevers'; P<0.05). In addition, parents were more likely to be family meal
      starters than non-parents. CONCLUSIONS: Results suggest that mental and physical
      health benefits of having regular family meals may be realized as a parent
      whether the routine of regular family meals is carried forward from adolescence
      into parenthood, or if the routine is started in parenthood.

PMID- 29037276
TI  - Analysis of single nucleotide polymorphisms variation associated with important
      economic and computed tomography measured traits in Texel sheep.
AB  - Sheep are an important part of the global agricultural economy. Growth and meat
      production traits are significant economic traits in sheep. The Texel breed is
      the most popular terminal sire breed in the UK, mainly selected for muscle growth
      and lean carcasses. This is a study based on a genome-wide association approach
      that investigates the links between some economically important traits, including
      computed tomography (CT) measurements, and molecular polymorphisms in UK Texel
      sheep. Our main aim was to identify single nucleotide polymorphisms (SNP)
      associated with growth, carcass, health and welfare traits of the Texel sheep
      breed. This study used data from 384 Texel rams. Data comprised ten traits,
      including two CT measured traits. The phenotypic data were placed in four
      categories: growth traits, carcass traits, health traits and welfare traits. De
      regressed estimated breeding values (EBV) for these traits together with sire
      genotypes derived with the Ovine 50 K SNP array of Illumina were jointly analysed
      in a genome wide association analysis. Eight novel chromosome-wise significant
      associations were found for carcass, growth, health and welfare traits. Three
      significant markers were intronic variants and the remainder intergenic variants.
      This study is a first step to search for genomic regions controlling CT-based
      productivity traits related to body and carcass composition in a terminal sire
      sheep breed using a 50 K SNP genome-wide array. Results are important for the
      further development of strategies to identify causal variants associated with CT
      measures and other commercial traits in sheep. Independent studies are needed to
      confirm these results and identify candidate genes for the studied traits.

PMID- 29037277
TI  - Development and preliminary validation of the physician support of skin self
      examination scale.
AB  - Skin self-examination (SSE) is a crucial preventive health behaviour in melanoma
      survivors, as it facilitates early detection. Physician endorsement of SSE is
      important for the initiation and maintenance of this behaviour. This study
      focussed on the preliminary validation of a new nine-item measure assessing
      physician support of SSE in melanoma patients. English and French versions of
      this measure were administered to 188 patients diagnosed with melanoma in the
      context of a longitudinal study investigating predictors and facilitators of SSE.
      Structural validity was investigated using exploratory factor analysis conducted
      in Mplus and convergent and divergent validity was assessed using bivariate
      correlations conducted in spss. Results suggest that the scale is a
      unidimensional and reliable measure of physician support for SSE. Given the
      uncertainty regarding the optimal frequency of SSE for at-risk individuals, we
      recommend that future psychometric evaluations of this scale consider tailoring
      items according to the most up-to-date research on SSE effectiveness.

PMID- 29037278
TI  - Improving Skin Integrity in Babies Diagnosed with Neonatal Abstinence Syndrome.
AB  - Neonatal abstinence syndrome (NAS) is becoming a national epidemic. Neonates with
      NAS display myriad signs during withdrawal from the drugs they were exposed to in
      utero. One sign is skin excoriation, as well as other skin injuries. While care
      of the neonate experiencing NAS has been well documented in the literature, the
      care of the skin of that neonate has not. The purpose of this monograph is to
      discuss the current literature on neonatal abstinence syndrome, to describe the
      anatomy and physiology of neonatal skin, and to make recommendations for the
      prevention and care of the most common neonatal skin injuries seen in infants
      exhibiting NAS.

PMID- 29037279
TI  - Continuing Education Home Study Course...8.

PMID- 29037280
TI  - Screening of Chemical Dyes in Traditional Chinese Medicine by HPTLC-MS.
AB  - It has been uncovered that chemical dyes are illegally used in traditional
      Chinese medicines to brighten color and cover up inferiority, which threaten the
      safety of patients. In the present study, an HPTLC-MS method was developed for
      the effective screening of 11 chemical dyes (Sudan I, II, III, and IV; 808
      Scarlet; Sudan Red 7B; malachite green; Basic Orange 2; auramine; Orange II; and
      erythrosine) in traditional Chinese medicine (TCM) raw materials and Chinese
      patent medicines. Firstly, unwashed HPTLC plates were chosen by comparing the
      background signals of the TLC plates used directly and prewashed with analytical
      grade and HPLC grade solvents. Twice developments were conducted to isolate
      chemical dyes of different polarity. Possible adulterants were preliminarily
      identified by comparing Rf values and in situ UV-Vis spectra with those of the
      references. Further confirmation was conducted by tandem MS analysis via an
      elution head-based TLC-MS interface. Sudan I and IV, 808 Scarlet, and Orange II
      were successfully detected in eight batches of TCM. The proposed method could be
      applied as a reliable technology for the screening of chemical dyes in TCM.

PMID- 29037281
TI  - Conference Proceedings-Poster Abstracts, San Diego, CA.

PMID- 29037283
TI  - Abstracts from the 15th National Neonatal Nurses Conference and 18th National
      Mother Baby Nurses Conference Orlando FL, September 17-19, 2015.

PMID- 29037285
TI  - Continuing Education Course.

PMID- 29037286
TI  - Do rats pass the sniff test?

PMID- 29037287
TI  - Provision of ART to individuals infected with HIV: impact on the epidemiology and
      control of tuberculosis.

PMID- 29037288
TI  - Global asthma burden and poverty in the twenty-first century.

PMID- 29037289
TI  - Conducting high-quality tuberculosis clinical trials in China: opportunities and
      challenges.
AB  - Tuberculosis (TB) is an ancient disease that is a devastating threat to public
      health. As the country with the second highest number of TB cases and the highest
      number of multidrug-resistant TB cases in the world, China is now striving to be
      at the forefront of TB research and drug development. This article is based on
      the observations made by the authors during the recent partnership initiative
      between the National Institutes of Health and the Chinese TB community, as well
      as an extensive literature review. The article examines the advantages and
      challenges of conducting large-scale international multicenter TB clinical trials
      in China. China is becoming an excellent location for new TB drug trials,
      especially in collaboration with international organizations that bring
      considerable technical assistance, quality control, training, and oversight with
      these partnerships.

PMID- 29037290
TI  - Onions and prevalence surveys: how to analyze and quantify tuberculosis case
      finding gaps.
AB  - Finding the missing 4 million tuberculosis (TB) patients is one of the greatest
      challenges facing the TB community. The optimal approaches to this will vary by
      country, but there is no consistent process for analyzing the potential benefit
      of different strategies, or for deciding which approaches are most appropriate
      for a given setting. Here, I bring together the Onion Model-as a way to think
      through health system structures-and evidence from prevalence surveys. The result
      is a structured process for prioritizing different strategies for case finding.
      Outcomes vary widely by setting, pointing to the importance of each country
      undertaking such a prioritization process.

PMID- 29037291
TI  - The devil we know: is the use of injectable agents for the treatment of MDR-TB
      justified?
AB  - For decades, second-line injectable agents (IAs) have been the cornerstone of
      treatment for multidrug-resistant tuberculosis (MDR-TB). Although evidence on the
      efficacy of IAs is limited, there is an expanding body of evidence on the serious
      adverse events caused by these drugs. Here, we present the results of a
      structured literature review of the safety and efficacy of IAs. We review the
      continued widespread use of these agents in the context of therapeutic
      alternatives-most notably the newer TB drugs, bedaquiline and delamanid-and from
      the context of human rights, ethics and patient-centered care. We conclude that
      there is limited evidence of the efficacy of IAs, clear evidence of the risks of
      these drugs, and that persons living with MDR-TB should be informed about these
      risks and provided with access to alternative therapeutic options.

PMID- 29037292
TI  - Accuracy of giant African pouched rats for diagnosing tuberculosis: comparison
      with culture and Xpert(r) MTB/RIF.
AB  - SETTING: Enhanced tuberculosis (TB) case finding using detection rats in
      Tanzania. OBJECTIVES: To assess the diagnostic accuracy of detection rats
      compared with culture and Xpert(r) MTB/RIF, and to compare enhanced case-finding
      algorithms using rats in smear-negative presumptive TB patients. DESIGN: A fully
      paired diagnostic accuracy study in which sputum of new adult presumptive TB
      patients in Tanzania was tested using smear microscopy, 11 detection rats,
      culture and Xpert. RESULTS: Of 771 eligible participants, 345 (45%) were culture
      positive for Mycobacterium tuberculosis, and 264 (34%) were human
      immunodeficiency virus (HIV) positive. The sensitivity of the detection rats was
      up to 75.1% (95%CI 70.1-79.5) when compared with culture, and up to 81.8% (95%CI
      76.0-86.5) when compared with Xpert, which was statistically significantly higher
      than the sensitivity of smear microscopy. Corresponding specificity was 40.6%
      (95%CI 35.9-45.5) compared with culture. The accuracy of rat detection was
      independent of HIV status. Using rats for triage, followed by Xpert, would result
      in a statistically higher yield than rats followed by light-emitting diode
      fluorescence microscopy, whereas the number of false-positives would be
      significantly lower than when using Xpert alone. CONCLUSION: Although detection
      rats did not meet the accuracy criteria as standalone diagnostic or triage
      testing for presumptive TB, they have additive value as a triage test for
      enhanced case finding among smear-negative TB patients if more advanced
      diagnostics are not available.

PMID- 29037293
TI  - Community-based active case finding for tuberculosis in rural western China: a
      cross-sectional study.
AB  - SETTING: Current passive case finding strategies are not effective at identifying
      tuberculosis (TB) patients in rural China. OBJECTIVE: To evaluate a community
      based, active case finding (ACF) scheme in identifying symptomatic individuals
      with TB. DESIGN: We conducted door-to-door household visits of all residents aged
      ?15 years at two rural sites to screen for TB symptoms. Individuals with symptoms
      were enrolled and asked to provide three sputum samples. All participants
      underwent chest X-ray, and microbiologic detection of Mycobacterium tuberculosis
      from sputum samples using microscopy, solid culture and Xpert(r) MTB/RIF was
      performed. RESULTS: Among the 19 334 residents screened for TB symptoms, 865
      (4.5%) reported having ?1 symptom. A total of 52 TB cases were detected, 11 of
      whom had microbiologic confirmation. Xpert identified all five M. tuberculosis
      culture-positive cases and yielded an additional three diagnoses. Prevalence of
      newly detected TB at the two sites through ACF was respectively 475 and 196 per
      100 000 population. These estimates are respectively four and eight times, on
      average, higher than those identified through passive surveillance during the
      previous 5-year period for the two sites. CONCLUSION: Community-based symptom
      screening followed by laboratory tests was found to be feasible and effective in
      increasing TB case finding in rural China.

PMID- 29037294
TI  - Diagnostic yield of active case finding for tuberculosis and HIV at the household
      level in slums in Haiti.
AB  - SETTING: Haiti has the highest burden of tuberculosis (TB) in the Americas, with
      an estimated prevalence of 254 per 100 000 population. The Haitian Group for the
      Study of Kaposi's Sarcoma and Opportunistic Infections (Groupe Haitien d'Etude du
      Sarcome de Kaposi et des Infections Opportunistes, GHESKIO) conducted active case
      finding (ACF) for TB at the household level in nine slums in Port-au-Prince.
      OBJECTIVE: We report on the prevalence of undiagnosed TB detected through
      GHESKIO's ACF campaign. DESIGN: From 1 August 2014 to 31 July 2015, we conducted
      a retrospective cohort analysis using GHESKIO's ACF campaign data. All
      individuals who reported chronic cough (cough ?2 weeks) were tested for TB at
      GHESKIO, and those aged ?10 years were included in the analyses. RESULTS: Of 104
      097 individuals screened in the community, 5598 (5%) reported chronic cough and
      satisfied the study inclusion criteria. A total of 1110 (20%) were diagnosed with
      active TB disease (prevalence of 1066/100 000). Of the 5472 (98%) patients tested
      for human immunodeficiency virus (HIV), 528 (10%) were HIV-positive; 143 (3%)
      patients were diagnosed with both diseases. CONCLUSION: Household-level screening
      for cough with TB and HIV testing for symptomatic patients was a high-yield
      strategy, leading to the detection of a prevalence of undiagnosed disease
      exceeding national estimates by more than four-fold for TB, and by five-fold for
      HIV.

PMID- 29037295
TI  - Does antiretroviral treatment increase the infectiousness of smear-positive
      pulmonary tuberculosis?
AB  - BACKGROUND: Understanding of the effects of human immunodeficiency virus (HIV)
      infection and antiretroviral treatment (ART) on Mycobacterium tuberculosis
      transmission dynamics remains limited. We undertook a cross-sectional study among
      household contacts of smear-positive pulmonary tuberculosis (TB) cases to assess
      the effect of established ART on the infectiousness of TB. METHOD: Prevalence of
      tuberculin skin test (TST) positivity was compared between contacts of index
      cases aged 2-10 years who were HIV-negative, HIV-positive but not on ART, on ART
      for <1 year and on ART for ?1 year. Random-effects logistic regression was used
      to take into account clustering within households. RESULTS: Prevalence of M.
      tuberculosis infection in contacts of HIV-negative patients, HIV-positive
      patients on ART ?1 year and HIV-positive patients not on ART/on ART <1 year index
      cases was respectively 44%, 21% and 22%. Compared to contacts of HIV-positive
      index cases not on ART or recently started on ART, the odds of TST positivity was
      similar in contacts of HIV-positive index cases on ART ?1 year (adjusted OR [aOR]
      1.0, 95%CI 0.3-3.7). The odds were 2.9 times higher in child contacts of HIV
      negative index cases (aOR 2.9, 95%CI 1.0-8.2). CONCLUSIONS: We found no evidence
      that established ART increased the infectiousness of smear-positive, HIV-positive
      index cases.

PMID- 29037296
TI  - Tuberculosis in recipients of solid-organ transplants during 1995-2015 in Cali,
      Colombia.
AB  - SETTING: Tuberculosis (TB) in solid-organ transplants (SOTs) is an important
      opportunistic infection associated with mortality and graft loss. SOT recipients
      carry a higher risk of contracting active TB than the general population.
      Clinical and radiographic presentations are non-specific, and sputum smear and
      culture have low yields. TB patients with SOTs require standard anti-tuberculosis
      treatment. However, rifampicin (RMP) use is associated with a 30% rate of acute
      graft rejection (AGR) and a 20% rate of transplant loss. OBJECTIVE: To determine
      treatment outcomes in SOT recipients with active TB. DESIGN: A retrospective
      study of clinical and microbiological data and TB treatment outcomes. RESULTS:
      Among the 2349 transplants assessed, active TB was detected in 31 recipients; 55%
      had pulmonary TB and 40% were sputum smear-positive. In 32% of the patients, TB
      was diagnosed 30 days after symptom onset, 77% of the patients were cured and 10%
      died. AGR occurred in 13%. CONCLUSION: TB was diagnosed in <30 days. Anti
      tuberculosis treatment without RMP (80% vs. 67%; P = 0.48, OR 0.5, 95%CI 0.07
      3.55) and with moxifloxacin yielded higher treatment success rates and a lower
      risk of AGR.

PMID- 29037297
TI  - Innovative approach to the design and evaluation of treatment adherence
      interventions for drug-resistant TB.
AB  - BACKGROUND: Drug-resistant tuberculosis (DR-TB) treatment is expensive, lengthy,
      and can cause severe side effects. Patients face socio-economic, psychosocial,
      and systemic barriers to adherence; poor adherence results in poor treatment
      outcomes. OBJECTIVE: To estimate the effects of the components of the information
      motivation-behavioral skills model on DR-TB treatment adherence. DESIGN: We
      recruited 326 adults receiving DR-TB treatment and 86 of their health care
      service providers from 40 health centers in Lima, Peru. The main outcome was
      adherence (i.e., the proportion of prescribed doses taken by a patient). Exposure
      measures were adherence information, motivation, and behavioral skills; loss to
      follow-up during previous TB treatment(s); providers' work engagement; and
      patient-perceived support from his/her social network. RESULTS: Structural
      equation modeling revealed that adherence information and motivation had positive
      effects on adherence, but only if mediated through behavioral skills (beta =
      0.02, P < 0.01 and beta = 0.07, P < 0.001, respectively). Behavioral skills had a
      direct positive effect on adherence (beta = 0.27, P < 0.001). Loss to follow-up
      during previous treatment had a direct negative effect, providers' work
      engagement had a direct positive effect, and perceived support had indirect
      positive effects on adherence. The model's overall R2 was 0.76. CONCLUSION: The
      components of the information-motivation-behavioral skills model were associated
      with adherence and could be used to design, monitor, and evaluate interventions
      targeting adherence to DR-TB treatment.

PMID- 29037298
TI  - Determinants of multidrug resistance among previously treated tuberculosis
      patients in Zimbabwe, 2014.
AB  - SETTING: Zimbabwe. OBJECTIVE: To investigate the determinants of multidrug
      resistant tuberculosis (MDR-TB) among previously treated TB patients. DESIGN: A
      1:3 case-control study with bivariate analysis and logistic regression. RESULTS:
      Risk factors for MDR-TB were history of nursing an MDR-TB patient (adjusted OR
      [aOR] 4.46, 95%CI 2.02-9.88), history of hospitalisation for ?3 days (aOR 2.91,
      95%CI 1.62-5.23) and history of foreign travel and stay outside Zimbabwe (aOR
      2.68, 95%CI 1.46-4.91). Protective factors were previous successful treatment
      (aOR 0.05, 95%CI 0.02-0.11), history of supervision by a health worker/village
      health worker (aOR 0.34, 95%CI 0.19-0.60) and having been treated not more than
      once previously for TB (aOR 0.18, 95%CI 0.08-0.38). No association between human
      immunodeficiency virus (HIV) infection and MDR-TB (aOR 1.00, 95%CI 0.53-1.88) was
      observed. However, among HIV-infected patients, those with CD4 <200 cells/mm3
      were more likely to develop MDR-TB (aOR 4.62, 95%CI 2.49-8.53). CONCLUSION:
      Individual, service-related, social and demographic factors interact to determine
      multidrug resistance among previously treated TB patients. Infection control,
      treatment adherence, reduction of side effects and drug susceptibility testing
      must be strengthened to reduce the MDR-TB burden in Zimbabwe.

PMID- 29037300
TI  - High-resolution computed tomography findings in chronic eosinophilic vs.
      cryptogenic organising pneumonia.
AB  - BACKGROUND: The similar clinical and computed tomography (CT) characteristics of
      cryptogenic organising pneumonia (COP) and chronic eosinophilic pneumonia (CEP)
      make precise diagnosis challenging. OBJECTIVES: To help differentiate between COP
      and CEP using high-resolution CT (HRCT). DESIGN: Clinical data and HRCT images of
      COP and CEP patients referred to Masih Daneshvari Hospital, Tehran, Iran, from
      2007 to 2015 were reviewed. Diagnosis of COP or CEP was confirmed using open lung
      biopsy or a combination of transbronchial biopsy, bronchoalveolar lavage fluid
      (BALF) analysis, peripheral eosinophilia and a favourable response to
      corticosteroids. RESULTS: Ground-glass opacity, a dominant ground-glass pattern,
      upper-lobe pneumonia, increased thickness of bronchial walls and a mosaic pattern
      in the lungs were more frequent in CEP. Lower-lobe pneumonia, subpleural
      reticulation, a dominant consolidation pattern, nodules and masses, non-septal
      linear opacities, bronchial dilation and a reverse halo sign were more frequent
      in COP. History of asthma, wheezing and peripheral eosinophilia was significantly
      more common in CEP than in COP. CONCLUSION: Distinguishing between CEP and COP
      based on HRCT alone is not always possible. However, in many cases, especially if
      the correct diagnosis cannot be established by other means, certain HRCT features
      can be very helpful.

PMID- 29037299
TI  - Time to treatment for rifampicin-resistant tuberculosis: systematic review and
      meta-analysis.
AB  - BACKGROUND: To reduce transmission and improve patient outcomes, rapid diagnosis
      and treatment of rifampicin-resistant tuberculosis (RR-TB) is required.
      OBJECTIVE: To conduct a systematic review and meta-analysis assessing time to
      treatment for RR-TB and variability using diagnostic testing methods and
      treatment delivery approach. DESIGN: Studies from 2000 to 2015 reporting time to
      second-line treatment initiation were selected from PubMed and published
      conference abstracts. RESULTS: From 53 studies, 83 cohorts (13 034 patients) were
      included. Overall weighted mean time to treatment from specimen collection was 81
      days (95%CI 70-91), and was shorter with ambulatory (57 days, 95%CI 40-74) than
      hospital-based treatment (86 days, 95%CI 71-102). Time to treatment was shorter
      with genotypic susceptibility testing (38 days, 95%CI 27-49) than phenotypic
      testing (108 days, 95%CI 98-117). The mean percentage of diagnosed patients
      initiating treatment was 76% (95%CI 70-83, range 25-100). CONCLUSION: Time to
      second-line anti-tuberculosis treatment initiation is extremely variable across
      studies, and often unnecessarily long. Reduced delays are associated with
      genotypic testing and ambulatory treatment settings. Routine monitoring of the
      proportion of diagnosed patients initiating treatment and time to treatment are
      necessary to identify areas for intervention.

PMID- 29037301
TI  - Asthma symptoms among Chinese children: the role of ventilation and PM10 exposure
      at school and home.
AB  - SETTING: Respiratory symptoms in relation to environment in Taiyuan, China.
      OBJECTIVE: To study associations between school/home exposure and prevalence of
      respiratory symptoms and self-reported respiratory infections (RIs) among
      students. DESIGN: A total of 2134 pupils from 10 schools answered a
      questionnaire; air pollution at school was measured. RESULTS: The prevalence of
      current wheeze, daytime attacks of breathlessness, nocturnal cough, nocturnal
      respiratory symptoms and RI was respectively 4.4%, 18.7%, 11.6%, 3.6% and 32.3%.
      Environmental tobacco smoke (ETS) at home was associated with daytime attacks of
      breathlessness (OR 1.41), nocturnal cough (OR 1.41) and RI (OR 1.26).
      Redecoration or indoor painting at home was associated with wheeze (OR 2.02),
      daytime attacks of breathlessness (OR 1.57) and nocturnal symptoms (OR 1.83).
      Dampness or mould at home was associated with daytime attacks of breathlessness
      (OR 1.68), nocturnal cough (OR 1.68) and RI (OR 1.69). Particulate matter of
      diameter ? 10 microns (PM10) in the classroom was associated with nocturnal cough
      (OR 1.20/10 MUg/m3). PM10 outside school was associated with daytime attacks of
      breathlessness (OR 1.07/10 MUg/m3) and nocturnal cough (OR 1.13/10 MUg/m3).
      Indoor carbon dioxide, a marker of poor ventilation (OR 1.52/1000 parts per
      million), and relative humidity (RH) (OR 1.33/10%) were associated with nocturnal
      cough. CONCLUSION: Dampness, redecoration and ETS at home, as well as poor
      ventilation flow, and high RH and PM10 concentration at school may influence
      respiratory health.

PMID- 29037302
TI  - FeNO levels increase with degree of sensitisation in apprentices at risk of
      occupational asthma.
AB  - BACKGROUND: Atopy has emerged as a major determinant of airway inflammation.
      OBJECTIVE: To examine whether early markers of occupational asthma increase with
      degree of sensitisation. METHOD: This study was a prospective follow-up study of
      apprentices in baking, pastry-cooking and hairdressing during their 2-year
      apprenticeship. Four visits were conducted to administer a standardised
      questionnaire, a methacholine challenge test to assess bronchial
      hyperresponsiveness (BHR) and to measure fractional exhaled nitric oxide (FeNO).
      Degree of sensitisation was estimated based on the number of positive skin prick
      tests (SPTs) for 12 common allergens. Mixed-effect models were applied to examine
      the association between the degree of sensitisation and FeNO levels, BHR and
      eosinophilic status (more than 3% of cells in nasal lavage fluid). RESULTS: Of
      the 441 apprentices who agreed to take part in the study, 417 had at least one
      SPT session providing usable results. Degree of sensitization was related to BHR
      and FeNO levels. Compared to non-sensitised subjects, FeNO levels were 83% higher
      (P < 0.01) in highly sensitised subjects and 30% higher (P < 0.01) in weakly
      sensitised subjects. However, the degree of sensitisation was not predictive of
      the evolution of these markers. CONCLUSION: Degree of sensitisation is related to
      early markers of airway inflammation.

PMID- 29037305
TI  - Putting urban Aboriginal and Torres Strait Islander food insecurity on the
      agenda.
AB  - Food insecurity adversely affects diet quality, physical, mental and social
      wellbeing and the capacity to act on health advice recommended by primary
      healthcare providers. In this article, an overview of the neglected issue of food
      insecurity in urban Aboriginal and Torres Strait Islander communities is
      provided. Policy and action on food security for urban Aboriginal and Torres
      Strait Islander people is reviewed, and it is argued that for primary health care
      to better address food insecurity, an evidence base is needed to understand the
      experiences of individuals and households and how to work effectively to support
      food insecure clients.

PMID- 29037303
TI  - Prevalence and impact of asthma among school-aged students in Lima, Peru.
AB  - SETTING AND OBJECTIVE: The International Study of Asthma and Allergies in
      Childhood (ISAAC) reported asthma prevalence in Peru to be among the highest in
      the world. We assessed the prevalence and morbidity of self-reported asthma in an
      underserved, peri-urban area of Lima, Peru, with limited medical access. DESIGN:
      The study was conducted in the outskirts of Lima from March to May 2011. Five
      hundred children aged 6-18 years were selected through cluster sampling. Parents
      completed a modified version of the ISAAC questionnaire. Children underwent
      spirometry testing. Those with a forced expiratory volume in one second (FEV1%
      predicted) ?80% were tested for reversibility using salbutamol. RESULTS: Of the
      500 children selected, 71% participated. The prevalence of asthma was 16.7%.
      Asthma symptoms were associated with self-reported asthma (P < 0.001); 52.5% of
      children with asthma had ever used an inhaler (P < 0.001), and 27.1% had never
      been to the doctor for respiratory problems (P < 0.001). CONCLUSION: We found a
      high prevalence of self-reported asthma and high morbidity related to asthma
      symptoms in the previous 12 months among the study cohort. Symptoms were poorly
      controlled due to limited availability of medication and access to medical
      services.

PMID- 29037306
TI  - Making Social Media Work for Your Practice.

PMID- 29037307
TI  - Effect of multiparity on bone mineral density, evaluated with bone turnover
      markers.
AB  - OBJECTIVE: Our aim was to investigate the effect of parity on osteoporosis by
      evaluating bone mineral density, markers of bone turn-over and other factors that
      are effective in osteoporosis in multiparous (five deliveries or more) and
      nulliparous women in the post-menopausal period. METHODS: A total of 91
      multiparous (five deliveries or more) and 31 nulliparous postmenopausal women
      were included in this study. All patients were interviewed on sociodemographic
      characteristics, gynecologic history, personal habits, levels of physical
      activity, and life-long intake of calcium. Bone mineral density was measured at
      lumbar (L1-4) and femoral neck regions with Dexa. RESULTS: The mean age of
      multiparous women was 58.79+/-7.85 years, and the mean age of nulliparous women
      was 55.84+/-7.51. The femoral BMD was 0.94+/-0.16 and lumbar BMD 1.01+/-0.16 in
      multiparous women, femoral BMD was 0.99+/-0.16 and lumbar BMD 1.07+/-0.14 in
      nulliparous women. There were no statistical differences between the femoral and
      lumbar T scores and BMD values of the two groups. Lumbar T scores and lumbar BMD
      showed a decrease with increasing total duration of breast-feeding in multiparous
      women. The independent risk factors for osteoporosis in the regression analysis
      of multiparous women were found to be the duration of menopause and body weight
      of 65kg and less. CONCLUSION: There is no difference between the bone mineral
      densities of multiparous and nulliparous women. Females with lower body-weight
      and longer duration of menopause should be followed-up more carefully for
      development of osteoporosis.

PMID- 29037308
TI  - Topographic MRI evaluation of the sacroiliac joints in patients with axial
      spondyloarthritis.
AB  - OBJECTIVE: To evaluate the imaging features of spondyloarthritis in magnetic
      resonance imaging (MRI) of the sacroiliac (SI) joint and topography (in thirds)
      and affected margin, considering that this issue is rarely addressed in the
      literature. METHODS: A cross-sectional study evaluating MRI (1.5T) of SI in 16
      patients with axial spondyloarthritis, for the presence of acute (subchondral
      bone edema, enthesitis, synovitis and capsulitis) and chronic (erosions,
      subchondral bone sclerosis, bony bridges, and fatty infiltration) changes,
      performed by two blinded radiologists. MRI findings were correlated with clinical
      data, including age, duration of disease, medications, HLA-B27, BASDAI, ASDAS-ESR
      and ASDAS-CRP, BASMI, BASFI, and mSASSS. RESULTS: Bone edema pattern and erosions
      were predominant in the upper third of SI (p=0.050 and p=0.0014, respectively).
      There was a correlation between disease duration and structural changes by
      affected third (p=0.028-0.037), as well as between the presence of bone bridges
      with BASMI (p=0.028) and mSASSS (p=0.014). Patients with osteitis in the lower
      third showed higher values for ASDAS (ESR: p=0.011 and PCR: p=0.017). CONCLUSION:
      Chronic inflammatory changes and the pattern of bone edema predominated in the
      upper third of SI, but a simultaneous involvement of middle or lower thirds of
      the joint was also noted. The location of involvement in the upper third of SI is
      insufficient to differentiate between degeneration and inflammation.

PMID- 29037309
TI  - Correlation between cellular expression of complement regulatory proteins with
      depletion and repopulation of B-lymphocytes in peripheral blood of patients with
      rheumatoid arthritis treated with rituximab.
AB  - OBJECTIVES: To correlate the basal expression of complement regulatory proteins
      (CRPs) CD55, CD59, CD35, and CD46 in B-lymphocytes from the peripheral blood of a
      cohort of 10 patients with rheumatoid arthritis (RA) initiating treatment with
      rituximab (RTX) with depletion and time repopulation of such cells. METHODS: Ten
      patients with RA received two infusions of 1g of RTX with an interval of 14 days.
      Immunophenotypic analysis for the detection of CD55, CD59, CD35, and CD46 on B
      lymphocytes was carried out immediately before the first infusion. The population
      of B-lymphocytes was analyzed by means of basal CD19 expression and after 1, 2,
      and 6 months after the infusion of RTX, and then quarterly until clinical
      relapse. Depletion of B-lymphocytes in peripheral blood was defined as a CD19
      expression <0.005*109/L. RESULTS: Ten women with a median of 49 years and a
      baseline DAS28=5.6 were evaluated; 9 were seropositive for rheumatoid factor.
      Five patients showed a repopulation of B-lymphocytes after 2 months, and the
      other five after 6 months. There was a correlation between the basal expression
      of CD46 and the time of repopulation (correlation coefficient=-0.733, p=0.0016).
      A similar trend was observed with CD35, but without statistical significance
      (correction coefficient=-0.522, p=0.12). CONCLUSION: The increased CD46
      expression was predictive of a faster repopulation of B-lymphocytes in patients
      treated with RTX. Studies involving a larger number of patients will be needed to
      confirm the utility of basal expression of CRPs as a predictor of clinical
      response.

PMID- 29037310
TI  - Latent tuberculosis infection screening in juvenile idiopathic arthritis patients
      preceding anti-TNF therapy in a tuberculosis high-risk country.
AB  - OBJECTIVES: To evaluate, in an endemic country, the long-term efficacy of latent
      tuberculosis infection (LTBI) screening and primary prophylaxis in patients with
      JIA receiving TNF blockers. METHODS: This was a retrospective cohort that
      included JIA patients eligible to anti-TNF therapy. Patients were screened for
      LTBI prior to anti-TNF using tuberculin skin test (TST), chest X-ray and history
      of exposure to TB. Subjects were regularly followed at 2-month intervals.
      RESULTS: Sixty-nine JIA patients with current age of 17.4+/-5.8 years, mean
      disease duration of 5.0+/-4.9 years were included. Forty-seven patients received
      a single anti-TNF, while 22 patients switched to another anti-TNF once or twice:
      57 were treated with etanercepte, 33 patients with adalimumab and 3 infliximab.
      LTBI screening was positive in three patients: one had TST-positive and history
      of TB exposure and two had solely TST-positive. No active TB was diagnosed during
      the study period (median of follow-up was 3.8 years). CONCLUSION: Long-term
      evaluation revealed that LTBI screening and primary prophylaxis before anti-TNF
      treatment was effective in a high-risk country and TST was the most sensitive
      parameter to identify these patients.

PMID- 29037311
TI  - Therapeutic plasma exchange in rheumatic diseases: a university hospital
      experience.
AB  - INTRODUCTION: Each day, evidence accumulates related to the use of therapeutic
      plasma exchange (TPE) in patients with rheumatic diseases. San Ignacio University
      Hospital has recorded all of the TPE sessions performed by the institution's
      apheresis group. OBJECTIVE: To describe the TPE experience of patients with
      rheumatologic diseases in a hospital setting. METHODS: Descriptive,
      observational, retrospective analysis. This study included analyses of the TPE
      sessions that were performed in patients with rheumatic diseases from November
      2009 to November 2013. RESULTS: The apheresis group performed 136 sessions in 27
      patients. The mean patient age was 43 years (SD 18.5), and 59.3% of the patients
      were female. Regarding the diagnosis, the most frequents ones where: ANCA
      associated vasculitis followed by systemic lupus erythematosus and catastrophic
      antiphospholipid syndrome. The average number of sessions per patient was 5 (SD
      1.8), and the average plasma exchange per patient was 1.3 plasma volume
      replacement units. The most used replacement solution was frozen fresh plasma
      (FFP; 63.2% of the sessions). Of all the sessions, 4.4% presented complications,
      and the majority of the complications were related to vascular access. Fifteen
      patients required renal replacement therapy (RRT) secondary to the same cause
      that created the need for TPE, 3 patients required RRT due to causes other than
      the TPE diagnostic intervention and 1 patient had undergone chronic dialysis.
      CONCLUSIONS: TPE is a therapeutic alternative that is needed for the management
      of patients with rheumatic diseases with renal involvement and those who are
      refractory to conventional management. Our clinical results were in agreement
      with the global literature.

PMID- 29037312
TI  - Rheumatoid arthritis seems to have DMARD treatment decision influenced by
      fibromyalgia.
AB  - OBJECTIVE: To compare DMARD use in patients with and without FM over time,
      including overtreatment and undertreatment rates in both groups. METHODS: A
      prospective cohort study with patients attending an RA outpatient clinic was
      conducted. Participants were consecutively recruited between March 2006 and June
      2007 and were followed through December 2013. Data on DMARD use (prevalences,
      doses and escalation rates), DAS28, HAQ and radiographic progression were
      compared among RA patients with FM and without FM. Mistreatment clinical
      scenarios were allegedly identified and compared between groups. RESULTS: 256 RA
      patients (32 with FM) were followed for 6.2+/-2.0 (mean+/-SD) years comprising
      2986 visits. At baseline, RA duration was 11.1+/-7.4 years. DAS28 and HAQ were
      greater in RA with FM group, and were closer to RA without FM group towards the
      end. RA patients with FM used higher doses of tricyclic antidepressants,
      leflunomide and prednisone, and lower doses of methotrexate. When compared to RA
      patients without FM, participants with RA and FM used more often tricyclic
      antidepressants, leflunomide, prednisone, continuous analgesics and less often
      methotrexate. Groups presented similar 7-year biologic-free survival, and
      radiographic progression-free survival in Cox regression. RA patients with FM had
      greater proportions of visits in mistreatment scenarios when compared to RA
      patients without FM (28.4 vs. 19.8%, p<0.001). CONCLUSIONS: RA patients with FM
      used more leflunomide and prednisone, and RA mistreatment was more frequent in FM
      patients. Certainly, RA patients with FM will benefit from a personalized T2T
      strategy, including ultrasound (when suitable) and proper FM treatment.

PMID- 29037313
TI  - Prevalence of ischemic heart disease and associated factors in patients with
      rheumatoid arthritis in Southern Brazil.
AB  - OBJECTIVE: To estimate the prevalence of ischemic heart disease and associated
      factors in patients with rheumatoid arthritis. METHODS: A cross-sectional study
      using the American College of Rheumatology diagnostic criteria in order to select
      patients seen at primary or secondary health care units in Blumenau, Santa
      Catarina, Southern Brazil, in 2014. The presence of ischemic heart disease was
      defined as an acute myocardial infarction with percutaneous coronary intervention
      or coronary artery bypass graft surgery that has occurred after diagnosis.
      Fischer's exact test, Wald's linear trend test, and multivariate logistic
      regression analysis were used to test the associations. RESULTS: Among 296
      patients (83.1% female) with a mean age of 56.6 years and a mean rheumatoid
      arthritis duration of 11.3 years, 13 reported having acute myocardial infarction
      requiring a percutaneous or surgical reperfusion procedure, a prevalence of 4.4%
      (95% CI 2.0-6.7). Diabetes Mellitus (odds ratio [OR] 4.9 [95% CI 1.6-13.8]) and
      disease duration >10 years (OR 8.2 [95% CI 1.8-39.7]) were the only factors
      associated with an ischemic disease that remained in the final model, after the
      multivariate analysis. CONCLUSION: The prevalence of acute myocardial infarction
      was similar to that observed in other studies. Among the traditional risk
      factors, Diabetes Mellitus, and among the factors related to rheumatoid
      arthritis, disease duration, were the variables associated with comorbidity.

PMID- 29037314
TI  - Pulmonary magnetic resonance imaging is similar to chest tomography in detecting
      inflammation in patients with systemic sclerosis.
AB  - Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are
      prevalent complications of systemic sclerosis (SSc) and are currently the leading
      causes of death related to the disease. The accurate recognition of these
      conditions is therefore of utmost importance for patient management. A study was
      carried out with 24 SSc patients being followed at the Rheumatology Department of
      the Hospital de Clinicas of Universidade Federal do Parana (UFPR) and 14 healthy
      volunteers, with the objective of evaluating the usefulness of lung magnetic
      resonance imaging (MRI) when assessing ILD in SS patients. The results obtained
      with lung MRI were compared to those obtained by computed tomography (CT) of the
      chest, currently considered the examination of choice when investigating ILD in
      SS patients. The assessed population was predominantly composed of women with a
      mean age of 50 years, limited cutaneous SS, and a disease duration of
      approximately 7 years. In most cases, there was agreement between the findings on
      chest CT and lung MRI. Considering it is a radiation-free examination and capable
      of accurately identifying areas of lung tissue inflammatory involvement, lung MRI
      showed to be a useful examination, and further studies are needed to assess
      whether there is an advantage in using lung MRI instead of chest CT when
      assessing ILD activity in SS patients.

PMID- 29037315
TI  - Prevalence of fibromyalgia in patients treated at the bariatric surgery
      outpatient clinic of Hospital de Clinicas do Parana - Curitiba.
AB  - INTRODUCTION: Fibromyalgia (FM) is a chronic pain syndrome characterized by
      generalized pain. It is known that obese patients have more skeletal muscle pain
      and physical dysfunction than normal weight patients. Therefore, it is important
      that the early diagnosis of FM be attained in obese patients. OBJECTIVE: To
      determine the prevalence of FM in a group of obese patients with indication of
      bariatric surgery. MATERIALS AND METHODS: The patients were recruited from the
      Bariatric Surgery outpatient clinic of Hospital de Clinicas of UFPR (HC-UFPR)
      before being submitted to surgery. Patient assessment consisted in verifying the
      presence or absence of FM using the 1990 and 2011 ACR criteria, as well as the
      presence of comorbidities. RESULTS: 98 patients were evaluated, of which 84 were
      females. The mean age was 42.07 years and the BMI was 45.39. The prevalence of FM
      was 34% (n=29) according to the 1990 criteria and 45% (n=38) according to the
      2011 criteria. There was no difference in age, BMI, Epworth score and prevalence
      of other diseases among patients who met or not the 1990 criteria. Only
      depression was more common in patients with FM. (24.14% vs. 5.45%). The same
      findings were seen in patients that met the 2011 criteria. CONCLUSIONS: The
      prevalence of FM in patients with morbid obesity is extremely high. However, BMI
      does not differ in patients with or without FM. The presence of depression may be
      a risk factor for the development of FM in these patients.

PMID- 29037316
TI  - Intestinal parasites infection: protective effect in rheumatoid arthritis?
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, with a
      progressive course, characterized by chronic synovitis that may evolve with
      deformities and functional disability, and whose early treatment minimizes joint
      damage. Its etiopathogenesis is not fully elucidated but comprises immunologic
      responses mediated by T helper cells (Th1). An apparent minor severity of RA in
      patients from regions with lower income could be associated with a higher
      prevalence of gut parasites, especially helminths. Strictly, a shift in the
      immune response toward the predominance of T helper cells (Th2), due to the
      chronic exposure to helminths, could modulate negatively the inflammation in RA
      patients, resulting in lower severity/joint injury. The interaction between the
      immunological responses of parasitic helminths in rheumatoid arthritis patients
      is the purpose of this paper.

PMID- 29037318
TI  - Coexistence of hypertrophic osteoarthropathy and myelofibrosis.

PMID- 29037317
TI  - Effect of vitamin D supplementation on patients with systemic lupus
      erythematosus: a systematic review.
AB  - The objective of this systematic review was to analyze clinical trials carried
      out for the investigation of the effect of vitamin D supplementation on systemic
      lupus erythematosus. The research was performed from August to September 2016,
      without limits regarding year of publication, restriction of gender, age, and
      ethnicity. For the guiding question, the PICO strategy was employed. To evaluate
      the quality of the publications the PRISMA protocol and Jadad scale were used.
      The risk of bias analysis of the clinical trials was performed using the Cochrane
      collaboration tool. After the process of article selection and removal of
      duplicates, four articles were identified as eligible. The results of three
      studies showed a positive effect of supplementation on disease activity reduction
      and significant improvement in levels of inflammatory markers, fatigue, and
      endothelial function. Only one study showed no improvement in disease activity
      after supplementation. Moreover, all studies showed an increase in serum vitamin
      D levels. The data from this review provide evidence on the benefits of vitamin D
      supplementation in patients with lupus and vitamin D insufficiency/deficiency.
      However, it is still necessary to elucidate whether vitamin D acts in the
      protection against this metabolic disorder, as well as the standardization of the
      type, dose and time of vitamin D supplementation.

PMID- 29037319
TI  - Devic's disease in an adolescent girl with juvenile dermatomyositis.

PMID- 29037320
TI  - Disseminated histoplamosis in adolescent mimicking granulomatosis with
      polyangiitis.

PMID- 29037321
TI  - Whipple's disease manifested as difficult-to-diagnose polyarthralgia: a case
      report and literature review.

PMID- 29037322
TI  - Improvement of nailfold capillary microangiopathy after immunosuppressant therapy
      in a child with clinically amyopathic juvenile dermatomyositis.

PMID- 29037323
TI  - Rheumatoid arthritis in elderly and young patients.

PMID- 29037324
TI  - Back pain and behavioral habits of high school students: a comparative study of
      two Brazil's regions.

PMID- 29037325
TI  - Erratum to "Effects of the use of growth hormone in children, adolescents with
      juvenile idiopathic arthritis: a systematic review" (Rev Bras Reumatol.
      2017;57(2):100-106).

PMID- 29037326
TI  - beta-hydroxy-beta-methylbutyrate free acid supplementation may improve recovery
      and muscle adaptations after resistance training: a systematic review.
AB  - beta-Hydroxy-beta-methylbutyrate free acid (HMB-FA) has been suggested to
      accelerate the regenerative capacity of skeletal muscle after high-intensity
      exercise and attenuate markers of skeletal muscle damage. Herein a systematic
      review on the use of HMB-FA supplementation as an ergogenic aid to improve
      measures of muscle recovery, performance, and hypertrophy after resistance
      training was conducted. This review was performed using the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses. We included randomized, double
      blinded, placebo-controlled trials investigating the effects of HMB-FA
      supplementation in conjunction with resistance exercise in humans. The search was
      conducted using Medline and Google Scholar databases for the terms beta-hydroxy
      beta-methylbutyrate, HMB free acid, exercise, resistance exercise, strength
      training, and HMB supplementation. Only research articles published from 1996 to
      2016 in English language were considered for the analysis. Nine studies met the
      criteria for inclusion in the analyses. Most studies included resistance-trained
      men, and the primary intervention strategy involved administration of 3g of HMB
      FA per day. In conjunction with resistance training, HMB-FA supplementation may
      attenuate markers of muscle damage, augment acute immune and endocrine responses,
      and enhance training-induced muscle mass and strength. HMB-FA supplementation may
      also improve markers of aerobic fitness when combined with high-intensity
      interval training. Nevertheless, more studies are needed to determine the overall
      efficacy of HMB-FA supplementation as an ergogenic aid.

PMID- 29037327
TI  - Low dietary intake of n-3 fatty acids, niacin, folate, and vitamin C in Korean
      patients with schizophrenia and the development of dietary guidelines for
      schizophrenia.
AB  - Inappropriate dietary intake and poor nutritional status are reported to be
      associated with metabolic syndrome and psychopathology in patients with
      schizophrenia. We hypothesized that inappropriate dietary habits and insufficient
      dietary intake of specific nutrients are associated with schizophrenia. To test
      the hypothesis, we assessed the dietary habits and nutritional intake of patients
      with schizophrenia and then developed suitable dietary guidelines. In total, 140
      subjects (73 controls and 67 patients with schizophrenia from community mental
      health centers) were included, and dietary intakes were analyzed using a semi
      quantitative food frequency questionnaire. As a result, the proportion of
      overweight or obese patients was significantly higher in schizophrenia subjects
      (64.2%) compared with control subjects (39.7%) (P=.004). The male schizophrenia
      patients had significantly lower dietary intakes of protein, polyunsaturated
      fatty acids (PUFAs), vitamin K, niacin, folate, and vitamin C than the male
      control subjects. In all multiple logistic regression models, subjects with the
      "low" dietary intake of protein, n-3 PUFAs, niacin, folate, and vitamin C had a
      significantly higher odds ratios for schizophrenia compared with those with the
      "high" dietary intake category of each nutrient. Therefore, maintenance of a
      healthy body weight and sufficient dietary intake of protein, PUFAs, niacin,
      folate, and vitamin C are recommended for Korean patients with schizophrenia.

PMID- 29037328
TI  - Xyloglucan intake attenuates myocardial injury by inhibiting apoptosis and
      improving energy metabolism in a rat model of myocardial infarction.
AB  - The development of coronary heart disease can be divided into preocclusion and
      postocclusion steps. We previously showed that cell wall polysaccharides
      consisting of a high content of arabinose and/or xylose, such as apple pectin,
      protected against myocardial injury by inhibiting postocclusion steps. We
      hypothesized that xyloglucan, another apple cell wall polysaccharide that
      consists of a high content of xylose, might also show myocardial protection. To
      test the hypothesis, rats were supplemented with either tamarind xyloglucan (TXG)
      (1, 10, and 100 mg/kg per day) or cotton cellulose (CCL) (100mg/kg per day) for 3
      days. Then, rats underwent 30 minutes of ischemia followed by 3 hours of
      reperfusion. Supplementation with TXG at a dosage greater than 10mg/kg per day
      significantly reduced the infarct size (IS), whereas supplementation with CCL at
      100mg/kg per day did not reduce IS. TXG supplementation up-regulated the
      expression of myoglobin and fatty acid-binding protein, both of which are known
      to be involved in apoptosis and ATP generation. Indeed, TXG supplementation
      inhibited apoptosis through decrease in p38 and JNK phosphorylation, increase in
      Bcl-2/Bax ratio, inhibition in the conversion of procaspase-3 to cleaved caspase
      3, and decrease in the generation of DNA nicks. From these results, we
      demonstrated that xyloglucan in apple can protect against myocardial injury by
      inhibiting apoptosis and improving energy metabolism. Therefore, apple xyloglucan
      and pectin contribute to the known beneficial effects of apple in reducing the
      risk of coronary heart disease by blocking postocclusion steps through apoptosis
      inhibition. In addition, this study demonstrates the feasibility of developing
      TXG as a cardioprotectant.

PMID- 29037330
TI  - Waist circumference shows the highest predictive value for metabolic syndrome,
      and waist-to-hip ratio for its components, in Spanish adolescents.
AB  - Both waist circumference (WC) and waist-to-hip ratio (WHR) have been proposed as
      predictors of metabolic syndrome (MetS) in adolescents, but no consensus has been
      reached to date. This study hypothesizes that WC provides a greater predictive
      value for MetS in Spanish adolescents than WHR. A cross-sectional study was
      performed on 1001 adolescents (13.2 +/- 1.2 years) randomly recruited from
      schools in southeast Spain. Anthropometric measures were correlated with the
      components of MetS (triglycerides, glucose, blood pressure, and high-density
      lipoprotein cholesterol) as well as inflammation markers (interleukin-6 and tumor
      necrosis factor-alpha , C-reactive protein, and ceruloplasmin). Receiver-operator
      curves were created to determine the predictive value of these variables for
      MetS. Boys had higher values of all anthropometric parameters compared with
      girls, but the prevalence of MetS was significantly higher in girls. WHR was the
      only parameter that correlated significantly with all biochemical and
      inflammatory variables in boys. In girls, WHR, body mass index, waist-to-height
      ratio, WC, and body fat percentage correlated only with plasma insulin levels,
      systolic and diastolic pressures, and ceruloplasmin. In both groups, all
      anthropometric measures were able to predict MetS (area under the curve > 0.94).
      In particular, WC was able to predict MetS with area under the curve = 1.00.
      However, WHR was able to predict a higher number of components of MetS. WHR was
      the anthropometric index that showed the highest predictive value for MetS
      components, whereas WC was the one that best predicted the MetS among the
      population of adolescents studied. These findings justify the need to incorporate
      WHR and WC determinations into daily clinical practice to predict the MetS.

PMID- 29037329
TI  - Smokers report lower intake of key nutrients than nonsmokers, yet both fall short
      of meeting recommended intakes.
AB  - Smoking is a major risk factor in the development of preventable disease which
      may be due to a poorer diet and the reduced nutrient intake of smokers. Our
      objective was to compare and evaluate the reported intake of current smokers with
      that of nonsmokers among participants of a study evaluating stress and smoking.
      We hypothesized (1) that overall energy and nutrient intake would be reduced in
      smokers compared with nonsmokers and (2) that smokers would have increased
      noncompliance with Dietary Reference Intakes (DRIs). Men and women (smokers
      n=138, nonsmokers n=46) completed a 3-day diet record at baseline. Mean energy
      and nutrient intakes were stratified by smoking status and compared with DRI
      levels. The mean body mass index was 28.3+/-0.5kg/m2 for smokers and 27.2+/
      1.0kg/m2 for nonsmokers. Compared with nonsmokers, the smokers reported lower
      intakes of energy, total polyunsaturated fatty acids, linolenic acid,
      docosahexaenoic acid, total sugars, calcium, iron, magnesium, phosphorus,
      potassium, vitamin C, riboflavin, niacin, pantothenic acid, vitamin B6, folate,
      vitamin A, and vitamin E. Smokers reported reduced compliance with the DRIs for
      iron, phosphorus, vitamin C, riboflavin, and folate compared with nonsmokers.
      Unlike other evaluations of smokers vs nonsmokers, we observed no difference in
      body weight between groups. Smokers and nonsmokers alike reported dietary intakes
      lower than the DRIs for many nutrients. However, the reported nutrient intake of
      the smokers was substantially lower than nonsmokers for key nutrients, and they
      were more likely to not comply with the DRIs for essential nutrients, placing
      them at increased risk of chronic disease.

PMID- 29037331
TI  - Preload of slowly digestible carbohydrate microspheres decreases gastric emptying
      rate of subsequent meal in humans.
AB  - Gastric emptying rate influences how fast the nutrients of a meal are delivered
      to the body, and when slow, it moderates glycemic response and may impact
      satiety. Carbohydrates are one of the macronutrients that trigger the ileal
      brake, and we hypothesized that slowly digestible carbohydrate (SDC) administered
      in a premeal load would delay gastric emptying. A crossover design study was
      conducted with 10 healthy adults using fabricated SDC-microspheres (cooked) that
      were given 20 minutes before a non-nutritive viscous paste meal. There were 4
      treatment arms, each separated by a 1-week washout period, consisting of (1) the
      paste alone, (2) a rapidly digesting maltodextrin (Polycose) preload followed by
      the paste 20 minutes later, (3) an SDC-microsphere preload followed by the paste,
      and (4) a comparably slower SDC-microsphere preload followed by the paste. A 13C
      labeled octanoic acid breath test method was used to measure gastric emptying,
      with the label incorporated into the non-nutritive paste. The microspheres were
      less than 1 mm in diameter (a size that does not require breakdown in the stomach
      before emptying) and, after cooking, were of the same density value. Compared
      with the paste alone, both of the SDC-microsphere preloads (slow and comparably
      slower digesting) decreased gastric emptying rate of the paste, with the latter
      having the most effect (half-emptying times of 1.7, 2.3, and 2.8 hours,
      respectively [each different at P<.05]). In conclusion, SDCs decreased gastric
      emptying rate, and this was suggested to be due to a triggering of the ileal
      brake.

PMID- 29037332
TI  - Dihydrosterculic acid from cottonseed oil suppresses desaturase activity and
      improves liver metabolomic profiles of high-fat-fed mice.
AB  - Polyunsaturated fatty acid (PUFA)-rich diets are thought to provide beneficial
      effects toward metabolic health in part through their bioactive properties. We
      hypothesized that increasing PUFA intake in mice would increase peroxisome
      proliferator activated receptor delta (PPARdelta) expression and activity, and we
      sought to examine the effect of different PUFA-enriched oils on muscle PPARdelta
      expression. One of the oils we tested was cottonseed oil (CSO) which is primarily
      linoleic acid (53%) and palmitic acid (24%). Mice fed a CSO-enriched diet (50%
      energy from fat) displayed no change in muscle PPARdelta expression; however, in
      the liver, it was consistently elevated along with its transcriptional
      coactivator Pgc-1. Male mice were fed chow or CSO-, saturated fat (SFA)-, or
      linoleic acid (18:2)-enriched diets that were matched for macronutrient content
      for 4 weeks. There were no differences in food intake, body weight, fasting
      glucose, glucose tolerance, or energy expenditure between chow- and CSO-fed mice,
      whereas SFA-fed mice had increased fat mass and 18:2-fed mice were less glucose
      tolerant. Metabolomic analyses revealed that the livers of CSO-fed mice closely
      matched those of chow-fed but significantly differed from SFA- and 18:2-enriched
      groups. Fatty acid composition of the diets and livers revealed an impairment in
      desaturase activity and the presence of dihydrosterculic acid (DHSA) in the CSO
      fed mice. The effect of DHSA on PPARdelta and stearoyl-CoA desaturase-1
      expression mimicked that of the CSO-fed mice. Taken together, these data suggest
      that DHSA from CSO may be an effective means to increase PPARdelta expression
      with concomitant suppression of liver stearoyl-CoA desaturase-1 activity.

PMID- 29037333
TI  - [Towards a validation of the hybrid neuropsychiatric territory].

PMID- 29037334
TI  - An International Curriculum for Neuropsychiatry and Behavioural Neurology.
AB  - With major advances in neuroscience in the last three decades, there is an
      emphasis on understanding disturbances in thought, behaviour and emotion in terms
      of their neuroscientific underpinnings. While psychiatry and neurology, both of
      which deal with brain diseases, have a historical standing as distinct
      disciplines, there has been an increasing need to have a combined
      neuropsychiatric approach to deal with many conditions and disorders.
      Additionally, there is a body of disorders and conditions that warrants the
      skills sets and knowledge bases of both disciplines. This is the territory
      covered by the subspecialty of Neuropsychiatry from a 'mental' health perspective
      and Behavioural Neurology from a 'brain' health perspective. This paper
      elaborates the neuropsychiatric approach to dealing with brain diseases, but also
      argues for the delineation of a neuropsychiatric territory. In the process, it
      describes a curriculum for the training of a neuropsychiatrist or a behavioural
      neurologist who is competent in providing a unified approach to the diagnosis and
      management of this set of conditions and disorders. The paper describes in some
      detail the objectives of training in neuropsychiatry and the key competencies
      that should be achieved in such higher training after a foundational training in
      psychiatry and neurology. While aiming for an internationally relevant training
      program, the paper acknowledges the local and regional differences in training
      expertise and requirements. It provides a common framework of training for both
      Neuropsychiatry and Behavioural Neurology, while accepting the differences in
      skills and emphasis that basic training in psychiatry or neurology will bring to
      the subspecialty training. The future of Neuropsychiatry (or Behavioural
      Neurology) as a discipline will be influenced by the successful adoption of such
      a unified training curriculum.

PMID- 29037335
TI  - [Catatonia and Delirium: Syndromes that may Converge in the Neuropsychiatric
      Patient].
AB  - INTRODUCTION: Catatonia and delirium are two different and independent syndromes.
      Catatonia is a psychomotor syndrome associated with a variety of diseases of
      different medical causes and is characterised by lack of activity, induction of
      passive postures against gravity, opposition or absence of response to external
      stimuli, waxy flexibility, stereotypies, mannerisms and echophenomena. Delirium
      is characterised by consciousness and cognitive alterations, mainly attention and
      orientation and usually of acute onset, which tend to fluctuate during the day
      and with evidence that the alteration is a direct physiological consequence of a
      disease, intoxication or substance withdrawal. Despite the differences and the
      fact that the classifications exclude the possibility that these syndromes may
      manifest together, several case reports and studies in groups of patients have
      postulated that the two conditions can occur together. MATERIAL AND METHODS: In
      this study we identified 16 hospitalised patients who experienced both syndromes
      at the same time as confirmed by the Delirium Rating Scale-Revised (DRS-98) and
      the Bush-Francis Catatonia Rating Scale (BFCRS). RESULTS: Patient outcome was
      followed during hospitalisation and the patients' clinical condition upon
      discharge. These patients had mostly neurological diagnoses, long hospital stays,
      required treatment with antipsychotics and benzodiazepines and had frequent
      complications. CONCLUSIONS: Catatonia and delirium are syndromes that can present
      at the same time, resulting in worse patient outcome and an increased risk of
      complications.

PMID- 29037336
TI  - Neuropsychiatry: Towards a Philosophy of Praxis.
AB  - Neuropsychiatry is a specialized clinical, academic and scientific discipline
      with its field located in the borderland territory between neurology and
      psychiatry. In this article, we approach the theoretical definition of
      neuropsychiatry, and in order to address the practical aspects of the discipline,
      we describe the profile of a neuropsychiatric liaison service in the setting of a
      large hospital for neurological diseases in a middle-income country. An audit of
      consecutive in-patients requiring neuropsychiatric assessment at the National
      Institute of Neurology and Neurosurgery of Mexico is reported, comprising a total
      of 1212 patients. The main neurological diagnoses were brain infections (21%),
      brain neoplasms (17%), cerebrovascular disease (14%), epilepsy (8%), white matter
      diseases (5%), peripheral neuropathies (5%), extrapyramidal diseases (4%), ataxia
      (2%), and traumatic brain injury and related phenomena (1.8%). The most frequent
      neuropsychiatric diagnoses were delirium (36%), depressive disorders (16.4%),
      dementia (14%), anxiety disorders (8%), frontal syndromes (5%), adjustment
      disorders (4%), psychosis (3%), somatoform disorders (3%), and catatonia (3%).
      The borderland between neurology and psychiatry is a large territory that
      requires the knowledge and clinical skills of both disciplines, but also the
      unique expertise acquired in a clinical and academic neuropsychiatry program.

PMID- 29037337
TI  - [Social Cognition and its Contribution to the Rehabilitation of Behavioural
      Disorders in Traumatic Brain Injury].
AB  - Social behaviour disorders in traumatic brain injury are caused by the
      dysfunction of cognitive processes involved in social and interpersonal
      interaction. The concept of social cognition was introduced by authors studying
      schizophrenia, autism or mental retardation. The boundaries and the content of
      the concept have not yet been definitively defined, but theory of mind, empathy
      and emotional processing are included in all the models proposed. The strategies
      proposed to improve social behaviour focus on the restoration of cognitive
      processes such as working memory, emotional recognition and processing, and
      empathy, as well as social skills. To date, there is very little evidence on the
      efficacy of the aforementioned social cognition strategies.

PMID- 29037338
TI  - [The Many Faces of Orbitofrontal Syndrome].
AB  - Orbitofrontal syndrome is a neuropsychiatric syndrome composed of cognitive,
      affective and behavioural symptoms, disrupting some of the traits that define us
      as a species, like cognitive flexibility and affective regulation. In order to
      effectively treat the condition, the clinician needs to be familiar with both the
      functional neuroanatomy and the neuropsychiatric semiology of the syndrome. A
      review of the literature is presented, emphasising the broad spectrum of clinical
      manifestations of the syndrome, together with three clinical vignettes showing
      the many faces of the syndrome. Several factors influencing the heterogeneity of
      clinical presentation are discussed. Taking a hierarchical model of neural
      networks, two core concepts, loss of interoceptive/exteroceptive integration and
      loss of affective regulation, are proposed in looking for invariants in
      orbitofrontal syndrome.

PMID- 29037339
TI  - [Beyond Cognitive Impairment: Neuropsychiatric Symptoms in Neurodegenerative
      Dementias].
AB  - As life expectancy increases, the number of people diagnosed with
      neurodegenerative dementia also increases. Although cognitive impairment is
      central in dementia, neuropsychiatric symptoms (NPS) are very important because
      they increase both direct and indirect costs by generating greater morbidity,
      caregiver distress, use of medication and institutionalisation. Furthermore, it
      is important to understand the nature of NPS, since they can vary across the
      different types of dementia and may provide useful clinical information regarding
      the aetiology of cognitive impairment. The first-line management of NPS in
      dementia is non-pharmacological; internal and external causes should first be
      identified and strategies developed to modify the behavioural patterns of the
      patient and their caregiver. In addition, changes in the patient's surroundings
      that may improve patient performance and behaviour should be encouraged. If these
      practices are not satisfactory, a pharmacological treatment approach is adopted
      that includes anti-dementia drugs, antipsychotics, antidepressants, mood
      stabilisers and benzodiazepines. However, psychoactive drugs do not offer
      sufficient efficacy and most of them have significant adverse effects, so each
      patient should be individually assessed, together with the implementation of non
      pharmacological strategies, before deciding on pharmacological treatment for the
      management of NPS in dementia.

PMID- 29037340
TI  - [Neuropsychiatry Of Movement Disorders].
AB  - Movement disorders can be defined as neurological syndromes presenting with
      excessive or diminished automatic or voluntary movements not related to weakness
      or spasticity. Both Parkinson's disease (PD) and Huntington's disease (HD) are
      well-known examples of these syndromes. The high prevalence of comorbid
      psychiatric symptoms like depression, anxiety, obsessive-compulsive symptoms,
      hallucinations, delusions, impulsivity, sleep disorders, apathy and cognitive
      impairment mean that these conditions must be regarded as neuropsychiatric
      diseases. In this article, we review neuroanatomical (structural and functional),
      psychopathological and neuropsychological aspects of PD and HD. The role of
      fronto-subcortical loops in non-motor functions is particularly emphasised in
      order to understand the clinical spectrum of both diseases, together with the
      influence of genetic, psychological and psychosocial aspects. A brief description
      of the main psychopharmacological approaches for both diseases is also included.

PMID- 29037341
TI  - [Neurosyphilis: an Age-old Problem that is Still Relevant Today].
AB  - Neurosyphilis is the clinical manifestation of syphilis that can arise during
      either the early or late stages of infection. Even though dedicated treatment for
      all clinical forms of syphilis has been available for many years, the advanced
      stages of the disease are still prevalent, with irreversible sequelae. This
      article reviews the current evidence, diagnostic methods and specific treatment
      for tertiary syphilis.

PMID- 29037342
TI  - [Pharmacological Treatment of Apathy in Parkinson's Disease: a Systematic Review
      of the Literature].
AB  - INTRODUCTION AND OBJECTIVES: Apathy, defined as a deficit for initiating and
      maintaining action, is a symptom affecting patients with diverse psychiatric and
      neuropsychiatric diseases, including dementia, sequelae of traumatic brain
      injury, schizophrenia, depression, and Parkinson's disease (PD). Apathy
      negatively affects function and quality of life of PD patients, and it is an
      important cause of caregiver's distress. The pharmacological treatment of apathy
      in PD is the focus of this systematic review. METHODS: A comprehensive search and
      systematic selection was performed in different databases of original research
      papers on the treatment of apathy in PD. The results were then consolidated, and
      a critical analysis was made of the research papers. The results are then
      discussed according to the methodological standards for systematic reviews of the
      literature. RESULTS: A total of 11 studies were included. Although some studies
      showed efficacy, all of them had important methodological limitations that
      hampered the interpretation of results. The results of the examined studies
      cannot be considered as evidence for guiding clinical decisions. CONCLUSIONS: So
      far, no evidence-based recommendations can be offered for the treatment of apathy
      in PD. More studies with better methodological quality are needed. It is a
      potentially fruitful area for research and one badly needed by both PD patients
      and their caregivers.

PMID- 29037343
TI  - The prevalence of selected major birth defects in the United States.
AB  - Although collectively they are fairly common, birth defects receive limited
      attention as a group of outcomes either clinically or from a public health
      perspective. This article provides an overview of the prevalence, trends and
      selected socio-demographic risk factors for several major birth defects,
      including neural tube defects, cranio-facial anomalies, congenital heart defects,
      trisomies 13, 18, and 21, and gastroschisis and omphalocele. Attention should
      focus on strengthening existing registries, creating birth defects surveillance
      programs in states that do not have them, and standardizing registry methods so
      that broadly national data to monitor these trends are available.

PMID- 29037344
TI  - Optimism, enthusiasm, responsibility.

PMID- 29037345
TI  - Factors influencing the hemodynamic response to balloon angioplasty in the
      treatment of outflow anomalies of internal jugular veins.
AB  - OBJECTIVE: Percutaneous transluminal angioplasty (PTA) of the internal jugular
      veins (IJVs) has been proposed in recent years to treat chronic cerebrovascular
      venous insufficiency, with discordant results. Moreover, very little is known
      about the efficacy of PTA in restoring a normal cerebral venous outflow. The aim
      of this study was to investigate the anatomic factors and patient characteristics
      that might influence the efficacy of PTA of the IJV. METHODS: There were 797
      consecutive patients with venous outflow anomalies who underwent standardized,
      operator-independent catheter venography and PTA of the IJVs. Before and after
      PTA, morphologic and hemodynamic anomalies of the IJVs were documented. The
      primary end point of the study was to evaluate the morphologic factors
      influencing the efficacy of angioplasty in improving IJV outflow. RESULTS: PTA
      resulted in an increased outflow through the IJVs in most patients. However,
      younger individuals with transverse endoluminal defects and higher pre-PTA flows
      are more likely to respond well to PTA compared with those who exhibit
      hypoplasia, stenosis, or longitudinal endoluminal defects. CONCLUSIONS: This
      study identified the factors that influence and could predict the efficacy of PTA
      in the treatment of IJV anomalies.

PMID- 29037346
TI  - Contemporary outcomes of elective iliocaval and infrainguinal venous intervention
      for post-thrombotic chronic venous occlusive disease.
AB  - BACKGROUND: Patients with iliofemoral deep venous thrombosis are at risk for
      development of post-thrombotic syndrome. Iliac vein stenting has been shown to
      significantly improve clinical outcomes in patients with venous outflow
      obstruction, although many studies include a heterogeneous population with
      several different venous pathologic processes. Our objective was to evaluate the
      results of iliocaval and infrainguinal venous intervention for venous outflow
      obstruction due to post-thrombotic chronic venous occlusive disease. METHODS: All
      patients treated at a single institution for symptomatic iliocaval venous
      occlusive lesions with and without infrainguinal extension between 2008 and 2015
      were retrospectively analyzed. Nonthrombotic iliac vein lesions were excluded
      from analysis. All patients with symptomatic post-thrombotic occlusion of the
      iliac vein or inferior vena cava (IVC) and a Clinical, Etiology, Anatomy, and
      Pathophysiology (CEAP) score of 3 or greater were included. Demographics of the
      patients, presence of IVC filters at presentation, presenting CEAP score,
      postintervention CEAP score, primary and secondary patency, wound healing and
      subjective clinical improvement outcomes, and procedural details were recorded in
      a database. RESULTS: There were 105 patients with symptomatic iliocaval venous
      occlusive lesions identified, of which 31 patients (42 limbs) met inclusion
      criteria. Presenting symptoms included pain or swelling (100%); venous
      claudication (81%); and CEAP class 3 (76%), 4 or 5 (14%), or 6 (10%). All
      patients presented with either subacute (>30 days [35%]) or chronic (>90 days
      [65%]) iliocaval venous thrombosis. Procedural technical success with venous
      recanalization was achieved in 100% of cases and in 46% of IVC filter retrieval
      attempts. Overall clinical improvement was achieved in 84% of patients; complete
      clinical resolution was obtained in 42% and a decrease in CEAP score in 65%. At a
      mean follow-up of 14.7 months (range, 2-49 months), primary and secondary 1-year
      patency was 66% and 75% overall, and primary patency was equivalent between
      patients requiring isolated iliac venous stenting and those requiring
      infrainguinal stent extension (68% vs 65%, respectively; P = .74, not
      significant). Patients who presented with IVC filters had a higher rate of
      complete clinical resolution if the filter could be removed (100%) compared with
      those patients in whom the filter could not be removed (17%; P < .01).
      CONCLUSIONS: Treatment of chronic venous occlusive disease with iliocaval and
      infrainguinal venous stenting is associated with acceptable 1-year patency rates,
      healing of venous ulcers, and a significant reduction in symptoms and CEAP score.
      Patients who underwent successful removal of indwelling IVC filters showed
      improved clinical outcomes compared with those in whom the IVC filter could not
      be removed.

PMID- 29037347
TI  - Invited commentary.

PMID- 29037348
TI  - Retrieval characteristics of the Bard Denali and Argon Option inferior vena cava
      filters.
AB  - OBJECTIVE: The purpose of this study was to compare the retrieval characteristics
      of the Option Elite (Argon Medical, Plano, Tex) and Denali (Bard, Tempe, Ariz)
      retrievable inferior vena cava filters (IVCFs), two filters that share a similar
      conical design. METHODS: A single-center, retrospective study reviewed all Option
      and Denali IVCF removals during a 36-month period. Attempted retrievals were
      classified as advanced if the routine "snare and sheath" technique was initially
      unsuccessful despite multiple attempts or an alternative endovascular maneuver or
      access site was used. Patient and filter characteristics were documented.
      RESULTS: In our study, 63 Option and 45 Denali IVCFs were retrieved, with an
      average dwell time of 128.73 and 99.3 days, respectively. Significantly higher
      median fluoroscopy times were experienced in retrieving the Option filter
      compared with the Denali filter (12.18 vs 6.85 minutes; P = .046). Use of
      adjunctive techniques was also higher in comparing the Option filter with the
      Denali filter (19.0% vs 8.7%; P = .079). No significant difference was noted
      between these groups in regard to gender, age, or history of malignant disease.
      CONCLUSIONS: Option IVCF retrieval procedures required significantly longer
      retrieval fluoroscopy time compared with Denali IVCFs. Although procedure time
      was not analyzed in this study, as a surrogate, the increased fluoroscopy time
      may also have an impact on procedural direct costs and throughput.

PMID- 29037349
TI  - The optimal procedure of modified Rex shunt for the treatment of extrahepatic
      portal hypertension in children.
AB  - OBJECTIVE: Since 2008, the modified Rex shunt has been used for the treatment of
      extrahepatic portal venous obstruction (EHPVO) in our center, and satisfactory
      results were initially achieved. However, the postoperative recurrence rate
      gradually increased. We therefore performed a retrospective study to evaluate the
      outcome and identify the optimal procedure. METHODS: Between October 2008 and
      March 2016, 79 children with EHPVO underwent the Rex shunt in our hospital: 48
      underwent the gastroportal shunt (GP), 26 underwent the portal cavernoma-Rex
      shunt with interposition of grafted portal vessel (PP), and 5 underwent a spleen
      preserving splenoportal bypass (SP). The results of these three types of
      operation were compared. RESULTS: The portal pressure and splenic size were
      significantly reduced after surgery (P < .05). The levels of platelet and
      hemoglobin were significantly increased after surgery (P < .05). The operative
      time in the GP group was significantly longer than in the PP group (P = .045).
      The diameter of the bypass vein was significantly larger in the GP group than in
      the PP group (P = .029). Postoperative rebleeding occurred in 19%: 22.9% (11 of
      48) in the GP group, 11.5% (3 of 26) in PP group, and 20% (1 of 5) in the SP
      group. There was no significant difference in the splenic size, postoperative
      portal pressure, hospital stay, blood flow velocity, or hemoglobin among the
      three groups (P > .05). CONCLUSIONS: The modified Rex shunt is an effective
      treatment of EHPVO in children, and we believe that the PP procedure is the most
      suitable modified Rex shunt in our center.

PMID- 29037350
TI  - Prospective study of safety and effectiveness in the use of radiofrequency
      ablation for incompetent great saphenous vein >=12 mm.
AB  - OBJECTIVE: The objective of this study was to assess the outcomes of
      radiofrequency ablation (RFA) in incompetent great saphenous vein (GSV) according
      to its diameter. METHODS: This was a prospective single-center study including
      all patients treated with RFA from September 2014 to December 2015. The sample
      was divided according to the maximum GSV diameter measured on duplex ultrasound
      scan (A, <12 mm; B, >=12 mm). Second-generation catheters (ClosureFast; Covidien,
      Mansfield, Mass) and tumescent anesthesia were used. Clinical stage (according to
      Clinical, Etiology, Anatomy, and Pathophysiology [CEAP] classification), quality
      of life (measured by the 14-item Chronic Venous Insufficiency Questionnaire), and
      pain on visual analog scale were recorded before the procedure and during follow
      up. Technical success was defined as GSV occlusion on duplex ultrasound scan.
      Safety was defined as incidence and type of adverse events at 10 days, 1 month, 6
      months, and 12 months. RESULTS: There were 257 patients included, 183 (71%) with
      GSV diameter <12 mm and 74 (29%) with GSV diameter >=12 mm. Mean GSV diameter was
      8 +/- 2 mm (4-11 mm) and 14 +/- 2 mm (12-21 mm), respectively. Before the
      procedure, although a tendency toward greater clinical severity was observed in
      group B, no significant differences were found in the percentage of patients in
      C4 and C5 categories (A, 10%; B, 22%), median pain perception (A, 40; B, 39), or
      median quality of life value on the 14-item Chronic Venous Insufficiency
      Questionnaire scale (A, 27; B, 27). The rate of GSV occlusion at 1 month (n =
      221) was 97% in group A and 100% in group B (P = .325); at 6 months (n = 158), it
      was 97% and 98%, respectively (P > .999); and at 12 months (n = 90), it was 99%
      and 96% (P = .481). There was a significant improvement in pain and quality of
      life in both groups, without differences between them. Finally, no differences
      between groups were found in terms of adverse events. Paresthesias were the most
      frequent event (A, 4%; B, 5%; P = NS), which disappeared during follow-up in half
      of the cases. Regarding major adverse events, there was only one case of deep
      venous thrombosis in group B. CONCLUSIONS: RFA is safe and effective for the
      treatment of GSV >=12 mm at midterm.

PMID- 29037352
TI  - Invited commentary.

PMID- 29037351
TI  - Rivaroxaban versus fondaparinux for thromboprophylaxis after endovenous laser
      ablation.
AB  - OBJECTIVE: Endovenous heat-induced thrombosis (EHIT) and deep venous thrombosis
      (DVT) are well-known complications after superficial endovenous thermoablation.
      We investigated the efficacy of rivaroxaban in preventing EHIT and DVT after
      endovenous laser ablation (EVLA). METHODS: We retrospectively analyzed a
      consecutive series of patients presenting with truncal varicosis class C2 to C6
      undergoing EVLA. After EVLA, all patients received oral rivaroxaban (10 mg) or
      subcutaneous fondaparinux (2.5 mg) once daily for 3 consecutive days. The primary
      end point was the composite of EHIT or DVT assessed by duplex ultrasound imaging
      after 1 and 4 weeks. EHIT class 1 was defined as the thrombus extending to the
      saphenofemoral junction. Extension into the deep venous system with a cross
      sectional area obstruction <50% was considered EHIT class 2. EHIT class 3 was
      defined as >50% cross-sectional area obstruction. EHIT class 4 was total
      occlusion of the femoral vein. The secondary end points were minor or major
      bleeding, paresthesia, and skin burns. RESULTS: Between February 2009 and
      December 2015, 391 patients (473 limbs) were treated with EVLA of the truncal
      saphenous vein. The primary end point occurred in 13 of 166 (7.8%) and 14 of 225
      (6.2%) after 1 week and in 13 of 166 (7.8%) and 15 of 225 (6.7%) after 4 weeks
      comparing the rivaroxaban and fondaparinux groups (P = .659). EHIT class 1 was
      observed in 20 patients (5.1%) and EHIT class 2 in five (1.3%). No patients had
      EHIT class 3 or 4. The incidence of DVT was one of 166 (0.6%) in the rivaroxaban
      group and two of 225 (0.9%) in the fondaparinux group (P = .750). Minor bleeding
      events occurred in 17 of 166 patients (10.2%) and in 20 of 225 patients (8.9%),
      respectively (P = .652). No major bleeding events were observed. Paresthesia was
      observed in 12.5% in the rivaroxaban group and in 17.8% in the fondaparinux
      group. No skin burns were observed. CONCLUSIONS: Rivaroxaban offers an oral
      medication approach showing no difference in preventing EHIT and DVT compared
      with fondaparinux, without increased bleeding risk.

PMID- 29037353
TI  - Shortened protocol for radiofrequency ablation of perforator veins.
AB  - BACKGROUND: Routine radiofrequency ablation (RFA) of an incompetent perforator
      vein (IPV) using the standard treatment protocol at 85 degrees C has a treatment
      time of 6 minutes. To make treatment time more efficient, we sought to determine
      the effect of a shortened protocol for radiofrequency stylet (RFS) ablation by
      comparing the early success using three different temperatures: 85 degrees C, 90
      degrees C, and 95 degrees C. METHODS: A retrospective study examined 642
      procedures of IPV closures in 255 patients with varying degrees of venous
      insufficiency treated with RFA from 2009 to 2015. The Covidien (Mansfield, Mass)
      RFA system allows the operator to regulate temperature and allows increments in
      temperature of the RFS to 85 degrees C, 90 degrees C, and 95 degrees C. The RFS
      probe was angled at four 90-degree angles at the mentioned temperatures with a
      shorter treatment time at 6, 4, and 3 minutes, respectively. The three different
      treatment protocols were compared. All patients had comparative preoperative and
      postoperative duplex ultrasound scans. Postoperative duplex ultrasound scans were
      performed 3 to 7 days after the procedure. Successful obliteration was defined as
      lack of color flow on postoperative duplex ultrasound scanning. Clinical
      correlation with age, gender, laterality, presenting symptoms (Clinical,
      Etiology, Anatomy, and Pathophysiology [CEAP] classification), location, and vein
      diameter was also performed. RESULTS: Of the 255 patients who underwent RFS
      ablation, 138 were female, with a mean age of 65 years (standard deviation, +/
      14.6 years). These patients had CEAP presentations from C1 to C6 (0 C1, 1 C2, 57
      C3, 118 C4, 4 C5, 75 C6). The location of the 642 IPVs was distributed as 472 in
      the calf and 170 in the ankle; 322 of these procedures were performed on the
      right leg. Use of a shortened protocol had no significant effect on the early
      obliteration rates with the 85 degrees C, 90 degrees C, and 95 degrees C
      protocols, which were 66.1%, 61.8%, and 67.1%, respectively. Significant
      correlation was seen between location of targeted vein and successful
      obliteration (P < .001). There was a borderline inverse linear association
      between higher stylet temperature and successful obliteration in the proximal
      calf at 85 degrees C. After accounting for within-patient correlation, the middle
      and distal calf continued to show higher nonobliteration compared with the ankle.
      No clinical correlation with age, gender, laterality, presenting symptoms of
      CEAP, or vein diameter was observed. CONCLUSIONS: The study showed that
      shortening the protocol time for RFA of the perforator did not make a significant
      difference in the early success rate, regardless of the temperature. The overall
      early success rate is still low (65.1%). RFA of perforator veins has a higher
      successful closure rate in proximal calf and ankle areas compared with the middle
      and distal calf.

PMID- 29037355
TI  - Invited commentary.

PMID- 29037356
TI  - Three-dimensional digital imaging is as accurate and reliable to measure leg
      ulcer area as transparent tracing with digital planimetry.
AB  - OBJECTIVE: An accurate and reliable method for measuring venous leg ulcer (VLU)
      area is important in assessing treatment effects. The new three-dimensional (3D)
      LifeViz digital imaging system (QuantifiCare S.A., Valbonne, France) combines a
      compact, easy to use stereovision camera and image management software to provide
      3D medical images. The aim of this prospective study was to investigate whether
      the 3D LifeViz digital imaging system could be considered a suitable alternative
      to manual transparent wound tracing for the measurement of VLU area and 4-week
      healing rates. METHODS: A prospective cohort study was conducted in two tertiary
      centers between November 2013 and January 2014. The intrarater variability of the
      digital imaging system was assessed by comparison of the target wound (TW) areas
      obtained at the inclusion visit (W0) and 2 days after W0 for each local rater.
      The inter-rater variability of the two methods at W0 and the study end visit was
      assessed using the TW area measurements obtained by local and central raters.
      RESULTS: A total of 36 consecutive outpatients, each presenting with at least one
      VLU and representing a total of 44 TWs, were recruited. At inclusion, comparable
      results were observed with both methods in terms of mean VLU area, showing a good
      correlation of the digital imaging method with the transparent tracing method
      (concordance correlation coefficient [CCC], 0.989; 95% confidence interval [C],
      0.983-0.992). Furthermore, this system detected the same changes in the 4-week
      healing rate as the transparent tracing method, showing that both methods were
      equivalent in measuring changes in VLU areas over time (CCC, 0.996; 95% CI, 0.994
      0.997). Strong intrarater and inter-rater concordances demonstrated good
      reproducibility of the digital imaging system for VLU area measurements (CCC,
      0.994 [95% CI, 0.992-0.995] for intrarater variability; and CCC >=0.99 for each
      center for inter-rater variability). Moreover, regardless of the operator
      measuring the VLUs, the reliability of image capture and image quality remained
      excellent. CONCLUSIONS: The 3D LifeViz digital imaging system is a noncontact
      stereophotographic method that provides measurements of VLU area or changes in
      VLU areas that are as accurate and reliable as those obtained using the
      planimetry method and in conditions as close as possible to those of a clinical
      trial.

PMID- 29037357
TI  - Topical timolol promotes healing of chronic leg ulcer.
AB  - BACKGROUND: Chronic ulcers are a common problem, with chronic diabetic and venous
      ulcers forming a large proportion. This is the first case-control study to assess
      the effect of topical timolol on healing of chronic venous and chronic diabetic
      ulcers. METHODS: The study included 60 patients with chronic leg ulcers. The
      ulcers in the study group (n = 30) were treated with topical 0.5% timolol maleate
      solution along with antibiotics and dressings; those in the control group (n =
      30) received only antibiotics and dressings. The ulcers in both groups were
      evaluated at 4, 8, and 12 weeks, and ulcer area was calculated. Healing rate was
      assessed by calculating the percentage change in ulcer area. RESULTS: The mean
      percentage change in area at 4, 8, and 12 weeks was 25.29, 43.77, and 61.79 in
      the study group and 11.92, 22.40, and 29.62 in the control group. Analysis showed
      that there were significant differences in percentage change in ulcer of the
      study and control groups at all three time points and also within the groups. The
      type of ulcer, history of alcohol consumption, and smoking did not affect the
      healing rates in the study group. CONCLUSIONS: Topical beta-blockade using
      timolol improves the healing of chronic leg ulcers.

PMID- 29037354
TI  - Baseline factors affecting closure of venous leg ulcers.
AB  - OBJECTIVE: The objective of this study was to characterize factors associated
      with closure of venous leg ulcers (VLUs) in a pooled analysis of subjects from
      three randomized clinical trials. METHODS: Closure of VLUs after treatment with
      HP802-247, an allogeneic living cell therapy consisting of growth-arrested human
      keratinocytes and fibroblasts, vs standard therapy with compression bandaging was
      evaluated in three phase 3 clinical trials of similar design. Two trials enrolled
      subjects with VLUs ranging from 2 cm2 to 12 cm2 in area with 12-week treatment
      periods; the third trial enrolled subjects with VLUs between >12 cm2 and <=36 cm2
      with a 16-week treatment period. The first trial went to completion but failed to
      demonstrate a benefit to therapy with HP802-247 compared with placebo, and
      because of this, the remaining trials were terminated before completion. On the
      basis of no differences in outcomes between groups, subjects from both HP802-247
      and control groups were pooled across all three studies. Cox proportional hazards
      regression analysis was employed to evaluate factors associated with VLU closure.
      RESULTS: This analysis included data from 716 subjects with VLU. Factors
      evaluated for association with healing included age, gender, race, diabetes,
      glycated hemoglobin level, body mass index, treatment (HP802-247 vs compression
      alone), and ulcer characteristics including location and area and duration at
      baseline. In an initial model including all of these putative factors, the
      following were significant at the P < .10 level: diagnosis of diabetes mellitus,
      gender, wound location (ankle or leg), baseline wound area, and wound duration at
      baseline. In a final model including only these factors, all but diabetes
      mellitus were significant at the P < .05 level. Effect sizes were as follows
      (hazard ratio [95% confidence interval]): female gender (1.384 [1.134-1.690]),
      wound location on the leg (1.490 [1.187-1.871]), smaller wound area at baseline
      (0.907 [0.887-0.927]), and shorter wound duration at baseline (0.971 [0.955
      0.987]). CONCLUSIONS: Factors associated with VLU lesions including location,
      area, and duration were important predictors of healing. Women were more likely
      than men to achieve wound closure. Factors including body mass index, the
      presence of diabetes mellitus, and higher concentrations of glycated hemoglobin
      were not significant independent predictors of wound closure in this analysis.

PMID- 29037358
TI  - Superimposition of elastic and nonelastic compression bandages.
AB  - OBJECTIVE: The objective of this study was to investigate the pressure applied by
      superimposed bandages and to compare it with the pressure applied by single
      component bandages. METHODS: Six different bandages, composed of one elastic
      bandage, one nonelastic bandage, or both, were applied in a spiral pattern on
      both legs of 25 patients at risk of venous thrombosis as a consequence of central
      or peripheral motor deficiency. Pressure was measured at four measurement points
      on the leg (B1 and C on the medial and lateral sides of the leg) and in three
      positions: supine, sitting, and standing. RESULTS: The two single bandages
      applied similar pressure in the supine position. Their superimposition showed
      different pressure levels (P < .05) but similar static stiffness index, depending
      on the order in which the bandage components were applied on the leg. The highest
      interface pressure was measured at point B1 on the medial side of the leg. This
      point also showed the highest pressure increase from supine to standing position.
      The pressure applied by the superimposition of two bandages was computed as a
      linear combination of the pressure applied by each single component (with a
      constant term set to 0). However, this linear combination did not properly fit
      the experimental pressure measurements. CONCLUSIONS: The order of bandage
      application showed a significant impact on interface pressure. However, the poor
      correlation between the pressure applied by each bandage component and the
      pressure resulting from their superimposition underlined the poor understanding
      of interface pressure generated by the superimposition of compression bandages
      and should lead to further investigations.

PMID- 29037359
TI  - Thigh compartment syndrome during extracorporeal life support.
AB  - OBJECTIVE: The aim of this study was to report our experience with patients on
      the extracorporeal life support system (ECLS) who presented with thigh
      compartment syndrome, a yet unreported complication. METHODS: A retrospective
      analysis was performed from April 2003 to April 2017 to identify patients who
      presented to our department for treatment of acute compartment syndrome of the
      thigh after cannulation of the ECLS through the femoral artery and vein. RESULTS:
      Five patients, aged 30 to 84 years, who developed thigh compartment syndrome
      during ECLS therapy were identified. In three patients, the cause was arterial
      malperfusion; in one patient, the cause was venous malfunction and arterial
      malperfusion due to malposition of the arterial distal leg perfusion cannula in
      the femoral vein. The fifth patient suffered impaired venous drainage. Patients
      were on ECLS for 4 +/- 2 days, and decompressive fasciotomy was performed in all
      patients 1 +/- 1 days after ECLS commencement. Thigh compartment syndrome was
      responsible for significant morbidity, including prolonged open wound therapy,
      hospitalization, and leg amputation in one patient. CONCLUSIONS: Compartment
      syndrome of the thigh is a limb- and life-threatening complication and may occur
      in patients on ECLS. Angiographic or duplex ultrasound control of adequate limb
      perfusion and correct placement of the perfusion cannulas is recommended. Also,
      awareness of and close clinical observation for thigh perfusion and compartment
      syndrome are essential in patients during ECLS therapy.

PMID- 29037360
TI  - Factors influencing peripheral venous pressure in an experimental model.
AB  - BACKGROUND: Peripheral venous hypertension and microvascular injury have merged
      as central features of chronic venous disease. Peripheral venous pressure in the
      lower limb is controlled by central and peripheral mechanisms. In the current
      manuscript, we examine the role of peripheral factors, particularly conduit
      capacitance compliance, focal stenosis, and arterial inflow into the calf.
      METHODS: An experimental venous model using Penrose tubing as a venous analogue
      was used where the aforementioned parameters could be manipulated. Volume
      pressure curves were derived in the static mode. The dynamic model attempted to
      simulate key pressure parameters of lower limb venous flow. RESULTS: Decreasing
      compliance resulted in progressive reduction of conduit capacitance affecting
      both bending and stretching regimens and the relative distribution between the
      two, rotating the volume-pressure curve toward the x-axis. Increased
      postcapillary (arterial) inflow increased conduit pressure. For a given inflow,
      pressures varied inversely to conduit caliber. Decreased compliance led to a
      smaller functional caliber at working pressures. Sideline capacitance with
      stagnant flow connected to the flow channel (simulating calf vein network) did
      not influence conduit pressure. Focal stenosis increased "venous pressure" if it
      was narrower than "optimum outflow caliber," defined as the minimum outflow
      conduit caliber required to balance inflow. Percentage stenosis as traditionally
      calculated using adjacent lumen as denominator was uncorrelated to pressure
      increase. CONCLUSIONS: Conduit pressure is increased with smaller native or
      functional (poor compliance) caliber, focal stenosis, and increased postcapillary
      inflow. Many of these features appear to be present in limbs clinically suspected
      of chronic venous disease. The importance of the geometric factor of Poiseuille
      equation in pressure effects of caliber reduction and collateralization is
      discussed.

PMID- 29037361
TI  - A novel surgical approach to symptomatic left renal vein aneurysm.
AB  - Visceral venous aneurysms are uncommon and renal vein aneurysms are among the
      rarest in this subset. Renal vein aneurysms are frequently asymptomatic, but
      patients may present with flank pain or hematuria. Complications of untreated
      visceral venous aneurysms include thrombus formation and, very rarely, rupture.
      Treatment of renal vein aneurysms ranges from watchful waiting to surgical
      repair. We describe a patient with renal vein aneurysm presenting with recurrent
      pulmonary embolus with no other identifiable source. Furthermore, we propose a
      novel surgical treatment with complete resection of the aneurysm and
      reconstruction of venous return by transposing the inferior mesenteric vein to
      the remaining left renal vein.

PMID- 29037362
TI  - Treatment of chronic headaches with internal jugular vein-to-innominate vein
      bypass.

PMID- 29037363
TI  - A systematic review and meta-analysis of two novel techniques of nonthermal
      endovenous ablation of the great saphenous vein.
AB  - BACKGROUND: Endothermal treatment of the great saphenous vein (GSV) has become
      the first-line treatment for superficial venous reflux. Nonthermal ablation has
      potential benefits for acceptability by patients and decreased risk of nerve
      injury. We performed a systematic review and meta-analysis to evaluate the
      efficacy of mechanochemical endovenous ablation (MOCA) and cyanoacrylate vein
      ablation (CAVA) for GSV incompetence. METHODS: MEDLINE, Embase, Cumulative Index
      to Nursing and Allied Health Literature, and Cochrane databases were searched for
      papers published between January 1966 and December 2016. Eligible articles were
      prospective studies that included patients treated for GSV incompetence and
      described the primary outcome. Exclusion criteria were full text not available,
      case reports, retrospective studies, small series (n < 10), reviews, abstracts,
      animal studies, studies of small saphenous vein incompetence, and recurrent GSV
      incompetence. Primary outcome was anatomic success. Secondary outcomes were
      initial technical success, Venous Clinical Severity Score, Aberdeen Varicose Vein
      Questionnaire score, and complications. RESULTS: Fifteen articles met the
      inclusion criteria. Pooled anatomic success for MOCA and CAVA was 94.7% and 94.8%
      at 6 months and 94.1% and 89.0% at 1 year, respectively. Venous Clinical Severity
      Score and Aberdeen Varicose Vein Questionnaire score significantly improved after
      treatment with MOCA and CAVA. CONCLUSIONS: These results are promising for these
      novel techniques that could serve as alternatives for thermal ablation
      techniques. However, to determine their exact role in clinical practice, high
      quality randomized controlled trials comparing these novel modalities with well
      established techniques are required.

PMID- 29037364
TI  - A national resident survey about the current state of venous education in
      vascular surgery training programs.
AB  - OBJECTIVE: The objective of this study was to characterize U.S. vascular surgery
      trainees' perceptions, case numbers, and attitudes toward venous disease
      education, as well as their intent to incorporate it into future practice. These
      data will provide us with a current snapshot of postgraduate venous education
      from a resident's perspective. METHODS: Institutional Review Board approval was
      obtained. A 13-question survey was created and distributed to all vascular
      surgery residents in the United States by SurveyMonkey. Formal electronic
      distribution remained deidentified as the surveys were e-mailed to residents from
      the Association of Program Directors in Vascular Surgery. RESULTS: Of 464
      vascular surgery trainees queried, 104 (22%) responded to the survey. The
      majority of responders (80%) were between 25 and 34 years of age, 60% were male,
      and 72% were white; 91% reported that they were in an academic training program,
      and 57% were enrolled in an integrated vascular surgery residency program.
      Postgraduate years (PGYs) of training among respondents were well represented:
      PGY 1, 14%; PGY 2, 8%; PGY 3, 14%; PGY 4, 12%; PGY 5, 9%; PGY 6, 18%; and PGY 7,
      25%. Vascular resident training experience with venous disease revealed the
      following: 63% performed <10 inferior vena cava stents, 64% performed <10 vein
      stripping/ligation procedures, and 50% performed <10 iliac stents; 92% of
      responders reported having performed <10 venous bypasses during their training.
      Experience with endothermal ablations was slightly better, with 74% of responders
      reporting having performed up to 20 cases. Case volumes for endothermal ablation,
      vein stripping/ligation, inferior vena cava stenting, and iliac stenting
      increased progressively by clinical training year among integrated vascular
      residents (P <= .02) but were relatively stable for classic 5 + 2 vascular
      fellows (P >= .67). Integrated residents reported having received more didactic
      venous education than the 5 + 2 vascular surgery fellows (P = .01). There were no
      differences in overall reported venous procedure volumes between groups (P >=
      .28). The majority of trainees (82%) acknowledged that treating venous disease is
      part of a standard vascular surgery practice, and many (75%) indicated a desire
      to have increased venous training. Despite this, 59% of responders reported plans
      to dedicate <25% of their future vascular surgery practice to venous disease.
      CONCLUSIONS: In this national survey-based study of vascular surgery trainees, we
      demonstrate a perceived weakness in venous disease case volumes and didactic
      education in residency. This training deficit is apparent in both integrated (0 +
      5) and traditional (5 + 2) training pathways. Our data suggest that expansion of
      the venous disease curriculum with clear training standards is warranted and that
      trainees would welcome such a change.

PMID- 29037365
TI  - A look ahead into Advanced Alternative Payment Models in vascular surgery.

PMID- 29037366
TI  - Oral tolerance induction in allergy: Kissing awake a sleeping beauty.

PMID- 29037367
TI  - In vitro, ex vivo, in vivo toxicology, the terminology issue.

PMID- 29037368
TI  - Developing a new individualized 3-node model for evaluating the effects of
      personal factors on thermal sensation.
AB  - Individual differences, such as weight, height, gender, age, and Basal Metabolic
      Rate (BMR), between human subjects can significantly affect body thermoregulatory
      mechanisms. Therefore, application of common population-based thermal comfort
      models cannot provide accurate results for an individual's thermal sensation.
      Based on the standard thermal models, including those of Fanger and Gagge,
      individual parameters are not considered in the evaluation of thermal sensations.
      Thus, these simplified standard models have some limitations under varied
      individual conditions. In this study, a new individualized thermal comfort model
      is presented on the basis of a simplified 3-node model. This model was developed
      by regarding the effects of individual characteristics, such as age, gender, Body
      Mass Index (BMI), and BMR on the thermal sensations of the bare and clothed parts
      of the body. A good agreement was found in the current model, which was verified
      based on the experimental data. In conclusion, the results indicated that the
      mean error in the prediction of skin temperature decreased from 1.2 degrees C to
      0.4 degrees C when using the new individual model instead of a non-individualized
      3-node model.

PMID- 29037369
TI  - Ambient temperature and humidity modulate the behavioural thermoregulation of a
      small arboreal mammal (Callicebus bernhardi).
AB  - Maintaining a constant body temperature is critical to the proper functioning of
      metabolic reactions. Behavioural thermoregulation strategies may minimize the
      cost of energetic balance when an animal is outside its thermoneutral zone. We
      investigated whether ambient temperature and relative air humidity influence the
      use of behavioural strategies by a group of Prince Bernhard's titi monkeys
      (Callicebus bernhardi) living in a forest fragment. We monitored a social group
      composed of four individuals (an adult couple and two juveniles) for 1010h from
      March to September 2015. We used the instantaneous scan sampling method to record
      the body posture, the microhabitat, and the occurrence of huddling with group
      mate(s) when animals were resting. We recorded ambient temperature and relative
      humidity in the shade every 10min with a data logger hanging at a height of
      approximately 5m. Daytime temperature ranged from 18.5 degrees C to 38.5 degrees
      C and relative humidity ranged from 21% to 97%. Titi monkeys avoided sunny places
      at higher temperatures, especially above 31 degrees C. Minimum night temperature
      did not influence the choice of resting microhabitats during the first hour after
      sunrise. Sitting was the major resting posture during the day (62%). Titi monkeys
      increased the use of heat-dissipating postures at ambient temperatures >27
      degrees C. In addition, an increase in relative humidity increased the use of
      these postures at 26 degrees C, 27 degrees C, 29 degrees C and 33 degrees C, but
      caused a decrease at 24 degrees C. On the other hand, the ambient temperature did
      not influence the occurrence of huddling. We conclude that microhabitat choice
      and postural behaviour are important for titi monkeys to prevent overheating and
      suggest that these behavioural adjustments might also be critical for other
      tropical arboreal mammals.

PMID- 29037370
TI  - Modeling warming predicts a physiological threshold for the extinction of the
      living fossil frog Calyptocephalella gayi.
AB  - Global climate change will have a greater impact on ectotherms in tropical and
      subtropical communities than at higher latitudes, because ambient temperatures
      are closer to the upper thermal limits of species. Amphibian species are highly
      dependent on external weather conditions, and the effect of global warming on
      these has been evaluated recently. The Great Chilean frog (Calyptocephalella
      gayi) is an endemic, monotypic species and genus whose conservation status is
      considered Vulnerable because of high extraction pressure for human consumption,
      lack of regulatory measures and comprehension by its consumers. Their populations
      have also declined due to the loss and destruction of their habitats. C. gayi has
      not been considered as an object of physiological study, so this large species is
      not known as one that can adapt to current environmental changes. In this study
      we analyze the thermoregulatory capacity and thermal efficiency of C. gayi to
      determine its potential for climatic adaptation. The results indicate that this
      species is strictly a thermal-conformer; its thermal efficiency and its ability
      to withstand high temperatures allow it to sustain itself under a climate change
      scenario, however, it has thermal constraints that do not allow it to withstand
      temperatures greater than 30 degrees C. By modeling its ontogenetic conditions
      mathematically, we project that the larvae are not in danger, although there is a
      group of around 4% which is very close to 30 degrees C, which is the highest
      temperature recorded for the species. However, about 40% of subadults and
      approximately 47% of adult frogs will not survive the change of ~7 degrees C
      projected for the following 85 years, which will affect future generations.

PMID- 29037371
TI  - Body temperature in premature infants during the first week of life: Exploration
      using infrared thermal imaging.
AB  - BACKGROUND: Hypothermia is a problem for very premature infants after birth and
      leads to increased morbidity and mortality. Previously we found very premature
      infants exhibit abnormal thermal patterns, keeping foot temperatures warmer than
      abdominal temperatures for their first 12h of life. PURPOSE: We explored the
      utility of infrared thermography as a non-invasive method for measuring body
      temperature in premature infants in an attempt to regionally examine differential
      temperatures. RESULTS: Our use of infrared imaging to measure abdominal and foot
      temperature for extremely premature infants in heated, humid incubators was
      successful and in close agreement using Bland and Altman technique with
      temperatures measured by skin thermistors. CONCLUSIONS: Our study methods
      demonstrated that it was feasible to capture full body temperatures of extremely
      premature infants while they were resting in a heated, humid incubator using a
      Flir SC640 infrared camera. This technology offers researchers and clinicians a
      method to examine acute changes in perfusion differentials in premature infants
      which may lead to morbidity.

PMID- 29037372
TI  - Effects of in vitro heat shock on immune cells in diet-induced obese mice.
AB  - Obesity has been associated with impaired immune responses and inflammation. The
      mechanisms underlying these immune disturbances in obesity are not yet clarified.
      This study investigated the effects of in vitro heat shock (HS) on immune cells
      from the point of view of thymocyte apoptosis and T-cell mitogen-stimulated
      splenocyte cytokine production as well as the heat shock protein 70 (HSP70)
      protein levels in diet-induced obese mice to explore a possible association
      between the disturbance of T cell immunity and HS response in obesity. Obese mice
      had increased apoptotic and necrotic thymocytes populations and increased
      splenocyte cytokine production of both proinflammatory and anti-inflammatory
      cytokines compared with lean mice. The in vitro HS at 42 degrees C decreased the
      rate of live cells in thymocytes, and the degree of the decrease was larger in
      obese mice compared with lean mice. The in vitro HS increased the intracellular
      and extracellular HSP70 protein levels in thymocytes and splenocytes, while the
      effects of obesity on the HSP70 protein levels were not obvious. The in vitro HS
      prior to T cell mitogen stimulation decreased IFN-gamma and IL-10 production by
      mitogen-stimulated splenocytes. This change in cytokine production due to HS was
      not affected by obesity. The obvious alteration of the HSP70 protein levels and
      association between cytokine production and the HS response in obesity were not
      found in this obesity model; however, our results indicate an association between
      the viability of thymocytes and an altered HS response in obesity and provide
      evidence that the increase in thymocyte apoptosis and acceleration of thymus
      involution in obesity could be, in part, due to the alteration of the HS
      response.

PMID- 29037373
TI  - Fast inverse prediction of the freezing front in cryosurgery.
AB  - Cryosurgery has become a well-established technique for the ablation of
      undesirable tissues such as tumors and cancers. The motivation for this study is
      to improve the efficacy and safety of this technique. This study presents an
      inverse heat transfer method for monitoring the motion of the freezing front from
      a cryoprobe. With the help of a thermocouple inserted into the layer of diseased
      tissue, the inverse heat transfer method estimates simultaneously the blood
      perfusion rate and the thermal conductivities of both frozen and unfrozen
      tissues. This information is then fed to the Pennes bioheat equation that: (1)
      calculates the time-varying temperature distribution inside the layer of tissue
      and (2) predicts the motion of the freezing front. The effect of the most
      influential parameters on the inverse predictions is investigated. These
      parameters are (1) the initial guesses for the unknown Levenberg-Marquardt
      polynomial parameters of the thermo-physical properties; (2) the temperature of
      the cryoprobe; (3) the heat transfer coefficient of the impinging jet of liquid
      nitrogen; and (4) the noise on the temperature data recorded by the thermocouple
      probe. Results show that the proposed inverse method is a promising alternative
      to ultrasound and Magnetic Resonance Imaging (MRI) for monitoring the motion of
      the freezing front during cryosurgery. For all the cryogenic scenarios simulated,
      the predictions of the inverse model remain accurate and stable.

PMID- 29037374
TI  - Sensitivity to cutaneous warm stimuli varies greatly in the human head.
AB  - The head has been known as the most sensitive area to temperature changes but the
      values are limited to the face. The purpose of this study was to examine
      cutaneous warm thresholds on the scalp and face of young males. Eight males
      participated in this study (24 +/- 3 yrs in age, 178.2 +/- 5.3cm in height, and
      90.0 +/- 15.4kg in body mass). All measurements were conducted in an
      environmental chamber (27 +/- 1 degrees C air temperature and 53 +/- 1% relative
      humidity). Cutaneous warm thresholds were measured on nine areas of the following
      regions: the frontal (two points on the right), parietal (a point on the right
      and the vertex, respectively), temporal (two points on the right), and occipital
      region (on the right) along with the forehead using a thermal stimulator (rate of
      temperature increase 0.1 degrees Cs-1). Skin temperatures on the nine head
      regions were monitored during the threshold test. The results showed that 1) no
      significant differences were found in initial skin temperatures among the nine
      head regions; 2) cutaneous warm detecting temperatures were significantly greater
      on the vertex (38.2 +/- 3.5 degrees C) than on the forehead (34.8 +/- 1.4 degrees
      C) and the other seven scalp regions (P < 0.05); 3) subjects detected the
      increase of 1.2 +/- 1.0 degrees C on the forehead and 1.5 +/- 1.2 degrees C on
      the occipital region as the first warmth while the vertex was the most
      insensitive to the increase of temperature (4.0 +/- 3.2 degrees C) (P < 0.05). In
      summary, the scalp region of young males was less sensitive to the temperature
      change when compared to the forehead, and the vertex was the most insensitive
      among the eight scalp regions to the temperature increase. We conclude that the
      entire head should be considered as a binary topography with the face and the
      scalp in terms of cutaneous thermal sensitivity.

PMID- 29037375
TI  - Modelling hand skin temperature in relation to body composition.
AB  - Skin temperature is a challenging parameter to predict due to the complex
      interaction of physical and physiological variations. Previous studies concerning
      the correlation of regional physiological characteristics and body composition
      showed that obese people have higher hand skin temperature compared to the normal
      weight people. To predict hand skin temperature in a different environment, a two
      node hand thermophysiological model was developed and validated with published
      experimental data. In addition, a sensitivity analysis was performed which showed
      that the variations in skin blood flow and blood temperature are most influential
      on hand skin temperature. The hand model was applied to simulate the hand skin
      temperature of the obese and normal weight subgroup in different ambient
      conditions. Higher skin blood flow and blood temperature were used in the
      simulation of obese people. The results showed a good agreement with experimental
      data from the literature, with the maximum difference of 0.31 degrees C. If the
      difference between blood flow and blood temperature of obese and normal weight
      people was not taken into account, the hand skin temperature of obese people was
      predicted with an average deviation of 1.42 degrees C. In conclusion, when
      modelling hand skin temperatures, it should be considered that regional skin
      temperature distribution differs in obese and normal weight people.

PMID- 29037376
TI  - The small heat shock protein Hsp27: Present understanding and future prospects.
AB  - Heat shock proteins are important for maintaining protein homeostasis and cell
      survival. Among different classes of highly conserved Hsps, low molecular weight
      Hsps (sHsps) have significant place, particularly Hsp27, whose role has been
      demonstrated in wide range of biological processes, including development,
      immunity, diseases and therapy. In this review, the structure and functions of
      Hsp27 and related genes, their role in different cellular processes as well as in
      stress tolerance, is highlighted.

PMID- 29037377
TI  - Thermographic imaging in sports and exercise medicine: A Delphi study and
      consensus statement on the measurement of human skin temperature.
AB  - The importance of using infrared thermography (IRT) to assess skin temperature
      (tsk) is increasing in clinical settings. Recently, its use has been increasing
      in sports and exercise medicine; however, no consensus guideline exists to
      address the methods for collecting data in such situations. The aim of this study
      was to develop a checklist for the collection of tsk using IRT in sports and
      exercise medicine. We carried out a Delphi study to set a checklist based on
      consensus agreement from leading experts in the field. Panelists (n = 24)
      representing the areas of sport science (n = 8; 33%), physiology (n = 7; 29%),
      physiotherapy (n = 3; 13%) and medicine (n = 6; 25%), from 13 different countries
      completed the Delphi process. An initial list of 16 points was proposed which was
      rated and commented on by panelists in three rounds of anonymous surveys
      following a standard Delphi procedure. The panel reached consensus on 15 items
      which encompassed the participants' demographic information, camera/room or
      environment setup and recording/analysis of tsk using IRT. The results of the
      Delphi produced the checklist entitled "Thermographic Imaging in Sports and
      Exercise Medicine (TISEM)" which is a proposal to standardize the collection and
      analysis of tsk data using IRT. It is intended that the TISEM can also be applied
      to evaluate bias in thermographic studies and to guide practitioners in the use
      of this technique.

PMID- 29037378
TI  - L-Citrulline acts as potential hypothermic agent to afford thermotolerance in
      chicks.
AB  - Recently we demonstrated that L-citrulline (L-Cit) causes hypothermia in chicks.
      However, the question of how L-Cit mediates hypothermia remained elusive. Thus,
      the objective of this study was to examine some possible factors in the process
      of L-Cit-mediated hypothermia and to confirm whether L-Cit can also afford
      thermotolerance in young chicks. Chicks were subjected to oral administration of
      L-Cit along with intraperitoneal injection of a nitric oxide synthase (NOS)
      inhibitor, NG-nitro-l-arginine methyl ester HCl (L-NAME), to examine the
      involvement of NO in the process of hypothermia. Food intake and plasma
      metabolites were also analyzed after oral administration of L-Cit in chicks. To
      examine thermotolerance, chicks were orally administered with a single dose of L
      Cit (15mmol/10ml/kg body weight) or the same dose twice within a short interval
      of 1h (dual oral administration) before the exposure to high ambient temperature
      (35 +/- 1 degrees C) for 180min. Although the rectal temperature was reduced
      following administration of L-Cit, L-NAME caused a greater reduction. L-NAME
      reduced total NO2 and NO3 (NOx) in plasma, which confirmed its inhibitory effect
      on NO. A single oral administration of L-Cit mediated a persistent state of
      hypothermia for the 300min of the study without affecting food intake. It was
      further found that plasma glucose was significantly lower in L-Cit-treated
      chicks. Dual oral administration of L-Cit, but not a single oral administration,
      afforded thermotolerance without a significant change in plasma NOx in chicks. In
      conclusion, our results suggest that L-Cit-mediated hypothermia and
      thermotolerance may not be involved in NO production. L-Cit-mediated
      thermotolerance further suggests that L-Cit may serve as an important nutritional
      supplement that could help in coping with summer heat.

PMID- 29037379
TI  - Thermoregulatory behavior and orientation preference in bearded dragons.
AB  - The regulation of body temperature is a critical function for animals. Although
      reliant on ambient temperature as a heat source, reptiles, and especially
      lizards, make use of multiple voluntary and involuntary behaviors to
      thermoregulate, including postural changes in body orientation, either toward or
      away from solar sources of heat. This thermal orientation may also result from a
      thermoregulatory drive to maintain precise control over cranial temperatures or a
      rostrally-driven sensory bias. The purpose of this work was to examine thermal
      orientation behavior in adult and neonatal bearded dragons (Pogona vitticeps), to
      ascertain its prevalence across different life stages within a laboratory
      situation and its interaction with behavioral thermoregulation. Both adult and
      neonatal bearded dragons were placed in a thermal gradient and allowed to
      voluntarily select temperatures for up to 8h to observe the presence and
      development of a thermoregulatory orientation preference. Both adult and neonatal
      dragons displayed a non-random orientation, preferring to face toward a heat
      source while achieving mean thermal preferences of ~ 33-34 degrees C.
      Specifically, adult dragons were more likely to face a heat source when at cooler
      ambient temperatures and less likely at warmer temperatures, suggesting that
      orientation behavior counter-balances local selected temperatures but contributes
      to their thermoregulatory response. Neonates were also more likely to select
      cooler temperatures when facing a heat source, but required more experience
      before this orientation behavior emerged. Combined, these results demonstrate the
      importance of orientation to behavioral thermoregulation in multiple life stages
      of bearded dragons.

PMID- 29037380
TI  - Thermoconformity strategy in the freshwater turtle Hydromedusa tectifera
      (Testudines, Chelidae) in its southern distribution area.
AB  - Ectotherm species are not capable of generating metabolic heat; therefore, they
      present different strategies for regulating their body temperatures, ranging from
      a precise degree of thermoregulation to a passive thermoconformity with ambient
      temperatures. In reptiles, aerial basking is the most common mechanism for
      gaining heat. However, among aquatic reptiles, such as freshwater turtles,
      aquatic basking is also frequent. Hydromedusa tectifera is a turtle of
      exclusively aquatic and nocturnal habits widely distributed in South America. We
      studied the relationship between body temperature (Tb) of H. tectifera and its
      habitat, and explored the effects of sex, life stage and body size and mass on
      Tb. Fieldwork was conducted in two streams of a mountain area of central
      Argentina. We recorded cloacal temperature, size and mass of 84 turtles. We also
      determined individuals' sex and life stage (adult/juvenile). Regarding ambient
      temperatures, we measured water temperature on the surface (Tsurf) and at depth
      of turtle capture (Tdepth) and air temperature. Mean Tb was 18.58 degrees C (Min
      = 10.20 degrees C; Max = 25.70 degrees C). Tsurf and Tdepth were highly
      correlated. Multi-model analysis using Akaike criterion indicated that Tb was
      strongly associated with water temperature, whereas air temperature and body size
      and mass did not show a significant effect. There was also no effect of turtle
      sex or life stage on Tb. Our results indicate that H. tectifera is a
      thermoconformer and eurythermal species. A nocturnal pattern of activity and a
      fully aquatic lifestyle are suggested as determinant factors.

PMID- 29037381
TI  - Dietary supplementation of enzymatically treated Artemisia annua could alleviate
      the intestinal inflammatory response in heat-stressed broilers.
AB  - The study was undertaken to evaluate the effects of enzymatically treated
      Artemisia annua (EA) on the intestinal inflammatory response of heat-stressed
      broilers. A total of 144 male Arbor Acres broilers aged 21 days were randomly
      divided into 3 groups with 6 replicates per group and 8 broilers in each
      replicate. The 3 treatment groups were as follows: the control group, in which
      broiler chickens were raised at 22 +/- 1 degrees C and fed basal diets, the heat
      stress (HS) and HS-EA groups, in which broiler chickens were raised at 34 +/- 1
      degrees C for 8h (0900-1700h) and 22 +/- 1 degrees C for 16h, and fed basal diets
      supplemented with 0 or 1g/kg EA, respectively. From 22 to 41 days, the heat
      treatment lasted for 20 consecutive days. Compared with the control group, HS
      increased the activity of plasma diamine oxidase (P < 0.05) and the concentration
      of intestinal interleukin-1beta, and up-regulated (P < 0.05) the mRNA expression
      of intestinal interleukin-1beta, interleukin-6, interferon-gamma, toll-like
      receptor 4 and heat shock protein 70, down-regulated (P < 0.05) jejunal zonula
      occludens-1 and ileal occluding mRNA abundances and intestinal interleukin-10 at
      both protein and transcriptional levels. However, EA treatment significantly
      decreased (P < 0.05) plasma diamine oxidase activity, the mRNA expression of heat
      shock protein 70, toll-like receptor 4, interleukin-6, interleukin-1beta and
      interferon-gamma in intestine of heat-stressed broilers, whereas upregulated (P <
      0.05) the mRNA expression of ileal occluding, jejunal zonula occludens-1 and
      occluding. In addition, both protein and transcriptional levels of interleukin-10
      in jejunum and ileum were increased (P < 0.05) by EA treatment in the HS group.
      In conclusion, dietary EA supplementation could alleviate the intestinal
      inflammatory response, and improve the intestinal barrier function in broilers
      during the heat stress period.

PMID- 29037382
TI  - Influences of dietary lipid and temperature on growth, fat deposition and
      lipoprotein lipase expression in darkbarbel catfish (Pelteobagrus vachellii).
AB  - Darkbarbel catfish (Pelteobagrus vachellii) is an important freshwater fish in
      China. Water temperature greatly influences the absorption and utilization of
      dietary lipid by fish. Response values (including growth, hepatic fat deposition,
      and gene expression) for darkbarbel catfish mediated by two factors (water
      temperature 20-34 degrees C; dietary lipid level 2-17%) were the focus of this
      study. The relationship between the two factors and the response values was
      evaluated by the response surface method using the central composite design. The
      experiment was conducted under laboratory conditions and lasted for seven weeks.
      A total of 975 experimental fish (average weight 11.75 +/- 0.17g) were selected
      and placed in 39 plastic tanks. The results showed that the linear effects of
      lipid level on feed conversion rate (FCR), hepatopancreas somatic index (HSI),
      hepatic triglycerides (TG), cholesterol (TC), and lipoprotein lipase (LPL) gene
      expression were significant (P < 0.05). The linear effects of water temperature
      on specific growth rate (SGR), HSI, TC level, and LPL mRNA expression were
      significant (P < 0.05). The quadratic effects of water temperature and lipid
      level on SGR and FCR were significant (P < 0.05). Low water temperature and low
      lipid diets significantly inhibited growth, increased HSI, and reduced hepatic TG
      and TC levels, and LPL mRNA expression. The adjusted R2 values for the SGR, FCR,
      HSI, TC, TG, and LPL mRNA regression models were 0.77, 0.85, 0.62, 0.73, 0.85,
      and 0.91, respectively. The optimal combination of water temperature and dietary
      lipid level was 27.5 degrees C and 9.2%, at which the greatest growth and FCR
      were 2.13%.d-1 and 1.31 respectively, with desirability of 0.904. These results
      indicated that water temperature may mediate the requirement and utilization of
      dietary lipid, and intervene in hepatic fat deposition. The results of this study
      can be used to help optimize the culture conditions of darkbarbel catfish.

PMID- 29037383
TI  - Regulation of pyruvate dehydrogenase (PDH) in the hibernating ground squirrel,
      (Ictidomys tridecemlineatus).
AB  - Pyruvate dehydrogenase (PDH) is a vital regulatory enzyme that catalyzes the
      conversion of pyruvate into acetyl-CoA and connects anaerobic glycolysis to
      aerobic TCA cycle. Post-translational inhibition of PDH activity via three serine
      phosphorylation sites (pS232, pS293, and pS300) regulate the metabolic flux
      through the TCA cycle, decrease glucose utilization, and facilitate lipid
      metabolism during times of nutrient deprivation. As metabolic readjustment is
      necessary to survive hibernation, the purpose of this study was to explore the
      post-translational regulation of pyruvate dehydrogenase and the expression levels
      of four mitochondrial serine/threonine kinases (PDHKs), during torpor-arousal
      cycles in liver, heart, and skeletal muscle of 13-lined ground squirrels. A
      combination of Luminex multiplex technology and western immunoblotting were used
      to measure the protein expression levels of total PDH, three phosphorylation
      sites, S232, 293, 300, and the expression levels of the corresponding PDH kinases
      (PDHK1-4) during euthermic control, entrance, late torpor, and interbout arousal.
      Liver and heart showed strong inhibitory PDH regulation, indicating a possible
      decrease in glucose utilization and a possible preference for beta-oxidation of
      fatty acids during periods of low temperature and starvation. On the contrary,
      skeletal muscle showed limited PDH regulation via phosphorylation, possibly due
      to alternate controls. Phosphorylation of PDH may play an important role in
      regulating aerobic and anaerobic metabolic responses during hibernation in the 13
      lined ground squirrel.

PMID- 29037384
TI  - A test of the thermal coadaptation hypothesis with ultimate measures of fitness
      in flour beetles.
AB  - Whole-organism performance of ectotherms depends on body temperature, which is
      tightly linked to environmental temperatures. Individuals attempting to optimize
      fitness must thus select appropriate temperatures. The thermal coadaptation
      hypothesis posits that To for traits closely linked to fitness should match
      temperatures selected by a species (Tset) and should coevolve with Tset. To may
      mismatch Tset if the thermal reaction norm for fitness is asymmetric. In this
      study, we examined six traits related to fitness in red and in confused flour
      beetles (Tribolium castaneum and T. confusum, respectively), including longevity,
      lifetime reproductive success, reproductive rate, and development time at four
      temperatures between 23 and 32 degrees C. For reproductive traits, To matched
      Tset whereas for longevity To was lower than Tset. Tribolium species have a
      strongly r-selected life history strategy, therefore reproductive traits are
      likely more tightly linked to fitness than longevity due to high predation rates
      at early life stages. We therefore provide support for the thermal coadaptation
      hypothesis for reproductive traits that are tightly linked to fitness. Our
      results highlight the importance of knowing the relationships of traits to
      fitness when studying thermal physiology.

PMID- 29037385
TI  - Temperature-dependent development of diapausing larvae of Chilo partellus
      (Swinhoe) (Lepidoptera: Crambidae).
AB  - Temperature-dependent development rate, percent diapause induction (hibernation
      at low temperature and aestivation at high temperature), and survival of
      diapausing larvae of Chilo partellus (Swinhoe, 1885) were examined on 13 constant
      temperatures ranging from 8 to 40 degrees C. Development of hibernating and
      aestivating larvae occurred from 10 to 25 degrees C and 27-38 degrees C,
      respectively. However, no development occurred at 8 degrees C and 40 degrees C.
      To determine actual thermal conditions that affect development and trigger both
      kind of diapause (hibernation and aestivation), various thermal parameters were
      estimated by fitting the development rate data to two linear (Ordinary equation
      and Ikemoto & Takai) models and thirteen non-linear models. The lower thermal
      thresholds (Tmin) for development of diapausing larvae of C. partellus were
      calculated as 9.60 degrees C and 10.29 degrees C using the ordinary linear model
      and Ikemoto & Takai model, respectively. Similarly, the thermal constants (K)
      estimated using the ordinary linear model was 333.33 degree-days and that
      estimated with Ikemoto & Takai model was 338.92 degree-days. Among the non-linear
      models, Lactin-2 followed by Lactin-1 were found to be the best as these models
      estimated the critical temperatures (Tmin, Tmax and Topt) similar to those of
      observed values. Conclusively, the Ikemoto & Takai linear model and Lactin-2
      followed by Lactin-1 non-linear models are useful and efficient for describing
      temperature-dependent development and estimating the temperature thresholds of
      diapausing larvae of C. partellus. Our findings provided fundamental information
      for estimation of thermal requirement and temperature based development models
      for diapausing larvae of C. partellus. This information will be highly useful for
      predicting the occurrence, seasonal emergence, number of generations and
      population dynamics of C. partellus.

PMID- 29037386
TI  - Influence of temperature and exercise on growth performance, muscle, and adipose
      tissue in pacus (Piaractus mesopotamicus).
AB  - The aim of this study was to evaluate the effects of temperature and swimming
      exercise on fish growth in pacus (Piaractus mesopotamicus). Pacus weighing 0.9 -
      1.9g and 2.7 - 4.2cm in standard length were cultivated at an initial density of
      120 fish m-3 in 3 recirculation systems containing 6 water tanks at a volume of
      0.5m3 each at temperatures of 24, 28 and 32 degrees C. At each temperature, three
      tanks were modified to generate exercise activity in the specimens and force the
      fish to swim under a current speed of 27.5cms-1. At the end of the experiment,
      the following metrics were evaluated: fish performance, morphometry (length,
      width, height and perimeter in different body positions), and the diameter and
      density of muscle and subcutaneous ventral adipose tissues. At 28 degrees C,
      pacus were both heavier and had greater weight gain after 240 days of
      cultivation. Additionally, exercise improved the feed conversion. An increase of
      4 degrees C (30 degrees C) did not provide any improvement in the performance of
      the fish. However, swimming exercise improved the performance of pacus, providing
      increases of 38% and a 15% improvement in feed conversion. Both temperature and
      exercise influenced the body morphology (especially in the caudal region) and the
      cellularity of white and red muscle fibers and adipocytes.

PMID- 29037387
TI  - Dual phase lag bio-heat transfer during cryosurgery of lung cancer: Comparison of
      three heat transfer models.
AB  - The Pennes bio-heat model is based on Fourier's law of heat conduction, which
      assumed that a thermal signal propagate with infinite speed. This gives
      contradiction in physical situation. Also, the hyperbolic bio-heat model
      considers the micro scale response in time, but it does not explain the micro
      scale response in space. Therefore, to consider the thermal behaviour which is
      not captured by the Fourier's law and to take into account the microstructural
      effect in space, a dual phase lag (DPL) bio-heat conduction model would be
      advantageous. In this paper, a two dimensional DPL model is proposed to study the
      phase change heat transfer process during cryosurgery of lung cancer. The
      governing equations are solved numerically by enthalpy based finite difference
      method. The non-ideal behaviour of tissue and heat source terms, metabolism and
      blood perfusion are also considered. This study is made to examine the effects of
      phase lags in heat flux and temperature gradient on interface positions and
      temperature distribution during freezing process. A comparative study of DPL,
      parabolic and hyperbolic conduction models is thoroughly investigated. It is
      found that the phase lags of temperature gradient and heat flux have significant
      effect on interface positions and temperature distribution.

PMID- 29037388
TI  - Temperature-related differences in mitochondrial function among clones of the
      cladoceran Daphnia pulex.
AB  - This study assessed the thermal sensitivity of mitochondrial respiration in the
      small crustacean Daphnia pulex. More specifically, we wanted to determine if
      clones that inhabit different latitudes and habitats showed differences in the
      thermal sensitivity of their mitochondrial function. The experimental design
      included two clones from temperate environments (Fence from Ontario and Hawrelak
      from Alberta) and two clones from subarctic environments (A24 from Manitoba and
      K154 from Quebec). The integrated mitochondrial function was measured with high
      resolution respirometry following whole-animal permeabilization. Mitochondrial
      respiration was performed under six different temperatures (10, 15, 20, 25, 30,
      and 35 degrees C) in the clone Hawrelak and at two temperatures (10 and 20
      degrees C) in the three other clones. In the clone Hawrelak, complexes I and II
      respiration showed higher sensitivity to temperature variation compared to
      complex IV respiration. Interestingly, the threshold plot showed no excess
      capacity of complex IV at 20 degrees C in this clone. The clones showed
      significant divergence in the ability to oxidize the complex I and complex IV
      substrates relative to the maximal oxidative phoshorylation capacity of
      mitochondria. More importantly, some of the clonal divergences were only detected
      under low assay temperatures, pointing toward the importance of this parameter in
      comparative studies. Future and more complex studies on clones from wider
      environmental gradients will help to resolve the link between mitochondrial
      function and adaptations of organisms to particular conditions, principally
      temperature.

PMID- 29037389
TI  - Lower critical temperature and cold-induced thermogenesis of lean and overweight
      humans are inversely related to body mass and basal metabolic rate.
AB  - It is colloquially stated that body size plays a role in the human response to
      cold, but the magnitude and details of this interaction are unclear. To explore
      the inherent influence of body size on cold-exposed metabolism, we investigated
      the relation between body composition and resting metabolic rate in humans at
      thermoneutrality and during cooling within the nonshivering thermogenesis range.
      Body composition and resting energy expenditure were measured in 20 lean and 20
      overweight men at thermoneutrality and during individualized cold exposure.
      Metabolic rates as a function of ambient temperature were investigated
      considering the variability in body mass and composition. We observed an inverse
      relationship between body size and the lower critical temperature (LCT), i.e. the
      threshold where thermoneutrality ends and cold activates thermogenesis. LCT was
      higher in lean than overweight subjects (22.1 +/- 0.6 vs 19.5 +/- 0.5 degrees C,
      p < 0.001). Below LCT, minimum conductance was identical between lean and
      overweight (100 +/- 4 vs 97 +/- 3kcal/ degrees C/day respectively, p = 0.45).
      Overweight individuals had higher basal metabolic rate (BMR) explained mostly by
      the higher lean mass, and lower cold-induced thermogenesis (CIT) per degree of
      cold exposure. Below thermoneutrality, energy expenditure did not scale to lean
      body mass. Overweight subjects had lower heat loss per body surface area (44.7 +/
      1.3 vs 54.7 +/- 2.3kcal/ degrees C/m2/day, p < 0.001). We conclude that larger
      body sizes possessed reduced LCT as explained by higher BMR related to more lean
      mass rather than a change in whole-body conductance. Thus, larger individuals
      with higher lean mass need to be exposed to colder temperatures to activate CIT,
      not because of increased insulation, but because of a higher basal heat
      generation. Our study suggests that the distinct effects of body size and
      composition on energy expenditure should be taken in account when exploring the
      metabolism of humans exposed to cold.

PMID- 29037390
TI  - Effect of feeding Rumen-protected capsule containing niacin, K2SO4, vitamin C,
      and gamma-aminobutyric acid on heat stress and performance of dairy cows.
AB  - This study was conducted to evaluate the effects of supplemental rumen-protected
      capsule (RPC) on animal performance, serological indicators, and serum heat shock
      protein 70 (HSP70) of lactating Holstein cows under heat stress (HS). During
      summer months, 30 healthy multiparous lactating Holstein cows with a parity
      number of 3.1 +/- 0.44, 70 +/- 15 d in milk, an average body weight of 622 +/-
      62kg, and an average milk yield of 32.28 +/- 0.96kg/d, were used. The cows were
      randomly allocated to two groups: a control group and an RPC-supplemented group
      (0.13373kg K2SO4, 0.02488kg vitamin C, 0.021148kg niacin, and 0.044784kggamma
      aminobutyric acid per cow). During the 42-d experiment, ambient air temperature
      and relative humidity inside and outside the barn were recorded hourly every day
      for the determination of temperature-humidity index (THI). Milk and blood samples
      were collected every week, and body weight and body condition scoring were
      measured on day 0. Based on the THI values, the animals had moderate HS. On day
      42, the RPC group had lower HSP70, adrenocorticotropic hormone (P = 0.0001),
      lactate dehydrogenase (P = 0.0338), and IL-6 (P = 0.0724) levels than the control
      group, with no significant differences in creatine kinase, glucocorticoid, or IL
      2 levels. Milk yield, energy-corrected milk, and dry matter intake were higher in
      RPC than in the control group (P = 0.0196). There were no significant differences
      in milk fat or daily protein levels between the two groups; however, daily
      protein and milk fat levels were higher in the RPC group than in the control
      group (P = 0.0114 and P = 0.0665, respectively). Somatic cell counts were no
      different between the two groups. In conclusion, RPC may alleviate HS and improve
      dairy cow performance.

PMID- 29037391
TI  - Intraspecific geographic variation in thermal limits and acclimatory capacity in
      a wide distributed endemic frog.
AB  - Intraspecific variation in physiological traits and the standard metabolic rate
      (SMR) is common in widely distributed ectotherms since populations at contrasting
      latitudes experiences different thermal conditions. The climatic variability
      hypothesis (CVH) states that populations at higher latitudes presents higher
      acclimation capacity than those at lower latitudes, given the wider range of
      climatic variability they experience. The endemic four-eyed frog, Pleurodema
      thaul is widely distributed in Chile. We examined the variation in maximum and
      minimum critical temperatures (CTmax and CTmin), preferred temperature (TPref),
      SMR and their acclimatory capacity in two populations from the northern and
      center of its distribution. All the traits are higher in the warmer population.
      The capacity for acclimation varies between traits and, with the exception of
      CTmax and TPref, it is similar between populations. This pattern could be
      explained by the higher daily thermal variability in desert environments, that
      increases plasticity to the levels found in the high latitude population.
      However, we found low acclimatory capacity in all physiological traits, of only
      about 3% for CTmin, 10% for CTmax and TPref, and 1% for SMR. Thus, despite the
      fact that Pleurodema thaul possess some ability to adjust thermal tolerances in
      response to changing thermal conditions, this acclimatory capacity seems to be
      unable to prevent substantial buffering when body temperatures rise. The low
      acclimatory capacity found for P. thaul suggests that this species use behavioral
      rather than physiological adjustments to compensate for environmental variation,
      by exploiting available micro-environments with more stable thermal conditions.

PMID- 29037392
TI  - Temperature selection by juvenile tuatara (Sphenodon punctatus) is not influenced
      by temperatures experienced as embryos.
AB  - Most reptiles thermoregulate to achieve body temperatures needed for biological
      processes, such as digestion and growth. Temperatures experienced during
      embryogenesis may also influence post-hatching growth rate, potentially through
      influencing post-hatching choice of temperatures. We investigated in laboratory
      settings whether embryonic temperatures (constant 18 degrees C, 21 degrees C and
      22 degrees C) influence selected body temperatures (Tsel) of juvenile tuatara
      (Sphenodon punctatus), providing a possible mechanism for differences in growth
      rates. We found that incubation temperature does not influence Tsel. Although the
      average daily mean Tsel was 21.6 +/- 0.3 degrees C, we recorded individual Tsel
      values up to 33.5 degrees C in juvenile tuatara, which is higher than expected
      and above the panting threshold of 31-33 degrees C reported for adults. We found
      diel patterns of Tsel of juvenile tuatara, observing a general pattern of two
      apparent peaks and troughs per day, with Tsel being significantly lower around
      dawn and at 1500h than any other time. When comparing our results with other
      studies on tuatara there is a remarkable consistency in mean Tsel of ~ 21 degrees
      C across tuatara of different ages, sizes and acclimatization histories. The
      ability of juvenile tuatara to withstand a wide range of temperatures supports
      their former widespread distribution throughout New Zealand and warrants further
      investigation into their plasticity to withstand climate warming, particularly
      where they have choices of habitat and the ability to thermoregulate.

PMID- 29037393
TI  - Aerobic function in mitochondria persists beyond death by heat stress in insects.
AB  - The critical thermal maximum (CTmax) of insects can be determined using flow
      through thermolimit respirometry. It has been demonstrated that respiratory
      patterns cease and insects do not recover once the CTmax temperature has been
      reached. However, if high temperatures are maintained following the CTmax,
      researchers have observed a curious phenomenon whereby the insect body releases a
      large burst of carbon dioxide at a rate and magnitude that often exceed that of
      the live insect. This carbon dioxide release has been termed the post-mortal peak
      (PMP). We demonstrate here that the PMP is observed only at high temperatures, is
      oxygen-dependent, is prevented by cyanide exposure, and is associated with
      concomitant consumption of oxygen. We conclude that the PMP derives from highly
      active, aerobic metabolism in the mitochondria. The insect tracheal system
      contains air-filled tubes that reach deep into the tissues and allow mitochondria
      access to oxygen even upon organismal death. This unique condition permits the
      investigation of mitochondrial function during thermal failure in a manner that
      cannot be achieved using vertebrate organisms or in vitro preparations.

PMID- 29037394
TI  - Selection and inheritance of developmental variants of Propylea dissecta under
      thermal stress conditions.
AB  - The present study aims to understand the influence of two thermal extremes (15
      degrees C and 35 degrees C) as thermal stressors on the selected line of
      developmental variants (slow and fast developers) in Propylea dissecta and to
      compare it with the response at the optimal temperature (27 degrees C). The ratio
      of slow and fast developers within an egg batch differed with thermal extremes
      irrespective of F1 and F15 generations. Adult body mass got depressed after
      selection for control slow developers at 15 degrees C while it got enhanced for
      selected fast developers at 35 degrees C. More selected slow developers were
      found at low temperature and more selected fast developers at high temperature.
      Selection probably favours the enhancement of immature survival and emergence
      ratio which was found to be highest for selected fast developers at 35 degrees C
      and selected slow developers at 15 degrees C. Population level disparity on
      thermal confliction was observed in ladybird post selection over several
      generations. Therefore, we put forward that exposure thermal extremes over a long
      duration, causes an adaptive differentiation in thermal responses of slow and
      fast developers.

PMID- 29037395
TI  - Diurnal temperature range and mortality in Urmia, the Northwest of Iran.
AB  - Diurnal Temperature Range (DTR) is a meteorological index which represents
      temperature variation within a day. This study assesses the impact of high and
      low values of DTR on mortality. Distributed Lag Non-linear Models combined with a
      quasi-Poisson regression model was used to assess the impact of DTR on cause, age
      and gender specific mortality, controlled for potential confounders such as long
      term trend of daily mortality, day of week effect, holidays, mean temperature,
      humidity, wind speed and air pollutants. As the effect of DTR may vary between
      the hot season (from May to October) and cold season (from November to April of
      the next year), we conducted analyses separately for these two seasons. In high
      DTR values (all percentiles), the Cumulative Relative Risk (CRR) of Non
      Accidental Death, Respiratory Death and Cardiovascular Death increased in the
      full year and hot season, and especially in lag (0-6) of the hot season. In the
      cold season and high DTR values (all percentiles), the CRR of Non-Accidental
      Death and Cardiovascular Death decreased, but the CRR of Respiratory Death
      increased. Although there was no clear significant effect in low DTR values. High
      values of DTR increase the risk of mortality, especially in the heat season, in
      Urmia, Iran.

PMID- 29037396
TI  - Maternal exposure to ambient air temperature during pregnancy and early childhood
      pneumonia.
AB  - BACKGROUND: Pneumonia has been widely recognized as the leading cause of death in
      children worldwide, but its etiology still remains unclear. OBJECTIVE: We
      examined the association between maternal exposure to ambient air temperature
      during pregnancy and lifetime pneumonia in the offspring. METHODS: We conducted a
      cohort study of 2598 preschool children aged 3-6 years in Changsha, China. The
      lifetime prevalence of pneumonia was assessed using questionnaire. We backwards
      estimated each child's exposure to air temperature during prenatal and postnatal
      periods. Multiple regression model was used to examine the association between
      childhood pneumonia and exposure to air temperature in terms of odd ratios (OR)
      and 95% confidence interval (CI). RESULTS: Prevalence of childhood pneumonia in
      Changsha was high up to 38.6%. We found that childhood pneumonia was
      significantly associated with prenatal exposure to air temperature, with adjusted
      OR (95% CI) = 1.77 (1.23-2.54) for an interquartile range (IQR) increase in
      temperature, particularly during the second trimester with adjusted OR (95% CI) =
      2.26 (1.32-3.89). Boys are more susceptible to the risk of pneumonia due to air
      temperature than girls. We further observed that maternal exposure to extreme
      heat days during pregnancy increased the risk of pneumonia in the offspring.
      CONCLUSIONS: Maternal exposure to air temperature during pregnancy, particularly
      the second trimester, was associated with pneumonia in the children, providing
      the evidence for fetal origins of pneumonia.

PMID- 29037397
TI  - Development of the embryonic heat shock response and the impact of repeated
      thermal stress in early stage lake whitefish (Coregonus clupeaformis) embryos.
AB  - Lake whitefish (Coregonus clupeaformis) embryos were exposed to thermal stress
      (TS) at different developmental stages to determine when the heat shock response
      (HSR) can be initiated and if it is altered by exposure to repeated TS. First,
      embryos were subject to one of three different TS temperatures (6, 9, or 12
      degrees C above control) at 4 points in development (21, 38, 60 and 70 days post
      fertilisation (dpf)) for 2h followed by a 2h recovery to understand the ontogeny
      of the HSR. A second experiment explored the effects of repeated TS on the HSR in
      embryos from 15 to 75 dpf. Embryos were subjected to one of two TS regimes; +6
      degrees C TS for 1h every 6 days or +9 degrees C TS for 1h every 6 days.
      Following a 2h recovery, a subset of embryos was sampled. Our results show that
      embryos could initiate a HSR via upregulation of heat shock protein 70 (hsp70)
      mRNA at all developmental ages studied, but that this response varied with age
      and was only observed with a TS of +9 or +12 degrees C. In comparison, when
      embryos received multiple TS treatments, hsp70 was not induced in response to the
      1h TS and 2h recovery, and a downregulation was observed at 39 dpf.
      Downregulation of hsp47 and hsp90alpha mRNA was also observed in early age
      embryos. Collectively, these data suggest that embryos are capable of initiating
      a HSR at early age and throughout embryogenesis, but that repeated TS can alter
      the HSR, and may result in either reduced responsiveness or a downregulation of
      inducible hsps. Our findings warrant further investigation into both the short-
      and long-term effects of repeated TS on lake whitefish development.

PMID- 29037398
TI  - Thermoregulation of male sheep of indigenous or exotic breeds in a tropical
      environment.
AB  - Climate change has intensified the frequency of heat waves in the world, thereby
      exposing farm animals to stressful conditions. For better productive performance
      it is important to identify the most resilient genotypes. Thus, our objective was
      to evaluate the thermoregulatory responses of rams of tropical indigenous (Morada
      Nova and Santa Ines) and exotic breeds (Dorper and Texel), by monitoring the
      environmental and physiological indicators related to heat tolerance. The
      experiment was carried out in a tropical climate region (Cwa), in Brazil, for
      twelve months, which comprised spring, summer, autumn and winter. Thirty-three
      rams were divided into groups: Morada Nova (MN; n=8, red-coat), Santa Ines (SI;
      n=9, black-coat), Dorper (DO; n=8, white-coat) and Texel (TX; n=8, white-coat).
      The microclimatic variables were monitored, and the THI and BGHI comfort indices
      were calculated. Coat thickness and body surface temperatures were measured
      monthly, and serum triiodothyronine-T3 measurements and complete blood tests were
      performed. The physiological variables were evaluated every fifteen days and skin
      micro-biopsies were performed in the summer and winter for histological
      evaluation. During the warmer seasons, the THI and BGHI reached values that
      indicated thermal discomfort. TX showed higher coat thickness throughout the
      year, increased physiological variables related to thermolysis, and reduced T3 (P
      < 0.05). The internal temperature was permanently lower in the MN, SI and DO (P <
      0.05). The body surface temperatures were affected by the coat characteristics
      and wool length. Hematological parameters varied in the seasons with the highest
      thermal conditions (P < 0.05). The MN showed larger sweat glands, while the area
      occupied by the sweat glands was higher in the SI. The DO showed higher hair
      density in the summer and winter (P < 0.05). The results indicated that the MN,
      SI and DO breeds overcome the thermal challenge more easily throughout the
      seasons due to specific adaptive morphological and physiological characteristics.

PMID- 29037399
TI  - Comparison of heat strain recovery in different anti-heat stress clothing
      ensembles after work to exhaustion.
AB  - A hot environment combined with physically demanding tasks can subject workers to
      a higher risk of heat stress. A series of regulations and guidelines have been
      proposed to design appropriate anti-heat stress work uniform to reduce body heat
      strain. The present study aimed to examine heat strain recovery in different anti
      heat stress clothing ensembles after work to exhaustion in the heat. 10 healthy
      males performed intermittent treadmill running/walking to exhaustion, followed by
      30min passive recovery sitting in a climatic chamber, which simulated the hot and
      humid outdoor environment (34 degrees C temperature, 60% relative humidity,
      0.3m/s air velocity, and 450W/m2 solar radiation). The participants took part in
      five wear trials in counter-balanced order, including Sportswear, CIC Uniform,
      NEW Uniform, ICEBANK Cooling Vest, and NEW Cooling Vest, which have different
      levels of cooling capacity. Core temperature, skin temperature, heart rate, sweat
      loss, ratings of perceived exertion, and thermal sensations were measured
      throughout the entire heat exposure period. Physiological heat strain indices,
      including the physiological strain index (PhSI) and the perceptual strain index
      (PeSI), were used as a yardstick to quantify and compare the rate of recovery.
      Significantly lower physiological strain was observed in the newly developed NEW
      Uniform and NEW Cooling Vest groups compared with the commonly worn CIC Uniform
      group during recovery. At the end of the recovery period, participants in NEW
      Cooling Vest achieved the highest recovery (42.18% in PhSI and 81.08% in PeSI),
      followed by ICEBANK Cooling Vest, Sportswear, NEW Uniform, and CIC Uniform. The
      cooling capacity of anti-heat stress clothing ensembles and the recovery time
      significantly affect the rate of recovery in PhSI and PeSI, which may benefit the
      industry by formulating the appropriate work-rest schedule by considering the
      clothing effect.

PMID- 29037400
TI  - Effect of chronic low body temperature on feeding and gut passage in a
      plethodontid salamander.
AB  - Although feeding in some plethodontid salamander species, such as Dusky
      Salamanders (Desmognathus, family Plethodontidae), occurs at short-term (acute)
      low temperature below 5 degrees C, it is unknown whether feeding, digestion, and
      gut passage continue to occur during periods of long-term (chronic) low
      temperature. We performed a controlled laboratory experiment to examine the
      effect of several chronic low environmental temperatures on both feeding and gut
      passage in semiaquatic Spotted Dusky Salamanders (D. conanti). We quantified
      salamander feeding and defecation for different experimental groups maintained
      for many weeks at a constant temperature of 4, 7, 10, or 13 degrees C. Although
      feeding frequency, number of prey items consumed per feeding, and defecation
      frequency were significantly less for individuals at 4 degrees C than for
      individuals at 10 or 13 degrees C, salamanders continued to feed, defecate, and
      maintain body mass for 12 weeks at 4 degrees C. The ratio of the number of fecal
      pellets produced to the number of prey items consumed each week by individuals
      did not significantly decrease at 4 degrees C, which indicates gut passage was
      sustained at this temperature. Because both time between feeding and time between
      defecation were similarly affected by prolonged low temperature, the significant
      decrease in feeding frequency at 4 degrees C may depend, in part, on a decrease
      in digestive function and an extended time for gut passage at low temperature. We
      conclude that most individuals of D. conanti can feed, digest, and maintain body
      mass for several months at constant low temperature down to 4 degrees C. Our
      results support a growing body of data that indicate some plethodontid
      salamanders may acquire energy at environmental temperatures only a few degrees
      above freezing.

PMID- 29037401
TI  - Out on a limb: Thermal microenvironments in the tropical forest canopy and their
      relevance to ants.
AB  - Small, cursorial ectotherms like ants often are immersed in the superheated air
      layers that develop millimeters above exposed, insolated surfaces (i.e., the
      thermal boundary layer). We quantified the thermal microenvironments around tree
      branches in the tropical rainforest canopy, and explored the effects of substrate
      color on the internal body temperature and species composition of arboreal ants.
      Branch temperatures during the day (09:00-16:00) were hottest (often > 50 degrees
      C) and most variable on the upper surface, while the lowest and least variable
      temperatures occurred on the underside. Temperatures on black substrates declined
      with increasing distance above the surface in both the field and the laboratory.
      By contrast, a micro-scale temperature inversion occurred above white substrates.
      Wind events (ca. 2ms-1) eliminated these patterns. Internal temperatures of
      bodies of Cephalotes atratus workers experimentally heated in the laboratory were
      6 degrees C warmer on white vs. black substrates, and 6 degrees C cooler than
      ambient in windy conditions. The composition of ant species foraging at baits
      differed between black-painted and unpainted tree branches, with a tendency for
      smaller ants to avoid the significantly hotter black surfaces. Collectively,
      these outcomes show that ants traversing canopy branches experience very
      heterogeneous thermal microenvironments that are partly influenced in predictable
      ways by branch surface coloration and breezy conditions.

PMID- 29037402
TI  - Thermal biology of eastern box turtles in a longleaf pine system managed with
      prescribed fire.
AB  - Fire can influence the microclimate of forest habitats by removing understory
      vegetation and surface debris. Temperature is often higher in recently burned
      forests owing to increased light penetration through the open understory. Because
      physiological processes are sensitive to temperature in ectotherms, we expected
      fire-maintained forests to improve the suitability of the thermal environment for
      turtles, and for turtles to seasonally associate with the most thermally-optimal
      habitats. Using a laboratory thermal gradient, we determined the thermal
      preference range (Tset) of eastern box turtles, Terrapene carolina, to be 27-31
      degrees C. Physical models simulating the body temperatures experienced by
      turtles in the field revealed that surface environments in a fire-maintained
      longleaf pine forest were 3 degrees C warmer than adjacent unburned mixed
      hardwood/pine forests, but the fire-maintained forest was never of superior
      thermal quality owing to wider Te fluctuations above Tset and exposure to extreme
      and potentially lethal temperatures. Radiotracked turtles using fire-managed
      longleaf pine forests maintained shell temperatures (Ts) approximately 2 degrees
      C above those at a nearby unburned forest, but we observed only moderate seasonal
      changes in habitat use which were inconsistent with thermoregulatory behavior. We
      conclude that turtles were not responding strongly to the thermal heterogeneity
      generated by fire in our system, and that other aspects of the environment are
      likely more important in shaping habitat associations.

PMID- 29037403
TI  - Analytical expressions for estimating endurance time and glove thermal resistance
      related to human finger in cold conditions.
AB  - Frostbite is considered the severest form of cold injury and can lead to necrosis
      and loss of peripheral appendages. Therefore, prediction of endurance time of
      limb's tissue in cold condition is not only necessary but also crucial to
      estimate cold injury intensity and to choose appropriate clothing. According to
      the previous work which applied a 3-D thermal model for human finger to analyze
      cold stress, in this study, an expression is presented for endurance time in cold
      conditions to prevent cold injury. A formula is also recommended to select a
      proper glove with specific thermal resistance based on the ambient situation and
      cold exposure time. By employing linear extrapolation and real physical
      conditions, the proposed formulas were drawn out from numerical simulation.
      Analytical results show good agreement with numerical data. The used numerical
      data had been also validated with experimental data existed in the literature.
      Furthermore, the effect of different parameters such as glove thermal resistance
      and ambient temperature is investigated analytically.

PMID- 29037404
TI  - Do the ornamented osteoderms influence the heat conduction through the skin? A
      finite element analysis in Crocodylomorpha.
AB  - In order to assess the implication of the crocodylomorph ornamented osteoderms on
      the skin conduction during basking, we have performed three dimensional modeling
      and finite element analyses on a sample which includes both extant dry bones and
      well-preserved fossils tracing back to the Early Jurassic. In purpose to reveal
      the possible implication of the superficial ornamentation on the osteoderm heat
      conduction, we repeated the simulation on an equivalent set of smoothed 3D
      modeled osteoderms. The comparison of the results evidenced that the presence of
      the apical sculpture has no significant impact on the osteoderm global
      conduction. Furthermore, as we also aimed to assess the influence of the inner
      bone porosity on the osteoderm conduction, we modified the heat equation
      parameters so that the 3D-modeled osteoderms successively score the compact and
      the cancellous bone properties (i.e. mass density, heat capacity, thermal
      conductivity and thermal diffusivity). Finally, we repeated the analyses using
      the soft-dermis properties which lead to outline that neither the degree of
      porosity nor the presence of the osteoderms (in itself) significantly modifies
      the heat conduction through the crocodylomorph skin. Consequently, as
      hypothesized by previous authors, if the dermal shield happens to be involved
      into heat capture during basking for crocodylians, this process must mainly rely
      on a convective effect based on the osteoderm relative degree of vascularization.
      This last assumption could thus explain why the crocodylians which produce little
      metabolic heat would carry an entire vascularized osteoderm shield.

PMID- 29037405
TI  - Relevance of body size and shell colouration for thermal absorption and heat loss
      in white garden snails, Theba pisana (Helicidae), from Northern France.
AB  - The internal temperature of land snails depends on environmental factors, such as
      exposure to electromagnetic radiation and airflow as well as biotic factors
      including shell size, shell colouration and thickness or the resting position of
      the snail. In controlled field experiments, we quantified heating by thermal
      absorption of light and airflow-induced heat loss in the white garden snail,
      Theba pisana, from Normandy, France. Heating experiments revealed a significant
      positive relation of the internal body temperature with illumination period,
      shell temperature and air temperature at different times of day. The size of the
      snails was negatively related with both of the given illumination times: smaller
      animals heated up stronger than larger ones. The temperature at the surface of
      the shell significantly depended on the illumination period and the time of day.
      An AIC-based quality assessment of multiple linear modelling showed that, for
      explaining both shell surface and internal temperature of the soft body, several
      factors, i.e., exposure time, daytime, shell size and colouration contributed to
      the best models, respectively. Similarly, heat loss of the soft body after and
      during exposure of the snails to sunlight by a constant airflow depended on the
      initial body temperature, shell size, colouration and ambient air temperature.
      Our study revealed also the importance of both shell size and colouration for the
      loss of body temperature under natural conditions: small and banded animals that
      had heated up to temperatures above 30 degrees C cooled down faster than large
      and un-banded ones.

PMID- 29037406
TI  - Monitoring changes in body surface temperature associated with treadmill exercise
      in dogs by use of infrared methodology.
AB  - The aim of this study was to evaluate the influence of moderate treadmill
      exercise session on body surface and core temperature in dog measured by means of
      two infrared instruments. Ten Jack Russell Terrier/Miniature Pinscher mixed-breed
      dogs were subjected to 15min of walking, 10min of trotting and 10min of gallop.
      At every step, body surface temperature (Tsurface) was measured on seven regions
      (neck, shoulder, ribs, flank, back, internal thigh and eye) using two different
      methods, a digital infrared camera (ThermaCam P25) and a non-contact infrared
      thermometer (Infrared Thermometer THM010-VT001). Rectal temperature (Trectal) and
      blood samples were collected before (T0) and after exercise (T3). Blood samples
      were tested for red blood cell (RBC), hemoglobin concentration (Hb) and
      hematocrit (Hct). A significant effect of exercise in all body surface regions
      was found, as measured by both infrared methods. The temperature obtained in the
      eye and the thigh area were higher with respect to the other studied regions
      throughout the experimental period (P<0.0001). RBC, Hb, Hct and Trectal values
      were higher at T3 (P<0.05). Statistically significant higher temperature values
      measured by infrared thermometer was found in neck, shoulder, ribs, flank, back
      regions respect to the values obtained by digital infrared camera (P<0.0001). The
      results obtained in this study showed that both internal and surface temperatures
      are influenced by physical exercise probably due to muscle activity and changes
      in blood flow in dogs. Both infrared instruments used in this study have proven
      to be useful in detecting surface temperature variations of specific body
      regions, however factors including type and color of animal hair coat must be
      taken into account in the interpretation of data obtained by thermography
      methodology.

PMID- 29037407
TI  - Serum concentrations of free amino acids in growing pigs exposed to diurnal heat
      stress fluctuations.
AB  - In areas where the ambient temperature (AT) is above the thermo neutral (TN) zone
      of pigs, significant changes within a 24-h period occur, differently affecting
      the availability of amino acids (AA) within the same day. An experiment was
      conducted to analyze the serum concentrations (SC) of free AA in pigs exposed to
      diurnal variations in AT. Six pigs (27.1 +/-1.3kg body weight) implanted with a
      thermometer to register the body temperature (BT) at 15-min intervals were used.
      Blood samples were collected on the last 3 d of the 14-d study, at 0700h (lowest
      AT), 1200h (mild HS), and 1600h (severe HS). The pigs received 1.2kg/d of an AA
      supplemented, wheat-soybean meal diet, in two equal meals (0700 and 1900h). The
      AT and BT, recorded at 0700, 1200, and 1600h was: 30.6, 38.6, 41.1 degrees C, and
      38.2, 39.5, 40.3 degrees C, respectively. The BT was significantly correlated (P
      < 0.001) with the AT. The SC (MUM/mL) of Ile, Lys, Met, Val, Ala, Asn, and Pro
      were higher (P <= 0.01); Arg, Phe, Glu, and Tyr tended to be higher (P <= 0.10);
      but Cys was lower (P < 0.05) at 1200h than at 0700h. Lys was higher, Cys and Tyr
      were lower (P < 0.05), and Ile and Val tended to be higher (P <= 0.10) at 1600h
      than at 0700h. Serum Arg, Ile, Phe, Ala, Asn, Gln, Pro, Ser, and Tyr were lower
      (P < 0.05), and Leu and Val tended to be lower at 1600h than at 1200h. These data
      demonstrate that AT directly alters the BT of pigs, and that diurnal variations
      in AT differently affect their SC and availability of AA for growth.

PMID- 29037408
TI  - Epigenetic control of cyp19a1a expression is critical for high temperature
      induced Nile tilapia masculinization.
AB  - In fish species with temperature-dependent sex determination (TSD) or genotypic
      sex determination plus temperature effects (GSD + TE), temperature can either
      affect sex differentiation or determine the sex. However, it is unknown if
      epigenetic control of cyp19a1a expression is critical for high temperature
      induced masculinization in the freshwater fish Nile tilapia. We analyzed the
      cyp19a1a DNA methylation levels in three age groups and found that they were
      lower in females than in males. At 8 months of age, males had DNA methylation
      levels of the cyp19a1a promoter that were almost twice as high as those of
      females. Exposure to high temperatures increased the cyp19a1a promoter DNA
      methylation levels from 30.87 +/- 4.56% to 48.34 +/- 0.92% (P = 0.035) in females
      and from 50.33 +/- 7.38% to 51.66 +/- 4.75% in males (P = 0.867). The increases
      in the cyp19a1a promoter DNA methylation levels were associated with the mRNA
      expression levels and might play a role in promoting gonadal differentiation in
      high temperature induced group females toward the male pathway. Western blot
      analysis revealed that the cyp19a1a protein expression levels in females
      significantly declined after high temperature treatment; only a slight decline
      was recorded in male fish. These results reveal that epigenetic control of
      cyp19a1a mRNA and protein expression is related to the environmental temperature
      and sex ratios in fish with TSD or GSD + TE.

PMID- 29037409
TI  - Thermotolerance, health profile and cellular expression of HSP90AB1 in Nguni and
      Boran cows raised on natural pastures under tropical conditions.
AB  - Boran (n=15) and Nguni (n=15) cows were used in a study to determine the effect
      of breed, age and coat colour on the concentration of heat shock protein 90
      (HSP90AB1), physiological rectal and skin temperature, and markers of health. The
      cows were exposed to summer heat stress and Boran cows had higher significant
      (P<0.05) skin temperature (35.1+/-0.42 degrees C) as compared to the Nguni cows
      (36.0+/-0.38 degrees C). Nguni cows had higher body thermal gradients than the
      Boran cows. Boran cows had thicker skin (P<0.05) and longer hairs (24.3+/-2.26mm)
      than their Nguni counterparts (20.2+/-2.00mm). The HSP90AB1 concentration was
      increased in Boran cows, although breed had no significant (P>0.05) influence.
      Significantly (P<0.05) high urea and total cholesterol was recorded in Boran
      cows. Coat colour had a significant (P<0.05) effect on the weight and rectal
      temperature of the study animals. Coat colour and age had no significant effect
      (P>0.05) on the concentration of HSP90AB1, although older cows (>=9 years) had
      higher concentrations (5.4+/-1.29ng/ml). Age had a significant (P<0.05) effect on
      packed cell volume, neutrophil/lymphocyte, urea, total protein and gamma-glutamyl
      transferase whereas cows with >=9 years had more concentrations than young ones.
      Age significantly (P<0.05) influenced hair length, skin temperature and the
      thermal gradients. Breed was positively correlated (P<0.001) to coat colour, age,
      body condition score, weight and temperature humidity index while negatively
      correlated to urea and total cholesterol. It was concluded that Nguni cows were
      more adaptable to hot environments than the Boran cows as the latter were unable
      to balance thermal load between their bodies and the environment.

PMID- 29037410
TI  - Heat adaptation from regular hot water immersion decreases proinflammatory
      responses, HSP70 expression, and physical heat stress.
AB  - Hot-water immersion (HWI) is a type of thermal therapy for treating various
      diseases. In our study, the physiological responses to occasional and regular HWI
      have been explored. The rats were divided into a control group, occasional group
      (1D), and regular group (7D). The 1D and 7D groups received 42 degrees C during
      15mins HWI for 1 and 7 days, respectively. The blood samples were collected for
      proinflammatory cytokines examinations, the heart, liver and kidney were excised
      for subsequent IHC analysis to measure the level of heat shock protein 70
      (HSP70). The results revealed that the body temperature increased significantly
      during HWI on Day 3 and significantly declined on Days 6 and 7. For the 7D group,
      body weight, heart rate, hematocrit, platelet, osmolarity, and lactate level were
      lower than those in the 1D group. Furthermore, the levels of granulocyte counts,
      tumor necrosis factor-alpha, and interleukin-6 were lower in the 7D group than in
      the 1D group. The induction of HSP70 in the 1D group was higher than in the other
      groups. Physiological responses to occasional HWI are disadvantageous because of
      heat stress. However, adaptation to heat from regular HWI resulted in decreased
      proinflammatory responses and physical heat stress.

PMID- 29037411
TI  - Thermal adaptation in North American cicadas (Hemiptera: Cicadidae).
AB  - We determine and summarize the thermal responses for 118 species and subspecies
      of North American cicadas representing more than 50 years of fieldwork and
      experimentation. We investigate the role that habitat and behavior have on the
      thermal adaptation of the North American cicadas. There are general patterns of
      increasing thermal responses in warmer floristic provinces and increasing maximum
      potential temperature within a habitat. Altitude shows an inverse relationship
      with thermal responses. Comparison of thermal responses of species emerging early
      or late in the season within the same habitat show increases in the thermal
      responses along with the increasing environmental temperatures late in the
      summer. However, behavior, specifically the use of endothermy as a
      thermoregulatory strategy, can influence the values determined in a particular
      habitat. Subspecies generally do not differ in their thermal tolerances and
      thermal tolerances are consistent within a species over distances of more than
      7600km.

PMID- 29037412
TI  - Re-evaluating the diets of Morotopithecus bishopi and Afropithecus turkanensis:
      An anterior dentognathic perspective.
AB  - Afropithecus turkanensis (17-17.5 Ma; Kalodirr, Buluk, Locherangan, Moruorot,
      Nabwal Hills; Kenya) and Morotopithecus bishopi (20.6 Ma; Moroto II; Uganda) are
      both large-bodied catarrhines from the early Miocene of eastern Africa with
      relatively primitive cranial and postcanine dental morphology. They are primarily
      differentiated by a temporal separation of ~3.6 million years and by postcranial
      samples suggesting that M. bishopi was capable of orthograde postures and below
      branch arboreality, while A. turkanensis was most likely a pronograde quadruped.
      Several researchers dispute the validity of the postcranial and dating evidence
      and argue that M. bishopi and A. turkanensis may be congeneric or even
      conspecific. Although A. turkanensis possesses a derived suite of specialized
      anterior dentognathic characters that are functionally convergent with extant
      pitheciins and associated with sclerocarp foraging and maxillary canine dietary
      function, a similar analysis of M. bishopi anterior dentognathic anatomy is
      presently lacking. The current study addresses this shortcoming via a detailed
      morphometric analysis of relevant A. turkanensis and M. bishopi specimens
      preserving the anterior palate, maxillary canines and incisors. Results indicate
      that the anterior dentognathic morphologies of A. turkanensis and M. bishopi are
      distinct and represent significantly dissimilar feeding adaptations.
      Specifically, M. bishopi lacks the elongated and anteriorly narrow premaxilla,
      lateral incisors that are more posterior and mesially positioned relative to the
      central incisors, and pronounced yet evenly distributed mesial curvature of the
      maxillary canine that are shared by A. turkanensis and extant pitheciins. Given
      that A. turkanensis anterior dentognathic morphology is functionally convergent
      with extant pitheciins to the exclusion of M. bishopi, it is likely that M.
      bishopi and A. turkanensis have dissimilar feeding adaptations. Although a
      systematic analysis is required to verify these species at the generic and
      species level, the absence of any substantial morphological similarity in their
      anterior dentognathic anatomy is most consistent with the interpretation that M.
      bishopi and A. turkanensis represent, at the least, different species.

PMID- 29037413
TI  - Extant ape dental topography and its implications for reconstructing the
      emergence of early Homo.
AB  - Dental topography reflects diet accurately in several extant and extinct
      mammalian clades. However, dental topographic dietary reconstructions have high
      success rates only when closely related taxa are compared. Given the dietary
      breadth that exists among extant apes and likely existed among fossil hominins,
      dental topographic values from many species and subspecies of great apes are
      necessary for making dietary inferences about the hominin fossil record. Here, we
      present the results of one metric of dental topography, Dirichlet normal energy
      (DNE), for seven groups of great apes (Pongo pygmaeus pygmaeus, Pan paniscus, Pan
      troglodytes troglodytes and schweinfurthii, Gorilla gorilla gorilla, Gorilla
      beringei graueri and beringei). Dirichlet normal energy was inadequate at
      differentiating folivores from frugivores, but was adequate at predicting which
      groups had more fibrous diets among sympatric African apes. Character
      displacement analyses confirmed there is substantial dental topographic and
      relative molar size (M1:M2 ratio; length, width, and area) divergence in
      sympatric apes when compared to their allopatric counterparts, but character
      displacement is only present in relative molar size when DNE is also considered.
      Presence of character displacement is likely due to indirect competition over
      similar food resources. Assuming similar ecological conditions in the Plio
      Pleistocene, the derived masticatory apparatuses of the robust australopiths and
      early Homo may be due to indirect competition over dietary resources between the
      taxa, causing dietary niche partitioning. Our results imply that dental
      topography cannot be used to predict dietary categories in fossil hominins
      without consideration of ecological factors, such as dietary and geographic
      overlap. In addition, our results may open new avenues for understanding the
      community compositions of early hominins and the formation of specific ecological
      niches among hominin taxa.

PMID- 29037414
TI  - Chimpanzee vertebrate consumption: Savanna and forest chimpanzees compared.
AB  - There is broad consensus among paleoanthropologists that meat-eating played a key
      role in the evolution of Homo, but the details of where, when, and why are hotly
      debated. It has been argued that increased faunivory was causally connected with
      hominin adaptation to open, savanna habitats. If savanna-dwelling chimpanzees eat
      meat more frequently than do forest chimpanzees, it would support the notion that
      open, dry, seasonal habitats promote hunting or scavenging by hominoids. Here we
      present observational and fecal analysis data on vertebrate consumption from
      several localities within the dry, open Ugalla region of Tanzania. Combining
      these with published fecal analyses, we summarize chimpanzee vertebrate
      consumption rates, showing quantitatively that savanna chimpanzee populations do
      not differ significantly from forest populations. Compared with forest
      populations, savanna chimpanzees consume smaller vertebrates that are less likely
      to be shared, and they do so more seasonally. Analyses of chimpanzee hunting that
      focus exclusively on capture of forest monkeys are thus difficult to apply to
      chimpanzee faunivory in open-country habitats and may be misleading when used to
      model early hominin behavior. These findings bear on discussions of why
      chimpanzees hunt and suggest that increases in hominin faunivory were related to
      differences between hominins and chimpanzees and/or differences between modern
      and Pliocene savanna woodland environments.

PMID- 29037415
TI  - Dental phenotypic shape variation supports a multiple dispersal model for
      anatomically modern humans in Southeast Asia.
AB  - The population history of anatomically modern humans (AMH) in Southeast Asia
      (SEA) is a highly debated topic. The impact of sea level variations related to
      the Last Glacial Maximum (LGM) and the Neolithic diffusion on past population
      dispersals are two key issues. We have investigated competing AMH dispersal
      hypotheses in SEA through the analysis of dental phenotype shape variation on the
      basis of very large archaeological samples employing two complementary
      approaches. We first explored the structure of between- and within-group shape
      variation of permanent human molar crowns. Second, we undertook a direct test of
      competing hypotheses through a modeling approach. Our results identify a
      significant LGM-mediated AMH expansion and a strong biological impact of the
      spread of Neolithic farmers into SEA during the Holocene. The present work thus
      favors a "multiple AMH dispersal" hypothesis for the population history of SEA,
      reconciling phenotypic and recent genomic data.

PMID- 29037416
TI  - The diet of open-habitat chimpanzees (Pan troglodytes schweinfurthii) in the Issa
      valley, western Tanzania.
AB  - Comparative data on the diets of extant primates inform hypotheses about hominin
      resource use. Historically, data describing chimpanzee diets stem primarily from
      forest-dwelling communities, and we lack comparative data from chimpanzees that
      live in mosaic habitats that more closely resemble those reconstructed for Plio
      Pleistocene hominins. We present data on the diet of a partially-habituated
      community of open habitat chimpanzees (Pan troglodytes schweinfurthii) from the
      Issa valley, western Tanzania, collected over a four-year period. Based mostly on
      macroscopic faecal analysis, Issa chimpanzees consumed a minimum of 69 plant
      species. There was no relationship between plant consumption and either fruit
      availability or feeding tree density; the most frequently consumed plant species
      were found in riverine forests, with woodland species consumed more frequently
      during the late dry season. We conclude by contextualising these findings with
      those of other open-habitat chimpanzee sites, and also by discussing how our
      results contribute towards reconstructions of early hominin exploitation of
      mosaic landscapes.

PMID- 29037417
TI  - Establishment of occupation chronicles in Grotte Mandrin using sooted
      concretions: Rethinking the Middle to Upper Paleolithic transition.
AB  - Soot marks, witnesses of past human activities, can sometimes be noticed in
      concretions (speleothem, travertine, carbonated crust, etc.) formed in cavities.
      We demonstrate here that these deposits, generally ignored in archaeological
      studies, turned out to be a perfectly suitable material for micro-chronological
      study of hominin activities in a site. At the Grotte Mandrin (Mediterranean
      France), thousands of clastic fragments from the rock walls were found in every
      archaeological level of the shelter. Calcareous crusts containing soot deposits
      are recorded on some of their surfaces. They appear in thin section as thin black
      laminae. Microscopic observation of these crusts revealed that they kept track of
      many occupations. We show that is possible to link them with the archaeological
      units identified during the excavation. Minimum Number of Occupations (MNO) can
      be built out of these sooted crusts. MNO are usually high and attest to the
      cumulative nature of each archaeological unit. They are witnesses of each
      occupation of hominin groups in each archaeological level of the cave. This study
      also shows that, in Grotte Mandrin, a very short time separates the first
      Middle/Upper Paleolithic transitional groups' occupations from those of the last
      Mousterians. The research perspectives on soot deposits are diversified and raise
      the possibility of studying multiple aspects of past human life, and in this
      case, to rethink the Middle/Upper Paleolithic transition, with an unmatched
      temporal resolution. Sooted concretion analysis provides high temporal resolution
      archaeology. There is a real possibility of extending this study with
      chronological implications to cavities of all ages and areas.

PMID- 29037419
TI  - [The pathologist 2.0.]

PMID- 29037418
TI  - Was Mesopithecus a seed eating colobine? Assessment of cracking, grinding and
      shearing ability using dental topography.
AB  - Extant colobine monkeys have been historically described as specialized
      folivores. However, reports on both their behavior and dental metrics tend to
      ascribe a more varied diet to them. In particular, several species, such as
      Pygathrix nemaeus and Rhinopithecus roxellana, are dedicated seasonal seed
      eaters. They use the lophs on their postcanine teeth to crack open the hard
      endocarp that protects some seeds. This raises the question of whether the
      bilophodont occlusal pattern of colobine monkeys first evolved as an adaptation
      to folivory or sclerocarpic foraging. Here, we assess the sclerocarpic foraging
      ability of the oldest European fossil colobine monkey, Mesopithecus. We use
      computed microtomograpy to investigate the three-dimensional (3D) dental
      topography and enamel thickness of upper second molars ascribed to the late
      Miocene species Mesopithecus pentelicus from Pikermi, Greece. We compare M.
      pentelicus to a sample of extant Old World monkeys encompassing a wide range of
      diets. Furthermore, we combine classic dietary categories such as folivory with
      alternative categories that score the ability to crack, grind and shear
      mechanically challenging food. The 3D dental topography of M. pentelicus predicts
      an ability to crack and grind hard foods such as seeds. This is consistent with
      previous results obtained from dental microwear analysis. However, its relatively
      thin enamel groups M. pentelicus with other folivorous cercopithecids. We
      interpret this as a morphological trade-off between the necessity to avoid tooth
      failure resulting from hard food consumption and the need to process a high
      amount of leafy material. Our study demonstrates that categories evaluating the
      cracking, grinding or shearing ability, traditional dietary categories, and
      dental topography combine well to make a powerful tool for the investigation of
      diet in extant and extinct primates.

PMID- 29037420
TI  - Discussion of: "Hospital admission unnecessary for successful uncomplicated
      radiographic reduction of pediatric intussusception".

PMID- 29037422
TI  - Digestive migration and spontaneous expulsion of a Montgomery salivar derivation
      tube.

PMID- 29037421
TI  - Discussion of: "The success of sentinel lymph node biopsy after neoadjuvant
      therapy: A single institution review".

PMID- 29037423
TI  - Unique ECG presentations and clinical management of a symptomatic LQT2 female
      carrying a novel de novo KCNH2 mutation.
AB  - A 26-year-old woman, 12 days in postpartum, developed recurrent syncope and
      cardiac arrest. Her ECG revealed QT-prolongation associated with LQT2-specific T
      U wave patterns, T wave alternans, long QT-dependent torsade de pointes (TdP) and
      ventricular fibrillation (VF). She also had intermittent LBBB (80bpm) on
      alternate beats and RBBB at sinus tachycardia (113bpm). Family genotyping
      revealed a novel de novo missense mutation G604C of KCNH2. Propranolol slowed
      heart rate and further prolonged QT interval (610ms) that caused TdP recurrence.
      Mexiletine combined with magnesium and potassium supplements prevented TdP/VF
      recurrence. This patient has remained event-free after 9-month follow-up.

PMID- 29037424
TI  - Do the arrhythmic electrocardiographic parameters merely effected by drugs or by
      anything influencing myocytes?

PMID- 29037425
TI  - Interleukin-32 may contribute to increased risk of cardiovascular disease in
      patients with hidradenitis suppurativa.

PMID- 29037426
TI  - [Cutaneous lesions secondary to hijama (wet cupping)].

PMID- 29037427
TI  - [Fibroepithelioma of Pinkus: Correlation between dermatopathology and
      dermoscopy].

PMID- 29037428
TI  - [Lymphomatoid papulosis].

PMID- 29037429
TI  - [Photo-aggravated eczema caused by methylisothiazolinone].

PMID- 29037430
TI  - Total spinal block after local anesthetic administration through the wrong access
      port of a spinal infusion pump.
AB  - We present a case reported on the SENSAR database. A patient with a spinal
      infusion pump was admitted for reservoir refill. On administration of 22ml of
      0.75% bupivacaine the patient suffered a total spinal block with widespread loss
      strength and respiratory arrest. The patient required emergency orotracheal
      intubation, mechanical ventilation and admission to ICU, where extubation was
      achieved within two hours without incidences. At a later stage it was stated that
      the local anaesthetic had been administered via the access port for bolus or
      contrast administration instead of via the access to the reservoir. Analysis of
      the incident showed up latent factors related to absence lack of personnel
      training and internal protocols. The following measures were taken: pain unit
      meeting, alert sent to SENSAR bulletin and training request for members of the
      service.

PMID- 29037431
TI  - Effect of Chlorella supplementation on cardiovascular risk factors: A meta
      analysis of randomized controlled trials.
AB  - BACKGROUND & AIMS: The effect of Chlorella supplementation on cardiovascular risk
      factors of subjects with different health status has not been conclusively
      studied. Therefore, the efficacy of Chlorella supplementation on cardiovascular
      risk factors was assessed through a meta-analysis. METHODS: A literature search
      on five electronic databases was performed and related randomized controlled
      trials (RCTs) published until 15 January 2017 were identified. For each study,
      the effect size of each outcome was presented as Un-standardized mean difference
      and 95% confidence interval (CI). The overall effect for each outcome was
      calculated using random effects model. RESULTS: Meta-analysis on 19 RCTs with 797
      subjects indicated that Chlorella administration significantly decreased the
      levels of total cholesterol (TC; -9.09 mg/dl, 95% CI: -12.91 to -5.26, P <
      0.001), low-density lipoprotein cholesterol (LDL-C; -8.32 mg/dl, 95% CI: -12.22
      to -4.42, P < 0.001), systolic blood pressure (SBP; -4.51 mmHg, 95% CI: -6.53 to 
      2.48, P < 0.001), diastolic blood pressure (DBP, -1.64 mmHg, 95% CI: -3.28 to 
      0.01, P = 0.049), and fasting blood glucose (FBG; -4.23 mg/dl, 95% CI: -8.29 to 
      0.17, P = 0.041) whereas changes in triglycerides (TG; 1.73 mg/dl, 95% CI: -7.25
      to 10.70, P = 0.706), high-density lipoprotein cholesterol (HDL-C; 1.54 mg/dl,
      95% CI: -2.40 to 5.48, P = 0.443), and body mass index (BMI; -0.23 kg/m2, 95% CI:
      -0.97 to 0.51, P = 0.545) was not statistically significant. Subgroup analyses
      based on intervention duration and Chlorella doses revealed that administration
      of Chlorella for 8 weeks or higher and doses higher than 4 g/day significantly
      reduced TC, LDL-C, SBP, and DBP levels in the participants. Moreover, Chlorella
      supplementation significantly reduced TC and LDL-C levels in unhealthy
      individuals, and also reduced SBP and DBP in hypertensive ones. CONCLUSIONS: The
      results indicated that Chlorella supplementation improved levels of TC, LDL-C,
      SBP, DBP, and FBG but the changes in TG, HDL-C, and BMI were not satisfactory.
      More precise RCTs on subjects with different health status is recommended to
      clarify the effect of Chlorella supplementation on cardiovascular risk factors.

PMID- 29037432
TI  - Acupuncture for Small Animal Neurologic Disorders.
AB  - Modern research on traditional Chinese veterinary medicine (TCVM), including
      herbal medicine and acupuncture, has made evident the role of the nervous system
      as a cornerstone in many of the mechanisms of action of TCVM. Laboratory models
      and clinical research available are supportive for the use of TCVM in the
      management of neurologic conditions in small animals, specifically in cases of
      intervertebral disk disease, other myelopathies, and painful conditions. This
      article is meant to help guide the use of TCVM for neurologic disorders in small
      animals, based on available information and recommendations from experienced TCVM
      practitioners.

PMID- 29037433
TI  - Minimally Invasive Spine Surgery in Small Animals.
AB  - Minimally invasive spine surgery (MISS) seems to have many benefits for human
      patients and is currently used for various minor and major spine procedures. For
      MISS, a change in access strategy to the target location is necessary and it
      requires intraoperative imaging, special instrumentation, and magnification. Few
      veterinary studies have evaluated MISS for canine patients for spinal
      decompression procedures. This article discusses the general requirements for
      MISS and how these can be applied to veterinary spinal surgery. The current
      veterinary MISS literature is reviewed and suggestions are made on how to apply
      MISS to different spinal locations.

PMID- 29037434
TI  - Clinical Evaluation of the Feline Neurologic Patient.
AB  - Efficient, gentle, and safe handling of cats can result in complete neurologic
      evaluations and accurate neuroanatomic localizations. The clinic environment
      should facilitate the examination by providing a quiet and secure environment for
      the cat. When direct examination of a cat is not possible, the practitioner
      should fully use indirect methods of examination and video recordings of cat
      behavior or clinical signs. Direct examination of a cat should proceed in a
      logical order, where the most useful tests are performed early on in the
      examination.

PMID- 29037435
TI  - Feline Epilepsy.
AB  - Seizures occur commonly in cats and can be classified as idiopathic epilepsy,
      structural epilepsy, or reactive seizures. Pursuit of a diagnosis may include a
      complete blood count, serum biochemistry, brain MRI, and cerebrospinal fluid
      analysis as indicated. Antiepileptic drugs should be considered if a cat is
      having frequent seizures, or any 1 seizure longer than 5 minutes. Phenobarbital
      is often the drug of choice; however, levetiracetam may be more useful for
      certain types of epilepsy in cats. Long-term prognosis depends on the underlying
      diagnosis and response to therapy.

PMID- 29037436
TI  - Which imaging before reperfusion strategy?
AB  - The ischemic penumbra is a transient and potentially reversible condition.
      Therefore, infarct progression and its counterpart penumbral salvage are highly
      variable and result from the interaction of 3 major factors: collateral flow,
      revascularization delay and success. Multimodal brain imaging now offers in
      clinical practice an exhaustive characterization of the acute ischemic injury:
      vessel site occlusion, infarction/critical hypoperfusion volume, and collateral
      flow. From 1995 to 2015, IV alteplase administered within 4.5hours after the
      onset of acute BI diagnosed by the absence of hemorrhage on a non-contrast head
      CT scan has been the only approved revascularization treatment. Over the past
      2years, 6 randomized trials have confirmed the benefit of a thrombectomy
      performed within 6-8 hours after the onset of an acute anterior BI downstream of
      an ICA/M1 occlusion. The recommended imaging modality for such patients remains a
      NCCT to exclude an hemorrhage and a CTA to confirm the proximal vessel occlusion.
      As a consequence, in the absence of collateral or penumbral imaging, studies and
      meta-analyses, have emphasized the importance of treatment delay on the outcome
      of patient after a revascularisation treatment (tPA/thrombectomy). These findings
      have supported the development of mobile stroke unit for tPA administration and
      the direct transfer of the patients eligible to thrombectomy to a comprehensive
      stroke center, bypassing primary stroke unit and sometimes conventional neuro
      imaging. In addition randomized controlled trial that did enroll patients based
      on the presence of a target mismatch on multimodal imaging demonstrated a higher
      benefit of revascularisation treatment by comparison with those who did not.This
      year the results of the randomized trial, Diffusion-weighted Imaging or
      Computerized Tomography Perfusion Assessment with Clinical Mismatch in the Triage
      of Wake-up and Late Presenting Strokes Undergoing Neurointervention with Trevo
      (DAWN)demonstrated for the first time that revascularization treatment for BI
      complicating an ICA or a proximal MCA M1 was still beneficial from 6 to 24hours
      after onset among patient who did have per their clinical exam and the multimodal
      brain imaging have a persistent penumbra. With this as a background we will
      discuss the yield of imaging for the selection of patients for a
      revascularization therapy.

PMID- 29037437
TI  - The Australian Royal Commission into Institutional Responses to Child Sexual
      Abuse.
AB  - The Royal Commission into Institutional Responses to Child Sexual Abuse is the
      largest royal commission in Australia's history and one of the largest public
      inquiries into institutional child abuse internationally. With an investment from
      the Australian government of half a billion dollars, it examined how institutions
      with a responsibility for children, both historically and in the present, have
      responded to allegations of child sexual abuse. Announced in the wake of previous
      Australian and international inquiries, public scandals and lobbying by survivor
      groups, its establishment reflected increasing recognition of the often lifelong
      and intergenerational damage caused by childhood sexual abuse and a strong
      political commitment to improving child safety and wellbeing in Australia. This
      article outlines the background, key features and innovations of this landmark
      public inquiry, focusing in particular on its extensive research program. It
      considers its international significance and also serves as an introduction to
      this special edition on the Australian Royal Commission, exploring its
      implications for better understanding institutional child sexual abuse and its
      impacts, and for making institutions safer places for children in the future.

PMID- 29037438
TI  - Tag team: Roles of miRNAs and Proteolytic Regulators in Ensuring Robust Gene
      Expression Dynamics.
AB  - Lack of prominent developmental defects arising from loss of many individual
      miRNAs is consistent with the observations of collaborative networks between
      miRNAs and roles for miRNAs in regulating stress responses. However, these
      characteristics may only partially explain the seemingly nonessential nature of
      many miRNAs. Non-miRNA gene expression regulatory mechanisms also collaborate
      with miRNA-induced silencing complex (miRISC) to support robust gene expression
      dynamics. Genetic enhancer screens have revealed roles of miRNAs and other gene
      repressive mechanisms in development or other cellular processes that were masked
      by genetic redundancy. Besides discussing the breadth of the non-miRNA genes, we
      use LIN-28 as an example to illustrate how distinct regulatory systems, including
      miRNAs and multiple protein stability mechanisms, work at different levels to
      target expression of a given gene and provide tissue-specific and stage-specific
      regulation of gene expression.

PMID- 29037440
TI  - Novel genetic loci associated HLA-B*08:01 positive myasthenia gravis.
AB  - OBJECTIVE: To identify potential causative markers involved in the development of
      early-onset myasthenia gravis (EOMG) in the MHC and non-MHC regions that may
      interact with the HLA-B*08:01 allele. METHODS: We analyzed 583 MG patients and
      identified 5 patients homozygous for the disease-associated ancestral haplotype
      8.1 (HLA-A*01:01, B*08:01, DRB1*03:01, DQB1*02:01). We also analyzed more than
      9000 controls and selected 24 for further investigation. We subsequently
      conducted a fine mapping analysis through high-throughput sequencing of the MHC
      region (from upstream of the GPalpha5 gene to downstream of the ZBTB9 gene). For
      the interaction analysis we analyzed a total of 150,090 SNPs equally distributed
      throughout the genome in the individuals that were homozygous for the main
      susceptibility HLA allele HLA-B*08:01 and investigated the expression of the
      genes located close to the observed susceptibility variants. RESULTS: The overall
      coverage of the 4.79 Mb MHC region ranged between 96.57% and 97.41%. We
      identified 705 new variants in the MHC region (673 SNPs and 32 InDels). However,
      no significant differences were found between patients and controls within the
      MHC region of the ancestral 8.1 haplotype. As the susceptibility gene is
      considered to be located close to the HLA-B locus, complete sequencing of the
      surrounding 200 kb was carried out in the 5 patients and 24 controls. No
      significant differences where observed, suggesting that the HLA-B molecule itself
      is the susceptibility factor for EOMG. We also observed two new susceptibility
      loci specific for MG HLA*08:01 patients (P < 3.33 * 10-7). These loci map to an
      intronic OVCH1 variant (rs10492374; P = 1.90 * 10-8) and a 5' downstream CNPY2
      variant (rs10783780; P = 3.33 * 10-7) on chromosome 12. Individuals heterozygous
      for GA*rs10492374 showed an increased expression of the OVCH1 gene. The
      rs10783780 genotypes were not associated with CNPY2 mRNA levels, but the MG
      HLA*08:01 patients present a lower expression of this gene than the healthy
      controls. CONCLUSION: Our results showed that when we control for the influence
      of the ancestral haplotype 8.1, no polymorphism was demonstrated to be associated
      with EOMG development within the MHC region suggesting that the HLA-B*08:01
      allele is the unique genetic factor within the HLA region responsible for EOMG
      development in patients who carry the ancestral haplotype 8.1. Our study also
      identified two novel polymorphisms as risk factors for MG HLA-B*08:01 positive
      patients which regulate the expression of the OVCH1 and CNYP2 genes.

PMID- 29037441
TI  - Impact of ankle foot orthosis stiffness on Achilles tendon and gastrocnemius
      function during unimpaired gait.
AB  - Ankle foot orthoses (AFOs) are designed to improve gait for individuals with
      neuromuscular conditions and have also been used to reduce energy costs of
      walking for unimpaired individuals. AFOs influence joint motion and metabolic
      cost, but how they impact muscle function remains unclear. This study
      investigated the impact of different stiffness AFOs on medial gastrocnemius
      muscle (MG) and Achilles tendon (AT) function during two walking speeds. We
      performed gait analyses for eight unimpaired individuals. Each individual walked
      at slow and very slow speeds with a 3D printed AFO with no resistance (free hinge
      condition) and four levels of ankle dorsiflexion stiffness: 0.25Nm/ degrees ,
      1Nm/ degrees , 2Nm/ degrees , and 3.7Nm/ degrees . Motion capture, ultrasound,
      and musculoskeletal modeling were used to quantify MG and AT lengths with each
      AFO condition. Increasing AFO stiffness increased peak AFO dorsiflexion moment
      with decreased peak knee extension and peak ankle dorsiflexion angles. Overall
      musculotendon length and peak AT length decreased, while peak MG length increased
      with increasing AFO stiffness. Peak MG activity, length, and velocity
      significantly decreased with slower walking speed. This study provides
      experimental evidence of the impact of AFO stiffness and walking speed on joint
      kinematics and musculotendon function. These methods can provide insight to
      improve AFO designs and optimize musculotendon function for rehabilitation,
      performance, or other goals.

PMID- 29037439
TI  - Caenorhabditis elegans Dosage Compensation: Insights into Condensin-Mediated Gene
      Regulation.
AB  - Recent work demonstrating the role of chromosome organization in transcriptional
      regulation has sparked substantial interest in the molecular mechanisms that
      control chromosome structure. Condensin, an evolutionarily conserved multisubunit
      protein complex, is essential for chromosome condensation during cell division
      and functions in regulating gene expression during interphase. In Caenorhabditis
      elegans, a specialized condensin forms the core of the dosage compensation
      complex (DCC), which specifically binds to and represses transcription from the
      hermaphrodite X chromosomes. DCC serves as a clear paradigm for addressing how
      condensins target large chromosomal domains and how they function to regulate
      chromosome structure and transcription. Here, we discuss recent research on C.
      elegans DCC in the context of canonical condensin mechanisms as have been studied
      in various organisms.

PMID- 29037442
TI  - Estimation of in vivo inter-vertebral loading during motion using fluoroscopic
      and magnetic resonance image informed finite element models.
AB  - Finite element (FE) models driven by medical image data can be used to estimate
      subject-specific spinal biomechanics. This study aimed to combine magnetic
      resonance (MR) imaging and quantitative fluoroscopy (QF) in subject-specific FE
      models of upright standing, flexion and extension. Supine MR images of the lumbar
      spine were acquired from healthy participants using a 0.5 T MR scanner. Nine 3D
      quasi-static linear FE models of L3 to L5 were created with an elastic nucleus
      and orthotropic annulus. QF data was acquired from the same participants who
      performed trunk flexion to 60 degrees  and trunk extension to 20 degrees . The
      displacements and rotations of the vertebrae were calculated and applied to the
      FE model. Stresses were averaged across the nucleus region and transformed to the
      disc co-ordinate system (S1 = mediolateral, S2 = anteroposterior, S3 = axial). In
      upright standing S3 was predicted to be -0.7 +/- 0.6 MPa (L3L4) and -0.6 +/- 0.5
      MPa (L4L5). S3 increased to -2.0 +/- 1.3 MPa (L3L4) and -1.2 +/- 0.6 MPa (L4L5)
      in full flexion and to -1.1 +/- 0.8 MPa (L3L4) and -0.7 +/- 0.5 MPa (L4L5) in
      full extension. S1 and S2 followed similar patterns; shear was small apart from
      S23. Disc stresses correlated to disc orientation and wedging. The results
      demonstrate that MR and QF data can be combined in a participant-specific FE
      model to investigate spinal biomechanics in vivo and that predicted stresses are
      within ranges reported in the literature.

PMID- 29037443
TI  - A comprehensive assessment of the musculoskeletal system: The CAMS-Knee data set.
AB  - Combined knowledge of the functional kinematics and kinetics of the human body is
      critical for understanding a wide range of biomechanical processes including
      musculoskeletal adaptation, injury mechanics, and orthopaedic treatment outcome,
      but also for validation of musculoskeletal models. Until now, however, no
      datasets that include internal loading conditions (kinetics), synchronized with
      advanced kinematic analyses in multiple subjects have been available. Our goal
      was to provide such datasets and thereby foster a new understanding of how in
      vivo knee joint movement and contact forces are interlinked - and thereby impact
      biomechanical interpretation of any new knee replacement design. In this
      collaborative study, we have created unique kinematic and kinetic datasets of the
      lower limb musculoskeletal system for worldwide dissemination by assessing a
      unique cohort of 6 subjects with instrumented knee implants (Charite -
      Universitatsmedizin Berlin) synchronized with a moving fluoroscope (ETH Zurich)
      and other measurement techniques (including whole body kinematics, ground
      reaction forces, video data, and electromyography data) for multiple complete
      cycles of 5 activities of daily living. Maximal tibio-femoral joint contact
      forces during walking (mean peak 2.74 BW), sit-to-stand (2.73 BW), stand-to-sit
      (2.57 BW), squats (2.64 BW), stair descent (3.38 BW), and ramp descent (3.39 BW)
      were observed. Internal rotation of the tibia ranged from 3 degrees  external to
      9.3 degrees  internal. The greatest range of anterio-posterior translation was
      measured during stair descent (medial 9.3 +/- 1.0 mm, lateral 7.5 +/- 1.6 mm),
      and the lowest during stand-to-sit (medial 4.5 +/- 1.1 mm, lateral 3.7 +/- 1.4
      mm). The complete and comprehensive datasets will soon be made available online
      for public use in biomechanical and orthopaedic research and development.

PMID- 29037444
TI  - Prevalence and Prognostic Relevance of Ventricular Conduction Disturbances in
      Patients With Aortic Stenosis.
AB  - The prevalence and prognostic implications of ventricular conduction disturbances
      in aortic stenosis (AS) have not been extensively evaluated. The present
      retrospective study investigated the prevalence and prognostic implications of
      ventricular conduction abnormalities (including the QRS morphology and duration)
      in AS. A total of 1,245 patients (mean age 66 +/- 14 years, 62.8% men) with
      varying AS severity (aortic sclerosis 33.9%, mild AS 11.5%, moderate AS 29.9%,
      and severe AS 24.7%) were evaluated. Demographic, clinical variables, and
      presence of ventricular conduction abnormalities on the electrocardiogram (based
      on QRS morphology and duration) were related to occurrence of all-cause
      mortality, correcting for occurrence of aortic valve replacement. The prevalence
      of ventricular conduction disorders increased in parallel with AS severity, which
      was particularly significant for left bundle branch block (4.3% in aortic
      sclerosis, 2.1% in mild AS, 4.6% in moderate AS, and 8.1% in severe AS; p =
      0.042). The QRS duration showed a slight prolongation with increasing AS severity
      (102 +/- 21 ms in aortic valve sclerosis, 99 +/- 18 ms in mild AS, 104 +/- 22 ms
      in moderate AS, and 105 +/- 22 ms in severe AS; p = 0.044). During a mean follow
      up of 8.1 +/- 4.8 years, 40.9% of patients died. Right bundle branch block
      morphology (hazard ratio 1.59, 95% confidence interval 1.18 to 2.13, p = 0.002)
      and increase of QRS duration (hazard ratio 1.06, 95% confidence interval 1.02 to
      1.11; p = 0.006) were independently associated with all-cause mortality. In
      conclusion, ventricular conduction disorders became more prevalent with
      increasing severity of AS and have an impact on survival.

PMID- 29037445
TI  - Effect of Age and Renal Function on Survival After Left Ventricular Assist Device
      Implantation.
AB  - Left ventricular assist devices (LVAD) are increasingly used, especially as
      destination therapy in in older patients. The aim of this study was to evaluate
      the effect of age on renal function and mortality in the first year after
      implantation. A retrospective multicenter cohort study was conducted, evaluating
      all LVAD patients implanted in the 2 participating centers (age >=18 years).
      Patients were stratified according to the age groups <45, 45-54, 55-64, and >=65
      years old. Overall, 241 patients were included (mean age 52.4 +/- 12.9 years, 76%
      males, 33% destination therapy). The mean estimated Glomerular Filtration Rate
      (eGFR) at 1 year was 85, 72, 69, and 49 mL/min per 1.73 m2 in the age groups
      <45(n = 65, 27%), 45-54(n = 52, 22%), 55-64(n = 87, 36%), and >=65 years (n = 37,
      15%) p <0.001)), respectively. Older age and lower eGFR at baseline (p <0.01)
      were independent predictors of worse renal function at 1 year. The 1-year
      survival post-implantation was 79%,84%, 68%, and 54% for those in the age group
      <45, 45-54, 55-64 and >=65 years (Log-rank p = 0.003). Older age, lower eGFR and,
      INTERMACS class I were independent predictors of 1-year mortality. Furthermore,
      older patients (age > 60 years) with an impaired renal function (eGFR <55 mL/min
      per 1.73 m2) had a 5-fold increased hazard ratio for mortality during the first
      year after implantation (p <0.001). In conclusion, age >60 years is an
      independent predictor for an impaired renal function and mortality. Older age
      combined with reduced renal function pre-implantation had a cumulative adverse
      effect on survival in patients receiving a LVAD.

PMID- 29037446
TI  - Transcatheter Aortic Valve Implantation Futility Risk Model Development and
      Validation Among Treated Patients With Aortic Stenosis.
AB  - Risk-benefit assessment for transcatheter aortic valve implantation (TAVI) is
      still evolving. A sizeable group of patients do not fully benefit from
      intervention despite a technically successful procedure. All patients who
      underwent TAVI with device success and with no Valve Academic Research Consortium
      (VARC)-2 defined complications were included. Various demographic data, clinical
      details, and echocardiographic findings were examined. The outcome was defined as
      1-year composite of mortality, stroke, lack of functional-class improvement (by
      New York Heart Association class), and readmissions (>=1 month after the
      procedure). Logistic regression was used to fit the prediction model. We used a
      10-fold cross-validation to validate our results. Of 543 patients, 435 met the
      inclusion criteria. The mean age was 82 (+/-6.5) years, 43% were men, and the
      mean Society of Thoracic Surgeons score was 6.6 (+/-4.7). At 1 year, 66 of 435
      patients (15%) experienced the study end point. The final logistic regression
      model included diabetes, baseline New York Heart Association functional class,
      diastolic dysfunction, need for diuretics, mean gradient, hemoglobin level, and
      creatinine level. The area under the curve was 0.73 and was reduced to 0.71 after
      validation, with a 97% specificity using a single cutoff. Dividing to low-,
      medium-, and high-risk groups for futility produced a corresponding prevalence of
      6%, 19%, and 59% futility. A web application for the prediction model was
      developed and provided. In conclusion, this prediction score may provide an
      important insight and may facilitate identification of patients who, despite a
      technically successful and uncomplicated procedure, have risk that may outweigh
      the benefit of a contemplated TAVI.

PMID- 29037447
TI  - A quinidine non responsive novel KCNT1 mutation in an Indian infant with epilepsy
      of infancy with migrating focal seizures.
AB  - Epilepsy of infancy with migrating focal seizures {a.k.a malignant migrating
      partial seizures of infancy (MMPSI)} is an uncommon epileptic encephalopathy with
      a poor prognosis. Migrating focal seizures with autonomic features, developmental
      stagnation and refractoriness to treatment are its key features. It is caused by
      genetic defects in various ion channels, most common being sodium activated
      potassium channel (KCNT1), found in up to 50% of cases. With advent of genetic
      diagnosis and precision medicine, many targeted therapies have been identified.
      Antagonist of KCNT1 coded ion channel like Quinidine has shown promising results
      in MMPSI. Here we report first mutation proven case of MMPSI from India. This
      child had a novel heterozygous missense mutation in exon10 of the KCNT1 gene
      (chr9:138650308; c.808C > C/G (p.Q270E)) which was pathogenic. Neither quinidine
      nor ketogenic diet could control his seizures. Ultimately, the child succumbed to
      his illness at nine months of age.

PMID- 29037449
TI  - Open thoracostomy as treatment of chronic empyema with bronchopleural fistula.

PMID- 29037448
TI  - Effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition with
      Bococizumab on Lipoprotein Particles in Hypercholesterolemic Subjects.
AB  - PURPOSE: Monoclonal antibody inhibitors of proprotein convertase subtilisin/kexin
      type 9 (PCSK9) elicit significant reductions in serum LDL-C levels. However,
      little is known about their effects on lipoprotein particles. The purpose of this
      analysis was to evaluate the effect of PCSK9 inhibition with bococizumab
      (RN316/PF-04950615), a humanized monoclonal antibody to PCSK9, on LDL, VLDL, and
      HDL particle concentration and size in hypercholesterolemic subjects. METHODS:
      Data from 3 double-blind, placebo-controlled, randomized studies were analyzed.
      In study 1, a total of 67 hypercholesterolemic subjects received IV placebo or
      bococizumab 0.25, 0.5, 1, or 1.5 mg/kg weekly for 4 weeks. In studies 2 and 3, a
      total of 135 hypercholesterolemic subjects taking statins received IV placebo or
      bococizumab 0.25, 1, 3, or 6 mg/kg monthly for 12 weeks. Lipoprotein particle
      concentration and size were measured by using nuclear magnetic resonance
      spectroscopy. FINDINGS: Overall, the majority of subjects were men (51.9%) aged
      >50 years of age and of white ethnic origin. In total, 189 subjects with both
      baseline and 2-week posttreatment data were included in the analysis. After PCSK9
      inhibition with bococizumab 0.5, 1, 1.5, 3, and 6 mg/kg, concentrations of total
      LDL, total small LDL, and small VLDL particles decreased significantly versus
      baseline and placebo (P < 0.05), whereas concentrations of HDL particles
      increased (P < 0.05). The size of the LDL, VLDL, and HDL particles increased
      after PCSK9 inhibition. Reductions in LDL-C and total LDL particle concentrations
      were highly correlated. IMPLICATIONS: The effect of inhibiting PCSK9 with
      bococizumab on lipoprotein particle concentration and size are consistent with
      the general mechanism of PCSK9 inhibitors in blocking PCSK9-mediated
      downregulation of LDL receptors. PCSK9 inhibition has the potential to provide a
      clinical benefit through the modulation of atherogenic lipoprotein particles in
      addition to LDL-C lowering, and this effect will likely be assessed in future
      analyses of data from cardiovascular outcomes trials of PCSK9 monoclonal
      antibodies that are currently being conducted. ClinicalTrials.gov identifiers:
      NCT01243151, NCT01342211, and NCT01350141.

PMID- 29037450
TI  - Tissue expression of tubular injury markers is associated with renal function
      decline in diabetic nephropathy.
AB  - AIMS: The pathogenesis of diabetic kidney disease (DKD) is complex and
      multifactorial; increasing evidence suggests that tubular injury and inflammatory
      process are involved in disease progression. We investigated the potential
      association of renal expression of tubular injury markers, neutrophil gelatinase
      associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and inflammatory
      markers, tumor necrosis factor receptor (TNFR) 1 and 2 with renal progression in
      pathologically proven diabetic nephropathy (DN). METHODS: We identified 122
      patients with confirmed DN. After excluding patients with other coexisting renal
      disease or estimated glomerular filtration rate (eGFR) <30mL/min/1.73m2, 35
      patients were included. Annual decline of (GFR decline slope) was calculated
      using linear regression analysis. Tissue tubular and glomerular expressions of
      NGAL, KIM-1, TNFR1, and TNFR2 were assessed using immunohistochemistry. RESULTS:
      Median baseline urinary protein to creatinine ratio (uPCR) was 6.76 (2.18-7.61)
      mg/mg Cr, median baseline eGFR was 50 (43-66) mL/min per 1.73m2, and median GFR
      decline slope was 15.6 (4.4-35.1) mL/min per 1.73m2 per year. Positive
      correlations were observed between tubular expressions of NGAL and KIM-1, and GFR
      decline slopes (r=0.601, p<0.001; r=0.516, p=0.001, respectively), and between
      tubular expressions of KIM-1 and uPCR (r=0.596, p<0.001), and between NGAL and
      interstitial fibrosis and tubular atrophy (IFTA) score (r=0.391, p=0.024). No
      correlations were found between glomerular or tubular expressions of TNFRs, and
      clinical parameters including GFR decline slopes. On multivariate analysis, the
      association between tubular expressions of KIM-1 and GFR decline slopes was
      dependent on uPCR. Tubular expressions of NGAL were independently associated with
      GFR decline slopes, with an adjusted coefficient factor of 0.290 (95% confidence
      interval, 0.009-0.202, p=0.038). CONCLUSIONS: These findings suggest that tubular
      injury plays a key role in the pathogenesis of DKD in high-risk patients. Further
      studies are warranted to determine whether tubular injury could be a therapeutic
      target in DKD.

PMID- 29037451
TI  - [City-hospital network and quality control of officinal preparations].
AB  - OBJECTIVES: In a hospital environment, the quality control of the hospital
      preparations allows to release homogeneous batches in a secure way. These
      controls are totally integrated into the process of production and can also, in
      certain cases, be realized for high-alert magistral preparations. In community
      pharmacy, these controls were not required, but the Agence regionale de sante
      (ARS) recently incited compounding community pharmacies to realize this type of
      analyses. This decision motivated the creation of a collaboration between the
      pharmacy department of a French teaching hospital and a society including around
      thirty community pharmacies having a preparatory. METHODS: Twenty community
      pharmacies distributed on all the territory have submitted one of their pediatric
      preparation, capsules of captopril 2mg, to the pharmacopoeia controls usually
      realized in the industry or hospital. RESULTS: All the analyzed batches were in
      agreement with European Pharmacopeia specifications. CONCLUSIONS: We shall
      present the rational of this work, the results as well as the numerous
      perspectives offered by this new type of collaboration joining completely the
      logic of a network city-hospital allowing the improvement of security of the
      medication circuit in France.

PMID- 29037452
TI  - Balancing Immunity and Yield in Crop Plants.
AB  - Crop diseases cause enormous yield losses and threaten global food[ED1] security.
      The use of highly resistant cultivars can effectively control plant diseases, but
      in crops, genetic immunity to disease often comes with an unintended reduction in
      growth and yield. Here, we review recent advances in understanding how nucleotide
      binding domain, leucine-rich repeat (NLR) receptors and cell wall-associated
      kinase (WAK) proteins function in balancing immunity and yield. We also discuss
      the role of plant hormones and transcription factors in regulating the trade-offs
      between plant growth and immunity. Finally, we describe how a novel mechanism of
      translational control of defense proteins can enhance immunity without the
      reduction in fitness.

PMID- 29037453
TI  - Establishment of calculated panel reactive antibody and its potential benefits in
      improving the kidney allocation strategy in Taiwan.
AB  - BACKGROUND/PURPOSE: Renal transplant candidates who are highly sensitized to
      human leukocyte antigens (HLAs) tend to wait longer to find a matched donor and
      have poor outcomes. Most organ-sharing programs prioritize highly sensitized
      patients in the allocation scoring system. The HLA sensitization status is
      traditionally evaluated by the panel-reactive antibody (PRA) assay. However, this
      assay is method dependent and does not consider the ethnic differences in HLA
      frequencies. A calculated PRA (cPRA), based on a population's HLA frequency and
      patients' unacceptable antigens (UAs), correctly estimates the percentage of
      donors suitable for candidates. The Taiwan Organ Registry and Sharing Center does
      not prioritize sensitized patients. We propose that the incorporation of the cPRA
      and UAs into the renal allocation program will improve the local kidney
      allocation policy. METHODS: We established a cPRA calculator using 6146 Taiwanese
      HLA-A, -B, -C, -DR, and -DQ phenotypes. We performed simulated allocation based
      on the concept of acceptable mismatch for 76 candidates with cPRA values
      exceeding 80%. RESULTS: We analyzed 138 waitlisted renal transplant candidates at
      our hospital, and we determined that the concordance rate of the cPRA and PRA for
      highly sensitized (%PRA > 80%) candidates was 92.5%, which decreased to 20% for
      those with %PRA < 80%. We matched 76 highly sensitized patients based on
      acceptable mismatch with the HLA phenotypes of 93 cadaver donors. Forty-six
      patients (61%) found at least one suitable donor. CONCLUSION: The application of
      the cPRA and acceptable mismatch can benefit highly sensitized patients and
      reduce positive lymphocyte cytotoxicity crossmatch.

PMID- 29037454
TI  - Incidence of pertussis in subjects aged 50years and older in France in 2013-2014.
AB  - OBJECTIVE: To assess the incidence of pertussis (whooping cough) in subjects aged
      50years and older in France. METHODS: Participating family physicians (FPs) using
      the patient record management software AxiSante(r) included patients aged 50years
      and older, who had signed an informed consent form, presenting with persistent
      cough for 7 to 21days. Bordetella genetic material was detected by polymerase
      chain reaction (PCR) on nasopharyngeal samples collected at the FP's discretion.
      RESULTS: A total of 42 FPs included 129 patients from June 2013 to August 2014
      (large cities: 38; medium-sized cities: 57; rural areas: 34); 106 samples were
      analyzed. Overall, 30 pertussis cases were diagnosed: 10 cases confirmed by PCR,
      18 purely clinical cases, and two direct epidemiological cases. The crude
      incidence rate per 100,000 patients aged>=50years was 103.6 (95% CI: 69.9-47.9):
      77.1 in large cities, 103.1 in medium-sized cities, and 143.9 in rural areas. The
      extrapolated incidence rate per 100,000 persons aged>=50years was 187.1 (95% CI:
      126.2-67.1): 131.1 in large cities, 256.1 in medium-sized cities, and 242.2 in
      rural areas. CONCLUSION: The population aged 50years and older can serve as a
      reservoir. Its role in Bordetella pertussis circulation should be taken into
      account for pertussis booster vaccination programs.

PMID- 29037456
TI  - Factual Inaccuracies Contained in the Article Entitled, "Low Yield of Mobile
      Cardiac Outpatient Telemetry after Cryptogenic Stroke in Patients with Extensive
      Cardiac Imaging".

PMID- 29037455
TI  - Role-emerging placements (REPs) - An evolving alternative for student pharmacist
      experiential education.

PMID- 29037457
TI  - Epidemiology and burden of HPV-related disease.
AB  - Human papillomavirus (HPV) infection is recognized as one of the major causes of
      infection-related cancer in both men and women. High-risk HPV types are not only
      responsible for virtually all cervical cancer cases but also for a fraction of
      cancers of the vulva, vagina, penis, anus, and head and neck cancers.
      Furthermore, HPV is also the cause of anogenital warts and recurrent respiratory
      papillomatosis. Despite the availability of multiple preventative strategies, HPV
      related cancer remains a leading cause of morbi-mortality in many parts of the
      world, particularly in less developed countries. Thus, in this review, we
      summarize the latest estimates of the global burden of HPV-related diseases,
      trends, the attributable fraction by HPV types, and the potential preventative
      fraction.

PMID- 29037458
TI  - A new large species of gecko of the genus Hemidactylus Oken, 1817 (Reptilia:
      Sauria: Gekkonidae) from the Eastern Ghats, India.
AB  - A new large species of gecko superficially resembling Hemidactylus maculatus
      Dumeril & Bibron and its allied large Hemidactylus is described from Eastern
      Ghats. The new species, Hemidactylus kangerensis sp. nov. can be easily
      distinguished from members of the H. maculatus complex based on the number of
      femoral pores, i.e. 18-21 on each side, separated medially by 4 non-pored scales.
      A phylogenetic analysis based on partial sequence of mitochondrial gene
      cytochrome b shows that the gecko is a member of the "H. prashadi" clade and is
      sister to H. maculatus, from which it differs in an uncorrected pairwise sequence
      divergence of 10%. The discovery of a new large gecko from Eastern Ghats
      advocates the need for biodiversity assessment across the neglected Eastern
      Ghats.

PMID- 29037459
TI  - Undisciplined Thinking Facilitates Accessible Writing: A Response to Doubleday
      and Connell.

PMID- 29037460
TI  - Creativity: The Stronger, Blacker Sheep behind Great Papers - A Reply to
      Falkenberg and Tubb.

PMID- 29037461
TI  - Sustained improvement in vancomycin dosing and monitoring post-implementation of
      guidelines: Results of a three-year follow-up after a multifaceted intervention
      in an Australian teaching hospital.
AB  - INTRODUCTION: Despite vancomycin being in use for over half-a-century, it is
      still not dosed or monitored appropriately in many centers around the world. The
      objective of this study was to determine the effectiveness of a multifaceted
      intervention to implement a vancomycin dosing and monitoring guideline across
      multiple medical and surgical units over time. METHODS: This was an observational
      before-and-after interventional cohort study. The pre-intervention period was
      August to December 2010-2011 and the post-intervention period was September to
      November 2012-2014. The implementation strategy comprised: face-to-face
      education, online continuing medical education, dissemination of pocket guideline
      and email reminder. Outcome measures included: appropriate prescribing of loading
      and maintenance doses, therapeutic drug monitoring, time to attain target range
      and nephrotoxicity. RESULTS: Post-implementation prescribing of loading doses
      increased (10.4%-43.6%, P=<0.001), guideline adherent first maintenance dose (44%
      68.4% P = 0.04), correct dose adjustment from (53.1%-72.2%, P = 0.009).
      Beneficial effects pre and post-implementation were observed for adherent timing
      of initial concentration (43.2%-51.9%, P = 0.01), concentrations in target range
      (32.6%-44.1%, P = 0.001), time to target range (median 6-4 days, P=<0.001),
      potentially nephrotoxic concentrations (30.7%-20.9%, P=<0.001) and nephrotoxicity
      (10.4%-6.8%, P=<0.001). CONCLUSIONS: A multifaceted intervention to implement a
      vancomycin dosing and monitoring guideline significantly improved prescribing,
      monitoring, pharmacokinetic and safety outcomes for patients treated with
      vancomycin over an extended period. However, increased guideline adoption by
      clinicians is required to maximize and prolong the utility of this important
      agent.

PMID- 29037462
TI  - Suicide in Castellon, 2009-2015: Do sociodemographic and psychiatric factors help
      understand urban-rural differences?
AB  - INTRODUCTION: Studies have pointed to rurality as an important factor influencing
      suicide. Research so far suggests that several sociodemograpic and psychiatric
      factors might influence urban-rural differences in suicide. Also, their
      contribution appears to depend on sex and age. Unfortunately, studies including a
      comprehensive set of explanatory variables altogether are still scare and most
      studies have failed to present their analyses split by sex and age groups. Also,
      urban-rural differences in suicide in Spain have been rarely investigated. The
      present study aimed at explaining rural-urban differences in suicidality in the
      province of Castellon (Spain). A comprehensive set of sociodemographic and
      psychiatric factors was investigated and analyses were split by sex and age.
      MATERIAL AND METHOD: The sample comprised all suicides recorded in the province
      of Castellon from January 2009 to December 2015 (n=343). Sociodemographic data
      included sex, age, and suicide method. Psychiatric data included the history of
      mental health service utilization, psychiatric diagnosis, suicide attempts, and
      psychiatric hospitalization. RESULTS: Consistent with past research, suicide
      rates were highest in rural areas, especially in men and older people. We also
      found that urban-rural differences in sociodemographic and psychiatric variables
      were sensitive to sex and age. Our results indicated that specialized mental
      health service use and accessibility to suicide means might help understand urban
      rural differences in suicide, especially in men. When exploring urban-rural
      differences as a function of age, general practitioner visits for psychiatric
      reasons were more frequent in the older age group in rural areas. CONCLUSIONS:
      Study implications for suicide prevention strategies in Spain are discussed.

PMID- 29037464
TI  - [Ocular sarcoidosis: What the internist should know?]
AB  - Sarcoidosis is one of the leading causes of inflammatory eye disease. Any part of
      the eye and its adnexal tissues can be involved. Uveitis and optic neuropathy are
      the main manifestations, which the internists face. This review reports the state
      of knowledge for these two ocular involvements and proposes an assessment
      algorithm for sarcoidosis in patients with suspected sarcoid uveitis. Two groups
      of patients with sarcoid uveitis can be distinguished: one young and multiethnic
      group in which ophthalmological findings are various and another group of elderly
      Caucasian women with mostly chronic posterior uveitis. Clinically isolated
      uveitis revealing sarcoidosis remains a strictly ocular condition in a large
      majority of cases. Although it could be a serious condition involving functional
      prognosis, an early recognition in addition to a growing therapeutic arsenal
      including intravitreal implant seems to have improved visual prognosis of the
      disease in the last years. Systemic corticosteroids are indicated when uveitis
      does not respond to topical corticosteroids or when there is bilateral posterior
      involvement, especially macular edema and occlusive vasculitis. In up to 25% of
      cases that require an unacceptable dosage of corticosteroids to maintain
      remission, additional immunosuppression is used, including methotrexate,
      azathioprine, and mycophenolate mofetil. Regarding systemic sarcoidosis,
      infliximab and adalimumab have been successfully used for the treatment of
      refractory or sight-threatening disease. Optic neuropathy often affects women of
      African and Caribbean origin. Some authors recommend that patients be treated
      with high-dose corticosteroids and concurrent immunosuppression from the onset
      for this manifestation, which may be associated with a poorer outcome.

PMID- 29037465
TI  - Influence of exposure time on the release of bacteria from a biofilm on Ti6Al4V
      discs using sonication: An in vitro model.
AB  - Implant sonication is considered a useful method for the diagnosis of implant
      related infections. We designed an in vitro study using Ti6Al4V discs and 5
      different bacteria to determine the optimal sonication time for recovery of most
      bacteria tested to enable use of sonication in clinical practice for
      microbiological diagnosis of implant-related infections. We carried out a
      specific protocol for the adherence and subsequent biofilm formation on the
      materials used. The discs were then sonicated and the retrieved bacteria were
      quantified. From minute 1 to 5, the amount of recovered organisms grew
      progressively for all bacteria. Between minute 6 and minute 10, the number was
      irregular for all strains except E. coli, though no pattern was evidenced. E.
      coli was the only microorganism with a progressive increase in liberation
      throughout the process. Significant differences were observed in each of the
      10minutes analyzed as concerns the release of the 5 strains (P<0.021) as well as
      in the mean dislodgement (of the 10minutes) of all tested strains (P<0.00001).
      Considering that infections in which biofilms are involved could be
      polymicrobial, we concluded that 5minutes is the optimal time of sonication in
      order to recover the maximum amount of most bacteria attached to Ti6Al4V discs.

PMID- 29037466
TI  - The Use of a GroEL-BLI Biosensor to Rapidly Assess Preaggregate Populations for
      Antibody Solutions Exhibiting Different Stability Profiles.
AB  - An automated method using biotinylated GroEL-streptavidin biosensors with
      biolayer interferometry (GroEL-BLI) was evaluated to detect the formation of
      transiently formed, preaggregate species in various pharmaceutically relevant
      monoclonal antibody (mAb) samples. The relative aggregation propensity of various
      IgG1 and IgG4 mAbs was rank ordered using the GroEL-BLI biosensor method, and the
      least stable IgG4 mAb was subjected to different stresses including elevated
      temperatures, acidic pH, and addition of guanidine HCl. The GroEL-BLI biosensor
      detects mAb preaggregate formation mostly before, or sometimes concomitantly
      with, observing soluble aggregates and subvisible particles using size-exclusion
      chromatography and microflow imaging, respectively. A relatively unstable
      bispecific antibody (Bis-3) was shown to bind the GroEL biosensor even at low
      temperatures (25 degrees C). During thermal stress (50 degrees C, 1 h), increased
      Bis-3 binding to GroEL-biosensors was observed prior to aggregation by size
      exclusion chromatography or microflow imaging. Transmission electron microscopy
      analysis of Bis-3 preaggregate GroEL complexes revealed, in some cases, potential
      hydrophobic interaction sites between the Fc domain of the Bis-3 and GroEL
      protein. The automated BLI method not only enables detection of transiently
      formed preaggregate species that initiate protein aggregation pathways but also
      permits rapid mAb formulation stability assessments at low volumes and low
      protein concentrations.

PMID- 29037467
TI  - Cross cultural adaptation and refinement of an English version of a Dutch patient
      reported questionnaire for hand sensitivity: The Radboud Evaluation of
      Sensitivity.
AB  - STUDY DESIGN: Longitudinal clinical measurement. INTRODUCTION: Sensory
      alterations in the hand can present as both decreased sensation or numbness, and
      hyperesthesia, including mechanical allodynia and cold intolerance. However, few
      patient-reported outcomes have been developed and validated for evaluation,
      particularly for increased sensitivity. The Radboud Evaluation of Sensitivity was
      developed in the Netherlands for patient-reported evaluation of hand sensitivity
      in complex regional pain syndrome. PURPOSE OF THE STUDY: The purpose of this
      study was to translate into English and culturally validate the Radboud
      Evaluation of Sensitivity for the North American context. METHODS: Forward and
      backward translation, followed by a psychometric evaluation of the synthesized
      version of the translated tool, was undertaken in a heterogeneous group of
      persons after hand injury, including nerve injuries, hand trauma, and complex
      regional pain syndrome. RESULTS: Thirty-six persons completed test-retest
      reliability testing, yielding an intraclass correlation coefficient of 0.92 (95%
      CI 0.85 to 0.96) for single measures. Internal consistency was also high at alpha
      = 0.96 in a larger sample (n = 56). Although some support for construct validity
      was generated, several validity hypotheses were not confirmed. Of interest, there
      appeared to be significant differences in the scores between persons with
      hypoesthesia as compared with those with hyperesthesia. CONCLUSIONS: The Radboud
      Evaluation of Sensitivity, English version appears to be a reliable tool for the
      self-reported evaluation of sensory alterations in the hand, including both
      hypoesthesia and hyperesthesia. More research is needed to add to the extent of
      and confidence in the validity and responsiveness of this assessment. LEVEL OF
      EVIDENCE: Level II.

PMID- 29037463
TI  - In vivo bone strain and finite element modeling of a rhesus macaque mandible
      during mastication.
AB  - Finite element analysis (FEA) is a commonly used tool in musculoskeletal
      biomechanics and vertebrate paleontology. The accuracy and precision of finite
      element models (FEMs) are reliant on accurate data on bone geometry, muscle
      forces, boundary conditions and tissue material properties. Simplified modeling
      assumptions, due to lack of in vivo experimental data on material properties and
      muscle activation patterns, may introduce analytical errors in analyses where
      quantitative accuracy is critical for obtaining rigorous results. A subject
      specific FEM of a rhesus macaque mandible was constructed, loaded and validated
      using in vivo data from the same animal. In developing the model, we assessed the
      impact on model behavior of variation in (i) material properties of the
      mandibular trabecular bone tissue and teeth; (ii) constraints at the
      temporomandibular joint and bite point; and (iii) the timing of the muscle
      activity used to estimate the external forces acting on the model. The best match
      between the FEA simulation and the in vivo experimental data resulted from
      modeling the trabecular tissue with an isotropic and homogeneous Young's modulus
      and Poisson's value of 10GPa and 0.3, respectively; constraining translations
      along X,Y, Z axes in the chewing (left) side temporomandibular joint, the
      premolars and the m1; constraining the balancing (right) side temporomandibular
      joint in the anterior-posterior and superior-inferior axes, and using the muscle
      force estimated at time of maximum strain magnitude in the lower lateral gauge.
      The relative strain magnitudes in this model were similar to those recorded in
      vivo for all strain locations. More detailed analyses of mandibular strain
      patterns during the power stroke at different times in the chewing cycle are
      needed.

PMID- 29037468
TI  - Insights Into the Pathophysiology of Esophageal Adenocarcinoma.
AB  - Although researchers have identified genetic alterations that contribute to
      development of esophageal adenocarcinoma, we know little about features of
      patients or environmental factors that mediate progression of chronic acid
      biliary reflux to Barrett's esophagus and cancer. Increasing our understanding of
      the mechanisms by which normal squamous epithelium progresses to early-stage
      invasive cancer will help formulate rational surveillance guidelines and allow us
      to divest resources away from patients at low risk of malignancy. We review the
      cellular and genetic alterations that occur during progression of Barrett's
      esophagus, based on findings from clinical studies and mouse models of disease.
      We review the features of the luminal and mucosal microenvironment of Barrett's
      esophagus that promote, in a small proportion of patients, development of
      esophageal adenocarcinoma. Markers of clonal evolution can be used to determine
      patient risk for cancer and set surveillance intervals.

PMID- 29037470
TI  - Pathophysiology of Gastroesophageal Reflux Disease.
AB  - The pathogenesis of gastroesophageal reflux disease (GERD) is complex and
      involves changes in reflux exposure, epithelial resistance, and visceral
      sensitivity. The gastric refluxate is a noxious material that injures the
      esophagus and elicits symptoms. Esophageal exposure to gastric refluxate is the
      primary determinant of disease severity. This exposure arises via compromise of
      the anti-reflux barrier and reduced ability of the esophagus to clear and buffer
      the refluxate, leading to reflux disease. However, complications and symptoms
      also occur in the context of normal reflux burden, when there is either poor
      epithelial resistance or increased visceral sensitivity. Reflux therefore
      develops via alterations in the balance of aggressive and defensive forces.

PMID- 29037469
TI  - Management of Patients With Adenocarcinoma or Squamous Cancer of the Esophagus.
AB  - Esophageal cancer is characterized by early and frequent metastasis. Surgery is
      the primary treatment for early-stage disease, whereas patients with patients
      with locally advanced disease receive perioperative chemotherapy or
      chemoradiotherapy. Squamous cancers can be treated with primary chemoradiotherapy
      without surgery, depending on their response to therapy and patient tolerance for
      subsequent surgery. Chemotherapy with a fluorinated pyrimidine and a platinum
      agent, followed by later treatment with taxanes and irinotecan, provides some
      benefit. Agents that inhibit the erb-b2 receptor tyrosine kinase 2 (ERBB2 or
      HER2), or vascular endothelial growth factor, including trastuzumab, ramucirumab,
      and apatinib, increase response and survival times. Esophageal adenocarcinomas
      have mutations in tumor protein p53 and mutations that activate receptor
      associated tyrosine kinase, vascular endothelial growth factor, and cell cycle
      pathways, whereas esophageal squamous tumors have a distinct set of mutations.
      Esophageal cancers develop systems to evade anti-tumor immune responses, but
      studies are needed to determine how immune checkpoint modification contributes to
      esophageal tumor development.

PMID- 29037471
TI  - A Behavioral Economic Approach to Improving Human Papillomavirus Vaccination.
AB  - PURPOSE: The objectives of this study were to measure the impact of a behavioral
      economic intervention on human papillomavirus (HPV) vaccine initiation and series
      completion rates for adolescents and to measure the impact of the intervention on
      the receipt of a nonincentivized influenza vaccine. METHODS: We conducted a quasi
      randomized trial to compare the impact of an escalating delayed cash incentive
      (intervention), compared with usual care (control), on HPV vaccination initiation
      and series completion rates among adolescents (11-17 years) at an urban medical
      center. We measured HPV vaccine initiation and completion rates during the 12
      months after enrollment and subsequent influenza vaccination rates for 24 months
      after enrollment. RESULTS: A total of 85 participants were actively enrolled in
      the intervention arm and 103 were passively enrolled in the control arm.
      Participants were predominantly publically insured African-American and Hispanic
      adolescents. The majority (75%) of the intervention group received one or more
      doses of the HPV vaccine, with 36% completing the three-dose series, compared
      with 47% of the control group receiving one or more doses and only 13% completing
      the series. The odds of HPV p-value vaccine initiation (odds ratio 4.19 [95%
      confidence interval 1.84-10.10], p < .01) and HPV vaccine series completion (OR
      4.16 [95% confidence interval 1.64-11.28], p < .01) were greater among the
      intervention group compared with the control group. There was no difference in
      influenza vaccination rates between the intervention group and the control group
      during the 2013-2014 season (p = .138) and during the 2014-2015 influenza season
      (p value .683). CONCLUSIONS: An incentive-based approach to HPV vaccination was
      effective in increasing vaccine initiation and series dose completion.

PMID- 29037472
TI  - Sample size estimation for cluster randomized controlled trials.
AB  - Cluster randomized controlled trials (cRCTs) are commonly used by clinical
      researchers. The advantages of cRCTs include preventing treatment contamination,
      enhancing administrative efficiency, convenience, external validity, ethical
      considerations, and likelihood of increased compliance by participants. However,
      when designing a cRCT, clinical researchers are faced with challenges, such as
      cluster units that may not have an equal number of participants within each. In
      this Technical Note, we discuss approaches for estimating the sample size, while
      taking into account unequal cluster sizes, and strategies for optimizing the
      design of cluster trials.

PMID- 29037474
TI  - Land surface phenology: What do we really 'see' from space?
AB  - Land surface phenology (LSP) provides bio-indication of ongoing climate change.
      It uses space-borne greenness proxies to monitor plant phenology at the landscape
      level from the regional to global scale. However, several unconsidered
      methodological and observational -related limitations may lead to
      misinterpretation of the satellite-derived signals. For instance, changes in
      species composition within a pixel could result in a change in the time series of
      the greenness proxy, due to the distinct phenology of the plant species involved.
      The change in the signal would then be misinterpreted as a phenological change
      while it is actually related to changes in species composition within the pixel.
      Other limitations include the selection of the smoothing technique and the method
      used to extract the LSP metrics. These not only may affect the timing of the LSP
      metrics but also the sign of the observed LSP change. Another and much less known
      limitation is related to the mixed signal from multi-canopy layers. Satellites
      may detect changes that corresponds to the understorey layer in complex vertical
      vegetation systems while the 'real' contribution of this layer (in terms of
      ecosystem functioning and dynamics) might be small compared to the undetected
      overstorey layer in cases of a late overstorey development. Here, some of the LSP
      basics are reviewed with emphasis on these (and other) potential sources of
      misinterpretation. Several aids to overcome these limitations, which include
      suggestions for multi methods analysis and the integration of information from
      satellite and ground-based sensors are provided alongside some prospective future
      LSP research directions.

PMID- 29037473
TI  - Ginsenoside Re protects against phencyclidine-induced behavioral changes and
      mitochondrial dysfunction via interactive modulation of glutathione peroxidase-1
      and NADPH oxidase in the dorsolateral cortex of mice.
AB  - We investigated whether ginsenoside Re (Re) modulates phencyclidine (PCP)-induced
      sociability deficits and recognition memory impairments to extend our recent
      finding. We examined the role of GPx-1 gene in the pharmacological activity of Re
      against mitochondrial dysfunction induced by PCP in the dorsolateral cortex of
      mice. Since mitochondrial oxidative stress activates NADPH oxidase (PHOX), we
      applied PHOX inhibitor apocynin for evaluating interactive modulation between GPx
      1 and PHOX against PCP neurotoxicity. Sociability deficits and recognition memory
      impairments induced by PCP were more pronounced in GPx-1 knockout (KO) than in
      wild type (WT) mice. PCP-induced mitochondrial oxidative stress, mitochondrial
      dysfunction, and membrane translocation of p47phox were more evident in GPx-1 KO
      than in WT. Re treatment significantly attenuated PCP-induced neurotoxic changes.
      Re also significantly attenuated PCP-induced sociability deficits and recognition
      memory impairments. The attenuation by Re was comparable to that by apocynin. The
      attenuation was more obvious in GPx-1 KO than in WT. Importantly, apocynin did
      not show any additional positive effects on the neuroprotective activity of Re,
      indicating that PHOX is a molecular target for therapeutic activity of Re. Our
      results suggest that Re requires interactive modulation between GPx activity and
      PHOX (p47phox) to exhibit neuroprotective potentials against PCP insult.

PMID- 29037475
TI  - Chronic arsenicosis and cadmium exposure in wild snowshoe hares (Lepus
      americanus) breeding near Yellowknife, Northwest Territories (Canada), part 1:
      Evaluation of oxidative stress, antioxidant activities and hepatic damage.
AB  - Previous gold mining activities and arsenopyrite ore roasting activities at the
      Giant mine site (1948 to 2004) resulted in the release of high amounts of arsenic
      and trace metals into the terrestrial and aquatic ecosystems of Yellowknife,
      Northwest Territories, Canada. While elevated levels of arsenic has been
      consistently reported in surface soils and vegetation near the vicinity of the
      Giant mine area and in surrounding locations, systematic studies evaluating the
      overall health status of terrestrial small mammals endemic to the area are
      lacking. The purpose of this present study was to evaluate and comparatively
      assess the biochemical responses and histopathological effects induced by chronic
      arsenic and cadmium exposure in wild snowshoe hares breeding near the city of
      Yellowknife, specifically around the vicinity of the abandoned Giant mine site
      and in reference locations. Analysis included measurement of total arsenic and
      cadmium concentration in nails, livers, kidneys, bones, stomach content of hares,
      in addition to histopathological evaluation of hepatic and ocular lesions.
      Biochemical responses were determined through measurement of lipid peroxidation
      levels and antioxidant enzymes activities (catalase, superoxide dismutase,
      glutathione peroxidase, and glutathione disulfide). The results revealed that
      arsenic concentration was 17.8 to 48.9 times higher in the stomach content, and
      in the range of 4 to 23 times elevated in the nails of hares from the mine area
      compared to the reference location. Arsenic and cadmium levels were also noted to
      be increased in the bones, renal and hepatic tissues of hares captured near the
      mine area compared to the reference site. Specifically, hares from the mine area
      showed nail cadmium levels that was 2.3 to 17.6 times higher than those from the
      reference site. Histopathological examination of the eyes revealed no specific
      ocular lesions, such as lens opacity (cataracts) or conjunctivitis; however,
      hares from both locations exhibited hepatic steatosis (fatty liver change). Lipid
      peroxidation levels were relatively increased and accompanied with reduced
      antioxidant enzyme activities in hares from the mine area compared to the hares
      from the reference site. The results of this preliminary study suggest that the
      snowshoe hares breeding near the vicinity of Yellowknife, including near the
      Giant mine area have been chronically exposed to elevated levels of arsenic and
      cadmium, which consequently led to the increased levels of oxidative stress and
      perturbation of antioxidant defense system in exposed animals. The results of
      this present study constitute the first observation of chronic arsenicosis in
      wild small mammal species in Canada.

PMID- 29037476
TI  - Zirconia-incorporated zinc oxide eugenol has improved mechanical properties and
      cytocompatibility with human dental pulp stem cells.
AB  - OBJECTIVE: Zinc oxide eugenol (ZOE) is widely used as a therapeutic dental
      restorative material. However, ZOE has poor mechanical properties and high
      cytotoxicity toward human dental pulp stem cells (hDPSCs) due to the release of
      Zn ions. In this study, zirconia-incorporated ZOE (ZZrOE) was developed to reduce
      the cytotoxicity and improve the mechanical properties of ZOE with sustained
      therapeutic effects on inflamed hDPSCs in terms of inflammatory gene expression
      levels compared with those of the original material. METHODS: After the setting
      time and mechanical properties of ZZrOE incorporating varying amounts of zirconia
      (0, 5, 10, and 20wt% in powder) were characterized, the surface morphology and
      composition of the resulting ZZrOE materials were investigated. The ions and
      chemicals released into the cell culture medium from ZOE and ZZrOE (3cm2/mL) were
      measured by inductively coupled plasma atomic emission spectroscopy and gas
      chromatography, respectively. After testing cytotoxicity against hDPSCs using the
      above extracts, the therapeutic effects on lipopolysaccharide-inflamed hDPSCs in
      terms of compromising the upregulation of inflammatory response-related mRNA
      expression were tested using real-time PCR. RESULTS: ZZrOE 20% exhibited
      increased compressive strength (~45%), 3-point flexural strength (~150%) and
      hardness (~75%), as well as a similar setting time (~90%), compared with those of
      ZOE. After the rough surface of ZZrOE was observed, significantly fewer released
      Zn ions and eugenol (~40% of that from ZOE) were detected in ZZrOE 20%. ZZrOE
      showed less cytotoxicity because of the lower amount of Zn ions released from ZOE
      while showing sustained inhibition of inflammatory marker (e.g., interleukin
      1beta, 6 and 8) mRNA levels. SIGNIFICANCE: The improved mechanical properties and
      cytocompatibility, as well as the sustained therapeutic effects on inflamed
      hDPSCs, were investigated in ZZrOE compared with those of ZOE. Therefore, ZZrOE
      has the potential to be used as an alternative to ZOE as a dental restorative
      material.

PMID- 29037478
TI  - Five Hundred Seventy-Six Cases of Video-Assisted Thoracic Surgery Using Local
      Anesthesia and Sedation: Lessons Learned.
AB  - BACKGROUND: General anesthesia and endotracheal intubation are a luxury rather
      than a necessity for many video-assisted thoracic surgery (VATS) operations.
      Twenty-three years ago, I began using local anesthesia and sedation for pleural
      disease and subsequently, for pericardial and lung disease. STUDY DESIGN: The
      records of all patients undergoing VATS using local anesthesia and sedation at
      hospitals of the Geisinger Health System (Danville and Wilkes-Barre, PA), from
      June 1, 2002 to June 30, 2011, and the Lifebridge Health System (Baltimore, MD)
      from July 1, 2011 to March 1, 2017, were retrospectively reviewed. There was 1
      unsuccessful attempt at this technique, and it was eligible for inclusion. No
      patient was excluded based on age, BMI, or comorbidities. No patient had
      endotracheal intubation, laryngeal mask airway, or epidural or nerve block
      analgesia; all patients breathed spontaneously. RESULTS: Five hundred twenty-nine
      patients ranging in age from 21 to 104 years (mean 67 years) underwent 576
      procedures: pleural biopsy-drainage with or without talc (n = 368); drainage of
      empyema (n = 112); lung biopsy (n = 56); evacuation of chronic hemothorax (n =
      23); pericardial window (n = 10); treatment of chylothorax (n = 2); lung abscess
      draining (n = 2); treatment of pneumothorax (n = 2); and mediastinal mass biopsy
      (n = 1). No patient required intubation or conversion to thoracotomy. There were
      12 complications (2%). There were no deaths due to operation. CONCLUSIONS: Video
      assisted thoracic surgery using local anesthesia and sedation is safe and
      effective for many indications. A review of the lessons learned caring for 529
      patients will allow any thoracic surgeon and any anesthesiologist to practice
      this technique.

PMID- 29037477
TI  - Mutational analysis of foot and mouth disease virus nonstructural polyprotein 3AB
      coding region to design a negative marker virus.
AB  - Inactivated purified whole virus vaccines are used for control of foot and mouth
      disease (FMD). ELISAs detecting antibodies to the nonstructural proteins (NSP), a
      marker of infection, are primarily used to differentiate FMD virus (FMDV)
      infected from vaccinated animals (DIVA). However, such DIVA assays have a
      limitation to their specificity since residual NSPs present in the relatively
      impure vaccines are suspected to induce an NSP-antibody response in the
      repeatedly vaccinated animals. Epitope-deleted negative marker vaccine strategy
      seems to have an advantage over the conventional vaccines in identifying the
      infected animals with accuracy. NSP 3AB contains an abundance of immunodominant B
      cell epitopes of diagnostic importance. This study addresses the feasibility of
      producing 3AB-truncated FMDV mutant as a potential negative marker vaccine
      candidate. An infectious cDNA clone of FMDV serotype Asia 1 strain was used to
      engineer an array of deletion mutations in the established antigenic domain of
      3AB. The maximum length of deletion tolerated by the virus was found to be
      restricted to amino acid residues 87-144 in the C-terminal half of 3A protein
      along with deletion of the first two copies of 3B peptide. The 3AB-truncated
      marker virus (Asia 1 IND 491/1997Delta3A87-1443B1,2+FLAG) demonstrated
      infectivity titres comparable to that of the parental virus in BHK-21 (log10 7.42
      TCID50/ml) and LFBK-alphaVbeta6 (log10 8.30 TCID50/ml) cell monolayer culture.
      The protein fragment corresponding to the viable deletion in the 3AB region was
      expressed in a prokaryotic system to standardize a companion assay (3A87-1533B1,2
      I-ELISA) for the negative marker virus which showed reasonably high diagnostic
      sensitivity (96.9%) and specificity (100% for naive and 97.1% for uninfected
      vaccinated samples). The marker virus and its companion ELISA designed in this
      study provide a basis to devise a marker vaccine strategy for FMD control.

PMID- 29037479
TI  - Circulating miRNAs in nontumoral liver diseases.
AB  - In recent years, there has been increasing interest in finding new biomarkers for
      diagnosis and prognostication of liver diseases. MicroRNAs (miRNAs) are small
      noncoding RNA molecules involved in the regulation of gene expression and have
      been studied in relation to several conditions, including liver disease. Mature
      miRNAs can reach the bloodstream by passive release or by incorporation into
      lipoprotein complexes or microvesicles, and have stable and reproducible
      concentrations among individuals. In this review, we summarize studies involving
      circulating miRNAs sourced from the serum or plasma of patients with nontumoral
      liver diseases in attempt to bring insights in the use of miRNAs as biomarkers
      for diagnosis, as well as for prognosis of such diseases. In addition, we present
      pre-analytical aspects involving miRNA analysis and strategies for normalization
      of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) data
      related to the studies evaluated.

PMID- 29037480
TI  - Linking energy sensing to suppression of JAK-STAT signalling: A potential route
      for repurposing AMPK activators?
AB  - Exaggerated Janus kinase-signal transducer and activator of transcription (JAK
      STAT) signalling is key to the pathogenesis of pro-inflammatory disorders, such
      as rheumatoid arthritis and cardiovascular diseases. Mutational activation of
      JAKs is also responsible for several haematological malignancies, including
      myeloproliferative neoplasms and acute lymphoblastic leukaemia. Accumulating
      evidence links adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK),
      an energy sensor and regulator of organismal and cellular metabolism, with the
      suppression of immune and inflammatory processes. Recent studies have shown that
      activation of AMPK can limit JAK-STAT-dependent signalling pathways via several
      mechanisms. These novel findings support AMPK activation as a strategy for
      management of an array of disorders characterised by hyper-activation of the JAK
      STAT pathway. This review discusses the pivotal role of JAK-STAT signalling in a
      range of disorders and how both established clinically used and novel AMPK
      activators might be used to treat these conditions.

PMID- 29037481
TI  - Surgical outcomes among elderly women with endometrial cancer treated by
      laparoscopic hysterectomy: a NRG/Gynecologic Oncology Group study.
AB  - OBJECTIVE: Tolerance of and complications caused by minimally invasive
      hysterectomy and staging in the older endometrial cancer population is largely
      unknown despite the fact that this is the most rapidly growing age group in the
      United States. The objective of this retrospective review was to compare
      operative morbidity by age in patients on the Gynecologic Oncology Group
      Laparoscopic Surgery or Standard Surgery in Treating Patients With Endometrial
      Cancer or Cancer of the Uterus (LAP2) trial. STUDY DESIGN: This is a
      retrospective analysis of patients from Gynecologic Oncology Group LAP2, a trial
      that included clinically early-stage uterine cancer patients randomized to
      laparotomy vs laparoscopy for surgical staging. Differences in the rates and
      types of intraoperative and perioperative complications were compared by age.
      Specifically complications between patients <60 vs >=60 years old were compared
      caused by toxicity analysis showing a sharp increase in toxicity starting at age
      60 years in the laparotomy group. RESULTS: LAP2 included 1477 patients >=60 years
      old. As expected, with increasing age there was worsening performance status and
      disease characteristics including higher rates of serous histology, high-stage
      disease, and lymphovascular space invasion. There was no significant difference
      in lymph node dissection rate by age for the entire population or within the
      laparotomy or laparoscopy groups. Toxicity analysis showed a sharp increase in
      toxicity seen in patients >=60 years old in the laparotomy group. Further
      analysis showed that when comparing laparotomy with laparoscopy in patients <60
      years old vs >=60 years old and controlling for race, body mass index, stage,
      grade, and performance status, patients <60 years old undergoing laparotomy had
      more hospital stays >2 days (odds ratio, 17.48; 95% confidence interval, 11.71
      27.00, P < .001) compared with patients <60 years old undergoing laparoscopy.
      However, when comparing laparotomy with laparoscopy in patients >=60 years old,
      in addition to hospital stay >2 days (odds ratio, 12.77; 95% confidence interval,
      8.74-19.32, P < .001), there were higher rates of the following postoperative
      complications: antibiotic administration (odds ratio, 1.63; 95% confidence
      interval, 1.24-2.14, P < .001), ileus (odds ratio, 2.16; 95% confidence interval,
      1.42-3.31, P <0.001), pneumonias (odds ratio, 2.36; 95% confidence interval, 1.01
      5.66, P = .048), deep vein thromboses (odds ratio, 2.87; 95% confidence interval,
      1.08-8.03, P = .035), and arrhythmias (odds ratio, 3.21; 95% confidence interval,
      1.60-6.65, P = .001) in the laparotomy group. CONCLUSION: Laparoscopic staging
      for uterine cancer is associated with decreased morbidity in the immediate
      postoperative period in patients >=60 years old. These results allow for more
      accurate preoperative counseling. A minimally invasive approach to uterine cancer
      staging may decrease morbidity that could affect long-term survival.

PMID- 29037482
TI  - The prediction of fetal death with a simple maternal blood test at 20-24 weeks: a
      role for angiogenic index-1 (PlGF/sVEGFR-1 ratio).
AB  - BACKGROUND: Fetal death is an obstetrical syndrome that annually affects 2.4 to 3
      million pregnancies worldwide, including more than 20,000 in the United States
      each year. Currently, there is no test available to identify patients at risk for
      this pregnancy complication. OBJECTIVE: We sought to determine if maternal plasma
      concentrations of angiogenic and antiangiogenic factors measured at 24-28 weeks
      of gestation can predict subsequent fetal death. STUDY DESIGN: A case-cohort
      study was designed to include 1000 randomly selected subjects and all remaining
      fetal deaths (cases) from a cohort of 4006 women with a singleton pregnancy,
      enrolled at 6-22 weeks of gestation, in a pregnancy biomarker cohort study. The
      placentas of all fetal deaths were histologically examined by pathologists who
      used a standardized protocol and were blinded to patient outcomes. Placental
      growth factor, soluble endoglin, and soluble vascular endothelial growth factor
      receptor-1 concentrations were measured by enzyme-linked immunosorbent assays.
      Quantiles of the analyte concentrations (or concentration ratios) were estimated
      as a function of gestational age among women who delivered a live neonate but did
      not develop preeclampsia or deliver a small-for-gestational-age newborn. A
      positive test was defined as analyte concentrations (or ratios) <2.5th and 10th
      centiles (placental growth factor, placental growth factor/soluble vascular
      endothelial growth factor receptor-1 [angiogenic index-1] and placental growth
      factor/soluble endoglin) or >90th and 97.5th centiles (soluble vascular
      endothelial growth factor receptor-1 and soluble endoglin). Inverse probability
      weighting was used to reflect the parent cohort when estimating the relative
      risk. RESULTS: There were 11 fetal deaths and 829 controls with samples available
      for analysis between 24-28 weeks of gestation. Three fetal deaths occurred <28
      weeks and 8 occurred >=28 weeks of gestation. The rate of placental lesions
      consistent with maternal vascular underperfusion was 33.3% (1/3) among those who
      had a fetal death <28 weeks and 87.5% (7/8) of those who had this complication
      >=28 weeks of gestation. The maternal plasma angiogenic index-1 value was <10th
      centile in 63.6% (7/11) of the fetal death group and in 11.1% (92/829) of the
      controls. The angiogenic index-1 value was <2.5th centile in 54.5% (6/11) of the
      fetal death group and in 3.7% (31/829) of the controls. An angiogenic index-1
      value <2.5th centile had the largest positive likelihood ratio for predicting
      fetal death >24 weeks (14.6; 95% confidence interval, 7.7-27.7) and a relative
      risk of 29.1 (95% confidence interval, 8.8-97.1), followed by soluble endoglin
      >97.5th centile and placental growth factor/soluble endoglin <2.5th, both with a
      positive likelihood ratio of 13.7 (95% confidence interval, 7.3-25.8) and a
      relative risk of 27.4 (95% confidence interval, 8.2-91.2). Among women without a
      fetal death whose plasma angiogenic index-1 concentration ratio was <2.5th
      centile, 61% (19/31) developed preeclampsia or delivered a small-for-gestational
      age neonate; when the 10th centile was used as the cut-off, 37% (34/92) of women
      had these adverse outcomes. CONCLUSION: (1) A maternal plasma angiogenic index-1
      value <2.5th centile (0.126) at 24-28 weeks of gestation carries a 29-fold
      increase in the risk of subsequent fetal death and identifies 55% of subsequent
      fetal deaths with a false-positive rate of 3.5%; and (2) 61% of women who have a
      false-positive test result will subsequently experience adverse pregnancy
      outcomes.

PMID- 29037484
TI  - Australian midwives views and experiences of practice and politics related to
      water immersion for labour and birth: A web based survey.
AB  - BACKGROUND: There is little published research that has examined practitioners'
      views and experiences of pain relieving measures commonly used during labour and
      birth, particularly for non-pharmacological measures such as water immersion.
      Furthermore, there is minimal published research examining the process of policy
      and guideline development, that is, the translation of published research to
      usable practice guidance. AIMS: The aims of phase three of a larger study were to
      explore midwives knowledge, experiences and support for the option of water
      immersion for labour and birth in practice and their involvement, if any, in
      development of policy and guidelines pertaining to the option. METHODS: Phase
      three of a three phased mixed methods study included a web based survey of 234
      Australian midwives who had facilitated and/or been involved in the development
      of policies and/or guidelines relating to the practice of water immersion.
      FINDINGS: Midwives who participated in this study were supportive of both water
      immersion for labour and birth reiterating documented benefits of reduced pain,
      maternal relaxation and a positive birth experience. The most significant
      concerns were maternal collapse, the difficulty of estimating blood loss and
      postpartum haemorrhage whilst barriers included lack of accredited staff, lifting
      equipment and negative attitudes. Midwives indicated that policy/guideline
      documents limited their ability to facilitate water immersion and did not always
      to support women's informed choice. CONCLUSION: Midwives who participated in this
      study supported the practice of water immersion reiterating the benefits
      documented in the literature and minimal risk to the woman and baby. ETHICAL
      CONSIDERATIONS: The Human Research Ethics Committee of the University of South
      Australia approved the research.

PMID- 29037483
TI  - New labor management guidelines and changes in cesarean delivery patterns.
AB  - BACKGROUND: In 2010 the Consortium on Safe Labor published labor curves. It was
      proposed that the rate of cesarean delivery could be lowered by avoiding the
      diagnosis of arrest of dilation before 6 cm. However, there is little information
      on the uptake of the guidelines and on changes in cesarean delivery rates that
      may have occurred. OBJECTIVE: The objective of the study was to test the
      following hypotheses: (1) among patients laboring at term, rates of arrest of
      dilation disorders have decreased, leading to a decrease in the rate of cesarean
      delivery; (2) in the second stage, pushing duration prior to diagnosis of arrest
      of descent has increased, also leading to a reduction in the rate of cesarean
      delivery for this indication. As a secondary aim, we investigated changes in
      maternal and neonatal morbidity. STUDY DESIGN: This was a secondary analysis of a
      prospective cohort study of all patients presenting at >=37 weeks' gestation from
      2010 through 2014 with a nonanomalous vertex singleton and no prior history of
      cesarean delivery. Rates of cesarean delivery, arrest of dilation, and changes in
      rates of maternal and neonatal morbidity were calculated in crude and adjusted
      models. Cervical dilation at diagnosis of the arrest of dilation, time spent at
      the maximal dilation prior to diagnosis of arrest of dilation, and time in the
      second stage prior to the diagnosis of arrest of descent were compared over the
      study period. RESULTS: There were 7845 eligible patients. The cesarean delivery
      rate in 2010 was 15.8% and, in 2014, 17.7% (P trend = .51). In patients
      undergoing cesarean delivery for the arrest of dilation, the median cervical
      dilation at the time of cesarean delivery was at 5.5 cm in 2010 and 6.0 cm in
      2014 (P trend = .94). In these patients, there was an increase in the time spent
      at last dilation: 3.8 hours in 2010 to 5.2 hours in 2014 (P trend = .02). There
      was no change in the frequency of patients diagnosed with the arrest of dilation
      at <6 cm: 51.4% in 2010 and 48.6% in 2014 (P trend = .56). However, in these
      patients, the median time spent at the last cervical dilation was 4.0 hours in
      2010 and 6.7 hours in 2014 (P trend = .046). There were 206 cesarean deliveries
      for the arrest of descent. The median pushing time in these patients increased in
      multiparous patients from 1.1 hours in 2010 to 3.4 hours in 2014 (P trend =
      .009); in nulliparous patients these times were 2.7 hours in 2010 and 3.8 hours
      in 2014 (P trend = .09). There was a significant trend toward increasing adverse
      neonatal and maternal outcomes (P < .001 for each). The adjusted odds ratio for
      adverse maternal outcome for 2014 compared with 2010 was 1.66 (95% confidence
      interval, 1.27-2.17); however, considering only transfusion, hemorrhage, or
      infection, there was no difference (P trend = .96). The adjusted odds ratio of
      adverse neonatal outcome in 2014 compared with 2010 was 1.80 (95% confidence
      interval, 1.36-2.36). CONCLUSION: Despite significant changes in labor management
      that have occurred over the initial years since publication of the new labor
      curves and associated guidelines, the primary cesarean delivery rate was not
      reduced and there has been an increase in maternal and neonatal morbidity in our
      institution. A randomized controlled trial is needed.

PMID- 29037486
TI  - A research method to explore midwives' views of national maternity service
      reforms.
AB  - BACKGROUND: Priorities of the National Maternity Services Plan (NMSP) are a
      significant contrast to current standard hospital maternity service provision.
      This paper demonstrates the applicability of case study methods to explore the
      views of midwives during a period of midwifery reform. AIM: This research aims to
      highlight key findings and insights surrounding recommended changes facing
      midwives that can be shared with education providers to incorporate strategies
      into education programs to ensure contemporary midwifery practice. METHODS:
      Exploratory Case Study methodology was employed using ethical processes and
      designing semi-structured interview questions to explore participants' views.
      Purposive sampling ensured participants were currently practicing midwives in
      order to reflect the perspective and intent of this study. Data were analysed and
      findings presented in categories and subcategories. RESULTS: Case Study
      methodology enables an in-depth understanding of a phenomenon to be explored
      within a natural context. The participants of this study formed a single unit of
      analysis to ensure the research makes a worthwhile contribution to the profession
      of midwifery. CONCLUSION: This paper demonstrates that Case Study methodology is
      a valid research approach to exploring the views of midwives employed in standard
      care settings during a period of national reform. The rigorous processes and
      versatility of Case Study methodology ensured a systematic, critical enquiry was
      undertaken to gain understanding of the views of participants in implementing the
      NMSP. This understanding is reflective of the real life contexts of midwives to
      promote understanding and provide a body of knowledge where there is ambiguity
      and uncertainty.

PMID- 29037485
TI  - A tale of two pregnancies: A Critical Interpretive Synthesis of women's
      perceptions about delayed initiation of antenatal care.
AB  - BACKGROUND: Delayed access to antenatal care in high income countries is
      associated with poor maternal, fetal and neonatal outcomes. The aim was to
      synthesise the diverse body of evidence around women's views of early antenatal
      care and barriers to attendance in such countries. Critical Interpretive
      Synthesis integrates the process of systematic review with the qualitative
      methods of meta-ethnography and grounded theory, with a focus on theory
      generation to inform policy, practice and future research. METHODS: Database
      searches were conducted, supplemented with reference and citation tracking and
      website searching between February 2014 and April 2016. Qualitative data analysis
      methods were used to extract and summarise the key themes from each study. A
      taxonomy of constructs was created, with the synthesis developed to thread these
      together. Fifty-four papers were synthesised, including qualitative,
      quantitative, mixed method and systematic review, published between 1987 and
      2016. FINDINGS: Seventeen constructs around the core concept of 'acceptance of
      personal and public pregnancies' were produced. Acceptance of the 'personal'
      pregnancy considers the contribution of mindset in the recognition and acceptance
      of pregnancy, influenced by knowledge of pregnancy symptoms, pregnancy planning
      and desire. Acceptance of the 'public' pregnancy considers women's assessment of
      the social consequences of pregnancy, and the relevance and priority of antenatal
      care. CONCLUSION: Critical Interpretive Synthesis offers a systematic yet
      creative approach to the synthesis of diverse evidence. The findings offer new
      perspectives on women's perceptions of early pregnancy and attendance for care,
      which may be used to facilitate timely antenatal provision for all pregnant
      women.

PMID- 29037488
TI  - What is the mechanism of prolonged ileus after colectomy for inflammatory bowel
      disease within the ERAS protocol?

PMID- 29037487
TI  - [Chronic chest pain after rib fracture: It can cause a disability?]
AB  - INTRODUCTION: The rib fractures and instability of the chest wall are the main
      lesions of closed chest trauma. These lesions can be a source of chronic, often
      disabling with daily discomfort resulting limitation of some activities. The
      objective of this study was to assess the prevalence of this phenomenon in order
      to improve the quality of early care. METHODOLOGY: Through an observational
      retrospective cohort study on a number of 41 patients supported and monitored for
      traumatic rib fractures at the Military Hospital of Meknes during the period from
      October 2010 to March 2016. RESULTS: The circumstances of the accident were
      dominated by accidents of public roads (86%) and concerned the young adult male.
      Radiographs have enumerated 165 fracture lines with an average of 4 rib fractures
      per patient. These were unilateral fractures in 88% of cases, and concerned the
      means arc in 46% of cases. The rib fracture was undisplaced fracture in 39% of
      patients, whereas in 2 patients, a flail chest was present. Post-traumatic
      hemothorax (63% of cases) were the thoracic lesions most commonly associated with
      rib fractures. The initial management consisted in the use of analgesics
      systemically in all patients. The retrospective evaluation of pain by the verbal
      scale was possible in 30 patients. The persistent pain was noted in 60% of cases.
      This pain was triggered by a simple effort to moderate in 55% of cases, and hard
      effort in 28% of cases. In 17% of patients, even at rest, the pain occurred
      intermittently. The impact in terms of disability was mild to moderate in 28% of
      cases and important in 17%. The neuropathic pain was found in 3 patients.
      Therapeutically, the first and second levels of analgesics were sufficient to
      relieve pain. The neuroleptics were required for 2 patients. CONCLUSION: Our
      study confirms the persistence of chronic painful, sometimes lasting several
      years after the initial chest trauma. This pain is responsible of disability
      triggered most often after exercise.

PMID- 29037490
TI  - Alzheimer's disease pathogenesis: Is there a role for folate?
AB  - Epigenetic modifications, including changes in DNA methylation, have been
      implicated in a wide range of diseases including neurological diseases such as
      Alzheimer's. The role of dietary folate in providing methyl groups required for
      maintenance and modulation of DNA methylation makes it a nutrient of interest in
      Alzheimer's. Late onset Alzheimer's disease is the most common form of dementia
      and at present its aetiology is largely undetermined. From epidemiological
      studies, the interactions between folate, B-vitamins and homocysteine as well as
      the long latency period has led to difficulties in interpretation of the data,
      thus current evidence exploring the role of dietary folate in Alzheimer's is
      contradictory and unresolved. Therefore, examining the effects at a molecular
      level and exploring potential epigenetic mechanisms could increase our
      understanding of the disease and aetiology. The aim of this review is to examine
      the role that folate could play in Alzheimer's disease neuropathology and will
      focus on the effects of folate on DNA methylation which link to disease
      pathology, initiation and progression.

PMID- 29037489
TI  - Latent HIV-1 TAR Regulates 7SK-responsive P-TEFb Target Genes and Targets
      Cellular Immune Responses in the Absence of Tat.
AB  - The transactivating response element (TAR) structure of the nascent HIV-1
      transcript is critically involved in the recruitment of inactive positive
      transcription elongation factor b (P-TEFb) to the promoter proximal paused RNA
      polymerase II. The viral transactivator Tat is responsible for subsequent P-TEFb
      activation in order to start efficient viral transcription elongation. In the
      absence of the viral transactivator of transcription (Tat), e.g., during latency
      or in early stages of HIV transcription, TAR mediates an interaction of P-TEFb
      with its inhibitor hexamethylene bis-acetamide-inducible protein 1 (HEXIM1),
      keeping P-TEFb in its inactive form. In this study, we address the function of
      HIV-1 TAR in the absence of Tat by analyzing consequences of HIV-1 TAR
      overexpression on host cellular gene expression. An RNA chimera consisting of
      Epstein-Barr virus-expressed RNA 2 (EBER2) and HIV-1 TAR was developed to assure
      robust overexpression of TAR in HEK293 cells. The overexpression results in
      differential expression of more than 800 human genes. A significant proportion of
      these genes is involved in the suppression of cellular immune responses,
      including a significant set of 7SK-responsive P-TEFb target genes. Our findings
      identify a novel role for HIV-1 TAR in the absence of Tat, involving the
      interference with host cellular immune responses by targeting 7SK RNA-mediated
      gene expression and P-TEFb inactivation.

PMID- 29037491
TI  - Molecular identification of polymers and anthropogenic particles extracted from
      oceanic water and fish stomach - A Raman micro-spectroscopy study.
AB  - Pacific Ocean trawl samples, stomach contents of laboratory-raised fish as well
      as fish from the subtropical gyres were analyzed by Raman micro-spectroscopy
      (RMS) to identify polymer residues and any detectable persistent organic
      pollutants (POP). The goal was to access specific molecular information at the
      individual particle level in order to identify polymer debris in the natural
      environment. The identification process was aided by a laboratory generated
      automated fluorescence removal algorithm. Pacific Ocean trawl samples of plastic
      debris associated with fish collection sites were analyzed to determine the types
      of polymers commonly present. Subsequently, stomach contents of fish from these
      locations were analyzed for ingested polymer debris. Extraction of polymer debris
      from fish stomach using KOH versus ultrapure water were evaluated to determine
      the optimal method of extraction. Pulsed ultrasonic extraction in ultrapure water
      was determined to be the method of choice for extraction with minimal chemical
      intrusion. The Pacific Ocean trawl samples yielded primarily polyethylene (PE)
      and polypropylene (PP) particles >1 mm, PE being the most prevalent type.
      Additional microplastic residues (1 mm - 10 MUm) extracted by filtration,
      included a polystyrene (PS) particle in addition to PE and PP. Flame retardant,
      deca-BDE was tentatively identified on some of the PP trawl particles. Polymer
      residues were also extracted from the stomachs of Atlantic and Pacific Ocean
      fish. Two types of polymer related debris were identified in the Atlantic Ocean
      fish: (1) polymer fragments and (2) fragments with combined polymer and fatty
      acid signatures. In terms of polymer fragments, only PE and PP were detected in
      the fish stomachs from both locations. A variety of particles were extracted from
      oceanic fish as potential plastic pieces based on optical examination. However,
      subsequent RMS examination identified them as various non-plastic fragments,
      highlighting the importance of chemical analysis in distinguishing between
      polymer and non-polymer residues.

PMID- 29037492
TI  - Modelling daily PM2.5 concentrations at high spatio-temporal resolution across
      Switzerland.
AB  - Spatiotemporal resolved models were developed predicting daily fine particulate
      matter (PM2.5) concentrations across Switzerland from 2003 to 2013. Relatively
      sparse PM2.5 monitoring data was supplemented by imputing PM2.5 concentrations at
      PM10 sites, using PM2.5/PM10 ratios at co-located sites. Daily PM2.5
      concentrations were first estimated at a 1 * 1km resolution across Switzerland,
      using Multiangle Implementation of Atmospheric Correction (MAIAC) spectral
      aerosol optical depth (AOD) data in combination with spatiotemporal predictor
      data in a four stage approach. Mixed effect models (1) were used to predict PM2.5
      in cells with AOD but without PM2.5 measurements (2). A generalized additive
      mixed model with spatial smoothing was applied to generate grid cell predictions
      for those grid cells where AOD was missing (3). Finally, local PM2.5 predictions
      were estimated at each monitoring site by regressing the residuals from the 1 *
      1km estimate against local spatial and temporal variables using machine learning
      techniques (4) and adding them to the stage 3 global estimates. The global (1 km)
      and local (100 m) models explained on average 73% of the total,71% of the spatial
      and 75% of the temporal variation (all cross validated) globally and on average
      89% (total) 95% (spatial) and 88% (temporal) of the variation locally in measured
      PM2.5 concentrations.

PMID- 29037493
TI  - Ambient concentrations and deposition rates of selected reactive nitrogen species
      and their contribution to PM2.5 aerosols at three locations with contrasting land
      use in southwest China.
AB  - The fast economic development of southwest China has resulted in significant
      increases in the concentrations of reactive nitrogen (Nr) in the atmosphere. In
      this study, an urban (Chengdu, CD), suburban (Shifang, SF) and agriculture
      (Yanting, YT) - dominated location in the Sichuan Province, southwest China, were
      selected to investigate the atmospheric composition of Nr, their concentrations
      and deposition rates. We measured Nr concentrations in precipitation (NH4+, NO3-
      and organic N (DON)), the gas phase (NH3 and NO2), and the aerosol particles
      (PM2.5), and calculated their fluxes over a two year period (2014-2016). Total
      annual N deposition rates were 49.2, 44.7 and 19.8 kg N ha-1 yr-1 at CD, SF and
      YT, respectively. Ammonia concentrations were larger at the urban and suburban
      sites than the agricultural site (12.2, 14.9, and 4.9 MUg N m-3 at CD, SF and YT,
      respectively). This is consistent with the multitude of larger sources of NH3,
      including city garbage, livestock and traffic, in the urban and suburban areas.
      Monthly NO2 concentrations were lower in warmer compared to the colder months,
      but seasonal differences were insignificant. Daily PM2.5 concentrations ranged
      from 7.7 to 236.0, 5.0-210.4 and 4.2-128.4 MUg m-3 at CD, SF and YT,
      respectively, and showed significant correlations with fine particulate NH4+ and
      NO3- concentrations. Ratios of reduced to oxidized N were in the range of 1.6
      2.7. This implies that the control of reduced Nr especially in urban environments
      is needed to improve local air quality.

PMID- 29037494
TI  - Insights into the characteristics and sources of primary and secondary organic
      carbon: High time resolution observation in urban Shanghai.
AB  - There is growing evidence suggesting that organic aerosols play an important role
      in the evolution of severe haze episodes. However, long-term investigations of
      the different characteristics of carbonaceous aerosols during haze and non-haze
      days are insufficient. In this work, hourly measurements of organic carbon (OC)
      and elemental carbon (EC) in PM2.5 were conducted in Shanghai, a megacity in
      Eastern China, over the course of a year from July 2013 to June 2014. Both OC and
      EC exhibited a bimodal diel pattern and were highly dependent on the wind speed
      and direction. The concentration-weighted trajectory (CWT) analysis illustrated
      that primary OC (POC) and EC were largely associated with regional and long-range
      transport. Secondary OC (SOC) formation was the strongest during the harvest
      season owing to significant biomass burning emissions from the adjacent Yangtze
      River Delta and farther agricultural regions. Compared to OC (6.7 MUg m-3) and EC
      (2.0 MUg m-3) in the non-haze days, higher levels of both OC (15.6 MUg m-3) and
      EC (7.7 MUg m-3) were observed in the haze days as expected, but with lower OC/EC
      ratios in the haze days (2.4) than in non-haze days (4.6). The proportion of POC
      and EC in PM2.5 remained relatively constant as a function of PM2.5 mass
      loadings, while that of SOC significantly decreased on the highly polluted days.
      It is concluded that the haze pollution in urban Shanghai was influenced more by
      the primary emissions (POC and EC), while the role of SOC in triggering haze was
      limited.

PMID- 29037495
TI  - Residuals of organophosphate esters in foodstuffs and implication for human
      exposure.
AB  - Foodstuffs may be contaminated by organophosphate esters (OPEs) and become an
      important source of human exposure since OPEs are ubiquitous in the environment.
      In the present study, 10 OPEs were analyzed in various food matrices collected
      from a city in Eastern China including chicken, pork, fishes, vegetables, tofu,
      eggs, milk and cereals. The concentrations of Sigma10OPEs ranged from 1.1 to 9.6
      ng g-1 fresh weight (fw) in the foodstuffs. Cereals had the highest residual
      level of total OPEs with a mean value of 5.7 ng g-1 fw. Tris(2-ethylhexyl)
      phosphate was detected in all foodstuff samples and showed the highest median
      residual concentration of 1.3 ng g-1 fw among the OPE analogs. The daily dietary
      intake of OPEs was calculated as 3.6 and 2.4 MUg d-1 for adults and children.
      Cereals were identified as the major contributor to the total OPEs among
      different types of foodstuffs. Preliminary exposure assessment revealed that the
      current non-cancer health risks of OPEs via dietary intake were in the range of
      10-5-10-3, indicating low risk levels. Moreover, the hazard index of OPEs
      indicated that the risk for children (3 * 10-3) was higher than adults (2 * 10
      3).

PMID- 29037496
TI  - Chronic ingestion of polystyrene microparticles in low doses has no effect on
      food consumption and growth to the intertidal amphipod Echinogammarus marinus?
AB  - The ingestion of microplastics (plastic particles <5 mm) has been observed in a
      range of marine organisms, and adverse effects have been reported in several
      species after high concentration exposure. However, the long-term effects of low
      dose ingestion remains unclear. The aim of this study was thus to assess the
      chronic effects of low concentrations of polystyrene microparticles to the
      intertidal amphipod Echinogammarus marinus, using food consumption, growth, and
      moulting as endpoints. Amphipods were fed a gelatinous algal feed spiked with
      microbeads (8 MUm) in concentrations of ~0.9, 9 and 99 microplastics/g for 35
      days. E. marinus was also analysed for retention of microplastics, and egestion
      rate was calculated in a separate high-dose feeding experiment. No significant
      effects were found in the food consumption or growth assays. There was no
      accumulation of microplastics in the gut, with only one microbead recorded
      internally in three (8%) of the exposed amphipods. The low number is likely
      linked to gastrointestinal functions, allowing for easy egestion of indigestible
      items. This assumption was supported by the observation that after high-dose
      exposure, 60% of E. marinus egested all microbeads within 24 h. This study
      suggests that ingesting low concentrations of 8 MUm microplastics do not impair
      the feeding or growth of amphipods along the exposure period. We hope that
      negative results such as these may further assist in assessing the impact posed
      by microplastics to marine organisms.

PMID- 29037497
TI  - Comparative toxicities of silver nitrate, silver nanocolloids, and silver chloro
      complexes to Japanese medaka embryos, and later effects on population growth
      rate.
AB  - Fish embryo toxicology is important because embryos are more susceptible than
      adults to toxicants. In addition, the aquatic toxicity of chemicals depends on
      water quality. We examined the toxicities to medaka embryos of three types of
      silver-AgNO3, silver nanocolloids (SNCs), and silver ions from silver
      nanoparticle plates (SNPPs)-under three pH conditions (4.0, 7.0, and 9.0) in
      embryo-rearing medium (ERM) or ultrapure water. Furthermore, we tested the later
      life-stage effects of SNCs on medaka and their population growth. "Later-life
      stage effects" were defined here as delayed toxic effects that occurred during
      the adult stage of organisms that had been exposed to toxicant during their early
      life stage only. AgNO3, SNCs, and silver ions were less toxic in ERM than in
      ultrapure water. Release of silver ions from the SNPPs was pH dependent: in ERM,
      silver toxicity was decreased owing to the formation of silver chloro-complexes.
      SNC toxicity was higher at pH 4.0 than at 7.0 or 9.0. AgNO3 was more toxic than
      SNCs. To observe later-life effects of SNCs, larvae hatched from embryos exposed
      to 0.01 mg/L SNCs in ultrapure water were incubated to maturity under clean
      conditions. The mature medaka were then allowed to reproduce for 21 days.
      Calculations using survival ratios and reproduction data indicated that the
      intrinsic population growth rate decreased after exposure of embryos to SNC. SNC
      exposure reduced the extinction time as a function of the medaka population
      carrying capacity.

PMID- 29037499
TI  - Neuropsychiatric and cognitive profile of early Richardson's syndrome,
      Progressive Supranuclear Palsy-parkinsonism and Parkinson's disease.
AB  - INTRODUCTION: The two main variants of Progressive Supranuclear Palsy (PSP),
      Richardson's syndrome (PSP-RS) and PSP-parkinsonism (PSP-P), share motor and non
      motor features with Parkinson's disease (PD) particularly in the early stages.
      This makes the precocious diagnosis more challenging. We aimed at defining
      qualitative and quantitative differences of neuropsychiatric and
      neuropsychological profiles between PSP-P, PSP-RS and PD patients recruited
      within 24 months after the onset of symptoms, in order to clarify if the
      identification of peculiar cognitive and psychiatric symptoms is of help for
      early PSP diagnosis. METHODS: PD (n = 155), PSP-P (n = 11) and PSP-RS (n = 14)
      patients were identified. All patients were submitted to clinical, neurological,
      neuropsychiatric diagnostic evaluation and to a comprehensive neuropsychiatric
      and neuropsychological battery. Predictors of PSP-P and PSP-RS diagnosis were
      identified by multivariate logistic regressions including neuropsychiatric and
      neuropsychological features that differed significantly among groups. RESULTS:
      The three groups differed significantly at the Apathy Rating Scale score and at
      several neuropsychological domains. The multivariate logistic regressions
      indicated that the diagnosis of PSP-RS was predicted by phonological verbal
      fluency deficit whereas the presence of apathy significantly predicted the PSP-P
      diagnosis. CONCLUSION: Peculiar neuropsychiatric and neuropsychological symptoms
      are identifiable very precociously in PSP-P, PSP-RS and PD patients. Early
      phonological verbal fluency deficit identifies patients with PSP-RS whereas
      apathy supports the diagnosis of PSP-P.

PMID- 29037500
TI  - Motor, behavioural, and cognitive correlates of fatigue in early, de novo
      Parkinson disease patients.
AB  - INTRODUCTION: Fatigue is one of the most common and disabling non-motor symptoms
      in Parkinson's disease (PD). The objective of this study was to determine
      prevalence and motor, behavioural, and cognitive correlates of distressing
      fatigue in early, de novo PD patients. METHODS: Eighty-one consecutive de novo PD
      patients (64% men; mean age 65.73 +/- 8.26 years) underwent a comprehensive
      examination, including Parkinson's disease Fatigue Scale (PFS), Epworth
      Sleepiness Scale (ESS), Parkinson's Disease Sleep Scale (PDSS), Beck Depression
      Inventory (BDI), Parkinson's Anxiety Scale (PAS), and Apathy Evaluation Scale
      (AES). Moreover, all patients underwent a detailed neuropsychological evaluation
      exploring attention and working memory, executive functions, memory, visuospatial
      abilities and language. Score of patients with or without distressing fatigue
      (defined as a PFS score >= 8) were compared by Student's t-test or Pearson's chi
      square test. Logistic regression analyses were performed to search for motor and
      non-motor features independently associated with presence of distressing fatigue.
      RESULTS: Twelve (15%) patients presented distressing fatigue. Logistic regression
      identified sleepiness (p = 0.04), "episodic anxiety" subscale of PAS (p = 0.005),
      and "cognitive apathy" subscale of AES (p = 0.017) as the main factors associated
      with distressing fatigue. No significant association was found between diagnosis
      of Mild Cognitive Impairment and distressing fatigue (p = 0.745). CONCLUSION: In
      a sample of consecutive de novo PD patients, distressing fatigue is associated
      with episodic anxiety, cognitive apathy and sleepiness, but not with cognitive
      impairment. Our findings suggest possible shared pathogenic mechanisms underlying
      these non-motor symptoms and foster development of early combined therapeutic
      approaches.

PMID- 29037501
TI  - Lifestyles and Health-Related Outcomes of U.S. Hospital Nurses: A Systematic
      Review.
AB  - BACKGROUND: Nurses' modifiable lifestyles have important health-related
      consequences. PURPOSE: To examine the literature on U.S. hospital nurses'
      activity, diet, and health outcomes of cardiovascular disease (CVD) risks and
      health-related quality of life (HRQOL). METHOD: A systematic review using of the
      literature from June 2006 to June 2016 resulted in 13 studies on U.S. hospital
      nurses' diet, physical activity and CVD and HRQOL outcomes. Methodological rigor
      was assessed using Cummings et al., adapted quality rating tool. DISCUSSION:
      Nurses are at risk for poor health outcomes due to inadequate physical activity
      (60%-74%) and eating a poor quality diet (53%-61%). Fewer than 5% of U.S. nurses
      engage in five healthy lifestyle behaviors (diet, activity, no tobacco, alcohol,
      and weight). Adequate physical activity contributes to better HRQOL and a healthy
      diet reduces CVD risks (hypertension, diabetes mellitus, obesity, stroke).
      CONCLUSIONS: Nurses' inactivity and poor diet increases risks for CVD and
      diminished HRQOL.

PMID- 29037498
TI  - Levodopa-carbidopa intestinal gel in advanced Parkinson's: Final results of the
      GLORIA registry.
AB  - INTRODUCTION: This registry evaluated the 24-month safety and efficacy of
      levodopa-carbidopa intestinal gel (LCIG) treatment in advanced Parkinson's
      disease (PD) patients under routine clinical care. METHODS: Motor fluctuations,
      dyskinesia, non-motor symptoms, quality of life, and safety were evaluated.
      Observations were fully prospective for treatment-naive patients (60% of
      patients) and partially retrospective for patients with <=12 months of pre
      treatment with LCIG (40% of patients). Hours of "On" and "Off" time were assessed
      with a modified version of the Unified Parkinson's Disease Rating Scale part IV
      items 32 and 39. RESULTS: Overall, 375 patients were enrolled by 75 movement
      disorder centers in 18 countries and 258 patients completed the registry. At 24
      months LCIG treatment led to significant reductions from baseline in "Off" time
      (hours/day) (mean +/- SD = -4.1 +/- 3.5, P < 0.001), "On" time with dyskinesia
      (hours/day) (-1.1 +/- 4.8, P = 0.006), Non-Motor Symptom Scale total (-16.7 +/-
      43.2, P < 0.001) and individual domains scores, and Parkinson's Disease
      Questionnaire-8 item total score (-7.1 +/- 21.0, P < 0.001). Adverse events
      deemed to have a possible/probable causal relationship to treatment drug/device
      were reported in 194 (54%) patients; the most frequently reported were decreased
      weight (6.7%), device related infections (5.9%), device dislocations (4.8%),
      device issues (4.8%), and polyneuropathy (4.5%). CONCLUSIONS: LCIG treatment led
      to sustained improvements in motor fluctuations, non-motor symptoms particularly
      sleep/fatigue, mood/cognition and gastrointestinal domains, as well as quality of
      life in advanced PD patients over 24 months. Safety events were consistent with
      the established safety profile of LCIG.

PMID- 29037502
TI  - Diversity and education of the nursing workforce 2006-2016.
AB  - BACKGROUND: The Institute of Medicine (IOM) report, The Future of Nursing,
      included recommendations to increase nurse diversity, the percent of nurses
      obtaining a bachelor's degree, and inter-professional education. PURPOSE: The
      purpose of this paper is to report the progress toward achievement of these
      recommendations. METHODS: We used a longitudinal, multi-state data from four
      cohorts of nurses newly licensed in 2004 to 2005, 2007 to 2008, 2010 to 2011, and
      2014 to 2015 to examine and compare the trends. FINDING: The percentage of males
      who became licensed increased, from 8.8% in 2004 to 2005 cohort to 13.6% in the
      2014 to 2015 cohort. The percentage of white-non-Hispanic nurses who were
      licensed decreased from 78.9% in 2007 to 2008 to 73.8% in 2014 to 2015. These
      differences primarily reflect an increase in white-Hispanic nurses. More nurses
      are obtaining a bachelor's degree as their first professional degree, from 36.6%
      in 2004 to 2005 cohort to 48.5% in 2014 to 2015 cohort. About 40% of the 2014 to
      2015 cohort reported that they learned to work in inter-professional teams.
      Collegial nurse-physician relations had an upward positive trajectory over time
      increasing almost 7%. DISCUSSION: The diversity and education of new nurses have
      increased, but are short of meeting the IOM recommendations.

PMID- 29037504
TI  - An investigation of virulence factors of Legionella pneumophila environmental
      isolates.
AB  - Nine Legionella pneumophila strains isolated from cooling towers and a standard
      strain (L. pneumophila serogroup 1, ATCC 33152, Philadelphia 1) were analyzed and
      compared in terms of motility, flagella structure, ability to form biofilms,
      enzymatic activities (hemolysin, nucleases, protease, phospholipase A,
      phospholipase C, acid phosphatase, alkaline phosphatase and lipase),
      hemagglutination capabilities, and pathogenicity in various host cells
      (Acanthamoeba castellanii ATCC 30234, mouse peritoneal macrophages and human
      peripheral monocytes). All the isolates of bacteria appeared to be motile and
      polar-flagellated and possessed the type-IV fimbria. Upon the evaluation of
      virulence factors, isolate 4 was found to be the most pathogenic strain, while 6
      out of the 9 isolates (the isolates 1, 2, 3, 4, 5, and 7) were more virulent than
      the ATCC 33152 strain. The different bacterial strains exhibited differences in
      properties such as adhesion, penetration and reproduction in the hosts, and
      preferred host type. To our knowledge, this is the first study to compare the
      virulence of environmental L. pneumophila strains isolated in Turkey, and it
      provides important information relevant for understanding the epidemiology of L.
      pneumophila.

PMID- 29037503
TI  - Growth kinetics of Escherichia coli O157:H7 on the epicarp of fresh vegetables
      and fruits.
AB  - Despite the increasing reports on the incidence of fresh vegetables and fruits as
      a possible vehicle for human pathogens, there is currently limited knowledge on
      the growth potential of Escherichia coli O157:H7 on different plant substrates.
      This study analyzed the selective adhesion and growth of E. coli O157:H7 on chili
      habanero (Capsicum chinense L.), cucumber (Cucumis sativus), radish (Raphanus
      sativus), tomato (Lycopersicon esculentum), beet (Beta vulgaris subsp. vulgaris),
      and onion (Allium cepa L.) under laboratory conditions. The Gompertz parameters
      were used to determine the growth kinetics. Scanning electron microscopy was used
      to visualize the adhesion of E. coli O157:H7 on the epicarp of the samples.
      Predictive models were constructed to compare the growth of E. coli O157:H7 on
      the samples with different intrinsic factors and to demonstrate the low
      selectivity of the pathogen. No significant difference was observed in the lag
      phase duration (LPD), generation time (GT), and exponential growth rate (EGR) of
      the pathogen adhered to the samples. The interaction between the microorganism
      and the substrate was less supportive to the growth of E. coli O157:H7 for onion,
      whereas for tomato and cucumber, the time for the microorganism to attain the
      maximum growth rate (M) was significantly longer than that recorded for other
      samples.

PMID- 29037505
TI  - In vitro antimicrobial and antimycobacterial activity and HPLC-DAD screening of
      phenolics from Chenopodium ambrosioides L.
AB  - The main objective of this study was to demonstrate the antimicrobial potential
      of the crude extract and fractions of Chenopodium ambrosioides L., popularly
      known as Santa-Maria herb, against microorganisms of clinical interest by the
      microdilution technique, and also to show the chromatographic profile of the
      phenolic compounds in the species. The Phytochemical screening revealed the
      presence of cardiotonic, anthraquinone, alkaloids, tannins and flavonoids. The
      analysis by HPLC-DAD revealed the presence of rutin in the crude extract (12.5+/
      0.20mg/g), ethyl acetate (16.5+/-0.37mg/g) and n-butanol (8.85+/-0.11mg/g),
      whereas quercetin and chrysin were quantified in chloroform fraction (1.95+/-0.04
      and 1.04+/-0.01mg/g), respectively. The most promising results were obtained with
      the ethyl acetate fraction, which inhibited a greater number of microorganisms
      and presented the lowest values of MIC against Staphylococcus aureus and
      Enterococcus faecalis (MIC=0.42mg/mL), Pseudomonas aeruginosa (MIC=34.37mg/mL),
      Paenibacillus apiarus (MIC=4.29mg/mL) and Paenibacillus thiaminolyticus
      (MIC=4.29mg/mL). Considering mycobacterial inhibition, the best results were
      obtained by chloroform fraction against M. tuberculosis, M. smegmatis, and M.
      avium (MIC ranging from 156.25 to 625MUg/mL). This study proves, in part, that
      the popular use of C. ambrosioides L. can be an effective and sustainable
      alternative for the prevention and treatment of diseases caused by various
      infectious agents.

PMID- 29037506
TI  - Neural signatures of dynamic emotion constructs in the human brain.
AB  - How is emotion represented in the brain: is it categorical or along dimensions?
      In the present study, we applied multivariate pattern analysis (MVPA) to
      magnetoencephalography (MEG) to study the brain's temporally unfolding
      representations of different emotion constructs. First, participants rated 525
      images on the dimensions of valence and arousal and by intensity of discrete
      emotion categories (happiness, sadness, fear, disgust, and sadness). Thirteen new
      participants then viewed subsets of these images within an MEG scanner. We used
      Representational Similarity Analysis (RSA) to compare behavioral ratings to the
      unfolding neural representation of the stimuli in the brain. Ratings of valence
      and arousal explained significant proportions of the MEG data, even after
      corrections for low-level image properties. Additionally, behavioral ratings of
      the discrete emotions fear, disgust, and happiness significantly predicted early
      neural representations, whereas rating models of anger and sadness did not.
      Different emotion constructs also showed unique temporal signatures. Fear and
      disgust - both highly arousing and negative - were rapidly discriminated by the
      brain, but disgust was represented for an extended period of time relative to
      fear. Overall, our findings suggest that 1) dimensions of valence and arousal are
      quickly represented by the brain, as are some discrete emotions, and 2) different
      emotion constructs exhibit unique temporal dynamics. We discuss implications of
      these findings for theoretical understanding of emotion and for the interplay of
      discrete and dimensional aspects of emotional experience.

PMID- 29037507
TI  - Gamma oscillations in the superior colliculus and pulvinar in response to faces
      support discrimination performance in monkeys.
AB  - The subcortical visual pathway including the superior colliculus (SC), pulvinar,
      and amygdala has been implicated in unconscious visual processing of faces, eyes,
      and gaze direction in blindsight. Our previous studies reported that monkey SC
      and pulvinar neurons responded preferentially to images of faces while performing
      a delayed non-matching to sample (DNMS) task to discriminate different visual
      stimuli (Nguyen et al., 2013, 2014). However, the contribution of SC and pulvinar
      neurons to the discrimination of the facial images and subsequent behavioral
      performance remains unknown. Since gamma oscillations have been implicated in
      sensory and cognitive processes as well as behavioral execution, we hypothesized
      that gamma oscillations during neuronal responses might contribute to achieving
      the appropriate behavioral performance (i.e., a correct response). In the present
      study, we re-analyzed those neuronal responses in the monkey SC and pulvinar to
      investigate possible relationships between gamma oscillations in these neurons
      and behavioral performance (correct response ratios) during the DNMS task. Gamma
      oscillations of SC and pulvinar neuronal activity were analyzed in three phases
      around the stimulus onset [inter-trial interval (ITI): 1000ms before trial onset;
      Early: 0-200ms after stimulus onset; and Late: 300-500ms after stimulus onset].
      We found that human facial images elicited stronger gamma oscillations in the
      early phase than the ITI and late phase in both the SC and pulvinar neurons.
      Furthermore, there was a significant correlation between strengths of gamma
      oscillations in the early phase and behavioral performance in both the SC and
      pulvinar. The results suggest that gamma oscillatory activity in the SC and
      pulvinar contributes to successful behavioral performance during unconscious
      perceptual and behavioral processes.

PMID- 29037508
TI  - Leveraging Chemotype-Specific Resistance for Drug Target Identification and
      Chemical Biology.
AB  - Identifying the direct physiological targets of drugs and chemical probes remains
      challenging. Here we describe how resistance can be used to achieve 'gold
      standard' validation of a chemical inhibitor's direct target in human cells. This
      involves demonstrating that a silent mutation in the target that suppresses
      inhibitor activity in cell-based assays can also reduce inhibitor potency in
      biochemical assays. Further, phenotypes due to target inhibition can be
      identified as those observed in the inhibitor-sensitive cells, across a range of
      inhibitor concentrations, but not in genetically matched cells with a silent
      resistance-conferring mutation in the target. We propose that chemotype-specific
      resistance, which is generally considered to be a limitation of molecularly
      targeted agents, can be leveraged to deconvolve the mechanism of action of drugs
      and to properly use chemical probes.

PMID- 29037509
TI  - Structure determination of disease associated peak AAA from l-Tryptophan
      implicated in the eosinophilia-myalgia syndrome.
AB  - The eosinophilia-myalgia syndrome (EMS) outbreak of 1989 that occurred in the USA
      and elsewhere was caused by the ingestion of l-Tryptophan (L-Trp) solely
      manufactured by the Japanese company Showa Denko K.K. (SD). Six compounds present
      in the SD L-Trp were reported to be case-associated contaminants. However, "one"
      of these compounds, Peak AAA has remained structurally uncharacterized, despite
      the fact that it was described as "the only statistically significant (p=0.0014)
      contaminant". Here, we employ on-line microcapillary-high performance liquid
      chromatography-electrospray ionization mass spectrometry (LC-MS), and tandem mass
      spectrometry (MS/MS) to determine that Peak AAA is in fact two structurally
      related isomers. Peak AAA1 and Peak AAA2 differed in LC retention times, and were
      determined by accurate mass-LC-MS to both have a protonated molecular ion (MH+)
      of mass 343.239Da (Da), corresponding to a molecular formula of C21H30N2O2, and
      possessing eight degrees of unsaturation (DoU) for the non-protonated molecule.
      By comparing the LC-MS and LC-MS-MS retention times and spectra with authentic
      synthetic standards, Peak AAA1 was identified as the intermolecular condensation
      product of L-Trp with anteiso 7-methylnonanoic acid, to afford (S)-2-amino-3-(2
      ((S,E)-7-methylnon-1-en-1-yl)-1H-indol-3-yl)propanoic acid. Peak AAA2 was
      determined to be a condensation product of L-Trp with decanoic acid, which
      produced (S)-2-amino-3-(2-((E)-dec-1-en-1-yl)-1H-indol-3-yl)propanoic acid.

PMID- 29037510
TI  - From swarm models to behavioural economical systems: Comment on "Modeling human
      behavior in economics and social science" by Marina Dolfin, Leone Leonida and
      Nisrine Outada.

PMID- 29037511
TI  - Comment on "Mistakes and inconsistencies regarding adsorption of contaminants
      from aqueous solution: A critical review, published by Tran et al. [Water
      Research 120, 2017, 88-116]".
AB  - Correct treatment of adsorption thermodynamics requires consistent handling of
      adsorption isotherms and the corresponding sorption coefficients. The present
      comment points to some inconsistencies and misunderstandings in a recent review
      article.

PMID- 29037512
TI  - Treatment outcomes and associated factors among extremely preterm infants in a
      major children hospital in Guangxi, China.
AB  - BACKGROUND: In developing countries, infant survival rate and long-term outcomes
      of extremely preterm infants(EPIs) have significantly improved due to advances in
      perinatal care. The striking gap in the treatment outcome of EPIs between China
      and the other developed countries was a major concern. To assess treatment
      outcomes and associated factors among EPIs in Nanning, China. METHODS: This was a
      perspective study consisting of eligible cases with gestational age between 22
      and 28 weeks and infants were followed to 18-24 months of age. Data including
      clinical characteristics, perinatal factors and after-birth conditions were
      collected from the neonatal intensive care unit (NICU) in a major women's and
      children's health hospital in Guangxi Province from January 1st 2010 to February
      1st 2015. RESULTS: During that period 79 EPIs were born in the hospital. Twenty
      eight infants died in hospital after their parents decided to withdraw clinical
      treatment. Of the 51 surviving infants, 5 infants were lost to follow-up. Eleven
      of the 46 infants were evaluated at 18-24 months of age and were diagnosed with
      neurodevelopmental disability and 35 infants showed normal motor language
      development. The incidence of intrauterine infection and intraventricular
      hemorrhage (IVH) grade III were both higher in the group of infants who were
      diagnosed neurodevelopmental disability than in the group of infants with normal
      motor language development (p < 0.05). Logistic regression analysis showed that
      intrauterine infection (OR = 33.290, 95%CI = 2.180-508.351) and IVH grade III (OR
      = 26.814, 95%CI = 3.631-197.989) were the major risk factors for
      neurodevelopmental disability in EPIs. CONCLUSIONS: Intrauterine infection and
      IVH grade III were associated with the neurodevelopmental disability in EPIs.

PMID- 29037513
TI  - Comparison of Abiraterone Acetate and Docetaxel with Androgen Deprivation Therapy
      in High-risk and Metastatic Hormone-naive Prostate Cancer: A Systematic Review
      and Network Meta-analysis.
AB  - CONTEXT: Randomized clinical trials have recently examined the benefit of adding
      docetaxel or abiraterone to androgen deprivation therapy (ADT) in hormone-naive
      advanced prostate cancer (PCa). OBJECTIVE: To perform a systematic review and
      network meta-analysis of randomized clinical trials, indirectly evaluating
      overall survival (OS) for men treated with abiraterone acetate plus
      prednisone/prednisolone with ADT (Abi-ADT) versus docetaxel with ADT (Doce-ADT)
      in hormone-naive high-risk and metastatic PCa. EVIDENCE ACQUISITION: Medline,
      Embase, Web of Science, Scopus, and Clinicaltrials.gov databases were searched in
      August 2017. We pooled results using the inverse variance technique and random
      effects models. The Bucher technique for indirect treatment comparison was used
      to compare Abi-ADT with Doce-ADT. A priori subgroup and sensitivity analyses were
      performed. EVIDENCE SYNTHESIS: Overall, 6067 patients from five trials were
      included: 1181 (19.5%) patients who received Doce-ADT, 1557 (25.7%) patients who
      received Abi-ADT, and 3329 (54.9%) patients who received ADT-alone. There was a
      total of 1921 deaths: 391 in the Doce-ADT group, 353 in the Abi-ADT group, and
      1177 in the ADT-only group. The pooled hazard ratio (HR) for OS was 0.75 (95%
      confidence interval [CI]: 0.63-0.91, I2=51%, 3 trials, 2951 patients) for Doce
      ADT versus ADT-alone and 0.63 (95% CI: 0.55-0.72, I2=0%, 2 trials, 3116 patients)
      for Abi-ADT versus ADT-alone. The indirect comparison of Abi-ADT to Doce-ADT
      demonstrated no statistically significant difference in OS between these
      approaches (HR: 0.84, 95% CI: 0.67-1.06). Findings were similar in various a
      priori subset analyses, including patients with metastatic disease. Bayesian
      analyses demonstrated comparable results (HR: 0.83, 95% CI: 0.63-1.16). Despite
      the lack of statistical significance, Surface Under the Cumulative Ranking
      Analysis demonstrated an 89% probability that Abi-ADT was preferred. CONCLUSIONS:
      We did not identify a significant difference in OS between Abi-ADT and Doce-ADT
      for men with hormone-naive high-risk or metastatic PCa, although Bayesian
      analysis demonstrates a high likelihood that Abi-ADT was preferred. PATIENT
      SUMMARY: We synthesized the evidence available from studies examining the
      administration of docetaxel or abiraterone in combination with hormonal therapy
      for patients with newly diagnosed, advanced prostate cancer. While these studies
      did not directly compare these agents, we used methodological techniques to
      indirectly compare them and found no significant difference in overall survival.

PMID- 29037514
TI  - Re: Association Between Combined TMPRSS2:ERG and PCA3 RNA Urinary Testing and
      Detection of Aggressive Prostate Cancer.

PMID- 29037515
TI  - Re: Vasileios I. Sakalis, Markos Karavitakis, Dina Bedretdinova, et al. Medical
      Treatment of Nocturia in Men with Lower Urinary Tract Symptoms: Systematic Review
      by the European Association of Urology Guidelines Panel for Male Lower Urinary
      Tract Symptoms. Eur Urol 2017;72:757-69.

PMID- 29037517
TI  - Comparative studies of different types of osteosynthesis on the human corpse
      preparation in bilateral antero-lateral flail chest.
AB  - INTRODUCTION: Bilateral flail chest injuries are challenging in treatment and
      comparatively often require an operative stabilization of the anterior chest wall
      to re-establish normal physiological conditions of the chest wall in shape and
      statics. Various procedures have been described which are technically
      sophisticated for the surgeon. Consequently there is an increasing interest in
      potentials of operative care and their effectiveness on the anterolateral chest
      wall. MATERIALS AND METHODS: 12 Human cadavers were prepared and the natural
      Sternum Position (NP) was marked. A digital probe was fixed to the sternum at the
      height of the 4th intercostal space in order to measure and compare the stability
      of the thorax. Readings were taken of the sternal displacement at 1-5cm sagittal
      distance from NP in starting conditions and from every combination of materials.
      Serial osteotomies were performed on 2 locations on ribs 2-8 to induce bilateral
      flail chest. Afterwards the stabilization was achieved with different implants:
      RESULTS: The osteotomies lead to a subsidence of the sternum occurred to almost
      75 mm from NP which corresponds to a maximal unstable situation. The unstable
      chest wall showed substantially more stabilization through the use of locking
      plates. Our materialcombinations showed a stability of up to 60% of normal. The
      more ribs were treated osteosynthetically, the higher the stability of the chest
      wall. DISCUSSION AND CONCLUSIONS: Locking plate fixation offers anatomically
      realignment of the ribs whereas metal strut support only lifts up the chest wall,
      but could not provide realignment of the dislocated ribs.

PMID- 29037516
TI  - Statin use and knee osteoarthritis progression: Results from a post-hoc analysis
      of the SEKOIA trial.
AB  - OBJECTIVE: Epidemiological and experimental studies have suggested that lipid
      disorders might be involved in the pathophysiology of knee osteoarthritis (OA).
      Studies assessing the effect of statins on knee OA progression have shown
      conflicting results. We investigated the impact of statin use on radiological
      progression in patients with radiological and symptomatic knee OA. METHODS: In
      total, 336 patients from the placebo arm of SEKOIA trial completed the 3-year
      follow-up and were included in this post-hoc analysis. Statin use was recorded at
      baseline interview. Minimal medial tibiofemoral joint space was measured on plain
      radiographs by an automated method at baseline and then annually. Radiologic
      progression was defined as joint space narrowing>=0.5mm over 3 years. RESULTS:
      Overall, 71 patients were statin users (21.1%). They had a higher BMI (31.1+/-5.3
      vs. 29.3+/-5.2kg/m2, P=0.008), a higher sum of metabolic factors (>=3 factors:
      43.7% vs 7.2%; P for trend<0.001) and a higher rate of radiological progression
      (49.3% vs. 32.1%, P=0.007) as compared to statin non-users. The significant
      association between radiological progression and statin use was independent of
      age, gender, WOMAC global score, disease duration, baseline joint space width,
      hypertension, type 2 diabetes, obesity (BMI>30kg/m2) and cardiovascular diseases
      [relative risk 1.49 (95% CI: 1.10-2.02), P=0.010]. CONCLUSION: Among patients
      with knee OA, statin use was associated with radiological worsening over 3 years,
      regardless of other potential confounding factors (obesity, type 2 diabetes,
      hypertension, disease duration, symptom intensity and radiological severity).

PMID- 29037518
TI  - Factors affecting the outcomes of modified tension band wiring techniques in
      transverse patellar fractures.
AB  - INTRODUCTION: Modified tension band wiring has been widely used to treat
      transverse patellar fractures. However, few studies have evaluated the clinical
      outcomes using different methods of Kirschner wire bending, location of the
      tension band, and depths of Kirschner wires. Thus, we tried to clarify these
      factors according to our clinical outcomes. PATIENTS AND METHODS: This
      retrospective cohort study recruited consecutive patients underwent surgical
      fixation for patellar fractures using modified tension band technique between
      January 2010 and December 2015. Different factors in this procedure, including
      the bending manner of the Kirschner wires, their depth, and location of the
      tension band with respect to the superior and inferior border of the patella were
      recorded and analysed. The primary outcome was early loss of fixation. The
      secondary outcomes were minor loss of reduction, implant breakage, deep
      infection, and the need for implant removal. RESULTS: This study included 170
      patients with patellar fractures. Regarding the bending method, similar results
      were obtained with bilaterally or proximally bent Kirschner wires. Regarding
      length, the tension band was placed closely (within 25% of the patella length) in
      124 patients and distantly in 46 patients. The rates of loss of reduction and
      implant breakage were significantly higher in the distantly placed tension bands.
      Regarding depth, 37 patellar fractures were fixed with the Kirschner wires at the
      superficial one third of the patellae while the K- wires at the middle layer of
      patella were used in the remaining 133 patellar fractures. A significantly higher
      rate of minor loss of reduction was obtained using the superficial Kirschner
      wires. CONCLUSION: The modified tension band technique for transverse patella
      fractures provides favourable clinical outcomes, with low failure (5%) and
      infection (2%) rates. Implant irritation is the major complication, and almost
      half of cases require implant removal. The location of the tension band with
      respect to the superior and inferior border of the patella plays an important
      role in clinical outcomes. Placing the wire close to the patella may prevent
      major loss of reduction and implant breakage. Superficially placed Kirschner
      wires also affect clinical outcomes by increasing the rate of minor loss of
      reduction.

PMID- 29037519
TI  - The Akt-like kinase of Leishmania panamensis: As a new molecular target for drug
      discovery.
AB  - The Akt-like kinase of Leishmania spp. is a cytoplasmic orthologous protein of
      the serine/threonine kinase B-PKB/human-Akt group, which is involved in the
      cellular survival of these parasites. By the application of a computational
      strategy we obtained two specific inhibitors of the Akt-like protein of L.
      panamensis (UBMC1 and UBMC4), which are predicted to bind specifically to the
      pleckstrin domain (PH) of the enzyme. We show that the Akt-like of Leishmania
      panamensis is phospho-activated in parasites under nutritional and thermic
      stress, this phosphorylation is blocked by the UBMC1 and UMBC2 and such
      inhibition leads to cell death. Amongst the effects caused by the inhibitors on
      the parasites we found high percentage of hypodiploidy and loss of mitochondrial
      membrane potential. Ultrastructural studies showed highly vacuolated cytoplasm,
      as well as shortening of the flagellum, loss of nuclear membrane integrity and
      DNA fragmentation. Altogether the presented results suggest that the cell death
      caused by UMBC1 and UMBC4 may be associated to an apoptosis-like process. The
      compounds present an inhibitory concentration (IC50) over intracellular
      amastigotes of L. panamensis of 9.2+/-0.8MUM for UBMC1 and 4.6+/-1.9MUM for
      UBMC4. The cytotoxic activity for UBMC1 and UBMC4 in human macrophages derived
      from monocytes (huMDM) was 29+/-1.2MUM and >40MUM respectively. Our findings
      strongly support that the presented compounds can be plausible candidates as a
      new therapeutic alternative for the inhibition of specific kinases of the
      parasite.

PMID- 29037520
TI  - Immunization with LJM11 salivary protein protects against infection with
      Leishmania braziliensis in the presence of Lutzomyia longipalpis saliva.
AB  - Leishmania is transmitted in the presence of sand fly saliva. Protective immunity
      generated by saliva has encouraged identification of a vector salivary-based
      vaccine. Previous studies have shown that immunization with LJM11, a salivary
      protein from Lutzomyia longipalpis, is able to induce a Th1 immune response and
      protect mice against bites of Leishmania major-infected Lutzomyia longipalpis.
      Here, we further investigate if immunization with LJM11 recombinant protein is
      able to confer cross-protection against infection with Leishmania braziliensis
      associated with salivary gland sonicate (SGS) from Lutzomyia intermedia or Lu.
      longipalpis. Mice immunized with LJM11 protein exhibited an increased production
      of anti-LJM11 IgG, IgG1 and IgG2a and a DTH response characterized by an
      inflammatory infiltrate with the presence of CD4+ IFN-gamma+ T cells. LJM11
      immunized mice were intradermally infected in the ear with L. braziliensis in the
      presence of Lu. longipalpis or Lu. intermedia SGS. A significant reduction of
      parasite numbers in the ear and lymph node in the group challenged with L.
      braziliensis plus Lu. longipalpis SGS was observed, but not when the challenge
      was performed with L. braziliensis plus Lu. intermedia SGS. A higher specific
      production of IFN-gamma and absence of IL-10 by lymph node cells were only
      observed in LJM11 immunized mice after infection. After two weeks, a similar
      frequency of CD4+ IFN-gamma+ T cells was detected in LJM11 and BSA groups
      challenged with L. braziliensis plus Lu. longipalpis SGS, suggesting that early
      events possibly triggered by immunization are essential for protection against
      Leishmania infection. Our findings support the specificity of saliva-mediated
      immune responses and reinforce the importance of identifying cross-protective
      salivary antigens.

PMID- 29037521
TI  - [Intracardiac tumor causing recurrent central retinal artery occlusions].

PMID- 29037524
TI  - T-regulatory cells-Triumph of perseverance: The Crafoord Prize for Polyarthritis
      in 2017.
AB  - The Crafoord Prize in Polyarthritis ranks as one of the most prestigious prizes
      and can be awarded only if the Royal Swedish Academy of Sciences decides the
      likelihood of prize worthy progress in the field, and at most every 4th year.
      This has happened only four times since 1982. This year the 5th Laureates were
      Shimon Sakaguchi, Fred Ramsdell, and Alexander Rudensky with the motivation "for
      their discoveries relating to regulatory T cells, which counteract harmful immune
      reactions in arthritis and other autoimmune diseases". Here I review the history
      of their contributions and its impact in rheumatology.

PMID- 29037523
TI  - A systematic review of measurement properties of patient reported outcome
      measures in psoriatic arthritis: A GRAPPA-OMERACT initiative.
AB  - BACKGROUND: An updated psoriatic arthritis (PsA) core outcome set (COS) for
      randomized controlled trials (RCTs) was endorsed at the Outcome Measures in
      Rheumatology (OMERACT) meeting in 2016. OBJECTIVES: To synthesize the evidence on
      measurement properties of patient reported outcome measures (PROMs) for PsA and
      thereby contribute to development of a PsA core outcome measurement set (COMS) as
      described by the OMERACT Filter 2.0. METHODS: A systematic literature search was
      performed in EMBASE, MEDLINE and PsycINFO on Jan 1, 2017 to identify full-text
      articles with an aim of assessing the measurement properties of PROMs in PsA. Two
      independent reviewers rated the quality of studies using the COnsensus based
      standards for the Selection of health Measurement INstruments (COSMIN) checklist,
      and performed a qualitative evidence synthesis. RESULTS: Fifty-five studies were
      included in the systematic review. Forty-four instruments and a total of 89
      scales were analyzed. PROMs measuring COS domains with at least fair quality
      evidence for good validity and reliability (and no evidence for poor properties)
      included the Stockerau Activity Score for PsA (German), Psoriasis Symptom
      Inventory, visual analogue scale for Patient Global, 36 Item Short Form Health
      Survey Physical Function subscale, Health Assessment Questionnaire Disability
      Index, Bath Ankylosing Spondylitis Functional Index, PsA Impact of Disease
      questionnaire, PsA Quality of Life questionnaire, VITACORA-19, Functional
      Assessment of Chronic Illness Therapy Fatigue scale and Social Role Participation
      Questionnaire. CONCLUSIONS: At least one PROM with some evidence for aspects of
      validity and reliability was available for six of the eight mandatory domains of
      the PsA COS.

PMID- 29037522
TI  - Rheumatoid arthritis and risk of chronic obstructive pulmonary disease or asthma
      among women: A marginal structural model analysis in the Nurses' Health Study.
AB  - OBJECTIVE: We investigated whether RA increases risk for chronic obstructive
      pulmonary disease (COPD) or asthma independent of factors occurring before RA
      onset or mediating these respiratory morbidities after diagnosis, such as
      cigarette smoking. METHODS: Within the prospective Nurses' Health Study (n =
      121,701 women; 1976-2014), we identified an incident RA cohort and matched each
      woman with RA to 10 comparators without RA by age and year at index date of RA
      diagnosis, excluding women with COPD or asthma at baseline. Data were obtained
      through biennial questionnaires and medical records. We used marginal structural
      models to determine the independent effect of RA on incident COPD or asthma
      adjusting for confounders and time-varying mediators through inverse probability
      weighting. RESULTS: We identified 843 women with RA, matched to 8,399 comparators
      without RA. Mean age was 59.8 years and mean follow-up after index date was 18.6
      years (SD = 9.0) for women with RA, and 18.8 years (SD = 9.5) for comparators. We
      identified 68 (8.1%) incident COPD and 40 (4.7%) asthma cases among women with
      RA, and 459 (5.5%) COPD and 268 (3.2%) asthma cases among comparators. RA was
      associated with increased risk of COPD (HR = 1.52, 95% CI: 1.17-1.97) and asthma
      (HR = 1.55, 95% CI: 1.11-2.16) compared to comparators adjusted for the matching
      factors of age and calendar year at index date. After further adjustment for
      confounders and time-varying mediators occurring after index date, including
      smoking, RA was significantly associated with COPD (HR = 1.68, 95% CI: 1.36
      2.07), but not asthma (HR = 1.11, 95% CI: 0.59-2.09) compared to non-RA
      comparators. Women with seropositive RA (HR = 1.60, 95% CI: 1.17-2.19) and
      seronegative RA (HR = 1.62, 95% CI: 1.09-2.40) had similar increased risk for
      COPD compared to non-RA comparators. CONCLUSION: In this prospective cohort
      study, RA was associated with increased risk for incident COPD, independent of
      lifestyle confounders and mediators after diagnosis, including smoking.

PMID- 29037525
TI  - Can the Antimicrobial Resistance Benchmark blaze a new trail?

PMID- 29037526
TI  - SIRS in the Time of Sepsis-3.
AB  - Severe sepsis is a common, deadly, and diagnostically vexing condition. Recent
      recommendations for diagnosing sepsis, referred to as consensus guidelines,
      provide a definition of sepsis and remove the systemic inflammatory response
      syndrome (SIRS) as a component of the diagnostic process. A concise definition of
      sepsis is welcomed. However, the approach to developing these guidelines,
      although thorough, had weaknesses. Emphasis is placed on mortality prediction
      rather than on early diagnosis. Diagnostic criteria are recommended to replace
      current criteria without evidence of any effect that their use would have on
      mortality. SIRS is a prevalent feature of patients with sepsis, should remain an
      important component of the diagnostic process, and remains a valuable term for
      discussing patients with life-threatening organ dysfunction caused by infection.

PMID- 29037528
TI  - Driving Pressure and Hospital Mortality in Patients Without ARDS: A Cohort Study.
AB  - BACKGROUND: Driving pressure (DeltaP) is associated with mortality in patients
      with ARDS and with pulmonary complications in patients undergoing general
      anesthesia. Whether DeltaP is associated with outcomes of patients without ARDS
      who undergo ventilation in the ICU is unknown. Our objective was to determine the
      independent association between DeltaP and outcomes in mechanically ventilated
      patients without ARDS on day 1 of mechanical ventilation. METHODS: This was a
      retrospective analysis of a cohort of 622 mechanically ventilated adult patients
      without ARDS on day 1 of mechanical ventilation from five ICUs in a tertiary
      center in the United States. The primary outcome was hospital mortality. The
      presence of ARDS was determined using the minimum daily Pao2 to Fio2 (PF) ratio
      and an automated text search of chest radiography reports. The data set was
      validated by first testing the model in 543 patients with ARDS. RESULTS: In
      patients without ARDS on day 1 of mechanical ventilation, DeltaP was not
      independently associated with hospital mortality (OR, 1.01; 95% CI, 0.97-1.05).
      The results of the primary analysis were confirmed in a series of preplanned
      sensitivity analyses. CONCLUSIONS: In this cohort of patients without ARDS on day
      1 of mechanical ventilation and within the limits of ventilatory settings
      normally used by clinicians, DeltaP was not associated with hospital mortality.
      This study also confirms the association between DeltaP and mortality in patients
      with ARDS not enrolled in a trial and in hypoxemic patients without ARDS.

PMID- 29037527
TI  - CORK Study in Cystic Fibrosis: Sustained Improvements in Ultra-Low-Dose Chest CT
      Scores After CFTR Modulation With Ivacaftor.
AB  - BACKGROUND: Ivacaftor produces significant clinical benefit in patients with
      cystic fibrosis (CF) with the G551D mutation. Prevalence of this mutation at the
      Cork CF Centre is 23%. This study assessed the impact of cystic fibrosis
      transmembrane conductance regulator modulation on multiple modalities of patient
      assessment. METHODS: Thirty-three patients with the G551D mutation were assessed
      at baseline and prospectively every 3 months for 1 year after initiation of
      ivacaftor. Change in ultra-low-dose chest CT scans, blood inflammatory mediators,
      and the sputum microbiome were assessed. RESULTS: Significant improvements in
      FEV1, BMI, and sweat chloride levels were observed post-ivacaftor treatment.
      Improvement in ultra-low-dose CT imaging scores were observed after treatment,
      with significant mean reductions in total Bhalla score (P < .01), peribronchial
      thickening (P = .035), and extent of mucous plugging (P < .001). Reductions in
      circulating inflammatory markers, including interleukin (IL)-1beta, IL-6, and IL
      8 were demonstrated. There was a 30% reduction in the relative abundance of
      Pseudomonas species and an increase in the relative abundance of bacteria
      associated with more stable community structures. Posttreatment community
      richness increased significantly (P = .03). CONCLUSIONS: Early and sustained
      improvements on ultra-low-dose CT scores suggest it may be a useful method of
      evaluating treatment response. It paralleled improvement in symptoms, circulating
      inflammatory markers, and changes in the lung microbiota.

PMID- 29037529
TI  - The Relationship Between Tobacco Smoke Exposure and Airflow Obstruction in US
      Children: Analysis of the National Health and Nutrition Examination Survey (2007
      2012).
AB  - BACKGROUND: It has been difficult to determine the individual impact of prenatal
      and postnatal tobacco smoke exposure (TSE) on childhood lung function, as
      children are often exposed to both. OBJECTIVE: The goal of this study was to
      determine the association between current TSE and airflow obstruction while
      adjusting for self-reported prenatal TSE. METHODS: Children aged 6 to 11 years
      who participated in the National Health and Nutrition Examination Survey (2007
      2012) who had serum cotinine levels measured and spirometry performed were
      included. Logistic regression was used to determine the association between log
      transformed serum cotinine level and airflow obstruction while adjusting for
      confounders; the analysis was then stratified according to asthma status. The
      final model included both log-transformed serum cotinine level and prenatal
      exposure as covariates. RESULTS: The sample consisted of 2,070 children; 9.6% had
      airflow obstruction. The association between cotinine levels and airflow
      obstruction was significant in an unadjusted analysis (OR, 1.12 [95% CI, 1.02
      1.23]). In the multivariate analysis with both exposures included as covariates,
      serum cotinine level was not significantly associated with airflow obstruction
      (ORadj, 1.07 [95% CI, 0.94-1.21]), and no association was seen in children with
      asthma and nonasthmatic children. Prenatal smoking was associated with airflow
      obstruction in children with asthma (ORadj, 2.51 [95% CI, 1.08-5.79]) but not in
      nonasthmatic children (ORadj, 1.08 [95% CI, 0.53-2.18]). CONCLUSIONS: Current TSE
      was not independently associated with airflow obstruction in school-aged
      children. Prenatal TSE was associated with airflow obstruction in children with
      asthma. Repeated studies into potential mediators and confounders of this
      relationship are needed.

PMID- 29037531
TI  - Cytoreductive nephrectomy: A medical oncologist's perspective.
AB  - The role of cytoreductive nephrectomy (CN) was firmly established in the cytokine
      era on the basis of 2 randomized studies employing adjunctive interferon therapy.
      However, systemic therapy for metastatic renal cell carcinoma has evolved
      markedly over the past decade, with targeted therapies representing the standard
      of care in the front-line setting. The preponderance of retrospective data
      generated to date appears to suggest that the benefit of CN is maintained in the
      targeted therapy era. However, these studies are inherently prone to selection
      bias and cannot substitute prospective evidence. Herein, we discuss ongoing
      prospective studies evaluating CN and propose novel strategies to evaluate this
      surgical technique in the context of an evolving therapeutic landscape.

PMID- 29037530
TI  - A structured framework for optimizing surgical quality through process-of-care
      trials.
AB  - Increased national focus has been placed on care delivery processes and their
      effect on health care quality. At the institutional level, investigators are
      increasingly engaged in surgical process-of-care trials that, compared to
      traditional randomized treatment trials, more explicitly control and mitigate
      provider- and system-based risk. Process-of-care trials have the potential to
      improve patient care while also improving the culture of a surgical department,
      hospital, and system.

PMID- 29037532
TI  - Prediction of respiratory collapse among pediatric patients with mediastinal
      tumors during induction of general anesthesia.
AB  - PURPOSE: Fatality resulting from respiratory collapse (RC) during general
      anesthesia (GA) induction in children with mediastinal tumors has been reported.
      We explored potentially useful parameters for predicting the risk of RC based on
      objective imaging results. METHODS: We retrospectively reviewed the records of 31
      patients (median age: 4years; range: 4months-15years) with mediastinal tumors
      treated between 2000 and 2015. Comparing those with RC under GA induction to
      those without (RC group vs. non-RC group), we analyzed a variety of factors that
      might predict respiratory obstruction during GA induction, including our new
      parameter, the standardized tumor volume (STV), which is adapted from the formula
      for the volume of an ellipsoid. RESULTS: All eight patients in the RC group had
      large tumors in the anterior mediastinum, including lymphoma, teratoma, and germ
      cell tumor. The mean STV value of the RC group was significantly larger than that
      of the non-RC group (3.6+/-1.4 vs. 1.4+/-1.0, p=0.006). Using an STV cut-off
      value of 2.5, the sensitivity and specificity for predicting RC under GA
      induction were both 0.86, making STV more useful than previously reported risk
      factors. CONCLUSION: Anterior mediastinal tumors in children can often cause
      airway obstruction under GA induction. Measuring STV can help predict the
      respiratory risk during GA among pediatric patients with anterior mediastinal
      tumors. LEVEL OF EVIDENCE: III.

PMID- 29037534
TI  - Biomechanical comparison of three different plate configurations for comminuted
      clavicle midshaft fracture fixation.
AB  - BACKGROUND: The aim of this study was to compare the fixation rigidity of
      anterior, anterosuperior, and superior plates in the treatment of comminuted
      midshaft clavicle fractures. METHODS: Six-hole titanium alloy plates were
      produced according to anatomic features of fourth-generation artificial clavicle
      models for anterior (group I; n = 14), anterosuperior (group II; n = 14), and
      superior (group III; n = 14) fixation. After plate fixation, 5-mm segments were
      resected from the middle third of each clavicle to create comminuted fracture
      models. Half the models from each group were tested under rotational forces; the
      other half were tested under 3-point bending forces. Failure modes, stiffness
      values, and failure loads were recorded. RESULTS: All models fractured at the
      level of the distalmost screw during the failure torque, whereas several failure
      modes were observed in 3-point bending tests. The mean stiffness values of groups
      I to III were 636 +/- 78, 767 +/- 72, and 745 +/- 214 N ? mm/deg (P = .171),
      respectively, for the torsional tests and 38 +/- 5, 20 +/- 3, and 13 +/- 2 N/mm,
      respectively, for the bending tests (P < .001 for group I vs. groups II and III;
      P = .015 for group II vs. group III). The mean failure torque values of groups I
      to III were 8248 +/- 2325, 12,638 +/- 1749, and 10,643 +/- 1838 N ? mm (P = .02
      for group I vs. II), respectively, and the mean failure loads were 409 +/- 81,
      360 +/- 122, and 271 +/- 87 N, respectively (P = .108). CONCLUSIONS: In the
      surgical treatment of comminuted midshaft clavicle fractures, the fixation
      strength of anterosuperior plating was greater than that of anterior plating
      under rotational forces and similar to that of superior plating.

PMID- 29037535
TI  - Performance of implant sonication culture for the diagnosis of periprosthetic
      shoulder infection.
AB  - BACKGROUND: Diagnosing infection after shoulder arthroplasty can be a challenge
      because of the high prevalence of low-virulence organisms, such as
      Propionibacterium acnes. The purpose of this study was to evaluate the utility of
      implant sonication fluid cultures in the diagnosis of periprosthetic joint
      infection compared with standard culture techniques in patients undergoing
      revision shoulder arthroplasty. METHODS: Routine perioperative testing was
      performed in 53 patients who underwent revision shoulder arthroplasty. In
      addition to routine tissue and fluid culture, the retrieved shoulder implants
      underwent sonication with culture of the sonicate fluid. Diagnostic performance
      of implant sonication culture was determined on the basis of previously defined
      infection criteria and compared with standard intraoperative cultures. RESULTS:
      Of the 53 revision cases that underwent implant sonication fluid culture, 25
      (47%) were classified as infected. Intraoperative culture (tissue and fluid)
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV), and accuracy were 96%, 75%, 77%, 95%, and 85%, respectively. Using a
      cutoff of >20 colony-forming units per milliliter to exclude contaminants, the
      sensitivity, specificity, PPV, NPV, and accuracy of implant sonicate culture were
      56% (P < .001, compared with standard intraoperative cultures), 93% (P = .07),
      88% (P = .4), 70% (P = .02), and 75% (P = .22), respectively. Without use of a
      sonication fluid culture cutoff value, the sensitivity, specificity, PPV, NPV,
      and accuracy of implant sonicate culture were 96% (P = 1.0, compared with
      standard intraoperative cultures), 64% (P = .38), 71% (P = .53), 95% (P = .9),
      and 79% (P = .45). CONCLUSIONS: Implant sonication fluid culture in revision
      shoulder arthroplasty showed no significant benefits over standard intraoperative
      cultures in diagnostic utility for periprosthetic joint infection.

PMID- 29037533
TI  - Continuous tamoxifen delivery improves locomotor recovery 6h after spinal cord
      injury by neuronal and glial mechanisms in male rats.
AB  - No treatment is available for patients with spinal cord injury (SCI). Patients
      often arrive to the hospital hours after SCI suggesting the need of a therapy
      that can be used on a clinically relevant window. Previous studies showed that
      Tamoxifen (TAM) treatment 24h after SCI benefits locomotor recovery in female
      rats. Tamoxifen exerts beneficial effects in male and female rodents but a gap of
      knowledge exists on: the therapeutic window of TAM, the spatio-temporal
      mechanisms activated and if this response is sexually dimorphic. We hypothesized
      that TAM will favor locomotor recovery when administered up-to 24h after SCI in
      male Sprague-Dawley rats. Rats received a thoracic (T10) contusion using the
      MACSIS impactor followed by placebo or TAM (15mg/21days) pellets in a therapeutic
      window of 0, 6, 12, or 24h. Animals were sacrificed at 2, 7, 14, 28 or 35days
      post injury (DPI) to study the molecular and cellular changes in the acute and
      chronic stages. Immediate or delayed therapy (t=6h) improved locomotor function,
      increased white matter spared tissue, and neuronal survival. TAM reduced reactive
      gliosis during chronic stages and increased the expression of Olig-2. A
      significant difference was observed in estrogen receptor alpha between male and
      female rodents from 2 to 28 DPI suggesting a sexually dimorphic characteristic
      that could be related to the behavioral differences observed in the therapeutic
      window of TAM. This study supports the use of TAM in the SCI setting due to its
      neuroprotective effects but with a significant sexually dimorphic therapeutic
      window.

PMID- 29037537
TI  - Validation of two Chinese-version pain observation tools in conscious and
      unconscious critically ill patients.
AB  - OBJECTIVES: To compare the construct validities of the Chinese-versions Critical
      Care Pain Observation Tool and Behavioural Pain Scale as measures of critically
      ill patients' pain by (a) discriminant validation of behavioural scales and vital
      signs (e.g. heart rate and mean arterial pressure) during a non-nociceptive
      procedure (noninvasive blood pressure] assessment) and a nociceptive procedure
      (endotracheal suctioning), (b) criterion validation of behavioural scales and
      vital signs with patients' self-reported pain and (c) testing the interrater
      reliability of both scores. RESEARCH METHODOLOGY/DESIGN: In this crossover,
      observational study, pain responses of 316 critically ill patients (213
      conscious; 103 unconscious) were measured by both the Critical Care Pain
      Observation Tool and the Behavioural Pain Scale scores, vital signs and self
      report (if conscious) during noninvasive blood pressure assessment and
      endotracheal suctioning procedures. Interrater reliability was tested in
      nociceptive procedures of a pilot study on 20 critically ill patients. Data were
      analysed by descriptive statistics, multiple logistic regression analysis and
      receiver-operating characteristic curves. SETTING: A medical intensive care unit
      in a regional teaching hospital in northern Taiwan. RESULTS: Patients' self
      reported pain was predicted by total Critical Care Pain Observation Toolscores
      (odds ratio=1.93, p<0.01) and total Behavioural Pain scores (odds ratio=1.83,
      p<0.01) but not by vital signs after controlling for patients' demographic and
      clinical characteristics. Moreover, Chinese-versions had areas under the receiver
      operating characteristic curve of 76.4% and 73.1%, respectively, indicating good
      ability to detect pain. CONCLUSIONS: The Chinese-versions of the Critical care
      Pain Observation Toll and Behavioural Pain Score have good construct validity and
      can sensitively discriminate when critically ill patients experience pain or no
      pain.

PMID- 29037536
TI  - Open reduction and internal fixation for nonunion of extra-articular distal
      humeral fractures in patients 70 years and older.
AB  - HYPOTHESIS: The study purpose was to report the clinical and radiologic outcomes
      of osteosynthesis by open reduction and internal fixation for nonunion of extra
      articular distal humeral fractures in patients aged 70 years or older. MATERIALS
      AND METHODS: This retrospective study included 28 patients who received
      osteosynthesis treatment between March 2010 and December 2015. Primary
      conservative treatment had failed in all patients. All surgical procedures were
      performed via the posterior approach without olecranon osteotomy and with the use
      of double-locking plates for each column. RESULTS: The mean patient age was 72
      years, and surgical procedures were performed a mean of 7.6 months after injury.
      Preoperatively, extension-flexion was 32 degrees  to 101 degrees  and forearm
      pronation-supination was 74 degrees  to 47 degrees . The mean visual analog scale
      score was 4; the mean Mayo Elbow Performance Score was 50; and the mean
      Disabilities of the Arm, Shoulder and Hand score was 58. All cases showed proper
      union after a mean of 5.2 months. At the final follow-up examination, the
      extension-flexion and rotation arcs had improved significantly (to 20 degrees  to
      124 degrees  and to 80 degrees  to 66 degrees , respectively; both P < .001), and
      all clinical scores were satisfactory (visual analog scale score, 1; Mayo Elbow
      Performance Score, 65; and Disabilities of the Arm, Shoulder and Hand score, 24;
      all P < .001). Ulnar nerve transposition was performed in 7 patients, and no
      distinct ulnar nerve symptom was observed in any patient at the final follow-up
      examination. CONCLUSIONS: We consider osteosynthesis by open reduction and
      internal fixation as a recommended option for extra-articular distal humeral
      fractures in elderly patients aged 70 years or older in whom conservative
      treatment has failed.

PMID- 29037538
TI  - Glucose trajectories in cystic fibrosis and their association with pulmonary
      function.
AB  - BACKGROUND: The prevalence of cystic fibrosis-related diabetes is increasing.
      This condition is potentially responsible for respiratory decline. METHODS: At
      inclusion, then yearly (over three years), 111 children and 117 adults with
      cystic fibrosis had oral glucose tolerance and insulin tests at one (G1) and 2h
      (G2). KmL analysis identified homogeneous G1 and G2 glucose trajectories. A
      linear mixed model quantified the relationships between trajectories and FEV1
      changes. RESULTS: In children, there were three G1 and four G2 trajectories and
      FEV1 decrease was not significantly different between G1 or G2 trajectories. In
      adults, two G1 and four G2 trajectories were identified and FEV1 change was
      estimated at -0.85/year (95% CI: [-1.54; -0.17], p=0.01) whatever the G1
      trajectory and found significantly faster in the high and increasing G2
      trajectory (-2.1/year, [-3.9; -0.2], p=0.03). CONCLUSIONS: In case of persistent
      G2 abnormality, physicians should be alert for clinical deterioration and
      intensify patient surveillance.

PMID- 29037539
TI  - Outstanding female cancer research paper awards of the 2016 Taiwan Association of
      Obstetrics and Gynecology and Hsu Chien-Tien Cancer Foundation.

PMID- 29037540
TI  - Do pregnant women with asymptomatic bacteriuria need treatment?

PMID- 29037541
TI  - Zika virus: An emerging challenge for obstetrics and gynecology.
AB  - Microcephaly is a rare birth defect, however, the re-emerging mosquito and sexual
      transmitted flavivirus, Zika virus (ZIKV), had changed the situation and caused
      an urgent challenge for the obstetrics and gynecology. This review will brief
      summarize the epidemiology and virology of ZIKV. And compared the animal models
      that had developed for the ZIKV infections. These animal models will be benefit
      for the development of vaccines and anti-ZIKV drugs. Furthermore, the genes that
      are involved in the causation of microcephaly were also summarized. Finally, the
      Wnt signal is critical for the brain development as well as innate immune
      response. Based on previous literatures, we proposed that ZIKV-induced
      microcephaly might result from the influence of Wnt/beta-catenin signaling
      pathway through the regulation of miRNA-34.

PMID- 29037542
TI  - Preeclampsia: A review of the pathogenesis and possible management strategies
      based on its pathophysiological derangements.
AB  - This review is divided into three parts. The first part briefly describes the
      pathogenesis of preeclampsia. This is followed by reviewing previously reported
      management strategies of the disease based on its pathophysiological
      derangements. Finally, the author defines the safe and acceptable
      methods/medications that may be used to 'prevent' preeclampsia (in high risk
      patients) and those that may be used to 'treat' preeclampsia (meant to prolong
      the pregnancy in patients with established preeclampsia). The review concludes
      that multi-center trials are required to include multiple drugs in the same
      management protocol.

PMID- 29037543
TI  - Amniopatch treatment for preterm premature rupture of membranes before 23 weeks'
      gestation and factors associated with its success.
AB  - OBJECTIVE: The purpose of this study is to investigate the factors associated
      with successful amniopatch treatment in patients with iatrogenic preterm
      premature rupture of membranes (iPPROM) or spontaneous PPROM (sPPROM) before 23
      weeks' gestation. MATERIALS AND METHODS: This cohort study included 28 women who
      received amniopatch treatment due to iPPROM or sPPROM at 15-23 weeks' gestation.
      Patients' clinical characteristics before performing the amniopatch, factors
      associated with the procedure, pregnancy and neonatal outcomes were compared
      between the iPPROM and sPPROM groups, and also between the successful and failed
      groups. RESULTS: The amniopatch was successful in 6 of 28 patients (21.4%) with a
      success rate of 36.4% (4/11) and 11.8% (2/17) in the iPPROM group and sPPROM
      group (P = 0.174), respectively. The success group had a longer PPROM-to-delivery
      interval, fewer cases of clinical chorioamnionitis, larger birth weight, and
      lower neonatal intensive care unit admission rate than the failed group. The
      success rate of amniopatch procedure was proportional to maximal vertical pocket
      prior to procedure, which showed statistically significant association (adjusted
      odds ratio: 3.62, 95% confidence interval: 1.16-11.31, P = 0.027). CONCLUSION:
      The amniopatch treatment success rate was higher in the iPPROM group than the
      sPPROM group, but was not statistically significant. The neonatal outcome was
      more favorable when the amniopatch was successful. However, the only predictive
      factor associated with successful amniopatch was a larger amniotic fluid volume
      before the procedure.

PMID- 29037544
TI  - Effects of pushing techniques during the second stage of labor: A randomized
      controlled trial.
AB  - OBJECTIVE: Spontaneous pushing is a method that is used in the management of the
      second stage of labor and suggested to be more physiological for the mother and
      infant. The present study aims to evaluate the effects of pushing techniques on
      the mother and newborn. MATERIALS AND METHODS: This randomized prospective study
      was performed between June 2013-March 2014 in a tertiary maternity clinic in
      Istanbul. 80 low risk, nulliparous cases were randomized to pushing groups.
      Valsalva pushing group was told to hold their breath while pushing. No visual
      verbal instructions were given to spontaneous pushing group and they were
      encouraged to push without preventing respiration. Demographic data, second stage
      period, perineal laceration rates, fetal heart rate patterns, presence of
      meconium stained amniotic liquid, newborn APGAR scores, POP-Q examination and Q
      tip test results were evaluated in these cases. RESULTS: The second stage of
      labor was significantly longer with spontaneous pushing. Decrease in Hb levels in
      valsalva pushing group was determined to be higher than spontaneous pushing
      group. An increased urethral mobility was observed in valsalva pushing group.
      CONCLUSIONS: Although the duration of the second stage of labor was longer
      compared to valsalva pushing technique, women were able to give birth without
      requiring any verbal or visual instruction, without exceeding the limit value of
      two hours and without affecting fetal wellness and neonatal results.

PMID- 29037545
TI  - Perineal length among Vietnamese women.
AB  - OBJECTIVE: Vietnamese clinicians routinely perform episiotomies in the belief
      that 3rd-4th degree tears may be prevented, based partly on the view that
      Vietnamese women have a short perineal length that puts them at increased risk of
      tears. However, there is no evidence to suggest Vietnamese women have a short
      perineum compared with other populations. We aimed to determine the mean perineal
      length among Vietnamese women in early labor and in the second stage, and to
      compare this to findings from similar studies in other populations. MATERIALS AND
      METHODS: We undertook an observational study in a tertiary obstetric hospital in
      Vietnam from October 2014 to June 2015. Pregnant women who presented in early
      labor with a live singleton cephalic presentation at >=37 weeks gestation were
      eligible. Perineal length was measured early in the 1st stage of labor (<=4 cm
      dilation) and in 2nd stage of labor (10 cm dilation). Mean perineal length was
      compared to other populations using t-tests. RESULTS: Of 395 women, 159 (40.3%)
      were nulliparous and 236 (59.8%) multiparous. Overall the mean perineal length in
      early labor was 3.4 cm (+/-0.4), and did not differ by parity. Mean perineal
      length among Vietnamese women was significantly shorter (P < 0.001) than other
      populations (means 3.8-4.6 cm). Among 365 women who reached 2nd stage the mean
      perineal length was 4.3 cm (+/-0.6). CONCLUSION: The perception that Vietnamese
      women have a relatively shorter perineal length appears to have some basis and
      outcomes reported from episiotomy trials may not be generalizable to Vietnamese
      women.

PMID- 29037546
TI  - Acceptance towards giving birth to a child with beta-thalassemia major - A
      prospective study.
AB  - OBJECTIVE: To explore the acceptance of pregnant Chinese women on giving birth to
      a child with beta-thalassemia major. MATERIALS AND METHODS: Women's acceptance on
      having a child with beta thalassemia major was assessed using standard gamble
      metrics during an interviewer-administered survey on 309 women recruited in the
      antenatal clinic. Utility scores were determined and the association with
      sociodemographic factors was assessed. RESULTS: The median utility score for
      having a child with beta-thalassemia major was 0.5 (0-0.65). Women having either
      higher educational level or family income had significantly higher utility scores
      (P < 0.05) corresponding to a higher acceptance. During the interview 59.9%
      participants indicated that they would elect to undergo a termination of
      pregnancy if their fetus was diagnosed with beta-thalassemia major but 26.5%
      participants were unable to decide what action they would take. CONCLUSION: Many
      Chinese pregnant women are ambivalent about giving birth to a baby with beta
      thalassemia major. Women with higher educational level or higher family income
      had a higher acceptance towards the condition.

PMID- 29037547
TI  - Prenatal diagnosis of umbilical cord cyst: Clinical significance and prognosis.
AB  - OBJECTIVE: Clarify the prognosis of the prenatal ultrasound diagnosis of
      umbilical cord cysts at any gestation trimester and to assess the ultrasound
      findings and chromosomal alterations associated to this entity. MATERIALS AND
      METHODS: Between 2003 and 2015 a multicenter study was carried out, collecting,
      in five centers in Spain, the associated findings and perinatal outcomes of 27
      cases of umbilical cord cysts, regardless of gestational age of diagnosis. A
      bibliographic review was conducted to identify previous studies in order to
      compare them with our data. RESULTS: In our sample, the prognosis of this finding
      and the neonatal outcome, when isolated, is favorable, regardless of gestational
      age at diagnosis, multiple or unique presentation or vanishing or persistent
      cysts. CONCLUSIONS: It is important to properly assess the umbilical cord cyst
      and when is diagnosed, it is recommended to conduct a meticulous ultrasound
      examination searching for other associated malformations. In our study the
      prognosis of this finding seems to be favorable when isolated. Also, there is no
      relation between prognosis and gestation weeks at diagnosis. On the other hand,
      when we find this entity with associated anomalies, it is recommended to assess
      the need to carry out a karyotype.

PMID- 29037548
TI  - Pathological discrepancy between colposcopic directed cervical biopsy and Loop
      Electrosurgical-Excision Procedures (LEEPs) in patients with biopsies proven high
      grade cervical intraepithelial neoplasia.
AB  - OBJECTIVE: To determine the prevalence of patients with CIN1 or less from LEEP
      specimens in patients with colposcopic biopsy proven CIN2 or 3. MATERIALS AND
      METHODS: This study was a retrospective-descriptive chart review. Clinical data
      were retrieved from medical records of women with CIN2 or 3 from colposcopic
      biopsy who subsequently underwent LEEP procedure between 2004 and 2014. All
      pathological slides were reviewed by the gynecologic pathologist. Statistical
      analyses were performed. RESULTS: Of 210 patients, 14 patients were excluded from
      the study. 196 patients were in eligible criteria and data were analyzed. There
      were 32 patients (16.3%) with CIN1 or less from LEEP specimens who previously had
      colposcopic biopsies proven CIN2 or 3. Only CIN2 from biopsy was the
      statistically significant risk factor of CIN1 or less in LEEP specimens. Odds
      ratio was 10.45 (95% confidence interval: 3.28-33.33, P < 0.001). CONCLUSION: The
      prevalence of patients with CIN1 or less from LEEP specimens who previously had
      colposcopic biopsies proven CIN2 or 3 was 16.3%. CIN2 from biopsy was the
      statistically significant risk factor of CIN1 or less in LEEP specimens.

PMID- 29037549
TI  - Long-term outcome of pregnancy complicating with severe aplastic anemia under
      supportive care.
AB  - OBJECTIVES: Pregnancy associated with aplastic anemia (AA) is a rare and
      heterogeneous disorder. We aimed to identify and evaluate the maternal and
      pregnant outcomes of pregnancy-associated severe AA treated with supportive care.
      MATERIALS AND METHODS: A 25-year retrospective study was conducted at in a single
      center between 1990 and 2014 with pregnancy associated severe AA. In addition,
      relevant published cases of antenatally diagnosed pregnancy-associated severe AA
      after 1990 were identified by PubMed. The main goal was to determine the impact
      of various risk factors on maternal and fetal outcomes. RESULTS: 15 women with 18
      pregnancies were enrolled. With addition of the published reports in literature,
      a total of 36 cases were included for reference review. Univariate analysis
      showed that low platelet counts (<2.0 * 109/L), bone marrow hypocellularity
      (<25%), and late diagnosis during pregnancy were predictors of poor maternal
      outcomes (P < 0.05). The complication rate of pregnancy outcomes was 53.3%,
      including preterm delivery, small gestational age (SGA), preterm premature
      ruptured of membranes (PPROM) and preeclampsia. CONCLUSIONS: This study
      identified the risk factors of mortality and morbidity in pregnant women with
      severe AA, as well as the obstetrical complications associated with neonatal
      outcome.

PMID- 29037550
TI  - Temporal availability of obstetrics and gynecology clinics in Taiwan: A
      nationwide survey.
AB  - OBJECTIVE: Obstetrician-gynecologists are the main providers of women's
      healthcare. However, workforce shortages and excessive workloads among these
      providers have been encountered in many countries. While most past studies on
      this subject have investigated the spatial distribution of obstetrics-gynecology
      clinics, few have focused on their temporal availability, especially on the
      national level. MATERIALS AND METHODS: The weekly opening time schedules (divided
      into morning, afternoon, and evening sessions) of all obstetrics-gynecology
      clinics in Taiwan were extracted from the web site of Taiwan's National Health
      Insurance Administration in July 2015. The numbers of open sessions were then
      analyzed and stratified by urbanization level and practice type. RESULTS: Among
      742 obstetrics-gynecology clinics in Taiwan, 521 were located in urban areas, 194
      in suburban areas, and 27 in rural areas. The numbers of open sessions per week
      in suburban areas were higher than those in urban and rural areas (16.7 +/- 2.6
      vs. 15.9 +/- 3.1 and 15.9 +/- 2.7). Group practices had more open sessions per
      week than solo practices (16.8 +/- 2.8 vs. 15.8 +/- 3.0). With respect to after
      hours services in rural areas, only two rural obstetrics-gynecology clinics
      remained open on Sunday mornings, while none remained open on Sunday afternoons
      and evenings. CONCLUSION: Obstetrics-gynecology clinics in Taiwan offered great
      temporal availability. In addition to the remarkable urban-rural disparity in the
      distribution of obstetrics-gynecology clinics, the availability of services on
      Sundays in rural areas demands special attention.

PMID- 29037551
TI  - Ductus venosus Doppler and the postnatal outcomes of growth restricted fetuses
      with absent end-diastolic blood flow in the umbilical arteries.
AB  - OBJECTIVE: We aimed to evaluate the outcomes of growth-restricted fetuses with
      absent end-diastolic velocity in the umbilical arteries (UA-AEDV), and
      investigate the relationship between Doppler flow velocity waveforms in the
      ductus venosus (DV) and the clinical features. MATERIALS AND METHODS: This was a
      retrospective study of growth-restricted fetuses diagnosed with UA-AEDV delivered
      at our institution between 2013 and 2015. The time from diagnosis of UA-AEDV to
      delivery, postnatal survival, and developmental prognoses were the primary
      outcomes. The time lag between the occurrence of UA-AEDV and an abnormal increase
      in the DV pulsatility index (DV-PI) were investigated. We also examined the
      correlation between the DV-PI values immediately before birth and umbilical cord
      arterial pH at birth. RESULTS: The median gestational age at birth among the 18
      subjects was 28+2 (24+0-34+6) weeks, and the observation period between the first
      detection of UA-AEDV and delivery ranged from 0 to 35 days with a median of 8
      days. Among the 18 infants, 15 (83%) survived, among whom 2 were diagnosed with a
      developmental disability. Gestational age at delivery was significantly lower in
      the poor outcome group. A positive correlation (correlation coefficient, 0.68)
      was observed between the umbilical artery pH and the last measured DV-PI.
      CONCLUSION: The time interval from initial detection of UA-AEDV to delivery is
      highly variable, and it is reasonable to manage these growth-restricted fetuses
      with UA-AEDV expectantly with careful surveillance for fetal well-being.
      Specifically, Doppler DV analysis is clinically valuable for their evaluation.

PMID- 29037552
TI  - The impact of prenatal group B streptococcus screening as a national health
      policy in Taiwan.
AB  - OBJECTIVE: There was no national data on group B streptococcus (GBS) infections
      in Taiwan. Until 2012, when prenatal GBS screening was introduced to obstetric
      practices as a national health policy aimed at reducing neonatal GBS infections.
      The purpose of this study was to examine the impact of this national health
      policy on the incidence of maternal GBS colonization and neonatal GBS infection
      rate. Relatedly, the clinical characteristics of neonatal GBS infection were
      investigated to determine the correlations between the incidence of maternal GBS
      colonization and the neonatal GBS infection rate. MATERIALS AND METHODS: This
      population-based nationwide study used data for 2012-2013 from the National
      Health Insurance Research Database of Taiwan. A total of 789 newly diagnosed
      pregnant women with genital GBS infection were recruited. RESULTS: The maternal
      GBS screening rate was 93.2%. The maternal colonization rate of GBS was around
      8.2%, and the incidence of neonatal GBS infection was 22.6%. The data indicate
      that no sepsis was developed in any of the cases, while fever was found in 3
      cases (3/179, 1.7%) and UTI was found in 1 case (1/179, 0.6%). CONCLUSIONS: We
      conclude that a policy calling for universal maternal rectovaginal cultures for
      GBS with intrapartum antibiotic prophylaxis is a good national policy for
      reducing morbidity due to GBS infections in neonates in Taiwan.

PMID- 29037553
TI  - Association of miR-146a rs2910164 and miR-222 rs2858060 polymorphisms with the
      risk of polycystic ovary syndrome in Iranian women: A case-control study.
AB  - OBJECTIVE: Today, many single nucleotide polymorphisms in microRNA genes are
      known to alter the microRNA expression levels or processing causing
      susceptibility of several human diseases. The present study aimed to investigate
      the association of microRNA-146a (rs2910164) and microRNA-222 (rs2858060)
      polymorphisms with susceptibility to polycystic ovary syndrome (PCOS) in an
      Iranian population. MATERIALS AND METHODS: This case-control study was performed
      on 205 patients with PCOS and 205 normal women as the control group. After DNA
      extraction, Tetra-amplification refractory mutation system polymerase chain
      reaction (T-ARMS-PCR) was used to detect the polymorphisms. The association
      between genotypes and the risk of PCOS was examined by odds ratios (OR) and 95%
      of confidence intervals (CIs). RESULTS: Our results showed that there are
      significant differences in CG genotype frequencies between case and control
      groups regarding miR-146a rs2910164 polymorphism (OR = 2.03, CI = 1.3-3, P =
      0.001). In a dominant model for the C allele, CC + CG genotypes were associated
      with PCOS risk (OR = 2, 95% CI = 1.3-2.9, P = 0.001) and the C allele increased
      the risk of PCOS (OR = 1.6, 95% CI = 1.1-2.1, P = 0.004). Furthermore, a positive
      association was observed between miR-222 CG genotype and the risk of PCOS (OR =
      2.2, 95% CI = 1.1-4.1, P = 0.02). These results were evident after adjustment for
      age and body mass index. CONCLUSION: The present results suggest that the miR
      146a rs2910164 and miR-222 rs2858060 polymorphisms are associated with an
      increased risk of PCOS. Therefore, both polymorphisms could play an important
      role as a genetic risk factor for development of PCOS in the Iranian population.

PMID- 29037554
TI  - The role of resveratrol on full - Thickness uterine wound healing in rats.
AB  - OBJECTIVE: Healing of the uterus after cesarean section and myomectomy operation
      is clinically important. In this study, we aimed to investigate the effects of
      resveratrol (3,5,4'-o-trihydroxystilbene) on the wound healing process of the
      uterus in rats treated with resveratrol following full thickness injury of the
      uterus. MATERIALS AND METHODS: Twenty-one female wistar albino rats were divided
      randomly into three groups (1) control group with no intervention (2) injury
      group with uterine full thickness injury (3) resveratrol group with uterine full
      thickness injury and treated with resveratrol. Resveratrol was injected by oral
      gavage at the doses of 0.5 mg/kg/day for 30 days following uterine full thickness
      injury. Vascular endothelial growth factor (VEGF) and platelet-derived growth
      factor (PDGF) distributions were assessed using the immunohistochemical methods
      in tissue and ELISA methods in the tissue homogenate. Glutathione peroxidase
      (GPx) and superoxide dismutase (SOD) activities were evaluated with colorimetric
      method and malondialdehyde (MDA) levels also were measured using high performance
      liquid chromatography in the tissue homogenate. The effects of resveratrol on the
      uterine histology also were evaluated histologically with the light microscopy.
      RESULTS: Histological evaluation and immunohistochemical evaluations showed that
      treatment with a resveratrol significantly increased the thickness of the uterine
      wall and VEGF expression and decreased expression PDGF during wound healing.
      Biochemically, GPx and SOD activities were increased significantly after
      treatment with resveratrol. Additionally, resveratrol administration decreased
      MDA levels. CONCLUSION: These results showed that the antioxidant effects of
      resveratrol has been shown to have a positive influence on wound healing of the
      uterus.

PMID- 29037555
TI  - A genome-wide comparison of mesenchymal stem cells derived from human placenta
      and umbilical cord.
AB  - OBJECTIVE: The human umbilical cord and placenta have been considered as
      attractive alternative sources for noninvasive isolation of human mesenchymal
      stem cells (hMSCs). Different sources of MSC may have individual differentiation
      potential and phenotype. In this study, we compared the genome-wide expression
      data of umbilical cord and placenta derived hMSCs to identify specific
      differential expression genes (DEGs) and corresponding functions. MATERIALS AND
      METHODS: We collected human placental tissues and umbilical cord from healthy
      full-term placenta (n = 17). The genome-wide gene expression data of hMSCs were
      used to analyze and compare with that of fibroblasts. We identified the
      differential expression genes (DEGs) based on the Student's t-test and one-way
      ANOVA. RESULTS: According to the DEGs of umbilical cord and placenta, we used the
      Venn diagram to evaluate the consistence and specific genes. There are 390
      umbilical cord specific DEGs which functions are related to movement of sub
      cellular component. Then, the DEGs derived from placenta have two major clusters
      (i.e., placenta-specific (AM-CM-specific) and UC-like (UC-CD-specific)). 247
      placenta-specific DEGs are down-regulated and involved in cell communication. 278
      UC-like genes are up-regulated and are involved in the cell cycle, cell division,
      and DNA repair process. Finally, we also identified 239 umbilical cord-placenta
      consistence DEGs. According to the umbilical cord-placenta consistence DEGs, 175
      genes are down-regulated and involved in cell death, cell growth, cell
      developmental processes. CONCLUSION: We identified the consistence and specific
      DEGs of human placenta and umbilical cord based on the genome-wide comparison.
      Our results indicated that hMSCs derived from umbilical cord and placenta have
      different gene expression patterns, and most of specific genes are involved in
      the cell cycle, cell division, cell death, and cell developmental processes.

PMID- 29037556
TI  - Transcutaneous electrical acupoint stimulation (TEAS) treatment improves
      pregnancy rate and implantation rate in patients with implantation failure.
AB  - OBJECTIVE: Although major advances have greatly improved the outcomes of assisted
      reproductive technology in the last two cascades, there remains significant
      difficulty in achieving pregnancy for many patients even after repeated attempts
      of IVF. Interestingly, recent studies have shown that transcutaneous electrical
      acupoint stimulation (TEAS) can improve the reproductive outcomes of select IVF
      patients. To determine the utility of TEAS in improving IVF outcomes in patients
      with a history of implantation failure, we conducted a retrospective study of
      clinical outcomes of women, who had a prior history of unsuccessful pregnancy
      outcome after IVF-embryo transfer (IVF-ET), following TEAS treatment. MATERIALS
      AND METHODS: A total of 25 patients, who had failed to conceive after multiple
      IVF cycles in which good embryos were transferred, received noninvasive low
      frequency TEAS treatment prior to and during an IVF-ET cycle. The clinical
      outcomes, including biochemical pregnancy rate, clinical pregnancy rate and
      implantation rate, were compared to those of prior cycles which received only
      standard IVF treatment. RESULTS: Analysis of reproductive outcomes showed that
      implantation rate and clinical pregnancy rate increased significantly in IVF
      cycles that included the TEAS treatment when compared to prior cycles that
      received only the standard IVF treatment in this cohort of patients. CONCLUSIONS:
      This surprising finding indicated that TEAS treatment is a promising technique to
      improve reproductive outcomes in difficult cases of IVF-ET. Because TEAS
      treatment is noninvasive and has high reproducibility, and can be applied with
      limited training, further refinement of this procedure would not only
      substantiate the beneficial effects of TEAS, but also allow the technique to be
      more effective and reproducible.

PMID- 29037557
TI  - Prenatal diagnosis of isochromosome 20q in a fetus with vertebral anomaly and
      rocker-bottom feet.
AB  - OBJECTIVE: Isochromosome of the long arm of chromosome 20 (i(20q)) is a rare
      structural abnormality in prenatal diagnosis. Thirty prenatal cases of mosaic
      i(20q) have been reported, among which only four are associated with fetal
      malformations. We describe a new prenatal case of i(20q) with fetal
      malformations. MATERIALS AND METHODS: We also observed a discrepancy between
      uncultured and cultured amniotic fluid cells by using conventional cytogenetic,
      fluorescence in situ hybridization and array-SNP analysis. RESULTS: The short arm
      deletion of chromosome 20 arising from the isochromosome encompassed two
      candidate genes PAX1 and JAG1 involved in cranio-facial and vertebral
      development. CONCLUSION: The data would allow establishing a phenotype-genotype
      correlation. Thus, we proposed to define a recognizable syndrome combining cranio
      facial dysmorphism, vertebral bodies' anomalies, feet and cerebral malformations.

PMID- 29037558
TI  - Monozygotic twins discordant for trisomy 21: Discussion of etiological events
      involved.
AB  - OBJECTIVE: To elucidate the etiologies of discordant trisomy 21 in monozygotic
      twin pregnancy. CASE REPORT: A monochorionic diamniotic twin pregnancy with
      hydrops and cleft lip (twin 1) found in one fetus presented at gestational age of
      17 weeks. Amniotic fluid karyotyping showed nonmosaic trisomy 21 in twin 1 (47,
      XY, +21 [20]) and a normal karyotype in twin 2 (46, XY [20]). Short tandem repeat
      (STR) polymorphism markers revealed that the two fetuses were monozygotic, and
      the two chromosomes 21 were maternal isodisomy in the trisomy fetus. The
      chromosomal constitution of placentas in the territory of trisomy 21 cotwin was
      47, XY, +21 [20] and was a mosaic 47, XY+21 [12]/46, XY [8] in the normal
      karyotyped twin. CONCLUSION: Our case of monozygotic twin with discordant trisomy
      21 might start with a prezygotic maternal meiosis II non-disjunction error-caused
      trisomy 21 zygote, and after twinning, one remained trisomy 21, and the other
      twin underwent trisomy rescue and became a mosaic trisomy 21 in morula or early
      blastocyst stage before the formation of pre-embryo, which subsequently resulted
      in mosaic trisomy 21 of the placental tissue and normal chromosomal constitution
      of the fetus.

PMID- 29037559
TI  - Noninvasive prenatal diagnosis for X-linked disease by maternal plasma sequencing
      in a family of Hemophilia B.
AB  - OBJECTIVE: To apply a Hidden Markov Model to test Hemophilia B in a fetus by
      maternal plasma sequencing only employing proband and maternal haplotypes. CASE
      REPORT: A family at risk for Hemophilia B was recruited in this study. We
      performed genetic diagnosis on the proband using our targeted capture system
      (containing F9 gene coding region, highly heterozygous SNPs and a 13-kb
      chromosome Y specific region), and revealed a causative F9 gene mutation
      (c.190T>C, p.Cys64Arg). Maternal plasma cell-free DNA obtained at 8 weeks of
      gestation was targeted-captured and sequenced using the customized system. The
      fetus inherited the F9 (c.190T>C, p.Cys64Arg) mutation according to the Hidden
      Markov Model. The mother continued the pregnancy. CONCLUSIONS: This study is the
      first report of a haplotype-based approach in NIPD of Hemophilia B. With further
      evaluation, this method might be useful for NIPD of Hemophilia B and for other X
      linked single-gene disorders.

PMID- 29037560
TI  - Application of non-invasive prenatal testing in late gestation in a pregnancy
      associated with intrauterine growth restriction and trisomy 22 confined placental
      mosaicism.
AB  - OBJECTIVE: We present the application of non-invasive prenatal testing (NIPT) in
      late gestation in a pregnancy associated with intrauterine growth restriction
      (IUGR) and trisomy 22 confined placental mosaicism (CPM). CASE REPORT: A 35-year
      old pregnant woman underwent chorionic villus sampling (CVS) at 12 weeks of
      gestation. The pregnancy was conceived by in vitro fertilization and
      intracytoplasmic sperm injection. CVS revealed a karyotype of 47,XY,+22 in all of
      15 cultured chorionic villi cells. Array comparative genomic hybridization
      analysis on uncultured chorionic villi revealed a result consistent with trisomy
      22. The woman underwent amniocentesis at 17 weeks of gestation. Amniocentesis
      revealed a karyotype of 46,XY in all 20 colonies of cultured amniocytes.
      Additional polymorphic DNA marker analysis excluded uniparental disomy 22. The
      parental karyotypes were normal. Prenatal ultrasound at 23 weeks of gestation
      revealed fetal retrognathia, IUGR and a calcified placenta. NIPT at 27 weeks of
      gestation using maternal plasma cell-free DNA analysis showed a chromosome Z
      score of 5.74 for chromosome 22 (the Z-score for each pair of chromosomes is
      defined as "increased" if >3), indicating an abnormal placenta with trisomy 22
      CPM leading to IUGR in the fetus. At 36 weeks of gestation, a 1754-g male fetus
      was delivered with cleft palate and imperforate anus but no other phenotypic
      abnormalities. The cord blood had a karyotype of 46,XY (40/40 cells), the
      umbilical cord had a karyotype of 47,XY,+22[9]/46,XY[31], and the placental
      tissues had a karyotype of 47,XY,+22[15]/46,XY[25]. CONCLUSION: NIPT in late
      gestation is useful in detection of placental abnormality associated with CPM and
      IUGR but a normal karyotype at amniocentesis.

PMID- 29037561
TI  - Repeated pregnancy with concomitant presence of ovarian teratoma: A case report
      and literature review.
AB  - OBJECTIVE: Benign mature teratoma during pregnancy is common, mostly discovered
      incidentally by antenatal sonography. However, repeated pregnancy coincident with
      ovarian mature teratoma is rarely reported. The cases of teratoma with rapid
      growing characteristics are even more unique. CASE REPORT: A 17-year-old woman
      was pregnant at 6 weeks of gestation with a left ovarian teratoma. She underwent
      artificial abortion followed by surgical removal of the teratoma. However, eleven
      years after the surgery, a right ovarian teratoma was found incidentally by
      antepartum sonography at 21 weeks of gestation. The right ovarian teratoma
      developed uneventfully, with rapid growth during pregnancy. Abdominal delivery at
      term was accomplished without any complication. CONCLUSION: Younger patients and
      patients with bilateral or large size dermoid cysts should be followed up
      closely. Further studies are needed for better understanding of its natural
      clinical course and the mechanism of progression. The treatment options should be
      made individually, weighing the risks of torsion, rupture, or obstruction of
      labor versus the potential for unnecessary surgical risk to mother and fetus.

PMID- 29037562
TI  - Dandy-Walker syndrome with duplex kidney abnormalities in trisomy 18 - A rare
      case report.
AB  - OBJECTIVE: Trisomy 18 is one of the major numerical chromosomal disorders. The
      incidence of trisomy 18 is approximately one in 6000 live births. Dandy-Walker
      malformation (DWM) is the most common congenital malformation of the cerebellum,
      with an incidence of about one in 5000 live births. The incidence of trisomy 18
      associated with DWM is rare and long-term survival rate is very low. CASE REPORT:
      A case involving a 39-year-old pregnant female with a case of trisomy 18
      associated with DWM. CONCLUSION: The incidence of trisomy 18 associated with DWM
      is rare, and our report presents an unusual case that supplements our knowledge
      of this condition. We report a case involving a 39-year-old pregnant female with
      a case of trisomy 18 associated with Dandy-Walker malformation (DWM). Fetal
      ultrasonography showed hypoplasia of the cerebellar vermis and dilatation of the
      fourth ventricle and was characterized by an enlarged posterior fossa. Fetal
      magnetic resonance imaging showed inferior vermian hypoplasia and a large
      posterior fossa cyst communicating with the fourth ventricle causing high
      insertion of the torcular herophili, which was compatible with DWM. Furthermore,
      the karyotyping report revealed trisomy 18. The incidence of trisomy 18
      associated with DWM is rare, and our report presents an unusual case that
      supplements our knowledge of this condition.

PMID- 29037563
TI  - Management of pregnancy in pancreas alone transplant recipient complicated with
      stage-4 chronic renal insufficiency and superimposed pre-eclampsia: Case report
      and literature review.
AB  - OBJECTIVE: With the prolonged life expectancy in solid organ transplant
      recipients, their quality of life and fertility desire become of particular
      concern. Pregnancy in pancreas-alone transplantation, although rare and
      complicated to manage, is not impossible anymore. We here report such a case with
      literature review to address this issue. CASE REPORT: A 29-year-old, primigravida
      patient with underlying stage 4 chronic renal insufficiency and type 1 diabetes
      mellitus post pancreas-alone transplantation 5 years prior to her initial visit
      consulted our service. Antepartum care with intensive monitoring of blood
      pressure, renal function, and tacrolimus serum concentration were given.
      Successful maternal and fetal outcomes are presented here. CONCLUSION: Child
      bearing in solid organ transplantation recipients has become more promising
      nowadays, even for a difficult case of pancreas-alone transplant recipient
      complicated with chronic renal insufficiency and superimposed pre-eclampsia.
      Thorough antepartum counseling and cautious monitoring of maternal, fetal and
      graft conditions by multidisciplinary specialties are key to favorable pregnancy
      outcomes.

PMID- 29037564
TI  - Prenatal diagnosis of low-level mosaicism for trisomy 21 with rare karyotype
      detected by noninvasive prenatal testing.

PMID- 29037566
TI  - Responses to the concern raised by Dr. Shigeki Matsubara.

PMID- 29037565
TI  - Serous carcinoma arising from adenomyosis.

PMID- 29037567
TI  - Perspective of Taiwan's experience in the management of meconium peritonitis.

PMID- 29037568
TI  - Granulosa cell tumor of ovary: Perspective of Taiwan.

PMID- 29037569
TI  - Poly(ADP-ribose) polymerase (PARP) inhibitors and ovarian cancer.

PMID- 29037570
TI  - Trace elements and arsenic speciation in tissues of tube dwelling polychaetes
      from hydrothermal vent ecosystems (East Pacific Rise): An ecological role as
      antipredatory strategy?
AB  - Hydrothermal vent systems are inhabited by dense benthic communities adapted to
      extreme conditions such as high temperature, hydrogen sulphide (H2S) and elevated
      fluxes of metals. In the present work, a wide range of trace elements (Ag, Al,
      As, Ba, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Sb, Se, V and Zn) were measured in
      tissues of three tube dwelling annelids, Alvinella pompejana, Alvinella caudata
      and Riftia pachyptila, which colonize distinct habitats of the East Pacific Rise
      (EPR) at 2500 m depth. Metals concentrations in alvinellids were often 2-4 orders
      of magnitude higher than those commonly found in marine organisms, while much
      lower values were observed in the vestimentiferan polychaete. Mobility of trace
      elements was further characterized in tissues of A. pompejana where metals
      appeared mostly in insoluble forms, i.e. associated with hydrated oxides and
      sulphides. Arsenic was mainly present in a weakly insoluble form and with
      concentrations in the branchial tentacles of alvinellids, approximately 5-15 fold
      higher than those measured in the thorax. Chemical speciation of this element in
      tissues of the three polychaete species revealed a major contribution of
      methylated arsenic compounds, like dimethylarsinate (DMA) and, to a lower extent,
      monomethylarsonate (MMA) and trimethylarsine oxide (TMAO). Although the
      biotransformation of inorganic arsenic might represent a detoxification mechanism
      in polychaetes from hydrothermal vents, the elevated levels of methylated forms
      of arsenic in branchial tissues also suggest an ecological role of this element
      as an antipredatory strategy for more vulnerable tissues toward generalist
      consumers.

PMID- 29037571
TI  - Effect of Ruta chalepensis on Zinc, Lipid Profile and Antioxidant Levels in the
      Blood and Tissue of Streptozotocin-Induced Diabetes in Rats Fed Zinc-Deficient
      Diets.
AB  - OBJECTIVES: In diabetes, oxidative stress and lipid abnormalities are common and
      pronounced and represent important factors that are involved in the development
      of complications of diabetes. Zinc deficiency generally induces oxidative stress,
      but it is well known that the antioxidant Ruta chalepensis has an effective
      modulator role in oxidative stress in metabolic diseases. The aim of this study
      was to investigate the effect of R. chalepensis extract on blood biochemical
      parameters, tissue zinc status and antioxidant systems in rats with diabetes that
      were fed zinc-deficient diets. METHODS: We divided 28 male albino Wistar rats
      into 4 groups: 2 groups (1 group with diabetes, 1 group without diabetes) were
      fed zinc-sufficient diets, while the other 2 groups of rats with diabetes were
      fed zinc-deficient diets. One group was not treated, and the other was treated
      with the extract of R. chalepensis. After 3 weeks of dietary manipulation, the
      fasting animals were killed. RESULTS: The body-weight gains of the zinc-deficient
      animals with diabetes were lower than those of the zinc-adequate animals with
      diabetes. It was noticed also that inadequate dietary zinc intake increased the
      glucose, cholesterol, triglyceride, urea, uric acid, creatinine and lipid
      peroxidation levels. In addition, the zinc-deficient diet led to a decrease in
      zinc tissues (femur, liver, kidney), glutathione concentration and both
      glutathione peroxidase and glutathione-S-transferase activities. However, R.
      chalepensis treatment ameliorated all the previous parameters approximately to
      their normal levels. CONCLUSIONS: It seems that R. chalepensis supplementation is
      a potent factor in reducing the oxidative severity of zinc deficiency in
      experimental diabetes through its hypoglycemic and antioxidant actions.

PMID- 29037572
TI  - Gender-Related Differences in the Control of Cardiovascular Risk Factors in
      Primary Care for Elderly Patients With Type 2 Diabetes: A Cohort Study.
AB  - OBJECTIVE: The aim of this study was to estimate the association between gender
      and control of diabetes and other cardiovascular risk factors in elderly patients
      with type 2 diabetes mellitus. METHODS: The sujets ages cohort is an
      observational study whose main objective was to describe the real-life management
      of elderly patients with type 2 diabetes mellitus in France. Nine hundred eighty
      three patients with diabetes (517 men and 466 women) were recruited by 213
      general practitioners and were followed up prospectively every 6 months for 3
      years. Diabetes, hypertension and dyslipidemia were considered controlled if the
      glycated hemoglobin (A1C) was <=7%, blood pressure was <140/90 mm Hg and low
      density lipoprotein (LDL) cholesterol was <=100 mg/dL. A1C levels and blood
      pressure measurements were recorded every 6 months for all patients. LDL
      cholesterol levels were optionally sampled every year. RESULTS: Women were older
      than men (77.3+/-5.72 vs. 76.1+/-6.01 years), more likely to be alone, less
      likely to be smokers/ex-smokers and less likely to have cardiovascular disease at
      baseline. Mean A1C levels of female patients (6.98%+/-1.03%) did not differ from
      those of male patients (6.91%+/-0.96%). Mean blood pressure measurements during
      follow up were not different between male and female patients. In contrast,
      female patients had significantly higher LDL cholesterol levels than male
      counterparts (105.2+/-32.6 vs. 94.9+/-29.1 mg/dL), regardless of statin therapy.
      CONCLUSION: Our results suggest no difference in the management of cardiovascular
      risk factors between elderly female patients with type 2 diabetes mellitus and
      their male counterparts, except for LDL cholesterol, which is significantly
      higher in women.

PMID- 29037573
TI  - Pharmacists' Scope of Practice: Supports for Canadians with Diabetes.
AB  - OBJECTIVES: The pharmacists' role in Canada has significantly advanced over the
      past decade, resulting in increasing access to primary care services. This study
      aimed to characterize pharmacists' expanded scope of practice as it relates to
      providing services to Canadians with diabetes. METHODS: This environmental scan
      characterized services that could be useful to Canadians with diabetes in each of
      the provinces (excluding the territories): immunizations, medication prescribing,
      ordering and interpreting laboratory tests, and medication reviews. Researchers
      also collected information on pharmacists' access to health information. Data
      were collected from regulatory authorities in each province, from pharmacy
      stakeholders and through a web search. RESULTS: Pharmacists' scope of practice
      varies widely across the Canadian provinces. Three provinces have medication
      review programs focused specifically on diabetes, and many people with diabetes
      can access publicly funded medication reviews. Other than in Quebec, pharmacists
      can provide influenza (publicly funded) and pneumococcal vaccinations (publicly
      funded in British Columbia, Alberta and Manitoba). All pharmacists in Canadian
      provinces can renew prescriptions to ensure continuity of therapy. Pharmacists
      have varying levels of other prescriptive authority. Pharmacists in all provinces
      (except Ontario) can access provincial prescription information; in 4 provinces,
      they can access laboratory results, and in 3 provinces, they can order and
      interpret laboratory results, such as glycated hemoglobin levels. CONCLUSIONS:
      Canadians with diabetes can expect to receive influenza vaccines and have
      medications renewed at their pharmacies. Many patients with diabetes qualify for
      a publicly funded medication review, and some provinces allow pharmacists to
      order and interpret laboratory results. This expanded scope provides greater
      opportunities for pharmacists to help support patients with diabetes in
      conjunction with other health-care team members.

PMID- 29037574
TI  - County-level assessment of United States kindergarten vaccination rates for
      measles mumps rubella (MMR) for the 2014-2015 school year.
AB  - United States kindergarten measles-mumps-rubella (MMR) vaccination rates are
      typically reported at the state level by the Centers for Disease Control and
      Prevention (CDC). The lack of local MMR data prevents identification of areas
      with low vaccination rates that would be vulnerable to the spread of disease. We
      collected county-level vaccination rates for the 2014-2015 school year with the
      objective of identifying these regions. We requested county-level kindergarten
      vaccination data from state health departments, and mapped these data to
      visualize geographic patterns in achievement of the 95% MMR vaccination target.
      We aggregated the county-level data to the state level for comparison against CDC
      state estimates. We also analyzed the relationship of MMR vaccination level with
      county-level and state-level poverty (using U.S. census data), using both a
      national mixed model with state as a random effect, and individual linear
      regression models by state. We received county vaccination data from 43 states.
      The median kindergarten MMR vaccination rate was 96.0% (IQR 89-98) across all
      counties, however, we estimated that 48.4% of the represented counties had
      vaccination rates below 95%. Our state estimates closely reflected CDC values.
      Nationally, every 10% increase in under-18 county poverty was associated with a
      0.24% increase in MMR vaccination rates (95% CI: -0.07%; 0.54%), but the
      direction of this relationship varied by state. We found that county data can
      reveal vaccination trends that are unobservable from state-level data, but we
      also discovered that the current availability of county-level data is inadequate.
      Our findings can be used by state health departments to identify target areas for
      vaccination programs.

PMID- 29037575
TI  - Using best-worst scaling to rank factors affecting vaccination demand in northern
      Nigeria.
AB  - BACKGROUND: Understanding and ranking the reasons for low vaccination uptake
      among parents in northern Nigeria is critical to implement effective policies to
      save lives and prevent illnesses. This study applies best-worst scaling (BWS) to
      rank various factors affecting parents' demand for routine childhood
      immunization. METHODS: We conducted a household survey in Nahuche, Zamfara State
      in northern Nigeria. Nearly two hundred parents with children under age five were
      asked about their views on 16 factors using a BWS technique. These factors
      focused on known attributes that influence the demand for childhood immunization,
      which were identified from a literature review and reviewed by a local advisory
      board. The survey systematically presented parents with subsets of six factors
      and asked them to choose which they think are the most and least important in
      decisions to vaccinate children. We used a sequential best-worst analysis with
      conditional logistic regression to rank factors. RESULTS: The perception that
      vaccinating a child makes one a good parent was the most important motivation for
      parents in northern Nigeria to vaccinate children. Statements related to trust
      and social norms were ranked higher in importance compared to those that
      highlighted perceived benefits and risks, healthcare service, vaccine
      information, or opportunity costs. Fathers ranked trust in the media and views of
      their leaders to be of greatest importance, whereas mothers placed greater
      importance on social perceptions and norms. Parents of children without routine
      immunization ranked their trust in local leaders about vaccines higher in
      considerations, and the media's views lower, compared to parents with children
      who received routine immunization. CONCLUSIONS: Framing immunization messages in
      the context of good parenting and hearing these messages from trusted information
      sources may motivate parental uptake of childhood vaccines. These results are
      useful to policymakers to prioritize resources in order to increase awareness and
      demand for childhood immunization.

PMID- 29037577
TI  - Validation of administrative data to estimate vaccine impact: Audit of the Fiji
      hospital admissions electronic database, 2007-2011 & 2014-2015.
AB  - OBJECTIVES: Post-licensure studies to evaluate vaccine impact are an important
      component of introducing new vaccines. Such studies often rely on routinely
      collected data but the limitations to these data must be understood. To validate
      administrative data for use in 10-valent pneumococcal conjugate and rotavirus
      vaccine impact evaluations we have audited the two electronic database capturing
      hospital admissions in Fiji for completeness and consistency. METHODS: Hospital
      admission data for one week per year between 2007-2011 and 2014-2015 was
      collected from ward registers for selected hospitals. Ward registers were defined
      as the reference standard and compared to data captured in electronic databases.
      Data quality was assessed for completeness of admissions data (percentage of
      admissions in the electronic database, expressed as sensitivity), consistency of
      complete reporting (determined by identifying variables associated to complete
      reporting), and completeness of coding (percentage of admissions in the
      electronic database with an assigned ICD-10-AM code). RESULTS: Over all hospitals
      and years, the sensitivity for completeness of admission data was 83% (95% CI:
      81.3, 84.6). Consistency of complete reporting varied and was highest at tertiary
      hospitals using the electronic database (sensitivity: 89.1%, 95% CI: 87.4, 90.7).
      The overall completeness of coding at tertiary hospitals was 90.8% (95% CI: 90.5,
      91.1) with annual and hospital variation. CONCLUSION: The administrative data in
      the electronic databases in Fiji are of reasonable quality for the vaccine impact
      evaluation. This quantification of the missing data can be used to adjust the
      vaccine impact estimates.

PMID- 29037576
TI  - Pertussis seroepidemiology in women and their infants in Sarlahi District, Nepal.
AB  - BACKGROUND: Infants are at greatest risk for pertussis morbidity and mortality.
      Maternal vaccination during pregnancy has been shown to prevent pertussis in
      young infants in high- and middle-income countries. However, data on the levels
      of maternal pertussis antibodies and the efficiency of transplacental transfer in
      low-income South Asian settings are limited. OBJECTIVE: To estimate the
      prevalence of maternal pertussis antibodies and the efficiency of transplacental
      transfer in rural southern Nepal. DESIGN/METHODS: Paired maternal-infant blood
      samples were collected from a subsample of participants in a randomized,
      controlled trial of maternal influenza immunization (n=291 pairs). Sera were
      tested by enzyme-linked immunosorbent assays for pertussis toxin, filamentous
      hemagglutinin, pertactin, and fimbriae. Maternal and infant pertussis antibody
      levels and transplacental transfer efficiency were determined and potential
      factors associated with both were assessed. RESULTS: Elevated maternal antibodies
      to pertussis toxin, suggesting recent pertussis infection, were rarely detected
      (4%, tested n=305). However, paired maternal-cord sera were highly correlated
      across all antibodies; transplacental antibody transfer ratios for pertussis
      toxin were 1.14 (n=291, 95% CI 1.07-1.20); filamentous hemagglutinin 1.10 (n=120,
      95% CI: 1.01-1.20); fimbriae 2/3 1.05 (n=120, 95% CI: 0.96-1.15) and pertactin
      0.96 (n=289, 95% CI: 0.91-1.00). Older gestational age was associated with
      increased pertussis toxin and decreased fimbriae 2/3 antibody transport.
      CONCLUSIONS: A low prevalence of maternal antibody to all four pertussis antigens
      was noted in Nepal, but transplacental antibody transfer was efficient. No
      consistent demographic factors were associated with elevated maternal antibody
      levels or efficiency of transplacental transfer. If an increase in infant
      pertussis disease burden was detected in this population, maternal immunization
      could be an effective intervention to prevent disease in early infancy.

PMID- 29037579
TI  - Rotarix(r) and RotaTeq(r) administration to preterm infants in the neonatal
      intensive care unit: Review of available evidence.
AB  - Rotavirus (RV) is the leading cause of severe acute gastroenteritis (GE) in
      infants worldwide. Several vaccines against RV were developed to reduce disease
      burden, hospitalization rates and health utilization costs. RV GE is a serious
      disease in preterm (PT) infants, and the administration of RV vaccine to these at
      risk subjects at the proper time could have great clinical relevance. However,
      most data on the efficacy and safety of RV vaccinations were collected in healthy
      full-term infants, and few studies investigated PT infants. The lack of studies
      in PT infants may explain why neonatologists in several neonatal intensive care
      units (NICUs) do not follow the official recommendations, which indicate that RV
      vaccine may be administered in hospitals. Increasing neonatologists' knowledge on
      the efficacy and safety of RV vaccines and defining PT candidates for vaccination
      and the necessary precautions are extremely important to avoid potential vaccine
      virus transmission and improve RV vaccination coverage in PT infants. Further
      studies should analyse the impact of vaccination of PT infants of different
      gestational ages and various clinical histories in stable conditions in the NICU
      with a careful monitoring of adverse events to the vaccine and RV GE occurrence.
      Only data that confirm the efficacy and safety of RV vaccines in large numbers of
      PT infants with different characteristics will convince neonatologists to use RV
      vaccines in PT infants hospitalized in NICUs.

PMID- 29037578
TI  - A phase I safety and immunogenicity dose escalation trial of plague vaccine,
      Flagellin/F1/V, in healthy adult volunteers (DMID 08-0066).
AB  - INTRODUCTION: Intentional aerosolization of Yersinia pestis may result in
      pneumonic plague which is highly fatal if not treated early. METHODS: We
      conducted a phase 1 randomized, double blind (within each group), placebo
      controlled, dose escalation trial to evaluate a plague vaccine, Flagellin/F1/V,
      in healthy adults aged 8 through 45years. Vaccine was administered
      intramuscularly on Days 0 and 28 at a dose of 1, 3, 6 or 10mcg. Subjects were
      observed for 4h after vaccination for cytokine release syndrome. Reactogenicity
      and adverse events (AE) were collected for 14 and 28days, respectively, after
      each vaccination. Serious AE were collected for the entire study. ELISA antibody
      and cytokines were measured at multiple time points. Subject's participation
      lasted 13months. RESULTS: Sixty healthy subjects were enrolled; 52% males, 100%
      non-Hispanic, 91.7% white and mean age 30.8years. No severe reactogenicity events
      occurred; most AE were mild. No serious AE related to vaccine occurred. A dose
      response effect was observed to F1, V and flagellin. The peak ELISA IgG antibody
      titers (95% CI) after two 10mcg doses of vaccine were 260.0 (102.6-659.0) and
      983.6 (317.3-3048.8), respectively, against F1 and V antigens. The 6mcg dose
      group provided similar titers. Titers were low for the placebo, 1mcg and 3mcg
      recipients. A positive antibody dose response was observed to F1, V and
      flagellin. Vaccine antigen specific serum IgE was not detected. There were no
      significant rises in serum or cellular cytokine responses and no significant IgG
      increase to flagellin after the second dose. CONCLUSION: The Flagellin/F1/V
      vaccine exhibited a dose dependent increase in immunogenicity and was well
      tolerated at all doses. Antibody specific responses to F1, V and flagellin
      increased as dose increased. Given the results from this trial, testing higher
      doses of the vaccine may be merited.

PMID- 29037580
TI  - A cross sectional survey to evaluate knowledge, attitudes and practices regarding
      seasonal influenza and influenza vaccination among diabetics in Pretoria, South
      Africa.
AB  - BACKGROUND: In South Africa, influenza vaccination is recommended to all
      diabetics. However, vaccination coverage among diabetics remains low. Therefore,
      this study aimed to explore the knowledge, attitudes, and practices among people
      with diabetes in Pretoria regarding seasonal influenza and influenza vaccination.
      METHOD: A cross-sectional survey was conducted among type 1 and 2 diabetes
      mellitus patients who attended diabetic clinics in two major tertiary hospitals
      in Pretoria, South Africa from October to December 2015. The pilot-tested
      questionnaire consists of 32 quantitative questions that covered seasonal
      influenza and influenza vaccination in terms of the patient's demographics,
      medical history and knowledge, attitudes and practices. RESULTS: A total of 292
      completed questionnaires were received with a response rate of 70.0%. Of these,
      162 participants (55.5%) believed that influenza is the same as common cold.
      While 96 (32.9%) participants were aware that they were at higher risk of
      complications of influenza, only 86 (29.5%) participants considered vaccination
      as an effective means in preventing serious influenza-related complication. Even
      though 167 (57.2%) participants had heard of the vaccine to prevent influenza,
      only 84 (28.8%) participants were previously vaccinated. Multivariate analysis
      shows that participants with good attitude score for influenza vaccination were
      18.4 times more likely to be vaccinated compared with those with poor attitude
      score (OR =18.4, 95%CI. 5.28-64.10, p = .001). Among those previously vaccinated,
      advice from their doctors (82/84, 97.6%) was the main factor encouraging
      vaccination. Top reasons given by participants who had never been vaccinated
      before (208/292, 71.2%) include use of alternative protection (107/208, 51.4%)
      and that vaccination is not necessary because flu is just a minor illness
      (93/208, 44.7%). CONCLUSION: Uptake of seasonal vaccination among diabetics in
      Pretoria is low. Level of knowledge and perception are the main barriers to
      vaccination. Health care provider's advice may be an important key predictor of
      previous influenza vaccination and they should continue to educate and encourage
      all diabetics to get vaccinated for influenza at least once yearly.

PMID- 29037581
TI  - Pulmonary embolism due to exogenous estrogen intoxication.
AB  - OBJECTIVE: Pulmonary embolism is a relatively common clinical presentation of
      venous thromboembolism, which develops in relation to acute pulmonary arterial
      occlusion mostly caused by thrombi of the lower limbs. CASE REPORT: 29year old
      female admitted to emergency department with pulmonary thromboembolism due to an
      ingestion of 17 Diana 35 pills (2 mg cyproterone acetate and 0.035mg ethinyl
      estradiol) in a suicide attempt without any previously known predisposing
      factors. After thrombolytic therapy, the patient was discharged with oral
      warfarin treatment. DISCUSSION: We know that exogenous estrogen increase the risk
      of venous thromboembolism in therapeutic use. It should be kept in mind that even
      single ingestion of a single high-dose exogenous estrogen intake may induce
      pulmonary thromboembolism.

PMID- 29037582
TI  - Endoscopic versus microscopic approach in attic cholesteatoma surgery.
AB  - PURPOSE: Compare the outcomes of primary exclusive endoscopic ear surgery with
      those of the microscopic ear surgery in a group of patients affected by attic
      cholesteatoma. MATERIALS AND METHODS: Eighty patients suffered from attic
      cholesteatoma. Forty patients surgical treated with endoscopic ear surgery and
      forty patients surgical treated with microscopic ear surgery. RESULTS: No
      statistical differences were found in the parameters analysed (frequency of
      facial nerve dehiscence, age, disease duration, site of dehiscence) between the
      endoscopic and microscopic groups indicating a homogeneous selection thus
      providing a good comparison of the outcomes between the two groups. None of the
      patients in our survey developed postoperative iatrogenic facial palsy. Graft
      success rate was 100% in both groups. The overall operation time of endoscopic
      ear surgery presented a mean value of 87.8min, while in the group of patients
      treated via microscopic ear surgery a lower mean value of 69.9min was reported.
      The average healing time was 36.3days for the endoscopic subgroup and 47.8days
      for the microscopic subgroup. CONCLUSION: The surgical outcomes of endoscopic ear
      surgery are comparable to those of the conventional approach in terms
      postoperative air-conduction, graft success rate and taste sensation. The
      analysis of postoperative pain and healing times showed better results for EES.
      The mean operative times of endoscopic ear surgery gradually shortened as the
      surgeons gained expertise in performing one-hand surgery.

PMID- 29037583
TI  - Landmarks for the preservation of the middle temporal artery during mastoid
      surgery: Cadaveric dissection study.
AB  - IMPORTANCE: The middle temporal artery flap is a vascularized periosteal flap
      that is highly useful for otologic reconstruction including the middle cranial
      fossa, mastoidectomy defect, and external auditory canal. The course of the
      artery is close to the external auditory canal and is easily injured during
      preliminary exposure and elevation of flaps. OBJECTIVES: To describe the course
      of the middle temporal artery in relation to the external auditory canal and the
      superficial temporal artery in order to enhance preservation and use in otologic
      reconstruction. DESIGN: Dissection of preserved, injected cadaveric temporal
      bones. SETTING: Anatomical laboratory. PARTICIPANTS: Seven cadaveric temporal
      bones. INTERVENTION: Temporal bones were dissected in a planar manner to identify
      the middle temporal artery along the squamous temporal bone to its origin. The
      superior border of the external auditory canal was divided, horizontally, into
      thirds to create three measurement points. Distances between the middle temporal
      artery and the bony portion of the external auditory canal were then determined.
      MAIN OUTCOMES AND MEASURES: Horizontal diameter of the external auditory canal,
      distance from the superior-most border of the external auditory canal to the
      middle temporal artery, various patterns of the middle temporal artery. RESULTS:
      The middle temporal artery branched from the superficial temporal artery in all
      specimens. Mean horizontal diameter of the external auditory canal was 9.97mm.
      Mean distances between the bony portion of the external auditory canal and middle
      temporal artery for the first, second, and third points along the horizontal
      diameter of the external auditory canal were 1.57, 2.96, and 4.02mm,
      respectively. In at least one specimen, the artery dipped into the external
      auditory canal. CONCLUSIONS AND RELEVANCE: The middle temporal artery runs
      closest to the external auditory canal at the anterosuperior border. To preserve
      the middle temporal artery for use in reconstruction after otologic surgery, the
      surgeon should avoid dissection superior to the external auditory canal until the
      artery is positively identified.

PMID- 29037584
TI  - Fungal biotransformation of diuretic and antihypertensive drug spironolactone
      with Gibberella fujikuroi, Curvularia lunata, Fusarium lini, and Aspergillus
      alliaceus.
AB  - Derivatives of spironolactone (1), a diuretic and antihypertensive drug, were
      synthesized by using fungal cells for the first time. Ten different fungi were
      screened for their ability to biotransform 1, four of which were able to produce
      metabolites 2-8. Gibberella fujikuroi produced canrenone (2), 1-dehydrocanrenone
      (3), Curvularia lunuta provided compound 2, and 7alpha-thio-spironolactone (4),
      Fusarium lini yielded compounds 2, 3, 1beta-hydroxycanrenone (5), 1alpha
      hydroxycanrenone (6), 1-dehydro-15alpha-hydroxycanrenone (7), and 15alpha
      hydroxycanrenone (8), while Aspergillus alliaceus was able to produce all the
      seven metabolites. Metabolites 5, 6, and 7 were identified as new compounds.
      Their structures were elucidated by using different spectroscopic techniques.
      Substrate 1 and its metabolites 2, 3, and 5-8 were also evaluated for alpha
      glucosidase inhibitory activity in vitro. Substrate 1 was found to be strongly
      active with IC50 = 335 +/- 4.3 MUM as compared to the standard drug acarbose IC50
      = 840 +/- 1.73 MUM, whereas all of resulting metabolites were found to be
      inactive.

PMID- 29037585
TI  - Iatrogenic mandibular fracture after open reduction and internal fixation in a
      patient with osteogenesis imperfecta.
AB  - To the best of our knowledge, this is the first report to discuss the possible
      mechanisms of an iatrogenic fracture during operation on an original mandibular
      fracture in a patient with osteogenesis imperfecta.

PMID- 29037586
TI  - Successive and discrete spaced conditioning in active avoidance learning in young
      and aged zebrafish.
AB  - We designed an automated device to study active avoidance learning abilities of
      zebrafish. Open source tools were used for the device control, statistical
      computing, and graphic outputs of data. Using the system, we developed active
      avoidance tests to examine the effects of trial spacing and aging on learning.
      Seven-month-old fish showed stronger avoidance behavior as measured by color
      preference index with discrete spaced training as compared to successive spaced
      training. Fifteen-month-old fish showed a similar trend, but with reduced
      cognitive abilities compared with 7-month-old fish. Further, in 7-month-old fish,
      an increase in learning ability during trials was observed with discrete, but not
      successive, spaced training. In contrast, 15-month-old fish did not show increase
      in learning ability during trials. Therefore, these data suggest that discrete
      spacing is more effective for learning than successive spacing, with the
      zebrafish active avoidance paradigm, and that the time course analysis of active
      avoidance using discrete spaced training is useful to detect age-related learning
      impairment.

PMID- 29037587
TI  - Lipidomic analysis of biological samples: Comparison of liquid chromatography,
      supercritical fluid chromatography and direct infusion mass spectrometry methods.
AB  - Lipidomic analysis of biological samples in a clinical research represents
      challenging task for analytical methods given by the large number of samples and
      their extreme complexity. In this work, we compare direct infusion (DI) and
      chromatography - mass spectrometry (MS) lipidomic approaches represented by three
      analytical methods in terms of comprehensiveness, sample throughput, and
      validation results for the lipidomic analysis of biological samples represented
      by tumor tissue, surrounding normal tissue, plasma, and erythrocytes of kidney
      cancer patients. Methods are compared in one laboratory using the identical
      analytical protocol to ensure comparable conditions. Ultrahigh-performance liquid
      chromatography/MS (UHPLC/MS) method in hydrophilic interaction liquid
      chromatography mode and DI-MS method are used for this comparison as the most
      widely used methods for the lipidomic analysis together with ultrahigh
      performance supercritical fluid chromatography/MS (UHPSFC/MS) method showing
      promising results in metabolomics analyses. The nontargeted analysis of pooled
      samples is performed using all tested methods and 610 lipid species within 23
      lipid classes are identified. DI method provides the most comprehensive results
      due to identification of some polar lipid classes, which are not identified by
      UHPLC and UHPSFC methods. On the other hand, UHPSFC method provides an excellent
      sensitivity for less polar lipid classes and the highest sample throughput within
      10min method time. The sample consumption of DI method is 125 times higher than
      for other methods, while only 40MUL of organic solvent is used for one sample
      analysis compared to 3.5mL and 4.9mL in case of UHPLC and UHPSFC methods,
      respectively. Methods are validated for the quantitative lipidomic analysis of
      plasma samples with one internal standard for each lipid class. Results show
      applicability of all tested methods for the lipidomic analysis of biological
      samples depending on the analysis requirements.

PMID- 29037588
TI  - Magnetic covalent triazine framework for rapid extraction of phthalate esters in
      plastic packaging materials followed by gas chromatography-flame ionization
      detection.
AB  - Covalent triazine frameworks (CTFs), featuring with high surface area, good
      thermal, chemical and mechanical stability, are good adsorbents in sample
      pretreatment. Herein, magnetic CTFs/Ni composite was prepared by in situ
      reduction of nickel ions on CTFs matrix with a solvothermal method. The prepared
      CTFs/Ni composite exhibited good preparation reproducibility, high chemical
      stability, and high extraction efficiency for targeted phthalate esters (PAEs)
      due to pi-pi interaction and hydrophobic effect. The porous structure of CTFs/Ni
      composite benefited the fast transfer of target PAEs from aqueous solution to the
      adsorbents, and the integrated magnetism contributed to the rapid separation of
      adsorbents from sample and elution solution. Based on it, a novel method of
      magnetic solid phase extraction (MSPE) combined with gas chromatography-flame
      ionization detector (GC-FID) was developed for the analysis of PAEs including
      dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP),
      benzyl butyl phthalate (BBP), di-2-ethylhexl phthalate (DEHP), and di-n-octyl
      phthalate (DNOP) in plastic packaging materials. Under the optimal experimental
      conditions, the limits of detection (LODs, S/N=3) for six PAEs were found to be
      in the range of 0.024-0.085mg/kg. The linear range was 0.32-16mg/kg for DMP, DEP,
      0.08-80mg/kg for DBP, 0.16-32mg/kg for BBP, DEHP, and 0.32-32mg/kg for DNOP,
      respectively. The enrichment factors ranged from 59 to 88-fold (theoretical
      enrichment factor was 133-fold). The proposed method was successfully applied to
      the analysis of PAEs in various plastic packaging materials with recoveries in
      the range of 70.6-119% for the spiked samples. This method is characterized with
      short operation time, high sensitivity, low consumption of harmful organic
      solvents and can be extended to the analysis of other trace aromatic compounds.

PMID- 29037589
TI  - A twin purification/enrichment procedure based on two versatile solid/liquid
      extracting agents for efficient uptake of ultra-trace levels of lorazepam and
      clonazepam from complex bio-matrices.
AB  - In this research work, two consecutive dispersive solid/liquid phase
      microextractions based on efficient extraction media were developed for the
      influential and clean pre-concentration of clonazepam and lorazepam from
      complicated bio-samples. The magnetism nature of the proposed nanoadsorbent
      proceeded the clean-up step conveniently and swiftly (~5min), pursued by a
      further enrichment via a highly effective and rapid emulsification
      microextraction process (~4min) based on a deep eutectic solvent (DES). Finally,
      the instrumental analysis step was practicable via high performance liquid
      chromatography-ultraviolet detection. The solid phase used was an adequate
      magnetic nanocomposite termed as polythiophene-sodium dodecyl benzene
      sulfonate/iron oxide (PTh-DBSNa/Fe3O4), easily and cost-effectively prepared by
      the impressive co-precipitation method followed by the efficient in situ
      sonochemical oxidative polymerization approach. The identification techniques
      viz. FESEM, XRD, and EDX certified the supreme physico-chemical properties of
      this effective nanosorbent. Also the powerful liquid extraction agent, DES, based
      on bio-degradable choline chloride, possessed a high efficiency, tolerable
      safety, low cost, and facile and mild synthesis route. The parameters involved in
      this versatile hyphenated procedure, efficiently evaluated via the central
      composite design (CCD), showed that the best extraction conditions consisted of
      an initial pH value of 7.2, 17mg of the PTh-DBSNa/Fe3O4 nanocomposite, 20 air
      agitation cycles (first step), 245MUL of methanol, 250MUL of DES, 440MUL of THF,
      and 8 air-agitation cycles (second step). Under the optimal conditions, the
      understudied drugs could be accurately determined in the wide linear dynamic
      ranges (LDRs) of 4.0-3000ngmL-1 and 2.0-2000ngmL-1 for clonazepam and lorazepam,
      respectively, with low limits of detection (LODs) ranged from 0.7 to 1.0ngmL-1.
      The enrichment factor (EF) and percentage extraction recovery (%ER) values were
      found to be 75 and 57% for clonazepam and 56 and 42% for lorazepam at the spiked
      level of 75.0ngmL-1, possessing proper repeatabilities (relative standard
      deviation values (RSDs) below 5.9%, n=3). These valid analytical features
      provided quite accurate drug analyses at therapeutically low spans and levels
      below potentially toxic domains, implying a proper purification/enrichment of the
      proposed microextraction procedure.

PMID- 29037590
TI  - Error measures in quantitative structure-retention relationships studies.
AB  - An analysis and comparison of the use of four commonly used error measures (mean
      absolute error, percentage mean absolute error, root mean square error, and
      percentage root mean square error) for evaluating the predictive ability of
      quantitative structure-retention relationships (QSRR) models is reported. These
      error measures are used for reporting errors in the prediction of retention time
      of external test analytes, that is, analytes not employed during model
      development. The error-based validation metrics were compared using a simple
      descriptive statistic, the sum of squared residuals (SSR) of outliers to the edge
      of an error window. The comparisons demonstrate that Percentage Root Mean Squared
      Error of Prediction (RMSEP) provides the best estimate of the predictive ability
      of a QSRR model, having the lowest SSR value of 20.43.

PMID- 29037591
TI  - Compensation of matrix effects in gas chromatography-mass spectrometry analysis
      of pesticides using a combination of matrix matching and multiple isotopically
      labeled internal standards.
AB  - In the multi-residue analysis of pesticides using GC-MS, the quantitative results
      are adversely affected by a phenomenon known as the matrix effect. Although the
      use of matrix-matched standards is considered to be one of the most practical
      solutions to this problem, complete removal of the matrix effect is difficult in
      complex food matrices owing to their inconsistency. As a result, residual matrix
      effects can introduce analytical errors. To compensate for residual matrix
      effects, we have developed a novel method that employs multiple isotopically
      labeled internal standards (ILIS). The matrix effects of ILIS and pesticides were
      evaluated in spiked matrix extracts of various agricultural commodities, and the
      obtained data were subjected to simple statistical analysis. Based on the
      similarities between the patterns of variation in the analytical response, a
      total of 32 isotopically labeled compounds were assigned to 338 pesticides as
      internal standards. It was found that by utilizing multiple ILIS, residual matrix
      effects could be effectively compensated. The developed method exhibited superior
      quantitative performance compared with the common single-internal-standard
      method. The proposed method is more feasible for regulatory purposes than that
      using only predetermined correction factors and is considered to be promising for
      practical applications.

PMID- 29037592
TI  - Adsorption of marine phycotoxin okadaic acid on a covalent organic framework.
AB  - Phycotoxins, compounds produced by some marine microalgal species, can reach high
      concentrations in the sea when a massive proliferation occurs, the so-called
      harmful algal bloom. These compounds are especially dangerous to human health
      when concentrated in the digestive glands of seafood. In order to generate an
      early warning system to alert for approaching toxic outbreaks, it is very
      important to improve monitoring methods of phycotoxins in aquatic ecosystems.
      Solid-phase adsorption toxin tracking devices reported thus far based on
      polymeric resins have not been able to provide an efficient harmful algal bloom
      prediction system due to their low adsorption capabilities. In this work, a water
      stable covalent organic framework (COF) was evaluated as adsorbent for the
      hydrophobic toxin okadaic acid, one of the most relevant marine toxins and the
      parental compound of the most common group of toxins responsible for the
      diarrhetic shellfish poisoning. Adsorption kinetics of okadaic acid onto the COF
      in seawater showed that equilibrium concentration was reached in only 60min, with
      a maximum experimental adsorption of 61mgg-1. Desorption of okadaic acid from the
      COF was successful with both 70% ethanol and acetonitrile as solvent, and the COF
      material could be reused with minor losses in adsorption capacity for three
      cycles. The results demonstrate that COF materials are promising candidates for
      solid-phase adsorption in water monitoring devices.

PMID- 29037593
TI  - Untargeted analysis of chromatographic data for green and fermented rooibos:
      Problem with size effect removal.
AB  - While analyzing chromatographic data, it is necessary to preprocess it properly
      before exploration and/or supervised modeling. To make chromatographic signals
      comparable, it is crucial to remove the scaling effect, caused by differences in
      overall sample concentrations. One of the efficient methods of signal scaling is
      Probabilistic Quotient Normalization (PQN) [1]. However, it can be applied only
      to data for which the majority of features do not vary systematically among the
      studied classes of signals. When studying the influence of the traditional
      "fermentation" (oxidation) process on the concentration of 56 individual peaks
      detected in rooibos plant material, this assumption is not fulfilled. In this
      case, the only possible solution is the analysis of pairwise log-ratios, which
      are not influenced by the scaling constant. To estimate significant features,
      i.e., peaks differentiating the studied classes of samples (green and fermented
      rooibos plant material), we propose the application of rPLR (robust pair-wise log
      ratios) as proposed by Walach et al. [2]. It allows for fast computation and
      identification of the significant features in terms of original variables (peaks)
      which is problematic, while working with the unfolded pair-wise log ratios. As
      demonstrated, it can be applied to designed data sets and in the case of
      contaminated data, it allows proper conclusions.

PMID- 29037595
TI  - Cellular Characterization of OCT and Outer Retinal Bands Using Specific
      Immunohistochemistry Markers and Clinical Implications.
AB  - PURPOSE: OCT has been a technological breakthrough in the diagnosis, treatment,
      and follow-up of many ocular diseases, especially retinal and neuro
      ophthalmologic pathologic conditions. Until now, several controversies have
      arisen over the specific cell types that the bands observed in the OCT represent,
      especially over the 4 outer retinal bands. DESIGN: To correlate the 4 outer
      hyperreflective bands observed in the OCT with the histologic structures using
      human retinal sections and immunocytochemistry at the fovea level. PARTICIPANTS:
      Eyes from human donors. METHODS: Vertical cryosections of human retinas were
      immunostained with antibodies specific for cones photoreceptors, bipolar cells,
      mitochondria, Muller cells, and retinal pigment epithelium (RPE) cells and were
      visualized using confocal microscopy. MAIN OUTCOME MEASURES: Morphological
      correlation between histology and OCT at the fovea level. RESULTS: Triple
      immunolabeling allowed distinguishing between cells types and different cell
      compartments. Immunostaining with guanine nucleotide-binding protein beta 3
      (GNB3) and cellular retinaldehyde-binding protein (CRALBP) antibodies showed all
      retinal layers at the foveola, especially the separation between the outer
      nuclear layer and the Henle fiber layer. CRALBP and cytochrome C (Cyt C)
      immunolabeling revealed that hyperreflective bands 1 and 2, observed in the OCT,
      correspond to the outer limiting membrane and the cone ellipsoids, respectively,
      separated by the cone myoids. CRALBP, cytochrome C, and GNB3 showed that the RPE
      interdigitations extend along the entire external segment of the cones, we do not
      believe them to be the structure responsible for forming the third band. However,
      the identification of small fragments of cone outer segments within the RPE led
      us to characterize the third band as the cone phagosomes located in the top of
      the RPE. Finally, we propose that the fourth band corresponds to the accumulation
      of mitochondria at the basal portion of the RPE, as identified by cytochrome C
      immunoreactivity, and that the hyporeflective band between bands 3 and 4
      corresponds to the RPE nuclei and melanosomes zone. CONCLUSIONS: This study
      proposes a new interpretation of the outer retinal bands that leads to a more
      accurate interpretation of OCT images, providing information about the health of
      cones and their relationship with the RPE, and could help to form a better
      understanding of retinal disease diagnosis and prognosis.

PMID- 29037596
TI  - Attenuated Chemosensory Responsiveness of the Grueneberg Ganglion in Mouse Pups
      at Warm Temperatures.
AB  - Neurons of the Grueneberg ganglion (GG) in the anterior nasal region of mice
      respond to a small set of odorous compounds, including given dimethylpyrazines
      present in mouse urine. Consequently, mouse pups living in murine colonies are
      presumably commonly exposed to such GG-activating substances. Since stimulation
      of the GG elicits alarm and stress reactions in mice, the question arises whether
      such a GG activation potentially inducing stress could be reduced when pups might
      rather feel secure in the presence of their mother. Being together with their
      warmth-giving dam, mouse pups experience a nest temperature of ~35  degrees C.
      Therefore, we hypothesized that such a warm temperature may attenuate the
      responses of GG neurons to dimethylpyrazines. Monitoring the expression of the
      activity marker c-Fos, GG responses to dimethylpyrazines were significantly lower
      in pups exposed to these substances at 35  degrees C compared to exposure at 30 
      degrees C. By contrast, dimethylpyrazine-induced responses of neurons in the main
      olfactory epithelium were not diminished at 35  degrees C in comparison to 30 
      degrees C. The attenuated chemosensory responses of GG neurons at 35  degrees C
      coincided with a reduced dimethylpyrazine-evoked activation of the glomeruli in
      the olfactory bulb innervated by GG neurons. The reduction in dimethylpyrazine
      evoked GG responses by warm temperatures was positively correlated with exposure
      time, suggesting that warm temperatures might enhance desensitization processes
      in GG neurons. In summary, the findings indicate that warm temperatures similar
      to those in mouse nests in the presence of the dam attenuate GG activation by
      colony-derived odorants.

PMID- 29037594
TI  - Epigenetic Modification of MicroRNA-200b Contributes to Diabetic Vasculopathy.
AB  - Hyperglycemia (HG) induces genome-wide cytosine demethylation. Our previous work
      recognized miR-200b as a critical angiomiR, which must be transiently
      downregulated to initiate wound angiogenesis. Under HG, miR-200b downregulation
      is not responsive to injury. Here, we demonstrate that HG may drive vasculopathy
      by epigenetic modification of a miR promoter. In human microvascular endothelial
      cells (HMECs), HG also lowered DNA methyltransferases (DNMT-1 and DNMT-3A) and
      compromised endothelial function as manifested by diminished endothelial nitric
      oxide (eNOS), lowered LDL uptake, impaired Matrigel tube formation, lower NO
      production, and compromised VE-cadherin expression. Bisulfite-sequencing
      documented HG-induced miR-200b promoter hypomethylation in HMECs and diabetic
      wound-site endothelial cells. In HMECs, HG compromised endothelial function.
      Methyl donor S-adenosyl-L-methionine (SAM) corrected miR-200b promoter
      hypomethylaton and rescued endothelial function. In vivo, wound-site
      administration of SAM to diabetic mice improved wound perfusion by limiting the
      pathogenic rise of miR-200b. Quantitative stable isotope labeling by amino acids
      in cell culture (SILAC) proteomics and ingenuity pathway analysis identified HG
      induced proteins and principal clusters in HMECs sensitive to the genetic
      inhibition of miR-200b. This work presents the first evidence of the miR-200b
      promoter methylation as a critical determinant of diabetic wound angiogenesis.

PMID- 29037597
TI  - Tuning of Neuronal Interactions in the Lateral Ventral Tegmental Area by Dopamine
      Sensitivity.
AB  - The Ventral Tegmental Area (VTA) contains a considerable population of
      rhythmically firing dopaminergic neurons, which are influenced by auto-inhibition
      due to extra-synaptic dopamine release resulting in volume transmission. Using a
      Multi-Electrode-Array we simultaneously recorded in vitro from multiple VTA
      dopamine neurons in the rat and studied their mutual interactions. We observed
      that the dopamine sensitivity (EC50) of the neurons (i.e. the relation between
      dopamine concentration and firing rate) was quite variable within the recorded
      population. The interactions between pairs of neurons were quantified using the
      Granger causality. We found that the dopamine sensitivity determined the role of
      a neuron in the local VTA population. Highly sensitive neurons became followers
      (of the population rhythm), whereas less sensitive dopamine neurons played a more
      leading role. This was confirmed by the application of sulpiride which reduces
      the dopamine sensitivity of all neurons through competition and abolishes the
      structure in the interactions. These findings imply that therapeutics, which have
      an easy to understand effect on firing rate, could have a more complicated effect
      on the functional organization of the local VTA population, through volume
      transmission principles.

PMID- 29037598
TI  - Hierarchical Subcortical Sub-Regional Shape Network Analysis in Alzheimer's
      Disease.
AB  - In this paper, by utilizing surface diffeomorphic deformations, we constructed
      and analyzed subcortical shape morphometric networks in 210 healthy control (HC)
      subjects and 175 subjects with Alzheimer's disease (AD), aiming to identify AD
      induced abnormalities in the subcortical shape network. We quantitatively
      analyzed pertinent network attributes of the entire network and each node.
      Further to this, hierarchical analyses were performed; group comparisons were
      conducted at the structure level first and then the sub-region level. The
      bilateral amygdalae, hippocampi, as well as the thalamus were all divided into
      multiple functionally distinct sub-regions. From the structure level analysis, we
      found significant HC-vs-AD group differences in the average local efficiency and
      average global efficiency. In addition, the local nodal efficiencies between the
      right thalamus and all three of the right hippocampus, right amygdala, and left
      thalamus, as well as that between the left amygdala and left hippocampus,
      decreased significantly in AD. According to the sub-regional network analyses, we
      observed significant AD-induced local efficiency decreases between different sub
      regions within the right hippocampus itself and between the subiculum of the
      right hippocampus and the sub-region of the right thalamus connecting to the
      temporal lobe, indicating a degradation of circuit between the hippocampus,
      thalamus, and temporal lobe. Statistical comparisons were performed using 40,000
      non-parametric permutation tests, with false discovery rate correction employed
      for multiple comparison correction.

PMID- 29037599
TI  - Neural Basis of Ventromedial Hypothalamic Oxytocin-Driven Decrease in Appetite.
AB  - OBJECTIVES: Oxytocin (OT) administration in the ventromedial hypothalamic nucleus
      (VMH) reduces chow intake. The nature of VMH OT's anorexigenic action remains
      unclear. Here we provide insight into neural mechanisms underlying VMH OT-driven
      anorexia by (a) identifying feeding-related brain sites activated by VMH OT
      injection; (b) measuring VMH OT receptor (OTr) mRNA changes in response to hunger
      and palatability; and (c) examining how VMH OT affects episodic sweet solution
      intake in sated and hungry rats. METHOD: We established effective doses of VMH OT
      in deprivation-induced and scheduled feeding and determined whether an OT
      antagonist blocks the effect. Then, OT (or antagonist) was injected in the VMH of
      sated rats given episodically sucrose and saccharin solutions. OT was also
      injected in hungry animals offered simultaneously chow and sugar water. Brain
      activation after VMH OT was determined by Fos immunoreactivity (IR). OTr
      expression was established with rtPCR after chow deprivation or saccharin
      exposure. RESULTS: VMH OT decreased intake of chow and the effect was reversed by
      the antagonist, though the antagonist alone was not orexigenic. OT did not affect
      intakes of energy-dilute saccharin and sucrose solutions in sated or hungry rats.
      Fos IR was elevated in the VMH and energy balance-related paraventricular and
      arcuate nuclei, but not reward areas. VMH OTr expression was higher in hungry
      rats than in sated controls; saccharin intake had no effect. CONCLUSION: OT
      acting in the VMH decreases intake driven by energy not by palatability, and it
      stimulates activity of hypothalamic sites controlling energy balance.

PMID- 29037600
TI  - Asymmetric Phosphatidylethanolamine Distribution Controls Fusion Pore Lifetime
      and Probability.
AB  - Little attention has been given to how the asymmetric lipid distribution of the
      plasma membrane might facilitate fusion pore formation during exocytosis.
      Phosphatidylethanolamine (PE), a cone-shaped phospholipid, is predominantly
      located in the inner leaflet of the plasma membrane and has been proposed to
      promote membrane deformation and stabilize fusion pores during exocytotic events.
      To explore this possibility, we modeled exocytosis using plasma membrane SNARE
      containing planar-supported bilayers and purified neuroendocrine dense core
      vesicles (DCVs) as fusion partners, and we examined how different PE
      distributions between the two leaflets of the supported bilayers affected SNARE
      mediated fusion. Using total internal reflection fluorescence microscopy, the
      fusion of single DCVs with the planar-supported bilayer was monitored by
      observing DCV-associated neuropeptide Y tagged with a fluorescent protein. The
      time-dependent line shape of the fluorescent signal enables detection of DCV
      docking, fusion-pore opening, and vesicle collapse into the planar membrane. Four
      different distributions of PE in the planar bilayer mimicking the plasma membrane
      were examined: exclusively in the leaflet facing the DCVs; exclusively in the
      opposite leaflet; equally distributed in both leaflets; and absent from both
      leaflets. With PE in the leaflet facing the DCVs, overall fusion was most
      efficient and the extended fusion pore lifetime (0.7 s) enabled notable detection
      of content release preceding vesicle collapse. All other PE distributions
      decreased fusion efficiency, altered pore lifetime, and reduced content release.
      With PE exclusively in the opposite leaflet, resolution of pore opening and
      content release was lost.

PMID- 29037601
TI  - Implant-oriented navigation in orbital reconstruction. Part 1: technique and
      accuracy study.
AB  - Intraoperative navigation is frequently used to assess the position of the
      implant in orbital reconstruction. Interpretation of the feedback from the
      navigation system to a three-dimensional position of the implant needs to be done
      by the surgeon, and feedback is only gathered after the implant has been
      positioned. An implant-oriented navigation approach is proposed, with real-time
      intuitive feedback during insertion. A technical framework was set up for implant
      oriented navigation, with requirements for planning, implant tracking, and
      feedback. A dedicated navigation instrument was designed and a software tool was
      developed in order to meet the technical requirements. An accuracy study was
      performed to investigate the accuracy of the method in comparison to the regular
      navigation pointer. A proof of concept was provided. The results showed a
      translation error of 1.12-1.15mm for implant-oriented navigation with regular
      registration (pointer 0.71-0.98mm) and 0.81mm with accurate registration (pointer
      0.54mm). Rotational error was found to be small (<3 degrees ). Quantitative and
      intuitive qualitative feedback could be provided to the surgeon in real-time
      during insertion of an orbital implant. Following this proof of concept and
      accuracy study, the implications for the clinical workflow should be evaluated.
      An implant-oriented approach may form the foundation for augmented reality or
      robotic-aided implant insertion.

PMID- 29037602
TI  - HIV/STI Prevention Among Heterosexually Active Black Adolescents With Mental
      Illnesses: Focus Group Findings for Intervention Development.
AB  - Heterosexually active Black adolescents with mental illnesses are at increased
      risk for sexually transmitted infections (STIs), including HIV. However, few
      HIV/STI prevention interventions exist for this demographic. We held seven focus
      groups (N = 33) to elucidate social, cultural, and psychological factors that
      influence HIV/STI risk-related sexual behaviors in this understudied population.
      Seven themes emerged: (a) Blackness and media portrayals, (b) Blackness as a
      source of cultural resilience and pride, (c) psychosocial determinants of condom
      use, (d) consequences of engaging in sexual activity, (e) attitudes and beliefs
      toward sexual behaviors, (f) benefits of sexual activity, and (g) coping
      mechanisms. Participants also supported the feasibility of and interest in
      HIV/STI prevention programs integrated with mental health treatment.
      Transportation, potential breaches of confidentiality, and time were noted
      barriers to participation. Psychoeducational, skills-based programs are needed to
      address the sequelae of mental illnesses as they relate to the sexual decision
      making process in adolescents.

PMID- 29037603
TI  - MRI and CT lung biomarkers: Towards an in vivo understanding of lung
      biomechanics.
AB  - BACKGROUND: The biomechanical properties of the lung are necessarily dependent on
      its structure and function, both of which are complex and change over time and
      space. This makes in vivo evaluation of lung biomechanics and a deep
      understanding of lung biomarkers, very challenging. In patients and animal models
      of lung disease, in vivo evaluations of lung structure and function are typically
      made at the mouth and include spirometry, multiple-breath gas washout tests and
      the forced oscillation technique. These techniques, and the biomarkers they
      provide, incorporate the properties of the whole organ system including the
      parenchyma, large and small airways, mouth, diaphragm and intercostal muscles.
      Unfortunately, these well-established measurements mask regional differences,
      limiting their ability to probe the lung's gross and micro-biomechanical
      properties which vary widely throughout the organ and its subcompartments.
      Pulmonary imaging has the advantage in providing regional, non-invasive
      measurements of healthy and diseased lung, in vivo. Here we summarize well
      established and emerging lung imaging tools and biomarkers and how they may be
      used to generate lung biomechanical measurements. METHODS: We review well
      established and emerging lung anatomical, microstructural and functional imaging
      biomarkers generated using synchrotron x-ray tomographic-microscopy (SRXTM),
      micro-x-ray computed-tomography (micro-CT), clinical CT as well as magnetic
      resonance imaging (MRI). FINDINGS: Pulmonary imaging provides measurements of
      lung structure, function and biomechanics with high spatial and temporal
      resolution. Imaging biomarkers that reflect the biomechanical properties of the
      lung are now being validated to provide a deeper understanding of the lung that
      cannot be achieved using measurements made at the mouth.

PMID- 29037605
TI  - Response Expectancy and the Response to Antidepressant Medication.

PMID- 29037604
TI  - MET Activation and Physical Dynamics of the Metastatic Process: The Paradigm of
      Cancers of Unknown Primary Origin.
AB  - The molecular and cellular mechanisms which drive metastatic spread are the topic
      of constant debate and scientific research due to the potential implications for
      cancer patients' prognosis. In addition to genetics and environmental factors,
      mechanics of single cells and physical interaction with the surrounding
      environment play relevant role in defining invasive phenotype. Reconstructing the
      physical properties of metastatic clones may help to clarify still open issues in
      disease progression as well as to lead to new diagnostic and therapeutic
      approaches. In this perspective cancer of unknown primary origin (CUP) identify
      the ideal model to study physical interactions and forces involved in the
      metastatic process. We have previously demonstrated that MET oncogene is mutated
      with unexpected high frequency in CUPs. We here analyze and discuss how the MET
      activation by somatic mutation may affect physical properties in giving rise to
      such a highly malignant syndrome, as that defined by CUP.

PMID- 29037606
TI  - Plasma HSP90alpha and liver cancer: a potential biomarker?

PMID- 29037608
TI  - Chemokine CCL8 and its receptor CCR5 in the spinal cord are involved in visceral
      pain induced by experimental colitis in mice.
AB  - Visceral hypersensitivity induced by inflammatory bowel disease (IBD) is a
      clinical challenge since the underlying mechanisms remain elusive. Chemokines and
      their receptors have been suggested to modulate inflammatory pain and neuropathic
      pain. However, the exact chemokines involved in visceral pain remain to be
      determined. Here, we investigated the effects of spinal chemokine CCL8 and its
      major receptor CCR5 on the development of visceral hyperalgesia. We showed that
      intracolonic injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice
      produced significant colonic inflammation and visceral hypersensitivity to
      colorectal distension. Moreover, the mRNA and protein expression of CCL8 and CCR5
      in the lumbosacral spinal cord were significantly upregulated. Both of CCL8 and
      CCR5 were expressed in spinal neurons. Furthermore, TNBS induced the activation
      of extracellular signal-regulated kinase (ERK) in the spinal cord. The induction
      of visceral pain by TNBS was attenuated by injection of ERK upstream kinase (MEK)
      inhibitor PD98059. Finally, intrathecal CCL8 neutralizing antibody or CCR5
      antagonist DAPTA dose-dependently suppressed TNBS-evoked visceral hyperalgesia
      and spinal ERK activation. Taken together, these data demonstrated that CCL8 and
      CCR5, expressed and upregulated in spinal neurons after colonic inflammation, are
      involved in the maintenance of visceral hyperalgesia via the activation of spinal
      ERK. Targeting CCL8/CCR5/ERK pathway in the spinal cord might provide a novel
      treatment for the relief of visceral pain.

PMID- 29037607
TI  - Dynamic Organization of lncRNA and Circular RNA Regulators Collectively
      Controlled Cardiac Differentiation in Humans.
AB  - Advances in developmental cardiology have increased our understanding of the
      early aspects of heart differentiation. However, understanding noncoding RNA
      (ncRNA) transcription and regulation during this process remains elusive. Here,
      we constructed transcriptomes for both long noncoding RNAs (lncRNAs) and circular
      RNAs (circRNAs) in four important developmental stages ranging from early
      embryonic to cardiomyocyte based on high-throughput sequencing datasets, which
      indicate the high stage-specific expression patterns of two ncRNA types.
      Additionally, higher similarities of samples within each stage were found,
      highlighting the divergence of samples collected from distinct cardiac
      developmental stages. Next, we developed a method to identify numerous lncRNA and
      circRNA regulators whose expression was significantly stage-specific and shifted
      gradually and continuously during heart differentiation. We inferred that these
      ncRNAs are important for the stages of cardiac differentiation. Moreover,
      transcriptional regulation analysis revealed that the expression of stage
      specific lncRNAs is controlled by known key stage-specific transcription factors
      (TFs). In addition, circRNAs exhibited dynamic expression patterns independent
      from their host genes. Functional enrichment analysis revealed that lncRNAs and
      circRNAs play critical roles in pathways that are activated specifically during
      heart differentiation. We further identified candidate TF-ncRNA-gene network
      modules for each differentiation stage, suggesting the dynamic organization of
      lncRNAs and circRNAs collectively controlled cardiac differentiation, which may
      cause heart-related diseases when defective. Our study provides a foundation for
      understanding the dynamic regulation of ncRNA transcriptomes during heart
      differentiation and identifies the dynamic organization of novel key lncRNAs and
      circRNAs to collectively control cardiac differentiation.

PMID- 29037609
TI  - SCAT3 changes from baseline and associations with X2 Patch measured head
      acceleration in amateur Australian football players.
AB  - OBJECTIVES: To investigate changes from baseline on SCAT3 as a result of football
      game exposure, and association with X2 Patch measured head acceleration events in
      amateur Australian footballers. DESIGN: Prospective cohort. METHODS: Peak linear
      acceleration (PLA) of the head (>10 g) was measured by wearable head acceleration
      sensor X2 Biosystems X-Patch in male (n=34) and female (n=19) Australian
      footballers. SCAT3 was administered at baseline (B) and post-game (PG). RESULTS:
      1394 head acceleration events (HEA) >10 g were measured. Mean and median HEA PLA
      were recorded as 15.2 g (SD=9.2, range=10.0-115.8) and 12.4 g (IQR=11.0-15.6)
      respectively. No significant difference in median HEA PLA (g) was detected across
      gender (p=0.55), however, more HEAs were recorded in males (p=0.03). A greater
      number (p=0.004) and severity (p<0.001) of symptoms were reported PG than at B.
      No significant association between number of HEA or median PLA, and SCAT3 change
      scores (p>0.05 for all), was identified for either gender. CONCLUSIONS: Increase
      in symptom severity post game was not associated with X2 measured HEA. Males
      sustained more HEA, however HEA PLA magnitude did not differ across gender.
      Further work on the validation of head acceleration sensors is required and their
      role in sports concussion research and medical management.

PMID- 29037610
TI  - Coronary Intramural Hematoma Visualized on Multislice CT Angiography.

PMID- 29037611
TI  - Improvement in the Management of Dyslipidemia in a Clinical Practice Population
      at Very High Cardiovascular Risk. The COLIPAR Project.

PMID- 29037612
TI  - Lung Ultrasound for Cardiogenic Shock in VA-ECMO.

PMID- 29037613
TI  - Acute Myocardial Infarction, Stroke and Bilateral Carotid Vasospasm: A Rare
      Association.

PMID- 29037614
TI  - Intra-atrial Right Coronary Artery: An Unknown Disorder.

PMID- 29037615
TI  - Six weeks of Mat Pilates training are enough to improve functional capacity in
      elderly women.
AB  - The aim of the study was to evaluate the effect of Mat Pilates on the functional
      capacity (FC) of elderly women before and after six weeks of intervention.
      Eighteen women aged 62.28 (+/-2.34) participated in the study. Timed Up and Go
      test, Timed Up Stairs, Timed Down Stairs, 30-s Chair Stand, Chair Sit-and-Reach
      and Back Scratch tests were assessed. The results showed significant improvements
      in all FC tests after six weeks of the Mat Pilates intervention. Summarizing,
      only six weeks of Mat Pilates training of 60 min per session, three times a week,
      three series beginning with six repetitions and eight repetitions at the last two
      weeks of intervention, were enough to improve FC in elderly women. Furthermore,
      the exercises difficulty increased from beginners to intermediate.

PMID- 29037616
TI  - The effect of motor control training on kinetics variables of patients with non
      specific low back pain and movement control impairment: Prospective observational
      study.
AB  - INTRODUCTION: The purpose of this study was to determine the effects of motor
      control training on pain, disability and motor control indices in patients with
      nonspecific low back pain (NSLBP) and movement control impairment (MCI) and also
      to evaluate the correlation between the changes in disability and the motor
      control indices. METHODS: Thirty people with NSLBP and MCI based on a clinical
      examination were following either motor control training or normal activity over
      8 weeks. RESULT: Significant differences between pre and post training in the
      experimental group were found in pain, disability and motor control indices.
      There were significant correlations between disability index with vertical ground
      reaction force (r = 0.43) and center of pressure (anterior-posterior) (r = 0.44)
      values. CONCLUSION: The results of this study showed that motor control indices
      are responsive measures to capture change during motor control training directed
      at retraining neuromuscular control, reducing pain and disability.

PMID- 29037617
TI  - The effects of preventive rubber band training on shoulder joint imbalance and
      throwing performance in handball players: A randomized and prospective study.
AB  - OBJECTIVES: To investigate the effects of a strength training program (STP) using
      rubber band exercises. METHODS: Twenty-five athletes were divided into two
      groups: muscular imbalance in the dominant (D) and in the non-dominant (ND) upper
      limbs. Each group was subdivided into experimental and control groups.
      Experimental groups performed eighteen sessions of STP. Athletes were submitted
      to ball throwing and isokinetic strength tests to assess the muscular strength of
      the shoulder rotator muscles and conventional and functional balance ratios.
      RESULTS: STP improved external rotator peak torque (18.0 +/- 0.8 to 21.3 +/- 1.0
      Nm, p < 0.01) and total work (29.3 +/- 0.9 to 34.5 +/- 1.5 J, p < 0.01) in the D
      experimental group, while only total work (34.8 +/- 2.5 to 37.6 +/- 3.1 J, p <
      0.03) improved in the D control group. The ND experimental group also presented
      significant improvement in external rotator peak torque (18.8 +/- 0.8 to 21.1 +/-
      1.3 Nm, p < 0.01) and total work values (29.0 +/- 1.4 to 34.6 to 1.6 J, p < 0.01)
      while there was no strength improvement in the ND control group. The ND
      experimental group showed an improvement in conventional (61.5 +/- 3.5 to 72.7 +/
      3.0%, p = 0.03) and functional (1.0 +/- 0.1 to 1.6 +/- 0.08, p < 0.01) ratios.
      STP did not improve the conventional ratio in the D experimental group. However,
      STP produced a large effect size. The D experimental group presented an
      improvement in ball velocity (49.0 +/- 2.4 to 52.5 +/- 2.2 km/h, p = 0.04) in
      standing position throwing. CONCLUSIONS: STP improves muscular strength of
      external rotator muscles and muscular balance.

PMID- 29037618
TI  - Immediate effect of mental practice with and without mirror therapy on muscle
      activation in hemiparetic stroke patients.
AB  - Mental practice (MP) consists of the repeated mental rehearsal of a physical
      skill without movement, called motor imagery (MI). Studies show that MP and MI
      associated mirror therapy (MPMT) may improve muscle control of the upper limbs in
      hemiparesis. This study aimed to evaluate muscle activation during active flexion
      of the wrist (MA), MP, and MPMT in patients with history of stroke and
      hemiparesis. Individuals diagnosed with stroke showing sequelae of upper limb
      hemiparesis were enrolled. The flexor carpi ulnaris was analyzed using
      electromyography during tasks (MA, MP, MPMT) involving wrist flexion. Greater
      electromyographic activity was detected during MP and MPMT techniques compared to
      active movement (p = 0.02). There was no significant difference between MP and
      MPMT (p = 0.56). These results were found in both the affected limb and
      unaffected limb. Immediate effects on muscle activation are experienced during MP
      and MPMT, and muscle activity was similar with both therapies.

PMID- 29037619
TI  - Evidence based effects of yoga practice on various health related problems of
      elderly people: A review.
AB  - More than 50% of the elderly above 60 years of age suffer from chronic medical
      conditions, the prevalence of which increases with age. Though Yoga has been
      reported as an effective modality in improving various physical and psychological
      aspects of elderly populations, a comprehensive review of Yoga and its effects on
      various health related problems of elderly populations has not yet been reported.
      Hence, we performed PubMed/Medline search to review relevant articles, using
      keyword "yoga and elderly". Relevant articles published since inception till 6th
      October 2016 were included for the review. Based on the available scientific
      literature, this review suggests that the regular practice of Yoga can be
      considered as an effective intervention in improving physical (reduces heart
      rate, blood pressure, blood glucose, oxidative damage, fatigue, weakness, fear of
      fall, and improve heart rate variability, baroreflex sensitivity, insulin
      sensitivity, physical functions, mobility, flexibility, and urinary
      incontinence), mental (reduces depression, anxiety), emotional (reduces anger,
      stress, tension and improve self-efficacy), social (improve life satisfaction),
      and vital (improved vitality) planes of elderly individuals, offering a better
      quality of sleep and quality of life.

PMID- 29037621
TI  - Long term activity participation.

PMID- 29037620
TI  - The effects of strengthening exercises for wrist flexors and extensors on muscle
      strength and counter-stroke performance in amateur table tennis players.
AB  - This study aims to evaluate the effects of strengthening exercises on wrist
      flexor and extensor strength, hand grip strength, and counter-stroke performance.
      Thirty amateur table tennis players were recruited and randomly allocated into
      two groups: the control and the training group (n = 15/group). Pre- and post-data
      were collected. The training group performed home exercises for six weeks using a
      bucket filled with water, while the controls were asked to keep their lifestyle
      as usual. The general characteristics were no significant differences. The
      training group showed significantly higher levels of wrist flexor and extensor
      strength than the control group (p < 0.05). However, the difference in hand grip
      strength was not statistically significant. Both groups showed significant
      improvement in counter-stroke performance (p < 0.05), however, there was no
      difference between the groups. In conclusion, specific strengthening exercises
      increase wrist flexor and extensor strength, but they have no effect on either
      hand grip strength or counter-stroke performance.

PMID- 29037622
TI  - What's in a name: Myofascial Release or Myofascial Induction?

PMID- 29037623
TI  - Osteopathic manipulative treatment for low back and pelvic girdle pain during and
      after pregnancy: A systematic review and meta-analysis.
AB  - BACKGROUND: Low back pain (LBP) is a common complaint during pregnancy. This
      study examined the effectiveness of osteopathic manipulative treatment (OMT) for
      LBP in pregnant or postpartum women. METHODS: Randomized controlled trials
      unrestricted by language were reviewed. Outcomes were pain and functional status.
      Mean difference (MD) or standard mean difference (SMD) and overall effect size
      were calculated. RESULTS: Of 102 studies, 5 examined OMT for LBP in pregnancy and
      3 for postpartum LBP. Moderate-quality evidence suggested OMT had a significant
      medium-sized effect on decreasing pain (MD, -16.65) and increasing functional
      status (SMD, -0.50) in pregnant women with LBP. Low-quality evidence suggested
      OMT had a significant moderate-sized effect on decreasing pain (MD, -38.00) and
      increasing functional status (SMD, -2.12) in postpartum women with LBP.
      CONCLUSIONS: This review suggests OMT produces clinically relevant benefits for
      pregnant or postpartum women with LBP. Further research may change estimates of
      effect, and larger, high-quality randomized controlled trials with robust
      comparison groups are recommended.

PMID- 29037624
TI  - Does leg predomination affect measuring vasti muscle onsets during single leg
      squatting? A reliability study.
AB  - INTRODUCTION: Although measuring vasti muscle onset may reveal whether pain
      relief is associated with altering this parameter during activities in subjects
      with patellofemoral pain syndrome (PFPS), it may be necessary to determine
      whether the inherent properties of the dominant leg influences the reliability of
      measuring VMO-VL muscle onset. The aim of the present study was to examine the
      effect of leg predomination on reliability testing of the VMO-VL muscle onset
      measurement during single leg squatting in healthy subjects. METHODS: The onset
      of VMO and VL muscles of ten healthy subjects with a right dominant leg was
      assessed during single leg squatting. Data was collected from the muscle bellies
      of the VMO and VL. This procedure was performed on the both legs, during three
      separate single leg squats from a neutral position to a depth of approximately 30
      degrees  of knee flexion. Subjects were then asked to repeat the test procedure
      after a minimum of a week's interval. The full wave rectified onsets of VMO and
      VL were then calculated. RESULTS: There was no significant difference between the
      VMO-VL onset mean values of paired test of right and left knees. The ICC (intra
      class correlation coefficient) values during within and between sessions tests
      showed the poor reliability of these measurements on both knees. CONCLUSION: The
      low intratester reliability of within and between sessions measurement of VMO-VL
      onset on the both dominant and non-dominant legs revealed that repeatability of
      these measurements have little accepted reliability, however similar values of
      these measurements indicated that leg predomination does not affect the
      measurements during single leg squatting.

PMID- 29037625
TI  - Effects of proprioceptive neuromuscular facilitation on balance, strength, and
      mobility of an older adult with chronic stroke: A case report.
AB  - This study described the effects of a proprioceptive neuromuscular facilitation
      (PNF) program on balance, strength, and mobility in an older adult with chronic
      stroke. The patient was male, aged 69 years, with right hemiplegia for 17 years,
      and had diminished balance, balance confidence, lower extremity (LE) strength,
      and gait velocity. He received 1 h of PNF-based therapy thrice a week for six
      weeks. Outcome measures were: Mini-BESTest, limits of stability (LOS), Activities
      Specific Balance Confidence Scale (ABC), Five Time Sit-to-Stand Test (FTSST),
      Upright Motor Control Test (UMCT), and 10 Meter Walk Test (10 MWT). The patient
      improved on the Mini-BESTest (25/28, from 21/28), FTSST (27.47 s, from 30.27 s),
      UMCT knee extension (moderate, from weak), and 10 MWT (0.82 m/s, from 0.67 m/s);
      and positive changes in LOS dimensions. PNF was effective in enhancing balance,
      strength, and mobility in an older adult with chronic stroke and may mitigate
      falls risk in this population. More research is needed to determine its impact in
      a larger sample of older people with chronic stroke.

PMID- 29037626
TI  - The acute effects of ankle mobilisations on lower extremity joint kinematics.
AB  - INTRODUCTION: Previous investigations have identified compensatory movement
      strategies (CMS) within the lower extremity or lumbopelvic complex during closed
      chain exercises may be associated with a loss of ankle dorsiflexion range of
      motion (ROM). The aim of this study was to investigate the acute effects of ankle
      mobilisations on proximal joint kinematics during a movement task that demands a
      high amount of ankle dorsiflexion ROM. METHODS: Eight healthy males (mean (SD)
      age 25 (4) years) demonstrating side-to-side asymmetry during the weight-bearing
      lunge test (WBLT) and CMS during the single-leg step-down exercise were accepted
      for this study. Participants completed five repetitions of a single-leg step
      down, both before and after an ankle mobilisation intervention aimed at improving
      joint athrokinematics. A Vicon motion capture system recorded 3D joint and
      segment kinematics of the ankle, knee, hip and pelvis. A paired samples t-test
      was used to identify significant changes of lower extremity joint kinematics
      during the single-leg step-down, before and after mobilisation. RESULTS:
      Following the mobilisation intervention, statistically significant gains in ankle
      dorsiflexion ROM were identified during the WBLT [mean difference 2.425 (0.9377)
      centimeters, t = -7.315, p < 0.01]. No evidence was found of altered joint
      kinematics during the single-leg step-down. CONCLUSION: These findings indicate
      that increases in ankle dorsiflexion ROM do not automatically integrate into
      functional movement tasks.

PMID- 29037627
TI  - Does ultrasound therapy add to the effects of exercise and mobilization in frozen
      shoulder? A pilot randomized double-blind clinical trial.
AB  - OBJECTIVE: This study intended to determine the extent to which Ultrasound could
      add to the effects of exercise and manual therapy in the rehabilitation treatment
      of primary adhesive capsulitis. DESIGN: A pilot double blind randomized clinical
      trial was carried out on 50 patients suffering from primary adhesive capsulitis.
      Intervention included continuous 3 MHz, 1.5 w/cm2 Ultrasound, applied for the
      first group and sham Ultrasound for the second group. In addition specific
      stretching and strengthening exercises as well as glenohumeral joint mobilization
      were delivered to both groups. Pain (VAS), functional ability (using Oxford
      Shoulder Score) and shoulder range of motion were assessed at the baseline, after
      10 sessions of treatment, and at 3 months follow-up. An intention to treat Mixed
      ANOVA analysis was performed to explore the interaction effects of time and group
      on outcome measures. RESULTS: No significant interaction effect of time and group
      was seen on pain, function and Range of Motion (p > 0.05), meaning that the
      amount of improvement in all outcome measures were alike in the two groups.
      CONCLUSION: Applying continuous Ultrasound along with a regimen of semi
      supervised exercise and mobilization in patients with primary adhesive capsulitis
      did not have any additional effect to the placebo Ultrasound, on outcome
      measures. Larger scale studies are needed to confirm the findings.

PMID- 29037628
TI  - Attention-demand effects on respiration in chronic low back pain patients.
AB  - Increasing attention is being drawn towards the involvement of systems other than
      the musculoskeletal one in the presence of low back pain (LBP). Recent evidence
      suggests both cognitive and respiratory functions to be affected in LBP patients.
      The aim of this study was to compare the effect of performance of a cognitive
      task on the respiratory function in LBP patients with that in control
      participants. Capnography and spirometry parameters of 48 participants (24 in
      each group) were assessed under 3 cognitive loading conditions (no, easy and
      difficult cognitive task). The results showed that in both groups the respiratory
      function was significantly affected by the introduction of the cognitive task (p
      < 0.05) and in the same manner (p > 0.05). Capnography and spirometry variables
      alterations were significantly correlated in the no-LBP group (p < 0.05) but
      there was no significant relationship between respiratory parameters and
      capnography and disability indices in the LBP group (p > 0.05). The findings of
      the current study suggest that while performing a cognitive task affects
      respiratory function, the possible differences of LBP patients and control
      participants may not be elicited under simple non-physically demanding postural
      conditions.

PMID- 29037629
TI  - Electromyographic activities of the abdominal muscles during 30% and 75% of
      maximum expiratory pressure.
AB  - The aim of this study was to quantify the activities of the rectus abdominis
      (RA), external oblique (EO), and internal oblique (IO) muscles during 30% and 75%
      of maximum expiratory pressure (PE max). Fifteen healthy male university students
      participated in this study. Electromyographic (EMG) activities of the RA, EO, and
      IO muscles were measured during 30% and 75% of PE max and then normalized
      relative to maximum voluntary contractions (%MVC). All muscles during 75% of PE
      max showed significantly higher %MVC compared to that during 30% of PE max (P <
      0.01). The EO and IO muscles showed significantly higher %MVC compared to the RA
      muscle during 30% and 75% of PE max (P < 0.05). Muscle endurance and strength
      induced by expiratory muscle strength training might be different in each
      abdominal muscle.

PMID- 29037631
TI  - The acute effect of Bowen therapy on pressure pain thresholds and postural sway
      in healthy subjects.
AB  - OBJECTIVE: The purpose of the study is to determine the immediate effect of Bowen
      Therapy in pressure pain threshold and postural sway of healthy individuals.
      DESIGN: Crossover, randomized, and double blinded study. SETTING: University.
      PARTICIPANTS: Participants aged 18 years old or over, naive to Bowen therapy were
      recruited among university students. An a priori sample size calculation
      determined that 34 participants were needed. METHODS: Each participant attended
      two sessions and received Bowen Therapy and a sham procedure. The order in which
      Bowen or the sham procedure were administered was randomized. All participants
      had their postural control and pressure pain thresholds assessed in sessions 1
      and 2 both at baseline and at the end of the session. MAIN OUTCOME MEASUREMENTS:
      Postural control was assessed using a force plate and centre of pressure antero
      posterior and medio-lateral displacement, velocity and total sway area were
      calculated. Pressure pain threshold was measured at 10 different body sites on
      the paraspinal muscles from C1 to S1 using an electronic algometer. RESULT: The
      results showed a significant increase in the anteroposterior displacement (p =
      0.04) and a significantly lower decrease in the mean velocity (p = 0.01) of the
      centre of pressure and a significant increase in the pressure pain thresholds of
      two (out of ten; p <= 0.04) body sites in the group receiving Bowen Therapy
      compared to the group receiving the sham. No other significant differences were
      found. CONCLUSIONS: The findings suggest that Bowen Therapy has inconsistent
      immediate effects on postural control and pain threshold in healthy subjects.
      Further studies are needed using symptomatic participants.

PMID- 29037630
TI  - Hypoalgesic effects of three different manual therapy techniques on cervical
      spine and psychological interaction: A randomized clinical trial.
AB  - OBJECTIVE: The purpose of this study was to evaluate the extent to which
      psychological factors interact with a particular manual therapy (MT) technique to
      induce hypoalgesia in healthy subjects. METHODS: Seventy-five healthy volunteers
      (36 female, 39 males), were recruited in this double-blind, controlled and
      parallel study. Subjects were randomly assigned to receive: High velocity low
      amplitude technique (HVLA), joint mobilization, or Cervical Lateral glide
      mobilization (CLGM). Pressure pain threshold (PPT) over C7 unilaterally,
      trapezius muscle and lateral epicondyle bilaterally, were measured prior to
      single technique MT was applied and immediately after to applied MT. Pain
      catastrophizing, depression, anxiety and kinesiophobia were evaluated before
      treatment. RESULTS: The results indicate that hypoalgesia was observed in all
      groups after treatment in the neck and elbow region (P < 0.05), but mobilization
      induces more hypoalgesic effects. Catastrophizing interacted with change over
      time in PPT, for changes in C7 and in manipulation group. CONCLUSIONS: All the MT
      techniques studied produced local and segmental hypoalgesic effects, supporting
      the results of previous studies studying the individual interventions.
      Interaction between catastrophizing and HVLA technique suggest that whether
      catastrophizing level is low or medium, the chance of success is high, but high
      levels of catastrophizing may result in poor outcome after HVLA intervention.
      TRIAL REGISTRATION: ClinicalTrials.gov Registration Number: NCT02782585.

PMID- 29037632
TI  - Comparison of acute effects of superficial and deep dry needling into trigger
      points of suboccipital and upper trapezius muscles in patients with cervicogenic
      headache.
AB  - OBJECTIVE: The purpose of this study was to compare the acute effects of
      superficial and deep dry needling into trigger points of suboccipital and upper
      trapezius muscles in patients with cervicogenic headache. METHODS: Thirty
      participants (8 men, 22 women) aged 19-60 years (mean age +/- SD, 39 +/- 10 y)
      with a clinical diagnosis of cervicogenic headache were randomly divided into
      superficial and deep groups. Headache index, trigger points tenderness, cervical
      range of motion (CROM), functional rating index was assessed at baseline,
      immediate and 1 week after the treatment. RESULTS: Two approaches of dry needling
      showed reduction in headache index and trigger points tenderness. Deep dry
      needling showed greater improvement of cervical range of motion (p < 0.001) and
      functional rating index (p < 0.01). CONCLUSION: The application of dry needling
      into trigger points of suboccipital and upper trapezius muscles induces
      significant improvement of headache index, trigger points tenderness, functional
      rating index and range of motion in patients with cervicogenic headache. Deep dry
      needling had greater effects on CROM and function.

PMID- 29037633
TI  - Pilates increases the isokinetic muscular strength of the knee extensors and
      flexors in elderly women.
AB  - INTRODUCTION: Pilates has been shown to be effective for increasing muscle
      strength in older adults, however, some variables have not yet been explored.
      OBJECTIVE: Investigate the effects of Pilates on the isokinetic muscular strength
      of the knee extensors and flexors at 60 degrees /s, in elderly women. METHOD:
      Thirty-two women were randomized into two groups: control group (CG, n = 16, age
      = 64.2 +/- 0.8 years; BMI = 25.0 +/- 1.2 kg/m2), and experimental group (EG, n =
      16, age = 63.6 +/- 1.0 years, BMI = 24.7 +/- 1.3 kg/m2). Isokinetic evaluation of
      the knee extensor and flexor muscles was performed at 60 degrees /s, pre- and
      post-intervention, considering the peak torque (N.m) and total work (J) for the
      right and left lower limbs. The CG participated in static stretching and the EG
      in Pilates sessions, twice a week for 12 weeks. RESULTS: The results demonstrated
      that the EG presented a significant improvement (p < 0.01) in all tests
      performed, when comparing the pre- and post-intervention (intragroup), with an
      effect size (Cohen's d) reaching 2.03 and 1.33 for the knee flexor and extensor
      muscles respectively. Comparing the CG and EG (intergroup), post-intervention, a
      significant improvement was observed (p <= 0.01) in favor of the EG for all
      variables, with an effect size (Cohen's d) reaching 1.59 and 1.15 for the knee
      flexor and extensor muscles respectively. CONCLUSION: The results indicated that
      12 weeks of Pilates increases the isokinetic muscular strength of the knee
      extensors and flexors in elderly women and can be considered for this purpose
      when prescribing physical exercise programs.

PMID- 29037634
TI  - Pilot study: Post-operative rehabilitation pathway changes and implementation of
      functional closed kinetic chain exercise in total hip and total knee replacement
      patient.
AB  - OBJECTIVE: The aim of this study was to assess the feasibility of introducing a
      functional closed kinetic chain exercise program to an acute care setting to
      reduce length of hospital stay and assess tolerance to exercise immediately
      following total hip or total knee arthroplasty. METHODS: A protocol change
      implementing a functional closed kinetic chain based exercise program, post total
      hip (n = 535) and total knee (n = 695) arthroplasty, was performed at Windsor
      Regional Hospital Ouellette Campus in Windsor, Ontario Canada. A chart review was
      performed to compare the length of stay, post-surgery, of the new protocol to the
      length of stay of the previous range of motion and open kinetic chain based
      protocols of the previous two years. RESULTS: A significant (P-value <0.05)
      number of total hip and total knee arthroplasty patients reduced the length of
      hospital stay to less than 4 days using the closed kinetic chain program.
      CONCLUSION: Evidence suggests that closed kinetic chain exercises are tolerated
      in the acute care setting and may be useful in reducing hospital length of stay
      post total hip and total knee arthroplasty.

PMID- 29037635
TI  - The immediate effect of talocrural joint manipulation on functional performance
      of 15-40 years old athletes with chronic ankle instability: A double-blind
      randomized clinical trial.
AB  - OBJECTIVE: To evaluate the immediate effect of talocrural joint manipulation
      (TCJM) on functional performance of athletes with chronic ankle instability
      (CAI). PARTICIPANTS: Forty athletes (18males, 22females) with CAI divided into
      TCJM group (n = 20) and sham manipulation group (n = 20). INTERVENTION: TCJM was
      performed as a quick thrust on the involved talus, in the posterior direction.
      Sham manipulation was maintaining the same position, without any thrust. MAIN
      OUTCOME MEASURES: Functional performance of athletes was assessed with single leg
      hop; speed and Y balance tests, before and after the interventions. RESULTS: All
      functional tests evaluated in this study improved significantly after TCJM (p
      value<0.05). These findings were not seen in the control group. Between-group
      comparisons also showed significant changes for all the measurements after the
      interventions (p < 0.05). CONCLUSIONS: TCJM can significantly increase the
      functional performance of athletes with CIA and can be an effective supplementary
      treatment for these subjects. However, this was a pre-post study and future
      studies with long-term follow-ups may provide more reliable results about the
      long-term effectiveness of this type of treatment.

PMID- 29037636
TI  - Effects of Kinesio Taping(r) on knee function and pain in athletes with
      patellofemoral pain syndrome.
AB  - OBJECTIVE: To compare the knee performance and pain in athletes with
      patellofemoral pain syndrome (PFPS) before and after applying Kinesio Tape(r)
      (KT) on vastus medialis obliquus (VMO) muscle. PARTICIPANTS: Fifteen participants
      (10 females, five males) with unilateral PFPS were examined and compared under
      taped and untaped conditions. INTERVENTION: VMO of the involved leg was taped
      from origin to insertion, with 75% of KT's maximal length tension. MAIN OUTCOME
      MEASURES: Maximal eccentric and concentric peak torques of quadriceps were
      measured at 60 and 180 degrees /s angular velocities by an isokinetic
      dynamometer. Functional performance and pain were evaluated by functional tests
      (step-down and bilateral squat) and visual analog scale, respectively. RESULTS:
      Paired t-test showed statistically significant increase in VMO peak torque and
      also repetition of step-down test and bilateral squat after using KT. Pain
      intensity was also decreased significantly following KT application (p < 0.05).
      CONCLUSIONS: KT application over VMO can decrease pain and improve the functional
      performance, generally and quadriceps muscle strength, particularly, in athletes
      with PFPS. However, more research is needed to evaluate the long-term effects of
      this therapeutic procedure.

PMID- 29037637
TI  - Effect of yoga on the menstrual pain, physical fitness, and quality of life of
      young women with primary dysmenorrhea.
AB  - The aim of the present study was to investigate effect of specially designed yoga
      program on the menstrual pain, physical fitness, and quality of life (QOL) of non
      athlete women with primary dysmenorrhea (PD) aged 18-22 years. Thirty-four
      volunteers were randomly assigned into control and yoga groups. Menstrual pain,
      physical fitness, and QOL were evaluated at baseline and at the end of the 12
      week study period. The yoga group was asked to practice yoga for 30 min per day,
      twice a week, for 12 weeks at home, while the control group did not receive any
      form of exercise over the study period. There were significant improve in
      menstrual pain, physical fitness, and QOL in the yoga group more than the control
      group. Therefore, this specially designed yoga program may be a possible
      complementary treatment for PD.

PMID- 29037638
TI  - The effects of Clinical Pilates exercises on patients with shoulder pain: A
      randomised clinical trial.
AB  - AIM: The purpose of this study was to determine the effect of Clinical Pilates
      exercises on patients with shoulder pain. MATERIAL AND METHODS: Thirty-three
      patients, experiencing shoulder pain continuously for at least four weeks were
      selected as study subjects. The patients were randomly divided into two groups,
      namely Clinical Pilates exercise (n = 17) group and conventional exercise (n =
      16) group. The patients were treated for five days a week, the total treatment
      being carried out for 10 days. The assessment of pain and disability amongst the
      patients were done at the baseline and at the end of the treatment sessions,
      using Visual Analogue Scale (VAS) and Shoulder Pain and Disability Index (SPADI).
      RESULTS: The clinical Pilates exercise group showed a significant improvement in
      all scores used for assessment (p < 0.05), while the conventional exercise group
      demonstrated a significant improvement only in the SPADI total score (p < 0.05).
      A comparison of scores for the VAS, SPADI-Pain and SPADI-Total between the two
      groups, revealed a significant improvement in the Clinical Pilates exercise group
      (p < 0.05). CONCLUSION: It was demonstrated by the study that Clinical Pilates
      exercise is an efficient technique for patients experiencing shoulder pain, as it
      helps reduce pain and disability among them.

PMID- 29037639
TI  - Reliability of kinematic measures in subjects with anterior cruciate ligament
      deficiency during dual-task walking.
AB  - OBJECTIVE: To define the throughout within- and between-day reliability of gait
      parameters in single - and dual-task conditions in subjects with and without
      anterior cruciate ligament deficiency (ACLD). METHODS: Fourteen subjects with
      ACLD and 14 healthy subjects completed a walking task on a treadmill with three
      levels of velocity (self-selected, high and low), with or without performing an
      auditory Stroop task over two sessions each 3-5 days apart. The gait kinematic
      parameters, including maximum and minimum hip flexion, total hip range of motion,
      maximum and minimum knee flexion and total knee range of motion were recorded
      using a motion analysis system. The intraclass correlation coefficient (ICC), the
      standard error of measurement (SEM), and the coefficient of variation (CV) were
      used to determine inter- and intrasession reliability of kinematic and cognitive
      measures. RESULTS: ICCs for ACLD group in dual-task and single task conditions
      ranged between 0.50 to 0.93 and 0.53 to 0.93, respectively. ICC values for
      healthy groups in dual-task and single task conditions ranged between 0.36 to
      0.90 and 0.39 to 0.87, respectively. When comparing relative reliability across
      kinematic variables in different velocities, ICC values were generally identical
      in all three levels of velocity. CONCLUSION: The findings suggest that dual
      tasking could also be applied reliably for the assessment of functional
      activities in subjects with and without ACLD.

PMID- 29037640
TI  - Effect of movement control and stabilization exercises in people with extension
      related non -specific low back pain- a pilot study.
AB  - BACKGROUND: Exercise is considered an effective treatment strategy for non
      specific chronic low back pain (NSCLBP).background In spite of the wide use of
      exercise protocols, it is not clear what type of exercise is more effective in
      decreasing pain, disability and normalizing muscle activation patterns in people
      with chronic low back pain. OBJECTIVES: To assess the effects of two exercise
      protocols (stabilization vs movement control) on pain and disability scores and
      the flexion relaxation ratio (FRR) of lumbar multifidus (LM) and iliocostalis
      lumbarum pars thoracic (ICLT) in people with extension related non-specific
      chronic low back pain. STUDY DESIGN: Pilot randomized control trial. METHODS: 32
      subjects with active extension pattern chronic low back pain (stabilization group
      = 16, movement control group = 16) participated in this study. Treatment groups
      received 4 weeks of exercise therapy. Outcomes were based on pain score (Numeric
      rating Scale-NRS), disability (Oswestry Disability Index- ODI) and FRR of the LM
      and ICLT. RESULTS: Four people dropped out of the study in each group for reasons
      unrelated to the protocols of the study. Pain and disability reduced in both
      groups, with no significant difference between the groups. The FRR of LM did not
      change in either treatment group after treatment. However, the FRR of ICLT was
      significantly increased after treatment in the movement control group.
      CONCLUSION: Both movement control and stabilization exercises reduced pain and
      disability in the short-term among people with extension pattern NSCLBP, with no
      difference in effectiveness between the groups. However, movement control
      exercises were more effective in normalizing back muscle activation patterns than
      stabilization exercises.

PMID- 29037641
TI  - Impact of osteopathic therapy on proprioceptive balance and quality of life in
      patients with dizziness.
AB  - The aim of the study was to evaluate the efficacy of osteopathic manipulative
      treatment (OMT) in patients with Benign-Paroxysmal-Positional Vertigo (BPPV).
      Thirty-one patients with BPPV were randomly assigned into two groups: 19 patients
      received osteopathic treatments (TG) and 12 patients received sham therapy (SG),
      both in four weekly sessions. Before the first and the last treatment, those
      patients were evaluated using Dizziness Handicap Inventory (DHI) and
      stabilometric platform to assess lifestyle modification and balance functions.
      After the treatment session, TG compared to SG showed an improvement in DHI
      global (p = 0.02), functional (p = 0.03) and physical (p = 0.03) components, as
      well as a reduction of swinging area (p = 0.02). An association between swinging
      area and lifestyle measures (global [r = 0.53; p = 0.02]; functional [r = 0.50; p
      = 0.03]; physical [r = 0.60; p = 0.01]) changes were found in TG. These findings
      suggest that OMT could be a useful approach to reduce imbalance symptoms and to
      improve the quality of life in patients suffering from dizziness.

PMID- 29037642
TI  - Rebound boots change lower limb muscle activation and kinematics during different
      fitness exercises.
AB  - The purpose of this study was to evaluate electromyography and kinematic
      parameters of the lower limbs using rebound boots (RB) and barefoot during a gym
      workout. This information can be helpful to practitioners to schedule
      rehabilitation and training programs. Ten women (25 +/- 9 years) volunteered for
      the study; inclusion criteria were as follows: subjects must have experienced the
      use of RB and the analyzed exercises for at least 6 months, and have no previous
      injuries in the lower limbs. Seven exercises were performed for 30 s with the RB
      and subsequently barefoot. Data from muscle activation of vastus lateralis (VL),
      biceps femoris (BF), lateral gastrocnemius (LG) and 2D kinematics were collected.
      The use of RB triggered postural changes, characterized by greater hip extension
      (in 4 of the exercises) and knee extension (in 6 of the exercises) for the
      landing. RB reduced activation mainly in LG (in 6 of the exercise) while no
      changes were observed for VL (except in exercise 1) and BF. RB change kinematics
      and muscle activation suggesting changes in the way the legs absorb and transmit
      force during jumps. LG was the main muscle affected by the use of RB.

PMID- 29037643
TI  - Immediate effect of common peroneal nerve electrical stimulation on quadriceps
      muscle arthrogenic inhibition in patients with knee osteoarthritis.
AB  - OBJECTIVE: To investigate the immediate effect of electrical stimulation of the
      common peroneal nerve on the maximum voluntary activation of the quadriceps
      muscle in patients with knee osteoarthritis. METHODOLOGY: Fifteen subjects with
      knee osteoarthritis (mean age: 50.5 +/- 13 years) participated in this study. To
      measure the arthrogenic inhibition ratio of quadriceps, a burst of electrical
      stimulation was superimposed on the maximum voluntary contraction, and the
      percentage of change in the force production was computed. The same measurement
      was also performed with concurrent electrical stimulation of the common peroneal
      nerve. RESULTS: All the patients with knee osteoarthritis showed significant
      arthrogenic inhibition of the quadriceps muscle. The stimulation of the common
      peroneal nerve was able to reduce this inhibition and increase the capacity of
      the muscle to produce a significantly higher knee extension force (p = 0.028).
      CONCLUSIONS: Electrical stimulation of the common peroneal nerve concurrent with
      the maximum voluntary effort can remove the arthrogenic inhibition of the
      quadriceps muscle in patients with knee osteoarthritis. This finding could have
      clinical implications in the management of patients with knee disorders.

PMID- 29037644
TI  - Low handgrip strength levels among adolescents in a city in southern Brazil.
AB  - OBJECTIVE: To estimate the prevalence of low handgrip strength (HGS) levels and
      sociodemographic characteristics, health behaviours and body fatness status
      related in adolescents. METHOD: Cross-sectional epidemiological study with 636
      adolescents aged 14-19 years in a city in southern Brazil. HGS was measured by
      dynamometer. Sociodemographic and behavioural data were collected using self
      report questionnaires. Body mass and height was measured by Body Mass Index.
      RESULTS: Prevalence of low HGS levels was 47% (63.5% boys, 37.7% girls). Boys
      aged 14-16 years were more likely to have low HGS levels. Girls who were of
      higher socioeconomic status and who were less physically active were more likely
      to have low HGS levels. Overweight girls were less likely to have low HGS levels.
      CONCLUSIONS: High prevalence of low HGS levels was observed in adolescents.
      Increased HGS levels should be focused on younger boys and normal-weight girls
      with higher socioeconomic status and lower levels of physical activity.

PMID- 29037645
TI  - Postural insoles on gait in children with cerebral palsy: Randomized controlled
      double-blind clinical trial.
AB  - The aim of the present study was to assess the effect of postural insoles on gait
      performance in children with Cerebral Palsy (CP). Twenty four children between
      four and 12 years of age were randomly allocated either the control group (n =
      12) or experimental group (n = 12). The control group used placebo insoles and
      the experimental group used postural insoles. Three-dimensional gait analysis was
      performed under three conditions: barefoot, in shoes and in shoes with insoles.
      Three evaluations were carried out: 1)immediately following placement of the
      insoles; 2)after three months of insole use; and 3)one month after suspending
      insole use. Regarding the immediate effects and after three months use of insole,
      significant improvements in gait velocity and cadence were found in the
      experimental group, along with an increase in foot dorsiflexion, a reduction in
      knee flexion and a reduction in internal rotation. Conversely, these changes were
      not maintained in the third assessment, one month after withdrawal of the
      insoles. The use of postural insoles led to improvements in gait performance in
      children with CP.

PMID- 29037646
TI  - Impact of physical growth, body adiposity and lifestyle on muscular strength and
      cardiorespiratory fitness of adolescents.
AB  - OBJECTIVE: To investigate the impact of physical growth, body adiposity and
      lifestyle on cardiorespiratory fitness and muscle strength of pubescent and post
      pubescent adolescents. METHODS: Cross-sectional study with 1132 adolescents (14
      19 years) in Brazil. Aerobic fitness was measured using the modified Canadian
      Aerobic Fitness Test. Muscle strength was assessed using manual dynamometer.
      Maturational stages were defined through the Tanner criteria. RESULTS: Boys at
      pubertal maturation stage showed higher VO2max values than those at the post
      pubertal stage when the influence of body adiposity and lifestyle was
      disregarded. Girls at pubertal maturation stage showed higher VO2max values than
      those in the post-pubertal stage when the influence of age was disregarded. For
      muscle strength, no significant differences were found. CONCLUSIONS: The
      variables that influence the association between VO2max and maturational stage
      are different for boys and girls.

PMID- 29037647
TI  - A critical overview of the current myofascial pain literature - October 2017.
AB  - In this overview of the myofascial pain literature, we have included several
      original contributions ranging from a study by Bowen and colleagues of trigger
      points in horses to the introduction of a new clinical entity of "laryngeal
      muscle myofascial pain syndrome in dysphonic patients." Minerbi and colleagues
      described for the first time the referred pain patterns of the longus colli
      muscle, while Casale and associates studied the spinal modulatory action of dry
      needling or acupuncture stimulation. Many dry needling articles are included in
      this overview with several recent outcome studies. Slowly, there is increasing
      scientific support for using dry needling for a variety of conditions. Several
      researchers explored specific aspects of dry needling, such as needle placements,
      whether eliciting a local twitch response is desired, and the role of
      psychological factors in post-needling soreness. Contributions originated in
      Australia, Belgium, Brazil, Canada, China, Germany, Greece, India, Israel, Italy,
      Korea, Portugal, Spain, Switzerland, Turkey, the UK, and the USA.

PMID- 29037648
TI  - Test-retest reliability of myofascial trigger point detection in hip and thigh
      areas.
AB  - BACKGROUND: Myofascial trigger points (MTrP's) are a primary source of pain in
      patients with musculoskeletal disorders. Nevertheless, they are frequently
      underdiagnosed. Reliable MTrP palpation is the necessary for their diagnosis and
      treatment. The few studies that have looked for intra-tester reliability of MTrPs
      detection in upper body, provide preliminary evidence that MTrP palpation is
      reliable. Reliability tests for MTrP palpation on the lower limb have not yet
      been performed. OBJECTIVE: To evaluate inter- and intra-tester reliability of
      MTrP recognition in hip and thigh muscles. DESIGN: Reliability study. SUBJECTS:
      21 patients (15 males and 6 females, mean age 21.1 years) referred to the
      physical therapy clinic, 10 with knee or hip pain and 11 with pain in an upper
      limb, low back, shin or ankle. METHODS: Two experienced physical therapists
      performed the examinations, blinded to the subjects' identity, medical condition
      and results of the previous MTrP evaluation. Each subject was evaluated four
      times, twice by each examiner in a random order. Dichotomous findings included a
      palpable taut band, tenderness, referred pain, and relevance of referred pain to
      patient's complaint. Based on these, diagnosis of latent MTrP's or active MTrP's
      was established. The evaluation was performed on both legs and included a total
      of 16 locations in the following muscles: rectus femoris (proximal), vastus
      medialis (middle and distal), vastus lateralis (middle and distal) and gluteus
      medius (anterior, posterior and distal). RESULTS: Inter- and intra-tester
      reliability (Cohen's kappa (kappa)) values for single sites ranged from -0.25 to
      0.77. Median intra-tester reliability was 0.45 and 0.46 for latent and active
      MTrP's, and median inter-tester reliability was 0.51 and 0.64 for latent and
      active MTrPs, respectively. The examination of the distal vastus medialis was
      most reliable for latent and active MTrP's (intra-tester k = 0.27-0.77, inter
      tester k = 0.77 and intra-tester k = 0.53-0.72, inter-tester k = 0.72,
      correspondingly). CONCLUSIONS: Inter- and intra-tester reliability of active and
      latent MTrP evaluation was moderate to substantial. Palpation evaluation can be
      used for clinical diagnosis of MTrP's in the hip and thigh muscles. SIGNIFICANCE:
      This study provides evidence that MTrP palpation is a moderately reliable
      diagnostic tool in the hip and thigh muscles and can be used in clinical practice
      and research.

PMID- 29037649
TI  - A comparison of the effect of the active release and muscle energy techniques on
      the latent trigger points of the upper trapezius.
AB  - BACKGROUND/AIM: The increasing use of computer in daily life has brought about
      numerous musculoskeletal problems. Impairments in the head, neck and shoulders
      are more common compared with the other parts of the body. The aim of this study
      was to compare the effect of two manual treatments in two separate groups, i.e.,
      active release technique (ART) and muscle energy technique (MET) on the latent
      trigger points (LTrPs) in the upper trapezius muscle. The set criteria in the
      study included the active range of cervical lateral flexion, pain intensity on
      the visual analog scale (VAS), and the upper trapezius muscle thickness. SUBJECTS
      AND METHODS: This clinical trial study assessed the outcome measures within and
      between groups before and after the intervention. The target population were 64
      (32 males, 32 females) participants who had been selected from among the staff
      members and the students of a rehabilitation school, and the employees of an
      engineering company who had LTrPs in their upper trapezius muscle and were from
      18 to 50 years old. RESULTS: The immediate effects of MET and ART on the patients
      of each groups with LTrPs in their upper trapezius muscle were increased active
      range of cervical lateral flexion (P < 0.001), decreased pain intensity on VAS (P
      < 0.05) and decreased thickness of the upper trapezius muscle (P < 0.01).
      CONCLUSION: Both manual techniques of ART and MET reduced the symptoms of LTrPs
      in the upper trapezius in the two groups equally, neither technique being
      superior to the other.

PMID- 29037650
TI  - The intra-rater reliability of locating and measuring the severity of latent
      trigger points in the quadriceps.
AB  - BACKGROUND: Trigger points (TrPs) in the lower-limb are under-investigated and
      may be a contributory factor in knee pathologies. OBJECTIVES: The purpose of this
      study was to establish the intra-rater reliability of assessing the location and
      severity of latent TrPs in the quadriceps. METHODS: Twenty-nine asymptomatic
      subjects were palpated for TrPs in the middle and quadriceps. The location and
      severity was then measured using the anatomical landmark system (ALS) and pain
      pressure threshold (PPT). The subject was re-tested the next day. RESULTS: The
      intra-class coefficient [ICC(3,1)] for the ALSs and PPTs were found to be
      reliable. Gender appears to be a factor in the severity of TrPs in the
      quadriceps. Females reported some of the features of TrPs more often than males
      (jump sign, twitch response, referred pain). CONCLUSION: Further investigation is
      needed to understand the relationship between TrPs around the knee and knee
      pathologies, particularly in females.

PMID- 29037651
TI  - Effect of ischemic compression for cervicogenic headache and elastic behavior of
      active trigger point in the sternocleidomastoid muscle using ultrasound imaging.
AB  - OBJECTIVES: To investigate the effect of ischemic compression on clinical
      outcomes of a cervicogenic headache and elastic behavior of myofascial trigger
      points. DESIGN: Randomized, controlled trial. SETTING: Outpatient headache
      clinic. SUBJECTS: 19 subjects with a cervicogenic headache originating from
      myofascial trigger point within the sternocleidomastoid muscle. INTERVENTIONS:
      Subjects were randomized in treatment group (n = 9) and control group (n = 10).
      Subjects in the treatment group received 4 sessions of ischemic compression in
      the myofascial trigger point region. MAIN MEASURES: Headache intensity,
      frequency, and duration, trigger point elastic modulus, trigger point area,
      pressure tolerance, and pressure pain threshold were assessed before and after
      treatment. RESULTS: Subjects in the treatment group compared with those in
      control group showed significant improvements in headache intensity (P = 0.002),
      headache frequency (P = 0.005), headache duration (P = 0.015), pressure tolerance
      (P < 0.001), pressure pain threshold (P = 0.039), and myofascial trigger point
      area (P = 0.017). Changes in myofascial trigger point elastic modulus did not
      reach a significant level (P > 0.05). CONCLUSION: The improvements in outcome
      measures suggest that ischemic compression may be effective in subjects with a
      cervicogenic headache associated with a myofascial trigger point in the
      sternocleidomastoid muscle. Data suggests that biomechanical properties of MTrP
      and severity of headache symptoms are not directly linked, and other mechanisms
      could be more influential in contributing to symptoms.

PMID- 29037652
TI  - The local twitch response during trigger point dry needling: Is it necessary for
      successful outcomes?
AB  - BACKGROUND: Myofascial trigger point (MTrP) injection and trigger point dry
      needling (TrPDN) are widely accepted therapies for myofascial pain syndrome
      (MPS). Empirical evidence suggests eliciting a local twitch response (LTR) during
      needling is essential. OBJECTIVE: This is the first review exploring the
      available literature, regardless of study design, on the neurophysiological
      effects and clinical significance of the LTR as it relates to reductions in pain
      and disability secondary to MTrP needling. METHODS: PubMed, MEDLINE, Science
      Direct and Google Scholar were searched up until October 2016 using terms related
      to trigger point needling and the LTR. RESULTS: and Discussion: Several studies
      show that eliciting a LTR does not correlate with changes in pain and disability,
      and multiple systematic reviews have failed to conclude whether the LTR is
      relevant to the outcome of TrPDN. Post needling soreness is consistently reported
      in studies using repeated in and out needling to elicit LTRs and increases in
      proportion to the number of needle insertions. In contrast, needle winding
      without LTRs to MTrPs and connective tissue is well supported in the literature,
      as it is linked to anti-nociception and factors related to tissue repair and
      remodeling. Additionally, the positive biochemical changes in the MTrP after
      needling may simply be a wash out effect related to local vasodilation. While the
      LTR during TrPDN appears unnecessary for managing myofascial pain and unrelated
      to many of the positive effects of TrPDN, further investigation is required.

PMID- 29037653
TI  - Adolescent idiopathic scoliosis: The Tethered Spine III: Is fascial spiral the
      key?
AB  - This article reports on an observational and treatment case series involving 22
      adolescents and preadolescents treated over a 15 year period who had or appeared
      to be developing idiopathic scoliosis (IS). Common patterns of muscle and fascial
      asymmetry were observed and treated. Most of these individuals had spinal area
      pain and the trigger points (TrPs) apparently responsible for this pain were
      located in muscles at some distance from the spine, yet referred pain to
      locations throughout the thoracolumbar spine. Asymmetries in tension in these
      muscles appear to tether the spine in such a way as to contribute to scoliotic
      curvatures. The most common pattern of asymmetrical muscle tension found in these
      individuals follows a particular spiral fascial plane and as the fascia in this
      spiral plane tightened, the scoliotic curvature appeared to increase. Evaluation
      also showed that 21 of 22 of these individuals have major ligamentous laxity and
      this may also have contributed to the development of scoliotic curvatures.
      Furthermore, each of these individuals has marked overpronation of the ankles,
      with arches that totally collapse when weight-bearing. Based on observation
      during the care of these 22 subjects, it appears that asymmetry in the degree of
      pronation may, in some individuals, be a contributing factor in the development
      of the spiral body organization involved in the development of scoliosis. Common
      patterns of joint dysfunction were also observed in many of these individuals.
      There were also some findings of significant muscle weaknesses that appeared to
      contribute to the development of the spiraling body organization. Treatment of
      the tethering of the spine from myofascial asymmetries and related joint
      dysfunction not only resulted in elimination of pain in almost all cases but
      also, in many cases resulted in significant reduction of scoliotic curvatures
      including reductions of rib humps. In other cases, it resulted in stabilization
      of scoliotic curvatures, and in some cases it may have slowed the rate of
      progression of curvatures. Stretching and strengthening exercises appeared to
      contribute to the stability of treatment gains. A segment of the treated
      population had atypical scoliotic curvatures that did not follow the typical
      spiral pattern. Even in these individuals, there were significant patterns of
      fascial restriction and joint dysfunction accompanying the curvatures. Prior
      traumatic injury was a common factor in almost all of these atypical cases.
      Treatment of myofascial TrPs and asymmetrical fascial tension and accompanying
      joint dysfunction is proposed as a useful approach to treating pain in
      adolescents who have or who appear to be developing scoliosis and to treating and
      controlling and/or decreasing many scoliotic curvatures. This case series is
      presented as a way to illuminate possible factors in the development of scoliosis
      and promising treatment strategies to address these factors and to eliminate pain
      and stabilize or decrease curvatures so that further research can more
      systematically evaluate the role of these factors. An addendum of two more cases
      is also included, because of the information that these cases add to the
      discussion and to treatment approaches. Including the addendum cases, 8 of the
      subjects had scoliosis as documented by x-rays. The other 16 appeared to be
      developing scoliosis according to criteria stated below.

PMID- 29037654
TI  - Systemic sclerosis: Association between physical function, handgrip strength and
      pulmonary function.
AB  - BACKGROUND: Systemic sclerosis (SSc) is a multisystem disease affecting the skin,
      respiratory system and skeletal muscles. In SSc patients, hand function
      disability is the major factor limiting daily activities. AIM: To evaluate the
      association of physical function with handgrip strength and pulmonary function in
      SSc patients. A further aim was to assess the relationship between handgrip
      strength and pulmonary function in patients with SSc. METHOD: A cross-sectional
      study in which 28 patients with SSc underwent isometric handgrip strength (IHGS)
      measurement and pulmonary function tests and completed the Health Assessment
      Questionnaire Disability Index (HAQ-DI) to measure physical function. RESULTS:
      The HAQ-DI scores were associated with the IHGS (rs = -0.599, P = 0.001) and
      pulmonary function parameters, particularly the diffusion capacity for carbon
      monoxide (DLco; rs = -0.642, P = 0.0004). CONCLUSION: In patients with SSc, the
      degree of physical disability is associated with both hand grip strength and
      pulmonary function. However, there is no relationship between handgrip strength
      and pulmonary function in these patients.

PMID- 29037655
TI  - Differences in pressure pain threshold among men and women after foam rolling.
AB  - BACKGROUND: Rehabilitation professionals often prescribe foam rolling as an
      intervention to augment other manual therapies or as a warm-up or recovery after
      athletic activity. Currently, there is a gap in the literature regarding how foam
      rolling effects the pressure pain threshold (PPT) among men and women. PURPOSE:
      The purpose of this study was to examine the immediate effects of a foam rolling
      intervention on the ipsilateral agonist, antagonist, and contralateral muscle
      group PPT among men and women. SETTING: University kinesiology laboratory.
      PARTICIPANTS: Twenty healthy adults (M = 10, F = 10; mean age = 27.4 +/- 8.5
      years). RESEARCH DESIGN: Pre-test, post-test observational study. INTERVENTION:
      Video-guided foam roll intervention on the left quadriceps group. MAIN OUTCOME
      MEASURES: Ipsilateral quadriceps, ipsilateral hamstring, and contralateral
      quadriceps muscle PPT. RESULTS: Within group comparison for men, revealed a
      statistically significant effect of time on PPT for the left quadriceps
      (p=<0.001), left hamstring (p = 0.001), and right quadriceps (p=<0.001). For
      women, there was a statistically significant effect of time on PPT for the left
      quadriceps (p = 0.001), left hamstring (p = 0.007), and right quadriceps
      (p=<0.001). No significant difference in PPT between men and women were found for
      the left quadriceps (p = 0.31), left hamstring (p = 0.13), and right quadriceps
      (p = 0.070) muscle groups. CONCLUSIONS: These finding suggest that foam rolling
      can immediately reduce PPT in the ipsilateral agonist, antagonist, and
      contralateral muscle groups among men and women. Future investigations are needed
      to determine the long-term effects of foam rolling on PPT among sexes.

PMID- 29037656
TI  - Demystifying shoulder pain with electrodiagnosis and musculoskeletal ultrasound
      imaging.

PMID- 29037657
TI  - Procedures of assessment on the quantification of thoracic kyphosis and lumbar
      lordosis by radiography and photogrammetry: A literature review.
AB  - The quantification of thoracic kyphosis and lumbar lordosis can be assessed in
      different ways; among them radiography and photogrammetry. However, the
      assessment procedures are not consistent in the literature for either method. The
      objective of this study was to conduct a literature review about postural
      assessment through radiography and photogrammetry, for delineating the procedures
      for both methods. In total 38 studies were selected by an online search in the
      MEDLINE and LILACS databases with the keywords: radiograph and posture, postural
      alignment, photogrammetry or photometry or biophotogrammetry. For the
      radiographic method, the results showed divergences in arm positioning and in the
      calculation of thoracic and lumbar angles. The photogrammetry demonstrated
      differences in relation to the camera, tripod, plumb line and feet positioning,
      angle calculation, software utilization, and the use of footwear. Standardization
      is proposed for both methods to help establish normative values and comparisons
      between diagnoses.

PMID- 29037658
TI  - Simple artificial training device for respiratory muscle strength and lung
      volumes in healthy young male and female subjects: A pilot study.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficiency of a simple
      artificial device for respiratory muscle strength training and lung volumes using
      either combined or non-combined exercise with elastic bands in healthy young
      participants. METHODS: Forty healthy young participants (20 male and 20 female)
      aged 19-24 years old were randomized into two main experiments with four sub
      groups; (1) artificial device (n = 10) & standard device (n = 10) training, and
      (2) artificial device training combined with elastic band (EB) exercise (n = 10)
      & standard device training combined with EB (n = 10) exercise. Respiratory muscle
      strength with maximal peak inspiratory pressure (PImax), and lung volumes; tidal
      volume (TV), inspiratory reserve volume (IRV), expiratory reserve volume (ERV)
      and vital capacity (VC) were evaluated before and after training once daily for 3
      weeks. Moreover, the peak dyspnea score and vital sign parameters were compared
      between the experimental groups after final training. RESULTS: All parameters had
      no statistical differences (p > 0.5) between the training devices alone and those
      combined with EB exercise prior to any experiments. Results from the first
      experiment showed that training with an artificial device increased all
      parameters (PImax, VC, IRV, ERV) significantly (p < 0.05), except for TV, when
      compared to pre training results, which were the same as those in the standard
      device training group. No statistical difference was shown between these groups
      after the training period had been performed. Furthermore, results of applying
      artificial device training combined with EB exercise showed a significant
      increase in all parameters, except for TV, and they were the same as the
      increased results in training with the standard device combined with EB exercise.
      There was no significant difference of data between these groups after the
      training period. Finally, the results of peak dyspnea score and all vital sign
      parameters from using the artificial device, with or without EB exercise, showed
      no statistical difference when compared to use of the standard device.
      CONCLUSION: This study proposed that a simple artificial device can be used to
      train the respiratory muscle with or without elastic band exercise in healthy
      young subjects.

PMID- 29037659
TI  - The accuracy of wide-field ultrasound biomicroscopy in localizing extraocular
      rectus muscle insertions in strabismus reoperations.
AB  - PURPOSE: To compare the accuracy of widefield ultrasound biomicroscopy (UBM) with
      mechanical intraoperative measurements of the distance between rectus muscle
      insertions and the corneal limbus in strabismus reoperations. METHODS: Subjects
      with a history of horizontal rectus muscle surgery who required further surgery
      on horizontal rectus muscle(s) were recruited prospectively. All widefield UBM
      measurements were carried out under topical anesthesia using a 50 MHz linear
      probe without immersion cup and external caliper. The insertion angle distance
      was measured using the caliper tool of the UBM device; the actual muscle
      insertion distance from the limbus was considered to be the measured distance
      plus 1 mm. The distance from muscle insertion to the limbus was also measured
      intraoperatively. The results of UBM and surgical measurements were compared.
      RESULTS: A total of 28 subjects were recruited, and 53 horizontal muscles (30
      medial rectus, and 23 lateral rectus muscles) were included. The longest distance
      of the muscle insertion from limbus detectable on UBM was 13 mm for the medial
      rectus muscle and 15 mm for the lateral rectus muscle. In 38 muscles (71.7%) UBM
      and surgical measurements were within 1 mm of each other. Only in 1 muscle (1.9%)
      was the difference between measurements >2 mm (2.3 mm). The intraclass
      correlation coefficient was 0.87, demonstrating excellent agreement between
      measurements. Limit of agreement analysis demonstrated better agreement between
      measurements of medial rectus muscles and in consecutive exotropia cases.
      CONCLUSIONS: This study demonstrated good agreement between intraoperative and
      widefield UBM measurements of the muscle insertion-limbus distance in our patient
      cohort.

PMID- 29037660
TI  - NMDA receptor blockade specifically impedes the acquisition of incentive salience
      attribution.
AB  - Glutamatergic signaling plays an important role in learning and memory. Using
      Pavlovian conditioned approach procedures, the mechanisms that drive stimulus
      reward learning and memory have been investigated. However, there are instances
      where reward-predictive stimuli can function beyond being solely predictive and
      can be attributed with "motivational value" or incentive salience. Using a
      Pavlovian conditioned approach procedure consisting of two different but equally
      predictive stimuli (lever vs. tone) we investigated the role NMDA receptor
      function has in the attribution of incentive salience. The results revealed that
      the administration of MK-801, an NMDA receptor antagonist, during acquisition of
      Pavlovian conditioned approach promoted goal-tracking to a lever stimulus, while
      control animals learned to sign-track. Moreover, within the same animals, the use
      of a tone stimulus elicited goal-tracking responses that were unaffected by MK
      801 pretreatments. Furthermore, a lever CS that elicited sign-tracking served as
      a more robust conditioned reinforcer than a tone CS that elicited goal-tracking
      or a lever CS that elicited goal-tracking via MK-801 pretreatments. Collectively,
      these results demonstrate that NMDA receptor antagonism can alter the stimulus
      reward relationship learned and prevent the attribution of incentive salience,
      rather than impede general learning.

PMID- 29037662
TI  - Effects of pharmacological manipulation of the kappa opioid receptors on the
      aversive effects of nicotine.
AB  - Nicotine, an addictive component of tobacco smoke, produces both rewarding and
      aversive effects. Increasing the aversive effects of nicotine may help in
      promoting smoking cessation. However, neural targets mediating the aversive
      effects of nicotine have not been fully identified. In this study, we evaluated
      the role of kappa opioid receptors (KORs) in the aversive effects of nicotine
      (0.4 mg/kg, base; s.c.) using the nicotine-induced conditioned taste aversion
      (CTA) model in Wistar rats. The KORs were activated using the selective KOR
      agonist (+/-)U-50,488H (0, 0.03, 0.15 & 0.3mg/kg; s.c.) and inhibited using the
      KOR antagonist nor-binaltorphimine (nor-BNI; 0, 15 & 30mg/kg; s.c.) in separate
      groups of rats using a between-subjects design. Pretreatment with the KOR agonist
      (+/-)U-50,488H (0.3mg/kg) significantly increased aversion for the nicotine
      associated solution. Additionally, (+/-)U-50,488H (0.3mg/kg) on its own induced
      aversion to the flavored solution associated with it even in the absence of
      nicotine, suggesting that the KOR agonist induced increase in nicotine-induced
      aversion was an additive effect. Interestingly, administration of the KOR
      antagonist nor-BNI (30mg/kg) prior to conditioning with nicotine/saline, but not
      after conditioning with nicotine/saline, attenuated nicotine-induced aversive
      effects compared to saline controls. Taken together, these data suggest a role
      for KORs in the aversive effects of nicotine.

PMID- 29037661
TI  - Antisense oligonucleotide therapy rescues disruptions in organization of
      exploratory movements associated with Usher syndrome type 1C in mice.
AB  - Usher syndrome, Type 1C (USH1C) is an autosomal recessive inherited disorder in
      which a mutation in the gene encoding harmonin is associated with multi-sensory
      deficits (i.e., auditory, vestibular, and visual). USH1C (Usher) mice, engineered
      with a human USH1C mutation, exhibit these multi-sensory deficits by circling
      behavior and lack of response to sound. Administration of an antisense
      oligonucleotide (ASO) therapeutic that corrects expression of the mutated USH1C
      gene, has been shown to increase harmonin levels, reduce circling behavior, and
      improve vestibular and auditory function. The current study evaluates the
      organization of exploratory movements to assess spatial organization in Usher
      mice and determine the efficacy of ASO therapy in attenuating any such deficits.
      Usher and heterozygous mice received the therapeutic ASO, ASO-29, or a control,
      non-specific ASO treatment at postnatal day five. Organization of exploratory
      movements was assessed under dark and light conditions at two and six-months of
      age. Disruptions in exploratory movement organization observed in control-treated
      Usher mice were consistent with impaired use of self-movement and environmental
      cues. In general, ASO-29 treatment rescued organization of exploratory movements
      at two and six-month testing points. These observations are consistent with ASO
      29 rescuing processing of multiple sources of information and demonstrate the
      potential of ASO therapies to ameliorate topographical disorientation associated
      with other genetic disorders.

PMID- 29037663
TI  - Unilateral forelimb sensorimotor cortex devascularization disrupts the
      topographic and kinematic characteristics of hand movements while string-pulling
      for food in the rat.
AB  - String-pulling by the rat is a bimanual act, in which an upright animal retrieves
      a piece of food attached to the end of the string by downward hand-over-hand
      movements. The present study compared the movements of string-pulling, using
      topographic and kinematic measures of hand movement, in control rats and rats
      with unilateral sensorimotor motor cortex lesion produced by removal of the pia
      matter. In the first week following devascularization, the rhythmicity and
      accuracy of string-pulling movements decomposed; however, thereafter the rhythm
      of bilateral alternation was restored. Over 70days of testing, distance traveled
      decreased for both hands in the control and lesion groups, suggesting that both
      groups displayed an increase in string-pulling efficiency. Nevertheless, the
      lesion group exhibited more missed string contacts with the (contralateral-to
      lesion) hand and more grasps in which the string was hooked between the digits
      with both hands. In addition, an increase in mouth grasps was observed in the
      lesion group. Motion capture analyses revealed that the lesion group exhibited
      longer reach and withdraw movements and these movements were longer for the
      ipsilateral-to-lesion vs contralateral-to-lesion hand. Thus, although rhythmicity
      of string-pulling behavior recovers after sensorimotor cortex devascularization,
      the contralateral-to-lesion hand contributed less to string pulling and requires
      mouth grasps to stabilize the string for grasping. The results are discussed in
      relation to contemporary theories of the contributions of the forelimb motor
      cortex to skilled movement and the potential use of string-pulling as a therapy
      for brain injury.

PMID- 29037664
TI  - Simultaneous optimization of the ultrasound-assisted extraction for phenolic
      compounds content and antioxidant activity of Lycium ruthenicum Murr. fruit using
      response surface methodology.
AB  - Lycium ruthenicum Murr. (LR) is a functional food that plays an important role in
      anti-oxidation due to its high level of phenolic compounds. This study aims to
      optimize ultrasound-assisted extraction (UAE) of phenolic compounds and
      antioxidant activities of obtained extracts from LR using response surface
      methodology (RSM). A four-factor-three-level Box-Behnken design (BBD) was
      employed to discuss the following extracting parameters: extraction time (X1),
      ultrasonic power (X2), solvent to sample ratio (X3) and solvent concentration
      (X4). The analysis of variance (ANOVA) results revealed that the solvent to
      sample ratio had a significant influence on all responses, while the extraction
      time had no statistically significant effect on phenolic compounds. The optimum
      values of the combination of phenolic compounds and antioxidant activities were
      obtained for X1=30min, X2=100W, X3=40mL/g, and X4=33% (v/v). Five phenolic acids,
      including chlorogenic acid, caffeic acid, syringic acid, p-coumaric acid and
      ferulic acid, were analyzed by HPLC. Our results indicated that optimization
      extraction is vital for the quantification of phenolic compounds and antioxidant
      activity in LR, which may be contributed to large-scale industrial applications
      and future pharmacological activities research.

PMID- 29037665
TI  - Unit and internal chain profiles of maca amylopectin.
AB  - Unit chain length distributions of amylopectin and its phi, beta-limit dextrins,
      which reflect amylopectin internal structure from three maca starches, were
      determined by high-performance anion-exchange chromatography with pulsed
      amperometric detection after debranching, and the samples were compared with
      maize starch. The amylopectins exhibited average chain lengths ranging from 16.72
      to 17.16, with ranges of total internal chain length, external chain length, and
      internal chain length of the maca amylopectins at 12.49 to 13.68, 11.24 to 11.89,
      and 4.27 to 4.48. The average chain length, external chain length, internal chain
      length, and total internal chain length were comparable in three maca
      amylopectins. Amylopectins of the three maca genotypes studied here presented no
      significant differences in their unit chain length profiles, but did show
      significant differences in their internal chain profiles. Additional genetic
      variations between different maca genotypes need to be studied to provide unit-
      and internal chain profiles of maca amylopectin.

PMID- 29037666
TI  - Multi-class analysis for simultaneous determination of pesticides, mycotoxins,
      process-induced toxicants and packaging contaminants in tea.
AB  - This study attempts at uniting the analysis of four different classes of
      contaminants for both liquid and solid tea samples. A total of 32 compounds,
      classified as pesticides, mycotoxins, process-induced toxicants or packaging
      contaminants, were carefully chosen for their diversity of structures and
      physicochemical properties. The proposed method combines a sample treatment
      strategy coming from metabolomics with liquid chromatography analysis using a
      silica bonded C18-pentafluorophenyl column coupled to high resolution mass
      spectrometry. For tea brew, dilute and shoot method provides good quantification
      (70-120% recoveries and <20% RSD) for more than 80% of compounds. For tea leaves,
      strong matrix effects are observed, thus, matrix-matched calibration is required
      to reach good performances, i.e. 63% of compounds quantified and 81% detected at
      10ug/kg. Finally, method performances were evaluated against existing
      regulations, and it appears that 69% of contaminants are quantified and 91%
      detected at levels lower than their respective European regulation limits.

PMID- 29037667
TI  - Hexafluoroisopropanol-induced salt-free catanionic surfactant coacervate
      extraction method for determination of fluoroquinolones in milk samples.
AB  - Coacervation and phase separation were first reported in salt-free catanionic
      surfactant aqueous systems based on lauric acid (LA) and dodecyltrimethylammonium
      hydroxide (DTAOH), using hexafluoroisopropanol (HFIP) as a coacervate-inducing
      agent. The liquid-liquid two-phase separation occurs over a wide of LA/DTAOH
      molar ratios (78:22-0:100mol/mol) and total surfactant concentrations (5-200mmolL
      1) upon adding a small amount of HFIP (<10%, v/v). HFIP-induced salt-free
      LA/DTAOH catanionic surfactant system has much wider two-phase region than HFIP
      induced salt-containing sodium laurate/dodecyltrimethylammonium bromide system. A
      HFIP-induced LA/DTAOH coacervate extraction method was established and coupled to
      high-performance liquid chromatography-ultraviolet detector (HPLC-UV) for
      determination of fluoroquinolones (rufloxacin, ciprofloxacin, danofloxacin,
      enrofloxacin) in milk. Detection limits are from 0.3ngmL-1 to 1.4ngmL-1. Intra-
      and inter-day precisions (n=6) are in range of 4.5-8.3% and 5.8-10.7%,
      respectively. Recoveries are from 87.8% to 109.0%. The method, HFIP-induced salt
      free coacervate extraction with HPLC-UV, is suitable for detecting trace
      fluoroquinolones in milk.

PMID- 29037668
TI  - Measurement and characterization of external oil in the fried waxy maize starch
      granules using ATR-FTIR and XRD.
AB  - Concerns regarding increased dietary oil uptake have prompted efforts to
      investigate the oil absorption and distribution in fried starchy foods. In the
      present study, attenuated total reflection Fourier transform infrared (ATR-FTIR)
      spectroscopy, together with a chloroform-methanol method, was used to analyze the
      external and internal oil contents in fried starchy samples. The micromorphology
      of fried starchy samples was further investigated using scanning electron
      microscope (SEM), polarized light microscope (PLM) and confocal laser scanning
      microscopy (CLSM). The results indicated that large amounts of oil were absorbed
      in or within waxy maize starch, but the majority of oil was located near the
      surface layer of the starch granules. After defatting, the internal oil was
      thoroughly removed, while a small amount of external oil remained. As evidenced
      by the changes of the crystalline characteristics with the help of X-ray
      diffraction (XRD), the interaction between starch and lipids on the surface was
      confirmed to form V-type complex compounds during frying at high moisture.

PMID- 29037669
TI  - Lipid composition and emulsifying properties of Camelina sativa seed lecithin.
AB  - There is no information on the chemical composition of camelina seed lecithin;
      therefore, the objective of this study was to investigate the chemical
      composition and emulsifying properties of lecithin recovered from camelina seed
      oil by water (WDCL) and enzymatic degumming (EDCL) using phospholipase A1 (PLA1).
      The lecithin obtained by both WDLC and EDLC was rich in phosphatidylinositol
      (PI), and contents were 37.8 and 25.2wt%, respectively. Lecithin recovered by
      enzymatic degumming contained more lysophospholipids compared to water degumming.
      The saturated fatty acid content of the EDCL was significantly higher than that
      of the WDCL. Emulsions stabilized using EDCL resulted in the highest stability
      when deionized water was used as the aqueous phase (original pH); however, at
      pH=7.5, emulsions stabilized using EDCL and WDCL were less stable compared to the
      emulsion stabilized with soy lecithin. Results showed that camelina seed lecithin
      is a promising alternative PI-rich emulsifier for various food applications.

PMID- 29037670
TI  - Isolation and characterization of collagen extracted from channel catfish
      (Ictalurus punctatus) skin.
AB  - Channel catfish skin is a by-product from catfish fillet production. Collagens
      were extracted from catfish skins by: (1) acid; (2) homogenization-aided; and (3)
      pepsin-aided extraction methods. Kinetic analysis of extraction was performed.
      SDS-PAGE was carried out for all collagens extracted under different conditions.
      Protein solubility, zeta potential, circular dichroism and gel strength of the
      collagen extracted by three methods were studied to determine optimal extraction
      conditions. Protein recovery rate from minced skins extracted with pH 2.4 HCl
      containing 23.6KU/g pepsin was the highest (64.19%). SDS-PAGE showed that
      collagens extracted with different methods had different proteins ratio patterns,
      even though the molecular mass of collagen subunits were similar, 123 and 113KDa
      for alpha1 and alpha2 chains, 226KDa for beta chain and 338.5KDa for gamma chain,
      respectively. Channel catfish skin collagens were typical type I collagens and
      could have applications in food, medical and cosmetic industries.

PMID- 29037671
TI  - Blue mussel (Mytilus edulis) protein hydrolysate promotes mouse mesenchymal stem
      cell differentiation into osteoblasts through up-regulation of bone morphogenetic
      protein.
AB  - Seafood provides a range of health benefits due to its high-protein level. In
      this study, the osteogenic effect of blue mussel (Mytilus edulis) protein
      hydrolysates (BMPH) on osteoblast differentiation were examined using mouse
      mesenchymal stem cells (MSCs). A preparation we called BMPH<1kDa which showed the
      highest osteogenic effect in MSCs, was prepared by peptic hydrolysis. BMPH<1kDa
      treatment stimulated osteoblast differentiation with alkaline phosphatase (ALP)
      induction, osteocalcin and type I collagen activity as well as calcium
      deposition. Osteoblast differentiation stimulated by BMPH<1kDa treatment was
      achieved by expression of osteogenic lineage markers, such as bone morphogenetic
      protein-2 (BMP-2), and downstream signal and transcription factors, including p
      Smad1/5/8, Dlx5, runt-related transcription factor 2 (Runx2), and osterix.
      BMPH<1kDa activated phosphorylation of mitogen-activated protein kinases. Adding
      noggin, a BMP antagonist, inhibited BMPH<1 kDa-induced ALP activity in MSCs.
      Taken together, our results show that BMPH<1kDa promoted osteoblast
      differentiation by activating BMP-2.

PMID- 29037672
TI  - Rapid and non-invasive detection and imaging of the hydrocolloid-injected prawns
      with low-field NMR and MRI.
AB  - Method development for monitoring economically motivated food adulteration is
      pivotal for preventing health problems caused by illegal food additives. In this
      work, low-field nuclear magnetic resonance (LF-NMR) spectroscopy and magnetic
      resonance imaging (MRI) was applied for the detection and mapping of adulterated
      prawns injected with different hydrocolloids including gelatin, carrageenan,
      agar, amorophophallus konjac and xanthan gum. The characteristic T2 fitting
      curves were obtained which can be used to tell apart adulterated prawns from
      normal ones. Furthermore, the benefit from high quality LF-MRI images showed the
      major accumulation site of the hydrocolloids injected in prawn. The location of
      these injections was mainly confined to well resolved accumulation in brain
      region and three following subtle sites: back, tail and claws. Different
      hydrocolloids can be successfully distinguished in adulterated prawns with
      principal component analysis. Therefore, rapid, non-invasive and low-cost LF-NMR
      technique offers a powerful tool for the identification of hydrocolloids
      adulteration in real-time.

PMID- 29037673
TI  - Effect of (-)-epigallocatechin gallate (EGCG) extracted from green tea in
      reducing the formation of acrylamide during the bread baking process.
AB  - This is the first study to investigate the extent of reduction in acrylamide
      formation during baking with the addition of (-)-epigallocatechin gallate (EGCG)
      extracted from green tea, and to determine whether EGCG influences the texture
      and colour attributes of bread, or interacts with other ingredients. EGCG powders
      were added to white bread formulations at the concentrations of 3.3, 6.6 and
      9.9g.kg-1. The amount of acrylamide in the bread was analysed using liquid
      chromatography-mass spectrometry. EGCG addition significantly reduced the
      acrylamide formation by 37% compared to the control and decreased the moisture
      content of the bread by 6%. It did not affect its texture attribute, but
      increased the lightness and the yellowness and decreased the redness of bread
      crust (with contrasting results in crumb). It also decreased granule size and
      porosity. In conclusion, EGCG fortification is a feasible method to decrease
      acrylamide formation in baked bread.

PMID- 29037674
TI  - Structure of pyrodextrin in relation to its retrogradation properties.
AB  - Pyrodextrins were prepared by heating waxy maize starch at 170 degrees C and pH
      3.0 for 0.5, 1, 2, 3 and 4h. Structural changes of pyrodextrins were determined
      by gel permeation chromatography and 1H NMR. Gelatinization and retrogradation of
      pyrodextrins were measured by differential scanning calorimetry. The water
      solubility of pyrodextrins increased from 48.9 to 99.4% as heating time increased
      from 0.5 to 4h. The molecular size, melting enthalpy of pyrodextrin, and the
      degree of retrogradation decreased as pyrodextrin solubility increased. The level
      of 1,6-anhydro-beta-d-glucopyranose increased from 2.6 to 4.0% as the heating
      time increased from 0.5 to 4h. The degree of branching (DB) of pyrodextrins was
      increased from 8.8 to 14.4%, and the average chain length (CL) reduced from 7.2
      to 4.6. The increased level of new bonds and DB combined with reduced CL during
      the dextrinization explained the reduced extent of retrogradation of the
      pyrodextrin.

PMID- 29037675
TI  - Novel hydroxypyridinone derivatives containing an oxime ether moiety: Synthesis,
      inhibition on mushroom tyrosinase and application in anti-browning of fresh-cut
      apples.
AB  - A range of hydroxypyridinone derivatives were synthesized starting from kojic
      acid. Among them, 10 and 11 were found to possess the strongest inhibitory effect
      on monophenolase activity of mushroom tyrosinase, having IC50 values of 2.04 and
      1.60MUM, respectively. The IC50 values of 10 and 11 for the inhibition of
      diphenolase activity of mushroom tyrosinase were determined as 13.89 and 7.99MUM,
      respectively. Investigation of the inhibitory mechanism of these two compounds
      indicated that the inhibition was reversible and of a competitive-uncompetitive
      mixed type. The KI and KIS values of 10 were determined to be 24.84 and 32.54MUM,
      respectively, and the corresponding values for 11 being 18.07 and 21.34MUM,
      respectively. The effect of 11 on the browning process of fresh-cut apples was
      evaluated by measuring the color change and browning index. The results indicated
      that 11 had a significant effect on controlling the browning of fresh-cut apple
      slices.

PMID- 29037676
TI  - Optimization of extraction yield and antioxidant properties of Brassica oleracea
      Convar Capitata Var L. leaf extracts.
AB  - Effects of extraction time and solvent polarity on antioxidant properties of
      Brassica oleracea leaves were optimized by response surface methodology using a
      central composite design. Five extraction times (12, 24, 36, 48 and 60h) and
      solvent polarities (dipole moment - hexane: 0.0, diethyl ether: 2.80, ethyl
      acetate: 4.40, methanol: 5.10 and water: 9.0D) were selected for optimization.
      Response surface analysis of data showed a significant increase (p<0.05) in
      extract yield and antioxidant potential, based on total phenolic acids, reducing
      abilities and free radical scavenging capacities, in response to an increase in
      extraction time and solvent polarity. The optimal response was obtained using
      relatively polar solvents (4.40-9.00D) and prolonged extraction times (50-60h).
      This suggests that most of the phytochemical constituents of B. oleracea leaves
      are polar and possess strong antioxidant potential.

PMID- 29037677
TI  - Thermal stability and gel quality of myofibrillar protein as affected by soy
      protein isolates subjected to an acidic pH and mild heating.
AB  - Thermal stability and gel quality of myofibrillar protein were evaluated with
      regard to the addition of native soy protein isolates (SPI) and SPI subjected to
      acidic pH and mild heating (modified SPI). Compared with the control, the
      addition of modified SPI increased the compression force of the protein gel and
      decreased water loss (P<0.05). Differential scanning calorimetry results showed
      that an addition of 0.75% native SPI decreased the first transition temperature
      (P<0.05), and addition of 0.5% and 0.75% modified SPI exhibited no appreciable
      changes on it (P>0.05), indicating that a higher concentration of modified SPI
      would not damage the protein thermal stability. Moreover, the addition of
      modified SPI enhanced hydrogen bonding and disulphide linkages. Atomic force
      microscopy analysis revealed that the addition of modified SPI decreased the
      roughness of the mixed myofibrillar protein gels. Overall, modified SPI has the
      potential to improve myofibrillar protein gel texture and water holding capacity.

PMID- 29037678
TI  - Optimization of rice amylose determination by NIR-spectroscopy using PLS
      chemometrics algorithms.
AB  - Determining amylose content in rice with near infrared (NIR) spectroscopy,
      associated with a suitable multivariate regression method, is both feasible and
      relevant for the rice business to enable Process Analytical Technology
      applications for this critical factor, but it has not been fully exploited. Due
      to it being time-consuming and prone to experimental errors, it is urgent to
      develop a low-cost, nondestructive and 'on-line' method able to provide high
      accuracy and reproducibility. Different rice varieties and specific chemometrics
      tools, such as partial least squares (PLS), interval-PLS, synergy interval-PLS
      and moving windows-PLS, were applied to develop an optimal regression model for
      rice amylose determination. The model performance was evaluated by the root mean
      square error of prediction (RMSEP) and the correlation coefficient (R). The high
      performance of the siPLS method (R=0.94; RMSEP=1.938; 8941-8194cm-1; 5592-5045cm
      1; and 4683-4335cm-1) shows the feasibility of NIR technology for determination
      of the amylose with high accuracy.

PMID- 29037679
TI  - Development of spectrophotometric method for iron determination in fortified
      wheat and maize flours.
AB  - The determination of iron in fortified foods is mandatory by many global
      regulatory agencies. However, the spectroscopic techniques require elevated
      investments limiting their applicability especially in developing countries.
      Therefore, simple, viable and analytical methods with sufficient sensitivity can
      become an alternative. In this work, a sensitive, simple and viable
      spectrophotometry method to determine iron in wheat and maize flours was
      developed following a cloud point extraction (CPE) procedure. The analyte was
      first complexed with 2-(5-Bromine-2-pyridylazo)-5-diethylaminophenol (Br-PADAP)
      in the presence of the surfactant octylphenoxypolyethoxyethanol (Triton X-114).
      For the CPE optimization the variables: pH of the medium, stoichiometry of the
      complex, surfactant, and salt concentrations were evaluated. Linearity in the
      analytical blank was obtained by using the square root of absorbance (Abs) in
      order to adjust the residues of the curve. The precision was lower than 5% and
      the accuracy ranged from 97 to 101%. The limits of detection and quantification
      were 0.004MUgmL-1 and 0.01MUgmL-1, respectively. The method was applied to
      investigate the content of iron in 14 brands of fortified flours. The
      concentrations of iron varied from 0.435 to 3.62mg/100g and 0.570 to 3.15mg/100g
      in wheat and maize flour, respectively. The content of iron in all brands
      investigated in this study was approximately 10-fold lower than the value
      required by (ANVISA). The amount of iron in fortified foods was satisfactorily
      determined by using a simple, sensitive, and low cost spectrophotometric method.

PMID- 29037680
TI  - Structure characterisation of polysaccharides in vegetable "okra" and evaluation
      of hypoglycemic activity.
AB  - Okra is a widely accepted vegetable in subtropical and tropical regions due to
      the good palatability. However, the polysaccharide compositions remain unclear.
      In this work, the water extract of okra pod was prepared and the leading
      polysaccharide fraction was purified. The precise structural characteristics were
      identified. It was a polysaccharide "rhamnogalacturonan" as shown below, and the
      structure was different to previously reported rhamnogalacturonans. The
      hypoglycemic effect of rhamnogalacturonan was determined in vivo. By comparing
      with streptozotocin-induced diabetic mice group, the high-dose group showed
      decreased blood glucose level and glucose tolerance. The body weight of all
      groups were not significantly different. The results indicated that the
      rhamnogalacturonan was responsible for the hypoglycemic effect of okra.

PMID- 29037681
TI  - Improved analysis of anthocyanins and vitamin C in blue-purple potato cultivars.
AB  - Methods were optimized for extraction and quantification of anthocyanins (ACY)
      and vitamin C in potatoes. Acidified aqueous methanol (70%) was the optimal
      extraction solvent and freeze-drying significantly improved the extraction yield
      of ACY. The content of ACY varied widely in five potato cultivars from 0.42 to
      3.18mg/g dry weight, with the latter being the highest value found in the Finnish
      cultivar 'Synkea Sakari'. Compared with dithiothreitol (DTT), tris(2
      carboxyethyl) phosphine hydrochloride (TCEP) was more efficient in reducing
      dehydroascorbic acid (DHA) to ascorbic acid (AA) and for quantifying the content
      of total ascorbic acid (TAA). For raw potatoes, quantification of TAA after
      treatment with TCEP was more reliable than a direct analysis of AA, whereas AA
      can be analyzed directly in steam-cooked samples. The TAA contents in the three
      potato cultivars were around 0.30-0.35mg/g dry weight. The loss of AA in steam
      cooking was 24%.

PMID- 29037682
TI  - l-Lysine and l-arginine inhibit myosin aggregation and interact with acidic amino
      acid residues of myosin: The role in increasing myosin solubility.
AB  - The objective of this paper is to investigate the potential affecting mechanisms
      of l-lysine (Lys)/l-arginine (Arg) on myosin solubility. The results showed that
      both Lys and Arg increased the solubility of myosin at the examined pH values.
      Additionally, both Lys and Arg decreased the hydrodynamic size of myosin but
      increased the hydration capacity (HC), the surface aromatic hydrophobicity of
      myosin, the surface tension of the myosin solution and the absolute transfer free
      energy (TFE) of the major amino acids that constitute myosin. The results
      indicate that the properties of Lys or Arg that result in an inhibition of myosin
      aggregation and an interaction with hydrophobic amino acid residues may play
      important roles in increasing the myosin solubility. The results are attractive
      to the meat industry.

PMID- 29037683
TI  - Arsenic hyperaccumulation and speciation in the edible ink stain bolete
      (Cyanoboletus pulverulentus).
AB  - The edible ink stain bolete (Cyanoboletus pulverulentus) was found to
      hyperaccumulate arsenic. We analyzed 39 individual collections determined as C.
      pulverulentus, mostly from the Czech Republic. According to our results,
      concentrations of arsenic in C. pulverulentus fruit-bodies may reach 1300mgkg-1
      dry weight. In most collections, data for total and bioavailable arsenic in
      underlying soils were collected but no significant correlation between the soil
      arsenic content and arsenic concentrations in the associated fruit-bodies was
      found. Within the fruit-bodies, we found the majority of arsenic accumulated in
      the hymenium. Besides occasional traces of methylarsonic acid (MA), the arsenic
      speciation in all mushroom samples consisted solely of dimethylarsinic acid (DMA)
      and no inorganic arsenic was detected. Because of the carcinogenic potential of
      DMA, C. pulverulentus should not be recommended as an edible mushroom and its
      consumption should be restricted.

PMID- 29037684
TI  - Chitosan delays ripening and ROS production in guava (Psidium guajava L.) fruit.
AB  - Guava is a typically tropical fruit highly perishable with a short shelf-life due
      to intense metabolic activity after harvested. In attempt to minimize the
      problems related to the postharvest, we evaluated the physiochemical
      characteristics and antioxidant system in guava fruits under chitosan coating at
      concentrations of 1%, 2%, and 3% stored at 25 degrees C during 96h. The chitosan
      suppressed the respiratory rate, fresh weight loss, firmness and skin color with
      delay in the degradation of chlorophyll. In the treatment with 2% and 3% of
      chitosan in the solid soluble content and ascorbic acid were reduced; retarded
      the loss of titratable acidity during 96h after treatment. These treatment
      induced significant decreases in the phenylalanine ammonia-lyase activity and
      significantly increases of peroxidase Activity. Our results suggest that chitosan
      effectively prolongs the quality attributes in guava fruits after harvesting due
      to increases in the antioxidant processes, delaying the ripening during room
      temperature of storage.

PMID- 29037685
TI  - Microencapsulation of Thai rice grass (O. Sativa cv. Khao Dawk Mali 105) extract
      incorporated to form bioactive carboxymethyl cellulose edible film.
AB  - Microencapsulation was investigated to enhance the stability of Thai rice grass
      extract. Microencapsulated powder (MP) was formed using total solid of extract
      solution and maltodextrin ratios of 1:4 (MP 1:4) and 1:9 (MP 1:9). The absence of
      an endothermic peak for both MPs confirmed all extract solutions were coated with
      maltodextrin. MP 1:9 had a lower total phenolic content (TPC) but was higher in
      antioxidant capacity than MP 1:4. Moreover, the TPC of the MPs slightly decreased
      (70.02-93.04%) during storage at 10, 30 and 70 degrees C for 30d. Comparatively,
      the TPC of the extract solution significantly decreased from 100% down to 20.8%,
      11.2% and 8.6% at 10, 30 and 70 degrees C, respectively. Therefore, MP 1:9
      incorporated with blended carboxymethyl cellulose film increased the water
      barrier and the TPC. This film can serve as a bioactive biodegradable packaging
      material to reduce plastic packaging in the food industry.

PMID- 29037686
TI  - Identification and biological activities of carotenoids from the freshwater alga
      Oedogonium intermedium.
AB  - The chemical and biological properties of carotenoids in the freshwater alga
      Oedogonium intermedium were investigated in this study. Carotenoids were
      extracted from the alga by dichloromethane and purified by saponification. The
      carotenoid content was determined both spectrometrically and by HPLC, the
      carotenoids identified by HPLC-PDA-APCI-IT-TOF-MS and the extracts analysed for
      several health-related bioactivities. The crude and saponified extracts contained
      3,411.2+/-20.7 and 2,929.6+/-5.9ug carotenoids/g dry algal biomass, respectively.
      Seven major carotenoids were identified, namely neoxanthin, 9'-cis-neoxanthin,
      loroxanthin, violaxanthin, lutein, alpha-carotene and beta-carotene, which were
      present in similar amounts in the alga. Both the crude and saponified carotenoid
      extracts exhibited significant antioxidant activities as well as potent
      inhibitory effects against several metabolically important enzymes including
      alpha-amylase, alpha-glucosidase, pancreatic lipase and hyaluronidase, but they
      were poor inhibitors of angiotensin converting enzyme (ACE). Oedogonium could be
      an important new source of carotenoids, specifically loroxanthin, which is
      lacking in terrestrial plants.

PMID- 29037687
TI  - Enhanced dispersion stability and heavy metal ion adsorption capability of
      oxidized starch nanoparticles.
AB  - Starch nanoparticles (SNPs) have attracted much research interest recently due to
      their biodegradability and biocompatibility. However, practical utilization of
      SNPs is generally restricted due to their weak colloid stability and reduced
      functionality. In this work, SNPs were functionally modified by sodium
      hypochlorite (1-5% active chlorine based on dry SNPs weight). The degree of
      modification, particle size, stability, and adsorption characteristics of the
      SNPs were systematically investigated. The results showed that as the active
      chlorine concentration increased, the carbonyl and carboxyl contents increased to
      0.150% and 0.855%, respectively. Compared with SNPs, the zeta potential value of
      SNPs modified with 5% active chlorine increased significantly (p<0.05) from -13
      to -31mV and the dispersion stability of modified SNPs was remarkably improved.
      Moreover, modified SNPs exhibited high adsorption capacities for Pb2+ and Cu2+,
      suggesting that they could be employed as a novel absorbent for removal of heavy
      metal ions.

PMID- 29037688
TI  - Production of phytotherapeutics from broccoli juice by integrated membrane
      processes.
AB  - An integrated membrane process for the recovery and concentration of
      phytotherapeutics in broccoli juice was investigated to develop a natural product
      that could be of interest for food and/or pharmaceutical industry. Following a
      pretreatment step to remove suspended solids, the juice was ultrafiltered through
      a 50kDa MWCO polyethersulfone membrane. The permeate stream was further
      concentrated by osmotic distillation up to 42.6 degrees Brix. During
      ultrafiltration, a complete recovery of sulforaphane, malic acid and citric acid
      was achieved, where total phenolic content and ascorbic acid were recovered at a
      ratio of 94.5 and 92.4%, respectively. All the bioactive compounds identified in
      broccoli juice was well preserved during subsequent 6-fold concentration by
      osmotic distillation. No significant difference was observed in total antioxidant
      activity of the juice throughout the operation. The proposed integrated membrane
      process has shown promising potential to produce a natural concentrate enriched
      in phytotherapeutics of the broccoli juice.

PMID- 29037689
TI  - Intra-regional classification of grape seeds produced in Mendoza province
      (Argentina) by multi-elemental analysis and chemometrics tools.
AB  - The feasibility of the application of chemometric techniques associated with
      multi-element analysis for the classification of grape seeds according to their
      provenance vineyard soil was investigated. Grape seed samples from different
      localities of Mendoza province (Argentina) were evaluated. Inductively coupled
      plasma mass spectrometry (ICP-MS) was used for the determination of twenty-nine
      elements (Ag, As, Ce, Co, Cs, Cu, Eu, Fe, Ga, Gd, La, Lu, Mn, Mo, Nb, Nd, Ni, Pr,
      Rb, Sm, Te, Ti, Tl, Tm, U, V, Y, Zn and Zr). Once the analytical data were
      collected, supervised pattern recognition techniques such as linear discriminant
      analysis (LDA), partial least square discriminant analysis (PLS-DA), k-nearest
      neighbors (k-NN), support vector machine (SVM) and Random Forest (RF) were
      applied to construct classification/discrimination rules. The results indicated
      that nonlinear methods, RF and SVM, perform best with up to 98% and 93% accuracy
      rate, respectively, and therefore are excellent tools for classification of
      grapes.

PMID- 29037691
TI  - Ageing and retail display time in raw beef odour according to the degree of lipid
      oxidation.
AB  - This study aims to assess the changes in beef aroma over time when steaks from
      pre-aged knuckles are stored in retail display under high oxygen conditions for
      15 or 22days in vacuum conditions. Odorous volatile compounds were analysed by
      solid-phase microextraction/gas chromatography-mass spectrometry. Results were
      grouped as low, medium and high oxidative groups according to thiobarbituric acid
      reactive substances values after 9days of display. The intensity of off-odours in
      the raw meat increased with ageing and display time and oxidative groups. Based
      on correlations between the variables and regressions of the compounds through
      display, eight compounds were proposed as odour shelf-life markers. Among them,
      five were most sensitive and precise in all oxidative groups: 1-hexanol in meat
      aged for 15days, ethyl- octanoate and 2-pentylfuran in meat aged for 22days, and
      pentanoic and hexanoic acids in the two studied ageing times.

PMID- 29037690
TI  - Multi-response modeling of reaction-diffusion to explain alpha-galactoside
      behavior during the soaking-cooking process in cowpea.
AB  - A modelling approach was developed to better understand the behavior of the
      flatulence-causing oligosaccharides in cowpea seeds during isothermal water
      soaking-cooking process. Concentrations of verbascose, stachyose and raffinose
      were measured both in the seed and in the soaking water during the process (T=30,
      60 and 95 degrees C). A reaction-diffusion model was built for the three
      considered alpha-galactosides both in the seed and in the soaking water, together
      with a model of water transport in the seed. The model reproduced coupled
      reaction-diffusion of alpha-galactosides during the soaking-cooking process with
      a good fit. Produced, diffused and degraded alpha-galactoside fractions were
      identified by performing a mass balance. During soaking at 30 degrees C,
      degradation predominated (maximum found for raffinose degradation rate constant
      of 3.22*10-4s-1) whereas diffusion predominated at higher temperatures (95
      degrees C).

PMID- 29037692
TI  - Evaluation of sn-2 fatty acid composition in commercial infant formulas on the
      Chinese market: A comparative study based on fat source and stage.
AB  - The sn-2 fatty acid composition of 180 commercial infant, follow-on and growing
      up formulas with three fat sources (plant oil, cows' milk and goats' milk) was
      investigated and compared with mature human milk (MHM). Sn-2 fatty acids in
      formulas were mostly dependent on fat source and stage. Compared with MHM, all
      types of formulas contained lower levels of palmitic acid (PA), saturated fatty
      acid and long-chain polyunsaturated fatty acids (LC-PUFA), and higher levels of
      oleic acid (OA), linoleic acid (LA) and alpha-linolenic acid (LNA) at the sn-2
      position. Even some formulas were supplemented with 1,3-dioleoyl-2
      palmitoylglycerol, the proportions of relative PA at the sn-2 position in
      formulas were much lower than that in MHM. Moreover, formulas had higher
      proportions of relative OA, LA and LNA, and lower LC-PUFAs at the sn-2 position.
      This study indicated that there were significant differences in the positional
      distribution of fatty acids between formulas and MHM.

PMID- 29037693
TI  - Conducting polymer modified screen-printed carbon electrode coupled with magnetic
      solid phase microextraction for determination of caffeine.
AB  - In the current study, we introduce magnetic solid phase microextraction coupled
      with electrochemical detection of caffeine. A commercially available disposable
      screen-printed carbon electrodes modified with poly Alizarin Red S are employed
      as electrochemical sensors in the detection stage. However, the suitability of
      magnetic solid phase microextraction for electroanalytical methods such as square
      wave voltammetry has not been declared. With our optimised conditions in hand,
      the system response was linearly proportional to the concentration of caffeine in
      the range of 0.5-20uM with a correlation coefficient of about 0.9987. The
      detection limit of the sensing system was found to be 0.05uM (a signal-to-noise
      ratio of 3). At the end of the study, the suitability of this new procedure for
      the analysis of energy drink, soft drink, and chocolate milk samples was
      demonstrated.

PMID- 29037694
TI  - 1H NMR combined with chemometrics for the rapid detection of adulteration in
      camellia oils.
AB  - Proton nuclear magnetic resonance (1H NMR) and chemometrics were employed to
      detect the adulteration of camellia oil (CAO) with 3 different cheap vegetable
      oils. With the intensity of 15 selected 1H NMR signals as input variables,
      principal component analysis (PCA) showed good group clustering results for pure
      and nonpure CAO, but unsatisfied identification accuracy for the adulterated oil
      types, indicating relatively small difference among those oils. Whereas these
      difference could be revealed by orthogonal projection to latent structures
      discriminant analysis (OPLS-DA), with identification accuracy higher than 90%.
      Partial least squares (PLS) was further applied for the prediction of
      adulteration level in CAO. With less than 6 variables screened out by variable
      importance in the projection (VIP) scores as potential key markers, the developed
      PLS models showed better accuracy. The prediction results for 10 hold-out samples
      also confirmed that this method was accurate and fast for the detection of CAO
      adulteration.

PMID- 29037695
TI  - Monitoring chemical changes during food sterilisation using ultrahigh resolution
      mass spectrometry.
AB  - Sterilised food products undergo chemical changes during processing that
      ultimately determine the product quality. To provide detailed information on the
      chemistry of each stage of a pet-food sterilisation process, a laboratory-scale
      system was developed, which allowed sampling under the high temperatures and
      pressures associated with sterilisation. Products from the laboratory-scale
      system were representative of the factory process. Sample extracts were analysed
      by Fourier Transform-Ion Cyclotron Resonance-Mass Spectrometry (FT-ICR-MS), which
      delivered the molecular formulae and ion intensities of the compounds present.
      Data were examined to determine the coverage of this method, the degree of
      chemical change occurring during pet food thermal processing, and the level of
      identification possible with FT-ICR-MS. Data visualisation and statistical
      analysis identified significant chemical changes in pet food as a result of
      processing, and allowed tentative identification of the compounds involved.
      Insights generated using FT-ICR-MS analysis can be confirmed and further explored
      using conventional, targeted analyses.

PMID- 29037696
TI  - Insights into the multi-scale structure and digestibility of heat-moisture
      treated rice starch.
AB  - The digestibility and structural changes of rice starch induced by heat-moisture
      treatment (HMT) were investigated, and the relationships among the moisture
      content-starch structure-starch digestibility were revealed. HMT could
      simultaneously disorder and reassemble the rice starch molecules across multi
      scale lengths and convert some fractions of rapidly-digestible starch (RDS) into
      slowly-digestible starch (SDS) and resistant starch (RS). In particular, the HMT
      rice starch with less than 30% moisture content showed a higher SDS+RS content
      (25.0%). During HMT, SDS and RS were preferably formed by the degraded starch
      molecules with Mw between 4*105 and 4*106g/mol, single helices and amylose-lipids
      complexes that were formed by degraded starch chains with higher thermal
      stability and crystalline lamellae with greater thicknesses. Thus, our research
      suggests a potential approach using HMT to control the digestion of starch
      products with desired digestibility.

PMID- 29037697
TI  - gamma-PGA and MTGase improve the formation of epsilon-(gamma-glutamyl) lysine
      cross-links within hairtail (Trichiurus haumela) surimi protein.
AB  - The present study investigated the mechanism of epsilon-(gamma-glutamyl) lysine
      cross-links within hairtail (Trichiurus haumela) surimi protein via gamma
      polyglutamic acid (gamma-PGA) and MTGase. The results indicated that the addition
      of MTGase and gamma-PGA markedly improved the gelation properties of hairtail
      surimi protein, including its maximum breaking force and deformation, water
      holding capacity and gel strength. The maximum improvements were achieved by
      adding 0.5units MTGase/g meat paste in combination with 0.06% gamma-PGA. SDS-PAGE
      showed that the band intensity of cross-linked proteins increased, whereas that
      of myosin heavy chain decreased after treatments. Further scanning electron
      microscopy (SEM) analysis showed the formation of a denser gel matrix, which was
      caused by much stronger and more inter- and intra-molecular cross-linking of
      proteins, via MTGase catalysing epsilon-(gamma-glutamyl) lysine cross-links
      formed between lysine residues in the gel protein and glutamic residues in the
      hydrolytic gamma-PGA. The results provide reliable guidance for the improvement
      of hairtail surimi protein gelation properties.

PMID- 29037698
TI  - Rapid and sensitive detection of free fatty acids in edible oils based on
      chemical derivatization coupled with electrospray ionization tandem mass
      spectrometry.
AB  - In this study, a strategy based on chemical derivatization coupled with
      electrospray ionizationtandem quadrupole mass spectrometry (ESI-MS/MS) for rapid
      and sensitive detection of FFAs in edible oils was developed. A derivative
      reagent (N,N-diethyl-1,2-ethanediamine, DEEA) was employed to selectively label
      carboxyl groups of FFAs to form an amino compound with a tertiary amino group.
      The DEEA derivative products could lose a characteristic neutral loss fragment of
      73Da in collision-induced dissociation (CID), which enabled to discriminate and
      analyze the DEEA derived FFAs with neutral loss scan (NLS 73Da)under the positive
      ion mode of mass spectrometry. The assay was linear over the concentration range
      0.5-200nmol/L with satisfactory correlation coefficients (R2>=0.9942), whilst the
      limit of detection and quantitation were 0.1-0.3nmol/L and 0.3-1.0nmol/L,
      respectively. Finally, the established method was applied to determine dynamic
      FFA formation in seven types of edible oils subjected to a microwave heating
      treatment test.

PMID- 29037699
TI  - Determination of hydroxytyrosol produced by winemaking yeasts during alcoholic
      fermentation using a validated UHPLC-HRMS method.
AB  - Hydroxytyrosol (HT) is a phenolic compound of recognized bioactivity that has
      been described in wines but little is known about its origin. This work
      demonstrates that yeast involved in wine making, i.e. Saccharomyces cerevisiae
      strains and the non-Saccharomyces Torulaspora delbrueckii, can synthesise HT, as
      this compound was identified in the intracellular media of three strains by means
      of a developed and validated UHPLC-HRMS method with LOQ and LOD of 0.108 and
      0.035ngmL-1 respectively. Controlled fermentations were performed with different
      varieties of grapes (Corredera, Moscatel, Chardonnay, Palomino fino, Sauvignon
      Blanc, Vijiriega, and Tempranillo) and synthetic must. The Saccharomyces
      cerevisiae strain QA23 was the most efficient producer of HT from tested yeasts.
      On the other hand, the grape variety influences HT wine concentrations.
      Furthermore, the maximum concentration of HT is reached between the fourth and
      sixth day of fermentation. This work reveals that yeasts have a great potential
      for the production of HT.

PMID- 29037700
TI  - Effect of methyl jasmonate on the aroma of Sangiovese grapes and wines.
AB  - Methyl jasmonate (MeJA) was applied in a vineyard on leaves and grape clusters of
      cv Sangiovese to test its ability to stimulate the production of aromas and
      identify the main genes involved in the biosynthetic pathways switched on by the
      elicitor. MeJA application led to a delay in grape technological maturity and a
      significant increase in the concentration of several berry aroma classes (about
      twice the total aroma: from around 3 to 6MUg/g of berry). Of these, monoterpenes
      showed the most significant increase. An analysis of the expression of terpenoid
      biosynthesis genes confirmed that the MeJA application activated the related
      biosynthetic pathway. The expression of all the TPS genes analyzedwas higher in
      samples treated with MeJA. Also the wines produced by microvinification of
      Sangiovese treated and untreated grapes showed a rise in the aroma concentration
      as in berries, with an important impact on longevity and sensorial characters of
      wines.

PMID- 29037701
TI  - Impact of industrial hammer mill rotor speed on extraction efficiency and quality
      of extra virgin olive oil.
AB  - Crushing is a key step during olive oil extraction. Among commercial crushers,
      the hammer mill is the most widely used due to its robustness and high
      throughput. In the present work, the impact of hammer mill rotor speed on
      extraction yield and overall quality of super-high-density Arbosana olive oils
      were assessed in an industrial facility. Our results show that increasing the
      rotor speed from 2400rpm to 3600rpm led to a rise in oil yield of 1.2%, while
      conserving quality parameters. Sensory analysis showed more pungency with
      increased rotation speed, while others attributes were unaffected. Volatile
      compounds showed little variation with the differences in crusher speed; however,
      total phenols content, two relevant secoiridoids, and triterpenoids levels
      increased with rotor speed. Hammer mill rotor speed is a processing variable that
      can be tuned to increase the extraction efficiency and modulate the chemical
      composition of extra virgin olive oil.

PMID- 29037702
TI  - Impact of functional properties and release kinetics on antioxidant activity of
      biopolymer active films and coatings.
AB  - This work deals with the study of the release kinetics of some natural
      antioxidants (ferulic acid, caffeic acid and tyrosol) from chitosan-fish gelatin
      edible films immersed ethanol at 96%, as well as the kinetics of their
      antioxidant activity using the DPPH assay. The aim was to determine how film
      functional properties influence the release kinetic and antioxidant activity. The
      addition of antioxidants to chitosan-fish gelatin matrix decreased the water
      vapour permeability by more than 30%. The tensile strength (TS) increased up to
      50% after the incorporation of antioxidants. Some molecular interactions between
      polymer chains and antioxidants were confirmed by FTIR where spectra displayed a
      shift of the amide-III peak. Films containing caffeic acid or a caffeic-ferulic
      acid mixture exhibited the highest radical scavenging activity, leading to a 90%
      antioxidant activity at equilibrium but the release rate controlled the efficacy
      of the system.

PMID- 29037703
TI  - Effects of moisture and temperature during grain storage on the functional
      properties and isoflavone profile of soy protein concentrate.
AB  - The objective of this study was evaluate the effects of moisture and temperature
      during grain storage on the functional properties and isoflavone profile of soy
      protein concentrate. The protein concentrate was extracted from soybeans on the
      first day of storage and after 12months of storage, at 12 and 15% moisture and at
      temperatures of 11, 18, 25, and 32 degrees C. The protein concentrate obtained
      from grains stored at 32 degrees C showed decreased extraction yield (51.6% with
      15% of moisture) and protein solubility (24.8% with 15% of moisture) with
      increased emulsifying capacity (52.2% with 12% of moisture) and foam formation,
      compared with sample obtained at the start of the storage period. The isoflavone
      profile showed a decrease in the concentrations of glycosylated, malonyl, and
      acetyl isoflavones and a corresponding increase in the concentrations of aglycone
      isoflavones, with the magnitude of these changes increasing with increasing
      storage temperature and moisture content.

PMID- 29037704
TI  - Comparison of the effect of chemical composition of anthocyanin-rich plant
      extracts on colon cancer cell proliferation and their potential mechanism of
      action using in vitro, in silico, and biochemical assays.
AB  - The objective was to compare the anti-proliferative effect of anthocyanin-rich
      plant extracts on human colon cancer cells and determine their mechanism of
      action. Eleven extracts were tested: red (RG) and purple grape, purple sweet
      potato, purple carrot, black and purple bean, black lentil (BL), black peanut,
      sorghum (SH), black rice, and blue wheat. HCT-116 and HT-29 inhibition correlated
      with total phenolics (r=0.87 and 0.77, respectively), delphinidin-3-O-glucoside
      concentration with HT-29 inhibition (r=0.69). The concentration inhibition fifty
      (IC50) for BL, SH, RG on HT-29 and HCT-116 cell proliferation ranged 0.9
      2.0mg/mL. Extracts decreased expression of anti-apoptotic proteins (survivin,
      cIAP-2, XIAP), induced apoptosis, and arrested cells in G1. Anthocyanins
      exhibited tyrosine kinase inhibitory potential in silico and biochemically;
      cyanidin-3-O-glucoside had one of the highest binding affinities with all
      kinases, especially ABL1 (-8.5kcal/mol). Cyanidin-3-O-glucoside and delphinidin-3
      O-glucoside inhibited EGFR (IC50=0.10 and 2.37uM, respectively). Cyanidin-3-O
      glucoside was the most potent anthocyanin on kinase inhibition.

PMID- 29037705
TI  - Stabilization of alpha-lipoic acid by complex formation with octenylsuccinylated
      high amylose starch.
AB  - The thermal and oxidative stability of alpha-lipoic acid (ALA) in aqueous
      dispersions containing beta-cyclodextrin (CD), native high amylose (HA) and
      octenylsuccinylated high amylose (OS) starches (0.1% ALA and 1.0% CD or starch
      solids) were compared. Both native and modified starches increased the stability
      of ALA against thermal degradation and oxidation at higher degrees than CD. The
      OS was more effective in stabilizing ALA than HA. The ALA loss in the dispersions
      occurred mainly in the supernatant, suggesting that the complex formation of ALA
      with amylose played a key role in the stabilization. In an in vitro digestion
      test, the release of ALA from OS dispersion was less than that of HA dispersion,
      indicating that ALA complexed with OS amylose was most stable against digestion.
      The octenylsuccinylated high amylose starch was an effective protecting agent for
      ALA in aqueous media, as well as a delivery carrier for ALA in digestive tract.

PMID- 29037706
TI  - Lutein-enriched emulsion-based delivery systems: Influence of emulsifiers and
      antioxidants on physical and chemical stability.
AB  - The impact of emulsifier type (quillaja saponin, Tween 80, whey protein and
      casein) and antioxidant type (EDTA, ascorbic acid, catechin, alpha tocopherol,
      ascorbic acid palmitate) on the physical and chemical stability of lutein
      fortified emulsions was investigated. Quillaja saponin produced emulsions with
      the best overall stability to droplet aggregation, creaming, and colour fading
      during storage at 45 degrees C for ten days. The impact of antioxidant type on
      the stability of lutein-fortified emulsions prepared using quillaja saponin was
      therefore investigated further. The extent of droplet aggregation and creaming
      was largely independent of antioxidant type. Surprisingly, most of the
      antioxidants promoted lutein degradation. Only ascorbic acid showed some ability
      to inhibit colour fading during storage, although EDTA had some inhibitory
      effects in the early stages of storage. This study suggests that lutein-enriched
      emulsions prepared using quillaja saponin as an emulsifier and ascorbic acid as
      an antioxidant may be the most suitable as delivery systems.

PMID- 29037707
TI  - Predominant yeasts in Chinese traditional sourdough and their influence on aroma
      formation in Chinese steamed bread.
AB  - A total of 105 yeast isolates was obtained from 15 sourdough samples collected
      from different regions in China and subjected to random amplified polymorphic DNA
      (RAPD) analysis. Six species were identified including Pichia membranifaciens,
      which has not previously been reported in Chinese sourdoughs. Different species
      of yeast were used in single-culture fermentation to make Chinese steamed bread
      (CSB). The volatiles of the CSB were captured by solid-phase microextraction
      method, separated and identified by gas chromatography-mass spectrometry. In
      total, 41 volatile compounds were found in all the steamed breads. All CSBs
      showed a similar volatile profile; however, significant differences in the
      quantity of some volatile compounds were seen among the CSB fermented by
      different yeast species. A partial least squares discriminant analysis showed
      that the CSBs could be separated by their characteristic volatile profiles. The
      study suggested that the aromatic properties of CSB are determined by the yeast
      used.

PMID- 29037708
TI  - The effects of edible chitosan-based coatings on flavor quality of raw grass carp
      (Ctenopharyngodon idellus) fillets during refrigerated storage.
AB  - This study investigated the effects of chitosan-based coatings on flavor
      retention of refrigerated grass carp fillets by using various indicators: free
      amino acids (FAA), nucleotides, trimethylamine (TMA), volatile profile, sensory
      quality, and electronic nose analysis. The results indicated that chitosan-based
      coatings contributed to the significant reduction of off-flavor compounds, such
      as TMA, hypoxanthine (Hx) and histidine, and accumulation of inosine
      monophosphate (IMP) and umami-associated FAA. GC-MS analysis showed 23 volatile
      organic compounds, including many C5-C9 aldehydes and alcohols in the fresh
      fillets. The coating treatments, especially chitosan-clove bud essential oil
      composite coatings, sharply reduced the relative content of off-odor volatiles,
      such as hexanal, octanal and 1-octen-3-ol. According to the results of the
      sensory evaluation and electronic nose analyses, chitosan coating combined with
      glycerol monolaurate and clove bud essential oil was a promising method to
      improve the edibility of grass carp fillets by maintaining flavor quality during
      refrigerated storage.

PMID- 29037709
TI  - In vitro digestion and physicochemical characteristics of corn starch mixed with
      amino acid modified by low pressure treatment.
AB  - The digestibility and molecular structure of corn starch mixed with amino acid
      modified by low-pressure treatment (LPT) was investigated. Amino acid induced a
      significant increase in the slowly digestible starch (SDS) and decrease in the
      rapidly digestible starch (RDS) after LPT. The reason is the formation of ester
      bond between the molecular chains of amino acid and starch. Low pressure
      treatment altered greatly the morphology of corn starch mixed with or without
      amino acid. After LPT, less ordered Maltese and more granule fragments were
      observed for starch-amino acid complex. An increase in size distribution was
      obvious after LPT and the size distribution curves provided from a new variety.
      We found that higher enthalpy and relative crystallinity of the starch-amino acid
      complex were associated with a higher SDS content. It can be inferred that LPT
      had a greater impact on the digestion and structural characterization of corn
      starch mixed with amino acids.

PMID- 29037710
TI  - Cooking quality properties and free and bound phenolics content of brown, black,
      and red rice grains stored at different temperatures for six months.
AB  - The changes in cooking quality and phenolic composition of whole black and red
      rice grains stored during six months at different temperatures were evaluated.
      Brown rice with known cooking quality properties and low phenolic levels was used
      for purposes comparison. All rice genotypes were stored at 13% moisture content
      at temperatures of 16, 24, 32, and 40 degrees C. Cooking time, hardness, free and
      bound phenolics, anthocyanins, proanthocyanidins, and free radical scavenging
      capacity were analysed. The traditional rice with brown pericarp exhibited an
      increase in cooking time and free phenolics content, while rice with black
      pericarp exhibited a reduction in cooking time after six months of storage at the
      highest studied temperature of 40 degrees C. There as increases in ferulic acid
      levels occurred as a function of storage temperature. Red pericarp rice grains
      showed decreased antioxidant capacity against ABTS radical for the soluble
      phenolic fraction with increased time and storage temperature.

PMID- 29037711
TI  - Characterization of carotenoids and vitamin E in R. rugosa and R. canina:
      Comparative analysis.
AB  - The hips of Rosa species have gained more attention in recent years due to their
      high contents of antioxidant compounds. This study was designed to compare
      rosehips of the two roses species Rosa rugosa and Rosa canina, including
      different products, on carotenoid contents, including phytoene and phytofluene,
      as well as vitamin E. The investigation allowed the identification and
      quantification of types of (Z)-isomers of lycopene and rubixanthin in both
      rosehips and focused also on isomerisation of both carotenoids. The carotenoid
      identification and quantification were done using HPLC-DAD and LC-MS/MS. The
      statistical analysis revealed significant differences (P<0.05) in carotenoid
      contents and (P<0.001) in vitamin E contents between different rosehips species.
      The HPLC analysis showed that carotenoid contents varied between rosehips
      species. The isomerisation of (all-E)-rubixanthin and (all-E)-lycopene using
      iodine-catalysed photoisomerisation showed that the (5'Z)-isomer gazaniaxanthin
      is the main (Z)-isomer of rubixanthin and the (13Z)-isomer is the main (Z)-isomer
      of lycopene.

PMID- 29037712
TI  - Straightforward analytical method to determine opium alkaloids in poppy seeds and
      bakery products.
AB  - A straightforward method to determine the content of six opium alkaloids
      (morphine, codeine, thebaine, noscapine, papaverine and narceine) in poppy seeds
      and bakery products was developed and validated down to a limit of quantification
      (LOQ) of 0.1mg/kg. The method was based on extraction with
      acetonitrile/water/formic acid, ten-fold dilution and analysis by LC-MS/MS using
      a pH 10 carbonate buffer. The method was applied for the analysis of 41 samples
      collected in 2015 in the Netherlands and Germany. All samples contained morphine
      ranging from 0.2 to 240mg/kg. The levels of codeine and thebaine ranged from
      below LOQ to 348mg/kg and from below LOQ to 106mg/kg, respectively. Sixty percent
      of the samples exceeded the guidance reference value of 4mg/kg of morphine set by
      BfR in Germany, whereas 25% of the samples did not comply with the limits set for
      morphine, codeine, thebaine and noscapine by Hungarian legislation.

PMID- 29037713
TI  - Structural analysis of the alpha-d-glucan produced by the sourdough isolate
      Lactobacillus brevis E25.
AB  - Cereal-associated Lactic Acid Bacteria (LAB) are well known for homopolymeric
      exopolysaccharide (EPS) production. Herein, the structure of an EPS isolated from
      sourdough isolate Lactobacillus brevis E25 was determined. A modified BHI medium
      was used for production of EPS-E25 in order to eliminate potential contaminants.
      Analysis of sugar monomers in EPS revealed that glucose was the only sugar
      present. Structural characterisation of EPS by NMR and methylation analysis
      revealed that E25 produced a highly branched alpha-glucan with (alpha1->3) and
      (alpha1->6) glycosidic linkages, and was similar in structure to a previously
      reported EPS from Lactobacillus reuteri 180. The 1H and 13C NMR data were
      contrasted with newly recorded data for known polysaccharides (alternan,
      commercial dextran) which also contain alpha-(1,3,6)Glc branch points. It was
      found in both E25 EPS and alternan that NMR parameters could be used to
      distinguish glucose residues that had the same substitution pattern but occupied
      different positions in the structure.

PMID- 29037714
TI  - Optimized method for the quantification of pyruvic acid in onions by microplate
      reader and confirmation by high resolution mass spectra.
AB  - The present study describes the rapid microplate method to determine pyruvic acid
      content in different varieties of onions. Onion juice was treated with 2,4
      dinitrophenylhydrazine to obtain hydrazone, which was further treated with
      potassium hydroxide to get stable colored complex. The stability of potassium
      complex was enhanced up to two hours and the structures of hydrazones were
      confirmed by LC-MS for the first time. The developed method was optimized by
      testing different bases, acids with varying concentrations of dinitrophenyl
      hydrazine to get stable color and results were comparable to developed method.
      Repeatability and precision showed <9% relative standard deviation. Moreover,
      sweet onion juice was stored for four weeks at different temperatures for the
      stability; the pyruvate remained stable at all temperatures except at 25 degrees
      C. Thus, the developed method has good potential to determine of pungency in
      large number of onions in a short time using minimal amount of reagents.

PMID- 29037715
TI  - Enhanced CaSO4-induced gelation properties of soy protein isolate emulsion by pre
      aggregation.
AB  - The effects of CaSO4-induced pre-aggregation on the rheological and structural
      properties of soy protein isolate (SPI) emulsion gels were investigated. As the
      Ca2+ concentration during pre-aggregation increased (from 0mM to 7.5mM), the
      elastic modulus of the gels showed substantial increase, indicating stiffer gel
      structures. Large-deformation rheology suggested stronger but more brittle
      networks formed at higher Ca2+ concentration during pre-aggregation. However,
      when the pre-aggregated Ca2+ concentration reached 10mM, the corresponding gel
      became weaker. Water-holding capacity (WHC) of the gels were significantly
      improved via the pre-aggregation process. The differences in rheological
      properties and WHC among the gels were consistent with the variation in their
      microstructures. Pre-aggregation helped to form denser and more uniform
      structures with thicker strands, whereas over aggregation made the gel network
      coarser.

PMID- 29037716
TI  - Chemical composition, nutritional value and antioxidant properties of
      Mediterranean okra genotypes in relation to harvest stage.
AB  - The aim of the present study was to determine the effect of fruit size on
      nutritional value, chemical composition and antioxidant properties of
      Mediterranean okra genotypes. For this purpose, pods from four okra cultivars and
      local landraces commonly cultivated in Greece, as well as pods from four
      commercial cultivars from North America were collected at two sizes (3-5
      and>7cm). Significant differences were observed between the studied genotypes for
      both nutritional value and chemical composition parameters. Small fruit had a
      higher nutritional value, whereas chemical composition differed in a genotype
      dependent manner with most of the studied cultivars showing better results when
      harvested in small size. In conclusion, fruit size has a genotype dependent
      impact on chemical composition and nutritional value of okra pods and the common
      practice of harvesting okra fruit while they still have a small size helps to
      increase nutritional value for most of the studied genotypes.

PMID- 29037717
TI  - Environmentally friendly procedure based on VA-MSPD for the determination of
      booster biocides in fish tissue.
AB  - Booster biocides have been widely applied to ships and other submerged
      structures. These compounds can be released into the marine environment as the
      result of vessel hull leaching and may remain in different environmental
      compartments. This study aimed at introducing an environmentally friendly
      procedure for the extraction of irgarol and diuron from fish samples by vortex
      assisted matrix solid phase dispersion (VA-MSPD) with detection by liquid
      chromatography tandem mass spectrometry. Different types of solid supports and
      solvents were evaluated. The best results were found when 0.5g mussel shell, 0.5g
      sodium sulfate and 5mL ethanol were used. Analytical recoveries ranged from 81 to
      110%, with RSD below 10%, whereas the matrix effect was between -17 and 1% (for
      all samples under study). LOQ values of irgarol and diuron were 5 and 50ngg-1,
      respectively. The method under investigation proved to be a promising alternative
      to controlling contamination of fish by booster biocides, with low consumption of
      biodegradable reagents.

PMID- 29037718
TI  - Co-fermentation of red grapes and white pomace: A natural and economical process
      to modulate hybrid wine composition.
AB  - The impact of co-fermenting white grape pomace (WP) and red grape pomace (RP) on
      the composition of interspecific hybrid wine was studied using the Vitis sp.
      'Frontenac' and 'Vidal'. The proanthocyanidin and anthocyanin content of the
      resulting wines were analysed by HPLC-fluorescence and UPLC-MS/MS, respectively.
      The CIELAB parameters and volatile compounds were analysed using
      spectrophotometry-UV and GC-MS-SPME, respectively. The WP addition increased the
      concentration of monomeric and oligomeric flavan-3-ols, and terpenes in the
      wines. The manipulation of the WP/RP ratio efficiently modulated the anthocyanin
      profile of the wines, resulting in faded red colour, a desirable achievement in
      hybrid red wine, which is usually perceived as too dark. An appropriate ratio
      (30% RP/6% WP) improved the colour stability of the wines without a significant
      impact on wine colour. Addition of WP proved to be a suitable tool to modulate
      the colour, the phenolic and volatile composition of interspecific hybrid wine.

PMID- 29037719
TI  - Low-current & high-frequency electrical stunning increased oxidative stress,
      lipid peroxidation, and gene transcription of the mitogen-activated protein
      kinase/nuclear factor-erythroid 2-related factor 2/antioxidant responsive element
      (MAPK/Nrf2/ARE) signaling pathway in breast muscle of broilers.
AB  - Mechanism of electrical stunning (ES) methods on lipid peroxidation and
      antioxidant protection were studied by determining meat color, serum variables,
      antioxidant-related enzyme activities, gene expressions of mitogen-activated
      protein kinases (MAPKs), nuclear factor-erythroid 2-related factor 2 (Nrf2),
      glutathione S-transferases (GSTs), and superoxide dismutases (SODs). Broilers
      were sacrificed without stunning, or after ES with 65V, 86mA, 1000Hz (E65V) or
      150V, 130mA, 60Hz (E150V). Serum cortisol and uric acid, muscular malondialdehyde
      and mRNA levels of MAPKs, Nrf2, GSTA3, GSTT1 and SOD2 were increased, whereas,
      serum free triiodothyronine, free thyroxine, muscular GST1d activity were
      decreased in E65V compared with E150V. Overall, the serum uric acid and
      transcription of the MAPK/Nrf2/ARE (antioxidant responsive element) signaling
      pathway were elevated, but didn't overcome the oxidative stress stimulated by low
      current & high-frequency ES, leading to aggravated lipid peroxidation at 1d and
      9d postmortem in breast muscle compared with high-current & low-frequency ES.

PMID- 29037720
TI  - Mass spectrometry-based phytochemical screening for hypoglycemic activity of
      Fagioli di Sarconi beans (Phaseolus vulgaris L.).
AB  - The present study deals with the evaluation of antidiabetic activities of Fagioli
      di Sarconi beans (Phaseolus vulgaris), including 21 ecotypes protected by the
      European Union with the mark PGI (i.e., Protected Geographical Indication), and
      cultivated in Basilicata (southern Italy). For this purpose, alpha-glucosidase
      and alpha-amylase assays were assessed; among all bean ecotypes, the tight green
      seed colour of Verdolino extracts exhibited the highest alpha-glucosidase and
      alpha-amylase inhibitory activity with IC50=1.1+/-0.1MUg/ml and IC50=19.3+/
      1.1MUg/ml, respectively. Phytochemical compound screening of all Fagioli di
      Sarconi beans performed by flow injection-electrospray ionization-ultrahigh
      resolution mass spectrometry (uHRMS) and based on the calculation of elemental
      formulas from accurate m/z values, was helpful to annotate specific compounds,
      such as alkaloids, saponins, flavonoids, and terpenoids, which are most likely
      responsible for their biological activity.

PMID- 29037721
TI  - Thermodynamic and kinetic analyses of curcumin and bovine serum albumin binding.
AB  - Bovine serum albumin (BSA)/curcumin binding and dye photodegradation stability
      were evaluated. BSA/curcumin complex showed 1:1 stoichiometry, but the
      thermodynamic binding parameters depended on the technique used and BSA
      conformation. The binding constant was of the order of 105L.mol-1 by fluorescence
      and microcalorimetric, and 103 and 104L.mol-1 by surface plasmon resonance
      (steady-state equilibrium and kinetic experiments, respectively). For native
      BSA/curcumin, fluorescence indicated an enthalpic and entropic driven process
      based on the standard enthalpy change (DeltaH?F=-8.67kJ.mol-1), while
      microcalorimetry showed an entropic driven binding process
      (DeltaH?cal=29.11kJ.mol-1). For the unfolded BSA/curcumin complex, it was found
      thatp DeltaH?F=-16.12kJ.mol-1 and DeltaH?cal=-42.63kJ.mol-1. BSA (mainly native)
      increased the curcumin photodegradation stability. This work proved the
      importance of using different techniques to characterize the protein-ligand
      binding.

PMID- 29037722
TI  - Effect of late harvest and floral origin on honey antibacterial properties and
      quality parameters.
AB  - Honey is a food of high importance due to its nutritional value. The effect of
      late harvest and pollen composition on honey quality and antimicrobial activity
      was studied. Different physicochemical parameters were determined as quality
      indicators. The HMF content, diastase activity, sugar content, antimicrobial
      activity, and hydrogen peroxide content were selected in current work as the
      crucial parameters for evaluation. The results proved that the late harvested
      honey sample showed a vast number of pollens from different blossom periods. The
      hydrogen peroxide content and antimicrobial activity of late harvested honey was
      significantly increased (proved by t-test), whereas the honey seems to be
      affected significantly from weather conditions since the HMF content was also
      increased. The diastase activity was proved to be lower than the respective in
      fresh honey, whereas no difference was observed on the sugar content. Finally,
      the effect of origin and processing in late harvested honey was discussed.

PMID- 29037723
TI  - Thermogravimetric analysis for rapid assessment of moisture diffusivity in
      polydisperse powder and thin film matrices.
AB  - Accurate description of moisture diffusivity is key to precisely understand and
      predict moisture transfer behaviour in a matrix. Unfortunately, measuring
      moisture diffusivity is not trivial, especially at low moisture values and/or
      elevated temperatures. This paper presents a novel experimental procedure to
      accurately measure moisture diffusivity based on thermogravimetric approach. The
      procedure is capable to measure diffusivity even at elevated temperatures (>70
      degrees C) and low moisture values (>1%). Diffusivity was extracted from
      experimental data based on "regular regime approach". The approach was tailored
      to determine diffusivity from thin film and from poly-dispersed powdered samples.
      Subsequently, measured diffusivity was validated by comparing to available
      literature data, showing good agreement. Ability of this approach to accurately
      measure diffusivity at a wider range of temperatures provides better insight on
      temperature dependency of diffusivity. Thus, this approach can be crucial to
      ensure good accuracy of moisture transfer description/prediction especially when
      involving elevated temperatures.

PMID- 29037724
TI  - Nanoemulsion delivery system of tea polyphenols enhanced the bioavailability of
      catechins in rats.
AB  - Tea polyphenols (TP) were emulsified with corn oil and polysorbate 80 by high
      pressure homogenization. The oil in water (O/W) TP nanoemulsion had droplet sizes
      of 99.42+/-1.25nm after preparation. The TP nanoemulsion was stable during
      storage at 4, 25 or 40 degrees C for 20days. An in vitro simulated digestion
      assay showed that the bioaccessibility of (-)-epigallocatechin gallate (EGCG) was
      increased in the nanoemulsion compared to that in aqueous solution, but that the
      bioaccessibilities of (-)-epigallocatechin (EGC), (-)-epicatechin (EC) and (-)
      gallocatechin gallate (GCG) were greatly decreased. Compared with rats fed an
      aqueous TP solution, rats fed the TP nanoemulsion had significantly lower maximum
      plasma concentrations (Cmax) of EGCG and EGC, but the area under the plasma
      concentration-time curve (AUC0-t) was increased. The data show that use of a
      nanoemulsion system to deliver tea polyphenols may enhance the absorption of EGCG
      through controlled release.

PMID- 29037725
TI  - Mineral composition of durum wheat grain and pasta under increasing atmospheric
      CO2 concentrations.
AB  - The concentrations of 10 minerals were investigated in the grain of 12 durum
      wheat genotypes grown under free air CO2 enrichment conditions, and in four of
      their derived pasta samples, using inductively coupled plasma mass spectrometry.
      Compared to ambient CO2 (400ppm; AMB), under elevated CO2 (570ppm; ELE), the
      micro-element and macro-element contents showed strong and significant decreases
      in the grain: Mn, -28.3%; Fe, -26.7%; Zn, -21.9%; Mg, -22.7%; Mo, -40.4%; K, 
      22.4%; and Ca, -19.5%. These variations defined the 12 genotypes as sensitive or
      non-sensitive to ELE. The pasta samples under AMB and ELE showed decreased
      mineral contents compared to the grain. Nevertheless, the contributions of the
      pasta to the recommended daily allowances remained relevant, also for the micro
      elements under ELE conditions (range, from 18% of the recommended daily allowance
      for Zn, to 70% for Mn and Mo).

PMID- 29037726
TI  - gamma-Fe2O3 magnetic nanoparticle functionalized with carboxylated multi walled
      carbon nanotube for magnetic solid phase extractions and determinations of Sudan
      dyes and Para Red in food samples.
AB  - Hybrid nanostructures composed of gamma-Fe2O3 (maghemite) and carboxylated-multi
      walled carbon nanotube (cMWCNT) were used for the magnetic solid phase
      extractions and determination of Sudan I, II, III, IV, Para Red, Sudan Black B
      and Sudan Red 7B in chili products. High performance liquid chromatography (HPLC)
      was employed for the measurements. Limit of quantification (LOQ) values were
      found in the range 0.44-2.82ngmL-1 for analytes. The best extraction parameters
      were determined as pH 8.0, 40mg of magnetic nanoparticle, 4.0min of contact time,
      0.3mL desorption by acetonitrile. The samples were dissolved in acetone
      dichloromethane-methanol (3:2:1, v/v/v) and diluted with acetonitrile-methanol
      (v/v; 80:20) before the method was applied. Concentrations of Sudan dyes and Para
      Red were determined in four samples of chili powder from less than LOQ to 31.21+/
      1.6ngg-1, two samples of chili tomato sauces (lower than LOQ) and two samples of
      ketchup (lower than LOQ).

PMID- 29037727
TI  - Modifications of cell wall pectin in chilling-injured 'Friar' plum fruit
      subjected to intermediate storage temperatures.
AB  - 'Friar' plum (Prunus salicina Lindl.) fruit were stored at low (0 degrees C),
      intermediate (5 and 15 degrees C) and ambient temperature (25 degrees C). Flesh
      translucency was evidenced as the main chilling injury (CI) symptom and the CI
      developed rapidly at 5 and 15 degrees C but suppressed at 0 degrees C.
      Modifications of cell wall pectin in 'Friar' plums were investigated during
      storage. Sodium carbonate-soluble pectin (SSP) was found to be predominant in the
      fruit but it decreased more rapidly at 5 and 15 degrees C than 0 degrees C.
      Nevertheless, SSP possessed abundant galactose, arabinose and rhamnose at 5 and
      15 degrees C. Nanostructural observations indicated that the detachment and
      degradation of linear backbone chains in SSP molecules were enhanced at 5 and 15
      degrees C. Therefore, the development of CI of 'Friar' plums at intermediate
      temperatures was associated with the modifications of SSP in the cell wall pectin
      of the fruit subjected to chilling stress.

PMID- 29037728
TI  - Structural polymeric features that contribute to in vitro immunostimulatory
      activity of instant coffee.
AB  - An instant coffee fraction, rich in arabinogalactans, obtained by
      ultrafiltration, using 1 and 5kDa membranes, has previously shown in vitro
      stimulatory activity on BALB/c mice spleen B lymphocytes. The compounds inducing
      lymphocytic activation were shown to elute, mainly near the void volume by size
      exclusion chromatography, using Bio-Gel P6 (1-6kDa). Treatment of the compounds
      with chymotrypsin, a digestive protease, did not affect the induced B lymphocyte
      activation. On the contrary, hydrolysis with an alpha-l-arabinofuranosidase,
      removing single terminally-linked arabinose residues, decreased the extent of B
      cell activation. The immunostimulatory activity of these compounds was also
      observed by in vitro experiments, using bone marrow-derived macrophages and
      dendritic cells as responders. Altogether, these results show the relevance of
      single arabinose residues, present at the non-reducing end of polymeric
      compounds, to the coffee stimulatory activity in cells mediating innate and
      acquired immunity.

PMID- 29037729
TI  - Evaluation of folate-binding proteins and stability of folates in plant foliages.
AB  - The present study reports the presence of folate binding proteins (FBPs) in the
      plants, coriander and Arabidopsis, and their contributions toward folate
      enhancement. After observing that salicylic acid (SA) enhanced the accumulation
      of folates in coriander, a study was conducted in Arabidopsis, where twofold
      increase in folates occurred in foliage upon SA treatment. For obtaining insights
      into genes involved in SA-induced folate accumulation, microarray data of
      responsive genes in Arabidopsis were screened. Based on the expression profiles,
      19 genes were further analysed by qPCR. The results revealed that folate
      biosynthetic genes were largely down-regulated, whereas a gene of a putative
      folate-binding protein (FPB) was up-regulated, which correlated with a
      significant increase of FPBs in foliage. This new information on a plant FBP
      appears useful for metabolic engineering of a wide range of crops to enhance the
      content and stability of the folates during post-harvest storage.

PMID- 29037731
TI  - Sequential extraction of gel-forming proteins, collagen and collagen hydrolysate
      from gutted silver carp (Hypophthalmichthys molitrix), a biorefinery approach.
AB  - Collagen and collagen hydrolysate (CH) was recovered from the bone and skin
      containing sediment residue emerging during pH-shift-based protein isolation from
      silver carp. Hydrolysis resulted in higher yield (15.1-15.4%) compared to
      collagen isolation by acid or pepsin (3.1-5.9%) (p<0.05). Isolated collagens were
      characterized as type I and maintained their triple-helical structure, confirmed
      by SDS-PAGE and FTIR. Pepsin-hydrolysis and sequential hydrolysis by pepsin and
      trypsin hydrolyzed all heavy molecular weight chains of collagen but sequential
      hydrolysis yielded higher degree of hydrolysis. When CH was added to a silver
      carp protein isolate prior to gelation, the gel behavior was dependent on
      molecular weight of the added CH. More hydrolyzed collagen emerging from
      sequential hydrolysis improved water holding capacity of the gel while reducing
      its breaking force. Thus, residue from pH-shift processing of fish can be used
      for isolation of high quality collagen/CH and provides a promising basis for a
      multiple-product fish biorefinery.

PMID- 29037730
TI  - Citrus fruits freshness assessment using Raman spectroscopy.
AB  - The freshness of citrus fruits commonly available in the market was non
      destructively assessed by Raman spectroscopy. Intact clementine, mandarin and
      tangerine species were characterised concerning their carotenoids skin Raman
      signalling in a time course from the moment they were acquired as fresh stock,
      supplying the market, to the physical degradation, when they were no longer
      attractive to consumers. The freshness was found to strongly correlate to the
      peel Raman signal collected from the same area of the intact fruits in a time
      course of a maximum of 20days. We have shown that the intensity of the carotenoid
      Raman signal is indeed a good indicator of fruit freshness and introduced a Raman
      coefficient of freshness (CFresh), whose time course is linearly decreasing, with
      different slope for different citrus groups. Additionally, we demonstrated that
      the freshness assessment could be achieved using a portable Raman instrument. The
      results could have a strong impact for consumer satisfaction and the food
      industry.

PMID- 29037732
TI  - Arabinoxylanase from glycoside hydrolase family 5 is a selective enzyme for
      production of specific arabinoxylooligosaccharides.
AB  - An arabinose specific xylanase from glycoside hydrolase family 5 (GH5) was used
      to hydrolyse wheat and rye arabinoxylan, and the product profile showed that it
      produced arabinose substituted oligosaccharides (AXOS) having 2-10 xylose
      residues in the main chain but no unsubstituted xylooligosaccharides (XOS).
      Molecular modelling showed that the active site has an open structure and that
      the hydroxyl groups of all xylose residues in the active site are solvent
      exposed, indicating that arabinose substituents can be accommodated in the
      glycone as well as the aglycone subsites. The arabinoxylan hydrolysates obtained
      with the GH5 enzyme stimulated growth of Bifidobacterium adolescentis but not of
      Lactobacillus brevis. This arabinoxylanase is thus a good tool for the production
      of selective prebiotics.

PMID- 29037733
TI  - Continuous exposure to ethylene in the storage environment adversely affects
      'Afourer' mandarin fruit quality.
AB  - 'Afourer' mandarins were stored in air containing ethylene at 0.001, 0.01, 0.1,
      and 1MULL-1 at 20, 10, 5 and 0 degrees C and changes in a range of external and
      internal quality parameters were examined for up to 10weeks in storage. At all
      storage temperatures, reducing ethylene concentration in the storage environment
      decreased the rate of respiration, visible deterioration of the calyx region,
      ethanol accumulation in the juice, loss of eating quality, and at chilling
      temperatures reduced rind pitting. The quality attributes limiting mandarin
      storage life differed between the different storage temperatures but retention of
      mandarin quality was always optimised by maintaining the lowest possible ethylene
      atmosphere around fruit. Thus, the primary target should be to ensure the
      ethylene levels are <=0.01MULL-1, as loss of quality was accelerated above this
      concentration.

PMID- 29037734
TI  - Reducing the negative sensory impact of volatile phenols in red wine with
      different chitosans: Effect of structure on efficiency.
AB  - "Brett character" is a negative sensory attribute acquired by red wines when
      contaminating Dekkera/Brettanomyces yeasts produce 4-ethylphenol and 4
      ethylguaiacol, known as volatile phenols (VPs), from cinnamic acid precursors. In
      this study, chitins and chitosans with different structural features, namely
      deacetylation degree (5-91%) and molecular weight (24-466kDa) were used for the
      reduction of this sensory defect. Chitins and chitosans decreased 7-26% of the
      headspace abundance of VPs without changing their amounts in wines. The
      efficiency of reduction increased with the deacetylation degree and applied dose.
      Reduction of headspace abundance of VPs by chitosans enabled significant
      decreases in the negative phenolic and bitterness attributes and increased
      positive fruity and floral attributes. Results show that chitosan with high
      deacetylation degrees, including fungal chitosan, which is already approved for
      use in wines, is an efficient approach for reducing the negative sensory impact
      of VPs in red wines.

PMID- 29037735
TI  - l-Theanine: An astounding sui generis integrant in tea.
AB  - l-theanine (l-Th), a non-protein amino acid present in tea, is a valuable
      nutraceutical product with unique health benefits and used as an additive in food
      industry. l-Th enhances the umami taste but its use is limited due to its
      inadequate production. Different extraction approaches from tea shoots, chemical
      synthesis to microbial transformation have been tried to meet its demand. In
      vitro, in vivo as well as clinical studies have shown its positive effect in
      regulating CNS disorders. l-Th has become choice ingredient in CNS active
      products due to its anti-stress and neuroprotective role in dementias
      particularly in retrogression of Alzheimer's. l-Th biochemically modulates
      various anti-neoplastic agents by increasing their bioavailability in tumour
      cells. The review, is an effort to condense the recent research on l-Th
      highlighting its biological resource, plausible role in tea plant, production
      approaches, its physiological role on human health and future prospects.

PMID- 29037736
TI  - DNA barcoding based identification of Hippophae species and authentication of
      commercial products by high resolution melting analysis.
AB  - Sea buckthorn (Hippophae), an ancient crop with modern virtues, is increasingly
      consumed in source of foods and nutraceuticals. The growing demand leads to the
      adulteration of commercial sea buckthorn products, which is a common form of food
      fraud. Herein, a high resolution melting assay, targeting a DNA barcoding region
      of the internal transcribed spacer 2 (ITS2) (Bar-HRM) was developed to identify
      the seven native Chinese Hippophae species, and to authenticate commercial sea
      buckthorn products. Melting data from the HRM assay demonstrated that all
      Hippophae species could be clearly distinguished. Then, application to commercial
      sea buckthorn products indicated the existence of adulterants or contamination,
      further confirmed using Sanger sequencing results for PCR products from HRM. The
      Bar-HRM technique proposed in this work could provide a method for regulatory
      agencies, promoting consumers trust, and raise the quality and safety of sea
      buckthorn products.

PMID- 29037737
TI  - The impact of disulfide bond dynamics in wheat gluten protein on the development
      of fermented pastry crumb.
AB  - Gluten proteins functionality during pastry production was examined by including
      redox agents in the ingredient bill. Addition of reducing and oxidizing agents
      respectively increased and decreased dough height during fermentation. The
      presence of large gas bubbles in the samples with oxidizing agents may have
      caused a 'stacking'-effect and a more effective dough lift. During baking, the
      level of extractable proteins decreased to comparable values for all samples,
      except when potassium iodate (KIO3) was used in the recipe. As a result of its
      use, a lower level of gliadin was incorporated into the gluten polymer and dough
      layers tended to 'slide' apart during baking, thereby causing collapse. Most
      likely, KIO3 caused glutenin oxidation within each individual dough layer to such
      extent during the dough stage that insufficient thiol groups were available for
      forming dough layer interconnections during baking, after margarine melting.
      Furthermore, addition of redox agents impacted the product's crumb structure.

PMID- 29037738
TI  - Peptides derived from in vitro gastrointestinal digestion of germinated soybean
      proteins inhibit human colon cancer cells proliferation and inflammation.
AB  - The aim was to investigate the potential of germinated soybean proteins asa
      source of peptides with anticancer and anti-inflammatory activities produced
      after simulated gastrointestinal digestion. Protein concentrate from germinated
      soybean was hydrolysed with pepsin/pancreatin and fractionated by
      ultrafiltration. Whole digest and fractions>10, 5-10, and<5kDa caused
      cytotoxicity to Caco-2, HT-29, HCT-116 human colon cancer cells, and reduced
      inflammatory response caused by lipopolysaccharide in macrophages RAW 264.7.
      Antiproliferative and anti-inflammatory effects were generally higher in 5-10kDa
      fractions. This fraction was further purified by semi-preparative chromatography
      and characterised by HPLC-MS/MS. The most potent fraction was mainly composed of
      beta-conglycinin and glycinin fragments rich in glutamine. This is the first
      report on the anti-cancer and anti-inflammatory effects of newly isolated and
      identified peptides from germinated soybean released during gastrointestinal
      digestion. These findings highlight the potential of germination as a process to
      obtain functional foods or nutraceuticals for colon cancer prevention.

PMID- 29037739
TI  - Targeted regulation of hygroscopicity of soybean antioxidant pentapeptide powder
      by zinc ions binding to the moisture absorption sites.
AB  - In the present study, a targeted regulation of hygroscopicity of soybean
      antioxidant pentapeptide (SAP) powder was explored by zinc ions binding to its
      moisture absorption sites. Scanning electron microscopy, X-ray diffraction
      analysis, Fourier transform infrared spectroscopy and an energy-dispersive X-ray
      spectroscope were used to confirm the formation of the SAP-zinc complex. The
      results showed that morphology of SAP-zinc complex belonged to crystalline
      nanoparticles. The moisture sorption/desorption kinetics of the SAP-zinc complex
      changed compared to that of the SAP. In particular, the moisture sorption
      capacity of the SAP decreased and the distribution of adsorbed water changed
      after zinc chelation. Based on the binding of zinc ions to the moisture
      absorption sites, the hygroscopicity of SAP powder could be target regulated.
      Thus, this study could provide a new method to regulate the hygroscopicity of
      peptide powder.

PMID- 29037740
TI  - Antioxidant activity of rosemary essential oil fractions obtained by molecular
      distillation and their effect on oxidative stability of sunflower oil.
AB  - The objective of this study was to evaluate the antioxidant activity of rosemary
      essential oil fractions obtained by molecular distillation (MD) and investigate
      their effect on the oxidative stability of sunflower oil. MD fractions were
      prepared in a series of low-pressure stages where rosemary essential oil was the
      first feed. Subsequently, a distillate (D1) and residue (R1) were obtained and
      the residue fraction from the previous stage used as the feed for the next. The
      residue fractions had the largest capacity to capture free radicals, and the
      lowest peroxide values, conjugated dienes and conjugated trienes. The antioxidant
      activity of the fractions was due to oxygenated monoterpenes, specifically alpha
      terpineol and cis-sabinene hydrate. Oxidative stability results showed the
      residues (R1 and R4) and butylated hydroxytoluene had greater antioxidant
      activity than either the distillate fractions or original rosemary essential oil.
      The residue fractions obtained by short path MD of rosemary essential oil could
      be used as a natural antioxidants by the food industry.

PMID- 29037741
TI  - Influence of emulsion interfacial membrane characteristics on Ostwald ripening in
      a model emulsion.
AB  - Ostwald ripening is a major destabilization mechanism for emulsions containing
      flavor oils with relatively high water solubilities. Emulsions with different oil
      phase compositions were prepared that were stabilized by polyoxyethylene alkyl
      ether-type emulsifiers with differently sized hydrophilic and hydrophobic groups.
      Emulsions prepared using only orange oil were highly unstable to Ostwlad ripening
      during storage. When emulsifier concentration was increased, Ostawald ripening in
      emulsions containing emulsifiers with small hydrophilic groups was inhibited,
      while size increment of droplets in emulsions containing emulsifiers with large
      hydrophilic groups was not. Droplet enlargement was effectively inhibited by
      incorporating corn oil into the oil phase prior to homogenization. However, the
      concentration of corn oil required to inhibit Ostwald ripening varied depending
      on the structural characteristics and concentrations of the emulsifiers present.
      These results could have important implications for the selection of emulsifiers
      to improve the physical stability of orange oil emulsions for use in the food and
      beverage industries.

PMID- 29037742
TI  - Augmentation of chemical and organoleptic properties in Syzygium cumini wine by
      incorporation of grape seeds during vinification.
AB  - The role of grape seed tannins on improving organoleptic properties and its
      involvement in color stabilization in red wine are well established. The addition
      of grape seeds as the source of condensed tannins in fruit wine may provide a
      solution for its color instability and improvement of sensory attributes. Syzgium
      cumini is traditionally known for its therapeutic properties. In the current
      study, the influence of yeasts and grape seed addition during fermentation on the
      chromatic, phenolic and sensory attributes of the wine was accessed. Grape seed
      addition improved the color characteristics of wine and increased overall
      phenolic composition. Analysis by HPLC revealed 6 major anthocyanins, among which
      3, 5-diglucoside form of delphidin and petunidin was found to be the major
      components. Cluster and PLSR analysis explained the impact of seed addition on
      the yeasts, as well as on the perception of panelists, with bitterness and
      astringency as the dominating attributes.

PMID- 29037743
TI  - The effect of platelet-rich fibrin on autologous osteochondral transplantation:
      An in vivo porcine model.
AB  - BACKGROUND: This work aimed to evaluate the efficacy of cartilage transplantation
      to the medial femoral condyle+/-platelet-rich fibrin (PRF) augmentation in a
      porcine model. The hypothesis of the study was that PRF may act as a bioactive
      cell scaffold to fill defects and enhance cartilage regeneration. METHODS: Thirty
      two knees of 16 miniature pigs were randomly assigned to four groups. The
      critical-size osteochondral defects (8x5mm) in femoral condyle of both knees were
      treated with one of the following: group 1-untreated controls; group 2-cartilage
      fragments alone; group 3-PRF alone; group 4-PRFT+cartilage fragments. After
      completion of the surgical implantation, the periosteal patch harvested from the
      proximal tibia was sutured onto the cartilage of the medial condyle to cover the
      implanted defects. Animals were sacrificed at six months after treatment. The
      regenerated cartilages were assessed by gross inspection and histological
      examination. RESULTS: The best results were obtained with the repair tissue being
      hyaline-like cartilage (group 4). The grading score of histological evaluation
      demonstrated that group 4 had better matrix, cell distribution and cartilage
      mineralization than group 2 and group 3. PRF showed a positive effect on the
      cartilage repair; the procedure was more effective when PRF was combined with
      autologous chondrocytes. CONCLUSIONS: This approach may provide a successfully
      employed technique to target cartilage defects in vivo. Larger groups and longer
      periods of study may provide more definitive and meaningful support for using
      this therapeutic approach as a new way of cartilage regeneration.

PMID- 29037744
TI  - Intoxication from the novel synthetic cannabinoids AB-PINACA and ADB-PINACA: A
      case series and review of the literature.
AB  - Synthetic cannabinoids (SC), are a novel class of designer drugs which emerged as
      a drug of abuse in the late 2000's. We report a case series of 6 patients who may
      have smoked a synthetic cannabinoid product in a remote wilderness setting. They
      presented with varying degrees of altered mental status, agitation, and seizures.
      Two were confirmed to have AB-PINACA, ADB-PINACA and their respective pentanoic
      acid metabolites in biological specimens via liquid chromatography time-of-flight
      mass spectrometry (LC-TOF/MS). Both compounds had DEA Schedule I classification
      at the time of case presentation, and 22 SCs are currently temporary or permanent
      DEA Schedule I. More than 150 SCs are known to date, and new compounds are
      appearing at a rapid rate on darknet and surface web e-commerce websites,
      marketed as "research chemicals" or "legal highs." The scale and rapidity of SC
      evolution make legal control and analytical detection difficult. Nontargeted
      testing with liquid chromatography high resolution mass spectrometry (LC-HRMS),
      examining both parent compounds and metabolites, is the ideal method for novel SC
      identification and confirmation. Due to full agonism at the cannabinoid receptors
      CB1 and CB2, clinical effects are more severe than marijuana, which is a partial
      cannabinoid receptor agonist. They include agitated delirium, lethargy and coma,
      seizures, tachycardia, hypertension, and hallucinations, among other findings.
      Treatment is primarily symptomatic and aimed at airway protection and control of
      agitation and seizures. SCs do not appear to be abating anytime soon and require
      the cooperation of law enforcement, analytical scientists, and clinicians to
      adequately control. This article is part of the Special Issue entitled 'Designer
      Drugs and Legal Highs.'

PMID- 29037745
TI  - Genetics update: Monogenetics, polygene disorders and the quest for modifying
      genes.
AB  - The genetic channelopathies are a broad collection of diseases. Many ion channel
      genes demonstrate wide phenotypic pleiotropy, but nonetheless concerted efforts
      have been made to characterise genotype-phenotype relationships. In this review
      we give an overview of the factors that influence genotype-phenotype
      relationships across this group of diseases as a whole, using specific individual
      channelopathies as examples. We suggest reasons for the limitations observed in
      these relationships. We discuss the role of ion channel variation in polygenic
      disease and highlight research that has contributed to unravelling the complex
      aetiological nature of these conditions. We focus specifically on the quest for
      modifying genes in inherited channelopathies, using the voltage-gated sodium
      channels as an example. Epilepsy related to genetic channelopathy is one area in
      which precision medicine is showing promise. We will discuss the successes and
      limitations of precision medicine in these conditions. This article is part of
      the Special Issue entitled 'Channelopathies.'

PMID- 29037746
TI  - Cystic parathyroid as a cause of hypercalcemia.

PMID- 29037747
TI  - Advancement Flap Technique for Anal Fistula in Patients With Crohn's Disease: A
      Systematic Review of the Literature.
AB  - INTRODUCTION: Treatment for anal fistulas in patients with Crohn's disease is
      still challenging, even for the expert surgeon. The advancement flap technique is
      characterized by the preservation of the anal sphincter complex. METHODS: A
      systematic review of the literature, selecting series of patients affected by
      Crohn's disease and anal fistulas and treated using advancement flap technique
      was performed. Patients followed during at least 6 months have been included.
      RESULTS: From 128 initial studies, 11 studies were selected, including overall
      135 patients. Those studies show low- level evidence. Results in a series with
      follow-up from 8,4 to 82 months, stated a clinical success of 66% and recurrence
      rate around 30%. However there was an evident heterogeneity of results.
      CONCLUSION: The review concludes that the advancement flap technique to treat
      anal fistulas in patients with Crohn's disease is an adequate alternative. New
      studies are necessary to provide higher-level evidence.

PMID- 29037748
TI  - Oncological results of the educational Rectal Cancer Project in Spain 10 years
      after its implementation.
AB  - INTRODUCTION: The objective of this observational, prospective, multicenter and
      multilevel study was to evaluate the oncological outcomes (local recurrence,
      metastasis and overall survival) of the Rectal Cancer Project of the Spanish
      Association of Surgeons (AEC) 10 years after its initiation, comparing the
      results with Scandinavian registries. METHODS: The AEC teaching project database
      includes 17,620 patients to date, of which 4,508 were operated on with a
      potentially curative resection between March 2006 and December 2010. All of them
      come from the first 59 hospitals included in the project, and therefore followed
      for at least 5 years, and are the subject of the present study. RESULTS: The
      cumulative incidence of local recurrence was 7.3 (95% CI: 8.2-6.5), metastasis
      21.0 (CI 95%: 22.4-19.7) and overall survival 72.3 (CI 95%: 80.3-77.6). The
      multilevel regression analysis with the hospital variable as a random effect,
      showed a significant variation among the hospitals for the cancer outcome
      variables: general survival, local recurrence and metastasis (delta2=0.053).
      CONCLUSIONS: This study indicates that the results observed in the AEC' Rectal
      Cancer Project are inferior than those observed in the Scandinavian registries
      that we tried to emulate and that this is attributable to the variability of
      practice in some centers.

PMID- 29037749
TI  - Psychopathological features in Noonan syndrome.
AB  - INTRODUCTION: Noonan syndrome (NS) is an autosomal dominant disorder
      characterized by short stature, skeletal and haematological/lymphatic defects,
      distinctive facies, cryptorchidism, and a wide spectrum of congenital heart
      defects. Recurrent features also include variable cognitive deficits and
      behavioural problems. Recent research has been focused on the assessment of
      prevalence, age of onset and characterization of psychiatric features in this
      disorder. Herein, we evaluated the prevalence of attention deficit and
      hyperactivity disorder (ADHD), anxiety and depressive symptoms and syndromes in a
      cohort of individuals with clinical and molecular diagnosis of NS. METHODS: The
      Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children
      Present and Lifetime version (K-SADS PL) has been used for the assessment of
      psychiatric disorders according to Diagnostic and Statistical Manual of Mental
      Disorders (DSM-IV). Multidimensional Anxiety Scale for Children (MASC) and the
      Children's Depression Inventory (CDI) have been assessed for the evaluation of
      anxiety and depressive symptoms and syndromes, whereas Conners Teacher and Parent
      Rating Scales-long version (CRS-R) have been used to evaluate ADHD. RESULTS: The
      study included 27 individuals (67% males) with an average age of 10.4 years
      (range 6-18 years) receiving molecular diagnosis of NS or a clinically related
      condition, evaluated and treated at the Neuropsychiatric Unit of Children's
      Hospital Bambino Gesu and at the Center for Rare Diseases of Fondazione
      Policlinico Universitario Agostino Gemelli, in Rome. Twenty individuals showed
      mutations in PTPN11, five in SOS1 and two in SHOC2. The mean IQ was 94 (Standard
      Deviation = 17, min = 56, max = 130). Seventy percent of the individuals (n = 19;
      95% Confidence Interval = 52-85%) showed ADHD features, with six individuals
      reaching DSM-IV-TR criteria for ADHD disorder, and thirteen showing subsyndromal
      traits. Symptoms or syndrome of anxiety were present in 37% of the cohort (n =
      10; 95% Confidence Interval = 19-56%), with two individuals showing anxiety
      disorder and eight cases exhibiting subsyndromal traits. CONCLUSION: Our results
      show individuals with NS do present a very high risk to develop psychiatric
      disorders or symptoms during paediatric age. Based on these findings, preschool
      assessment of inattentive, hyperactivity/impulsivity and anxiety/depressive
      symptoms is recommended in order to plan a personalized treatment for
      psychological/psychiatric issues in affected individuals. Dedicated prospective
      studies are required to confirm the present data and better characterize the
      psychopathological profile in NS.

PMID- 29037750
TI  - Environmental toxicology and omics: A question of sex.
AB  - : Molecular initiating events and downstream transcriptional/proteomic responses
      provide valuable information for adverse outcome pathways, which can be used
      predict the effects of chemicals on physiological systems. There has been a
      paucity of research that addresses sex-specific expression profiling in
      toxicology and due to cost, time, and logistical considerations, sex as a
      variable has not been widely considered. In response to this deficiency, federal
      agencies in the United States, Canada, and Europe have highlighted the importance
      of including sex as a variable in scientific investigations. Using case studies
      from both aquatic and mammalian toxicology, we report that there can be less than
      ~20-25% consensus in how the transcriptome and proteome of each sex responds to
      chemicals. Chemicals that have been shown to elicit sex-specific responses in the
      transcriptome or proteome include pharmaceuticals, anti-fouling agents,
      anticorrosive agents, and fungicides, among others. Sex-specific responses in the
      transcriptome and proteome are not isolated to whole animals, as investigations
      demonstrate that primary cell cultures isolated from each sex responds
      differently to toxicants. This signifies that sex is important, even in cell
      lines. Sex has significant implications for predictive toxicology, and both male
      and female data are required to improve robustness of adverse outcome pathways.
      BIOLOGICAL SIGNIFICANCE: Clinical toxicology recognizes that sex is an important
      variable, as pharmacokinetics (ADME; absorption, distribution, metabolism, and
      excretion) can differ between females and males. However, few studies in
      toxicology have explored the implication of sex in relation to the transcriptome
      and proteome of whole organisms. High-throughput molecular approaches are
      becoming more frequently applied in toxicity screens (e.g. pre-clinical
      experiments, fish embryos, cell lines, synthetic tissues) and such data are
      expected to build upon reporter-based cell assays (e.g. receptor activation,
      enzyme inhibition) used in toxicant screening programs (i.e. Tox21, ToxCast,
      REACH). Thus, computational models can more accurately predict the diversity of
      adverse effects that can occur from chemical exposure within the biological
      system. Our studies and those synthesized from the literature suggest that the
      transcriptome and proteome of females and males respond quite differently to
      chemicals. This has significant implications for predicting adverse effects in
      one sex when using molecular data generated in the other sex. While molecular
      initiating events are not expected to differ dramatically between females and
      males (i.e. an estrogen binds estrogen receptors in both sexes), it is important
      to acknowledge that the downstream transcriptomic and proteomic responses can
      differ based upon the presence/absence of co-regulators and inherent sex-specific
      variability in regulation of transcriptional and translational machinery.
      Transcriptomic and proteomic studies also reveal that cell processes affected by
      chemicals can differ due to sex, and this can undoubtedly lead to sex-specific
      physiological responses.

PMID- 29037751
TI  - Discrimination and Risk for Suicide in Later Life.

PMID- 29037752
TI  - Caring for Nursing Home Residents with Agitation Continues to be Very
      Challenging.

PMID- 29037753
TI  - Cancer-Related Cognitive Impairment: Considering Risk Factors, Approaching
      Assessment, and Contemplating Treatment.

PMID- 29037754
TI  - Antiviral effects of Lactobacillus crispatus against HSV-2 in mammalian cell
      lines.
AB  - BACKGROUND: Herpes simplex virus type 2 (HSV-2) infectious disease is one of the
      most common viral sexually transmitted diseases. As regards, vaginal lactobacilli
      play an important role in protecting host against the urogenital pathogens; here
      we assessed the potential antiviral activity of Lactobacillus crispatus against
      HSV-2 infection in vitro. METHODS: Both Vero and HeLa cell lines were treated by
      L. crispatus before, during and after HSV-2 infection. The pre-incubation assay
      was also performed for the evaluating of virus adsorption by L. crispatus. Virus
      titer reduction in each stage was determined by a plaque reduction assay.
      RESULTS: L. crispatus significantly decreased the infectivity of the HSV-2 in
      initial steps on both cell lines; however, no significant inhibition was
      ascertained during adsorption and multiplication process. The lactobacilli adhere
      on Vero cells two-fold stronger than HeLa and subsequently protect the Vero cells
      nearly 2.5 fold higher than HeLa cell against the virion. Co-incubation of HSV-2
      with bacterial cells prior to virus inoculation significantly decreased the virus
      titer. CONCLUSION: L. crispatus appears to inhibit the entry of the virus into
      cells by trapping HSV-2 particles. In addition, formation of L. crispatus
      microcolonies in the cell surface could block HSV-2 receptors and prevent viral
      entry to cells in initial infection steps.

PMID- 29037755
TI  - Biochemical identification of residues that discriminate between 3,4
      dihydroxyphenylalanine decarboxylase and 3,4-dihydroxyphenylacetaldehyde synthase
      mediated reactions.
AB  - In available insect genomes, there are several L-3,4-dihydroxyphenylalanine (L
      dopa) decarboxylase (DDC)-like or aromatic amino acid decarboxylase (AAAD)
      sequences. This contrasts to those of mammals whose genomes contain only one DDC.
      Our previous experiments established that two DDC-like proteins from Drosophila
      actually mediate a complicated decarboxylation-oxidative deamination process of
      dopa in the presence of oxygen, leading to the formation of 3,4
      dihydroxyphenylacetaldehyde (DHPA), CO2, NH3, and H2O2. This contrasts to the
      typical DDC-catalyzed reaction, which produces CO2 and dopamine. These DDC-like
      proteins were arbitrarily named DHPA synthases based on their critical role in
      insect soft cuticle formation. Establishment of reactions catalyzed by these AAAD
      like proteins solved a puzzle that perplexed researchers for years, but to tell a
      true DHPA synthase from a DDC in the insect AAAD family remains problematic due
      to high sequence similarity. In this study, we performed extensive structural and
      biochemical comparisons between DHPA synthase and DDC. These comparisons
      identified several target residues potentially dictating DDC-catalyzed and DHPA
      synthase-catalyzed reactions, respectively. Comparison of DHPA synthase homology
      models with crystal structures of typical DDC proteins, particularly residues in
      the active sites, provided further insights for the roles these identified target
      residues play. Subsequent site-directed mutagenesis of the tentative target
      residues and activity evaluations of their corresponding mutants determined that
      active site His192 and Asn192 are essential signature residues for DDC- and DHPA
      synthase-catalyzed reactions, respectively. Oxygen is required in DHPA synthase
      mediated process and this oxidizing agent is reduced to H2O2 in the process.
      Biochemical assessment established that H2O2, formed in DHPA synthase-mediated
      process, can be reused as oxidizing agent and this active oxygen species is
      reduced to H2O; thereby avoiding oxidative stress by H2O2. Results of our
      structural and functional analyses provide a reasonable explanation of mechanisms
      involved in DHPA synthase-mediated reactions. Based on the key active site
      residue Asn192, identified in Drosophila DHPA synthase, we were able to
      distinguish all available insect DHPA synthases from DDC sequences primarily.

PMID- 29037756
TI  - Colchicine is an active treatment for everolimus-induced oral ulcers.

PMID- 29037757
TI  - Testing Smart Glasses in urology: Clinical and surgical potential applications.
AB  - OBJECTIVES: We aimed to explore the potential benefits of using smart glasses -
      wearable computer optical devices with touch-less command features - in the
      surgery room and in outpatient care settings in urology. MATERIALS AND METHODS:
      Between April and November 2015, 80 urologists were invited to use Google Glass
      in their daily surgical and clinical practice, and to share them with other
      urologists. Participants rated the usefulness of smart glasses on a 10-point
      scale, and provided insights on their potential benefits in a telephone
      interview. RESULTS: During the testing period, 240 urologists used smart glasses,
      and the 80 initially invited rated their usefulness. Mean scores for usefulness
      in the surgery room and in outpatient clinics were 7.4 and 5.4, respectively. The
      interview revealed that the applications of smart glasses considered most
      promising in surgery were live video streaming and static image playback,
      augmented reality, laparoscopic navigation, and digital checklist for safety
      verification. In outpatient settings, participants considered the glasses useful
      as a viewing platform for sharing test results, for browsing digital vademecum,
      and for checking medical records in emergency situations. CONCLUSIONS: Urologists
      engaged in our experience identified various uses of smart glasses with potential
      benefits for physician's daily practice, particularly in the urological surgery
      setting. Further quantitative studies are needed to exploit the actual
      possibilities of smart glasses and address the technical limitations for their
      safe use in clinical and surgical practice.

PMID- 29037758
TI  - The association of vertebrobasilar calcification with etiological subtypes,
      stroke recurrence and outcome in acute brainstem ischemic stroke.
AB  - Arterial calcification (AC), a frequent finding on imaging studies, has been
      reported as a risk factor for ischemic stroke. However few studies have explored
      the association of AC with etiological subtypes and prognostic implications. The
      purpose of this study was to investigate the association of AC with demograhics,
      risk factors and etiological subtypes and to determine whether it predicts stroke
      recurrence and functional outcome in patients with acute brainstem ischemic
      stroke. We analyzed our database consisting of patients who were diagnosed as
      acute brainstem ischemic stroke admitted within 24hours of onset. Etiological
      classification of stroke was made based on The Trial of ORG in Acute Stroke
      Treatment (TOAST) Classification. AC in vertebral and basilar arteries were
      assessed from baseline brain CT. AC degree was categorized according to
      calcification along the circumference in the densest calcified segment of each
      vessel (0 point if no calcification in any of the CT slices, 1 point if
      calcification <50% of circumference and 2 points if calcification >=50% of
      circumference). Three AC categories were defined according to the total AC score
      as follows: no AC (0 point), mild AC (1-2 points), severe AC (>=3 points).
      Recurrent stroke within the first 3 months of follow up and modified Rankin Score
      (mRS) at 3-month were reviewed. 42% of 188 patients had AC in at least of the
      vertebrobasilar arteries. Severe AC was related to age and the presence of
      diabetes mellitus and coronary artery disease. The prevalence of AC was
      significantly higher in large artery atherosclerosis subtype. The presence of AC
      was marginally associated with recurrent stroke but did not find to be related
      with functional outcome. Further studies with larger sample size are warranted to
      explore this topic.

PMID- 29037759
TI  - A New Yeast Peroxin, Pex36, a Functional Homolog of Mammalian PEX16, Functions in
      the ER-to-Peroxisome Traffic of Peroxisomal Membrane Proteins.
AB  - Peroxisomal membrane proteins (PMPs) traffic to peroxisomes by two mechanisms:
      direct insertion from the cytosol into the peroxisomal membrane and indirect
      trafficking to peroxisomes via the endoplasmic reticulum (ER). In mammals and
      yeast, several PMPs traffic via the ER in a Pex3- and Pex19-dependent manner. In
      Komagataella phaffii (formerly called Pichia pastoris) specifically, the indirect
      traffic of Pex2, but not of Pex11 or Pex17, depends on Pex3, but all PMPs tested
      for indirect trafficking require Pex19. In mammals, the indirect traffic of PMPs
      also requires PEX16, a protein that is absent in most yeast species. In this
      study, we isolated PEX36, a new gene in K. phaffii, which encodes a PMP. Pex36 is
      required for cell growth in conditions that require peroxisomes for the
      metabolism of certain carbon sources. This growth defect in cells lacking Pex36
      can be rescued by the expression of human PEX16, Saccharomyces cerevisiae Pex34,
      or by overexpression of the endogenous K. phaffii Pex25. Pex36 is not an
      essential protein for peroxisome proliferation, but in the absence of the
      functionally redundant protein, Pex25, it becomes essential and less than 20% of
      these cells show import-incompetent, peroxisome-like structures (peroxisome
      remnants). In the absence of both proteins, peroxisome biogenesis and the intra
      ER sorting of Pex2 and Pex11C are seriously impaired, likely by affecting Pex3
      and Pex19 function.

PMID- 29037761
TI  - The alpha4beta1/EMILIN1 interaction discloses a novel and unique integrin-ligand
      type of engagement.
AB  - EMILIN1, a homo-trimeric adhesive ECM glycoprotein, interacts with the
      alpha4beta1 integrin through its gC1q domain. Uniquely among the C1q family
      members, the EMILIN1 gC1q presents only nine-stranded beta-sandwich fold and the
      missing strand is substituted by a disordered 19-residue long segment spanning
      from Y927 to G945 at the apex of the gC1q domain. This unstructured loop exposes
      to the solvent the acidic residue E933, which plays a key role in the alpha4beta1
      integrin mediated interaction. Here, we experimentally determined that the three
      E933 residues (one from each monomer) are all required for ligand binding. By
      docking the NMR structure of the gC1q to a virtual alpha4beta1 crystal structure
      based on the known structures of alpha4beta7 and alpha5beta1 integrins we built a
      model of alpha4beta1-gC1q complex where three E933 residues are smoothly forced
      to coordinate the Mg2+ ion at the betaI MIDAS site of the integrin. By bringing
      the three E933 close in space, the trimeric supramolecular organization of gC1q
      allows the formation of a proper 3D geometry and suggests a quaternary-structure
      dependent mode of interaction. Furthermore, we experimentally identified R904 as
      a synergistic residue for cell adhesion. Accordingly, the model showed that this
      residue is able to form potential stabilizing intra-chain salt bridges with
      residues E928 and E930. This mode of interaction likely accounts for a more
      stable and durable alpha4beta1-gC1q interaction in comparison with the prototypic
      CS1 ligand. To our knowledge, this is the first report describing the
      simultaneous involvement of all the three acidic residues of a trimeric ligand in
      the formation of a dimeric complex with the integrin betaI domain.

PMID- 29037760
TI  - Biochemical Differences and Similarities between the DEAD-Box Helicase Orthologs
      DDX3X and Ded1p.
AB  - DDX3X is a conserved DEAD-box RNA helicase involved in translation initiation and
      other processes of RNA metabolism. Mutations in human DDX3X and deregulation of
      its expression are linked to tumorigenesis and intellectual disability. The
      protein is also targeted by diverse viruses. Previous studies demonstrated
      helicase and NTPase activities for DDX3X, but important biochemical features of
      the enzyme remain unclear. Here, we systematically characterize enzymatic
      activities of human DDX3X and compare these to its closely related Saccharomyces
      cerevisiae ortholog Ded1p. We show that DDX3X, like Ded1p, utilizes exclusively
      adenosine triphosphates to unwind helices, oligomerizes to function as efficient
      RNA helicase, and does not unwind DNA duplexes. The ATPase activity of DDX3X is
      markedly stimulated by RNA and weaker by DNA, although DNA binds to the enzyme.
      For RNA unwinding, DDX3X shows a greater preference than Ded1p for substrates
      with unpaired regions 3' to the duplex over those with 5' unpaired regions. DDX3X
      separates longer RNA duplexes faster than Ded1p and is less potent than Ded1p in
      facilitating strand annealing. Our results reveal that the biochemical activities
      of human DDX3X are typical for DEAD-box RNA helicases, but diverge quantitatively
      from its highly similar S. cerevisiae ortholog Ded1p.

PMID- 29037762
TI  - Evaluation of lesion flow coefficient for the detection of coronary artery
      disease in patient groups from two academic medical centers.
AB  - BACKGROUND: In this study, lesion flow coefficient (LFC: ratio of % area stenosis
      [%AS] to the square root of the ratio of the pressure drop across the stenosis to
      the dynamic pressure in the throat region), that combines both the anatomical
      (%AS) and functional measurements (pressure and flow), was assessed for
      application in a clinical setting. METHODS AND RESULTS: Pressure, flow, and
      anatomical values were obtained from patients in 251 vessels from two different
      centers. Fractional flow reserve (FFR), Coronary flow reserve (CFR), hyperemic
      stenosis resistance index (HSR) and hyperemic microvascular index (HMR) were
      calculated. Anatomical data was corrected for the presence of guidewire and the
      LFC values were calculated. LFC was correlated with FFR, CFR, HSR, HMR,
      individually and in combination with %AS. The p<0.05 was used for statistical
      significance. LFC correlated significantly when the FFR (pressure-based), CFR
      (flow-based), and anatomical measure %AS were combined (r=0.64; p<0.05).
      Similarly, LFC correlated significantly when HSR, HMR, and %AS were combined
      (r=0.72; p<0.05). LFC was able to significantly (p<0.05) distinguish between the
      two concordant and the two discordant groups of FFR and CFR, corresponding to the
      clinically used cut-off values (FFR=0.80 and CFR=2.0). The LFC could also
      significantly (p<0.05) distinguish between the normal and abnormal
      microvasculature conditions in the presence of non-significant epicardial
      stenosis, while the comparison was borderline significant (p=0.09) in the
      presence of significant stenosis. CONCLUSION: LFC, a parameter that combines both
      the anatomical and functional end-points, has the potential for application in a
      clinical setting for CAD evaluation.

PMID- 29037764
TI  - [Evaluation of the efficacy of lidocaine and magnesium sulphate in reducing the
      hemodynamic effects caused after intubation/laryngoscopy].

PMID- 29037763
TI  - Aortic pseudoaneurysm & endocarditis caused by Aerococcus viridans: A case report
      and literature review.
AB  - Aerococcus viridans is a gram positive microaerophilic lactic acid coccus which
      is known to cause an infection in lobsters called Gaffkaemia. Consumption of
      gaffekaemia affected lobsters is considered to be safe if properly cooked even
      though there hasn't been any research on potential transmission by this route.
      Though uncommon, A. viridans is capable of causing a virulent endocarditis
      associated with aortic valve destruction and abscess. There have been 11
      worldwide reported cases of infective endocarditis, of which 6 were aortic and
      only one of them had aortic pseudoaneurysm (APA). We review these cases and also
      present the case of a 32-year-old young man with no risk factors who presented
      initially with native valve endocarditis with aerococcus viridans and
      subsequently with large aortic pseudo-aneurysm.

PMID- 29037765
TI  - Mechanisms Causing Loss of Keratinocyte Cohesion in Pemphigus.
AB  - The autoimmune blistering skin disease pemphigus is caused by IgG autoantibodies
      against desmosomal cadherins, but the precise mechanisms are in part a matter of
      controversial discussions. This review focuses on the currently existing models
      of the disease and highlights the relevance of desmoglein-specific versus
      nondesmoglein autoantibodies, the contribution of nonautoantibody factors, and
      the mechanisms leading to cell dissociation and blister formation in response to
      autoantibody binding. As the review brings together the majority of laboratories
      currently working on pemphigus pathogenesis, it aims to serve as a solid basis
      for further investigations for the entire field.

PMID- 29037766
TI  - Frequency and Markers of Precursor Lesions and Implications for the Pathogenesis
      of Testicular Germ Cell Tumors.
AB  - BACKGROUND: The World Health Organization classification of urologic cancer 2016
      describes 3 noninvasive precursor lesions for testicular germ cell tumor type II
      (TGCT) of young adults. Germ cell neoplasia in situ is the initial precursor
      lesion. Intratubular seminoma (ITSE), and intratubular embryonal carcinoma (ITEC)
      are 2 intermediate precursor lesions. Microinvasive testicular germ cell tumor
      (MGCT) is an invasive precursor lesion. MATERIALS AND METHODS: We undertook a
      retrospective study of testes obtained using orchiectomy for TGCT and examined
      precursor lesions. The examinations included immunohistochemical staining of the
      precursor lesions for octamer-binding transcription factor 4 (OCT4), CD117, and
      CD30. We examined 63 consecutive and evaluable patients. RESULTS: Of the
      patients, 44 had seminoma and 19 had a nonseminomatous TGCT. MGCT was more
      frequent than ITSE (P = .002; chi2 test). None of the testes had ITEC.
      Immunohistochemistry showed that 72 of 77 precursor lesions (93%) stained
      positive for OCT4 and CD117 and negative for CD30. The pattern represents a
      seminomatous immunophenotype. A meta-analysis of the published studies regarding
      precursor lesions included 1007 patients. Overall, the pooled rate of ITSE was
      29% (95% confidence interval [CI], 18%-40%) and the pooled rate of MGCT was 21%
      (95% CI, 15%-27%). CONCLUSION: MGCT is a frequent intermediate precursor lesion.

PMID- 29037767
TI  - DT-13 synergistically potentiates the sensitivity of gastric cancer cells to
      topotecan via cell cycle arrest in vitro and in vivo.
AB  - Natural medicine has multi-levels, multi-paths and multi-targets, and an
      increasing number of reports have confirmed that the combination of natural
      medicine with chemotherapy drugs exhibit a significant synergistic effect. It is
      necessary to find drug combination strategies to enhance efficacy and reduce
      toxicity, which can relieve the restrictions on the use of several chemotherapy
      drugs that have serious toxicity. Our previous reports showed that DT-13 inhibits
      cancer proliferation, invasion, migration, metastasis, and angiogenesis and
      induces autophagy. In this study, we evaluated the anti-proliferation effect of
      DT-13 on a panel of 40 different cancer cell lines for the first time. Moreover,
      it is also the first time that the combination of DT-13 with 5 different
      chemotherapy drugs on 3 common cancer cells has been examined. We further
      confirmed that DT-13 enhanced the sensitivity of gastric cancer cells to
      topotecan (TPT) via cell cycle arrest in vitro and in vivo. Considering that TPT
      has been subjected to restriction because of its serious toxicity, DT-13 showed
      the ability to enhance its effect and reduce its toxicity, which could provide a
      strategy to reduce the toxic and clinical side effects of TPT.

PMID- 29037768
TI  - Potential of macroalgae for biodiesel production: Screening and evaluation
      studies.
AB  - Nowadays, biofuel production is a fast expanding industry and is facing a growing
      dilemma about a feedstock source capable of keeping up with demand. Recently,
      macroalgae have been attracting a wide attention as a source for biofuel. In the
      present study, ten macroalgae were collected and screened as biodiesel
      feedstocks. As a result of their high biomass production and relatively high
      lipid content, Ulva lactuca, Padina boryana and Ulva intestinalis showed the
      highest significant lipids and fatty acid methyl esters (FAMEs) areal
      productivities among the studied species. Saturated fatty acids (SAFs) showed
      insignificant differences in the selected species, with noticeably significant
      higher polyunsaturated fatty acids (PUFAs) content in U. lactuca by 4.2 and 3
      times, with respect to P. boryana and U. intestinalis, respectively. The recorded
      increase in PUFAs was attributed to higher content of C16:4n-3, C18:3n-3 and
      C18:4n-3. By lipid fractionation, P. boryana showed significant higher
      concentration of neutral lipids (37.7 mg g-1 CDW, representing 46.7% of total
      fatty acids) in comparison to U. lactuca and U. intestinalis, which showed 16%
      and 17% lower neutral lipid fractions, respectively. In addition, biodiesel
      characteristics of the studied macroalgae complied with that of international
      standards. Furthermore, oil-free residual biomass can be readily converted into
      fermentable sugars or biogas due to its high carbohydrates content, which adds to
      the economics of macroalgae as biofuel feedstock. In conclusion, the present
      study confirmed that macroalgae represent an attractive alternative renewable
      feedstock for biodiesel and other biofuels.

PMID- 29037769
TI  - Activation of respiratory muscles during respiratory muscle training.
AB  - It is unknown which respiratory muscles are mainly activated by respiratory
      muscle training. This study evaluated Inspiratory Pressure Threshold Loading
      (IPTL), Inspiratory Flow Resistive Loading (IFRL) and Voluntary Isocapnic
      Hyperpnea (VIH) with regard to electromyographic (EMG) activation of the
      sternocleidomastoid muscle (SCM), parasternal muscles (PARA) and the diaphragm
      (DIA) in randomized order. Surface EMG were analyzed at the end of each training
      session and normalized using the peak EMG recorded during maximum inspiratory
      maneuvers (Sniff nasal pressure: SnPna, maximal inspiratory mouth occlusion
      pressure: PImax). 41 healthy participants were included. Maximal activation was
      achieved for SCM by SnPna; the PImax activated predominantly PARA and DIA.
      Activations of SCM and PARA were higher in IPTL and VIH than for IFRL (p<0.05).
      DIA was higher applying IPTL compared to IFRL or VIH (p<0.05). IPTL, IFRL and VIH
      differ in activation of inspiratory respiratory muscles. Whereas all methods
      mainly stimulate accessory respiratory muscles, diaphragm activation was
      predominant in IPTL.

PMID- 29037771
TI  - Factors Affecting Jordanian School Adolescents' Experience of Being Bullied.
AB  - PURPOSE: The purpose of this study was to identify the Jordanian school
      adolescents' experience of being bullied, and to examine its association with
      selected socio-demographic variables. DESIGN AND METHODS: This cross sectional
      descriptive study used multi-stages cluster sampling technique to recruit a
      sample of in-school adolescents in Jordan (N=436). The Personal Experiences
      Checklist was used to measure the experience of bullying. Descriptive statistics
      and parametric tests were used in the analysis. RESULTS: Relational-verbal
      bullying was the most common form of bullying while cyber bullying was the least
      common type. Male adolescents experienced bullying more than females. In
      addition, adolescents belonging to low-income families experienced bullying more
      than those from moderate-income families. Finally, being bullied was negatively
      correlated with academic performance of students. CONCLUSIONS: This study
      indicated that risk factors for bullying are multifaceted which necessitate the
      development of prevention and intervention strategies to combat bullying taking
      into consideration these factors. PRACTICE IMPLICATIONS: Schools should introduce
      environmental changes to discourage bullying and establish a policy with specific
      guidelines of what constitutes bullying behavior and expected disciplinary
      procedures. Staff training on information about the definition of bullying,
      current trends, and the effects of bullying is also recommended.

PMID- 29037770
TI  - Dietary nitrate supplementation opposes the elevated diaphragm blood flow in
      chronic heart failure during submaximal exercise.
AB  - Chronic heart failure (CHF) results in a greater cost of breathing and
      necessitates an elevated diaphragm blood flow (BF). Dietary nitrate (NO3?)
      supplementation lowers the cost of exercise. We hypothesized that dietary NO3?
      supplementation would attenuate the CHF-induced greater cost of breathing and
      thus the heightened diaphragm BF during exercise. CHF rats received either 5days
      of NO3?-rich beetroot (BR) juice (CHF+BR, n=10) or a placebo (CHF, n=10).
      Respiratory muscle BFs (radiolabeled microspheres) were measured at rest and
      during submaximal exercise (20m/min, 5% grade). Infarcted left ventricular area
      and normalized lung weight were not significantly different between groups.
      During submaximal exercise, diaphragm BF was markedly lower for CHF+BR than CHF
      (CHF+BR: 195+/-28; CHF: 309+/-71mL/min/100g, p=0.04). The change in diaphragm BF
      from rest to exercise was less (p=0.047) for CHF+BR than CHF. These findings
      demonstrate that dietary NO3? supplementation reduces the elevated diaphragm BF
      during exercise in CHF rats thus providing additional support for this
      therapeutic intervention in CHF.

PMID- 29037772
TI  - Family Health Conversations at a Pediatric Oncology Center - A Way for Families
      to Rebalance the Situation.
AB  - PURPOSE: The study aimed to describe and understand adult family members'
      experiences of participating in a Family Health Conversation (FamHC) when a child
      is diagnosed with cancer. DESIGN AND METHODS: Twelve individual interviews were
      performed with adult family members who had participated in a FamHC. During the
      interviews each interviewee was a spokesman for his or her respective family.
      Thereby the family was included as a system. The interviews were analyzed using a
      hermeneutic approach. RESULTS: The analysis resulted in four themes: "To unburden
      the burden," "Seeing things in a new light," "To be seen the way you are," and
      "Talking to someone who is both within and alongside." Finally an overarching
      theme evolved, "To rebalance the situation" revealing the meaning of taking part
      in the FamHC. CONCLUSION: All participants considered the FamHC to be valuable.
      It was surprising that such a relatively small investment of two family
      conversations and a closing letter could have such significance for the families
      in their difficult situation. PRACTICE IMPLICATIONS: With training, clinical
      nurses can use a well-established structured interview process such as the Family
      Health Conversation to help family members to gain insight into each other's
      experiences, which increase their ability to cope and regain control.

PMID- 29037773
TI  - Use of N-acetylcysteine plus simethicone to improve mucosal visibility during
      upper GI endoscopy: a double-blind, randomized controlled trial.
AB  - BACKGROUND AND AIM: Upper GI endoscopy (UGE) is essential for the diagnosis of
      gastrointestinal diseases. Mucus and bubbles may decrease mucosal visibility. The
      use of mucolytics could improve visualization. Our aim was to determine whether
      premedication with simethicone or simethicone plus N-acetylcysteine is effective
      in improving visibility during UGE. METHODS: This was a randomized, double
      blinded, placebo-controlled trial with 2 control groups: no intervention and
      water 100 mL (W); and 3 intervention groups: simethicone 200 mg (S); S + N
      acetylcysteine (NAC) 500 mg (S+NAC500); and S + NAC 1000 mg (S+NAC1000). The
      solution was ingested 20 minutes before UGE. Gastric visibility was evaluated in
      4 segments with a previously described scale. A score of less than 7 points was
      defined as adequate visibility (AV). Water volume was used to improve visibility,
      and adverse reactions were evaluated as a secondary outcome. Multiple group
      comparison was performed using non-parametric one-way analysis of variance
      (ANOVA). RESULTS: Two hundred thirty patients were included in the study, 68%
      female, mean age 49 years. The most common indication for UGE was epigastric
      pain/dyspepsia (33%). AV was more frequent in the S+NAC500 and S+NAC1000 groups
      (65% and 67%) compared with no intervention (44%, P = .044) and water (41%, P =
      .022). The gastric total visibility scale (TVS) was significantly better in the
      S+NAC500 and S+NAC1000 groups compared with water (P = .03 and P = .008).
      Simethicone was not different from no intervention and water. S+NAC1000 required
      less water volume to improve visibility. No adverse reactions from the study
      drugs were observed. CONCLUSIONS: Premedication with S+NAC500 and S+NAC1000
      improves visibility during UGE. The use of simethicone did not show improvements
      in gastric visibility. TVS was worse in patients using water alone. (Clinical
      trial registration number: NCT 01653171.).

PMID- 29037774
TI  - Framework for the quantitative weight-of-evidence analysis of 'omics data for
      regulatory purposes.
AB  - A framework for the quantitative weight-of-evidence (QWoE) analysis of 'omics
      data for regulatory purposes is presented. The QWoE framework encompasses seven
      steps to evaluate 'omics data (also together with non-'omics data): (1)
      Hypothesis formulation, identification and weighting of lines of evidence (LoEs).
      LoEs conjoin different (types of) studies that are used to critically test the
      hypothesis. As an essential component of the QWoE framework, step 1 includes the
      development of templates for scoring sheets that predefine scoring criteria with
      scores of 0-4 to enable a quantitative determination of study quality and data
      relevance; (2) literature searches and categorisation of studies into the pre
      defined LoEs; (3) and (4) quantitative assessment of study quality and data
      relevance using the respective pre-defined scoring sheets for each study; (5)
      evaluation of LoE-specific strength of evidence based upon the study quality and
      study relevance scores of the studies conjoined in the respective LoE; (6)
      integration of the strength of evidence from the individual LoEs to determine the
      overall strength of evidence; (7) characterisation of uncertainties and
      conclusion on the QWoE. To put the QWoE framework in practice, case studies are
      recommended to confirm the relevance of its different steps, or to adapt them as
      necessary.

PMID- 29037775
TI  - Neuroendocrine late effects after tailored photon radiotherapy for children with
      low grade gliomas: Long term correlation with tumour and treatment parameters.
AB  - PURPOSE: To evaluate neuroendocrine late effects in paediatric patients with low
      grade glioma (LGG) who underwent radiotherapy. METHODS AND MATERIAL: We performed
      a retrospective evaluation of 40 children with LGG treated from July 2002 to
      January 2015 with external radiotherapy. Tumour locations were cerebral
      hemisphere (n=2); posterior fossa (n=15); hypothalamic-pituitary axis (HPA,
      n=15); spine (n=5). Three patients presented a diffuse disease. We looked for a
      correlation between endocrine toxicity and tumour and treatment parameters. The
      impact of some clinical and demographic factors on endocrinal and neuro toxicity
      was evaluated using the log-rank test. RESULTS: The median follow-up was 52months
      (range: 2-151). Median age at irradiation was 6. The dose to the HPA was
      significantly associated with endocrine toxicity (P value=0.0190). Patients who
      received chemotherapy before radiotherapy and younger patients, showed worse
      performance status and lower IQ. The 5-year overall survival (OS) and progression
      free survival (PFS) rates were 94% and 73.7%, respectively. CONCLUSION:
      Radiotherapy showed excellent OS and PFS rates and acceptable late neuroendocrine
      toxicity profile in this population of LGG patients treated over a period of
      13years. In our experience, the dose to the HPA was predictive of the risk of
      late endocrine toxicity.

PMID- 29037776
TI  - A multicentre 'end to end' dosimetry audit of motion management (4DCT-defined
      motion envelope) in radiotherapy.
AB  - PURPOSE: External dosimetry audit is valuable for the assurance of radiotherapy
      quality. However, motion management has not been rigorously audited, despite its
      complexity and importance for accuracy. We describe the first end-to-end
      dosimetry audit for non-SABR (stereotactic ablative body radiotherapy) lung
      treatments, measuring dose accumulation in a moving target, and assessing
      adequacy of target dose coverage. MATERIALS AND METHODS: A respiratory motion
      lung-phantom with custom-designed insert was used. Dose was measured with
      radiochromic film, employing triple-channel dosimetry and uncertainty reduction.
      The host's 4DCT scan, outlining and planning techniques were used. Measurements
      with the phantom static and then moving at treatment delivery separated inherent
      treatment uncertainties from motion effects. Calculated and measured dose
      distributions were compared by isodose overlay, gamma analysis, and we introduce
      the concept of 'dose plane histograms' for clinically relevant interpretation of
      film dosimetry. RESULTS: 12 radiotherapy centres and 19 plans were audited:
      conformal, IMRT (intensity modulated radiotherapy) and VMAT (volumetric modulated
      radiotherapy). Excellent agreement between planned and static-phantom results
      were seen (mean gamma pass 98.7% at 3% 2 mm). Dose blurring was evident in the
      moving-phantom measurements (mean gamma pass 88.2% at 3% 2 mm). Planning
      techniques for motion management were adequate to deliver the intended moving
      target dose coverage. CONCLUSIONS: A novel, clinically-relevant, end-to-end
      dosimetry audit of motion management strategies in radiotherapy is reported.

PMID- 29037777
TI  - Multipotency of skeletal muscle stem cells on their native substrate and the
      expression of Connexin 43 during adoption of adipogenic and osteogenic fate.
AB  - Muscle regeneration is performed by resident muscle stem cells called satellite
      cells (SC). However they are multipotent, being able to adopt adipogenic and
      osteogenic fate under the correct stimuli. Since SC behavior can be regulated by
      the extra-cellular matrix, we examined the robustness of the myogenic programme
      of SC on their native substrate-the surface of a myofiber. We show that the
      native substrate supports myogenic differentiation judged by the expression of
      members of the Myogenic Determination Factor (MRF) family. However SC even on
      their native substrate can be induced into adopting adipogenic or osteogenic
      fate. Furthermore conditions that support adipose or bone formation inhibit the
      proliferation of SC progeny as well as their migration. We show that Connexin43
      (Cx43), a gap junction complex protein, is only expressed by activated and not
      quiescent SC. Furthermore, it is not expressed by SC that are in the process of
      changing their fate. Lastly we show that intact adult mouse muscle contains
      numerous cells expressing Cx43 and that the density of these cells seems to be
      related to capillary density. We suggest the Cx43 expression is localized to
      angioblasts and is more prominent in oxidative slow muscle compared to glycolytic
      fast muscle.

PMID- 29037778
TI  - Orientia tsutsugamushi infection in rodents in Anhui Province of China.
AB  - We conducted an investigation of Orientia tsutsugamushi infection among rodents
      in non-endemic areas in Anhui Province. Fifty-six (56) rodents including 44
      Apodemus agrarius and 12 Niviventer niviventer were trapped and captured in
      autumn in the fields of three counties in Anhui Province. DNA samples were
      amplified and sequenced for the 56kDa protein gene of Orientia tsutsugamushi. The
      overall infection rate in the rodents was 23.2%(13/56). The rate of detection of
      O. tsutsugamushi in Apodemus agrarius and Niviventer niviventer were 27.3% and
      8.3% respectively. Moreover, we identified two genotypes (Karp and Gilliam
      strains) of Orientia tsutsugamushi in rodents. Our study demonstrated that
      Apodemus agrarius is the main host for O. tsutsugamushi pathogen and this is the
      first report of Karp and Gilliam strains in these non-endemic areas in Anhui
      Province.

PMID- 29037780
TI  - Bio-based succinate from sucrose: High-resolution 13C metabolic flux analysis and
      metabolic engineering of the rumen bacterium Basfia succiniciproducens.
AB  - Succinic acid is a platform chemical of recognized industrial value and
      accordingly faces a continuous challenge to enable manufacturing from most
      attractive raw materials. It is mainly produced from glucose, using microbial
      fermentation. Here, we explore and optimize succinate production from sucrose, a
      globally applied substrate in biotechnology, using the rumen bacterium Basfia
      succiniciproducens DD1. As basis of the strain optimization, the yet unknown
      sucrose metabolism of the microbe was studied, using 13C metabolic flux analyses.
      When grown in batch culture on sucrose, the bacterium exhibited a high succinate
      yield of 1molmol-1 and a by-product spectrum, which did not match the expected
      PTS-mediated sucrose catabolism. This led to the discovery of a fructokinase,
      involved in sucrose catabolism. The flux approach unraveled that the fructokinase
      and the fructose PTS both contribute to phosphorylation of the fructose part of
      sucrose. The contribution of the fructokinase reduces the undesired loss of the
      succinate precursor PEP into pyruvate and into pyruvate-derived by-products and
      enables increased succinate production, exclusively via the reductive TCA cycle
      branch. These findings were used to design superior producers. Mutants, which (i)
      overexpress the beneficial fructokinase, (II) lack the competing fructose PTS,
      and (iii) combine both traits, produce significantly more succinate. In a fed
      batch process, B. succiniciproducens DeltafruA achieved a titer of 71gL-1
      succinate and a yield of 2.5molmol-1 from sucrose.

PMID- 29037779
TI  - 13C metabolic flux analysis of three divergent extremely thermophilic bacteria:
      Geobacillus sp. LC300, Thermus thermophilus HB8, and Rhodothermus marinus DSM
      4252.
AB  - Thermophilic organisms are being increasingly investigated and applied in
      metabolic engineering and biotechnology. The distinct metabolic and physiological
      characteristics of thermophiles, including broad substrate range and high uptake
      rates, coupled with recent advances in genetic tool development, present unique
      opportunities for strain engineering. However, poor understanding of the cellular
      physiology and metabolism of thermophiles has limited the application of systems
      biology and metabolic engineering tools to these organisms. To address this
      concern, we applied high resolution 13C metabolic flux analysis to quantify
      fluxes for three divergent extremely thermophilic bacteria from separate phyla:
      Geobacillus sp. LC300, Thermus thermophilus HB8, and Rhodothermus marinus DSM
      4252. We performed 18 parallel labeling experiments, using all singly labeled
      glucose tracers for each strain, reconstructed and validated metabolic network
      models, measured biomass composition, and quantified precise metabolic fluxes for
      each organism. In the process, we resolved many uncertainties regarding gaps in
      pathway reconstructions and elucidated how these organisms maintain redox balance
      and generate energy. Overall, we found that the metabolisms of the three
      thermophiles were highly distinct, suggesting that adaptation to growth at high
      temperatures did not favor any particular set of metabolic pathways. All three
      strains relied heavily on glycolysis and TCA cycle to generate key cellular
      precursors and cofactors. None of the investigated organisms utilized the Entner
      Doudoroff pathway and only one strain had an active oxidative pentose phosphate
      pathway. Taken together, the results from this study provide a solid foundation
      for future model building and engineering efforts with these and related
      thermophiles.

PMID- 29037781
TI  - Uncovering the role of branched-chain amino acid transaminases in Saccharomyces
      cerevisiae isobutanol biosynthesis.
AB  - Isobutanol and other branched-chain higher alcohols (BCHAs) are promising
      advanced biofuels derived from the degradation of branched-chain amino acids
      (BCAAs). The yeast Saccharomyces cerevisiae is a particularly attractive host for
      the production of BCHAs due to its high tolerance to alcohols and prevalent use
      in the bioethanol industry. Degradation of BCAAs begins with transamination
      reactions, catalyzed by branched-chain amino acid transaminases (BCATs) located
      in the mitochondria (Bat1p) and cytosol (Bat2p). However, the roles that these
      transaminases play in isobutanol production remain poorly understood and obscured
      by conflicting reports in the literature. In this work, we elucidate the
      influence of BCATs on isobutanol production in two genetic backgrounds (CEN.PK2
      1C and BY4741). In the process, we uncover and characterize two competing
      isobutanol pathways, which can be manipulated by overexpressing or deleting BAT1
      or BAT2, and adding or removing valine from the fermentation media. We show that
      deletion of BAT1 alone increases isobutanol production by 14.2-fold over wild
      type strains in media lacking valine, and examine how interactions between valine
      and the regulatory protein Ilv6p affect isobutanol production. Compartmentalizing
      the five-gene isobutanol biosynthetic pathway in mitochondria of BAT1 deletion
      strains results in an additional 2.1-fold increase in isobutanol production in
      the absence of valine. While valine inhibits isobutanol production, it boosts 2
      methyl-1-butanol production. This work clarifies the role of transamination
      activity in BCHA biosynthesis, and develops valuable strategies and strains for
      future optimization of isobutanol production.

PMID- 29037782
TI  - Paeoniflorin targets apoptosis and ameliorates fibrosis in murine schistosomiasis
      mansoni: A novel insight.
AB  - Schistosomiasis is a chronic helminthic disease causing hepatic fibrosis. Some
      studies demonstrated direct effect of targeting apoptosis on fibrosis regression.
      This study is a novel trial of Paeoniflorin (PAE) on S. mansoni induced hepatic
      fibrosis in murine model compared to Praziquantel (PZQ) evaluating their anti
      parasitic and anti-fibrotic properties aiming to discover a new therapy that
      decrease schistosomiasis morbidity. Thirty two laboratory bred Swiss albino male
      CD-1 mice were used in this study. The mice were classified into four groups (8
      mice each), control healthy, control infected, PZQ treated (300 mg/kg/12 h), PAE
      treated (50 mg/kg/d) groups. All mice groups were sacrificed 15 weeks post
      infection for assessment of drugs efficacy by parasitological, histopathological,
      immunohistochemical and serological studies. Our results showed that PAE improved
      the parasitological parameters including decrease worm burden, immature, mature
      eggs and increase dead ones yet, still PZQ had the upper hand in this aspect.
      However, PAE exceeded PZQ as an anti-fibrotic therapy seemed in marked decrease
      in hepatic mean granuloma diameter and fibrosis area, besides, marked increase in
      serum tumor necrosis factor-alpha; TNF-alpha level, caspase-3 and P53 apoptotic
      expressions. There was marked decrease in serum IL-13 level, nuclear factor-kappa
      B; NF-kB, Transforming Growth Factor-Beta1; TGF-beta1, Alpha-Smooth Muscle Actin;
      alpha-SMA fibrotic expressions. Conclusively, PAE could be an anti
      schistosomiasis mansoni therapy exceeding PZQ in targeting apoptosis and
      ameliorating fibrosis. This study provides a perspective for a novel therapeutic
      approach to prevent liver fibrosis following liver injury due to schistosomiasis
      mansoni.

PMID- 29037783
TI  - Suppression of nemo-like kinase by miR-71 in Echinococcus multilocularis.
AB  - Echinococcus multilocularis metacestodes are a causative pathogen for alveolar
      echinococcosis in human beings, and have been found to express miRNAs including
      emu-miR-71. miR-71 is evolutionarily conserved and highly expressed across
      platyhelminths, but little is known about its role. Here it was shown that emu
      miR-71 was differentially expressed in protoscoleces and was unlikely to be
      expressed in neoblasts. The results of the luciferase assay indicated that emu
      miR-71 was able to bind in vitro to the 3'-UTR of emu-nlk, encoding a key
      regulator of cell division, causing significant downregulation of luciferase
      activity (p < 0.01) compared to the negative control and the construct with
      mutations in the binding site. Consistent with the decreased luciferase activity,
      transfection of emu-miR-71 mimics into protoscoleces notably repressed emu-NLK (p
      < 0.05). These results demonstrate the suppression of emu-nlk by emu-miR-71,
      potentially involved in the protoscolex development.

PMID- 29037784
TI  - The influence of registered nurses and nurse practitioners on patient experience
      with primary care: results from the Canadian QUALICO-PC study.
AB  - Nurses, whether registered nurses (RNs) or nurse practitioners (NPs), are
      becoming key providers of primary care services. While evidence for the influence
      of NPs on patient experience in primary care is mounting, this is less so for
      RNs. We use the Canadian component of the international Quality and Costs of
      Primary Care 2013/14 survey to investigate the mechanisms by which nurses can
      affect patients' experience in primary care, focusing on accessibility and
      appropriateness of care. The data allow us to distinguish between family practice
      RNs, specialised RNs and NPs, and covers all types of patients visiting a primary
      care clinic in a variety of contexts in all Canadian provinces. In addition to
      the types of nurses and full-time equivalent (FTE) numbers, we explore the role
      of nurse autonomy and collaboration. Our regression results show that one of the
      most important predictors of patient experience is the collaboration between
      health professionals, whereas nurse staffing in terms of FTE numbers has little
      influence by itself. Different types of nurses influence different dimensions of
      accessibility, and the association between patient experience and nurse staffing
      depends on the number of physicians in the clinic. Our results can inform
      decision-makers on how to strengthen primary care provision, and particularly in
      Canadian context, the adaptation of the recently implemented interprofessional
      primary care teams.

PMID- 29037785
TI  - Novel bilayer dissolving microneedle arrays with concentrated PLGA nano
      microparticles for targeted intradermal delivery: Proof of concept.
AB  - Polymeric microneedle (MN) arrays continue to receive growing attention due to
      their ability to bypass the skin's stratum corneum barrier in a minimally
      invasive fashion and achieve enhanced transdermal drug delivery and "targeted"
      intradermal vaccine administration. In this research work, we fabricated
      biodegradable bilayer MN arrays containing nano - microparticles for targeted and
      sustained intradermal drug delivery. For this study, model drug (vitamin D3, VD3)
      loaded PLGA nano- and microparticles (NMP) were prepared by a single emulsion
      solvent evaporation method with 72.8% encapsulation of VD3. The prepared NMP were
      directly mixed 20% w/v poly(vinyl pyrrolidone) (PVP) gel, with the mixture filled
      into laser engineered micromoulds by high-speed centrifugation (30min) to
      concentrate NMP into MN shafts. The particle size of PLGA NMP ranged from 300nm
      to 3.5MUm and they retained their particle size after moulding of bilayer MN
      arrays. The relatively wide particle size distribution of PLGA NMP was shown to
      be important in producing a compact structure in bilayer conical, as well as
      pyramidal, MN, as confirmed by scanning electron microscopy. The drug release
      profile from PLGA NMP was tri-phasic, being sustained over 5days. The height of
      bilayer MN arrays was influenced by the weight ratio of NMP and 20% w/v PVP. Good
      mechanical and insertion profiles (into a skin simulant and excised neonatal
      porcine skin) were confirmed by texture analysis and optical coherence
      tomography, respectively. Ex vivo intradermal neonatal porcine skin penetration
      of VD3 NMP from bilayer MN was quantitatively analysed after cryostatic skin
      sectioning, with 74.2+/-9.18% of VD3 loading delivered intradermally. The two
      stage novel processing strategy developed here provides a simple and easy method
      for localising particulate delivery systems into dissolving MN. Such systems may
      serve as promising means for controlled transdermal delivery and targeted
      intradermal administration.

PMID- 29037786
TI  - Changes in Postural Sway After a Single Global Postural Reeducation Session in
      University Students: A Randomized Controlled Trial.
AB  - OBJECTIVE: The purpose of this study was to assess the effectiveness of a single
      session of global postural reeducation (GPR) in postural sway in young adult
      university students who use data visualization screens. METHODS: A randomized
      controlled trial with 2 parallel groups was performed. Sixty-four subjects were
      randomized in the experimental group (12 men and 20 women) who underwent the GPR
      session, and a control group (13 men and 19 women) that did not receive any
      intervention was included. Center of pressure (COP) was assessed using a
      stabilometric platform, with eyes open and eyes closed before, immediately after,
      48 hours after, and 7 days after intervention in both groups. RESULTS: In the
      interaction of time and gender, statistically significant differences were found
      for the area covered by COP (P = .020) and for the standard deviation (SD) in the
      mediolateral axis (P = .035). Considering the complete interaction time, gender,
      and group, statistically significant differences were found (P = .015) for the
      anteroposterior rate covered by COP and the SD in the anteroposterior axis (P =
      .033). In eyes closed condition, the intersubject analysis showed statistically
      significant differences for the interaction between group and gender for the
      variable mediolateral SD (P = .043). Considering the interaction of time with
      group, statistically significant differences were found for full length covered
      by COP (P = .017). CONCLUSIONS: Changes in postural sway were observed after a
      single GPR session, mainly at 48 hours, with different behaviors between men and
      women.

PMID- 29037787
TI  - The Relationship Between Spinal Pain and Comorbidity: A Cross-sectional Analysis
      of 579 Community-Dwelling, Older Australian Women.
AB  - OBJECTIVES: The aims of this study were to (1) report the prevalence and explore
      the influence of spinal pain on quality of life and (2) assess the relationship
      between spinal pain and the type and number of comorbidities. METHODS: This cross
      sectional study comprised 579 community-dwelling, older Australian women. Women
      had "spinal pain" if they marked "yes" to neck pain, upper back pain, mid-back
      pain, and/or lower back pain. Descriptive statistics and binary logistic
      regression were performed to report the prevalence and explore the relationship
      between spinal pain and the type and number of comorbidities. RESULTS: A majority
      of women (55.8%) who returned surveys had spinal pain. Women with spinal pain had
      significantly lower physical and mental quality of life scores than women without
      spinal pain (Medical Outcomes Study: 36 Item Short Form Survey [SF-36] physical
      component summary: 40.1 +/- 11.1 vs 49.0 +/- 9.0, and SF-36 mental component
      summary: 50.0 +/- 10.5 vs 53.9 +/- 8.2, respectively). Having spinal pain was
      significantly associated with overweight and obesity (odds ratio 1.98 [95%
      confidence interval 1.3-2.96] and 2.12 [1.37-3.28]), diabetes (1.93 [1.01-3.67]),
      pulmonary comorbidity (1.66 [1.04-2.65]), and cardiovascular comorbidity (1.57
      [1.07-2.28]). More than half of the women with spinal pain reported 2 or more
      comorbidities, with comorbidities significantly more common among women with
      spinal pain than among women without spinal pain. The odds of having spinal pain
      increased with an increasing number of comorbidities (2 comorbidities: 2.44 [1.47
      4.04], 3 comorbidities: 3.07 [1.66-5.67], 4 comorbidities: 5.05 [1.64-15.54]).
      CONCLUSIONS: Spinal pain is common in community-dwelling, older Australian women
      and is associated with greater disability and poorer quality of life. Diabetes,
      cardiovascular disease, pulmonary disease, and obesity appear to have a
      relationship with spinal pain. There was an incremental increase in the risk of
      spinal pain associated with increasing comorbidity count.

PMID- 29037788
TI  - [Primary care evaluation of the hypertensive patient management in specialized
      care after derivation (DERIVA-2 Study)].
AB  - INTRODUCTION: To know the opinion/evaluation of the primary care physicians
      (PCPH) of the received information about patients that were attended in
      specialized care (SC). DESIGN: Cross-sectional study. LOCATION: Performed
      nationwide in primary care centers. PARTICIPANTS: Researchers from the primary
      care network. METHODS: We used the SEH-LELHA derivation criteria guidelines, plus
      an ad hoc survey that included demographic and anthropometric data, blood
      pressure levels, and the main reason for derivation to SC at the baseline and
      final (post-derivation) visit. In addition, time deployed for the study of every
      patient, changes in diagnosis and treatment, type of follow-up, issues throughout
      the derivation process and assessment of the medical referred to the PCPH were
      evaluated. RESULTS: With participation of 578 researchers from primary, the study
      included 1715 patients aged 60.7+/-13.3years, 62.7% male. Patients were taking
      2.3+/-1.2 (range 0-10) antihypertensive drugs pre-referral and 2.5+/-1.2 (0-9)
      after derivation. Blood pressure levels changed from 166+/-21.6 /97.7+/-12.6mmHg
      to 143+/-14.4 /85.5+/-10.5mmHg. The number of controlled patients (BP<140 and
      <90mmHg) increased from 5.8% to 32.2%. Time between pre- and post-derivation
      visit was 72+/-64days (median 57days, IQ26-99). The PCPH received a medical
      report in 80.3% of cases, 76.9% with an explanation of the results of the
      complementary tests, 75.8% with additional information or a reasoning of
      treatment and in 71% of cases information about the patient future management.
      63% of PCPH were fully agreed with the management of the specialist, 29% agree
      and 2% strongly disagree. The derivation was evaluated as effective or very
      effective in 86% of patients and no effective in 9%. CONCLUSIONS: Communication
      between AE and SC in HTA is valued satisfactorily by MAP. However there is still
      room for improvement in the process.

PMID- 29037789
TI  - Transcranial brain stimulation for the treatment of tinnitus: Positive lessons
      from a negative trial.

PMID- 29037790
TI  - Glucocorticoid receptor in rat nucleus accumbens: Its roles in propofol
      addictions.
AB  - Propofol has been demonstrated as a drug of abuse in humans. Our previous study
      indicated that dexamethasone, a potent agonist of glucocorticoid receptor (GR),
      inhibited propofol-maintained rat self-administration behaviors by systematic
      injection. However, the direct effect of GR in the nucleus accumbens (NAc) on
      propofol self-administration behavior has not been explored. The propofol
      maintained self-administration was established in rats after a successive 3-h
      daily self-administration of propofol for 14days. On day 15, 30min prior to the
      last training, rats received one of three doses (0.3, 1.0, or 3.0MUg/site) of
      dexamethasone or vehicle via intra-NAc injection. The number of active nose-poke
      responses, propofol injections, and inactive nose-poke responses was recorded.
      Dopamine D1 receptor and c-Fos expressions were detected. Plasma corticosterone
      level was measured by enzyme-linked immunosorbent assay. Intra-NAc administration
      of dexamethasone (1.0 and 3.0MUg/site) facilitated the active nose-poke
      responses, which was accompanied by the upregulation of D1 receptor and c-Fos in
      the NAc. Plasma corticosterone level was not changed in dexamethasone-treated
      groups. This study provides crucial evidence that GR in the NAc plays an
      important role in regulating propofol self-administration behaviors in rats,
      which may be mediated by changes in D1 receptor and c-Fos expressions, and this
      also needs further examination with GR antagonist in the future.

PMID- 29037791
TI  - Effect of optogenetic modulation on entopeduncular input affects thalamic
      discharge and behavior in an AAV2-alpha-synuclein-induced hemiparkinson rat
      model.
AB  - OBJECTIVE: Neuromodulation of the globus pallidus internus(GPi) alleviates
      Parkinson's disease symptoms. The primate GPi is homologous to the rat
      entopeduncular nucleus (EP). The aim of the present study was to determine if
      optogenetic modulation of the EP could alter parkinsonian behavior or thalamic
      discharge in a hemiparkinson rat model. METHODS: We injected an adeno-associated
      virus type-2 expressing alpha-synuclein (AAV2-alpha-syn) into the substantia
      nigra pars compacta (SNc) of the right hemisphere and confirmed parkinsonian
      behavior using an amphetamine-induced rotation test. Then we injected activated
      or inhibited neurons, using the channelrhodopsin2 (ChR2)/halorhodopsin (NpHR)
      system in the EP of the hemiparkinson rat model and examined downstream effects
      in vivo. We assessed alterations in parkinsonian behaviors using the stepping and
      cylinder tests before, during, and after optogenetic stimulation. RESULTS:
      Importantly, optogenetic inhibition of the EP improved parkinsonian motor
      behaviors. When we monitored thalamic neuronal activity following optogenetic
      neuromodulation in vivo, and we observed alterations in thalamic discharge The
      thalamic neuronal activity is increased for optogenetic inhibition stimulation,
      whereas decreased for optogenetic activation stimulation. CONCLUSIONS: Taken
      together, our data demonstrate that optical neuromodulation of the EP can
      successfully control contralateral forelimb movement and thalamic discharge in an
      AAV2-alpha-synuclein-induced hemiparkinson rat model.

PMID- 29037792
TI  - Spatial-temporal expression of NDRG2 in brain tissues in a rat model of
      intracerebral hemorrhage: A pilot study.
AB  - N-myc downstream regulated gene 2 (NDRG2) was a member of the N-myc down
      regulated gene family which belongs to the alpha/beta hydrolase superfamily and
      played important roles in cell death. To date, the expression and effects of
      NDRG2 in brain after intracerebral hemorrhage (ICH) are unclear. In this study,
      we investigated the spatial-temporal expression of NDRG2 in brain tissues in a
      rat model of ICH. The expression levels of NDRG2 were tested in 3h, 6h, 12h, 24h,
      48h, 72h, and 7d after ICH by western blot analysis. The results showed that the
      NDRG2 levels were increased and peaked at 24h after ICH, and then declined
      subsequently. Meanwhile, we also examined the NDRG2 cellular localization in
      brain tissues by immunofluorescence analysis with NeuN and GFAP (biomarker of
      neuron and astrocytes respectively). The results demonstrated that NDRG2 was
      mainly expressed in astrocytes, but not neurons, after ICH. Additionally, the
      results of double staining indicated that the rate of NDRG2- and TUNEL -positive
      cells was significantly higher in the brain tissues in rats after ICH. The roles
      of NDRG2 in ICH needed further investigation and inhibiting the expression of
      NDRG2 may have potential therapeutic effects in ICH.

PMID- 29037793
TI  - Transcranial direct current stimulation of the rLPFC shifts normative judgments
      in voluntary cooperation.
AB  - Normative judgment is a key capacity for human social norm compliance. Previous
      studies have revealed that the right lateral prefrontal cortex (rLPFC) is closely
      related to social norm compliance and that it has proven stimulation effects on
      behavior in voluntary and sanction-induced norm compliance, but not normative
      judgments. Nearly all these studies have been based on sanction-induced
      coordination cooperation, and a number of them have found that rLPFC has no
      effect on normative judgment with transcranial direct current stimulation (tDCS).
      However, no research study exists regarding the effects of the normative judgment
      in voluntary cooperation. In this study, we used a linear asymmetric public good
      game to investigate the role of normative judgment in voluntary cooperation with
      tDCS on rLPFC. Participants were engaged in anonymous social interactions and
      made decisions with real financial consequences after being randomly assigned to
      receive either anodal, cathodal, or sham stimulation of 15min. Results suggest
      that compared with the sham group, anodal/cathodal tDCS influenced the behavior
      and normative judgment of participants in opposite directions. These outcomes
      provide a neural evidence for the rLPFC mechanism on normative judgment in
      voluntary cooperation.

PMID- 29037794
TI  - Ventricular Performance is Associated with Need for Extracorporeal Membrane
      Oxygenation in Newborns with Congenital Diaphragmatic Hernia.
AB  - OBJECTIVE: To compare echocardiography (ECHO) findings of patients with
      congenital diaphragmatic hernia (CDH) who required extracorporeal membrane
      oxygenation (ECMO) to non-ECMO treated patients. STUDY DESIGN: We reviewed
      clinical and ECHO data of newborns with CDH born between 2009 and 2016.
      Exclusions included major anomalies, genetic syndromes, or no ECHO prior to ECMO.
      Pulmonary hypertension was assessed by ductal shunting and tricuspid regurgitant
      jet. Speckle tracking echocardiography (STE) assessed function by quantifying
      deformation. RESULTS: Patients with CDH (15 ECMO and 29 with no ECMO) were
      analyzed. Most patients had a left CDH (88.6%). Age at ECHO was similar between
      groups. Outborn status (P = .009) and liver position (P = .009) were associated
      with need for ECMO. Compared with non-ECMO patients, patients who required ECMO
      had significantly decreased left and right ventricular function by both
      conventional and STE measures, as well as decreased right and left ventricular
      output. The right ventricular eccentricity index was higher in ECMO vs non-ECMO
      patients (2.2 vs 1.8, P = .02). There was no difference in pulmonary hypertension
      between CDH groups. CONCLUSIONS: Need for ECMO was associated with decreased left
      and right ventricular function, as assessed by standard and STE measures. There
      was no difference in pulmonary hypertension between non ECMO and ECMO patients.
      Abnormal cardiac function may explain nonresponse to pulmonary vasodilators in
      patients with CDH. Management strategies to improve cardiac function may reduce
      the need for ECMO in newborns with CDH.

PMID- 29037795
TI  - The Burden of Hospital Readmissions among Pediatric Patients with Inflammatory
      Bowel Disease.
AB  - OBJECTIVE: To evaluate the burden and predictors of hospital readmissions among
      pediatric patients with inflammatory bowel disease using the Nationwide
      Readmissions Database. STUDY DESIGN: We performed a retrospective cohort study
      using 2013 Nationwide Readmissions Database. International Classification of
      Diseases, Ninth Revision, Clinical Modification codes were used to identify
      patients <18 years with diagnoses of ulcerative colitis (UC) or Crohn's disease
      (CD). Demographic factors and details of hospitalizations were evaluated using
      survey procedures in SAS v 9.4 (SAS Institute, Cary, North Carolina).
      Multivariable logistic regression was used to estimate ORs and 95% CIs of
      readmission. RESULTS: Among 2733 hospitalizations (63% CD, 37% UC), 611 (22%)
      patients were readmitted within 90 days of the index hospitalization. Readmission
      resulted in weighted estimates of 11 440 excess days of hospitalization and total
      charges of over $107 million. For CD, male sex (aOR 1.36, 95% CI 1.03-1.81) and
      co-existing anxiety or depression (aOR 1.89, 95% CI 1.06-3.40) were associated
      with increased readmissions, while patients who underwent surgery had decreased
      readmissions (aOR 0.40, 95% CI 0.24-0.65). In patients with UC, an index
      admission of >7 days was associated with increased readmissions (aOR 1.69, 95% CI
      1.09-2.62). CONCLUSIONS: Readmission occurs frequently in children with
      inflammatory bowel disease and is associated with significant cost and resource
      burdens. Among patients with CD, psychiatric comorbidities such as anxiety and
      depression are apparent drivers of readmission.

PMID- 29037796
TI  - Salivary Cortisol Levels Predict Therapeutic Response to a Sleep-Promoting Method
      in Children with Postural Tachycardia Syndrome.
AB  - OBJECTIVE: To determine the value of salivary cortisol concentrations in
      predicting the efficacy of sleep-promoting treatment in children with postural
      tachycardia syndrome (POTS). STUDY DESIGN: This prospective study involved 40
      children with POTS and 20 healthy children (controls). POTS was diagnosed using
      the head-up or head-up tilt test. Patients with POTS received a sleep-promoting
      treatment: >8 hours of sleep every night and a midday nap in an appropriate
      environment; no drinking water or exercising before bedtime; and urination before
      bedtime. The Pittsburgh Sleep Quality Index was used to evaluate sleep quality,
      and symptom scores were used to assess POTS severity. Salivary samples were
      collected upon awakening, 30 minutes after awakening, at 12:00 p.m., 4:00 p.m.,
      and 8:00 p.m., and at bedtime before treatment. Enzyme-linked immunosorbent assay
      was used to measure salivary cortisol concentrations. RESULTS: Cortisol
      concentrations were significantly higher in patients with POTS than in the
      controls at all time points (P < .05 for all). PSQI scores were significantly
      higher in patients with POTS (7.2 +/- 3.0) than in the controls (1.35 +/- 1.39; t
      = -10.370, P <.001). Salivary cortisol concentrations at awakening were
      significantly higher in responders than in nonresponders (4.83 +/- 0.73 vs 4.05
      +/- 0.79 ng/mL, t = -3.197, P = .003). The area under the receiver operating
      characteristic curve was 75.8%, (95% CI 59.3%-92%). Cut-off at-awakening salivary
      cortisol concentrations of >4.1 ng/mL yielded 83.3% sensitivity and 68.7%
      specificity in predicting therapeutic efficacy. CONCLUSIONS: At-awakening
      salivary cortisol concentrations may predict the efficacy of sleep-promoting
      treatment in patients with POTS.

PMID- 29037797
TI  - Flow cytometric characterization of encystation in Entamoeba invadens.
AB  - Entamoeba histolytica causes dysentery and liver abscess mostly in countries that
      lack proper sanitation. Infection is acquired by ingestion of the cyst form in
      contaminated food or water. E. histolytica does not encyst in vitro; thus, E.
      invadens, a reptilian parasite that encysts in vitro, has been used as a
      surrogate. Cysts are small and possess chitin-rich walls. These are
      characteristics that may be exploited by flow cytometry. We stained encysting E.
      invadens cells with a fluorescent chitin stain, and analyzed fluorescence and
      forward scatter by flow cytometry. We demonstrate that flow cytometry can be used
      to track differentiation, reveal unique cell populations, and evaluate
      encystation inhibitors.

PMID- 29037798
TI  - Electroencephalographic assessment of oral meloxicam, topical anaesthetic cream
      and cautery iron for mitigating acute pain in pigs (Sus scrofa) undergoing tail
      docking.
AB  - OBJECTIVE: To evaluate the efficacy of oral meloxicam, topical anaesthetic cream
      and cautery iron in mitigating acute nociceptive responses of pigs to tail
      docking. STUDY DESIGN: A prospective, randomized, controlled experimental study.
      ANIMALS: A total of 40 healthy Large WhitexLandrace pigs aged 21+/-1 days,
      weighing 6.1+/-0.9 kg. METHODS: Pigs were randomly assigned to one of four
      treatments (n=10 per treatment): CONTROL: docked using clippers without
      analgesia; MEL: docked using clippers after administration of oral meloxicam;
      EMLA: docked using clippers after application of topical anaesthetic cream; and
      CAUT: docked using a cautery iron without analgesia. Anaesthesia was induced and
      maintained with halothane in oxygen. Following induction, end-tidal halothane was
      stabilized at 0.95-1.05% and electroencephalograph (EEG) recording commenced.
      After 5 minutes of baseline data collection, tail docking was performed and
      recording continued for a further 10 minutes. The EEG summary variables median
      frequency (F50), 95% spectral edge frequency (F95) and total power (PTOT) were
      calculated for the baseline period and for consecutive 30-second intervals
      following docking. RESULTS: Following docking, F50 increased and PTOT decreased
      significantly in CONTROL and MEL pigs. EMLA pigs exhibited no change in any
      variable, whilst CAUT pigs exhibited a reduction in PTOT but no change in F50.
      F50 was higher in control pigs than in EMLA pigs 30-60 seconds after docking
      (p<=0.01). PTOT was lower in CONTROL than in EMLA pigs 30-90 seconds after
      docking (p<0.03) and in CAUT pigs 60 seconds after docking (p=0.01). CONCLUSIONS
      AND CLINICAL RELEVANCE: Prior application of EMLA cream abolished EEG indicators
      of nociception in pigs docked using clippers. Docking using a cautery iron
      without analgesia ameliorated EEG indicators of nociception, relative to using
      clippers without analgesia. Prior administration of EMLA cream or the use of
      cautery instead of clippers may reduce the acute pain experienced by pigs
      undergoing tail docking.

PMID- 29037799
TI  - Thermography as an early predictive measurement for evaluating epidural and
      femoral-sciatic block success in dogs.
AB  - OBJECTIVE: To evaluate skin temperature increase as an early predictive measure
      for evaluating epidural and femoral-sciatic block success in dogs. STUDY DESIGN:
      Prospective clinical trial. ANIMALS: A total of 29 dogs undergoing orthopaedic
      surgery on one hindlimb. METHODS: Dogs were anaesthetized and placed into lateral
      recumbency with the affected limb uppermost and the coat was clipped. Baseline
      infrared thermographic images (T0) of the affected limb, of the paw pad of the
      affected leg and of the ipsilateral paw pad were taken. Subsequently, dogs were
      administered either an epidural (EPI; n=11) or a femoral-sciatic block (FS; n=18)
      using bupivacaine 1 mg kg-1. Then, 2 minutes after placement of the block,
      thermographic images were obtained every 3 minutes for a total of four
      measurements (T1-T4) and surgery was commenced. Rescue analgesia consisting of
      fentanyl 1 MUg kg-1 was administered if needed. A regional block was considered
      successful if the dose of fentanyl administered was less than the lower 95%
      confidence interval of the geometric mean of the total fentanyl used in each
      group. A >= 1  degrees C increase of skin temperature was considered as the
      minimum increase required for detection of a successful block. RESULTS: A total
      of 12 out of 18 blocks in the FS and eight of 11 in the EPI group were considered
      successful based on fentanyl consumption. Out of these, only four of 12 in the FS
      and one of eight in the EPI group developed an increase in temperature of >= 1 
      degrees C. Contrarily, four of six of the nonsuccessful cases in the FS and three
      of three in the EPI group developed an increase in temperature of >= 1  degrees
      C. CONCLUSIONS AND CLINICAL RELEVANCE: Contrary to reports in humans,
      thermography did not indicate regional block success prior to surgery in dogs.
      However further studies under more controlled conditions are needed to determine
      whether thermography can be used to indicate failure of regional blockade.

PMID- 29037800
TI  - Clinical comparison of dexmedetomidine and medetomidine for isoflurane balanced
      anaesthesia in horses.
AB  - OBJECTIVE: To compare the effects of two balanced anaesthetic protocols
      (isoflurane-dexmedetomidine versus medetomidine) on sedation, cardiopulmonary
      function and recovery in horses. STUDY DESIGN: Prospective, blinded, randomized
      clinical study. ANIMALS: Sixty healthy adult warm blood horses undergoing
      elective surgery. METHODS: Thirty horses each were sedated with dexmedetomidine
      3.5 MUg kg-1 (group DEX) or medetomidine 7 MUg kg-1 (group MED) intravenously.
      After assessing and supplementing sedation if necessary, anaesthesia was induced
      with ketamine/diazepam and maintained with isoflurane in oxygen/air and
      dexmedetomidine 1.75 MUg kg-1 hour-1 or medetomidine 3.5 MUg kg-1 hour-1.
      Ringer's lactate (7-10 mL kg-1 hour-1) and dobutamine were administered to
      maintain normotension. Controlled mechanical ventilation maintained end-tidal
      expired carbon dioxide pressures at 40-50 mmHg (5.3-6.7 kPa). Heart rate,
      invasive arterial blood pressure, inspired and expired gas composition and
      arterial blood gases were measured. Dexmedetomidine 1 MUg kg-1 or medetomidine 2
      MUg kg-1 was administered for timed and scored recovery phase. Data were analysed
      using two-way repeated-measures analysis of variance and chi-square test.
      Significance was considered when p<=0.05. RESULTS: In group DEX, significantly
      more horses (n=18) did not fulfil the sedation criteria prior to induction and
      received one or more supplemental doses, whereas in group MED only two horses
      needed one additional bolus. Median (range) total sedation doses were
      dexmedetomidine 4 (4-9) MUg kg-1 or medetomidine 7 (7-9) MUg kg-1. During general
      anaesthesia, cardiopulmonary parameters did not differ significantly between
      groups. Recovery scores in group DEX were significantly better than in group MED.
      CONCLUSIONS AND CLINICAL RELEVANCE: Horses administered dexmedetomidine required
      more than 50% of the medetomidine dose to reach equivalent sedation. During
      isoflurane anaesthesia, cardiopulmonary function was comparable between the two
      groups. Recovery scores following dexmedetomidine were better compared to
      medetomidine.

PMID- 29037801
TI  - Validation of noninvasive blood pressure equipment: which peripheral artery is
      best for comparison studies in dogs?
AB  - OBJECTIVES: 1) To determine which peripheral artery commonly used for invasive
      arterial blood pressure (IBP) monitoring yields the least bias when compared with
      noninvasive blood pressure (NIBP) values obtained at the antebrachium of the dog,
      and 2) to identify and describe differences in systolic (SAP), mean (MAP) and
      diastolic arterial pressures (DAP) among different anatomical locations. STUDY
      DESIGN: Prospective experimental study. ANIMALS: Twenty adult hound dogs weighing
      24.5 +/- 1.1 kg (mean +/- standard deviation). METHODS: Four peripheral arteries
      dorsal pedal, median caudal, intermediate auricular and superficial palmar
      arteries-were catheterized with 20 gauge, 3.8 cm catheters. One NIBP cuff was
      placed in the middle third of the antebrachium. Four sets of IBP and NIBP
      measurements were simultaneously collected every 2 minutes. A linear mixed model
      was performed to analyze the collected data. RESULTS: IBP values varied depending
      on the arterial catheterization site. The difference was greater for SAP. NIBP
      measured at the antebrachium had the best agreement with IBP measured at the
      median caudal artery. CONCLUSION AND CLINICAL RELEVANCE: IBP varies among
      anatomical locations. The smallest bias and narrowest limits of agreement were
      obtained at the median caudal artery, providing the best overall agreement with
      the equipment studied. The median caudal artery may be the preferable anatomical
      location for clinical comparison studies between IBP and NIBP in dogs when the
      cuff is on the antebrachium.

PMID- 29037802
TI  - The impact of inoculum size on the activity of cefoperazone-sulbactam against
      multidrug resistant organisms.
AB  - OBJECTIVES: This study aims to assess the in vitro activity of cefoperazone alone
      and different cefoperazone-sulbactam ratios against different inoculum sizes of
      multidrug resistant organisms. METHODS: Minimum inhibitory concentrations (MICs)
      of cefoperazone, cefoperazone-sulbactam at fixed ratio of 1:1 and 2:1 against a
      normal inoculum size of 5 * 105 CFU/ml and a high inoculum size of 5 * 107 CFU/ml
      were measured. RESULTS: Each 33 isolates of extended-spectrum beta-lactamases
      (ESBL)-producing Escherichia coli, ESBL-producing Klebsiella pneumoniae,
      carbapenem-resistant E. coli, and carbapenem-resistant Pseudomonas aeruginosa and
      a total of 122 isolates of carbapenem-resistant Acinetobacter baumannii were
      collected. After the addition of sulbactam at a 1:1 ratio, most MIC50 and MIC90
      values decreased. Cefoperazone-sulbactam at a 1:1 ratio had a higher
      susceptibility rate against ESBL-producing E. coli, carbapenem-resistant E. coli,
      and carbapenem-resistant A. baumannii than cefoperazone-sulbactam at a 2:1 ratio
      (all P < 0.05). For ESBL-producing E. coli, the susceptibility rate of
      cefoperazone-sulbactam at ratios of (1:1) and (2:1) decreased from 97.0 to 87.9%
      and 90.9 to 60.6%, for normal to high inoculum, respectively. For ESBL-producing
      K. pneumoniae, both susceptibility rate of cefoperazone-sulbactam at ratios of
      (1:1) and (2:1) decreased from 75.8%, and 63.6% at normal inoculum to 51.5% and
      42.4% at high inoculum. CONCLUSIONS: Cefoperazone-sulbactam at a 1:1 ratio has
      greater in vitro activity against most multidrug resistant organisms than
      cefoperazone-sulbactam at a 2:1 ratio. Such combinations were not influenced by
      the inoculum size of ESBL-producing E. coli and K. pneumoniae and could be a
      therapeutic option for treating severe infections.

PMID- 29037803
TI  - Prognostic significance and biopsy characteristics of prostate cancer with
      seminal vesicle invasion on radical prostatectomy: a nationwide population-based
      study.
AB  - The objective of this study was to evaluate the prognostic significance of
      seminal vesicle invasion (SVI, pT3b) compared with extraprostatic extension (EPE)
      alone (pT3a) after radical prostatectomy, and to correlate pre-operative biopsy
      pathology with SVI and EPE. The National Prostate Cancer Register includes all
      prostate cancers diagnosed in Sweden. We analysed 4063 cases with stage category
      pT3a and 1371 cases with pT3b at radical prostatectomy between 2000 and 2012.
      Associations between pT3a and pT3b and progression were evaluated and adjusted
      for year, age, biopsy grade and s-PSA. Needle biopsy findings in these stages
      were compared. Patients with pT3b (n=1371) had a higher risk of death from
      prostate cancer (HR 2.3, 95% CI 1.5-3.3, p<0.001) and death from any cause (HR
      1.5, 95% CI 1.2-1.8, p<0.001) than those with pT3a (n=4063). They were also more
      likely to be treated with post-operative radiotherapy (HR 1.5, 95% CI 1.4-1.7,
      p<0.001) or androgen deprivation therapy (HR 3.0, 95% CI 2.5-3.7, p<0.001),
      indicating clinical progression. Yet, disease-specific survival of patients with
      stage pT3b was 94% after 6 years. Median cancer extent in pre-operative biopsies
      of pT3a and pT3b was 14 and 24 mm (p<0.001), number of positive cores was four
      and five, (p<0.001) and biopsy Gleason score was 8-10 in 11.6% and 27.3%,
      respectively (p<0.001). SVI of prostate cancer is associated with worse outcome
      after radical prostatectomy than EPE alone. However, few patients with SVI die
      within 6 years from surgery, suggesting that radical prostatectomy may be
      curative in locally advanced cancers.

PMID- 29037804
TI  - Fluorescence in situ hybridisation as an ancillary tool in the diagnosis of acral
      melanoma: a review of 44 cases.
AB  - Acral melanoma is associated with outcomes which are more unfavourable than those
      of other melanoma subtypes, and acral melanoma has higher mortality. However,
      histological distinction of acral melanoma from acral naevi may be difficult.
      Fluorescence in situ hybridisation (FISH) targeting specific genes has been used
      as an ancillary method for differential diagnosis of melanocytic tumours, but
      most previous studies have focused on non-acral lesions which may have genetic
      alterations different from acral lesions. We evaluated use of multi-site FISH in
      the diagnosis of acral melanoma in a series of 82 acral melanocytic tumours. Two
      probe groups were applied. Probe set 1 involved a 4-probe FISH targeting 6p25
      (RREB1), CEP6 (centromere 6), 6q23 (MYB) and 11q13 (CCND1). Probe set 2 involved
      a 3-probe FISH targeting 8q24 (MYC), 9p21 (CDKN2A) and CEP9 (centromere 9). In 44
      primary acral melanomas, sensitivity was 70.5% (31/44) using probe set 1 alone,
      and 59.1% (26/44) using probe set 2 alone. When both probe sets were combined,
      sensitivity increased to 88.6% (39/44). The frequency of each gene alteration was
      as follows: MYC gain in 54.5% cases (24/44), RREB1 gain in 52.3% cases (23/44),
      CCND1 gain in 45.4% cases (20/44), MYB loss relative to CEP6 in 25.0% cases
      (11/44), and CDKN2A homozygous deletion in 20.5% cases (9/44). For lesions with
      both in situ and invasive disease, FISH findings in these two components were
      similar. No gene alterations were detected in any of 36 benign acral naevi. In
      this study FISH exhibited sensitivity and specificity in diagnosis of acral
      melanoma which allows its application as an auxiliary diagnostic test in acral
      melanocytic tumours.

PMID- 29037805
TI  - Tolerance and toxicity of the PARP inhibitor olaparib in older women with
      epithelial ovarian cancer.
AB  - OBJECTIVES: The objective of this study was to determine the overall tolerability
      and toxicity of olaparib capsules among older (>=65years) patients with recurrent
      ovarian cancer treated on 8 completed prospective trials of olaparib. METHODS: An
      ancillary data analysis of 398 patients with recurrent ovarian cancer enrolled on
      eight prospective trials of olaparib capsules was performed. Patients aged
      65years and older were stratified into age groups by 5year increments (ages 65
      69, 70-74, >=75years) and compared to those <65. Analysis was restricted to those
      patients receiving the recommended treatment dose of 400mg PO b.i.d. RESULTS: Of
      the 398 patients included, 78 were >=65 (age 65-69 n=38, age 70-74 n=23, age>=75
      n=17). The majority of elderly patients were Caucasian (n=2 Asian) and had
      received >=5 prior lines of chemotherapy. In patients <65, 46.9% required dose
      reduction as compared to 44.7% of patients 65-69years, 47.8% of patients 70
      74years, and 64.7% of patients >=75years (p=0.62). In patients <65years 41.2%
      required dose interruption, as compared to 50%, 43.5%, and 64.7% of patients aged
      65-69, 70-74, and >=75, respectively (p=0.11). There were no occurrences of
      myelodysplastic syndrome or acute myeloid leukemia in any of the older cohorts.
      Toxicities, including grade 3/4 nausea, were similar across age groups.
      CONCLUSIONS: Tolerability and toxicity of olaparib capsules is similar between
      women >=65years and <65years of age treated for advanced recurrent ovarian
      cancer. Use of olaparib should be considered in this patient population.

PMID- 29037806
TI  - PARP inhibitors: Clinical utility and possibilities of overcoming resistance.
AB  - PARP inhibitors represent a major breakthrough in ovarian cancer care. Almost
      half of all ovarian cancers have deficiencies in the homologous recombination
      (HR) DNA repair pathway, namely BRCA1/2 mutations. Given the limited therapeutic
      options for recurrent ovarian cancer patients there has been a significant effort
      to develop novel therapies to exploit DNA repair deficiencies. In 2005 and 2006,
      inhibiting PARP enzymes was first observed to be highly effective against cancers
      with HR deficiencies. PARP inhibitors are being utilized in the clinic to manage
      recurrent ovarian cancers that display defects in the HR repair pathway. However,
      PARP inhibitors also show significant clinical benefit in patients without HR
      deficiencies. There are currently three FDA-approved PARP inhibitors for
      recurrent ovarian cancer and an additional two PARP inhibitors being evaluated in
      late stage clinical trials. Given the expanding clinical use of PARP inhibitors
      and the high likelihood of acquired resistance, there is a significant need for
      clinical strategies to manage PARP inhibitor resistant disease. This review will
      examine PARP inhibitors in the context of: indications and toxicities, novel
      biomarkers to predict response, targeted-therapy resistance, and potential
      approaches to manage resistant disease.

PMID- 29037808
TI  - Application of titration methods for measuring the contents of ammonium nitrogen
      and volatile fatty acids in agricultural biogas plants.
AB  - The aim of our research was to assess a relatively new method of estimating
      ammonium nitrogen concentration in anaerobic digestion of plant substrates. We
      analysed our own data, received from the anaerobic digestion of maize silage
      (PM), as well as data published by Purser et al. (2014) who measured energy crops
      and slurry (ECS), and food waste (FW). In our study, the process was monitored
      for VFA content that was determined by gas chromatography, and for the content of
      ammonium nitrogen determined using the HACH LANGE LCK 303 cuvette test. We
      created polynomial regression models that bind the content of ammonium nitrogen
      with the volume of H2SO4 used to titrate the sample from initial pH to pH 5. To
      estimate parameters of model, the PM dataset was used. The obtained models were
      positively validated using ECS and FW datasets. Our results confirmed the
      effectiveness of the Purser et al. method with an average absolute error of less
      than 223mgl-1 of the VFA concentration, which was approximately 20-times less
      than the level that caused inhibition. In conclusion, we can affirm the
      suitability of using titration methods to assess the ammonium nitrogen content of
      bioreactors with a stable composition.

PMID- 29037807
TI  - DICER1-related Sertoli-Leydig cell tumor and gynandroblastoma: Clinical and
      genetic findings from the International Ovarian and Testicular Stromal Tumor
      Registry.
AB  - BACKGROUND: Ovarian sex cord-stromal tumors (OSCST) include juvenile granulosa
      cell tumors (JGCT), Sertoli-Leydig cell tumor (SLCT) and gynandroblastoma (GAB)
      among others. These ovarian sex cord-stromal tumors as well as other tumors
      including pleuropulmonary blastoma (PPB) may be associated with DICER1 mutations.
      We sought to describe the clinical and genetic findings from the first 107
      individuals enrolled in the International Ovarian and Testicular Stromal Tumor
      Registry. METHODS: Medical and family history were obtained for individuals
      consecutively enrolled in the International Ovarian and Testicular Stromal Tumor
      Registry. Pathology was centrally reviewed. DICER1 sequencing was performed on
      blood and tumor tissue. RESULTS: Of the 107 participants, 49 had SLCT, 25 had
      JGCT and 5 had GAB. Nearly all (36/37) SLCTs and 4/4 GAB tested had a DICER1
      mutation in an RNase IIIb domain hotspot; approximately half of these individuals
      had a predisposing germline DICER1 mutation. Metachronous SLCTs were seen in 3
      individuals with germline DICER1 mutations. Other DICER1-associated conditions
      were seen in 19% of patients with SLCT or GAB. Three children of women with SLCT
      were diagnosed with PPB based on genetic testing and clinical screening during
      the course of this study. All were diagnosed with PPB in its earliest and most
      curable form (Type I), were treated with surgery alone, and are alive without
      evidence of disease. CONCLUSIONS: Recognition of the distinct genetic basis for a
      group of these tumors improves precise classification in difficult cases and
      promotes mutation-based screening and early detection.

PMID- 29037809
TI  - Prognostic significance of high YY1AP1 and PCNA expression in colon
      adenocarcinoma.
AB  - To investigate the relationship between YY1AP1 and various clinicopathological
      features of colon adenocarcinoma (COAD), we conducted immunohistochemical (IHC)
      analyses of human tissue microarrays. We found that YY1AP1 protein expression was
      significantly higher in tumor tissue of the colon and liver, and was
      significantly lower in tumor tissue of the kidney. An analysis that employed the
      SurvExpress database indicated that increased expression of YY1AP1 mRNA was
      significantly associated with the overall survival of COAD patients. To clarify
      the validity of YY1AP1 or PCNA as determined by the IHC analysis was performed on
      59 paired samples from COAD and adjacent normal tissue. Statistically significant
      differences of immunoreactivity for YY1AP1 or PCNA protein expression was
      observed between COAD tissue and adjacent normal tissue. High protein expression
      levels of YY1AP1 and PCNA were also found to be significantly correlated with M
      class and distant metastasis. We also determined that YY1AP1 was correlated with
      PCNA expression in COAD samples, and Kaplan-Meier survival curves indicated that
      YY1AP1 protein expression was significantly associated with poor survival.
      Finally, a univariate analysis demonstrated that YY1AP1 protein expression was
      related to YY1AP1 score, and multivariate analysis revealed that the YY1AP1
      protein expression level was an independent risk factor of overall COAD survival.
      Taken together, our findings indicate that YY1AP1 expression plays an important
      role in the tumorigenesis and progression of COAD and could serve as a clinical
      prognostic indicator for COAD.

PMID- 29037810
TI  - Chemical and thermal sensitivity of medaka TRPA1 analyzed in heterologous
      expression system.
AB  - TRPA1 of insects and several tetrapod vertebrates except for those of rodents
      have been reported to be activated by noxious chemicals and also by high
      temperature with a relatively clear threshold. We previously analyzed the
      characteristics of two TRPA1 paralogs of zebrafish (zTRPA1a, b) and demonstrated
      that zTRPA1a is specialized for chemical sensing while zTRPA1b responds to
      thermal stimulations, that zTRPA1b responds to both cold and heat stimuli, and
      that heat stimulation gradually activates zTRPA1b without a clear threshold. In
      the medaka genome, a single TRPA1 (olTRPA1) gene is present. To examine if
      functional properties of olTRPA1 are similar to TRPA1 of land animals or either
      of zTRPA1a or zTRPA1b, we isolated a TRPA1 cDNA from medaka and performed
      functional analyses. OlTRPA1 showed a sensitivity to four noxious chemicals
      (allyl isothiocyanate, caffeine, carvacrol, methyl anthranilate). We observed
      that cold stimulation does not activate olTRPA1, but heat stimulation gradually
      activates olTRPA1 with an unclear threshold. Results suggested that a single
      TRPA1 functions as a chemical and thermal sensor in medaka, and that a gradual
      heat-activation without clear threshold might be a common feature for TRPA1 of
      fish living in water.

PMID- 29037811
TI  - One-step construction of a molybdenum disulfide/multi-walled carbon
      nanotubes/polypyrrole nanocomposite biosensor for the ex-vivo detection of
      dopamine in mouse brain tissue.
AB  - We developed a new strategy for construction of a biosensor for the
      neurotransmitter dopamine. The biosensor was constructed by one-step
      electrochemical deposition of a nanocomposite in aqueous solution at pH 7.0,
      consisting of molybdenum disulfide, multi-walled carbon nanotubes, and
      polypyrrole. A series of analytical methods was performed to investigate the
      surface characteristics and the improved electrocatalytic effect of the
      nanocomposite, including cyclic voltammetry, electrochemical impedance
      spectroscopy, field-emission scanning electron microscopy, atomic force
      microscopy, and Raman spectroscopy. The constructed biosensor showed high
      sensitivity (1.130 MUAMUM-1cm-2) with a dynamic linearity range of 25-1000 nM and
      a detection limit of 10 nM. Additionally, the designed sensor exhibited strong
      anti-interference ability and satisfactory reproducibility. The practical
      application of the sensor was manifested for the ex vivo determination of
      dopamine neurotransmitters using brain tissue samples of a mouse Parkinson's
      disease model.

PMID- 29037812
TI  - Apolipoprotein A-IV exerts its anorectic action through a PI3K/Akt signaling
      pathway in the hypothalamus.
AB  - Apolipoprotein A-IV (apoA-IV) is a satiation factor that acts in the
      hypothalamus, however, the intracellular mechanisms responsible for this action
      are still largely unknown. Here we report that apoA-IV treatment elicited a rapid
      activation of the phosphatidylinositol-3-kinase (PI3K) signaling pathway in
      cultured primary hypothalamic neurons, and this effect was significantly
      attenuated by pretreatment with LY294002, an inhibitor of the PI3K pathway. To
      determine if the activation of PI3K is required for apoA-IV's inhibitory effect
      on food intake, apoA-IV was administered intracerebroventricularly. We found that
      apoA-IV significantly reduced food intake and activated PI3K signaling in the
      hypothalamus, and these effects were abolished by icv pre-treatment with
      LY294002. To identify the distinct brain sites where apoA-IV exerts its anorectic
      action, apoA-IV was administered into the ventromedial hypothalamus (VMH) through
      implanted bilateral cannula. At a low dose (0.5 MUg), apoA-IV significantly
      inhibited food intake and activated PI3K signaling pathway in the VMH of lean
      rats, but not in high-fat diet-induced obese (DIO) rats. These results
      collectively demonstrate a critical role of the PI3K/Akt pathway in apoA-IV's
      anorectic action in lean rats and suggest a defective PI3K pathway in the VMH is
      responsible for the impaired apoA-IV's anorectic action in the DIO animals.

PMID- 29037813
TI  - Fluorescence-labeled liposome accumulation in injured colon of a mouse model of T
      cell transfer-mediated inflammatory bowel disease.
AB  - Drug delivery systems maximize the efficacy of drugs by improving their
      pharmacokinetic profiles, pharmacodynamic effects, or both and reducing their
      adverse effects. One of the most advanced, clinically available formulations are
      liposome-encapsulated drugs. In this study, we aimed to determine if liposomes
      can selectively deliver compounds in gastrointestinal diseases. Initially, we
      evaluated the correlation between the diarrhea score and accumulation of
      fluorescence (FL)-labeled liposome using in vivo imaging systems in various
      disease states of an inflammatory bowel disease mouse model. The result showed
      that FL-labeled liposome accumulation and colon tissue weight, which reflect the
      disease state were highly and positively correlated. Then, to confirm the
      accumulation of liposomes at injured sites of the colon, we administered both FL
      labeled liposomes and luminescence probes for detecting reactive oxygen species
      (ROS) to the mouse model. The imaging data showed that liposome accumulation
      tended to coincide with ROS detected sites and the correlation coefficient
      indicated a significantly positive correlation between liposome accumulation and
      ROS detection levels. Finally, we evaluated the involvement of macrophages in the
      uptake mechanism of the liposomes by analyzing the relationship between FL
      labeled liposome accumulation and macrophage marker gene expression levels. The
      result showed that the expression of each macrophage marker gene and liposome
      accumulation showed a significant positive correlation. Therefore, the
      macrophages considerably contributed to the uptake mechanism of the liposomes.
      These data suggest that liposomes could be an attractive delivery tool for
      enhancing the accumulation of drug candidates through macrophages in injured
      colonic tissues. This approach is expected to provide new treatment options for
      patients with colitis.

PMID- 29037814
TI  - Piperlongumine suppresses bladder cancer invasion via inhibiting epithelial
      mesenchymal transition and F-actin reorganization.
AB  - Piperlongumine (PL), a natural alkaloid isolated from longer pepper plants, is
      recently found to be a potent selective anti-cancer compound. We first tested its
      anti-cancer effects on bladder cancer, the fifth most common and aggressive
      cancer worldwide, to further explore the therapeutic spectrum and molecular
      mechanisms of PL. PL significantly suppressed bladder cancer cell proliferation,
      the transition of G2/M phase to next phase, migration/invasion in vitro and
      bladder cancer growth/development in vivo. PL markedly elevated reactive oxygen
      species (ROS) and the administration of antioxidants abolished PL induced cell
      proliferation inhibition, G2/M phase arrest and migration suppression on bladder
      cancer cells. In vivo studies demonstrated that PL inhibited epithelial
      mesenchymal transition with profoundly decreased level of Slug, beta-catenin,
      ZEB1 and N-Cadherin. Further, we first reported PL effects on cytoskeleton with
      prominently reduced lamellipodia formation and decreased F-actin intensity in
      bladder cancer cells. Taken together, our results first revealed that PL
      suppressed bladder cancer proliferation and migration in vivo and in vitro,
      suggesting novel mechanism underlying PL's anti-cancer effect and providing a new
      anticancer drug strategy for bladder cancer therapy.

PMID- 29037815
TI  - An operating principle of the turtle utricle to detect wide dynamic range.
AB  - The utricle encodes both static information such as head orientation, and dynamic
      information such as vibrations. It is not well understood how the utricle can
      encode both static and dynamic information for a wide dynamic range (from <0.05
      to >2 times the gravitational acceleration; from DC to > 1000 Hz vibrations).
      Using computational models of the hair cells in the turtle utricle, this study
      presents an explanation on how the turtle utricle encodes stimulations over such
      a wide dynamic range. Two hair bundles were modeled using the finite element
      method-one representing the striolar hair cell (Cell S), and the other
      representing the medial extrastriolar hair cell (Cell E). A mechano-transduction
      (MET) channel model was incorporated to compute MET current (iMET) due to hair
      bundle deflection. A macro-mechanical model of the utricle was used to compute
      otoconial motions from head accelerations (aHead). According to known anatomical
      data, Cell E has a long kinocilium that is embedded into the stiff otoconial
      layer. Unlike Cell E, the hair bundle of Cell S falls short of the otoconial
      layer. Considering such difference in the mechanical connectivity between the
      hair cell bundle and the otoconial layer, three cases were simulated: Cell E
      displacement-clamped, Cell S viscously-coupled, and Cell S displacement-clamped.
      Head accelerations at different amplitude levels and different frequencies were
      simulated for the three cases. When a realistic head motion was simulated, Cell E
      was responsive to head orientation, while the viscously-coupled Cell S was
      responsive to fast head motion imitating the feeding strike of a turtle.

PMID- 29037817
TI  - Reconstruction method for extended depth-of-field optical diffraction tomography.
AB  - In the paper we present a novel method of extended depth-of-field limited-angle
      optical diffraction tomography, in which the change of a focal plane position is
      performed with a liquid focus-tunable lens. One sinogram is acquired for each
      state of a focus-tunable lens. After acquisition process is complete, all
      sinograms are independently reconstructed and stitched to form the final
      tomographic reconstruction. The presented solution effectively extends the
      applicability of the Rytov approximation to relatively thick samples and provides
      uniform resolution of 3D tomographic reconstructions. The method is also combined
      with Generalized Total Variation Iterative Constraint algorithm, which minimizes
      distortion of the results due to the limited angular range of acquired
      projections. The combined solution is dedicated to investigation of transparent
      and semi-transparent biological micro-structures, like cells and tissue slices.

PMID- 29037816
TI  - In vitro segregation and isolation of human pluripotent stem cell-derived neural
      crest cells.
AB  - The neural crest (NC) is a transient embryonic cell population with remarkable
      characteristics. After delaminating from the neural tube, NC cells (NCCs) migrate
      extensively, populate nearly every tissue of the body and differentiate into
      highly diverse cell types such as peripheral neurons and glia, but also
      mesenchymal cells including chondrocytes, osteocytes, and adipocytes. While the
      NC has been extensively studied in several animal models, little is known about
      human NC development. A number of methods have been established to derive NCCs in
      vitro from human pluripotent stem cells (hPSC). Typically, these protocols
      comprise several cell culture steps to enrich for NCCs in the neural derivatives
      of the differentiating hPSCs. Here we report on a remarkable and hitherto
      unnoticed in vitro segregation phenomenon that enables direct extraction of
      virtually pure NCCs during the earliest stages of hPSC differentiation. Upon
      aggregation to embryoid bodies (EB) and replating, differentiating hPSCs give
      rise to a population of NCCs, which spontaneously segregate from the EB outgrowth
      to form conspicuous, macroscopically visible atoll-shaped clusters in the
      periphery of the EB outgrowth. Isolation of these NC clusters yields
      p75NTR(+)/SOXE(+) NCCs, which differentiate to peripheral neurons and glia as
      well as mesenchymal derivatives. Our data indicate that differentiating hPSC
      cultures recapitulate, in a simplified manner, the physical segregation of
      central nervous system (CNS) tissue and NCCs. This phenomenon may be exploited
      for NCC purification and for studying segregation and differentiation processes
      observed during early human NC development in vitro.

PMID- 29037818
TI  - snRNP proteins in health and disease.
AB  - Split gene architecture of most human genes requires removal of intervening
      sequences by mRNA splicing that occurs on large multiprotein complexes called
      spliceosomes. Mutations compromising several spliceosomal components have been
      recorded in degenerative syndromes and haematological neoplasia, thereby
      highlighting the importance of accurate splicing execution in homeostasis of
      assorted adult tissues. Moreover, insufficient splicing underlies defective
      development of craniofacial skeleton and upper extremities. This review
      summarizes recent advances in the understanding of splicing factor function
      deduced from cryo-EM structures. We combine these data with the characterization
      of splicing factors implicated in hereditary or somatic disorders, with a focus
      on potential functional consequences the mutations may elicit in spliceosome
      assembly and/or performance. Given aberrant splicing or perturbations in splicing
      efficiency substantially underpin disease pathogenesis, profound understanding of
      the mis-splicing principles may open new therapeutic vistas. In three major
      sections dedicated to retinal dystrophies, hereditary acrofacial syndromes, and
      haematological malignancies, we delineate the noticeable variety of conditions
      associated with dysfunctional splicing and accentuate recurrent patterns in
      splicing defects.

PMID- 29037820
TI  - Fetal intervention: Improving evidence and expanding applications.

PMID- 29037819
TI  - Drug-Induced Paradoxical Vocal Fold Motion.
AB  - Vocal cord dysfunction, also known as paradoxical vocal fold motion (PVFM), is a
      disorder characterized by abnormal vocal cord adduction during inspiration. PVFM
      is commonly misdiagnosed as asthma because of the similarity of symptoms: cough,
      wheezing, chest pain, and dyspnea. We present the clinical vignette of a 36-year
      old woman with juvenile rheumatoid arthritis and multiple adverse drug reactions
      who presented with recurrent episodes of unrecognized PVFM during skin testing
      for drug allergy, omalizumab treatment, and tocilizumab desensitization. Before
      the diagnosis of PVFM, these episodes were treated as anaphylaxis, including the
      administration of epinephrine. Once diagnosed and treated for PVFM, the patient
      did not present any further events and continued treatment for drug allergy. PVFM
      may be underreported in hypersensitivity reactions because of the similarity to
      Type 1-mediated respiratory symptoms and comorbid asthma.

PMID- 29037821
TI  - Validation of a Novel Inverted Peg Transfer Task: Advancing Beyond the Regular
      Peg Transfer Task for Surgical Simulation-Based Assessment.
AB  - OBJECTIVE: To evaluate the validity of a novel inverted peg transfer (iPT) task
      for assessing laparoscopic skills of novices and experts and compare iPT to the
      regular PT (rPT) task to ensure surgical trainee acquisition of an adequate
      advanced laparoscopic skills level for safe laparoscopic practice in the
      operating room. DESIGN: Prospective crossover study. SETTING: Multidisciplinary
      simulation center and motion analysis laboratory, Mayo Clinic. PARTICIPANTS:
      Novices were medical students and surgical interns without laparoscopic
      experience. Experts were surgeons with at least 3 years of experience in
      laparoscopic surgery. METHODS: This was the first exposure to iPT for both
      groups. Completion time and performance metrics were recorded. A scoring rubric
      was used to calculate a normalized performance score between 0 and 100. Wilcoxon
      rank sum and Mann-Whitney tests were performed with alpha = 0.05. Receiver
      operating characteristic curves were graphed for the 2 task scores to assess the
      tasks' sensitivity and specificity in differentiating laparoscopic experience
      level. MAIN OUTCOME MEASURES: Performance measures of completion time,
      transferred triangles, dropped triangles (errors), and the overall performance
      score on both tasks between- and within-subjects (i.e., novices and experts).
      RESULTS: Thirty-six novices and eight experts participated. Both experts and
      novices had longer completion time and lower scores during iPT than rPT (p <
      0.05). Within iPT, novice completion times were 144 seconds longer (p = 0.04),
      and performance score was 35 points lower than experts (p < 0.01). No differences
      between novices and experts were observed for completion time or performance
      scores (p > 0.05) for rPT. The iPT scores had a higher sensitivity and
      specificity than the rPT (area under the receiver-operating characteristic curve:
      iPT = 0.91; rPT = 0.69). CONCLUSIONS: iPT is a valid assessment of advanced
      laparoscopic skills for surgical trainees with higher specificity and sensitivity
      than rPT. As advanced minimally invasive surgery becomes more common, it is
      important that tasks such as iPT be included in surgical simulation curricula and
      training assessment.

PMID- 29037822
TI  - How Does Level and Type of Experience Affect Measurement of Joint Range of
      Motion?
AB  - OBJECTIVES: Comparison of range of motion measurements by 3 types of
      investigators with different levels and types of training using three different
      measurement techniques. The study hypothesis was that the accuracy and precision
      of range of motion measurements would vary based on (1) the level and type of
      experience of the investigator and (2) the measurement technique used.
      DESIGN/SETTING: Descriptive laboratory study. PARTICIPANTS: Ten fresh frozen
      cadavers (20 upper and 20 lower extremities). INTERVENTIONS: Shoulder, elbow,
      hip, and knee motion were measured using 3 different measurement techniques
      (digital photography, goniometry, and visual estimation) by 3 groups of
      investigators (attending orthopedic surgeons, physical therapists, and
      residents). Accuracy was defined by the difference from the reference standard
      (motion capture analysis), whereas precision was defined by the proportion of
      measurements within either 5 degrees  or 10 degrees  of the reference standard.
      Analysis of variance, t-tests, and chi-squared tests were used. RESULTS:
      Statistically significant (p < 0.05) differences in accuracy were found for hip
      flexion, abduction, internal rotation, external rotation, and knee flexion.
      However, none of these differences met the authors' defined clinical significance
      (maximum difference 3 degrees ). Precision was significantly (p < 0.05) different
      for elbow extension, hip flexion, abduction, internal rotation, external
      rotation, and knee flexion. CONCLUSION: This study found that clinically accurate
      measurements of shoulder, elbow, hip, and knee motion are obtained regardless of
      technique used or the investigators' level and type of experience. Precision was
      equivalent for all shoulder motions, elbow flexion, and knee extension, but
      varied by as much as 7% to 28% between groups for all other motions.

PMID- 29037823
TI  - The Development of a Novel Perfused Cadaver Model With Dynamic Vital Sign
      Regulation and Real-World Scenarios to Teach Surgical Skills and Error
      Management.
AB  - The landscape of graduate medical education has changed dramatically over the
      past decade and the traditional apprenticeship model has undergone scrutiny and
      modifications. The mandate of the 80-hour work-week, the introduction of
      integrated residency programs, increased global awareness about patient safety
      along with financial constraints have spurred changes in graduate educational
      practices. In addition, new technologies, more complex procedures, and a host of
      external constraints have changed where and how we teach technical and procedural
      skills. Simulation-based training has been embraced by the surgical community and
      has quickly become an essential component of most residency programs as a method
      to add efficacy to the traditional learning model. The purpose of this paper is
      twofold: (1) to describe the development of a perfused cadaver model with dynamic
      vital sign regulation, and (2) to assess the impact of a curriculum using this
      model and real world scenarios to teach surgical skills and error management. By
      providing a realistic training environment our aim is to enhance the acquisition
      of surgical skills and provide a more thorough assessment of resident
      performance. Twenty-six learners participated in the scenarios. Qualitative data
      showed that participants felt that the simulation model was realistic, and that
      participating in the scenarios helped them gain new knowledge, learn new surgical
      techniques and increase their confidence performing the skill in a clinical
      setting. Identifying the importance of both technical and nontechnical skills in
      surgical education has hastened the need for more realistic simulators and
      environments in which they are placed. Team members should be able to interact in
      ways that allow for a global display of their skills thus helping to provide a
      more comprehensive assessment by faculty and learners.

PMID- 29037824
TI  - Resource Usage Implementing the Surgical Resident Prep Curriculum at a Single
      Institution.
AB  - OBJECTIVE: The Resident Prep Curriculum (RPC), published in 2014 and developed as
      a collaboration of the American College of Surgeons, Association of Program
      Directors in Surgery, and the Association for Surgical Education, was designed to
      improve the quality and consistency of medical student preparation for surgical
      residency. We aim to assess the feasibility of and resource usage for
      implementation of this curriculum at our institution. DESIGN: Our institution
      expanded upon a pre-existing 2-week surgical preparatory course, adding modules
      designed to meet the goals and objectives of the RPC. We performed an evaluation
      of the resources required for these additions, namely time, logistics and
      incremental cost. SETTING: The course took place at the Perelman School of
      Medicine, which is a large, academic medical center affiliated with the Hospital
      of the University of Pennsylvania. RESULTS: Our course satisfied each of the six
      domains outlined in the RPC. In 2015, 22 students were enrolled in the course. It
      was run over a consecutive 4-week period in the spring of 2015, with 9 full and 9
      half days. To meet the needs of the Curriculum, approximately 33 hours (38%) were
      spent in the classroom, 34 hours (39%) in a simulation center, and 20 hours (23%)
      in the anatomical laboratory. Seventy faculty-hours (from 5 disciplines) and 73
      resident-hours (double-counting for cotaught modules) were required to support
      the course. Besides room availability, funding was required for certain aspects
      of the course such as cadavers, dedicated anatomy teaching, and the costs of
      supplies in the simulation center. There is also a cost associated with the use
      of the Penn Medicine Simulation Center. Taking these into account, the total cost
      of implementing the curriculum amounted to $30,627.10. CONCLUSION: The
      implementation of the RPC was feasible but relied heavily upon faculty/resident
      time. As a result of the success of this initiative, our medical school seeks to
      expand the idea across multiple specialties.

PMID- 29037825
TI  - Vitamin D prevents lipid accumulation in murine muscle through regulation of
      PPARgamma and perilipin-2 expression.
AB  - Vitamin D plays an important role in regulation of skeletal muscle tone and
      contraction. Serum vitamin D status is linked to muscle power and force in
      adolescent girls, and vitamin D deficiency is associated with myopathies in
      children and poorer physical performance in the elderly. We previously reported
      that vitamin D deficiency is linked to a significant increase in muscle fatty
      infiltration in healthy young women, and studies in patients with neuromuscular
      disorders also associate muscle weakening and lipid content. In order to better
      understand the link between vitamin D status and skeletal muscle lipid
      metabolism, we compared the effect of a low (25IU/kg) or normal (1000IU/kg)
      vitamin D3 diet on muscle fat in female FVB mice maintained in a room without UVB
      lighting to minimize endogenous vitamin D production. Animals on low vitamin D
      diet displayed lower circulating 25(OH)D levels and a dramatic increase (287+/
      52% compared to normal diet, p<0.0001) in lipid deposition in skeletal muscle
      accompanied by muscle fiber disorganization. Lipid droplet staining increased by
      242+/-23% (p<0.0001) in low vitamin D diet, and lipid droplet coat protein
      perilipin-2 and nuclear receptor transcription factor PPARgamma expression levels
      were increased compared to mice fed the normal vitamin D diet: average staining
      for PLIN2: 0.22+/-0.08 (25IU/kg diet) vs 0.10+/-0.02 (1000IU/kg). Average
      staining for PPARgamma: 0.24+/-0.06 (25IU/kg diet) vs 0.07+/-0.04 (1000IU/kg)
      p<0.0001. Tissue mass spectrometry imaging revealed major differences in muscle
      phospholipids profile depending on diet. In vitro, 1,25(OH)2D3 treatment of 3T3
      L1 pre-adipocytes inhibited appearance of lipid droplets by 79+/-9.3%, and caused
      a 80+/-10% and 25+/-8% (p=0.001) reduction in PPARgamma and perilipin-2 mRNA
      levels (by qPCR) compared to control cells. In summary, we report here the first
      in vivo model illustrating the important structural muscle fiber disorganization
      and fat accumulation inside and outside muscle fibers that accompany vitamin D
      deficiency. Furthermore, we show that the underlying mechanisms involve PPARgamma
      and perilipin-2.

PMID- 29037826
TI  - Occurrence of four Anaplasma species with veterinary and public health
      significance in sheep, northwestern China.
AB  - The members of the genus Anaplasma are important tick-borne rickettsial bacteria
      of veterinary and public health significance. Domestic ruminants are important
      reservoir hosts for several Anaplasma species. In this study, the occurrence of
      Anaplasma spp. was investigated by PCR in domestic small ruminants from Gansu,
      northwestern China. The results showed a high prevalence of Anaplasma spp.
      (46.2%, 201/435) in sheep. The average infection rates were 5.7%, 24.4%, 28.0%
      and 18.2% for A. ovis, A. bovis, A. phagocytophilum and A. capra, respectively.
      Coinfection of different Anaplasma species occurred in 96 (22.1%) sheep. The
      infections of Anaplasma species in sheep were confirmed by sequencing of msp4,
      16S rRNA and gltA genes. Sequence analysis revealed a novel A. capra genotype in
      sheep that was distinct from the isolates identified from patients in
      northeastern China. This study gives the first insight of presence of four
      distinct Anaplasma species with veterinary and medical significance in sheep in
      northwestern China.

PMID- 29037827
TI  - Improvement of serum lipids concentration in a general population historical
      cohort. Why?
AB  - BACKGROUND: Knowledge about the harmful effects of high levels of low-density
      lipoprotein cholesterol (cLDL) in adults increased after the publication of
      various guidelines, leading to closer control and more treatment. We hypothesized
      that these health care changes would result in an overall improvement in the
      lipid profile of the population. OBJECTIVE: To determine the evolution of the
      lipid profile in the population of Spain from the Diet and Risk of Cardiovascular
      Disease in Spain cohort. METHODS: A comparison was made between the baseline
      population-based probabilistically sampled DRECE cohort (DRECE 1 study, 1992
      1994, n=4787) and its 13 years later revisit (DRECE 3 study, 2005-2007). A cross
      sectional comparison was made of the overall population of DRECE1 and DRECE3,
      including only individuals aged 20 to 60 years (inter-individual variations). For
      subjects participating in both DRECE1 and DRECE3 (n=1039), individual variations
      over time (intra-individual analyses) were examined. RESULTS: In the overall
      population, the prevalence of lipid-lowering therapy increased from 3.8% in
      DRECE1 to 10.7% in DRECE3. Comparing the lipid profile of the population aged 20
      60 years in DRECE1 with the same age group in DRECE3, an overall decrease is
      observed in total cholesterol from a mean of 203.31mg/dl (SD 43.51) in 1992-1994
      to 196.31mg/dl (SD 38.53) in 2005-2007, and in cLDL from a mean of 125.78mg/dl
      (SD 38.53) to 121.37mg/dl (SD 34.22). The proportion of the population with total
      cholesterol >200mg/dl decreased from 51% in DRECE1 to 47% in DRECE3, although
      this difference did not reach statistical significance (p=0.077). As regards the
      intra-individual analyses, total cholesterol increased from DRECE1 to DRECE3 in
      men and women younger than 40 years at baseline, but decreased in those who were
      older. Index of individuality for total cholesterol, cLDL, cHDL and triglycerides
      ranged from 0.53 to 0.87. CONCLUSIONS: The lipid profile of the Spanish
      population improved between 1992-1994 and 2005-2007. Within individuals, lipid
      concentrations, especially total cholesterol and cLDL have increased, although
      the trend is favorable in the middle-age group (40-59 years). These changes seem
      to be due to several causes, impacted by dietary and lifestyle factors, and also
      by a greater emphasis in lipid-lowering therapy in middle-aged people. Lipid
      parameters had a low index of individuality, which limits their usefulness as
      population reference values.

PMID- 29037829
TI  - Foreword-Pediatric Environmental Health: Using Data on Toxic Chemical Emissions
      in Practice.

PMID- 29037828
TI  - Chemogenetic modulation of cholinergic interneurons reveals their regulating role
      on the direct and indirect output pathways from the striatum.
AB  - The intricate balance between dopaminergic and cholinergic neurotransmission in
      the striatum has been thoroughly difficult to characterize. It was initially
      described as a seesaw with a competing function of dopamine versus acetylcholine.
      Recent technical advances however, have brought this view into question
      suggesting that the two systems work rather in concert with the cholinergic
      interneurons (ChIs) driving dopamine release. In this study, we have utilized two
      transgenic Cre-driver rat lines, a choline acetyl transferase ChAT-Cre transgenic
      rat and a novel double-transgenic tyrosine hydroxylase TH-Cre/ChAT-Cre rat to
      further elucidate the role of striatal ChIs in normal motor function and in
      Parkinson's disease. Here we show that selective and reversible activation of
      ChIs using chemogenetic (DREADD) receptors increases locomotor function in intact
      rats and potentiate the therapeutic effect of L-DOPA in the rats with lesions of
      the nigral dopamine system. However, the potentiation of the L-DOPA effect is
      accompanied by an aggravation of L-DOPA induced dyskinesias (LIDs). These LIDs
      appear to be driven primarily through the indirect striato-pallidal pathway since
      the same effect can be induced by the D2 agonist Quinpirole. Taken together, the
      results highlight the intricate regulation of balance between the two output
      pathways from the striatum orchestrated by the ChIs.

PMID- 29037830
TI  - Obesity and hypertension in children -a growing problem.

PMID- 29037831
TI  - A complex case of pacemaker lead endocarditis.
AB  - Pacemaker lead endocarditis is an uncommon complication after pacemaker
      implantation, but is associated with high rates of morbidity and mortality. The
      authors describe the case of a 68-year-old woman with a double-chamber pacemaker
      since 2007, admitted to an internal medicine department for spondylodiscitis and
      Staphylococcus aureus bacteremia. During hospitalization, she had an episode of
      syncope; the 12-lead electrocardiogram showed pacemaker malfunction with
      ventricular undersensing and loss of capture. A transesophageal echocardiogram
      showed images compatible with vegetations on the pacemaker leads. After
      antimicrobial therapy, the patient developed acute renal failure with subsequent
      multiple organ failure and death. A high index of clinical suspicion is required
      for early diagnosis and appropriate treatment of cardiac device-related infective
      endocarditis.

PMID- 29037832
TI  - Resynchronization therapy in patients with atrial fibrillation: What are the
      results?

PMID- 29037833
TI  - Insights into the background of autonomic medicine.
AB  - Knowledge of the physiology underlying the autonomic nervous system is pivotal
      for understanding autonomic dysfunction in clinical practice. Autonomic
      dysfunction may result from primary modifications of the autonomic nervous system
      or be secondary to a wide range of diseases that cause severe morbidity and
      mortality. Together with a detailed history and physical examination, laboratory
      assessment of autonomic function is essential for the analysis of various
      clinical conditions and the establishment of effective, personalized and precise
      therapeutic schemes. This review summarizes the main aspects of autonomic
      medicine that constitute the background of cardiovascular autonomic dysfunction.

PMID- 29037834
TI  - Microvascular reperfusion in myocardial infarction: The new concept of the open
      artery in the 21st century.

PMID- 29037835
TI  - Pulmonary arteriovenous malformation closure in a preterm newborn.

PMID- 29037836
TI  - The genomic and transcriptomic basis of the potential of Lactobacillus plantarum
      A6 to improve the nutritional quality of a cereal based fermented food.
AB  - The objective of this work was to investigate the nutritional potential of
      Lactobacillus plantarum A6 in a food matrix using next generation sequencing. To
      this end, we characterized the genome of the A6 strain for a complete overview of
      its potential. We then compared its transcriptome when grown in a food matrix
      made from pearl millet to and its transcriptome when cultivated in a laboratory
      medium. Genomic comparison of the strain L. plantarum A6 with the strains WCFS1,
      ST-III, JDM1 and ATCC14917 led to the identification of five regions of genomic
      plasticity. More specifically, 362 coding sequences, mostly annotated as coding
      for proteins of unknown functions, were specific to L. plantarum A6. A total of
      1201 genes were significantly differentially expressed in laboratory medium and
      food matrix. Among them, 821 genes were up-regulated in the food matrix compared
      to the laboratory medium, representing 23% of whole genomic objects. In the
      laboratory medium, the expression of 380 genes, representing 11% of the all
      genomic objects was at least double than in the food matrix. Genes encoding
      important functions for the nutritional quality of the food were identified.
      Considering its efficiency as an amylolytic strain, we investigated all genes
      involved in carbohydrate metabolism, paying particular attention to starch
      metabolism. An extracellular alpha amylase, a neopullulanase and maltodextrin
      transporters were identified, all of which were highly expressed in the food
      matrix. In addition, genes involved in alpha-galactoside metabolism were
      identified but only two of them were induced in food matrix than in laboratory
      medium. This may be because alpha galactosides were already eliminated during
      soaking. Different biosynthetic pathways involved in the synthesis of vitamin B
      (folate, riboflavin, and cobalamin) were identified. They allowed the
      identification of a potential of vitamin synthesis, which should be confirmed
      through biochemical analysis in further work. Surprisingly, some genes involved
      in metabolism and bioaccessibility of iron were identified. They were related
      directly to the use of transport of iron, or indirectly to metabolism of
      polyphenols, responsible of iron chelation in the food. The combination of
      genomics and transcriptomics not only revealed previously undocumented
      nutritional properties of L. plantarum A6, but also documented the behaviour of
      this bacterium in food.

PMID- 29037837
TI  - The correlation between XIAP gene polymorphisms and esophageal squamous cell
      carcinoma susceptibility and prognosis in a Chinese population.
AB  - OBJECTIVE: This study aims to explore the correlation between X-linked inhibitor
      of apoptosis protein (XIAP) gene polymorphisms (rs8371 and rs9856) with the
      susceptibility and prognosis of esophageal squamous cell carcinoma (ESCC),
      providing a potential treatment for ESCC. METHOD: A total of 170 ESCC patients
      (case group) and 191 healthy people (control group) were enrolled in our study.
      Genotyping was conducted on the basis of the ligase detection reaction (LDR). The
      expressions of XIAP polymorphisms were detected. The patients were followed up
      every three months until death or the last follow-up day. The overall survival
      (OS) and progression free survival (PFS) were recorded by Kaplan-Meier survival
      curve, and the relationship between XIAP gene polymorphism and risk and prognosis
      of ESCC was assessed by Cox multivariate analysis. RESULT: TT+CT genotype and T
      allele frequencies of XIAP rs8371 and rs9856 in the case group were significantly
      lower compared to those of the control group (all P<0.05), suggesting that TT+CT
      genotype of XIAP rs8371 and rs9856 was associated with ESCC susceptibility. XIAP
      rs8371 and rs9856 polymorphisms were associated with tumor node metastasis (TNM)
      staging, depth of invasion and lymph node metastasis. The OS and PFS of TT+CT
      genotype carriers of rs8371 were longer than those of CC genotype carriers.
      Smoking, alcohol, TNM staging, depth of invasion, and lymph node metastasis were
      significantly associated with the OS and PFS in ESCC patients. Higher TNM
      staging, depth of invasion, and presence of lymph node metastasis were
      independent risk factors, while XIAP rs8371 was an independent protective factor
      for the prognosis of ESCC patients. CONCLUSION: The present study demonstrates
      that XIAP rs8371 and rs9856 are associated with susceptibility to ESCC, and
      rs8371 polymorphisms might serve as an indicator for improved clinical efficacy
      and prognosis of ESCC patients.

PMID- 29037838
TI  - Expression and epigenetic regulation of cystatin B in lung cancer and colorectal
      cancer.
AB  - AIMS: Dysregulated expression of cystatin B (CSTB) has been implicated in various
      cancers. The aims of this study were to analyze the CSTB expression and
      investigate the epigenetic regulation of CSTB in lung and colon cancer cell
      lines, and also evaluate the clinical outcome of CSTB in primary lung and
      colorectal tumors. METHODS: CSTB expression in lung and colon cancer cell lines
      was analyzed by real-time RT-PCR and western blotting. Epigenetic regulation of
      CSTB was examined by demethylation, deacetylation tests and bisulfite sequencing
      (BS). In primary lung and colorectal tumors, the protein expression of CSTB was
      evaluated by immunohistochemistry on tissue microarray. RESULTS: CSTB was
      downregulated in lung cancer cell lines on mRNA and protein levels compared to
      human bronchial epithelial cells (HBEC). In colon cancer cell lines, CSTB was
      weakly expressed in Caco2, CX2 and HCT-16 and highly expressed in HT-29, WiDr,
      SW480 and HRT-18 on mRNA level compared to normal colonic fibroblast cells
      CCD33Co. After treatment with demethylation agent 5-aza-2'-deoxycytidine,
      increased CSTB mRNA expression was found in 7 out of 11 lung cancer cell lines
      including H226, H157, H2170, H1299, COLO677, A549 and H1975, while no obvious
      alteration was found in colon cancer cell lines. No DNA methylation could be
      found in the selected CpG islands in two types of cancer cell lines by bisulfite
      sequencing. In primary tumors, CSTB expression was significantly and inversely
      correlated with lung tumor stage (pN) and tumor grade (p=0.022 and 0.047,
      respectively). Kaplan-Meier survival curve revealed a tendency that lung tumors
      with high CSTB expression had a more favourable prognosis (p=0.062). In
      colorectal tumors, CSTB was not linked to any clinicopathological parameters
      including age, size of tumor, lymph node metastasis and tumor grading.
      CONCLUSIONS: CSTB might be a potential prognostic marker for patients with
      primary lung cancer.

PMID- 29037839
TI  - Upregulation of caprin1 expression is associated with poor prognosis in
      hepatocellular carcinoma.
AB  - Caprin-1 has been found to promotes osteosarcoma tumor growth, lung metastasis in
      mice, regulating the proliferation and invasion of human breast cancer cells and
      up-regulated in proton beam irradiated human melanoma cells. However, its
      clinical role, biological function in the hepatocellular carcinoma (HCC) remains
      unknown. In the present study, we investigated the clinical significance of
      Caprin1 in the HCC. Caprin1 expression was detected by immunohistochemistry, and
      the expression level was analyzed in 65 HCC tissues and paired peritumoral
      tissue. Prognostic value of Caprin1 in HCC was evaluated in 174 cases using
      Kaplan-Meier analysis. Univariate survival analysis and multiple Cox proportional
      hazards regression were performed using the Cox regression analysis.
      Immunohistochemistry revealed that Caprin1 expression in 65 HCC tissues was
      upregulated compared to paired peritumoral tissue (p=0.0064). Survival analysis
      in 174 HCC patient tissues was showed that high Caprin1 expression was
      significantly associated with worse overall survival (HR=1.513, p=0.042). In
      conclusion, high Caprin1 expression independently predicts a poor outcome for
      patients with HCC, supporting that Caprin1 may be a promising novel HCC
      prognostic factor.

PMID- 29037840
TI  - Comparison of plasma copeptin and multiple biomarkers for assessing prognosis of
      patients with aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Increased plasma copeptin concentrations are related to poor
      prognosis after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study
      was to assess prognostic significance of plasma copeptin detection compared with
      glial fibrillary astrocyte protein, myelin basic protein, S100B, phosphorylated
      axonal neurofilament subunit H, neuron-specific enolase, tau and ubiquitin
      carboxyl-terminal hydrolase L1 in aSAH. METHODS: We detected plasma
      concentrations of the aforementioned biomarkers in 105 healthy controls using
      ELISA. Their predictive ability for symptomatic cerebral vasospasm and 6-month
      poor outcome (Glasgow Outcome Scale score of 1-3) were compared. RESULTS: Plasma
      concentrations of the preceding biomarkers were highly correlated with World
      Federation of Neurological Surgeons subarachnoid hemorrhage scale (WFNS) scores
      as well as were significantly higher in patients with symptomatic cerebral
      vasospasm than in those without symptomatic cerebral vasospasm and in patients
      with poor outcome than in those with good outcome. In terms of area under
      receiver operating characteristic curve, their predictive value for symptomatic
      cerebral vasospasm and 6-month poor outcome was in the range of WFNS scores.
      Plasma copeptin concentration, but not plasma concentrations of other biomarkers,
      statistically significantly improved the predictive performance of WFNS scores.
      CONCLUSIONS: Copeptin in plasma might have the potential to be a useful
      prognostic biomarker for aSAH.

PMID- 29037841
TI  - First report on an X-linked hypohidrotic ectodermal dysplasia family with X
      chromosome inversion: Breakpoint mapping reveals the pathogenic mechanism and
      preimplantation genetics diagnosis achieves an unaffected birth.
AB  - BACKGROUND: To investigate the etiology of X-linked hypohidrotic ectodermal
      dysplasia (XLHED) in a family with an inversion of the X chromosome
      [inv(X)(p21q13)] and to achieve a healthy birth following preimplantation genetic
      diagnosis (PGD). METHODS: Next generation sequencing (NGS) and Sanger sequencing
      analysis were carried out to define the inversion breakpoint. Multiple
      displacement amplification, amplification of breakpoint junction fragments,
      Sanger sequencing of exon 1 of ED1, haplotyping of informative short tandem
      repeat markers and gender determination were performed for PGD. RESULTS: NGS data
      of the proband sample revealed that the size of the possible inverted fragment
      was over 42Mb, spanning from position 26, 814, 206 to position 69, 231, 915 on
      the X chromosome. The breakpoints were confirmed by Sanger sequencing. A total of
      5 blastocyst embryos underwent trophectoderm biopsy. Two embryos were diagnosed
      as carriers and three were unaffected. Two unaffected blastocysts were
      transferred and a singleton pregnancy was achieved. Following confirmation by
      prenatal diagnosis, a healthy baby was delivered. CONCLUSIONS: This is the first
      report of an XLHED family with inv(X). ED1 is disrupted by the X chromosome
      inversion in this XLHED family and embryos with the X chromosomal abnormality can
      be accurately identified by means of PGD.

PMID- 29037842
TI  - Puerarin inhibits expression of tissue factor induced by oxidative low-density
      lipoprotein through activating the PI3K/Akt/eNOS pathway and inhibiting
      activation of ERK1/2 and NF-kappaB.
AB  - AIMS: The present study aimed to investigate whether puerarin regulated tissue
      factor (TF) expression induced by oxidative low-density lipoprotein (ox-LDL), an
      independent risk factor for atherosclerosis, and its mechanisms. MAIN METHODS: TF
      expression at the mRNA level was determined by reverse transcription-quantitative
      polymerase chain reaction, and its expression at the protein level, as well as
      other target proteins, was assessed by western blotting. Nitric oxide (NO)
      production was measured by a nitrate reduction method. KEY FINDINGS: Results
      demonstrated that treatment with ox-LDL (50mg/l) for 24h significantly increased
      (P<0.01) TF expression at the mRNA and protein levels in human umbilical vein
      endothelial cells (HUVECs). Such an ox-LDL exposure also triggered the
      dephosphorylation of Akt, resulting in a reduction of NO production and activated
      the extracellular signal-regulated kinase (ERK)1/2 and nuclear factor (NF)-kappaB
      signaling pathways. Pre-treatment with puerarin (50-200MUM) for 1h significantly
      attenuated the ox-LDL-induced TF expression, augmented the phosphorylation of
      Akt, with a resultant increase of the NO production, and inhibited the activation
      of ERK1/2 and NF-kappaB (P<0.01). However, this beneficial effect of puerarin
      (100MUM) was abolished by LY294002 (10MUM), an inhibitor of phosphoinositide 3
      kinase (PI3K), or NG-nitro-L-arginine methyl ester (100MUM), an inhibitor of NO
      synthase. SIGNIFICANCE: These results suggested that puerarin suppressed TF
      expression in HUVECs through activating the PI3K/Akt/endothelial nitric oxide
      synthase signaling pathway and inhibiting the activation of ERK1/2 and NF-kappaB.
      These findings suggested that puerarin possessed certain anticoagulation and may
      be a potential novel therapeutic drug for thrombosis in coronary artery disease.

PMID- 29037843
TI  - Spatio-Temporal Flow and Wall Shear Stress Mapping Based on Incoherent Ensemble
      Correlation of Ultrafast Contrast Enhanced Ultrasound Images.
AB  - In this study, a technique for high-frame-rate ultrasound imaging velocimetry
      (UIV) is extended first to provide more robust quantitative flow velocity mapping
      using ensemble correlation of images without coherent compounding, and second to
      generate spatio-temporal wall shear stress (WSS) distribution. A simulation
      model, which couples the ultrasound simulator with analytical flow solution, was
      implemented to evaluate its accuracy. It is shown that the proposed approach can
      reduce errors in velocity estimation by up to 10-fold in comparison with the
      coherent correlation approach. Mean errors (ME) of 3.2% and 8.6% were estimated
      under a steady flow condition, while 3.0% and 10.6% were found under a pulsatile
      condition for the velocity and wall shear rate (WSR) measurement, respectively.
      Appropriate filter parameters were selected to constrain the velocity profiles
      before WSR estimations and the effects of incorrect wall tracking were quantified
      under a controlled environment. Although accurate wall tracking is found to be
      critical in WSR measurement (as a 200 um deviation from the wall may yield up to
      a 60% error), this can be mitigated by HFR imaging (of up to 10 kHz) with
      contrast agents, which allow for improved differentiation of the wall-fluid
      boundaries. In vitro investigations on two carotid bifurcation phantoms, normal
      and diseased, were conducted, and their relative differences in terms of the flow
      patterns and WSR distribution were demonstrated. It is shown that high-frame-rate
      UIV technique can be a non-invasive tool to measure quantitatively the spatio
      temporal velocity and WSS distribution.

PMID- 29037844
TI  - Clinical Application of Contrast-Enhanced Ultrasound Using High-Frequency Linear
      Probe in the Detection of Small Colorectal Liver Metastases.
AB  - To compare the performance of contrast-enhanced ultrasound (CEUS) using high
      frequency linear and convex probes in the detection of small colorectal liver
      metastases (CRLMs). A total of 85 patients with 143 small CRLMs were evaluated.
      High-frequency ultrasound (US) and CEUS detected significantly more superficial
      lesions within 60 mm below the skin than a convex probe (p <0.05). The detection
      rate decreased in the chemotherapy group, especially when using a convex probe
      for US (p <0.05). By combining convex and linear probes, detection rates of US
      and CEUS were significantly higher than that of a convex or a linear probe alone
      (p <0.05). High-frequency US and CEUS helped to improve detection of small CRLMs
      and reduce the influence of chemotherapy. For patients with a high risk of CRLMs
      and those after chemotherapy, we recommend first scanning the liver by using a
      convex probe and subsequently screening the surface area of the liver and
      suspicious small lesions by using a linear probe.

PMID- 29037846
TI  - Altered bone density and stress distribution patterns in long-standing cubitus
      varus deformity and their effect during early osteoarthritis of the elbow.
AB  - OBJECTIVE: To quantify the bone density and stress distribution patterns in long
      standing cubitus varus and clarify the effects of the deformity on bone density.
      DESIGN: We created three-dimensional computed tomography (CT) elbow models from
      21 patients with long-standing cubitus varus deformities without advanced
      osteoarthritis (OA) and assessed the deformity by superimposing the affected
      humerus onto a mirror-image of the contralateral normal. Elbows were divided into
      13 regions before measuring the bone density of each region and comparing the
      percentage of high-density volume (%HDV) between affected and normal sides. We
      constructed finite element models and quantitatively analyzed stress
      distribution. RESULTS: Average degrees of deformities were 20.1 degrees  of
      varus, 6.4 degrees  of extension, and 12.7 degrees  of internal rotation. The
      medial side of the affected humerus and ulna, Anteromedial trochlea (P < 0.001),
      Medial coronoid (P = 0.004), and Medial olecranon (P = 0.049) had significantly
      higher %HDVs than their normal counterparts. Conversely, %HDVs on the affected
      lateral side, Capitellum (P < 0.001), Anterolateral trochlea (P = 0.010),
      Posterolateral trochlea (P < 0.001), Lateral coronoid (P = 0.007), and Lateral
      olecranon (P < 0.001) were significantly lower than the normal side. The affected
      radial head %HDVs at Anterolateral and Posteromedial quadrants were high (P =
      0.007) and low (P = 0.007), respectively. The bone density distribution coincided
      with stress distribution patterns revealed by finite element analysis (FEA),
      except in the lateral region influenced by forearm rotation. CONCLUSIONS:
      Repetitive stress on the medial elbow may alter bone density distribution
      patterns, probably presenting from early stage of OA.

PMID- 29037845
TI  - Implementing core NICE guidelines for osteoarthritis in primary care with a model
      consultation (MOSAICS): a cluster randomised controlled trial.
AB  - OBJECTIVE: To determine the effectiveness of a model osteoarthritis consultation,
      compared with usual care, on physical function and uptake of National Institute
      for Health and Care Excellence (NICE) osteoarthritis recommendations, in adults
      >=45 years consulting with peripheral joint pain in UK general practice. METHOD:
      Two-arm cluster-randomised controlled trial with baseline health survey. Eight
      general practices in England. PARTICIPANTS: 525 adults >=45 years consulting for
      peripheral joint pain, amongst 28,443 population survey recipients. Four
      intervention practices delivered the model osteoarthritis consultation to
      patients consulting with peripheral joint pain; four control practices continued
      usual care. The primary clinical outcome of the trial was the SF-12 physical
      component score (PCS) at 6 months; the main secondary outcome was uptake of NICE
      core recommendations by 6 months, measured by osteoarthritis quality indicators.
      A Linear Mixed Model was used to analyse clinical outcome data (SF-12 PCS).
      Differences in quality indicator outcomes were assessed using logistic
      regression. RESULTS: 525 eligible participants were enrolled (mean age 67.3
      years, SD 10.5; 59.6% female): 288 from intervention and 237 from control
      practices. There were no statistically significant differences in SF-12 PCS: mean
      difference at the 6-month primary endpoint was -0.37 (95% CI -2.32, 1.57). Uptake
      of core NICE recommendations by 6 months was statistically significantly higher
      in the intervention arm compared with control: e.g., increased written exercise
      information, 20.5% (7.9, 28.3). CONCLUSION: Whilst uptake of core NICE
      recommendations was increased, there was no evidence of benefit of this
      intervention, as delivered in this pragmatic randomised trial, on the primary
      outcome of physical functioning at 6 months. TRIAL REGISTRATION: ISRCTN06984617.

PMID- 29037847
TI  - The added mass forces in insect flapping wings.
AB  - The added mass forces of three-dimensional (3D) flapping wings of some
      representative insects, and the accuracy of the often used simple two-dimensional
      (2D) method, are studied. The added mass force of a flapping wing is calculated
      by both 3D and 2D methods, and the total aerodynamic force of the wing is
      calculated by the CFD method. Our findings are as following. The added mass force
      has a significant contribution to the total aerodynamic force of the flapping
      wings during and near the stroke reversals, and the shorter the stroke amplitude
      is, the larger the added mass force becomes. Thus the added mass force could not
      be neglected when using the simple models to estimate the aerodynamics force,
      especially for insects with relatively small stroke amplitudes. The accuracy of
      the often used simple 2D method is reasonably good: when the aspect ratio of the
      wing is greater than about 3.3, error in the added mass force calculation due to
      the 2D assumption is less than 9%; even when the aspect ratio is 2.8
      (approximately the smallest for an insect), the error is no more than 13%.

PMID- 29037848
TI  - Molecular mechanism of mercury-induced reproductive impairments in banded
      gourami, Trichogaster fasciata.
AB  - Mercury is one of the key pollutants responsible for the degradation of natural
      aquatic ecosystems. Among the different forms of mercury that exist in the
      environment, mercuric chloride (HgCl2) is the dominant pollutant for freshwater
      environments as it is used as an ingredient in antiseptics, disinfectants and
      preservatives, insecticides, batteries and in metallurgical and photographic
      operations. Pollutant may exert their action on organisms or populations by
      affecting their normal endocrine function as well as reproduction. Thus, the
      present study tried to understand the effect of mercuric chloride (HgCl2) on
      reproductive function and to decipher the molecular mechanism of Hg-induced
      reproductive impairments of female Trichogaster fasciata. Both in vivo and in
      vitro experiments were performed by using ecologically relevant doses of HgCl2
      and the resulting effects on follicular development, steroidogenic potentiality,
      aromatase activity, aromatase gene expression and steroidogenic factor-1 (SF-1)
      expression pattern were analysed. In vivo exposure to HgCl2 caused reproductive
      impairments as shown by the inhibitory role of HgCl2 on follicular development,
      steroid biosynthesis and SF-1 activity. In vitro experiments revealed that
      aromatase activity, steroidogenesis, aromatase and SF-1 expression were blocked
      by HgCl2. The results obtained from this study contribute to understand the
      molecular mechanism of HgCl2-induced reproductive impairment of T. fasciata.

PMID- 29037850
TI  - Comparison of DNA fragmentation of frozen-thawed epididymal sperm of dogs using
      Sperm Chromatin Structure Analysis and Sperm Chromatin Dispersion test.
AB  - The aim of this study was to compare sperm DNA fragmentation of frozen-thawed
      epididymal sperm of dogs using the SCSA (Sperm Chromatin Structure Assay) and
      SCDt (Sperm Chromatin Dispersion test). For this purpose, epididymis from
      neutered dogs were minced and incubated in a Tris-based extender. The recovered
      sperm were frozen in a two-step cooling protocol with Tris-based, egg yolk
      extender and increasing glycerol concentrations, and stored in liquid nitrogen.
      After thawing, each replica was incubated at 38 degrees C for 24h. Sperm DNA
      fragmentation index (sDFi) was assessed by SCSA and SCDt at 0, 3, 6 and 24h of
      incubation and compared within treatments. The relationship and agreement between
      techniques were evaluated by Pearson's coefficient and Intraclass Correlation
      Coefficient (ICC). The results were expressed as mean+/-standard error of the
      mean (SEM). Both techniques indicated there was a significant increase of DNA
      fragmentation after 24h of incubation. Moderate correlation (r=0.65; P<0.01) but
      lack of agreement (ICC=0.451; P>0.05) was found between SCSA and SCDt. The lack
      of agreement indicates that SCSA and SCDt measure different aspects of DNA
      fragmentation. Four halo morphologies were detected after 24h of incubation using
      the SCDt: un-fragmented DNA with a small halo, fragmented DNA with large halo and
      two new halo presentations never described before for dog sperm: receding sperm
      with a disappearing halo and "bald" sperm without chromatin dispersion halo
      around the core. Sperm without a halo of chromatin dispersion are not described
      by the manufacturer and are similar to un-fragmented sperm, which could lead to
      erroneous results when using the SCDt. Further studies with different incubation
      periods and including the new morphologies described in this study should be
      performed. In conclusion, although SCSA and SCDt can evaluate the changes in the
      sperm DNA fragmentation dynamics of frozen-thawed epididymal dog sperm, these
      provided different findings on sperm DNA fragmentation.

PMID- 29037849
TI  - Letrozole induced low estrogen levels affected the expressions of duodenal and
      renal calcium-processing gene in laying hens.
AB  - Estrogen regulates the calcium homeostasis in hens, but the mechanisms involved
      are still unclear fully. In this study, we investigated whether letrozole (LZ)
      induced low estrogen levels affected the calcium absorption and transport in
      layers. In the duodenum, we observed a significant decrease of mRNA expressions
      of Calbindin-28k (CaBP-28k) and plasma membrane Ca2+-ATPase (PMCA 1b) while CaBP
      28k protein expression was declined in birds with LZ treatment, and the mRNA
      levels of duodenal transient receptor potential vanilloid 6 (TRPV6) and Na+/Ca2+
      exchanger 1 (NCX1) were not affected. Interestingly, we observed the different
      changes in the kidney. The renal mRNA expressions of TRPV6 and NCX1 were
      unregulated while the PMCA1b was down-regulated in low estrogen layers, however,
      the CaBP-28k gene and protein expressions were no changed in the kidney.
      Furthermore, it showed that the duodenal estradiol receptor 2 (ESR2) transcripts
      rather than parathyroid hormone 1 receptor (PTH1R) and calcitonin receptor
      (CALCR) played key roles to down-regulate calcium transport in LZ-treated birds.
      In conclusion, CaBP-28k, PMCA 1b and ESR2 genes in the duodenum may be primary
      targets for estrogen regulation in order to control calcium homeostasis in hens.

PMID- 29037853
TI  - This Month in AJP.
AB  - The following highlights summarize research articles that are published in the
      current issue of The American Journal of Pathology.

PMID- 29037851
TI  - Cobalamin-Associated Superoxide Scavenging in Neuronal Cells Is a Potential
      Mechanism for Vitamin B12-Deprivation Optic Neuropathy.
AB  - Chronic deficiency of vitamin B12 is the only nutritional deficiency definitively
      proved to cause optic neuropathy and loss of vision. The mechanism by which this
      occurs is unknown. Optic neuropathies are associated with death of retinal
      ganglion cells (RGCs), neurons that project their axons along the optic nerve to
      the brain. Injury to RGC axons causes a burst of intracellular superoxide, which
      then signals RGC apoptosis. Vitamin B12 (cobalamin) was recently shown to be a
      superoxide scavenger, with a rate constant similar to superoxide dismutase. Given
      that vitamin B12 deficiency causes an optic neuropathy through unknown mechanisms
      and that it is a potent superoxide scavenger, we tested whether cobalamin, a
      vitamin B12 vitamer, would be neuroprotective in vitro and in vivo. We found that
      cobalamin scavenged superoxide in neuronal cells in vitro treated with the
      reduction-oxidation cycling agent menadione. In vivo confocal scanning laser
      ophthalmoscopy demonstrated that optic nerve transection in Long-Evans rats
      increased superoxide levels in RGCs. The RGC superoxide burst was significantly
      reduced by intravitreal cobalamin and resulted in increased RGC survival. These
      data demonstrate that cobalamin may function as an endogenous neuroprotectant for
      RGCs through a superoxide-associated mechanism.

PMID- 29037852
TI  - The Hajdu Cheney Mutation Is a Determinant of B-Cell Allocation of the Splenic
      Marginal Zone.
AB  - The neurogenic locus notch homolog protein (Notch)-2 receptor is a determinant of
      B-cell allocation, and gain-of-NOTCH2-function mutations are associated with
      Hajdu-Cheney syndrome (HCS), a disease presenting with osteoporosis and acro
      osteolysis. We generated a mouse model reproducing the HCS mutation (Notch2HCS),
      and heterozygous global mutant mice displayed gain-of-Notch2 function. In the
      mutant spleen, the characteristic perifollicular rim marking the marginal zone
      (MZ), which is the interface between the nonlymphoid red pulp and the lymphoid
      white pulp, merged with components of the white pulp. As a consequence, the MZ of
      Notch2HCS mice occupied most of the splenic structure. To explore the mechanisms
      involved, lymphocyte populations from the bone marrow and spleen were harvested
      from heterozygous Notch2HCS mice and sex-matched control littermates and analyzed
      by flow cytometry. Notch2HCS mice had an increase in CD21/35highCD23- splenic MZ
      B cells of approximately fivefold and a proportional decrease in splenic
      follicular B cells (CD21/35intCD23+) at 1, 2, and 12 months of age. Western blot
      analysis revealed that Notch2HCS mutant splenocytes had increased phospho-Akt and
      phospho-Jun N-terminal kinase, and gene expression analysis of splenic CD19+ B
      cells demonstrated induction of Hes1 and Hes5 in Notch2HCS mutants. Anti-Notch2
      antibodies decreased MZ B cells in control and Notch2HCS mice. In conclusion,
      Notch2HCS mutant mice have increased mature B cells in the MZ of the spleen.

PMID- 29037854
TI  - Overexpression of Flap Endonuclease 1 Correlates with Enhanced Proliferation and
      Poor Prognosis of Non-Small-Cell Lung Cancer.
AB  - Flap endonuclease 1 (FEN1) plays a crucial role in both DNA replication and
      damage repair. In this study, FEN1 expression and its clinical-pathologic
      significance in non-small-cell lung cancer (NSCLC) was investigated. Quantitative
      RT-PCR and immunohistochemistry analysis identified that both FEN1 mRNA and
      protein were highly overexpressed in about 36% of 136 cancer tissues compared to
      adjacent tissues, in which FEN1 was generally undetectable. Notably, patients
      with FEN1-overexpressed cancers were prone to have poor differentiation and poor
      prognosis. A strong positive correlation between the levels of FEN1 and Ki-67
      staining was identified in these NSCLC tissues (r = 0.485), suggesting
      overexpressed FEN1 conferred a proliferative advantage to NSCLC. Furthermore,
      knockdown of FEN1 resulted in G1/S or G2/M phase cell cycle arrest and suppressed
      in vitro cellular proliferation in NSCLC cancer cells. Consistently, a selective
      FEN1 inhibitor was shown to effectively inhibit cellular proliferation of NSCLC
      cells in a dose-dependent manner. Additionally, knockdown of FEN1 significantly
      attenuated homologous DNA repair efficiency and enhanced cytotoxic effects of
      cisplatin in NSCLC cells. Taken together, these findings have indicated that
      overexpressed FEN1 represents a prognostic biomarker and potential therapeutic
      target for NSCLC treatment, which warrants further study.

PMID- 29037855
TI  - Nephrosphere-Derived Cells Are Induced to Multilineage Differentiation when
      Cultured on Human Decellularized Kidney Scaffolds.
AB  - In end-stage chronic kidney disease, the option of organ transplantation is
      limited because of the scarce availability of kidneys. The combination of stem
      cell research, regenerative medicine, and tissue engineering seems a promising
      approach to produce new transplantable kidneys. Currently, the possibility to
      repopulate naturally obtained scaffolds with cells of different sources is
      advancing. Our aim was to test, for the first time, whether the nephrosphere (NS)
      cells, composed by renal stem/progenitor-like cells, were able to repopulate
      different nephron portions of renal extracellular matrix scaffolds obtained after
      decellularization of human renal tissue slices. Our decellularization protocol
      enabled us to obtain a completely acellular renal scaffold while maintaining the
      extracellular matrix structure and composition in terms of collagen IV, laminin,
      and fibronectin. NS cells, cultured on decellularized renal scaffolds with basal
      medium, differentiated into proximal and distal tubules as well as endothelium,
      as highlighted by histology and by the specific expression of epithelial
      cytokeratin 8.18, proximal tubular CD10, distal tubular cytokeratin 7, and
      endothelial von Willebrand factor markers. Endothelial medium promoted the
      differentiation toward the endothelium, whereas epithelial medium promoted the
      differentiation toward the epithelium. NS cells seem to be a good tool for
      scaffold repopulation, paving the way for experimental investigations focused on
      whole-kidney reconstruction.

PMID- 29037857
TI  - Exploring the Role of IL-32 in HIV-Related Kaposi Sarcoma.
AB  - The intracellular proinflammatory mediator IL-32 is associated with tumor
      progression; however, the mechanisms remain unknown. We studied IL-32 mRNA
      expression as well as expression of other proinflammatory cytokines and
      mediators, including IL-1alpha, IL-1beta, IL-6, IL-8, tumor necrosis factor (TNF)
      alpha, the proangiogenic and antiapoptotic enzyme cyclooxygenase-2, the IL-8
      receptor C-X-C chemokine receptor (CXCR) 1, and the intracellular kinase focal
      adhesion kinase-1. The interaction of IL-32 expression with expression of IL-6,
      TNF-alpha, IL-8, and cyclooxygenase-2 was also investigated. Biopsy specimens of
      11 HIV-related, 7 non-HIV-related Kaposi sarcoma (KS), and 7 normal skin tissues
      (NSTs) of Dutch origin were analyzed. RNA was isolated from the paraffin
      material, and gene expression levels of IL-32 alpha, beta, and gamma isoforms,
      IL1a, IL1b, IL6, IL8, TNFA, PTGS2, CXCR1, and PTK2 were determined using real
      time quantitative PCR. Significantly higher expression of IL-32beta and IL
      32gamma isoforms was observed in HIV-related KS biopsy specimens compared with
      non-HIV-related KS and NST. The splicing ratio of the IL-32 isoforms showed IL
      32gamma as the highest expressed isoform, followed by IL-32beta, in HIV-related
      KS cases compared with non-HIV-related KS and NST. Our data suggest a possible
      survival mechanism by the splicing of IL-32gamma to IL-32beta and also IL-6, IL
      8, and CXCR1 signaling pathways to reverse the proapoptotic effect of the IL
      32gamma isoform, leading to tumor cell survival and thus favoring tumor
      progression.

PMID- 29037856
TI  - Platelet CD40 Mediates Leukocyte Recruitment and Neointima Formation after
      Arterial Denudation Injury in Atherosclerosis-Prone Mice.
AB  - The role of platelets in the development of thrombosis and abrupt closure after
      angioplasty is well recognized. However, the direct impact of platelets on
      neointima formation after arterial injury remains undetermined. Herein, we show
      that neointima formation after carotid artery wire injury reduces markedly in
      CD40-/- apolipoprotein E-deficient (apoE-/-) mice but only slightly in CD40
      ligand-/-apoE-/- mice, compared with apoE-/- mice. Wild-type and CD40-deficient
      platelets were isolated from blood of apoE-/- and CD40-/-apoE-/- mice,
      respectively. The i.v. injection of thrombin-activated platelets into CD40-/-apoE
      /- mice was performed every 5 days, starting at 2 days before wire injury.
      Injection of wild-type platelets promoted neointima formation, which was
      associated with increased inflammation by stimulating leukocyte recruitment via
      up-regulation of circulating platelet surface P-selectin expression and the
      formation of platelet-leukocyte aggregates. It was also associated with further
      promoting the luminal deposition of platelet-derived regulated on activation
      normal T cell expressed and secreted/chemokine (C-C motif) ligand 5 and
      expression of monocyte chemoattractant protein-1 and vascular cell adhesion
      molecule 1 in wire-injured carotid arteries. Remarkably, all these inflammatory
      actions by activated platelets were abrogated by lack of CD40 on injected
      platelets. Moreover, injection of wild-type platelets inhibited endothelial
      recovery in wire-injured carotid arteries, but this effect was also abrogated by
      lack of CD40 on injected platelets. Results suggest that platelet CD40 plays a
      pivotal role in neointima formation after arterial injury and might represent an
      attractive target to prevent restenosis after vascular interventions.

PMID- 29037858
TI  - Co-Localization of Insulin-Like Growth Factor Binding Protein-1, Casein Kinase
      2beta, and Mechanistic Target of Rapamycin in Human Hepatocellular Carcinoma
      Cells as Demonstrated by Dual Immunofluorescence and in Situ Proximity Ligation
      Assay.
AB  - Insulin-like growth factor binding protein (IGFBP)-1 influences fetal growth by
      modifying insulin-like growth factor-I (IGF-I) bioavailability. IGFBP-1
      phosphorylation, which markedly increases its affinity for IGF-I, is regulated by
      mechanistic target of rapamycin (mTOR) and casein kinase (CSNK)-2. However, the
      underlying molecular mechanisms remain unknown. We examined the cellular
      localization and potential interactions of IGFBP-1, CSNK-2beta, and mTOR as a
      prerequisite for protein-protein interaction. Analysis of dual immunofluorescence
      images indicated a potential perinuclear co-localization between IGFBP-1 and CSNK
      2beta and a nuclear co-localization between CSNK-2beta and mTOR. Proximity
      ligation assay (PLA) indicated proximity between IGFBP-1 and CSNK-2beta as well
      as mTOR and CSNK-2beta but not between mTOR and IGFBP-1. Three-dimensional
      rendering of the PLA images validated that IGFBP-1 and CSNK-2beta interactions
      were in the perinuclear region and mTOR and CSNK-2beta interactions were also
      predominantly perinuclear rather than nuclear as indicated by mTOR and CSNK-2beta
      co-localization. Compared with control, hypoxia and rapamycin treatment showed
      markedly amplified PLA signals for IGFBP-1 and CSNK-2beta (approximately 18-fold,
      P = 0.0002). Stable isotope labeling with multiple reaction monitoring-mass
      spectrometry demonstrated that hypoxia and rapamycin treatment increased IGFBP-1
      phosphorylation at Ser98/Ser101/Ser119/Ser174 but most considerably (106-fold) at
      Ser169. We report interactions between CSNK-2beta and IGFBP-1 as well as mTOR and
      CSNK-2beta, providing strong evidence of a mechanistic link between mTOR and IGF
      I signaling, two critical regulators of cell growth via CSNK-2.

PMID- 29037859
TI  - Chorionic Gonadotropin-beta Modulates Epithelial-Mesenchymal Transition in
      Colorectal Carcinoma Metastasis.
AB  - Ectopic production of free beta human chorionic gonadotropin (hCGbeta) has been
      associated with aggressive behavior in non-trophoblastic tumors. hCGbeta shares
      common evolutionary sequences with transforming growth factor-beta (TGF-beta),
      which represents a major driving force of epithelial-to-mesenchymal transition
      (EMT). In this study, we examined the biological roles of hCGbeta during EMT and
      its clinical significance in colorectal cancer (CRC) progression. Eighty CRC
      specimens and 54 preoperative serum samples were analyzed. hCGbeta-overexpressing
      human CRC cell lines were examined for invasiveness and tumorigenicity, and the
      expression of EMT-associated genes was investigated. In human CRC, histologic
      hCGbeta positivity [13/80 (16.3%)] was lower than serologic hCGbeta positivity
      [13/54 (24.1%)]. However, it was significantly correlated with several
      clinicopathological features and unfavorable outcome (P < 0.05). hCGbeta
      overexpressing cell lines had increased invasiveness, migratory ability, and
      metastatic potential in mice (P < 0.01). Western blot, PCR, and microarray
      analyses showed hCGbeta altered expression of EMT-related genes, including E
      cadherin, phosphorylated SMAD2, SNAIL, and TWIST. hCGbeta-induced SNAIL and TWIST
      overexpression levels were reversible by type I and type II TGF-beta receptor
      inhibitors (P < 0.05). hCGbeta thus induces EMT via the TGF-beta signaling
      pathway, and it may represent a molecular target in CRC treatment.

PMID- 29037860
TI  - Neurotrophin Receptors TrkA, p75NTR, and Sortilin Are Increased and Targetable in
      Thyroid Cancer.
AB  - Neurotrophin receptors are emerging targets in oncology, but their
      clinicopathologic significance in thyroid cancer is unclear. In this study, the
      neurotrophin tyrosine receptor kinase TrkA (also called NTRK1), the common
      neurotrophin receptor p75NTR, and the proneurotrophin receptor sortilin were
      analyzed with immunohistochemistry in a cohort of thyroid cancers (n = 128) and
      compared with adenomas and normal thyroid tissues (n = 62). TrkA was detected in
      20% of thyroid cancers, compared with none of the benign samples (P = 0.0007).
      TrkA expression was independent of histologic subtypes but associated with lymph
      node metastasis (P = 0.0148), suggesting the involvement of TrkA in tumor
      invasiveness. Nerves in the tumor microenvironment were positive for TrkA. p75NTR
      was overexpressed in anaplastic thyroid cancers compared with papillary and
      follicular subtypes (P < 0.0001). Sortilin was overexpressed in thyroid cancers
      compared with benign thyroid tissues (P < 0.0001). Neurotrophin receptor
      expression was confirmed in a panel of thyroid cancer cell lines at the mRNA and
      protein levels. Functional investigations using the anaplastic thyroid cancer
      cell line CAL-62 found that siRNA against TrkA, p75NTR, and sortilin decreased
      cell survival and cell migration through decreased SRC and ERK activation.
      Together, these data reveal TrkA, p75NTR, and sortilin as potential therapeutic
      targets in thyroid cancer.

PMID- 29037862
TI  - Artificial Urinary Sphincter in Male Patients with Spina Bifida: Comparison of
      Perioperative and Functional Outcomes between Bulbar Urethra and Bladder Neck
      Cuff Placement.
AB  - PURPOSE: We evaluated the perioperative and long-term functional outcomes of
      bladder neck and peribulbar cuff placement of an artificial urinary sphincter in
      a population of adult male patients with spinal dysraphism. MATERIALS AND
      METHODS: We retrospectively analyzed the French spina bifida network database.
      Patients who underwent implantation of an artificial urinary sphincter from
      January 1985 to November 2015 were selected and stratified into 2 groups
      according to cuff location, that is bladder neck vs bulbar urethra. Explantation
      free and revision-free device survival was estimated by the Kaplan-Meier method
      and compared with the log rank test. Cox regression models were created to assess
      prognostic factors of artificial urinary sphincter device failure. RESULTS: A
      total of 65 patients were included in study. Most patients were not wheelchair
      bound. The cuff was implanted around the bulbar urethra at 46 procedures (59%)
      and around the bladder neck in 32 (41%). In the peribulbar and bladder neck
      groups median revision-free device survival was 11.7 and 14.3 years, respectively
      (p = 0.73). Median explantation-free device survival was 18.5 and 24.5 years,
      respectively (p = 0.08). On multivariate analysis clean intermittent
      catheterization was the only predictor of artificial urinary sphincter device
      failure. Cuff location had no influence. At the last followup satisfactory
      continence was similar in the 2 groups (83% vs 75%, p = 0.75). CONCLUSIONS: In
      male patients with spinal dysraphism morbidity and functional outcomes were
      similar for bladder neck and bulbar urethra cuff placement but with a trend
      toward longer survival without explantation in the bladder neck group. Clean
      intermittent catheterization was the only predictor of shorter device survival on
      multivariate analysis.

PMID- 29037861
TI  - Biological Behavior and Long-Term Outcomes of Carcinoma In Situ in Upper Urinary
      Tract Managed by Radical Nephroureterectomy.
AB  - PURPOSE: In patients with urothelial carcinoma CIS (carcinoma in situ) generally
      has a poor prognosis. However, to our knowledge the outcomes of pure/primary CIS
      and the behavior of CIS concomitant with pTa-pT4 upper tract urothelial carcinoma
      managed by nephroureterectomy have not been previously specified. We explored the
      biological and prognostic features of concomitant CIS compared with those of
      pure/primary CIS. MATERIALS AND METHODS: We queried a multicenter upper tract
      urothelial carcinoma database. Data from NUOG (Nishinihon Uro-Oncology Group)
      were analyzed, including patient gender, age, presence of bladder cancer and pT
      stage. Clinicopathological features were compared between the different subtypes.
      Cancer specific and overall survival, and the relative excess risk of death were
      estimated by CIS subtype. RESULTS: We identified 163 patients with CIS in the
      upper urinary tract, of whom pure/primary CIS was noted in 24.5%. In the
      concomitant CIS cohort the pathological diagnosis of the nonCIS region was pTa,
      pT1, pT2, pT3 and pT4 in 4.9%, 22.8%, 25.2%, 44.7% and 1.6% of patients,
      respectively. The sensitivity of a selective urine cytology test was higher in
      the pure/primary CIS group than in the concomitant CIS group (60.0% vs 37.4%). At
      a median followup of 32 months 10-year estimated mean cancer specific survival
      was 92.4 months (range 83.7 to 101.0) in the overall CIS cohort. Ten-year
      estimated mean cancer specific survival in patients with pure/primary CIS was
      significantly longer than in patients with concomitant carcinoma in situ (111.8
      months, range 101.0 to 122.6 vs 85.89, range 75.3 to 96.5, log rank p = 0.007).
      CONCLUSIONS: Patients presenting with concomitant CIS have a worse outcome than
      those who present with pure/primary CIS, suggesting a need to differentiate these
      2 entities in the treatment decision process.

PMID- 29037863
TI  - Outer Membrane Protein OmpB Methylation May Mediate Bacterial Virulence.
AB  - Methylation of outer membrane proteins (OMPs) has been implicated in bacterial
      virulence. Lysine methylation in rickettsial OmpB is correlated with rickettsial
      virulence, and N- and O-methylations are also observed in virulence-relevant OMPs
      from several pathogenic bacteria that cause typhus, leptospirosis, tuberculosis,
      and anaplasmosis. We summarize recent findings on the structure of methylated
      OmpB, biochemical characterization, and crystal structures of OmpB
      methyltransferases. Native rickettsial OmpB purified from highly virulent strains
      contains multiple clusters of trimethyllysine, in contrast with mostly
      monomethyllysine, and no trimethyllysine is found in an avirulent strain. Crystal
      structure of the methyltransferases reveals mechanistic insights for catalysis,
      and a working model is discussed for this unusual post-translational
      modification.

PMID- 29037864
TI  - Can bladder fibrosis in congenital urinary tract obstruction be reversed?
AB  - A variety of conditions exists in adults and children in which functional or
      anatomical urinary tract obstructions cause bladder fibrosis, which reduces the
      bladder's ability to store and empty urine. Current surgical procedures include
      removal of the obstructions to facilitate bladder emptying or prompt prenatal or
      postnatal spinal closure to prevent further neurogenic damage. Bladder fibrosis
      may occur, and it can get worse if a flow hindrance persists or deteriorates.
      Anti-fibrotic therapeutic strategies that target a variety of factors have been
      developed in animal models, but currently there are no anti-fibrotic therapies
      available for clinical use. This review examines the pathogenesis of bladder
      fibrosis that is caused by congenital obstructions of the lower urinary tract,
      and it focuses on the principal signalling factors and potential treatment
      modalities.

PMID- 29037865
TI  - Voiding school as a treatment of daytime incontinence or enuresis: Children's
      experiences of the intervention.
AB  - BACKGROUND: Daytime incontinence and enuresis are common problems in otherwise
      healthy children, and negatively influence their social lives and self-esteem.
      Motivation for treatment is often a real clinical problem. Children's experiences
      of their incontinence treatments have not been previously described. OBJECTIVE:
      The aim of this study was to describe children's experiences of the Voiding
      School intervention as a treatment for their incontinence. STUDY DESIGN: A
      qualitative, descriptive focus-group study with a purposive sample was conducted
      at a Finish university hospital in 2014. Children aged 6-12 years participated in
      the Voiding School at an outpatient clinic. The intervention included two 1-day
      group visits 2 months apart. The educational content was based on the
      International Children Continence Society's standards for urotherapy. The
      education was delivered with child-oriented teaching methods. At the end of the
      second visit, 19 children were interviewed in five groups. Data were analysed
      with inductive content analysis. RESULTS: The children described incontinence as
      an embarrassing problem, which they had to hide at any cost. They had experienced
      bullying and social isolation because of it. Normal outpatient visits emphasized
      adult-to-adult communication, which made the children feel like outsiders. The
      children perceived the Voiding School as a nice and child-oriented experience.
      Making new friends was especially important to younger boys who felt that the
      Voiding School day was too long and issue-oriented. In the Voiding School, videos
      and 'learning by doing' helped the children to understand the basis of given
      advice, and they were able to learn new habits, which gave them control over the
      incontinence; this helped them to become 'the boss of the bladder'. Sharing
      experiences and improvements in their incontinence with their peers supported the
      children's self-esteem and encouraged them to do new things, such as staying
      overnight with friends. These experiences helped them to acquire control over the
      problem (Summary Figure). DISCUSSION: According to the children's experiences,
      normal outpatient visits were only appointments for adults, and not very useful
      for children. In the Voiding School, they were respected as being the main
      person, and their views were listened to. The results underlined the importance
      of a child-oriented approach to patient education with regard to children, and
      provided encouragement to further develop the intervention. CONCLUSION: Child
      orientation, peer support, learning by doing, and understanding the cause and
      effect helped children to gain control over their bladders. Based on the
      children's experiences, this could be achieved by a voiding school.

PMID- 29037866
TI  - Increasing genetic diversity of H5N6 avian influenza virus in China: A serious
      threat to persistence and dissemination in Guangdong province.

PMID- 29037867
TI  - Costunolide specifically binds and inhibits thioredoxin reductase 1 to induce
      apoptosis in colon cancer.
AB  - Colon cancer is one of the leading causes of cancer-related deaths. A natural
      sesquiterpene lactone, costunolide (CTD), showed inhibition of cancer
      development. However, the underlying mechanisms are not known. Here, we have
      examined the therapeutic activity and novel mechanisms of the anti-cancer
      activities of CTD in colon cancer cells. Using SPR analysis and enzyme activity
      assay on recombinant TrxR1 protein, our results show that CTD directly binds and
      inhibits the activity of TrxR1, which caused enhanced generation of ROS and led
      to ROS-dependent endoplasmic reticulum stress and cell apoptosis in colon cancer
      cells. Overexpression of TrxR1 in HCT116 cells reversed CTD-induced cell
      apoptosis and ROS increase. CTD treatment of mice implanted with colon cancer
      cells showed tumor growth inhibition and reduced TrxR1 activity and ROS level. In
      addition, it was observed that TrxR1 was significantly up-regulated in existing
      colon cancer gene database and clinically obtained colon cancer tissues. Our
      studies have uncovered the mechanism underlying the biological activity of CTD in
      colon cancer and suggest that targeting TrxR1 may prove to be beneficial as a
      treatment option.

PMID- 29037869
TI  - Uremic leontiasis ossea, a rare presentation of severe renal osteodystrophy
      secondary to hyperparathyroidism.
AB  - Renal osteodystrophy is a common complication of end-stage renal failure
      patients. It's most severe osseous complication is characterized by massive
      thickening of the cranial vault and facial bones, called uremic leontiasis ossea
      (ULO), with only few cases reported in the literature. A case of a 47-year-old
      female patient with ULO is presented. Physical examination showed enlargement of
      the jaws, which hinders proper ventilation and feeding. The computed tomography
      examination showed marked osseous proliferation in the jaws causing severe bony
      expansion and loss of normal bony architecture in the skull and the skull base.
      The most relevant clinical, histopathological and laboratory findings are
      discussed. The uremic leontiasis ossea causes significant aesthetic and
      functional changes. Correct diagnosis and management of the factors responsible
      for the development of bone lesions due to altered bone metabolism are key
      factors. The maxillofacial surgeon must have the proper knowledge of patient's
      medical condition and bone maturation status to address an adequate surgical
      strategy.

PMID- 29037868
TI  - The fungal neurotoxin penitrem A induces the production of reactive oxygen
      species in human neutrophils at submicromolar concentrations.
AB  - Penitrem A is a fungal neurotoxin that recurrently causes intoxication in
      animals, and occasionally also in humans. We have previously reported that
      penitrem A induced the production of reactive oxygen species (ROS) in rat
      cerebellar granule cells, opening for a new mechanism of action for the
      neurotoxin. The aim of this study was to examine the potential of penitrem A to
      induce ROS production in isolated human neutrophil granulocytes, and to study
      possible mechanisms involved. Penitrem A significantly increased the production
      of ROS in human neutrophils at concentrations as low as 0.25MUM (40% increase
      over basal levels), as measured with the DCF fluorescence assay. The EC50
      determined for the production of ROS by penitrem A was 3.8MUM. The maximal
      increase in ROS production was approximately 330% over basal levels at a
      concentration of 12.5MUM. ROS formation was significantly inhibited by the
      antioxidant vitamin E (50MUM), the intracellular Ca+2 chelator BAPTA-AM (5MUM),
      the mitogen activated protein kinase kinase (MEK) 1/2 and 5 inhibitor U0126 (1
      and 10MUM), the p38 mitogen activated protein kinase (MAPK) inhibitor SB203580
      (1MUM), the c-Jun amino-terminal kinase (JNK) inhibitor SP600125 (10MUM), and the
      calcineurin inhibitors FK-506 and cyclosporine A (1.5 and 0.5MUM, respectively).
      These finding suggest that penitrem A is able to induce an increase in ROS
      production in neutrophils via the activation of several MAPK-signalling pathways.
      We suggest that this increase may partly explain the pathophysiology generated by
      penitrem A neuromycotoxicosis in both humans and animals.

PMID- 29037870
TI  - The antibacterial and anti-inflammatory investigation of Lawsonia Inermis-gelatin
      starch nano-fibrous dressing in burn wound.
AB  - The aim of this study was to develop a new bioactive gelatin-oxidized starch
      nanofibers containing Lawsonia Inermis (henna) for treating second-degree burn
      wounds. Continuous, smooth, and bead-free fibers were obtained when the gelatin
      starch ratio was 70/30.Additionally, the fiber dimeter was reduced with
      increasing henna content. The successful loading of henna in the gelatin-oxidized
      starch nanofibers was approved using Fourier transform infrared spectroscopy and
      Differential scanning calorimetry. Moreover, the addition of henna to the gelatin
      oxidized starch nanomatrix enhanced fibroblasts attachment, proliferation,
      collagen secretion, and antibacterial activity. In vivo studies showed that the
      nanofibers loaded with henna accelerated wound closure remarkably with the
      absence of detrimental suppurative reaction at the site of the burn wound. The
      CD68 immunohistochemical stained wound images showed that treating the burn wound
      sites with gelatin-oxidized starch-henna reduced the inflammatory response and
      macrophage numbers significantly.

PMID- 29037871
TI  - Moringa oleifera seed lectin inhibits Ehrlich ascites carcinoma cell growth by
      inducing apoptosis through the regulation of Bak and NF-kappaB gene expression.
AB  - A Moringa oleifera seed lectin (MOSL) was purified by using chitin column with
      the molecular mass of 17+/-1kDa. The lectin agglutinated mouse, cow and human
      erythrocytes and the hemagglutination activity was inhibited by methyl-alpha-d
      mannopyranoside, methyl-beta-d-galactopyranoside, lactose and glucose. The lectin
      exhibited 100% hemagglutination activity at the pH range from 8.0 to 9.0 and
      temperature range from 30 to 60 degrees C. Additionally, the lectin gradually
      lost its activity in the presence of urea but the activity abolish completely
      when treated with EDTA. MOSL showed mild toxicity against brine shrimp nauplii
      with a LC50 value of 131.0MUg/ml. Antiproliferative activity was studied against
      Ehrlich ascites carcinoma (EAC) cells and 71.08% cell growth inhibition was
      observed in vitro at 200MUg/ml. The lectin was injected (i.p.) into EAC mice at
      the doses of 2.0 and 4.0mg/kg/day for five consecutive days and 25.38% and 55% of
      cell growth inhibition was observed, respectively. MOSL caused the cell cycle
      arrest at G2/M phase as determined by FACS flow cytometry. The cell growth
      inhibition was due to the induction of apoptosis in the EAC cells which was
      confirmed by cell morphological study, caspase-3 inhibitor and activation of Bak
      and suppression of Bcl-2 and NF-kappaB genes expression.

PMID- 29037872
TI  - Preparation and characterization of microencapsulated DwPT trivalent vaccine
      using water soluble chitosan and its in-vitro and in-vivo immunological
      properties.
AB  - The paper explained the microencapsulation of three different antigenic materials
      viz. Diphtheria toxoid (DT), whole cell pertussis antigens (PT and FHA) and
      tetanus toxoid (TT) by coacervation method using water soluble chitosan as a
      polymer crosslinked by vanillin/TPP co-crosslinkers for the development of oral
      trivalent DwPT vaccine. Instrumental characterization of chitosan microspheres
      suggested specific interaction with vanillin/TPP, higher thermal stability,
      amorphous nature, spherical morphology with size less than 2MUm along with
      positive charge density offering mucoadhesive properties. Furthermore, PT and FHA
      showed higher encapsulation up to 94% followed by TT and DT. Cumulative release
      rate of DT was (68.47%), TT (73.67%), PT (43%) and FHA (53%). Release kinetics
      interpreted using DD solver program, indicated protein release followed first
      order kinetics and obeyed Korsmeyer-peppas model, stating fickian diffusion
      relates to diffusion, erosion and controlled release rate of the encapsulated
      toxoids. Application of formulations on caco-2 cell line showed negligible
      cytotoxic effect and efficient uptake of FITC labelled microspheres. The obtained
      in-vivo results suggests that the final trivalent DwPT formulation were having
      successful elicitation of both systemic (IgG) and mucosal (sIgA) immune response
      in balb/c mice. Overall studies indicated that DwPT formulation could be a
      suitable alternative to available injectable DaPT vaccine.

PMID- 29037873
TI  - Cross-linked ovalbumin catalyzed by polyphenol oxidase: Preparation, structure
      and potential allergenicity.
AB  - Ovalbumin (OVA) is described as one of the major allergens in hen's egg, and it
      is the most abundant protein in egg white. Enzyme-mediated covalent cross-linking
      of food proteins, can influence their structure and allergenicity. The aim of
      this study was to investigate the potential of polyphenol oxidase from Agaricus
      bisporus to cross-link OVA (CL-OVA) in the presence or absence of caffeic acid,
      followed by characterizing the structure and allergenicity of CL-OVA. A single
      factor experiment was designed to assess the optimum conditions for cross-linking
      of OVA by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Under the
      optimal conditions, structural changes in OVA were analyzed by circular
      dichroism, ultraviolet and fluorescence spectra. It was shown that CL-OVA became
      unordered and unfolded, and more tyrosine and tryptophan residues and hydrophobic
      groups were exposed onto the surface of molecules when compared to the native
      OVA. Enzyme-linked immunosorbent assay indicated that IgG and IgE binding
      abilities to OVA significantly reduced after cross-linking. All the findings
      demonstrated that enzymatic cross-linking in the presence of caffeic acid as a
      mediator may decrease the antigenicity and potential allergenicity, and the
      changes of the modified OVA were most likely a consequence of some changes or
      adjustment in the local conformation of OVA and the epitopes of OVA by cross
      linking.

PMID- 29037874
TI  - Preparation and optimization of chitosan-gelatin films for sustained delivery of
      lupeol for wound healing.
AB  - Lupeol entrapped chitosan-gelatin hydrogel (LCGH) films were prepared by solution
      cast method by blending chitosan and gelatin solution using glycerol as
      plasticizer, followed by crosslinking with glutaraldehyde. LCGH films were
      characterized by scanning electron microscopy (SEM), Fourier transform infrared
      spectroscopy (FTIR), differential scanning calorimetry (DSC), equilibrium water
      content (EWC), Water vapor transmission rate (WVTR) and in vitro release studies.
      SEM confirmed presence of the uniform porous network of both blank and LCGH
      films. The incorporation of lupeol in hydrogel was confirmed FTIR and DSC. The
      LCGH film was smooth, flexible, non-brittle and showed excellent swelling
      ability. EWC (85.40%) and WVTR (2228+/-31.8) met the condition of ideal wound
      dressing. The biological activity of lupeol was assessed by antioxidant and
      antibacterial assay. Antioxidant assay confirmed that lupeol and LCGH film have
      excellent antioxidant properties by scavenging both radicals at steady increasing
      rate which increases with time due to steady release of lupeol. Antibacterial
      activity of lupeol in LCGH film was found to be retained as assessed by disc
      diffusion method. Cell viability was evaluated by MTT assay with NIH/3T3
      fibroblast cells. The MTT assay showed that the CGH film evidently offered
      acceptable cell viability and non-toxicity. These observations depicted that
      chitosan/gelatin hydrogel film can be an ideal delivery system for sustained
      released of lupeol and LCGH film for enhanced wound healing.

PMID- 29037875
TI  - Interplay between CedA, rpoB and double stranded DNA: A step towards
      understanding CedA mediated cell division in E. coli.
AB  - Cell division is compromised in DnaAcos mutant E. coli cells due to chromosome
      over-replication. In these cells, CedA acts as a regulatory protein and initiates
      cell division by a hitherto unknown mechanism. CedA, a double stranded DNA
      binding protein, interacts with various subunits of RNA polymerase complex,
      including rpoB. To reveal how this concert between CedA, rpoB and DNA brings
      about cell division in E. coli, we performed biophysical and in silico analysis
      and obtained mechanistic insights. Interaction between CedA and rpoB was shown by
      circular dichroism spectrometry and in silico docking experiments. Further, CedA
      and rpoB were allowed to interact individually to a selected DNA and their
      binding was monitored by fluorescence spectroscopy. The binding constants of
      these interactions as determined by BioLayer Interferometry clearly show that
      rpoB binds to DNA with higher affinity (KD2=<1.0E-12M) as compared to CedA
      (KD2=9.58E-09M). These findings were supported by docking analysis where 12
      intermolecular H-bonds were formed in rpoB-DNA complex as compared to 4 in CedA
      DNA complex. Based on our data we propose that in E. coli cells chromosome over
      replication signals CedA to recruit rpoB to specific DNA site(s), which initiates
      transcription of cell division regulatory elements.

PMID- 29037876
TI  - Photobiomodulation of local alterations induced by BthTX-I, a phospholipase A2
      myotoxin from Bothrops jararacussu snake venom: In vivo and in vitro evaluation.
AB  - This report describes the effect of photobiomodulation (PBM) on edema formation,
      leukocyte influx, prostaglandin E2 (PGE2) biosynthesis and cytotoxicity caused by
      bothropstoxin-I (BthTX-I), a phospholipase A2 (PLA2) homologue isolated from
      Bothrops jararacussu snake venom. Swiss mice or C2C12 cells were irradiated with
      low-level laser (LLL) at 685nm wavelength, an energy density of 4.6J/cm2 and an
      irradiation time of 13s. To evaluate the effect on edema formation and leukocyte
      influx, LLL was applied to the site of inoculation 30min and 3h post-injection.
      C2C12 cells were exposed to BthTX-I and immediately irradiated. PBM significantly
      reduced paw edema formation, peritoneal leukocyte influx and PGE2 synthesis, but
      increased the viability of C2C12 muscle cells after BthTX-I incubation. These
      findings demonstrate that PBM attenuated the inflammatory events induced by BthTX
      I. The attenuation of PGE2 synthesis could be an important factor in the reduced
      inflammatory response caused by laser irradiation. The ability of LLL irradiation
      to protect muscle cells against the deleterious effects of BthTX-I may indicate
      preservation of the plasma membrane.

PMID- 29037877
TI  - Unbreakable? An analysis of the fragility of randomized trials that support
      diabetes treatment guidelines.
AB  - AIMS: To analyze the robustness of randomized controlled trials (RCTs) referenced
      in the American Diabetes Association's Standards of Medical Care in Diabetes-2017
      using the Fragility Index (FI) and Fragility Quotient (FQ). METHODS: We performed
      a systematic survey of all RCTs referenced in the Standards of Medical Care in
      Diabetes-2017. One investigator screened for trials and then recorded data from
      them, including sample size per group, event rate per group, and the dichotomous
      outcome analyzed by trialists. The FI and FQ for each outcome were calculated.
      Outcomes were then surveyed to determine whether the outcome used for analysis
      aligned with the guideline recommendation. RESULTS: Thirty-five RCTs were
      included in this study. Thirty-three of 35 (94%) FIs were based on the trial
      outcomes referenced in the clinical practice guideline. The median sample size
      was 2548 participants ([IQR], 522-6946). The median total number of events for
      each outcome was 403 (IQR, 86-969). Nineteen (54%) P Values were below 0.05, 8
      (22.4%) were below 0.01. The median FI for all trials was 16 (IQR, 4-29). The
      median FQ was 0.007 (IQR, 0.003-0.014). FI was not related to risk of bias or
      Science Citation Index but was significantly correlated with sample size (for
      significant trials; r=0.77, P < .001, for neutral trials; r=0.76, P < .001).
      CONCLUSIONS: We found that the robustness of RCTs varied, but on the whole were
      not robust in nature. Most trials demonstrated a modest FI and FQ. As a result,
      conclusions drawn from these trials should take this information into account.

PMID- 29037878
TI  - Risperidone ameliorates cognitive deficits, promotes hippocampal proliferation,
      and enhances Notch signaling in a murine model of schizophrenia.
AB  - Antipsychotic agents have been reported to promote hippocampal neurogenesis and
      improve cognitive deficits; yet, the molecular mechanisms underlying these
      actions remain unclear. In the present study, we used a murine model of
      schizophrenia induced by 5-day intraperitoneal injection with the non-competitive
      N-methyl-d-aspartate receptor antagonist MK801 (0.3mg/kg/day) to assess cognitive
      behavioral deficits, changes in Notch signaling, and cellular proliferation in
      the hippocampus of adult male C57BL/6 mice after 2-week administration of
      risperidone (Rip, 0.2mg/kg/day) or vehicle. We then utilized in vivo stereotaxic
      injections of a lentivirus expressing a short hairpin RNA (shRNA) for Notch1 into
      the dentate gyrus to examine the role of Notch1 in the observed actions of Rip.
      We found that Rip ameliorated cognitive deficits and restored cell proliferation
      in MK801-treated mice in a manner associated with the up-regulation of Notch
      signaling molecules, including Notch1, Hes1, and Hes5. Moreover, these effects
      were abolished by pretreatment with Notch1 shRNA. Our results suggest that the
      ability of Rip to improve cognitive function in schizophrenia is mediated in part
      by Notch signaling.

PMID- 29037879
TI  - A risk-based approach for assessing the recycling potential of an alkaline waste
      material as road sub-base filler material.
AB  - In this work we present an integrated risk-based approach that can be used to
      evaluate the recycling potential of an alkaline waste material such as
      incineration bottom ash (BA) as unbound material for road sub-base construction.
      This approach, which is aimed at assessing potential risks to the groundwater
      resource (in terms of drinking water quality) and human health associated to the
      leaching of contaminants from the BA, couples the results of leaching tests for
      the estimation of source concentrations with the fate and transport models
      usually adopted in risk assessment procedures. The effects of weathering and of
      the type of leaching test employed to evaluate eluate concentrations were
      assessed by carrying out different simulations using the results of laboratory
      leaching tests. Specifically, pH-dependence and column percolation leaching tests
      were performed on freshly collected and 1-year naturally weathered BA samples
      produced from a grate-fired incineration plant treating Refuse Derived Fuel
      (RDF). To evaluate a broad span of possible scenario conditions, a Monte Carlo
      analysis was performed running 5000 simulations, randomly varying the input
      parameters within the ranges expected in the field. In nearly all the simulated
      conditions, the concentrations of contaminants in the groundwater for the
      specific type of BA tested in this work were well below EU and WHO drinking water
      quality criteria. Nevertheless, some caution should be paid in the case of the
      establishment of acidic conditions in the field since in this case the
      concentration of some elements (i.e. Al, Pb and Zn) is expected to exceed
      threshold values. In terms of risks to human health, for the considered
      utilization scenario the probability of exceeding the acceptable reference dose
      for water ingestion was usually less than 1% (except for Cr and Pb for which the
      probability was lower than 3.5% and 7%, respectively).

PMID- 29037880
TI  - Monitoring of microbial communities in anaerobic digestion sludge for biogas
      optimisation.
AB  - This study characterised and compared the microbial communities of anaerobic
      digestion (AD) sludge using three different methods - (1) Clone library; (2)
      Pyrosequencing; and (3) Terminal restriction fragment length polymorphism (T
      RFLP). Although high-throughput sequencing techniques are becoming increasingly
      popular and affordable, the reliance of such techniques for frequent monitoring
      of microbial communities may be a financial burden for some. Furthermore, the
      depth of microbial analysis revealed by high-throughput sequencing may not be
      required for monitoring purposes. This study aims to develop a rapid, reliable
      and economical approach for the monitoring of microbial communities in AD sludge.
      A combined approach where genetic information of sequences from clone library was
      used to assign phylogeny to T-RFs determined experimentally was developed in this
      study. In order to assess the effectiveness of the combined approach, microbial
      communities determined by the combined approach was compared to that
      characterised by pyrosequencing. Results showed that both pyrosequencing and
      clone library methods determined the dominant bacteria phyla to be
      Proteobacteria, Firmicutes, Bacteroidetes, and Thermotogae. Both methods also
      found that sludge A and B were predominantly dominated by acetogenic methanogens
      followed by hydrogenotrophic methanogens. The number of OTUs detected by T-RFLP
      was significantly lesser than that detected by the clone library. In this study,
      T-RFLP analysis identified majority of the dominant species of the archaeal
      consortia. However, many of the more highly diverse bacteria consortia were
      missed. Nevertheless, the combined approach developed in this study where clone
      sequences from the clone library were used to assign phylogeny to T-RFs
      determined experimentally managed to accurately predict the same dominant
      microbial groups for both sludge A and sludge B, as compared to the
      pyrosequencing results. Results showed that the combined approach of clone
      library and T-RFLP accurately predicted the dominant microbial groups and thus is
      a reliable and more economical way to monitor the evolution of microbial systems
      in AD sludge.

PMID- 29037881
TI  - Food waste behaviour at the household level: A conceptual framework.
AB  - One-third of the world produced food is wasted according to FAO (2011). The aim
      of this paper is to have an in-depth analysis of consumers' behaviours regarding
      food waste in Egypt. A conceptual framework is developed that brings many factors
      considered in the recent literature in one model to be tested using structural
      equation modeling. Results indicate that the incorporated factors were found
      statistically significant. Additionally, the individual's perception about food
      waste was related with food quantities wasted at the household level. The
      findings suggest considering these factors when developing new policies and
      campaigns for food waste reduction.

PMID- 29037882
TI  - Stabbing plus cupping: A less invasive but more powerful sucking approach for
      superficial abscesses.

PMID- 29037883
TI  - Letter to the editor on "Open versus closed lateral internal anal sphincterotomy
      in the management of chronic anal fissures: A prospective randomised study". Our
      results in the patients who undergone to secondary healing following the fissure
      tract excision for primary chronic anal fissure.

PMID- 29037884
TI  - Could post-thyroidectomy bleeding be the clue to modify the concept of
      postoperative drainage? A prospective randomized controlled study.
AB  - BACKGROUND/OBJECTIVE: To unveil the real effect of surgical drains on the
      outcomes of thyroidectomy for benign thyroid disorders. METHODS: A prospective
      randomized study was conducted at Abha Private Hospital, Saudi Arabia on 108
      patients suffered from benign thyroid disorders undergoing elective thyroidectomy
      from 1 August 2015 to 28 February 2017. Patients were allocated randomly into
      drainage group (A) and non-drainage group (B). The demographic data, operation
      (type and duration), postoperative complications, histopathological results and
      length of stay were assessed, documented and statistically verified to check its
      significance. RESULTS: A total of 108 patients were enrolled in the study; 94
      females and 14 males with mean age of 38.02 years, two patients developed
      hematoma (1.85%); one in each group and another two patients had seroma with no
      significant difference between both groups, the mean length of stay was
      significantly higher in group (A) (p = 0.001). CONCLUSION: This prospective study
      verified that routine drainage adds no significant advantage in the prevention of
      post-thyroidectomy bleeding, but it prolongs hospitalization. This aids in
      changing the concept from the "wide" use of drains into the "wise" use in
      selected patients with risk factors of bleeding.

PMID- 29037885
TI  - National trends and outcomes of cardiac arrest in opioid overdose.
AB  - AIM: To investigate the epidemiology and outcomes of cardiac arrests associated
      with opioid overdoses. Recent data suggest that drug overdoses are responsible
      for more deaths than motor vehicle crashes or firearms in the United States each
      year, with opioids being involved in majority of drug overdose deaths. Despite
      the potential for opioids to cause cardiac arrest, few studies have examined this
      association. PATIENTS AND METHODS: Using data from National (Nationwide)
      Inpatient Sample database from years 2000-2013, we identified hospitalizations
      with drug overdoses using ICD-9-CM codes. We further identified those with opioid
      overdose and those with cardiac arrest. We then assessed the proportion and
      trends of cardiac arrest and associated mortality in patients with opioid
      overdose. We also investigated if opioid overdose is an independent risk factor
      for cardiac arrest and mortality. RESULTS: Of 3,835,448 United States drug
      overdose hospitalizations, 16.4% were associated with prescription opioid
      overdose and 2.3% with heroin overdose. Cardiac arrest was most common with
      heroin overdose, followed by prescription opioids and least common in non-opioid
      overdose (3.8% vs 1.4% vs 0.6%; p<0.001). Heroin overdoses have seen the greatest
      increase in rate of cardiac arrests. Both prescription opioids and heroin
      overdose were independent risk factors for cardiac arrest and mortality in these
      patients. CONCLUSIONS: Cardiac arrest is more common in patients with opioid
      overdoses in comparison to non-opioid overdoses. The rate of cardiac arrest is
      increasing disproportionately in patients with opioid overdoses. Opioid overdoses
      are independent risk factors for both cardiac arrest and mortality in patients
      with overdoses.

PMID- 29037886
TI  - Comparative effectiveness of antiarrhythmics for out-of-hospital cardiac arrest:
      A systematic review and network meta-analysis.
AB  - BACKGROUND: Despite their wide use in the prehospital setting, randomized control
      trials (RCTs) have failed to demonstrate that any antiarrhythmic agent improves
      survival to hospital discharge following out-of-hospital cardiac arrest.
      OBJECTIVE: To assess the use of antiarrhythmic drugs for patients experiencing
      out-of-hospital cardiac arrest (OHCA). METHODS: Electronic searches of Medline,
      EMBASE and Cochrane Central Register of Controlled Trials were conducted and
      reference lists were hand-searched. Randomized controlled trials (RCTs)
      investigating the use of antiarrhythmic agents administered during resuscitation
      for adult (>=18years) patients suffering non-traumatic OHCA were included. Direct
      and indirect evidence were combined in a network meta-analysis (NMA) using a
      frequentist approach with fixed-effects models and reported as relative risks
      (RR) with 95% confidence intervals (CIs). For each pairwise comparison, the
      certainty of direct, indirect, and network evidence was assessed using the GRADE
      approach. RESULTS: 8 RCTs involving 4464 patients were combined to compare the
      effectiveness of 5 antiarrhythmic agents and placebo administered during
      resuscitation following OHCA. Lidocaine was associated with a statistically
      significant increase in ROSC compared to placebo (1.15; 95% CI: 1.03-1.28) and
      was also superior to bretylium (1.61; 95% CI: 1.00-2.60) for ROSC. When compared
      to placebo, both amiodarone (1.18; 95% CI: 1.08-1.30) and lidocaine (1.18; 95%
      CI: 1.07-1.30) were associated with a statistically significant increase in
      survival to hospital admission. However, no antiarrhythmic was statistically more
      effective than placebo for survival to hospital discharge or neurologically
      intact survival, and no antiarrhythmic was convincingly superior to any other for
      any outcome. CONCLUSIONS: Amiodarone and lidocaine were the only agents
      associated with improved survival to hospital admission in the NMA. For the
      outcomes most important to patients, survival to hospital discharge and
      neurologically intact survival, no antiarrhythmic was convincingly superior to
      any other or to placebo.

PMID- 29037887
TI  - Depression and related risk factors among patients with type 2 diabetes mellitus,
      Jazan area, KSA: A cross-sectional study.
AB  - PURPOSE: To determine the prevalence of depression and related risk factors among
      type 2 diabetes mellitus patients (T2DM) in Jazan area, Saudi Arabia. METHOD: A
      cross sectional, self-administered questionnaire study was conducted among T2DM
      patients in Jazan area, Saudi Arabia. A total of 385 patients were selected at
      randomly. The Patient Health Questionnaire (PHQ-9) was utilized to measure
      symptoms and signs of depression. RESULTS: The overall prevalence of depression
      among T2DM patients was 37.6%. Of them, 24.2% were mildly depressed, 9.6% were
      moderately severely depressed, and 4.2% were severely depression. Significant
      predictors of depression include the presence of diabetic foot (P=0.000), cardio
      vascular diseases (P=0.000), eye complication (P=0.073), and erectile dysfunction
      (P=0.090). The prevalence of depression was not significantly associated with the
      age (P=0.375) and gender (P=0.374). Similarly no association was found with
      duration of diabetes (P=0.475) and HbA1c (P=0.555). CONCLUSION: The study
      revealed that diabetes complications are strong predictors of the rate of
      depression among T2DM patients. Therefore, early depression screening is needed
      to improve the quality of life of diabetic patients.

PMID- 29037888
TI  - Preferred reporting items for overviews of systematic reviews including harms
      checklist: a pilot tool to be used for balanced reporting of benefits and harms.
AB  - OBJECTIVES: An overview of systematic reviews (OoSRs) is a study designed to
      synthesize multiple evidence from existing systematic reviews on a specific
      domain. The aim of this paper was to offer a pilot version checklist with
      Preferred Reporting Items for OoSRs (PRIO-harms) to promote a more balanced
      reporting of benefits and harms in OoSRs of health care interventions. STUDY
      DESIGN AND SETTING: The included items were developed by combining key features
      from health care OoSRs designs with recommendations from statements of other
      relevant checklists and pertinent methodological review articles. Two raters
      independently used the PRIO-harms checklist to assess a sample of 20 OoSRs.
      RESULTS: The PRIO-harms tool consists of a 27-item (56 (sub-)items in total)
      checklist and is accompanied by a five-stage process flow diagram
      (identification, screening, eligibility, inclusion, and separation of relevant
      studies). The mean interrater reliability (Gwet's AC1 statistic) between
      reviewers was 0.90 (95% confidence interval: 0.88, 0.92) indicating a very good
      agreement. CONCLUSION: The PRIO-harms tool can be used in every OoSRs that
      addresses health care interventions. This instrument will assist overview authors
      to improve completeness and transparency of research reporting with emphasis on
      harms. However, it might benefit from critical review and further validation from
      experts and research teams that produce OoSRs.

PMID- 29037889
TI  - Optimising the emergency to ward handover process: A mixed methods study.
AB  - BACKGROUND: The effective handover of patient health data from the emergency
      department to other hospital units is integral for the continuity of patient
      care. Yet no handover process has been identified as superior to others within
      this context. METHODS: This study within a regional Australian hospital employed
      mixed methods approach including focus groups and key stakeholder consultation to
      develop a handover form appropriate for patient transfer from the emergency
      department to a variety of clinical areas. Paper-based surveys and audits were
      then employed to evaluate the implementation and understand staff perceptions of
      the form. RESULTS: The implementation of a patient handover form within the
      emergency setting was well received. Participants indicated that the form is
      clear, well designed and easy to navigate. It provided prompts to standardise
      their clinical handover and increased their accountability and responsibility
      within this process. CONCLUSIONS: To deliver an optimal nursing handover from the
      emergency department to various wards handovers should be structured and provide
      standardised content. The positive reception and use of this form provides
      evidence that a structured handover process can ensure standardisation of
      emergency department to ward nursing handovers.

PMID- 29037890
TI  - Double-Expressor Lymphoma Is Associated with Poor Outcomes after Allogeneic
      Hematopoietic Cell Transplantation.
AB  - Double-expressor lymphoma (DEL) is a diffuse large B cell lymphoma that exhibits
      co-expression of MYC and BCL2 proteins by immunohistochemistry. Patients with
      double-expressor lymphoma have a poor prognosis after standard chemoimmunotherapy
      or after high-dose chemotherapy with autologous transplantation, but the
      prognostic impact of DEL after allogeneic hematopoietic cell transplantation has
      not been well characterized. We retrospectively analyzed 60 consecutive patients
      with de novo diffuse large B cell lymphoma or transformed follicular lymphoma who
      underwent allogeneic transplantation at our center and had available
      immunohistochemistry data. Thirty-seven patients (62%) had DEL. The 2-year
      progression-free and overall survival rates were lower in patients with DEL than
      in those without DEL (20% versus 78%; overall P <.001 and 46% versus 77%; overall
      P = .016, respectively). The cumulative incidence of disease progression at 2
      years was higher in patients with DEL (60% versus 13%; overall P = .005). The
      cumulative incidence of nonrelapse mortality did not differ statistically in the
      2 groups. Even in patients with DEL and chemosensitive disease at
      transplantation, the 2-year progression-free survival rate was only 27% due to
      early disease progression. Multivariate analysis showed associations between DEL
      and increased risks of progression-free survival events (hazard ratio [HR], 4.58;
      95% confidence interval [CI], 2.07-10.2; P <.001), overall mortality (HR, 2.29;
      95% CI, 1.03-5.09; P = .042) and disease progression (HR, 3.60; 95% CI, 1.38
      9.44; P = .009). Patients with DEL had poor outcomes after allogeneic
      transplantation. Innovative strategies are needed to improve outcomes in this
      population.

PMID- 29037891
TI  - Chemotherapy-Based Stem Cell Mobilization Does Not Result in Significant
      Paraprotein Reduction in Myeloma Patients in the Era of Novel Induction Regimens.
AB  - Novel induction agents markedly improved remission rates in multiple myeloma
      (MM), and the continued use of chemotherapy for CD34+ stem cell mobilization
      (SCM) has been questioned. We examined the additional effect of chemotherapy in
      SCM regarding remission status/morbidity. We reviewed 236 consecutive MM patients
      (aged 36 to 75 years) with first autologous stem cell transplantation from
      January 2009 to March 2016 after chemotherapy-based SCM. Responses were measured
      by changes in intact Ig and free light chain levels before and after
      chemomobilization (International Myeloma Working Group [IMWG] criteria). Most
      patients (225/236, 95.3%) received novel induction regimens, which were
      bortezomib-based (n = 223) and/or lenalidomide-based (n = 19). Most patients
      (170/190, 89.5%) achieved at least partial remission postinduction and pre-SCM.
      Stem cells were mobilized with granulocyte colony-stimulating factor and
      cyclophosphamide-based (212/227, 93.4%) or etoposide-based (15/227, 6.6%)
      regimens. There were insignificant changes in serum Ig and free light chain
      levels before and after chemomobilization either in the whole cohort or
      subgroups. Significant improvements of the IMWG remission status were documented
      in only 7 of 236 patients (3.0%). Sixty-seven patients (28.4%) developed
      chemotherapy-related complications (neutropenic fever, sepsis, and others),
      resulting in 9 hospitalizations (3.8%). Our study suggests that although causing
      significant morbidity, chemotherapy-based mobilization fails to improve remission
      status. The value of incorporating additional chemotherapy for SCM is thus not
      evident.

PMID- 29037892
TI  - Hybrid-spheroids incorporating ECM like engineered fragmented fibers potentiate
      stem cell function by improved cell/cell and cell/ECM interactions.
AB  - : Extracellular matrix (ECM) microenvironment is critical for the viability,
      stemness, and differentiation of stem cells. In this study, we developed hybrid
      spheroids of human turbinate mesenchymal stem cells (hTMSCs) by using
      extracellular matrix (ECM) mimicking fragmented fibers (FFs) for improvement of
      the viability and functions of hTMSCs. We prepared FFs with average size of 68.26
      um by partial aminolysis of poly L-lactide (PLLA) fibrous sheet (FS), which was
      coated with polydopamine for improved cell adhesion. The proliferation of hTMSCs
      within the hybrid-spheroids mixed with fragmented fibers was significantly
      increased as compared to that from the cell-only group. Cells and fragmented
      fibers were homogenously distributed with the presence of pore like empty spaces
      in the structure. LOX-1 staining revealed that the hybrid-spheroids improved the
      cell viability, which was potentially due to enhanced transport of oxygen through
      void space generated by engineered ECM. Transmission electron microscopy (TEM)
      analysis confirmed that cells within the hybrid-spheroid formed strong cell
      junctions and contacts with fragmented fibers. The expression of cell junction
      proteins including connexin 43 and E-cadherin was significantly upregulated in
      hybrid-spheroids by 16.53 +/- 0.04 and 28.26 +/- 0.11-fold greater than that from
      cell-only group. Similarly, expression of integrin alpha2, alpha5, and beta1 was
      significantly enhanced at the same group by 25.72 +/- 0.13, 27.48 +/- 0.49, and
      592.78 +/- 0.06-fold, respectively. In addition, stemness markers including Oct
      4, Nanog, and Sox2 were significantly upregulated in hybrid-spheroids by 96.56 +/
      0.06, 158.95 +/- 0.06, and 115.46 +/- 0.47-fold, respectively, relative to the
      cell-only group. Additionally, hTMSCs within the hybrid-spheroids showed
      significantly greater osteogenic differentiation under osteogenic media
      conditions. Taken together, our hybrid-spheroids can be an ideal approach for
      stem cell expansion and serve as a potential carrier for bone regeneration.
      STATEMENT OF SIGNIFICANCE: Cells are spatially arranged within extracellular
      matrix (ECM) and cell/ECM interactions are crucial for cellular functions. Here,
      we developed a hybrid-spheroid system incorporating engineered ECM prepared from
      fragmented electrospun fibers to tune stem cell functions. Conventionally
      prepared cell spheroids with large diameters (>200 um) is often prone to hypoxia.
      In contrast, the hybrid-spheroids significantly enhanced viability and
      proliferation of human turbinate mesenchymal stem cells (hTMSCs) as compared to
      spheroid prepared from cell only. Under these conditions, the presence of
      fragmented fibers also improved maintenance of stemness of hTMSCs for longer time
      cultured in growth media and demonstrated significantly greater osteogenic
      differentiation under osteogenic media conditions. Thus, the hybrid-spheroids can
      be used as a delivery carrier for stem cell based therapy or a 3D culture model
      for in vitro assay.

PMID- 29037893
TI  - Gelatin promotes rapid restoration of the blood brain barrier after acute brain
      injury.
AB  - : Gelatin coating of brain implants is known to provide considerable benefits in
      terms of reduced inflammatory sequalae and long-term neuroprotective effects.
      However, the mechanisms for gelatin's protective role in brain injury are still
      unknown. To address this question, cellular and molecular markers were studied
      with quantitative immunohistochemical microscopy at acute (<2hours, 1, 3days),
      intermediate (1-2 weeks) and long-term time points (6 weeks) after transient
      insertion of stainless steel needles into female rat cortex cerebri with or
      without gelatin coating. Compared to non-coated controls, injuries caused by
      gelatin coated needles showed a significantly faster resolution of post-stab
      bleeding/leakage and differential effects on different groups of microglia cells.
      While similar levels of matrix metalloproteinase (MMP-2 and MMP-9, two
      gelatinases) was found for coated and noncoated needle stabs during the first
      week, markedly increased levels of both MMPs was seen for gelatin-coated but not
      non-coated needle stabs after 2weeks. Neuronal populations and activated
      astrocytes were largely unaffected. In conclusion, the beneficial effects of
      gelatin may be the combined results of faster healing of the blood brain barrier
      curtailing leakage of blood borne molecules/cells into brain parenchyma and to a
      modulation of the microglial population response favoring restitution of the
      injured tissue. These findings present an important therapeutic potential for
      gelatin coatings in various disease, injury and surgical conditions. STATEMENT OF
      SIGNIFICANCE: The neural interfaces field holds great promise to enable
      elucidation of neural information processing and to develop new implantable
      devices for stimulation based therapy. Currently, this field is struggling to
      find solutions for reducing tissue reactions to implanted micro and
      nanotechnology. Prior studies have recently shown that gelatin coatings lower
      activation of digestive microglia and mitigate the ubiquitous loss of neurons
      adjacent to implanted probes, both of which impede implant function. The
      underlying mechanisms remain to be elucidated, however. Our findings demonstrate
      for the first time that gelatin has a significant effect on the BBB by promoting
      rapid restoration of integrity after injury. Moreover, gelatin alters microglia
      phenotypes and modulates gelatinase activity for up to 2weeks favoring anti
      inflammation and restoration of the tissue. Given the key importance of the BBB
      for normal brain functions, we believe our findings have substantial significance
      and will be highly interesting to researchers in the biomaterial field.

PMID- 29037894
TI  - Indentation mapping revealed poroelastic, but not viscoelastic, properties
      spanning native zonal articular cartilage.
AB  - : Osteoarthrosis is a debilitating disease affecting millions, yet engineering
      materials for cartilage regeneration has proven difficult because of the complex
      microstructure of this tissue. Articular cartilage, like many biological tissues,
      produces a time-dependent response to mechanical load that is critical to cell's
      physiological function in part due to solid and fluid phase interactions and
      property variations across multiple length scales. Recreating the time-dependent
      strain and fluid flow may be critical for successfully engineering replacement
      tissues but thus far has largely been neglected. Here, microindentation is used
      to accomplish three objectives: (1) quantify a material's time-dependent
      mechanical response, (2) map material properties at a cellular relevant length
      scale throughout zonal articular cartilage and (3) elucidate the underlying
      viscoelastic, poroelastic, and nonlinear poroelastic causes of deformation in
      articular cartilage. Untreated and trypsin-treated cartilage was sectioned
      perpendicular to the articular surface and indentation was used to evaluate
      properties throughout zonal cartilage on the cut surface. The experimental
      results demonstrated that within all cartilage zones, the mechanical response was
      well represented by a model assuming nonlinear biphasic behavior and did not
      follow conventional viscoelastic or linear poroelastic models. Additionally, 10%
      (w/w) agarose was tested and, as anticipated, behaved as a linear poroelastic
      material. The approach outlined here provides a method, applicable to many
      tissues and biomaterials, which reveals and quantifies the underlying causes of
      time-dependent deformation, elucidates key aspects of material structure and
      function, and that can be used to provide important inputs for computational
      models and targets for tissue engineering. STATEMENT OF SIGNIFICANCE: Elucidating
      the time-dependent mechanical behavior of cartilage, and other biological
      materials, is critical to adequately recapitulate native mechanosensory cues for
      cells. We used microindentation to map the time-dependent properties of untreated
      and trypsin treated cartilage throughout each cartilage zone. Unlike conventional
      approaches that combine viscoelastic and poroelastic behaviors into a single
      framework, we deconvoluted the mechanical response into separate contributions to
      time-dependent behavior. Poroelastic effects in all cartilage zones dominated the
      time-dependent behavior of articular cartilage, and a model that incorporates
      tension-compression nonlinearity best represented cartilage mechanical behavior.
      These results can be used to assess the success of regeneration and repair
      approaches, as design targets for tissue engineering, and for development of
      accurate computational models.

PMID- 29037895
TI  - In situ depot formation of anti-HIV fusion-inhibitor peptide in recombinant
      protein polymer hydrogel.
AB  - : Most peptide drugs have short half-lives, necessitating frequent injections
      that may induce skin sensitivity reactions; therefore, versatile prolonged
      release delivery platforms are urgently needed. Here, we focused on an
      oxidatively and thermally responsive recombinant elastin-like polypeptide with
      periodic cysteine residues (cELP), which can rapidly and reversibly form a
      disulfide cross-linked network in which peptide can be physically incorporated.
      As a model for proof of concept, we used enfuvirtide, an antiretroviral fusion
      inhibitor peptide approved for treatment of human immunodeficiency virus (HIV)
      infection. cELP was mixed with enfuvirtide and a small amount of hydrogen
      peroxide (to promote cross-linking), and the soluble mixture was injected
      subcutaneously. The oxidative cross-linking generates a network structure,
      causing the mixture to form a hydrogel in situ that serves as an enfuvirtide
      depot. We fabricated a series of enfuvirtide-containing hydrogels and examined
      their stability, enfuvirtide-releasing profile and anti-HIV potency in vitro.
      Among them, hydrophobic cELP hydrogel provided effective concentrations of
      enfuvirtide in blood of rats for up to 8 h, and the initial concentration peak
      was suppressed compared with that after injection of enfuvirtide alone. cELP
      hydrogels should be readily adaptable as platforms to provide effective depot
      systems for delivery of other anti-HIV peptides besides enfuvirtide. STATEMENT OF
      SIGNIFICANCE: In this paper, we present an anti-HIV peptide delivery system using
      oxidatively and thermally responsive polypeptides that contain multiple periodic
      cysteine residues as an injectable biomaterial capable of in situ self-gelation,
      and we demonstrate its utility as an injectable depot capable of sustained
      release of anti-HIV peptides. The novelty of this work stems from the platform
      employed to provide the depot encapsulating the peptide drugs (without chemical
      conjugation), which consists of rationally designed, genetically engineered
      polypeptides that enable the release rate of the peptide drugs to be precisely
      controlled.

PMID- 29037896
TI  - Manipulation of the response of human endothelial colony-forming cells by focal
      adhesion assembly using gradient nanopattern plates.
AB  - : Nanotopography plays a pivotal role in the regulation of cellular responses.
      Nonetheless, little is known about how the gradient size of nanostructural
      stimuli alters the responses of endothelial progenitor cells without chemical
      factors. Herein, the fabrication of gradient nanopattern plates intended to mimic
      microenvironment nanotopography is described. The gradient nanopattern plates
      consist of nanopillars of increasing diameter ranges [120-200 nm (GP 120/200),
      200-280 nm (GP 200/280), and 280-360 nm (GP 280/360)] that were used to screen
      the responses of human endothelial colony-forming cells (hECFCs). Nanopillars
      with a smaller nanopillar diameter caused the cell area and perimeter of hECFCs
      to decrease and their filopodial outgrowth to increase. The structure of vinculin
      (a focal adhesion marker in hECFCs) was also modulated by nanostructural stimuli
      of the gradient nanopattern plates. Moreover, Rho-associated protein kinase
      (ROCK) gene expression was significantly higher in hECFCs cultured on GP 120/200
      than in those on flat plates (no nanopillars), and ROCK suppression impaired the
      nanostructural-stimuli-induced vinculin assembly. These results suggest that the
      gradient nanopattern plates generate size-specific nanostructural stimuli
      suitable for manipulation of the response of hECFCs, in a process dependent on
      ROCK signaling. This is the first evidence of size-specific nanostructure-sensing
      behavior of hECFCs. SIGNIFICANCE: Nano feature surfaces are of growing interest
      as materials for a controlled response of various cells. In this study, we
      successfully fabricated gradient nanopattern plates to manipulate the response of
      blood-derived hECFCs without any chemical stimulation. Interestingly, we find
      that the sensitive nanopillar size for manipulation of hECFCs is range between
      120 nm and 200 nm, which decreased the area and increased the filopodial
      outgrowth of hECFCs. Furthermore, we only modulate the nanopillar size to
      increase ROCK expression can be an attractive method for modulating the
      cytoskeletal integrity and focal adhesion of hECFCs.

PMID- 29037897
TI  - Overcoming multiple gastrointestinal barriers by bilayer modified hollow
      mesoporous silica nanocarriers.
AB  - : Oral administration of nanocarriers remains a significant challenge in the
      pharmaceutical sciences. The nanocarriers must efficiently overcome multiple
      gastrointestinal barriers including the harsh gastrointestinal environment, the
      mucosal layer, and the epithelium. Neutral hydrophilic surfaces are reportedly
      necessary for mucus permeation, but hydrophobic and cationic surfaces are
      important for efficient epithelial absorption. To accommodate these conflicting
      surface property requirements, we developed a strategy to modify nanocarrier
      surfaces with cationic cell-penetrating peptides (CPP) concealed by a hydrophilic
      succinylated casein (SCN) layer. SCN is a mucus-inert natural material
      specifically degraded in the intestine, thus protecting nanocarriers from the
      harsh gastric environment, facilitating their mucus permeation, and inducing
      exposure of CPPs after degradation for further effective transepithelial
      transport. Quantum dots doped hollow silica nanoparticles (HSQN) with a diameter
      around 180 nm was used as the nanocarrier and demonstrated as high as 50% loading
      efficacy of paclitaxel, a model drug with poor solubility and permeability. The
      dual layer modification strategy prevented premature drug leakage in stomach and
      maintained high mucus permeation (the trajectory spanned 9-fold larger area than
      single CPP modification). After intestinal degradation of SCN by trypsin, these
      nanocarriers exhibited strong interaction with epithelial membranes and a 5-fold
      increase in cellular uptake. Significant transepithelial transport and intestinal
      distribution were also observed for this dual-modified formulation. A
      pharmacokinetics study on the paclitaxel-loaded nanocarrier found 40% absolute
      bioavailability and 7.8-fold higher AUC compared to oral Taxol(r). Compared with
      single CPP modified nanocarriers, our formulation showed increased in vivo
      efficacy and tumor accumulation of the model drug with negligible intestinal
      toxicity. In summary, sequential modification with CPP and SCN layers on HSQN
      offers a potential strategy to overcome the multiple barriers of the
      gastrointestinal tract. STATEMENT OF SIGNIFICANCE: Oral administration of
      nanocarriers remains a big challenge due to the multiple gastrointestinal
      barriers. In order to achieve both strong mucus permeation and efficient
      epithelial absorption, we modified the surface of silica nanoparticles with two
      layers: cell penetrating peptide (CPP) layer and succinylated casein (SCN) layer.
      The newly developed nanoformulations are demonstrated to have the following
      advantages: 1) versatile carrier with easy preparation, 2) high drug loading
      especially for poor soluble molecules, 3) reduced drug leakage in the stomach, 4)
      effective mucus penetration and transepithelial transport and 5) good
      biocompatibility, which in all indicate a great potential of this bilayer
      modification strategy to facilitate the oral delivery of therapeutic agents.

PMID- 29037898
TI  - Zika virus and autoimmunity. One-step forward.
AB  - Zika virus (ZIKV) infection has been associated with the development of Guillain
      Barre syndrome (GBS) and idiopathic thrombocytopenic purpura (ITP). Whether ZIKV
      infection is related to other autoimmune diseases is unknown. Therefore, an
      association study to evaluate rheumatic and thyroid autoimmunity in patients with
      ZIKV disease was conducted through a panel of 14 autoantibodies. In addition, a
      literature review on ZIKV, and GBS and ITP was performed. Our results disclosed a
      lack of association of rheumatoid and thyroid autoimmunity with ZIKV disease. A
      total of 272 cases of GBS related to ZIKV were retrieved from the literature, the
      majority of them being males (54.8%). Electrophysiological findings indicated
      acute inflammatory demyelinating polyneuropathy as the most frequent subphenotype
      (75.7%). Up to date, twenty-four cases of ITP in patients with ZIKV disease have
      been published. Although a few fatal cases have been observed, most of the
      reported patients responded well to immunomodulatory treatment. A review of the
      mechanisms incriminated into the development of autoimmune phenomenon in ZIKV
      disease indicates molecular mimicry as the most plausible one. Nevertheless, more
      research aimed at deciphering ZIKV disease pathogenesis and its relationship with
      autoimmunity is warranted.

PMID- 29037899
TI  - The management of first-line biologic therapy failures in rheumatoid arthritis:
      Current practice and future perspectives.
AB  - The introduction of biologic disease-modifying anti-rheumatic drugs (bDMARDs) has
      dramatically changed the management of rheumatoid arthritis (RA). However, in a
      real-life setting about 30-40% of bDMARD treated patients experience drug
      discontinuation because of either inefficacy or adverse events. According to
      international recommendations, to date the best strategy for managing first-line
      bDMARD failures has not been defined yet and available data (especially on TNF
      inhibitors [TNFis]) seem to drive toward a personalized approach for the
      individual patient. Some TNFi partial responders may benefit from optimization of
      concomitant methotrexate therapy or from switching to a different concomitant
      sDMARD such as leflunomide. Conversely, apart from infliximab, TNFi dose
      escalation seems to be poor efficacious and poor cost-effective compared with
      alternative strategies. Albeit counterintuitive, the use of a second TNFi after
      the failure of the first-one (cycling strategy) is supported by clear evidences
      and has become widespread in the 2000s as the result of the limited alternative
      options till the introduction of bDMARDs with a mechanism of action other than
      TNF blockade. Nowadays, the use of abatacept, rituximab, tocilizumab, or JAK
      inhibitors as second-line agent (swapping strategy) is strongly supported by RCTs
      and real-life experiences. In the absence of head-to-head trials directly
      comparing these two strategies, meta-analyses of separated RCTs failed to find
      significant differences in favor of one or another choice. However, results from
      most observational studies, including well designed prospective pragmatic
      randomised analyses, demonstrated the superiority of swapping over cycling
      approach, whereas only few studies reported a comparable effectiveness. In this
      review, we aimed to critically analyze all the potential therapeutic options for
      the treatment of first-line bDMARD failures in order to provide a comprehensive
      overview of available strategies to be applied in clinical practice.

PMID- 29037900
TI  - Autoimmune comorbidity in chronic spontaneous urticaria: A systematic review.
AB  - BACKGROUND AND OBJECTIVE: Numerous autoimmune diseases (AIDs) have been linked to
      chronic spontaneous urticaria (CSU). Here, we provide the first extensive and
      comprehensive evaluation of the prevalence of AIDs in patients with CSU and vice
      versa. METHODS: A Pubmed and Google Scholar search was performed to identify
      studies reporting the prevalence of various AIDs in CSU and vice versa published
      before April 2017. RESULTS: The prevalence of individual AIDs in CSU is increased
      (>=1% in most studies vs <=1% in the general population). AIDs with relatively
      high prevalence in the general population are also quite common in CSU patients,
      whereas those with low prevalence remain a rare finding in CSU. The rates of
      comorbidity in most studies were >=1% for insulin-dependent diabetes mellitus,
      rheumatoid arthritis (RA), psoriasis and celiac disease (CD), >=2% for Graves'
      disease, >=3% for vitiligo, and >=5% for pernicious anemia and Hashimoto's
      thyroiditis. Organ-specific AIDs are more prevalent in CSU than systemic
      (multiorgan or non organ-specific) AIDs. >2% of CSU patients have autoimmune
      polyglandular syndromes encompassing autoimmune thyroid disease (ATD) and
      vitiligo or pernicious anemia. Antithyroid and antinuclear antibodies are the
      most prevalent AID-associated autoantibodies in CSU. >15% of CSU patients have a
      positive family history for AIDs. The prevalence of urticarial rash in AID
      patients is >1% in most studies. This rash is more prevalent in eosinophilic
      granulomatosis with polyangiitis, ATD, systemic lupus erythematosus, RA and CD.
      CONCLUSIONS: CSU patients have an increased risk of AIDs, especially adult female
      patients and those with a positive family history and a genetic predisposition
      for AIDs, who should be screened for signs and symptoms of AIDs.

PMID- 29037901
TI  - HLA-DRB1 alleles and juvenile idiopathic arthritis: Diagnostic clues emerging
      from a meta-analysis.
AB  - Juvenile Idiopathic Arthritis (JIA) is characterized with a variable pattern of
      articular involvement and systemic symptoms and, thus, it has been classified in
      several subtypes. Genetic predisposition to JIA is mainly due to HLA class II
      molecules (HLA-DRB1, HLA-DPB1), although HLA class I molecules and non-HLA genes
      have been implicated, too. Here, we carried out a meta-analysis including
      selected studies designed to assess HLA genetic background of JIA patients,
      compared to healthy controls; particularly, we focused our attention on HLA-DRB1.
      In summary, our meta-analysis showed four main findings regarding HLA-DRB1 locus
      as a genetic factor of JIA: i) HLA-DRB1*08 is a strong factor predisposing to
      JIA, both for oligo-articular and poly-articular forms (oJIA>pJIA); ii) HLA
      DRB1*01 and HLA-DRB1*04 may be involved in the genetic predisposition of
      Rheumatoid Factor (RF) positive forms of JIA; iii) HLA-DRB1*11 was confirmed to
      be predisposing to oligo-articular JIA; iv) HLA-DRB1*04 was confirmed to have a
      role in systemic JIA. Importantly, RF positivity seems to select the JIA clinical
      subset with the strongest immunogenetic similarities with adult rheumatoid
      arthritis.

PMID- 29037902
TI  - Cogan syndrome: Characteristics, outcome and treatment in a French nationwide
      retrospective study and literature review.
AB  - BACKGROUND: Cogan syndrome is mainly treated with steroids. We aimed to determine
      the place of DMARDs and biologic-targeted treatments. PATIENTS AND METHODS: We
      conducted a French nationwide retrospective study of patients with Cogan syndrome
      (n=40) and a literature review of cases (n=22) and analyzed the efficacy of
      disease-modifying anti-rheumatic drugs (DMARDs) and tumor necrosis factor alpha
      (TNF-alpha) antagonists. RESULTS: We included 62 patients (31 females) (median
      age 37years [range 2-76]. At diagnosis, 61 patients (98%) had vestibulo-auditory
      symptoms, particularly bilateral hearing loss in 41% and deafness in 31%. Ocular
      signs were present in 57 patients (92%), with interstitial keratitis in 31 (51%).
      The first-line treatment consisted of steroids alone (n=43; 70%) or associated
      with other immunosuppressive drugs (n=18; 30%). Overall, 13/43 (30%) and 4/18
      (22%) patients with steroids alone and with associated immunosuppressive drugs,
      respectively (p=0.8), showed vestibulo-auditory response; 32/39 (82%) and 15/19
      (79%) ocular response; and 23/28 (82%) and 10/14 (71%) general response. Overall
      61 patients had used a total of 126 lines of treatment, consisting of steroids
      alone (n=51 lines), steroids with DMARDs (n=65) and infliximab (n=10). Vestibulo
      auditory response was significantly more frequent with infliximab than DMARDs or
      steroids alone (80% vs 39% and 35%, respectively), whereas ocular, systemic and
      acute-phase reactant response rates were similar. Infliximab was the only
      significant predictor of vestibulo-auditory improvement (odds ratio 20.7 [95%
      confidence interval 1.65; 260], p=0.019). CONCLUSION: Infliximab could lead to
      vestibulo-auditory response in DMARDS and steroid-refractory Cogan syndrome, but
      prospective studies are necessary.

PMID- 29037903
TI  - Novelties in the field of autoimmunity - 1st Saint Petersburg congress of
      autoimmunity, the bridge between east and west.

PMID- 29037904
TI  - Rheumatic diseases and autoimmune vascular dementia.
AB  - Vascular dementia (VD) comes second after Alzheimer's disease (AD) as a cause of
      impaired cognition. VD is not a specific nosological entity, but rather a
      syndrome encompassing a number of diseases caused by impaired supply of blood to
      the brain. Systemic autoimmune disorders such as systemic lupus erythematosus,
      rheumatoid arthritis, vasculitis and antiphospholipid syndrome (APS) can be
      associated with dementia. VD is often related to the presence of traditional
      cardiovascular risk factors, but it may also be associated with a host of
      disorders affecting the brain blood vessels, neuronal cells, or both. It is
      important to entertain in the differential diagnosis of VD, to recognize and to
      cure them accurately in order to preserve life's quality of our patients.

PMID- 29037905
TI  - The inter-observer reading variability in anti-nuclear antibodies indirect (ANA)
      immunofluorescence test: A multicenter evaluation and a review of the literature.
AB  - Recently there has been an increase demand for Computer-Aided Diagnosis (CAD)
      tools to support clinicians in the field of Indirect ImmunoFluorescence (IIF), as
      the novel digital imaging reading approach can help to overcome the reader
      subjectivity. Nevertheless, a large multicenter evaluation of the inter-observer
      reading variability in this field is still missing. This work fills this gap as
      we evaluated 556 consecutive samples, for a total of 1679 images, collected in
      three laboratories with IIF expertise using HEp-2 cell substrate (MBL) at 1:80
      screening dilution according to conventional procedures. In each laboratory, the
      images were blindly classified by two experts into three intensity classes:
      positive, negative, and weak positive. Positive and weak positive ANA-IIF results
      were categorized by the predominant fluorescence pattern among six main classes.
      Data were pairwise analyzed and the inter-observer reading variability was
      measured by Cohen's kappa test, revealing a pairwise agreement little further
      away than substantial both for fluorescence intensity and for staining pattern
      recognition (k=0.602 and k=0.627, respectively). We also noticed that the inter
      observer reading variability decreases when it is measured with respect to a gold
      standard classification computed on the basis of labels assigned by the three
      laboratories. These data show that laboratory agreement improves using digital
      images and comparing each single human evaluation to potential reference data,
      suggesting that a solid gold standard is essential to properly make use of CAD
      systems in routine work lab.

PMID- 29037906
TI  - Uveitis: Diagnostic work-up. A literature review and recommendations from an
      expert committee.
AB  - PURPOSE: Diagnosis of uveitis is difficult. Etiologic investigations should take
      into account the epidemiology of uveitis and should focus on the most severe
      forms of the disease and those which can be treated. This study was undertaken to
      establish recommendations for the diagnosis of uveitis. METHODS: Recommendations
      were developed by a multidisciplinary panel of 14 experts, including internists,
      ophthalmologists, and rheumatologists, and are based on a review of the
      literature and the results of the ULISSE study, which was the first prospective
      study to assess the efficacy of a standardized strategy for the etiologic
      diagnosis of uveitis. The following groups of patients are not included in these
      recommendations: children, immunocompromised patients, patients with severe
      retinal vasculitis, and those with specific eye diseases diagnosed by
      ophthalmologic examination only. RESULTS: Diagnosis should be guided by the
      medical history of the patient and physical examination. Serologic screening for
      syphilis is appropriate in all forms of uveitis. If uveitis is not diagnosed at
      this stage, investigations oriented by the anatomic characteristics of uveitis
      are proposed. These consist of assays for HLA-B27 (in unilateral acute anterior
      non-granulomatous uveitis), serum angiotensin-converting enzyme, interferon-gamma
      release, chest computed tomography (chronic uveitis), cerebral magnetic resonance
      imaging and anterior chamber tap with interleukin-10 analysis (intermediate or
      posterior uveitis in patients >40years-old). Other investigations prescribed in
      the absence of orientation are usually unhelpful. CONCLUSIONS: A strategy is
      proposed for the etiologic diagnosis of uveitis. The benefit of more invasive
      investigations remains to be determined.

PMID- 29037907
TI  - Interleukin-22 in human inflammatory diseases and viral infections.
AB  - Interleukin-22 (IL22) is one of the members of IL10 family. Elevated levels of
      this cytokine can be seen in diseases caused by T lymphocytes, such as Psoriasis,
      Rheumatoid arthritis, interstitial lung diseases. IL22 is produced by different
      cells in both innate and acquired immunities. Different types of T cells are able
      to produce IL22, but the major IL22-producing T-cell is the TCD4. TH22 cell is a
      new line of TCD4 cells, which differentiated from naive T cells in the presence
      of TNFalpha and IL6; 50% of peripheral blood IL22 is produced by these cells.
      IL22 has important functions in host defense at mucosal surfaces as well as in
      tissue repair. In this review, we assess the current understanding of this
      cytokine and focus on the possible roles of IL-22 in autoimmune diseases.

PMID- 29037908
TI  - New insights in the pathogenesis of immunoglobulin A vasculitis (Henoch-Schonlein
      purpura).
AB  - Immunoglobulin A vasculitis (IgAV), also referred to as Henoch-Schonlein purpura,
      is the most common form of childhood vasculitis. The pathogenesis of IgAV is
      still largely unknown. The disease is characterized by IgA1-immune deposits,
      complement factors and neutrophil infiltration, which is accompanied with
      vascular inflammation. Incidence of IgAV is twice as high during fall and winter,
      suggesting an environmental trigger associated to climate. Symptoms can resolve
      without intervention, but some patients develop glomerulonephritis with features
      similar to IgA nephropathy that include hematuria, proteinuria and IgA deposition
      in the glomerulus. Ultimately, this can lead to end-stage renal disease. In IgA
      nephropathy immune complexes containing galactose-deficient (Gd-)IgA1 are found
      and thought to play a role in pathogenesis. Although Gd-IgA1 complexes are also
      present in patients with IgAV with nephritis, their role in IgAV is disputed.
      Alternatively, it has been proposed that in IgAV IgA1 antibodies are generated
      against endothelial cells. We anticipate that such IgA complexes can activate
      neutrophils via the IgA Fc receptor FcalphaRI (CD89), thereby inducing neutrophil
      migration and activation, which ultimately causes tissue damage in IgAV. In this
      Review, we discuss the putative role of IgA, IgA receptors, neutrophils and other
      factors such as infections, genetics and the complement system in the
      pathogenesis of IgA vasculitis.

PMID- 29037909
TI  - Treatment of oral refractory large area mucosal leukoplakia with CO2 laser
      combined with photodynamic therapy: Case report.

PMID- 29037910
TI  - Antimicrobial photodynamic therapy for infectious stomatitis in snakes: Clinical
      views and microbiological findings.
AB  - BACKGROUND: Antimicrobial photodynamic therapy (APDT) has been broadly
      investigated as an alternative to treat localized infections, without leading to
      the selection of resistant microorganisms. Infectious stomatitis is a
      multifactorial disease frequently reported in captive snakes characterized by
      infection of the oral mucosa and surrounding tissues. In this study, we
      investigated methylene blue (MB)-mediated APDT to treat infectious stomatitis in
      snakes and verified the resistance phenotype and genotype before and after APDT.
      METHODS: Three Boid snakes presented petechiae, edema and caseous material in
      their oral cavities. MB (0.01%) was applied on the lesions and after 5min they
      were irradiated using a red laser (lambda=660nm), fluence of 280J/cm2, 8J and 80s
      per point, 100mW, spot size 0.028cm2 and fluence rate of 3.5W/cm2. APDT was
      repeated once a week during 3 months. Samples of the lesions were collected to
      identify bacteria and antibiotic resistance profiles. To analyze the clonality of
      bacterial isolates before and after APDT, isolates were subjected to ERIC PCR
      analysis. RESULTS: Snakes presented clinical improvement such as reduction of
      inflammatory signs and caseous material. Pseudomonas aeruginosa and Escherichia
      coli were present in all snakes; Klebsiella pneumoniae and Morganella morganii
      were also identified in some animals. We also observed that the oral microbiota
      was completely replaced following APDT. However, K. pneumoniae isolates before
      and after APDT were a single clone with 100% of genetic similarity that lost
      resistance phenotype for seven antibiotics of four classes. CONCLUSIONS: These
      results show that APDT can be used to treat infectious stomatitis in snakes.

PMID- 29037911
TI  - Assessing daylight & low-dose rate photodynamic therapy efficacy, using
      biomarkers of photophysical, biochemical and biological damage metrics in situ.
AB  - BACKGROUND: Sunlight can activate photodynamic therapy (PDT), and this is a
      proven strategy to reduce pain caused byconventional PDT treatment, but
      assessment of this and other alternative low dose rate light sources, and their
      efficacy, has not been studied in an objective, controlled pre-clinical setting.
      This study used three objective assays to assess the efficacy of different PDT
      treatment regimens, using PpIX fluorescence as a photophysical measure, STAT3
      cross-linking as a photochemical measure, and keratinocyte damage as a
      photobiological measure. METHODS: Nude mouse skin was used along with in vivo
      measures of photosensitizer fluorescence, keratinocyte nucleus damage from
      pathology, and STAT3 cross-linking from Western blot analysis. Light sources
      compared included a low fluence rate red LED panel, compact fluorescent bulbs,
      halogen bulbs and direct sunlight, as compared to traditional PDT delivery with
      conventional and fractionated high fluence rate red LED light delivery. RESULTS:
      Of the three biomarkers, two had strong correlation to the PpIX-weighted light
      dose, which is calculated as the product of the treatment light dose (J/cm2) and
      the normalized PpIX absorption spectra. Comparison of STAT3 cross-linking to PpIX
      weighted light dose had an R=0.74, and comparison of keratinocyte nuclear damage
      R=0.70. There was little correlation to PpIX fluorescence. These assays indicate
      most of the low fluence rate treatment modalities were as effective as
      conventional PDT, while fractionated PDT showed the most damage. CONCLUSIONS:
      Daylight or artificial light PDT provides an alternative schedule for delivery of
      drug-light treatment, and this pre-clinical assay demonstrated that in vivo
      assays of damage could be used to objectively predict a clinical outcome in this
      altered delivery process.

PMID- 29037912
TI  - Early emergence of altered 5-HT2A receptor-evoked behavior, neural activation and
      gene expression following maternal separation.
AB  - The early stress of Maternal Separation (MS) contributes to the establishment of
      adult psychopathology. The serotonergic (5-HT) system is implicated during this
      temporal window in mediating the development of mood-related behaviors. MS is
      reported to evoke altered 5-HT2A receptor function in adulthood. However, the
      ontogeny of altered 5-HT2A receptor responsivity following MS remains unknown.
      Here, we examined 5-HT2A receptor agonist, DOI (1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane) (2mg/kg) evoked responses, namely stereotypical head-twitch
      behaviors in control and MS Sprague-Dawley rat pups at postnatal day 21 (P21). MS
      involved a separation of pups from the dam for 3h daily from postnatal day 2-14.
      MS pups at P21 exhibited significantly enhanced head-twitch behaviors compared to
      controls. Using c-Fos cell counting we examined neural activation in control and
      MS pups following DOI treatment. MS pups exhibited altered DOI-evoked c-Fos
      expression within all mPFC subdivisions, but not in the hippocampus, lateral
      septum and hypothalamus, suggesting differential prefrontal neural activation
      upon 5-HT2A receptor stimulation following early stress. Gene profiling of 5-HT2A
      receptor-regulated immediate early genes (IEGs) indicated a decline in the
      expression of Fos, Fra1 and Egr1 mRNA under baseline conditions in the mPFC of MS
      pups. MS pups also showed an altered pattern in the regulation of several 5-HT2A
      receptor-regulated IEGs (Fos, Fra1, Bdnf, Egr1, Egr3) following DOI treatment.
      Collectively, these results highlight an early emergence of altered 5-HT2A
      receptor-evoked behavioral responses and neural activation patterns in multiple
      brain regions in animals with a history of MS.

PMID- 29037913
TI  - Gestational age modulates neural correlates of intentional, but not automatic
      number magnitude processing in children born preterm.
AB  - Premature birth is a significant risk factor for learning disabilities in general
      and mathematics learning difficulties in particular. However, the exact reasons
      for this relation are still unknown. While typical numerical development is
      associated with a frontal-to-parietal shift of brain activation with increasing
      age, influences of gestational age have hardly been considered so far. Therefore,
      we investigated the influence of gestational age on the neural correlates of
      number processing in 6- and 7-year-old children born prematurely (n=16). Only the
      numerical distance effect - as a measure of intentional number magnitude
      processing - elicited the fronto-parietal activation pattern typically observed
      for numerical cognition. On the other hand, the size congruity effect - as a
      measure of automatic number magnitude processing - was associated with activation
      of brain areas typically attributed to cognitive control. Most importantly,
      however, we observed that gestational age reliably predicted the frontal-to
      parietal shift of activation observed for the numerical distance effect. Our
      findings seem to indicate that human numerical development may start even before
      birth and prematurity might hamper neural facilitation of the brain circuitry
      subserving numerical cognition. In turn, this might contribute to the high risk
      of premature children to develop mathematical learning difficulties.

PMID- 29037914
TI  - Antimicrobial activity and preliminary mode of action of PlnEF expressed in
      Escherichia coli against Staphylococci.
AB  - Strains belonging to the genus of Staphylococci, such as Staphylococcus aureus
      are common pathologic bacteria which may cause nosocomial cross infection and
      food contamination. Plantaricin EF (PlnEF), a two-peptide nonlantibiotic
      bacteriocin produced by Lactobacillus plantarum strains, shows great inhibitory
      effects against Gram-positive Staphylococci strains. To overproduce this two
      peptide bacteriocin, plnE and plnF genes were cloned into pET32a (+) vector and
      heterologously expressed in Escherichia coli by fusion with His6-tag in this
      study. The purified fusion proteins were cleaved by enterokinase, then PlnE and
      PlnF peptides without extra amino acids were obtained by a two-step purification
      method, ultrafiltration centrifuge (10 kDa) followed by a reverse-phase HPLC.
      Purity of PlnE and PlnF, determined by analytical HPLC, is ~98%, and their
      molecular mass confirmed by ESI-MS was 3545.14 Da and 3703.1 Da, respectively. It
      was found that the two peptides had significant antimicrobial activities against
      Staphylococcus citreus and Staphylococcus aureus strains and they functioned
      synergistically. PlnEF exerted its bactericidal activity against Staphylococci
      strains by permeabilizing the cell membrane, causing influx and efflux of various
      molecules across the transmembrane barrier, eventually leading to cell death.

PMID- 29037915
TI  - Linalool-rich essential oils from the Amazon display antidepressant-type effect
      in rodents.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The essential oils of the leaves of Aniba
      rosaeodora (pau-rosa), Aniba parviflora (macacaporanga) and Aeollanthus
      suaveolens (catinga-de-mulata), rich in linalool, are used in the traditional
      medicine of the Brazilian Amazon for its effects on the central nervous system,
      such as sedative, anticonvulsant and antidepressant, among other therapeutic
      properties. AIM OF THE STUDY: To analyze the chemical composition of these oils
      and to evaluate their neurobehavioral effects in rodents, based on different and
      established behavioral tests. MATERIAL AND METHODS: The oils were distilled and
      analyzed by GC and GC-MS. Male Wistar rats received intraperitoneal doses of the
      oils of pau-rosa (3.5 and 35mg/kg), macacaporanga (8.5 and 85mg/kg) and catinga
      de-mulata (7.5 and 75mg/kg), in addition to a linalool standard (30mg/kg). The
      neurobehavioral effects were evaluated using the tests: Open Field (spontaneous
      locomotion activity), Elevated Plus Maze (anxiolytic- type activity), Splash and
      Forced Swimming (antidepressive-type activity) and the Inhibitory Avoidance
      (memory retention). RESULTS: The three oils (highest dose) and standard linalool
      presented significant antidepressant activity in rodents. Linalool was identified
      as the major constituent of the oils (pau-rosa, 88.6%, macacaporanga, 45%,
      catinga-de-mulata, 49.3%). The standard linalool used was 97.0%. CONCLUSION: The
      pau-rosa, macacaporanga, and catinga-de-mulata oils presented antidepressant
      activity due to the presence of linalool, which, by the final synergistic action
      of other constituents found in oils, may have contributed to the increase or
      reduction of this behavioral effect in the treated animals. A relevant fact is
      that there was no compromise of spontaneous locomotion and the memory retention
      in the rodents.

PMID- 29037916
TI  - Pfaffia paniculata (Brazilian ginseng) extract modulates Mapk and mucin pathways
      in intestinal inflammation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pfaffia paniculata is an endemic Brazilian plant
      traditionally used against fatigue, stress, inflammation and low immune system as
      well as with proven intestinal anti-inflammatory activity. AIM OF THE STUDY: To
      evaluate intestinal anti-inflammatory effects of P. paniculata on the mRNA
      abundance of Hsp70, Heparanase, Mapk1, Mapk3, Mapk6, Mapk9, Muc1, Muc2, Muc3,
      Muc4, and NF-kappaB, as well as the mucin content in colonic samples. MATERIAL
      AND METHODS: Intestinal inflammation was induced by TNBS and rats were divided
      into groups that received vehicle or 25, 50, 100, or 200mg/kg of P. paniculata
      extract, p.o., started 2h after inflammation induction and continued daily for 7
      days. At the end of the procedure, the animals were killed and their colon
      samples were obtained for RT-qPCR analysis and mucin histochemical study with
      PAS/Alcian blue stain. The inflammatory process was confirmed with colon
      macroscopic analysis and myeloperoxidase (MPO) activity. RESULTS: P. paniculata
      at 200mg/kg significantly decreased macroscopic damage score, extension of lesion
      and colonic MPO activity. Besides, P. paniculata at a dose of 25mg/kg was also
      able to significantly decrease Hsp70, while treatment with 50mg/kg reduced Mapk3
      and increased Muc4. At dose of 100mg/kg P. paniculata increased Mapk1, Muc3,
      Muc4, and decreased Mapk3. Finally, at the 200mg/kg P. paniculata reduced Mapk3.
      The heparanase, NF-kappaB, Mapk6, Mapk9, Muc1 and Muc2 mRNA abundances were not
      altered after P. paniculata treatments. CONCLUSION: Intestinal anti-inflammatory
      activity of P. paniculata was related to modulation of Mapks and mucin gene
      expression, as well as mucus secretion in intestinal inflammation.

PMID- 29037917
TI  - Immunomodulation after radiofrequency ablation of locally advanced pancreatic
      cancer by monitoring the immune response in 10 patients.
AB  - OBJECTIVE/BACKGROUND: RFA of pancreatic cancer has been demonstrated to be
      feasible and safe with a positive impact on survival. The aim was to investigate
      whether an immune reaction is activated after locally advanced pancreatic cancer
      (LAPC) ablation. METHODS: Peripheral Blood samples were obtained preoperatively
      and on post-operative days 3-30. Evaluated parameters were: cells [CD4+, CD8+ and
      activated subsets, T-Reg, Monocytes, myeloid and plasmocytoid Dendritic cells
      (mDC and pDC)] and cytokines [Interleukin (IL)-6, Stromal-cells derived factor
      (SDF)-1, IL-1beta, Tumour-Necrosis Factor (TNF)-alpha, Interferon (IFN)-gamma,
      Vascular Endothelial Growth Factor (VEGF), chemokine (C-C motif) ligand 5 (CCL
      5), Transforming-Growth Factor (TGF)-beta]. RESULTS: Ten patients were enrolled.
      CD4+, CD8+ and TEM increased from day 3 suggesting the activation of the adaptive
      response. Immunosuppressive T-Reg cells were stable despite the possibility that
      laparotomy and heating might favour their expansion. Myeloid DCs, that present
      tumour-associated antigens, increased at day 30. RFA dramatically increased
      circulating IL-6 at day 3 but this decreased to baseline by day 30, consistent
      with the supposed anti-tumour effect. RFA did not significantly modulate
      essential chemokines, such as CCL-5 and SDF1, VEGF, TGF-beta and TNF-alpha, that
      favour tumour-growth by sustaining cancer angiogenesis and fuelling tumour
      associated inflammation. CONCLUSIONS: This study provides the first evidence of
      RFA-based immunomodulation in LAPC. We observed a general activation of adaptive
      response along with a decrease of immunosuppression. Furthermore, most cells
      showed prolonged activation some weeks after the procedure, suggesting true
      immunomodulation rather than a normal inflammatory response.

PMID- 29037918
TI  - Monitoring of incremental changes in maximum interincisal opening after gap
      arthroplasty omits the risk of Re-ankylosis.
AB  - PURPOSE: The aim of this clinical study was to prospectively measure the
      incremental changes in the maximum interincisal opening (MIO) after 1 cm gap
      arthroplasty, compare these changes between unilateral and bilateral cases, and
      emphasize the importance of the monitoring of the MIO for at least 24 months.
      MATERIALS AND METHODS: This prospective study enrolled 26 patients with TMJ
      ankylosis either unilateral or bilateral. The fingers assessment method was used
      to measure the MIO preoperatively, intraoperatively, and monthly postoperatively
      up to 24 months. All the patients had undergone 1 cm gap arthroplasty to release
      the ankylosis. The changes in MIO measurements of unilateral and bilateral cases
      were statistically compared. The physiotherapy was performed until the
      measurements had normal stable values. RESULTS: All the cases showed a
      significant decrease in MIO at the first three months. At 6 months, the MIO
      continuously increased up to 1 year. There was no difference between the
      unilateral and bilateral cases. At the end of the follow-up, all measurements
      showed normal stable values. CONCLUSION: The monitoring of MIO is important to
      detect the early signs of re-ankylosis. It is the only way that can be used in
      which the early signs cannot be detected in radiographs.

PMID- 29037919
TI  - Biomechanical comparison of a multidirectional locking plate and conventional
      plates for the osteosynthesis of mandibular angle fractures-A preliminary study.
AB  - PURPOSE: The objective of surgical fracture management is to reduce and fixate
      fractures accurately and rapidly. Two osteosynthesis plates are usually used in
      the treatment of mandibular angle fractures to enhance torsional stiffness. We
      conducted biomechanical tests under static and cyclic loading to assess whether a
      single locking plate is as efficacious as two conventional plates in the
      osteosynthesis of mandibular angle fractures. MATERIALS AND METHODS: Fracture
      gaps were created in synthetic mandible replicas. After pretests, the stiffness
      of a single locking plate and different types of non-locking, two-plate systems
      was assessed and compared under static and cyclic loading. The plates were
      subjected to a maximum static load of 750 N and underwent cyclic loading at a
      constant force of 400 N during a maximum of 500,000 cycles. RESULTS: No plastic
      deformation occurred in the static tests. Both types of osteosynthesis showed
      high static stability. The locking plate was significantly stiffer than the non
      locking plates (p = 0.0079). Cyclic loading tests did not reveal any significant
      differences. CONCLUSION: Within the limitations of this preliminary study, a
      single locking miniplate appears to be as efficacious in biomechanical tests as
      non-locking, two-plate systems for the management of mandibular angle fractures.

PMID- 29037920
TI  - Tongue movement during articulation in magnetic resonance imaging: Findings in 20
      healthy volunteers and a patient with anterior floor of the mouth squamous cell
      carcinoma.
AB  - PURPOSE: Combined ablative and reconstructive oral maxillofacial surgery involves
      a multitude of anatomical and functional structures for speech and swallowing.
      Although there are a few methods to objectively examine swallowing function, this
      is not true for speech. We describe the development of an objective visualization
      and measurement tool for magnetic resonance imaging (MRI) to evaluate speech and
      its first application in a patient. MATERIAL AND METHODS: A total of 20 healthy
      patients and one patient with squamous cell carcinoma localized in the anterior
      floor of the mouth were included in the study. Examination included an MRI
      examination of a paced, defined set of fictive words representing all sounds of
      the German language. The patient underwent MRI preoperatively and 1, 3, 6 and 12
      months postoperatively. MRI findings were correlated with speech intelligibility.
      RESULTS: In sagittal planes, the correct identification of vowels and consonants
      was feasible and showed a high accordance between two independent observers and
      repetitions. Measurements for the patient showed significant deviations 1 month
      postoperatively but gradually decreased over time. Aberrant values were
      persistent for sound /s/. Findings correlated with clinical findings of speech
      intelligibility. CONCLUSION: The presented tool seems to be promising for
      evaluating articulation in (tumor) patients.

PMID- 29037921
TI  - TLR expression profile of human alveolar bone proper-derived stem/progenitor
      cells and osteoblasts.
AB  - Alveolar bone proper-derived mesenchymal stem/progenitor cells (AB-MSCs) and
      alveolar osteoblasts (OBs) are pivotal cells with positive attributes in
      regenerative medicine. During regenerative approaches, AB-MSCs may interact with
      their surrounding environment via their expressed toll-like-receptors (TLRs).
      This study aimed to depict for the first time the TLRs expression profile of AB
      MSCs and OBs. Cells were isolated from human alveolar bone proper, and STRO-1
      immunomagnetically sorted to segregate AB-MSCs and OBs. Cell populations were
      separately seeded out to obtain single colony forming units (CFUs), and were
      characterized for CD14, CD34, CD45, CD73, CD90, CD105, and CD146 expression as
      well as for their multilineage differentiation potential. Following incubation of
      AB-MSCs and OBs in basic medium, their TLRs expression profiles were
      characterized at mRNA and protein levels. In contrast to OBs, AB-MSCs showed all
      predefined mesenchymal stem/progenitor cell characteristics. At a protein level,
      AB-MSCs showed a distinctive expression profile of TLRs 1, 2, 3, 4, 5, 6, 7, 8,
      and 10 in different quantities, without TLR9 expression. According to their
      median expression values, TLR2 was the highest expressed, followed by TLRs 4, 5,
      7, 1, 10, 8, 3, and finally 6. In contrast, OBs did not express TLR3 and TLR9.
      According to their median expression values they further showed a different
      sequence of TLRs expression, with TLR2 highest expressed, followed by TLRs 10, 4,
      7, 5, 1, 8, and 6. This study describes for the first time the characteristic
      TLRs expression profile of AB-MSCs as well as OBs, which could impact their
      specific sensitivity to pathogenic as well as body tissue compounds, and their
      therapeutic potential in-vivo.

PMID- 29037922
TI  - Oral vitamin B1-substitution does not decrease genetically determined cleft rate
      in mice (A/WySn).
AB  - PURPOSE: Cleft lip and palate (CL/P) are one of the most common human birth
      defects. Animal experiments and clinical investigations show a clear reduction of
      teratogenic clefts by a high-dose vitamin B supplementation during early
      pregnancy, especially in families at risk (reduction of recurrence). The aim of
      this work was to examine the influence of thiamine (vitamin B1) on CL/P
      appearance in genetically determined A/WySn mice within different supplementation
      starting points. MATERIALS AND METHODS: A total of 24 A/WySn female mice were
      orally supplemented with high doses (80 mg/kg) of thiamine at different times of
      pregnancy (5 groups, n = 90). The influence of thiamine on the abortion rate and
      CL/P appearance in the offspring was analyzed with respect to the concentration
      of thiamine in the serum and amniotic fluid (HPLC-chromatography). Immunochemical
      analyses of the ThTr-1 und ThTr-2 receptor-status were performed in midface
      sections of A/WySn-fetuses and the corresponding placenta, with and without CL/P.
      RESULTS: High doses of orally supplemented thiamine did not reduce the CL/P
      appearance in A/WySn mice. However, the different starting points of vitamin B1
      substitution had some influence. Additionally, an obvious decrease in aborted
      fetuses was noticed in all supplemented groups. The oral substitution caused a
      clear increase of the serum concentration in all mothers, but showed no increase
      of the amniotic fluid concentration. Then immunohistochemistry detected an
      overexpression of ThTr-1 in the midface and an irregular localization of ThTr-2
      in the placenta of fetuses with clefts. CONCLUSION: Our results suggest a time
      dependent influence of thiamine on CL/P appearance in female mice. The
      prophylactic/periconceptional, but not the therapeutic supplementation, starting
      point can be proposed as a crucial step for regular facial and palatal fusion in
      embryonic development. The absolute rate of CL/P was not reduced, and the
      concentration of the water-soluble thiamine could not increase in the amniotic
      fluid. Thus the proposed local effect of thiamine failed in the development of
      genetically determined mice.

PMID- 29037923
TI  - WITHDRAWN: Toxicity of triptolide and the molecular mechanisms involved.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
      business/policies/article-withdrawal.

PMID- 29037924
TI  - "All-Inside" Arthroscopic Treatment of Tillaux-Chaput Fractures: Clinical
      Experience and Outcomes Analysis.
AB  - We investigated all-inside ankle arthroscopy for Tillaux-Chaput fractures. We
      retrospectively evaluated 19 patients (12 males [63.2%] and 7 [36.8%] females; 11
      right [57.9%] and 8 left [42.1%] ankles) treated from May 2013 to January 2016.
      Their mean age was 28.1 (range 10 to 55) years. Sixteen (84.2%) had single
      Tillaux-Chaput fractures and 3 (15.8%) had combined proximal fibular fractures;
      17 (89.5%) were diagnosed radiographically and 2 (10.5%) by computed tomography.
      Anterolateral and anteromedial ankle arthroscopy was used for closed reduction
      and internal fixation with 1 or 2 Herbert screws. Joint function was evaluated
      using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot
      scale. All 19 patients healed by first intention without nerve, vessel, or tendon
      injuries. The follow-up was 19.0 (range 12 to 25) months; fracture union was
      achieved by 23.5 (range 12 to 36) weeks. At the last follow-up, the 19 patients
      had no restrictions in ankle function and range of motion, with no ankle or
      walking pain. The AOFAS score changed from 52.8 to 91.7 points, with an
      excellent/good rate of 100%. These results suggest that anterolateral and
      anteromedial all-inside ankle arthroscopy is a precise and effective method for
      closed reduction and internal fixation of Tillaux-Chaput fractures.

PMID- 29037925
TI  - Radiographic Union Scoring Scale for Determining Consolidation Rates in the
      Calcaneus.
AB  - The reliable evaluation of osseous consolidation after hindfoot osteotomy can be
      difficult. Concomitant hindfoot osteotomies often dictate the advancement of
      weightbearing, and radiographs are the mainstay imaging tool owing to cost,
      efficiency, and radiation exposure. Understanding the radiographic parameters
      that can be used to reliably determine osseous healing is paramount. However,
      currently, no reliable or validated method is available to determine osseous
      healing of hindfoot osteotomies in irregular bones of the foot. The purpose of
      the present study was to develop a radiographic healing scoring system that would
      enhance the diagnostic healing assessment after elective calcaneal osteotomy. We
      adapted existing orthopedic scales validated for healing in the leg for
      application in the irregular bones of the foot. A total of 168 cases were
      evaluated by 6 blinded assessors to test the interrater reliability of subjective
      healing assessment compared with the proposed scoring system. The radiographs
      were classified by postoperative period: <=4 weeks, 5 to 12 weeks, and >12 weeks.
      The proposed scale had high interrater reliability but was burdensome. Using a
      priori item reduction protocols, a limited 6-item scale further improved internal
      consistency and reduced the burden. The result was excellent interrater
      reliability (alpha = 0.98, standard deviation 0.02, 95% confidence interval 0.91
      to 0.96) among all assessors when using the scoring scale compared with
      unacceptable reliability (alpha = 0.438) for subjective osteotomy healing. The
      reliability of our system appeared superior to that of subjective assessment of
      osseous healing alone, even in the absence of clinical correlates after osteotomy
      of the calcaneus.

PMID- 29037926
TI  - Comparison of Clamp Reduction and Manual Reduction of Syndesmosis in Rotational
      Ankle Fractures: A Prospective Randomized Trial.
AB  - An optimal outcome of surgical treatment for a syndesmotic injury depends on
      accurate reduction and adequate fixation. It has been suggested that the use of a
      reduction clamp for reduction of the syndesmosis results in better reduction and
      a lower rate of redisplacement than manual reduction. However, these concepts
      have never been scientifically evaluated. We compared these 2 methods in a
      prospective randomized trial. A total of 85 acute ankle rotational fractures
      combined with syndesmotic injury were randomized to syndesmosis reduction with
      either a reduction clamp or manual manipulation. Reduction of the syndesmosis was
      assessed radiographically by measuring the tibiofibular clear space, tibiofibular
      overlap, and the medial clear space immediately postoperatively and at the final
      follow-up examination. Ankle joint range of motion, visual analog scale score,
      Olerud-Molander ankle scoring system, and complications were obtained at the last
      follow-up visit to assess the clinical outcomes. Of the 3 radiographic
      measurements, the tibiofibular clear space and tibiofibular overlap differed
      significantly between the 2 groups (p < .05). The clinical outcomes did not
      differ significantly between the 2 groups (p > .05). Although differences were
      found in the radiographic measurements, most syndesmoses in both groups were
      within the normal range at the final follow-up visit, and the 2 methods of
      syndesmosis reduction provided similar clinical outcomes. Accordingly, the
      results of the present study suggest that both of these methods are effective and
      reliable for reduction of the syndesmosis in rotational ankle fractures.

PMID- 29037927
TI  - Short-Term Outcomes of Open Reduction and Internal Fixation for Sanders Type III
      Calcaneal Fractures With and Without Bone Grafts.
AB  - Calcaneal fractures, often caused by a fall from a height, are the most common
      injuries encountered by orthopedic surgeons. Currently, open anatomic reduction
      and internal fixation (ORIF) is considered a valuable treatment of displaced
      intraarticular fractures of the calcaneus; however, the need for bone grafting in
      the treatment is still controversial. Therefore, in the present study, we
      investigated the outcomes of 2 methods (with and without bone grafting) used for
      the surgical treatment of Sanders type III calcaneal fractures. From January 2013
      to September 2015, 57 cases (55 patients) with displaced Sanders type III
      calcaneal fractures (53 unilateral and 2 bilateral) were enrolled. The patients
      were divided into 2 groups: group I was treated by ORIF with bone grafting (n =
      28) and group II was treated by ORIF without bone grafting (n = 29). The
      radiologic evaluation included Bohler's angle, Gissane's angle, and the height
      and width of the calcaneum. In addition, the American Orthopaedic Foot and Ankle
      Society questionnaires and visual analog scale were completed by the patients.
      During the follow-up period, no differences were found in the outcome measures
      (Bohler's angle, p = .447; Gissane's angle, p = .599; calcaneal height, p = .065;
      calcaneal width p = .077; and American Orthopaedic Foot and Ankle Society
      questionnaires, p = .282) with or without bone grafting. The only difference
      between the 2 groups was the occurrence of postoperative pain (p = .024 and p =
      <= .05), which was greater in the patients who had undergone bone grafting. We
      have provided evidence that bone grafting with internal fixation in the treatment
      of intraarticular calcaneal fractures failed to improve the restoration of
      Bohler's angle or Gissane's angle. No statistically significant difference was
      found in the short-term outcomes between the 2 methods used for the surgical
      treatment of Sanders type III calcaneal fractures.

PMID- 29037928
TI  - Melanoma of the Foot Is Associated With Advanced Disease and Poorer Survival.
AB  - The purpose of the present study was to review the outcomes and assess the
      prognostic factors associated with foot melanoma. We hypothesized that primary
      melanoma of the foot would be more likely to present at an advanced stage and be
      associated with poorer outcomes. Both univariate and multivariate analyses were
      conducted to examine the relationships between patients' demographic, clinical,
      and pathologic characteristics and deaths within 5 years. Categorical data were
      summarized as frequencies and percentages and continuous variables as mean +/-
      standard deviation. The primary outcome measure was overall survival. On
      univariate analysis, the significant prognostic variables found included Breslow
      thickness, ulceration, sentinel node positivity, and localized presentation on
      the toe. Age, sex, and race were not prognostically significant in this model.
      Multivariate Cox proportional hazards analysis resulted in a model of foot
      melanoma with ulceration and location on the toe as independent prognostic
      variables. The 5-year survival rate for melanoma of the toe was 50%. The results
      of the present study have shown that physicians should have a low threshold to
      biopsy suspicious lesions of the foot and ankle. Advanced disease and poorer
      survival were noted with toe melanoma. An ulcerative lesion of the foot was also
      associated with poorer survival.

PMID- 29037929
TI  - Severe Sepsis and Acute Myocardial Dysfunction in an Adolescent with Chlamydia
      Trachomatis Pelvic Inflammatory Disease: A Case Report.
AB  - BACKGROUND: Although generally asymptomatic, severe Chlamydia trachomatis (C.
      trachomatis) infections have been documented. C. trachomatis has been associated
      with myocarditis as well as sepsis. CASE: A 19-year-old girl with type 1 diabetes
      mellitus developed sudden-onset mental status change and shock after resolution
      of diabetic ketoacidosis. Abdominal and pelvic imaging showed uterine and adnexal
      inflammation, and pelvic examination confirmed a diagnosis of pelvic inflammatory
      disease. The patient was intubated, required vasopressor support, and developed
      severe biventricular myocardial dysfunction. Infectious myocarditis workup was
      negative. Nucleic acid amplification testing from vaginal discharge was positive
      for C. trachomatis and Trichomonas vaginalis and negative for Neisseria
      gonorrhoeae. SUMMARY AND CONCLUSION: C. trachomatis should be considered in the
      workup of septic shock, particularly in populations at high risk for sexually
      transmitted infections.

PMID- 29037930
TI  - Adolescent-Parent Dyad Descriptions of the Decision to Start the HPV Vaccine
      Series.
AB  - STUDY OBJECTIVE: To examine how adolescent-parent dyads describe decision-making
      regarding initiation of the human papillomavirus (HPV) vaccine series,
      specifically who they viewed as making the final decision. DESIGN: Semistructured
      interviews with adolescent-parent dyads were audio-recorded and transcribed.
      Responses to the question: "How did you make a decision about whether or not to
      receive the HPV vaccine series?" were content-coded for each individual member of
      the dyad. SETTING: Adolescent medicine clinics of 2 large urban medical centers
      and through snowball sampling. PARTICIPANTS: Adolescents 14-17 years of age and a
      parent (N = 262). Qualitative analyses were conducted for those who agreed that
      they were offered and started the HPV vaccine series (n = 109). INTERVENTIONS:
      None. MAIN OUTCOME MEASURES: Descriptions of the decision-making included 1
      person (adolescent or parent) making the decision or joint decision-making by the
      adolescent and parent together. RESULTS: More than half of the dyads did not
      agree on who made the decision to start the vaccine. Most adolescents and parents
      described a similar account about when they were offered the HPV vaccine,
      although the interpretation of the event in terms of the decision-maker might
      have differed. More than half of adolescents and parents individually mentioned
      the health care provider in their description of the HPV vaccine decision-making
      process even though they were not queried about the role of the provider.
      CONCLUSION: Understanding the range of descriptions of these dyads is helpful to
      guide interventions to promote vaccine uptake in a manner that balances provider
      expertise, adolescent autonomy, and parental involvement.

PMID- 29037931
TI  - Distinct populations of embryonic epithelial progenitors generate Lgr5+
      intestinal stem cells.
AB  - The adult intestinal stem cells (ISCs) are transcriptionally heterogeneous. As
      the mechanisms governing their developmental specification are still poorly
      understood, whether this heterogeneity reflects an early determination of
      distinct cellular sub-types with potentially distinct physiological functions
      remains an open question. We investigate the cellular heterogeneity within the
      mouse embryonic midgut epithelium at the molecular and functional levels. Cell
      fate mapping analysis revealed that multiple early embryonic epithelial
      progenitors give rise to Lgr5+ ISCs. The origin of the molecularly distinct early
      precursors along the anterior-posterior axis defines the transcriptional
      signature of embryonic Lgr5+ ISC progenitors. We further show that the early
      epithelial progenitors have different capacity to generate Lgr5+ ISC progenitors
      and Axin2+ early precursors display the highest potential.

PMID- 29037934
TI  - The primary diagnosis and the coexisting anxiety disorders have no impact on the
      additional surgical procedure after spinal cord stimulators implantation: An
      analysis of 11,029 patients.
AB  - Studies have demonstrated superior outcomes and cost effectiveness of the spinal
      cord stimulation (SCS) for the treatment of chronic pain syndromes such as failed
      back surgery syndrome (FBSS) or complex regional pain syndrome (CRPS). However,
      little is known about the impact of primary diagnosis or mental disorders on the
      revision rate. This is the Retrospective cohort study to analyze the
      reintervention rates based on the primary diagnosis or comorbid mental disorder.
      Data of the annual trends of SCS use, revision and removal rate of SCS and
      additional surgical rate after removal was collected and analyzed for patients
      undergoing SCS between 2007 and 2015, within a private insurance billing
      database. Trial cases were excluded from this study. The results showed 11,029
      patients received SCS implantation with percutaneous electrodes (PE, n = 7418) or
      surgical electrode (SE, n = 3611). There was a trend of increasing use of SCS
      from 2007 to 2013, followed by a decrease in last two years. There was no
      significant difference in the neither removal nor revision rate regardless
      between the patients with FBSS or CRPS at each time point. Although the removal
      rates within 2 years were significantly higher in the patients with anxiety
      disorders compared to the patients without any mental disorders (PE: p < .001,
      SE: 0.003), the rate of additional surgery after the removal showed no
      significant difference (PE: p = .532, SE: p = .262). Therefore, we concluded that
      the primary diagnosis and the presence of anxiety disorders did not have an
      impact on the additional surgical rate following SCS implantation.

PMID- 29037932
TI  - Retinoic acid deficiency leads to an increase in spermatogonial stem number in
      the neonatal mouse testis, but excess retinoic acid results in no change.
AB  - The onset of spermatogenesis occurs in response to retinoic acid (RA), the active
      metabolite of vitamin A. However, whether RA plays any role during establishment
      of the spermatogonial stem cell (SSC) pool is unknown. Because designation of the
      SSC population and the onset of RA signaling in the testis that induces
      differentiation have similar timing, this study asked whether RA influenced SSC
      establishment. Whole mount immunofluorescence and flow cytometric analysis using
      the Id4-eGfp transgenic reporter mouse line revealed an enrichment for ID4-EGFP+
      cells within the testis following inhibition of RA synthesis by WIN 18,446
      treatment. Transplantation analyses confirmed a significant increase in the
      number of SSCs in testes from RA-deficient animals. Conversely, no difference in
      the ID4-EGFP+ population or change in SSC number were detected following exposure
      to an excess of RA. Collectively, reduced RA altered the number of SSCs present
      in the neonatal testis but precocious RA exposure in the neonatal testis did not,
      suggesting that RA deficiency causes a greater proportion of progenitor
      undifferentiated spermatogonia to retain their SSC state past the age when the
      pool is thought to be determined.

PMID- 29037933
TI  - Role of maternal Xenopus syntabulin in germ plasm aggregation and primordial germ
      cell specification.
AB  - The localization and organization of mitochondria- and ribonucleoprotein granule
      rich germ plasm is essential for many aspects of germ cell development. In
      Xenopus, germ plasm is maternally inherited and is required for the specification
      of primordial germ cells (PGCs). Germ plasm is aggregated into larger patches
      during egg activation and cleavage and is ultimately translocated perinuclearly
      during gastrulation. Although microtubule dynamics and a kinesin (Kif4a) have
      been implicated in Xenopus germ plasm localization, little is known about how
      germ plasm distribution is regulated. Here, we identify a role for maternal
      Xenopus Syntabulin in the aggregation of germ plasm following fertilization. We
      show that depletion of sybu mRNA using antisense oligonucleotides injected into
      oocytes results in defects in the aggregation and perinuclear transport of germ
      plasm and subsequently in reduced PGC numbers. Using live imaging analysis, we
      also characterize a novel role for Sybu in the collection of germ plasm in
      vegetal cleavage furrows by surface contraction waves. Additionally, we show that
      a localized kinesin-like protein, Kif3b, is also required for germ plasm
      aggregation and that Sybu functionally interacts with Kif3b and Kif4a in germ
      plasm aggregation. Overall, these data suggest multiple coordinate roles for
      kinesins and adaptor proteins in controlling the localization and distribution of
      a cytoplasmic determinant in early development.

PMID- 29037935
TI  - The pathogenesis of delayed epidural hematoma after posterior fossa surgery.
AB  - The purpose of this study was to analyze the pathogenesis of delayed epidural
      hematoma (EDH) after posterior fossa surgery. Non-traumatic, non-arterial origin
      delayed EDH after posterior fossa surgery is extremely rare. Moreover, the
      pathogenesis of its supratentorial extension is obscure. Between April 1997 and
      June 2016, over 3300 patients underwent microvascular decompression (MVD) for
      neurovascular compression syndrome. The medical chart of four patients with
      delayed EDH were retrospectively reviewed. The median time from MVD to re-CT scan
      was 58 h (range, 33-100). All patients underwent hematoma evacuations.
      Intraoperative findings during hematoma evacuation revealed only an oozing
      hemorrhage from the transverse sinus with no definitive bleeding focus. The
      patients spent a median of 21.5 days (range, 11-39) at the hospital. At the last
      follow-up, all patients had fully recovered without significant neurological
      deficits and exhibited complete relief or minimal symptoms from hemifacial spasm
      (HFS). Postoperative uncontrolled bleeding from the dural venous sinus can
      sometimes cause an insidious-onset or delayed posterior fossa EDH.

PMID- 29037936
TI  - Super-refractory nonconvulsive status epilepticus due to self-poisoning with
      metaldehyde.
AB  - INTRODUCTION: Metaldehyde self-poisoning in adults is uncommon and, to the best
      of our knowledge, an episode of super-refractory nonconvulsive status epilepticus
      (sr-NCSE) following an suicide attempt has not been previously demonstrated. CASE
      REPORT: A 68-year-old woman was admitted to our Intensive Care Unit (ICU) in
      coma. On neurologic examination, the pupils were reactive, brainstem reflexes
      were present and plantar responses were flexor bilaterally. Routine laboratory
      tests were unremarkable. Arterial blood gas analysis revealed a mixed acidosis. A
      computed tomography (CT) scan of the brain and angio-CT were normal. The family
      confirmed that the patient had had suicidal ideation, and they had discovered a
      bag of slug killer (metaldehyde 5%) in her room. Two hours after the admission at
      the ICU, her neurological state remained unchanged. Sedation with intravenous
      propofol and antiepileptic therapy with levetiracetam (1000 mg/24 h) were
      started. The next day, propofol infusion was stopped but the level of
      consciousness of the patient did not improve. A video-electroencephalograhy (v
      EEG) showed continuous generalized paroxysms of spike-wave and sharp-slow wave
      complexes compatible with the diagnosis of generalized NCSE. On day 3, the
      episode of NCSE was controlled. Finally, 15 days after ICU admission she was
      discharged with a normal neurological examination. CONCLUSION: This clinical case
      highlights that in comatose patients as consequence of metaldehyde poisoning, a v
      EEG evaluation should be perform in order to rule out the existence of NCSE.

PMID- 29037937
TI  - Treatment advances in Parkinson disease: Same script different cast?

PMID- 29037938
TI  - Non-Clostridium difficile Bacterial Infections Are Rare in Patients With Flares
      of Inflammatory Bowel Disease.
AB  - BACKGROUND & AIMS: Clostridium difficile infection (CDI) causes flares in
      patients with inflammatory bowel disease (IBD). We investigated the frequency and
      outcomes of non-CDI bacterial enteric infections in symptomatic patients with
      IBD. METHODS: We performed a retrospective study of patients with ulcerative
      colitis (UC) or Crohn's disease (CD) from whom stool samples were collected and
      analyzed by PCR or culture for bacterial pathogens (Campylobacter jejuni or C
      coli, Salmonella species, Shigella species, enteroinvasive Escherichia coli,
      shiga toxin-producing E coli, or Yersinia species) from November 19, 2011,
      through June 30, 2014. Patients were excluded if they had nonbacterial infections
      or no symptoms. Data were collected from medical records on IBD duration,
      treatment, age at diagnosis, and presence of concurrent CDI. Patients were
      followed for 1 year after the date of infection resolution or until date of last
      follow-up in the health record. Each patient with an enteric infection was
      matched with 2 patients with IBD flares and negative results from stool tests
      (non-infected control) and 2 patients with IBD and CDI (CDI control), adjusted
      for age (within 5 years at the time of stool test), sex, and IBD subtype. Outcome
      measures included IBD therapy escalation and hospitalization. RESULTS: Of 9247
      patients with IBD seen during the study period, stool samples were tested from
      1345 patients (50% with UC and 50% with CD). There were 3 positive results
      (detection of bacterial pathogens) from 339 PCR analyses of stool samples from
      296 patients with UC (0.88%) and 12 positive results from 486 cultures of stool
      samples from 418 patients with UC (2.5%). There was 1 positive result from 355
      PCR analyses of stool samples from 311 patients with CD (0.28%) and 9 positive
      results from 496 cultures of stool samples from 413 patients with CD (1.8%). Of
      the 19 patients followed beyond infection, 9 patients required escalation of
      their IBD therapy (47%)-most commonly addition of an immunomodulator (5 patients)
      or a biological agent (3 patients)-compared with 34% of CDI controls and 66% of
      non-infected controls (P < .001). Higher proportions of patients with non-CDI
      bacterial infections were in remission 1 year after their infection (89%) than
      patients with CDI (55%) or negative results of stool tests (63%; P = .04). We did
      not observe differences in hospitalization, emergency department visits, or
      surgical interventions among groups. CONCLUSIONS: In a retrospective study of
      patients with an IBD flare, we detected non-CDI bacterial infections in fewer
      than 3% of those who were tested. Higher proportions of patients with non-CDI
      bacterial infections were in remission in the year after their infection than
      patients with CDI.

PMID- 29037939
TI  - Relationship of Hospital Teaching Status with In-Hospital Outcomes for ST-Segment
      Elevation Myocardial Infarction.
AB  - BACKGROUND: Prior analyses have largely shown a survival advantage with admission
      to a teaching hospital for acute myocardial infarction. However, most prior
      studies report data on patients hospitalized over a decade ago. It is important
      to re-examine the association of hospital teaching status with outcomes of acute
      myocardial infarction in the current era. METHODS: We queried the 2010 to 2014
      National Inpatient Sample databases to identify all patients aged >=18 years
      hospitalized with the principal diagnosis of ST-segment elevation myocardial
      infarction (STEMI). Multivariable logistic regression models were constructed to
      compare rates of reperfusion and in-hospital outcomes between patients admitted
      to teaching vs nonteaching hospitals. RESULTS: Of 546,252 patients with STEMI,
      273,990 (50.1%) were admitted to teaching hospitals. Compared with patients
      admitted to nonteaching hospitals, those at teaching hospitals were more likely
      to receive reperfusion therapy during the hospitalization (86.7% vs 81.5%;
      adjusted odds ratio [OR] 1.41; 95% confidence interval [CI], 1.39-1.44; P < .001)
      and had lower risk-adjusted in-hospital mortality (4.9% vs 6.9%; adjusted OR
      0.84; 95% CI, 0.82-0.86; P < .001). After further adjustment for differences in
      use of in-hospital reperfusion therapy, the association of teaching hospital
      status with lower risk-adjusted in-hospital mortality was significantly
      attenuated but remained statistically significant (adjusted OR 0.97; 95% CI, 0.94
      0.99; P = .02). CONCLUSIONS: Patients admitted to teaching hospitals are more
      likely to receive reperfusion and have lower risk-adjusted in-hospital mortality
      after STEMI compared with those admitted to nonteaching hospitals. Our results
      suggest that hospital performance for STEMI continues to be better at teaching
      hospitals in the contemporary era.

PMID- 29037940
TI  - Hyperbaric oxygen treatment effects on in vitro cultured umbilical cord blood
      CD34+ cells.
AB  - BACKGROUND AIMS: Umbilical cord blood (UCB) provides an alternative source for
      hematopoietic stem/progenitor cells (HSPCs) in the treatment of hematological
      malignancies. However, clinical usage is limited due to the low quantity of HSPCs
      in each unit of cord blood and defects in bone marrow homing. Hyperbaric oxygen
      (HBO) is among the more recently explored methods used to improve UCB homing and
      engraftment. HBO works by lowering the host erythropoietin before UCB infusion to
      facilitate UCB HSPC homing, because such UCB cells are not directly exposed to
      HBO. In this study, we examined how direct treatment of UCB-CD34+ cells with HBO
      influences their differentiation, proliferation and in vitro transmigration.
      METHODS: Using a locally designed HBO chamber, freshly enriched UCB-CD34+ cells
      were exposed to 100% oxygen at 2.5 atmospheres absolute pressure for 2 h before
      evaluation of proliferative capacity, migration toward a stromal cell-derived
      factor 1 gradient and lineage differentiation. RESULTS: Our results showed that
      HBO treatment diminishes proliferation and in vitro transmigration of UCB-CD34+
      cells. Treatment was also shown to limit the ultimate differentiation of these
      cells toward an erythrocyte lineage. As a potential mechanism for these findings,
      we also investigated HBO effects on the relative concentration of cytoplasmic and
      nucleic reactive oxygen species (ROS) and on erythropoietin receptor (Epo-R) and
      CXCR4 expression. HBO-treated cells showed a relative increase in nucleic ROS but
      no detectable differences in the level of Epo-R nor CXCR4 expression were
      established compared with non-treated cells. DISCUSSION: In summary, HBO
      amplifies the formation of ROS in DNA of UCB-CD34+ cells, potentially explaining
      their reduced proliferation, migration and erythrocytic differentiation.

PMID- 29037941
TI  - Pre-clinical assessment of the Lovo device for dimethyl sulfoxide removal and
      cell concentration in thawed hematopoietic progenitor cell grafts.
AB  - BACKGROUND: Cryopreserved hematopoietic progenitor cell (HPC) grafts are widely
      infused to patients with malignant and nonmalignant conditions. Despite reduction
      of immediate side effects linked to dimethyl sulfoxide (DMSO), cell debris
      containing grafts and comparable hematopoietic engraftment between washed and
      unwashed cryopreserved products, bedside infusion of thawed HPC grafts is still
      preferred. Introduction of automated devices is important for standardization and
      consistency of graft manipulation. Additionally, these techniques are likely to
      be useful for the delivery of innovative cell-based medicinal products that are
      currently under development. METHODS: In this study, we evaluated three
      consecutive versions of the Lovo device (Fresenius Kabi) for automated washing of
      thawed HPC products. A total of 42 HPC products intended for destruction were
      used. Measured outcomes included viable CD34+ cell recovery, viability, total
      processing time and post-washing stability. RESULTS: Preliminary data using the
      prototype Lovo 0.0 to process a single HPC unit showed better recovery and
      viability of CD34+ cells using a two-cycle than a three-cycle wash, with >95%
      DMSO elimination. The Lovo 1.0 performed equally well. When simultaneously
      processing two HPC units, the upgraded Lovo 2.0 device demonstrated comparable
      CD34+ recovery, DMSO elimination efficiencies and time-saving capacity.
      Furthermore, washed cell products were stable for 4 hours at room temperature.
      DISCUSSION: Lovo device satisfies clinically relevant issues: ability to
      efficiently wash two HPC units simultaneously and compatibility with transport to
      nearby transplantation centers.

PMID- 29037942
TI  - Evaluating the quality of a cell counting measurement process via a dilution
      series experimental design.
AB  - BACKGROUND AIMS: Cell counting measurements are critical in the research,
      development and manufacturing of cell-based products, yet determining cell
      quantity with accuracy and precision remains a challenge. Validating and
      evaluating a cell counting measurement process can be difficult because of the
      lack of appropriate reference material. Here we describe an experimental design
      and statistical analysis approach to evaluate the quality of a cell counting
      measurement process in the absence of appropriate reference materials or
      reference methods. METHODS: The experimental design is based on a dilution series
      study with replicate samples and observations as well as measurement process
      controls. The statistical analysis evaluates the precision and proportionality of
      the cell counting measurement process and can be used to compare the quality of
      two or more counting methods. As an illustration of this approach, cell counting
      measurement processes (automated and manual methods) were compared for a human
      mesenchymal stromal cell (hMSC) preparation. RESULTS: For the hMSC preparation
      investigated, results indicated that the automated method performed better than
      the manual counting methods in terms of precision and proportionality.
      DISCUSSION: By conducting well controlled dilution series experimental designs
      coupled with appropriate statistical analysis, quantitative indicators of
      repeatability and proportionality can be calculated to provide an assessment of
      cell counting measurement quality. This approach does not rely on the use of a
      reference material or comparison to "gold standard" methods known to have limited
      assurance of accuracy and precision. The approach presented here may help the
      selection, optimization, and/or validation of a cell counting measurement
      process.

PMID- 29037943
TI  - Mesenchymal stromal cells protect human cardiomyocytes from amyloid fibril
      damage.
AB  - BACKGROUND AIMS: Light chain (AL) amyloidosis is a protein misfolding disease
      characterized by extracellular deposition of immunoglobulin light chains (LC) as
      amyloid fibrils. Patients with LC amyloid involvement of the heart have the worst
      morbidity and mortality. Current treatments target the plasma cells to reduce
      further production of amyloid proteins. There is dire need to understand the
      mechanisms of cardiac tissue damage from amyloid to develop novel therapies. We
      recently reported that LC soluble and fibrillar species cause apoptosis and
      inhibit cell growth in human cardiomyocytes. Mesenchymal stromal cells (MSCs) can
      promote wound healing and tissue remodeling. The objective of this study was to
      evaluate MSCs to protect cardiomyocytes affected by AL amyloid fibrils. METHODS:
      We used live cell imaging and proteomics to analyze the effect of MSCs in the
      growth arrest caused by AL amyloid fibrils. RESULTS: We evaluated the growth of
      human cardiomyocytes (RFP-AC16 cells) in the presence of cytotoxic LC amyloid
      fibrils. MSCs reversed the cell growth arrest caused by LC fibrils. We also
      demonstrated that this effect requires cell contact and may be mediated through
      paracrine factors modulating cell adhesion and extracellular matrix remodeling.
      To our knowledge, this is the first report of MSC protection of human
      cardiomyocytes in amyloid disease. CONCLUSIONS: This important proof of concept
      study will inform future rational development of MSC therapy in cardiac LC
      amyloid.

PMID- 29037944
TI  - Identification of pyrrolo[2,3-d]pyrimidines as potent HCK and FLT3-ITD dual
      inhibitors.
AB  - A series of novel pyrrolo[2,3-d]pyrimidines were synthesized by introducing 15
      different amino acids to 7-cyclohexyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3
      d]pyrimidine-4-amine. Compounds with potent activities against HCK and FLT3-ITD
      were evaluated in viability studies with acute myeloid leukemia cell line MV4-11.
      Our structure activity relationship analyses lead to the identification of
      compound 31, which exhibited potent HCK and FLT3-ITD inhibition and activity
      against the MV4-11 cell line.

PMID- 29037945
TI  - Enantioselective inhibitory abilities of enantiomers of notoamides against RANKL
      induced formation of multinuclear osteoclasts.
AB  - The marine-derived Aspergillus protuberus MF297-2 and the terrestrial A. amoenus
      NRRL 35600 produce enantiomeric prenylated indole alkaloids. Investigation of
      biological activities of the natural and synthetic derivatives revealed that (-)
      enantiomers of notoamides A and B, 6-epi-notoamide T, and stephacidin A inhibited
      receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL)-induced
      osteoclastogenic differentiation of murine RAW264 cells more strongly than their
      respective (+)-enantiomers. Among them, (-)-6-epi-notoamide T was the most potent
      inhibitor with an IC50 value of 1.7MUM.

PMID- 29037946
TI  - Discovery of a novel 2,4-dimethylquinoline-6-carboxamide M4 positive allosteric
      modulator (PAM) chemotype via scaffold hopping.
AB  - This Letter details our efforts to replace the 3-amino moiety, an essential
      pharmacophore for M4 PAM activity in most M4 PAMs to date, within the thieno[2,3
      b]pyridine core, as the beta-amino carboxamide motif has been shown to engender
      poor solubility, varying degrees of P-gp efflux and represents a structural
      alert. A scaffold hopping exercise identified a novel 2,4-dimethylquinoline
      carboxamide core that provided M4 PAM activity and good CNS penetration without
      an amino moiety. In addition, MacMillan photoredox catalysis chemistry was
      essential for construction of the 2,4-dimethylquinoline core.

PMID- 29037947
TI  - Discovery of benzo[g]indoles as a novel class of non-covalent Keap1-Nrf2 protein
      protein interaction inhibitor.
AB  - The Keap1-Nrf2 system is an attractive target for drug discovery regarding
      various unmet medical needs. Only covalent inhibitors for protein-protein
      interaction (PPI) between Keap1 and Nrf2 to activate Nrf2 have been approved or
      are under clinical trials, but such electrophilic compounds lack selectivity.
      Therefore, specific non-covalent Keap1-Nrf2 PPI inhibitors are expected to be
      safer Nrf2 activators. We found a novel class of non-covalent Keap1-Nrf2 PPI
      inhibitor that has a benzo[g]indole skeleton and an indole-3-hydroxamic acid
      moiety and that exhibits significant PPI inhibitory activity. Additionally, the
      benzo[g]indole-3-carbohydrazide derivatives were newly prepared. The
      benzo[g]indole derivatives showed a stronger Keap1-Nrf2 PPI inhibitory activity
      than Cpd16, a previously reported non-covalent PPI inhibitor. Moreover, most of
      the PPI inhibitors showed a high metabolic stability in a human microsome system
      with a low cytotoxicity against HepG2 cell lines, which suggests that novel
      benzo[g]indole-type Keap1-Nrf2 PPI inhibitors are expected to be biological tools
      or lead compounds for Nrf2 activators.

PMID- 29037948
TI  - Discovery of aminocyclohexene analogues as selective and orally bioavailable
      hNav1.7 inhibitors for analgesia.
AB  - hNav1.7 receives a lot of attention owing to its attractive mechanism of action
      in pain processing pathway. We have previously reported our design of a novel
      series of tetrahydropyridine analogues towards hNav1.7 selective inhibitors.
      Herein, we disclose further efforts to the optimization of hit compound (-)-6,
      which led to the identification of aminocyclohexene analogues (-)-9 and (-)-17
      with good potency, high selectivity, and minimal CYP inhibition. Both compounds (
      )-9 and (-)-17 demonstrated improved pharmacokinetic profiles in rats, and robust
      efficacy in rat formalin-induced nociception and spinal nerve ligation (SNL)
      models.

PMID- 29037949
TI  - Antibacterial activities of viriditoxin congeners and synthetic analogues against
      fish pathogens.
AB  - Viriditoxin is a fungal secondary metabolite of the fungus Paecilomyces variotii
      derived from the inner tissues of the giant jellyfish Nemopilema nomurai.
      Viriditoxin exhibits antibacterial activity against Streptococcus iniae and
      Streptococcus parauberis, which are major pathogens of aqua cultured fish.
      Viriditoxin induced abnormal cell morphologies in the fish pathogens S. iniae and
      S. parauberis, presumably by inhibiting FtsZ polymerization as was previously
      observed in Escherichia coli. Synthetic analogues of viriditoxin, designed based
      on docking simulation results to FtsZ of Staphylococcus aureus, were prepared and
      compared with viriditoxin for antibacterial activity. Reconstitution of free
      hydroxyl or carboxyl groups of the methoxyl or methyl ester groups of viriditoxin
      led to significant reduction of antibacterial activity, implying that the natural
      molecule is optimized for antibacterial activity to deter bacteria potentially
      harmful to Paecilomyces.

PMID- 29037950
TI  - Discovery of tranylcypromine analogs with an acylhydrazone substituent as LSD1
      inactivators: Design, synthesis and their biological evaluation.
AB  - Lysine specific demethylase 1 (LSD1), the first identified histone demethylase,
      plays an important role in epigenetic regulation of gene activation and
      repression, has been reported to be up-regulated and involved in numbers of solid
      malignant tumors. In this study, we identified a series of phenylalanyl
      hydrazones based LSD1 inhibitors, and the most potent one, compound 4q, can
      inactivate LSD1 with IC50 = 91.83 nM. In cellular level, compound 4q can induce
      the accumulation of CD86 as well as H3K4me2, and inhibit gastric cancer cell
      proliferation by inactivating LSD1. Our findings indicated that compound 4q may
      serve as a potential leading compound to target LSD1 overexpressed gastric
      cancer.

PMID- 29037951
TI  - Design and synthesis of novel nitrogen mustard-evodiamine hybrids with selective
      antiproliferative activity.
AB  - A series of novel nitrogen mustard-evodiamine hybrids were synthesized and
      evaluated for their antitproliferative properties. The antiproliferative
      activities of 10a-d, 11a-d, and 12a-d against four different kinds of human
      cancer cell lines (PC-3, HepG2, THP-1 and HL-60) and human normal peripheral
      blood mononuclear cells (PBMC) were determined. The results showed that all the
      target hybrid compounds exhibited antiproliferative activities against tested
      human tumor cell lines to some extent and no antiproliferative activities (>200
      MUM) against human normal PBMC cells. The antiproliferative selectivity between
      tumorous and normal cells was very useful for further antitumor drug development.
      Among the target compounds, 12c showed the strongest cytotoxicity against two
      tumor cell lines (THP-1 and HL-60) with IC50 values of 4.05 MUM and 0.50 MUM,
      respectively, and selected for further mechanism study in HL-60 cells. The
      results showed that 12c could induce HL-60 cells apoptosis and arrest at G2 phase
      at low sub-micromolar concentrations via mitochondria-related pathways.

PMID- 29037952
TI  - [Phenotype variability in thirteen 16p11.2 deletion patients].

PMID- 29037953
TI  - [High-frequency users of Emergency Departments. Experience and failure of health
      education counselling].

PMID- 29037954
TI  - [Hematemesis as debut of eosinophilic gastroenteritis in infants].

PMID- 29037955
TI  - Single Molecule Arrays for ultra-sensitive detection of rat cytokines in serum.
AB  - Rats are used as animal models for many human diseases. Cytokines can serve as
      biomarkers indicative of these diseases or disease states. Techniques for
      measuring cytokine expression levels often do not provide the sensitivity needed
      to measure these biomarkers in biological fluids because the concentrations of
      many cytokines are below the detection limits of conventional methods. In this
      paper, we present ultra-sensitive digital immunoassays using Single Molecule
      Arrays (Simoa) for seven rat cytokines: TNF-alpha, IL-10, IL-17F, GM-CSF, IFN
      gamma, IL-4, and IL-1alpha. These ultra-sensitive immunoassays have limits of
      detection (LODs) in the femtomolar range and provide the ability to measure rat
      cytokines in serum below the LODs of conventional immunoassays. We also measured
      these cytokines in healthy rat serum to obtain baseline levels. The ability to
      measure cytokines present at low concentrations in rat serum will facilitate
      future studies of disease using rats as animal models.

PMID- 29037956
TI  - A simple and cost-effective assay for measuring anti-drug antibody in human
      patients treated with Adalimumab.
AB  - It has been reported that 90% of the anti-drug antibody (ADA) to Adalimumab in
      human patients bound to the TNF-binding area, resulted in the annual loss of
      responses to Adalimumab up to 24%. It is of urgency to develop a cost-effective
      and easy-to-use ADA diagnostic kit for diagnosis of potential drug-resistance in
      patients treated with Adalimumab in clinic hospitals to avoid the tremendous
      economic and human costs to patients and health-care providers. In this study, we
      reported the generations of mouse monoclonal and monkey polyclonal antibodies
      against Adalimumab as assay standards and positive quality controls respectively.
      A Bridging ELISA assay was successfully developed with a limit of detection (LOD)
      between 22-80ng/ml. The preliminary validation of assay was carried out first
      with 50 normal human sera, further validated by screening the ADA in 192 serum
      samples from monkeys treated with or without Adalimumab. Our data showed that the
      Bridging ELISA kit is very sensitive, highly specific and ready for study in
      human clinic trials.

PMID- 29037957
TI  - Magnetic Resonance Imaging in People With Cardiac Implantable Electronic Devices:
      A Population Based Cohort Study.
AB  - Magnetic resonance imaging (MRI) is a widely used diagnostic tool with great
      benefits but has been considered contraindicated in people with cardiac
      implantable electronic devices (CIED). We investigated the occurrence of MRI in
      people with CIEDs and associated adverse events in a national cohort. Of 17,848
      people included, 56 (0.3%) had at least one MRI; 16 of 16,102 (0.1%) with MRI non
      compatible CIEDs and 40 of 1746 (2%) with MRI compatible CIEDs. Following MRI
      exposure, hospitalisations for potential serious adverse events were rare.

PMID- 29037959
TI  - Procalcitonin and antibiotic use: imperfect, yet effective.

PMID- 29037958
TI  - Expression of PD-1 and PD-L1 in poorly differentiated neuroendocrine carcinomas
      of the digestive system: a potential target for anti-PD-1/PD-L1 therapy.
AB  - Poorly differentiated neuroendocrine carcinoma of the digestive system has a
      dismal prognosis with limited treatment options. This study aimed to investigate
      expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with
      a poorly differentiated neuroendocrine carcinoma of the digestive system were
      identified. Their electronic medical records, pathology reports, and pathology
      slides were reviewed for demographics, clinical history, and pathologic features.
      Tumor sections were immunohistochemically labeled for PD-1 and PD-L1, and
      expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was
      analyzed and compared between small cell and large cell neuroendocrine
      carcinomas. The mean age of patients was 61 years old with 18 men and 19 women.
      The colorectum (n=20) was the most common primary site; other primary sites
      included the pancreaticobiliary system, esophagus, stomach, duodenum, and
      ampulla. Expression of PD-1 was detected on tumor cells (n=6, 16%) as well as on
      tumor-associated immune cells (n=23, 63%). The 6 cases with PD-1 expression on
      tumor cells also had the expression on immune cells. Expression of PD-L1 was
      visualized on tumor cells in 5 cases (14%) and on tumor-associated immune cells
      in 10 cases (27%). There was no difference in PD-1 and PD-L1 expression between
      small cell and large cell neuroendocrine carcinomas. In conclusion, PD-1/PD-L1
      expression is a frequent occurrence in poorly differentiated neuroendocrine
      carcinomas of the digestive system. Checkpoint blockade targeting the PD-1/PD-L1
      pathway may have a potential role in treating patients with this disease.

PMID- 29037961
TI  - GADD45 family proteins suppress JNK signaling by targeting MKK7.
AB  - Growth arrest and DNA damage-inducible 45 (GADD45) family genes encode related
      proteins, including GADD45alpha, GADD45beta, and GADD45gamma. In HeLa cells,
      expression of GADD45 members is differentially regulated under a variety of
      environmental conditions, but thermal and genotoxic stresses induce the
      expression of all genes. The heat shock response of GADD45beta is mediated by the
      heat shock transcription factor 1 (HSF1), and GADD45beta is necessary for heat
      stress survival. Heat and genotoxic stress-induced activation of c-Jun N-terminal
      kinase (JNK) is suppressed by the expression of GADD45 proteins. GADD45 proteins
      bind the JNK kinase mitogen-activated protein kinase kinase 7 (MKK7) and inhibit
      its activity, even under normal physiological conditions. Our findings indicate
      that GADD45 essentially suppresses the MKK7-JNK pathway and suggest that
      differentially expressed GADD45 family members fine-tune stress-inducible JNK
      activity.

PMID- 29037960
TI  - Effect of procalcitonin-guided antibiotic treatment on mortality in acute
      respiratory infections: a patient level meta-analysis.
AB  - BACKGROUND: In February, 2017, the US Food and Drug Administration approved the
      blood infection marker procalcitonin for guiding antibiotic therapy in patients
      with acute respiratory infections. This meta-analysis of patient data from 26
      randomised controlled trials was designed to assess safety of procalcitonin
      guided treatment in patients with acute respiratory infections from different
      clinical settings. METHODS: Based on a prespecified Cochrane protocol, we did a
      systematic literature search on the Cochrane Central Register of Controlled
      Trials, MEDLINE, and Embase, and pooled individual patient data from trials in
      which patients with respiratory infections were randomly assigned to receive
      antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or
      control. The coprimary endpoints were 30-day mortality and setting-specific
      treatment failure. Secondary endpoints were antibiotic use, length of stay, and
      antibiotic side-effects. FINDINGS: We identified 990 records from the literature
      search, of which 71 articles were assessed for eligibility after exclusion of 919
      records. We collected data on 6708 patients from 26 eligible trials in 12
      countries. Mortality at 30 days was significantly lower in procalcitonin-guided
      patients than in control patients (286 [9%] deaths in 3336 procalcitonin-guided
      patients vs 336 [10%] in 3372 controls; adjusted odds ratio [OR] 0.83 [95% CI
      0.70 to 0.99], p=0.037). This mortality benefit was similar across subgroups by
      setting and type of infection (pinteractions>0.05), although mortality was very
      low in primary care and in patients with acute bronchitis. Procalcitonin guidance
      was also associated with a 2.4-day reduction in antibiotic exposure (5.7 vs 8.1
      days [95% CI -2.71 to -2.15], p<0.0001) and a reduction in antibiotic-related
      side-effects (16% vs 22%, adjusted OR 0.68 [95% CI 0.57 to 0.82], p<0.0001).
      INTERPRETATION: Use of procalcitonin to guide antibiotic treatment in patients
      with acute respiratory infections reduces antibiotic exposure and side-effects,
      and improves survival. Widespread implementation of procalcitonin protocols in
      patients with acute respiratory infections thus has the potential to improve
      antibiotic management with positive effects on clinical outcomes and on the
      current threat of increasing antibiotic multiresistance. FUNDING: National
      Institute for Health Research.

PMID- 29037963
TI  - Conversion between noise exposure indicators Leq24h, LDay, LEvening, LNight, Ldn
      and Lden: Principles and practical guidance.
AB  - This article presents empirically derived conversion rules between the
      environmental noise exposure metrics Leq24h, LDay, LEvening, LNight, Ldn, and
      Lden for the noise sources road, rail and air traffic. It caters to researchers
      that need to estimate the value of one (unknown) noise metric from the value of
      another (known) metric, e.g. in the scope of epidemiological meta-analyses or
      systematic reviews, when results from different studies are pooled and need to be
      related to one common exposure metric. Conversion terms are derived using two
      empirical methods a) based on analyzing the diurnal variation of traffic, and b)
      by analyzing differences between calculated noise exposure metrics. For a) we
      collected and analyzed diurnal traffic share data from European and US airports
      as well as data on the diurnal variation of traffic from roads in several
      European countries and from railway lines in Switzerland which were derived from
      counting stations and official records. For b) we calculated differences between
      noise metrics in over 50'000 stratified randomly sampled dwellings in
      Switzerland. As a result of this exercise, conversion terms, including
      uncertainty estimates, are systematically tabulated for all variants of the
      target metrics. Guidance as to the practical applicability of the proposed
      conversions in different contexts is provided, and limitations of their use are
      discussed.

PMID- 29037962
TI  - Mild palmitate treatment increases mitochondrial mass but does not affect
      EA.hy926 endothelial cells viability.
AB  - A dyslipidaemia-related increase of the concentration of long-chain fatty acids
      in the plasma is an important pathological factor substantially increasing risk
      of serious consequences in vascular endothelium. Inflammatory response,
      atherosclerosis and insulin resistance seem the most severe. Palmitate at
      excessive concentrations has been shown to have a harmful effect on endothelial
      cells impairing NO generation, stimulating reactive oxygen species (ROS)
      formation and affecting their viability. On the other hand we found that
      palmitate applied for 48 h at 100 MUM concentration which is sufficient to induce
      inflammatory response, increase ROS generation and reduce insulin sensitivity of
      EA.hy926 cells, unexpectedly also stimulates NO synthesis and increases
      mitochondrial mass, suggesting a pro-survival rather than anti-survival effect.
      This finding unveils a potential protective mechanism allowing cells to maintain
      their energy homeostasis under conditions of a moderate deregulation of lipid
      metabolism.

PMID- 29037964
TI  - Laparoscopic treatment for stranguled obturator hernia (with video).

PMID- 29037965
TI  - Prostate cancer-specific PET radiotracers: A review on the clinical utility in
      recurrent disease.
AB  - Prostate cancer-specific positron emission tomography (pcPET) has been shown to
      detect sites of disease recurrence at serum prostate-specific antigen (PSA)
      levels that are lower than those levels detected by conventional imaging.
      Commonly used pcPET radiotracers in the setting of biochemical recurrence are
      reviewed including carbon 11/fludeoxyglucose 18 (F-18) choline, gallium 68/F-18
      prostate-specific membrane antigen (PSMA), and F-18 fluciclovine. Review of the
      literature generally favors PSMA-based agents for the detection of recurrence as
      a function of low PSA levels. Positive gallium 68/F-18 PSMA positron emission
      tomography/computed tomography scans detected potential sites of recurrence in a
      median 51.5% of patients when PSA level is <1.0 ng/mL, 74% of patients when PSA
      level is 1.0 to 2.0 ng/mL, and 90.5% of patients when PSA level is >2.0 ng/mL.
      Review of carbon 11/fludeoxyglucose 18 (F-18) choline and F-18 fluciclovine data
      commonly demonstrated lower detection rates for each respective PSA cohort,
      although with some important caveats, despite having similar operational
      characteristics to PSMA-based imaging. Sensitive pcPET imaging has provided new
      insight into the early patterns of disease spread, which has prompted judicious
      reconsideration of additional local therapy after either prostatectomy,
      definitive radiation therapy, or postprostatectomy radiation therapy. This review
      discusses the literature, clinical utility, availability, and fundamental
      understanding of pcPET imaging needed to improve clinical practice.

PMID- 29037966
TI  - Author Response: Congenital Toxoplasmosis, Cytomegalovirus, and Zika Virus
      Infections: Emphasis on the Role of Neuroimaging in Screening, Prognostication,
      and Follow-Up.

PMID- 29037967
TI  - Congenital Toxoplasmosis, Cytomegalovirus, and Zika Virus Infections.

PMID- 29037968
TI  - Recidive metastatique d'un cancer de la vulve sur la cheville.

PMID- 29037969
TI  - Recurrent Vulvar Cancer on the Ankle.

PMID- 29037971
TI  - To fight or mate? Hormonal control of sex recognition, male sexual behavior and
      aggression in the gecko lizard.
AB  - Squamate reptiles are a highly diversified vertebrate group with extensive
      variability in social behavior and sexual dimorphism. However, hormonal control
      of these traits has not previously been investigated in sufficient depth in many
      squamate lineages. Here, we studied the hormonal control of male sexual behavior,
      aggressiveness, copulatory organ (hemipenis) size and sex recognition in the
      gecko Paroedura picta, comparing ovariectomized females, ovariectomized females
      treated with exogenous dihydrotestosterone (DHT), ovariectomized females treated
      with exogenous testosterone (T), control females and males. The administration of
      both T and DHT led to the expression of male-typical sexual behavior in females.
      However, in contrast to T, increased circulating levels of DHT alone were not
      enough to initiate the full expression of male-typical offensive aggressive
      behavior and development of hemipenes in females. Ovariectomized females were as
      sexually attractive as control females, which does not support the need for the
      demasculinization of the cues used for sex recognition by ovarian hormones as
      suggested in other sauropsids. On the other hand, our results point to the
      masculinization of the sex recognition cues by male gonadal androgens.
      Previously, we also demonstrated that sexually dimorphic growth is controlled by
      ovarian hormones in P. picta. Overall, it appears that individual behavioral and
      morphological sexually-dimorphic traits are controlled by multiple endogenous
      pathways in this species. Variability in the endogenous control of particular
      traits could have permitted their disentangling during evolution and the
      occurrence of (semi)independent changes across squamate phylogeny.

PMID- 29037973
TI  - Comparison of anterior and posterior vertebral column resection versus anterior
      and posterior spinal fusion for severe and rigid scoliosis.
AB  - BACKGROUND CONTEXT: Many different correction methods have been reported to treat
      severe and rigid scoliosis. In the past, anterior and posterior spinal fusion
      (APSF), which included an anterior release followed by posterior instrumented
      fusion, was widely applied. In recent years, anterior/posterior vertebral column
      resection (APVCR) is used to treat severe and rigid scoliosis. PURPOSE: We aimed
      to compare the clinical results of APSF and APVCR for severe and rigid scoliosis.
      STUDY DESIGN: This is a retrospective, one-center, institutional review board
      approved study. PATIENT SAMPLE: A total of 48 patients with severe and rigid
      scoliosis treated by APSF or APVCR were enrolled. OUTCOME MEASURES: Comparisons
      between groups were made regarding the following variables: age at surgery,
      gender, etiology, flexibility of main curve, anterior release length, posterior
      fusion length, screw number, operation time, estimated blood loss,
      hospitalization time, follow-up duration, different radiological parameters,
      complication rate, and Scoliosis Research Society (SRS)-22 scores. METHODS:
      According to the operating technique, 48 patients with severe and rigid scoliosis
      were divided into two groups. In the first group, 26 patients were treated by
      APSF. In the second group, 22 patients were treated by APVCR. All patients had a
      minimum 2-year follow-up. The radiographic parameters as well as anterior release
      length, posterior fusion length, screw number, operation time, estimated blood
      loss, hospitalization time, complication rate, and demographic data were
      analyzed. RESULTS: There was no significant difference in age, gender, etiology,
      flexibility of main curve, anterior release length, posterior fusion length,
      screw number, and follow-up between the two groups. The APVCR group had longer
      operation and hospitalization time, and more blood loss. There was no significant
      difference in the preoperative main curve between the two groups, but the APVCR
      group had smaller main curve at postoperation and final follow-up, and higher
      correction rate at immediate postoperation and final follow-up. There was no
      significant difference in the preoperative, postoperative, and final follow-up
      thoracic kyphosis, and coronal and sagittal balance between the two groups. There
      was no significant difference in complication rate between the two groups.
      Analysis of the preoperative SRS-22 questionnaire revealed no difference between
      the two groups. At final follow-up, APSF and APVCR groups had similar scores in
      the function, pain, self-image, mental health, and satisfaction with the
      treatment domains. CONCLUSIONS: Compared with APSF, treating severe and rigid
      scoliosis by APVCR means longer operation and hospitalization time, and more
      blood loss, but it allows better correction rate of main curve. Furthermore, SRS
      22 questionnaire improvement scores were similar for both correction methods.

PMID- 29037972
TI  - Sex differences in circuits activated by corticotropin releasing factor in rats.
AB  - Women are more likely than men to suffer from psychiatric disorders characterized
      by corticotropin releasing factor (CRF) hypersecretion, suggesting sex
      differences in CRF sensitivity. In rodents, sex differences in the sensitivity of
      specific brain regions to CRF have been identified. However, regions do not work
      in isolation, but rather form circuits to coordinate distinct responses to
      stressful events. Here we examined whether CRF activates different circuits in
      male and female rats. Following central administration of CRF or artificial
      cerebrospinal fluid (aCSF), neuronal activation in stress-related areas was
      assessed using cFOS. Functional connectivity was gauged by correlating the number
      of cFOS-positive cells between regions and then identifying differences within
      each sex in correlations for aCSF-treated and CRF-treated groups. This analysis
      revealed that CRF altered different circuits in males and females. As an example,
      CRF altered correlations involving the dorsal raphe in males and the bed nucleus
      of the stria terminalis in females, suggesting sex differences in stress
      activated circuits controlling mood and anxiety. Next, plasma estradiol and
      progesterone levels were correlated with cFOS counts in females. Negative
      correlations between estradiol and neuronal activation in the regions within the
      extended amygdala were found in CRF-treated, but not aCSF-treated females. This
      result suggests that estrogens and CRF together modulate the fear and anxiety
      responses mediated by these regions. Collectively, these studies reveal sex
      differences in the way brain regions work together in response to CRF. These
      differences could drive different stress coping strategies in males and females,
      perhaps contributing to sex biases in psychopathology.

PMID- 29037974
TI  - Impact of early unanticipated revision surgery on health-related quality of life
      after adult spinal deformity surgery.
AB  - BACKGROUND CONTEXT: Revision surgery represents a major event for patients
      undergoing adult spinal deformity (ASD) surgery. Previous reports suggest that
      ASD surgery has minimal or no impact on health-related-quality of life (HRQOL)
      outcomes. PURPOSE: The present study aims to investigate the impact of early
      reoperations within the first year on HRQOL and on the likelihood of reaching the
      minimally clinically important difference (MCID) after ASD surgery. DESIGN: This
      is a retrospective analysis of prospectively collected data from consecutive
      surgically treated adult deformity surgery patients included in a multicenter,
      international database. PATIENT SAMPLE: The present study included 280 patients
      from a multicenter international prospective database. OUTCOME MEASURE: Oswestry
      Disability Index (ODI), Short Form-36 (SF-36), Scoliosis Research Society-22 (SRS
      22), MCID were evaluated in this work. METHODS: Consecutive surgical patients
      with ASD recruited prospectively in six different centers from four countries
      with a minimum 2-year follow-up were stratified into two groups: R (revision
      surgery within the first year) and NR (no revision). Health-related-quality of
      life (ODI, SF-36, SRS-22) was assessed and compared at 6-month, 1-year, and 2
      year follow-up stages. Statistical analysis included chi-square tests, Student t
      tests, and linear mixed models. RESULTS: Forty-three patients (R Group) received
      46 revision surgeries. Nineteen patients (41.3%) had implant-related
      complications, 9 patients (19.6%) had deep surgical site infections, 9 patients
      (19.6%) had proximal junctional kyphosis, 3 patients (6.5%) had hematoma, and 6
      patients (13%) had other complications. Baseline characteristics differed between
      groups. At 6 months, all HRQOL scores improved in both groups, except in the SF
      36 Mental Component Summary and SRS-22 mental health domain in the R Group. At 1
      year, ODI and SRS-22 improvement was significantly greater in the NR Group,
      exceeding the reported MCID. At the 2-year follow-up, ODI, SRS-22, SF-36 MCS, and
      SF-36 PCS improvement was similar in both groups. However, postoperative change
      was only above the MCID for SF-36 PCS, ODI, and SRS-22 in the NR Group.
      CONCLUSIONS: Early unanticipated revision surgery has a negative impact on mental
      health at 6 months and reduces the chances of reaching an MCID improvement in SRS
      22, SF-36 PCS, and ODI at the 2-year follow-up.

PMID- 29037975
TI  - Modular cell-based platform for high throughput identification of compounds that
      inhibit a viral interferon antagonist of choice.
AB  - Viral interferon (IFN) antagonists are a diverse class of viral proteins that
      counteract the host IFN response, which is important for controlling viral
      infections. Viral IFN antagonists are often multifunctional proteins that perform
      vital roles in virus replication beyond IFN antagonism. The critical importance
      of viral IFN antagonists is highlighted by the fact that almost all viruses
      encode one of these proteins. Inhibition of viral IFN antagonists has the
      potential to exert pleiotropic antiviral effects and thus this important protein
      class represents a diverse plethora of novel therapeutic targets. To exploit
      this, we have successfully developed and executed a novel modular cell-based
      platform that facilitates the safe and rapid screening for inhibitors of a viral
      IFN antagonist of choice. The platform is based on two reporter cell-lines that
      provide a simple method to detect activation of IFN induction or signaling via an
      eGFP gene placed under the control of the IFNbeta or an ISRE-containing promoter,
      respectively. Expression of a target IFN antagonist in the appropriate reporter
      cell-line will block the IFN response and hence eGFP expression. We hypothesized
      that addition of a compound that inhibits IFN antagonist function will release
      the block imposed on the IFN response and hence restore eGFP expression,
      providing a measurable parameter for high throughput screening (HTS). We
      demonstrate assay proof-of-concept by (i) exploiting hepatitis C virus (HCV)
      protease inhibitors to inhibit NS3-4A's capacity to block IFN induction and (ii)
      successfully executing two HTS targeting viral IFN antagonists that block IFN
      signaling; NS2 and IE1 from human respiratory syncytial virus (RSV) and
      cytomegalovirus (CMV) respectively, two clinically important viruses for which
      vaccine development has thus far been unsuccessful and new antivirals are
      required. Both screens performed robustly and Z' Factor scores of >0.6 were
      achieved. We identified (i) four hit compounds that specifically inhibit RSV
      NS2's ability to block IFN signaling by mediating STAT2 degradation and exhibit
      modest antiviral activity and (ii) two hit compounds that interfere with IE1
      transcription and significantly impair CMV replication. Overall, we demonstrate
      assay proof-of-concept as we target viral IFN antagonists from unrelated viruses
      and demonstrate its suitability for HTS.

PMID- 29037976
TI  - Characterization of a dengue NS4B inhibitor originating from an HCV small
      molecule library.
AB  - Dengue is the most important mosquito-transmitted viral disease and a major
      global health concern. Over the last decade, dengue virus (DENV) drug discovery
      and development has intensified, however, this has not resulted in approved DENV
      specific antiviral treatments yet. DENV and hepatitis C virus (HCV) belong to the
      same Flaviviridae family and, in contrast to DENV, antiviral treatments for HCV
      have been licensed. Therefore, applying the knowledge gained on anti-HCV drugs
      may foster the discovery and development of dengue antiviral drugs. Here, we
      screened a library of compounds with established anti-HCV activity in a DENV-2
      sub-genomic replicon inhibition assay and selected compounds with single-digit
      micromolar activity. These compounds were advanced into a hit-to-lead medicinal
      chemistry program resulting in lead compound JNJ-1A, which inhibited the DENV-2
      sub-genomic replicon at 0.7 MUM, in the absence of cytotoxicity. In addition, JNJ
      1A showed equipotent antiviral activity against DENV serotypes 1, 2, and 4. In
      vitro resistance selection experiments with JNJ-1A induced mutation T108I in non
      structural protein 4B (NS4B), pointing towards a mechanism of action linked to
      this protein. Collectively, we described the discovery and characterization of a
      novel DENV inhibitor potentially targeting NS4B.

PMID- 29037977
TI  - Toxocariasis in humans in Africa - A systematic review.
AB  - BACKGROUND: Toxocariasis is a globally distributed zoonosis. The most important
      definitive hosts are dogs, whereas humans serve as paratenic hosts. Transmission
      to humans occurs by accidental ingestion of eggs, e.g. by consumption of
      contaminated fruits or vegetables. Although exposure to Toxocara is usually
      considered as relatively benign, it is implicated in a range of neurological,
      ophthalmologic and other organ-specific conditions, some of them with grave
      consequences. This review provides an overview on the epidemiology, presentation
      and risk factors of exposure to Toxocara in Africa. METHODS: A systematic search
      was performed for studies published after January 1st, 1990, in English, French,
      Portuguese, Spanish, Dutch or German. The review was prepared according to PRISMA
      guidelines. Studies on toxocariasis in human populations and contamination in
      human environments were included. RESULTS: Sixty-five papers were included.
      Antibodies against Toxocara spp. in humans were found to be very common across
      Africa. Severe manifestations have been reported mainly from North Africa.
      Environmental contamination including soil, vegetables and fruits sold on markets
      was demonstrated in various locations in Africa. CONCLUSIONS: Exposure to
      Toxocara is prevalent across the African continent. However, the complication
      frequency, the impact of the condition on the individual and the public health
      relevance of this zoonosis, and the economic impact have never been
      systematically evaluated.

PMID- 29037978
TI  - Expected immunizations and health protection for Hajj and Umrah 2018 -An
      overview.
AB  - BACKGROUND: The annual Hajj and Umrah are one of the largest recurring religious
      mass gatherings across the globe drawing pilgrims from more than 185 countries.
      The living circumstances and activities of the pilgrims may create an environment
      for the occurrence and spread of communicable diseases. Each year, the Health
      authority of the Kingdom of Saudi Arabia, in coordination with international
      health authorities, updates health requirements for pilgrims. The Hajj for 2017
      took place from August 24 to September 5, 2017. Here, we review the expected
      obligations for immunizations for the 2018 Hajj and Umrah. RESULTS: The Hajj and
      Umrah vaccine requirements include mandatory vaccinations against yellow fever,
      quadrivalent meningococcal polysaccharide (every 3 years) or conjugated (every 5
      years) vaccines and poliomyelitis vaccine. Influenza vaccine utilizing the 2016
      (Southern Hemisphere vaccine to all pilgrims) was recommended but was not
      obligatory for pilgrims. Ciprofloxacin is required for individuals >12 years
      excluding pregnant women as chemoprophylaxis to be given at the port of entry for
      Pilgrims coming from the meningitis belt. With the ongoing outbreaks of measles
      in Europe, it is recommended that all pilgrims have an updated immunization
      against vaccine-preventable diseases (diphtheria, tetanus, pertussis, polio,
      measles and mumps). CONCLUSION: The mandatory vaccines remain the same with
      continued vigilance for the development of any new or emerging infectious
      diseases. Continuing surveillance for Zika virus, cholera and MERS-CoV are
      ongoing.

PMID- 29037970
TI  - Early years postgraduate surgical training programmes in the UK are failing to
      meet national quality standards: An analysis from the ASiT/BOTA Lost Tribe
      prospective cohort study of 2,569 surgical trainees.
AB  - INTRODUCTION: This study aimed to assess training of Senior House Officer-grade
      equivalent doctors in postgraduate surgical training or service (SHO-DIPST) in
      surgical specialties across the United Kingdom (UK), against nationally agreed
      Joint Committee on Surgical Training Quality Indicators (JCST QIs). Specific
      recommendations are made, with a view to improving quality of training, workforce
      retention and recruitment to Higher Surgical Training. METHOD: Prospective,
      observational, multicentre study conducted by the Association of Surgeons in
      Training, using the UK National Research Collaborative model. Any centres in the
      UK providing acute surgical services were eligible. SHO-DIPST with a permanent
      contract, on out-of-hours 'on-call rota' were included across four, one-week data
      capture periods (September to October 2016, February to March 2017). Adherence to
      five quality indicators was reported using descriptive statistics. P-values were
      calculated using Student's t-test for continuous data, with a 5% level of
      significance. RESULTS: 2569 SHO-DIPST were included from all ten surgical
      specialties in 141 NHS trusts across all 16 Local Education and Training Boards
      in the UK. 960 SHO-DIPST were in registered 'training' posts (37.3%). The median
      number of SHO-DIPST per rota was 7.0 (IQR 5.0-9.0). Adherence to the five
      included JCST QIs ranged from 6.0 to 53.1%. Only four SHO-DIPST posts across the
      study population met all five JCST QIs (0.3%). The total number of training
      sessions was higher for those in registered training posts (p < 0.001), with
      significant specialty and regional variation. CONCLUSIONS: Only four early years
      postgraduate surgical training posts in the UK meet nationally approved minimum
      quality standards. Specific recommendations are made to improve training in this
      cohort and to bolster recruitment and retention into Higher Surgical Training.

PMID- 29037979
TI  - Maritime illness and death reporting and public health response, United States,
      2010-2014.
AB  - BACKGROUND: Deaths and certain illnesses onboard ships arriving at US ports are
      required to be reported to the US Centers for Disease Control and Prevention
      (CDC), and notifications of certain illnesses are requested. METHODS: We
      performed a descriptive analysis of required maritime illness and death reports
      of presumptive diagnoses and requested notifications to CDC's Division of Global
      Migration and Quarantine, which manages CDC's Quarantine Stations, from January
      2010 to December 2014. RESULTS: CDC Quarantine Stations received 2891 individual
      maritime case reports: 76.8% (2221/2891) illness reports, and 23.2% (670/2891)
      death reports. The most frequent individual illness reported was varicella
      (35.9%, 797/2221) and the most frequently reported causes of death were
      cardiovascular- or pulmonary-related conditions (79.6%, 533/670). There were 7695
      cases of influenza-like illness received within aggregate notifications. CDC
      coordinated 63 contact investigations with partners to identify 972 contacts;
      88.0% (855/972) were notified. There was documentation of 6.5% (19/293) receiving
      post-exposure prophylaxis. Three pertussis contacts were identified as secondary
      cases; and one tuberculosis contact was diagnosed with active tuberculosis.
      CONCLUSION: These data provide a picture of US maritime illness and death
      reporting and response. Varicella reports are the most frequent individual
      disease reports received. Contact investigations identified few cases of disease
      transmission.

PMID- 29037980
TI  - Improved stability of live attenuated vaccine gdhA derivative Pasteurella
      multocida B:2 by freeze drying method for use as animal vaccine.
AB  - The efficacy of attenuated strain of gdhA derivative Pasteurella multocida B:2
      mutant as a live vaccine to control haemorrhagic septicaemia (HS) disease in
      cattle and buffaloes has been demonstrated. In order to use P. multocida B:2
      mutant as a commercial product, it is essential to optimise its formulation for
      high viability and stability of the live cells. The effectiveness of freeze
      drying process using different protective agent formulations for improving cells
      viability was explored. Sugar and nitrogen compounds were used as protective
      agents in freeze-drying and the capability of these compounds in maintaining the
      viability of mutant P. multocida B:2 during subsequent storage was investigated.
      A complete loss in viability of freeze-dried mutant P. multocida B:2 was monthly
      observed until 6-12 months of storage at -30  degrees C, 4  degrees C and 27 
      degrees C when nitrogen compound or no protective agent was added. Trehalose and
      sucrose showed significantly high survival rate of 93-95% immediately after
      freeze-drying and the viability was retained during the subsequent storage at -30
      degrees C and 4  degrees C. A smooth cell surface without any cell-wall damage
      was observed for the cells formulated with trehalose under scanning electron
      micrograph. This study presented a freeze-drying process generating a dried live
      attenuated vaccine formulation with high stability for commercial applications.

PMID- 29037981
TI  - Effect of incubation temperature after devitrification on quality parameters in
      human sperm cells.
AB  - Sperm cryopreservation is common in assisted reproduction laboratories, providing
      a therapeutic option for several clinical conditions. This process has been
      optimized; however, the effect of post-thaw incubation temperature has been
      poorly studied. This work analyzed the effect of incubation temperature after
      devitrification on human sperm quality. Spermatozoa from normozoospermic donors
      were cryopreserved by vitrification. After devitrification, the spermatozoa were
      separated into two aliquots: (i) incubated at room temperature (RT, 22-25 
      degrees C) and (ii) incubated at 37  degrees C. Reactive oxygen species (ROS),
      viability, mitochondrial membrane potential (DeltaPsiM), phosphatidylserine
      externalization and motility were analyzed immediately after devitrification
      (control) and after 2, 4 and 6 h. Spermatozoa incubated at RT showed a conserved
      viability and DeltaPsiM compared to the control, while the incubation at 37 
      degrees C promoted a decrease in these parameters. The ROS levels were increased
      at both incubation conditions. The progressive motility was decreased in all
      experimental groups and the decrease was more pronounced under incubation at RT.
      No increase in phosphatidylserine externalization was observed. In conclusion,
      prior to use in assisted reproduction procedures, devitrified spermatozoa at RT
      conserve a better viability and DeltaPsiM than at 37  degrees C.

PMID- 29037982
TI  - Early effects of Epac depend on the fine-tuning of the sarcoplasmic reticulum
      Ca2+ handling in cardiomyocytes.
AB  - In cardiac muscle, signaling through cAMP governs many fundamental cellular
      functions, including contractility, relaxation and automatism. cAMP cascade leads
      to the activation of the classic protein kinase A but also to the stimulation of
      the recently discovered exchange protein directly activated by cAMP (Epac). The
      role of Epac in the regulation of intracellular Ca2+ homeostasis and
      contractility in cardiac myocytes is still matter of debate. In this study we
      showed that the selective Epac activator, 8-(4-chloro-phenylthio)-2'-O
      methyladenosine-3', 5'-cyclic monophosphate (8-CPT), produced a positive
      inotropic effect when adult rat cardiac myocytes were stabilized at low [Ca2+]o
      (0.5mM), no changes at 1mM [Ca2+]o and a negative inotropic effect when [Ca2+]o
      was increased to 1.8mM. These effects were associated to parallel variations in
      sarcoplasmic reticulum (SR) Ca2+ content. At all [Ca2+]o studied, 8-CPT induced
      an increase in Ca2+ spark frequency and enhanced CaMKII autophosphorylation and
      the CaMKII-dependent phosphorylation of SR proteins: phospholamban (PLN, at Thr17
      site) and ryanodine receptor (RyR2, at Ser2814 site). We used transgenic mice
      lacking PLN CaMKII phosphorylation site (PLN-DM) and knock-in mice with an
      inactivated CaMKII site S2814 on RyR2 (RyR2-S2814A) to investigate the
      involvement of these processes in the effects of Epac stimulation. In PLN-DM
      mice, 8-CPT failed to induce the positive inotropic effect at low [Ca2+]o and
      RyR2-S2814A mice showed no propensity to arrhythmic events when compared to wild
      type mice myocytes. We conclude that stimulation of Epac proteins could have
      either beneficial or deleterious effects depending on the steady-state Ca2+
      levels at which the myocyte is functioning, favoring the prevailing mechanism of
      SR Ca2+ handling (uptake vs. leak) in the different situations.

PMID- 29037985
TI  - Adjuvant zoledronic acid to treat breast cancer: not for all.

PMID- 29037984
TI  - Effect of MAF amplification on treatment outcomes with adjuvant zoledronic acid
      in early breast cancer: a secondary analysis of the international, open-label,
      randomised, controlled, phase 3 AZURE (BIG 01/04) trial.
AB  - BACKGROUND: Adjuvant use of bisphosphonates can reduce the incidence of bone
      metastases in early breast cancer. Recurrence and survival seem to be improved
      only in postmenopausal patients, but the underlying mechanisms remain unclear. We
      investigated whether MAF amplification (a biomarker for bone metastasis) in
      primary tumours could predict the treatment outcomes of adjuvant zoledronic acid.
      METHODS: The study population included patients enrolled in the international,
      open-label, randomised, controlled, phase 3 AZURE trial at eligible UK sites who
      had stage II or III breast cancer and who gave consent for use of their primary
      tumour samples. Patients were randomly assigned (1:1) to receive standard
      adjuvant systemic therapy alone (control group) or with zoledronic acid every 3-4
      weeks for six doses, then every 3-6 months until the end of 5 years. Minimisation
      took into account the number of involved axillary lymph nodes, clinical tumour
      stage, oestrogen-receptor status, type and timing of systemic therapy, menopausal
      status, statin use, and treating centre. The primary endpoint was disease-free
      survival; the secondary endpoint, invasive-disease-free survival, was the primary
      disease endpoint for the analysis in this report. MAF amplification was assessed
      by fluorescence in-situ hybridisation of two cores of breast tumour tissue in a
      microarray, done in a central laboratory by technicians unaware of treatment
      assignment. We used multivariate analyses to assess disease outcomes by intention
      to treat. We also assessed interactions between MAF-positive status and
      menopausal status on efficacy of zoledronic acid. The AZURE trial is registered
      with the International Standard Randomised Controlled Trial Registry, number
      ISRCTN79831382. FINDINGS: 1739 AZURE patients contributed primary tumour samples,
      of whom 865 (50%) had two assessable cores (445 in the control groups and 420 in
      the zoledronic acid group). 184 (21%) tumours were MAF positive (85 in the
      control groups and 99 in the zoledronic acid group) and the remaining tumours
      were MAF negative. At a median follow-up of 84.6 months (IQR 72.0-95.8), MAF
      status was not prognostic for invasive-disease-free survival in the control group
      (MAF-positive vs MAF-negative: hazard ratio [HR] 0.92, 95% CI 0.59-1.41), but was
      in the zoledronic acid group (0.52, 0.36-0.75). In patients with MAF-negative
      tumours, zoledronic acid was associated with higher invasive-disease-free
      survival than was control treatment (HR 0.74, 95% CI 0.56-0.98), but not in
      patients who had MAF-positive tumours. Additionally, among 121 patients not
      postmenopausal at randomisation with MAF-positive tumours, zoledronic acid was
      associated with lower invasive-disease-free survival (HR 2.47, 95% CI 1.23-4.97)
      and overall survival (2.27, 95% CI 1.04-4.93) than control treatment.
      INTERPRETATION: MAF status can predict likelihood of benefit from adjuvant
      zoledronic acid and merits further investigation as a potential companion
      diagnostic. FUNDING: Novartis Global and Inbiomotion.

PMID- 29037983
TI  - Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS
      8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast
      and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study.
AB  - BACKGROUND: Antibody-drug conjugates have emerged as a powerful strategy in
      cancer therapy and combine the ability of monoclonal antibodies to specifically
      target tumour cells with the highly potent killing activity of drugs with
      payloads too toxic for systemic administration. Trastuzumab deruxtecan (also
      known as DS-8201) is an antibody-drug conjugate comprised of a humanised antibody
      against HER2, a novel enzyme-cleavable linker, and a topoisomerase I inhibitor
      payload. We assessed its safety and tolerability in patients with advanced breast
      and gastric or gastro-oesophageal tumours. METHODS: This was an open-label, dose
      escalation phase 1 trial done at two study sites in Japan. Eligible patients were
      at least 20 years old with breast or gastric or gastro-oesophageal carcinomas
      refractory to standard therapy regardless of HER2 status. Participants received
      initial intravenous doses of trastuzumab deruxtecan from 0.8 to 8.0 mg/kg and
      dose-limiting toxicities were assessed over a 21-day cycle; thereafter, dose
      reductions were implemented as needed and patients were treated once every 3
      weeks until they had unacceptable toxic effects or their disease progressed.
      Primary endpoints included identification of safety and the maximum tolerated
      dose or recommended phase 2 dosing and were analysed in all participants who
      received at least one dose of study drug. The dose-escalation study is the first
      part of a two-part study with the second dose-expansion part ongoing and
      enrolling patients as of July 8, 2017, in Japan and the USA. This trial is
      registered at ClinicalTrials.gov, number NCT02564900. FINDINGS: Between Aug 28,
      2015, and Aug 26, 2016, 24 patients were enrolled and received trastuzumab
      deruxtecan (n=3 for each of 0.8, 1.6, 3.2, and 8.0 mg/kg doses; n=6 for each of
      5.4 and 6.4 mg/kg). Up to the study cutoff date of Feb 1, 2017, no dose-limiting
      toxic effects, substantial cardiovascular toxic effects, or deaths occurred. One
      patient was removed from the activity analysis because they had insufficient
      target lesions for analysis. The most common grade 3 adverse events were
      decreased lymphocyte (n=3) and decreased neutrophil count (n=2); and grade 4
      anaemia was reported by one patient. Three serious adverse events-febrile
      neutropenia, intestinal perforation, and cholangitis-were reported by one patient
      each. Overall, in 23 evaluable patients, including six patients with low HER2
      expressing tumours, ten patients achieved an objective response (43%, 95% CI 23.2
      65.5). Disease control was achieved in 21 (91%; 95% CI 72.0-98.9) of 23 patients.
      Median follow-up time was 6.7 months (IQR 4.4-10.2), with nine (90%) of ten
      responses seen at doses of 5.4 mg/kg or greater. INTERPRETATION: The maximum
      tolerated dose of trastuzumab deruxtecan was not reached. In this small, heavily
      pretreated study population, trastuzumab deruxtecan showed antitumour activity,
      even in low HER2-expressing tumours. Based on safety and activity, the most
      likely recommended phase 2 dosing is 5.4 or 6.4 mg/kg. FUNDING: Daiichi Sankyo
      Co, Ltd.

PMID- 29037986
TI  - Antibody-drug conjugates: can the payload improve activity in HER2 expressing
      cancers?

PMID- 29037987
TI  - RNA methylation regulates hematopoietic stem and progenitor cell development.

PMID- 29037988
TI  - Efficient genetic manipulation in the developing brain of tree shrew using in
      utero electroporation and virus infection.

PMID- 29037989
TI  - Genome wide abnormal DNA methylome of human blastocyst in assisted reproductive
      technology.
AB  - Proper reprogramming of parental DNA methylomes is essential for mammalian
      embryonic development. However, it is unknown whether abnormal methylome
      reprogramming occurs and is associated with the failure of embryonic development.
      Here we analyzed the DNA methylomes of 57 blastocysts and 29 trophectoderm
      samples with different morphological grades during assisted reproductive
      technology (ART) practices. Our data reveal that the global methylation levels of
      high-quality blastocysts are similar (0.30 +/- 0.02, mean +/- SD), while the
      methylation levels of low-quality blastocysts are divergent and away from those
      of high-quality blastocysts. The proportion of blastocysts with a methylation
      level falling within the range of 0.30 +/- 0.02 in different grades correlates
      with the live birth rate for that grade. Moreover, abnormal methylated regions
      are associated with the failure of embryonic development. Furthermore, we can use
      the methylation data of cells biopsied from trophectoderm to predict the
      blastocyst methylation level as well as to detect the aneuploidy of the
      blastocysts. Our data indicate that global abnormal methylome reprogramming often
      occurs in human embryos, and suggest that DNA methylome is a potential biomarker
      in blastocyst selection in ART.

PMID- 29037990
TI  - Roles for the VCP co-factors Npl4 and Ufd1 in neuronal function in Drosophila
      melanogaster.
AB  - The VCP-Ufd1-Npl4 complex regulates proteasomal processing within cells by
      delivering ubiquitinated proteins to the proteasome for degradation. Mutations in
      VCP are associated with two neurodegenerative diseases, amyotrophic lateral
      sclerosis (ALS) and inclusion body myopathy with Paget's disease of the bone and
      frontotemporal dementia (IBMPFD), and extensive study has revealed crucial
      functions of VCP within neurons. By contrast, little is known about the functions
      of Npl4 or Ufd1 in vivo. Using neuronal-specific knockdown of Npl4 or Ufd1 in
      Drosophila melanogaster, we infer that Npl4 contributes to microtubule
      organization within developing motor neurons. Moreover, Npl4 RNAi flies present
      with neurodegenerative phenotypes including progressive locomotor deficits,
      reduced lifespan and increased accumulation of TAR DNA-binding protein-43 homolog
      (TBPH). Knockdown, but not overexpression, of TBPH also exacerbates Npl4 RNAi
      associated adult-onset neurodegenerative phenotypes. In contrast, we find that
      neuronal knockdown of Ufd1 has little effect on neuromuscular junction (NMJ)
      organization, TBPH accumulation or adult behaviour. These findings suggest the
      differing neuronal functions of Npl4 and Ufd1 in vivo.

PMID- 29037991
TI  - Vegfa signaling regulates diverse artery/vein formation in vertebrate
      vasculatures.
AB  - Vascular endothelial growth factor A (Vegfa) signaling regulates vascular
      development during embryogenesis and organ formation. However, the signaling
      mechanisms that govern the formation of various arteries/veins in various tissues
      are incompletely understood. In this study, we utilized transcription activator
      like effector nuclease (TALEN) to generate zebrafish vegfaa mutants. vegfaa-/-
      embryos are embryonic lethal, and display a complete loss of the dorsal aorta
      (DA) and expansion of the cardinal vein. Activation of Vegfa signaling expands
      the arterial cell population at the expense of venous cells during vasculogenesis
      of the axial vessels in the trunk. Vegfa signaling regulates endothelial cell
      (EC) proliferation after arterial-venous specification. Vegfa deficiency and
      overexpression inhibit the formation of tip cell filopodia and interfere with the
      pathfinding of intersegmental vessels (ISVs). In the head vasculature, vegfaa-/-
      causes loss of a pair of mesencephalic veins (MsVs) and central arteries (CtAs),
      both of which usually develop via sprouting angiogenesis. Our results indicate
      that Vegfa signaling induces the formation of the DA at the expense of the
      cardinal vein during the trunk vasculogenesis, and that Vegfa is required for the
      angiogenic formation of MsVs and CtAs in the brain. These findings suggest that
      Vegfa signaling governs the formation of diverse arteries/veins by distinct
      cellular mechanisms in vertebrate vasculatures.

PMID- 29037992
TI  - Autophagy-related protein ATG5 regulates histone H2B mono-ubiquitylation by
      translational control of RNF20.

PMID- 29037993
TI  - Omalizumab response in patients with chronic idiopathic urticaria: Insights from
      the XTEND-CIU study.

PMID- 29037994
TI  - Ethical challenges with treating nonadherent patients in a group practice
      setting.

PMID- 29037996
TI  - Synthesis, anti-cancer screening and tyrosyl-DNA phosphodiesterase 1 (Tdp1)
      inhibition activity of novel piperidinyl sulfamides.
AB  - Novel piperidinyl-based sulfamide derivatives were designed and synthesized
      through various synthetic routes. Anticancer activities of these sulfamides were
      evaluated by phenotypic screening on National Cancer Institute's 60 human tumor
      cell lines (NCI-60). Preliminary screening at 10MUM concentration showed that
      piperidinyl sulfamide aminoester 26 (NSC 749204) was sensitive to most of the
      cell lines in the panel. Further dose-response studies showed that 26 was highly
      selective for inhibition of colon cancer cell lines with minimum GI50=1.88MUM for
      COLO-205 and maximum GI50=11.1MUM for SW-620 cells. These newly synthesized
      sulfamides were also screening for their Tdp1 inhibition activity. Compound 18
      (NSC 750706) showed significant inhibition of Tdp1 with IC50=23.7MUM. Molecular
      docking studies showed that 18 bind to Tdp1 in its binding pocket similar to a
      known Tdp1 inhibitor.

PMID- 29037995
TI  - Preclinical pharmacokinetic profiling of IQG-607, a potential oral metallodrug to
      treat tuberculosis.
AB  - IQG-607 is an analog of isoniazid with anti-tuberculosis activity. This work
      describes the development and validation of an HPLC method to quantify
      pentacyano(isoniazid)ferrate(II) compound (IQG-607) and the pharmacokinetic
      studies of this compound in mice. The method showed linearity in the 0.5-50MUg/mL
      concentration range (r=0.9992). Intra- and inter-day precision was <5%, and the
      recovery ranged from 92.07 to 107.68%. IQG-607 was stable in plasma for at least
      30days at -80 degrees C and, after plasma processing, for 4h in the auto-sampler
      maintained on ice (recovery >85%). The applicability of the method for
      pharmacokinetic studies was determined after intravenous (i.v.) and oral (fasted
      and fed conditions) administration to mice. IQG-607 levels in plasma were
      quantified at time points for up to 2.5h. A short half-life (t1/2) (1.14h), a
      high clearance (CL) (3.89L/h/kg), a moderate volume of distribution at steady
      state (Vdss) of 1.22L/kg, were observed after i.v. (50mg/kg) administration.
      Similar results were obtained for oral administration (250mg/kg) under fasted and
      fed conditions. The oral bioavailability (F), approximately 4%, was not altered
      by feeding. Plasma protein binding was 88.87+/-0.9%. The results described here
      provide novel insights into a pivotal criterion to warrant further efforts to be
      pursued towards attempts to translate this chemical compound into a
      chemotherapeutic agent to treat TB.

PMID- 29037998
TI  - Identification and analysis of the genetic causes in nine unrelated probands with
      syndromic craniosynostosis.
AB  - Syndromic craniosynostosis is a group of multiple conditions with high
      heterogeneity, and many rare syndromes still remain to be characterized. To
      identify and analyze causative genetic variants in nine unrelated probands mainly
      manifested as syndromic craniosynostosis, we reviewed the relevant medical
      information of the patients and performed the whole exome sequencing, further
      verified with Sanger sequencing and parental background. Bioinformatics analysis
      was used to evaluate the potential deleterious or benign effect of each genetic
      variant through evolutionary conservation alignment, multi-lines of computer
      predication and the allele frequency in population dataset (control and patient).
      The Standards and guidelines from American College of Medical Genetics and
      Genomics was used to classify and interpret the pathogenicity for each genetic
      variant. All the nine probands were found to carry the possibly causative
      variants, among which three variants including two missense mutations (c.3385C>T
      in IFT122 gene, c.3581A>G in SMC1A gene) and a frameshift mutation (c.434dupA in
      TWIST1 gene) have never been reported in patients before. We suggested Cornelia
      de Lange syndrome caused by SMC1A variant is a neglected syndromic
      craniosynostosis. Our study not only expanded genotypic and phenotypic spectrum
      of the rare syndromes, but also confirmed that there existed an underlying
      genetic mechanism. We emphasized that deliberate selection of both the potential
      candidates and comprehensive detection methods for genetic analysis is important
      to increase the genetic diagnosis yield of syndromic craninosynostosis.

PMID- 29037997
TI  - The ERAP gene is associated with HCV chronic infection in a Chinese Han
      population.
AB  - Endoplasmic reticulum aminopeptidases (ERAPs), ERAP1 and ERAP2, are critical
      components in the antigen-presentation system and are specialized to produce
      optimal-sized peptides for HLA I binding. ERAP gene polymorphisms have been
      correlated with HLA-associated diseases. To investigate the association between
      ERAP gene polymorphisms and HCV chronic infection, a TaqMan assay was used to
      genotype 4 SNPs (rs27044, rs30187, rs26618 and rs26653) in ERAP1 and 2 SNPs
      (rs2248374 and rs2549782) in ERAP2 genes in 376 Chinese Han HCV chronic
      infections and 324 healthy Chinese Han controls. The allelic distribution of
      rs26618 in the ERAP1 gene and rs2248374 in ERAP2 gene were both significantly
      different in case and control groups. The C-allele of rs26618 had an increased
      HCV chronicity risk compared with the T-allele (P=.025, OR=1.318, 95%CI: 1.035
      1.677), and the same effect was found in A-allele of rs2248374 compared with G
      allele (P=0.046, OR=1.244, 95%CI: 1.004-1.540). There were notable differences in
      the genotype distribution in analysis using the dominant genetic model in rs26618
      (CC+CT vs. TT; P=0.007, OR=1.473, 95%CI: 1.091-1.989) and recessive genetic model
      in rs2248374 (AA vs. AG+GG; P=0.003, OR=1.548, 95%CI: 1.026-2.335). In addition,
      rs26618 and rs2248374-genotype combination played noteable effects on the
      clinical parameters. These results indicated that the ERAP gene may play a
      critical role in HCV chronicity in this Chinese Han population.

PMID- 29037999
TI  - Protective effect of silk fibroin in burn injury in rat model.
AB  - Activation of pro-inflamatuar pathways play major role in formation of major
      complications as a result of burns. This study was planned to investigate the
      protective effect of Silk Fibroin in lung injury caused by burn in the
      experimental rat model. After rinsing the skin of rats under ether anesthesia,
      the exposed back region, covers 30% of the total body, was kept in the 90 degrees
      C water bath for 10s. The control rats were kept in the 25 degrees C water bath
      for 10s. Immediately after burning process, silk fibroin was administered orally
      at a dose of 600mg/kg. After 24h following burning from all groups the levels of
      TNF-alpha, IL-1beta in blood samples and the MDA, GSH and the activity of MPO
      were determined from taken lung tissues. Moreover, the expression of Bcl-2/Bax,
      Caspase-3 and Caspase-9 were determined. Significant increase in TNF-alpha, IL
      1beta, Casp-3 and Casp-9 levels were observed in the Silk Fibroin-treated burn
      group (p<0.05) whereas for ratio of Bcl-2/Bax, a significant reduction was
      observed compared to control group (p<0.05). Increased levels of TNF-alpha, IL
      1beta, Caspase-3 and Caspase-9 in Silk Fibroin-treated burn groups were found to
      be reversed. Silk fibroin can be an effective biomaterial in diminishing burn
      injury in tissue and apoptosis.

PMID- 29038000
TI  - Epigenetic regulation of miR-200 as the potential strategy for the therapy
      against triple-negative breast cancer.
AB  - MicroRNAs (miRNAs) are a class of small, non-coding RNAs that are involved in the
      regulation of gene expression at the post-transcriptional level. MicroRNAs play
      an important role in cancer cell proliferation, survival and apoptosis.
      Epigenetic modifiers regulate the microRNA expression. Among the epigenetic
      players, histone deacetylases (HDACs) function as the key regulators of microRNA
      expression. Epigenetic machineries such as DNA and histone modifying enzymes and
      various microRNAs have been identified as the important contributors in cancer
      initiation and progression. Recent studies have shown that developing innovative
      microRNA-targeting therapies might improve the human health, specifically against
      the disease areas of high unmet medical need. Thus microRNA based therapeutics
      are gaining importance for anti-cancer therapy. Studies on Triple negative breast
      cancer (TNBC) have revealed the early relapse and poor overall survival of
      patients which needs immediate therapeutic attention. In this report, we focus
      the effect of HDAC inhibitors on TNBC cell proliferation, regulation of microRNA
      gene expression by a series of HDAC genes, chromatin epigenetics, epigenetic
      remodelling at miR-200 promoter and its modulation by various HDACs. We also
      discuss the need for identifying novel HDAC inhibitors for modulation of miR-200
      in triple negative breast cancer.

PMID- 29038001
TI  - G0S2a1 (G0/G1 switch gene 2a1) is downregulated by TNF-alpha in grass carp
      (Ctenopharyngodon idellus) hepatocytes through PPARalpha inhibition.
AB  - G0/G1 switch gene 2 plays an important role in the regulation of lipolysis in
      mammals, but little is known about its gene (G0S2) structure and function in
      fish. In the present study, two genes, G0S2a and G0S2b were isolated and
      characterized from grass carp Ctenopharyngodon idella, which encode peptides of
      111 and 84 amino acids, respectively. Moreover, alternative multiple exon usage
      resulted in a significant variation in the 5'-region of G0S2a transcripts
      yielding two isoforms (G0S2a1 and G0S2a2). Phylogenetic and synteny analyses
      indicated that G0S2a and G0S2b could have originated from the teleost-specific
      genome duplication event. Analysis of the exon-intron structures clarified that
      G0S2a contained an extra intron compared with G0S2b. G0S2a1, G0S2a2 and G0S2b
      mRNAs were highly expressed in adipose tissue and liver. G0S2a was localized to
      the cytoplasm and nucleus, while G0S2b was mainly localized in cytoplasm,
      suggesting that G0S2a and G0S2b may have different functions in grass carp.
      PPARalpha agonist caused an increase in G0S2a1 and G0S2b expression, revealing
      that they are subject to transcriptional control by PPARalpha-mediated signals.
      TNF-alpha treatment decreased G0S2a1 and G0S2a2 transcripts that paralleled TNF
      alpha downregulation of PPARalpha; however, only the effects of TNF-alpha on
      G0S2a1 were attenuated by treatment with PPARalpha agonist. Our findings identify
      G0S2a, not G0S2b, as a target gene for TNF-alpha and reveal that TNF-alpha
      suppresses G0S2a1 gene expression through a PPARalpha-dependent pathway in grass
      carp hepatocytes.

PMID- 29038002
TI  - Comparison of different nucleic acid preparation methods to improve specific HIV
      1 RNA isolation for viral load testing on dried blood spots.
AB  - In resource-limited countries (RLCs), WHO recommends HIV viral load (VL) on dried
      blood spots (DBS) for antiretroviral therapy (ART) monitoring of patients living
      in non-urban settings where plasma VL is not available. In order to reduce the
      impact of proviral DNA interference, leading to false positive results in samples
      with low plasma VL, we compared three different nucleic acid preparation methods
      with the NucliSens (Biomerieux) extraction, known for its high recovery of
      nucleic acids on DBS. Paired plasma-DBS samples (n=151) with predominantly low
      plasma VL (<=10,000 copies/ml; 74%) were used. At the threshold of 1,000
      copies/ml on DBS, 51% and 10% were misclassified as false positives or false
      negatives, respectively with NucliSens, versus 41% and 20% with m2000sp (Abbott),
      described as more specific for RNA recovery. DNase treatments of nucleic acid
      extracts and free virus elution (FVE) protocol before nucleic acid extraction,
      reduced the proportion of false positives to 0% and 19%, but increased the
      proportion of false negatives to 40% and 73%. More efforts are thus still needed
      to improve performance of VL assays on DBS to monitor patients on ART in RLCs and
      allow timely switch to more costly second or third line ART regimes.

PMID- 29038003
TI  - Hemin supports the survival of photoreceptors injured by N-Methyl-N-nitrosourea:
      The contributory role of neuroglobin in photoreceptor degeneration.
AB  - Retina is a critical component of the central nerve system that is responsible
      for the conversion of light stimulus into electrical spikes. Retinitis pigmentosa
      (RP) comprises a heterogeneous group of inherited retinal dystrophies leading to
      blindness. We examined retinal neuroglobin (Ngb) expression in a
      pharmacologically induced RP animal model, the N-Methyl-N-nitrosourea (MNU)
      administered mice. The retinal Ngb expression in MNU administered mice attenuated
      following a time dependent manner, suggesting Ngb was involved in the
      photoreceptor degeneration. Conversely, the intravenous delivery of Hemin, a Ngb
      up-regulator, enhanced the Ngb expressions in the retinas of MNU administered
      mice. Optokinetic behavioral tests and Electroretinogram (ERG) examination
      suggested that the Hemin treatment could improve the visual function of MNU
      administered mice. The retinal morphology of the Hemin treated group was much
      more intact than the MNU group as evidenced by retinal sections and optical
      coherence tomography (OCT) examinations. Moreover, immunostaining experiments
      showed the cone photoreceptors in the MNU administered mice were also rescued by
      Hemin treatment. Furthermore, mechanism studies suggested the Hemin treatment not
      only alleviated the oxidative stress, but also rectified the apoptotic changes in
      the retinas of MNU administered mice. In conclusion, the intraperitoneally
      delivery of Hemin can enhance the Ngb expressions in the MNU administered
      retinas, thereby ameliorating the photoreceptor degeneration and associated
      visual impairments. These findings would shed light on the opportunity to develop
      Ngb into a therapeutic molecular against RP.

PMID- 29038004
TI  - Flavonoid-rich ethanol extract from the leaves of Diospyros kaki attenuates
      cognitive deficits, amyloid-beta production, oxidative stress, and
      neuroinflammation in APP/PS1 transgenic mice.
AB  - Amyloid-beta peptide (Abeta) initiates a cascade of pathological events,
      including activation of microglial cells, oxidative stress, and inflammation,
      leading to neuronal death and the typical pathological changes in Alzheimer's
      disease (AD). Flavonoids have been reported to exert neuroprotective activities,
      not only through their generally accepted antioxidant effects, but also through
      their ability to protect against neurotoxin-induced injury. Flavonoids reduce
      Abeta production, inhibit neuroinflammation, increase cerebrovascular function,
      and improve cognitive performance. Here, we analyzed the effects of a flavonoid
      rich ethanol extract from the leaves of Diospyros kaki (FLDK) in APP/PS1
      transgenic mice. We found that oral treatment with FLDK reversed learning and
      memory impairment, reduced Abeta burden and expression of beta-site amyloid
      precursor protein cleavage enzyme 1 (BACE1), and decreased microglial activation
      in senile plaques. FLDK restored antioxidant enzyme activities, as well as
      reduced the lipid peroxidation product, malondialdehyde, and inflammatory
      mediators. These results demonstrate that FLDK alleviates cognitive decline and
      reduces Abeta burden, microglial activation, oxidative stress, and inflammation
      responses. Thus, FLDK treatment may be a potential therapeutic strategy for
      preventing and treating AD, at least in part via its anti-oxidant and anti
      inflammatory biological activities and its effect on the Abeta producing enzyme
      BACE1.

PMID- 29038005
TI  - Prednisone alleviates demyelination through regulation of the NLRP3 inflammasome
      in a C57BL/6 mouse model of cuprizone-induced demyelination.
AB  - Myelin abnormalities, oligodendrocyte damage, and concomitant glia activation are
      common in demyelinating diseases of the central nervous system (CNS). Increasing
      evidence has demonstrated that the inflammatory response triggers demyelination
      and gliosis in demyelinating disorders. Numerous clinical interventions,
      including those used to treat multiple sclerosis (MS), have confirmed prednisone
      (PDN) as a powerful anti-inflammatory drug that reduces the inflammatory response
      and promotes tissue repair in multiple inflammation sites. However, the
      underlying mechanism of PDN in ameliorating myelin damage is not well understood.
      In our study, a cuprizone (CPZ)-induced demyelinated mouse model was used to
      explore the mechanism of the protection provided by PDN. Open-field tests showed
      that CPZ-treated mice exhibited significantly increased anxiety and decreased
      exploration. However, PDN improved emotional behavior, as evidenced by an
      increase in the total distance traveled, and central distance traveled as well as
      the mean amount of time spent in the central area. CPZ-induced demyelination was
      observed to be alleviated in PDN-treated mice based on luxol fast blue (LFB)
      staining and myelin basic protein (MBP) expression analyses. In addition, PDN
      reduced astrocyte and microglia activation in the corpus callosum. Furthermore,
      we demonstrated that PDN inhibited the Nod-like receptor pyrin domain containing
      3 (NLRP3) inflammasome signaling pathway and related inflammatory cytokines and
      chemokines, including TNF-alpha, CCL8, CXCL10 and CXCL16. PDN also reduced the
      serum corticosterone levels in the CPZ-treated mice. Taken together, these
      results suggest that inhibition of the NLRP3 signaling pathway may be a novel
      mechanism by which PDN exerts its protective actions in demyelinating diseases.

PMID- 29038006
TI  - Role of CA1 GABAA and GABAB receptors on learning deficit induced by D-AP5 in
      passive avoidance step-through task.
AB  - To investigate the interaction between hippocampal gamma-aminobutyric acid GABAA
      receptor (GABAAR) or GABAB receptor (GABABR) and N-methyl-D-aspartate receptor
      (NMDAR) in the acquisition of passive avoidance memory in rats, we used GABAA or
      GABAB agents, D-AP5 (as a NMDAR antagonist), and a combination of the mentioned
      drugs in a step-through task. All agents were microinjected into the intra-CA1
      regions at a volume of 1 ul/rat, prior to training. GABAAR agonist muscimol (0.2
      ug/rat), selective GABABR agonist baclofen (0.5 ug/rat) or NMDAR antagonist D-AP5
      (0.25 ug/rat) decreased step-through latency, indicating a memory retention
      impairment. Neither GABAAR antagonist bicuculline (0.0625-0.25 ug/rat) nor GABABR
      antagonist phaclofen (0.1-0.5 ug/rat) altered memory retrieval by itself.
      Moreover, the lower dose of muscimol (0.05 ug/rat) decreased D-AP5 (0.125 ug/rat)
      response on memory acquisition, but bicuculline did not alter the D-AP5 response.
      Furthermore, baclofen and phaclofen at the dose of 0.1 ug/rat potentiated D-AP5
      response at the doses of 0.0625 and 0.125 ug/rat, but abolished memory impairment
      induced by D-AP5 at the higher dose (0.25 ug/rat). The results suggest that the
      microinjection of GABAA and GABAB agents into the CA1 region differently affects
      memory acquisition deficit induced by D-AP5. The activation of GABAARs increased
      the impairment effect of D-AP5 on passive avoidance memory, but their blockade
      did not have an effect. Also, the activation or blockade of GABABRs induced a
      similar and dual effect.

PMID- 29038007
TI  - Baicalin and ginsenoside Rb1 promote the proliferation and differentiation of
      neural stem cells in Alzheimer's disease model rats.
AB  - BACKGROUND: This study aimed to explore the effects of ginsenoside Rb1 and
      baicalin on the proliferation and differentiation of neural stem cells (NSC) in
      Alzheimer's disease model rats. METHOD: The healthy Sprague Dawley male rats were
      randomly divided into 4 groups: control group, model group, ginsenoside Rb1 group
      and baicalin group. Besides, the animal model of dementia was induced by the
      injection of Abeta1-40. 2 weeks later, the rats in the baicalin and ginsenoside
      Rb1 groups were injected with baicalin and ginsenoside Rb1, respectively. The
      contents, expression sites of Nestin, GFAP and NSE and the percentage of viable
      cells were detected by immunohistochemistry. In addition, the expression levels
      of Nestin, GFAP and NSE in hippocampus of rats were detected by western-blot and
      metrology analysis was performed using quantity. RESULTS: Injection of Abeta1-40
      significantly reduced the number of neuronal cells (p < .05). In addition,
      compared with the control group, the percentages of positive cells of NSCs,
      astrocytes and neuronal were increased. Besides, compared with the model group,
      the percentage of positive neural cells was improved by ginsenoside Rb1 (p <
      .05), and the percentages of astrocytes and neuronal were increased by
      ginsenoside Rb1 and baicalin (p < .05). Moreover, the expressions of Nestin and
      NSE were enhanced by ginsenoside Rb1 and baicalin (p < .05), while the GFAP level
      was only affected by ginsenoside Rb1 (p < .05) when compared with the model
      group. CONCLUSION: Ginsenoside Rb1 and baicalin might promote the proliferation
      and differentiation of endogenous NSCs in AD rat model.

PMID- 29038008
TI  - Fibrinogen cleavage products and Toll-like receptor 4 promote the generation of
      programmed cell death 1 ligand 2-positive dendritic cells in allergic asthma.
AB  - BACKGROUND: Inhaled protease allergens preferentially trigger TH2-mediated
      inflammation in allergic asthma. The role of dendritic cells (DCs) on induction
      of TH2 cell responses in allergic asthma has been well documented; however, the
      mechanism by which protease allergens induce TH2-favorable DCs in the airway
      remains unclear. OBJECTIVE: We sought to determine a subset of DCs responsible
      for TH2 cell responses in allergic asthma and the mechanism by which protease
      allergens induce the DC subset in the airway. METHODS: Mice were challenged
      intranasally with protease allergens or fibrinogen cleavage products (FCPs) to
      induce allergic airway inflammation. DCs isolated from mediastinal lymph nodes
      were analyzed for surface phenotype and T-cell stimulatory function. Anti-Thy1.2
      and Mas-TRECK mice were used to deplete innate lymphoid cells and mast cells,
      respectively. Adoptive cell transfer, bone marrow DC culture, anti-IL-13, and
      Toll-like receptor (TLR) 4-deficient mice were used for further mechanistic
      studies. RESULTS: Protease allergens induced a remarkable accumulation of TH2
      favorable programmed cell death 1 ligand 2 (PD-L2)+ DCs in mediastinal lymph
      nodes, which was significantly abolished in mice depleted of mast cells and, to a
      lesser extent, innate lymphoid cells. Mechanistically, FCPs generated by protease
      allergens triggered IL-13 production from wild-type mast cells but not from TLR4
      deficient mast cells, which resulted in an increase in the number of PD-L2+ DCs.
      Intranasal administration of FCPs induced an increase in numbers of PD-L2+ DCs in
      the airway, which was significantly abolished in TLR4- and mast cell-deficient
      mice. Injection of IL-13 restored the PD-L2+ DC population in mice lacking mast
      cells. CONCLUSION: Our findings unveil the "protease-FCP-TLR4-mast cell-IL-13"
      axis as a molecular mechanism for generation of TH2-favorable PD-L2+ DCs in
      allergic asthma and suggest that targeting the PD-L2+ DC pathway might be
      effective in suppressing allergic T-cell responses in the airway.

PMID- 29038009
TI  - Advances in mechanisms of allergic disease in 2016.
AB  - This review highlights advances in mechanisms of allergic disease, particularly
      type 2 innate lymphoid cells; TH2 lymphocytes; eicosanoid regulation of
      inflammation; extracellular vesicles in allergic responses; IL-33; microbiome
      properties, especially as they relate to mucosal barrier function; and a series
      of findings concerning the allergic inflammatory cells eosinophils, basophils,
      and mast cells. During the last year, mechanistic advances occurred in
      understanding type 2 innate lymphoid cells, particularly related to their
      response to ozone, involvement with experimental food allergy responses, and
      regulation by IL-33. Novel ways of regulating TH2 cells through epigenetic
      regulation of GATA-3 through sirtuin-1, a class III histone deacetylase, were
      published. The understanding of eicosanoid regulation of inflammation increased
      and focused on additional properties of phospholipase A2 and the role of
      prostaglandin D2 and its receptors and inhibitory prostaglandin E2 pathways.
      Mechanisms through which extracellular vesicles are released and contribute to
      allergic responses were reported. There was a deeper appreciation of mucosal
      barrier function, the epithelial alarmin IL-33, and the microbiome. Finally,
      there were advances concerning allergic inflammatory cells (mast cells,
      basophils, and eosinophils) that will undoubtedly have an effect on disease
      understanding and new therapeutic strategies.

PMID- 29038010
TI  - Peripheral Visual Fields in ABCA4 Stargardt Disease and Correlation With Disease
      Extent on Ultra-widefield Fundus Autofluorescence.
AB  - PURPOSE: To evaluate the disease extent on ultra-widefield fundus
      autofluorescence (UWF-FAF) in patients with ABCA4 Stargardt disease (STGD) and
      correlate these data with functional outcome measures. DESIGN: Retrospective
      cross-sectional study. METHODS: Setting: Kellogg Eye Center, University of
      Michigan. STUDY POPULATION: Sixty-five patients with clinical diagnosis and
      proven pathogenic variants in the ABCA4 gene. Observational Procedures: The UWF
      FAF images were obtained using Optos (200 degrees) and classified into 3 types.
      Functional testing included kinetic widefield perimetry, full-field
      electroretinogram (ffERG), and visual acuity (VA). All results were evaluated
      with respect to UWF-FAF classification. MAIN OUTCOME MEASURES: Classification of
      UWF-FAF; area comprising the I4e, III4e, and IV4e isopters; ffERG patterns; and
      VA. RESULTS: For UWF-FAF, 27 subjects (41.5%) were classified as type I, 17
      (26.2%) as type II, and 21 (32.4%) as type III. The area of each isopter
      correlated inversely with the extent of the disease and all isopters were able to
      detect differences among UWF-FAF types (IV4e, P = .0013; III4e, P = .0003; I4e, P
      < .0001 = 3.93e-8). ffERG patterns and VA were also different among the 3 UWF-FAF
      types (P < .001 = 6.61e-6 and P < .001 = 7.3e-5, respectively). CONCLUSION:
      Patients with widespread disease presented with more constriction of peripheral
      visual fields and had more dysfunction on ffERG and worse VA compared to patients
      with disease confined to the macula. UWF-FAF images may provide information for
      estimating peripheral and central visual function in STGD.

PMID- 29038011
TI  - Macular Fluid Reduces Reproducibility of Choroidal Thickness Measurements on
      Enhanced Depth Optical Coherence Tomography.
AB  - PURPOSE: To determine if different types of retinal fluid in the central macula
      affect the reproducibility of choroidal thickness (CT) measurements on enhanced
      depth imaging optical coherence tomography (EDI-OCT). DESIGN: Retrospective
      reliability analysis. METHODS: EDI-OCT images were obtained and the choroidal
      scleral junction was analyzed through semiautomated segmentation. CT was measured
      at the fovea and averaged across the central 3-mm horizontal segment. Demographic
      data, central macular thickness, and type of fluid present were recorded.
      Intragrader and intergrader repeatability were assessed using the intraclass
      correlation coefficient (ICC) and coefficient of repeatability (CR). RESULTS: Of
      124 eyes analyzed, 60 (48.4%) had diabetic macular edema, 32 (25.8%) had
      neovascular age-related macular degeneration, and 32 (25.8%) had other causes of
      fluid. Intergrader ICC (CR) was 0.95 (74.1 MUm) and 0.96 (63.9 MUm) for subfoveal
      and average CT, respectively. CR was similar across various causes of retinal
      fluid, but was worst for subretinal fluid compared to intraretinal or sub-retinal
      pigment epithelial fluid. CR also worsened with increasing choroidal thickness,
      but was not affected by retinal thickness. Intragrader repeatability was
      generally greater than intergrader values, and followed the same trend.
      CONCLUSIONS: The presence of macular fluid reduces CT measurement
      reproducibility, particularly in eyes with subretinal fluid and greater choroidal
      thickness. A difference of 74.1 MUm in subfoveal CT or 63.9 MUm in average CT may
      be necessary to detect true clinical change in eyes with macular fluid.

PMID- 29038013
TI  - A transcriptomics assessment of oxygen-temperature interactions reveals novel
      candidate genes underlying variation in thermal tolerance and survival.
AB  - While single stress responses are fairly well researched, multiple, interactive
      stress responses are not-despite the obvious importance thereof. Here, using D.
      melanogaster, we investigated the effects of simultaneous exposures to low O2
      (hypoxia) and varying thermal conditions on mortality rates, estimates of thermal
      tolerance and the transcriptome. We used combinations of 21 (normoxia), 10 or
      5kPa O2 with control (23 degrees C), cold (4 degrees C) or hot (31 degrees C)
      temperature exposures before assaying chill coma recovery time (CCRT) and heat
      knock down time (HKDT) as measures of cold and heat tolerance respectively. We
      found that mortality was significantly affected by temperature, oxygen partial
      pressure (PO2) and the interaction between the two. Cold treatments resulted in
      low mortality (<5%), regardless of PO2 treatment; while hot treatments resulted
      in higher mortality (~20%), especially at 5kPa O2 which was lethal for most flies
      (~80%). Both CCRT and HKDT were significantly affected by temperature, but not
      PO2, of the treatments, and the interaction of temperature and PO2 was non
      significant. Hot treatments led to significantly longer CCRT, and shorter HKDT in
      comparison to cold treatments. Global gene expression profiling provided the
      first transcriptome level response to the combined stress of PO2 and temperature,
      showing that stressful treatments resulted in higher mortality and induced
      transcripts that were associated with protein kinases, catabolic processes
      (proteases, hydrolases, peptidases) and membrane function. Several genes and
      pathways that may be responsible for the protective effects of combined PO2 and
      cold treatments were identified. We found that urate oxidase was upregulated in
      all three cold treatments, regardless of the PO2. Small heat shock proteins Hsp22
      and Hsp23 were upregulated after both 10 and 21kPa O2-hot treatments.
      Collectively, the data from PO2-hot treatments suggests that hypoxia does
      exacerbate heat stress, through an as yet unidentified mechanism. Hsp70B and an
      unannotated transcript (CG6733) were significantly differentially expressed after
      5kPa O2-cold and 10kPa O2-hot treatments relative to their controls.
      Downregulation of these transcripts was correlated with reduced thermal tolerance
      (longer CCRT and shorter HKDT), suggesting that these genes may be important
      candidates for future research.

PMID- 29038014
TI  - Effects of lignins as diet components on the physiological activities of a lower
      termite, Coptotermes formosanus Shiraki.
AB  - We investigated the effects of lignins as diet components on the physiological
      activities of a lower termite, Coptotermes formosanus Shiraki. Artificial diets
      composed of polysaccharides with and without purified lignins (milled-wood
      lignins) from Japanese cedar (softwood), Japanese beech (hardwood), and rice
      (grass), were fed to C. formosanus workers. The survival and body mass of the
      workers as well as the presence of three symbiotic protists in the hindguts of
      the workers were then periodically examined. The survival rates of workers fed on
      diets containing lignins were, regardless of the lignocellulose diet sources,
      significantly higher than those of workers fed on only polysaccharides. In
      addition, it was clearly observed that all the tested lignins have positive
      effects on the maintenance of two major protists in the hindguts of C. formosanus
      workers, i.e., Pseudotrichonympha grassii and Holomastigotoides hartmanni.
      Overall, our data suggest that the presence of lignin is crucial to maintaining
      the physiological activities of C. formosanus workers during their lignocellulose
      decomposition. Our data also suggested that some components, possibly minerals
      and/or non-structural carbohydrates, in grass lignocellulose negatively affect
      the survival of C. formosanus workers as well as the present rate of the
      symbiotic protists in their hindguts.

PMID- 29038012
TI  - The structure of the actin-smooth muscle myosin motor domain complex in the rigor
      state.
AB  - Myosin-based motility utilizes catalysis of ATP to drive the relative sliding of
      F-actin and myosin. The earliest detailed model based on cryo-electron microscopy
      (cryoEM) and X-ray crystallography postulated that higher actin affinity and
      lever arm movement were coupled to closure of a feature of the myosin head dubbed
      the actin-binding cleft. Several studies since then using crystallography of
      myosin-V and cryoEM structures of F-actin bound myosin-I, -II and -V have
      provided details of this model. The smooth muscle myosin II interaction with F
      actin may differ from those for striated and non-muscle myosin II due in part to
      different lengths of important surface loops. Here we report a ~6 A resolution
      reconstruction of F-actin decorated with the nucleotide-free recombinant smooth
      muscle myosin-II motor domain (MD) from images recorded using a direct electron
      detector. Resolution is highest for F-actin and the actin-myosin interface (3.5-4
      A) and lowest (~6-7 A) for those parts of the MD at the highest radius. Atomic
      models built into the F-actin density are quite comparable to those previously
      reported for rabbit muscle actin and show density from the bound ADP. The atomic
      model of the MD, is quite similar to a recently published structure of vertebrate
      non-muscle myosin II bound to F-actin and a crystal structure of nucleotide free
      myosin-V. Larger differences are observed when compared to the cryoEM structure
      of F-actin decorated with rabbit skeletal muscle myosin subfragment 1. The
      differences suggest less closure of the 50 kDa domain in the actin bound skeletal
      muscle myosin structure.

PMID- 29038015
TI  - Why is there no impact of the host species on the cold tolerance of a generalist
      parasitoid?
AB  - For generalist parasitoids such as those belonging to the Genus Aphidius, the
      choice of host species can have profound implications for the emerging
      parasitoid. Host species is known to affect a variety of life history traits.
      However, the impact of the host on thermal tolerance has never been studied.
      Physiological thermal tolerance, enabling survival at unfavourable temperatures,
      is not a fixed trait and may be influenced by a number of external factors
      including characteristics of the stress, of the individual exposed to the stress,
      and of the biological and physical environment. As such, the choice of host
      species is likely to also have implications for the thermal tolerance of the
      emerging parasitoid. The current study aimed to investigate the effect of cereal
      aphid host species (Sitobion avenae, Rhopalosiphum padi and Metopolophium
      dirhodum) on adult thermal tolerance, in addition to sex and size, of the aphid
      parasitoids Aphidius avenae, Aphidius matricariae and Aphidius rhopalosiphi.
      Results revealed no effect of host species on the cold tolerance of the emerging
      parasitoid, as determined by CTmin and Chill Coma, for all parasitoid species.
      Host species significantly affected the size of the emerging parasitoid for A.
      rhopalosiphi only, with individuals emerging from R. padi being significantly
      larger than those emerging from S. avenae, although this did not correspond to a
      difference in thermal tolerance. Furthermore, a significant difference in the
      size of male and female parasitoids was observed for A. avenae and A.
      matricariae, although, once again this did not correspond to a difference in cold
      tolerance. It is suggested that potential behavioural thermoregulation via host
      manipulation may act to influence the thermal environment experienced by the wasp
      and thus wasp thermal tolerance and, in doing so, may negate physiological
      thermal tolerance or any impact of the aphid host.

PMID- 29038016
TI  - Age, sex, mating status, but not social isolation interact to shape basal
      immunity in a group-living insect.
AB  - Immunity is a crucial but costly trait. Individuals should therefore adjust their
      investment into immunity to their condition and infection risks, which are often
      determined by their age, sex, mating status and social environment. However,
      whether and how these four key factors can interact to shape basal immunity
      remains poorly understood. Here, we tested the simultaneous effects of these
      factors on hemocyte concentration and phenoloxidase activity in adults of the
      European earwig. We found that hemocyte concentration increased with age, and
      that this increase was stronger in males. We also found an age-dependent increase
      in phenoloxidase activity in males and virgin females, but not in mated females.
      However, the two immune parameters were independent of social isolation. Overall,
      our results reveal that a complex interplay between age, sex and mating status
      determines basal immunity and stress the importance of interactions in our
      understanding of immune investment.

PMID- 29038018
TI  - Undervalued and ignored: Are humans poorly adapted to energy-dense foods?
AB  - In many species the capacity to accurately differentiate the energy density
      (kcal/g) of foods is critical because it greatly improves efficiency in foraging.
      In modern humans this ability remains intact and is expressed in a selective
      preference for types of fruit and vegetables that contain more calories. However,
      humans evolved consuming these low energy-dense foods (typically < 1.75 kcal/g)
      and it remains unclear whether they can also discriminate more energy-dense foods
      that now feature in modern Western diets. In two experiment participants (both N
      = 40) completed four tasks that assessed the 'value' of different sets of 22
      foods that ranged in energy density (0.1 kcal/g-5.3 kcal/g and range 0.1 kcal/g
      to 6.2 kcal/g in Experiment 1 and 2, respectively). In Experiment 1 three
      measures (expected fullness, calorie estimation, and food choice), and in foods
      less than approximately 1.5 kcal/g (typically fruits and vegetables), the
      relationship between perceived value and energy density is linear. Above this, we
      observed clear compressive functions, indicating relative and progressive
      undervaluation of higher energy-dense foods. The fourth task (rated liking)
      failed to provide evidence for any relationship with energy density. In
      Experiment 2 the same pattern was replicated in measures of expected fullness,
      and in two different assessments of subjective calorie content. Consistent with
      the concept of 'evolutionary discordance,' this work indicates that modern human
      physiology is poorly adapted to evaluate foods that have a historically unusual
      (high) energy density. This has implications both for our understanding of how
      'modern' energy-dense foods affect choice and energy intake, and for strategies
      aimed at removing calories from highly energy-rich foods.

PMID- 29038017
TI  - Fetal growth interacts with multilocus genetic score reflecting dopamine
      signaling capacity to predict spontaneous sugar intake in children.
AB  - BACKGROUND: We have shown that intrauterine growth restriction (IUGR) leads to
      increased preference for palatable foods at different ages in both humans and
      rodents. In IUGR rodents, altered striatal dopamine signaling associates with a
      preference for palatable foods. OBJECTIVES: Our aim was to investigate if a
      multilocus genetic score reflecting dopamine-signaling capacity is differently
      associated with spontaneous palatable food intake in children according to the
      fetal growth status. METHODS: 192 four-year old children from a community sample
      from Montreal and Hamilton, Canada, were classified according to birth weight and
      administered a snack test meal containing regular as well as palatable foods.
      Intrauterine growth restriction was based on the birth weight ratio below 0.85;
      children were genotyped for polymorphisms associated with dopamine (DA)
      signaling, with the hypofunctional variants (TaqIA-A1 allele, DRD2-141C Ins/Ins,
      DRD4 7-repeat, DAT1-10-repeat, Met/Met-COMT) receiving the lowest scores, and a
      composite score was calculated reflecting the total number of the five genotypes.
      Macronutrient intake during the Snack Test was the outcome. RESULTS: Adjusting
      for z-score BMI at 48 months and sex, there was a significant interaction of the
      genetic profile and fetal growth on sugar intake [beta^ = -4.56, p = 0.04],
      showing a positive association between the genetic score and sugar intake in IUGR
      children, and no association in non-IUGR children. No significant interactions
      were seen in other macronutrients. CONCLUSIONS: Variations in a genetic score
      reflecting DA signaling are associated with differences in sugar intake only in
      IUGR children, suggesting that DA function is involved in this behavioral feature
      in these children. This may have important implications for obesity prevention in
      this population.

PMID- 29038019
TI  - Establishment of a cell-based wound healing assay for bio-relevant testing of
      wound therapeutics.
AB  - INTRODUCTION: Predictive in vitro testing of novel wound therapeutics requires
      adequate cell-based bio-assays. Such assays represent an integral part during
      preclinical development as pre-step before entering in vivo studies. Simple
      "scratch tests" based on defected skin cell monolayers exist, however these can
      solely be used for testing liquids, as cell monolayer destruction and excessive
      hydration limit their applicability for (semi-)solid systems like wound
      dressings. In this context, a cell-based wound healing assay is introduced for
      rapid and predictive testing of wound therapeutics independent of their physical
      state in a bio-relevant environment. METHODS: A novel wound healing assay was
      established for bio-relevant and predictive testing of (semi-) solid wound
      therapeutics. RESULTS: The assay allows for physiologically relevant hydration of
      the tested wound therapeutics at the air-liquid interface and their removal
      without cell monolayer disruption. In a proof-of-concept study, the applicability
      and discriminative power could be demonstrated by examining unloaded and drug
      loaded wound dressings with two different established wound healing actives
      (dexpanthenol and metyrapone) and their effect on skin cell behavior. The
      influence of the released drug on the cells' healing behavior could successfully
      be monitored over time. Wound size assessment after 96h resulted in an eight fold
      smaller wound area for drug treated models compared to the ones treated with
      unloaded fibers and non-treated wounds. DISCUSSION: This assay provides valuable
      first insights towards the establishment of a valid screening and evaluation tool
      for preclinical wound therapeutic development from liquid to (semi-)solid systems
      to improve predictability in a simple, yet standardized way.

PMID- 29038020
TI  - The Ca2+/CaMKK2 axis mediates the telbivudine induced upregulation of creatine
      kinase: Implications for mechanism of antiviral nucleoside analogs' side effect.
AB  - Telbivudine (LdT), a widely prescribed anti-hepatitis B virus (HBV) drug for the
      treatment of chronic Hepatitis B (CHB), causes adverse reactions ranging from
      creatine kinase (CK) elevation to myopathy. The purpose of this study was to
      explore the mechanism(s) of LdT induced CK elevation. The effects of LdT on
      mitochondrial morphology and proteins (TK2 and beta-actin), oxidative stress,
      intracellular Ca2+ levels, Ca2+-related signaling pathway (CaMKK2/AMPK), and Ca2+
      related biomarkers such as superoxide dismutase (SOD) and malondialdehyde (MDA)
      were assessed in human skeletal muscle cells (HSKMCs). The results showed that
      LdT induced a dose-dependent increase in CK activity in HSKMCs, without affecting
      mitochondrial morphology, and TK2 and beta-actin protein levels, following 72 h
      of treatment. In addition, LdT increased Ca2+ production, ROS generation, MDA and
      lipid peroxide (LPO) levels, and activated the CaMKK2/AMPK signaling pathway.
      Moreover, these effects were attenuated by the BAPIA-AM (the calcium chelator).
      We also confirmed the presence of relevant markers (MDA, LPO, and SOD) in serum
      from CHB patients after LdT treatment, and found that CK was positively
      correlated with MDA and LPO, and negatively associated with SOD. These findings
      indicate that LdT induces CK elevation and oxidative stress associated with
      imbalance of intracellular Ca2+ in HSKMCs, suggesting that Ca2+/CaMKK2 axis
      imbalance may underlie human LdT-induced CK elevation. The present findings
      provide a solid basis for assessing the mechanism of drug-induced CK elevation,
      which can help develop new tools for the prevention and treatment of diseases
      associated with drug-induced CK elevation.

PMID- 29038021
TI  - Detailed characterization of Synechocystis PCC 6803 ferredoxin:NADP+
      oxidoreductase interaction with model membranes.
AB  - Direct interaction of ferredoxin:NADP+ oxidoreductase (FNR) with thylakoid
      membranes was postulated as a part of the cyclic electron flow mechanism. In
      vitro binding of FNR to digalactosyldiacylglycerol and
      monogalactosyldiacylglycerol membranes was also shown. In this paper we deal with
      the latter interaction in more detail describing the effect for two FNR forms of
      Synechocystis PCC 6803. The so-called short FNR (sFNR) is homologous to FNR from
      higher plant chloroplasts. The long FNR (lFNR) form contains an additional
      domain, responsible for the interaction with phycobilisomes. We compare the
      binding of both sFNR and lFNR forms to native and non-native lipids. We also
      include factors which could modulate this process: pH change, temperature change,
      presence of ferredoxin, NADP+ and NADPH and heavy metals. For the lFNR, we also
      include phycobilisomes as a modulating factor. The membrane binding is generally
      faster at lower pH. The sFNR was binding faster than lFNR. Ferredoxin isoforms
      with higher midpoint potential, as well as NADPH and NADP+, weakened the binding.
      Charged lipids and high phosphate promoted the binding. Heavy metal ions
      decreased the rate of membrane binding only when FNR was preincubated with them
      before injection beneath the monolayer. FNR binding was limited to surface lipid
      groups and did not influence hydrophobic chain packing. Taken together, FNR
      interaction with lipids appears to be non-specific, with an electrostatic
      component. This suggests that the direct FNR interaction with lipids is most
      likely not a factor in directing electron transfer, but should be taken into
      account during in vitro studies.

PMID- 29038022
TI  - A conjugate of decyltriphenylphosphonium with plastoquinone can carry cyclic
      adenosine monophosphate, but not cyclic guanosine monophosphate, across
      artificial and natural membranes.
AB  - The present study demonstrated for the first time the interaction between
      adenosine 3',5'-cyclic monophosphate (cAMP), one of the most important signaling
      compounds in living organisms, and the mitochondria-targeted antioxidant
      plastoquinonyl-decyltriphenylphosphonium (SkQ1). The data obtained on model
      liquid membranes and human platelets revealed the ability of SkQ1 to selectively
      transport cAMP, but not guanosine 3',5'-cyclic monophosphate (cGMP), across both
      artificial and natural membranes. In particular, SkQ1 elicited translocation of
      cAMP from the source to the receiving phase of a Pressman-type cell, while
      showing low activity with cGMP. Importantly, only conjugate with plastoquinone,
      but not dodecyl-triphenylphosphonium, was effective in carrying cAMP. In human
      platelets, SkQ1 also appeared to serve as a carrier of cAMP, but not cGMP, from
      outside to inside the cell, as measured by phosphorylation of the vasodilator
      stimulated phosphoprotein. The SkQ1-induced transfer of cAMP across the plasma
      membrane found here can be tentatively suggested to interfere with cAMP signaling
      pathways in living cells.

PMID- 29038023
TI  - The impact of length variations in the L2 loop on the structure and thermal
      stability of non-specific porins: The case of OmpCs from the Yersinia
      pseudotuberculosis complex.
AB  - Porins are integral proteins of the outer membranes of gram-negative bacteria. In
      membranes, they exist as homotrimers and the L2 loops contribute to their
      stability. Comparison of OmpC porins of the Yersinia pseudotuberculosis complex
      with other enterobacterial porins demonstrated L2 loop length diversity, which is
      caused by varying numbers of dipeptide/tripeptide repeats. The OmpC porins are
      highly homologous to each other, and they can be subdivided into five isoforms
      based on their L2 loop structure. Optical spectroscopy and SDS-PAGE experiments
      revealed that particularities of the L2 loops affected the structure and thermal
      stability of the porins. Thermal denaturation studies showed that porins with
      shorter loops, compared to porins with longer loops, had more stable tertiary and
      less stable secondary and quaternary structures. According to our comparative
      modeling results, the L2 loops differ in their structure by adopting different
      spatial positions and forming different polar bonds with a neighbor monomer. The
      replacement of asparagine with arginine at the C-terminus of the L2 loop shifts
      the loop upwards and causes the loss of contacts with the arginine clusters
      within the pores. The increase in the length of these loops ensures that they
      shift down toward the pore and restore their contacts with arginines on the
      channel wall, as is the case in classical nonspecific porins. Despite the fact
      that the surface charge density varies considerably among the OmpC porins, the L2
      loops form a typical negatively charged region in the center of the trimer.

PMID- 29038024
TI  - Structural insights of a self-assembling 9-residue peptide from the C-terminal
      tail of the SARS corona virus E-protein in DPC and SDS micelles: A combined high
      and low resolution spectroscopic study.
AB  - In recent years, several studies based on the interaction of self-assembling
      short peptides derived from viroporins with model membranes, have improved our
      understanding of the molecular mechanism of corona virus (CoV) infection under
      physiological conditions. In this study, we have characterized the mechanism of
      membrane interaction of a short, 9-residue peptide TK9 (T55VYVYSRVK63) that had
      been derived from the carboxyl terminal of the Severe Acute Respiratory Syndrome
      (SARS) corona virus (SARS CoV) envelope (E) protein. The peptide has been studied
      for its physical changes in the presence of both zwitterionic DPC and negatively
      charged SDS model membrane micelles, respectively, with the help of a battery of
      biophysical techniques including two-dimensional solution state NMR spectroscopy.
      Interestingly, in both micellar environments, TK9 adopted an alpha helical
      conformation; however, the helical propensities were much higher in the case of
      DPC compared to those of SDS micelle, suggesting that TK9 has more specificity
      towards eukaryotic cell membrane than the bacterial cell membrane. The
      orientation of the peptide TK9 also varies in the different micellar
      environments. The peptide's affinity was further manifested by its pronounced
      membrane disruption ability towards the mammalian compared to the bacterial
      membrane mimic. Collectively, the in-depth structural information on the
      interaction of TK9 with different membrane environments explains the host
      specificity and membrane orientation owing to subsequent membrane disruption
      implicated in the viral pathogenesis.

PMID- 29038025
TI  - Assessment of the cervical spine denticulate ligament using MRI volumetric
      sequence: Comparison between 1.5 Tesla and 3.0 Tesla.
AB  - BACKGROUND: Denticulate ligaments (DLs) are pial extensions on each side of the
      spinal cord, comprising about 20 to 21 pairs of fibrous structures connecting the
      dura mater to the spinal cord. These ligaments are significant anatomical
      landmarks in the surgical approach to intradural structures. To our knowledge,
      there is no previous study on the detection of DLs using MRI. METHODS: After IRB
      approval, we retrospectively evaluated 116 consecutive MRI scans of the cervical
      spine, using the volumetric sequence 3D COSMIC, 65 and 51 studies with 1.5T and
      3.0T respectively. We did not include trauma and tumor cases. Two independent
      radiologists assessed the detection of cervical spine DLs independently and
      blinded for each cervical vertebral level. We compared the frequency of detection
      of these ligaments in 1.5 Tesla and 3.0 Tesla MRI using Fisher exact test
      considering P<0.05 as significant. We evaluated interobserver agreement with
      Kappa coefficient. RESULTS: We observed high detection frequency of the cervical
      spine DLs using both 1.5T (70 to 91%) and 3.0T (68 to 98%). We found no
      statistically significant difference in the detection frequency of ligaments
      between the 1.5T and 3.0T MRI in all vertebral levels. Using 3.0T, radiologists
      identified ligaments better in higher vertebral levels than for lower cervical
      levels (P=0.0003). Interobserver agreement on the identification of DL was poor
      both for 1.5T (k=0.3744; CI 95% 0.28-0.46) and 3.0T (k=0.3044; CI 95% 0.18-0.42)
      MRI. CONCLUSIONS: Radiologists identified most of the cervical DLs using
      volumetric MRI acquisition. Our results suggest 1.5T and 3.0T MRI performed
      similarly in the detection of DLs.

PMID- 29038026
TI  - Proteodynamics in aging human T cells - The need for its comprehensive study to
      understand the fine regulation of T lymphocyte functions.
AB  - Cellular life depends mostly on the creation, modification, interactions and
      destruction of proteins. This is true for every cell, including human T
      lymphocytes. One way these cells can ascertain the fidelity and at least partial
      functionality of their proteomes under constant attack of irreversible
      modulations (e.g., ROS- or glycation-dependent) is proteostasis. However, with
      cellular aging proteostasis progressively fails and proteostenosis (decreased
      amounts and functionalities of remaining proteins) occurs. There are several
      mechanisms involved in the modulation and protection of the proteome in the T
      cells which include mainly multiple layers of vesicle-bound and cytoplasmic
      proteases (e.g., lysosomal and proteasomal ones) acting mostly by degradation of
      obsolete and age-modified proteins. Recently it was shown that another not yet so
      widely known system consisting of obligatorily calcium-dependent cysteine
      proteases, the calpains and their inhibitor, the calpastatin serves in T cells as
      a dual switch, either activating or inactivating different proteins depending on
      intracellular conditions. Thus the proteolytic elimination of altered proteins as
      well as modulation of activity of those remaining leads to dynamic change of
      proteome composition and function (proteodynamics) in aging lymphocytes, so far
      in an almost unknown way. Aging T cell proteodynamics requires further
      comprehensive analysis of the resulting lysoproteomic patterns and their changes.

PMID- 29038027
TI  - Tumor necrosis factor-alpha and soluble TNF-alpha receptor responses in young vs.
      middle-aged males following eccentric exercise.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) has been shown to be
      implicated in both muscle regeneration and muscle wasting. However, it remains
      unclear whether TNF-alpha is responsible for the age-related losses in muscle
      size and function. Also, due to the high clearance rate of TNF-alpha from
      circulation, analyzing the circulating levels of soluble TNF-alpha receptors 1
      and 2 (STNFR1 and STNFR2) may provide a better indication of inflammatory events.
      The aim of this study was to examine changes in circulating concentrations of TNF
      alpha, STNFR1, and STNFR2 following acute eccentric exercise in young (YA) and
      middle-aged (MA) men. METHODS AND MATERIALS: Nine YA (N=9, 21.8+/-2.2y, 179.5+/
      4.9cm, 91.2+/-12.2kg, 21.8+/-4.3% body fat) and ten MA (N=10, 47.0+/-4.4y,
      176.8+/-7.6cm; 96.0+/-21.5kg, 25.4+/-5.3% body fat) men completed an acute muscle
      damaging protocol (MDP). Blood samples were obtained at baseline (BL),
      immediately (IP), 30-minute (30P), 60-minute (60P), 120-minute (120P), 24-hour
      (24H), and 48-hour (48H) post-MDP. Lower body performance was assessed via
      isokinetic dynamometer at BL, IP, 120P, 24H, and 48H. RESULTS: YA displayed
      higher values of peak torque (p=0.023) and mean torque (p=0.036) at BL. No
      significant group differences were observed for markers of muscle damage or TNF
      alpha. Plasma concentrations of TNF-alpha were unchanged following MDP. STNFR1
      concentrations were significantly higher in the YA group compared to MA
      (p=0.036). Significant time effects were observed for STNFR1 (p<0.001) and STNFR2
      (p=0.001). With both groups combined, serum STNFR1 was decreased at 30P
      (p=0.001), while STNFR2 was decreased at 30P (p=0.008), 60P (p=0.003), and 120P
      (p=0.002) relative to BL. CONCLUSIONS: The pro-inflammatory response to muscle
      damage does not appear to decline at middle age when individuals are
      recreationally trained. However, young men showed significantly higher serum
      STNFR1 concentrations than middle age men. This may suggest that natural
      inhibitors of TNF-alpha decline as early as middle age.

PMID- 29038028
TI  - Adiponectin and sporadic Alzheimer's disease: Clinical and molecular links.
AB  - Obesity has been consistently associated with Alzheimer's disease (AD) though the
      exact mechanisms by which it influences cognition are still elusive and subject
      of current research. Adiponectin, the most abundant adipokine in circulation, is
      inversely correlated with adipose tissue dysfunction and seems to be a central
      player in this association. In fact, different signalling pathways are shared by
      adiponectin and proteins involved in AD pathophysiology and considerable amount
      of evidence supports its direct and indirect influence on beta-amyloid and tau
      aggregates formation. In this paper we present a critical review of cellular,
      animal and clinical studies which have contributed to a more thorough
      understanding of the extent to which adiponectin influences the risk of
      developing AD as well as its progression. Finally, the effect of
      acetylcholinesterase inhibitors on circulating adiponectin levels, possible
      therapeutic applications and future research strategies are also discussed.

PMID- 29038029
TI  - Expanding the spectrum of TBL1XR1 deletion: Report of a patient with brain and
      cardiac malformations.
AB  - The TBL1XR1 gene product is a nuclear protein ubiquitously produced. The protein
      is a component of SMRT/N-CoR co-repressor complexes and participates in the
      molecular switch of specific gene transcription. Deletions of the TBL1XR1 gene
      have been described in two families to date, both presenting intellectual
      disability and dysmorphisms. Rare recurrent chromosomal micro-rearrangements,
      particularly those involving single genes, represent a challenge for clinicians
      to ensure correlation with phenotype due to the paucity of previously described
      cases. Here we present a patient harbouring a TBL1XR1 gene deletion detected by
      chromosome microarray analysis. In addition to intellectual disability, the
      patient presents dysmorphic features and multiple cardiac malformations, together
      with brain malformation, thus contributing to the phenotypic characterization of
      this rare microdeletion and to the TBL1XR1 gene function.

PMID- 29038031
TI  - The cognitive psychology and neuroscience of naming people.
AB  - The use of proper names enables us to designate entities, including people, at a
      very specific level of categorization: the unique entity or the individual. The
      paper presents a general overview of psychological/cognitive and neuroscientific
      studies that have compared the production of proper names, in particular people's
      names, with the production of common nouns during the last thirty years. The
      search for specific brain correlates of proper naming included single-case and
      group studies of patients with brain lesions, and studies utilizing functional
      neuroimaging or brain electrical stimulation with healthy participants. These
      studies have led neuroscientists to hypothesize that the recall of proper names
      involves a rather complex network including mainly left frontal and temporal
      regions. Behavioural evidence supports the view that proper names are more
      difficult to recall than common names, and scientists have proposed different
      explanations for this relative difficulty. Finally, several new directions for
      future research are proposed to improve our understanding of both cognitive
      processes and their brain correlates involved during proper name recall.

PMID- 29038032
TI  - Feasibility of sacrocolpopexy by outpatient laparoscopic surgery.
AB  - INTRODUCTION: Sacrocolpopexy (SP) is a common intervention that is most often
      performed by laparoscopy. This intervention usually involves standard
      hospitalization. Evaluation of whether this procedure can be safely carried out
      by outpatient hospitalization (OH) is of considerable relevance. The aim of our
      study was hence to evaluate the feasibility of SP by OH. PATIENTS AND METHODS:
      This was an observational multicenter study that included women who underwent SP
      by OH. The main assessment criteria were the success rate of OH and the rate of
      rehospitalisation in the month following the intervention. The secondary
      assessment criteria were the rate of complications in the month following the
      surgery, the level of patient satisfaction evaluated by a set of straightforward
      questions and two validated questionnaires (the Patient Global Impression of
      Improvement [PGI-I] and the Core questionnaire for the assessment of Patient
      Satisfaction with general Day care [COPS-D]). RESULTS: There were 55 women
      operated on by OH. The success rate for the OH was 49/55 (89.1% (80.7-97.3%)). Of
      the 31/55 women (56.4%) who answered the PGI-I questionnaire, 27/31 (87.1%)
      stated that the intervention improved their condition. Of the 30/55 women who
      answered the COPS-D questionnaire, 26/30 (86.7%) women were "satisfied" or "very
      satisfied" with the conditions for their discharge from the OH. CONCLUSION: The
      success rate for SP by OH was high in this study, with a very substantial level
      of patient satisfaction. These findings nonetheless ought to be confirmed with
      series involving higher numbers of women.

PMID- 29038033
TI  - Cervical preparation prior to surgical abortion in real-life conditions and
      factors driving the prescription: A national observational study.
AB  - INTRODUCTION: Few data exist to document the real-life practices regarding
      surgical abortion for first trimester abortion, in particular regarding the
      cervical preparation. Using a large national sample of French hospitals
      practicing surgical abortion, we explore actual practices and described drugs
      used for cervical preparation and factors that influence the prescription.
      METHODS: From December 2013 to July 2014, a longitudinal, prospective,
      multicenter, non-interventional study was undertaken with the main objective of
      assessing in real-life conditions the modalities of cervical preparation prior
      surgical abortion in women with less than 14 weeks of amenorrhea. RESULTS: A
      total of 542 patients agreed to participate and were included by 36 French
      private or public hospitals. Among 36 active centers, 31 (86.1%) implemented
      cervical preparation prior surgical abortion, in line with French and
      international clinical guidelines. For the 510 patients who underwent surgical
      abortions, the most frequent prescribed treatment was misoprostol only (224/510,
      43.9% of patients), following by mifepristone only (167/510, 32.8%) and a
      combination of misoprostol and mifepristone (99/510, 19.4%). Finally, four
      factors were identified as independent contributor to guide the treatment
      prescribed for cervical preparation: woman work situation, gestational age
      intensity of center's activity regarding the number of abortions yearly and mode
      of anesthesia. CONCLUSIONS: Our study showed an almost systematic implementation
      of cervical preparation before surgical abortion in France. Misoprostol only was
      the most commonly prescribed treatment for the cervix preparation, followed by
      mifepristone only. Several factors may have a significant influence on the type
      of cervical preparation chosen by physicians.

PMID- 29038034
TI  - Environmental characteristics of early childhood education and care centres and
      young children's weight status: A systematic review.
AB  - The aim of this systematic review was to summarize ECEC environmental correlates
      of weight status in children under the age of 6years. Six databases (PubMed,
      PsycINFO, CINAHL, SPORTDiscus, Scopus, and Web of Science) were searched until
      March 2017. Observational studies examining the relationship between ECEC
      environmental characteristics and weight status in children aged 0-6years were
      included. Data was extracted using a predesigned form. Eight studies,
      representing 4862 children, met the inclusion criteria. Twenty-two environmental
      characteristics were identified and classified into four domains (physical,
      political, economic, and sociocultural); of these, six correlates were found.
      'Active environment' 'sedentary opportunities', 'active play time', 'high sugar
      and high fat served', 'educators' weight' and 'educators' habitual physical
      activity level' were associated with weight status in young children. However,
      for most environmental characteristics examined, strong evidence is not available
      yet, due to variations across studies on the measures of environmental
      characteristics and analytical methodologies. Stronger empirical evidence in
      greater quantity is needed. Future studies in this area are recommended to
      investigate the environmental influence using an ecological approach and to
      examine the potential mediators, with a focus on the settings of family-based
      centres and samples representing toddlers and/or infants.

PMID- 29038030
TI  - Dynamic functional connectivity impairments in early schizophrenia and clinical
      high-risk for psychosis.
AB  - Individuals at clinical high-risk (CHR) for psychosis are characterized by
      attenuated psychotic symptoms. Only a minority of CHR individuals convert to full
      blown psychosis. Therefore, there is a strong interest in identifying
      neurobiological abnormalities underlying the psychosis risk syndrome. Dynamic
      functional connectivity (DFC) captures time-varying connectivity over short time
      scales, and has the potential to reveal complex brain functional organization.
      Based on resting-state functional magnetic resonance imaging (fMRI) data from 70
      healthy controls (HCs), 53 CHR individuals, and 58 early illness schizophrenia
      (ESZ) patients, we applied a novel group information guided ICA (GIG-ICA) to
      estimate inherent connectivity states from DFC, and then investigated group
      differences. We found that ESZ patients showed more aberrant connectivities and
      greater alterations than CHR individuals. Results also suggested that disease
      related connectivity states occurred in CHR and ESZ groups. Regarding the
      dominant state with the highest contribution to dynamic connectivity, ESZ
      patients exhibited greater impairments than CHR individuals primarily in the
      cerebellum, frontal cortex, thalamus and temporal cortex, while CHR and ESZ
      populations shared common aberrances mainly in the supplementary motor area,
      parahippocampal gyrus and postcentral cortex. CHR-specific changes were also
      found in the connections between the superior frontal gyrus and calcarine cortex
      in the dominant state. Our findings suggest that CHR individuals generally show
      an intermediate functional connectivity pattern between HCs and SZ patients but
      also have unique connectivity alterations.

PMID- 29038036
TI  - Overexpression of Notch ligand Delta-like-1 by dendritic cells enhances their
      immunoregulatory capacity and exerts antiallergic effects on Th2-mediated
      allergic asthma in mice.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells, and Notch ligand
      Delta-like-1 (DLL1) on DCs was implicated in type 1T helper (Th1)
      differentiation. In this study, we produced genetically engineered bone marrow
      derived DCs that expressed DLL1 (DLL1-DCs) by adenoviral transduction. DLL1-DCs
      exerted a fully mature phenotype, and had positive effects on expression levels
      of interleukin (IL)-12 and costimulatory molecules. Coculture of allogeneic T
      cells with ovalbumin (OVA)-pulsed DLL1-DCs enhanced T cell proliferative
      responses and promoted Th1 cell differentiation. Furthermore, adoptive transfer
      of OVA-stimulated DLL1-DCs into asthmatic mice alleviated the cardinal features
      of allergic asthma, including immunoglobulin E (IgE) production, airway
      hyperresponsiveness (AHR), airway inflammation, and production of Th2-type
      cytokines. Notably, enhanced levels of the Th1-biased IgG2a response and
      interferon (IFN)-gamma production were observed in these mice. Taken together,
      these data indicate that DLL1-DCs promoted Th1 cell development to alter the
      Th1/Th2 ratio and ameliorate Th2-mediated allergic asthma in mice.

PMID- 29038035
TI  - Biochemical and pharmacological characterization of three opioid-nociceptin
      hybrid peptide ligands reveals substantially differing modes of their actions.
AB  - In an attempt to design opioid-nociceptin hybrid peptides, three novel bivalent
      ligands, H-YGGFGGGRYYRIK-NH2, H-YGGFRYYRIK-NH2 and Ac-RYYRIKGGGYGGFL-OH were
      synthesized and studied by biochemical, pharmacological, biophysical and
      molecular modelling tools. These chimeric molecules consist of YGGF sequence, a
      crucial motif in the N-terminus of natural opioid peptides, and Ac-RYYRIK-NH2,
      which was isolated from a combinatorial peptide library as an antagonist or
      partial agonist that inhibits the biological activity of the endogenously
      occurring heptadecapeptide nociceptin. Solution structures for the peptides were
      studied by analysing their circular dichroism spectra. Receptor binding
      affinities were measured by equilibrium competition experiments using four highly
      selective radioligands. G-protein activating properties of the multitarget
      peptides were estimated in [35S]GTPgammaS binding tests. The three compounds were
      also measured in electrically stimulated mouse vas deferens (MVD) bioassay. H
      YGGFGGGRYYRIK-NH2 (BA55), carrying N-terminal opioid and C-terminal nociceptin
      like sequences interconnected with GGG tripeptide spacer displayed a tendency of
      having either unordered or beta-sheet structures, was moderately potent in MVD
      and possessed a NOP/KOP receptor preference. A similar peptide without spacer H
      YGGFRYYRIK-NH2 (BA62) exhibited the weakest effect in MVD, more alpha-helical
      periodicity was present in its structure and it exhibited the most efficacious
      agonist actions in the G-protein stimulation assays. The third hybrid peptide Ac
      RYYRIKGGGYGGFL-OH (BA61) unexpectedly displayed opioid receptor affinities,
      because the opioid message motif is hidden within the C-terminus. The designed
      chimeric peptide ligands presented in this study accommodate well into a group of
      multitarget opioid compounds that include opioid-non-opioid peptide dimer
      analogues, dual non-peptide dimers and mixed peptide- non-peptide bifunctional
      ligands.

PMID- 29038037
TI  - Brain inflammatory cytokines and microglia morphology changes throughout
      hibernation phases in Syrian hamster.
AB  - Hibernators tolerate low metabolism, reduced cerebral blood flow and hypothermia
      during torpor without noticeable neuronal or synaptic dysfunction upon arousal.
      Previous studies found extensive changes in brain during torpor, including
      synaptic rearrangements, documented both morphologically and molecularly. As such
      adaptations may represent organ damage, we anticipated an inflammatory response
      in brain during specific hibernation phases. In this study, signs of inflammation
      in the brain were investigated in the Syrian hamster hippocampus (Mesocricetus
      Auratus) both during hibernation (torpor and arousal phases) and in summer and
      winter euthermic animals. mRNA expression of the pro-inflammatory cytokines TNF
      alpha, IL-6 and IL-1beta was quantified by RT-qPCR. Morphological changes of
      microglia were studied by immunohistochemistry staining for IBA-1. Activation of
      microglia based on retraction and thickening of the dendritic branches and an
      increase in cell body size was quantified by calculation of cell body size to
      total cell size ratio. Expression of pro-inflammatory cytokines was upregulated
      early in arousal (90 min), and normalized after 8 h of arousal. Substantial loss
      of microglia ramification was found throughout torpor and early arousal together
      with a 2-fold increase in the cell body size to total cell size ratio. Notably,
      microglia changes were fully reversed in late arousal (8 h) to euthermic levels.
      These results demonstrate an upregulation of inflammatory cytokines and signs of
      microglia activation during hibernation, which completely resolves by late
      arousal. Activation of this response may serve to prevent or offset brain damage
      resulting from the substantial physiological changes accompanying torpor and
      their rapid change during early arousal.

PMID- 29038038
TI  - Global proteome and phosphoproteome dynamics indicate novel mechanisms of vitamin
      C induced dormancy in Mycobacterium smegmatis.
AB  - : Vitamin C has been found to affect mycobacteria in multiple ways, including
      increasing susceptibility to antimicrobial drugs, inducing dormancy, and having a
      bactericidal effect. However, the regulatory events mediating vitamin C related
      adaptations remain largely elusive. Ser/Thr/Tyr protein phosphorylation plays an
      important regulatory role in mycobacteria, contributing to environmental
      adaptation, including dormancy and drug resistance. This study utilised the model
      organism, Mycobacterium smegmatis, and TiO2 phosphopeptide enrichment combined
      with mass spectrometry-based proteomics methods to elucidate the mycobacterial
      signalling and regulatory response to sub-lethal concentrations of vitamin C.
      After initial validation of peptide spectra, 224 non-redundant phosphosites in
      154 proteins were retained with high confidence. Data analysis revealed that 30
      peptides were differentially phosphorylated with Vitamin C treatment, including
      novel phosphosites found on both PknG and GarA. Of these significant proteins, we
      validated 11 by parallel reaction monitoring of high-confidence phosphopeptides.
      Interestingly, 17/30 phosphopeptides were annotated as part of transmembrane
      proteins, suggesting that it is likely vitamin C triggers typical signal
      transduction events in which the protein periplasmic domain perceives
      environmental signals and the cytoplasmic domain is then phosphorylated. Finally,
      the diverse nature of phosphorylated proteins involved in signalling, transport,
      and carbohydrate biosynthesis indicates the extent of such regulatory
      phosphorylation events. BIOLOGICAL SIGNIFICANCE: Our findings provide new
      mechanistic insight into a coordinated network of signalling and regulatory
      responses to sub-lethal vitamin C in Mycobacterium smegmatis and provide evidence
      that vitamin C is able to act as a novel extracellular signalling molecule.
      Vitamin C treatment caused changes in both the proteome and phosphoproteome
      associated with response to oxidative stress, a shift in metabolic regulation and
      progression toward dormancy, as well as phospho-dependent activation of specific
      secretory pathways and activation of specific two component and Ser/Thr/Tyr
      protein kinase activities. This study confirms the potential of vitamin C as
      convenient means to study aspects of mycobacterial dormancy, including those
      regulated at post-translational level.

PMID- 29038039
TI  - Hysteroscopic Transcervical Resection for Atypical Polypoid Adenomyoma of the
      Uterus: A Valid, Fertility-Preserving Option.
AB  - STUDY OBJECTIVE: To evaluate hysteroscopic transcervical resection (TCR) for
      atypical polypoid adenomyoma of the uterus (APA). DESIGN: Retrospective study
      (Canadian Task Force classification II-2). SETTING: Single tertiary hospital.
      PATIENTS: Women who underwent TCR for APA at Kawasaki Municipal Hospital between
      2003 and 2015. INTERVENTIONS: Clinical records were obtained. MEASUREMENTS AND
      MAIN RESULTS: Thirty-five patients with APA were evaluated. The median patient
      age was 35 years (range, 23-43 years), and the median tumor diameter was 22 mm
      (range, 9-51 mm). The median duration of observation after the first TCR was 34.0
      months (range, 4.2-133.7 months). In 19 patients, the tumor recurred after the
      first TCR. A second TCR was performed in 13 patients, 11 of whom experienced
      recurrence. A third TCR was performed in 7 patients, all 7 of whom experienced
      recurrence. A fourth TCR was performed in 4 patients, 3 of whom experienced
      recurrence. The recurrence rate after the second TCR was higher than that after
      the first TCR (71.4%-84.6% vs 54.3%; p < .01, t test). The median disease-free
      interval was 12.4 months after the first TCR, 15.3 months after the second TCR,
      10.5 months after the third TCR, and 10.9 months after the fourth TCR. Seven
      patients progressed to endometrial cancer; however, there was no mortality. Six
      of the 35 patients conceived, and 4 had a normal spontaneous delivery.
      CONCLUSION: Owing to disease-free intervals that follow treatment, TCR is a
      promising treatment modality as a fertility-preserving option for patients with
      APA under careful observation. Twenty percent of patients with APA develop
      cancer; however, the present study showed no mortality.

PMID- 29038040
TI  - Hysteroscopic Intrauterine Adhesiolysis Using a Blunt Spreading Dissection
      Technique With Double-action Forceps.
AB  - STUDY OBJECTIVE: To demonstrate step-by-step the technique of hysteroscopic
      adhesiolysis (HA) by means of a blunt spreading technique using double-action
      forceps to dissect and restore the layer between the anterior and posterior
      uterine walls in a patient with severe intrauterine adhesions (IUAs),
      particularly in cases in which the endometrial lining is obscured on ultrasound
      imaging and the endometrial cavity is completely occluded on hysteroscopy.
      DESIGN: A step-by-step explanation of the technique using videos and pictures
      (educative video) (Canadian Task Force Classification III). SETTING: A university
      affiliated hospital. PATIENT: A 36-year-old, gravida 3, para 1, abortus 2 woman
      presenting with amenorrhea for 5 months after surgical termination of a 53-day
      intrauterine pregnancy. She had no cyclic lower abdominal pain. Ultrasound
      revealed an obscure endometrial stripe and no obvious hematometra. Both the urine
      human chorionic gonadotropin test and the progesterone withdrawal test were
      negative. One month before admission, hysteroscopic adhesiolysis failed because
      the uterine cavity was inaccessible because of adhesions completely occluding the
      lower uterine cavity. Additionally, the uterine cavity could not be explored with
      a probe because the anatomic layer of the endometrial lining could not be easily
      identified by transabdominal ultrasound. INTERVENTION: HA using a blunt spreading
      dissection technique with double-action forceps to restore the uterine cavity
      followed by "ploughing" of the intrauterine scar tissue using cold scissors [1].
      MEASUREMENTS AND MAIN RESULTS: An intraoperative technique with commentary
      highlighting tips for a successful dissection. The uterine cavity was
      successfully restored using the blunt spreading dissection technique. There were
      no complications, including false uterine wall passage, uterine perforation, or
      fluid overload. Postoperative hysteroscopy at 1 month revealed an almost normal
      uterine cavity. CONCLUSIONS: HA using a blunt spreading dissection technique to
      restore the uterine cavity is a simple, effective, and safe hysteroscopic skill,
      especially when the endometrial stripe is obscured on ultrasound imaging and
      exploring the uterine cavity by means of a probe has failed. Furthermore, this
      technique may serve as an alternative to resectoscopic techniques because it uses
      cold forceps and scissors, which provide better protection for the endometrium.

PMID- 29038041
TI  - Minilaparoscopy vs Standard Laparoscopy for Sentinel Node Dissection: A Pilot
      Study.
AB  - OBJECTIVE: To compare 3-mm minilaparoscopy and standard 5-mm laparoscopy for
      sentinel lymph node (SLN) detection in apparent early-stage endometrial cancer
      (EC). DESIGN: Retrospective study (Canadian Task Force classification II-2).
      SETTING: Two academic research centers. PATIENTS: Consecutive women with apparent
      early-stage EC who underwent surgical staging with SLN detection between November
      2015 and April 2016. INTERVENTIONS: The surgical approach was a total
      laparoscopic extrafascial hysterectomy plus bilateral salpingo-oophorectomy and
      SLN detection. Systematic lymphadenectomy was performed in selected cases. In all
      patients, SLN detection was performed with cervical injection of indocyanine
      green and the use of an optical camera with a near-infrared high-intensity light
      source for detection of fluorescence imaging. All patients who underwent a
      minilaparoscopic approach (using one 5-mm scope and three 3-mm ancillary trocars)
      have been enrolled at the University of Insubria, whereas at the San Gerardo
      Hospital, standard laparoscopy was performed with one 10-mm scope and three 5-mm
      ancillary trocars. MEASUREMENTS AD MAIN RESULTS: A total of 38 patients were
      enrolled, including 15 (39.5%) in the 3-mm group and 23 (60.5%) in the 5-mm
      group. No between-group differences were found in terms of demographic and tumor
      characteristics. Bilateral SLNs were detected in 73.3% of the patients in the 3
      mm group and in 73.9% in the 5-mm group. Operative time, blood loss, hemoglobin
      drop, hospital stay, and the incidence and severity of complications were similar
      in the 2 groups. One patient (4.3%) in the standard 5-mm group had a positive SLN
      result (a micrometastasis in the left external iliac SLN). No positive SLNs were
      detected in the 3-mm group. CONCLUSION: Minilaparoscopic SLN biopsy appears to be
      a promising and feasible technique for EC staging. Further research is warranted
      to investigate the possible benefits of 3-mm instruments in this specific
      setting.

PMID- 29038042
TI  - Relationship between Catamenial Pneumothorax or Non-catamenial Pneumothorax and
      Endometriosis.
AB  - STUDY OBJECTIVE: To evaluate the clinical characteristics of women presenting
      with catamenial pneumothorax and compare them with those with noncatamenial
      pneumothorax. DESIGN: A case-control study (Canadian Task Force II-2). SETTING: A
      multicenter study. PATIENTS: Forty-two women with pneumothorax: 21 women had
      catamenial pneumothorax (study group), and 21 were age-matched women with
      noncatamenial pneumothorax (control group). INTERVENTIONS: All patients underwent
      video-assisted thoracoscopy and pleural biopsy. We also evaluated the presence
      and stage of pelvic endometriosis in 16 women with catamenial pneumothorax who
      had undergone laparoscopic surgery. MEASUREMENTS AND MAIN RESULTS: The number of
      known episodes of catamenial pneumothorax before treatment was between 2 and 8
      episodes. Symptoms were mainly chest pain and shortness of breath; 1 patient had
      hemoptysis. The prevalence of right-sided pneumothorax was 95.2% in the study
      group and 57.1% in the control group (p = .004). Besides 2 cases with complete
      collapse of the right lung, most of the cases in the study group had apical
      pneumothorax. Pelvic endometriosis was found in 15 of 16 women (93.7%), mainly
      stage 3 or 4, and thoracic endometriosis in 12 of 20 women (60%). None of the
      patients in the control group had thoracic endometriosis. CONCLUSION: Thoracic
      endometriosis is found in over half of women with catamenial pneumothorax but
      absent in those with noncatamenial pneumothorax. Right apical pneumothorax is
      predominant in women with catamenial pneumothorax. Endometriosis plays an
      important role in the mechanism of catamenial pneumothorax.

PMID- 29038043
TI  - Laparoscopic Excision of a Scar Pregnancy and Isthmocele Repair.
AB  - STUDY OBJECTIVE: Laparoscopic excision of a scar pregnancy and isthmocele repair
      with a barbed suture. DESIGN: A step-by-step explanation of the laparoscopic
      excision technique of a scar pregnancy and isthmocele repair. SETTING: Cesarean
      scar pregnancy occurs as a result of attachment of the products of conception to
      the uterine scar [1-3]. In the present case, a 34-year-old, gravida 4, para 1
      patient with a history of 1 miscarriage and 1 ectopic pregnancy was diagnosed
      with type 2 cesarean scar pregnancy at 7 weeks of gestation. Dilation and
      curretage was performed at the 8th week of gestation to terminate the pregnancy.
      On ultrasonography performed 1 month later, placental material underlying the
      isthmocele was observed. Her beta human chorionic gonadotropin level was 13 836
      mIU/mL. She was followed up for 1.5 months until the beta human chorionic
      gonadotropin levels were negative. However, the mass underneath the scar had
      grown larger, measuring up to 5 * 6 cm. Laparoscopy was performed because the
      patient reported vaginal spotting and pelvic pain. The incision was sutured with
      a synthetic absorbable unidirectional barbed suture (Stratafix Knotless Tissue
      Control Device; Ethicon Inc., Somerville, NJ). No residual scar defect was
      visible on follow-up ultrasonography 1 week and 1 month after surgery.
      CONCLUSION: Barbed sutures ease the repair of uterine scar defects and can
      provide ideal reapproximation of thick myometrial tissue. Laparoscopic treatment
      of a scar pregnancy and isthmocele repair are effective and safe modes of
      treatment.

PMID- 29038044
TI  - Readmission Rates after Same-Day Discharge Compared with Postoperative Day 1
      Discharge after Benign Laparoscopic Hysterectomy.
AB  - STUDY OBJECTIVE: To determine if there is a difference in readmission rates after
      same-day discharge compared with postoperative day 1 discharges after
      laparoscopic hysterectomy. DESIGN: A retrospective cohort study with 1:2
      propensity score matching (Canadian Task Force classification II-2). SETTING:
      American College of Surgeons National Surgical Quality Improvement Program
      database. PATIENTS: Women undergoing benign laparoscopic total or supracervical
      hysterectomy or laparoscopic-assisted vaginal hysterectomy with or without
      adnexal surgery between the years 2010 to 2015. INTERVENTIONS: Three thousand
      thirty-two low-risk women discharged on postoperative day 0 and 6064 women
      discharged on postoperative day 1 were included in the analysis. MEASUREMENTS AND
      MAIN RESULTS: The overall readmission rate was 1.8%; after same-day discharge,
      the readmission rate was 2.2%, and after postoperative day 1 discharge the
      readmission rate was 1.7% (p = .10). After logistic regression analysis, smoking
      (adjusted odds ratio [aOR] = 2.06; 95% confidence interval [CI], 1.49-2.88),
      nonwhite race (aOR = 1.53; 95% CI, 1.1007-2.14), and cystoscopy (aOR = 2.05; 95%
      CI, 1.49-2.82) were associated with an increased risk of readmission. CONCLUSION:
      There was no statistically significant difference in readmission rates after
      laparoscopic hysterectomy between women discharged on the day of surgery or
      postoperative day 1.

PMID- 29038045
TI  - Effects of procalcitonin-guided treatment on antibiotic use and need for
      mechanical ventilation in patients with acute asthma exacerbation: Meta-analysis
      of randomized controlled trials.
AB  - OBJECTIVE: The primary outcome was to determine whether serum procalcitonin
      guided antibiotic therapy can reduce antibiotic exposure in patients with an
      acute exacerbation of asthma presenting to the primary care facility or emergency
      department, or during hospital admission. The secondary outcome was the need for
      mechanical ventilation. METHODS: An extensive literature search was performed to
      identify randomized controlled clinical trials (published in English) that
      compared serum procalcitonin-guided antibiotic therapy versus antibiotic use
      according to physician's discretion for adult participants with mild, moderate,
      or severe acute asthma exacerbations. RESULTS: Four randomized controlled trials
      evaluating 457 patients were included in this meta-analysis, with significant
      homogeneity observed among these studies. Procalcitonin-based protocols decreased
      antibiotic prescriptions (relative risk 0.58, 95% confidence interval 0.50-0.67).
      The conclusion regarding the difference between the two groups in the need for
      mechanical ventilation (relative risk 1.10, 95% confidence interval 0.62-1.94)
      was guarded due to inadequate power and the potential for type II error. The
      overall quality of evidence was also limited by the lack of double-blinding.
      CONCLUSIONS: These data suggest a potential benefit for the use of serum
      procalcitonin in guiding antibiotic therapy in patients with an acute asthma
      exacerbation and advocates the need for more randomized controlled trials.

PMID- 29038046
TI  - Multiple reversals of strand asymmetry in molluscs mitochondrial genomes, and
      consequences for phylogenetic inferences.
AB  - Strand asymmetry in nucleotide composition is a remarkable feature of animal
      mitochondrial genomes. The strand-specific bias in the nucleotide composition of
      the mtDNA has been known to be highly problematic for phylogenetic analyses.
      Here, the strand asymmetry was compared across 140 mollusc species and analyzed
      for a mtDNA fragment including twelve protein-coding genes. The analyses show
      that almost all species in Gastropoda (except Heterobranchia) and all species in
      Bivalvia present reversals of strand bias. The skew values on individual genes
      for all codon positions (P123), third codon positions (P3), and fourfold
      redundant third codon positions (P4FD) indicated that CG skews are the best
      indicators of strand asymmetry. The differences in the patterns of strand
      asymmetry significantly influenced the amino acid composition of the encoded
      proteins. These biases are most striking for the amino acids Valine, Cysteine,
      Asparagine and Threonines, which appear to have evolved asymmetrical exchanges in
      response to shifts in nucleotide composition. Molluscs with strong variability of
      genome architectures (ARs) are usually characterized by a reversal of the usual
      strand bias. Phylogenetic analyses show that reversals of asymmetric mutational
      constraints have consequences on the phylogenetic inferences, as taxa
      characterized by reverse strand bias (Heterobranchia and Bivalvia) tend to group
      together due to long-branch attraction (LBA) artifacts. Neutral Transitions
      Excluded (NTE) model did not overcome the problem of heterogeneous biases present
      in molluscs mt genomes, suggested it may not be appropriate for molluscs mt
      genome data. Further refinement phylogenetic models may help us better understand
      internal relationships among these diverse organisms.

PMID- 29038047
TI  - Joint groupwise registration and ADC estimation in the liver using a B-value
      weighted metric.
AB  - PURPOSE: The purpose of this work is to develop a groupwise elastic multimodal
      registration algorithm for robust ADC estimation in the liver on multiple breath
      hold diffusion weighted images. METHODS: We introduce a joint formulation to
      simultaneously solve both the registration and the estimation problems. In order
      to avoid non-reliable transformations and undesirable noise amplification, we
      have included appropriate smoothness constraints for both problems. Our metric
      incorporates the ADC estimation residuals, which are inversely weighted according
      to the signal content in each diffusion weighted image. RESULTS: Results show
      that the joint formulation provides a statistically significant improvement in
      the accuracy of the ADC estimates. Reproducibility has also been measured on real
      data in terms of the distribution of ADC differences obtained from different b
      values subsets. CONCLUSIONS: The proposed algorithm is able to effectively deal
      with both the presence of motion and the geometric distortions, increasing
      accuracy and reproducibility in diffusion parameters estimation.

PMID- 29038048
TI  - The influence of DOCA-salt hypertension and chronic administration of the FAAH
      inhibitor URB597 on KCa2.3/KCa3.1-EDH-type relaxation in rat small mesenteric
      arteries.
AB  - The aim of this study was to examine the influence of deoxycorticosterone acetate
      salt (DOCA-salt) hypertension and chronic treatment with the fatty acid amide
      hydrolase inhibitor, URB597, on small and intermediate conductance calcium
      activated potassium channels and endothelium-dependent hyperpolarization
      (KCa2.3/KCa3.1-EDH) in rat small mesenteric arteries (sMAs). The EDH-type
      response was investigated, in endothelium-intact sMAs using a wire myograph, by
      examining acetylcholine-evoked vasorelaxation in the presence of Nomega-nitro-L
      arginine methyl ester and indomethacin (inhibitors of nitric oxide synthase and
      cyclooxygenase, respectively). In normo- and hypertension the efficacy of EDH
      type relaxation was similar and inhibition of KCa2.3 and KCa3.1 by UCL1684 and
      TRAM-34, respectively, given alone or in combination, attenuated EDH-mediated
      vasorelaxation. KCa3.1 expression and NS309 (KCa2.3/KCa3.1 activator)-induced
      relaxation was reduced in sMAs of DOCA-salt rats. Endothelium denudation and
      incubation with UCL1684 and TRAM-34 attenuated the maximal NS309-evoked
      vasorelaxation in both groups. URB597 had no effect in functional studies, but
      increased the expression of KCa3.1 in the sMAs. KCa2.3/KCa3.1-EDH-mediated
      relaxation was maintained in the sMAs of DOCA-salt rats despite endothelial
      dysfunction and down-regulation of KCa3.1. Furthermore, KCa3.1 played a key role
      in the EDH-type dilator response of sMAs in normo- and hypertension. The
      hypotensive effect of URB597 is independent of KCa2.3/KCa3.1-EDH-type relaxation.

PMID- 29038049
TI  - Inhibition of EGFR attenuates fibrosis and stellate cell activation in diet
      induced model of nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic
      liver disease. NAFLD begins with steatosis and advances to nonalcoholic
      steatohepatitis (NASH) and cirrhosis. The molecular mechanisms involved in NAFLD
      progression are not understood. Based on recent studies showing dysregulation of
      epidermal growth factor receptor (EGFR) in animal models of liver injury, we
      sought to determine if inhibition of EGFR mitigates liver fibrosis and HSC
      activation in NAFLD. We utilized the high fat diet (HFD)-induced murine model of
      liver injury to study the role of EGFR in NAFLD. The lipid accumulation,
      oxidative stress, hepatic stellate cell (HSC) activation and matrix deposition
      were examined in the liver tissues. We also evaluated the EGFR signaling pathway,
      ROS activation and pro-fibrogenic phenotype in oxidized low density lipoproteins
      (ox-LDL) challenged cultured HSCs. We demonstrate that EGFR was phosphorylated in
      liver tissues of HFD murine model of NAFLD. Inhibition of EGFR prevented diet
      induced lipid accumulation, oxidative stress, and HSC activation and matrix
      deposition. In cultured HSCs, we show that ox-LDL caused rapid activation of the
      EGFR signaling pathway and induce the production of reactive oxygen species. EGFR
      also mediated HSC activation and promoted a pro-fibrogenic phenotype. In
      conclusion, our data demonstrate that EGFR plays an important role in NAFLD and
      is an attractive target for NAFLD therapy.

PMID- 29038050
TI  - Mechanisms of DNA damage repair in adult stem cells and implications for cancer
      formation.
AB  - Maintenance of genomic integrity in tissue-specific stem cells is critical for
      tissue homeostasis and the prevention of deleterious diseases such as cancer.
      Stem cells are subject to DNA damage induced by endogenous replication mishaps or
      exposure to exogenous agents. The type of DNA lesion and the cell cycle stage
      will invoke different DNA repair mechanisms depending on the intrinsic DNA repair
      machinery of a cell. Inappropriate DNA repair in stem cells can lead to cell
      death, or to the formation and accumulation of genetic alterations that can be
      transmitted to daughter cells and so is linked to cancer formation. DNA
      mutational signatures that are associated with DNA repair deficiencies or
      exposure to carcinogenic agents have been described in cancer. Here we review the
      most recent findings on DNA repair pathways activated in epithelial tissue stem
      and progenitor cells and their implications for cancer mutational signatures. We
      discuss how deep knowledge of early molecular events leading to carcinogenesis
      provides insights into DNA repair mechanisms operating in tumours and how these
      could be exploited therapeutically.

PMID- 29038052
TI  - Serine/threonine protein kinase PpkA contributes to the adaptation and virulence
      in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a leading cause of nosocomial infections worldwide and
      has become a serious public health threat, which is attributed to a large extent
      to its extraordinary environmental adaptability and diverse virulence factors
      that result in infection and progression of pathogenesis. The eukaryote-type
      serine/threonine (Ser/Thr) protein kinases, known for playing major regulatory
      roles in eukaryotes, have been demonstrated to play a central role in regulating
      various bacterial cellular processes via catalyzing protein phosphorylation.
      Although PpkA, a Ser/Thr protein kinase first identified in P. aeruginosa, has
      been implicated in association with bacterial virulence, little is known about
      the protein. Therefore, in this study, to assess the potential role of PpkA in
      the regulation of P. aeruginosa environmental adaptation and virulence,
      variations of biofilm formation, pyocyanin production, tolerance to stress, cell
      invasion and plant virulence were determined in wild type PAO1, ppkA gene-deleted
      and complemented mutant strains. Our results indicate that the mutant strain
      lacking ppkA exhibited a significant decrease of biofilm formation and pyocyanin
      production, less tolerance to oxidative and osmotic stresses, inefficient
      invasion of host cells and a reduction of bacterial virulence. These findings
      provide new insight into the regulation of various cellular processes by PpkA;
      this is an important mechanism for adaptation and virulence in P. aeruginosa.

PMID- 29038051
TI  - Integrated approach reveals diet, APOE genotype and sex affect immune response in
      APP mice.
AB  - Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is
      influenced by genetic and environmental risk factors, such as inheritance of
      epsilon4 allele of APOE (APOE4), sex and diet. Here, we examined the effect of
      high fat diet (HFD) on amyloid pathology and expression profile in brains of AD
      model mice expressing human APOE isoforms (APP/E3 and APP/E4 mice). APP/E3 and
      APP/E4 mice were fed HFD or Normal diet for 3months. We found that HFD
      significantly increased amyloid plaques in male and female APP/E4, but not in
      APP/E3 mice. To identify differentially expressed genes and gene-networks
      correlated to diet, APOE isoform and sex, we performed RNA sequencing and applied
      Weighted Gene Co-expression Network Analysis. We determined that the immune
      response network with major hubs Tyrobp/DAP12, Csf1r, Tlr2, C1qc and Laptm5
      correlated significantly and positively to the phenotype of female APP/E4-HFD
      mice. Correspondingly, we found that in female APP/E4-HFD mice, microglia
      coverage around plaques, particularly of larger size, was significantly reduced.
      This suggests altered containment of the plaque growth and sex-dependent
      vulnerability in response to diet. The results of our study show concurrent
      impact of diet, APOE isoform and sex on the brain transcriptome and AD-like
      phenotype.

PMID- 29038054
TI  - Characterization of roles of SpaA in Erysipelothrix rhusiopathiae adhesion to
      porcine endothelial cells.
AB  - Erysipelothrix rhusiopathiae is the causative agent of animal erysipelas and
      human erysipeloid. The major protective antigen SpaA was suggested to play
      important roles in E. rhusiopathiae adhesion to host cells, but there is no
      specific study on SpaA pathogenic roles in adhesion. In this study we
      characterized direct and indirect roles of SpaA in E. rhusiopathiae adhesion to
      porcine endothelial cells. Recombinant E. rhusiopathiae SpaA (rSpaA) successfully
      binded to porcine iliac arterial endothelial cells. rSpaA protein pre-incubating
      endothelial cells or rSpaA antiserum pre-incubating E. rhusiopathiae
      significantly decreased E. rhusiopathiae adhesion to endothelial cells. rSpaA
      successfully binded host plasminogen and fibronectin, and rSpaA antiserum
      significantly decreased plasminogen-recruitment activity but not fibronectin
      recruitment activity of E. rhusiopathiae. In conclusion, SpaA acts as adhesin in
      E. rhusiopathiae adhesion to host cells, and SpaA binding activity to host
      plasminogen highly likely play roles in this adhesion.

PMID- 29038053
TI  - Flagellar motility, extracellular proteases and Vibrio cholerae detachment from
      abiotic and biotic surfaces.
AB  - Vibrio cholerae of serogroups O1 and O139, the causative agent of Asiatic
      cholera, continues to be a major global health threat. This pathogen utilizes
      substratum-specific pili to attach to distinct surfaces in the aquatic
      environment and the human small intestine and detaches when conditions become
      unfavorable. Both attachment and detachment are critical to bacterial
      environmental survival, pathogenesis and disease transmission. However, the
      factors that promote detachment are less understood. In this study, we examine
      the role of flagellar motility and hemagglutinin/protease (HapA) in vibrio
      detachment from a non-degradable abiotic surface and from the suckling mouse
      intestine. Flagellar motility facilitated V. cholerae detachment from abiotic
      surfaces. HapA had no effect on the stability of biofilms formed on abiotic
      surfaces despite representing >50% of the proteolytic activity present in the
      extracellular matrix. We developed a balanced lethal plasmid system to increase
      the bacterial cyclic diguanylate (c-di-GMP) pool late in infection, a condition
      that represses motility and HapA expression. Increasing the c-di-GMP pool
      enhanced V. cholerae colonization of the suckling mouse intestine. The c-di-GMP
      effect was fully abolished in hapA isogenic mutants. These results suggest that
      motility facilitates detachment in a substratum-independent manner. Instead, HapA
      appears to function as a substratum-specific detachment factor.

PMID- 29038055
TI  - Serum and brain purine levels in an experimental systemic infection of mice by
      Cryptococcus neoformans: Purinergic immunomodulatory effects.
AB  - The aim of this study was to evaluate the purine levels in serum and brains of
      mice experimentally infected by Cryptococcus neoformans. Twenty-four mice were
      divided into the following groups: a control group (n = 12; Group A) and an
      infection group with animals that were infected (n = 12; Group B) with a 0.3-mL
      intraperitoneal injection containing 1.7 * 107C. neoformans cells. Blood and
      brains were collected on days 20 (n = 6 per group) and 50 (n = 6 per group) post
      infection (PI). Histopathology and lung and brain cultures were performed to
      confirm fungal infection and tissue injuries. The levels of adenosine
      triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP),
      adenosine (ADO), inosine (INO), hypoxanthine (HYPO), xanthine (XAN) and uric acid
      (UA) in brains and serum were measured by high-performance liquid chromatography
      (HPLC) analysis. At both time points, histopathology analysis revealed
      inflammatory infiltrates in the brains and lungs of infected mice; clinical
      signs, such as piloerection and clinical respiratory distress, were also
      observed. ATP levels were significantly increased on days 20 and 50 PI (P < 0.01)
      in brains and serum, while brain ADO levels were increased on day 20 PI; brain
      and serum ADO levels were decreased on day 50 PI. Levels of ADP and AMP did not
      differ between groups (P > 0.05). Serum levels of INO of infected mice increased
      only on day 50 PI (P < 0.05). HYPO levels were reduced in the brains of infected
      animals at both experimental time points and were decreased in serum at day 50 PI
      (P < 0.05). XAN levels increased in infected mice only in serum on day 50 PI (P <
      0.05). The endogenous anti-oxidant uric acid was significantly increased in brain
      (days 20 and 50 PI) and decreased in serum. It is possible that C. neoformans
      infection in mice leads to a high ATP/ADO ratio that may improve the brain pro
      inflammatory response during both periods, while high ATP levels in serum act as
      a systemic signal to improve the immune response. Moreover, the anti-oxidant uric
      acid may increase in the brain to protect inflamed tissue from oxidative stress.

PMID- 29038056
TI  - Worldwide prevalence of viral infection in AECOPD patients: A meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a
      chronic progressive lung disease. On the other hand, viral infections of the
      airway are associated with the acute exacerbations of COPD. A systematic review
      and meta-analysis were performed to determine the prevalence rate of viral
      infections in acute exacerbations of COPD patients. METHODS: PubMed database was
      systematically searched for population-based prevalence studies (1930-2017).
      Fixed and random effects models were used for estimation of summary effect-sizes.
      Between-study heterogeneity and publication bias were also calculated. "Viral
      infections" and "COPD patients with exacerbations" were the two critical
      inclusion criteria. RESULTS: Twenty-eight studies were selected out of 26078
      articles for the present review. The overall estimation of the prevalence of
      viral infection was 0.374 (95% C.I: 0.359-0.388). Also, the evident heterogeneity
      of viral infection was observed among the studies (Cochran Q test, p value <
      0.001 and I-squared = 97.5%). The highest and lowest prevalence rate was related
      to rhinovirus and echovirus, respectively. Also, the results of this study showed
      that the prevalence of viral infection in exacerbated COPD patients has
      fluctuation during the years with a slight increase and decrease. CONCLUSIONS:
      The results of this systematic review demonstrated that respiratory viral
      infections have an important role in the acute exacerbation of COPD (AECOPD). In
      addition, determining the exact geographic epidemiology of these viruses is very
      important to manage the treatment of these infections.

PMID- 29038057
TI  - Bio-prospecting of coral (Porites lutea) mucus associated bacteria, Palk Bay
      reefs, Southeast coast of India.
AB  - Coral mucus is one of the key localization in the coral holobiont, as this serves
      as an energy rich substrate for a wide range of abundant, diverse and
      multifunctional microbiota. However, very little is known about the functional
      role of bacterial communities in their associations with corals. In the present
      study, a total of 48 isolates were obtained from Porites lutea wherein the genus
      of Bacillus sp. and Vibrio sp. were predominant. Bio-prospecting the coral mucus
      revealed the existence of (10.42%) antagonistic bacteria against the tested
      bacterial pathogens. Molecular taxonomy (16S rRNA) proved the identity of these
      antagonistic bacteria belong to Enterobacter cloacae (CM1), Bacillus subtilis
      (CM2), Bacillus sp. (CM11) and Bacillus marisflavi (CM12). The secondary
      screening emphasized that the ethyl acetate extract of B. subtilis showed strong
      antagonistic effect, followed by the chloroform extract of E. cloacae and ethyl
      acetate extract of B. marisflavi. The antagonistic activity was statistically
      confirmed by Principal Component Analysis and Hierarchical Cluster Analysis. The
      privileged coral mucus associated bacterial (CMAB) solvent extracts inhibited the
      bacterial pathogens at 100 MUg/ml (MIC) and ceased the growth at 200 MUg/ml
      (MBC). The hemolytic and brine shrimp lethality assays disclosed the non-toxic
      nature of solvent extracts of CMAB. Altogether, the present investigation brought
      out the diversity of bacteria associated with the mucus of P. lutea. In addition,
      bio-prospecting corroborated the CMAB as the potential source of
      pharmacologically important bioactive compounds against a wide range of bacterial
      pathogens.

PMID- 29038059
TI  - First isolation and characterization of the pathogenic Aeromonas veronii bv.
      veronii associated with ulcerative syndrome in the indigenous Pelophylax
      ridibundus of Al-Ahsaa, Saudi Arabia.
AB  - Virulent microbial pathogen infections are the main cause for amphibian decline
      worldwide. In the present study, a bacterial strain named RDL-2, which was
      isolated from the skin of infected Pelophylax ridibundus larvae, was cultured and
      then phenotypically and biochemically characterized using scanning electron
      microscopic observations and the API20E strip and Biolog Gen III MicroPlate
      system. The 16S rRNA gene sequence of this strain was also obtained and used in
      strain identification and phylogenetic analysis. Healthy P. ridibundus larvae
      were challenged with RDL-2 and monitored to determine clinical signs consistent
      with the disease. Strain RDL-2 was identified as Aeromonas veronii based on its
      phenotypic and biochemical characteristics and on 16S rRNA gene sequence and
      phylogenetic analysis: RDL-2 was gram-negative, rod-shaped, and reacted
      positively for 69 (73%) of the 94 traits analysed; its 16S rRNA gene sequence
      displayed the highest homology to that of A. veronii bv. veronii (99.9%). Koch's
      postulates were fulfilled confirming that A. veronii is the causal agent of
      ulcerative syndrome. Thus, this study is the first to report A. veronii as a
      marsh frog pathogen in the Al-Ahsaa region. The aetiology of A. veronii as a
      potential poikilothermic pathogen shown here will expedite the development of
      diagnostic tests and methods for eradicating ulcerative syndrome.

PMID- 29038058
TI  - Antimicrobial and synergistic activity of essential oils of Aloysia triphylla and
      Lippia alba against Aeromonas spp.
AB  - The objective of this study was to identify and quantify the chemical
      constituents, as well as the antimicrobial, antibiofilm and synergistic activity
      with florfenicol of essential oils of Aloysia triphylla (EOAT) and Lippia alba
      (EOLA) against Aeromonas spp. The antimicrobial activity of EOAT and EOLA was
      verified by the minimum bactericidal concentration (MBC) and the action against
      biofilm forming and consolidated biofilm. The synergistic activity of EOAT and
      EOLA with florfenicol was performed by the checkerboard technique. The main
      components of EOAT were alpha-citral (39.91%), E-carveol (25.36%) and limonene
      (21.52%), while that of EOLA was linalool (81.64%). Aeromonas spp. isolates
      showed sensitivity to both essential oils with MBC between 195.3 and 3125.0
      MUL/mL. Two isolates were classified as non-producing, three as moderate and 16
      as weak biofilm producers. The EOAT and EOLA interfered in the biofilm formation,
      from moderate to weak producers, but did not cause any interference in the
      consolidated biofilm. The EOAT and EOLA combined with florfenicol showed
      synergistic effect and reduced MBC. The EOAT and EOLA have potential for
      application as antimicrobial agents, as they interfere in the initial formation
      of biofilm and when combined with florfenicol, present a synergic effect with a
      reduction in the minimum dose of the antibiotic.

PMID- 29038060
TI  - Comparing Pain and Depressive Symptoms of Chronic Opioid Therapy Patients
      Receiving Dose Reduction and Risk Mitigation Initiatives With Usual Care.
AB  - : Dose reduction and risk mitigation initiatives have been recommended to reduce
      opioid-related risks among patients receiving chronic opioid therapy (COT), but
      questions remain over whether these initiatives worsen pain control and quality
      of life. In 2014 to 2015, we interviewed 1,588 adult COT patients within a health
      care system in Washington State and compared those who received dose reduction
      and risk mitigation initiatives in primary care clinics (intervention) with
      patients in comparable health care settings without initiatives (control). The
      primary outcomes were pain assessed using the pain, enjoyment, and general
      activity (PEG) scale, a 3-item scale to assess global pain intensity and
      interference, with secondary measures including depression (Patient Health
      Questionnaire-8 scale). Generalized estimating equations for linear regression
      models were used to estimate differences in mean scores between intervention and
      control sites. Estimated differences, adjusted for patient characteristics and
      weighted for nonresponse, between patients at intervention and control clinics
      were not clinically significant for the PEG (-.03, 95% confidence interval = -.25
      to .19) or Patient Health Questionnaire-8 (-.64, 95% confidence interval = -1.19
      to -.08). We found no evidence that COT patients in clinics with dose reduction
      and risk mitigation initiatives had clinically meaningful differences in pain
      intensity, interference with activities and enjoyment of life, or depressive
      symptoms compared with control health care settings. PERSPECTIVE: This article
      evaluates the effect of dose reduction and risk mitigation initiatives, such as
      those recently recommended by the Centers for Disease Control and Prevention, to
      reduce risks associated with COT on global pain and interference, depressive
      symptoms, and perceived pain relief and bothersomeness of side effects.

PMID- 29038061
TI  - Structural and Functional Brain Changes at Early and Late Stages of Complex
      Regional Pain Syndrome.
AB  - : Brain plasticity is demonstrated in complex regional pain syndrome (CRPS),
      although it is unclear how it modulates at different stages of CRPS. The
      observation that symptoms can progress over time suggests that the pattern of
      brain changes might also evolve. We measured structural and functional changes as
      well as sensorimotor integration at the early stage (ES) and late stage (LS) of
      CRPS. Twelve ES patients, 16 LS patients, and 16 age- and sex-matched controls
      were recruited. Gray matter (GM) volume was estimated using voxel-based
      morphometry. Cerebral perfusion was measured using arterial spin labeling,
      because it provides a measure of resting neural activity. Connectivity to
      sensorimotor regions was evaluated using blood-oxygen level-dependent images. The
      ES group showed reduced GM volume and perfusion in areas associated with spatial
      body perception, somatosensory cortex, and the limbic system, whereas the LS
      group exhibited increased perfusion in the motor cortex but no changes in GM
      volume. However, in the LS group, GM volume in areas associated with pain
      processing was negatively correlated with average pain levels, likely reflecting
      a response to ongoing pain. Furthermore, connectivity to sensorimotor cortex
      showed disruptions in regions associated with motor control and planning,
      implying impairment of higher-order motor control. PERSPECTIVE: This article
      presents brain changes at ES and LS of CRPS. We found different patterns of brain
      changes between these 2 stages. Understanding modulation of brain plasticity at
      different stages of CRPS could help understand the diversity in outcomes and
      treatment response and hopefully improve treatment planning.

PMID- 29038062
TI  - ZnO-based nanocarriers for drug delivery application: From passive to smart
      strategies.
AB  - Due to the excellent biocompatibility as well as the low cost, nanoscale ZnO
      shows a great potential in drug delivery application. The richness of the
      structures, easy modification and pleasant properties of nanoscale ZnO make these
      materials reasonable choices for drug delivery. In the recent decade, various ZnO
      nanostructures as well as nanohybrids have been carried out for optimizational
      drug loading and carrying. To control the drug release behavior, many nanoscale
      ZnO-based smart drug delivery systems which are responsive to particular stimuli
      via characteristics of ZnO (e.g. dissolution in acid, microwave absorbing,
      hydrophobic/hydrophilic transition) have been successfully synthesized. Herein,
      we review the recent exciting progress on the nanoscale ZnO-based drug delivery
      systems: from the passive to smart strategies.

PMID- 29038063
TI  - Spontaneous nano-emulsification: Process optimization and modeling for the
      prediction of the nanoemulsion's size and polydispersity.
AB  - The aim of the present study was to optimize the size and polydispersity of a
      lipid nanoemulsion as a function of the oil (Labrafac(r) WL1349), surfactant
      (Kolliphor(r) HS 15) and cosurfactant (Span(r) 80) phase composition and
      temperature. The nanoemulsions were prepared using a low-energy self
      emulsification method. The Z-average diameter and the polydispersity index (PDI)
      were modeled with mixture experiments. Nanoemulsions from 20nm to 120nm with
      PDI<0.2 were obtained at the three different tested temperatures (30 degrees C,
      50 degrees C and 90 degrees C). The nanoemulsion size was able to be controlled
      with the oil, surfactant and cosurfactant concentrations. Interestingly, the
      smallest PDIs were obtained at 30 degrees C, and the cosurfactant concentration
      was able to be adjusted to optimize the formulation and to obtain nanoemulsions
      in the 20-120nm range with a PDI smaller than 0.14. These nanoemulsions have
      shown a good stability at 4 degrees C in storage conditions and at 37 degrees C
      in diluted conditions.

PMID- 29038064
TI  - E-selectin targeted immunoliposomes for rapamycin delivery to activated
      endothelial cells.
AB  - Activated endothelial cells play a pivotal role in the pathology of inflammatory
      disorders and thus present a target for therapeutic intervention by drugs that
      intervene in inflammatory signaling cascades, such as rapamycin (mammalian target
      of rapamycin (mTOR) inhibitor). In this study we developed anti-E-selectin
      immunoliposomes for targeted delivery to E-selectin over-expressing tumor
      necrosis factor-alpha (TNF-alpha) activated endothelial cells. Liposomes composed
      of 1,2-dipalmitoyl-sn-glycero-3.;hosphocholine (DPPC), Cholesterol, and 1,2
      Distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000]
      maleimide (DSPE-PEG-Mal) were loaded with rapamycin via lipid film hydration,
      after which they were further functionalized by coupling N-succinimidyl-S
      acetylthioacetate (SATA)-modified mouse anti human E-selectin antibodies to the
      distal ends of the maleimidyl (Mal)-PEG groups. In cell binding assays, these
      immunoliposomes bound specifically to TNF-alpha activated endothelial cells. Upon
      internalization, rapamycin loaded immunoliposomes inhibited proliferation and
      migration of endothelial cells, as well as expression of inflammatory mediators.
      Our findings demonstrate that rapamycin-loaded immunoliposomes can specifically
      inhibit inflammatory responses in inflamed endothelial cells.

PMID- 29038065
TI  - Cationic nanoemulsions as nucleic acids delivery systems.
AB  - Since the first clinical studies, knowledge in the field of gene therapy has
      advanced significantly, and these advances led to the development and subsequent
      approval of the first gene medicines. Although viral vectors-based products offer
      efficient gene expression, problems related to their safety and immune response
      have limited their clinical use. Thus, design and optimization of nonviral
      vectors is presented as a promising strategy in this scenario. Nonviral systems
      are nanotechnology-based products composed of polymers or lipids, which are
      usually biodegradable and biocompatible. Cationic liposomes are the most studied
      nonviral carriers and knowledge about these systems has greatly evolved,
      especially in understanding the role of phospholipids and cationic lipids.
      However, the search for efficient delivery systems aiming at gene therapy remains
      a challenge. In this context, cationic nanoemulsions have proved to be an
      interesting approach, as their ability to protect and efficiently deliver nucleic
      acids for diverse therapeutic applications has been demonstrated. This review
      focused on cationic nanoemulsions designed for gene therapy, providing an
      overview on their composition, physicochemical properties, and their efficacy on
      biological response in vitro and in vivo.

PMID- 29038067
TI  - Clay minerals: Properties and applications to dermocosmetic products and
      perspectives of natural raw materials for therapeutic purposes-A review.
AB  - Clay minerals are layered materials with a number of peculiar properties, which
      find many relevant applications in various industries. Since they are easily
      found everywhere, they are particularly attractive due to their economic
      viability. In the cosmetic industry, clay minerals are often used as excipients
      to stabilize emulsions or suspensions and to modify the rheological behavior of
      these systems. They also play an important role as adsorbents or absorbents, not
      only in cosmetics but also in other industries, such as pharmaceuticals. This
      reviewer believes that since this manuscript is presented as covering topical
      applications that include pharmaceuticals, some types of clay minerals should be
      considered as a potential material to be used as drug delivery systems. We review
      several applications of clay minerals to dermocosmetic products, relating them to
      the underlying properties of these materials and exemplifying with a number of
      clay minerals available in the market. We also discuss the use of clay minerals
      in topically-applied products for therapeutic purposes, specially for skin
      treatment and protection.

PMID- 29038066
TI  - In vitro and preclinical assessment of an intranasal spray formulation of
      parathyroid hormone PTH 1-34 for the treatment of osteoporosis.
AB  - Osteoporosis treatment with PTH 1-34 injections significantly reduces the
      incidence of bone fracture. Potential further reductions in fracture rate should
      be observed through nasal spray delivery to address the poor compliance
      associated with patient dislike of repeated PTH 1-34 subcutaneous injections. In
      vitro human osteoblast-like Saos-2 cell intracellular cAMP levels were used to
      define PTH 1-34 nasal spray formulation bioactivity. The chemically synthesised
      PTH 1-34 had an EC50 of 0.76nM. Absorption enhancers polyethylene glycol (15)
      hydroxystearate (Solutol(r) HS15), poloxamer 407, chitosan or sodium hyaluronate
      did not diminish the bioactivity of PTH 1-34 within an in vitro cell culture
      model (p >0.05). We also demonstrated the effectiveness of the transmucosal
      absorption enhancer Solutol(r) HS15 in a nasal spray formulation using a
      preclinical pharmacokinetic model. In Sprague-Dawley rats without the absorption
      enhancer the uptake of PTH 1-34 into the blood via intranasal delivery produced a
      Cmax of 2.1+/-0.5ng/ml compared to 13.7+/-1.6ng/ml with Solutol(r) HS15 enhancer
      (p=0.016) and a Cmax14.8+/-8ng/ml in subcutaneous injections. Together these data
      illustrate that the nasal spray formulation bioactivity in vitro is not affected
      by the nasal spray absorption enhancers investigated, and the Solutol(r) HS15
      nasal spray formulation had an equivalent pharmacokinetic profile to subcutaneous
      injection in the rat model. The Solutol(r) HS15 formulation therefore
      demonstrated potential as a PTH 1-34 nasal spray formulation for the treatment of
      osteoporosis.

PMID- 29038068
TI  - Polymeric microspheres for the sustained release of a protein-based drug carrier
      targeting the PDGFbeta-receptor in the fibrotic kidney.
AB  - Injectable sustained release drug delivery systems are an attractive alternative
      for the intravenous delivery of therapeutic proteins. In particular, for chronic
      diseases such as fibrosis, this approach could improve therapy by reducing the
      administration frequency while avoiding large variations in plasma levels. In
      fibrotic tissues the platelet-derived growth factor receptor beta (PDGFbetaR) is
      highly upregulated, which provides a target for site-specific delivery of drugs.
      Our aim was to develop an injectable sustained release formulation for the
      subcutaneous delivery of the PDGFbetaR-targeted drug carrier protein pPB-HSA,
      which is composed of multiple PDGFbetaR-recognizing moieties (pPB) attached to
      human serum albumin (HSA). We used blends of biodegradable multi-block copolymers
      with different swelling degree to optimize the release rate using the model
      protein HSA from microspheres produced via a water-in-oil-in-water double
      emulsion evaporation process. The optimized formulation containing pPB-HSA,
      showed complete release in vitro within 14days. After subcutaneous administration
      to mice suffering from renal fibrosis pPB-HSA was released from the microspheres
      and distributed into plasma for at least 7days after administration. Furthermore,
      we demonstrated an enhanced accumulation of pPB-HSA in the fibrotic kidney.
      Altogether, we show that subcutaneously administered polymeric microspheres
      present a suitable sustained release drug delivery system for the controlled
      systemic delivery for proteins such as pPB-HSA.

PMID- 29038069
TI  - Study protocol and rationale for a randomized double-blinded crossover trial of
      phentermine-topiramate ER versus placebo to treat binge eating disorder and
      bulimia nervosa.
AB  - INTRODUCTION: Bulimia nervosa (BN) and binge eating disorder (BED) are associated
      with severe psychological and medical consequences. Current therapies are
      limited, leaving up to 50% of patients symptomatic despite treatment,
      underscoring the need for additional treatment options. Qsymia, an FDA-approved
      medication for obesity, combines phentermine and topiramate ER. Topiramate has
      demonstrated efficacy for both BED and BN, but limited tolerability. Phentermine
      is FDA-approved for weight loss. A rationale for combined phentermine/topiramate
      for BED and BN is improved tolerability and efficacy. While a prior case series
      exploring Qsymia for BED showed promise, randomized studies are needed to
      evaluate Qsymia's safety and efficacy when re-purposed in eating disorders. We
      present a study protocol for a Phase I/IIa single-center, prospective, double
      blinded, randomized, crossover trial examining safety and preliminary efficacy of
      Qsymia for BED and BN. METHODS: Adults with BED (n=15) or BN (n=15) are
      randomized 1:1 to receive 12weeks Qsymia (phentermine/topiramate ER, 3.75mg/23mg
      15mg/92mg) or placebo, followed by 2-weeks washout and 12-weeks crossover, where
      those on Qsymia receive placebo and vice versa. Subsequently participants receive
      8weeks follow-up off study medications. The primary outcome is the number of
      binge days/week measured by EDE. Secondary outcomes include average number of
      binge episodes, percentage abstinence from binge eating, and changes in
      weight/vitals, eating psychopathology, and mood. DISCUSSION: To our knowledge
      this is the first randomized, double-blind protocol investigating the safety and
      efficacy of phentermine/topiramate in BED and BN. We highlight the background and
      rationale for this study, including the advantages of a crossover design. TRIAL
      REGISTRATION: Clinicaltrials.gov identifier NCT02553824 registered on 9/17/2015.
      https://clinicaltrials.gov/ct2/show/NCT02553824.

PMID- 29038070
TI  - Exploring young women's decisional needs for contraceptive method choice: a
      qualitative study.
AB  - OBJECTIVE: Assisting women with choosing contraceptive methods that meet their
      needs and preferences is essential to providing patient-centered care, but
      research to inform interventions supporting method choice is lacking. An
      assessment of patient decisional needs for contraceptive method choice may
      provide insight into patient-centered ways to support decision making. STUDY
      DESIGN: Using the Ottawa Decision Support Framework as a guide, we conducted a
      qualitative study with semistructured interviews to identify women's decisional
      needs for choosing a contraceptive method. The sample consisted of 21 women aged
      18-29 from an integrated health care delivery system. We employed thematic
      analysis to identify common themes in the participants' experience. RESULTS:
      Overall, participants perceived choosing a contraceptive method to be a somewhat
      difficult decision and described feeling hesitant and unsure. Lack of knowledge
      of and familiarity with methods and the unpredictability of side effects
      contributed to participants' hesitancy. Women considered method choice in the
      context of their lives and their values for various contraceptive attributes,
      particularly side effects. Participants identified several sources for
      contraceptive information. Information from friends and family was highly
      influential. Participants desired both factual and experiential information.
      CONCLUSIONS: Contraceptive method choice may be difficult for many young women,
      suggesting a need for decision support. Interventions supporting method choice
      may be more relevant if they directly address knowledge gaps and uncertainty as
      well as provide both factual and experiential information on a comprehensive set
      of contraceptive attributes.

PMID- 29038071
TI  - Contraceptive method use in the United States: trends and characteristics between
      2008, 2012 and 2014.
AB  - OBJECTIVE: The objective was to examine levels of, correlates of and changes in
      the use of individual and grouped methods of contraception among US females aged
      15-44 from 2008 to 2014. STUDY DESIGN: Using three rounds of the National Survey
      of Family Growth, we analyzed samples of 12,279 (2008), 5601 (2012) and 5699
      (2014) females. We conducted simple and multivariable logistic regression
      analyses to identify associations between demographic characteristics and
      contraceptive use, as well as between characteristics and changes in use
      patterns. RESULTS: In terms of overall trends in contraceptive use between 2008
      and 2014, there was no significant change in the proportion of women who used a
      method among either all women (60%) or those at risk of unintended pregnancy
      (90%). Significant changes in use occurred among six methods. The largest
      increase in use was among users of long-acting reversible contraceptive (LARC)
      methods, including the intrauterine device and implant - from 6% to 14% - across
      almost all population groups of female contraceptive users, while the largest
      decrease occurred among users of sterilization - from 37% to 28% - with lower
      income women driving the decline in female sterilization and higher-income women
      driving the decline in a partner's sterilization as a primary method. Moderate
      increases were seen in the use of withdrawal and natural family planning.
      CONCLUSION: Most shifts in recent contraceptive use have occurred among the most
      effective methods - sterilization and LARCs. Differences in method-specific user
      characteristics underscore the importance of ensuring full access to the broad
      range of methods available. IMPLICATIONS: The lack of change in the overall use
      of contraceptives among women at risk for unintended pregnancy may have
      implications for the extent to which further declines in national rates of
      unintended pregnancy can be expected.

PMID- 29038072
TI  - Amenorrhea rates and predictors during 1 year of levonorgestrel 52 mg
      intrauterine system use.
AB  - OBJECTIVE: The objective was to evaluate amenorrhea patterns and predictors of
      amenorrhea during the first year after levonorgestrel 52 mg intrauterine system
      (IUS) placement. STUDY DESIGN: This cohort analysis includes 1714 nulliparous and
      parous women who received a Liletta(r) levonorgestrel 52 mg IUS in a multicenter
      trial to evaluate efficacy and safety for up to 8 years. Participants maintained
      a daily diary with bleeding information. We assessed bleeding patterns in 90-day
      intervals; amenorrhea was defined as no bleeding or spotting in the preceding 90
      days. We employed multivariable regression to identify predictors of amenorrhea
      at 12 months. The predictor analysis only included women not using a
      levonorgestrel IUS in the month prior to study enrollment. RESULTS: In the month
      before enrollment, 148 and 1566 women, respectively, had used and not used a
      levonorgestrel IUS. Prior users averaged 50+/-19 months of use before IUS
      placement; 38.4% of these women reported amenorrhea at 12 months. Amenorrhea
      rates for non-prior-users at 3, 6, 9 and 12 months were 0.2%, 9.1%, 17.2% and
      16.9%, respectively. During the first 12 months, 29 (1.7%) women discontinued for
      bleeding irregularities; no women discontinued for amenorrhea. The only
      significant predictor of amenorrhea at 12 months was self-reported baseline
      duration of menstrual flow of fewer than 7 days vs. 7 or more days (18.2% vs.
      5.2%, adjusted odds ratio 3.70 [1.69, 8.07]). We found no relationships between
      12-month amenorrhea rates and age, parity, race, body mass index, baseline flow
      intensity or hormonal contraception use immediately prior to IUS placement.
      CONCLUSIONS: Amenorrhea rates during the first year of levonorgestrel 52 mg IUS
      use are similar at 9 and 12 months. Amenorrhea at 12 months is most common among
      women with shorter baseline duration of menstrual flow. IMPLICATIONS STATEMENT:
      This information provides more data for clinicians when counseling women about
      amenorrhea expectations, especially since women seeking a levonorgestrel 52 mg
      IUS for contraception are different than women desiring treatment for heavy
      menstrual bleeding. Amenorrhea at 12 months is most common among women with
      shorter baseline duration of menstrual flow.

PMID- 29038073
TI  - Protective role of metallothionein during regeneration in Eisenia andrei exposed
      to cadmium.
AB  - Lumbricid earthworms are often exposed to simultaneous action of various
      environmental stressors like soil contamination, temperature fluctuation or
      predators' attacks, which may induce extrusion of coelomocyte-containing coelomic
      fluid or loss of tail segments. If the injuries are not lethal, renewal of the
      immune-competent cells and soluble components of coelomic fluid and/or the
      regeneration of tail segments occurs. The aim of our investigations was to test
      the hypothesis that exposure of adult earthworms Eisenia andrei to cadmium
      polluted soil at room temperature (RT) and/or low temperature (6 degrees C) have
      adverse effects on restoration of experimentally depleted coelomocytes or on
      regeneration of amputated posterior segments. Intact control earthworms and their
      experimental counterparts subjected to electrostimulation-induced coelomocyte
      depletion or surgical amputation of posterior segments were maintained either in
      control soil or in soil spiked with cadmium chloride (500mg/kg air-dried soil) at
      RT or 6 degrees C. Four weeks after the beginning of experiments, cadmium
      accumulation in earthworm bodies was significantly lower at 6 degrees C than at
      room temperature. The numbers of restored cells and fluorophore contents were
      hardly affected by temperature or cadmium. However, cocoon production was reduced
      by cadmium and completely abolished at 6 degrees C and regeneration of amputated
      posterior segments was inhibited in cold but was enhanced by cadmium exposure at
      RT. Independently on the temperature, the 4-week cadmium exposure of adult
      earthworms was connected with significantly upregulated expression of Cd
      metallothionein (but not of catalase, lysenin and phytochelatin) in coelomocytes.

PMID- 29038074
TI  - Insights from pharmacological similarity of epigenetic targets in
      epipolypharmacology.
AB  - As the number of compounds tested against epigenetic targets grows, exploration
      of the possible associations in chemical space among these targets could lead to
      the identification of new drugs or new designs of epipolypharmacological
      molecules. Thus, here we review compound-epitarget associations of public
      databases. Specifically, we explore the structure-multitarget activity
      relationships and diversity of over 7000 compounds tested against 52 epigenetic
      related targets. We found that, whereas inhibitors of histone deacetylases and
      other epigenetic targets are clustered in the chemical space, the chemical space
      of inhibitors of different DNA methyltransferases (DNMTs) did not overlap,
      indicating DNMT selectivity. These and other compound-epitarget relationships
      discussed here could be useful for both drug repurposing and the rational design
      of epipolypharmacological compounds.

PMID- 29038076
TI  - Editorial on Special Issue: Animal models of Tourette syndrome.

PMID- 29038075
TI  - Biochemical marker discovery, testing and evaluation for facilitating OA drug
      discovery and development.
AB  - Osteoarthritis (OA) is the most common form of joint disease. This presents the
      OA research community and pharmaceutical companies developing disease-modifying
      OA drugs (DMOADs) with great opportunities. The different OA subtypes complicate
      the traditional approaches for developing new treatments. If we can identify new
      markers that can distinguish different subtypes this could greatly facilitate
      drug development from early discovery to late clinical development. Nevertheless,
      the current approaches result in poorly targeted treatments and the inability to
      recruit the right patients for clinical trials. Thus, there is an urgent medical
      need for objective biomarker tools for patient phenotyping.

PMID- 29038077
TI  - The Effects of Red Blood Cell Transfusion on Functional Outcome after Aneurysmal
      Subarachnoid Hemorrhage.
AB  - BACKGROUND: The optimal red blood cell transfusion (RBCT) trigger for patients
      with aneurysmal subarachnoid hemorrhage (SAH) is unknown. In patients with
      cerebral vasospasm, anemia may increase susceptibility to ischemic injury;
      conversely, RBCT may worsen outcome given known deleterious effects. OBJECTIVE:
      To examine the association between RBCT, delayed cerebral ischemia (DCI),
      vasospasm, and outcome after SAH. METHODS: A total of 421 consecutive patients
      with SAH, admitted to a neurocritical care unit at a university-affiliated
      hospital and who underwent surgical occlusion of their ruptured aneurysm were
      retrospectively identified from a prospective observational database. Propensity
      score methods were used to reduce the bias associated with treatment selection.
      RESULTS: Two hundred and sixty-one patients (62.0%) received an RBCT.
      Angiographic vasospasm (odds ratio [OR] 1.6; 95% confidence interval [CI], 1.1
      2.3; P = 0.025) but not severe angiographic spasm, DCI, or delayed infarction was
      associated with RBCT. A total of 283 patients (67.2%) experienced a favorable
      outcome, defined as good or moderately disabled on the Glasgow Outcome Scale; 47
      (11.2%) were severely disabled or vegetative and 91 patients (21.6%) were dead at
      6-month follow-up. Among patients who survived >=2 days, RBCT was associated with
      unfavorable outcome (OR, 2.6; 95% CI, 1.6-4.1). Transfusion of >=3 units of blood
      was associated with an increased incidence of unfavorable outcome. Propensity
      analysis to control for the probability of exposure to RBCT conditional on
      observed covariates measured before RBCT indicates that RBCT is associated with
      unfavorable outcome in the absence of DCI (OR, 2.17; 95% CI, 1.56-3.01; P <
      0.0001) but not when DCI is present (OR, 0.82; 95% CI, 0.35-1.92; P = 0.65).
      CONCLUSIONS: Blood transfusions are associated with unfavorable outcome after SAH
      particularly when DCI is absent. Propensity analysis suggests that RBCT may be
      associated with poor outcome rather than being a marker of disease severity.
      However, when DCI is present, RBCT may help improve outcome.

PMID- 29038078
TI  - Predictors of Postoperative Recovery Based on Health-Related Quality of Life in
      Patients after Degenerative Lumbar Scoliosis Surgery.
AB  - OBJECTIVE: To investigate the factors associated with the recovery process of
      elderly patients after degenerative lumbar scoliosis surgery. METHODS: A total of
      213 elderly patients who had undergone surgical treatment for degenerative lumbar
      scoliosis from 2011 to 2015 were included retrospectively in this study. Clinical
      data and demographics were collected for logistic regression analysis. RESULTS:
      Among 213 eligible patients, 77 (38.5%) were classified as being in the excellent
      group, 70 (35%) as showing improvement, 24 (12%) as showing no change, and 29
      (14.5%) as having deteriorated. At baseline, patients differed significantly from
      matched normative data in all Scoliosis Research Society domains. Larger
      differences from normative values were found for pain and activity domains. After
      surgery, each domain improved significantly. In the multivariate logistic
      regression, age 60-70 years (odds ratio [OR], 2.431; 95% confidence interval
      [CI], 1.143-5.174), and American Society of Anesthesiologists grade <3 (OR,
      2.987; 95% CI, 1.519-5.874) may be predictive factors for a satisfying recovery,
      whereas presence of complications (OR, 0.342; 95% CI, 0.153-0.765), fusion to the
      sacrum (OR, 0.200; 95% CI, 0.076-0.523), and more osteotomies (OR, 0.360; 95% CI,
      0.132-0.985) have negative effects on the recovery process. CONCLUSIONS: The
      factors that affect postoperative recovery in elderly patients with degenerative
      lumbar scoliosis are age, American Society of Anesthesiologists grade, distal
      fusion level, presence of complications, and number of osteotomies.

PMID- 29038079
TI  - Optical Coherence Tomography in the Management of Skull Base Fibrous Dysplasia
      with Optic Nerve Involvement.
AB  - BACKGROUND: Fibrous dysplasia (FD) of the skull base can manifest with optic
      nerve compression. As most patients initially do not experience vision loss,
      controversy exists whether to proceed with prophylactic surgical decompression or
      elect for conservative observation. Optical coherence tomography (OCT), a
      physiologic imaging modality widely used to assess the condition of the retinal
      nerve fiber layer (RNFL), has been useful in monitoring compressive tumors on the
      optic nerve. This study evaluated potential use of OCT in management of patients
      with fibrous dysplasia and optic nerve involvement. METHODS: Six patients with
      suspected optic nerve compression who underwent OCT imaging as part of a neuro
      ophthalmic examination were reviewed over a 2-year period. Patient records were
      evaluated for visual examination measures, most notably the presence of optic
      neuropathy, and radiographic measures on computed tomography. Measures were
      compared by age-adjusted RNFL thickness (above or below fifth percentile) on OCT
      imaging. RESULTS: Two patients were found to have mild optic neuropathy in 1 eye
      each. Three of 12 eyes fell below the age-adjusted fifth percentile of RNFL
      thickness. Presence of optic neuropathy was associated with abnormal age-adjusted
      RNFL thickness but not with optic nerve compression (P = 0.45). CONCLUSIONS:
      Abnormal RNFL thickness as measured by OCT better predicted the presence of optic
      neuropathy than computed tomography alone. OCT may be a valuable imaging modality
      to monitor patients with fibrous dysplasia for development of optic neuropathy
      during periods of conservative watchful waiting.

PMID- 29038080
TI  - A Stent-Retrieving into an Aspiration Catheter with Proximal Balloon (ASAP)
      Technique: A Technique of Mechanical Thrombectomy.
AB  - OBJECTIVE: The best technique for the first attempt at mechanical thrombectomy
      for acute ischemic stroke is a still matter of debate. In this study, we evaluate
      the efficacy of a stent-retrieving into an aspiration catheter with proximal
      balloon (ASAP) technique that uses a series of thrombus extraction by withdrawing
      the stent retriever into the aspiration catheter and continuous aspiration from
      the aspiration catheter at the first attempt. METHODS: We performed a
      retrospective analysis of 42 consecutive patients with acute ischemic stroke
      caused by occlusions in the anterior circulation who were treated with the ASAP
      technique at our institution. Preoperative patient characteristic, including age,
      thrombus location, Alberta Stroke Program Early CT Score, National Institutions
      of Health Stroke Scale, and time from onset to puncture; postoperative
      Thrombolysis in Cerebral Infarction score; modified Rankin Scale score after 3
      months; time from puncture to recanalization; the number of passes to achieve
      recanalization; and procedural complications, including intracranial hemorrhage,
      embolization to new territory, and distal embolization, were assessed. RESULTS: A
      Thrombolysis in Cerebral Infarction score of 2B or 3 was achieved in 40/42
      patients (95.2%). Average time from puncture to the final recanalization was 21.5
      minutes. Recanalization was achieved in a single attempt in 31 patients (77.5%).
      Embolization to new territory was observed in only 2 patients (4.8%); no patient
      developed distal embolization or intracranial hemorrhage including asymptomatic
      subarachnoid hemorrhage. Thirty-two patients (76.2%) achieved modified Rankin
      Scale scores of 0-2 at 3 months postoperatively. CONCLUSIONS: Our ASAP technique
      showed fast recanalization, minimal complications, and good clinical outcomes in
      this case series.

PMID- 29038081
TI  - Progressive Functional Underdrainage in Cerebrospinal Fluid Shunt-Dependent Women
      During Pregnancy: Case Report and Review of the Literature.
AB  - BACKGROUND: Since the 1950s cerebrospinal fluid (CSF) shunt dependency has no
      longer been a contradiction to normal life, including sexuality and pregnancy in
      women, because of advances in the understanding of hydrocephalus and shunt
      technology. Although pregnancy in shunt-dependent women is rare, it causes
      uncertainty among treating physicians. CASE DESCRIPTION: We report the case of a
      34-year-old pregnant woman with a ventriculoperitoneal shunt. Throughout her
      pregnancy she experienced progressive symptoms of CSF underdrainage without any
      signs of other pregnancy-related complications. After the delivery of a healthy
      infant, shunt resistance had to be readjusted to prepregnancy levels. A
      comprehensive review of the literature reports in English, listed in PubMed, is
      provided. CONCLUSIONS: Conservative treatment of pregnancy-related functional
      underdrainage by consecutive valve pressure adjustment is possible, easy, and
      safe.

PMID- 29038082
TI  - Supraorbital Approach for Resection of Clinoidal Meningioma.
AB  - Meningiomas of the clinoid region pose a formidable surgical challenge. Pterional
      craniotomy is the traditional approach and is often associated with high-risk
      postsurgical morbidities. In the current presentation, we describe an elderly
      male with a clinoidal meningioma who underwent a minimally invasive supraorbital
      craniotomy for tumor resection. Patient presentation, neuroimaging, and surgical
      techniques (patient position, incision, anatomic consideration, and surgical
      steps) are described meticulously. Initial intraoperative steps include
      dissection via the corridor between the carotid artery and the tentorium, as well
      as exposing the tumor in the opticocarotid triangle, followed by tumor dissection
      using microsurgical techniques. Care must be taken to preserve the supraorbital
      nerve to prevent frontal numbness and avoid violation of the frontal sinus to
      prevent postoperative cerebrospinal fluid leak. Emphasis on using this minimally
      invasive procedure for clinoidal meningiomas over the pterional approach for a
      select cohort of patients is laid, considering the cosmetic merits and adequate
      extent of tumor resection.

PMID- 29038083
TI  - Reversible Parkinson-Like Symptoms in Patient with Bilateral Chronic Subdural
      Hematomas and Cervical Spinal Stenosis.
AB  - BACKGROUND: Gait abnormalities have been seen in patients with Parkinson disease
      or Parkinson-like (P-L) disorders and cervical spinal stenosis. Acute
      presentation of P-L symptoms has been reported in 24 cases caused by chronic
      subdural hematomas with 11 cases due to bilateral chronic subdural hematomas.
      When a patient also presents with cervical spinal stenosis, the correct
      therapeutic decision between P-L disorders and myelopathy is challenging. CASE
      DESCRIPTION: An 80-year-old male presented with a 2-week history of weakness in
      his left leg. A few days before presentation, his gait had deteriorated quite
      dramatically. Neurologic examination showed mild leg weakness, hyperreflexia, and
      a gait that was slow and wide based, at times festinating but with relatively
      spared arm movement. He also had masked facial features with increased tone in
      his extremities. Magnetic resonance imaging of the cervical spine showed cervical
      stenosis at C5-6, and computed tomography of the head showed large bilateral
      subdural hematomas. The subdural hematomas were drained. Immediate improvement in
      his symptoms was observed with complete resolution by his third month of follow
      up. The patient never had a history of Parkinson disease. CONCLUSIONS: This paper
      reports for the first time a patient who presented with acute P-L symptoms and
      cervical myelopathy with findings of both bilateral chronic subdural hematomas
      and cervical spinal stenosis. The decision to drain the subdural hematoma in our
      case resulted in full recovery of the patient's gait and other extrapyramidal
      symptoms. This paper reviews the literature on reversible P-L symptoms caused by
      bilateral chronic subdural hematomas.

PMID- 29038084
TI  - Management of Through-and-Through Penetrating Skull Injury: A Railroad Spike That
      Transgressed the Anterior Skull Base.
AB  - BACKGROUND: Penetrating injuries involving foreign objects that transgress the
      entirety of the human skull present challenges in the management of vascular
      injuries, infectious risk, cerebrospinal fluid leak, and cosmetic repair.
      Ultimately, effective management of these injuries requires a multidisciplinary
      team and judicious surgical planning. CASE DESCRIPTION: Here we present the
      treatment of a patient who experienced a penetrating injury from a railroad
      spike, with entry and exit points involving the left and right anterior aspects
      of the temporal fossa, respectively. CONCLUSIONS: The rationale for management
      decisions is reviewed in the context of the published literature.

PMID- 29038085
TI  - Outcomes of Two-Isocenter Gamma Knife Radiosurgery for Patients with Typical
      Trigeminal Neuralgia: Pain Response and Quality of Life.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of 2-isocenter Gamma Knife
      surgery (GKS) by reviewing patients with trigeminal neuralgia (TN) from the last
      10 years. METHODS: A total of 247 patients were followed up and the Barrow
      Neurological Institute scale was used to evaluate pain degree. Patients' age,
      gender, pain duration and location, preoperative/postoperative Barrow
      Neurological Institute scale score, time to initial pain relief, recurrence time,
      and complications were documented and analyzed. RESULTS: Patients who underwent a
      2-isocenter GKS achieved earlier initial pain relief. The median time of initial
      pain relief was 2.0 months. Kaplan-Meier analysis showed that the patients with a
      shorter history of TN and the patients without preoperative surgery achieved
      earlier initial pain relief. During the 122.8 months of follow-up, the median
      time of recurrence-free pain relief was 49.7 months. Age was found to be a risk
      factor of recurrence. Patients who underwent 2-isocenter GKS had a higher rate of
      postoperative facial numbness, but only 9 cases reported bothersome facial
      numbness. Multibranch involvement was a risk factor for postoperative facial
      numbness. CONCLUSIONS: Compared with other modalities, 2-isocenter GKS was a safe
      and highly effective option for patients with TN. However, more data need to be
      collected to verify its long-term effect.

PMID- 29038087
TI  - Integrons in Enterobacteriaceae: diversity, distribution and epidemiology.
AB  - Integrons are versatile gene acquisition systems that allow efficient capturing
      of exogenous genes and ensure their expression. Various classes of integrons
      possessing a wide variety of gene cassettes are ubiquitously distributed in
      enteric bacteria worldwide. The epidemiology of integrons associated multidrug
      resistance in Enterobacteriaceae is rapidly evolving. In the past two decades,
      the incidence of integrons in enteric bacteria has increased drastically with
      evolution of multiple gene cassettes, novel gene arrangements and complex
      chromosomal integrons such as Salmonella genomic islands. This review focuses on
      the distribution, versatility, spread and global trends of integrons among
      important members of the Enterobacteriaceae, including Escherichia coli,
      Klebsiella, Shigella and Salmonella, which are known to cause infections
      globally. Such a comprehensive understanding of integron-associated antibiotic
      resistance, their role in the spread of such resistance traits and their clinical
      relevance especially with regard to each genus individually is paramount to
      contain the global spread of antibiotic resistance.

PMID- 29038086
TI  - Radiosurgery for Treatment of Renal Cell Metastases to Spine: A Systematic Review
      of the Literature.
AB  - BACKGROUND: The incidence of renal cell carcinoma (RCC) continues to increase,
      and the spine is the most common site for bony metastasis. Radiation therapy is
      one treatment for spinal RCC metastasis. Stereotactic body radiotherapy (SBRT) is
      a newer treatment that reportedly has benefits over conventional external beam
      radiotherapy. This study systematically reviewed the current literature on SBRT
      for metastatic RCC to spine. METHODS: A search of PubMed, Embase, and Scopus
      databases was conducted in accordance with PRISMA (Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses) guidelines. Clinical articles evaluating
      SBRT for RCC metastases were identified. After inclusion and exclusion criteria
      were applied, the search resulted in 9 articles. Data including pain outcomes,
      local control, survival outcomes, vertebral compression fracture (VCF), and
      toxicity were extracted and evaluated. RESULTS: The studies analyzed showed an
      improvement in pain in 41%-95% of patients. Local control rates after SBRT ranged
      71.2%-85.7% at 1 year, a significant improvement when compared with conventional
      external beam radiotherapy. The rate of VCF after treatment with SBRT ranged 16%
      27.5%, with single-fraction therapy being a risk factor for increased incidence.
      Overall toxicity rates ranged 23%-38.5%, with only 3 cases of grade 3 toxicity
      (nausea) and no cases of radiation myelitis. CONCLUSIONS: Use of SBRT for spinal
      metastasis from RCC resulted in significant local control and pain outcomes.
      There is a risk of VCF with SBRT; however, treatment seems to be well tolerated
      with few serious side effects. There is continued need for long-term prospective
      studies investigating the optimal role of SBRT in the treatment algorithm of RCC
      spinal metastases.

PMID- 29038088
TI  - First description of rpsJ and mepA mutations associated with tigecycline
      resistance in Staphylococcus aureus isolated from a cystic fibrosis patient
      during antibiotic therapy.

PMID- 29038089
TI  - Time course and interrelationship of dysrhythmias in patients with surgically
      repaired atrial septal defect.
AB  - BACKGROUND: Atrial fibrillation (AF) and other supraventricular tachycardias
      (SVTs) are known complications after surgical repair of atrial septal defect
      (ASD), but sinus node dysfunction (SND) and complete atrioventricular conduction
      block (cAVB) may also occur. OBJECTIVE: The aim of this study was to examine time
      course and interrelationship of various dysrhythmias in patients with ASD.
      METHODS: Adult patients (N = 95) with surgically repaired secundum ASD (n = 40),
      partial atrioventricular septal defect (n = 37) or sinus venosus defect (n = 18),
      and documented SND, cAVB, AF, and/or other SVT were included. The median age at
      repair was 13 years (interquartile range [IQR] 6-45 years), and patients were
      followed for 26 years (IQR 15-37 years) after ASD repair. RESULTS: SND was
      observed in 34 patients (36%), cAVB in 14 (14%), AF in 48 (49%), and SVT in 44
      (45%); 37 patients (39%) had >=2 dysrhythmias. All dysrhythmias presented most
      often after ASD repair (P < .01), with a median duration of 12 years (IQR 17 days
      - 32 years) to 16 years (IQR 4 - 28 years) between repair and onset. Development
      of SND and cAVB late after ASD repair was not related to a redo procedure in 100%
      and 60% of patients, respectively. SND preceded atrial tachyarrhythmias in 50% (P
      = .31) and SVT preceded AF in 68% (P = .09) of patients with both dysrhythmias.
      CONCLUSION: A substantial number of dysrhythmias presented (very) late after ASD
      repair. In most patients, development of late SND and cAVB was not related to
      redo procedures. In patients with multiple dysrhythmias, a specific order of
      appearance was not observed.

PMID- 29038090
TI  - Variation in DNA-Damage Responses to an Inhalational Carcinogen (1,3-Butadiene)
      in Relation to Strain-Specific Differences in Chromatin Accessibility and Gene
      Transcription Profiles in C57BL/6J and CAST/EiJ Mice.
AB  - BACKGROUND: The damaging effects of exposure to environmental toxicants
      differentially affect genetically distinct individuals, but the mechanisms
      contributing to these differences are poorly understood. Genetic variation
      affects the establishment of the gene regulatory landscape and thus gene
      expression, and we hypothesized that this contributes to the observed
      heterogeneity in individual responses to exogenous cellular insults. OBJECTIVES:
      We performed an in vivo study of how genetic variation and chromatin organization
      may dictate susceptibility to DNA damage, and influence the cellular response to
      such damage, caused by an environmental toxicant. MATERIALS AND METHODS: We
      measured DNA damage, messenger RNA (mRNA) and microRNA (miRNA) expression, and
      genome-wide chromatin accessibility in lung tissue from two genetically divergent
      inbred mouse strains, C57BL/6J and CAST/EiJ, both in unexposed mice and in mice
      exposed to a model DNA-damaging chemical, 1,3-butadiene. RESULTS: Our results
      showed that unexposed CAST/EiJ and C57BL/6J mice have very different chromatin
      organization and transcription profiles in the lung. Importantly, in unexposed
      CAST/EiJ mice, which acquired relatively less 1,3-butadiene-induced DNA damage,
      we observed increased transcription and a more accessible chromatin landscape
      around genes involved in detoxification pathways. Upon chemical exposure,
      chromatin was significantly remodeled in the lung of C57BL/6J mice, a strain that
      acquired higher levels of 1,3-butadiene-induced DNA damage, around the same
      genes, ultimately resembling the molecular profile of CAST/EiJ. CONCLUSIONS:
      These results suggest that strain-specific changes in chromatin and transcription
      in response to chemical exposure lead to a "compensation" for underlying genetic
      driven interindividual differences in the baseline chromatin and transcriptional
      state. This work represents an example of how chemical and environmental
      exposures can be evaluated to better understand gene-by-environment interactions,
      and it demonstrates the important role of chromatin response in transcriptomic
      changes and, potentially, in deleterious effects of exposure.
      https://doi.org/10.1289/EHP1937.

PMID- 29038092
TI  - Implications of Attrition in a Longitudinal Web-Based Survey: An Examination of
      College Students Participating in a Tobacco Use Study.
AB  - BACKGROUND: Web-based survey research has several benefits, including low cost
      and burden, as well as high use of the Internet, particularly among young adults.
      In the context of longitudinal studies, attrition raises concerns regarding the
      validity of data, given the potential associations with individual and
      institutional characteristics, or the focal area of study (eg, cigarette use).
      OBJECTIVES: The objective of this study was to compare baseline characteristics
      of nonresponders versus responders in a sample of young adult college students in
      a Web-based longitudinal study regarding tobacco use. METHODS: We conducted a
      secondary data analysis of 3189 college students from seven Georgia colleges and
      universities in a 2-year longitudinal study. We examined baseline tobacco use, as
      well as individual- and institutional-level factors, as predictors of attrition
      between wave 1 (October and November 2014) and wave 2 (February and March 2015)
      using multilevel modeling. Results: A total 13.14% (419/3189) participants were
      lost to follow-up at wave 2. Predictors of nonresponse were similar in the models
      examining individual-level factors and institutional-level factors only and
      included being black versus white (odds ratio [OR] 1.74, CI 1.23-2.46); being
      male versus female (OR 1.41, CI 1.10-1.79); seeking a bachelor's degree versus
      advanced degree (OR 1.41, CI 1.09-1.83); not residing on campus (OR 0.62, CI 0.46
      0.84); past 30-day tobacco use (OR 1.41, CI 1.10-1.78); attending a nonprivate
      college (OR 0.48, CI 0.33-0.71); and attending a college with <=10,000 students
      (OR 0.56, CI 0.43-0.73). CONCLUSIONS: Future longitudinal studies should assess
      predictors of attrition to examine how survey topic and other individual and
      institutional factors might influence the response to allow for correction of
      selection bias.

PMID- 29038091
TI  - Small-Scale Food Animal Production and Antimicrobial Resistance: Mountain,
      Molehill, or Something in-between?
AB  - SUMMARY: Small-scale food animal production is widely practiced around the globe,
      yet it is often overlooked in terms of the environmental health risks. Evidence
      suggests that small-scale food animal producers often employ the use of
      antimicrobials to improve the survival and growth of their animals, and that this
      practice leads to the development of antimicrobial resistance (AMR) that can
      potentially spread to humans. The nature of human-animal interactions in small
      scale food animal production systems, generally practiced in and around the home,
      likely augments spillover events of AMR into the community on a scale that is
      currently unrecognized and deserves greater attention.
      https://doi.org/10.1289/EHP2116.

PMID- 29038093
TI  - Patient Portal Use and Experience Among Older Adults: Systematic Review.
AB  - BACKGROUND: The older adult population (65 years or older) in the United States
      is growing, and it is important for communities to consider ways to support the
      aging population. Patient portals and electronic personal health records (ePHRs)
      are technologies that could better serve populations with the highest health care
      needs, such as older adults. OBJECTIVE: The aim of this study was to assess the
      existing research landscape related to patient portal and ePHR use and experience
      among older adults and to understand the benefits and barriers to older adults'
      use and adoption of patient portals and ePHRs. METHODS: We searched six pertinent
      bibliographic databases for papers, published from 2006 to 2016 and written in
      English, that focused on adults 60 years or older and their use of or experience
      with patient portals or ePHRs. We adapted preferred reporting items for
      systematic reviews and meta-analyses (PRISMA) guidelines to review papers based
      on exclusion and inclusion criteria. We then applied thematic analysis to
      identify key themes around use, experience, and adoption. RESULTS: We retrieved
      199 papers after an initial screening and removal of duplicate papers. Then we
      applied an inclusion and exclusion criteria, resulting in a final set of 17
      papers that focused on 15 separate projects. The majority of papers described
      studies involving qualitative research, including interviews and focus groups.
      They looked at the experience and use of ePHRs and patient portals. Overall, we
      found 2 main barriers to use: (1) privacy and security and (2) access to and
      ability to use technology and the Internet. We found 2 facilitators: (1)
      technical assistance and (2) family and provider advice. We also reported on
      older adults' experience, including satisfaction with the system and improvement
      of the quality of their health care. Several studies captured features that older
      adults wanted from these systems such as further assistance managing health
      related tasks and contextual health advice and tips. CONCLUSIONS: More research
      is needed to better understand the patient portal experience among older adults
      from initial use to adoption. There are also opportunities to explore the role of
      design in addressing barriers and supporting facilitators to patient portal and
      ePHR use. Finally, the future use of these systems by older adults should be
      anticipated and considered in the design process.

PMID- 29038094
TI  - Transdiagnostic, Psychodynamic Web-Based Self-Help Intervention Following
      Inpatient Psychotherapy: Results of a Feasibility Study and Randomized Controlled
      Trial.
AB  - BACKGROUND: Mental disorders have become a major health issue, and a substantial
      number of afflicted individuals do not get appropriate treatment. Web-based
      interventions are promising supplementary tools for improving health care for
      patients with mental disorders, as they can be delivered at low costs and used
      independently of time and location. Although psychodynamic treatments are used
      frequently in the face-to-face setting, there has been a paucity of studies on
      psychodynamic Web-based self-help interventions. OBJECTIVE: The objective of this
      study was to determine the feasibility and preliminary efficacy of a
      transdiagnostic affect-focused psychodynamic Web-based self-help intervention
      designed to increase emotional competence of patients with mental disorders.
      METHODS: A total of 82 psychotherapy inpatients with mixed diagnoses were
      randomized into two groups. Following discharge, the intervention group (IG) got
      access to a guided version of the intervention for 10 weeks. After a waiting
      period of 10 weeks, the wait-list control group (WLCG) got access to an unguided
      version of the intervention. We reported the assessments at the beginning (T0)
      and at the end of the intervention, resp. the waiting period (T1). The primary
      outcome was satisfaction with the treatment at T1. Secondary outcome measures
      included emotional competence, depression, anxiety, and quality of life.
      Statistical analyses were performed with descriptive statistics (primary outcome)
      and analysis of covariance; a repeated measurement analysis of variance was used
      for the secondary outcomes. Effect sizes were calculated using Cohen d and data
      were analyzed as per protocol, as well as intention-to-treat (ITT). RESULTS:
      Patients were chronically ill, diagnosed with multiple diagnoses, most frequently
      with depression (84%, 58/69), anxiety (68%, 47/69), personality disorder (38%,
      26/69), and depersonalization-derealization disorder (22%, 15/69). A majority of
      the patients (86%, 36/42) logged into the program, of which 86% (31/36) completed
      the first unit. Satisfaction with the units mastered was rated as good (52%,
      16/31) and very good (26%, 9/31). However, there was a steady decline of
      participation over the course of the program; only 36% of the participants
      (13/36) participated throughout the trial completing at least 50% of the
      sessions. According to the ITT analysis, participants improved statistically
      significantly and with moderate effect sizes (Cohen d) compared with the WLCG
      regarding depression (d=0.60), quality of life (d=0.53), and emotional competence
      (d=0.49). Effects were considerably stronger for the completers with respect to
      depression (d=1.33), quality of life (d=0.83), emotional competence (d=0.68), and
      general anxiety (d=0.62). CONCLUSIONS: Although overall program satisfaction and
      benefit of the program were favorable with respect to the indicators of emotional
      disorders, the rate of completion was low. Our findings point to the need to
      target the intervention more specifically to the needs and capabilities of
      participants and to the context of the intervention. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT02671929; https://clinicaltrials.gov/ct2/show/NCT02671929
      (Archived by WebCite at http://www.webcitation.org/6ntWg1yWb).

PMID- 29038095
TI  - Factors Associated With Engagement With a Web-Based Lifestyle Intervention
      Following Provision of Coronary Heart Disease Risk: Mixed Methods Study.
AB  - BACKGROUND: Web-based interventions provide the opportunity to combine the
      tailored approach of face-to-face interventions with the scalability and cost
      effectiveness of public health interventions. This potential is often limited by
      low engagement. A number of studies have described the characteristics of
      individuals who engage more in Web-based interventions but few have explored the
      reasons for these variations. OBJECTIVE: We aimed to explore individual-level
      factors associated with different degrees of engagement with a Web-based behavior
      change intervention following provision of coronary heart disease (CHD) risk
      information, and the barriers and facilitators to engagement. METHODS: This study
      involved the secondary analysis of data from the Information and Risk
      Modification Trial, a randomized controlled trial of a Web-based lifestyle
      intervention alone, or alongside information on estimated CHD risk. The
      intervention consisted of three interactive sessions, each lasting up to 60
      minutes, delivered at monthly intervals. Participants were characterized as high
      engagers if they completed all three sessions. Thematic analysis of qualitative
      data from interviews with 37 participants was combined with quantitative data on
      usage of the Web-based intervention using a mixed-methods matrix, and data on the
      views of the intervention itself were analyzed across all participants. RESULTS:
      Thirteen participants were characterized as low engagers and 24 as high engagers.
      There was no difference in age (P=.75), gender (P=.95), or level of risk (P=.65)
      between the groups. Low engagement was more often associated with: (1) reporting
      a negative emotional reaction in response to the risk score (P=.029), (2)
      perceiving that the intervention did not provide any new lifestyle information
      (P=.011), and (3) being less likely to have reported feeling an obligation to
      complete the intervention as part of the study (P=.019). The mixed-methods matrix
      suggested that there was also an association between low engagement and less
      success with previous behavior change attempts, but the statistical evidence for
      this association was weak (P=.16). No associations were seen between engagement
      and barriers or facilitators to health behavior change, or comments about the
      design of the intervention itself. The most commonly cited barriers related to
      issues with access to the intervention itself: either difficulties remembering
      the link to the site or passwords, a perceived lack of flexibility within the
      website, or lack of time. Facilitators included the nonjudgmental presentation of
      lifestyle information, the use of simple language, and the personalized nature of
      the intervention. CONCLUSIONS: This study shows that the level of engagement with
      a Web-based intervention following provision of CHD risk information is not
      influenced by the level of risk but by the individual's response to the risk
      information, their past experiences of behavior change, the extent to which they
      consider the lifestyle information helpful, and whether they felt obliged to
      complete the intervention as part of a research study. A number of facilitators
      and barriers to Web-based interventions were also identified, which should inform
      future interventions.

PMID- 29038096
TI  - Raising Awareness About Cervical Cancer Using Twitter: Content Analysis of the
      2015 #SmearForSmear Campaign.
AB  - BACKGROUND: Cervical cancer is the second most common cancer among women under 45
      years of age. To deal with the decrease of smear test coverage in the United
      Kingdom, a Twitter campaign called #SmearForSmear has been launched in 2015 for
      the European Cervical Cancer Prevention Week. Its aim was to encourage women to
      take a selfie showing their lipstick going over the edge and post it on Twitter
      with a raising awareness message promoting cervical cancer screening. The
      estimated audience was 500 million people. Other public health campaigns have
      been launched on social media such as Movember to encourage participation and
      self-engagement. Their result was unsatisfactory as their aim had been diluted to
      become mainly a social buzz. OBJECTIVE: The objectives of this study were to
      identify the tweets delivering a raising awareness message promoting cervical
      cancer screening (sensitizing tweets) and to understand the characteristics of
      Twitter users posting about this campaign. METHODS: We conducted a 3-step content
      analysis of the English tweets tagged #SmearForSmear posted on Twitter for the
      2015 European Cervical Cancer Prevention Week. Data were collected using the
      Twitter application programming interface. Their extraction was based on an
      analysis grid generated by 2 independent researchers using a thematic analysis,
      validated by a strong Cohen kappa coefficient. A total of 7 themes were coded for
      sensitizing tweets and 14 for Twitter users' status. Verbatims were thematically
      and then statistically analyzed. RESULTS: A total of 3019 tweets were collected
      and 1881 were analyzed. Moreover, 69.96% of tweets had been posted by people
      living in the United Kingdom. A total of 57.36% of users were women, and sex was
      unknown in 35.99% of cases. In addition, 54.44% of the users had posted at least
      one selfie with smeared lipstick. Furthermore, 32.32% of tweets were sensitizing.
      Independent factors associated with posting sensitizing tweets were women who
      experienced an abnormal smear test (OR [odds ratio] 13.456, 95% CI 3.101-58.378,
      P<.001), female gender (OR 3.752, 95% CI 2.133-6.598, P<.001), and people who
      live in the United Kingdom (OR 2.097, 95% CI 1.447-3.038, P<.001). Nonsensitizing
      tweets were statistically more posted by a nonhealth or nonmedia company (OR
      0.558, 95% CI 0.383-0.814, P<.001). CONCLUSIONS: This study demonstrates that the
      success of a public health campaign using a social media platform depends on its
      ability to get its targets involved. It also suggests the need to use social
      marketing to help its dissemination. The clinical impact of this Twitter campaign
      to increase cervical cancer screening is yet to be evaluated.

PMID- 29038097
TI  - Recommending Education Materials for Diabetic Questions Using Information
      Retrieval Approaches.
AB  - BACKGROUND: Self-management is crucial to diabetes care and providing expert
      vetted content for answering patients' questions is crucial in facilitating
      patient self-management. OBJECTIVE: The aim is to investigate the use of
      information retrieval techniques in recommending patient education materials for
      diabetic questions of patients. METHODS: We compared two retrieval algorithms,
      one based on Latent Dirichlet Allocation topic modeling (topic modeling-based
      model) and one based on semantic group (semantic group-based model), with the
      baseline retrieval models, vector space model (VSM), in recommending diabetic
      patient education materials to diabetic questions posted on the TuDiabetes forum.
      The evaluation was based on a gold standard dataset consisting of 50 randomly
      selected diabetic questions where the relevancy of diabetic education materials
      to the questions was manually assigned by two experts. The performance was
      assessed using precision of top-ranked documents. RESULTS: We retrieved 7510
      diabetic questions on the forum and 144 diabetic patient educational materials
      from the patient education database at Mayo Clinic. The mapping rate of words in
      each corpus mapped to the Unified Medical Language System (UMLS) was
      significantly different (P<.001). The topic modeling-based model outperformed the
      other retrieval algorithms. For example, for the top-retrieved document, the
      precision of the topic modeling-based, semantic group-based, and VSM models was
      67.0%, 62.8%, and 54.3%, respectively. CONCLUSIONS: This study demonstrated that
      topic modeling can mitigate the vocabulary difference and it achieved the best
      performance in recommending education materials for answering patients'
      questions. One direction for future work is to assess the generalizability of our
      findings and to extend our study to other disease areas, other patient education
      material resources, and online forums.

PMID- 29038098
TI  - Tackling Regional Public Health Issues Using Mobile Health Technology: Event
      Report of an mHealth Hackathon in Thailand.
AB  - Hackathons are intense, short, collaborative events focusing on solving real
      world problems through interdisciplinary teams. This is a report of the mHealth
      hackathon hosted by Khon Kaen University in collaboration with MIT Sana and
      faculty members from Harvard Medical School with the aim to improve health care
      delivery in the Northeast region of Thailand. Key health challenges, such as
      improving population health literacy, tracking disease trajectory and outcomes
      among rural communities, and supporting the workflow of overburdened frontline
      providers, were addressed using mHealth. Many modifications from the usual format
      of hackathon were made to tailor the event to the local context and culture, such
      as the process of recruiting participants and how teams were matched and formed.
      These modifications serve as good learning points for hosting future hackathons.
      There are also many lessons learned about how to achieve a fruitful collaboration
      despite cultural barriers, how to best provide mentorship to the participants,
      how to instill in the participants a sense of mission, and how to match the
      participants in a fair and efficient manner. This event showcases how
      interdisciplinary collaboration can produce results that are unattainable by any
      discipline alone and demonstrates that innovations are the fruits of collective
      wisdom of people from different fields of expertise who work together toward the
      same goals.

PMID- 29038100
TI  - GP who had "wholly inappropriate" relations with patient is struck off.

PMID- 29038101
TI  - Influence of Intramyocardial Adipose Tissue on the Accuracy of Endocardial
      Contact Mapping of the Chronic Myocardial Infarction Substrate.
AB  - BACKGROUND: Recent studies have demonstrated that intramyocardial adipose tissue
      (IMAT) may contribute to ventricular electrophysiological remodeling in patients
      with chronic myocardial infarction. Using an ovine model of myocardial
      infarction, we aimed to determine the influence of IMAT on scar tissue
      identification during endocardial contact mapping and optimal voltage-based
      mapping criteria for defining IMAT dense regions. METHOD AND RESULTS: In 7 sheep,
      left ventricular endocardial and transmural mapping was performed 84 weeks (15
      111 weeks) post-myocardial infarction. Spearman rank correlation coefficient was
      used to assess the relationship between endocardial contact electrogram amplitude
      and histological composition of myocardium. Receiver operator characteristic
      curves were used to derive optimal electrogram thresholds for IMAT delineation
      during endocardial mapping and to describe the use of endocardial mapping for
      delineation of IMAT dense regions within scar. Endocardial electrogram amplitude
      correlated significantly with IMAT (unipolar r=-0.48+/-0.12, P<0.001; bipolar r=
      0.45+/-0.22, P=0.04) but not collagen (unipolar r=-0.36+/-0.24, P=0.13; bipolar
      r=-0.43+/-0.31, P=0.16). IMAT dense regions of myocardium reliably identified
      using endocardial mapping with thresholds of <3.7 and <0.6 mV, respectively, for
      unipolar, bipolar, and combined modalities (single modality area under the
      curve=0.80, P<0.001; combined modality area under the curve=0.84, P<0.001).
      Unipolar mapping using optimal thresholding remained significantly reliable (area
      under the curve=0.76, P<0.001) during mapping of IMAT, confined to putative scar
      border zones (bipolar amplitude, 0.5-1.5 mV). CONCLUSIONS: These novel findings
      enhance our understanding of the confounding influence of IMAT on endocardial
      scar mapping. Combined bipolar and unipolar voltage mapping using optimal
      thresholds may be useful for delineating IMAT dense regions of myocardium, in
      postinfarct cardiomyopathy.

PMID- 29038099
TI  - Home Blood Pressure Management Intervention in Low- to Middle-Income Countries:
      Protocol for a Mixed Methods Study.
AB  - BACKGROUND: Control of hypertension in low- and middle-income countries (LMICs)
      is poor, often less than 10%. A strong body of evidence demonstrates that home
      blood pressure management lowers blood pressure, and recent guidelines from the
      National Institute for Clinical Health and Excellence recommends home blood
      pressure monitoring. However, the preponderance of data on the benefits of home
      blood pressure management comes from studies in high-income countries. OBJECTIVE:
      The objective of the study is to examine whether an intervention of home blood
      pressure management is feasible in LMICs. Home blood pressure management is
      defined as self-monitoring of blood pressure and self-titration of
      antihypertensive medications. We will identify barriers and facilitators of home
      blood pressure management and explore unique contextual factors in LMICs that
      influence implementation of home blood pressure management. METHODS: Participants
      will be recruited from 6 sites from 2015 to 2018. Patients and health care
      workers will be included. We will use mixed methods including focus groups,
      interviews, and standardized checklists. When possible, we will adapt materials
      from prior successful studies so that they are culturally and contextually
      appropriate. RESULTS: This ongoing study is funded by the World Heart Federation.
      The information that is obtained will be used to develop a randomized clinical
      trial of home blood pressure management in LMICs. CONCLUSIONS: The data generated
      from this qualitative study will provide much needed information from patients
      and health care workers about barriers and facilitators of home blood pressure
      management and unique contextual factors that might influence implementation of
      home blood pressure management in LMICs.

PMID- 29038102
TI  - ST-Elevation Magnitude Correlates With Right Ventricular Outflow Tract Conduction
      Delay in Type I Brugada ECG.
AB  - BACKGROUND: The substrate location and underlying electrophysiological mechanisms
      that contribute to the characteristic ECG pattern of Brugada syndrome (BrS) are
      still debated. Using noninvasive electrocardiographical imaging, we studied whole
      heart conduction and repolarization patterns during ajmaline challenge in BrS
      individuals. METHODS AND RESULTS: A total of 13 participants (mean age, 44+/-12
      years; 8 men), 11 concealed patients with type I BrS and 2 healthy controls,
      underwent an ajmaline infusion with electrocardiographical imaging and ECG
      recordings. Electrocardiographical imaging activation recovery intervals and
      activation timings across the right ventricle (RV) body, outflow tract (RVOT),
      and left ventricle were calculated and analyzed at baseline and when type I BrS
      pattern manifested after ajmaline infusion. Peak J-ST point elevation was
      calculated from the surface ECG and compared with the electrocardiographical
      imaging-derived parameters at the same time point. After ajmaline infusion, the
      RVOT had the greatest increase in conduction delay (5.4+/-2.8 versus 2.0+/-2.8
      versus 1.1+/-1.6 ms; P=0.007) and activation recovery intervals prolongation
      (69+/-32 versus 39+/-29 versus 21+/-12 ms; P=0.0005) compared with RV or left
      ventricle. In controls, there was minimal change in J-ST point elevation,
      conduction delay, or activation recovery intervals at all sites with ajmaline. In
      patients with BrS, conduction delay in RVOT, but not RV or left ventricle,
      correlated to the degree of J-ST point elevation (Pearson R, 0.81; P<0.001). No
      correlation was found between J-ST point elevation and activation recovery
      intervals prolongation in the RVOT, RV, or left ventricle. CONCLUSIONS: Magnitude
      of ST (J point) elevation in the type I BrS pattern is attributed to degree of
      conduction delay in the RVOT and not prolongation in repolarization time.

PMID- 29038103
TI  - Large Genomic Rearrangements of Desmosomal Genes in Italian Arrhythmogenic
      Cardiomyopathy Patients.
AB  - BACKGROUND: Arrhythmogenic cardiomyopathy (AC) is an inherited heart muscle
      disease associated with point mutations in genes encoding for cardiac desmosome
      proteins. Conventional mutation screening is positive in ~50% of probands. Copy
      number variations (CNVs) have recently been linked to AC pointing to the need to
      determine the prevalence of CNVs in desmosomal genes and to evaluate disease
      penetrance by cosegregation analysis in family members. METHODS AND RESULTS: A
      total of 160 AC genotype-negative probands for 5 AC desmosomal genes by
      conventional mutation screening underwent multiplex ligation-dependent probe
      amplification. Nine heterozygous CNVs were identified in 11 (6.9%) of the 160
      probands. Five carried a deletion of the entire plakophilin-2 (PKP2) gene, 2 a
      deletion of only PKP2 exon 4, 1 a deletion of the PKP2 exons 6 to 11, 1 a PKP2
      duplication of 5' untranslated region till exon 1, 1 the desmocollin-2 (DSC2)
      duplication of exons 7 to 9, and 1 a large deletion of chromosome 18 comprising
      both DSC2 and desmoglein-2 genes. All probands were affected by moderate-severe
      forms of the disease, whereas 10 (32%) of the 31 family members carrying one of
      these deletions fulfilled the diagnostic criteria. CONCLUSIONS: Genomic
      rearrangements were detected in ~7% of AC probands negative for pathogenic point
      mutations in desmosomal genes, highlighting the potential of CNVs analysis to
      substantially increase the diagnostic yield of genetic testing. Genotype
      phenotype correlation demonstrated the presence of the disease in about one third
      of family members carrying the CNV, underlying the role of other factors in the
      development and progression of the disease.

PMID- 29038105
TI  - Letter by Di Marco et al Regarding Article, "Electrical and Structural Substrate
      of Arrhythmogenic Right Ventricular Cardiomyopathy Determined Using Noninvasive
      Electrocardiographic Imaging and Late Gadolinium Magnetic Resonance Imaging".

PMID- 29038104
TI  - Safety of Oral Dofetilide Reloading for Treatment of Atrial Arrhythmias.
AB  - BACKGROUND: Although dofetilide labeling states that the drug must be initiated
      or reinitiated with continuous electrocardiographic monitoring and in the
      presence of trained personnel, the risks of dofetilide reloading justifying
      repeat hospitalization have not been investigated. METHODS AND RESULTS: Patients
      admitted for dofetilide reloading for atrial arrhythmias were retrospectively
      reviewed. The need for dose adjustment and the incidence of torsades de pointes
      (TdP) were identified. The incidence of TdP in dofetilide reloading was compared
      with patients admitted for dofetilide initial loading. Of 138 patients admitted
      for dofetilide reloading for atrial arrhythmias, 102 were reloaded at a
      previously tolerated dose, 30 with a higher dose from a previously tolerated dose
      and 2 at a lower dose; prior dosage was unknown in 4 patients. Dose adjustment or
      discontinuation was required in 44 patients (31.9%). No TdP occurred in the same
      dose reloading group, but TdP occurred in 2 patients admitted to increase
      dofetilide dosage (0% versus 6.7%; P=0.050). Dofetilide dose adjustment or
      discontinuation was required in 30 of 102 patients (29.4%) reloaded at a
      previously tolerated dose and in 11 of 30 patients (36.7%) admitted for an
      increase in dose. CONCLUSIONS: Although no TdP occurred in patients admitted to
      reload dofetilide at the same dose as previously tolerated, dosage adjustments or
      discontinuation was frequent and support the need for hospitalization for
      dofetilide reloading. Patients admitted for reloading with a higher dose tended
      to be at higher risk for TdP than patients reloaded at a prior tolerated dose.

PMID- 29038106
TI  - Response by Andrews et al to Letter Regarding Article, "Electrical and Structural
      Substrate of Arrhythmogenic Right Ventricular Cardiomyopathy Determined Using
      Noninvasive Electrocardiographic Imaging and Late Gadolinium Magnetic Resonance
      Imaging".

PMID- 29038107
TI  - Law of Spatial Averaging During Endocardial Voltage Mapping: You Can't Trim Out
      the Fat!

PMID- 29038108
TI  - Ajmaline-Induced Slowing of Conduction in the Right Ventricular Outflow Tract
      Cannot Account for ST Elevation in Patients With Type I Brugada ECG.

PMID- 29038109
TI  - Unraveling Missing Genes and Missing Inheritance in Arrhythmogenic
      Cardiomyopathy.

PMID- 29038111
TI  - What Is New on the Website.

PMID- 29038110
TI  - Dofetilide Reloaded: To Admit or Not to Admit, That is the Question.

PMID- 29038112
TI  - Interplay between Microbes and the Circadian Clock.
AB  - Circadian rhythms influence virtually all life forms on our planet, a notion that
      opens the question on how the circadian cycles of individual organisms may
      interplay with each other. In mammals, a potentially dangerous environmental
      stress is represented by encounters with infectious agents. Microbial attack is a
      major risk for organismal homeostasis and therefore needs to be efficiently
      counteracted by mechanisms implemented by the host immune system. Accumulating
      evidence shows that the immune system may anticipate an emerging pathogenic
      exposure through an enhanced inflammatory state. Notably, the circadian clock
      orchestrates these anticipatory responses to fluctuating conditions in the
      external world. In this article, we review the current knowledge about the
      relationship between the circadian clock and pathogenic infections. We discuss
      the role of the circadian clock against infection and specific pathogens, the
      core clock proteins involved in the defense mechanisms, and the specific tissue
      or cell type in which they function to counteract the infection. Finally,
      circadian oscillations in the gut microbiome composition and its possible role in
      protecting against foodborne pathogen colonization are presented.

PMID- 29038114
TI  - Inflammasome-Dependent Cytokines at the Crossroads of Health and Autoinflammatory
      Disease.
AB  - As key regulators of both innate and adaptive immunity, it is unsurprising that
      the activity of interleukin (IL)-1 cytokine family members is tightly controlled
      by decoy receptors, antagonists, and a variety of other mechanisms. Additionally,
      inflammasome-mediated proteolytic maturation is a prominent and distinguishing
      feature of two important members of this cytokine family, IL-1beta and IL-18,
      because their full-length gene products are biologically inert. Although vital in
      antimicrobial host defense, deregulated inflammasome signaling is linked with a
      growing number of autoimmune and autoinflammatory diseases. Here, we focus on
      introducing the diverse inflammasome types and discussing their causal roles in
      periodic fever syndromes. Therapies targeting IL-1 or IL-18 show great efficacy
      in some of these autoinflammatory diseases, although further understanding of the
      molecular mechanisms leading to unregulated production of these key cytokines is
      required to benefit more patients.

PMID- 29038115
TI  - The Common Cytokine Receptor gamma Chain Family of Cytokines.
AB  - Interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21 form a family of cytokines
      based on their sharing the common cytokine receptor gamma chain (gammac), which
      was originally discovered as the third receptor component of the IL-2 receptor,
      IL-2Rgamma. The IL2RG gene is located on the X chromosome and is mutated in
      humans with X-linked severe combined immunodeficiency (XSCID). The breadth of the
      defects in XSCID could not be explained solely by defects in IL-2 signaling, and
      it is now clear that gammac is a shared receptor component of the six cytokines
      noted above, making XSCID a disease of defective cytokine signaling. Janus kinase
      (JAK)3 associates with gammac, and JAK3-deficient SCID phenocopies XSCID,
      findings that served to stimulate the development of JAK3 inhibitors as
      immunosuppressants. gammac family cytokines collectively control broad aspects of
      lymphocyte development, growth, differentiation, and survival, and these
      cytokines are clinically important, related to allergic and autoimmune diseases
      and cancer as well as immunodeficiency. In this review, we discuss the actions of
      these cytokines, their critical biological roles and signaling pathways, focusing
      mainly on JAK/STAT (signal transducers and activators of transcription)
      signaling, and how this information is now being used in clinical therapeutic
      efforts.

PMID- 29038113
TI  - Will Systems Biology Deliver Its Promise and Contribute to the Development of New
      or Improved Vaccines? From Data to Understanding through Systems Biology.
AB  - The advent of high-throughput "omics" technologies, combined with the
      computational and statistical methods necessary to analyze such data, have
      revolutionized biology, enabling a global view of the complex molecular processes
      and interactions that occur within a biological system. Such systems-based
      approaches have begun to be used in the evaluation of immune responses to
      vaccination, with the promise of identifying predictive biomarkers capable of
      rapidly evaluating vaccine efficacy, transforming our understanding of the immune
      mechanisms responsible for protective responses to vaccination and contributing
      to a new generation of rationally designed vaccines. Here we present our opinion
      that systems biology does indeed have a critical role in the future of
      vaccinology. Such approaches have shown potential in identifying transcriptional
      and cellular signatures of responsiveness to vaccination using diverse vaccines,
      adjuvants, and human populations. These findings, coupled with further
      mechanistic evaluation in animal models, will guide development of targeted
      vaccine and adjuvant formulations designed to optimally induce protective
      responses in populations of differing immune status.

PMID- 29038116
TI  - Design Principles of Phosphorylation-Dependent Timekeeping in Eukaryotic
      Circadian Clocks.
AB  - The circadian clock in cyanobacteria employs a posttranslational oscillator
      composed of a sequential phosphorylation-dephosphorylation cycle of KaiC protein,
      in which the dynamics of protein structural changes driven by temperature
      compensated KaiC's ATPase activity are critical for determining the period. On
      the other hand, circadian clocks in eukaryotes employ transcriptional feedback
      loops as a core mechanism. In this system, the dynamics of protein accumulation
      and degradation affect the circadian period. However, recent studies of
      eukaryotic circadian clocks reveal that the mechanism controlling the circadian
      period can be independent of the regulation of protein abundance. Instead, the
      circadian substrate is often phosphorylated at multiple sites at flexible protein
      regions to induce structural changes. The phosphorylation is catalyzed by kinases
      that induce sequential multisite phosphorylation such as casein kinase 1 (CK1)
      with temperature-compensated activity. We propose that the design principles of
      phosphorylation-dependent circadian-period determination in eukaryotes may share
      characteristics with the posttranslational oscillator in cyanobacteria.

PMID- 29038117
TI  - Will Systems Biology Deliver Its Promise and Contribute to the Development of New
      or Improved Vaccines? Systems Biology Views of Vaccine Innate and Adaptive
      Immunity.
AB  - During the last decade, several high-throughput technologies have been applied to
      gather deeper understanding on the biological events elicited by vaccination. The
      main goal of systems biology is to integrate different sources of data and
      extract biologically meaningful information. This holistic approach has provided
      new insights on the impact that the innate immune status has on vaccine
      responsiveness. Other factors like chronic infections, age, microbiome, and
      metabolism can influence the outcome of vaccination, and systems biology offers
      unique opportunities to expand our understanding of their role on the immune
      response. However, a few challenges that still need to be overcome will be
      discussed.

PMID- 29038118
TI  - Introduction to Chronobiology.
AB  - A diverse range of species, from cyanobacteria to humans, evolved endogenous
      biological clocks that allow for the anticipation of daily variations in light
      and temperature. The ability to anticipate regular environmental rhythms promotes
      optimal performance and survival. Herein we present a brief historical timeline
      of how circadian concepts and terminology have emerged since the early
      observation of daily leaf movement in plants made by an astronomer in the 1700s.

PMID- 29038120
TI  - Will Systems Biology Deliver Its Promise and Contribute to the Development of New
      or Improved Vaccines? What Really Constitutes the Study of "Systems Biology" and
      How Might Such an Approach Facilitate Vaccine Design.
AB  - A dichotomy exists in the field of vaccinology about the promise versus the hype
      associated with application of "systems biology" approaches to rational vaccine
      design. Some feel it is the only way to efficiently uncover currently unknown
      parameters controlling desired immune responses or discover what elements
      actually mediate these responses. Others feel that traditional experimental,
      often reductionist, methods for incrementally unraveling complex biology provide
      a more solid way forward, and that "systems" approaches are costly ways to
      collect data without gaining true insight. Here I argue that both views are
      inaccurate. This is largely because of confusion about what can be gained from
      classical experimentation versus statistical analysis of large data sets
      (bioinformatics) versus methods that quantitatively explain emergent properties
      of complex assemblies of biological components, with the latter reflecting what
      was previously called "physiology." Reductionist studies will remain essential
      for generating detailed insight into the functional attributes of specific
      elements of biological systems, but such analyses lack the power to provide a
      quantitative and predictive understanding of global system behavior. But by
      employing (1) large-scale screening methods for discovery of unknown components
      and connections in the immune system (omics), (2) statistical analysis of large
      data sets (bioinformatics), and (3) the capacity of quantitative computational
      methods to translate these individual components and connections into models of
      emergent behavior (systems biology), we will be able to better understand how the
      overall immune system functions and to determine with greater precision how to
      manipulate it to produce desired protective responses.

PMID- 29038119
TI  - Will Systems Biology Deliver Its Promise and Contribute to the Development of New
      or Improved Vaccines? Seeing the Forest Rather than a Few Trees.
AB  - Preventing morbidity and mortality from infectious disease through the
      development and use of effective vaccines is one of medicine's greatest
      achievements and greatest frustrations. We are struggling with improving vaccine
      efficacy for some of the most globally widespread diseases, such as malaria and
      tuberculosis. In an effort to gain an edge, systems biology approaches have begun
      to be employed to more broadly investigate the pathways leading to protective
      vaccine responses. As such, we are now at a critical juncture, needing to
      evaluate how fruitful these approaches have been. Herein we discuss the level of
      success achieved as compared to the original promise of systems methodologies,
      and conclude that while we have indeed begun to make clear inroads into
      understanding the immune response to vaccines, we still have much to learn and
      gain from the more comprehensive approach of systems-level analysis.

PMID- 29038121
TI  - Targeting IL-10 Family Cytokines for the Treatment of Human Diseases.
AB  - Members of the interleukin (IL)-10 family of cytokines play important roles in
      regulating immune responses during host defense but also in autoimmune disorders,
      inflammatory diseases, and cancer. Although IL-10 itself primarily acts on
      leukocytes and has potent immunosuppressive functions, other family members
      preferentially target nonimmune compartments, such as tissue epithelial cells,
      where they elicit innate defense mechanisms to control viral, bacterial, and
      fungal infections, protect tissue integrity, and promote tissue repair and
      regeneration. As cytokines are prime drug targets, IL-10 family cytokines provide
      great opportunities for the treatment of autoimmune diseases, tissue damage, and
      cancer. Yet no therapy in this space has been approved to date. Here, we
      summarize the diverse biology of the IL-10 family as it relates to human disease
      and review past and current strategies and challenges to target IL-10 family
      cytokines for clinical use.

PMID- 29038122
TI  - Whales, lifespan, phospholipids, and cataracts.
AB  - This study addresses the question: why do rats get cataracts at 2 years, dogs at
      8 years, and whales do not develop cataracts for 200 years? Whale lens lipid
      phase transitions were compared with the phase transitions of other species that
      were recalculated. The major phospholipids of the whale lens were sphingolipids,
      mostly dihydrosphingomyelins with an average molar cholesterol/phospholipid ratio
      of 10. There was a linear correlation between the percentage of lens sphingolipid
      and lens lipid hydrocarbon chain order until about 60% sphingolipid. The
      percentage of lens sphingolipid correlated with the lens lipid phase transition
      temperature. The lifespan of the bowhead whale was the longest of the species
      measured and the percentage of whale lens sphingolipid fit well in the
      correlation between the percentage of lens sphingolipid and lifespan for many
      species. In conclusion, bowhead whale lens membranes have a high sphingolipid
      content that confers resistance to oxidation, allowing these lenses to stay clear
      relatively longer than many other species. The strong correlation between
      sphingolipid and lifespan may form a basis for future studies, which are needed
      because correlations do not infer cause. One could hope that if human lenses
      could be made to have a lipid composition similar to whales, like the bowhead,
      humans would not develop age-related cataracts for over 100 years.

PMID- 29038123
TI  - Lactobacillus rhamnosus L34 Attenuates Gut Translocation-Induced Bacterial Sepsis
      in Murine Models of Leaky Gut.
AB  - Gastrointestinal (GI) bacterial translocation in sepsis is well known, but the
      role of Lactobacillus species probiotics is still controversial. We evaluated the
      therapeutic effects of Lactobacillus rhamnosus L34 in a new sepsis model of oral
      administration of pathogenic bacteria with GI leakage induced by either an
      antibiotic cocktail (ATB) and/or dextran sulfate sodium (DSS). GI leakage with
      ATB, DSS, and DSS plus ATB (DSS+ATB) was demonstrated by fluorescein
      isothiocyanate (FITC)-dextran translocation to the circulation. The
      administration of pathogenic bacteria, either Klebsiella pneumoniae or Salmonella
      enterica serovar Typhimurium, enhanced translocation. Bacteremia was demonstrated
      within 24 h in 50 to 88% of mice with GI leakage plus the administration of
      pathogenic bacteria but not with GI leakage induction alone or bacterial gavage
      alone. Salmonella bacteremia was found in only 16 to 29% and 0% of mice with
      Salmonella and Klebsiella administrations, respectively. Klebsiella bacteremia
      was demonstrated in 25 to 33% and 10 to 16% of mice with Klebsiella and
      Salmonella administrations, respectively. Lactobacillus rhamnosus L34 attenuated
      GI leakage in these models, as shown by the reductions of FITC-dextran gut
      translocation, serum interleukin-6 (IL-6) levels, bacteremia, and sepsis
      mortality. The reduction in the amount of fecal Salmonella bacteria with
      Lactobacillus treatment was demonstrated. In addition, an anti-inflammatory
      effect of the conditioned medium from Lactobacillus rhamnosus L34 was also
      demonstrated by the attenuation of cytokine production in colonic epithelial
      cells in vitro In conclusion, Lactobacillus rhamnosus L34 attenuated the severity
      of symptoms in a murine sepsis model induced by GI leakage and the administration
      of pathogenic bacteria.

PMID- 29038124
TI  - Plasmodium falciparum PfEMP1 Modulates Monocyte/Macrophage Transcription Factor
      Activation and Cytokine and Chemokine Responses.
AB  - Immunity to Plasmodium falciparum malaria is slow to develop, and it is often
      asserted that malaria suppresses host immunity, although this is poorly
      understood and the molecular basis for such activity remains unknown. P.
      falciparum erythrocyte membrane protein 1 (PfEMP1) is a virulence factor that
      plays a key role in parasite-host interactions. We investigated the
      immunosuppressive effect of PfEMP1 on monocytes/macrophages, which are central to
      the antiparasitic innate response. RAW macrophages and human primary monocytes
      were stimulated with wild-type 3D7 or CS2 parasites or transgenic PfEMP1-null
      parasites. To study the immunomodulatory effect of PfEMP1, transcription factor
      activation and cytokine and chemokine responses were measured. The level of
      activation of NF-kappaB was significantly lower in macrophages stimulated with
      parasites that express PfEMP1 at the red blood cell surface membrane than in
      macrophages stimulated with PfEMP1-null parasites. Modulation of additional
      transcription factors, including CREB, also occurred, resulting in reduced immune
      gene expression and decreased tumor necrosis factor (TNF) and interleukin-10 (IL
      10) release. Similarly, human monocytes released less IL-1beta, IL-6, IL-10,
      monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein
      1alpha (MIP-1alpha), MIP-1beta, and TNF specifically in response to VAR2CSA
      PfEMP1-containing parasites than in response to PfEMP1-null parasites, suggesting
      that this immune regulation by PfEMP1 is important in naturally occurring
      infections. These results indicate that PfEMP1 is an immunomodulatory molecule
      that affects the activation of a range of transcription factors, dampening
      cytokine and chemokine responses. Therefore, these findings describe a potential
      molecular basis for immune suppression by P. falciparum.

PMID- 29038125
TI  - Modulators of Enterococcus faecalis Cell Envelope Integrity and Antimicrobial
      Resistance Influence Stable Colonization of the Mammalian Gastrointestinal Tract.
AB  - The Gram-positive bacterium Enterococcus faecalis is both a colonizer of the
      gastrointestinal tract (GIT) and an agent of serious nosocomial infections.
      Although it is typically required for pathogenesis, GIT colonization by E.
      faecalis is poorly understood. E. faecalis tolerates high concentrations of GIT
      antimicrobials, like cholate and lysozyme, leading us to hypothesize that
      resistance to intestinal antimicrobials is essential for long-term GIT
      colonization. Analyses of E. faecalis mutants exhibiting defects in antimicrobial
      resistance revealed that IreK, a determinant of envelope integrity and
      antimicrobial resistance, is required for long-term GIT colonization. IreK is a
      member of the PASTA kinase protein family, bacterial transmembrane signaling
      proteins implicated in the regulation of cell wall homeostasis. Among several
      determinants of cholate and lysozyme resistance in E. faecalis, IreK was the only
      one found to be required for intestinal colonization, emphasizing the importance
      of this protein to enterococcal adaptation to the GIT. By studying DeltaireK
      suppressor mutants that recovered the ability to colonize the GIT, we identified
      two conserved enterococcal proteins (OG1RF_11271 and OG1RF_11272) that function
      antagonistically to IreK and interfere with cell envelope integrity,
      antimicrobial resistance, and GIT colonization. Our data suggest that IreK,
      through its kinase activity, inhibits the actions of these proteins. IreK,
      OG1RF_11271, and OG1RF_11272 are found in all enterococci, suggesting that their
      effect on GIT colonization is universal across enterococci. Thus, we have defined
      conserved genes in the enterococcal core genome that influence GIT colonization
      through their effect on enterococcal envelope integrity and antimicrobial
      resistance.

PMID- 29038126
TI  - Transcervical Inoculation with Chlamydia trachomatis Induces Infertility in HLA
      DR4 Transgenic and Wild-Type Mice.
AB  - Chlamydia trachomatis is the leading cause of infection-induced infertility in
      women. Attempts to control this epidemic with screening programs and antibiotic
      therapy have failed. Currently, a vaccine to prevent C. trachomatis infections is
      not available. In order to develop an animal model for evaluating vaccine
      antigens that can be applied to humans, we used C. trachomatis serovar D (strain
      UW-3/Cx) to induce infertility in mice whose major histocompatibility complex
      class II antigen was replaced with the human leukocyte antigen DR4 (HLA-DR4).
      Transcervical inoculation of medroxyprogesterone-treated HLA-DR4 transgenic mice
      with 5 * 105C. trachomatis D inclusion forming units (IFU) induced a significant
      reduction in fertility, with a mean number of embryos/mouse of 4.4 +/- 1.3
      compared to 7.8 +/- 0.5 for the uninfected control mice (P < 0.05). A similar
      fertility reduction was elicited in the wild-type (WT) C57BL/6 mice (4.3 +/- 1.4
      embryos/mouse) compared to the levels of the WT controls (9.1 +/- 0.4
      embryos/mouse) (P < 0.05). Following infection, WT mice mounted more robust
      humoral and cellular immune responses than HLA-DR4 mice. As determined by vaginal
      shedding, HLA-DR4 mice were more susceptible to a transcervical C. trachomatis D
      infection than WT mice. To assess if HLA-DR4 transgenic and WT mice could be
      protected by vaccination, 104 IFU of C. trachomatis D was delivered intranasally,
      and mice were challenged transcervically 6 weeks later with 5 * 105 IFU of C.
      trachomatis D. As determined by severity and length of vaginal shedding, WT
      C57BL/6 and HLA-DR4 mice were significantly protected by vaccination. The
      advantages and limitations of the HLA-DR4 transgenic mouse model for evaluating
      human C. trachomatis vaccine antigens are discussed.

PMID- 29038127
TI  - The Genital Tract Virulence Factor pGP3 Is Essential for Chlamydia muridarum
      Colonization in the Gastrointestinal Tract.
AB  - The cryptic plasmid is essential for Chlamydia muridarum dissemination from the
      genital tract to the gastrointestinal (GI) tract. Following intravaginal
      inoculation, a C. muridarum strain deficient in plasmid-encoded pGP3 or pGP4 but
      not pGP5, pGP7, or pGP8 failed to spread to the mouse gastrointestinal tract,
      although mice infected with these strains developed productive genital tract
      infections. pGP3- or pGP4-deficient strains also failed to colonize the
      gastrointestinal tract when delivered intragastrically. pGP4 regulates pGP3,
      while pGP3 does not affect pGP4 expression, indicating that pGP3 is critical for
      C. muridarum colonization of the gastrointestinal tract. Mutants deficient in
      GlgA, a chromosome-encoded protein regulated by pGP4, also consistently colonized
      the mouse gastrointestinal tract. Interestingly, C. muridarum colonization of the
      gastrointestinal tract positively correlated with pathogenicity in the upper
      genital tract. pGP3-deficient C. muridarum strains did not induce hydrosalpinx or
      spread to the GI tract even when delivered to the oviduct by intrabursal
      inoculation. Thus, the current study not only has revealed that pGP3 is a novel
      chlamydial colonization factor in the gastrointestinal tract but also has laid a
      foundation for investigating the significance of gastrointestinal Chlamydia.

PMID- 29038128
TI  - Microbial Composition Predicts Genital Tract Inflammation and Persistent
      Bacterial Vaginosis in South African Adolescent Females.
AB  - Young African females are at an increased risk of HIV acquisition, and genital
      inflammation or the vaginal microbiome may contribute to this risk. We studied
      these factors in 168 HIV-negative South African adolescent females aged 16 to 22
      years. Unsupervised clustering of 16S rRNA gene sequences revealed three clusters
      (subtypes), one of which was strongly associated with genital inflammation. In a
      multivariate model, the microbiome compositional subtype and hormonal
      contraception were significantly associated with genital inflammation. We
      identified 40 taxa significantly associated with inflammation, including those
      reported previously (Prevotella, Sneathia, Aerococcus, Fusobacterium, and
      Gemella) as well as several novel taxa (including increased frequencies of
      bacterial vaginosis-associated bacterium 1 [BVAB1], BVAB2, BVAB3, Prevotella
      amnii, Prevotella pallens, Parvimonas micra, Megasphaera, Gardnerella vaginalis,
      and Atopobium vaginae and decreased frequencies of Lactobacillus reuteri,
      Lactobacillus crispatus, Lactobacillus jensenii, and Lactobacillus iners). Women
      with inflammation-associated microbiomes had significantly higher body mass
      indices and lower levels of endogenous estradiol and luteinizing hormone.
      Community functional profiling revealed three distinct vaginal microbiome
      subtypes, one of which was characterized by extreme genital inflammation and
      persistent bacterial vaginosis (BV); this subtype could be predicted with high
      specificity and sensitivity based on the Nugent score (>=9) or BVAB1 abundance.
      We propose that women with this BVAB1-dominated subtype may have chronic genital
      inflammation due to persistent BV, which may place them at a particularly high
      risk for HIV infection.

PMID- 29038129
TI  - Native or Proteolytically Activated NanI Sialidase Enhances the Binding and
      Cytotoxic Activity of Clostridium perfringens Enterotoxin and Beta Toxin.
AB  - Many Clostridium perfringens strains produce NanI as their major sialidase.
      Previous studies showed that NanI could potentiate C. perfringens epsilon toxin
      cytotoxicity by enhancing the binding of this toxin to host cells. The present
      study first determined that NanI exerts similar cytotoxicity-enhancing effects on
      C. perfringens enterotoxin and beta toxin, which are also important toxins for C.
      perfringens diseases (enteritis and enterotoxemia) originating in the
      gastrointestinal (GI) tract. Building upon previous work demonstrating that
      purified trypsin can activate NanI activity, this study next determined that
      purified chymotrypsin or mouse intestinal fluids can also activate NanI activity.
      Amino acid sequencing then showed that this effect involves the N-terminal
      processing of the NanI protein. Recombinant NanI (rNanI) species corresponding to
      major chymotrypsin- or small intestinal fluid-generated NanI fragments possessed
      more sialidase activity than did full-length rNanI, further supporting the
      proteolytic activation of NanI activity. rNanI species corresponding to
      proteolysis products also promoted the cytotoxic activity and binding of
      enterotoxin and beta toxin more strongly than did full-length rNanI. Since
      enterotoxin and beta toxin are produced in the intestines during human and animal
      disease, these findings suggest that intestinal proteases may enhance NanI
      activity, which in turn could further potentiate the activity of intestinally
      active toxins during disease. Coupling these new results with previous findings
      demonstrating that NanI is important for the adherence of C. perfringens to
      enterocyte-like cells, NanI sialidase is now emerging as a potential auxiliary
      virulence factor for C. perfringens enteritis and enterotoxemia.

PMID- 29038130
TI  - Handling time varying confounding in observational research.

PMID- 29038131
TI  - Risk of infective endocarditis after dental procedures is extremely low.

PMID- 29038132
TI  - Provider Perspectives of High-Quality Pediatric Hospital-to-Home Transitions for
      Children and Youth With Chronic Disease.
AB  - OBJECTIVE: The objective of this study was to describe health care providers' and
      hospital administrators' perspectives on how to improve pediatric hospital-to
      home transitions for children and youth with chronic disease (CYCD). METHODS:
      Focus groups and key informant interviews of inpatient attending physicians,
      primary care physicians, pediatric residents, nurses, care coordinators, and
      social workers were conducted at a tertiary care children's hospital. Key
      informant interviews were performed with hospital administrators. Semistructured
      questions were used to elicit perceptions of transitional care quality and to
      identify key structures and processes needed to improve transitional care
      outcomes. Transcripts of discussions were coded to identify emergent themes.
      RESULTS: Participants (N = 22) reported that key structures needed to enhance
      transitional care were a multidisciplinary team, inpatient provider-patient
      continuity, hospital resource availability, an interoperative electronic health
      record, and availability of community resources. Key processes needed to achieve
      high-quality transitional care included setting individualized transition goals,
      involving parents in care planning, establishing parental competency with home
      care tasks, and consistently communicating with primary care physicians.
      Providers identified a lack of reliable roles and processes, insufficient
      assessment of patient and/or family psychosocial factors, and consistent 2-way
      communication with community providers as elements to target to improve
      transitional care outcomes for CYCD. CONCLUSIONS: Many key structures and
      processes of care perceived as important to achieving high-quality transitional
      care outcomes for CYCD have the opportunity for improvement at the institution
      studied. Engaging key stakeholders in designing quality improvement interventions
      to address these deficits in the current care model may improve transitional care
      outcomes for this vulnerable population.

PMID- 29038133
TI  - Did Jules Dejerine describe AMAN at the end of the 19th century?
AB  - Guillain-Barre syndrome (GBS) is a heterogeneous group of acute immune-mediated
      neuropathies, including acute inflammatory demyelinating polyneuropathy (AIDP)
      and acute motor axonal neuropathy (AMAN). AMAN is an axonal subtype of GBS that
      has been known since the 1990s; this term was first used to describe a summer
      epidemic of acute ascending paralysis observed in children in northern China (and
      Mexico). It is pathologically characterized by noninflammatory axonal
      degeneration of the motor nerves (with little or no demyelination). The French
      neurologist Jules Dejerine (1849-1917) conducted a clinical and pathologic
      description of AMAN in the late 19th century. We describe his observations, which
      provide us with valuable information on the course of pathologic lesions in this
      disease.

PMID- 29038135
TI  - Editors' Note.

PMID- 29038134
TI  - Fatigable ptosis as an initial presentation of adult-onset Leigh syndrome.

PMID- 29038136
TI  - Letter re: Ischemic Lesions, blood pressure dysregulation, and poor outcomes in
      intracerebral hemorrhage.

PMID- 29038137
TI  - Author response: Ischemic Lesions, blood pressure dysregulation, and poor
      outcomes in intracerebral hemorrhage.

PMID- 29038138
TI  - Letter re: Efficacy and safety of brivaracetam for partial-onset seizures in 3
      pooled clinical studies.

PMID- 29038139
TI  - Clinical Reasoning: A 46-year-old man with persistent hiccups, cognitive
      dysfunction, and imbalance.

PMID- 29038140
TI  - Teaching NeuroImages: Artery of Percheron thrombosis causing selective downgaze
      palsy.

PMID- 29038141
TI  - Teaching NeuroImages: Spontaneous involution of symptomatic delayed tumefactive
      cyst following radiosurgery for AVM.

PMID- 29038143
TI  - Teaching Video NeuroImages: My weeping patient: Avoiding the pitfalls of a
      functional diagnosis.

PMID- 29038142
TI  - Teaching NeuroImages: MR neurography for the diagnosis of hypertrophic
      neuropathies.

PMID- 29038144
TI  - Genetic Gain Increases by Applying the Usefulness Criterion with Improved
      Variance Prediction in Selection of Crosses.
AB  - A crucial step in plant breeding is the selection and combination of parents to
      form new crosses. Genome-based prediction guides the selection of high-performing
      parental lines in many crop breeding programs which ensures a high mean
      performance of progeny. To warrant maximum selection progress, a new cross should
      also provide a large progeny variance. The usefulness concept as measure of the
      gain that can be obtained from a specific cross accounts for variation in progeny
      variance. Here, it is shown that genetic gain can be considerably increased when
      crosses are selected based on their genomic usefulness criterion compared to
      selection based on mean genomic estimated breeding values. An efficient and
      improved method to predict the genetic variance of a cross based on Markov chain
      Monte Carlo samples of marker effects from a whole-genome regression model is
      suggested. In simulations representing selection procedures in crop breeding
      programs, the performance of this novel approach is compared with existing
      methods, like selection based on mean genomic estimated breeding values and
      optimal haploid values. In all cases, higher genetic gain was obtained compared
      with previously suggested methods. When 1% of progenies per cross were selected,
      the genetic gain based on the estimated usefulness criterion increased by 0.14
      genetic standard deviation compared to a selection based on mean genomic
      estimated breeding values. Analytical derivations of the progeny genotypic
      variance-covariance matrix based on parental genotypes and genetic map
      information make simulations of progeny dispensable, and allow fast
      implementation in large-scale breeding programs.

PMID- 29038145
TI  - Oncometabolites: A New Paradigm for Oncology, Metabolism, and the Clinical
      Laboratory.
AB  - BACKGROUND: Pediatric clinical laboratories commonly measure tricarboxylic acid
      cycle intermediates for screening, diagnosis, and monitoring of specific inborn
      errors of metabolism, such as organic acidurias. In the past decade, the same
      tricarboxylic acid cycle metabolites have been implicated and studied in cancer.
      The accumulation of these metabolites in certain cancers not only serves as a
      biomarker but also directly contributes to cellular transformation, therefore
      earning them the designation of oncometabolites. CONTENT: D-2-hydroxyglutarate, L
      2-hydroxyglutarate, succinate, and fumarate are the currently recognized
      oncometabolites. They are structurally similar and share metabolic proximity in
      the tricarboxylic acid cycle. As a result, they promote tumorigenesis in cancer
      cells through similar mechanisms. This review summarizes the currently understood
      common and distinct biological features of these compounds. In addition, we will
      review the current laboratory methodologies that can be used to quantify these
      metabolites and their downstream targets. SUMMARY: Oncometabolites play an
      important role in cancer biology. The metabolic pathways that lead to the
      production of oncometabolites and the downstream signaling pathways that are
      activated by oncometabolites represent potential therapeutic targets. Clinical
      laboratories have a critical role to play in the management of oncometabolite
      associated cancers through development and validation of sensitive and specific
      assays that measure oncometabolites and their downstream effectors. These assays
      can be used as screening tools and for follow-up to measure response to
      treatment, as well as to detect minimal residual disease and recurrence.

PMID- 29038148
TI  - The Potential and Pitfalls of a Dye-Assisted Paper-Based Assay for Blood
      Grouping.

PMID- 29038147
TI  - Imputation of Baseline LDL Cholesterol Concentration in Patients with Familial
      Hypercholesterolemia on Statins or Ezetimibe.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is the most frequent genetic
      disorder seen clinically and is characterized by increased LDL cholesterol (LDL
      C) (>95th percentile), family history of increased LDL-C, premature
      atherosclerotic cardiovascular disease (ASCVD) in the patient or in first-degree
      relatives, presence of tendinous xanthomas or premature corneal arcus, or
      presence of a pathogenic mutation in the LDLR, PCSK9, or APOB genes. A diagnosis
      of FH has important clinical implications with respect to lifelong risk of ASCVD
      and requirement for intensive pharmacological therapy. The concentration of
      baseline LDL-C (untreated) is essential for the diagnosis of FH but is often not
      available because the individual is already on statin therapy. METHODS: To
      validate a new algorithm to impute baseline LDL-C, we examined 1297 patients. The
      baseline LDL-C was compared with the imputed baseline obtained within 18 months
      of the initiation of therapy. We compared the percent reduction in LDL-C on
      treatment from baseline with the published percent reductions. RESULTS: After
      eliminating individuals with missing data, nonstandard doses of statins, or
      medications other than statins or ezetimibe, we provide data on 951 patients. The
      mean +/- SE baseline LDL-C was 243.0 (2.2) mg/dL [6.28 (0.06) mmol/L], and the
      mean +/- SE imputed baseline LDL-C was 244.2 (2.6) mg/dL [6.31 (0.07) mmol/L] (P
      = 0.48). There was no difference in response according to the patient's sex or in
      percent reduction between observed and expected for individual doses or types of
      statin or ezetimibe. CONCLUSIONS: We provide a validated estimation of baseline
      LDL-C for patients with FH that may help clinicians in making a diagnosis.

PMID- 29038146
TI  - Use of Metabolomics in Improving Assessment of Dietary Intake.
AB  - BACKGROUND: Nutritional metabolomics is rapidly evolving to integrate nutrition
      with complex metabolomics data to discover new biomarkers of nutritional exposure
      and status. CONTENT: The purpose of this review is to provide a broad overview of
      the measurement techniques, study designs, and statistical approaches used in
      nutrition metabolomics, as well as to describe the current knowledge from
      epidemiologic studies identifying metabolite profiles associated with the intake
      of individual nutrients, foods, and dietary patterns. SUMMARY: A wide range of
      technologies, databases, and computational tools are available to integrate
      nutritional metabolomics with dietary and phenotypic information. Biomarkers
      identified with the use of high-throughput metabolomics techniques include amino
      acids, acylcarnitines, carbohydrates, bile acids, purine and pyrimidine
      metabolites, and lipid classes. The most extensively studied food groups include
      fruits, vegetables, meat, fish, bread, whole grain cereals, nuts, wine, coffee,
      tea, cocoa, and chocolate. We identified 16 studies that evaluated metabolite
      signatures associated with dietary patterns. Dietary patterns examined included
      vegetarian and lactovegetarian diets, omnivorous diet, Western dietary patterns,
      prudent dietary patterns, Nordic diet, and Mediterranean diet. Although many
      metabolite biomarkers of individual foods and dietary patterns have been
      identified, those biomarkers may not be sensitive or specific to dietary intakes.
      Some biomarkers represent short-term intakes rather than long-term dietary
      habits. Nonetheless, nutritional metabolomics holds promise for the development
      of a robust and unbiased strategy for measuring diet. Still, this technology is
      intended to be complementary, rather than a replacement, to traditional well
      validated dietary assessment methods such as food frequency questionnaires that
      can measure usual diet, the most relevant exposure in nutritional epidemiologic
      studies.

PMID- 29038149
TI  - Partitioning the Genetic Architecture of Plasma Lipoprotein(a) and Kringle IV
      Type 2 Repeats: Implications for Therapeutic Lowering.

PMID- 29038150
TI  - Deep Learning Makes Its Way to the Clinical Laboratory.

PMID- 29038151
TI  - Obesity and Cancer: Evidence, Impact, and Future Directions.
AB  - BACKGROUND: Mounting evidence, particularly from prospective epidemiologic
      studies but with additional support from animal models and mechanistic studies,
      supported conclusions in 2016 by the International Agency for Research on Cancer
      (IARC) in their review of the preventive effects of weight control on cancer
      risk. CONTENT: The workgroup concluded that obesity is causally related to cancer
      at 13 anatomic sites (esophagus: adenocarcinoma; gastric cardia; colon and
      rectum; liver; gallbladder; pancreas; breast: postmenopausal; uterine
      endometrial; ovary; kidney: renal cell; meningioma; thyroid; and multiple
      myeloma). Further, avoiding weight gain and excess body fat will prevent cancer.
      Evidence on weight loss and reduction in risk of cancer is more limited. Ongoing
      clinical trials address the benefits of weight loss interventions after
      diagnosis. SUMMARY: Here, we review the evidence from the 2016 IARC that obesity
      is causally related to cancer at 13 anatomic sites and identify areas for future
      research, including the consequences of childhood adiposity, the relation between
      velocity of weight gain and cancer risk, and improved methods for analysis of
      life-course adiposity and cancer risk. Refining understanding of mechanisms may
      further inform prevention strategies.

PMID- 29038152
TI  - Harmonization of Viral Load Testing with the First International Standard for BK
      DNA.

PMID- 29038153
TI  - Prospective Validation of a Biomarker-Based Rule Out Strategy for Functionally
      Relevant Coronary Artery Disease.
AB  - BACKGROUND: This study aimed to prospectively advance a rule-out strategy for
      functionally significant coronary artery disease (CAD) by use of high-sensitivity
      cardiac troponin I (hs-cTnI) from bench to bedside, by application of a 3-step
      approach: validation in serum, correlation in plasma, and application on a
      clinical platform. METHODS: Patients without known CAD referred for rest/stress
      myocardial perfusion single-photon emission tomography/computer tomography (MPI
      SPECT/CT) were assigned to 3 consecutive cohorts: validation, correlation, and
      application. Functionally relevant CAD was adjudicated with the use of expert
      interpretation of MPI-SPECT/CT and, if available, coronary angiography. In the
      validation cohort resting hs-cTnI was measured in serum before stress testing
      with the research Erenna system, in serum and plasma in the correlation cohort
      with the research Erenna system, and in plasma in the application cohort with the
      clinical Clarity system. RESULTS: Overall, functionally relevant CAD was
      adjudicated in 21% (304/1478) of patients. In the validation cohort (n = 613), hs
      cTnI concentrations were significantly higher in patients with functionally
      relevant CAD (median 2.8 ng/L vs 1.9 ng/L, P < 0.001) as compared to patients
      without functionally relevant CAD and allowed a rule out with 95% sensitivity in
      14% of patients. In the correlation cohort (n = 606), hs-cTnI concentrations in
      serum and plasma strongly correlated (Spearman r = 0.921) and had similar
      diagnostic accuracy as quantified by the area under the receiver operating
      characteristic curve (0.686 vs 0.678, P = 0.425). In the application cohort (n =
      555), very low hs-cTnI plasma concentrations (< 0.5 ng/L) ruled out functionally
      relevant CAD with 95% sensitivity in 10% of patients. CONCLUSIONS: A single
      resting plasma hs-cTnI measurement can safely rule out functionally relevant CAD
      in around 10% of patients without known CAD.

PMID- 29038154
TI  - Deactivated CRISPR Associated Protein 9 for Minor-Allele Enrichment in Cell-Free
      DNA.
AB  - BACKGROUND: Cell-free DNA (cfDNA) diagnostics are emerging as a new paradigm of
      disease monitoring and therapy management. The clinical utility of these
      diagnostics is relatively limited by a low signal-to-noise ratio, such as with
      low allele frequency (AF) mutations in cancer. While enriching for rare alleles
      to increase their AF before sample analysis is one strategy that can greatly
      improve detection capability, current methods are limited in their
      generalizability, ease of use, and applicability to point mutations. METHODS:
      Leveraging the robust single-base-pair specificity and generalizability of the
      CRISPR associated protein 9 (Cas9) system, we developed a deactivated Cas9
      (dCas9)-based method of minor-allele enrichment capable of efficient single
      target and multiplexed enrichment. The dCas9 protein was complexed with single
      guide RNAs targeted to mutations of interest and incubated with cfDNA samples
      containing mutant strands at low abundance. Mutation-bound dCas9 complexes were
      isolated, dissociated, and the captured DNA purified for downstream use. RESULTS:
      Targeting the 3 most common epidermal growth factor receptor mutations (exon 19
      deletion, T790M, L858R) found in non-small cell lung cancer (NSCLC), we achieved
      >20-fold increases in AF and detected mutations by use of qPCR at an AF of 0.1%.
      In a cohort of 18 NSCLC patient-derived cfDNA samples, our method enabled
      detection of 8 out of 13 mutations that were otherwise undetected by qPCR.
      CONCLUSIONS: The dCas9 method provides an important application of the
      CRISPR/Cas9 system outside the realm of genome editing and can provide a step
      forward for the detection capability of cfDNA diagnostics.

PMID- 29038155
TI  - Objective Metabolomics Research.

PMID- 29038156
TI  - Human Toxicity Caused by Indole and Indazole Carboxylate Synthetic Cannabinoid
      Receptor Agonists: From Horizon Scanning to Notification.
AB  - BACKGROUND: The emergence of novel psychoactive substances (NPS), particularly
      synthetic cannabinoid receptor agonists (SCRA), has involved hundreds of
      potentially harmful chemicals in a highly dynamic international market
      challenging users', clinicians', and regulators' understanding of what
      circulating substances are causing harm. We describe a toxicovigilance system for
      NPS that predicted the UK emergence and identified the clinical toxicity caused
      by novel indole and indazole carboxylate SCRA. METHODS: To assist early accurate
      identification, we synthesized 5 examples of commercially unavailable indole and
      indazole carboxylate SCRA (FUB-NPB-22, 5F-NPB-22, 5F-SDB-005, FUB-PB-22, NM
      2201). We analyzed plasma and urine samples from 160 patients presenting to
      emergency departments with severe toxicity after suspected NPS use during 2015 to
      2016 for these and other NPS using data-independent LC-MS/MS. RESULTS: We
      successfully synthesized 5 carboxylate SCRAs using established synthetic and
      analytical chemistry methodologies. We identified at least 1 SCRA in samples from
      49 patients, including an indole or indazole carboxylate SCRA in 17 (35%),
      specifically 5F-PB-22 (14%), FUB PB-22 (6%), BB-22 (2%), 5F NPB-22 (20%), FUB NPB
      22 (2%), and 5F-SDB-005 (4%). In these 17 patients, there was analytical evidence
      of other substances in 16. Clinical features included agitation and aggression
      (82%), reduced consciousness (76%), acidosis (47%), hallucinations and paranoid
      features (41%), tachycardia (35%), hypertension (29%), raised creatine kinase
      (24%), and seizures (12%). CONCLUSIONS: This toxicovigilance system predicted the
      emergence of misuse of indole and indazole carboxylate SCRA, documented
      associated clinical harms, and notified relevant agencies. Toxicity appears
      consistent with other SCRA, including mental state disturbances and reduced
      consciousness.

PMID- 29038157
TI  - Increased Plasma Ferritin Concentration and Low-Grade Inflammation-A Mendelian
      Randomization Study.
AB  - BACKGROUND: It is unknown why increased plasma ferritin concentration predicts
      all-cause mortality. As low-grade inflammation and increased plasma ferritin
      concentration are associated with all-cause mortality, we hypothesized that
      increased plasma ferritin concentration is genetically associated with low-grade
      inflammation. METHODS: We investigated whether increased plasma ferritin
      concentration is associated with low-grade inflammation [i.e., increased
      concentrations of C-reactive protein (CRP) and complement component 3 (C3)] in
      62537 individuals from the Danish general population. We also applied a Mendelian
      randomization approach, using the hemochromatosis genotype C282Y/C282Y as an
      instrument for increased plasma ferritin concentration, to assess causality.
      RESULTS: For a doubling in plasma ferritin concentration, the odds ratio (95% CI)
      for CRP >=2 vs <2 mg/L was 1.12 (1.09-1.16), with a corresponding genetic
      estimate for C282Y/C282Y of 1.03 (1.01-1.06). For a doubling in plasma ferritin
      concentration, odds ratio (95% CI) for complement C3 >1.04 vs <=1.04 g/L was 1.28
      (1.21-1.35), and the corresponding genetic estimate for C282Y/C282Y was 1.06
      (1.03-1.12). Mediation analyses showed that 74% (95% CI, 24-123) of the
      association of C282Y/C282Y with risk of increased CRP and 56% (17%-96%) of the
      association of C282Y/C282Y with risk of increased complement C3 were mediated
      through plasma ferritin concentration. CONCLUSIONS: Increased plasma ferritin
      concentration as a marker of increased iron concentration is associated
      observationally and genetically with low-grade inflammation, possibly indicating
      a causal relationship from increased ferritin to inflammation. However, as HFE
      may also play an immunological role indicating pleiotropy and as incomplete
      penetrance of C282Y/C282Y indicates buffering mechanisms, these weaknesses in the
      study design could bias the genetic estimates.

PMID- 29038158
TI  - Activation of Human Transient Receptor Potential Melastatin-8 (TRPM8) by Calcium
      Rich Particulate Materials and Effects on Human Lung Cells.
AB  - To better understand how adverse health effects are caused by exposure to
      particulate materials, and to develop preventative measures, it is important to
      identify the properties of particles and molecular targets that link exposure
      with specific biologic outcomes. Coal fly ash (CFA) is a by-product of coal
      combustion that can affect human health. We report that human transient receptor
      potential melastatin-8 (TRPM8) and an N-terminally truncated TRPM8 variant (TRPM8
      Delta801) are activated by CFA and calcium-rich nanoparticles and/or soluble
      salts within CFA. TRPM8 activation by CFA was potentiated by cold temperature
      involving the phosphatidylinositol 4,5-bisphosphate binding residue (L1008), but
      was independent of the icilin and menthol binding site residue Y745 and,
      essentially, the N-terminal amino acids 1-800. CFA, calcium nanoparticles, and
      calcium salts also activated transient receptor potential vanilloid-1 (TRPV1) and
      transient receptor potential ankyrin-1 (TRPA1), but not TRPV4. CFA treatment
      induced CXCL1 and interleukin-8 mRNA in BEAS-2B and primary human bronchial
      epithelial cells through activation of both TRPM8 and TRPV1. However, neither
      mouse nor rat TRPM8 was activated by these materials, and Trpm8 knockout had no
      effect on cytokine induction in the lungs of CFA-instilled mice. Amino acids S921
      and S927 in mouse Trpm8 were identified as important for the lack of response to
      CFA. These results imply that TRPM8, in conjunction with TRPV1 and TRPA1, might
      sense selected forms of inhaled particulate materials in human airways, shaping
      cellular responses to these materials, and improving our understanding of how and
      why certain particulate materials elicit different responses in biologic systems,
      affecting human health.

PMID- 29038159
TI  - Loss of Extracellular Signal-Regulated Kinase 1/2 in the Retinal Pigment
      Epithelium Leads to RPE65 Decrease and Retinal Degeneration.
AB  - Recent work suggested that the activity of extracellular signal-regulated kinase
      1/2 (ERK1/2) is increased in the retinal pigment epithelium (RPE) of age-related
      macular degeneration (ARMD) patients and therefore could be an attractive
      therapeutic target. Notably, ERK1/2 pathway inhibitors are used in cancer
      therapy, with severe and noncharacterized ocular side effects. To decipher the
      role of ERK1/2 in RPE cells, we conditionally disrupted the Erk1 and Erk2 genes
      in mouse RPE. The loss of ERK1/2 activity resulted in a significant decrease in
      the level of RPE65 expression, a decrease in ocular retinoid levels concomitant
      with low visual function, and a rapid disorganization of RPE cells, ultimately
      leading to retinal degeneration. Our results identify the ERK1/2 pathway as a
      direct regulator of the visual cycle and a critical component of the viability of
      RPE and photoreceptor cells. Moreover, our results caution about the need for a
      very fine adjustment of kinase inhibition in cancer or ARMD treatment in order to
      avoid ocular side effects.

PMID- 29038160
TI  - A High-Resolution Genome-Wide CRISPR/Cas9 Viability Screen Reveals Structural
      Features and Contextual Diversity of the Human Cell-Essential Proteome.
AB  - To interrogate genes essential for cell growth, proliferation and survival in
      human cells, we carried out a genome-wide clustered regularly interspaced short
      palindromic repeat (CRISPR)/Cas9 screen in a B-cell lymphoma line using a custom
      extended-knockout (EKO) library of 278,754 single-guide RNAs (sgRNAs) that
      targeted 19,084 RefSeq genes, 20,852 alternatively spliced exons, and 3,872
      hypothetical genes. A new statistical analysis tool called robust analytics and
      normalization for knockout screens (RANKS) identified 2,280 essential genes, 234
      of which were unique. Individual essential genes were validated experimentally
      and linked to ribosome biogenesis and stress responses. Essential genes exhibited
      a bimodal distribution across 10 different cell lines, consistent with a
      continuous variation in essentiality as a function of cell type. Genes essential
      in more lines had more severe fitness defects and encoded the evolutionarily
      conserved structural cores of protein complexes, whereas genes essential in fewer
      lines formed context-specific modules and encoded subunits at the periphery of
      essential complexes. The essentiality of individual protein residues across the
      proteome correlated with evolutionary conservation, structural burial, modular
      domains, and protein interaction interfaces. Many alternatively spliced exons in
      essential genes were dispensable and were enriched for disordered regions.
      Fitness defects were observed for 44 newly evolved hypothetical reading frames.
      These results illuminate the contextual nature and evolution of essential gene
      functions in human cells.

PMID- 29038161
TI  - Mechanistic Differences in Transcription Initiation at TATA-Less and TATA
      Containing Promoters.
AB  - A yeast in vitro system was developed that is active for transcription at both
      TATA-containing and TATA-less promoters. Transcription with extracts made from
      cells depleted of TFIID subunit Taf1 demonstrated that promoters of both classes
      are TFIID dependent, in agreement with recent in vivo findings. TFIID depletion
      can be complemented in vitro by additional recombinant TATA binding protein (TBP)
      at only the TATA-containing promoters. In contrast, high levels of TBP did not
      complement Taf1 depletion in vivo and instead repressed transcription from both
      promoter types. We also demonstrate the importance of the TATA-like sequence
      found at many TATA-less promoters and describe how the presence or absence of the
      TATA element is likely not the only feature that distinguishes these two types of
      promoters.

PMID- 29038162
TI  - Systematic analysis of human cells lacking ATG8 proteins uncovers roles for
      GABARAPs and the CCZ1/MON1 regulator C18orf8/RMC1 in macro and selective
      autophagic flux.
AB  - Selective and macro autophagy sequester specific organelles/substrates or bulk
      cytoplasm, respectively, inside autophagosomes as cargo for delivery to
      lysosomes. The mammalian ATG8 orthologues (MAP1LC3A/B/C and GABARAP/L1/L2) are
      ubiquitin (UB)-like proteins conjugated to the autophagosome membrane and are
      thought to facilitate cargo receptor recruitment, vesicle maturation, and
      lysosomal fusion. To elucidate the molecular functions of the ATG8 proteins, we
      engineered cells lacking genes for each subfamily as well as all six mammalian
      ATG8s. Loss of GABARAPs alone attenuates autophagic flux basally and in response
      to macro or selective autophagic stimuli including PARKIN-dependent mitophagy,
      and cells lacking all ATG8 proteins accumulate cytoplasmic UB aggregates, which
      are resolved following ectopic expression of individual GABARAPs. Autophagosomes
      from cells lacking GABARAPs had reduced lysosomal content by quantitative
      proteomics, consistent with fusion defects, but accumulated regulators of late
      endosome (LE)/autophagosome maturation. Through interaction proteomics of
      proteins accumulating in GABARAP/L1/L2-deficient cells, we identified
      C18orf8/RMC1 as a new subunit of the CCZ1-MON1 RAB7 guanine exchange factor (GEF)
      that positively regulates RAB7 recruitment to LE/autophagosomes. This work
      defines unique roles for GABARAP and LC3 subfamilies in macro and selective
      autophagy and demonstrates how analysis of autophagic machinery in the absence of
      flux can identify new regulatory circuits.

PMID- 29038163
TI  - Corrected and Republished from: BCL11A Is a Critical Component of a
      Transcriptional Network That Activates RAG Expression and V(D)J Recombination.
AB  - Recombination activating gene 1 (RAG1) and RAG2 are critical enzymes for
      initiating variable-diversity-joining [V(D)J] segment recombination, an essential
      process for antigen receptor expression and lymphocyte development. The BCL11A
      transcription factor is required for B cell and plasmacytoid dendritic cell (pDC)
      development, but its molecular function(s) in early B cell fate specification and
      commitment is unknown. We show here that the major B cell isoform, BCL11A-XL,
      binds directly to the RAG1 promoter as well as directly to regulatory regions of
      transcription factors previously implicated in both B cell and pDC development to
      activate RAG1 and RAG2 gene transcription in pro- and pre-B cells. We employed
      BCL11A overexpression with recombination substrates to demonstrate direct
      consequences of BCL11A/RAG modulation on V(D)J recombination. We conclude that
      BCL11A is a critical component of a transcriptional network that regulates B cell
      fate by controlling V(D)J recombination.

PMID- 29038165
TI  - Authors' reply to Baker and Alderson.

PMID- 29038166
TI  - Why and how to step down chronic asthma drugs.
AB  - Asthma is a common chronic airways disease. The goal of asthma management is to
      control symptoms while minimizing the side effects of treatment. Following a
      period of stable asthma, clinicians should consider stepping down treatment. This
      approach is recommended by current guidelines. Step-down has been studied for
      several types of asthma drug regimens, and certain approaches may have lower risk
      than others. Systematic reviews of multiple trials support the following specific
      step-down approaches: optimizing inhaled corticosteroid dosing when stepping down
      oral corticosteroid, reducing inhaled corticosteroid from a higher dose, lowering
      inhaled corticosteroid-long acting bronchodilator (ICS-LABA) dose while adding
      ICS-LABA on-demand, adding leukotriene receptor antagonist (LTRA) while lowering
      inhaled corticosteroid dose, and using allergen immunotherapy when reducing
      inhaled corticosteroid from a higher dose. Systematic reviews of multiple trials
      support an increased risk of asthma exacerbation for patients who completely stop
      taking inhaled corticosteroid or long acting bronchodilator. Strategies to
      implement step-down in practice include the use of risk prediction as well as
      tools to support shared decision making and communication about risk between
      clinicians and patients.

PMID- 29038164
TI  - Protein Kinase A/CREB Signaling Prevents Adriamycin-Induced Podocyte Apoptosis
      via Upregulation of Mitochondrial Respiratory Chain Complexes.
AB  - Previous work showed that the activation of protein kinase A (PKA) signaling
      promoted mitochondrial fusion and prevented podocyte apoptosis. The cAMP response
      element binding protein (CREB) is the main downstream transcription factor of PKA
      signaling. Here we show that the PKA agonist 8-(4-chlorophenylthio)adenosine
      3',5'-cyclic monophosphate-cyclic AMP (pCPT-cAMP) prevented the production of
      adriamycin (ADR)-induced reactive oxygen species and apoptosis in podocytes,
      which were inhibited by CREB RNA interference (RNAi). The activation of PKA
      enhanced mitochondrial function and prevented the ADR-induced decrease of
      mitochondrial respiratory chain complex I subunits, NADH-ubiquinone
      oxidoreductase complex (ND) 1/3/4 genes, and protein expression. Inhibition of
      CREB expression alleviated pCPT-cAMP-induced ND3, but not the recovery of ND1/4
      protein, in ADR-treated podocytes. In addition, CREB RNAi blocked the pCPT-cAMP
      induced increase in ATP and the expression of peroxisome proliferator-activated
      receptor gamma coactivator 1 alpha (PGC1-alpha). The chromatin
      immunoprecipitation assay showed enrichment of CREB on PGC1-alpha and ND3
      promoters, suggesting that these promoters are CREB targets. In vivo, both an
      endogenous cAMP activator (isoproterenol) and pCPT-cAMP decreased the
      albumin/creatinine ratio in mice with ADR nephropathy, reduced glomerular
      oxidative stress, and retained Wilm's tumor suppressor gene 1 (WT-1)-positive
      cells in glomeruli. We conclude that the upregulation of mitochondrial
      respiratory chain proteins played a partial role in the protection of PKA/CREB
      signaling.

PMID- 29038168
TI  - Fasting Versus Nonfasting and Low-Density Lipoprotein Cholesterol Accuracy.
AB  - BACKGROUND: Recent recommendations favoring nonfasting lipid assessment may
      affect low-density lipoprotein cholesterol (LDL-C) estimation. The novel method
      of LDL-C estimation (LDL-CN) uses a flexible approach to derive patient-specific
      ratios of triglycerides to very low-density lipoprotein cholesterol. This
      adaptability may confer an accuracy advantage in nonfasting patients over the
      fixed approach of the classic Friedewald method (LDL-CF). METHODS: We used a US
      cross-sectional sample of 1 545  634 patients (959 153 fasting >=10-12 hours; 586
      481 nonfasting) from the second harvest of the Very Large Database of Lipids
      study to assess for the first time the impact of fasting status on novel LDL-C
      accuracy. Rapid ultracentrifugation was used to directly measure LDL-C content
      (LDL-CD). Accuracy was defined as the percentage of LDL-CD falling within an
      estimated LDL-C (LDL-CN or LDL-CF) category by clinical cut points. For low
      estimated LDL-C (<70 mg/dL), we evaluated accuracy by triglyceride levels. The
      magnitude of absolute and percent differences between LDL-CD and estimated LDL-C
      (LDL-CN or LDL-CF) was stratified by LDL-C and triglyceride categories. RESULTS:
      In both fasting and nonfasting samples, accuracy was higher with the novel method
      across all clinical LDL-C categories (range, 87%-94%) compared with the
      Friedewald estimation (range, 71%-93%; P<=0.001). With LDL-C <70 mg/dL,
      nonfasting LDL-CN accuracy (92%) was superior to LDL-CF accuracy (71%; P<0.001).
      In this LDL-C range, 19% of fasting and 30% of nonfasting patients had
      differences >=10 mg/dL between LDL-CF and LDL-CD, whereas only 2% and 3% of
      patients, respectively, had similar differences with novel estimation. Accuracy
      of LDL-C <70 mg/dL further decreased as triglycerides increased, particularly for
      Friedewald estimation (range, 37%-96%) versus the novel method (range, 82%-94%).
      With triglycerides of 200 to 399 mg/dL in nonfasting patients, LDL-CN <70 mg/dL
      accuracy (82%) was superior to LDL-CF (37%; P<0.001). In this triglyceride range,
      73% of fasting and 81% of nonfasting patients had >=10 mg/dL differences between
      LDL-CF and LDL-CD compared with 25% and 20% of patients, respectively, with LDL
      CN. CONCLUSIONS: Novel adaptable LDL-C estimation performs better in nonfasting
      samples than the fixed Friedewald estimation, with a particular accuracy
      advantage in settings of low LDL-C and high triglycerides. In addition to
      stimulating further study, these results may have immediate relevance for
      guideline committees, laboratory leadership, clinicians, and patients. CLINICAL
      TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier:
      NCT01698489.

PMID- 29038167
TI  - Sex Differences and Similarities in Atrial Fibrillation Epidemiology, Risk
      Factors, and Mortality in Community Cohorts: Results From the BiomarCaRE
      Consortium (Biomarker for Cardiovascular Risk Assessment in Europe).
AB  - BACKGROUND: Atrial fibrillation (AF) is a common cardiac disease in aging
      populations with high comorbidity and mortality. Sex differences in AF
      epidemiology are insufficiently understood. METHODS: In N=79 793 individuals
      without AF diagnosis at baseline (median age, 49.6 years; age range, 24.1-97.6
      years; 51.7% women) from 4 community-based European studies (FINRISK, DanMONICA,
      Moli-sani Northern Sweden) of the BiomarCaRE consortium (Biomarker for
      Cardiovascular Risk Assessment in Europe), we examined AF incidence, its
      association with mortality, common risk factors, biomarkers, and prevalent
      cardiovascular disease, and their attributable risk by sex. Median follow-up time
      was 12.6 (to a maximum of 28.2) years. RESULTS: Fewer AF cases were observed in
      women (N=1796; 4.4%), than in men (N=2465; 6.4%). Cardiovascular risk factor
      distribution and lipid profile at baseline were less beneficial in men than in
      women, and cardiovascular disease was more prevalent in men. Cumulative incidence
      increased markedly after the age of 50 years in men and after 60 years in women.
      The lifetime risk was similar (>30%) for both sexes. Subjects with incident AF
      had a 3.5-fold risk of death in comparison with those without AF. Multivariable
      adjusted models showed sex differences for the association of body mass index and
      AF (hazard ratio per standard deviation increase, 1.18; 95% confidence interval
      [CI], 1.12-1.23 in women versus 1.31; 95% CI 1.25-1.38 in men; interaction P
      value of 0.001). Total cholesterol was inversely associated with incident AF with
      a greater risk reduction in women (hazard ratio per SD, 0.86; 95% CI, 0.81-0.90
      versus 0.92; 95% CI, 0.88-0.97 in men; interaction P value of 0.023). No sex
      differences were seen for C-reactive protein and N-terminal pro B-type
      natriuretic peptide. The population-attributable risk of all risk factors
      combined was 41.9% in women and 46.0% in men. About 20% of the risk was observed
      for body mass index. CONCLUSIONS: Lifetime risk of AF was high, and AF was
      strongly associated with increased mortality both in women and men. Body mass
      index explained the largest proportion of AF risk. Observed sex differences in
      the association of body mass index and total cholesterol with AF need to be
      evaluated for underlying pathophysiology and relevance to sex-specific prevention
      strategies.

PMID- 29038169
TI  - Low-Dose Exposure to Ionizing Radiation Deregulates the Brain-Specific MicroRNA
      134 in Interventional Cardiologists.

PMID- 29038171
TI  - Margaret McCartney: Hydration, common sense, and evidence.

PMID- 29038170
TI  - Dissecting Nucleosome Function with a Comprehensive Histone H2A and H2B Mutant
      Library.
AB  - Using a comprehensive library of histone H2A and H2B mutants, we assessed the
      biological function of each amino acid residue involved in various stress
      conditions including exposure to different DNA damage-inducing reagents,
      different growth temperatures, and other chemicals. H2B N- and H2A C-termini were
      critical for maintaining nucleosome function and mutations in these regions led
      to pleiotropic phenotypes. Additionally, two screens were performed using this
      library, monitoring heterochromatin gene silencing and genome stability, to
      identify residues that could compromise normal function when mutated. Many
      distinctive regions within the nucleosome were revealed. Furthermore, we used the
      barcode sequencing (bar-seq) method to profile the mutant composition of many
      libraries in one high-throughput sequencing experiment, greatly reducing the
      labor and increasing the capacity. This study not only demonstrates the
      applications of the versatile histone library, but also reveals many previously
      unknown functions of histone H2A and H2B.

PMID- 29038172
TI  - Precision Medicine for Cardiac Resynchronization: Predicting Quality of Life
      Benefits for Individual Patients-An Analysis From 5 Clinical Trials.
AB  - BACKGROUND: Clinical trials have established the average benefit of cardiac
      resynchronization therapy (CRT), but estimating benefit for individual patients
      remains difficult because of the heterogeneity in treatment response.
      Accordingly, we created a multivariable model to predict changes in quality of
      life (QoL) with and without CRT. METHODS AND RESULTS: Patient-level data from 5
      randomized trials comparing CRT with no CRT were used to create a prediction
      model of change in QoL at 3 months using a partial proportional odds model for no
      change, small, moderate, and large improvement, or deterioration of any
      magnitude. The C statistics for not worsening or obtaining at least a small,
      moderate, and large improvement were calculated. Among the 3614 patients,
      regardless of assigned treatment, 33.3% had a deterioration in QoL, 9.2% had no
      change, 9.2% had a small improvement, 13.5% had a moderate improvement, and the
      remaining 34.9% had a large improvement. Patients undergoing CRT were less likely
      to have a decrement in their QoL (28.2% versus 38.9%; P<0.001) and more likely to
      have a large QoL improvement (38.7% versus 30.6%; P<0.001). A partial
      proportional odds model identified baseline QoL, age, and an interaction of CRT
      with QRS duration as predictors of QoL benefits 3 months after randomization. C
      statistics of 0.65 for not worsening, 0.68 for at least a small improvement, 0.69
      for at least a moderate improvement, and 0.73 for predicting a large improvement
      were observed. CONCLUSIONS: There is marked heterogeneity of treatment benefit of
      CRT that can be predicted based on baseline QoL, age, and QRS duration.

PMID- 29038173
TI  - Combinatorial regulation of the balance between dynein microtubule end
      accumulation and initiation of directed motility.
AB  - Cytoplasmic dynein is involved in a multitude of essential cellular functions.
      Dynein's activity is controlled by the combinatorial action of several regulatory
      proteins. The molecular mechanism of this regulation is still poorly understood.
      Using purified proteins, we reconstitute the regulation of the human dynein
      complex by three prominent regulators on dynamic microtubules in the presence of
      end binding proteins (EBs). We find that dynein can be in biochemically and
      functionally distinct pools: either tracking dynamic microtubule plus-ends in an
      EB-dependent manner or moving processively towards minus ends in an adaptor
      protein-dependent manner. Whereas both dynein pools share the dynactin complex,
      they have opposite preferences for binding other regulators, either the adaptor
      protein Bicaudal-D2 (BicD2) or the multifunctional regulator Lissencephaly-1
      (Lis1). BicD2 and Lis1 together control the overall efficiency of motility
      initiation. Remarkably, dynactin can bias motility initiation locally from
      microtubule plus ends by autonomous plus-end recognition. This bias is further
      enhanced by EBs and Lis1. Our study provides insight into the mechanism of dynein
      regulation by dissecting the distinct functional contributions of the individual
      members of a dynein regulatory network.

PMID- 29038174
TI  - Tumor-associated macrophages (TAMs) depend on ZEB1 for their cancer-promoting
      roles.
AB  - Accumulation of tumor-associated macrophages (TAMs) associates with malignant
      progression in cancer. However, the mechanisms that drive the pro-tumor functions
      of TAMs are not fully understood. ZEB1 is best known for driving an epithelial-to
      mesenchymal transition (EMT) in cancer cells to promote tumor progression.
      However, a role for ZEB1 in macrophages and TAMs has not been studied. Here we
      describe that TAMs require ZEB1 for their tumor-promoting and chemotherapy
      resistance functions in a mouse model of ovarian cancer. Only TAMs that expressed
      full levels of Zeb1 accelerated tumor growth. Mechanistically, ZEB1 expression in
      TAMs induced their polarization toward an F4/80low pro-tumor phenotype, including
      direct activation of Ccr2 In turn, expression of ZEB1 by TAMs induced Ccl2, Cd74,
      and a mesenchymal/stem-like phenotype in cancer cells. In human ovarian
      carcinomas, TAM infiltration and CCR2 expression correlated with ZEB1 in tumor
      cells, where along with CCL2 and CD74 determined poorer prognosis. Importantly,
      ZEB1 in TAMs was a factor of poorer survival in human ovarian carcinomas. These
      data establish ZEB1 as a key factor in the tumor microenvironment and for
      maintaining TAMs' tumor-promoting functions.

PMID- 29038175
TI  - Predictability of Recurrence using Immunohistochemistry to delineate Surgical
      Margins in mucosal Head and Neck Squamous Cell Carcinoma (PRISM-HNSCC): study
      protocol for a prospective, observational and bilateral study in Australia and
      India.
AB  - OBJECTIVES: Treatment failure and poor 5-year survival in mucosal head and neck
      squamous cell carcinoma (HNSCC) has remained unchanged for decades mainly due to
      advanced stage of presentation and high rates of recurrence. Incomplete surgical
      removal of the tumour, attributed to lack of reliable methods to delineate the
      surgical margins, is a major cause of disease recurrence. The predictability of
      recurrence using immunohistochemistry (IHC) to delineate surgical margins (PRISM)
      in mucosal HNSCC study aims to redefine margin status by identifying the true
      extent of the tumour at the molecular level by performing IHC with molecular
      markers, eukaryotic initiation factor, eIF4Eand tumour suppressor gene, p53, on
      the surgical margins and test the use of Lugol's iodine and fluorescence
      visualisation prior to the wide local excision. This article describes the study
      protocol at its pre - results stage. METHODS AND ANALYSIS: PRISM-HNSCC is a
      bilateral observational research being conducted in Darwin, Australia and
      Vellore, India. Individuals diagnosed with HNSCC will undergo the routine wide
      local excision of the tumour followed by histopathological assessment. Tumours
      with clear surgical margins that satisfy the exclusion criteria will be selected
      for further staining of the margins with eIF4E and p53 antibodies. Results of IHC
      staining will be correlated with recurrences in an attempt to predict the risk of
      disease recurrence. Patients in Darwin will undergo intraoperative staining of
      the lesion with Lugol's iodine and fluorescence visualisation to delineate the
      excision margins while patients in Vellore will not undertake these tests. The
      outcomes will be analysed. ETHICS AND DISSEMINATION: The PRISM-HNSCC study was
      approved by the institutional ethics committees in Darwin (Human Research Ethics
      Committee 13-2036) and Vellore (Institutional Review Board Min. no. 8967).
      Outcomes will be disseminated through publications in academic journals and
      presentations at educational meetings and conferences. It will be presented as
      dissertation at the Charles Darwin University. We will communicate the study
      results to both participating sites. Participating sites will communicate results
      with patients who have indicated an interest in knowing the results. TRIAL
      REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry
      (ACTRN12616000715471).

PMID- 29038176
TI  - Maternal body mass index and the prevalence of spontaneous and elective preterm
      deliveries in an Irish obstetric population: a retrospective cohort study.
AB  - OBJECTIVE: To estimate the association between maternal body mass index (BMI) and
      risk of spontaneous preterm delivery (sPTD) and elective preterm delivery (ePTD)
      in singleton and multiple pregnancies. DESIGN: Retrospective cohort study.
      SETTING: Electronic records of all deliveries from 2009 through 2013 in a
      tertiary university hospital were abstracted for demographic and obstetrical
      information. PARTICIPANTS: A total of 38 528 deliveries were included.
      Participants with missing data were excluded from the study. BMI was calculated
      from the measurement of height and weight at the first prenatal visit and
      categorised. Sonographic confirmation of gestational age was standard. OUTCOME
      MEASURES: Primary outcomes, sPTD and ePTD in singleton and multiple pregnancies,
      were evaluated by multinomial logistic regression analyses, stratified by parity,
      controlling for confounding variables. RESULTS: Overall rate of PTD was 5.9%,
      from which 2.7% were sPTD and 3.2% ePTD. The rate of PTD was 50.4% in multiple
      pregnancies and 5.0% in singleton pregnancies. The risk of sPTD was increased in
      obese nulliparas (adjusted OR (aOR) 2.8, 95% CI 1.7 to 4.4) and underweight
      multiparas (aOR 2.2, 95% CI 1.3 to 3.8). The risk of ePTD was increased in
      underweight nulliparas (aOR 1.8; 95% CI 1.04 to 3.4) and severely obese
      multiparas (aOR 1.4, 95% CI 1.02 to 3.8).Severe obesity increased the risk of
      both sPTD (aOR 1.4; 95% CI 1.01 to 2.1) and ePTD (aOR 1.4; 95% CI 1.1 to 1.8) in
      singleton pregnancies. Obesity did not influence the rate of either sPTD or ePTD
      in multiple pregnancies. CONCLUSION: Maternal obesity is an independent risk
      factor for PTD in singleton pregnancies but not in multiple pregnancies. Obesity
      and nulliparity increase the risk of sPTD, whereas obesity and multiparity
      increase the risk of ePTD.

PMID- 29038177
TI  - Cervical and breast cancer screening participation and utilisation of maternal
      health services: a cross-sectional study among immigrant women in Southern Italy.
AB  - OBJECTIVES: Women make up approximately half of the world's one billion migrants.
      Immigrant women tend to be one of the most vulnerable population groups with
      respect to healthcare. Cancer screening (CS) and maternal and reproductive health
      have been included among the 10 main issues pertinent to women's health. The aim
      of this study is to explore breast and cervical CS participation and to acquire
      information regarding access to healthcare services during pregnancy, childbirth
      and the postpartum period among age eligible immigrant women in Southern Italy.
      METHODS: A structured questionnaire was used to collect data from each
      participant. Women aged 25-64 years who had not had a hysterectomy and women aged
      50-69 years without history of breast cancer were considered eligible for the
      evaluation of cervical and breast CS participation, respectively. Moreover, women
      who had delivered at least once in Italy were enrolled to describe antenatal and
      postpartum care services use. All women were recruited through the third sector
      and non-profit organisations (NPOs). RESULTS: Rate of cervical CS among the 419
      eligible women was low (39.1%), and about one-third had had a Pap test for
      screening purposes within a 3-year period from interview (32.8%). Regarding
      breast CS practices, of the 125 eligible women 45.6% had had a mammography for
      control purposes and less than a quarter (26, 20.8%) had their mammography within
      the recommended time interval of 2 years. About 80% of the respondents did not
      report difficulties of access and use of antenatal and postpartum services.
      CONCLUSION: This study provides currently unavailable information about adherence
      to CS and maternal and child health that could encourage future research to
      develop and test culturally appropriate, women-centred strategies for promoting
      timely and regular CS among immigrant women in Italy.

PMID- 29038178
TI  - Early sexual experiences of teenage heterosexual males in Australia: a cross
      sectional survey.
AB  - OBJECTIVE: There are limited data on the patterns of early sexual behaviours
      among Australian teenage heterosexual boys. This study describes the nature and
      onset of early sexual experiences in this population through a cross-sectional
      survey. DESIGN: A cross-sectional survey between 2014 and 2015 SETTING: Major
      sexual health clinics and community sources across Australia PARTICIPANTS:
      Heterosexual men aged 17-19 years RESULTS: There were 191 men in the study with a
      median age of 19.1 years. Median age at first oral sex was 16.4 years (IQR: 15.5
      17.7) and 16.9 years (IQR: 16.0-18.0) for first vaginal sex. Most men had engaged
      in oral sex (89.5%) and vaginal sex (91.6%) in the previous 12 months with 32.6%
      reporting condom use at last vaginal sex. Of the total lifetime female partners
      for vaginal sex reported by men as a group (n=1187): 54.3% (n=645) were the same
      age as the man, 28.3% (n=336) were a year or more younger and 17.4% (n=206) were
      a year or more older. Prior anal sex with females was reported by 22% with 47%
      reporting condom use at last anal sex. Median age at first anal sex was 18.2
      years (IQR: 17.3-18.8). Anal sex with a female was associated with having five or
      more lifetime female sexual partners for oral and vaginal sex. CONCLUSIONS: These
      data provide insights into the trajectory of sexual behaviours experienced by
      teenage heterosexual boys following sexual debut, findings which can inform
      programme promoting sexual health among teenage boys.

PMID- 29038179
TI  - Effects of school-based intervention by emergency medical technicians on students
      and their parents: a community-based prospective study of the Akashi project.
AB  - OBJECTIVE: Stroke lessons for youth provided by emergency medical technicians
      (EMTs) may be an effective strategy to facilitate early intervention for patients
      with stroke. The aim of this study was to examine how effective EMT-led lessons
      on stroke awareness for schoolchildren were at disseminating stroke information.
      SETTING, PARTICIPANTS AND OUTCOME MEASURES: The study was performed in the city
      of Akashi, Hyogo, Japan (Akashi project). Children (aged 9-10 years old) at 11
      public elementary schools and their parents were enrolled in this study. EMTs
      from the firefighting headquarters provided lessons on stroke to the children
      using our educational materials between September 2014 and October 2015. Each
      child was given our educational materials to take home and discuss stroke with
      their parents. The children and their parents answered questionnaires on stroke
      knowledge before, immediately and at 3 months after the lesson. RESULTS: A total
      of 763 children and 489 parents were enrolled (ie, 64% of children). The scores
      of either stroke symptoms or risk factors were significantly higher immediately
      and at 3 months after the lesson, compared with before the lesson, both in
      children and the parents (p<0.01). Compared with the baseline in both groups (58%
      in children, 83% in parents), the meaning of the FAST mnemonic at 3 months (88%,
      94%), as well as at immediately after the lesson (90%, 89%), was significantly
      higher (p<0.001). CONCLUSION: Stroke education by EMTs was effective in
      increasing stroke awareness in elementary school children, as well as their
      parents.

PMID- 29038180
TI  - Appropriateness of cases presenting in the emergency department following
      ambulance service secondary telephone triage: a retrospective cohort study.
AB  - OBJECTIVE: To investigate the appropriateness of cases presenting to the
      emergency department (ED) following ambulance-based secondary telephone triage.
      DESIGN: A pragmatic retrospective cohort analysis of all the planned and
      unplanned ED presentations within 48 hours of a secondary telephone triage.
      SETTING: The secondary telephone triage service, called the Referral Service, and
      the hospitals were located in metropolitan Melbourne, Australia and operated 24
      hours a day, servicing 4.25 million people. The Referral Service provides an in
      depth secondary triage of cases classified as low acuity when calling the
      Australian emergency telephone number. POPULATION: Cases triaged by the Referral
      Service between September 2009 and June 2012 were linked to ED and hospital
      admission records (N=44,523). Planned ED presentations were cases referred to the
      ED following the secondary triage, unplanned ED presentations were cases that
      presented despite being referred to alternative care pathways. MAIN OUTCOME
      MEASURES: Appropriateness was measured using an ED suitability definition and
      hospital admission rates. These were compared with mean population data which
      consisted of all of the ED presentations for the state (termed the 'average
      Victorian ED presentation'). RESULTS: Planned ED presentations were more likely
      to be ED suitable than unplanned ED presentations (OR 1.62; 95% CI 1.5 to 1.7;
      p<0.001) and the average Victorian ED presentation (OR 1.85; 95% CI 1.01 to 3.4;
      p=0.046). They were also more likely to be admitted to the hospital than the
      unplanned ED presentation (OR 1.5; 95% CI 1.4 to 1.6; p<0.001) and the average
      Victorian ED presentation (OR 2.3, 95% CI 2.24 to 2.33; p<0.001). Just under 15%
      of cases diverted away from the emergency care pathways presented in the ED
      (unplanned ED attendances), and 9.5% of all the alternative care pathway cases
      were classified as ED suitable and 6.5% were admitted to hospital. CONCLUSIONS:
      Secondary telephone triage was able to appropriately identify many ED suitable
      cases, and while most cases referred to alternative care pathways did not present
      in the ED. Further research is required to establish that these were not
      inappropriately triaged away from the emergency care pathways.

PMID- 29038181
TI  - Barriers and facilitators to healthy lifestyle and acceptability of a dietary and
      physical activity intervention among African Caribbean prostate cancer survivors
      in the UK: a qualitative study.
AB  - OBJECTIVES: Diet and lifestyle may have a role in delaying prostate cancer
      progression, but little is known about the health behaviours of Black British
      prostate cancer survivors despite this group having a higher prostate cancer
      mortality rate than their White counterparts. We explored the barriers and
      facilitators to dietary and lifestyle changes and the acceptability of a diet and
      physical activity intervention in African Caribbean prostate cancer survivors.
      DESIGN: We conducted semistructured in-depth interviews and used thematic
      analysis to code and group the data. PARTICIPANTS AND SETTING: We recruited 14
      African Caribbean prostate cancer survivors via letter or at oncology follow-up
      appointments using purposive and convenience sampling. RESULTS: A prostate cancer
      diagnosis did not trigger dietary and lifestyle changes in most men. This lack of
      change was underpinned by five themes: precancer diet and lifestyle, evidence,
      coping with prostate cancer, ageing, and autonomy. Men perceived their diet and
      lifestyle to be healthy and were uncertain about the therapeutic benefits of
      these factors on prostate cancer recurrence. They considered a lifestyle
      intervention as unnecessary because their prostate-specific antigen (PSA) level
      was kept under control by the treatments they had received. They believed dietary
      and lifestyle changes should be self-initiated and motivated, but were willing to
      make additional changes if they were perceived to be beneficial to health.
      Nonetheless, some men cited advice from health professionals and social support
      in coping with prostate cancer as facilitators to positive dietary and lifestyle
      changes. A prostate cancer diagnosis and ageing also heightened men's awareness
      of their health, particularly in regards to their body weight. CONCLUSIONS: A
      dietary and physical activity intervention framed as helping men to regain
      fitness and aid post-treatment recovery aimed at men with elevated PSA may be
      appealing and acceptable to African Caribbean prostate cancer survivors.

PMID- 29038182
TI  - Protocol for a scoping review to identify and map the global health personnel
      considered skilled attendants at birth in low and middle-income countries between
      2000 and 2015.
AB  - INTRODUCTION: Despite progress towards the Millennium Development Goals (MDG),
      maternal mortality remains high in countries where there are shortages of skilled
      personnel able to manage and provide quality care during pregnancy and
      childbirth. The 'percentage of births attended by skilled health personnel' (SAB,
      skilled attendants at birth) was a key indicator for tracking progress since the
      MDGs and is part of the Sustainable Development Goal agenda. However, due to
      contextual differences between and within countries on the definition of SAB, a
      lack of clarity exists around the training, competencies, and skills they are
      qualified to perform. In this paper, we outline a scoping review protocol that
      poses to identify and map the health personnel considered SAB in low and middle
      income countries (LMIC). METHODS AND ANALYSIS: A search will be conducted for the
      years 2000-2015 in PubMed/MEDLINE, EMBASE, CINAHL Complete, Cochrane Database of
      Systematic Reviews, POPLINE and the WHO Global Health Library. A manual search of
      reference lists from identified studies or systematic reviews and a hand search
      of the literature from international partner organisations will be done. Original
      studies conducted in LMIC that assessed health personnel (paid or voluntary)
      providing interventions during the intrapartum period will be considered for
      inclusion. ETHICS AND DISSEMINATION: A scoping review is a secondary analysis of
      published literature and does not require ethics approval. This scoping review
      proposes to synthesise data on the training, competency and skills of identified
      SAB and expands on other efforts to describe this global health workforce. The
      results will inform recommendations around improved coverage measurement and
      reporting of SAB moving forward, allowing for more accurate, consistent and
      timely data able to guide decisions and action around planning and implementation
      of maternal and newborn health programme globally. Data will be disseminated
      through a peer-reviewed manuscript, conferences and to key stakeholders within
      international organisations.

PMID- 29038183
TI  - Sociodemographic variations in the amount, duration and cost of potentially
      preventable hospitalisation for chronic conditions among Aboriginal and non
      Aboriginal Australians: a period prevalence study of linked public hospital data.
AB  - OBJECTIVES: To determine disparities in rates, length of stay (LOS) and hospital
      costs of potentially preventable hospitalisations (PPH) for selected chronic
      conditions among Aboriginal and non-Aboriginal South Australians (SA), then
      examine associations with area-level socioeconomic disadvantage and remoteness.
      SETTING: Period prevalence study using linked, administrative public hospital
      records. PARTICIPANTS: Participants included all SA residents in 2005-2006 to
      2010-2011. Analysis focused on those individuals experiencing chronic PPH as
      defined by the Australian Institute of Health and Welfare. PRIMARY OUTCOME
      MEASURES: Number and rates (unadjusted, then adjusted for sex and age) of chronic
      PPH, total LOS and direct hospital costs by Aboriginality. RESULTS: Aboriginal
      SAs experienced higher risk of index chronic PPH compared with non-Aboriginals
      (11.5 and 6.2 per 1000 persons per year, respectively) and at younger ages
      (median age 48 vs 70 years). Once hospitalised, Aboriginal people experienced
      more chronic PPH events, longer total LOS with higher costs than non-Aboriginal
      people (2.6 vs 1.9 PPH per person; 11.7 vs 9.0 days LOS; at $A17 928 vs $A11 515,
      respectively). Compared with population average LOS, the standardised rate ratio
      of LOS among Aboriginal people increased by 0.03 (95% CI 0.00 to 0.07) as
      disadvantage rank increased and 1.04 (95% CI 0.63 to 1.44) as remoteness
      increased. Non-Aboriginal LOS also increased as disadvantage increased but at a
      lower rate (0.01 (95% CI 0.01 to 0.01)). Costs of Aboriginal chronic PPH
      increased by 0.02 (95% CI 0.00 to 0.06) for each increase in disadvantage and
      1.18 (95% CI 0.80 to 1.55) for increased remoteness. Non-Aboriginal costs also
      increased as disadvantage increased but at lower rates (0.01 (95% CI 0.01 to
      0.01)). CONCLUSION: Aboriginal people's heightened risk of chronic PPH resulted
      in more time in hospital and greater cost. Systematic disparities in chronic PPH
      by Aboriginality, area disadvantage and remoteness highlight the need for
      improved uptake of effective primary care. Routine, regional reporting will help
      monitor progress in meeting these population needs.

PMID- 29038184
TI  - Optimising the quality of antibiotic prescribing in out-of-hours primary care in
      Belgium: a study protocol for an action research project.
AB  - INTRODUCTION: Antimicrobial resistance is a major public health threat driven by
      inappropriate antibiotic use, mainly in general practice and for respiratory
      tract infections. In Belgium, the quality of general practitioners' (GPs)
      antibiotic prescribing is low. To improve antibiotic use, we need a better
      understanding of this quality problem and corresponding interventions. A general
      practitioners cooperative (GPC) for out-of-hours (OOH) care presents a unique
      opportunity to reach a large group of GPs and work on quality improvement.
      Participatory action research (PAR) is a bottom-up approach that focuses on
      implementing change into daily practice and has the potential to empower
      practitioners to produce their own solutions to optimise their antibiotic
      prescribing. METHODS: This PAR study to improve antibiotic prescribing quality in
      OOH care uses a mixed methods approach. In a first exploratory phase, we will
      develop a partnership with a GPC and map the existing barriers and opportunities.
      In a second phase, we will focus on facilitating change and implementing
      interventions through PDSA (Plan-Do-Study-Act) cycles. In a third phase,
      antibiotic prescribing quality outside and antibiotic use during office hours
      will be evaluated. Equally important are the process evaluation and theory
      building on improving antibiotic prescribing. ETHICS: The study protocol was
      approved by the Ethics Committee of the Antwerp University Hospital/University of
      Antwerp. PAR unfolds in response to the needs and issues of the stakeholders,
      therefore new ethics approval will be obtained at each new stage of the research.
      DISSEMINATION: Interventions to improve antibiotic prescribing are needed now
      more than ever and outcomes will be highly relevant for GPCs, GPs in daily
      practice, national policymakers and the international scientific community. TRIAL
      REGISTRATION NUMBER: NCT03082521; Pre-results.

PMID- 29038185
TI  - Activation of professional and personal network relations when experiencing a
      symptom: a population-based cross-sectional study.
AB  - OBJECTIVE: To describe patterns of disclosure of symptoms experienced among
      people in the general population to persons in their personal and/or professional
      network. DESIGN: A population-based cross-sectional study. Data were collected
      from a web-based survey. SETTING: The general population in Denmark.
      PARTICIPANTS: 100 000 individuals randomly selected, representative of the adult
      Danish population aged >=20 years were invited. Approximately 5% were not
      eligible for inclusion. 49 706 (men=23 240; women=26 466) of 95 253 eligible
      individuals completed the questionnaire; yielding a response rate of 52.2%.
      Individuals completing all questions regarding social network relations form the
      study base (n=44 313). PRIMARY AND SECONDARY OUTCOME MEASURES: Activation of
      personal and/or professional relations when experiencing a symptom. RESULTS: The
      44 313 individuals reported in total 260 079 symptom experiences within the last
      4 weeks. No professional network relation was used in two-thirds of all reported
      symptoms. The general practitioner (GP) was the most frequently reported
      professional relation activated (22.5%). People reporting to have available
      personal relations were slightly less inclined to contact the GP (21.9%) when
      experiencing a symptom compared with people with no reported personal relations
      (26.8%). The most commonly activated personal relations were spouse/partner
      (56.4%) and friend (19.6%). More than a quarter of all reported symptom
      experiences was not shared with anyone, personal nor professional. The symptom
      experiences with the lowest frequency of network activation were symptoms such as
      black stool, constipation, change in stool texture and frequent urination.
      CONCLUSION: This study emphasises variation in the activation of network
      relations when experiencing a symptom. Symptoms were shared with both personal
      and professional relations, but different patterns of disclosures were
      discovered. For symptoms derived from the urogenital or colorectal region, the
      use of both personal and professional relations was relatively small, which might
      indicate reticence to involve other people when experiencing symptoms of that
      nature.

PMID- 29038186
TI  - Incidence, duration and cost of futile treatment in end-of-life hospital
      admissions to three Australian public-sector tertiary hospitals: a retrospective
      multicentre cohort study.
AB  - OBJECTIVES: To estimate the incidence, duration and cost of futile treatment for
      end-of-life hospital admissions. DESIGN: Retrospective multicentre cohort study
      involving a clinical audit of hospital admissions. SETTING: Three Australian
      public-sector tertiary hospitals. PARTICIPANTS: Adult patients who died while
      admitted to one of the study hospitals over a 6-month period in 2012. MAIN
      OUTCOME MEASURES: Incidences of futile treatment among end-of-life admissions;
      length of stay in both ward and intensive care settings for the duration that
      patients received futile treatments; health system costs associated with futile
      treatments; monetary valuation of bed days associated with futile treatment.
      RESULTS: The incidence rate of futile treatment in end-of-life admissions was
      12.1% across the three study hospitals (range 6.0%-19.6%). For admissions
      involving futile treatment, the mean length of stay following the onset of futile
      treatment was 15 days, with 5.25 of these days in the intensive care unit. The
      cost associated with futile bed days was estimated to be $AA12.4 million for the
      three study hospitals using health system costs, and $A988 000 when using a
      decision maker's willingness to pay for bed days. This was extrapolated to an
      annual national health system cost of $A153.1 million and a decision maker's
      willingness to pay of $A12.3 million. CONCLUSIONS: The incidence rate and cost of
      futile treatment in end-of-life admissions varied between hospitals. The overall
      impact was substantial in terms of both the bed days and cost incurred. An
      increased awareness of these economic costs may generate support for
      interventions designed to reduce futile treatments. We did not include emotional
      hardship or pain and suffering, which represent additional costs.

PMID- 29038188
TI  - Probiotics administered intravaginally as a complementary therapy combined with
      antibiotics for the treatment of bacterial vaginosis: a systematic review
      protocol.
AB  - INTRODUCTION: Bacterial vaginosis (BV) is a highly prevalent vaginal
      polymicrobial disorder commonly encountered in women of childbearing age. Therapy
      with only recommended antibiotics results in low cure rates and unacceptably high
      recurrence rates. The use of probiotics as a complementary approach for use with
      antibiotics for the treatment of BV remains unclear. This review aims to assess
      the efficacy of lactobacilli administered intravaginally in conjunction with
      antibiotics for the treatment of BV. METHODS AND ANALYSIS: The Cochrane Central
      Register of Controlled Trials in The Cochrane Library, Cochrane Library of
      Systematic Reviews, Medline/PubMed and Embase will be used to search for articles
      from database inception to November 2016. Randomised controlled clinical trials
      using lactobacilli administered intravaginally in conjunction with antibiotics to
      treat BV will be included. Primary outcome will be the BV cure rate. The
      recurrence rate will be examined as secondary outcome. Two reviewers will
      independently select trials and extract data from the original publications. The
      risk of bias will be assessed according to the Cochrane Risk of Bias tool. We
      will perform data synthesis using the Review Manager (RevMan) software V.5.2.3.
      To assess heterogeneity, we will compute the I2 statistic. ETHICS AND
      DISSEMINATION: This study will be a review of published data and it is not
      necessary to obtain ethical approval. Findings of this systematic review will be
      published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: International
      Prospective Register of Systematic Reviews 2014: CRD42014015079.

PMID- 29038189
TI  - Nodular pulmonary amyloidosis: a complex disease with malignancy association.
AB  - Pulmonary amyloidosis is a rare disease that incorporates deposition of amyloid
      microfibril material in the lung parenchyma. The condition generally presents as
      an indolent subacute-to-chronic pulmonary disease and requires tissue biopsy to
      establish the diagnosis. Nodular pulmonary amyloidosis, a subtype of pulmonary
      amyloidosis, is characterised by special radiographic and pathological features.
      While the disease can be associated with inflammatory conditions; its association
      with mucosal-associated lymphoid tissue (MALT lymphoma) is unusual and carries
      management challenges. Herein, we illustrate a case study of nodular pulmonary
      amyloidosis associated with underlying MALT lymphoma in a patient with known
      systemic lupus erythematosus. The aim of this article is to share the management
      experience of this complex condition with the medical community and to conduct an
      up-to-date literature review on nodular pulmonary amyloidosis.

PMID- 29038187
TI  - Health-related quality of life variations by sociodemographic factors and chronic
      conditions in three metropolitan cities of South Asia: the CARRS study.
AB  - OBJECTIVES: Health-related quality of life (HRQOL) is a key indicator of health.
      However, HRQOL data from representative populations in South Asia are lacking.
      This study aims to describe HRQOL overall, by age, gender and socioeconomic
      status, and examine the associations between selected chronic conditions and
      HRQOL in adults from three urban cities in South Asia. METHODS: We used data from
      16 287 adults aged >=20 years from the baseline survey of the Centre for
      Cardiometabolic Risk Reduction in South Asia cohort (2010-2011). HRQOL was
      measured using the European Quality of Life Five Dimension-Visual Analogue Scale
      (EQ5D-VAS), which measures health status on a scale of 0 (worst health status) to
      100 (best possible health status). RESULTS: 16 284 participants completed the
      EQ5D-VAS. Mean age was 42.4 (+/-13.3) years and 52.4% were women. 14% of the
      respondents reported problems in mobility and pain/discomfort domains. Mean VAS
      score was 74 (95% CI 73.7 to 74.2). Significantly lower health status was found
      in elderly (64.1), women (71.6), unemployed (68.4), less educated (71.2) and low
      income group (73.4). Individuals with chronic conditions reported worse health
      status than those without (67.4 vs 76.2): prevalence ratio, 1.8 (95% CI 1.61 to
      2.04). CONCLUSIONS: Our data demonstrate significantly lower HRQOL in key
      demographic groups and those with chronic conditions, which is consistent with
      previous studies. These data provide insights on inequalities in population
      health status, and potentially reveal unmet needs in the community to guide
      health policies.

PMID- 29038191
TI  - Obstructive uropathy as initial presentation of genitourinary tuberculosis and
      masquerading as a postsurgical complication.
AB  - A 46-year-old woman who had a recent total abdominal hysterectomy presented with
      a 1 month history of lower abdominal pain, 1 week of nausea and vomiting as well
      as decreased urinary output preceded by a year of significant unintentional
      weight loss. On renal imaging, she was found to have bilateral hydronephrosis and
      hydroureters in the setting of bilateral distal ureteric obstruction complicated
      with acute kidney injury and severe hyperkalaemia requiring haemodialysis. The
      initial concern was for ureteric injury, a known complication of abdominal
      hysterectomy procedures, however, a urological intervention, performed 9 months
      later to relieve the ureteric obstruction, revealed purulent material within the
      left ureter that was smear positive for acid fast bacilli. A GeneXpert test was
      positive for Mycobacterium tuberculosis She was diagnosed with genitourinary
      tuberculosis and responded well to antitubercular treatment and haemodialysis was
      discontinued after the surgery relieved her ureteric obstruction.

PMID- 29038190
TI  - Effect of autologous adipose-derived mesenchymal stem cell therapy in the
      treatment of a post-traumatic chondral defect of the knee.
AB  - Isolated chondral defects have a limited capacity to heal and predispose to the
      development of osteoarthritis. Current surgical management can be unpredictable
      in outcome. Improved understanding of the action of mesenchymal stem cells (MSCs)
      has seen renewed interest in their role in cartilage repair. A 26-year-old
      athlete presented with a post-traumatic, isolated patella chondral defect. The
      patient underwent an arthroscopy with removal of a chondral loose body. After
      failure to symptomatically improve 12 months following surgery, the patient
      received intra-articular autologous adipose-derived mesenchymal stem cell (ADMSC)
      therapy.

PMID- 29038192
TI  - Two gaps too many, three clues too few? Do elevated osmolal and anion gaps with
      crystalluria always mean ethylene glycol poisoning?
AB  - A 60-year-old African-American man with a medical history significant for heavy
      alcohol abuse, hypertension, delirium tremens, nephrolithiasis and seizure
      disorder was brought to the hospital with altered mental status. He was found to
      have high anion gap metabolic acidosis with significantly elevated lactate along
      with an elevated osmolal gap and calcium oxalate crystals in his urine. With this
      combination of findings, ethylene glycol poisoning was high in the differential.
      This case report describes why ethylene glycol poisoning was not the diagnosis in
      this patient despite the presence of these three classic laboratory findings,
      therefore emphasising the fact that these findings should not be taken at face
      value because they can be seen collectively in a patient yet each have a
      different cause.

PMID- 29038193
TI  - Recurrent episodes of esophageal candidiasis without dysphagia post-Guillain
      Barre syndrome: an unusual presentation of achalasia.
AB  - Here, we present a case of a 50-year-old male with a history of a Guillain-Barre
      syndrome, who was referred to our clinic with recurrent esophageal candidiasis
      and long-standing intermittent retrosternal cramps for further evaluation. Other
      symptoms such as dysphagia, regurgitations and weight loss were denied, and prior
      repeated endoscopy was otherwise unremarkable. Using high resolution impedance
      manometry, we could demonstrate a panesophageal pressure increase on water
      swallows and complete aperistalsis of the tubular esophagus, indicating achalasia
      type II. However, due to the patient's extraordinary body height and resulting
      length of the esophagus, endoluminal functional lumen imaging probe analysis
      supplementary to high resolution impedance manometry needed to be used to assess
      distensibility of the esophagogastral junction and to secure the diagnosis of
      achalasia before appropriately treating the patient with pneumatic dilation.

PMID- 29038194
TI  - Rare case of disseminated rhinosporidiosis with chronic osteomyelitis of the
      calcaneum treated by a simple technique of negative pressure wound therapy.
AB  - Occurrence of nasal, cutaneous and disseminated rhinosporidiosis in the same
      patient is uncommon and involvement of calcaneum is rare. Rhinosporidial
      osteomyelitis is treated surgically, but multiple recurrences and local spread
      are common. Many a times, surgical ablation or amputation of the involved area of
      the limb is carried out to prevent recurrences. We present a case of
      rhinosporidial osteomyelitis of the calcaneum with a chronic discharging sinus
      and large lytic lesion in the calcaneum treated by an alternative surgical option
      in the form of debridement and negative pressure wound therapy.

PMID- 29038195
TI  - Discoid lupus erythematosus: when a superficial injury is a red herring of
      underlying disease.

PMID- 29038196
TI  - Caecal volvulus with intestinal malrotation: need for caecopexy?

PMID- 29038197
TI  - Obstructive coronary artery disease in patient with acute thrombotic
      thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) affects essentially all organ systems.
      Myocardial injury in TTP is often attributed to microthrombi formation. We
      present the first case report in the literature of an acute TTP patient with
      concomitant obstructive coronary artery disease (CAD) and acute myocardial
      infarction who underwent successful percutaneous coronary intervention (PCI). A
      70-year-old female patient who was diagnosed with acute TTP required plasma
      exchange. The patient also experienced episodes of angina pectoris, elevated
      cardiac enzymes and global ST segment depressions on ECG. A subsequent non
      invasive ischaemia workup revealed significant ischaemia. Coronary angiography
      revealed obstructive CAD in her right coronary artery, requiring PCI with a bare
      metal stent placement and dual antiplatelet therapy. The patient tolerated
      antiplatelet therapy well. At 6 months of follow-up, she had no recurrent angina.
      This case highlights the potential co-existence of obstructive CAD and acute TTP
      requiring careful differential diagnosis and treatment.

PMID- 29038198
TI  - Dysphagia due to DISH-related anterior osteophytes: DISHphagia!!

PMID- 29038199
TI  - Does the Treatment of Obstructive Sleep Apnea and Obesity Improve Pulsatile
      Hemodynamics?

PMID- 29038200
TI  - Renal Denervation After the SPYRAL HTN-OFF MED Trial: Putting a Complex Study
      Into Context.

PMID- 29038201
TI  - Kinin B1 Receptor Promotes Neurogenic Hypertension Through Activation of
      Centrally Mediated Mechanisms.
AB  - Hypertension is associated with increased activity of the kallikrein-kinin
      system. Kinin B1 receptor (B1R) activation leads to vasoconstriction and
      inflammation. Despite evidence supporting a role for the B1R in blood pressure
      regulation, the mechanisms by which B1R could alter autonomic function and
      participate in the pathogenesis of hypertension remain unidentified. We sought to
      explore whether B1R-mediated inflammation contributes to hypertension and
      investigate the molecular mechanisms involved. In this study, we tested the
      hypothesis that activation of B1R in the brain is involved in the pathogenesis of
      hypertension, using the deoxycorticosterone acetate-salt model of neurogenic
      hypertension in wild-type and B1R knockout mice. Deoxycorticosterone acetate-salt
      treatment in wild-type mice led to significant increases in B1R mRNA and protein
      levels and bradykinin levels, enhanced gene expression of carboxypeptidase N
      supporting an increase in the B1R ligand, associated with enhanced blood
      pressure, inflammation, sympathoexcitation, autonomic dysfunction, and impaired
      baroreflex sensitivity, whereas these changes were blunted or prevented in B1R
      knockout mice. B1R stimulation was further shown to involve activation of the
      ASK1-JNK-ERK1/2 and NF-kappaB pathways in the brain. To dismiss potential
      developmental alterations in knockout mice, we further used B1R blockade
      selectively in the brain of wild-type mice. Supporting the central origin of this
      mechanism, intracerebroventricular infusion of a specific B1R antagonist,
      attenuated the deoxycorticosterone acetate-salt-induced increase in blood
      pressure in wild-type mice. Our data provide the first evidence of a central role
      for B1R-mediated inflammatory pathways in the pathogenesis of deoxycorticosterone
      acetate-salt hypertension and offer novel insights into possible B1R-targeted
      therapies for the treatment of neurogenic hypertension.

PMID- 29038202
TI  - Brain Regional Blood Flow and Working Memory Performance Predict Change in Blood
      Pressure Over 2 Years.
AB  - Hypertension is a presumptive risk factor for premature cognitive decline.
      However, lowering blood pressure (BP) does not uniformly reverse cognitive
      decline, suggesting that high BP per se may not cause cognitive decline. We
      hypothesized that essential hypertension has initial effects on the brain that,
      over time, manifest as cognitive dysfunction in conjunction with both brain
      vascular abnormalities and systemic BP elevation. Accordingly, we tested whether
      neuropsychological function and brain blood flow responses to cognitive
      challenges among prehypertensive individuals would predict subsequent progression
      of BP. Midlife adults (n=154; mean age, 49; 45% men) with prehypertensive BP
      underwent neuropsychological testing and assessment of regional cerebral blood
      flow (rCBF) response to cognitive challenges. Neuropsychological performance
      measures were derived for verbal and logical memory (memory), executive function,
      working memory, mental efficiency, and attention. A pseudo-continuous arterial
      spin labeling magnetic resonance imaging sequence compared rCBF responses with
      control and active phases of cognitive challenges. Brain areas previously
      associated with BP were grouped into composites for frontoparietal,
      frontostriatal, and insular-subcortical rCBF areas. Multiple regression models
      tested whether BP after 2 years was predicted by initial BP, initial
      neuropsychological scores, and initial rCBF responses to cognitive challenge. The
      neuropsychological composite of working memory (standardized beta, -0.276;
      se=0.116; P=0.02) and the frontostriatal rCBF response to cognitive challenge
      (standardized beta, 0.234; se=0.108; P=0.03) significantly predicted follow-up
      BP. Initial BP failed to significantly predict subsequent cognitive performance
      or rCBF. Changes in brain function may precede or co-occur with progression of BP
      toward hypertensive levels in midlife.

PMID- 29038205
TI  - The Ethics of Conducting Clinical Trials With Sodium-Glucose Cotransporter-2
      Inhibitors in Heart Failure: Is Placebo Assignment Justified in Patients With
      Comorbid Diabetes Mellitus and Heart Failure?

PMID- 29038203
TI  - Effect of CPAP, Weight Loss, or CPAP Plus Weight Loss on Central Hemodynamics and
      Arterial Stiffness.
AB  - : Obesity and obstructive sleep apnea tend to coexist. Little is known about the
      effects of obstructive sleep apnea, obesity, or their treatment on central aortic
      pressures and large artery stiffness. We randomized 139 adults with obesity (body
      mass index >30 kg/m2) and moderate-to-severe obstructive sleep apnea to (1)
      continuous positive airway pressure (CPAP) therapy (n=45), (2) weight loss (WL)
      therapy (n=48), or (3) combined CPAP and WL (n=46) for 24 weeks. We assessed the
      effect of these interventions on central pressures and carotid-femoral pulse wave
      velocity (a measure of large artery stiffness), measured with arterial tonometry.
      Central systolic pressure was reduced significantly only in the combination arm (
      7.4 mm Hg; 95% confidence interval, -12.5 to -2.4 mm Hg; P=0.004), without
      significant reductions detected in either the WL-only (-2.3 mm Hg; 95% confidence
      interval, -7.5 to 3.0; P=0.39) or the CPAP-only (-3.1 mm Hg; 95% confidence
      interval, -8.3 to 2.0; P=0.23) arms. However, none of these interventions
      significantly changed central pulse pressure, pulse pressure amplification, or
      the central augmentation index. The change in mean arterial pressure (P=0.008)
      and heart rate (P=0.027) induced by the interventions was significant predictors
      of the change in carotid-femoral pulse wave velocity. However, after adjustment
      for mean arterial pressure and heart rate, no significant changes in carotid
      femoral pulse wave velocity were observed in any group. In obese subjects with
      obstructive sleep apnea, combination therapy with WL and CPAP is effective in
      reducing central systolic pressure. However, this effect is largely mediated by
      changes in mean, rather than central pulse pressure. WL and CPAP, alone or in
      combination, did not reduce large artery stiffness in this population. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00371293.

PMID- 29038206
TI  - Closing the Genotype-Phenotype Loop for Precision Medicine.

PMID- 29038204
TI  - Do We Need a Patient-Centered Target for Systolic Blood Pressure in Hypertensive
      Patients With Type 2 Diabetes Mellitus?
AB  - The current trend on diabetes mellitus management advocates replacing the
      paradigm from a uniform to an individualized patient-centered systolic blood
      pressure (SBP), but there is no consensus on the achieved treatment goals of SBP
      level. The study aimed at evaluating the association between SBP and the risk of
      cardiovascular diseases (CVD) and all-cause mortality for diabetic patients to
      identify patient-centered treatment targets. A retrospective study was conducted
      on 95 086 Chinese adult primary care patients with type 2 diabetes mellitus and
      hypertension. Using the average of the annual SBP records (updated SBP) over a
      median follow-up of 5.9 years, the risks of overall CVD, all-cause mortality, and
      their composite associated with SBP were evaluated using Cox proportional hazards
      regression. Subgroup analysis was performed on the incidence of CVD by
      stratifying patient's baseline characteristics. The SBP range for the lowest risk
      of CVD and all-cause mortality was 130 to 134 mm Hg among type 2 diabetes
      mellitus population. A J-shaped curvilinear relationship was identified between
      SBP and risk of CVD and all-cause mortality, irrespective of patients'
      characteristics. The findings showed that all patients with SBP <125 mm Hg or
      >=140 mm Hg had an increased risk of CVD and mortality. This large territory-wide
      study showed the level of achieved SBP of 125 to 139 mm Hg in pharmacological
      therapy, irrespective of patients' characteristics, suggested that the SBP
      treatment goal of <140 mm Hg and individualized SBP target may not be necessary
      in diabetic management.

PMID- 29038207
TI  - FunSel: Mesenchymal Stromal Cells Stay for the Party.

PMID- 29038208
TI  - DNA Methylation and Human Heart Failure: Mechanisms or Prognostics.

PMID- 29038209
TI  - Activation and Inhibition of Sodium-Hydrogen Exchanger Is a Mechanism That Links
      the Pathophysiology and Treatment of Diabetes Mellitus With That of Heart
      Failure.
AB  - The mechanisms underlying the progression of diabetes mellitus and heart failure
      are closely intertwined, such that worsening of one condition is frequently
      accompanied by worsening of the other; the degree of clinical acceleration is
      marked when the 2 coexist. Activation of the sodium-hydrogen exchanger in the
      heart and vasculature (NHE1 isoform) and the kidneys (NHE3 isoform) may serve as
      a common mechanism that links both disorders and may underlie their interplay.
      Insulin insensitivity and adipokine abnormalities (the hallmarks of type 2
      diabetes mellitus) are characteristic features of heart failure; conversely,
      neurohormonal systems activated in heart failure (norepinephrine, angiotensin II,
      aldosterone, and neprilysin) impair insulin sensitivity and contribute to
      microvascular disease in diabetes mellitus. Each of these neurohormonal
      derangements may act through increased activity of both NHE1 and NHE3. Drugs used
      to treat diabetes mellitus may favorably affect the pathophysiological mechanisms
      of heart failure by inhibiting either or both NHE isoforms, and drugs used to
      treat heart failure may have beneficial effects on glucose tolerance and the
      complications of diabetes mellitus by interfering with the actions of NHE1 and
      NHE3. The efficacy of NHE inhibitors on the risk of cardiovascular events may be
      enhanced when heart failure and glucose intolerance coexist and may be attenuated
      when drugs with NHE inhibitory actions are given concomitantly. Therefore, the
      sodium-hydrogen exchanger may play a central role in the interplay of diabetes
      mellitus and heart failure, contribute to the physiological and clinical
      progression of both diseases, and explain certain drug-drug and drug-disease
      interactions that have been reported in large-scale randomized clinical trials.

PMID- 29038210
TI  - Increases in Natriuretic Peptides Precede Heart Failure Hospitalization in
      Patients With a Recent Coronary Event and Type 2 Diabetes Mellitus.

PMID- 29038211
TI  - Letter by Musso et al Regarding Article, "Cardiac Outcomes After Ischemic Stroke
      or Transient Ischemic Attack: Effects of Pioglitazone in Patients With Insulin
      Resistance Without Diabetes Mellitus".

PMID- 29038212
TI  - Letter by Jin-Shan and Xue-Bin Regarding Article, "Cardiac Outcomes After
      Ischemic Stroke or Transient Ischemic Attack: Effects of Pioglitazone in Patients
      With Insulin Resistance Without Diabetes Mellitus".

PMID- 29038213
TI  - Response by Young et al to Letters Regarding Article, "Cardiac Outcomes After
      Ischemic Stroke or Transient Ischemic Attack: Effects of Pioglitazone in Patients
      With Insulin Resistance Without Diabetes Mellitus".

PMID- 29038215
TI  - Correction to: 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of
      Patients With Syncope: A Report of the American College of Cardiology/American
      Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm
      Society.

PMID- 29038214
TI  - Correction to 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of
      Patients With Syncope: Executive Summary: A Report of the American College of
      Cardiology/American Heart Association Task Force on Clinical Practice Guidelines
      and the Heart Rhythm Society.

PMID- 29038216
TI  - Is abdominal hypopressive technique effective in the prevention and treatment of
      pelvic floor dysfunction? Marketing or evidence from high-quality clinical
      trials?

PMID- 29038217
TI  - Hippocampal area CA1 and remote memory in rats.
AB  - Hippocampal lesions often produce temporally graded retrograde amnesia (TGRA),
      whereby recent memory is impaired more than remote memory. This finding has
      provided support for the process of systems consolidation. However, temporally
      graded memory impairment has not been observed with the watermaze task, and the
      findings have been inconsistent with context fear conditioning. One possibility
      is that large hippocampal lesions indirectly disrupt (by retrograde degeneration)
      the function of areas that project to the hippocampus that are important for task
      performance or thought to be important for storing consolidated memories. We
      developed a discrete lesion targeting area CA1, the sole output of the
      hippocampus to neocortex, and tested the effects of this lesion on recent and
      remote memory in the watermaze task, in context fear conditioning, and in trace
      fear conditioning. In all three tasks, recent and remote memory were similarly
      impaired after CA1 lesions. We discuss factors that help to illuminate these
      findings and consider their relevance to systems consolidation.

PMID- 29038218
TI  - Experiential learning in rodents: past experience enables rapid learning and
      localized encoding in hippocampus.
AB  - Humans routinely use past experience with complexity to deal with novel,
      challenging circumstances. This fundamental aspect of real-world behavior has
      received surprisingly little attention in animal studies, and the underlying
      brain mechanisms are unknown. The present experiments tested for transfer from
      past experience in rats and then used quantitative imaging to localize synaptic
      modifications in hippocampus. Six daily exposures to an enriched environment (EE)
      caused a marked enhancement of short- and long-term memory encoded during a 30
      min session in a different and complex environment relative to rats given
      extensive handling or access to running wheels. Relatedly, the EE animals
      investigated the novel environment in a different manner than the other groups,
      suggesting transfer of exploration strategies acquired in earlier interactions
      with complexity. This effect was not associated with changes in the number or
      size of excitatory synapses in hippocampus. Maps of synapses expressing a marker
      for long-term potentiation indicated that encoding in the EE group, relative to
      control animals, was concentrated in hippocampal field CA1. Importantly, <1% of
      the total population of synapses was involved in production of the regional map.
      These results constitute the first evidence that the transfer of experience
      profoundly affects the manner in which hippocampus encodes complex information.

PMID- 29038219
TI  - The L-type voltage-gated calcium channel CaV1.2 mediates fear extinction and
      modulates synaptic tone in the lateral amygdala.
AB  - L-type voltage-gated calcium channels (LVGCCs) have been implicated in both the
      formation and the reduction of fear through Pavlovian fear conditioning and
      extinction. Despite the implication of LVGCCs in fear learning and extinction,
      studies of the individual LVGCC subtypes, CaV1.2 and CaV1.3, using transgenic
      mice have failed to find a role of either subtype in fear extinction. This
      discontinuity between the pharmacological studies of LVGCCs and the studies
      investigating individual subtype contributions could be due to the limited
      neuronal deletion pattern of the CaV1.2 conditional knockout mice previously
      studied to excitatory neurons in the forebrain. To investigate the effects of
      deletion of CaV1.2 in all neuronal populations, we generated CaV1.2 conditional
      knockout mice using the synapsin1 promoter to drive Cre recombinase expression.
      Pan-neuronal deletion of CaV1.2 did not alter basal anxiety or fear learning.
      However, pan-neuronal deletion of CaV1.2 resulted in a significant deficit in
      extinction of contextual fear, implicating LVGCCs, specifically CaV1.2, in
      extinction learning. Further exploration on the effects of deletion of CaV1.2 on
      inhibitory and excitatory input onto the principle neurons of the lateral
      amygdala revealed a significant shift in inhibitory/excitatory balance. Together
      these data illustrate an important role of CaV1.2 in fear extinction and the
      synaptic regulation of activity within the amygdala.

PMID- 29038220
TI  - Context memory formation requires activity-dependent protein degradation in the
      hippocampus.
AB  - Numerous studies have indicated that the consolidation of contextual fear
      memories supported by an aversive outcome like footshock requires de novo protein
      synthesis as well as protein degradation mediated by the ubiquitin-proteasome
      system (UPS). Context memory formed in the absence of an aversive stimulus by
      simple exposure to a novel environment requires de novo protein synthesis in both
      the dorsal (dHPC) and ventral (vHPC) hippocampus. However, the role of UPS
      mediated protein degradation in the consolidation of context memory in the
      absence of a strong aversive stimulus has not been investigated. In the present
      study, we used the context preexposure facilitation effect (CPFE) procedure,
      which allows for the dissociation of context learning from context-shock
      learning, to investigate the role of activity-dependent protein degradation in
      the dHPC and vHPC during the formation of a context memory. We report that
      blocking protein degradation with the proteasome inhibitor clasto-lactacystin
      beta-lactone (betaLac) or blocking protein synthesis with anisomycin (ANI)
      immediately after context preexposure significantly impaired context memory
      formation. Additionally, we examined 20S proteasome activity at different time
      points following context exposure and saw that the activity of proteasomes in the
      dHPC increases immediately after stimulus exposure while the vHPC exhibits a
      biphasic pattern of proteolytic activity. Taken together, these data suggest that
      the requirement of increased proteolysis during memory consolidation is not
      driven by processes triggered by the strong aversive outcome (i.e., shock)
      normally used to support fear conditioning.

PMID- 29038221
TI  - Prazosin during threat discrimination boosts memory of the safe stimulus.
AB  - The alpha-1 adrenoreceptor antagonist prazosin has shown promise in the treatment
      of post-traumatic stress disorder (PTSD) symptoms, but its mechanisms are not
      well understood. Here we administered prazosin or placebo prior to threat
      conditioning (day 1) and tested subsequent extinction (day 2) and reextinction
      (day 3) in healthy human participants. Prazosin did not affect threat
      conditioning but augmented stimulus discrimination during extinction and
      reextinction, via lower responding to the safe stimulus. These results suggest
      that prazosin during threat acquisition may have influenced encoding or
      consolidation of safety processing in particular, subsequently leading to
      enhanced discrimination between the safe and threatening stimuli.

PMID- 29038222
TI  - Post-training reversible disconnection of the ventral hippocampal-basolateral
      amygdaloid circuits impairs consolidation of inhibitory avoidance memory in rats.
AB  - The ventral hippocampus (VH) and the basolateral amygdala (BLA) are both crucial
      in inhibitory avoidance (IA) memory. However, the exact role of the VH-BLA
      circuit in IA memory consolidation is unclear. This study investigated the effect
      of post-training reversible disconnection of the VH-BLA circuit in IA memory
      consolidation. Male Wistar rats with implanted guide cannulae were trained with a
      one-trial IA task, then received immediate intracerebral injections of muscimol
      or saline, and were tested 24 h later. Muscimol injection into the bilateral BLA,
      or the unilateral VH and contralateral BLA, but not the unilateral VH and
      ipsilateral BLA, significantly decreased the retention latencies (versus saline
      treatment). The results suggest that the VH-BLA circuit could be an important
      circuit to modulate consolidation of IA memory in rats.

PMID- 29038224
TI  - Effect of Elective Percutaneous Coronary Intervention on Hyperemic Absolute
      Coronary Blood Flow Volume and Microvascular Resistance.
AB  - BACKGROUND: The hemodynamics involved in the relationship between absolute
      coronary blood flow (ABF) volume and myocardial resistance (MR) are complex, and
      the effect of percutaneous coronary intervention (PCI) on their changes remains
      unclear. The aim of this study was to investigate the differences in hyperemic
      ABF and MR before and after elective PCI using a thermodilution method. METHODS
      AND RESULTS: We investigated 28 vessels (right coronary artery, 9; left anterior
      descending coronary artery, 18; left circumflex coronary artery, 1) from 28
      patients with stable angina pectoris undergoing elective PCI. ABF was measured
      pre- and post-PCI using a pressure-temperature sensor-equipped wire, based on a
      thermodilution method with a continuous saline infusion of 20 mL/min through a
      proximally located microcatheter with an end-hole in the target vessel. MR equals
      distal coronary perfusion pressure divided by ABF at maximal hyperemia.
      Conventional fractional flow reserve was also measured pre- and post-PCI.
      Fractional flow reserve increased significantly after PCI (from 0.70 [0.65-0.75]
      to 0.88 [0.85-0.95]) in all examined territories. ABF also increased
      significantly (from 137.8 mL/min [86.3-180.8 mL/min] to 173.3 mL/min [137.9-234.3
      mL/min] ; increase: 52.8 mL/min [9.7-80.8 mL/min]) while MR decreased in 11
      vessels and increased in 17. No significant relationship was detected between
      these increases in fractional flow reserve and ABF. Both pre- and post-PCI MR
      distributed in a wide range, and there was a significant relationship between pre
      PCI MR and the increase in ABF (r=0.44; P=0.02) although no significant change in
      MR was observed between pre- and post-PCI (P=0.37). CONCLUSIONS: Direct
      measurement of ABF and MR using thermodilution method offers a feasible approach
      that could shed a light on previously unclear aspects of coronary hemodynamics.

PMID- 29038225
TI  - Role of Proximal Optimization Technique Guided by Intravascular Ultrasound on
      Stent Expansion, Stent Symmetry Index, and Side-Branch Hemodynamics in Patients
      With Coronary Bifurcation Lesions.
AB  - BACKGROUND: Bench models of coronary bifurcation lesions demonstrated that the
      proximal optimization technique (POT) expanded the stent and opened the side
      branch (SB). We investigated the role of POT guided by intravascular ultrasound
      on the main vessel (MV) stent expansion and SB fractional flow reserve (FFR) in
      patients with coronary bifurcation lesion. METHODS AND RESULTS: In 40 patients
      with coronary bifurcation lesion, 120 intravascular ultrasound examinations of
      the MV were performed at baseline, after MV stenting, and POT followed by 95 FFR
      measurements of the SB. In the proximal stent segment, stent volume index and
      minimum stent area were larger after POT versus MV stenting (9.2+/-3.4 versus
      7.40+/-2.0 mm3/mm and 7.65+/-1.8 versus 6.38+/-1.7 mm2, respectively; P<0.01). In
      the bifurcation segment, minimum stent area was larger after POT versus MV
      stenting (6.45+/-2.1 versus 5.9+/-2.0 mm2, respectively; P<0.05). POT expanded
      the stent symmetrically. After POT, SB FFR was <0.75 in 12 patients (30%), which
      improved to >0.75 after SB dilation or SB stenting+final POT. SB FFR was
      significantly higher after POT+SB dilation or SB stenting+final POT versus after
      MV stenting and POT. CONCLUSIONS: This is the first study of POT guided by
      intravascular ultrasound in patients with coronary bifurcation lesion,
      demonstrating that POT symmetrically expanded the proximal and bifurcation
      segments of the stent. After POT, SB FFR was <0.75 in a third of patients, which
      improved to >0.75 after SB dilation or SB stenting+final POT.

PMID- 29038223
TI  - Modulation of target recollection and recollection rejection networks due to
      retrieval facilitation and interference.
AB  - To better understand neural recollection processing, we induced interference in
      target recollection by presenting related lures before their respective targets
      and facilitated recollection rejection of lures by presenting targets before
      their related lures. Target recollection following interference recruited visual
      and prefrontal cortices, showing that these regions support recollection when
      related information has disrupted target representations. Recollection rejection
      following target presentation recruited angular gyrus, indicating that this
      region supports recollection rejection when target representations are strong and
      highly accessible. Thus, recollection networks are sensitive to the accessibility
      of target representations that are affected by the presentation of related
      information during retrieval.

PMID- 29038226
TI  - Letter by Uretsky et al Regarding Article, "Prognostic Value of Fractional Flow
      Reserve Measured Immediately After Drug-Eluting Stent Implantation".

PMID- 29038227
TI  - Quantification of Absolute Coronary Blood Flow and Microvascular Resistance.

PMID- 29038228
TI  - Response by Piroth et al to Letter Regarding Article, "Prognostic Value of
      Fractional Flow Reserve Measured Immediately After Drug-Eluting Stent
      Implantation".

PMID- 29038230
TI  - Constitutive activity of the Ghrelin receptor reduces surface expression of
      voltage-gated Ca2+ channels in a CaVbeta-dependent manner.
AB  - Voltage-gated Ca2+ (CaV) channels couple membrane depolarization to Ca2+ influx,
      triggering a range of Ca2+-dependent cellular processes. CaV channels are,
      therefore, crucial in shaping neuronal activity and function, depending on their
      individual temporal and spatial properties. Furthermore, many neurotransmitters
      and drugs that act through G protein coupled receptors (GPCRs), modulate neuronal
      activity by altering the expression, trafficking, or function of CaV channels.
      GPCR-dependent mechanisms that downregulate CaV channel expression levels are
      observed in many neurons but are, by comparison, less studied. Here we show that
      the growth hormone secretagogue receptor type 1a (GHSR), a GPCR, can inhibit the
      forwarding trafficking of several CaV subtypes, even in the absence of agonist.
      This constitutive form of GPCR inhibition of CaV channels depends on the presence
      of a CaVbeta subunit. CaVbeta subunits displace CaValpha1 subunits from the
      endoplasmic reticulum. The actions of GHSR on CaV channels trafficking suggest a
      role for this signaling pathway in brain areas that control food intake, reward,
      and learning and memory.

PMID- 29038229
TI  - The polymorphic proteins TgrB1 and TgrC1 function as a ligand-receptor pair in
      Dictyostelium allorecognition.
AB  - Allorecognition is a key factor in Dictyostelium development and sociality. It is
      mediated by two polymorphic transmembrane proteins, TgrB1 and TgrC1, which
      contain extracellular immunoglobulin domains. TgrB1 and TgrC1 are necessary and
      sufficient for allorecognition, and they carry out separate albeit overlapping
      functions in development, but their mechanism of action is unknown. Here, we show
      that TgrB1 acts as a receptor with TgrC1 as its ligand in cooperative aggregation
      and differentiation. The proteins bind each other in a sequence-specific manner;
      TgrB1 exhibits a cell-autonomous function and TgrC1 acts non-cell-autonomously.
      The TgrB1 cytoplasmic tail is essential for its function and it becomes
      phosphorylated upon association with TgrC1. Dominant mutations in TgrB1 activate
      the receptor function and confer partial ligand independence. These roles in
      development and sociality suggest that allorecognition is crucial in the
      integration of individual cells into a coherent organism.

PMID- 29038231
TI  - Evaluation of Clinical Drug Interaction Potential of Clofazimine Using Static and
      Dynamic Modeling Approaches.
AB  - The 2016 World Health Organization treatment recommendations for drug-resistant
      tuberculosis (DR-TB) positioned clofazimine as a core second-line drug. Being
      identified as a cytochrome P450 (P450) inhibitor in vitro, a P450-mediated drug
      interaction may be likely when clofazimine is coadministered with substrates of
      these enzymes. The P450-mediated drug interaction potential of clofazimine was
      evaluated using both static [estimation of the R1 and area under the plasma
      concentration-time curve ratio (AUCR) values] and dynamic [physiologically based
      pharmacokinetics (PBPK)] modeling approaches. For static and dynamic predictions,
      midazolam, repaglinide, and desipramine were used as probe substrates for
      CYP3A4/5, CYP2C8, and CYP2D6, respectively. The AUCR static model estimations for
      clofazimine with the substrates midazolam, repaglinide, and desipramine were
      5.59, 1.34, and 1.69, respectively. The fold increases in the area under the
      curve (AUC) predicted for midazolam, repaglinide, and desipramine with
      clofazimine (based on PBPK modeling) were 2.69, 1.60, and 1.47, respectively.
      Clofazimine was predicted to be a moderate-to-strong CYP3A4/5 inhibitor and weak
      CYP2C8 and CYP2D6 inhibitor based on the calculated AUCR by static and PBPK
      modeling. Additionally, for selected antiretroviral, antitubercular,
      antihypertensive, antidiabetic, antileprotics, and antihyperlipidemic CYP3A4/5
      substrate drugs, approximately 2- to 6-fold increases in the AUC were predicted
      with static modeling when coadministered with 100 mg of clofazimine. Therefore,
      the possibility of an increase in the AUC of CYP3A4/5 substrates when
      coadministered with clofazimine cannot be ignored.

PMID- 29038233
TI  - Development of Molecularly Driven Targeted Combination Strategies.

PMID- 29038232
TI  - Tissue Force Programs Cell Fate and Tumor Aggression.
AB  - Biomechanical and biochemical cues within a tissue collaborate across length
      scales to direct cell fate during development and are critical for the
      maintenance of tissue homeostasis. Loss of tensional homeostasis in a tissue not
      only accompanies malignancy but may also contribute to oncogenic transformation.
      High mechanical stress in solid tumors can impede drug delivery and may
      additionally drive tumor progression and promote metastasis. Mechanistically,
      biomechanical forces can drive tumor aggression by inducing a mesenchymal-like
      switch in transformed cells so that they attain tumor-initiating or stem-like
      cell properties. Given that cancer stem cells have been linked to metastasis and
      treatment resistance, this raises the intriguing possibility that the elevated
      tissue mechanics in tumors could promote their aggression by programming their
      phenotype toward that exhibited by a stem-like cell.Significance: Recent findings
      argue that mechanical stress and elevated mechanosignaling foster malignant
      transformation and metastasis. Prolonged corruption of tissue tension may drive
      tumor aggression by altering cell fate specification. Thus, strategies that could
      reduce tumor mechanics might comprise effective approaches to prevent the
      emergence of treatment-resilient metastatic cancers. Cancer Discov; 7(11); 1224
      37. (c)2017 AACR.

PMID- 29038234
TI  - Patient-Reported Symptom Control of Diarrhea and Flushing in Patients with
      Neuroendocrine Tumors Treated with Lanreotide Depot/Autogel: Results from a
      Randomized, Placebo-Controlled, Double-Blind and 32-Week Open-Label Study.
AB  - BACKGROUND: In the double-blind (DB) ELECT study, lanreotide depot/autogel
      significantly reduced versus placebo the need for short-acting octreotide for
      symptomatic carcinoid syndrome (CS) control in neuroendocrine tumor (NET)
      patients. Here we present patient-reported symptom data during DB and initial
      open-label (IOL) treatment. MATERIALS AND METHODS: Adults with NETs and CS
      history, with/without prior somatostatin analog use, were randomized to 16 weeks'
      DB lanreotide 120 mg subcutaneous or placebo every 4 weeks, followed by 32 weeks'
      IOL lanreotide. Patients recorded diarrhea and/or flushing frequency and severity
      daily by Interactive Voice (Web) Response System for 1 month prior to
      randomization and throughout the study. RESULTS: Of 115 patients randomized (n =
      59 lanreotide, n = 56 placebo), 56 lanreotide and 45 placebo patients enrolled in
      the IOL phase. During DB treatment, least square (LS) mean percentages of days
      with moderate/severe diarrhea and/or flushing were significantly lower for
      lanreotide (23.4%) versus placebo (35.8%; LS mean difference [95% confidence
      interval]: -12.4 [-20.73 to -4.07]; p = .004). For DB lanreotide patients,
      average daily composite (frequency * severity) diarrhea scores improved
      significantly between DB and IOL treatment (mean difference: -0.71 [-1.20 to 
      0.22]; p = .005), and remained stable for diarrhea and/or flushing. For DB
      placebo patients, composite scores for diarrhea, flushing, and diarrhea and/or
      flushing improved significantly between DB and IOL treatment (mean differences: 
      1.07 [-1.65 to -0.49]; -1.06 [-1.93 to -0.19]; and -2.13 [-3.35 to -0.91]; all p
      <= .018). CONCLUSION: Improved diarrhea and flushing control in CS patients
      during 16-week lanreotide treatment was sustained during maintenance of
      lanreotide treatment for the 32-week IOL phase (48 weeks total). IMPLICATIONS FOR
      PRACTICE: This study prospectively collected daily patient-reported data on
      diarrhea and flushing from the ELECT trial to evaluate the direct impact of
      lanreotide depot on patients' relief of carcinoid syndrome symptoms. Treatment
      with lanreotide depot was associated with significant reductions in the
      percentages of days patients reported symptoms of diarrhea and flushing, as well
      as reductions in the frequency and severity of daily symptoms compared with
      placebo during 16 weeks of double-blind treatment. These improvements were
      sustained for 32 additional weeks of open-label lanreotide treatment (i.e.,
      through week 48 of treatment), resulting in clinically meaningful, long-term
      symptom reduction.

PMID- 29038235
TI  - Rare Tumor Clinic: The University of California San Diego Moores Cancer Center
      Experience with a Precision Therapy Approach.
AB  - BACKGROUND: Patients with rare tumors may lack approved treatments and clinical
      trial access. Although each rare tumor is uncommon, cumulatively they account for
      approximately 25% of cancers. We recently initiated a Rare Tumor Clinic that
      emphasized a precision medicine strategy. MATERIALS AND METHODS: We investigated
      the first 40 patients presenting at the Rare Tumor Clinic. Next-generation
      sequencing (NGS) of tissue and plasma-derived, circulating-tumor DNA (ctDNA), and
      protein markers were assessed. RESULTS: Median age was 58 years (range, 31-78
      years); 70% (28/40) were women; median number of previous systemic therapies was
      2 (range 0-7). The most common diagnoses were sarcoma (n = 7) for solid tumors
      and Erdheim-Chester disease (n = 5) for hematologic malignancies. Twenty distinct
      diagnoses were seen. Examples of ultrarare tumors included ameloblastoma, yolk
      sac liver tumor, ampullary cancer, and Castleman's disease. Altogether, 32 of 33
      patients (97%) with tissue NGS and 15 of 33 (45%) with ctDNA sequencing harbored
      >=1 alteration. Overall, 92.5% of patients (37/40) had >=1 actionable target
      based on either genomic (n = 32) or protein (n = 27) markers. In total, 52.5%
      (21/40) received matched therapy; 52.4% (11/21) achieved stable disease (SD) >=6
      months (n = 3), partial remission (PR; n = 6), or complete remission (CR; n = 2).
      Matched therapy resulted in significantly longer progression-free survival
      compared with last prior unmatched therapy (hazard ratio 0.26, 95% confidence
      interval 0.10-0.71, p = .008). CONCLUSION: Identifying genomic and protein
      markers in patients with rare/ultrarare tumors was feasible. When therapies were
      matched, >50% of patients attained SD >=6 months, PR, or CR. Further precision
      medicine clinical investigations focusing on rare and ultrarare tumors are
      urgently needed. IMPLICATIONS FOR PRACTICE: Although rare tumors are infrequent
      by definition, when all subtypes of rare cancers are combined, they account for
      approximately 25% of adult malignancies. However, patients with rare tumors may
      lack approved treatments and clinical trial access. This paper describes an
      institutional a Rare Tumor Clinic focused on a precision medicine strategy.
      Performing genomics and protein analyses was feasible amongst patients with rare
      cancers. Over 50% of patients attained SD >=6 months, PR, or CR when they
      received matched therapy (genomically targeted and/or immunotherapy). Further
      studies investigating the efficacy of the precision therapy approach among rare
      tumors are warranted.

PMID- 29038236
TI  - Efficacy of Prophylactic Treatment for Oxycodone-Induced Nausea and Vomiting
      Among Patients with Cancer Pain (POINT): A Randomized, Placebo-Controlled, Double
      Blind Trial.
AB  - BACKGROUND: Although opioid-induced nausea and vomiting (OINV) often result in
      analgesic undertreatment in patients with cancer, no randomized controlled trials
      have evaluated the efficacy of prophylactic antiemetics for preventing OINV. We
      conducted this randomized, placebo-controlled, double-blind trial to evaluate the
      efficacy and safety of prophylactic treatment with prochlorperazine for
      preventing OINV. MATERIALS AND METHODS: Cancer patients who started to receive
      oral oxycodone were randomly assigned in a 1:1 ratio to receive either
      prochlorperazine 5 mg or placebo prophylactically, given three times daily for 5
      days. The primary endpoint was the proportion of patients who had a complete
      response (CR) during the 120 hours of oxycodone treatment. CR was defined as no
      emetic episode and no use of rescue medication for nausea and vomiting during 5
      days. Key secondary endpoints were the proportion of patients with emetic
      episodes, proportion of patients with moderate or severe nausea, quality of life,
      and proportion of treatment withdrawal. RESULTS: From November 2013 through
      February 2016, a total of 120 patients were assigned to receive prochlorperazine
      (n = 60) or placebo (n = 60). There was no significant difference in CR rates
      (69.5% vs. 63.3%; p = .47) or any secondary endpoint between the groups. Patients
      who received prochlorperazine were more likely to experience severe somnolence (p
      = .048). CONCLUSION: Routine use of prochlorperazine as a prophylactic antiemetic
      at the initiation of treatment with opioids is not recommended. Further research
      is needed to evaluate whether other antiemetics would be effective in preventing
      OINV in specific patient populations. IMPLICATIONS FOR PRACTICE: Prophylactic
      prochlorperazine seems to be ineffective in preventing opioid-induced nausea and
      vomiting (OINV) and may cause adverse events such as somnolence. Routine use of
      prophylactic prochlorperazine at the initiation of treatment with opioids is not
      recommended. Further research is needed to evaluate whether other antiemetics
      would be effective in preventing OINV in specific patient populations.

PMID- 29038237
TI  - The Gain-of-Function Integrin beta3 Pro33 Variant Alters the Serotonin System in
      the Mouse Brain.
AB  - Engagement of integrins by the extracellular matrix initiates signaling cascades
      that drive a variety of cellular functions, including neuronal migration and
      axonal pathfinding in the brain. Multiple lines of evidence link the ITGB3 gene
      encoding the integrin beta3 subunit with the serotonin (5-HT) system, likely via
      its modulation of the 5-HT transporter (SERT). The ITGB3 coding polymorphism
      Leu33Pro (rs5918, PlA2) produces hyperactive alphavbeta3 receptors that influence
      whole-blood 5-HT levels and may influence the risk for autism spectrum disorder
      (ASD). Using a phenome-wide scan of psychiatric diagnoses, we found significant,
      male-specific associations between the Pro33 allele and attention-deficit
      hyperactivity disorder and ASDs. Here, we used knock-in (KI) mice expressing an
      Itgb3 variant that phenocopies the human Pro33 variant to elucidate the
      consequences of constitutively enhanced alphavbeta3 signaling to the 5-HT system
      in the brain. KI mice displayed deficits in multiple behaviors, including
      anxiety, repetitive, and social behaviors. Anatomical studies revealed a
      significant decrease in 5-HT synapses in the midbrain, accompanied by decreases
      in SERT activity and reduced localization of SERTs to integrin adhesion complexes
      in synapses of KI mice. Inhibition of focal adhesion kinase (FAK) rescued SERT
      function in synapses of KI mice, demonstrating that constitutive active FAK
      signaling downstream of the Pro32Pro33 integrin alphavbeta3 suppresses SERT
      activity. Our studies identify a complex regulation of 5-HT homeostasis and
      behaviors by integrin alphavbeta3, revealing an important role for integrins in
      modulating risk for neuropsychiatric disorders.SIGNIFICANCE STATEMENT The
      integrin beta3 Leu33Pro coding polymorphism has been associated with autism
      spectrum disorders (ASDs) within a subgroup of patients with elevated blood 5-HT
      levels, linking integrin beta3, 5-HT, and ASD risk. We capitalized on these
      interactions to demonstrate that the Pro33 coding variation in the murine
      integrin beta3 recapitulates the sex-dependent neurochemical and behavioral
      attributes of ASD. Using state-of-the-art techniques, we show that presynaptic 5
      HT function is altered in these mice, and that the localization of 5-HT
      transporters to specific compartments within the synapse, disrupted by the
      integrin beta3 Pro33 mutation, is critical for appropriate reuptake of 5-HT. Our
      studies provide fundamental insight into the genetic network regulating 5-HT
      neurotransmission in the CNS that is also associated with ASD risk.

PMID- 29038238
TI  - Delayed Maturation of Fast-Spiking Interneurons Is Rectified by Activation of the
      TrkB Receptor in the Mouse Model of Fragile X Syndrome.
AB  - Fragile X syndrome (FXS) is a neurodevelopmental disorder that is a leading cause
      of inherited intellectual disability, and the most common known cause of autism
      spectrum disorder. FXS is broadly characterized by sensory hypersensitivity and
      several developmental alterations in synaptic and circuit function have been
      uncovered in the sensory cortex of the mouse model of FXS (Fmr1 KO). GABA
      mediated neurotransmission and fast-spiking (FS) GABAergic interneurons are
      central to cortical circuit development in the neonate. Here we demonstrate that
      there is a delay in the maturation of the intrinsic properties of FS interneurons
      in the sensory cortex, and a deficit in the formation of excitatory synaptic
      inputs on to these neurons in neonatal Fmr1 KO mice. Both these delays in
      neuronal and synaptic maturation were rectified by chronic administration of a
      TrkB receptor agonist. These results demonstrate that the maturation of the
      GABAergic circuit in the sensory cortex is altered during a critical
      developmental period due in part to a perturbation in BDNF-TrkB signaling, and
      could contribute to the alterations in cortical development underlying the
      sensory pathophysiology of FXS.SIGNIFICANCE STATEMENT Fragile X (FXS) individuals
      have a range of sensory related phenotypes, and there is growing evidence of
      alterations in neuronal circuits in the sensory cortex of the mouse model of FXS
      (Fmr1 KO). GABAergic interneurons are central to the correct formation of
      circuits during cortical critical periods. Here we demonstrate a delay in the
      maturation of the properties and synaptic connectivity of interneurons in Fmr1 KO
      mice during a critical period of cortical development. The delays both in
      cellular and synaptic maturation were rectified by administration of a TrkB
      receptor agonist, suggesting reduced BDNF-TrkB signaling as a contributing
      factor. These results provide evidence that the function of fast-spiking
      interneurons is disrupted due to a deficiency in neurotrophin signaling during
      early development in FXS.

PMID- 29038239
TI  - Correlated Disruption of Resting-State fMRI, LFP, and Spike Connectivity between
      Area 3b and S2 following Spinal Cord Injury in Monkeys.
AB  - This study aims to understand how functional connectivity (FC) between areas 3b
      and S2 alters following input deprivation and the neuronal basis of disrupted FC
      of resting-state fMRI signals. We combined submillimeter fMRI with microelectrode
      recordings to localize the deafferented digit regions in areas 3b and S2 by
      mapping tactile stimulus-evoked fMRI activations before and after cervical dorsal
      column lesion in each male monkey. An average afferent disruption of 97%
      significantly reduced fMRI, local field potential (LFP), and spike responses to
      stimuli in both areas. Analysis of resting-state fMRI signal correlation, LFP
      coherence, and spike cross-correlation revealed significantly reduced functional
      connectivity between deafferented areas 3b and S2. The degrees of reductions in
      stimulus responsiveness and FC after deafferentation differed across fMRI, LFP,
      and spiking signals. The reduction of FC was much weaker than that of stimulus
      evoked responses. Whereas the largest stimulus-evoked signal drop (~80%) was
      observed in LFP signals, the greatest FC reduction was detected in the spiking
      activity (~30%). fMRI signals showed mild reductions in stimulus responsiveness
      (~25%) and FC (~20%). The overall deafferentation-induced changes were quite
      similar in areas 3b and S2 across signals. Here we demonstrated that FC strength
      between areas 3b and S2 was much weakened by dorsal column lesion, and stimulus
      response reduction and FC disruption in fMRI covary with those of LFP and spiking
      signals in deafferented areas 3b and S2. These findings have important
      implications for fMRI studies aiming to probe FC alterations in pathological
      conditions involving deafferentation in humans.SIGNIFICANCE STATEMENT By directly
      comparing fMRI, local field potential, and spike signals in both tactile
      stimulation and resting states before and after severe disruption of dorsal
      column afferent, we demonstrated that reduction in fMRI responses to stimuli is
      accompanied by weakened resting-state fMRI functional connectivity (FC) in input
      deprived and reorganized digit regions in area 3b of the S1 and S2. Concurrent
      reductions in local field potential and spike FC validated the use of resting
      state fMRI signals for probing neural intrinsic FC alterations in pathological
      deafferented cortex, and indicated that disrupted FC between mesoscale
      functionally highly related regions may contribute to the behavioral impairments.

PMID- 29038240
TI  - alphaII Spectrin Forms a Periodic Cytoskeleton at the Axon Initial Segment and Is
      Required for Nervous System Function.
AB  - Spectrins form a submembranous cytoskeleton proposed to confer strength and
      flexibility to neurons and to participate in ion channel clustering at axon
      initial segments (AIS) and nodes of Ranvier. Neuronal spectrin cytoskeletons
      consist of diverse beta subunits and alphaII spectrin. Although alphaII spectrin
      is found in neurons in both axonal and somatodendritic domains, using proteomics,
      biochemistry, and superresolution microscopy, we show that alphaII and betaIV
      spectrin interact and form a periodic AIS cytoskeleton. To determine the role of
      spectrins in the nervous system, we generated Sptan1f/f mice for deletion of CNS
      alphaII spectrin. We analyzed alphaII spectrin-deficient mice of both sexes and
      found that loss of alphaII spectrin causes profound reductions in all beta
      spectrins. alphaII spectrin-deficient mice die before 1 month of age and have
      disrupted AIS and many other neurological impairments including seizures,
      disrupted cortical lamination, and widespread neurodegeneration. These results
      demonstrate the importance of the spectrin cytoskeleton both at the AIS and
      throughout the nervous system.SIGNIFICANCE STATEMENT Spectrin cytoskeletons play
      diverse roles in neurons, including assembly of excitable domains such as the
      axon initial segment (AIS) and nodes of Ranvier. However, the molecular
      composition and structure of these cytoskeletons remain poorly understood. Here,
      we show that alphaII spectrin partners with betaIV spectrin to form a periodic
      cytoskeleton at the AIS. Using a new alphaII spectrin conditional knock-out
      mouse, we show that alphaII spectrin is required for AIS assembly, neuronal
      excitability, cortical lamination, and to protect against neurodegeneration.
      These results demonstrate the broad importance of spectrin cytoskeletons for
      nervous system function and development and have important implications for
      nervous system injuries and diseases because disruption of the spectrin
      cytoskeleton is a common molecular pathology.

PMID- 29038241
TI  - Sensorimotor Processing in the Basal Ganglia Leads to Transient Beta Oscillations
      during Behavior.
AB  - Brief epochs of beta oscillations have been implicated in sensorimotor control in
      the basal ganglia of task-performing healthy animals. However, which neural
      processes underlie their generation and how they are affected by sensorimotor
      processing remains unclear. To determine the mechanisms underlying transient beta
      oscillations in the LFP, we combined computational modeling of the subthalamo
      pallidal network for the generation of beta oscillations with realistic
      stimulation patterns derived from single-unit data recorded from different basal
      ganglia subregions in rats performing a cued choice task. In the recordings, we
      found distinct firing patterns in the striatum, globus pallidus, and subthalamic
      nucleus related to sensory and motor events during the behavioral task. Using
      these firing patterns to generate realistic inputs to our network model led to
      transient beta oscillations with the same time course as the rat LFP data. In
      addition, our model can account for further nonintuitive aspects of beta
      modulation, including beta phase resets after sensory cues and correlations with
      reaction time. Overall, our model can explain how the combination of temporally
      regulated sensory responses of the subthalamic nucleus, ramping activity of the
      subthalamic nucleus, and movement-related activity of the globus pallidus leads
      to transient beta oscillations during behavior.SIGNIFICANCE STATEMENT Transient
      beta oscillations emerge in the normal functioning cortico-basal ganglia loop
      during behavior. Here, we used a unique approach connecting a computational model
      closely with experimental data. In this way, we achieved a simulation environment
      for our model that mimics natural input patterns in awake, behaving animals. We
      demonstrate that a computational model for beta oscillations in Parkinson's
      disease (PD) can also account for complex patterns of transient beta oscillations
      in healthy animals. Therefore, we propose that transient beta oscillations in
      healthy animals share the same mechanism with pathological beta oscillations in
      PD. This important result connects functional and pathological roles of beta
      oscillations in the basal ganglia.

PMID- 29038242
TI  - Activity-Dependent Facilitation of CaV1.3 Calcium Channels Promotes KCa3.1
      Activation in Hippocampal Neurons.
AB  - CaV1 L-type calcium channels are key to regulating neuronal excitability, with
      the range of functional roles enhanced by interactions with calmodulin, accessory
      proteins, or CaMKII that modulate channel activity. In hippocampal pyramidal
      cells, a prominent elevation of CaV1 activity is apparent in late channel
      openings that can last for seconds following a depolarizing stimulus train. The
      current study tested the hypothesis that a reported interaction among CaV1.3
      channels, the scaffolding protein densin, and CaMKII could generate a
      facilitation of channel activity that outlasts a depolarizing stimulus. We found
      that CaV1.3 but not CaV1.2 channels exhibit a long-duration calcium-dependent
      facilitation (L-CDF) that lasts up to 8 s following a brief 50 Hz stimulus train,
      but only when coexpressed with densin and CaMKII. To test the physiological role
      for CaV1.3 L-CDF, we coexpressed the intermediate-conductance KCa3.1 potassium
      channel, revealing a strong functional coupling to CaV1.3 channel activity that
      was accentuated by densin and CaMKII. Moreover, the CaV1.3-densin-CaMKII
      interaction gave rise to an outward tail current of up to 8 s duration following
      a depolarizing stimulus in both tsA-201 cells and male rat CA1 pyramidal cells. A
      slow afterhyperpolarization in pyramidal cells was reduced by a selective block
      of CaV1 channels by isradipine, a CaMKII blocker, and siRNA knockdown of densin,
      and spike frequency increased upon selective block of CaV1 channel conductance.
      The results are important in revealing a CaV1.3-densin-CaMKII interaction that
      extends the contribution of CaV1.3 calcium influx to a time frame well beyond a
      brief input train.SIGNIFICANCE STATEMENT CaV1 L-type calcium channels play a key
      role in regulating the output of central neurons by providing calcium influx
      during repetitive inputs. This study identifies a long-duration calcium-dependent
      facilitation (L-CDF) of CaV1.3 channels that depends on the scaffolding protein
      densin and CaMKII and that outlasts a depolarizing stimulus by seconds. We
      further show a tight functional coupling between CaV1.3 calcium influx and the
      intermediate-conductance KCa3.1 potassium channel that promotes an outward tail
      current of up to 8 s following a depolarizing stimulus. Tests in CA1 hippocampal
      pyramidal cells reveal that a slow AHP is reduced by blocking different
      components of the CaV1.3-densin-CaMKII interaction, identifying an important role
      for CaV1.3 L-CDF in regulating neuronal excitability.

PMID- 29038243
TI  - An alphaII Spectrin-Based Cytoskeleton Protects Large-Diameter Myelinated Axons
      from Degeneration.
AB  - Axons must withstand mechanical forces, including tension, torsion, and
      compression. Spectrins and actin form a periodic cytoskeleton proposed to protect
      axons against these forces. However, because spectrins also participate in
      assembly of axon initial segments (AISs) and nodes of Ranvier, it is difficult to
      uncouple their roles in maintaining axon integrity from their functions at AIS
      and nodes. To overcome this problem and to determine the importance of spectrin
      cytoskeletons for axon integrity, we generated mice with alphaII spectrin
      deficient peripheral sensory neurons. The axons of these neurons are very long
      and exposed to the mechanical forces associated with limb movement; most lack an
      AIS, and some are unmyelinated and have no nodes. We analyzed alphaII spectrin
      deficient mice of both sexes and found that, in myelinated axons, alphaII
      spectrin forms a periodic cytoskeleton with betaIV and betaII spectrin at nodes
      of Ranvier and paranodes, respectively, but that loss of alphaII spectrin
      disrupts this organization. Avil-cre;Sptan1f/f mice have reduced numbers of
      nodes, disrupted paranodal junctions, and mislocalized Kv1 K+ channels. We show
      that the density of nodal betaIV spectrin is constant among axons, but the
      density of nodal alphaII spectrin increases with axon diameter. Remarkably, Avil
      cre;Sptan1f/f mice have intact nociception and small-diameter axons, but severe
      ataxia due to preferential degeneration of large-diameter myelinated axons. Our
      results suggest that nodal alphaII spectrin helps resist the mechanical forces
      experienced by large-diameter axons, and that alphaII spectrin-dependent
      cytoskeletons are also required for assembly of nodes of Ranvier.SIGNIFICANCE
      STATEMENT A periodic axonal cytoskeleton consisting of actin and spectrin has
      been proposed to help axons resist the mechanical forces to which they are
      exposed (e.g., compression, torsion, and stretch). However, until now, no
      vertebrate animal model has tested the requirement of the spectrin cytoskeleton
      in maintenance of axon integrity. We demonstrate the role of the periodic
      spectrin-dependent cytoskeleton in axons and show that loss of alphaII spectrin
      from PNS axons causes preferential degeneration of large-diameter myelinated
      axons. We show that nodal alphaII spectrin is found at greater densities in large
      diameter myelinated axons, suggesting that nodes are particularly vulnerable
      domains requiring a specialized cytoskeleton to protect against axon
      degeneration.

PMID- 29038244
TI  - Overactivity of Liver-Related Neurons in the Paraventricular Nucleus of the
      Hypothalamus: Electrophysiological Findings in db/db Mice.
AB  - Preautonomic neurons in the paraventricular nucleus (PVN) of the hypothalamus
      play a large role in the regulation of hepatic functions via the autonomic
      nervous system. Activation of hepatic sympathetic nerves increases glucose and
      lipid metabolism and contributes to the elevated hepatic glucose production
      observed in the type 2 diabetic condition. This augmented sympathetic output
      could originate from altered activity of liver-related PVN neurons. Remarkably,
      despite the importance of the brain-liver pathway, the cellular properties of
      liver-related neurons are not known. In this study, we provide the first evidence
      of overall activity of liver-related PVN neurons. Liver-related PVN neurons were
      identified with a retrograde, trans-synaptic, viral tracer in male lean and db/db
      mice and whole-cell patch-clamp recordings were conducted. In db/db mice, the
      majority of liver-related PVN neurons fired spontaneously; whereas, in lean mice
      the majority of liver-related PVN neurons were silent, indicating that liver
      related PVN neurons are more active in db/db mice. Persistent, tonic inhibition
      was identified in liver-related PVN neurons; although, the magnitude of tonic
      inhibitory control was not different between lean and db/db mice. In addition,
      our study revealed that the transient receptor potential vanilloid type 1
      dependent increase of excitatory neurotransmission was reduced in liver-related
      PVN neurons of db/db mice. These findings demonstrate plasticity of liver-related
      PVN neurons and a shift toward excitation in a diabetic mouse model. Our study
      suggests altered autonomic circuits at the level of the PVN, which can contribute
      to autonomic dysfunction and dysregulation of neural control of hepatic functions
      including glucose metabolism.SIGNIFICANCE STATEMENT A growing body of evidence
      suggests the importance of the autonomic control in the regulation of hepatic
      metabolism, which plays a major role in the development and progression of type 2
      diabetes mellitus. Despite the importance of the brain-liver pathway, the overall
      activity of liver-related neurons in control and diabetic conditions is not
      known. This is a significant gap in knowledge, which prevents developing
      strategies to improve glucose homeostasis via altering the brain-liver pathway.
      One of the key findings of our study is the overall shift toward excitation in
      liver-related hypothalamic neurons in the diabetic condition. This overactivity
      may be one of the underlying mechanisms of elevated sympathetic activity known in
      metabolically compromised patients and animal models.

PMID- 29038245
TI  - Mitochondrial Calcium Dysregulation Contributes to Dendrite Degeneration Mediated
      by PD/LBD-Associated LRRK2 Mutants.
AB  - Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to development of
      late-onset familial Parkinson's disease (PD), with clinical features of motor and
      cognitive dysfunction indistinguishable from sporadic PD. Calcium dysregulation
      plays an important role in PD pathogenesis, but the mechanisms of
      neurodegeneration remain unclear. Recent reports indicate enhanced excitatory
      neurotransmission in cortical neurons expressing mutant LRRK2, which occurs
      before the well-characterized phenotype of dendritic shortening. As mitochondria
      play a major role in the rapid buffering of cytosolic calcium, we hypothesized
      that altered mitochondrial calcium handling contributes to dendritic retraction
      elicited by the LRRK2-G2019S and -R1441C mutations. In primary mouse cortical
      neurons, we observed increased depolarization-induced mitochondrial calcium
      uptake. We found that expression of mutant LRRK2 elicited transcriptional
      upregulation of the mitochondrial calcium uniporter (MCU) and the mitochondrial
      calcium uptake 1 protein (MICU1) with no change in levels of the mitochondrial
      calcium antiporter NCLX. Elevated MCU and MICU1 were also observed in LRRK2
      mutated patient fibroblasts, along with increased mitochondrial calcium uptake,
      and in postmortem brains of sporadic PD/PDD patients of both sexes.
      Transcriptional upregulation of MCU and MICU1 was caused by activation of the
      ERK1/2 (MAPK3/1) pathway. Inhibiting ERK1/2 conferred protection against mutant
      LRRK2-induced neurite shortening. Pharmacological inhibitors or RNAi knockdown of
      MCU attenuated mitochondrial calcium uptake and dendritic/neuritic shortening
      elicited by mutant LRRK2, whereas expression of a constitutively active mutant of
      NCLX that enhances calcium export from mitochondria was neuroprotective. These
      data suggest that an increased susceptibility to mitochondrial calcium
      dysregulation contributes to dendritic injury in mutant LRRK2
      pathogenesis.SIGNIFICANCE STATEMENT Cognitive dysfunction and dementia are common
      features of Parkinson's disease (PD), causing significant disability. Mutations
      in LRRK2 represent the most common known genetic cause of PD. We found that PD
      linked LRRK2 mutations increased dendritic and mitochondrial calcium uptake in
      cortical neurons and familial PD patient fibroblasts, accompanied by increased
      expression of the mitochondrial calcium transporter MCU. Blocking the ERK1/2
      dependent upregulation of MCU conferred protection against mutant LRRK2-elicited
      dendrite shortening, as did inhibiting MCU-mediated calcium import. Conversely,
      stimulating the export of calcium from mitochondria was also neuroprotective.
      These results implicate increased susceptibility to mitochondrial calcium
      overload in LRRK2-driven neurodegeneration, and suggest possible interventions
      that may slow the progression of cognitive dysfunction in PD.

PMID- 29038246
TI  - CB1-Dependent Long-Term Depression in Ventral Tegmental Area GABA Neurons: A
      Novel Target for Marijuana.
AB  - The VTA is necessary for reward behavior with dopamine cells critically involved
      in reward signaling. Dopamine cells in turn are innervated and regulated by
      neighboring inhibitory GABA cells. Using whole-cell electrophysiology in juvenile
      adolescent GAD67-GFP male mice, we examined excitatory plasticity in fluorescent
      VTA GABA cells. A novel CB1-dependent LTD was induced in GABA cells that was
      dependent on metabotropic glutamate receptor 5, and cannabinoid receptor 1 (CB1).
      LTD was absent in CB1 knock-out mice but preserved in heterozygous littermates.
      Bath applied Delta9-tetrahydrocannabinol depressed GABA cell activity, therefore
      downstream dopamine cells will be disinhibited; and thus, this could potentially
      result in increased reward. Chronic injections of Delta9-tetrahydrocannabinol
      occluded LTD compared with vehicle injections; however, a single exposure was
      insufficient to do so. As synaptic modifications by drugs of abuse are often tied
      to addiction, these data suggest a possible mechanism for the addictive effects
      of Delta9-tetrahydrocannabinol in juvenile-adolescents, by potentially altering
      reward behavioral outcomes.SIGNIFICANCE STATEMENT The present study identifies a
      novel form of glutamatergic synaptic plasticity in VTA GABA neurons, a currently
      understudied cell type that is critical for the brain's reward circuit, and how
      Delta9-tetrahydrocannabinol occludes this plasticity. This study specifically
      addresses a potential unifying mechanism whereby marijuana could exert rewarding
      and addictive/withdrawal effects. Marijuana use and legalization are a pressing
      issue for many states in the United States. Although marijuana is the most
      commonly abused illicit drug, the implications of legalized, widespread, or
      continued usage are speculative. This study in juvenile-adolescent aged mice
      identifies a novel form of synaptic plasticity in VTA GABA cells, and the
      synaptic remodeling that can occur after Delta9-tetrahydrocannabinol use.

PMID- 29038247
TI  - Constitutive Activation of Integrin alpha9 Augments Self-Directed Hyperplastic
      and Proinflammatory Properties of Fibroblast-like Synoviocytes of Rheumatoid
      Arthritis.
AB  - Despite advances in the treatment of rheumatoid arthritis (RA), currently
      approved medications can have significant side effects due to their direct
      immunosuppressive activities. Additionally, current therapies do not address
      residual synovial inflammation. In this study, we evaluated the role of integrin
      alpha9 and its ligand, tenascin-C (Tn-C), on the proliferative and inflammatory
      response of fibroblast-like synoviocytes (FLSs) from RA patients grown in three
      dimensional (3D)-micromass culture. FLSs from osteoarthritis patients, when grown
      in the 3D-culture system, formed self-directed lining-like structures, whereas
      FLSs from RA tissues (RA-FLSs) developed an abnormal structure of condensed
      cellular accumulation reflective of the pathogenic features of RA synovial
      tissues. Additionally, RA-FLSs grown in 3D culture showed autonomous production
      of proinflammatory mediators. Predominant expression of alpha9 and Tn-C was
      observed in the condensed lining, and knockdown of these molecules abrogated the
      abnormal lining-like structure formation and suppressed the spontaneous
      expression of matrix metalloproteinases, IL-6, TNFSF11/RANKL, and cadherin-11.
      Disruption of alpha9 also inhibited expression of Tn-C, suggesting existence of a
      positive feedback loop in which the engagement of alpha9 with Tn-C self-amplifies
      its own signaling and promotes progression of synovial hyperplasia. Depletion of
      alpha9 also suppressed the platelet-derived growth factor-induced hyperplastic
      response of RA-FLSs and blunted the TNF-alpha-induced expression of matrix
      metalloproteinases and IL-6. Finally, alpha9-blocking Ab also suppressed the
      formation of the condensed cellular lining by RA-FLSs in 3D cultures in a
      concentration-related manner. This study demonstrates the central role of alpha9
      in pathogenic behaviors of RA-FLSs and highlights the potential of alpha9
      blocking agents as a nonimmunosuppressive treatment for RA-associated synovitis.

PMID- 29038248
TI  - Lipopolysaccharide Potentiates Insulin-Driven Hypoglycemic Shock.
AB  - Critically ill patients typically present with hyperglycemia. Treatment with
      conventional insulin therapy (targeting 144-180 mg/dl) improves patient survival;
      however, intensive insulin therapy (IIT) targeting normal blood glucose levels
      (81-108 mg/dl) increases the incidence of moderate and severe hypoglycemia, and
      increases mortality. Septic patients are especially prone to IIT-induced
      hypoglycemia, but the mechanism remains unknown. Here, we show that codelivery of
      insulin with otherwise sublethal doses of LPS induced hypoglycemic shock in mice
      within 1-2 h. LPS impaired clearance of insulin, which amplified insulin receptor
      signaling. These effects were mediated by caspase-11, TLR4, and complement, each
      of which trigger eicosanoid production that potentiates insulin signaling.
      Finally, in an animal model of sepsis, we observed that Salmonella typhimurium
      infected mice exhibited simultaneous impaired insulin clearance coexisting with
      insulin resistance. Our results raise the possibility that septic patients have
      impaired insulin clearance, which could increase their susceptibility to
      hypoglycemia during IIT, contraindicating its use.

PMID- 29038249
TI  - Anti-PD-1 Antibody Treatment Promotes Clearance of Persistent Cryptococcal Lung
      Infection in Mice.
AB  - Activation of immunomodulatory pathways in response to invasive fungi can impair
      clearance and promote persistent infections. The programmed cell death protein-1
      (PD-1) signaling pathway inhibits immune effector responses against tumors, and
      immune checkpoint inhibitors that block this pathway are being increasingly used
      as cancer therapy. The objective of this study was to investigate whether this
      pathway contributes to persistent fungal infection and to determine whether anti
      PD-1 Ab treatment improves fungal clearance. Studies were performed using C57BL/6
      mice infected with a moderately virulent strain of Cryptococcus neoformans (52D),
      which resulted in prolonged elevations in fungal burden and histopathologic
      evidence of chronic lung inflammation. Persistent infection was associated with
      increased and sustained expression of PD-1 on lung lymphocytes, including a mixed
      population of CD4+ T cells. In parallel, expression of the PD-1 ligands, PD-1
      ligands 1 and 2, was similarly upregulated on specific subsets of resident and
      recruited lung dendritic cells and macrophages. Treatment of persistently
      infected mice for 4 wk by repetitive administration of neutralizing anti-PD-1 Ab
      significantly improved pulmonary fungal clearance. Treatment was well tolerated
      without evidence of morbidity. Immunophenotyping revealed that anti-PD-1 Ab
      treatment did not alter immune effector cell numbers or myeloid cell activation.
      Treatment did reduce gene expression of IL-5 and IL-10 by lung leukocytes and
      promoted sustained upregulation of OX40 by Th1 and Th17 cells. Collectively, this
      study demonstrates that PD-1 signaling promotes persistent cryptococcal lung
      infection and identifies this pathway as a potential target for novel immune
      based treatments of chronic fungal disease.

PMID- 29038250
TI  - Inhibition of IRAK1 Ubiquitination Determines Glucocorticoid Sensitivity for TLR9
      Induced Inflammation in Macrophages.
AB  - Inflammatory responses are controlled by signaling mediators that are regulated
      by various posttranslational modifications. Recently, transcription-independent
      functions for glucocorticoids (GC) in restraining inflammation have emerged, but
      the underlying mechanisms are unknown. In this study, we report that GC receptor
      (GR)-mediated actions of GC acutely suppress TLR9-induced inflammation via
      inhibition of IL-1R-associated kinase 1 (IRAK1) ubiquitination. beta-TrCP-IRAK1
      interaction is required for K48-linked ubiquitination of IRAK1 at Lys134 and
      subsequent membrane-to-cytoplasm trafficking of IRAK1 interacting partners TNFR
      associated factor 6 and TAK1 that facilitates NF-kappaB and MAPK activation. Upon
      costimulation of macrophages with GC and TLR9-engaging ligand, GR physically
      interacts with IRAK1 and interferes with protein-protein interactions between
      beta-TrCP and IRAK1. Ablation of GR in macrophages prevents GC-dependent
      suppression of beta-TrCP-IRAK1 interactions. This GC-mediated suppression of
      IRAK1 activation is unique to TLR9, as GC treatment impairs TLR9 but not TLR4
      ligand-induced K48-linked IRAK1 ubiquitination and trafficking of IRAK1
      interacting partners. Furthermore, mutations in IRAK1 at Lys134 prevent TLR9
      ligand-induced activation of inflammatory signaling mediators and synthesis of
      proinflammatory cytokines to an extent comparable to GC-mediated inhibition.
      Collectively, these findings identify a transcription-independent, rapid, and
      nongenomic GC suppression of TLR9 ligand-mediated IRAK1 ubiquitination as a novel
      mechanism for restraining acute inflammatory reactions.

PMID- 29038251
TI  - Stress Introduction Rate Alters the Benefit of AcrAB-TolC Efflux Pumps.
AB  - Stress tolerance studies are typically conducted in an all-or-none fashion.
      However, in realistic settings-such as in clinical or metabolic engineering
      applications-cells may encounter stresses at different rates. Therefore, how
      cells tolerate stress may depend on its rate of appearance. To address this, we
      studied how the rate of stress introduction affects bacterial stress tolerance by
      focusing on a key stress response mechanism. Efflux pumps, such as AcrAB-TolC of
      Escherichia coli, are membrane transporters well known for the ability to export
      a wide variety of substrates, including antibiotics, signaling molecules, and
      biofuels. Although efflux pumps improve stress tolerance, pump overexpression can
      result in a substantial fitness cost to the cells. We hypothesized that the ideal
      pump expression level would involve a rate-dependent trade-off between the
      benefit of pumps and the cost of their expression. To test this, we evaluated the
      benefit of the AcrAB-TolC pump under different rates of stress introduction,
      including a step, a fast ramp, and a gradual ramp. Using two chemically diverse
      stresses, the antibiotic chloramphenicol and the jet biofuel precursor pinene, we
      assessed the benefit provided by the pumps. A mathematical model describing these
      effects predicted the benefit as a function of the rate of stress introduction.
      Our findings demonstrate that as the rate of introduction is lowered, stress
      response mechanisms provide a disproportionate benefit to pump-containing
      strains, allowing cells to survive beyond the original inhibitory
      concentrations.IMPORTANCE Efflux pumps are ubiquitous in nature and provide
      stress tolerance in the cells of species ranging from bacteria to mammals.
      Understanding how pumps provide tolerance has far-reaching implications for
      diverse fields, from medicine to biotechnology. Here, we investigated how the
      rate of stressor appearance impacts tolerance. We focused on two distinct
      substrates of AcrAB-TolC efflux pumps, the antibiotic chloramphenicol and the
      biofuel precursor pinene. Interestingly, tolerance is highly dependent on the
      rate of stress introduction. Therefore, it is important to consider not only the
      total quantity of a stressor but also the rate at which it is applied. The
      implications of this work are significant because environments are rarely static;
      antibiotic concentrations change during dosing, and metabolic engineering
      processes change with time.

PMID- 29038252
TI  - A Bacteriophage Capsid Protein Is an Inhibitor of a Conserved Transcription
      Terminator of Various Bacterial Pathogens.
AB  - Rho is a hexameric molecular motor that functions as a conserved transcription
      terminator in the majority of bacterial species and is a potential drug target.
      Psu is a bacteriophage P4 capsid protein that inhibits Escherichia coli Rho by
      obstructing its ATPase and translocase activities. In this study, we explored the
      anti-Rho activity of Psu for Rho proteins from different pathogens. Sequence
      alignment and homology modeling of Rho proteins from pathogenic bacteria revealed
      the conserved nature of the Psu-interacting regions in all these proteins. We
      chose Rho proteins from various pathogens, including Mycobacterium smegmatis,
      Mycobacterium bovis, Mycobacterium tuberculosis, Xanthomonas campestris,
      Xanthomonas oryzae, Corynebacterium glutamicum, Vibrio cholerae, Salmonella
      enterica, and Pseudomonas syringae The purified recombinant Rho proteins of these
      organisms showed variable rates of ATP hydrolysis on poly(rC) as the substrate
      and were capable of releasing RNA from the E. coli transcription elongation
      complexes. Psu was capable of inhibiting these two functions of all these Rho
      proteins. In vivo pulldown assays revealed direct binding of Psu with many of
      these Rho proteins. In vivo expression of psu induced killing of M. smegmatis, M.
      bovis, X. campestris, and E. coli expressing S. enterica Rho indicating Psu
      induced inhibition of Rho proteins of these strains under physiological
      conditions. We propose that the "universal" inhibitory function of the Psu
      protein against the Rho proteins from both Gram-negative and Gram-positive
      bacteria could be useful for designing peptides with antimicrobial functions and
      that these peptides could contribute to synergistic antibiotic treatment of the
      pathogens by compromising the Rho functions.IMPORTANCE Bacteriophage-derived
      protein factors modulating different bacterial processes could be converted into
      unique antimicrobial agents. Bacteriophage P4 capsid protein Psu is an inhibitor
      of the E. coli transcription terminator Rho. Here we show that apart from
      antagonizing E. coli Rho, Psu is able to inhibit Rho proteins from various
      phylogenetically unrelated Gram-negative and Gram-positive pathogens. Upon
      binding to these Rho proteins, Psu inhibited them by affecting their ATPase and
      RNA release functions. The expression of Psu in vivo kills various pathogens,
      such as Mycobacterium and Xanthomonas species. Hence, Psu could be useful for
      identifying peptide sequences with anti-Rho activities and might constitute part
      of synergistic antibiotic treatment against pathogens.

PMID- 29038253
TI  - Conversion of Norepinephrine to 3,4-Dihdroxymandelic Acid in Escherichia coli
      Requires the QseBC Quorum-Sensing System and the FeaR Transcription Factor.
AB  - The detection of norepinephrine (NE) as a chemoattractant by Escherichia coli
      strain K-12 requires the combined action of the TynA monoamine oxidase and the
      FeaB aromatic aldehyde dehydrogenase. The role of these enzymes is to convert NE
      into 3,4-dihydroxymandelic acid (DHMA), which is a potent chemoattractant sensed
      by the Tsr chemoreceptor. These two enzymes must be induced by prior exposure to
      NE, and cells that are exposed to NE for the first time initially show minimal
      chemotaxis toward it. The induction of TynA and FeaB requires the QseC quorum
      sensing histidine kinase, and the signaling cascade requires new protein
      synthesis. Here, we demonstrate that the cognate response regulator for QseC, the
      transcription factor QseB, is also required for induction. The related quorum
      sensing kinase QseE appears not to be part of the signaling pathway, but its
      cognate response regulator, QseF, which is also a substrate for phosphotransfer
      from QseC, plays a nonessential role. The promoter of the feaR gene, which
      encodes a transcription factor that has been shown to be essential for the
      expression of tynA and feaB, has two predicted QseB-binding sites. One of these
      sites appears to be in an appropriate position to stimulate transcription from
      the P1 promoter of the feaR gene. This study unites two well-known pathways: one
      for expression of genes regulated by catecholamines (QseBC) and one for
      expression of genes required for metabolism of aromatic amines (FeaR, TynA, and
      FeaB). This cross talk allows E. coli to convert the host-derived and
      chemotactically inert NE into the potent bacterial chemoattractant
      DHMA.IMPORTANCE The chemotaxis of E. coli K-12 to norepinephrine (NE) requires
      the conversion of NE to 3,4-dihydroxymandleic acid (DHMA), and DHMA is both an
      attractant and inducer of virulence gene expression for a pathogenic
      enterohemorrhagic E. coli (EHEC) strain. The induction of virulence by DHMA and
      NE requires QseC. The results described here show that the cognate response
      regulator for QseC, QseB, is also required for conversion of NE into DHMA.
      Production of DHMA requires induction of a pathway involved in the metabolism of
      aromatic amines. Thus, the QseBC sensory system provides a direct link between
      virulence and chemotaxis, suggesting that chemotaxis to host signaling molecules
      may require that those molecules are first metabolized by bacterial enzymes to
      generate the actual chemoattractant.

PMID- 29038254
TI  - Characterization of Copy Number Control of Two Haloferax volcanii Replication
      Origins Using Deletion Mutants and Haloarchaeal Artificial Chromosomes.
AB  - Haloferax volcanii is polyploid and contains about 20 genome copies under optimal
      conditions. However, the chromosome copy number is highly regulated and ranges
      from two during phosphate starvation to more than 40 under conditions of
      phosphate surplus. The aim of this study was the characterization of the
      influence of two replication origins on the genome copy number. The origin
      repeats and the genes encoding origin recognition complex (ORC) proteins were
      deleted. The core origin oriC1-orc1 (ori1) deletion mutant had a lower genome
      copy number and a higher level of fitness than the wild type, in stark contrast
      to the oriC2-orc5 (ori2) deletion mutant. The genes adjacent to ori1 could not be
      deleted, and thus, at least two of them are probably essential, while deletion of
      the genes adjacent to ori2 was possible. Various fragments of and around the
      origins were cloned into a suicide plasmid to generate haloarchaeal artificial
      chromosomes (HACs). The copy number of the oriC1-orc1 HAC was much higher than
      that of the oriC2-orc5 HAC. The addition of adjacent genes influenced both the
      HAC copy number and the chromosome copy number. The results indicate that the
      origins of H. volcanii are not independent but that the copy number is regulated
      via a network of genes around the origins.IMPORTANCE Several species of archaea
      have more than one origin of replication on their major chromosome and are thus
      the only known prokaryotic species that allow the analysis of the evolution of
      multiorigin replication. The widely studied Haloferax volcanii H26 strain has a
      major chromosome with four origins of replication. Two origins, ori1 and ori2,
      were chosen for an in-depth analysis using deletion mutants and haloarchaeal
      artificial chromosomes. The analysis was not restricted to the core origin
      regions; origin-adjacent genes were also included. Because H. volcanii is
      polyploid, the effects on the chromosome copy number were of specific importance.
      The results revealed extreme differences between the two origins.

PMID- 29038256
TI  - Thiol Starvation induces redox-mediated dysregulation of Escherichia coli biofilm
      components.
AB  - A hallmark of bacterial biofilms is the production of an extracellular matrix
      (ECM) that encases and protects the community from environmental stressors.
      Biofilm formation is an integral portion of the uropathogenic Escherichia coli
      (UPEC) lifecycle. Approximately 2% of UPEC are cysteine auxotrophs. Here, we
      investigated how cysteine homeostasis impacted UPEC UTI89 strain biofilm
      formation and, specifically, the production of the ECM components curli and
      cellulose. Cysteine auxotrophs produced less cellulose and slightly more curli
      compared to wildtype (WT) strains, and cysteine auxotrophs formed smooth, non
      rugose colonies. Cellulose production was restored in cysteine auxotrophs when
      YfiR was inactivated. YfiR is a redox-sensitive regulator of the diguanylate
      cyclase, YfiN. Curli production, a temperature-regulated appendage, was
      independent of temperature in UTI89 cysteine auxotrophs. In a screen of UPEC
      isolates, we found that ~60% of UPEC cysteine auxotrophs produced curli at 37
      degrees C, but only ~2% of cysteine prototrophic UPEC produced curli at 37
      degrees C. Interestingly, sub-lethal concentrations of mecillinam and
      trimethoprim/sulfamethoxazole inhibited curli production, whereas strains
      auxotrophic for cysteine continued to produce curli even in the presence of
      mecillinam and trimethoprim/sulfamethoxazole. The dysregulation of ECM components
      and resistance to mecillinam in cysteine auxotrophs may be linked to hyper
      oxidation, since the addition of exogenous cysteine or glutathione restored WT
      biofilm phenotypes to strains unable to produce cysteine and
      glutathione.Importance Uropathogenic Escherichia coli (UPEC) are the predominant
      causative agent of urinary tract infections (UTIs). UTIs account for billions of
      dollars of financial burden to the healthcare industry in the United States
      annually. Biofilms are an important aspect of the UPEC pathogenesis cascade and
      for the establishment of chronic infections. Approximately 2% of UPEC strains
      isolated from UTIs are cysteine auxotrophs, yet there is relatively little known
      on the biofilm formation of UPEC cysteine auxotrophs. Here we show that cysteine
      auxotrophs have dysregulated biofilm components due to a change in the redox
      state of the periplasm. Additionally, we show the relationship between cysteine
      auxotrophs, biofilms, and antibiotics frequently used to treat UTIs.

PMID- 29038255
TI  - Studies of Pseudomonas aeruginosa Mutants Indicate Pyoverdine as the Central
      Factor in Inhibition of Aspergillus fumigatus Biofilm.
AB  - Pseudomonas aeruginosa and Aspergillus fumigatus are common opportunistic
      bacterial and fungal pathogens, respectively. They often coexist in airways of
      immunocompromised patients and individuals with cystic fibrosis, where they form
      biofilms and cause acute and chronic illnesses. Hence, the interactions between
      them have long been of interest and it is known that P. aeruginosa can inhibit A.
      fumigatusin vitro We have approached the definition of the inhibitory P.
      aeruginosa molecules by studying 24 P. aeruginosa mutants with various virulence
      genes deleted for the ability to inhibit A. fumigatus biofilms. The ability of P.
      aeruginosa cells or their extracellular products produced during planktonic or
      biofilm growth to affect A. fumigatus biofilm metabolism or planktonic A.
      fumigatus growth was studied in agar and liquid assays using conidia or hyphae.
      Four mutants, the pvdD pchE, pvdD, lasR rhlR, and lasR mutants, were shown to be
      defective in various assays. This suggested the P. aeruginosa siderophore
      pyoverdine as the key inhibitory molecule, although additional quorum sensing
      regulated factors likely contribute to the deficiency of the latter two mutants.
      Studies of pure pyoverdine substantiated these conclusions and included the
      restoration of inhibition by the pyoverdine deletion mutants. A correlation
      between the concentration of pyoverdine produced and antifungal activity was also
      observed in clinical P. aeruginosa isolates derived from lungs of cystic fibrosis
      patients. The key inhibitory mechanism of pyoverdine was chelation of iron and
      denial of iron to A. fumigatusIMPORTANCE Interactions between human pathogens
      found in the same body locale are of vast interest. These interactions could
      result in exacerbation or amelioration of diseases. The bacterium Pseudomonas
      aeruginosa affects the growth of the fungus Aspergillus fumigatus Both pathogens
      form biofilms that are resistant to therapeutic drugs and host immunity. P.
      aeruginosa and A. fumigatus biofilms are found in vivo, e.g., in the lungs of
      cystic fibrosis patients. Studying 24 P. aeruginosa mutants, we identified
      pyoverdine as the major anti-A. fumigatus compound produced by P. aeruginosa
      Pyoverdine captures iron from the environment, thus depriving A. fumigatus of a
      nutrient essential for its growth and metabolism. We show how microbes of
      different kingdoms compete for essential resources. Iron deprivation could be a
      therapeutic approach to the control of pathogen growth.

PMID- 29038257
TI  - The Novel Transcriptional Regulator LmbU Promotes Lincomycin Biosynthesis through
      Regulating Expression of Its Target Genes in Streptomyces lincolnensis.
AB  - Lincomycin A is a clinically important antimicrobial agent produced by
      Streptomyces lincolnensis In this study, a new regulator designated LmbU (GenBank
      accession no. ABX00623.1) was identified and characterized to regulate lincomycin
      biosynthesis in S. lincolnensis wild-type strain NRRL 2936. Both inactivation and
      overexpression of lmbU resulted in significant influences on lincomycin
      production. Transcriptional analysis and in vivo neomycin resistance (Neor)
      reporter assays demonstrated that LmbU activates expression of the lmbA, lmbC,
      lmbJ, and lmbW genes and represses expression of the lmbK and lmbU genes.
      Electrophoretic mobility shift assays (EMSAs) demonstrated that LmbU can bind to
      the regions upstream of the lmbA and lmbW genes through the consensus and
      palindromic sequence 5'-CGCCGGCG-3'. However, LmbU cannot bind to the regions
      upstream of the lmbC, lmbJ, lmbK, and lmbU genes as they lack this motif. These
      data indicate a complex transcriptional regulatory mechanism of LmbU. LmbU
      homologues are present in the biosynthetic gene clusters of secondary metabolites
      of many other actinomycetes. Furthermore, the LmbU homologue from
      Saccharopolyspora erythraea (GenBank accession no. WP_009944629.1) also binds to
      the regions upstream of lmbA and lmbW, which suggests widespread activity for
      this regulator. LmbU homologues have no significant structural similarities to
      other known cluster-situated regulators (CSRs), which indicates that they belong
      to a new family of regulatory proteins. In conclusion, the present report
      identifies LmbU as a novel transcriptional regulator and provides new insights
      into regulation of lincomycin biosynthesis in S. lincolnensisIMPORTANCE Although
      lincomycin biosynthesis has been extensively studied, its regulatory mechanism
      remains elusive. Here, a novel regulator, LmbU, which regulates transcription of
      its target genes in the lincomycin biosynthetic gene cluster (lmb gene cluster)
      and therefore promotes lincomycin biosynthesis, was identified in S. lincolnensis
      strain NRRL 2936. Importantly, we show that this new regulatory element is
      relatively widespread across diverse actinomycetes species. In addition, our
      findings provide a new strategy for improvement of yield of lincomycin through
      manipulation of LmbU, and this approach could also be evaluated in other
      secondary metabolite gene clusters containing this regulatory protein.

PMID- 29038258
TI  - A Single-Cell View of the BtsSR/YpdAB Pyruvate Sensing Network in Escherichia
      coli and Its Biological Relevance.
AB  - Fluctuating environments and individual physiological diversity force bacteria to
      constantly adapt and optimize the uptake of substrates. We focus here on two very
      similar two-component systems (TCSs) of Escherichia coli belonging to the
      LytS/LytTR family: BtsS/BtsR (formerly YehU/YehT) and YpdA/YpdB. Both TCSs
      respond to extracellular pyruvate, albeit with different affinities, typically
      during postexponential growth, and each system regulates expression of a single
      transporter gene, yjiY and yhjX, respectively. To obtain insights into the
      biological significance of these TCSs, we analyzed the activation of the target
      promoters at the single-cell level. We found unimodal cell-to-cell variability;
      however, the degree of variance was strongly influenced by the available
      nutrients and differed between the two TCSs. We hypothesized that activation of
      either of the TCSs helps individual cells to replenish carbon resources. To test
      this hypothesis, we compared wild-type cells with the btsSR ypdAB mutant under
      two metabolically modulated conditions: protein overproduction and persister
      formation. Although all wild-type cells were able to overproduce green
      fluorescent protein (GFP), about half of the btsSR ypdAB population was unable to
      overexpress GFP. Moreover, the percentage of persister cells, which tolerate
      antibiotic stress, was significantly lower in the wild-type cells than in the
      btsSR ypdAB population. Hence, we suggest that the BtsS/BtsR and YpdA/YpdB
      network contributes to a balancing of the physiological state of all cells within
      a population.IMPORTANCE Histidine kinase/response regulator (HK/RR) systems
      enable bacteria to respond to environmental and physiological fluctuations.
      Escherichia coli and other members of the Enterobacteriaceae possess two similar
      LytS/LytTR-type HK/RRs, BtsS/BtsR (formerly YehU/YehT) and YpdA/YpdB, which form
      a functional network. Both systems are activated in response to external
      pyruvate, typically when cells face overflow metabolism during post-exponential
      growth. Single-cell analysis of the activation of their respective target genes
      yjiY and yhjX revealed cell-to-cell variability, and the range of variation was
      strongly influenced by externally available nutrients. Based on the phenotypic
      characterization of a btsSR ypdAB mutant compared to the parental strain, we
      suggest that this TCS network supports an optimization of the physiological state
      of the individuals within the population.

PMID- 29038259
TI  - Novel Gene Encoding 5-Aminosalicylate 1,2-Dioxygenase from Comamonas sp. Strain
      QT12 and Catalytic Properties of the Purified Enzyme.
AB  - The 1,125-bp mabB gene encoding 5-aminosalicylate (5ASA) 1,2-dioxygenase, a
      nonheme iron dioxygenase in the bicupin family that catalyzes the cleavage of the
      5ASA aromatic ring to form cis-4-amino-6-carboxy-2-oxohexa-3,5-dienoate in the
      biodegradation of 3-aminobenzoate, was cloned from Comamonas sp. strain QT12 and
      characterized. The deduced amino acid sequence of the enzyme has low sequence
      identity with that of other reported ring-cleaving dioxygenases. MabB was
      heterologously expressed in Escherichia coli cells and purified as a His-tagged
      enzyme. The optimum pH and temperature for MabB are 8.0 and 10 degrees C,
      respectively. FeII is required for the catalytic activity of the purified enzyme.
      The apparent Km and Vmax values of MabB for 5ASA are 52.0 +/- 5.6 MUM and 850 +/-
      33.2 U/mg, respectively. The two oxygen atoms incorporated into the product of
      the MabB-catalyzed reaction are both from the dioxygen molecule. Both 5ASA and
      gentisate could be converted by MabB; however, the catalytic efficiency of MabB
      for 5ASA was much higher (~70-fold) than that for gentisate. The mabB-disrupted
      mutant lost the ability to grow on 3-aminobenzoate, and mabB expression was
      higher when strain QT12 was cultivated in the presence of 3-aminobenzoate. Thus,
      5ASA is the physiological substrate of MabB.IMPORTANCE For several decades, 5
      aminosalicylate (5ASA) has been advocated as the drug mesalazine to treat human
      inflammatory bowel disease and considered the key intermediate in the xenobiotic
      degradation of many aromatic organic pollutants. 5ASA biotransformation research
      will help us elucidate the microbial degradation of these pollutants. Most
      studies have reported that gentisate 1,2-dioxygenases (GDOs) can convert 5ASA
      with significantly high activity; however, the catalytic efficiency of these
      enzymes for gentisate is much higher than that for 5ASA. This study showed that
      MabB can convert 5ASA to cis-4-amino-6-carboxy-2-oxohexa-3,5-dienoate,
      incorporating two oxygen atoms from the dioxygen molecule into the product.
      Unlike GDOs, MabB uses 5ASA instead of gentisate as the primary substrate. mabB
      is the first reported 5-aminosalicylate 1,2-dioxygenase gene.

PMID- 29038260
TI  - Meropenem-Vaborbactam Resistance Selection, Resistance Prevention, and Molecular
      Mechanisms in Mutants of KPC-Producing Klebsiella pneumoniae.
AB  - Vaborbactam (formerly RPX7009) is a new beta-lactamase inhibitor based on a
      cyclic boronic acid pharmacophore with potent inhibitory activity against
      Klebsiella pneumoniaecarbapenemases (KPC). It has been developed in combination
      with meropenem. The objective of these studies was to identify the concentrations
      of both agents associated with the selection or prevention of single-step
      mutations leading to reduced sensitivity to the combination and to characterize
      the selected mutations. Eighteen strains of KPC-producing Klebsiella pneumoniae
      with various degrees of sensitivity to meropenem (MICs, 8 to 512 MUg/ml) and
      meropenem-vaborbactam (MICs, <=0.06 to 32 MUg/ml) and preexisting resistance
      mechanisms were selected from a worldwide collection of isolates recovered from
      surveillance studies, emphasizing strains for which MICs were in the upper range
      of the meropenem-vaborbactam MIC distribution. Meropenem and vaborbactam at 8
      MUg/ml each suppressed the drug resistance mutation frequency to <1 * 10-8 in
      77.8% (14/18) of strains, and all strains were inhibited when the meropenem
      concentration was increased to 16 MUg/ml. Mutants selected at lower drug
      concentrations showed phenotypes associated with previously described carbapenem
      resistance mechanisms, including ompK36 inactivation in mutants selected from
      OmpK36-proficient strains and an increased blaKPC gene copy number in strains
      with partially functional ompK36 No mutations in the coding region of blaKPC were
      identified. These data indicate that the selection of mutants with reduced
      sensitivity to meropenem-vaborbactam from KPC-producing Klebsiella pneumoniae
      strains is associated with previously described mechanisms involving porin
      mutations and the increase in the blaKPC gene copy number and not changes in the
      KPC enzyme and can be prevented by the drug concentrations achieved with optimal
      dosing of the combination.

PMID- 29038261
TI  - A Retrospective Cohort Analysis Shows that Coadministration of Minocycline with
      Colistin in Critically Ill Patients Is Associated with Reduced Frequency of Acute
      Renal Failure.
AB  - Nonclinical studies have suggested that oxidative damage, caspase-mediated
      apoptosis, and inducible nitric oxide synthase levels may be involved in the
      pathogenesis of colistin (CST)-associated acute renal failure. MIN inhibits
      caspase 1, caspase 3, and inducible nitric oxide synthase, leading to the
      hypothesis that coadministration of CST with MIN (CST-MIN) may reduce the
      incidence of acute renal failure as well as produce additive or synergistic
      antimicrobial effects. A multicenter retrospective cohort study was conducted
      using the Premier Research database to examine the impact of CST-MIN on acute
      renal failure. Inclusion criteria were as follows: age of >=18 years, intensive
      care unit admission at CST initiation, primary International Classification of
      Diseases 9 (ICD-9) diagnosis of pneumonia or sepsis, nondialysis at hospital
      admission, and discharge between January 2010 and December 2015. ICD-9 code
      584.XX or ICD-10 code N17 was used to define acute renal failure. Baseline
      comparisons, 1:8 propensity score matching, and confirmatory logistic regression
      analyses were conducted. In total, 4,817 patients received CST and met inclusion
      criteria; 93 received CST-MIN. Unadjusted frequency of acute renal failure was
      significantly lower in patients receiving CST-MIN than CST (11.8% versus 23.7%, P
      = 0.007). Similar results were seen in propensity score matching (12.0% versus
      22.3%, P = 0.031) and logistic regression analyses (odds ratio of 0.403, P =
      0.006). Mortalities and 30-day readmission rates were similar between groups. The
      acute renal failure rate was not impacted by prevalence of baseline renal
      disease. CST-MIN in critically ill patients may reduce CST-associated acute renal
      failure. Further evaluation of this combination in prospective clinical studies
      is warranted.

PMID- 29038262
TI  - Severe Infusion-Related Adverse Events and Renal Failure in Patients Receiving
      High-Dose Intravenous Polymyxin B.
AB  - The use of very high doses of polymyxin B (PMB) against carbapenem-resistant Gram
      negative bacilli has been addressed in in vitro experiments as a strategy to
      improve bacterial killing and suppress resistance emergence. However, the
      toxicities of very high doses in patients are unknown. We conducted a
      retrospective cohort study assessing patients receiving PMB at >3 mg/kg of body
      weight/day or a total dose of >=250 mg/day. The main outcomes were severe
      infusion-related adverse events according to the Common Terminology Criteria for
      Adverse Events and the renal failure category of RIFLE criteria for acute kidney
      injury (AKI) during treatment. A total of 222 patients were included for analysis
      of infusion-related events. The mean PMB dose was 3.61 +/- 0.97 mg/kg/day (median
      total dose/day = 268 mg). Severe infusion-related adverse events occurred in two
      patients, resulting in an incidence of 0.9% (95% confidence interval, 0.2 to
      3.2%); one was classified as a life-threatening adverse event, and one was
      classified as a severe adverse event. Renal failure was analyzed in 115 patients,
      and 25 (21.7%) patients presented renal failure (54 [47.0%] developed any degree
      of AKI, categorized as risk [27.8%], injury [25.9%], and failure [46.3%]).
      Treatment with a vasoactive drug, concomitant treatment with nephrotoxic drugs,
      and baseline creatinine clearance were independent risk factors for renal
      failure. Neither the PMB daily dose scaled by body weight nor the total daily
      dose was associated with renal failure. The in-hospital mortality rate was 60%
      (134 patients): 26% of deaths (57 patients) occurred during treatment, and none
      occurred during infusion. Our data suggest that high-dose schemes have an
      acceptable safety profile and could be further tested in clinical trials
      assessing strategies to improve patient outcomes and minimize the emergence of
      PMB resistance.

PMID- 29038263
TI  - In Vitro Combination of Isavuconazole with Echinocandins against Azole
      Susceptible and -Resistant Aspergillus spp.
AB  - In vitro combinations of isavuconazole with echinocandins were evaluated against
      30 Aspergillus strains with a two-dimensional checkerboard microdilution method
      and an agar-based diffusion method. With the checkerboard method, the three
      combinations showed indifferent interactions for all strains. With the agar-based
      method, indifferent interactions were found for all strains for isavuconazole
      micafungin and isavuconazole-anidulafungin. For the isavuconazole-caspofungin
      combination, indifference was found in 24/30 strains, synergism in 4/30 strains,
      and antagonism in 2/30 strains.

PMID- 29038264
TI  - Clinical Evolution of New Delhi Metallo-beta-Lactamase (NDM) Optimizes Resistance
      under Zn(II) Deprivation.
AB  - Carbapenem-resistant Enterobacteriaceae (CRE) are rapidly spreading and taking a
      staggering toll on all health care systems, largely due to the dissemination of
      genes coding for potent carbapenemases. An important family of carbapenemases are
      the Zn(II)-dependent beta-lactamases, known as metallo-beta-lactamases (MBLs).
      Among them, the New Delhi metallo-beta-lactamase (NDM) has experienced the
      fastest and widest geographical spread. While other clinically important MBLs are
      soluble periplasmic enzymes, NDMs are lipoproteins anchored to the outer membrane
      in Gram-negative bacteria. This unique cellular localization endows NDMs with
      enhanced stability upon the Zn(II) starvation elicited by the immune system
      response at the sites of infection. Since the first report of NDM-1, new allelic
      variants (16 in total) have been identified in clinical isolates differing by a
      limited number of substitutions. Here, we show that these variants have evolved
      by accumulating mutations that enhance their stability or the Zn(II) binding
      affinity in vivo, overriding the most common evolutionary pressure acting on
      catalytic efficiency. We identified the ubiquitous substitution M154L as
      responsible for improving the Zn(II) binding capabilities of the NDM variants.
      These results also reveal that Zn(II) deprivation imposes a strict constraint on
      the evolution of this MBL, overriding the most common pressures acting on
      catalytic performance, and shed light on possible inhibitory strategies.

PMID- 29038265
TI  - Verapamil Increases the Bioavailability and Efficacy of Bedaquiline but Not
      Clofazimine in a Murine Model of Tuberculosis.
AB  - Drug efflux pumps play important roles in intrinsic and acquired drug resistance.
      Verapamil, an efflux inhibitor that enhances the activity of bedaquiline,
      clofazimine, and other drugs against Mycobacterium tuberculosis, has been
      proposed as a potential adjunctive agent for treatment of tuberculosis (TB).
      However, the extent to which verapamil enhances in vivo efficacy by inhibiting
      bacterial efflux pumps versus inhibiting mammalian drug transporters to improve
      oral bioavailability has not been delineated. We found that verapamil potentiated
      the in vitro activity of bedaquiline and clofazimine against M. tuberculosis
      clinical isolates, including those harboring rv0678 mutations. Verapamil
      increased the efficacy of bedaquiline in a murine TB model by the same extent to
      which it increased systemic bedaquiline exposure. However, verapamil showed no
      effect on the oral bioavailability or efficacy of clofazimine in mice. The
      addition of verapamil increased the sterilizing activity of a regimen composed of
      bedaquiline, clofazimine, and pyrazinamide. These results confirm that verapamil
      has adjunctive activity in vivo, but they also demonstrate that the adjunctive
      effect is likely due to enhanced systemic exposure to companion drugs via effects
      on mammalian transporters, rather than inhibition of bacterial pumps. Therefore,
      there may be no advantage to administering verapamil versus increasing the doses
      of companion drugs.

PMID- 29038266
TI  - Potency of Meropenem-Vaborbactam in Lung Surfactant.
AB  - This study investigated whether pulmonary surfactant has an effect on the in
      vitro antibacterial activity of either meropenem alone or meropenem in
      combination with vaborbactam at a fixed concentration of 8 MUg/ml against several
      Klebsiella pneumoniae carbapenemase (KPC)-producing strains of Gram-negative
      bacteria. Results showed that the potency of meropenem alone and that of
      meropenem-vaborbactam were not affected when tested with pulmonary surfactant.

PMID- 29038267
TI  - A Retrospective Analysis of Treatment and Clinical Outcomes among Patients with
      Methicillin-Susceptible Staphylococcus aureus Bloodstream Isolates Possessing
      Detectable mecA by a Commercial PCR Assay Compared to Patients with Methicillin
      Resistant Staphylococcus aureus Bloodstream Isolates.
AB  - mecA-positive Staphylococcus aureus isolates phenotypically susceptible to
      cefoxitin (mecA-methicillin-sensitive S. aureus [MSSA]) have been identified. We
      describe the treatment and outcomes among patients with mecA-MSSA bloodstream
      infections (BSI) and MRSA BSI matched 1:1 for age, BSI origin, and BSI type (n =
      17 per group). Compared to MRSA BSI patients, mecA-MSSA BSI patients more often
      experienced clinical failure (58.8% and 11.8%, P = 0.010), driven largely by
      persistent bacteremia (35.3% and 11.8%). mecA-MSSA BSI patients may be at higher
      risk for poor clinical outcomes.

PMID- 29038268
TI  - Urinary Tract Conditions Affect Fosfomycin Activity against Escherichia coli
      Strains Harboring Chromosomal Mutations Involved in Fosfomycin Uptake.
AB  - The steps by which Escherichia coli strains harboring mutations related to
      fosfomycin (FOS) resistance arise and spread during urinary tract infections
      (UTIs) are far from being understood. The aim of this study was to evaluate the
      effects of urine, pH, and anaerobiosis on FOS activity against a set of isogenic
      strains carrying the most prevalent chromosomal mutations conferring FOS
      resistance (DeltauhpT, DeltaglpT, DeltacyaA, and DeltaptsI), either singly or in
      combination. We also studied fosfomycin-resistant E. coli clinical isolates from
      patients with UTI. Our results demonstrate that urinary tract physiological
      conditions might have a profound impact on FOS activity against strains with
      chromosomal FOS resistance mutations. Specifically, acidic pH values and
      anaerobiosis convert most of the strains categorized as resistant to fosfomycin
      according to the international guidelines to a susceptible status. Therefore,
      urinary pH values may have practical interest in the management of UTIs. Finally,
      our results, together with the high fitness cost associated with FOS resistance
      mutations, might explain the low prevalence of fosfomycin-resistant E. coli
      variants in UTIs.

PMID- 29038270
TI  - Activity of Meropenem-Vaborbactam against Carbapenem-Resistant Enterobacteriaceae
      in a Murine Model of Pyelonephritis.
AB  - The recently approved combination of meropenem and vaborbactam (Vabomere) is
      highly active against Gram-negative pathogens, especially Klebsiella pneumoniae
      carbapenemase (KPC)-producing, carbapenem-resistant Enterobacteriaceae We
      evaluated the efficacy of meropenem-vaborbactam against three clinically relevant
      isolates in a murine pyelonephritis model. The data indicate that the combination
      of meropenem and vaborbactam significantly increased bacterial killing compared
      to that with the untreated controls. These data suggest that this combination may
      have utility in the treatment of complicated urinary tract infections due to KPC
      producing, carbapenem-resistant Enterobacteriaceae.

PMID- 29038269
TI  - A Systematic Review and Meta-analyses of the Clinical Epidemiology of Carbapenem
      Resistant Enterobacteriaceae.
AB  - Carbapenem-resistant Enterobacteriaceae (CRE) are major health care-associated
      pathogens and responsible for hospital outbreaks worldwide. To prevent a further
      increase in CRE infections and to improve infection prevention strategies, it is
      important to summarize the current knowledge about CRE infection prevention in
      hospital settings. This systematic review aimed to identify risk factors for CRE
      acquisition among hospitalized patients. In addition, we summarized the
      environmental sources/reservoirs and the most successful infection prevention
      strategies related to CRE. A total of 3,983 potentially relevant articles were
      identified and screened. Finally, we included 162 studies in the systematic
      review, of which 69 studies regarding risk factors for CRE acquisition were
      included in the random-effects meta-analysis studies. The meta-analyses regarding
      risk factors for CRE acquisition showed that the use of medical devices generated
      the highest pooled estimate (odds ratio [OR] = 5.09; 95% confidence interval [CI]
      = 3.38 to 7.67), followed by carbapenem use (OR = 4.71; 95% CI = 3.54 to 6.26).
      To control hospital outbreaks, bundled interventions, including the use of
      barrier/contact precautions for patients colonized or infected with CRE, are
      needed. In addition, it is necessary to optimize the therapeutic approach, which
      is an important message to infectious disease specialists, who need to be
      actively involved in a timely manner in the treatment of patients with known CRE
      infections or suspected carriers of CRE.

PMID- 29038271
TI  - Evaluation of Antifungal Efficacy of Three New Cyclic Lipopeptides of the Class
      Bacillomycin from Bacillus subtilis RLID 12.1.
AB  - New lipopeptide homologues (AF3, AF4, and AF5) with antifungal activities against
      Candida and Cryptococcus spp. were purified from a cell-free supernatant of
      Bacillus subtilis RLID 12.1. The lipopeptides AF3, AF4, and AF5 were identified
      with the same peptide sequence Asn-Pro-Tyr-Asn-Gln-Thr-Ser with variations in the
      fatty acid branching type and chain length (anteiso-C17, iso-C17, and iso-C18,
      respectively). Upon comparing the three homologues for MICs against 81 Candida (n
      = 64) and Cryptococcus (n = 17) clinical isolates and their cytotoxicities, we
      found that AF4 was the most promising antifungal lipopeptide, since it
      demonstrated 100% inhibition at geometric mean MICs of 3.31, 3.41, 3.48, and 2.83
      MUg/ml against Candida albicans, Candida tropicalis, Candida auris, and
      Cryptococcus neoformans, respectively, with low hemolysis values (<6%) and 50%
      inhibitory concentrations (13.31 MUg/ml). The additive effects among the
      homologues AF3, AF4, and AF5 were evaluated against three Candida species, along
      with the cytotoxicity studies. Five combinations exhibited good additive
      interaction effects: AF3/AF4 (at corresponding concentrations of 4 and 4 MUg/ml
      [4/4 MUg/ml]), AF3/AF5 (4/4 MUg/ml), AF3/AF5 (2/4 MUg/ml), AF4/AF5 (4/4 MUg/ml),
      and AF4/AF5 (2/4 MUg/ml) in planktonic cell inhibition and AF3/AF4 (4/4 MUg/ml),
      AF3/AF5 (4/4 MUg/ml), and AF3/AF5 (2/4 MUg/ml) in the inhibition of biofilm
      formation. However, combinations AF3/AF4 and AF3/AF5, which showed >70% cell
      survival with low hemolysis (<5%), were found to be comparatively effective. We
      describe here the additive effects of lipopeptide homologues showing reduced
      cytotoxicity against mammalian cells; these combinations might serve as a potent
      antibiofilm-forming substitute.

PMID- 29038272
TI  - Population Pharmacokinetic Analysis of Cefiderocol, a Parenteral Siderophore
      Cephalosporin, in Healthy Subjects, Subjects with Various Degrees of Renal
      Function, and Patients with Complicated Urinary Tract Infection or Acute
      Uncomplicated Pyelonephritis.
AB  - Cefiderocol, a novel parenteral siderophore cephalosporin, exhibits potent
      efficacy against most Gram-negative bacteria, including carbapenem-resistant
      strains. The aim of this study was to perform a population pharmacokinetic (PK)
      analysis based on plasma cefiderocol concentrations in healthy subjects, subjects
      with various degrees of renal function, and patients with complicated urinary
      tract infection (cUTI) or acute uncomplicated pyelonephritis (AUP) caused by Gram
      negative pathogens and to calculate the fraction of the time during the dosing
      interval where the free drug concentration in plasma exceeds the MIC (fTMIC).
      Population PK models were developed with three renal function markers, body
      surface area-adjusted estimated glomerular filtration rate (eGFR), absolute eGFR,
      and creatinine clearance, on the basis of 2,571 plasma concentrations from 91
      subjects without infection and 238 patients with infection. The population PK
      models with each renal function marker adequately described the plasma
      cefiderocol concentrations. Clear relationships of total clearance (CL) to all
      renal function markers were observed. Body weight and disease status (with or
      without infection) were also significant covariates. The CL in patients with
      infection was 26% higher than that in subjects without infection. The fTMIC
      values were more than 75% in all patients (and were 100% in most patients),
      suggesting that a sufficient exposure to cefiderocol was provided by the tested
      dose regimens (2 g every 8 h as the standard dose regimen) for the treatment of
      cUTI or AUP caused by Gram-negative pathogens.

PMID- 29038273
TI  - Pharmacokinetic Modeling of Voriconazole To Develop an Alternative Dosing Regimen
      in Children.
AB  - The pharmacokinetic variability of voriconazole (VCZ) in immunocompromised
      children is high, and adequate exposure, particularly in the first days of
      therapy, is uncertain. A population pharmacokinetic model was developed to
      explore VCZ exposure in plasma after alternative dosing regimens. Concentration
      data were obtained from a pediatric phase II study. Nonlinear mixed effects
      modeling was used to develop the model. Monte Carlo simulations were performed to
      test an array of three-times-daily (TID) intravenous dosing regimens in children
      2 to 12 years of age. A two-compartment model with first-order absorption,
      nonlinear Michaelis-Menten elimination, and allometric scaling best described the
      data (maximal kinetic velocity for nonlinear Michaelis-Menten clearance [Vmax] =
      51.5 mg/h/70 kg, central volume of distribution [V1] = 228 liters/70 kg,
      intercompartmental clearance [Q] = 21.9 liters/h/70 kg, peripheral volume of
      distribution [V2] = 1,430 liters/70 kg, bioavailability [F] = 59.4%, Km = fixed
      value of 1.15 mg/liter, absorption rate constant = fixed value of 1.19 h-1).
      Interindividual variabilities for Vmax, V1, Q, and F were 63.6%, 45.4%, 67%, and
      1.34% on a logit scale, respectively, and residual variability was 37.8%
      (proportional error) and 0.0049 mg/liter (additive error). Monte Carlo
      simulations of a regimen of 9 mg/kg of body weight TID simulated for 24, 48, and
      72 h followed by 8 mg/kg two times daily (BID) resulted in improved early target
      attainment relative to that with the currently recommended BID dosing regimen but
      no increased rate of accumulation thereafter. Pharmacokinetic modeling suggests
      that intravenous TID dosing at 9 mg/kg per dose for up to 3 days may result in a
      substantially higher percentage of children 2 to 12 years of age with adequate
      exposure to VCZ early during treatment. Before implementation of this regimen in
      patients, however, validation of exposure, safety, and tolerability in a
      carefully designed clinical trial would be needed.

PMID- 29038274
TI  - Thrombocytopenia with Tedizolid and Linezolid.
AB  - Several studies have suggested the risk of thrombocytopenia with tedizolid, a
      second-in-class oxazolidinone antibiotic (approved June 2014), is less than that
      observed with linezolid (first-in-class oxazolidinone). Using data from the Food
      and Drug Administration adverse event reporting system (July 2014 through
      December 2016), we observed significantly increased risks of thrombocytopenia of
      similar magnitudes with both antibiotics: linezolid reporting odds ratio [ROR],
      37.9 (95% confidence interval [CI], 20.78 to 69.17); tedizolid ROR, 34.0 (95% CI,
      4.67 to 247.30).

PMID- 29038275
TI  - In Vivo Bioluminescent Monitoring of Therapeutic Efficacy and Pharmacodynamic
      Target Assessment of Antofloxacin against Escherichia coli in a Neutropenic
      Murine Thigh Infection Model.
AB  - Antimicrobial resistance among uropathogens has increased the rates of infection
      related morbidity and mortality. Antofloxacin is a novel fluoroquinolone with
      broad-spectrum antibacterial activity against urinary Gram-negative bacilli, such
      as Escherichia coli This study monitored the in vivo efficacy of antofloxacin
      using bioluminescent imaging and determined pharmacokinetic (PK)/pharmacodynamic
      (PD) targets against E. coli isolates in a neutropenic murine thigh infection
      model. The PK properties were determined after subcutaneous administration of
      antofloxacin at 2.5, 10, 40, and 160 mg/kg of body weight. Following thigh
      infection, the mice were treated with 2-fold-increasing doses of antofloxacin
      from 2.5 to 80 mg/kg administered every 12 h. Efficacy was assessed by
      quantitative determination of the bacterial burdens in thigh homogenates and was
      compared with the bioluminescent density. Antofloxacin demonstrated both static
      and killing endpoints in relation to the initial burden against all study
      strains. The PK/PD index area under the concentration-time curve (AUC)/MIC
      correlated well with efficacy (R2 = 0.92), and the dose-response relationship was
      relatively steep, as observed with escalating doses of antofloxacin. The mean
      free drug AUC/MIC targets necessary to produce net bacterial stasis and 1-log10
      and 2-log10 kill for each isolate were 38.7, 66.1, and 147.0 h, respectively. In
      vivo bioluminescent imaging showed a rapid decrease in the bioluminescent density
      at free drug AUC/MIC exposures that exceeded the stasis targets. The integration
      of these PD targets combined with the results of PK studies with humans will be
      useful in setting optimal dosing regimens for the treatment of urinary tract
      infections due to E. coli.

PMID- 29038276
TI  - Reduced Chlorhexidine and Daptomycin Susceptibility in Vancomycin-Resistant
      Enterococcus faecium after Serial Chlorhexidine Exposure.
AB  - Vancomycin-resistant Enterococcus faecium strains (VREfm) are critical public
      health concerns because they are among the leading causes of hospital-acquired
      bloodstream infections. Chlorhexidine (CHX) is a bisbiguanide cationic antiseptic
      that is routinely used for patient bathing and other infection control practices.
      VREfm are likely frequently exposed to CHX; however, the long-term effects of CHX
      exposure have not been studied in enterococci. In this study, we serially exposed
      VREfm to increasing concentrations of CHX for a period of 21 days in two
      independent experimental evolution trials. Reduced CHX susceptibility emerged (4
      fold shift in CHX MIC). Subpopulations with reduced daptomycin (DAP)
      susceptibility were detected, which were further analyzed by genome sequencing
      and lipidomic analysis. Across the trials, we identified adaptive changes in
      genes with predicted or experimentally confirmed roles in chlorhexidine
      susceptibility (efrE), global nutritional stress response (relA), nucleotide
      metabolism (cmk), phosphate acquisition (phoU), and glycolipid biosynthesis
      (bgsB), among others. Moreover, significant alterations in membrane phospholipids
      were identified for some populations with reduced DAP susceptibility. Our results
      are clinically significant because they identify a link between serial
      subinhibitory CHX exposure and reduced DAP susceptibility. In addition, the CHX
      induced genetic and lipidomic changes described in this study offer new insights
      into the mechanisms underlying the emergence of antibiotic resistance in VREfm.

PMID- 29038277
TI  - Dilution Factor of Quantitative Bacterial Cultures Obtained by Bronchoalveolar
      Lavage in Patients with Ventilator-Associated Bacterial Pneumonia.
AB  - Ventilator-associated bacterial pneumonia (VABP) is a difficult therapeutic
      problem. Considerable controversy exists regarding the optimal chemotherapy for
      this entity. The recent guidelines of the Infectious Diseases Society of America
      and the American Thoracic Society recommend a 7-day therapeutic course for VABP
      based on the balance of no negative impact on all-cause mortality, less
      resistance emergence, and fewer antibiotic treatment days, counterbalanced with a
      higher relapse rate for patients whose pathogen is a nonfermenter. The bacterial
      burden causing an infection has a substantial impact on treatment outcome and
      resistance selection. We describe the baseline bronchoalveolar lavage (BAL) fluid
      burden of organisms in suspected VABP patients screened for inclusion in a
      clinical trial. We measured the urea concentrations in plasma and BAL fluid to
      provide an index of the dilution of the bacterial and drug concentrations in the
      lung epithelial lining fluid introduced by the BAL procedure. We were then able
      to calculate the true bacterial burden as the diluted colony count times the
      dilution factor. The median dilution factor was 28.7, with the interquartile
      range (IQR) being 11.9 to 53.2. Median dilution factor-corrected colony counts
      were 6.18 log10(CFU/ml) [IQR, 5.43 to 6.46 log10(CFU/ml)]. In a subset of
      patients, repeat BAL on day 5 showed a good stability of the dilution factor. We
      previously showed that large bacterial burdens reduce or stop bacterial killing
      by granulocytes. (This study has been registered at ClinicalTrials.gov under
      registration no. NCT01570192.).

PMID- 29038278
TI  - Fidaxomicin and OP-1118 Inhibit Clostridium difficile Toxin A- and B-Mediated
      Inflammatory Responses via Inhibition of NF-kappaB Activity.
AB  - Clostridium difficile causes diarrhea and colitis by releasing toxin A and toxin
      B. In the human colon, both toxins cause intestinal inflammation and stimulate
      tumor necrosis factor alpha (TNF-alpha) expression via the activation of NF
      kappaB. It is well established that the macrolide antibiotic fidaxomicin is
      associated with reduced relapses of C. difficile infection. We showed that
      fidaxomicin and its primary metabolite OP-1118 significantly inhibited toxin A
      mediated intestinal inflammation in mice in vivo and toxin A-induced cell
      rounding in vitro We aim to determine whether fidaxomicin and OP-1118 possess
      anti-inflammatory effects against toxin A and toxin B in the human colon and
      examine the mechanism of this response. We used fresh human colonic explants,
      NCM460 human colonic epithelial cells, and RAW264.7 mouse macrophages to study
      the mechanism of the activity of fidaxomicin and OP-1118 against toxin A- and B
      mediated cytokine expression and apoptosis. Fidaxomicin and OP-1118 dose
      dependently inhibited toxin A- and B-induced TNF-alpha and interleukin-1beta (IL
      1beta) mRNA expression and histological damage in human colonic explants.
      Fidaxomicin and OP-1118 inhibited toxin A-mediated NF-kappaB phosphorylation in
      human and mouse intestinal mucosae. Fidaxomicin and OP-1118 also inhibited toxin
      A-mediated NF-kappaB phosphorylation and TNF-alpha expression in macrophages,
      which was reversed by the NF-kappaB activator phorbol myristate acetate (PMA).
      Fidaxomicin and OP-1118 prevented toxin A- and B-mediated apoptosis in NCM460
      cells, which was reversed by the addition of PMA. PMA reversed the cytoprotective
      effect of fidaxomicin and OP-1118 in toxin-exposed human colonic explants.
      Fidaxomicin and OP-1118 inhibit C. difficile toxin A- and B-mediated inflammatory
      responses, NF-kappaB phosphorylation, and tissue damage in the human colon.

PMID- 29038279
TI  - A CTG Clade Candida Yeast Genetically Engineered for the Genotype-Phenotype
      Characterization of Azole Antifungal Resistance in Human-Pathogenic Yeasts.
AB  - A strain of the opportunistic pathogenic yeast Candida lusitaniae was genetically
      modified for use as a cellular model for assessing by allele replacement the
      impact of lanosterol C14alpha-demethylase ERG11 mutations on azole resistance.
      Candida lusitaniae was chosen because it is susceptible to azole antifungals, it
      belongs to the CTG clade of yeast, which includes most of the Candida species
      pathogenic for humans, and it is haploid and easily amenable to genetic
      transformation and molecular modeling. In this work, allelic replacement is
      targeted at the ERG11 locus by the reconstitution of a functional auxotrophic
      marker in the 3' intergenic region of ERG11 Homologous and heterologous ERG11
      alleles are expressed from the resident ERG11 promoter of C. lusitaniae, allowing
      accurate comparison of the phenotypic change in azole susceptibility. As a proof
      of concept, we successfully expressed in C. lusitaniae different ERG11 alleles,
      either bearing or not bearing mutations retrieved from a clinical context, from
      two phylogenetically distant yeasts, C. albicans and Kluyveromyces
      marxianusCandida lusitaniae constitutes a high-fidelity expression system, giving
      specific Erg11p-dependent fluconazole MICs very close to those observed with the
      ERG11 donor strain. This work led us to characterize the phenotypic effect of two
      kinds of mutation: mutation conferring decreased fluconazole susceptibility in a
      species-specific manner and mutation conferring fluconazole resistance in several
      yeast species. In particular, a missense mutation affecting amino acid K143 of
      Erg11p in Candida species, and the equivalent position K151 in K. marxianus,
      plays a critical role in fluconazole resistance.

PMID- 29038280
TI  - Targeting Human-Cytomegalovirus-Infected Cells by Redirecting T Cells Using an
      Anti-CD3/Anti-Glycoprotein B Bispecific Antibody.
AB  - The host immune response to human cytomegalovirus (HCMV) is effective against
      HCMV reactivation from latency, though not sufficient to clear the virus. T cells
      are primarily responsible for the control of viral reactivation. When the host
      immune system is compromised, as in transplant recipients with immunosuppression,
      HCMV reactivation and progressive infection can cause serious morbidity and
      mortality. Adoptive T cell therapy is effective for the control of HCMV infection
      in transplant recipients. However, it is a highly personalized therapeutic
      regimen and is difficult to implement in routine clinical practice. In this
      study, we explored a bispecific-antibody strategy to direct non-HCMV-specific T
      cells to recognize and exert effector functions against HCMV-infected cells.
      Using a knobs-into-holes strategy, we constructed a bispecific antibody in which
      one arm is specific for CD3 and can trigger T cell activation, while the other
      arm, specific for HCMV glycoprotein B (gB), recognizes and marks HCMV-infected
      cells based on the expression of viral gB on their surfaces. We showed that this
      bispecific antibody was able to redirect T cells with specificity for HCMV
      infected cells in vitro In the presence of HCMV infection, the engineered
      antibody was able to activate T cells with no HCMV specificity for cytokine
      production, proliferation, and the expression of phenotype markers unique to T
      cell activation. These results suggested the potential of engineered bispecific
      antibodies, such as the construct described here, as prophylactic or therapeutic
      agents against HCMV reactivation and infection.

PMID- 29038281
TI  - Putative Integrative Mobile Elements That Exploit the Xer Recombination Machinery
      Carrying blaIMI-Type Carbapenemase Genes in Enterobacter cloacae Complex Isolates
      in Singapore.
AB  - Whole-genome sequencing was performed on 16 isolates of the carbapenemase
      producing Enterobacter cloacae complex to determine the flanking regions of
      blaIMI-type genes. Phylogenetic analysis of multilocus sequence typing (MLST)
      targets separated the isolates into 4 clusters. The blaIMI-type genes were all
      found on Xer-dependent integrative mobile elements (IMEX). The IMEX elements of 5
      isolates were similar to those described in Canada, while the remainder were
      novel. Five isolates had IMEX elements lacking a resolvase and recombinase.

PMID- 29038282
TI  - Intracellular Tenofovir-Diphosphate and Emtricitabine-Triphosphate in Dried Blood
      Spots following Directly Observed Therapy.
AB  - Studies of daily emtricitabine-tenofovir disoproxil fumarate (FTC-TDF) for HIV
      preexposure prophylaxis (PrEP) in men who have sex with men (MSM) modeled
      intracellular tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) to assess
      adherence and corresponding PrEP outcomes. We conducted a prospective,
      randomized, crossover pharmacokinetic study of TFV-DP in DBS during 33%, 67%, or
      100% of daily dosing under directly observed therapy (DOT). Participants were
      assigned to two 12-week dosing regimens, separated by a 12-week washout. Forty
      eight adults (25 women) from Denver and San Francisco were included. TFV-DP
      exhibited a median half-life of 17 days, reaching steady state in 8 weeks. TFV-DP
      was dose proportional with mean (SD) steady-state concentrations of 530 (159),
      997 (267), and 1,605 (405) fmol/punch for the 33%, 67%, and 100% arms,
      respectively. Prior work in MSM demonstrated clinically meaningful TFV-DP
      thresholds of 350, 700, and 1,250 fmol/punch, which were estimated 25th
      percentiles for 2, 4, and 7 doses/week. In the present study, corresponding TFV
      DP was within 3% of the prior estimates, and subgroups by site, race, and sex
      were within 14% of prior estimates, although males had 17.6% (95% confidence
      intervals [CIs], 6.5, 27.4%) lower TFV-DP than females. The thresholds of 350,
      700, and 1,250 fmol/punch were achieved by 75% of men taking >=1.2, 3.2, and 6
      doses/week and 75% of women taking >=0.6, 2.0, and 5.3 doses/week, indicating
      that lower dosing reached these thresholds for both sexes. In conclusion, TFV-DP
      arising from DOT was similar to previous estimates and is useful for interpreting
      PrEP adherence and study outcomes. (This study has been registered at
      ClinicalTrials.gov under identifier NCT02022657.).

PMID- 29038283
TI  - CTX-M-15-Producing Shewanella Species Clinical Isolate Expressing OXA-535, a
      Chromosome-Encoded OXA-48 Variant, Putative Progenitor of the Plasmid-Encoded OXA
      436.
AB  - Shewanella spp. constitute a reservoir of antibiotic resistance determinants. In
      a bile sample, we identified three extended-spectrum-beta-lactamase (ESBL)
      producing bacteria (Escherichia coli, Klebsiella pneumoniae, and Shewanella sp.
      strain JAB-1) isolated from a child suffering from cholangitis. Our objectives
      were to characterize the genome and the resistome of the first ESBL-producing
      isolate of the genus Shewanella and determine whether plasmidic exchange occurred
      between the three bacterial species. Bacterial isolates were characterized using
      matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS), standard biochemical tools, and antimicrobial susceptibility
      testing. Shewanella sp. JAB-1 and ESBL gene-encoding plasmids were characterized
      using PacBio and Illumina whole-genome sequencing, respectively. The Shewanella
      sp. JAB-1 chromosome-encoded OXA-48 variant was cloned and functionally
      characterized. Whole-genome sequencing (WGS) of the Shewanella sp. clinical
      isolate JAB-1 revealed the presence of a 193-kb plasmid belonging to the IncA/C
      incompatibility group and harboring two ESBL genes, blaCTX-M-15 and blaSHV
      2ablaCTX-M-15 gene-carrying plasmids belonging to the IncY and IncR
      incompatibility groups were also found in the E. coli and K. pneumoniae isolates
      from the same patient, respectively. A comparison of the blaCTX-M-15 genetic
      environment indicated the independent origin of these plasmids and dismissed in
      vivo transfers. Furthermore, characterization of the resistome of Shewanella sp.
      JAB-1 revealed the presence of a chromosome-carried blaOXA-535 gene, likely the
      progenitor of the plasmid-carried blaOXA-436 gene, a novel blaOXA-48-like gene.
      The expression of blaOXA-535 in E. coli showed the carbapenem-hydrolyzing
      activity of OXA-535. The production of OXA-535 in Shewanella sp. JAB-1 could be
      evidenced using molecular and immunoenzymatic tests, but not with biochemical
      tests that monitor carbapenem hydrolysis. In this study, we have identified a CTX
      M-15-producing Shewanella species that was responsible for a hepatobiliary
      infection and that is likely the progenitor of OXA-436, a novel plasmid-encoded
      OXA-48-like class D carbapenemase.

PMID- 29038284
TI  - Evaluation of the Microbiological Efficacy of a Single 2-Gram Dose of Extended
      Release Azithromycin by Population Pharmacokinetics and Simulation in Japanese
      Patients with Gonococcal Urethritis.
AB  - The objective of this study was to analyze the relationship between the
      pharmacokinetic (PK)/pharmacodynamic (PD) parameters of a single 2-g dose of
      extended-release formulation of azithromycin (AZM-SR) and its microbiological
      efficacy against gonococcal urethritis. Fifty male patients with gonococcal
      urethritis were enrolled in this study. In 36 patients, the plasma AZM
      concentrations were measured using liquid chromatography-tandem mass
      spectrometry, the AZM MIC values for the Neisseria gonorrhoeae isolates were
      determined, and the microbiological outcomes were assessed. AZM-SR monotherapy
      eradicated N. gonorrhoeae in 30 (83%) of the 36 patients. AZM MICs ranged from
      0.03 to 2 mg/liter. The mean value of the area under the concentration-time curve
      (AUC), estimated by population PK analysis using a two-compartment model, was
      20.8 mg . h/liter. Logistic regression analysis showed that the PK/PD target
      value required to predict an N. gonorrhoeae eradication rate of >=95% was a
      calculated AUC/MIC of >=59.5. The AUC/MIC value was significantly higher in
      patients who achieved microbiological cure than in patients who achieved
      microbiological failure. Monte Carlo simulation using this MIC distribution
      revealed that the probability that AZM-SR monotherapy would produce an AUC/MIC
      exceeding the AUC/MIC target of 59.5 was 47%. Furthermore, the MIC distribution
      for strains isolated in this study was mostly consistent with that for strains
      currently circulating in Japan. In conclusion, in Japan, AZM-SR monotherapy may
      not be effective against gonococcal urethritis. Therefore, use of a single 2-g
      dose of AZM-SR either with or without other antibiotics could be an option to
      treat gonococcal urethritis if patients are allergic to ceftriaxone and
      spectinomycin or are diagnosed to be infected with an AZM-sensitive strain.

PMID- 29038285
TI  - Metabolic Effects of Diet and Exercise in Patients with Moderate to Severe CKD: A
      Randomized Clinical Trial.
AB  - CKD is steadily increasing along with obesity worldwide. Furthermore, obesity is
      a proinflammatory risk factor for progression of CKD and cardiovascular disease.
      We tested the hypothesis that implementation of caloric restriction and aerobic
      exercise is feasible and can improve the proinflammatory metabolic milieu in
      patients with moderate to severe CKD through a pilot, randomized, 2*2 factorial
      design trial. Of 122 participants consented, 111 were randomized to receive
      caloric restriction and aerobic exercise, caloric restriction alone, aerobic
      exercise alone, or usual care. Of those randomized, 42% were women, 25% were
      diabetic, and 91% were hypertensive; 104 started intervention, and 92 completed
      the 4-month study. Primary outcomes were a change from baseline in absolute fat
      mass, body weight, plasma F2-isoprostane concentrations, and peak oxygen uptake
      (VO2 peak). Compared with usual care, the combined intervention led to
      statistically significant decreases in body weight and body fat percentage.
      Caloric restriction alone also led to significant decreases in these measures,
      but aerobic exercise alone did not. The combined intervention and each
      independent intervention also led to significant decreases in F2-isoprostane and
      IL-6 concentrations. No intervention produced significant changes in VO2 peak,
      kidney function, or urine albumin-to-creatinine ratio. In conclusion, 4-month
      dietary calorie restriction and aerobic exercise had significant, albeit
      clinically modest, benefits on body weight, fat mass, and markers of oxidative
      stress and inflammatory response in patients with moderate to severe CKD. These
      results suggest healthy lifestyle interventions as a nonpharmacologic strategy to
      improve markers of metabolic health in these patients.

PMID- 29038286
TI  - Allogeneic Mesenchymal Stem Cells for Treatment of AKI after Cardiac Surgery.
AB  - AKI after cardiac surgery remains strongly associated with mortality and lacks
      effective treatment or prevention. Preclinical studies suggest that cell-based
      interventions may influence functional recovery. We conducted a phase 2,
      randomized, double-blind, placebo-controlled trial in 27 centers across North
      America to determine the safety and efficacy of allogeneic human mesenchymal stem
      cells (MSCs) in reducing the time to recovery from AKI after cardiac surgery. We
      randomized 156 adult subjects undergoing cardiac surgery with evidence of early
      AKI to receive intra-aortic MSCs (AC607; n=67) or placebo (n=68). The primary
      outcome was the time to recovery of kidney function defined as return of
      postintervention creatinine level to baseline. The median time to recovery of
      kidney function was 15 days with AC607 and 12 days with placebo (25th, 75th
      percentile range, 10-29 versus 6-21, respectively; hazard ratio, 0.81; 95%
      confidence interval, 0.53 to 1.24; P=0.32). We did not detect a significant
      difference between groups in 30-day all-cause mortality (16.7% with AC607; 11.8%
      with placebo) or dialysis (10.6% with AC607; 7.4% with placebo). At follow-up, 12
      patients who received AC607 and six patients who received placebo had died. Rates
      of other adverse events did not differ between groups. In these patients with AKI
      after cardiac surgery, administration of allogeneic MSCs did not decrease the
      time to recovery of kidney function. Our results contrast with those in
      preclinical studies and provide important information regarding the potential
      effects of MSCs in this setting.

PMID- 29038287
TI  - Genetic Complexity of Autosomal Dominant Polycystic Kidney and Liver Diseases.
AB  - Data indicate significant phenotypic and genotypic overlap, plus a common
      pathogenesis, between two groups of inherited disorders, autosomal dominant
      polycystic kidney diseases (ADPKD), a significant cause of ESRD, and autosomal
      dominant polycystic liver diseases (ADPLD), which result in significant PLD with
      minimal PKD. Eight genes have been associated with ADPKD (PKD1 and PKD2), ADPLD
      (PRKCSH, SEC63, LRP5, ALG8, and SEC61B), or both (GANAB). Although genetics is
      only infrequently used for diagnosing these diseases and prognosing the
      associated outcomes, its value is beginning to be appreciated, and the genomics
      revolution promises more reliable and less expensive molecular diagnostic tools
      for these diseases. We therefore propose categorization of patients with a
      phenotypic and genotypic descriptor that will clarify etiology, provide
      prognostic information, and better describe atypical cases. In genetically
      defined cases, the designation would include the disease and gene names, with
      allelic (truncating/nontruncating) information included for PKD1 Recent data have
      shown that biallelic disease including at least one weak ADPKD allele is a
      significant cause of symptomatic, very early onset ADPKD. Including a genic (and
      allelic) descriptor with the disease name will provide outcome clues, guide
      treatment, and aid prevalence estimates.

PMID- 29038289
TI  - Trump signs executive orders in bid to undermine Obamacare.

PMID- 29038288
TI  - Ets in the Kidney-Unraveling the Molecular Mechanism Underlying Renal Damage in
      Salt-Sensitive Hypertension.

PMID- 29038290
TI  - New cerebral findings in infants with congenital Zika syndrome.

PMID- 29038291
TI  - Cystine uptake through the cystine/glutamate antiporter xCT triggers glioblastoma
      cell death under glucose deprivation.
AB  - Oncogenic signaling in cancer cells alters glucose uptake and utilization to
      supply sufficient energy and biosynthetic intermediates for survival and
      sustained proliferation. Oncogenic signaling also prevents oxidative stress and
      cell death caused by increased production of reactive oxygen species. However,
      elevated glucose metabolism in cancer cells, especially in glioblastoma, results
      in the cells becoming sensitive to glucose deprivation (i.e. in high glucose
      dependence), which rapidly induces cell death. However, the precise mechanism of
      this type of cell death remains unknown. Here, we report that glucose deprivation
      alone does not trigger glioblastoma cell death. We found that, for cell death to
      occur in glucose-deprived glioblastoma cells, cystine and glutamine also need to
      be present in culture media. We observed that cystine uptake through the
      cystine/glutamate antiporter xCT under glucose deprivation rapidly induces NADPH
      depletion, reactive oxygen species accumulation, and cell death. We conclude that
      although cystine uptake is crucial for production of antioxidant glutathione in
      cancer cells its transport through xCT also induces oxidative stress and cell
      death in glucose-deprived glioblastoma cells. Combining inhibitors targeting
      cancer-specific glucose metabolism with cystine and glutamine treatment may offer
      a therapeutic approach for glioblastoma tumors exhibiting high xCT expression.

PMID- 29038292
TI  - Proteolysis suppresses spontaneous prion generation in yeast.
AB  - Prions are infectious proteins that cause fatal neurodegenerative disorders
      including Creutzfeldt-Jakob and bovine spongiform encephalopathy (mad cow)
      diseases. The yeast [PSI+] prion is formed by the translation-termination factor
      Sup35, is the best-studied prion, and provides a useful model system for studying
      such diseases. However, despite recent progress in the understanding of prion
      diseases, the cellular defense mechanism against prions has not been elucidated.
      Here, we report that proteolytic cleavage of Sup35 suppresses spontaneous de novo
      generation of the [PSI+] prion. We found that during yeast growth in glucose
      media, a maximum of 40% of Sup35 is cleaved at its N-terminal prion domain. This
      cleavage requires the vacuolar proteases PrA-PrB. Cleavage occurs in a manner
      dependent on translation but independently of autophagy between the
      glutamine/asparagine-rich (Q/N-rich) stretch critical for prion formation and the
      oligopeptide-repeat region required for prion maintenance, resulting in the
      removal of the Q/N-rich stretch from the Sup35 N terminus. The complete
      inhibition of Sup35 cleavage, by knocking out either PrA (pep4Delta) or PrB
      (prb1Delta), increased the rate of de novo formation of [PSI+] prion up to ~5
      fold, whereas the activation of Sup35 cleavage, by overproducing PrB, inhibited
      [PSI+] formation. On the other hand, activation of the PrB pathway neither
      cleaved the amyloid conformers of Sup35 in [PSI+] strains nor eliminated
      preexisting [PSI+]. These findings point to a mechanism antagonizing prion
      generation in yeast. Our results underscore the usefulness of the yeast [PSI+]
      prion as a model system to investigate defense mechanisms against prion diseases
      and other amyloidoses.

PMID- 29038293
TI  - Loss of hepatic AMP-activated protein kinase impedes the rate of glycogenolysis
      but not gluconeogenic fluxes in exercising mice.
AB  - Pathologies including diabetes and conditions such as exercise place an unusual
      demand on liver energy metabolism, and this demand induces a state of energy
      discharge. Hepatic AMP-activated protein kinase (AMPK) has been proposed to
      inhibit anabolic processes such as gluconeogenesis in response to cellular energy
      stress. However, both AMPK activation and glucose release from the liver are
      increased during exercise. Here, we sought to test the role of hepatic AMPK in
      the regulation of in vivo glucose-producing and citric acid cycle-related fluxes
      during an acute bout of muscular work. We used 2H/13C metabolic flux analysis to
      quantify intermediary metabolism fluxes in both sedentary and treadmill-running
      mice. Additionally, liver-specific AMPK alpha1 and alpha2 subunit KO and WT mice
      were utilized. Exercise caused an increase in endogenous glucose production,
      glycogenolysis, and gluconeogenesis from phosphoenolpyruvate. Citric acid cycle
      fluxes, pyruvate cycling, anaplerosis, and cataplerosis were also elevated during
      this exercise. Sedentary nutrient fluxes in the postabsorptive state were
      comparable for the WT and KO mice. However, the increment in the endogenous rate
      of glucose appearance during exercise was blunted in the KO mice because of a
      diminished glycogenolytic flux. This lower rate of glycogenolysis was associated
      with lower hepatic glycogen content before the onset of exercise and prompted a
      reduction in arterial glucose during exercise. These results indicate that liver
      AMPKalpha1alpha2 is required for maintaining glucose homeostasis during an acute
      bout of exercise.

PMID- 29038294
TI  - The NSAID allosteric site of human cytosolic sulfotransferases.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly
      prescribed drugs worldwide-more than 111 million prescriptions were written in
      the United States in 2014. NSAIDs allosterically inhibit cytosolic
      sulfotransferases (SULTs) with high specificity and therapeutically relevant
      affinities. This study focuses on the interactions of SULT1A1 and mefenamic acid
      (MEF)-a potent, highly specific NSAID inhibitor of 1A1. Here, the first structure
      of an NSAID allosteric site-the MEF-binding site of SULT1A1-is determined using
      spin-label triangulation NMR. The structure is confirmed by site-directed
      mutagenesis and provides a molecular framework for understanding NSAID binding
      and isoform specificity. The mechanism of NSAID inhibition is explored using
      molecular dynamics and equilibrium and pre-steady-state ligand-binding studies.
      MEF inhibits SULT1A1 turnover through an indirect (helix-mediated) stabilization
      of the closed form of the active-site cap of the enzyme, which traps the
      nucleotide and slows its release. Using the NSAID-binding site structure of
      SULT1A1 as a comparative model, it appears that 11 of the 13 human SULT isoforms
      harbor an NSAID-binding site. We hypothesize that these sites evolved to enable
      SULT isoforms to respond to metabolites that lie within their metabolic domains.
      Finally, the NSAID-binding site structure offers a template for developing
      isozyme-specific allosteric inhibitors that can be used to regulate specific
      areas of sulfuryl-transfer metabolism.

PMID- 29038295
TI  - Characterization of aromatic residue-controlled protein retention in the
      endoplasmic reticulum of Saccharomyces cerevisiae.
AB  - An endoplasmic reticulum (ER) retention sequence (ERS) is a characteristic short
      sequence that mediates protein retention in the ER of eukaryotic cells. However,
      little is known about the detailed molecular mechanism involved in ERS-mediated
      protein ER retention. Using a new surface display-based fluorescence technique
      that effectively quantifies ERS-promoted protein ER retention within
      Saccharomyces cerevisiae cells, we performed comprehensive ERS analyses. We found
      that the length, type of amino acid residue, and additional residues at positions
      -5 and -6 of the C-terminal HDEL motif all determined the retention of ERS in the
      yeast ER. Moreover, the biochemical results guided by structure simulation
      revealed that aromatic residues (Phe-54, Trp-56, and other aromatic residues
      facing the ER lumen) in both the ERS (at positions -6 and -4) and its receptor,
      Erd2, jointly determined their interaction with each other. Our studies also
      revealed that this aromatic residue interaction might lead to the discriminative
      recognition of HDEL or KDEL as ERS in yeast or human cells, respectively. Our
      findings expand the understanding of ERS-mediated residence of proteins in the ER
      and may guide future research into protein folding, modification, and
      translocation affected by ER retention.

PMID- 29038296
TI  - A Blueprint to Advance Colorectal Cancer Immunotherapies.
AB  - Immunotherapy is rapidly becoming a standard of care for many cancers. However,
      colorectal cancer had been generally resistant to immunotherapy, despite features
      in common with sensitive tumors. Observations of substantial clinical activity
      for checkpoint blockade in colorectal cancers with defective mismatch repair
      (microsatellite instability-high tumors) have reignited interest in the search
      for immunotherapies that could be extended to the larger microsatellite stable
      (MSS) population. The Cancer Research Institute and Fight Colorectal Cancer
      convened a group of scientists, clinicians, advocates, and industry experts in
      colorectal cancer and immunotherapy to compile ongoing research efforts, identify
      gaps in translational and clinical research, and provide a blueprint to advance
      immunotherapy. We identified lack of a T-cell inflamed phenotype (due to
      inadequate T-cell infiltration, inadequate T-cell activation, or T-cell
      suppression) as a broad potential explanation for failure of checkpoint blockade
      in MSS. The specific cellular and molecular underpinnings for these various
      mechanisms are unclear. Whether biomarkers with prognostic value, such as the
      immunoscores and IFN signatures, would also predict benefit for immunotherapies
      in MSS colon cancer is unknown, but if so, these and other biomarkers for
      measuring the potential for an immune response in patients with colorectal cancer
      will need to be incorporated into clinical guidelines. We have proposed a
      framework for research to identify immunologic factors that may be modulated to
      improve immunotherapy for colorectal cancer patients, with the goal that the
      biomarkers and treatment strategies identified will become part of the routine
      management of colorectal cancer. Cancer Immunol Res; 5(11); 942-9. (c)2017 AACR.

PMID- 29038297
TI  - Tumor PDCD1LG2 (PD-L2) Expression and the Lymphocytic Reaction to Colorectal
      Cancer.
AB  - Expression of the immune checkpoint ligand CD274 (programmed cell death 1 ligand
      1, PD-L1, from gene CD274) contributes to suppression of antitumor T cell
      mediated immune response in various tumor types. However, the role of PDCD1LG2
      (PD-L2, CD273, from gene PDCD1LG2) in the tumor microenvironment remains unclear.
      We hypothesized that tumor PDCD1LG2 expression might be inversely associated with
      lymphocytic reactions to colorectal cancer. We examined tumor PDCD1LG2 expression
      by IHC in 823 colon and rectal carcinoma cases within two U.S.-nationwide cohort
      studies and categorized tumors into quartiles according to the percentage of
      PDCD1LG2-expressing carcinoma cells. We conducted multivariable ordinal logistic
      regression analysis to assess the associations of tumor PDCD1LG2 expression with
      Crohn-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral
      periglandular reaction, or tumor-infiltrating lymphocytes, controlling for
      potential confounders, including microsatellite instability, CpG island
      methylator phenotype, long-interspersed nucleotide element-1 methylation, and
      KRAS, BRAF, and PIK3CA mutations. Tumor PDCD1LG2 expression was inversely
      associated with Crohn-like lymphoid reaction (Ptrend = 0.0003). For a unit
      increase in the three-tiered ordinal categories of Crohn-like lymphoid reaction,
      a multivariable OR in the highest (vs. lowest) quartile of the percentage of
      PDCD1LG2-expressing tumor cells was 0.38 (95% confidence interval, 0.22-0.67).
      Tumor PDCD1LG2 expression was not associated with peritumoral lymphocytic
      reaction, intratumoral periglandular reaction, tumor-infiltrating lymphocytes, or
      patient survival (Ptrend > 0.13). Thus, tumor PDCD1LG2 expression is inversely
      associated with Crohn-like lymphoid reaction to colorectal cancer, suggesting a
      possible role of PDCD1LG2-expressing tumor cells in inhibiting the development of
      tertiary lymphoid tissues during colorectal carcinogenesis. Cancer Immunol Res;
      5(11); 1046-55. (c)2017 AACR.

PMID- 29038298
TI  - Subversion of NK-cell and TNFalpha Immune Surveillance Drives Tumor Recurrence.
AB  - Understanding how incompletely cleared primary tumors transition from minimal
      residual disease (MRD) into treatment-resistant, immune-invisible recurrences has
      major clinical significance. We show here that this transition is mediated
      through the subversion of two key elements of innate immunosurveillance. In the
      first, the role of TNFalpha changes from an antitumor effector against primary
      tumors into a growth promoter for MRD. Second, whereas primary tumors induced a
      natural killer (NK)-mediated cytokine response characterized by low IL6 and
      elevated IFNgamma, PD-L1hi MRD cells promoted the secretion of IL6 but minimal
      IFNgamma, inhibiting both NK-cell and T-cell surveillance. Tumor recurrence was
      promoted by trauma- or infection-like stimuli inducing VEGF and TNFalpha, which
      stimulated the growth of MRD tumors. Finally, therapies that blocked PD-1,
      TNFalpha, or NK cells delayed or prevented recurrence. These data show how innate
      immunosurveillance mechanisms, which control infection and growth of primary
      tumors, are exploited by recurrent, competent tumors and identify therapeutic
      targets in patients with MRD known to be at high risk of relapse. Cancer Immunol
      Res; 5(11); 1029-45. (c)2017 AACR.

PMID- 29038299
TI  - An Assessment in SpondyloArthritis International Society (ASAS)-endorsed
      definition of clinically important worsening in axial spondyloarthritis based on
      ASDAS.
AB  - INTRODUCTION: In a previous phase, 12 draft definitions for clinically important
      worsening in axial spondyloarthritis (axSpA) were selected, of which 3 were based
      on absolute changes in Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP
      (ASDAS). The objective here was to select the best cut-off for ASDAS for
      clinically important worsening in axSpA for use in clinical trials and
      observational studies. METHODS: An international longitudinal prospective study
      evaluating stable patients with axSpA was conducted. Data necessary to calculate
      ASDAS were collected at two consecutive visits (spaced 7 days to 6 months).
      Sensitivity and specificity of the three cut-offs for change in ASDAS were tested
      against the patient's subjective assessment of worsening as the external standard
      (ie, the patient reporting that he had worsened and felt a need for treatment
      intensification). Final selection was made by a consensus and voting procedure
      among Assessment of SpondyloArthritis International Society (ASAS) members.
      RESULTS: In total, 1169 patients with axSpA were analysed: 64.8% were male and
      had a mean age of 41.7 (SD 12.4) years. At the second visit, 127 (10.9%) patients
      judged their situation as worsened.Sensitivity and specificity for an increase of
      at least 0.6, 0.9 and 1.1 ASDAS points to detect patient-reported worsening were
      0.55 (Se) and 0.91 (Sp), 0.38 (Se) and 0.96 (Sp), and 0.33 (Se) and 0.98 (Sp),
      respectively. The ASAS consensus was to define clinically important worsening as
      an increase in ASDAS of at least 0.9 points. CONCLUSION: This data-driven ASAS
      consensus process resulted in an ASDAS-based cut-off value defining clinically
      important worsening in axSpA for use in trials.

PMID- 29038301
TI  - The small GTPase RSG1 controls a final step in primary cilia initiation.
AB  - Primary cilia, which are essential for normal development and tissue homeostasis,
      are extensions of the mother centriole, but the mechanisms that remodel the
      centriole to promote cilia initiation are poorly understood. Here we show that
      mouse embryos that lack the small guanosine triphosphatase RSG1 die at embryonic
      day 12.5, with developmental abnormalities characteristic of decreased cilia
      dependent Hedgehog signaling. Rsg1 mutant embryos have fewer primary cilia than
      wild-type embryos, but the cilia that form are of normal length and traffic
      Hedgehog pathway proteins within the cilium correctly. Rsg1 mother centrioles
      recruit proteins required for cilia initiation and dock onto ciliary vesicles,
      but axonemal microtubules fail to elongate normally. RSG1 localizes to the mother
      centriole in a process that depends on tau tubulin kinase 2 (TTBK2), the CPLANE
      complex protein Inturned (INTU), and its own GTPase activity. The data suggest a
      specific role for RSG1 in the final maturation of the mother centriole and
      ciliary vesicle that allows extension of the ciliary axoneme.

PMID- 29038302
TI  - Cullin-3 and its adaptor protein ANKFY1 determine the surface level of integrin
      beta1 in endothelial cells.
AB  - Angiogenesis, the formation of new blood vessels from the pre-existing
      vasculature, is related to numerous pathophysiological events. We previously
      reported that a RING ubiquitin ligase complex scaffold protein, cullin-3 (CUL3),
      and one of its adaptor proteins, BAZF, regulated angiogenesis in the mouse retina
      by suppressing Notch signaling. However, the degree of inhibition of angiogenesis
      was made greater by CUL3 depletion than by BAZF depletion, suggesting other roles
      of CUL3 in angiogenesis besides the regulation of Notch signaling. In the present
      study, we found that CUL3 was critical for the cell surface level of integrin
      beta1, an essential cell adhesion molecule for angiogenesis in HUVECs. By siRNA
      screening of 175 BTBPs, a family of adaptor proteins for CUL3, we found that
      ANKFY1/Rabankyrin-5, an early endosomal BTBP, was also critical for localization
      of surface integrin beta1 and angiogenesis. CUL3 interacted with ANKFY1 and was
      required for the early endosomal localization of ANKFY1. These data suggest that
      CUL3/ANKFY1 regulates endosomal membrane traffic of integrin beta1. Our results
      highlight the multiple roles of CUL3 in angiogenesis, which are mediated through
      distinct CUL3-adaptor proteins.

PMID- 29038303
TI  - F-actin reorganization by V-ATPase inhibition in prostate cancer.
AB  - The vacuolar ATPase (V-ATPase) proton pump sustains cellular pH homeostasis, and
      its inhibition triggers numerous stress responses. However, the cellular
      mechanisms involved remain largely elusive in cancer cells. We studied V-ATPase
      in the prostate cancer (PCa) cell line PC-3, which has characteristics of highly
      metastatic PCa. V-ATPase inhibitors impaired endo-lysosomal pH, vesicle
      trafficking, migration, and invasion. V-ATPase accrual in the Golgi and recycling
      endosomes suggests that traffic of internalized membrane vesicles back to the
      plasma membrane was particularly impaired. Directed movement provoked co
      localization of V-ATPase containing vesicles with F-actin near the leading edge
      of migrating cells. V-ATPase inhibition prompted prominent F-actin cytoskeleton
      reorganization. Filopodial projections were reduced, which related to reduced
      migration velocity. F-actin formed novel cytoplasmic rings. F-actin rings
      increased with extended exposure to sublethal concentrations of V-ATPase
      inhibitors, from 24 to 48 h, as the amount of alkalinized endo-lysosomal vesicles
      increased. Studies with chloroquine indicated that F-actin rings formation was pH
      dependent. We hypothesize that these novel F-actin rings assemble to overcome
      widespread traffic defects caused by V-ATPase inhibition, similar to F-actin
      rings on the surface of exocytic organelles.

PMID- 29038305
TI  - Variations in basement membrane mechanics are linked to epithelial morphogenesis.
AB  - The regulation of morphogenesis by the basement membrane (BM) may rely on changes
      in its mechanical properties. To test this, we developed an atomic force
      microscopy-based method to measure BM mechanical stiffness during two key
      processes in Drosophila ovarian follicle development. First, follicle elongation
      depends on epithelial cells that collectively migrate, secreting BM fibrils
      perpendicularly to the anteroposterior axis. Our data show that BM stiffness
      increases during this migration and that fibril incorporation enhances BM
      stiffness. In addition, stiffness heterogeneity, due to oriented fibrils, is
      important for egg elongation. Second, epithelial cells change their shape from
      cuboidal to either squamous or columnar. We prove that BM softens around the
      squamous cells and that this softening depends on the TGFbeta pathway. We also
      demonstrate that interactions between BM constituents are necessary for cell
      flattening. Altogether, these results show that BM mechanical properties are
      modified during development and that, in turn, such mechanical modifications
      influence both cell and tissue shapes.

PMID- 29038306
TI  - PFKFB4 control of AKT signaling is essential for premigratory and migratory
      neural crest formation.
AB  - Neural crest (NC) specification comprises an early phase, initiating immature NC
      progenitors formation at neural plate stage, and a later phase at neural fold
      stage, resulting in a functional premigratory NC that is able to delaminate and
      migrate. We found that the NC gene regulatory network triggers upregulation of
      pfkfb4 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4) during this late
      specification phase. As shown in previous studies, PFKFB4 controls AKT signaling
      in gastrulas and glycolysis rate in adult cells. Here, we focus on PFKFB4
      function in NC during and after neurulation, using time-controlled or hypomorph
      depletions in vivo We find that PFKFB4 is essential both for specification of
      functional premigratory NC and for its migration. PFKFB4-depleted embryos fail to
      activate n-cadherin and late NC specifiers, and exhibit severe migration defects
      resulting in craniofacial defects. AKT signaling mediates PFKFB4 function in NC
      late specification, whereas both AKT signaling and glycolysis regulate migration.
      These findings highlight novel and essential roles of PFKFB4 activity in later
      stages of NC development that are wired into the NC gene regulatory network.

PMID- 29038307
TI  - Branching morphogenesis in the developing kidney is governed by rules that
      pattern the ureteric tree.
AB  - Metanephric kidney development is orchestrated by the iterative branching
      morphogenesis of the ureteric bud. We describe an underlying patterning
      associated with the ramification of this structure and show that this pattern is
      conserved between developing kidneys, in different parts of the organ and across
      developmental time. This regularity is associated with a highly reproducible
      branching asymmetry that is consistent with locally operative growth mechanisms.
      We then develop a class of tip state models to represent elaboration of the
      ureteric tree and describe rules for 'half-delay' branching morphogenesis that
      describe almost perfectly the patterning of this structure. Spatial analysis
      suggests that the observed asymmetry may arise from mutual suppression of
      bifurcation, but not extension, between the growing ureteric tips, and
      demonstrates that disruption of patterning occurs in mouse mutants in which the
      distribution of tips on the surface of the kidney is altered. These findings
      demonstrate that kidney development occurs by way of a highly conserved
      reiterative pattern of asymmetric bifurcation that is governed by intrinsic and
      locally operative mechanisms.

PMID- 29038308
TI  - Cell dynamics underlying oriented growth of the Drosophila wing imaginal disc.
AB  - Quantitative analysis of the dynamic cellular mechanisms shaping the Drosophila
      wing during its larval growth phase has been limited, impeding our ability to
      understand how morphogen patterns regulate tissue shape. Such analysis requires
      explants to be imaged under conditions that maintain both growth and patterning,
      as well as methods to quantify how much cellular behaviors change tissue shape.
      Here, we demonstrate a key requirement for the steroid hormone 20-hydroxyecdysone
      (20E) in the maintenance of numerous patterning systems in vivo and in explant
      culture. We find that low concentrations of 20E support prolonged proliferation
      in explanted wing discs in the absence of insulin, incidentally providing novel
      insight into the hormonal regulation of imaginal growth. We use 20E-containing
      media to observe growth directly and to apply recently developed methods for
      quantitatively decomposing tissue shape changes into cellular contributions. We
      discover that whereas cell divisions drive tissue expansion along one axis, their
      contribution to expansion along the orthogonal axis is cancelled by cell
      rearrangements and cell shape changes. This finding raises the possibility that
      anisotropic mechanical constraints contribute to growth orientation in the wing
      disc.

PMID- 29038310
TI  - Free-ranging dogs prefer petting over food in repeated interactions with
      unfamiliar humans.
AB  - Dogs (Canis lupus familiaris) are the first species to have been domesticated
      and, unlike other domesticated species, they have developed a special bond with
      their owners. The ability to respond to human gestures and language, and the
      hypersocial behaviours of dogs are considered key factors that have led them to
      become man's best friend. Free-ranging dogs provide an excellent model system for
      understanding the dog-human relationship in various social contexts. In India,
      free-ranging dogs occur in all possible human habitations. They scavenge among
      garbage, beg for food from humans, give birth in dens close to human habitations,
      and establish social bonds with people. However, there is ample dog-human
      conflict on the streets, leading to morbidity and mortality of dogs. Hence, the
      ability to assess an unfamiliar human before establishing physical contact could
      be adaptive for dogs, especially in the urban environment. We tested a total of
      103 adult dogs to investigate their response to immediate social and long-term
      food and social rewards. The dogs were provided a choice of obtaining food either
      from an experimenter's hand or the ground. The dogs avoided making physical
      contact with the unfamiliar human. While immediate social reward was not
      effective in changing this response, the long-term test showed a strong effect of
      social contact. Our results revealed that these dogs tend to build trust based on
      affection, not food. This study provides significant insights into the dynamics
      of dog-human interactions on the streets and subsequent changes in behaviour of
      dogs through the process of learning.

PMID- 29038309
TI  - Deletion of Protein Kinase D1 in Pancreatic beta-Cells Impairs Insulin Secretion
      in High-Fat Diet-Fed Mice.
AB  - Betabeta-Cell adaptation to insulin resistance is necessary to maintain glucose
      homeostasis in obesity. Failure of this mechanism is a hallmark of type 2
      diabetes (T2D). Hence, factors controlling functional beta-cell compensation are
      potentially important targets for the treatment of T2D. Protein kinase D1 (PKD1)
      integrates diverse signals in the beta-cell and plays a critical role in the
      control of insulin secretion. However, the role of beta-cell PKD1 in glucose
      homeostasis in vivo is essentially unknown. Using beta-cell-specific, inducible
      PKD1 knockout mice (betaPKD1KO), we examined the role of beta-cell PKD1 under
      basal conditions and during high-fat feeding. betaPKD1KO mice under a chow diet
      presented no significant difference in glucose tolerance or insulin secretion
      compared with mice expressing the Cre transgene alone; however, when compared
      with wild-type mice, both groups developed glucose intolerance. Under a high-fat
      diet, deletion of PKD1 in beta-cells worsened hyperglycemia, hyperinsulinemia,
      and glucose intolerance. This was accompanied by impaired glucose-induced insulin
      secretion both in vivo in hyperglycemic clamps and ex vivo in isolated islets
      from high-fat diet-fed betaPKD1KO mice without changes in islet mass. This study
      demonstrates an essential role for PKD1 in the beta-cell adaptive secretory
      response to high-fat feeding in mice.

PMID- 29038311
TI  - Integration of swimming kinematics and ram suspension feeding in a model American
      paddlefish, Polyodon spathula.
AB  - Ram suspension-feeding fishes swim with an open mouth to force water through the
      oral cavity and extract prey items that are too small to be pursued individually.
      Recent research has indicated that, rather than using a dead-end mechanical
      sieve, American paddlefish (Polyodon spathula) employ vortical cross-step
      filtration. In this filtration mechanism, vortical flow that is generated
      posterior to the branchial arches organizes crossflow filtration processes into a
      spatial structure across the gill rakers. Despite the known impact of locomotor
      kinematics on fluid flow around the bodies of swimming fish, the effects of
      locomotor kinematics on filtration mechanisms in ram suspension feeders are
      unknown. Potential temporal organization of filtration mechanisms in ram
      suspension-feeding fish has not been studied previously. We investigated the
      effects of locomotor kinematics associated with undulatory swimming on intra-oral
      flow patterns and food particle transport. A mechanized model of the oral cavity
      was used to simulate the swimming kinematics of suspension-feeding paddlefish. We
      recorded fluctuations of flow speed and pressure within the model, which occurred
      at a frequency that corresponded with the frequency of the model's strides. Using
      the mechanized model in a flow tank seeded with Artemia cysts, we also showed
      that swimming kinematics aided the transport of this simulated food to the
      posterior margins of the gill slots, although the time scale of this transport is
      expected to vary with prey parameters such as size and concentration. Dye stream
      experiments revealed that, although stable vortical flow formed because of flow
      separation downstream of backward-facing steps in control trials, vortical flow
      structures in mechanized trials repeatedly formed and shed. These findings
      suggest strong integration between locomotor and feeding systems in ram
      suspension-feeding fishes.

PMID- 29038313
TI  - Defamation lawsuits: academic sword or shield?

PMID- 29038314
TI  - Physical Activity Reduces Risk of Premature Mortality in Patients With Type 1
      Diabetes With and Without Kidney Disease.
AB  - OBJECTIVE: The aims of the study were to assess how baseline leisure-time
      physical activity (LTPA) and its exercise components intensity, duration, and
      frequency are associated with all-cause and cardiovascular mortality in patients
      with type 1 diabetes 1) overall, 2) stratified by presence or absence of chronic
      kidney disease (CKD), and 3) stratified by sex. RESEARCH DESIGN AND METHODS: The
      study design was prospective and observational and included 2,639 patients with
      type 1 diabetes from the ongoing nationwide multicenter Finnish Diabetic
      Nephropathy (FinnDiane) Study. Mean follow-up time was 11.4 +/- 3.5 years. LTPA
      was assessed by using a validated self-report questionnaire. Three hundred ten
      patients (11.7%) had CKD defined as an estimated glomerular filtration rate of
      <=60 mL/min/1.73 m2. RESULTS: During follow-up, 270 deaths occurred. LTPA and all
      its components were associated with all-cause mortality, even after adjustment
      for the potential confounders sex, diabetic nephropathy, duration of diabetes,
      age at onset of diabetes, systolic blood pressure, triglycerides, BMI, and HbA1c.
      Only exercise intensity was associated with cardiovascular mortality after
      adjustment for the confounders. Of the patients with CKD, 127 died during follow
      up. The total amount of LTPA and exercise frequency were independently associated
      with lower risk of all-cause mortality when adjusted for covariates. CONCLUSIONS:
      Exercise is associated with a lower risk of premature all-cause and
      cardiovascular mortality in patients with type 1 diabetes. This study also
      demonstrates that physical activity is associated with a lower risk of mortality
      in patients with type 1 diabetes and CKD.

PMID- 29038312
TI  - Dynamic stroma reorganization drives blood vessel dysmorphia during glioma
      growth.
AB  - Glioma growth and progression are characterized by abundant development of blood
      vessels that are highly aberrant and poorly functional, with detrimental
      consequences for drug delivery efficacy. The mechanisms driving this vessel
      dysmorphia during tumor progression are poorly understood. Using longitudinal
      intravital imaging in a mouse glioma model, we identify that dynamic sprouting
      and functional morphogenesis of a highly branched vessel network characterize the
      initial tumor growth, dramatically changing to vessel expansion, leakage, and
      loss of branching complexity in the later stages. This vascular phenotype
      transition was accompanied by recruitment of predominantly pro-inflammatory M1
      like macrophages in the early stages, followed by in situ repolarization to M2
      like macrophages, which produced VEGF-A and relocate to perivascular areas. A
      similar enrichment and perivascular accumulation of M2 versus M1 macrophages
      correlated with vessel dilation and malignancy in human glioma samples of
      different WHO malignancy grade. Targeting macrophages using anti-CSF1 treatment
      restored normal blood vessel patterning and function. Combination treatment with
      chemotherapy showed survival benefit, suggesting that targeting macrophages as
      the key driver of blood vessel dysmorphia in glioma progression presents
      opportunities to improve efficacy of chemotherapeutic agents. We propose that
      vessel dysfunction is not simply a general feature of tumor vessel formation, but
      rather an emergent property resulting from a dynamic and functional
      reorganization of the tumor stroma and its angiogenic influences.

PMID- 29038316
TI  - Using perinatal morbidity scoring tools as a primary study outcome.
AB  - Perinatal morbidity scores are tools that score or weight different adverse
      events according to their relative severity. Perinatal morbidity scores are
      appealing for maternal-infant health researchers because they provide a way to
      capture a broad range of adverse events to mother and newborn while recognising
      that some events are considered more serious than others. However, they have
      proved difficult to implement as a primary outcome in applied research studies
      because of challenges in testing if the scores are significantly different
      between two or more study groups. We outline these challenges and describe a
      solution, based on Poisson regression, that allows differences in perinatal
      morbidity scores to be formally evaluated. The approach is illustrated using an
      existing maternal-neonatal scoring tool, the Adverse Outcome Index, to evaluate
      the safety of labour and delivery before and after the closure of obstetrical
      services in small rural communities. Applying the proposed Poisson regression to
      the case study showed a protective risk ratio for adverse outcome following
      closures as compared with the original analysis, where no difference was found.
      This approach opens the door for considerably broader use of perinatal morbidity
      scoring tools as a primary outcome in applied population and clinical maternal
      infant health research studies.

PMID- 29038315
TI  - Adiposity, Dysmetabolic Traits, and Earlier Onset of Female Puberty in Adolescent
      Offspring of Women With Gestational Diabetes Mellitus: A Clinical Study Within
      the Danish National Birth Cohort.
AB  - OBJECTIVE: Offspring of pregnancies affected by gestational diabetes mellitus
      (GDM) are at increased risk of the development of type 2 diabetes. However, the
      extent to which these dysmetabolic traits may be due to offspring and/or maternal
      adiposity is unknown. We examined body composition and associated cardiometabolic
      traits in 561 9- to 16-year-old offspring of mothers with GDM and 597 control
      offspring. RESEARCH DESIGN AND METHODS: We measured anthropometric
      characteristics; puberty status; blood pressure; and fasting glucose, insulin, C
      peptide, and lipid levels; and conducted a DEXA scan in a subset of the cohort.
      Differences in the outcomes between offspring of mothers with GDM and control
      subjects were examined using linear and logistic regression models. RESULTS:
      After adjustment for age and sex, offspring of mothers with GDM displayed higher
      weight, BMI, waist-to-hip ratio (WHR), systolic blood pressure, and resting heart
      rate and lower height. Offspring of mothers with GDM had higher total and
      abdominal fat percentages and lower muscle mass percentages, but these
      differences disappeared after correction for offspring BMI. The offspring of
      mothers with GDM displayed higher fasting plasma glucose, insulin, C-peptide,
      HOMA-insulin resistance (IR), and plasma triglyceride levels, whereas fasting
      plasma HDL cholesterol levels were decreased. Female offspring of mothers with
      GDM had an earlier onset of puberty than control offspring. Offspring of mothers
      with GDM had significantly higher BMI, WHR, fasting glucose, and HOMA-IR levels
      after adjustment for maternal prepregnancy BMI, and glucose and HOMA-IR remained
      elevated in the offspring of mothers with GDM after correction for both maternal
      and offspring BMIs. CONCLUSIONS: In summary, adolescent offspring of women with
      GDM show increased adiposity, an adverse cardiometabolic profile, and earlier
      onset of puberty among girls. Increased fasting glucose and HOMA-IR levels among
      the offspring of mothers with GDM may be explained by the programming effects of
      hyperglycemia in pregnancy.

PMID- 29038317
TI  - Change in non-alcoholic beverage sales following a 10-pence levy on sugar
      sweetened beverages within a national chain of restaurants in the UK: interrupted
      time series analysis of a natural experiment.
AB  - BACKGROUND: This study evaluates changes in sales of non-alcoholic beverages in
      Jamie's Italian, a national chain of commercial restaurants in the UK, following
      the introduction of a L0.10 per-beverage levy on sugar-sweetened beverages (SSBs)
      and supporting activity including beverage menu redesign, new products and
      establishment of a children's health fund from levy proceeds. METHODS: We used an
      interrupted time series design to quantify changes in sales of non-alcoholic
      beverages 12 weeks and 6 months after implementation of the levy, using itemised
      electronic point of sale data. Main outcomes were number of SSBs and other non
      alcoholic beverages sold per customer. Linear regression and multilevel random
      effects models, adjusting for seasonality and clustering, were used to
      investigate changes in SSB sales across all restaurants (n=37) and by tertiles of
      baseline restaurant SSB sales per customer. RESULTS: Compared with the prelevy
      period, the number of SSBs sold per customer declined by 11.0% (-17.3% to -4.3%)
      at 12 weeks and 9.3% (-15.2% to -3.2%) at 6 months. For non-levied beverages,
      sales per customer of children's fruit juice declined by 34.7% (-55.3% to -4.3%)
      at 12 weeks and 9.9% (-16.8% to -2.4%) at 6 months. At 6 months, sales per
      customer of fruit juice increased by 21.8% (14.0% to 30.2%) but sales of diet
      cola (-7.3%; -11.7% to -2.8%) and bottled waters (-6.5%; -11.0% to -1.7%)
      declined. Changes in sales were only observed in restaurants in the medium and
      high tertiles of baseline SSB sales per customer. CONCLUSIONS: Introduction of a
      L0.10 levy on SSBs alongside complementary activities is associated with declines
      in SSB sales per customer in the short and medium term, particularly in
      restaurants with higher baseline sales of SSBs.

PMID- 29038318
TI  - Healthy interpretation.

PMID- 29038319
TI  - We need a "made in Canada" orphan drug framework.

PMID- 29038321
TI  - Testosterone use causing erythrocytosis.

PMID- 29038322
TI  - Thumb and vallecula signs in acute infectious epiglottitis.

PMID- 29038320
TI  - Persistence of immunity after vaccination with a capsular group B meningococcal
      vaccine in 3 different toddler schedules.
AB  - BACKGROUND: One schedule for the capsular group B meningococcal vaccine 4CMenB is
      2 doses that are administered 2 months apart for children aged 12-23 months, with
      a booster dose 12-24 months later. Our objective was to provide data on
      persistence of human serum bactericidal antibody (hSBA) titres in children up to
      4 years of age after initial doses at 12-24 months, and immunogenicity of a
      booster dose at 48 months of age compared with vaccine-naive children. METHODS:
      Children previously immunized, as part of a randomized controlled trial, with 2
      doses of 4CMenB vaccine at 12-24 months of age received a booster at 4 years of
      age. Vaccine-naive age-matched toddlers received 2 doses of 4CMenB. Human serum
      bactericidal antibody titres against reference strains H44/76, 5/99, NZ98/254 and
      M10713 were evaluated before and after innoculation with 4CMenB vaccine in 4-year
      old children. RESULTS: Of 332 children in the study, 123 had previously received
      4CMenB and 209 were vaccine-naive controls. Before the booster, the proportions
      of participants (previously vaccinated groups compared with controls) with hSBA
      titres of 1:5 or more were as follows: 9%-11% v. 1% (H44/76), 84%-100% v. 4%
      (5/99), 0%-18% v. 0% (NZ98/254) and 59%-60% v. 60% (M10713). After 1 dose of
      4CMenB in previously immunized children, the proportions of participants
      achieving hSBA titres of 1:5 or more were 100% (H44/76 and 5/99), 70%-100%
      (NZ98/254) and 90%-100% (M10713). INTERPRETATION: We found that waning of hSBA
      titres by 4 years of age occurred after 2 doses of 4CMenB vaccine administered at
      12-24 months, and doses at 12-24 months have a priming effect on the immune
      system. A booster may be necessary to maintain hSBA titres of 1:5 or more among
      those children with increased disease risk. Trial registration:
      ClinicalTrials.gov, no. NCT01717638.

PMID- 29038323
TI  - Real-world data really matter.

PMID- 29038324
TI  - Federal leadership needed to realize national data set for cardiovascular care.

PMID- 29038325
TI  - Saskatchewan First Nations drafts suicide prevention plan.

PMID- 29038326
TI  - Health Canada to warn young people of cannabis risks in campaign.

PMID- 29038327
TI  - Beacon in developmental biology.

PMID- 29038328
TI  - Pay gap growing between family doctors, other specialists.

PMID- 29038329
TI  - Why public health is the most challenging specialty of all.

PMID- 29038330
TI  - Can growth hormone treatment improve growth in children with severe growth
      failure due to anorexia nervosa? A preliminary pilot study.
AB  - BACKGROUND/AIMS: Growth failure is a difficult but key aspect of care in children
      with anorexia nervosa (AN). The effects of hGH therapy have not been studied. The
      aim was to investigate the effect of hGH treatment on height velocity (HV) in
      children with AN. METHODS: We carried out a retrospective observational study.
      Ten girls diagnosed with AN at 10.0 +/- 1.9 years, with prolonged severe growth
      failure (HV < 2.5 cm/year for at least 18 months) at the age of 13.3 +/- 1.1
      years and delayed puberty after nutritional rehabilitation, were treated with hGH
      (0.040 mg/kg/day) from a bone age of 10.9 +/- 1.7 years until they reached adult
      height. Height and HV were measured before treatment and at 12-month intervals
      during treatment. RESULTS: Mean body mass index SDS remained unchanged, but HV
      increased significantly, from a median of 1.0 (0.7-2.1) to 7.1 (6.0-9.5) cm/year
      after one year (P < 0.002) and 5.6 (4.8-6.2) cm/year after two years of
      treatment. Height SDS increased from -2.2 +/- 1.3 to -1.6 +/- 1.3 after one year
      (P < 0.002) and -1.1 +/- 1.5 after two years of GH treatment. Adult height (-0.1
      +/- 1.0 SDS) was close to target height after 3.6 +/- 1.4 years of GH treatment.
      Serum IGF-I levels increased significantly during treatment (P < 0.01). The
      treatment was well tolerated. CONCLUSIONS: This proof-of-concept study shows that
      hGH treatment is associated with significant improvements in linear growth in
      adolescents with AN and severe growth failure. A randomized placebo-controlled
      trial is required to determine the ultimate impact of GH treatment in patients
      with this severe, rare condition.

PMID- 29038331
TI  - Ghrelin stimulation by hypothalamic-pituitary-adrenal axis activation depends on
      increasing cortisol levels.
AB  - Ghrelin plasma concentration increases in parallel to cortisol after a
      standardized psychological stress in humans, but the physiological basis of this
      interaction is unknown. We aimed to elucidate this question by studying the
      ghrelin response to pharmacological manipulation of the hypothalamic-pituitary
      adrenal (HPA) axis. Six lean, healthy male volunteers were examined under four
      experimental conditions. Blood samples were collected every 30 min for two
      sequential periods of two hours. Initially, a baseline period was followed by
      intravenous injection of a synthetic analog of ACTH (250 MUg). Subsequently, a
      single dose of metyrapone was administered at midnight and in the following
      morning, blood samples were collected for 2 h, followed by an intravenous
      injection of hydrocortisone (100 mg) with continued sampling. We show that
      increased cortisol serum levels secondary to ACTH stimulation or hydrocortisone
      administration are positively associated with plasma ghrelin levels, whereas
      central stimulation of the HPA axis by blocking cortisol synthesis with
      metyrapone is associated with decreased plasma ghrelin levels. Collectively, this
      suggests that HPA-axis-mediated elevations in ghrelin plasma concentration
      require increased peripheral cortisol levels, independent of central elevation of
      ACTH and possibly CRH levels.

PMID- 29038332
TI  - GATA transcription factors in testicular adrenal rest tumours.
AB  - Testicular adrenal rest tumours (TARTs) are benign adrenal-like testicular
      tumours that frequently occur in male patients with congenital adrenal
      hyperplasia. Recently, GATA transcription factors have been linked to the
      development of TARTs in mice. The aim of our study was to determine GATA
      expression in human TARTs and other steroidogenic tissues. We determined GATA
      expression in TARTs (n = 16), Leydig cell tumours (LCTs; n = 7), adrenal (foetal
      (n = 6) + adult (n = 10)) and testis (foetal (n = 13) + adult (n = 8)). We found
      testis-like GATA4, and adrenal-like GATA3 and GATA6 gene expressions by qPCR in
      human TARTs, indicating mixed testicular and adrenal characteristics of TARTs.
      Currently, no marker is available to discriminate TARTs from LCTs, leading to
      misdiagnosis and incorrect treatment. GATA3 and GATA6 mRNAs exhibited excellent
      discriminative power (area under the curve of 0.908 and 0.816, respectively),
      while immunohistochemistry did not. GATA genes contain several CREB-binding sites
      and incubation with 0.1 mM dibutyryl cAMP for 4 h stimulated GATA3, GATA4 and
      GATA6 expressions in a human foetal testis cell line (hs181.tes). Incubation of
      adrenocortical cells (H295RA) with ACTH, however, did not induce GATA expression
      in vitro Although ACTH did not dysregulate GATA expression in the only human ACTH
      sensitive in vitro model available, our results do suggest that aberrant
      expression of GATA transcription factors in human TARTs might be involved in TART
      formation.

PMID- 29038333
TI  - Germ granule-mediated RNA regulation in male germ cells.
AB  - Germ cells have exceptionally diverse transcriptomes. Furthermore, the progress
      of spermatogenesis is accompanied by dramatic changes in gene expression
      patterns, the most drastic of them being near-to-complete transcriptional
      silencing during the final steps of differentiation. Therefore, accurate RNA
      regulatory mechanisms are critical for normal spermatogenesis. Cytoplasmic germ
      cell-specific ribonucleoprotein (RNP) granules, known as germ granules,
      participate in posttranscriptional regulation in developing male germ cells.
      Particularly, germ granules provide platforms for the PIWI-interacting RNA
      (piRNA) pathway and appear to be involved both in piRNA biogenesis and piRNA
      targeted RNA degradation. Recently, other RNA regulatory mechanisms, such as the
      nonsense-mediated mRNA decay pathway have also been associated to germ granules
      providing new exciting insights into the function of germ granules. In this
      review article, we will summarize our current knowledge on the role of germ
      granules in the control of mammalian male germ cell's transcriptome and in the
      maintenance of fertility.

PMID- 29038334
TI  - Anatomy and Histology of the Human and Murine Prostate.
AB  - The human and murine prostate glands have similar functional roles in the
      generation of seminal fluid to assist in reproduction. There are significant
      differences in the anatomy and histology of murine and human prostate and
      knowledge of the normal anatomy and histology of the murine prostate is essential
      to interpreting changes in genetically engineered mouse models. In this review,
      the normal anatomy and histology of both human and mouse prostate will be
      described.

PMID- 29038335
TI  - Preclinical and Coclinical Studies in Prostate Cancer.
AB  - Men who develop metastatic castration-resistant prostate cancer (mCRPC) will
      invariably succumb to their disease. Thus there remains a pressing need for
      preclinical testing of new drugs and drug combinations for late-stage prostate
      cancer (PCa). Insights from the mCRPC genomic landscape have revealed that, in
      addition to sustained androgen receptor (AR) signaling, there are other
      actionable molecular alterations and distinct molecular subclasses of PCa;
      however, the rate at which this knowledge translates into patient care via
      current preclinical testing is painfully slow and inefficient. Here, we will
      highlight the issues involved and discuss a new translational platform, "the co
      clinical trial project," to expedite current preclinical studies and optimize
      clinical trial and experimental drug testing. With this platform, in vivo
      preclinical and early clinical studies are closely aligned, enabling in vivo
      testing of drugs using genetically engineered mouse models (GEMMs) in defined
      genetic contexts to personalize individual therapies. We will discuss the
      principles and essential components of this novel paradigm, representative
      success stories and future therapeutic options for mCRPC that should be explored.

PMID- 29038336
TI  - The K-Ras, N-Ras, and H-Ras Isoforms: Unique Conformational Preferences and
      Implications for Targeting Oncogenic Mutants.
AB  - Ras controls a multitude of cellular signaling processes, including cell
      proliferation, differentiation, and apoptosis. Deregulation of Ras cycling often
      promotes tumorigenesis and various other developmental disorders, termed
      RASopothies. Although the structure of Ras has been known for many decades, it is
      still one of the most highly sought-after drug targets today, and is often
      referred to as "undruggable." At the center of this paradoxical protein is a lack
      of understanding of fundamental differences in the G domains between the highly
      similar Ras isoforms and common oncogenic mutations, despite the immense wealth
      of knowledge accumulated about this protein to date. A shift in the field during
      the past few years toward a high-resolution understanding of the structure
      confirms the hypothesis that each isoform and oncogenic mutation must be
      considered individually, and that not all Ras mutations are created equal. For
      the first time in Ras history, we have the ability to directly compare the
      structures of each wild-type isoform to construct a "base-line" understanding,
      which can then be used as a springboard for analyzing the effects of oncogenic
      mutations on the structure-function relationship in Ras. This is a fundamental
      and large step toward the goal of developing personalized therapies for patients
      with Ras-driven cancers and diseases.

PMID- 29038337
TI  - RNA polymerase II primes Polycomb-repressed developmental genes throughout
      terminal neuronal differentiation.
AB  - Polycomb repression in mouse embryonic stem cells (ESCs) is tightly associated
      with promoter co-occupancy of RNA polymerase II (RNAPII) which is thought to
      prime genes for activation during early development. However, it is unknown
      whether RNAPII poising is a general feature of Polycomb repression, or is lost
      during differentiation. Here, we map the genome-wide occupancy of RNAPII and
      Polycomb from pluripotent ESCs to non-dividing functional dopaminergic neurons.
      We find that poised RNAPII complexes are ubiquitously present at Polycomb
      repressed genes at all stages of neuronal differentiation. We observe both loss
      and acquisition of RNAPII and Polycomb at specific groups of genes reflecting
      their silencing or activation. Strikingly, RNAPII remains poised at transcription
      factor genes which are silenced in neurons through Polycomb repression, and have
      major roles in specifying other, non-neuronal lineages. We conclude that RNAPII
      poising is intrinsically associated with Polycomb repression throughout
      differentiation. Our work suggests that the tight interplay between RNAPII
      poising and Polycomb repression not only instructs promoter state transitions,
      but also may enable promoter plasticity in differentiated cells.

PMID- 29038338
TI  - Infectious complications of CD19-targeted chimeric antigen receptor-modified T
      cell immunotherapy.
AB  - Lymphodepletion chemotherapy with CD19-targeted chimeric antigen receptor
      modified T (CAR-T)-cell immunotherapy is a novel treatment for refractory or
      relapsed B-cell malignancies. Infectious complications of this approach have not
      been systematically studied. We evaluated infections occurring between days 0 to
      90 in 133 patients treated with CD19 CAR-T cells in a phase 1/2 study. We used
      Poisson and Cox regression to evaluate pre- and posttreatment risk factors for
      infection, respectively. The cohort included patients with acute lymphoblastic
      leukemia (ALL; n = 47), chronic lymphocytic leukemia (n = 24), and non-Hodgkin
      lymphoma (n = 62). There were 43 infections in 30 of 133 patients (23%) within 28
      days after CAR-T-cell infusion with an infection density of 1.19 infections for
      every 100 days at risk. There was a lower infection density of 0.67 between days
      29 and 90 (P = .02). The first infection occurred a median of 6 days after CAR-T
      cell infusion. Six patients (5%) developed invasive fungal infections and 5
      patients (4%) had life-threatening or fatal infections. Patients with ALL, >=4
      prior antitumor regimens, and receipt of the highest CAR-T-cell dose (2 * 107
      cells per kg) had a higher infection density within 28 days in an adjusted model
      of baseline characteristics. Cytokine release syndrome (CRS) severity was the
      only factor after CAR-T-cell infusion associated with infection in a
      multivariable analysis. The incidence of infections was comparable to
      observations from clinical trials of salvage chemoimmunotherapies in similar
      patients. This trial was registered at www.clinicaltrials.gov as #NCT01865617.

PMID- 29038340
TI  - Frontline brentuximab vedotin in combination with dacarbazine or bendamustine in
      patients aged >=60 years with HL.
AB  - Patients aged >=60 years with treatment-naive Hodgkin lymphoma (HL) have few
      treatment options and inferior survival due to treatment-related toxicities and
      comorbidities. This phase 2, nonrandomized, open-label study evaluated
      brentuximab vedotin (BV) monotherapy (results previously reported), BV plus
      dacarbazine (DTIC), and BV plus bendamustine. Patients had classical HL and were
      ineligible for or declined frontline chemotherapy. Twenty-two patients received
      1.8 mg/kg BV and 375 mg/m2 DTIC for up to 12 cycles, and 20 more patients
      received 1.8 mg/kg BV plus 90 or 70 mg/m2 bendamustine for up to 6 cycles (dose
      reduced due to toxicity). Subsequent BV monotherapy was allowed. Approximately 30
      patients were to receive BV plus bendamustine; however, the incidence of serious
      adverse events (65%) and 2 deaths on study led to discontinuation of bendamustine
      and cessation of enrollment. Most patients had stage III/IV disease, and
      approximately half had >=3 comorbidities or were impaired in >=1 aspect that
      significantly interfered with quality of life. For BV plus DTIC, the objective
      response rate (ORR) was 100% and the complete remission (CR) rate was 62%. To
      date, the median progression-free survival (PFS) is 17.9 months. For BV plus
      bendamustine, the ORR was 100% and the CR rate was 88%. Neither the median PFS
      nor overall survival was reached. For elderly patients with HL, BV plus DTIC may
      be a frontline option based on tolerability and response duration. Despite
      activity, BV plus bendamustine is not a tolerable regimen in these patients. This
      trial was registered at www.clinicaltrials.gov as #NCT01716806.

PMID- 29038341
TI  - Europe steps up action against vaccine hesitancy as measles outbreaks continue.

PMID- 29038339
TI  - Reclassifying patients with early-stage Hodgkin lymphoma based on functional
      radiographic markers at presentation.
AB  - The presence of bulky disease in Hodgkin lymphoma (HL), traditionally defined
      with a 1-dimensional measurement, can change a patient's risk grouping and thus
      the treatment approach. We hypothesized that 3-dimensional measurements of
      disease burden obtained from baseline 18F-fluorodeoxyglucose positron emission
      tomography-computed tomography (PET-CT) scans, such as metabolic tumor volume
      (MTV) and total lesion glycolysis (TLG), would more accurately risk-stratify
      patients. To test this hypothesis, we reviewed pretreatment PET-CT scans of
      patients with stage I-II HL treated at our institution between 2003 and 2013.
      Disease was delineated on prechemotherapy PET-CT scans by 2 methods: (1) manual
      contouring and (2) subthresholding of these contours to give the tumor volume
      with standardized uptake value >=2.5. MTV and TLG were extracted from the
      threshold volumes (MTVt, TLGt) and from the manually contoured soft-tissue
      volumes. At a median follow-up of 4.96 years for the 267 patients evaluated, 27
      patients were diagnosed with relapsed or refractory disease and 12 died. Both
      MTVt and TLGt were highly correlated with freedom from progression and were
      dichotomized with 80th percentile cutoff values of 268 and 1703, respectively.
      Consideration of MTV and TLG enabled restratification of early unfavorable HL
      patients as having low- and high-risk disease. We conclude that MTV and TLG
      provide a potential measure of tumor burden to aid in risk stratification of
      early unfavorable HL patients.

PMID- 29038342
TI  - Health Beliefs and the Developmental Treatment Cascade.

PMID- 29038343
TI  - Beliefs Regarding Development and Early Intervention Among Low-Income African
      American and Hispanic Mothers.
AB  - OBJECTIVES: Understand the role of health beliefs in shaping maternal decisions
      regarding help-seeking for children with developmental delay (DD) and explore
      differences between African American and Hispanic mothers. METHODS: Open-ended,
      semistructured interviews were conducted with African American and Hispanic
      mothers of children aged 0 to 36 months with DD. Interviews were recorded,
      transcribed, and analyzed by using inductive content analysis. RESULTS: Mothers
      (n = 22) were African American (36%) or Hispanic (64%), 25 to 34 years old (64%),
      had less than a high school education (59%), and had children receiving public
      insurance (95%). Five major themes emerged describing the role of maternal health
      beliefs in shaping key stages of the help-seeking pathway for children with DD:
      (1) "I can see" (observing other children and making comparisons); (2) "Children
      are different and develop in their own time" (perceiving that their child might
      be different, but not necessarily delayed); (3) "It's not that I don't trust the
      doctor" (relying on social networks rather than pediatricians to inform the help
      seeking pathway); (4) "I got so much going on" (difficulty prioritizing early
      intervention [EI] because of competing stressors); and (5) limited and
      conflicting information (delaying or forgoing EI because of limited or
      conflicting information). Differences between African American and Hispanic
      mothers are also described. CONCLUSIONS: Understanding maternal health beliefs
      and expectations regarding DD and EI, acknowledging the influence of social
      networks on help-seeking, and addressing social and financial stressors are
      critical to ensuring that children with DD are identified and supported at an
      early age.

PMID- 29038345
TI  - Administering xCT Inhibitors Based on Circadian Clock Improves Antitumor Effects.
AB  - Clock genes encoding transcription factors that regulate circadian rhythms may
      inform chronomodulated chemotherapy, where time-dependent dose alterations might
      affect drug efficacy and reduce side effects. For example, inhibiting the
      essential cystine transporter xCT with sulfasalazine induces growth arrest in
      cancer cells. Although the anticancer effects of sulfasalazine have been studied
      extensively, its effects on transcriptional control of xCT expression have not
      been studied. Here, we show that sulfasalazine administration during the period
      of increased xCT expression improves its anticancer effects and that the Clock
      gene itself induces xCT expression and regulates its circadian rhythm. Our
      findings highlight the clinical potential of chronomodulated chemotherapy and the
      importance of xCT-mediated transcriptional regulation in the utility of such
      strategies. Cancer Res; 77(23); 6603-13. (c)2017 AACR.

PMID- 29038344
TI  - Blocking Myristoylation of Src Inhibits Its Kinase Activity and Suppresses
      Prostate Cancer Progression.
AB  - Protein N-myristoylation enables localization to membranes and helps maintain
      protein conformation and function. N-myristoyltransferases (NMT) catalyze co- or
      posttranslational myristoylation of Src family kinases and other oncogenic
      proteins, thereby regulating their function. In this study, we provide genetic
      and pharmacologic evidence that inhibiting the N-myristoyltransferase NMT1
      suppresses cell-cycle progression, proliferation, and malignant growth of
      prostate cancer cells. Loss of myristoylation abolished the tumorigenic potential
      of Src and its synergy with androgen receptor in mediating tumor invasion. We
      identified the myristoyl-CoA analogue B13 as a small-molecule inhibitor of NMT1
      enzymatic activity. B13 exposure blocked Src myristoylation and Src localization
      to the cytoplasmic membrane, attenuating Src-mediated oncogenic signaling. B13
      exerted its anti-invasive and antitumor effects against prostate cancer cells,
      with minimal toxic side-effects in vivo Structural optimization based on
      structure-activity relationships enabled the chemical synthesis of LCL204, with
      enhanced inhibitory potency against NMT1. Collectively, our results offer a
      preclinical proof of concept for the use of protein myristoylation inhibitors as
      a strategy to block prostate cancer progression. Cancer Res; 77(24); 6950-62.
      (c)2017 AACR.

PMID- 29038347
TI  - An Akt3 Splice Variant Lacking the Serine 472 Phosphorylation Site Promotes
      Apoptosis and Suppresses Mammary Tumorigenesis.
AB  - The Akt pathway is a well-known promoter of tumor malignancy. Akt3 is expressed
      as two alternatively spliced variants, one of which lacks the key regulatory
      serine 472 phosphorylation site. Whereas the function of full-length Akt3 isoform
      (Akt3/+S472) is well-characterized, that of Akt3/-S472 isoform remains unknown.
      Despite being expressed at a substantially lower level than Akt3/+S472 in triple
      negative breast cancer cells, specific ablation of Akt3/-S472 enhanced, whereas
      overexpression, suppressed mammary tumor growth, consistent with a significant
      association with patient survival duration relative to Akt3/+S472. These effects
      were due to striking induction of apoptosis, which was mediated by Bim
      upregulation, leading to conformational activation of Bax and caspase-3
      processing. Bim accumulation was caused by marked endocytosis of EGF receptors
      with concomitant ERK attenuation, which stabilizes BIM. These findings
      demonstrate an unexpected function of an endogenously expressed Akt isoform in
      promoting, as opposed to suppressing, apoptosis, underscoring that Akt isoforms
      may exert dissonant functions in malignancy.Significance: These results
      illuminate an unexpected function for an endogenously expressed Akt isoform in
      promoting apoptosis, underscoring the likelihood that different Akt isoforms
      exert distinct functions in human cancer. Cancer Res; 78(1); 103-14. (c)2017
      AACR.

PMID- 29038349
TI  - Correction: How tetraspanins shape endothelial and leukocyte nano-architecture
      during inflammation.

PMID- 29038346
TI  - ATR Is a Therapeutic Target in Synovial Sarcoma.
AB  - Synovial sarcoma (SS) is an aggressive soft-tissue malignancy characterized by
      expression of SS18-SSX fusions, where treatment options are limited. To identify
      therapeutically actionable genetic dependencies in SS, we performed a series of
      parallel, high-throughput small interfering RNA (siRNA) screens and compared
      genetic dependencies in SS tumor cells with those in >130 non-SS tumor cell
      lines. This approach revealed a reliance of SS tumor cells upon the DNA damage
      response serine/threonine protein kinase ATR. Clinical ATR inhibitors (ATRi)
      elicited a synthetic lethal effect in SS tumor cells and impaired growth of SS
      patient-derived xenografts. Oncogenic SS18-SSX family fusion genes are known to
      alter the composition of the BAF chromatin-remodeling complex, causing ejection
      and degradation of wild-type SS18 and the tumor suppressor SMARCB1. Expression of
      oncogenic SS18-SSX fusion proteins caused profound ATRi sensitivity and a
      reduction in SS18 and SMARCB1 protein levels, but an SSX18-SSX1 Delta71-78 fusion
      containing a C-terminal deletion did not. ATRi sensitivity in SS was
      characterized by an increase in biomarkers of replication fork stress (increased
      gammaH2AX, decreased replication fork speed, and increased R-loops), an apoptotic
      response, and a dependence upon cyclin E expression. Combinations of cisplatin or
      PARP inhibitors enhanced the antitumor cell effect of ATRi, suggesting that
      either single-agent ATRi or combination therapy involving ATRi might be further
      assessed as candidate approaches for SS treatment. Cancer Res; 77(24); 7014-26.
      (c)2017 AACR.

PMID- 29038348
TI  - STK33 Promotes Growth and Progression of Pancreatic Cancer as a Critical
      Downstream Mediator of HIF1alpha.
AB  - The serine/threonine kinase STK33 has been implicated in cancer cell
      proliferation. Here, we provide evidence of a critical role for STK33 in the
      pathogenesis and metastatic progression of pancreatic ductal adenocarcinoma
      (PDAC). STK33 expression in PDAC was regulated by the hypoxia-inducible
      transcription factor HIF1alpha. In human PDAC specimens, STK33 was overexpressed
      and associated with poor prognosis. Enforced STK33 expression promoted PDAC
      proliferation, migration, invasion, and tumor growth, whereas STK33 depletion
      exerted opposing effects. Mechanistic investigations showed that HIF1alpha
      regulated STK33 via direct binding to a hypoxia response element in its promoter.
      In showing that dysregulated HIF1alpha/STK33 signaling promotes PDAC growth and
      progression, our results suggest STK33 as a candidate therapeutic target to
      improve PDAC treatment. Cancer Res; 77(24); 6851-62. (c)2017 AACR.

PMID- 29038351
TI  - Differences in oxidative metabolism modulation induced by ischemia/reperfusion
      between trained and untrained individuals assessed by NIRS.
AB  - Endurance training is associated with skeletal muscle adaptations that regulate
      the oxidative metabolism during ischemia/reperfusion. The aim of this study was
      to noninvasively assess in vivo differences in the oxidative metabolism activity
      during ischemia/reperfusion between trained and untrained individuals, using near
      infrared spectroscopy (NIRS) combined with a vascular occlusion test (VOT)
      technique (NIRS-VOT). Sixteen untrained (26.3 +/- 5.1 year) and seventeen trained
      (29.4 +/- 4.9 year) healthy young adult men were submitted to a VOT (2 min
      baseline, 5 min occlusion, and 8 min reperfusion). Oxygen utilization was
      estimated from the area under the curve of the NIRS-derived deoxyhemoglobin [HHb]
      signal during occlusion (AUCocc). Muscle reperfusion was derived from the area
      above the curve (AACrep) of the [HHb] signal after cuff release. The AUCocc of
      the untrained participants (21010 +/- 9553 % . s) was significantly larger than
      the AUCocc of their trained counterparts (12320 +/- 3283 % . s); P = 0.001). The
      AACrep of the untrained participants (5928 +/- 3769 % . s) was significantly
      larger than the AACrep of the trained participants (3745 +/- 1900 % . s; P =
      0.042). There was a significant correlation between AUCocc and AACrep (r = 0.840;
      P = 0.001). NIRS assessment of oxidative metabolism showed that trained
      individuals are more efficient in shifting between oxidative and anaerobic
      metabolism in response to ischemia and reperfusion.

PMID- 29038350
TI  - Male apoE*3-Leiden.CETP mice on high-fat high-cholesterol diet exhibit a biphasic
      dyslipidemic response, mimicking the changes in plasma lipids observed through
      life in men.
AB  - Physiological adaptations resulting in the development of the metabolic syndrome
      in man occur over a time span of several decades. This combined with the
      prohibitive financial cost and ethical concerns to measure key metabolic
      parameters repeatedly in subjects for the major part of their life span makes
      that comprehensive longitudinal human data sets are virtually nonexistent. While
      experimental mice are often used, little is known whether this species is in fact
      an adequate model to better understand the mechanisms that drive the metabolic
      syndrome in man. We took up the challenge to study the response of male apoE*3
      Leiden.CETP mice (with a humanized lipid profile) to a high-fat high-cholesterol
      diet for 6 months. Study parameters include body weight, food intake, plasma and
      liver lipids, hepatic transcriptome, VLDL - triglyceride production and
      importantly the use of stable isotopes to measure hepatic de novo lipogenesis,
      gluconeogenesis, and biliary/fecal sterol secretion to assess metabolic fluxes.
      The key observations include (1) high inter-individual variation; (2) a largely
      unaffected hepatic transcriptome at 2, 3, and 6 months; (3) a biphasic response
      curve of the main metabolic features over time; and (4) maximum insulin
      resistance preceding dyslipidemia. The biphasic response in plasma triglyceride
      and total cholesterol appears to mimic that of men in cross-sectional studies.
      Combined, these observations suggest that studies such as these can help to
      delineate the causes of metabolic derangements in patients suffering from
      metabolic syndrome.

PMID- 29038352
TI  - Differential relationships of hepatic and epicardial fat to body composition in
      HIV.
AB  - HIV-infected patients commonly experience changes in central and peripheral fat
      content as well as ectopic fat accumulation. However, whether hepatic and
      epicardial fat stores relate differentially to body composition or how these
      associations are modified by HIV status has not been well explored. A previously
      recruited sample of 124 HIV-infected patients and 58 healthy controls had
      undergone dual energy X-ray absorptiometry (DEXA) and computed tomography (CT)
      from which body composition measures, liver-spleen ratio, and epicardial fat
      volume were obtained. Unique to the HIV-infected group, there was a parabolic
      association between abdominal subcutaneous adipose tissue (SAT) area and liver
      spleen ratio (P = 0.03, inflection point 324 cm2) such that hepatic fat content
      was greatest at the extremes of low and high SAT A quadratic model also closely
      described the relationship between mean leg fat and liver-spleen ratio among
      patients with HIV (P = 0.02, inflection point 4.7 kg), again suggesting greater
      liver fat content with both low and high leg fat. Notably, an analogous
      relationship of epicardial fat with SAT was not evident among HIV-infected
      individuals or healthy controls. In contrast, visceral adipose tissue (VAT)
      linearly related to both liver-spleen ratio in HIV and epicardial fat volume
      irrespective of HIV status in multivariable models. In conclusion, our analyses
      implicate both low and high SAT as risk factors for hepatic fat accumulation in
      HIV These findings add to growing evidence of SAT dysfunction in the setting of
      HIV infection, and highlight key physiologic differences between hepatic and
      epicardial fat depots.

PMID- 29038353
TI  - Cell cycle dependent expression of the CCK2 receptor by gastrointestinal
      myofibroblasts: putative role in determining cell migration.
AB  - The well-known action of the gastric hormone gastrin in stimulating gastric acid
      secretion is mediated by activation of cholecystokinin-2 receptors (CCK2R). The
      latter are expressed by a variety of cell types suggesting that gastrin is
      implicated in multiple functions. During wound healing in the stomach CCK2R may
      be expressed by myofibroblasts. We have now characterized CCK2R expression in
      cultured myofibroblasts. Immunocytochemistry showed that a relatively small
      proportion (1-6%) of myofibroblasts expressed the receptor regardless of the
      region of the gut from which they were derived, or whether from cancer or control
      tissue. Activation of CCK2R by human heptadecapeptide gastrin (hG17) increased
      intracellular calcium concentrations in a small subset of myofibroblasts
      indicating the presence of a functional receptor. Unexpectedly, we found over 80%
      of cells expressing CCK2R were also labeled with 5-ethynyl-2'-deoxyuridine (EdU)
      which is incorporated into DNA during S-phase of the cell cycle. hG17 did not
      stimulate EdU incorporation but increased migration of both EdU-labeled and
      unlabelled myofibroblasts; the migratory response was inhibited by a CCK2R
      antagonist and by an inhibitor of IGF receptor tyrosine kinase; hG17 also
      increased IGF-2 transcript abundance. The data suggest myofibroblasts express
      CCK2R in a restricted period of the cell cycle during S-phase, and that gastrin
      accelerates migration of these cells; it also stimulates migration of adjacent
      cells probably through paracrine release of IGF. Together with previous findings,
      the results raise the prospect that gastrin controls the position of dividing
      myofibroblasts which may be relevant in wound healing and cancer progression in
      the gastrointestinal tract.

PMID- 29038354
TI  - Association of urinary citrate excretion, pH, and net gastrointestinal alkali
      absorption with diet, diuretic use, and blood glucose concentration.
AB  - Urinary citrate (Ucit) protects against urinary stone formation. Acid base status
      and diet influence Ucit. However, the effect of demographics, diet, and glucose
      metabolism on Ucit excretion, urinary pH (U-pH) and net gastrointestinal alkali
      absorption (NAA) are not known. Twenty-four hour urine samples, blood glucose,
      creatinine, and cystatin C were obtained from non-Hispanic white sibships in
      Rochester, MN (n = 446; 64.5 +/- 9 years; 58% female). Diet was assessed by a
      food frequency questionnaire. The impact of blood glucose, demographics and
      dietary elements on Ucit excretion, U-pH, and NAA were evaluated in bivariate and
      multivariable models and interaction models that included age, sex, and weight.
      NAA significantly associated with Ucit and U-pH In multivariate models Ucit
      increased with age, weight, eGFRCys, and blood glucose, but decreased with loop
      diuretic and thiazide use. U-pH decreased with serum creatinine, blood glucose,
      and dietary protein but increased with dietary potassium. NAA was higher in males
      and increased with age, weight, eGFRCys and dietary potassium. Significant
      interactions were observed for Ucit excretion with age and blood glucose, weight
      and eGFRCys, and sex and thiazide use. Blood glucose had a significant and
      independent effect on U-pH and also Ucit. This study provides the first evidence
      that blood glucose could influence urinary stone risk independent of urinary pH,
      potentially providing new insight into the association of obesity and urinary
      stone disease.

PMID- 29038355
TI  - Isolated heart model demonstrates evidence of contractile and diastolic
      dysfunction in right ventricles from rats with sugen/hypoxia-induced pulmonary
      hypertension.
AB  - Although extensively used for the study of left ventricular function, limited
      experience exists with the isolated heart model in the evaluation of right
      ventricular (RV) function. In particular, no published experience exists with
      this tool in sugen/hypoxia-induced pulmonary hypertension (SuHx-PH), a frequently
      used model of severe and progressive PH We sought to characterize markers of RV
      contractile and diastolic function in SuHx-PH and to establish their relationship
      with markers of maladaptive RV remodeling. Hearts were excised from anesthetized
      Sprague Dawley rats with or without SuHx-PH and perfused via the aorta using a
      Langendorff preparation. We explored the Frank-Starling relationship of RV
      function (RV developed pressure, dP/dtmax, and dP/dtmin; all normalized to RV
      mass) by increasing RV end-diastolic pressure (RVEDP) from 0 to 40 mmHg.
      Functional studies were complemented by quantification of RV pro-apoptotic
      signaling (bcl2/bax), procontractile signaling (apelin), and stress response
      signaling (p38MAPK activation). Pearson's correlation analysis was performed for
      functional and biochemical parameters. SuHx-RVs exhibited severe RV dysfunction
      with marked hypertrophy and decreased echocardiographic cardiac output. For any
      given RVEDP, SuHx-RVs demonstrated less developed pressure and lower dP/dtmax, as
      well as less pronounced dP/dtmin, suggestive of decreased contractile and
      diastolic function. SuHx-RVs exhibited decreased bcl2/bax ratios, apelin
      expression, and p38MAPK activation. Bcl2/bax and apelin RNA abundance correlated
      positively with RV developed pressure and dP/dtmax and negatively with dP/dtmin
      p38MAPK activation correlated positively with RV developed pressure. We conclude
      that SuHx-RVs exhibit severe contractile and diastolic dysfunction. Increased pro
      apoptotic signaling and attenuated procontractile and stress response signaling
      may contribute to these functional alterations.

PMID- 29038356
TI  - Local production of neurostradiol affects gonadotropin-releasing hormone (GnRH)
      secretion at mid-gestation in Lagostomus maximus (Rodentia, Caviomorpha).
AB  - Females of the South American plains vizcacha, Lagostomus maximus, show peculiar
      reproductive features such as massive polyovulation up to 800 oocytes per estrous
      cycle and an ovulatory process around mid-gestation arising from the reactivation
      of the hypothalamic-hypophyseal-ovary (H.H.O.) axis. Estradiol (E2) regulates
      gonadotropin-releasing hormone (GnRH) expression. Biosynthesis of estrogens
      results from the aromatization of androgens by aromatase, which mainly occurs in
      the gonads, but has also been described in the hypothalamus. The recently
      described correlation between GnRH and ERalpha expression patterns in the
      hypothalamus of the vizcacha during pregnancy, with coexpression in the same
      neurons of the medial preoptic area, suggests that hypothalamic synthesis of E2
      may affect GnRH neurons and contribute with systemic E2 to modulate GnRH delivery
      during the gestation. To elucidate this hypothesis, hypothalamic expression and
      the action of aromatase on GnRH release were evaluated in female vizcachas
      throughout pregnancy. Aromatase and GnRH expression was increased significantly
      in mid-pregnant and term-pregnant vizcachas compared to early-pregnant and
      nonpregnant females. In addition, aromatase and GnRH were colocalized in neurons
      of the medial preoptic area of the hypothalamus throughout gestation. The
      blockage of the negative feedback of E2 induced by the inhibition of aromatase
      resulted in a significant increment of GnRH-secreted mass by hypothalamic
      explants. E2 produced in the same neurons as GnRH may drive intracellular E2 to
      higher levels than those obtained from systemic circulation alone. This may
      trigger for a prompt GnRH availability enabling H.H.O. activity at mid-gestation
      with ovulation and formation of accessory corpora lutea with steroidogenic
      activity that produce the necessary progesterone to maintain gestation to term
      and guarantee the reproductive success.

PMID- 29038357
TI  - Exposure to electronic cigarette vapors affects pulmonary and systemic expression
      of circadian molecular clock genes.
AB  - E-cigarette use has exploded in the past years, especially among young adults and
      smokers desiring to quit. While concerns are mostly based on the presence of
      nicotine and flavors, pulmonary effects of propylene glycol and glycerol
      inhalation, the main solvents of e-liquid have not been thoroughly investigated.
      In this preclinical study, mice were exposed 2 h daily for up to 8 weeks to
      vapors of propylene glycol and/or glycerol generated by an e-cigarette. Lung
      transcriptome analysis revealed it affected the expression level of genes of the
      circadian molecular clock, despite causing no inflammatory response. Periodical
      sacrifices showed that the rhythmicity of these regulatory genes was indeed
      altered in the lungs, but also in the liver, kidney, skeletal muscle, and brain.
      E-cigarette exposure also altered the expression of rhythmic genes (i.e., hspa1a
      and hspa1b), suggesting that alterations to the 'clock genes' could translate
      into systemic biological alterations. This study reveals that the major solvents
      used in e-cigarettes propylene glycol and glycerol, not nicotine or flavors, have
      unsuspected effects on gene expression of the molecular clock that are to be
      taken seriously, especially considering the fundamental role of the circadian
      rhythm in health and disease.

PMID- 29038358
TI  - Expression of genes involved in carbohydrate-lipid metabolism in muscle and fat
      tissues in the initial stage of adult-age obesity in fed and fasted mice.
AB  - C57Bl mice exhibit impaired glucose metabolism by the late adult age under
      standard living conditions. The aim of this study was to evaluate white adipose
      tissue (WAT), brown adipose tissue (BAT), and skeletal muscle expression of genes
      involved in carbohydrate-lipid metabolism at postpubertal stages preceding the
      late adult age in C57Bl mice. Muscle mRNA levels of uncoupling protein 3 (Ucp3)
      and carnitine palmitoyltransferase 1 (Cpt1) (indicators of FFA oxidation), WAT
      mRNA levels of hormone-sensitive lipase (Lipe) and lipoprotein lipase (Lpl)
      (indicators of lipolysis and lipogenesis), muscle and WAT mRNA levels of the type
      4 glucose transporter Slc2a4 (indicators of insulin-dependent glucose uptake),
      and BAT mRNA levels of uncoupling protein 1 (Ucp1) (indicator of thermogenesis)
      were measured in fed and 16 h-fasted mice in three age groups: 10-week-old
      (young), 15-week-old (early adult), and 30-week-old (late adult). Weight gain
      from young to early adult age was not accompanied by changes in WAT and BAT
      indexes and biochemical blood parameters. Weight gain from early to late adult
      age was accompanied by increased WAT and BAT indexes and decreased glucose
      tolerance. Muscle Ucp3 and Cpt1 mRNA levels and WAT Lipe and Slc2a4 mRNA levels
      increased from young to early adult age and then sharply decreased by the late
      adult age. Moreover, BAT Ucp1 mRNA level decreased in the late adult age. Fasting
      failed to increase muscle Cpt1 mRNA levels in late adult mice. These
      transcriptional changes could contribute to impaired glucose metabolism and the
      onset of obesity in late adult mice during normal development.

PMID- 29038359
TI  - Hyperoxia reduces insulin release and induces mitochondrial dysfunction with
      possible implications for hyperoxic treatment of neonates.
AB  - We previously showed that hyperoxia in vitro negatively affects beta cells of the
      rat. Here, we tested for possible clinical significance as well as mitochondrial
      interactions by hyperoxia, using human islets (function and viability), INS-1
      832/13 cells (mitochondrial metabolism), and mouse neonates (effects in vivo).
      Lastly, we assessed relevant parameters in a cohort of individuals born preterm
      and then exposed to hyperoxia. Human islets and INS-1 832/13 cells were exposed
      to 24 h of hyperoxia (90-92% oxygen). Mouse neonates were subjected to 5 days of
      continuous hyperoxia. Individuals born preterm were evaluated in terms of glucose
      homeostasis and beta cell function by HbA1c and the HOMA2 formula. In human
      islets, hyperoxia significantly reduced glucose-stimulated insulin secretion by
      42.2 +/- 5.3% and viability assessed by MTT by 22.5 +/- 5.4%. Hyperoxia down
      regulated mitochondrial complex II by 21 +/- 5% and upregulated complex III by 26
      +/- 10.1% and complex IV by 37 +/- 10.6%. Partly similar effects on mitochondrial
      complexes were found in hyperoxia-exposed INS-1 832/13 cells. Exposure to
      hyperoxia swiftly reduced oxygen consumption in these cells and increased
      mitochondrial uncoupling. Hyperoxia transiently but significantly reduced insulin
      release in mouse neonates. Individuals born preterm displayed higher HbA1c versus
      controls, as well as insulin resistance. Thus, hyperoxia exerts negative effects
      in vitro on human beta cells and results indicate inhibitory effects on insulin
      secretion in vivo in mouse neonates. Negative effects may be lessened by the
      demonstrated swift and profound mitochondrial adaptability. Our findings open the
      possibility that hyperoxia could negatively affect beta cells of preterm human
      neonates.

PMID- 29038360
TI  - Carotid sinus hypersensitivity: block of the sternocleidomastoid muscle does not
      affect responses to carotid sinus massage in healthy young adults.
AB  - The arterial baroreflex is crucial for short-term blood pressure control -
      abnormal baroreflex function predisposes to syncope and falling. Hypersensitive
      responses to carotid baroreflex stimulation using carotid sinus massage (CSM) are
      common in older adults and may be associated with syncope. The pathophysiology of
      this hypersensitivity is unknown, but chronic denervation of the
      sternocleidomastoid muscles is common in elderly patients with carotid sinus
      hypersensitivity (CSH), and is proposed to interfere with normal integration of
      afferent firing from the carotid baroreceptors with proprioceptive feedback from
      the sternocleidomastoids, producing large responses to CSM. We hypothesized that
      simulation of sternocleidomastoid "denervation" using pharmacological blockade
      would increase cardiovascular responses to CSM. Thirteen participants received
      supine and tilted CSM prior to intramuscular injections (6-8 mL distributed over
      four sites) of 2% lidocaine hydrochloride, and 0.9% saline (placebo) in
      contralateral sternocleidomastoid muscles. Muscle activation was recorded with
      electromyography (EMG) during maximal unilateral sternocleidomastoid contraction
      both pre- and postinjection. Supine and tilted CSM were repeated following
      injections and responses compared to preinjection. Following lidocaine injection,
      the muscle activation fell to 23 +/- 0.04% of the preinjection value (P < 0.001),
      confirming neural block of the sternocleidomastoid muscles. Cardiac (RRI, RR
      interval), forearm vascular resistance (FVR), and systolic arterial pressure
      (SAP) responses to CSM did not increase after lidocaine injection in either
      supine or tilted positions (supine: DeltaRRI -72 +/- 31 ms, DeltaSAP +2 +/- 1
      mmHg, DeltaFVR +4 +/- 4%; tilted: DeltaRRI -20 +/- 13 ms, DeltaSAP +2 +/- 2 mmHg,
      DeltaFVR +2 +/- 4%; all P > 0.05). Neural block of the sternocleidomastoid
      muscles does not increase cardiovascular responses to CSM. The pathophysiology of
      CSH remains unknown.

PMID- 29038361
TI  - Tumor necrosis factor alpha decreases aquaporin 3 expression in intestinal
      epithelial cells through inhibition of constitutive transcription.
AB  - Inflammatory diseases of the gut are associated with altered electrolyte and
      water transport, leading to the development of diarrhea. Epithelially expressed
      aquaporins (AQPs) are downregulated in inflammation, although the mechanisms
      involved are not known. We hypothesized that AQP3 expression in intestinal
      epithelial cells is altered in intestinal inflammation and that these changes are
      driven by tumor necrosis factor (TNF) alpha Human colonic adenocarcinoma (HT-29)
      cells were treated with TNFalpha to investigate signaling mechanisms in vitro.
      AQP3 expression was assessed by real-time PCR and radiolabeled glycerol uptake,
      with select inhibitors and a luciferase reporter construct used to further
      elucidate intracellular signaling. AQP3 expression was downregulated in HT-29
      cells treated with TNFalpha Luciferase reporter construct experiments revealed
      that TNFalpha downregulated constitutive transcriptional activity of the AQP3
      promoter, and inhibition of MEK/ERK and nuclear factor kappaB (NF-kappaB)
      signaling prevented the decrease in AQP3 mRNA expression. Constitutive AQP3
      expression was suppressed by specificity protein (Sp) 3, and knockdown of this
      transcription factor bound to the AQP3 promoter was able to partially prevent the
      TNFalpha-induced downregulation of AQP3. TNFalpha signals through MEK/ERK and NF
      kappaB to enhance the negative transcriptional control of AQP3 expression exerted
      by Sp3. Similar mechanisms regulate numerous ion channels, suggesting a common
      mechanism by which both ion and water transport are altered in inflammation.

PMID- 29038362
TI  - Cdc42 activation couples fluid shear stress to apical endocytosis in proximal
      tubule cells.
AB  - Cells lining the kidney proximal tubule (PT) respond to acute changes in
      glomerular filtration rate and the accompanying fluid shear stress (FSS) to
      regulate reabsorption of ions, glucose, and other filtered molecules and maintain
      glomerulotubular balance. Recently, we discovered that exposure of PT cells to
      FSS also stimulates an increase in apical endocytic capacity (Raghavan et al.
      PNAS, 111:8506-8511, 2014). We found that FSS triggered an increase in
      intracellular Ca2+ concentration ([Ca2+]i) that required release of extracellular
      ATP and the presence of primary cilia. In this study, we elucidate steps
      downstream of the increase in [Ca2+]i that link FSS-induced calcium increase to
      increased apical endocytic capacity. Using an intramolecular FRET probe, we show
      that activation of Cdc42 is a necessary step in the FSS-stimulated apical
      endocytosis cascade. Cdc42 activation requires the primary cilia and the FSS
      mediated increase in [Ca2+]i Moreover, Cdc42 activity and FSS-stimulated
      endocytosis are coordinately modulated by activators and inhibitors of
      calmodulin. Together, these data suggest a mechanism by which PT cell exposure to
      FSS is translated into enhanced endocytic uptake of filtered molecules.

PMID- 29038363
TI  - Moderate exercise training does not prevent the reduction in myocardial L-type
      Ca2+ channels protein expression at obese rats.
AB  - Authors have showed that obesity implicates cardiac dysfunction associated with
      myocardial L-type calcium channels (LTCCs) activity impairments, as well as
      moderate exercise training (MET) seems to be an important therapeutic tool. We
      tested the hypothesis that MET promotes improvements on LTCCS activity and
      protein expression at obesity induced by unsaturated high-fat diets, which could
      represent a protective effects against development of cardiovascular damage. Male
      Wistar rats were randomized in control (C, n = 40), which received a standard
      diet and obese (Ob; n = 40), which received high-fat diet. After 20 weeks, the
      animals were assigned at four groups: control (C; n = 12); control submitted to
      exercise training (ET; n = 14); obese (Ob; n = 10); and obese submitted to
      exercise training (ObET; n = 11). ET (5 days/week during 12 weeks) began in the
      21th week and consisted of treadmill running that was progressively increased to
      reach 60 min. Final body weight (FBW), body fat (BF), adiposity index (AI),
      comorbidities, and hormones were evaluated. Cardiac remodeling was assessed by
      morphological and isolated papillary muscles function. LTCCs activity was
      determined using specific blocker, while protein expression of LTCCs was
      evaluated by Western blot. Unsaturated high-fat diet promoted obesity during all
      experimental protocol. MET controlled obesity process by decreasing of FBW, BF,
      and AI. Obesity implicated to LTCCs protein expression reduction and MET was not
      effective to prevent this condition. ET was efficient to promote several
      improvements to body composition and metabolic parameters; however, it was not
      able to prevent or reverse the downregulation of LTCCs protein expression at
      obese rats.

PMID- 29038364
TI  - Oral and intravenous pharmacokinetics of taurine in sprague-dawley rats: the
      influence of dose and the possible involvement of the proton-coupled amino acid
      transporter, PAT1, in oral taurine absorption.
AB  - Taurine is involved in various physiological processes, and one of the most
      abundant amino acids in human. The aim was to investigate the mechanism for
      intestinal absorption of taurine in vivo using also in vitro mechanistic studies.
      Taurine absorption was measured in male Sprague-Dawley rats at 10-997 mg/kg and 1
      30 mg/kg for oral and intravenous administration, respectively. Oral absorption
      was measured in the presence of substrates for the proton-coupled amino acid
      transporter, PAT1, that is, 200 mg/kg proline (Pro) and sarcosine (Sar), and in
      the presence of 2-Amino-2-norbornanecarboxylic acid (BCH) (200 mg/kg). BCH is not
      an inhibitor of PAT1 or the taurine transporter, TauT, hence it was included as a
      negative control. In vitro studies investigating the transport mechanism of
      taurine were conducted in human intestinal Caco-2 cells. The pharmacokinetic
      investigations showed that intestinal taurine absorption was not saturable at the
      investigated doses, but that the time (tmax) to reach the maximal plasma
      concentration (Cmax) increased with dose. Furthermore, Sar and Pro, but not BCH,
      decreased taurine Cmax In vitro it was clearly shown that PAT1 mediated the
      cellular uptake of taurine and thereby facilitated the transepithelial taurine
      transport, which could be inhibited by Pro and Sar, but not BCH In vivo and in
      vitro results suggest that taurine absorption from the intestine is caused by
      PAT1.

PMID- 29038365
TI  - Muscle ion transporters and antioxidative proteins have different adaptive
      potential in arm than in leg skeletal muscle with exercise training.
AB  - It was evaluated whether upper-body compared to lower-body musculature exhibits a
      different phenotype in relation to capacity for handling reactive oxygen species
      (ROS), H+, La-, Na+, K+ and also whether it differs in adaptive potential to
      exercise training. Eighty-three sedentary premenopausal women aged 45 +/- 6 years
      (mean +/- SD) were randomized into a high-intensity intermittent swimming group
      (HIS, n = 21), a moderate-intensity swimming group (MOS, n = 21), a soccer group
      (SOC, n = 21), or a control group (CON, n = 20). Intervention groups completed
      three weekly training sessions for 15 weeks, and pre- and postintervention
      biopsies were obtained from deltoideus and vastus lateralis muscle. Before
      training, monocarboxylate transporter 4 (MCT4), Na+/K+ pump alpha2, and
      superoxide dismutase 2 (SOD2) expressions were lower (P < 0.05) in m deltoideus
      than in m vastus lateralis, whereas deltoid had higher (P < 0.05) Na+/H+
      exchanger 1 (NHE1) expression. As a result of training, Na+/K+ pump alpha2
      isoform expression was elevated only in deltoideus muscle, while upregulation (P
      < 0.05) of the alpha1 and beta1 subunits, phospholemman (FXYD1), NHE1, and
      superoxide dismutase 1 expression occurred exclusively in vastus lateralis
      muscle. The increased (P < 0.05) expression of MCT4 and SOD2 in deltoid muscle
      after HIS and vastus lateralis muscle after SOC were similar. In conclusion, arm
      musculature displays lower basal ROS, La-, K+ handling capability but higher Na+
      dependent H+ extrusion capacity than leg musculature. Training-induced changes in
      the ion-transporting and antioxidant proteins clearly differed between muscle
      groups.

PMID- 29038367
TI  - A nonimmune function of T cells in promoting lung tumor progression.
AB  - The involvement of effector T cells and regulatory T (T reg) cells in opposing
      and promoting solid organ carcinogenesis, respectively, is viewed as a shifting
      balance between a breach versus establishment of tolerance to tumor or self
      antigens. We considered that tumor-associated T cells might promote malignancy
      via distinct mechanisms used by T cells in nonlymphoid organs to assist in their
      maintenance upon injury or stress. Recent studies suggest that T reg cells can
      participate in tissue repair in a manner separable from their immunosuppressive
      capacity. Using transplantable models of lung tumors in mice, we found that
      amphiregulin, a member of the epidermal growth factor family, was prominently up
      regulated in intratumoral T reg cells. Furthermore, T cell-restricted
      amphiregulin deficiency resulted in markedly delayed lung tumor progression. This
      observed deterrence in tumor progression was not associated with detectable
      changes in T cell immune responsiveness or T reg and effector T cell numbers.
      These observations suggest a novel "nonimmune" modality for intratumoral T reg
      and effector T cells in promoting tumor growth through the production of factors
      normally involved in tissue repair and maintenance.

PMID- 29038368
TI  - Swope Supernova Survey 2017a (SSS17a), the optical counterpart to a gravitational
      wave source.
AB  - On 17 August 2017, the Laser Interferometer Gravitational-Wave Observatory (LIGO)
      and the Virgo interferometer detected gravitational waves (GWs) emanating from a
      binary neutron star merger, GW170817. Nearly simultaneously, the Fermi and
      INTEGRAL (INTErnational Gamma-Ray Astrophysics Laboratory) telescopes detected a
      gamma-ray transient, GRB 170817A. At 10.9 hours after the GW trigger, we
      discovered a transient and fading optical source, Swope Supernova Survey 2017a
      (SSS17a), coincident with GW170817. SSS17a is located in NGC 4993, an S0 galaxy
      at a distance of 40 megaparsecs. The precise location of GW170817 provides an
      opportunity to probe the nature of these cataclysmic events by combining
      electromagnetic and GW observations.

PMID- 29038370
TI  - A cosmic multimessenger gold rush.

PMID- 29038369
TI  - Electromagnetic evidence that SSS17a is the result of a binary neutron star
      merger.
AB  - Eleven hours after the detection of gravitational wave source GW170817 by the
      Laser Interferometer Gravitational-Wave Observatory and Virgo Interferometers, an
      associated optical transient, SSS17a, was identified in the galaxy NGC 4993.
      Although the gravitational wave data indicate that GW170817 is consistent with
      the merger of two compact objects, the electromagnetic observations provide
      independent constraints on the nature of that system. We synthesize the optical
      to near-infrared photometry and spectroscopy of SSS17a collected by the One-Meter
      Two-Hemisphere collaboration, finding that SSS17a is unlike other known
      transients. The source is best described by theoretical models of a kilonova
      consisting of radioactive elements produced by rapid neutron capture (the r
      process). We conclude that SSS17a was the result of a binary neutron star merger,
      reinforcing the gravitational wave result.

PMID- 29038366
TI  - Specifically differentiated T cell subset promotes tumor immunity over fatal
      immunity.
AB  - Allogeneic immune cells, particularly T cells in donor grafts, recognize and
      eliminate leukemic cells via graft-versus-leukemia (GVL) reactivity, and transfer
      of these cells is often used for high-risk hematological malignancies, including
      acute myeloid leukemia. Unfortunately, these cells also attack host normal
      tissues through the often fatal graft-versus-host disease (GVHD). Full separation
      of GVL activity from GVHD has yet to be achieved. Here, we show that, in mice and
      humans, a population of interleukin-9 (IL-9)-producing T cells activated via the
      ST2-IL-33 pathway (T9IL-33 cells) increases GVL while decreasing GVHD through two
      opposing mechanisms: protection from fatal immunity by amphiregulin expression
      and augmentation of antileukemic activity compared with T9, T1, and unmanipulated
      T cells through CD8alpha expression. Thus, adoptive transfer of allogeneic T9IL
      33 cells offers an attractive approach for separating GVL activity from GVHD.

PMID- 29038371
TI  - Swift and NuSTAR observations of GW170817: Detection of a blue kilonova.
AB  - With the first direct detection of merging black holes in 2015, the era of
      gravitational wave (GW) astrophysics began. A complete picture of compact object
      mergers, however, requires the detection of an electromagnetic (EM) counterpart.
      We report ultraviolet (UV) and x-ray observations by Swift and the Nuclear
      Spectroscopic Telescope Array of the EM counterpart of the binary neutron star
      merger GW170817. The bright, rapidly fading UV emission indicates a high mass
      (~0.03 solar masses) wind-driven outflow with moderate electron fraction (Ye ~
      0.27). Combined with the x-ray limits, we favor an observer viewing angle of ~30
      degrees  away from the orbital rotation axis, which avoids both obscuration from
      the heaviest elements in the orbital plane and a direct view of any
      ultrarelativistic, highly collimated ejecta (a gamma-ray burst afterglow).

PMID- 29038372
TI  - A radio counterpart to a neutron star merger.
AB  - Gravitational waves have been detected from a binary neutron star merger event,
      GW170817. The detection of electromagnetic radiation from the same source has
      shown that the merger occurred in the outskirts of the galaxy NGC 4993, at a
      distance of 40 megaparsecs from Earth. We report the detection of a counterpart
      radio source that appears 16 days after the event, allowing us to diagnose the
      energetics and environment of the merger. The observed radio emission can be
      explained by either a collimated ultrarelativistic jet, viewed off-axis, or a
      cocoon of mildly relativistic ejecta. Within 100 days of the merger, the radio
      light curves will enable observers to distinguish between these models, and the
      angular velocity and geometry of the debris will be directly measurable by very
      long baseline interferometry.

PMID- 29038374
TI  - Early spectra of the gravitational wave source GW170817: Evolution of a neutron
      star merger.
AB  - On 17 August 2017, Swope Supernova Survey 2017a (SSS17a) was discovered as the
      optical counterpart of the binary neutron star gravitational wave event GW170817.
      We report time-series spectroscopy of SSS17a from 11.75 hours until 8.5 days
      after the merger. Over the first hour of observations, the ejecta rapidly
      expanded and cooled. Applying blackbody fits to the spectra, we measured the
      photosphere cooling from [Formula: see text] to [Formula: see text] kelvin, and
      determined a photospheric velocity of roughly 30% of the speed of light. The
      spectra of SSS17a began displaying broad features after 1.46 days and evolved
      qualitatively over each subsequent day, with distinct blue (early-time) and red
      (late-time) components. The late-time component is consistent with theoretical
      models of r-process-enriched neutron star ejecta, whereas the blue component
      requires high-velocity, lanthanide-free material.

PMID- 29038376
TI  - Development of cyanine probes with dinitrobenzene quencher for rapid fluorogenic
      protein labelling.
AB  - A multicolour protein labelling technique using a protein tag and fluorogenic
      probes is a powerful approach for spatio-temporal analyses of proteins in living
      cells. Since cyanine fluorophores have attractive properties for multicolour
      imaging of proteins, there is a huge demand to develop fluorogenic cyanine probes
      for specific protein labelling in living cells. Herein, we develop fluorogenic
      cyanine probes for labelling a protein tag by using a dinitrobenzene fluorescence
      quencher. The probes enhanced fluorescence intensity upon labelling reactions and
      emitted orange or far-red fluorescence. Intramolecular interactions between the
      cyanine fluorophores and the dinitrobenzene quencher led not only to fluorescence
      quenching of the probes in the free state but also to promotion of labelling
      reactions. Furthermore, the probes successfully imaged cell-surface proteins
      without a washing process. These findings offer valuable information on the
      design of fluorogenic cyanine probes and indicate that the probes are useful as
      novel live-cell imaging tools.This article is part of the themed issue
      'Challenges for chemistry in molecular imaging'.

PMID- 29038373
TI  - Illuminating gravitational waves: A concordant picture of photons from a neutron
      star merger.
AB  - Merging neutron stars offer an excellent laboratory for simultaneously studying
      strong-field gravity and matter in extreme environments. We establish the
      physical association of an electromagnetic counterpart (EM170817) with
      gravitational waves (GW170817) detected from merging neutron stars. By
      synthesizing a panchromatic data set, we demonstrate that merging neutron stars
      are a long-sought production site forging heavy elements by r-process
      nucleosynthesis. The weak gamma rays seen in EM170817 are dissimilar to classical
      short gamma-ray bursts with ultrarelativistic jets. Instead, we suggest that
      breakout of a wide-angle, mildly relativistic cocoon engulfing the jet explains
      the low-luminosity gamma rays, the high-luminosity ultraviolet-optical-infrared,
      and the delayed radio and x-ray emission. We posit that all neutron star mergers
      may lead to a wide-angle cocoon breakout, sometimes accompanied by a successful
      jet and sometimes by a choked jet.

PMID- 29038375
TI  - Light curves of the neutron star merger GW170817/SSS17a: Implications for r
      process nucleosynthesis.
AB  - On 17 August 2017, gravitational waves (GWs) were detected from a binary neutron
      star merger, GW170817, along with a coincident short gamma-ray burst, GRB
      170817A. An optical transient source, Swope Supernova Survey 17a (SSS17a), was
      subsequently identified as the counterpart of this event. We present ultraviolet,
      optical, and infrared light curves of SSS17a extending from 10.9 hours to 18 days
      postmerger. We constrain the radioactively powered transient resulting from the
      ejection of neutron-rich material. The fast rise of the light curves, subsequent
      decay, and rapid color evolution are consistent with multiple ejecta components
      of differing lanthanide abundance. The late-time light curve indicates that
      SSS17a produced at least ~0.05 solar masses of heavy elements, demonstrating that
      neutron star mergers play a role in rapid neutron capture (r-process)
      nucleosynthesis in the universe.

PMID- 29038378
TI  - Current status and future challenges for molecular imaging.
AB  - Molecular imaging (MI), used in its wider sense of biology at the molecular
      level, is a field that lies at the intersection of molecular biology and
      traditional medical imaging. As advances in medicine have exponentially expanded
      over the last few decades, so has our need to better understand the fundamental
      behaviour of living organisms in a non-invasive and timely manner. This
      commentary draws from topics the authors addressed in their presentations at the
      2017 Royal Society Meeting 'Challenges for chemistry in molecular imaging', as
      well as a discussion of where MI is today and where it is heading in the
      future.This article is part of the themed issue 'Challenges for chemistry in
      molecular imaging'.

PMID- 29038379
TI  - Challenges for chemistry in molecular imaging.

PMID- 29038377
TI  - Recent development of nanoparticles for molecular imaging.
AB  - Molecular imaging enables us to non-invasively visualize cellular functions and
      biological processes in living subjects, allowing accurate diagnosis of diseases
      at early stages. For successful molecular imaging, a suitable contrast agent with
      high sensitivity is required. To date, various nanoparticles have been developed
      as contrast agents for medical imaging modalities. In comparison with
      conventional probes, nanoparticles offer several advantages, including
      controllable physical properties, facile surface modification and long
      circulation time. In addition, they can be integrated with various combinations
      for multimodal imaging and therapy. In this opinion piece, we highlight recent
      advances and future perspectives of nanomaterials for molecular imaging.This
      article is part of the themed issue 'Challenges for chemistry in molecular
      imaging'.

PMID- 29038380
TI  - Integrating nanomedicine and imaging.
AB  - Biomedical engineering and its associated disciplines play a pivotal role in
      improving our understanding and management of disease. Motivated by past
      accomplishments, such as the clinical implementation of coronary stents,
      pacemakers or recent developments in antibody therapies, disease management now
      enters a new era in which precision imaging and nanotechnology-enabled
      therapeutics are maturing to clinical translation. Preclinical molecular imaging
      increasingly focuses on specific components of the immune system that drive
      disease progression and complications, allowing the in vivo study of potential
      therapeutic targets. The first multicentre trials highlight the potential of
      clinical multimodality imaging for more efficient drug development. In this
      perspective, the role of integrating engineering, nanotechnology, molecular
      imaging and immunology to yield precision medicine is discussed.This article is
      part of the themed issue 'Challenges for chemistry in molecular imaging'.

PMID- 29038381
TI  - Has molecular imaging delivered to drug development?
AB  - Pharmaceutical research and development requires a systematic interrogation of a
      candidate molecule through clinical studies. To ensure resources are spent on
      only the most promising molecules, early clinical studies must understand
      fundamental attributes of the drug candidate, including exposure at the target
      site, target binding and pharmacological response in disease. Molecular imaging
      has the potential to quantitatively characterize these properties in small,
      efficient clinical studies. Specific benefits of molecular imaging in this
      setting (compared to blood and tissue sampling) include non-invasiveness and the
      ability to survey the whole body temporally. These methods have been adopted
      primarily for neuroscience drug development, catalysed by the inability to access
      the brain compartment by other means. If we believe molecular imaging is a
      technology platform able to underpin clinical drug development, why is it not
      adopted further to enable earlier decisions? This article considers current drug
      development needs, progress towards integration of molecular imaging into
      studies, current impediments and proposed models to broaden use and increase
      impact.This article is part of the themed issue 'Challenges for chemistry in
      molecular imaging'.

PMID- 29038382
TI  - Protonation of carboxyl groups in EuDOTA-tetraamide complexes results in
      catalytic prototropic exchange and quenching of the CEST signal.
AB  - The CEST properties of EuDOTA-tetraamide complexes bearing pendant carboxylate
      and carboxyl ethyl esters were measured as a function of pH. The CEST signal from
      the Eu3+-bound water molecule decreased in intensity between pH 8.5 and 4.5 while
      the proton exchange rates (kex) increased over this same pH range. In comparison,
      the CEST signal in the corresponding carboxyl ester derivatives was nearly
      constant. Both observations are consistent with stepwise protonation of the four
      carboxylic acid groups over this same pH range. This indicates that negative
      charges on the carboxyl groups above pH 6 facilitate the formation of a strong
      hydrogen-bonding network in the coordination second sphere above the single Eu3+
      bound water molecule, thereby decreasing prototropic exchange of protons on the
      bound water molecule with bulk water protons. The percentage of square
      antiprismatic versus twisted square antiprism coordination isomers also decreased
      as the appended carboxylic acid groups were positioned further away from the
      amide. The net effect of lowering the pH was an overall increase in kex and a
      quenching of the CEST signal.This article is part of the themed issue 'Challenges
      for chemistry in molecular imaging'.

PMID- 29038384
TI  - Multimodal nanoparticle imaging agents: design and applications.
AB  - Molecular imaging, where the location of molecules or nanoscale constructs can be
      tracked in the body to report on disease or biochemical processes, is rapidly
      expanding to include combined modality or multimodal imaging. No single imaging
      technique can offer the optimum combination of properties (e.g. resolution,
      sensitivity, cost, availability). The rapid technological advances in hardware to
      scan patients, and software to process and fuse images, are pushing the
      boundaries of novel medical imaging approaches, and hand-in-hand with this is the
      requirement for advanced and specific multimodal imaging agents. These agents can
      be detected using a selection from radioisotope, magnetic resonance and optical
      imaging, among others. Nanoparticles offer great scope in this area as they lend
      themselves, via facile modification procedures, to act as multifunctional
      constructs. They have relevance as therapeutics and drug delivery agents that can
      be tracked by molecular imaging techniques with the particular development of
      applications in optically guided surgery and as radiosensitizers. There has been
      a huge amount of research work to produce nanoconstructs for imaging, and the
      parameters for successful clinical translation and validation of therapeutic
      applications are now becoming much better understood. It is an exciting time of
      progress for these agents as their potential is closer to being realized with
      translation into the clinic. The coming 5-10 years will be critical, as we will
      see if the predicted improvement in clinical outcomes becomes a reality. Some of
      the latest advances in combination modality agents are selected and the
      progression pathway to clinical trials analysed.This article is part of the
      themed issue 'Challenges for chemistry in molecular imaging'.

PMID- 29038383
TI  - Biological effects of MRI contrast agents: gadolinium retention, potential
      mechanisms and a role for phosphorus.
AB  - No discussion of challenges for chemistry in molecular imaging would be complete
      without addressing the elephant in the room-which is that the purest of chemical
      compounds needs to interact with a biological system in a manner that does not
      perturb normal biology while still providing efficacious feedback to assist in
      diagnosis of disease. In the past decade, magnetic resonance imaging (MRI) agents
      long considered inert have produced adverse effects in certain patient
      populations under certain treatment regimens. More recently, inert blood pool
      agents have been found to deposit in the brain. Release of free metal is often
      suspected as the culprit but that hypothesis has yet to be validated. In
      addition, even innocuous agents can cause painful side effects during injection
      in some patients. In this brief review, we summarize known biological effects for
      gadolinium- and iron-based MRI contrast agents, and discuss some of the potential
      mechanisms for the observed biological effects, including the potential role of
      phosphorus imbalance, related to kidney disease or cancer, in destabilizing
      gadolinium-based chelates and precipitating free gadolinium.This article is part
      of the themed issue 'Challenges for chemistry in molecular imaging'.

PMID- 29038385
TI  - Spectral unmixing techniques for optoacoustic imaging of tissue pathophysiology.
AB  - A key feature of optoacoustic imaging is the ability to illuminate tissue at
      multiple wavelengths and therefore record images with a spectral dimension. While
      optoacoustic images at single wavelengths reveal morphological features, in
      analogy to ultrasound imaging or X-ray imaging, spectral imaging concedes sensing
      of intrinsic chromophores and externally administered agents that can reveal
      physiological, cellular and subcellular functions. Nevertheless, identification
      of spectral moieties within images obtained at multiple wavelengths requires
      spectral unmixing techniques, which present a unique mathematical problem given
      the three-dimensional nature of the optoacoustic images. Herein we discuss
      progress with spectral unmixing techniques developed for multispectral
      optoacoustic tomography. We explain how different techniques are required for
      accurate sensing of intrinsic tissue chromophores such as oxygenated and
      deoxygenated haemoglobin versus extrinsically administered photo-absorbing agents
      and nanoparticles. Finally, we review recent developments that allow accurate
      quantification of blood oxygen saturation (sO2) by transforming and solving the
      sO2 estimation problem from the spatial to the spectral domain.This article is
      part of the themed issue 'Challenges for chemistry in molecular imaging'.

PMID- 29038386
TI  - Effect of Statins on Patients and Graft Survival in Kidney Transplant Recipients:
      a Survival Meta-analysis.
AB  - INTRODUCTION: Modifying cardiovascular risk factors is very important for the
      patients after kidney transplantation. Statins are a potentially beneficial
      intervention for kidney transplant patients, and the effect of statins on
      cardiovascular outcomes in patients with chronic kidney disease varies according
      to the stages. This systematic review summarizes the potential beneficial effects
      of statins on kidney allograft outcome. MATERIALS AND METHODS: A systematic
      review and meta-analysis was conducted by literature search using the PubMed,
      Science Direct, Scopus, ISI Web of Knowledge, and Google Scholar. Articles
      published after 2000 reporting hazard ratios (HRs) for the effect of statins on
      patient and graft survival of kidney transplant patients were included. RESULTS:
      Seven articles were included in the systematic review, involving 1870 kidney
      transplant patients that received statins and 3339 kidney transplant patients as
      the control group. Statins has no protective effect on transplant rejection,
      graft survival or patient survival after kidney transplantation. The effect of
      statins on graft survival, however, was significant when adjusted for factors
      such as age, sex, and serum creatinine level (HR, 0.80; 95% CI, 0.69 to 0.92; P =
      .003). Similarly, patient survival was significantly better with statin use
      (adjusted HR, 0.75; 95% CI, 0.63 to 0.88; P = .003). CONCLUSIONS: The present
      study may provide valuable information on the potential beneficial effects of
      statins in kidney allograft recipients. Meta-analysis showed that the use of
      statins correlated independently with improved patient and graft survival after
      kidney transplantation.

PMID- 29038387
TI  - Nephrotoxic Effect of Aspartame as an Artificial Sweetener: a Brief Review.
AB  - Aspartame is one of the most popular artificial sweeteners over the world.
      Although its consumption is considered to be safe in acceptable daily intake
      ranges which were set by the United States Food and Drugs Administration and
      other regulatory agencies, there are lots of controversies regarding its safety
      nowadays. Some of the recent experimental and epidemiological studies showed that
      consumption of aspartame may causes some adverse health effects including
      obesity, metabolic syndrome, and alteration in gut microbiota. Moreover, studies
      on the nephrotoxic effect of aspartame have increased. A search of several
      literature databases for publications on adverse effects of aspartame on the
      kidney function from 1980 to 2016 showed that long-term consumption of aspartame
      led to a dose-dependent increased production of free radicals in renal tissues as
      well as kidney injury, based on several studies on animals However, given the
      lack of clinical data in this area, it is difficult to make a definitive
      conclusion regarding nephrotoxic effect of aspartame. Overall, consumers should
      be aware of the potential side effects of aspartame and other artificial
      sweeteners. At present it may be recommended that only a minimal amount of them
      would be consumed.

PMID- 29038388
TI  - Uncommon Presentation of Primary Renal Lymphoma.

PMID- 29038389
TI  - Association of Glomerular Filtration Rate With Cardiometabolic Risk Factors in
      Iranian Adolescents: CASPIAN III Study.
AB  - INTRODUCTION: This study aimed to assess the association of glomerular filtration
      rate (GFR) with cardiometabolic risk factors in Iranian adolescents. MATERIALS
      AND METHODS: Data of the 3rd round of a school-based surveillance system entitled
      "Childhood and Adolescence Surveillance and PreventIon of Adult Non-communicable
      Disease (CASPIAN III)" study was used for this study. A sample of 367 adolescents
      aged between 10 and 18 years was randomly selected. Glomerular filtration rate
      was estimated using the original and the updated Schwartz equations. The
      association of GFR with anthropometric data, blood pressure, lipid profile, and
      blood glucose was assessed in boys and girls by age group. RESULTS: Of the
      participants, 50.4% were boys and 26.2% were from rural regions. In the age group
      of 14 to 18 years, the ratio of low- to high-density lipoprotein cholesterol was
      significantly lower in the girls than the boys (P < .001), and the girls had
      significantly higher triglyceride and FBG levels. Significant correlations were
      found between GFR and waist circumference (r = 0.150 and P = .009 with the
      original Schwartz; r = 0.190 and P < .001 with the updated Schwartz) and body
      mass index (r = 0.115 and P = .03 with the original Schwartz; r = 0.121 and P =
      .02 with the updated Schwartz).   Conclusions. The above findings showed that
      obese and overweight Iranian adolescents were more likely to have lower kidney
      function. Strategies to decline impaired kidney function may include prevention
      of obesity and central obesity in this population.

PMID- 29038390
TI  - Dietary Animal-derived L-Arginine Intakes and Risk of Chronic Kidney Disease: a 6
      year Follow-up of Tehran Lipid and Glucose Study.
AB  - INTRODUCTION: There is inconsistent evidence regarding the potential role of L
      arginine intake on kidney function. This study investigated the association of
      dietary L-arginine intake and the risk of chronic kidney disease (CKD) in adults.
      MATERIALS AND METHODS: We evaluated 1780 men and women participated in the Tehran
      Lipid and Glucose Study, followed for a median of 6.3 years. Dietary intakes of
      total L-arginine as well as animal- and plant-derived L-arginine were assessed
      using the validated semi-quantitative food frequency questionnaire, at baseline.
      Demographics, anthropometrics, and biochemical variables were evaluated at
      baseline and again after a 3-year and a 6-year follow-up. The incidence of CKD
      was assessed across tertiles of L-arginine and its categories using multivariable
      logistic regression models. RESULTS: The mean dietary intakes of total, plant
      derived, and animal-derived L-arginine were 4.1 +/- 1.5 g/d, 1.8 +/- 0.9 g/d, and
      2.1 +/- 0.8 g/d, respectively. In the fully-adjusted logistic regression model,
      the highest compared to the lowest intakes of animal-derived L-arginine (2.57 g/d
      versus 1.05 g/d) increased the risk of CKD (relative risk, 1.54; 95% confidence
      interval, 1.06 to 2.14, P = .02 for trend). Animal-derived L-arginine was
      negatively associated with changes of estimated glomerular filtration rate and
      creatinine clearance rate during the follow-up. There was no significant
      association between total or plant-derived L-arginine intakes and the risk of CKD
      after 6.3 years of follow-up. CONCLUSIONS: Our findings suggested an adverse
      effect of higher intakes of L-arginine from animal sources that could be a
      dietary risk factor for development of kidney disease.

PMID- 29038391
TI  - Embryohistiogenesis of Vascular Tufts of Glomeruli: a Possible Hypothesis.
AB  - INTRODUCTION: Embryogenesis of the kidney glomeruli, especially its vascular
      component, has not been well documented. Glomeruli capillary tuft is surrounded
      and enveloped by visceral epithelial cells, which is a unique portal system that
      connects afferent with efferent arteriole without interaction with venular
      circulation. We hypothesized that the portal system embryologically has developed
      by extension of the intima of afferent arteriole into the stroma of glomerulus.
      We also hypothesized that juxtaglomeruli apparatus was developed from remnants of
      smooth muscle cells of the media of afferent arteriole at the anastomosing site
      with the Bowman capsule entrance. MATERIALS AND METHODS: We studied 5 human fetal
      kidneys by hematoxylin-eosin, periodic acid-Schiff, and immunoperoxidase staining
      techniques. RESULTS: Hematoxylin-eosin staining of fetal kidney showed presence
      of erythrocytes in early vesicle form of glomeruli that was confirmed by
      immunohistochemical staining with CD31, smooth muscle actin, and CD34 markers.
      These stains showed extension of extraglomerular arterioles to the glomeruli.
      Periodic acid-Schiff staining showed also the continuity of the basement membrane
      in extraglomeruli and internal glomerular vascular tufts. CONCLUSIONS: This study
      shows that there is a relationship between the metanephric blast cells and major
      vessel critical for angiogenesis. When afferent arteriole come in contact with
      the immature glomeruli, its intima migrates into the glomerular tuft to form
      intraglomerular capillary system, while its smooth muscle remains at the entrance
      orifice and develops juxtaglomerular apparatus cells.

PMID- 29038392
TI  - Urine Vancomycin Level as a Method for Drug Monitoring in Patients With Normal
      and Decreased Kidney Function.
AB  - INTRODUCTION: Therapeutic drug monitoring of vancomycin is an important issue in
      clinical decision-making and dosage modifying, particularly among patients in
      critical conditions and decreased kidney function. Urine is typically readily
      available in hospitalized patients and therapeutic drug monitoring in urine may
      be a reliable and noninvasive procedure compared to frequent blood sampling. We
      aimed to determine and validate the diagnostic yield of vancomycin trough level
      in urine. MATERIALS AND METHODS: In a prospective study, 95 patients who were
      treated with vancomycin for any clinical condition were enrolled in this study.
      Patients were divided into 2 groups according to their glomerular filtration rate
      (greater than 80 mL/min/1.73 m2 versus 15 mL/min/1.73 m2 to 80 mL/min/1.73 m2).
      Vancomycin serum trough levels and simultaneous urine trough levels were detected
      by high-pressure liquid chromatography. RESULTS: The mean serum and urine trough
      levels of vancomycin were 13.13 +/- 1.34 mg/L and 7.79 +/- 1.23 mg/L,
      respectively. The serum and urine trough levels had a positive linear correlation
      (r = 0.38, P < .001), which was also significant in patients with normal kidney
      function (r = 0.43, P = .001). The estimated serum concentration was equal to
      urine vancomycin concentration plus 5.3 mg/L. CONCLUSIONS: Urine levels of
      vancomycin correlate with simultaneous serum levels and may consistently predict
      serum levels in patients with normal kidney function. Therefore, urine vancomycin
      monitoring might be used as a noninvasive alternative to blood sampling,
      particularly in patients with normal kidney function.

PMID- 29038393
TI  - Association of Body Mass Index, Waist Circumference, and Waist-Stature Ratio With
      Urine Composition in Patients With Urolithiasis.
AB  - INTRODUCTION: This study was aimed to evaluate the correlation of body mass index
      (BMI), waist circumference (WC), and waist-stature ratio (WSR) with urinary
      composition in urolithiasis patients. MATERIALS AND METHODS: Medical reports of
      1410 urolithiasis patients referred to a tertiary in Tehran, from 2010 to 2015,
      were reviewed. Collected data included WC, BMI, and WSR, 24-hour urine
      composition, and the first-morning urine pH. Urinary relative supersaturation of
      calcium oxalate, calcium phosphate, and uric acid were calculated. Linear
      correlation and logistic regression models were used for study analyses. RESULTS:
      A total of 511 records were reviewed. In the women, supersaturation of calcium
      oxalate significantly correlated with BMI, WC, and WSR. Supersaturation of uric
      acid significantly correlated with WC. Using regression analyses, BMI and WSR
      were associated with greater supersaturation of calcium oxalate abnormality,
      which persisted after adjustment for confounding factors (odds ratio, 1.080; 95%
      confidence interval, 1.001 to 1.166 for BMI; odds ratio, 1.053; 95% confidence
      interval, 1.001 to 1.108 for WSR). Larger WC accompanied abnormal values for
      supersaturation of calcium oxalate; however, the model was marginally significant
      (odds ratio, 1.032; 95% confidence interval, 1.000 to 1.065; P = .05) in
      multivariable analysis. In the men on the other hand, none of the obesity indexes
      were associated with the supersaturation measures. CONCLUSIONS: Although both
      obesity and abdominal obesity correlated with supersaturation of calcium oxalate,
      mostly by changes in urine volume and pH in women, none of those indexes showed
      significant correlation with urine composition in the men population of our
      study.

PMID- 29038394
TI  - Factors Associated With Lumbar and Femoral Bone Mineral Density in Kidney
      Transplants Candidates.
AB  - INTRODUCTION: Data on risk factors associated with low bone mineral density are
      limited in patients with end-stage renal disease. This study evaluated the
      factors deemed associated with lumbar and femoral Z and T scores. MATERIALS AND
      METHODS: Clinical and demographic data of 98 patients waiting for kidney
      transplantation were collected, as well as lumbar and femoral bone
      densitometries, before transplantation. Osteoporosis and osteopenia and factors
      associated with bone mineral density were assessed. RESULTS: According to the
      femoral T score, 38.8% (95% confidence interval [CI], 29.1% to 48.4%), 44.9% (95%
      CI, 35.1% to 54.7%), and 16.3% (95% CI, 9.0% to 23.6%) of the patients had normal
      bone density, osteopenia, and osteoporosis, respectively. According to the lumbar
      T score, 54.1% (95% CI, 44.2% to 63.9%), 33.7% (95% CI, 24.3% to 44.0%), and
      12.2% (95% CI, 5.8% to 18.7%) of the patients had normal density, osteopenia, and
      osteoporosis, respectively. Age, serum levels of creatinine and parathyroid
      hormone, and use of calcitriol and calcium carbonate were associated with femoral
      densitometry scores. Serum total protein level, Rh-negative status, and B blood
      type were associated with the lumbar scores. CONCLUSIONS: Parathyroid hormone
      contributed to bone loss in our kidney transplant candidates, and B and Rh
      negative blood types were associated with a higher risk of lumbar osteoporosis
      while total protein was negatively associated with the risk of bone loss.
      Calcitriol might improve femoral mineral density, but calcium carbonate was
      negatively associated with femoral bone density. Age and higher creatinine levels
      were associated with higher femoral bone densities.

PMID- 29038395
TI  - Acute Interstitial Nephritis Induced by Citrullus Colocynthis.
AB  - Acute interstitial nephritis (AIN) is known as a common cause of acute kidney
      injury, found in 15% to 27% of kidney biopsies. Drug-induced AIN is currently the
      most common cause of AIN. The most common medications causing AIN are antibiotics
      and nonsteroidal anti-inflammatory drugs. We describe a case of Citrullus
      colocynthis (herbal remedy for diabetes mellitus and weight reduction) that
      induced AIN. A 31-year-old woman with major thalassemia, diabetes mellitus, and
      hepatitis C infection was admitted because of flank pain and unexpected increase
      in serum creatinine level. She had been using Citrullus colocynthis for 3 months.
      Kidney biopsy results suggested AIN. She did not respond to steroid therapy and
      underwent hemodialysis. We suggest the use of Citrullus colocynthis as a herbal
      medicine with extreme caution.

PMID- 29038396
TI  - Multiple Myeloma in a Patient With Familial Mediterranean Fever.
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive disease
      characterized by recurrent episodes of painful inflammation in the abdomen,
      chest, or joints. The coexistence of multiple myeloma (MM) and FMF is an
      extremely rare event. Here, we report a case of FMF with concurrent MM. A 63-year
      old woman was diagnosed with FMF since 15 years earlier. She was admitted with a
      complaint of low back pain. Regarding the presence of back pain, anemia,
      hypercalcemia, and kidney failure, a diagnosis of MM was suspected. A skeletal
      survey showed punched-out lesions in the skull. Serum protein electrophoresis
      demonstrated an immunoglobulin G kappa monoclonal gammopathy, and bone marrow
      aspiration revealed 30% involvement by abnormally appearing plasma cells,
      suggestive of MM. Although the association between FMF and MM may be a mere
      coincidence, further studies are necessary to understand their concurrent
      development.

PMID- 29038397
TI  - Errata.

PMID- 29038398
TI  - Notice of Inadvertent Duplicate Publication and Retraction.

PMID- 29038400
TI  - [Surgical Treatment of T3 Lung Cancer with Invasion of Chest Wall and Other
      Adjacent Organs].
AB  - We conducted a retrospective investigation in patients who underwent surgery for
      T3 lung cancer with invasion of chest wall and other adjacent organs. Fifty
      patients who underwent surgery for T3 lung cancer with invasion of adjacent
      organs were investigated. The chest wall was the most frequently invaded organ,
      followed by the pericardium and mediastinal pleura. In cases of chest wall
      invasion, patients underwent en bloc resection and, when a complete resection was
      judged feasible, extrapleural resection. Six patients with superior sulcus tumor
      underwent surgery after preoperative treatment. The 5-year-survival was 55.7%. A
      significant difference in 5-year survival was observed between complete resection
      and incomplete resection in patients with lung cancer with chest wall invasion(
      p<0.047).

PMID- 29038399
TI  - [Surgical Resection for Locally Advanced Lung Cancer].
AB  - Lung cancer invading neighboring anatomical structures is categorized as T3 or T4
      and is regarded as locally advanced lung cancer. The 8th Edition Lung Cancer
      Stage Classification reclassified tumors 5~7 cm in size as T3 and tumors >7 cm or
      invading the diaphragm as T4. The purpose of this study was to evaluate the
      treatment results for resectable cT3-4N0-1M0 non-small cell lung cancer. From
      1985 to 2016, 138 patients were surgically treated in our hospital, and their
      median follow-up was 78 months. Overall, the 5-year survival was 50%. According
      to the cT factor, the 5-year survival was 60% in patients with 5~7 cm tumors, 35%
      in patients with >7 cm tumors, and 58% in the group with chest wall
      invasion;however, no patients with tumors invading the diaphragm, pericardium or
      great vessels survived 5 years postoperatively. Preoperative chemotherapy was
      given to 16 patients( 12%), and 6 of those patients received chemoradiotherapy;40
      patients (29%) received postoperative chemotherapy. All patients who received
      preoperative chemoradiotherapy followed by surgery had a complete resection and
      good pathological effects. While surgery alone is associated with an insufficient
      prognosis in patients with T3-T4 lung cancer, the addition of preoperative
      treatment is promising for improving survival.

PMID- 29038401
TI  - [Surgical Resection of T4 Category Lung Cancer].
AB  - Surgery still remains the main stream in the multimodality treatment for locally
      advanced lung cancer. On the other hand, more than 50% of non-small cell lung
      cancer are excluded for surgical indications, especially T4 category of lung
      cancer. In this study, we showed 5 year overall survival rate of both 50 clinical
      T4 cases and 30 pathological T4 cases are 35.6% and 41.9% respectively. Those
      could be compared with the non-surgical treatment results in the literature.
      Through this study and analysis of other reports, we might consider surgical
      indications for T4 category lung cancer are as follows;invasion to mediastinum,
      spine, trachea, carina and additional nodules in ipsilateral different lobes with
      N0-1 status(esophagus is not included in this study). For obtaining R0 resection
      to improve survival and reducing postoperative morbidity and mortality rate,
      prudent evaluations for patients' selection including pre-operative staging
      before surgery are mandatory.

PMID- 29038402
TI  - [Complete Surgical Resection for Lung Cancer Invading Anterior Apex after
      Preoperative Chemoradiotherapy Via Transmanubrial Approach and Anterolateral
      Thoracotomy].
AB  - Surgical resection plays an important role as a radical treatment for lung
      cancers. Many lung cancer patients are found in an advanced state and it is
      currently in a condition that can not be operated, and the prognosis is also bad.
      For locally advanced lung cancer, complete resection including surrounding organs
      is expected by performing chemoradiotherapy before surgery. We report a case of
      complete surgical resection for lung cancer invading anterior apex after
      preoperative chemoradiotherapy via transmanubrial approach and anterolateral
      thoracotomy.

PMID- 29038403
TI  - [Salvage Surgery for Residual and Recurred Tumor after Definitive
      Chemoradiotherapy].
AB  - BACKGROUND: Standard treatment for clinical N2-locally advanced lung cancer is
      definitive chemoradiotherapy (CRT). For local recurrence or residual tumor after
      definitive CRT, salvage surgery may have effective treatment option with
      relatively high operative risk. OBJECTIVE: To examine the prognosis and risk of
      salvage surgery. METHOD: In 2001 to 2016, postoperative complications, overall
      survival and relapse free survival rate were examined in 17 patients who
      underwent salvage surgery after definitive CRT for clinical N2 or more primary
      lung cancer. RESULT: Median observation period 26.4 months, male 15 female 2,
      average age 58.6 years. This was 0.6% of 2,630 anatomical resections during this
      period. Average dose of radiation was 63.5 Gy. Median period from initial
      treatment to surgery was 16.0 months.15 lobectomy and 2 pneumonectomy. Average
      operation time was 289 minutes;blood loss was 271 ml. Bronchial stump coverage
      was performed in all cases, using 10 pericardial fat, 5 omentum, 2 intercostal
      muscle. Median of postoperative hospital days was 10. There was no perioperative
      and in-hospital death, but complications occurred in 6 cases (35.3 %). For a
      prolonged air leakage and 2 anastomotic fistula, 3 reoperations were needed(
      17.6%). 5-year overall survival rate was 80.7%, and 5-year relapse free survival
      rate was 51.0%. CONCLUSION: Salvage surgery for clinical N2 lung cancer has a
      high frequency of postoperative complications and becomes a patient's burden.
      Salvage surgery seems to be meaningful, but physicians should have sufficient
      knowledge and experience in conducting this treatment approach.

PMID- 29038404
TI  - [Treatment Policy for Avoiding Pneumonectomy Regarding the Locally Advanced Lung
      Cancers].
AB  - The problem of pneumonectomy may result from an elimination of the extensive
      pulmonary vascular bed as a unit. Therefore this paper has indicated that 10
      cases with the locally advanced lung cancers had been treated with some
      parenchymal sparing procedures including chemotherapy in order to avoid
      pneumonectomy. Six cases with preoperative chemotherapy were performed sleeve
      lobectomy in 3 cases, tangential pulmonary artery(PA) resection in 2, and left
      atrium partial resection in 1. One case with irradiation in vain was done sleeve
      LLL+lS4+5segmentectomy. Three cases without pre-treatment were done tangential PA
      resection in 2 cases, sleeve lobectomy in 1. Outcome was that there were no
      perioperative mortality and 7 cases achieved long-term survival, however, 2 cases
      died of relapse, and one died of pneumonia. On surgical technique U-shape
      mattress interrupted suture for bronchoplasty and tangential PA resection were
      proved very useful procedures.

PMID- 29038405
TI  - [Our Experiences of Vertebrectomy for Lung Cancer Invading the Spine].
AB  - BACKGROUND: Surgery for lung cancer invading the spine remains challenging
      associated with high morbidity and mortality. We describe our surgical approach
      and assess the outcome of surgical treatment lung cancer invading the spine.
      METHODS: We retrospectively reviewed our recent experiences of lung cancer with
      vertebral invasion, in which we have performed total or partial vertebrectomy
      from 2011 through 2015. RESULTS: We experienced 8 patients who were treated with
      partial or total vertebrectomy for lung cancer. Vertebral invasion was evaluated
      by chest computed tomography (CT) and magnetic resonance imaging findings. N
      factors were estimated as cN0 in all patients based on chest CT and PET-CT
      findings. Two patients were treated by preoperative induction therapy. Total
      vertebrectomy was performed in 2 patients, hemivertebrectomy in 2 patients and
      transverse-process resection in 4 patients. In all 8 cases, complete resection
      was performed. Morbidity was 75% (6 patients) and no mortality occurred. Overall
      survival rate( 5 years) was 75%. CONCLUSION: Lung cancer surgery combined with
      vertebrectomy is highly aggressive suegery associated with high morbidity,
      however, this procedure is a promising treatment option for selected lung cancer
      patients, such as N0M0 disease with invasion to the spine.

PMID- 29038406
TI  - [Results of Partial Atrial Resection in Advanced Lung Cancer].
AB  - The present study analyzed double centers experiences with extended combined
      resection of the left atrium in patients with lung cancer. From January 1972 to
      May 2017, 32 patients underwent lung resection with partial resection of the left
      atrium for lung cancer. Of them,( median age 62 years, range 40 to 79 years), 25
      were men (78%) and 7 were women. Twenty-three pneumonectomies (72%)were
      performed, of which 19 (59%) were right sided. Dissection of the interatrial
      groove was completed in 4 patients( 36.3%). Extracorporeal circulation system was
      used in 4 patients( 12%). Pathological analysis of resected lymph nodes
      identified 6 patients (19%) with N0, 13 patients with N1 (40%) and 13 patients
      with N2( 40%). There were 17 squamous cell carcinomas( 53%), 8 adenocarcinomas(
      25%), 3 pleomorphic carcinomas, 1 large cell carcinoma, 1 mucoepidermoid
      carcinoma, adenosquamous cell carcinoma and 1 combined small cell carcinoma and
      adenocarcinoma. Two patients underwent induction chemotherapy and 26 patients(
      81.2%) underwent adjuvant treatment. With a median follow-up of 21.8 months
      (0~120), the 3 and 5-year survival rate after the surgical resection was 13.7%
      and 23.8 %. Since January 2000, 11 patients were operated, 3 and 5-year survival
      rate was 50.0 and 36.3%. Histological N0-1 was associated with better median
      overall survival(OS) compared with N2, with a corresponding 5-year OS rate of
      18.9 and 7.7%, respectively.

PMID- 29038407
TI  - [Technique to Reinforce Double-barreled Distal Aortic Anastomosis in the Repair
      of Aortic Dissection].
AB  - We describe a technique to reinforce a double-barreled aortic anastomosis in the
      repair of chronic aortic dissection. After distal aortic resection was carried
      out, an intimal flap was incised lineally 1 cm in width along with its margin.
      This intimal band was reapproximated to the adventitia which supported the false
      lumen. The wedge-shaped excision was made on the residual intimal flap to
      maintain blood flow to both the true and false lumens. Two felt strips were
      circumferentially placed inside and outside of the aortic edge, and the layers
      were sandwiched together with monofilament sutures. Finally, the prosthetic graft
      was anastomosed to the reinforced aortic stump with continuous suture. If the
      length of the intimal edge was shorter than that of the dissected adventitia, the
      intima was incised in a long, triangular shape from its base to form 2 ligulate
      flaps. The flaps were then slid together and attached to the corresponding
      adventitia, and the aortic stump was reinforced using the sandwich technique.
      This technique may be an effective and safe method for reinforcement of a double
      barreled aortic anastomosis in the repair of chronic aortic dissection.

PMID- 29038408
TI  - [Aortitis Syndrome Requiring Redo Bentall Procedure with Coronary Artery Bypass
      Grafting due to Graft Detachment;Report of a Case].
AB  - A 53-year-old woman was referred to us for reoperation of aortic root. Twenty
      three years ago, she was diagnosed with aortitis and suffered from annuloaortic
      ectasia, aortic regurgitation, severe stenosis of left carotid and subclavian
      arteries and occulusion of the main trunk of left coronary artery. The left
      coronary system was perfused by collateral arteries from right coronary artery.
      She had undergone original Bentall procedure( Cooley graft 26 mm+SJM valve 25 mm)
      with coronary artery bypass grafting (CABG)[saphenous vein graft (SVG)-left
      anterior descending artery (LAD)]. When she was 52 years old, she suffered from
      angina on efforts. Computed tomography and catheter angiocardiogram revealed
      pseudoaneurysm formation due to detachment of right coronary artery button and
      occulusion of SVG. We underwent redo aortic root replacement (Hemashield graft 26
      mm+On-X valve 23 mm) with redo CABG (SVG-LAD). Eight mm graft was interposed
      between composite valve graft and right coronary button. Postoperative course was
      uneventful. She was discharged from the hospital on the 17th day, and is now
      doing well without any symptoms.

PMID- 29038410
TI  - [Vacuum-assisted Closure for Mediastinitis Caused by Methicillin-resistant
      Staphylococcus aureus after Coronary Artery Bypass Grafting;Report of a Case].
AB  - A 78-year-old man underwent off-pump coronary artery bypass grafting in our
      hospital. Purulent discharge from a sternotomy wound appeared 8 days after the
      operation of sternal re-fixation for sternal fracture. Methicillin-resistant
      Staphylococcus aureus(MRSA) was identified by the culture of the wound exudate.
      He underwent a surgical revision with the removal of the sternal wires and
      necrotic tissues. After sufficient irrigation, vacuum-assisted closure therapy
      was adopted and finally the wound was naturally healed. Vacuum-assisted closure
      therapy was an effective treatment for MRSA mediastinitis after coronary artery
      bypass grafting.

PMID- 29038409
TI  - [Total Arch Replacement for Distal Arch Aneurysm with Isolated Left Vertebral
      Artery;Report of a Case].
AB  - We herein present a case of distal aortic arch aneurysm with an isolated left
      vertebral artery(LVA). In surgery, after establishing cardiopulmonary bypass, the
      LVA was anastomosed to the left common carotid artery (LCCA) while under moderate
      hypothermia. Selective cerebral perfusion (SCP) was then initiated by inserting
      catheters into the brachiocephalic artery( BCA), the LCCA and the left subclavian
      artery (LSA). The aorta was transected between the BCA and the LCCA, and an open
      stent graft was deployed into the descending aorta during circulatory arrest.
      After reconstructing the LSA, LCCA and BCA, the ascending aorta was replaced with
      a graft. The patient recovered well without any cerebral complications, and
      computed tomography confirmed the patency of the reconstructed LVA. Regarding the
      surgical treatment of an aortic arch aneurysm with an isolated LVA,
      reconstructing the isolated LVA before SCP makes the establishment of SCP
      straightforward, thereby helping protect the brain from ischemia.

PMID- 29038411
TI  - [Emergent Thoracic Endovascular Aortic Repair and Subxiphoid Pericardiotomy for
      Retrograde Type A Acute Aortic Dissection with Cardiac Tamponade;Report of a
      Case].
AB  - Type A acute aortic dissection has a high rate of mortality. Emergent surgical
      repair is the gold standard treatment, but some patients cannot tolerate the open
      surgery. Here, we report an 82-year-old patient with a history of cerebral
      infarction and cerebral bleeding who presented with a depressed level of
      consciousness and who was in a state of shock. A computed tomography (CT) scan
      showed cardiac tamponade associated with retrograde type A aortic
      dissection(RAAD), with a primary entry tear at a distal site of the left
      subclavian artery. We therefore performed emergent primary entry closure with
      stent grafting using the Conformable Gore Tag device and emergent drainage of the
      cardiac tamponade with subxiphoid pericardiotomy. Postoperative CT scan showed
      complete closure of the primary entry tear and a completely thrombosed false
      lumen. Primary entry closure with stent grafting could be an effective option for
      RAAD that meets anatomical criteria.

PMID- 29038413
TI  - Percutaneous Coronary Intervention for Coronary Bifurcation Lesions.
AB  - Percutaneous coronary intervention (PCI) of lesions at coronary bifurcations
      poses a technical challenge. Short-term complications, including periprocedural
      myocardial infarction, and long-term complications such as in-stent restenosis
      and stent thrombosis, are higher in patients with bifurcation lesions. Techniques
      for PCI of bifurcation lesions include stenting of the main branch alone, and the
      use of two or more stents to cover the main and side branches. Two- or three
      stent techniques include T-stenting, crush, culotte, simultaneous kissing stents,
      V-stenting, and Y-stenting. The goal of these techniques is to minimize areas of
      vessel that are not covered by stent. Dedicated bifurcation stents exist,
      including stents with apertures that allow standard stents to be placed within
      the aperture. Simultaneous kissing balloon angioplasty in the two branches should
      be performed to optimize angiographic results. Many studies exist comparing the
      different techniques; however, no consensus exists on the preferred method.

PMID- 29038412
TI  - [Effects of High-frequency Jet Ventilation on Respiratory Failure after Total
      Arch Replacement Due to Acute Aortic Dissection with Morbid Obesity;Report of a
      Case].
AB  - A 55-year-old morbidly obese woman [body mass index (BMI) 51.2] developed acute
      type A aortic dissection, and she also presented with significant hypoxemia and
      hypercapnia. She underwent a successful emergency total arch replacement, but
      severe hypoxemia persisted and Pao2/Fio2 lowered to 71.9 mmHg. We therefore
      applied high frequency jet ventilation (HFJV), which soon improved the hypoxemia
      without hemodynamic compromise. HFJV was discontinued three days later, when her
      Pao2/Fio2 improved to 170.0 mmHg. Weaning from the respirator was initiated on
      postoperative day 13. The patient was extubated on postoperative day 19 and was
      discharged on postoperative day 74 free from disabilities. HFJV may be effective
      for severe hypoxemia after cardiovascular surgery.

PMID- 29038414
TI  - Timing of Percutaneous Coronary Intervention and Therapeutic Hypothermia in
      Patients With ST-Elevation Myocardial Infarction and Out-of-hospital Cardiac
      Arrest.
AB  - The American College of Cardiology/American Heart Association guidelines include
      a Class 1 recommendation to initiate therapeutic hypothermia (TH) in comatose
      patients with out-of-hospital cardiac arrest (OHCA) with an initial shockable
      rhythm who have achieved return of spontaneous circulation. There is also a Class
      1 recommendation for immediate angiography in these patients whose initial
      electrocardiography shows ST-elevation myocardial infarction (STEMI). However,
      due to a lack of clinical trials evaluating these patients who have received both
      percutaneous coronary intervention (PCI) and TH, controversy remains regarding
      whether the two can be safely combined. Furthermore, in patients who receive TH
      and PCI, another question to address is which therapy to initiate first. This
      article focuses on how best to manage comatose OHCA survivors who have an initial
      shockable rhythm and STEMI.

PMID- 29038415
TI  - Two Perspectives of the Appropriate Use Criteria in Cardiology Practice:
      Advantageous and Useful or Limiting and Harmful?
AB  - The appropriate use criteria (AUC) has become an integral part of the
      cardiologist's daily practice and have evolved greatly since their inception over
      a decade ago. However, as health care costs continue to rise, the AUC has come to
      play an even more pivotal role in the way medicine-specifically cardiology-is
      practiced today. This editorial describes two opposing viewpoints commonly held
      by practicing clinicians of the AUC. Written from the perspective of two fellows
      in-training looking ahead at the challenges and opportunities of clinical
      practice (under the auspices of several experienced clinicians and leaders of the
      American College of Cardiology), this article provides a fresh perspective on the
      impact AUC has on our patients, clinicians, and the health care system.

PMID- 29038416
TI  - Cardiac Metastasis of Nonvisceral Soft-tissue Leiomyosarcoma.
AB  - Metastasis of a nonvisceral leiomyosarcoma to the heart is rare. We present the
      case of a man with a history of an upper extremity cancerous lesion that was
      completely resected with appropriate surveillance monitoring, which then
      metastasized to the heart 14 years later, presenting as superior vena cava
      syndrome. Full evaluation found no other metastatic lesions, including no
      residual sarcoma at the former primary site. We include transthoracic
      echocardiography and computed tomography images of unusual presentation of the
      large mass extending from the caudal superior vena cava to the right atrium and
      into the right ventricle across the tricuspid valve.

PMID- 29038417
TI  - Role of Exogenous Phosphocreatine in Chemotherapy-induced Cardiomyopathy.
AB  - The 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) regimen is widely
      used in the management of breast cancer. The common cardiotoxic effects of
      doxorubicin include congestive heart failure and left ventricular dysfunction,
      and those of cyclophosphamide include pericarditis, myocarditis, and congestive
      heart failure. It has been postulated that cardiotoxicity of 5-fluorouracil
      presents as coronary artery diseases (eg, angina). Cardiomyopathy is a common
      outcome following treatment with the FAC regimen. We report on a 52-year-old
      woman with cardiomyopathy following chemotherapy and radiation therapy. The
      patient did not respond well to b-blockers and angiotensin-converting enzyme
      inhibitors. After the addition of exogenous phosphocreatine, the patient's
      cardiac condition improved significantly.

PMID- 29038418
TI  - Two Reports of Quadricuspid Aortic Valve With Aortic Insufficiency.
AB  - We report two cases of a quadricuspid aortic valve with severe aortic
      incompetence. Both patients presented with dyspnea on exertion. Their physical
      examinations demonstrated wide pulse pressures with diastolic murmurs. Bedside
      transthoracic Doppler echocardiography revealed preserved left ventricular
      systolic function and possible quadricuspid aortic valve with severe aortic
      incompetence in both patients. We proceeded with transesophageal echocardiography
      that confirmed a quadricuspid aortic valve with severe aortic incompetence in
      both patients. Left ventricular systolic function was preserved in both cases.
      Both patients had a preoperative cardiac catheterization, which showed normal
      coronary arteries. They were referred to cardiothoracic surgery and underwent
      successful aortic valve replacement with bioprosthetic valves.

PMID- 29038419
TI  - Expression and Clinical Significance of Tissue Inhibitor of Metalloproteinases-1
      (TIMP-1) and a Disintegrin and Metalloproteinase with Thrombospondin Type 1 Motif
      1 (ADAMTS1) in Post-Kidney-Transplant Bladder Tumors.
AB  - BACKGROUND To investigate the expression and clinical significance of tissue
      inhibitor of metalloproteinases-1 (TIMP-1) and a disintegrin and
      metalloproteinase with thrombospondin type 1 motif 1 (ADAMTS1) in post-kidney
      transplant bladder tumors. MATERIAL AND METHODS A total of 27 patients with new
      bladder tumors occurring after surgical kidney transplants (the experimental
      group) and 56 patients with conventional new bladder tumors (the control group)
      were included in this study. All the patients were confirmed to have transitional
      cell carcinomas by postoperative pathological examination. Fifteen pairs of new
      bladder tumor specimens (from each of the 2 groups) were selected and subjected
      to whole-genome oligonucleotide microarray screening to determine the differences
      in gene expression profiles and analysis using the biomolecule annotation system.
      Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR),
      immunohistochemistry, and Western blot analysis were performed to determine and
      compare differences in the expression of TIMP-l and ADAMTS1 in the urothelial
      tumors of the 2 groups. RESULTS Analysis of co-differentially expressed genes
      showed 23 groups of pathways with significant differences (P<0.05) and included
      immunosuppression and tumor development and progression. TIMP-l expression was
      significantly higher in the experimental group than in the control group, whereas
      ADAMTS1 expression was significantly lower in the experimental group than in the
      control group (P<0.05). CONCLUSIONS Significant differences in gene expression
      profiles were observed between patients with post-kidney transplant bladder
      tumors and those with conventional bladder tumors, and the expression of TIMP-1
      and ADAMTS1 has important significance for the diagnosis of post-kidney
      transplant bladder tumors.

PMID- 29038420
TI  - Effects of Different Training Loads on Emotional State and mRNA and Protein
      Expressions of N-Methyl-D-Aspartate Receptor Subunits, Postsynaptic Density 95,
      and Kinesin Family Member 17 in Hippocampus of Rats.
AB  - BACKGROUND Emotional state can be affected by different training loads. The aim
      of this study was to explore the changes of rat emotional state, as well as the
      mRNA and protein expressions of N-methyl-D-aspartate receptors (NMDARs),
      postsynaptic density 95 (PSD-95), and kinesin family member 17 (KIF-17) in the
      hippocampus, by long-term moderate-intensity and high-intensity training models
      in rats. MATERIAL AND METHODS The exercise model of SD rats was set up by
      treadmill running of moderate and high intensities for 4 weeks. The rats in the
      moderate-intensity training group were given endurance training with increasing
      intensity, while rats in the high-intensity training group were given high-speed
      training, and those in the normal control group were also established. The body
      weights of rats were measured before and after exercise to determine weight
      reduction. Real-time PCR and Western blotting were used to detect the mRNA and
      protein expressions of NMDARs, PSD-95, and KIF-17 in hippocampus of rats under
      different training loads. RESULTS Compared with the control group, the rats in
      the moderate-intensity training group had better body condition and emotional
      state, while the rats in the high-intensity training group had poor body
      condition and emotional state. The mRNA and protein expression of PSD-95, KIF-17,
      and NMDARs in the moderate-intensity training group were significantly elevated
      (P<0.05) while those in the high-intensity training group were suppressed
      (P<0.05). CONCLUSIONS Different training loads have remarkable influences on the
      cognition, emotion, and mental status of rats, and can affect the mRNA and
      protein expressions of NMDARs, PSD-95, and KIF-17 in rats. Appropriate training
      loads alleviate hypoxia damage to the hippocampus, and also effectively improve
      hippocampus function.

PMID- 29038421
TI  - Stabilization of phosphofructokinase 1 platelet isoform by AKT promotes
      tumorigenesis.
AB  - Phosphofructokinase 1 (PFK1) plays a critical role in glycolysis; however, its
      role and regulation in tumorigenesis are not well understood. Here, we
      demonstrate that PFK1 platelet isoform (PFKP) is the predominant PFK1 isoform in
      human glioblastoma cells and its expression correlates with total PFK activity.
      We show that PFKP is overexpressed in human glioblastoma specimens due to an
      increased stability, which is induced by AKT activation resulting from
      phosphatase and tensin homologue (PTEN) loss and EGFR-dependent PI3K activation.
      AKT binds to and phosphorylates PFKP at S386, and this phosphorylation inhibits
      the binding of TRIM21 E3 ligase to PFKP and the subsequent TRIM21-mediated
      polyubiquitylation and degradation of PFKP. PFKP S386 phosphorylation increases
      PFKP expression and promotes aerobic glycolysis, cell proliferation, and brain
      tumor growth. In addition, S386 phosphorylation in human glioblastoma specimens
      positively correlates with PFKP expression, AKT S473 phosphorylation, and poor
      prognosis. These findings underscore the potential role and regulation of PFKP in
      human glioblastoma development.Phosphofructokinase 1 (PFK1) plays a critical role
      in glycolysis. Here the authors show that PFK1 platelet isoform is upregulated in
      Glioblastoma and is required for tumor growth mechanistically, such upregulation
      is due to an increased stability induced by AKT activation via phosphorylation on
      residue S386.

PMID- 29038422
TI  - TRIM29 promotes DNA virus infections by inhibiting innate immune response.
AB  - Many double-stranded DNA viruses, such as Epstein-Barr virus, can establish
      persistent infection, but the underlying virus-host interactions remain poorly
      understood. Here we report that in human airway epithelial cells Epstein-Barr
      virus induces TRIM29, a member of the TRIM family of proteins, to inhibit innate
      immune activation. Knockdown of TRIM29 in airway epithelial cells enhances type I
      interferon production, and in human nasopharyngeal carcinoma cells results in
      almost complete Epstein-Barr virus clearance. TRIM29 is also highly induced by
      cytosolic double-stranded DNA in myeloid dendritic cells. TRIM29 -/- mice have
      lower adenovirus titers in the lung, and are resistant to lethal herpes simplex
      virus-1 infection due to enhanced production of type I interferon.
      Mechanistically, TRIM29 induces K48-linked ubiquitination of Stimulator of
      interferon genes, a key adaptor in double-stranded DNA-sensing pathway, followed
      by its rapid degradation. These data demonstrate that Epstein-Barr virus and
      possible other double-stranded DNA viruses use TRIM29 to suppress local innate
      immunity, leading to the persistence of DNA virus infections.Proteins of the TRIM
      family have regulatory functions in immune signaling, often via ubiquitination of
      target proteins. Here, the authors show that TRIM29 is induced upon infection
      with DNA viruses, resulting in degradation of STING, decreased interferon
      signaling and increased pathogenicity in mice.

PMID- 29038423
TI  - Regulation of T cell alloimmunity by PI3Kgamma and PI3Kdelta.
AB  - Phosphatidylinositol-3-kinases (PI3K) gamma and delta are preferentially enriched
      in leukocytes, and defects in these signaling pathways have been shown to impair
      T cell activation. The effects of PI3Kgamma and PI3Kdelta on alloimmunity remain
      underexplored. Here, we show that both PI3Kgamma -/- and PI3Kdelta D910A/D910A
      mice receiving heart allografts have suppression of alloreactive T effector cells
      and delayed acute rejection. However, PI3Kdelta mutation also dampens regulatory
      T cells (Treg). After treatment with low dose CTLA4-Ig, PI3Kgamma -/- , but not
      PI3Kappadelta D910A/D910A , recipients exhibit indefinite prolongation of heart
      allograft survival. PI3Kdelta D910A/D910A Tregs have increased apoptosis and
      impaired survival. Selective inhibition of PI3Kgamma and PI3Kdelta (using
      PI3Kdelta and dual PI3Kgammadelta chemical inhibitors) shows that PI3Kgamma
      inhibition compensates for the negative effect of PI3Kdelta inhibition on long
      term allograft survival. These data serve as a basis for future PI3K-based immune
      therapies for transplantation.Phosphatidylinositol-3-kinases (PI3K) gamma and
      delta are key regulators of T cell signaling. Here the author show, using mouse
      heart allograft transplantation models, that PI3Kgamma or PI3Kdelta deficiency
      prolongs graft survival, but selective inhibition of PI3Kgamma or PI3Kdelta
      reveals alternative transplant survival outcomes post CTLA4-Ig treatment.

PMID- 29038424
TI  - Frequency-dependent selection in vaccine-associated pneumococcal population
      dynamics.
AB  - Many bacterial species are composed of multiple lineages distinguished by
      extensive variation in gene content. These often cocirculate in the same habitat,
      but the evolutionary and ecological processes that shape these complex
      populations are poorly understood. Addressing these questions is particularly
      important for Streptococcus pneumoniae, a nasopharyngeal commensal and
      respiratory pathogen, because the changes in population structure associated with
      the recent introduction of partial-coverage vaccines have substantially reduced
      pneumococcal disease. Here we show that pneumococcal lineages from multiple
      populations each have a distinct combination of intermediate-frequency genes.
      Functional analysis suggested that these loci may be subject to negative
      frequency-dependent selection (NFDS) through interactions with other bacteria,
      hosts or mobile elements. Correspondingly, these genes had similar frequencies in
      four populations with dissimilar lineage compositions. These frequencies were
      maintained following substantial alterations in lineage prevalences once
      vaccination programmes began. Fitting a multilocus NFDS model of post-vaccine
      population dynamics to three genomic datasets using Approximate Bayesian
      Computation generated reproducible estimates of the influence of NFDS on
      pneumococcal evolution, the strength of which varied between loci. Simulations
      replicated the stable frequency of lineages unperturbed by vaccination, patterns
      of serotype switching and clonal replacement. This framework highlights how
      bacterial ecology affects the impact of clinical interventions.

PMID- 29038425
TI  - MRE11 and EXO1 nucleases degrade reversed forks and elicit MUS81-dependent fork
      rescue in BRCA2-deficient cells.
AB  - The breast cancer susceptibility proteins BRCA1 and BRCA2 have emerged as key
      stabilizing factors for the maintenance of replication fork integrity following
      replication stress. In their absence, stalled replication forks are extensively
      degraded by the MRE11 nuclease, leading to chemotherapeutic sensitivity. Here we
      report that BRCA proteins prevent nucleolytic degradation by protecting
      replication forks that have undergone fork reversal upon drug treatment. The
      unprotected regressed arms of reversed forks are the entry point for MRE11 in
      BRCA-deficient cells. The CtIP protein initiates MRE11-dependent degradation,
      which is extended by the EXO1 nuclease. Next, we show that the initial limited
      resection of the regressed arms establishes the substrate for MUS81 in BRCA2
      deficient cells. In turn, MUS81 cleavage of regressed forks with a ssDNA tail
      promotes POLD3-dependent fork rescue. We propose that targeting this pathway may
      represent a new strategy to modulate BRCA2-deficient cancer cell response to
      chemotherapeutics that cause fork degradation.BRCA proteins have emerged as key
      stabilizing factors for the maintenance of replication forks following
      replication stress. Here the authors describe how reversed replication forks are
      degraded in the absence of BRCA2, and a MUS81 and POLD3-dependent mechanism of
      rescue following the withdrawal of genotoxic agent.

PMID- 29038426
TI  - Identification of catalytic sites in cobalt-nitrogen-carbon materials for the
      oxygen reduction reaction.
AB  - Single-atom catalysts with full utilization of metal centers can bridge the gap
      between molecular and solid-state catalysis. Metal-nitrogen-carbon materials
      prepared via pyrolysis are promising single-atom catalysts but often also
      comprise metallic particles. Here, we pyrolytically synthesize a Co-N-C material
      only comprising atomically dispersed cobalt ions and identify with X-ray
      absorption spectroscopy, magnetic susceptibility measurements and density
      functional theory the structure and electronic state of three porphyrinic
      moieties, CoN4C12, CoN3C10,porp and CoN2C5. The O2 electro-reduction and operando
      X-ray absorption response are measured in acidic medium on Co-N-C and compared to
      those of a Fe-N-C catalyst prepared similarly. We show that cobalt moieties are
      unmodified from 0.0 to 1.0 V versus a reversible hydrogen electrode, while Fe
      based moieties experience structural and electronic-state changes. On the basis
      of density functional theory analysis and established relationships between redox
      potential and O2-adsorption strength, we conclude that cobalt-based moieties bind
      O2 too weakly for efficient O2 reduction.Nitrogen-doped carbon materials with
      atomically dispersed iron or cobalt are promising for catalytic use. Here, the
      authors show that cobalt moieties have a higher redox potential, bind oxygen more
      weakly and are less active toward oxygen reduction than their iron counterpart,
      despite similar coordination.

PMID- 29038427
TI  - Improved electrochemical properties of morphology-controlled titania/titanate
      nanostructures prepared by in-situ hydrothermal surface modification of self
      source Ti substrate for high-performance supercapacitors.
AB  - ABSTARCT: Ti substrate surface is modified into two-dimensional (2D) TiO2
      nanoplatelet or one-dimensional (1D) nanorod/nanofiber (or a mixture of both)
      structure in a controlled manner via a simple KOH-based hydrothermal technique.
      Depending on the KOH concentration, different types of TiO2 nanostructures (2D
      platelets, 1D nanorods/nanofibers and a 2D+1D mixed sample) are fabricated
      directly onto the Ti substrate surface. The novelty of this technique is the in
      situ modification of the self-source Ti surface into titania nanostructures, and
      its direct use as the electrochemical microelectrode without any modifications.
      This leads to considerable improvement in the interfacial properties between
      metallic Ti and semiconducting TiO2. Since interfacial states/defects have
      profound effect on charge transport properties of electronic/electrochemical
      devices, therefore this near-defect-free interfacial property of Ti-TiO2
      microelectrode has shown high supercapacitive performances for superior charge
      storage devices. Additionally, by hydrothermally tuning the morphology of titania
      nanostructures, the electrochemical properties of the electrodes are also tuned.
      A Ti-TiO2 electrode comprising of a mixture of 2D-platelet+1D-nanorod structure
      reveals very high specific capacitance values (~7.4 mF.cm-2) due to the unique
      mixed morphology which manifests higher active sites (hence, higher utilization
      of the active materials) in terms of greater roughness at the 2D-platelet
      structures and higher surface-to-volume-ratio in the 1D-nanorod structures.

PMID- 29038428
TI  - Denervation-related alterations and biological activity of miRNAs contained in
      exosomes released by skeletal muscle fibers.
AB  - Exosomes are vesicles released by many eukaryotic cells; their cargo includes
      proteins, mRNA and microRNA (miR) that can be transferred to recipient cells and
      regulate cellular processes in an autocrine or paracrine manner. While cells of
      the myoblast lineage secrete exosomes, it is not known whether skeletal muscle
      fibers (myofibers) release exosomes. In this study, we found that cultured
      myofibers release nanovesicles that have bilamellar membranes and an average size
      of 60-130 nm, contain typical exosomal proteins and miRNAs and are taken up by
      C2C12 cells. miR-133a was found to be the most abundant myomiR in these vesicles
      while miR-720 was most enriched in exosomes compared to parent myofibers.
      Treatment of NIH 3T3 cells with myofiber-derived exosomes downregulated the miR
      133a targets proteins Smarcd1 and Runx2, confirming that these exosomes have
      biologically relevant effects on recipient cells. Denervation resulted in a
      marked increase in miR-206 and reduced expression of miRs 1, 133a, and 133b in
      myofiber-derived exosomes. These findings demonstrate that skeletal muscle fibers
      release exosomes which can exert biologically significant effects on recipient
      cells, and that pathological muscle conditions such as denervation induce
      alterations in exosomal miR profile which could influence responses to disease
      states through autocrine or paracrine mechanisms.

PMID- 29038429
TI  - One Dimensional Coordination Polymer of Zn(II) for Developing Multifunctional
      Nanoparticles.
AB  - A variety of nanoparticles (NPs) including Ag, Au, Pd, Cr and mixed Cu/Fe have
      been synthesized in a non-activated (without solvent removal) one dimensional
      coordination polymer (CP) of Zn(II) via two different mechanisms, acid formation
      and redox activity of the framework. Main driving force to grow these NPs within
      the cavities of CP is the presence of free oxygens of one of the monodentate
      carboxylate groups of BDC ligand. These free oxygens act as anchoring sites for
      the metal ions of the metal precursors. Chemical and physical characteristics of
      the NPs within the framework have been evaluated by the high resolution
      transmission electron microscopic (HRTEM) images. Excluding Ag(0) and Pd(0) other
      NPs are present as combinations of their elemental as well as oxide forms
      (Au/Au2O3, Cr/Cr2O3/CrO2 and Cu/Cu2O, Fe/FeO). Synthesized Ag NPs within the
      framework show remarkable antibacterial efficacy at extremely low concentrations.
      Ag, Au and Cu/Fe NPs show ferromagnetic properties within the framework at room
      temperature. This polymer has potential to sequester highly toxic Cr(VI) to non
      toxic Cr(0), Cr(III) and Cr(IV) species.

PMID- 29038431
TI  - High rates of organic carbon processing in the hyporheic zone of intermittent
      streams.
AB  - Organic carbon cycling is a fundamental process that underpins energy transfer
      through the biosphere. However, little is known about the rates of particulate
      organic carbon processing in the hyporheic zone of intermittent streams, which is
      often the only wetted environment remaining when surface flows cease. We used
      leaf litter and cotton decomposition assays, as well as rates of microbial
      respiration, to quantify rates of organic carbon processing in surface and
      hyporheic environments of intermittent and perennial streams under a range of
      substrate saturation conditions. Leaf litter processing was 48% greater, and
      cotton processing 124% greater, in the hyporheic zone compared to surface
      environments when calculated over multiple substrate saturation conditions.
      Processing was also greater in more saturated surface environments (i.e. pools).
      Further, rates of microbial respiration on incubated substrates in the hyporheic
      zone were similar to, or greater than, rates in surface environments. Our results
      highlight that intermittent streams are important locations for particulate
      organic carbon processing and that the hyporheic zone sustains this fundamental
      process even without surface flow. Not accounting for carbon processing in the
      hyporheic zone of intermittent streams may lead to an underestimation of its
      local ecological significance and collective contribution to landscape carbon
      processes.

PMID- 29038430
TI  - Two-dimensional metallic tantalum disulfide as a hydrogen evolution catalyst.
AB  - Two-dimensional metallic transition metal dichalcogenides are emerging as
      prototypes for uncovering fundamental physical phenomena, such as
      superconductivity and charge-density waves, as well as for engineering-related
      applications. However, the batch production of such envisioned transition metal
      dichalcogenides remains challenging, which has hindered the aforementioned
      explorations. Herein, we fabricate thickness-tunable tantalum disulfide flakes
      and centimetre-sized ultrathin films on an electrode material of gold foil via a
      facile chemical vapour deposition route. Through temperature-dependent Raman
      characterization, we observe the transition from nearly commensurate to
      commensurate charge-density wave phases with our ultrathin tantalum disulfide
      flakes. We have obtained high hydrogen evolution reaction efficiency with the as
      grown tantalum disulfide flakes directly synthesized on gold foils comparable to
      traditional platinum catalysts. This work could promote further efforts for
      exploring new efficient catalysts in the large materials family of metallic
      transition metal dichalcogenides, as well as exploiting their applications
      towards more versatile applications.Metallic transition metal dichalcogenides are
      important materials for catalysis, but scalable and controllable preparation
      methods are scarce. Here, the authors synthesize 2H-TaS2 as centimetre-scale
      films of tunable thickness and show they are an efficient catalyst for hydrogen
      evolution.

PMID- 29038432
TI  - Efficacy and safety for Apatinib treatment in advanced gastric cancer: a real
      world study.
AB  - Apatinib has been proved to be effective and safe among patients in gastric
      cancer in Phase II and III Trials. We aimed to evaluate its efficacy and safety
      in real world practice, and to explore factors associated with efficacy. Between
      January 2015 and February 2017, totally 36 patients with advanced gastric
      adenocarcinoma or adenocarcinoma of gastroesophageal junction (GEJ) were enrolled
      and followed up retrospectively after failing at least two lines of systemic
      therapy. The mPFS was 2.65 months (95%CI 1.66-3.54), and mOS was 5.8 months
      (95%CI 4.77-6.83). Two patients achieved partial response, and nineteen achieved
      stable disease. The disease control rate (DCR) was 58.3%, and objective response
      rate (ORR) was 5.6%. Common grade adverse events were hypertension (38.9%),
      proteinuria (36.1%), and neutropenia (33.3%). And the most common adverse events
      over grade 3 were hand-foot syndrome (8.3%), anemia (5.6%), and diarrhea (5.6%).
      No treatment-related death was documented during the drug administration.
      Exploratory analyses indicated patients treated with antiangiogenic therapy
      previously were more likely to benefit from apatinib.

PMID- 29038433
TI  - Phenotyping of autoreactive B cells with labeled nucleosomes in 56R transgenic
      mice.
AB  - The phenotypic characterization of self-reactive B cells producing autoantibodies
      is one of the challenges to get further insight in the physiopathology of
      autoimmune diseases. We took advantage of our previously developed flow cytometry
      method, using labeled nucleosomes, prominent autoantigens in systemic lupus
      erythematosus, to analyze the phenotype of self-reactive B cells in the anti-DNA
      B6.56R mouse model. We showed that splenic anti-nucleosome B cells express mostly
      kappa light chains and harbor a marginal zone phenotype. Moreover, these
      autoreactive B cells fail to acquire a germinal center phenotype and are less
      abundant in the transitional T3 compartment. In conclusion, the direct detection
      of autoreactive B cells helped determine their phenotypic characteristics and
      provided a more direct insight into the B cell tolerance process in B6.56R mice.
      This method constitutes an interesting new tool to study the mechanisms of B cell
      tolerance breakdown in B6.56R mice crossed with autoimmune prone models.

PMID- 29038435
TI  - Specificity of surface EMG recordings for gastrocnemius during upright standing.
AB  - The relatively large pick-up volume of surface electrodes has for long motivated
      the concern that muscles other than that of interest may contribute to surface
      electromyograms (EMGs). Recent findings suggest however the pick-up volume of
      surface electrodes may be smaller than previously appreciated, possibly leading
      to the detection of surface EMGs insensitive to muscle activity. Here we combined
      surface and intramuscular recordings to investigate how comparably action
      potentials from gastrocnemius and soleus are represented in surface EMGs detected
      with different inter-electrode distances. We computed the firing instants of
      motor units identified from intramuscular EMGs detected from gastrocnemius and
      soleus while five participants stood upright. We used these instants to trigger
      and average surface EMGs detected from multiple skin regions along gastrocnemius.
      Results from 66 motor units (whereof 31 from gastrocnemius) revealed the surface
      recorded amplitude of soleus action potentials was 6% of that of gastrocnemius
      and did not decrease for inter-electrode distances smaller than 4 cm.
      Gastrocnemius action potentials were more likely detected for greater inter
      electrode distances and their amplitude increased steeply up to 5 cm inter
      electrode distance. These results suggest that reducing inter-electrode distance
      excessively may result in the detection of surface EMGs insensitive to
      gastrocnemius activity without substantial attenuation of soleus crosstalk.

PMID- 29038434
TI  - Barley SIX-ROWED SPIKE3 encodes a putative Jumonji C-type H3K9me2/me3 demethylase
      that represses lateral spikelet fertility.
AB  - The barley inflorescence (spike) comprises a multi-noded central stalk (rachis)
      with tri-partite clusters of uni-floretted spikelets attached alternately along
      its length. Relative fertility of lateral spikelets within each cluster leads to
      spikes with two or six rows of grain, or an intermediate morphology.
      Understanding the mechanisms controlling this key developmental step could
      provide novel solutions to enhanced grain yield. Classical genetic studies
      identified five major SIX-ROWED SPIKE (VRS) genes, with four now known to encode
      transcription factors. Here we identify and characterise the remaining major VRS
      gene, VRS3, as encoding a putative Jumonji C-type H3K9me2/me3 demethylase, a
      regulator of chromatin state. Exploring the expression network modulated by VRS3
      reveals specific interactions, both with other VRS genes and genes involved in
      stress, hormone and sugar metabolism. We show that combining a vrs3 mutant allele
      with natural six-rowed alleles of VRS1 and VRS5 leads to increased lateral grain
      size and greater grain uniformity.The VRS genes of barley control the fertility
      of the lateral spikelets on the barley inflorescence. Here, Bull et al. show that
      VRS3 encodes a putative Jumonji C-type histone demethylase that regulates
      expression of other VRS genes, and genes involved in stress, hormone and sugar
      metabolism.

PMID- 29038436
TI  - Signatures of a time-reversal symmetric Weyl semimetal with only four Weyl
      points.
AB  - Through intense research on Weyl semimetals during the past few years, we have
      come to appreciate that typical Weyl semimetals host many Weyl points.
      Nonetheless, the minimum nonzero number of Weyl points allowed in a time-reversal
      invariant Weyl semimetal is four. Realizing such a system is of fundamental
      interest and may simplify transport experiments. Recently, it was predicted that
      TaIrTe4 realizes a minimal Weyl semimetal. However, the Weyl points and Fermi
      arcs live entirely above the Fermi level, making them inaccessible to
      conventional angle-resolved photoemission spectroscopy (ARPES). Here, we use pump
      probe ARPES to directly access the band structure above the Fermi level in
      TaIrTe4. We observe signatures of Weyl points and topological Fermi arcs.
      Combined with ab initio calculation, our results show that TaIrTe4 is a Weyl
      semimetal with the minimum number of four Weyl points. Our work provides a
      simpler platform for accessing exotic transport phenomena arising in Weyl
      semimetals.Weyl semimetals are interesting because they are characterized by
      topological invariants, but specific examples discovered to date tend to have
      complicated band structures with many Weyl points. Here, the authors show that
      TaIrTe4 has only four Weyl points, the minimal number required by time-reversal
      symmetry.

PMID- 29038437
TI  - SRVF, a novel herbal formula including Scrophulariae Radix and Viticis Fructus,
      disrupts focal adhesion and causes detachment-induced apoptosis in malignant
      cancer cells.
AB  - When cells lose adhesion, they undergo detachment-induced apoptosis, known as
      anoikis. In contrast, tumor cells acquire resistance to anoikis, enabling them to
      survive, even after separating from neighboring cells or the ECM. Therefore,
      agents that restore anoikis sensitivity may serve as anti-cancer candidates. In
      this study, we constructed a novel herbal formula, SRVF, which contains
      Scrophulariae Radix (SR) and Viticis Fructus (VF). SRVF rapidly decreased cell
      adhesion, altered the cell morphology to round, and induced cell death; however,
      SR, VF, or their co-treatment did not. SRVF arrested HT1080 cells in G2/M phase,
      increased the levels of pro-apoptotic proteins, and decreased the levels of anti
      apoptotic proteins. Furthermore, SRVF efficiently reduced cell-cell and cell-ECM
      interactions by disrupting the F-actin cytoskeleton and down-regulating the
      levels of focal adhesion-related proteins, suggesting that SRVF efficiently
      triggers detachment-induced apoptosis (i.e., anoikis) in malignant cancer cells.
      In xenograft mouse models, daily oral administration of 50 or 100 mg/kg SRVF
      retarded tumor growth in vivo, and repeated administration of SRVF did not cause
      systemic toxicity in normal mice. These data collectively indicate that SRVF
      induces cancer cell death by restoring anoikis sensitivity via disrupting focal
      adhesion. Therefore, SRVF may be a safe and potent anti-cancer herbal decoction.

PMID- 29038438
TI  - Haplotype analysis of XRCC2 gene polymorphisms and association with increased
      risk of head and neck cancer.
AB  - We aimed to investigate the effect of hotspot variations of XRCC2 gene on the
      risk of head and neck cancer (HNC) in 400 patients and 400 controls. Five
      polymorphisms of XRCC2 gene G4234C (rs3218384), G4088T (rs3218373), G3063A
      (rs2040639), R188H (rs3218536) and rs7802034 were analyzed using Allele- specific
      polymerase chain reaction (ARMS-PCR) followed by sequence analysis. For
      rs3218373, the GG genotype indicated a statistically significant 3-fold increased
      risk of HNC (P < 0.001) after multivariate adjustment. For rs7802034, the GG
      genotype suggested statistically significant 2-fold increased risk of HNC (P <
      0.001). For SNP of rs3218536, the AA genotype indicated a significant 3-fold
      increased risk of HNC (P < 0.001). Additionally, haplotype analysis revealed that
      TACAG, TGGAG, TACGG and TAGGA haplotypes of XRCC2 polymorphisms are associated
      with HNC risk. Two SNPs in XRCC2 (rs2040639 and rs3218384) were found increased
      in strong linkage disequilibrium. Furthermore, joint effect model showed 20 fold
      (OR = 19.89; 95% CI = 2.65-149.36, P = 0.003) increased HNC risk in patients
      carrying four homozygous risk alleles of selected polymorphisms. These results
      show that allele distributions and genotypes of XRCC2 SNPs are significantly
      associated with increased HNC risk and could be a genetic adjuster for the said
      disease.

PMID- 29038440
TI  - miR-29b regulates expression of collagens I and III in chondrogenically
      differentiating BMSC in an osteoarthritic environment.
AB  - Osteoarthritis (OA) is characterized by a slowly progressing, irreversible loss
      of articular cartilage. Tissue engineering approaches for cartilage regeneration
      include stem cell-based strategies but not much is known about their repair
      capacity in an OA microenvironment. The aim of the present study was to identify
      factors regulating collagen expression during chondrogenic differentiation of
      bone marrow-derived mesenchymal stem cells (BMSC) in an OA microenvironment.
      Coculture with OA cartilage induced miR-29b expression in BMSC which inhibited
      collagen I and III expression. Elevated miR-29b expression resulted in higher
      caspase 3/7 activity and promoted apoptosis of BMSC in part by directly
      inhibiting the anti-apoptotic proteins Bcl-2 and Mcl-1. Stimulation with IFN
      gamma induced miR-29b expression in BMSC. Our results suggest that miR-29b
      affects BMSC-based OA cartilage regeneration because expression of collagen III,
      mainly produced by undifferentiated BMSC, and collagen I, a marker for
      dedifferentiated chondrocytes, are inhibited by miR-29b thus influencing
      composition of the newly formed ECM. This might be critical to avoid formation of
      inferior fibrocartilage instead of hyaline cartilage. Furthermore, higher miR-29b
      expression promotes apoptosis either preventing excessive cell growth or reducing
      the number of BMSC undergoing chondrogenesis. Thus, miR-29b has both supportive
      but possibly also unfavourable effects on BMSC-based OA cartilage regeneration.

PMID- 29038442
TI  - Precise measurement of hyperfine structure in the 3S1/2 state of 7Li.
AB  - We report a precise measurement of hyperfine structure in the 3S1/2 state of the
      odd isotope of Li, namely 7Li. The state is excited from the ground 2S1/2 state
      (which has the same parity) using two single-photon transitions via the
      intermediate 2P3/2 state. The value of the hyperfine constant we measure is A =
      93.095(52) MHz, which resolves two discrepant values reported in the literature
      measured using other techniques. Our value is also consistent with theoretical
      calculations.

PMID- 29038439
TI  - Analysis of Nkx3.1:Cre-driven Erk5 deletion reveals a profound spinal deformity
      which is linked to increased osteoclast activity.
AB  - Extracellular signal-regulated protein kinase 5 (ERK5) has been implicated during
      development and carcinogenesis. Nkx3.1-mediated Cre expression is a useful
      strategy to genetically manipulate the mouse prostate. While grossly normal at
      birth, we observed an unexpected phenotype of spinal protrusion in
      Nkx3.1:Cre;Erk5 fl/fl (Erk5 fl/fl) mice by ~6-8 weeks of age. X-ray, histological
      and micro CT (uCT) analyses showed that 100% of male and female Erk5 fl/fl mice
      had a severely deformed curved thoracic spine, with an associated loss of
      trabecular bone volume. Although sex-specific differences were observed,
      histomorphometry measurements revealed that both bone resorption and bone
      formation parameters were increased in male Erk5 fl/fl mice compared to wild type
      (WT) littermates. Osteopenia occurs where the rate of bone resorption exceeds
      that of bone formation, so we investigated the role of the osteoclast
      compartment. We found that treatment of RANKL-stimulated primary bone marrow
      derived macrophage (BMDM) cultures with small molecule ERK5 pathway inhibitors
      increased osteoclast numbers. Furthermore, osteoclast numbers and expression of
      osteoclast marker genes were increased in parallel with reduced Erk5 expression
      in cultures generated from Erk5 fl/fl mice compared to WT mice. Collectively,
      these results reveal a novel role for Erk5 during bone maturation and homeostasis
      in vivo.

PMID- 29038441
TI  - Distinct mechanisms of acquisition of mcr-1 -bearing plasmid by Salmonella
      strains recovered from animals and food samples.
AB  - Since the report of its discovery in E. coli in late 2015, the plasmid-mediated
      colistin resistance gene, mcr-1, has been detected in various bacterial species
      in clinical setting and various environmental niches. However, the transmission
      mechanisms of this gene in Salmonella is less defined. In this study, we
      conducted a comprehensive study to characterize the genetic features of mcr-1
      positive Salmonella strains isolated from animals and foods. Our data revealed
      that Salmonella recovered from animals and food specimens exhibited highly
      different PFGE patterns, and acquired mcr-1-encoding plasmids via different
      mechanism. Plasmids harboring mcr-1 in Salmonella food isolates were all
      conjugative and similar as plasmids reported in other species of
      Enterobacteriaceae, whereas mcr-1-bearing plasmids from animal Salmonella
      isolates were not conjugative, and belonged to the IncHI2 type. The lack of a
      region carrying the tra genes was found to account for the inability to undergo
      conjugation for various sizes of IncHI2 plasmids harbored by animal strains.
      These data suggest that transmission of mcr-1-positive Salmonella from animal to
      food might not be a common event and food isolates may have acquired mcr-1
      bearing plasmids from other mcr-1-positive bacteria such as E. coli, which co
      exist in food samples.

PMID- 29038444
TI  - Structural basis for maintenance of bacterial outer membrane lipid asymmetry.
AB  - The Gram-negative bacterial outer membrane (OM) is a unique bilayer that forms an
      efficient permeation barrier to protect the cell from noxious compounds 1,2 . The
      defining characteristic of the OM is lipid asymmetry, with phospholipids
      comprising the inner leaflet and lipopolysaccharides comprising the outer leaflet
      1-3 . This asymmetry is maintained by the Mla pathway, a six-component system
      that is widespread in Gram-negative bacteria and is thought to mediate retrograde
      transport of misplaced phospholipids from the outer leaflet of the OM to the
      cytoplasmic membrane 4 . The OM lipoprotein MlaA performs the first step in this
      process via an unknown mechanism that does not require external energy input.
      Here we show, using X-ray crystallography, molecular dynamics simulations and in
      vitro and in vivo functional assays, that MlaA is a monomeric alpha-helical OM
      protein that functions as a phospholipid translocation channel, forming a ~20-A
      thick doughnut embedded in the inner leaflet of the OM with a central,
      amphipathic pore. This architecture prevents access of inner leaflet
      phospholipids to the pore, but allows outer leaflet phospholipids to bind to a
      pronounced ridge surrounding the channel, followed by diffusion towards the
      periplasmic space. Enterobacterial MlaA proteins form stable complexes with
      OmpF/C 5,6 , but the porins do not appear to play an active role in phospholipid
      transport. MlaA represents a lipid transport protein that selectively removes
      outer leaflet phospholipids to help maintain the essential barrier function of
      the bacterial OM.

PMID- 29038443
TI  - Phylogenetic analysis of the metazoan carotenoid oxygenase superfamily: a new
      ancestral gene assemblage of BCO-like (BCOL) proteins.
AB  - Here we describe a new family of carotenoid cleavage oxygenases (CCOs) in
      metazoans, the BCO2-like (BCOL) clade, which contains lancelet, nematode, and
      molluscan carotenoid oxygenase sequences. Phylogenetic analysis of CCOs in all
      kingdoms of life confirmed that the BCOL enzymes are an independent clade of
      ancient origin. One of the predicted lancelet BCOL proteins, cloned and analyzed
      for carotenoid cleavage activity in a bacterial carotenoid expression system, had
      activity similar to lancelet BCO2 proteins, although with a preference for cis
      isomers. Our docking predictions correlated well with the cis-favored activity.
      The extensive expansions of the new animal BCOL family in some species (e.g.,
      lancelet) suggests that the carotenoid cleavage oxygenase superfamily has evolved
      in the "extremely high turnover" fashion: numerous losses and duplications of
      this family are likely to reflect complex regulation processes during
      development, and interactions with the environment. These findings also serve to
      provide a rationale for the evolution of the BCO-related outlier RPE65 retinol
      isomerase, an enzyme that does not utilize carotenoids as substrate or perform
      double-bond cleavage.

PMID- 29038445
TI  - Facile Solution Synthesis of Tungsten Trioxide Doped with Nanocrystalline
      Molybdenum Trioxide for Electrochromic Devices.
AB  - A facile, highly efficient approach to obtain molybdenum trioxide (MoO3)-doped
      tungsten trioxide (WO3) is reported. An annealing process was used to transform
      ammonium tetrathiotungstate [(NH4)2WS4] to WO3 in the presence of oxygen.
      Ammonium tetrathiomolybdate [(NH4)2MoS4] was used as a dopant to improve the film
      for use in an electrochromic (EC) cell. (NH4)2MoS4 at different concentrations
      (10, 20, 30, and 40 mM) was added to the (NH4)2WS4 precursor by sonication and
      the samples were annealed at 500  degrees C in air. Raman, X-ray diffraction, and
      X-ray photoelectron spectroscopy measurements confirmed that the (NH4)2WS4
      precursor decomposed to WO3 and the (NH4)2MoS4-(NH4)2WS4 precursor was
      transformed to MoO3-doped WO3 after annealing at 500  degrees C. It is shown that
      the MoO3-doped WO3 film is more uniform and porous than pure WO3, confirming the
      doping quality and the privileges of the proposed method. The optimal MoO3-doped
      WO3 used as an EC layer exhibited a high coloration efficiency of 128.1 cm2/C,
      which is larger than that of pure WO3 (74.5 cm2/C). Therefore, MoO3-doped WO3
      synthesized by the reported method is a promising candidate for high-efficiency
      and low-cost smart windows.

PMID- 29038446
TI  - External Quality Assurance for Laboratory Identification and Capsular Typing of
      Streptococcus pneumoniae.
AB  - An external quality assessment (EQA) scheme for pneumococcal serotype
      identification has been performed over a period of 11 years, by a network of
      European pneumococcal reference laboratories. We report the results from the EQA,
      and present an assessment of the acceptability and utility of the EQA scheme.
      Reports from 22 EQA panels distributed in 2005-2016 were analysed. Each EQA panel
      consisted of seven isolates. A questionnaire including seven questions related to
      the acceptability and utility of the EQA scheme was distributed to all
      participating laboratories. Altogether, 154 pneumococcal isolates were tested. Of
      the 92 serologically distinct serotypes currently defined, 49 serotypes were
      included in the rounds. Discrepant results were observed in eight EQA rounds,
      involving 11 isolates (7.1%, 95% CI: 4% to 12%). All participating laboratories
      reported that the EQA scheme was useful for quality assurance purposes. Our
      results show that comparable serotyping data can be obtained in different
      laboratories. The EQA participation helps to keep the typing procedures at a high
      standard and provides data for accreditation purposes. The EQA is helpful when
      new technologies are introduced, and reveal limitations of both genotypic and
      phenotypic methods. Continuation of the presented EQA scheme is planned.

PMID- 29038447
TI  - Li2MnO3 domain size and current rate dependence on the electrochemical properties
      of 0.5Li2MnO3.0.5LiCoO2 cathode material.
AB  - Layered-layered composite oxides of the form xLi2MnO3.(1-x) LiMO2 (M = Mn, Co,
      Ni) have received much attention as candidate cathode materials for lithium ion
      batteries due to their high specific capacity (>250mAh/g) and wide operating
      voltage range of 2.0-4.8 V. However, the cathode materials of this class
      generally exhibit large capacity fade upon cycling and poor rate performance
      caused by structural transformations. Since electrochemical properties of the
      cathode materials are strongly dependent on their structural characteristics, the
      roles of these components in 0.5Li2MnO3.0.5LiCoO2 cathode material was the focus
      of this work. In this work, the influences of Li2MnO3 domain size and current
      rate on electrochemical properties of 0.5Li2MnO3.0.5LiCoO2 cathodes were studied.
      Experimental results obtained showed that a large domain size provided higher
      cycling stability. Furthermore, fast cycling rate was also found to help reduce
      possible structural changes from layered structure to spinel structure that takes
      place in continuous cycling.

PMID- 29038448
TI  - Structural evolution of tunneling oxide passivating contact upon thermal
      annealing.
AB  - We report on the structural evolution of tunneling oxide passivating contact
      (TOPCon) for high efficient solar cells upon thermal annealing. The evolution of
      doped hydrogenated amorphous silicon (a-Si:H) into polycrystalline-silicon (poly
      Si) by thermal annealing was accompanied with significant structural changes.
      Annealing at 600  degrees C for one minute introduced an increase in the implied
      open circuit voltage (Voc) due to the hydrogen motion, but the implied Voc
      decreased again at 600  degrees C for five minutes. At annealing temperature
      above 800  degrees C, a-Si:H crystallized and formed poly-Si and thickness of
      tunneling oxide slightly decreased. The thickness of the interface tunneling
      oxide gradually decreased and the pinholes are formed through the tunneling oxide
      at a higher annealing temperature up to 1000  degrees C, which introduced the
      deteriorated carrier selectivity of the TOPCon structure. Our results indicate a
      correlation between the structural evolution of the TOPCon passivating contact
      and its passivation property at different stages of structural transition from
      the a-Si:H to the poly-Si as well as changes in the thickness profile of the
      tunneling oxide upon thermal annealing. Our result suggests that there is an
      optimum thickness of the tunneling oxide for passivating electron contact, in a
      range between 1.2 to 1.5 nm.

PMID- 29038449
TI  - Encrypted Antimicrobial Peptides from Plant Proteins.
AB  - Examples of bioactive peptides derived from internal sequences of proteins are
      known for decades. The great majority of these findings appear to be fortuitous
      rather than the result of a deliberate and methodological-based enterprise. In
      the present work, we describe the identification and the biological activities of
      novel antimicrobial peptides unveiled as internal fragments of various plant
      proteins founded on our hypothesis-driven search strategy. All putative encrypted
      antimicrobial peptides were selected based upon their physicochemical properties
      that were iteratively selected by an in-house computer program named Kamal. The
      selected peptides were chemically synthesized and evaluated for their interaction
      with model membranes. Sixteen of these peptides showed antimicrobial activity
      against human and/or plant pathogens, some with a wide spectrum of activity
      presenting similar or superior inhibition efficacy when compared to classical
      antimicrobial peptides (AMPs). These original and previously unforeseen molecules
      constitute a broader and undisputable set of evidences produced by our group that
      illustrate how the intragenic concept is a workable reality and should be
      carefully explored not only for microbicidal agents but also for many other
      biological functions.

PMID- 29038450
TI  - Visuo-acoustic stimulation that helps you to relax: A virtual reality setup for
      patients in the intensive care unit.
AB  - After prolonged stay in an intensive care unit (ICU) patients often complain
      about cognitive impairments that affect health-related quality of life after
      discharge. The aim of this proof-of-concept study was to test the feasibility and
      effects of controlled visual and acoustic stimulation in a virtual reality (VR)
      setup in the ICU. The VR setup consisted of a head-mounted display in combination
      with an eye tracker and sensors to assess vital signs. The stimulation consisted
      of videos featuring natural scenes and was tested in 37 healthy participants in
      the ICU. The VR stimulation led to a reduction of heart rate (p = 0. 049) and
      blood pressure (p = 0.044). Fixation/saccade ratio (p < 0.001) was increased when
      a visual target was presented superimposed on the videos (reduced search
      activity), reflecting enhanced visual processing. Overall, the VR stimulation had
      a relaxing effect as shown in vital markers of physical stress and participants
      explored less when attending the target. Our study indicates that VR stimulation
      in ICU settings is feasible and beneficial for critically ill patients.

PMID- 29038451
TI  - TC-PTP regulates the IL-7 transcriptional response during murine early T cell
      development.
AB  - Cytokines play a critical role in directing the discrete and gradual
      transcriptional changes that define T cell development. The interleukin-7
      receptor (IL-7R), via its activation of the JAK-STAT pathway, promotes gene
      programs that change dynamically as cells progress through T cell
      differentiation. The molecular mechanism(s) directing differential gene
      expression downstream of the IL-7R are not fully elucidated. Here, we have
      identified T cell protein tyrosine phosphatase (TC-PTP), also known as PTPN2, as
      a negative regulator of IL-7R-STAT signaling in T cell progenitors, contributing
      to both the quantitative and qualitative nature of STAT-gene targeting. Novel
      genetic strategies used to modulate TC-PTP expression demonstrate that depletion
      of TC-PTP expression heightens the phosphorylation of STAT family members,
      causing aberrant expression of an interferon-response gene profile. Such
      molecular re-programming results in deregulation of early development checkpoints
      culminating in inefficient differentiation of CD4+CD8+ double positive cells. TC
      PTP is therefore shown to be required to safeguard the dynamic transcriptome
      necessary for efficient T cell differentiation.

PMID- 29038452
TI  - Involvement of Ubiquitin-Conjugating Enzyme (E2 Gene Family) in Ripening Process
      and Response to Cold and Heat Stress of Vitis vinifera.
AB  - Ubiquitin-conjugating (UBC) E2 enzyme plays crucial roles in plant growth and
      development. Limited information can describe the function of UBC enzyme E2 in
      grapes. A total of 43 UBC enzyme E2 genes with conserved UBC domain were
      identified in grapes. These genes were divided into five groups based on
      phylogenetic tree with tomatoes. Sequence analyses indicated that VvUBCs in the
      same group possessed similar gene structures and conserved motifs. Gene
      distribution in chromosomes was uneven, and gene duplication existed in 36
      VvUBCs. Transcriptome and qRT-PCR analysis indicated that most VvUBCs are
      involved in ripening and post-harvest stage, and feature functional roles in
      grape organs. According to the transcriptome and qRT-PCR results, seven and six
      VvUBCs in grape responded to cold and heat stress, respectively, whereas no
      remarkable VvUBCs change was noted under salt or water-deficit stress. This study
      provides new insights to physiological and developmental roles of these enzymes
      and regulation mechanism of E2 genes in grapes.

PMID- 29038453
TI  - Cryptogamic stem covers may contribute to nitrous oxide consumption by mature
      beech trees.
AB  - Naturally produced by microbial processes in soil, nitrous oxide (N2O) is an
      important greenhouse gas contributing to climate change. Accordingly, there is a
      need to accurately quantify the capability of forest ecosystems to exchange N2O
      with the atmosphere. While N2O emissions from soils have been well studied, trees
      have so far been overlooked in N2O inventories. Here, we show that stems of
      mature beech trees (Fagus sylvatica) may act as a substantial sink of N2O from
      the atmosphere under conditions of soils consuming N2O. Consistent consumption of
      N2O by all stems investigated (ranging between -2.4 and -3.8 ug m-2 h-1) is a
      novel finding in contrast to current studies presenting trees as N2O emitters. To
      understand these fluxes, N2O exchange of photoautotrophic organisms associated
      with beech bark (lichens, mosses and algae) was quantified under laboratory
      conditions. All these organisms were net N2O sinks at full rehydration and
      temperature of 25  degrees C. The consumption rates were comparable to stem
      consumption rates measured under field conditions. Cryptogamic stem covers could
      be a relevant sink of N2O in European beech forests.

PMID- 29038454
TI  - Importance of interlayer H bonding structure to the stability of layered
      minerals.
AB  - Layered (oxy) hydroxide minerals often possess out-of-plane hydrogen atoms that
      form hydrogen bonding networks which stabilize the layered structure. However,
      less is known about how the ordering of these bonds affects the structural
      stability and solubility of these minerals. Here, we report a new strategy that
      uses the focused electron beam to probe the effect of differences in hydrogen
      bonding networks on mineral solubility. In this regard, the dissolution behavior
      of boehmite (gamma-AlOOH) and gibbsite (gamma-Al(OH)3) were compared and
      contrasted in real time via liquid cell electron microscopy. Under identical such
      conditions, 2D-nanosheets of boehmite (gamma-AlOOH) exfoliated from the bulk and
      then rapidly dissolved, whereas gibbsite was stable. Further, substitution of
      only 1% Fe(III) for Al(III) in the structure of boehmite inhibited delamination
      and dissolution. Factors such as pH, radiolytic species, and knock on damage were
      systematically studied and eliminated as proximal causes for boehmite
      dissolution. Instead, the creation of electron/hole pairs was considered to be
      the mechanism that drove dissolution. The widely disparate behaviors of boehmite,
      gibbsite, and Fe-doped boehmite are discussed in the context of differences in
      the OH bond strengths, hydrogen bonding networks, and the presence or absence of
      electron/hole recombination centers.

PMID- 29038455
TI  - A comparative study of machine learning methods for time-to-event survival data
      for radiomics risk modelling.
AB  - : Radiomics applies machine learning algorithms to quantitative imaging data to
      characterise the tumour phenotype and predict clinical outcome. For the
      development of radiomics risk models, a variety of different algorithms is
      available and it is not clear which one gives optimal results. Therefore, we
      assessed the performance of 11 machine learning algorithms combined with 12
      feature selection methods by the concordance index (C-Index), to predict loco
      regional tumour control (LRC) and overall survival for patients with head and
      neck squamous cell carcinoma. The considered algorithms are able to deal with
      continuous time-to-event survival data. Feature selection and model building were
      performed on a multicentre cohort (213 patients) and validated using an
      independent cohort (80 patients). We found several combinations of machine
      learning algorithms and feature selection methods which achieve similar results,
      e.g. , MSR-RF: C-Index = 0.71 and BT-COX: C-Index = 0.70 in combination with
      Spearman feature selection. Using the best performing models, patients were
      stratified into groups of low and high risk of recurrence. Significant
      differences in LRC were obtained between both groups on the validation cohort.
      Based on the presented analysis, we identified a subset of algorithms which
      should be considered in future radiomics studies to develop stable and clinically
      relevant predictive models for time-to-event endpoints.

PMID- 29038456
TI  - Incomplete Ionization of a 110 meV Unintentional Donor in beta-Ga2O3 and its
      Effect on Power Devices.
AB  - Understanding the origin of unintentional doping in Ga2O3 is key to increasing
      breakdown voltages of Ga2O3 based power devices. Therefore, transport and
      capacitance spectroscopy studies have been performed to better understand the
      origin of unintentional doping in Ga2O3. Previously unobserved unintentional
      donors in commercially available [Formula: see text] Ga2O3 substrates have been
      electrically characterized via temperature dependent Hall effect measurements up
      to 1000 K and found to have a donor energy of 110 meV. The existence of the
      unintentional donor is confirmed by temperature dependent admittance
      spectroscopy, with an activation energy of 131 meV determined via that technique,
      in agreement with Hall effect measurements. With the concentration of this donor
      determined to be in the mid to high 1016 cm-3 range, elimination of this donor
      from the drift layer of Ga2O3 power electronics devices will be key to pushing
      the limits of device performance. Indeed, analytical assessment of the specific
      on-resistance (Ronsp) and breakdown voltage of Schottky diodes containing the 110
      meV donor indicates that incomplete ionization increases Ronsp and decreases
      breakdown voltage as compared to Ga2O3 Schottky diodes containing only the
      shallow donor. The reduced performance due to incomplete ionization occurs in
      addition to the usual tradeoff between Ronsp and breakdown voltage.

PMID- 29038457
TI  - Bacteriome genetic structures of urban deposits are indicative of their origin
      and impacted by chemical pollutants.
AB  - Urban activities generate surface deposits over impervious surfaces that can
      represent ecological and health hazards. Bacteriome genetic structures of
      deposits washed off during rainfall events, over an urban industrial watershed,
      were inferred from 16 S rRNA gene (rrs) sequences generated by high throughput
      sequencing. Deposits were sampled over a 4 year-period from a detention basin
      (DB). Major shifts, matching key management practices, in the structure of these
      urban bacteriomes, were recorded. Correlation analyses of rrs similarities
      between samples and their respective concentrations in chemical pollutants,
      markers of human fecal contaminations (HF183) and antimicrobial resistances
      (integrons), were performed. Harsher environmental constraints building up in the
      older deposits led to an increase number of rrs reads from extremophiles such as
      Acidibacter and Haliangium. Deposits accumulating in the decantation pit of the
      DB showed an increase in rrs reads from warm blooded intestinal tract bacteria
      such as Bacteroides and Prevotella. This enrichment matched higher concentrations
      of Bacteroides HF183 genotypes normally restricted to humans. Bacteriomes of
      urban deposits appeared good indicators of human-driven environmental changes.
      Their composition was found representative of their origin. Soil particles and
      rain appeared to be major contributors of the inferred bacterial taxa recovered
      from recent deposits.

PMID- 29038458
TI  - Observation of current-induced bulk magnetization in elemental tellurium.
AB  - The magnetoelectric effect in bulk matter is of growing interest both
      fundamentally and technologically. Since the beginning of the century, the
      magnetoelectric effect has been studied intensively in multiferroic materials.
      However, magnetoelectric phenomena in materials without any (anti-)ferroic order
      remain almost unexplored. Here we show the observation of a new class of bulk
      magnetoelectric effect, by revisiting elemental trigonal tellurium. We
      demonstrate that elemental tellurium, which is a nonmagnetic semiconductor,
      exhibits current-induced magnetization. This effect is attributed to spin
      splitting of the bulk band owing to the lack of inversion symmetry in trigonal
      tellurium. This finding highlights magnetoelectricity in bulk matter driven by
      moving electrons without any (anti-)ferroic order. Notably, current-induced
      magnetization generates a magnetic field that is not circular around but is
      parallel to the applied current; thus, this phenomenon opens a new area of
      magnetic field generation beyond Ampere's law that may lead to industrial
      applications.Electrical control of magnetic response in bulk material without
      electric or magnetic order is rare and potentially attractive for high efficient
      spintronics. Here, the authors report magnetization in elemental tellurium driven
      purely by current without any (anti-)ferroic order.

PMID- 29038459
TI  - Small-scale variation of ammonia oxidisers within intertidal sediments dominated
      by ammonia-oxidising bacteria Nitrosomonas sp. amoA genes and transcripts.
AB  - While numerous studies have investigated the abundance of ammonia oxidising
      bacteria and archaea (AOB/AOA) via the ammonia monooxygenase gene amoA, less is
      known about their small-scale variation and if amoA gene abundance equates to
      activity. Here we present a spatial and temporal study of ammonia oxidation in
      two small intertidal bays, Rusheen and Clew bay, Ireland. Potential Nitrification
      Rate (PNR) was ten-fold higher in Rusheen bay (Clew: 0.27 +/- SD 0.55; Rusheen:
      2.46 +/- SD 3.4 NO2- ug-1 g-1 day-1, P < 0.001) than in Clew bay but amoA gene
      abundances were similar between bays, and comparable to those in other coastal
      ecosystems. Within bays AOB genes increased towards the muddy sediments and were
      positively correlated with PNR and pH. Less spatial variation was observed in AOA
      abundances which nevertheless positively correlated with pH and temperature and
      negatively with salinity and ammonia. Transcriptionally active AOB and AOA were
      quantified from all sites in Rusheen bay, February 2014, following the general
      trends observed at DNA level. AOB phylotypes predominantly from the known
      Nitrosomonas group were distributed across the bay, while Nitrosomonas group B
      phylotypes were absent from low salinity sites. AOA genes and transcripts were
      primarily affiliated with Thaumarchaeota group I.1a.

PMID- 29038460
TI  - A novel immunohistochemical score to predict early mortality in acute myeloid
      leukemia patients based on indoleamine 2,3 dioxygenase expression.
AB  - Indoleamine 2,3 dioxygenase-1 (IDO-1) is an enzyme in the kynurenine pathway
      which augments tumor-induced immune tolerance. Previous studies in childhood
      acute myeloid leukemia (AML) have shown a negative correlation of IDO-1 mRNA
      expression with outcomes. The aim of our study was to develop a practical and
      objective immunohistochemical technique to quantify IDO-1 expression on
      diagnostic bone marrow biopsies of AML patients in order to facilitate its use in
      routine clinical practice. IDO-1 mRNA was extracted from diagnostic bone marrow
      specimens from 29 AML patients. IDO-1 protein expression was assessed in 40 cases
      via immunohistochemistry and quantified by a novel 'composite IDO-1 score'. In a
      univariate analysis, higher age (p = 0.0018), male gender (p = 0.019), high risk
      cytogenetics (p = 0.002), higher IDO-1 mRNA (p = 0.005), higher composite IDO-1
      score (p < 0.0001) and not undergoing allogeneic stem cell transplant (SCT, p =
      0.0005) predicted poor overall survival. In a multivariate model that included
      the aforementioned variables, higher composite IDO-1 score (p = 0.007) and not
      undergoing allogeneic SCT (p = 0.007) was found to significantly predict poor
      outcomes. Further, patients who failed induction had higher composite IDO-1 score
      (p = 0.01). In conclusion, 'composite IDO-1 score' is a prognostic tool that can
      help identify a certain subset of AML patients with 'early mortality'. This
      unique subset of patients can potentially benefit from specific IDO-1 inhibitor
      therapy, currently in clinical trials.

PMID- 29038461
TI  - The Bacteroidales produce an N-acylated derivative of glycine with both
      cholesterol-solubilising and hemolytic activity.
AB  - The contribution of the gut microbiota to the metabolism of cholesterol is not
      well understood. In this study, we identify 21 fosmid clones from a human gut
      microbiome metagenomic library that, when expressed in Escherichia coli, produce
      halos on LB agar supplemented with 0.01% (w/v) cholesterol (LBC agar). Analysis
      of 14 of these clones revealed that they all share a fragment of DNA with
      homology to the genome of Bacteroides vulgatus. The gene responsible for halo
      production on LBC agar, named choA, was identified as an N-acyltransferase known
      to produce an acylated glycine molecule called commendamide. In this study we
      show that commendamide is capable of producing a halo on LBC agar suggesting that
      this molecule is solubilizing the cholesterol micelles in LBC agar. We also show
      that commendamide is responsible for the previously described hemolytic activity
      associated with the choA orthologue in Bacteroides fragilis. A functional
      analysis of ChoA identified 2 amino acids that are important for commendamide
      biosynthesis and we present phylogenetic and functional data showing that
      orthologues of choA are found only in the order Bacteroidales. Therefore, the
      production of commendamide may be an adaptation to the environments colonized by
      the Bacteroidales, including the mammalian gut.

PMID- 29038462
TI  - Development of an athyroid mouse model using 131I ablation after preparation with
      a low-iodine diet.
AB  - We optimized the protocol for thyroid ablation in living mice using radioactive
      iodine (RAI) and a low-iodine diet (LID). To examine the effect of LID on thyroid
      ablation, mice were randomly divided into 4 groups: Vehicle, 131I 2.775 MBq, 131I
      5.55 MBq, and LID + 131I 2.775 MBq. The LID group was fed a LID for up to 7 days
      and then mice in the 131I 2.775, 131I 5.55, and LID + 131I 2.775 MBq groups were
      intravenously administrated with 131I, respectively. Scintigraphy imaging with
      99mTc pertechnetate was performed once in 2 weeks for 4 weeks. After
      establishment of athyroid mice, control or athyroid mice were injected with human
      anaplastic thyroid cancer cells co-expressing sodium iodine symporter and
      enhanced firefly luciferase (ARO/NF) to evaluate RAI uptake. Scintigraphy imaging
      with 99mTc pertechnetate was performed with ARO/NF tumor-bearing mice.
      Scintigraphy imaging showed decreased thyroid uptake in the LID + 131I 2.775 MBq
      group compared to other groups. Scintigraphy images showed that tumor uptake was
      statically higher in athyroid mice than in control mice. These data suggest that
      these optimized conditions for thyroid ablation could be helpful to establish an
      in vivo mouse model.

PMID- 29038464
TI  - Unveiling some FDA-approved drugs as inhibitors of the store-operated Ca2+ entry
      pathway.
AB  - The store-operated calcium entry (SOCE) pathway is an important route for
      generating cytosolic Ca2+ signals that regulate a diverse array of biological
      processes. Abnormal SOCE seem to underlie several diseases that notably include
      allergy, inflammation and cancer. Therefore, any modulator of this pathway is
      likely to have significant impact in cell biology under both normal and abnormal
      conditions. In this study, we screened the FDA-approved drug library for agents
      that share significant similarity in 3D shape and surface electrostatics with
      few, hitherto best known inhibitors of SOCE. This has led to the identification
      of five drugs that showed dose-dependent inhibition of SOCE in cell-based assay,
      probably through interacting with the Orai1 protein which effectively mediates
      SOCE. Of these drugs, leflunomide and teriflunomide could suppress SOCE
      significantly at clinically-relevant doses and this provides for an additional
      mechanism towards the therapeutic utility of these drugs as immunosuppressants.
      The other three drugs namely lansoprazole, tolvaptan and roflumilast, were less
      potent in suppressing SOCE but were more selective and thus they may serve as
      novel scaffolds for future development of new, more efficacious SOCE inhibitors.

PMID- 29038463
TI  - NCoR1 restrains thymic negative selection by repressing Bim expression to spare
      thymocytes undergoing positive selection.
AB  - Thymocytes must pass both positive and negative selections to become mature T
      cells. Negative selection purges thymocytes whose T-cell receptors (TCR) exhibit
      high affinity to self-peptide MHC complexes (self pMHC) to avoid autoimmune
      diseases, while positive selection ensures the survival and maturation of
      thymocytes whose TCRs display intermediate affinity to self pMHCs for effective
      immunity, but whether transcriptional regulation helps conserve positively
      selected thymocytes from being purged by negative selection remains unclear. Here
      we show that the specific deletion of nuclear receptor co-repressor 1 (NCoR1) in
      T cells causes excessive negative selection to reduce mature thymocyte numbers.
      Mechanistically, NCoR1 protects positively selected thymocytes from negative
      selection by suppressing Bim expression. Our study demonstrates a critical
      function of NCoR1 in coordinated positive and negative selections in the
      thymus.Thymocytes are screened by two processes, termed positive and negative
      selections, which are permissive only for immature thymocytes with intermediate
      avidity to the selecting ligands. Here the authors show that the nuclear receptor
      NCoR1 suppresses Bim1 to inhibit negative selection and promote thymocyte
      survival.

PMID- 29038465
TI  - NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and
      injury.
AB  - Damage-associated molecular patterns (DAMP) trigger innate immune response and
      exacerbate inflammation to combat infection and cellular damage. Identifying
      DAMPs and revealing their functions are thus of crucial importance. Here we
      report that two molecules, N-myc and STAT interactor (NMI) and interferon-induced
      protein 35 (IFP35) act as DAMPs and are released by activated macrophages during
      lipopolysaccharide-induced septic shock or acetaminophen-induced liver injury. We
      show that extracellular NMI and IFP35 activate macrophages to release
      proinflammatory cytokines by activating nuclear factor-kappaB through the Toll
      like receptor 4 pathway. In addition, the serum levels of NMI are increased in
      patients who succumbed to severe inflammation. NMI deficiency reduces
      inflammatory responses and mortality in mouse models of sepsis and liver injury.
      We therefore propose that extracellular NMI and IFP35 exacerbate inflammation as
      DAMPs, making them potential therapeutic targets for clinical intervention.Damage
      associated molecular patterns (DAMP) are important mediators of innate immunity.
      Here the authors show that N-myc and STAT interactor (NMI) and interferon-induced
      protein 35 (IFP35) act as DAMPs to promote inflammation by activating macrophages
      via the Toll-like receptor 4 and NF-kappaB pathways.

PMID- 29038468
TI  - Barocaloric effect on graphene.
AB  - We describe how mechanical strain is able to control the flow of heat on a
      graphene sheet, since this material can either absorb or expel heat from/to a
      thermal reservoir, depending on the strain energy. In a similar fashion as the
      magneto- and electro-caloric effects, the present case considers the fact that a
      mechanical strain produces a pseudo-magnetic field that, on its turn, is
      responsible for the barocaloric effect. This result pushes graphene to the list
      of multicaloric materials.

PMID- 29038467
TI  - Self-sensing in Bacillus subtilis quorum-sensing systems.
AB  - Bacterial cell-cell signalling, or quorum sensing, is characterized by the
      secretion and groupwide detection of small diffusible signal molecules called
      autoinducers. This mechanism allows cells to coordinate their behaviour in a
      density-dependent manner. A quorum-sensing cell may directly respond to the
      autoinducers it produces in a cell-autonomous and quorum-independent manner, but
      the strength of this self-sensing effect and its impact on bacterial physiology
      are unclear. Here, we explore the existence and impact of self-sensing in the
      Bacillus subtilis ComQXP and Rap-Phr quorum-sensing systems. By comparing the
      quorum-sensing response of autoinducer-secreting and non-secreting cells in co
      culture, we find that secreting cells consistently show a stronger response than
      non-secreting cells. Combining genetic and quantitative analyses, we demonstrate
      this effect to be a direct result of self-sensing and rule out an indirect
      regulatory effect of the autoinducer production genes on response sensitivity. In
      addition, self-sensing in the ComQXP system affects persistence to antibiotic
      treatment. Together, these findings indicate the existence of self-sensing in the
      two most common designs of quorum-sensing systems of Gram-positive bacteria.

PMID- 29038466
TI  - Replication fork reversal triggers fork degradation in BRCA2-defective cells.
AB  - Besides its role in homologous recombination, the tumor suppressor BRCA2 protects
      stalled replication forks from nucleolytic degradation. Defective fork stability
      contributes to chemotherapeutic sensitivity of BRCA2-defective tumors by yet
      elusive mechanisms. Using DNA fiber spreading and direct visualization of
      replication intermediates, we report that reversed replication forks are entry
      points for fork degradation in BRCA2-defective cells. Besides MRE11 and PTIP, we
      show that RAD52 promotes stalled fork degradation and chromosomal breakage in
      BRCA2-defective cells. Inactivation of these factors restores reversed fork
      frequency and chromosome integrity in BRCA2-defective cells. Conversely,
      impairing fork reversal prevents fork degradation, but increases chromosomal
      breakage, uncoupling fork protection, and chromosome stability. We propose that
      BRCA2 is dispensable for RAD51-mediated fork reversal, but assembles stable RAD51
      nucleofilaments on regressed arms, to protect them from degradation. Our data
      uncover the physiopathological relevance of fork reversal and illuminate a
      complex interplay of homologous recombination factors in fork remodeling and
      stability.BRCA2 is involved in both homologous recombination (HR) and the
      protection of stalled replication forks from degradation. Here the authors reveal
      how HR factors cooperate in fork remodeling, showing that BRCA2 supports RAD51
      loading on the regressed arms of reversed replication forks to protect them from
      degradation.

PMID- 29038469
TI  - Spatial distribution of citizen science casuistic observations for different
      taxonomic groups.
AB  - Opportunistic citizen science databases are becoming an important way of
      gathering information on species distributions. These data are temporally and
      spatially dispersed and could have limitations regarding biases in the
      distribution of the observations in space and/or time. In this work, we test the
      influence of landscape variables in the distribution of citizen science
      observations for eight taxonomic groups. We use data collected through a
      Portuguese citizen science database (biodiversity4all.org). We use a zero
      inflated negative binomial regression to model the distribution of observations
      as a function of a set of variables representing the landscape features plausibly
      influencing the spatial distribution of the records. Results suggest that the
      density of paths is the most important variable, having a statistically
      significant positive relationship with number of observations for seven of the
      eight taxa considered. Wetland coverage was also identified as having a
      significant, positive relationship, for birds, amphibians and reptiles, and
      mammals. Our results highlight that the distribution of species observations, in
      citizen science projects, is spatially biased. Higher frequency of observations
      is driven largely by accessibility and by the presence of water bodies. We
      conclude that efforts are required to increase the spatial evenness of sampling
      effort from volunteers.

PMID- 29038470
TI  - Trios-promising in silico biomarkers for differentiating the effect of disease on
      the human microbiome network.
AB  - Recent advances in the HMP (human microbiome project) research have revealed
      profound implications of the human microbiome to our health and diseases. We
      postulated that there should be distinctive features associated with healthy
      and/or diseased microbiome networks. Following Occam's razor principle, we
      further hypothesized that triangle motifs or trios, arguably the simplest motif
      in a complex network of the human microbiome, should be sufficient to detect
      changes that occurred in the diseased microbiome. Here we test our hypothesis
      with six HMP datasets that cover five major human microbiome sites (gut, lung,
      oral, skin, and vaginal). The tests confirm our hypothesis and demonstrate that
      the trios involving the special nodes (e.g., most abundant OTU or MAO, and most
      dominant OTU or MDO, etc.) and interactions types (positive vs. negative) can be
      a powerful tool to differentiate between healthy and diseased microbiome samples.
      Our findings suggest that 12 kinds of trios (especially, dominantly inhibitive
      trio with mixed strategy, dominantly inhibitive trio with pure strategy, and
      fully facilitative strategy) may be utilized as in silico biomarkers for
      detecting disease-associated changes in the human microbiome, and may play an
      important role in personalized precision diagnosis of the human microbiome
      associated diseases.

PMID- 29038471
TI  - Myoblasts and macrophages are required for therapeutic morpholino antisense
      oligonucleotide delivery to dystrophic muscle.
AB  - Exon skipping is a promising therapeutic strategy for Duchenne muscular dystrophy
      (DMD), employing morpholino antisense oligonucleotides (PMO-AO) to exclude
      disruptive exons from the mutant DMD transcript and elicit production of
      truncated dystrophin protein. Clinical trials for PMO show variable and sporadic
      dystrophin rescue. Here, we show that robust PMO uptake and efficient production
      of dystrophin following PMO administration coincide with areas of myofiber
      regeneration and inflammation. PMO localization is sustained in inflammatory foci
      where it enters macrophages, actively differentiating myoblasts and newly forming
      myotubes. We conclude that efficient PMO delivery into muscle requires two
      concomitant events: first, accumulation and retention of PMO within inflammatory
      foci associated with dystrophic lesions, and second, fusion of PMO-loaded
      myoblasts into repairing myofibers. Identification of these factors accounts for
      the variability in clinical trials and suggests strategies to improve this
      therapeutic approach to DMD.Exon skipping is a strategy for the treatment of
      Duchenne muscular dystrophy, but has variable efficacy. Here, the authors show
      that dystrophin restoration occurs preferentially in areas of myofiber
      regeneration, where antisense oligonucleotides are stored in macrophages and
      delivered to myoblasts and newly formed myotubes.

PMID- 29038473
TI  - Soil biota contributions to soil aggregation.
AB  - Humankind depends on the sustainability of soils for its survival and well-being.
      Threatened by a rapidly changing world, our soils suffer from degradation and
      biodiversity loss, making it increasingly important to understand the role of
      soil biodiversity in soil aggregation-a key parameter for soil sustainability.
      Here, we provide evidence of the contribution of soil biota to soil aggregation
      on macro- and microaggregate scales, and evaluate how specific traits, soil biota
      groups and species interactions contribute to this. We conducted a global meta
      analysis comprising 279 soil biota species. Our study shows a clear positive
      effect of soil biota on soil aggregation, with bacteria and fungi generally
      appearing to be more important for soil aggregation than soil animals. Bacteria
      contribute strongly to both macro- and microaggregates while fungi strongly
      affect macroaggregation. Motility, body size and population density were
      important traits modulating effect sizes. Investigating species interactions
      across major taxonomic groups revealed their beneficial impact on soil
      aggregation. At the broadest level, our results highlight the need to consider
      biodiversity as a causal factor in soil aggregation. This will require a shift
      from the current management and physicochemical perspective to an approach that
      fully embraces the significance of soil organisms, their diversity and
      interactions.

PMID- 29038472
TI  - Phage-assisted continuous evolution of proteases with altered substrate
      specificity.
AB  - Here we perform phage-assisted continuous evolution (PACE) of TEV protease, which
      canonically cleaves ENLYFQS, to cleave a very different target sequence, HPLVGHM,
      that is present in human IL-23. A protease emerging from ~2500 generations of
      PACE contains 20 non-silent mutations, cleaves human IL-23 at the target peptide
      bond, and when pre-mixed with IL-23 in primary cultures of murine splenocytes
      inhibits IL-23-mediated immune signaling. We characterize the substrate
      specificity of this evolved enzyme, revealing shifted and broadened specificity
      changes at the six positions in which the target amino acid sequence differed.
      Mutational dissection and additional protease specificity profiling reveal the
      molecular basis of some of these changes. This work establishes the capability of
      changing the substrate specificity of a protease at many positions in a practical
      time scale and provides a foundation for the development of custom proteases that
      catalytically alter or destroy target proteins for biotechnological and
      therapeutic applications.Proteases are promising therapeutics to treat diseases
      such as hemophilia which are due to endogenous protease deficiency. Here the
      authors use phage-assisted continuous evolution to evolve a variant TEV protease
      with altered target peptide sequence specificities.

PMID- 29038474
TI  - A shared Runx1-bound Zbtb16 enhancer directs innate and innate-like lymphoid
      lineage development.
AB  - Zbtb16-encoded PLZF is a signature transcription factor (TF) that directs the
      acquisition of T-helper effector programs during the development of multiple
      innate lymphocyte lineages, including natural killer T cell, innate lymphoid
      cell, mucosal-associated invariant T cell and gammadelta lineages. PLZF is also
      essential in osteoblast and spermatogonial development. How Zbtb16 itself is
      regulated in different lineages is incompletely understood. Here, by systematic
      CRISPR/Cas9-assisted deletions of chromatin accessible regions within the Zbtb16
      locus in mouse, we identify a critical enhancer controlling PLZF expression
      exclusively in innate lymphoid lineages. Multiple sites within this enhancer
      express canonical motifs for the TF Runx1, which is essential for the development
      of these lineages. Notably, some regulatory sites control the kinetic rather than
      the overall level of PLZF expression. Thus, our comprehensive, unbiased analysis
      of regulatory elements in vivo reveals critical mechanisms of Zbtb16 regulation
      shared between innate and innate-like lymphoid lineages. Zbtb16-encoded
      transcription factor PLZF directs the differentiation of multiple innate and
      innate-like cell lineages, but how Zbtb16 itself is regulated remains unclear.
      Here the authors show, using CRISPR gene editing, ATAC-seq and ChIP-seq, that
      specific Runx1-bound enhancer elements critically modulate lineage-dependent
      expressions of PLZF.

PMID- 29038475
TI  - Climate and permafrost effects on the chemistry and ecosystems of High Arctic
      Lakes.
AB  - Permafrost exerts an important control over hydrological processes in Arctic
      landscapes and lakes. Recent warming and summer precipitation has the potential
      to alter water availability and quality in this environment through thermal
      perturbation of near surface permafrost and increased mobility of previously
      frozen solutes to Arctic freshwaters. We present a unique thirteen-year record
      (2003-16) of the physiochemical properties of two High Arctic lakes and show that
      the concentration of major ions, especially SO42-, has rapidly increased up to
      500% since 2008. This hydrochemical change has occurred synchronously in both
      lakes and ionic ratio changes in the lakes indicate that the source for the SO42-
      is compositionally similar to terrestrial sources arising from permafrost thaw.
      Record summer temperatures during this period (2003-16) following over 100 years
      of warming and summer precipitation in this polar desert environment provide
      likely mechanisms for this rapid chemical change. An abrupt limnological change
      is also reflected in the otolith chemistry and improved relative condition of
      resident Arctic char (Salvelinus alpinus) and increased diatom diversity point to
      a positive ecosystem response during the same period.

PMID- 29038476
TI  - Pro-angiogenic effect of RANTES-loaded polysaccharide-based microparticles for a
      mouse ischemia therapy.
AB  - Peripheral arterial disease results from the chronic obstruction of arteries
      leading to critical hindlimb ischemia. The aim was to develop a new therapeutic
      strategy of revascularization by using biodegradable and biocompatible
      polysaccharides-based microparticles (MP) to treat the mouse hindlimb ischemia.
      For this purpose, we deliver the pro-angiogenic chemokine Regulated upon
      Activation, Normal T-cell Expressed and Secreted (RANTES)/CCL5 in the mouse
      ischemic hindlimb, in solution or incorporated into polysaccharide-based
      microparticles. We demonstrate that RANTES-loaded microparticles improve the
      clinical score, induce the revascularization and the muscle regeneration in
      injured mice limb. To decipher the mechanisms underlying RANTES effects in vivo,
      we demonstrate that RANTES increases the spreading, the migration of human
      endothelial progenitor cells (EPC) and the formation of vascular network. The
      main receptors of RANTES i.e. CCR5, syndecan-4 and CD44 expressed at endothelial
      progenitor cell surface are involved in RANTES-induced in vitro biological
      effects on EPC. By using two RANTES mutants, [E66A]-RANTES with impaired ability
      to oligomerize, and [44AANA47]-RANTES mutated in the main RANTES
      glycosaminoglycan binding site, we demonstrate that both chemokine
      oligomerization and binding site to glycosaminoglycans are essential for RANTES
      induced angiogenesis in vitro. Herein we improved the muscle regeneration and
      revascularization after RANTES-loaded MP local injection in mice hindlimb
      ischemia.

PMID- 29038478
TI  - Herbivores increase the global availability of nutrients over millions of years.
AB  - Can the presence of herbivores increase global nutrient availability? Animals
      disperse vital nutrients through ecosystems, increasing the spatial availability
      of these nutrients. Large herbivores are especially important for the dispersal
      of vital nutrients due to their long food passage times and day ranges, and large
      herbivores from past periods (the Pleistocene) may have increased nutrient
      concentrations on the continental scale. However, such results have been
      demonstrated theoretically but not yet empirically. Models suggest that the
      Pennsylvanian subperiod (323-299 million years ago), with no tetrapod terrestrial
      herbivores, would have had fewer, less-well-distributed nutrients than the
      Cretaceous period (145-66 million years ago), with the largest terrestrial
      herbivores ever-the sauropods. Here, I show that these models are supported
      empirically by remnant plant material (coal deposits) from the Cretaceous (N =
      680), which had significantly (P < 0.00001) increased concentrations (136%) and
      decreased spatial heterogeneity (22%) of plant-important rock-derived nutrients
      compared with the Pennsylvanian subperiod (N = 4,996). Non-biotic physical
      processes, such as weathering rates, cannot account for such differences, because
      aluminium-a nutrient not important for plants and animals, but weathered in a
      similar manner to the above elements-showed no significant difference between the
      two periods, suggesting that these large changes were driven by plant-herbivore
      interactions. Populations of large wild herbivores are currently at historical
      lows; therefore, we are potentially losing a key ecosystem service.

PMID- 29038477
TI  - Long non-coding HCG18 promotes intervertebral disc degeneration by sponging miR
      146a-5p and regulating TRAF6 expression.
AB  - Intervertebral disc degeneration (IDD) is associated with the deterioration of
      nucleus pulposus (NP) cells due to hypertrophic differentiation and
      calcification. Emerging studies have shown that long noncoding RNAs (lncRNAs)
      play critical roles in the development of IDD. Using bioinformatics prediction,
      we hereby sought to identify the lncRNAs that regulate the expression of microRNA
      146a-5p (miR-146a-5p), an IDD-related inflammatory factor. Our study demonstrated
      that lncRNA HCG18 acted as an endogenous sponge to down-regulate miR-146a-5p
      expression in the NP cells by directly binding to miR-146a-5p. In addition, HCG18
      expression was up-regulated in the patients with IDD, bulging or herniated discs,
      and its level was positively correlated with the disc degeneration grade. In
      vitro, miR-146a-5p up-regulation HCG18 retarded the growth of NP cells by
      decreasing S phase of cell cycle, inducing cell apoptosis, recruitment of
      macrophages and hypercalcification. Conversely, down-regulation of miR-146a-5p
      exerted opposite effects. Furthermore, we elucidated that TRAF6, a target gene by
      miR-146a-5p, was modulated by HCG18 expression. Restore of TRAF6 expression by
      virus infection reserved the effect of HCG18 on the NP cells. Altogether, our
      data indicated that HCG18 suppressed the growth of NP cells and promoted the IDD
      development via the miR-146a-5p/TRAF6/NFkappaB axis.

PMID- 29038479
TI  - Probing ligand recognition of the opioid pan antagonist AT-076 at nociceptin,
      kappa, mu, and delta opioid receptors through structure-activity relationships.
AB  - Few opioid ligands binding to the three classic opioid receptor subtypes, mu,
      kappa and delta, have high affinity at the fourth opioid receptor, the
      nociceptin/orphanin FQ receptor (NOP). We recently reported the discovery of AT
      076 (1), (R)-7-hydroxy-N-((S)-1-(4-(3-hydroxyphenyl)piperidin-1-yl)-3-methylbutan
      2-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, a pan antagonist with
      nanomolar affinity for all four subtypes. Since AT-076 binds with high affinity
      at all four subtypes, we conducted a structure-activity relationship (SAR) study
      to probe ligand recognition features important for pan opioid receptor activity,
      using chemical modifications of key pharmacophoric groups. SAR analysis of the
      resulting analogs suggests that for the NOP receptor, the entire AT-076 scaffold
      is crucial for high binding affinity, but the binding mode is likely different
      from that of NOP antagonists C-24 and SB-612111 bound in the NOP crystal
      structure. On the other hand, modifications of the 3-hydroxyphenyl pharmacophore,
      but not the 7-hydroxy Tic pharmacophore, are better tolerated at kappa and mu
      receptors and yield very high affinity multifunctional (e.g. 12) or highly
      selective (e.g. 16) kappa ligands. With the availability of the opioid receptor
      crystal structures, our SAR analysis of the common chemotype of AT-076 suggests
      rational approaches to modulate binding selectivity, enabling the design of
      multifunctional or selective opioid ligands from such scaffolds.

PMID- 29038480
TI  - Parallels between DNA and collagen - comparing elastic models of the double and
      triple helix.
AB  - Multi-stranded helices are widespread in nature. The interplay of polymeric
      properties with biological function is seldom discussed. This study probes
      analogies between structural and mechanical properties of collagen and DNA. We
      modeled collagen with Eulerian rotational and translational parameters of
      adjacent rungs in the triple-helix ladder and developed statistical potentials by
      extracting the dispersion of the parameters from a database of atomic-resolution
      structures. The resulting elastic model provides a common quantitative way to
      describe collagen deformations upon interacting with integrins or matrix
      metalloproteinase and DNA deformations upon protein binding. On a larger scale,
      deformations in Type I collagen vary with a periodicity consistent with the D
      periodic banding of higher-order fibers assemblies. This indicates that
      morphologies of natural higher-order collagen packing might be rooted in the
      characteristic deformation patterns.

PMID- 29038481
TI  - The social and cultural roots of whale and dolphin brains.
AB  - Encephalization, or brain expansion, underpins humans' sophisticated social
      cognition, including language, joint attention, shared goals, teaching, consensus
      decision-making and empathy. These abilities promote and stabilize cooperative
      social interactions, and have allowed us to create a 'cognitive' or 'cultural'
      niche and colonize almost every terrestrial ecosystem. Cetaceans (whales and
      dolphins) also have exceptionally large and anatomically sophisticated brains.
      Here, by evaluating a comprehensive database of brain size, social structures and
      cultural behaviours across cetacean species, we ask whether cetacean brains are
      similarly associated with a marine cultural niche. We show that cetacean
      encephalization is predicted by both social structure and by a quadratic
      relationship with group size. Moreover, brain size predicts the breadth of social
      and cultural behaviours, as well as ecological factors (diversity of prey types
      and to a lesser extent latitudinal range). The apparent coevolution of brains,
      social structure and behavioural richness of marine mammals provides a unique and
      striking parallel to the large brains and hyper-sociality of humans and other
      primates. Our results suggest that cetacean social cognition might similarly have
      arisen to provide the capacity to learn and use a diverse set of behavioural
      strategies in response to the challenges of social living.

PMID- 29038482
TI  - Selective binding of choline by a phosphate-coordination-based triple helicate
      featuring an aromatic box.
AB  - In nature, proteins have evolved sophisticated cavities tailored for capturing
      target guests selectively among competitors of similar size, shape, and charge.
      The fundamental principles guiding the molecular recognition, such as self
      assembly and complementarity, have inspired the development of biomimetic
      receptors. In the current work, we report a self-assembled triple anion helicate
      (host 2) featuring a cavity resembling that of the choline-binding protein ChoX,
      as revealed by crystal and density functional theory (DFT)-optimized structures,
      which binds choline in a unique dual-site-binding mode. This similarity in
      structure leads to a similarly high selectivity of host 2 for choline over its
      derivatives, as demonstrated by the NMR and fluorescence competition experiments.
      Furthermore, host 2 is able to act as a fluorescence displacement sensor for
      discriminating choline, acetylcholine, L-carnitine, and glycine betaine
      effectively.The choline-binding protein ChoX exhibits a synergistic dual-site
      binding mode that allows it to discriminate choline over structural analogues.
      Here, the authors design a biomimetic triple anion helicate receptor whose
      selectivity for choline arises from a similar binding mechanism.

PMID- 29038483
TI  - Quantitative microglia analyses reveal diverse morphologic responses in the rat
      cortex after diffuse brain injury.
AB  - Determining regions of altered brain physiology after diffuse brain injury is
      challenging. Microglia, brain immune cells with ramified and dynamically moving
      processes, constantly surveil the parenchyma for dysfunction which, when present,
      results in a changed morphology. Our purpose was to define the spatiotemporal
      changes in microglia morphology over 28 days following rat midline fluid
      percussion injury (mFPI) as a first step in exploiting microglia morphology to
      reflect altered brain physiology. Microglia morphology was quantified from
      histological sections using Image J skeleton and fractal analysis procedures at
      three time points and in three regions post-mFPI: impact site, primary
      somatosensory cortex barrel field (S1BF), and a remote region. Microglia
      ramification (process length/cell and endpoints/cell) decreased in the impact and
      S1BF but not the remote region (p < 0.05). Microglia complexity was decreased in
      the S1BF (p = 0.003) and increased in the remote region (p < 0.02). Rod-shaped
      microglia were present in the S1BF and had a 1.8:1.0 length:width ratio. An in
      depth quantitative morphologic analysis revealed diverse and widespread changes
      to microglia morphology in the cortex post-mFPI. Due to their close link to
      neuronal function, changes in microglia morphology, summarized in this study,
      likely reflect altered physiology with diverse and widespread impact on neuronal
      and circuit function.

PMID- 29038484
TI  - Mechanical on-chip microwave circulator.
AB  - Nonreciprocal circuit elements form an integral part of modern measurement and
      communication systems. Mathematically they require breaking of time-reversal
      symmetry, typically achieved using magnetic materials and more recently using the
      quantum Hall effect, parametric permittivity modulation or Josephson
      nonlinearities. Here we demonstrate an on-chip magnetic-free circulator based on
      reservoir-engineered electromechanic interactions. Directional circulation is
      achieved with controlled phase-sensitive interference of six distinct electro
      mechanical signal conversion paths. The presented circulator is compact, its
      silicon-on-insulator platform is compatible with both superconducting qubits and
      silicon photonics, and its noise performance is close to the quantum limit. With
      a high dynamic range, a tunable bandwidth of up to 30 MHz and an in situ
      reconfigurability as beam splitter or wavelength converter, it could pave the way
      for superconducting qubit processors with multiplexed on-chip signal processing
      and readout.Nonreciprocal optical elements often require magnetic materials in
      order to break time-reversal symmetry. Here, Barzanjeh et al. demonstrate a
      magnetic-free on-chip microwave circulator that utilizes the interference from
      six electro-mechanical signal paths.

PMID- 29038485
TI  - A versatile pretargeting approach for tumour-selective delivery and activation of
      TNF superfamily members.
AB  - TNFR superfamily (TNFRSF) members have important immunoregulatory functions and
      are of clear interest for cancer immunotherapy. Various TNFRSF agonists have been
      clinically evaluated, but have met with limited efficacy and/or toxicity. Recent
      insights indicate that 'first-generation' TNFRSF agonists lack efficacy as they
      do not effectively cross-link their corresponding receptor. Reversely, ubiquitous
      TNFRSF receptor(s) cross-linking by CD40 and Fas agonistic antibodies resulted in
      dose-limiting liver toxicity. To overcome these issues, we developed a novel
      pretargeting strategy exploiting recombinant fusion proteins in which a soluble
      form of TRAIL, FasL or CD40L is genetically fused to a high-affinity anti
      fluorescein scFv antibody fragment (scFvFITC). Fusion proteins scFvFITC:sTRAIL
      and scFvFITC:sFasL induced potent target antigen-restricted apoptosis in a panel
      of cancer lines and in primary patient-derived cancer cells, but only when
      pretargeted with a relevant FITC-labelled antitumour antibody. In a similar
      pretargeting setting, fusion protein scFvFITC:sCD40L promoted tumour-directed
      maturation of immature monocyte-derived dendritic cells (iDCs). This novel tumour
      selective pretargeting approach may be used to improve efficacy and/or reduce
      possible off-target toxicity of TNFSF ligands for cancer immunotherapy.

PMID- 29038486
TI  - Experimental investigation on the geometry of GHZ states.
AB  - Greenberger-Horne-Zeilinger (GHZ) states and their mixtures exhibit fascinating
      properties. A complete basis of GHZ states can be constructed by properly
      choosing local basis rotations. We demonstrate this experimentally for the
      Hilbert space [Formula: see text] by entangling two photons in polarization and
      orbital angular momentum. Mixing GHZ states unmasks different entanglement
      features based on their particular local geometrical connectedness. In
      particular, a specific GHZ state in a complete orthonormal basis has a "twin" GHZ
      state for which equally mixing leads to full separability in opposition to any
      other basis-state. Exploiting these local geometrical relations provides a
      toolbox for generating specific types of multipartite entanglement, each
      providing different benefits in outperforming classical devices. Our experiment
      investigates these GHZ's properties exploiting the HMGH framework which allows us
      to study the geometry for the different depths of entanglement in our system and
      showing a good stability and fidelity thus admitting a scaling in degrees of
      freedom and advanced operational manipulations.

PMID- 29038487
TI  - The microbiome beyond the horizon of ecological and evolutionary theory.
AB  - The ecological and evolutionary study of community formation, diversity, and
      stability is rooted in general theory and reinforced by decades of system
      specific empirical work. Deploying these ideas to study the assembly, complexity,
      and dynamics of microbial communities living in and on eukaryotes has proved
      seductive, but challenging. The success of this research endeavour depends on our
      capacity to observe and characterize the distributions, abundances, and
      functional traits of microbiota, representing an array of technical and
      analytical challenges. Furthermore, a number of unique characteristics of
      microbial species, such as horizontal gene transfer, the production of public
      goods, toxin and antibiotic production, rapid evolution, and feedbacks between
      the microbiome and its host, are not easily accommodated by current ecological
      and evolutionary theory. Here we highlight potential pitfalls in the application
      of existing theoretical tools without careful consideration of the unique
      complexities of the microbiome, focusing particularly on the issue of human
      health, and anchoring our discussion in existing empirical evidence.

PMID- 29038489
TI  - Controlling the Quantum State with a time varying potential.
AB  - The problem of controlling the quantum state of a system is investigated using a
      time varying potential. As a concrete example we study the problem of a particle
      in a box with a periodically oscillating infinite square-well potential, from
      which we obtain results that can be applied to systems with periodically
      oscillating boundary conditions. We derive an analytic expression for the
      frequencies of resonance between states, and against standard intuition, we show
      how to use this behavior to control the quantum state of the system at will. In
      particular, we offer as an example the transition from the ground state to the
      first excited state of the square well potential. At first sight, it may be
      counter intuitive that we can control the state of such a quantum Hamiltonian, as
      the Schrodinger equation conserves the norm of the wave function. In this
      manuscript, we show how that can be achieved.

PMID- 29038490
TI  - A doping-less junction-formation mechanism between n-silicon and an atomically
      thin boron layer.
AB  - The interest in nanostructures of silicon and its dopants has significantly
      increased. We report the creation of an ultimately-shallow junction at the
      surface of n-type silicon with excellent electrical and optical characteristics
      made by depositing an atomically thin boron layer at a relatively low temperature
      where no doping of silicon is expected. The presented experimental results and
      simulations of the ab initio quantum mechanics molecular dynamics prove that the
      structure of this new type of junction differs from all other known rectifying
      junctions at this time. An analysis of the junction formation has led to the
      conclusion that the chemical interaction between the surface atoms of crystalline
      silicon and the first atomic layer of the as-deposited amorphous boron is the
      dominant factor leading to the formation of a depletion zone in the crystalline
      silicon which originates from the surface. The simulation results show a very
      strong electric field across the c-Si/a-B interface systems where the charge
      transfer occurs mainly from the interface Si atoms to the neighboring B atoms.
      This electric field appears to be responsible for the creation of a depletion
      zone in the n-silicon resulting in a rectifying junction-formation between the n
      silicon and the atomically thin boron layer.

PMID- 29038488
TI  - MCM2-regulated functional networks in lung cancer by multi-dimensional proteomic
      approach.
AB  - DNA replication control is vital for maintaining genome stability and the cell
      cycle, perhaps most notably during cell division. Malignancies often exhibit
      defective minichromosome maintenance protein 2 (MCM2), a cancer proliferation
      biomarker that serves as a licensing factor in the initiation of DNA replication.
      MCM2 is also known to be one of the ATPase active sites that facilitates
      conformational changes and drives DNA unwinding at the origin of DNA replication.
      However, the biological networks of MCM2 in lung cancer cells via protein
      phosphorylation remain unmapped. The RNA-seq datasets from The Cancer Genome
      Atlas (TCGA) revealed that MCM2 overexpression is correlated with poor survival
      rate in lung cancer patients. To uncover MCM2-regulated functional networks in
      lung cancer, we performed multi-dimensional proteomic approach by integrating
      analysis of the phosphoproteome and proteome, and identified a total of 2361
      phosphorylation sites on 753 phosphoproteins, and 4672 proteins. We found that
      the deregulation of MCM2 is involved in lung cancer cell proliferation, the cell
      cycle, and migration. Furthermore, HMGA1S99 phosphorylation was found to be
      differentially expressed under MCM2 perturbation in opposite directions, and
      plays an important role in regulating lung cancer cell proliferation. This study
      therefore enhances our capacity to therapeutically target cancer-specific
      phosphoproteins.

PMID- 29038491
TI  - Understanding activity and selectivity of metal-nitrogen-doped carbon catalysts
      for electrochemical reduction of CO2.
AB  - Direct electrochemical reduction of CO2 to fuels and chemicals using renewable
      electricity has attracted significant attention partly due to the fundamental
      challenges related to reactivity and selectivity, and partly due to its
      importance for industrial CO2-consuming gas diffusion cathodes. Here, we present
      advances in the understanding of trends in the CO2 to CO electrocatalysis of
      metal- and nitrogen-doped porous carbons containing catalytically active M-N x
      moieties (M = Mn, Fe, Co, Ni, Cu). We investigate their intrinsic catalytic
      reactivity, CO turnover frequencies, CO faradaic efficiencies and demonstrate
      that Fe-N-C and especially Ni-N-C catalysts rival Au- and Ag-based catalysts. We
      model the catalytically active M-N x moieties using density functional theory and
      correlate the theoretical binding energies with the experiments to give
      reactivity-selectivity descriptors. This gives an atomic-scale mechanistic
      understanding of potential-dependent CO and hydrocarbon selectivity from the M-N
      x moieties and it provides predictive guidelines for the rational design of
      selective carbon-based CO2 reduction catalysts.Inexpensive and selective
      electrocatalysts for CO2 reduction hold promise for sustainable fuel production.
      Here, the authors report N-coordinated, non-noble metal-doped porous carbons as
      efficient and selective electrocatalysts for CO2 to CO conversion.

PMID- 29038492
TI  - Correlation of Plasma EGF with Striatal Dopamine Transporter Availability in
      Healthy Subjects.
AB  - We aimed to evaluate the association between plasma epidermal growth factor (EGF)
      and the availability of dopamine transporter (DAT) measured from 123I-FP-CIT
      single-photon emission computed tomography in healthy controls in this study.
      Volume of interest template was applied to measure specific binding ratios (SBRs)
      of caudate nucleus, putamen, and striatum representing DAT availability as
      follows; SBR = (target- cerebellum)/cerebellum. Plasma EGF was negatively
      correlated with the availabilities of both caudate nucleus (r = -0.261, p =
      0.019), and putamen (r = -0.341, p = 0.002). After dividing subjects according to
      Apo E genotyping, DAT availability of caudate nucleus of Apo e4 non-carriers (n =
      60) showed the positive correlation with cerebrospinal fluid (CSF) alpha
      synuclein (r = 0.264, p = 0.042). Plasma EGF was negatively correlated with DAT
      availabilities of Apo e4 non-carriers. Further studies are needed to clarify
      underlying mechanisms of this phenomenon.

PMID- 29038493
TI  - Flexible parental care: Uniparental incubation in biparentally incubating
      shorebirds.
AB  - The relative investment of females and males into parental care might depend on
      the population's adult sex-ratio. For example, all else being equal, males should
      be the more caring sex if the sex-ratio is male biased. Whether such outcomes are
      evolutionary fixed (i.e. related to the species' typical sex-ratio) or whether
      they arise through flexible responses of individuals to the current population
      sex-ratio remains unclear. Nevertheless, a flexible response might be limited by
      the evolutionary history of the species, because one sex may have lost the
      ability to care or because a single parent cannot successfully raise the brood.
      Here, we demonstrate that after the disappearance of one parent, individuals from
      8 out of 15 biparentally incubating shorebird species were able to incubate
      uniparentally for 1-19 days (median = 3, N = 69). Moreover, their daily
      incubation rhythm often resembled that of obligatory uniparental shorebird
      species. Although it has been suggested that in some biparental shorebirds
      females desert their brood after hatching, we found both sexes incubating
      uniparentally. Strikingly, in 27% of uniparentally incubated clutches - from 5
      species - we documented successful hatching. Our data thus reveal the potential
      for a flexible switch from biparental to uniparental care.

PMID- 29038494
TI  - A Study of the Brain Abnormalities of Post-Stroke Depression in Frontal Lobe
      Lesion.
AB  - Post stroke depression (PSD) is a serious complication of stroke. Brain imaging
      is an important method of studying the mechanism of PSD. However, few studies
      have focused on the single lesion location. The aim of this study was to
      investigate the brain mechanism of frontal lobe PSD using combined voxel-based
      morphometry (VBM) and functional magnetic resonance imaging (fMRI). In total, 30
      first-time ischemic frontal lobe stroke patients underwent T1 weighted MRI and
      resting-state fMRI scans. Clinical assessments included the 24-item Hamilton
      Rating Scale for Depression, the National Institutes of Health Stroke Scale, and
      the Mini-Mental State Examination. In our result, decreased gray matter (GM)
      volume in patients was observed in the prefrontal cortex, limbic system and motor
      cortex. The anterior cingulate cortex, selected as a seed to perform connectivity
      analyses, showed a greatly decreased functional connectivity with the prefrontal
      cortex, cingulate cortex, and motor cortex, but had an increased functional
      connectivity with the hippocampus gyrus, parahippocampa gyrus, insular, and
      amygdala. Stroke lesion location reduces excitability of brain areas in the
      ipsilateral brain. PSD affects mood through the brain network of the prefrontal
      limbic circuit. Some brain networks, including motor cortex and the default mode
      network, show other characteristics of PSD brain network.

PMID- 29038495
TI  - A method to determine pharmacokinetic parameters based on andante constant-rate
      intravenous infusion.
AB  - On account of the disturbance from the distribution phase, the concentration-time
      curve of drugs cannot fully reflect the characteristics of elimination, and thus,
      it is difficult for present methods to obtain ideal pharmacokinetic parameters.
      This paper presents a method to determine pharmacokinetic parameters based on an
      andante constant-rate intravenous infusion. A mathematical model of the constant
      rate intravenous infusion combined with the elimination of first-order kinetics
      was established. During infusion, the accumulation tendency of drugs was deduced
      as [Formula: see text] using the principle of calculus. Then, the method to
      determine the pharmacokinetic parameters was summed up. After collecting the
      blood drug concentration (C t ) -time (t) data from a constant-rate (v) infusion
      period, an exponential regression analysis was conducted to obtain the
      elimination rate constant (K) and plateau concentration (C ss ). Then, the half
      life (t 1/2 ), apparent volume of distribution (V d ) and clearance rate (CL)
      were calculated based on the equations, t 1/2  = 0.693/K, V d  = (v/K)/C ss and
      CL = v/C ss , respectively. In addition, an application example of cimetidine in
      a beagle dog was used to demonstrate the implementation process of the method.

PMID- 29038497
TI  - Non-steroidal anti-inflammatory drug delays corneal wound healing by reducing
      production of 12-hydroxyheptadecatrienoic acid, a ligand for leukotriene B4
      receptor 2.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to reduce
      inflammation by suppressing cyclooxygenases (COXs). NSAID eye drops are
      frequently prescribed after ocular surgery to reduce inflammation and pain, but
      this treatment has clinically significant side effects, including corneal ulcer
      and perforation. The molecular mechanisms underlying these side effects remain
      unknown. Recently, the COX product 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid
      (12-HHT) was identified as an endogenous ligand for leukotriene B4 receptor 2
      (BLT2), which is important in maintenance of epithelial homeostasis. We
      hypothesized that NSAID-dependent corneal damage is caused by reduced production
      of 12-HHT. Diclofenac eye drops decreased the abundance of downstream products of
      COX and delayed corneal wound healing in BALB/c mice. Expression of BLT2 was
      observed in murine ocular tissues including cornea, and in human corneal
      epithelial cell line and human primary corneal epithelial cells. In BLT2-knockout
      mice, corneal wound healing was delayed, but the diclofenac-dependent delay in
      corneal wound healing disappeared. 12-HHT accelerated wound closure both in BLT2
      transfected corneal cell line and human primary corneal epithelial cells. Thus,
      our results reveal that NSAIDs delay corneal wound healing by inhibiting 12-HHT
      production, and suggest that stimulation of the 12-HHT/BLT2 axis represents a
      novel therapeutic approach to corneal wound healing.

PMID- 29038496
TI  - The Hsp70 homolog Ssb affects ribosome biogenesis via the TORC1-Sch9 signaling
      pathway.
AB  - The Hsp70 Ssb serves a dual role in de novo protein folding and ribosome
      biogenesis; however, the mechanism by which Ssb affects ribosome production is
      unclear. Here we establish that Ssb is causally linked to the regulation of
      ribosome biogenesis via the TORC1-Sch9 signaling pathway. Ssb is bound to Sch9
      posttranslationally and required for the TORC1-dependent phosphorylation of Sch9
      at T737. Also, Sch9 lacking phosphorylation at T737 displays significantly
      reduced kinase activity with respect to targets involved in the regulation of
      ribosome biogenesis. The absence of either Ssb or Sch9 causes enhanced ribosome
      aggregation. Particularly with respect to proper assembly of the small ribosomal
      subunit, SSB and SCH9 display strong positive genetic interaction. In
      combination, the data indicate that Ssb promotes ribosome biogenesis not only via
      cotranslational protein folding, but also posttranslationally via interaction
      with natively folded Sch9, facilitating access of the upstream kinase TORC1 to
      Sch9-T737.The yeast Hsp70 homolog Ssb is a chaperone that binds translating
      ribosomes where it is thought to function primarily by promoting nascent peptide
      folding. Here the authors find that the ribosome biogenesis defect associated
      with the loss of Ssb is attributable to a specific disruption in TORC1 signaling
      rather than defects in ribosomal protein folding.

PMID- 29038498
TI  - Environmental and behavioral changes may influence the exposure of an Arctic apex
      predator to pathogens and contaminants.
AB  - Recent decline of sea ice habitat has coincided with increased use of land by
      polar bears (Ursus maritimus) from the southern Beaufort Sea (SB), which may
      alter the risks of exposure to pathogens and contaminants. We assayed blood
      samples from SB polar bears to assess prior exposure to the pathogens Brucella
      spp., Toxoplasma gondii, Coxiella burnetii, Francisella tularensis, and Neospora
      caninum, estimate concentrations of persistent organic pollutants (POPs), and
      evaluate risk factors associated with exposure to pathogens and POPs. We found
      that seroprevalence of Brucella spp. and T. gondii antibodies likely increased
      through time, and provide the first evidence of exposure of polar bears to C.
      burnetii, N. caninum, and F. tularensis. Additionally, the odds of exposure to T.
      gondii were greater for bears that used land than for bears that remained on the
      sea ice during summer and fall, while mean concentrations of the POP chlordane
      (SigmaCHL) were lower for land-based bears. Changes in polar bear behavior
      brought about by climate-induced modifications to the Arctic marine ecosystem may
      increase exposure risk to certain pathogens and alter contaminant exposure
      pathways.

PMID- 29038499
TI  - Replacing conventional decontamination of hatching eggs with a natural defense
      strategy based on antimicrobial, volatile pyrazines.
AB  - The treatment of hatching eggs relies on classic yet environmentally harmful
      decontamination methods such as formaldehyde fumigation. We evaluated bacteria
      derived volatiles as a replacement within a fundamentally novel approach based on
      volatile organic compounds (VOCs), which are naturally involved in microbial
      communication and antagonism due to their high antimicrobial efficiency. Pyrazine
      (5-isobutyl-2,3-dimethylpyrazine) was applied passively and actively in
      prototypes of a pre-industry-scale utilization. Altogether, pyrazine
      decontamination rates of up to 99.6% were observed, which is comparable to
      formaldehyde fumigation. While active evaporation was highly efficient in all
      experiments, passive treatment showed reducing effects in two of four tested
      groups only. These results were confirmed by visualization using LIVE/DEAD
      staining microscopy. The natural egg shell microbiome was characterized by an
      unexpected bacterial diversity of Pseudomonadales, Enterobacteriales,
      Sphingomonadales, Streptophyta, Burkholderiales, Actinomycetales,
      Xanthomonadales, Rhizobiales, Bacillales, Clostridiales, Lactobacillales, and
      Flavobacteriales members. Interestingly, we found that especially low pyrazine
      concentrations lead to a microbiome shift, which can be explained by varying
      antimicrobial effects on different microorganisms. Micrococcus spp., which are
      linked to embryonic death and reduced hatchability, was found to be highly
      sensitive to pyrazines. Taken together, pyrazine application was shown to be a
      promising, environmentally friendly alternative for fumigation treatments of
      hatchery eggs.

PMID- 29038500
TI  - Role of Mast Cells in clearance of Leishmania through extracellular trap
      formation.
AB  - Mast Cells (MCs) are one of the first immune cells encountered by invading
      pathogens. Their presence in large numbers in the superficial dermis, where
      Leishmania is encountered, suggests that they may play a critical role in immune
      responses to Leishmania. In this study the interactions of Leishmania donovani,
      the causative agent of visceral Leishmaniasis, and Leishmania tropica, the
      causative agent of cutaneous Leishmaniasis with MCs were studied. Co-culture of
      Leishmania with Peritoneal Mast Cells (PMCs) from BALB/c mice and Rat Basophilic
      Leukaemia (RBL-2H3) MCs led to significant killing of L. tropica and to a lesser
      extent of L. donovani. Also, while there was significant uptake of L. tropica by
      MCs, L. donovani was not phagocytosed. There was significant generation of
      Reactive Oxygen Species (ROS) by MCs on co-culture with these species of
      Leishmania which may contribute to their clearance. Interactions of MCs with
      Leishmania led to generation of MC extracellular traps comprising of DNA,
      histones and tryptase probably to ensnare these pathogens. These results clearly
      establish that MCs may contribute to host defences to Leishmania in a
      differential manner, by actively taking up these pathogens, and also by mounting
      effector responses for their clearance by extracellular means.

PMID- 29038501
TI  - Effects of charge-modifying mutations in histone H2A alpha3-domain on nucleosome
      stability assessed by single-pair FRET and MD simulations.
AB  - Nucleosomes are important for chromatin compaction and gene regulation; their
      integrity depends crucially on the structural properties of the histone tails.
      Recent all-atom molecular dynamics simulations revealed that removal of the N
      terminal tails of histone H3, known to destabilize nucleosomes, causes a
      rearrangement of two arginines of histone H2A, namely R81 and R88 by altering the
      electrostatic environment of the H2A alpha3 domain. Whether this rearrangement is
      the cause or the effect of decreased stability, is unclear. Here, we emulate the
      altered electrostatic environment that was found after H3 tail clipping through
      charge-modifying mutations to decouple its impact on intranucleosomal
      interactions from that of the histone tails. Forster resonance energy transfer
      experiments on recombinant nucleosomes and all-atom molecular dynamics
      simulations reveal a compensatory role of those amino acids in nucleosome
      stability. The simulations indicate a weakened interface between H2A-H2B dimers
      and the (H3-H4)2 tetramer, as well as between dimers and DNA. These findings
      agree with the experimental observations of position and charge dependent
      decreased nucleosome stability induced by the introduced mutations. This work
      highlights the importance of the H2A alpha3 domain and suggests allosteric
      effects between this domain and the outer DNA gyre as well as the H3 N-terminal
      tail.

PMID- 29038502
TI  - Three-dimensional Layered Water-Soluble Cellulose Acetate/Polyacrylamide
      Composites with Ultrahigh Ductility and Stretchability.
AB  - Water-soluble cellulose acetate (WSCA), one of the most important cellulose
      derivatives, possesses biocompatibility, biodegradability and broad chemical
      modifying capacities. In this work, highly polymerized WSCA was firstly
      synthesized and used as cross-linker to fabricate highly ductile, tough and
      resilient WSCA/polyacrylamide (PAM) composite hydrogels. The results showed that
      the WSCA/PAM nanocomposite hydrogels exhibited extraordinary toughness and
      ductility with a tensile strength of 297 kPa and elongation at break of about
      4020%. The enhancement of mechanical properties and stretchability were due to
      the synergistic effect from the hydrogen bonding and physical entanglement
      between the composite matrixes. Under stretching conditions, hydrogen bonds and
      the dense entanglement between WSCA chains and PAM could dynamically break and
      rearrange to dissipate energy. At the same time, the filaments of PAM embedded in
      layered WSCA matrix became unfolded or fractured to dissipate energy and
      maintained the conformation of hydrogels. It was envisioned that the introduction
      of WSCA into polymeric matrix would generate a facile method to fabricate
      multiple layered hybrid hydrogel network and significantly widen the WSCA
      applications in the preparation of high performance supramolecular systems.

PMID- 29038503
TI  - Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth
      of intestinal Enterococcus.
AB  - Chronic liver disease is rising in western countries and liver cirrhosis is the
      12th leading cause of death worldwide. Simultaneously, use of gastric acid
      suppressive medications is increasing. Here, we show that proton pump inhibitors
      promote progression of alcoholic liver disease, non-alcoholic fatty liver
      disease, and non-alcoholic steatohepatitis in mice by increasing numbers of
      intestinal Enterococcus spp. Translocating enterococci lead to hepatic
      inflammation and hepatocyte death. Expansion of intestinal Enterococcus faecalis
      is sufficient to exacerbate ethanol-induced liver disease in mice. Proton pump
      inhibitor use increases the risk of developing alcoholic liver disease among
      alcohol-dependent patients. Reduction of gastric acid secretion therefore appears
      to promote overgrowth of intestinal Enterococcus, which promotes liver disease,
      based on data from mouse models and humans. Recent increases in the use of
      gastric acid-suppressive medications might contribute to the increasing incidence
      of chronic liver disease.Proton pump inhibitors (PPIs) reduce gastric acid
      secretion and modulate gut microbiota composition. Here Llorente et al. show that
      PPIs induce bacterial overgrowth of enterococci, which, in turn, exacerbate
      ethanol-induced liver disease both in mice and humans.

PMID- 29038504
TI  - The contribution of Saccharomyces cerevisiae replicative age to the variations in
      the levels of Trx2p, Pdr5p, Can1p and Idh isoforms.
AB  - Asymmetrical division can be a reason for microbial populations heterogeneity. In
      particular, budding yeast daughter cells are more vulnerable to stresses than the
      mothers. It was suggested that yeast mother cells could also differ from each
      other depending on their replicative age. To test this, we measured the levels of
      Idh1-GFP, Idh2-GFP, Trx2-GFP, Pdr5-GFP and Can1-GFP proteins in cells of the few
      first, most represented, age cohorts. Pdr5p and Can1p were selected because of
      the pronounced mother-bud asymmetry for these proteins distributions, Trx2p as
      indicator of oxidative stress. Isocitrate dehydrogenase subunits Idh1p and Idh2p
      were assessed because their levels are regulated by mitochondria. We found a
      small negative correlation between yeast replicative age and Idh1-GFP or Idh2-GFP
      but not Trx2-GFP levels. Mitochondrial network fragmentation was also confirmed
      as an early event of replicative aging. No significant difference in the membrane
      proteins levels Pdr5p and Can1p was found. Moreover, the elder mother cells
      showed lower coefficient of variation for Pdr5p levels compared to the younger
      ones and the daughters. Our data suggest that the levels of stress-response
      proteins Pdr5p and Trx2p in the mother cells are stable during the first few cell
      cycles regardless of their mother-bud asymmetry.

PMID- 29038505
TI  - Punctate White Matter Lesions Associated With Altered Brain Development And
      Adverse Motor Outcome In Preterm Infants.
AB  - Preterm infants who develop neurodevelopmental impairment do not always have
      recognized abnormalities on cerebral ultrasound, a modality routinely used to
      assess prognosis. In a high proportion of infants, MRI detects punctate white
      matter lesions that are not seen on ultrasonography. To determine the relation of
      punctate lesions to brain development and early neurodevelopmental outcome we
      used multimodal brain MRI to study a large cohort of preterm infants. Punctate
      lesions without other focal cerebral or cerebellar lesions were detected at term
      equivalent age in 123 (24.3%) (59 male) of the 506 infants, predominantly in the
      centrum semiovale and corona radiata. Infants with lesions had higher gestational
      age, birth weight, and less chronic lung disease. Punctate lesions showed a dose
      dependent relation to abnormalities in white matter microstructure, assessed with
      tract-based spatial statistics, and reduced thalamic volume (p < 0.0001), and
      predicted unfavourable motor outcome at a median (range) corrected age of 20.2
      (18.4-26.3) months with sensitivity (95% confidence intervals) 71 (43-88) and
      specificity 72 (69-77). Punctate white matter lesions without associated cerebral
      lesions are common in preterm infants currently not regarded as at highest risk
      for cerebral injury, and are associated with widespread neuroanatomical
      abnormalities and adverse early neurodevelopmental outcome.

PMID- 29038506
TI  - Publisher Correction: Reassessing apoptosis in plants.
AB  - In the version of this Perspective originally published, the name of co-author
      Paul de Figueiredo was incorrect. This has now been corrected.

PMID- 29038507
TI  - Changes in brain metabolic connectivity underlie autistic-like social deficits in
      a rat model of autism spectrum disorder.
AB  - The neurobiological basis of social dysfunction and the high male prevalence in
      autism spectrum disorder (ASD) remain poorly understood. Although network
      alterations presumably underlie the development of autistic-like behaviors, a
      clear pattern of connectivity differences specific to ASD has not yet emerged.
      Because the heterogeneous nature of ASD hinders investigations in human subjects,
      we explored brain connectivity in an etiologically homogenous rat model of ASD
      induced by exposure to valproic acid (VPA) in utero. We performed partial
      correlation analysis of cross-sectional resting-state 18F-fluorodeoxyglucose
      positron emission tomography scans from VPA-exposed and control rats to estimate
      metabolic connectivity and conducted canonical correlation analysis of metabolic
      activity and behavior scores. VPA-treated rats exhibited impairments in social
      behaviors, and this difference was more pronounced in male than female rats.
      Similarly, current analyses revealed sex-specific changes in network connectivity
      and identified distinct alterations in the distributed metabolic activity
      patterns associated with autistic-like social deficits. Specifically, diminished
      activity in the salience network and enhanced activity in a cortico-cerebellar
      circuit correlated with the severity of social behavioral deficits. Such
      metabolic connectivity features may represent neurobiological substrates of
      autistic-like behavior, particularly in males, and may serve as a pathognomonic
      sign in the VPA rat model of ASD.

PMID- 29038509
TI  - Optimal [Formula: see text] -symmetric switch features exceptional point.
AB  - We consider the optimization problem of least energy-cost path in open systems
      that are described by non-Hermitian Hamiltonians. We apply it to find the optimal
      gain-loss profile for a non-uniform PT-symmetric coupler performing a binary
      transfer function. We bring evidence that the gain-loss profile fulfilling this
      requirement corresponds to a non-conventional situation where light intensity is
      conserved at every point along the PT-symmetric system. Besides, we find that the
      optimal profile corresponds to a practically important case of optical switching
      operation achieved with minimal amount of aggregate amplification level. We show
      that switching architectures using such type of gain-loss profiles are much more
      advantageous than conventional uniform PT-symmetric couplers in terms of gain and
      energy. Furthermore, this type of optimal profile turns out to be robust against
      fabrication imperfections. This opens new prospects for functional applications
      of PT-symmetric devices in photonics.

PMID- 29038508
TI  - Ottogi Inhibits Wnt/beta-catenin Signaling by Regulating Cell Membrane
      Trafficking of Frizzled8.
AB  - Wnt signaling controls critical developmental processes including tissue/body
      patterning. Here we report the identification of a novel regulator of Wnt
      signaling, OTTOGI (OTG), isolated from a large-scale expression screening of
      human cDNAs in zebrafish embryos. Overexpression of OTG in zebrafish embryos
      caused dorso-anteriorized phenotype, inhibited the expression of Wnt target
      genes, and prevented nuclear accumulation of beta-catenin. Conversely, knockdown
      of zebrafish otg using specific antisense morpholino promoted nuclear
      accumulation of beta-catenin and caused ventralization. However, OTG failed to
      rescue headless-like phenotype induced by inhibition of GSK-3beta activity,
      suggesting that OTG acts upstream of GSK-3beta. OTG bound specifically to
      Frizzled8 (Fz8) receptor and caused retention of Fz8 in the endoplasmic reticulum
      possibly by preventing N-linked glycosylation of Fz8. Taken together, our data
      indicate that OTG functions as a novel negative regulator of Wnt signaling during
      development by the modulation of cell surface expression of Fz receptor.

PMID- 29038510
TI  - Lure-and-Kill Yeast Interfering RNA Larvicides Targeting Neural Genes in the
      Human Disease Vector Mosquito Aedes aegypti.
AB  - New mosquito control strategies are vitally needed to address established
      arthropod-borne infectious diseases such as dengue and yellow fever and emerging
      diseases such as Zika and chikungunya, all of which are transmitted by the
      disease vector mosquito Aedes aegypti. In this investigation, Saccharomyces
      cerevisiae (baker's yeast) was engineered to produce short hairpin RNAs (shRNAs)
      corresponding to the Aedes aegypti orthologs of fasciculation and elongation
      protein zeta 2 (fez2) and leukocyte receptor cluster (lrc) member, two genes
      identified in a recent screen for A. aegypti larval lethal genes. Feeding A.
      aegypti with the engineered yeasts resulted in silenced target gene expression,
      disrupted neural development, and highly significant larval mortality. Larvicidal
      activities were retained following heat inactivation and drying of the yeast into
      tabular formulations that induced >95% mortality and were found to attract adult
      females to oviposit. These ready-to-use inactivated yeast interfering RNA tablets
      may one day facilitate the seamless integration of this new class of lure-and
      kill species-specific biorational mosquito larvicides into integrated mosquito
      control programs.

PMID- 29038511
TI  - Gene delivery of hypoxia-inducible VEGF targeting collagen effectively improves
      cardiac function after myocardial infarction.
AB  - Vascular endothelial growth factor (VEGF) plays important roles in improvement of
      cardiac function following myocardial infarction (MI). However, the lack of a
      steerable delivery system of VEGF targeting the infarcted myocardium reduces the
      therapeutic efficacy and safety. Here, we constructed a series of lentiviral
      vector systems which could express a fusion protein consisted of a collagen
      binding domain (CBD) and hVEGF (CBDhVEGF), under the control of 5HRE-hCMVmp
      (5HRE), the hypoxia-inducible promoter consists of five copies of the hypoxia
      responsive element (HRE) and a human cytomegalovirus minimal promoter (hCMVmp).
      We demonstrated that 5HRE has the comparable ability to strongly drive CBDhVEGF
      under hypoxic condition as the ubiquitous CMV promoter, but it can hardly drive
      target gene under normoxic condition. 5HRE-drived CBDhVEGF specifically bound to
      type I collagen and significantly promoted the viability of HUVEC cells.
      Moreover, after injection of lentivirus into heart of mouse with MI, CBDhVEGF was
      mainly retained in infarcted myocardium where containing rich collagen and
      significantly improved angiogenesis and cardiac function when compared with
      hVEGF. Moreover, CBDhVEGF mediated by lentivirus has little leakage from
      infarcted zone into blood than hVEGF. Taken together, our results indicate that
      5HRE-CBDhVEGF lentiviral vector system could improve cardiac function in the
      collagen-targeting and hypoxia-inducible manners.

PMID- 29038512
TI  - Levels of exhaled carbon monoxide measured during an intervention program predict
      1-year smoking cessation: a retrospective observational cohort study.
AB  - : Life-long smoking cessation is a critical public health objective, but it is
      difficult for numerous people. This study aimed to identify the independent
      predictors of 1-year abstinence in smokers motivated to quit and participating in
      an intervention program. This 6-year retrospective observational cohort study was
      conducted in smokers who participated in an intervention program. The exhaled
      carbon monoxide (CO) was sequentially measured on day 1, 8, 15, and 22 of the
      intervention program. The primary outcome measure was smoking status at 1 year of
      follow-up. A total of 162 participants were enrolled and divided into a
      successful quit group (n = 52) and unsuccessful quit group (n = 110). Using a
      multivariate logistic regression analysis, we reported that the intention to quit
      (adjusted odds ratio [AOR] = 1.475, 95% confidence interval [CI] = 1.169-1.862, P
      value = 0.001), varenicline use (AOR = 3.199, 95% CI = 1.290-7.934, P -value =
      0.012) and the exhaled CO level on day 8 (AOR = 0.937, 95% CI = 0.885-0.992, P
      value = 0.025) independently predicted 1-year smoking cessation. Moreover, the
      level of exhaled CO < 4.5 parts per million on day 8 significantly predict
      successful 1-year smoking cessation (area under curve 0.761, sensitivity 88.2%,
      and specificity 57.8%, P-value < 0.001). These independent predictors including
      intention to quit, varenicline use, and exhaled CO level on day 8, may help
      primary care physicians rearrange resources and refine the strategies for
      intervention programs to achieve a higher rate of long-term smoking cessation.
      QUITTING SMOKING: IDENTIFYING PREDICTORS OF SUCCESS: Researchers in Korea
      identify key predictors that pinpoint people most likely to quit smoking
      successfully during intervention programs. Millions are spent each year
      supporting people to quit smoking. However, successful quitters remain in the
      minority, with only 9-35 per cent of those in intervention programs abstaining
      for at least a year. Hsin-Kuo Ko at Taipei Veterans General Hospital and co
      workers identified key independent indicators of successful abstinence in 162
      smokers attending an intervention program. Alongside having a high intention to
      quit and using varenicline medication, a potential predictor is having an exhaled
      carbon monoxide (CO) level of less than 4.5 parts-per-million by day 8 of the
      course. Exhaled CO is higher in smokers than in non-smokers. Measuring CO levels
      one week into courses may be a useful biomarker to identify those fully committed
      to quit.

PMID- 29038513
TI  - Anomalous Kondo resonance mediated by semiconducting graphene nanoribbons in a
      molecular heterostructure.
AB  - Kondo resonances in heterostructures formed by magnetic molecules on a metal
      require free host electrons to interact with the molecular spin and create
      delicate many-body states. Unlike graphene, semiconducting graphene nanoribbons
      do not have free electrons due to their large bandgaps, and thus they should
      electronically decouple molecules from the metal substrate. Here, we observe
      unusually well-defined Kondo resonances in magnetic molecules separated from a
      gold surface by graphene nanoribbons in vertically stacked heterostructures.
      Surprisingly, the strengths of Kondo resonances for the molecules on graphene
      nanoribbons appear nearly identical to those directly adsorbed on the top, bridge
      and threefold hollow sites of Au(111). This unexpectedly strong spin-coupling
      effect is further confirmed by density functional calculations that reveal no
      spin-electron interactions at this molecule-gold substrate separation if the
      graphene nanoribbons are absent. Our findings suggest graphene nanoribbons
      mediate effective spin coupling, opening a way for potential applications in
      spintronics.Semiconducting graphene nanoribbon provides a platform for band-gap
      engineering desired for electronic and optoelectronic applications. Here, Li et
      al. show that graphene nanoribbon can effectively mediate the interaction of
      molecular magnetic moment and electronic spin in underlying metallic substrates.

PMID- 29038515
TI  - Molecular Tilting Alignment on Ag@C Nanocubes Monitored by Temperature-Dependent
      Surface Enhanced Raman Scattering.
AB  - Core@shell Ag@C nanocubes (NCs) with a cubic silver core (~60 nm of side length)
      and a coating of ultrathin amorphous carbon (~4 nm) have been synthesized on a
      large scale by a one-pot hydrothermal method. The carbon layer not only protects
      the Ag@C nanocubes from oxidation under hydrothermal condition, but also
      stabilizes the structure of Ag cores. Considering that optical properties of
      nanostructured metals strongly depend on the temperature for SERS measurement, in
      this work we systemically investigate the relationship between the orientation of
      molecules adsorbed on Ag@C NCs and temperature by SERS spectra. Results suggest
      that the adsorbed 4-MBA molecules prefer a flat orientation on the NC surface
      with temperature decreasing. In addition, Ag@C NCs after one-year storage in
      water still maintain high SERS-active capability. Our synthesized Ag@C NCs with
      excellent and stable optical properties can be potentially applied in the field
      of sensor and ultrasensitive spectral analysis.

PMID- 29038514
TI  - Extensive gain and loss of photosystem I subunits in chromerid algae,
      photosynthetic relatives of apicomplexans.
AB  - In oxygenic photosynthesis the initial photochemical processes are carried out by
      photosystem I (PSI) and II (PSII). Although subunit composition varies between
      cyanobacterial and plastid photosystems, the core structures of PSI and PSII are
      conserved throughout photosynthetic eukaryotes. So far, the photosynthetic
      complexes have been characterised in only a small number of organisms. We
      performed in silico and biochemical studies to explore the organization and
      evolution of the photosynthetic apparatus in the chromerids Chromera velia and
      Vitrella brassicaformis, autotrophic relatives of apicomplexans. We catalogued
      the presence and location of genes coding for conserved subunits of the
      photosystems as well as cytochrome b6f and ATP synthase in chromerids and other
      phototrophs and performed a phylogenetic analysis. We then characterised the
      photosynthetic complexes of Chromera and Vitrella using 2D gels combined with
      mass-spectrometry and further analysed the purified Chromera PSI. Our data
      suggest that the photosynthetic apparatus of chromerids underwent unique
      structural changes. Both photosystems (as well as cytochrome b6f and ATP
      synthase) lost several canonical subunits, while PSI gained one superoxide
      dismutase (Vitrella) or two superoxide dismutases and several unknown proteins
      (Chromera) as new regular subunits. We discuss these results in light of the
      extraordinarily efficient photosynthetic processes described in Chromera.

PMID- 29038517
TI  - Interplay between the gold nanoparticle sub-cellular localization, size, and the
      photon energy for radiosensitization.
AB  - There are large variations in the reported efficiency of gold nanoparticle (GNP)
      radiosensitization. We have previously reported on a predictive model, which
      accounts for the detailed Auger and photoelectron tracks to calculate the cell
      survival probability. After validating our model using PC-3 cells incubated with
      2 mg/ml of 30 nm GNPs and irradiated with 100 kVp or 300 kVp beams, we evaluated
      the interplay between photon energy, GNP size (1.9 and 100 nm) and sub-cellular
      localization. Experiments were in excellent agreement with the model. In
      predictive modeling, using a 100 kVp source and 1.9 nm nanoparticles, GNP
      localization had a significant impact on cell survival. A sensitizer enhancement
      ratio of 1.34 was achieved when GNPs were localized outside the cells, increasing
      to 2.56 when GNPs were also distributed in the cytoplasm and nucleus. Using a 300
      kVp source, which emits photons mainly above the gold K-edge, the dependence on
      GNP localization and size was barely detectable, since long ranged electrons
      dominate the energy deposition. In summary, achieving intracellular uptake with
      targeted-GNPs can significantly enhance radiosensitization for photon energies
      below the gold K-edge, where Auger electrons contribute significantly to the
      local energy deposition. For higher energies, this is much less important.

PMID- 29038516
TI  - EEG topographies provide subject-specific correlates of motor control.
AB  - Electroencephalography (EEG) of brain activity can be represented in terms of
      dynamically changing topographies (microstates). Notably, spontaneous brain
      activity recorded at rest can be characterized by four distinctive topographies.
      Despite their well-established role during resting state, their implication in
      the generation of motor behavior is debated. Evidence of such a functional role
      of spontaneous brain activity would provide support for the design of novel and
      sensitive biomarkers in neurological disorders. Here we examined whether and to
      what extent intrinsic brain activity contributes and plays a functional role
      during natural motor behaviors. For this we first extracted subject-specific EEG
      microstates and muscle synergies during reaching-and-grasping movements in
      healthy volunteers. We show that, in every subject, well-known resting-state
      microstates persist during movement execution with similar topographies and
      temporal characteristics, but are supplemented by novel task-related microstates.
      We then show that the subject-specific microstates' dynamical organization
      correlates with the activation of muscle synergies and can be used to decode
      individual grasping movements with high accuracy. These findings provide first
      evidence that spontaneous brain activity encodes detailed information about motor
      control, offering as such the prospect of a novel tool for the definition of
      subject-specific biomarkers of brain plasticity and recovery in neuro-motor
      disorders.

PMID- 29038518
TI  - Direct measurement of discrete valley and orbital quantum numbers in bilayer
      graphene.
AB  - The high magnetic field electronic structure of bilayer graphene is enhanced by
      the spin, valley isospin, and an accidental orbital degeneracy, leading to a
      complex phase diagram of broken symmetry states. Here, we present a technique for
      measuring the layer-resolved charge density, from which we directly determine the
      valley and orbital polarization within the zero energy Landau level. Layer
      polarization evolves in discrete steps across 32 electric field-tuned phase
      transitions between states of different valley, spin, and orbital order,
      including previously unobserved orbitally polarized states stabilized by skew
      interlayer hopping. We fit our data to a model that captures both single-particle
      and interaction-induced anisotropies, providing a complete picture of this
      correlated electron system. The resulting roadmap to symmetry breaking paves the
      way for deterministic engineering of fractional quantum Hall states, while our
      layer-resolved technique is readily extendable to other two-dimensional materials
      where layer polarization maps to the valley or spin quantum numbers.The phase
      diagram of bilayer graphene at high magnetic fields has been an outstanding
      question, with orders possibly between multiple internal quantum degrees of
      freedom. Here, Hunt et al. report the measurement of the valley and orbital
      order, allowing them to directly reconstruct the phase diagram.

PMID- 29038519
TI  - Resveratrol therapeutics combines both antimicrobial and immunomodulatory
      properties against respiratory infection by nontypeable Haemophilus influenzae.
AB  - The respiratory pathogen nontypeable Haemophilus influenzae (NTHi) is an
      important cause of acute exacerbation of chronic obstructive pulmonary disease
      (AECOPD) that requires efficient treatments. A previous screening for host genes
      differentially expressed upon NTHi infection identified sirtuin-1, which encodes
      a NAD-dependent deacetylase protective against emphysema and is activated by
      resveratrol. This polyphenol concomitantly reduces NTHi viability, therefore
      highlighting its therapeutic potential against NTHi infection at the COPD airway.
      In this study, resveratrol antimicrobial effect on NTHi was shown to be
      bacteriostatic and did not induce resistance development in vitro. Analysis of
      modulatory properties on the NTHi-host airway epithelial interplay showed that
      resveratrol modulates bacterial invasion but not subcellular location, reduces
      inflammation without targeting phosphodiesterase 4B gene expression, and dampens
      beta defensin-2 gene expression in infected cells. Moreover, resveratrol
      therapeutics against NTHi was evaluated in vivo on mouse respiratory and
      zebrafish septicemia infection model systems, showing to decrease NTHi viability
      in a dose-dependent manner and reduce airway inflammation upon infection, and to
      have a significant bacterial clearing effect without signs of host toxicity,
      respectively. This study presents resveratrol as a therapeutic of particular
      translational significance due to the attractiveness of targeting both infection
      and overactive inflammation at the COPD airway.

PMID- 29038520
TI  - Decrypting Strong and Weak Single-Walled Carbon Nanotubes Interactions with
      Mitochondrial Voltage-Dependent Anion Channels Using Molecular Docking and
      Perturbation Theory.
AB  - The current molecular docking study provided the Free Energy of Binding (FEB) for
      the interaction (nanotoxicity) between VDAC mitochondrial channels of three
      species (VDAC1-Mus musculus, VDAC1-Homo sapiens, VDAC2-Danio rerio) with SWCNT-H,
      SWCNT-OH, SWCNT-COOH carbon nanotubes. The general results showed that the FEB
      values were statistically more negative (p < 0.05) in the following order: (SWCNT
      VDAC2-Danio rerio) > (SWCNT-VDAC1-Mus musculus) > (SWCNT-VDAC1-Homo sapiens) >
      (ATP-VDAC). More negative FEB values for SWCNT-COOH and OH were found in VDAC2
      Danio rerio when compared with VDAC1-Mus musculus and VDAC1-Homo sapiens (p <
      0.05). In addition, a significant correlation (0.66 > r2 > 0.97) was observed
      between n-Hamada index and VDAC nanotoxicity (or FEB) for the zigzag topologies
      of SWCNT-COOH and SWCNT-OH. Predictive Nanoparticles-Quantitative-Structure
      Binding-Relationship models (nano-QSBR) for strong and weak SWCNT-VDAC docking
      interactions were performed using Perturbation Theory, regression and
      classification models. Thus, 405 SWCNT-VDAC interactions were predicted using a
      nano-PT-QSBR classifications model with high accuracy, specificity, and
      sensitivity (73-98%) in training and validation series, and a maximum AUROC value
      of 0.978. In addition, the best regression model was obtained with Random Forest
      (R2 of 0.833, RMSE of 0.0844), suggesting an excellent potential to predict SWCNT
      VDAC channel nanotoxicity. All study data are available at
      https://doi.org/10.6084/m9.figshare.4802320.v2 .

PMID- 29038521
TI  - PKCepsilon phosphorylates MIIP and promotes colorectal cancer metastasis through
      inhibition of RelA deacetylation.
AB  - EGFR signaling is implicated in NF-kappaB activation. However, the concrete
      mechanisms by which the core transducer of NF-kappaB signaling pathway, RelA/p65
      is regulated under EGFR activation remains to be further clarified. Here, we show
      that EGF stimulation induces PKCepsilon-dependent phosphorylation of migration
      and invasion inhibitory protein (MIIP) at Ser303; this phosphorylation promotes
      the interaction between MIIP and RelA in the nucleus, by which MIIP prevents
      histone deacetylase 6 (HDAC6)-mediated RelA deacetylation, and thus enhances
      transcriptional activity of RelA and facilitates tumor metastasis. Meanwhile PP1,
      which functions as a phosphatase, is found to mediate MIIP-S303 dephosphorylation
      and its expression level inversely correlates with metastatic capability of tumor
      cells. Moreover, clinical analyses indicate the level of MIIP-S303
      phosphorylation correlates with colorectal cancer (CRC) metastasis and prognosis.
      These findings uncover an unidentified mechanism underlying the precise
      regulation of NF-kappaB by EGF, and highlight the critical role of nuclear MIIP
      in tumor metastasis.In colorectal cancer, EGFR signalling is implicated in
      metastasis. Here, the authors unravel a mechanism through which EGF stimulation
      induces MIIP phosphorylation, leading to MIIP interacting with RelA-this prevents
      RelA deactylation and enhances transcriptional activity, facilitating metastasis.

PMID- 29038522
TI  - Ecological resilience in lakes and the conjunction fallacy.
AB  - There is a pressing need to apply stability and resilience theory to
      environmental management to restore degraded ecosystems effectively and to
      mitigate the effects of impending environmental change. Lakes represent excellent
      model case studies in this respect and have been used widely to demonstrate
      theories of ecological stability and resilience that are needed to underpin
      preventative management approaches. However, we argue that this approach is not
      yet fully developed because the pursuit of empirical evidence to underpin such
      theoretically grounded management continues in the absence of an objective
      probability framework. This has blurred the lines between intuitive logic (based
      on the elementary principles of probability) and extensional logic (based on
      assumption and belief) in this field.

PMID- 29038523
TI  - Angiotensin II type 2 receptor (AT2R) as a novel modulator of inflammation in
      rheumatoid arthritis synovium.
AB  - Despite increasing evidence suggesting that angiotensin II type 2 receptor (AT2R)
      may regulate tissue inflammation, no study has yet analyzed its possible
      implication in rheumatoid arthritis (RA) synovitis. In this study, we
      investigated the expression and function of AT2R in synovial tissue and cultured
      fibroblast-like synoviocytes (FLS) from RA patients. AT2R expression was strongly
      increased in RA compared with osteoarthritis (OA) synovium, as well as in in
      cultured RA-FLS respect to OA-FLS and healthy FLS. Treatment with pro
      inflammatory cytokines was able not only to boost AT2R expression in RA-FLS and
      OA-FLS, but also to induce its de novo expression in healthy FLS. The stimulation
      of AT2R with the specific agonist CGP42112A significantly reduced gene expression
      of interleukin (IL)-1beta and IL-6 and activation of NF-kappaB in RA-FLS, while
      opposite effects were elicited by AT2R small interfering RNA. Moreover, AT2R
      agonism efficiently decreased RA-FLS proliferation and migration either at
      baseline or under pro-inflammatory cytokine challenge. In conclusion, AT2R is
      strongly expressed in key effector cells of rheumatoid synovitis, namely RA-FLS,
      and the activation of AT2R with a specific agonist may effectively dampen their
      pro-inflammatory and aggressive behavior. AT2R agonism might represent a novel
      therapeutic strategy for patients with RA.

PMID- 29038524
TI  - RNA-Seq transcriptome profiling of mouse oocytes after in vitro maturation and/or
      vitrification.
AB  - In vitro maturation (IVM) and vitrification have been widely used to prepare
      oocytes before fertilization; however, potential effects of these procedures,
      such as expression profile changes, are poorly understood. In this study, mouse
      oocytes were divided into four groups and subjected to combinations of in vitro
      maturation and/or vitrification treatments. RNA-seq and in silico pathway
      analysis were used to identify differentially expressed genes (DEGs) that may be
      involved in oocyte viability after in vitro maturation and/or vitrification. Our
      results showed that 1) 69 genes were differentially expressed after IVM, 66 of
      which were up-regulated. Atp5e and Atp5o were enriched in the most significant
      gene ontology term "mitochondrial membrane part"; thus, these genes may be
      promising candidate biomarkers for oocyte viability after IVM. 2) The influence
      of vitrification on the transcriptome of oocytes was negligible, as no DEGs were
      found between vitrified and fresh oocytes. 3) The MII stage is more suitable for
      oocyte vitrification with respect to the transcriptome. This study provides a
      valuable new theoretical basis to further improve the efficiency of in vitro
      maturation and/or oocyte vitrification.

PMID- 29038525
TI  - Elevated serum alkaline phosphatase and cardiovascular or all-cause mortality
      risk in dialysis patients: A meta-analysis.
AB  - Studies on serum alkaline phosphatase (ALP) and mortality risk in patients with
      end-stage renal disease (ESRD) undergoing dialysis have yielded conflicting
      results. This meta-analysis was designed to assess the association of serum ALP
      levels with cardiovascular or all-cause mortality risk among patients on
      dialysis. PubMed and Embase databases were searched until March 2017 for studies
      evaluating the association of serum ALP levels and cardiovascular or all-cause
      mortality risk in adult patients with ESRD undergoing maintenance hemodialysis or
      chronic peritoneal dialysis. Twelve studies enrolling 393,200 patients on
      dialysis were included. Compared with the reference low serum ALP category,
      pooled adjusted hazard risk (HR) of all-cause mortality was 1.46 (95% confidence
      interval [CI] 1.30-1.65) for patients on hemodialysis and 1.93 (95% CI 1.71-2.17)
      for peritoneal patients on dialysis. In addition, elevated serum ALP
      significantly increased cardiovascular mortality among patients on peritoneal
      dialysis (HR 2.39; 95% CI 1.23-4.65) but not in patients on hemodialysis (HR
      1.08; 95% CI 0.84-1.40). Elevated serum ALP was an independent risk factor for
      all-cause mortality among patients on hemodialysis or peritoneal dialysis.
      Further well-designed prospective studies are needed to investigate the
      association of high serum ALP levels with cardiovascular mortality among patients
      on dialysis.

PMID- 29038526
TI  - Strain in shock-loaded skeletal muscle and the time scale of muscular wobbling
      mass dynamics.
AB  - In terrestrial locomotion, muscles undergo damped oscillations in response to
      limb impacts with the ground. Muscles are also actuators that generate mechanical
      power to allow locomotion. The corresponding elementary contractile process is
      the work stroke of an actin-myosin cross-bridge, which may be forcibly detached
      by superposed oscillations. By experimentally emulating rat leg impacts, we found
      that full activity and non-fatigue must meet to possibly prevent forcible cross
      bridge detachment. Because submaximal muscle force represents the ordinary
      locomotor condition, our results show that forcible, eccentric cross-bridge
      detachment is a common, physiological process even during isometric muscle
      contractions. We also calculated the stiffnesses of the whole muscle-tendon
      complex and the fibre material separately, as well as Young's modulus of the
      latter: 1.8 MPa and 0.75 MPa for fresh, fully active and passive fibres,
      respectively. Our inferred Young's modulus of the tendon-aponeurosis complex
      suggests that stiffness in series to the fibre material is determined by the
      elastic properties of the aponeurosis region, rather than the tendon material.
      Knowing these stiffnesses and the muscle mass, the complex' eigenfrequency for
      responses to impacts can be quantified, as well as the size-dependency of this
      time scale of muscular wobbling mass dynamics.

PMID- 29038528
TI  - Transcriptome analysis of Spodoptera frugiperda Sf9 cells reveals putative
      apoptosis-related genes and a preliminary apoptosis mechanism induced by
      azadirachtin.
AB  - As an important botanical pesticide, azadirachtin demonstrates broad insecticidal
      activity against many agricultural pests. The results of a previous study
      indicated the toxicity and apoptosis induction of azadirachtin in Spodoptera
      frugiperda Sf9 cells. However, the lack of genomic data has hindered a deeper
      investigation of apoptosis in Sf9 cells at a molecular level. In the present
      study, the complete transcriptome data for Sf9 cell line was accomplished using
      Illumina sequencing technology, and 97 putative apoptosis-related genes were
      identified through BLAST and KEGG orthologue annotations. Fragments of potential
      candidate apoptosis-related genes were cloned, and the mRNA expression patterns
      of ten identified genes regulated by azadirachtin were examined using qRT-PCR.
      Furthermore, Western blot analysis showed that six putative apoptosis-related
      proteins were upregulated after being treated with azadirachtin while the protein
      Bcl-2 were downregulated. These data suggested that both intrinsic and extrinsic
      apoptotic signal pathways comprising the identified potential apoptosis-related
      genes were potentially active in S. frugiperda. In addition, the preliminary
      results revealed that caspase-dependent or caspase-independent apoptotic pathways
      could function in azadirachtin-induced apoptosis in Sf9 cells.

PMID- 29038529
TI  - Hybrid structure of white layer in high carbon steel - Formation mechanism and
      its properties.
AB  - This study identifies for the first time, the hybrid structure of the white layer
      in high carbon steel and describes its formation mechanism and properties. The so
      called 'white layer' in steel forms during high strain rate deformation and
      appears featureless under optical microscopy. While many researchers have
      investigated the formation of the white layer, there has been no definitive
      study, nor is there sufficient evidence to fully explain the formation, structure
      and properties of the layer. In this study, the formation, morphology and
      mechanical properties of the white layer was determined following impact testing,
      using a combination of optical and SE- microscopy, HR-EBSD, TKD and TEM as well
      as nano-indentation hardness measurements and FE modelling. The phase
      transformation and recrystallization within and near the white layer was also
      investigated. The microstructure of the steel in the white layer consisted of
      nano-sized grains of martensite. A very thin layer of austenite with nano sized
      grains was identified within the white layer by HR-EBSD techniques, the presence
      of which is attributed to a thermally-induced reverse phase transformation.
      Overall, the combination of phase transformations, strain hardening and grain
      refinement led to a hybrid structure and an increase in hardness of the white
      layer.

PMID- 29038527
TI  - Blood vessel control of macrophage maturation promotes arteriogenesis in
      ischemia.
AB  - Ischemia causes an inflammatory response that is intended to restore perfusion
      and homeostasis yet often aggravates damage. Here we show, using conditional
      genetic deletion strategies together with adoptive cell transfer experiments in a
      mouse model of hind limb ischemia, that blood vessels control macrophage
      differentiation and maturation from recruited monocytes via Notch signaling,
      which in turn promotes arteriogenesis and tissue repair. Macrophage maturation is
      controlled by Notch ligand Dll1 expressed in vascular endothelial cells of
      arteries and requires macrophage canonical Notch signaling via Rbpj, which
      simultaneously suppresses an inflammatory macrophage fate. Conversely,
      conditional mutant mice lacking Dll1 or Rbpj show proliferation and transient
      accumulation of inflammatory macrophages, which antagonizes arteriogenesis and
      tissue repair. Furthermore, the effects of Notch are sufficient to generate
      mature macrophages from monocytes ex vivo that display a stable anti-inflammatory
      phenotype when challenged with pro-inflammatory stimuli. Thus, angiocrine Notch
      signaling fosters macrophage maturation during ischemia.Molecular mechanisms of
      macrophage-mediated regulation of artery growth in response to ischemia are
      poorly understood. Here the authors show that vascular endothelium controls
      macrophage maturation and differentiation via Notch signaling, which in turn
      promotes arteriogenesis and ischemic tissue recovery.

PMID- 29038530
TI  - Collision with duplex DNA renders Escherichia coli DNA polymerase III holoenzyme
      susceptible to DNA polymerase IV-mediated polymerase switching on the sliding
      clamp.
AB  - Organisms possess multiple DNA polymerases (Pols) and use each for a different
      purpose. One of the five Pols in Escherichia coli, DNA polymerase IV (Pol IV),
      encoded by the dinB gene, is known to participate in lesion bypass at certain DNA
      adducts. To understand how cells choose Pols when the replication fork encounters
      an obstacle on template DNA, the process of polymerase exchange from the primary
      replicative enzyme DNA polymerase III (Pol III) to Pol IV was studied in vitro.
      Replicating Pol III forming a tight holoenzyme (Pol III HE) with the sliding
      clamp was challenged by Pol IV on a primed ssDNA template carrying a short
      inverted repeat. A rapid and lesion-independent switch from Pol III to Pol IV
      occurred when Pol III HE encountered a hairpin stem duplex, implying that the
      loss of Pol III-ssDNA contact induces switching to Pol IV. Supporting this idea,
      mutant Pol III with an increased affinity for ssDNA was more resistant to Pol IV
      than wild-type Pol III was. We observed that an exchange between Pol III and Pol
      IV also occurred when Pol III HE collided with primer/template duplex. Our data
      suggest that Pol III-ssDNA interaction may modulate the susceptibility of Pol III
      HE to Pol IV-mediated polymerase exchange.

PMID- 29038533
TI  - Video capillaroscopy clarifies mechanism of the photoplethysmographic waveform
      appearance.
AB  - Photoplethysmography (PPG) devices are widely used in clinical practice but the
      origin of PPG signal is still under debating. The classical theory assumes that
      the PPG waveform stems from variations of blood volume in pulsating arteries. In
      this research we analysed high-speed video recordings of capillaries in a
      fingernail bed. It was found that speed of erythrocytes in capillaries has
      pronounced modulation in time, which follows variations of instantaneous blood
      pressure in arteries. However, the mean speed significantly differs even for
      neighbour capillaries whereas change of the speed occurs in phase for the most of
      capillaries. Moreover, the light intensity remitted from the papillary dermis is
      also modulated at the heartbeat frequency displaying significant correlation with
      waveforms of the RBC speed. Obtained results can hardly be explained by the
      classical theory of PPG signal formation. Shallow penetrating visible light
      acquires modulation of erythrocytes density in the capillary bed without
      interacting with deeper situated pulsating arteries. Therefore, the capillary bed
      could serve as a distributed sensor for monitor the status of deep vessels.
      Better understanding of the photoplethysmography basis will result in a wider
      range of applications of this fast growing technology in both medical and
      research practice.

PMID- 29038531
TI  - TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142
      3p.
AB  - Recent evidence suggests that the ion channel TRPA1 is implicated in lung
      adenocarcinoma (LUAD), where its role and mechanism of action remain unknown. We
      have previously established that the membrane receptor FGFR2 drives LUAD
      progression through aberrant protein-protein interactions mediated via its C
      terminal proline-rich motif. Here we report that the N-terminal ankyrin repeats
      of TRPA1 directly bind to the C-terminal proline-rich motif of FGFR2 inducing the
      constitutive activation of the receptor, thereby prompting LUAD progression and
      metastasis. Furthermore, we show that upon metastasis to the brain, TRPA1 gets
      depleted, an effect triggered by the transfer of TRPA1-targeting exosomal
      microRNA (miRNA-142-3p) from brain astrocytes to cancer cells. This
      downregulation, in turn, inhibits TRPA1-mediated activation of FGFR2, hindering
      the metastatic process. Our study reveals a direct binding event and
      characterizes the role of TRPA1 ankyrin repeats in regulating FGFR2-driven
      oncogenic process; a mechanism that is hindered by miRNA-142-3p.TRPA1 has been
      reported to contribute lung cancer adenocarcinoma (LUAD), but the mechanisms are
      unclear. Here the authors propose that TRPA1/FGFR2 interaction is functional in
      LUAD and show that astrocytes oppose brain metastasis by mediating the
      downregulation of TRPA1 through exosome-delivered miRNA-142-3p.

PMID- 29038532
TI  - The major outer sheath protein forms distinct conformers and multimeric complexes
      in the outer membrane and periplasm of Treponema denticola.
AB  - The major outer sheath protein (MOSP) is a prominent constituent of the cell
      envelope of Treponema denticola (TDE) and one of its principal virulence
      determinants. Bioinformatics predicts that MOSP consists of N- and C-terminal
      domains, MOSPN and MOSPC. Biophysical analysis of constructs refolded in vitro
      demonstrated that MOSPC, previously shown to possess porin activity, forms
      amphiphilic trimers, while MOSPN forms an extended hydrophilic monomer. In TDE
      and E. coli expressing MOSP with a PelB signal sequence (PelB-MOSP), MOSPC is OM
      embedded and surface-exposed, while MOSPN resides in the periplasm.
      Immunofluorescence assay, surface proteolysis, and novel cell fractionation
      schemes revealed that MOSP in TDE exists as outer membrane (OM) and periplasmic
      trimeric conformers; PelB-MOSP, in contrast, formed only OM-MOSP trimers.
      Although both conformers form hetero-oligomeric complexes in TDE, only OM-MOSP
      associates with dentilisin. Mass spectrometry (MS) indicated that OM-MOSP
      interacts with proteins in addition to dentilisin, most notably, oligopeptide
      binding proteins (OBPs) and the beta-barrel of BamA. MS also identified candidate
      partners for periplasmic MOSP, including TDE1658, a spirochete-specific SurA/PrsA
      ortholog. Collectively, our data suggest that MOSP destined for the TDE OM
      follows the canonical BAM pathway, while formation of a stable periplasmic
      conformer involves an export-related, folding pathway not present in E. coli.

PMID- 29038535
TI  - Investigating spatiotemporal changes of the land-surface processes in Xinjiang
      using high-resolution CLM3.5 and CLDAS: Soil temperature.
AB  - Soil temperature plays a key role in the land surface processes because this
      parameter affects a series of physical, chemical, and biological processes in the
      soil, such as water and heat fluxes. However, observation of soil temperature is
      quite limited, especially at the regional scale. Therefore, this study is to
      investigate the spatiotemporal features of soil temperature in Xinjiang, China,
      using the Community Land model 3.5 (CLM3.5) with the atmospheric near-surface
      forcing data of the China Meteorological Administration Land Data Assimilation
      System (CLDAS). We use the observed soil temperature data collected from 105
      national automatic stations during 2009 through 2012 in the study area to verify
      the simulation capability. The comparison results indicate that the CLM3.5 with
      the CLDAS driving field could well simulate the spatiotemporal patterns of the
      soil temperature at hourly, daily, and monthly time scales and at three depths (5
      cm, 20 cm, and 80 cm). We also produce a soil temperature database of the region
      that is continuous both in time and space with high resolution (about 6.25 km).
      Overall, this study could help understand the regional and vertical
      characteristics of the soil temperature and provide an important scientific basis
      for other land-surface processes.

PMID- 29038534
TI  - Performance and consistency of a fluorescence-based high-throughput screening
      assay for use in Babesia drug screening in mice.
AB  - In this study, we evaluated the validity of a fluorescence-based assay using SYBR
      Green I (SG I) stain for screening antibabesial compounds against B. microti in
      mice. Two different hematocrits (HCTs; 2.5% and 5%) were used. Correlating
      relative fluorescence units (RFUs) with parasitemia showed significant linear
      relationships with R2 values of 0.97 and 0.99 at HCTs of 2.5% and 5%,
      respectively. Meanwhile, the Z' factors in a high-throughput screening (HTS)
      assay were within the permissible limit (>=0.5) at 2.5% HCT and lower than this
      value at 5% HCT. Taken together, the highest signal-to-noise (S/N) ratios were
      obtained at 2.5% HCT; therefore, we concluded that 2.5% was the best HCT for
      applying fluorescence assay in antibabesial drug screening in mice. Additionally,
      positive control mice and those treated with diminazene aceturate, pyronaridine
      tetraphosphate, and an allicin/diminazene aceturate combination showed peak
      parasitemia and fluorescence values on the same day post-inoculation. Moreover,
      using different concentrations of SG I revealed that the optimal concentration
      was 2x. In summary, considering that all experiments were applied under optimal
      laboratory conditions, fluorescence assay at 2.5% HCT using 2x SG I for B.
      microti parasite offers a novel approach for drug screening in mice.

PMID- 29038536
TI  - Hydrogen Sulphide Treatment Increases Insulin Sensitivity and Improves Oxidant
      Metabolism through the CaMKKbeta-AMPK Pathway in PA-Induced IR C2C12 Cells.
AB  - Studies have reported attenuation of insulin resistance (IR) by improving
      phosphorylation of the insulin signalling pathway. However, the upstream
      molecular signalling pathway is still elusive. In this study, Western blot was
      used to evaluate the phosphorylation level of the insulin signalling pathway and
      the AMPK pathway. 2-NBDG was used to evaluate glucose uptake. Ca2+ imaging was
      used to assess change of intracellular Ca2+ concentration. We found that NaHS
      enhanced the intracellular Ca2+ concentration and glucose uptake and activated
      the insulin signalling cascade in a palmitic acid (PA)-induced IR model in C2C12
      cells. Furthermore, activation of the IRS1/PI3K/AKT pathway and glucose uptake
      were decreased when AMPK or CaMKKbeta was inhibited. Our study also showed that
      the mitochondrial electron transport chain, ATP production, and
      intramitochondrial cAMP declined in the IR model but that this effect was
      reversed by NaHS, an effect that may be mediated by the Ca2+/CaMKK2/AMPK and
      PI3K/AKT pathways. Our data indicate that H2S improves activation of the insulin
      signalling cascade and glucose uptake via activation of the Ca2+/CaMKK2/AMPK
      pathway and mitochondrial metabolism in C2C12 cells. Furthermore, NaHS protects
      mitochondrial function and maintains normal ATP production by activating the cAMP
      system and the Ca2+/CaMKK2/AMPK and PI3K/ATK pathways.

PMID- 29038537
TI  - B cells in type 1 diabetes mellitus and diabetic kidney disease.
AB  - Type 1 diabetes mellitus (T1DM) is an autoimmune disorder that affects an
      estimated 30 million people worldwide. It is characterized by the destruction of
      pancreatic beta cells by the immune system, which leads to lifelong dependency on
      exogenous insulin and imposes an enormous burden on patients and health-care
      resources. T1DM is also associated with an increased risk of comorbidities, such
      as cardiovascular disease, retinopathy, and diabetic kidney disease (DKD),
      further contributing to the burden of this disease. Although T cells are largely
      considered to be responsible for beta-cell destruction in T1DM, increasing
      evidence points towards a role for B cells in disease pathogenesis. B cell
      depletion, for example, delays disease progression in patients with newly
      diagnosed T1DM. Loss of tolerance of islet antigen-reactive B cells occurs early
      in disease and numbers of pancreatic CD20+ B cells correlate with beta-cell loss.
      Although the importance of B cells in T1DM is increasingly apparent, exactly how
      these cells contribute to disease and its comorbidities, such as DKD, is not well
      understood. Here we discuss the role of B cells in the pathogenesis of T1DM and
      how these cells are activated during disease development. Finally, we speculate
      on how B cells might contribute to the development of DKD.

PMID- 29038538
TI  - Correlated states in beta-Li2IrO3 driven by applied magnetic fields.
AB  - Magnetic honeycomb iridates are thought to show strongly spin-anisotropic
      exchange interactions which, when highly frustrated, lead to an exotic state of
      matter known as the Kitaev quantum spin liquid. However, in all known examples
      these materials magnetically order at finite temperatures, the scale of which may
      imply weak frustration. Here we show that the application of a relatively small
      magnetic field drives the three-dimensional magnet beta-Li2IrO3 from its
      incommensurate ground state into a quantum correlated paramagnet. Interestingly,
      this paramagnetic state admixes a zig-zag spin mode analogous to the zig-zag
      order seen in other Mott-Kitaev compounds. The rapid onset of the field-induced
      correlated state implies the exchange interactions are delicately balanced,
      leading to strong frustration and a near degeneracy of different ground
      states.Materials with a Kitaev spin liquid ground state are sought after as
      models of quantum phases but candidates so far form either zig-zag or
      incommensurate magnetic order. Ruiz et al. find a crossover between these states
      in beta-Li2IrO3 under weak magnetic fields, indicating strongly frustrated spin
      interactions.

PMID- 29038539
TI  - Electro-osmotic capture and ionic discrimination of peptide and protein
      biomarkers with FraC nanopores.
AB  - Biological nanopores are nanoscale sensors employed for high-throughput, low
      cost, and long read-length DNA sequencing applications. The analysis and
      sequencing of proteins, however, is complicated by their folded structure and non
      uniform charge. Here we show that an electro-osmotic flow through Fragaceatoxin C
      (FraC) nanopores can be engineered to allow the entry of polypeptides at a fixed
      potential regardless of the charge composition of the polypeptide. We further use
      the nanopore currents to discriminate peptide and protein biomarkers from 25 kDa
      down to 1.3 kDa including polypeptides differing by one amino acid. On the road
      to nanopore proteomics, our findings represent a rationale for amino-acid
      analysis of folded and unfolded polypeptides with nanopores.Biological nanopore
      based protein sequencing and recognition is challenging due to the folded
      structure or non-uniform charge of peptides. Here the authors show that
      engineered FraC nanopores can overcome these problems and recognize biomarkers in
      the form of oligopeptides, polypeptides and folded proteins.

PMID- 29038541
TI  - NK cells are negatively regulated by sCD83 in experimental autoimmune uveitis.
AB  - Natural killer (NK) cells represent a subset of lymphocytes that contribute to
      innate immunity and have been reported to play a role in autoimmune uveitis.
      However, the mechanisms regulating NK cellular function in this condition remain
      unclear. Herein, we investigated the status of NK cells in experimental
      autoimmune uveitis (EAU). We found that the number of CD83+CD3-NK1.1+ cells was
      increased in the inflamed eyes and spleens of the EAU mouse model. At the
      recovery stage of EAU, serum concentrations of soluble CD83 (sCD83) were
      increased. sCD83 treatment relieved retinal tissue damage and decreased the
      number of infiltrating NK cells in inflamed eyes. Further analysis of the effects
      of sCD83 treatment in EAU revealed that it reduced: 1) the expressions of CD11b
      and CD83 in NK cells, 2) the percent of CD11bhighCD27lowCD3-NK1.1+ cells and 3)
      the secretion of granzyme B, perforin and IFN-gamma in NK cells as demonstrated
      both in vivo and in vitro. When sCD83 treated-NK cells were transferred into EAU
      mice, retinal tissue damage was relieved. These results demonstrate sCD83 down
      regulate NK cellular function and thus provide important, new information
      regarding the means for the beneficial effects of this agent in the treatment of
      autoimmune uveitis.

PMID- 29038540
TI  - Regulation of endothelial intracellular adenosine via adenosine kinase
      epigenetically modulates vascular inflammation.
AB  - The molecular mechanisms underlying vascular inflammation and associated
      inflammatory vascular diseases are not well defined. Here we show that
      endothelial intracellular adenosine and its key regulator adenosine kinase (ADK)
      play important roles in vascular inflammation. Pro-inflammatory stimuli lead to
      endothelial inflammation by increasing endothelial ADK expression, reducing the
      level of intracellular adenosine in endothelial cells, and activating the
      transmethylation pathway through increasing the association of ADK with S
      adenosylhomocysteine (SAH) hydrolase (SAHH). Increasing intracellular adenosine
      by genetic ADK knockdown or exogenous adenosine reduces activation of the
      transmethylation pathway and attenuates the endothelial inflammatory response. In
      addition, loss of endothelial ADK in mice leads to reduced atherosclerosis and
      affords protection against ischemia/reperfusion injury of the cerebral cortex.
      Taken together, these results demonstrate that intracellular adenosine, which is
      controlled by the key molecular regulator ADK, influences endothelial
      inflammation and vascular inflammatory diseases.The molecular mechanisms
      underlying vascular inflammation are unclear. Here the authors show that pro
      inflammatory stimuli lead to endothelial inflammation by increasing adenosine
      kinase expression, and that its knockdown in endothelial cells inhibits
      atherosclerosis and cerebral ischemic injury in mice.

PMID- 29038543
TI  - Advanced Silicon-on-Insulator: Crystalline Silicon on Atomic Layer Deposited
      Beryllium Oxide.
AB  - Silicon-on-insulator (SOI) technology improves the performance of devices by
      reducing parasitic capacitance. Devices based on SOI or silicon-on-sapphire
      technology are primarily used in high-performance radio frequency (RF) and
      radiation sensitive applications as well as for reducing the short channel
      effects in microelectronic devices. Despite their advantages, the high substrate
      cost and overheating problems associated with complexities in substrate
      fabrication as well as the low thermal conductivity of silicon oxide prevent
      broad applications of this technology. To overcome these challenges, we describe
      a new approach of using beryllium oxide (BeO). The use of atomic layer deposition
      (ALD) for producing this material results in lowering the SOI wafer production
      cost. Furthermore, the use of BeO exhibiting a high thermal conductivity might
      minimize the self-heating issues. We show that crystalline Si can be grown on ALD
      BeO and the resultant devices exhibit potential for use in advanced SOI
      technology applications.

PMID- 29038542
TI  - Store-operated Ca2+ Entry Facilitates the Lipopolysaccharide-induced
      Cyclooxygenase-2 Expression in Gastric Cancer Cells.
AB  - Helicobacter pylori has been identified as one of the major causes of chronic
      gastritis, gastric and duodenal ulcers, and gastric cancer. Lipopolysaccharide
      (LPS) is a major component of the outer membrane of gram-negative bacteria, and
      H. pylori LPS might play an exclusively important role in activating inflammatory
      pathways in monocytes and macrophages. To study the role of LPS in the underlying
      mechanism of inflammatory responses, we established an in vitro model using the
      human AGS gastric cancer cell line. We found that LPS mediates inflammation
      through setting off a cascade of events: activation of the store-operated calcium
      (SOC) channel, initiation of downstream NF-kappaB signaling, and phosphorylation
      of extracellular signal-regulated kinase 1/2 (ERK1/2). Phosphorylated ERK1/2
      promotes the nuclear translocation of NF-kappaB, and eventually elevates the
      expression level of COX-2, a major inflammatory gene.

PMID- 29038544
TI  - Amorphous lead oxide (a-PbO): suppression of signal lag via engineering of the
      layer structure.
AB  - Presence of a signal lag is a bottle neck of performance for many non-crystalline
      materials, considered for dynamic radiation sensing. Due to inadequate lag
      related temporal performance, polycrystalline layers of CdZnTe, PbI2, HgI2 and
      PbO are not practically utilized, despite their superior X-ray sensitivity and
      low production cost (even for large area detectors). In the current manuscript,
      we show that a technological step to replace nonhomogeneous disorder in
      polycrystalline PbO with homogeneous amorphous PbO structure suppresses signal
      lag and improves time response to X-ray irradiation. In addition, the newly
      developed amorphous lead oxide (a-PbO) possesses superior X-ray sensitivity in
      terms of electron-hole pair creation energy [Formula: see text] in comparison
      with amorphous selenium - currently the only photoconductor used as an X-ray-to
      charge transducer in the state-of-the-art direct conversion X-ray medical imaging
      systems. The proposed advances of the deposition process are low cost, easy to
      implement and with certain customization might potentially be applied to other
      materials, thus paving the way to their wide-range commercial use.

PMID- 29038545
TI  - Adjacent-possible ecological niche: growth of Lactobacillus species co-cultured
      with Escherichia coli in a synthetic minimal medium.
AB  - In certain conditions, members of the Lactobacillus genus are auxotrophs that
      have fastidious requirements for growth. Notably, Lactobacillus cannot grow in M9
      medium, a minimal synthetic medium used for Escherichia coli. However, we found
      that some Lactobacillus strains can be grown in M9 when co-cultured with E. coli
      K-12. In the co-culture, L. casei proliferates exponentially, reaching cell
      densities of 108 CFU (colony-forming unit) ml-1 in 6 h and dominating E. coli in
      the late growth phase. Spent medium from E. coli grown overnight lacked this
      growth-promoting effect on L. casei. Similarly, the effect was not observed when
      the species were separated by a 0.4-um membrane. Microscopic observations showed
      that L. casei are embedded in the micro-scale clusters of E. coli in the early
      growth phase. This study describes for the first time the ability of a
      Lactobacillus species to grow in minimal medium when in close proximity with co
      cultured bacteria.

PMID- 29038546
TI  - Oyster reproduction is compromised by acidification experienced seasonally in
      coastal regions.
AB  - Atmospheric carbon dioxide concentrations have been rising during the past
      century, leading to ocean acidification (OA). Coastal and estuarine habitats
      experience annual pH variability that vastly exceeds the magnitude of long-term
      projections in open ocean regions. Eastern oyster (Crassostrea virginica)
      reproduction season coincides with periods of low pH occurrence in estuaries,
      thus we investigated effects of moderate (pH 7.5, pCO2 2260 uatm) and severe OA
      (pH 7.1, pCO2 5584 uatm; and 6.7, pCO2 18480 uatm) on oyster gametogenesis,
      fertilization, and early larval development successes. Exposure at severe OA
      during gametogenesis caused disruption in oyster reproduction. Oogenesis appeared
      to be more sensitive compared to spermatogenesis. However, Eastern oyster
      reproduction was resilient to moderate OA projected for the near-future. In the
      context of projected climate change exacerbating seasonal acidification, OA of
      coastal habitats could represent a significant bottleneck for oyster reproduction
      which may have profound negative implications for coastal ecosystems reliant on
      this keystone species.

PMID- 29038547
TI  - A novel Fer/FerT targeting compound selectively evokes metabolic stress and
      necrotic death in malignant cells.
AB  - Disruption of the reprogrammed energy management system of malignant cells is a
      prioritized goal of targeted cancer therapy. Two regulators of this system are
      the Fer kinase, and its cancer cell specific variant, FerT, both residing in
      subcellular compartments including the mitochondrial electron transport chain.
      Here, we show that a newly developed inhibitor of Fer and FerT, E260, selectively
      evokes metabolic stress in cancer cells by imposing mitochondrial dysfunction and
      deformation, and onset of energy-consuming autophagy which decreases the cellular
      ATP level. Notably, Fer was also found to associate with PARP-1 and E260
      disrupted this association thereby leading to PARP-1 activation. The cooperative
      intervention with these metabolic pathways leads to energy crisis and necrotic
      death in malignant, but not in normal human cells, and to the suppression of
      tumors growth in vivo. Thus, E260 is a new anti-cancer agent which imposes
      metabolic stress and cellular death in cancer cells.The tyrosine-kinases Fer/FerT
      associate with the mitochondrial electron transport chain in cancer cells
      supporting their metabolic reprogramming. Here the authors discover a compound
      that disrupts Fer /FerT activity and selectively induces cell death of cancer
      cell lines displaying anti-tumor activity in vivo.

PMID- 29038548
TI  - Transmembrane Segment XI of the Na+/H+ Antiporter of S. pombe is a Critical Part
      of the Ion Translocation Pore.
AB  - The Na+/H+ exchanger of the plasma membrane of S. pombe (SpNHE1) removes
      intracellular sodium in exchange for an extracellular proton. We examined the
      structure and functional role of amino acids 360-393 of putative transmembrane
      (TM) segment XI of SpNHE1. Structural analysis suggested that it had a helical
      propensity over amino acids 360-368, an extended region from 369-378 and was
      helical over amino acids 379-386. TM XI was sensitive to side chain alterations.
      Mutation of eight amino acids to alanine resulted in loss of one or both of LiCl
      or NaCl tolerance when re-introduced into SpNHE1 deficient S. pombe. Mutation of
      seven other amino acids had minor effects. Analysis of structure and functional
      mutations suggested that Glu361 may be involved in cation coordination on the
      cytoplasmic face of the protein with a negative charge in this position being
      important. His367, Ile371 and Gly372 were important in function. Ile371 may have
      important hydrophobic interactions with other residues and Gly372 may be
      important in maintaining an extended conformation. Several residues from Val377
      to Leu384 are important in function possibly involved in hydrophobic interactions
      with other amino acids. We suggest that TM XI forms part of the ion translocation
      core of this Na+/H+ exchanger.

PMID- 29038549
TI  - Packing topology in crystals of proteins and small molecules: a comparison.
AB  - We compared the topologies of protein and small molecule crystals, which have
      many common features - both are molecular crystals with intermolecular
      interactions much weaker than intramolecular interactions. They also have
      different features - a considerably large fraction of the volume of protein
      crystals is occupied by liquid water while no room is available to other
      molecules in small molecule crystals. We analyzed the overall and local topology
      and performed multilevel topological analyses (with the software package
      ToposPro) of carefully selected high quality sets of protein and small molecule
      crystal structures. Given the suboptimal packing of protein crystals, which is
      due the special shape and size of proteins, it would be reasonable to expect that
      the topology of protein crystals is different from the topology of small molecule
      crystals. Surprisingly, we discovered that these two types of crystalline
      compounds have strikingly similar topologies. This might suggest that molecular
      crystal formations share symmetry rules independent of molecular dimension.

PMID- 29038550
TI  - Neural Network for Nanoscience Scanning Electron Microscope Image Recognition.
AB  - In this paper we applied transfer learning techniques for image recognition,
      automatic categorization, and labeling of nanoscience images obtained by scanning
      electron microscope (SEM). Roughly 20,000 SEM images were manually classified
      into 10 categories to form a labeled training set, which can be used as a
      reference set for future applications of deep learning enhanced algorithms in the
      nanoscience domain. The categories chosen spanned the range of 0-Dimensional (0D)
      objects such as particles, 1D nanowires and fibres, 2D films and coated surfaces,
      and 3D patterned surfaces such as pillars. The training set was used to retrain
      on the SEM dataset and to compare many convolutional neural network models
      (Inception-v3, Inception-v4, ResNet). We obtained compatible results by
      performing a feature extraction of the different models on the same dataset. We
      performed additional analysis of the classifier on a second test set to further
      investigate the results both on particular cases and from a statistical point of
      view. Our algorithm was able to successfully classify around 90% of a test
      dataset consisting of SEM images, while reduced accuracy was found in the case of
      images at the boundary between two categories or containing elements of multiple
      categories. In these cases, the image classification did not identify a
      predominant category with a high score. We used the statistical outcomes from
      testing to deploy a semi-automatic workflow able to classify and label images
      generated by the SEM. Finally, a separate training was performed to determine the
      volume fraction of coherently aligned nanowires in SEM images. The results were
      compared with what was obtained using the Local Gradient Orientation method. This
      example demonstrates the versatility and the potential of transfer learning to
      address specific tasks of interest in nanoscience applications.

PMID- 29038551
TI  - A novel machine learning approach reveals latent vascular phenotypes predictive
      of renal cancer outcome.
AB  - Gene expression signatures are commonly used as predictive biomarkers, but do not
      capture structural features within the tissue architecture. Here we apply a 2
      step machine learning framework for quantitative imaging of tumor vasculature to
      derive a spatially informed, prognostic gene signature. The trained algorithms
      classify endothelial cells and generate a vascular area mask (VAM) in H&E
      micrographs of clear cell renal cell carcinoma (ccRCC) cases from The Cancer
      Genome Atlas (TCGA). Quantification of VAMs led to the discovery of 9 vascular
      features (9VF) that predicted disease-free-survival in a discovery cohort (n =
      64, HR = 2.3). Correlation analysis and information gain identified a 14 gene
      expression signature related to the 9VF's. Two generalized linear models with
      elastic net regularization (14VF and 14GT), based on the 14 genes, separated
      independent cohorts of up to 301 cases into good and poor disease-free survival
      groups (14VF HR = 2.4, 14GT HR = 3.33). For the first time, we successfully
      applied digital image analysis and targeted machine learning to develop
      prognostic, morphology-based, gene expression signatures from the vascular
      architecture. This novel morphogenomic approach has the potential to improve
      previous methods for biomarker development.

PMID- 29038552
TI  - Regulating p-block metals in perovskite nanodots for efficient electrocatalytic
      water oxidation.
AB  - Water oxidation represents the core process of many sustainable energy systems,
      such as fuel cells, rechargeable metal-air batteries, and water splitting.
      Material surface defects with high-energy hanging bonds possess superb intrinsic
      reactivity, whose actual performance is limited by the dimension and conductivity
      of the electrocatalyst. Herein we propose a surface defect-rich perovskite
      electrocatalyst through a p-block metal regulation concept to achieve high
      performance for oxygen evolution. As a typical p-metal, Sn4+ dissolves from the
      solid phase from model SnNiFe perovskite nanodots, resulting in abundant surface
      defects with superior water oxidation performance. An oxygen pool model and a
      fusion-evolution mechanism are therefore proposed for the in-depth understanding
      of p-block metal regulation and the oxygen evolution reaction. The energy
      chemistry unveiled herein provides insights into water oxidation and helps to
      tackle critical issues in multi-electron oxygen electrocatalysis.Electrocatalysts
      that possess high densities of surface defects show great promise for efficient
      water oxidation. Here the authors demonstrate that regulating the p-block metal
      content in perovskite nanodots imparts these materials with abundant surface
      defects and excellent electrocatalytic activity.

PMID- 29038553
TI  - A comparison of passive and active estimates of sleep in a cohort with
      schizophrenia.
AB  - : Sleep abnormalities are considered an important feature of schizophrenia, yet
      convenient and reliable sleep monitoring remains a challenge. Smartphones offer a
      novel solution to capture both self-reported and objective measures of sleep in
      schizophrenia. In this three-month observational study, 17 subjects with a
      diagnosis of schizophrenia currently in treatment downloaded Beiwe, a platform
      for digital phenotyping, on their personal Apple or Android smartphones. Subjects
      were given tri-weekly ecological momentary assessments (EMAs) on their own
      smartphones, and passive data including accelerometer, GPS, screen use, and
      anonymized call and text message logs was continuously collected. We compare the
      in-clinic assessment of sleep quality, assessed with the Pittsburgh Sleep
      Questionnaire Inventory (PSQI), to EMAs, as well as sleep estimates based on
      passively collected accelerometer data. EMAs and passive data classified 85%
      (11/13) of subjects as exhibiting high or low sleep quality compared to the in
      clinic assessments among subjects who completed at least one in-person PSQI.
      Phone-based accelerometer data used to infer sleep duration was moderately
      correlated with subject self-assessment of sleep duration (r = 0.69, 95% CI 0.23
      0.90). Active and passive phone data predicts concurrent PSQI scores for all
      subjects with mean average error of 0.75 and future PSQI scores with a mean
      average error of 1.9, with scores ranging from 0-14. These results suggest sleep
      monitoring via personal smartphones is feasible for subjects with schizophrenia
      in a scalable and affordable manner. PATIENT MONITORING: SMARTPHONES CAN TRACK
      SCHIZOPHRENIA-RELATED SLEEP ABNORMALITIES: Smartphones may one-day offer
      accessible, clinically-useful insights into schizophrenia patients' sleep
      quality. Despite the clinical relevance of sleep to disease severity, monitoring
      technologies still evade convenience and reliability. In search of a preferential
      method, a group of Harvard University researchers led by Patrick Staples
      investigated the validity of data collected via patients' own mobile phones. The
      team, with a cohort of 17 schizophrenia patients, compared the quality of data
      produced by smartphone sensors and smartphone-delivered questionnaires to that of
      an in-clinic evaluation. The results significantly showed that smartphone
      monitoring could generate information that approached the accuracy of in-clinic
      assessments. The team noted some areas for improvement; however, this study
      provides convincing justifications for further research into this non-invasive,
      low-cost, scalable method to monitor the sleep quality of schizophrenic patients.

PMID- 29038554
TI  - Broadband dual-anisotropic solid metamaterials.
AB  - We have proposed solid elastic metamaterials with anisotropic stiffness and
      inertial mass simultaneously, denoted as the dual anisotropy, for the potential
      use of elastic wave controlling. The dual anisotropy has been designed weakly
      dispersive in a broad frequency range, wherein broadband anisotropic mass is
      achieved by employing the sliding-interface concept in fluid-solid composites.
      Results have been validated through the band-structure, effective-medium, and
      modal-field analyses. We have further found that the proposed solid metamaterial,
      when its shear stiffness is diminished until neglected, would reduce to the
      pentamode-inertial material model. This reduced model is the general form of
      mediums following transformation acoustic theory, which has been proved vital for
      acoustic wave controlling. Our studies are expected to pave a new route toward
      broadband acoustic and elastic wave controlling using dual-anisotropic solid
      metamaterials.

PMID- 29038555
TI  - Hybrid Printing Metal-mesh Transparent Conductive Films with Lower Energy
      Photonically Sintered Copper/tin Ink.
AB  - With the help of photonic sintering using intensive pulse light (IPL), copper has
      started to replace silver as a printable conductive material for printing
      electrodes in electronic circuits. However, to sinter copper ink, high energy IPL
      has to be used, which often causes electrode destruction, due to unreleased
      stress concentration and massive heat generated. In this study, a Cu/Sn hybrid
      ink has been developed by mixing Cu and Sn particles. The hybrid ink requires
      lower sintering energy than normal copper ink and has been successfully employed
      in a hybrid printing process to make metal-mesh transparent conductive films
      (TCFs). The sintering energy of Cu/Sn hybrid films with the mass ratio of 2:1 and
      1:1 (Cu:Sn) were decreased by 21% compared to sintering pure Cu film, which is
      attributed to the lower melting point of Sn for hybrid ink. Detailed study showed
      that the Sn particles were effectively fused among Cu particles and formed
      conducting path between them. The hybrid printed Cu/Sn metal-mesh TCF with line
      width of 3.5 MUm, high transmittance of 84% and low sheet resistance of 14
      Omega/? have been achieved with less defects and better quality than printed pure
      copper metal-mesh TCFs.

PMID- 29038556
TI  - Structural and Morphological Evolution for Water-resistant Organic
      Thermoelectrics.
AB  - We systematically investigated the effect of 2,5-bis(2-hydroxy-3
      methacryloyloxypropoxy)-1,4:3,6-dianhydro-sorbitol (Iso-GMA) with different
      concentrations on the structural and morphological evolution of poly(3,4
      ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) containing a fixed
      volume of dimethyl sulfoxide (DMSO) to realize water-resistant organic
      thermoelectric devices. As an additive, Iso-GMA is a hydrophilic and crosslinking
      agent that can interact with PEDOT and PSS chains by hydrogen bonding and/or
      dipole-dipole- or dipole-charge-interaction. The Seebeck coefficient and power
      factor in the film incorporating 3.0 vol% DMSO and 0.8 vol% Iso-GMA were
      respectively 1.82 * 102 and 1.53 * 105% higher than those of the pristine
      PEDOT:PSS film without additives (DMSO and Iso-GMA). These results can be
      attributed to the self-assembled and crosslinked fibril networks with optimized
      phase separation, where the film has densely-packed PEDOT and highly lamellar
      stacked PSS. Also, the reduced charge carrier concentration from the structural
      characteristics originated in the higher thermoelectric properties. We introduced
      the schematic illustration to understand the chemical bonding among the
      components and the morphological evolution according to the Iso-GMA
      concentration. The increased mechanical strength by the interchain stacking
      degree of PEDOT and the crosslinking of Iso-GMA facilitate the film remained in a
      water bath for 0.5 h without physical degradation, and sustain the thermoelectric
      properties during 12 h in humid conditons.

PMID- 29038557
TI  - Anti-Infective Effect of Adhesive Probiotic Lactobacillus in Fish is Correlated
      With Their Spatial Distribution in the Intestinal Tissue.
AB  - ABSTRACR: In this study, we tested the distribution of 49 Lactobacillus strains
      in the mucus and mucosa of the intestine tissue of zebrafish. We observed a
      progressive change in the spatial distribution of Lactobacillus strains, and
      suggested a division of the strains into three classes: mucus type (>70% in
      mucus), mucosa type (>70% in mucosa) and hybrid type (others). The hybrid type
      strains were more efficient in protection of zebrafish against Aeromonas
      hydrophila infection. Three strains representing different distribution types
      (JCM1149, CGMCC1.2028, and JCM 20300) were selected. The mucosa type strain
      JCM1149 induced higher intestinal expression of inflammatory cytokines and Hsp70
      than the other strains. Furthermore, we used L. rhamnosus GG and its mutant
      (PB22) lacking SpaCBA pili to investigate the influence of pili on spatial
      distribution. LGG showed a mucosa type distribution, while PB22 revealed a hybrid
      distribution and the disease protection was accordingly improved. The different
      protection ability between LGG and PB22 did not involve the intestinal
      microbiota, however, LGG induced injury to the mucosa of zebrafish. Collectively,
      the disease protection activity of Lactobacillus in zebrafish is correlated with
      their spatial distribution in the intestinal tissue, with strains showing a
      balanced distribution (hybrid type) more efficient in protection.

PMID- 29038558
TI  - Prokineticin receptor-1-dependent paracrine and autocrine pathways control
      cardiac tcf21+ fibroblast progenitor cell transformation into adipocytes and
      vascular cells.
AB  - Cardiac fat tissue volume and vascular dysfunction are strongly associated,
      accounting for overall body mass. Despite its pathophysiological significance,
      the origin and autocrine/paracrine pathways that regulate cardiac fat tissue and
      vascular network formation are unclear. We hypothesize that adipocytes and
      vasculogenic cells in adult mice hearts may share a common cardiac cells that
      could transform into adipocytes or vascular lineages, depending on the paracrine
      and autocrine stimuli. In this study utilizing transgenic mice overexpressing
      prokineticin receptor (PKR1) in cardiomyocytes, and tcf21ERT-creTM-derived
      cardiac fibroblast progenitor (CFP)-specific PKR1 knockout mice (PKR1 tcf-/-), as
      well as FACS-isolated CFPs, we showed that adipogenesis and vasculogenesis share
      a common CFPs originating from the tcf21+ epithelial lineage. We found that
      prokineticin-2 is a cardiomyocyte secretome that controls CFP transformation into
      adipocytes and vasculogenic cells in vivo and in vitro. Upon HFD exposure, PKR1
      tcf-/- mice displayed excessive fat deposition in the atrioventricular groove,
      perivascular area, and pericardium, which was accompanied by an impaired vascular
      network and cardiac dysfunction. This study contributes to the cardio-obesity
      field by demonstrating that PKR1 via autocrine/paracrine pathways controls CFP
      vasculogenic- and CFP-adipocyte-transformation in adult heart. Our study may open
      up new possibilities for the treatment of metabolic cardiac diseases and
      atherosclerosis.

PMID- 29038559
TI  - Large-scale transport of PM2.5 in the lower troposphere during winter cold surges
      in China.
AB  - A comprehensive investigation using the air quality network and meteorological
      data of China in 2015 showed that PM2.5 driven by cold surges from the ground
      level could travel up to 2000 km from northern to southern China within two days.
      Air pollution is more severe and prominent during the winter in north China due
      to seasonal variations in energy usage, trade wind movements, and industrial
      emissions. In February 2015, two cold surges traveling from north China caused a
      temporary increase in the concentration of PM2.5 in Shanghai. Subsequently, the
      concentration of PM2.5 in Xiamen increased to a high of 80 ug/m3, which is double
      the average PM2.5 concentration in Xiamen during the winter. This finding is a
      new long-range transport mechanism comparing to the well-established mechanism,
      with long-range transport more likely to occur in the upper troposphere than at
      lower levels. These observations were validated by results from the back
      trajectory analysis and the RAMS- CMAQ model. While wind speed was found to be a
      major facilitator in transporting PM2.5 from Beijing to Xiamen, more
      investigation is required to understand the complex relationship between wind
      speed and PM2.5 and how it moderates air quality in Beijing, Shanghai, and
      Xiamen.

PMID- 29038560
TI  - Safety assessment of antibiotic and probiotic feed additives for Gallus gallus
      domesticus.
AB  - Antibiotics in feed select for resistant strains and is thus a threat to human
      health. In this study, the effect of a multi-strain probiotic and antibiotics on
      the growth and health of broilers was studied. Equal numbers of broilers received
      on a daily basis either a multi-strain probiotic or a combination of
      sulphadiazine, colistin and trimethoprim, whereas the control group received
      standard feed. The villi of immature broilers (19 days old) administered
      antibiotics had a larger surface area and their lymphocyte and basophil counts
      were higher compared to broilers from the probiotic and control groups. The cecal
      microbiomes of mature broilers (29 days old) that received probiotics had higher
      levels of Enterobacteriaceae, but lower numbers of Clostridiales, Brucellaceae,
      Synergistaceae, Erysipelotrichaceae and Coriobacteriaceae compared to the
      antibiotic-treated group. A decline in the bioluminescence of Listeria
      monocytogenes observed for broilers on probiotics suggested that the probiotic
      may be used to control bacterial infections. No significant differences in total
      red blood cell, haemoglobin and haematocrit content, and mean values for
      corpuscular volume, corpuscular haemoglobin and corpuscular haemoglobin numbers
      were recorded amongst broilers from the different treatment groups. This study
      provides valuable information on the health and performance of broilers when
      administered probiotics and antibiotics as additives.

PMID- 29038562
TI  - Interacting Learning Processes during Skill Acquisition: Learning to control with
      gradually changing system dynamics.
AB  - There is increasing evidence that sensorimotor learning under real-life
      conditions relies on a composition of several learning processes. Nevertheless,
      most studies examine learning behaviour in relation to one specific learning
      mechanism. In this study, we examined the interaction between reward-based skill
      acquisition and motor adaptation to changes of object dynamics. Thirty healthy
      subjects, split into two groups, acquired the skill of balancing a pole on a cart
      in virtual reality. In one group, we gradually increased the gravity, making the
      task easier in the beginning and more difficult towards the end. In the second
      group, subjects had to acquire the skill on the maximum, most difficult gravity
      level. We hypothesized that the gradual increase in gravity during skill
      acquisition supports learning despite the necessary adjustments to changes in
      cart-pole dynamics. We found that the gradual group benefits from the slow
      increment, although overall improvement was interrupted by the changes in gravity
      and resulting system dynamics, which caused short-term degradations in
      performance and timing of actions. In conclusion, our results deliver evidence
      for an interaction of reward-based skill acquisition and motor adaptation
      processes, which indicates the importance of both processes for the development
      of optimized skill acquisition schedules.

PMID- 29038563
TI  - Use of pulmonary CT angiography with low tube voltage and low-iodine
      concentration contrast agent to diagnose pulmonary embolism.
AB  - Pulmonary CT angiography (CTPA) is regarded as the preferred imaging method in
      diagnosing pulmonary embolism (PE). Considering the harm of radiation exposure
      and the side effect of iodinated contrast agent, CTPA protocol with low tube
      voltage and low dose of contrast agent became research hotspot in last decade.
      The present study evaluates the image quality, radiation dose, positive rate of
      PE and the location of PE with a CTPA protocol using low tube voltage (80 kVp)
      and low-iodine-concentration contrast agent (270 mg I/ml) in patients suspected
      of PE compared to a conventional CTPA protocol (120 kVp, 350 mg I/ml). The
      results showed that 80 kVp CTPA protocol with 40 ml 270 mg I/ml achieved equally
      subjective image quality and a positive rate for diagnosing PE, though the
      quantitative image quality was reduced compared to the 120 kVp CTPA protocol with
      40 ml 350 mg I/ml administered, with a 63.6% decrease in radiation dose and a
      22.9% reduction in iodine content of contrast agent. Our results document that
      CTPA protocol with low tube voltage and low iodine concentration of contrast
      agent is satisfied to the clinical application.

PMID- 29038561
TI  - Vitamin D and cognitive function: A Mendelian randomisation study.
AB  - The causal nature of the association between hypovitaminosis D and poor cognitive
      function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR)
      approach, we examined the causal relationship between 25(OH)D and cognitive
      function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878),
      CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy
      25(OH)D. Cognitive tests were standardised into global and memory scores.
      Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta
      analyses assessed associations between 25(OH)D and cognitive function.
      Associations of serum 25(OH)D with global and memory-related cognitive function
      were non-linear (lower cognitive scores for both low and high 25(OH)D, p
      curvature <= 0.006), with much of the curvature attributed to a single study.
      DHCR7, CYP2R1, and the synthesis score were associated with small reductions in
      25(OH)D per vitamin D-decreasing allele. However, coefficients for associations
      with global or memory-related cognitive function were non-significant and in
      opposing directions for DHCR7 and CYP2R1, with no overall association observed
      for the synthesis score. Coefficients for the synthesis score and global and
      memory cognition were similar when stratified by 25(OH)D tertiles, sex and age.
      We found no evidence for serum 25(OH)D concentration as a causal factor for
      cognitive performance in mid- to later life.

PMID- 29038565
TI  - Prediction of high-pressure phases of Weyl semimetal NbAs and NbP.
AB  - As the first known Weyl semimetals, binary compounds including TaP, TaAs, NbAs,
      and NbP have received worldwide interest. This work explored the phase behaviours
      of NbAs and NbP under high pressure up to 200 GPa via first-principles
      calculations combined with intelligent particle swarm optimization. Upon
      compression, a new phase of NbAs with P-6m2 symmetry appeared above 23 GPa and
      remained stable until 38 GPa, whereupon a monoclinic structure with space group
      P2 1 /c became more energetically favourable. This lasted until 73 GPa, when a Pm
      3m phase followed. Surprisingly, NbP underwent a single phase transition around
      63.5 GPa to a new phase with Cmcm symmetry that was completely distinct from the
      structures shown by TaAs-class compounds such as NbAs and TaAs. All these newly
      pressure-stabilized structures were dynamically stable at both high and ambient
      pressure. Electronic band structure calculations revealed a transition from
      semimetal to metal under high pressure. This work is meaningful and fundamental
      for future studies and applications of TaAs-class Weyl semimetals under
      compression or extreme conditions.

PMID- 29038564
TI  - A quantitative comparison of cytosolic delivery via different protein uptake
      systems.
AB  - Over many years, a variety of delivery systems have been investigated that have
      the capacity to shuttle macromolecular cargoes, especially proteins, into the
      cytosol. Due to the lack of an objective way to quantify cytosolic delivery,
      relative delivery efficiencies of the various transport systems have remained
      unclear. Here, we demonstrate the use of the biotin ligase assay for a
      quantitative comparison of protein transport to the cytosol via cell-penetrating
      peptides, supercharged proteins and bacterial toxins in four different cell
      lines. The data illustrate large differences in both the total cellular
      internalization, which denotes any intracellular location including endosomes,
      and in the cytosolic uptake of the transport systems, with little correlation
      between the two. Also, we found significant differences between the cell lines.
      In general, protein transport systems based on cell-penetrating peptides show a
      modest total uptake, and mostly do not deliver cargo to the cytosol. Systems
      based on bacterial toxins show a modest receptor-mediated internalization but an
      efficient delivery to the cytosol. Supercharged proteins, on the contrary, are
      not receptor-specific and lead to massive total internalization into endosomes,
      but only low amounts end up in the cytosol.

PMID- 29038566
TI  - Structural variability and complexity of the giant Pithovirus sibericum particle
      revealed by high-voltage electron cryo-tomography and energy-filtered electron
      cryo-microscopy.
AB  - The Pithoviridae giant virus family exhibits the largest viral particle known so
      far, a prolate spheroid up to 2.5 MUm in length and 0.9 MUm in diameter. These
      particles show significant variations in size. Little is known about the
      structure of the intact virion due to technical limitations with conventional
      electron cryo-microscopy (cryo-EM) when imaging thick specimens. Here we present
      the intact structure of the giant Pithovirus sibericum particle at near native
      conditions using high-voltage electron cryo-tomography (cryo-ET) and energy
      filtered cryo-EM. We detected a previously undescribed low-density outer layer
      covering the tegument and a periodical structuring of the fibres in the striated
      apical cork. Energy-filtered Zernike phase-contrast cryo-EM images show distinct
      substructures inside the particles, implicating an internal compartmentalisation.
      The density of the interior volume of Pithovirus particles is three quarters
      lower than that of the Mimivirus. However, it is remarkably high given that the
      600 kbp Pithovirus genome is only half the size of the Mimivirus genome and is
      packaged in a volume up to 100 times larger. These observations suggest that the
      interior is densely packed with macromolecules in addition to the genomic nucleic
      acid.

PMID- 29038568
TI  - Impact of Coulomb Correlations on Magnetic Anisotropy in Mn3Ga Ferrimagnet.
AB  - Traditional density functional theory (DFT) miserably fails to reproduce the
      experimental volume and magnetic anisotropy of D022 Mn3Ga, which has recently
      become one of the most sought-after materials in order to achieve a stable spin
      switching at low current density. Despite great progress over the last 10 years,
      this issue has hitherto remained unsolved. Here, taking into account the effects
      of strong electronic correlations beyond what is included in standard DFT, we
      show by comparison with the experiment that the DFT+U method is capable of
      quantitatively describing the volume and the magnetic anisotropy energy (MAE) in
      this alloy with physically meaningful choice of onsite Coulomb-U parameter. For
      the first time using a plane-wave code, we decompose MAE into spin channel
      resolved components in order to determine spin-flip and spin-conserving
      contributions. The Mn atom at the tetrahedral site is identified as the primary
      source of the high perpendicular MAE with the most dominant spin-orbit coupling
      (SOC) occurring between its two orbital pairs: ?? coupling and ?? coupling
      between [Formula: see text] and d xy , and ?? coupling between d yz and [Formula:
      see text]. Using the SOC-perturbation theory model, we provide interpretation of
      our numerical results. These results are important for quantitative microscopic
      understanding of the large perpendicular MAE observed in this material, and
      should assist in harnessing its potential for applications in futuristic
      spintronic devices.

PMID- 29038567
TI  - Stabilization of mouse haploid embryonic stem cells with combined kinase and
      signal modulation.
AB  - Mammalian haploid embryonic stem cells (haESCs) provide new possibilities for
      large-scale genetic screens because they bear only one copy of each chromosome.
      However, haESCs are prone to spontaneous diploidization through unknown
      mechanisms. Here, we report that a small molecule combination could restrain
      mouse haESCs from diploidization by impeding exit from naive pluripotency and by
      shortening the S-G2/M phases. Combined with 2i and PD166285, our chemical
      cocktail could maintain haESCs in the haploid state for at least five weeks
      without fluorescence-activated cell sorting (FACS) enrichment of haploid cells.
      Taken together, we established an effective chemical approach for long-term
      maintenance of haESCs, and highlighted that proper cell cycle progression was
      critical for the maintenance of haploid state.

PMID- 29038569
TI  - The Incipient Motion Features of Sediment from Yangtze Estuary: Annular Flume
      Experiments.
AB  - In this study, annular flume experiments are carried out, using the sediment
      samples collected from Yangtze estuary. The incipient velocity and the incipient
      shear stress of three different groups of median grain size of sediment are
      given. The turbulent kinetic energy method (TKE) is used to determine the bed
      shear stress (tau), by evaluating variations in the suspended sediment
      concentration (SSC) within the water column. The suspended sediment concentration
      increases with the increase of the bed shear stress. When the sediment
      concentration reaches a certain concentration, the rate of change in tau
      obviously slows down. As the concentration increasing again, the bed shear stress
      grows rapidly with different growth rate attributed to different grain size. The
      results of the experiments indicate that SSC and grain size have strong influence
      on tau.

PMID- 29038570
TI  - Spin-polarised electrons in a one-magnet-only Mott spin junction.
AB  - The current flowing through a Mott spin junction depends on the relative spin
      orientation of the two ferromagnetic layers comprising the "source" and "drain"
      sides of the junction. The resulting current asymmetry is detected as giant or
      tunnelling magnetoresistance depending on whether the two ferromagnets are
      separated by a metal or an insulator. Based on the fundamental principles of
      reciprocity for spin-dependent electron scattering, one can envisage a one-magnet
      only spin junction in which the source is non-magnetic, and the spin information
      is encoded by the spin polarisation of the electrons that have crossed or are
      backscattered from the drain magnetic layer. The practical significance of using
      an unpolarised source is that the state of the magnetic layer can be modified
      without affecting the process of probing it. Whether this reciprocity is realised
      in the actual junctions is not yet known. Here, we demonstrate a nano-sized, one
      magnet-only Mott spin junction by measuring the finite spin polarisation of the
      backscattered electrons. Based on this finding, we conclude that since the
      junction acts as a spin filter, the magnetic layer must experience a spin
      transfer that could become detectable in view of the high current densities
      achievable in this technology.

PMID- 29038571
TI  - Highly sensitive and specific Alu-based quantification of human cells among
      rodent cells.
AB  - Alu elements are primate-specific short interspersed elements (SINEs), over 1
      million copies of which are present in the human genome; thus, Alu elements are
      useful targets for detecting human cells. However, previous Alu-based techniques
      for detecting human genomic DNA do not reach the theoretical limits of
      sensitivity and specificity. In this study, we developed a highly sensitive and
      specific Alu-based real-time PCR method for discriminating human cells from
      rodent cells, using a primer and probe set carefully designed to avoid possible
      cross-reactions with rodent genomes. From 100 ng of mixed human and rodent
      genomes, 1 fg of human genome, equivalent to 1 human cell in 100 million rodent
      cells, was detectable. Furthermore, in vivo mouse subrenal capsule
      xenotransplantation assays revealed that 10 human cells per mouse organ were
      detectable. In addition, after intravenous injection of human mesenchymal stem
      cells into NOD/SCID mice via tail vein, the biodistribution of human cells was
      trackable in the mouse lungs and kidneys for at least 1 week. Our findings
      indicate that our primer and probe set is applicable for the quantitative
      detection of tiny amounts of human cells, such as xenotransplanted human cancer
      or stem cells, in rodents.

PMID- 29038572
TI  - Higher-order Network Analysis of Fine Particulate Matter (PM 2.5) Transport in
      China at City Level.
AB  - Specification of PM 2.5 transmission characteristics is important for pollution
      control and policymaking. We apply higher-order organization of complex networks
      to identify major potential PM 2.5 contributors and PM 2.5 transport pathways of
      a network of 189 cities in China. The network we create in this paper consists of
      major cities in China and contains information on meteorological conditions of
      wind speed and wind direction, data on geographic distance, mountains, and PM 2.5
      concentrations. We aim to reveal PM 2.5 mobility between cities in China. Two
      major conclusions are revealed through motif analysis of complex networks. First,
      major potential PM 2.5 pollution contributors are identified for each cluster by
      one motif, which reflects movements from source to target. Second, transport
      pathways of PM 2.5 are revealed by another motif, which reflects transmission
      routes. To our knowledge, this is the first work to apply higher-order network
      analysis to study PM 2.5 transport.

PMID- 29038573
TI  - Significantly enhanced thermal conductivity of indium arsenide nanowires via
      sulfur passivation.
AB  - ABSTARCT: In this work, we experimentally investigated the effect of sulfur
      passivation on thermal transport in indium arsenide (InAs) nanowires. Our
      measurement results show that thermal conductivity can be enhanced by a ratio up
      to 159% by sulfur passivation. Current-voltage (I-V) measurements were performed
      on both unpassivated and S-passivated InAs nanowires to understand the mechanism
      of thermal conductivity enhancement. We observed a remarkable improvement in
      electrical conductivity upon sulfur passivation and a significant contribution of
      electrons to thermal conductivity, which account for the enhanced thermal
      conductivity of the S-passivated InAs nanowires.

PMID- 29038574
TI  - Annual community patterns are driven by seasonal switching between closely
      related marine bacteria.
AB  - This corrects the article DOI: 10.1038/ismej.2017.4.

PMID- 29038575
TI  - Human rickettsial pathogen modulates arthropod organic anion transporting
      polypeptide and tryptophan pathway for its survival in ticks.
AB  - The black-legged tick Ixodes scapularis transmits the human anaplasmosis agent,
      Anaplasma phagocytophilum. In this study, we show that A. phagocytophilum
      specifically up-regulates I. scapularis organic anion transporting polypeptide,
      isoatp4056 and kynurenine amino transferase (kat), a gene involved in the
      production of tryptophan metabolite xanthurenic acid (XA), for its survival in
      ticks. RNAi analysis revealed that knockdown of isoatp4056 expression had no
      effect on A. phagocytophilum acquisition from the murine host but affected the
      bacterial survival in tick cells. Knockdown of the expression of kat mRNA alone
      or in combination with isoatp4056 mRNA significantly affected A. phagocytophilum
      survival and isoatp4056 expression in tick cells. Exogenous addition of XA
      induces isoatp4056 expression and A. phagocytophilum burden in both tick salivary
      glands and tick cells. Electrophoretic mobility shift assays provide further
      evidence that A. phagocytophilum and XA influences isoatp4056 expression.
      Collectively, this study provides important novel information in understanding
      the interplay between molecular pathways manipulated by a rickettsial pathogen to
      survive in its arthropod vector.

PMID- 29038576
TI  - Size effect on the deformation mechanisms of nanocrystalline platinum thin films.
AB  - This paper reports a study of time-resolved deformation process at the atomic
      scale of a nanocrystalline Pt thin film captured in situ under a transmission
      electron microscope. The main mechanism of plastic deformation was found to
      evolve from full dislocation activity-enabled plasticity in large grains (with
      grain size d > 10 nm), to partial dislocation plasticity in smaller grains (with
      grain size 10 nm < d < 6 nm), and grain boundary-mediated plasticity in the
      matrix with grain sizes d < 6 nm. The critical grain size for the transition from
      full dislocation activity to partial dislocation activity was estimated based on
      consideration of stacking fault energy. For grain boundary-mediated plasticity,
      the possible contributions to strain rate of grain creep, grain sliding and grain
      rotation to plastic deformation were estimated using established models. The
      contribution of grain creep is found to be negligible, the contribution of grain
      rotation is effective but limited in magnitude, and grain sliding is suggested to
      be the dominant deformation mechanism in nanocrystalline Pt thin films. This
      study provided the direct evidence of these deformation processes at the atomic
      scale.

PMID- 29038577
TI  - Morphology engineering of Streptomyces coelicolor M145 by sub-inhibitory
      concentrations of antibiotics.
AB  - Growth of Streptomyces in submerged culture is characterized by the formation of
      complex mycelial particles, known as pellets or clumps, which strongly influence
      antibiotic production. Also, many bioactive molecules produced by Streptomyces
      have great potential to modulate soil bacteria morphological development.
      However, there has been no effort directed at engineering mycelial morphology
      using these small molecules. Here, thiostrepton was identified, using a
      combination of qRT-PCR, semi-preparative HPLC, and MALDI-TOF MS, as a pellet
      inducing compound produced by S. laurentii ATCC31255. At sub-inhibitory
      concentration, thiostrepton stimulated Streptomyces coelicolor M145 pellet
      formation and antibiotics production were altered, with 3-fold and 2-fold
      decreases in actinorhodin and undecylprodigiosin yields, respectively. It was
      also shown that mycelial morphology can be influenced by other antibiotic class
      at sub-inhibitory concentrations. For instance, in the presence of spectinomycin,
      S. coelicolor M145, which under typical growth conditions forms large diameter
      pellets with many protruding hyphae, instead formed small diameter pellets with
      barely visible hyphae at the edge. Importantly, this morphology produced a 4-fold
      increase in undecylprodigiosin production and 3-fold decrease in actinorhodin
      production. These results indicated that these small molecules, previously
      identified as antimicrobials, also have great potential for influencing mycelial
      morphology.

PMID- 29038578
TI  - Conversion of FeCo from soft to hard magnetic material by lattice engineering and
      nanopatterning.
AB  - The development of magnetic materials with large uniaxial magnetic anisotropy (K
      u) and high saturation magnetization has attracted much attention in various
      areas such as high-density magnetic storage, spintronic devices, and permanent
      magnets. Although FeCo alloys with the body-centred cubic structure exhibit the
      highest M s among all transition metal alloys, their low K u and coercivity (H c)
      make them unsuitable for these applications. However, recent first-principles
      calculations have predicted large K u for the FeCo films with the body-centred
      tetragonal structure. In this work, we experimentally investigated the hard
      magnetic properties and magnetic domain structures of nanopatterned FeCo alloy
      thin films. As a result, a relatively large value of the perpendicular uniaxial
      magnetic anisotropy K u = 2.1 * 106 J.m-3 was obtained, while the H c of the
      nanopatterned FeCo layers increased with decreasing dot pattern size. The maximum
      H c measured in this study was 4.8 * 105 A.m-1, and the corresponding value of MU
      0 H c was 0.60 T, where MU 0 represented the vacuum permeability.

PMID- 29038579
TI  - Synthesis of single-phase L10-FeNi magnet powder by nitrogen insertion and
      topotactic extraction.
AB  - Tetrataenite (L10-FeNi) is a promising candidate for use as a permanent magnet
      free of rare-earth elements because of its favorable properties. In this study,
      single-phase L10-FeNi powder with a high degree of order was synthesized through
      a new method, nitrogen insertion and topotactic extraction (NITE). In the method,
      FeNiN, which has the same ordered arrangement as L10-FeNi, is formed by nitriding
      A1-FeNi powder with ammonia gas. Subsequently, FeNiN is denitrided by topotactic
      reaction to derive single-phase L10-FeNi with an order parameter of 0.71. The
      transformation of disordered-phase FeNi into the L10 phase increased the coercive
      force from 14.5 kA/m to 142 kA/m. The proposed method not only significantly
      accelerates the development of magnets using L10-FeNi but also offers a new
      synthesis route to obtain ordered alloys in non-equilibrium states.

PMID- 29038580
TI  - A novel library of -arylketones as potential inhibitors of alpha-glucosidase:
      Their design, synthesis, in vitro and in vivo studies.
AB  - alpha-glucosidase is an essential enzyme located at the brush border of
      intestines. It is an important therapeutic target for type II diabetes. Herein we
      have designed a library of novel alpha-arylketones as inhibitors of alpha
      glucosidase (yeast origin) via scaffold hopping and bioisosteric modification of
      known inhibitors of alpha-glucosidase. The design was validated through molecular
      docking that revealed strong binding interactions of the newly designed compounds
      against alpha-glucosidase. A library comprising of 15 compounds was synthesized
      in a combinatorial fashion, where the advanced amide intermediates were accessed
      through "shot gun" synthesis. The final compounds were characterized by 1H, 13C
      NMR and with high resolution mass spectroscopy. In vitro screening of the
      compounds against yeast alpha-glucosidase revealed substantial inhibition with
      IC50s in the range of 4-10 MUM (the standard drug acarbose inhibits alpha
      glucosidase with an IC50 of 9.95 MUM). Reaction kinetics suggested mixed type
      inhibition. Finally, in vivo studies of the most active compound 3c against
      Streptozotocin induced male albino Wistar rats revealed that its administration
      in the rats for about 4 weeks lead to a highly significant (P < 0.001) decrease
      in the fasting blood glucose (FBG) compared to the untreated diabetic rats.
      Moreover, lower dose of 3c had better control over FBG in contrast to high-dose.

PMID- 29038581
TI  - Transcriptional repression of Plxnc1 by Lmx1a and Lmx1b directs topographic
      dopaminergic circuit formation.
AB  - Mesodiencephalic dopamine neurons play central roles in the regulation of a wide
      range of brain functions, including voluntary movement and behavioral processes.
      These functions are served by distinct subtypes of mesodiencephalic dopamine
      neurons located in the substantia nigra pars compacta and the ventral tegmental
      area, which form the nigrostriatal, mesolimbic, and mesocortical pathways. Until
      now, mechanisms involved in dopaminergic circuit formation remained largely
      unknown. Here, we show that Lmx1a, Lmx1b, and Otx2 transcription factors control
      subtype-specific mesodiencephalic dopamine neurons and their appropriate axon
      innervation. Our results revealed that the expression of Plxnc1, an axon guidance
      receptor, is repressed by Lmx1a/b and enhanced by Otx2. We also found that
      Sema7a/Plxnc1 interactions are responsible for the segregation of nigrostriatal
      and mesolimbic dopaminergic pathways. These findings identify Lmx1a/b, Otx2, and
      Plxnc1 as determinants of dopaminergic circuit formation and should assist in
      engineering mesodiencephalic dopamine neurons capable of regenerating appropriate
      connections for cell therapy.Midbrain dopaminergic neurons (mDAs) in the VTA and
      SNpc project to different regions and form distinct circuits. Here the authors
      show that transcription factors Lmx1a, Lmx1b, and Otx2 control the axon guidance
      of mDAs and the segregation of mesolimbic and nigrostriatal dopaminergic
      pathways.

PMID- 29038582
TI  - Direct visualization of critical hydrogen atoms in a pyridoxal 5'-phosphate
      enzyme.
AB  - Enzymes dependent on pyridoxal 5'-phosphate (PLP, the active form of vitamin B6)
      perform a myriad of diverse chemical transformations. They promote various
      reactions by modulating the electronic states of PLP through weak interactions in
      the active site. Neutron crystallography has the unique ability of visualizing
      the nuclear positions of hydrogen atoms in macromolecules. Here we present a room
      temperature neutron structure of a homodimeric PLP-dependent enzyme, aspartate
      aminotransferase, which was reacted in situ with alpha-methylaspartate. In one
      monomer, the PLP remained as an internal aldimine with a deprotonated Schiff
      base. In the second monomer, the external aldimine formed with the substrate
      analog. We observe a deuterium equidistant between the Schiff base and the C
      terminal carboxylate of the substrate, a position indicative of a low-barrier
      hydrogen bond. Quantum chemical calculations and a low-pH room-temperature X-ray
      structure provide insight into the physical phenomena that control the electronic
      modulation in aspartate aminotransferase.Pyridoxal 5'-phosphate (PLP) is a
      ubiquitous co factor for diverse enzymes, among them aspartate aminotransferase.
      Here the authors use neutron crystallography, which allows the visualization of
      the positions of hydrogen atoms, and computation to characterize the catalytic
      mechanism of the enzyme.

PMID- 29038583
TI  - Zdhhc13-dependent Drp1 S-palmitoylation impacts brain bioenergetics, anxiety,
      coordination and motor skills.
AB  - Protein S-palmitoylation is a reversible post-translational modification mediated
      by palmitoyl acyltransferase enzymes, a group of Zn2+-finger DHHC-domain
      containing proteins (ZDHHC). Here, for the first time, we show that Zdhhc13 plays
      a key role in anxiety-related behaviors and motor function, as well as brain
      bioenergetics, in a mouse model (luc) carrying a spontaneous Zdhhc13 recessive
      mutation. At 3 m of age, mutant mice displayed increased sensorimotor gating,
      anxiety, hypoactivity, and decreased motor coordination, compared to littermate
      controls. Loss of Zdhhc13 in cortex and cerebellum from 3- and 24 m old hetero-
      and homozygous male mutant mice resulted in lower levels of Drp1 S-palmitoylation
      accompanied by altered mitochondrial dynamics, increased glycolysis,
      glutaminolysis and lactic acidosis, and neurotransmitter imbalances. Employing in
      vivo and in vitro models, we identified that Zdhhc13-dependent Drp1 S
      palmitoylation, which acting alone or in concert, enables the normal occurrence
      of the fission-fusion process. In vitro and in vivo direct Zdhhc13-Drp1 protein
      interaction was observed, confirming Drp1 as a substrate of Zdhhc13. Abnormal
      fission-fusion processes result in disrupted mitochondria morphology and
      distribution affecting not only mitochondrial ATP output but neurotransmission
      and integrity of synaptic structures in the brain, setting the basis for the
      behavioral abnormalities described in the Zdhhc13-deficient mice.

PMID- 29038584
TI  - Dual-Drug Containing Core-Shell Nanoparticles for Lung Cancer Therapy.
AB  - Late-stage diagnosis of lung cancer occurs ~95% of the time due to late
      manifestation of its symptoms, necessitating rigorous treatment following
      diagnosis. Existing treatment methods are limited by lack of specificity,
      systemic toxicity, temporary remission, and radio-resistance in lung cancer
      cells. In this research, we have developed a folate receptor-targeting
      multifunctional dual drug-loaded nanoparticle (MDNP) containing a poly(N
      isopropylacrylamide)-carboxymethyl chitosan shell and poly lactic-co-glycolic
      acid (PLGA) core for enhancing localized chemo-radiotherapy to effectively treat
      lung cancers. The formulation provided controlled releases of the encapsulated
      therapeutic compounds, NU7441 - a potent radiosensitizer, and gemcitabine - an
      FDA approved chemotherapeutic drug for lung cancer chemo-radiotherapy. The MDNPs
      showed biphasic NU7441 release and pH-dependent release of gemcitabine. These
      nanoparticles also demonstrated good stability, excellent hemocompatibility,
      outstanding in vitro cytocompatibility with alveolar Type I cells, and dose
      dependent caveolae-mediated in vitro uptake by lung cancer cells. In addition,
      they could be encapsulated with superparamagnetic iron oxide (SPIO) nanoparticles
      and visualized by MRI in vivo. Preliminary in vivo results demonstrated the low
      toxicity of these particles and their use in chemo-radiotherapy to effectively
      reduce lung tumors. These results indicate that MDNPs can potentially be used as
      nano-vehicles to provide simultaneous chemotherapy and radiation sensitization
      for lung cancer treatment.

PMID- 29038585
TI  - Tissue and plasma levels of galectins in patients with high grade serous ovarian
      carcinoma as new predictive biomarkers.
AB  - Galectins are moving closer to center stage in detecting glycosylation aberration
      in cancer cells. Here, we have investigated the expression of galectins in
      ovarian cancer (OC) and examined their potential as biomarkers in tissues and
      blood plasma samples of high grade serous ovarian carcinoma (HGSC) patients. In
      tissues, we found that increased protein expression of stromal gal-1 and
      epithelial gal-8/9 was associated with a poor response to treatment of HGSC
      patients. Gal-8/9 were both independent predictors of chemoresistance and overall
      survival (OS), respectively. This galectin signature increased the predictive
      value of the cancer antigen 125 (CA125) on 5-year disease-free survival (DFS),
      post-chemotherapy treatment and 5-year OS. In CA125LOW patients, epithelial gal-9
      was associated with a lower 5-year OS while stromal gal-1 and epithelial gal-8
      were both associated with a lower 5-year DFS. Such negative predictive value of
      gal-8 and gal-9 was also found using plasma samples. In both cases, high plasma
      levels of gal-8 and gal-9 was associated with a lower OS and DFS. Overall, these
      data suggest that galectins may be promising biomarkers to identify subgroups of
      HGSC patients with poorer prognosis. Our study also contributes to better define
      the heterogeneity of the disease.

PMID- 29038586
TI  - Invariant nature of substituted element in metal-hexacyanoferrate.
AB  - The chemical substitution of a transition metal (M) is an effective method to
      improve the functionality of materials. In order to design the highly functional
      materials, we first have to know the local structure and electronic state around
      the substituted element. Here, we systematically investigated the local structure
      and electronic state of the host (M h) and guest (M g) transition metals in metal
      hexacyanoferrate (M-HCF), Na x (M h, M g)[Fe(CN)6] y (1.40 < x < 1.60 and 0.85 <
      y < 0.90), by means of extended X-ray absorption fine structure (EXAFS) and X-ray
      absorption near-edge structure (XANES) analyses. The EXAFS and XANES analyses
      revealed that the local structure and electronic state around M g are essentially
      the same as those in the pure compound, i.e, M g-HCF. Such an invariant nature of
      M g in M-HCF is in sharp contrast with that in layered oxide, in which the M g
      valence changes so that local M g-O distance (d M-Og) approaches the M h-O
      distance (d M-Oh).

PMID- 29038588
TI  - Patterns and underlying mechanisms of non-volant small mammal richness along two
      contrasting mountain slopes in southwestern China.
AB  - The species richness patterns of small mammals and the processes shaping them in
      two gradients of a mountain with different spatial and climatic characteristics
      were examined using standard sampling scheme. We trapped 2,006 small mammals
      representing 37 species, along elevational gradients on both western and eastern
      slopes of the Ailao Mountains, Southwest China. Using mid-domain effect model,
      model selection and model averaging, we examined the effects of slope, area, mean
      annual temperature (MAT), mean annual humidity (MAH), productivity, plant species
      richness (PSR) and the mid-domain effect (MDE) on the patterns of small mammal
      diversity. The hump-shaped patterns were favored along the elevational gradient,
      but shapes of diversity curves were different on the contrasting slopes. Area and
      productivity were the most important factors in explaining the variation of total
      species richness. However, for each specific group of small mammals (i.e.
      insectivores vs. rodents, large-ranged vs. small-ranged species, endemic vs. non
      endemic species), the peaks of species richness and their primary drivers varied.
      The major explanatory factors for richness pattern of each small mammal group
      were not significantly different between the slopes, suggesting the existence of
      the general underlying mechanisms on two slopes of a mountain.

PMID- 29038587
TI  - Cell-surface major vault protein promotes cancer progression through harboring
      mesenchymal and intermediate circulating tumor cells in hepatocellular
      carcinomas.
AB  - Circulating tumor cells (CTCs) play a major role in the metastasis and recurrence
      of hepatocellular carcinoma (HCC). Here, we found that major vault protein (MVP)
      is expressed on the surface of HCC cells and further induced under stressful
      environments. MVP knockdown reduces cell proliferation and induces apoptosis in
      HCC cells. Treatment of HCC cells with anti-MVP antibody (alpha-MVP) recognizing
      cell-surface MVP (csMVP) inhibits cell proliferation, migration, and invasion.
      csMVP-positive HCC cells have a higher clonogenic survival than csMVP-negative
      HCC cells, and treatment of HCC cells with alpha-MVP inhibits clonogenic
      survival, suggesting that csMVP contributes to HCC cell survival, migration, and
      invasion. The function of csMVP is mediated through mTOR, FAK, ERK and Akt
      signaling pathways. csMVP-positive CTCs are detected in HCC patients (89.7%) but
      not in healthy donors, and the number of csMVP-positive CTCs is further increased
      in patients with metastatic cancers. csMVP is exclusively detectable in CTCs with
      mesenchymal phenotype or intermediate phenotype with neither epithelial nor
      mesenchymal markers, suggesting that csMVP-associated survival and metastatic
      potential harbor CTCs with nonepithelial phenotypes. The results suggest that
      csMVP promotes cancer progression and serves as a surface marker for mesenchymal
      and intermediate CTCs in patients with HCC and metastatic cancers.

PMID- 29038589
TI  - Estimation of the age of human bloodstains under the simulated indoor and outdoor
      crime scene conditions by ATR-FTIR spectroscopy.
AB  - Estimation of the age of human bloodstains is of great importance in forensic
      practices, but it is a challenging task because of the lack of a well-accepted,
      reliable, and established method. Here, the attenuated total reflection (ATR)
      Fourier transform infrared (FTIR) technique combined with advanced chemometric
      methods was utilized to determine the age of indoor and outdoor bloodstains up to
      107 days. The bloodstain storage conditions mimicked crime scene scenarios as
      closely as possible. Two partial least squares regression models-indoor and
      outdoor models with 7-85 days-exhibited good performance for external validation,
      with low values of predictive root mean squared error (5.83 and 4.77) and high R2
      values (0.94 and 0.96) and residual predictive deviation (4.08 and 5.14),
      respectively. Two partial least squares-discriminant analysis classification
      models were built and demonstrated excellent distinction between fresh (age <=1
      d) and older (age >1 d) bloodstains, which is highly valuable for forensic
      investigations. These findings demonstrate that ATR-FTIR spectroscopy coupled
      with advanced chemometric methods can be employed as a rapid and non-destructive
      tool for age estimation of bloodstains in real-world forensic investigation.

PMID- 29038590
TI  - Chronic hepatitis C liver microenvironment: role of the Th17/Treg interplay
      related to fibrogenesis.
AB  - The role of the different lymphocyte populations in liver microenvironment of
      chronic hepatitis C (CHC) patients is still matter of debate. Since Th17 and Treg
      have opposite functions, their balance could affect disease progression. The aim
      was to explore liver microenvironment and its peripheral blood counterpart in
      adult CHC patients. CD4+ lymphocytes were predominant in the liver, with high
      Foxp3+ but low IL-17A+ frequency. IL-17A+ lymphocytes and IL-17A+/Foxp3+ ratio
      displayed association with advanced fibrosis (p = 0.0130; p = 0.0236,
      respectively), while Foxp3+ lymphocytes and IL-10 expression level inversely
      correlated with fibrosis severity (p = 0.0381, p = 0.0398, respectively). TGF
      beta/IL-6 ratio correlated with IL-17A+/Foxp3+ ratio (p = 0.0036, r = 0.5944) and
      with IL-17A+ lymphocytes (p = 0.0093; r = 0.5203). TNF-alpha and TGF-beta were
      associated with hepatitis severity (p = 0.0409, p = 0.0321). Peripheral blood
      lymphocyte frequency was not associated with liver damage. There are functionally
      different immune cell populations actively involved in liver damage, but the
      liver cytokine milieu actually drives the pathogenesis. The intrahepatic Foxp3+
      lymphocytes predominance beside the low IL-17A+ lymphocytes frequency, delineate
      a skewed IL-17A+/Foxp3+ balance towards Foxp3+ lymphocytes. However, the IL-17A+
      lymphocytes association with advanced fibrosis denotes their role in the
      pathogenesis. Therefore, the interplay between Th17 and Treg conditions liver
      fibrogenesis.

PMID- 29038591
TI  - Genomics alterations of metastatic and primary tissues across 15 cancer types.
AB  - Metastasis is an important event for cancer evolution and prognosis. In this
      article, we analyzed the differences in genomic alterations between primary and
      metastatic tissues at hotspot regions in 15 cancer types and 10,456 samples.
      Differential somatic mutations at the amino acid, protein domain and gene levels,
      mutational exclusiveness, and copy number variations were identified in these
      cancers, while no significant nucleotide and gene fusion differences were
      detected. The homogeneity and heterogeneity of these differences in cancers were
      also detected. By characterizing the genomic alterations of these genes,
      important signaling pathways during metastasis were also identified. In summary,
      the metastatic cancer tissues retained most genomic features of the primary tumor
      at the biological level and acquired new signatures during cancer cell migration.

PMID- 29038592
TI  - In vivo imaging of lung inflammation with neutrophil-specific 68Ga nano
      radiotracer.
AB  - In vivo detection and quantification of inflammation is a major goal in molecular
      imaging. Furthermore, cell-specific detection of inflammation would be a
      tremendous advantage in the characterization of many diseases. Here, we show how
      this goal can be achieved through the synergistic combination of nanotechnology
      and nuclear imaging. One of the most remarkable features of this hybrid approach
      is the possibility to tailor the pharmacokinetics of the nanomaterial
      incorporated biomolecule and radionuclide. A good example of this approach is the
      covalent binding of a large amount of a neutrophil-specific, hydrophobic peptide
      on the surface of 68Ga core-doped nanoparticles. This new nano-radiotracer has
      been used for non-invasive in vivo detection of acute inflammation with very high
      in vivo labelling efficiency, i.e. a large percentage of labelled neutrophils.
      Furthermore, we demonstrate that the tracer is neutrophil-specific and yields
      images of neutrophil recruitment of unprecedented quality. Finally, the nano
      radiotracer was successfully detected in chronic inflammation in atherosclerosis
      prone ApoE-/- mice after several weeks on a high-fat diet.

PMID- 29038593
TI  - Gender-and lesion number-dependent difference in "atherogenic index of plasma" in
      Chinese people with coronary heart disease.
AB  - Few studies has investigated the interrelationship between Atherogenic index of
      plasma (AIP) and coronary heart disease (CHD) especially in Asians. AIP is the
      logarithmically transformed ratio of triglyceride (TG) to high-density
      lipoprotein cholesterol (HDL-C), and is thought to be associated with
      arteriosclerosis, hypertension, diabetes and cardiovascular diseases. Of the 463
      patients from Central Hospital of Nanchong in 2011-2014 diagnosed with
      angiograms, 229 CHD (>50% stenosis in one or more arteries) and the rest 234 were
      the controls (maximum stenosis < 10% in any artery) according to the world health
      organization (who) diagnostic criteria. The multiple regression analysis showed
      that AIP was independently associated with CHD in men (odds ratio (OR) = 4.44,
      95%CI 1.62-12.21, P = 0.004) after adjusting for age, body mass index (BMI),
      fasting blood glucose(FBG), homocysteine (Hcy), and smoking, but not in women (OR
      = 0.47, 95%CI 0.11-2.08, P = 0.318). Subgroup analysis showed that the
      significant difference in AIP between the CHD and the controls only exists in
      patients with multi-vessel lesions but not in those with single-vessel lesion.
      Further large-scale studies with balanced sex ratio and vessel lesion numbers
      should verify the present findings.

PMID- 29038594
TI  - Synthetic nanocomposite MgH2/5 wt. % TiMn2 powders for solid-hydrogen storage
      tank integrated with PEM fuel cell.
AB  - Storing hydrogen gas into cylinders under high pressure of 350 bar is not safe
      and still needs many intensive studies dedic ated for tank's manufacturing.
      Liquid hydrogen faces also severe practical difficulties due to its very low
      density, leading to larger fuel tanks three times larger than traditional
      gasoline tank. Moreover, converting hydrogen gas into liquid phase is not an
      economic process since it consumes high energy needed to cool down the gas
      temperature to -252.8  degrees C. One practical solution is storing hydrogen gas
      in metal lattice such as Mg powder and its nanocomposites in the form of MgH2.
      There are two major issues should be solved first. One related to MgH2 in which
      its inherent poor hydrogenation/dehydrogenation kinetics and high thermal
      stability must be improved. Secondly, related to providing a safe tank. Here we
      have succeeded to prepare a new binary system of MgH2/5 wt. % TiMn2 nanocomposite
      powder that show excellent hydrogenation/dehydrogenation behavior at relatively
      low temperature (250  degrees C) with long cycle-life-time (1400 h). Moreover, a
      simple hydrogen storage tank filled with our synthetic nanocomposite powders was
      designed and tested in electrical charging a battery of a cell phone device at
      180  degrees C through a commercial fuel cell.

PMID- 29038595
TI  - Covariate selection for association screening in multiphenotype genetic studies.
AB  - Testing for associations in big data faces the problem of multiple comparisons,
      wherein true signals are difficult to detect on the background of all
      associations queried. This difficulty is particularly salient in human genetic
      association studies, in which phenotypic variation is often driven by numerous
      variants of small effect. The current strategy to improve power to identify these
      weak associations consists of applying standard marginal statistical approaches
      and increasing study sample sizes. Although successful, this approach does not
      leverage the environmental and genetic factors shared among the multiple
      phenotypes collected in contemporary cohorts. Here we developed covariates for
      multiphenotype studies (CMS), an approach that improves power when correlated
      phenotypes are measured on the same samples. Our analyses of real and simulated
      data provide direct evidence that correlated phenotypes can be used to achieve
      increases in power to levels often surpassing the power gained by a twofold
      increase in sample size.

PMID- 29038596
TI  - A quantitative genetic framework highlights the role of epistatic effects for
      grain-yield heterosis in bread wheat.
AB  - Increasing wheat yield is a key global challenge to producing sufficient food for
      a growing human population. Wheat grain yield can be boosted by exploiting
      heterosis, the superior performance of hybrids compared with midparents. Here we
      present a tailored quantitative genetic framework to study the genetic basis of
      midparent heterosis in hybrid populations derived from crosses among diverse
      parents. We applied this framework to an extensive data set assembled for winter
      wheat. Grain yield was assessed for 1,604 hybrids and their 135 parental elite
      breeding lines in 11 environments. The hybrids outperformed the midparents by 10%
      on average, representing approximately 15 years of breeding progress in wheat,
      thus further substantiating the remarkable potential of hybrid-wheat breeding.
      Genome-wide prediction and association mapping implemented through the developed
      quantitative genetic framework showed that dominance effects played a less
      prominent role than epistatic effects in grain-yield heterosis in wheat.

PMID- 29038597
TI  - Simultaneous visualisation of calcified bone microstructure and intracortical
      vasculature using synchrotron X-ray phase contrast-enhanced tomography.
AB  - 3D imaging of the bone vasculature is of key importance in the understanding of
      skeletal disease. As blood vessels in bone are deeply encased in the calcified
      matrix, imaging techniques that are applicable to soft tissues are generally
      difficult or impossible to apply to the skeleton. While canals in cortical bone
      can readily be identified and characterised in X-ray computed tomographic data in
      3D, the soft tissue comprising blood vessels that are putatively contained within
      the canal structures does not provide sufficient image contrast necessary for
      image segmentation. Here, we report an approach that allows for rapid,
      simultaneous visualisation of calcified bone tissue and the vasculature within
      the calcified bone matrix. Using synchrotron X-ray phase contrast-enhanced
      tomography we show exemplar data with intracortical capillaries uncovered at sub
      micrometre level without the need for any staining or contrast agent. Using the
      tibiofibular junction of 15 week-old C57BL/6 mice post mortem, we show the bone
      cortical porosity simultaneously along with the soft tissue comprising the
      vasculature. Validation with histology confirms that we can resolve individual
      capillaries. This imaging approach could be easily applied to other skeletal
      sites and transgenic models, and could improve our understanding of the role the
      vasculature plays in bone disease.

PMID- 29038598
TI  - Male-specific deficits in natural reward learning in a mouse model of
      neurodevelopmental disorders.
AB  - Neurodevelopmental disorders, including autism spectrum disorders, are highly
      male biased, but the underpinnings of this are unknown. Striatal dysfunction has
      been strongly implicated in the pathophysiology of neurodevelopmental disorders,
      raising the question of whether there are sex differences in how the striatum is
      impacted by genetic risk factors linked to neurodevelopmental disorders. Here we
      report male-specific deficits in striatal function important to reward learning
      in a mouse model of 16p11.2 hemideletion, a genetic mutation that is strongly
      associated with the risk of neurodevelopmental disorders, particularly autism and
      attention-deficit hyperactivity disorder. We find that male, but not female,
      16p11.2 deletion animals show impairments in reward-directed learning and
      maintaining motivation to work for rewards. Male, but not female, deletion
      animals overexpress mRNA for dopamine receptor 2 and adenosine receptor 2a in the
      striatum, markers of medium spiny neurons signaling via the indirect pathway,
      associated with behavioral inhibition. Both sexes show a 50% reduction of mRNA
      levels of the genes located within the 16p11.2 region in the striatum, including
      the kinase extracellular-signal related kinase 1 (ERK1). However, hemideletion
      males show increased activation in the striatum for ERK1, both at baseline and in
      response to sucrose, a signaling change associated with decreased striatal
      plasticity. This increase in ERK1 phosphorylation is coupled with a decrease in
      the abundance of the ERK phosphatase striatum-enriched protein-tyrosine
      phosphatase in hemideletion males. In contrast, females do not show activation of
      ERK1 in response to sucrose, but notably hemideletion females show elevated
      protein levels for ERK1 as well as the related kinase ERK2 over what would be
      predicted by mRNA levels. These data indicate profound sex differences in the
      impact of a genetic lesion linked with neurodevelopmental disorders, including
      mechanisms of male-specific vulnerability and female-specific resilience
      impacting intracellular signaling in the brain.

PMID- 29038600
TI  - Novel evidence for paternal dietary influences on cognitive and neural functions
      in offspring mice.

PMID- 29038601
TI  - A structural model of flagellar filament switching across multiple bacterial
      species.
AB  - The bacterial flagellar filament has long been studied to understand how a
      polymer composed of a single protein can switch between different supercoiled
      states with high cooperativity. Here we present near-atomic resolution cryo-EM
      structures for flagellar filaments from both Gram-positive Bacillus subtilis and
      Gram-negative Pseudomonas aeruginosa. Seven mutant flagellar filaments in B.
      subtilis and two in P. aeruginosa capture two different states of the filament.
      These reliable atomic models of both states reveal conserved molecular
      interactions in the interior of the filament among B. subtilis, P. aeruginosa and
      Salmonella enterica. Using the detailed information about the molecular
      interactions in two filament states, we successfully predict point mutations that
      shift the equilibrium between those two states. Further, we observe the
      dimerization of P. aeruginosa outer domains without any perturbation of the
      conserved interior of the filament. Our results give new insights into how the
      flagellin sequence has been "tuned" over evolution.Bacterial flagellar filaments
      are composed almost entirely of a single protein-flagellin-which can switch
      between different supercoiled states in a highly cooperative manner. Here the
      authors present near-atomic resolution cryo-EM structures of nine flagellar
      filaments, and begin to shed light on the molecular basis of filament switching.

PMID- 29038603
TI  - Experimental verification of the rotational type of chiral spin spiral structures
      by spin-polarized scanning tunneling microscopy.
AB  - We report on experimental verification of the rotational type of chiral spin
      spirals in Mn thin films on a W(110) substrate using spin-polarized scanning
      tunneling microscopy (SP-STM) with a double-axis superconducting vector magnet.
      From SP-STM images using Fe-coated W tips magnetized to the out-of-plane and
      [001] directions, we found that both Mn mono- and double-layers exhibit cycloidal
      rotation whose spins rotate in the planes normal to the propagating directions.
      Our results agree with the theoretical prediction based on the symmetry of the
      system, supporting that the magnetic structures are driven by the interfacial
      Dzyaloshinskii-Moriya interaction.

PMID- 29038602
TI  - Blood pressure and cholesterol level checks as dynamic interrelated screening
      examinations.
AB  - This study analysed the determinants of screening uptake for blood pressure and
      cholesterol level checks. Furthermore, it investigated the presence of possible
      spillover effects from one type of cardiovascular screening to another type of
      cardiovascular screening. A dynamic random effects bivariate panel probit model
      with initial conditions (Wooldridge-type estimator) was adopted for the
      estimation. The outcome variables were the participation in blood pressure and
      cholesterol level checks by individuals in a given year. The balanced panel
      sample of 21,138 observations was constructed from 1,626 individuals from the
      British Household Panel Survey (BHPS) between 1996 and 2008. The analysis showed
      the significance of past screening behaviour for both cardiovascular screening
      examinations. For both cardiovascular screening examinations state dependence
      exist. The study also shows a significant spillover effect of the cholesterol
      level check on the blood pressure check and vice versa. Also a poorer health
      status led to a higher uptake for both types of screening examinations. Changes
      in recommendations have to consider the fact that taking part in one type of
      cardiovascular screening examination can influence the decision to take part in
      the other type of cardiovascular screening examination.

PMID- 29038604
TI  - Overexpression of OSM and IL-6 impacts the polarization of pro-fibrotic
      macrophages and the development of bleomycin-induced lung fibrosis.
AB  - Although recent evidence indicates that gp130 cytokines, Oncostatin M (OSM) and
      IL-6 are involved in alternative programming of macrophages, their role in lung
      fibrogenesis is poorly understood. Here, we investigated the effect of transient
      adenoviral overexpression of OSM or IL-6 in mice during bleomycin-induced lung
      fibrosis. Lung fibrosis and M2-like macrophage accumulation were assessed by
      immunohistochemistry, western blotting, gene expression and flow cytometry. Ex
      vivo isolated alveolar and bone marrow-derived macrophages were examined for M2
      like programming and signalling. Airway physiology measurements at day 21
      demonstrated that overexpression of OSM or IL-6 exacerbated bleomycin-induced
      lung elastance, consistent with histopathological assessment of extracellular
      matrix and myofibroblast accumulation. Flow cytometry analysis at day 7 showed
      increased numbers of M2-like macrophages in lungs of mice exposed to bleomycin
      and OSM or IL-6. These macrophages expressed the IL-6Ralpha, but were deficient
      for OSMRbeta, suggesting that IL-6, but not OSM, may directly induce alternative
      macrophage activation. In conclusion, the gp130 cytokines IL-6 and OSM contribute
      to the accumulation of profibrotic macrophages and enhancement of bleomycin
      induced lung fibrosis. This study suggests that therapeutic strategies targeting
      these cytokines or their receptors may be beneficial to prevent the accumulation
      of M2-like macrophages and the progression of fibrotic lung disease.

PMID- 29038605
TI  - Enantiomeric excess by magnetic circular dichroism in Archaean atmosphere.
AB  - Evolution of homochirality requires an initial enantiomeric excess (EE) between
      right and left-handed biomolecules. We show that magnetic circular dichroism
      (MCD) of sun's ultraviolet C light by oxygen in Archaean earth's anoxic
      atmosphere followed by chirally selective damage of biomolecules due to circular
      dichroism (CD) can generate EE of correct handedness. Our calculation of EE uses
      published data for CD of biomolecules and accepted magnitude for Archaean earth's
      magnetic field. Independent of atmospheric oxygen concentration calculated EE has
      the same sign for all pyrimidine nucleosides which is opposite to that for amino
      acids. Purine nucleosides have smaller EE values with opposite sign to
      pyrimidines but are less susceptible to UV damage. Homochirality is explained by
      origin of prebiotic life in one hemisphere of earth and its evolution to EE ~ +/-
      1 before reversal of terrestrial magnetic field. Chirality of biomolecules is
      decided by the direction of magnetic field where prebiotic life originated on
      Archaean earth.

PMID- 29038606
TI  - Joint Estimation of Multiple Dependent Gaussian Graphical Models with
      Applications to Mouse Genomics.
AB  - Gaussian graphical models are widely used to represent conditional dependence
      among random variables. In this paper, we propose a novel estimator for data
      arising from a group of Gaussian graphical models that are themselves dependent.
      A motivating example is that of modeling gene expression collected on multiple
      tissues from the same individual: here the multivariate outcome is affected by
      dependencies acting not only at the level of the specific tissues, but also at
      the level of the whole body; existing methods that assume independence among
      graphs are not applicable in this case. To estimate multiple dependent graphs, we
      decompose the problem into two graphical layers: the systemic layer, which
      affects all outcomes and thereby induces cross-graph dependence, and the category
      specific layer, which represents graph-specific variation. We propose a graphical
      EM technique that estimates both layers jointly, establish estimation consistency
      and selection sparsistency of the proposed estimator, and confirm by simulation
      that the EM method is superior to a simple one-step method. We apply our
      technique to mouse genomics data and obtain biologically plausible results.

PMID- 29038599
TI  - Widespread white matter microstructural differences in schizophrenia across 4322
      individuals: results from the ENIGMA Schizophrenia DTI Working Group.
AB  - The regional distribution of white matter (WM) abnormalities in schizophrenia
      remains poorly understood, and reported disease effects on the brain vary widely
      between studies. In an effort to identify commonalities across studies, we
      perform what we believe is the first ever large-scale coordinated study of WM
      microstructural differences in schizophrenia. Our analysis consisted of 2359
      healthy controls and 1963 schizophrenia patients from 29 independent
      international studies; we harmonized the processing and statistical analyses of
      diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across
      studies. Significant reductions in fractional anisotropy (FA) in schizophrenia
      patients were widespread, and detected in 20 of 25 regions of interest within a
      WM skeleton representing all major WM fasciculi. Effect sizes varied by region,
      peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas
      as opposed to the core WM where regions of interest were defined. The anterior
      corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body
      (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to
      lesser degrees, were observed in almost all regions analyzed. Larger effect sizes
      were observed for FA than diffusivity measures; significantly higher mean and
      radial diffusivity was observed for schizophrenia patients compared with
      controls. No significant effects of age at onset of schizophrenia or medication
      dosage were detected. As the largest coordinated analysis of WM differences in a
      psychiatric disorder to date, the present study provides a robust profile of
      widespread WM abnormalities in schizophrenia patients worldwide. Interactive
      three-dimensional visualization of the results is available at www.enigma
      viewer.org.

PMID- 29038607
TI  - Advanced, Analytic, Automated (AAA) Measurement of Engagement During Learning.
AB  - It is generally acknowledged that engagement plays a critical role in learning.
      Unfortunately, the study of engagement has been stymied by a lack of valid and
      efficient measures. We introduce the advanced, analytic, and automated (AAA)
      approach to measure engagement at fine-grained temporal resolutions. The AAA
      measurement approach is grounded in embodied theories of cognition and affect,
      which advocate a close coupling between thought and action. It uses machine
      learned computational models to automatically infer mental states associated with
      engagement (e.g., interest, flow) from machine-readable behavioral and
      physiological signals (e.g., facial expressions, eye tracking, click-stream data)
      and from aspects of the environmental context. We present15 case studies that
      illustrate the potential of the AAA approach for measuring engagement in digital
      learning environments. We discuss strengths and weaknesses of the AAA approach,
      concluding that it has significant promise to catalyze engagement research.

PMID- 29038608
TI  - Cali, Colombia, Key learning City C/Can 2025: City Cancer Challenge.

PMID- 29038609
TI  - Lies, Damned Lies, and Survey Self-Reports? Identity as a Cause of Measurement
      Bias.
AB  - Explanations of error in survey self-reports have focused on social desirability:
      that respondents answer questions about normative behavior to appear prosocial to
      interviewers. However, this paradigm fails to explain why bias occurs even in
      self-administered modes like mail and web surveys. We offer an alternative
      explanation rooted in identity theory that focuses on measurement directiveness
      as a cause of bias. After completing questions about physical exercise on a web
      survey, respondents completed a text message-based reporting procedure, sending
      updates on their major activities for five days. Random assignment was then made
      to one of two conditions: instructions mentioned the focus of the study, physical
      exercise, or not. Survey responses, text updates, and records from recreation
      facilities were compared. Direct measures generated bias-overreporting in survey
      measures and reactivity in the directive text condition-but the nondirective text
      condition generated unbiased measures. Findings are discussed in terms of
      identity.

PMID- 29038610
TI  - Unique and interactive effects of impulsivity facets on reckless driving and
      driving under the influence in a high-risk young adult sample.
AB  - Risky driving behaviors are disproportionately high among young adults and
      impulsivity is a robust risk factor. Recent conceptualizations have proposed
      multidimensional facets of impulsivity comprised of negative urgency,
      premeditation, perseverance, sensation seeking, and positive urgency (UPPS-P
      model). Prior studies have found these facets are associated with risky driving
      behaviors in college student samples, but no prior studies have examined these
      facets in clinical samples. This study examined the unique and interactive
      effects of UPPS-P impulsivity facets on past-year risky driving behaviors in a
      sample of high-risk young adults (ages 18-30 years) with a history of substance
      use and antisocial behavior and their siblings (n=1,100). Multilevel Poisson
      regressions indicated that sensation seeking and negative urgency were uniquely
      and positively associated with both frequency of past-year reckless driving and
      driving under the influence. Moreover, lack of premeditation was uniquely and
      positively associated with reckless driving, whereas lack of perseverance was
      uniquely and positively associated with driving under the influence. Furthermore,
      lack of premeditation moderated and strengthened the positive association between
      sensation seeking and driving under the influence. These study findings suggest
      that assessing multiple facets of trait impulsivity could facilitate targeted
      prevention efforts among young adults with a history of externalizing
      psychopathology.

PMID- 29038611
TI  - Paying Research Participants: The Outsized Influence of "Undue Influence".

PMID- 29038612
TI  - DNA Methylation as a Noninvasive Epigenetic Biomarker for the Detection of
      Cancer.
AB  - In light of the high incidence and mortality rates of cancer, early and accurate
      diagnosis is an important priority for assigning optimal treatment for each
      individual with suspected illness. Biomarkers are crucial in the screening of
      patients with a high risk of developing cancer, diagnosing patients with
      suspicious tumours at the earliest possible stage, establishing an accurate
      prognosis, and predicting and monitoring the response to specific therapies.
      Epigenetic alterations are innovative biomarkers for cancer, due to their
      stability, frequency, and noninvasive accessibility in bodily fluids. Epigenetic
      modifications are also reversible and potentially useful as therapeutic targets.
      Despite this, there is still a lack of accurate biomarkers for the conclusive
      diagnosis of most cancer types; thus, there is a strong need for continued
      investigation to expand this area of research. In this review, we summarise
      current knowledge on methylated DNA and its implications in cancer to explore its
      potential as an epigenetic biomarker to be translated for clinical application.
      We propose that the identification of biomarkers with higher accuracy and more
      effective detection methods will enable improved clinical management of patients
      and the intervention at early-stage disease.

PMID- 29038613
TI  - Nasal Cytology as a Marker of Atopy in Children.
AB  - The aim of this study was to evaluate the cytological picture of nasal mucosa in
      children with atopic diseases and to determine the diagnostic value of the test
      for the diagnosis of atopic diseases. The study included 140 children from 4
      months to 17 years old. Among children with a history of atopy, there were 30
      children with atopic dermatitis, 30 children with asthma, and 46 children with
      allergic rhinitis. The control group consisted of 34 healthy children. The nasal
      scraping technique has been used to collect samples from the nasal cavity. The
      samples were evaluated under light microscope. Epithelial cells as well as
      infiltrating cells were assessed. The only statistically significant group of
      cells differentiating children with atopic disease and without atopy were
      eosinophils, which in children with atopy were significantly more common.
      Assuming a significant eosinophilia value of at least 5% of all cells in
      cytogram, the sensitivity of nasal cytology in allergic rhinitis was 52.2%, in
      asthma 33.3%, and in atopic dermatitis 13.3%. The specificity of the test in
      atopic diseases was 94.1%. It can be concluded that nasal cytology with
      eosinophilia assessment can be a useful tool for an early diagnosis of atopic
      disease in children.

PMID- 29038614
TI  - DNA Methylation Events as Markers for Diagnosis and Management of Acute Myeloid
      Leukemia and Myelodysplastic Syndrome.
AB  - During the onset and progression of hematological malignancies, many changes
      occur in cellular epigenome, such as hypo- or hypermethylation of CpG islands in
      promoter regions. DNA methylation is an epigenetic modification that regulates
      gene expression and is a key event for tumorigenesis. The continuous search for
      biomarkers that signal early disease, indicate prognosis, and act as therapeutic
      targets has led to studies investigating the role of DNA in cancer onset and
      progression. This review focuses on DNA methylation changes as potential
      biomarkers for diagnosis, prognosis, response to treatment, and early toxicity in
      acute myeloid leukemia and myelodysplastic syndrome. Here, we report that
      distinct changes in DNA methylation may alter gene function and drive malignant
      cellular transformation during several stages of leukemogenesis. Most of these
      modifications occur at an early stage of disease and may predict myeloid/lymphoid
      transformation or response to therapy, which justifies its use as a biomarker for
      disease onset and progression. Methylation patterns, or its dynamic change during
      treatment, may also be used as markers for patient stratification, disease
      prognosis, and response to treatment. Further investigations of methylation
      modifications as therapeutic biomarkers, which may correlate with therapeutic
      response and/or predict treatment toxicity, are still warranted.

PMID- 29038616
TI  - SUMO E3 Ligase PIASy Mediates High Glucose-Induced Activation of NF-kappaB
      Inflammatory Signaling in Rat Mesangial Cells.
AB  - BACKGROUND: Sumoylation is extensively involved in the regulation of NF-kappaB
      signaling. PIASy, as a SUMO E3 ligase, has been proved to mediate sumoylation of
      IkappaB kinase gamma (IKKgamma) and contribute to the activation of NF-kappaB
      under genotoxic agent stimulation. However, the association of PIASy and NF
      kappaB signaling in the pathogenesis of diabetic nephropathy (DN) has not been
      defined. METHODS: Rat glomerular mesangial cells (GMCs) were stimulated by high
      glucose; siRNA was constructed to silence the expression of PIASy; the expression
      of PIASy, SUMO isoforms (SUMO1, SUMO2/3), and NF-kappaB signaling components was
      analyzed by Western blot; the interaction between IKKgamma and SUMO proteins was
      detected by coimmunoprecipitation; and the release of inflammatory cytokines MCP
      1 and IL-6 was assayed by ELISA. RESULTS: High glucose significantly upregulated
      the expression of PIASy, SUMO1, and SUMO2/3 in a dose- and time-dependent manner
      (P < 0.05), induced the phosphorylation and sumoylation of IKKgamma (P < 0.05),
      and then triggered NF-kappaB signaling whereas MCP-1 and IL-6 were released from
      GMCs (P < 0.05). Moreover, these high glucose-induced effects were observably
      reversed by siRNA-mediated knockdown of PIASy (P < 0.05). CONCLUSION: The SUMO E3
      ligase PIASy mediates high glucose-induced activation of NF-kappaB inflammatory
      signaling, suggesting that PIASy may be a potential therapeutic target of DN.

PMID- 29038615
TI  - Red Blood Cell Distribution Width: A Novel Predictive Indicator for
      Cardiovascular and Cerebrovascular Diseases.
AB  - The red blood cell distribution width (RDW) obtained from a standard complete
      blood count (CBC) is a convenient and inexpensive biochemical parameter
      representing the variability in size of circulating erythrocytes. Over the past
      few decades, RDW with mean corpuscular volume (MCV) has been used to identify
      quite a few hematological system diseases including iron-deficiency anemia and
      bone marrow dysfunction. In recent years, many clinical studies have proved that
      the alterations of RDW levels may be associated with the incidence and prognosis
      in many cardiovascular and cerebrovascular diseases (CVDs). Therefore, early
      detection and intervention in time of these vascular diseases is critical for
      delaying their progression. RDW as a new predictive marker and an independent
      risk factor plays a significant role in assessing the severity and progression of
      CVDs. However, the mechanisms of the association between RDW and the prognosis of
      CVDs remain unclear. In this review, we will provide an overview of the
      representative literatures concerning hypothetical and potential epidemiological
      associations between RDW and CVDs and discuss the underlying mechanisms.

PMID- 29038617
TI  - Patients with Systemic Lupus Erythematosus Show Increased Levels and Defective
      Function of CD69+ T Regulatory Cells.
AB  - T regulatory (Treg) cells have a key role in the pathogenesis of chronic
      inflammatory and autoimmune diseases. A CD4+CD69+ T cell subset has been
      described that behaves as Treg lymphocytes, exerting an important immune
      suppressive effect. In this study, we analyzed the levels and function of
      CD4+CD69+ Treg cells in patients with systemic lupus erythematosus (SLE). Blood
      samples were obtained from 22 patients with SLE and 25 healthy subjects. Levels
      of CD4+CD69+ Treg cells were analyzed by multiparametric flow cytometry, and
      their function was measured by an assay of suppression of lymphocyte activation
      and through the inhibition of cytokine synthesis. We found an increased percent
      of CD4+CD25varCD69+TGF-beta+IL-10+Foxp3- lymphocytes in patients with SLE
      compared to controls. In addition, a significant diminution in the suppressive
      effect of these cells on the activation of autologous T lymphocytes was observed
      in most patients with SLE. Accordingly, CD69+ Treg cells from SLE patients showed
      a defective capability to inhibit the release of IL-2, IL-6, IL-10, and IL-17A by
      autologous lymphocytes. Our findings suggest that while CD4+CD69+ Treg lymphocyte
      levels are increased in SLE patients, these cells are apparently unable to
      contribute to the downmodulation of the autoimmune response and the tissue damage
      seen in this condition.

PMID- 29038618
TI  - Mediators of Inflammation and Angiogenesis in Chronic Spontaneous Urticaria: Are
      They Potential Biomarkers of the Disease?
AB  - In chronic spontaneous urticaria (CSU), different pathophysiological mechanisms,
      potentially responsible for the development of the disease, have been recently
      described. It is likely that the activation of skin mast cells with consequent
      release of histamine and other proinflammatory mediators is responsible for
      vasodilation in the lesional skin of CSU. However, the underlying causes of mast
      cell activation in the disease are largely unknown and remain to be identified.
      Thus, in this review, we discuss new insights in the pathogenesis of CSU,
      focusing on inflammation and angiogenesis. The understanding of these mechanisms
      will enable the identification of biomarkers useful for the diagnosis, follow-up,
      and management of CSU and will allow the development of novel, more specific, and
      patient-tailored therapies.

PMID- 29038619
TI  - Alteration of Inflammatory Mediators in the Upper and Lower Airways under Chronic
      Intermittent Hypoxia: Preliminary Animal Study.
AB  - PURPOSE: We hypothesized that CIH may affect the upper airway immune system and
      aimed to verify whether CIH can induce airway inflammation in a murine
      obstructive sleep apnea (OSA) model. METHODS: C57BL6 male mice were exposed to
      intermittent hypoxia (CIH group; 5 ~ 21% FiO2, 120 sec cycles, 12 h/d, n = 6) or
      room air (Sham group, n = 6) for up to 4 weeks in identical chambers. Nasal and
      lung tissues and lavage fluid were collected and analyzed by multiplex assay.
      Lung lavage fluid was also utilized for FACS analysis to determine eosinophil
      count. RESULTS: We determined the protein level of 24 different cytokines,
      chemokines, and inflammatory mediators. Among various cytokines, levels of IL
      1alpha, IL-1beta, IL-4, IL-6, and IL-13 were significantly elevated in nose or
      lung tissue from the CIH group. In addition, MCP-1 and periostin were elevated in
      nose and lung tissue and lavage fluid from the CIH group. CONCLUSIONS: CIH for 4
      weeks altered the levels of inflammatory mediators in both the nose and lungs of
      mouse model. We suggest that the airway immune system may be deteriorated by CIH
      and allergic inflammation in the upper or lower airway could be worsened by sleep
      apnea.

PMID- 29038620
TI  - Dengue Virus Induces NK Cell Activation through TRAIL Expression during
      Infection.
AB  - Dengue is an acute febrile illness with a wide spectrum of signs and symptoms
      ranging from mild to severe forms characterized by plasma leakage that can be
      fatal. NK cells are one of the main effectors in early infection and may play an
      important role in dengue pathogenesis. We investigated NK cell involvement during
      dengue infection. A higher frequency of NK cell subsets and TRAIL+NK cells was
      found in mild DF cases when compared to that in severe cases or healthy donors.
      NK activation markers such as CD107a and TLR3 were upregulated in patients' cells
      compared to those in healthy donors. In addition, IL12 related to NK cell
      activation were upregulated in mild DF cases. In vitro PBMC culture models show
      that DENV-stimulated and IFNalpha-stimulated NK cells were able to express TRAIL,
      suggesting an indirect activation of cells, regarding TRAIL expression. Type I
      IFN receptor blockage on DENV-stimulated PBMCs showed TRAIL expression on NK
      cells is partially IFNalpha dependent. In addition, during PBMC stimulation,
      TRAIL expression on NK cells was inversely correlated with DENV-positive
      monocytes. Therefore, we observed DENV-induced activation of NK cell populations.
      A higher activation of NK cells would promote limited viral spread, resulting in
      decreased inflammatory response, contributing to protection against dengue
      severity.

PMID- 29038621
TI  - TWEAK/Fn14 Activation Participates in Skin Inflammation.
AB  - Tumor necrosis factor- (TNF-) like weak inducer of apoptosis (TWEAK) participates
      in multiple biological activities via binding to its sole receptor-fibroblast
      growth factor-inducible 14 (Fn14). The TWEAK/Fn14 signaling pathway is activated
      in skin inflammation and modulates the inflammatory responses of keratinocytes by
      activating nuclear factor-kappaB signals and enhancing the production of several
      cytokines, including interleukins, monocyte chemotactic protein-1, RANTES
      (regulated on activation, normal T cell expressed and secreted), and interferon
      gamma-induced protein 10. Mild or transient TWEAK/Fn14 activation contributes to
      tissular repair and regeneration while excessive or persistent TWEAK/Fn14 signals
      may lead to severe inflammatory infiltration and tissue damage. TWEAK also
      regulates cell fate of keratinocytes, involving the function of Fn14-TNF receptor
      associated factor-TNF receptor axis. By recruiting inflammatory cells, promoting
      cytokine production, and regulating cell fate, TWEAK/Fn14 activation plays a
      pivotal role in the pathogenesis of various skin disorders, such as psoriasis,
      atopic dermatitis, cutaneous vasculitis, human papillomavirus infection and
      related skin tumors, and cutaneous autoimmune diseases. Therefore, the TWEAK/Fn14
      pathway may be a potential target for the development of novel therapeutics for
      skin inflammatory diseases.

PMID- 29038624
TI  - Comparing the Efficiency of Two Different Extraction Techniques in Removal of
      Maxillary Third Molars: A Randomized Controlled Trial.
AB  - INTRODUCTION: Extractions are routine procedures in dental surgery. Traditional
      extraction techniques use a combination of severing the periodontal attachment,
      luxation with an elevator, and removal with forceps. A new technique of
      extraction of maxillary third molar is introduced in this study-Joedds technique,
      which is compared with the conventional technique. METHODS AND MATERIAL: One
      hundred people were included in the study, the people were divided into two
      groups by means of simple random sampling. In one group conventional technique of
      maxillary third molar extraction was used and on second Joedds technique was
      used. Statistical analysis was carried out with student's t test. RESULTS:
      Analysis of 100 patients based on parameters showed that the novel joedds
      technique had minimal trauma to surrounding tissues, less tuberosity and root
      fractures and the time taken for extraction was <2 min while compared to other
      group of patients. CONCLUSION: This novel technique has proved to be better than
      conventional third molar extraction technique, with minimal complications. If
      Proper selection of cases and right technique are used.

PMID- 29038622
TI  - Inflexibility as a Vulnerability to Depression: A Systematic Qualitative Review.
AB  - The study of vulnerabilities to depression typically identifies factors that are
      thought to be universally maladaptive or adaptive. In contrast, researchers
      recently have theorized that the ability to flexibly engage in different thoughts
      and behaviors that fit situational demands may be most indicative of
      psychological health. We review empirical evidence from 147 studies reporting
      associations between five components of flexibility (set-shifting, affective set
      shifting, cardiac vagal control, explanatory flexibility, and coping flexibility)
      and depression and classify studies according to strength of study design.
      Evidence from correlational and case-controlled studies suggests cross-sectional
      relationships, but few prospective studies have been conducted. We discuss
      limitations of existing studies, identify new directions for programmatic
      research, and discuss implications that flexibility has for the prevention and
      treatment of depression.

PMID- 29038623
TI  - Wound Healing Concepts in Clinical Practice of OMFS.
AB  - BACKGROUND: Wound healing is a complex and dynamic process and a thorough
      knowledge of the basics of physiology of wound healing is a must to implement
      principles of chronic wound care. Understanding wound healing at multiple levels
      biochemical, physiologic, cellular and molecular provides the surgeon with a
      framework for basing clinical decisions aimed at optimizing the healing response.
      OBJECTIVE: This review article describes the classification of wounds and aims to
      highlight the fundamentals of wound repair, enumerating the dressings used
      commonly and also, the newer concepts of wound healing. MATERIALS AND METHODS:
      Search engines and medical databases were tapped to gather information on the
      subject. Search words employed were "Wounds", "wounds in OSMF", "Wound healing",
      "Repair", "Dressings in OMFS". RESULTS: The search resulted in total of 153
      articles which we reviewed to add to the literature the concepts of wound healing
      and to throw some light on recent advances in wound care. CONCLUSIONS: Wound
      healing remains a challenging clinical problem and correct, efficient wound
      management is essential to positively influence the wound healing course and
      reduce potential complications.

PMID- 29038625
TI  - Mucoepidermoid Carcinoma of the Salivary Glands: Survival and Prognostic Factors.
AB  - OBJECTIVE: The aim of this study was to establish global survival rates and
      potential prognostic factors for mucoepidermoid carcinoma (MC) of the salivary
      glands in patients diagnosed at the Dr. Eduardo Caceres Graziani National
      Institute for Neoplastic Diseases (INEN), Lima, Peru, between 2002 and 2012.
      MATERIALS AND METHODS: This was an observational, analytical and longitudinal
      (information reconstructed in time) retrospective cohort study. Data were
      obtained from clinical records and used to determine the overall survival (OS)
      rate at 2 and 5 years, and the individual percentage survival for each prognostic
      factor using the actuarial technique. We also performed univariate analysis for
      each possible prognostic factor using log-rank analysis, and multivariate
      analysis using Cox's regression model. The study was approved by the
      institutional review board at Dr. Eduardo Caceres Graziani INEN and conducted in
      accordance with the 1964 Declaration of Helsinki. For this type of study formal
      consent was not required. RESULTS: The OS rate of the 51 patients enrolled in the
      study was 81 % at 2 years and 78 % at 5 years. In the multivariate analysis, the
      equation that best explained the survival result contained the variable, clinical
      stage (p = 0.063). CONCLUSIONS: The results revealed the importance of clinical
      stage regarding the survival of patients with a primary diagnosis of MC of the
      salivary glands.

PMID- 29038626
TI  - Maxillofacial Injuries in Women: A Retrospective Study of 10 Years.
AB  - INTRODUCTION: Diversities exists in incidence, etiology and epidemiology of
      facial fractures among male and female individuals due to various reasons. Many
      of the epidemiological studies published during the millennium have shown male
      predilection. This study was carried to evaluate the etiology, patterns and
      distribution of facial fractures among different age groups in women. MATERIALS
      AND METHODS: This Retrospective epidemiological study dealt with a total of 302
      women with 422 fractures in maxillofacial region during a period of June 1st 2005
      to May 31st 2015 at Mamata Dental College and Hospital, Khammam, Telangana,
      India. RESULTS: Mean age of incidence was 31.58 years, mandibular fractures were
      highest (44.07 %) followed by zygomaticomaxillary complex injuries (ZMC) (20.37
      %). Road traffic accidents (RTA) injuries (53.7 %) were highest, followed by
      assault (23.9 %) and other causes. Highest number (33.8 %) of fractures were
      sustained in the 3rd decade and least (0.7 %) in the 8th decade of life. Among
      soft tissue injuries most commonly seen were lacerations (51 %). CONCLUSION:
      Results of this study suggest that there is an increase in the number of
      maxillofacial injuries in women, representing changes in the society, exposing
      women to similar conditions like men and increased number of working women. This
      study helps to identify trauma burden, assess the awareness of current preventive
      measures, women protection laws, for instituting new guidelines for prevention
      and planning health care services for women.

PMID- 29038627
TI  - Characterization and Antibiotic Sensitivity Profile of Bacteria in Orofacial
      Abscesses of Odontogenic Origin.
AB  - BACKGROUND: Odontogenic infections range from peripheral abscess to superficial
      and deep infections leading to severe infections in head and neck region. This
      study was aimed to assess bacterial isolates responsible for orofacial infection
      of odontogenic origin and their drug susceptibility patterns so as to provide
      better perceptive for the management of odontogenic infections. METHODS: The
      study was made in a selected cohort of patients, irrespective of age and gender
      having moderate and severe orofacial infections of odontogenic origin admitted to
      Yenepoya University Hospital. Pus samples were collected and identification of
      bacteria was performed by 16S rRNA gene sequencing. Antimicrobial susceptibility
      testing was performed by Kirby-Bauer disc diffusion method. RESULT: A total of 37
      study subjects were included, with bacterial isolation rate of 31 (83.7 %). The
      mean age presented of all patients was 40.62. Of all, 24 (64.9 %) were males.
      Staphylococcus aureus, Enterobacter claocae subsp. dissolvens, Klebsiella
      quasipneumoniae subsp. similipneumoniae, Staphylococcus aureus subsp. anaerobius
      and Klebsiella pneumoniae subsp. ozaenae were the most prevalent isolates. Result
      showed that 58.6 % of the isolates were resistant to gentamicin, 52.5 % for
      ampicillin, 51.3 % for piperacillin; least resistant being 18.9 % for
      azithromycin. CONCLUSION: High prevalence of bacterial isolates was found,
      Staphylococcus aureus being the dominant. Most of the bacteria were resistant to
      different classes of antibiotics. Appropriate antibiotics should be given based
      on the bacterial isolates, culture sensitivity and clinical course of the
      disease.

PMID- 29038628
TI  - Pre-operative Assessment of Anatomical Position of Inferior Alveolar Nerve and
      Its Significance in Bilateral Sagittal Split Osteotomy.
AB  - The aim of this study is to investigate the position and course of the mandibular
      canal through the ramus, angle and body of mandible using computed tomographic
      (CT) imaging pre-operatively and to relate these predetermined values intra
      operatively to perform sagittal split ramus osteotomies. Pre-operative CT scans
      were taken and four points were marked at mandibular foramen, mandibular angle,
      mandibular body and midpoint and different dimensions of IAN were measured to
      localize the inferior alveolar nerve. With the obtained values, precise osteotomy
      cuts were made intra-operatively and intra-operative measurements for position of
      IAN were noted. Based on the preoperative CT measurements, the chance to
      encounter IAN bundle, during surgery was evaluated. The present study proved that
      pre-operative CT imaging prior to BSSO surgical procedure is an effective way to
      investigate the position and course of the IAN canal through the framework of the
      mandible and by interpolating these dimensions intra operatively, reduces the
      risk of direct injury to the IAN bundle.

PMID- 29038629
TI  - Patient's Self-Assessment of Social-Approval After Mandibulectomy with
      Disarticulation: the Necessity for Jaw Reconstruction Following Loss of Facial
      Symmetry in a Resource-Poor African Setting.
AB  - OBJECTIVE: Mandibulectomy with disarticulation is usually carried out without
      reconstruction in Low-Income-Countries. Lower standards of living are usually
      acceptable and adapted to, in poor societies. This study compares patient's self
      assessment of social approval among reconstructed and non-reconstructed cases of
      mandibulectomy with disarticulation in a resource-poor African setting. MATERIAL
      AND METHOD: This questionnaire-based study documented patient's self-assessment
      of social approval of themselves following mandibulectomy with disarticulation.
      12 derived queries were administered on each patient, to test what they perceived
      of social acceptability of their facial features following mandibulectomy.
      RESULTS: All 10 patients who underwent mandibular reconstruction reported that
      they felt confident engaging in all forms of social activity, while all 10 who
      had resection without reconstruction did not. CONCLUSION: The low social approval
      perceived by patients who have undergone mandibulectomy with disarticulation
      without reconstruction necessitates that surgeons must strive to reconstruct this
      anatomical region even under circumstances of severe resource-constraint. The
      culture in the third-world is not supportive of patients who have not undergone
      reconstruction following resection, in spite of being victims of all-pervading
      poverty. LEVEL OF EVIDENCE: Level IV, investigative study.

PMID- 29038630
TI  - Effect of Alveolar Segmental Sandwich Osteotomy on Alveolar Height: A Preliminary
      Study.
AB  - PURPOSE: Bone loss following extraction is maximum in horizontal dimension.
      Height is also reduced which is pronounced on the buccal aspect. Various surgical
      procedures are available to correct the bone volume viz. GBR, onlay bone
      grafting, alveolar distraction and sandwich osteotomy. Sandwich osteotomy has
      been found to increase the vertical alveolar bone height successfully.
      OBJECTIVES: The objective of the study was to assess the effect of alveolar
      segmental sandwich osteotomy on alveolar height and crestal width. MATERIALS AND
      METHODOLOGY: A prospective study was undertaken from December 2012 to August
      2014. Seven patients with 12 implant sites with a mean age of 36 years were
      recruited. All seven patients with 12 implant sites underwent alveolar segmental
      sandwich osteotomy and interpositional bone grafting. Alveolar bone height was
      assessed radiographically preoperatively, immediate post-op, and at 3 months post
      op. Alveolar bone width was assessed radiographically preoperatively and at 3
      months post-op. Statistical significance was inferred at p < 0.05. RESULTS: The
      mean vertical augmentation at immediate post-op was 6.58 mm (p = 0.001). The
      vertical augmentation that was achieved 3 months post-op was a mean of 3.75 mm
      which was statistically significant (p = 0.004). The change in alveolar height
      from immediate post-op to 3 month post-op was a mean 1.69 mm. The mean change in
      alveolar crestal width at 3 months was a mean of -0.29 mm (p = 0.57). CONCLUSION:
      Sandwich osteotomy can be used as an alternative technique to increase alveolar
      bone height prior to implant placement. Moderate alveolar deficiency can be
      predictably corrected by this technique.

PMID- 29038631
TI  - Efficacy of Temporomandibular Joint Arthrocentesis with Sodium Hyaluronate in the
      Management of Temporomandibular Joint Disorders: A Prospective Randomized Control
      Trial.
AB  - PURPOSE: This study was designed to investigate the efficacy of the
      temporomandibular joint arthrocentesis with and without injection of sodium
      hyaluronate (SH) in the treatment of temporomandibular joint disorders. PATIENTS
      AND METHODS: A total of sixty two TMJs in 34 males and 28 females aged 20-65
      years comprised the study material. The patients' complaints were limited mouth
      opening, TMJ pain, and joint noises during function. Patients were randomly
      divided into 2 groups in which arthrocentesis plus intra-articular injection of
      sodium hyaluronate was performed in 1 group and only arthrocentesis was performed
      in the other group. Both groups contained patients with disc displacement with
      reduction and without reduction. Clinical evaluation of the patients was done
      before the procedure, immediately after the procedure, at 1 week and 1, 3 and 6
      months postoperatively. Intensity of TMJ pain was assessed using visual analog
      scales. Maximal mouth opening and lateral jaw movements also were recorded at
      each follow-up visit. RESULTS: Both techniques increased maximal mouth opening,
      lateral movements, and function, while reducing TMJ pain and noise. CONCLUSIONS:
      Although patients benefitted from both techniques, arthrocentesis with injection
      of SH seemed to be superior to arthrocentesis alone.

PMID- 29038632
TI  - Evaluation of Post-surgical Bacteremia with Use of Povidone-Iodine and
      Chlorhexidine During Mandibular Third Molar Surgery.
AB  - BACKGROUND: Microorganisms may invade the blood stream by oral routes through
      surgical procedures like extractions, fractured teeth and periodontal pockets.
      The incidence of bacteremia is 70-80 % following tooth extraction, sub gingival
      scaling and intra ligament injection. AIMS AND OBJECTIVES: Aim of study was to
      evaluate and compare the efficacy of two topical antimicrobial agents for the
      prevention of post-surgical bacteremia during mandibular third molar surgery. And
      objectives were to suggest need of proper topical antimicrobial agents and select
      proper antibiotics before oral surgical procedures in high risk cardiac patients.
      MATERIALS AND METHODS: Thirty patients with Class 1, Position B mesioangular
      impacted mandibular third molar were randomly included in study and divided into
      3 groups, each group containing 10 patients. Group I; sterile water group, Group
      II: povidone-iodine (5 %) group, Group III: chlorhexidine (Q, 2 %) group, pre and
      post-surgical blood samples were collected and Microbiological analyses of the
      blood samples were done. The organisms were identified by standard method on
      grams staining and identification of bacterial species by biochemical tests.
      RESULTS: The clinical parameters like oral hygiene index simplified and
      periodontal index of Russel showed that all patients in three groups had fair
      oral hygiene with simple gingivitis on mean. In some individuals with slightly
      higher OHIS and PI scores, bacteremia was noted. All the pre surgical blood
      samples were negative for the growth of bacteria after 7 days of culture. In
      total 30 patients, 12 subjects had postoperative bacteremia. Out of those 12
      patients 6 cases (60 %) of group I showed positive bacterial growth in the post
      surgical blood sample, while 4 cases in group III and 2 cases (20 %) in group II
      showed the same. CONCLUSION: Use of povidone-iodine and chlorhexidine prior to
      the oral surgical procedures decreases the incidence of bacteremia as compared to
      sterile water irrigation. Povidone-iodine significantly reduces the incidence
      bacteremia and number of organisms compared to chlorhexidine and sterile water.

PMID- 29038633
TI  - Comparison of Micromarsupialization and Modified Micromarsupialization for the
      Management of Mucocoele of Lower Lip: A Prospective Randomized Clinical Trial.
AB  - BACKGROUND: This study was undertaken to compare micromarsupialization and
      modified micromarsupialization for the management of mucoceles. MATERIALS AND
      METHODS: A prospective randomized clinical study was done on thirty patients
      having mucocele on lower lip. In Group A (n = 15), micromarsupialization and in
      Group B (n = 15), modified micromarsupialization technique was used. The outcome
      variables were duration of surgery, intraoperative pain, postoperative pain,
      healing and recurrence. t test and p values were used to compare the age,
      duration of lesion, duration of treatment and time taken for healing. The results
      were expressed as mean with SD. Statistical significance was established at the p
      <= 0.05 level. Analysis of pain (intraoperative, on 3rd, 7th day), intraoperative
      bleeding and recurrence was done using Fischer's exact test (p = 0.875, NS).
      RESULTS: The average duration of treatment for Group A was 4.10 +/- 0.39 min and
      for Group B was 5.33 +/- 0.2 min. The difference was found to be statistically
      highly significant (p value <=0.000). The observed power was 1.000. The
      difference in the intraoperative and postoperative pain on 3rd and 7th day was
      not found to be significant as per Fischer's exact test. The mean time taken for
      healing of the surgical site in Group A was 7.47 +/- 0.64 days and in Group B was
      9.87 +/- 1.88 days, and the difference was found to be highly significant. The
      observed power was 0.995. CONCLUSIONS: Modified micromarsupialization appears to
      be a safe technique for the management of mucoceles. However, in comparison with
      micromarsupialization, it has a higher operating and healing time.

PMID- 29038634
TI  - 3 Dimensional Plate in Management of Sagittal Palatal Fracture: A Novel
      Technique.
AB  - The palatal fracture is rare. There are varieties of techniques mentioned in the
      literature for fixation of palatal fracture. The management with Kirschner wire
      fixation, maxillary arch stabilization with the arch bars, trans-palatal, intra
      osseous, inter-molar, figure of eight wiring were technique sensitive and having
      poor patient compliance. We recommended the use of isolated 3 dimensional plate
      for fixation of sagittal palatal fracture.

PMID- 29038635
TI  - Pleomorphic Adenoma of Soft Palate: Unusual Occurrence of the Major Tumor in
      Minor Salivary Gland-A Case Report and Literature Review.
AB  - Salivary gland tumours constitute about less than 4 % of all head and neck
      tumours. Pleomorphic adenoma, also called benign mixed tumour, is the most common
      tumour of the salivary glands. About 80-90 % of these tumours occur in the major
      salivary glands mainly parotid gland and 10 % of them occur in the minor salivary
      glands. The most common site for pleomorphic adenoma of the minor salivary glands
      is the palate, followed by the lips and the cheeks. Other rare sites include the
      floor of the mouth, tongue, tonsil, pharynx, retromolar area and the nasal
      cavity. Here, we are reporting a case of pleomorphic adenoma of the minor
      salivary glands of the soft palate in a 36-year-old Indian female. The mass was
      removed by wide local excision with adequate margins under general anesthesia.
      There was no recurrence seen after a follow-up period of 1 year.

PMID- 29038636
TI  - Hybrid Implant: A Novel Implant System- Replica of BOI-BAC and BOI-BAC2.

PMID- 29038637
TI  - Subcuticular Suture Technique: Alternative to Frost Suture to Prevent Ectropion
      After Transcutaneous Incision of Lower Eyelid.
AB  - INTRODUCTION: An ectropion is a complication that can arise from reconstruction
      in the infraorbital region. Often, this complication occurs despite proper
      positioning of the lower lid at the time of closure. Various transcutaneous
      approaches to orbit skeleton have investigated in view of complication arising
      from them. A subtarsal approach with a postoperative Frost suture gives an
      advantage to reduce the occurrence of ectropion especially after treatment of
      orbital floor fractures. MATERIAL AND METHODS: This case describes a method of
      subcuticular suturing technique for subtarsal incision of lower lid which can be
      used to support the lid during healing period, thus decreasing the rate of
      ectropion. CONCLUSION: The technique described here is an alterative method for
      frost suturing with certain advantages.

PMID- 29038638
TI  - A Self-Retaining Lingual Flap Guarding Device During Surgical Removal of Impacted
      Mandibular Third Molar.
AB  - INTRODUCTION: Lingual nerve damage is one of the common complications following
      mandibular third molar surgery. On considering the impact of lingual nerve damage
      on the patient's quality of life, it is necessary to exercise caution to minimize
      its occurrence. MATERIAL AND METHODS: Although many lingual retractors are
      available, in this article we describe an indigenously designed lingual retractor
      for use in mandibular third molar surgery. CONCLUSION: The indigenous lingual
      retractor described in this article provides advantages like clear access and
      excellent retention unlike conventional retractors.

PMID- 29038639
TI  - Inductively-coupled Frequency Tuning and Impedance Matching in HTS-based NMR
      Probes.
AB  - Nuclear Magnetic Resonance (NMR) probes based on High Temperature Superconducting
      (HTS) resonators have demonstrated significant gains in detection sensitivity.
      However, the widespread acceptance of this technology has been limited by some
      unresolved issues including the mechanical unreliability of the moveable
      inductive loops used to adjust tuning and matching. In order to improve
      reliability, we propose to implement frequency tuning and impedance matching of
      HTS resonators using fixed inductively coupled loops and variable capacitors. By
      analyzing the loss mechanisms associated with inductive loops, we predict that
      using a superconducting inductive loop for tuning and matching will not only
      improve the reliability of HTS probes, but also provide improvements in
      sensitivity.

PMID- 29038640
TI  - A Liquid Optical Phase Shifter with an Embedded Electrowetting Actuator.
AB  - We demonstrate an electrowetting-based liquid optical phase shifter. The phase
      shifter consists of two immiscible liquid layers with different refractive
      indices. Sandwiched between the two liquids is a rigid membrane that moves freely
      along the optical axis and supported by a compliant surround. When applied with a
      pressure, the thicknesses of both liquid layers change, which induces a
      difference in optical path, resulting in a phase shift. A miniaturized
      electrowetting-based actuator is used to produce hydraulic pressure. A multi
      layered SU8 bonded structure was fabricated. A phase shift of 171 degrees  was
      observed when the device was incorporated in a Mach-Zehnder interferometer and
      driven with 100 V.

PMID- 29038642
TI  - Diagnosing and Treating Eosinophilic Esophagitis.

PMID- 29038641
TI  - A Method for Mapping Glycosylation Sites in Proteins.
AB  - The analysis of protein glycosylation by mass spectrometry (MS) has been a
      challenging technical problem. Quantification by HPLC of N-linked glycans can be
      executed by the use of peptide-N-glycosidase F to release them from the protein,
      followed by attachment of a fluorescent label and subsequent fluorescence
      detection. Similar quantification of O-linked glycans is not possible, as a
      result of the lack of a universal deglycosylation enzyme. Site-specific analyses
      by MS, such as the use of proteases to digest the glycoprotein, are difficult to
      use for quantification of glycans, as a result of the presence of miscleavages.
      Here, we present a new application of a digestion method for native proteins
      using resin-bound, thermally stabilized proteases. The use of this enzymatic
      treatment eliminates miscleavages around the site of glycosylation, thereby
      allowing site-specific relative quantification of glycans on glycoproteins. A
      native, intact human mAb was digested using a thermally stable, resin-bound
      trypsin to produce glycopeptides from the Fc region using a single-step protocol.
      A 1 mg sample was treated with 60 ug trypsin for 3 h at 70 degrees C. After
      digestion, acetonitrile was added, and the mixture was centrifuged to remove the
      resin before analysis. Liquid chromatography (LC)/MS with hydrophilic interaction
      chromatography was used to analyze the glycopeptides produced. All of the
      glycopeptides found resulted from a single peptide (EEQYNSTYR). The LC/MS
      analysis of the glycopeptides is compared with that of fluorescently labeled
      glycans. Quantitative analysis produced a correlation coefficient of 0.87 for the
      linear fit between the glycopeptide and released glycan methods.

PMID- 29038644
TI  - Black Box Warning for Possible HBV Reactivation During DAA Therapy for Chronic
      HCV Infection.
AB  - In 2016, the US Food and Drug Administration issued a warning about the risk of
      hepatitis B virus (HBV) reactivation in some patients receiving direct-acting
      antiviral (DAA) therapy for hepatitis C virus (HCV) infection. HBV reactivation
      can occur soon after the start of DAA therapy; thus, monitoring liver enzymes
      during DAA therapy is important in patients at risk. The clinical outcomes of HBV
      reactivation in this patient population may resemble the outcomes seen in
      immunosuppressed patients receiving chemotherapy. Each drug combination regimen
      has demonstrated risk for HBV reactivation and, therefore, contains a black box
      warning stating that all HCV-infected patients pending treatment should be tested
      for evidence of current or prior infection with HBV before initiating treatment.
      Both the American Association for the Study of Liver Diseases and the European
      Association for the Study of the Liver guidelines have been updated accordingly.

PMID- 29038645
TI  - Managing Obesity With Endoscopic Sleeve Gastroplasty.

PMID- 29038643
TI  - Current Diagnostic and Treatment Strategies for Eosinophilic Esophagitis.
AB  - Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the
      esophagus diagnosed by the presence of esophageal symptoms accompanied by an
      esophageal eosinophilic infiltrate. EoE has an increasing worldwide prevalence
      and can be a cause of dysphagia and food impactions. There is an important role
      for the use of proton pump inhibitors in the diagnostic pathway of EoE. Treatment
      paradigms for EoE aim to minimize esophageal inflammation and improve symptom
      control. Dietary therapy targets dietary allergens and encompasses the elemental
      diet, the allergy testing-directed elimination diet, and the empiric elimination
      diet. Pharmacologic options include topical corticosteroids as the standard first
      line treatment. Multiple other pharmacologic interventions are currently under
      investigation and are not recommended in the most recent guidelines. Endoscopic
      dilation is usually reserved for patients who relapse on pharmacologic or dietary
      regimens or who have symptomatic stricturing disease. This article provides a
      comprehensive discussion of existing diagnostic and management strategies for
      EoE.

PMID- 29038646
TI  - Medical Therapies in the Pipeline for Irritable Bowel Syndrome.

PMID- 29038647
TI  - Extrahepatic Benefits Achieved With Sustained Virologic Response in Patients With
      Hepatitis C Virus Infection.

PMID- 29038649
TI  - GASTRO-HEP News.

PMID- 29038648
TI  - Overview of Therapeutic Drug Monitoring of Biologic Agents in Patients With
      Inflammatory Bowel Disease.

PMID- 29038650
TI  - Kinship Support in Jamaican Families in the USA and Jamaica.

PMID- 29038651
TI  - Classification of Suicide Attempts through a Machine Learning Algorithm Based on
      Multiple Systemic Psychiatric Scales.
AB  - Classification and prediction of suicide attempts in high-risk groups is
      important for preventing suicide. The purpose of this study was to investigate
      whether the information from multiple clinical scales has classification power
      for identifying actual suicide attempts. Patients with depression and anxiety
      disorders (N = 573) were included, and each participant completed 31 self-report
      psychiatric scales and questionnaires about their history of suicide attempts. We
      then trained an artificial neural network classifier with 41 variables (31
      psychiatric scales and 10 sociodemographic elements) and ranked the contribution
      of each variable for the classification of suicide attempts. To evaluate the
      clinical applicability of our model, we measured classification performance with
      top-ranked predictors. Our model had an overall accuracy of 93.7% in 1-month,
      90.8% in 1-year, and 87.4% in lifetime suicide attempts detection. The area under
      the receiver operating characteristic curve (AUROC) was the highest for 1-month
      suicide attempts detection (0.93), followed by lifetime (0.89), and 1-year
      detection (0.87). Among all variables, the Emotion Regulation Questionnaire had
      the highest contribution, and the positive and negative characteristics of the
      scales similarly contributed to classification performance. Performance on
      suicide attempts classification was largely maintained when we only used the top
      five ranked variables for training (AUROC; 1-month, 0.75, 1-year, 0.85, lifetime
      suicide attempts detection, 0.87). Our findings indicate that information from
      self-report clinical scales can be useful for the classification of suicide
      attempts. Based on the reliable performance of the top five predictors alone,
      this machine learning approach could help clinicians identify high-risk patients
      in clinical settings.

PMID- 29038652
TI  - Hierarchical Recursive Organization and the Free Energy Principle: From
      Biological Self-Organization to the Psychoanalytic Mind.
AB  - The present paper argues that a systems theory epistemology (and particularly the
      notion of hierarchical recursive organization) provides the critical theoretical
      context within which the significance of Friston's (2010a) Free Energy Principle
      (FEP) for both evolution and psychoanalysis is best understood. Within this
      perspective, the FEP occupies a particular level of the hierarchical organization
      of the organism, which is the level of biological self-organization. This form of
      biological self-organization is in turn understood as foundational and pervasive
      to the higher levels of organization of the human organism that are of interest
      to both neuroscience as well as psychoanalysis. Consequently, central
      psychoanalytic claims should be restated, in order to be located in their proper
      place within a hierarchical recursive organization of the (situated) organism. In
      light of the FEP the realization of the psychoanalytic mind by the brain should
      be seen in terms of the evolution of different levels of systematic organization
      where the concepts of psychoanalysis describe a level of hierarchical recursive
      organization superordinate to that of biological self-organization and the FEP.
      The implication of this formulation is that while "psychoanalytic" mental
      processes are fundamentally subject to the FEP, they nonetheless also add their
      own principles of process over and above that of the FEP. A model found in
      Grobbelaar (1989) offers a recursive bottom-up description of the self
      organization of the psychoanalytic ego as dependent on the organization of
      language (and affect), which is itself founded upon the tendency toward
      autopoiesis (self-making) within the organism, which is in turn described as
      formally similar to the FEP. Meaningful consilience between Grobbelaar's model
      and the hierarchical recursive description available in Friston's (2010a) theory
      is described. The paper concludes that the valuable contribution of the FEP to
      psychoanalysis underscores the necessity of reengagement with the core concepts
      of psychoanalytic theory, and the usefulness that a systems theory epistemology
      particularly hierarchical recursive description-can have for this goal.

PMID- 29038653
TI  - Editorial: Inflammation in the CNS: Advancing the Field Using Intravital Imaging.

PMID- 29038654
TI  - CpG-ODN Facilitates Effective Intratracheal Immunization and Recall of Memory
      against Neoantigen-Expressing Alveolar Cells.
AB  - Intrapulmonary immune reactions are impaired by the tolerogenic environment of
      the lung. This is manifested by the absence of effective endogenous T cell
      responses upon neoantigen expression. This tolerance is considered to contribute
      to lung cancer and inefficient immune therapeutic interventions. To investigate
      the mechanisms contributing to lung tolerance and to overcome these restrictions,
      we developed a transgenic mouse model with induction of a neoantigen (OVA)
      exclusively in alveolar type II epithelial cells. This model is characterized by
      the absence of functional endogenous T cell responses upon OVA neoantigen
      induction. Standard DNA and protein vaccination protocols resulted in the
      accumulation of high numbers of antigen-specific CD8 T cells in the lung.
      However, clearance of antigen-expressing cells was not achieved. To overcome this
      tolerance, we induced inflammatory conditions by coapplication of the TLR ligands
      LPS and CpG-ODN during intrapulmonary vaccinations. Both ligands induced high
      numbers of neoantigen-specific T cells in the lung. However, only coapplication
      of CpG-ODN was sufficient to establish functional cytotoxic responses resulting
      in the elimination of neoantigen presenting target cells. Remarkably, CpG-ODN was
      also crucial for functional memory responses upon re-induction of the neoantigen.
      The results highlight the need of TLR9 co-stimulation for overcoming
      tolerization, which might be a key factor for therapeutic interventions.

PMID- 29038655
TI  - Editorial: Induction of Central Nervous System Disease by the Adaptive Immune
      Response.

PMID- 29038656
TI  - Unveiling a Drift Resistant Cryptotope within Marburgvirus Nucleoprotein
      Recognized by Llama Single-Domain Antibodies.
AB  - Marburg virus (MARV) is a highly lethal hemorrhagic fever virus that is
      increasingly re-emerging in Africa, has been imported to both Europe and the US,
      and is also a Tier 1 bioterror threat. As a negative sense RNA virus, MARV has
      error prone replication which can yield progeny capable of evading
      countermeasures. To evaluate this vulnerability, we sought to determine the
      epitopes of 4 llama single-domain antibodies (sdAbs or VHH) specific for
      nucleoprotein (NP), each capable of forming MARV monoclonal affinity reagent
      sandwich assays. Here, we show that all sdAb bound the C-terminal region of NP,
      which was produced recombinantly to derive X-ray crystal structures of the three
      best performing antibody-antigen complexes. The common epitope is a trio of alpha
      helices that form a novel asymmetric basin-like depression that accommodates each
      sdAb paratope via substantial complementarity-determining region (CDR)
      restructuring. Shared core contacts were complemented by unique accessory
      contacts on the sides and overlooks of the basin yielding very different approach
      routes for each sdAb to bind the antigen. The C-terminal region of MARV NP was
      unable to be crystallized alone and required engagement with sdAb to form
      crystals suggesting the antibodies acted as crystallization chaperones. While
      gross structural homology is apparent between the two most conserved helices of
      MARV and Ebolavirus, the positions and morphologies of the resulting basins were
      markedly different. Naturally occurring amino acid variations occurring in bat
      and human Marburgvirus strains all mapped to surfaces distant from the predicted
      sdAb contacts suggesting a vital role for the NP interface in virus replication.
      As an essential internal structural component potentially interfacing with a
      partner protein it is likely the C-terminal epitope remains hidden or "cryptic"
      until virion disruption occurs. Conservation of this epitope over 50 years of
      Marburgvirus evolution should make these sdAb useful foundations for diagnostics
      and therapeutics resistant to drift.

PMID- 29038657
TI  - Platelet-Derived Chemokine CXCL7 Dimer Preferentially Exists in the
      Glycosaminoglycan-Bound Form: Implications for Neutrophil-Platelet Crosstalk.
AB  - Platelet-derived chemokine CXCL7 (also known as NAP-2) plays a crucial role in
      orchestrating neutrophil recruitment in response to vascular injury. CXCL7 exerts
      its function by activating the CXC chemokine receptor 2 (CXCR2) receptor and
      binding sulfated glycosaminoglycans (GAGs) that regulate receptor activity. CXCL7
      exists as monomers, dimers, and tetramers, and previous studies have shown that
      the monomer dominates at lower and the tetramer at higher concentrations. These
      observations then raise the question: what, if any, is the role of the dimer? In
      this study, we make a compelling observation that the dimer is actually the
      favored form in the GAG-bound state. Further, we successfully characterized the
      structural basis of dimer binding to GAG heparin using solution nuclear magnetic
      resonance (NMR) spectroscopy. The chemical shift assignments were obtained by
      exploiting heparin binding-induced NMR spectral changes in the WT monomer and
      dimer and also using a disulfide-linked obligate dimer. We observe that the
      receptor interactions of the dimer are similar to the monomer and that heparin
      bound dimer is occluded from receptor interactions. Cellular assays also show
      that the heparin-bound CXCL7 is impaired for CXCR2 activity. We conclude that the
      dimer-GAG interactions play an important role in neutrophil-platelet crosstalk,
      and that these interactions regulate gradient formation and the availability of
      the free monomer for CXCR2 activation and intrathrombus neutrophil migration to
      the injury site.

PMID- 29038658
TI  - The Peyer's Patch Mononuclear Phagocyte System at Steady State and during
      Infection.
AB  - The gut represents a potential entry site for a wide range of pathogens including
      protozoa, bacteria, viruses, or fungi. Consequently, it is protected by one of
      the largest and most diversified population of immune cells of the body. Its
      surveillance requires the constant sampling of its encounters by dedicated
      sentinels composed of follicles and their associated epithelium located in
      specialized area. In the small intestine, Peyer's patches (PPs) are the most
      important of these mucosal immune response inductive sites. Through several
      mechanisms including transcytosis by specialized epithelial cells called M-cells,
      access to the gut lumen is facilitated in PPs. Although antigen sampling is
      critical to the initiation of the mucosal immune response, pathogens have evolved
      strategies to take advantage of this permissive gateway to enter the host and
      disseminate. It is, therefore, critical to decipher the mechanisms that underlie
      both host defense and pathogen subversive strategies in order to develop new
      mucosal-based therapeutic approaches. Whereas penetration of pathogens through M
      cells has been well described, their fate once they have reached the
      subepithelial dome (SED) remains less well understood. Nevertheless, it is clear
      that the mononuclear phagocyte system (MPS) plays a critical role in handling
      these pathogens. MPS members, including both dendritic cells and macrophages, are
      indeed strongly enriched in the SED, interact with M cells, and are necessary for
      antigen presentation to immune effector cells. This review focuses on recent
      advances, which have allowed distinguishing the different PP mononuclear
      phagocyte subsets. It gives an overview of their diversity, specificity,
      location, and functions. Interaction of PP phagocytes with the microbiota and the
      follicle-associated epithelium as well as PP infection studies are described in
      the light of these new criteria of PP phagocyte identification. Finally, known
      alterations affecting the different phagocyte subsets during PP stimulation or
      infection are discussed.

PMID- 29038659
TI  - In Silico Prediction Analysis of Idiotope-Driven T-B Cell Collaboration in
      Multiple Sclerosis.
AB  - Memory B cells acting as antigen-presenting cells are believed to be important in
      multiple sclerosis (MS), but the antigen they present remains unknown. We
      hypothesized that B cells may activate CD4+ T cells in the central nervous system
      of MS patients by presenting idiotopes from their own immunoglobulin variable
      regions on human leukocyte antigen (HLA) class II molecules. Here, we use
      bioinformatics prediction analysis of B cell immunoglobulin variable regions from
      11 MS patients and 6 controls with other inflammatory neurological disorders
      (OINDs), to assess whether the prerequisites for such idiotope-driven T-B cell
      collaboration are present. Our findings indicate that idiotopes from the
      complementarity determining region (CDR) 3 of MS patients on average have high
      predicted affinities for disease associated HLA-DRB1*15:01 molecules and are
      predicted to be endosomally processed by cathepsin S and L in positions that
      allows such HLA binding to occur. Additionally, complementarity determining
      region 3 sequences from cerebrospinal fluid (CSF) B cells from MS patients
      contain on average more rare T cell-exposed motifs that could potentially escape
      tolerance and stimulate CD4+ T cells than CSF B cells from OIND patients. Many of
      these features were associated with preferential use of the IGHV4 gene family by
      CSF B cells from MS patients. This is the first study to combine high-throughput
      sequencing of patient immune repertoires with large-scale prediction analysis and
      provides key indicators for future in vitro and in vivo analyses.

PMID- 29038660
TI  - Genetic Regulation of GA Metabolism during Vernalization, Floral Bud Initiation
      and Development in Pak Choi (Brassica rapa ssp. chinensis Makino).
AB  - Pak choi (Brassica rapa ssp. chinensis Makino) is a representative seed
      vernalization vegetable and premature bolting in spring can cause significant
      economic loss. Thus, it is critical to elucidate the mechanism of molecular
      regulation of vernalization and floral bud initiation to prevent premature
      bolting. Gibberellin (GA) is the key plant hormone involved in regulating plant
      development. To gain a better understanding of GA metabolism in pak choi, the
      content of GA in pak choi was measured at different stages of plant development
      using enzyme-linked immunosorbent assay. The results showed that the GA content
      increased significantly after low-temperature treatment (4 degrees C) and then
      decreased rapidly with vegetative growth. During floral bud initiation, the GA
      content increased rapidly until it peaked upon floral bud differentiation. To
      elucidate these changes in GA content, the expression of homologous genes
      encoding enzymes directly involved in GA metabolism were analyzed. The results
      showed that the changes in the expression of four genes involved in GA synthesis
      (Bra035120 encoding ent-kaurene synthase, Bra009868 encoding ent-kaurene oxidase,
      Bra015394 encoding ent-kaurenoic acid oxidase, and Bra013890 encoding GA20
      oxidase) were correlated with the changes in GA content. In addition, by
      comparing the expression of genes involved in GA metabolism at different growth
      stages, seven differentially expressed genes (Bra005596, Bra009285, Bra022565,
      Bra008362, Bra033324, Bra010802, and Bra030500) were identified. The differential
      expression of these genes were directly correlated with changes in GA content,
      suggesting that these genes were directly related to vernalization, floral bud
      initiation and development. These results contribute to the understanding of the
      molecular mechanism of changes in GA content during different developmental
      phases in pak choi.

PMID- 29038661
TI  - Assembly and Annotation of Transcriptome Provided Evidence of miRNA Mobility
      between Wheat and Wheat Stem Sawfly.
AB  - Wheat Stem Sawfly (WSS), Cephus Cinctus Norton (Hymenoptera: Cephidae), is one of
      the most important pests, causing yield and economic losses in wheat and barley.
      The lack of information about molecular mechanisms of WSS for defeating plant's
      resistance prevents application of effective pest control strategies therefore,
      it is essential to identify the genes and their regulators behind WSS
      infestations. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are
      recognized with their regulatory functions on gene expression, tuning protein
      production by controlling transcriptional and post-transcriptional activities. A
      transcriptome-guided approach was followed in order to identify miRNAs, lncRNAs,
      and mRNA of WSS, and their interaction networks. A total of 1,893 were presented
      here as differentially expressed between larva and adult WSS insects. There were
      11 miRNA families detected in WSS transcriptome. Together with the annotation of
      1,251 novel mRNAs, the amount of genetic information available for WSS was
      expanded. The network between WSS miRNAs, lncRNAs, and mRNAs suggested miRNA
      mediated regulatory roles of lncRNAs as competing endogenous RNAs. In the light
      of the previous evidence that small RNA molecules of a pathogen could suppress
      the immune response of host plant, we analyzed the putative interactions between
      larvae and wheat at the miRNA level. Overall, this study provides a profile of
      larva and adult WSS life stages in terms of coding and non-coding elements. These
      findings also emphasize the potential roles of wheat and larval miRNAs in wheat
      resistance to infestation and in the suppression of resistance which is critical
      for the development of effective pest control strategies.

PMID- 29038662
TI  - Multidrug Resistant Enteric Bacterial Pathogens in a Psychiatric Hospital in
      Ghana: Implications for Control of Nosocomial Infections.
AB  - Enteric bacteria are commonly implicated in hospital-acquired or nosocomial
      infections. In Ghana, these infections constitute an important public health
      problem but little is known about their contribution to antibiotic resistance.
      The aim of the study was to determine the extent and pattern of antibiotic
      resistance of enteric bacteria isolated from patients and environmental sources
      at the Accra Psychiatric Hospital. A total of 265 samples were collected from the
      study site including 142 stool and 82 urine samples from patients, 7 swab samples
      of door handle, and 3 samples of drinking water. Enteric bacteria were isolated
      using standard microbiological methods. Antibiograms of the isolates were
      determined using the disc diffusion method. Overall, 232 enteric bacteria were
      isolated. Escherichia coli was the most common (38.3%), followed by Proteus
      (19.8%), Klebsiella (17.7%), Citrobacter (14.7%), Morganella (8.2%), and
      Pseudomonas (1.3%). All isolates were resistant to ampicillin but sensitive to
      cefotaxime. The resistance ranged from 15.5% to 84.5%. Multidrug resistance was
      most prevalent (100%) among isolates of Proteus and Morganella and least
      prevalent among isolates of Pseudomonas (33.3%). Multidrug resistance among
      enteric bacteria at the study hospital is high and hence there is a need for
      screening before therapy to ensure prudent use of antibiotics.

PMID- 29038663
TI  - Repetition Blindness for Faces: A Comparison of Face Identity, Expression, and
      Gender Judgments.
AB  - Repetition blindness (RB) refers to the impairment in reporting two identical
      targets within a rapid serial visual presentation stream. While numerous studies
      have demonstrated RB for words and picture of objects, very few studies have
      examined RB for faces. This study extended this research by examining RB when the
      two faces were complete repeats (same emotion and identity), identity repeats
      (same individual, different emotion), and emotion repeats (different individual,
      same emotion) for identity, gender, and expression judgment tasks. Complete RB
      and identity RB effects were evident for all three judgment tasks. Emotion RB was
      only evident for the expression and gender judgments. Complete RB effects were
      larger than emotion or identity RB effects across all judgment tasks. For the
      expression judgments, there was more emotion than identity RB. The identity RB
      effect was larger than the emotion RB effect for the gender judgments. Cross task
      comparisons revealed larger complete RB effects for the expression and gender
      judgments than the identity decisions. There was a larger emotion RB effect for
      the expression than gender judgments and the identity RB effect was larger for
      the gender than for the identity and expression judgments. These results indicate
      that while faces are subject to RB, this is affected by the type of repeated
      information and relevance of the facial characteristic to the judgment decision.
      This study provides further support for the operation of separate processing
      mechanisms for face gender, emotion, and identity information within models of
      face recognition.

PMID- 29038664
TI  - Trypophobic Discomfort is Spatial-Frequency Dependent.
AB  - Clusters of holes, such as those in a lotus seedpod, induce trypophobic
      discomfort. Previous research has demonstrated that high-contrast energy at
      midrange spatial frequencies in images causes trypophobic discomfort. The present
      study examined the effects on discomfort of eliminating various spatial frequency
      components from the images to reveal how each spatial frequency contributes to
      the discomfort. Experiment 1 showed that eliminating midrange spatial frequencies
      did not affect trypophobic discomfort, while Experiment 2 revealed that images of
      holes that consisted of only high-spatial frequencies evoked less discomfort than
      other images and that images containing only low or midrange spatial frequencies
      induced as much trypophobic discomfort as did the original images. Finally,
      Experiment 3 found that participants with a high level of the trypophobic trait
      experienced stronger discomfort from the original images and the images
      containing only low or midrange spatial frequencies than participants with a low
      level of the trypophobic trait. Our findings thus suggest that trypophobic
      discomfort can be induced by middle and low spatial frequencies.

PMID- 29038665
TI  - C-Reactive Protein as an Independent Cardiovascular Risk Predictor in HIV+
      Patients: A Focused Review of Published Studies.
AB  - Patients infected with the human immunodeficiency virus (HIV+) are living longer
      and at heightened risk for developing cardiovascular events (CVEs). Commonly used
      prediction tools appear to misrepresent their CVE risk to varying degrees and in
      varying directions. Inclusion of markers of cellular infection, chronic immune
      activation and/or systemic inflammation into risk models might provide better
      predictive accuracy. Observational studies assessing the relationship of high
      sensitivity C-reactive protein (hs-CRP) to CVE in HIV+ patients have reported
      inconsistent findings. This review of published studies attempted to determine if
      the available evidence supports its potential use in new models for stable,
      treated HIV+ patients. We searched the PubMed database using keywords and
      combinations of "HIV" AND "cardiovascular risk" AND "CRP". Papers presenting
      original analyses, associating hs-CRP concentration as an independent variable to
      hard cardiovascular outcomes (myocardial infarction and cardiovascular death), or
      to hard CVE as part of a composite endpoint, were included. Five observational
      studies met inclusion/exclusion criteria for review. Three papers identified an
      association between elevated hs-CRP and CVE, while two others failed to find any
      significant association. All reports were heterogeneous in terms of independent
      variables, controls, and designs. The larger and more rigorous studies, employing
      higher rates of confounder controls and more objective endpoints in their
      composites, showed positive associations. Though not conclusive, the
      preponderance of the evidence at this time supports CRP as a potentially valuable
      factor to be studied in prospective cardiovascular risk prediction investigations
      in HIV+ patients.

PMID- 29038666
TI  - Study of Methylene Blue Ototoxicity in the Guinea Pig.
AB  - BACKGROUND: Methylene blue is widely used in the medical field, especially as a
      blue dye for staining. It is also used as a photosensitizing agent in
      antimicrobial photodynamic therapy, which once photoactivated is effective for
      the eradication of several multi-resistant bacteria. The objective of this study
      was to investigate the ototoxic potential of methylene blue and precise its use
      in otology. METHODS: It was a prospective animal study performed on guinea pigs
      in our tertiary medical center. We divided the animals into two groups: an
      experimental group and a control group, who underwent a series of three
      intratympanic (IT) injections. In the control group (n = 10), they received
      injections of gentamicin in one ear (positive control) and normal saline in the
      contralateral ear (negative control). The experimental group (n = 10) received
      injections of methylene blue in one ear, compared to injections of normal saline
      in the contralateral ear. We conducted auditory-evoked brainstem response (ABR)
      before and 1 week after the injection series. Once this is completed, the cochlea
      was dissected and caspase-3 was analyzed by immunohistochemistry. RESULTS: The
      mean difference of hearing loss in the methylene blue group compared to normal
      saline was 1.50 dB, and it was not shown to be statistically significant (P =
      0.688). For the positive control group, which received IT injections of
      gentamicin, the mean threshold of hearing loss difference for all the frequencies
      combined was 66.25 dB (P < 0.001). Furthermore, uptake of caspase-3 by
      immunohistochemistry (apoptotic marker) was negative in our group, which received
      injections of methylene blue. CONCLUSION: In light of our results, IT injections
      of methylene blue did not demonstrate an ototoxic potential. We recommend further
      studies to precise its use in the otologic field.

PMID- 29038667
TI  - Predicting Mortality of Patients With Sepsis: A Comparison of APACHE II and
      APACHE III Scoring Systems.
AB  - BACKGROUND: Acute Physiology, Age and Chronic Health Evaluation (APACHE) II and
      III scores were developed in 1985 and 1991, respectively, and are used mainly for
      critically ill patients of all disease categories admitted to the intensive care
      unit (ICU). They differ in how chronic health status is assessed, in the number
      of physiologic variables included (12 vs. 17), and in the total score. These two
      scoring systems have not been compared in predicting hospital mortality in
      patients with sepsis. METHODS: We retrospectively identified all septic patients
      admitted to our 54-bed medical-surgical ICU between June 2009 and February 2014
      using the APACHE outcomes database. We calculated correlation coefficients for
      APACHE II and APACHE III scores in predicting hospital mortality. Receiver
      operating characteristic (ROC) curves were also used to assess the mortality
      predictions. RESULTS: We identified a total of 2,054 septic patients. Average
      APACHE II score was 19 +/- 7, and average APACHE III score was 68 +/- 28. ICU
      mortality was 11.8% and hospital mortality was 18.3%. Both APACHE II (r = 0.41)
      and APACHE III scores (r = 0.44) had good correlations with hospital mortality.
      There was no statistically significant difference between the two correlations (P
      = 0.1). ROC area under the curve (AUC) was 0.80 (95% confidence interval (CI):
      0.78 - 0.82) for APACHE II, and 0.83 (95% CI: 0.81 - 0.85) for APACHE III,
      suggesting that both scores have very good discriminative powers for predicting
      hospital mortality. CONCLUSIONS: This study shows that both APACHE II and APACHE
      III scores in septic patients were very strong predictors of hospital mortality.
      APACHE II was as good as APACHE III in predicting hospital mortality in septic
      patients.

PMID- 29038668
TI  - Overcrowding and Its Association With Patient Outcomes in a Median-Low Volume
      Emergency Department.
AB  - BACKGROUND: Crowding occurs commonly in high volume emergency departments (ED)
      and has been associated with negative patient care outcomes. We aim to assess ED
      crowding in a median-low volume setting and evaluate associations with patient
      care outcomes. METHODS: This was a prospective single-center study from November
      14, 2016 until December 14, 2016. ED crowding was measured every 2 h by three
      different estimation tools: National Emergency Department Overcrowding Score
      (NEDOCS); Community Emergency Department Overcrowding Score (CEDOCS); and
      Severely-overcrowding Overcrowding and Not-overcrowding Estimation Tool (SONET)
      categorized under six different levels of crowding (not busy, busy, extremely
      busy, overcrowded, severely overcrowded, and dangerously overcrowded). Crowding
      scores were assigned to each patient upon ED arrival. We evaluated the
      distributions of crowding and patient ED length of stay (ED LOS) across
      estimation tools. Accelerated failure time models were utilized to estimate time
      ratios and their corresponding 95% confidence intervals comparing median LOS
      across levels of crowding within each estimation tool. RESULTS: This study
      comprised 2,557 patients whose median ED LOS was 150 min. Approximately 2% of
      patients arrived during 2 h time intervals deemed overcrowded regardless of the
      crowding tool used. Median ED LOS increased with the increased level of ED
      crowding and prolonged median ED LOS (> 150 min) occurred at ED of extremely busy
      status. Time ratios ranged from 1.09 to 1.48 for NEDOCS, 1.25 - 1.56 for CEDOCS,
      and 1.26 - 1.72 for SONET. CONCLUSION: Overcrowding rarely occurred in study ED
      with median-low annual volume and might not be a valuable marker for ED crowding
      report. Though similar patterns of prolonged ED LOS occurred with increased
      levels of ED crowding, it seems crowding alerts should be initiated during
      extremely busy status in this ED setting.

PMID- 29038669
TI  - Body Composition Is Altered in Pre-Diabetic Patients With Impaired Fasting
      Glucose Tolerance: Results From the NHANES Survey.
AB  - BACKGROUND: Previous studies suggest that type 2 diabetes mellitus (T2DM) is
      associated with a loss of muscle mass but the impact of fasting blood glucose
      (FBG) on body composition remains underappreciated in pre-diabetic subjects. The
      aim of this study was to determine the influence of FBG on lean mass (LM), fat
      mass (FM) and their distribution (trunk vs. appendicular), separately in middle
      aged men and women. METHODS: One thousand nine hundred and eleven (1,911) men
      (63.9 +/- 11.7 years) and 1,977 women (63.7 +/- 12.1 years) from the National
      Health and Nutrition Examination Survey (1999 - 2004) were divided into four
      groups: normal glucose tolerance (NGT), low impaired fasting glucose (IFG), high
      IFG and T2DM. Body composition was obtained from dual X-ray absorptiometry (DXA).
      RESULTS: Of the patients, 68.7% had NGT, 16.1% low IFG, 9.4% high IFG and 5.8%
      T2DM. After adjustment for age, body mass index, ethnicity, smoking, alcohol and
      physical activity (PA), no change in appendicular LM was observed between groups,
      but significant increases in trunk FM (in both gender) and trunk LM (in women)
      were found with increased glucose intolerance (T2DM > IFG > NGT), as well as
      significant decreases in trunk and total LM/FM ratios (T2DM < IFG < NGT) and a
      significant increase in trunk/appendicular FM ratio (T2DM > IFG > NGT).
      CONCLUSIONS: Elevated FBG within the normal range is not associated with a
      significant loss of appendicular LM, but modifications in LM and FM trunk and
      total distribution with IFG suggest that nutritional and physical lifestyle
      strategies should be implemented in the pre-diabetic state.

PMID- 29038670
TI  - Can Total Body Resistance Measured Using Bioelectrical Impedance Analysis Be the
      Index of Dehydration in Older Japanese Patients?
AB  - BACKGROUND: Dehydration in older patients has long been considered a significant
      health problem because it implies increased morbidity and mortality. However,
      dehydration is detected by a combination of physical signs and blood tests. For
      older people dwelling at home and in nursing homes, a simple and non-invasive
      method for detecting dehydration by caregivers is needed. The total body
      resistance is measured using bioelectrical impedance analysis and is known as an
      indicator of dehydration. There are no data from older Japanese patients on this
      issue. We performed this study to examine the relationship between dehydration
      and total body resistance in Japan. METHODS: We performed blood tests and
      measured bioelectrical impedance in older outpatients aged >= 65 years from the
      Internal Medicine Department at Mito Kyodo General Hospital. Patients were
      classified as dehydrated and non-dehydrated using the dehydration index with a
      blood urea nitrogen/creatinine ratio > 20, and the mean total body resistance was
      compared between the two groups. RESULTS: Eighty-one patients were recruited in
      the study. In the dehydrated group, the mean total body resistance was 439 Omega
      at 50 kHz, which was significantly higher than that in the non-dehydrated group
      (408 Omega, P = 0.038). CONCLUSIONS: The total body resistance measurements can
      be used for simple assessment of dehydration among older Japanese patients.

PMID- 29038671
TI  - Inspiratory Muscle Training in the Intensive Care Unit: A New Perspective.
AB  - BACKGROUND: Prolonged use of mechanical ventilation (MV) leads to weakening of
      the respiratory muscles, especially in patients subjected to sedation, but this
      effect seems to be preventable or more quickly reversible using respiratory
      muscle training. The aims of the study were to assess variations in respiratory
      and hemodinamic parameters with electronic inspiratory muscle training (EIMT) in
      tracheostomized patients requiring MV and to compare these variations with those
      in a group of patients subjected to an intermittent nebulization program (INP).
      METHODS: This was a pilot, prospective, randomized study of tracheostomized
      patients requiring MV in one intensive care unit (ICU). Twenty-one patients were
      randomized: 11 into the INP group and 10 into the EIMT group. Two patients were
      excluded in experimental group because of hemodynamic instability. RESULTS: In
      the EIMT group, maximal inspiratory pressure (MIP) after training was
      significantly higher than that before (P = 0.017), there were no hemodynamic
      changes, and the total weaning time was shorter than in the INP group (P =
      0.0192). CONCLUSION: The EIMT device is safe, promotes an increase in MIP, and
      leads to a shorter ventilator weaning time than that seen in patients treated
      using INP.

PMID- 29038672
TI  - Safety Analysis of Autologous Stem Cell Therapy in a Variety of Degenerative
      Diseases and Injuries Using the Stromal Vascular Fraction.
AB  - BACKGROUND: Stem cells from adipose tissue offer a novel therapy for patients
      with damaged tissue. Stromal vascular fraction (SVF) injected into patients may
      reduce inflammation, promote healing, and repair damaged/scarred tissue. SVF can
      be isolated from fat (adipose) tissue in an outpatient procedure. The SVF
      population includes mesenchymal stem cells (MSCs), pericytes,
      endothelial/progenitor cells, fibroblasts and growth factors where the adipocyte
      (fat cell) population has been removed. Here we describe the use of SVF in the
      clinic for degenerative diseases in orthopedics, neurological conditions and
      systemic conditions in 676 patients. METHODS: This study demonstrated the strong
      safety profile from a multi-center analysis of SVF injection in treating various
      diseases. Approximately 60 mL of fat tissue was removed from the abdomen or
      flanks using a local tumescent liposuction procedure. The fat was separated via
      centrifuge to isolate the SVF and the cells were delivered intraarticularly,
      intravenously, intrathecally, or intradiscally directly into the same patient.
      All subjects were monitored for adverse events. RESULTS: The procedure
      demonstrates exceptional patient safety, and the study underscores the safety of
      autologous stem cell therapy in general. Few adverse events were reported and
      were overwhelmingly of mild and transient nature, such as the expected soreness
      at the site of liposuction and occasional headache. CONCLUSION: The three deaths
      reported were most likely not related to the treatment but instead to the
      underlying disease. Our study demonstrates a strong safety profile with low
      complication rates.

PMID- 29038673
TI  - Thiazides and Osteoporotic Spinal Fractures: A Suspected Linkage Investigated by
      Means of a Two-Center, Case-Control Study.
AB  - BACKGROUND: An alleged association of chronic use of thiazide diuretics with an
      increased risk of bone fragility fractures has been highlighted by a relatively
      recent prospective cohort study. However, the concept that thiazides exert a
      beneficial effect on osteoporosis is still a predominant view. This effect would
      be mediated by the decrease in renal clearance of calcium ions, a pharmacological
      feature recognized for a long time now to this class of drugs, as opposed to the
      increase in calcium urinary excretion attributed instead to loop diuretics, i.e.
      furosemide and similar drugs. The purpose of this retrospective study was to
      attempt to clarify whether regular use of thiazide diuretics as antihypertensive
      therapeutics is associated with a significantly increased risk of osteoporotic
      fractures in female patients aged 65 or over. METHODS: In this two-center
      retrospective study, we followed up a cohort of female patients with (n = 80) and
      without (n = 158) thiazide-induced hyponatremia. RESULTS: A total of 48
      osteoporotic fractures were recorded during a median follow-up period of 57.5
      months. By means of univariate regression analysis, an association was found
      between thiazide-induced hyponatremia and increased risk of vertebral fractures
      (odds ratio (OR): 7.6; 95% confidence interval (CI): 3.755 - 15.39; P < 0.0001).
      Multivariate regression analysis, however, showed that age (OR: 1.823; 95% CI:
      1.211 - 2.743) and body mass index (OR: 0.156; 95% CI: 0.038 - 0.645) were the
      only independent predictors of osteoporotic fractures. No association of a
      history of thiazide-induced hyponatremia and risk of fracture was noticeable in
      the final model. CONCLUSIONS: Because thiazide-induced hyponatremia was
      associated with spinal fractures in univariate but not multivariate analysis, a
      possible explanation is that hyponatremia may be a confounder of the relation
      between body mass and spinal fractures. Indeed, reduced body mass especially
      among elderly women with small body build may confer heightened risk of thiazide
      induced hyponatremia because of decreased bone sodium available for exchange with
      the serum sodium. Thus, occurrence of hyponatremia could only serve as an
      indirect surrogate marker for osteoporosis risk.

PMID- 29038674
TI  - Recent Reason for Hindering Medications for Perinatal Mental Disorders in Japan.
AB  - BACKGROUND: We examined the recent reasons for hindering antipsychotic
      medications during pregnancy in Japan. METHODS: We retrospectively analyzed the
      medical charts of all women who gave birth after 22 weeks' gestation at Japanese
      Red Cross Katsushika Maternity Hospital from August 2016 to July 2017. RESULTS:
      Four pregnant women with mental disorders (three schizophrenia and one adjustment
      disorder) kept the interruption of medications under their partners' compulsion.
      All of their partners had a history of mental disorders (two schizophrenia, one
      anxiety disorder and one adjustment disorder). CONCLUSION: In cases of pregnancy
      requiring mental health care, mental health care on partners seemed to be also
      needed.

PMID- 29038675
TI  - Secondary Central Nerve System Lymphoma With Intratumoral Hemorrhage Suggested as
      Intravascular Lymphoma by Autopsy: A Case Report.
AB  - Intravascular large B-cell lymphoma (IVL) is a rare type of extranodal diffuse
      large B-cell lymphoma (DLBCL), which often infiltrates the central nervous system
      (CNS) during the clinical course. Cerebral hemorrhage in patients with CNS
      lymphoma at presentation is rare. Herein, we describe a case of secondary CNS
      lymphoma with intratumoral hemorrhage, which was suggested as IVL from autopsy
      findings. A 76-year-old Japanese man with a history of treatment for B-cell non
      Hodgkin's lymphoma was transferred to our hospital in an ambulance for
      generalized convulsions. Brain CT scan revealed a high-density tumor with edema
      and intratumoral hemorrhage in the left temporal lobes. He died in a rapid
      course, and autopsy revealed a focal hemorrhage with diffuse infiltration of
      lymphoma cells in the left temporal lobe and findings suggestive of IVL.
      Furthermore, the autopsy revealed a discrepancy in the CD20 immunostaining of
      lymphoma cells between the brain and other organs. Clinicians should not
      eliminate CNS lymphoma from the differential diagnosis of intracranial tumor with
      hemorrhage. Although many patients with IVL have rapidly progressive courses, it
      is very important to diagnose IVL at the initial onset, even in serious
      situations, to consider CNS prophylaxis.

PMID- 29038676
TI  - Adult-Onset Henoch-Schonlein Purpura Duodenitis.
AB  - Henoch-Schonlein purpura (HSP) is an immune-mediated vasculitis. HSP presents
      with purple spots on the skin (purpura), arthralgia, digestive problems, and
      kidney injury. HSP is most commonly seen in children, and rarely presents in
      adults. The pathogenesis involves the deposition of immune complexes in small to
      medium size blood vessels which leads to necrosis and inflammation. Most patients
      recover after symptomatic treatment, while more severe cases are treated with
      steroids. We report a 28-year-old female patient who presented with two episodes
      of hematemesis, worsening abdominal pain, and bloody diarrhea. Physical
      examination showed erythematous, palpable, purpuric rashes on her thighs and
      lower legs. Contrast-enhanced computed tomography (CT) scan showed thickening of
      the duodenal wall, and upper endoscopy revealed mild gastric erythema and diffuse
      erythematous, hemorrhagic, friable mucosa with superficial, thick, adherent white
      exudate seen in the second portion of the duodenum, consistent with the diagnosis
      of HSP. We report on the clinical presentation of our patient, and review adult
      onset HSP.

PMID- 29038677
TI  - Newly Diagnosed Idiopathic Liver Abscess: Colonoscopy Required!
AB  - Liver abscess is the most common type of visceral abscess reported in the United
      States. Biliary tract disease is the most common cause of the development of
      liver abscess. In the last decade, many cases of liver abscesses silently
      manifesting as colon cancer have been reported in East Asian countries. We herein
      describe a case of an immunocompetent man who immigrated from East Africa to
      Unites States and presented with a suspicion of colon mass with metastasis to the
      liver, and who was later diagnosed to have a colonic malignancy with a
      concomitant liver abscess. Our aim was to make clinicians aware of the importance
      of ruling out occult colonic malignancy in patients with idiopathic liver
      abscess.

PMID- 29038678
TI  - Posttraumatic growth and recovery from addiction.
AB  - Background: It is well documented that individuals coping with adverse events
      report both negative outcomes, such as posttraumatic stress symptoms, as well as
      positive changes, described as posttraumatic growth. Positive changes are also
      reported in people who have recovered from substance abuse. It seems plausible
      from the literature that both of these types of positive changes have elements in
      common. To date, no published studies have examined positive outcomes among
      people who have recovered from addiction. Objectives: In this study,
      posttraumatic growth in individuals who were formerly addicted to alcohol or
      substances, termed 'addiction-related growth,' was examined. Addiction-related
      growth refers to the growth that an individual undergoes as a result of the
      addiction itself, and the recovery from the addiction. A successful recovery from
      addiction is associated with positive changes, particularly regarding
      spirituality and meaning-making, and the construct of addiction-related growth
      may explain why. Method: This cross-sectional study examined growth among 104
      individuals who had recovered from addiction who were recruited from addiction
      treatment programmes, between February and July 2012. Questionnaires assessed
      demographics and substance abuse use and treatment, posttraumatic growth (PTGI);
      social support (Perceived Social Support Questionnaire); and help-seeking
      (Willingness to Seek Help Scale). Data was analysed using an analysis of variance
      (ANOVA), Pearson correlations, and multiple regression. Results: Results
      indicated that addiction-related growth is a phenomenon that accurately captures
      the positive changes experienced as a result of an individual's struggle with
      addiction and recovery. This growth was found to be associated with participation
      in 12-steps programmes, and to be predicted by levels of perceived social
      support. Conclusions: The results show that recovery from addiction is associated
      with addiction-related growth. These positive changes, along with the importance
      of communal social support, resemble the changes that take place as a result of
      processes described in 12-steps programmes.

PMID- 29038679
TI  - Day patient treatment for traumatic grief: preliminary evaluation of a one-year
      treatment programme for patients with multiple and traumatic losses.
AB  - Background: Bereaved individuals who have lost a loved one under traumatic
      circumstances can develop symptoms of Persistent Complex Bereavement Disorder
      (PCBD) and/or Posttraumatic Stress Disorder (PTSD). This is particularly common
      in refugees, as they frequently have been confronted with multiple traumatic
      losses. For patients with severe PTSD and traumatic grief a treatment programme
      was developed, embedding individual traumatic grief focused therapy in a group
      based multidisciplinary day patient treatment programme. The day patient
      treatment comprised a weekly five-hour programme consisting of three phases with
      a duration of four months each. Objective: To evaluate the feasibility and
      potential effectiveness of the treatment programme. Method: Data were analyzed
      from 16 participants treated between October 2013 and March 2014. PTSD severity
      and PTSD/PCBD diagnoses were measured during the initial and final phases of
      treatment using the Clinician-Administered PTSD Scale for DSM-IV (CAPS) and the
      Traumatic Grief Inventory Self Report (TGI-SR). One clinical case is presented in
      more detail. Treatment attendance was also registered and therapist satisfaction
      was evaluated in a focus group. Results: Thirteen patients (81%) completed the
      treatment. Each day of the treatment programme was attended by a mean of 76% of
      the participants. In the focus group, therapists noted symptom reduction in their
      patients and they therefore regarded Brief Eclectic Psychotherapy for Traumatic
      Grief (BEP-TG) as an effective therapy for their patients. During treatment,
      significant decreases in PTSD severity as well as diagnosable PTSD and PCBD were
      observed. Conclusions: Results support the feasibility and potential
      effectiveness of the day patient treatment programme for traumatic grief. The
      programme appears to be particularly suitable for refugees with severe PTSD and
      PCBD psychopathology, who may not benefit enough from usual care.

PMID- 29038680
TI  - Post-traumatic stress disorder moderates the relationship between trauma exposure
      and chronic pain.
AB  - Background: Trauma exposure and post-traumatic stress disorder (PTSD) are risk
      factors for chronic pain. Objective: This study investigated how exposure to
      intentional and non-intentional traumatic events and PTSD are related to pain
      severity and outcome of treatment in chronic pain patients. Methods: We assessed
      exposure to potentially traumatizing events, psychiatric diagnosis with
      structured clinical interview, and pain severity in 63 patients at a secondary
      multidisciplinary pain clinic at the beginning of treatment, and assessed level
      of pain at follow up. Exposure to potentially traumatizing events and PTSD were
      regressed on pain severity at the initial session and at follow up in a set of
      multiple regression analysis. Results: The participants reported exposure to an
      average of four potentially traumatizing events, and 32% had PTSD. Exposure to
      intentional traumatic events and PTSD were significantly associated with more
      severe pain, and PTSD significantly moderated the relationship between trauma
      exposure and pain (all p < .05). The treatment programme reduced pain moderately,
      an effect that was unrelated to trauma exposure and PTSD. Conclusions: Trauma
      exposure is related to chronic pain in the same pattern as to mental disorders,
      with intentional trauma being most strongly related to pain severity. PTSD
      moderated the relationship between trauma exposure and pain. While pain patients
      with PTSD initially report more pain, they responded equally to specialist pain
      treatment as persons without PTSD.

PMID- 29038681
TI  - Treatment of dissociative disorders and reported changes in inpatient and
      outpatient cost estimates.
AB  - Background: Interpersonal trauma and trauma-related disorders cost society
      billions of dollars each year. Because of chronic and severe trauma histories,
      dissociative disorder (DD) patients spend many years in the mental health system,
      yet there is limited knowledge about the economic burden associated with DDs.
      Objective: The current study sought to determine how receiving specialized
      treatment would relate to estimated costs of inpatient and outpatient mental
      health services. Method: Patients' and individual therapists' reports of
      inpatient hospitalization days and outpatient treatment sessions were converted
      into US dollars. DD patients and their clinicians reported on use of inpatient
      and outpatient services four times over 30 months as part of a larger,
      naturalistic, international DD treatment study. The baseline sample included 292
      clinicians and 280 patients; at the 30-month follow-up, 135 clinicians and 111
      patients. Missing data were replaced in analyses to maintain adequate statistical
      power. The substantial attrition rate (>50%) should be considered in interpreting
      findings. Results: Longitudinal and cross-sectional analyses of cost estimates
      based on patient reported inpatient hospitalization significantly decreased over
      time. Longitudinal cost estimates based on clinician-reported outpatient services
      also significantly decreased over time. Cross-sectional cost estimates based on
      patient and clinician reported inpatient hospitalization were significantly lower
      for patients in later stages of treatment compared to those struggling with
      safety and stabilization. Cross-sectional cost estimates based on clinician
      reported outpatient services were significantly lower for patients in later
      stages of treatment compared to those in early stages. Conclusions: This pattern
      of longitudinal and cross-sectional reductions in inpatient and outpatient costs,
      as reported by both patients and therapists, suggests that DD treatment may be
      associated with reduced inpatient and outpatient costs over time. Although these
      preliminary results show decreased mental health care utilization and associated
      estimated costs, it is not clear whether it was treatment that caused these
      important changes.

PMID- 29038682
TI  - Depression as a moderator of STAIR Narrative Therapy for women with post
      traumatic stress disorder related to childhood abuse.
AB  - Background: Depression among those who have experienced childhood abuse is
      associated with earlier onset, more persistent and severe symptoms, more frequent
      relapse, and poorer treatment outcomes across a variety of psychiatric disorders.
      In addition, individuals with a history of childhood abuse are more likely to
      develop post-traumatic stress disorder (PTSD) co-occurring with depression.
      Objective: This study evaluated whether severity of depression moderated the
      outcome in a PTSD treatment for childhood abuse survivors. Specifically, we
      assessed whether individuals with significant depression obtained better outcomes
      when provided with a two-module treatment which included a skills training
      component with behavioral activation interventions, Skills Training in Affective
      and Interpersonal Regulation (STAIR) followed by a trauma-focused component,
      Narrative Therapy, as compared to two control conditions where one component
      (STAIR or Narrative Therapy) was replaced with Supportive Counseling. Method:
      Participants were 104 women with PTSD related to childhood abuse. Participants
      were randomized into three conditions: (1) STAIR plus Narrative Therapy (SNT),
      (2) STAIR plus Supportive Counseling (SSC), and (3) Supportive Counseling plus
      Narrative Therapy (SCNT). Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV)
      PTSD symptom severity was assessed at pre-treatment, post-treatment, and 3 and 6
      month follow-up. Results: Participants with severe depression showed superior
      PTSD symptom reduction following SNT, while those in the other two conditions
      experienced a loss of improvement after treatment ended. A similar finding was
      obtained among those with moderate depression, while among those with low levels
      of depression, outcomes did not differ across the three treatment conditions.
      Conclusions: Childhood abuse survivors with severe depression obtained superior
      outcomes in a treatment that combined skills training with trauma-focused work.
      Skills packages which contain behavioral activation interventions in combination
      with trauma-focused work may be particularly beneficial for patients with
      childhood abuse and severe depression.

PMID- 29038683
TI  - Bayesian hypothesis testing for human threat conditioning research: an
      introduction and the condir R package.
AB  - Threat conditioning procedures have allowed the experimental investigation of the
      pathogenesis of Post-Traumatic Stress Disorder. The findings of these procedures
      have also provided stable foundations for the development of relevant
      intervention programs (e.g. exposure therapy). Statistical inference of threat
      conditioning procedures is commonly based on p-values and Null Hypothesis
      Significance Testing (NHST). Nowadays, however, there is a growing concern about
      this statistical approach, as many scientists point to the various limitations of
      p-values and NHST. As an alternative, the use of Bayes factors and Bayesian
      hypothesis testing has been suggested. In this article, we apply this statistical
      approach to threat conditioning data. In order to enable the easy computation of
      Bayes factors for threat conditioning data we present a new R package named
      condir, which can be used either via the R console or via a Shiny application.
      This article provides both a non-technical introduction to Bayesian analysis for
      researchers using the threat conditioning paradigm, and the necessary tools for
      computing Bayes factors easily.

PMID- 29038684
TI  - Modification of episodic memories by novel learning: a failed replication study.
AB  - Background: After reactivation, memories can become unstable and sensitive to
      modification before they are restored into long-term memory. Using behavioural
      manipulations, reactivated memories may be disrupted via the mechanism of
      interference (i.e. novel learning). In a laboratory study, Wichert et al. (2013a)
      showed that new learning after reactivation changed episodic memory, while new
      learning alone or reactivation alone did not. Objective: Given the potential
      clinical application of such a procedure in trauma-focused psychological
      treatments, such as CBT or EMDR, the aim of this study was to replicate Wichert
      et al. Method: On Day 1, participants (N = 96) viewed and recalled a series of
      emotional and non-emotional pictures. Then, participants were randomized to one
      of four groups. One week later, on Day 8, Group 1 reactivated the previously
      learned pictures and learned new pictures. To control for specific effects of
      reactivation or new learning, Group 2 only reactivated the previously learned
      pictures, and Group 3 only learned new pictures. Group 4 received no reactivation
      and no new learning. On Day 9, all groups indicated for each picture out of a
      series whether they had seen it on Day 1. Results: The data were analysed using
      Bayesian hypothesis testing, which allows for quantifying the evidence in favour
      of the alternative and the null hypothesis. In general, results showed that Group
      1 recognized fewer pictures from Day 1 compared to Groups 2 and 4 on Day 9.
      However, the expected difference between new learning following reactivation
      (i.e. Group 1) and new learning alone (i.e. Group 3) was not substantially
      supported by the data for any of our dependent measures. Conclusions: We
      replicated some of the findings by Wichert et al., but did not find substantial
      support for the critical difference between new learning following reactivation
      and new learning alone.

PMID- 29038685
TI  - Exploring expectation effects in EMDR: does prior treatment knowledge affect the
      degrading effects of eye movements on memories?
AB  - Background: Eye movement desensitization and reprocessing (EMDR) is an effective
      psychological treatment for posttraumatic stress disorder. Recalling a memory
      while simultaneously making eye movements (EM) decreases a memory's vividness
      and/or emotionality. It has been argued that non-specific factors, such as
      treatment expectancy and experimental demand, may contribute to the EMDR's
      effectiveness. Objective: The present study was designed to test whether
      expectations about the working mechanism of EMDR would alter the memory
      attenuating effects of EM. Two experiments were conducted. In Experiment 1, we
      examined the effects of pre-existing (non-manipulated) knowledge of EMDR in
      participants with and without prior knowledge. In Experiment 2, we experimentally
      manipulated prior knowledge by providing participants without prior knowledge
      with correct or incorrect information about EMDR's working mechanism. Method:
      Participants in both experiments recalled two aversive, autobiographical memories
      during brief sets of EM (Recall+EM) or keeping eyes stationary (Recall Only).
      Before and after the intervention, participants scored their memories on
      vividness and emotionality. A Bayesian approach was used to compare two competing
      hypotheses on the effects of (existing/given) prior knowledge: (1) Prior
      (correct) knowledge increases the effects of Recall+EM vs. Recall Only, vs. (2)
      prior knowledge does not affect the effects of Recall+EM. Results: Recall+EM
      caused greater reductions in memory vividness and emotionality than Recall Only
      in all groups, including the incorrect information group. In Experiment 1, both
      hypotheses were supported by the data: prior knowledge boosted the effects of EM,
      but only modestly. In Experiment 2, the second hypothesis was clearly supported
      over the first: providing knowledge of the underlying mechanism of EMDR did not
      alter the effects of EM. Conclusions: Recall+EM appears to be quite robust
      against the effects of prior expectations. As Recall+EM is the core component of
      EMDR, expectancy effects probably contribute little to the effectiveness of EMDR
      treatment.

PMID- 29038686
TI  - The assessment of psychopathology among traumatized refugees: measurement
      invariance of the Harvard Trauma Questionnaire and the Hopkins Symptom Checklist
      25 across five linguistic groups.
AB  - Background: Questionnaires are widely used to assess the mental health status of
      refugees, whereas their construct validity largely remains unexplored. Objective:
      This study examined the construct validity of two widely-used instruments for the
      assessment of PTSD symptoms (Harvard Trauma Questionnaire [HTQ]; 16 items) and
      symptoms of anxiety and depression (Hopkins Symptom Check list-25 [HSCL-25]; 25
      items) among Dutch and refugee patients with different linguistic backgrounds.
      Method: We applied exploratory factor analyses and measurement invariance
      analyses to test construct validity.Participants (n =1 256) were divided into
      five linguistic groups defined by language family, including four non-western
      linguistic groups (Indo-Iranian [n = 262], Niger-Congo [n = 134], Semitic [n =
      288], and South Slavic languages [n = 199]) and one western linguistic group
      (Germanic languages; Dutch [n = 373]). Results: Exploratory factor analysis
      yielded a 3-factor structure of the HTQ and a 2-factor structure of the HSCL-25.
      Measurement invariance 20 analyses on the HTQ showed strong measurement
      invariance across the groups of refugee patients. However, Dutch patients
      reported milder symptom severity on most items of the HTQ. Measurement invariance
      analyses on the HSCL-25 (not conducted in Dutch patients) indicated partial
      strong measurement invariance across refugee patients. Conclusion: We conclude
      that mental health constructs measured by the HTQ and the HSCL25 25 are to a
      large extent interpreted in a similar way by refugee patients. This indicates
      that these instruments can be applied in non-western refugee patient populations,
      and that local idioms of distress and inherent response patterns may not play a
      major role when applying the HTQ and the HSCL-25 in these populations. Yet,
      whereas meaningful comparisons of observed PTSD and depression scores between
      groups of refugee patients with different non30 western linguistic background are
      feasible, comparisons between patients with a western and non-western linguistic
      background, as well as comparisons of anxiety scores, are likely to be biased.
      Future studies need to establish whether the commonly used cut-off scores of both
      questionnaires apply for refugee patients with non-western linguistic
      backgrounds.

PMID- 29038687
TI  - Mental health status of North Korean refugees in South Korea and risk and
      protective factors: a 10-year review of the literature.
AB  - Background: North Korean refugees (NKRs) are often exposed to traumatic events in
      North Korea and during their defection. Furthermore, they face sociocultural
      barriers in adapting to the new society to which they have defected. Objective:
      To integrate previous findings on this mentally vulnerable population, we
      systematically reviewed articles on the mental health of NKRs in South Korea.
      Method: We searched for empirical studies conducted in the last 10 years in six
      online databases (international journals: Embase, PubMed, Scopus, Web of Science;
      Korean journals: DBPIA, KMbase) through June 2017. Only quantitative studies
      using new empirical data on the mental health of NKRs were included. We
      summarized the 56 studies ultimately selected in terms of NKRs' mental health
      status and three domains of associated factors: pre- and post-settlement factors
      and personal factors. Results: NKRs had a high prevalence and severity of
      psychiatric symptoms, particularly post-traumatic stress disorder and depression.
      We identified nine risk factors consistently found in previous studies, including
      traumatic experience, longer stay periods in third country, forced repatriation,
      acculturative stress, low income, older age, poor physical health, and female and
      male sex, as well as four protective factors, including educational level in
      North Korea, social support, family relationship quality, and resilience.
      Conclusions: We suggest that future studies focus on the causal interactions
      between different risk and protective factors and mental health outcomes among
      NKRs from a longitudinal perspective. Furthermore, comprehensive policies for
      NKRs' psychological adaptation are needed, particularly the development of
      evidence-based mental health interventions.

PMID- 29038688
TI  - Symptoms of posttraumatic stress disorder in a clinical sample of refugees: a
      network analysis.
AB  - Background: Network analysis is an emerging methodology for investigating
      psychopathological symptoms. Given the unprecedented number of refugees and the
      increased prevalence of mental disorders such as posttraumatic stress disorder
      (PTSD) in this population, new methodologies that help us better to understand
      psychopathology in refugees are crucial. Objective: The objective of this study
      was to explore the network structure and centrality indices of DSM-5 PTSD
      symptoms in a cross-sectional clinical sample of 151 severely traumatized
      refugees with and without a formal PTSD diagnosis. Method: The R-packages qgraph
      and bootnet were used to estimate the structure of a PTSD symptom network and its
      centrality indices. In addition, robustness and significance analyses for the
      edges weights and the order of centrality were performed. Results: Three pairs of
      symptoms showed significantly stronger connections than at least half of the
      other connections: hypervigilance and exaggerated startle response, intrusion and
      difficulties falling asleep, and irritability or outbursts of anger and self
      destructive or reckless behaviour. Emotional cue reactivity had the highest
      centrality and trauma-related amnesia the lowest. Conclusion: Although only 51.0%
      of participants fulfilled criteria for a probable PTSD diagnosis, emotional cue
      reactivity showed the highest centrality, emphasizing the importance of emotional
      trauma reminders in severely traumatized refugees attending an outpatient clinic.
      However, due to the small sample size, the results should be interpreted with
      care.

PMID- 29038689
TI  - Making connections: exploring the centrality of posttraumatic stress symptoms and
      covariates after a terrorist attack.
AB  - Background: Posttraumatic stress symptoms are interconnected. Knowledge about
      which symptoms of posttraumatic stress are more strongly interconnected or
      central than others may have implications for the targeting of clinical
      interventions. Exploring whether symptoms of posttraumatic stress may be
      differentially related to covariates can contribute to our knowledge on how
      posttraumatic stress symptoms arise and are maintained. Objective: This study
      aimed to identify the most central symptoms of posttraumatic stress and their
      interconnections, and to explore how covariates such as exposure, sex,
      neuroticism, and social support are related to the network of symptoms of
      posttraumatic stress. Method: This study used survey data from ministerial
      employees collected approximately 10 months after the 2011 Oslo bombing that
      targeted the governmental quarters (n = 190). We conducted network analyses using
      Gaussian graphical models and the lasso regularization. Results: The network
      analysis revealed reliably strong connections between intrusive thoughts and
      nightmares, feeling easily startled and overly alert, and between feeling
      detached and emotionally numb. The most central symptom in the symptom network
      was feeling emotionally numb. The covariates were generally not found to have
      high centrality in the symptom network. An exception was that being female was
      connected to a high physiological reactivity to reminders of the trauma.
      Conclusions: Ten months after a workplace terror attack emotional numbness
      appears to be of high centrality in the symptom network of posttraumatic stress.
      Fear circuitry and dysphoric symptoms may constitute two functional entities in
      chronic posttraumatic stress. Clinical interventions targeting numbness may be
      beneficial in the treatment of posttraumatic stress, at least after workplace
      terrorism.

PMID- 29038690
TI  - A Bayesian network analysis of posttraumatic stress disorder symptoms in adults
      reporting childhood sexual abuse.
AB  - Background: The network approach to mental disorders offers a novel framework for
      conceptualizing posttraumatic stress disorder (PTSD) as a causal system of
      interacting symptoms. Objective: In this study, we extended this work by
      estimating the structure of relations among PTSD symptoms in adults reporting
      personal histories of childhood sexual abuse (CSA; N = 179).   Method: We
      employed two complementary methods. First, using the graphical LASSO, we computed
      a sparse, regularized partial correlation network revealing associations (edges)
      between pairs of PTSD symptoms (nodes). Next, using a Bayesian approach, we
      computed a directed acyclic graph (DAG) to estimate a directed, potentially
      causal model of the relations among symptoms. Results: For the first network, we
      found that physiological reactivity to reminders of trauma, dreams about the
      trauma, and lost of interest in previously enjoyed activities were highly central
      nodes. However, stability analyses suggest that these findings were unstable
      across subsets of our sample. The DAG suggests that becoming physiologically
      reactive and upset in response to reminders of the trauma may be key drivers of
      other symptoms in adult survivors of CSA. Conclusions: Our study illustrates the
      strengths and limitations of these network analytic approaches to PTSD.

PMID- 29038692
TI  - Psychotraumatology in Greece.

PMID- 29038691
TI  - A network analysis of anger, shame, proposed ICD-11 post-traumatic stress
      disorder, and different types of childhood trauma in foster care settings in a
      sample of adult survivors.
AB  - Background: Anger and shame are aspects that are specifically associated with
      psychopathology and maladaptation after childhood abuse and neglect. They are
      known to influence symptom maintenance and exacerbation; however, their
      interaction is not fully understood. Objective: To explore with network analysis
      the association and interaction of prolonged, complex interpersonal childhood
      abuse and neglect in institutional foster care settings [institutional abuse
      (IA)] with anger, shame, and the proposed 11th revision of the International
      Statistical Classification of Diseases and Related Health Problems (ICD-11) post
      traumatic stress disorder (PTSD) symptoms in adult survivors. Method: Adult
      survivors of IA (N = 220, mean age = 57.95 years) participated in the study and
      were interviewed using the Childhood Trauma Questionnaire, the International
      Trauma Questionnaire, the State-Trait Anger Expression Inventory, the Displaced
      Aggression Questionnaire, and shame-related items. To identify the most central
      aspects, we used a staged network analysis and centrality analysis approach: (1)
      on the scale level; (2) on the item/symptom level; and (3) with modularity
      analysis to find communities within the item-level network. Results: Trait anger,
      anger rumination, emotional abuse, and PTSD re-experiencing symptoms played the
      most important roles on a scale level and were then further analyzed on the
      item/symptom level. The most central symptom on the item level was anger
      rumination related to meaningful past events. The modularity analysis supported
      discriminant validity of the included scales. Conclusions: Anger is an important
      factor in the psychopathological processes following childhood abuse. Anger
      rumination is closely related to PTSD symptoms; however, anger is not a part of
      the proposed ICD-11 PTSD in the present study.

PMID- 29038693
TI  - Bio-psycho-social factors affecting sexual self-concept: A systematic review.
AB  - BACKGROUND: Nowadays, it is believed that mental and emotional aspects of sexual
      well-being are the important aspects of sexual health. Sexual self-concept is a
      major component of sexual health and the core of sexuality. It is defined as the
      cognitive perspective concerning the sexual aspects of 'self' and refers to the
      individual's self-perception as a sexual creature. OBJECTIVE: The aim of this
      study was to assess the different factors affecting sexual self-concept. METHODS:
      English electronic databases including PubMed, Scopus, Web of Science and Google
      Scholar as well as two Iranian databases including Scientific Information
      Database and Iranmedex were searched for English and Persian-language articles
      published between 1996 and 2016. Of 281 retrieved articles, 37 articles were
      finally included for writing this review article. RESULTS: Factors affecting
      sexual self-concept were categorized to biological, psychological and social
      factors. In the category of biological factors, age gender, marital status, race,
      disability and sexual transmitted infections are described. In the psychological
      category, the impact of body image, sexual abuse in childhood and mental health
      history are present. Lastly, in the social category, the roles of parents, peers
      and the media are discussed. CONCLUSION: As the development of sexual self
      concept is influenced by multiple events in individuals' lives, to promotion of
      sexual self-concept, an integrated implementation of health policies is
      recommended.

PMID- 29038694
TI  - Dietary habits, physical activity and diabetes perception among patients with
      type 2 diabetes mellitus in Tabuk City, Saudi Arabia.
AB  - BACKGROUND: Medical nutritional therapy is an important aspect of diabetes care,
      there is an increasing awareness of breakfast skipping, late dinner and meal
      contents on diabetes control. AIM: To assess dietary habits, physical activity
      and diabetes perception among patients with type 2 diabetes. METHODS: This case
      control study was conducted among patients with diabetes mellitus at the diabetes
      center in Tabuk City, Saudi Arabia during the period from March through June
      2017. One hundred patients with type 2 diabetes and 150 control subjects were
      interviewed to collect demographic data regarding, breakfast skipping, late
      dinner intake, and fruit, vegetables, sweet food, and fast food consumption.
      Diabetic patients' perception of their disease was also assessed. (If diabetes is
      serious, it can be prevented and reversible). Data were analyzed by SPSS version
      20 using Chi-square and independent-samples t-test. RESULTS: In the present
      study, body mass index (BMI) (p<0.001), fast food consumption (p<0.001), fruit
      consumption (p=0.004), and breakfast skipping (p<0.001) were higher among
      patients with diabetes compared to controls. No differences were found regarding
      the level of exercise, smoking, late dinner intake and diabetes perception. A
      significant statistical difference was observed between poor and accepted control
      regarding sweet food intake (p=0.046) and exercise (p=0.017). CONCLUSION:
      Patients with type 2 diabetes had higher BMI, and were more likely to skip
      breakfast, consume less fast food and more fruits than control subjects. More
      physical activity and less sweet food consumption was observed among patients
      with accepted glycemic control.

PMID- 29038695
TI  - Deep venous thrombosis among diabetic patients in King Abdulaziz University (KAU)
      Hospital, Jeddah, Kingdom of Saudi Arabia.
AB  - BACKGROUND: Deep venous thrombosis (DVT) is a major cause of morbidity and
      mortality among hospitalized patients worldwide and, simultaneously, the most
      preventable. Studies revealed several risk factors of deep venous thrombosis in
      hospitalized patients. OBJECTIVE: to identify frequency and factors associated
      with occurrence of deep venous thrombosis among diabetic patients referred to
      King Abdulaziz University (KAU) Hospital, Jeddah, Kingdom of Saudi Arabia.
      METHODS: This cross-sectional hospital-based study was conducted from June to
      December, 2016. All diabetic patients referred to the hospital departments and
      who were suspected to have deep venous thrombosis (DVT) and subjected to Doppler
      examination were included in the study. A questionnaire was designed to obtain
      data about deep venous thrombosis frequency among participants and factors
      associated with the development of deep venous thrombosis among them. Data was
      collected through face to face interviews with patients included in the study. We
      used SPSS version 16 for data analysis through descriptive statistics and Chi
      square test. RESULTS: DVT was detected in 14.7 % of the examined patients. There
      were significant and positive associations between age and DVT (X2=10.13, p=0.03)
      and between ischemic heart disease and DVT (X2=1.628, p=0.043) with the
      development of deep venous thrombosis among the studied patients. On the other
      hand, gender, other comorbidities, history of previous DVT, being bed ridden and
      using orthopedic casting were not significantly associated with the occurrence of
      deep venous thrombosis among the participants. CONCLUSION: DVT development rate
      among the participants was 14.7 %. Aging was significantly associated with DVT
      occurrence. Most of the studied factors and comorbidities had no significant role
      in DVT development among participants and only ischemic heart disease was
      significantly associated with DVT development.

PMID- 29038696
TI  - Exploring the perception of nursing students about consequences of reflection in
      clinical settings.
AB  - BACKGROUND: Reflection on practical experiences is a key element that enables
      students to recognize their own strengths and weaknesses and develop nursing
      skills. Whilst reflection may enhance students' learning in practice, there is
      little evidence about nursing students' perception of the consequences of
      reflection in clinical settings. OBJECTIVE: This study aimed to explore Iranian
      nursing students' perception regarding the consequences of reflection during
      clinical practices. METHODS: This qualitative study was conducted by a
      conventional content analysis approach in two nursing schools at Shiraz and Fasa
      Universities of Medical Sciences in Iran. Data were collected through in-depth
      semi-structured interviews during 2015-2016, from 20 students selected by
      purposive sampling. All the interviews were tape-recorded, transcribed verbatim,
      and analyzed by content analysis method. Rigor of this study was approved by
      member check and external audit. RESULTS: Two categories emerged from the data
      analysis, including movement toward professionalism and self-actualization of
      emotions. The former consisted of three subcategories of function modification,
      sharing experiences and generalizing experiences. The latter consisted of two
      subcategories of inner satisfaction and peace of mind. CONCLUSION: The results
      indicated that nursing students' reflection in clinical settings is effective in
      personal and professional levels. Reflection in a personal level led to positive
      emotions that increased the quality of care in patients. Accordingly, nursing
      educators need to create a nurturing climate as well as supporting reflective
      behaviors of nursing students.

PMID- 29038697
TI  - The pedagogical effect of a health education application for deaf and hard of
      hearing students in elementary schools.
AB  - BACKGROUND: Deaf or hard-of-hearing children experience difficulties in learning
      health principles. But technology has significantly improved their ability to
      learn. The challenge in e-learning is to design attractive applications while
      having an educational aspect. OBJECTIVE: The aims of this study were to determine
      the pedagogical effectiveness of a health education application for deaf and hard
      of hearing students in elementary schools, and to investigate the student's
      perceptions in different educational grades about the educational effectiveness
      of the text, graphics, video clips, and animation in the application. METHODS:
      The study design was quasi experimental and was conducted in Mashhad in 2016.
      Study population were deaf or hard-of-hearing students in elementary schools. The
      intervention included health application training to deaf and hard-of-hearing
      students in Mashhad. A questionnaire was used for data gathering. The pedagogical
      effectiveness was determined by measuring the modified Adapted Pedagogical Index.
      This index was created based on the characteristics of the application and study
      population. Statistical analysis was performed using the Kruskal-Wallis and Mann
      Whitney tests with Bonferroni adjustment by SPSS 22. RESULTS: Eighty-two students
      participated in the intervention. The value of modified Adapted Pedagogical Index
      was 0.669, indicating that the application was effective. The results of Kruskal
      Wallis H and Mann-Whitney U test showed significant differences in different
      educational grades. (p<0.008). CONCLUSION: Using information technology can
      improve the education of deaf and hard-of-hearing students. Modified Adapted
      Pedagogical Index can be used for evaluation of non-interactive applications for
      elementary school children who are deaf or hard of hearing.

PMID- 29038699
TI  - The correlation of social support with mental health: A meta-analysis.
AB  - BACKGROUND AND AIM: Social support is an important factor that can affect mental
      health. In recent decades, many studies have been done on the impact of social
      support on mental health. The purpose of the present study is to investigate the
      effect size of the relationship between social support and mental health in
      studies in Iran. METHODS: This meta-analysis was carried out in studies that were
      performed from 1996 through 2015. Databases included SID and Magiran, the
      comprehensive portal of human sciences, Noor specialized magazine databases,
      IRANDOC, Proquest, PubMed, Scopus, ERIC, Iranmedex and Google Scholar. The
      keywords used to search these websites included "mental health or general
      health," and "Iran" and "social support." In total, 64 studies had inclusion
      criteria meta-analysis. In order to collect data used from a meta-analysis
      worksheet that was made by the researcher and for data analysis software, CMA-2
      was used. RESULTS: The mean of effect size of the 64 studies in the fixed-effect
      model and random-effect model was obtained respectively as 0.356 and 0.330, which
      indicated the moderate effect size of social support on mental health. The
      studies did not have publication bias, and enjoyed a heterogeneous effect size.
      The target population and social support questionnaire were moderator variables,
      but sex, sampling method, and mental health questionnaire were not moderator
      variables. CONCLUSION: Regarding relatively high effect size of the correlation
      between social support and mental health, it is necessary to predispose higher
      social support, especially for women, the elderly, patients, workers, and
      students.

PMID- 29038698
TI  - Association of hematological indices with prediabetes: A cross-sectional study.
AB  - BACKGROUND: Prediabetes is a condition that occurs when blood glucose levels are
      higher than normal, but not high enough to be classified as diabetes. Prediabetic
      people have an increased risk of developing type 2 diabetes and cardiovascular
      disease. Moreover Hyperglycemia has multiple effects on the hematological
      parameters. OBJECTIVE: To examine the association between hematological indices
      and anthropometric measurement, with prediabetes. METHODS: This cross-sectional
      study was conducted on 125 diabetics and 259 prediabetics in the 20-70 age range.
      They were selected by a convenience sampling method at the Taban Diabetes Center
      in 2015. An oral glucose tolerance test was performed for each participant who
      had never been diagnosed with diabetes. Participants were characterized as having
      prediabetes or diabetes according to American Diabetes Association criteria. The
      hematologic parameters were measured by using Sysmex-KX 21N analyzers. Data were
      analyzed by IBM-SPSS version 22 using independent-samples t-test, Mann-Whitney U
      test, and Pearson's correlation coefficient at p<0.05. RESULTS: There was
      significant difference in mean corpuscular hemoglobin concentration (MCVH)
      (33.81+/-0.92 g/dL vs. 34.06+/-1.05 g/dL) between prediabetes patients and
      diabetes. There was not a statistically significant difference in the
      prediabetics' hematological parameters, compared with the diabetics. In the
      prediabetic group, only the mean corpuscular hemoglobin concentration was found
      to be negatively correlated with diastolic blood pressure (p=0.013) and FBS
      (p=0.026). CONCLUSION: Hematological indices are important markers for the
      assessment of variations in size, number, and maturity of different blood cells.
      Hematological indices could be utile indicators of vascular complication and
      glycemic control in type 2 DM patients. Thus, they are important for the
      evaluation and early management of patients with per diabetes.

PMID- 29038700
TI  - The clinical evaluation of Vi-one chlorhexidine mouthwash on plaque-induced
      gingivitis: A double-blind randomized clinical trial.
AB  - BACKGROUND: Chlorhexidine (CHX) is the most effective antiseptic mouthwash to
      date. Essential oil such as thymol, have inhibitory and biocidal effects a range
      of bacteria. OBJECTIVE: To determine the effect of mouthwash containing CHX and
      thymol on plaque induced gingivitis. METHODS: This double-blind randomized
      clinical trial study was performed on 60 patients with plaque induced gingivitis
      who were randomly divided into two groups: Group I (CHX/thymol mouthwash-Vi-one)
      and Group II (CHX mouthwash-Behsa). Patients in each group underwent scaling and
      root planning and polishing, then were educated about BASS-Method brushing, and
      were recommended Oral-B toothbrushes and Pooneh toothpaste. The two groups were
      asked to rinse their mouths for 60 seconds twice a day, once in the morning and
      once at night, after brushing their teeth. Plaque index, gingival index, bleeding
      index and stain index were evaluated at baseline and 14 days later in Ramfjord
      teeth. Data analysis was conducted using SPSS version 21. Independent-samples t
      test and paired-samples t-test were used for data analysis. RESULTS: The results
      showed that plaque index and gingival index significantly reduced in two groups
      (p<0.001). However, group I was significantly more efficient than group II
      (p<0.001, p=0.021 respectively). Similar results were observed in terms of
      bleeding index with the difference that the two groups did not differ
      significantly from each other (p=0.879). Both groups significantly increased the
      stain index. No remarkable difference was also observed between the two groups
      (p=0.754). CONCLUSION: Based on the results of this study, we can conclude that
      the CHX/thymol mouthwash can be offered to patients with dental plaque-induced
      gingivitis, because it appears to be more effective in controlling dental plaque
      and gingivitis. TRIAL REGISTRATION: The trial was registered at the Iranian
      Registry of Clinical Trials (http://www.irct.ir) with the Irct ID:
      IRCT201602231760N45. FUNDING: This study was part of a thesis and research
      project (Grant No: 9440921) supported and funded by Babol University of Medical
      Sciences. The authors received no financial support from Behsa pharmaceutical
      company (Behsa mouthwash manufacturer) or Rojin cosmetic laboratory (Vi-one
      mouthwash manufacturer) for this study.

PMID- 29038701
TI  - Effect of periodic sildenafil dosage on intraocular pressure in patients with
      erectile dysfunction.
AB  - BACKGROUND AND AIM: Sildenafil is used to treat erectile dysfunction but it has
      association with some side effects. This study was conducted with the aim of
      investigating the effect of duration of taking sildenafil on intraocular pressure
      (IOP) in patients with erectile dysfunction. METHODS: The study population of
      this cross-sectional study were all males with erectile dysfunction referring to
      the urology clinic affiliated to Rafsanjan University of Medical Sciences
      (Kerman, Iran) over a one-year period (2015-2016) among whom 110 patients were
      included in the study. After medical examinations and required investigations, a
      weekly dose of 25-100mg sildenafil (50 mg per week on average) was prescribed for
      patients. IOP in these patients was measured by an ophthalmologist before, one
      month after and three months after taking medication respectively. Finally, data
      were analyzed by SPSS version 16 using repeated measures test. RESULTS: Mean IOP
      before taking medication as well as one month and three months after taking
      sildenafil was 14.88+/-1.3, 15+/-1.28 and 15+/-1.34 mmHg respectively. Analysis
      of results showed that the difference in IOP in various periods of measurement
      was significant (p<0.001). Mean IOP before taking sildenafil was significantly
      different from three months after taking it (p<0.001) and mean IOP one month
      after taking sildenafil was significantly different from three months after
      taking it (p=0.002). CONCLUSION: Results of this study indicated that taking
      sildenafil for three months increased IOP. Although these changes may not be
      clinically significant.

PMID- 29038702
TI  - The effect of Teucrium polium on the duration of menstrual bleeding: A triple
      blind placebo-controlled clinical trial.
AB  - BACKGROUND: Teucrium polium (T. polium; locally called 'kalpooreh') is a herbal
      medicine with therapeutic effects against diabetes and fungal infections, and it
      has analgesic and anti-inflammatory effects as well. It is also used
      traditionally as a remedy in treating headache, dysmenorrhea, convulsions and
      gastrointestinal disorders. Moreover, its hypoglycemic, hypolipidemic and
      antibacterial effects have been reported in recent studies. OBJECTIVE: To compare
      the effectiveness of T. polium on reduction of menstrual bleeding. METHODS: This
      triple-blind, clinical trial study was performed on 70 single female students
      between 20 and 30 years old, studying at Shahid Beheshti University of Medical
      Sciences. They were allocated randomly into two groups: In the T. polium group (n
      =35), they received 250 mg of T. polium powder compared to 35 subjects who
      received placebo. For the first 3 days of menstruation, subjects were asked to
      take the capsules they had been given, four times daily for two consecutive
      menstrual cycles. Duration of menstrual bleeding was determined by a Higham
      chart. Data were analyzed by IBM-SPSS version 20, using repeated measures and
      Mann-Whitney U test. RESULTS: There were no differences between the two groups at
      baseline. Comprising the Higham chart showed that: the participants in the T.
      polium group had lower significant duration and amount of menstrual bleeding in
      the 1st and the 2nd menstruation cycles after treatment (p<=0.05). CONCLUSION:
      Teucrium polium, when taken during the first 3 days of menstruation, led to a
      significantly greater decrease in duration of menstrual bleeding compared to
      placebo. TRAIL REGISTRATION: The trial was registered at the Thailand Registry of
      Clinical Trials with the ID TCTR20160818002. FUNDING: This research received
      financial support from Shahid Beheshti University of Medical Sciences.

PMID- 29038703
TI  - Mental challenges of nurses in the face of unlearning situations in hospitals: A
      qualitative study.
AB  - BACKGROUND: The unlearning process is complex and sometimes painful in nature.
      This process usually occurs in social interactions and is very dependent on
      social contexts and the work environment. OBJECTIVE: To explore the concerns and
      mental challenges in facing unlearning situations in nurses. METHODS: This
      qualitative study using content analysis was conducted in 2013-2015. Participants
      were 25 people, and research environment was hospitals in Mashhad and Gonabad.
      The method of data collection was unstructured interview, and sampling was
      continued until data saturation. First, the recorded interviews were transcribed
      and reviewed several times. Then open codes were extracted and after reviewing
      several times, were classified into subcategories based on semantic similarity.
      Finally, the similar subcategories were put into the main categories
      semantically. RESULTS: Data analysis led to the emergence of 1,180 initial codes
      and 8 categories and 3 themes. Our themes were discouraging/encouraging
      situation, double-edged sword colleagues, and organizational policies paradox,
      that the central theme of progressive and suppressor organizational climate
      paradox were derived from them. CONCLUSION: Exposure to unlearning situations is
      a complex process of which its adoption and implementation is difficult and
      challenging. This suggests that supporting nurses and attention to their mental
      concerns and providing favorable learning conditions is required.

PMID- 29038704
TI  - Salivary flow rate and xerostomia in patients with type I and II diabetes
      mellitus.
AB  - BACKGROUND: Diabetes mellitus is one of the most prevalent metabolic diseases,
      with complications such as decreased salivary flow rate and xerostomia.
      OBJECTIVE: This study aimed to determine the salivary flow rate and xerostomia in
      type I and II diabetic patients in comparison with healthy controls. METHODS:
      This case-control study was performed on diabetic patients of a private office in
      Babol, Iran, between May 2015 and October 2016. This study involved two study
      groups (type I and II diabetes, with 40 in each group) and two control groups
      (control I and II, with 35 in each group) which were age- and sex-matched with
      the related study groups. They were all selected through simple sampling.
      Unstimulated whole saliva was collected through Navazesh method and the salivary
      flow rate was measured (ml/min). Xerostomia was evaluated via Fox's test.
      Moreover, the patients' data were recorded including age, sex, disease duration,
      type of diabetes, fasting blood glucose (FBG) and HbA1C. The obtained data were
      statistically analyzed by using SPSS version 17. Independent-samples t-test, Chi
      square, Pearson correlation and multiple comparison post-hoc tests were employed
      as appropriated. p<0.05 was considered significant. RESULTS: The mean salivary
      flow rate in type I diabetics (0.35+/-0.11 ml/min) was lower than that in control
      I (0.50+/-0.07 ml/min) (p=0.01). The same difference was observed between type II
      diabetics (0.37+/-0.13 ml/min) and control II groups (0.47+/-0.11 ml/min)
      (p=0.01). No significant difference was observed in the salivary flow rate
      between type I and II diabetics (p=0.345). Furthermore, xerostomia was higher in
      type I (2.70+/-2.50, 1.17+/-1.60) and II (2.65+/-2.20-1.62+/-1.50) diabetics
      compared with the related control groups (p=0.01), (p=0.02). CONCLUSION: Type I,
      II diabetic patients revealed lower salivary flow rate and higher xerostomia
      compared with healthy controls. The salivary flow rate and xerostomia had inverse
      correlation.

PMID- 29038705
TI  - Exploration of reproductive healthcare needs among adult men regarding sexual
      transmitted diseases and HIV/AIDS.
AB  - INTRODUCTION: One of the most important public health issues is men's sexual and
      reproductive health. Men are the most important counterparts in the prevention of
      sexual transmitted diseases and HIV/AIDS. A low level of men's referral to
      utilize healthcare services and the stigmatization of reporting sexually
      transmitted diseases in society due to cultural issues calls for the designation
      of strategies for improving the men's healthcare conditions. In addition, it is
      required to assess men's healthcare needs with consideration of cultural
      contextual, social, and economic issues. The aim of this study was to explore the
      reproductive healthcare needs of men regarding sexual transmitted diseases and
      HIV/AIDS. METHODS: This was a qualitative study with 34 men and six women from
      the general population; health policymakers, reproductive health providers, and
      clergies were collected in two large cities of Iran, including Tehran and
      Mashhad, in 2015 through individual in-depth interviews. Participants were chosen
      through purposive sampling. In-depth individual interviews were conducted to
      collect data. All interviews were transcribed verbatim and using data analysis
      through conventional qualitative content analysis. Data were analyzed using
      conventional qualitative content analysis with MAXqda. RESULTS: The data analysis
      resulted in the development of four themes and 10 categories. The themes were
      "men's educational empowerment," "appropriate sociocultural background with
      advocacy," "organizing sexual needs based on sexual ethics, religious doctrine
      and women's empowerment," and "meeting men's preventive, caring and welfare
      needs." CONCLUSION: Because men's reproductive health is intertwined with public
      health, data collected regarding men's healthcare needs with the consideration of
      social and cultural factors can be used for designing strategies for reducing the
      incidence/prevalence rates of STDs and HIV/AIDS.

PMID- 29038706
TI  - Thoracic aortic involvement in cystic echinococcosis: A case report.
AB  - Cystic echinococcosis is a common parasitic disease in some areas and involves
      different organs with different presentations. Rural areas in our country are
      endemic with this disease. We present a case of echinococcal aortic involvement
      that was diagnosed incidentally by a routine chest radiogram as a mediastinal
      mass. Cystic echinococcosis was established as final diagnosis after magnetic
      resonance imaging (MRI) and ELISA studies. The patient was treated surgically
      through a thoracotomy and her aortic defect was repaired during the operation.
      She has been asymptomatic and complication free in physical examination and
      imaging study in follow up periods after two years. Awareness of various
      presentations of the disease is necessary for physicians who are occupied in
      endemic areas. It is rational to treat echinococcal cysts adjacent to the great
      vessels with the cooperation of a vascular surgeon.

PMID- 29038707
TI  - Prevalence of idiopathic hypercalciuria in children with urinary system related
      symptoms attending a pediatric hospital in Bandar Abbas in 2014.
AB  - BACKGROUND: Idiopathic hypercalciuria is a group of diseases which can be
      manifested with urinary symptoms. Its importance is due to high prevalence,
      recurrent infections, and stone formations which are often asymptomatic.
      OBJECTIVE: The objective of this study was to determine the prevalence of
      idiopathic hypercalciuria in children with urinary system related symptoms in
      Bandar Abbas in 2014. METHODS: This descriptive cross-sectional study was done in
      2014 in a children's hospital in Bandar Abbas (southern Iran) on 321 children who
      were between 2 months to 14 years old. Random morning urine sample was obtained
      from all the patients, and calcium to creatinine ratio was assessed for all the
      patients for two times. Hypercalciuria is defined as urinary calcium excretion
      rate that is greater than 4 mg/kg per 24 hours in a child older than two years of
      age. Data was analyzed using IBM SPSS statistics 23.0 software and Chi-square and
      independent-samples t-test. RESULTS: Among the 321 children assessed, 153 (47.7%)
      had idiopathic hypercalciuria. The mean age of the children with idiopathic
      hypercalciuria was 55.20+/-43.71. Prevalence of idiopathic hypercalciuria was
      48.3% in children with urinary tract infection, 54.9% and 53.6% in children with
      microscopic and macroscopic hematuria respectively, In children with dysuria,
      there were 52.1%, and 51.8% in children with frequency, 49.1% in children with
      kidney stone which was confirmed with sonography, 28.6% and 37.5% in children
      with nocturnal and daily urinary incontinency respectively. Results of this study
      showed no significant relationship between urinary system symptoms and idiopathic
      hypercalciuria (p>0.05). CONCLUSION: Hypercalciuria can be presented with
      different symptoms associated with urinary symptoms. Therefore, it is recommended
      to check the urinary calcium level in children with urinary symptoms with no
      definite etiology.

PMID- 29038708
TI  - Factors affecting the choice of type of delivery with breast feeding in Iranian
      mothers.
AB  - OBJECTIVE: This study assessed the factors affecting the choice of type of
      delivery with breast feeding in Iranian mothers. METHODS: This Cross section
      descriptive analytic study was performed using a random sampling technique, using
      data from 400 pregnant women who attended the maternity centers in Borazjan and
      Kazerun in Iran in 2014. A questionnaire covering demographic characteristics,
      mode of delivery and postpartum conditions was completed for each mother.
      Descriptive analysis and Chi square test were used along with SPSS 23 software to
      statistically analyze the data and p-value less than 0.05 was considered for
      statistical significance. RESULTS: In this study, the rate of normal delivery and
      cesarean operation are considered equal. In the main factors influencing the
      choice of delivery, mothers' education level (p=0.028) and pregnancy status
      (p=0.041) showed a significant relationship. Although no significant association
      between child nutrition with the type of delivery was found, duration of
      breastfeeding with the type of delivery showed significant association (p=0.046).
      CONCLUSION: Although cesarean delivery in many cases is life-saving for mother
      and fetus; in addition to medical indications, parents with higher education and
      pregnancy status are also important factors in increasing the rate of cesarean
      section compared to vaginal delivery. Babies of mothers with normal delivery had
      a longer time of breastfeeding. Further studies in Iran are necessary, regarding
      the reasons for high cesarean section and their outcomes.

PMID- 29038709
TI  - Psychological empowerment of NGO women in Iran: Designing a tool.
AB  - BACKGROUND: As the core of health promotion, proper assessment of empowerment is
      a base for planning for a process that increases people's control on their
      decisions, lifestyle, and effective activities for their health. OBJECTIVE: To
      design and develop a special tool to assess the empowerment of NGO women in Iran.
      METHODS: This successive exploratory study of combinational type was conducted in
      2015 in two steps. In the first step, using comments of participants and the help
      of authentic texts related to this field, dimensions of psychological empowerment
      were developed. In the second step, psychometric properties of the scale or tool
      were determined using formal content, and structural validity and reliability
      were determined using internal consistency and stability via SPSS version 21.
      RESULTS: In the first step, the initial tool including 58 items was developed in
      the form of eight domains. In the second step, based on exploratory factor
      analysis (EFA), the number of items was reduced to 37. Considering the
      eigenvalues of higher than one, items were classified into eight factors. KMO
      index was 0.896 in this study. Reliability of the tool was 0.81 using Cronbach's
      alpha. This tool is able to predict 66.1% of total changes in psychological
      empowerment. CONCLUSION: A questionnaire with relevant reliability and validity,
      including eight domains of participation, motivation, cognitive thinking,
      critical thinking, self-efficacy, intention, perceived control and social support
      was developed to measure psychological empowerment of NGO women in Iran.

PMID- 29038710
TI  - Promoting physical activity in Iranian women: A qualitative study using social
      marketing.
AB  - BACKGROUND AND AIM: In social marketing, at the center of the program is consumer
      perception. The objective of this study was to explore the viewpoints of Iranian
      women for tailoring interventions so as to increase physical activity. METHODS:
      The social marketing model served as the framework of the study. Qualitative data
      were collected via six semi-structured focus group discussions (FGDs), in 2014 in
      Iran. Participants were 51 women, 20 to 60 years old, selected by purposive
      sampling, with a maximum diversity. Qualitative content analysis of the data was
      conducted by researchers. RESULTS: After data analysis and extracting initial
      codes, they were all categorized in four predefined categories of social
      marketing model (product, price, place and promotion) and related sub-categories.
      Most of the participants were inactive. Price was addressed by women as the
      dominant category of this study. The majority of participants emphasized the
      benefits of prevention of chronic diseases, fitness, staying young, and improving
      family relations. Most women preferred to do physical activity in a secure and
      enclosed female environment. And the majority of participants considered radio,
      television, face to face training, texting, and advertising billboards as
      promotional strategies. CONCLUSION: This study provides a unique insight into
      consumers' values and motivations that affect consumers' decisions to adopt
      physical activity, in Iran. It could also help researchers to design and
      implement intervention programs to increase physical activity.

PMID- 29038711
TI  - Study of the C677T and 1298AC polymorphic genotypes of MTHFR Gene in autism
      spectrum disorder.
AB  - BACKGROUND: Autism is currently known as "a behaviorally defined syndrome"
      manifested as impairment in social communication, repetitive routines and
      restricted interests. There is an increased risk of ASDs associated with common
      mutations affecting the folate/methylation cycle. AIM: The aim of this study was
      to identify C677T and 1298AC polymorphic genotypes of MTHFR gene among a sample
      of Egyptian children with autism and to make a phenotype-genotype correlation for
      the autistic patients. METHODS: This case-control study was carried out from 2013
      through 2015. The study included 31 children with autism and 39 children in a
      normal control group, the mean age of patients and control was comparable (4.5
      years+/- 2) with males predominant in both groups. We used DSM-V-TR criteria,
      Stanford-Binet intelligence scale V and childhood autism rating scale (CARS) for
      assessments. Genotyping for MTHFR gene polymorphic loci C677T and 1298AC was
      performed on amplified DNA by PCR with subsequent reverse hybridization and
      restriction fragment length polymorphisms analysis. Data were analyzed by SPSS
      version 11, using Chi-Square, independent-samples t-test, and ANOVA. RESULTS:
      There was significant relationship between low birth weight and occurrence of
      autism (p<0.01), and between delayed motor and social milestones in cases of
      autism compared to controls (p<0.01). Heterozygosity for A1298C polymorphism was
      highest among patients (41.9%) followed by 35.5% mutant genotype CC and 22.6%
      normal AA (wild) type and Allele C was detected in patients more than in control
      (56.45% vs. 11.54%) (p<0.001). For C667T polymorphism, heterozygosity was also
      highest among patients (48.4%) followed by wild type genotypes C677 (38.7%) and
      12.9% for mutant genotypes 667T. Allele T appeared more in patients than control
      (31.10 %vs. 5.13%) (p<0.00). Heterozygosity for CT and A-C genotypes were
      detected equally (46.2%) among patients with severe autism (according to CARS).
      CONCLUSION: There is a significant association between severity and occurrence of
      autism with MTHFR gene polymorphisms C677T and A1298C. Further studies are needed
      on a larger scale to explore other genes polymorphisms that may be associated
      with autism, to correlate the genetic basis of autism.

PMID- 29038712
TI  - Prevalence of diabetes and its relation with age and sex in Turaif city, northern
      Saudi Arabia in 2016-2017.
AB  - BACKGROUND: The prevalence of diabetes in Saudi Arabia has increased dramatically
      during the last decades. This increase has been attributed to significant changes
      in cultural and socio-economic factors. OBJECTIVE: The aim of this study was to
      determine prevalence of diabetes and its relation with age and sex in Turaif
      city, northern Saudi Arabia. METHODS: This was a cross-sectional study carried
      out during the academic year 2016-2017 over a period of 6 months (October 01,
      2016 to March 30, 2017). A total of 1,287 Saudi national individuals of both
      sexes, aged from 1 year to more than 65 years were included in the study. Data
      were collected by a predesigned questionnaire covering medical history of
      diabetes, age and sex. RESULTS: Mean age (+/- SD) was 24.29 (+/-13.96) years with
      the minimum age at 1 year and the maximum age at 93 years, male to female ratio
      was 42.5% to 57.5%. The total prevalence of DM among the studied population was
      5.8% and pre-diabetic cases were 6.8%. There were significant relationships
      between age/sex, and the occurrence of diabetes among the studied population
      (p<0.05). CONCLUSIONS: The total prevalence rate of DM among the studied
      population of Turaif city, northern Saudi Arabia was 5.8% and pre-diabetic cases
      were 6.8%. Awareness campaigns and prevention programs about diabetes should be
      instituted and the existing ones must be strengthened. Adequate commitment from
      the Ministry of Health is also advocated.

PMID- 29038713
TI  - Coexistence of lupus nephritis and sickle cell trait, an electron microscopic
      assessment of renal glomerular damage: Case report of a rare association.
AB  - Because of similarities of the musculoskeletal, central nervous system, and renal
      manifestations in both diseases, diagnosing systemic lupus erythematosus (SLE) in
      sickle cell disease (SCD) patients can be difficult to establish. Although Sickle
      Cell Trait (SCT) is still considered a benign form of SCD, its impact on kidney
      injury and other renal manifestations is well recognized in the literature. In
      this case report, we look at the challenges that develop when diagnosing patients
      with a concurrence of both diseases and the importance of early recognition and
      treatment of lupus nephritis in SCT patients. We present a case of a male patient
      with sickle-cell trait who was admitted to our hospital complaining of low grade
      fever and pancytopenia for investigations proven to be SLE. A renal biopsy on
      electron microscopy assessment with different staining modalities as well as
      immune fluorescence revealed mixed pathological changes. We emphasize the
      importance in considering the presence of a coexisting autoimmune disease in a
      patient with sickle hemoglobinopathies even in the milder forms like SCT which
      may display an atypical and/or multisystem presentation. Also, the impact of the
      two conditions on the renal pathological changes should be expected to be more
      damaging even at early onset of SLE flare, and hence, an urge to start with more
      intensified immunosuppressive medications.

PMID- 29038714
TI  - Ear diseases and factors associated with ear infections among the elderly
      attending hospital in Arar city, Northern Saudi Arabia.
AB  - BACKGROUND: Changes in the anatomical structures and function of the ear can
      result in ear diseases, and may affect all age groups including the elderly as a
      result of aging. OBJECTIVE: To identify the frequency and types of ear diseases
      among the elderly attending Abdullah bin Abdul-Aziz bin Musa'ed Al Saud hospital,
      Arar city, in the Northern Province of KSA, and factors associated with ear
      infections among them. METHODS: This cross-sectional hospital based study
      conducted from December 2016 through May 2017 included 138 elderly participants.
      A questionnaire was designed for collecting data about socio-demographic
      variables, the frequency and types of ear diseases among participants, and
      factors associated with ear infections among them. Data were analyzed by SPSS
      version 15, using descriptive statistics and Chi-Square test. RESULTS: Findings
      showed that 49.3% of the participants were suffering from ear disease. Hearing
      impairment was detected in 37% of the elderly people studied. In addition, 9.4%
      and 2.9 % of the participants suffered from otitis media and otitis interna,
      respectively. None of the studied factors had a significant effect on the
      development and pattern of ear infection among the studied population.
      CONCLUSION: Ear diseases were found among the participants with variable rates.
      More than one third of respondents suffered from hearing impairment. Ear
      infections were detected in lower rates. Although these problems are not life
      threating, they negatively impact the quality of life, and measures are needed
      for prevention and control.

PMID- 29038715
TI  - One-stage surgical excision of a huge bilateral multiple osteochondroma of the
      hip: a case report.
AB  - Osteochondroma or hereditary multiple exostoses is the most common benign bone
      tumor and is usually found in young patients. Osteochondromata of the proximal
      femur or hip have been reported in 30% to 90% of patients with hereditary
      multiple exostoses. This article presents a 25-year-old-male referred to our
      orthopedic clinic with a complaint of pain in both groins for the last four years
      which has deteriorated in the past 6 months by limitation of range of motion.
      Radiographic findings were consistent with huge hip osteochondroma and a
      histopathological report confirmed the diagnosis. This was a case of a huge
      bilateral osteochondroma of the hip originating from the posterior of the hips to
      the neck of the femur and hip joints and part of proximal of femur, that
      underwent one-stage surgical excision of the tumor with posterior approach and
      tumor resection. As we know, this case of bilateral huge hip osteochondromas has
      rarely been presented previously by someone who has undergone one-stage surgery
      treatment of a tumor this size. Bilateral hip osteochondroma is a rare condition
      and we showed that one-stage excision can be performed successfully.

PMID- 29038716
TI  - Relationship between a network's indicators and basic factors with high-risk
      behavior of injection among injecting drug users (IDU) via the multiple
      membership multilevel model.
AB  - BACKGROUND: Among various methods and types of drug abuse, injection receives a
      great deal of importance because of its related dangerous behavior and health
      consequences. It seemed that some of the network's indicators affect dangerous
      behavior of injection. OBJECTIVE: To determine the relationship between a
      network's indicators and basic factors with high-risk behavior of injection among
      injecting drug users (IDU) via the multiple memberships multilevel model.
      METHODS: In this cross-sectional study, the data related to 147 IDUs in Kerman
      province, who were interviewed from October 2013 through March 2014, were used,
      and these addicts were chosen for interview from specific resorts used for common
      injection. In this study, for analyzing data, multiple membership multilevel
      model and MLwiN 2.02 software were used. RESULTS: In this study, the mean age of
      people, who were mostly men, was 37.2+/-9.02. Based on the result, it becomes
      obvious that variables of in-degree with OR=1.49 (p=0.006) and the whole number
      of people related to the person with OR=1.18 (p=0.003) influences the high-risk
      behavior of injection. Also, none of the demographic variables influenced the
      high-risk behavior of injection. CONCLUSION: Totally based on the results of this
      study, one can find a suitable method in the social network of IDUs in order to
      create essential strategies, reducing the risk throughout the country. In
      addition, in minimum time with fewer expenses, aggravation of dangerous behavior
      especially high-risk behavior of injection can be prevented.

PMID- 29038717
TI  - Acceptability of picture archiving and communication system (PACS) among hospital
      healthcare personnel based on a unified theory of acceptance and use of
      technology.
AB  - BACKGROUND AND AIM: The picture archiving and communication system (PACS) is a
      healthcare system technology which manages medical images and integrates
      equipment through a network. There are some theories about the use and acceptance
      of technology by people to describe the behavior and attitudes of end users
      towards information technologies. We investigated the influential factors on
      users' acceptance of PACS in the military hospitals of Tehran. METHODS: In this
      applied analytical and cross-sectional study, 151 healthcare employees of
      military hospitals who had experience in using the PACS system were investigated.
      Participants were selected by census. The following variables were considered:
      performance expectancy, efforts expectancy, social influence, facilitating
      conditions and behavioral intention. Data were gathered using a questionnaire.
      Its validity and reliability were approved by a panel of experts and was piloted
      with 30 hospital healthcare staff (Cronbach's alpha =0.91). Spearman correlation
      coefficient and multiple linear regression analysis were used in analyzing the
      data. RESULTS: Expected performance, efforts expectancy, social impact and
      facilitating conditions had a significant relationship with behavioral intention.
      The multiple regression analysis indicated that only performance expectancy can
      predict the user's behavioral intentions to use PACS technology. CONCLUSION:
      Performance and effort expectancies are quite influential in accepting the use of
      PACS in hospitals. All healthcare personnel should become aware that using such
      technology is necessary in a hospital. Knowing the influencing factors that
      affect the acceptance of using new technology can help in improving its use,
      especially in a healthcare system. This can improve the offered healthcare
      services' quality.

PMID- 29038718
TI  - Effects of a theory-driven educational package and social support on durability
      of cigarette smoking cessation behavior: A community-based program.
AB  - BACKGROUND: According to a World Health Organization (WHO) report, the prevalence
      of smoking in Iranian individuals aged 15-64 is up to 12%. OBJECTIVE: The aim of
      the current study was to determine the durability of smoking cessation behavior
      based on a trans-theoretical model. METHODS: This educational experimental study
      was conducted on smokers in Khomein City, Iran, in 2015. Sampling was done
      through a public announcement and then a random allocation of participants into
      two study group (50 persons) and control group (60 persons). Tools to gather data
      were as follows: an individual characteristics form and DiClemente's stages of
      change, Velicer's self-efficacy, Prochaska's processes of change, Velicer's
      decisional balance, and Fagerstrom's nicotine dependency questionnaires. The
      study group received five sessions of 45-minute individual counseling each and
      were followed-up three and six months later. Data were analyzed by SPSS version
      16, using paired-samples t-test, independent-samples t-test, and chi-square.
      RESULTS: Within six months of follow-up, 20 persons (40%) of the intervention
      group reached the maintenance stage of smoking cessation, while no one from
      controls managed to do that. Except for the perceived barriers and benefits of
      smoking cessation, all other constructs of the trans-theoretical model (cognitive
      and behavioral processes and smoking temptation) showed significant changes among
      the intervention group during six months' follow-up (p<0.05). There was no
      significant relationship between variables of having smoker friends, occupation,
      marital status, education status, and success or failure in cigarette smoking
      cessation (p>0.05). CONCLUSION: According to our study, selection of cigarette
      smokers who are willing to quit, delivery of individual counseling according to
      specific personal characteristics, and also provision of free nicotine
      replacement therapies should be taken into account in cigarette smoking cessation
      programs.

PMID- 29038719
TI  - Phenomenological needs assessment of parents of children with cochlear implants.
AB  - BACKGROUND: The use of cochlear implants has been a remarkable success in
      reducing disabilities in those with impaired hearing, which have made a
      significant change in the patients' quality of life. Only by relying on cochlear
      implants, disabilities cannot be eliminated in the hearing impaired, and,
      alongside this intervention, rehabilitation practices such as through family and
      community support are necessary. AIM: To explain the needs of parents of children
      with cochlear implants to increase the quality of rehabilitation services and
      family-based interventions. METHODS: A descriptive phenomenology study was
      performed with the participation of 16 people, including eight mothers, three
      fathers, and five experts involved with the rehabilitation of children aged 2-7
      years with cochlear implants. The research setting was centers with speech
      therapy service providers for hearing-impaired children in the city of Shiraz
      (Iran) in 2015. Information was gathered through in-depth interviews with
      participants and analyzed by using Colaizzi's nine-step analysis method and
      MAXQDA (Ver10) applications. RESULTS: The mean age of participants was 34 years,
      and the average age of diagnosis of hearing problems in children was 12 months.
      The obtained data from the analysis of interviews about the needs of parents of
      children with cochlear implants were categorized into 19 sub-contents and five
      contents, as follows: the need for access to health care services; psychological
      needs; mood-related needs of a child; educational needs and financial
      requirements. CONCLUSION: Parents of children with cochlear implants have
      numerous needs, and they encounter problems based on their situation and
      experiences. The results indicate the necessity of close cooperation among
      different professionals such as an audiologist, pediatrician, psychologist, and
      speech therapist for the program's success.

PMID- 29038720
TI  - Epidemiology of senile prostatic enlargement among elderly men in Arar, Kingdom
      of Saudi Arabia.
AB  - BACKGROUND AND AIM: Senile prostatic enlargement due to benign prostatic
      hyperplasia (BPH) is a common problem among older men, and is responsible for
      considerable disability. This study was conducted to determine the prevalence and
      determinants of the clinically diagnosed prostatic enlargement among elderly men
      in Arar, Northern Saudi Arabia. METHODS: This cross-sectional study was carried
      out on all consented elderly males attending the outpatient clinic of the urology
      department of Arar Central Hospital from February 2017 to July 30, 2017. Each
      participant underwent a general examination and digital per rectal to detect
      general chronic diseases, obesity and prostatic enlargement. Data were analyzed
      by SPSS version 16, using descriptive statistics and Chi-squared test. RESULTS:
      Among 81 elderly male participants in the study, 19.8% had clinically diagnosed
      senile prostatic enlargement (SPE) and 3.7% had prostatic tumors. There was
      significant relation between SPE and age as 6.2% of cases were 60-69 years, 43.8%
      were 70-79 years and 44.0% were 80 years or more (p<0.05). There was also
      significant relation between SPE and obesity as 62.5% of cases were obese and
      37.5% were non obese (p<0.05). There was no significant relation with marital
      status, smoking or diabetes mellitus (p<0.05). CONCLUSION: Senile prostatic
      enlargement is one of the significant important issues in public health in Arar
      city, Northern Saudi Arabia. The prevalence of this condition reaches 19.3%,
      thereby placing even greater burden on the quality of life of the elderly and on
      the health system in the region.

PMID- 29038721
TI  - Gender differences in substance use patterns and disorders among an Iranian
      patient sample receiving methadone maintenance treatment.
AB  - BACKGROUND: The current prevalence rate of substance abuse and dependence,
      represents an increasing trend of substance abuse and dependence among women, and
      the results of epidemiology studies indicate that substance use patterns are
      different between men and women. This study aimed to determine gender differences
      in substance use patterns and disorders among the patients undergoing methadone
      maintenance treatment. METHODS: This cross-sectional study was conducted
      throughout a specified time bracket ranging from September 2012 through March
      2013 in Methadone Maintenance Treatment (MMT) clinics of Mashhad, Iran. In this
      study, 140 men and 120 women were selected from among the patients referring to
      MMT clinics in Mashhad through purposeful sampling method. The sample units were
      assessed using a demographic information questionnaire and Structured Clinical
      Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID). The
      data were then analyzed by Chi Square test, Mann-Whitney U test, and Independent
      samples t-test. SPSS software 16 was used to conduct statistical analyses with P
      values less than 0.05 regarded as significant. RESULTS: The results showed that
      men and women are significantly different from each other in terms of marital
      status (p=0.001), education (p=0.001), income (p=0.001), history of injection
      (p=0.002), imprisonment (p=0.001), and substance use abstention (p=0.023). It was
      also revealed that methamphetamine dependence (p=0.017) and simultaneous use of
      multiple substances (p=0.001) in the past 12 months were diagnosed, to a larger
      extent, in male participants than those in female participants. In addition, the
      diagnoses of nicotine dependence (p=0.001), cannabis abuse (p=0.001), heroin
      dependence (p=0.001), and substance abuse and alcohol dependence (p=0.001) during
      a lifetime were more frequently existing in males than those in females.
      CONCLUSION: There are gender differences in substance use patterns and disorders
      that appear to be caused by the degree of access to substances and the impacts of
      cultural and social aspects on men and women in Iran.

PMID- 29038722
TI  - A comparison of body image concern in candidates for rhinoplasty and therapeutic
      surgery.
AB  - BACKGROUND: Body dysmorphic disorder among patients referring for cosmetic
      surgeries is a disorder that if not diagnosed by a physician, can cause
      irreparable damage to the doctor and the patient. OBJECTIVE: The aim of this
      study was to compare body image concern in candidates for rhinoplasty and
      therapeutic surgery. METHODS: This was a cross-sectional study conducted on 212
      patients referring to Loghman Hospital of Tehran for rhinoplasty and therapeutic
      surgery during the period from 2014 through 2016. For each person in a cosmetic
      surgery group, a person of the same sex and age in a therapeutic surgery group
      was matched, and the study was conducted on 60 subjects in the rhinoplasty group
      and 62 patients in the therapeutic surgery group. Then, the Body Image Concern
      Inventory and demographic data were filled by all patients and the level of body
      image concern in both groups was compared. Statistical analysis was conducted
      using SPSS 16, Chi-square test as well as paired-samples t-test. P-value of less
      than 0.05 was considered statistically significant. RESULTS: In this study, 122
      patients (49 males and 73 females) with mean age of 27.1+/-7.3 between 18 and 55
      years of age were investigated. Sixty subjects were candidates for rhinoplasty
      and 62 subjects for therapeutic surgery. Candidates for rhinoplasty were mostly
      male (60%) and single (63.3%). Results of the t-test demonstrated that body image
      concern and body dysmorphic disorder were higher in the rhinoplasty group
      compared to the therapeutic group (p<0.05). CONCLUSION: Results of this study
      showed that the frequency of rhinoplasty candidates is higher in single male
      subjects. In addition, body image concern was higher in rhinoplasty candidates
      compared to candidates for other surgeries. Visiting and correct interviewing of
      people who referred for rhinoplasty is very important to measure their level of
      body image concern to diagnose any disorders available and to consider required
      treatments.

PMID- 29038723
TI  - Survey of awareness of diabetes mellitus among the Arar population, Northern
      Border Region of Saudi Arabia.
AB  - BACKGROUND: Diabetes Mellitus (DM) is one of the most widely prevalent diseases
      in Saudi Arabia. Health education is considered an essential component to improve
      knowledge and change behavior. People affected by diabetes often have inadequate
      knowledge about the nature of diabetes, its risk factors and associated
      complication. OBJECTIVES: The aim of this study was to assess the awareness of
      the Arar population with various aspects of diabetes mellitus. METHODS: A cross
      sectional study was carried out in Arar city, the capital of the Northern
      Province of Kingdom of Saudi Arabia (KSA). The study was carried out on Saudi
      nationals from different age groups that were selected by systematic random
      sampling. Data was collected by means of personal interview with the participants
      using a pre-designed questionnaire which was administered by the medical students
      for each diabetic patient. Data were analyzed by SPSS version 15, using
      descriptive statistics and Chi-square test. RESULTS: A total of 702 participants
      were interviewed, among them 201 (28.6%) males and 501 (71.4%) females, and most
      of them (77.8%) had high educational level, 10.4% were diabetics, 78.9% did not
      have regular checkup visits to the doctor and 58.5% did not perform any regular
      exercises, including walking, 60% thought that DM was due to partial or total
      decrease in insulin secretion and 12.4% thought that it was due to excess sweet
      eating. Additionally, 48.7% of the respondents thought that lack of exercise and
      obesity were the major risk factors of DM, 33.2% thought that it was a genetic
      disease. The majority (86.3) of the participants believed that the treatment of
      DM was a combination of healthy diet, exercise and medication and more than half
      (63.1%) said that weight loss and modification of life style were the most
      important preventive measures of DM. Regarding participants' knowledge about DM
      complications, 24.5% knew about retinopathy and loss of vision, 8.3% knew about
      retinopathy, loss of vision, low sensation and numbness in extremities, 24.9%
      said that symptoms of DM were thirst and frequent urination. CONCLUSION: This
      study recommends that health policy makers conduct more effective health
      education sessions to increase knowledge of diabetic patients and their
      caregivers about diabetes and the importance of compliance with its treatment.

PMID- 29038724
TI  - Idiopathic granulomatous mastitis: dilemmas in diagnosis and treatment.
AB  - BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a benign rare inflammatory
      disease of the breast. Due to its uncommon etiology, diagnosis and treatment is
      still unknown. Selection of a standard method for diagnosing idiopathic
      granulomatous mastitis is sophisticated. In view of non-definitive clinical and
      imaging finding, histopathology is the cornerstone of definitive diagnosis.
      OBJECTIVE: To determine and help solve the dilemma of treatment and diagnosis of
      idiopathic granulomatous mastitis. METHODS: This historical cohort study was
      conducted on 48 patients who referred to the general surgery clinic of Imam
      Khomeini Hospital of Urmia, were diagnosed with IGM and were histopathologically
      selected by census using the registry system, in Urmia city, Iran, during 2010
      2015 so that medical reports, ultrasonography (US) and mammography (MMG)
      findings, follow-up information and recurrence rate were obtained from records.
      The data were analyzed using SPSS software version 18 and descriptive statistics
      were used. RESULTS: According to records, 68.75% of patients (n=33) had palpable
      mass, 45.83% of patients (n=22) had breast pain and swelling, erythema and 20.83%
      of patients (n=10) had purulent drainage. Of the 48 patients 12 (25%) had
      mammography, which revealed the following findings: mass with irregular border in
      6 patients, skin thickness in 2 cases (4.16%), and parenchymal asymmetry in 4
      cases (8.33%). Minimum follow-up was 24 (range 24-56) months. CONCLUSIONS:
      According to our findings, histopathology of the disease is fundamental for
      correct diagnosis. Steroid therapy as a therapeutic method such as prednisolone
      was an effective and applicable choice in the treatment of idiopathic
      granulomatous mastitis by decreasing in inflammation.

PMID- 29038725
TI  - Caregiving burden of children with chronic diseases.
AB  - BACKGROUND: The care demands of children with chronic diseases can affect
      caregivers' health by imposing caregiving burden to them. The health status of
      caregivers plays a vital role in the quality of care provided to such children
      and in their quality of life. OBJECTIVE: To determine caregiving burden in
      caregivers and to identify relevant influential factors. METHODS: In this cross
      sectional study, a total number of 249 caregivers of children with chronic
      diseases who referred to hospitalization and ambulatory departments of Bandar
      Abbas, Iran in 2016 were selected using convenience sampling method. The main
      caregivers who were older than 18 years and provided care to a sick child for at
      least three months consecutively were included. Caregiving burden was measured
      using the Caregiver Burden Scale. Data was analyzed SPSS 16 using descriptive
      statistics, Spearman's correlation coefficient and Mann-Whitney U test. RESULTS:
      Mean score of caregiving burden was 1.98 which was close to moderate level. The
      highest caregiving burden was observed in general strain dimension (2.35), and
      cerebral palsy imposed the maximum burden to caregivers (2.24). Correlation
      coefficient revealed that perceived caregiving burden was in connection with
      children's and caregivers' age, duration of disease and caregiving, child's level
      of disability, number of family members and income level (p<0.05). Mann-Whitney U
      test showed that female caregivers, villagers, and caregivers dealing with more
      than one patient experienced higher burden (p<0.05). CONCLUSION: Different
      variables can increase caregiving burden. Therefore, planning for holistic and
      family-centered interventions to decrease caregiving burden is necessary for
      health care providers.

PMID- 29038726
TI  - Knowledge, attitudes and practices toward prevention of hepatitis B virus
      infection among medical students at Northern Border University, Arar, Kingdom of
      Saudi Arabia.
AB  - BACKGROUND AND AIM: Health care workers' risk of occupational exposure to HBV is
      a chief concern, particularly with young students in the health profession. This
      study was carried out to assess the knowledge regarding symptoms, risk factors
      and prevention of hepatitis B virus infection among medical students. METHODS: A
      cross-sectional study was carried out from November 01, 2016 to May 30, 2017 on
      medical students at the Northern Border University (Arar, Kingdom of Saudi
      Arabia). Data were collected from 200 students from all academic years using pre
      designed questionnaire which included questions designed to fulfill the study
      objectives. RESULTS: Regarding students' knowledge about hepatitis B infection,
      81% of them knew that carriers could transmit infection, 89.5% of them knew that
      it could not be spread by casual contact, 80% by contact with open wound, 96.5%
      by contaminated blood and body fluids, 92.5% by unsterilized syringe, needle and
      surgical instruments and 79.5% by unsafe sex. In total, 86.5% of students knew
      that a vaccine could prevent HBV infection, 95% knew it had been laboratory
      tested, 64% knew HBV had post exposure prophylaxis and only 55% knew that it
      could be cured. In all, 75.5% of students knew that HBV caused liver cancer.
      Regarding attitude, 23% of students said they had no concern of being infected
      with HBV, 86.5% agreed that HBV vaccine was safe and effective and 90% believed
      that following infection, control guidelines would protect them from being
      infected by HBV at work. Regarding practice, only 56.5% of students had screened
      for HBV infection 22% had had a needle prick injury but 68% would report that
      injury. Furthermore, 69.5% have received HBV vaccine but only 38% of them had
      received 3 doses. CONCLUSION: The students' knowledge of the hepatitis B virus
      was found to be good. We recommend improving knowledge, attitude and practice of
      the public as well as students, through health education campaigns and settings.

PMID- 29038727
TI  - Left ventricular torsional parameters before and after atrial fibrillation
      ablation: a velocity vector imaging study.
AB  - BACKGROUND AND AIM: Effects of atrial fibrillation (AF) and its ablative
      treatment on LV torsion have not yet been fully investigated. This study aimed to
      examine whether AF patterns of LV contraction and its ablative correction can
      exert a significant impact on LV torsion by velocity vector imaging (VVI).
      METHODS: This case-control study conducted in Rajaie Cardiovascular, Medical and
      Research Center between October 2012 and June 2013. Study participants were 30
      consecutive patients with symptomatic paroxysmal AF who met the inclusion
      criteria. The control group included 24 healthy participants with no history of
      cardiovascular disease. All individuals were in sinus rhythm at the time of
      echocardiography before and after the ablation procedure. Two-dimensional (2D)
      and Doppler echocardiography on a commercially available ultrasound system was
      performed for all the patients. Scanning was done by a wide-band ultrasound
      transducer with the frequency range between 2.5-3.5 MHz. The two short-axis views
      at basal and apical levels were subsequently processed off-line by VVI XStrain
      software. In order for data analysis, SPSS 16 utilized using paired and
      independent t-test. p-value <=0.05 was considered significant. RESULTS: LV
      torsion ( degrees /cm) mean +/- SD was significantly lower in paroxysmal AF
      patients before ablation (0.8+/-0.3) than the control group (1.5+/-0.4) (p<0.001)
      and increased significantly after ablation (1.1+/-0.5) compared with before
      ablation (p=0.004), but still significantly lower than the control group
      (p=0.003). LV Twist, twist rate and untwist rate mean +/- SD were significantly
      lower in paroxysmal AF patients before ablation than the control group and
      increased significantly after ablation compared with before ablation, but still
      significantly lower than the control group. CONCLUSION: Subclinical LV
      dysfunction may be detected in paroxysmal AF rhythm by measuring torsional
      parameters through VVI which improves after AF ablation.

PMID- 29026521
TI  - A novel data storage logic in the cloud.
AB  - Databases which store and manage long-term scientific information related to life
      science are used to store huge amount of quantitative attributes. Introduction of
      a new entity attribute requires modification of the existing data tables and the
      programs that use these data tables. The solution is increasing the virtual data
      tables while the number of screens remains the same. The main objective of the
      present study was to introduce a logic called Joker Tao (JT) which provides
      universal data storage for cloud-based databases. It means all types of input
      data can be interpreted as an entity and attribute at the same time, in the same
      data table.

PMID- 27990268
TI  - Monitoring the compliance of the academic enterprise with the Fair Labor
      Standards Act.
AB  - Background: On December 1, 2016, the Fair Labor Standards Act (FLSA) was due to
      be updated by the U.S. Department of Labor. Key changes included an increase in
      the salary threshold for exemption from overtime for working more than 40 hours
      per week, and indexing the salary level so that it is updated automatically every
      3 years. This was predicted to have a profound effect on academe as postdoctoral
      researchers were mostly paid at a salary below the new threshold. On November 22,
      2016, an injunction was granted nationwide, delaying implementation of the
      updates, which were finally struck down entirely on August 31, 2017. Here we
      review the key changes to the FLSA, how they came about, and how the postdoctoral
      population was affected. Methods: We describe recent data collection efforts to
      uncover what institutions with postdocs were doing to comply with the FLSA.
      Results: Our data showed that 57% of institutions checked (containing 41% of the
      estimated postdoctoral workforce in science, engineering and health) had not
      decided or had no public decision available one month prior to implementation,
      and only 35.5% of institutions were planning to raise salaries to the new
      minimum. After the injunction, a number of institutions and the NIH continued
      with their plans to raise salaries. Overall, despite the removal of a federal
      mandate, approximately 60% of postdocs are at institutions whose policy is to
      raise salaries. Conclusions: Our data show uncertainty in postdoctoral salaries
      in the U.S. prior to implementation of the FLSA ruling. In addition, while some
      institutions did suspend plans to raise postdoctoral salaries after the
      injunction, many continued with the raise. The implementation of postdoctoral
      salary raises may be inconsistent, however, as the legal minimum is still
      $23,660.

PMID- 28413619
TI  - Picopore: A tool for reducing the storage size of Oxford Nanopore Technologies
      datasets without loss of functionality.
AB  - Oxford Nanopore Technologies' (ONT's) MinION and PromethION long-read sequencing
      technologies are emerging as genuine alternatives to established Next-Generation
      Sequencing technologies. A combination of the highly redundant file format and a
      rapid increase in data generation have created a significant problem both for
      immediate data storage on MinION-capable laptops, and for long-term storage on
      lab data servers. We developed Picopore, a software suite offering three methods
      of compression. Picopore's lossless and deep lossless methods provide a 25% and
      44% average reduction in size, respectively, without removing any data from the
      files. Picopore's raw method provides an 88% average reduction in size, while
      retaining biologically relevant data for the end-user. All methods have the
      capacity to run in real-time in parallel to a sequencing run, reducing demand for
      both immediate and long-term storage space.

PMID- 28979765
TI  - MicroRNAs in the development and neoplasia of the mammary gland.
AB  - Study on the role of microRNAs (miRs) as regulators of gene expression through
      posttranscriptional gene silencing is currently gaining much interest,due to
      their wide involvement in different physiological processes. Understanding
      mammary gland development, lactation, and neoplasia in relation to miRs is
      essential. miR expression profiling of the mammary gland from different species
      in various developmental stages shows their role as critical regulators of
      development. miRs such as miR-126, miR-150, and miR-145 have been shown to be
      involved in lipid metabolism during lactation. In addition, lactogenic hormones
      influence miR expression as evidenced by overexpression of miR-148a in cow
      mammary epithelial cells, leading to enhanced lactation. Similarly, the miR-29
      family modulates lactation-related gene expression by regulating DNA methylation
      of their promoters. Besides their role in development, lactation and involution,
      miRs are responsible for breast cancer development. Perturbed estrogen (E2)
      signaling is one of the major causes of breast cancer. Increased E2 levels cause
      altered expression of ERalpha, and ERalpha-miR cross-talk promotes tumour
      progression. miRs, such as miR-206, miR-34a, miR-17-5p, and miR-125 a/b are found
      to be tumour suppressors; whereas miR-21, miR-10B, and miR-155 are oncogenes.
      Oncogenic miRs like miR-21, miR-221, and miR-210 are overexpressed in triple
      negative breast cancer cases which can be diagnostic biomarker for this subtype
      of cancer.  This review focuses on the recent findings concerning the role of
      miRs in developmental stages of the mammary gland (mainly lactation and
      involution stages) and their involvement in breast cancer progression. Further
      studies in this area will help us to understand the molecular details of mammary
      gland biology, as well as miRs that could be therapeutic targets of breast
      cancer.

PMID- 29038732
TI  - Progressive sampling-based Bayesian optimization for efficient and automatic
      machine learning model selection.
AB  - PURPOSE: Machine learning is broadly used for clinical data analysis. Before
      training a model, a machine learning algorithm must be selected. Also, the values
      of one or more model parameters termed hyper-parameters must be set. Selecting
      algorithms and hyper-parameter values requires advanced machine learning
      knowledge and many labor-intensive manual iterations. To lower the bar to machine
      learning, miscellaneous automatic selection methods for algorithms and/or hyper
      parameter values have been proposed. Existing automatic selection methods are
      inefficient on large data sets. This poses a challenge for using machine learning
      in the clinical big data era. METHODS: To address the challenge, this paper
      presents progressive sampling-based Bayesian optimization, an efficient and
      automatic selection method for both algorithms and hyper-parameter values.
      RESULTS: We report an implementation of the method. We show that compared to a
      state of the art automatic selection method, our method can significantly reduce
      search time, classification error rate, and standard deviation of error rate due
      to randomization. CONCLUSIONS: This is major progress towards enabling fast
      turnaround in identifying high-quality solutions required by many machine
      learning-based clinical data analysis tasks.

PMID- 29038733
TI  - Mining comorbidity patterns using retrospective analysis of big collection of
      outpatient records.
AB  - BACKGROUND: Studying comorbidities of disorders is important for detection and
      prevention. For discovering frequent patterns of diseases we can use
      retrospective analysis of population data, by filtering events with common
      properties and similar significance. Most frequent pattern mining methods do not
      consider contextual information about extracted patterns. Further data mining
      developments might enable more efficient applications in specific tasks like
      comorbidities identification. METHODS: We propose a cascade data mining approach
      for frequent pattern mining enriched with context information, including a new
      algorithm MIxCO for maximal frequent patterns mining. Text mining tools extract
      entities from free text and deliver additional context attributes beyond the
      structured information about the patients. RESULTS: The proposed approach was
      tested using pseudonymised reimbursement requests (outpatient records) submitted
      to the Bulgarian National Health Insurance Fund in 2010-2016 for more than 5
      million citizens yearly. Experiments were run on 3 data collections. Some known
      comorbidities of Schizophrenia, Hyperprolactinemia and Diabetes Mellitus Type 2
      are confirmed; novel hypotheses about stable comorbidities are generated. The
      evaluation shows that MIxCO is efficient for big dense datasets. CONCLUSION:
      Explicating maximal frequent itemsets enables to build hypotheses concerning the
      relationships between the exogeneous and endogeneous factors triggering the
      formation of these sets. MixCO will help to identify risk groups of patients with
      a predisposition to develop socially-significant disorders like diabetes. This
      will turn static archives like the Diabetes Register in Bulgaria to a powerful
      alerting and predictive framework.

PMID- 29038734
TI  - Dilemma in management: a patient with active systemic lupus erythematosus
      presenting with pulmonary cavitary lesion.
AB  - Pulmonary manifestations of systemic lupus erythematosus (SLE) include, but are
      not limited to, pneumonia, interstitial pneumonitis, atelectasis and pleural
      effusion. Cavitary lung lesions are rarely associated with SLE. We present herein
      the case of a female patient with SLE and lupus nephritis who presented to the
      hospital with respiratory failure, rash and arthralgias. She was found to have a
      cavitary lung lesion most concerning for infection. However, despite an extensive
      inpatient antibiotic course, her symptoms persisted. After a collaborative effort
      between the primary team, pulmonology, infectious disease and rheumatology, she
      was placed on systemic glucocorticoid therapy, which resolved not only her
      respiratory failure, but also her cavitary lung lesion on subsequent follow-up
      with imaging. The dilemma of management in such cases will be discussed in
      addition to a review of previously reported cases.

PMID- 29038735
TI  - Enrichment of milk with magnesium provides healthier and safer dairy products.
AB  - Biofilms on the surfaces of milk-processing equipment are often a major source of
      contamination of dairy products. Members of the genus Bacillus appear to be among
      the most commonly found bacteria in dairy farms and processing plants. Bacillus
      species may thrive in dairy farm equipment and in dairy products since they can
      form robust biofilms during growth within milk. We found that fortification of
      milk with magnesium mitigated biofilm formation by Bacillus species, and thus
      could notably reduce dairy product spoilage. We also show that the mode of action
      of Mg2+ ions is specific to inhibition of transcription of genes involved in
      biofilm formation. Our further findings indicate that in the presence of Mg2+
      bacterial cells are hypersensitive to the heat pasteurization applied during milk
      processing. Additionally, we demonstrated that enrichment of milk with magnesium
      improved technological properties of milk products such as soft cheeses. Finally,
      we report that there is a notable increase in the intestinal bioavailability
      potential of magnesium from supplemented milk compared with that from non
      supplemented milk.

PMID- 29038737
TI  - Significant Bradycardia in Critically Ill Patients Receiving Dexmedetomidine and
      Fentanyl.
AB  - PURPOSE: To report a case series of three patients who developed significant
      bradycardia while receiving the combination of dexmedetomidine and fentanyl for
      sedation and analgesia. MATERIALS AND METHODS: This is a case series of patients
      obtained from a mixed medical, surgical, and cardiac ICU in a community teaching
      hospital. Three intubated patients receiving fentanyl and dexmedetomidine
      infusion developed sudden bradycardia requiring intervention. In all three cases,
      adjustments to therapy were required. RESULTS: All three patients experienced
      significant bradycardia, with a heart rate less than 50 bpm, and one patient
      briefly developed asystole. In Case  1, the fentanyl infusion rate was reduced by
      67% and the dexmedetomidine infusion rate was reduced by 25%. In Case  2, the
      sedation was changed to midazolam, and in Case  3, both fentanyl and
      dexmedetomidine were discontinued. In all three cases, there were no further
      incidences of significant bradycardia following intervention. CONCLUSIONS:
      Fentanyl used in combination with dexmedetomidine can result in clinically
      significant bradycardia. Further study is warranted to identify risk factors and
      elucidate the mechanisms that result in life-threatening bradycardia.

PMID- 29038738
TI  - A Case of Infective Endocarditis and Spinal Epidural Abscess Caused by
      Streptococcus mitis Bacteremia.
AB  - A 57-year-old man presented with abdominal pain, hematemesis, and melena. He
      reported taking high-dose ibuprofen for back pain and drinking several 24-ounce
      beers daily. Examination was remarkable for icteric sclera, poor dentition,
      tachycardia, and crescendo-decrescendo murmur at right upper sternal border,
      radiating to the carotids. Labs revealed leukocytosis, anemia, thrombocytopenia,
      and elevated liver function tests and INR. Endoscopy demonstrated antral ulcers,
      duodenitis, and esophagitis. Blood cultures were obtained and broad-spectrum
      antibiotics started; cultures later grew Streptococcus mitis, and antibiotic
      coverage was narrowed. Transthoracic echocardiogram (TTE) demonstrated aortic
      stenosis and regurgitation, but no vegetation. Repeat blood cultures were
      negative; however, the patient developed neurological symptoms concerning for
      cauda equina syndrome, and MRI revealed epidural abscess. Emergent decompression
      could not be performed as the patient developed hematemesis and required
      intubation. Transesophageal echocardiogram (TEE), initially deferred due to
      friable esophageal mucosa, was performed and revealed small aortic valve
      vegetation. Poor oral hygiene was felt to be the probable source of the patient's
      S. mitis bacteremia, epidural abscess, and infective endocarditis. The patient's
      neurological symptoms resolved without intervention and remaining teeth were
      extracted. This case demonstrates that Streptococcus mitis can result in
      clinically significant bacteremia, particularly in immunocompromised patients,
      including chronic heavy alcohol users.

PMID- 29038736
TI  - Down but Not Out: The Consequences of Pretangle Tau in the Locus Coeruleus.
AB  - Degeneration of locus coeruleus (LC) is an underappreciated hallmark of
      Alzheimer's disease (AD). The LC is the main source of norepinephrine (NE) in the
      forebrain, and its degeneration is highly correlated with cognitive impairment
      and amyloid-beta (Abeta) and tangle pathology. Hyperphosphorylated tau in the LC
      is among the first detectable AD-like neuropathology in the brain, and while the
      LC/NE system impacts multiple aspects of AD (e.g., cognition, neuropathology, and
      neuroinflammation), the functional consequences of hyperphosphorylated tau
      accrual on LC neurons are not known. Recent evidence suggests that LC neurons
      accumulate aberrant tau species for decades before frank LC cell body
      degeneration occurs in AD, suggesting that a therapeutic window exists. In this
      review, we combine the literature on how pathogenic tau affects forebrain neurons
      with the known properties and degeneration patterns of LC neurons to synthesize
      hypotheses on hyperphosphorylated tau-induced dysfunction of LC neurons and the
      prion-like spread of pretangle tau from the LC to the forebrain. We also propose
      novel experiments using both in vitro and in vivo models to address the many
      questions surrounding the impact of hyperphosphorylated tau on LC neurons in AD
      and its role in disease progression.

PMID- 29038739
TI  - Unusual Case of Superior Vena Cava Syndrome Caused by Intravascular Thyroid
      Metastasis.
AB  - Superior cava venous obstruction use to show a typical clinical presentation and
      a CT scan or even an ultrasonography can be sufficient to achieve an accurate
      diagnosis, but in this case, to obtain the final diagnosis, a multimodal
      assessment is needed. This case report shows a multidisciplinary approach which
      helped diagnose a complicated case, where conventional diagnostic methods were
      not enough.

PMID- 29038740
TI  - Reverse Fosbury Flop Tear of the Rotator Cuff.
AB  - INTRODUCTION: "Fosbury flop" tear is an avulsion of the posterosuperior rotator
      cuff from the bone with reversal healing on its medial bursal-side. This case
      report describes a unique variant of Fosbury flop tear with a lesion of the
      musculotendinous junction that healed, for its tendon part, on the anterior
      humerus and coracoid process. CASE PRESENTATION: A 62-year-old man developed a
      posttraumatic painful shoulder with active loss of range of motion. Magnetic
      resonance arthrography demonstrated a lesion of the musculotendinous junction of
      the supraspinatus with healing of the tendon on the above-mentioned structures
      (reverse Fosbury flop). During arthroscopic evaluation, tendon repair was not
      possible and a debridement to avoid subacromial and anterior impingement
      associated with a tenotomy of the long head of the biceps were carried out. One
      year postoperatively, the patient had complete range of motion and was satisfied
      with the clinical results. DISCUSSION AND CONCLUSION: Different Fosbury flop
      tears exist. Radiologists and orthopedic surgeons should be aware of these tear
      patterns as failure to recognize them may lead to inadequate treatment.

PMID- 29038741
TI  - Ligament Augmentation and Reconstruction System Failures in Repair of Grade V
      Acromioclavicular Joint Dislocation.
AB  - The Ligament Augmentation and Reconstruction System(r) (LARS(r)) represents a
      popular synthetic anatomical reduction method for acromioclavicular joint
      dislocation by means of coracoclavicular ligament reconstruction. To our
      knowledge, no early failure has been documented in the literature. We present two
      unusual cases of LARS failure, one at four months after implant and the other at
      three weeks, without obvious causes, requiring re-do reconstruction, and discuss
      potential contributory factors.

PMID- 29038742
TI  - Methylene C(sp3)-H Arylation of Aliphatic Ketones Using a Transient Directing
      Group.
AB  - Palladium-catalyzed methylene beta-C(sp3)-H arylation of aliphatic ketones using
      a transient directing group is developed. The use of alpha-benzyl beta-alanine
      directing group that forms a six-membered chelation with palladium is crucial for
      promoting the methylene C(sp3)-H bond activation.

PMID- 29038743
TI  - Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney
      glomerular-capillary-wall function on a chip.
AB  - An in vitro model of the human kidney glomerulus - the major site of blood
      filtration - could facilitate drug discovery and illuminate kidney-disease
      mechanisms. Microfluidic organ-on-a-chip technology has been used to model the
      human proximal tubule, yet a kidney-glomerulus-on-a-chip has not been possible
      because of the lack of functional human podocytes - the cells that regulate
      selective permeability in the glomerulus. Here, we demonstrate an efficient (>
      90%) and chemically defined method for directing the differentiation of human
      induced pluripotent stem (hiPS) cells into podocytes that express markers of the
      mature phenotype (nephrin+, WT1+, podocin+, Pax2-) and that exhibit primary and
      secondary foot processes. We also show that the hiPS-cell-derived podocytes
      produce glomerular basement-membrane collagen and recapitulate the natural
      tissue/tissue interface of the glomerulus, as well as the differential clearance
      of albumin and inulin, when co-cultured with human glomerular endothelial cells
      in an organ-on-a-chip microfluidic device. The glomerulus-on-a-chip also mimics
      adriamycin-induced albuminuria and podocyte injury. This in vitro model of human
      glomerular function with mature human podocytes may facilitate drug development
      and personalized-medicine applications.

PMID- 29038744
TI  - Autophagy and Ferroptosis - What's the Connection?
AB  - PURPOSE OF REVIEW: Autophagy is a conserved intracellular degradation system and
      plays a dual role in cell death, depending on context and phase. Ferroptosis is a
      new form of regulated cell death that mainly depends on iron accumulation and
      lipid peroxidation. In this review, we summarize the processes of autophagy and
      ferroptosis and discuss their crosstalk mechanisms at the molecular level. RECENT
      FINDINGS: The original study shows that ferroptosis is morphologically,
      biochemically, and genetically distinct from autophagy and other types of cell
      death. However, recent studies demonstrate that activation of ferroptosis is
      indeed dependent on the induction of autophagy. Additionally, many ferroptosis
      regulators such as SLC7A11, GPX4, NRF2, p53, HSPB1, CISD1, FANCD2, and ACSL4 have
      been identified as potential regulators of autophagy. SUMMARY: This review not
      only highlights the importance of autophagy as an emerging mechanism of
      ferroptosis, but also raises new insights regarding regulated cell death.

PMID- 29038745
TI  - The Contractile Phenotype of Dermal Fetal Fibroblasts in Scarless Wound Healing.
AB  - PURPOSE OF REVIEW: Injured skin in the mammalian fetus can heal regeneratively
      due to the ability of fetal fibroblasts to effectively reorganize the
      extracellular matrix (ECM). This process occurs without fetal fibroblasts
      differentiating into highly contractile myofibroblasts which cause scarring and
      fibrosis in adult wounds. Here, we provide a brief review of fetal wound healing
      and the evidence supporting a unique contractile phenotype in fetal fibroblasts.
      Furthermore, we discuss the biomechanical role of the ECM in driving
      myofibroblast differentiation in wound healing and the implications for new
      clinical modalities based on the biophysical properties of fetal fibroblasts.
      RECENT FINDINGS: We and others have found that fetal fibroblasts are refractory
      to the environmental stimuli necessary for myofibroblast differentiation in adult
      wound healing including mechanical stress. SUMMARY: Understanding the
      biomechanical mechanisms that regulate the contractile phenotype of fetal
      fibroblasts may unlock new avenues for anti-scarring therapies that target
      myofibroblast differentiation of adult fibroblasts.

PMID- 29038746
TI  - Influence of exercise duration on cardiorespiratory responses, energy cost and
      tissue oxygenation within a 6 hour treadmill run.
AB  - PURPOSE: The physiological mechanisms for alterations in oxygen utilization
      ([Formula: see text]) and the energy cost of running (Cr ) during prolonged
      running are not completely understood, and could be linked with alterations in
      muscle and cerebral tissue oxygenation. METHODS: Eight trained ultramarathon
      runners (three women; mean +/- SD; age 37 +/- 7 yr; maximum [Formula: see text]
      60 +/- 15 mL min-1 kg-1) completed a 6 hr treadmill run (6TR), which consisted of
      four modules, including periods of moderate (3 min at 10 km h-1, 10-CR) and heavy
      exercise intensities (6 min at 70% of maximum [Formula: see text], HILL),
      separated by three, 100 min periods of self-paced running (SP). We measured
      [Formula: see text], minute ventilation ([Formula: see text]), ventilatory
      efficiency ([Formula: see text]), respiratory exchange ratio (RER), Cr , muscle
      and cerebral tissue saturation index (TSI) during the modules, and heart rate
      (HR) and perceived exertion (RPE) during the modules and SP. RESULTS:
      Participants ran 58.3 +/- 10.5 km during 6TR. Speed decreased and HR and RPE
      increased during SP. Across the modules, HR and [Formula: see text] increased (10
      CR), and RER decreased (10-CR and HILL). There were no significant changes in
      [Formula: see text], [Formula: see text], Cr , TSI and RPE across the modules.
      CONCLUSIONS: In the context of positive pacing (decreasing speed), increased
      cardiac drift and perceived exertion over the 6TR, we observed increased RER and
      increased HR at moderate and heavy exercise intensity, increased [Formula: see
      text] at moderate intensity, and no effect of exercise duration on ventilatory
      efficiency, energy cost of running and tissue oxygenation.

PMID- 29038747
TI  - Light induced intraspecific variability in response to thermal stress in the hard
      coral Stylophora pistillata.
AB  - Recent research suggests that prior exposure of several months to elevated
      irradiance induces enhanced thermal tolerance in scleractinian corals. While this
      tolerance has been reported at the species level, individual coral colonies may
      react differently due to individual variability in thermal tolerance. As thermal
      anomalies are predicted to become common in the upcoming future, intraspecific
      variation may be key to the survival of coral populations. In order to study
      light-history based thermal stress responses on individual colonies, we developed
      a preliminary microcosm experiment where three randomly chosen, aquacultured
      colonies of the model coral Stylophora pistillata were exposed to two irradiance
      treatments (200 and 400 MUmol photons m-2 s-1) for 31 days, followed by
      artificially induced heat stress (~33.4  degrees C). We found different responses
      to occur at both the intraspecific and the intracolonial levels, as indicated by
      either equal, less severe, delayed, and/or even non-necrotic responses of corals
      previously exposed to the irradiance of 400 compared to 200 MUmol photons m-2 s
      1. In addition, all individual colonies revealed light-enhanced calcification.
      Finally, elevated irradiance resulted in a lower chlorophyll a concentration in
      one colony compared to the control treatment, and the same colony displayed more
      rapid bleaching compared to the other ones. Taken together, this study highlights
      the potential importance of intra-individual variability in physiological
      responses of scleractinian corals and provides recommendations for improving
      methodological designs for future studies.

PMID- 29038749
TI  - Extending SEQenv: a taxa-centric approach to environmental annotations of 16S
      rDNA sequences.
AB  - Understanding how the environment selects a given taxon and the diversity
      patterns that emerge as a result of environmental filtering can dramatically
      improve our ability to analyse any environment in depth as well as advancing our
      knowledge on how the response of different taxa can impact each other and
      ecosystem functions. Most of the work investigating microbial biogeography has
      been site-specific, and logical environmental factors, rather than geographical
      location, may be more influential on microbial diversity. SEQenv, a novel
      pipeline aiming to provide environmental annotations of sequences emerged to
      provide a consistent description of the environmental niches using the ENVO
      ontology. While the pipeline provides a list of environmental terms on the basis
      of sample datasets and, therefore, the annotations obtained are at the dataset
      level, it lacks a taxa centric approach to environmental annotation. The work
      here describes an extension developed to enhance the SEQenv pipeline, which
      provided the means to directly generate environmental annotations for taxa under
      different contexts. 16S rDNA amplicon datasets belonging to distinct biomes were
      selected to illustrate the applicability of the extended SEQenv pipeline. A
      literature survey of the results demonstrates the immense importance of sequence
      level environmental annotations by illustrating the distribution of both taxa
      across environments as well as the various environmental sources of a specific
      taxon. Significantly enhancing the SEQenv pipeline in the process, this
      information would be valuable to any biologist seeking to understand the various
      taxa present in the habitat and the environment they originated from, enabling a
      more thorough analysis of which lineages are abundant in certain habitats and the
      recovery of patterns in taxon distribution across different habitats and
      environmental gradients.

PMID- 29038748
TI  - Virulence test using nematodes to prescreen Nocardia species capable of inducing
      neurodegeneration and behavioral disorders.
AB  - BACKGROUND: Parkinson's disease (PD) is a disorder characterized by dopaminergic
      neuron programmed cell death. The etiology of PD remains uncertain-some cases are
      due to selected genes associated with familial heredity, others are due to
      environmental exposure to toxic components, but over 90% of cases have a sporadic
      origin. Nocardia are Actinobacteria that can cause human diseases like
      nocardiosis. This illness can lead to lung infection or central nervous system
      (CNS) invasion in both immunocompromised and immunocompetent individuals. The
      main species involved in CNS are N. farcinica, N. nova, N. brasiliensis and N.
      cyriacigeorgica. Some studies have highlighted the ability of N. cyriacigeorgica
      to induce Parkinson's disease-like symptoms in animals. Actinobacteria are known
      to produce a large variety of secondary metabolites, some of which can be
      neurotoxic. We hypothesized that neurotoxic secondary metabolite production and
      the onset of PD-like symptoms in animals could be linked. METHODS: Here we used a
      method to screen bacteria that could induce dopaminergic neurodegeneration before
      performing mouse experiments. RESULTS: The nematode Caenorhabditis elegans
      allowed us to demonstrate that Nocardia strains belonging to N. cyriacigeorgica
      and N. farcinica species can induce dopaminergic neurodegeneration. Strains of
      interest involved with the nematodes in neurodegenerative disorders were then
      injected in mice. Infected mice had behavioral disorders that may be related to
      neuronal damage, thus confirming the ability of Nocardia strains to induce
      neurodegeneration. These behavioral disorders were induced by N. cyriacigeorgica
      species (N. cyriacigeorgica GUH-2 and N. cyriacigeorgica 44484) and N. farcinica
      10152. DISCUSSION: We conclude that C. elegans is a good model for detecting
      Nocardia strains involved in neurodegeneration. This model allowed us to detect
      bacteria with high neurodegenerative effects and which should be studied in mice
      to characterize the induced behavioral disorders and bacterial dissemination.

PMID- 29038750
TI  - Is geography an accurate predictor of evolutionary history in the millipede
      family Xystodesmidae?
AB  - For the past several centuries, millipede taxonomists have used the morphology of
      male copulatory structures (modified legs called gonopods), which are strongly
      variable and suggestive of species-level differences, as a source to understand
      taxon relationships. Millipedes in the family Xystodesmidae are blind, dispersal
      limited and have narrow habitat requirements. Therefore, geographical proximity
      may instead be a better predictor of evolutionary relationship than morphology,
      especially since gonopodal anatomy is extremely divergent and similarities may be
      masked by evolutionary convergence. Here we provide a phylogenetics-based test of
      the power of morphological versus geographical character sets for resolving
      phylogenetic relationships in xystodesmid millipedes. Molecular data from 90
      species-group taxa in the family were included in a six-gene phylogenetic
      analysis to provide the basis for comparing trees generated from these
      alternative character sets. The molecular phylogeny was compared to topologies
      representing three hypotheses: (1) a prior classification formulated using
      morphological and geographical data, (2) hierarchical groupings derived from
      Euclidean geographical distance, and (3) one based solely on morphological data.
      Euclidean geographical distance was not found to be a better predictor of
      evolutionary relationship than the prior classification, the latter of which was
      the most similar to the molecular topology. However, all three of the alternative
      topologies were highly divergent (Bayes factor >10) from the molecular topology,
      with the tree inferred exclusively from morphology being the most divergent. The
      results of this analysis show that a high degree of morphological convergence
      from substantial gonopod shape divergence generated spurious phylogenetic
      relationships. These results indicate the impact that a high degree of
      morphological homoplasy may have had on prior treatments of the family. Using the
      results of our phylogenetic analysis, we make several changes to the
      classification of the family, including transferring the rare state-threatened
      species Sigmoria whiteheadi Shelley, 1986 to the genus Apheloria Chamberlin, 1921
      a relationship not readily apparent based on morphology alone. We show that while
      gonopod differences are a premier source of taxonomic characters to diagnose
      species pairwise, the traits should be viewed critically as taxonomic features
      uniting higher levels.

PMID- 29038751
TI  - Combining graph and flux-based structures to decipher phenotypic essential
      metabolites within metabolic networks.
AB  - BACKGROUND: The emergence of functions in biological systems is a long-standing
      issue that can now be addressed at the cell level with the emergence of high
      throughput technologies for genome sequencing and phenotyping. The reconstruction
      of complete metabolic networks for various organisms is a key outcome of the
      analysis of these data, giving access to a global view of cell functioning. The
      analysis of metabolic networks may be carried out by simply considering the
      architecture of the reaction network or by taking into account the stoichiometry
      of reactions. In both approaches, this analysis is generally centered on the
      outcome of the network and considers all metabolic compounds to be equivalent in
      this respect. As in the case of genes and reactions, about which the concept of
      essentiality has been developed, it seems, however, that some metabolites play
      crucial roles in system responses, due to the cell structure or the internal
      wiring of the metabolic network. RESULTS: We propose a classification of
      metabolic compounds according to their capacity to influence the activation of
      targeted functions (generally the growth phenotype) in a cell. We generalize the
      concept of essentiality to metabolites and introduce the concept of the
      phenotypic essential metabolite (PEM) which influences the growth phenotype
      according to sustainability, producibility or optimal-efficiency criteria. We
      have developed and made available a tool, Conquests, which implements a method
      combining graph-based and flux-based analysis, two approaches that are usually
      considered separately. The identification of PEMs is made effective by using a
      logical programming approach. CONCLUSION: The exhaustive study of phenotypic
      essential metabolites in six genome-scale metabolic models suggests that the
      combination and the comparison of graph, stoichiometry and optimal flux-based
      criteria allows some features of the metabolic network functionality to be
      deciphered by focusing on a small number of compounds. By considering the best
      combination of both graph-based and flux-based techniques, the Conquests python
      package advocates for a broader use of these compounds both to facilitate network
      curation and to promote a precise understanding of metabolic phenotype.

PMID- 29038752
TI  - Seasonal and year-round use of the Kushiro Wetland, Hokkaido, Japan by sika deer
      (Cervus nippon yesoensis).
AB  - The sika deer (Cervus nippon yesoensis) population in the Ramsar-listed Kushiro
      Wetland has increased in recent years, and the Ministry of the Environment of
      Japan has decided to take measures to reduce the impact of deer on the ecosystem.
      However, seasonal movement patterns of the deer (i.e., when and where the deer
      inhabit the wetland) remain unclear. We examined the seasonal movement patterns
      of sika deer in the Kushiro Wetland from 2013 to 2015 by analyzing GPS location
      data for 28 hinds captured at three sites in the wetland. Seasonal movement
      patterns were quantitatively classified as seasonal migration, mixed, dispersal,
      nomadic, resident, or atypical, and the degree of wetland utilization for each
      individual was estimated. The area of overlap for each individual among intra
      capture sites and inter-capture sites was calculated for the entire year and for
      each season. Our results showed that the movement patterns of these deer were
      classified not only as resident but also as seasonal migration, dispersal, and
      atypical. Approximately one-third of the individuals moved into and out of the
      wetland during the year as either seasonal migrants or individuals with atypical
      movement. Some of the individuals migrated to farmland areas outside the wetland
      (the farthest being 69.9 km away). Half of the individuals inhabited the wetland
      all or most of the year, i.e., 81-100% of their annual home range was within the
      wetland area. Even among individuals captured at the same site, different
      seasonal movement patterns were identified. The overlap areas of the home ranges
      of individuals from the same capture sites were larger than those for individuals
      from different capture sites (e.g., mean of annual home range overlap with intra
      capture sites: 47.7% vs. inter-sites: 1.3%). To achieve more effective ecosystem
      management including deer management in the wetland, management plans should
      cover inside and outside of the wetland and separate the population into multiple
      management units to address the different movement patterns and wetland
      utilization of the population.

PMID- 29038753
TI  - Infection of army ant pupae by two new parasitoid mites (Mesostigmata:
      Uropodina).
AB  - A great variety of parasites and parasitoids exploit ant societies. Among them
      are the Mesostigmata mites, a particularly common and diverse group of ant
      associated arthropods. While parasitism is ubiquitous in Mesostigmata,
      parasitoidism has only been described in the genus Macrodinychus. Yet information
      about the basic biology of most Macrodinychus species is lacking. Out of 24
      formally described species, information about basic life-history traits is only
      available for three species. Here we formally describe two new Macrodinychus
      species, i.e. Macrodinychus hilpertae and Macrodinychus derbyensis. In both
      species, immature stages developed as ecto-parasitoids on ant pupae of the South
      East Asian army ant Leptogenys distinguenda. By piercing the developing ant with
      their chelicera, the mites apparently suck ant hemolymph, ultimately killing host
      individuals. We compare infection rates among all studied Macrodinychus species
      and discuss possible host countermeasures against parasitoidism. The cryptic
      lifestyle of living inside ant nests has certainly hampered the scientific
      discovery of Macrodinychus mites and we expect that many more macrodinychid
      species await scientific discovery and description.

PMID- 29038754
TI  - Histamine-2 receptor antagonist famotidine modulates cardiac stem cell
      characteristics in hypertensive heart disease.
AB  - BACKGROUND: Cardiac stem cells (CSCs) play a vital role in cardiac homeostasis. A
      decrease in the efficiency of cardiac stem cells is speculated in various cardiac
      abnormalities. The maintenance of a healthy stem cell population is essential for
      the prevention of adverse cardiac remodeling leading to cardiac failure.
      Famotidine, a histamine-2 receptor antagonist, is currently used to treat ulcers
      of the stomach and intestines. In repurposing the use of the drug, reduction of
      cardiac hypertrophy and improvement in cardiac function of spontaneously
      hypertensive rats (SHR) was reported by our group. Given that stem cells are
      affected in cardiac pathologies, the effect of histamine-2 receptor antagonism on
      CSC characteristics was investigated. METHODS: To examine whether famotidine has
      a positive effect on CSCs, spontaneously hypertensive rats (SHR) treated with the
      drug were sacrificed; and CSCs isolated from atrial appendages was evaluated. Six
      month-old male SHRs were treated with famotidine (30 mg/kg/day) for two months.
      The effect of famotidine treatment on migration, proliferation and survival of
      CSCs was compared with untreated SHRs and normotensive Wistar rats. RESULTS:
      Functional efficiency of CSCs from SHR was compromised relative to that in Wistar
      rat. Famotidine increased the migration and proliferation potential, along with
      retention of stemness of CSCs in treated SHRs. Cellular senescence and oxidative
      stress were also reduced. The expression of H2R was unaffected by the treatment.
      DISCUSSION: As anticipated, CSCs from SHRs were functionally impaired. Stem cell
      attributes of famotidine-treated SHRs was comparable to that of Wistar rats.
      Therefore, in addition to being cardioprotective, the histamine 2 receptor
      antagonist modulated cardiac stem cells characteristics. Restoration of stem cell
      efficiency by famotidine is possibly mediated by reduction of oxidative stress as
      the expression of H2R was unaffected by the treatment. Maintenance of healthy
      stem cell population is suggested as a possible mechanism underlying the
      cardioprotective effect of famotidine.

PMID- 29038755
TI  - Evidence for continual hybridization rather than hybrid speciation between
      Ligularia duciformis and L. paradoxa (Asteraceae).
AB  - BACKGROUND: Hybrids possess phenotypic traits that are often intermediate between
      their parental taxa, which commonly serves as evidence of hybridization in
      morphological analyses. Natural hybridization has been shown to occur frequently
      in Ligularia (Asteraceae). In a previous study, Ligularia *maoniushanensis was
      demonstrated as a natural hybrid species between L. duciformis and L. paradoxa
      based on morphological and reproductive traits. METHODS: We used three
      chloroplast (cpDNA) fragments (psbA-trnH, trnL-rpl32 and trnQ-5'rps16), the
      nuclear ribosomal internal transcribed spacer (nrITS), and co-dominant SSR and
      dominant ISSR markers to study natural hybridization between L. duciformis and L.
      paradoxa growing sympatrically in two locations. Parental taxa were inferred
      using network analyses of cpDNA and nrITS haplotypes. Admixture among individuals
      was examined using the Bayesian clustering programs STRUCTURE and NewHybrids
      based on the SSR and ISSR data; and potential introgression in the SSR loci was
      assessed using the INTROGRESS package. RESULTS: The putative parental species
      were clearly distinguished from other sympatric Ligularia species by nrITS data,
      and L. *maoniushanensis individuals were confirmed to be the hybrid offspring of
      L. duciformis and L. paradoxa. Moreover, introgression was detected among several
      individuals morphologically identified as L. duciformis or L. paradoxa. Analyses
      of the cpDNA data revealed primarily unidirectional hybridization between L.
      duciformis and L. paradoxa, with L. paradoxa as the maternal parent in Mt.
      Maoniu, whereas bidirectional but asymmetrical hybridization was inferred to
      occur in Heihai Lake. The STRUCTURE analyses based on the SSR data detected two
      distinct clusters among the three taxa. The NewHybrids analyses showed that
      individuals circumscribed as L. *maoniushanensis were dominated by early- and
      later-generation and backcrossing hybrids. The NewHybrids results based on the
      ISSR data were congruent with SSR results. In addition, introgression was
      detected in some SSR loci, and heterogeneity among loci was found in terms of
      detected patterns of introgression. CONCLUSIONS: Our data provide strong evidence
      for hybridization and introgression between L. duciformis and L. paradoxa.
      Ligularia *maoniushanensis was demonstrated to be of hybrid origin. Since no
      evident reproductive isolation was found between the two parental species,
      detected hybrids appear to be part of hybrid swarms resulting from frequent and
      ongoing gene flow, which might impede the formation of a new hybrid species.

PMID- 29038756
TI  - The effects of familiarity on escape responses in the Trinidadian guppy (Poecilia
      reticulata).
AB  - Predation is the main cause of mortality during early life stages. The ability to
      avoid and evade potential threats is, therefore, favoured to evolve during the
      early stages of life. It is also during these early stages that the process of
      familiarization occurs. It has long been recognized that associating with
      familiar individuals confers antipredator benefits. Yet gaps in our knowledge
      remain about how predator evasion is affected by social experience during early
      stages. In this study, we test the hypothesis that familiarization acquired
      during early life stages improves escape responses. Using the guppy Poecilia
      reticulata, we examine the effect of different recent social conditions in the
      three main components of predator evasion. Using high-speed motion analysis, we
      compared the number of individuals in each test group that responded to a visual
      stimulus, their reactive distance and magnitude of their response (maximum speed,
      maximum acceleration and distance) in groups composed either of familiar or non
      familiar individuals. Contrary to the prediction, groups composed of familiar
      individuals were less responsive than groups of unfamiliar individuals. Reactive
      distance and magnitude of response were more dependent on individual size rather
      than on familiarity. Larger individuals reached higher maximum speeds and total
      distances in their escape response. Our result indicates that familiarity is
      likely to affect behaviour earlier in a predator-prey interaction, which then
      affects the behavioural component of the response. Taken together, our study
      contributes to previous ones by distinguishing which components of an escape
      response are modulated by familiarity.

PMID- 29038757
TI  - Complete mitochondrial genome sequences of the northern spotted owl (Strix
      occidentalis caurina) and the barred owl (Strix varia; Aves: Strigiformes:
      Strigidae) confirm the presence of a duplicated control region.
AB  - We report here the successful assembly of the complete mitochondrial genomes of
      the northern spotted owl (Strix occidentalis caurina) and the barred owl (S.
      varia). We utilized sequence data from two sequencing methodologies, Illumina
      paired-end sequence data with insert lengths ranging from approximately 250
      nucleotides (nt) to 9,600 nt and read lengths from 100-375 nt and Sanger-derived
      sequences. We employed multiple assemblers and alignment methods to generate the
      final assemblies. The circular genomes of S. o. caurina and S. varia are
      comprised of 19,948 nt and 18,975 nt, respectively. Both code for two rRNAs,
      twenty-two tRNAs, and thirteen polypeptides. They both have duplicated control
      region sequences with complex repeat structures. We were not able to assemble the
      control regions solely using Illumina paired-end sequence data. By fully spanning
      the control regions, Sanger-derived sequences enabled accurate and complete
      assembly of these mitochondrial genomes. These are the first complete
      mitochondrial genome sequences of owls (Aves: Strigiformes) possessing duplicated
      control regions. We searched the nuclear genome of S. o. caurina for copies of
      mitochondrial genes and found at least nine separate stretches of nuclear copies
      of gene sequences originating in the mitochondrial genome (Numts). The Numts
      ranged from 226-19,522 nt in length and included copies of all mitochondrial
      genes except tRNAPro , ND6, and tRNAGlu . Strix occidentalis caurina and S. varia
      exhibited an average of 10.74% (8.68% uncorrected p-distance) divergence across
      the non-tRNA mitochondrial genes.

PMID- 29038759
TI  - Nests of red wood ants (Formica rufa-group) are positively associated with
      tectonic faults: a double-blind test.
AB  - Ecological studies often are subjected to unintentional biases, suggesting that
      improved research designs for hypothesis testing should be used. Double-blind
      ecological studies are rare but necessary to minimize sampling biases and
      omission errors, and improve the reliability of research. We used a double-blind
      design to evaluate associations between nests of red wood ants (Formica rufa,
      RWA) and the distribution of tectonic faults. We randomly sampled two regions in
      western Denmark to map the spatial distribution of RWA nests. We then calculated
      nest proximity to the nearest active tectonic faults. Red wood ant nests were
      eight times more likely to be found within 60 m of known tectonic faults than
      were random points in the same region but without nests. This pattern paralleled
      the directionality of the fault system, with NNE-SSW faults having the strongest
      associations with RWA nests. The nest locations were collected without knowledge
      of the spatial distribution of active faults thus we are confident that the
      results are neither biased nor artefactual. This example highlights the benefits
      of double-blind designs in reducing sampling biases, testing controversial
      hypotheses, and increasing the reliability of the conclusions of research.

PMID- 29038758
TI  - Illegal use of natural resources in federal protected areas of the Brazilian
      Amazon.
AB  - BACKGROUND: The Brazilian Amazon is the world's largest rainforest regions and
      plays a key role in biodiversity conservation as well as climate adaptation and
      mitigation. The government has created a network of protected areas (PAs) to
      ensure long-term conservation of the region. However, despite the importance of
      and positive advances in the establishment of PAs, natural resource depletion in
      the Brazilian Amazon is pervasive. METHODS: We evaluated a total of 4,243
      official law enforcement records generated between 2010 and 2015 to understand
      the geographical distribution of the illegal use of resources in federal PAs in
      the Brazilian Amazon. We classified illegal activities into ten categories and
      used generalized additive models (GAMs) to evaluate the relationship between
      illegal use of natural resources inside PAs with management type, age of PAs,
      population density, and accessibility. RESULTS: We found 27 types of illegal use
      of natural resources that were grouped into 10 categories of illegal activities.
      Most infractions were related to suppression and degradation of vegetation
      (37.40%), followed by illegal fishing (27.30%) and hunting activities (18.20%).
      The explanatory power of the GAMs was low for all categories of illegal activity,
      with a maximum explained variation of 41.2% for illegal activities as a whole,
      and a minimum of 14.6% for hunting activities. DISCUSSION: These findings
      demonstrate that even though PAs are fundamental for nature conservation in the
      Brazilian Amazon, the pressures and threats posed by human activities include a
      broad range of illegal uses of natural resources. Population density up to 50 km
      from a PA is a key variable, influencing illegal activities. These threats
      endanger long-term conservation and many efforts are still needed to maintain PAs
      that are large enough and sufficiently intact to maintain ecosystem functions and
      protect biodiversity.

PMID- 29038760
TI  - Cellobiohydrolase B of Aspergillus niger over-expressed in Pichia pastoris
      stimulates hydrolysis of oil palm empty fruit bunches.
AB  - BACKGROUND: Aspergillus niger, along with many other lignocellulolytic fungi, has
      been widely used as a commercial workhorse for cellulase production. A fungal
      cellulase system generally includes three major classes of enzymes i.e., beta
      glucosidases, endoglucanases and cellobiohydrolases. Cellobiohydrolases (CBH) are
      vital to the degradation of crystalline cellulose present in lignocellulosic
      biomass. However, A. niger naturally secretes low levels of CBH. Hence,
      recombinant production of A. niger CBH is desirable to increase CBH production
      yield and also to allow biochemical characterisation of the recombinant CBH from
      A. niger. METHODS: In this study, the gene encoding a cellobiohydrolase B (cbhB)
      from A. niger ATCC 10574 was cloned and expressed in the methylotrophic yeast
      Pichia pastoris X-33. The recombinant CBHB was purified and characterised to
      study its biochemical and kinetic characteristics. To evaluate the potential of
      CBHB in assisting biomass conversion, CBHB was supplemented into a commercial
      cellulase preparation (Cellic(r) CTec2) and was used to hydrolyse oil palm empty
      fruit bunch (OPEFB), one of the most abundant lignocellulosic waste from the palm
      oil industry. To attain maximum saccharification, enzyme loadings were optimised
      by response surface methodology and the optimum point was validated
      experimentally. Hydrolysed OPEFB samples were analysed using attenuated total
      reflectance FTIR spectroscopy (ATR-FTIR) to screen for any compositional changes
      upon enzymatic treatment. RESULTS: Recombinant CBHB was over-expressed as a
      hyperglycosylated protein attached to N-glycans. CBHB was enzymatically active
      towards soluble substrates such as 4-methylumbelliferyl-beta-D-cellobioside
      (MUC), p-nitrophenyl-cellobioside (pNPC) and p-nitrophenyl-cellobiotrioside
      (pNPG3) but was not active towards crystalline substrates like Avicel(r) and
      Sigmacell cellulose. Characterisation of purified CBHB using MUC as the model
      substrate revealed that optimum catalysis occurred at 50  degrees C and pH 4 but
      the enzyme was stable between pH 3 to 10 and 30 to 80  degrees C. Although CBHB
      on its own was unable to digest crystalline substrates, supplementation of CBHB
      (0.37%) with Cellic(r) CTec2 (30%) increased saccharification of OPEFB by 27%.
      Compositional analyses of the treated OPEFB samples revealed that CBHB
      supplementation reduced peak intensities of both crystalline cellulose Ialpha and
      Ibeta in the treated OPEFB samples. DISCUSSION: Since CBHB alone was inactive
      against crystalline cellulose, these data suggested that it might work
      synergistically with other components of Cellic(r) CTec2. CBHB supplements were
      desirable as they further increased hydrolysis of OPEFB when the performance of
      Cellic(r) CTec2 was theoretically capped at an enzyme loading of 34% in this
      study. Hence, A. niger CBHB was identified as a potential supplementary enzyme
      for the enzymatic hydrolysis of OPEFB.

PMID- 29038761
TI  - Comparison of human papillomavirus (HPV) detection in urine and cervical swab
      samples using the HPV GenoArray Diagnostic assay.
AB  - Human papillomavirus (HPV) is the leading cause of cervical cancer. Urine-based
      HPV testing offers a simple and non-invasive method because of its increasing
      acceptance. A total of 164 pairs of cervical swab and urine samples from Thai
      women who underwent cervical cancer screening were used for HPV testing with HPV
      GenoArray Diagnostic Kits. The overall concordance percentage for HPV detection
      in the cervical swab and urine samples was 65.2%. The HPV genotypes most commonly
      detected were HPV16 and HPV18. An analysis of the urine samples and a second
      analysis of the cervical swab samples showed that the differences in the overall
      HPV detection rate between women with normal and abnormal cytology were not
      significant (p > 0.05). Urine samples processed with the GenoArray assay is an
      alternative for women who decline to undergo Pap smear even though it is not
      ideal as the first-line screening option.

PMID- 29038762
TI  - Clinical outcomes of residual or recurrent nasopharyngeal carcinoma treated with
      endoscopic nasopharyngectomy plus chemoradiotherapy or with chemoradiotherapy
      alone: a retrospective study.
AB  - BACKGROUND: Local residual and recurrent nasopharyngeal carcinoma (NPC) generally
      shows treatment failure after standard radiotherapy with or without concurrent
      chemotherapy. Whether endoscopic nasopharyngectomy might provide an additional
      therapeutic advantage remains controversial. Therefore, we retrospectively
      compared the clinical prognoses of patients with residual or recurrent NPC
      treated with endoscopic nasopharyngectomy combined with chemoradiotherapy (CRT)
      with those of patients treated with CRT alone. METHODS AND MATERIALS: A total of
      sixty-two patients with local residual or recurrent NPC were studied
      retrospectively: 36 patients received endoscopic nasopharyngectomy combined with
      CRT, whereas 26 patients who refused the surgery or had surgical
      contraindications received CRT alone. Serum Epstein-Barr virus (EBV) DNA levels
      were measured pre- and post-treatment. The differences in prognosis between the
      two treatment regimens and the pre- and post-treatment changes in EBV-DNA levels
      were analyzed. RESULTS: The median follow-up time was 31 months, with a 3-year
      overall survival (OS) of 51.40% and a 3-year disease-free survival (DFS) of
      46.86%. The surgery + CRT group had a better OS than the CRT alone group did
      (chi2 = 4.054, P = 0.044). The pretreatment EBV-DNA levels showed a positive
      correlation with the clinical staging of recurrent NPC (chi2 = 11.674, P =
      0.009). Patients with negative pretreatment serum EBV-DNA levels showed a
      superior OS to those of patients who tested positive for EBV-DNA (>0 copy/mL)
      (chi2 = 9.833, P = 0.002). The post-treatment EBV-DNA levels, compared with the
      pretreatment levels, decreased significantly in the surgery + CRT group (Z =  -
      3.484, P = 0.000). In contrast, the EBV-DNA levels after CRT alone did not
      decrease significantly (Z =  - 1.956, P = 0.051). Multivariate analysis indicated
      that local staging, pretreatment EBV-DNA load, and the treatment method were
      independent risk factors for OS. Subgroup analysis indicated that the patients
      who tested negative for EBV-DNA before the treatment and those who received
      surgery + CRT showed a better OS than those who received CRT alone. CONCLUSIONS:
      The pretreatment serum EBV-DNA level was associated with disease prognosis. The
      combination therapy preceded by surgery can effectively decrease the copy number
      of EBV-DNA. Patients with local intermediate- and late-stage NPC, especially
      those negative for EBV-DNA, may consider opting for surgery followed by post
      operative adjuvant radiotherapy or chemotherapy.

PMID- 29038763
TI  - Mouse spermatozoa with higher fertilization rates have thinner nuclei.
AB  - BACKGROUND: Although spermatozoa with normal morphology are assumed to have
      uniform fertilization ability, recent data show that even normal spermatozoa have
      considerable variation in their head shape which is associated with differences
      in fertilization ability. Appropriate quantitative indicators for good sperm
      morphology, however, remain unidentified. METHODS: Therefore, in an effort to
      identify such an indicator, we compared the nuclear contour of normal mouse
      spermatozoa by quantitative multivariate analysis using elliptic Fourier
      descriptors combined with principal component analysis. The spermatozoa were
      obtained from different strains and collection sites which have been shown to be
      associated with different fertilization abilities. RESULTS: We found that the
      head was 5.7% thinner in spermatozoa from the B6D2F1 (BDF1) strain, known to have
      a higher fertilization rate, than in those from the C57BL/6N (B6N) strain, which
      has a lower fertilization rate. Moreover, zona-penetrated spermatozoa in the
      perivitelline space consistently had 5.4% thinner heads than those isolated from
      the epididymis before ejaculation. The aspect ratio, which represents the sperm
      head thinness, uniquely distinguished these sperm populations, confirming its
      validity as a morphological indicator. DISCUSSION: Because aspect ratio has also
      been shown to characterize human spermatozoa, this unique morphometric indicator
      might be applicable to compare normal spermatozoa among multiple patients, which
      will greatly facilitate and enhance current reproductive technologies.

PMID- 29038764
TI  - Pulmonary transcriptomic responses indicate a dual role of inflammation in
      pneumonia development and viral clearance during 2009 pandemic influenza
      infection.
AB  - BACKGROUND: The interaction between influenza virus and the host response to
      infection clearly plays an important role in determining the outcome of
      infection. While much is known on the participation of inflammation on the
      pathogenesis of severe A (H1N1) pandemic 09-influenza virus, its role in the
      course of non-fatal pneumonia has not been fully addressed. METHODS: A systems
      biology approach was used to define gene expression profiles, histology and viral
      dynamics in the lungs of healthy immune-competent mice with pneumonia caused by a
      human influenza A (H1N1) pdm09 virus, which successfully resolved the infection.
      RESULTS: Viral infection activated a marked pro-inflammatory response at the lung
      level paralleling the emergence of histological changes. Cellular immune response
      and cytokine signaling were the two signaling pathway categories more
      representative of our analysis. This transcriptome response was associated to
      viral clearance, and its resolution was accompanied by resolution of
      histopathology. DISCUSSION: These findings suggest a dual role of pulmonary
      inflammation in viral clearance and development of pneumonia during non-fatal
      infection caused by the 2009 pandemic influenza virus. Understanding the dynamics
      of the host's transcriptomic and virological changes over the course of the
      infection caused by A (H1N1) pdm09 virus may help identifying the immune response
      profiles associated with an effective response against influenza virus.

PMID- 29038765
TI  - The complete chloroplast genome sequence of strawberry (Fragaria  * ananassa
      Duch.) and comparison with related species of Rosaceae.
AB  - Compared with other members of the family Rosaceae, the chloroplast genomes of
      Fragaria species exhibit low variation, and this situation has limited
      phylogenetic analyses; thus, complete chloroplast genome sequencing of Fragaria
      species is needed. In this study, we sequenced the complete chloroplast genome of
      F. * ananassa 'Benihoppe' using the Illumina HiSeq 2500-PE150 platform and then
      performed a combination of de novo assembly and reference-guided mapping of
      contigs to generate complete chloroplast genome sequences. The chloroplast genome
      exhibits a typical quadripartite structure with a pair of inverted repeats (IRs,
      25,936 bp) separated by large (LSC, 85,531 bp) and small (SSC, 18,146 bp) single
      copy (SC) regions. The length of the F. * ananassa 'Benihoppe' chloroplast genome
      is 155,549 bp, representing the smallest Fragaria chloroplast genome observed to
      date. The genome encodes 112 unique genes, comprising 78 protein-coding genes, 30
      tRNA genes and four rRNA genes. Comparative analysis of the overall nucleotide
      sequence identity among ten complete chloroplast genomes confirmed that for both
      coding and non-coding regions in Rosaceae, SC regions exhibit higher sequence
      variation than IRs. The Ka/Ks ratio of most genes was less than 1, suggesting
      that most genes are under purifying selection. Moreover, the mVISTA results also
      showed a high degree of conservation in genome structure, gene order and gene
      content in Fragaria, particularly among three octoploid strawberries which were
      F. * ananassa 'Benihoppe', F. chiloensis (GP33) and F. virginiana (O477).
      However, when the sequences of the coding and non-coding regions of F. * ananassa
      'Benihoppe' were compared in detail with those of F. chiloensis (GP33) and F.
      virginiana (O477), a number of SNPs and InDels were revealed by MEGA 7. Six non
      coding regions (trnK-matK, trnS-trnG, atpF-atpH, trnC-petN, trnT-psbD and trnP
      psaJ) with a percentage of variable sites greater than 1% and no less than five
      parsimony-informative sites were identified and may be useful for phylogenetic
      analysis of the genus Fragaria.

PMID- 29038766
TI  - External validation of cut-off points for foveal thickness taking into account
      the intraretinal fluid using optical coherence tomography to diagnose diabetic
      macular oedema.
AB  - BACKGROUND: In late 2015, cut-off points were published for foveal thickness to
      diagnose diabetic macular oedema taking into account the presence of intraretinal
      fluid using optical coherence tomography (OCT) in primary care patients (90 um in
      the presence of intraretinal fluid and 310 um otherwise). METHODS: This cross
      sectional observational study was carried out on 134 eyes of diabetic patients
      treated in specialised ophthalmology services in a Spanish region in 2012-2013,
      to externally validate the aforementioned cut-off points. The main variable
      (Clinical Standard) was the diagnosis of macular oedema through indirect
      ophthalmoscopy and posterior segment slit-lamp biomicroscopy. As validation
      variables, both the foveal thickness and the presence of intraretinal fluid
      obtained by OCT were used. Validation was performed using bootstrapping by
      calculating the area under the ROC curve (AUC), sensitivity, specificity,
      positive likelihood ratio (PLR) and negative likelihood ratio (NLR). RESULTS:
      Forty-one eyes presented diabetic macular oedema (30.6%). The bootstrapping
      validation parameters were: AUC, 0.88; sensitivity, 0.75; specificity, 0.95; PLR,
      14.31; NLR, 0.26. These values were very similar to those of the original
      publication. CONCLUSION: We have externally validated in specialised care
      patients the cut-off points published for the diagnosis of diabetic macular
      oedema. We suggest that others carry out validation studies in their communities.

PMID- 29038768
TI  - Gut microbial metabolite short-chain fatty acids and obesity.
AB  - Over the past decade, the gut microbiota has emerged as an essential mediator in
      the pathophysiology of obesity and related metabolic disorders. In this context,
      the reciprocal interactions of the gut microbiota structure and their metabolite
      profiles with host metabolism predisposing to a range of pathological conditions
      (e.g., insulin resistance) related to energy homeostasis have been increasingly
      discussed in various animal models and human cohorts. Remarkably, as the role of
      gut microbial metabolites as critical signaling molecules that function through
      the complementary host receptors has come to be appreciated, tremendous attention
      has been focused on the proposed diet-gut microbiota-host homeostasis axis,
      entailing extensive cross-disciplinary efforts in medical, pharmaceutical, and
      agricultural sciences. This review will discuss the recent advances in
      understanding the mechanisms whereby the gut microbiota modulates the effects of
      diet and shapes the host metabolism either towards or away from obesity and
      related metabolic conditions. In particular, the interactions of short chain
      fatty acids (SCFAs), a subset of key gut microbial metabolites, with their
      specific receptors will be reviewed in relation to host energy homeostatic
      regulation and evaluated for potential as novel therapeutic targets for diet
      induced obesity.

PMID- 29038767
TI  - Evaluation of plasma cytokines in patients with cocaine use disorders in
      abstinence identifies transforming growth factor alpha (TGFalpha) as a potential
      biomarker of consumption and dual diagnosis.
AB  - BACKGROUND: Cocaine use disorder (CUD) is a complex health condition, especially
      when it is accompanied by comorbid psychiatric disorders (dual diagnosis). Dual
      diagnosis is associated with difficulties in the stratification and treatment of
      patients. One of the major challenges in clinical practice of addiction
      psychiatry is the lack of objective biological markers that indicate the degree
      of consumption, severity of addiction, level of toxicity and response to
      treatment in patients with CUD. These potential biomarkers would be fundamental
      players in the diagnosis, stratification, prognosis and therapeutic orientation
      in addiction. Due to growing evidence of the involvement of the immune system in
      addiction and psychiatric disorders, we tested the hypothesis that patients with
      CUD in abstinence might have altered circulating levels of signaling proteins
      related to systemic inflammation. METHODS: The study was designed as a cross
      sectional study of CUD treatment-seeking patients. These patients were recruited
      from outpatient programs in the province of Malaga (Spain). The study was
      performed with a total of 160 white Caucasian subjects, who were divided into the
      following groups: patients diagnosed with CUD in abstinence (N = 79, cocaine
      group) and matched control subjects (N = 81, control group). Participants were
      clinically evaluated with the diagnostic interview PRISM according to the DSM-IV
      TR, and blood samples were collected for the determination of chemokine C-C motif
      ligand 11 (CCL11, eotaxin-1), interferon gamma (IFNgamma), interleukin-4 (IL-4),
      interleukin-8 (IL-8), interleukin-17alpha (IL-17alpha), macrophage inflammatory
      protein 1alpha (MIP-1alpha) and transforming growth factor alpha (TGFalpha)
      levels in the plasma. Clinical and biochemical data were analyzed in order to
      find relationships between variables. RESULTS: While 57% of patients with CUD
      were diagnosed with dual diagnosis, approximately 73% of patients had other
      substance use disorders. Cocaine patients displayed greater cocaine symptom
      severity when they were diagnosed with psychiatric comorbidity. Regarding
      inflammatory factors, we observed significantly lower plasma levels of IL-17alpha
      (p < 0.001), MIP-1alpha (p < 0.001) and TGFalpha (p < 0.05) in the cocaine group
      compared with the levels in the control group. Finally, there was a significant
      primary effect of dual diagnosis on the plasma concentrations of TGFalpha (p <
      0.05) in the cocaine group, and these levels were lower in patients with dual
      diagnoses. DISCUSSION: IL-17alpha, MIP-1alpha and TGFalpha levels are different
      between the cocaine and control groups, and TGFalpha levels facilitate the
      identification of patients with dual diagnosis. Because TGFalpha reduction is
      associated with enhanced responses to cocaine in preclinical models, we propose
      TGFalpha as a potential biomarker of complex CUD in humans.

PMID- 29038770
TI  - Lactobacillus apinorum belongs to the fructophilic lactic acid bacteria.
AB  - Potential fructophilic characteristics of Lactobacillus apinorum, originally
      isolated from the guts of honeybees (Apis mellifera), were studied in the present
      study. The species showed typical fructophilic growth characteristics, i.e.,
      active growth on d-fructose, poor growth on d-glucose, and accelerated growth on
      d-glucose in the presence of electron acceptors. Biochemical characteristics
      strongly supported classification of the species into fructophilic lactic acid
      bacteria (FLAB). Furthermore, genetic analyses suggested that the species
      underwent extensive gene reduction, similar to that recorded for Lactobacillus
      kunkeei and other FLAB. These data clearly indicated that L. apinorum is the
      second fructophilic species within the genus Lactobacillus.

PMID- 29038769
TI  - Polysaccharide from black currant (Ribes nigrum L.) stimulates dendritic cells
      through TLR4 signaling.
AB  - Black currant (Ribes nigrum) has various beneficial properties for human health.
      In particular, polysaccharide from black currant was found to be an
      immunostimulating food ingredient and was reported to have antitumor activity in
      a mouse model. We named it cassis polysaccharide (CAPS). In a previous study,
      CAPS administration caused tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta) production in vitro and in vivo, but the
      immunological mechanism of CAPS was not demonstrated. In this study, we revealed
      the CAPS immunostimulating mechanism in vitro. First, we found that CAPS
      activated dendritic cells (DCs). Second, we investigated whether it depends on
      Toll-like receptor 4 (TLR4) and myeloid differentiation primary response (Myd).
      We concluded that CAPS stimulates DCs through Myd88 depending TLR4 signaling and
      activates Th1-type cytokine release.

PMID- 29038771
TI  - Detection of antibiotic resistance genes in the feces of young adult Japanese.
AB  - Antibiotic resistance genes in the feces of healthy young adult Japanese were
      analyzed with polymerase chain reaction using specific primers. Antibiotic
      resistance genes against macrolides (ermB, ermF, ermX, and mefA/E), tetracyclines
      (tetW, tetQ, tetO, and tetX), beta-lactam antibiotics (blaTEM ), and streptomycin
      (aadE) were detected in more than 50% of subjects. These antibiotic resistance
      genes are likely widespread in the large intestinal bacteria of young adult
      Japanese.

PMID- 29038772
TI  - Revealing the genomic differences between two subgroups in Lactobacillus gasseri.
AB  - Being an autochthonous species in humans, Lactobacillus gasseri is widely used as
      a probiotic for fermented products. We thoroughly compared the gene contents of
      75 L. gasseri genomes and identified two intraspecific groups by the average
      nucleotide identity (ANI) threshold of 94%. Group I, with 48 strains, possessed
      53 group-specific genes including the gassericin T cluster (9 genes) and N-acyl
      homoserine lactone lactonase. Group II, with 27 strains, including the type
      strain ATCC 33323, possessed group-specific genes with plasmid- or phage-related
      annotations. The genomic differences provide evidences for demarcating a new
      probiotic group within L. gasseri.

PMID- 29038773
TI  - A fusion protein strategy for soluble expression of Stevia glycosyltransferase
      UGT76G1 in Escherichia coli.
AB  - The UDP-glucosyltransferase UGT76G1 from Stevia rebaudiana converts stevioside to
      rebaudioside A via a one-step glycosylation reaction, which increases the amount
      of sweet-tasting rebaudioside A and decreases the amount of stevioside that has a
      bitter aftertaste. This enzyme could, therefore, conceivably be used to improve
      the organoleptic properties of steviol glycosides and offer a cost-effective
      preparation of high-purity rebaudioside A. Producing soluble enzymes by
      overexpression is a prerequisite for large-scale biocatalysis. However, most of
      the UGT76G1 overexpressed in Escherichia coli is in inclusion bodies. In this
      study, three N-terminal fusion partners, 3'-phosphoadenosine-5'-phosphatase
      (CysQ), 2-keto-3-deoxy-6-phosphogluconate aldolase (EDA) and N-utilisation
      substance A (NusA), were tested to improve UGT76G1 expression and solubility in
      E. coli. Compared with the fusion-free protein, the solubility of UGT76G1 was
      increased 40% by fusion with CysQ, and the glucosyltransferase activity of the
      crude extract was increased 82%. This successful CysQ fusion strategy could be
      applied to enhance the expression and solubility of other plant-derived
      glucosyltransferases and presumably other unrelated proteins in the popular,
      convenient and cost-effective E. coli host.

PMID- 29038775
TI  - Intralesional Endoscopy and Septectomy as a Diagnostic Tool and Treatment Method
      for Lymphatic Malformations.

PMID- 29038774
TI  - Interaction of turmeric (Curcuma longa L.) with beneficial microbes: a review.
AB  - Curcuma longa L., commonly known as turmeric, is a rhizomatous herb of the family
      Zingiberaceae. It is mostly used as a spice, a coloring agent and broadly used in
      traditional medicine such as Ayurveda, Unani, etc., Turmeric rhizomes interact
      with a large numbers of rhizosphere-associated microbial species, and some enter
      the plant tissue and act as endophytes. Both rhizospheric and endophytic species
      are directly or indirectly involved in growth promotion and disease management in
      plants and also play an important role in the modulation of morphological growth,
      secondary metabolite production, curcumin content, antioxidant properties, etc.
      The present review focuses on the rhizobacterial and endophytic bacterial and
      fungal populations associated with the turmeric.

PMID- 29038776
TI  - Torsion of an Accessory Hepatic Lobe with Embedded Gallbladder: In an 11-Month
      Old Boy.
AB  - An accessory lobe of the liver is a rare entity in clinical practice which is
      diagnosed incidentally. Infrequently, it may present as torsion with a clinical
      picture of an acute abdomen, a palpable mass, and may be associated with liver
      function abnormalities. Many of these patients have a history of previous surgery
      for congenital abdominal wall defects such as omphalocele. We present an
      extremely rare case of torsion of an accessory hepatic lobe in an 11-month-old
      male patient who presented in a state of shock. The infant underwent laparotomy
      and excision of the accessory lobe. Here, we aim to emphasize the importance of
      prompt management and early resection which is the cornerstone of a favorable
      outcome.

PMID- 29038778
TI  - Ophthalmological abnormalities in wild European hedgehogs (Erinaceus europaeus):
      a survey of 300 animals.
AB  - In this study we aimed to examine wild European hedgehogs (Erinaceus europaeus)
      in rescue centres and to determine ocular abnormalities in this animal
      population. Three hundred animals varying in age from 2 months to 5 years were
      examined, 147 being male and 153 female. All animals were evaluated with direct
      and indirect ophthalmoscopy and slit lamp biomicroscopy in animals where lesions
      were detected. Tonometry using the Tonovet rebound tonometer was undertaken in
      selected animals as was assessment of tear production using the Schirmer I tear
      test. Four animals were affected by orbital infection, 3 were anophthalmic, 2
      unilaterally and one bilaterally, 3 by conjunctivitis, 3 by non-ulcerative
      keratitis and 4 by uveitis with corneal oedema. Fifty seven animals were affected
      by cataract, 54 with bilateral nuclear lens opacities. Twenty six of these
      animals were young animals considered too small to hibernate. This report
      documents the first prospective study of ocular disease in the European hedgehog.
      The predominant finding was bilateral nuclear cataract seen particularly in young
      poorly growing animals. Investigation into the potential causation of cataracts
      by poor nutrition or poor feeding ability by lens opacification requires further
      study.

PMID- 29038779
TI  - Tear ferning in normal dogs and dogs with keratoconjunctivitis sicca.
AB  - This study evaluates tear ferning as an ancillary technique for the evaluation of
      the canine tear film in normal eyes and eyes affected by keratoconjunctivitis
      sicca (KCS). Thirty dogs with KCS and 50 control dogs with normal tear film were
      evaluated with a full ophthalmoscopic examination and a Schirmer tear test type 1
      (STT) determined before tear samples were obtained from the medial canthus with a
      microhaematocrit capillary tube. 10ul of tear was placed on a microscope slide
      and the time to first formation of a fern of crystallised tear solute was
      determined. The appearance of the ferning pattern was graded and correlated with
      the STT value. All eyes with KCS had abnormal ferning patterns while 39 out of
      the 50 normal dogs (78%) had so-called 'normal' ferning patterns. The mean STT
      for dogs showing 'normal' ferning patterns was 20.6mm/min for the left eye and
      21.3mm/min for the right eye. STT values for eyes with 'abnormal' ferning
      patterns were 10.9mm/min and 12.4mm/min, these differing from the normal eyes
      with STT above 15mm/min significantly. These findings suggest that tear ferning
      could be a valuable technique for assessment of the tear film in dogs with KCS.

PMID- 29038780
TI  - Pulmonary ossification and microlithiasis in a bitch with multicentric mammary
      tumors.
AB  - Microliths and ossification were found in the lungs of a 12-year-old bitch
      suffering from compound mammary gland tumor which has disseminated in the
      inguinal lymph node glands and the lungs. Pulmonary ossification appeared grossly
      as irregular stony sharp particles which infiltrated the lung tissue and were
      readily recognizable from under the pleura as grayish sharp protruding particles.
      Microscopic examination revealed the existence of intra-alveolar single or
      multilobular particles of ossification which are formed of lamellated osseous
      substance with osteocytes in lacunae. Microlith particles were also seen and were
      smaller, usually solitary and less frequent. They comprised strongly basophilic
      smooth laminated spherical particles which may enclose faintly stained
      substances. Both structures were not associated with inflammatory response.
      Larger particles appeared as white miliary spots by radiography. This article
      documents for a very rare case of pulmonary microlithiasis and ossification in a
      dog.

PMID- 29038777
TI  - The ABCD study of neurodevelopment: Identifying neurocircuit targets for
      prevention and treatment of adolescent substance abuse.
AB  - Substance use disorders (SUD) can be considered developmental disorders in light
      of their frequent origins in substance initiation during adolescence. Cross
      sectional functional magnetic resonance imaging (fMRI) studies of adolescent
      substance users or adolescents with SUD have indicated aberrations in brain
      structures or circuits implicated in motivation, self-control, and mood
      regulation. However, attributing these differences to the neurotoxicological
      effects of chronic substance use has been problematic in that these circuits are
      also aberrant in at-risk children, such as those with prenatal substance
      exposure, externalizing disorders (such as conduct disorder), or prodromal
      internalizing disorders such as depression. To better isolate the effects of
      substance exposure on the adolescent brain, the newly-launched Adolescent Brain
      Cognitive Development (ABCD) study, funded by the National Institutes of Health,
      will follow the neurodevelopmental trajectories of over 11,000 American 9/10-year
      olds for 10 years, into emerging adulthood. This study will provide a rich open
      access dataset on longitudinal interactions of neurodevelopment, environmental
      exposures, and childhood psychopathology that confer addiction risk. The ABCD
      twin study will further clarify genetic versus experiential influences (e.g.,
      substance use) on neurodevelopmental and psychosocial outcomes. Neurocircuitry
      thought to regulate mood and behavior has been directly normalized by
      administration of psychoactive medications and by cognitive therapies in adults.
      Because of this, we contend that ABCD project data will be a crucial resource for
      prevention and treatment of SUD in adolescence because its cutting-edge
      neuroimaging and childhood assessments hold potential for discovery of additional
      targetable brain differences earlier in development that are prognostic of (or
      aberrant in) SUD. The ABCD sample size will also have the power to illuminate how
      sex differences, environmental interactions and other individual differences
      interact with neurodevelopment to inform treatment in different groups of
      adolescents.

PMID- 29038781
TI  - Comparison between fish and linseed oils administered orally for the treatment of
      experimentally induced keratoconjunctivitis sicca in rabbits.
AB  - The objective of this study was to compare the efficacy of two sources of omega 3
      and 6, fish oil (FO) and linseed oil (LO), orally administered, alone or in
      combination, for treating experimentally induced keratoconjunctivitis sicca (KCS)
      in rabbits. Twenty-eight New Zealand rabbits were used in this study. Seven
      animals were allocated to the C group (negative control), and KCS was induced in
      21 animals by topically applying 1% atropine sulfate drops for 7 days. Treatment
      with atropine was maintained throughout the study period (12 weeks). The rabbits
      were divided into 3 treatment groups containing 7 animals each: FO group, LO
      group and FLO group (FO and LO). The animals were evaluated using the Schirmer
      Tear Test I (STT I), Rose Bengal Test (RBT), fluorescein test (FT), tear film
      break-up time (TBUT), and conjunctival and histopathological analysis. There was
      a significant increase in STT I and TBUT values in treatment groups, but the
      increase occurred earlier in the FO group. The results of the RBT and FT were
      similar among treatment groups, except FT, in the FLO group, negative staining
      was only in 12 weeks. There was a significant decrease in the number of goblet
      cells in the FLO group compared with the other groups. The results demonstrated
      that orally administered of FO and LO improved the clinical signs of KCS.
      However, improvement occurred earlier in the FO group. Using oils in combination
      did not provide additional benefits. These results contribute to the future
      development of new oral formulations as adjuvant therapies for KCS.

PMID- 29038782
TI  - Jejuno-jejunal intussusception in a guinea pig (Cavia porcellus).
AB  - An approximately four-year-old male castrated guinea pig (Cavia porcellus) was
      presented for painful defecation with a 24-hour history of hyporexia and
      intermittent episodes of rolling behavior. Upon presentation the patient was
      quiet, alert, and responsive, and mildly hypothermic. Abdominal palpation
      revealed an approximately 2-cm long oblong mass within the caudal abdomen.
      Abdominal radiographs revealed gastric dilation without volvulus and a peritoneal
      mass effect. The patient was euthanized following gastric reflux of brown
      malodorous fluid from his nares and oral cavity. A necropsy was performed and
      revealed a jejuno-jejunal intussusception causing mechanical gastrointestinal
      ileus, and gastric dilatation without volvulus. While non-obstructive
      gastrointestinal stasis is common and obstructive ileus is uncommon in guinea
      pigs, this report shows that intestinal intussusception is a differential in
      guinea pigs with ileus and gastric dilatation.

PMID- 29038784
TI  - Epistemology of Natural Strategies for Cardiac Tissue Repair.

PMID- 29038783
TI  - Seroprevalence of Schmallenberg virus and other Simbu group viruses among the
      Lebanese sheep.
AB  - In order to evaluate for the first time, the serological prevalence of
      Schmallenberg virus (SBV) and other Simbu group viruses in Lebanon, sheep
      originating from 15 Lebanese regions were sampled in September 2016. A total
      number of 750 serum samples from Awassi sheep were tested by ELISA for viral
      nucleoprotein antibodies. From the sampled animals, 122 animals were seropositive
      to SBV/Simbu group viruses. The seropositive sheep were mainly located in South
      Lebanon. At herd level, a seroprevalence of 53.33% was recorded in the Seven
      Lebanese governorates, whereas the animal level seroprevalence was 16.26%. The
      seroprevalence was negative in Mount-Lebanon. Despite that there was some
      serological evidence showed the presence of some Simbu group viruses in the
      Middle East, no study was done in Lebanon. In this study, we report for the first
      time the prevalence of SBV and other Simbu group viruses in Lebanon.

PMID- 29038785
TI  - Biological Function of MicroRNA193a-3p in Health and Disease.
AB  - MicroRNAs (miRNAs) are a class of small noncoding RNAs that act mainly as
      negative regulators of gene expression. Several studies demonstrated that miRNAs
      take part in numerous biological processes, such as proliferation, apoptosis, and
      migration. The dysregulation of miRNAs has been frequently observed in different
      types of disease, including cancer. Here, we provide a comprehensive review on
      the human miR-193a-3p by considering its role in both physiological and
      pathological contexts. Different mechanisms involved in regulating miR-193a-3p
      expression have been reported, including epigenetic modifications and
      transcription factors. In physiological contexts, miR-193a-3p seemed able to
      limit proliferation and cell cycle progression in normal cells. Remarkably,
      several publications demonstrated that miR-193a-3p acted as a tumor suppressor
      miRNA in cancer by targeting different genes involved in proliferation,
      apoptosis, migration, invasion, and metastasis. Furthermore, the downregulation
      of miR-193a-3p has been observed in many primary tumors and altered levels of
      circulating miR-193a-3p have been identified in serum or plasma of cancer
      patients and subjects affected by Parkinson's disease or by schizophrenia. In a
      clinical perspective, further studies are needed to explore the antitumor effects
      of the miR-193a-3p mimics delivery and the relevance of this miRNA detection as a
      possible diagnostic and prognostic biomarker.

PMID- 29038787
TI  - Comparative Proteomic Analysis of Paulownia fortunei Response to Phytoplasma
      Infection with Dimethyl Sulfate Treatment.
AB  - Paulownia fortunei is a widely cultivated economic forest tree species that is
      susceptible to infection with phytoplasma, resulting in Paulownia witches' broom
      (PaWB) disease. Diseased P. fortunei is characterized by stunted growth, witches'
      broom, shortened internodes, and etiolated and smaller leaves. To understand the
      molecular mechanism of its pathogenesis, we applied isobaric tags for relative
      and absolute quantitation (iTRAQ) and liquid chromatography coupled with tandem
      mass spectrometry approaches to study changes in the proteomes of healthy P.
      fortunei, PaWB-infected P. fortunei, and PaWB-infected P. fortunei treated with
      15 mg.L-1 or 75 mg.L-1 dimethyl sulfate. We identified 2969 proteins and 104 and
      32 differentially abundant proteins that were phytoplasma infection responsive
      and dimethyl sulfate responsive, respectively. Based on our analysis of the
      different proteomes, 27 PaWB-related proteins were identified. The protein
      protein interactions of these 27 proteins were analyzed and classified into four
      groups (photosynthesis-related, energy-related, ribosome-related, and individual
      proteins). These PaWB-related proteins may help in developing a deeper
      understanding of how PaWB affects the morphological characteristics of P.
      fortunei and further establish the mechanisms involved in the response of P.
      fortunei to phytoplasma.

PMID- 29038786
TI  - MicroRNAs as Biomarkers in Thyroid Carcinoma.
AB  - Optimal management of patients with thyroid cancer requires the use of sensitive
      and specific biomarkers. For early diagnosis and effective follow-up, the
      currently available cytological and serum biomarkers, thyroglobulin and
      calcitonin, present severe limitations. Research on microRNA expression in
      thyroid tumors is providing new insights for the development of novel biomarkers
      that can be used to diagnose thyroid cancer and optimize its management. In this
      review, we will examine some of the methods commonly used to detect and quantify
      microRNA in biospecimens from patients with thyroid tumor, as well as the
      potential applications of these techniques for developing microRNA-based
      biomarkers for the diagnosis and prognostic evaluation of thyroid cancers.

PMID- 29038788
TI  - Urinary Exosomal MicroRNA Profiling in Incipient Type 2 Diabetic Kidney Disease.
AB  - BACKGROUND: Albuminuria is an early sign but not a strong predictor of diabetic
      kidney disease (DKD). Owing to their high stability, urinary exosomal miRNAs can
      be useful predictors of the progression of early-stage DKD to renal failure;
      fluid biopsies are ideal for detecting abnormalities in these miRNAs. The aim of
      this study was to identify novel differentially expressed miRNAs as urine
      biomarkers for type 2 DKD by comparing between patients of type 2 diabetes (T2D)
      with and without macroalbuminuria. METHODS: Ten patients with T2D, including five
      who had no renal disease and five with macroalbuminuria (DKD G1-2A3), were
      selected for this study. Exosome- (UExo-) derived miRNA profiles were used to
      identify candidate biomarkers, a subset of which was verified using quantitative
      reverse transcription PCR. RESULTS: A total of 496 UExo-derived miRNA species
      were found to be differentially expressed (>2-fold) in patients with DKD,
      compared to those with T2D. A validation analysis revealed that three miRNAs (miR
      362-3p, miR-877-3p, and miR-150-5p) were upregulated and one (miR-15a-5p) was
      downregulated. These miRNAs might regulate DKD through p53, mTOR, and AMPK
      pathways. CONCLUSIONS: In conclusion, UExo-derived miRNAs were altered in type 2
      DKD. MiR-362-3p, miR-877-3p, miR-150-5p, and miR-15a-5p might be novel biomarkers
      for incipient DKD.

PMID- 29038789
TI  - Diosgenin, a Novel Aldose Reductase Inhibitor, Attenuates the Galactosemic
      Cataract in Rats.
AB  - OBJECTIVE: To seek efficient aldose reductase inhibitors (ARIs) with excellent in
      vitro and in vivo biological activities against rat galactosemic cataract.
      METHODS: The method was firstly optimized to screen strong ARIs from nonoriented
      synthetic compounds and natural extracts. Then, diosgenin was assessed on osmotic
      expansion of primarily cultured lens epithelial cells (LECs) induced by galactose
      (50 mM). Diosgenin was administered to galactosemic rats by oral (100 and 200
      mg/kg) or direct drinking (0.1%) to evaluate its anticataract effects. RESULTS:
      Diosgenin was found as the strongest ARI with IC50 of 4.59 * 10-6 mol/L.
      Diosgenin (10 MUM) evidently inhibited the formation of tiny vacuoles and
      upregulation of AR mRNA in LECs. In vivo, diosgenin delayed lens opacification,
      inhibited the increase of ratio of lens weight to body weight, and decreased AR
      activity, galactitol level, and AR mRNA expression, especially in the diosgenin
      drinking (0.1%) group. CONCLUSIONS: Diosgenin was an efficient ARI, which not
      only significantly decreased the LECs' osmotic expansion in vitro but also
      markedly delayed progression of rat galactosemic cataract in vivo. Thus,
      diosgenin rich food can be recommended to diabetic subjects as dietary management
      to postpone the occurrence of sugar cataract, and diosgenin deserves further
      investigation for chronic diabetic complications.

PMID- 29038790
TI  - db/db Mice Exhibit Features of Human Type 2 Diabetes That Are Not Present in
      Weight-Matched C57BL/6J Mice Fed a Western Diet.
AB  - To understand features of human obesity and type 2 diabetes mellitus (T2D) that
      can be recapitulated in the mouse, we compared C57BL/6J mice fed a Western-style
      diet (WD) to weight-matched genetically obese leptin receptor-deficient mice
      (db/db). All mice were monitored for changes in body composition, glycemia, and
      total body mass. To objectively compare diet-induced and genetic models of
      obesity, tissue analyses were conducted using mice with similar body mass. We
      found that adipose tissue inflammation was present in both models of obesity. In
      addition, distinct alterations in metabolic flexibility were evident between WD
      fed mice and db/db mice. Circulating insulin levels are elevated in each model of
      obesity, while glucagon was increased only in the db/db mice. Although both WD
      fed and db/db mice exhibited adaptive increases in islet size, the db/db mice
      also displayed augmented islet expression of the dedifferentiation marker Aldh1a3
      and reduced nuclear presence of the transcription factor Nkx6.1. Based on the
      collective results put forth herein, we conclude that db/db mice capture key
      features of human T2D that do not occur in WD-fed C57BL/6J mice of comparable
      body mass.

PMID- 29038792
TI  - Neuroanatomical Relationships between Orexin/Hypocretin-Containing Neurons/Nerve
      Fibers and Nicotine-Induced c-Fos-Activated Cells of the Reward-Addiction
      Neurocircuitry.
AB  - Orexin/hypocretin-containing neurons in lateral hypothalamus (LH) are implicated
      in the neurobiology of nicotine addiction. However, the neuroanatomical
      relationships between orexin-neurons/nerve fibers and nicotine-activated cells
      within the reward-addiction neurocircuitry is not known. In the present study in
      mice, we first used c-Fos immunohistochemistry to identify CNS cells stimulated
      by an acute single injection of nicotine (NIC, 2 mg/kg, IP). Sequential double
      labelling was then performed to identify the location of orexin-containing
      neurons and nerve fibers with respect to NIC-induced c-Fos activated cells and/or
      tyrosine hydroxylase (TH) immunoreactive (IR) cells of the mesocorticolimbic
      reward-addiction pathways. Orexin-IR nerve fibers and terminals were detected at
      multiple sites of the NIC reward-addiction circuitry in close apposition to, and
      intermingled with, NIC-induced c-Fos-IR cells of locus coeruleus (LC), ventral
      tegmental area (VTA), nucleus accumbens (Acb), LH and paraventricular thalamic
      nucleus (PVT). Double-labelling of orexin with TH showed frequent contact between
      orexin-IR nerve fibers and noradrenergic cells of LC. However, there was
      infrequent contact between the orexinergic fibers and the TH-expressing
      dopaminergic cells of VTA, dorsal raphe nucleus (DR), posterior hypothalamus
      (DA11), arcuate hypothalamic nucleus (DA12) and periventricular areas (DA14). The
      close anatomical contact between orexinergic nerve fibers and NIC-activated cells
      at multiple sites of the reward-addiction pathways suggests that orexinergic
      projections from LH are likely to be involved in modulating activity of the
      neurons that are directly impacted by acute administration of nicotine.

PMID- 29038791
TI  - Traditional Chinese Medicine Protects against Cytokine Production as the
      Potential Immunosuppressive Agents in Atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disease caused by dyslipidemia and
      mediated by both innate and adaptive immune responses. Inflammation is a critical
      factor at all stages of atherosclerosis progression. Proinflammatory cytokines
      accelerate atherosclerosis progression, while anti-inflammatory cytokines
      ameliorate the disease. Accordingly, strategies to inhibit immune activation and
      impede immune responses towards anti-inflammatory activity are an alternative
      therapeutic strategy to conventional chemotherapy on cardiocerebrovascular
      outcomes. Since a number of Chinese medicinal plants have been used traditionally
      to prevent and treat atherosclerosis, it is reasonable to assume that the plants
      used for such disease may suppress the immune responses and the resultant
      inflammation. This review focuses on plants that have immunomodulatory effects on
      the production of inflammatory cytokine burst and are used in Chinese traditional
      medicine for the prevention and therapy of atherosclerosis.

PMID- 29038794
TI  - Biomaterials-based In Situ Tissue Engineering.

PMID- 29038793
TI  - Mechanisms of Cell Polarization.
AB  - Cell polarization is a key step in the migration, development, and organization
      of eukaryotic cells, both at the single cell and multicellular level. Research on
      the mechanisms that give rise to polarization of a given cell, and organization
      of polarity within a tissue has led to new understanding across cellular and
      developmental biology. In this review, we describe some of the history of
      theoretical and experimental aspects of the field, as well as some interesting
      questions and challenges for the future.

PMID- 29038797
TI  - Anthocyanin profile, antioxidant activity and enzyme inhibiting properties of
      blueberry and cranberry juices: a comparative study.
AB  - Cranberry (Vaccinium macrocarpon) and blueberry (Vaccinium myrtillus) juices are
      commonly consumed as a source of antioxidants. The aim of this study was to
      compare bioactivities as well as the differences in the polyphenol content and
      anthocyanin profile of both juices. Polyphenol and anthocyanin contents were
      quantified using spectrophotometric and chromatographic methods. Bioassays were
      carried out in terms of antioxidant properties in cell and cell free systems as
      well as inhibition of physiological enzymes that are targets involved in the
      prevention of chronic diseases (monoamine oxidase A, tyrosinase,
      acetylcholinesterase, alpha-glucosidase and dipeptidyl peptidase-4). Both juices
      contained a significant amount of anthocyanins (3.909 mg anthocyanins per mg
      extract for blueberry juice and 0.398 for cranberry juice) and also exhibited
      antioxidant properties against DPPH, superoxide radicals and hydrogen peroxide.
      These juices showed inhibitory effects on the enzymes, showing substantial
      potential as antioxidant, neuroprotective and anti-hyperglycaemic agents. The
      total anthocyanin and polyphenol content was higher in blueberry juice, which is
      indicative of a higher antioxidant activity. Both juices were also able to
      inhibit monoamine oxidase A, tyrosinase, alpha-glucosidase and dipeptidyl
      peptidase-4 in a dose-dependent manner. However, cranberry juice had a greater
      capacity than blueberry juice as an alpha-glucosidase inhibitor, revealing a
      similar activity to acarbose.

PMID- 29038796
TI  - Serious Adverse Events with Bevacizumab or Ranibizumab for Age-related Macular
      Degeneration: Meta-analysis of Individual Patient Data.
AB  - TOPIC: A comparison between ranibizumab and bevacizumab of the incidence of
      systemic serious adverse events (SAEs) among patients with neovascular age
      related macular degeneration (nAMD) who participated in a large-scale randomized
      trial. Use of individual patient data, rather than aggregate data, allowed
      adjustment for strong predictors of SAEs. CLINICAL RELEVANCE: Relative safety of
      ranibizumab and bevacizumab is important in choosing an anti-VEGF drug for the
      hundreds of thousands of patients with nAMD treated each year worldwide. METHODS:
      Results of a Cochrane aggregate meta-analysis of the relative efficacy and safety
      of bevacizumab and ranibizumab that used searches of bibliographic databases and
      clinical trial registries as of March 14, 2014 and hand searching were reviewed
      to identify 6 large-scale, multicenter clinical trials. Individual patient data
      on SAEs, assigned drug and dosing regimen, and baseline prognostic factors were
      requested from the leaders of the 6 trials. A two-stage approach was used to
      estimate relative risks and 95% confidence intervals (CIs) from Cox proportional
      hazards models adjusting for baseline prognostic factors. The primary outcome
      measure was development of >=1 SAE; secondary outcome measures were death,
      arteriothrombotic events, events associated with systemic anti-VEGF therapy, and
      events not associated with systemic anti-VEGF therapy. RESULTS: Individual
      patient data were received from 5 trials to provide information on 3052 patients.
      There were no large imbalances between drug groups on baseline factors. The
      adjusted relative risk (95% CI) for bevacizumab relative to ranibizumab was 1.06
      [(0.84, 1.35); p=0.61] for >=1 SAEs. For secondary outcomes, adjusted relative
      risks were 0.99 [ (0.69, 1.43); p=0.97] for death, 0.89 [ (0.62, 1.28); p=0.53]
      for arteriothrombotic events, 1.10 [ (0.81, 1.50); p=0.54] for events related to
      anti-VEGF treatment, and 1.11 [ (0.87, 1.40); p=0.40] for events not related to
      anti-VEGF treatment. CONCLUSION: Our findings support the absence of large
      differences in risk of systemic serious adverse events between these two anti
      VEGF drugs; i.e., relative risks of >=1.5 are unlikely. Because additional head
      to-head trials are unlikely, any further investigation of differential risk
      between anti-VEGF agents will only be achieved though post-marketing surveillance
      or through the interrogation of healthcare databases.

PMID- 29038798
TI  - Quantum and quasiclassical trajectory studies of rotational relaxation in Ar-N2+
      collisions.
AB  - The collision of N2+ with Ar is studied using quantum and classical methods. The
      dynamics was followed on a new potential energy surface based on ab initio
      energies computed at the UCCSD(T)-F12a/aug-cc-pVTZ level, using the correct
      analytical long range behaviour and a reproducing kernel representation.
      Comparison with multi-reference MRCI+Q calculations establish that UCCSD(T)-F12a
      is a sufficiently high level of theory for this problem. Results from quantum
      close coupling and quasiclassical trajectory calculations agree favourably with
      each other and the rates for inelastic collisions are lower than those from
      Langevin theory. This differs from previous calculations on a zero point
      corrected potential energy surface (PES) and indicates that such corrections,
      although potentially useful, should not be applied in the present case. Despite
      the rather large differences between the potential energy surfaces, the computed
      rates are within one order of magnitude of one another which suggests that the
      quality of the PES is not the main reason for the remaining disagreement between
      computation and experiment. Also, the fraction of inelastic rotational collisions
      exceeds 20% in all cases irrespective of whether quantum or classical dynamics is
      used. Previous experimental rate coefficients for N2+(nu = 0, j = 6) colliding
      with Ar suggest that the rotational quantum number is largely conserved. This can
      not be confirmed from any of the simulations and calls for new single molecule
      experiments.

PMID- 29038802
TI  - Viscous forces and bulk viscoelasticity near jamming.
AB  - When weakly jammed packings of soft, viscous, non-Brownian spheres are probed
      mechanically, they respond with a complex admixture of elastic and viscous
      effects. While many of these effects are understood for specific, approximate
      models of the particles' interactions, there are a number of proposed force laws
      in the literature, especially for viscous interactions. We numerically measure
      the complex shear modulus G* of jammed packings for various viscous force laws
      that damp relative velocities between pairs of contacting particles or between a
      particle and the continuous fluid phase. We find a surprising sensitive
      dependence of G* on the viscous force law: the system may or may not display
      dynamic critical scaling, and the exponents describing how G* scales with
      frequency can change. We show that this sensitivity is closely linked to manner
      in which viscous damping couples to floppy-like, non-affine motion, which is
      prominent near jamming.

PMID- 29038795
TI  - Immune engineering: from systems immunology to engineering immunity.
AB  - The smallpox vaccine represents the earliest attempt in engineering immunity. The
      recent success of chimeric antigen receptor T cells (CAR-T cells) in cancer once
      again demonstrates the clinical potential of immune engineering. Inspired by this
      success, diverse approaches have been used to boost various aspects of immunity:
      engineering dendritic cells (DCs), natural killer (NK) cells, T cells,
      antibodies, cytokines, small peptides, and others. With recent development of
      various high-throughput technologies (of which engineers, especially biomedical
      engineers/bioengineers contributed significantly), such as immune repertoire
      sequencing, and analytical methods, a systems level of understanding immunity (or
      the lack of it) beyond model animals has provided critical insights into the
      human immune system. This review focuses on recent progressed made in systems
      biology and the engineering of adaptive immunity.

PMID- 29038804
TI  - Insights into the interfacial structure-function of poly(ethylene glycol)
      decorated peptide-stabilised nanoscale emulsions.
AB  - The interfacial properties of nanoscale materials have profound influence on
      biodistribution and stability as well as the effectiveness of sophisticated
      surface-encoded properties such as active targeting to cell surface receptors.
      Tailorable nanocarrier emulsions (TNEs) are a novel class of oil-in-water
      emulsions stabilised by molecularly-engineered biosurfactants that permit single
      pot stepwise surface modification with related polypeptides that may be
      chemically conjugated or genetically fused to biofunctional moieties. We have
      probed the structure and function of poly(ethylene glycol) (PEG) used to decorate
      TNEs in this way. The molecular weight of PEG decorating TNEs has considerable
      impact on the zeta-potential of the emulsion particles, related to differential
      interfacial thickness of the PEG layer as determined by X-ray reflectometry. By
      co-modifying TNEs with an antibody fragment, we show that the molecular weight
      and density of PEG governs the competing parameters of accessibility of the
      targeting moiety and of shielding the interface from non-specific interactions
      with the environment. The fundamental understanding of the molecular details of
      the PEG layer that we present provides valuable insights into the structure
      function relationship for soft nanomaterial interfaces. This work therefore paves
      the way for further rational design of TNEs and other nanocarriers that must
      interact with their environment in controlled and predictable ways.

PMID- 29038805
TI  - "Switching on" the single-molecule magnet properties within a series of dinuclear
      cobalt(iii)-dysprosium(iii) 2-pyridyloximate complexes.
AB  - The use of 2-pyridinealdoxime (paoH), methyl 2-pyridyl ketone oxime (mepaoH),
      phenyl 2-pyridyl ketone oxime (phpaoH) and pyridine-2-amidoxime (NH2paoH) for the
      synthesis of dinuclear CoIII/DyIII complexes is described in the absence or
      presence of an external base. Complexes [CoDy(pao)3(NO3)3] (1),
      [CoDy(mepao)3(NO3)3] (2), [CoDy(phpao)3(NO3)3] (3) and
      [CoDy(NH2pao)3(NO3)3].3MeOH (4.3MeOH) have been isolated and their structures
      have been determined by single-crystal X-ray crystallography. The complexes
      crystallize in non-centrosymmetric (2, 3) or centrosymmetric (1, 4.3MeOH)
      trigonal space groups and form a family of triply-oximate bridged dinuclear
      Co(iii)-Dy(iii) complexes. The crystals of 1, 3 and 4.3MeOH contain mixtures of
      Delta and Lambda enantiomers, whereas complex 2 is enantiomerically pure
      (Lambda). A 3-fold crystallographic axis (C3) passes through two metal ions in
      all complexes. The low-spin CoIII and DyIII ions are bridged by three oximate
      groups belonging to the eta1:eta1:eta1:MU 2-pyridyloximate ligands. The CoIII
      centre is octahedrally coordinated by the six nitrogen atoms of the deprotonated
      organic ligands in a facial arrangement. The DyIII centre is bound to an O9 set
      of donor atoms, its coordination sphere being completed by three bidentate
      chelating nitrato groups. The coordination polyhedron around DyIII in 1 is best
      described as the Johnson tricapped trigonal prism, while the coordination
      geometries of the DyIII centres in 2, 3 and 4.3MeOH are best described as
      consisting of spherical tricapped trigonal prismatic coordination polyhedra. The
      spectroscopic data of the complexes are also reported and discussed in the infra
      red region in terms of the coordination modes of the ligands involved. The
      magnetic properties of these complexes were studied between 300 and 1.8 K
      revealing mainly the depopulation of the DyIIImj sublevels of the ground 6H15/2
      state. The intrinsic magnetic anisotropy of the DyIII centers is clearly observed
      by the non-superimposed magnetization (M) versus H/T data, but single-molecule
      magnet (SMM) properties were detected only for the mepao--containing complex 2.
      The origin of these properties in 2 is critically discussed and supported by
      computational studies.

PMID- 29038806
TI  - Kinetics of volatile impurity removal from silicon by electron beam melting for
      photovoltaic applications.
AB  - A full domain control model is established for impurity transportation in the
      liquid phase, gas-liquid interface and gas phase of silicon to analyze the
      dynamic mechanics of impurity removal. The results show that the overall mass
      transfer coefficient mainly depends on the temperature and the chamber pressure.
      Its value increases with the increase of temperature or the decrease of chamber
      pressure. Under the same melting condition, the order of the overall mass
      transfer coefficients for P, Al and Ca is kP > kAl > kCa, indicating that P is
      easier to remove by evaporation. Mass transfer in the gas phase is the rate
      controlling step for volatile impurity removal at the temperature above the
      melting point of silicon. The rate-controlling step transits to evaporation on
      the gas-liquid interface then to mass transfer in the liquid boundary layer as
      the temperature increases. During electron beam melting, the removal of P is
      controlled by both evaporation on the gas-liquid interface and mass transfer in
      the liquid boundary layer, and the removal of Al and Ca is controlled by
      evaporation on the gas-liquid interface.

PMID- 29038807
TI  - High thermoelectric performances of monolayer SnSe allotropes.
AB  - alpha-SnSe is one of the most promising thermoelectric materials with low thermal
      conductivity and a high power factor. Since the thermoelectric properties of a
      material have a strong dependence on its crystal structure, we study the
      energetic and thermoelectric properties of four new monolayer phases of SnSe
      (beta, gamma, delta and epsilon) together with alpha-SnSe using the ab initio
      density functional theory method. The calculated electronic structures show that
      all five phases are semiconductors with different band gaps. The alpha, beta,
      gamma, and delta phases have an indirect band gap with the hybridization of sp2
      orbitals, whereas the epsilon phase has a direct band with the hybridization of
      sp3 orbitals. The thermoelectric transport properties and coefficients are
      obtained from the electronic structure using semi-classical Boltzmann theory, and
      the results indicate that the four new phases of SnSe (beta, gamma, delta and
      epsilon) all have better thermoelectric properties compared with the reported
      alpha phase. The predicted ZT value for the beta-SnSe phase is 2.06 at 300 K,
      suggesting that it has great potential for novel thermoelectric applications.

PMID- 29038808
TI  - Decoration of trastuzumab with short oligonucleotides: synthesis and detailed
      characterization.
AB  - Trastuzumab (Herceptin(r)) is an FDA-approved therapeutic antibody currently
      employed in the treatment of metastatic stages of breast cancer. Herein, we
      propose a simple, fast and cost-effective methodology to conjugate trastuzumab
      with 22-mer 5' thiol-modified oligonucleotides using a bifunctional crosslinker.
      The conjugates were successfully characterized by MALDI-ToF MS and SDS-PAGE,
      obviating the need for enzymatic digestion and difficult chromatographic
      separations. Furthermore, ELISA was performed to ensure that trastuzumab activity
      is not affected by oligonucleotide conjugation.

PMID- 29038809
TI  - Selenoureas for anion binding as molecular logic gates.
AB  - The first example of a molecular logic gate based on selenourea/anion host-guest
      interaction that performs a ternary logic operation using an 1H-NMR easy to read
      response output is described here. Selenoureas are very versatile receptors for
      anion binding, capable of forming both mono- and bi-coordinated adducts at room
      temperature in solution.

PMID- 29038810
TI  - Planarization of B20 clusters by Si and C atom substitution.
AB  - An optimization strategy combining a global semi-empirical quantum mechanical
      search and all-electron density functional theory was adopted to determine the
      lowest energy structures of B19Si and B19C clusters. The planarization of a B20
      cluster by Si and C atom substitution was observed. The structural transition was
      from the double-ring tubular B20 to an almost perfect planar B19Si and a quasi
      planar bowl B19C. B19Si possessed a geometry with a central B atom surrounded by
      a six-membered ring and a 13-atom outer ring. B19C adopted a geometry with a B5C
      six-membered hole. Both Si and C atoms occupied peripheral positions. The
      observed planarization may be attributed to sp2 hybridization, changes in the
      peripheral bonding, and structural mechanics. Some properties, including the HOMO
      LUMO gaps, on-site charge on Si and C atoms, and deformed charge distribution,
      were discussed.

PMID- 29038811
TI  - Model-averaging of ab initio spectra for the absolute configuration assignment
      via vibrational circular dichroism.
AB  - Vibrational absorption and vibrational circular dichroism spectra (VA and VCD)
      have been recorded for two hybrid isoindolinone-phtalide stereoisomers dissolved
      in CDCl3. Density-functional calculations have been performed to determine their
      absolute configuration. A comparison of calculated and measured values has been
      made using several goodness-of-fit indicators, and also introducing a model
      averaging technique, taking into account the variation of calculated spectra with
      the details of the computational method. The model-averaging technique,
      preliminarily tested on two VCD spectra already assigned to two diastereomers of
      tadalafil, gives higher credibility to the ab initio calculations, and should be
      useful for other molecules with high flexibility and/or more than one stereogenic
      center.

PMID- 29038812
TI  - Sonogashira (Cu and amine free) and Suzuki coupling in air catalyzed via
      nanoparticles formed in situ from Pd(ii) complexes of chalcogenated Schiff bases
      of 1-naphthaldehyde and their reduced forms.
AB  - The reaction of 1-naphthaldehyde with 2-(phenylthio/seleno)ethylamine afforded
      air- and moisture-insensitive Schiff bases: C10H7-1-CH[double bond, length as m
      dash]N-CH2CH2EPh (L1: E = S; L2: E = Se). Then, on treatment with NaOAc and
      Li2PdCl4, palladacycles, [Pd(L1-H/L2-H)Cl] (1/2) were formed at room temperature,
      in which L1/L2 are ligated as an unsymmetric (C-, N, E) pincer. The reduction of
      >C[double bond, length as m-dash]N bonds of L1 and L2 with sodium borohydride
      gave C10H7-1-CH2NH-CH2CH2EPh (L3: E = S; L4: E = Se). The reactions of L3/L4 at
      room temperature, similar to those of L1/L2, resulted in the formation of complex
      [Pd(L3/L4)Cl2] (3/4), in which the ligand is coordinated in a bidentate (N, E)
      mode. The yield of all the complexes was >85%. Characterization by HR-MS, 1H,
      13C{1H} and 77Se{1H} NMR spectra of L1-L4 and their complexes 1-4 were performed.
      The structures of L1 and 1-4 were established with single-crystal X-ray
      diffraction. In all the complexes, the geometry of palladium was distorted square
      planar. The Pd-S bond distances in 1 and 3 were 2.426(12) and 2.259(2) A,
      respectively, whereas Pd-Se bond lengths (A) were 2.523(11) (2) and 2.369(10) (4)
      A. The catalytic activities of 1-4 were explored for copper- and amine-free
      Sonogashira and Suzuki-Miyaura coupling (SMC) of aryl halides under aerobic
      conditions. The amount of catalyst required for achieving good conversion was
      0.01 and 0.05 mol% for SMC and Sonogashira coupling, respectively. The conversion
      of some substrates reached a maximum in 1 and 2 h for Sonogashira coupling and
      SMC, respectively. The palladacycles as catalysts gave good conversion
      efficiency. The generation of palladium-containing nanoparticles (NPs) during
      both coupling reactions was observed. These were isolated and HR-TEM studies were
      performed on them and revealed their size as ~2-7 nm. The SEM-EDX analysis
      indicated the presence of organochalcogen ligands or their fragments in the
      samples. They independently catalyzed both reactions. Therefore, the role of 1-4
      in catalysis undoubtedly exists. For Sonogashira coupling, the formation and role
      of such Pd-based NPs under aerobic conditions were observed for the first time.
      The complexes 1-4 showed the potential for reuse, as in the eighth cycle,
      conversion dropped by only 20%.

PMID- 29038813
TI  - Targeted tumor SPECT/CT dual mode imaging using multifunctional RGD-modified low
      generation dendrimer-entrapped gold nanoparticles.
AB  - Multifunctional low-generation dendrimer-entrapped gold nanoparticles (Au DENPs)
      were designed and synthesized. The formed Au DENPs modified with an arginine
      glycine-aspartic peptide and labeled with 99mTc possess a uniform size
      distribution, desirable colloidal stability and biocompatibility, and can be used
      as a promising nanoprobe for targeted SPECT/CT imaging of alphavbeta3 integrin
      expressing tumors.

PMID- 29038814
TI  - Selective cytotoxicity and luminescence imaging of cancer cells with a
      dipicolinato-based EuIII complex.
AB  - Four new species [Ln(dipicNH2)3]3- (Ln = LaIII, EuIII, GdIII, TbIII), with the
      ligand dipicNH22- (dipic = dipicolinato), were synthesized. Incubation of the
      EuIII complex with glioma NG97 and pancreatic cancer PANC1 cells showed that it
      penetrates the cell membrane and can be used to image the cells, while also being
      moderately cytotoxic.

PMID- 29038816
TI  - Ruthenium-catalysed sigma-activation for remote meta-selective C-H
      functionalisation.
AB  - The search for selective C-H functionalisation has enabled some of the most
      elegant techniques in modern catalysis. Herein, we review the rapidly expanding
      field of ruthenium catalysed sigma-activation as a tool in the selective meta-C-H
      functionalisation of arenes.

PMID- 29038817
TI  - Silver-induced self-immolative Cl-F exchange fluorination of arylsulfur
      chlorotetrafluorides: synthesis of arylsulfur pentafluorides.
AB  - A novel strategy for the synthesis of arylsulfur pentafluorides by silver
      carbonate-induced Cl-F exchange fluorination of arylsulfur chlorotetrafluorides
      is reported. This fluorination does not require any exogenous fluoride sources.
      Rather, the reaction proceeds via the self-immolation of the substrate Ar-SF4Cl.

PMID- 29038815
TI  - Distinct oligomerization and fibrillization dynamics of amyloid core sequences of
      amyloid-beta and islet amyloid polypeptide.
AB  - A direct observation of amyloid aggregation from isolated peptides to cross-beta
      fibrils is crucial for understanding the nucleation-dependence process, but the
      corresponding macroscopic timescales impose a major computational challenge.
      Using rapid all-atom discrete molecular dynamics simulations, we capture the
      oligomerization and fibrillization dynamics of the amyloid core sequences of
      amyloid-beta (Abeta) in Alzheimer's disease and islet amyloid polypeptide (IAPP)
      in type-2 diabetes, namely Abeta16-22 and IAPP22-28. Both peptides and their
      mixture spontaneously assemble into cross-beta aggregates in silico, but follow
      distinct pathways. Abeta16-22 is highly aggregation-prone with a funneled free
      energy basin toward multi-layer beta-sheet aggregates. IAPP22-28, on the other
      hand, features the accumulation of unstructured oligomers before the nucleation
      of beta-sheets and growth into double-layer beta-sheet aggregates. In the
      presence of Abeta16-22, the aggregation of IAPP22-28 is promoted by forming co
      aggregated multi-layer beta-sheets. Our study offers a detailed molecular insight
      to the long-postulated oligomerization-nucleation process in the amyloid
      aggregations.

PMID- 29038818
TI  - A C-HCR assembly of branched DNA nanostructures for amplified uracil-DNA
      glycosylase assays.
AB  - An autonomous nonenzymatic DNA machine has been successfully engineered based on
      a two-layered cascaded hybridization chain reaction (C-HCR) circuit, in which the
      tandem outputs of the upstream HCR-1 unit activate the downstream HCR-2 unit to
      induce successive repeated hybridizations, generating branched DNA structures and
      enabling sensitive and selective detection of uracil-DNA glycosylase and its
      inhibitors.

PMID- 29038819
TI  - Over two-orders of magnitude enhancement of the photocatalytic hydrogen evolution
      activity of carbon nitride via mediator-free decoration with gold-organic
      microspheres.
AB  - A mediator and Pt free photocatalytic system is created for H2 production over
      AuNPs/g-C3N4 hybrids under visible light irradiation. In contrast to pure g-C3N4
      and state-of-the-art 3 wt% Pt loaded g-C3N4, ingeniously decorating minute AuNPs
      onto g-C3N4 can enhance the catalytic activity by about 348 and 25 times,
      respectively.

PMID- 29038820
TI  - [Primary spontaneous pneumothorax : Is there an impact of weather conditions?]

PMID- 29038821
TI  - [Lower right abdominal pain and anal bleeding : A rare cause for nonspecific
      complaints].

PMID- 29038822
TI  - [An unusual cause of jejunal obstruction].

PMID- 29038823
TI  - Left ventricular twist in hypertrophic cardiomyopathy : Predictor of nonsustained
      ventricular tachycardia.
AB  - BACKGROUND: We investigated the efficacy of clinical and classic
      echocardiographic parameters in predicting the occurrence of nonsustained
      ventricular tachycardia (NsVT) in patients with hypertrophic cardiomyopathy
      (HCM). METHODS: The study comprised 59 patients with HCM (47 male, [80%]; mean
      age, 48.48 +/- 14.16 years). Clinical, electrocardiographic, as well as classic
      two-dimensional and speckle-tracking echocardiography (STE) data were collected.
      All patients had Holter monitoring within 24-72 h of the echocardiographic
      examination. NsVT was defined as three or more consecutive premature wide QRS
      complexes with a heart rate of > 100 bpm. The patient population was categorized
      into groups based on the occurrence or absence of NsVT on the 24-h Holter
      recordings. RESULTS: NsVT was observed in 17 patients (29%). In these patients,
      higher twist (14.4 +/- 3.8 vs.18 +/- 7.9; p = 0.02), higher apical rotation (8.7
      +/- 4.2 vs. 12.2 +/- 7; p = 0.02), higher sudden cardiac death risk score (4.4 +/
      2.2 vs. 7 +/- 3.3; p = 0.007), and decreased global longitudinal peak strain
      (GLPS; -12.8 +/- 3.1 vs. -10.6 +/- 2.8; p = 0.014) were observed. In the
      multivariate logistic regression analysis, including GLPS and twist, GLPS (Odds
      Ratio [OR]: 1.406; 95% CI: 1.087-1.818; p = 0.009) and twist (OR: 1.236; 95% CI:
      1.056-1.446; p = 0.008) were found to be independent predictors of NsVT. In the
      receiver operating characteristic curve analysis, GLPS < -11.9% predicted NsVT
      with 82% sensitivity and 60% specificity (area under the curve [AUC]: 0.70; p =
      0.014) and twist > 15.2 degrees  predicted NsVT with 70% sensitivity and 58%
      specificity (AUC: 0.69; p = 0.027). CONCLUSION: Decreased GLPS and increased
      twist were predictive of NsVT in HCM patients. Parameters that can easily be
      measured with STE can help detect patients who may develop arrhythmia.

PMID- 29038824
TI  - Memantine add-on to clozapine treatment for residual negative symptoms of
      schizophrenia.

PMID- 29038825
TI  - Detection system for Saccharomyces cerevisiae with phenyl acrylic acid
      decarboxylase gene (PAD1) and sulphur efflux gene (SSU1) by multiplex PCR.
AB  - Production of wine with selected yeast strains is a common enological practice
      followed for the production of wine with desirable organoleptic properties and to
      guarantee the homogeneity of successive vintages. Sulphur dioxide tolerance and
      phenyl acrylic acid resistance are the enological traits essential for the
      survivability of the yeast during fermentation. The present study describes the
      detection of S. cerevisiae with enological traits, such as phenyl acrylic acid
      resistance and sulphur dioxide tolerance in a single test. Phenyl acrylic acid
      decarboxylase (PAD1) and sulphite efflux genes (SSU1) were detected by multiplex
      PCR, thus confirming the specificity of primers. A single cocktail of all
      reagents required for the simultaneous detection of both these genes was
      designed. The ready-to-use formulation optimized was stable at 4 and - 20 
      degrees C for 6 months. The amplification of phenyl acrylic acid decarboxylase
      and sulphite efflux genes, validated the suitability of the ready-to-use
      formulation for the detection of S. cerevisiae in food samples. The ready-to-use
      formulation optimized, minimizes the end user requirements for the detection of
      S. cerevisiae. Thus, the method was suitable for the identification of S.
      cerevisiae strains from a mixture of yeast prior to the sequencing analysis,
      thereby reducing the cost and time of screening.

PMID- 29038826
TI  - Compartment Pressure Monitoring After Thyroid Surgery: A Possible Method to
      Detect a Rebleeding: Reply.

PMID- 29038828
TI  - Using the WHO Surgical Safety Checklist to Direct Perioperative Quality
      Improvement at a Surgical Hospital in Cambodia: The Importance of Objective
      Confirmation of Process Completion.
AB  - BACKGROUND: The WHO surgical safety checklist (SSC) is known to prevent
      postoperative complications; however, strategies for effective implementation are
      unclear. In addition to cultural and organizational barriers faced by high-income
      countries, resource-constrained settings face scarcity of durable and consumable
      goods. We used the SSC to better understand barriers to improvement at a trauma
      hospital in Battambang, Cambodia. METHODS: We introduced the SSC and trained data
      collectors to observe surgical staff performing the checklist. Members of the
      research team observed cases and data collection. After 3 months, we modified the
      data collection tool to focus on infection prevention and elicit more accurate
      responses. RESULTS: Over 16 months we recorded data on 695 operations (304 cases
      using the first tool and 391 cases with the modified tool). The first tool
      identified five items as being in high compliance, which were then excluded from
      further assessment. Two items-instrument sterility confirmation and sponge
      counting-were identified as being misinterpreted by the data collectors' tool.
      These items were reworded to capture objective assessment of task completion.
      Confirmation of instrument sterility was initially never performed but rectified
      to >95% compliance; sponge counting and prophylactic antibiotic administration
      were consistently underperformed. CONCLUSIONS: Staff complied with communication
      elements of the SSC and quickly adopted process improvements. The wording of our
      data collection tool affected interpretation of compliance with standards.
      Material resources are not the primary barrier to checklist implementation in
      this setting, and future work should focus on clarification of protocols and
      objective confirmation of tasks.

PMID- 29038829
TI  - The Brain Drain Myth: Retention of Specialist Surgical Graduates in East, Central
      and Southern Africa, 1974-2013.
AB  - BACKGROUND: This study assesses the retention of specialist surgical graduates
      from training programmes across eight countries in East, Central and Southern
      Africa from 1974 to 2013. It addresses the gap in existing data by analysing
      retention rates of surgical graduates by comparing graduating institution to
      current location. Data were assessed by country, region, specialty and gender
      with a view to informing national and regional healthcare and education
      strategies. METHODS: Twenty-five institutions train surgeons in the ten countries
      covered by the College of Surgeons of East, Central and Southern Africa (COSECSA)
      24 Universities and the College itself. These institutions were requested in
      November 2014 to supply details of graduates from their postgraduate surgical
      training programmes. Complete graduate lists were returned by the College and 14
      universities by March 2016. These surgical graduates were compared against the
      database of current practising surgeons in the region held by COSECSA. Data were
      cross-checked against medical council registers, surgical society records, and
      with members and fellows of COSECSA. RESULTS: Data were incomplete for 126
      surgical graduates. Of the remaining 1038 surgical graduates, 85.1% were retained
      in the country they trained in, while 88.3% were retained within the COSECSA
      region. Ninety-three per cent (93.4%) were retained within Africa. Of the eight
      countries, Malawi had the highest retention rate with 100% of surgical graduates
      remaining in country, while Zimbabwe had the lowest rate with 65.5% remaining.
      CONCLUSION: High surgical graduate retention rates across the region indicate
      that the expansion of national surgical training initiatives is an effective
      solution to addressing the surgical workforce shortage in East, Central and
      Southern Africa and counters long-held arguments regarding brain drain in this
      region.

PMID- 29038827
TI  - Is Routine Intraoperative Contrast-Enhanced Ultrasonography Useful During Whole
      Liver Transplantation?
AB  - BACKGROUND: Vascular complications following liver transplantation (LT) may
      result from technical deficiencies. Intraoperative diagnosis remains challenging
      but can prevent serious delayed complications. Intraoperative Doppler
      ultrasonography (IOUS) represents the gold standard for imaging, although it
      requires radiological skills. Contrast-enhanced ultrasonography has been reported
      during postoperative assessments, but never intraoperatively (CE-IOUS). The aim
      of this study was to assess the feasibility of routine CE-IOUS, to evaluate its
      impact on surgical strategy and its usefulness. METHODS: All 553 whole LTs
      performed in our tertiary centre between 01/2010 and 12/2014 were reviewed. We
      compared perioperative outcomes and long-term survival in IOUS (n = 370) versus
      CE-IOUS (n = 103) groups. Secondarily, the seven cases where the two imaging
      findings conflicted (CE+ Group) were matched 1:2 and compared with an exclusively
      IOUS procedure (CE- Group, n = 14) to assess the consequences of a specific CE
      guided strategy. RESULTS: CE-IOUS assessments were successful in 100% of cases,
      without any adverse effects. Vascular complications and patient/graft survival
      rates were identical in the IOUS and CE-IOUS groups (p = 0.65, 0.95 and 0.86,
      respectively). CE-IOUS confirmed IOUS findings in 93% of cases (n = 96) and led
      to the realization of an additional procedure (median arcuate ligament lysis) and
      six conservative strategies despite poor arterial (n = 5) or venous flow (n = 1)
      under Doppler analysis. The CE+ and CE- groups presented statistically identical
      perioperative and long-term outcomes. CONCLUSION: This study demonstrated the
      feasibility of CE-IOUS during whole LT. However, we failed to demonstrate any
      advantages of CE-IOUS over IOUS. Therefore, IOUS currently remains the gold
      standard imaging technique for the intraoperative assessment of vascular patency.

PMID- 29038830
TI  - A Distance Blended Learning Program to Upgrade the Clinical Competence of
      District Non-doctor Anesthesia Providers in Nepal.
AB  - BACKGROUND: Across Nepal, anesthesia at a district level is provided mostly by
      non-doctor anesthesia providers (anesthesia assistants-AAs). Nepal's Government
      recognized the need to sustain competence with continuous professional
      development and to upgrade 6-month trained working AAs to professional
      equivalence with the new national standard of 12-month training. As they are
      essential district health workers and AA clinical training sites are full, an
      innovative distance blended learning, competency-based, upgrade 1-year course was
      developed and conducted in 2014-2017 for two batches. METHODS: The course content
      was developed over 18 months by a team of Nepali and overseas AA training
      experts. The 1-year course started with a refresher course, continued with tablet
      based 12-month self-learning modules and clinical case logs, regular educational
      mentor communication, midcourse 2-week contact time in an AA training site,
      regular text messaging and ended with clinical examination and multiple-choice
      questions. Tablet content included 168 new case studies, pre- and posttests,
      video lectures, matching exercises and a resource library. All module work and
      logged clinical cases were uploaded centrally, where clinical mentors were able
      to review work. Clinical skills were upgraded, as needed, through direct clinical
      contact midway through the course. Quantitative and qualitative course
      assessments were included. RESULTS: Fourteen working AAs in first batch and eight
      working AAs in second batch from district, zonal and mission hospitals across
      Nepal were enrolled. All remained working at their hospitals throughout the
      course, and there were no significant tablet problems inhibiting course
      completion. Twenty-one AAs completed all modules successfully with time required
      for module completion averaging 19.2 h (range 11.2-32). One AA left the course
      after 3 months with a personal problem. Subjectively, AAs felt that the obstetric
      and pediatric modules were more difficult; lowest marks were objectively seen in
      the airway module. Clinical mentors averaged 8.2 h mentoring review work per
      module with direct student communication of 2.9 h per module per month.
      Participants logged a total of 5473 clinical cases, ranging between 50 and 788
      cases each. Complications were recorded; outcomes were good. Challenges were the
      national IT infrastructure making data synchronization difficult and the lack of
      clinical exposure at some AA's hospitals. Nineteen AAs attended the final
      examination, and all passed. Two AAs withdrew before the final examination period
      due to personal and logistic reasons. CONCLUSION: This is the first use of
      distance blended learning to upgrade district health workers in Nepal and perhaps
      for non-doctor anesthesia providers globally. Key success factors were motivated
      students, cultural and contextualized clinical content, good educational
      mentoring relationships with regular communication, central IT and motivational
      support, and face-to-face midcourse clinical contact time.

PMID- 29038831
TI  - Recovery from sublethal damage and potentially lethal damage : Proton beam
      irradiation vs. X-ray irradiation.
AB  - PURPOSE: In order to clarify the biological response of tumor cells to proton
      beam irradiation, sublethal damage recovery (SLDR) and potentially lethal damage
      recovery (PLDR) induced after proton beam irradiation at the center of a 10 cm
      spread-out Bragg peak (SOBP) were compared with those seen after X-ray
      irradiation. METHODS: Cell survival was determined by a colony assay using EMT6
      and human salivary gland tumor (HSG) cells. First, two doses of 4 Gy/GyE (Gray
      equivalents, GyE) were given at an interfraction interval of 0-6 h. Second, five
      fractions of 1.6 Gy/GyE were administered at interfraction intervals of 0-5 min.
      Third, a delayed-plating assay involving cells in plateau-phase cultures was
      conducted. The cells were plated in plastic dishes immediately or 2-24 h after
      being irradiated with 8 Gy/GyE of X-rays or proton beams. Furthermore, we
      investigated the degree of protection from the effects of X-rays or proton beams
      afforded by the radical scavenger dimethyl sulfoxide to estimate the contribution
      of the indirect effect of radiation. RESULTS: In both the first and second
      experiments, SLDR was more suppressed after proton beam irradiation than after X
      ray irradiation. In the third experiment, there was no difference in PLDR between
      the proton beam and X-ray irradiation conditions. The degree of protection tended
      to be higher after X-ray irradiation than after proton beam irradiation.
      CONCLUSION: Compared with that seen after X-ray irradiation, SLDR might take
      place to a lesser extent after proton beam irradiation at the center of a 10 cm
      SOBP, while the extent of PLDR does not differ significantly between these two
      conditions.

PMID- 29038832
TI  - Dynamics of rectal balloon implant shrinkage in prostate VMAT : Influence on
      anorectal dose and late rectal complication risk.
AB  - PURPOSE: To assess the effect of a shrinking rectal balloon implant (RBI) on the
      anorectal dose and complication risk during the course of moderately
      hypofractionated prostate radiotherapy. METHODS: In 15 patients with localized
      prostate cancer, an RBI was implanted. A weekly kilovolt cone-beam computed
      tomography (CBCT) scan was acquired to measure the dynamics of RBI volume and
      prostate-rectum separation. The absolute anorectal volume encompassed by the 2 Gy
      equieffective 75 Gy isodose (V75Gy) was recalculated as well as the mean
      anorectal dose. The increase in estimated risk of grade 2-3 late rectal bleeding
      (LRB) between the start and end of treatment was predicted using nomograms. The
      observed acute and late toxicities were evaluated. RESULTS: A significant
      shrinkage of RBI volumes was observed, with an average volume of 70.4% of
      baseline at the end of the treatment. Although the prostate-rectum separation
      significantly decreased over time, it remained at least 1 cm. No significant
      increase in V75Gy of the anorectum was observed, except in one patient whose RBI
      had completely deflated in the third week of treatment. No correlation between
      mean anorectal dose and balloon deflation was found. The increase in predicted
      LRB risk was not significant, except in the one patient whose RBI completely
      deflated. The observed toxicities confirmed these findings. CONCLUSIONS: Despite
      significant decrease in RBI volume the high-dose rectal volume and the predicted
      LRB risk were unaffected due to a persistent spacing between the prostate and the
      anterior rectal wall.

PMID- 29038833
TI  - Tips and tricks for uterosacral ligament suspension: how to avoid ureteral
      injury.
AB  - INTRODUCTION AND HYPOTHESIS: Uterosacral ligament (USL) suspension is an
      effective and versatile surgical technique for repairing pelvic organ prolapse.
      However, ureteral injury is a feared complication that may act as a significant
      deterrent to the use of USL suspension. The aim of the video is to provide key
      steps to minimize the risk of ureteral injury while achieving successful
      transvaginal USL suspension. METHODS: The featured video provides a series of
      surgical tips and tricks that can be applied to protect the ureters while
      achieving USL suspension whether the procedure contemplated is vaginal
      hysterectomy, vaginal vault repair after hysterectomy, or hysteropexy. RESULTS:
      The tips and tricks are classified into four categories: identification of the
      USLs, identification of the ureters, passage of the sutures, and final measures.
      CONCLUSIONS: The USL suspension technique requires adequate surgical training and
      an understanding of pelvic anatomy. This tips and tricks video tutorial may be an
      important tool for improving surgical know-how, and thus for reducing the risk of
      ureteral injury. In particular, identification of the USLs and ureters, proper
      suture positioning and final cystoscopy are key points to minimize ureteral
      damage.

PMID- 29038834
TI  - The treatment of post-hysterectomy vaginal vault prolapse: a systematic review
      and meta-analysis.
AB  - INTRODUCTION AND HYPOTHESIS: The treatment of post-hysterectomy vaginal vault
      prolapse (VVP) has been investigated in several randomized clinical trials
      (RCTs), but a systematic review of the topic is still lacking. The aim of this
      study is to compare the effectiveness of treatments for VVP. METHODS: We
      performed a systematic review and meta-analysis of the literature on the
      treatment of VVP found in PubMed and Embase. Reference lists of identified
      relevant articles were checked for additional articles. A network plot was
      constructed to illustrate the geometry of the network of the treatments included.
      Only RCTs reporting on the treatment of VVP were eligible, conditional on a
      minimum of 30 participants with VVP and a follow-up of at least 6 months.
      RESULTS: Nine RCTs reporting 846 women (ranging from 95 to 168 women) met the
      inclusion criteria. All surgical techniques were associated with good subjective
      results, and without differences between the compared technique, with the
      exception of the comparison of vaginal mesh (VM) vs laparoscopic sacrocolpopexy
      (LSC). LSC is associated with a higher satisfaction rate. The anatomical results
      of the sacrocolpopexy (laparoscopic, robotic [RSC]. and abdominal [ASC]) are the
      best (62-91%), followed by the VM. However, the ranges of the anatomical outcome
      of VM were wide (43-97%). The poorest results are described for the sacrospinal
      fixation (SSF; 35-81%), which also correlates with the higher reoperation rate
      for pelvic organ prolapse (POP; 5-9%). The highest percentage of complications
      were reported after ASC (2-19%), VM (6-29%), and RSC (54%). Mesh exposure was
      seen most often after VM (8-21%). The rate of reoperations carried out because of
      complications, recurrence prolapse, and incontinence of VM was 13-22%. Overall,
      sacrocolpopexy reported the best results at follow-up, with an outlier of one
      trial reporting the highest reoperation rate for POP (11%). The results of the
      RSC are too small to make any conclusion, but LSC seems to be preferable to ASC.
      CONCLUSIONS: A comparison of techniques was difficult because of heterogeneity;
      therefore, a network meta-analysis was not possible. All techniques have proved
      to be effective. The reported differences between the techniques were negligible.
      Therefore, a standard treatment for VVP could not be given according to this
      review.

PMID- 29038835
TI  - Interaction between LRP5 and periostin gene polymorphisms on serum periostin
      levels and cortical bone microstructure.
AB  - : We investigated the interaction between periostin SNPs and the SNPs of the
      genes assumed to modulate serum periostin levels and bone microstructure in a
      cohort of postmenopausal women. We identified an interaction between LRP5 SNP
      rs648438 and periostin SNP rs9547970 on serum periostin levels and on radial
      cortical porosity. PURPOSE: The purpose of this study is to investigate the
      interaction between periostin gene polymorphisms (SNPs) and other genes
      potentially responsible for modulating serum periostin levels and bone
      microstructure in a cohort of postmenopausal women. METHODS: In 648
      postmenopausal women from the Geneva Retirees Cohort, we analyzed 6 periostin
      SNPs and another 149 SNPs in 14 genes, namely BMP2, CTNNB1, ESR1, ESR2, LRP5,
      LRP6, PTH, SPTBN1, SOST, TGFb1, TNFRSF11A, TNFSF11, TNFRSF11B and WNT16.
      Volumetric BMD and bone microstructure were measured by high-resolution
      peripheral quantitative computed tomography at the distal radius and tibia.
      RESULTS: Serum periostin levels were associated with radial cortical porosity,
      including after adjustment for age, BMI, and years since menopause (p = 0.036).
      Sixteen SNPs in the ESR1, LRP5, TNFRSF11A, SOST, SPTBN1, TNFRSF11B and TNFSF11
      genes were associated with serum periostin levels (p range 0.03-0.001) whereas 26
      SNPs in 9 genes were associated with cortical porosity at the radius and/or at
      the tibia. WNT 16 was the gene with the highest number of SNPs associated with
      both trabecular and cortical microstructure. The periostin SNP rs9547970 was also
      associated with cortical porosity (p = 0.04). In particular, SNPs in LRP5, ESR1
      and near the TNFRSF11A gene were associated with both cortical porosity and serum
      periostin levels. Eventually, we identified an interaction between LRP5 SNP
      rs648438 and periostin SNP rs9547970 on serum periostin levels (interaction p =
      0.01) and on radial cortical porosity (interaction p = 0.005). CONCLUSION: These
      results suggest that periostin expression is genetically modulated, particularly
      by polymorphisms in the Wnt pathway, and is thereby implicated in the genetic
      variation of bone microstructure.

PMID- 29038836
TI  - Automated DXA-based finite element analysis for hip fracture risk stratification:
      a cross-sectional study.
AB  - : Fracture risk indices (FRIs) generated from DXA-based finite element analysis
      were associated with hip fracture independent of FRAX score computed with femoral
      neck bone mineral density (BMD). Prospective studies are warranted to determine
      whether FRIs represent an improvement over BMD for predicting incident hip
      fractures. INTRODUCTION: The study aims to examine the association between prior
      hip fracture and FRIs derived from automated finite element analysis (FEA) of DXA
      hip scans. Femoral neck, intertrochanteric, and subtrochanteric FRIs were
      calculated as the von Mises stress induced by a sideways fall divided by the bone
      yield stress over the specified region of interest (ROI). METHODS: Using the
      Manitoba Bone Mineral Density Database, we selected women age >= 65 years with
      femoral neck T-scores below - 1 and no osteoporosis treatment. From this
      population, we identified 324 older women with hip fracture before DXA testing
      and a random sample of 658 non-fracture controls. FRIs were derived from the
      anonymized DXA scans. Logistic regression models were used to estimate odds
      ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between
      FRIs (per SD increase) and hip fracture. RESULTS: After adjusting for FRAX score
      (hip fracture with BMD), femoral neck FRI (OR 1.36, 95% CI 1.13, 1.64),
      intertrochanteric FRI (OR 1.81, 95% CI 1.44, 2.27), and subtrochanteric FRI (OR
      2.09, 95% CI 1.68, 2.60) were associated with hip fracture. Intertrochanteric and
      subtrochanteric FRIs gave significantly higher c-statistics (all P <= 0.05) than
      femoral neck BMD. Subgroup analyses showed that all FRIs were more strongly
      associated with hip fracture in women who were younger and had higher body mass
      index (BMI) or non-osteoporotic BMD (all P interaction < 0.1). CONCLUSIONS: FRIs
      derived from DXA-based FEA were independently associated with prior hip fracture,
      suggesting that they could potentially improve hip fracture risk assessment.

PMID- 29038838
TI  - Respiratory sensitization: toxicological point of view on the available assays.
AB  - Respiratory sensitization as a consequence of exposure to chemical products has
      increased over the last decades, leading to an increase of morbidity. The
      increased use of synthetic compounds resulted in an exponential growth of
      substances to which we are potentially exposed on a daily basis. Some of them are
      known to induce respiratory sensitization, meaning that they can trigger the
      development of allergies. In the past, animal studies provided useful results for
      the understanding of mechanisms involved in the development of respiratory
      allergies. However, the mechanistic understanding of the involved cellular
      effects is still limited. Currently, no in vitro or in vivo models are validated
      to identify chemical respiratory sensitizers. Nonetheless, chemical respiratory
      sensitizers elicit a positive response in validated assays for skin
      sensitization. In this review, we will discuss how these assays could be used for
      respiratory sensitization and if necessary, what can be learnt from these assays
      to develop a model to assess the respiratory sensitizing potential of chemicals.
      In the last decades, much work has been done to study the respiratory toxicity of
      inhaled compounds especially in developing in vitro assays grown at the air
      liquid interface. We will discuss how possibly the tests currently used to
      investigate general particle toxicity could be transformed to investigate
      respiratory sensitization. In the present review, we describe the most known
      mechanism involved in the sensitization process and the experimental in vivo and
      alternative in vitro models, which are currently available and how to adapt and
      improve existing models to study respiratory sensitization.

PMID- 29038837
TI  - Reduced kidney function is associated with BMD, bone loss and markers of mineral
      homeostasis in older women: a 10-year longitudinal study.
AB  - : Kidney function decreases with age; however, the long-term influence on bone
      density (BMD) in older women already at risk of osteoporosis is unknown. We
      followed kidney function and bone loss for 10 years. Declining kidney function
      was adversely associated with bone loss and mineral homeostasis in old women,
      though it attenuated with advanced aging. INTRODUCTION: Existing studies do not
      fully address the relationship between kidney function and bone metabolism with
      advanced aging in Caucasian women. This study describes the association between
      kidney function, BMD, bone loss and bone metabolism in older women and provides a
      review of the available literature for context. METHODS: We studied participants
      from the OPRA cohort with follow-up after 5 and 10 years. Using plasma cystatin C
      (cysC), estimated glomerular function rate (eGFR) was evaluated at age 75 (n =
      981), 80 (n = 685) and 85 (n = 365). Women were stratified into "normal" function
      (CKD stages 1-2), "intermediate" (stage 3a) and "poor" (stages 3b-5), and outcome
      measures-BMD, bone loss and markers of mineral homeostasis-were compared.
      RESULTS: Femoral neck (FN) BMD positively associated with kidney function at 75
      years old ([Formula: see text] = 0.001, p = 0.028) and 80 years old ([Formula:
      see text] = 0.001, p = 0.001), although with small effect size. Prevalence of
      osteoporosis (FN T-score <= - 2.5) did not differ with kidney function. Measured
      at age 75, women with poor kidney function had higher annual percentage bone loss
      over 5 years compared to those with normal function (2.3%, 95% CI 1.8-2.8 versus
      1.3%, 95% CI 1.1-1.5, p = 0.007), although not when measured from age 80 or 85.
      Additionally, markers of mineral homeostasis (PTH, phosphate, vitamin D,
      calcium), CRP and osteocalcin differed by kidney function. CONCLUSIONS: In old
      women, kidney function is associated with BMD, bone loss and altered mineral
      homeostasis; probably, a relationship attenuated in the very elderly.

PMID- 29038839
TI  - Hepatotoxic combination effects of three azole fungicides in a broad dose range.
AB  - Single active substances of pesticides are thoroughly examined for their toxicity
      before approval. In this context, the liver is frequently found to be the main
      target organ. Since consumers are generally exposed to multiple residues of
      different active substances via the diet, it is important to analyse combinations
      of active substances for potential mixture effects. For the (tri-)azoles, a group
      of agricultural fungicides and antifungal drugs, combination effects on the liver
      are likely because of a similar mode of action. Hepatotoxic effects of mixtures
      of two triazoles (cyproconazole and epoxiconazole) and an imidazole (prochloraz)
      were investigated in a 28-day feeding study in rats at three dose levels ranging
      from a typical toxicological reference value to a clear effect dose. Test
      parameters included organ weights, clinical chemistry, histopathology and
      morphometry. In addition, molecular parameters were investigated by means of
      pathway-focused gene expression arrays, quantitative real-time PCR and enzyme
      activity assays. Effects were compared to those caused by the individual
      substances as observed at the same dose levels in a previous study. Mixture
      effects were substantiated by increases in relative and absolute liver weights,
      histopathological findings and alterations in clinical chemistry parameters at
      the top dose level. On the molecular level also at lower dose levels, additive
      effects could be observed for the induction of several cytochrome P 450 enzymes
      (Cyp1a1, Cyp2b1, Cyp3a2), transporters (Abcb1a, Abcc3) and of genes encoding for
      enzymes involved in fatty acid or phospholipid metabolism (Ppargc1a, Sc4 mol). In
      most cases, treatment with mixtures caused a more pronounced effect as compared
      to the individual substances. However, the assumption of dose additivity was in
      general sufficiently conservative to cover mixture effects observed under the
      conditions of the present study.

PMID- 29038840
TI  - GABAA receptor subtype selectivity of the proconvulsant rodenticide TETS.
AB  - The rodenticide tetramethylenedisulfotetramine (TETS) is a potent convulsant
      (lethal dose in humans 7-10 mg) that is listed as a possible threat agent by the
      United States Department of Homeland Security. TETS has previously been studied
      in vivo for toxicity and in vitro in binding assays, with the latter
      demonstrating it to be a non-competitive antagonist on GABAA receptors. To
      determine whether TETS exhibits subtype selectivity for a particular GABAA
      receptor combination, we used whole-cell patch-clamp to determine the potency of
      TETS on the major synaptic and extrasynaptic GABAA receptors associated with
      convulsant activity. The active component of picrotoxin, picrotoxinin, was used
      as a control. While picrotoxinin did not differentiate well between 13 GABAA
      receptors, TETS exhibited the highest activity on alpha2beta3gamma2 (IC50 480 nM,
      95% CI 320-640 nM) and alpha6beta3gamma2 (IC50 400 nM, 95% CI 290-510 nM).
      Introducing beta1 or beta2 subunits into these receptor combinations reduced or
      abolished TETS sensitivity, suggesting that TETS preferentially affects receptors
      with alpha2/beta3 or alpha6/beta3 composition. Since alpha2beta3gamma2 receptors
      make up 15-20% of the GABAA receptors in the mammalian CNS, we suggest that
      alpha2beta3gamma2 is probably the most important GABAA receptor for the seizure
      inducing activity of TETS.

PMID- 29038842
TI  - Fertility after recurrent miscarriages: results of an observational cohort study.
AB  - PURPOSE: Recurrent pregnancy losses (RPL) are considered a pathological condition
      associated with heterogeneous laboratory and clinical findings, and are also
      linked to subfertility. We attempt to rank parameters derived from past history
      and diagnostic results with regard to the prognosis. METHODS: Observational trial
      on 719 consecutive couples who were referred to a tertiary immunological care
      centre (2006-2014) after three or more primary miscarriages. Information on past
      obstetric history and diagnostic procedures at baseline were correlated with
      cumulative pregnancy and delivery rates using Kaplan-Meier estimation, logistic
      regression and multivariate analysis. RESULTS: At baseline, median female age was
      34.1 years, waiting time 3 years (1-17), number of preceding miscarriages 3 (3
      9), 147 women (20.4%) had conceived at least once in ART or AIH cycles. After a
      median follow-up of 33.7 (1.7-123.0) months, 5-year pregnancy and delivery rates
      were 86.1 and 64.5%. Female age (< 35 years), waiting time (< 3 years) until
      baseline, tubal competence, and male factor fertility significantly correlated
      with favourable outcome (p < 0.001), while body mass index (> 29 kg/m2), number
      of preceding miscarriages (> 4), late miscarriages, preclinical losses and
      smoking revealed non-significant negative trends. Mode of conception until
      baseline (spontaneously or ART/AIH) and classification into idiopathic and non
      idiopathic RPL showed no prognostic relevance. CONCLUSION: Although in general,
      chances to conceive a child are retained after three or more miscarriages,
      factors related to subfertility of both partners have an important impact on the
      outcome. Therefore, prolonged time to pregnancy (> 6-9 months) should result in
      preventive gynaecological care from the first miscarriage on, so that fertility
      can be preserved as best as possible.

PMID- 29038843
TI  - Per-oral endoscopic salpingo-oophorectomy (POESY) in humans: a prospective
      clinical feasibility study.
AB  - BACKGROUND AND AIMS: Natural orifice translumenal endoscopic surgery (NOTES)
      procedure describes a surgical approach using natural orifices. We describe a
      prospective non-comparative clinical study on transgastric salpingo-oophorectomy
      in humans. METHODS: Patients with indication for salpingo-oophorectomy were
      offered the transgastric approach. This paper presents the data of the first 6
      patients, in whom the procedure was performed. After gastroscopic incision in the
      anterior corpus wall we advanced the flexible gastroscope into the abdominal
      cavity. With the help of a transvaginally introduced 10 mm trocar and, if the
      uterus was present, an intrauterine manipulator, the salpingo-oophorectomy was
      performed. The colpotomy was dilated and the specimens were extracted in a bag.
      The gastrotomy was closed with an over-the-scope-clip and the colpotomy with a
      running suture. RESULTS: The planned salpingo-oophorectomy was performed
      successfully in all patients. All patients recovered quickly and were discharged
      between the third and fifth day. In one patient a gastric bleeding was seen on
      the first postoperative day. The bleeding was clipped gastroscopically, all other
      follow ups were uneventful. CONCLUSION: Our study demonstrates the feasibility of
      the transgastric access to the pelvis. The gastroscope provided excellent optical
      control and good tissue preparation. Therefore, we conclude that pure NOTES
      procedures using the transgastric access to the adnexa are feasible. An
      increasing role of transgastric procedures for diseases in the pelvic region can
      be expected in particular if new endoscopic platforms with better means of
      instrumentation and tissue management become available.

PMID- 29038841
TI  - The maternal microbiome during pregnancy and allergic disease in the offspring.
AB  - There is substantial epidemiological and mechanistic evidence that the increase
      in allergic disease and asthma in many parts of the world in part relates to
      changes in microbial exposures and diet acting via the composition and metabolic
      products of the intestinal microbiome. The majority of research in this field has
      focused on the gut microbiome during infancy, but it is increasingly clear that
      the maternal microbiome during pregnancy also has a key role in preventing an
      allergy-prone immune phenotype in the offspring. The mechanisms by which the
      maternal microbiome influences the developing fetal immune system include
      alignment between the maternal and infant regulatory immune status and
      transplacental passage of microbial metabolites and IgG. Interplay between
      microbial stimulatory factors such as lipopolysaccharides and regulatory factors
      such as short-chain fatty acids may also influence on fetal immune development.
      However, our understanding of these pathways is at an early stage and further
      mechanistic studies are needed. There are also no data from human studies
      relating the composition and metabolic activity of the maternal microbiome during
      pregnancy to the offspring's immune status at birth and risk of allergic disease.
      Improved knowledge of these pathways may inform novel strategies for tackling the
      increase in allergic disorders in the modern world.

PMID- 29038844
TI  - In Vitro Antioxidant, Antihemolytic, and Anticancer Activity of the Carotenoids
      from Halophilic Archaea.
AB  - Halophilic archaea represent a promising natural source of carotenoids. However,
      little information is available about the biological effects of carotenoids from
      halophilic archaea. In this study, the carotenoids produced by seven halophilic
      archaeal strains Halogeometricum rufum, Halogeometricum limi, Haladaptatus
      litoreus, Haloplanus vescus, Halopelagius inordinatus, Halogranum rubrum, and
      Haloferax volcanii were identified by ultraviolet/visible spectroscopy, thin
      layer chromatography, and high-performance liquid chromatography-tandem mass
      spectrometry. The C50 carotenoids bacterioruberin and its derivatives
      monoanhydrobacterioruberin and bisanhydrobacterioruberin were found to be the
      predominant carotenoids. The antioxidant capacities of the carotenoids from these
      strains were significantly higher than beta-carotene as determined by 1,1
      diphenyl-2-picrylhydrazyl radical scavenging assay. The antihemolytic activities
      of these carotenoid extracts against H2O2-induced hemolysis in mouse erythrocytes
      were 3.9-6.3 times higher than beta-carotene. A dose-dependent in vitro
      antiproliferative activity against HepG2 cells was observed for the extract from
      Hgm. limi, while that from Hpn. vescus exhibited a relatively high activity in a
      dose-independent manner. These results suggested that halophilic archaea could be
      considered as an alternative source of natural carotenoids with high antioxidant,
      antihemolytic, and anticancer activity.

PMID- 29038845
TI  - Clinical and sonographic evaluation of subpectoral biceps tenodesis with a dual
      suture anchor technique demonstrates improved outcomes and a low failure rate at
      a minimum 2-year follow-up.
AB  - INTRODUCTION: The purpose of this study was to evaluate the clinical outcomes and
      integrity of an open subpectoral biceps tenodesis using a dual suture anchor
      construct. MATERIALS AND METHODS: Patients with at least 2 years of follow-up
      were retrospectively evaluated for simple shoulder test (SST), American Shoulder
      and Elbow Surgeons (ASES) score, and visual analog scales (VAS) for pain,
      function and satisfaction. A physical exam assessed shoulder range of motion and
      elbow strength. Ultrasonography visualized construct integrity. RESULTS: Of 43
      eligible patients, 36 completed questionnaire evaluation and 22 completed an
      additional physical examination. Indications included superior labral anterior
      posterior (SLAP) lesions (4), partial thickness tears (6), instability (6), and
      tenosynovitis of the biceps tendon (20). Eighteen patients (50%) had an
      associated rotator cuff tear. Patient-reported outcomes improved pre- vs
      postoperatively: ASES score (45.4 vs 78.6, P < 0.001), SST (5.1 vs 9.6, P <
      0.001), pain-VAS (4.8 vs 2.0, P < 0.001), and function-VAS (4.9 vs 2.3, P <
      0.001). Satisfaction-VAS was 8.3 postoperatively. Patient-reported outcomes did
      not differ for patients with an associated rotator cuff tear compared to those
      without (P >= 0.427). None of the physical exam measures were lower on the
      operative side compared to the healthy side (P >= 0.516). Sonographic evaluation
      revealed preserved integrity of the tenodesis construct in all cases. No
      complications were noted. CONCLUSIONS: Subpectoral biceps tenodesis utilizing a
      dual suture anchor technique is a treatment option for SLAP lesions, partial
      thickness tears, subluxation, and tenosynovitis of the long head of the biceps
      with high rates of postoperative patient satisfaction, a low failure rate, and
      improved outcome scores. The presence of a concomitant rotator cuff tear did not
      influence clinical outcomes.

PMID- 29038846
TI  - A possible implication of reduced levels of LIF, LIFR, and gp130 in vasculopathy
      related to systemic sclerosis.
AB  - Leukemia inhibitory factor (LIF) is a member of IL-6 family, which serves as a
      potent chemoattractant for neutrophils as well as a potent angiostatic factor.
      LIF has been implicated in various autoimmune inflammatory diseases, but its role
      still remains elusive in systemic sclerosis (SSc). Therefore, we investigated the
      potential role of LIF in the development of SSc by evaluating the clinical
      correlation of serum LIF levels, the expression of LIF and its receptors in skin
      samples, and in vitro experiments with human dermal microvascular endothelial
      cells. Serum LIF levels were significantly decreased in patients with SSc,
      especially in those with disease duration of < 1 year compared with healthy
      controls. As for clinical correlation, SSc patients with digital ulcers exhibited
      serum LIF levels significantly lower than those without. In immunohistochemistry,
      the expression of LIF and its receptors, LIF receptor and gp130, was remarkably
      decreased in dermal blood vessels of SSc lesional skin relative to those of
      healthy control skin. Furthermore, gene silencing of transcription factor Fli1,
      whose deficiency is involved in the development of SSc vasculopathy, suppressed
      the expression of LIF, LIF receptor, and gp130 and Fli1 bound to the promoters of
      those genes in human dermal microvascular endothelial cells. Collectively, these
      results suggest that decreased serum LIF levels may be associated with
      vasculopathy in SSc and that Fli1 deficiency may contribute to the inhibition of
      LIF-dependent biological effects on SSc endothelial cells by suppressing the
      expression of LIF, LIF receptor, and gp130.

PMID- 29038848
TI  - CA19-9 kinetics during systemic chemotherapy in patients with advanced or
      recurrent biliary tract cancer.
AB  - PURPOSE: The role of carbohydrate antigen 19-9 (CA19-9) kinetics in patients with
      biliary tract cancer (BTC) receiving chemotherapy remains to be elucidated.
      METHODS: A total of 185 advanced or recurrent BTC patients receiving a first line
      chemotherapy between January 2006 and March 2016, were retrospectively studied.
      Serum CA19-9 was measured at baseline and after two cycles of chemotherapy, and
      patients were categorized based on CA19-9 response: CA19-9 decrease group (>= 30%
      decrease), stable group (< 30% decrease and < 20% increase) and increase group
      (>= 20% increase). The associations of CA19-9 response with radiological tumor
      response, progression-free survival (PFS) and overall survival (OS) were
      investigated. RESULTS: There was a statistically significant association between
      CA19-9 response and radiological tumor responses (p < 0.001). The median PFS and
      OS were significantly different among three groups according to CA19-9 response:
      PFS of 8.0, 5.7 and 3.5 months in CA19-9 decrease, stable and increase groups (p
      < 0.001) and OS of 18.8, 16.0 and 7.5 months in CA19-9 decrease, stable and
      increase groups, respectively (p < 0.001). Multivariate analyses showed that CA19
      9 response was prognostic both of OS and PFS in addition, to CA19-9 at baseline,
      and performance status. CONCLUSION: CA19-9 kinetics after the first two cycles of
      a first line chemotherapy was a prognostic factor for OS and PFS in patients with
      advanced and recurrent BTC.

PMID- 29038847
TI  - Touching lips and hearing fingers: effector-specific congruency between tactile
      and auditory stimulation modulates N1 amplitude and alpha desynchronization.
AB  - Understanding the interactions between audition and sensorimotor processes is of
      theoretical importance, particularly in relation to speech processing. Although
      one current focus in this area is on interactions between auditory perception and
      the motor system, there has been less research on connections between the
      auditory and somatosensory modalities. The current study takes a novel approach
      to this omission by examining specific auditory-tactile interactions in the
      context of speech and non-speech sound production. Electroencephalography was
      used to examine brain responses when participants were presented with speech
      syllables (a bilabial sound /pa/ and a non-labial sound /ka/) or finger-snapping
      sounds that were simultaneously paired with tactile stimulation of either the
      lower lip or the right middle finger. Analyses focused on the sensory-evoked N1
      in the event-related potential and the extent of alpha band desynchronization
      elicited by the stimuli. N1 amplitude over fronto-central sites was significantly
      enhanced when the bilabial /pa/ sound was paired with tactile lip stimulation and
      when the finger-snapping sound was paired with tactile stimulation of the finger.
      Post-stimulus alpha desynchronization at central sites was also enhanced when the
      /pa/ sound was accompanied by tactile stimulation of the lip. These novel
      findings indicate that neural aspects of somatosensory-auditory interactions are
      influenced by the congruency between the location of the bodily touch and the
      bodily origin of a perceived sound.

PMID- 29038850
TI  - A triplet combination with capecitabine/oxaliplatin/irinotecan (XELOXIRI) plus
      cetuximab as first-line therapy for patients with metastatic colorectal cancer: a
      dose escalation study.
AB  - PURPOSE: The addition of cetuximab to triplet chemotherapy can increase treatment
      efficacy for patients with metastatic colorectal cancer (mCRC). We explored the
      dose-limiting toxicity and feasibility of a triweekly capecitabine, oxaliplatin,
      irinotecan, plus cetuximab (XELOXIRI plus cetuximab) regimen in patients with
      wild-type KRAS mCRC. METHODS: Patients received oxaliplatin (100 mg/m2, day 1),
      capecitabine (1700 mg/m2 per day from day 2 to 15), irinotecan (100, 120, and 150
      mg/m2 for dose levels 1, 2, 3, respectively, on day 1), and cetuximab (400 mg/m2,
      day 1 and, thereafter, 250 mg/m2 every week), repeated every 3 weeks. Dose
      limiting toxicities (DLTs) were assessed in the first 2 treatment cycles to
      determine the maximum tolerated dose (MTD) and the recommended dose (RD).
      RESULTS: Twelve patients received a median of 7 cycles of therapy (range 2-10).
      The DLT was grade 4 neutropenia, observed in 1 of 6 patients at dose level 2. The
      MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined
      as 150 mg/m2. Most common grade >= 3 toxicities were neutropenia (50%), diarrhea
      (17%), and febrile neutropenia (8%). The response rate was 83% (complete and
      partial response: 1 and 9 patient(s), respectively), including 4 conversion
      cases. CONCLUSIONS: The combination of XELOXIRI and cetuximab is feasible and has
      an acceptable toxicity profile; neutropenia was the DLT. The RD of irinotecan is
      150 mg/m2. The observed response rate was promising and warrants further
      investigation.

PMID- 29038849
TI  - Malignant bone tumors (other than Ewing's): clinical practice guidelines for
      diagnosis, treatment and follow-up by Spanish Group for Research on Sarcomas
      (GEIS).
AB  - Primary malignant bone tumors are uncommon and heterogeneous malignancies. This
      document is a guideline developed by the Spanish Group for Research on Sarcoma
      with the participation of different specialists involved in the diagnosis and
      treatment of bone sarcomas. The aim is to provide practical recommendations with
      the intention of helping in the clinical decision-making process. The diagnosis
      and treatment of bone tumors requires a multidisciplinary approach, involving as
      a minimum pathologists, radiologists, surgeons, and radiation and medical
      oncologists. Early referral to a specialist center could improve patients'
      survival. The multidisciplinary management of osteosarcoma, chondrosarcoma,
      chordoma, giant cell tumor of bone and other rare bone tumors is reviewed in this
      guideline. Ewing's sarcoma will be the focus of a separate guideline because of
      its specific biological, clinical and therapeutic features. Each statement has
      been accompanied by the level of evidence and grade of recommendation on the
      basis of the available data. Surgical excision is the mainstay of treatment of a
      localized bone tumor, with various techniques available depending on the
      histologic type, grade and location of the tumor. Chemotherapy plays an important
      role in some chemosensitive subtypes (such as high-grade osteosarcoma). In other
      subtypes, historically considered chemoresistant (such as chordoma or giant cell
      tumor of bone), new targeted therapies have emerged recently, with a very
      significant efficacy in the case of denosumab. Radiation therapy is usually
      necessary in the treatment of chordoma and sometimes of other bone tumors.

PMID- 29038852
TI  - The role of Journal of Anesthesia as a flagship anesthesia journal in Asia.

PMID- 29038851
TI  - Three cases of implantation of a SureScan(r) system and MRI for investigating
      causes of pain.
AB  - We report three cases of implantation of the SureScan(r) system and magnetic
      resonance imaging (MRI) for investigating causes of pain. Although there were
      metal-induced artifacts on the MR images of 2 patients, the artifacts did not
      affect the images of structures that needed to be assessed to make the diagnosis.
      The SureScan(r) system enabled patients implanted with spinal cord stimulation
      devices to undergo MRI.

PMID- 29038853
TI  - Arterial-ventricular coupling in type 1 diabetes: arterial stiffness is
      associated with impaired global longitudinal strain in type 1 diabetes patients
      the Thousand & 1 Study.
AB  - AIMS: Diabetes is associated with higher arterial stiffness-an early marker of
      cardiovascular disease. The coupling between arterial stiffness and myocardial
      function is still unresolved. We investigate associations between arterial
      stiffness and early myocardial impairment assessed with advanced
      echocardiography. METHODS: In 305 type 1 diabetes (T1D) patients without known
      heart disease and with normal left ventricular ejection fraction (LVEF) (biplane
      LVEF > 45%), we measured arterial stiffness as pulse wave velocity (PWV) and
      performed conventional and speckle-tracking echocardiography assessing global
      longitudinal strain (GLS) as a measure of systolic myocardial function.
      Associations between PWV and myocardial function were reported as standardized
      beta values from adjusted regression models including age, sex, mean arterial
      pressure, body mass index, HbA1c, diabetes duration, estimated glomerular
      filtration rate, degree of albuminuria, total cholesterol, heart rate and
      smoking. RESULTS: Patients were 54 (12) years [mean (SD)], 152 (50%) females,
      diabetes duration 31 (16) years, HbA1c 65 (12) mmol/mol, LVEF 58 (5) %, GLS -18.2
      (2.6) % and PWV 10.2 (3.4) m/s. There was no association between PWV and LVEF (p
      = 0.93). Conversely, there was a highly significant association between PWV and
      GLS in crude and multivariable models (standardized beta-coefficient 0.25, p <
      0.001 and 0.16, p = 0.036, respectively). Also, diastolic function measured as
      E/e' was highly associated with PWV in crude and multivariable models
      (standardized beta-coefficient 0.43, p < 0.001 and 0.17, p = 0.016,
      respectively). CONCLUSIONS: In T1D patients with normal LVEF and without known
      heart disease, higher arterial stiffness is independently associated with early
      systolic and diastolic myocardial impairment detectable by advanced
      echocardiography. Although unable to demonstrate causality, we display a
      relationship between diabetic angiopathy and diabetic cardiomyopathy (H-3-2009
      139 and PROFIL-H-B-2009-056).

PMID- 29038854
TI  - Who is a survivor? Perceptions from individuals who experienced pediatric cancer
      and their primary support persons.
AB  - PURPOSE: The purpose of this research was to examine the lived experiences of
      individuals who had cancer as children, as well as lived experiences of their
      current primary support persons. METHODS: Based on van Manen's "new" interpretive
      phenomenology, interviews were conducted with ten pediatric cancer survivors and
      nine of their support persons to gain a more holistic understanding of the
      pediatric cancer experiences of children and their families. RESULTS: Four themes
      emerged from the data; however, only the topic of the use of the term "survivor"
      and identification with the term will be discussed. All participants in the study
      described their personal definition of the term survivor and what it meant to be
      a survivor. Additionally, all individuals in the study discussed the concept of
      being a survivor and if they would consider themselves, or their loved ones, to
      be "survivors." CONCLUSIONS: The results of this study provide health care
      professionals, family members, and individuals fundraising or advocating for
      cancer causes with insights on how the term survivor may be interpreted. This
      study may provide insight to individuals who had cancer as children, in showing
      that their personal perspective shapes their identity; although "survivor" is
      common cancer vernacular, individuals can choose not to identify with their
      illness experiences.

PMID- 29038855
TI  - Imaging mimics of pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma is the most common primary malignancy of the
      pancreas. The classic imaging features are a hypovascular mass with proximal
      ductal dilatation. Different pancreatic pathologies can mimic the imaging
      appearance of carcinoma including other tumors involving the pancreas (pancreatic
      neuroendocrine tumors, lymphoma, metastasis, and rare tumors like pancreatic
      acinar cell carcinoma and solid pseudopapillary tumors), inflammatory processes
      (chronic pancreatitis and autoimmune pancreatitis), and anatomic variants
      (annular pancreas). Differentiation between these entities can sometimes be
      challenging due to overlap of imaging features. The purpose of this article is to
      describe the common entities that can mimic pancreatic cancer on imaging with
      illustrative examples and to suggest features that can help in differentiation of
      these entities.

PMID- 29038856
TI  - Comparison of diagnostic performance between 1 millisievert CT enterography and
      half-standard dose CT enterography for evaluating active inflammation in patients
      with Crohn's disease.
AB  - PURPOSE: To compare the diagnostic performance of CT enterography (CTE) images
      obtained at 1 millisievert (mSv) and reconstructed with filtered back projection
      (FBP) and adaptive statistical iterative reconstruction (ASIR) with those of half
      dose CTE images for the evaluation of active inflammation in patients with
      Crohn's disease. METHODS: Forty-six consecutive patients (mean age 29 years;
      range 15-59 years) with Crohn's disease underwent CTE which comprised a standard
      dose scan at the enteric phase (45 s), a half-dose scan with ASIR at the portal
      venous phase (70 s), and 1 mSv scans with FBP and ASIR at the delayed phase (90
      s) under a fixed 120 kVp and variable mAs. Two blinded readers independently
      recorded confidence scores for active inflammation in the ileum and terminal
      ileum, respectively. The diagnostic performance of each image set was compared by
      pairwise comparison of receiver operating characteristic curves. The established
      image findings on standard-dose scan and ileocolonoscopy served as the reference
      standard. RESULTS: A total of 92 bowel segments were analyzed. For reader 1, the
      diagnostic performance was increased from 1 mSv CT with FBP and 1 mSv CT with
      ASIR to half-dose scan with ASIR (AUC, 0.759, 0.794, and 0.845; P = 0.1429, P =
      0.0107, respectively). For reader 2, there was no significant difference among
      the three image sets (AUC, 0.848, 0.865, and 0.845; P > 0.05, respectively).
      CONCLUSIONS: The diagnostic performance of 1 mSv CTE may be comparable to that of
      half-dose CTE.

PMID- 29038857
TI  - LI-RADS categories: concepts, definitions, and criteria.
AB  - The Liver Imaging Reporting and Data System (LI-RADS) was created to provide a
      standardized way to both assess and communicate the likelihood of benignity or
      malignancy of observations seen in patients at risk for development of
      hepatocellular carcinoma (HCC). The LI-RADS categories allow radiologists to
      convey the full spectrum of concern for malignancy, from definitely benign to
      definitely HCC. Additional categories are available for non-categorizable
      observations, observations that are concerning for a non-HCC malignancy, and the
      presence of tumor in vein. The goal of this paper is to discuss the LI-RADS
      categories, including criteria for each category, and point out changes to the
      categories from prior versions of LI-RADS.

PMID- 29038858
TI  - Surgical management of primary hyperparathyroidism.
AB  - We reviewed the surgical management of primary hyperparathyroidism through a
      retrospective chart review of 200 parathyroidectomy procedures performed over a
      12 year period. Epidemiological data and accuracy of radiological investigations
      used in identifying pathological parathyroid tissue location were assessed. We
      determined how often simultaneous removal of thyroid tissue was required during
      parathyroidectomy and the associated pathology. Radiology reports were screened
      to determine if confirmed thyroid pathology from histological specimens were
      referenced pre-operatively. Open parathyroid surgery was performed in 71%, the
      remainder endoscopically. 95% of parathyroid specimens were confirmed as benign
      adenomas, with eight cases of hyperplasia and two parathyroid carcinomas. Pre
      operative ultrasound and SPECT-CT imaging demonstrated sensitivity of 55% and 73%
      respectively with regards correct adenoma localisation. Forty-nine patients (25%)
      underwent simultaneous partial thyroidectomy, 45 (92%) with dual pathology
      confirmed. Malignant thyroid lesions were identified in 18% (n = 8), Graves'
      disease 2% (n = 1), thyroiditis 9% (n = 4), multinodular goitre 56% (n = 25),
      unilateral nodule 4% (n = 2), hyperplasia 7% (n = 3) and intra-thyroid adenoma 4%
      (n = 2). Reference to these thyroid lesions was made in only 36% of preoperative
      imaging reports. In conclusion, synchronous thyroid surgery was carried out in a
      quarter of all parathyroidectomy procedures performed for treatment of primary
      hyperparathyroidism. Coincidental thyroid pathology was common. The limitations
      of pre-operative imaging in reliably locating involved parathyroid tissue are
      demonstrated and the importance of considering the potential need to perform
      thyroid surgery during parathyroidectomy and obtaining appropriate informed
      consent.

PMID- 29038860
TI  - The role of subtotal petrosectomy in cochlear implant recipients.
AB  - Describe the indications and outcome of subtotal petrosectomy for cochlear
      implant recipients. Tertiary care referral center. This is a retrospective study
      of all subtotal petrosectomies and cochlear implants performed between January
      2012 and December 2014. We review the charts of these patients collecting the
      following data: age, gender, otologic history, audiologic tests, indication of
      subtotal petrosectomy, data of surgery, surgical and immediate complications,
      late complications and follow-up of for at least 2.5 years. 12 cases of subtotal
      petrosectomies with cochlear implantation in 11 patients were performed during
      this period; 2 children and 10 adults. The indication for a cochlear implant was
      in 10 cases bilateral severe to profound sensorineural hearing loss and in the
      remaining 2 cases was asymmetric hearing loss or unilateral hearing loss. The
      reason for performing a subtotal petrosectomy was chronic otitis media with or
      without cholesteatoma, radical cavities from previous surgeries or electrode
      extrusion of previously implanted devices. All cases were performed in one stage.
      One patient had an infectious complication that required revision surgery and
      finally an explantation. No other complications are described. Subtotal
      petrosectomy combined with cochlear implantation is a procedure required in
      certain situations. It is an effective and safe procedure for managing middle ear
      problems and creating a safe cavity to receive a cochlear implant either in
      adults and children.

PMID- 29038859
TI  - Refashioned lamb tissue as an animal model for training complex techniques of
      laryngotracheal stenosis surgery.
AB  - Open reconstructive upper airway surgery for laryngotracheal stenosis (LTS),
      whether for subglottic or tracheal stenosis, constitutes a group of complex
      approaches. LTS requiring open reconstruction is overall rare and primarily
      performed at tertiary centres. This poses an obvious challenge for the
      acquisition and maintenance of surgical skills for this group of complex
      approaches. In this context, animal models provide a unique opportunity for open
      reconstructive airway surgery training. Such models ought to take into
      consideration ethical aspects, be easily available and easy to maintain, and have
      similar macroscopic anatomical features to the human laryngotracheal frame. Here,
      we provide a brief surgical guide for the use of refashioned lamb tissue as a
      training model for surgery of adult and pediatric reconstructive airway surgery.
      The techniques of laryngotracheal reconstruction, partial cricotracheal
      resection, tracheal resection with end-to-end anastomosis, and slide
      tracheoplasty are presented. Proper training in open LTS surgery is challenging,
      time consuming and its complexity further lengthens the learning curve. The lamb
      larynx and trachea model is an effective model for practising various airway
      reclaiming surgeries.

PMID- 29038861
TI  - Drier climate shifts leaf morphology in Amazonian trees.
AB  - The humid forests of Amazonia are experiencing longer and more intense dry
      seasons, which are predicted to intensify by the end of the 21st century.
      Although tree species often have long generation times, they may still have the
      capacity to rapidly respond to changing climatic conditions through adaptive
      phenotypic plasticity. We, therefore, predicted that Amazonian trees have shifted
      their leaf morphology in response to the recent drier climate. We tested this
      prediction by analysing historical herbarium specimens of six Amazonian tree
      species collected over a 60-year period and comparing changes in leaf morphology
      with historical precipitation data. Moreover, we explored spatial and temporal
      biases in herbarium specimens and accounted for their potentially confounding
      effect in our analysis. We found pronounced biases in herbarium specimens, with
      nearly 20% of specimens collected in close geographic proximity and around the
      1975s. When accounting for such biases, our results indicate a trend of
      decreasing leaf size after the 1970s, which may have been spurred by an observed
      reduction in rainfall. Our findings support the hypothesis that (some) Amazonian
      trees have the capacity to adaptively change their leaf phenotypes in response to
      the recent drier climate. Nevertheless, the unavoidable spatial and temporal
      biases in herbarium specimens call for caution when generalizing our findings to
      all Amazonian trees.

PMID- 29038862
TI  - Examining spatial patterns of selection and use for an altered predator guild.
AB  - Anthropogenic disturbances have altered species' distributions potentially
      impacting interspecific interactions. Interference competition is when one
      species denies a competing species access to a resource. One mechanism of
      interference competition is aggression, which can result in altered space-use of
      a subordinate species due to the threat of harm, otherwise known as a 'landscape
      of fear'. Alternatively, subordinates might outcompete dominant species in
      resource-poor environments via a superior ability to extract resources. Our goal
      was to evaluate spatial predictions of the 'landscape of fear' hypothesis for a
      carnivore guild in Newfoundland, Canada, where coyotes recently immigrated.
      Native Newfoundland carnivores include red foxes, Canada lynx, and black bears.
      We predicted foxes and lynx would avoid coyotes because of their larger size and
      similar dietary niches. We used scat-detecting dogs and genetic techniques to
      locate and identify predator scats. We then built resource selection functions
      and tested for avoidance by incorporating predicted values of selection for the
      alternative species into the best supported models of each species. We found
      multiple negative relationships, but notably did not find avoidance by foxes of
      areas selected by coyotes. While we did find that lynx avoided coyotes, we also
      found a reciprocal relationship. The observed patterns suggest spatial
      partitioning and not coyote avoidance, although avoidance could still be
      occurring at different spatial or temporal scales. Furthermore, Newfoundland's
      harsh climate and poor soils may swing the pendulum of interspecific interactions
      from interference competition to exploitative competition, where subordinates
      outcompete dominant competitors through a superior ability to extract resources.

PMID- 29038863
TI  - A warmer and drier climate in the northern sagebrush biome does not promote
      cheatgrass invasion or change its response to fire.
AB  - Dryland shrub communities have been degraded by a range of disturbances and now
      face additional stress from global climate change. The spring/summer growing
      season of the North American sagebrush biome is projected to become warmer and
      drier, which is expected to facilitate the expansion of the invasive annual grass
      Bromus tectorum (cheatgrass) and alter its response to fire in the northern
      extent of the biome. We tested these predictions with a factorial experiment with
      two levels of burning (spring burn and none) and three climate treatments
      (warming, warming + drying, and control) that was repeated over 3 years in a
      Montana sagebrush steppe. We expected the climate treatments to make B. tectorum
      more competitive with the native perennial grass community, especially
      Pseudoroegneria spicata, and alter its response to fire. Experimental warming and
      warming + drying reduced B. tectorum cover, biomass, and fecundity, but there was
      no response to fire except for fecundity, which increased; the native grass
      community was the most significant factor that affected B. tectorum metrics. The
      experimental climate treatments also negatively affected P. spicata, total native
      grass cover, and community biodiversity, while fire negatively affected total
      native grass cover, particularly when climate conditions were warmer and drier.
      Our short-term results indicate that without sufficient antecedent moisture and a
      significant disruption to the native perennial grass community, a change in
      climate to a warmer and drier spring/summer growing season in the northern
      sagebrush biome will not facilitate B. tectorum invasion or alter its response to
      fire.

PMID- 29038865
TI  - Multinodular and vacuolating neuronal tumor in an adolescent with Klinefelter
      syndrome.

PMID- 29038864
TI  - Improved detection of genetic loci in estimated glomerular filtration rate and
      type 2 diabetes using a pleiotropic cFDR method.
AB  - Genome-wide association studies (GWAS) have been shown to have the potential of
      explaining more of the "missing heritability" of complex human phenotypes by
      improving statistical approaches. Here, we applied a genetic-pleiotropy-informed
      conditional false discovery rate (cFDR) to capture additional polygenic effects
      associated with estimated glomerular filtration rate (creatinine) (eGFRcrea) and
      type 2 diabetes (T2D). The cFDR analysis improves the identification of
      pleiotropic variants by incorporating potentially shared genetic mechanisms
      between two related traits. The Q-Q and fold-enrichment plots were used to assess
      the enrichment of SNPs associated with eGFRcrea or T2D, and Manhattan plots were
      used for showing chromosomal locations of the significant loci detected. By
      applying the cFDR method, we newly identified 74 loci for eGFRcrea and 3 loci for
      T2D with the cFDR criterion of 0.05 compared with previous related GWAS studies.
      Four shared SNPs were detected to be associated with both eGFRcrea and T2D at the
      significant conjunction cFDR level of 0.05, and these shared SNPs had not been
      reported in previous studies. In addition, we used DAVID analysis to perform
      functional analysis of the shared SNPs' annotated genes and found their potential
      hidden associations with eGFRcrea and T2D. In this study, the cFDR method shows
      the feasibility to detect more genetic variants underlying the heritability of
      eGFRcrea and T2D, and the overlapping SNPs identified could be regarded as
      candidate loci that provide a thread of genetic mechanisms between eGFRcrea and
      T2D in future research.

PMID- 29038866
TI  - Complete genome sequence of a novel avian paramyxovirus isolated from wild birds
      in South Korea.
AB  - A novel avian paramyxovirus (APMV), Cheonsu1510, was isolated from wild bird
      feces in South Korea and serologically and genetically characterized. In
      hemagglutination inhibition tests, antiserum against Cheonsu1510 showed low
      reactivity with other APMVs and vice versa. The complete genome of Cheonsu1510
      comprised 15,408 nucleotides, contained six open reading frames (3'-N-P-M-F-HN-L
      5'), and showed low sequence identity to other APMVs (< 63%) and a unique genomic
      composition. Phylogenetic analysis revealed that Cheonsu1510 was related to but
      distinct from APMV-1, -9, and -15. These results suggest that Cheonsu1510
      represents a new APMV serotype, APMV-17.

PMID- 29038867
TI  - Correction to: Transethnic insight into the genetics of glycaemic traits: fine
      mapping results from the Population Architecture using Genomics and Epidemiology
      (PAGE) consortium.
AB  - The authors regret that Yinchang Lu's name incorrectly included a middle initial
      in the author list. The details given in this erratum are correct.

PMID- 29038869
TI  - Expert's comment concerning Grand Rounds case entitled "Management of a high
      thoracic Chance Fracture" by A. Bourghli et al. (Eur Spine J; 2017.
      doi:10.1007/s00586-017-5247-8).

PMID- 29038868
TI  - The Global Spine Care Initiative: a review of reviews and recommendations for the
      non-invasive management of acute osteoporotic vertebral compression fracture pain
      in low- and middle-income communities.
AB  - PURPOSE: The purpose of this review was to develop recommendations for non
      invasive management of pain due to osteoporotic vertebral compression fractures
      (OVCF) that could be applied in medically underserved areas and low- and middle
      income countries. METHODS: We conducted a systematic review and best evidence
      synthesis of systematic reviews on the non-invasive management of OVCF. Eligible
      reviews were critically appraised using the Scottish Intercollegiate Guidelines
      Network criteria. Low risk of bias systematic reviews and high-quality primary
      studies that were identified in the reviews were used to develop recommendations.
      RESULTS: From 6 low risk of bias systematic reviews and 14 high-quality primary
      studies we established that for acute pain management, in addition to rest and
      analgesic medication, orthoses may provide temporary pain relief, in addition to
      early mobilization. Calcitonin can be considered as a supplement to analgesics;
      however, cost is of concern. Once acute pain control is achieved, exercise can be
      effective for improving function and quality of life. CONCLUSION: The findings
      from this study will help to inform the GSCI care pathway and model of care for
      use in medically underserved areas and low- and middle-income countries.
      Conservative management of acute pain and recovery of function in adults with
      OVCF should include early mobilization, exercise, spinal orthosis for pain
      relief, and calcitonin for analgesic-refractory acute pain. These slides can be
      retrieved under Electronic Supplementary Material.

PMID- 29038870
TI  - Chiropractic care and risk for acute lumbar disc herniation: a population-based
      self-controlled case series study.
AB  - PURPOSE: Chiropractic care is popular for low back pain, but may increase the
      risk for acute lumbar disc herniation (LDH). Low back pain is a common early
      (prodromal) symptom of LDH and commonly precedes LDH diagnosis. Our objective was
      to investigate the association between chiropractic care and acute LDH with early
      surgical intervention, and contrast this with the association between primary
      care physician (PCP) care and acute LDH with early surgery. METHODS: Using a self
      controlled case series design and population-based healthcare databases in
      Ontario, Canada, we investigated all adults with acute LDH requiring emergency
      department (ED) visit and early surgical intervention from April 1994 to December
      2004. The relative incidence of acute LDH with early surgery in exposed periods
      after chiropractic visits relative to unexposed periods was estimated within
      individuals, and compared with the relative incidence of acute LDH with early
      surgery following PCP visits. RESULTS: 195 cases of acute LDH with early surgery
      (within 8 weeks) were identified in a population of more than 100 million person
      years. Strong positive associations were found between acute LDH and both
      chiropractic and PCP visits. The risk for acute LDH with early surgery associated
      with chiropractic visits was no higher than the risk associated with PCP visits.
      CONCLUSIONS: Both chiropractic and primary medical care were associated with an
      increased risk for acute LDH requiring ED visit and early surgery. Our analysis
      suggests that patients with prodromal back pain from a developing disc herniation
      likely seek healthcare from both chiropractors and PCPs before full clinical
      expression of acute LDH. We found no evidence of excess risk for acute LDH with
      early surgery associated with chiropractic compared with primary medical care.

PMID- 29038871
TI  - The Global Spine Care Initiative: a consensus process to develop and validate a
      stratification scheme for surgical care of spinal disorders as a guide for
      improved resource utilization in low- and middle-income communities.
AB  - PURPOSE: The purpose of this study was to develop a stratification scheme for
      surgical spinal care to serve as a framework for referrals and distribution of
      patients with spinal disorders. METHODS: We used a modified Delphi process. A
      literature search identified experts for the consensus panel and the panel was
      expanded by inviting spine surgeons known to be global opinion leaders. After
      creating a seed document of five hierarchical levels of surgical care, a four
      step modified Delphi process (question validation, collection of factors,
      evaluation of factors, re-evaluation of factors) was performed. RESULTS: Of 78
      invited experts, 19 participated in round 1, and of the 19, 14 participated in 2,
      and 12 in 3 and 4. Consensus was fairly heterogeneous for levels of care 2-4
      (moderate resources). Only simple assessment methods based on the clinical skills
      of the medical personnel were considered feasible and safe in low-resource
      settings. Diagnosis, staging, and treatment were deemed feasible and safe in a
      specialized spine center. Accurate diagnostic workup was deemed feasible and safe
      for lower levels of care complexity (from level 3 upwards) compared to non
      invasive procedures (level 4) and the full range of invasive procedures (level
      5). CONCLUSION: This study introduces a five-level stratification scheme for the
      surgical care of spinal disorders. This stratification may provide input into the
      Global Spine Care Initiative care pathway that will be applied in medically
      underserved areas and low- and middle-income countries. These slides can be
      retrieved under Electronic Supplementary Material.

PMID- 29038874
TI  - Ultrasound-Guided Popliteal Sciatic Block Provides Adequate Analgesia During
      Urgent Endovascular Treatment of Critical Limb Ischemia with Resting Pain.
AB  - PURPOSE: To demonstrate feasibility and safety of ultrasound-guided popliteal
      sciatic nerve block for providing analgesia during urgent endovascular treatment
      of critical limb ischemia with resting pain. MATERIALS AND METHODS: Ultrasound
      guided popliteal sciatic blocks were performed by an interventional radiologist
      in angiography suite immediately prior to commencement of urgent endovascular
      treatment of 30 critical limb ischemia patients. Subjective pain levels prior to
      and following sciatic block were assessed using the visual analog scale (VAS).
      Need for any supplemental anxiolytics or analgesics during treatment was
      recorded. Post-procedural evaluation of patient and operator satisfaction levels
      regarding the intervention was also documented. RESULTS: Ultrasound-guided
      sciatic block provided adequate analgesia in all patients; VAS scores were 0 (no
      pain) in 87% and 1-3 (mild to annoying pain) in 13%. Two patients required
      anxiolytic premedication. Additional analgesia was not required during course of
      endovascular treatment of any patients. Time necessary to perform sciatic block
      ranged 3-9 (mean 5.9 +/- 1.3) min. Median number of needle attempts was 1 (range
      1-3). Onset of satisfactory block ranged from 5 to 20 min (mean 9.4 +/- 2.6 min).
      Mean treatment time was 102.2 +/- 36.7 min, and balloon time was 22.4 +/- 6.1
      min. Patient and operator satisfaction with pain control were very good in all
      cases. There were no procedure-related complications. CONCLUSIONS: Ultrasound
      guided popliteal sciatic block is a feasible and safe alternative for providing
      adequate analgesia during urgent endovascular treatment of critical limb ischemia
      with resting pain. LEVEL OF EVIDENCE: Level 4, case series.

PMID- 29038872
TI  - A novel method to understand tumor cell invasion: integrating extracellular
      matrix mimicking layers in microfluidic chips by "selective curing".
AB  - A major challenge in studying tumor cell invasion into its surrounding tissue is
      to identify the contribution of individual factors in the tumor microenvironment
      (TME) to the process. One of the important elements of the TME is the fibrous
      extracellular matrix (ECM) which is known to influence cancer cell invasion, but
      exactly how remains unclear. Therefore, there is a need for new models to unravel
      mechanisms behind the tumor-ECM interaction. In this article, we present a new
      microfabrication method, called selective curing, to integrate ECM-mimicking
      layers between two microfluidic channels. This method enables us to study the
      effect of 3D matrices with controlled architecture, beyond the conventionally
      used hydrogels, on cancer invasion in a controlled environment. As a proof of
      principle, we have integrated two electrospun Polycaprolactone (PCL) matrices
      with different fiber diameters in one chip. We then studied the 3D migration of
      MDA-MB-231 breast cancer cells into the matrices under the influence of a
      chemotactic gradient. The results show that neither the invasion distance nor the
      general cell morphology is affected significantly by the difference in fiber size
      of these matrices. The cells however do produce longer and more protrusions in
      the matrix with smaller fiber size. This microfluidic system enables us to study
      the influence of other factors in the TME on cancer development as well as other
      biological applications as it provides a controlled compartmentalized environment
      compatible with cell culturing.

PMID- 29038875
TI  - Sclerotherapy for Rectal Varices by a Small-Bore Needle Puncture Through the
      Greater Sciatic Foramen.
AB  - PURPOSE: To report a sclerotherapy technique for rectal varices consisting of
      direct puncture of the superior rectal vein with a small-bore sheathed needle via
      the greater sciatic foramen without insertion of a sheath or catheter. MATERIALS
      AND METHODS: The subjects of this retrospective study were three consecutive
      patients who underwent embolization of rectal varices, two for rupture of rectal
      varices and one for hepatic encephalopathy and hyperammonemia. A 5% solution of
      ethanolamine oleate with iodinated contrast agent (5% EOI) was injected through
      puncture of the superior rectal vein and carried in the blood flow, after which n
      butyl cyanoacrylate mixed with lipiodol (NBCA-Lip) was immediately injected to
      stop the blood flow. RESULTS: The 5% EOI and NBCA-Lip were successfully injected
      in all three patients. There was no movement of NBCA-Lip on plain radiographs or
      computed tomography (CT) immediately after injection, and the 5% EOI remained
      within the rectal varices. The mean procedure time was 53 min (42-60 min). On
      contrast-enhanced CT 1 month after the procedure, there was no contrast
      enhancement of the rectal varices that had been seen on preoperative CT in any of
      the three patients, confirming that the rectal varices had disappeared.
      CONCLUSION: Sclerotherapy for rectal varices using an approach for puncture of
      the superior rectal vein with a small-bore sheathed needle via the greater
      sciatic foramen was technically feasible and clinically effective.

PMID- 29038876
TI  - Complications and Retrieval Data of Vena Cava Filters Based on Specific
      Infrarenal Location.
AB  - PURPOSE: Although recommended placement of IVC filters is with their tips
      positioned at the level of the renal vein inflow, in practice, adherence is
      limited due to clinical situation or IVC anatomy. We seek to evaluate the
      indwelling and retrieval complications of IVC filters based on their specific
      position within the infrarenal IVC. MATERIALS AND METHODS: Retrospective, single
      institution study of 333 consecutive infrarenal vena cava filters placed by
      interventional radiologists in patients with an average age of 62.2 +/- 15.7
      years was performed between 2013 and 2015. Primary indication was venous
      thromboembolic disease (n = 320, 96.1%). Filters were classified based on
      location of the apex below the lowest renal vein inflow on the procedural
      venogram: less than 1 cm (n = 180, 54.1%), 1-2 cm (n = 96, 28.8%), and greater
      than 2 cm (n = 57, 17.1%). Denali (n = 171, 51.4%) and Celect (n = 162, 48.6%)
      filters were evaluated. CT follow-up, indwelling complications, and retrieval
      data were obtained. RESULTS: Follow-up CT imaging performed for symptomatic
      indications occurred for 38.3% of filters placed < 1 cm below the lowest renal
      vein, 27.1% of filters placed 1-2 cm, and 36.8% placed > 2 cm (p = .16). There
      was no difference in caval strut penetration, penetration of adjacent viscera,
      time to penetration, filter migration, or tilt (p = .15, .27, .41, .57, .93). No
      filter fractures occurred. There was no difference in the incidence of
      breakthrough PE or complex filter retrieval (p = .83, .59). Only one retrieval
      failure occurred. CONCLUSIONS: This study suggests filter apex location within
      the infrarenal IVC, including placement > 2 cm below the level of the renal vein
      inflow, is not associated with differences in indwelling or retrieval
      complications. LEVEL OF EVIDENCE: Level 3 non-randomized controlled follow-up
      study.

PMID- 29038877
TI  - The Assessment of the Risk of Acute Kidney Injury in Patients Undergoing an
      Urgent Endovascular Treatment Due to Severe Renal Bleeding.
AB  - INTRODUCTION: This study was designed to assess the clinical factors associated
      with the development of acute kidney injury (AKI) in patients undergoing
      endovascular treatment during the course of severe renal bleeding. METHODS: A
      retrospective analysis was performed of 36 consecutive patients who were treated
      endovascularly between January 2006 and December 2016 for anemia caused by
      iatrogenic (26 pts) or posttraumatic (10 pts) renal bleeding. Typical patient
      data, baseline, and postprocedural blood parameters were evaluated. As a
      predictor of AKI occurrence, SCr0 > 1.5 mg/dL, eGFR < 60 ml/min/1.73 m2, and
      Mehran score were evaluated. RESULTS: Fourteen patients (39%) developed AKI after
      CM injection. Time of hospitalization (p = 0.02), hypotension (p = 0.005),
      dialysis (p = 0.05), blood transfusions (p = 0.028), amount of blood received (p
      = 0.003), red blood units > 3 (RBU) (p = 0.032), and CM > 150 ml (p = 0.014) were
      related to AKI occurrence. The Mehran score may be used as a predictor of AKI
      occurrence (p = 0.022). The SCr > 1.5 mg/dL and eGFR < 60 ml/min/1.73 m2 were not
      statistically significant. Selective renal embolization (mean 34% loss of renal
      tissue) does not lead to AKI. CONCLUSIONS: Hypotension, anemia requiring blood
      transfusion, and administration of CM exceeding 150 ml poses higher risk of AKI
      development, which leads to longer hospital stay and need of dialysis. The Mehran
      score may be used as predictor of AKI occurrence. Up to one third of the kidney
      was embolized with no AKI linked to the procedure. The concern of AKI occurrence
      should not be a cause of delay of endovascular treatment.

PMID- 29038878
TI  - Transjugular Intrahepatic Portosystemic Shunt Reduction Using the GORE VIATORR
      Controlled Expansion Endoprosthesis: Hemodynamics of Reducing an Established 10
      mm TIPS to 8-mm in Diameter.

PMID- 29038879
TI  - Acute Carotid Artery Stent Thrombosis.

PMID- 29038880
TI  - CT-Guided, Percutaneous Ethanol Sympatholysis for Primary Hyperhidrosis.
AB  - PURPOSE: Primary hyperhidrosis (PH) typically involves the craniofacial (CF) or
      axillary-palmar (AP) region. Our purpose was to determine the safety and efficacy
      of CT-guided sympatholysis for treating PH. METHODS: In this prospective study,
      39 consecutive patients with CF or AP PH were referred for percutaneous
      sympatholysis. Procedures were performed under CT guidance and minimal sedation.
      We treated level T2 for CF hyperhidrosis and T2, T3, and T4 for AP hyperhidrosis.
      Twenty-two-gauge spinal needles were placed bilaterally at the anterolateral
      surface of the vertebral body. After infiltration of lidocaine (2 mL), a
      neurological test was performed to exclude Horner syndrome. Neurolysis was
      effected with ethanol (2 mL) via each needle. Patients were discharged 1 h
      postoperatively and followed up at 1 week, 1 month, and then as clinically
      indicated. Disease-free Kaplan-Meier curves were compared using log-rank tests.
      Complications were categorized according to Common Terminology Criteria for
      Adverse Events. RESULTS: One patient failed the lidocaine test and was excluded.
      Of the 38 patients included in this cohort (16 men), mean age was 38 years (range
      18-61), and mean follow-up was 18 months (range 1-36). Technical success for
      these 38 patients was 100%. Seventeen patients had symptom recurrence, 14 of whom
      were retreated. Efficacy was 72% for CF hyperhidrosis, 50% for AP hyperhidrosis,
      and 60% overall. There were three major complications (two pneumothoraces, one
      severe intercostal neuralgia requiring medication). CONCLUSIONS: CT-guided
      sympatholysis for CF or AP PH had 18-month efficacy rates of 72 and 50%, with a
      favorable risk profile. LEVEL OF EVIDENCE: Level 2b.

PMID- 29038881
TI  - DownRegulated SOX4 Expression Suppresses Cell Proliferation, Migration, and
      Induces Apoptosis in Osteosarcoma In Vitro and In Vivo.
AB  - The SOX4 transcription factor is involved in various cellular processes, such as
      embryonic development and differentiation. Deregulated expression of Sox4 in
      several human cancers has been reported to date, but its biological functions in
      the progression of osteosarcoma remain unclear. In this study, we found that the
      expression levels of SOX4 protein were significantly higher in high-grade
      osteosarcoma tissues and metastatic osteosarcoma tissues. Its overexpression was
      associated with poor prognosis in osteosarcoma. Knockdown of the SOX4 gene in the
      osteosarcoma cell lines resulted in decreased cell proliferation, migration,
      invasion, and induced apoptosis. After SOX4 gene silencing, the protein
      expression levels of Bax, Caspase-3, and P53 in osteosarcoma cells were
      significantly elevated, while the protein expression levels of Bcl-2, MMP2, and
      MMP9 were obviously decreased. In vivo analysis in nude mice further confirmed
      that knockdown of SOX4 suppressed tumor growth. In conclusion, SOX4 appears to be
      an important tumor oncogene in the regulation of osteosarcoma cell proliferation,
      apoptosis, and invasion, and it may be a potential target for effective
      osteosarcoma therapy.

PMID- 29038884
TI  - [Progressive encephalomyelitis with rigidity and myoclonus : Stiff tongue as
      initial symptom].

PMID- 29038883
TI  - [Multiple sclerosis in childhood and adolescence : Complex, chronic and
      differentiated].
AB  - Pediatric multiple sclerosis (MS) is one of the most important acquired
      neurological disorders in childhood and adolescence. A timely recognition,
      diagnosis and treatment are of utmost importance. This article highlights the
      current state of knowledge on the etiology, pathogenesis, diagnosis, clinical
      presentation and treatment in childhood. Although the rate of progression of
      disability in the early years is slower in younger patients compared to adults, a
      disease-modifying therapy should be started once MS is diagnosed.

PMID- 29038882
TI  - Etelcalcetide, A Novel Calcimimetic, Prevents Vascular Calcification in A Rat
      Model of Renal Insufficiency with Secondary Hyperparathyroidism.
AB  - Etelcalcetide, a novel peptide agonist of the calcium-sensing receptor, prevents
      vascular calcification in a rat model of renal insufficiency with secondary
      hyperparathyroidism. Vascular calcification occurs frequently in patients with
      chronic kidney disease (CKD) and is a consequence of impaired mineral homeostasis
      and secondary hyperparathyroidism (SHPT). Etelcalcetide substantially lowers
      parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) levels in SHPT
      patients on hemodialysis. This study compared the effects of etelcalcetide and
      paricalcitol on vascular calcification in rats with adenine-induced CKD and SHPT.
      Uremia and SHPT were induced in male Wistar rats fed a diet supplemented with
      0.75% adenine for 4 weeks. Rats were injected with vehicle, etelcalcetide, or
      paricalcitol for 4 weeks from the beginning of adenine diet. Rats fed an adenine
      free diet were included as nonuremic controls. Similar reductions in plasma PTH
      and parathyroid chief cell proliferation were observed in both etelcalcetide- and
      paricalcitol-treated rats. Serum calcium and phosphorus were significantly lower
      in etelcalcetide-treated uremic rats and was unchanged in paricalcitol-treated
      rats. Both serum FGF23 and aortic calcium content were significantly lower in
      etelcalcetide-treated uremic rats compared with either vehicle- or paricalcitol
      treated uremic rats. The degree of aortic calcium content for etelcalcetide
      treated rats was similar to that in nonuremic controls and corroborated findings
      of lack of histologic aortic mineralization in those groups. In conclusion,
      etelcalcetide and paricalcitol similarly attenuated progression of SHPT in an
      adenine rat model of CKD. However, etelcalcetide differentially prevented
      vascular calcification, at least in part, due to reductions in serum FGF23,
      calcium, and phosphorus levels.

PMID- 29038885
TI  - The economic burden of chronic neurological disease.

PMID- 29038886
TI  - Forces generated in stabbing attacks: an evaluation of the utility of the mild,
      moderate and severe scale.
AB  - The commonest way of killing in the UK is by a sharp instrument. Knight reported
      in 1975 that it is impossible to discern with any degree of certainty the degree
      of force used to create a stab wound. Despite this, expert witnesses continue to
      approximate the degree of force used for their reports and evidence in court. It
      is usually subjectively categorized as mild, moderate or severe, based solely on
      the examination of the wound. We undertook a study considering forces generated
      in a range of blunt trauma actions, using a novel force plate dynamometer to
      measure the peak forces obtained by adult male and female volunteers. We then
      studied forces generated by stabbing skin simulants and porcine samples with
      knives and screwdrivers. Men generated more force than women during stabbings
      which was found to be equivalent to somewhere between the blunt trauma actions of
      pushing a button to a single-handed push. When asked to stab using what they
      thought was mild, moderate and severe force, although volunteers were able to
      actively decide the force used, the actual force was found to be influenced by
      the weapon, sex of the individual, hand used and biological/anatomical site
      penetrated. This study shows that the forces generated by volunteers in mild,
      moderate and severe stabbing tests in almost all cases were significantly greater
      than the forces required for skin penetration. We suggest that the use of
      subjective force scales is inappropriate. Rather than use of a subjective scale,
      we suggest that the force required in any stabbing requires investigation in four
      areas: the tip radius of the weapon, minimal force required for penetration, the
      sex of the assailant and whether the force required for penetration is greater
      than that that can be generated by a person stabbing. This allows for the use of
      an evidence-based two-tier scale to suggest the force required.

PMID- 29038887
TI  - Mutations in INF2 may be associated with renal histology other than focal
      segmental glomerulosclerosis.
AB  - BACKGROUND: In 2010, INF2 mutations were associated with autosomal-dominant focal
      segmental glomerulosclerosis (FSGS), clinically presenting with moderate
      proteinuria in adolescence. However, in the meantime, cases with more severe
      clinical courses have been described, including progression to end-stage renal
      disease (ESRD) during childhood. INF2 mutations in patients with isolated FSGS
      are clustered in exons 2 to 4, encoding the diaphanous inhibitory domain,
      involved in the regulation of the podocyte actin cytoskeleton. METHODS: We report
      a family with 14 affected individuals (autosomal-dominant mode of inheritance),
      most of whom presented with nephrotic-range proteinuria, hypertension, and
      progressive renal failure. Four members received a kidney transplant without
      disease recurrence. Two patients underwent renal biopsy with the result of
      minimal-change glomerulopathy and IgA nephropathy respectively. We performed
      mutational analysis of ACTN4, CD2AP, COQ6, INF2, LAMB2, NPHS1, NPHS2, PLCE1,
      TRPC6, and WT1 in the index patient by next-generation sequencing. Additionally,
      in 6 affected and 2 unaffected family members target diagnostics were performed.
      RESULTS: We identified a novel heterozygous mutation c.490G>C (p.(Ala164Pro) in
      exon 3 of the INF2 gene in the index patient and 6 additionally examined affected
      family members. In silico analysis predicted it as "probably damaging".
      Additionally, three patients and 2 unaffected relatives harbored a novel
      heterozygous variant in ACTN4 (c.1149C>G, p.(Ile383Met)) with uncertain
      pathogenicity. CONCLUSION: Mutations in INF2 are associated with familial
      proteinuric diseases - irrespective of the presence of FSGS and in the case of
      rapid disease progression. Therefore, mutational analysis should be considered in
      patients with renal histology other than FSGS and severe renal phenotype.

PMID- 29038889
TI  - Potential factors affecting lung inhomogeneity in acute respiratory distress
      syndrome.

PMID- 29038888
TI  - Simultaneous whole-body 18F-PSMA-1007-PET/MRI with integrated high-resolution
      multiparametric imaging of the prostatic fossa for comprehensive oncological
      staging of patients with prostate cancer: a pilot study.
AB  - INTRODUCTION: The aim of the present study was to explore the clinical
      feasibility and reproducibility of a comprehensive whole-body 18F-PSMA-1007
      PET/MRI protocol for imaging prostate cancer (PC) patients. METHODS: Eight
      patients with high-risk biopsy-proven PC underwent a whole-body PET/MRI (3 h
      p.i.) including a multi-parametric prostate MRI after 18F-PSMA-1007-PET/CT (1 h
      p.i.) which served as reference. Seven patients presented with non-treated PC,
      whereas one patient presented with biochemical recurrence. SUVmean-quantification
      was performed using a 3D-isocontour volume-of-interest. Imaging data was
      consulted for TNM-staging and compared with histopathology. PC was confirmed in
      4/7 patients additionally by histopathology after surgery. PET-artifacts, co
      registration of pelvic PET/MRI and MRI-data were assessed (PI-RADS 2.0). RESULTS:
      The examinations were well accepted by patients and comprised 1 h. SUVmean-values
      between PET/CT (1 h p.i.) and PET/MRI (3 h p.i.) were significantly correlated (p
      < 0.0001, respectively) and similar to literature of 18F-PSMA-1007-PET/CT 1 h vs
      3 h p.i. The dominant intraprostatic lesion could be detected in all seven
      patients in both PET and MRI. T2c, T3a, T3b and T4 features were detected
      complimentarily by PET and MRI in five patients. PET/MRI demonstrated moderate
      photopenic PET-artifacts surrounding liver and kidneys representing high-contrast
      areas, no PET-artifacts were observed for PET/CT. Simultaneous PET-readout during
      prostate MRI achieved optimal co-registration results. CONCLUSIONS: The presented
      18F-PSMA-1007-PET/MRI protocol combines efficient whole-body assessment with high
      resolution co-registered PET/MRI of the prostatic fossa for comprehensive
      oncological staging of patients with PC.

PMID- 29038890
TI  - Massive air embolism in the abdominal aorta.

PMID- 29038892
TI  - [Pityriasis amiantacea and folliculitis decalvans : An unusual manifestation
      associated with antitumor necrosis factor-alpha therapy].
AB  - We report on a 21-year-old woman with a 3-year history of crusts and erosions on
      her scalp that had appeared after starting treatment with adalimumab due to
      Crohn's disease. By clinicopathological correlation pityriasis amiantacea with
      underlying folliculitis decalvans was diagnosed. Topical and systemic antibiotic
      treatment showed rapid response. The occurrence of pityriasis amiantacea in
      folliculitis decalvans associated with tumor necrosis factor (TNF)-alpha
      inhibitor therapy is remarkable and highlights the ambivalent role of TNF-alpha
      in diseases with immunological dysfunctions in combination with infections.

PMID- 29038893
TI  - [Daylight photodynamic therapy : Back to the future?]

PMID- 29038891
TI  - Increase in circulating holotranscobalamin after oral administration of
      cyanocobalamin or hydroxocobalamin in healthy adults with low and normal
      cobalamin status.
AB  - PURPOSE: To investigate the absorption of synthetic cyanocobalamin and natural
      occurring hydroxocobalamin in populations with low and normal cobalamin (vitamin
      B12) status. METHODS: We included adults with low (n = 59) and normal (n = 42)
      cobalamin status and measured the change in serum holotranscobalamin
      (DeltaholoTC) before and after 2 day administration of different doses of
      cyanocobalamin and hydroxocobalamin (CobaSorb test). In the low status group, the
      test was performed using a cross-over design with identical doses of both
      cobalamin forms (1.5, 3, and 6 ug, respectively). In the normal status group, the
      test was performed with either 3, 6, and 9 ug cyanocobalamin (n = 28), or with 9
      ug cyanocobalamin and 9 ug hydroxocobalamin (n = 14). RESULTS: In both groups,
      median DeltaholoTC (pmol/L) was higher after intake of cyanocobalamin compared to
      (hydroxocobalamin) [low status: 1.5 ug: 19 (6); 3 ug: 23 (7); 6 ug: 30 (14);
      normal status: 9 ug: 30 (13) pmol/L]. Independent of B12 form, no difference was
      observed in DeltaholoTC between those receiving 1.5 and 3 ug in the low status
      group or 6 and 9 ug cyanocobalamin in the normal status group. However, in both
      groups, administration of 6 ug cobalamin resulted in a significant higher
      DeltaholoTC than did 3 ug [low status: p = 0.02 (0.009) for cyanocobalamin
      (hydroxocobalamin); normal status: p = 0.03 for cyanocobalamin]. CONCLUSIONS:
      Administration of cyanocobalamin resulted in a more than twofold increase in
      holoTC in comparison with hydroxocobalamin. The absorptive capacity was reached
      only by doses above 3 ug cobalamin. Our results underscore the importance of
      using the same form of cobalamin when comparing uptake under different
      conditions. CLINICAL TRIAL REGISTRY NUMBER: NCT02832726 at
      https://clinicaltrials.gov and 2016/09/012147 at Clinical Trials Registry India.

PMID- 29038894
TI  - The supraorbital eyebrow approach for removal of craniopharyngioma in children: a
      case series.
AB  - OBJECTIVE: Craniopharyngiomas can be a surgical challenge for the pediatric
      neurosurgeon. Ideally, total removal must be achieved. However, the need to
      reduce surgical morbidity and preserve quality of life has led to a number of
      neurosurgical approaches in order to attain this goal. The aim of this article is
      to present an alternative surgical approach to these lesions and to provide the
      rationale for this technique. MATERIAL AND METHODS: Medical charts and operative
      records of eight pediatric patients harboring craniopharyngiomas who underwent
      surgical treatment using a supraorbital eyebrow approach (SOA) were reviewed from
      2014 to 2016. Only patients younger than 18 years with a minimum follow-up of 12
      months were included in this study. Using pre-operative magnetic resonance (MRI)
      scans, tumors were classified according to their degree of hypothalamic
      involvement. The surgical technique is also described in detail. RESULTS: The
      study group included six males and two females with a mean age of 10 years
      (range, 2-16 years). The SOA was used successfully in elective surgery of eight
      craniopharyngiomas. The hypothalamus was displaced by the tumor in three patients
      and severely involved in five patients. Subtotal resection was undertaken in six
      patients, whereas gross-total resection was achieved in two. Endoscopic
      assistance was used after standard microscopic visualization in two out of eight
      cases. Cosmetic outcomes were excellent, and the complication rate related to the
      surgical procedure was quite low, apart from diabetes insipidus (which occurred
      in three out of the eight patients). In one patient, a large subdural collection
      needed surgery for evacuation. Mean follow-up was 23.2 months (range, 12-36
      months). Additionally, no CSF leak or wound infection was identified.
      CONCLUSIONS: The supraorbital eyebrow approach is an alternative route to operate
      on craniopharyngiomas in properly selected cases of all pediatric age ranges,
      from infants to teenagers. There is sufficient working space for the endoscope
      and all instruments, allowing for endoscopic assistance and bimanual surgical
      technique. Cosmetic results are excellent, and complications related to the
      approach are minimal.

PMID- 29038895
TI  - The network remains.
AB  - Eric Davidson was a legend both in his science and his personality. He inspired
      and challenged a new generation of developmental biologists and I was lucky to be
      one of them. He changed the way we think about biological interactions by
      synthesizing a large scale, almost incomprehensible set of data into a causal
      model of a gene regulatory network. While his death leaves a big hole in our
      lives, his contribution to the conceptualization of regulatory biology will
      inspire developmental and evolutionary biologists for decades to come.

PMID- 29038896
TI  - Inducible ATF3-NFAT axis aggravates podocyte injury.
AB  - : Podocyte injury and loss contribute to proteinuria, glomerulosclerosis, and
      eventually kidney failure. Activating transcription factor 3 (ATF3) is a stress
      inducible transcription factor that is transiently expressed following
      stimulation. However, we show for the first time an induction of ATF3 in
      podocytes from patients with chronic kidney disease, including minimal change
      disease, focal segmental glomerulosclerosis, and diabetic nephropathy. The role
      of ATF3 induction in podocytes under chronic conditions is currently unknown.
      Compared with the control (C57 or BKS), ATF3 expression was elevated in animal
      model of proteinuria (LPS-treated C57 mice) and the model of diabetic nephropathy
      (db/db mice). Similarly, ATF3 was increased in high glucose (HG)-treated,
      lipopolysaccharide (LPS)-treated, or Ionomycin-treated podocytes in vitro.
      Overexpression of ATF3 increased podocyte apoptosis and decreased expression of
      podocin, the cell marker of podocyte; in contrast, ATF3-small interfering RNA
      knockdown reduced podocyte apoptosis and increased podocin expression. The
      translocation of ATF3 to the nucleus was increased upon stimulation. ATF3
      directly modulates the regulation of NFATc1 gene promoter activity and alters the
      expression of Wnt6 and Fzd9, direct target genes of NFATc1 signaling. The ATF3
      binding site of NFATc1 gene promoter is located at the region 671-775 base pairs
      upstream of the transcription start site. These results indicate a novel
      inducible axis of ATF3-NFAT in podocyte injury and loss. KEY MESSAGES: * The
      stress factor ATF3 is induced in podocytes from proteinuric patients, including
      diabetes. * ATF3 increased podocyte apoptosis and injury. * ATF3 directly
      modulates the regulation of NFATc1 gene promoter activity.

PMID- 29038897
TI  - [Acute achilles tendon rupture : State of the art].
AB  - The most favorable treatment for acute Achilles tendon ruptures remains
      controversial. In particular, three key questions are intensively debated: is
      operative or non-operative treatment superior? If surgery is performed, should
      open or minimally invasive percutaneous techniques be used? How should the follow
      up treatment be carried out? The aim of this article is to answer these essential
      questions based on the currently available evidence. Non-operative treatment
      leads to a higher rate of re-ruptures and inferior functional results when
      compared to operative treatment. The major disadvantage of open surgery is the
      increased risk of wound healing problems and wound infections. Due to the
      development of minimally invasive percutaneous techniques, complication rates
      could be significantly reduced and patient satisfaction could be significantly
      improved, without increasing the risk of re-ruptures. The functional outcome is
      still partially unsatisfactory independent of the type of treatment. This is
      particularly expressed in weakness of the gastrocnemius-soleus muscle complex;
      therefore, the follow-up treatment is of fundamental importance. The available
      evidence clearly underlines the importance of early weight bearing and
      mobilization of the ankle joint, as it is safe and leads to better function,
      patient satisfaction and faster return to work or sport, compared with partial
      weight bearing and immobilization. Nevertheless, treatment protocols vary greatly
      with the majority still carrying out open suture and immobilizing follow-up
      treatment with fixed plantar flexion. Based on the available data the authors
      recommend minimally invasive percutaneous suture of the tendon followed by
      progressive functional rehabilitation. Implementation of the available evidence
      into routine practice is the next important step for successful treatment of this
      challenging injury.

PMID- 29038898
TI  - Molecular and immunological characterisation of tropomyosin from Anisakis
      pegreffii.
AB  - Tropomyosin (TM) is a major allergen in shellfish, known to cross-react with
      mite, cockroach and/or some roundworm (nematode) TM. In this study, we aimed to
      express and purify TM from the parasitic nematode Anisakis pegreffii and also to
      characterise its cross-reactivity with TM from shellfish. A. pegreffii was
      isolated from the flathead tiger fish (Neoplatycephalus richardsoni) and
      characterised using single-strand conformation polymorphism (SSCP)-based
      sequencing of the first and second internal transcribed spacers (ITS-1 and ITS-2)
      of nuclear ribosomal DNA. The recombinant tropomyosin (rTM) of A. pegreffii was
      expressed, purified and confirmed by immunohistochemistry, sequencing and LC
      MS/MS analyses. Immunohistochemistry showed the muscle and the base layer of the
      third-stage larvae (L3) of A. pegreffii as the location of TM in A. pegreffii.
      The molecular relationship of TM of A. pegreffii with homologs from other
      nematodes and crustaceans was inferred from phylogenetic analysis. Immunogenicity
      of TM from A. pegreffii was tested by immunoblotting, which showed that rTM from
      A. pegreffii binds to IgE from sera of patients with allergy to crustaceans.
      Immunoblotting also showed that the anti-TM monoclonal antibody (MAb) did not
      recognise rTM from A. pegreffii. The rTM from A. pegreffii was, however,
      recognised by anti-TM polyclonal antibodies (PAbs) as well as anti-crustacean
      polyclonal antibodies (PAbs). The detection of specific serum IgE antibody
      against parasite TM has been proposed as a useful approach for the diagnosis of
      parasite-induced allergy. The findings of this study merit further exploration of
      the cross-reactive allergenic proteins of Anisakis for improved, future diagnosis
      of allergenic diseases.

PMID- 29038900
TI  - Correction to: Dietary Interventions and Multiple Sclerosis.
AB  - The original version of this article contains an error in the second sentence of
      the second paragraph of the Paleolithic Diet section.

PMID- 29038899
TI  - The Use of Primary Prevention Statin Therapy in Those Predisposed to
      Atherosclerosis.
AB  - PURPOSE OF REVIEW: Many guidelines exist for the use of statins in the primary
      prevention of atherosclerotic cardiovascular disease (ASCVD). Few have focused on
      disease specific states that predispose to ASCVD. This review is intended to
      focus on the recommendations and evidence in inflammatory diseases that
      predispose to an increased risk of ASCVD beyond what conventional cardiac risk
      scores would predict. RECENT FINDINGS: Certain autoimmune inflammatory diseases
      such as rheumatoid arthritis (RA), systemic lupus erythematous (SLE), and
      psoriasis/psoriatic arthritis have all been shown to increase the risk of ASCVD.
      Other diseases such as human immunodeficiency virus (HIV) and mediastinal
      radiation have also been correlated with increased ASCVD. In RA and HIV, the
      evidence suggests a benefit to added statin therapy and society guidelines favor
      early initiation. The evidence for statin therapy in RA is limited to
      observational studies with small secondary analysis. In HIV, there is a large
      ongoing clinical trial to assess efficacy. In those with psoriasis and psoriatic
      arthritis, there is limited evidence for or against statin therapy independent of
      a calculated cardiac risk score. Finally, in SLE and in those with exposure to
      mediastinal radiation, cardiac events remain high, but evidence is limited on the
      beneficial effects of statin therapy. There are many individuals who have an
      increased risk for ASCVD above what is predicted from a cardiac risk score. It
      would be beneficial to create risk prediction models with statin therapy
      recommendations that are tailored to those predisposed to accelerated
      atherosclerosis.

PMID- 29038901
TI  - Pre-peritoneal local anaesthetic does not reduce post-operative pain in
      laparoscopic total extra-peritoneal inguinal hernia repair: double-blinded
      randomized controlled trial.
AB  - PURPOSE: Laparoscopic total extra-peritoneal hernia repair (TEP) is associated
      with less post-operative pain and earlier return to normal activity compared to
      open hernia repair (OHP). Despite this, post-operative pain remains a major
      issue. The aim of this double-blinded randomized controlled trial was to identify
      whether the instillation of local anaesthetic in the pre-peritoneal space
      improves pain scores following TEP. METHODS: One hundred patients undergoing
      laparoscopic total pre-peritoneal hernia repair (TEP) between the years of 2009
      2014 were included. Patients were randomly assigned to receive either 20 mL of
      normal saline or 0.25% bupivacaine with adrenaline. Visual analogue scores (VAS 0
      10) were recorded post-operatively at the 4 h, 1 day, 2 weeks, and 6 week mark.
      Secondary endpoints included complications, time to discharge, and return to
      normal activity. RESULTS: 51 patients were allocated to the local group. 49
      patients were allocated to the placebo group. The baseline characteristics and
      demographics of patients in both groups were comparable. Patients in the local
      group had similar VAS scores compared to the placebo group at both 4 h (1.1 vs.
      1.4, respectively; p = 0.19) and 24 h (2.1 vs. 2.3; p = 0.63). No statistically
      significant difference noted in other primary and secondary outcomes. CONCLUSION:
      Although the concept of pre-peritoneal local anaesthetic instillation following
      laparoscopic TEP is attractive, this appropriately powered study has failed to
      show any advantage in pain scores at 4 and 24 h. The pain scores recorded,
      however, were remarkably low in both groups.

PMID- 29038902
TI  - [Urinary tract infections : What has been confirmed in therapy?]
AB  - Urinary tract infections (UTIs) affect approximately 150 million people worldwide
      per year, causing annual health costs of over three billion dollars just in the
      USA. Every second woman experiences at least one UTI in her lifetime, with every
      one in four experiencing recurrence. Uncomplicated infections like single or
      recurrent cystitis and pyelonephritis can be distinguished from complicated
      disease. UTIs in men can spread to the male glands, causing prostatitis and
      epididymitis. Antibiotic therapy is the standard procedure for UTIs. However, the
      extensive and sometimes irrational use of antibiotics for the treatment of
      infections has led to an increase in the incidence of multiresistant pathogens in
      recent years. Therefore, preventive nonantibiotic approaches are of great
      interest. This article provides an overview of the current management of
      urological infections as well as an outline of nonantibiotic preventive treatment
      modalities.

PMID- 29038903
TI  - [Nontuberculous mycobacteria in sputum : Recommendations for diagnosis and
      treatment].
AB  - Pulmonary diseases caused by nontuberculous mycobacteria (NTM) have increased
      over the last years and decades in Germany and also worldwide. Because the
      disease is more frequent in patients with immunodeficiencies and chronic
      respiratory diseases, e.g. bronchiectasis, advanced chronic obstructive lung
      disease (COPD) and cystic fibrosis (CF), an infection with mycobacteria should
      always be considered in this patient group. The detection in sputum alone is not
      an indication for treatment but the correct diagnosis should be based on the
      appropriate clinical symptoms as well as radiological and microbiological
      criteria. The diagnosis is often delayed because the symptoms are unspecific. The
      treatment of pulmonary NTM disease is difficult and tedious and for these reasons
      is often prematurely terminated. Adherence of treating physicians to the
      guidelines is also conspicuously low. Before starting treatment, it is important
      to carefully define the goals and clarify the risks and benefits of the treatment
      with the patient. As adverse toxic events can occur during treatment, it should
      be closely monitored. In the case of an infrequent pathogen or a severe course of
      the disease, referral to an NTM specialist center should be undertaken.

PMID- 29038904
TI  - The ability of emergency physicians to diagnose and score acute pancreatitis on
      computed tomography: authors' response.

PMID- 29038905
TI  - Recent advances in production of 5-aminolevulinic acid using biological
      strategies.
AB  - 5-Aminolevulinic acid (5-ALA) is the precursor for the biosynthesis of
      tetrapyrrole compounds and has broad applications in the medical and agricultural
      fields. Because of the disadvantages of chemical synthesis methods, microbial
      production of 5-ALA has drawn intensive attention and has been regarded as an
      alternative in the last years, especially with the rapid development of metabolic
      engineering and synthetic biology. In this mini-review, recent advances on the
      application and microbial production of 5-ALA using novel biological approaches
      (such as whole-cell enzymatic-transformation, metabolic pathway engineering and
      cell-free process) are described and discussed in detail. In addition, the
      challenges and prospects of synthetic biology are discussed.

PMID- 29038908
TI  - Eric Davidson, his philosophy, and the history of science.
AB  - Eric Davidson, a passionate molecular developmental biologist and intellectual,
      believed that conceptual advances in the sciences should be based on knowledge of
      conceptual history. Convinced of the superiority of a causal-analytical approach
      over other methods, he succeeded in successfully applying this approach to the
      complex feature of organismal development by introducing the far-reaching concept
      of developmental Gene Regulatory Networks. This essay reviews Davidson's
      philosophy, his support for the history of science, and some aspects of his
      scientific personality.

PMID- 29038907
TI  - Muscular vasculitis confined to lower limbs: description of two case reports and
      a review of the literature.
AB  - Muscular involvement is common during systemic vasculitides, such as
      polyarteritis nodosa. However, in rare cases, muscular involvement can be the
      only clinically evident feature of the disease. The clinical pattern of isolated
      muscular vasculitis may mimic several other inflammatory muscle disorders, such
      as idiopathic inflammatory myositis, and may represent a challenge in
      differential diagnosis. Herewith, we present two clinical cases as examples of
      peculiar clinical and histopathological characteristics of isolated muscular
      vasculitis. Our patients were successfully treated with steroids and
      immunosuppressive agents. Moreover, we provide a review of the recent existing
      medical literature. Our cases suggest the importance of performing muscle biopsy
      in patients with muscular symptoms to guide the diagnosis and the treatment.

PMID- 29038906
TI  - PCSK9 Mutations in Familial Hypercholesterolemia: from a Groundbreaking Discovery
      to Anti-PCSK9 Therapies.
AB  - PURPOSE OF REVIEW: In 2003, Abifadel et al. (Nat. Genet. 34:154-156, 2003)
      identified PCSK9, encoding proprotein convertase subtilisin/kexin type 9, as the
      third causal gene for autosomal dominant hypercholesterolemia. This review
      focuses on the main steps from this major breakthrough in familial
      hypercholesterolemia (FH) to the latest clinical trials with the anti-PCSK9
      antibodies. RECENT FINDINGS: The year 2015 was remarkable in cardiovascular
      disease through the field of cholesterol. Nearly 30 years after the discovery of
      statins, a new class of effective lipid-lowering drugs has emerged: the anti
      PCSK9 antibodies. The discovery of the first gain-of-function mutations of PCSK9
      in FH rapidly became the center of interest of researchers worldwide. Preclinical
      and clinical studies launched by pharmaceutical companies led to the first three
      anti-PCSK9 antibodies, two of which (evolocumab and alirocumab) reduce LDL
      cholesterol levels by 50-60% and received FDA and European Medicines Agency
      approvals in 2015 on top of statin therapy. Recently, results of the Further
      Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated
      Risk (FOURIER) trial, the outcome trial of evolocumab over 2.2 years, showed a
      reduction of 15-20% in the risk of major cardiovascular outcomes in high-risk
      patients receiving statin therapy. Results of ODYSSEY OUTCOMES trial, evaluating
      the effect of alirocumab in 18,000 patients with established CVD are also eagerly
      awaited in 2018. The evolution of research on PCSK9, starting from the discovery
      of the first set of mutations in PCSK9 in FH in 2003, is an amazing example of
      successful translational research. It shows how rigorous and powered genetic
      analyses can lead to the discovery of a new class of lipid-lowering drugs that
      give hope in fighting high cholesterol levels and their cardiovascular
      complications.

PMID- 29038909
TI  - Citrus plants exude proline and phytohormones under abiotic stress conditions.
AB  - KEY MESSAGE: This article describes the root exudation of proline and
      phytohormones in citrus and their involvement in salt- and heat-stress responses.
      Plants are constantly releasing several compounds to the rhizosphere through
      their roots, including primary and secondary metabolites. Root exudation can be
      affected by growth conditions, including pH, nutrient availability, soil
      salinity, or temperature. In vitro-cultured plants of two citrus genotypes with
      contrasting tolerance to salt- and heat-stress conditions were used as plant
      material. Proline and phytohormone contents in root exudates from plants
      subjected to salt or high-temperature conditions were evaluated. In addition,
      tissue damage and lipid peroxidation together with endogenous levels of chloride,
      proline, and phytohormones were determined in roots and shoots. Proline was
      released in larger quantities to the rhizosphere when plants were subjected to
      salt or heat stress. In each stress condition, the concentration of this amino
      acid was higher in the exudates obtained from plants tolerant to this particular
      stress condition. On the other hand, root exudation of phytohormones salicylic
      acid, indole acetic acid, abscisic acid, and jasmonic acid generally increased
      under both adverse conditions. Results confirm a phytohormone exudation in citrus
      plants, which had not been described previously and can have an important role in
      the rhizosphere communication. Moreover, stress conditions and the different
      tolerance of each genotype to the particular stress significantly modify the
      exudation pattern both quantitatively and qualitatively.

PMID- 29038910
TI  - Analysis of somaclonal variation in transgenic and regenerated plants of
      Arabidopsis thaliana using methylation related metAFLP and TMD markers.
AB  - KEY MESSAGE: We provide evidence that nucleotide sequence and methylation status
      changes occur in the Arabidopsis genome during in vitro tissue culture at a
      frequency high enough to represent an important source of variation. Somaclonal
      variation is a general consequence of the tissue culture process that has to be
      analyzed specifically when regenerated plants are obtained in any plant species.
      Currently, there are few studies about the variability comprising sequence
      changes and methylation status at the DNA level, generated by the culture of A.
      thaliana cells and tissues. In this work, two types of highly reproducible
      molecular markers, modified methylation sensitive AFLP (metAFLP) and transposon
      methylation display (TMD) have been used for the first time in this species to
      analyze the nucleotide and cytosine methylation changes induced by transformation
      and tissue culture protocols. We found significantly higher average methylation
      values (7.5%) in regenerated and transgenic plants when compared to values
      obtained from seed derived plants (3.2%) and that the main component of the
      somaclonal variation present in Arabidopsis clonal plants is genetic rather than
      epigenetic. However, we have found that the Arabidopsis regenerated and
      transgenic plants had a higher number of non-fully methylated sites flanking
      transposable elements than the control plants, and therefore, their mobilization
      can be facilitated. These data provide further evidence that changes in
      nucleotide sequence and methylation status occur in the Arabidopsis genome during
      in vitro tissue culture frequently enough to be an important source of variation
      in this species.

PMID- 29038911
TI  - Negative regulation of daptomycin production by DepR2, an ArsR-family
      transcriptional factor.
AB  - Daptomycin, a lipopeptide antibiotic potently active against Gram-positive
      bacterial pathogens, is produced by Streptomyces roseosporus, but the
      transcriptional regulation on its biosynthesis is not fully understood. Here, we
      report that DepR2, an ArsR-family transcriptional regulator isolated previously
      by DNA-affinity purification, interacts directly with dptEp, the major promoter
      of the daptomycin gene cluster. DepR2 binds to an imperfect palindromic sequence
      at the very upstream of dptEp. Meanwhile, higher dptEp activities were
      consistently observed in the DeltadepR2 mutant, correlating with a nearly 2.5
      fold increased production of daptomycin and three structurally related secondary
      metabolites A21978C1-3. Thus, our data suggest that the ArsR-family
      transcriptional regulator DepR2 negatively regulates production of daptomycin by
      directly repressing the expression of its gene cluster in S. roseosporus. To the
      best of our knowledge, this is the first report to show the involvement of an
      ArsR-family regulator in the direct regulation of secondary metabolite
      biosynthesis in Streptomyces.

PMID- 29038912
TI  - [Erratum to: The 2016 update of the S3 guideline for malignant tumours of the
      ovary : Role of pathology in diagnosis, therapy and clinical management of
      epithelial tumours].

PMID- 29038914
TI  - Homage to Eric Davidson.
AB  - The Britten-Davidson model of genetic regulation was well received by American
      molecular biologists and embryologists, but not by the members of the French
      School of molecular biology. In particular, Francois Jacob considered it too
      abstract and too removed from experiments. I re-examine the contrast between the
      Britten-Davidson model and the operon model by Jacob and Monod, the different
      scientific contexts in which they were produced and the different roles they
      played. I also describe my recent encounters with Eric Davidson, and how I
      discovered the extraordinary continuity of his work on the development of the sea
      urchin, as well as his rich personality.

PMID- 29038913
TI  - [Ocular melanomas : An update].
AB  - Melanoma is the most common type of primary cancer to affect the adult eye.
      Approximately 95% of ocular melanomas are intraocular and arise from the uvea (i.
      e. iris, ciliary body, and choroid), while the remaining 5% are located in the
      conjunctiva. Although both uveal and conjunctival melanomas are thought to derive
      from malignantly transformed melanocytes, uveal melanoma is clinically and
      biologically distinct from conjunctival melanoma, and indeed from its more common
      cutaneous counterpart. Intense efforts have been recently made to understand the
      molecular biology involved in the development of ocular melanomas, and in their
      progression. Molecular advances, particularly for uveal melanoma, have enhanced
      prognostication and the identification of rational therapeutic targets for
      disseminated disease. In this review, recent advances in the molecular
      characterisation of both uveal and conjunctival melanomas are discussed, and how
      these may be used to develop personalised therapeutic strategies.

PMID- 29038915
TI  - Glycation of Lys-16 and Arg-5 in amyloid-beta and the presence of Cu2+ play a
      major role in the oxidative stress mechanism of Alzheimer's disease.
AB  - Extensive research has linked the amyloid-beta (Abeta) peptide to neurological
      dysfunction in Alzheimer's disease (AD). Insoluble Abeta plaques in the AD
      patient brain contain high concentrations of advanced glycation end-products
      (AGEs) as well as transition metal ions. This research elucidated the roles of
      Abeta, sugars, and Cu2+ in the oxidative stress mechanism of AD at the molecular
      level. Mass spectral (MS) analysis of the reactions of Abeta with two
      representative sugars, ribose-5-phosphate (R5P) and methylglyoxal (MG), revealed
      Lys-16 and Arg-5 as the primary glycation sites. Quantitative analysis of
      superoxide [Formula: see text] production by a cyt c assay showed that Lys-16
      generated four times as much [Formula: see text] as Arg-5. Lys-16 and Arg-5 in
      Abeta1-40 are both adjacent to histidine residues, which are suggested to
      catalyze glycation. Additionally, Lys-16 is close to the central hydrophobic core
      (Leu-17-Ala-21) and to His-13, both of which are known to lower the pKa of the
      residue, leading to increased deprotonation of the amine and an enhanced
      glycation reactivity compared to Arg-5. Gel electrophoresis results indicated
      that all three components of AD plaques-Abeta1-40, sugars, and Cu2+-are necessary
      for DNA damage. It is concluded that the glycation of Abeta1-40 with sugars
      generates significant amounts of [Formula: see text], owing to the rapid
      glycation of Lys-16 and Arg-5. In the presence of Cu2+, [Formula: see text]
      converts to hydroxyl radical (HO.), the source of oxidative stress in AD.

PMID- 29038918
TI  - Mechanisms and causality in molecular diseases.
AB  - How is a disease contracted, and how does it progress through the body? Answers
      to these questions are fundamental to understanding both basic biology and
      medicine. Advances in the biomedical sciences continue to provide more tools to
      address these fundamental questions and to uncover questions that have not been
      thought of before. Despite these major advances, we are still facing conceptual
      and technical challenges when learning about the etiology of disease, especially
      for genetic diseases. In this review, we illustrate this point by discussing the
      causal links between molecular mechanisms and systems-level phenotypes in
      molecular diseases. We begin with an examination of sickle cell anemia, and how
      mechanisms of the disease have been comprehended over the last century. While
      sickle cell anemia involves a mutation in a single protein in a single cell type,
      other diseases involve mutations in networks with many protein interactions and
      in diverse cell types. We introduce the challenges that result from these
      differences and illustrate the current obstacles by discussing the RASopathies, a
      recently discovered class of developmental syndromes that result from mutations
      in signaling networks. Methods to study mutant genotypes that lead to mutant
      phenotypes are discussed, particularly the use of model organisms and mutant
      proteins to study protein interactions that may be important for development of
      disease. These studies will point toward the future of diagnosing and treating
      genetic disease.

PMID- 29038916
TI  - Functional characterization of chloroplast-targeted RbgA GTPase in higher plants.
AB  - KEY MESSAGE: Plant RbgA GTPase is targeted to chloroplasts and co-fractionated
      with chloroplast ribosomes, and plays a role in chloroplast rRNA processing
      and/or ribosome biogenesis. Ribosome Biogenesis GTPase A (RbgA) homologs are
      evolutionarily conserved GTPases that are widely distributed in both prokaryotes
      and eukaryotes. In this study, we investigated functions of chloroplast-targeted
      RbgA. Nicotiana benthamiana RbgA (NbRbgA) and Arabidopsis thaliana RbgA (AtRbgA)
      contained a conserved GTP-binding domain and a plant-specific C-terminal domain.
      NbRbgA and AtRbgA were mainly localized in chloroplasts, and possessed GTPase
      activity. Since Arabidopsis rbgA null mutants exhibited an embryonic lethal
      phenotype, virus-induced gene silencing (VIGS) of NbRbgA was performed in N.
      benthamiana. NbRbgA VIGS resulted in a leaf-yellowing phenotype caused by
      disrupted chloroplast development. NbRbgA was mainly co-fractionated with 50S/70S
      ribosomes and interacted with the chloroplast ribosomal proteins cpRPL6 and
      cpRPL35. NbRbgA deficiency lowered the levels of mature 23S and 16S rRNAs in
      chloroplasts and caused processing defects. Sucrose density gradient
      sedimentation revealed that NbRbgA-deficient chloroplasts contained reduced
      levels of mature 23S and 16S rRNAs and diverse plastid-encoded mRNAs in the
      polysomal fractions, suggesting decreased protein translation activity in the
      chloroplasts. Interestingly, NbRbgA protein was highly unstable under high light
      stress, suggesting its possible involvement in the control of chloroplast
      ribosome biogenesis under environmental stresses. Collectively, these results
      suggest a role for RbgA GTPase in chloroplast rRNA processing/ribosome
      biogenesis, affecting chloroplast protein translation in higher plants.

PMID- 29038917
TI  - Chromatin-associated regulation of sorbitol synthesis in flower buds of peach.
AB  - KEY MESSAGE: PpeS6PDH gene is postulated to mediate sorbitol synthesis in flower
      buds of peach concomitantly with specific chromatin modifications. Perennial
      plants have evolved an adaptive mechanism involving protection of meristems
      within specialized structures named buds in order to survive low temperatures and
      water deprivation during winter. A seasonal period of dormancy further improves
      tolerance of buds to environmental stresses through specific mechanisms poorly
      known at the molecular level. We have shown that peach PpeS6PDH gene is down
      regulated in flower buds after dormancy release, concomitantly with changes in
      the methylation level at specific lysine residues of histone H3 (H3K27 and H3K4)
      in the chromatin around the translation start site of the gene. PpeS6PDH encodes
      a NADPH-dependent sorbitol-6-phosphate dehydrogenase, the key enzyme for
      biosynthesis of sorbitol. Consistently, sorbitol accumulates in dormant buds
      showing higher PpeS6PDH expression. Moreover, PpeS6PDH gene expression is
      affected by cold and water deficit stress. Particularly, its expression is up
      regulated by low temperature in buds and leaves, whereas desiccation treatment
      induces PpeS6PDH in buds and represses the gene in leaves. These data reveal the
      concurrent participation of chromatin modification mechanisms, transcriptional
      regulation of PpeS6PDH and sorbitol accumulation in flower buds of peach. In
      addition to its role as a major translocatable photosynthate in Rosaceae species,
      sorbitol is a widespread compatible solute and cryoprotectant, which suggests its
      participation in tolerance to environmental stresses in flower buds of peach.

PMID- 29038919
TI  - Initial orthostatic and non-orthostatic hypotension in wrestler's syncope.

PMID- 29038920
TI  - Stener-like lesion of the lateral collateral ligament of the first
      metatarsophalangeal joint.
AB  - Displaced ulnar collateral ligament injuries of the metacarpophalangeal joint of
      the thumb, also known as Stener lesions, are a well-recognized clinical entity,
      requiring surgical intervention because of the trapped location of the torn
      lateral collateral ligament superficial to the adductor aponeurosis of the thumb.
      We report a similar lesion located at the first metatarsophalangeal joint, to our
      knowledge the first ever described in the literature. In our patient, magnetic
      resonance imaging showed a full-thickness tear of the lateral collateral ligament
      of the first metatarsophalangeal joint, as well as a full-thickness tear of the
      extensor hood, with dislocation of the proximal part of the ruptured lateral
      collateral ligament to a position superficial to the extensor hood. Analogous to
      true Stener lesions, we are convinced these patients also need early surgical
      repair. Therefore, we would like to raise awareness about their existence to
      ensure adequate management of these lesions, in order to prevent possible long
      term complications like chronic pain, instability, and joint degeneration.

PMID- 29038921
TI  - Muscular sarcoidosis involving the chest and abdominal walls: case report with MR
      imaging.
AB  - Sarcoidosis is an inflammatory disorder that is characterized by the presence of
      noncaseating granulomas in tissues, involving many organs and tissues. Extra
      pulmonary, especially muscular sarcoidosis is a rare condition. The most common
      location of the muscular sarcoidosis is known to be the proximal muscles of the
      extremities; however, there have been no cases of diffuse involvement of the
      chest and abdominal wall muscles. Here, we report a rare muscular sarcoidosis
      with infiltrative pattern in the chest and abdominal wall muscles and describe
      the MR imaging findings that were mistaken as lymphoma at initial diagnosis.
      Although our case did not show characteristic MR findings of muscular
      sarcoidosis, clinicians or radiologists who are aware of these imaging features
      can perform early systemic survey for sarcoidosis. Also muscle biopsy is very
      important to confirm the sarcoidosis and distinguish it from other tumors.

PMID- 29038923
TI  - Improvement of uridine production in Bacillus subtilis by metabolic engineering.
AB  - OBJECTIVES: To construct a Bacillus subtilis strain for improved uridine
      production. RESULTS: The AAG2846-2848 fragment of the pyrAB gene, encoding
      carbamoylphosphate synthetase, was deleted in B. subtilis TD246 leading to a 245%
      increase of uridine production and the conversion from glucose to uridine
      increased by 10.5%. Overexpression of the pyr operon increased the production of
      uridine by a further 31% and the conversion rate of glucose to uridine was
      increased by 18%. In addition, the blocking of arginine synthesis or disabling of
      glutamate dehydrogenase significantly enhanced the uridine production. The
      highest-producing strain, B. subtilis TD297, accumulated 11 g uridine/l with a
      yield of 240 mg uridine/g glucose in shake-flask cultivation. CONCLUSION: This is
      the first report of engineered B. subtilis strains which can produce more than 11
      g uridine/l, with a yield reaching 240 mg uridine/g glucose in shake-flask
      cultivation.

PMID- 29038922
TI  - Lower Fractional Anisotropy in the Gray Matter of Amygdala-Hippocampus-Nucleus
      Accumbens Circuit in Methamphetamine Users: an In Vivo Diffusion Tensor Imaging
      Study.
AB  - The basolateral amygdala (BLA), hippocampal ventral subiculum, and nucleus
      accumbens (NAc) comprise the amygdala-hippocampus-NAc (AHN) circuit, which is
      implicated in drug seeking and reward. The goal of this study was to evaluate
      microstructural changes and relevant clinical features of the AHN circuit gray
      matter (GM) in methamphetamine (MA) users using diffusion tensor imaging (DTI).
      Thirty MA users and 30 age-matched normal volunteers underwent 3-T MR imaging to
      obtain structural T1-weighted images and DTI data. Freesurfer software was used
      to automatically segment the NAc and subiculum. A Julich probability map was
      employed to parcellate the BLA. Fractional anisotropy (FA) and mean diffusivity
      (MD) maps were generated and non-linearly coregistered to structural space. DTI
      measures of the AHN circuit GM were compared between MA users and controls using
      repeated measures analysis of variance. Correlation analyses were performed
      between DTI measures and clinical characteristics. Anatomical correlations
      between the NAc and BLA/subiculum in both groups were assessed using correlation
      analyses. The MA group had significant lower FA in the bilateral BLA, subiculum,
      and NAc. Higher total MA dose corresponded with lower FA in all three structures.
      Hamilton Anxiety Rating Scale scores negatively correlated with the right
      subiculum FA. Lower left BLA FA was associated with higher thinking disorder and
      hostile-suspicion factor scores. Left BLA FA was significantly associated with
      bilateral NAc FA in MA users. Those findings provided neuroimaging evidence of MA
      induced microstructural impairment in the AHN circuit GM. Enhanced anatomical
      correlations between the left BLA and bilateral NAc may be part of the mechanism
      of MA intake relapse and for development of psychosis.

PMID- 29038924
TI  - Inactivation of virginiamycin by Aureobasidium pullulans.
AB  - OBJECTIVE: To test the inactivation of the antibiotic, virginiamycin, by laccase
      induced culture supernatants of Aureobasidium pullulans. RESULTS: Fourteen
      strains of A. pullulans from phylogenetic clade 7 were tested for laccase
      production. Three laccase-producing strains from this group and three previously
      identified strains from clade 5 were compared for inactivation of virginiamycin.
      Laccase-induced culture supernatants from clade 7 strains were more effective at
      inactivation of virginiamycin, particularly at 50  degrees C. Clade 7 strain NRRL
      Y-2567 inactivated 6 ug virginiamycin/ml within 24 h. HPLC analyses indicated
      that virginiamycin was degraded by A. pullulans. CONCLUSIONS: A. pullulans has
      the potential for the bioremediation of virginiamycin-contaminated materials,
      such as distiller's dry grains with solubles (DDGS) animal feed produced from
      corn-based fuel ethanol production.

PMID- 29038925
TI  - miR-1260b promotes cell migration and invasion of hepatocellular carcinoma by
      targeting the regulator of G-protein signaling 22.
AB  - OBJECTIVES: To investigate whether miR-1260b can regulate migration and invasion
      of hepatocellular carcinoma (HCC) by targeting RGS22. RESULTS: miR-1260b was up
      regulated in HCC tissues compared with their corresponding non-cancerous tissues.
      Over-expression of miR-1260b increased migration and invasion of HepG2 and SMMC
      7721 cells associated with HCC. Regulator of G-protein signaling 22 (RGS22) was
      identified as a directly target of miR-1260b and was inhibited by miR-1260b.
      Knockdown of RGS22 increased proliferation of HCC cells. CONCLUSIONS: The new
      identified miR-1260b/RGS22 axis provides useful therapeutic methods for treatment
      of HCC deepening on our understanding of underlying mechanisms of HCC
      tumorigenesis.

PMID- 29038926
TI  - Deactivation kinetics and the effects of additives on storage stability and
      structure of D-psicose 3-epimerase.
AB  - OBJECTIVE: To explore deactivation kinetics and the effects of some additives on
      the activity and conformational changes of D-psicose 3-epimerase (DPEase) during
      its storage. RESULTS: The experimental data of DPEase inactivation during storage
      at 4-45  degrees C fitted with the first-order expression model. The inactivation
      rate constants of DPEase stored at 4, 10, 25, 35 and 45  degrees C were 0.0076,
      0.01, 0.0223, 0.0351 and 0.0605 day, respectively. A regression formula of half
      lives as storage temperatures, ln t 1/2 = 4.7396/T * 103 - 12.536, was obtained.
      MnSO4 at 0.15 g l-1 enhanced the residual activity by 16% after 15 days and 17%
      after 30 days compared with control, but 2 g ascorbic acid l-1 reduced activity
      by 69 and 58% at the same time. In addition, 0.15 g MnSO4 l-1 and 20 g ethylene
      glycol l-1 maintained the secondary and tertiary structure of DPEase.
      CONCLUSIONS: MnSO4 and ethylene glycol actively promoted the storage and
      conformational stability of DPEase. In contrast, ascorbic acid was
      disadvantageous.

PMID- 29038927
TI  - Novel strategy for phenyllactic acid biosynthesis from phenylalanine by whole
      cell recombinant Escherichia coli coexpressing L-phenylalanine oxidase and L
      lactate dehydrogenase.
AB  - OBJECTIVES: To enhance the efficiency of phenyllactic acid (PLA) production from
      L-phenylalanine (L-Phe) by introducing a novel artificial pathway into
      Escherichia coli RESULTS: The production of PLA from L-Phe by recombinant E. coli
      (ldh-lpox) coexpressing L-phenylalanine oxidase and L-lactate dehydrogenase was
      studied. The new PLA synthesis pathway was confirmed to be efficient in
      recombinant E. coli. Subsequently, two different biocatalyst processes were
      carried out and optimized for PLA production. In the whole cell biosynthesis
      process at high cell density using collected recombinant cells as catalyst, at
      optimal conditions (L-Phe 6 g/l, pH 7.5, 35  degrees C, CDW 24.5 g/l and 200
      rpm), the recombinant E. coli (ldh-lpox) produced 1.62 g PLA/l with a conversion
      of 28% from L-Phe. Similarly, during the two-temperature-stage fermentation
      process in flasks using IPTG-induced cells, the temperature in the second stage
      was increased to 35  degrees C to benefit the biocatalyst process, and comparable
      phenyllactic acid production of 1.47 g/l was obtained from 12 g L-Phe/l.
      CONCLUSIONS: Recombinant E. coli (ldh-lpox) was efficient in PLA production
      realizing a high titer of several folds compared with studies using L-Phe as
      substrate.

PMID- 29038928
TI  - Characterization and mutation analysis of a halotolerant serine protease from a
      new isolate of Bacillus subtilis.
AB  - OBJECTIVES: A bacterial halotolerant enzyme was characterized to understand the
      molecular mechanism of salt adaptation and to explore its protein engineering
      potential. RESULTS: Halotolerant serine protease (Apr_No16) from a newly isolated
      Bacillus subtilis strain no. 16 was characterized. Multiple alignments with
      previously reported non-halotolerant proteases, including subtilisin Carlsberg,
      indicated that Apr_No16 has eight acidic or polar amino acid residues that are
      replaced by nonpolar amino acids in non-halotolerant proteases. Those residues
      were hypothesized to be one of the primary contributors to salt adaptation. An
      eightfold mutant substituted with Ala residues exhibited 1.2- and 1.8-fold
      greater halotolerance at 12.5% (w/v) NaCl than Apr_No16 and Carlsberg,
      respectively. Amino acid substitution notably shifted the theoretical pI of the
      eightfold mutant, from 6.33 to 9.23, compared with Apr_No16. The resulting
      protein better tolerated high salt conditions. CONCLUSIONS: Changing the pI of a
      bacterial serine protease may be an effective strategy to improve the enzyme's
      halotolerance.

PMID- 29038929
TI  - Validating a Culturally-sensitive Social Competence Training Programme for
      Adolescents with ASD in a Chinese Context: An Initial Investigation.
AB  - Previous studies on social skills training on ASD were done almost exclusively in
      the West with children as the main subjects. Demonstrations of the applicability
      of social interventions in different cultures and age groups are warranted. The
      current study outlined the development and preliminary evaluation of a CBT
      context-based social competence training for ASD (CBT-CSCA) developed in Hong
      Kong for Chinese adolescents with ASD. Twenty-five adolescents (aged 12-17 years,
      with a FSIQ above 80) were recruited. Significant improvements in social
      competence, autistic symptoms and general psychopathology at post-training and 3
      month follow-up were reported by the parents. The study provided initial evidence
      support to the applicability of social competence training for adolescents with
      ASD in a different culture.

PMID- 29038931
TI  - Brief Report: Body Image in Autism: Evidence from Body Size Estimation.
AB  - Individuals with autism spectrum disorder (ASD) have difficulties with social
      interaction and communication. First-hand accounts written by individuals with
      ASD have shown the existence of other atypical characteristics such as
      difficulties with body awareness. However, few studies have examined whether such
      atypicalities are found more generally among individuals with ASD. We examined
      body image (i.e., self-body awareness) by asking individuals with ASD and
      typically developing (TD) individuals to estimate their own body size (shoulder
      width). Results show that TD individuals estimated their shoulder width more
      accurately than individuals with ASD. This study suggests that individuals with
      ASD often experience misperceptions in their body size.

PMID- 29038930
TI  - Verbal Ability and Psychiatric Symptoms in Clinically Referred Inpatient and
      Outpatient Youth with ASD.
AB  - Youth with autism spectrum disorder (ASD) experience high rates of psychiatric
      symptoms, but the relation between verbal ability and psychiatric symptoms is
      unknown. This study utilized a large sample of clinically referred inpatient and
      outpatient youth with ASD to compare psychiatric comorbidity between verbal and
      minimally-verbal youth, adjusting for nonverbal IQ, age, and ASD symptom
      severity. Results indicated that verbal youth were more likely to present with
      and meet clinical cutoffs for depression and oppositional defiant disorder
      symptoms, with greater impairment associated with depression. Youth in inpatient
      settings had greater symptom severity and impairment across almost all
      psychiatric comorbidities. These results present the most direct estimate to date
      of the association between verbal ability and psychiatric comorbidity in ASD.

PMID- 29038932
TI  - MR T2 value of the tibial nerve can be used as a potential non-invasive and
      quantitative biomarker for the diagnosis of diabetic peripheral neuropathy.
AB  - OBJECTIVE: To determine the role of quantitative tibial nerve T2 value in the
      diagnosis of diabetic peripheral neuropathy (DPN). METHODS: MR imaging and T2
      mapping of the tibial nerve were performed in 22 diabetic patients with DPN, 20
      diabetic patients without DPN and 20 healthy controls. Nerve T2 values were
      measured, and compared using the Mann-Whitney U test. Receiver operating
      characteristic (ROC) curve analysis was used to determine the diagnostic ability
      of T2 value to identify DPN. RESULTS: Nerve T2 value was 55.06 +/- 4.05 ms, 48.91
      +/- 3.06 ms and 45.61 +/- 1.86 ms in patients with DPN, patients without DPN and
      controls, respectively. Patients with DPN had significantly higher nerve T2
      values than patients without DPN (P < 0.001). Nerve T2 values in patients without
      DPN were higher than in controls (P < 0.001). ROC analysis showed that T2 values
      had a diagnostic sensitivity of 81.8 %, specificity of 89.2 % and area under the
      curve of 0.922 for identifying patients with DPN from patients without DPN plus
      controls when the cutoff point was 51.34 ms. CONCLUSION: T2 value of the tibial
      nerve can be used as an alternative, non-invasive quantitative parameter to
      assess DPN in diabetic patients. KEY POINTS: * Tibial nerves in patients with DPN
      showed T2 hyperintensity and enlargement. * Tibial nerves in patients with DPN
      had an increased T2 value. * T2 value might be used as a quantitative biomarker
      for DPN.

PMID- 29038933
TI  - Volume doubling time of lung cancer detected in idiopathic interstitial
      pneumonia: comparison with that in chronic obstructive pulmonary disease.
AB  - OBJECTIVES: To assess the volume doubling time (VDT) of lung cancers in IIP
      compared with COPD. METHODS: A total of 61 patients (32 with IIP and 29 with
      COPD) were identified. A radiologist performed three-dimensional manual
      segmentation for lung cancers. VDTs were calculated and compared between two
      groups. Logistic regression was performed to identify factors associated with
      rapid tumour growth (VDT < 90 days). RESULTS: The median VDT of lung cancers in
      IIP (78.2 days) was significantly shorter than that in COPD (126.1 days;
      p=0.004). Squamous cell carcinoma (SqCC) was the most frequent subtype, followed
      by small cell lung cancer (SCLC) in IIP. In COPD, SqCC was the most frequent
      subtype, followed by adenocarcinoma. Rapid tumour growth was observed in 20
      cancers from IIP, and in nine cancers from COPD (p=0.021). SCLC was significantly
      correlated with rapid tumour growth (p=0.038). Multivariate analysis revealed
      that the presence of IIP was the single independent predictor of rapid tumour
      growth (p = 0.016; odds ratio, 3.7). CONCLUSIONS: Lung cancers in IIP showed more
      rapid growth, with median VDT < 90 days. Therefore, a shorter follow-up interval
      (<90 days) may be necessary when CT surveillance is considered in IIP patients
      with suspected lung cancer. KEY POINTS: * The median VDTs of lung cancers in IIP
      was 78.2 days. * Rapid tumour growth occurred more frequently in IIP than in
      COPD. * IIP was the single independent predictor of rapid tumour growth. *
      Shorter CT follow-up interval may be necessary in IIP with suspicious nodules.

PMID- 29038934
TI  - Characterisation of fibrosis in chemically-induced rat mammary carcinomas using
      multi-modal endogenous contrast MRI on a 1.5T clinical platform.
AB  - OBJECTIVES: To determine the ability of multi-parametric, endogenous contrast MRI
      to detect and quantify fibrosis in a chemically-induced rat model of mammary
      carcinoma. METHODS: Female Sprague-Dawley rats (n=18) were administered with N
      methyl-N-nitrosourea; resulting mammary carcinomas underwent nine-b-value
      diffusion-weighted (DWI), ultrashort-echo (UTE) and magnetisation transfer (MT)
      magnetic resonance imaging (MRI) on a clinical 1.5T platform, and associated
      quantitative MR parameters were calculated. Excised tumours were histologically
      assessed for degree of necrosis, collagen, hypoxia and microvessel density.
      Significance level adjusted for multiple comparisons was p=0.0125. RESULTS:
      Significant correlations were found between MT parameters and degree of
      picrosirius red staining (r > 0.85, p < 0.0002 for ka and delta, r < -0.75, p <
      0.001 for T1 and T1s, Pearson), indicating that MT is sensitive to collagen
      content in mammary carcinoma. Picrosirius red also correlated with the DWI
      parameter fD* (r=0.801, p=0.0004) and conventional gradient-echo T2* (r=-0.660,
      p=0.0055). Percentage necrosis correlated moderately with ultrashort/conventional
      echo signal ratio (r=0.620, p=0.0105). Pimonidazole adduct (hypoxia) and CD31
      (microvessel density) staining did not correlate with any MR parameter assessed.
      CONCLUSIONS: Magnetisation transfer MRI successfully detects collagen content in
      mammary carcinoma, supporting inclusion of MT imaging to identify fibrosis, a
      prognostic marker, in clinical breast MRI examinations. KEY POINTS: *
      Magnetisation transfer imaging is sensitive to collagen content in mammary
      carcinoma. * Magnetisation transfer imaging to detect fibrosis in mammary
      carcinoma fibrosis is feasible. * IVIM diffusion does not correlate with
      microvessel density in preclinical mammary carcinoma.

PMID- 29038935
TI  - Clinical knowledge of community pharmacists in Croatia for detecting drug-related
      problems.
AB  - Background Drug-related problems (DRPs) interfere with patient's health outcomes
      and have a negative impact on healthcare resources. Successful management of DRPs
      is an essential part of pharmaceutical care. Pharmacists should have adequate
      clinical knowledge in order to effectively implement pharmaceutical care and
      manage DRPs. Objective To determine the clinical knowledge of community
      pharmacists in Croatia to detect and resolve DRPs. Method A sample of 302
      community pharmacists have anonymously and voluntarily completed the validated
      survey-based clinical knowledge measurement tool. For each completed survey, all
      statements were scored individually, and a total score was calculated. The lowest
      possible total score was 0 and the highest was 80. Higher survey score indicates
      a higher level of clinical knowledge to detect and resolve a DRP. Results All
      community pharmacists had a mean score of 45.5 +/- 8.6, while pharmacists from a
      pharmacy chain with mandatory education had a higher mean score of 50.2 +/- 6.5.
      Multivariate linear regression revealed that only additional education (beta =
      0.272, p < 0.001) is associated with a higher mean score, while age and gender
      have no influence on the survey score. Conclusion Additional education of
      community pharmacists could increase their clinical knowledge to detect and
      resolve DRPs.

PMID- 29038936
TI  - Current practice and opinions of hospital pharmacists regarding their role in the
      screening, prevention and treatment of delirium.
AB  - Background An interdisciplinary approach is fundamental for effective prevention
      and treatment of delirium. Pharmacists could play a role in identifying and
      resolving medication-related delirium. However, little is known about their role
      in delirium care. Objective The main purpose of this survey was to assess the
      current practice and opinions of pharmacists concerning their involvement in
      screening, prevention and treatment of delirium. Setting Pharmacists in public
      and private hospitals in Australia. Method A cross-sectional survey was conducted
      using a pilot tested web-based questionnaire which was distributed primarily via
      a link in the electronic newsletter of the Society of Hospital Pharmacists of
      Australia. Main outcome measure Number and proportion of respondents answering
      questions related to the practice and perceptions of pharmacists in delirium
      management. Results Responses from 106 pharmacists were included in the analysis.
      Most respondents believed that pharmacists could play a role in prevention (92%)
      and screening (62%) of patients for delirium. However, in practice only 8% of
      pharmacists reported that they had ever screened a patient for delirium using a
      validated tool and 79% indicated that pharmacists were never or rarely involved
      in delirium treatment. When pharmacists did make recommendations half of the
      respondents said that pharmacists' recommendations were frequently or always
      accepted by the delirium treating teams. Conclusion Hospital pharmacists are
      underutilised in the prevention and management of delirium. Strategies to
      increase their involvement in the prevention and management of delirium should be
      implemented.

PMID- 29038937
TI  - Resurrecting the Empathy-Bullying Relationship with a Pro-Bullying Attitudes
      Mediator: the Lazarus Effect in Mediation Research.
AB  - The purpose of this study was to determine whether pro-bullying attitudes are
      capable of mediating the low empathy-bullying relationship in the absence of a
      significant unmediated correlation between low empathy and bullying behavior.
      Using three waves of self-report data from 1371 (677 boys, 694 girls) pre
      adolescent/early adolescent members of the Illinois Study of Bullying and Sexual
      Violence (ISBSV), the mediating effect of pro-bullying attitudes on the low
      empathy-bullying connection was examined. A path analysis revealed that pro
      bullying attitudes successfully mediated the pathway running from low empathy to
      bully perpetration even though the unmediated relationship between low empathy
      and bullying perpetration was non-significant. A control or comparison pathway
      running from bully perpetration to pro-bullying attitudes to low empathy was also
      tested and found to be non-significant. It would appear that low empathy
      contributes to bullying perpetration by stimulating pro-bullying attitudes which,
      in turn, promote bullying perpetration. The theoretical, research, and practical
      implications of these results are discussed.

PMID- 29038938
TI  - A Secure Base from which to Cooperate: Security, Child and Parent Willing Stance,
      and Adaptive and Maladaptive Outcomes in two Longitudinal Studies.
AB  - Early secure attachment plays a key role in socialization by inaugurating a long
      term mutual positive, collaborative interpersonal orientation within the parent
      child dyad. We report findings from Family Study (community mothers, fathers, and
      children, from age 2 to 12, N = 102, 51 girls) and Play Study (exclusively low
      income mothers and children, from age 3.5 to 7, N = 186, 90 girls). We examined
      links among observed secure attachment at toddler age, child and parent
      receptive, willing stance to each other, observed in parent-child contexts at
      early school age, and developmental outcomes. The developmental outcomes included
      parent-rated child antisocial behavior problems and observed positive mutuality
      with regard to conflict issues at age 12 in Family Study, and mother-rated child
      antisocial behavior problems and observed child regard for rules and moral self
      at age 7 in Play Study. In mother-child relationships, the child's willing stance
      mediated indirect effects of child security on positive mutuality in Family Study
      and on all outcomes in Play Study. In father-child relationships, both the
      child's and the parent's willing stance mediated indirect effects of child
      security on both outcomes. Early security initiates an adaptive developmental
      cascade by enlisting the child and the parent as active, willingly receptive and
      cooperative agents in the socialization process. Implications for children's
      parenting interventions are noted.

PMID- 29038939
TI  - Effect of Cobalt on Sperm Motility in an Endangered Trout Species, Salmo
      coruhensis.
AB  - Experiments were designed to examine the in vitro effect of cobalt on sperm
      motility of the endangered trout species (Salmo coruhensis). Sperm samples were
      diluted in an immobilizing solution, and activated in a motility-activation
      solution that was supplemented with cobalt at concentrations of 1, 10, 100 and
      1000 mg/L. The percentage of motile sperm and duration of motility were
      determined. Cobalt concentrations of 1-100 mg/L had a positive effect on the
      percentage of motile sperm and duration of motility compared to the control
      group, while a concentration of 1000 mg/L resulted in decreases in these
      parameters (p < 0.05). The percentages of motile sperm at cobalt concentrations
      of 0, 1, 10, 100 and 1000 mg/L were 83.33% +/- 0.25%, 88.33% +/- 0.34%, 89.00% +/
      0.57%, 90.00% +/- 0.87% and 42.50% +/- 0.45%, respectively; and the time
      durations over which the sperm remained motile were 72.00 +/- 0.63, 74.83 +/-
      0.28, 77.40 +/- 0.47, 81.14 +/- 0.78, and 50.25 +/- 0.67 s, respectively. This
      study has shown that sperm motility and duration were significantly enhanced (p <
      0.05) at cobalt concentrations of 1, 10 and 100 mg/L, relative to controls, and
      significantly decreased at 1000 mg/L.

PMID- 29038940
TI  - Impact of Saw Dust Application on the Distribution of Potentially Toxic Metals in
      Contaminated Soil.
AB  - The need to develop an approach for the reclamation of contaminated site using
      locally available agricultural waste has been considered. The present study
      investigated the application of sawdust as an effective amendment in the
      immobilization of potentially toxic metals (PTMs) by conducting a greenhouse
      experiment on soil collected from an automobile dumpsite. The amended and non
      amended soil samples were analyzed for their physicochemical parameters and
      sequential extraction of PTMs. The results revealed that application of amendment
      had positive impact on the physicochemical parameters as organic matter content
      and cation exchange capacity increased from 12.1% to 12.8% and 16.4 to 16.8
      meq/100 g respectively. However, the mobility and bioavalability of these metals
      was reduced as they were found to be distributed mostly in the non-exchangeable
      phase of soil. Therefore, application of sawdust successfully immobilized PTMs
      and could be applied for future studies in agricultural soil reclamation.

PMID- 29038941
TI  - Spatial and Temporal Heavy Metal Distribution and Surface Water Characterization
      of Kanjli Wetland (a Ramsar site), India Using Different Indices.
AB  - Suitability of surface water of Kanjli wetland, Punjab (India) during the period
      of 2013-2015 was assessed for drinking, irrigation and aquatic life using a water
      quality index (WQI), heavy metal pollution index (HPI) and aquatic toxicity index
      (ATI). WQI was calculated using 14 physico-chemical parameters while HPI
      determination used nine heavy metals like As, Cd, Co, Cr, Cu, Fe, Mn, Pb and Zn.
      WQI revealed that Kanjli wetland contained medium quality water (irrigation and
      aquatic life). Cr, Cd and Co exceeded desirable limits of World Health
      Organization (WHO, Guidelines for drinking-water quality, World Health
      Organization, Geneva, 2011) and Indian drinking water standard (2012) during all
      the three seasons (monsoon, post monsoon and winter). HPI values from all sites
      exceeded critical pollution index value of 100 during monsoon season. Few sites
      were unsuitable for normal fish life as per ATI. The study recommends planned
      spatial, temporal and periodic monitoring of wetland using WQI and HPI to sustain
      good water quality (drinking, irrigation and aquatic life).

PMID- 29038943
TI  - A Lower Limb-Pelvis Finite Element Model with 3D Active Muscles.
AB  - A lower limb-pelvis finite element (FE) model with active three-dimensional (3D)
      muscles was developed in this study for biomechanical analysis of human body. The
      model geometry was mainly reconstructed from a male volunteer close to the
      anthropometry of a 50th percentile Chinese male. Tissue materials and structural
      features were established based on the literature and new implemented
      experimental tests. In particular, the muscle was modeled with a combination of
      truss and hexahedral elements to define its passive and active properties as well
      as to follow the detailed anatomy structure. Both passive and active properties
      of the model were validated against the experiments of Post-Mortem Human
      Surrogate (PMHS) and volunteers, respectively. The model was then used to
      simulate driver's emergency braking during frontal crashes and investigate Knee
      Thigh-Hip (KTH) injury mechanisms and tolerances of the human body. A significant
      force and bending moment variance was noted for the driver's femur due to the
      effects of active muscle forces during emergency braking. In summary, the present
      lower limb-pelvis model can be applied in various research fields to support
      expensive and complex physical tests or corresponding device design.

PMID- 29038942
TI  - Fitting structure to function in gene regulatory networks.
AB  - Cascades of transcriptional regulation are the common source of the forward drive
      in all developmental systems. Increases in complexity and specificity of gene
      expression at successive stages are based on the collaboration of varied
      combinations of transcription factors already expressed in the cells to turn on
      new genes, and the logical relationships between the transcription factors acting
      and becoming newly expressed from stage to stage are best visualized as gene
      regulatory networks. However, gene regulatory networks used in different
      developmental contexts underlie processes that actually operate through different
      sets of rules, which affect the kinetics, synchronicity, and logical properties
      of individual network nodes. Contrasting early embryonic development in flies and
      sea urchins with adult mammalian hematopoietic development from stem cells, major
      differences are seen in transcription factor dosage dependence, the silencing or
      damping impacts of repression, and the impact of cellular regulatory history on
      the parts of the genome that are accessible to transcription factor action in a
      given cell type. These different features not only affect the kinds of models
      that can illuminate developmental mechanisms in the respective biological
      systems, but also reflect the evolutionary needs of these biological systems to
      optimize different aspects of development.

PMID- 29038944
TI  - Environmental Lead and Wild Birds: A Review.
AB  - Lead is a persistent inorganic environmental pollutant that affects humans and
      animals worldwide. Avian species are especially susceptible to lead exposure
      through consumption of lead ammunition, lead fishing tackle, and other
      contaminated food sources such as aquatic species ingesting lead contaminated
      sediments in mining areas. Even with government regulations on the use of lead
      ammunition in many countries, including the United States, terrestrial, aquatic,
      predatory, and scavenger avian species are still at risk of exposure to
      potentially lethal concentrations of lead. The toxicities seen in these avian
      species include increased oxidative stress and decreased anti-oxidant enzymes in
      hepatic and renal tissue. The avian immune system is also a target of lead and
      displays a number of altered functions suggestive of immune suppression; however,
      studies in wildlife and laboratory species remain too limited for definitive
      statements with regard to population risk. In contrast, lead clearly inhibits
      reproductive capabilities in adult birds, and alters growth and development of
      hatchlings. Environmental remediation for lead removal, which would lower toxic
      exposure in wildlife, presently is a monumental and prohibitively expensive
      effort. Wildlife exposure will therefore continue in contaminated areas,
      necessitating development of new remediation practices. These plans should aim
      toward limiting more widespread or heavier contamination of wildlife habitats.
      This chapter reviews presently available information of lead toxicity in wild
      bird species, and suggests continued monitoring and reduction strategies to
      reduce lead exposure for at-risk avian populations.

PMID- 29038945
TI  - Human germline editing: a historical perspective.
AB  - The development of the genome editing system called CRISPR-Cas9 has opened a huge
      debate on the possibility of modifying the human germline. But the types of
      changes that could and/or ought to be made have not been discussed. To cast some
      light on this debate, I will describe the story of the CRISPR-Cas9 system. Then,
      I will briefly review the projects for modification of the human species that
      were discussed by biologists throughout the twentieth century. Lastly, I will
      show that for plenty of reasons, both scientific and societal, germline
      modification is no longer a priority for our societies.

PMID- 29038947
TI  - Analysis of hematological parameters in patients treated with ketogenic diet due
      to drug-resistant epilepsy.
AB  - Benefits of the ketogenic diet (KD) in epileptic patients are well known while
      less is known about the nutritional risks of the diet and its potential impacts
      on biochemical nutritional status. In this study, we aimed to evaluate the
      hematological parameters of patients who have drug-resistant epilepsy and are
      treated with KD. Fifty-three patients with drug-resistant epilepsy (mean age 7.4
      +/- 4.4 years [2-18], 23 [43.4%] female) were included in the study. Demographic
      and laboratory data of the patients were retrospectively analyzed at baseline and
      Month 6 and Month 12 of the treatment. Repeated measures ANOVA (post hoc
      Bonferroni correction) and Friedman test were used to assess the changes in data
      during the treatment. Mean hemoglobin levels increased by 0.594 g/dL after 6
      months (p = 0.001) and by 0.602 g/dL after 12 months of the treatment (p =
      0.002). Mean hematocrit level was found to be significantly increased at Month 6
      and 12 of the treatment compared to baseline [F(2,94) = 8.9, p < 0.0001]. An
      increase in MCV levels was determined with the KD treatment [F(2,94) = 19.7, p <
      0.0001]. Mean level of vitamin B12 was found to be significantly increased in
      Month 12 of treatments compared to Month 6 [F(1.686,72.479) = 3.472, p = 0.035].
      There was no significant effect of KD on other hematological parameters (red
      blood cell, white blood cell and platelet counts, serum iron, total iron-binding
      capacity, transferrin saturation, and ferritin and folic acid levels). We can
      conclude that KD increases levels of hemoglobin, hematocrit, MCV, and serum
      vitamin B12 in patients with intractable epilepsy. Prospective, multi-center,
      longitudinal studies are needed to confirm our results.

PMID- 29038946
TI  - Cognitive and behavioral disorders in Parkinson's disease: an update. II:
      behavioral disorders.
AB  - Patients with Parkinson's disease (PD) can experience several behavioral
      symptoms, such as apathy, agitation, hypersexuality, stereotypic movements,
      pathological gambling, abuse of antiparkinsonian drugs, and REM sleep behavioral
      disorders. Psychoses and hallucinations, depression and anxiety disorders, and
      difficulties in recognizing and experiencing emotions also impair behavior and
      can cause severe psychosocial problems in patients with PD. Symptoms can be
      present since early stages of the disease, sometimes even before the appearance
      of classical motor symptoms, likely in relation to dopamine depletion in basal
      ganglia and/or to dysfunctions of other neurotrasmitter systems, and others can
      develop later, in some cases in relation to dopaminergic treatment. In this
      paper, we review recent literature, with particular attention to the last 5
      years, on the main behavioral and emotional disturbances described in PD patients
      as well as the hypothesized neurofunctional substrate of such impairments.
      Finally, we provide some suggestions on the most suitable instruments to check
      and assess PD-associated behavioral defects over time.

PMID- 29038948
TI  - Molecular characterization of NBS-LRR genes in the soybean Rsv3 locus reveals
      several divergent alleles that likely confer resistance to the soybean mosaic
      virus.
AB  - KEY MESSAGE: The divergence patterns of NBS - LRR genes in soybean Rsv3 locus
      were deciphered and several divergent alleles ( NBS_C, NBS_D and Columbia NBS_E )
      were identified as the likely functional candidates of Rsv3. The soybean Rsv3
      locus, which confers resistance to the soybean mosaic virus (SMV), has been
      previously mapped to a region containing five nucleotide binding site-leucine
      rich repeats (NBS-LRR) genes (referred to as nbs_A-E) in Williams 82. In
      resistant cultivars, however, the number of NBS-LRR genes in this region and
      their divergence from susceptible alleles remain unclear. In the present study,
      we constructed and screened a bacterial artificial chromosome (BAC) library for
      an Rsv3-possessing cultivar, Zaoshu 18. Sequencing two positive BAC inserts on
      the Rsv3 locus revealed that Zaoshu 18 possesses the same gene content and order
      as Williams 82, but two of the NBS-LRR genes, NBS_C and NBS_D, exhibit distinct
      features that were not observed in the Williams 82 alleles. Obtaining these NBS
      LRR genes from eight additional cultivars demonstrated that the NBS_A-D genes
      diverged into two different alleles: the nbs_A-D alleles were associated with the
      rsv3-type cultivars, whereas the NBS_A-D alleles were associated with the Rsv3
      possessing cultivars. For the NBS_E gene, the cultivar Columbia possesses an
      allele (NBS_E) that differed from that in Zaoshu 18 and rsv3-type cultivars
      (nbs_E). Exchanged fragments were further detected on alleles of the NBS_C-E
      genes, suggesting that recombination is a major force responsible for allele
      divergence. Also, the LRR domains of the NBS_C-E genes exhibited extremely strong
      signals of positive selection. Overall, the divergence patterns of the NBS-LRR
      genes in Rsv3 locus elucidated by this study indicate that not only NBS_C but
      also NBS_D and Columbia NBS_E are likely functional alleles that confer
      resistance to SMV.

PMID- 29038949
TI  - Sleep disorders and health-related quality of life in patients with interstitial
      lung disease.
AB  - BACKGROUND: Interstitial lung diseases (ILD) are chronic and restrictive lung
      diseases with poor survival and quality of life. The aim of this study was to
      investigate the frequency of sleep disorders in idiopathic pulmonary fibrosis
      (IPF) and sarcoidosis and to assess patients' quality of life in relation to
      these disorders. METHODS: Forty patients, 19 with IPF, and 21 with sarcoidosis
      stage II/III were included. They were compared with 15 healthy subjects. All
      patients performed all-night polysomnography (PSG) and completed the Epworth,
      Berlin, and Stop-Bang questionnaires. In order to evaluate the quality of life,
      all patients completed the Short-Form 36 (SF-36) questionnaire. RESULTS: Of the
      IPF patients, 68% were diagnosed with mild obstructive sleep apnea (OSA), 5.2%
      with moderate to severe, 5.2% with severe OSA, and 21% with no OSA. Of patients
      with sarcoidosis, 52.4% were diagnosed with mild OSA and 4.8% with moderate
      severity OSA. The remaining 42.8% did not have OSA. The health-related quality of
      life in both patients with IPF and patients with sarcoidosis was impaired
      especially in the domains concerning physical health and the level of
      independence, compared to the control group. CONCLUSIONS: In this sample of
      patients with IPF and sarcoidosis, obstructive sleep apnea is common at least in
      a mild degree of severity. The SF-36 questionnaire may be a useful tool for the
      evaluation of the quality of life in these patients.

PMID- 29038950
TI  - Firing a loaded gun during sleep in an elderly man with a "perfect storm" of risk
      factors including severe obstructive sleep apnea.
AB  - PURPOSE: We report a case of firing a loaded gun during sleep in a geriatric
      patient with undiagnosed major sleep disorders and multiple risk factors for
      sleep violence. Polysomnographic findings, diagnostic challenges, and forensic
      implications in this unprecedented geriatric case are discussed. METHODS: A 75
      year-old employed man, married for 32 years, presented to a sleep center
      reporting to having fired a shot in his bedroom during sleep while his wife was
      away, without memory of hearing the gunshot. The day before the event, the
      patient had a normal life, apart from serious worries about recent nearby
      burglaries that prompted his sleeping with a loaded gun placed behind his bed.
      The patient underwent a sleep medicine workup, including nocturnal video
      polysomnography (vPSG). RESULTS: The patient and his wife were unaware of any
      sleep problems. Upon careful questioning, only mild daytime sleepiness and rare
      episodes of minor abnormal motor behavior were reported. At vPSG, sleep structure
      was markedly disrupted with only one clear sleep cycle with REM sleep that had
      preserved REM-atonia; severe obstructive sleep apnea and moderately severe
      periodic limb movement activity were documented. Brief abnormal movements from
      REM sleep without apparent precipitant were recorded. CPAP therapy was effective.
      CONCLUSIONS: In this case, there was a "perfect storm" of sleep and psychological
      risk factors that converged to strongly promote precipitous arousals with sleep
      related violence in a patient with documented sleep motor dyscontrol. Primary
      care physicians, including geriatric specialists, should question patients and
      their spouses about any symptoms of sleep disorders.

PMID- 29038954
TI  - An unusual blood pressure reading.

PMID- 29038953
TI  - Current Concepts in Rehabilitation for Traumatic Anterior Shoulder Instability.
AB  - PURPOSE OF REVIEW: The objectives of this review are to evaluate the current
      evidence-based literature and concepts surrounding rehabilitation in patients
      with anterior shoulder instability injuries and surgical repair. RECENT FINDINGS:
      The current literature evidence for shoulder rehabilitation for anterior shoulder
      instability and labral repair is limited. As a result, there are variations among
      surgeons and physical therapists in rehabilitation protocols after anterior
      shoulder instability injuries and repair. While general consensus on certain
      rehabilitation parameters exists, the evidence for the importance of
      rehabilitation and functional performance test for return to sport in future
      injury prevention is still lacking in literature. Rehabilitation after anterior
      shoulder instability injury and anterior labral repair is paramount in the
      injured or post-operative shoulder. Restoration of soft tissue mobility, dynamic
      glenohumeral joint stability, and balance and strength around the shoulder not
      only protect healing of injured or repaired soft tissues but also potentially
      minimizes future re-injury or recurrence risk.

PMID- 29038951
TI  - The Epidemiology and Natural History of Anterior Shoulder Instability.
AB  - PURPOSE OF REVIEW: The purpose of this review is to outline the natural history
      and best clinical practices for nonoperative management of anterior shoulder
      instability. RECENT FINDINGS: Recent studies continue to demonstrate a role for
      nonoperative treatment in the successful long-term management of anterior
      glenohumeral instability. The success of different positions of shoulder
      immobilization is reviewed as well. There are specific patients who may be best
      treated with nonoperative means after anterior glenohumeral instability. There
      are also patients who are not good nonoperative candidates based on a number of
      factors that are outlined in this review. There continues to be no definitive
      literature regarding the return to play of in-season athletes. Successful
      management requires a thorough understanding of the epidemiology, pathoanatomy,
      history, physical examination, diagnostic imaging modalities, and natural history
      of operative and nonoperative treatment.

PMID- 29038952
TI  - Lateral Lumbar Interbody Fusion-Outcomes and Complications.
AB  - PURPOSE OF REVIEW: Lateral lumbar interbody fusion (LLIF) is a relatively new,
      minimally invasive technique for interbody fusion. The goal of this review is to
      provide a general overview of LLIF with a special focus on outcomes and
      complications. RECENT FINDINGS: Since the first description of the technique in
      2006, the indications for LLIF have expanded and the rate of LLIF procedures
      performed in the USA has increased. LLIF has several theoretical advantages
      compared to other approaches including the preservation of the anterior and
      posterior annular/ligamentous structures, insertion of wide cages resting on the
      dense apophyseal ring bilaterally, and augmentation of disc height with indirect
      decompression of neural elements. Favorable long-term outcomes and a reduced risk
      of visceral/vascular injuries, incidental dural tears, and perioperative
      infections have been reported. However, approach-related complications such as
      motor and sensory deficits remain a concern. In well-indicated patients, LLIF can
      be a safe procedure used for a variety of indications.

PMID- 29038955
TI  - Frontoethmoidal encephalocele: a pediatric airway challenge.

PMID- 29038956
TI  - Interaction of Leptospira with the Innate Immune System.
AB  - Innate immunity encompasses immediate host responses that detect and respond to
      microbes. Besides recognition by the complement system (see the chapter by A.
      Barbosa, this volume), innate immunity concerns cellular responses. These are
      triggered through recognition of conserved microbial components (called MAMPs) by
      pattern recognition receptors (PRRs), leading, through secretion of cytokines,
      antimicrobial peptides, and immune mediators, to cellular recruitment and
      phagocytosis. Leptospira spp. are successful zoonotic pathogenic bacteria that
      obviously overcome the immune system of their hosts. The first part of this
      chapter summarizes what is known about leptospires recognition and interaction
      with phagocytes and other innate immune cells, and the second part describes
      specific interactions of leptospiral MAMPs with PRRs from the TLR and NLR
      families. On the one hand, pathogenic leptospires appear to escape macrophage and
      neutrophil phagocytosis. On the other hand, studies about PRR sensing of
      leptospires remain very limited, but suggest that pathogenic leptospires escape
      some of the PRRs in a host-specific manner, due to peculiar cell wall
      specificities or post-translational modifications that may impair their
      recognition. Further studies are necessary to clarify the mechanisms and
      consequences of leptospiral escape on phagocytic functions and hopefully give
      clues to potential therapeutic strategies aimed at restoring the defective
      activation of PRRs by pathogenic Leptospira spp.

PMID- 29038957
TI  - [Infections in rheumatology : Differential diagnosis or complication of
      immunosuppressive therapy].

PMID- 29038958
TI  - Glaucoma following childhood cataract surgery: the South India experience.
AB  - PURPOSE: To determine the characteristics and risk factors for the development of
      glaucoma after cataract surgery in children seen at a major referral tertiary eye
      centre in South India. METHODS: This is a retrospective review of the medical
      records of consecutive patients seen at the glaucoma/paediatric eye clinic of the
      centre, with a diagnosis of glaucoma secondary to aphakia/pseudophakia over a 5
      year period. RESULTS: There were 21 eyes of 14 children that developed glaucoma
      and 23 eyes of 12 children were selected as control. The mean age (standard
      deviation SD) at the time of cataract surgery for the glaucoma group was 7.4 (+/-
      10.1) months and 39.13 (+/- 41.2) months for the control. The mean follow-up (SD)
      period was 114.29 (+/- 61.9) months and 97.61 (+/- 43.5) months for the glaucoma
      and control, respectively. The mean duration from cataract surgery to onset of
      glaucoma was 81.19 (+/- 52.4) months (median 66 months, range 21-172 months).
      Multivariate analysis detected age at surgery younger than 12 months (OR 10.45,
      95%CI 1.76-62.03, p = 0.010) and ocular anomalies mainly microcornea (OR 7.11,
      95%CI 1.14-44.46, p = 0.036) as risk factors for development of glaucoma after
      paediatric cataract surgery. CONCLUSION: Glaucoma can develop several years after
      childhood cataract surgery. Surgery in the first year of life and microcornea are
      risk factors for the development of glaucoma post-surgery. Signs of glaucoma
      should specifically be looked for during follow-up visits.

PMID- 29038959
TI  - The effect of additional trabecular aspiration to phacoemulsification and
      trabectome as a triple procedure in pseudoexfoliation glaucoma: a case-matched
      study.
AB  - BACKGROUND: Trabectome surgery combined with phacoemulsification is effective in
      lowering (intraocular pressure) IOP in pseudoexfoliation glaucoma. Trabectome
      surgery usually aims to remove two to four clock hours of the trabecular
      meshwork. When adding trabecular aspiration, the remaining meshwork can be
      treated as well, and therefore 360 degrees of the meshwork can be reached. This
      study was conducted to investigate the additional benefits and risks of adding
      trabecular aspiration to the combination of phacoemulsification and trabectome as
      a triple procedure. METHODS: Two groups of patients from two centres were
      compared. The first group underwent phacoemulsification and trabectome
      (Freiburg), and the second group underwent additional trabecular aspiration
      (Dusseldorf). Using a case-matched retrospective study design, 50 patients were
      included into each group. The clinical endpoint was the intraocular pressure at
      follow up. RESULTS: The mean follow up was 22 months. Mean intraocular pressure
      decreased in all 100 patients from 25.0 (SD 4.3) to 14.9 mmHg (SD 4.0). Comparing
      the two groups, the IOP reduction was from 25.0 (SD 5.0) to 14.1 (SD 4.4) mmHg in
      the triple procedure group compared to a reduction from 25.0 (3.6) to 15.7 (SD
      3.4) mmHg in the phaco/trabectome group. The difference was statistically
      significant (p = 0.03). The number of medication after surgery was reduced from
      2.2 (SD 0.9) to 1.7 (SD 0.9) while in the phaco/trabectome group the medication
      score was reduced from 2.2 (SD 1.0) to 1.1 (SD 0.1) (p < 0.001). CONCLUSIONS:
      This study shows that the combination of trabectome surgery and
      phacoemulsification leads to a clinically significant reduction of IOP over
      several years in patients with pseudoexfoliation glaucoma. The addition of
      trabecular aspiration as a triple procedure results in further lowering of IOP
      without causing more side effects. This finding might be biased by the higher
      medication score in the triple procedure group.

PMID- 29038960
TI  - Comparison of four 11C-labeled PET ligands to quantify translocator protein 18
      kDa (TSPO) in human brain: (R)-PK11195, PBR28, DPA-713, and ER176-based on recent
      publications that measured specific-to-non-displaceable ratios.
AB  - Translocator protein (TSPO) is a biomarker for detecting neuroinflammation by
      PET. 11C-(R)-PK11195 has been used to image TSPO since the 1980s. Here, we
      compared the utility of four 11C-labeled ligands-(R)-PK11195, PBR28, DPA-713, and
      ER176-to quantify TSPO in healthy humans. For all of these ligands, BP ND
      (specific-to-non-displaceable ratio of distribution volumes) was measured by
      partially blocking specific binding with XNBD173 administration. In high-affinity
      binders, DPA-713 showed the highest BP ND of 7.3 followed by ER176 (4.2), PBR28
      (1.2), and PK11195 (0.8). Only ER176 allows the inclusion of low-affinity binders
      because of little influence of radiometabolites and high BP ND. If inclusion of
      all three genotypes is important for study logistics, ER176 is the best of these
      four radioligands for studying neuroinflammation.

PMID- 29038961
TI  - Association of indirect restorations with past caries history and present need
      for restorative treatment in the Northern Finland Birth Cohort 1966.
AB  - OBJECTIVES: The objective of this study is to examine the prevalence of indirect
      restorations and their association with past caries history and present need for
      restorative treatment among adults in Northern Finland. MATERIALS AND METHODS:
      The study population was a subsample of the Northern Finland Birth Cohort 1966 (n
      = 1961). The oral examinations were performed in 2012-2013. Indirect restorations
      (inlays/onlays and single crowns) were recorded tooth wise. Caries history was
      described with the sum of decayed, missing, and filled teeth (DMF). Caries was
      assessed using the International Caries Detection and Assessment System (ICDAS).
      The score of 4 was used as the cut off point for visible decay. Present need for
      restorative treatment was calculated by summing the decayed (D) and fractured
      (Fr) teeth. Need for restorative treatment was dichotomized to low [(D + Fr) <=
      1] and high [(D + Fr) > 1]. RESULTS: Altogether, 7.8% of the study population had
      indirect restorations. The prevalence of indirect restorations did not differ
      within DMF (p = 0.925), but it was higher among the subjects with a low need for
      restorative treatment (p < 0.001). CONCLUSIONS: Indirect restorations were rare
      in the adult population and found mainly among the subjects with a low need for
      restorative treatment. CLINICAL RELEVANCE: The results of the study can encourage
      dentists to consider more often indirect restorations for subjects with a need
      for restorative treatment.

PMID- 29038962
TI  - A comparative study between traditional fixation with miniplates and modified lag
      screws for the treatment of mandibular fractures.
AB  - OBJECTIVES: The objective of this study is to investigate two internal fixation
      surgical techniques for mandibular fractures in order to compare modified lag
      screw techniques with standard miniplates. MATERIALS AND METHODS: This is an
      observational prospective study. Three hundred eighteen patients were operated on
      for mandibular fractures. The patients were divided into two groups according to
      the type of surgical technique used: modified lag screws (155 patients) and
      traditional miniplates (163 patients). Analyses were made of sociodemographic and
      preoperative variables, the parameters related to the fracture type and
      postoperative data. RESULTS: There were no differences between the two groups
      regarding their sociodemographic characteristics. The modified lag screws were
      primarily used with double fractures, while conventional miniplates were more
      often used with simple fractures. The number of complications was higher with the
      miniplate technique. The unfavorable fractures had an OR of 5.75 due to
      postoperative complications; double fractures had an OR of 8.87 and simple
      fractures an OR of 19.53, which, in both cases, were lower with conventional
      miniplates than with modified lag screws. CONCLUSION: Modified lag screws provide
      a rigid fixation system that is as secure as miniplates, but with greater
      compression between the fragments, less postsurgical gap, faster ossification,
      and fewer postoperative complications. CLINICAL RELEVANCE: The modified screw
      technique is a safe tool that does not require any specific osteosynthesis
      materials not found in a basic traumatology kit and has a lower cost, due to the
      reduced amount of material used.

PMID- 29038963
TI  - Lymph node density as a prognostic predictor in patients with betel nut-related
      oral squamous cell carcinoma.
AB  - OBJECTIVES: Lymph node metastasis in oral squamous cell carcinoma (OSCC) is a
      poor prognostic factor. The histopathologic stage (e.g., pN) is used to evaluate
      the severity of lymph node metastasis; however, the current staging system
      insufficiently predicts survival and recurrence. We investigated clinical
      outcomes and lymph node density (LND) in betel nut-chewing individuals. MATERIAL
      AND METHODS: We retrospectively analyzed 389 betel nut-exposed patients with
      primary OSCC who underwent surgical resection in 2002-2015. The prognostic
      significance of LND was evaluated by overall survival (OS) and disease-free
      survival (DFS) using the Kaplan-Meier method. RESULTS: Kaplan-Meier analyses
      showed that the 5-year OS and DFS rates in all patients were 60.9 and 48.9%,
      respectively. Multivariate analysis showed that variables independently
      prognostic for OS were aged population (hazard ratio [HR] = 1.6, 95% confidence
      interval [95% CI] = 1.1-2.5; P = .025), and cell differentiation classification
      (HR = 2.4, 95% CI = 1.4-4.2; P = .002). In pathologic N-positive patients, a
      receiver operating characteristic (ROC) curve for OS was used and indicated the
      best cutoff of 0.05, and the multivariate analysis showed that LND was an
      independent predictor of OS (HR = 2.2, 95% CI = 1.3-3.7; P = .004). CONCLUSIONS:
      Lymph node density, at a cutoff of 0.05, was an independent predictor of OS and
      DFS. OS and DFS underwent multiple analyses, and LND remained significant. The
      pathologic N stage had no influence in the OS analysis. CLINICAL RELEVANCE: LND
      is a more reliable predictor of survival in betel nut-chewing patients for
      further post operation adjuvant treatment, such as reoperation or adjuvant
      radiotherapy.

PMID- 29038964
TI  - Surgical and oncological outcomes after complete mesocolic excision in right
      sided colon cancer compared with conventional surgery: a retrospective, single
      institution study.
AB  - PURPOSE: The aim of the study was whether complete mesocolic excision (CME) with
      central vascular ligation (CVL) is associated with a survival benefit compared
      with traditional procedure in right-sided colon cancer. METHODS: Overall, 251
      consecutive patients underwent surgery for right colon cancer between 2007 and
      2012. After exclusion, 95 subjects received non-CME surgery before 2010, and 97
      subjects received CME surgery after January 2010, when we started to perform CME
      systematically. The number of lymph nodes, morbidity, and mortality was analyzed.
      Overall survival (OS) and disease-specific survival (DSS) were investigated.
      RESULTS: The median number of examined lymph nodes was 33.28 in the CME group and
      26.92 in the non-CME group, p < 0.001. Postoperative complications were 21.6% in
      the CME group and 17.8% in the non-CME group, without significant difference. One
      out of 192 patients died. Three-year OS was 88% in the CME group and 71% in the
      non-CME group (p = 0.003). In stage II, 3-year DSS was 97% in the CME group and
      86% in the non-CME group. In stage III, the 3-year DSSs in the CME and in the non
      CME groups were 86 and 67%, respectively (p < 0.001). Cox's regression showed
      that CME (p = 0.0012), the number of lymph nodes (p = 0.029), and TNM stage (p <
      0.001) were significant independent predictors of DSS at 3 years. CONCLUSION:
      Surgical standardization of CME with CVL for right-sided colon cancer is
      associated with better staging and prognosis, particularly in UICC stage II and
      III. This study shows that CME is safe and reproducible with acceptable
      morbidity.

PMID- 29038965
TI  - Low risk of complications in patients with first-time acute uncomplicated
      diverticulitis.
AB  - PURPOSE: First-time acute uncomplicated diverticulitis (AUD) has been considered
      to have an increased risk of complication, but the level of evidence is low. The
      aim of the present study was to evaluate the risk of complications in patients
      with first-time AUD and in patients with a history of diverticulitis. METHODS:
      This paper is a population-based retrospective study at Vastmanland's Hospital,
      Vasteras, Sweden, where all patients were identified with a diagnosis of colonic
      diverticular disease ICD-10 K57.0-9 from January 2010 to December 2014. The
      records of all patients were surveyed and patients with a computed tomography
      (CT)-verified AUD were included. Complications defined as CT-verified abscess,
      perforation, colonic obstruction, fistula, or sepsis within 1 month from the
      diagnosis of AUD were registered. RESULTS: Of 809 patients with AUD, 642 (79%)
      had first-time AUD and 167 (21%) had a previous history of AUD with no
      differences in demographic or clinical characteristics. In total, 16 (2%)
      patients developed a complication within 1 month irrespective of whether they had
      a previous history of diverticulitis (P = 0.345). In the binary logistic
      regression analysis, first-time diverticulitis was not associated with increased
      risk of complications (OR 1.58; CI 0.52-4.81). The rate of antibiotic therapy was
      about 7-10% during the time period and outpatient management increased from 7% in
      2010 to 61% in 2014. CONCLUSIONS: The risk for development of complications is
      low in AUD with no difference between patients with first-time or recurrent
      diverticulitis. This result strengthens existing evidence on the benign disease
      course of AUD.

PMID- 29038966
TI  - The Effect of a Behavioral Weight-Loss Intervention on Depressive Symptoms Among
      Latino Immigrants in a Randomized Controlled Trial.
AB  - Evidence of whether behavioral weight-loss interventions reduce depressive
      symptoms among Latino immigrants is limited. The effect of a behavioral weight
      loss intervention on depressive symptoms was assessed using data from a clinical
      trial among Latino immigrants. Participants were randomized to a usual care (UC)
      control (n = 41), case management (CM) alone (n = 84), or CM with community
      health worker support (CM+CHW) (n = 82). Generalized estimating equation models
      were used to compare the impact of each intervention with UC. Effect modification
      by poverty level was further investigated. Overall, treatment groups were not
      significantly associated with 24-month changes in CES-D scores. Among
      participants below the 100% federal poverty level (FPL), those randomized to
      CM+CHW had 24-month CES-D scores significantly lower (Beta coefficient = 0.72;
      95% CI 0.55-0.93) than those in UC (p = 0.01). A behavioral weight-loss
      intervention providing case management and support from a CHW reduced depressive
      symptoms among Latino immigrants below the 100% FPL.

PMID- 29038967
TI  - Morphology and the central nervous system of Eratigena atrica affected by a
      complex anomaly in the anterior part of the prosoma.
AB  - Spider embryogenesis is affected by a range of environmental factors. Any sudden,
      drastic change in the environment may impair spider development, leading to
      various body deformities. In the present study, we analyze changes in the
      morphology and structure of the central nervous system of an Eratigena atrica
      larva, obtained in a teratological experiment in which embryos were exposed to
      alternating temperatures of 14 and 32  degrees C for the first 10 days. The
      studied larva had three pedipalps on the right side of the prosoma (polymely),
      two of which were fused along their entire length (total heterosymely). In
      addition, there was a short, club-shaped stump between the pedipalps.
      Histological analysis confirmed major changes in the structure of the
      subesophageal ganglion, i.e., the fusion of all three ganglia of pedipalps.

PMID- 29038968
TI  - Anti-fibrotic nintedanib-a new opportunity for systemic sclerosis patients?
AB  - Systemic sclerosis is a connective tissue disease characterized by progressive
      skin thickening and a wide spectrum of internal organ involvement. Pathogenesis
      includes vasculopathy, inflammation, and fibrosis. Although immunosuppressants
      such as cyclophosphamide and mycophenolate mofetil have shown some benefit in
      interstitial lung disease management, it is still a major cause of morbi
      mortality in these patients. Therefore, there is a current need for new
      therapies. Here, we report a 65-year-old female patient with limited cutaneous
      systemic sclerosis, anti-topoisomerase-positive and extensive lung disease. The
      patient developed progressive lung fibrosis under several immunosuppressants and
      was started on nintedanib, with clinical and functional stabilization. Nintedanib
      is a tyrosine-kinase inhibitor that blocks several profibrotic pathways,
      inhibiting proliferation and migration of fibroblasts and decreasing the
      synthesis of extracellular matrix proteins. It is approved for idiopathic lung
      fibrosis and has demonstrated good results in inhibiting migration and
      proliferation of systemic sclerosis dermal fibroblasts, constituting a promising
      agent for systemic sclerosis-associated lung fibrosis.

PMID- 29038969
TI  - Microvascular imaging and monitoring of human oral cavity lesions in vivo by
      swept-source OCT-based angiography.
AB  - We report the development of optical coherence tomography- (OCT) based
      angiography (OCTA) to image blood flow within microcirculatory tissue beds in
      human oral cavity in vivo with a field of view at 10 mm * 10 mm. Three
      dimensional (3D) structural and vascular images of labial mucosa tissue are
      obtained at a single 3D acquisition. Pathologic mucosal sites with mouth ulcers
      are examined using the OCT tomograms and angiograms, upon which to monitor the
      lesion healing process over a period of 2 weeks. Quantitative metrics of the
      capillary loop density within the lamina propria layer are evaluated, providing
      statistically significant difference between healthy and diseased conditions over
      time. Furthermore, tissue anatomy and vessel morphology of other susceptible
      sites to ulcer, such as tongue, alveolar mucosa, and labial frenulum, are also
      imaged to demonstrate the promise of the proposed method as a clinically useful
      tool for the diagnosis and monitoring of therapeutic treatment of oral tissue
      abnormalities.

PMID- 29038970
TI  - Enhanced photoinduced antibacterial activity of a BODIPY photosensitizer in the
      presence of polyamidoamines.
AB  - Photosensitizers belonging to the boron-dipyrromethenes (BODIPYs) class were
      recently found endowed with good efficacy in the antibacterial photodynamic
      therapy (aPDT) against both Gram-positive and Gram-negative bacteria. In this
      paper, we report on the remarkable adjuvant effect exerted in this respect by
      linear polyamidoamines (PAAs), a family of moderately basic polymers obtained by
      Michael-type polyaddition of amines to bisacrylamides. Three different PAAs
      (AGMA1, BP-AGMA, and BP-DMEDA) were studied, testing for each two different
      molecular weight samples (8000 and 24000 Da). At nontoxic concentrations (1 or 10
      ug mL-1) all PAAs remarkably improved the killing efficacy of BODIPY upon
      irradiation with a green LED device (range: from 480 to 580 nm with lambdamax =
      525 nm) up to an energy rate of 16.6 J cm-2. A 6-7 log unit decrease in bacteria
      survival was observed with concentrations of BODIPY of 1.0 and 0.1 uM in the case
      of Escherichia coli and Staphylococcus aureus, respectively. The one-way analysis
      of variance (ANOVA) was used to evaluate the statistical significance of
      different treatments (n >= 3). Thus, the PAA-photosensitizer combination warrants
      potentially as a new, effective, and mild method of killing bacteria. Moreover,
      the antibacterial treatment here reported might be successfully applied to defeat
      the bacterial resistance often encountered with many antibacterial drugs owing to
      the double action of this two-component treatment.

PMID- 29038972
TI  - Interactions of plant growth-promoting rhizobacteria and soil factors in two
      leguminous plants.
AB  - Although the rhizomicrobiome has been extensively studied, little is known about
      the interactions between soil properties and the assemblage of plant growth
      promoting microbes in the rhizosphere. Herein, we analysed the composition and
      structure of rhizomicrobiomes associated with soybean and alfalfa plants growing
      in different soil types using deep Illumina 16S rRNA sequencing. Soil pH, P and K
      significantly affected the composition of the soybean rhizomicrobiome, whereas
      soil pH and N had a significant effect on the alfalfa rhizomicrobiome. Plant
      biomass was influenced by plant species, the composition of the rhizomicrobiome,
      soil pH, N, P and plant growth stage. The beta diversity of the rhizomicrobiome
      was the second most influential factor on plant growth (biomass). Rhizomicrobes
      associated with plant biomass were identified and divided into four groups: (1)
      positively associated with soybean biomass; (2) negatively associated with
      soybean biomass; (3) positively associated with alfalfa biomass; and (4)
      negatively associated with alfalfa biomass. Genera assemblages among the four
      groups differentially responded to soil properties; Group 1 and Group 2 were
      significantly correlated with soil pH and P, whereas Group 3 and Group 4 were
      significantly correlated with soil N, K and C. The influence of soil properties
      on the relative abundance of plant biomass-associated rhizomicrobes differed
      between soybean and alfalfa. The results suggest the rhizomicrobiome has a
      pronounced influence on plant growth, and the rhizomicrobiome assemblage and
      plant growth-associated microbes are differentially structured by soil properties
      and leguminous plant species.

PMID- 29038973
TI  - Production of ethylene glycol or glycolic acid from D-xylose in Saccharomyces
      cerevisiae.
AB  - The important platform chemicals ethylene glycol and glycolic acid were produced
      via the oxidative D-xylose pathway in the yeast Saccharomyces cerevisiae. The
      expression of genes encoding D-xylose dehydrogenase (XylB) and D-xylonate
      dehydratase (XylD) from Caulobacter crescentus and YagE or YjhH aldolase and
      aldehyde dehydrogenase AldA from Escherichia coli enabled glycolic acid
      production from D-xylose up to 150 mg/L. In strains expressing only xylB and
      xylD, 29 mg/L 2-keto-3-deoxyxylonic acid [(S)-4,5-dihydroxy-2-oxopentanoic acid]
      (2K3DXA) was produced and D-xylonic acid accumulated to ca. 9 g/L. A significant
      amount of D-xylonic acid (ca. 14%) was converted to 3-deoxypentonic acid (3DPA),
      and also, 3,4-dihydroxybutyric acid was formed. 2K3DXA was further converted to
      glycolaldehyde when genes encoding by either YagE or YjhH aldolase from E. coli
      were expressed. Reduction of glycolaldehyde to ethylene glycol by an endogenous
      aldo-keto reductase activity resulted further in accumulation of ethylene glycol
      of 14 mg/L. The possibility of simultaneous production of lactic and glycolic
      acids was evaluated by expression of gene encoding lactate dehydrogenase ldhL
      from Lactobacillus helveticus together with aldA. Interestingly, this increased
      the accumulation of glycolic acid to 1 g/L. The D-xylonate dehydratase activity
      in yeast was notably low, possibly due to inefficient Fe-S cluster synthesis in
      the yeast cytosol, and leading to D-xylonic acid accumulation. The dehydratase
      activity was significantly improved by targeting its expression to mitochondria
      or by altering the Fe-S cluster metabolism of the cells with FRA2 deletion.

PMID- 29038974
TI  - Bioreactors based on immobilized fungi: bioremediation under non-sterile
      conditions.
AB  - White-rot fungi are renowned for their remarkable potential to degrade a wide
      range of organic pollutants. They are applicable in standard bioreactors offering
      both the use of the continuous mode of action and easy upscaling of the
      biodegradation process. The recent advance in this field consisted in the use of
      various fungi and different types of reactors in the treatment of real
      wastewaters. Most degradation studies involving white-rot fungi carried out so
      far used controlled, aseptic conditions. However, during bioremediation of real
      wastewaters, the degradation capacity of the fungi would be significantly
      affected by autochthonous microorganisms. Consequently, for the development of
      sustainable bioremediation technologies, it is important to understand the
      mechanisms involved in the intermicrobial interactions occurring during the
      bioremediation process. This review summarizes recent applications of white-rot
      fungi to biodegradation of recalcitrant organopollutants under non-sterile
      conditions describing the invading microorganism(s) and the way how they affect
      the stability and degradation efficiency of the fungal bioreactor cultures. In
      addition, studies where fungal cultures were exposed to defined microbial stress
      are also reported documenting the effect and mechanisms of microbial
      interactions. Advanced OMICs techniques, specifically the genomics and
      metabolomics analyses, are suggested to help in identification of the invading
      microorganisms and in discovery of mechanisms taking part in the interspecific
      interactions.

PMID- 29038971
TI  - The Implementation of Targeted Temperature Management: An Evidence-Based
      Guideline from the Neurocritical Care Society.
AB  - BACKGROUND: Targeted temperature management (TTM) is often used in neurocritical
      care to minimize secondary neurologic injury and improve outcomes. TTM
      encompasses therapeutic hypothermia, controlled normothermia, and treatment of
      fever. TTM is best supported by evidence from neonatal hypoxic-ischemic
      encephalopathy and out-of-hospital cardiac arrest, although it has also been
      explored in ischemic stroke, traumatic brain injury, and intracranial hemorrhage
      patients. Critical care clinicians using TTM must select appropriate cooling
      techniques, provide a reasonable rate of cooling, manage shivering, and ensure
      adequate patient monitoring among other challenges. METHODS: The Neurocritical
      Care Society recruited experts in neurocritical care, nursing, and
      pharmacotherapy to form a writing Committee in 2015. The group generated a set of
      16 clinical questions relevant to TTM using the PICO format. With the assistance
      of a research librarian, the Committee undertook a comprehensive literature
      search with no back date through November 2016 with additional references up to
      March 2017. RESULTS: The Committee utilized GRADE methodology to adjudicate the
      quality of evidence as high, moderate, low, or very low based on their confidence
      that the estimate of effect approximated the true effect. They generated
      recommendations regarding the implementation of TTM based on this systematic
      review only after considering the quality of evidence, relative risks and
      benefits, patient values and preferences, and resource allocation. CONCLUSION:
      This guideline is intended for neurocritical care clinicians who have chosen to
      use TTM in patient care; it is not meant to provide guidance regarding the
      clinical indications for TTM itself. While there are areas of TTM practice where
      clear evidence guides strong recommendations, many of the recommendations are
      conditional, and must be contextualized to individual patient and system needs.

PMID- 29038975
TI  - Applying a riboregulator as a new chromosomal gene regulation tool for higher
      glycogen production in Synechocystis sp. PCC 6803.
AB  - Cyanobacteria are one of the most attractive hosts for biofuel production;
      however, genetic approaches to regulate specific chromosomal genes in
      cyanobacteria remain limited. With the aim of developing a novel method to
      regulate chromosomal gene expression in cyanobacteria, we focused on
      riboregulatory technology. Riboregulators are composed of two RNA fragments whose
      interaction leads to target gene regulation with high specificity. In this study,
      we inserted a riboregulator sequence upstream of the chromosomal gene encoding
      AbrB-like transcriptional regulator, cyAbrB2, to investigate the utility of this
      tool. The inserted riboregulator was able to regulate cyabrB2 gene expression,
      with a high ON-OFF ratio up to approximately 50-fold. The transcription levels of
      several genes for which cyAbrB2 acts as a transcriptional upregulator were also
      decreased. Further, the cyAbrB2 expression-repressed mutant showed high glycogen
      accumulation, equivalent to that in the cyabrB2 deletion mutant (DeltacyabrB2).
      Phenotypic similarities between the cyabrB2 expression-repressed mutant and the
      DeltacyabrB2 mutant suggest that the riboregulator can potentially be used as a
      new chromosomal gene regulation tool in cyanobacteria.

PMID- 29038976
TI  - Classification of human and zoonotic group hepatitis E virus (HEV) using antigen
      detection.
AB  - Hepatitis E virus (HEV) is one of the major pathogens that cause acute viral
      hepatitis. The human (genotypes 1 and 2) and zoonotic (genotypes 3 and 4) groups
      of HEV present different epidemiology and clinical features. In this study, we
      developed a classification method for rapidly classifying HEV into human or
      zoonotic groups that combines a general antigen test with a zoonotic group
      specific antigen test. Evaluation of serial samples from HEV-infected rhesus
      monkeys indicated that HEV antigen-positive samples can be classified using the
      antigen-based classification method. The antigen-based classification method was
      evaluated further on 55 genotyped samples from acute hepatitis E patients,
      including 9 human and 46 zoonotic groups. The novel method was completely
      consistent with the sequencing results: 9/9 for the human groups (100%, 95%
      confidence interval [CI] 66.4-100%) and 46/46 for the zoonotic groups (100%, 95%
      CI 92.3-100%). This method was also successfully used for the clustering of some
      samples that could not be clustered by sequencing. Compared with the sequencing
      based method, this method is less time-consuming, less expensive, and less
      technically complex and is therefore ideal for large numbers of samples. In
      conclusion, this study provides a convenient and sensitive method for classifying
      different groups of HEV, and it has potentially important public health
      applications, especially in underdeveloped areas that cannot afford the high cost
      of nucleic acid testing.

PMID- 29038978
TI  - Panuveitis-like reaction following encircling laser retinopexy/cerclage in a 21
      year-old male.
AB  - BACKGROUND: Severe vision-impairing ocular inflammation is rarely reported
      following extensive laser. Previous cases have involved retinal photocoagulation
      for diabetic retinopathy resolving over days. This report documents a rare
      instance of this where encircling retinopexy/cerclage was done as fellow eye
      retinal detachment prophylaxis in a patient with no overt comorbidities. RESULTS:
      A panuveitis-like reaction with severe, near-total visual impairment was
      documented 1 day following single-sitting encircling laser retinopexy/cerclage
      done as fellow eye prophylaxis for a 21-year-old male presenting with total
      retinal detachment in the other eye. Pre-laser findings were unremarkable, other
      than an equatorial ring of fine vitreous condensations. Pre-laser vision of 20/20
      uncorrected decreased to hand motion, light perception on all quadrants,
      accompanied by severe anterior segment inflammation with hypopyon, retrolental
      membranes, vitreous cells, and choroidal effusion/suspicious exudative retinal
      detachment on B-scan ultrasound and ultrasound biomicroscopy. Combination of
      oral, topical, and depot steroids resulted in restoration of vision by 1 month
      post-laser, but with persistent anterior segment inflammation and retrolental
      membranes at month 2 post-laser. CONCLUSIONS: The atypically inordinate degree of
      post-laser inflammation and multiple sequelae following encircling
      retinopexy/cerclage as retinal detachment prophylaxis, in this case, demonstrate
      the potency and risks of retinal photocoagulation. The value of pre-laser
      assessment for potential risk factors, caution and mindfulness in conducting the
      intervention, and, the value of prudent and thorough follow-up are exhibited in
      this case.

PMID- 29038977
TI  - Prevalence of Kaposi's sarcoma-associated herpesvirus among intravenous drug
      users: a systematic review and meta-analysis.
AB  - Intravenous drug users (IDUs) have been demonstrated to be highly vulnerable to
      HIV/AIDS. Nevertheless, the prevalence of Kaposi's sarcoma associated herpesvirus
      (KSHV), an important co-infected agent with HIV, among this population remained
      obscure. We conducted a systematic review on the epidemiological features of KSHV
      among IDUs worldwide. Eligible studies were retrieved from 6 electronic databases
      (PubMed, EMBASE, Web of Science, CBM, CNKI and Wanfang). We calculated the pooled
      prevalence and 95% confidence interval (CI) overall and among subgroups using
      either random-effects model or fixed-effects model depending on between-study
      heterogeneity. The potential publication bias was assessed by the Egger's test. A
      meta-regression analysis was performed to explore the sources of heterogeneity.
      Finally, twenty-two studies with a total sample of 7881 IDUs were included in the
      analysis. The pooled prevalence of KSHV was 14.71% (95% CI 11.12%-19.46%) among
      IDUs. Specifically, KSHV prevalence was 10.86% (95% CI 6.95%-16.96%) in HIV
      negative IDUs, and 13.56% (95% CI 10.57%-17.38%) in HIV-positive IDUs. Moreover,
      prevalence among IDUs from the three continents involved in the current study was
      similar: 16.10% (95%CI 7.73%-33.54%) in Asia; 14.22% (95%CI 8.96%-22.57%) in
      Europe and 14.06% (95%CI 11.38%-17.37%) in America. Globally, IDUs are at higher
      risk of the KSHV infection when compared with the general population, regardless
      of geographical region or HIV-infection status.

PMID- 29038979
TI  - Decreased Metabolism in the Posterior Medial Network with Concomitantly Increased
      Metabolism in the Anterior Temporal Network During Transient Global Amnesia.
AB  - Perturbation of corticohippocampal circuits is a key step in the pathogenesis of
      transient global amnesia. We evaluated the spatial distribution of altered
      cerebral metabolism to determine the location of the corticohippocampal circuits
      perturbed during the acute stage of transient global amnesia. A consecutive
      series of 12 patients with transient global amnesia who underwent 18F
      fluorodeoxyglucose positron emission tomography within 3 days after symptom onset
      was identified. We used statistical parametric mapping with two contrasts to
      identify regions of decreased and increased brain metabolism in transient global
      amnesia patients compared with 25 age-matched controls. Transient global amnesia
      patients showed hypometabolic clusters in the left temporal and bilateral parieto
      occipital regions that belong to the posterior medial network as well as,
      hypermetabolic clusters in the bilateral inferior frontal regions that belong to
      the anterior temporal network. The posterior medial and anterior temporal
      networks are the two main corticohippocampal circuits involved in memory-guided
      behavior. Decreased metabolism in the posterior medial network might explain the
      impairment of episodic memory observed during the acute stage of transient global
      amnesia. Concomitant increased metabolism within the anterior temporal network
      might occur as a compensatory mechanism.

PMID- 29038981
TI  - Erratum to: Discussing euthanasia in two German states: scientific terminology
      and public discourse in the German Democratic Republic and the Federal Republic
      of Germany.

PMID- 29038980
TI  - Testing an Incentive-Sensitisation Approach to Understanding Problem Slot-Machine
      Gambling Using an Online Slot-Machine Simulation.
AB  - This study aims to test the application of the incentive-sensitisation theory to
      slot-machine gambling behaviour. The theory posits that for problem gamblers
      (PGs), gambling strengthens the response of motivational pathways in the mid
      brain to gambling cues, eliciting strong wanting, independent of liking. Non
      problem gamblers (NPGs) experience weaker changes to motivational pathways so
      liking and wanting remain associated. Hence, it is predicted that wanting to
      gamble will be greater than liking for PGs but there will be no difference for
      NPGs; wanting will be greater for PGs than for NPGs; and, wanting but not liking
      will predict whether PGs continue gambling, whereas both will predict this for
      NPGs. During gambling on an online simulated slot-machine, 39 PGs and 87 NPGs
      rated 'liking' and 'wanting'. Participants played at least 3 blocks of 10-20
      spins, and then had the option of playing up to 4 additional blocks; to continue
      playing they had to complete an effortful task, so that 'number of blocks played'
      acted as an additional indirect measure of wanting. Results supported hypotheses
      except on the indirect measure of wanting (the number of blocks played).

PMID- 29038982
TI  - Hierarchy, determinism, and specificity in theories of development and evolution.
AB  - The concepts of hierarchical organization, genetic determinism and biological
      specificity (for example of species, biologically relevant macromolecules, or
      genes) have played a crucial role in biology as a modern experimental science
      since its beginnings in the nineteenth century. The idea of genetic information
      (specificity) and genetic determination was at the basis of molecular biology
      that developed in the 1940s with macromolecules, viruses and prokaryotes as major
      objects of research often labelled "reductionist". However, the concepts have
      been marginalized or rejected in some of the research that in the late 1960s
      began to focus additionally on the molecularization of complex biological
      structures and functions using systems approaches. This paper challenges the view
      that 'molecular reductionism' has been successfully replaced by holism and a
      focus on the collective behaviour of cellular entities. It argues instead that
      there are more fertile replacements for molecular 'reductionism', in which
      genomics, embryology, biochemistry, and computer science intertwine and result in
      research that is as exact and causally predictive as earlier molecular biology.

PMID- 29038983
TI  - Refractive, corneal, and ocular residual astigmatism: distribution in a German
      population and age-dependency: the Gutenberg health study.

PMID- 29038984
TI  - Perturbation vectors to evaluate air quality using lichens and bromeliads: a
      Brazilian case study.
AB  - Samples of one lichen species, Parmotrema crinitum, and one bromeliad species,
      Tillandsia usneoides, were collected in the state of Rio de Janeiro, Brazil, at
      four sites differently affected by anthropogenic pollution. The concentrations of
      aluminum, cadmium, copper, iron, lanthanum, lead, sulfur, titanium, zinc, and
      zirconium were determined by inductively coupled plasma-atomic emission
      spectroscopy. The environmental diagnosis was established by examining
      compositional changes via perturbation vectors, an underused family of methods
      designed to circumvent the problem of closure in any compositional dataset. The
      perturbation vectors between the reference site and the other three sites were
      similar for both species, although body concentration levels were different. At
      each site, perturbation vectors between lichens and bromeliads were approximately
      the same, whatever the local pollution level. It should thus be possible to
      combine these organisms, though physiologically different, for air quality
      surveys, after making all results comparable with appropriate correction. The use
      of perturbation vectors seems particularly suitable for assessing pollution level
      by biomonitoring, and for many frequently met situations in environmental
      geochemistry, where elemental ratios are more relevant than absolute
      concentrations.

PMID- 29038985
TI  - Showing the Unsayable: Participatory Visual Approaches and the Constitution of
      'Patient Experience' in Healthcare Quality Improvement.
AB  - This article considers the strengths and potential contributions of participatory
      visual methods for healthcare quality improvement research. It argues that such
      approaches may enable us to expand our understanding of 'patient experience' and
      of its potential for generating new knowledge for health systems. In particular,
      they may open up dimensions of people's engagement with services and treatments
      which exceed both the declarative nature of responses to questionnaires and the
      narrative sequencing of self reports gathered through qualitative interviewing. I
      will suggest that working with such methods may necessitate a more reflexive
      approach to the constitution of evidence in quality improvement work. To this
      end, the article will first consider the emerging rationale for the use of visual
      participatory methods in improvement before outlining the implications of two
      related approaches-photo-elicitation and PhotoVoice-for the constitution of
      'experience'. It will then move to a participatory model for healthcare
      improvement work, Experience Based Co-Design (EBCD). It will argue that EBCD
      exemplifies both the strengths and the limitations of adequating visual
      participatory approaches to quality improvement ends. The article will conclude
      with a critical reflection on a small photographic study, in which the author
      participated, and which sought to harness service user perspectives for the
      design of psychiatric facilities, as a way of considering the potential
      contribution of visual participatory methods for quality improvement.

PMID- 29038986
TI  - Preparation and Evaluation of Artemether Liposomes for Enhanced Anti-Tumor
      Therapy.
AB  - The aim of the study was to design liposomes (Lips) of artemether (ARM), a plant
      derived drug for treatment of metastatic tumors, for the intravenous delivery.
      The ARM-Lips were prepared using ethanol injection method. Based on the
      optimization of formulation with single-factor experiments, ARM-Lips were
      spherical with a uniform particle size (187.3 +/- 1.83) nm and its EE and DL were
      (94.49 +/- 1.18)% and (10.94 +/- 0.10)%, respectively. The in vitro drug release
      characteristics of ARM-Lips possessed a sustained release characteristic, and
      their behavior was in accordance with the first-order kinetics equation. In vivo,
      after intravenous injection to mice, the t1/2beta, MRT, and AUC of ARM-Lips were
      8.38-, 3.38-, and 3.11-fold those of ARM solution (ARM-Sol), respectively. In the
      pharmacodynamics studies, the tumor doubling time, growth inhibition rate, and
      specific growth rate of tumor of ARM-Lips were 1.97 times, 1.54 times, and 0.51
      times those of ARM-Sol, respectively, which indicated that the anti-tumor effect
      of ARM-Lips was significantly stronger than that of ARM-Sol. These encouraging
      results revealed that ARM-Lips would serve as an efficient carrier for ARM for
      increasing therapeutic efficacy on tumor.

PMID- 29038987
TI  - Development and Optimization of a Starch-Based Co-processed Excipient for Direct
      Compression Using Mixture Design.
AB  - The development of novel excipients with enhanced functionality has been explored
      using particle engineering by co-processing. The aim of this study was to improve
      the functionality of tapioca starch (TS) for direct compression by co-processing
      with gelatin (GEL) and colloidal silicon dioxide (CSD) in optimized proportions.
      Design of Experiment (DoE) was employed to optimize the composition of the co
      processed excipient using the desirability function and other supporting studies
      as a basis for selecting the optimized formulation. The co-processed excipient
      (SGS) was thereafter developed by the method of co-fusion. Flow and compaction
      studies of SGS were carried out in comparison to its parent component (TS) and
      physical mixture (SGS-PM). Tablets were prepared by direct compression (DC)
      containing ibuprofen (200 mg) as a model for poor compressibility using SGS,
      Prosolv(r), and StarLac(r) as multifunctional excipients. The optimized
      composition of SGS corresponded to TS (90%), GEL (7.5%), and CSD (2.5%). The
      functionality of SGS was improved relative to SGS-PM in terms of flow and
      compression. Tablets produced with SGS were satisfactory and conformed to USP
      specifications for acceptable tablets. SGS performed better than Prosolv(r) in
      terms of disintegration and was superior to StarLac with respect to tensile
      strength and disintegration time. The application of DoE was successful in
      optimizing and developing a starch-based co-processed excipient that can be
      considered for direct compression tableting.

PMID- 29038988
TI  - Can the gastrointestinal microbiota be modulated by dietary fibre to treat
      obesity?
AB  - Recent research suggests that the human gastrointestinal microbiota is greatly
      involved in yielding, storing and expending energy from the diet; therefore, it
      may be a further factor in linking diet to obesity. The gut microbial composition
      is affected by diet throughout the human lifespan, and is highly dynamic and
      efficient in response to dietary alterations in particular to dietary fibre
      intake. Short-chained fatty acids (SCFA) are the bi-product of fibre fermentation
      and have both obesogenic and anti-obesogenic properties. The production of
      specific forms of SCFAs depends on the microbes available in the gut and the type
      of fibre ingested. The gut microbiome associated with healthy lean individuals
      has a higher microbial biodiversity and a greater Bacteroidete to Firmicute ratio
      compared to the obese individuals associated with microbiome. These gut microbial
      associations are similar to those seen in individuals with high and low dietary
      fibre intakes, respectively. Metabolites generated by Bacteroidetes and
      Firmicutes include the three main SCFA related to obesity, namely butyrate,
      acetate and propionate. However, neither Bacteroidetes nor Firmicutes is purely
      causative or purely preventative of obesity. More research is crucial in linking
      the various types of fibre with particular SCFA production and the microbiome it
      promotes before suggesting that dietary fibre modulation of the gut microbiome
      can treat obesity. However, the long-term dietary trend plays the principal role
      in assembling the diversity and abundance of gut microbes; thus, a sustained diet
      high in fibre may help prevent obesity by promoting a microbiome associated with
      a lean phenotype.

PMID- 29038989
TI  - Interactions Between Carnivores in Madagascar and the Risk of Disease
      Transmission.
AB  - Introduced carnivores exert considerable pressure on native predators through
      predation, competition and disease transmission. Recent research shows that
      exotic carnivores negatively affect the distribution and abundance of the native
      and endangered carnivores of Madagascar. In this study, we provide information
      about the frequency and distribution of interactions between exotic (dogs and
      cats) and native carnivores (Eupleridae) in the Betampona Natural Reserve (BNR),
      Madagascar, using noninvasive camera trap surveys. Domestic dogs (Canis
      familiaris) were the most frequently detected carnivore species within the BNR,
      and we found that indirect interactions between exotic and native carnivores were
      frequent (n = 236). Indirect interactions were more likely to occur near the
      research station (incidence rate ratio = 0.91), which may constitute a disease
      transmission hot spot for carnivores at BNR. The intervals between capture of
      native and exotic carnivores suggest that there is potential for pathogen
      transmission between species in BNR. These capture intervals were significantly
      shorter near the edge of the reserve (P = 0.04). These data could be used to
      implement biosecurity measures to monitor interactions and prevent disease
      transmission between species at the domestic animal and wildlife interface.

PMID- 29038990
TI  - Personality and Alexithymic Disparity in Obsessive-Compulsive Disorder Based on
      Washing and Checking.
AB  - The aim of this study was to investigate pathway relationship of personality
      characteristics and alexithymic traits in OCD symptoms of obsession, and
      compulsive behavior of washing and checking. Two-hundred and seventy patients
      diagnosed with OCD were consecutively recruited from the psychiatric outpatient
      department of a teaching hospital. Structural equation modeling showed those more
      neurotic, less extraverted and with higher levels of alexithymia difficulty
      identifying feelings (DIF), difficulty describing feelings (DDF) and externally
      oriented thinking (EOT) were more likely to develop obsessive thoughts. Those
      less extraverted was more prone to develop washing compulsions, and those more
      neurotic were more likely to develop checking compulsions. EOT was the only
      alexithymic trait to have no gender difference within this group of patients with
      OCDs. The different personality and alexithymic trait pathways found between OCD
      obsession, washing and checking symptoms provide support that they may be
      different subtypes within the OCD diagnosis. Obsession was associated with
      washing, but not checking. Furthermore, no gender difference was found between
      the obsession and compulsive symptoms. Extraversion and neuroticism can be used
      to differentiate washing and checking, and alexithymia to differentiate washing
      and obsessions. This should be taken into consideration for intervention
      targeting patients with different OCD symptoms.

PMID- 29038991
TI  - Pathophysiological and therapeutic implications in patients with atrial
      fibrillation and heart failure.
AB  - Heart failure and atrial fibrillation are common and responsible for significant
      mortality of patients. Both share the same risk factors like hypertension,
      ischemic heart disease, diabetes, obesity, arteriosclerosis, and age. A variety
      of microscopic and macroscopic changes favor the genesis of atrial fibrillation
      in patients with preexisting heart failure, altered subcellular Ca2+ homeostasis
      leading to increased cellular automaticity as well as concomitant fibrosis that
      are induced by pressure/volume overload and altered neurohumoral states. Atrial
      fibrillation itself promotes clinical deterioration of patients with preexisting
      heart failure as atrial contraction significantly contributes to ventricular
      filling. In addition, atrial fibrillation induced tachycardia can even further
      compromise ventricular function by inducing tachycardiomyopathy. Even though
      evidence has been provided that atrial functions significantly and independently
      of confounding ventricular pathologies, correlate with mortality of heart failure
      patients, rate and rhythm controls have been shown to be of equal effectiveness
      in improving mortality. Yet, it also has been shown that cohorts of patients with
      heart failure benefit from a rhythm control concept regarding symptom control and
      hospitalization. To date, amiodarone is the most feasible approach to restore
      sinus rhythm, yet its use is limited by its extensive side-effect profile. In
      addition, other therapies like catheter-based pulmonary vein isolation are of
      increasing importance. A wide range of heart failure-specific therapies are
      available with mixed impact on new onset or perpetuation of atrial fibrillation.
      This review highlights pathophysiological concepts and possible therapeutic
      approaches to treat patients with heart failure at risk for or with atrial
      fibrillation.

PMID- 29038992
TI  - [Soft tissue sarcoma: how can posttreatment alterations be distinguished from
      recurrences?]
AB  - The recognition of recurrent soft tissue sarcomas and the differentiation from
      post-treatment alterations is complex. This article aims to assist the clinical
      radiologist in the systematic evaluation of local follow-up imaging in soft
      tissue sarcoma patients. Soft tissue sarcomas encompass multiple entities with
      different recurrence rates and follow-up intervals. Approved and up to date
      recommendations are provided, including imaging techniques. The past medical
      history of the patient, the clinical situation and previous therapies should be
      known in detail, including surgery, radiation therapy and chemotherapy. Previous
      imaging results should be consulted, if available. This article describes the
      time-dependent imaging spectrum of local post-therapeutic as well as local
      treatment-related complications. These include early complications, such as
      seromas, hematomas and infections, as well as late complications, including
      edema, fibrosis and joint stiffness, and also inflammatory pseudotumors, which
      may occur after variable time intervals. The imaging appearance of local
      recurrent and radiation-associated sarcoma are elucidated. In particular,
      magnetic resonance imaging (MRI) criteria are provided, which may help in
      differentiating post-therapeutic alterations from recurrent soft tissue sarcomas.

PMID- 29038993
TI  - The Ups and Downs of Repeated Cleavage and Internal Fragment Production in Top
      Down Proteomics.
AB  - Analysis of whole proteins by mass spectrometry, or top-down proteomics, has
      several advantages over methods relying on proteolysis. For example, proteoforms
      can be unambiguously identified and examined. However, from a gas-phase ion
      chemistry perspective, proteins are enormous molecules that present novel
      challenges relative to peptide analysis. Herein, the statistics of cleaving the
      peptide backbone multiple times are examined to evaluate the inherent propensity
      for generating internal versus terminal ions. The raw statistics reveal an
      inherent bias favoring production of terminal ions, which holds true regardless
      of protein size. Importantly, even if the full suite of internal ions is
      generated by statistical dissociation, terminal ions are predicted to account for
      at least 50% of the total ion current, regardless of protein size, if there are
      three backbone dissociations or fewer. Top-down analysis should therefore be a
      viable approach for examining proteins of significant size. Comparison of the
      purely statistical analysis with actual top-down data derived from ultraviolet
      photodissociation (UVPD) and higher-energy collisional dissociation (HCD) reveals
      that terminal ions account for much of the total ion current in both experiments.
      Terminal ion production is more favored in UVPD relative to HCD, which is likely
      due to differences in the mechanisms controlling fragmentation. Importantly,
      internal ions are not found to dominate from either the theoretical or
      experimental point of view. Graphical abstract ?.

PMID- 29038994
TI  - Reply to the Comment on: "Nominal Mass?" by Athula B. Attygalle and Julius
      Pavlov, J. Am. Soc. Mass Spectrom. 28, 1737-1738 (2017).

PMID- 29038995
TI  - Characterization and Analysis of Paper Spray Ionization of Organic Compounds.
AB  - Paper spray ionization has arisen relatively recently as a complement and
      alternative to electro- and nanospray ionization with silica capillaries. A
      majority of the work in the present literature focuses on the chemical aspect of
      paper spray. In order to study the physical and phenomenological facet of its
      implementation, we measured current and voltage distributions of Taylor cones. To
      study transport phenomena on filter paper, we addressed the behavior of large,
      sparingly soluble tetraalkylammonium ions, which are usually used as mobility
      standards, in paper spray. The variation of intensity with time of monomers and
      dimers of these ions was measured with a differential mobility analyzer and
      compared with that produced by contamination in the paper. At the same time, we
      evaluated the proficiency of different paper spray techniques for protein
      analysis using nano spray as a reference. Experiments suggest that Taylor cones
      in paper spray are subject to hysteresis, whereas transport phenomena in the
      porous substrate notably affects the ionization of the sample. Additionally, we
      observed that paper spray tends to favor lower charge states in proteins.
      Graphical Abstract.

PMID- 29038996
TI  - Combining Structural Probes in the Gas Phase - Ion Mobility-Resolved Action-FRET.
AB  - In the context of native mass spectrometry, the development of gas-phase
      structural probes sensitive to the different levels of structuration of
      biomolecular assemblies is necessary to push forward conformational studies. In
      this paper, we provide the first example of the combination of ion mobility (IM)
      and Forster resonance energy transfer (FRET) measurements within the same
      experimental setup. The possibility to obtain mass- and mobility-resolved FRET
      measurements is demonstrated on a model peptide and applied to monitor the
      collision-induced unfolding of ubiquitin. Graphical Abstract ?.

PMID- 29038997
TI  - Multiparticle Simulations of Quadrupolar Ion Detection in an Ion Cyclotron
      Resonance Cell with Four Narrow Aperture Detection Electrodes.
AB  - The current paradigm in FT-ICR cell design is to approximate the ideal three
      dimensional quadratic trapping potential as closely as possible to maintain ion
      cloud spatial coherence and achieve long transients, either with hyperbolically
      shaped electrodes, shimming electrodes, or by dynamic harmonization. In sharp
      contrast, the FT-ICR analyzer cell with four narrow aperture detection electrodes
      (NADEL) introduces significant anharmonic terms to the trapping potential. This
      analyzer cell is capable of quadrupolar detection by which one can measure a
      signal that is close to the unperturbed cyclotron frequency. This is far less
      sensitive to trapping potential and space charge shifts than the reduced
      cyclotron frequency measured in conventional ICR cells. The quadrupolar mode of
      ion detection in NADEL cells has been examined previously by SIMION simulations
      of ion clouds with up to 500 ions per simulation. Here, the behavior of the NADEL
      analyzer cell is examined through particle-in-cell (PIC) simulations, which
      allows us to examine the behavior of large populations (tens of thousands) of
      ions with space charge considerations, and to calculate the induced charge on the
      NADEL detection electrodes, and thus the transient signal. PIC simulations
      confirm a unique spatial distribution of the ions, with a coherent motion that
      results in long transient signals. Dependence of the ion cloud and image current
      signal on cell design, ion energy, and magnetron radius are examined. Coalescence
      effects are compared with those found in a dynamically harmonized cell. The
      insensitivity of the measured cyclotron frequency to space-charge is demonstrated
      both with simulations and experimentally. Graphical Abstract ?.

PMID- 29038998
TI  - Effect of Electrode Geometry on the Classification Performance of Rapid
      Evaporative Ionization Mass Spectrometric (REIMS) Bacterial Identification.
AB  - The recently developed automated, high-throughput monopolar REIMS platform is
      suited for the identification of clinically important microorganisms. Although
      already comparable to the previously reported bipolar forceps method,
      optimization of the geometry of monopolar electrodes, at the heart of the system,
      holds the most scope for further improvements to be made. For this, sharp tip and
      round shaped electrodes were optimized to maximize species-level classification
      accuracy. Following optimization of the distance between the sample contact point
      and tube inlet with the sharp tip electrodes, the overall cross-validation
      accuracy improved from 77% to 93% in negative and from 33% to 63% in positive ion
      detection modes, compared with the original 4 mm distance electrode. As an
      alternative geometry, round tube shaped electrodes were developed. Geometry
      optimization of these included hole size, number, and position, which were also
      required to prevent plate pick-up due to vacuum formation. Additional features,
      namely a metal "X"-shaped insert and a pin in the middle were included to
      increase the contact surface with a microbial biomass to maximize aerosol
      production. Following optimization, cross-validation scores showed improvement in
      classification accuracy from 77% to 93% in negative and from 33% to 91% in
      positive ion detection modes. Supervised models were also built, and after the
      leave 20% out cross-validation, the overall classification accuracy was 98.5% in
      negative and 99% in positive ion detection modes. This suggests that the new
      generation of monopolar REIMS electrodes could provide substantially improved
      species level identification accuracies in both polarity detection modes.
      Graphical abstract.

PMID- 29038999
TI  - Methods for Cytogenetic Chromosome Barcoding and Chromosome Painting in
      Brachypodium distachyon and Its Relative Species.
AB  - Brachypodium distachyon provides a particularly appealing object for molecular
      cytogenetic analysis due to its compact genome and low repetitive DNA content, as
      well as low (x = 5) basic number of chromosomes easily identifiable on the basis
      of their morphometric features. Some of these features, such as genome
      compactness, are shared by the other members of the genus, thus making them
      amenable for comparative cytogenetic mapping. Cytogenetic infrastructure
      established for B. distachyon was initially based on fluorescence in situ
      hybridization with various tandemly repeated sequences as probes. The molecular
      cytogenetic studies advanced greatly with the development of B. distachyon large
      DNA insert genomic libraries. These resources coupled with the access to the
      fully sequenced genome of B. distachyon enabled chromosome painting in monocots
      for the first time. This pioneering work was subsequently extended to other
      Brachypodium species, allowing insight into grass karyotype evolution. In this
      protocol we describe the methods of making somatic and meiotic chromosome
      preparations, probe labeling, FISH with BAC clones, a strategy for chromosome
      barcoding and chromosome painting in B. distachyon, and comparative chromosome
      painting in the other Brachypodium species.

PMID- 29039000
TI  - Transcriptional and Posttranscriptional Regulation of Drought Stress Treatments
      in Brachypodium Leaves.
AB  - Plant sensing drought stress conditions activate complex molecular networks
      leading to a rapid reprogramming of plant physiology and metabolism, in order to
      survive in suboptimal conditions.Here, we describe a standardized in vivo soil
      drought assay to investigate the effects of drought stress on leaf growth. Since
      it is now clear that stress responses can be specific to developmental stages and
      cell types, we describe a procedure to dissect the leaf in three distinct areas
      in order to study transcriptional and posttranscriptional gene regulation on both
      organ and cellular levels. Noncoding RNAs, both small RNAs and long noncoding
      RNAs, are emerging to be deeply involved in abiotic stress responses, acting as
      molecular switches, interconnecting different response pathways. Here, we
      illustrate the methodology that has been used to identify miRNAs involved in
      drought response and to analyze the modulation of expression of their putative
      targets, in order to gain a complete picture of transcriptional and
      posttranscriptional regulation driven by noncoding RNAs.

PMID- 29039001
TI  - Brachypodium distachyon Long Noncoding RNAs: Genome-Wide Identification and
      Expression Analysis.
AB  - Recent advances in high throughput sequencing technology have revealed a
      pervasive and complex transcriptional activity of all eukaryotic genomes and have
      allowed the identification and characterization of several classes of noncoding
      RNAs (ncRNAs) with key roles in various biological processes. Among ncRNAs, long
      ncRNAs (lncRNAs) are transcripts typically longer than 200 nucleotides whose
      members tend to be expressed at low levels, show a lack of phylogenetic
      conservation and exhibit tissue-specific, cell-specific, or stress-responsive
      expression profiles.Although a large set of lncRNAs has been identified both in
      animal and plant systems, the regulatory roles of lncRNAs are only beginning to
      be recognized and the molecular basis of lncRNA mediated gene regulation remains
      largely unexplored, particularly in plants.Here, we describe an efficient
      methodology to identify long noncoding RNAs using next-generation sequencing
      data.

PMID- 29039002
TI  - A Highly Efficient and Reproducible Fusarium spp. Inoculation Method for
      Brachypodium distachyon.
AB  - Fusarium spp. are devastating fungal pathogens which cause significant losses in
      many cereal crops like wheat, maize, and barley. Genetic improvement of disease
      resistance requires an improved understanding of defense-associated processes
      operating in the host in response to an attack by Fusarium spp. Brachypodium
      distachyon is emerging as a model where host-cereal-infecting pathogen
      interactions can be studied conveniently. However, this requires developing an
      efficient infection assay that facilitates quick screening of germplasm (e.g.,
      mutant lines). Here, we provide an efficient and reproducible Fusarium infection
      assay for Brachypodium. We believe this method will help further develop
      Brachypodium as a model for genetic improvement of disease resistance in cereals
      against Fusarium pathogens.

PMID- 29039003
TI  - Tissue Culture (Somatic Embryogenesis)-Induced Tnt1 Retrotransposon-Based
      Mutagenesis in Brachypodium distachyon.
AB  - Brachypodium distachyon is a model grass species for economically important
      cereal crops. Efforts are in progress to develop useful functional genomic
      resources in Brachypodium. A tobacco retrotransposon, Tnt1, has been used
      successfully in recent past to generate insertional mutagenesis in several dicot
      plant species. Tnt1 retrotransposon replicates, transposes, and inserts at
      multiple random genomic locations in the plant genome. Transposition occurs only
      during somatic embryogenesis but not during seed transmission. We developed
      Brachypodium transgenic plants that can express the Tnt1 element. Here, we
      describe an efficient tissue culture-based approach to generate Tnt1 insertional
      mutant population using transgenic Brachypodium line expressing the Tnt1
      retrotransposon.

PMID- 29039004
TI  - Methods for Xyloglucan Structure Analysis in Brachypodium distachyon.
AB  - Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) has become an important tool for the analysis of biomolecules,
      such as DNA, peptides, and oligosaccharides. This technique has been developed as
      a rapid, sensitive, and accurate means for analyzing cell wall polysaccharide
      structures. Here, we describe a method using mass spectrometry to provide
      xyloglucan composition and structure information of Brachypodium plants which
      will be useful for functional characterization of xyloglucan biosynthesis pathway
      in Brachypodium distachyon.

PMID- 29039005
TI  - Genomic Approaches to Analyze Alternative Splicing, A Key Regulator of
      Transcriptome and Proteome Diversity in Brachypodium distachyon.
AB  - Alternative splicing (AS) promotes transcriptome and proteome diversity in
      plants, which influences growth and development, and host responses to stress.
      Advancements in next-generation sequencing, bioinformatics, and computational
      biology tools have allowed biologists to investigate AS landscapes on a genome
      wide scale in several plant species. Furthermore, the development of Brachypodium
      distachyon (Brachypodium) as a model system for grasses has facilitated
      comparative studies of AS within the Poaceae. These analyses revealed a plethora
      of genes in several biological processes that are alternatively spliced and
      identified conserved AS patterns among monocot and dicot plants. In this chapter,
      using a Brachypodium-virus pathosystem as a research template, we provide an
      overview of genomic and bioinformatic tools that can be used to investigate
      constitutive and alternative splicing in plants.

PMID- 29039006
TI  - Information Resources for Functional Genomics Studies in Brachypodium distachyon.
AB  - Online tools and databases play an essential role in the promotion of functional
      genomics studies. Several resources for information regarding Brachypodium
      distachyon (Brachypodium) are available on the Web. In this chapter, we focus on
      recently published resources for Brachypodium research. The Brachypodium.org
      website ( http://www.brachypodium.org /) is an information portal that provides
      links to various genomic resources regarding Brachypodium, including genome
      annotation and re-sequencing datasets of accessions. RIKEN Full-length cDNA
      Database (RBFLDB, http://brachy.bmep.riken.jp/ver.1/index.pl ) is a web
      accessible database that provides information of Brachypodium full-length cDNAs
      (FLcDNAs) collected in RIKEN and updated gene structures of Brachypodium based on
      the FLcDNA sequences as well as results of comparative analyses with available
      sequence resources for Triticeae crops, wheat, and barley. We introduce the
      functionalities and availability of these important information resources.
      Furthermore, we also present brief descriptions of useful online tools that
      facilitate Brachypodium functional genomics studies.

PMID- 29039007
TI  - Methods for Functional Transgenics: Development of Highly Efficient
      Transformation Protocol in Brachypodium and Its Suitability for Advancing
      Brachypodium Transgenics.
AB  - Plant transformation is an invaluable technique in plant genomics by which an
      extra foreign DNA sequence is introduced into a plant genome. Changing the plant
      genome is leading to owning new genetic characteristics. Model plant is a
      keystone in a study of the comprehensive plant phylum. Here, I describe an
      efficient method to transform the plant species Brachypodium distachyon which,
      due to its characters, is developing to be an important plant model.

PMID- 29039008
TI  - Molecular Markers in Whole Genome Evolution of Brachypodium.
AB  - Molecular markers play more and more important role in population genetic and
      phylogenetic studies; choice of marker systems for a particular study has become
      a serious problem. These marker systems have different advantages and
      disadvantages, so it is imperative to keep in mind all the pros and cons of the
      technique while selecting one for the problem to be addressed.Here, we concisely
      introduced three molecular marker techniques, namely SSR, ISSR, and RFLP. We
      elaborated their properties such as reliability, simplicity, cost-effectiveness,
      and speed, in addition to data analysis of genetic diversity. We have outlined
      here the whole methodology of these techniques.

PMID- 29039009
TI  - Estimate Codon Usage Bias Using Codon Usage Analyzer (CUA).
AB  - One amino acid is added to a growing peptide by a ribosome through reading triple
      nucleotides, i.e., a codon, each time. Twenty species of amino acids are often
      coded by 61 codons, so one amino acid can be coded by more than one codon and the
      codons coding the same amino acid are called synonymous. Intriguingly, synonymous
      codons' usage is often uneven: some are used more often than their alternatives
      in a genome. The unevenness of codon usage is termed codon usage bias (CUB). CUB
      is widespread, and its causes and consequences have been under intensive
      investigation. To facilitate the studying of CUB, in this chapter we present a
      protocol of estimating CUB by using the free software Codon Usage Analyzer, and
      apply it to Brachypodium distachyon as an example. To accomplish this protocol,
      the readers need some basic command-line skills. Briefly, the protocol comprises
      four major steps: downloading data and software, setting up computing
      environment, preparing data, and estimating CUB.

PMID- 29039010
TI  - Identification of Pseudogenes in Brachypodium distachyon Chromosomes.
AB  - Pseudogenes are gene copies that have lost the capability to encode a functional
      protein. Based on their structure, pseudogenes are classified in two types.
      Processed pseudogenes arise by a process of retrotranscription from a spliced
      mRNA and subsequent integration into the genome. Nonprocessed (or duplicated)
      pseudogenes are generated by genomic duplication and subsequent mutations that
      disable their functionality so that they cannot longer encode a functional
      protein. Differently from processed pseudogenes, duplicated pseudogenes are
      expected to conserve the exon-intron structure of their functional paralogs.Here,
      we describe a computational pipeline for identifying pseudogenes of both types in
      B. distachyon chromosomes. Our pipeline (1) identifies pseudogenes based on
      tBLASTn searches of B. distachyon proteins against the noncoding genomic
      complement of the same species, (2) identifies the most homologous pseudogenes
      functionally paralogous as the pseudogene paternal locus, (3) uses the intron
      exon structure of paternal genes to distinguish between pseudogene types.The
      pipeline is presented in its composing steps and tested on the Brachypodium
      distachyon Bd1 scaffold.

PMID- 29039011
TI  - TILLING in Brachypodium distachyon.
AB  - TILLING is a low-cost screening method that allows for identification of
      mutations in a gene-of-interest within a range of few base pairs. TILLING can be
      applied to mutant populations or to plant collections of cultivars, landraces or
      crop wild relatives (Eco-TILLING). The method is based on the Cel1 enzyme
      cleavage of mismatches in PCR products amplified with labeled primers. The
      cleavage can be detected due to the labeled primers by different methods
      including capillary electrophoresis. Here, we introduce the development of the
      mutant population BRACHYLIFE and present a Brachypodium TILLING protocol based on
      fluorescing primers for PCR, enzymatic cleavage, and detection with Applied
      Biosystems 3130xl Genetic Analyzer.

PMID- 29039012
TI  - Method for the Large-Scale Identification of phasiRNAs in Brachypodium
      distachyon.
AB  - Postranscriptional regulation has been widely shown to be regulated by several
      classes of small non-coding RNAs; most abundantly, microRNAs, which have been
      shown to be the first dominant class and has been widely characterized as post
      transcriptional regulators. In addition to microRNAs, triggered by miRNAs,
      transcripts called as PHAS (or TAS) generate abundant class of small RNAs in 21
      nt manner, which is a pattern formed by DICER-LIKE 4 (DCL4) processing. Although
      PHAS can be identified by aligning transcripts to reported PHAS in other species,
      the most sensitive and accurate way to discovery them is by mapping of the
      smallRNAs taking into account the transcript coordinates. Here, we describe a
      workflow that can be used for the identification PHAS and corresponding phasiRNAs
      in Brachypodium distachyon using publically availabe smallRNAs datasets.

PMID- 29039013
TI  - Evaluation of Genome-Wide Markers and Orthologous Markers in Brachypodium
      distachyon.
AB  - Molecular markers play an important role in identifying the species variation,
      characterizing the genic diversity, and also linking the identified markers to
      trait of interest. Genome- and transcriptome-derived molecular markers have been
      widely used to understand the geographical diversity and have also played a major
      role in the development of high-density linkage maps. In the present protocol, we
      present a detailed protocol on bioinformatics approaches towards the whole-genome
      and transcriptome-assisted simple sequence repeats (SSRs) marker mining in
      Brachypodium distachyon and identification of orthologus SSRs and their
      validation in Brachypodium ecotypes. We also present a protocol for the
      validation of the identified markers.

PMID- 29039014
TI  - Protocol for Coexpression Network Construction and Stress-Responsive Expression
      Analysis in Brachypodium.
AB  - Identifying functionally coexpressed genes and modules has increasingly become
      important to understand the transcriptional flux and to understand large scale
      gene association. Application of the graph theory and combination of tools has
      allowed to understand the genic interaction and to understand the role of hub and
      non-hub proteins in plant development and its ability to cope with stress.
      Association genetics has also been coupled with network modules to map these key
      genes as e-QTLs. High throughput sequencing approaches has revolutionized the
      mining of the gene behavior and also the association of the genes over time
      series. The present protocol chapter presents a unified workflow to understand
      the transcriptional modules in Brachypodium distachyon using weighted coexpressed
      gene network analysis approach.

PMID- 29039015
TI  - Whole Genome DNA Methylation Analysis Using Next-Generation Sequencing (BS-seq).
AB  - Plant methylation is widely evident and has played crucial roles ranging in
      defining the epi-genome variations during abiotic and biotic stress. Variations
      in epi-genomic level has observed not only in the symmetrical as well as the non
      symmetrical sequences. Plethora of these epi-genomic variations have been widely
      also demonstrated at the flowering, tissue-specific, and also at developmental
      stages revealing a strong association of the observed epi-alleles to the
      physiological state. In the present chapter, epi-genomic analysis of the s has
      been described with functional workflow and illustrated methodology.

PMID- 29039016
TI  - Application of Tissue Culture and Transformation Techniques in Model Species
      Brachypodium distachyon.
AB  - Brachypodium distachyon has recently emerged as a model plant species for the
      grass family (Poaceae) that includes major cereal crops and forage grasses. One
      of the important traits of a model species is its capacity to be transformed and
      ease of growing both in tissue culture and in greenhouse conditions. Hence, plant
      transformation technology is crucial for improvements in agricultural studies,
      both for the study of new genes and in the production of new transgenic plant
      species. In this chapter, we review an efficient tissue culture and two different
      transformation systems for Brachypodium using most commonly preferred gene
      transfer techniques in plant species, microprojectile bombardment method
      (biolistics) and Agrobacterium-mediated transformation.In plant transformation
      studies, frequently used explant materials are immature embryos due to their
      higher transformation efficiencies and regeneration capacity. However, mature
      embryos are available throughout the year in contrast to immature embryos. We
      explain a tissue culture protocol for Brachypodium using mature embryos with the
      selected inbred lines from our collection. Embryogenic calluses obtained from
      mature embryos are used to transform Brachypodium with both plant transformation
      techniques that are revised according to previously studied protocols applied in
      the grasses, such as applying vacuum infiltration, different wounding effects,
      modification in inoculation and cocultivation steps or optimization of
      bombardment parameters.

PMID- 29039017
TI  - Cerebral venous sinus thrombosis complicated by seizures: a retrospective
      analysis of 69 cases.
AB  - Cerebral venous sinus thrombosis (CVST) is a rare ischemic cerebrovascular
      disease. The aim of this retrospective observational study was to investigate the
      risk factors for complication of cerebral venous sinus thrombosis by seizures and
      to explore the impact of such seizures on clinical outcomes. Patients with
      cerebral venous sinus thrombosis with or without epileptic seizures were
      retrospectively analyzed and compared in terms of clinical variables, causative
      factors, clinical presentation, and imaging data. In all, 69 patients with
      cerebral venous sinus thrombosis were enrolled in this study, 32 (46.38%) of whom
      had experienced secondary seizures. Compared with those with no seizures,
      significantly more patients with secondary seizures had hemiplegia (37.50 vs.
      15.63%; P = 0.020), bleeding (29.40 vs. 10.81%; P = 0.047), lesions involving the
      frontal (31.25 vs. 10.81%; P = 0.023) and temporal lobe (43.75 vs. 8.11%; P =
      0.005), and thrombosis in the superior sagittal sinus (65.63 vs. 40.54%; P =
      0.036). Multivariate logistic regression analysis showed focal neurological
      deficits (P = 0.004, odds ratio = 5.16, 95% CI 1.99-15.76) and thrombosis of the
      superior sagittal sinus (P = 0.039, odds ratio = 0.13, 95% CI 0.04-0.37) were
      independent risk factors for secondary seizures in patients with cerebral venous
      sinus thrombosis. In addition, mortality rate (9.38 vs. 5.41%; P = 0.469) and 90
      day excellent prognosis rate (81.25 vs. 86.47%; P = 0.793) did not differ
      significantly between patients with and without epileptic seizures. The presence
      of focal neurological deficits and thrombosis of the superior sagittal sinus are
      independent risk factors for secondary seizures in patients with cerebral venous
      sinus thrombosis, whereas mortality and 90-day prognosis have no correlation with
      secondary seizures.

PMID- 29039019
TI  - A successful treatment for a lesion of chronic total occlusion using guiding
      catheter lock technique.

PMID- 29039018
TI  - The Activity Demands and Physiological Responses Encountered During Basketball
      Match-Play: A Systematic Review.
AB  - BACKGROUND: Basketball is a popular, court-based team sport that has been
      extensively studied over the last decade. OBJECTIVE: The purpose of this article
      was to provide a systematic review regarding the activity demands and
      physiological responses experienced during basketball match-play according to
      playing period, playing position, playing level, geographical location, and sex.
      METHODS: An electronic database search of relevant articles published prior to 30
      September 2016 was performed with PubMed, MEDLINE, ERIC, Google Scholar, SCIndex,
      and ScienceDirect. Studies that measured activity demands and/or physiological
      responses during basketball match-play were included. RESULTS: Following
      screening, 25 articles remained for review. During live playing time across 40
      min matches, male and female basketball players travel 5-6 km at average
      physiological intensities above lactate threshold and 85% of maximal heart rate
      (HR). Temporal comparisons show a reduction in vigorous activities in the fourth
      quarter, likely contributing to lower blood lactate concentrations and HR
      responses evident towards the end of matches. Guards tend to perform a higher
      percentage of live playing time sprinting and performing high-intensity shuffling
      compared with forwards and centers. Guards also perform less standing and walking
      during match-play compared with forwards and centers. Variations in activity
      demands likely account for the higher blood lactate concentrations and HR
      responses observed for guards compared with forwards and centers. Furthermore,
      higher-level players perform a greater intermittent workload than lower-level
      players. Moreover, geographical differences may exist in the activity demands
      (distance and frequency) and physiological responses between Australian, African,
      and European basketball players, whereby Australian players sustain greater
      workloads. While activity demands and physiological data vary across playing
      positions, playing levels, and geographical locations, male and female players
      competing at the same level experience similar demands. CONCLUSION: The current
      results provide a detailed description of the specific requirements placed on
      basketball players during match-play according to playing period, playing level,
      playing position, geographical location, and sex, which may be useful in the
      development of individualized basketball training drills.

PMID- 29039020
TI  - Systemic Inflammation and Multimodal Biomarkers in Amnestic Mild Cognitive
      Impairment and Alzheimer's Disease.
AB  - There is increasing evidence suggesting that one of the most relevant
      pathophysiological features of Alzheimer's disease (AD) is neuroinflammation,
      which plays an important role in the production and regulation of AD-related
      proteins (amyloid beta (Abeta) and Tau) and exacerbates AD pathology.
      Neuroinflammation can also be induced by systemic influences (factors from
      outside the central nervous system). However, the role of systemic inflammation
      in AD pathophysiology is much less understood. Thus, our main objective in this
      study was to verify whether the presence of serum cytokines (IL-1beta, IL-6, IL
      10, IL-12, and TNF-alpha) affects different AD biomarkers: Abeta1-42 and Tau
      protein levels, hippocampal volumes (HV), and default mode network functional
      connectivity (DMN FC) in healthy elderly controls, amnestic mild cognitive
      impairment (aMCI) patients due to AD, and mild AD patients. To accomplish this,
      we acquired 3-T MRI, blood, and cerebrospinal fluid (CSF) samples from 42 healthy
      controls, 55 aMCI patients due to AD, and 33 mild AD patients. Comparing the
      groups, we found that the mild AD patients presented smaller HV, disrupted DMN
      FC, and proportionally less IL-1beta than the controls. The aMCI patients only
      differed from the controls in DMN FC. In intra-group comparison, aMCI and mild AD
      with detectable levels of cytokines (TNF-alpha, IL-1beta, IL-10, and IL-12) had
      decreased DMN FC. On the other hand, patients with detectable levels of IL-10 and
      IL-12 presented a more favorable AD biomarkers profile (larger HV, more CSF
      Abeta1-42, and less p-Tau), indicating a possible protective role of these ILs.
      Our findings indicate a possible relationship between systemic inflammation with
      DMN FC disruption, hippocampal atrophy, and CSF protein levels in the subjects
      with mild AD and aMCI.

PMID- 29039021
TI  - Fifty-Hertz Magnetic Field Affects the Epigenetic Modulation of the miR-34b/c in
      Neuronal Cells.
AB  - The exposure to extremely low-frequency magnetic fields (ELF-MFs) has been
      associated to increased risk of neurodegenerative diseases, although the
      underlying molecular mechanisms are still undefined. Since epigenetic modulation
      has been recently encountered among the key events leading to neuronal
      degeneration, we here aimed at assessing if the control of gene expression
      mediated by miRNAs, namely miRs-34, has any roles in driving neuronal cell
      response to 50-Hz (1 mT) magnetic field in vitro. We demonstrate that ELF-MFs
      drive an early reduction of the expression level of miR-34b and miR-34c in SH
      SY5Y human neuroblastoma cells, as well as in mouse primary cortical neurons, by
      affecting the transcription of the common pri-miR-34. This modulation is not p53
      dependent, but attributable to the hyper-methylation of the CpG island mapping
      within the miR-34b/c promoter. Incubation with N-acetyl-l-cysteine or glutathione
      ethyl-ester fails to restore miR-34b/c expression, suggesting that miRs-34 are
      not responsive to ELF-MF-induced oxidative stress. By contrast, we show that miRs
      34 control reactive oxygen species production and affect mitochondrial oxidative
      stress triggered by ELF-MFs, likely by modulating mitochondria-related miR-34
      targets identified by in silico analysis. We finally demonstrate that ELF-MFs
      alter the expression of the alpha-synuclein, which is specifically stimulated
      upon ELF-MFs exposure via both direct miR-34 targeting and oxidative stress.
      Altogether, our data highlight the potential of the ELF-MFs to tune redox
      homeostasis and epigenetic control of gene expression in vitro and shed light on
      the possible mechanism(s) producing detrimental effects and predisposing neurons
      to degeneration.

PMID- 29039022
TI  - Metformin Inhibits the Development of L-DOPA-Induced Dyskinesia in a Murine Model
      of Parkinson's Disease.
AB  - Metformin is a medication that is widely prescribed for the management of type 2
      diabetes. In addition to its anti-diabetic uses, metformin has been proposed as a
      therapeutically effective drug candidate in various central nervous system
      disorders, including Parkinson's disease (PD). PD is characterized by severe
      movement defects and is commonly treated with the dopamine (DA) precursor 3,4
      dihydroxyphenyl-l-alanine (L-DOPA). However, prolonged use of L-DOPA can lead to
      the development of L-DOPA-induced dyskinesia (LID). Here, we hypothesized that
      metformin co-treatment would improve LID in the 6-hydroxydopamine (6-OHDA)
      lesioned mouse model of PD. Metformin did not interfere the pharmacotherapeutic
      effects of L-DOPA in the cylinder test. Furthermore, metformin co-treatment with
      L-DOPA attenuated the development of LID in unilaterally 6-OHDA-lesioned mice.
      Metformin showed a long-lasting effect on axial, limb, and orofacial abnormal
      involuntary movement scores for up to 20 days after treatment initiation.
      Interestingly, persistent enhancement of the mammalian target of rapamycin,
      dopamine D1 receptor, and extracellular signaling-regulated kinase 1/2 signaling
      was maintained in the DA-denervated striatum during metformin treatment.
      Metformin globally normalized the increased glycogen synthase kinase 3beta
      activity induced by chronic treatment of L-DOPA in a manner associated with Akt
      activation in unilaterally 6-OHDA-lesioned mice. These findings suggest that
      metformin may have therapeutic potential for the suppression or management of L
      DOPA-induced motor complications in patients with PD.

PMID- 29039024
TI  - Comment on "Clinical and Psychosocial Outcomes of Vascularized Lymph Node
      Transfer for the Treatment of Upper Extremity Lymphedema After Breast Cancer
      Therapy".

PMID- 29039023
TI  - Astaxanthin Ameliorates Doxorubicin-Induced Cognitive Impairment (Chemobrain) in
      Experimental Rat Model: Impact on Oxidative, Inflammatory, and Apoptotic
      Machineries.
AB  - Chemobrain refers to a common sequelae experienced by 15-80% of cancer patients
      exposed to chemotherapeutics. The antineoplastic agent doxorubicin (DOX) has been
      implicated in a strenuous neurotoxicity manifested as decline in cognitive
      functions, most probably via cytokine-induced oxidative and nitrosative damage to
      brain tissues. Astaxanthin (AST), a naturally occurring carotenoid, is reputable
      for its outstanding antioxidant, anti-inflammatory, and antiapoptotic activities.
      Therefore, the aim of the current study was to investigate the potential
      neuroprotective and memory-enhancing effects of AST against DOX-induced
      behavioral and neurobiological abnormalities. Briefly, AST treatment (25 mg/kg)
      significantly protected against DOX-induced memory impairment. Furthermore, AST
      restored hippocampal histopathological architecture, halted DOX-induced oxidative
      and inflammatory insults, mitigated the increase in acetylcholinesterase
      activity, and consistently downregulated the overactive apoptotic machineries. In
      conclusion, these findings suggest that AST offers neuroprotection against DOX
      induced cognitive impairment which could be explained at least partly by its
      antioxidant, anti-inflammatory, and antiapoptotic effects.

PMID- 29039025
TI  - Cost-effectiveness Analysis of Contralateral Prophylactic Mastectomy Compared to
      Unilateral Mastectomy with Routine Surveillance for Unilateral, Sporadic Breast
      Cancer.
AB  - BACKGROUND: Contralateral prophylactic mastectomy (CPM) rates in younger women
      with unilateral breast cancer have more than doubled. Studies of cost and quality
      of life of the procedure remain inconclusive. METHODS: A cost-effectiveness
      analysis using a decision-tree model in TreeAge Pro 2015 was used to compare long
      term costs and quality of life following unilateral mastectomy (UM) with routine
      surveillance versus CPM for sporadic breast cancer in women aged 45 years. A 10
      year risk period for contralateral breast cancer (CBC), reconstruction, wound
      complications, cost of routine surveillance, and treatment for CBC were used to
      estimate accrued costs. In addition, a societal perspective was used to estimate
      quality-adjusted life years (QALYs) following either treatment for a period of 30
      years. Medical costs were obtained from the 2014 Medicare physician fee schedule
      and event probabilities were taken from recent literature. RESULTS: The mean cost
      of UM with surveillance was $14,141 and CPM was $20,319. Treatment with CPM
      resulted in $6178 more in costs but equivalent QALYs (17.93) compared with UM
      over 30 years of follow-up. Even with worst-case scenario and varying
      assumptions, CPM is dominated by UM in terms of cost and quality. CONCLUSIONS:
      From this refined model, UM with routine surveillance costs less and provides an
      equivalent quality of life. Patients undergoing CPM may eliminate the anxiety of
      routine surveillance, but they face the burden of higher lifetime medical costs.

PMID- 29039026
TI  - Comments to "Long-Term Survival Benefit and Potential for Cure After R1 Resection
      for Colorectal Liver Metastases".

PMID- 29039027
TI  - Reply to "Analysis of 340 Patients with Solid Pseudopapillary Tumors of the
      Pancreas: A Closer Look at Patients with Metastatic Disease; Methodologic
      Issues," by Safiri, Saeid et al.

PMID- 29039028
TI  - Prognostic Value of Computed Tomography: Measured Parameters of Body Composition
      in Primary Operable Gastrointestinal Cancers: Methodologic Issues.

PMID- 29039029
TI  - Analysis of 340 Patients with Solid Pseudopapillary Tumors of the Pancreas: A
      Closer Look at Patients with Metastatic Disease: Methodological Issues.

PMID- 29039030
TI  - Size and Location are the Most Important Risk Factors for Malignant Behavior in
      Resected Solitary Fibrous Tumors.
AB  - PURPOSE: While previously thought to be clinically indolent, recent data suggest
      significant late metastatic capacity of solitary fibrous tumors (SFTs). We define
      prognostic factors for recurrence and disease-specific death (DSD) in resected
      primary SFTs. METHODS: Resected primary SFTs from 1982 to 2015 were identified
      from a prospective, single institutional database. Risk factors for local (LR)
      and distant recurrence (DR), and DSD were assessed using competing risk analysis.
      RESULTS: A total of 219 patients with median follow-up of 6.1 (0.1-22) years were
      included. Five- and 10-year cumulative DSD was 9 and 11%, respectively. Size
      greater than the median 8 cm, gender, location, and complete gross resection were
      significantly associated with DSD (p < 0.05). Five- and 10-year cumulative risk
      (CR) of LR was 4 and 7%, whereas 5- and 10-year CR of DR was 13 and 16%,
      respectively. LR was associated with location (p = 0.02) and tumor size (p =
      0.02), and DR was associated with size (p < 0.01). Histopathologic classification
      did not predict long-term behavior with both malignant and benign tumors
      demonstrating capacity for DR and associated death. Tumors in the thoracic cavity
      and abdomen/retroperitoneum presented the greatest risk of DR (16 and 27% 10-year
      CR). On multivariate analysis, size >= 8 cm (hazard ratio 2.89, p = 0.05) and
      tumor location in chest or abdominal/retroperitoneal cavity (hazard ratio 2.68, p
      = 0.01) significantly impacted DSD. CONCLUSIONS: Recurrence is highly associated
      with DSD and events occur as late as 16 years after initial presentation,
      including in patients with initially considered benign tumors. Patients with
      large (>= 8 cm) tumors in the chest or abdominal/retroperitoneal cavity are at
      greatest risk.

PMID- 29039031
TI  - Developmental push or environmental pull? The causes of macroevolutionary
      dynamics.
AB  - Have the large-scale evolutionary patterns illustrated by the fossil record been
      driven by fluctuations in environmental opportunity, by biotic factors, or by
      changes in the types of phenotypic variants available for evolutionary change?
      Since the Modern Synthesis most evolutionary biologists have maintained that
      microevolutionary processes carrying on over sufficient time will generate
      macroevolutionary patterns, with no need for other pattern-generating mechanisms
      such as punctuated equilibrium or species selection. This view was challenged by
      paleontologists in the 1970s with proposals that the differential sorting and
      selection of species and clades, and the effects of biotic crises such as mass
      extinctions, were important extensions to traditional evolutionary theory. More
      recently those interested in macroevolution have debated the relative importance
      of abiotic and biotic factors in driving macroevolutionary patterns and have
      introduced comparative phylogenetic methods to analyze the rates of change in
      taxonomic diversity. Applying Peter Godfrey-Smith's distinction between
      distributional explanations and explanations focusing on the origin of variation,
      most macroevolutionary studies have provided distributional explanations of
      macroevolutionary patterns. Comparative studies of developmental evolution,
      however, have implicated the origin of variants as a driving macroevolution
      force. In particular, the repatterning of gene regulatory networks provides new
      insights into the origins of developmental novelties. This raises the question of
      whether macroevolution has been pulled by the generation of environmental
      opportunity, or pushed by the introduction of new morphologies. The contrast
      between distributional and origination scenarios has implications for
      understanding evolutionary novelty and innovation and how macroevolutionary
      process may have evolved over time.

PMID- 29039032
TI  - CD146 is essential for PDGFRbeta-induced pericyte recruitment.

PMID- 29039033
TI  - Protein crystal quality oriented disulfide bond engineering.

PMID- 29039034
TI  - Inactivation of NSF ATPase Leads to Cathepsin B Release After Transient Cerebral
      Ischemia.
AB  - Neurons have extraordinary large cell membrane surface area, thus requiring
      extremely high levels of intracellular membrane-trafficking activities.
      Consequently, defects in the membrane-trafficking activities preferentially
      affect neurons. A critical molecule for controlling the membrane-trafficking
      activities is the N-ethylmaleimide-sensitive factor (NSF) ATPase. This study is
      to investigate the cascade of events of NSF ATPase inactivation, resulting in a
      massive buildup of late endosomes (LEs) and fatal release of cathepsin B (CTSB)
      after transient cerebral ischemia using the 2-vessel occlusion with hypotension
      (2VO+Hypotension) global brain ischemia model. Rats were subjected to 20 min of
      transient cerebral ischemia followed by 0.5, 4, 24, and 72 h of reperfusion.
      Neuronal histopathology and ultrastructure were examined by the light and
      electron microscopy, respectively. Western blotting and confocal microscopy were
      utilized for analyzing the levels, redistribution, and co-localization of Golgi
      apparatus and endosome or lysosome markers. Transient cerebral ischemia leads to
      delayed neuronal death that occurs at 48-72 h of reperfusion mainly in
      hippocampal CA1 and neocortical (Cx) layers 3 and 5 pyramidal neurons. During the
      delayed period, NSF ATPase is irreversibly trapped into inactive protein
      aggregates selectively in post-ischemic neurons destined to die. NSF inactivation
      leads to a massive buildup of Golgi fragments, transport vesicles (TVs) and late
      endosomes (LEs), and release of the 33 kDa LE type of CTSB, which is followed by
      delayed neuronal death after transient cerebral ischemia. The results support a
      novel hypothesis that transient cerebral ischemia leads to NSF inactivation,
      resulting in a cascade of events of fatal release of CTSB and delayed neuronal
      death after transient cerebral ischemia.

PMID- 29039035
TI  - Temporal dynamics of land use/land cover change and its prediction using CA-ANN
      model for southwestern coastal Bangladesh.
AB  - Change analysis of land use and land cover (LULC) is a technique to study the
      environmental degradation and to control the unplanned development. Analysis of
      the past changing trend of LULC along with modeling future LULC provides a
      combined opportunity to evaluate and guide the present and future land use
      policy. The southwest coastal region of Bangladesh, especially Assasuni Upazila
      of Satkhira District, is the most vulnerable to natural disasters and has faced
      notable changes in its LULC due to the combined effects of natural and
      anthropogenic causes. The objectives of this study are to illustrate the temporal
      dynamics of LULC change in Assasuni Upazila over the last 27 years (i.e., between
      1989 and 2015) and also to predict future land use change using CA-ANN (cellular
      automata and artificial neural network) model for the year 2028. Temporal
      dynamics of LULC change was analyzed, employing supervised classification of
      multi-temporal Landsat images. Then, prediction of future LULC was carried out by
      CA-ANN model using MOLUSCE plugin of QGIS. The analysis of LULC change revealed
      that the LULC of Assasuni had changed notably during 1989 to 2015. "Bare lands"
      decreased by 21% being occupied by other land uses, especially by "shrimp farms."
      Shrimp farm area increased by 25.9% during this period, indicating a major
      occupational transformation from agriculture to shrimp aquaculture in the study
      area during the period under study. Reduction in "settlement" area revealed the
      trend of migration from the Upazila. The predicted LULC for the year 2028 showed
      that reduction in bare land area would continue and 1595.97 ha bare land would
      transform into shrimp farm during 2015 to 2028. Also, the impacts of the changing
      LULC on the livelihood of local people and migration status of the Upazila were
      analyzed from the data collected through focus group discussions and
      questionnaire surveys. The analysis revealed that the changing LULC and the
      occupational shift from paddy cultivation to shrimp farming were related to each
      other. Around 31.3% of the total respondents stated that at least one of their
      family members had migrated. Climate-driven southwestern coastal people usually
      migrate from the vulnerable rural areas towards the nearest relatively safe city
      due to adverse effects of natural disasters. To control the unplanned development
      and reduce the internal migration in Assasuni and other coastal areas, a
      comprehensive land use management plan was suggested that would accommodate the
      diversified uses of coastal lands and eventually lessen the threats to the life
      and livelihood of the local people.

PMID- 29039036
TI  - Performance evaluation of two Aspergillus spp. for the decolourization of
      reactive dyes by bioaccumulation and biosorption.
AB  - A biological method was adopted to decolourize textile dyes, which is an economic
      and eco-friendly technology for textile wastewater remediation. Two fungal
      strains, i.e. Aspergillus lentulus and Aspergillus fumigatus, were used to study
      the removal of low to high concentrations (25 to 2000 mg L-1) of reactive remazol
      red, reactive blue and reactive yellow dyes by biosorption and bioaccumulation.
      The biosorption was successful only at the lower concentrations. A. lentulus was
      capable of removing 67-85% of reactive dyes during bioaccumulation mode of
      treatment at 500 mg L-1 dye concentration with an increased biomass uptake
      capacity. To cope up with the high dye concentration of 2000 mg L-1, a novel
      combined approach was successful in case of A. lentulus, where almost 76% removal
      of reactive remazol red dye was observed during bioaccumulation followed by
      biosorption. The scanning electron microscopy also showed the accumulation of dye
      on the surface of fungal mycelium. The results signify the application of such
      robust fungal strains for the removal of high concentration of dyes in the
      textile wastewaters.

PMID- 29039037
TI  - Amaranth seeds (Amaranthus palmeri L.) as novel feedstock for biodiesel
      production by oleaginous yeast.
AB  - The potential of lipid accumulation by oleaginous yeast Cryptococcus vishniaccii
      grown on amaranth seed aqueous extract (AAE) media was assessed. Maximum cell
      biomass productivity of 104 mg/L/h, lipid productivity of 54 mg/L/h, and lipid
      content of 52.31% were recorded on AAE when carbon to nitrogen (C:N) ratio
      increased from 134 to 147 after removal of ammonia nitrogen. The lipid droplet
      (LD) size (2.32 +/- 0.38 MUm) was visualized by fluorescence microscopy using
      Nile red stain indicating maximum accumulated triacylglycerol (TAG) at C:N 147.
      Fatty acid methyl ester (FAME) profile obtained after transesterification of
      extracted lipid revealed the presence of palmitic acid (16:0), palmitoleic acid
      (16:1), stearic acid (18:0), oleic acid (18:1), and linoleic acid (18:2). Data
      showed the presence of high monounsaturated fatty acid (MUFA) content (68.17%)
      depicting improved winter operating conditions of biodiesel. Various quality
      parameters of biodiesel were evaluated and compared to the American and European
      biodiesel standards specifications. Based on the lipid productivity, distribution
      of fatty acids, and evaluated properties obtained; the lipid accumulation by C.
      vishniaccii utilizing amaranth seeds as substrate could serve as a feasible
      feedstock for biodiesel production.

PMID- 29039038
TI  - Assessment of GHG mitigation and CDM technology in urban transport sector of
      Chandigarh, India.
AB  - The increase in number of vehicles in metropolitan cities has resulted in
      increase of greenhouse gas (GHG) emissions in urban environment. In this study,
      emission load of GHGs (CO, N2O, CO2) from Chandigarh road transport sector has
      been estimated using Vehicular Air Pollution Inventory (VAPI) model, which uses
      emission factors prevalent in Indian cities. Contribution of 2-wheelers (2-w), 3
      wheelers (3-w), cars, buses, and heavy commercial vehicles (HCVs) to CO, N2O,
      CO2, and total GHG emissions was calculated. Potential for GHG mitigation through
      clean development mechanism (CDM) in transport sector of Chandigarh under two
      scenarios, i.e., business as usual (BAU) and best estimate scenario (BES) using
      VAPI model, has been explored. A major contribution of GHG load (~ 50%) in
      Chandigarh was from four-wheelers until 2011; however, it shows a declining trend
      after 2011 until 2020. The estimated GHG emission from motor vehicles in
      Chandigarh has increased more than two times from 1065 Gg in 2005 to 2486 Gg by
      2011 and is expected to increase to 4014 Gg by 2020 under BAU scenario. Under BES
      scenario, 30% of private transport has been transformed to public transport; GHG
      load was possibly reduced by 520 Gg. An increase of 173 Gg in GHGs load is
      projected from additional scenario (ADS) in Chandigarh city if all the diesel
      buses are transformed to CNG buses by 2020. Current study also offers potential
      for other cities to plan better GHG reduction strategies in transport sector to
      reduce their climate change impacts.

PMID- 29039040
TI  - Effect of amount and duration of waste green tea powder on the growth
      performance, carcass characteristics, blood parameters, and lipid metabolites of
      growing broilers.
AB  - This study has evaluated the possible effect of waste powder of green tea
      (Camellia sinensis) in feed supplementation on the growth performance, carcass
      characteristics, blood parameters, and lipid metabolites of growing broilers
      (chicks) in both the amount and duration aspects of dietary additives during the
      finisher phases. In the experiment, growth performance, carcass characteristics,
      blood parameters, and lipid metabolites of broiler chicks have been fully
      recorded and explored. The diet of 271 day-old Ross 308 male broiler chicks has
      been supplemented with 0, 0.25, 0.50, 0.75, and 1.00% (w/w) green tea powder in
      addition to normal feeding additives. The experiment lasted for 21 and 42 days,
      respectively, for each value of the green tea supplement and for separate groups
      of animals. Broiler feed has been supplemented with different levels of green tea
      powder to assess the trial effect and potential beneficial dose on selected
      growth performance, carcass characteristics, and blood parameters of broiler
      chicks. Although there are almost no differences of broiler parameters and
      characteristics measured from one point of view of single treatment factor
      (amount or duration), against the control groups during the three trial periods,
      the overall effect of amount and duration of feeding green tea powder is positive
      on growth performance, carcass characteristics, blood parameters, and lipid
      metabolites of growing broilers, although there are nearly no differences in some
      broiler parameters and characteristics. However, there are a remarkable
      interactive effect of amount and duration of different feeding levels of green
      tea powder and obvious differences observed in all the parameters and
      characteristics of growing broilers. Especially, usage of feeding green tea
      powder largely decreased the abdominal fat content and some lipid metabolites,
      including VLDL cholesterol, LDL cholesterol, triglycerides, and AST of broiler
      chicks. While additional data are still needed to evaluate and analyze the
      optimum supplement feed doses, it can be concluded that dietary green tea is a
      positive feed supplementation to reduce abdominal fat and lipid metabolites and
      induce antioxidants.

PMID- 29039039
TI  - Biochar as an adsorbent for inorganic nitrogen and phosphorus removal from water:
      a review.
AB  - Biochar is the solid product of biomass pyrolysis that can be used for carbon
      sequestration, soil amendment, and pollution remediation. The use of biochar as
      an adsorbent for the removal of water contaminants has elicited increasing
      interest due to the multifunctional properties of this material. The application
      of biochar in the adsorption of inorganic nutrients from eutrophic water has not
      been reviewed. This review focuses on recent research on the use of biochar for
      the adsorption of inorganic nitrogen (ammonium and nitrate) and phosphorus
      (phosphate) from water, especially for the main influence factors and mechanisms
      for nitrogen and phosphorus adsorption on biochar.

PMID- 29039041
TI  - Evaluation of antioxidant potential of essential oils of some commonly used
      Indian spices in in vitro models and in food supplements enriched with omega-6
      and omega-3 fatty acids.
AB  - The aim of this study was to evaluate and compare the antioxidant potential of
      essential oils of some commonly used Indian spices (black pepper, cinnamon,
      clove, coriander and cumin) in various in vitro models and in food supplements
      enriched with omega-6 and omega-3 fatty acids. In vitro antioxidant potential was
      evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging and Fe2+
      ion-chelating methods and lipid oxidation stabilisation potential was evaluated
      in bulk soybean oil-fish oil mixture and their oil-in-water emulsions using
      peroxide value (PV), p-anisidine value (p-AV) and total oxidation value as
      indicators of oxidation. Combination effects using DPPH radical scavenging and
      Briggs-Rauscher oscillating reaction methods were also evaluated. Test essential
      oils showed varying degrees of radical scavenging and Fe2+ ion-chelating
      efficacy. Clove and coriander oils showed significantly higher (P < 0.05) radical
      scavenging and Fe2+ ion-chelating potential over other tested essential oils as
      well as BHT and infinity-tocopherol. The anti-lipid peroxidative potential of
      test essential oils was found in the following decreasing order: clove >
      coriander > BHT > cinnamon > alpha-tocopherol > cumin > black pepper.
      Furthermore, clove and coriander oils showed synergistic antioxidant activity in
      combination both in DPPH radical scavenging and Briggs-Rauscher oscillating
      reaction methods whereas other possible combinations showed additive effects.
      Strong radical scavenging and Fe2+-chelating as well as anti-lipid peroxidative
      activities of clove and coriander oils provide evidence that clove and coriander
      oils may serve as a potential source of natural antioxidants for retarding lipid
      oxidation of food supplements enriched with omega-6 and omega-3 fatty acids.

PMID- 29039042
TI  - Comparative responses of diazotrophic abundance and community structure to the
      chemical composition of paddy soil.
AB  - Diazotrophy is considered as one of the most crucial and dynamic phenomena in the
      rice field and also a major source of nitrogen input. The objective of this study
      was to elucidate possible interactions between diverse and dominant diazotrophic
      bacterial community and organic carbon composition of the paddy soil. Our results
      suggest that most abundantly found diazotrophs belong to a proteobacteria group
      and uncultured bacterial forms. A gene abundance study clearly showed
      significantly higher diazotrophic abundance (P < 0.01) at Chandauli (CHN) as
      compared to Varanasi (VNS) and Ghazipur (GHJ) districts of Eastern Uttar Pradesh,
      India, with nitrogenase reductase (nifH) copy number between 1.44 * 103 and 3.34
      * 103 copy g-1 soil. Fourier-transform infrared (FT-IR) spectroscopy data
      identified -CO-, C=O ([Formula: see text] and -NH-), [Formula: see text], and OH-
      as dominant organic functional groups in the paddy soil. Multivariate analysis
      was performed to get a clear and more accurate picture of interactions between
      free-living diazotrophs and abiotic soil factors. Regression analysis suggested a
      similar trend of distribution of different functional groups along each site.
      Relative abundance and diversity of diazotrophic population increased in response
      to FT-IR-based soil organic fractions. Maximum number of FT-IR spectral peak at
      sites in the Chandauli district augmented its bacterial diazotrophic diversity
      and abundance. Taken together, the present study sheds light on the substrate
      driven composition of the microbial population of selected paddy areas.

PMID- 29039043
TI  - Layer-dependent role of collagen recruitment during loading of the rat bladder
      wall.
AB  - In this work, we re-evaluated long-standing conjectures as to the source of the
      exceptionally large compliance of the bladder wall. Whereas these conjectures
      were based on indirect measures of loading mechanisms, in this work we take
      advantage of advances in bioimaging to directly assess collagen fibers and wall
      architecture during biaxial loading. A custom biaxial mechanical testing system
      compatible with multiphoton microscopy was used to directly measure the layer
      dependent collagen fiber recruitment in bladder tissue from 9 male Fischer rats
      (4 adult and 5 aged). As for other soft tissues, the bladder loading curve was
      exponential in shape and could be divided into toe, transition and high stress
      regimes. The relationship between collagen recruitment and loading curves was
      evaluated in the context of the inner (lamina propria) and outer (detrusor smooth
      muscle) layers. The large extensibility of the bladder was found to be possible
      due to folds in the wall (rugae) that provide a mechanism for low resistance
      flattening without any discernible recruitment of collagen fibers throughout the
      toe regime. For more extensible bladders, as the loading extended into the
      transition regime, a gradual coordinated recruitment of collagen fibers between
      the lamina propria layer and detrusor smooth muscle layer was found. A second
      important finding was that wall extensibility could be lost by premature
      recruitment of collagen in the outer wall that cut short the toe region. This
      change was correlated with age. This work provides, for the first time, a
      mechanistic understanding of the role of collagen recruitment in determining
      bladder extensibility and capacitance.

PMID- 29039044
TI  - Assessment of radon concentration and heavy metal contamination in groundwater of
      Udhampur district, Jammu & Kashmir, India.
AB  - Radon concentration was measured in water samples of 41 different locations from
      Udhampur district of Jammu & Kashmir, India, by using RAD7 and Smart RnDuo
      monitor. The variation of radon concentration in water ranged from 1.44 +/- 0.31
      to 63.64 +/- 2.88 Bq L-1, with a mean value of 28.73 Bq L-1 using RAD7 and 0.64
      +/- 0.28 to 52.65 +/- 2.50 Bq L-1, with a mean value of 20.30 Bq L-1 using Smart
      RnDuo monitor, respectively. About 17.07% of the studied water samples recorded
      to display elevated radon concentration above the reference range suggested by
      United Nation Scientific Committee on the Effects of Atomic Radiations (UNSCEAR).
      The mean annual effective dose of these samples was determined, and 78.95%
      samples were found to be within the safe limits set by World Health Organisation
      (WHO) and European Council (EU). The study revealed good agreement between the
      values obtained with two methods. Heavy metals (Zn, Cd, Fe, Cu, Ni, As, Hg, Co,
      Pb and Cr) were determined in water samples by microwave plasma atomic emission
      spectrometer, and their correlation with radon content was also analysed.

PMID- 29039045
TI  - Do age and linguistic background alter the audiovisual advantage when listening
      to speech in the presence of energetic and informational masking?
AB  - We examined how the type of masker presented in the background affected the
      extent to which visual information enhanced speech recognition, and whether the
      effect was dependent on or independent of age and linguistic competence. In the
      present study, young speakers of English as a first language (YEL1) and English
      as a second language (YEL2), as well as older speakers of English as a first
      language (OEL1), were asked to complete an audio (A) and an audiovisual (AV)
      speech recognition task in which they listened to anomalous target sentences
      presented against a background of one of three masker types (noise, babble, and
      competing speech). All three main effects were found to be statistically
      significant (group, masker type, A vs. AV presentation type). Interesting two-way
      interactions were found between masker type and group and between masker type and
      presentation type; however, no interactions were found between group (age and/or
      linguistic competence) and presentation type (A vs. AV). The results of this
      study, while they shed light on the effect of masker type on the AV advantage,
      suggest that age and linguistic competence have no significant effects on the
      extent to which a listener is able to use visual information to improve speech
      recognition in background noise.

PMID- 29039046
TI  - Reduced attentional focus and the influence on expert anticipatory perception.
AB  - The anticipatory memory encodings of expert and novice basketball players were
      examined under conditions of both full (attended condition) and reduced
      (unattended condition) attention (see also Gorman, Abernethy, & Farrow in
      Attention, Perception, & Psychophysics, 75, 835-844, 2013a). Participants
      completed a typical pattern recall task using dynamic playing sequences from
      basketball, and their responses were compared to both the original target pattern
      as well as to the series of patterns that occurred immediately after and
      immediately before the target image. The latter had not previously been employed
      in a pattern recall task when examining the anticipatory encoding of pattern
      information. Results revealed that the overall extent of the forward displacement
      for both the attended and unattended patterns was generally significantly greater
      for the experts, with the expert advantage tending to be most prominent for the
      attacking patterns. The novel addition of both forward and backward scenes may
      provide a more precise measure of the anticipatory effect, suggesting that future
      research in this domain should use a similar methodological design.

PMID- 29039047
TI  - The expression pattern of keratin 24 in tissue-engineered dermo-epidermal human
      skin substitutes in an in vivo model.
AB  - AIMS AND OBJECTIVES: The use of autologous tissue-engineered skin substitutes is
      a promising approach to cover large skin defects in patients. Preclinical
      investigation is pivotal to test and improve the quality of these bio-engineered
      substitutes. In the skin, the epidermis, formed mainly by keratinocytes, provides
      the first physical barrier protecting from the environment. Proper keratinocyte
      differentiation and, thus, formation of a stratified epidermis is essential for
      this function. Keratins, the main structural support of keratinocytes, play a
      vital role regarding differentiation of keratinocytes. Here, we examined the
      expression pattern of a recently described keratinocyte differentiation marker,
      namely Keratin 24, in our skin substitutes. MATERIALS AND METHODS: Human
      epidermal keratinocytes, melanocytes, dermal fibroblasts, palmar fibroblasts or
      sweat gland cells were used to prepare skin substitutes. Fibroblast-containing
      collagen hydrogels were prepared, and keratinocytes or sweat gland cells and
      melanocytes were seeded onto the hydrogels. The generated tissue-engineered dermo
      epidermal skin analogs were transplanted onto full-thickness skin wounds created
      on the back of immuno-incompetent rats. The skin substitutes were excised at
      different time points and histologically examined with regard to Keratin 24
      expression. RESULTS: We observed the expression of Keratin 24 in keratinocytes of
      the upper stratum spinosum of the epidermis. In particular, we observed an
      intensified expression of Keratin 24 13 weeks after transplantation compared to 4
      weeks after transplantation. Importantly, we noticed a markedly higher presence
      of Keratin 24 in more spinous layers if we used palmar fibroblasts or sweat gland
      cells in our skin substitutes compared non-palmar fibroblasts or epidermal
      keratinocytes. CONCLUSION: Our observations prove that the keratinocyte
      differentiation marker Keratin 24 is expressed in our dermo-epidermal skin
      substitutes in a normal pattern. This highlights that our bio-engineered skin
      analogs mature and reach homeostasis in an in vivo assay. These findings harbor
      favorable implications regarding future clinical application.

PMID- 29039048
TI  - Sclerosing and obstructive cholangiopathy in biliary atresia: mechanisms and
      association with biliary innate immunity.
AB  - Biliary atresia (BA) is histologically characterized by a progressive, sclerosing
      cholangitis and the obstruction of extrahepatic bile ducts. In terms of the
      etiology and pathogenesis of BA, several viral infections consisting of dsRNA,
      including Reoviridae, have been implicated. Human biliary epithelial cells (BECs)
      possess an innate immune system consisting of Toll-like receptors (TLRs). BECs
      have negative regulatory mechanisms of TLR tolerance to avoid an excessive
      inflammatory response to lipopolysaccharide (LPS), a TLR4 ligand; however, they
      lack the tolerance to poly(I:C) (a synthetic analog of viral dsRNA), a TLR3
      ligand. Treatment with poly(I:C) induces the expression of the apoptosis-inducer
      TNF-related apoptosis-inducing ligand (TRAIL), along with the antiviral molecule
      IFN-beta1, and reduces the viability of BECs by enhancing apoptosis. In response,
      surviving BECs increase their expression of various markers, including basic FGF
      [an epithelial-mesenchymal transition (EMT)-inducer], S100A4 (a mesenchymal
      marker), and Snail (a transcriptional factor), and decrease that of epithelial
      markers such as CK19 and E-cadherin before undergoing EMT. Extrahepatic bile
      ducts in BA infants frequently show a lack of epithelial markers and an aberrant
      expression of vimentin, in addition to the enhancement of TRAIL and apoptosis.
      dsRNA viruses may directly induce apoptosis and EMT in human BECs as a result of
      the biliary innate immune response, supporting the notion that Reoviridae
      infections may be directly associated with the pathogenesis of cholangiopathies
      in BA.

PMID- 29039049
TI  - Japanese Biliary Atresia Registry.
AB  - The Japanese Biliary Atresia Registry (JBAR) was launched in 1989 by the Japanese
      Biliary Atresia Society (JBAS). JBAR employed an initial questionnaire, a
      questionnaire for liver transplantation, and a follow-up questionnaire. The
      questionnaire has been sent to the pediatric surgeons of JBAS member institutions
      and the hospitals in which council members of the Japanese Society of Pediatric
      Surgeons are working. One hundred and twenty-three hospitals have been included
      in JBAR between 1989 and 2015. Each patient is to be followed up for 30 years.
      Between 1989 and 2015, 3160 patients have been registered in JBAR. Among them,
      1236 patients underwent liver transplantation. Follow-up questionnaire is also
      going on. 20-year overall and native-liver survival rates were 89 and 49%,
      respectively. The surgical outcome of BA has markedly improved owing to the co
      operation of Kasai portoenterostomy and liver transplantation. Japanese big
      database of BA is now available.

PMID- 29039051
TI  - Hidden morbidity of ethanol lock therapy.
AB  - AIMS: Long-term central venous catheters are essential in sustaining growth and
      development in patients with intestinal failure (IF). Several strategies have
      been developed to prevent and treat catheter-related blood stream infections
      (CRBSIs), including ethanol lock therapy. We sought to evaluate the efficacy of
      ethanol lock therapy in our IF population. METHOD: This is a retrospective review
      of IF patients treated with ethanol lock therapy at a single institution from
      2006 to 2013. We evaluated the number of catheter days, rate of CRBSI per 1000
      catheter days, rate of central venous catheter (CVC) thrombosis, rate of CVC
      breakage, total number of CVC replacements, total number of hospital admissions,
      and total number days in the hospital. RESULT: We identified 19 patients who
      underwent ethanol lock therapy for CRBSI. There was no difference in CRBSI rate
      prior to (5.6 per 1000 catheter days) and after (7 per 1000 catheter days)
      initiation of ethanol lock therapy. The mean rate of thrombosis increased from 0
      to 3 per 1000 catheter days with ethanol lock therapy (p < 0.05). In addition,
      the CVC breakage rate increased from 0 to 13.7 per 1000 catheter days with
      ethanol lock therapy (p < 0.001). Hospital admissions and catheter-related ER
      visits increased following the initiation of ethanol lock therapy. CONCLUSIONS:
      Contrary to other studies, there was no difference in CRBSI rate prior to and
      after initiation of ethanol lock therapy. Factors in the methodology of ethanol
      lock therapy may influence the effectiveness of infection prevention associated
      with ethanol lock therapy, as well as the rate of line breakage, line thrombosis,
      and the need for line replacement.

PMID- 29039050
TI  - The protective effect of fish oil lipid emulsions on intestinal failure
      associated liver disease in a rat model of short-bowel syndrome.
AB  - PURPOSE: Pediatric patients with intestinal failure need long-term parenteral
      nutrition (PN), but this nutritional support causes liver dysfunction, such as
      intestinal failure-associated liver disease (IFALD). Several studies have shown
      that the lipid emulsion produced by soybean oil (SO) is associated with the
      occurrence of IFALD. In this study, we evaluated the effect of SO and fish oil
      (FO) lipid emulsion on hepatic steatosis. METHODS: Sprague-Dawley rats underwent
      jugular vein catheterization and were divided into three groups: sham operation
      with normal chow (Sham group), 80% small bowel resection (80% SBR) + TPN with SO
      lipid emulsion (SO group), and 80% SBR + TPN with FO lipid emulsion (FO group).
      All rats were euthanized and the serum biochemistry and hepatic histology
      analyzed. RESULTS: No significant differences in the serum liver or biliary
      enzymes were noted between the SO and FO groups. The pathological findings and
      NAFLD score in the FO group did not show steatosis and were significantly lower
      than in the SO group. An analysis of the fatty acids profile in the both the SO
      and FO groups did not indicate essential fatty acid deficiency (EFAD).
      CONCLUSION: FO lipid emulsion may have a protective role against steatosis of
      IFALD without EFAD.

PMID- 29039052
TI  - Effect of Bariatric Surgery on Thyroid Function in Obese Patients: a Systematic
      Review and Meta-Analysis.
AB  - We aimed to make a meta-analysis regarding the effect of bariatric surgery on
      thyroid function in obese patients. PubMed, EMBASE, CENTRAL, and four Chinese
      databases were searched for clinical studies. Data were pooled using Review
      Manager 5.3, and subgroup and sensitivity analyses were performed if necessary
      and feasible. As a result, 24 articles were included into meta-analysis.
      Bariatric surgery was associated with significant decrease in TSH, FT3, and T3
      levels. However, FT4, T4, and rT3 levels were not significantly changed
      postoperatively. In addition, bariatric surgery had a favorable effect on overt
      and subclinical hypothyroid, with reduction of thyroid hormone requirements
      postoperatively. In conclusion, TSH, FT3, and T3 decrease are expected following
      bariatric surgery, as well as non-significant change of T4, FT4, and rT3 levels.

PMID- 29039053
TI  - Health Care Institutions Volume Is Significantly Associated with Postoperative
      Outcomes in Bariatric Surgery.
AB  - PURPOSE: The volume of bariatric surgery has significantly increased over the
      past decade with concomitant postoperative outcomes improvement. The goal of this
      nationwide study was to estimate the volume-outcome relationship in bariatric
      surgery at the hospital level. MATERIALS AND METHODS: A cross-sectional analysis
      of all patients who underwent bariatric surgery procedure in France from January
      2011 to December 2014 was designed. Volume-outcome relationship was analyzed
      using generalized estimating equations. RESULTS: We identified 184,332 inpatient
      stays for bariatric surgical procedures performed in 606 hospitals. Health care
      institutions performing more than 200 bariatric cases per year were significantly
      associated with shorter average length of stay (p < 0.001) and less frequent need
      for intensive or critical care unit (p = 0.003) during the index stay in
      comparison with lower volume institutions. Reoperations rate increased from 3.1%
      [95% CI, 2.8-3.3] (n = 5627) at 1 month to 4.9% [4.6-5.2] at 3 months and 8.2%
      [7.8-8.7] at 6 months. The risk of reoperation after gastric bypass was 1.37
      times less frequent in higher volume institutions (>= 200 inpatient stays per
      year, p = 0.003), while it was 1.26 times more frequent after gastric banding in
      higher volume institutions (p = 0.057) and was unaltered regarding sleeve
      gastrectomy (p = 0.819). CONCLUSION: This study showed for the first time in
      bariatric surgery that reoperation rate after gastric bypass or sleeve
      significantly increased at 3 and 6 months postoperatively. Health care
      institutions performing more than 200 bariatric cases per year were significantly
      associated with improved postoperative outcomes and less frequent need for
      reoperation.

PMID- 29039055
TI  - Treatment Patterns, Complications, and Health Care Utilization Among
      Endometriosis Patients Undergoing a Laparoscopy or a Hysterectomy: A
      Retrospective Claims Analysis.
AB  - INTRODUCTION: Hysterectomy and laparoscopy are common surgical procedures used
      for the treatment of endometriosis. This study compares outcomes for women who
      received either procedure within the first year post initial surgery. METHODS:
      The study used data from the Truven Health MarketScan claims databases from 2004
      to 2013 to identify women aged 18-49 years who received an endometriosis-related
      laparoscopy or hysterectomy. Patients were excluded if they did not have
      continuous insurance coverage from 1 year before through 1 year after their
      endometriosis-related procedure, if they were diagnosed with uterine fibroids
      prior to or on the date of surgery (i.e., index date), or if they had a
      hysterectomy prior to the index date. The descriptive analyses examined
      differences between patients with an endometriosis-related laparoscopy or
      hysterectomy in regard to medications prescribed, complications, and
      hospitalizations during the immediate year post procedure. RESULTS: The final
      sample consisted of 24,915 women who underwent a hysterectomy and 37,308 who
      underwent a laparoscopy. Results revealed significant differences between the
      cohorts, with women who received a laparoscopy more likely to be prescribed a
      GnRH agonist, progestin, danazol, or an opioid analgesic in the immediate year
      post procedure compared to women who underwent a hysterectomy. In contrast, women
      who underwent a hysterectomy generally had higher complication rates. Index
      hospitalization rates and length of stay (LOS) were higher for women who had a
      hysterectomy, while post-index hospitalization rates and LOS were higher for
      women who had a laparoscopy. For both cohorts, post-procedure complications were
      associated with significantly higher hospitalization rates and longer LOS.
      CONCLUSION: This study indicated significantly different 1-year post-surgical
      outcomes for patients who underwent an endometriosis-related hysterectomy
      relative to a laparoscopy. Furthermore, the endometriosis patients in this
      analysis had a considerable risk of surgical complications, subsequent surgeries,
      and hospital admissions, both during and after their initial therapeutic
      laparoscopy or hysterectomy. FUNDING: AbbVie.

PMID- 29039056
TI  - Emerging Concepts on Disease-Modifying Therapies in Type 1 Diabetes.
AB  - PURPOSE OF REVIEW: This review seeks to characterize emerging concepts related to
      disease-modifying therapy in type 1 diabetes. RECENT FINDINGS: We begin by
      describing the new understanding that islet autoimmunity, as identified by the
      presence of islet autoantibodies, inevitably leads to clinical type 1 diabetes.
      This understanding informs the new staging paradigm for type 1 diabetes, which
      suggests that type 1 diabetes may be recognized and diagnosed long before
      symptoms develop. Although it is known that nearly all individuals with
      established islet autoimmunity will eventually develop symptomatic type 1
      diabetes (T1D), individual characteristics such as age and biomarker profile may
      predict rate of disease progression and response to treatment and may therefore
      be used to individualize therapy. Key research supports the use of immunotherapy
      in TID, although a paradigm shift is necessary before immunotherapy may
      transition from clinical trials to clinical practice. Recent and ongoing research
      as it relates to these concepts is described throughout.

PMID- 29039057
TI  - The Effects of Low Doses of Gamma-Radiation on Growth and Membrane Activity of
      Pseudomonas aeruginosa GRP3 and Escherichia coli M17.
AB  - Microorganisms are part of the natural environments and reflect the effects of
      different physical factors of surrounding environment, such as gamma (gamma)
      radiation. This work was devoted to the study of the influence of low doses of
      gamma radiation with the intensity of 2.56 MUW (m2 s)-1 (absorbed doses were 3.8
      mGy for the radiation of 15 min and 7.2 mGy-for 30 min) on Escherichia coli M-17
      and Pseudomonas aeruginosa GRP3 wild type cells. The changes of bacterial,
      growth, survival, morphology, and membrane activity had been studied after gamma
      irradiation. Verified microbiological (specific growth rate, lag phase duration,
      colony-forming units (CFU) number, and light microscopy digital image analysis),
      biochemical (ATPase activity of bacterial membrane vesicles), and biophysical (H+
      fluxes throughout cytoplasmic membrane of bacteria) methods were used for
      assessment of radiation implications on bacteria. It was shown that growth
      specific rate, lag phase duration and CFU number of these bacteria were lowered
      after irradiation, and average cell surface area was decreased too. Moreover ion
      fluxes of bacteria were changed: for P. aeruginosa they were decreased and for E.
      coli-increased. The N,N'-dicyclohexylcarbodiimide (DCCD) sensitive fluxes were
      also changed which were indicative for the membrane-associated F0F1-ATPase
      enzyme. ATPase activity of irradiated membrane vesicles was decreased for P.
      aeruginosa and stimulated for E. coli. Furthermore, DCCD sensitive ATPase
      activity was also changed. The results obtained suggest that these bacteria
      especially, P. aeruginosa are sensitive to gamma radiation and might be used for
      developing new monitoring methods for estimating environmental changes after
      gamma irradiation.

PMID- 29039054
TI  - Treatment Persistence and Healthcare Costs Among Patients with Rheumatoid
      Arthritis Changing Biologics in the USA.
AB  - INTRODUCTION: After a patient with rheumatoid arthritis (RA) fails tumor necrosis
      factor inhibitor (TNFi) treatment, clinical guidelines support either cycling to
      another TNFi or switching to a different mechanism of action (MOA), but payers
      often require TNFi cycling before they reimburse switching MOA. This study
      examined treatment persistence, cost, and cost per persistent patient among MOA
      switchers versus TNFi cyclers. METHODS: This study of Commercial and Medicare
      Advantage claims data from the Optum Research Database included patients with RA
      and at least one claim for a TNFi (adalimumab, certolizumab pegol, etanercept,
      golimumab, or infliximab) between January 2012 and September 2015 who changed to
      another TNFi or a different MOA therapy (abatacept, tocilizumab, or tofacitinib)
      within 1 year. The index date was the date of the change in therapy. Treatment
      persistence was defined as no subsequent switch or 60-day gap in therapy for 1
      year post-index. RA-related costs included plan-paid and patient-paid amounts for
      inpatient, outpatient, and pharmacy claims. Medication costs included index and
      post-index costs of TNFi and different MOA therapies. RESULTS: There were 581
      (38.3%) MOA switchers and 935 (61.7%) TNFi cyclers. The treatment persistence
      rate was significantly higher for MOA switchers versus TNFi cyclers (47.7% versus
      40.2%, P = 0.004). Mean 1-year healthcare costs were significantly lower among
      MOA switchers versus TNFi cyclers for total RA-related costs ($37,804 versus
      $42,116; P < 0.001) and medication costs ($29,001 versus $34,917; P < 0.001).
      When costs were divided by treatment persistence, costs per persistent patient
      were lower among MOA switchers versus TNFi cyclers: $25,436 lower total RA
      related cost and $25,999 lower medication costs. CONCLUSION: MOA switching is
      associated with higher treatment persistence and lower healthcare costs than TNFi
      cycling. Reimbursement policies that require patients to cycle TNFi before
      switching MOA may result in suboptimal outcomes for both patients and payers.
      FUNDING: Sanofi and Regeneron Pharmaceuticals.

PMID- 29039058
TI  - Recurrent and de novo glomerulonephritis following renal transplantation: higher
      rates of rejection and lower graft survival.
AB  - PURPOSE: In this retrospective study with case-control design, we aimed to
      determine the clinical and pathological characteristics of post-transplant
      glomerulonephritis (GN), and their effects on transplant recipients. METHODS: One
      hundred and twenty renal transplant recipients with biopsy-proven recurrent or de
      novo primary GN were compared with two matched control groups including 120
      transplant recipients with nonrecurrent primary GN (nonrecurrent GN group) and
      120 transplant recipients with non-GN etiology (non-GN group). Primary outcome
      was allograft loss, and secondary outcomes were biopsy-confirmed cellular or
      antibody-mediated rejection. RESULTS: In recurrent/de novo GN, nonrecurrent GN
      and non-GN groups, 54.2% (n = 65), 16.7% (n = 20) and 8.3% (n = 10) of patients
      reached primary outcome after a median follow-up of 96 (IQR: 56-149) months,
      respectively. Allograft loss was significantly higher in recurrent/de novo GN
      group compared to nonrecurrent GN and non-GN groups (p < 0.001). At 10 years,
      allograft loss rates in recurrent/de novo GN group were 54.2% for focal segmental
      glomerulosclerosis, 53.2% for membranoproliferative glomerulonephritis, and 33.4%
      for IgA nephropathy cases. Biopsy-confirmed rejection rate was significantly
      higher in the recurrent/de novo GN group (n = 25, 20.8%) compared to non-GN (n =
      8, 6.7%) group (p = 0.001). CONCLUSIONS: Recurrent/de novo GN is associated with
      higher risk of rejection and worse allograft survival.

PMID- 29039059
TI  - Modified tubularized incised plate urethroplasty reduces the risk of fistula and
      meatal stenosis for proximal hypospadias: a report of 63 cases.
AB  - PURPOSE: To report the feasibility of modified tubularized incised plate (TIP)
      urethroplasty technique for proximal hypospadias in 63 cases. METHODS: From
      January 2004 to March 2010, 63 patients underwent one-stage TIP urethroplasty
      (modified Snodgrass technique repair) using 2-3 of three covering layers (corpus
      spongiosum, dartos, and tunica vaginalis). The primary meatus was proximal
      penile, penoscrotal, scrotal, and perineal in 38, 13, 10, and 2 patients,
      respectively. All patients had chordee that was corrected with dorsal plication.
      Glanuloplasty was performed in all cases. Complications and cosmetic results were
      documented after 6-72 months of follow-up. RESULTS: A total of 63 boys with
      proximal hypospadias underwent Snodgrass hypospadias repair at a mean age of 8.5
      months (range 6-54). Mean operative time was 210 +/- 35 min. Patients were
      followed up with 6-month intervals for up to 6 years postoperatively. After 6
      years of follow-up, nine urethrocutaneous fistulae, four bleeding, four meatal
      stenoses, and one urethral stricture were reported. Cosmetic result was
      satisfactory according to parent's opinion and another surgeon. No residual
      chordee was observed in any cases (without artificial correction). CONCLUSION: In
      conclusion, this preliminary report can be estimated as an alternative technique
      with acceptable complication and cosmetic results for proximal hypospadias
      correction.

PMID- 29039060
TI  - The incidence of urinary tract cancers is related to preserved diuresis: a single
      center report.
AB  - PURPOSE: Residual diuresis progressively decreases with longer dialysis vintage,
      and higher incidence of renal and urinary tract cancers was often observed in
      hemodialyzed patients compared to the general population so we hypothesized that
      patients without preserved residual diuresis have higher risk of renal and
      urinary tract cancers than patients with preserved residual diuresis. METHODS:
      Retrospective clinical data and pathology reports were completed for 307 uremic
      patients undergoing chronic hemodialysis. Patients were divided into two
      subgroups regarding residual diuresis: the first group with residual diuresis <
      500 mL, 133 of 173 (76.8%) patients from this group were completely anuric, and
      the second group with 134 patients with residual diuresis > 500 mL. RESULTS: Site
      and type-specific cancers in our population of ESRD patients were all localized
      in estrogen-positive receptor organs. The increased risk of all types of urinary
      tract cancers occurred in the whole group, men and women, when compared to
      general population. There were a significantly higher number of patients with all
      types of cancers in the group with residual diuresis < 250 mL compared to
      patients with residual diuresis > 500 mL. Importantly, all urinary tract cancers
      were present in patients with residual diuresis < 500 mL. CONCLUSION: Higher
      incidence of urinary tract cancers found in ESRD patients undergoing chronic
      hemodialysis is associated with lost residual diuresis. Residual diuresis in
      these patients might be considered a risk marker for future urinary tract cancers
      as well as already established markers.

PMID- 29039061
TI  - EROD activity, chromosomal damage, and oxidative stress in response to
      contaminants exposure in tree swallow (Tachycineta bicolor) nestlings from Great
      Lakes Areas of Concern.
AB  - Tree swallow, Tachycineta bicolor, nestlings were collected from 60 sites in the
      Great Lakes, which included multiple sites within 27 Areas of Concern (AOCs) and
      six sites not listed as AOCs from 2010 to 2014. Nestlings, approximately 12 days
      of-age, were evaluated for ethoxyresorufin-O-dealkylase (EROD) activity,
      chromosomal damage, and six measures of oxidative stress. Data on each of these
      biomarkers were divided into four equal numbered groups from the highest to
      lowest values and the groups were compared to contaminant concentrations using
      multivariate analysis. Contaminant concentrations, from the same nestlings,
      included polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers
      (PBDEs), perfluorinated compounds (PFCs), and 17 elements. Alkylated polycyclic
      aromatic hydrocarbons (aPAHs) and parent PAHs (pPAHs) were measured in pooled
      nestling dietary samples. Polychlorinated dibenzo-p-dioxins, polychlorinated
      dibenzofurans, and pesticides were measured in sibling eggs. Concentrations of
      aPAHs, pPAHs, chlordane, dieldrin, heptachlor, and PCBs, in that order, were the
      major contributors to the significant differences between the lowest and highest
      EROD activities; PFCs, PBDEs, the remaining pesticides, and all elements were of
      secondary importance. The four categories of chromosomal damage did not separate
      out well based on the contaminants measured. Concentrations of aPAHs, pPAHs,
      heptachlor, PCBs, chlordane, and dieldrin were the major contributors to the
      significant differences between the lowest and highest activities of two
      oxidative stress measures, total sulfhydryl (TSH) activity and protein bound
      sulfhydryl (PBSH) activity. The four categories of thiobarbituric acid reacting
      substances (TBARS), oxidized glutathione (GSSG), reduced glutathione (GSH), and
      the ratio of GSSG/GSH did not separate well based on the contaminants measured.

PMID- 29039064
TI  - Developments in Hematopoietic Stem Cell Expansion and Gene Editing Technologies.
AB  - Hematopoietic stem cells (HSCs) are rare cells, which housed in the adult bone
      marrow. They maintain all types of differentiated blood cells throughout life.
      Due to limited availability of HSCs for transplantation, treatment of various
      inherited bone marrow disorders and anemia requires the development of HSC
      expansion and gene editing technologies. To this end, various studies addressed
      the use of cytokines and growth factors for HSC expansion. Major hurdle with
      these studies was found to be spontaneous differentiation of HSCs into different
      lineages during ex vivo procedure. In addition, cost efficient approaches were
      needed. Thus, studies move on to the identification of small molecules and
      development of RNA interference technologies with potential to enhance cell cycle
      progression and block inhibitory signaling mechanisms during ex vivo HSC
      expansion as well as single cell expansion of HSCs following gene editing
      studies. This review aims to highlight developments in hematopoietic stem cells
      expansion and gene editing technologies.

PMID- 29039065
TI  - Conversations with a Master Cancer Educator: Joseph F. O'Donnell, M.D.

PMID- 29039063
TI  - Evaluation of the use of the fourth version FloTrac system in cardiac output
      measurement before and after cardiopulmonary bypass.
AB  - The FloTrac system is a system for cardiac output (CO) measurement that is less
      invasive than the pulmonary artery catheter (PAC). The purposes of this study
      were to (1) compare the level of agreement and trending abilities of CO values
      measured using the fourth version of the FloTrac system (CCO-FloTrac) and PAC
      originated continuous thermodilution (CCO-PAC) and (2) analyze the inadequate CO
      discriminating ability of the FloTrac system before and after cardiopulmonary
      bypass (CPB). Fifty patients were included. After exclusion, 32 patients
      undergoing cardiac surgery with CPB were analyzed. All patients were monitored
      with a PAC and radial artery catheter connected to the FloTrac system. CO was
      assessed at 10 timing points during the surgery. In the Bland-Altman analysis,
      the percentage errors (bias, the limits of agreement) of the CCO-FloTrac were
      61.82% (0.16, - 2.15 to 2.47 L min) and 51.80% (0.48, - 1.97 to 2.94 L min)
      before and after CPB, respectively, compared with CCO-PAC. The concordance rates
      in the four-quadrant plot were 64.10 and 62.16% and the angular concordance rates
      (angular mean bias, the radial limits of agreement) in the polar-plot analysis
      were 30.00% (17.62 degrees , - 70.69 degrees  to 105.93 degrees ) and 38.63% (-
      10.04 degrees , - 96.73 degrees  to 76.30 degrees ) before and after CPB,
      respectively. The area under the receiver operating characteristic curve for CCO
      FloTrac was 0.56, 0.52, 0.52, and 0.72 for all, >= +/- 5, >= +/- 10, and >= +/-
      15% CO changes (DeltaCO) of CCO-PAC before CPB, respectively, and 0.59, 0.55,
      0.49, and 0.46 for all, >= +/- 5, >= +/- 10, and >= +/- 15% DeltaCO of CCO-PAC
      after CPB, respectively. When CO < 4 L/min was considered inadequate, the Cohen
      kappa coefficient was 0.355 and 0.373 before and after CPB, respectively. The
      accuracy, trending ability, and inadequate CO-discriminating ability of the
      fourth version of the FloTrac system in CO monitoring are not statistically
      acceptable in cardiac surgery.

PMID- 29039062
TI  - Assessment of liver perfusion and function by indocyanine green in the
      perioperative setting and in critically ill patients.
AB  - Indocyanine green (ICG) is a water-soluble dye that is bound to plasma proteins
      when administered intravenously and nearly completely eliminated from the blood
      by the liver. ICG elimination depends on hepatic blood flow, hepatocellular
      function and biliary excretion. ICG elimination is considered as a useful dynamic
      test describing liver function and perfusion in the perioperative setting, i.e.,
      in liver surgery and transplantation, as well as in critically ill patients. ICG
      plasma disappearance rate (ICG-PDR) which can be measured today by transcutaneous
      systems at the bedside is a valuable method for dynamic assessment of liver
      function and perfusion, and is regarded as a valuable prognostic tool in
      predicting survival of critically ill patients, presenting with sepsis, ARDS or
      acute liver failure.

PMID- 29039066
TI  - Pattern Classification of Enterovirus 71-Associated Hand, Foot, and Mouth Disease
      in Chinese Medicine: A Retrospective Study in 433 Cases.
AB  - OBJECTIVE: To determine whether patterns of enterovirus 71 (EV71)-associated
      hand, foot, and mouth disease (HFMD) were classified based on symptoms and signs,
      and explore whether individual characteristics were correlated with membership in
      particular pattern. METHODS: Symptom-based latent class analysis (LCA) was used
      to determine whether patterns of EV71-HFMD existed in a sample of 433 cases from
      a clinical data warehouse system. Logistic regression was then performed to
      explore whether demographic, and laboratory data were associated with pattern
      membership. RESULTS: LCA demonstrated a two-subgroup solution with an optimal
      fit, deduced according to the Bayesian Information Criterion minima. Hot pattern
      (59.1% of all patients) was characterized by a very high fever and high
      endorsement rates for classical HFMD symptoms (i.e., rash on the extremities,
      blisters, and oral mucosa lesions). Non-hot pattern (40.9% of all patients) was
      characterized by classical HFMD symptoms. The multiple logistic regression
      results suggest that white blood cell counts and aspartate transaminase were
      positively correlated with the hot pattern (adjust odds ratio=1.07, 95%
      confidence interval: 1.006-1.115; adjust odds ratio=1.051, 95% confidence
      interval: 1.019-1.084; respectively). CONCLUSIONS: LCA on reported symptoms and
      signs in a retrospective study allowed different subgroups with meaningful
      clinical correlates to be defined. These findings provide evidence for targeted
      prevention and treatment interventions.

PMID- 29039067
TI  - In Silico System Pharmacology for the Potential Bioactive Ingredients Contained
      in Xingnaojing Injection () and Its Material Basis for Sepsis Treatment.
AB  - OBJECTIVE: To elucidate the action mechanism of Xingnaojing Injection (, XNJI)
      for sepsis, and to target screen the potential bioactive ingredients. METHODS: An
      integrated protocol that combines in silico target screen (molecular docking) and
      database mapping was employed to find the potential inhibitors from XNJI for the
      sepsis-related targets and to establish the compound-target (C-T) interaction
      network. The XNJI's bioactive components database was investigated and the sepsis
      associated targets were comprehensively constructed; the 3D structure of
      adenosine receptor A2a and 5-lipoxygenase proteins were established and evaluated
      with homology modeling method; system network pharmacology for sepsis treatment
      was studied between the bioactive ingredients and the sepsis targets using
      computational biology methods to distinguish inhibitors from non inhibitors for
      the selected sepsis-related targets and C-T network construction. RESULTS:
      Multiple bioactive compounds in the XNJI were found to interact with multiple
      sepsis targets. The 32 bioactive ingredients were generated from XNJI in
      pharmacological system, and 21 potential targets were predicted to the sepsis
      disease; the biological activities for some potential inhibitors had been
      experimentally confirmed, highlighting the reliability of in silico target
      screen. Further integrated C-T network showed that these bioactive components
      together probably display synergistic action for sepsis treatment. CONCLUSIONS:
      The uncovered mechanism may offer a superior insight for understanding the theory
      of the Chinese herbal medicine for combating sepsis. Moreover, the potential
      inhibitors for the sepsis-related targets may provide a good source to find new
      lead compounds against sepsis disease.

PMID- 29039068
TI  - The effect of scan interval and bolus length on the quantitative accuracy of
      cerebral computed tomography perfusion analysis using a hollow-fiber phantom.
AB  - The shuttle scan technique is expected to extend scan range in cerebral computed
      tomography (CT) perfusion by 16- or 64-row multidetector CT (MDCT), but it may
      affect quantitative accuracy. This study aims to evaluate the effect of long scan
      interval and bolus length on the quantitative accuracy of perfusion indices using
      an innovative hollow-fiber phantom.We used an originally developed hollow-fiber
      hemodialyzer covered with polyurethane resin as a perfusion phantom. We scanned
      the phantom during various scan intervals (1-13 s) and bolus injection lengths
      (5, 10, 15, and 20 s), and evaluated cerebral blood flow (CBF), cerebral blood
      volume (CBV), mean transit time (MTT), and time-to-peak (TTP). We verified the
      influence on measured values using a two-way analysis of variance (ANOVA). All
      measured CBF values were smaller than the theoretical CBF values, and all the
      measured MTT values were larger that the theoretical MTT values (95% confidence
      interval). Extended scan intervals resulted in more overestimation of MTT and
      more underestimation of CBF (p < 0.001). CBV is not affected by the change in
      scan interval (p < 0.001), and a longer bolus length improved the underestimation
      of CBV (p < 0.001). Extended scan intervals resulted in the loss of quantitative
      accuracy in MTT, even with longer bolus injection length, while quantitative CBF
      values were underestimated and TTP values overestimated. The CBV measurement was
      not affected by the change in scan interval, and a longer bolus injection
      improved the accuracy of these measurements.

PMID- 29039069
TI  - Prefoveal floaters as a differential diagnosis to optic neuritis: ''mouches
      dormantes''.

PMID- 29039070
TI  - The evaluation of xenotransplantation of feline ovarian tissue vitrified by
      needle immersed vitrification technique into male immunodeficient mice.
AB  - In this study, the efficiency of the "Needle Immersed Vitrification" technique
      was tested on cryopreserved feline ovarian tissue. For vitrification, ovarian
      fragments (0.5-1.5 mm2) from each ovary were collected; the grafts were exposed
      to 7.5-15% ethylene glycol and 7.5-15% dimethyl sulfoxide at room temperature and
      stored in liquid nitrogen at least 1 week. Morphologic examinations, expression
      of genes such as B cell lymphoma 2, B-cell lymphoma-2-associated X protein, Bone
      morphogenetic protein 15, zone of polarizing activity, zona pellucida C protein
      and DNA (cytosine-5)-methyltransferase 1, ultrastructural analysis and viability
      tests were carried out from collected grafts. Light microscopy examinations
      revealed the percentage of morphologically normal primordial follicles in a fresh
      group which was significantly higher than the treatment groups (p < 0.001).
      Terminal deoxynucleotidyl transferase dUTP nick end labeling and anti-caspase-3
      staining observed in oocytes, follicle cells, interstitial tissue showed higher
      rates of apoptosis for post-vitrification and -transplantation groups than
      freshly grafted ovarian tissues. Furthermore, we observed significant
      downregulation of zone of polarizing activity and zona pellucida C protein gene
      expression in vitrified ovarian tissue grafts than in the fresh grafts (p <
      0.05). In conclusion, we suggest that the needle immersed vitrification method is
      a convenient, cheap, and feasible vitrification method for cat ovarian tissues.
      However, further studies need to be performed to determine more optimal
      vitrification solutions and equilibration times for the needle immersed
      vitrification method in order to adapt it for cat ovaries.

PMID- 29039071
TI  - Potential Applications of Gliclazide in Treating Type 1 Diabetes Mellitus:
      Formulation with Bile Acids and Probiotics.
AB  - A major advancement in therapy of type 1 diabetes mellitus (T1DM) is the
      discovery of new treatment which avoids and even replaces the absolute
      requirement for injected insulin. The need for multiple drug therapy of
      comorbidities associated with T1DM increases demand for developing novel
      therapeutic alternatives with new mechanisms of actions. Compared to other
      sulphonylurea drugs used in the treatment of type 2 diabetes mellitus, gliclazide
      exhibits a pleiotropic action outside pancreatic beta cells, the so-called
      extrapancreatic effects, such as antiinflammatory and cellular protective
      effects, which might be beneficial in the treatment of T1DM. Results from in vivo
      experiments confirmed the positive effects of gliclazide in T1DM that are even
      more pronounced when combined with other hypoglycaemic agents such as probiotics
      and bile acids. Even though the exact mechanism of interaction at the molecular
      level is still unknown, there is a clear synergistic effect between gliclazide,
      bile acids and probiotics illustrated by the reduction of blood glucose levels
      and improvement of diabetic complications. Therefore, the manipulation of bile
      acid pool and intestinal microbiota composition in combination with old drug
      gliclazide could be a novel therapeutic approach for patients with T1DM.

PMID- 29039072
TI  - First-line bolus 5-fluorouracil plus leucovorin for peritoneally disseminated
      gastric cancer with massive ascites or inadequate oral intake.
AB  - BACKGROUND: There are few chemotherapeutic options for advanced gastric cancer
      with severe disseminated peritoneal metastases, which are usually accompanied by
      ascites. Bolus 5-fluorouracil (5-FU) plus leucovorin therapy has been widely used
      against gastrointestinal malignancies, with resulting mild toxicities. METHODS:
      We retrospectively analyzed the efficacy and safety of first-line chemotherapy
      with bolus 5-FU plus l-leucovorin in 30 advanced gastric cancer patients who had
      massive ascites and/or inadequate oral intake. This therapy consisted of 5-FU
      (600 mg/m2 IV bolus) plus l-leucovorin (250 mg/m2 2-h IV infusion) administered
      on a 6 weeks on/2 weeks off schedule. RESULTS: Among all the patients, 26 (87%)
      were unable to eat and 12 (40%) had massive ascites. Major grade 3 or 4 adverse
      events were neutropenia (17%), nausea (7%), fatigue (7%), and diarrhea (3%); no
      treatment-related deaths were observed. The median progression-free survival and
      overall survival (OS) were 2.4 months [95% confidence interval (CI), 0.6-4.1] and
      6.0 months (95% CI, 2.1-9.9), respectively. Objective improvement in oral intake
      was seen in 7 patients (27%). Improvement in ascites occurred in 9 (39%) of 23
      patients. In multivariate analyses, the presence of both massive ascites and
      inadequate oral intake was significantly associated with worse OS (hazard ratio,
      5.25; 95% CI, 1.61-17.1). The median OS for patients (n = 22) without this factor
      was 7.2 months (95% CI, 4.2-10.3). CONCLUSION: Our study suggests that bolus 5-FU
      plus l-leucovorin therapy is feasible and has clinical activity as palliative
      therapy in patients with severe peritoneal metastases from gastric cancer.

PMID- 29039073
TI  - A double-blind randomized phase II dose-finding study of olanzapine 10 mg or 5 mg
      for the prophylaxis of emesis induced by highly emetogenic cisplatin-based
      chemotherapy.
AB  - PURPOSE: The aim of this phase II study was to evaluate the efficacy and safety
      of two doses (10 and 5 mg) of olanzapine in combination with standard antiemetic
      treatment (aprepitant, palonosetron, and dexamethasone) for patients receiving
      highly emetogenic chemotherapy (HEC). METHODS: A multi-institutional, double
      blind, randomized phase II, dose-finding study of olanzapine was performed in
      patients with a malignant solid tumor who were receiving HEC with cisplatin (>=
      50 mg/m2). Patients were randomly assigned either olanzapine 10 or 5 mg orally on
      days 1-4, combined with standard antiemetic treatment. The primary endpoint was a
      complete response (CR; no emesis and no use of rescue medications) in the delayed
      phase (24-120 h after the start of cisplatin treatment). RESULTS: 153 patients
      were randomized to the 10 mg group (n = 76) or the 5 mg group (n = 77). The CR
      rate in the delayed phase was 77.6% (80% CI: 70.3-83.8, P = 0.01) in the 10 mg
      group and 85.7% (80% CI: 79.2-90.7, P < 0.001) in the 5 mg group (P value for H
      0: complete response rate <= 65%). The most common adverse event was somnolence,
      which had an incidence of 53.3 and 45.5% in the 10 and 5 mg olanzapine groups,
      respectively. CONCLUSIONS: Both doses of 10 and 5 mg olanzapine provided a
      significant improvement in delayed emesis. A dose of 5 mg olanzapine was
      determined as the recommended dose for a further phase III study based on higher
      CR and lower somnolence rates. CLINICAL TRIAL INFORMATION: UMIN000014214.

PMID- 29039074
TI  - The usefulness of stereo-electroencephalography (SEEG) in the surgical management
      of focal epilepsy associated with "hidden" temporal pole encephalocele: a case
      report and literature review.
AB  - The authors report a case of 18-year-old woman with partial complex seizures
      compatible with temporal epilepsy by semiology. Due to medical refractoriness,
      she was referred to pre-surgical evaluation. Initially, MRI showed no significant
      structural abnormality and superficial scalp EEG demonstrated epileptiform
      activity in the frontotemporal areas. Due to the lack of clear MRI abnormalities
      and the potential involvement of dominant mesial temporal structures by seizure
      semiology and non-invasive data, extra-operative invasive evaluation using stereo
      electroencephalography (SEEG) methodology was indicated. Invasive monitoring
      demonstrated seizure onset in the left temporal pole with early spread to
      ipsilateral amygdala. Surgical treatment resulted in resection of the temporal
      pole and amygdala, with preservation of the remaining mesial temporal lobe
      structures. Intraoperatively, it was observed that multiple dural defects in the
      anterior middle temporal fossa with invagination of adjacent temporal pole
      parenchyma are compatible with temporal encephalocele. Patient remains seizure
      free since surgery (12 months follow-up period) with preservation of
      neuropsychological functions. Although temporal pole resection plus
      amygdalohippocampectomy has been described as an adequate surgical approach in
      temporal encephalocele cases, we demonstrated the usefulness of the SEEG
      methodology in minimizing the volume of temporal lobe resection without
      compromising seizure and neuropsychological outcomes. The optimal results in this
      case and the review of the literature may suggest that in medically refractory
      epilepsies caused by temporal pole encephaloceles, preservation of the temporal
      lobe mesial structures should be attempted.

PMID- 29039075
TI  - Venous thromboembolism and intracranial hemorrhage after craniotomy for primary
      malignant brain tumors: a National Surgical Quality Improvement Program analysis.
AB  - Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and
      pulmonary embolism (PE), frequently complicates the postoperative course of
      primary malignant brain tumor patients. Thromboprophylactic anticoagulation is
      commonly used to prevent VTE at the risk of intracranial hemorrhage (ICH). We
      extracted all patients who underwent craniotomy for a primary malignant brain
      tumor from the National Surgical Quality Improvement Program (NSQIP) registry
      (2005-2015) to perform a time-to-event analysis and identify relevant predictors
      of DVT, PE, and ICH within 30 days after surgery. Among the 7376 identified
      patients, the complication rates were 2.6, 1.5, and 1.3% for DVT, PE, and ICH,
      respectively. VTE was the second-most common major complication and third-most
      common reason for readmission. ICH was the most common reason for reoperation.
      The increased risk of VTE extends beyond the period of hospitalization,
      especially for PE, whereas ICH occurred predominantly within the first days after
      surgery. Older age and higher BMI were overall predictors of VTE. Dependent
      functional status and longer operative times were predictive for VTE during
      hospitalization, but not for post-discharge events. Admission two or more days
      before surgery was predictive for DVT, but not for PE. Preoperative steroid usage
      and male gender were predictive for post-discharge DVT and PE, respectively. ICH
      was associated with various comorbidities and longer operative times. This
      multicenter study demonstrates distinct critical time periods for the development
      of thrombotic and hemorrhagic events after craniotomy. Furthermore, the VTE risk
      profile depends on the type of VTE (DVT vs. PE) and clinical setting
      (hospitalized vs. post-discharge patients).

PMID- 29039076
TI  - Evaluation of the Diversity of Probiotic Bacillus, Clostridium, and
      Bifidobacterium Using the Illumina-Based Sequencing Method.
AB  - Bacterial species of Bacillus, Lactobacillus, and Bifidobacterium in the
      intestinal tract have been used as probiotics. Selections for probiotic
      candidates by the culture-based approaches are time-consuming and labor
      consuming. The aim of this study was to develop a new method based on sequencing
      strategies to select the probiotic Bacillus, Lactobacillus, and Bifidobacterium.
      The Illumina-based sequencing strategies with different specific primers for
      Bacillus, Clostridium, and Bifidobacterium were applied to analyze diversity of
      the genera in goat feces. The average number of different Bacillus, Clostridium,
      and Bifidobacterium OTUs (operational taxonomic units) at the 97% similarity
      level ranged from 1922 to 63172. The coverage index values of Bacillus,
      Clostridium, and Bifidobacterium calculated from the bacterial OTUs were 0.89,
      0.99, and 1.00, respectively. The most genera of Bacillus (37.9%), Clostridium
      (53%), and Bifidobacterium (99%) were detected in goat feces by the Illumina
      based sequencing with the specific primers of the genera, respectively. Higher
      phylogenetic resolutions of the genera in goat feces were successfully
      established. The results suggest that the selection for probiotic Bacillus,
      Clostridium, and Bifidobacterium based on the Illumina sequencing with their
      specific primers is reliable and feasible, and the core Bacillus, Clostridium,
      and Bifidobacterium species of healthy goats possess the potentials as probiotic
      microbial consortia.

PMID- 29039077
TI  - Chronic light exposure alters serotonergic and orexinergic systems in the rat
      brain and reverses maternal separation-induced increase in orexin receptors in
      the prefrontal cortex.
AB  - Maternal separation (MS) is a well-established rodent model of depression.
      Chronic constant light (CCL) treatment during adolescence has been shown to
      reverse the depression-like behaviour induced by MS. We aimed to further
      delineate the antidepressant effect of light by investigating the involvement of
      the dopaminergic, serotonergic and orexinergic systems. MS was used to induce
      changes in adult male Sprague-Dawley rats, some of whom were also treated with
      CCL for 3 weeks during adolescence. At P80, rats were decapitated and brain
      tissue collected for analysis of glutamate- and potassium-stimulated dopamine
      release in the nucleus accumbens (NAc) using an in vitro superfusion technique.
      Enzyme-linked immunosorbent assays were employed to measure 5-hydroxytryptamine
      (5-HT) levels in the hypothalamus and prefrontal cortex (PFC). Western blotting
      was used to measure orexin receptor 1 (OXR-1) and 2 (OXR-2) in the PFC. MS did
      not affect 5-HT levels in these rats. However, CCL increased hypothalamic 5-HT
      and reduced 5-HT levels in the PFC. CCL had opposite effects on OXR levels in the
      PFC of maternally separated and non-separated rats. MS increased OXR-1 and OXR-2
      levels in the PFC, an effect that was normalized by CCL treatment. MS reduced
      glutamate-stimulated dopamine release in the NAc, an effect that was not reversed
      by CCL. The present results suggest that CCL treatment affects 5-HT and
      orexinergic systems in the MS model while not affecting the MS-induced decrease
      in dopamine release in the NAc. The reversal of changes in the orexinergic system
      may be of particular relevance to the antidepressant effect of CCL in depression.

PMID- 29039078
TI  - The neuroprotective effects of hydro-alcoholic extract of olive (Olea europaea
      L.) leaf on rotenone-induced Parkinson's disease in rat.
AB  - Parkinson's disease (PD) is an age-related disease in which dopaminergic neurons
      in the nigrostriatal pathway are destroyed, resulting in movement and behavioral
      problems. Oxidative stress and the generation of reactive oxygen species play key
      roles in neurodegenerative diseases, such as PD. Rotenone (ROT) is a common
      pesticide that induces oxidative stress. Olive leaves extract (OLE) has
      antioxidant and neuroprotective effects. Thus, the aim of this study was to
      investigate the neuroprotective effects of OLE on ROT-induced oxidative stress in
      the midbrain of a rat model of PD. Ninety-six Wistar rats were randomly divided
      into the following 6 groups (n = 16 rats/group): Control, Sham, ROT, and 3 ROT +
      OLE (75, 150, and 300 mg/kg/daily) groups. ROT (2.5 mg/kg/48 h) was injected
      subcutaneously, and vehicle or OLE was orally administered for 30 days. The
      animals were then sacrificed, and their brains were removed. Biochemical
      measures, including the levels of catalase (CAT), glutathione peroxidase (GPx),
      superoxide dismutase (SOD), and malondialdehyde (MDA), and the number of tyrosine
      hydroxylase (TH)-positive neurons were determined, and behavioral (rotarod and
      hanging) tests were conducted. The balance and muscle strength of the OLE (150
      and 300 mg/kg)-treated groups were significantly improved. Treatment with OLE
      prevented the increases in the levels of MDA, significantly improved the SOD,
      CAT, and GPx levels in the midbrain, and prevented the depletion of the TH
      positive neurons. These findings suggested that OLE has neuroprotective
      properties and that it might be useful for preventing the death of dopaminergic
      neurons in patients with PD.

PMID- 29039080
TI  - Preface.

PMID- 29039079
TI  - A long-term survivor of hilar cholangiocarcinoma with resection of recurrent
      peritoneal dissemination after R0 surgery: a case report.
AB  - BACKGROUND: Although hilar cholangiocarcinoma (HCCA) has a very poor prognosis,
      there are cases in which long-term survival is rarely obtained by
      multidisciplinary treatment. CASE PRESENTATION: A 61-year-old man diagnosed with
      HCCA was referred to our hospital. We performed an extended left hemi-hepatectomy
      and caudate lobectomy with extrahepatic bile duct resection. The tumor stage was
      T2aN0M0, stage II, based on the TNM classification, seventh edition. R0 resection
      was successfully performed. Adjuvant chemotherapy was not administered. After 38
      months, computed tomography revealed peritoneal dissemination. The patient
      received chemotherapy with tegafur-gimeracil-oteracil-potassium (S-1) and
      gemcitabine. The peritoneal dissemination was successfully controlled for more
      than 50 months. During the treatment, levels of CEA and CA19-9 kept rising
      slowly, which was followed by bowel obstruction due to peritoneal dissemination
      of HCCA. The patient underwent resection of transverse colon with tumor nodules,
      and the tumor was pathologically diagnosed as metastasis of HCCA. Tumor markers
      decreased to normal levels, and the patient has been free from tumor relapse for
      6 months. CONCLUSIONS: We here report a rare case of HCCA patient with recurrent
      peritoneal dissemination 3 years after R0 surgery which was sensitive to
      chemotherapy. The patient successfully received resection of peritoneal
      dissemination 50 months after the induction of chemotherapy and survived for 10
      years.

PMID- 29039081
TI  - Proteasome dysregulation in human cancer: implications for clinical therapies.
AB  - Cancer cells show heightened dependency on the proteasome for their survival,
      growth, and spread. Proteasome dysregulation is therefore commonly selected in
      favor of the development of many types of cancer. The vast abnormalities in a
      cancer cell, on top of the complexity of the proteasome itself, have enabled a
      plethora of mechanisms gearing the proteasome to the oncogenic process. Here, we
      use selected examples to highlight some general mechanisms underlying proteasome
      dysregulation in cancer, including copy number variations, transcriptional
      control, epigenetic regulation, and post-translational modifications. Research in
      this field has greatly advanced our understanding of proteasome regulation and
      will shed new light on proteasome-based combination therapies for cancer
      treatment.

PMID- 29039083
TI  - Myristoylated alanine-rich C kinase substrate (MARCKS): a multirole signaling
      protein in cancers.
AB  - Emerging evidence implicates myristoylated alanine-rich C-kinase substrate
      (MARCKS), a major substrate of protein kinase C (PKC), in a critical role for
      cancer development and progression. MARCKS is tethered to the plasma membrane but
      can shuttle between the cytosol and plasma membrane via the myristoyl
      electrostatic switch. Phosphorylation of MARCKS by PKC leads to its translocation
      from the plasma membrane to the cytosol where it functions in actin cytoskeletal
      remodeling, Ca2+ signaling through binding to calmodulin, and regulation of
      exocytic vesicle release in secretory cells such as neurons and airway goblet
      cells. Although the contribution of MARCKS to various cellular processes has been
      extensively studied, its roles in neoplastic disease have been conflicting. This
      review highlights the molecular and functional differences of MARCKS that exist
      between normal and tumor cells. We also discuss the recent advances in the
      potential roles of MARCKS in tumorigenesis, metastasis, and resistance to anti
      cancer therapies, with a focus on addressing the inconsistent results regarding
      the function of MARCKS as a promoter or inhibitor of oncogenesis.

PMID- 29039084
TI  - Use of coronary artery calcium scanning as a triage for invasive coronary
      angiography.

PMID- 29039085
TI  - Safer stress tests for myocardial perfusion imaging.

PMID- 29039086
TI  - And in the end....

PMID- 29039087
TI  - Can FDG-PET imaging play a role in guiding indications to endovascular treatments
      in patients presenting acute aortic syndromes?

PMID- 29039082
TI  - Metal-based proteasomal deubiquitinase inhibitors as potential anticancer agents.
AB  - Deubiquitinases (DUBs) play an important role in protein quality control in
      eukaryotic cells due to their ability to specifically remove ubiquitin from
      substrate proteins. Therefore, recent findings have focused on the relevance of
      DUBs to cancer development, and pharmacological intervention on these enzymes has
      become a promising strategy for cancer therapy. In particular, several DUBs are
      physically and/or functionally associated with the proteasome and are attractive
      targets for the development of novel anticancer drugs. The successful clinical
      application of cisplatin in cancer treatment has prompted researchers to develop
      various metal-based anticancer agents with new properties. Recently, we have
      reported that several metal-based drugs, such as the antirheumatic gold agent
      auranofin (AF), the antifouling paint biocides copper pyrithione (CuPT) and zinc
      pyrithione (ZnPT), and also our two synthesized complexes platinum pyrithione
      (PtPT) and nickel pyrithione (NiPT), can target the proteasomal DUBs UCHL5 and
      USP14. In this review, we summarize the recently reported small molecule
      inhibitors of proteasomal DUBs, with a focus on discussion of the unique nature
      of metal-based proteasomal DUB inhibitors and their anticancer activity.

PMID- 29039088
TI  - Evaluating Nanomedicines: Obstacles and Advancements.
AB  - Continued advancements in nanotechnology are expanding the boundaries of medical
      research, most notably as drug delivery agents for treatment against cancer. Drug
      delivery with nanotechnology can offer greater control over the biodistribution
      of therapeutic agents to improve the therapeutic index. In the last 20 years, a
      number of nanomedicines have transitioned into the clinic. As nanomedicines
      evolve, techniques to properly evaluate their safety and efficacy must also
      evolve. Characterization methods for nano-based materials must be adapted to the
      demands of nanomedicine developers and regulators. This second edition book
      provides updated characterization protocols designed to address the clinical
      potential of nanomedicines during their preclinical development. In this chapter,
      the characterization challenges of nanoparticles intended for drug delivery will
      be discussed, along with examples of advancements and improvements in
      nanomedicine characterization.

PMID- 29039089
TI  - Detection of Bacterial Contamination in Nanoparticle Formulations by Agar Plate
      Test.
AB  - Bacterial contamination can confound the results of in vitro and in vivo
      preclinical tests. This protocol describes a procedure for detection of microbial
      contamination in nanotechnology-based formulations. Nanoparticle samples and
      controls are spread on the surface of agar and growth of bacterial colonies is
      monitored after 72 h of incubation. The intended purpose of this assay is to
      avoid introduction of microbial contamination into in vitro cell cultures and in
      vivo animal studies utilizing the test nanomaterial. This assay is not intended
      to certify the material as sterile.

PMID- 29039090
TI  - Considerations and Some Practical Solutions to Overcome Nanoparticle Interference
      with LAL Assays and to Avoid Endotoxin Contamination in Nanoformulations.
AB  - Monitoring endotoxin contamination in drugs and medical devices is required to
      avoid pyrogenic response and septic shock in patients receiving these products.
      Endotoxin contamination of engineered nanomaterials and nanotechnology-based
      medical products represents a significant translational hurdle. Nanoparticles
      often interfere with an in vitro Limulus Amebocyte Lysate (LAL) assay commonly
      used in the pharmaceutical industry for the detection and quantification of
      endotoxin. Such interference challenges the preclinical development of
      nanotechnology-formulated drugs and medical devices containing engineered
      nanomaterials. Protocols for analysis of nanoparticles using LAL assays have been
      reported before. Here, we discuss considerations for selecting an LAL format and
      describe a few experimental approaches for overcoming nanoparticle interference
      with the LAL assays to obtain more accurate estimation of endotoxin contamination
      in nanotechnology-based products. The discussed approaches do not solve all types
      of nanoparticle interference with the LAL assays but could be used as a starting
      point to address the problem. This chapter also describes approaches to prevent
      endotoxin contamination in nanotechnology-formulated products.

PMID- 29039091
TI  - Elemental Analysis in Biological Matrices Using ICP-MS.
AB  - The increasing exploration of metallic nanoparticles for use as cancer
      therapeutic agents necessitates a sensitive technique to track the clearance and
      distribution of the material once introduced into a living system. Inductively
      coupled plasma mass spectrometry (ICP-MS) provides a sensitive and selective tool
      for tracking the distribution of metal components from these nanotherapeutics.
      This chapter presents a standardized method for processing biological matrices,
      ensuring complete homogenization of tissues, and outlines the preparation of
      appropriate standards and controls. The method described herein utilized gold
      nanoparticle-treated samples; however, the method can easily be applied to the
      analysis of other metals.

PMID- 29039092
TI  - PEG Quantitation Using Reversed-Phase High-Performance Liquid Chromatography and
      Charged Aerosol Detection.
AB  - This chapter describes a method for the quantitation of polyethylene glycol (PEG)
      in PEGylated colloidal gold nanoparticles using a reversed-phase high-performance
      liquid chromatography (RP-HPLC) with charged aerosol detection. The method can be
      used to calculate the total PEG on the nanoparticle, as well as the bound and
      free unbound PEG fractions after a simple centrifugation step. This is a
      significant distinction as the bound PEG fraction affects biocompatibility,
      circulation time, and overall nanoparticle efficacy. PEG quantitation can be
      achieved through two methods, one involving the dissolution of colloidal gold
      nanoparticles by potassium cyanide (KCN) and the other by displacement of PEG by
      dithiothreitol (DTT). The methods outlined herein were applied to 30 nm colloidal
      gold grafted with 20 kDa PEG, but they can be easily adapted to any size
      colloidal gold nanoparticle and PEG chain length.

PMID- 29039093
TI  - Quantitation of Surface Coating on Nanoparticles Using Thermogravimetric
      Analysis.
AB  - Nanoparticles are critical components in nanomedicine and nanotherapeutic
      applications. Some nanoparticles, such as metallic nanoparticles, consist of a
      surface coating or surface modification to aid in its dispersion and stability.
      This surface coating may affect the behavior of nanoparticles in a biological
      environment, thus it is important to measure. Thermogravimetric analysis (TGA)
      can be used to determine the amount of coating on the surface of the
      nanoparticle. TGA experiments run under inert atmosphere can also be used to
      determine residual metal content present in the sample. In this chapter, the TGA
      technique and experimental method are described.

PMID- 29039094
TI  - Immunoelectron Microscopy for Visualization of Nanoparticles.
AB  - Immunoelectron microscopy (IEM) on a solid phase such as a carbon film is a fast
      and powerful way to detect and visualize surface antigens on nanoparticles by
      using a transmission electron microscope (TEM). Nanoparticles, in particular ones
      for medical applications, are often modified on the surface with soft materials
      to make them more soluble, less toxic, or targetable to cancerous tumors. Imaging
      the soft material on the surface of solid nanoparticles by electron microscopy is
      often a challenge. IEM can overcome this issue in cases where antibodies to any
      of the surface material are available, which is often the case for proteins, but
      also for commonly used materials such as polyethylene glycol (PEG). This
      effective procedure has been used traditionally for viruses and macromolecules,
      but it can be directly applied to nanoparticles.

PMID- 29039095
TI  - Imaging of Liposomes by Transmission Electron Microscopy.
AB  - TEM is an important method for the characterization of size and shape of
      nanoparticles as it can directly visualize single particles and even their inner
      architecture. Imaging of metal particles in the electron microscope is quite
      straightforward due to their high density and stable structure, but the structure
      of soft material nanoparticles, such as liposomes, needs to be preserved for the
      electron microscope. The best method to visualize liposomes close to their native
      structure is cryo-electron microscopy, where thin films of suspensions are plunge
      frozen to create vitrified ice films that can be imaged directly in the electron
      microscope under liquid nitrogen temperature. Although subject to artifacts,
      negative staining TEM can also be a useful method to image liposomes, as it is
      faster and simpler than cryo-EM, and requires less advanced equipment.

PMID- 29039096
TI  - Updated Method for In Vitro Analysis of Nanoparticle Hemolytic Properties.
AB  - Hemolysis is damage to red blood cells (RBCs), which results in the release of
      the iron-containing protein hemoglobin into plasma. An in vitro assay was
      developed and described earlier for the analysis of nanoparticle hemolytic
      properties. Herein, we present a revised version of the original protocol. In
      this protocol, analyte nanoparticles and controls are incubated in blood.
      Undamaged RBCs are removed by centrifugation and hemoglobin, released by the
      damaged erythrocytes, is converted to cyanmethemoglobin by incubation with
      Drabkin's reagent. The amount of cyanmethemoglobin in the supernatant is measured
      by spectrophotometry. This measured absorbance is compared to a standard curve to
      determine the concentration of hemoglobin in the supernatant. The measured
      hemoglobin concentration is then compared to the total hemoglobin concentration
      to obtain the percentage of nanoparticle-induced hemolysis. The revision includes
      updated details about nanoparticle sample preparation, selection of nanoparticle
      concentration for the in vitro study, updated details about assay controls and
      case studies about nanoparticle interference with the in vitro hemolysis assay.

PMID- 29039097
TI  - In Vitro Assessment of Nanoparticle Effects on Blood Coagulation.
AB  - Blood clotting is a complex process which involves both cellular and biochemical
      components. The key cellular players in the blood clotting process are
      thrombocytes or platelets. Other cells, including leukocytes and endothelial
      cells, contribute to clotting by expressing the so-called pro-coagulant activity
      (PCA) complex on their surface. The biochemical component of blood clotting is
      represented by the plasma coagulation cascade, which includes plasma proteins
      also known as coagulation factors. The coordinated interaction between platelets,
      leukocytes, endothelial cells, and plasma coagulation factors is necessary for
      maintaining hemostasis and for preventing excessive bleeding. Undesirable
      activation of all or some of these components may lead to pathological blood
      coagulation and life-threatening conditions such as consumptive coagulopathy or
      disseminated intravascular coagulation (DIC). In contrast, unintended inhibition
      of the coagulation pathways may lead to hemorrhage. Thrombogenicity is the
      property of a test material to induce blood coagulation by affecting one or more
      elements of the clotting process. Anticoagulant activity refers to the property
      of a test material to inhibit coagulation. The tendency to cause platelet
      aggregation, perturb plasma coagulation, and induce leukocyte PCA can serve as an
      in vitro measure of a nanomaterial's likelihood to be pro- or anticoagulant in
      vivo. This chapter describes three procedures for in vitro analyses of platelet
      aggregation, plasma coagulation time, and activation of leukocyte PCA. Platelet
      aggregation and plasma coagulation procedures have been described earlier. The
      revision here includes updated details about nanoparticle sample preparation,
      selection of nanoparticle concentration for the in vitro study, and updated
      details about assay controls. The chapter is expanded to describe a method for
      the leukocyte PCA analysis and case studies demonstrating the performance of
      these in vitro assays.

PMID- 29039098
TI  - In Vitro Analysis of Nanoparticle Effects on the Zymosan Uptake by Phagocytic
      Cells.
AB  - This chapter provides a protocol for analysis of nanoparticle effects on the
      function of phagocytic cells. The protocol relies on luminol chemiluminescence to
      detect zymosan uptake. Zymosan is an yeast particle which is typically eliminated
      by phagocytic cells via the complement receptor pathway. The luminol, co
      internalized with zymosan, is processed inside the phagosome to generate a
      chemiluminescent signal. If a test nanoparticle affects the phagocytic function
      of the cell, the amount of phagocytosed zymosan and, proportionally, the level of
      generated chemiluminescent signal change. Comparing the zymosan uptake of
      untreated cells with that of cells exposed to a nanoparticle provides information
      about the nanoparticle's effects on the normal phagocytic function. This method
      has been described previously and is presented herein with several changes. The
      revised method includes details about nanoparticle concentration selection,
      updated experimental procedure, and examples of the method performance.

PMID- 29039099
TI  - Assessing NLRP3 Inflammasome Activation by Nanoparticles.
AB  - NLRP3 inflammasome activation is one of the initial steps in an inflammatory
      cascade against pathogen/danger-associated molecular patterns (PAMPs/DAMPs), such
      as those arising from environmental toxins or nanoparticles, and is essential for
      innate immune response. NLRP3 inflammasome activation in cells can lead to the
      release of IL-1beta cytokine via caspase-1, which is required for inflammatory
      induced programmed cell death (pyroptosis). Nanoparticles are commonly used as
      vaccine adjuvants and drug delivery vehicles to improve the efficacy and reduce
      the toxicity of chemotherapeutic agents. Several studies indicate that different
      nanoparticles (e.g., liposomes, polymer-based nanoparticles) can induce NLRP3
      inflammasome activation. Generation of a pro-inflammatory response is beneficial
      for vaccine delivery to provide adaptive immunity, a necessary step for
      successful vaccination. However, similar immune responses for intravenously
      injected, drug-containing nanoparticles can result in immunotoxicity (e.g.,
      silica nanoparticles). Evaluation of NLRP3-mediated inflammasome activation by
      nanoparticles may predict pro-inflammatory responses in order to determine if
      these effects may be mitigated for drug delivery or optimized for vaccine
      development. In this protocol, we outline steps to monitor the release of IL
      1beta using PMA-primed THP-1 cells, a human monocytic leukemia cell line, as a
      model system. IL-1beta release is used as a marker of NLRP3 inflammasome
      activation.

PMID- 29039100
TI  - Analysis of Complement Activation by Nanoparticles.
AB  - The complement system is a group of proteins, which function in plasma to assist
      the innate immunity in rapid clearance of pathogens. The complement system also
      contributes to coordination of the adaptive immune response. Complement
      Activation Related Pseudo Allergy or CARPA is a life-threatening condition
      commonly reported with certain types of drugs and nanotechnology-based
      combination products. While CARPA symptoms are similar to that of anaphylaxis,
      the mechanism behind this pathology does not involve IgE and is mediated by the
      complement system. In vitro assays using serum or plasma derived from healthy
      donor volunteers correlate with the in vivo complement-mediated reactions, and
      therefore are helpful in understanding the propensity of a given drug formulation
      to cause CARPA in patients. In the first edition of this book, we have described
      an in vitro method for qualitative assessment of the complement activation by
      nanomaterials using western blotting. Herein, we present a similar method
      utilizing enzyme-linked immunoassay for quantitative analysis of the complement
      activation, and we compare the performance of this approach to that of the
      qualitative western blotting technique. The revised chapter also includes new
      details about nanoparticle sample preparation.

PMID- 29039101
TI  - Methods for Analysis of Nanoparticle Immunosuppressive Properties In Vitro and In
      Vivo.
AB  - Adverse drug effects on the immune system function represent a significant
      concern in the pharmaceutical industry, because 10-20% of the drug withdrawal
      from the market is accounted to immunotoxicity. Immunosuppression is one such
      adverse effect. The traditional immune function test used to estimate materials'
      immunosuppression is a T-cell-dependent antibody response (TDAR). This method
      involves a 28 day in vivo study evaluating the animal's antibody titer to a known
      antigen (KLH) with and without challenge. Due to the limited quantities of novel
      drug candidates, an in vitro method called human leukocyte activation (HuLa)
      assay has been developed to substitute the traditional TDAR assay during early
      preclinical development. In this test, leukocytes isolated from healthy donors
      vaccinated with the current year's flu vaccine are incubated with Fluzone in the
      presence or absence of a test material. The antigen-specific leukocyte
      proliferation is then measured by ELISA analyzing incorporation of BrdU into DNA
      of the proliferating cells. Here, we describe the experimental procedures for
      investigating immunosuppressive properties of nanoparticles by both TDAR and HuLa
      assays, discuss the in vitro-in vivo correlation of these methods, and show a
      case study using the iron oxide nanoparticle formulation, Feraheme.

PMID- 29039103
TI  - Analysis of Nanoparticle-Adjuvant Properties In Vivo.
AB  - Nanoparticles can be engineered for targeted antigen delivery to the immune cells
      and for stimulating the immune response to improve the antigen immunogenicity.
      This approach is commonly used to develop nanotechnology-based vaccines. In
      addition, some nanotechnology platforms may be initially designed for drug
      delivery, but in the course of subsequent characterization, their additional
      immunomodulatory functions may be discovered that can potentially benefit vaccine
      efficacy. In both of these scenarios, an in vivo proof of concept study to verify
      the utility of the nanocarrier for improving vaccine efficacy is needed. Here, we
      describe an experimental approach and considerations for designing an animal
      study to test adjuvant properties of engineered nanomaterials in vivo.

PMID- 29039102
TI  - Analysis of Pro-inflammatory Cytokine and Type II Interferon Induction by
      Nanoparticles.
AB  - Cytokines, chemokines, and interferons are released by the immune cells in
      response to cellular stress, damage and/or pathogens, and are widely used as
      biomarkers of inflammation. Certain levels of cytokines are needed to stimulate
      an immune response in applications such as vaccines or immunotherapy where immune
      stimulation is desired. However, undesirable elevation of cytokine levels, as may
      occur in response to a drug or a device, may lead to severe side effects such as
      systemic inflammatory response syndrome or cytokine storm. Therefore, preclinical
      evaluation of a test material's propensity to cause cytokine secretion by healthy
      immune cells is an important parameter for establishing its safety profile.
      Herein, we describe in vitro methods for analysis of cytokines, chemokines, and
      type II interferon in whole blood cultures derived from healthy donor volunteers.
      First, whole blood is incubated with controls and tested nanomaterials for 24 h.
      Then, culture supernatants are analyzed by ELISA to detect IL-1beta, TNFalpha, IL
      8, and IFNgamma. The culture supernatants can also be analyzed for the presence
      of other biomarkers secreted by the immune cells. Such testing would require
      additional assays not covered in this chapter and/or optimization of the test
      procedure to include relevant positive controls and/or cell types.

PMID- 29039104
TI  - In Vitro and In Vivo Methods for Analysis of Nanoparticle Potential to Induce
      Delayed-Type Hypersensitivity Reactions.
AB  - Delayed-type hypersensitivity (DTH) reactions are among the common reasons for
      drug withdrawal from clinical use during the post-marketing stage. Several in
      vivo methods have been developed to test DTH responses in animal models. They
      include the local lymph node assay (LLNA) and local lymph node proliferation
      assay (LLNP). While LLNA is instrumental in testing topically administered
      formulations (e.g., creams), the LLNP was proven to be predictive of drug
      mediated DTH in response to small molecule pharmaceuticals. Global efforts in
      reducing the use of research animals lead to the development of in vitro models
      to predict test-material-mediated DTH. Two such models include analysis of
      surface marker expression in human cell lines THP-1 and U-937. These tests are
      known as the human cell line activation test (hCLAT) and myeloid U937 skin
      sensitization test (MUSST or U-SENS), respectively. Here we describe experimental
      procedures for all these methods, discuss their in vitro-in vivo correlation, and
      suggest a strategy for applying these tests to analyze engineered nanomaterials
      and nanotechnology-formulated drug products.

PMID- 29039105
TI  - Autophagy Monitoring Assay II: Imaging Autophagy Induction in LLC-PK1 Cells Using
      GFP-LC3 Protein Fusion Construct.
AB  - Autophagy is a catabolic process involved in the degradation and recycling of
      long-lived proteins and damaged organelles for maintenance of cellular
      homeostasis, and it has also been proposed as a type II cell death pathway. The
      cytoplasmic components targeted for catabolism are enclosed in a double-membrane
      autophagosome that merges with lysosomes, to form autophagosomes, and are finally
      degraded by lysosomal enzymes. There is substantial evidence that several
      nanomaterials can cause autophagy and lysosomal dysfunction, either by prevention
      of autophagolysosome formation, biopersistence or inhibition of lysosomal
      enzymes. Such effects have emerged as a potential mechanism of cellular toxicity,
      which is also associated with various pathological conditions. In this chapter,
      we describe a method to monitor autophagy by fusion of the modifier protein MAP
      LC3 with green fluorescent protein (GFP; GFP-LC3). This method enables imaging of
      autophagosome formation in real time by fluorescence microscopy without
      perturbing the MAP LC3 protein function and the process of autophagy. With the
      GFP-LC3 protein fusion construct, a longitudinal study of autophagy can be
      performed in cells after treatment with nanomaterials.

PMID- 29039106
TI  - Improved Ultrafiltration Method to Measure Drug Release from Nanomedicines
      Utilizing a Stable Isotope Tracer.
AB  - An important step in the early development of a nanomedicine formulation is the
      evaluation of stability and drug release in biological matrices. Additionally,
      the measurement of encapsulated and unencapsulated nanomedicine drug fractions is
      important for the determination of bioequivalence (pharmacokinetic equivalence)
      of generic nanomedicines. Unfortunately, current methods to measure drug release
      in plasma are limited, and all have fundamental disadvantages including non
      equilibrium conditions and process-induced artifacts. The primary limitation of
      current ultrafiltration (and equilibrium dialysis) methods for separation of
      encapsulated and unencapsulated drug and determination of drug release is the
      difficulty in accurately differentiating protein bound and encapsulated drug.
      Since the protein binding of most drugs is high (>70%) and can change in a
      concentration- and time-dependent manner, it is very difficult to accurately
      account for the fraction of non-filterable drug that is encapsulated within the
      nanomedicine and how much is bound to protein. The method in this chapter is an
      improvement of existing ultrafiltration protocols for nanomedicine fractionation
      in plasma, in which a stable isotope tracer is spiked into a nanomedicine
      containing plasma sample in order to precisely measure the degree of plasma
      protein binding. Determination of protein binding then allows for accurate
      calculation of encapsulated and unencapsulated nanomedicine drug fractions, as
      well as free and protein-bound fractions.

PMID- 29039107
TI  - Designing an In Vivo Efficacy Study of Nanomedicines for Preclinical Tumor Growth
      Inhibition.
AB  - Novel nanoformulated chemotherapeutics and diagnostics require demonstration of
      efficacy and safety in appropriate animal models prior to conducting early-phase
      clinical trials. In vivo efficacy experiments are tailored to the tumor model
      type and route of administration as well as several parameters related to the
      nanoformulation, like drug loading to determine dosing volume. When designing in
      vivo efficacy studies for nanomedicines, understanding the relationship between
      tumor biology and the nanoformulation characteristics is critical to achieving
      meaningful results, along with applying appropriate drug and nanoformulation
      controls. In particular, nanoparticles can have multifunctional roles such as
      targeting and imaging capabilities that require additional considerations when
      designing in vivo efficacy studies and choosing tumor models. In this chapter, we
      outline a general study design for a subcutaneously implanted tumor model along
      with an example of tumor growth inhibition and survival analysis.

PMID- 29039108
TI  - Preliminary results of a new workflow for MRI/CT-based image-guided brachytherapy
      in cervical carcinoma.
AB  - PURPOSE: We propose a method of image-guided brachytherapy (IGBT) that combines
      MRI-based target volume delineation for the first fraction with CT datasets of
      subsequent fractions, using an automatic, applicator-based co-registration, and
      report our preliminary experience. MATERIALS AND METHODS: The MRI of the first
      fraction was used for the first brachytherapy planning. For each subsequent
      brachytherapy fraction, after the same applicator insertion, a new CT scan with
      the applicator in place was obtained. The MR image set was registered to the
      subsequent brachytherapy treatment planning CT using the applicator for rigid
      body registration. To demonstrate the registration quality, we used here the Dice
      index as a measurement of tandem delineation overlap between CT and MRI. RESULTS:
      The median Dice index was 0.879 (range 0.610-0.932), which indicated that the
      contours on CT and MRI fitted well. With this combination method, the median D90
      of HR CTV and the calculated D2 cm3 of the bladder, rectum, and sigmoid in each
      fraction were 7.2 (4.0-10.4), 5.9 (2.3-7.7), 4.0 (1.9-6.7), and 3.8 (0.6-7.2) Gy,
      respectively. CONCLUSION: Our described method of MRI-guided IGBT offers a
      practical option for the benefits of target delineation.

PMID- 29039109
TI  - A novel utility of 99mTc-GSA SPECT/CT fusion imaging: detection of inadequate
      portal vein embolization.
AB  - PURPOSE: Our aim was to determine the utility of Tc-99m
      diethylenetriaminepentaacetic acid-galactosyl human serum albumin single-photon
      emission computed tomography (99mTc-GSA SPECT/CT) fusion imaging for detecting
      incomplete portal vein embolization (PVE). MATERIALS AND METHODS: Fifty-five
      candidates underwent PVE. Among them, five underwent second PVE. Detectability of
      first inadequate PVE using CT and 99mTc-GSA SPECT/CT fusion imaging was analyzed.
      RESULTS: Cases of inadequate PVE were detected in three patients using CT and in
      five using 99mTc-GSA SPECT/CT fusion imaging. Fusion imaging detected two cases
      of insufficient PVE in which portal branches were apparently well embolized on
      CT. Median value for volumetric rate in the embolized liver was 63.3% after the
      first PVE and 54.7% after the second (P < 0.01). Median functional rate value in
      embolized liver was 60.1% after the first PVE and 49.4% after the second (P <
      0.01). Median value for change of volumetric and functional rates in embolized
      liver after the second PVE was 7.1 and 10.3%, respectively, and change of
      functional rate was greater than that of volumetric rate (P < 0.01). CONCLUSIONS:
      99mTc-GSA SPECT/CT fusion imaging was useful for detecting inadequate PVE, and
      second PVE was effective for increasing volumetric and functional rates.

PMID- 29039110
TI  - Prognostic value of volumetric FDG PET/CT parameters in patients with oral tongue
      squamous cell carcinoma who were treated by superselective intra-arterial
      chemoradiotherapy.
AB  - PURPOSE: This study aimed to evaluate the predictive and prognostic value of FDG
      PET/CT-based volumetric parameters in patients with oral tongue squamous cell
      carcinoma (OTSCC) treated by superselective intra-arterial chemoradiotherapy (IA
      CRT). METHODS: We conducted a retrospective study including 33 patients with
      biopsy-proven OTSCC between May 2007 and February 2016. All of the patients were
      treated by IA-CRT. Pretreatment SUVmax and metabolic tumor volume (MTV) of the
      primary tumor were measured. The SUV thresholds of 2.5 and 5.0 were used.
      Progression-free survival (PFS) and overall survival (OS) were chosen as
      endpoints to evaluate prognosis. Univariate and multivariate analyses were
      performed to assess the potential independent effect of FDG PET/CT parameters.
      RESULTS: The median follow-up for surviving patients was 40.7 months (range 6.0
      107.5 months). In univariate and multivariate analyses, SUVmax and MTV (5.0) were
      independent prognostic factors for PFS. In univariate analysis, SUVmax failed to
      predict OS. MTV (5.0) was a significant prognostic factor for OS, but
      multivariate analysis failed to show statistical independence because it could
      not exclude the possibility of an artifact due to N stage. CONCLUSIONS: FDG
      PET/CT-based volumetric parameters may be significant prognostic markers for
      survival of patients with OTSCC who are treated by IA-CRT.

PMID- 29039112
TI  - James Cossar Ewart and the Origins of the Animal Breeding Research Department in
      Edinburgh, 1895-1920.
AB  - In 1919 the Animal Breeding Research Department was established in Edinburgh.
      This Department, later renamed the Institute of Animal Genetics, forged an
      international reputation, eventually becoming the centrepiece of a cluster of new
      genetics research units and institutions in Edinburgh after the Second World War.
      Yet despite its significance for institutionalising animal genetics research in
      the UK, the origins and development of the Department have not received as much
      scholarly attention as its importance warrants. This paper sheds new light on
      Edinburgh's place in early British genetics by drawing upon recently catalogued
      archival sources including the papers of James Cossar Ewart, Regius Professor of
      Natural History at the University of Edinburgh between 1882 and 1927. Although
      presently a marginal figure in genetics historiography, Ewart established two
      sites for experimental animal breeding work between 1895 and 1911 and played a
      central role in the founding of Britain's first genetics lectureship, also in
      1911. These early efforts helped to secure government funding in 1913. However, a
      combination of the First World War, bureaucratic problems and Ewart's personal
      ambitions delayed the creation of the Department and the appointment of its
      director by another six years. This paper charts the institutionalisation of
      animal breeding and genetics research in Edinburgh within the wider contexts of
      British genetics and agriculture in the early twentieth century.

PMID- 29039111
TI  - Hooking intestine sign: a typical diagnostic CT finding of Petersen's hernia.
AB  - PURPOSE: To clarify typical diagnostic computed tomography (CT) findings of
      Petersen's hernia for differentiation from other causes of internal hernia
      observed in patients having undergone gastrectomy with Roux-en-Y gastric bypass.
      METHODS: We retrospectively reviewed CT findings of internal hernia in patients
      who had undergone both gastrectomy and Roux-en-Y reconstruction and a second
      surgery for bowel obstruction. Thirteen patients with Petersen's hernia and 6
      with internal hernia other than Petersen's hernia were investigated. Six CT
      findings, viz. whirl sign, mesenteric fat haziness, intestinal distension in the
      upper abdomen, herniated intestinal loop above the gastric level, middle/distal
      ileum courses downwards from the left hypochondrium, and hooking intestine sign,
      which means two or more intestines pass through the inner side of J-shaped
      vessels consisting of mesenteric vessels of the elevated jejunum, were scored and
      evaluated regarding their diagnostic performance. RESULTS: The hooking intestine
      sign showed the highest sensitivity, specificity and accuracy (100%, 100% and
      100%). We could detect J-shaped vessels in all Petersen's hernia patients. Inside
      the J-shaped vessels there were two or more intestinal tracts passing through in
      the Petersen's hernia group. There was only transverse colon inside the J-shaped
      vessels in the control group. CONCLUSION: The hooking intestine sign may be
      useful for diagnosing Petersen's hernia on CT.

PMID- 29039113
TI  - A gastric glomus tumor resected using non-exposed endoscopic wall-inversion
      surgery.
AB  - Gastric glomus tumors are extremely rare, constituting approximately 1% of
      gastric mesenchymal tumors. We report the case of a 45-year-old female patient in
      whom upper gastrointestinal endoscopy revealed a 3-cm submucosal tumor with a
      bridging fold in the posterior wall of the antrum of the stomach. Contrast
      enhanced computed tomography revealed the tumor to be hypervascular in the
      arterial phase and exhibit continuous enhancement in the post-venous phase.
      Dynamic contrast-enhanced magnetic resonance imaging showed that the tumor was
      hypervascular in the early phase and persistently enhanced in the late phase.
      Endoscopic ultrasonography revealed a mosaic echo pattern. Endoscopic ultrasound
      guided fine-needle aspiration biopsy was performed. Immunohistochemical
      examination revealed that the tumor was positive for alpha-smooth muscle actin
      and synaptophysin, but negative for CD56, chromogranin A and C-kit. Furthermore,
      1-2% of the tumor cell nuclei were Ki-67-positive. Thus, the preoperative
      diagnosis was a benign glomus tumor. The patient then underwent non-exposed
      endoscopic wall-inversion surgery (NEWS), and the tumor was completely resected.
      In conclusion, NEWS is an effective method for the treatment of gastric glomus
      tumors.

PMID- 29039114
TI  - Long-term survival after repeated resection of metachronous lung metastases from
      pStage IA pancreatic adenocarcinoma.
AB  - CASE REPORT: A 70-year-old woman with pancreatic ductal adenocarcinoma was
      initially treated by distal pancreatectomy (DP). Thirty-five months later,
      another tumor appeared in the pancreatic head and was treated by
      pancreaticoduodenectomy. Histopathological findings identified both tumors as
      pancreatic ductal adenocarcinoma pStage IA. Computed tomography (CT) of the chest
      16 months after the second pancreatectomy revealed a ground-glass opacity in
      segment 3 of the right lung. Chest CT 23 months after the second pancreatectomy
      revealed a nodular shadow in segment 1a of the right lung. Chest CT 39 months
      after the second pancreatectomy revealed a nodular shadow in segment 5 of the
      left lung. These lesions were treated by video-assisted thoracoscopic surgery
      partial resection. Histopathological and immunohistochemical features (positive
      for cytokeratin (CK)7 and CK20, negative for transcription factor-1) for these
      three lesions and the secondary pancreatic ductal adenocarcinoma were similar,
      indicating a diagnosis of lung metastasis from the second pancreatic ductal
      adenocarcinoma. The patient has remained alive and free of new metastases for 8
      years after initial DP, 3 years after the last lung resection. CONCLUSION: This
      patient has survived over the long term after undergoing three resections of lung
      metastases from resected pancreatic ductal adenocarcinoma.

PMID- 29039116
TI  - Emigration Rates From Sample Surveys: An Application to Senegal.
AB  - What is the emigration rate of a country, and how reliable is that figure?
      Answering these questions is not at all straightforward. Most data on
      international migration are census data on foreign-born population. These migrant
      stock data describe the immigrant population in destination countries but offer
      limited information on the rate at which people leave their country of origin.
      The emigration rate depends on the number leaving in a given period and the
      population at risk of leaving, weighted by the duration at risk. Emigration
      surveys provide a useful data source for estimating emigration rates, provided
      that the estimation method accounts for sample design. In this study, emigration
      rates and confidence intervals are estimated from a sample survey of households
      in the Dakar region in Senegal, which was part of the Migration between Africa
      and Europe survey. The sample was a stratified two-stage sample with oversampling
      of households with members abroad or return migrants. A combination of methods of
      survival analysis (time-to-event data) and replication variance estimation
      (bootstrapping) yields emigration rates and design-consistent confidence
      intervals that are representative for the study population.

PMID- 29039115
TI  - Genome-Editing Technologies in Adoptive T Cell Immunotherapy for Cancer.
AB  - PURPOSE OF REVIEW: In this review, we discuss the most recent developments in
      gene-editing technology and discuss their application to adoptive T cell
      immunotherapy. RECENT FINDINGS: Engineered T cell therapies targeting cancer
      antigens have demonstrated significant efficacy in specific patient populations.
      Most impressively, CD19-directed chimeric antigen receptor T cells (CART19) have
      led to impressive responses in patients with B-cell leukemia and lymphoma.
      CTL019, or KYMRIAHTM (tisagenlecleucel), a CD19 CAR T cell product developed by
      Novartis and the University of Pennsylvania, was recently approved for clinical
      use by the Food and Drug Administration, representing a landmark in the
      application of adoptive T cell therapies. As CART19 enters routine clinical use,
      improving the efficacy of this exciting platform is the next step in broader
      application. Novel gene-editing technologies like CRISPR-Cas9 allow facile
      editing of specific genes within the genome, generating a powerful platform to
      further optimize the activity of engineered T cells.

PMID- 29039117
TI  - In Vivo Dentate Nucleus Gamma-aminobutyric Acid Concentration in Essential Tremor
      vs. Controls.
AB  - : Despite its high prevalence, essential tremor (ET) is among the most poorly
      understood neurological diseases. The presence and extent of Purkinje cell (PC)
      loss in ET is the subject of controversy. PCs are a major storehouse of central
      nervous system gamma-aminobutyric acid (GABA), releasing GABA at the level of the
      dentate nucleus. It is therefore conceivable that cerebellar dentate nucleus GABA
      concentration could be an in vivo marker of PC number. We used in vivo 1H
      magnetic resonance spectroscopy (MRS) to quantify GABA concentrations in two
      cerebellar volumes of interest, left and right, which included the dentate
      nucleus, comparing 45 ET cases to 35 age-matched controls. 1H MRS was performed
      using a 3.0-T Siemens Tim Trio scanner. The MEGA-PRESS J-editing sequence was
      used for GABA detection in two cerebellar volumes of interest (left and right)
      that included the dentate nucleus. The two groups did not differ with respect to
      our primary outcome of GABA concentration (given in institutional units). For the
      right dentate nucleus, [GABA] in ET cases = 2.01 +/- 0.45 and [GABA] in controls
      = 1.86 +/- 0.53, p = 0.17. For the left dentate nucleus, [GABA] in ET cases =
      1.68 +/- 0.49 and [GABA] controls = 1.80 +/- 0.53, p = 0.33. The controls had
      similar dentate nucleus [GABA] in the right vs. left dentate nucleus (p = 0.52);
      however, in ET cases, the value on the right was considerably higher than that on
      the left (p = 0.001). We did not detect a reduction in dentate nucleus GABA
      concentration in ET cases vs. CONTROLS: One interpretation of the finding is that
      it does not support the existence of PC loss in ET; however, an alternative
      interpretation is the observed pattern could be due to the effects of terminal
      sprouting in ET (i.e., collateral sprouting from surviving PCs making up for the
      loss of GABA-ergic terminals from PC degeneration). Further research is needed.

PMID- 29039118
TI  - A systematic review of flap fixation techniques in reducing seroma formation and
      its sequelae after mastectomy.
AB  - BACKGROUND: Seroma formation is a common complication after mastectomy. This
      review aims to elucidate which surgical techniques are most effective in reducing
      the dead space and therefore seroma formation in patients undergoing mastectomy.
      METHODS: A literature search was performed to identify clinical studies comparing
      any form of flap fixation to conventional closure technique in patients
      undergoing mastectomy with or without axillary clearance. Studies were eligible
      for inclusion if outcome was described in terms of seroma formation and/or
      complications of seroma formation. Studies on animal research or breast
      reconstruction with tissue expanders or flap harvesting (latissimus dorsi) were
      excluded. RESULTS: A total of nine articles were eligible for inclusion. Five
      were retrospective studies and four were prospective. Retrospective and
      prospective studies have demonstrated the higher incidence of seroma formation in
      patients not undergoing mechanical flap fixation. The incidence of seroma-related
      complications in these studies vary. Four out of the nine studies demonstrate
      that patients undergoing flap fixation, need significantly fewer seroma
      aspirations. There are very few studies on the use of tissue glues preventing
      seroma formation. CONCLUSION: The scientific body of evidence favoring flap
      fixation after mastectomy is convincing. Mechanical flap fixation seems to reduce
      seroma formation and seroma aspiration after mastectomy. There are, however, no
      well-powered randomized controlled trials evaluating all aspects of seroma
      formation and its sequelae. Further research should elucidate whether flap
      fixation using sutures or tissue glue is superior.

PMID- 29039119
TI  - Clinical implications of germline mutations in breast cancer: TP53.
AB  - PURPOSE: This review describes the prevalence of germline TP53 mutations, the
      risk of breast cancer and other cancers in mutation carriers and management
      implications for women with breast cancer and unaffected women. METHODS:
      Literature review of English language papers available through PubMed. RESULTS:
      Women who carry germline mutations in the TP53 gene have a very high risk of
      breast cancer of up to 85% by age 60 years. Most of these breast cancers are
      early onset with a median age at diagnosis of 34 years. Approximately 5-8% of
      women presenting with breast cancer under 30 years old have a germline TP53 gene
      mutation. Breast cancers in women with TP53 mutations are more likely to be
      hormone receptor positive and/or Her2 positive. Mastectomy is recommended over
      lumpectomy in TP53 mutation carriers who have breast cancer so that adjuvant
      breast radiotherapy can be avoided. Risk-reducing surgery should be considered
      due to the high contralateral breast cancer risk. Mutation carriers are at high
      risk of various childhood and adult-onset cancers with a very lifetime risk of
      malignancy, the commonest malignancies being breast cancer and soft tissue
      sarcoma. In unaffected female mutation carriers, MRI breast screening or risk
      reducing surgery is recommended. The optimal surveillance for other cancers is
      currently unclear and should ideally be performed as part of a clinical trial.
      CONCLUSIONS: Identifying a TP53 mutation in a gene panel test is a challenging
      result for the patient and clinician due to the high risk of second primaries and
      the lack of consensus about surveillance.

PMID- 29039121
TI  - Degradation of glycosphingolipids in oyster: ceramide glycanase and ceramidase in
      the hepatopancreas of oyster, Crassostrea virginica.
AB  - The hepatopancreas of oyster, Crassostrea virginica, was found to contain two
      unique glycosphingolipid (GSL) cleaving enzymes, ceramide glycanase (CGase) and
      ceramidase. These two enzymes were found to be tightly associated together
      through the consecutive purification steps including gel filtration, hydrophobic
      interaction and cation-exchange chromatographies. They were separated only by
      preparatory SDS-PAGE. The purified CGase was found to have a molecular mass of 52
      kDa and pH optimum of 3.2-3.3. This enzyme prefers to hydrolyze the acidic GSLs,
      II3SO3LacCer and gangliosides over the neutral GSLs. Oyster ceramidase was found
      to have a molecular mass of 88 kDa and pH optimum of 4-4.5. Since oyster
      ceramidase greatly prefers ceramides with C6 to C8 fatty acids, C6-ceramide (N
      hexanoyl-D-sphingosine) was used as the substrate for its purification and
      characterization. The oyster acid ceramidase also catalyzed the synthesis of
      ceramide from a sphingosine and a fatty acid. For the synthesis, C16 and C18
      fatty acids were the best precursors. The amino acid sequences of the two
      cyanogenbromide peptides derived from the purified ceramidase were found to have
      similarities to those of several neutral and alkaline ceramidases reported. The
      tight association of CGase and ceramidase may indicate that CGase in oyster
      hepatopancreas acts as a vehicle to release ceramide from GSLs for subsequent
      generation of sphingosines and fatty acids by ceramidase to serve as signaling
      factors and energy source.

PMID- 29039122
TI  - Why Psychiatric Education Needs the Humanities.

PMID- 29039120
TI  - Differential presentation and survival of de novo and recurrent metastatic breast
      cancer over time: 1990-2010.
AB  - BACKGROUND: Differences in de novo (dnMBC) and recurrent metastatic breast cancer
      (rMBC) presentation and survival over time have not been adequately described.
      METHODS: A retrospective cohort study, 1990-2010, with follow up through 2015 of
      dnMBC patients (stage IV at diagnosis) and rMBC patients with subsequent distant
      metastatic recurrence (stage I-III initial diagnosis) [dnMBC = 247, rMBC = 911)].
      Analysis included Chi squared tests of categorical variables, Kaplan-Meier
      survival estimates, and Cox proportional adjusted hazard ratios (HzR) and 95%
      confidence intervals (CI). Disease specific survival (DSS) was time from
      diagnosis or distant recurrence to BC death. RESULTS: Over time, 1990-1998, 1999
      2004, and 2005-2010, dnMBC incidence was constant (3%) and rMBC incidence
      decreased [18% to 7% (p < 0.001)] with no change in dnMBC hormone receptor (HR)
      or her2-neu (HER2) status but a decrease in rMBC HER2-positive cases and increase
      in triple negative breast cancer (HR-negative/HER2-negative) (p = 0.049). Five
      year dnMBC DSS was 44% vs. 21% for rMBC (p < 0.001). Five-year dnMBC DSS improved
      over time [28% to 55% (p = 0.008)] and rMBC worsened [23% to 13%, p = 0.065)].
      Worse DSS was associated with HR-negative status (HzR = 1.63; 1.41, 1.89), rMBC
      (HzR = 1.88; 1.58, 2.23), older age (70 +) (HzR = 1.88; 1.58, 2.24), > 1 distant
      metastases (HzR 1.39; 1.20, 1.62), and visceral dominant disease (HzR 1.22; 1.05,
      1.43). After 1998, HER2-positive disease was associated with better DSS (HzR =
      0.72, 95% CI 0.56, 0.93). CONCLUSIONS: Factors associated with the widening
      survival gap and non-equivalence between dnMBC and rMBC and decreased rMBC
      incidence warrant further study.

PMID- 29039123
TI  - Authors' Response to Comment on "Collaborative Training Efforts with Pediatric
      Providers in Addressing Mental Health Problems in Primary Care".

PMID- 29039124
TI  - Recent progress in mass spectrometry proteomics for biomedical research.
AB  - Proteins are the key players in many cellular processes. Their composition,
      trafficking, and interactions underlie the dynamic processes of life.
      Furthermore, diseases are frequently accompanied by malfunction of proteins at
      multiple levels. Understanding how biological processes are regulated at the
      protein level is critically important to understanding the molecular basis for
      diseases and often shed light on disease prevention, diagnosis, and treatment.
      With rapid advances in mass spectrometry (MS) instruments and experimental
      methodologies, MS-based proteomics has become a reliable and essential tool for
      elucidating biological processes at the protein level. Over the past decade, we
      have witnessed great expansion of knowledge of human diseases with the
      application of MS-based proteomic technologies, which has led to many exciting
      discoveries. Herein we review the recent progress in MS-based proteomics in
      biomedical research, including that in establishing disease-related proteomes and
      interactomes. We also discuss how this progress will benefit biomedical research
      and clinical diagnosis and treatment of disease.

PMID- 29039126
TI  - Brain's neural switch for social dominance in animals.

PMID- 29039127
TI  - Dermotaxis v/s loop suture technique for closure of fasciotomy wounds: a study of
      50 cases.
AB  - Fasciotomy incisions lead to large, unsightly, chronic wounds after surgical
      intervention. Classic management was to use split-thickness skin grafts, but this
      leads to insensate skin with reports that as many as 23% of patients are
      dissatisfied by the appearance of the wound. Since no skin loss has occurred with
      the fasciotomy incision, utilizing the dermal properties of creep, stress
      relaxation and load cycling, closure can be achieved in a better way. We describe
      using dermotaxis for skin edge approximation that is done using inexpensive
      equipment available readily in any standard operating room. Twenty-five patients
      had fasciotomy wounds closed either by dermotaxis or a loop suture technique with
      the inclusion criteria being closed fractures, no concomitant skin loss, fracture
      related compartment syndrome and fasciotomy performed within 36 h. The fasciotomy
      incision was closed in a single stage by loop suture technique or gradually by
      dermotaxis once the oedema had settled between 3 and 5 days. Results were graded
      as excellent if approximation could be achieved, good if sutures had to be
      applied for protective care and poor if wounds needed to be skin-grafted. In the
      dermotaxis group, results were excellent in 15, good in 8 and poor in 2 cases. In
      the loop suture technique group, results were excellent in 20, good in 4 and poor
      in 1 case. Dermal apposition using inexpensive, readily available equipment is an
      alternative method for closure of fasciotomy wounds. If limb oedema has settled
      sufficiently, closure using a loop suture can be done in a single stage. If the
      limb remains oedematous, gradual closure can be done using dermotaxis.

PMID- 29039125
TI  - Hypoxia inducible factor (HIF) in the tumor microenvironment: friend or foe?
AB  - Hypoxia acts as an important regulator of physiological and pathological
      processes. Hypoxia inducible factors (HIFs) are the central players involved in
      the cellular adaptation to hypoxia and are regulated by oxygen sensing EGLN
      prolyl hydroxylases. Hypoxia affects many aspects of cellular growth through both
      redox effects and through the stabilization of HIFs. The HIF isoforms likely have
      differential effects on tumor growth via alteration of metabolism, growth, and
      self-renewal and are likely highly context-dependent. In some tumors such as
      renal cell carcinoma, the EGLN/HIF axis appears to drive tumorigenesis, while in
      many others HIF1 and HIF2 may actually have a tumor suppressive role. An emerging
      role of HIF biology is its effects on the tumor microenvironment. The EGLN/HIF
      axis plays a key role in regulating the function of the various components of the
      tumor microenvironment, which include cancer-associated fibroblasts, endothelial
      cells, immune cells, and the extracellular matrix (ECM). Here, we discuss hypoxia
      and the diverse roles of HIFs in the setting of tumorigenesis and the maintenance
      of the tumor microenvironment as well as possible future directions of the field.

PMID- 29039128
TI  - Distal femoral flexion deformity from growth disturbance treated with a two-level
      osteotomy and internal lengthening nail.
AB  - Salter Harris fractures of the distal femur can lead to growth disturbance with
      resulting leg length inequality and knee deformity. We have looked at a case
      series (3) of patients who presented with a distal femur flexion malunion and
      shortening treated with a distal femoral osteotomy and plating and a proximal
      femoral osteotomy with a magnetic internal lengthening nail. Does a two-level
      osteotomy and internal fixation approach provide a reliable result both
      radiographically and functionally? The average knee extension loss was 12 degrees
      , LLD 47 mm, PDFA 65 degrees , MAD 2 mm. The patients were treated with an acute,
      posterior, opening wedge osteotomy of the distal femur stabilized with a lateral
      plate and screws and grafted with cancellous chips and putty. A second osteotomy
      was made proximally in the femur percutaneously, and the internal lengthening
      nail was inserted. Lengthening was done at approximately 1 mm/day. The average
      extension gain was 12 degrees ; amount of lengthening at the proximal site was 40
      mm, LLD was 3 mm. The average PDFA was 81 degrees , and MAD 3 mm. There were no
      complications. Functional results were excellent. Bone healing index was 24
      days/cm. The average distance from the distal osteotomy to the joint line was 57
      mm. The technique of two-level femur osteotomy stabilized with a plate and
      lengthening nail yielded excellent results with acceptable correction of
      deformity, full knee extension, and improved function. There were no
      complications including implant failure, infection, need for blood transfusion,
      knee stiffness, nonunion, compartment syndrome, or malunion.

PMID- 29039129
TI  - Implicit attitudes and executive control interact to regulate interest in extra
      pair relationships.
AB  - Do we actively maintain monogamous relationships by force of will, or does
      monogamy flow automatically? During functional magnetic resonance imaging (fMRI),
      male participants in a romantic relationship performed the Implicit Association
      Test (IAT) to evaluate implicit attitudes toward adultery and a go/no-go task to
      measure prefrontal activity implicated in explicit executive control.
      Subsequently, they were engaged in a date-rating task in which they rated how
      much they wanted to date unfamiliar females. We found that the individuals with
      higher prefrontal activity during go/no-go task could regulate the interest for
      dates with unattractive females; moreover, the individuals with both a stronger
      negative attitude toward adultery and higher prefrontal activity could regulate
      their interest for dates with attractive females, and such individuals tended to
      maintain longer romantic relationships with a particular partner. These results
      indicate that regulation of amorous temptation via monogamous relationship is
      affected by the combination of automatic and reflective processes.

PMID- 29039131
TI  - Phenotype, disease severity and pain are major determinants of quality of life in
      Fabry disease: results from a large multicenter cohort study.
AB  - Quality of life (QoL) is decreased in patients with Fabry disease (FD). To
      improve QoL, it is important to understand the influence of FD related
      characteristics, symptoms, and complications. In this retrospective cohort study
      we explored the effect of pain (measured by the Brief Pain Inventory), phenotype,
      treatment, and FD-related complications on QoL. QoL data of Fabry patients as
      assessed by the EuroQol five dimension questionnaire (EQ-5D) from two
      international centers of excellence were collected. The aim of this study was to
      evaluate the effect of sex, phenotype, age, different states of disease severity,
      pain, and ERT on EQ-5D utilities. For 286 adult FD patients (mean age 42.5 years,
      40% men, 60% classical phenotype) 2240 EQ-5Ds were available. QoL is decreased in
      men as well as women with FD, especially in older men with a classical phenotype.
      At age 50, utility was lower in men with classical FD compared to those with non
      classical disease (beta = -0.12, 95% CI: -0.23 - 0.01, p = 0.037) with further
      difference in the years thereafter. Cardiovascular complications, stroke or
      transient ischemic attacks, multiple FD-related complications and pain were also
      associated with decreased utilities. Overall, no change in utility was seen in
      patients on ERT over a mean follow-up of 6.1 years. FD leads to a decreased QoL
      compared to the general population. Disease complications and pain both
      negatively influence QoL. Adequate assessment and treatment of pain as well as
      improved strategies to prevent disease complications are needed to improve QoL in
      the FD population.

PMID- 29039130
TI  - Aspirin for Prevention of Preeclampsia.
AB  - Aspirin is currently the most widely prescribed treatment in the prevention of
      cardiovascular complications. The indications for the use of aspirin during
      pregnancy are, however, the subject of much controversy. Since the first evidence
      of the obstetric efficacy of aspirin in 1985, numerous studies have tried to
      determine the effect of low-dose aspirin on the incidence of preeclampsia, with
      very controversial results. Large meta-analyses including individual patient data
      have demonstrated that aspirin is effective in preventing preeclampsia in high
      risk patients, mainly those with a history of preeclampsia. However, guidelines
      regarding the usage of aspirin to prevent preeclampsia differ considerably from
      one country to another. Screening modalities, target population, and aspirin
      dosage are still a matter of debate. In this review, we report the
      pharmacodynamics of aspirin, its main effects according to dosage and gestational
      age, and the evidence-based indications for primary and secondary prevention of
      preeclampsia.

PMID- 29039132
TI  - Violent Injury and Neighborhood Racial/Ethnic Diversity in Oakland, California.
AB  - Racial and ethnic segregation has been linked to a number of deleterious health
      outcomes, including violence. Previous studies of segregation and violence have
      focused on segregation between African Americans and Whites, used homicide as a
      measure of violence, and employed segregation measures that fail to take into
      account neighborhood level processes. We examined the relationship between
      neighborhood diversity and violent injury in Oakland, California. Violent
      injuries from the Alameda County Medical Center Trauma Registry that occurred
      between 1998 and 2002 were geocoded. A local measure of diversity among African
      American, White, Hispanic, and Asian populations that captured interactions
      across census block group boundaries was calculated from 2000 U.S. Census data
      and a Geographic Information System. The relationship between violent injuries
      and neighborhood level of diversity, adjusted for covariates, was analyzed with
      zero-inflated negative binomial regression. There was a significant and inverse
      association between level of racial and ethnic diversity and rate of violent
      injury (IRR 0.30; 95% CI: 0.13-0.69). There was a similar relationship between
      diversity and violent injury for predominantly African American block groups (IRR
      0.23; 95% CI: 0.08-0.62) and predominantly Hispanic block groups (IRR 0.08; 95%
      CI: 0.01-0.76). Diversity was not significantly associated with violent injury in
      predominantly White or Asian block groups. Block group racial and ethnic
      diversity is associated with lower rates of violent injury, particularly for
      predominantly African American and Hispanic block groups.

PMID- 29039133
TI  - The Experience of Implementing Urban HEART Barcelona: a Tool for Action.
AB  - Urban Health Equity Assessment and Response Tool (HEART) is a tool developed by
      the World Health Organization whose objective is to provide evidence on urban
      health inequalities so as to help to decide the best interventions aimed to
      promote urban health equity. The aim of this paper is to describe the experience
      of implementing Urban HEART in Barcelona city, both the adaptation of Urban HEART
      to the city of Barcelona, its use as a means of identifying and monitoring health
      inequalities among city neighbourhoods, and the difficulties and barriers
      encountered throughout the process. Although ASPB public health technicians
      participated in the Urban HEART Advisory Group, had large experience in health
      inequalities analysis and research and showed interest in implementing the tool,
      it was not until 2015, when the city council was governed by a new left-wing
      party for which reducing health inequalities was a priority that Urban HEART
      could be used. A provisional matrix was developed, including both health and
      health determinant indicators, which allowed to show how some neighbourhoods in
      the city systematically fare worse for most of the indicators while others
      systematically fare better. It also allowed to identify 18 neighbourhoods-those
      which fared worse in most indicators-which were considered a priority for
      intervention, which entered the Health in the Barcelona Neighbourhoods programme
      and the Neighbourhoods Plan. This provisional version was reviewed and improved
      by the Urban HEART Barcelona Working Group. Technicians with experience in public
      health and/or in indicator and database management were asked to indicate
      suitability and relevance from a list of potential indicators. The definitive
      Urban HEART Barcelona version included 15 indicators from the five Urban HEART
      domains and improved the previous version in several requirements. Several
      barriers were encountered, such as having to estimate indicators in scarcely
      populated areas or finding adequate indicators for the physical context domain.
      In conclusion, the Urban HEART tool allowed to identify urban inequalities in the
      city of Barcelona and to include health inequalities in the public debate. It
      also allowed to reinforce the community health programme Health in the Barcelona
      Neighbourhoods as well as other city programmes aimed at reducing health
      inequalities. A strong political will is essential to place health inequalities
      in the political agenda and implement policies to tackle them.

PMID- 29039135
TI  - Metabolic iodine and tumours.
AB  - PURPOSE: Purpose of the work is to highlight a possible connection between
      metabolic iodine and natural tumour control. METHOD: Method adopted is to use
      information available in the literature. RESULT: Result indicated a means of the
      purpose being attained. CONCLUSION: Conclusion drawn is that a tumour control
      method derives from the relationship studied.

PMID- 29039136
TI  - Cancer risk management in Tasmanian women with BRCA1 and BRCA2 mutations.
AB  - Women carrying germline mutations in BRCA1 or BRCA2 have significantly increased
      lifetime risks of breast and tubo-ovarian cancer. To manage the breast cancer
      risk women may elect to have breast screening by MRI/mammogram from age 30, to
      take risk-reducing medication, or to have a prophylactic bilateral mastectomy. To
      manage the tubo-ovarian cancer risk, the only effective strategy is to have a
      bilateral salpingo-oophorectomy, recommended by age 40 (BRCA1) or 'around' age 40
      (BRCA2). Early studies suggested that uptake of these cancer risk-reducing
      strategies was low. More recent studies have revealed higher rates of uptake,
      however it is unclear whether uptake is genuinely improving or whether the higher
      uptake rates reflect changes in the populations studied. In this study we
      surveyed 193 BRCA1/2 mutation carriers in the state of Tasmania to determine the
      uptake of cancer risk-reducing strategies and what factors might influence
      women's decisions in relation to both gynaecological and breast surgery. We
      observed that uptake of risk management strategies varied depending on the
      strength of the recommendation in the national guidelines. Uptake rates were >
      90% for strategies which are strongly recommended, such as breast screening by
      MRI/mammogram and bilateral salpingo-oophorectomy, and were unaffected by
      demographic factors such as socio-economic disadvantage and educational
      achievement. Uptake rates were much lower for strategies which are presented in
      the guidelines as options for consideration and where patient choice and shared
      decision making are encouraged, such as prophylactic mastectomy (29%) and
      chemoprevention (1%) and in the case of prophylactic mastectomy, were influenced
      by both socio-economic advantage and educational achievement.

PMID- 29039137
TI  - Three-dimensional image in lung transplantation.
AB  - Three-dimensional computed tomography (3D-CT) technologies have been developed
      and, recently, high-speed and high-quality 3D-CT technologies have been
      introduced to the field of thoracic surgery. The purpose of this manuscript is to
      demonstrate the clinical application of 3D-CT technologies in lung
      transplantation. In Japan, because of the severe donor shortage, living-donor
      lobar lung transplantation (LDLLT) is essential, in addition to cadaveric lung
      transplantation. In LDLLT, size matching is a grave issue, since ideal size
      matching between donor and recipient is usually difficult because of the limited
      population of potential donor. Size matching using pulmonary function test
      results has been widely used as a gold standard, but anatomical size matching
      using 3D-CT volumetry data has also been utilized in LDLLT. In donor lobectomy,
      3D-CT images provided a variety of information regarding anatomical variation of
      pulmonary vessels and bronchial trees preoperatively. These images ensure
      surgical quality and safety, and they also affect surgical procedures for the
      recipient. 3D-CT images are also utilized in various aspects of postoperative
      care, such as detection of chronic lung allograft dysfunction and clarification
      of its subtypes. Furthermore, preoperative 3D-CT simulation is useful in
      developing and performing a special surgical procedure, such as right-to-left
      inverted LDLLT. In conclusion, following the introduction of 3D-CT to the field
      of thoracic surgery, various 3D-CT images and their application to preoperative
      simulations have been introduced in lung transplantation. In the near future,
      this technique will become more prevalent, and frequent use by thoracic surgeons
      will be seen worldwide in daily practice.

PMID- 29039139
TI  - Individualizing the tibial tubercle to trochlear groove distance to patient
      specific anatomy improves sensitivity for recurrent instability.
AB  - PURPOSE: An initial episode of patellar instability poses a treatment challenge
      given the absence of a valid, reproducible, and universally applicable predictor
      of recurrence. Recently, a series of patellar instability ratios (PIRs) were
      described. Each ratio consisted of the traditional tibial tubercle to trochlear
      groove (TT-TG) distance normalized to patient-specific measures. The purpose of
      this study was to investigate the reliability and validity of these novel
      measures. METHODS: Eighty-seven patients experiencing a first-time lateral
      patellar dislocation were identified in a retrospective manner. Magnetic
      resonance imaging (MRI) studies obtained at the time of injury were reviewed. The
      TT-TG distance, patellar width (PW), trochlear width (TW), patellar length (PL),
      and trochlear length (TL) were obtained by two observers in a blinded, randomized
      fashion. Measurement reliability was assessed using intra-class correlation
      coefficients (ICCs). Patients were divided into those having a single dislocation
      (Group 1) and those experiencing recurrent instability (Group 2). The ability of
      the TT-TG distance and each PIR to predict recurrent instability was assessed by
      calculating odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity
      and specificity were also calculated for each measure. RESULTS: Excellent inter
      rater agreement was observed with ICCs > 0.75 for all patellofemoral joint
      measurements obtained on MRI. The TT-TG distance alone was predictive of
      recurrent patellar instability with an OR of 8.9 (p < 0.001). However, the
      isolated TT-TG distance had the lowest sensitivity at 25.6%. Among ratios, a TT
      TG/PL >= 0.5 was the most predictive of recurrent instability with an ORs of 6.1
      (p = < 0.001). A TT-TG/TL >= 0.8 was also predictive of recurrence (OR 4.9, p =
      0.027) and had the highest sensitivity of any measure at 94.9%. CONCLUSION: The
      results of the current study support the reproducibility and predictive ability
      of PIRs. While a TT-TG >= 20 mm was the strongest predictor of recurrent patellar
      instability, it was a relatively insensitive measure. Sensitivity may be improved
      by normalizing the TT-TG distance to patient-specific axial and sagittal plane
      patellofemoral measurements on MRI. Ultimately, PIRs are reproducible measures
      that may serve as an additional tool when clinically assessing the unstable
      patellofemoral joint. LEVEL OF EVIDENCE: III.

PMID- 29039138
TI  - The Role of GABA Receptor Agonists in Anesthesia and Sedation.
AB  - GABA (gamma-aminobutyric acid) receptors, of which there are two types, are
      involved in inhibitory synapses within the central nervous system. The GABAA
      receptor (GABAAR) has a central role in modern anesthesia and sedation practice,
      which is evident from the high proportion of agents that target the GABAAR. Many
      GABAAR agonists are used in anesthesia practice and sedation, including propofol,
      etomidate, methohexital, thiopental, isoflurane, sevoflurane, and desflurane.
      There are advantages and disadvantages to each GABAAR agonist currently in
      clinical use. With increasing knowledge regarding the pharmacology of GABAAR
      agonists, however, newer sedative agents have been developed which employ 'soft
      pharmacology', a term used to describe the pharmacology of agents whereby their
      chemical configuration allows rapid metabolism into inactive metabolites after
      the desired therapeutic effect(s) has occurred. These newer 'soft' GABAAR
      agonists may well approach ideal sedative agents, as they can offer well
      controlled, titratable activity and ultrashort action. This review provides an
      overview of the role that GABAAR agonists currently play in sedation and
      anesthesia, in addition to discussing the future role of novel GABAAR agonists in
      anesthesia and sedation.

PMID- 29039140
TI  - CASQ1 mutations impair calsequestrin polymerization and cause tubular aggregate
      myopathy.

PMID- 29039141
TI  - Does Parkinson's disease start in the gut?
AB  - Parkinson's disease (PD) is pathologically characterized by the presence of
      intraneuronal inclusions, termed Lewy bodies and Lewy neurites, whose main
      component is alpha-synuclein. Based on the topographic distribution of Lewy
      bodies and neurites established after autopsy from PD patients, Braak and
      coworkers hypothesized that PD pathology may start in the gastrointestinal tract
      then spread through the vagus nerve to the brain. This hypothesis has been
      reinforced by the discovery that alpha-synuclein may be capable of spreading
      transcellularly, thereby providing a mechanistic basis for Braak's hypothesis.
      This 'gut to brain' scenario has ignited heated debates within the movement
      disorders community and prompted a large number of studies in both humans and
      animals. Here, we review the arguments for and against the gut as the origin of
      PD. We conclude that the human autopsy evidence does not support the hypothesis
      and that it is too early to draw any definitive conclusions. We discuss how this
      issue might be further addressed in future research.

PMID- 29039142
TI  - Microbiota-Brain-Gut Axis and Neurodegenerative Diseases.
AB  - PURPOSE OF REVIEW: The purposes of this review were as follows: first, to provide
      an overview of the gut microbiota and its interactions with the gut and the
      central nervous system (the microbiota-gut-brain axis) in health, second, to
      review the relevance of this axis to the pathogenesis of neurodegenerative
      diseases, such as Parkinson's disease, and, finally, to assess the potential for
      microbiota-targeted therapies. RECENT FINDINGS: Work on animal models has
      established the microbiota-gut-brain axis as a real phenomenon; to date, the
      evidence for its operation in man has been limited and has been confronted by
      considerable logistical challenges. Animal and translational models have
      incriminated a disturbed gut microbiota in a number of CNS disorders, including
      Parkinson's disease; data from human studies is scanty. While a theoretical basis
      can be developed for the use of microbiota-directed therapies in
      neurodegenerative disorders, support is yet to come from high-quality clinical
      trials. In theory, a role for the microbiota-gut-brain axis is highly plausible;
      clinical confirmation is awaited.

PMID- 29039143
TI  - CD80 Regulates Th17 Cell Differentiation in Coxsackie Virus B3-Induced Acute
      Myocarditis.
AB  - The cluster of differentiation protein complex, CD80/CD86, regulates Th1/Th2
      differentiation in autoimmune disease. In order to establish the effects of
      CD80/CD86 on Th17 cell differentiation in acute viral myocarditis (VMC), we
      infected C57BL/6 mice with Coxsackie virus B3 (CVB3) and examined the effects of
      the treatment with anti-CD80/CD86 monoclonal antibodies (mAbs) on Th17 cell
      differentiation in vivo. The effects of anti-CD80/CD86 mAbs on Th17 cell
      differentiation were further evaluated in vitro. The treatment with anti-CD80 mAb
      induced marked suppression of Th17 cell differentiation and ROR-gammat mRNA
      expression, whereas anti-CD86 mAb alone had no effect, both in vivo and in vitro.
      Our finding that CD80 regulates Th17 differentiation supports the potential
      utility of anti-CD80 mAb as an effective new immunotherapeutic target in acute
      VMC.

PMID- 29039144
TI  - Transoral endoscopic thyroidectomy via a vestibular approach: why and how?
AB  - The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a novel,
      scar-free surgical procedure that does not require visible incisions. Indications
      for TOETVA are as follows: predicted gland width on diagnostic imaging <=10 cm; a
      thyroid volume outline of <45 mL or dominant nodule dimension of <=50 mm; three
      or four Bethesda lesions; a primary papillary microcarcinoma without local or
      distant metastasis; and patient request for optimal esthetic results.
      Contraindications are as follows: patients unfit for general anesthesia;
      precedent radiation in the head, neck, upper mediastinum; antecedent neck
      surgery; recurrent goiter; a gland volume of >45 mL or main nodule diameter of
      >50 mm; and documentation of lymph node or distant metastases,
      tracheal/esophageal infiltration, preoperative laryngeal nerve palsy,
      hyperthyroidism, mediastinal goiter, or an oral abscess. Patients with poorly
      differentiated or un-differentiated cancer, dorsal extrathyroidal radius, and/or
      lateral neck metastasis are not suitable for TOETVA. Following the introduction
      of a robotic surgical system, enabling a three-dimensional surgical view and the
      use of articulating instruments, TOETVA became suitable for most differentiated
      thyroid cancers without evidence of extensive extrathyroidal invasion or lateral
      neck metastasis. The procedure is performed using a vestibular approach and three
      port technique; a 10-mm port is used for the 30 degrees  endoscope, two 5-mm
      ports are used for the dissecting and coagulating instruments, and an 8-mm port
      is placed in the axillary fold during the robotic procedure to enhance fine
      countertraction of tissue for radical oncological dissection. TOETVA follows
      surgical planes and is probably the best scar-free approach to the thyroid, given
      the short distance between the gland and intraoral incisions.

PMID- 29039145
TI  - Adiponectin circulating levels and 10-year (2002-2012) cardiovascular disease
      incidence: the ATTICA Study.
AB  - PURPOSE: Adiponectin is an adipokine with anti-inflammatory and cardiovascular
      protective properties. Existing epidemiological evidence is conflicting on the
      exact relationship between adiponectin and long-term cardiovascular disease (CVD)
      risk. Our aim was to prospectively assess whether circulating adiponectin is
      associated with long-term incident CVD. METHODS: A population-based, prospective
      study in adults (>18 years) without previous CVD history (ATTICA study).
      Circulating total adiponectin levels were measured at baseline (2001-2002) in a
      sub-sample (n = 531; women/men: 222/309; age: 40 +/- 11 years) of the ATTICA
      cohort and complete 10-year follow-up data were available in 366 of these
      participants (women/men: 154/212; age: 40 +/- 12 years). RESULTS: After adjusting
      for multiple factors, including age, sex, body mass index, waist circumference,
      smoking, physical activity, Mediterranean diet adherence, hypertension, diabetes,
      and hypercholesterolemia, our logistic regression analysis indicates that an
      increase in circulating total adiponectin levels by 1 unit was associated with
      36% lower CVD risk (relative risk [RR]: 0.64, 95% confidence interval [CI] 0.42
      0.96; p = 0.03). Further adjusting for interleukin-6 plasma levels had no
      significant impact (RR: 0.60, 95% CI 0.38-0.94; p = 0.03), while additional
      adjustment for circulating C-reactive protein (CRP) modestly attenuated this
      association (RR: 0.63, 95% CI 0.40-0.99; p = 0.046). CONCLUSIONS: In our study,
      elevated circulating total adiponectin levels were associated with lower 10-year
      CVD risk in adults without previous CVD, independently of other established CVD
      risk factors. This association appeared to be modestly attenuated by CRP, yet was
      not mediated by interleukin-6 which is the main endocrine/circulating pro
      inflammatory cytokine.

PMID- 29039146
TI  - Estrogen-based hormone therapy in women with primary ovarian insufficiency: a
      systematic review.
AB  - PURPOSE: Sex hormones play a role in bone density, cardiovascular health, and
      wellbeing throughout reproductive lifespan. Women with primary ovarian
      insufficiency (POI) have lower estrogen levels requiring hormone therapy (HT) to
      manage symptoms and to protect against adverse long-term health outcomes. Yet,
      the effectiveness of HT in preventing adverse outcomes has not been
      systematically assessed. We summarize the evidence regarding effects of HT on
      bone and cardiovascular health in women with POI. METHODS: A comprehensive search
      of the electronic databases MEDLINE, EMBASE, and Scopus was conducted by a
      medical reference librarian from database inception to January 2016. Randomized
      trials and observational cohort studies with an estrogen-based HT intervention in
      women with POI under the age of 40 were included. Reviewers worked independently
      and in duplicate to assess eligibility and risk of bias, and extract data of
      interest from each study. RESULTS: The search identified 1670 articles; 12 met
      inclusion criteria. Four randomized clinical trials and eight cohort studies at
      high risk of bias enrolled 806 women with POI. The most common HT formulations
      were transdermal estradiol and oral conjugated equine estrogen combined with
      medroxyprogesterone acetate. Bone mineral density was the most frequent outcome,
      with three out of eight studies showing HT associated increase benefits. Only one
      study reported effects on fractures or vasomotor symptoms and none on
      cardiovascular mortality. Results regarding lipid profiles were inconsistent.
      CONCLUSIONS: Evidence supporting bone and cardiovascular benefits of HT in women
      with POI is limited by high risk of bias, reliance on surrogate outcomes, and
      heterogeneity of trials regarding the formulation, dose, route of administration,
      and regimen of HT. Further research addressing patient important outcomes such as
      fractures, stroke, and cardiovascular mortality are crucial to optimize benefits
      of this therapy.

PMID- 29039148
TI  - Untargeted Screening of Urinary Peptides Using Offline Nano-Liquid
      Chromatography: MALDI-TOF/TOF Mass Spectrometry.
AB  - In renal transplantation, the discovery of early urine biomarkers of graft
      lesions would be useful in helping physicians to improve patient care and
      minimize the use of invasive techniques such as biopsies. Over the last years,
      high-resolution mass spectrometry has been used extensively for the search of
      biomarkers in various biological fluids. Here we describe a procedure based on
      reverse-phase nano-HPLC, offline plate spotting, and MALDI-TOF and TOF/TOF
      applied in our laboratory for the search of natural peptides in urine samples
      from renal transplant patients.

PMID- 29039147
TI  - Heritability of Addison's disease and prevalence of associated autoimmunity in a
      cohort of 112,100 Swedish twins.
AB  - PURPOSE: The pathophysiology behind autoimmune Addison's disease (AAD) is poorly
      understood, and the relative influence of genetic and environmental factors
      remains unclear. In this study, we examined the heritability of AAD and explored
      disease-associated autoimmune comorbidity among Swedish twins. METHODS: A
      population-based longitudinal cohort of 112,100 Swedish twins was used to
      calculate the heritability of AAD, and to explore co-occurrence of 10 organ
      specific autoimmune disorders in twin pairs with AAD. Diagnoses were collected
      1964-2012 through linkage to the Swedish National Patient Register. The Swedish
      Prescribed Drug Register was used for additional diagnostic precision. When
      available, biobank serum samples were used to ascertain the AAD diagnosis through
      identification of 21-hydroxylase autoantibodies. RESULTS: We identified 29 twins
      with AAD. Five out of nine (5/9) monozygotic pairs and zero out of fifteen (0/15)
      dizygotic pairs were concordant for AAD. The probandwise concordance for
      monozygotic twins was 0.71 (95% CI 0.40-0.90) and the heritability 0.97 (95% CI
      0.88-99). Autoimmune disease patterns of monozygotic twin pairs affected by AAD
      displayed a higher degree of similarity than those of dizygotic twins, with an
      incidence rate ratio of 15 (95% CI 1.8-116) on the number of shared autoimmune
      diagnoses within pairs. CONCLUSIONS: The heritability of AAD appears to be very
      high, emphasizing the need for further research on the genetic etiology of the
      disease. Monozygotic twin concordance for multiple autoimmune manifestations
      suggests strong genetic influence on disease specificity in organ-specific
      autoimmunity.

PMID- 29039149
TI  - Mastalgia and associated factors: a cross-sectional study.
AB  - OBJECTIVES: Mastalgia is a common and painful experience among women. This study
      aimed to determine the prevalence of breast pain, characteristics of the pain,
      and factors associated with breast pain, particularly those that can be changed.
      METHODS: This cross-sectional study comprised women aged from 18 to 65 years. In
      total, 752 women were included. Risk factors for breast pain were determined
      using logistic regression analysis with the entry model, and the risk factors for
      periodic and non-periodic breast pain were assessed using logistic regression
      analysis with the backward model. RESULTS: Results revealed that the following
      were significant risk factors: age between 35 and 50 years (OR, 1.614; CI, 1110
      2347), university graduate (OR, 3.207; CI, 1.874-5.490), BMI of >30 (OR, 2.068;
      CI, 1.163-3.674), excessive use of salt (OR, 1,687; CI, 1.075-2 .647), weight
      gain in the last 5 years (OR, 1.411; CI, 1018-1955), use of a small bra (OR,
      3.260; CI, 2204-4821), and use of a large bra (OR, 1.896; CI, 1276-2817).
      CONCLUSION: Weight control, restriction of salt intake, and selection of a
      suitable brassiere are important for preventing and managing mastalgia.

PMID- 29039150
TI  - Anxiety, depression and coping behaviors with pain in cancer patients who are
      aware or unaware of their cancer.
AB  - OBJECTIVES: This study aimed to investigate whether there are differences in
      depression, anxiety, pain and styles of coping with pain between cancer patients
      with and without awareness of their cancer diagnosis. METHODS: In this study, 30
      cancer patients aware of their diagnosis and 30 cancer patients unaware of their
      diagnosis, all of whom visited a clinic for pain treatment, were enrolled in this
      study. A sociodemographic information form, a questionnaire comprising questions
      about pain severity and related variables, Hospital Anxiety Depression Scale, and
      the Pain Coping Questionnaire were administered to the patients. RESULTS: No
      significant association was observed between the patients with awareness or
      unawareness of cancer with respect to anxiety, depression, pain severity, or
      coping with pain. Pain intensity was significantly associated with depression in
      both the patient groups. CONCLUSION: The study enrolled patients who were
      admitted for pain treatment, and the sampling group was small. However, this is
      the first study to investigate the effects of the awareness of cancer diagnosis
      on pain and its management.

PMID- 29039151
TI  - [Pain experience of nursing students and the methods used to cope with pain].
AB  - OBJECTIVES: This study aimed to determine the pain experience of nursing students
      and the methods used to cope with it. METHODS: This descriptive study was
      conducted at the nursing department. Sampling was not used. The study was
      completed with 264 students. Data were collected using the questionnaire that was
      prepared by the researchers. Descriptive statistics and chi-square test were used
      for data analysis. RESULTS: Of all students, 76.1% (84.1%, females; 56.0%, males)
      who participated in this study had pain. The most experienced pain was headache
      (52.3%), stomachache (42.4%), and low back pain (33%); these were more prevalent
      in females than in males. The use of medication (42.9% in males and 47.8% in
      females) was higher than the other methods for pain treatment. Students who
      stayed in the dormitory were more likely to use drugs (58.5%), whereas those not
      staying in the dormitory were more likely to use non-drug methods (47.4%).
      Students who paid attention to feeding behavior used more medication (80%) than
      who did not pay attention (44.1%; p<0.05). CONCLUSION: Students were mostly
      applied to health institutions owing to pain, they used drugs for headache, and
      the pain affected their daily life activities and resulted in them being absent
      on school days. In conclusion, considering the adverse effects of medications, it
      is recommended that students should be informed regarding reliable traditional
      nonpharmacological methods for coping with pain and should be encouraged to use
      such methods.

PMID- 29039152
TI  - Evaluation of the neuropathic pain in the smokers.
AB  - OBJECTIVES: Nicotine addiction is one of the most important causes of the general
      failure of treatment and keeping the habit of smoking. Peripheral neuropathy is a
      leading factor of smoking. This study aimed to analyze the association of
      neuropathic pain and addiction levels of individuals. METHODS: The study was
      performed on the day on which the smokers visited the hospital for any reason.
      The Douleur Neuropathique 4 (DN-4) Scale and Fagerstrom Addiction Survey were
      administered to the individuals after obtaining their consent. RESULTS: In total,
      444 individuals were included in the study, and 57.2% of them were males (n =
      254). The age average of the individuals with neuropathic pain (46.4+/-12.3
      years) was significantly higher than that of those without pain. The individuals
      with pain smoked approximately 31.8+/-18.3 packet/year cigarettes, whereas those
      without pain smoked approximately 22.4 +/- 15.5 packet/year cigarettes; the
      difference was significant statistically (p<0.05). According to multivariate
      logistic regression analysis with the backward elimination method, the existence
      of pain was found to be PR = 2.22 (95% GA, 1.26-3.91) in terms of sex, DM
      existence was found to be PR = 1.97 (95% GA, 1.02-3.81), and for each standard
      deviation increase (2.7) in Fagerstrom scale, PR was 1.29 (95% GA, 1.14-1.46).
      CONCLUSION: Smoking is a risk factor for neuropathic pain. In our study, the
      possibility of neuropathic pain increases as the duration of smoking and
      addiction level increase, and with diabetes, this rate increases even more. It is
      extremely important that the smokers should be informed regarding these facts and
      possibilities.

PMID- 29039153
TI  - Postoperative analgesia after arthroscopic shoulder surgery: A comparison between
      single-shot interscalene block and single-shot supraclavicular block.
AB  - OBJECTIVES: In arthroscopic rotator cuff surgery for postoperative analgesia
      opioids, nonsteroid analgesics, and local anesthetics can be used. This study
      aimed to compare the effectiveness, additional analgesic requirements, patients
      satisfaction, and complications of single-shot interscalene and supraclavicular
      blocks. METHODS: After obtaining the ethics committee's approval and informed
      consent, 50 ASA I-II patients were randomized to either the interscalene (GISB)
      or supraclavicular (GSCB) group. Preoperatively, patients received an
      ultrasonography-guided block using 30 ml of 0.5% bupivacaine. In the
      postoperative period, morphine patient-controlled analgesia was administered as a
      0.3-mg/h basal dose and 1-mg bolus dose, with a 20-min lockout time.
      Postoperative visual analog scale (VAS; 0-10 cm) scores of the patients were
      evaluated at 4, 8, 12, and 24 h postoperatively; additional analgesic
      requirements, adverse effects, and complications were recorded. Patient
      satisfaction (PS) scores were evaluated after 24 h. RESULTS: VAS scores at 4 h
      were lower in the GSCB group than in the GISB group, and the VAS scores at 8, 12,
      and 24 h were lower in the GISB group than in the GSCB group, with no statistical
      significance. Additional analgesic requirements was 28% in the GISB group and 68%
      in the GSCB group (p < 0.05). Total morphine consumption was lower in the GISB
      group than in the GSCB group (18.95+/-9.2 mg vs. 30.6 +/- 9.6 mg; p < 0.001). PS
      scores were higher in the GISB group than in the GSCB group (7.0+/-1.0 vs. 6.1+/
      0.9; p < 0.01). Adverse effects and complication rates were similar in both the
      groups. In GISB group, seven patients (28%) had nausea/vomiting, whereas in the
      GSCB group, 12 patients (48%) had nausea/vomiting. This difference was
      statistically insignificant. CONCLUSION: Supraclavicular block can be considered
      as an alternative to interscalene block for arthroscopic shoulder surgery.

PMID- 29039154
TI  - Severe headache following ozone therapy: Pneumocephalus.
AB  - Pneumocephalus is defined as air in the cranial cavity. Pneumocephalus can result
      from inadvertent dural puncture during lumbar epidural anesthesia or epidural
      steroid injection. Presently described is case of 41-year-old woman who had
      undergone lumbar disc hernia operation but due to ongoing complaints, was
      diagnosed as having failed back surgery syndrome. Percutaneous epidural
      neuroplasty was performed. In the operating room, under sterile conditions and
      under sedoanalgesia, Racz catheter was inserted in caudal area and guided to
      epidural area with scope. In accordance with Madrid Declaration, 20 ug/mL
      concentration and 5 mL volume oxygen-ozone mixture was injected. After waiting 5
      minutes, 0.25% bupivacaine + 80 mg triamcinolone + 1500 units hyaluronidase was
      administered through the catheter. After epidural neuroplasty procedure, when
      patient was taken to gurney, she complained of severe headache and nausea.
      Computed tomography scans of head were done immediately, and consistent with
      pneumocephalus, air was observed in right lateral ventricle frontal horn,
      interhemispheric fissure, and superior cerebellar cistern. Patient was placed in
      Trendelenburg position and intravenous fluid was replaced. Analgesics and bed
      rest were recommended as treatment. Patient was discharged from hospital on the
      second day. Within a week, headache pain and other complaints had resolved. In
      this article, the case of a failed back surgery patient who was postoperatively
      treated with medical ozone and experienced complication of pneumocephalus is
      discussed in context of literature data.

PMID- 29039155
TI  - Successful anesthetic management in axillo-axillary bypass surgery.
AB  - Axillo-axillary bypass grafting is considered the operation of choice for
      patients with subclavian steal syndrome. Anesthetic management of high-risk
      patients with coronary-subclavian steal syndrome presents safety and technical
      challenges. Presently described is case of chronic obstructive lung disease and
      coronary artery disease in a 52-year-old man who required axillo-axillary bypass
      surgery to treat stenosis at the origin of left subclavian artery. Successful
      anesthetic management was achieved for patient undergoing axillary-axillary
      bypass surgery using a cervical epidural technique.

PMID- 29039156
TI  - [Vertebrobasilar artery dolichoectesia and pain; coincidence or etiology?]
AB  - Dolichoectesia is described as elongation, widening, and tortuosity of an artery.
      Most commonly involved vessels are the intracranial vertebral and basilar
      arteries. Vertebrobasilar artery dolichoectesia is usually asymptomatic. Cerebral
      ischemia, hemorrhage, or compression findings due to mass effect can be seen in
      symptomatic patients. Although there are case reports of trigeminal neuralgia due
      to fifth cranial nerve compression in the literature, to the best of our
      knowledge, neither hemicranial nor continuous facial pain secondary to
      vertebrobasilar artery dolichoectesia has been reported previously. Presently
      described is case of a 42-year-old male with vertebrobasilar dolichoectesia who
      had complaint of continuous right-sided hemicranial pain, and his 19-year-old
      niece, who presented with continuous right-sided facial pain.

PMID- 29039157
TI  - [The anatomical variation to be considered in upper extremity blocks: double
      axillary vein].

PMID- 29039158
TI  - Total spinal block, bupivacaine toxicity or else under epidural anaesthesia?

PMID- 29039159
TI  - Cortisol and migraine: A systematic literature review.
AB  - Migraine is a highly prevalent and disabling disorder. Because stress appears to
      be a prominent trigger of this condition and cortisol is a well-established
      stress hormone, we performed a search on Medline, Scopus, and Web of Science to
      identify clinical studies that assessed cortisol levels in migraineurs. Four
      cross-section studies, one observational study, and three both cross-sectional
      and observational studies were finally included in our analysis. The
      heterogeneity was modest for the sample size (49.8%) but was remarkably high for
      a sample matrix (66.0%), thus precluding the possibility to meta-analyze the
      data. In six of the seven cross-sectional studies, cortisol levels did not differ
      between the cases and controls. With regard to the four observational trials,
      both nitroglycerine and human corticotropin-releasing hormone but not m
      chlorophenylpiperazine were effective in generating a more prominent cortisol
      release in migraineurs than in controls. In a fourth observation trial, salivary
      cortisol did not differ during the migraine attack and during the migraine free
      period. In conclusion, even if altered corticotrope responsiveness exists in
      migraineurs, it appears to be irrelevant in the pathogenesis of migraine.

PMID- 29039160
TI  - Influenza vaccines for preventing acute otitis media in infants and children.
AB  - BACKGROUND: Acute otitis media (AOM) is one of the most common infectious
      diseases in children. It has been reported that 64% of infants have an episode of
      AOM by the age of six months and 86% by one year. Although most cases of AOM are
      due to bacterial infection, it is commonly triggered by a viral infection. In
      most children AOM is self limiting, but it does carry a risk of complications.
      Since antibiotic treatment increases the risk of antibiotic resistance, influenza
      vaccines might be an effective way of reducing this risk by preventing the
      development of AOM. OBJECTIVES: To assess the effectiveness of influenza vaccine
      in reducing the occurrence of acute otitis media in infants and children. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, Embase, CINAHL, LILACS, Web of Science, the WHO International
      Clinical Trials Registry Platform, and ClinicalTrials.gov (15 February 2017). We
      also searched the reference lists of included studies to identify any additional
      trials. SELECTION CRITERIA: Randomised controlled trials comparing influenza
      vaccine with placebo or no treatment in infants and children aged younger than
      six years. We included children of either sex and of any ethnicity, with or
      without a history of recurrent AOM. DATA COLLECTION AND ANALYSIS: Two review
      authors independently screened studies, assessed trial quality, and extracted
      data. We performed statistical analyses using the random-effects and fixed-effect
      models and expressed the results as risk ratio (RR), risk difference (RD), and
      number needed to treat for an additional beneficial outcome (NNTB) for
      dichotomous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: We
      included 11 trials (6 trials in high-income countries and 5 multicentre trials in
      high-, middle-, and low-income countries) involving 17,123 children aged 6 months
      to 6 years. Eight trials recruited participants from a healthcare setting. Ten
      trials (and all four trials that contributed to the primary outcome) declared
      funding from vaccine manufacturers. Four trials reported adequate allocation
      concealment, and 10 trials reported adequate blinding of participants and
      personnel. Attrition was low for eight trials included in the analysis.The
      primary outcome showed a small reduction in at least one episode of AOM over at
      least six months of follow-up (4 trials, 3134 children; RR 0.84, 95% CI 0.69 to
      1.02; RD -0.04, 95% CI -0.08 to -0.00; NNTB 25, 95% CI 12.5 to 100; low-quality
      evidence).The subgroup analyses (i.e. number of courses and types of vaccine
      administered) showed no differences.There was a reduction in the use of
      antibiotics in vaccinated children (2 trials, 1223 children; RR 0.70, 95% CI 0.59
      to 0.83; RD -0.11, 95% CI -0.16 to -0.06; moderate-quality evidence).We were
      unable to demonstrate whether there was any difference in the utilisation of
      health care. The use of influenza vaccine resulted in a significant increase in
      fever (7 trials, 10,615 children; RR 1.15, 95% CI 1.06 to 1.24; RD 0.02, 95% CI
      0.00 to 0.04; low-quality evidence), rhinorrhoea (6 trials, 10,563 children; RR
      1.17, 95% CI 1.07 to 1.29; RD 0.09, 95% CI 0.01 to 0.16; low-quality evidence),
      but no difference in pharyngitis. No major adverse events were reported.Differing
      from the protocol, the original publication of the review included a subgroup
      analysis of AOM episodes by season, and the secondary outcome 'types of influenza
      vaccine' was changed to a subgroup analysis. For this update, we removed the
      subgroup analyses for trial setting, season, and utilisation of health care due
      to the small number of trials involved. We removed Belshe 2000 from primary and
      secondary outcomes (courses of vaccine and types of vaccine) because it reported
      episodes of AOM per person. We did not perform a subgroup analysis by type of
      adverse event. We have reported each type of adverse event as a separate
      analysis. AUTHORS' CONCLUSIONS: Influenza vaccine results in a small reduction in
      AOM. The observed reduction in the use of antibiotics needs to be considered in
      light of current recommended practices aimed at avoiding antibiotic overuse.
      Safety data from these trials were limited. The benefits may not justify the use
      of influenza vaccine without taking into account the vaccine efficacy in reducing
      influenza and safety data. We judged the quality of the evidence to be low to
      moderate. Additional research is needed.

PMID- 29039162
TI  - [Advances on prenatal diagnosis of birth defects associated with genetic
      disorders].
AB  - Birth defects have become a major public health concern in the world, which can
      be resulted from the harmful environmental factors, genetic mutations or their co
      effects. Prenatal diagnosis or preimplantation diagnosis has been considered as
      the only effective way for the prevention of the birth of those defects. Besides
      karyotype analysis and fluorescence in situ hybridization, chromosomal microarray
      analysis and next generation sequencing or its derivatives are in common use.
      This article reviews the advances of the newly emerging molecular techniques in
      prenatal diagnosis of birth defects associated with genetic disorders.

PMID- 29039163
TI  - [Screening for amino acid metabolic disorders of newborns in Zhejiang
      province:prevalence, outcome and follow-up].
AB  - OBJECTIVE: To analyze the result and follow-up data of screening for newborn
      amino acid metabolic disorders in Zhejiang province. METHODS: A total of 1 861
      262 newborns were screened for amino acid metabolic disorders during January 2009
      and December 2016 in Zhejiang province. The screening results and the follow-up
      data were analyzed retrospectively. RESULTS: One hundred and sixty four cases
      were diagnosed as amino acid metabolic disorders with a prevalence of 1:11 349,
      including 83 with hyperphenylalaninaemia (1:22 400), 29 with neonatal
      intrahepatic cholestasis caused by citrin deficiency (1:64 138), 16 with
      methionine S-adenosyltransferase deficiency (1:116 250), 9 with maple syrup urine
      disease (1:206 667), 8 with argininemia (1:232 500), 7 with citrullinemia type I
      (1:265 700), 6 with hyperprolinemia type I (1:310 000), and 2 with
      carbamylphosphate synthetase I deficiency(1:930 000). In addition, ornithine
      transcarbamylase deficiency, cystathionine beta-synthase deficiency,
      argininosucoinate aciduria and tyrosinemia type I were detected in one patient
      for each, respectively. Two patients had developmental delay, 7 patients were
      dead, and 2 cases of maple syrup urine disease were lost to follow-up.
      CONCLUSIONS: Hyperphenylalaninaemia is the most common amino acid metabolic
      disease in newborns in Zhejiang province. Patients with amino acid metabolic
      disorders identified in newborn screening program can have chance for normal
      growth development by intervention.

PMID- 29039164
TI  - [Screening for newborn organic aciduria in Zhejiang province:prevalence, outcome
      and follow-up].
AB  - OBJECTIVE: To analyze the results and follow up data of screening for newborn
      organic aciduria in Zhejiang province. METHODS: The results and follow-up data of
      1 861 262 newborns from Zhejiang province undergoing screening for organic
      aciduria during January 2009 and December 2016 were retrospectively analyzed. The
      acylcarnitine spectrum in urine samples was detected by tandem mass spectrum
      (MS/MS) and the positive patients were confirmed by urine gas chromatography mass
      spectrometry and/or gene analysis. RESULTS: Ninety two cases of organic aciduria
      were confirmed with a prevalence of 1:20 200. Among 40 cases of methylmalonic
      academia (MMA), 13 (32.5%) were of MMA simple type and 27 (67.5%) were combined
      type. Genetic analysis showed 6 cases of MUT type and 1 case of CblB type out of
      7 patients with MMA simple type, 10 cases of CblC and 1 case of CblF out of 11
      patients with combined type, respectively. Six patients had propionic academia
      with a prevalence of 1:310 200, 7 had isovaleric academia (1:265 900), 6 had
      glutaric academia type 1 (1:310 200), 27 had 3-methylcrotonyl-CoA carboxylase
      deficiency (MCC, 1:68 900), 1 had 3-hydroxy-3-methylglutaric aciduria (1:1 861
      300), 2 had beta-ketothiolase deficiency (1:960 600), and 3 had biotinidase
      deficiency/holocarboxylase synthetase deficiency (1:620 400). Thirty-one patients
      had a disease onset at neonatal period, and 15 at post-neonatal period. Thirty
      three patients had brain involvements or cranial imaging disorders. Three
      patients with MMA had kidney diseases or heomlytic uremic syndrome, and 3 had
      myocardial impairments. Twenty patients died during the follow-up. CONCLUSIONS:
      MMA is the most common newborn organic aciduria in Zhejiang province. Except MCC,
      most organic aciduria may lead to metabolism decompensation, complications or
      even death.

PMID- 29039165
TI  - [Screening for fatty acid oxidation disorders of newborns in Zhejiang
      province:prevalence, outcome and follow-up].
AB  - OBJECTIVE: To screen fatty acid oxidation disorders (FAOD) in newborns in
      Zhejiang province. METHODS: A total of 1 861 262 newborns were screened for FAOD
      in Neonatal Screening Center of Zhejiang Province during January 2009 and
      December 2016. The blood samples from newborns were screened by tandem mass
      spectrometry, and diagnosis of FAOD was confirmed by urine organic acid
      measurement combined with genetic analysis. The prognosis and follow-up of
      patients with FAOD were also evaluated. RESULTS: Of 1 861 262 newborns screened,
      121 cases of FAOD were diagnosed. Among 121 cases of FAOD, primary carnitine
      deficiency (PCD) was the most common type (n=78, 64.5%), which was followed by
      short-chain acyl-CoA dehydrogenase deficiency (SCADD, n=27, 22.3%), medium-chain
      acyl-CoA dehydrogenase deficiency (n=5, 4.1%), multiple acyl-CoA dehydrogenase
      deficiency (MADD, n=4, 3.3%), very long-chain acyl-CoA dehydrogenase deficiency
      (n=3, 2.5%), carnitine palmitoyltransferase I deficiency(n=2, 1.7%)and carnitine
      palmitoyltransferase II deficiency (CPTIID, n=2, 1.7%). During 2-82 month follow
      up, 15 patients were lost, 4 were dead (1 PCD, 1 MADD, and 2 CPTIID), and the
      remaining 102 subjects had normal intelligence and physical development without
      any clinical symptoms. CONCLUSIONS: PCD and SCADD are the most common FAODs in
      newborns in Zhejiang province. Most of FAOD patients are asymptomatic, and have
      normal growth and development after early intervention and management.

PMID- 29039166
TI  - [Detection of cell-free fetal DNA in maternal plasma for noninvasive prenatal
      screening of fetal chromosomal aneuploidies in women of advanced maternal age].
AB  - OBJECTIVE: To evaluate the efficiency of cell-free fetal DNA detection as a non
      invasive prenatal screening (NIPS) method for women of advanced maternal age.
      METHODS: A total of 10 584 women of advanced maternal age who received NIPS were
      recruited from the Women's Hospital, Zhejiang University School of Medicine and
      Jiaxing Maternal and Child Health Hospital during February 2015 and September
      2016. The pregnancy outcome was followed-up. The sensitivity, specificity,
      positive and negative predictive value of fetal chromosomal aneuploidy detected
      in NIPS were analyzed. And the relationship between maternal age and fetal common
      chromosomal aneuploidy was analyzed. RESULTS: The sensitivity, specificity,
      positive and negative predictive value of NIPS were 100.00%, 99.96%, 91.67%,
      100.00% for trisomy 21, 100.00%, 99.93%, 68.18%, 100.00% for trisomy 18, and
      100.00%, 99.97%, 25.00%, 100.00% for trisomy 13. High-risk rate and true positive
      rate of trisomy 21 were positively correlated with the maternal age (all P<0.01).
      There were significant differences in high-risk rate and true positive rate
      between 35-37 year old groups and 38-40 year old groups (all P<0.05). Such
      difference was also found in high-risk rate between 38-40 year old group and >=
      41 year old group (P<0.05), but not in true positive rate between two groups
      (P>0.05). CONCLUSIONS: NIPS is effective for fetal chromosomal aneuploidy
      screening in women of advanced maternal age. For women under 38 years of age,
      NIPS is preferred; for women of 41 and above, invasive diagnostic methods are
      suggested; and for women between 38-41 years old, the option can be determined by
      themselves after risks and advantages were fully informed.

PMID- 29039167
TI  - [Single nucleotide polymorphism-array in genetic analysis of chorionic villi from
      early spontaneous miscarriages].
AB  - OBJECTIVE: To assess the clinical application of single nucleotide polymorphism
      (SNP)-array in detecting abnormal chromosome karyotypes of chorionic villi from
      early spontaneous abortuses. METHODS: A total of 861 chorionic villus samples
      from unexplained early spontaneous abortion were collected from Women's Hospital,
      Zhejiang University School of Medicine during October 2013 and June 2016, and SNP
      array was performed to detect genome-wide DNA copy number variants. RESULTS: All
      samples were successfully tested by SNP-array and 440 cases (51.10%) were found
      to have abnormal chromosome constitutions. Aneuploidy was identified in 358
      (41.58%) cases, distributing in all chromosomes except chromosome 1. Triploidy
      and haploidy were found in 21 (2.44%) and one case (0.12%), respectively. Thirty
      seven cases (4.30%) were identified as single chromosomal segment deletion or
      duplication, 25 of which were less than 10 Mb in size. For 6 of 25 cases with
      unclear pathogenesis, family studies were carried out to identify origin of
      deletion or duplication, showing that 4 cases were de novo and 2 were inherited
      from one of the parents. Twenty-three cases (2.67%) showed two chromosomal
      deletion/duplication segments. Combining with karyotyping and fluorescence in
      situ hybridization, 6 cases were identified as de novo aberration and 11 carried
      small-size segmental balanced abnormality. CONCLUSIONS: SNP-array can provide a
      relatively comprehensive genetic analysis of chorionic villi and can detect
      various kinds of chromosome abnormalities in spontaneous miscarriages.

PMID- 29039168
TI  - [Maternal serum alpha fetoprotein and free beta-hCG of second trimester for
      screening of fetal gastroschisis and omphalocele].
AB  - OBJECTIVE: To assess the detection of maternal serum alpha fetoprotein (MSAFP)
      and free beta-HCG levels of second trimester for screening of fetal gastroschisis
      and omphalocele. METHODS: Clinical data of 622 639 pregnant women from 5 prenatal
      screening centers in Hangzhou during October 2007 and September 2016 were
      analyzed retrospectively. Thirty cases of gastroschisis and 30 cases of
      omphalocele diagnosed by ultrasonography and postmortem findings were enrolled in
      the study and 116 cases of pregnant women with normal fetal development during
      the same period were selected as control group. The cut-off value and area under
      ROC curve (AUC) of MSAFP and free beta-hCG for diagnosis of fetal gastroschisis
      and omphalocel were analyzed. RESULTS: MSAFP levels of women with fetal
      gastroschisis and omphalocele were 4.41 (0.88-11.69) MOM and 2.31 (0.72-23.20)
      MOM, which were significantly higher than that of control group[0.98 (0.41-2.26)
      MOM, all P<0.01]. Free beta-hCG level of women with fetal gastroschisis was 1.25
      (0.35-19.94) MOM, which was significantly higher than that of control group[0.86
      (0.17-6.11) MOM, P<0.05). But there were no significant difference in free beta
      hCG between fetal omphalocele group[1.03(0.21-8.95)]and control group (P>0.05).
      The AUCs of MSAFP for diagnosis of gastroschisis and omphalocele were 0.897 (95%
      CI:0.822-0.972) and 0.852(95% CI:0.762-0.942), respectively (all P<0.01). Taking
      1.655 MOM as the cut-off value of MSAFP for abdominal wall defects (gastroschisis
      and omphalocele), the sensitivity was 68.30%, specificity was 99.60% and Youden
      index was 0.649. CONCLUSIONS: MSAFP of second trimester is a better biomarker
      than free beta-hCG in screening abdominal wall defects.

PMID- 29039169
TI  - [Prenatal diagnosis of Joubert syndrome:one case report and literature review].
AB  - A 25-year-old nulliparity underwent prenatal ultrasonography, and the fetal
      cerebellar abnormality was suspected. The fetal MRI showed 'molar tooth sign' in
      midbrain and cerebellar vermis hypoplasia. The fetal cerebellar vermis hypoplasia
      was confirmed by MRI imaging and autopsy after induced abortion. The next
      generation sequencing showed that the fetus had a heterozygous mutation of CC2D2A
      gene (c.2728C > T and c.4598T > C), which might be the cause of the disease.

PMID- 29039170
TI  - [Research progress on the safety of offsprings conceived by assisted reproductive
      technology].
AB  - Assisted reproductive technology (ART) employs superovulation, in vitro culture
      and other micromanipulation to complete oocyte maturation, fertilization and
      early embryo development. Although these techniques have been successfully
      applied to solve infertility problems, the process may interfere in cell
      proliferation, differentiation and growth. The clinical and laboratory studies on
      the safety issue of ART are reviewed in this article. Studies found that the
      incidence of birth defects increased in ART offspring. Superovulation, in vitro
      culture and intracytoplasmic sperm injection may induce epigenetic aberrations
      during embryo development, which would influence the development of ART conceived
      children. The epigenetic susceptibility related to ART might be transmitted to
      subsequent generations, and the potential impact on ART offspring still need
      further investigation. In addition, ART treatments may also increase the risk of
      genetic diseases.

PMID- 29039171
TI  - [Correlation of fetuin-B concentrations in serum and follicular fluid with
      outcomes of in vitro fertilization].
AB  - OBJECTIVE: To investigate the relationship between serum/follicular fluid fetuin
      B levels and outcome of in vitro fertilization (IVF). METHODS: Infertility women
      (28 with low fertilization rates, 44 with normal fertilization rates) receiving
      IVF in Women's Hospital of Zhejiang University School of Medicine during June and
      December 2016 were enrolled in the study. Serum/follicular fluid fetuin B levels
      were measured with ELISA method. Correlations of serum and follicular fetuin B
      level with fertilization outcome of IVF were analyzed with Pearson correlation
      coefficient and receiver operating characteristic (ROC) curve. RESULTS: A
      positive correlation between serum fetuin B and follicular fluid fetuin B levels
      was observed (r=0.675, P<0.01). Both serum and follicular fluid fetuin B levels
      in women with low fertilization rates of IVF were lower than those in women with
      normal fertilization rates[(6.09+/-1.31) MUg/mL vs. (7.13+/-1.47) MUg/mL,
      t=3.050, P<0.05; (5.13+/-0.96)MUg/mL vs. (6.22+/-1.33) MUg/mL, t=3.755, P<0.01].
      ROC analysis showed that the area under curve (AUC) of serum fetuin B level in
      predicting fertilization rate was 0.832 (95% CI:0.729-0.934, P<0.01), and 6.08
      MUg/mL could be used as cut-off value. CONCLUSIONS: Serum fetuin B level is
      correlated with follicular fluid fetuin B level, and it may be used for
      predicting the fertilization outcome of IVF.

PMID- 29039172
TI  - [Effect of oxygen concentration on outcome of in-vitro fertilization-embryo
      transfer].
AB  - OBJECTIVE: To investigate the effect of low and high oxygen concentration on
      embryo development, pregnancy outcome and birth defects of in vitro fertilization
      embryo transfer (IVF-ET). METHODS: According to the oxygen concentration of in
      vitro culture environment, the IVF-ET performed in the Women's Hospital, Zhejiang
      University School of Medicine during 2013 and 2015 were divided into low oxygen
      concentration group (n=2036, 5% O2) and high oxygen concentration group (n=4617,
      20% O2). The rate of fertilization, good quality embryo, clinical pregnancy,
      ectopic pregnancy, abortion and birth defect were compared between two groups.
      RESULTS: The good quality embryo rate was significantly higher in the low oxygen
      concentration group (P<0.05). However, no significant differences were found
      between two groups in the rate of fertilization, clinical pregnancy, ectopic
      pregnancy, abortion and birth defect (all P>0.05). CONCLUSIONS: Low oxygen
      environment may improve the potential of embryonic development, but its impact on
      pregnancy outcome and birth defect is not significant.

PMID- 29039173
TI  - [Effects of embryo cryopreservation and thawing on clinical outcomes of
      transplantable embryos after cleavage-stage preimplantation genetic diagnosis or
      screening].
AB  - OBJECTIVE: To investigate the effects of embryo cryopreservation and thawing on
      clinical outcomes of transplantable embryos after preimplantation genetic
      diagnosis (PGD) or preimplantation genetic screening (PGS) in cleavage-stage.
      METHODS: The clinical data of 302 cases (including 118 cases using frozen/thawing
      embryos and 184 cases using fresh embryos) undergoing PGD/PGS in Women's
      Hospital, Zhejiang University School of Medicine during January 2011 and December
      2016 were retrospectively analyzed. The pregnancy rate, implantation rate, live
      birth rate and abortion rate of fresh and frozen-thawed embryo transfer (FET)
      cycles were compared. And the influencing factors for pregnancy outcome was
      analyzed by multivariate logistic regression. RESULTS: The rate of normal or
      balanced translocation embryos in fresh cycle was higher than that in FET cycle
      (23.52% vs 16.67%, P<0.05), and the average number of transplanted embryos was
      more than that in FET cycle (1.54+/-0.56 vs 1.33+/-0.51, P<0.05). But there were
      no significant differences in pregnancy rate (36.42% vs 40.00%, P>0.05),
      implantation rate (26.62% vs 32.91%, P>0.05), abortion rate (19.44% vs 8.33%,
      P>0.05) and live birth rate (25.96% vs 28.33%, P>0.05) between fresh cycle and
      FET cycle. Multivariate logistic regression showed that, parent ages, embryo
      status (fresh or frozen), the mode of PGD/PGS and the findings of PGD/PGS had no
      impact on pregnancy outcome (all P>0.05). CONCLUSIONS: Cryopreservation do not
      have significant effects on the clinical outcomes of transplantable embryos after
      PGD/PGS in cleavage-stage.

PMID- 29039174
TI  - [Long-term effects of polycystic ovary syndrome on the offspring].
AB  - Polycystic ovary syndrome (PCOS) is an endocrine disorder with reproductive
      dysfunction and abnormal metabolic syndrome. However, its etiology is unknown
      yet. Androgen hypersecretion is one of the main features of PCOS. It has been
      found that PCOS has various effects on the offspring in reproductive, metabolic
      and nervous systems, including:increasing secretion of gonadotropin-releasing
      hormone and luteinizing hormone, ovarian morphological changes and abnormal
      secretion of sex hormones, leading to disorders of lipid and glucose metabolism,
      and increasing the risks of depression and autism. However, there is still lack
      of direct evidence, and more studies should be conducted on the underlying
      mechanism in future.

PMID- 29039175
TI  - [Comparison of limus-eluting stent with paclitaxel-eluting stent for patients
      with coronary small vessel disease:a systematic review and meta-analysis].
AB  - OBJECTIVE: To compare the efficacy of limus-eluting stent (LES) with paclitaxel
      eluting stent (PES) for patients with coronary small vessel disease. METHODS: The
      studies of LES and PES used for patients with coronary small vessel disease were
      searched in PubMed, Web of Science, ClinicalTrials, SinoMed, CNKI, Wanfang data
      and CQVIP. The relative risk (RR) estimates with 95% confidence intervals and
      other statistical variables were calculated with Stata 14.0, and the meta
      analysis was performed with RevMan 5.2. RESULTS: Eight studies involving 4738
      patients were included in the meta-analysis. Compared with PES, LES implantation
      was associated with significant reduction in major adverse cardiovascular events
      (RR=0.64, 95% CI:0.53-0.77, Z=4.59, P<0.01), myocardial infarction (RR=0.61, 95%
      CI:0.45-0.82; Z=3.24, P<0.01), stent thrombosis (RR=0.22, 95% CI:0.13-0.37,
      Z=5.71, P<0.01), and target lesion revascularization (RR=0.56, 95% CI:0.44-0.71,
      Z=4.72, P<0.01), while no difference was observed in cardiac death (RR=1.08, 95%
      CI:0.62-1.88, Z=0.26, P>0.05) and target vessel revascularization(RR=0.80, 95%
      CI:0.45-1.44, Z=0.74, P>0.05). CONCLUSIONS: LES has better efficacy than PES for
      patients with coronary small vessel disease, which may be the preferred stents
      for these patients.

PMID- 29039176
TI  - [Research progress on the relationship of brown adipose tissue with polycystic
      ovary syndrome].
AB  - Brown adipose tissue (BAT) holds great promise for the prevention and treatment
      of metabolism diseases through thermoregulation. Polycystic ovary syndrome (PCOS)
      is a complex condition with anovulation, hyperandrogenism, and polycystic
      ovaries, and also manifests glucolipid metabolic disorders. Recent researches
      have shown that transplantation of BAT into a PCOS rat could significantly
      alleviate the phenotypes. This article reviews the role of BAT in pathogenesis of
      PCOS, which may provide information for prevention and treatment of PCOS.

PMID- 29039177
TI  - [The involvement of galectin-1 in implantation and pregnancy maintenance at the
      maternal-fetal interface].
AB  - As a member of galectins family, galectin-1(Gal-1)is widely expressed in tissues
      and cells, and participates in a variety of physiological and pathological
      processes, such as cell adhesion, proliferation, apoptosis and inflammatory
      reaction. Recently, it has been found that Gal-1 is highly expressed at the
      maternal-fetal interface and plays important roles in trophoblast cell
      proliferation, differentiation and invasion, endometrial receptivity, placental
      angiogenesis and maternal-fetal immune tolerance. In this review, we outline the
      expression of Gal-1 at the maternal-fetal interface and the involvement of Gal-1
      in embryo implantation and pregnancy maintenance, to provide novel insights for
      the early diagnosis, prognostic assessment and treatment of early pregnancy loss
      and pregnancy-related diseases.

PMID- 29039178
TI  - [Potential clinical application of Kisspeptin in reproductive endocrinology].
AB  - Gonadotropin-releasing hormone (GnRH) plays an important role in the process of
      reproduction. Studies have shown that a family of peptides Kisspeptin can act on
      GnRH-related neurons, stimulating the secretion of GnRH, and activating the
      hypothalamic-pituitary-gonadal axis. Both animal experiments and clinical studies
      have shown that exogenous administration of Kisspeptin is able to induce
      physiological GnRH release in healthy individuals and those with endocrine
      disorders, which brings great hope for treatment of reproductive endocrine
      diseases. The effect of Kisspeptin is similar to the physiological process in
      induction of ovulation and ovum maturation, leading to high security and
      efficiency for women receiving in vitro fertilization. Kisspeptin is involved in
      trophoblast invasion, so it may be useful for predicting pregnancy outcomes. In
      addition, Kisspeptin is the key hormone in the onset of puberty acting as a
      signal transducer in metabolism and reproduction, so it provides some directions
      for studies of polycystic ovary syndrome, hyperprolactinemia, and other metabolic
      related reproductive endocrine diseases. This article reviews the character of
      Kisspeptin and the prospect of its application in treatment of reproductive
      endocrine diseases.

PMID- 29039179
TI  - [Advances in the application of high-throughput sequencing in clinical genetics].

PMID- 29039180
TI  - Heart Failure and Long-Term Survival Among Older Women With Breast Cancer
AB  - Objectives: To evaluate the association between heart failure and overall
      survival up to 10 years after breast cancer diagnosis. Sample & Setting: Women
      aged 65 years or older diagnosed with invasive breast cancer, with and without
      self-reported heart failure, were examined for this retrospective cohort study
      using Surveillance, Epidemiology, and End Results cancer registries in the United
      States. Methods & Variables: Cox proportional hazards regression was used to
      examine the association between heart failure status and mortality, adjusting for
      comorbidity and other clinical or sociodemographic differences. Associations were
      examined overall and stratified by cancer stage. Results: In adjusted models,
      having heart failure was associated with increased likelihood of death up to 10
      years after cancer diagnosis. In adjusted subanalyses by cancer stage, heart
      failure was associated with increased likelihood of death up to 10 years after
      cancer diagnosis in women with stage I or II cancer but not in women with stage
      III/IV cancer. Implications for Nursing: Although early-stage breast cancer is
      generally associated with better prognosis, the competing mortality risk of heart
      failure was greater for this group than for women with advanced cancer.
      Prevention and management of cardiovascular disease should be prioritized for
      this patient subgroup.

PMID- 29039181
TI  - Comparisons of Airborne Measurements and Inventory Estimates of Methane Emissions
      in the Alberta Upstream Oil and Gas Sector.
AB  - Airborne measurements of methane emissions from oil and gas infrastructure were
      completed over two regions of Alberta, Canada. These top-down measurements were
      directly compared with region-specific bottom-up inventories that utilized
      current industry-reported flaring and venting volumes (reported data) and
      quantitative estimates of unreported venting and fugitive sources. For the 50 *
      50 km measurement region near Red Deer, characterized by natural gas and light
      oil production, measured methane fluxes were more than 17 times greater than that
      derived from directly reported data but consistent with our region-specific
      bottom-up inventory-based estimate. For the 60 * 60 km measurement region near
      Lloydminster, characterized by significant cold heavy oil production with sand
      (CHOPS), airborne measured methane fluxes were five times greater than directly
      reported emissions from venting and flaring and four times greater than our
      region-specific bottom up inventory-based estimate. Extended across Alberta, our
      results suggest that reported venting emissions in Alberta should be 2.5 +/- 0.5
      times higher, and total methane emissions from the upstream oil and gas sector
      (excluding mined oil sands) are likely at least 25-50% greater than current
      government estimates. Successful mitigation efforts in the Red Deer region will
      need to focus on the >90% of methane emissions currently unmeasured or
      unreported.

PMID- 29039182
TI  - Chiral Nanographene Propeller Embedding Six Enantiomerically Stable [5]Helicene
      Units.
AB  - A one-step synthesis of a nanographene propeller with a D3-symmetry was obtained
      starting from 7,8-dibromo[5]helicene by Yamamoto nickel(0) couplings. It afforded
      a chiral polyaromatic hydrocarbon (PAH) embedding six enantiomerically stable
      [5]helicene units. This dense accumulation of helical strain resulted in a
      distorted geometry, but stable stereochemistry. The conformational, structural,
      chiroptical, and photophysical properties of the molecule are reported.

PMID- 29039183
TI  - Electrochemically Generated cis-Carboxylato-Coordinated Iron(IV) Oxo Acid-Base
      Congeners as Promiscuous Oxidants of Water Pollutants.
AB  - The nonheme iron(IV) oxo complex [FeIV(O)(tpenaH)]2+ and its conjugate base
      [FeIV(O)(tpena)]+ [tpena- = N,N,N'-tris(2-pyridylmethyl)ethylenediamine-N'
      acetate] have been prepared electrochemically in water by bulk electrolysis of
      solutions prepared from [FeIII2(MU-O)(tpenaH)2](ClO4)4 at potentials over 1.3 V
      (vs NHE) using inexpensive and commercially available carbon-based electrodes.
      Once generated, these iron(IV) oxo complexes persist at room temperature for
      minutes to half an hour over a wide range of pH values. They are capable of
      rapidly decomposing aliphatic and aromatic alcohols, alkanes, formic acid,
      phenols, and the xanthene dye rhodamine B. The oxidation of formic acid to carbon
      dioxide demonstrates the capacity for total mineralization of organic compounds.
      A radical hydrogen-atom-abstraction mechanism is proposed with a reactivity
      profile for the series that is reminiscent of oxidations by the hydroxyl radical.
      Facile regeneration of [FeIV(O)(tpenaH)]2+/ [FeIV(O)(tpena)]+ and catalytic
      turnover in the oxidation of cyclohexanol under continuous electrolysis
      demonstrates the potential of the application of [FeIII(tpena)]2+ as an
      electrocatalyst. The promiscuity of the electrochemically generated iron(IV) oxo
      complexes, in terms of the broad range of substrates examined, represents an
      important step toward the goal of cost-effective electrocatalytic water
      purification.

PMID- 29039184
TI  - Single Walled Carbon Nanotube Based Air Pocket Encapsulated Ultraviolet Sensor.
AB  - Carbon nanotube (CNT) is a promising candidate as a sensor material for the
      sensitive detection of gases/vapors, biomarkers, and even some radiation, as all
      these external variables affect the resistance and other properties of nanotubes,
      which forms the basis for sensing. Ultraviolet (UV) radiation does not impact the
      nanotube properties given the substantial mismatch of bandgaps and therefore,
      CNTs have never been considered for UV sensing, unlike the popular ZnO and other
      oxide nanwires. It is well-known that UV assists the adsorption/desorption
      characteristics of oxygen on carbon nanotubes, which changes the nanotube
      resistance. Here, we demonstrate a novel sensor structure encapsulated with an
      air pocket, where the confined air is responsible for the UV sensing mechanism
      and assures sensor stability and repeatability over time. In addition to the
      protection from any contamination, the air pocket encapsulated sensor offers
      negligible baseline drift and fast recovery compared to previously reported
      sensors. The air pocket isolated from the outside environment can act as a
      stationary oxygen reservoir, resulting in consistent sensor characteristics.
      Furthermore, this sensor can be used even in liquid environments.

PMID- 29039185
TI  - Fabrication of Lanthanum Strontium Cobalt Ferrite-Gadolinium-Doped Ceria
      Composite Cathodes Using a Low-Price Inkjet Printer.
AB  - In this work, we have successfully fabricated lanthanum strontium cobalt ferrite
      (LSCF)-gadolinium-doped ceria (GDC) composite cathodes by inkjet printing and
      demonstrated their functioning in solid oxide fuel cells (SOFCs). The cathodes
      are printed using a low-cost HP inkjet printer, and the LSCF and GDC source inks
      are synthesized with fluidic properties optimum for inkjet printing. The
      composition and microstructure of the LSCF and GDC layers are successfully
      controlled by controlling the color level in the printed images and the number of
      printing cycles, respectively. Anode-support type SOFCs with optimized LSCF-GDC
      composite cathodes synthesized by our inkjet printing method have achieved a
      power output of over 570 mW cm-2 at 650  degrees C, which is comparable to the
      performance of a commercial SOFC stack. Electrochemical impedance analysis is
      carried out to establish a relationship between the cell performance and the
      compositional and structural characteristics of the printed LSCF-GDC composite
      cathodes.

PMID- 29039186
TI  - Liquid-Solid Dual-Gate Organic Transistors with Tunable Threshold Voltage for
      Cell Sensing.
AB  - Liquid electrolyte-gated organic field effect transistors and organic
      electrochemical transistors have recently emerged as powerful technology
      platforms for sensing and simulation of living cells and organisms. For such
      applications, the transistors are operated at a gate voltage around or below 0.3
      V because prolonged application of a higher voltage bias can lead to membrane
      rupturing and cell death. This constraint often prevents the operation of the
      transistors at their maximum transconductance or most sensitive regime. Here, we
      exploit a solid-liquid dual-gate organic transistor structure, where the
      threshold voltage of the liquid-gated conduction channel is controlled by an
      additional gate that is separated from the channel by a metal-oxide gate
      dielectric. With this design, the threshold voltage of the "sensing channel" can
      be linearly tuned in a voltage window exceeding 0.4 V. We have demonstrated that
      the dual-gate structure enables a much better sensor response to the detachment
      of human mesenchymal stem cells. In general, the capability of tuning the optimal
      sensing bias will not only improve the device performance but also broaden the
      material selection for cell-based organic bioelectronics.

PMID- 29039187
TI  - Abiotic Conversion of Extracellular NH2OH Contributes to N2O Emission during
      Ammonia Oxidation.
AB  - Abiotic processes involving the reactive ammonia-oxidation intermediates nitric
      oxide (NO) or hydroxylamine (NH2OH) for N2O production have been indicated
      recently. The latter process would require the availability of substantial
      amounts of free NH2OH for chemical reactions during ammonia (NH3) oxidation, but
      little is known about extracellular NH2OH formation by the different clades of
      ammonia-oxidizing microbes. Here we determined extracellular NH2OH concentrations
      in culture media of several ammonia-oxidizing bacteria (AOB) and archaea (AOA),
      as well as one complete ammonia oxidizer (comammox) enrichment (Ca. Nitrospira
      inopinata) during incubation under standard cultivation conditions. NH2OH was
      measurable in the incubation media of Nitrosomonas europaea, Nitrosospira
      multiformis, Nitrososphaera gargensis, and Ca. Nitrosotenuis uzonensis, but not
      in media of the other tested AOB and AOA. NH2OH was also formed by the comammox
      enrichment during NH3 oxidation. This enrichment exhibited the largest
      NH2OH:final product ratio (1.92%), followed by N. multiformis (0.56%) and N.
      gargensis (0.46%). The maximum proportions of NH4+ converted to N2O via
      extracellular NH2OH during incubation, estimated on the basis of NH2OH abiotic
      conversion rates, were 0.12%, 0.08%, and 0.14% for AOB, AOA, and Ca. Nitrospira
      inopinata, respectively, and were consistent with published NH4+:N2O conversion
      ratios for AOB and AOA.

PMID- 29039188
TI  - Updated Polychlorinated Biphenyl Mass Budget for Lake Michigan.
AB  - This study revisits and updates the Lake Michigan Mass Balance Project (LMMBP)
      for polychlorinated biphenyls (PCBs) that was conducted in 1994-1995. This work
      uses recent concentrations of PCBs in tributary and open lake water, air, and
      sediment to calculate an updated mass budget. Five of the 11 LMMBP tributaries
      were revisited in 2015. In these five tributaries, the geometric mean
      concentrations of ?PCBs (sum of 85 congeners) ranged from 1.52 to 22.4 ng L-1.
      The highest concentrations of PCBs were generally found in the Lower Fox River
      and in the Indiana Harbor and Ship Canal. The input flows of ?PCBs from wet
      deposition, dry deposition, tributary loading, and air to water exchange, and the
      output flows due to sediment burial, volatilization from water to air, and
      transport to Lake Huron and through the Chicago Diversion were calculated, as
      well as flows related to the internal processes of settling, resuspension, and
      sediment-water diffusion. The net transfer of ?PCBs is 1240 +/- 531 kg yr-1 out
      of the lake. This net transfer is 46% lower than that estimated in 1994-1995. PCB
      concentrations in most matrices in the lake are decreasing, which drove the
      decline of all the individual input and output flows. Atmospheric deposition has
      become negligible, while volatilization from the water surface is still a major
      route of loss, releasing PCBs from the lake into the air. Large masses of PCBs
      remain in the water column and surface sediments and are likely to contribute to
      the future efflux of PCBs from the lake to the air.

PMID- 29039189
TI  - Composing RNA Nanostructures from a Syntax of RNA Structural Modules.
AB  - Natural stable RNAs fold and assemble into complex three-dimensional
      architectures by relying on the hierarchical formation of intricate, recurrent
      networks of noncovalent tertiary interactions. These sequence-dependent networks
      specify RNA structural modules enabling orientational and topological control of
      helical struts to form larger self-folding domains. Borrowing concepts from
      linguistics, we defined an extended structural syntax of RNA modules for
      programming RNA strands to assemble into complex, responsive nanostructures under
      both thermodynamic and kinetic control. Based on this syntax, various RNA
      building blocks promote the multimolecular assembly of objects with well-defined
      three-dimensional shapes as well as the isothermal folding of long RNAs into
      complex single-stranded nanostructures during transcription. This work offers a
      glimpse of the limitless potential of RNA as an informational medium for
      designing programmable and functional nanomaterials useful for synthetic biology,
      nanomedicine, and nanotechnology.

PMID- 29039190
TI  - Palladium-Catalyzed Diastereoselective Synthesis of 3-Arylbutanoic Acid
      Derivatives.
AB  - The first palladium-catalyzed diastereoselective conjugate addition of
      arylboronic acids to chiral imides is reported. The catalytic system employing 4
      tert-butyloxazolidin-2-one as the chiral auxiliary in a mixed solvent system of
      MeOH/H2O (1:3) under an air atmosphere provides the optically active 3
      arylbutanoic acid derivatives in excellent yields with high diastereoselectivity.

PMID- 29039191
TI  - Separation of 300 and 100 nm Particles in Fabry-Perot Acoustofluidic Resonators.
AB  - Separation of particles on the order of 100 nm with acoustophoresis has been
      challenging to date because of the competing natures of the acoustic radiation
      force and acoustic streaming on the particles. In this work, we present a surface
      acoustic wave (SAW)-based device that integrates a Fabry-Perot type acoustic
      resonator into a microfluidic channel to separate submicrometer particles. This
      configuration enhances the overall acoustic radiation force on the particles and
      thereby offers controlled manipulation of particles as small as 300 nm.
      Additionally, SAW-based excitation generates high-frequency acoustic waves in the
      system relative to bulk acoustic wave (BAW)-based actuation, which suppresses
      Rayleigh streaming effects on the submicrometer particles. We demonstrate a
      continuous-flow acoustophoretic separation of 300 and 100 nm particles in our
      device with a separation efficiency of 86.3%. We also present an analytical
      stochastic method to model the transport of submicrometer particles in the device
      and predict the migration trajectories as a function of acoustic and velocity
      potential field strengths. Our model incorporates particle diffusion, which is
      important for small particles, and successfully predicts the size-dependent
      separation modality of our system. This device can be used for several
      applications in microfluidics that require sorting of the submicrometer
      particles, and the analytical method can also be extended to predict the particle
      transport in other systems.

PMID- 29039192
TI  - Changes in Glucose Fermentation Pathways as a Response to the Free Ammonia
      Concentration in Microbial Electrolysis Cells.
AB  - When a mixed-culture microbial electrolysis cell (MEC) is fed with a fermentable
      substrate, such as glucose, a significant fraction of the substrate's electrons
      ends up as methane (CH4) through hydrogenotrophic methanogenesis, an outcome that
      is undesired. Here, we show that free ammonia-nitrogen (FAN, which is NH3)
      altered the glucose fermentation pathways in batch MECs, minimizing the
      production of H2, the "fuel" for hydrogenotrophic methanogens. Consequently, the
      Coulombic efficiency (CE) increased: 57% for 0.02 g of FAN/L of fed-MEC, compared
      to 76% for 0.18 g of FAN/L of fed-MECs and 62% for 0.37 g of FAN/L of fed-MECs.
      Increasing the FAN concentration was associated with the accumulation of higher
      organic acids (e.g., lactate, iso-butyrate, and propionate), which was
      accompanied by increasing relative abundances of phylotypes that are most closely
      related to anode respiration (Geobacteraceae), lactic-acid production
      (Lactobacillales), and syntrophic acetate oxidation (Clostridiaceae). Thus, the
      microbial community established syntrophic relationships among glucose
      fermenters, acetogens, and anode-respiring bacteria (ARB). The archaeal
      population of the MEC fed 0.02 g FAN/L was dominated by Methanobacterium, but
      0.18 and 0.37 g FAN/L led to Methanobrevibacter becoming the most abundant
      species. Our results provide insight into a way to decrease CH4 production and
      increase CE using FAN to control the fermentation step, instead of inhibiting
      methanogens using expensive or toxic chemical inhibitors, such as 2
      bromoethanesulfonic acid.

PMID- 29039193
TI  - Synthesis of Stable [28pi] m-Benzihexaphyrins (1.0.0.1.1.1).
AB  - Four new expanded [28pi] m-benziporphyrins (1.0.0.1.1.1) were synthesized by
      [3+3] condensation of 10,10'-bis[(p-toly)hydroxymethyl]-1,3-bis(2
      thienyl)benzenediol with various 16-tripyrranes such as 16-thiatripyrrane, 16
      oxatripyrrane, 16-azatripyrrane, and 16-selenatripyrrane under mild
      trifluoroacetic acid-catalyzed reaction conditions. The macrocycles are freely
      soluble in common organic solvents, and their identities were confirmed by HRMS
      and detailed 1D and 2D NMR spectroscopy. The macrocycles showed one sharp Soret
      type band at ~500 nm and broad ill-defined Q-type band(s) in the region 600-950
      nm, which supports their nonaromatic nature. Upon protonation, the macrocycles
      exhibited bathochromically shifted absorption bands with a distinct change in the
      color of the solutions. The preliminary studies carried out with one of the
      macrocycles indicated that the macrocycles have a weak tendency to form
      coordination complexes.

PMID- 29039194
TI  - Microbial Photoelectrosynthesis for Self-Sustaining Hydrogen Generation.
AB  - Current artificial photosynthesis (APS) systems are promising for the storage of
      solar energy via transportable and storable fuels, but the anodic half-reaction
      of water oxidation is an energy intensive process which in many cases poorly
      couples with the cathodic half-reaction. Here we demonstrate a self-sustaining
      microbial photoelectrosynthesis (MPES) system that pairs microbial
      electrochemical oxidation with photoelectrochemical water reduction for energy
      efficient H2 generation. MPES reduces the overall energy requirements thereby
      greatly expanding the range of semiconductors that can be utilized in APS. Due to
      the recovery of chemical energy from waste organics by the mild microbial process
      and utilization of cost-effective and stable catalyst/electrode materials, our
      MPES system produced a stable current of 0.4 mA/cm2 for 24 h without any external
      bias and ~10 mA/cm2 with a modest bias under one sun illumination. This system
      also showed other merits, such as creating benefits of wastewater treatment and
      facile preparation and scalability.

PMID- 29039195
TI  - Ru/Cu Photoredox or Cu/Ag Catalyzed C4-H Sulfonylation of 1-Naphthylamides at
      Room Temperature.
AB  - A mild and efficient protocol for C4-H sulfonylation of 1-naphthylamine
      derivatives with sodium sulfinates has been described. This C4 sulfonylation
      proceeded smoothly at room temperature under Ru/Cu photoredox catalysis or Cu/Ag
      cocatalysis and could tolerate various functional groups. In addition, control
      experiments suggested that this C4-H sulfonylation reaction might proceed via a
      single-electron-transfer process.

PMID- 29039196
TI  - A Mitochondria-Targeted Ratiometric Biosensor for pH Monitoring and Imaging in
      Living Cells with Congo-Red-Functionalized Dual-Emission Semiconducting Polymer
      Dots.
AB  - The accurate and sensitive monitoring and imaging of mitochondrial pH in living
      cells play vital roles in chemical biology and biomedicine. Herein, we design a
      novel ratiometric fluorescent chemical probe for monitoring and imaging the pH of
      mitochondria in living cells based on congo-red (CR)-modified dual-emission
      semiconducting polymer dots (Pdots) via a competitive fluorescence resonance
      energy transfer (FRET) mechanism. The Pdots are synthesized by
      triphenylphosphonium (TPP)-modified polyoxyethylene nonylphenylether (CO-520),
      poly(9,9-dioctylfluorenyl-2,7-diyl) (PFO), poly(9,9-dioctylfluorene)-co-(4,7-di-2
      thienyl-2,1,3-benzothiadiazole) (PF-DBT5), and poly(styrene-co-maleic anhydride)
      (PSMA) via a nanoprecipitation method, and the prepared Pdots are further
      chemically linked with pH-sensitive, nonfluorescent CR to obtain the mitochondria
      targeted pH fluorescent probes. This Pdots-based probe consists of two
      luminescent components including PFO and PF-DBT5 as fluorescence donors, an acid
      base indicator CR as an energy acceptor, and TPP as the mitochondria-targeting
      group. At a different pH region, the FRET efficiency between CR and PFO or CR and
      PF-DBT5 can be modulated. This probe exhibits good biocompatibility, a wide pH
      detection range from 2.57 to 8.96, good reversibility, high selectivity, and
      excellent photostability for pH monitoring. This probe allows for the detecting
      and imaging of mitochondrial pH in living cells with satisfactory results.

PMID- 29039197
TI  - Influence of the Grain Size on the Properties of CH3NH3PbI3 Thin Films.
AB  - Hybrid perovskites have already shown a huge success as an absorber in solar
      cells, resulting in the skyrocketing rise in the power conversion efficiency to
      more than eta = 22%. Recently, it has been established that the crystal quality
      is one of the most important parameters to obtain devices with high efficiencies.
      However, the influence of the crystal quality on the material properties is not
      fully understood. Here, the influence of the morphology on electronic properties
      of CH3NH3PbI3 thin films is investigated. Postannealing was used to vary the
      average grain size continuously from ~150 to ~1000 nm. Secondary grain growth is
      thermally activated with an activation energy of Ea = 0.16 eV. The increase in
      the grain size leads to an enhancement of the photoluminescence, indicating an
      improvement in the material quality. According to surface photovoltage
      measurements, the charge-carrier transport length exhibits a linear increase with
      increasing grain size. The charge-carrier diffusion length is limited by grain
      boundaries. Moreover, an improved morphology leads to a drastic increase in power
      conversion efficiency of the devices.

PMID- 29039198
TI  - Electrochemical Synthesis of Cu2O Concave Octahedrons with High-Index Facets and
      Enhanced Photoelectrochemical Activity.
AB  - High-index-faceted nano-/microcrystals exhibit enhanced catalytic activity and
      can thus serve as new-generation catalysts owing to their high density of low
      coordinated atoms, leading to significantly enhanced catalytic activity. In this
      study, an effective electrochemical approach termed cyclic scanning
      electrodeposition (CSE) was developed to convert a thin Cu film into Cu2O concave
      octahedrons enclosed by 24 {344} high-index facets at room temperature with high
      yield and high throughput. The formation mechanism and the role of each ion in
      the electrolyte were systematically studied, which facilitated the design of a
      high-index-faceted metal/metal oxide through CSE. We also presented a general
      formula to identify the structure of an individual crystal enclosed by {khh} high
      index facets based on the crystals oriented along three low-index zone axes and
      imaged by transmission electron microscopy. Experimental results demonstrated the
      Cu2O concave octahedrons to be highly efficient, cost-effective catalysts for
      photoelectrochemical hydrogen production. This new technology is a promising
      route for the synthesis of metal or metal oxide crystals with high activity and
      has a great potential for several advanced applications, such as clean energy
      conversion.

PMID- 29039199
TI  - Dielectric Breakdown in Chemical Vapor Deposited Hexagonal Boron Nitride.
AB  - Insulating films are essential in multiple electronic devices because they can
      provide essential functionalities, such as capacitance effects and electrical
      fields. Two-dimensional (2D) layered materials have superb electronic, physical,
      chemical, thermal, and optical properties, and they can be effectively used to
      provide additional performances, such as flexibility and transparency. 2D layered
      insulators are called to be essential in future electronic devices, but their
      reliability, degradation kinetics, and dielectric breakdown (BD) process are
      still not understood. In this work, the dielectric breakdown process of
      multilayer hexagonal boron nitride (h-BN) is analyzed on the nanoscale and on the
      device level, and the experimental results are studied via theoretical models. It
      is found that under electrical stress, local charge accumulation and charge
      trapping/detrapping are the onset mechanisms for dielectric BD formation. By
      means of conductive atomic force microscopy, the BD event was triggered at
      several locations on the surface of different dielectrics (SiO2, HfO2, Al2O3,
      multilayer h-BN, and monolayer h-BN); BD-induced hillocks rapidly appeared on the
      surface of all of them when the BD was reached, except in monolayer h-BN. The
      high thermal conductivity of h-BN combined with the one-atom-thick nature are
      genuine factors contributing to heat dissipation at the BD spot, which avoids
      self-accelerated and thermally driven catastrophic BD. These results point to
      monolayer h-BN as a sublime dielectric in terms of reliability, which may have
      important implications in future digital electronic devices.

PMID- 29039200
TI  - In Search of the Perfect Photocage: Structure-Reactivity Relationships in meso
      Methyl BODIPY Photoremovable Protecting Groups.
AB  - A detailed investigation of the photophysical parameters and photochemical
      reactivity of meso-methyl BODIPY photoremovable protecting groups was
      accomplished through systematic variation of the leaving group (LG) and core
      substituents as well as substitutions at boron. Efficiencies of the LG release
      were evaluated using both steady-state and transient absorption spectroscopies as
      well as computational analyses to identify the optimal structural features. We
      find that the quantum yields for photorelease with this photocage are highly
      sensitive to substituent effects. In particular, we find that the quantum yields
      of photorelease are improved with derivatives with higher intersystem crossing
      quantum yields, which can be promoted by core heavy atoms. Moreover, release
      quantum yields are dramatically improved by boron alkylation, whereas alkylation
      in the meso-methyl position has no effect. Better LGs are released considerably
      more efficiently than poorer LGs. We find that these substituent effects are
      additive, for example, a 2,6-diiodo-B-dimethyl BODIPY photocage features quantum
      yields of 28% for the mediocre LG acetate and a 95% quantum yield of release for
      chloride. The high chemical and quantum yields combined with the outstanding
      absorption properties of BODIPY dyes lead to photocages with uncaging cross
      sections over 10 000 M-1 cm-1, values that surpass cross sections of related
      photocages absorbing visible light. These new photocages, which absorb strongly
      near the second harmonic of an Nd:YAG laser (532 nm), hold promise for
      manipulating and interrogating biological and material systems with the high
      spatiotemporal control provided by pulsed laser irradiation, while avoiding the
      phototoxicity problems encountered with many UV-absorbing photocages. More
      generally, the insights gained from this structure-reactivity relationship may
      aid in the development of new highly efficient photoreactions.

PMID- 29039201
TI  - Optical Transmittance Enhancement of Flexible Copper Film Electrodes with a
      Wetting Layer for Organic Solar Cells.
AB  - The development of highly efficient flexible transparent electrodes (FTEs)
      supported on polymer substrates is of great importance to the realization of
      portable and bendable photovoltaic devices. Highly conductive, low-cost Cu has
      attracted attention as a promising alternative for replacing expensive indium tin
      oxide (ITO) and Ag. However, highly efficient, Cu-based FTEs are currently
      unavailable because of the absence of an efficient means of attaining an
      atomically thin, completely continuous Cu film that simultaneously exhibits
      enhanced optical transmittance and electrical conductivity. Here, strong two
      dimensional (2D) epitaxy of Cu on ZnO is reported by applying an atomically thin
      (around 1 nm) oxygen-doped Cu wetting layer. Analyses of transmission electron
      microscopy images and X-ray diffraction patterns, combined with first-principles
      density functional theory calculations, reveal that the reduction in the surface
      and interface free energies of the wetting layers with a trace amount (1-2 atom
      %) of oxygen are largely responsible for the two-dimensional epitaxial growth of
      the Cu on ZnO. The ultrathin 2D Cu layer, embedded between ZnO films, exhibits a
      highly desirable optical transmittance of over 85% in a wavelength range of 400
      800 nm and a sheet resistance of 11 Omega sq-1. The validity of this innovative
      approach is verified with a Cu-based FTE that contributes to the light-to
      electron conversion efficiency of a flexible organic solar cell that incorporates
      the transparent electrode (7.7%), which far surpasses that of a solar cell with
      conventional ITO (6.4%).

PMID- 29039202
TI  - Nanoelectronic Platform for Ultrasensitive Detection of Protein Biomarkers in
      Serum using DNA Amplification.
AB  - Silicon nanowire field effect transistors (NWFETs) are low noise, low power,
      ultrasensitive biosensors that are highly amenable to integration. However, using
      NWFETs to achieve direct protein detection in physiological buffers such as blood
      serum remains difficult due to Debye screening, nonspecific binding, and
      stringent functionalization requirements. In this work, we performed an indirect
      sandwich immunoassay in serum combined with exponential DNA amplification and pH
      measurement by ultrasensitive NWFET sensors. Measurements of model cytokine
      interleukin-2 concentrations from <20 fM to >200 pM were demonstrated, surpassing
      the conventional NWFET urease-based readout. Our approach paves way for future
      development of universal, highly sensitive, miniaturized, and integrated
      nanoelectronic devices that can be applied to a wide variety of analytes.

PMID- 29039203
TI  - Correction to "Nickel-Mediated Asymmetric Allylic Alkylation between Nitroallylic
      Acetates and Acyl Imidazoles".

PMID- 29039204
TI  - Access to Alkyl-Substituted Lactone via Photoredox-Catalyzed
      Alkylation/Lactonization of Unsaturated Carboxylic Acids.
AB  - An efficient photoredox-catalyzed alkylation/lactonization reaction of
      unsaturated carboxylic acids by using alkyl N-hydroxyphthalimide esters as
      alkylation reagents has been developed. Varieties of redox-active esters derived
      from aliphatic carboxylic acids were proved viable in this method, affording
      alkyl substituted lactones in moderate to good yields. This redox-neutral
      procedure features mild conditions and operational simplicity, which provides a
      new strategy for the synthesis of alkyl substituted lactones.

PMID- 29039205
TI  - Synthesis of Cardiopetaline via a Wagner-Meerwein Rearrangement without
      Preactivation of the Pivotal Hydroxy Group.
AB  - A synthesis of cardiopetaline has been accomplished via a Wagner-Meerwein
      rearrangement of a diol having the denudatine skeleton. The Wagner-Meerwein
      rearrangement could be facilitated simply by heating the diol with p
      toluenesulfonic acid in pivalic acid, without preactivating the pivotal hydroxy
      group. This strategy does not require differentiation of several hydroxy groups
      in the substrate for the Wagner-Meerwein rearrangement and could be applied to
      the synthesis of more highly oxygenated aconitine-type diterpenoid alkaloids.

PMID- 29039206
TI  - Oxidative stress in ischemia and reperfusion: current concepts, novel ideas and
      future perspectives.
AB  - Oxidative stress remains a major contributor to myocardial injury after ischemia
      followed by reperfusion (I/R) as the reperfusion of the myocardial infarction
      (MI) area inevitably leads to a cascade of I/R injury. This review focused on
      concepts of the antioxidative defense system and elucidates recent research using
      antioxidants like vitamin C, E and beta-carotene or essential trace elements to
      activate compounds of antioxidative pathways in the circulation. In this context,
      important defense mechanisms like superoxide dismutase and glutathione peroxidase
      will be described. Furthermore, the different mechanisms through which myocardial
      protection can be addressed, like ischemic postconditioning in myocardial
      infarction or adjunctive measures like targeted temperature management as well as
      new theories, including the role of iron in I/R injury, will be discussed.

PMID- 29039207
TI  - Stochastic Seasonal Models for Glucose Prediction in the Artificial Pancreas.
AB  - BACKGROUND: Linear empirical dynamic models have been widely used for glucose
      prediction. The extension of the concept of seasonality, characteristic of other
      domains, is explored here for the improvement of prediction accuracy. METHODS:
      Twenty time series of 8-hour postprandial periods (PP) for a same 60g
      carbohydrate meal were collected from a closed-loop controller validation study.
      A single concatenated time series was produced representing a collection of data
      from similar scenarios, resulting in seasonality. Variability in the resulting
      time series was representative of worst-case intrasubject variability. Following
      a leave-one-out cross-validation, seasonal and nonseasonal autoregressive
      integrated moving average models (SARIMA and ARIMA) were built to analyze the
      effect of seasonality in the model prediction accuracy. Further improvement
      achieved from the inclusion of insulin infusion rate as exogenous variable was
      also analyzed. Prediction horizons (PHs) from 30 to 300 min were considered.
      RESULTS: SARIMA outperformed ARIMA revealing a significant role of seasonality.
      For a 5-h PH, average MAPE was reduced in 26.62%. Considering individual runs,
      the improvement ranged from 6.3% to 54.52%. In the best-performing case this
      reduction amounted to 29.45%. The benefit of seasonality was consistent among
      different PHs, although lower PHs benefited more, with MAPE reduction over 50%
      for PHs of 60 and 120 minutes, and over 40% for 180 min. Consideration of insulin
      infusion rate into the seasonal model further improved performance, with a 61.89%
      reduction in MAPE for 30-min PH and reductions over 20% for PHs over 180 min.
      CONCLUSIONS: Seasonality improved model accuracy allowing for the extension of
      the PH significantly.

PMID- 29039208
TI  - First impressions of adults with autism improve with diagnostic disclosure and
      increased autism knowledge of peers.
AB  - A practical consideration for many intellectually able adults with autism
      spectrum disorder (ASD) is whether to disclose their diagnostic status or try to
      mask their autistic characteristics to avoid judgment and discrimination. Here,
      we assessed first impressions of adults with ASD and typically developing
      controls ( N = 40) made by typically developing observers ( N = 215) when their
      diagnostic status was either withheld, accurately provided, or inaccurately
      provided. First impressions were less favorable for ASD participants compared to
      typically developing controls across a range of judgments, but were significantly
      more positive when accurately labeled as ASD compared to when no label was
      provided, when mislabeled as typically developing, or when mislabeled as having
      schizophrenia. For typically developing participants, ratings did not change when
      accurately labeled but improved when mislabeled as ASD. Greater autistic traits
      for the ASD and typically developing participants were associated with less
      favorable first impressions, and females were rated more favorably than males.
      Autism knowledge of the raters, but not age, IQ, or autistic traits, was
      positively associated with more favorable impressions of ASD participants.
      Collectively, these findings suggest that first impressions for intellectually
      able adults with ASD improve with diagnostic disclosure and increased autism
      understanding on the part of peers.

PMID- 29039209
TI  - Re: Brent L. Finley, Stacey M. Benson & Gary M. Marsh (2017): Cosmetic talc as a
      risk factor for pleural mesothelioma: a weight of evidence evaluation of the
      epidemiology, Inhalation Toxicology, DOI: 10.1080/08958378.2017.1336187.

PMID- 29039210
TI  - Mailbox Tox: Ingestion of a Pharmaceutical Product Stolen From a Mailbox.

PMID- 29039211
TI  - Synergistic effects of heat and antibiotics on Pseudomonas aeruginosa biofilms.
AB  - Upon formation of a biofilm, bacteria undergo several changes that prevent
      eradication with antimicrobials alone. Due to this resistance, the standard of
      care for infected medical implants is explantation of the infected implant and
      surrounding tissue, followed by eventual reimplantation of a replacement device.
      Recent studies have demonstrated the efficacy of heat shock for biofilm
      eradication. To minimize the heat required for in situ biofilm eradication, this
      study investigated the hypothesis that antibiotics, while ineffective by
      themselves, may substantially increase heat shock efficacy. The combined effect
      of heat and antibiotics on Pseudomonas aeruginosa biofilms was quantified via
      heat shock in combination with ciprofloxacin, tobramycin, or erythromycin at
      multiple concentrations. Combined treatments had synergistic effects for all
      antibiotics for heat shock conditions of 60 degrees C for 5 min to 70 degrees C
      for 1 min, indicating an alternative to surgical explantation.

PMID- 29039212
TI  - Propagation and titration of infectious bursal disease virus, including non-cell
      culture-adapted strains, using ex vivo-stimulated chicken bursal cells.
AB  - Infectious bursal disease virus (IBDV) is a Birnaviridae family member of
      economic importance for poultry. This virus infects and destroys developing B
      lymphocytes in the cloacal bursa, resulting in a potentially fatal or
      immunosuppressive disease in chickens. Naturally occurring viruses and many
      vaccine strains are not able to grow in in vitro systems without prior
      adaptation, which often affects viral properties such as virulence. Primary
      bursal cells, which are the main target cells of lymphotropic IBDV in vivo, may
      represent an attractive system for the study of IBDV. Unfortunately, bursal cells
      isolated from bursal follicles undergo apoptosis within hours following their
      isolation. Here, we demonstrate that ex vivo stimulation of bursal cells with
      phorbol 12-myristate 13-acetate maintains their viability long enough to allow
      IBDV replication to high titres. A wide range of field-derived or vaccine
      serotype 1 IBDV strains could be titrated in these phorbol 12-myristate 13
      acetate -stimulated bursal cells and furthermore were permissive for replication
      of non-cell-culture-adapted viruses. These cells also supported multistep
      replication experiments and flow cytometry analysis of infection. Ex vivo
      stimulated bursal cells therefore offer a promising tool in the study of IBDV.

PMID- 29039213
TI  - Do patients take angioplasty seriously?

PMID- 29039214
TI  - Pharmaceutical pricing in Japan: market evidence for rheumatoid arthritis
      treatment.
AB  - BACKGROUND: Drug price setting is one of the key challenges faced by the Japanese
      health care system. This study aims to identify the determinants of drug price in
      Japan using the example of the rheumatoid arthritis (RA) treatment market.
      RESEARCH DESIGN AND METHODS: In order to compare prices across different
      products, we calculated prices per defined daily dose using WHO methodology.
      Price determinants were calculated both at launch and over time using IMS
      quarterly data on medicines approved for RA treatment in Japan from 2012 to 2015.
      Pharmaceutical pricing was modeled as a function of clinical and economic
      variables using regression analysis. RESULTS: For prices at the launch we found
      that differences in efficacy are not reflected in price differentials. We also
      report that the number of products within a molecule class had a negative effect
      on prices while originator drugs maintained higher prices. CONCLUSION: Although
      the existing pricing rules in Japan are very comprehensive they do not
      necessarily capture differences in product characteristics. The findings here
      support the notion that competitive forces are weak in highly regulated markets
      such as Japan.

PMID- 29039215
TI  - A clinical assessment and lung tissue burden from an individual who worked as a
      Libby vermiculite miner.
AB  - During its days of operation (1920s-1990), the world's largest source of
      vermiculite was extracted from a mine located near Libby, Montana. The material
      mined at this site was shipped for various commercial applications to numerous
      sites in the United States. There was a "fibrous" component with toxic potential
      within the vermiculite deposit that has resulted in "asbestos-like"
      diseases/deaths being reported in numerous studies involving miners as well as
      residents of the town of Libby. The present case involves the clinical
      assessments of an individual who worked at the mine from 1969 to 1990. He had no
      other known occupational exposures to fibrous materials. He developed a clinical
      picture that included "asbestos-like" pathological features and eventually an
      adenocarcinoma. The clinical assessment including radiographic features will be
      presented. The evaluation will also include the analytical evaluation of the
      fibrous/ferruginous body composition of the lung tissue. This is to our knowledge
      the first time such an extensive evaluation has been conducted in a vermiculite
      miner from Libby, Montana.

PMID- 29039216
TI  - Breast cancer screening and migrants: exploring targeted messages for Moroccan
      migrant women in Brussels.
AB  - OBJECTIVES: This study explored views of Moroccan migrant women on barriers and
      facilitators to the organized breast cancer screening program in Brussels
      (Belgium), and the potential of targeted printed invitations to increase this
      population's attendance to the program. METHODS: We conducted one expert
      interview with the breast cancer screening program coordinator on current
      practices and challenges with regards to inviting Moroccan migrant women in
      Brussels for screening. Secondly, we held focus groups with Moroccan women aged
      26-66. Sessions focused on perspectives on breast cancer screening and the
      existing generic program invitations. Directed content analysis of transcripts
      was based on the Health Belief Model. Alternative communication packages were
      developed based on barriers and suggestions from the focus groups. A second round
      of focus groups looked at the alternative communication packages and their
      potential to encourage Moroccan migrant women in Brussels to participate in the
      organized breast cancer screening program. RESULTS: Alternative packages were
      appreciated by some, but a number of adjustments did not catch participants'
      attention. Printed communication delivered by post does not appear to be the
      preferred means of communication to encourage breast cancer screening for
      Moroccan migrant women in Brussels, nor does it seem appropriate to address the
      barriers to screening found in this study. CONCLUSIONS: The benefit of targeted
      postal invitation packages for Moroccan migrant women in Brussels seems limited
      for a variety of reasons. For future research, a large-scale study analyzing the
      topic in a cross-cultural perspective is warranted.

PMID- 29039218
TI  - The integration of genomics testing and functional proteomics in the era of
      personalized medicine.

PMID- 29039217
TI  - The role of metabolomics in tuberculosis treatment research.
AB  - Despite the fact that tuberculosis (TB) is a curable disease, it still results in
      approximately 1.8 million deaths annually. Various inadequacies in the current TB
      treatment strategies are major contributors to this high disease prevalence,
      including the long duration of therapy, the severe side effects associated with
      TB drugs, treatment failure due to drug resistance, post-treatment disease
      relapse, and HIV co-infection. In this review, we describe how metabolomics has
      contributed toward better explaining/elucidating the mechanisms of drug
      action/metabolism, drug toxicity and microbial drug resistance, and how
      metabolite biomarkers may serve as prognostic indicators for predicting treatment
      outcome as well as for the development of new TB drugs. We also discuss possible
      future contributions that metabolomics can make toward more efficient, less toxic
      TB treatment strategies.

PMID- 29039219
TI  - Allergic Contact Cheilitis From a Variety of Lip Balm Ingredients.

PMID- 29039221
TI  - How useful is urinary-free cortisol in the clinic?
AB  - Measurement of 24-h urine-free cortisol is frequently employed as a first-line
      screening and disease-monitoring test in Cushing's syndrome (CS). The quest for
      'cortisol specificity' has seen the emergence of mass spectrometry (MS) based
      assays, particularly liquid chromatography/tandem mass spectrometry. In contrast
      to traditional immunoassays, liquid chromatography/tandem mass spectrometry 'free
      cortisol' measurement is less susceptible to 'interference' from cortisol
      precursors and metabolites. However, detection of these conjugates is important
      in mild CS and therefore, missed by MS if cortisol alone is measured. MS assays
      nevertheless are capable of measuring broad steroid profiles, including the
      potential to distinguish benign from malignant adrenal-based CS and detection of
      exogenous glucocorticoids. Until this is routine practice, we recommend against
      abandoning immunoassays measurement of urine-free cortisol.

PMID- 29039220
TI  - Function of glutaredoxin 3 (Grx3) in oxidative stress response caused by iron
      homeostasis disorder in Candida albicans.
AB  - AIM: Glutaredoxin is a conserved oxidoreductase in eukaryotes and prokaryotes.
      This study aimed to determine the role of Grx3 in cell survival, iron homeostasis
      and the oxidative stress response in Candida albicans. MATERIALS & METHODS: A
      grx3Delta/Delta mutant was obtained using PCR-mediated homologs recombination.
      The function of Grx3 was investigated by a series of biochemical methods.
      RESULTS: Deletion of GRX3 impaired growth and cell cycle, disturbance of iron
      homeostasis and activated the oxidative stress response. Furthermore, disruption
      of GRX3 caused oxidative damage and growth defects of C. albicans. CONCLUSION:
      Our findings provide new insights into the role of GRX3 in C. albicans.

PMID- 29039222
TI  - Association between haptoglobin gene and insulin resistance in Arab-Americans.
AB  - AIM: To analyze associations between variation in the HP gene and lipid and
      glucose-related measures in Arab-Americans. Secondary analyses were performed
      based on sex. PATIENTS & METHODS: Genomic DNA was extracted from samples obtained
      from a previous epidemiological study of diabetes in Arab-Americans. The HP 1 and
      2 alleles were analyzed by polymerase chain reaction and gel electrophoresis.
      Associations were analyzed by linear regression. RESULTS & CONCLUSION:
      Associations were identified between the heterozygous haptoglobin 2-1 genotype
      and insulin resistance, fasting insulin and fasting c-peptide. The effect of sex
      did not remain significant after adjustment for relevant variables. HP genetic
      variation may have utility as a biomarker of insulin resistance and diabetes risk
      in Arab-Americans, however, future prospective studies are needed.

PMID- 29039223
TI  - Predictors of excessive use of social media and excessive online gaming in Czech
      teenagers.
AB  - Background and aims Young people's involvement in online gaming and the use of
      social media are increasing rapidly, resulting in a high number of excessive
      Internet users in recent years. The objective of this paper is to analyze the
      situation of excessive Internet use among adolescents in the Czech Republic and
      to reveal determinants of excessive use of social media and excessive online
      gaming. Methods Data from secondary school students (N = 4,887) were collected
      within the 2015 European School Survey Project on Alcohol and Other Drugs.
      Logistic regression models were constructed to describe the individual and
      familial discriminative factors and the impact of the health risk behavior of (a)
      excessive users of social media and (b) excessive players of online games.
      Results The models confirmed important gender-specific distinctions - while girls
      are more prone to online communication and social media use, online gaming is far
      more prevalent among boys. The analysis did not indicate an influence of family
      composition on both the excessive use of social media and on excessive online
      gaming, and only marginal effects for the type of school attended. We found a
      connection between the excessive use of social media and binge drinking and an
      inverse relation between excessive online gaming and daily smoking. Discussion
      and conclusion The non-existence of significant associations between family
      environment and excessive Internet use confirmed the general, widespread of this
      phenomenon across the social and economic strata of the teenage population,
      indicating a need for further studies on the topic.

PMID- 29039224
TI  - Comparison of brain connectivity between Internet gambling disorder and Internet
      gaming disorder: A preliminary study.
AB  - Background and aims Given the similarities in clinical symptoms, Internet gaming
      disorder (IGD) is thought to be diagnostically similar to Internet-based gambling
      disorder (ibGD). However, cognitive enhancement and educational use of Internet
      gaming suggest that the two disorders derive from different neurobiological
      mechanisms. The goal of this study was to compare subjects with ibGD to those
      with IGD. Methods Fifteen patients with IGD, 14 patients with ibGD, and 15
      healthy control subjects were included in this study. Resting-state functional
      magnetic resonance imaging data for all participants were acquired using a 3.0
      Tesla MRI scanner (Philips, Eindhoven, The Netherlands). Seed-based analyses, the
      three brain networks of default mode, cognitive control, and reward circuitry,
      were performed. Results Both IGD and ibGD groups demonstrated decreased
      functional connectivity (FC) within the default-mode network (DMN) (family-wise
      error p < .001) compared with healthy control subjects. However, the IGD group
      demonstrated increased FC within the cognitive network compared with both the
      ibGD (p < .01) and healthy control groups (p < .01). In contrast, the ibGD group
      demonstrated increased FC within the reward circuitry compared with both IGD (p <
      .01) and healthy control subjects (p < .01). Discussion and conclusions The IGD
      and ibGD groups shared the characteristic of decreased FC in the DMN. However,
      the IGD group demonstrated increased FC within the cognitive network compared
      with both ibGD and healthy comparison groups.

PMID- 29039226
TI  - Reconstruction of Traumatic Dorsal Loss of the Thumb: Four Different Surgical
      Approaches.
AB  - BACKGROUND: This article outlines our methods for thumb reconstruction following
      dorsal skin loss injury located between the metacarpophalangeal joint (MPj) and
      the entire nail affecting skin, nail, tendon, and bone in different combinations
      but with intact sensate palmar skin. METHODS: Between 1990 and 2015, 24 patients
      were treated for dorsal thumb defects using 4 different surgical techniques. Five
      cases of dorsal compound traumatic loss were reconstructed by custom-made dorsal
      great toe transfer. Four patients with dorsal skin and nail loss located at the
      distal phalanx level were covered with the homodigital flap with reverse flow
      vascularization. In 9 patients presenting skin defects between the MPj and the
      nail, reconstruction was achieved by means of the kite flap. Six cases suffered
      extensive dorsal skin loss, and reconstruction was performed using different
      types of radial forearm flaps (cutaneous, tendineocutaneous, osteocutaneous, and
      fascial). RESULTS: Flap survival was obtained in all cases. No vascular
      complications occurred with free vascularized compound toe transfer. CONCLUSIONS:
      Reconstruction of dorsal thumb defects is imperative and its approach is strictly
      correlated to type of defect, patient's requests, and flap alternatives. For
      defects with nail involvement, the free osteo-onychocutaneous flap harvested from
      the great toe provides the best aesthetic result in selected young and well
      motivated patients. An alternative is represented by the dorsoulnar flap, when
      the defect is located distally, or the fascial pedicle radial forearm flap, for
      major dorsal thumb defects, in patients refusing microsurgical reconstruction.
      The kite flap still represents a feasible solution for medium-size defects with
      an intact nail.

PMID- 29039227
TI  - The Violent Accounts of Men Diagnosed With Comorbid Antisocial and Borderline
      Personality Disorders.
AB  - This study explored the violent offence accounts of life-sentenced prisoners
      diagnosed with comorbid antisocial personality disorder (ASPD) and borderline
      personality disorder (BPD). The aim of the current study was to gain needed
      clinical insight into the mechanisms involved in this specific group offenders'
      use of violence against others. Six adult male personality-disordered offenders
      were interviewed via a semistructured interview schedule to collate individual
      offence accounts. Interview transcripts were analyzed by the lead researcher
      (first author) using interpretative phenomenological analysis (IPA) who compared
      and contrasted findings to develop superordinate themes across the group.
      External auditing analysis was conducted by the second researcher. Four
      superordinate themes resulted. These were "A victim of a hostile and rejecting
      world," "Self as unacceptable to others," "Unwanted emotions that cannot be
      tolerated or controlled," and "Violent revenge as catharsis." The results support
      the view that emotional dysregulation is central in driving acts of violence in
      those with comorbid ASPD/BPD; nevertheless, shame was particularly prevalent.
      Thus an argument is made for the adaptation of evidence-based treatments for this
      specific forensic population to ensure a particular focus on helping men tolerate
      feelings of shame. The limitations of the study are also discussed.

PMID- 29039225
TI  - Toxicological impact of waterpipe smoking and flavorings in the oral cavity and
      respiratory system.
AB  - Waterpipe smoking (WS), an emerging trend has major health concerns. It is
      prevalent worldwide as a recreational activity both indoors and outdoors. The aim
      of this review was to assess the impact of waterpipe smoke on the oral and
      respiratory system (oral cavity and pulmonary tissues). A number of studies have
      shown that periodontal health status is compromised in waterpipe smokers when
      compared with nonsmokers. Some studies have associated WS with oral premalignant
      and malignant lesions; however, due to the poor quality of these studies, the
      presented outcomes should be interpreted with caution. Although cigarette smoking
      has been considered as a potential risk factor for dental caries; there are no
      studies in indexed literature that have shown an association to exist between
      dental caries and WS. Inhaled waterpipe smoke imposes oxidative stress and
      inflammatory responses and compromises the ventilatory capacity of the lungs and
      may lead to an increased risk of decline in lung function. WS may cause oral and
      pulmonary diseases, such as periodontal disease and chronic obstructive airway
      disease, respectively. The association between WS and development of dental
      caries and oral pre-cancer and their relationships with chronic airways disease
      requires investigations. This review discusses the current evidence of waterpipe
      smoke effects on the oral health and respiratory system based on basic and
      clinical science and provides future directions for research and regulatory
      science on how WS can affect the oral cavity and the respiratory/pulmonary
      system.

PMID- 29039228
TI  - Evaluation of the respiratory tract toxicity of ortho-phthalaldehyde, a proposed
      alternative for the chemical disinfectant glutaraldehyde.
AB  - ortho-Phthalaldehyde (OPA) is a high-level chemical disinfectant that is commonly
      used for chemical sterilization of dental and medical instruments as an
      alternative to glutaraldehyde, a known skin and respiratory sensitizer. Concern
      for safe levels of human exposure remains due to a lack of toxicity data as well
      as human case reports of skin and respiratory sensitization following OPA
      exposure. The present study evaluated the inhalational toxicity of OPA in Harlan
      Sprague-Dawley rats and B6C3F1/N mice. Groups of 10 male and female rats and mice
      were exposed to OPA by whole-body inhalation for 3 months at concentrations of 0
      (control), 0.44, 0.88, 1.75, 3.5, or 7.0 ppm. Rats and mice developed a spectrum
      of lesions at sites of contact throughout the respiratory tract (nose, larynx,
      trachea, lung), as well as in the skin and eye, consistent with a severe irritant
      response. In general, histologic lesions (necrosis, inflammation, regeneration,
      hyperplasia and metaplasia) occurred at deeper sites within the respiratory tract
      with increasing exposure concentration. As a first site of contact, the nose
      exhibited the greatest response to OPA exposure and resulted in an increased
      incidence, severity and variety of lesions compared to a previous study of
      glutaraldehyde exposure at similar exposure concentrations. This increased
      response in the nasal cavity, combined with extensive lesions throughout the
      respiratory tract, provides concern for use of OPA as a replacement for
      glutaraldehyde as a high-level disinfectant.

PMID- 29039229
TI  - Exposure to allethrin-based mosquito coil smoke during gestation and postnatal
      development affects reproductive function in male offspring of rat.
AB  - The threat of zika virus looms throughout the world and the use of allethrin
      based mosquito coils to prevent mosquito bites during and postpregnancy is on the
      rise. The aim of this study was to analyze the toxic effects of exposure to
      allethrin-based mosquito coil smoke in rats under conditions that reflect human
      settings. Pregnant female rats were exposed to mosquito coil smoke and same was
      continued to the male pups up to 111 days postparturition (21-day weaning plus up
      to 90 days postweaning). Increased oxidative stress, distorted antioxidant enzyme
      status, downregulation of genes involved in spermatogenesis, sperm maturation and
      steroidogenesis was observed. Daily sperm production, total sperm count and
      acrosome reaction was compromised. Results of our study indicate the toxic
      effects of exposure to allethrin-based mosquito coil smoke in male offspring and
      calls for preventing mosquito coil use during pregnancy and postnatal
      development. Community-based programs that will encourage general population to
      use classical methods such as use of mosquito nets, keeping the surroundings
      clean and use of natural mosquito repellents should be conducted.

PMID- 29039230
TI  - Effect of prenatal waterpipe tobacco smoke on airway inflammation in murine model
      of asthma of adult offspring mice.
AB  - OBJECTIVE: Worldwide popularity of waterpipe tobacco smoking has increased,
      including in pregnant women. This study investigates the effect of prenatal
      waterpipe tobacco smoke (WTS) exposure on airway inflammation in a murine model
      of asthma of adult offspring mice. MATERIALS AND METHODS: Pregnant BALB/c mice
      were exposed to fresh air or WTS, using a whole-body exposure system that mimics
      human use during WTS. Adult male offspring mice were divided into; (1) control
      (prenatal fresh air, postnatal ovalbumin sensitization and saline challenge), (2)
      postnatal Ova S/C (prenatal fresh air, postnatal ovalbumin sensitization and
      challenge (Ova S/C)), (3) prenatal WTS (prenatal WTS, postnatal ovalbumin
      sensitization and saline challenge) and (4) prenatal WTS + postnatal Ova S/C.
      Cells from the bronchoalveolar lavage fluid, cytokines, and oxidative stress
      markers (superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and
      thiobarbituric acid reactive substances (TBARS)) from lung homogenates were
      evaluated. RESULTS: Prenatal WTS increased recruitment of cells in lungs and
      levels of SOD and catalase when compared to unexposed offspring's. The levels of
      cytokines, GPx and TBARS were not affected by prenatal WTS. Prenatal WTS exposure
      and postnatal Ova S/C increased airway inflammation and activity of SOD compared
      to control and Ova S/C mice and reduced IL-18 levels compared to Ova S/C mice.
      DISCUSSION AND CONCLUSIONS: Prenatal exposure to WTS induced airway inflammation,
      further enhanced by a murine model of asthma in adult offspring. Prenatal
      exposure to WTS adversely affects the lung function of the offspring and careful
      strategies for increasing public awareness regarding the harmful effects of WTS
      during pregnancy is important.

PMID- 29039231
TI  - The respiratory health effects of geogenic (earth derived) PM10.
AB  - Inhalation of particulate matter less than 10 um in diameter (PM10) has a range
      of implications for respiratory health. In order to mitigate these effects
      regulatory bodies have set ambient air quality guidelines based on the known dose
      response relationships between PM10 exposure and health outcomes. However, these
      data are based almost entirely on PM10 from urban regions, which are typically
      dominated by particulates from combustion sources. In contrast, there are limited
      data on the respiratory health effects of particles from nonurban regions that
      often contain a high geogenic (earth derived) component. In this narrative
      review, we summarize the existing evidence for the respiratory health effects of
      inhalation of geogenic PM10. We outline the impact of physicochemical properties
      on the lung response, with a view to identifying gaps in the field.

PMID- 29039232
TI  - Letter on: "Cosmetic talc as a risk factor for pleural mesothelioma: a weight of
      evidence evaluation of the epidemiology".

PMID- 29039233
TI  - The relationships of classic psychedelic use with criminal behavior in the United
      States adult population.
AB  - Criminal behavior exacts a large toll on society and is resistant to
      intervention. Some evidence suggests classic psychedelics may inhibit criminal
      behavior, but the extent of these effects has not been comprehensively explored.
      In this study, we tested the relationships of classic psychedelic use and
      psilocybin use per se with criminal behavior among over 480,000 United States
      adult respondents pooled from the last 13 available years of the National Survey
      on Drug Use and Health (2002 through 2014) while controlling for numerous
      covariates. Lifetime classic psychedelic use was associated with a reduced odds
      of past year larceny/theft (aOR = 0.73 (0.65-0.83)), past year assault (aOR =
      0.88 (0.80-0.97)), past year arrest for a property crime (aOR = 0.78 (0.65
      0.95)), and past year arrest for a violent crime (aOR = 0.82 (0.70-0.97)). In
      contrast, lifetime illicit use of other drugs was, by and large, associated with
      an increased odds of these outcomes. Lifetime classic psychedelic use, like
      lifetime illicit use of almost all other substances, was associated with an
      increased odds of past year drug distribution. Results were consistent with a
      protective effect of psilocybin for antisocial criminal behavior. These findings
      contribute to a compelling rationale for the initiation of clinical research with
      classic psychedelics, including psilocybin, in forensic settings.

PMID- 29039234
TI  - Risk of Development of Second Primary Head and Neck Cancer following an Index
      Breast Cancer.
AB  - Objective Many head and neck cancers (HNCs) have genomic features seen in breast
      malignancy. We sought to analyze the risk of second primary HNC following an
      index breast cancer. Study Design Retrospective cohort study. Setting National
      database from the SEER registry (Surveillance, Epidemiology, and End Results).
      Subjects and Methods Within the SEER database, 223,423 women diagnosed with index
      breast cancer from 1992 to 2002 were identified. We calculated standard incidence
      ratios (SIRs) for all head and neck sites with 10-year follow-up. Results Women
      diagnosed with an index breast cancer did not exhibit higher likelihood of
      developing second primary HNC (SIR = 0.99; 95% CI, 0.90-1.07). The risk was
      determined for each subsite of the head and neck, and salivary gland cancer
      presented the highest risk. Patients with index breast cancer were 83% more
      likely to develop salivary gland cancer than what would be expected in the
      general population (SIR = 1.83; 95% CI, 1.49-2.22). An overall trend of increased
      risk was observed for salivary gland cancers between 1992 and 2002. There was no
      significant higher risk observed for the other head and neck subsites. Conclusion
      Patients with index breast cancer did not have a higher-than-expected risk of
      developing HNC. We did find an increased incidence of salivary gland cancers
      among patients with index breast cancer. Patients were 80% more likely to develop
      salivary gland cancer than that expected within the population. These findings
      warrant further investigation on the relationship between salivary gland and
      breast malignancy.

PMID- 29039235
TI  - Short-term Subjective and Objective Outcomes of Patients Receiving Endoscopic
      Transcanal Myringoplasty for Repairing Tympanic Perforations.
AB  - Objective Endoscopic transcanal myringoplasty (ETM) has been an emerging
      technique for repairing tympanic perforations since the late 1990s. Objective
      outcomes (ie, graft success rates and hearing results) of patients who received
      ETM are well documented; however, subjective outcomes of these patients have
      rarely been reported. Hence, this study evaluated subjective and objective
      outcomes of patients who received ETM for repairing tympanic perforations. Study
      Design Prospective study. Setting Tertiary care university hospital. Patients and
      Methods Patients who underwent ETM for perforations of the tympanic membrane were
      included. We evaluated subjective variables of patients receiving ETM as the
      primary outcome and objective variables as the secondary outcome. Results In
      total, 91 ears that underwent ETM were included. The mean pain scale score was
      0.1 (range, 0-2) on postoperative day 3. The mean duration of pain medication was
      2.0 (range, 0-3) days. The mean number of days required to resume routine
      activities was 1.0 (range, 1-2) days. The overall graft success was determined
      postoperatively at 3 months in 80 of 91 ears (87.9%). Closure of the air-bone gap
      to within 20 dB was achieved in 79 (86.8%) ears. Conclusion In this study,
      patients who received ETM had mild postoperative pain and resumed routine
      activities early. These patients also exhibited favorable graft success rates and
      hearing results at 3 months postoperatively. On the basis of our results, we
      conclude that patients who receive ETM for the repair of tympanic perforations
      have favorable short-term subjective and objective outcomes.

PMID- 29039236
TI  - Social inequalities in self-rated health: A comparative cross-national study
      among 32,560 Nordic adolescents.
AB  - AIMS: We aimed to estimate the magnitude of socioeconomic inequality in self
      rated health among Nordic adolescents (aged 11, 13 and 15 years) using the Family
      Affluence Scale (a composite measure of material assets) and perceived family
      wealth as indicators of socioeconomic status. METHODS: Data were collected from
      the Health Behaviour in School-aged Children (HBSC) survey in 2013-2014. A sample
      of 32,560 adolescents from Denmark, Norway, Finland, Iceland, Greenland and
      Sweden was included in the study. Age-adjusted regression analyses were used to
      estimate associations between fair or poor self-rated health and the ridit scores
      for family affluence and perceived wealth. RESULTS: The pooled relative index of
      inequality of 2.10 indicates that the risk of fair or poor health was about twice
      as high for young people with the lowest family affluence relative to those with
      the highest family affluence. The relative index of inequality for observed
      family affluence was highest in Denmark and lowest in Norway. For perceived
      family wealth, the pooled relative index of inequality of 3.99 indicates that the
      risk of fair or poor health was about four times as high for young people with
      the lowest perceived family wealth relative to those with the highest perceived
      family wealth. The relative index of inequality for perceived family wealth was
      highest in Iceland and lowest in Greenland. CONCLUSIONS: Social inequality in
      self-rated health among adolescents was found to be robust across subjective and
      objective indicators of family affluence in the Nordic welfare states.

PMID- 29039237
TI  - SGLT2 inhibitors: are they safe?
AB  - Sodium-glucose linked transporter type 2 (SGLT2) inhibitors are a relatively new
      class of antidiabetic drugs with positive cardiovascular and kidney effects. The
      aim of this review is to present the safety issues associated with SGLT2
      inhibitors. Urogenital infections are the most frequently encountered adverse
      events, although tend to be mild to moderate and are easily manageable with
      standard treatment. Although no increased acute kidney injury risk was evident in
      the major trials, the mechanism of action of these drugs requires caution when
      they are administered in patients with extracellular volume depletion or with
      drugs affecting renal hemodynamics. Canagliflozin raised the risk of amputations
      and the rate of fractures in the CANVAS trial, although more data are necessary
      before drawing definite conclusions. The risk of euglycemic diabetic ketoacidosis
      seems to be minimal when the drugs are prescribed properly. Regarding other
      adverse events, SGLT2 inhibitors do not increase the risk of hypoglycemia even
      when co-administered with insulin, but a decrease in the dose of sulphonylureas
      may be needed. The available data do not point to a causative role of SGLT2
      inhibitors on malignancy risk, however, these drugs should be used with caution
      in patients with known hematuria or history of bladder cancer. SGLT2 inhibitors
      seem to be safe and effective in the treatment of diabetes but more studies are
      required to assess their long-term safety.

PMID- 29039238
TI  - Sensory Reduction on the General Milieu of a High-Acuity Inpatient Psychiatric
      Unit to Prevent Use of Physical Restraints: A Successful Open Quality Improvement
      Trial.
AB  - BACKGROUND: Impaired sensory gating in patients with acute mental illness
      predisposes to overstimulation and behavioral dyscontrol. OBJECTIVE: Explore use
      of sensory reduction interventions on a high-acuity inpatient milieu to reduce
      high assault/restraint rates. DESIGN: A multidisciplinary team using failure mode
      and effect analysis to explore high restraint use between 4:00 p.m. and 7:00 p.m.
      observed patient/staff overstimulation contributed to behavioral escalations. The
      team implemented sensory reduction/integration improvements over a 5-month period
      to prevent excessive restraint use. RESULTS: Restraint rates dropped immediately
      following light and sound reduction interventions and by 72% at 11 months
      postimplementation. Mann-Whitney statistics for unpaired 6-month comparisons, 1
      year pre- and postintervention showed significant reductions: Assault rates
      (median pre = 1.37, post = 0.18, U = 4, p = .02); Restraint rates (median pre =
      0.50, post = 0.06, U = 0, p = .002). CONCLUSION: Sensory reduction during a high
      stress time period on a high-acuity psychiatric unit was associated with a
      reduction in assaults and restraints.

PMID- 29039239
TI  - How Do People Experience Early Intervention Services for Psychosis? A Meta
      Synthesis.
AB  - We conducted a study to explore how people diagnosed with first-episode psychosis
      experienced their contact with early intervention services for psychosis and the
      way these experiences relate to their recovery processes. Our aim was to
      integrate and describe the service users' experiences in a rigorous and
      comprehensive way. A broad literature search was performed in June and July 2016.
      After screening, 17 qualitative studies were included. We analyzed the findings
      in two main steps: (a) translating studies into one another and (b) synthesizing
      the findings from the studies. Through these interpretative processes, we found
      five new and overarching themes: (a) something is wrong, (b) do for myself, (c)
      it's about people, (d) a price to pay, and (e) ongoing vulnerability. We describe
      these themes as a process that service users' maneuver through in their contact
      with the services. Our findings are discussed in light of relevant research.

PMID- 29039240
TI  - Repeated study of items with and without repeated context: aging effects on
      memory discriminability.
AB  - Presenting items multiple times during encoding is a common way to enhance
      recognition accuracy. Under such conditions, older adults often show an increase
      in false recognition that counteracts benefits of repeated study. Using a false
      memory paradigm with related study items and related lures, we tested whether
      repetition within the same encoding task or repetition across two different
      encoding tasks would be more beneficial to older adults' memory discriminability.
      Results showed that, compared to items not repeated at study, items repeated in
      the same context and items repeated across different contexts showed improvements
      in memory discriminability in both young and older adults. This improvement was
      primarily reflected in improved recollection responses for both age groups across
      both repeat study conditions, as compared to no repetition. Importantly, the
      results demonstrated that repetition can be used to successfully mitigate age
      related deficits by increasing memory discriminability and without incurring a
      cost of false recognition specific to any one age group.

PMID- 29039241
TI  - Aripiprazole long-acting injection - a mirror image study of its effects on
      hospitalisation at one year.
AB  - Second generation antipsychotic long-acting injections have a greater cost than
      older depots. Their cost-effectiveness has yet to be established. We conducted a
      non-interventional, observational, follow-up of patients prescribed aripiprazole
      long-acting injection in two centres using a mirror image method. Data were
      available for 160 patients consecutively prescribed aripiprazole long-acting
      injection, of whom 30 were not included in the analysis (21 forensic patients,
      five incomplete data and four lost to follow-up). Of the 130 patients, 66 (51%)
      remained on aripiprazole long-acting injection at one year. The mean number of
      bed days in the year following aripiprazole long-acting injection initiation
      reduced to 22.82/patient (standard deviation [SD]=55.07) from 30.09/patient/year
      (SD=30.40) over the three years before initiation ( p<0.001). The mean number of
      admissions fell from 0.71/patient/year (SD=0.55) to 0.45/patient/year (SD=0.93)
      over the same period ( p<0.001). The median number of bed days in the three years
      before aripiprazole long-acting injection was 21.67/year; in the year following
      it was zero. Outcomes were not statistically better in those who remained on
      aripiprazole long-acting injection at one year compared with those who
      discontinued. The prescribing of aripiprazole long-acting injection reduces
      average bed days and admissions compared with prior treatments. The reduction in
      bed days is of a magnitude that renders aripiprazole long-acting injection
      broadly cost-neutral.

PMID- 29039242
TI  - Computational elucidation, mutational and hot spot-based designing of potential
      inhibitors against human acid-sensing ion channels (hASIC-1a) to treat various
      physiological conditions.
AB  - Acid-sensing ion channels are ligand/proton-gated ion channels belonging to the
      family of the degenerin/epithelial Na+ channel (DEG/ENaC). They function as a
      sodium-selective pore for Ca2+ entry into neuronal cells during pathological
      conditions. The blocking of this channel has therapeutic importance, because at
      basal physiological pH (7.2), it is in a closed state and under a more acidic
      condition, and the ASIC1a ion channel is activated. To investigate the different
      states of the hASIC1a channel based on mutational analysis, structure-based
      virtual screening and molecular dynamics simulation studies. The system showed
      stability after 30 ns (after 1500 frame), and it was stabilized to an average
      value around 2.2A. During the simulation, the ion channel residues in persistent
      contact with toxin PcTx1 were D237, E238, D347, D351, E219 and E355. These
      residues are important physiologically for the activation of the channel. From in
      silico alanine scanning, the significant hotspots obtained in hASIC1 are E344,
      P347, F352, D351, E355 and E219. From the sitemap analysis, it was evident that
      the sitemap found one of the active sites at the PcTx1 binding site with a site
      score of 1.086 and a D-score of 1.035 for hASIC1. We obtained a few promising
      hits and final potential hits from the virtual screening in hASIC1 that made
      interactions with the residues in the acidic pocket (E344, P347, F352, D351, E355
      and E219). Based on these studies, the hits and scaffolds of potential
      therapeutic interest against various pathological conditions are associated with
      hASIC1a for future studies.

PMID- 29039245
TI  - Jumping into the world of social media with Palliative Medicine.

PMID- 29039243
TI  - A Novel Approach to Oropharyngeal Foreign Body Removal.
AB  - Grill wire brush bristle foreign bodies most commonly embed in the oropharynx.
      Often these bristles can be removed in the clinic; however, on occasion, the
      patient requires general anesthesia for retrieval because of the gag reflex and
      difficulty with access and visualization. We report here on 2 cases of patients
      who underwent successful transoral robotic surgical retrieval of wire bristles
      from the base of tongue after unsuccessful direct laryngoscopy. Otolaryngologists
      should be aware of the use of robotic assistance for oropharyngeal foreign body
      retrieval.

PMID- 29039246
TI  - Regular Practice of Competitive Sports Does Not Impair Sleep in Adolescents:
      DADOS Study.
AB  - PURPOSE: To analyze differences in sleep quality and duration by athletic status
      and sex, and to examine the association between physical activity (PA)
      recommendation and sleep in adolescents. METHODS: A total of 267 adolescents
      [13.9 (0.3) y] from Deporte, ADOlescencia y Salud (DADOS) study (129 girls) were
      included in this cross-sectional analysis. Athletes competed regularly in
      organized sport events and trained >=3 days per week, but nonathletes did not
      compete. PA was assessed by GENEActiv accelerometer. PA values were dichotomized
      into inactive (<60 min/d of moderate and vigorous PA) and active (>=60 min/d of
      moderate and vigorous PA). Sleep quality was evaluated with the Spanish version
      of the Pittsburgh Sleep Quality Index. Pittsburgh Sleep Quality Index values were
      dichotomized into >5 (poor quality) or <=5 (good quality). Sleep duration was
      objectively measured by accelerometer. RESULTS: Sleep quality and duration were
      not statistically different between athletes [median (Mdn) = 4.0, interquartile
      range (IQR) = 3.0-6.0 and Mdn = 8.0, IQR = 7.4-8.6 h, respectively] and
      nonathletes (Mdn = 5.0, IQR = 3.0-7.0 and Mdn = 7.9; IQR = 7.3-8.6 h,
      respectively), P > .05. Nonathlete or inactive adolescents did not show higher
      risk for poor sleep quality or short sleep duration than athletes [odds ratio
      (OR) = 1.17; 95% confidence interval (CI), 0.68-2.00 and OR = 0.93; 95% CI, 0.56
      1.55, respectively] or active peers (OR = 1.39; 95% CI, 0.66-2.89 and OR = 1.62;
      95% CI, 0.78-3.37, respectively). CONCLUSIONS: In our group of adolescents,
      competitive sport practice did not alter sleep patterns. PA recommendations for
      adolescents may not discriminate between good and poor sleepers.

PMID- 29039247
TI  - High throughput in silico identification and characterization of Plasmodium
      falciparum PRL phosphatase inhibitors.
AB  - Kinases and phosphatases are involved in many essential processes in Plasmodium
      lifecycle. Among the identified 67 Plasmodium falciparum phosphatases,
      Phosphatase of Regenerating Liver (PRL) family protein homolog, PfPRL, is an
      essential parasite tyrosine phosphatase. PfPRL is shown to be prenylated,
      secreted, and involved in the host invasion process. In the present study, a
      structure-based high throughput in silico screening of PfPRL binders, using
      ChEMBL-NTD compounds lead to the identification of nine compounds based on
      binding energy, Lipinski rule of five, and QED score. The most of the shortlisted
      compounds are known to inhibit parasite growth at a concentration (EC50) <=2 MUm
      in in vitro P. falciparum culture assays. MD simulations were carried out on the
      shortlisted nine potential enzyme-inhibitor complexes to analyze specificity,
      stability, and to calculate the free binding energies of the complexes. The study
      identifies PfPRL as one of the potential drug targets for selected ChEMBL-NTD
      compounds that may be exploited as a scaffold to develop novel antimalarials.

PMID- 29039248
TI  - Impact of Resident Participation on Operative Time and Outcomes in Otologic
      Surgery.
AB  - Objectives To describe the impact of resident involvement in tympanoplasty on
      operative time and surgical complication rates. Study Design Case series with
      chart review. Setting Tertiary medical center. Subjects and Methods Current
      Procedural Terminology codes were used to identify patients in the 2011-2014
      public use files of the American College of Surgeons National Surgical Quality
      Improvement Program who underwent a tympanoplasty or tympanomastoidectomy. Cases
      were included if the database indicated whether the operating room was staffed
      with an attending alone or an attending with residents. Categorical and
      continuous variables were compared with chi-square, Fisher's exact, and Mann
      Whitney U tests. Generalized linear models with a log-link and gamma distribution
      were used to examine the factors affecting operative time. Results Overall, 1045
      cases met our study criteria (tympanoplasty, n = 797; tympanomastoidectomy, n =
      248). Resident involvement increased mean operative time for tympanoplasties by
      46% (107 vs 73 minutes, P < .001) and tympanomastoidectomies by 49% (175 vs 117
      minutes, P < .001). While controlling for confounding factors, the variable with
      the largest impact on operative time was resident involvement. There were no
      significant differences observed in the rate of surgical complications between
      attending-alone and attending-resident cases. Conclusion Resident involvement in
      tympanoplasty and tympanomastoidectomy did not affect the surgical complication
      rate. Resident involvement increased operative time for tympanoplasties and
      tympanomastoidectomies; however, the specific reasons for the increase are not
      explained by the available data.

PMID- 29039249
TI  - Visualizing a Vibrio cholerae O1 El Tor typing bacteriophage belonging to the
      Myoviridae group and the packaging of its genomic ends inside the phage capsid.
AB  - Phage D10, an O1 El Tor tying vibriophage, has been successfully employed to
      tract the outspread of cholera epidemic. Using Transmission Electron Microscopy
      and computational image analysis, we have determined the structures of the
      capsid, head-to-tail connector, the contractile helical tail, the baseplate and
      combined them to form the complete three-dimensional (3D) D10 phage structure.
      Using partial denaturation experiments on the genome and using the computed 3D
      structure of the phage, we have established the packing of the genome ends inside
      the capsid together with the release styles during the phage infection,
      respectively. Finally, using the 3D density maps of the different components of
      the D10 phage, we have presented a simplified picture of morphogenesis of the D10
      vibriophage. Using the complete assembled structure of the D10 phage, we have
      traced the path of the phage genome during the infection process, all the way
      from the phage head down the tail tube of the tail to the top of the baseplate.
      To the best of our knowledge, this is first structural study for a long-tailed
      vibriophage. We have tabulated the structural features of the different
      components of the phages belonging to the Myoviridae and Siphoviridae. The
      comparative study suggested the possibility of a common origin of the
      bacteriophages, irrespective of belonging to different groups and species.

PMID- 29039250
TI  - Predictors of Clinicopathologic Stage Discrepancy in Oropharyngeal Squamous Cell
      Carcinoma: A National Cancer Database Study.
AB  - Objective To determine the frequency, associated factors, and prognosis of
      clinicopathologic stage discrepancy in oropharyngeal squamous cell carcinoma
      (OPSCC). Study Design Retrospective study using a national database. Setting
      National Cancer Database. Subjects and Methods Cases of OPSCC diagnosed between
      January 1, 2004, and December 31, 2013, with full clinical and pathologic staging
      information available were identified. Demographic, clinicopathologic, and
      treatment variables associated with overall stage discrepancy were identified by
      multivariate logistic regression analysis. Results In total, 7731 cases of OPSCC
      were identified. Overall stage discrepancy was present in 30.2% of cases (21.9%
      upstaging, 8.2% downstaging). A total of 13.1% of cases were T-upstaged, and
      10.5% of cases were T-downstaged; 22.9% of cases were N-upstaged, and 8.6% of
      cases were N-downstaged. Upstaging by overall stage was associated with a high
      Charlson-Deyo score, high tumor grade, number of lymph nodes examined, and
      increasing tumor size. No factors were positively associated with downstaging.
      High tumor grade was negatively associated with downstaging. For stage II, III,
      and IVA tumors, upstaging was associated with poorer OS. Conclusion
      Clinicopathologic stage discrepancy is common in OPSCC and is likely attributable
      to insensitive clinical staging techniques as well as to intrinsic tumor biologic
      properties. Upstaging is associated with poorer prognosis, which is likely due to
      advancement of disease.

PMID- 29039251
TI  - Eye-Tracking Causality.
AB  - How do people make causal judgments? What role, if any, does counterfactual
      simulation play? Counterfactual theories of causal judgments predict that people
      compare what actually happened with what would have happened if the candidate
      cause had been absent. Process theories predict that people focus only on what
      actually happened, to assess the mechanism linking candidate cause and outcome.
      We tracked participants' eye movements while they judged whether one billiard
      ball caused another one to go through a gate or prevented it from going through.
      Both participants' looking patterns and their judgments demonstrated that
      counterfactual simulation played a critical role. Participants simulated where
      the target ball would have gone if the candidate cause had been removed from the
      scene. The more certain participants were that the outcome would have been
      different, the stronger the causal judgments. These results provide the first
      direct evidence for spontaneous counterfactual simulation in an important domain
      of high-level cognition.

PMID- 29039252
TI  - Western-style diet induces object recognition deficits and alters complexity of
      dendritic arborization in the hippocampus and entorhinal cortex of male rats.
AB  - OBJECTIVE: Research demonstrates a link between diet-induced obesity and
      cognitive impairments; however, no studies have utilized the Sholl analysis to
      assess changes in dendritic arborization as a possible cause of obesity-induced
      memory deficits. Therefore, the purpose of this study was to examine the effect
      of a Western-style diet (WSD) on memory and dendritic complexity of male Sprague
      Dawley rats. METHODS: Male Sprague-Dawley rats (n = 18) were fed either a control
      or WSD. Spatial memory and episodic memory were assessed using the Morris Water
      Maze and novel object recognition (NOR) tasks, respectively. At termination,
      brains were removed and prepared with the Golgi-Cox method. Stained neurons in
      both the hippocampus and entorhinal cortex (EC) were imaged and digitally
      reconstructed. RESULTS: Results indicated significant differences in percent body
      fat and TNFalpha levels between dietary conditions. WSD males also experienced
      reduced NOR exploration ratios, but no deficits in spatial memory were observed.
      Analysis of dendritic length and number of branch points revealed no significant
      differences in either the EC or the hippocampus; however, the Sholl analysis
      indicated that a WSD increased neuronal complexity in the EC. DISCUSSION: Sholl
      analysis of the EC suggests a possible diet-induced dysfunction of pruning, which
      may contribute to reduced performance on the NOR task. Elevated TNFalpha levels
      indicate a putative role of inflammation in neuronal remodeling. The results
      demonstrate the importance of investigating mechanisms underlying obesity-related
      cognitive impairments.

PMID- 29039253
TI  - Stakeholder-Driven Quality Improvement: A Compelling Force for Clinical Practice
      Guidelines.
AB  - Clinical practice guideline development should be driven by rigorous methodology,
      but what is less clear is where quality improvement enters the process: should it
      be a priority-guiding force, or should it enter only after recommendations are
      formulated? We argue for a stakeholder-driven approach to guideline development,
      with an overriding goal of quality improvement based on stakeholder perceptions
      of needs, uncertainties, and knowledge gaps. In contrast, the widely used topic
      driven approach, which often makes recommendations based only on randomized
      controlled trials, is driven by epidemiologic purity and evidence rigor, with
      quality improvement a downstream consideration. The advantages of a stakeholder
      driven versus a topic-driven approach are highlighted by comparisons of
      guidelines for otitis media with effusion, thyroid nodules, sepsis, and acute
      bacterial rhinosinusitis. These comparisons show that stakeholder-driven
      guidelines are more likely to address the quality improvement needs and pressing
      concerns of clinicians and patients, including understudied populations and
      patients with multiple chronic conditions. Conversely, a topic-driven approach
      often addresses "typical" patients, based on research that may not reflect the
      needs of high-risk groups excluded from studies because of ethical issues or a
      desire for purity of research design.

PMID- 29039255
TI  - Gaps Between Self-Rated Job Importance and Abilities for Community Health Workers
      in Massachusetts.
AB  - Introduction Community health workers (CHWs) serve increasingly active roles in
      clinical care and population health. To identify priorities for training
      programs, we developed a training needs assessment (TNA) tool by integrating and
      distilling core competencies previously identified by various national and state
      agencies. Methods CHWs were asked to self-rate, using a 4-point scale, the
      importance to their work and their ability to perform 49 competencies categorized
      under 10 domains. A difference score-Ability minus Importance-was calculated to
      determine relative Need. Results The 96 CHWs who completed the TNA were mostly
      female (80%) and Latino (40%). While CHWs indicated training was needed for all
      competencies, the scores ranged from -0.04 to -0.45, on a scale running from 0 to
      -3, where larger negative numbers indicate higher need. In general, there was a
      high level of congruence between individual competencies with high Need and
      domains with Need, with few outliers. Competencies with high Need scores related
      to culture, case assessment and coordination, and behavior change. CHWs rated
      client-based competencies higher than population health competencies in Ability
      scores (3.43 vs. 3.05, respectively) and Importance scores (3.70 vs. 3.35,
      respectively). However, overall Need scores showed no difference between client
      based and public health-based competencies. Conclusion CHWs can successfully rate
      the importance of core competencies to their work and rank their ability to
      perform these competencies. Training needs generally favored clinical individual
      client-focused skills over prevention and public health competencies. Using
      scales that incorporate self-rated measures of core competency ability and
      importance can inform priorities for CHW training programs and contribute to
      successful curriculum development.

PMID- 29039256
TI  - Ethical Considerations in Microbial Therapeutic Clinical Trials.
AB  - As understanding of the human microbiome improves, novel therapeutic targets to
      improve human health with microbial therapeutics will continue to expand. We
      outline key considerations of balancing risks and benefits, optimising access,
      returning key results to research participants, and potential conflicts of
      interest.

PMID- 29039257
TI  - First Description of Male and Larval Female of Parasitic Mite Eutarsopolipus
      abdominis (Acari: Podapolipidae) with Redescription of the Adult Female.
AB  - Male and larval female of the parasitic mite Eutarsopolipus abdominis Regenfuss,
      1968 (Acari: Prostigmata: Podapolipidae) belonging to the myzus species group are
      described and illustrated for the first time on the basis of the materials
      recovered from under elytra of Agonum sp. (Coleoptera: Carabidae) from Mazandaran
      Province, northern Iran. A redescription of the adult female is also provided. It
      is the first record of this species from Asia and fourth representative of
      parasitic mites of the myzus species group found from Iran. Furthermore, this
      finding revealed the first record of the association between tribe Platynini
      (Coleoptera: Carabidae: Harpalinae) and mites of myzus species group, and one of
      the highest levels of polyxeny among mites of the genus Eutarsopolipus.

PMID- 29039254
TI  - The antidepressant efficacy of subanesthetic-dose ketamine does not correlate
      with baseline subcortical volumes in a replication sample with major depressive
      disorder.
AB  - BACKGROUND: This study sought to reproduce, in a larger sample, previous findings
      of a correlation between smaller raw 3-Tesla (3T) hippocampal volumes and
      improved antidepressant efficacy of ketamine in individuals with major depressive
      disorder (MDD). A secondary analysis stratified subjects according to functional
      BDNF rs6265 (val66met) genotype. METHODS: Unmedicated subjects with treatment
      resistant MDD ( n=55) underwent baseline structural 3T MRI. Data processing was
      conducted with FSL/FIRST and Freesurfer software. The amygdala, hippocampus, and
      thalamus were selected a priori for analysis. All subjects received a single
      0.5mg/kg * 40-minute ketamine infusion. Pearson correlations were performed with
      subcortical volumes and percent change in MADRS score (from baseline to 230
      minutes, 1 day, and 1 week post-infusion). RESULTS: Raw and corrected subcortical
      volumes did not correlate with antidepressant response at any timepoint. In
      val/val subjects ( n=23), corrected left and right thalamic volume positively
      correlated with antidepressant response to ketamine at 230 minutes post-infusion
      but did not reach statistical significance. In met carriers ( n=14), corrected
      left and right thalamic volume negatively correlated with antidepressant response
      to ketamine. CONCLUSION: Baseline subcortical volumes implicated in MDD did not
      correlate with ketamine's antidepressant efficacy. Baseline thalamic volume and
      BDNF genotype may be a combinatorial rapid antidepressant response biomarker.

PMID- 29039258
TI  - Diagnosis and Treatment of Laryngeal Schwannoma: A Systematic Review.
AB  - Objective This review summarizes the clinical features, diagnostic workup, and
      surgical treatment of laryngeal schwannoma with the aim of providing guidance for
      the management of this rare disease. The collated data allowed the statistical
      testing of several hypotheses, including the efficacy of endoscopic vs open
      surgical intervention and the usefulness of preoperative biopsy. Data Sources
      PubMed, Google Scholar, Cochrane, and SCOPUS. Review Methods Basic
      epidemiological and clinical presentation data were collated together with
      details of diagnostic image modality, lesion attributes, and the use of
      preoperative biopsy. Surgical approach to intervention and outcome was also
      collated and simple statistical analyses applied. Results The 60 original
      articles selected provided a combined cohort of 74 patients for review. The
      combined data revealed that schwannoma with pedunculated morphology were always
      safely removed by endoscopic resection regardless of size and should be treated
      as a separate entity. Of the nonpedunculated schwannoma, larger tumors were more
      likely to undergo an open approach, which in turn was associated with higher
      rates of tracheotomy and postoperative vocal fold paralysis. The small cohort did
      not reveal a significant association between surgery type and persistent disease.
      Interestingly, the data revealed a significant association between the use of
      incisional biopsy and persistent disease. Cases exhibiting extralaryngeal
      extension of the lesion were shown to exclusively belong to patients with
      neurofibromatosis/schwannomatosis syndromes. Conclusions Taken together, these
      findings suggest that incisional biopsy should be avoided, and given the benign
      nature of the pathology, the least invasive radical approach should be employed.

PMID- 29039259
TI  - Single-camera visual odometry to track a surgical X-ray C-arm base.
AB  - This study provides a framework for a single-camera odometry system for
      localizing a surgical C-arm base. An application-specific monocular visual
      odometry system (a downward-looking consumer-grade camera rigidly attached to the
      C-arm base) is proposed in this research. The cumulative dead-reckoning
      estimation of the base is extracted based on frame-to-frame homography
      estimation. Optical-flow results are utilized to feed the odometry. Online
      positional and orientation parameters are then reported. Positional accuracy of
      better than 2% (of the total traveled distance) for most of the cases and 4% for
      all the cases studied and angular accuracy of better than 2% (of absolute
      cumulative changes in orientation) were achieved with this method. This study
      provides a robust and accurate tracking framework that not only can be integrated
      with the current C-arm joint-tracking system (i.e. TC-arm) but also is capable of
      being employed for similar applications in other fields (e.g. robotics).

PMID- 29039260
TI  - Medicinal cannabis (Bedrolite) substitution therapy in inpatients with a
      psychotic disorder and a comorbid cannabis use disorder: A case series.
AB  - Cannabis use disorders are frequently comorbid in patients with a psychotic
      disorder and are associated with worse outcomes. To date there are no proven
      effective strategies to achieve cannabis abstinence in this population. An
      alternative for abstinence might be harm reduction, i.e. replacing the use of
      street cannabis with high tetrahydrocannabinol and low cannabidiol levels by
      medicinal cannabis variants with relatively low tetrahydrocannabinol and
      relatively high cannabidiol levels, thereby reducing the psychosis inducing
      effects of cannabis and enhancing the antipsychotic effects of cannabis. Here we
      present the data of a case series with seven inpatients diagnosed with a
      psychotic disorder and a treatment-resistant cannabis use disorder who received
      substitution therapy with a low tetrahydrocannabinol medicinal cannabis variant
      (Bedrolite). The results suggest that the low tetrahydrocannabinol medicinal
      cannabis variant Bedrolite is not effective in the treatment of inpatients with a
      psychotic disorder and comorbid cannabis use disorder. Bedrolite is thus not very
      likely to become an effective harm reduction strategy in these patients.

PMID- 29039261
TI  - One-Year Follow-up of the CAPO Kids Trial: Are Physical Benefits Maintained?
AB  - PURPOSE: To determine the 12-month maintenance of a 9-month, thrice-weekly, 10
      minute high-intensity exercise program, delivered in schools, on bone and other
      health-related performance variables in prepubertal children. METHODS: All
      participants (N = 311) of the CAPO kids trial (testing times T1-T2) were
      contacted to undergo retesting (T3) of all original measures-including weight,
      standing and sitting height, calcaneal broadband ultrasound attenuation
      (Achilles, GE), and stiffness index (Achilles, GE)-waist circumference, resting
      heart rate, blood pressure, vertical jump, and aerobic capacity. Maturity was
      determined by estimating age of peak height velocity using sex-specific
      regression equations. RESULTS: A total of 240 children [12.3 (0.6) y old] were
      included in the current study (77% of initial follow-up sample at T2). Between
      the T2 and T3 time points, both exercise (EX) group and control (CON) group
      increased broadband ultrasound attenuation (EX: 5.6%, P <= .001; CON: 6.5%, P <=
      .001), stiffness index (EX: 7.3%, P <= .001; CON: 5.2%, P <= .001), vertical jump
      (EX: 5.9%, P <= .001; CON: 6.3%, P <= .001), estimated maximal oxygen consumption
      (EX: 13.3%, P <= .001; CON: 12.1%, P <= .001), and reduced waist circumference
      (EX: -5.2%, P <= .001; CON: -5.6%, P <= .001), with no between-group differences
      in the magnitude of those changes. No differences were detected in absolute
      values between groups at T3. CONCLUSION: Although the statistically significant
      differences observed between groups following the intervention were no longer
      significant 1 year after withdrawal of the intervention, the between-group
      similarities in growth trajectories of those parameters could suggest that some
      benefit of the intervention for bone health, waist circumference, and physical
      performance endured.

PMID- 29039262
TI  - Translating the Canadian Occupational Performance Measure to Danish, addressing
      face and content validity.
AB  - BACKGROUND: The Canadian Occupational Performance Measure (COPM) is a recognized
      assessment tool within Danish occupational therapy (OT), and translated versions
      of the COPM have been implemented in Danish OT practice. However, a rigorous
      translation and cross-cultural validation process has not been applied to these
      versions. AIMS: To produce a new Danish translation of the COPM evaluating its
      semantic, conceptual, operational and item equivalence while addressing its face
      and content validity. METHODS: An iterative, multistage translation process was
      undertaken with (1) forward translation involving professional translators and
      bilingual OTs, (2) pilot testing and cognitive debriefing interviews with 15 OTs
      and 37 clients which were analyzed quantitatively and qualitatively, and (3)
      finalization with adaptations, back translation and approval. RESULTS: Content
      validity of COPM in terms of appropriateness, acceptability, intelligibility and
      comprehensiveness was found in 78-100% of the cases, and its ability to ensure a
      client-centred focus in the assessment process was confirmed. However, issues
      concerning the administration and content of the COPM were identified.
      Subsequently, two recommendations regarding the administration of the COPM were
      added to the Danish version. CONCLUSION: Semantic, conceptual, operational and
      aspects of item equivalence of the COPM into Danish were achieved and supported
      by face and content validity.

PMID- 29039263
TI  - Integrating family planning services into HIV care: use of a point-of-care
      electronic medical record system in Lilongwe, Malawi.
AB  - BACKGROUND: Integrating family planning (FP) services into human immunodeficiency
      virus (HIV) clinical care helps improve access to contraceptives for women living
      with HIV. However, high patient volumes may limit providers' ability to counsel
      women about pregnancy risks and contraceptive options. OBJECTIVES: To assess
      trends in the use of contraceptive methods after implementing an  electronic
      medical record (EMR) system with FP questions and determine the reasons for non
      use of contraceptives among women of reproductive age (15-49 years) receiving
      antiretroviral therapy (ART) at the Martin Preuss Center clinic in Malawi.
      METHODS: In February 2012, two FP questions were incorporated into the ART EMR
      system (initial FP EMR module) to prompt providers to offer contraceptives to
      women. In July 2013, additional questions were added to the FP EMR module
      (enhanced FP EMR) to prompt providers to assess risks of unintended pregnancies,
      solicit reasons for non-use of contraceptives and offer contraceptives to non
      pregnant women . We conducted a retrospective, longitudinal cohort study using
      the EMR routinely collected data. The primary outcome was the use of any modern
      contraceptive method. Descriptive statistics were used to describe the study
      population and report trends in contraceptive use during the initial and enhanced
      study periods. RESULTS: Between February 2012 and December 2016, in HIV clinics,
      20,253 women of reproductive age received ART, resulting in 163,325 clinic visits
      observations. The proportion of women using contraceptives increased
      significantly from 18% to 39% between February 2012 and June 2013, and from 39%
      to 67% between July 2013 and December 2016 (chi-square for trend p < 0.001).
      Common reasons reported for the non-use of contraceptives among those at risk of
      unintended pregnancy were: pregnancy ambivalence (n = 234, 51%) and never thought
      about it (n = 133, 29%). CONCLUSION: Incorporating the FP EMR module into HIV
      clinical care prompted healthcare workers to encourage the use of contraceptives.

PMID- 29039264
TI  - "Football is a boys' game": children's perceptions about barriers for physical
      activity during recess time.
AB  - The aim of the study was to know the factors that influence boys and girls'
      perceptions for performing physical activity during playground recess from their
      own perspective. Ninety-eight schoolchildren aged 8-11 years from five schools
      from Cuenca (Spain) participated in 22 focus groups and carried out 98 drawings
      following the socioecological model as a theoretical framework. A content
      analysis of the transcripts from the focus groups and drawings was carried out by
      three researchers. Results showed that, in spite of boys and girls identified
      same barriers, there were gender differences in their perceptions. Gender
      socialization was the key as central category and helped to understand these
      differences. Boys preferred play football and this sport had a monopoly on the
      recess space. Weather was a barrier for boys. Girls and boys, who did not play
      football, were relegated to peripheral areas and lack of materials was a barrier
      for them. Teachers were a barrier for all children who did not play football.
      Thus, in order to promote recess physical activity, researchers, teachers and
      educational policy makers should take into account gender socialization and
      promote inclusive non-curricular physical activity in schools.

PMID- 29039266
TI  - Hand surgery in the Czech Republic.

PMID- 29039267
TI  - Letter and reply.

PMID- 29039265
TI  - HIV prevention trial design in an era of effective pre-exposure prophylaxis.
AB  - Pre-exposure prophylaxis (PrEP) has demonstrated remarkable effectiveness
      protecting at-risk individuals from HIV-1 infection. Despite this record of
      effectiveness, concerns persist about the diminished protective effect observed
      in women compared with men and the influence of adherence and risk behaviors on
      effectiveness in targeted subpopulations. Furthermore, the high prophylactic
      efficacy of the first PrEP agent, tenofovir disoproxil fumarate/emtricitabine
      (TDF/FTC), presents challenges for demonstrating the efficacy of new candidates.
      Trials of new agents would typically require use of non-inferiority (NI) designs
      in which acceptable efficacy for an experimental agent is determined using pre
      defined margins based on the efficacy of the proven active comparator (i.e.
      TDF/FTC) in placebo-controlled trials. Setting NI margins is a critical step in
      designing registrational studies. Under- or over-estimation of the margin can
      call into question the utility of the study in the registration package. The
      dependence on previous placebo-controlled trials introduces the same issues as
      external/historical controls. These issues will need to be addressed using trial
      design features such as re-estimated NI margins, enrichment strategies, run-in
      periods, crossover between study arms, and adaptive re-estimation of sample
      sizes. These measures and other innovations can help to ensure that new PrEP
      agents are made available to the public using stringent standards of evidence.

PMID- 29039269
TI  - Educational mission and international reach of the Journal.

PMID- 29039268
TI  - Correct reporting and interpretation of clinical data.

PMID- 29039270
TI  - Commentary on: The effect of adding active flexion to modified Kleinert regime on
      outcomes for zone 1 to 3 flexor tendon repairs. A prospective randomized trial.

PMID- 29039271
TI  - Social multiplier effects: academics' and practitioners' perspective on the
      benefits of a tuberculosis operational research capacity-building program in
      Indonesia.
AB  - BACKGROUND: The Tuberculosis Operational Research Group (TORG) implemented a
      capacity-building model involving academics and practitioners (i.e. clinicians or
      program staff) in an operational research (OR) team in Indonesia. OBJECTIVE: This
      study explored academics' and practitioners' perspectives regarding the benefits
      of participating in a tuberculosis (TB) OR capacity-building program in
      Indonesia. METHODS: We conducted a qualitative study involving in-depth
      interviews with 36 academics and 23 practitioners undertaking the TORG capacity
      building program. We asked open-ended questions about their experience of the
      program. Data were analyzed via content analysis. RESULTS: The findings
      demonstrated the social multiplier effects of the OR capacity-building program.
      Both academics and practitioners reported perceived improvements in research
      knowledge, skills, and experience, and described additional individual- and
      institutional-level benefits. The individual-level benefits level included
      improvements in understanding of the TB program, motivation for research and self
      satisfaction, the development/enhancement of individual networking, receipt of
      recognition, and new opportunities. The additional benefits reported at an
      institutional level included improvement in research curricula, in-house
      training, and program management and the development/enhancement of institutional
      partnerships. CONCLUSIONS: The program improved not only individuals' capacity
      for conducting OR but also the quality of the TB program management and public
      health education. OR should be included in research methodology curricula for
      postgraduate public health/disease control programs. The capacity-building model,
      in which academics and program staff collaborated within an OR team, should be
      promoted.

PMID- 29039272
TI  - Editorial: Precursors of Cardiovascular Disease in Adolescent Type 1 Diabetes.

PMID- 29039273
TI  - In vitro selection of Phytomonas serpens cells resistant to the calpain inhibitor
      MDL28170: alterations in fitness and expression of the major peptidases and
      efflux pumps.
AB  - The species Phytomonas serpens is known to express some molecules displaying
      similarity to those described in trypanosomatids pathogenic to humans, such as
      peptidases from Trypanosoma cruzi (cruzipain) and Leishmania spp. (gp63). In this
      work, a population of P. serpens resistant to the calpain inhibitor MDL28170 at
      70 u m (MDLR population) was selected by culturing promastigotes in increasing
      concentrations of the drug. The only relevant ultrastructural difference between
      wild-type (WT) and MDLR promastigotes was the presence of microvesicles within
      the flagellar pocket of the latter. MDLR population also showed an increased
      reactivity to anti-cruzipain antibody as well as a higher papain-like proteolytic
      activity, while the expression of calpain-like molecules cross-reactive to anti
      Dm-calpain (from Drosophila melanogaster) antibody and calcium-dependent cysteine
      peptidase activity were decreased. Gp63-like molecules also presented a
      diminished expression in MDLR population, which is probably correlated to the
      reduction in the parasite adhesion to the salivary glands of the insect vector
      Oncopeltus fasciatus. A lower accumulation of Rhodamine 123 was detected in MDLR
      cells when compared with the WT population, a phenotype that was reversed when
      MDLR cells were treated with cyclosporin A and verapamil. Collectively, our
      results may help in the understanding of the roles of calpain inhibitors in
      trypanosomatids.

PMID- 29039274
TI  - Different Escherichia coli B2-ST131 clades (B and C) producing extended-spectrum
      beta-lactamases (ESBL) colonizing residents of Portuguese nursing homes.
AB  - ESBL-producing Enterobacteriaceae and particularly Escherichia coli ST131
      isolates producing CTX-M enzymes are commonly found colonizing the intestine of
      nursing home (NH) residents, but ST131 subclonal structure has been scarcely
      explored in this vulnerable population. Our goal was to perform a pilot study to
      assess the faecal carriage rate and epidemiological features of ESBL- and/or
      carbapenemase-producing Enterobacteriaceae (ESBL-E and CPE, respectively) among
      NH residents. For this purpose, faecal samples from residents at 4 different NHs
      in the North of Portugal (representing 9.5% of the residents' population, July
      2014) were screened for ESBL-E and/or CPE by phenotypic and genotypic methods.
      Clonal structure and plasmid typing of ESBL-producing E. coli (ESBL-Ec) was
      performed by PCR and sequencing. Four ESBL-Ec isolates (2 CTX-M-15/2 CTX-M-14)
      were found in 20% of the samples, all belonging to the pandemic clonal lineage B2
      ST131-O25b:H4. Two different clades were identified, the C2/H30-Rx-virotype C
      producing CTX-M-15 and an atypical B/H22-like-virotype D5 (producing CTX-M-14 and
      fluoroquinolone-resistant), firstly described in Portugal. This pilot study
      highlights the role of NH residents as a source of different ST131 clades,
      besides emphasizing the importance of E. coli B2-ST131 subtyping in different
      clinical settings, and understanding the transmission dynamics of the different
      variants.

PMID- 29039275
TI  - Visuospatial Functioning in the Primary Progressive Aphasias.
AB  - OBJECTIVES: The aim of this study was to identify whether the three main primary
      progressive aphasia (PPA) variants would show differential profiles on measures
      of visuospatial cognition. We hypothesized that the logopenic variant would have
      the most difficulty across tasks requiring visuospatial and visual memory
      abilities. METHODS: PPA patients (n=156), diagnosed using current criteria, and
      controls were tested on a battery of tests tapping different aspects of
      visuospatial cognition. We compared the groups on an overall visuospatial factor;
      construction, immediate recall, delayed recall, and executive functioning
      composites; and on individual tests. Cross-sectional and longitudinal comparisons
      were made, adjusted for disease severity, age, and education. RESULTS: The
      logopenic variant had significantly lower scores on the visuospatial factor and
      the most impaired scores on all composites. The nonfluent variant had significant
      difficulty on all visuospatial composites except the delayed recall, which
      differentiated them from the logopenic variant. In contrast, the semantic
      variants performed poorly only on delayed recall of visual information. The
      logopenic and nonfluent variants showed decline in figure copying performance
      over time, whereas in the semantic variant, this skill was remarkably preserved.
      CONCLUSIONS: This extensive examination of performance on visuospatial tasks in
      the PPA variants solidifies some previous findings, for example, delayed recall
      of visual stimuli adds value in differential diagnosis between logopenic variant
      PPA and nonfluent variant PPA variants, and illuminates the possibility of common
      mechanisms that underlie both linguistic and non-linguistic deficits in the
      variants. Furthermore, this is the first study that has investigated visuospatial
      functioning over time in the PPA variants. (JINS, 2018, 24, 259-268).

PMID- 29039276
TI  - Sinus of Valsalva aneurysm rupture in an infant.
AB  - We present the case of a 10-month-old female with a right coronary sinus of
      Valsalva aneurysm with rupture into the right atrial appendage who presented with
      a murmur. Surgical repair was performed shortly after diagnosis with pericardial
      patch closure from within the aorta and closure of the right atrial rupture site.
      To our knowledge, this is the youngest child with sinus of Valsalva aneurysm with
      rupture to be identified in the literature.

PMID- 29039277
TI  - Is paliperidone palmitate more effective than other long-acting injectable
      antipsychotics?
AB  - BACKGROUND: Paliperidone palmitate is one of the most widely prescribed long
      acting injectable (LAI) antipsychotics in the UK. However, it is relatively
      expensive and there are few data comparing its effectiveness to that of other LAI
      antipsychotics. We sought to address this issue by analyzing a large anonymized
      electronic health record (EHR) dataset from patients treated with LAI
      antipsychotics. METHODS: EHR data were obtained from 1281 patients in the South
      London and Maudsley NHS Foundation Trust (SLaM) who started treatment with a LAI
      antipsychotic between 1 April 2011 and 31 January 2015. The number of days spent
      as a psychiatric inpatient and the number of admissions to a psychiatric hospital
      were analyzed in each of the 3 years before and after LAI prescription. RESULTS:
      Patients treated with paliperidone palmitate (n = 430; 33.6%) had a greater
      number of inpatient days and a greater number of admissions in the year prior to
      treatment than those treated with other LAI antipsychotics. Nevertheless, in the
      3 years after initiation there were no significant differences between
      paliperidone and the other LAI antipsychotics in the number of days as an
      inpatient (B coefficient 5.4 days, 95% confidence interval (CI) -57.3 to 68.2, p
      = 0.86) or number of hospital admissions (Incidence rate ratio 1.07, 95% CI 0.62
      to 1.83, p = 0.82). CONCLUSION: Paliperidone palmitate was more likely to be
      prescribed in patients with more frequent and lengthy hospital admissions prior
      to initiation. However, the absence of differences in outcomes after initiation
      indicates that paliperidone palmitate was not more effective than other cheaper
      LAI antipsychotics.

PMID- 29039278
TI  - Genetic correlations among milk yield, morphology, performance test traits and
      somatic cells in dual-purpose Rendena breed.
AB  - Selection in native local breeds needs great carefulness due to the small
      population size and the risk of inbreeding. Furthermore, most breeds are dual
      purpose, and milk and beef attitudes are antagonistic. For preservation purposes
      functional traits need to be considered. Focusing on the small local Rendena
      cattle, this study aimed to analyse the genetic correlations among milk, beef and
      udder health traits and the response to selection predicted under different
      scenarios. The study considered milk, fat and protein yields (MY), factor scores
      for udder volume (UV), conformation (UC) and muscularity obtained from type
      traits scored on primiparous cows, and performance test traits (PT) measured on
      young bulls at test station: average daily gain, in vivo SEUROP fleshiness, in
      vivo dressing percentage. Somatic cell score (SCS) was considered as a functional
      trait, with a possibility of restricting its genetic gain to zero. The study
      considered 281 497 MY test-day data collected on 16 974 cows, and data from
      linear type evaluation on 11 992 primiparous cows for factor scores. The PT data
      were recorded on 1428 young bulls, and SCS obtained from cell counts at milk
      recording. Bi-trait restricted maximum likelihood animal model analyses were
      performed to assess genetic parameters. Heritability varied from 0.157 (fat) to
      0.442 (dressing percentage). Udder volume and MY resulted positively genetically
      correlated (average correlation 0.427), whereas the low-negative genetic
      correlation between MY and UC (-0.141) suggested a negative impact of milk gain
      on udder form. Beef traits of factor muscularity and PT showed medium-high
      favourable genetic correlations (from 0.357 to 0.984), excluding a null
      correlation between daily gain and muscularity. The genetic correlation MY v.
      muscularity was unfavourable (-0.328 on average), whereas null correlations were
      found in MY v. PT, apart from fat v. dressing percentage (-0.151). Somatic cell
      score showed low unfavourable correlations with protein (0.111) and UV (0.092),
      and favourable correlations with UC (-0.193). Response to selection in different
      scenarios indicated a good balanced gain for milk and beef when standardized
      economic weights of 0.66 and 0.34 are given to the two attitudes, and SCS genetic
      gain is restricted. Current genetic trends (MY and PT increasing, but muscularity
      lessening) reflect a stronger selection for milk, suggesting a slight progressive
      change towards a milk conformation. Aiming to preserve the dual-purpose
      characteristics of a breed, proper breeding policies taking into account the
      genetic relationships among traits and including functional traits should be
      applied in local dual-purpose populations.

PMID- 29039279
TI  - Estimation of the frequency of Q fever in sheep, goat and cattle herds in France:
      results of a 3-year study of the seroprevalence of Q fever and excretion level of
      Coxiella burnetii in abortive episodes.
AB  - A study was carried out, from 2012 to 2015, in 10 French departements to estimate
      the serological prevalence of Q fever and the frequency of abortive episodes
      potentially related to Coxiella burnetii in a large sample of cattle, sheep and
      goat herds. The serological survey covered 731 cattle, 522 sheep and 349 goat
      herds, randomly sampled. The frequency of abortive episodes potentially related
      to C. burnetii was estimated by investigating series of abortions in 2695 cattle,
      658 sheep and 105 goat herds using quantitative polymerase chain reaction
      analyses and complementary serological results when needed. The average between
      herd seroprevalence was significantly lower for cattle (36.0%) than for sheep
      (55.7%) and goats (61.0%) and significantly higher for dairy herds (64.9% for
      cattle and 75.6% for sheep) than for meat herds (18.9% for cattle and 39.8% for
      sheep). Within-herd seroprevalence was also significantly higher for goats
      (41.5%) than for cattle (22.2%) and sheep (25.7%). During the study period, we
      estimated that 2.7% (n = 90), 6.2% (n = 48) and 16.7% (n = 19) of the abortive
      episodes investigated could be 'potentially related to C. burnetii'in cattle,
      sheep and goat herds, respectively. Overall, strong variability was observed
      between departements and species, suggesting that risk factors such as herd
      density and farming practices play a role in disease transmission and
      maintenance.

PMID- 29039280
TI  - Very long-chain n-3 fatty acids and human health: fact, fiction and the future.
AB  - EPA and DHA appear to be the most important n-3 fatty acids, but roles for n-3
      docosapentaenoic acid are now also emerging. Intakes of EPA and DHA are usually
      low, typically below those recommended. Increased intakes result in higher
      concentrations of EPA and DHA in blood lipids, cells and tissues. Increased
      content of EPA and DHA modifies the structure of cell membranes and the function
      of membrane proteins. EPA and DHA modulate the production of lipid mediators and
      through effects on cell signalling can alter the patterns of gene expression.
      Through these mechanisms, EPA and DHA alter cell and tissue responsiveness in a
      way that often results in more optimal conditions for growth, development and
      maintenance of health. DHA has vital roles in brain and eye development and
      function. EPA and DHA have a wide range of physiological roles, which are linked
      to certain health or clinical benefits, particularly related to CVD, cancer,
      inflammation and neurocognitive function. The benefits of EPA and DHA are evident
      throughout the life course. Future research will include better identification of
      the determinants of variation of responses to increased intake of EPA and DHA;
      more in-depth dose-response studies of the effects of EPA and DHA; clearer
      identification of the specific roles of EPA, docosapentaenoic acid and DHA;
      testing strategies to enhance delivery of n-3 fatty acids to the bloodstream; and
      exploration of sustainable alternatives to fish-derived very long-chain n-3 fatty
      acids.

PMID- 29039281
TI  - Inhibitory effects of an extract from non-host plants on physiological
      characteristics of two major cabbage pests.
AB  - The diamondback moth (Plutella xylostella) and small white cabbage butterfly
      (Pieris rapae) are the two main serious pests of cruciferous crops (Brassicaceae)
      that have developed resistance to chemical control methods. In order to avoid
      such resistance and also the adverse effects of chemical pesticides on the
      environment, alternative methods have usually been suggested, including the use
      of plant enzyme inhibitors. Here, the inhibitory effects of proteinaceous
      inhibitors extracted from wheat, canola, sesame, bean and triticale were
      evaluated against the digestive alpha-amylases, larval growth, development and
      nutritional indecs of the diamondback moth and small white cabbage butterfly. Our
      results indicated that triticale and wheat extracts inhibited alpha-amylolytic
      activity in an alkaline pH, which is in accordance with the moth and butterfly
      gut alpha-amylase optimum pH. Dose-dependent inhibition of two crucifer pests by
      triticale and wheat was observed using spectrophotometry and gel electrophoresis.
      Implementation of specificity studies showed that wheat and triticale
      proteinaceous extract were inactive against Chinese and purple cabbage amylase.
      Triticale and wheat were resistant against insects' gut proteases. Results of the
      feeding bioassay indicated that triticale-proteinaceous extract could cause a
      significant reduction in survival and larval body mass. The results of the
      nutritional indecs also showed larvae of both species that fed on a Triticale
      proteinaceous inhibitor-treated diet had the lowest values for the efficiency of
      conversion of ingested food and relative growth rate. Our observations suggested
      that triticale shows promise for use in the management of crucifer pests.

PMID- 29039282
TI  - Spatial variation of pneumonia hospitalization risk in Twin Cities metro area,
      Minnesota.
AB  - Fine resolution spatial variability in pneumonia hospitalization may identify
      correlates with socioeconomic, demographic and environmental factors. We
      performed a retrospective study within the Fairview Health System network of
      Minnesota. Patients 2 months of age and older hospitalized with pneumonia between
      2011 and 2015 were geocoded to their census block group, and pneumonia
      hospitalization risk was analyzed in relation to socioeconomic, demographic and
      environmental factors. Spatial analyses were performed using Esri's ArcGIS
      software, and multivariate Poisson regression was used. Hospital encounters of 17
      840 patients were included in the analysis. Multivariate Poisson regression
      identified several significant associations, including a 40% increased risk of
      pneumonia hospitalization among census block groups with large, compared with
      small, populations of ?65 years, a 56% increased risk among census block groups
      in the bottom (first) quartile of median household income compared to the top
      (fourth) quartile, a 44% higher risk in the fourth quartile of average nitrogen
      dioxide emissions compared with the first quartile, and a 47% higher risk in the
      fourth quartile of average annual solar insolation compared to the first
      quartile. After adjusting for income, moving from the first to the second
      quartile of the race/ethnic diversity index resulted in a 21% significantly
      increased risk of pneumonia hospitalization. In conclusion, the risk of pneumonia
      hospitalization at the census-block level is associated with age, income,
      race/ethnic diversity index, air quality, and solar insolation, and varies by
      region-specific factors. Identifying correlates using fine spatial analysis
      provides opportunities for targeted prevention and control.

PMID- 29039283
TI  - Effects of between-person differences and within-person changes in symptoms of
      anxiety and depression on older age cognitive performance.
AB  - BACKGROUND: Anxiety and depression are both important correlates of cognitive
      function. However, longitudinal studies investigating how they covary with
      cognition within the same individual are scarce. We aimed to simultaneously
      estimate associations of between-person differences and within-person variability
      in anxiety and depression with cognitive performance in a sample of non-demented
      older people. METHODS: Participants in the Lothian Birth Cohort 1921 study, a
      population-based narrow-age sample (mean age at wave 1 = 79 years, n = 535), were
      examined on five occasions across 13 years. Anxiety and depression were measured
      with the Hospital Anxiety and Depression Scale (HADS) and cognitive performance
      was assessed with tests of reasoning, logical memory, and letter fluency. Data
      were analyzed using two-level linear mixed-effects models with within-person
      centering. RESULTS: Divergent patterns were observed for anxiety and depression.
      For anxiety, between-person differences were more influential; people who scored
      higher on HADS anxiety relative to other same-aged individuals demonstrated
      poorer cognitive performance on average. For depression, on the other hand, time
      varying within-person differences were more important; scoring higher than usual
      on HADS depression was associated with poorer cognitive performance relative to
      the average level for that participant. Adjusting for gender, childhood mental
      ability, emotional stability, and disease burden attenuated these associations.
      CONCLUSIONS: The results from this study highlight the importance of addressing
      both between- and within-person effects of negative mood and suggest that anxiety
      and depression affect cognitive function in different ways. The current findings
      have implications for assessment and treatment of older age cognitive deficits.

PMID- 29039285
TI  - Prospective risk factors for post-deployment heavy drinking and alcohol or
      substance use disorder among US Army soldiers.
AB  - BACKGROUND: Investigations of drinking behavior across military deployment cycles
      are scarce, and few prospective studies have examined risk factors for post
      deployment alcohol misuse. METHODS: Prevalence of alcohol misuse was estimated
      among 4645 US Army soldiers who participated in a longitudinal survey. Assessment
      occurred 1-2 months before soldiers deployed to Afghanistan in 2012 (T0), upon
      their return to the USA (T1), 3 months later (T2), and 9 months later (T3).
      Weights-adjusted logistic regression was used to evaluate associations of
      hypothesized risk factors with post-deployment incidence and persistence of heavy
      drinking (HD) (consuming 5 + alcoholic drinks at least 1-2*/week) and alcohol or
      substance use disorder (AUD/SUD). RESULTS: Prevalence of past-month HD at T0, T2,
      and T3 was 23.3% (s.e. = 0.7%), 26.1% (s.e. = 0.8%), and 22.3% (s.e. = 0.7%);
      corresponding estimates for any binge drinking (BD) were 52.5% (s.e. = 1.0%),
      52.5% (s.e. = 1.0%), and 41.3% (s.e. = 0.9%). Greater personal life stress during
      deployment (e.g., relationship, family, or financial problems) - but not combat
      stress - was associated with new onset of HD at T2 [per standard score increase:
      adjusted odds ratio (AOR) = 1.20, 95% CI 1.06-1.35, p = 0.003]; incidence of
      AUD/SUD at T2 (AOR = 1.54, 95% CI 1.25-1.89, p < 0.0005); and persistence of
      AUD/SUD at T2 and T3 (AOR = 1.30, 95% CI 1.08-1.56, p = 0.005). Any BD pre
      deployment was associated with post-deployment onset of HD (AOR = 3.21, 95% CI
      2.57-4.02, p < 0.0005) and AUD/SUD (AOR = 1.85, 95% CI 1.27-2.70, p = 0.001).
      CONCLUSIONS: Alcohol misuse is common during the months preceding and following
      deployment. Timely intervention aimed at alleviating/managing personal stressors
      or curbing risky drinking might reduce risk of alcohol-related problems post
      deployment.

PMID- 29039284
TI  - The association between diurnal temperature range and childhood hand, foot, and
      mouth disease: a distributed lag non-linear analysis.
AB  - In recent years, hand, foot, and mouth disease (HFMD) has been increasingly
      recognized as a critical challenge to disease control and prevention in China.
      Previous studies have found that meteorological factors such as mean temperature
      and relative humidity were associated with HFMD. However, little is known about
      whether the diurnal temperature range (DTR) has any impact on HFMD. This study
      aimed to quantify the impact of DTR on childhood HFMD in 18 cities in Sichuan
      Province. A distributed lag non-linear model was adopted to explore the temporal
      lagged association of daily temperature with age-, gender- and pathogen-specific
      HFMD. A total of 290 123 HFMD cases aged 0-14 years were reported in the 18
      cities in Sichuan Province. The DTR-HFMD relationships were non-linear in all
      subgroups. Children aged 6-14 years and male children were more vulnerable to the
      temperature changes. Large DTR had the higher risk estimates of HFMD incidence in
      cases of EV71 infection, while small DTR had the higher risk estimates of HFMD
      incidence in cases of CV-A16 infection. Our study suggested that DTR played an
      important role in the transmission of HFMD with non-linear and delayed effects.

PMID- 29039286
TI  - Relationship between carcass traits, prime cuts and carcass grading from foals
      slaughtered at the age of 13 and 26 months and supplemented with standard and
      linseed-rich feed.
AB  - In order to improve foal carcass quality, it is necessary in particular to
      improve the carcass dressing percentage and tissue composition. Thus, it is
      important to establish relationships between grading systems and these
      parameters. This research was conducted to study the effect of slaughter age (13
      v. 26 months) and finishing feed (standard v. linseed feed) on carcass
      characteristics such as subcutaneous fat colour plus classification of foals for
      the degree of fatness and conformation. For this study, 46 foals of crossbred
      genotype (Galician Mountain*Burguete) were used. Finishing feed did not affect
      any parameter, whereas slaughter age influenced all parameters (P<0.05). The
      oldest foals had higher carcass measurements, 13% more of meat, 4% more of bone,
      12% more of fat, and 4% and 9% bigger fore- and hindquarter, respectively.
      Consequently, bigger valuable prime cuts were obtained. Nevertheless, the meat :
      bone ratio was very similar for both 13- and 26-month-old foals (2.88). Most of
      26-month-old foals were classified in 'E' (Extra) and '5' (Complete fat cover)
      categories of conformation and degree of fatness. Most of the carcasses showed
      subcutaneous fat described as yellowish-white irrespective of age or diet. A
      regression model found that conformation (36%) and degree of fatness (33%) in
      live animals was positively linked with carcass tissue composition. It is
      therefore suggested that producers aim for older slaughter ages than 13 months
      and that the foal meat industry establishes grading systems to predict carcass
      quality. Further studies should be necessary to find the optimal slaughter age to
      obtain carcasses in the best categories of degree of fatness and conformation.
      New studies should be recommended to improve the meat : bone ratio of foal
      carcasses as it estimates the aptitude for meat production.

PMID- 29039287
TI  - Strongyloides stercoralis seroprevalence in Vietnam.
AB  - Strongyloidiasis is a neglected tropical disease caused by the roundworm
      Strongyloides stercoralis affecting 30-100 million people worldwide. Many
      Southeast-Asian countries report a high prevalence of S. stercoralis infection,
      but there are little data from Vietnam. Here, we evaluated the seroprevalence of
      S. stercoralis related to geography, sex and age in Vietnam through serological
      testing of anonymized sera. Sera (n = 1710, 1340 adults and 270 children) from an
      anonymized age-stratified serum bank from four regions in Vietnam between 2012
      and 2013 were tested using a commercial Strongyloides ratti immunoglobulin G
      ELISA. Seroreactivity was found in 29.1% (390/1340) of adults and 5.5% (15/270)
      of children. Male adults were more frequently seroreactive than females (33.3%
      vs. 24.9%, P = 0.001). The rural central highlands had the highest seroprevalence
      (42.4% of adults). Seroreactivity in the other regions was 29.9% (Hue) and 26.0%
      and 18.2% in the large urban centres of Hanoi and Ho Chi Minh City, respectively.
      We conclude that seroprevalence of S. stercoralis was high in the Vietnamese
      adult population, especially in rural areas.

PMID- 29039288
TI  - Molecular and morphological characterization of Belondira coomansi n. sp.
      (Nematoda: Dorylaimida, Belondiridae) from Iran.
AB  - A new species belonging to the genus Belondira is described from natural areas in
      Iran. Belondira coomansi n. sp. is characterized by its general size, the
      dimensions and appearance of its lip region, presence of distinct labial and post
      labial sclerotization, the length of the odontostyle and its inconspicuous lumen
      and aperture, the length of the neck and its pharyngeal expansion, the reduction
      of the female anterior genital branch to a simple uterine sac, a very short
      posterior uterus, the anterior position of the vulva, the length and shape of the
      caudal region with distinctly thick cuticle at its tip, the length of the
      spicules, and the presence of only one pair of ventromedian supplements. The new
      species is close to Belondira brevibulba, B. sacchari, B. tenuidens and B.
      thornei, and it is compared to them. Molecular characterization (D2-D3 expansion
      segments of the rRNA large subunit) of the new species is also provided,
      representing only the second species of this genus for which any DNA sequence
      data are available.

PMID- 29039289
TI  - Death by suicide at the Ward level in Northern Ireland.
AB  - BACKGROUND: Deaths from suicide, as recorded within the Northern Ireland
      Coroner's Office for the years 2005-2011 inclusive, were analysed in terms of
      standardised mortality ratios (SMRs), within Wards and Local Government Districts
      (LGDs). The aim of the study is to examine factors relating to the ecological
      context of the area within which the person resided at time of death. Area
      deprivation, religious composition and age structure are examined in terms of
      SMRs, while controlling for the number of individuals living within a designated
      area. METHODS: Random-intercept Poisson regression models were used in
      conjunction with empirical Bayes prediction to examine area effects. RESULTS:
      Considerable variation occurs between the numbers of recorded deaths within each
      area. A strong association is shown between deprivation and the number of deaths
      by suicide within an area. There was considerable variation at the LGD level in
      terms of the number of deaths, but once the nested nature of Wards was taken into
      account and adjusted for level of deprivation, the variation between LGD was no
      longer statistically significant. When adjusted for the number of individuals
      within each age group, the number of deaths in the younger and middle-aged groups
      did not show a statistical difference (0.05 level), nor did the religious
      composition of the area in terms of the number of recorded deaths. CONCLUSIONS:
      Based on SMRs, using empirical Bayes prediction, area effects were shown to be
      substantial, especially in urban locations where there are high rates of
      deprivation.

PMID- 29039290
TI  - Simulated-Use Polytetrafluorethylene Biofilm Model: Repeated Rounds of Complete
      Reprocessing Lead to Accumulation of Organic Debris and Viable Bacteria.
AB  - OBJECTIVE Biofilm has been implicated in bacterial persistence and survival after
      endoscope reprocessing. In this study, we assessed the impact of different
      methods of reprocessing on organic residues and viable bacteria after repeated
      rounds of biofilm formation when each was followed by full reprocessing. METHODS
      ATS-2015, an artificial test soil containing 5-8 Log10 colony-forming units (CFU)
      of Enterococcus faecalis and Pseudomonas aeruginosa, was used to form biofilm in
      polytetrafluroethylene channels overnight on 5 successive days. Each successive
      day, full pump-assisted cleaning using bristle brushes or pull-through devices in
      combination with enzymatic or nonenzymatic detergents followed by fully automated
      endoscope reprocessor disinfection using peracetic acid was performed. Residuals
      were visualized by scanning electron microscopy (SEM). Destructive testing was
      used to assess expected cutoffs for adenosine triphosphate (ATP; <200 relative
      light units), protein (<2 ug/cm2), and viable bacteria count (0 CFU). RESULTS
      Protein residuals were above 2 ug/cm2, but ATP residuals were <200 relative light
      units for all methods tested. Only when enzymatic cleaner was used for cleaning
      were there no viable bacteria detected after disinfection irrespective of whether
      bristle brushes or pull-through devices were used. SEM revealed that some
      residual debris remained after all reprocessing methods, but more residuals were
      detected when a nonenzymatic detergent was used. CONCLUSIONS Surviving E.
      faecalis and P. aeruginosa were only detected when the non-enzymatic detergent
      was used, emphasizing the importance of the detergent used for endoscope channel
      reprocessing. Preventing biofilm formation is critical because not all current
      reprocessing methods can reliably eliminate viable bacteria within the biofilm
      matrix. Infect Control Hosp Epidemiol 2017;38:1284-1290.

PMID- 29039291
TI  - Asset Literacy Following Stroke: Implications for Disaster Resilience.
AB  - OBJECTIVE: The World Stroke Organization "1 in 6" campaign aims to raise
      awareness that 1 in 6 persons will experience a stroke during their lifetime.
      With aging populations and improved survival rates, an increased number of
      survivors live with functional limitations and require supportive care. This has
      important implications for implementing an all-of-society approach to disaster
      risk reduction. In this study, we explore the assets that stroke survivors and
      caregivers consider useful in supporting their capacity to manage routine
      activities and independent living and to respond to a disaster. METHODS:
      Transcripts from interviews with stroke survivors and caregivers were analyzed by
      use of content analysis. RESULTS: Assets were categorized into 4 classes: social,
      physical, energy, and personal characteristics and are presented as a household
      map. Emergent themes suggested that understanding how to mobilize assets is
      complicated yet essential for building resilience. Household resilience requires
      people have self-efficacy and motivation to move from awareness to action. The
      findings informed development of a conceptual model of asset literacy and
      household resilience following stroke. CONCLUSIONS: Interventions to enhance
      asset literacy can support an all-of-society approach to disaster risk reduction
      through awareness, empowerment, participation, innovation, and engagement.
      (Disaster Med Public Health Preparedness. 2018; 12: 312-320).

PMID- 29039292
TI  - An innovative short-stay health care model for treatment of uncomplicated vaso
      occlusive crisis in adult sickle cell disease patients in Canada to reduce
      emergency department utilization.
AB  - OBJECTIVES: Patients with sickle cell disease (SCD) with vaso-occlusive crises
      (VOC) often visit the emergency department (ED) for management of painful
      episodes. The primary objective of this pilot study was to evaluate the
      acceptability of a short-stay model for treatment of VOC in SCD outside of the ED
      in Toronto, Canada. Secondary objectives were to assess patient satisfaction of
      this model, barriers to its use and comparison of clinical outcomes to a
      historical control. METHODS: Adult SCD patients with symptoms of an uncomplicated
      VOC between October 2014 to July 2016 were managed according to best practice
      recommendations in a short-stay unit as an alternative to the local emergency
      room. Primary outcome of time to first analgesia, and secondary outcome of
      discharge rate were compared to a historical control at a local ED from 2009
      2012. Satisfaction and barriers to use of the ambulatory care delivery model were
      assessed by patient survey. RESULTS: Twenty-one visits were recorded at the short
      stay unit during the study period. Average time to first opiate dose was 23.5
      minutes in the short-stay unit compared to 100.3 minutes in the ED (p<0.001).
      Discharge rate from the short-stay unit was 84.2%. Average patient satisfaction
      with this model of care was high (>4/5 on Likert scale) except for geographic
      accessibility (85% response rate, n=18). CONCLUSION: This study demonstrated high
      patient satisfaction and acceptability of a short-stay model for treatment of
      uncomplicated VOC in adult SCD patients in Toronto, the first of its kind in
      Canada.

PMID- 29039293
TI  - Conflict and cooperation in paranoia: a large-scale behavioural experiment.
AB  - BACKGROUND: Paranoia involves thoughts and beliefs about the harmful intent of
      others but the social consequences have been much less studied. We investigated
      whether paranoia predicts maladaptive social behaviour in terms of cooperative
      and punitive behaviour using experimental game theory paradigms, and examined
      whether reduced cooperation is best explained in terms of distrust as previous
      studies have claimed. METHODS: We recruited a large population sample (N = 2132)
      online. All participants completed the Green et al. Paranoid Thoughts Scale and
      (i) a Dictator Game and (ii) an Ultimatum Game, the former with an option for
      costly punishment. Following distrust-based accounts, we predicted highly
      paranoid people would make higher offers when the outcome depended on receiving a
      positive response from their partner (Ultimatum Game) but no difference when the
      partner's response was irrelevant (Dictator Game). We also predicted paranoia
      would increase punitive responses. Predictions were pre-registered in advance of
      data collection. Data and materials are open access. RESULTS: Highly paranoid
      participants actually made lower offers than non-paranoid participants both in
      the Dictator Game and in the Ultimatum Game. Paranoia positively predicted
      punitive responses. CONCLUSIONS: These findings suggest that distrust is not the
      best explanation for reduced cooperation in paranoia and alternative
      explanations, such as increased self-interest, may apply. However, the tendency
      to attribute harmful intent to partners was important in motivating punitive
      responses. These results highlight differing motivations underlying adverse
      social behaviour in paranoia and suggest that accounts based solely on the
      presenting features of paranoia may need to be rethought.

PMID- 29039294
TI  - A Comparison of Heritability Estimates by Classical Twin Modeling and Based on
      Genome-Wide Genetic Relatedness for Cardiac Conduction Traits.
AB  - Twin studies have found that ~50% of variance in electrocardiogram (ECG) traits
      can be explained by genetic factors. However, genetic variants identified through
      genome-wide association studies explain less than 10% of the total trait
      variability. Some have argued that the equal environment assumption for the
      classical twin model might be invalid, resulting in inflated narrow-sense
      heritability (h 2) estimates, thus explaining part of the 'missing h 2'. Genomic
      relatedness restricted maximum likelihood (GREML) estimation overcomes this
      issue. This method uses both family data and genome-wide coverage of common SNPs
      to determine the degree of relatedness between individuals to estimate both h 2
      explained by common SNPs and total h 2. The aim of the current study is to
      characterize more reliably than previously possible ECG trait h 2 using GREML
      estimation, and to compare these outcomes to those of the classical twin model.
      We analyzed ECG traits (heart rate, PR interval, QRS duration, RV5+SV1, QTc
      interval, Sokolow-Lyon product, and Cornell product) in up to 3,133 twins from
      the TwinsUK cohort and derived h 2 estimates by both methods. GREML yielded h 2
      estimates between 47% and 68%. Classical twin modeling provided similar h 2
      estimates, except for the Cornell product, for which the best fit included no
      genetic factors. We found no evidence that the classical twin model leads to
      inflated h 2 estimates. Therefore, our study confirms the validity of the equal
      environment assumption for monozygotic and dizygotic twins and supports the
      robust basis for future studies exploring genetic variants responsible for the
      variance of ECG traits.

PMID- 29039295
TI  - Effects of feeding low fishmeal diets with increasing soybean meal levels on
      growth, gut histology and plasma biochemistry of sea bass.
AB  - The aquaculture industry depends upon the development of sustainable protein
      sources to replace fishmeal (FM) in aquafeeds and the products derived from
      soybeans are some of the most studied plant feedstuffs. A key area of
      investigation for continuing to improve modern aquafeeds includes the evaluation
      of varying proportions and combinations of plant ingredients to identify mixtures
      that are more efficiently utilized by the fish. This study investigated the
      effects of increasing soybean meal (SBM) by replacing a mix of plant ingredients
      in low FM (20%) diets on growth, blood biochemistry profile and gut histology on
      European sea bass. Five isonitrogenous and isolipidic experimental diets were
      formulated: four diets containing increasing SBM levels (0, 10, 20 and 30%; 0SBM,
      10SBM, 20SBM and 30SBM, respectively) with a low content of FM (20%) and one
      control diet (0% SBM; 35% FM). Diets containing SBM brought to comparable
      performance and protein utilization, while 0SBM had negative impact on feed
      conversion rate and protein utilization. Blood parameters suggested an optimal
      nutritional status under all feeding treatments, even though slightly decreased
      values were reported at increasing dietary SBM. Histology examination did not
      show any changes indicative of soy-induced enteritis. We can conclude that for
      European sea bass: (i) different blends of plant protein did not affect feed
      intake despite the 20% FM dietary level; (ii) the inclusion of SBM maintains
      optimal growth and feed utilization in low FM diets; (iii) blood biochemistry
      profile showed a good nutritional status under all feeding regimes; (iv) no
      evidence of soy-induced enteritis was reported in any group fed low FM diets. For
      formulation of practical diets in on-growing of European sea bass, SBM up to 30%
      can be successfully incorporated into feeds containing low FM inclusion.

PMID- 29039296
TI  - Effect of human milk formula with bovine colostrum supplementation on bone
      mineral density in infant cynomolgus macaques.
AB  - Insulin-like growth factor 1 (IGF1) is a regulator of human growth during infancy
      and childhood, known to promote bone and muscle growth as well as lipid
      accumulation. This study aimed to investigate the effects of formula milk with or
      without IGF1 supplementation (in the form of pure IGF1 or bovine colostrum) on
      growth and body composition in infant cynomolgus macaques during the first 6
      months of life. Three groups of infants were nursery-reared and received formula
      milk with or without IGF1 or bovine colostrum supplementation for 4 months, and a
      fourth group consisting of breast-fed infants was included for comparison (n=6
      for each group). Ranked-based analysis of covariance was used to detect
      differences between adjusted means for sex. No differences in weight, height, fat
      mass, and fat-free mass could be detected between groups. However, bone mineral
      density (BMD) was significantly different between groups at the end of formula
      feeding. Infants that received bovine colostrum supplementation displayed higher
      mean BMD than infants of all other groups, with no differences between the latter
      three groups. In conclusion, our results suggest that supplementation with bovine
      colostrum can enhance BMD in formula-fed infants, an effect that apparently does
      not depend on IGF1. Bovine colostrum supplementation could be beneficial for long
      term bone health in infants with suboptimal bone growth.

PMID- 29039297
TI  - The impact of periconceptional alcohol exposure on fat preference and gene
      expression in the mesolimbic reward pathway in adult rat offspring.
AB  - Alcohol consumption around the time of conception is highly prevalent in Western
      countries. Exposure to ethanol levels during gestation has been associated with
      altered development of the mesolimbic reward pathway in rats and increased
      propensity to addiction, however the effect of exposure only around the time of
      conception is unknown. The current study investigated the effects of
      periconceptional alcohol exposure (PC:EtOH) on alcohol and palatable food
      preferences and gene expression in the ventral tegmental area (VTA) and the
      nucleus accumbens of the adult offspring. Rats were exposed to a liquid diet
      containing ethanol (EtOH) (12.5% vol/vol) or a control diet from 4 days before
      mating until 4 days after mating. PC:EtOH had no effect on alcohol preference in
      either sex. At 15 months of age, however, male PC:EtOH offspring consumed more
      high-fat food when compared with male control offspring, but this preference was
      not observed in females. Expression of the dopamine receptor type 1 (Drd1a) was
      lower in the VTA of male PC:EtOH offspring compared with their control
      counterparts. There was no effect of PC:EtOH on mRNA expression of the u-opioid
      receptor, tyrosine hydroxylase (Th), dopamine receptor type 2 (Drd2) or dopamine
      active transporter (Slc6a3). These data support the hypothesis that
      periconceptional alcohol exposure can alter expression of key components of the
      mesolimbic reward pathway and heighten the preference of offspring for palatable
      foods and may therefore increase their propensity towards diet-induced obesity.
      These results highlight the importance of alcohol avoidance when planning a
      pregnancy.

PMID- 29039298
TI  - Application of bioelectrical impedance analysis in prediction of light kid
      carcass and muscle chemical composition.
AB  - Carcass data were collected from 24 kids (average live weight of 12.5+/-5.5 kg;
      range 4.5 to 22.4 kg) of Jarmelista Portuguese native breed, to evaluate
      bioelectrical impedance analysis (BIA) as a technique for prediction of light kid
      carcass and muscle chemical composition. Resistance (Rs, Omega) and reactance
      (Xc, Omega), were measured in the cold carcasses with a single frequency
      bioelectrical impedance analyzer and, together with impedance (Z, Omega), two
      electrical volume measurements (VolA and VolB, cm2/Omega), carcass cold weight
      (CCW), carcass compactness and several carcass linear measurements were fitted as
      independent variables to predict carcass composition by stepwise regression
      analysis. The amount of variation explained by VolA and VolB only reached a
      significant level (P<0.01 and P<0.05, respectively) for muscle weight, moisture,
      protein and fat-free soft tissue content, even so with low accuracy, with VolA
      providing the best results (0.326?R 2?0.366). Quite differently, individual BIA
      parameters (Rs, Xc and Z) explained a very large amount of variation in
      dissectible carcass fat weight (0.814?R 2?0.862; P<0.01). These individual BIA
      parameters also explained a large amount of variation in subcutaneous and
      intermuscular fat weights (respectively 0.749?R 2?0.793 and 0.718?R 2?0.760;
      P<0.01), and in muscle chemical fat weight (0.663?R 2?0.684; P<0.01). Still
      significant but much lower was the variation in muscle, moisture, protein and fat
      free soft tissue weights (0.344?R 2?0.393; P<0.01) explained by BIA parameters.
      Still, the best models for estimation of muscle, moisture, protein and fat-free
      soft tissue weights included Rs in addition to CCW, and accounted for 97.1% to
      99.8% (P<0.01) of the variation observed, with CCW by itself accounting for 97.0%
      to 99.6% (P<0.01) of that variation. Resistance was the only independent variable
      selected for the best model predicting subcutaneous fat weight. It was also
      selected for the best models predicting carcass fat weight (combined with carcass
      length, CL; R 2=0.943; P<0.01) and intermuscular fat weight (combined with CCW; R
      2=0.945; P<0.01). The best model predicting muscle chemical fat weight combined
      CCW and Z, explaining 85.6% (P<0.01) of the variation observed. These results
      indicate BIA as a useful tool for prediction of light kids' carcass composition.

PMID- 29039299
TI  - Factors associated with passive immunity transfer in dairy calves: combined
      effect of delivery time, amount and quality of the first colostrum meal.
AB  - Despite the well-known importance of an adequate colostral immunoglobulin (Ig)
      transfer to calf health and survival, failed transfer of passive immunity (FTPI)
      remains a widespread problem in dairy farming. The aim of this study was to
      investigate the management factors associated with FTPI in newborn calves,
      evaluating particularly the combined effect of delivery time, amount and quality
      of the first colostrum meal. The study was conducted from March to August 2014 on
      21 Italian dairy farms. Farmers were asked as first to answer a farm-level
      questionnaire on calf management. Blood sampling was then performed on overall
      244 calves (1 to 5 days of age) born from Holstein cows, and a sample of the
      first colostrum meal of each calf was collected. Individual information on calves
      and the respective colostrum management were recorded. Serum and colostrum Ig
      concentrations were assessed by electrophoresis. A mixed effects multivariable
      logistic regression model was used to investigate the association of the
      variables obtained from both the management questionnaire and the individual calf
      data with FTPI (calf serum Ig concentration 87.6 g/l) within 1.0 h from birth.
      Considerable improvements are still needed about colostrum management for newborn
      calves in dairy farms. The results of this study will help in developing farm
      specific programs for reducing the occurrence of FTPI.

PMID- 29039300
TI  - Disaster Preparedness of Child Care Teachers: A Cross-Sectional Study in South
      Korea.
AB  - OBJECTIVE: We aimed to identify the differences in personal disaster preparedness
      and disaster risk perception among child care and preschool teachers in South
      Korea by using demographic characteristics and disaster-related questions.
      METHODS: A cross-sectional self-reporting questionnaire was administered from
      February to October 2014. RESULTS: Of all the participants, 68.1% had received
      disaster preparedness education and training on 2 or more occasions per year;
      13.2% had received no education or training. Personal disaster preparedness
      differed significantly by marital status (P<0.05), the number of disaster
      education and training sessions attended (P<0.05), and having purchased home
      insurance (P<0.001). Disaster risk perception differed significantly by
      children's age group under a teacher's care (P<0.05). The topic on which child
      care teachers wanted more training was "fractures and bleeding emergency care"
      (53.9%). The most probable disaster was considered to be a typhoon (66.0%).
      CONCLUSIONS: Disaster preparedness is important for both young children and their
      teachers. Field-based teacher disaster preparedness education and training should
      be provided so that they can respond effectively to disaster occurrence
      regardless of type, time, or location. (Disaster Med Public Health Preparedness.
      2018; 12: 321-328).

PMID- 29039301
TI  - Populational and individual perspective on needs.

PMID- 29039302
TI  - OXA-48 and CTX-M-15 extended-spectrum beta-lactamases in raw milk in Lebanon:
      epidemic spread of dominant Klebsiella pneumoniae clones.
AB  - Raw milk has recently been reported as a source of extended-spectrum beta
      lactamase (ESBL) and carbapenemase genes. We thus investigated the prevalence of
      ESBL- and carbapenemase-producing Enterobacteriaceae in raw milk in Lebanon in
      order to assess the risk of transfer of these bacteria to humans. A high
      prevalence (30.2 %) of CTX-M-15-producing K. pneumoniae was detected in raw
      bovine milk. Three main K. pneumoniae clones were identified by PFGE and MLST
      typing. Southern blot experiments revealed that one of these clones carried the
      blaCTX-M-15 gene chromosomally. Moreover, one OXA-48-producing K. pneumoniae
      ST530 and seven CTX-M-15-producing Escherichia coli sharing the same ST were also
      detected. These findings highlight the spread of dominant CTX-M-15-producing K.
      pneumoniae clones and OXA-48-producing isolates in the food chain. Milk, which is
      mostly consumed raw in Lebanon, may be a source of human exposure to ESBLs and
      carbapenemases.

PMID- 29039303
TI  - Paraferrimonas haliotis sp. nov., isolated from the intestine of abalone,
      Haliotis discus hannai and emendation of description of the genus Paraferrimonas.
AB  - Two strains, AFRC7-2-1T and CFD7-4-2, were isolated from the intestine of
      abalone, Haliotis discus hannai. The bacterial cells were Gram-stain-negative,
      stick-shaped and non-flagellated. They were facultative anaerobic bacteria and
      could reduce Fe(III) to Fe(II). The 16S rRNA genes of two strains shared 99.7 %
      sequence similarity, and had the highest similarity of 97.3-97.5 % with
      Paraferrimonas sedimenticola NBRC 101628T, and of <94.0 % with other species.
      Phylogenetic relationship showed that the two strains formed a tight clade with
      an isolate Paraferrimonas sp. CGB11 obtained from the intestine of small abalone,
      H. diversicolor, and P. sedimenticola NBRC 101628T. The resulted DNA-DNA
      hybridization (DDH) values of strains AFRC7-2-1T and CFD7-4-2 compared with P.
      sedimenticola NBRC 101628T was 18.8-18.9 %. The resultant average nucleotide
      identity (ANI) values of AFRC7-2-1T and CFD7-4-2 compared with P. sedimenticola
      NBRC 101628T was 71.3-71.5 %. The predominant fatty acids (>5 %) of strains AFRC7
      2-1T and CFD7-4-2 were iso-C15 : 0, iso-C13 : 0, C14 : 0, C16 : 0, C17 : 1omega8c
      and summed feature 3 (C16 : 1omega7c/C16 : 1omega6c). The quinone system of
      strains AFRC7-2-1T and CFD7-4-2 were quinone-8, menaquinone-6, menaquinone-7, and
      quinone-7. The predominant polar lipids of strain AFRC7-2-1T were identified as
      phosphatidylethanolamine (PE), phosphatidylglycerol (PG), one unidentified
      phospholipid (PL), and three minor unidentified lipids (Ls). The genomic DNA G+C
      contents of two strains were 47.2 mol%. In summary, the two strains represented a
      novel species of the genus Paraferrimonas, for which the name Paraferrimonas
      haliotis sp. nov. was proposed, with type strain AFRC7-2-1T (=MCCC 1A11748T=KCTC
      52632T=NBRC 112785T) and strain CFD7-4-2 (=MCCC 1A11749=KCTC 52631=NBRC 112786).

PMID- 29039304
TI  - Desulfonatronum parangueonense sp. nov., a sulfate-reducing bacterium isolated
      from sediment of an alkaline crater lake.
AB  - Novel Gram-stain-negative, non-spore-forming, vibrio-shaped, anaerobic,
      alkaliphilic, sulfate-reducing bacteria, designated strains PAR180T and PAR190,
      were isolated from sediments collected at an alkaline crater lake in Guanajuato
      (Mexico). Strain PAR180T grew at temperatures between 15 and 40  degrees C
      (optimum 35  degrees C), and at pH between 8.3 and 10.4 (optimum 9). It was
      halotolerant, growing with up to 8 % (w/v) NaCl. Lactate, formate, pyruvate and
      ethanol were used as electron donors in the presence of sulfate and were
      incompletely oxidized to acetate and CO2. The isolate was able to grow with
      hydrogen and with CO2 as a carbon source. Beside sulfate, sulfite and thiosulfate
      were used as terminal electron acceptors. The isolate was able to grow by
      disproportionation of sulfite and thiosulfate, but not elemental sulfur, using
      acetate as a carbon source. The predominant fatty acids were C16 : 0, C16 :
      1omega7c and summed feature 10 (C18 : 1omega7c and/or C18 : 1omega9t and/or C18 :
      1omega12t). The DNA G+C content was 56.1 mol%. Phylogenetic analysis based on 16S
      rRNA gene sequences showed that it belongs to the genus Desulfonatronum, class
      Deltaproteobacteria. Its closest relative is Desulfonatronum thiosulfatophilum
      (98.7 % 16S rRNA gene sequence similarity). The DNA-DNA relatedness value between
      strain PAR180T and the type strain of D. thiosulfatophilum was 37.1+/-2.5 %. On
      the basis of phylogenetic, phenotypic and chemotaxonomic characteristics, the
      isolates is considered to represent a novel species of the genus Desulfonatronum,
      for which the name Desulfonatronum parangueonense sp. nov. is proposed. The type
      strain is PAR180T (=DSM 103602T=JCM 31598T).

PMID- 29039305
TI  - Changing epidemiology of Pneumocystis pneumonia, Northern Ireland, UK and
      implications for prevention, 1 July 2011-31 July 2012.
AB  - PURPOSE: There is a lack of consensus about which non-human immunodeficiency
      virus (HIV) patient groups would benefit from prophylaxis. Here, we analysed an
      enhanced Pneumocystis jirovecii database to describe the epidemiology of
      Pneumocystis pneumonia (PCP) and P. jirovecii colonizations in Northern Ireland
      (NI) with a view to identifying risk groups who may benefit from prophylaxis.
      METHODOLOGY: We prospectively collected information on demographics, clinical
      severity and clinical features for all hospital inpatients in NI aged >=18 years
      with P. jirovecii confirmed in any respiratory tract sample. We defined P.
      jirovecii colonization or PCP according to clinical symptoms and radiological
      findings. We compared P. jirovecii colonization to PCP using exact logistic
      regression and presented the odds ratios (OR), 95 % confidence intervals (CI) and
      likelihood ratio test P-values.Results/Key findings. Overall, 36/49 (73 %) of P.
      jirovecii detections were categorized as PCP. A total of 28/36 (78 %) were in non
      HIV patients, of which 18 (64 %) had cancer. The odds of PCP compared to P.
      jirovecii colonization were eight times higher in those with current exposure to
      chemotherapy (OR 8.73; 95 % CI 0.84, infinity), 16 times higher for those
      diagnosed with HIV (OR 16.2; 95 % CI 1.71, infinity) and 12 times higher for
      those ever exposed to another immunosuppressive drug (OR 12.1; 95 % CI 1.94,
      infinity). CONCLUSION: The greatest burden of PCP is now in the non-HIV group,
      particularly cancer patients. We recommend increasing clinician awareness of PCP
      risk and strengthening prevention guidelines in non-HIV patients, and promoting
      the consideration of prophylaxis on a case-by-case basis.

PMID- 29039306
TI  - Paenibacillus azotifigens sp. nov., a novel nitrogen-fixing bacterium isolated
      from paddy soil.
AB  - A nitrogen-fixing bacterium, designated NF2-4-5T, was isolated from a paddy soil
      in Anseong City, Korea. Cells of strain NF2-4-5T were Gram-staining-positive,
      motile rods and aerobic. Phylogenetic analysis based on 16S rRNA gene sequence
      comparison revealed that the strain formed a distinct lineage within the genus
      Paenibacillus and was closely related to Paenibacillus graminis RSA19T (98.7 %),
      Paenibacillus jilunlii Be17T (98.6 %), Paenibacillus salinicaeni LAM0A28T (98.6
      %) and Paenibacillus riograndensis SBR5T (98.6 %). Growth of strain NF2-4-5T
      occurs at temperatures of 18-37  degrees C, at pH 6.0-8.5 and between 0.5% and 2
      % NaCl (w/v). The only respiratory quinone was MK-7. The cell wall peptidoglycan
      of strain NF2-4-5T contained meso-diaminopimelic acid. The main cellular fatty
      acids were C16 : 0 and anteiso-C15 : 0. The major polar lipids were
      diphosphatidylglycerol (DPG), phosphatidylglycerol (PG) and
      phosphatidylethanolamine (PE). The DNA G+C content was 56.36 mol%. The DNA-DNA
      hybridization relatedness between strain NF2-4-5T and four reference strains,
      Paenibacillus graminis RSA19T, Paenibacillus jilunlii Be17T, Paenibacillus sonchi
      X19-5T and Paenibacillus riograndensis SBR5T, was 22.0+/-0.3, 20.1+/-0.7, 18.3+/
      0.3 and 12.6+/-0.5 %, respectively. The phenotypic, phylogenetic and
      chemotaxonomic results indicate that the strain NF2-4-5T represents a novel
      species of the genus Paenibacillus, for which the name Paenibacillus azotifigens
      sp. nov. is proposed. The type strain is NF2-4-5T (=KACC 18967T=LMG 29963T).

PMID- 29039307
TI  - Monoglobus pectinilyticus gen. nov., sp. nov., a pectinolytic bacterium isolated
      from human faeces.
AB  - A novel anaerobic pectinolytic bacterium (strain 14T) was isolated from human
      faeces. Phylogenetic analysis based on 16S rRNA gene sequences revealed that
      strain 14T belonged to the family Ruminococcaceae, but was located separately
      from known clostridial clusters within the taxon. The closest cultured relative
      of strain 14T was Acetivibrio cellulolyticus (89.7 % sequence similarity). Strain
      14T shared ~99 % sequence similarity with cloned 16S rRNA gene sequences from
      uncultured bacteria derived from the human gut. Cells were Gram-stain-positive,
      non-motile cocci approximately 0.6 um in diameter. Strain 14T fermented pectins
      from citrus peel, apple, and kiwifruit as well as carbohydrates that are
      constituents of pectins and hemicellulose, such as galacturonic acid, xylose, and
      arabinose. TEM images of strain 14T, cultured in association with plant tissues,
      suggested extracellular fibrolytic activity associated with the bacterial cells,
      forming zones of degradation in the pectin-rich regions of middle lamella.
      Phylogenetic and phenotypic analysis supported the differentiation of strain 14T
      as a novel genus in the family Ruminococcaceae. The name Monoglobus
      pectinilyticus gen. nov., sp. nov. is proposed; the type strain is 14T (JCM
      31914T=DSM 104782T).

PMID- 29039309
TI  - Ultra-low contrast percutaneous coronary intervention in patients with severe
      chronic kidney disease.

PMID- 29039308
TI  - Actibacterium pelagium sp. nov., a novel alphaproteobacterium, and emended
      description of the genus Actibacterium.
AB  - A Gram-stain-negative, non-motile, rod-shaped bacterium, designated JN33T, was
      isolated from seawater collected from the western Pacific Ocean. Strain JN33T was
      positive for hydrolysis of aesculin and gelatin. On the basis of 16S rRNA gene
      sequence analysis, strain JN33T showed high 16S rRNA gene sequence similarity to
      Actibacterium atlanticum 22II-S11-z10T (97.3 %), A. mucosum KCTC 23349T (96.6 %)
      and A. ureilyticum LS-811T (95.7 %) and exhibited less than 97.0 % 16S rRNA gene
      sequence similarity with respect to the other type strains within the family
      Rhodobacteraceae. Phylogenetic analysis revealed that strain JN33T fell within
      the cluster of the genus Actibacterium. The average nucleotide identity and in
      silico DNA-DNA hybridization values between strain JN33T and the type strains of
      Actibacterium species were 73.1-73.8 % and 19.8-20.1 %, respectively. The sole
      respiratory quinone was ubiquinone 10 (Q-10). The principal fatty acids were
      summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c) and C16 : 0. The major
      polar lipids were phosphatidylglycerol, one unidentified phospholipid and two
      unidentified aminolipids. The DNA G+C content was 57.8 mol%. Distinctly different
      phylogenetic characteristics, chemotaxonomic differences, as well as phenotypic
      properties, revealed that strain JN33T could be differentiated from the
      Actibacterium species with validly published names. Therefore, it is proposed
      that strain JN33T represents a novel species of the genus Actibacterium, for
      which the name Actibacterium pelagium sp. nov. (type strain, JN33T=CGMCC
      1.16012T=KCTC 52653T) is proposed.

PMID- 29039310
TI  - Effect of protective devices on the radiation dose received by the brains of
      interventional cardiologists.
AB  - AIMS: This study aimed to evaluate the effectiveness of ceiling suspended
      screens, lead glasses and lead caps in reducing radiation doses to the brains of
      interventional cardiologists. METHODS AND RESULTS: Interventional procedures
      where the thorax of the patient is irradiated with different beam projections
      were modelled. The dose reduction in the white matter and hippocampus of the
      Zubal head phantom was studied for two sizes of ceiling suspended screens, two
      types of lead glasses and lead caps of surgical and hood models, which cover
      different regions of the head. Ceiling screens were the most effective, reducing
      the dose to brain tissue by 74% or even as much as 94%. The dose reduction
      provided by lead glasses varies between 10% and 17%. For the lead caps, it
      strongly depends on the model, varying from 6% (surgical) up to 68% (hood that
      also covered lower parts of the head). CONCLUSIONS: The dose to the brain can be
      reduced by using appropriate radiation protection devices. This study has shown
      that lead caps are less protective than previously described and that the best
      protection is given by ceiling suspended screens, which are widely available in
      interventional theatres.

PMID- 29039312
TI  - Left atrial appendage closure: size does matter!

PMID- 29039311
TI  - Percutaneous biventricular cardiac assist device in cardiogenic shock and
      refractory cardiac arrest.

PMID- 29039313
TI  - Transcatheter aortic valve replacement in patients with non-calcific aortic
      stenosis.
AB  - AIMS: Limited information exists describing the results of transcatheter aortic
      valve replacement (TAVR) in patients with symptomatic severe non-calcific aortic
      stenosis (AS). We aimed to compare procedural, echocardiographic, and clinical
      outcomes among patients with non-calcific AS with those of senile calcific AS
      undergoing TAVR. METHODS AND RESULTS: We retrospectively identified patients with
      non-calcific AS who received TAVR with self-expanding transcatheter heart valves
      in our centre. Clinical and echocardiographic outcomes, and post-procedural multi
      detector computed tomography (MDCT) measures were compared to those in patients
      undergoing TAVR for calcific AS. Among 136 patients, 21 patients (15.4%) with
      native leaflet thickening and minimal calcification were identified (non-calcific
      group). The patients were significantly younger in the non-calcific group (70.0
      [64.0-75.5] vs. 75.0 [69.0-78.0] years) with comparable STS-PROM scores (6.7 [4.8
      8.9] vs. 8.2 [4.8-10.9] %). Predilation was performed less frequently (42.9% vs.
      93.9%) and post-dilation more often (71.4% vs. 42.6%) in the non-calcific group.
      Both 30-day and one-year mortality were similar between groups (0% vs. 7.8% and
      0% vs. 17.6%). Rates of post-implantation paravalvular leak >=mild at six months
      (17.6% vs. 25.7%) were comparable despite lower implantation depth among non
      calcific AS patients (10.9+/-5.7 vs. 7.2+/-4.3 mm) on post-implantation MDCT.
      CONCLUSIONS: TAVR with self-expanding transcatheter heart valves appears to be
      safe and effective in patients with non-calcific AS.

PMID- 29039314
TI  - Effects of puerarin on lipopolysaccharide-induced myocardial dysfunction in
      isolated rat hearts.
AB  - Myocardial dysfunction is a serious complication induced by sepsis. Puerarin is
      an oriental medicine that possesses therapeutic benefits for cardiovascular
      diseases. The aim of this study was to evaluate the anti-myocardial dysfunction
      effects of puerarin in isolated rat hearts induced by lipopolysaccharide- and
      compare the myocardial protective effects between the different concentrations of
      puerarin. Isolated hearts were attached to a Langendorff apparatus and perfused
      with lipopolysaccharide (LPS) and different concentrations of puerarin. The
      hemodynamic parameters of heart rate (HR), left ventricular end systolic pressure
      [LVESP], +dp/dtmax, and -dp/dtmax were recorded. The biochemical indexes of
      lactic dehydrogenase (LDH), tumor necrosis factor alpha (TNF-alpha), and creatine
      kinase (CK) in the coronary effluent were measured at 40, 90, and 120 min of
      perfusion. TNF-alpha in myocardial tissues was measured after perfusion was
      completed. As a result, puerarin (0.24 MUmmol/L-0.48 MUmmol/L) significantly
      increased LVESP, +dp/dtmax, -dp/dtmax, and HR in isolated rat hearts that were
      declined by LPS during perfusion periods. Puerarin could protect against
      increased LDH, CK, and TNF-alpha in coronary effluent of isolated rat hearts by
      LPS during perfusion periods. Treatment of 0.48 MUmmol/L puerarin significantly
      decreased the TNF-alpha in coronary effluent of isolated rat hearts compared with
      the treatment of 0.12 and 0.24 MUmmol/L puerarin, but the TNF-alpha values were
      not reverted to baseline levels. However, the difference of TNF-alpha in
      myocardial tissue in the three puerarin-combined groups was statistically
      significant. This study confirms that puerarin can improve LPS-induced
      contractile dysfunction in isolated heart and inhibit LPS-stimulated myocardial
      TNF-alpha production.

PMID- 29039315
TI  - Prevention of liver cirrhosis by Silymarin.
AB  - This study was designed to evaluate the effects of sylimarin supplementation on
      different biochemical parameters in thioacetamide induced cirrhotic rats. For
      this purpose 24 male Albino wistar rats were divided into four groups (n=6).
      Group I, remained healthy control rats, Group II, received thioacetamide (at a
      dose of 200mg/kg b.w, i.p, for 12 weeks, twice a week) in first phase and saline
      in second phase, Group III, received thioacetamide (200mg/kg b.w, i.p for 12
      weeks, twice a week) in first phase and silymarin (orally at a dosage of 200mg/kg
      b.w, twice a week, for 8 weeks) in second phase and Group IV, received silymarin
      (orally at a dosage of 200mg/kg b.w, twice a week, for 8 weeks) in first phase
      and saline in second phase. Biochemical analysis was evaluated by total and
      direct bilirubin (Retiman and Franhel, 1957, Sherlock, 1951), liver specific
      enzymes, antioxidant enzymes [SOD (Kono et al., 1978), Catalase (Sinha et al.,
      1979), Glutathione reductase (Calberg and Mannervik, 1985) and MDA (Okhawa et
      al., 1979)] and plasma and intraerythrocyte sodium and potassium (Tabssum et al.,
      1996). Marked increase in total and direct bilirubin and ALT activity was the
      indicative markers of liver cirrhosis while reduced antioxidant activity (SOD and
      GSH) and increased MDA and Catalase levels and disturbed electrolyte homeostasis
      were observed in cirrhotic group. Silymarin supplementation markedly reduced
      total bilirubin and ALT activity and restored the antioxidant enzymes (SOD and
      GSH), MDA and catalase activity and electrolyte homeostasis. These results
      indicate that silymarin successively attenuates the thioacetamide induced liver
      cirrhosis.

PMID- 29039316
TI  - In vivo anti-inflammatory and anti-platelet aggregation activities of
      longissiminone A, isolated from Usnea longissima.
AB  - Secondary metabolite, longissiminone A (1) was isolated from a lichen, Usnea
      longissima. It was screened for its' in vivo anti-inflammatroy and anti-platelet
      aggregation activities. Compound 1 showed moderate in vivo anti-inflammatory
      activity as well as moderately active against the aggregation induced by
      arachidonic acid at different doses.

PMID- 29039317
TI  - Progression pattern of rheumatoid arthritis: A study of 500 Pakistani patients.
AB  - To estimate the most prevalent age of patients and disease status and progression
      in terms of severity at different age groups in the Pakistani Rheumatoid
      Arthritis (RA) patients. A total of five hundred (500) RA patients were enrolled
      during October, 2009 to October, 2013. A screening questionnaire was filled for
      each patient satisfying America College of Rheumatology (ACR) criteria under the
      supervision of certified rheumatologists. Epidemiological and demographic
      variables were statistically analyzed for correlation with progression of the
      disease using SPSS ver 17.0.1 software. In general, rheumatoid arthritis
      preferentially affects women with female to male ratio of about 3:1; however,
      patients with above 60 years of age have equal female to male ratio. The most
      prevalent age is 45-60 years. The disease severity increases with increase in the
      age and reaches to its peak in above 60 years of age (p=0.001). The pattern of
      progression of RA in the Pakistani patients is almost consistent with other
      relevant studies conducted on European and European derived populations.

PMID- 29039318
TI  - Enhancing the in vitro release of total flavonoids extract from Dracocephalum
      moldavuca composite phospholipid liposomes optimized by response surface
      methodology.
AB  - The present study was undertaken to optimize the preparation conditions of total
      flavonoids extract from Dracocephalum Moldavuca composite phospholipid liposome
      (TFDMCPL) by response surface methodology (RSM) and to investigate the in vitro
      release (IVR) of TFDMCPL. Method of ethanol injection was adopted to prepare
      TFDMCPL. The single factor experiments were used for the key experimental factors
      and their test range. Based on the single factor experiments, with encapsulation
      efficiency (EE) Size of TFDMCPL and polymey disperse index (PDI) as dependent
      variable, central composite design was adopted to optimize preparation technology
      by taking content of phospholipid and content of cholesterol as independent
      variables, fitting of various mathematical equations were performed using a
      statisitical software of Design-Expert 8.0.6. Preparation parameters were
      optimized through response surface plotted by optimum fitting equations,
      optimized procedure was validated through experimental preparation of TFDMCPL.
      Optimum preparation technology was as following: phospholipid 505mg and
      cholesterol 50mg. Under these condition, encapsulation efficiency was 90.2+/
      1.2%, size of TFDMCPL was 115.6+/-4.3nm, PDI was 0.169+/-0.015 and Zeta potential
      was -15.38+/-0.5. These indicated that TFDMCPL with high entrapping efficiency
      and small particle size could be prepared by the ethanol injection method. And
      TFDMCPL were found to enhance the release of drugs more effectively than TFDM
      based on the in vitro model.

PMID- 29039319
TI  - Heavy metals identification and exposure at workplace environment its extent of
      accumulation in blood of iron and steel recycling foundry workers of Lahore,
      Pakistan.
AB  - The determination of heavy metals in blood is an important occupational
      environmental toxicology screening procedure. The aim of study was to determine
      the concentrations of Pb, Cd, Cr and Ni in blood samples of iron and steel
      foundry workplace exposed workers under routine clinical laboratory conditions.
      The method was employed for the quantitative determination of lead, cadmium,
      chromium and nickel in workplace environment particulate matter blood samples
      from iron and steel foundry workers and in unexposed controls. The results
      indicate that lead, chromium and nickel levels of the exposed workers are
      significantly higher those of the controls. Nickel Concentration (MUg/L) in high
      P value=0.0306 and Chromium Concentration (MUg/L) in P value=0.0295in worker
      population as compared to controls. Lead showed highest Absorption concentration
      in serum from particulate matter to Serum 47.3(MUg/L). Absorption concentration
      of nickel in serum 16.5(MUg/L) was lower than lead observed in worker's
      population. Absorption concentration of cadmium and chromium in serum from
      particulate matter -152(MUg/L) observed very low. The results also show the need
      for immediate improvements in workplace ventilation and industrial hygiene
      practices.

PMID- 29039320
TI  - Pharmacokinetic and bioequivalence studies of fast dispersible ketoprofen tablets
      in healthy volunteers.
AB  - In the present study the pharmacokinetic and bioequivalence parameter of
      Ketoprofen 100 mg fast dispersible tablets (test) were measured with marketed
      (reference) product. This study was accomplished following FDA guidance. A single
      dose, open labeled, cross over (two way), randomized study design was used to
      conduct investigation on 12 Pakistani healthy volunteers. At various time points
      blood samples (10mL) were drawn i.e. at 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12 and
      13hr. Plasma was then separated and ketoprofen concentrations were estimated by
      validated HPLC technique using LC 20A pump (Shimadzu Corp, Japan) and
      Spectrophotometric SPD-20Adetector (Shimadzu Corp, Japan). Ketoprofen
      concentrations were then analyzed by KineticaTM 4.4.1 (Thermo electron corp, USA)
      to estimate various compartmental and noncompartmental pharmacokinetic
      parameters. Various parameters of bioequivalence including AUCtot, AUC0-oo,
      AUClast, Tmaxcalc and Cmaxcalcw ere compared using ANOVA method (two way). For
      log and non-log transformed data the 90% confidence interval values for AUC oo0
      oo, (1.0087-1.0704; 1.0099-1.0714), AUC tot , (0.95482- 1.0093; 0.95486-1.0098),
      AUClast (0.93373-0.98605; 0.93404-0.98603), Cmaxcalc (0.92978-0.9955; 0.92962
      0.99663) and Tmaxcalc (0.89019-0.94116; 0.89095-0.94288) for test and reference
      products respectively. Results were found to be within the FDA satisfactory
      range. For the results verification, Schuirman's one sided t test was used. SPSS
      17.0 (SPSS Inc.) was utilized for the determination of wilcoxon sign rank test.
      Results showed no carry over effect after first study period. Also test product
      met the regulatory criteria for bioequivalence with the reference product. Both
      the formulations were well tolerated.

PMID- 29039321
TI  - Assessment of thyroid hormone levels and thyroid disorders: A case study from
      Gujranwala, Pakistan.
AB  - This case study is conducted to investigate the thyroid hormone levels and
      relevant disorders including evaluation of dietary conditions in the rural area
      of Gujranwala and its surrounding districts. Thyroid disorders are clinically
      prevalent and their manifestation differs considerably with geographical
      variations. A randomized study of 177 subjects was carried out, with a
      questionnaire about their dietary habits/life style and acquisition of blood
      samples for thyroid hormone level assessment using radioimmunoassay technique.
      This study was permitted by the local ethics committee and an informed consent
      was obtained from the patients. Study of normally distributed population with p
      value less than <0.005 and mean age 32.67+/-13 years demonstrated that 37% female
      and 43% males were hyperthyroid with elevated levels of FT3and FT4. Amongst the
      diagnosed cases of hyperthyroidism 47% females and 33% of males were using
      Iodized salt with 50ug/ppm increased concentration of KIO3 in their diet without
      any prescription. Furthermore, 60% of diagnosed hypothyroid cases were having no
      iodine supplementation in their diet. Thyroid function problems are more common
      in females (N=137) than males (N=40) but the severity of this disease was found
      to be more pronounced in males as the TSH level (33.13+/-22.73) was twice that as
      compared to females (17.63+/-18.15). Despite a high prevalence of recognized
      thyroid disease in the population a considerable number of inhabitants have
      undiagnosed thyroid dysfunction. These findings necessities wider scale studies
      for the mapping of thyroid behavior and the contributing factors for this region
      with a population of more than 20 million.

PMID- 29039322
TI  - Antiviral activity of Salidroside from the leaves of Nigerian mistletoe
      (Loranthus micranthus Linn) parasitic on Hevea brasiliensis against respiratory
      syncytial virus.
AB  - Isolated Salidroside from the leaves of Nigerian mistletoe (Loranthus micranthus
      Linn) parasitic on Hevea brasiliensis was evaluated for its antiviral activity
      against respiratory syncytial virus. Semi- preparative HPLC separation of the
      ethyl acetate fraction of the leave extract of Loranthus micranthus Linn
      parasitic on Hevea brasiliensis led to the isolation of a polyphenol. Using
      spectroscopic methods (1D and 2D NMR and mass spectroscopic data) as well as by
      comparison with literature data the structure of the compound was determined as 6
      O-galloyl salidroside. The antiviral activity of the isolated compound was
      evaluated against the respiratory syncytial virus. The isolated Salidroside
      showed potent inhibition towards a recombinant straining respiratory syncytial
      virus with Inhibitory Concentration (IC 50) value of 10.3+/-1.50 MUg/mL. The
      result indicates that Salidroside is an efficient antiviral agent against RSV
      infection and might be useful for the management of RSV pathogenesis.

PMID- 29039323
TI  - Antipyretic effects of hydro-methanol extract of Melia azedarach Linn. seeds and
      Cucumis melo Linn. seeds in experimental rabbits.
AB  - To investigate the antipyretic activity of hydro-methanol extract of Melia
      azedarach Linn. (HMEMA) seeds and Cucumis melo Linn. (HMECM) seeds in
      experimental animals. Baker's yeast was used to induce fever in rabbits which
      were divided into six groups. The animal groups were thereafter administered
      distilled water (control), paracetamol (reference standard, 150mg/kg), HMEMA
      (250mg/kg), HMEMA (500mg/kg), HMECM (250mg/kg) and HMECM (500mg/kg) respectively.
      HMEMA and HMECM were also phytochemically screened for tannins, alkaloids,
      phenols, flavonoids, saponins and cardiac glycosides. Results indicate that hydro
      methanol extract of M. azedarach Linn. Seeds (250mg/kg and 500mg/kg)
      significantly (p<0.001, p<0.05 respectively) reduced the elevated body
      temperature in dose dependant manner. Insignificant to no antipyretic effect was
      produced by hydro-methanol extract of Cucumis melo L. seeds. Phytochemical
      analysis of the HMEMA showed the presence of flavonoids, saponins, tannins,
      phenols, alkaloids and cardiac glycosides While HMECM was positive for
      flavonoids, phenols and saponins. The result shows that there exists a potential
      benefit in utilizing Melia azedarach L. seeds in treating fever. This property
      can be attributed to the presence of phytochemical constituents present in the
      hydro-methanol extract of Melia azedarach L. seeds and the exact mechanism need
      to be evaluated.

PMID- 29039324
TI  - Synthesis, pharmacological screening and computational analysis of some 2-(1H
      Indol-3-yl)-N'-[(un)substituted phenylmethylidene] acetohydrazides and 2-(1H
      Indol-3-yl)-N'-[(un)substituted benzoyl/2-thienylcarbonyl]acetohydrazides.
AB  - The undertaken research was initiated by transforming 2-(1H-Indol-3-yl)acetic
      acid (1) in catalytic amount of sulfuric acid and ethanol to ethyl 2-(1H-Indol-3
      yl)acetate (2), which was then reacted with hydrazine monohydrate in methanol to
      form 2-(1H-Indol-3-yl)acetohydrazide (3). Further, The reaction scheme was
      designed into two pathways where, first pathway involved The reaction of 3 with
      substituted aromatic aldehydes (4a-o) in methanol with few drops of glacial
      acetic acid to generate 2-(1H-Indol-3-yl)-N'
      [(un)substitutedphenylmethylidene]acetohydrazides (5a-o) and in second pathway 3
      was reacted with acyl halides (6a-e) in basic aqueous medium (pH 9-10) to afford
      2-(1H-Indol-3-yl)-N'-[(un)substitutedbenzoyl/2-thienylcarbonyl]acetohydrazides
      (7a-e). All The synthesized derivatives were characterized by IR, EI-MS and 1H
      NMR spectral techniques and evaluated for their anti-bacterial potentials against
      Gram positive and Gram negative bacterial strains and it was found that compounds
      7a-d exhibited antibacterial activities very close to standard Ciprofloxacin. The
      synthesized derivatives demonstrated moderate to weak anti-enzymatic potential
      against alpha-Glucosidase and Butyrylcholinesterase (BChE) where, compounds 7c
      and 5c exhibited comparatively better inhibition against these enzymes
      respectively. Compounds 7a, 7d and 7e showed excellent anti-enzymatic potentials
      against Lipoxygenase (LOX) and their IC50 values were much lower than the
      reference standard Baicalein. Enzyme inhibitory activities were also supported by
      computational docking results. Compounds 5c, 7a, 7b and 7c also showed low values
      of % hemolytic activity as well, showing that these molecules were not toxic,
      indicating that these molecules can be utilized as potential therapeutic agents
      against inflammatory ailments.

PMID- 29039325
TI  - Comparative role of pregabalin and carbamazepine regarding efficacy in painful
      diabetic neuropathy.
AB  - Neuropathic pain is the most severe and resistant type of pain which has impact
      on quality of life and behaviour; it most commonly occurs at night causing
      disturbed sleep. Diabetes mellitus is a common cause of painful neuropathy. In
      this study, we are comparing the effectiveness of old treatment Carbamazepine
      with Pregabalin in painful diabetic neuropathy. The study was an open-label trial
      conducted in Diabetic Clinic of Medical Unit-III, Jinnah Post-graduate Medical
      Center, Karachi. The duration of the study was 90 days, from December 2010 to
      March 2011. The study has been approved from ethical committee of JPMC, Karachi
      with the reference NO.F.2-81/2010-GENL/195/JPMC. 60 established patients of
      painful diabetic peripheral neuropathy from Diabetic Clinic of Medical Unit-III
      OPD were included in the 90-day study, irrespective of gender, with duration of
      diabetes more than 10 years. All subjects are placed into two groups. In group A,
      comprising of 30 patients (n=30), Pregabalin was administered and in group B,
      also comprising of 30 patients (n=30), Carbamazepine. The intensity of pain was
      compared on visual analog scale of McGill pain questionnaire. In group A
      (Pregabalin), the mean pain score fell from 6.17+/-0.14 to 3.50+/-0.15 from day 0
      to day 90 (p-value=0.001) and the percentage of change also in visual analog
      scale of McGill pain questionnaire was -43.31%. In group B (Carbamazepine), the
      changes in pain score from initially 6.07+/-0.14 falling to 4.23+/-0.13 from day
      0 to day 90 (p-value=0.001) and the percentage of change was -30.31%. Pregabalin
      was observed to be more potent. Both drugs were well tolerated by all
      participants that also completed the entire duration of the trial.

PMID- 29039326
TI  - In vitro effects and the related molecular mechanism of galangin and quercetin on
      human gastric cancer cell line (SGC-7901).
AB  - Natural flavonoids are proven to be powerful against various cancers, but few
      studies have investigated the potential effects of two flavonoids galangin and
      quercetin on a human gastric cancer cell line (SGC-7901). In vitro growth
      inhibition and apoptosis of the two flavonoids on the SGC-7901 cells as well as
      potential mechanism about apoptosis induction are reported in the present study.
      The assaying results showed that the two flavonoids at 40-200 MUmmol/L for 24-72
      hours conferred lower cell viability of 14.1-90.3% in dose- and time-dependent
      manner, and at 160 MUmmol/L for 24-48 hours enhanced the proportion of apoptotic
      cells into 13.3-27.4% and 40.6-65.6%, respectively. Galangin was more powerful
      than quercetin to inhibit cell growth, induce apoptosis and decrease
      mitochondrial membrane potential (MMP). Oligonucleotide micro array, real-time RT
      PCR and Western-blot analyses revealed expression changes of the genes and
      proteins in the treated cells, clarifying a mechanism related to apoptosis
      induction. The two flavonoids activated caspase-8, which cleaved Bid into tBid;
      simultaneously, Bax transferred from cytosol into mitochondria to decrease MMP;
      consequentially, cytochrome c released from mitochondria activated caspase-9, and
      then caspase-9 activated caspase-3, which executed the apoptosis. That is, the
      apoptosis occurred via a mitochondrial pathway involving caspase-8/Bid/Bax
      activation.

PMID- 29039327
TI  - Formulation of lyophilized single vial kit of N-N-Ethylene-L-Dicysteine (EC) for
      labeling with 99mTc. II: Radiochemical and clinical evaluation as a renal tubular
      agent in comparison with 99mTc-MAG3.
AB  - A Technetium 99mTc labeled lyophilized single component kit of N-N-ethylene-I
      dicysteine (EC) is developed to replace multiple step kit developed by others.
      The aim of study is to formulate a radionuclide that is easy to prepare, has
      rapid plasma clearance, produce high quality images and is an affective
      alternative to radioiodine labeled orthoiodohippurate, which has been remained
      the physiological 'gold standard' since long time. To achieve this goal, the
      systematically varied key parameters such as pH, the use of reducing agents,
      stabilizers and additives are optimized to obtain maximum radiochemical purity
      and optimum biodistribution in non human and human primates. Various pH levels of
      EC showed equally good results in animal experiments but only pH 10 was suitable
      for human use. Dynamic and renal Scintigraphic studies are carried out with 99mTc
      EC at pH 8 in 12 volunteers and at pH 10 in 18 volunteers and compared with 99mTc
      MAG3, Background ratios, renograms, relative renal function and semi quantitative
      parameters are available in all studies. The background ratios (mean +/- SD) at
      30th minute are 0229+/-0.024 and 0.236+/-0.018 for 99mTc-EC at pH 10 and 99mTc
      MAG3 respectively. The mean +/- standard error of mean (SEM) values of TMAX and
      time to half activity (T12) for 99mTc-EC (pH10) are 3.7+/-0.6 and 7.3+/-1.0
      respectively while for 99mTc-MAG3, they are 4.0+/-0.8 and 7.9+/-1.4 with p values
      0.001 and 0.049 respectively. The values of relative renal function (RRF) for
      99mTc-EC and 99mTc-MAG3 are 50.8+/-3.11 and 51.2+/-3.4 respectively with p value
      of 0.822. The residual activity at 25th minute (A25 / A MAX) and renal uptake are
      0. 209+/-12.67+/-2.80 for 99mTc-EC and 0.218+/-0.035 and 1053+/-2.98 for 99mTc
      MAG3 (p=0.031 an 0.0003) respectively. The correlation coefficient (R2) for TMAX,
      T1/2, A25/AMAX and renal uptake are 0.96, 0.69, 0.93 and 0.85 respectively.

PMID- 29039328
TI  - Synergistic interactions of polyphenols and their effect on antiradical
      potential.
AB  - The aim of the current study was to evaluate interactions among polyphenols from
      different plants and their effect on antioxidant potential. Different mixtures of
      plant extracts of Crataegus oxyacantha (C), Elettaria cardamomum (Cr), Terminalia
      arjuna (T) and Rauvolfia serpentina (R) were prepared and evaluated for total
      phenolics, flavonoid contents, and antioxidant activity. A correlation was also
      established between total phenolics, flavonoids and antioxidant activity.
      Comparative evaluation revealed that phenolics, flavonoids and antioxidant
      activity were found high in plant extracts mixtures than individual plants.
      Highest phenolics (580+/-1.12mg GAE/g), flavonoids (67.10+/-0.11mg CE/g) and
      antioxidant activity (IC50 0.109mg/ml) was observed with ratio 1:1:1:2 of plant
      mixture C, Cr, T, R. A weak linear positive correlation was found between
      antioxidant activity, total phenolic and flavonoid contents. A negative
      correlation was observed among IC50 value, total phenolics and flavonoid
      contents. Investigation through RP-HPLC revealed the presence of different potent
      phenolics in plants understudy. More antioxidant potential of extracts in
      combinations as compared to that of individual plants was clear corroboration of
      synergism. The ratio (1:1:1:2) of the studied plants in combination, that showed
      the highest free radical potential, was another expected better pharmacological
      prospect. This formulation can bring maximum relief against free radical
      associated diseases.

PMID- 29039329
TI  - Synthesis, characterization, antioxidant and brine shrimp cytotoxic activity of
      novel 3-benzothioyl-1-(3-hydroxy-3-phenyl -3-propyl)-1-methylthiourea.
AB  - In the present research work novel ephedrine based thiourea derivative, 3
      benzothioyl-1-(3-hydroxy-3-phenyl -3-propyl)-1-methylthiourea 4is synthesized and
      then characterized elemental analyzed via various techniques i.e., Proton NMR,
      carbon13 NMR and fatherly confirmed via X-ray crystallography. Compound 4 was
      then screened for their possible antioxidant and cytotoxic potentials. Benzoyl
      chloride was treated with an equimolar potassium thiocyanate in acetone to
      achieve benzoyl isothiocyantes. It was then treated with an equimolar (1R, 2S)-(
      )-Ephedrine to obtain the 3-benzothioyl-1-(3-hydroxy-3-phenyl-3-propyl)-1-methyl
      thiourea4. It was then screened for antioxidant and cytotoxic potentials. The
      compound 4 showed excellent antioxidant activity almost comparable to ascorbic
      acid (standard) and have significant cytotoxic activity with LC50 value 05+/-0.58
      ppm.

PMID- 29039330
TI  - Comparison of tranexamic acid pharmacokinetics after intra-articular and
      intravenous administration in rabbits.
AB  - Tranexamic Acid (TXA) is commonly administered in total knee arthroplasty for
      reducing blood loss. There has been a growing interest in the topical use of TXA
      except intravenous use for prevention of bleeding in TKA. The aim of this study
      was to develop and validate a HPLC-MS method to detect TXA and apply to compare
      the pharmacokinetic profile of TXA after intravenous (IV) and topical intra
      articular (IA) application of TXA at a dose of 20 mg/kg in rabbits. In order to
      prove intra-articular administration is better than that of intravenous
      administration from the point of rabbit pharmacokinetic. Two groups of rabbits
      (n=6/group) respectively received TXA intra-articularly or intravenously. Blood
      samples were collected at scheduled time. The concentration of TXA in plasma was
      determined by a validated HPLC-MS method. Excellent linearity was found between
      0.015 and 70.0MUg/ml with a lower limit of quantitation (LLOQ) of 0.015MUg/ml
      (r>0.99); moreover, all the validation data including accuracy and precision
      (intra- and inter-day) were all within the required limits. The pharmacokinetic
      parameters in IA and IV group were: Cmax: 30.65+/-3.31 VS 54.05+/- 6.21MUg/ml
      (p<0.01); t1/2: 1.26+/-0.05 VS 0.68+/-0.13h (p<0.05); AUC0-t: 42.98+/-7.73 VS
      23.39+/-4.14MUg/ml* h (p<0.01), time above the minimum effective concentration
      (%T > MEC): 1.5-2.2 VS 0.7-1.2h (p<0.05). HPLC-MS method is suitable for TXA
      pharmacokinetic studies. The results demonstrated that topical intra-articular
      application of TXA showed a reduced peak plasma concentration and prolonged
      therapeutic drug level compared with intravenous TXA from the point of rabbit
      pharmacokinetic.

PMID- 29039331
TI  - Stabilization studies of sunflower oil with antioxidants extracted from green and
      black cardamom.
AB  - Extracts from green and black cardamom have been used to evaluate their
      antioxidant potential for sunflower oil samples for a period of 45 days.
      Synthetic antioxidants BHA/ BHT were also used parallel over a period of 45 days
      for comparison. Antioxidant potential of natural and synthetic antioxidants were
      evaluated by measuring free fatty acids (FFA), peroxide value (PV) and iodine
      value (IV) values by ambient storage of sunflower oil. The results showed that
      green cardamom extracts were more effective compared to black cardamom extracts.
      However compared to BHA and BHT (200ppm), these were found to be effective at
      higher concentrations.

PMID- 29039332
TI  - Antibacterial activity of different plant extracts and antibiotics on pathogenic
      bacterial isolates from wheat field water.
AB  - The present work was carried out to study bacterial pathogens isolated from wheat
      field water and also effect of some plant extracts on these bacterial pathogens.
      Five bacterial strains were isolated from wheat field water. Different
      morphological and biochemical tests were performed to identify and characterize
      bacterial pathogens. Among isolated strains two belonged to genus Staphylococcus
      sp., other two were Pseudomonas spp. and one strain belonged to genus Salmonella
      sp. Effect of various parameters such as temperature, pH, antibiotics and heavy
      metals of these pathogens were also studied. Optimum temperature for all
      bacterial strains was 37oC and optimum pH was 7 except strain 3 which had pH 6.
      Different antibiotics with different potency were applied to check the resistance
      of bacterial strains against them. Among these antibiotics Cloxacillin and
      Teicoplanin were most potent while Oxacillin was as less potent antibiotic
      because three bacterial strains were resistant against it. While remaining
      antibiotics proved as potent. Seven heavy metals which were zinc (Zn+2), copper
      (Cu+2), Ferrous (Fe+2), mercury (Hg+2), Nickel (Ni+2), chromium (Cr+2) and cobalt
      (Co+2) with different concentrations were applied to bacterial strains. Minimum
      inhibitory concentration of heavy metals for all bacterial was different.
      Different plant extracts (Artemezia incise, Colebrookia oppositifolia, Rhynchosia
      pseudocajan) checked for their antibacterial activity against these pathogens.
      These plant extracts showed antibacterial activity against antibiotic and metal
      resistant bacterial isolates.

PMID- 29039333
TI  - Antioxidant, antibacterial and antiproliferative activities of pumpkin (cucurbit)
      peel and puree extracts - an in vitro study.
AB  - Natural resources right from the beginning of the human civilization has paved
      the way to human being to combat different challenges. The big challenge was to
      safe the human being from diseases and shortage of food. Plants helped the man in
      both areas very efficiently. No doubt when plants are used as food actually we
      are also taking lot of compounds of medicinal values in an excellent combination
      which naturally reduce the risk of diseases. Extraction and purification of
      several medicinally important compounds also gave the way to develop
      pharmaceutical industry in addition to its own therapeutic effects against
      different lethal diseases. Pumpkin is one of the several medicinal important
      vegetables used in different way on the behalf of its admirable power to combat
      different diseases. Antioxidant and biological studies showed very important
      results. A good coherence was found among extraction yield (10.52 to 18.45%),
      total phenolics (1.13 to 6.78 mg GAE/100g), total flavonoids (0.23 to 0.72mg
      CE/100g) and antioxidant potential (?70%). Antibacterial assays of peel and puree
      extracts advocated good potential to stop the growth and division of pathogenic
      bacteria. Further biological activity study was carried out using MDBK cancer
      cell line. The growth inhibitory effect on cancer cell line using MTT assay
      showed methanol extracts of peel and puree both remained efficient to inhibit
      growth (?35%) and cell division of cancer cells. Our results showed that extracts
      of pumpkin puree and its waste, peel, may be utilize to prepare functional food
      against pathogenic born diseases and most active compounds may also be extracted,
      concentrated and converted into tablets or suspension form for therapeutic
      purposes.

PMID- 29039334
TI  - A lignan with glucose uptake activity in 3T3-L1 adipocytes from the stem bark of
      Knema patentinervia.
AB  - A new naturally occurring dibenzylbutyrolactone lignan named isocubebinic ether
      has been isolated from Knema patentinervia. The structure was established by
      spectroscopic methods, which include Ultraviolet, Infrared, Nuclear Magnetic
      Resonance and Mass Spectrometry. The compound showed activity in the stimulation
      of glucose uptake by 3T3-L1 adipocytes.

PMID- 29039335
TI  - Anti-avian influenza virus H9N2 activity of aqueous extracts of Zingiber
      officinalis (Ginger) and Allium sativum (Garlic) in chick embryos.
AB  - In the present study, anti-Avian influenza virus H9N2 activity of aqueous
      extracts (5, 10, 15, 20, 25%) of Zingiber officinalis and Allium sativum was
      evaluated. Embryo-toxicity was evaluated by histopathological scoring of Chorio
      allantoic membrane of chick embryos. Cytotoxicity of extracts was determined by
      MTT assay on Vero cells. Aqueous extract of ginger had antiviral activity at 10,
      15, 20 and 25% while garlic had activity at 15, 20 and 25%. Histopathological
      scoring of chorio-allantoic membrane for aqueous extracts (5, 10, 15, 20, 25%) of
      ginger (0.66+/-0.57, 1.33+/-0.57, 1.66+/-0.57, 2.66+/-0.57, 3.66+/-0.57,
      respectively) and garlic (1.00+/-0.00, 1.33+/-0.57, 2.00+/-0.00, 2.33+/-0.57,
      3.66+/-0.57, respectively) was concentration dependant. MTT assay revealed
      cytotoxicity of both plants was also concentration dependent. Extracts of ginger
      (5, 10, 15, 20, 25%) had lower cytotoxicity (71, 59, 28, 22, 0 % cell survival,
      respectively) as compared to garlic (61, 36. 20, 11, 3% cell survival,
      respectively). Overall results revealed that concentration of aqueous extract of
      ginger (10%), showing antiviral activity against H9N2, was less toxic to vero
      cells (> 50% cell survival). It is insinuated that ginger may have anti- Avian
      influenza virus H9N2 potential and its active compounds needs further
      investigations.

PMID- 29039336
TI  - Soil transmitted helminthiasis in different occupational groups in Swat, Khyber
      Pakhtunkhwa, Pakistan.
AB  - We investigated the prevalence of geohelminth parasites in farmers, education
      concerned and shepherd of Swat, Khyber Pakhtunkhwa, Pakistan. A total of 1041
      stool samples were examined from January 2006 to December 2008 using direct smear
      (Normal saline and Lugol's Iodine solution) the concentration methods and
      procedures. Seven hundred and sixty three (73.2%) individuals were found infected
      with one or more than one geohelminth parasites. Four hundred and eighteen
      (54.7%) were infected with single parasite and three hundred forty five (45.3%)
      with multiple infections. Ascaris lumbricoides 460 (53.0%), Trichuris trichura
      228 (26.2%), Enterobius vermicularis 123 (14.1%) and Ancylostoma duedenale 56
      (6.45%) were detected. The adults were found more parasitized than children and
      males were more infected than females. Shepherds were found more infected than
      farmers and education concerned. Although Swat is an area with poor hygiene
      located in temperate zone near the border of Afghanistan and China. The
      prevalence of reported geohelminth parasites here compared with the same studies
      is unexpectedly high. These types of studies should continue time to time to know
      the hazardous of such parasitic infections for the betterment of the human
      health.

PMID- 29039337
TI  - Synthesis, acute toxicity, analgesic activity and cytotoxicity of Some
      bisthiourea derivatives.
AB  - Bisthiourea derivatives were synthesized by the reaction of benzoylisothiocyanate
      and diamines to give 1,2-Bis(N'-benzoylthioureidobenzene (1), 1,3
      di(benzoylthioureido)benzene (2) and 1,4-di(benzoylthioureido)benzene (3) in
      acetone. Acute toxicity study revealed that LD50 of compound (1) and (3) is 120
      mg/kg body weight. Visceral pain induced by injecting i.p acetic acid in mice
      were strongly inhibited by all the compounds. 94.65, 95.25 and 85.54% analgesic
      activity were observed in compounds (1), (2) and (3) at 15 mg/kg and (2) and (3)
      shows 97.63 and 96.42% at 30 mg/kg body weight respectively while (1) gives 100%
      analgesic activity. 100% cytotoxicity was observed in compounds (2) and (3) and
      96% in compound (1) at 750 ppm. The results suggest that these compounds may have
      potential values for treatment of cancer and painful disorders.

PMID- 29039338
TI  - Anti-Inflammatory and antiviral effects of water-soluble crude extract from
      Phragmites australis in vitro.
AB  - Phragmitesaustralis (P. australis), a worldwide distributed wetland grass, is
      traditionally used as food-making helper and spice in China. The pharmacological
      effect of this plant is poorly understood. Here, we demonstrated that
      lipopolysaccharide (LPS)-induced production of inflammatory mediators nitric
      oxide (NO) and reactive oxygen species (ROS), and the pro-inflammatory cytokines
      tumor necrosis factor-a (TNF-a) and interleukin-1beta (IL-1beta) in RAW264.7
      macrophage were significantly inhibited by the crude extract. The inflammation
      pertinent signaling extra cellular signal-regulated kinase 1/2 (Erk1/2), P38MAPK,
      C-Jun and NF-kappaB (NF-kappaB) activated by LPS could be dramatically inhibited
      by this extract. It also remarkably inhibited bovine herpes virus type 1 (BoHV-1)
      replication in MDBK cells. Taken together, here, for the first time we provided
      P. australisa a novel natural herb as a potential candidate for the generation of
      antiviral and anti-inflammatory agent.

PMID- 29039339
TI  - Effects of two functionally important SLCO1B1 gene polymorphisms on
      pharmacokinetics of atorvastatin.
AB  - Organic anion transporter polypeptide 1B1 (OATP1B1) encoded by (SLCO1B1) gene, an
      uptake transporter involved in the transport of drugs and endogenous compounds
      and located in hepatocyte sinusoidal membrane. Objective of study was to
      investigate the effects of two functionally significant SNPs (388A>G and 521T>C)
      and their respective genotypes of SLCO1B1 gene encoding OATP1B1 on the
      pharmacokinetics of atorvastatin. A total of 100 subjects divided into 6 groups
      as per their genotype profile were recruited. A single dose of 80mg atorvastatin
      was orally administered and plasma concentration measured up to 48 hours. The
      388A>G and 521T>C genotypes were significantly associated with each other when
      compared for AUC and Cmax but exhibited no significant variations in Tmax and
      t1/2. 521 SNP is rather more strongly associated with altered pharmacokinetics of
      atorvastatin when compared with the 388 SNP, though the homozygous bi-allelic
      variant of 388 SNP also exhibited a fairly significant variation along with
      homozygous bi-allelic variant of 521 SNP. The inter-individual variation in
      pharmacokinetics can be explained by SLCO1B1 polymorphism.

PMID- 29039340
TI  - In vitro antibacterial and antifungal activities of different solvent extracted
      samples from the stem of Euphorbia heliscopia.
AB  - This paper presents the anti-microbial potentials of methanol, ethyl acetate, n
      hexane, butanol and water extracted samples from the stem of Euphorbia heliscopia
      against S. aureus (Gram positive), B. subtilis (Gram positive), P. aeruginosa
      (Gram negative), K. pneumonia (Gram negative), E. coli (Gram negative), C.
      albicans (fungal specie) by discs diffusion susceptibility assay using 0.5 and
      1mg disc-1 concentrations. Our results showed that all the extracted samples from
      the stem of E. heliscopia exhibited varying degree of antimicrobial activity.
      Ethyl acetate extracted samples measured maximum activity against the studies
      microbial species followed by the n-butanol and crude methanolic extract. n
      hexane extracted samples inhibited the growth of all microbial species except P.
      aeruginosa and E. coli at lower concentration. Aqueous fractions showed
      inhibitory activity against B. subtilis, K. pneumonia and C. albicans. The most
      susceptible gram positive bacteria were S. aureus while B. subtilis was the most
      resistant one. Among Gram negative bacteria, P. aeruginosa showed more
      susceptibility while K. pneumonia was resistant.

PMID- 29039341
TI  - The practice of self-medication among Pakistani university students.
AB  - Self-medication refers to the selection and use of medicines without prescription
      by an individuals' personal responsibility as a cure of self-identified disease.
      Although its rationale, type and extent may different from culture to culture, it
      is globally prevalent practice. In Pakistan no research is available on the use
      of self-medication among university students. The existing study was conducted to
      investigate the frequency and percentages of branded medicines used by university
      students, reasons and rationale behind self-medication. It was a survey research
      design and descriptive statistics were collected regarding the use of self-
      medication. Hence, a sample of 300 students was employed between the age range of
      16-25 years (M = 20.23, SD = 2. 76). The respondents filled a questionnaire
      regarding socio-economic and demographic variables, use of self-medication, and
      medication knowledge. Information was obtained on the conditions treated with
      medication, the medications used, and attitude towards self-medication. Results
      indicated mostly used type of self-medication was allopathic (f = 230, 77%).
      Headache was found to be more frequently prevalent disease. Most frequently used
      medicine was Disprin (M = 49.68, SD = 15. 14) as a cure of headaches and other
      body pains. Financial problems (f = 90, 30%) left over drugs (f = 46, 15%) and
      easy accessibility (f =38, 12.7%) were found to be the strongest factors in using
      self-medication. Moreover significant differences appeared in the use of type of
      medicines between boys and girls. The study concluded that self-medication is
      widely used practice among university students in Pakistan.

PMID- 29039342
TI  - Report - In vitro immune potentials of a water-soluble polysaccharide extract
      from Dioscorea opposita planted in Henan Province, China.
AB  - Dioscorea opposita is an edible and medicinal plant available in many areas of
      China. This study aimed to assess in vitro immune potentials of a water-soluble
      polysaccharide extract from D. opposita planted in Henan Province, China. In
      vitro effects of the extract on three immune cells (macrophages, natural killer
      cells and splenocytes) from mice and secretion of eight immune-related molecules
      in macrophages and splenocytes were evaluated. In total, the extract exhibited a
      dose-dependent manner on these immunological responses. The extract at dose level
      of 50MUg/ml enhanced respective splenocyte proliferation, macrophage
      phagocytosis, and natural killer cell activity by 150%, 18% and 47%, increased
      secretion of interleukin-2 and interferon-gamma (from 41.4 and 24.6 pg/ml to 48.8
      and 91.5 pg/ml, respectively) but decreased secretion of interleukin-4 (from 38.9
      to 27.9 pg/ml) in splenocytes. The extract at the same dose level also stimulated
      inducible nitric oxide synthase and lysozyme in macrophages, and enhanced
      secretion of interleukin-6, interleukin-1beta and tumor necrosis factor-alpha
      (from 26.6, 73.4 and 39.6 pg/ml to 60.2, 131.0 and 144.7 pg/ml, respectively). It
      is concluded that water-soluble polysaccharides from D. opposita have immune
      potentials to the body, via activating immune cells and regulating the secretion
      of immune-related molecules.

PMID- 29039343
TI  - Mini Review - Phenolics for skin photo-aging.
AB  - Photo-aging is one of the foremost problems caused by generation of reactive
      oxygen species when skin is exposed on UV irradiation. In view of that,
      generation of reactive oxygen species intermingle with proteins, DNA, saccharides
      and fatty acids triggering oxidative mutilation and effects are in the appearance
      of distressed cell metabolism, morphological and ultra-structural changes,
      mistreat on the routes and revisions in the demarcation, propagation and skin
      apoptosis living cells which leads to photo-aging. Plant phenolics are
      universally found in both edible and inedible plants and have extended
      substantial interest as photo-protective for human skin due to their antioxidant
      activities. The objective of this review is to highlight the use of plant
      phenolics for their antioxidant activities against photo-aging.

PMID- 29039344
TI  - Mini Review - Analysis of Artemether and Dihydroartemisinin by high performance
      high liquid chromatography in biological fluids-issues and solutions.
AB  - Artemether-Lumefantrine is the most widely recommended antimalarial combination
      used to treat millions of patients suffering from malaria. Artemether undergoes
      rapid metabolism and gets converted to its active metabolite dihydroartemisisn.
      Drug analysis is a vital aspect to evaluate drugs in research. There are a number
      of methods available for the determination of artemether in biological fluids.
      These methods include HPLC based UV detection, GS-MS, HPLC-ECD and HPLC-MS/MS.
      This article reviews different methods for the determination of artemether in the
      biological fluids. Among the available methods HPLC-MS/MS proves to be the most
      accurate and reliable one for analysis. This has the advantage of improved
      sensitivity and selectivity with smaller sample volume.

PMID- 29039345
TI  - Validation of Transition Readiness Assessment Questionaire in Turkish Adolescents
      with Diabetes.
AB  - BACKGROUND: Today, more than 90% of adolescents with chronic conditions survive
      into adulthood and move from pediatric care to adult care for the management of
      their chronic illness. It is important to grant autonomy and ensure that
      adolescents/young adults are ready to use the adult health care system prior to
      the transfer of care. However, the lack of a transition readiness assessment tool
      that is validated, patient-centered, and appropriate to developmental differences
      in pediatric care is a major obstacle for the transition of care from pediatric
      services to adult services. AIMS: This study examined the validity and
      reliability of the Turkish version of the Transition Readiness Assessment
      Questionnaire, which assesses the readiness for transition from pediatric to
      adult health care for adolescents/young adults with diabetes mellitus. STUDY
      DESIGN: Methodological study. METHODS: Participants were 109 adolescents/young
      adults with type 1 diabetes mellitus aged 14-21 years. After permission was
      obtained to adapt the Transition Readiness Assessment Questionnaire, the Turkish
      Transition Readiness Assessment Questionnaire and self-care scale were
      administered to participants through face-to-face interviews at two pediatric
      endocrinology clinics. Validity was evaluated by exploratory and confirmatory
      factor analysis and content-scope validity assessment; reliability was evaluated
      by item-total score correlation and continuity methods. Internal reliability was
      assessed by Cronbach's alpha coefficient and criterion validity assessment.
      RESULTS: The item analysis, exploratory factor analysis, and confirmatory factor
      analysis identified five basic dimensions, with high internal consistency (0.89
      0.75). The ratio chi2/df and other conformity indices were a good fit to the
      data. The correlation coefficient in the analyses of test-retest scores was 0.86
      for the total scale (p<0.05), and the Cronbach's alpha coefficient was 0.88 for
      overall scale. CONCLUSION: The Turkish Transition Readiness Assessment
      Questionnaire is a valid and reliable measure of the transition readiness of
      adolescents/young adults with diabetes mellitus in Turkey. The Transition
      Readiness Assessment Questionnaire assesses the self-management abilities and
      health care transition knowledge of adolescents/young adults with diabetes
      mellitus who need special health care. It can also serve as a guide for health
      care professionals in detecting the educational fields that are necessary for
      acquiring self-management and self-care abilities.

PMID- 29039346
TI  - Astrogliosis has Different Dynamics after Cell Transplantation and Mechanical
      Impact in the Rodent Model of Parkinson's Disease.
AB  - BACKGROUND: Transplantation of fetal mesencephalic tissue is a well-established
      concept for functional reinnervation of the dopamine-depleted rat striatum.
      However, there is no extensive description of the glial response of the host
      brain following this procedure. AIMS: The present study aimed to quantitatively
      and qualitatively analyse astrogliosis surrounding intrastriatal grafts and
      compare it to the reaction to mechanical injury with the transplantation
      instrument only. STUDY DESIGN: Animal experimentation. METHODS: The standard 6
      hydroxydopamine-induced unilateral model of Parkinson's disease was used. The
      experimental animals received transplantation of a single-cell suspension of E14
      ventral mesencephalic tissue. Control animals (sham-transplanted) were subjected
      to injury by the transplantation cannula, without injection of a cell suspension.
      Histological analyses were carried out 7 and 28 days following the procedure by
      immunohistochemistry assays for tyrosine hydroxylase and glial fibrillary acidic
      protein. To evaluate astrogliosis, the cell density and immunopositive area were
      measured in distinct zones within and surrounding the grafts or the cannula
      tract. RESULTS: Statistical analysis revealed that astrogliosis in the grafted
      striatum increased from day 7 to day 28, as shown by a significant change in both
      cell density and the immunopositive area. The cell density increased from 816.7+/
      370.6 to 1403+/-272.1 cells/mm2 (p<0.0001) and from 523+/-245.9 to 1164+/-304.8
      cells/mm2 (p<0.0001) in the two zones in the graft core, and from 1151+/-218.6 to
      1485+/-210.6 cells/mm2 (p<0.05) for the zone in the striatum immediately adjacent
      to the graft. The glial fibrillary acidic protein-expressing area increased from
      0.3109+/-0.1843 to 0.7949+/-0.1910 (p<0.0001) and from 0.1449+/-0.1240 to 0.702+/
      0.2558 (p<0.0001) for the same zones in the graft core, and from 0.5277+/-0.1502
      to 0.6969+/-0.1223 (p<0.0001) for the same area adjacent to the graft zone.
      However, astrogliosis caused by mechanical impact only (control) did not display
      such dynamics. This finding suggests an influence of the grafted cells on the
      host's glia, possibly through cross-talk between astrocytes and transplanted
      neurons. CONCLUSION: This bidirectional relationship is affected by multiple
      factors beyond the mechanical trauma. Elucidation of these factors might help
      achieve better functional outcomes after intracerebral transplantation.

PMID- 29039347
TI  - Ferritin as a potential biomarker of efficacy of treatment of atrial fibrillation
      - preliminary report.
AB  - BACKGROUND: Complex mechanisms of responsible for originating and maintaining of
      atrial fibrillation (AF) are involved in pathophysiology of this arrhythmia.
      Inflammation substantially contribute to arrhythmic remodelling of atrial
      tissue.The aim of the present study is to assess an applicability of ferritin and
      high sensitive C-reactive protein (hs-CRP) as biomarkers of atrial fibrillation
      and their usefulness in evaluation of efficacy of cryoablation. MATERIALS AND
      METHODS: The study population consisted of 40 patients who underwent first AF
      cryoablation procedure. The whole follow-up time was for 6 months. The efficacy
      of cryoablation was defined as lack of episodes of AF longer than 30 s reported
      either in patient's medical documentation or present in standard or Holter ECG
      records. Concentrations of hs-CRP (latex method ) and ferritin (immunochemical
      method) were determined in standard way in hospital laboratory. RESULTS: The
      recurrence of atrial fibrillation during follow-up was detected in 7 of 40
      patients (efficacy 82.5%). Basal concentrations of hs-CRP and ferritin were
      significantly higher in patients who underwent ablation during AF. Ablation
      resulted in an increase of either hs-CRP or ferritin concentrations. After seven
      days, both hs-CRP and ferritin concentrations returned to basal level. The trend
      toward the higher concentration of hs-CRP was observed in AF recurrence subgroup
      in 30th and the 90th day after the procedure. Ferritin concentrations were
      significantly higher in recurrence subgroup after 30 and 90 days. CONCLUSION: Our
      results suggest that the evaluation of ferritin serum level can be a potential
      tool for assessment of AF treatment efficacy.

PMID- 29039348
TI  - The impact of agonists and antagonists of TLR3 and TLR9 on concentrations of IL
      6, IL10 and sIL-2R in culture supernatants of peripheral blood mononuclear cells
      derived from patients with systemic lupus erythematosus.
AB  - Toll-like receptors (TLR), especially TLR3, 7 and 9, play an important role in
      the pathogenesis of systemic lupus erythematosus (SLE). In our study blood was
      collected from 16 patients with SLE and from 8 healthy volunteers. Concentrations
      of IL-6, IL-10 and sIL-2R were measured by ELISA in mononuclear cell culture
      supernatant after 24 hours of stimulation by agonists and antagonists of TLR3 and
      9 (for TLR3-poli I/C, resveratrol and for TLR9-ODN2006, IRS 945). Stimulation of
      TLR9 by ODN2006 led to an increase of IL-6 concentration in cell culture
      supernatants from the cells of healthy volunteers compared with unstimulated
      cells from controls. Inhibition of TLR3 activation by resveratrol caused a
      significantly lower concentration of IL-10 in cell culture supernatants derived
      from both patients and healthy donors. Moreover, resveratrol significantly
      decreased the level of IL-10 and sIL-2R in culture supernatants of cells derived
      from patients with active disease compared to the inactive stage. A positive
      correlation was also found between IL-6 concentration following ODN2006
      administration and disease activity. In conclusions, our results indicate that
      TLRs play a role in the modulation of the inflammatory response in SLE patients.
      This suppressive action on IL-10 synthesis demonstrated by resveratrol suggests
      that it may be useful in SLE therapy.

PMID- 29039349
TI  - Non-nutritional use of breast milk.
AB  - Mammals milk, in addition to nutrients, contains many biologically active
      substances including immunoglobulins, growth factors, cytokines, acute phase
      proteins, and antimicrobial and antiviral proteins. Thanks to its unique
      composition, for hundreds of years it is used in post-natal care, treatment of
      wounds, as well as to fight bacterial and viral infections. The discovery of stem
      cells and HAMLET complex in breast milk resulted in increased interest in human
      breast milk as a natural medicine. Milk therapy is devoid of side effects, and
      breast milk banks may serve as a potential source of milk as a drug substance. In
      this study we collected information about the possible non-nutritional use of
      breast milk.

PMID- 29039350
TI  - The toxicity of vanadium on gastrointestinal, urinary and reproductive system,
      and its influence on fertility and fetuses malformations.
AB  - Vanadium is a transition metal that has a unique and beneficial effect on both
      humans and animals. For many years, studies have suggested that vanadium is an
      essential trace element. Its biological properties are of interest due to its
      therapeutic potential, including in the treatment of diabetes mellitus. Vanadium
      deficiencies can lead to a range of pathologies. However, excessive concentration
      of this metal can cause irreversible damage to various tissues and organs.
      Vanadium toxicity mainly manifests in gastrointestinal symptoms, including
      diarrhea, vomiting, and weight reduction. Vanadium also exhibits hepatotoxic and
      nephrotoxic properties, including glomerulonephritis and pyelonephritis. Vanadium
      compounds may also lead to partial degeneration of the seminiferous epithelium of
      the seminiferous tubules in the testes and can affect male fertility. This paper
      describes the harmful effects of vanadium on the morphology and physiology of
      both animal and human tissues, including the digestive system, the urinary tract,
      and the reproductive system. What is more, the following study includes data
      concerning the correlation between the above-mentioned metal and its influence on
      fertility and fetus malformations. Additionally, this research identifies the
      doses of vanadium which lead to pathological alterations becoming visible within
      tissues. Moreover, this study includes information about the protective efficacy
      of some substances in view of the toxicity of vanadium.

PMID- 29039352
TI  - Atomic layer deposited oxide films as protective interface layers for integrated
      graphene transfer.
AB  - The transfer of chemical vapour deposited graphene from its parent growth
      catalyst has become a bottleneck for many of its emerging applications. The
      sacrificial polymer layers that are typically deposited onto graphene for
      mechanical support during transfer are challenging to remove completely and hence
      leave graphene and subsequent device interfaces contaminated. Here, we report on
      the use of atomic layer deposited (ALD) oxide films as protective interface and
      support layers during graphene transfer. The method avoids any direct contact of
      the graphene with polymers and through the use of thicker ALD layers (>=100 nm),
      polymers can be eliminated from the transfer-process altogether. The ALD film can
      be kept as a functional device layer, facilitating integrated device
      manufacturing. We demonstrate back-gated field effect devices based on single
      layer graphene transferred with a protective Al2O3 film onto SiO2 that show
      significantly reduced charge trap and residual carrier densities. We critically
      discuss the advantages and challenges of processing graphene/ALD bilayer
      structures.

PMID- 29039351
TI  - Epidemiology, risk factors and prognosis of Interferon alpha induced thyroid
      disorders. A Prospective Clinical Study.
AB  - INTRODUCTION: Hepatitis C virus (HCV) infection is a worldwide problem and
      hepatitis, which is its natural unfavourable course, is still a challenge for
      hepatologist. At present, standards of treatment are changing from combined
      therapy with interferon alpha (IFN-alpha) and ribavirin to new antiviral drugs.
      The current classification divides interferon induced thyroid diseases (IITD)
      into two groups: autoimmune (Hashimoto disease, Graves disease, positive
      antithyroid autoantibodies in euthyroid patients) and non-autoimmune (destructive
      thyroiditis, non-autoimmune hypothyroidism). A common complication of cytokine
      therapy is the induction of antithyroid autoantibodies de novo without thyroid
      dysfunction. During therapeutic regimens combined with ribavirin, destructive
      thyroiditis with typical biphasic course is more common than in IFN-alpha
      monotherapy. Clinically, overt pathologies often have discrete symptoms, which
      cause diagnostic and therapeutic dilemmas. AIMS: The aim of this study was to
      estimate IITD occurrence, to find risk factors for IITD development. MATERIAL AND
      METHODS: The study group consisted of 66 patients treated for HCV infection.
      Before and during antiviral therapy, hormonal (TSH, fT4, fT3), immunological
      (thyroid autoantibodies), ultrasonographic and genetic (HLA-A2) parameters were
      evaluated. RESULTS: Hormonal disturbances were detected in 24.2% of patients;
      however, 43.9% of patients had positive thyroid autoantibodies (de novo) without
      hormonal imbalance. Multivariate analysis revealed the following: female sex,
      elevated TSH level, occurrence of anti-TPO autoantibodies (TPO-Ab), and increased
      blood velocity in thyroid arteries are risk factors for IITD development. IN
      CONCLUSION: Thyroid disorders are common during IFN-alpha therapy. Previous
      epidemiological data seem to be underestimated. Important risk factors for IITD
      development are: female sex, elevated serum TSH concentration (>=2.5 MUU/mL),
      positive TPO-Ab and increased blood velocity in thyroid arteries.

PMID- 29039353
TI  - A high-performance mesoporous carbon supported nitrogen-doped carbon
      electrocatalyst for oxygen reduction reaction.
AB  - Investigating low-cost and highly active electrocatalysts for oxygen reduction
      reactions (ORR) is of crucial importance for energy conversion and storage
      devices. Herein, we design and prepare mesoporous carbon supported nitrogen-doped
      carbon by pyrolysis of polyaniline coated on CMK-3. This electrocatalyst exhibits
      excellent performance towards ORR in alkaline media. The optimized nitrogen-doped
      mesoporous electrocatalyst show an onset potential (E onset) of 0.95 V (versus
      reversible hydrogen electrode (RHE)) and half-wave potential (E 1/2) of 0.83 V
      (versus RHE) in 0.1 M KOH. Furthermore, the as-prepared catalyst presents
      superior durability and methanol tolerance compared to commercial Pt/C indicating
      its potential applications in fuel cells and metal-air batteries.

PMID- 29039354
TI  - Gas-sensing enhancement methods for hydrothermal synthesized SnO2-based sensors.
AB  - Gas sensing for hydrothermal synthesized SnO2-based gas sensors can be enhanced
      in three ways: structural improvement, composition optimization, and processing
      improvement. There have been zero-dimensional, one-dimensional, and three
      dimensional structures reported in the literature. Controllable synthesis of
      different structures has been deployed to increase specific surface area. Change
      of composition would intensively tailor the SnO2 structure, which affected the
      gas-sensing performance. Furthermore, doping and compounding methods have been
      adopted to promote gas-sensing performance by adjusting surface conditions of
      SnO2 crystals and constructing heterojunctions. As for processing area, it is
      very important to find the optimal reaction time and temperature. In this paper,
      a gas-solid reaction rate constant was proposed to evaluate gas-sensing
      properties and find an excellent hydrothermal synthesized SnO2-based gas sensor.

PMID- 29039355
TI  - Highly stable cesium lead iodide perovskite quantum dot light-emitting diodes.
AB  - Recently, all-inorganic perovskites such as CsPbBr3 and CsPbI3, have emerged as
      promising materials for light-emitting applications. While encouraging
      performance has been demonstrated, the stability issue of the red-emitting CsPbI3
      is still a major concern due to its small tolerance factor. Here we report a
      highly stable CsPbI3 quantum dot (QD) light-emitting diode (LED) with red
      emission fabricated using an improved purification approach. The device achieved
      decent external quantum efficiency (EQE) of 0.21% at a bias of 6 V and
      outstanding operational stability, with a L 70 lifetime (EL intensity decreases
      to 70% of starting value) of 16 h and 1.5 h under a constant driving voltage of 5
      V and 6 V (maximum EQE operation) respectively. Furthermore, the device can work
      under a higher voltage of 7 V (maximum luminance operation) and retain 50% of its
      initial EL intensity after 500 s. These findings demonstrate the promise of
      CsPbI3 QDs for stable red LEDs, and suggest the feasibility for electrically
      pumped perovskite lasers with further device optimizations.

PMID- 29039356
TI  - Strain-modulation-assisted enhanced broadband photodetector based on large-area,
      flexible, few-layered Gr/MoS2 on cellulose paper.
AB  - Electronic structure and carrier behavior in semiconductor junctions can be
      effectively modulated on the application of strain. This work represents the
      first demonstration of a large-area, flexible, paper-based graphene-molybdenum
      disulfide (Gr/MoS2) broadband photodetector using a low-cost solution-processed
      hydrothermal method and enhancement in photodetection through strain modulation
      by assembling the device on polydimethylsiloxane. Optimization, in terms of
      process parameters, was carried out to obtain trilayer MoS2 over Gr-cellulose
      paper. Under strain, potential barrier variation and piezopotential induced in
      MoS2 leads to 79.41% enhancement in photodetection in the visible region.
      Piezopotential induced in MoS2 lowers the conduction-band energy thereby
      increasing the effective electric field favoring easy electron-hole separation.
      The advantage of vertically stacked Gr/MoS2 for the photodetector is the
      utilization of the entire area as a junction where effective separation of
      electron-hole pairs occurs. Detailed studies of the mechanism in terms of
      potential barrier variation in Gr/MoS2 and an energy-band diagram are presented
      to help understand the proposed phenomenon. The present work demonstrates the
      significance of few-layer MoS2 or Gr in relation to strain-modulated photosensing
      in comparison to their counterparts grown via chemical vapor deposition. The
      results provide an excellent approach for the fabrication of low-cost
      heterojunctions for improved optoelectronic performance, which can be further
      extended to similar 2D-material heterojunctions for analog, digital and
      optoelectronic applications.

PMID- 29039357
TI  - Synergetic effect of Sn addition and oxygen-deficient atmosphere to fabricate
      active hematite photoelectrodes for light-induced water splitting.
AB  - This work describes the design of a microwave-assisted method using hydrothermal
      conditions to fabricate pure and Sn-doped hematite photoelectrodes with varied
      synthesis time and additional thermal treatment under air and N2 atmosphere. The
      hematite photoelectrode formed under N2 atmosphere, with Sn deposited on its
      surface-which is represented by material synthesized at 4 h -exhibits the highest
      performance. Hence, Sn addition followed by high temperature annealing conducted
      in an oxygen-deficient atmosphere seems to create oxygen vacancies, and to
      prevent the segregation of dopant to form the SnO2 phase at the hematite crystal
      surface, reducing its energy and suppressing the grain growth. The increased
      donor number density provided by the oxygen vacancies (confirmed by x-ray
      photoelectron data), and a possible reduction in the grain boundary energy or
      hematite crystal interface might favor charge separation, and increase the
      electron transfer through the hematite into the back contact (FTO substrate). In
      consequence, the light-induced water oxidation reaction efficiency of Sn-hematite
      photoelectrodes was significantly increased in comparison with pure ones, even
      though the vertical rod morphology was not preserved. This finding provides a
      novel insight into intentional Sn addition, revealing that dopant segregation at
      the hematite crystal surface (or at the grain boundaries) could-by increasing the
      electron mobility-be the more relevant factor in developing active hematite
      photoelectrodes than the control of columnar morphology.

PMID- 29039358
TI  - Hydrothermal synthesis of SnQ (Q = Te, Se, S) and their thermoelectric
      properties.
AB  - Lead-free IV-VI semiconductors SnQ (Q = Te, Se, S) are deemed as promising
      thermoelectric (TE) materials. In this work, we designed a hydrothermal route to
      selectively synthesize single phase SnTe, SnSe and SnS nanopowders. For all three
      samples, the phase structure were characterized by x-ray diffraction, SnTe
      particles with octahedron structure and SnSe/SnS particles with plate-like shape
      were observed by field emission scanning electron microscopy and transmission
      electron microscopy, the formation mechanism was discussed in detail. Then, SnTe,
      SnSe and SnS nanopowders were densified by spark plasma sintering for
      investigating TE properties. It was noticed that SnSe and SnS exhibited
      remarkably anisotropy in both electrical and thermal properties attributed to the
      layered crystal structure. The highest ZT values 0.79 at 873 K, 0.21 at 773 K,
      and 0.13 at 773 K were achieved for SnTe, SnSe and SnS bulk samples,
      respectively.

PMID- 29039359
TI  - Piezotronic effect tuned AlGaN/GaN high electron mobility transistor.
AB  - The piezotronic effect utilizes strain-induced piezoelectric polarization charges
      to tune the carrier transportation across the interface/junction. We fabricated a
      high-performance AlGaN/GaN high electron mobility transistor (HEMT), and the
      transport property was proven to be enhanced by applying an external stress for
      the first time. The enhanced source-drain current was also observed at any gate
      voltage and the maximum enhancement of the saturation current was up to 21% with
      15 N applied stress (0.18 GPa at center) at -1 V gate voltage. The physical
      mechanism of HEMT with/without external compressive stress conditions was
      carefully illustrated and further confirmed by a self-consistent solution of the
      Schrodinger-Poisson equations. This study proves the cause-and-effect
      relationship between the piezoelectric polarization effect and 2D electron gas
      formation, which provides a tunable solution to enhance the device performance.
      The strain tuned HEMT has potential applications in human-machine interface and
      the security control of the power system.

PMID- 29039360
TI  - Visualization and automatic detection of defect distribution in GaN atomic
      structure from sampling Moire phase.
AB  - Quantitative detection of defects in atomic structures is of great significance
      to evaluating product quality and exploring quality improvement process. In this
      study, a Fourier transform filtered sampling Moire technique was proposed to
      visualize and detect defects in atomic arrays in a large field of view. Defect
      distributions, defect numbers and defect densities could be visually and
      quantitatively determined from a single atomic structure image at low cost. The
      effectiveness of the proposed technique was verified from numerical simulations.
      As an application, the dislocation distributions in a GaN/AlGaN atomic structure
      in two directions were magnified and displayed in Moire phase maps, and defect
      locations and densities were detected automatically. The proposed technique is
      able to provide valuable references to material scientists and engineers by
      checking the effect of various treatments for defect reduction.

PMID- 29039361
TI  - Characterization of highly crystalline lead iodide nanosheets prepared by room
      temperature solution processing.
AB  - Two-dimensional (2D) semiconducting materials are particularly appealing for many
      applications. Although theory predicts a large number of 2D materials,
      experimentally only a few of these materials have been identified and
      characterized comprehensively in the ultrathin limit. Lead iodide, which belongs
      to the transition metal halides family and has a direct bandgap in the visible
      spectrum, has been known for a long time and has been well characterized in its
      bulk form. Nevertheless, studies of this material in the nanometer thickness
      regime are rather scarce. In this article we demonstrate an easy way to
      synthesize ultrathin, highly crystalline flakes of PbI2 by precipitation from a
      solution in water. We thoroughly characterize the produced thin flakes with
      different techniques ranging from optical and Raman spectroscopy to temperature
      dependent photoluminescence and electron microscopy. We compare the results to ab
      initio calculations of the band structure of the material. Finally, we fabricate
      photodetectors based on PbI2 and study their optoelectronic properties.

PMID- 29039362
TI  - The influence of atmosphere on the performance of pure-phase WZ and ZB InAs
      nanowire transistors.
AB  - We compare the characteristics of phase-pure MOCVD grown ZB and WZ InAs nanowire
      transistors in several atmospheres: air, dry pure N2 and O2, and N2 bubbled
      through liquid H2O and alcohols to identify whether phase-related
      structural/surface differences affect their response. Both WZ and ZB give poor
      gate characteristics in dry state. Adsorption of polar species reduces off
      current by 2-3 orders of magnitude, increases on-off ratio and significantly
      reduces sub-threshold slope. The key difference is the greater sensitivity of WZ
      to low adsorbate level. We attribute this to facet structure and its influence on
      the separation between conduction electrons and surface adsorption sites. We
      highlight the important role adsorbed species play in nanowire device
      characterisation. WZ is commonly thought superior to ZB in InAs nanowire
      transistors. We show this is an artefact of the moderate humidity found in
      ambient laboratory conditions: WZ and ZB perform equally poorly in the dry gas
      limit yet equally well in the wet gas limit. We also highlight the vital role
      density-lowering disorder has in improving gate characteristics, be it stacking
      faults in mixed-phase WZ or surface adsorbates in pure-phase nanowires.

PMID- 29039363
TI  - Ab initio phonon thermal transport in monolayer InSe, GaSe, GaS, and alloys.
AB  - We compare vibrational properties and phonon thermal conductivities (kappa) of
      monolayer InSe, GaSe, and GaS systems using density functional theory and Peierls
      Boltzmann transport methods. In going from InSe to GaSe to GaS, system mass
      decreases giving both increasing acoustic phonon velocities and decreasing
      scattering of these heat-carrying modes with optic phonons, ultimately giving
      [Formula: see text]. This behavior is demonstrated by correlating the scattering
      phase space limited by fundamental conservation conditions with mode scattering
      rates and phonon dispersions for each material. We also show that, unlike flat
      monolayer systems such as graphene, in InSe, GaSe and GaS thermal transport is
      governed by in-plane vibrations. Alloying of InSe, GaSe, and GaS systems provides
      an effective method for modulating their kappa through intrinsic vibrational
      modifications and phonon scattering from mass disorder giving reductions ~2-3.5
      times. This disorder also suppresses phonon mean free paths in the alloy systems
      compared to those in their crystalline counterparts. This work provides
      fundamental insights of lattice thermal transport from basic vibrational
      properties for an interesting set of two-dimensional materials.

PMID- 29039364
TI  - Investigation of the in-plane and out-of-plane electrical properties of metallic
      nanoparticles in dielectric matrix thin films elaborated by atomic layer
      deposition.
AB  - Pt nanoparticles in a Al2O3 dielectric matrix thin films are elaborated by means
      of atomic layer deposition. These nanostructured thin films are integrated in
      vertical and planar test structures in order to assess both their in-plane and
      out-of-plane electrical properties. A shadow edge evaporation process is used to
      develop planar devices with electrode separation distances in the range of 30 nm.
      Both vertical and planar test structures show a Poole-Frenkel conduction
      mechanism. Low trap energy levels (<0.1 eV) are identified for the two test
      structures which indicates that the Pt islands themselves are not acting as traps
      in the PF mechanism. Furthermore, a more than three order of magnitude current
      density difference is observed between the two geometries. This electrical
      anisotropy is attributed to a large electron mobility difference in the in-plane
      and out-of-plane directions which can be related to different trap distributions
      in both directions.

PMID- 29039366
TI  - A Socio-Technical Analysis of Patient Accessible Electronic Health Records.
AB  - In Sweden, and internationally, there is a movement towards increased
      transparency in healthcare including giving patients online access to their
      electronic health records (EHR). The purpose of this paper is to analyze the
      Swedish patient accessible EHR (PAEHR) service using a socio-technical framework,
      to increase the understanding of factors that influence the design,
      implementation, adoption and use of the service. Using the Sitting and Singh
      socio-technical framework as a basis for analyzing the Swedish PAEHR system and
      its context indicated that there are many stakeholders engaged in these types of
      services, with different driving forces and incentives that may influence the
      adoption and usefulness of PAEHR services. The analysis was useful in
      highlighting important areas that need to be further explored in evaluations of
      PAEHR services, and can act as a guide when planning evaluations of any PAEHR
      service.

PMID- 29039367
TI  - Availability of Computerised Medical Record System Data to Compare Models of
      Child Health Care in Primary Care Across Europe.
AB  - Computerised medical record (CMR) system data can be used to compare different
      models of health care for children. We identified sources of data from the Models
      of Child Health Appraised (MOCHA) project that compares family doctor led with
      paediatrician led and mixed models of child care using index conditions. Asthma
      and immunisation coverage are the first of these. We explored the extent to which
      an established Patient Registries Initiative (PARENT); MOCHA's own survey
      (MIROI); the European Centre for Disease Control (ECDC) immunisation information
      system survey and the European Network of Centres for Pharmacoepidemiology and
      Pharmacovigilance (ENCePP) registry of data sources provided data to make
      comparisons of child health care. Five countries had data repositories for our
      index conditions from paediatrician lead services, compared with 14 for mixed,
      and 11 for family doctor led services. PARENT identified 212 sources, MIROI 148
      sources, ECDC 17 sources and ENCePP 42; with immunisation related data sources
      found in all four but asthma in only three. There are less sources of electronic
      data available to study paediatrician led systems than other models; this risks
      unequal sample size bias.

PMID- 29039368
TI  - Connecting Parents to a Pediatric Emergency Department: Designing a Mobile App
      Based on Patient Centred Care Principles.
AB  - INTRODUCTION: Patient centred care fosters a holistic approach of care switching
      the focus from a disease perspective to a patient's experience perspective.
      Patient centred care is of particular importance in the context of paediatric
      emergency medicine. Indeed, parents entering a paediatric emergency department
      (PED) are usually under stress caused by their children's illness, the unfamiliar
      setting of the PED and delays of care. All these factors can deteriorate their
      experience as well as the relationships between healthcare providers, the
      patients and their parents. METHODS: We explore potential areas to improve the
      patient experience during his journey into PED. The dimensions of the picker's
      patient centred care are used to guide observations, conduct interviews and focus
      groups. The areas of improvement are then operationalized through their
      translation into app functionalities. RESULTS: Our novel application allows
      supporting users on 7 of the 8 dimensions of picker's patient centred care model.
      The app supports parents in their decision-making to consult a PED, it provides
      relevant medical information to avoid unrealistic expectations and accompany the
      family after discharge thanks to tailored information sheets about diagnostics.
      CONCLUSION: Our mobile app allows to make a big step toward the improvement of
      the patient-caregiver relationship. The direct benefits will be shared by
      patients and caregivers, as well as the institution.

PMID- 29039369
TI  - Identification and Description of Healthcare Customer Communication Patterns
      Among Individuals with Diabetes in Clalit Health Services: A Retrospective
      Database Study.
AB  - HMOs record medical data and their interactions with patients. Using this data we
      strive to identify sub-populations of healthcare customers based on their
      communication patterns and characterize these sub-populations by their socio
      demographic, medical, treatment effectiveness, and treatment adherence profiles.
      This work will be used to develop tools and interventions aimed at improving
      patient care. The process included: (1) Extracting socio-demographic, clinical,
      laboratory, and communication data of 309,460 patients with diabetes in 2015,
      aged 32+ years, having 7+ years of the disease treated by Clalit Healthcare
      Services; (2) Reducing dimensions of continuous variables; (3) Finding the K
      communication-patterns clusters; (4) Building a hierarchical clustering and its
      associated heatmap to summarize the discovered clusters; (5) Analyzing the
      clusters found; (6) Validating results epidemiologically. Such a process supports
      understanding different communication-channel usage and the implementation of
      personalized services focusing on patients' needs and preferences.

PMID- 29039370
TI  - De-Identification of Medical Narrative Data.
AB  - Maintaining data security and privacy in an era of cybersecurity is a challenge.
      The enormous and rapidly growing amount of health-related data available today
      raises numerous questions about data collection, storage, analysis, comparability
      and interoperability but also about data protection. The US Health Portability
      and Accountability Act (HIPAA) of 1996 provides a legal framework and a guidance
      for using and disclosing health data. Practically, the approach proposed by HIPAA
      is the de-identification of medical documents by removing certain Protected
      Health Information (PHI). In this work, a rule-based method for the de
      identification of French free-text medical data using Natural Language Processing
      (NLP) tools will be presented.

PMID- 29039371
TI  - Regional Monitoring of Cervical Cancer.
AB  - Cervical cancer is one of the most important causes of death in women in fertile
      age in Romania. In order to discover high-risk situations in the first stages of
      the disease it is important to enhance prevention actions, and ICT, respectively
      cloud computing and Big Data currently support such activities. The national
      screening program uses an information system that based on data from different
      medical units gives feedback related to the women healthcare status and provides
      statistics and reports. In order to ensure the continuity of care it is updated
      with HL7 CDA support and cloud computing. The current paper presents the solution
      and several results.

PMID- 29039372
TI  - Weighting Experience-Based Decision Support on the Basis of Clinical Outcomes'
      Assessment.
AB  - Technologies such as decision support systems are expected to help clinicians
      implement clinical practice guidelines (CPGs) with the aim of decreasing practice
      variations and improving clinical outcomes. However, if CPGs provide
      recommendations to improve patient care, they may fail to take into account
      actual clinical outcomes associated to the recommended treatment, such as adverse
      events or secondary effects. In this paper, we present a novel experience-based
      decision support approach applied to the management of breast cancer, the most
      commonly diagnosed cancer among women worldwide. Capitalizing on the clinical
      know-how of physicians and the modeling of patient's outcomes and toxicities in a
      computer interpretable way, we are able to discover new knowledge that helps
      improving patient-centered clinical care. This work is conducted within the EU
      Horizon 2020 project DESIREE.

PMID- 29039373
TI  - DisEpi: Compact Visualization as a Tool for Applied Epidemiological Research.
AB  - Outcomes research and evidence-based medical practice is being positively
      impacted by proliferation of healthcare databases. Modern epidemiologic studies
      require complex data comprehension. A new tool, DisEpi, facilitates visual
      exploration of epidemiological data supporting Public Health Knowledge Discovery.
      It provides domain-experts a compact visualization of information at the
      population level. In this study, DisEpi is applied to Attention
      Deficit/Hyperactivity Disorder (ADHD) patients within Clalit Health Services,
      analyzing the socio-demographic and ADHD filled prescription data between 2006
      and 2016 of 1,605,800 children aged 6 to 17 years. DisEpi's goals facilitate the
      identification of (1) Links between attributes and/or events, (2) Changes in
      these relationships over time, and (3) Clusters of population attributes for
      similar trends. DisEpi combines hierarchical clustering graphics and a heatmap
      where color shades reflect disease time-trends. In the ADHD context, DisEpi
      allowed the domain-expert to visually analyze a snapshot summary of data mining
      results. Accordingly, the domain-expert was able to efficiently identify that:
      (1) Relatively younger children and particularly youngest children in class are
      treated more often, (2) Medication incidence increased between 2006 and 2011 but
      then stabilized, and (3) Progression rates of medication incidence is different
      for each of the 3 main discovered clusters (aka: profiles) of treated children.
      DisEpi delivered results similar to those previously published which used
      classical statistical approaches. DisEpi requires minimal preparation and fewer
      iterations, generating results in a user-friendly format for the domain-expert.
      DisEpi will be wrapped as a package containing the end-to-end discovery process.
      Optionally, it may provide automated annotation using calendar events (such as
      policy changes or media interests), which can improve discovery efficiency,
      interpretation, and policy implementation.

PMID- 29039375
TI  - DataWell: Public Involvement in the Development of a Federated Platform for
      Shared Patient Records in Greater Manchester, U.K.
AB  - Sharing personal health data for direct care, health improvement, planning and
      research is recognised as important to improving the quality and safety of care.
      However, the complexities of sharing data, including technology, information
      governance and consent issues, means that many projects have difficulty
      communicating with the public about why they wish to share data, or what the
      benefits might be. Great Manchester Academic Health Science Network has
      established a Public Experience Group to help co-design the requirements for a
      health information exchange, called DataWell, across over 30 health and care
      organisations in Greater Manchester. This group has allowed the programme to
      uniquely respond to questions of how consent and data sharing should work with
      DataWell for direct care, as well as exploring other uses of the data, including
      planning and research.

PMID- 29039374
TI  - The Meaning of Patient Empowerment in the Digital Age: The Role of Online Patient
      Communities.
AB  - Traditionally, patient empowerment has been used as a strategy for health
      promotion. The rise of online communities of patients represents a good example
      of how patient empowerment occurs, independently of the intervention of existing
      healthcare providers and insurers, allowing thus a more accurate definition of
      meaning of this concept. We describe two situations related with the development
      of health-related social networks: (1) The emergence of a new biomedical research
      model in which patients lead research, shifting the equilibrium of power from the
      professionals to research subjects themselves, and (2) The emergence of Lay Crowd
      Sourced Expertise in these communities, arising from the daily exchange among
      patients affected by chronic conditions and their relatives, giving place to a
      new era of bottom-up data generation, previously unknown in biomedical sciences.
      We enrich these descriptions by analyzing interviews to key actors of these "on
      line" communities": Michael Chekroun, founder of "Carenity, France", and Paul
      Wicks Vice President at "PatientsLikeMe, USA".

PMID- 29039376
TI  - Decision Support Systems in Health Care - Velocity of Apriori Algorithm.
AB  - The amount of stored data in health information systems can reach tera- and
      petabytes and application of specific algorithms in the field of data mining
      makes finding useful information suitable for making quality business decisions.
      A frequently used method for determining the rules of the relationship between
      attributes is the Association rule by applying Apriori algorithm. Lack of basic
      Apriori algorithm is derived from the slow work due to multiple scanned data
      sets. By examining the speed of generating the basic rules in relation to the
      improved Apriori algorithm by using software RapidMiner confirmed that the time
      required to generate rules for Improved algorithm is shorter, the rules are
      quickly generated particularly for large data sets, which is an advantage for
      making decisions.

PMID- 29039377
TI  - A Case Study of the Technology Use and Information Flow at a Hospital-Driven
      Telemedicine Service.
AB  - Health care services face the challenge of providing individualised treatment to
      a growing ageing population prone to chronic conditions and multi-morbidities.
      The research project Patients and Professionals in Productive Teams aims to study
      health care services that are run with a patient-centred teamwork approach. In
      this context, a case study was made of a hospital-driven telemedicine service for
      chronic obstructive pulmonary disease patients after hospital discharge, with a
      focus on information flow and technology use. The methods used were observation
      and interviews with key informants. The results showed that the technology was
      perceived as well-functioning for telemedicine support, but the technology used
      was a standalone system and not integrated with the electronic health record of
      the hospital. In addition, there was lack of support to provide the patients at
      home with written instructions on advices of medical treatment and care. The
      electronic information used for this telemedicine services, allowed shared access
      of information for teamwork between professional only within the hospital.

PMID- 29039378
TI  - DNA Encoding Training Using 3D Gesture Interaction.
AB  - The work described in this paper summarizes the development process and presents
      the results of a human genetics training application, studying the 20 amino acids
      formed by the combination of the 3 nucleotides of DNA targeting mainly medical
      and bioinformatics students. Currently, the domain applications using recognized
      human gestures of the Leap Motion sensor are used in molecules controlling and
      learning from Mendeleev table or in visualizing the animated reactions of
      specific molecules with water. The novelty in the current application consists in
      using the Leap Motion sensor creating new gestures for the application control
      and creating a tag based algorithm corresponding to each amino acid, depending on
      the position in the 3D virtual space of the 4 nucleotides of DNA and their type.
      The team proposes a 3D application based on Unity editor and on Leap Motion
      sensor where the user has the liberty of forming different combinations of the 20
      amino acids. The results confirm that this new type of study of
      medicine/biochemistry using the Leap Motion sensor for handling amino acids is
      suitable for students. The application is original and interactive and the users
      can create their own amino acid structures in a 3D-like environment which they
      could not do otherwise using traditional pen-and-paper.

PMID- 29039381
TI  - Taking Nursing Informatics into the Future.
AB  - The new board EFMIs Working Group have has planned the future strategy for
      involving nurses in informatics. The strategy is to bring nursing informatics
      into the future. It is important to ensure that the next generation of nurses is
      involved in the work with Nursing Informatics and share knowledge. It must be
      done with a targeted effort including of social media and a more offensive effort
      at the annual MIE meetings.

PMID- 29039396
TI  - Identifying Personal Goals of Patients With Long Term Condition: A Service Design
      Thinking Approach.
AB  - Care for patients with long term conditions is often characterized as fragmented
      and ineffective, and fails to engage the resources of patients and their families
      in the care process. Information and communication technology can potentially
      help bridge the gap between patients' lives and resources and services provided
      by professionals. However, there is little attention on how to identify and
      incorporate the patients' individual needs, values, preferences and care goals
      into the digitally driven care settings. We conducted a case study with
      healthcare professionals and patients participated applying a service design
      thinking approach. The participants could elaborate some personal goals of
      patients with long term condition which can potentially be incorporated in
      digitally driven care plans using examples from their own experiences.

PMID- 29039407
TI  - Smart Information Management in Health Big Data.
AB  - The smart information management system (SIMS) is concerned with the organization
      of anonymous patient records in a big data and their extraction in order to
      provide needful real-time intelligence. The purpose of the present study is to
      highlight the design and the implementation of the smart information management
      system. We emphasis, in one hand, the organization of a big data in flat file in
      simulation of nosql database, and in the other hand, the extraction of
      information based on lookup table and cache mechanism. The SIMS in the health big
      data aims the identification of new therapies and approaches to delivering care.

PMID- 29039413
TI  - VTA mTOR Signaling Regulates Dopamine Dynamics, Cocaine-Induced Synaptic
      Alterations, and Reward.
AB  - Mechanistic target of rapamycin (mTOR) regulates long-term synaptic plasticity,
      learning, and memory by controlling dendritic protein synthesis. The mTOR
      inhibitor rapamycin has been shown to attenuate the behavioral effects of drugs
      of abuse, including cocaine. Using viral vectors to selectively delete mTOR in
      the ventral tegmental area (VTA) in adult male mTORloxP/loxP mice, we
      investigated the role of mTOR in regulating neuronal morphology, basal synaptic
      transmission, dopamine dynamics, and cocaine-induced synaptic plasticity and
      rewarding effects. We find that targeted deletion of mTOR in the VTA had no
      significant effects on soma size and dendritic morphology of VTA neurons but
      significantly decreased dopamine release and reuptake in the nucleus accumbens
      (NAc) shell, a major target region. Western blot analysis revealed that mTOR
      deletion led to decreases in phosphorylated tyrosine hydroxylase (pTH-Ser40)
      levels in the VTA and dopamine transporter expression in the NAc. mTOR deletion
      had no significant effects on basal excitatory transmission in VTA dopamine
      neurons but caused an increase in GABAergic inhibition because of an increase in
      VTA GABAergic neuron firing. Furthermore, mTOR deletion attenuated conditioned
      place preference to cocaine and cocaine-induced potentiation of excitation and
      reduction of GABAergic inhibition in VTA dopamine neurons. Taken together, these
      results suggest that loss of mTOR in the VTA shifts the balance of excitatory and
      inhibitory synaptic transmission and decreases dopamine release and reuptake in
      the NAc. In addition, VTA mTOR signaling regulates cocaine-cue associative
      learning and cocaine-induced synaptic plasticity in VTA dopamine neurons.

PMID- 29039412
TI  - Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via
      VEGF-mediated alternative activation of macrophage.
AB  - Intermittent fasting (IF), a periodic energy restriction, has been shown to
      provide health benefits equivalent to prolonged fasting or caloric restriction.
      However, our understanding of the underlying mechanisms of IF-mediated metabolic
      benefits is limited. Here we show that isocaloric IF improves metabolic
      homeostasis against diet-induced obesity and metabolic dysfunction primarily
      through adipose thermogenesis in mice. IF-induced metabolic benefits require
      fasting-mediated increases of vascular endothelial growth factor (VEGF)
      expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF
      overexpression could recapitulate the metabolic improvement of IF in non-fasted
      animals. Importantly, fasting and adipose-VEGF induce alternative activation of
      adipose macrophage, which is critical for thermogenesis. Human adipose gene
      analysis further revealed a positive correlation of adipose VEGF-M2 macrophage
      WAT browning axis. The present study uncovers the molecular mechanism of IF
      mediated metabolic benefit and suggests that isocaloric IF can be a preventive
      and therapeutic approach against obesity and metabolic disorders.

PMID- 29039414
TI  - The Limbic System in Youth Depression: Brain Structural and Functional
      Alterations in Adolescent In-patients with Severe Depression.
AB  - Adolescent-onset major depressive disorder (MDD) is associated with an increased
      risk of recurrent depressive episodes, suicidal behaviors, and psychiatric
      morbidity throughout the lifespan. The objective of the present study was to
      investigate brain structural and functional changes in adolescent patients with
      MDD. Furthermore, we aimed to clarify the influence of early-life stress on brain
      function and structure. The study investigated adolescent patients with severe
      MDD (n=20, mean age=16.0, range=15-18 years) and a control sample of matched
      healthy adolescents (n=21, mean age=16.6, range=15-18 years). Functional MRI data
      were obtained using a face-matching paradigm to investigate emotion processing.
      Structural MRI data were analyzed using voxel-based morphometry (VBM). In line
      with previous studies on adult MDD, adolescent patients showed elevated amygdala
      activity to negative and reduced amygdala activity to positive emotional stimuli.
      Furthermore, MDD patients showed smaller hippocampal volumes compared to healthy
      adolescents. Higher levels of childhood maltreatment were associated with smaller
      hippocampal volumes in both depressed patients and healthy controls, whereby no
      associations between amygdala reactivity and childhood maltreatment were found.
      Our results suggest that hippocampal alterations in youth MDD patients may at
      least partly be traced back to higher occurrence of early-life adverse
      experiences. Regarding the strong morphometric impact of childhood maltreatment
      and its distinctly elevated prevalence in MDD populations, this study provides an
      alternative explanation for frequently observed limbic structural abnormalities
      in depressed patients.

PMID- 29039415
TI  - CRISPR-UMI: single-cell lineage tracing of pooled CRISPR-Cas9 screens.
AB  - Pooled CRISPR screens are a powerful tool for assessments of gene function.
      However, conventional analysis is based exclusively on the relative abundance of
      integrated single guide RNAs (sgRNAs) between populations, which does not discern
      distinct phenotypes and editing outcomes generated by identical sgRNAs. Here we
      present CRISPR-UMI, a single-cell lineage-tracing methodology for pooled
      screening to account for cell heterogeneity. We generated complex sgRNA libraries
      with unique molecular identifiers (UMIs) that allowed for screening of clonally
      expanded, individually tagged cells. A proof-of-principle CRISPR-UMI negative
      selection screen provided increased sensitivity and robustness compared with
      conventional analysis by accounting for underlying cellular and editing-outcome
      heterogeneity and detection of outlier clones. Furthermore, a CRISPR-UMI positive
      selection screen uncovered new roadblocks in reprogramming mouse embryonic
      fibroblasts as pluripotent stem cells, distinguishing reprogramming frequency and
      speed (i.e., effect size and probability). CRISPR-UMI boosts the predictive
      power, sensitivity, and information content of pooled CRISPR screens.

PMID- 29039416
TI  - Antibodies to biotin enable large-scale detection of biotinylation sites on
      proteins.
AB  - Although purification of biotinylated molecules is highly efficient, identifying
      specific sites of biotinylation remains challenging. We show that anti-biotin
      antibodies enable unprecedented enrichment of biotinylated peptides from complex
      peptide mixtures. Live-cell proximity labeling using APEX peroxidase followed by
      anti-biotin enrichment and mass spectrometry yielded over 1,600 biotinylation
      sites on hundreds of proteins, an increase of more than 30-fold in the number of
      biotinylation sites identified compared to streptavidin-based enrichment of
      proteins.

PMID- 29039417
TI  - Protein interaction perturbation profiling at amino-acid resolution.
AB  - The identification of genomic variants in healthy and diseased individuals
      continues to rapidly outpace our ability to functionally annotate these variants.
      Techniques that both systematically assay the functional consequences of
      nucleotide-resolution variation and can scale to hundreds of genes are urgently
      required. We designed a sensitive yeast two-hybrid-based 'off switch' for
      positive selection of interaction-disruptive variants from complex genetic
      libraries. Combined with massively parallel programmed mutagenesis and a
      sequencing readout, this method enables systematic profiling of protein
      interaction determinants at amino-acid resolution. We defined >1,000 interaction
      disrupting amino acid mutations across eight subunits of the BBSome, the major
      human cilia protein complex associated with the pleiotropic genetic disorder
      Bardet-Biedl syndrome. These high-resolution interaction-perturbation profiles
      provide a framework for interpreting patient-derived mutations across the entire
      protein complex and thus highlight how the impact of disease variation on
      interactome networks can be systematically assessed.

PMID- 29039419
TI  - Prostate cancer: The importance of the mitochondrial genome.

PMID- 29039418
TI  - Rapid nonlinear image scanning microscopy.
AB  - Image scanning microscopy (ISM) doubles the resolution of a conventional confocal
      microscope for super-resolution imaging. Here, we describe an all-optical ISM
      design based on rescanning microscopy for two-photon-excited fluorescence and
      second-harmonic generation that allows straightforward implementation into
      existing microscopes. The design offers improved sensitivity and high frame rates
      relative to those of existing systems. We demonstrate its utility using fixed and
      living specimens as well as collagen hydrogels.

PMID- 29039420
TI  - Kidney cancer: PSMA: a potential therapeutic target in RCC.

PMID- 29039421
TI  - Haematological cancer: Extended EFS with rituximab.

PMID- 29039423
TI  - Breast Cancer: Abemaciclib effective in combination with aromatase inhibition.

PMID- 29039424
TI  - Skin cancer: Propranolol limits melanoma recurrence.

PMID- 29039422
TI  - Drug development for noncastrate prostate cancer in a changed therapeutic
      landscape.
AB  - The unprecedented progress in the treatment of metastatic castration-resistant
      prostate cancer is only beginning to be realized in patients with noncastrate
      disease. This slow progress in part reflects the use of trial objectives focused
      on time-to-event end points, such as time to metastasis and overall survival,
      which require long follow-up durations and large sample sizes, and has been
      further delayed by the use of approved therapies that are effective at the time
      of progression. Our central hypotheses are that progress can be accelerated, and
      that outcomes can be improved by shifting trial objectives to response measures
      occurring early that solely reflect the effects of the treatment. To test these
      hypotheses, a continuously enrolling multi-arm, multi-stage randomized trial
      design, analogous to that used in the STAMPEDE trial, has been developed.
      Eligibility is focused on patients with incurable disease or those with a high
      risk of death with any form of monotherapy alone. The primary objective is to
      eliminate all disease using a multimodality treatment strategy. End points
      include pathological complete response and an undetectable level of serum
      prostate-specific antigen, with recovery of serum testosterone levels. Both are
      binary, objective, and provide an early, quantitative indication of efficacy.

PMID- 29039425
TI  - Imaging biomarkers exist and they underpin clinical decision-making.
AB  - This corrects the article DOI: 10.1038/nrclinonc.2017.84.

PMID- 29039426
TI  - Corrigenda: Premna bhamoensis (Lamiaceae, Premnoideae), a new species from Kachin
      State, northeastern Myanmar.
AB  - [This corrects the article DOI: 10.3897/phytokeys.83.12869.].

PMID- 29039427
TI  - Towards a taxonomy of topology for polynuclear aromatic hydrocarbons: linking
      electronic and molecular structure.
AB  - Trends linking the topological characteristics of polynuclear aromatic
      hydrocarbons (PAH) to their electronic properties are reported. TD-DFT electronic
      spectra computations, using the 6-31G* basis set and B3LYP exchange correlation
      functional, were calculated for a series of PAH, allowing for the HOMO-LUMO gaps
      to be reported. Clar structures provide an avenue to link the physical structure
      and the aromaticity of the molecule; which, when extended by bond length and
      harmonic oscillator model of aromaticity analysis, provide powerful tools to
      understand the link between electronic and physical structure. These results lead
      to the conclusion that all PAH structures show a decrease in HOMO-LUMO gap as a
      function of size, but the rate of that decrease is directly related to the
      topology of the molecules. A PAH taxonomy was developed that categorizes PAH into
      categories with similar topological properties, which allows for modelling of
      changes in the HOMO-LUMO gap with PAH size. An atom-pair minimization algorithm
      was used to calculate the binding energy (BE) of homogeneous dimers of the
      studied PAH. The BE per carbon atom increases with the overall size of the
      structure to an asymptotic limit, but as with the HOMO-LUMO gap, topology plays a
      critical secondary factor. Previously published, experimentally determined
      optical band gaps (OBG) from Tauc/Davis-Mott analysis of extinction spectra in
      various laminar, non-premixed flames produced a correlation between the HOMO-LUMO
      gaps of high-symmetry, nearly circular D2h symmetry molecules to molecular size.
      The work presented here provides a much more nuanced and predictive evaluation of
      how OBG depends on structure and size.

PMID- 29039428
TI  - Photolysis of polymeric self-assembly controlled by donor-acceptor interaction.
AB  - A photodegradable supramolecular polymer was constructed using cucurbit[8]uril
      (CB[8]) and an alkoxyanthracene guest. The monomeric unit was photostable because
      of the intramolecular donor-acceptor interaction. However, upon complexation with
      CB[8], the photolysis of alkoxyanthracene was enhanced, which endowed the
      supramolecular polymer with great photoreactivity.

PMID- 29039429
TI  - Highly active 3-dimensional cobalt oxide nanostructures on the flexible carbon
      substrates for enzymeless glucose sensing.
AB  - The demand for electrochemical sensors with high sensitivity and reliability,
      fast response, and excellent selectivity has stimulated intensive research on
      developing highly active nanomaterials. In this work, freestanding 3D/Co3O4 thorn
      like and wire-like (nanowires) nanostructures are directly grown on a flexible
      carbon fiber paper (CFP) substrate by a single-step hydrothermal process without
      using surfactants or templates. The 3D/Co3O4 thorn-like nanostructures show
      higher electrochemical activity than wire-like because of their high
      conductivity, large specific surface areas, and mesopores on their surface. The
      characterization of 3D/Co3O4 nanostructures is performed by using high resolution
      transmission electron microscopy (HRTEM), field emission scanning electron
      microscopy (FESEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction
      analysis (XRD), and electrochemical methods. The 3D/Co3O4 thorn-like
      nanostructures displayed non-enzymatic higher catalytic activity towards the
      electrochemical detection of glucose, compared to the 3D/Co3O4 wire-like
      morphology. The 3D/Co3O4 thorn-like nanostructures show a wide linear range
      response of glucose concentration ranging from 1 to 1000 MUM with a detection
      limit of 0.046 MUM (S/N = 3). The 3D/Co3O4 thorn-like nanostructure-modified CFP
      electrode selectively detects glucose in the presence of 100-fold excess of
      interfering compounds. The 3D/Co3O4 thorn-like nanostructure-modified CFP
      electrode is tested with human blood serum samples and validated with commercial
      glucose sensors. The newly developed sensor material shows potential for glucose
      monitoring in clinical and food samples.

PMID- 29039430
TI  - Hybrid heterojunctions between a 2D transition metal dichalcogenide and metal
      phthalocyanines: their energy levels vis-a-vis current rectification.
AB  - We form junctions between a monolayer of a range of metal-phthalocyanines and a
      monolayer of 2D transition metal dichalcogenides (TMD) through an electrostatic
      adsorption process. The energy levels of the components, as drawn from scanning
      tunneling spectroscopy (STS) and the density of states (DOS) thereof, indicated
      that the hybrid junctions would act as current rectifiers. We have observed that
      the central metal atom affected the energies of the metalorganics and thereby the
      rectification ratio of the junctions. In addition, since planar single molecule
      magnets (SMMs) were used in which magnetization appears due to the 3d-electrons
      of the metal, we could align the molecules followed by their structural
      immobilization. We have observed that such an alignment changed their molecular
      orbitals and hence affected the energy levels at the interface. The rectification
      ratio of molecule|TMD hybrid junctions depends on the metal in metalorganics and
      also on their alignment with the substrate electrode. In effect, the
      rectification ratio in a range of junctions has been correlated to the energy
      level diagram at the interface.

PMID- 29039431
TI  - Correction: Sisters together: co-sensitization of near-infrared emission of
      ytterbium(iii) by BODIPY and porphyrin dyes.
AB  - Correction for 'Sisters together: co-sensitization of near-infrared emission of
      ytterbium(iii) by BODIPY and porphyrin dyes' by Hongshan He et al., Chem.
      Commun., 2017, 53, 10120-10123.

PMID- 29039432
TI  - Substitution pattern on anthrol carbaldehydes: excited state intramolecular
      proton transfer (ESIPT) with a lack of phototautomer fluorescence.
AB  - Photophysical properties and excited state intramolecular proton transfer (ESIPT)
      reactivity for anthrol carbaldehydes 1-5 have been investigated computationally
      and experimentally by steady-state and time-resolved fluorescence and laser flash
      photolysis (LFP). 1,2-Disubstituted anthrol carbaldehydes 1 and 2 are not ESIPT
      reactive, contrary to naphthol analogues. The main deactivation channels from S1
      for 1 and 2 are fluorescence (PhiF = 0.1-0.2) and intersystem crossing (ISC) to
      almost isoenergetic T2 states. The triplet states from 1 and 2 were detected by
      LFP (in N2-purged CH3CN, tau = 15 +/- 2 MUs for 1, and tau = 5.5 +/- 0.1 MUs for
      2). In contrast, 2,3-disubstituted anthrols 3-5 undergo efficient barrierless
      ultrafast ESIPT. However, the typical dual emission from locally excited states
      and ESIPT tautomers were not observed since ESIPT proceeds via a conical
      intersection with S0 delivering the keto-tautomer in the hot ground state.
      Therefore, anthrols 3-5 are about ten times less fluorescent compared to 1 and 2,
      and the emission for 3-5 originates from less-populated conformers that cannot
      undergo ESIPT. Keto-tautomers for 3-5 were detected in CH3CN by LFP (lambdamax =
      370 nm, tau = 30-40 ns). The difference in ESIPT reactivity for 1-3 was fully
      disclosed by calculations at ADC(2)/aug-cc-pVDZ level of theory, and
      particularly, by calculation of charge redistribution upon excitation to S1. Only
      2,3-disubstituted anthrols exhibit polarization in S1 that increases the electron
      density on the carbonyl and decreases this density on the phenolic OH, setting
      the stage for ultrafast ESIPT.

PMID- 29039437
TI  - Silver-catalyzed decarboxylative acylation of quinoxalin-2(1H)-ones with alpha
      oxo-carboxylic acids.
AB  - A novel silver-catalyzed decarboxylative acylation of alpha-oxo-carboxylic acids
      was developed, by which various 3-acyl quinoxalin-2(1H)-ones were synthesized by
      direct C-H bond acylation of quinoxalin-2(1H)-ones. In this method, alpha-oxo
      carboxylic acids served as efficient acylating reagents to in situ generate the
      required active acyl radical. Its excellent chemoselectivity allowed the
      molecular diversity of 3-acyl quinoxalin-2(1H)-ones to be achieved by convenient
      functionalizations of both N1- and C3-positions.

PMID- 29039438
TI  - Chondroitin sulfate proteoglycans inhibit the migration and differentiation of
      oligodendrocyte precursor cells and its counteractive interaction with laminin.
AB  - Cerebral white matter injury (WMI) is a recognized problem in premature infants,
      particularly in those with very low birth weights. Although the survival rate of
      premature infants has notably increased due to the advancement of modern medical
      treatments, their likelihood of developmental disability is higher than infants
      with an average birth weight. It has been previously reported that
      oligodendrocyte precursor cells (OPCs) are selectively vulnerable to WMI in
      premature infants. Following brain injury, glial scars may develop within the
      white matter. Their main constituent is chondroitin sulphate proteoglycans
      (CSPGs), revealing a potential association between CSPGs and OPCs. In the present
      study rat OPCs were cultured in vitro, and the effect of CSPGs on the
      proliferation, migration and differentiation of OPCs was determined. It was
      revealed that CSPGs did not affect proliferation, but they did inhibit the
      migration and differentiation of OPCs. It was also identified that the inhibitory
      effect of CSPGs was counteracted by laminin. Factor analysis revealed that CSPGs
      and laminin served interactive roles in OPC differentiation. The effect of CSPGs
      on OPCs was associated with the downregulation of beta1-integrin, indicating that
      CSPGs potentially competitively inhibit the beta1-integrin signaling pathway.
      Collectively, these results suggest that CSPGs serve a role as inhibitors of OPC
      differentiation and migration, as well as indicating an interaction between CSPGs
      and laminin. The present study has revealed a potential novel therapeutic target
      for WMI in premature infants, and identified beta1-integrin signaling as a
      pathological mechanism for dysfunctional myelination in white matter.

PMID- 29039439
TI  - Naringin inhibits vascular endothelial cell apoptosis via endoplasmic reticulum
      stress- and mitochondrial-mediated pathways and promotes intraosseous
      angiogenesis in ovariectomized rats.
AB  - In this study, to investigate the effects of naringin on vascular endothelial
      cell (VEC) function, proliferation, apoptosis, and angiogenesis, rat VECs were
      cultured in vitro and randomly divided into four groups: control, serum-starved,
      low-concentration naringin treatment, and high-concentration naringin treatment.
      MTT assay was used to detect cell proliferation while Hoechst 33258 staining and
      flow cytometry were used to detect apoptosis. Changes in the expression of
      apoptosis-associated proteins [GRP78, CHOP, caspase-12, and cytochrome c (Cyt.c)]
      were detected using western blotting. JC-1 staining was employed to detect
      changes in mitochondrial membrane potential. Intracellular caspase-3, -8, and -9
      activity was determined by spectrophotometry. ELISA was used to detect endothelin
      (ET), and a Griess assay was used to detect changes in the expression of nitric
      oxide (NO) in culture medium. The study further divided an ovariectomized (OVX)
      rat model of osteoporosis randomly into four groups: OVX, sham-operated, low
      concentration naringin treatment (100 mg/kg), and high-concentration naringin
      treatment (200 mg/kg). After 3 months of treatment, changes in serum ET and NO
      expression, bone mineral density (BMD), and microvessel density of the distal
      femur (using CD34 labeling of VECs) were determined. At each concentration,
      naringin promoted VEC proliferation in a time- and dose-dependent manner.
      Naringin also significantly reduced serum starvation-induced apoptosis in
      endothelial cells, inhibited the expression of GRP78, CHOP, caspase-12, and Cyt.c
      proteins, and reduced mitochondrial membrane potential as well as reduced the
      activities of caspase-3 and -9. Furthermore, naringin suppressed ET in vitro and
      in vivo while enhancing NO synthesis. Distal femoral microvascular density
      assessment showed that the naringin treatment groups had a significantly higher
      number of microvessels than the OVX group, and that microvascular density was
      positively correlated with BMD. In summary, naringin inhibits apoptosis in VECs
      by blocking the endoplasmic reticulum (ER) stress- and mitochondrial-mediated
      pathways. Naringin also regulates endothelial cell function and promotes
      angiogenesis to exert its anti-osteoporotic effect.

PMID- 29039440
TI  - Betulinic acid induces apoptosis by regulating PI3K/Akt signaling and
      mitochondrial pathways in human cervical cancer cells.
AB  - Betulinic acid (BA), a potential anticancer compound, could induce apoptosis in
      human cervical cancer (HeLa) cells, but its mechanism has yet to be fully
      elucidated. The present study was focused on deciphering the detailed molecular
      mechanism of BA-induced apoptosis. In the present study, results indicated that
      BA was highly effective against HeLa cells via induction of time-dependent
      apoptosis, and the authors demonstrated that the BA treatment acted through
      downregulating a phosphatidylinositol 3-kinase (PI3K) subunit and suppressing the
      Akt phosphorylation at Thr308 and Ser473 after increasing the generation of
      intracellular reactive oxygen species. Then, BA induced cell cycle arrest at the
      G0/G1 phase, which was consistent with the cell cycle-related protein results in
      which BA significantly enhanced the expression of p27Kip and p21Waf1/Cip1 in HeLa
      cells. This target-specific inhibition was associated with mitochondrial
      apoptosis, as reflected by the increased expression of Bad and caspase-9, the
      generation of reactive oxygen species (ROS) and the decline in mitochondrial
      membrane potential. Moreover, preincubation of the cells with glutathione
      (antioxidant) blocked the process of apoptosis, prevented the phosphorylation of
      downstream substrates. These results established that ROS acted as a key factor
      to effect apoptosis by BA treatment in HeLa cells. Therefore, these findings
      demonstrated that BA induced apoptosis in HeLa cells by downregulating the
      expression of PI3K/Akt signaling molecules via ROS, and triggering a
      mitochondrial pathway.

PMID- 29039441
TI  - Rivaroxaban attenuates thrombosis by targeting the NF-kappaB signaling pathway in
      a rat model of deep venous thrombus.
AB  - Anticoagulant therapy is commonly used for the prevention and treatment of
      patients with deep venous thrombus. Evidence has shown that rivaroxaban is a
      potential oral anticoagulant drug for the acute treatment of venous
      thromboembolism. However, the rivaroxaban-mediated molecular mechanism involved
      in the progression of deep venous thrombosis has not been investigated. In the
      present study, we investigated the efficacy of rivaroxaban and the underlying
      signaling pathways in the prevention and treatment of rats with deep venous
      thrombosis. A rat model with deep vein thrombus formation was established and
      received treatment with rivaroxaban or PBS as control. The thrombin-activatable
      fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) were
      analyzed both in vitro and in vivo. The progression of thrombosis and stroke was
      evaluated after treatment with rivaroxaban or PBS. Nuclear factor-kappaB (NF
      kappaB) signaling pathway in venous endothelial cells and in the rat model of
      deep venous thrombus was assessed. The therapeutic effects of rivaroxaban were
      evaluated as determined by changes in deep venous thrombosis in the rat model.
      Our results showed that rivaroxaban markedly inhibited TAFI and PAI-1 expression
      levels, neutrophils, tissue factor, neutrophil extracellular traps (NETs),
      myeloperoxidase and macrophages in venous endothelial cells and in the rat model
      of deep venous thrombus. Expression levels of ADP, PAIs, von Willebrand factor
      (vWF) and thromboxane were downregulated in vein endothelial cells and in serum
      from the experimental rats. Importantly, the incidences of inferior vena cava
      filter thrombus were protected by rivaroxaban during heparin-induced thrombolysis
      deep venous thrombosis in the rat model. We observed that activity of the NF
      kappaB signaling pathway was inhibited by rivaroxaban in vein endothelial cells
      both in vitro and in vivo. Notably, immunohistology indicated that rivaroxaban
      attenuated deep venous thrombosis and the accumulation of inflammatory factors in
      the lesions in venous thrombus. Matrix metalloproteinase (MMP) expression and
      activity were downregulated in rivaroxaban-treated rats with deep venous
      thrombus. Rivaroxaban inhibited the elasticity of the extracellular matrix and
      collagen-elastin fibers. On the whole, these results indicate that rivaroxaban
      attenuates deep venous thrombus through MMP-9-mediated NF-kappaB signaling
      pathway.

PMID- 29039442
TI  - Angiogenic effects of apigenin on endothelial cells after hypoxia-reoxygenation
      via the caveolin-1 pathway.
AB  - In the present study, we aimed to elucidate whether apigenin contributes to the
      induction of angiogenesis and the related mechanisms in cell hypoxia
      reoxygenation injury. The role of apigenin was examined in human umbilical vein
      endothelial cell (HUVEC) viability, migration and tube formation in vitro. To
      investigate the related mechanisms, we used caveolin-1 short interfering RNA. The
      viability of HUVECs was measured using Cell Counting Kit-8 assays, HUVEC
      migration was analyzed by crystal violet staining, and a tube formation assay was
      performed using the branch point method. Expression of caveolin-1, vascular
      endothelial growth factor (VEGF), and endothelial nitric oxide synthase (eNOS) in
      HUVECs was examined by polymerase chain reaction and western blotting. Our data
      revealed that apigenin induced angiogenesis in vitro by increasing the tube
      formation ability of HUVECs, which was counteracted by caveolin-1 silencing.
      Compared to the NC group, Caveolin-1 and eNOS expression was upregulated by
      apigenin, whereas compared to the NC group, eNOS expression was increased upon
      caveolin-1 silencing. The expression of VEGF was increased by treatment with
      apigenin; however, compared to the NC group, caveolin-1 silencing did not affect
      VEGF expression, and apigenin did not increase VEGF expression in HUVECs after
      caveolin-1 silencing. These data suggest that apigenin may be a candidate
      therapeutic target for stroke recovery by promoting angiogenesis via the caveolin
      1 signaling pathway.

PMID- 29039443
TI  - Grape seed proanthocyanidins inhibit the proliferation, migration and invasion of
      tongue squamous cell carcinoma cells through suppressing the protein kinase
      B/nuclear factor-kappaB signaling pathway.
AB  - Tongue squamous cell carcinoma (TSCC) is the most common oral squamous cell
      carcinoma. Despite significant advances in combined therapies, the 5-year
      survival rate of patients with TSCC has not notably improved; this is due to
      regional recurrences and lymph node metastasis. Grape seed proanthocyanidins
      (GSPs) are consumed as dietary supplements worldwide and possess anticancer
      activity against several different types of cancer. However, their effect on TSCC
      and the underlying mechanisms by which they function remain unclear. In the
      present study, it was identified that GSPs significantly inhibited the viability
      and induced the apoptosis of Tca8113 cells in a dose-dependent manner. This was
      associated with a significantly increased expression of the pro-apoptosis
      regulator BAX protein and a significantly decreased expression of the anti
      apoptosis regulator Bcl-2 protein at 100 ug/ml GSPs. In addition, at non-toxic
      concentrations GSPs significantly inhibited the secretion of matrix
      metalloproteinase-2 (MMP-2) and MMP-9 from Tca8113 cells, as well as their
      migration and invasion. Furthermore, it was demonstrated that GSPs significantly
      inhibited the phosphorylation of protein kinase B (Akt) and IkappaB kinase, as
      well as the translocation of nuclear factor-kappaB (NF-kappaB) into the nucleus
      of Tca8113 cells. Taken together, these results suggest that GSPs inhibit the
      proliferation, migration and invasion of Tca8113 cells through suppression of the
      Akt/NF-kappaB signaling pathway. This indicates that GSPs may be developed as a
      novel potential chemopreventive agent against TSCC.

PMID- 29039444
TI  - Vaspin protects against LPS-induced ARDS by inhibiting inflammation, apoptosis
      and reactive oxygen species generation in pulmonary endothelial cells via the
      Akt/GSK-3beta pathway.
AB  - Acute respiratory distress syndrome (ARDS) is characterized by uncontrolled
      extravasation of protein-rich fluids, which is caused by disruption and
      dysfunction of the barrier of pulmonary endothelial cells (ECs). Visceral adipose
      tissue-derived serine protease inhibitor (vaspin) is a novel adipokine with
      pleiotropic properties, which has been reported to exert beneficial effects
      against obesity-associated systemic vascular diseases; however, its effects on
      ARDS remain unknown. In the present study, mice were subjected to systemic
      administration of adenoviral vector expressing vaspin (Ad-vaspin) to examine its
      effects on lipopolysaccharide (LPS)-induced ARDS in vivo. Histological analysis
      was then conducted, and cytokine [tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-6 and IL-10] levels, and intercellular cell adhesion molecule-1 (ICAM-1) and
      adherens junctions (AJs) expression were detected. In addition, human pulmonary
      microvascular ECs (HPMECs) were treated with recombinant human (rh)-vaspin to
      further investigate its molecular basis and underlying mechanism. The mRNA
      expression levels of inflammatory cytokines (TNF-alpha and IL-6) and endothelial
      specific adhesion markers [vascular cell adhesion molecule-1 and E-selectin],
      activation of nuclear factor-kappaB, and cell viability and apoptosis were then
      examined. Furthermore, the expression of AJs and organization of the
      cytoskeleton, as well as expression and activity of nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase and generation of reactive oxygen species
      (ROS) were determined. The results indicated that Ad-vaspin protected against LPS
      induced ARDS by alleviating the pulmonary inflammatory response and pulmonary EC
      barrier dysfunction in mice, which was accompanied by activation of the protein
      kinase B (Akt)/glycogen synthase kinase (GSK)-3beta pathway. In addition,
      pretreatment of HPMECs with rh-vaspin attenuated inflammation, apoptosis and ROS
      generation without alterations in AJs and cytoskeletal organization following LPS
      insult, which was accompanied by activation of the Akt/GSK3beta pathway. In
      conclusion, the present study demonstrated that vaspin protects against LPS
      induced ARDS by reversing EC barrier dysfunction via the suppression of
      inflammation, apoptosis and ROS production in pulmonary ECs, at least partially
      via activation of the Akt/GSK3beta pathway. These findings provide evidence of a
      causal link between vaspin and EC dysfunction in ARDS, and suggest a potential
      therapeutic intervention for patients with ARDS.

PMID- 29039445
TI  - Isoliquiritigenin suppresses IL-1beta induced apoptosis and inflammation in
      chondrocyte-like ATDC5 cells by inhibiting NF-kappaB and exerts chondroprotective
      effects on a mouse model of anterior cruciate ligament transection.
AB  - Isoliquiritigenin (ISL), a natural flavonoid extracted from licorice, has been
      demonstrated to exert attenuation of the nuclear factor-kappaB (NF-kappaB)
      signaling pathway and anti-inflammatory activity in a wide variety of cells. In
      the present study, the authors first evaluated the effects of ISL on cartilage
      degeneration in interleukin-1beta (IL-1beta)-stimulated chondrocyte-like ATDC5
      cells and in a mouse model of osteoarthritis (OA). The data of a cell counting
      kit-8 and flow cytometry assay indicated that ISL suppressed the inhibitory
      effect of IL-1beta on cell viability. The mRNA and protein expression levels of
      cyclooxygenase-2 and matrix metalloproteinase-13 were significantly decreased,
      while the expression of collagen II was increased, as indicated by RT-qPCR and
      western blot analysis following the chondrocyte-like ATDC5 cells were co
      intervened with IL-1beta and ISL for 48 h. Also, ISL attenuated protein
      expressions level of pro-apoptotic Bax, cleaved-caspase-3 and cleaved-caspase-9
      and promoted expression of anti-apoptotic Bcl-2. Moreover, ISL inhibited NF
      kappaB p65 phosphorylation induced by IL-1beta. In addition, ISL also increased
      improved the thickness of hyaline cartilage and the production of proteoglycans
      in the cartilage matrix in a mouse OA model. These results indicated that ISL
      exerted anti-inflammatory and anti-apoptotic effects on IL-1beta-stimulated
      chondrocyte-like ATDC5 cells, which may be associated with the downregulation of
      the NF-kappaB signaling pathway. In this way, the data supported the conclusion
      that ISL may be a novel potential preventive agent suitable for use in OA
      therapy.

PMID- 29039446
TI  - Protective effect of autophagy in neural ischemia and hypoxia: Negative
      regulation of the Wnt/beta-catenin pathway.
AB  - Autophagy is a highly conserved process of self-digestion to promote cell
      survival in response to nutrient starvation and other metabolic stresses.
      However, whether ischemic-hypoxic (IH) injury-induced autophagy acts as a
      neuroprotective mechanism or leads to neuroinjury is a subject of debate. It is
      known that autophagy is regulated by signaling pathways, including the mammalian
      target of rapamycin pathway. However, in neural IH injury, whether other
      signaling pathways are involved in the regulation of autophagy remains to be
      fully elucidated. In the present study, using the autophagy agonist (rampycin),
      autophagy antagonist [3-methyl adenine (3-MA)] and lysosome antagonist (MHY1485),
      autophagy was intervened with at oxygen-glucose deprivation (OGD) 6 h, in order
      to elucidate the regulatory mechanisms of autophagy. Using immunocytochemistry
      and western blot analysis, the expression levels of stress-related proteins, such
      as hypoxia-inducible factor-1alpha (HIF-1alpha) (a key regulator in hypoxia) and
      cyclooxygenase 2 (COX2; inflammatory indicator), were analyzed. In addition, the
      upstream proteins (Wnt1 and Wnt3a), downstream proteins (Dvl2, beta-catenin) and
      target proteins (C-myc and cyclin D) in the Wnt/beta-catenin signaling pathway
      were examined by immunocytochemistry and western blot analysis. The present study
      revealed that autophagy was activated with the upregulation of autophagic flux in
      IH injury; it was demonstrated that autophagy had a protective role in IH injury.
      The Wnt/beta-catenin pathway was involved in IH injury regulation, and the
      upstream proteins in the Wnt/beta-catenin signaling pathway were upregulated,
      whereas downstream proteins were downregulated by the activity of autophagy
      accordingly.

PMID- 29039447
TI  - Paralemmin-3 contributes to lipopolysaccharide-induced inflammatory response and
      is involved in lipopolysaccharide-Toll-like receptor-4 signaling in alveolar
      macrophages.
AB  - Alveolar macrophages (AMs) are the first line of defense against foreign
      stimulation in alveoli, and they participate in inflammatory responses during
      acute lung injury (ALI). Previous studies indicated that paralemmin-3 (PALM3)
      expression is induced by lipopolysaccharides (LPS) and may be involved in LPS
      Toll-like receptor 4 (TLR4) signaling in alveolar epithelial cells. The aim of
      the present study was to investigate the effect of PALM3 on LPS-induced
      inflammation and its underlying mechanisms in rat AMs. For this purpose, the
      authors detected the expression of PALM3 in AMs by reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) and western blotting following
      LPS stimulation. Following this, a recombinant adenovirus expressing short
      hairpin RNA (shRNA) for PALM3 was constructed, as well as a recombinant
      adenovirus carrying the rat PALM3 gene to modulate the expression of PALM3 in rat
      AMs. At 48 h after transfection, the PALM3 expression in AMs was detected by RT
      qPCR and western blotting. The levels of several cytokines and the activity of
      nuclear factor-kappaB and interferon regulatory factor 3 in AMs were measured
      after LPS stimulation. The localization of PALM3 and LPS-TLR4 signaling adaptor
      molecules in AMs was analyzed by confocal microscopy, and the physical
      interactions of PALM3 with these adaptors were assessed by co-immunoprecipitation
      assays. LPS induced PALM3 expression in AMs and that PALM3 expression promoted
      the LPS-induced inflammatory response, while PALM3 downregulation suppressed the
      LPS-induced inflammatory response in AMs. In addition, the results demonstrated
      that PALM3 could interact with TLR4, myeloid differentiation factor 88,
      interleukin (IL)-1 receptor associated kinase-1, tumor necrosis factor receptor
      associated factor-6, and Toll-IL-1 receptor containing adapter molecule-2 in AMs
      after LPS stimulation. These results suggested that PALM3 contributes to the LPS
      induced inflammatory response and participates in LPS-TLR4 signaling in AMs.
      These data may provide the basis for the development of novel targeted
      therapeutic strategies of treating ALI.

PMID- 29039448
TI  - Astragaloside IV attenuates the H2O2-induced apoptosis of neuronal cells by
      inhibiting alpha-synuclein expression via the p38 MAPK pathway.
AB  - An oxidative stress insult is one of the principal causes of Parkinson's disease.
      Astragaloside IV (AS-IV), a constituent extracted from Astragalus membranaceus,
      has been demonstrated to exert antioxidant effects. However, the mechanisms
      responsible for the antioxidant properties and neuroprotective effects of AS-IV
      remain unclear. In this study, we examined the protective effects of AS-IV
      against the apoptosis of human neuronal cells (SH-SY5Y cells) induced by hydrogen
      peroxide (H2O2). The results revealed that AS-IV pre-treatment attenuated the
      H2O2-induced loss of SH-SY5Y cells in a dose-dependent manner; AS-IV exerted
      significant protecitve effects by decreasing the apoptotic ratio and attenuating
      reactive oxygen species overproduction in H2O2-exposed SH-SY5Y cells. By means of
      immunofluorescence staining, AS-IV was found to decrease the expression of alpha
      synuclein and to increase the expression of tyrosine hydroxylase (TH) in the
      cells, which had been increased and decreased, respectively by H2O2. As shown by
      western blot analysis, the protective effects of AS-IV against SH-SY5Y cell
      injury induced by H2O2 were also mediated via the downregulation of the ratio of
      Bax/Bcl-2. We found that the neuroprotective effects of AS-IV were associated
      with the inhibition of the expression of the alpha-synuclein via the p38 mitogen
      activated protein kinase (MAPK) signalling pathway. On the whole, our results
      suggest that AS-IV exerts protective effects against neurodegenerative diseases
      by targeting alpha-synuclein or TH.

PMID- 29039450
TI  - Insulin restores UCP3 activity and decreases energy surfeit to alleviate
      lipotoxicity in skeletal muscle.
AB  - An early insulin regimen ameliorates glucotoxicity but also lipotoxicity in type
      2 diabetes; however, the underlying mechanism remains elusive. In the present
      study, we investigated the role of mitochondria in lipid regulation following
      early insulin administration in insulin-resistant skeletal muscle cells. Male
      C57BL/6 mice, fed a high-fat diet (HFD) for 8 weeks, were treated with insulin
      for 3 weeks, and L6 myotubes cultured with palmitate (PA) for 24 h were incubated
      with insulin for another 12 h. The results showed that insulin facilitated
      systemic glucose disposal and attenuated muscular triglyceride accumulation in
      vivo. Recovery of AMP-activated protein kinase (AMPK) phosphorylation, inhibition
      of sterol-regulated element binding protein-1c (SREBP-1c) and increased carnitine
      palmitoyltransferase-1B (CPT1B) expression were observed after insulin
      administration. Moreover, increased ATP concentration and cellular energy charge
      elicited by over-nutrition were suppressed by insulin. Despite maintaining
      respiratory complex activities, insulin restored muscular uncoupling protein 3
      (UCP3) protein expression in vitro and in vivo. By contrast, knockdown of UCP3
      abrogated insulin-induced restoration of AMPK phosphorylation in vitro.
      Importantly, the PA-induced decrease in UCP3 was blocked by the proteasome
      inhibitor MG132, and insulin reduced UCP3 ubiquitination, thereby prohibiting its
      degradation. Our findings, focusing on energy balance, provide a mechanistic
      understanding of the promising effect of early insulin initiation on
      lipotoxicity. Insulin, by recovering UCP3 activity, alleviated energy surfeit and
      potentiated AMPK-mediated lipid homeostasis in skeletal muscle cells following
      exposure to PA and in gastrocnemius of mice fed HFD.

PMID- 29039449
TI  - Crosstalk between TLR2 and Sphk1 in microglia in the cerebral
      ischemia/reperfusion-induced inflammatory response.
AB  - Stroke is associated with high morbidity and mortality, and much remains unknown
      about the injury-related mechanisms that occur following reperfusion. This study
      aimed to explore the roles of Toll-like receptor 2 (TLR2) and sphingosine kinase
      1 (Sphk1) in microglial cells in inflammatory responses induced by cerebral
      ischemia/reperfusion (I/R). For this purpose, C57BL/6 mice were randomly divided
      into 4 groups as follows: the sham-operated group, the I/R group, the I/R group
      treated with TLR2 antibody, and the I/R group treated with N,N
      dimethylsphingosine. Focal cerebral I/R was induced by middle cerebral artery
      occlusion. Double-labeling immunofluorescence was used to observe the protein
      expression of TLR2 and Sphk1 in the ischemic brain tissue. Quantitative
      polymerase chain reaction was performed to determine the mRNA levels of TLR2 and
      Sphkl in ischemic brain tissue. Enzyme-linked immunosorbent assay was carried out
      to detect the protein contents of interleukin (IL)-1beta, tumor necrosis factor
      alpha (TNF-alpha), IL-17 and IL-23 in ischemic brain tissue. The results revealed
      that I/R upregulated TLR2 and Sphk1 expression in microglial cells, and the
      inhibition of either TLR2 or Sphk1 inhibited the expression of the pro
      inflammatory cytokines, IL-1beta, TNF-alpha, IL-17 and IL-23. Notably, the
      inhibition of TLR2 activity also decreased Sphk1 expression. These results thus
      indicate that the activation of microglial cells, via a TLR2->Sphk1->pro
      inflammatory cytokine (IL-1beta, TNF-alpha, IL-17 and IL-23) pathway, may
      participate in I/R injury.

PMID- 29039451
TI  - Anti-inhibitory potential of an ethanolic extract of Distromium decumbens on pro
      inflammatory cytokine production in Pseudomonas aeruginosa lipopolysaccharide
      stimulated nasal polyp-derived fibroblasts.
AB  - Marine algae are rich sources of biologically active compounds that may present
      useful leads in the development of pharmaceuticals, nutraceuticals, and
      functional foods. The main aim of this study was to identify the possible anti
      inflammatory effects of Distromium decumbens in nasal polyp-derived fibroblasts
      (NPDFs) and its associated mechanism of action. NPDFs were stimulated by
      Pseudomonas aeruginosa lipopolysaccharide (PA-LPS) and treated with an ethanolic
      extract of Distromium decumbens (DDE). The production of interleukin-6 (IL-6) and
      IL-8 in the supernatant, the phosphorylation of mitogen-activated protein kinase
      (MAPK) molecules [extracellular signal-related kinase 1/2 (ERK1/2), c-Jun N
      terminal kinase and p38 MAPK] and Akt, and the activation of nuclear factor
      kappaB (NF-kappaB) were assayed in the PA-LPS-stimulated NPDFs untreated or
      treated with DDE. The expression levels of IL-6 and IL-8 in PA-LPS-exposed NPDFs
      were detected using enzyme-linked immunosorbent assays. The mechanisms by which
      DDE regulates cellular signaling cascades were investigated using electrophoretic
      mobility shift assays and western blot analysis. Functional validation was
      performed by measuring the inhibitory effects of DDE on neutrophil migration in
      vitro. DDE reduced the expression of IL-6 and IL-8 stimulated by PA-LPS in NPDFs.
      The activation of ERK1/2, Akt and NF-kappaB by PA-LPS was inhibited by DDE.
      Inhibitors of ERK1/2, Akt and NF-kappaB inhibited the expression of IL-6 and IL
      8. In addition, DDE significantly attenuated PA-LPS-induced migration of
      differentiated HL-60 cells. The present findings suggest that DDE potently
      inhibits inflammation through the ERK1/2, Akt and NF-kappaB signaling pathways in
      NPDFs.

PMID- 29039452
TI  - Molecular analysis of keratocystic odontogenic tumor cell lines derived from
      sporadic and basal cell nevus syndrome patients.
AB  - Keratocystic odontogenic tumor (KCOT) is a benign tumor often associated with
      basal cell nevus syndrome (BCNS). Mutations in Patched 1 (PTCH1), the Hedgehog
      (Hh) receptor, are responsible for BCNS. BCNS is distinguished by morphological
      anomalies and predisposition to benign and malignant tumors, including
      medulloblastoma, basal cell carcinoma, KCOT and ovarian fibromas. Among these
      tumors, KCOT is the least well studied because a suitable model system is not
      available for its investigation. To enable KCOT to be studied, we established two
      KCOT cell lines, one from a BCNS case (designated as iKCOT1) and one from a
      sporadic KCOT case (designated as sKCOT1). The BCNS-derived KCOT cell line,
      iKCOT1, retained a germline-mutated PTCH1 allele and a wild-type PTCH1 allele.
      The sporadic KCOT-derived KCOT cell line, sKCOT1, had different loss-of-function
      PTCH1 mutations on both alleles. Both cell lines expressed stem cell markers
      (CD44, SOX2 and BMI1), mesenchymal cell markers (CDH2, VIM and SNAI2) and a
      neurogenic marker (NEFL). Culture of the cell lines in high calcium concentration
      media induced expression of epithelial cell and keratinocyte marker proteins
      (CDH1, CLDN1, KRT10 and IVL). Parakeratosis, which is characteristic for KCOTs,
      was observed in 2-D cultures. The similarities in protein expression patterns
      between the two cell lines suggested that common mechanisms underlie the
      development of both types of KCOT and a probable common origin of KCOT cells.

PMID- 29039453
TI  - MicroRNA-125a-3p is involved in early behavioral disorders in stroke-afflicted
      rats through the regulation of Cadm2.
AB  - Ischemic strokes carry a significant risk of mortality and recurrent vascular
      events. Recent studies suggest that changes in microRNAs (miRNAs or miRs) may
      affect the development of the stroke. However, few studies have investigated the
      role of miRNAs in behavioral disorder in early stroke. In the present study,
      animal models of middle cerebral artery occlusion (MCAO) are used, as well as a
      cell model of neurite outgrowth to further investigate the role of miRNAs in
      targeting synapse-associated proteins expression in early stroke. The authors
      used miRNA expression microarrays on RNA extracted from the cortex tissue samples
      from the rats of MCAO and control rats. Reverse transcription-quantitative
      polymerase chain reaction was conducted to verify the candidate miRNAs discovered
      by microarray analysis. Data indicated that miR-125a was significantly increased
      in the cortex of the model of MCAO, which were concomitant with that rats of MCAO
      at the same age displayed significant behavioral deficits. Bioinformatics
      analysis predicted the cell adhesion molecule 2 (Cadm2, mRNA) neurite outgrowth
      associated protein is targeted by miR-125a. Overexpression of miR-125a reduced
      the level of Cadm2 expression in PC12 cell injury induced by free-serum. In
      contrast, inhibition of miR-125a using miR-125a inhibitors significantly resulted
      in higher levels of Cadm2 expression. In conclusion, miR-125a is involved in the
      behavioral disorder of animal models of MCAO by regulation of Cadm2.

PMID- 29039454
TI  - SOX4 arrests lung development in rats with hyperoxia-induced bronchopulmonary
      dysplasia by controlling EZH2 expression.
AB  - Bronchopulmonary dysplasia (BPD) is currently the most common severe complication
      in premature infants and is characterized by the arrest of alveolar and vascular
      growth. Alveolar type II cells play an important role in the pathological
      foundation of BPD. An association of BPD with epithelial-to-mesenchymal
      transition (EMT) in type II cells exposed to hyperoxia was previously identified.
      SOX4, a transcription factor that is indispensable to embryogenesis, including
      lung development, participates in regulating EMT and cell survival, affecting
      tumorigenesis. The aim of the present study was to investigate the involvement of
      SOX4 in the occurrence of BPD, which, to the best of our knowledge, has not been
      previously determined. For this purpose, newborn rats were randomly divided into
      two treatment groups: The model group was exposed to hyperoxia (80-85% O2), while
      the control group was kept under normoxic conditions (21% O2). Lung tissues were
      collected on postnatal days 1, 3, 7, 14 and 21 and morphological changes in the
      lungs were examined by hematoxylin and eosin staining. The location of SOX4 in
      type II cells was detected by double immunofluorescence. The expression of SOX4
      and enhancer of zeste homolog 2 (EZH2) in type II cells and lung tissues were
      detected by immunochemistry, western blotting and quantitative polymerase chain
      reaction analysis. The results demonstrated that, compared with the control
      group, the radial alveolar count decreased rapidly in the model group,
      accompanied by increased mean alveolar diameter and alveolar septal thickness.
      SOX4 and EZH2 were highly expressed in type II cells exposed to hyperoxia.
      However, in total lung tissues, SOX4 and EZH2 expression was profoundly decreased
      in the early stages and increased in the late stages following exposure to
      hyperoxia. The expression of the EZH2 protein was positively correlated with that
      of the SOX4 protein. In conclusion, at the alveolar stage, which is a critical
      period after birth for lung development, hyperoxia induced dysregulation of SOX4
      and EZH2 in rat lungs, indicating that SOX4 may contribute to the disruption of
      lung development in BPD by regulating EZH2 expression.

PMID- 29039455
TI  - Cell-penetrating peptides and their utility in genome function modifications
      (Review).
AB  - For almost 30 years, studies have confirmed the effectiveness of cell-penetrating
      peptides (CPPs) in the facilitation of the intracellular delivery of various
      cargo molecules, including RNA, DNA, plasmids, proteins or nanoparticles, under
      in vitro and in vivo conditions. The cellular uptake of CPPs occurs via energy
      dependent, as well as -independent mechanisms. In this relatively new direction
      of research, studies have attempted to introduce genome modification systems into
      cells by CPPs. Cellular uptake of CPPs carrying either covalently bound or
      electrostatically conjugated cargo, has several advantages over viral delivery
      systems, as it does not lead to any significant cytotoxicity or immunogenicity,
      and simultaneously it is more efficient than other non-viral systems. So far,
      CPPs have been successfully used to introduce Cre recombinase, zinc finger
      nucleases, transcription activator-like effector nucleases and clustered
      regularly interspaced short palindromic repeats systems into cells. The present
      article systematically reviewed the information obtained from studies on CPPs and
      assessed their utility with regard to their effectiveness and safety of use.

PMID- 29039456
TI  - Construction of a Bcl-2-shRNA expression vector and its effect on the
      mitochondrial apoptosis pathway in SW982 cells.
AB  - Apoptosis is considered to serve an important role in the pathogenesis of
      rheumatoid arthritis. The aim of the present study was to construct Bcl-2-short
      hairpin (sh)RNA expression vectors and transfect them into human synovial sarcoma
      SW982 cells, in order to screen for an effective interference sequence and
      analyze the effects of this interference on the expression levels of Bcl-2 and
      other molecules associated with the mitochondrial apoptosis pathway. Three
      different shRNAs (Bcl-2-sh1, 2 and 3) were designed according to the human Bcl-2
      mRNA target sequence and were transformed into competent DH5alpha Escherichia
      coli cells following the construction of an expression vector, which was then
      transfected into SW982 cells. SW982 cells were grouped into a control group
      (transfected with a negative control shRNA), and Bcl-2-sh1, Bcl-2-sh2 and Bcl-2
      sh3 groups (transfected with Bcl-2-sh1, 2 and 3, respectively). The expression
      levels of Bcl-2 mRNA were detected using reverse transcription-quantitative PCR
      (RT-qPCR). Bcl-2-sh1 was identified as the most effective shRNA sequence for
      interference, and was used for subsequent experiments. The mRNA and protein
      expression levels of Bcl-2, Bax, CytC and Caspase-3 were detected in SW982 cells
      by RT-qPCR and western blotting at various time-points (48 and 72 h) following
      transfection with Bcl-2-sh1, in order to observe the effectiveness of this
      interference. Compared with the control group, the expression levels of Bcl-2
      were decreased, while those of Bax, CytC and Caspase-3 were increased in Bcl-2
      sh1-transfected cells (P<0.01). The interference effect was greater at 48 h than
      at 72 h. In summary, an effective shRNA sequence (Bcl-2-sh1) targeting the Bcl-2
      gene was identified from three candidates, and was demonstrated to significantly
      interfere with the expression of Bcl-2, Bax, CytC and Caspase-3 when transfected
      into SW982 cells. The interference effect of Bcl-2-sh1 was more pronounced at 48
      h than at 72 h post-transfection.

PMID- 29039458
TI  - DNA polymerase 5 acetylation by Eso1 is essential for Schizosaccharomyces pombe
      viability.
AB  - Eco1/Eso1 protein plays an important role in chromosome segregation, DNA repair
      and gene regulation. Eco1 mutation induces Roberts syndrome clinically and rDNA
      transcription disorders in vivo. In this study, we examined the role of Eso1
      protein binding to polymerase 5 (Pol5) and the acetylation of Pol5 protein in the
      regulation of Schizosaccharomyces pombe (S. pombe) viability. Immunoprecipitation
      and mass spectrometry assays identified Eso1 protein binding to Cdc2, Pol5 and
      Cdc21, as well as other proteins. Pol5 protein specifically bound to Eso1
      protein, but not to the Rad30 part or Rad30 part plus the additional zinc finger
      domain of Eco1 protein. Mass spectrometry data further identified several
      acetylation or trimethylation modification sites in the lysine residues of the
      Pol5 protein. However, the mutation of the Pol5 K47 site to arginine was lethal
      to S. pombe. Eso1 protein was able to acetylate Pol5 protein and mediate S. pombe
      viability. On the whole, our data indicate that the Eso1 interaction with Pol5
      which acetylates Pol5 protein is essential for S. pombe viability.

PMID- 29039457
TI  - High-throughput sequencing reveals novel lincRNA in age-related cataract.
AB  - Age-related cataract (ARC) is a major cause of blindness. Long non-coding RNAs
      (lncRNAs) are a heterogeneous class of RNAs that are non-protein-coding
      transcripts >200 nucleotides in length. LncRNAs are involved in various critical
      biological processes, such as chromatin remodeling, gene transcription, and
      protein transport and trafficking. Furthermore, the dysregulation of lncRNAs
      causes a number of complex human diseases, including coronary artery diseases,
      autoimmune diseases, neurological disorders and various cancers. However, the
      role of lncRNA in cataract remains unclear. Therefore, in the present study, lens
      anterior capsular membrane was collected from normal subjects and patients with
      ARC and total RNA was extracted. High-throughput sequencing was applied to detect
      differentially expressed lncRNAs and mRNAs. The analysis identified a total of
      42,556 candidate differentially expressed mRNAs (27,447 +15,109) and a total of
      7,041 candidate differentially expressed lncRNAs (4,146 + 2,895). Through
      bioinformatics analysis, the significant differential expression of novel lincRNA
      was observed and its possible molecular mechanism was explored. Reverse
      transcription-quantitative polymerase chain reaction was used to validate the
      different expression levels of selected lncRNAs. These findings may lead to the
      development of novel strategies for genetic diagnosis and gene therapy.

PMID- 29039459
TI  - BC-02 eradicates liver cancer stem cells by upregulating the ROS-dependent DNA
      damage.
AB  - Cancer stem cells (CSCs) are responsible for chemoresistance, tumor recurrence
      and metastasis. Reportedly, aminopeptidase N (APN, also known as CD13) is a
      marker for semi-quiescent CSCs and a therapeutic target in human liver CSCs. In
      the present study, the effect of BC-02, a compound obtained by conjugating a CD13
      inhibitor bestatin and fluorouracil (5-FU), was investigated toward liver CSCs.
      Tumor spheres formed in serum-free culture conditions have been successfully used
      to enrich CSCs. In this study, the sphere cells were shown to have several
      characteristics of CSCs, including drug resistance, high tumorigenicity,
      epithelial-mesenchymal transition (EMT) phenotype, lower reactive oxygen species
      (ROS) levels, greater colony-forming efficiency and increased proliferation
      capacity in vitro. Furthermore, BC-02 effectively suppressed self-renewal and
      malignant proliferation of CSCs compared with 5-FU, bestatin, and even the
      combination of 5-FU and bestatin. In addition, cell proliferation was effectively
      suppressed when exposed to 5-FU plus CD13-neutralizing antibody (CD13 Ab)
      compared with 5-FU alone. BC-02 can effectively inhibit the activity of CD13.
      Results demonstrated that CD13 inhibitor BC-02 impaired the properties of liver
      CSCs by targeting CD13 and upregulating the intracellular ROS and ROS-induced DNA
      damage. BC-02 might be a potential therapeutic agent for eradicating the liver
      CSCs and overcoming chemoresistance in liver cancer.

PMID- 29039460
TI  - Characterization of tree shrew (Tupaia belangeri) interleukin-6 and its
      expression pattern in response to exogenous challenge.
AB  - Tree shrews, one of the closest relatives of primates, have attracted increasing
      attention as a model of human diseases, particularly for viral infections. As the
      first line of defense against microbial pathogens, the innate immune system is
      crucial in tree shrews. Interleukin-6 (IL-6) is important in the pathophysiology
      of infection, inflammation and cancer, where it promotes disease development or
      sustains immune reactions. The present study aimed to obtain further insight into
      the tree shrew IL-6 (tsIL-6) system, and the function of tsIL-6 in the antiviral
      and antibacterial response. In the present study, the mRNA and genomic sequence
      of the tsIL-6 gene were characterized, and the tissue distribution and expression
      profile of this gene were analyzed in response to lipopolysaccharide (LPS) and
      polyinosinic:polycytidylic acid (poly I:C) treatment. The full-length tsIL-6 mRNA
      consisted of 1,152 bp with an open reading frame of 627 bp encoding 208 amino
      acids, a 5'-untranslated region (UTR) of 62 bp, and a 3'-UTR of 436 bp. The
      genome sequence of the tsIL-6 gene was 5,265 bp in length, comprising of five
      exons and four introns. The predicted tsIL-6 protein contained a 25-amino-acid
      long signal peptide and a conserved IL-6 domain. Phylogenetic analysis based on
      the coding sequences revealed that tsIL-6 was closely related to IL-6 in humans.
      Residues crucial for receptor binding were completely conserved in the tree shrew
      protein. Reverse transcription-polymerase chain reaction analysis revealed that
      tsIL-6 mRNA was expressed in all examined tissues of healthy tree shrews, with
      high levels in the muscle and spleen. Following poly I:C challenge, the
      expression levels of tsIL-6 were upregulated in four tissues associated with
      immune system, the liver, spleen, kidney and intestine. Taken together, the
      molecular and bioinformatics analyses based on the IL-6 sequence revealed that
      the tree shrew has a close phylogenetic association with humans. These results
      provide insight for future investigations on the structure and function of tsIL
      6.

PMID- 29039462
TI  - Antiproliferative activity of di-2-pyridylhydrazone dithiocarbamate acetate
      partly involved in p53 mediated apoptosis and autophagy.
AB  - Cancer cells have higher demand of iron and copper ions for growth, disturbing
      the metal's homeostasis can inhibit proliferation of cancer cell.
      Dithiocarbamates possessing excellent metal chelating ability and antitumor
      activity are considered as candidates in chelation therapy, however, their
      antitumor molecular mechanisms remain to be elucidated. In the present study, a
      dithiocarbamate derivative, di-2-pyridylhydrazone dithiocarbamate s-acetic acid
      (DpdtaA) was prepared to address the issue whether the molecular mechanism behind
      biological behavior showed by dithiocarbamate was p53 mediated. The proliferation
      inhibition assay showed that DpdtaA exhibited excellent antiproliferative effect
      for hepatocellular carcinoma (IC50= 3.0+/-0.4 uM for HepG2, 6.1+/-0.6 uM for Bel
      7402 cell). However, in the presence of copper ion, the antiproliferative
      activity of DpdtaA significantly attenuated (~3-fold for HepG2) due to formation
      of copper chelate. The ROS assay revealed that the antiproliferative activity of
      DpdtaA correlated with ROS generation. Western blotting demonstrated that DpdtaA
      could upregulate p53 via down-regulating the Mdm2, accordingly leading to changes
      of bcl family proteins, indicating that a p53-dependent intrinsic apoptosis was
      partly involved. Simulation from molecular docking hinted that DpdtaA could
      disrupt interaction between p53 and Mdm2, indicating the disruption might also
      contribute to the upregulation of p53. The alternations in lysosome membrane
      permeability and acidic vacuoles as well as LC3-II upregulation indicated that
      autophagy was involved. The copper addition led to significantly attenuate
      biological activity of DpdtaA, with few dithiocarbamates, but the mechanism in
      apoptosis induction was not altered except for weaker ability.

PMID- 29039461
TI  - Effects of ursolic and oleanolic on SK-MEL-2 melanoma cells: In vitro and in vivo
      assays.
AB  - Among the triterpenoids, oleanolic acid (OA) and its isomer, ursolic acid (UA)
      are promising therapeutic candidates, with potential benefits in the management
      of melanoma. In this study, we aimed to examine the in vitro and in vivo anti
      invasive and anti-metastatic activity of OA and UA to determine their possible
      usefulness as chemopreventive or chemotherapeutic agents in melanoma. For the in
      vitro experiments, the anti-proliferative activity of the triterpenic compounds
      on SK-MEL-2 melanoma cells was examined. The anti-invasive potential was assessed
      by testing the effects of the active compound on vascular cell adhesion molecule
      (VCAM) and intercellular adhesion molecule (ICAM) adhesion to melanoma cells.
      Normal and tumor angiogenesis were evaluated in vivo by chicken embryo
      chorioallantoic membrane (CAM) assay. The two test triterpenoid acids, UA and OA,
      exerted differential effects in vitro and in vivo on the SK-MEL-2 melanoma cells.
      UA exerted a significant and dose-dependent anti-proliferative effect in vitro,
      compared to OA. The cytotoxic effects in vitro on the melanoma cells were
      determined by the examining alterations in the cell cycle phases induced by UA
      that lead to cell arrest in the S phase. Moreover, UA was found to affect SK-MEL
      2 melanoma cell invasiveness by limiting the cell adhesion capacity to ICAM
      molecules, but not influencing their adhesion to VCAM molecules. On the whole, in
      this study, by assessing the effects of the two triterpenoids in vivo, our
      results revealed that OA had a greater potential to impair the invasive capacity
      and tumor angiogenesis compared with UA.

PMID- 29039463
TI  - Hepatic differentiation of human iPSCs in different 3D models: A comparative
      study.
AB  - Human induced pluripotent stem cells (hiPSCs) are a promising source from which
      to derive distinct somatic cell types for in vitro or clinical use. Existent
      protocols for hepatic differentiation of hiPSCs are primarily based on 2D
      cultivation of the cells. In the present study, the authors investigated the
      generation of hiPSC-derived hepatocyte-like cells using two different 3D culture
      systems: A 3D scaffold-free microspheroid culture system and a 3D hollow-fiber
      perfusion bioreactor. The differentiation outcome in these 3D systems was
      compared with that in conventional 2D cultures, using primary human hepatocytes
      as a control. The evaluation was made based on specific mRNA expression, protein
      secretion, antigen expression and metabolic activity. The expression of alpha
      fetoprotein was lower, while cytochrome P450 1A2 or 3A4 activities were higher in
      the 3D culture systems as compared with the 2D differentiation system. Cells
      differentiated in the 3D bioreactor showed an increased expression of albumin and
      hepatocyte nuclear factor 4alpha, as well as secretion of alpha-1-antitrypsin as
      compared with the 2D differentiation system, suggesting a higher degree of
      maturation. In contrast, the 3D scaffold-free microspheroid culture provides an
      easy and robust method to generate spheroids of a defined size for screening
      applications, while the bioreactor culture model provides an instrument for
      complex investigations under physiological-like conditions. In conclusion, the
      present study introduces two 3D culture systems for stem cell derived hepatic
      differentiation each demonstrating advantages for individual applications as well
      as benefits in comparison with 2D cultures.

PMID- 29039464
TI  - Hypothermia inhibits the proliferation of bone marrow-derived mesenchymal stem
      cells and increases tolerance to hypoxia by enhancing SUMOylation.
AB  - Hypothermia therapy has a positive effect on patients with severe brain injury.
      Recent studies have shown that mild hypothermia increases the survival of bone
      marrow-derived mesenchymal stem cells (BMSCs) in a hypoxic environment; however,
      the underlying mechanisms are not yet fully understood. Small ubiquitin-like
      modifiers (SUMOs) are sensitive to temperature stress reactions and are
      considered to exert a protective effect. In this study, we examined the
      protective effects of hypothermia on BMSCs in terms of SUMO protein modification.
      First, we found that mild hypothermia inhibited the proliferation and
      differentiation of BMSCs and increased cell tolerance to a hypoxic environment.
      Second, hypothermia significantly increased the levels of SUMO modification of
      multiple proteins in BMSCs. The knockdown of SUMO1/2/3 induced the rapid aging of
      the BMSCs, while the inhibition of the SUMO-conjugating enzyme, Ubc9, reduced
      cell proliferation and increased the proportion of BMSCs differentiating into
      nerve cells. Moreover, the tolerance of BMSCs to the hypoxic environment was
      significantly decreased. Lastly, we investigated 4 reported SUMO target proteins,
      anti-proliferating cell nuclear antigen, octamer-binding transcription factor 4,
      p53 and hypoxia-inducible factor-1alpha, to confirm that SUMO modification was
      indeed involved in maintaining the proliferation, inhibiting differentiation and
      enhancing the resistance of BMSCs against adverse conditions. Taken together, our
      results indicate that the SUMO pathway is involved in the response to hypothermic
      stress, and that SUMOylation may be an important protective mechanism against
      hypothermia for the survival of BMSCs under unfavorable conditions.

PMID- 29039465
TI  - Essential role of microRNA-650 in the regulation of B-cell CLL/lymphoma 11B gene
      expression following transplantation: A novel mechanism behind the acute
      rejection of renal allografts.
AB  - Kidney transplantation is an effective final therapeutic procedure for patients
      with end-stage kidney failure. Although advanced immunosuppressive therapy is
      administered following transplantation, certain patients still suffer from acute
      allograft rejection. MicroRNAs (miRs) have a potential diagnostic and therapeutic
      value for acute renal allograft rejection; however, their underlying mechanism of
      action is largely unknown. In the present study, an increased level of miR-650
      was identified to be associated with the downregulation of B-cell CLL/lymphoma
      11B (BCL11B) expression in acute renal allograft rejection. Furthermore, in vitro
      study using human renal glomerular endothelial cells (HRGECs) transfected with a
      miR-650 mimic revealed that key characteristics of acute renal allograft
      rejection were observed, including apoptosis, the release of cytokines and the
      chemotaxis of macrophages, while the effects were reduced in HRGECs transfected
      with a miR-650 inhibitor. The existence of a conserved miR-650 binding site on
      the 3'-untranslated region of BCL11B mRNA was predicted by computational
      algorithms and confirmed by a luciferase reporter assay. Knockdown of BCL11B with
      small interfering RNA (siRNA) significantly increased the apoptotic rate and
      significantly decreased the proliferation ability of HRGECs compared with the
      negative control group. HRGECs transfected with a combination of BCL11B siRNA and
      the miR-650 mimic demonstrated a significant increase in the rate of apoptosis
      compared with the control. These results suggest that the upregulation of miR-650
      contributes to the development of acute renal allograft rejection by suppression
      of BCL11B, which leads to apoptosis and inflammatory responses. Thus, miR-650 and
      BCL11B may represent potential therapeutic targets for the prevention of acute
      renal allograft rejection.

PMID- 29039466
TI  - RACK1 silencing attenuates renal fibrosis by inhibiting TGF-beta signaling.
AB  - The receptor for activated C-kinase 1 (RACK1) is a member of the WD40-repeat
      family of proteins and has been reported to be implicated in the development of
      liver fibrosis. However, the role of RACK1 in renal fibrosis remains unclear.
      Therefore, in this study, we investigated the effects of RACK1 on transforming
      growth factor-beta1 (TGF-beta1)-treated human proximal tubular epithelial cells
      and aimed to elucidate the possible mechanisms responsible for its anti-fibrotic
      effects. Our results revealed that RACK1 was highly expressed in the renal
      fibrotic tissues and TGF-beta1-treated HK-2 cells. RACK1 silencing inhibited TGF
      beta1-induced alpha-smooth muscle actin and connective tissue growth factor
      expression in the HK-2 cells. Furthermore, RACK1 silencing inhibited the
      expression of phosphorylated Smad3 in the TGF-beta1-treated HK-2 cells. To the
      best of our knowledge, these data demonstrate for the first time the role of
      RACK1 in renal fibrosis. The present findings indicate that RACK1 silencing
      attenuates renal fibrosis by suppressing the activation of TGF-beta1/Smad3
      signaling pathway in HK-2 cells. Thus, RACK1 may serve as a novel regulator of
      renal fibrosis.

PMID- 29039467
TI  - Insulin-like growth factor binding protein-6 released from human mesenchymal stem
      cells confers neuronal protection through IGF-1R-mediated signaling.
AB  - Human bone marrow-derived mesenchymal stem cells (hMSCs) are a desirable cell
      source for cell-based therapy to treat nervous system injuries due to their
      ability to differentiate into specific cell types. In addition to their
      multipotency, hMSCs render the tissue microenvironment more favorable for tissue
      repair by secreting various growth factors. Our previous study demonstrated that
      hMSCs secrete several growth factors, including several insulin-like growth
      factor binding proteins (IGFBPs). Among these, IGFBP-6 binds with high affinity
      and inhibits insulin growth factor-2 (IGF-2) to inhibit the growth of IGF-2
      dependent tumors. However, the function of IGFBP-6 in the nervous system remains
      to be fully elucidated. The present study investigated the protective effects of
      IGFBP-6 secreted by hMSCs on H2O2-injured primary cortical neuron cultures and
      lysolecithin-injured organotypic spinal cord slice cultures. Treatment of the
      H2O2-injured cortical neurons with conditioned media from hMSCs (hMSC-CM)
      increased the phosphorylation of Akt, reduced cell death and mitochondrial
      translocation of Bax, and regulated extracellular levels of IGF-1 and IGF-2. MTT
      assay, western blot analysis and ELISA were used to detect the cell viability and
      protein expression levels, respectively. An inhibitory antibody against IGFBP-6
      eliminated this hMSC-CM-mediated neuroprotective effect in the injured cortical
      neuron cultures and spinal cord slice cultures. In addition, treatment with
      cyclolignan picropodophyllin, an inhibitor of IGF-1 receptor (IGF-1R),
      significantly inhibited neuronal protection by hMSC-CM. These findings
      demonstrated that hMSC-CM-mediated neuroprotection was attributed to IGF-1R
      mediated signaling, potentiated via the inhibition of IGF-2 by IGFBP-6. The
      results of the present study provide insight into the mechanism by which hMSC
      administration may promote recovery from nerve injury.

PMID- 29039468
TI  - Limited activation of the intrinsic apoptotic pathway plays a main role in
      amyloid-beta-induced apoptosis without eliciting the activation of the extrinsic
      apoptotic pathway.
AB  - Amyloid-beta (Abeta), a main pathogenic factor of Alzheimer's disease (AD),
      induces apoptosis accompanied by caspase activation. However, limited caspase
      activation and the suppression of the intrinsic apoptotic pathway (IAPW) are
      frequently observed upon Abeta treatment. In this study, we investigated whether
      these suppressive effects of Abeta can be overcome; we also examined the death
      related pathways. Single treatments of cells with Abeta42 for up to 48 h barely
      induced caspase activation. In cells treated with Abeta42 twice for 2 h followed
      by 22 h (2+22 h) or for longer durations, the apoptotic protease activating
      factor-1 (Apaf-1) apoptosome was formed and caspases-3 and -9 were activated to a
      certain extent, suggesting the activation of the IAPW. However, the Abeta42
      induced activation of the IAPW differed from that induced by treatment with other
      agents, such as staurosporine (STS) in that lower amounts of cytochrome c were
      released from the mitochondria, the majority of procaspase-9 in the Apaf-1
      complex was not processed and caspase-3 was activated to a lesser extent in the
      peptide-treated cells. Thus, it seemed that the IAPW was not fully activated by
      Abeta42. The 30- and 41/43-kDa fragments derived from procaspase-8 were detected,
      which appear to be produced through the IAPW without death-inducing signaling
      complex (DISC) formation, a key feature of the extrinsic apoptotic pathway
      (EAPW). Bid cleavage was observed only after caspase-3 activity reached its
      maximal levels, suggesting that the cleavage may contribute in a limited capacity
      to the amplification process of the IAPW in the Abeta-treated cells. Taken
      together, our data suggest that the IAPW, albeit functional only to a limited
      extent, plays a major role in Abeta42-induced apoptosis without the EAPW.

PMID- 29039469
TI  - The association of LMP7 and TAP2 gene polymorphisms with treatment response to
      interferon/ribavirin in patients with genotype 1 chronic hepatitis C.
AB  - Previous studies have highlighted the important role of genes related to antigen
      presentation in the spontaneous clearance of hepatitis C virus. The present study
      aimed to explore the association between TAP, LMP and tapasin gene polymorphism
      and treatment response in chronic hepatitis C virus (CHC) patients. Six single
      nucleotide polymorphisms in TAP, LMP and tapasin genes were genotyped among 352
      Chinese genotype 1 CHC patients with pegylated interferon-alpha and ribavirin
      (pegIFN-alpha/RBV) treatment. There were 232 cases achieving sustained
      virological response (SVR), which yielded an SVR rate of 65.9%. LMP7 rs2071543
      variant genotypes [additive model: odds ratio (OR), 0.52; 95% confidence interval
      (CI), 0.33-0.82; P=0.005] and TAP2 rs1800454 variant genotypes (additive model:
      OR, 0.66; 95% CI, 0.45-0.98; P=0.039) were suggested to decrease the possibility
      of achieving an SVR. After conducting combined effect analysis of rs2071543 and
      rs1800454, the authors found that the SVR rate was lower among patients carrying
      more unfavorable rs1800454-A and rs2071543-A alleles, and the SVR rate of
      carrying 3-4 alleles was 20%. In addition, carrying two unfavorable alleles led
      to significantly decreased possibility for SVR (OR, 0.30; 95% CI, 0.14-0.61;
      P=0.001). Multivariate stepwise analysis indicated that rs2071543, rs1800454,
      glucose, alpha-fetoprotein, platelets and baseline viral load were risk factors
      of SVR that were independent of each other. The area under the curve (AUC)
      consisting of all the above factors produced an AUC of 0.704 (95% CI, 0.647
      0.761; P<0.001). The line charts indicated that the drop in viral load was
      significantly faster in GG patients than in GC/CC patients during the whole
      therapy, which was in accordance with the decline of viral load in rs2071543. The
      present study illustrated that the carriage of LMP7 rs2071543-AA and TAP2
      rs1800454-AA had a negative effect on treatment response to pegIFN-alpha/RBV
      among genotype 1 patient with CHC in a Chinese Han population.

PMID- 29039470
TI  - Effects of baicalein on proliferation, apoptosis, migration and invasion of
      Ewing's sarcoma cells.
AB  - Ewing's sarcoma (ES) is a rare tumor that is more frequent in pediatric and
      adolescent age groups. In the past few decades, long-term survival in affected
      patients has improved due to the success of multimodal therapy. However, long
      term survival is inevitably restricted by the late side-effects of chemotherapy.
      Besides, early metastasis also contributes to the poor prognosis of ES. Recently,
      traditional Chinese medicines (TCMs) have increasingly attracted interest due to
      the promising clinical results and fewer side-effects for the treatment of
      cancers. Among the various TCMs, the root of Scutellaria baicalensis exerts anti
      inflammatory properties as a well-known herb in traditional Chinese medicine.
      Baicalein (5,6,7-trihydroxyflavone) derived from the root of Scutellaria
      baicalensis is a bioactive compound, which possesses a powerful pro-apoptotic
      activity in various cancers such as hepatocellular carcinoma and myeloma.
      However, the effects of baicalein on ES cells remain still unknown. We
      anticipated that baicalein also has apoptotic activity in ES. The aim of the
      present study was to investigate the effects of baicalein on viability,
      apoptosis, migration and invasion of ES cells, and further to elaborate the
      molecular mechanism of baicalein-induced ES cell apoptosis. We found that
      baicalein markedly inhibited ES cells viability in a time- and dose-dependent
      manner, especially SK-ES-1 cells and could promote the apoptosis of ES cells.
      Additionally, baicalein was capable of upregulating the expression of the pro
      apoptotic proteins Bax and cytochrome c, reducing the expression of the anti
      apoptotic protein Bcl-2, elevating the ratio of Bax/Bcl-2, and triggering the
      mitochondrial apoptotic pathway, which led to caspase-3 and caspase-9 activation
      and PARP cleavage. Meanwhile, the activation of caspase-8 and the death receptor
      pathway was also observed. Besides, baicalein could reduce ES migration and
      invasion in vitro, which showed its potential to inhibit ES metastasis, besides
      contributing to the decrease in the expression of matrix metalloproteinases (MMP)
      2 and MMP-9. In conclusion, baicalein has a potent tumor-suppressor activity by
      inducing cell apoptosis through the mitochondrial apoptotic pathway and the death
      receptor pathway in ES cells, thus it may serve as a novel and effective
      candidate agent for ES treatment.

PMID- 29039471
TI  - Hydrogen sulfide alleviates myocardial fibrosis in mice with alcoholic
      cardiomyopathy by downregulating autophagy.
AB  - Myocardial fibrosis is one of the most important pathological features of
      alcoholic cardiomyopathy (ACM). Hydrogen sulfide (H2S) exerts protective effects
      in various types of cardiovascular disease, which has been demonstrated by many
      previous studies. However, there is a lack of adequate research on the effect of
      H2S on myocardial fibrosis in ACM. The present study aimed to investigate the
      etiopathogenic role of H2S in myocardial fibrosis induced by chronic alcohol
      intake. An ACM mouse model was induced by consumption of 4% ethanol solution in
      drinking water for 12 weeks. Sodium hydrosulfide (NaHS) was used as a donor to
      provide exogenous H2S. Twelve weeks later, mice were sacrificed to calculate the
      heart to body weight ratio. The degree of myocardial collagen deposition was
      evaluated by Masson's and Van Gieson's staining, the expression level of collagen
      I was measured by immunohistochemistry and autophagosomes were observed by
      transmission electron microscopy. In addition, the expression levels of autophagy
      associated proteins and fibrosis-associated proteins were detected by western
      blotting, and the expression levels of miR-21 and miR-211 were detected by
      reverse transcription-quantitative polymerase chain reaction. The outcomes of the
      study revealed that chronic alcohol intake results in myocardial fibrosis,
      enhanced myocardial collagen deposition and increased expression levels of
      collagen I, autophagy, autophagy-associated proteins (Beclin 1, Atg3 and Atg7)
      and fibrosis-associated proteins (MMP8, MMP13, MMP14, MMP17 and TGF-beta1), as
      well as miR-21 and miR-221. These results were markedly reversed following
      treatment with H2S. The present study confirmed that H2S relieves myocardial
      fibrosis in mice with ACM, and the underlying mechanism may involve the
      downregulation of autophagy and miR-21 and miR-211 expression levels.

PMID- 29039472
TI  - E2F1 silencing inhibits migration and invasion of osteosarcoma cells via
      regulating DDR1 expression.
AB  - In the present study, knockdown of E2F1 impaired the migration and invasion of
      osteosarcoma cells. Further analysis showed that E2F1 knockdown decreased the
      expression of discoidin domain receptor 1 (DDR1) which plays a crucial role in
      many fundamental processes such as cell differentiation, adhesion, migration and
      invasion. Luciferase and ChIP assays confirmed that E2F1 silencing attenuated the
      expression of DDR1 through disrupting E2F1-mediated transcription of DDR1 in
      osteosarcoma cells. Similarly with the effect of E2F1 silencing, DDR1 knockdown
      weakened the migratory and invasive capabilities of osteosarcoma cells; while
      overexpression of DDR1 resulted in a significant increase of cell motility and
      invasiveness, even after knocking down E2F1. Interestingly, inactivation of
      E2F1/DDR1 pathway by shRNA weakened STAT3 signaling and subsequently suppressed
      the epithelial-mesenchymal transition (EMT) of osteosarcoma cells, as shown with
      decreased vimentin, MMP2, MMP9, and increased E-cadherin. Consistently, high
      expressions of E2F1 and DDR1 observed in osteosarcoma tissues were related to TNM
      stage and metastasis. In addition, high level of E2F1 or DDR1 was associated with
      poor prognosis in osteosarcoma patients. These results suggest that
      E2F1/DDR1/STAT3 pathway is critical for malignancy of osteosarcoma, which may
      provide a novel prognostic indicator or approach for osteosarcoma therapy.

PMID- 29039473
TI  - Altered expression profiles of circular RNA in colorectal cancer tissues from
      patients with lung metastasis.
AB  - The lung is the most common extra-abdominal site of metastasis in colorectal
      cancer (CRC), in which circular RNA (circRNA) may have a crucial role. Therefore,
      the present study detected circRNA expression to identify novel targets to
      further study lung metastasis in CRC. In the present study, total RNA was
      extracted from CRC tissues of patients with and without lung metastasis to
      perform high-throughput microarray assay in order to detect differentially
      expressed circRNA. Following this, gene ontology (GO) and pathway analyses of the
      genes producing differentially expressed circRNA were performed to predict the
      function of circRNA using standard enrichment computational methods.
      Additionally, the circRNA/microRNA (miRNA) interactions were constructed with
      bioinformatics methods to predict the binding of miRNA with circRNA. In the CRC
      tissues from patients with lung metastasis, 431 circRNA were detected to be
      differentially expressed, including 192 upregulated and 239 downregulated over 2
      fold compared with the CRC tissues without metastasis. Furthermore, GO analysis
      revealed that the genes producing upregulated circRNA were involved in DNA
      repair, while the genes producing downregulated circRNA were enriched in signal
      transduction. By pathway analysis, it was identified that the genes producing
      downregulated circRNA were involved in the nuclear factor-kappaB and Wnt
      signaling pathway in the CRC tissues from patients with lung metastasis compared
      with the CRC tissues without metastasis. In addition, it was demonstrated that
      hsa_circRNA_105055, hsa_circRNA_086376 and hsa_circRNA_102761 could commonly bind
      with miR-7 regulating target genes PRKCB, EPHA3, BRCA1 and ABCC1. The findings of
      the present study may provide a novel perspective on circRNA and lay a foundation
      for future research of potential roles of circRNA in CRC with lung metastasis.

PMID- 29039474
TI  - Evaluation of a radiocobalt-labelled affibody molecule for imaging of human
      epidermal growth factor receptor 3 expression.
AB  - The human epidermal growth factor receptor 3 (HER3) is involved in the
      development of cancer resistance towards tyrosine kinase-targeted therapies.
      Several HER3-targeting therapeutics are currently under clinical evaluation. Non
      invasive imaging of HER3 expression could improve patient management. Affibody
      molecules are small engineered scaffold proteins demonstrating superior
      properties as targeting probes for molecular imaging compared with monoclonal
      antibodies. Feasibility of in vivo HER3 imaging using affibody molecules has been
      previously demonstrated. Preclinical studies have shown that the contrast when
      imaging using anti-HER3 affibody molecules can be improved over time. We aim to
      develop an agent for PET imaging of HER3 expression using the long-lived positron
      emitting radionuclide cobalt-55 (55Co) (T1/2=17.5 h). A long-lived cobalt isotope
      57Co was used as a surrogate for 55Co in this study. The anti-HER3 affibody
      molecule HEHEHE-ZHER3-NOTA was labelled with radiocobalt with high yield, purity
      and stability. Biodistribution of 57Co-HEHEHE-ZHER3-NOTA was measured in mice
      bearing DU145 (prostate carcinoma) and LS174T (colorectal carcinoma) xenografts
      at 3 and 24 h post injection (p.i.). Tumour-to-blood ratios significantly
      increased between 3 and 24 h p.i. (p<0.05). At 24 h p.i., tumour-to-blood ratios
      were 6 for DU145 and 8 for LS174T xenografts, respectively. HER3-expressing
      xenografts were clearly visualized in a preclinical imaging setting already 3 h
      p.i., and contrast further improved at 24 h p.i. In conclusion, the radiocobalt
      labelled anti-HER3 affibody molecule, HEHEHE-ZHER3-NOTA, is a promising tracer
      for imaging of HER3 expression in tumours.

PMID- 29039475
TI  - Transcription factors Nrf2 and NF-kappaB contribute to inflammation and apoptosis
      induced by intestinal ischemia-reperfusion in mice.
AB  - Intestinal ischemia/reperfusion (IIR) is a common pathological event associated
      with intestinal injury and apoptosis with high mortality. Nuclear factor (NF)-E2
      related factor-2 (Nrf2) is a key transcription factor that interacts with NF
      kappaB and has a vital anti-inflammatory effect. However, whether Nrf2 has a role
      in IIR-induced apoptosis and the possible underlining mechanisms, such as
      modulation of the inflammation regulation pathway, have remained to be fully
      elucidated. In the present study, IIR was identified to cause significant
      intestinal injury and apoptosis, with high expression levels of inflammatory
      cytokines, as well as the apoptotic proteins B-cell lymphoma 2 (Bcl-2)-associated
      X protein (Bax) and caspase-3, while simultaneously decreasing the protein levels
      of Bcl-2. The effect was more pronounced after pretreatment of the animals with
      all-trans retinoic acid or brusatol, potent inhibitors of Nrf2. t
      Butylhydroquinone, an Nrf2 activator, significantly attenuated IIR-induced
      intestinal injury and apoptosis, with inhibition of the overexpression of the
      inflammatory cytokines, Bax and caspase-3 protein and partial restoration of Bcl
      2 protein expression. Taken together, these results indicated that increased Nrf2
      expression reduced IIR-induced intestinal apoptosis and that the protective
      function of Nrf2 may be based on its anti-inflammatory effects through the
      inhibition of the NF-kappaB pathway.

PMID- 29039476
TI  - The FNR modules contribute to control nitric oxide synthase catalysis revealed by
      chimera enzymes.
AB  - The reductase domains of neuronal NOS, endothelial NOS and two constitutive
      nitric oxide synthase (cNOS) share higher sequence similarity (>60%). In order to
      evaluate the role of ferredoxin-NADP+ reductase (FNR) module in adjusting NOS
      catalytic activities, chimeras were by interchanging the FNR-like module between
      endothelial NOS and neuronal NOS in the present study. The assays of steady-state
      enzymatic activities for cytochrome c and ferricyanide reduction, NO synthesis
      and NADPH oxidation were performed spectrophotometrically. The two NOS FNR
      modules transferred their ferricyanide reductase character to the chimera
      enzymes. Results showed that the FNR module was important in adjusting electrons
      flow through the reductase domain and out of the FMN module. Results indicated
      that the FNR module was critical in controlling the electron transfer capacities
      of the FMN module.

PMID- 29039477
TI  - Comprehensive analysis of circRNA expression profiles in humans by RAISE.
AB  - Circular RNAs (circRNAs) are pervasively expressed circles of non-coding RNAs.
      Even though many circRNAs have been reported in humans, their expression patterns
      and functions remain poorly understood. In this study, we employed a pipeline
      named RAISE to detect circRNAs in RNA-seq data. RAISE can fully characterize
      circRNA structure and abundance. We evaluated inter-individual variations in
      circRNA expression in humans by applying this pipeline to numerous non-poly(A)
      selected RNA-seq data. We identified 59,128 circRNA candidates in 61 human liver
      samples, with almost no overlap in the circRNA of the recruited samples.
      Approximately 89% of the circRNAs were detected in one or two samples. In
      comparison, 10% of the linear mRNAs and non-coding RNAs were detected in each
      sample. We estimated the variation in other tissues, especially the circRNA high
      abundance tissues, in advance. Only 0.5% of the 50,631 brain circRNA candidates
      were shared among the 30 recruited brain samples, which is similar to the
      proportion in liver. Moreover, we found inter- and intra-individual diversity in
      circRNAs expression in the granulocyte RNA-seq data from seven individuals
      sampled 3 times at one-month intervals. Our findings suggest that careful
      consideration of inter-individual diversity is required when extensively
      identifying human circRNAs or proposing their use as potential biomarkers and
      therapeutic targets in disease.

PMID- 29039478
TI  - Phosphorylation of eIF2alpha suppresses cisplatin-induced p53 activation and
      apoptosis by attenuating oxidative stress via ATF4-mediated HO-1 expression in
      human renal proximal tubular cells.
AB  - Cisplatin is one of the most widely used chemotherapeutic agents for the
      treatment of human cancers. However, the nephrotoxicity of cisplatin limits its
      use as a therapeutic agent. It has been suggested that oxidative stress and p53
      activation play important roles in cisplatin-induced nephrotoxicity. It has been
      demonstrated that the eukaryotic translation initiation factor 2alpha (eIF2alpha)
      may protect HK-2 human renal proximal tubular cells against cisplatin-induced
      apoptosis through inhibition of reactive oxygen species (ROS)-mediated p53
      activation. The aim of the present study was to investigate the effects of siRNA
      mediated knockdown of the PKR-like endoplasmic reticulum kinase (PERK) gene,
      which induces the phosphorylation of eIF2alpha, or Sal003, a selective inhibitor
      of eIF2alpha dephosphorylation, on cisplatin-induced apoptosis in HK-2 cells.
      Cisplatin induced eIF2alpha phosphorylation as well as p53 activation. In
      particular, inhibition of p53 by pifithrin-alpha, and upregulation of eIF2alpha
      phosphorylation by Sal003, reduced cisplatin-induced apoptosis. Of note, Sal003
      mediated upregulation of eIF2alpha phosphorylation suppressed cisplatin-induced
      p53 activation. Furthermore, reduction of eIF2alpha phosphorylation by PERK
      knockdown enhanced cisplatin-induced p53 activation and apoptosis. In addition,
      the ROS scavenger N-acetyl-L-cysteine inhibited eIF2alpha phosphorylation as well
      as p53 activation in HK-2 cells treated with cisplatin, suggesting that oxidative
      stress induced by cisplatin may lead to apoptosis through p53 activation;
      furthermore, this stress may confer resistance to apoptosis via eIF2alpha
      phosphorylation, which was further supported by the finding that cisplatin
      induced ROS generation was attenuated by Sal003, whereas it was enhanced by PERK
      knockdown. Furthermore, cisplatin induced the expression of activating
      transcription factor 4 (ATF4) and heme oxygenase-1 (HO-1) that were enhanced by
      Sal003 and reduced by PERK knockdown. Taken together, these results suggest that
      phosphorylation of eIF2alpha suppresses cisplatin-induced p53 activation and
      apoptosis by attenuating oxidative stress via ATF4-mediated HO-1 expression in HK
      2 cells, as ATF4 expression is usually dependent on the phosphorylation of
      eIF2alpha and may also transcriptionally induce the expression of HO-1 in
      response to oxidative stress. Therefore, regulation of eIF2alpha phosphorylation
      may play an important role in alleviating cisplatin-induced nephrotoxicity.

PMID- 29039479
TI  - Mdig suppresses epithelial-mesenchymal transition and inhibits the invasion and
      metastasis of non-small cell lung cancer via regulating GSK-3beta/beta-catenin
      signaling.
AB  - Mineral dust-induced gene (mdig) can inhibit the invasion and metastasis of A549
      cells. The main purpose of this study was to explore the molecular mechanism
      underlying the inhibitory effect of mdig on cell invasion and metastasis. Mdig
      knockdown and mdig-overexpressing A549 cells and an mdig-overexpressing human
      umbilical vein endothelial cell (HUVEC) line were constructed using lentiviral
      vectors, and western blot analysis was performed to verify the silencing and
      overexpression of the mdig protein. A Transwell invasion assay was used to detect
      the invasive abilities of each experimental group, and Transwell migration and
      scratch assays were used to detect cell migration ability. Western blotting was
      subsequently conducted to detect the major biochemical indices of the GSK
      3beta/beta-catenin pathway and the protein expression levels and modifications of
      epithelial-mesenchymal transition (EMT) transcription factors, as well as changes
      in the expression levels of EMT molecular markers and intercellular adhesion
      proteins. The results indicated that overexpression of mdig in A549 cells
      inhibited cell invasion and metastasis, while silencing of mdig increased the
      invasive and metastatic properties of cells. The molecular mechanism underlying
      the effects of mdig downregulation on A549 cell invasion and metastasis was found
      to involve the inhibition of GSK-3beta phosphorylation, which in turn promoted
      the phosphorylation and destabilization of beta-catenin. This was associated with
      downregulation of the downstream transcription factors slug, snail and ZEB1, thus
      leading to increased expression levels of epithelial cell markers and
      upregulation of the intercellular adhesion molecules E-cadherin, claudin-1, ZO-1,
      integrin beta1 and integrin beta4, which was accompanied by downregulation of the
      mesenchymal cell markers vimentin and N-cadherin. The HUVECs were used to
      validate the aforementioned molecular mechanisms and the same conclusions were
      obtained. The present results indicate that mdig can inhibit the phosphorylation
      of GSK-3beta and promote the phosphorylation and destabilization of beta-catenin,
      in order to suppress the expression of slug, snail, and ZEB1 and the occurrence
      of EMT, and thereby inhibit the invasion and metastasis of non-small cell lung
      cancer (NSCLC).

PMID- 29039480
TI  - MicroRNA-20b promotes cell proliferation via targeting of TGF-beta receptor II
      and upregulates MYC expression in Ewing's sarcoma cells.
AB  - Transforming growth factor-beta receptor II (TGFBR2) is implicated in various
      types of cancer. Most molecules involved in the TGF-beta pathway can be degraded
      by one or more microRNAs (miRNAs). In the present study, we show that miRNA plays
      an important role in downregulating TGFBR2 expression in Ewing's sarcoma (ES)
      cells. Microarray-based analyses revealed that the expression of miR-20b was
      significantly increased, whereas TGFBR2 and MYC were significantly downregulated
      and upregulated, respectively, in all ES cells compared to their expression in
      human mesenchymal stem cells (hMSCs). In ES cell lines, anti-miR-20b increased
      TGFBR2 expression and significantly decreased MYC expression, showing an inverse
      relationship with TGFBR2. The induction by anti-miR-20b further prohibited ES
      cell growth and cell cycle progression. Moreover, decreased miR-20b in ES cells
      significantly inhibited tumor growth in vivo. Taken together, these results
      suggest that miR-20b behaves as an oncogene in ES when its overexpression is
      unregulated by targeting TGFBR2. Because downstream TGFBR2 and TGF-beta signaling
      regulate cell cycle, apoptosis, and tumor proliferation via MYC, our findings may
      contribute to new targeted therapies for ES.

PMID- 29039481
TI  - Administration of erythropoietin prevents bone loss in osteonecrosis of the
      femoral head in mice.
AB  - Long-term administration of glucocorticoid hormones is considered one of
      predominant pathological factors inducing osteonecrosis of the femoral head
      (ONFH) development and progression, in which reduction of blood supply leads to a
      progressive bone loss and impairment of bone structure in the majority of cases.
      In a non-hematopoietic system, erythropoietin (EPO) can stimulate angiogenesis
      and bone regeneration. However, the specific mechanism underlying the role of EPO
      in ONFH remains to be elucidated. Therefore, the purpose of this study was to
      determine the effect of EPO on the prevention of bone loss in ONFH. Male C57BL/6J
      mice 3 months old were divided into two groups: EPO group and control groups.
      ONFH was established by the administration prednisolone (PDS, 100 mg/kg) with co
      treatment of lipopolysaccharide (LPS, 1 mg/kg). ONFH mice received recombinant
      mouse EPO (500 U/kg/day) or saline intramuscularly. The mice were sacrificed at
      2, 4, 6 and 8 weeks following the initiation of treatment. Alterations in the
      general architecture and histomorphology of the right femoral head were
      determined by hematoxylin and eosin staining and micro computed tomography (micro
      CT). The expression of runt-related transcription factor 2 (Runx2), osteocalcin,
      vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion
      molecule (CD31) in the femoral head was tested by immunohistochemistry. Terminal
      deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) assay was
      performed to detect apoptosis in femoral heads. Micro-CT data revealed that EPO
      significantly improved bone volume/total volume and bone mineral density
      following 6 and 8 weeks of treatment. Histological analysis further demonstrated
      that EPO treatment improved the arrangement of trabeculae, thinning of trabeculae
      and other fractures in femoral heads, especially following 6 and 8 weeks of
      treatment. Immunohistochemical analysis suggested that EPO treatment up-regulated
      the expressions of Runx2, osteocalcin, VEGF and CD31 at 4 and 8 weeks. The TUNEL
      apoptosis assay suggested that EPO intervention reduced apoptosis in avascular
      ONFH. Therefore, EPO prevents bone loss in ONFH in mice through enhancing Runx2
      mediated osteogenesis, VEGF-mediated angiogenesis and inhibition of cell
      apoptosis.

PMID- 29039482
TI  - Protective effects of compounds from Garcinia mangostana L. (mangosteen) against
      UVB damage in HaCaT cells and hairless mice.
AB  - Ultraviolet B (UVB) radiation causes alterations in the skin, such as epidermal
      thickening, wrinkle formation and inflammation. Therefore, preventing UVB-induced
      skin damage can promote general health among the human population. Garcinia
      mangostana L. (mangosteen) is a fruit that has become a popular botanical dietary
      supplement because of its perceived role in promoting overall health. The present
      study investigated the photoprotective effects of alpha-, beta-, gamma-mangostins
      and gartanin against UVB radiation using the HaCaT immortalized human
      keratinocyte cell line as an in vitro model and hairless mice as an in vivo
      model. UVB radiation increased the expression of matrix metalloproteinase (MMP)-1
      and -9 and decreased the mRNA expression levels of involucrin, filaggrin and
      loricrin in HaCaT cells; however, these changes were attenuated by pretreating
      the cells with alpha-, beta-, gamma-mangostins and gartanin. Among these
      compounds, alpha-mangostin exhibited the greatest effects in reducing UVB-induced
      skin wrinkles, inhibited epidermal thickening in hairless mice in vivo. Exposure
      to UVB radiation increased the expression of MMPs and pro-inflammatory cytokines
      and activated mitogen-activated protein kinases in hairless mice, but these
      changes were attenuated by alpha-mangostin. The authors suggested that alpha
      mangostin exerts anti-wrinkle and anti-aging properties.

PMID- 29039483
TI  - Dihydromyricetin protects against lipopolysaccharide-induced cardiomyocyte injury
      through the toll-like receptor-4/nuclear factor-kappaB pathway.
AB  - Dihydromyricetin (DHM) is a bioactive flavonoid compound extracted from the stems
      and leaves of Ampelopsis grossedentata. Previous studies have indicated that DHM
      has antioxidation and antitumor capabilities, while the effect of DHM on
      lipopolysaccharide (LPS)-induced cardiomyocyte injury has not been clarified.
      Therefore, the aim of the present study was to investigate the effect of DHM on
      LPS-induced cardiomyocyte injury. In the present study, cardiomyocytes were
      randomized to the control (PBS), LPS and DHM + LPS groups. The LPS group was
      treated with 10 ug/ml LPS for 12 h and the DHM + LPS group was treated with 100
      or 25 uM DHM 12 h prior to treatment with LPS. The protective effect of DHM on
      LPS-induced cardiomyocytes injury was evaluated by Cell Counting kit-8 assay,
      TUNEL staining, reverse transcription-quantitative polymerase chain reaction and
      western blot analysis. The results demonstrated that LPS treatment led to
      cardiomyocyte apoptosis, and these effects were significantly attenuated by DHM.
      Furthermore, LPS treatment downregulated the expression of B-cell lymphoma 2
      apoptosis regulator (Bcl-2) and induced increased expression of Bcl-2-associated
      X apoptosis regulator (Bax). Additionally, DHM treatment reversed LPS-induced
      changes in Bcl-2 expression and Bax expression in cardiomyocytes, and rescued
      cells from apoptosis. In addition, increased mRNA expression levels of tumor
      necrosis factor-alpha and interleukin-6 induced by LPS were attenuated following
      treatment with DHM. Further investigation demonstrated that DHM suppressed the
      activation of toll-like receptor-4 (TLR4), which is involved in regulating the
      downstream signaling pathway of nuclear factor-kappaB (NF-kappaB). DHM attenuated
      LPS-induced cardiomyocyte injury, the potential mechanism responsible for this
      effect may involve inhibition of TLR4 activation and subsequent regulation of the
      associated downstream signaling pathway of NF-kappaB. The current study indicates
      that DHM may protect cardiomyocytes against LPS-induced injury by inhibition of
      the TLR4/NF-kappaB signaling pathway. The results of the present study may
      provide support for the development DHM as a strategy for the treatment of heart
      failure in septic shock.

PMID- 29039484
TI  - miR-203 contributes to IL-17-induced VEGF secretion by targeting SOCS3 in
      keratinocytes.
AB  - Interleukin (IL)-17 signaling serves an important role in the development and
      pathogenesis of psoriasis; a chronic skin disease characterized by increased
      dermal vascularity and the hyperproliferation of keratinocytes. microRNA (miR)
      203 is preferentially expressed in the skin and is an important regulator of
      keratinocyte differentiation. miR-203 has been implicated in a number of skin
      diseases, including psoriasis. However, the role of miR-203 in IL-17-induced
      vascular endothelial growth factor (VEGF) secretion has yet to be elucidated. The
      present study demonstrated that miR-203 expression was upregulated in the ears of
      IL-17-stimulated mice and IL-17-treated HaCaT cells. In addition, the IL-17
      induced increase in miR-203 expression activated the Janus kinase/signal
      transducer and activator of transcription signaling pathway and promoted VEGF
      secretion in HaCaT cells. Furthermore, miR-203 was observed to bind to the 3'
      untranslated region of suppressor of cytokine signaling 3 (SOCS3) and inhibited
      SOCS3 expression. The results suggest that miR-203 expression may be upregulated
      by IL-17 stimulation, and miR-203 is a positive regulator of IL-17-induced VEGF
      secretion. The present study may support potential therapeutic strategies for the
      treatment of psoriasis.

PMID- 29039485
TI  - Calcium dobesilate may alleviate diabetes-induced endothelial dysfunction and
      inflammation.
AB  - Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease.
      However, the pathogenesis of DKD remains unclear, and no effective treatments for
      the disease are available. Thus, there is an urgent need to elucidate the
      pathogenic mechanisms of DKD and to develop more effective therapies for this
      disease. Human umbilical vein endothelial cells (HUVECs) were cultured using
      different D-glucose concentrations to determine the effect of high glucose (HG)
      on the cells. Alternatively, HUVECs were incubated with 100 umol/l calcium
      dobesilate (CaD) to detect its effects. The authors subsequently measured HUVEC
      proliferation via cell counting kit-8 assays. In addition, HUVEC angiogenesis was
      investigated via migration assays and fluorescein isothiocyanate (FITC)-labelled
      bovine serum albumin (BSA) permeability assays. The content or distribution of
      markers of endothelial dysfunction [vascular endothelial growth factor (VEGF),
      VEGF receptor (R) and endocan) or inflammation [intercellular adhesion molecule
      (ICAM)-1, monocyte chemotactic protein (MCP)-1 and pentraxin-related protein
      (PTX3)] was evaluated via reverse transcription-quantitative polymerase chain
      reaction and western blotting. HG treatment induced increased in VEGF, VEGFR,
      endocan, ICAM-1, MCP-1 and PTX3 mRNA and protein expression in HUVECs. HG
      treatment for 24 to 48 h increased cell proliferation in a time-dependent manner,
      but the cell proliferation rate was decreased at 72 h of HG treatment.
      Conversely, CaD inhibited abnormal cell proliferation. HG treatment also
      significantly enhanced HVUEC migration compared to the control treatment. In
      contrast, CaD treatment partially inhibited HUVEC migration compared to HG
      exposure. HG-treated HUVECs exhibited increased FITC-BSA permeability compared to
      control cells cultured in medium alone; however, CaD application prevented the HG
      induced increase in FITC-BSA permeability and suppressed HG-induced
      overexpression of endothelial markers (VEGF, VEGFR-2, endocan) and inflammation
      markers (ICAM-1, MCP-1, PTX3) in HUVECs. CaD has angioprotective properties and
      protects endothelial cells partly by ameliorating HG-induced inflammation. The
      current results demonstrated the potential applicability of CaD to the treatment
      of diabetic nephropathy, particularly during the early stages of this disease.

PMID- 29039487
TI  - Functional analysis of HOXA10 and HOXB4 in human medulloblastoma cell lines.
AB  - Medulloblastoma (MB) is a malignant childhood brain tumor which at molecular
      level is classified into at least four major subtypes: WNT, SHH, group C and
      group D differing in response to treatment. Previous studies have associated
      changes in expression levels and activation of certain HOX genes with MB
      development. In the present study, we investigate the role of HOX genes in two
      attributes acquired by tumor cells: migration and proliferation potential, as
      well as, in vivo tumorigenic potential. We analyzed UW402, UW473, DAOY and ONS-76
      human pediatric MB cell lines and cerebellum primary cultures. Two-color
      microarray-based gene expression analysis was used to identify differentially
      expressed HOX genes. Among the various HOX genes significantly overexpressed in
      DAOY and ONS-76 cell lines compared to UW402 and UW473 cell lines, HOXA10 and
      HOXB4 were selected for further analysis. The expression levels of these HOX
      genes were validated by real-time PCR. A mouse model was used to study the effect
      of the HOXA10 and HOXB4 genes on the in vivo tumorigenic potential and the in
      vitro proliferative and migration potential of MB cell lines. Our results show
      that the inhibition of HOXA10 in DAOY cell line led to increased in vitro cell
      migration while in vitro cell proliferation or in vivo tumorigenic potential were
      unaffected. We also observed that induced expression of HOXB4 in the UW473 cell
      line significantly reduced in vitro cell proliferation and migration capability
      of UW473 cells with no effect on the in vivo tumorigenicity. This suggests that
      HOXA10 plays a role in migration events and the HOXB4 gene is involved in
      proliferation and migration processes of medulloblastoma cells, however, it
      appears that these genes are not essential for the tumorigenic process of these
      cells.

PMID- 29039486
TI  - Analysis of miRNA expression profiling in human umbilical vein endothelial cells
      affected by heat stress.
AB  - To investigate the regulation of endothelial cell (EC) microRNAs (miRNAs) altered
      by heat stress, miRNA microarrays and bioinformatics methods were used to
      determine changes in miRNA profiles and the pathophysiological characteristics of
      differentially expressed miRNAs. A total of 31 differentially expressed miRNAs
      were identified, including 20 downregulated and 11 upregulated miRNAs. Gene
      Ontology (GO) enrichment analysis revealed that the validated targets of the
      differentially expressed miRNAs were significantly enriched in gene transcription
      regulation. The pathways were also significantly enriched in the Kyoto
      Encyclopedia of Genes and Genomes analysis, and most were cancer-related,
      including the mitogen-activated protein kinase signaling pathway, pathways
      involved in cancer, the Wnt signaling pathway, the Hippo signaling pathway,
      proteoglycans involved in cancer and axon guidance. The miRNA-gene and miRNA-GO
      network analyses revealed several hub miRNAs, genes and functions. Notably, miR
      3613-3p played a dominant role in both networks. MAP3K2, MGAT4A, TGFBR1, UBE2R2
      and SMAD4 were most likely to be controlled by the altered miRNAs in the miRNA
      gene network. The miRNA-GO network analysis revealed significantly complicated
      associations between miRNAs and different functions, and that the significantly
      enriched functions targeted by the differentially expressed miRNAs were mostly
      involved in regulating gene transcription. The present study demonstrated that
      miRNAs are involved in the pathophysiology of heat-treated ECs. Understanding the
      functions of miRNAs may provide novel insights into the molecular mechanisms
      underlying the heat-induced pathophysiology of ECs.

PMID- 29039488
TI  - MicroRNA-454 inhibits tumor cell proliferation, migration and invasion by
      downregulating zinc finger E-box-binding homeobox 1 in gastric cancer.
AB  - Gastric cancer is the fourth most common malignancy and the third leading cause
      of cancer-associated mortality globally. Accumulating studies have identified the
      involvement of microRNAs in the initiation and progression of gastric cancer.
      This study was aimed to investigate the expression, functional roles of microRNA
      454 (miR-454) and its direct target gene in gastric cancer. According to the
      results, the expression level of miR-454 was demonstrated to be reduced in
      gastric cancer tissues and cell lines compared with corresponding distant non
      tumor gastric tissues and human immortalized gastric epithelial, respectively.
      miR-454 mimic transfection led to inhibition of gastric cancer cells
      proliferation, migration and invasion in vitro. Bioinformatic analysis predicated
      that zinc finger E-box-binding homeobox 1 (ZEB1) is a potential target gene of
      miR-454. Luciferase reporter assays revealed that miR-454 directly targeted the
      3'UTR of ZEB1. miR-454 overexpression significantly decreased the ZEB1 mRNA and
      protein expression levels. ZEB1 knockdown could mimic the tumor suppressive roles
      induced by miR-454 overexpression on gastric cancer cell proliferation, migration
      and invasion. In conclusion, the present study suggested that miR-454 under
      expression may be involved in gastric cancer initiation and progression, by
      promoting proliferation, migration and invasion by directly targeting ZEB1. miR
      454/ZEB1-based targeted therapy may be a potential strategy for the treatment of
      gastric cancer.

PMID- 29039489
TI  - ID1 contributes to cell growth invasion and migration in salivary adenoid cystic
      carcinoma.
AB  - Previous studies have reported that inhibitor of DNA binding 1 (ID1) exerts an
      oncogenic role in a number of tumors. In the present study, the role of ID1 in
      the growth, invasion and migration of salivary adenoid cystic carcinoma (SACC)
      cells was investigated. ID1 expression in clinical SACC samples was compared with
      that in normal salivary tissues using immunohistochemical staining, and the
      correlation between ID1 expression and clinical pathological characteristics was
      then determined. Subsequently, ID1 was overexpressed or silenced to investigate
      the effects of ID1 expression on SACC cell proliferation, invasion and migration.
      In addition, the gene expression levels of known ID1 target genes, including
      S100A9, CDKN2A and matrix metalloproteinase 1 (MMP1) was measured using reverse
      transcription-quantitative polymerase chain reaction to elucidate the potential
      mechanisms of ID1 in SACC. The results of the present study indicated that the
      protein expression levels of ID1 were significantly increased in the SACC tissues
      compared with that in the normal salivary tissues (P<0.001), and a positive
      correlation between ID1 expression and tumor stage (P=0.001), tumor invasion
      (P=0.002) and metastasis (P=0.019) in SACC was observed. Knockdown of ID1 in SACC
      cells significantly inhibited cell growth, invasion and migration (all P<0.01),
      whereas overexpression of ID1 promoted cell proliferation, invasion and migration
      (all P<0.01). The gene expression level of MMP1 was significantly reduced
      following ID1 knockdown in SACC-83 cells when compared with negative controls
      (P<0.05), whereas S100A9 and CDKN2A expression levels were significantly
      upregulated (both P<0.05). The results suggest that ID1 may regulate the growth,
      invasion and migration of SACC cells, and that MMP1, S100A9 and CDKN2A may serve
      as target genes of ID1 and mediate the effects of ID1 in SACC cells. Therefore,
      ID1 may present a potential target gene for the treatment of patients with SACC
      to inhibit cancer cell growth and metastasis.

PMID- 29039490
TI  - IL-8 promotes proliferation and inhibition of apoptosis via STAT3/AKT/NF-kappaB
      pathway in prostate cancer.
AB  - Interleukin-8 (IL-8) possesses tumorigenic and proangiogenic properties, and is
      overexpressed in many human cancer types. However, only few studies have
      demonstrated the mechanisms of action of IL-8 regarding the ability to promote
      proliferation and to inhibit apoptosis in prostate cancer. Here, the aim of the
      present study was to investigate the effects of IL-8 on the prostate cancer cell
      line and determine possible mechanisms underlying its effect. In this study, IL-8
      was shown to be significantly upregulated in prostate cancer compared with paired
      normal control tissues. The data showed that IL-8 exhibits direct oncogenicity,
      which significantly induced cell proliferation, invasion and attenuated apoptosis
      in prostate cancer cells via signal transducer and activator of transcription
      3/protein kinase B/nuclear factor-kappaB signaling pathways. In conclusion,
      modulation of IL-8 expression or its associated signaling pathway may provide a
      novel working mechanism of IL-8 in prostate cancer, and a promising strategy for
      controlling the progression and metastasis of prostate cancer.

PMID- 29039491
TI  - Non-canonical Hedgehog signaling activation in ovarian borderline tumors and
      ovarian carcinomas.
AB  - Hedgehog signaling pathway has been implicated in the pathology of ovarian
      cancer, and Survivin (BIRC5) has been suggested as a novel target of this
      pathway. Herein we investigated the role of Hedgehog signaling pathway and
      Survivin in ovarian carcinoma and borderline tumor samples. We aimed to determine
      possible ways of pathway modulation on primary ovarian cancer cells and an
      established cell line. RNA was extracted from fresh tumors and control tissues
      and gene expression was examined using qRT-PCR. Pathway activity in cell lines
      was examined after treatment with cyclopamine, SHH protein, GANT-61 or lithium
      chloride using qRT-PCR, western blot and confocal microscopy. The difference
      between control tissue, borderline tumors and carcinomas can be seen in GLI1 and
      SUFU gene expression, which is significantly higher in borderline tumors compared
      to carcinomas. SUFU also shows lower expression levels in higher FIGO stages
      relative to lower stages. BIRC5 is expressed in all tumors and in healthy ovarian
      tissues compared to our control tissue, healthy fallopian tube samples. Primary
      cells developed from ovarian carcinoma tissue respond to cyclopamine treatment
      with a short-term decrease in cell proliferation, downregulation of Hedgehog
      pathway genes, including BIRC5, and changes in protein dynamics. Stimulation with
      SHH protein results in increased cell migration, while GLI1 transfection or PTCH1
      silencing demonstrate pathway upregulation. The pathway activity can be modulated
      by LiCl at the GSK3beta-SUFU-GLI level, suggesting at least partial non-canonical
      activation. Downregulation of the pathway with GANT-61 has proved to be more
      effective than cyclopamine. GLI inhibitors may be a superior treatment option in
      ovarian cancer compared to SMO inhibitors.

PMID- 29039492
TI  - Black rice-derived anthocyanins inhibit HER-2-positive breast cancer epithelial
      mesenchymal transition-mediated metastasis in vitro by suppressing FAK signaling.
AB  - This study aimed to investigate the role of focal adhesion kinase (FAK) signaling
      in the inhibitory effects of black rice anthocyanins (BRACs) on human epidermal
      growth factor receptor-2 (HER-2)-positive human breast cancer cell metastasis,
      using the MCF-10A, MCF-7 and MDA-MB-453 cells. BRACs exerted an anti-metastatic
      effect on the HER-2-positive breast cancer cells. The effects of BRACs on the
      proliferation of the MDA-MB-453 cells were examined by cell counting kit-8 assay.
      A wound-healing assay was used to examine the effects of BRACs on the migration
      of the breast cancer cells. BRACs interrupted migration and invasion. BRACs
      decreased the migration distance of the HER-2-positive human breast cancer cells,
      MDA-MB-453, by 37% compared with the cells in the untreated group. They also
      reduced the number of invading MDA-MB-453 cells by 68%. In addition, BRACs
      exerted an inhibitory effect on epithelial-mesenchymal transition. Western blot
      analysis revealed that BRACs decreased the phosphorylation of FAK, cSrc and
      p130Cas. The FAK inhibitor, Y15, was also used to further evaluate the role of
      FAK signaling in the anti-metastatic effects of BRACs on MDA-MB-453 cells. The
      results of western blot analysis revealed that BRACs increased the expression of
      the epithelial marker, E-cadherin, and decreased the expression of the
      mesenchymal markers, fibronectin and vimentin, in the MDA-MB-453 cells. In
      addition, BRACs decreased the interaction between HER-2 and FAK, FAK and cSrc,
      cSrc and p130Cas, and between FAK and p130Cas. These results suggest that BRACs
      suppress the metastasis of HER-2-positive breast cancer in vitro, and that the
      cSrc/FAK/p130Cas pathway plays a vital role in this inhibitory effect.

PMID- 29039493
TI  - Actein induces apoptosis in leukemia cells through suppressing RhoA/ROCK1
      signaling pathway.
AB  - Actein is a tetracyclic triterpenoid compound, extracted from the rhizome of
      Cimicifuga foetida, exhibiting anticancer activities as previously reported.
      However, the effects of actein on human leukemia have not been explored before.
      In this study, the role of actein in regulating apoptosis induction in human
      leukemia cells was investigated. Actein administration significantly enhanced
      apoptosis, especially in human leukemia cell line of U937 and the primary human
      leukemia cells. The promotion was accompanied by caspase-9, caspase-3 and
      poly(ADP-ribose) polymerase (PARP) cleavage, and cytochrome c (Cyto-c) release.
      Additionally, translocation of Bax into mitochondria was increased by actein,
      while anti-apoptotic signals of myeloid cell leukemia-1 (Mcl-1) and B cell
      CLL/lymphoma 2 (Bcl-2) were decreased, accompanied by reduced phosphorylated Bcl
      2-associated death promoter (Bad). Furthermore, protein kinase B (AKT) activation
      was downregulated by actein treatment in U937 cells. RhoA, but not caspase-3,
      regulated Rho kinase 1 (ROCK1) expression induced by actein. Suppression of RhoA
      and ROCK1 reduced ROCK1 expression, caspase-9, caspase-3 and PARP cleavage. In
      contrast, AKT inactivity enhanced apoptosis levels, as well as caspase signaling
      pathway expression. The anticancer role of actein was potentiated by inactivating
      AKT. In vivo, U937-bearing tumor growth was suppressed by actein, which was
      related to ROCK1 suppression, AKT dephosphorylation and apoptosis induction.
      These results indicated that actein has a suppressive role in human leukemia
      progression through inactivating RhoA/ROCK1 and inducing caspases.

PMID- 29039494
TI  - Internal driving factors leading to extrahepatic manifestation of the hepatitis C
      virus infection.
AB  - The hepatitis C virus (HCV) infection is associated with various extrahepatic
      manifestations, which are correlated with poor outcomes, and thus increase the
      morbidity and mortality of chronic hepatitis C (CHC). Therefore, understanding
      the internal linkages between systemic manifestations and HCV infection is
      helpful for treatment of CHC. Yet, the mechanism by which the virus evokes the
      systemic diseases remains to be elucidated. In the present study, using gene set
      enrichment analysis (GSEA) and signaling pathway impact analysis (SPIA), a
      comprehensive analysis of microarray data of mRNAs was conducted in HCV-infected
      and -uninfected Huh7.5 cells, and signaling pathways (which are significantly
      activated or inhibited) and certain molecules (which are commonly important in
      those signaling pathways) were selected. Forty signaling pathways were selected
      using GSEA, and eight signaling pathways were selected with SPIA. These pathways
      are associated with cancer, metabolism, environmental information processing and
      organismal systems, which provide important information for further clarifying
      the intrinsic associations between syndromes of HCV infection, of which seven
      pathways were not previously reported, including basal transcription factors,
      pathogenic Escherichia coli infection, shigellosis, gastric acid secretion, dorso
      ventral axis formation, amoebiasis and cholinergic synapse. Ten genes, SOS1,
      RAF1, IFNA2, IFNG, MTHFR, IGF1, CALM3, UBE2B, TP53 and BMP7 whose expression may
      be the key internal driving molecules, were selected using the online tool Anni
      2.1. Furthermore, the present study demonstrated the internal linkages between
      systemic manifestations and HCV infection, and presented the potential molecules
      that are key to those linkages.

PMID- 29039495
TI  - Protective effects of neem (Azadirachta indica A. Juss.) leaf extract against
      cigarette smoke- and lipopolysaccharide-induced pulmonary inflammation.
AB  - Neem (Azadirachta indica A. Juss.) leaf has been reported to exert anti
      inflammatory, antibacterial and antioxidant effects. The purpose of this study
      was to investigate the protective effects of neem leaf extract (NLE) against
      cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced pulmonary
      inflammation. Treatment with NLE significantly attenuated the infiltration of
      inflammatory cells, such as neutrophils and macrophages in bronchoalveolar lavage
      fluid (BALF). NLE also reduced the production of reactive oxygen species and the
      activity of neutrophil elastase in BALF. Moreover, NLE attenuated the release of
      pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and
      interleukin (IL)-6 in BALF. NLE inhibited the recruitment of inflammatory cells
      and the expression of monocyte chemoattractant protein-1 (MCP-1) in the lungs of
      mice with CS- and LPS-induced pulmonary inflammation. NLE also decreased the
      expression of inducible nitric oxide synthase (iNOS) in the lungs of the mice CS-
      and LPS-induced pulmonary inflammation. Furthermore, treatment with NLE
      significantly attenuated the activation of extracellular signal-regulated kinase
      (ERK) and c-Jun N-terminal kinase (JNK) in the lungs mice exposed to CS and LPS.
      NLE also inhibited the phosphorylation of nuclear factor (NF)-kappaB and
      inhibitor of NF-kappaB (IkappaB) in the lungs of mice expose to CS and LPS. These
      findings thus suggest that NLE has potential for use in the treatment of chronic
      obstructive pulmonary disease.

PMID- 29039496
TI  - GSK-3beta inhibitor 6-bromo-indirubin-3'-oxime promotes both adhesive activity
      and drug resistance in colorectal cancer cells.
AB  - Multi-targets inhibitor 6-bromo-indirubin-3'-oxime (BIO) has diverse biological
      effects on cancer cells. The key component of the beta-catenin destruction
      complex glycogen synthase kinase 3beta (GSK-3beta), one of the major target for
      BIO, polyubiquitination and degradation of the main oncoprotein beta-catenin in
      colorectal cancer (CRC). In the present study, we evaluated the effect of BIO on
      drug resistance and biological properties of CRC cells. Whole-genome
      transcriptional profiling revealed that differentially expressed genes were
      mainly centered on well-characterized signaling pathways including stem cell,
      cell adhesion and cell growth in BIO-treated CRC cells. BIO treatment
      downregulated migration and invasion abilities of CRC cells, accompanying with
      MMP-9 downregulated and E-cadherin upregulated CRC cells. BIO treatment decreased
      apoptosis induced by 5-Fu/DDP in CRC SW480 cells. In addition, BIO treatment
      reversed the 5-Fu-induced CD133+ cell downregulation trend in CRC SW620 cells.
      After incubation with BIO, the expression levels of EpCAM, TERT and DCAMKL-1
      proteins were upregulated in CRC cells. BIO treatment downregulated the activity
      of GSK-3beta, upregulated and transported beta-catenin to the nucleus in CRC
      cells. Our findings reveal that BIO treatment upregulated stemness, adhesive and
      chemoresistance of CRC cells. GSK-3beta inhibition and WNT/beta-catenin
      activation by BIO, may partly result in the biological behavior alterations in
      CRC cells.

PMID- 29039497
TI  - Edaravone protects the retina against ischemia/reperfusion-induced oxidative
      injury through the PI3K/Akt/Nrf2 pathway.
AB  - Retinal ischemia/reperfusion (I/R) injury can occur as a result of a number of
      ocular diseases or ischemic events in the brain, leading to possible vision loss
      if not treated properly. The overproduction of reactive oxygen species is
      important in the process of I/R injury. Edaravone, a free radical scavenger, has
      been demonstrated to have a neuroprotective effect in cerebral ischemia; however,
      its effect against retinal I/R injury remains to be fully elucidated. Therefore,
      the present study investigated the effects of edaravone on the oxidative
      parameters, retinal inflammation and apoptosis induced by I/R injury, and treated
      photoreceptor-derived 661W cells with hydrogen peroxide (H2O2) and edaravone to
      examine the underlying mechanism. For the in vivo study, oxidative parameters
      (malondialdehyde, DNA fragmentation, total antioxidant status, superoxide
      dismutase and glutathione) in the retina, retinal thickness, and apoptotic index
      in the ganglionic cell layer and inner nuclear layer were measured. For the in
      vitro study, the effects of edaravone or nuclear factor erythroid-2-related
      factor 2 (Nrf2) small interfering RNA or phosphatidylinositol 3-kinase (PI3K)/Akt
      inhibitors on cell viability, membrane integrity, levels of phosphorylated-Akt,
      Akt and nuclear Nrf2 of H2O2-treated 661W cells were examined. The results
      demonstrated that edaravone inhibited the oxidative injury in the retina induced
      by the retinal I/R procedure and increased retinal inflammation, and apoptosis.
      The results of the in vitro experiments demonstrated that edaravone effectively
      protected the viability and the membrane integrity of the H2O2-treated 661W cells
      via the phosphatidylinositol 3-kinase (PI3K)/Akt/Nrf2pathway. These results
      indicated the potential protective effect of edaravone against retinal I/R injury
      and provided a novel explanation for the protective effects of edaravone.

PMID- 29039498
TI  - Tanshinone IIA inhibits high glucose-induced proliferation, migration and
      vascularization of human retinal endothelial cells.
AB  - Diabetic retinopathy is the most universal and severe complication of diabetes
      mellitus. The primary aim of the present study was to determine whether
      tanshinone IIA (TSA) has an inhibitory effect on the proliferation, migration and
      vascularization of human retinal endothelial cells (HREC) under high glucose (HG)
      conditions and the associated underlying mechanism. It was demonstrated that TSA
      exhibited a significant inhibitory effect on the proliferation, migration and
      vascularization of HRECs in a dose-dependent manner, under conditions of high
      glucose (25 mM) medium. However, there was no distinct inhibitory effect on HREC
      proliferation, migration and vascularization under normal glucose (NG, 5.5 mM
      glucose) conditions. Reverse transcription-quantitative polymerase chain
      reaction, western blotting and immunofluorescence experiments were conducted to
      evaluate the effects of TSA on the expression levels of vascular endothelial
      growth factor (VEGF) and intercellular adhesion molecule (ICAM)-1. It was
      demonstrated that TSA significantly downregulated the expression levels of VEGF
      and ICAM-1 in a dose-dependent manner under HG conditions. Overall, the results
      of the present study indicate that TSA-mediated inhibition of proliferation,
      migration and vascularization in HRECs may be associated with its ability to
      affect the expression levels of VEGF and ICAM-1.

PMID- 29039499
TI  - An investigation of methyl tert-butyl ether-induced cytotoxicity and protein
      profile in Chinese hamster ovary cells.
AB  - Methyl tert-butyl ether (MTBE) is widely used as an oxygenating agent in gasoline
      to reduce harmful emissions. However, previous studies have demonstrated that
      MTBE is a cytotoxic substance that has harmful effects in vivo and in vitro.
      Although remarkable progress has been made in elucidating the mechanisms
      underlying the MTBE-induced reproductive toxicological effect in different cell
      lines, the precise mechanisms remain far from understood. The present study aimed
      to evaluate whether mammalian ovary cells were sensitive to MTBE exposure in
      vitro by assessing cell viability, lactate dehydrogenase (LDH) leakage,
      malondialdehyde (MDA) content and antioxidant enzyme activities. In addition, the
      effect of MTBE exposure on differential protein expression profiles was examined
      by two-dimensional electrophoresis and matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry. MTBE exposure induced
      significant effects on cell viability, LDH leakage, plasma membrane damage and
      the activity of antioxidant enzymes. In the proteomic analysis, 24 proteins were
      demonstrated to be significantly affected by MTBE exposure. Functional analysis
      indicated that these proteins were involved in catalytic activity, binding,
      structural molecule activity, metabolic processes, cellular processes and
      localization, highlighting the fact that the cytotoxic mechanisms resulting from
      MTBE exposure are complex and diverse. The altered expression levels of two
      representative proteins, heat shock protein family A (Hsp70) members 8 and 9,
      were further confirmed by western blot analysis. The results revealed that MTBE
      exposure affects protein expression in Chinese hamster ovary cells and that
      oxidative stress and altered protein levels constitute the mechanisms underlying
      MTBE-induced cytotoxicity. These findings provided novel insights into the
      biochemical mechanisms involved in MTBE-induced cytotoxicity in the reproductive
      system.

PMID- 29039500
TI  - Gene expression profile identifies potential biomarkers for human intervertebral
      disc degeneration.
AB  - The present study aimed to reveal the potential genes associated with the
      pathogenesis of intervertebral disc degeneration (IDD) by analyzing microarray
      data using bioinformatics. Gene expression profiles of two regions of the
      intervertebral disc were compared between patients with IDD and controls.
      GSE70362 containing two groups of gene expression profiles, 16 nucleus pulposus
      (NP) samples from patients with IDD and 8 from controls, and 16 annulus fibrosus
      (AF) samples from patients with IDD and 8 from controls, was downloaded from the
      Gene Expression Omnibus database. A total of 93 and 114 differentially expressed
      genes (DEGs) were identified in NP and AF samples, respectively, using a limma
      software package for the R programming environment. Gene Ontology (GO) function
      enrichment analysis was performed to identify the associated biological functions
      of DEGs in IDD, which indicated that the DEGs may be involved in various
      processes, including cell adhesion, biological adhesion and extracellular matrix
      organization. Pathway enrichment analysis using the Kyoto Encyclopedia of Genes
      and Genomes (KEGG) demonstrated that the identified DEGs were potentially
      involved in focal adhesion and the p53 signaling pathway. Further analysis
      revealed that there were 35 common DEGs observed between the two regions (NP and
      AF), which may be further regulated by 6 clusters of microRNAs (miRNAs) retrieved
      with WebGestalt. The genes in the DEG-miRNA regulatory network were annotated
      using GO function and KEGG pathway enrichment analysis, among which extracellular
      matrix organization was the most significant disrupted biological process and
      focal adhesion was the most significant dysregulated pathway. In addition, the
      result of protein-protein interaction network modules demonstrated the
      involvement of inflammatory cytokine interferon signaling in IDD. These findings
      may not only advance the understanding of the pathogenesis of IDD, but also
      identify novel potential biomarkers for this disease.

PMID- 29039501
TI  - Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target
      of rapamycin C1 signaling pathway.
AB  - Osteoarthritis (OA) is the most common disease of the joints, and is
      characterized by the breakdown of cartilage and degradation of the extracellular
      matrix. OA causes a high level of patient suffering and incurs large societal
      costs; however, the current strategies for treating OA are restricted due to
      limited understanding of the underlying molecular and cellular mechanisms. In the
      present study, the beneficial effects of isoimperatorin (Iso) were investigated
      using an experimental mouse model of OA, and its mechanism of action on primary
      chondrocytes was elucidated. Destabilization of the medial meniscus was performed
      on 8-week-old male mice to induce OA in the knees. Iso (500 mg/g/day) was
      intragastrically administered for 4 weeks. Degeneration of articular cartilage
      was assessed by histology using the Osteoarthritis Research Society International
      scoring system. The expression of matrix metalloproteinase (MMP)13, Runt-related
      transcription factor (Runx)2, type X collagen (Col X) and vascular endothelial
      growth factor (VEGF) in the knee joints was examined by immunohistochemistry. In
      vitro, murine primary chondrocytes were treated with various concentrations of
      Iso, followed by 10 ng/ml interleukin-1. The mRNA expression levels of MMP13,
      Runx2, Col X and VEGF were determined by reverse transcription-quantitative
      polymerase chain reaction. The levels of autophagy and mammalian target of
      rapamycin (mTOR) signaling were determined by western blotting. Iso significantly
      ameliorated the severity of articular cartilage degradation in mice with
      experimental OA. The expression levels of MMP13, Runx2, Col X and VEGF were
      reduced in Iso-treated mice. In murine primary chondrocytes, Iso also reduced
      MMP13, Runx2, Col X and VEGF expression, and activated autophagy by
      downregulating the mTOR complex 1 (mTORC1) signaling pathway. Therefore, the
      results of the present study demonstrated that Iso ameliorates OA-induced
      pathological alterations by delaying chondrocyte deterioration, activating
      autophagy and inhibiting mTORC1, which suggests that Iso may have therapeutic
      potential for attenuating articular cartilage degradation and treating OA.

PMID- 29039503
TI  - Inhibitory effects of lupane-type triterpenoid saponins from the leaves of
      Acanthopanax gracilistylus on lipopolysaccharide-induced TNF-alpha, IL-1beta and
      high-mobility group box 1 release in macrophages.
AB  - Acanthopanax gracilistylus (AGS) has long been used in traditional Chinese
      medicine for the treatment of various inflammatory diseases. 3-O-beta-D
      glucopyranosyl 3alpha, 11alpha-dihydroxylup-20(29)-en-28-oic acid, acantrifoside
      A, acankoreoside D, acankoreoside B and acankoreoside A are major lupane-type
      triterpenoid saponins derived from AGS. In the present study, these five saponins
      were isolated from AGS by chromatography and their anti-inflammatory activities
      were investigated in lipopolysaccharide (LPS)-treated RAW264.7 macrophages. Cell
      viability was evaluated by MTT assay. Tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-1beta and NF-kappaB p65 were measured by ELISA. The gene
      expression levels of TNF-alpha and IL-1beta was detected by reverse-transcription
      polymerase chain reaction. And high-mobility group box 1 (HMGB1) were analyzed by
      western blotting. The results demonstrated that these five saponins significantly
      suppressed LPS-induced expression of TNF-alpha and IL-1beta at the mRNA and
      protein level in RAW264.7 cells. Further analysis revealed that acankoreoside A
      and acankoreoside B were able to reduce the secretion of HMGB1 and NF-kappaB
      activity induced by LPS in RAW264.7 macrophages. Taken together, these results
      suggested that the anti-inflammatory activity of AGS-derived saponins may be
      associated with the downregulation of TNF-alpha and IL-1beta, and the 'late
      phase' proinflammatory cytokine HMGB1, via negative regulation of the NF-kappaB
      pathway in RAW264.7 cells.

PMID- 29039502
TI  - Long non-coding RNA HOTTIP promotes hepatocellular carcinoma tumorigenesis and
      development: A comprehensive investigation based on bioinformatics, qRT-PCR and
      meta-analysis of 393 cases.
AB  - HOTTIP functions as an independent biomarker in multiple cancers. However, the
      role of HOTTIP in hepatocellular carcinoma (HCC) remains unclear. In this study,
      we sought to investigate the HOTTIP expression in HCC and normal liver. We
      combined quantitative reverse transcription-polymerase chain reactions (qRT-PCR),
      Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), Multi
      Experiment Matrix (MEM) and Oncomine database to assess the clinical role and the
      potential molecular mechanism of HOTTIP in HCC. Furthermore, a meta-analysis was
      performed to evaluate the relationship between HOTTIP and HCC tumorigenesis and
      development. Additionally, bioinformatics analysis, which contained Gene Ontology
      (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and network analysis, were
      applied to investigate the underlying functions, pathways and networks of the
      potential genes. HOTTIP was obviously upregulated in HCC. A statistically
      significant higher expression of HOTTIP was found in TNM (III +IV), age (>=60),
      sex (male), race (white) and cirrhosis (no) compared to the control groups
      (P<0.05). Furthermore, the meta-analysis of 393 cases from multiple centers
      indicated that HOTTIP had high diagnostic value in HCC. Additionally, according
      to GO and KEGG analyses, we found that the most strongly enriched functional
      terms were gland development, transcription factor activity and extrinsic to
      membrane. Also, the HOTTIP co-expressed genes were significantly related to PPAR
      signaling pathway. We speculate that HOTTIP might play a vital part in HCC via
      regulating various pathways, especially PPAR signaling pathway. However, the
      detailed mechanism should be confirmed by functional experiments.

PMID- 29039504
TI  - Inhibitory effects of ubiquitination of synoviolin by PADI4.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory articular disease that is
      characterized by synovial hyperplasia. A number of signaling pathways are
      associated with the development and induced symptoms of RA. Notably, patients
      with RA have increased protein citrullination and generation of auto-antibodies
      against citrullinated proteins. Genome wide association studies have revealed
      that peptidyl-arginine deiminase 4 (PADI4) is an enzyme implicated in
      citrullination in the RA synovium. Autoantibodies targeting citrullinated
      proteins are used as diagnostic markers in patients with RA. The functions
      associated with citrullinated proteins are thought to induce autoimmunity,
      however, the regulatory mechanisms of citrullination via PADI4 are unclear. The
      group has previously cloned an E3 ubiquitin ligase, synoviolin (SYVN1), from the
      RA synovium, demonstrating that SYVN1 serves critical roles in synovial
      hyperplasia. The data indicated that the endoplasmic reticulum (ER) associated
      degradation system, which involves SYVN1, may have important roles in the
      proliferation of synoviocytes. In addition, ubiquitination by SYVN1 is associated
      with fibrosis, inflammation and cytokine production via the regulation of ER
      stress signals and quality control of proteins. The present study investigated
      the crosstalk between the representative post-translational signaling processes,
      citrullination and ubiquitination. The results revealed that PADI4 interacted
      with SYVN1 directly and that overexpression of PADI4 suppressed the
      ubiquitination of proteins. Thus, a reduction in ER stress induced by PADI4 may
      abrogate the initiation of chronic RA by suppressing the proliferative signals of
      RA synoviocytes.

PMID- 29039505
TI  - Characterization of acid-tolerance-associated small RNAs in clinical isolates of
      Streptococcus mutans: Potential biomarkers for caries prevention.
AB  - Streptococcus mutans is a cariogenic bacterium that contributes to dental caries
      due to its ability to produce lactic acid, which acidifies the local environment.
      The potential of S. mutans to respond to environmental stress and tolerate low pH
      is essential for its survival and predominance in caries lesions. Small noncoding
      RNAs (sRNAs) have been reported to be involved in bacterial stress and virulence.
      Few studies have investigated the sRNAs of S. mutans and the function of these
      sRNAs remains to be elucidated. In the present study, the association between
      sRNA133474 and acid tolerance, including potential underlying mechanisms, were
      investigated within clinical strains of S. mutans. From pediatric dental plaques,
      20 strains of S. mutans were isolated. An acid killing assay was performed to
      analyze acid tolerance of S. mutans. Expression patterns of sRNA133474 were
      investigated during various growth phases under various acidic conditions via
      reverse transcription-quantitative polymerase chain reaction. RNA predator and
      Kyoto Encyclopedia of Genes and Genomes analyses were performed to predict target
      mRNAs of sRNA133474 and to examine the involvement of putative pathways of target
      mRNAs, respectively. The results of the present study demonstrated that
      sRNA133474 activity was growth phase-dependent, and two distinct expression
      patterns were identified in 10 clinical strains. At pH 5.5 and 7.5 the expression
      levels of sRNA133474 were significantly different, and high-acid tolerant strains
      exhibited reduced expression levels of sRNA133474 compared with low-acid tolerant
      strains. A correlation between sRNA133474 expression levels and acid tolerance
      was observed in 20 clinical isolates of S. mutans (r=-0.6298, P<0.01). Finally,
      five target mRNAs (liaS, liaR, comE, covR and ciaR) involved in the two-component
      system (TCS) were selected for further evaluation; the expression levels of three
      target mRNAs (liaR, ciaR and covR) were negatively correlated with sRNA133474
      expression levels. In conclusion, the results of the present study suggested that
      S. mutans may utilize sRNA133474 to orchestrate TCSs for optimal adaption to
      acidic pH in clinical strains.

PMID- 29039506
TI  - Hypothermic machine perfusion ameliorates inflammation during ischemia
      reperfusion injury via sirtuin-1-mediated deacetylation of nuclear factor-kappaB
      p65 in rat livers donated after circulatory death.
AB  - Hypothermic machine perfusion (HMP) effectively reduces ischemia-reperfusion
      injury (IRI) in livers donated after circulatory death (DCD) when compared with
      cold storage (CS). However, the underlying mechanisms remain unclear. The current
      study aimed to investigate the cellular mechanisms by which HMP ameliorates the
      inflammatory response during IRI. Adult male Sprague-Dawley rat livers were
      exposed to 30 min of warm ischemia following cardiac arrest and preserved by CS
      or HMP for 3 h (n=3 per group). The severity of IRI was assessed in vitro on
      normothermic reperfusion for 2 h, and intrahepatic resistance (IHR) and bile
      production were subsequently recorded. The perfusate was analyzed for
      transaminase leakage and oxygen consumption. Livers were subsequently subjected
      to histological examination, and measurement of adenosine triphosphate (ATP)
      levels, malondialdehyde (MDA) content, superoxide dismutase (SOD) activity,
      nicotinamide adenine dinucleotide (NAD)+ levels and the ratio of NAD+/NADH. In
      addition, the protein expression of sirtuin-1 (SIRT-1), acetylated-nuclear factor
      kappaB (NF-kappaB) p65 and NF-kappaB p65 was detected by western blotting, and
      the mRNA expression of the inflammatory cytokines interleukin (IL)-6 and tumor
      necrosis factor (TNF)-alpha was determined by reverse transcription-quantitative
      polymerase chain reaction. Compared with CS, HMP resulted in significantly lower
      IHR, transaminase leakage and MDA levels, and higher oxygen consumption, ATP
      levels and SOD activity. In addition, improved preservation of hepatic histology
      was observed in HMP compared with CS. The mRNA expression of NF-kappaB p65, IL-6
      and TNF-alpha was significantly decreased in the HMP group compared with CS
      samples. Under HMP preservation, SIRT-1 activity and protein expression were
      increased, while the protein expression of acetylated-NF-kappaB p65 was
      decreased, compared with CS. These results indicate that HMP may reduce the
      inflammatory response during IRI via SIRT-1-mediated deacetylation of NF-kappaB
      p65. These findings may provide a theoretical basis for the clinical application
      of HMP as an effective strategy to preserve DCD livers.

PMID- 29039507
TI  - Effect of the adenovirus-mediated Wip1 gene on lumbar intervertebral disc
      degeneration in a rabbit model.
AB  - The present study aimed to investigate the effect of the adenovirus-mediated wild
      type p53-induced protein phosphatase 1 (Wip1) gene on lumbar disc degeneration
      (LDD) in a rabbit model. Adult New Zealand white rabbits were used as
      experimental subjects. The rabbits were divided into LDD groups (groups A-C of
      rabbit models of LDD) and control groups (groups D-F of normal rabbits). The
      animals in groups A and D were injected with the Wip1 gene vector, those in
      groups B and E were injected with an empty vector, and those in groups C and F
      were injected with phosphate-buffered saline. Type II collagen was detected using
      a streptavidin-biotin complex immunohistochemistry method. Postoperative X-ray
      imaging showed a significant increase in the recovery of rabbits from group A,
      compared with those from groups B and C. The nucleus pulposus proteoglycan
      content of the intervertebral discs (L2-3, L3-4 and L4-5) of group A remained
      higher, compared with the content in groups B and C, and the values in groups B
      and C differed from those of groups E and F. At 3, 6 and 9 weeks post-injection,
      the content of type II collagen of intervertebral discs (L2-3, L3-4 and L4-5) in
      group A differed from groups B and C, and the values in groups A-C remained
      lower, compared with those in groups D-F. The Wip1 gene exhibited a therapeutic
      effect in the treatment of LDD.

PMID- 29039508
TI  - Transformation of liver cells by 3-methylcholanthrene potentiates oxidative
      stress via the downregulation of glutathione synthesis.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are widespread contaminants resulting
      from the incomplete combustion of organic materials in the environment. The
      primary concern for the hazardous effect of PAHs is their ability to activate the
      pathway linked to the aryl hydrocarbon receptor (AhR) and lead to carcinogenesis.
      While previous research has demonstrated that oxidative stress plays a key role
      in the AhR-dependent toxic response, the effect of PAHs on the biosynthesis of
      glutathione (GSH), which is a powerful endogenous antioxidant, has not been
      extensively investigated. In the present study, we utilized a global metabolomic
      approach, via high resolution magic angle spinning nuclear magnetic resonance
      spectroscopy, and identified significant metabolome differences between non
      tumorigenic liver cells (BNL CL.2; CL2) and transformed liver cells (BNL 1MEA.
      7R.1; 1MEA) chronically exposed to 3-methylcholanthrene (3MC), a well-known
      carcinogenic PAH. A significant change that was observed, was a lower GSH level
      in 1MEA cells compared with that in CL2 cells. This was contrasted by increased
      levels of precursor metabolites for GSH synthesis, such as S-adenosylmethionine
      and cysteine. These changes were accompanied by a significantly reduced
      expression of gamma-glutamylcysteine ligase (GCL), known to be the rate-limiting
      step of GSH synthesis. Furthermore, the protein level of cysteine dioxygenase was
      downregulated; however, the concentration of taurine was unaltered. Therefore,
      the present study demonstrated that cells transformed by chronic exposure to 3MC
      exhibited inhibition of GSH biosynthesis by suppression of GCL protein expression
      and reduction of cysteine availability, which may subsequently render cells
      vulnerable to oxidative stress.

PMID- 29039509
TI  - Evaluation of a novel dry eye model induced by oral administration of
      finasteride.
AB  - Dry eye is a common eye disease, and suitable animal models are indispensable for
      investigating the pathogenesis and developing treatments for dry eye. The present
      study was conducted to develop an androgen deficiency dry eye model induced by
      finasteride, and to evaluate ocular surface status and inflammatory cytokine gene
      expression in the lacrimal gland using a cytokine antibody array system. The
      results revealed that the antiandrogenic drug finasteride induced significant
      tear deficiency, and the histopathology results revealed significant inflammatory
      cell infiltration in the lacrimal gland. The cytokine antibody array system
      identified increased B7-2 (also known as cluster of differentiation 86),
      interleukin (IL)-1beta, IL-4, IL-6, IL-10, matrix metalloproteinase-8, Fas
      ligand, tumor necrosis factor (TNF)-alpha and metalloproteinase inhibitor 1
      levels in the lacrimal gland of the dry eye model. These cytokines were validated
      as candidate markers through the use of western blot analysis and reverse
      transcription-quantitative polymerase chain reaction. Both analyses confirmed a
      significant increase in proinflammatory cytokines, including IL-1beta, IL-6 and
      TNF-alpha, and anti-inflammatory cytokines, including IL-4 and IL-10. The
      aforementioned data suggested that inflammation in antiandrogenic models resulted
      from a balance between inflammatory and anti-inflammatory responses. Thus, direct
      finasteride administration may produce an applicable model for dry eye mediated
      by androgen deficiency. In addition, there may be a correlation between sex,
      steroid deficiency and the inflammatory response. The findings of the present
      study have provided useful information for the pathogenesis and diagnosis of dry
      eye mediated by androgen deficiency.

PMID- 29039510
TI  - Homocysteine-induced oxidative stress through TLR4/NF-kappaB/DNMT1-mediated LOX-1
      DNA methylation in endothelial cells.
AB  - Atherosclerosis (AS) is a progressive disease of multifactorial origin, which
      occurs in response to endothelial injury. Increased homocysteine (Hcy) is
      considered a major cause of endothelial dysfunction, oxidative stress and DNA
      methylation; however, the mechanisms remain to be fully elucidated. The aim of
      the present study was to investigate whether Hcy causes injury to endothelial
      cells (ECs) by the effect of lectin-like oxidized-low density lipoprotein
      receptor-1 (LOX-1) DNA methylation through toll-like receptor 4(TLR4)/nuclear
      factor (NF)-kappaB/DNA methyltransferase (DNMT)1. The ECs were treated with
      different concentrations of Hcy, and it was found that Hcy promoted the
      expression of TLR4, leading to EC injury. The effect of oxidative stress was
      analyzed by measuring superoxide dismutase, malondialdehyde and hydrogen peroxide
      in the ECs. In addition, the association between NF-kappaB and DNMT1 was examined
      by treatment of the ECs with pyrrolidine dithiocarbamate (PDTC). The results
      suggested that Hcy induced LOX-1 DNA hypomethyaltion to promote the expression
      levels of LOX-1. Taken together, Hcy injured the ECs through the effect of
      methylation and trans-sulfuration metabolism of LOX-1 through TLR4/NF
      kappaB/DNMT1. Following injury to the ECs, lipids, particularly ox-LDL,
      accumulated in the sub-endothelial layer to promote the formation of AS.

PMID- 29039511
TI  - TRAIL mutant membrane penetrating peptide alike (TMPPA) TRAIL-Mu3 enhances the
      antitumor effects of TRAIL in vitro and in vivo.
AB  - The aim of the present study was to prepare a tumor necrosis factor ligand
      superfamily member 10 (TRAIL) mutant membrane penetrating peptide alike (TMPPA),
      TRAIL-Mu3, and to investigate its antitumor effects in colorectal cancer in vitro
      and in vivo. The pMD19/TRAIL plasmid with designed primers was amplified to
      construct the target gene; it was ligated with an expression plasmid and the
      expression was confirmed. Subsequently, TRAIL-Mu3 was purified and further
      confirmed by western blot analysis. Immunofluorescence analysis was used to
      detect the distribution of TRAIL-Mu3 in colorectal cancer cells. In addition, the
      present study investigated the antitumor effects of TRAIL-Mu3 on colorectal
      cancer in vitro and in vivo. A novel TMPPA, TRAIL-Mu3, was synthesized in the
      present study. Following a series of detection experiments, it was confirmed that
      the TRAIL-Mu3 gene was obtained and was able to express TRAIL-Mu3 successfully.
      The immunofluorescence analysis demonstrated that TRAIL-Mu3 exhibited a markedly
      enhanced affinity to the colorectal cancer cell surface. In addition, TRAIL-Mu3
      exerted stronger antitumor effects, compared with TRAIL, on colorectal cancer in
      vitro and in vivo.

PMID- 29039512
TI  - Sporamin suppresses growth of human esophageal squamous cell carcinoma cells by
      inhibition of NF-kappaB via an AKT-independent pathway.
AB  - The aim of the present study was to determine whether sporamin, a trypsin
      inhibitor, suppresses the growth of human esophageal squamous cell carcinoma
      (ESCC) cells in vitro. Sporamin treatment led to the suppression of viability and
      proliferation of human ESCC cell lines, EC9706 and EC109, as determined by MTT
      and [3H] thymidine incorporation assays, respectively. Flow cytometry and
      fluorescence microscopy demonstrated that sporamin significantly induced
      apoptosis in EC9706 and EC109 cells. Western blotting demonstrated that sporamin
      downregulated the expression of Bcl-2 and Bcl-2 like 1, and upregulated the
      expression of Bcl-2-associated X in EC9706 and EC109 cells. In addition, marked
      inhibition of nuclear factor (NF)-kappaB activation was observed in sporamin
      treated EC9706 and EC109 cells by an electrophoretic mobility shift assay.
      Sporamin treatment also resulted in reduced expression levels of phosphorylated
      (p)-NF-kappaB inhibitor alpha and nuclear NF-kappaB p65. However, the expression
      levels of p-protein inase (AKT) and its downstream target, p-p70 S6 kinase, were
      not markedly altered following sporamin treatment. In conclusion, sporamin may
      suppress the growth of human ESCC cells via NF-kappaB-dependent and AKT
      independent mechanisms and may act as a promising natural therapeutic agent for
      the treatment of human ESCC.

PMID- 29039513
TI  - BIRC5 is a novel target of peroxisome proliferator-activated receptor gamma in
      brain microvascular endothelium cells during cerebral ischemia.
AB  - Cerebral ischemia is a leading cause of ischemic stroke, which may lead to severe
      disability and mortality worldwide. There are some key factors concerned in
      cardioprotection, such as peroxisome proliferator-activated receptor gamma
      (PPARgamma), a ligand binding transcription factor involved in various biological
      functions including atherosclerosis, vascular dysfunction and hypertension, and
      baculoviral IAP repeat-containing 5 (BIRC5), which may protect human brain
      endothelial cells from ischemia-induced apoptosis. To determine the potential
      roles of PPARgamma in brain microvascular endothelial (bEnd.3) cells during
      cerebral ischemia and the relationship between PPARgamma and BIRC5, a cerebral
      ischemia model was established with bEnd.3 cells cells by oxygen-glucose
      deprivation (OGD) treatment. OGD treatment reduced proliferation and enhanced
      apoptosis of bEnd.3 cells in a time-dependent manner. PPARgamma expression levels
      were decreased in bEnd.3 cells following OGD treatment. Upregulation of PPARgamma
      expression protected bEnd.3 cells from ischemia injury and also upregulated BIRC5
      expression. PPARgamma-specific binding sites in the BIRC5 promoter were predicted
      bioinformatically and verified by luciferase reporter experiments. Results from
      electrophoretic mobility shift/supershift and chromatin immunoprecipitation
      assays suggested that BIRC5 may be a novel target of PPARgamma transcriptional
      regulation during ischemic injury. The present results indicated that PPARgamma
      may serve a protective role on bEnd.3 cells and that BIRC5 may be a downstream
      target of PPARgamma regulation during cerebral ischemia.

PMID- 29039514
TI  - 5,6,7,3',4',5'-Hexamethoxyflavone inhibits growth of triple-negative breast
      cancer cells via suppression of MAPK and Akt signaling pathways and arresting
      cell cycle.
AB  - Natural components continue to be an important source for the discovery and
      development of novel anticancer agents. Polymethoxyflavones are a class of
      flavonoids found in citrus fruits and medicinal plants used in traditional
      medicine. In the present study, the anticancer activity of the well-known
      nobiletin (5,6,7,8,3',4'-hexamethoxyflavone) was compared against its less
      studied structural isomer 5,6,7,3',4',5'-hexamethoxyflavone. These compounds were
      evaluated on the Hs578T triple-negative breast cancer cell line and its more
      migratory subclone Hs578Ts(i)8. 5,6,7,3',4',5'-hexamethoxyflavone was found to be
      less toxic than nobiletin, while a similar growth inhibitory effect was observed
      after 72 h. Additionally, 5,6,7,3',4',5'-hexamethoxyflavone arrested the cell
      cycle in the G2/M phase, while no effect was observed on apoptosis or the
      migratory behavior of these cells. Furthermore, mechanistic studies revealed that
      the growth inhibition was concomitant with reduced phosphorylation levels of
      signaling molecules in the MAPK and Akt pathways as well as cell cycle
      regulators, involved in regulating cell proliferation, survival and cell cycle.
      In summary, the present study is the first to report on the anticancer activities
      of 5,6,7,3',4',5'-hexamethoxyflavone and to provide evidence that this flavone
      could have a greater potential than nobiletin for prevention or treatment of
      triple- negative breast cancer.

PMID- 29039516
TI  - Baicalin alleviates H2O2-induced injury of H9c2 cardiomyocytes through
      suppression of the Wnt/beta-catenin signaling pathway.
AB  - Baicalin is one of the active ingredients extracted from the dry root of
      Scutellaria baicalensis Georgi, which has been reported to be effective in
      preventing myocardial ischemia reperfusion injury. However, the mechanisms
      underlying its cardioprotective activities remain to be elucidated. In the
      present study, H2O2-treated cardiomyocyte H9c2 cell line served as an in vitro
      model of oxidation-damaged cardiomyocytes to evaluate the effects of baicalin on
      the cardiac injury, and to investigate the underlying molecular mechanism. The
      results of the TOPFlash/Renilla reporter gene assay indicated that baicalin
      significantly suppressed the activation of proto-oncogene Wnt-1 (Wnt)/beta
      catenin in 293 cells, in a dose dependent manner. In addition, baicalin
      significantly inhibited H2O2-induced loss of H9c2 cell viability in MTT assay.
      Furthermore, western blotting analysis demonstrated that baicalin markedly
      attenuated H2O2-induced cell apoptosis, as demonstrated by the down-regulation of
      cleaved caspase-3 and the increase in the apoptosis regulator Bcl-2 (Bcl
      2)/apoptosis regulator BAX (Bax) ratio following baicalin treatment in H2O2
      treated H9c2 cells. Furthermore, baicalin markedly decreased the expression of
      beta-catenin and downstream Axin-2 and myc proto-oncogene protein in H2O2-treated
      H9c2 cells. Knockdown of beta-catenin expression inhibited H2O2-induced cell
      apoptosis. Finally, LiCl (a beta-catenin stabilizer) induced apoptosis of H9c2
      cells by upregulating the expression of beta-catenin, which was significantly
      neutralized by the treatment with baicalin. Taken together, it is hypothesized
      that baicalin exerts cardioprotective effects via suppression of the Wnt/beta
      catenin signaling pathway.

PMID- 29039515
TI  - Calcitonin gene-related peptide induces IL-6 expression in RAW264.7 macrophages
      mediated by mmu_circRNA_007893.
AB  - Several circular RNAs (circRNAs) may have role important roles in biological
      processes, however, there is limited knowledge of circRNAs and their potential
      functions in RAW264.7 macrophages. The present study aimed to examine the
      expression of circRNAs and explore their effects on interleukin-6 (IL-6)
      expression induced by calcitonin gene-related peptide (CGRP) in RAW264.7
      macrophages. To identify circRNAs, the circRNA expression was measured in
      macrophages with or without CGRP stimulation. The interaction between circRNAs
      and microRNAs (miRs) were then identified using bioinformatic software and
      networks. In the current study, it was demonstrated that CGRP increased the
      expression of IL-6 mRNA in a dose- and time-dependent manner. Furthermore,
      mmu_circRNA_007893 was significantly increased in the CGRP-stimulated
      macrophages. Silencing of mmu_circRNA_007893, IL-6 mRNA expression was
      significantly decreased, whereas mmu-miR-485-5p expression was markedly
      increased. Furthermore, when overexpression of mmu-miR-485-5p, IL-6 mRNA was
      markedly decreased. The results demonstrated that CGRP-induced IL-6 mRNA
      expression was mediated by mmu_circRNA_007893, and mmu_circRNA_007893 functioned
      as an endogenous mmu-miR-485-5p sponge as part of induction of IL-6 mRNA
      expression.

PMID- 29039518
TI  - Leflunomide inhibits proliferation and tumorigenesis of oral squamous cell
      carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) is the most prevalent pathological cancer
      occurring in the head and neck area. Progress has previously been made regarding
      treatment strategies of OSCC, however the 5-year survival rate of these patients
      is only 50%. The present study examined if leflunomide (LEF), a drug primarily
      used for the treatment of rheumatoid arthritis, exhibited antitumor effects in
      OSCC. The results demonstrated that LEF inhibited cell proliferation and blocked
      the cell cycle at the S phase in OSCC cells, with upregulation of cyclin A
      protein expression. LEF reduced the expression of dihydroorotate dehydrogenase,
      which is an essential enzyme in the de novo pyrimidine biosynthetic pathway. LEF
      additionally inhibited colony formation in soft agar and reduced tumor growth in
      a xenograft model. The results suggested that LEF may act as a potential
      therapeutic agent in the treatment of OSCC in the future.

PMID- 29039517
TI  - MicroRNA-455 inhibits cell proliferation and invasion of epithelial ovarian
      cancer by directly targeting Notch1.
AB  - Ovarian cancer (OC) is the fifth leading cause of cancer-associated mortality
      among women in developed countries. Numerous microRNAs are aberrantly expressed
      in epithelial (E) OC, and are involved in EOC formation and progression. As such,
      microRNAs may be investigated as diagnostic and prognostic molecular biomarkers,
      and therapeutic targets for patients with EOC. For instance, microRNA-455 (miR
      455) is abnormally expressed in various types of human cancer. However, details
      on the expression level, biological roles and underlying mechanism of miR-455 in
      EOC remain unclear. In the present study, the expression of miR-455 in EOC was
      detected, and its association with clinical characteristics was analysed. The
      functional roles and underlying mechanisms of miR-455 in EOC were also
      investigated. The results revealed that miR-455 expression in EOC tissues and
      cell lines was significantly downregulated. Furthermore, miR-455 downregulation
      was correlated with tumor size, International Federation of Gynecology and
      Obstetrics stage and lymph node metastasis of patients with EOC. Restoration of
      miR-455 expression efficiently inhibited cell proliferation and invasion in
      vitro. Notch1 was identified as a direct target of miR-455 in EOC. The mRNA and
      protein expression levels of Notch1 were higher in EOC tissues compared with in
      normal ovarian epithelial tissues. Spearman's correlation analysis indicated that
      miR-455 expression was negatively correlated with the mRNA level of Notch1 in EOC
      tissues. Notch1 overexpression was able to restore the EOC cell proliferation and
      invasion abilities suppressed by miR-455. The present study provided evidence
      that the dysregulation of the miR-455/Notch1 signalling pathway may be essential
      for EOC occurrence and development. In addition, the results confirmed the tumor
      suppressive roles of miR-455 in modulating EOC proliferation and invasion through
      regulation of Notch1 expression. Thus, miR-455 may be a novel miRNA-based
      therapeutic target to treat patients with EOC.

PMID- 29039519
TI  - RUNX3 plays an important role in mediating the BMP9-induced osteogenic
      differentiation of mesenchymal stem cells.
AB  - Although bone morphogenetic protein 9 (BMP9) is highly capable of promoting the
      osteogenic differentiation of mesenchymal stem cells (MSCs) both in vitro and in
      vivo, the molecular mechanisms involved remain to be fully elucidated. Runt
      related transcription factor (RUNX)3 is an essential regulator of
      osteoblast/chondrocyte maturation. However, the exact role of RUNX3 in BMP9
      osteoinductive activity is unknown. In this study, we sought to investigate the
      functional role of RUNX3 in the BMP9-induced osteogenic differentiation of MSCs.
      We found that BMP9 upregulated the endogenous expression of RUNX3 in MSCs. The
      overexpression or/and knockdown of RUNX3 both increased the levels of alkaline
      phosphatase (ALP) a marker of BMP9-induced early osteogenic differentiation.
      Nevertheless, matrix mineralization, a marker of BMP9-induced late osteogenic
      differentiation was enhanced by the overexpression of RUNX3, whereas it was
      inhibited by the knockdown of RUNX3. The BMP9-induced expression of osteogenic
      pivotal transcription factors [inhibitor of differentiation (Id)3, distal-less
      homeobox 5 (DLX5) and RUNX2)] was further increased by the overexpression of
      RUNX3; however, it was reduced by the knockdown of RUNX3. However, the expression
      levels of Id1 and Id2 were both enhanced by the overexpression or/and knockdown
      of RUNX3. The BMP9-induced phosphorylation of Smad1/5/8 was increased with the
      overexpression of RUNX3, and yet was decreased with the knockdown of RUNX3.
      Collectively, our findings suggest that RUNX3 is an essential modulator of the
      BMP9-induced osteoblast lineage differentiation of MSCs.

PMID- 29039520
TI  - Concentration-dependent effects of paeoniflorin on proliferation and apoptosis of
      vascular smooth muscle cells.
AB  - Vascular smooth muscle cells (VSMCs) are an important component of arterial
      walls, and their dysfunction may serve an important role in the development of
      cardiovascular diseases, including atherosclerosis and restenosis. Paeoniflorin
      (PF) is a principal component of the commonly used traditional Chinese medicine,
      peonies. To the best of our knowledge, the effects of PF on apoptosis and
      proliferation of VSMCs and its underlying molecular mechanisms have not been
      widely reported. Therefore, the present study was designed to investigated this
      phenomenon. VSMCs were treated with different concentrations of PF (25, 50 and
      100 ug/ml) for 12, 24 or 48 h. The data demonstrated that PF treatment not only
      significantly decreased cell viability and DNA synthesis but also blocked G0/G1
      cell cycle progression. This effect was associated with a decreased expression of
      cyclin D1, cyclin E, cyclin-dependent kinase (CDK)4 and CDK2 as well as an
      upregulation of p21. Notably, a significant concentration-dependent decrease in
      the phosphorylation of p65 and nuclear factor of kappa light polypeptide gene
      enhancer in B-cells inhibitor-alpha (IkappaBalpha) was observed. In addition, it
      was demonstrated that PF promoted the apoptosis of VSMCs, which was associated
      with the increased expression of caspases. In conclusion, PF inhibited the
      proliferation of VSMCs by downregulating proteins associated with the nuclear
      factor-kappaB signaling pathway. Furthermore, it promoted the apoptosis of VSMCs
      by upregulating the expression of caspases. These results may be useful in
      improving the understanding of the molecular mechanisms underlying the apoptotic
      and anti-proliferative effects of PF on VSMCs, and facilitate the development of
      novel treatments for cardiovascular diseases.

PMID- 29039521
TI  - Antitumoral effect of arsenic compound, sodium metaarsenite (KML001), on multiple
      myeloma cells.
AB  - KML001 (sodium metaarsenite;NaAs2O3) is known to have antitumor activity against
      a variety of cancers. In this study, we examined its effect on multiple myeloma
      (MM). KML001 reduced the growth of all MM cell lines examined with an IC50 of
      5x10-8 M. Exposure to KML001 (5x10-8 M) decreased levels of cyclins A/B1/D1/E1,
      CDK2/4/6 in U266 cells and increased the p21 and p27 levels. Furthermore, p21
      became bound to CDK2/4/6, resulting in a reduction of CDK2/4/6 kinase activity.
      The cleaved forms of Bcl-2, and caspases-3, -8 and -9 were detected, and the anti
      apoptotic molecule, Bax, also increased. Activation of STAT1/3, NF-kappaB (p65
      and p50 subunits), pAKT and pERK decreased, and p-PTEN increased. There was also
      a significant reduction of hTERT at 12 h and upregulation of gamma-H2AX and
      CHK1/2 molecules at 24 h. Thus, KML001 appears to have antitumor activity against
      MM by inhibiting various oncogenic signaling pathways. It may be useful for
      treating MM.

PMID- 29039522
TI  - [Retracted] Atorvastatin protects cardiomyocytes against OGD/R-induced apoptosis
      by inhibiting miR-199a-5p.
AB  - Following the publication of this article, the authors find that they are not
      able to reproduce certain of the results presented in this paper. Consequently,
      the authors have decided to retract this paper from the publication. All of the
      authors agree to this retraction. The authors sincerely regret this decision, and
      apologize to the Editor and to the readership of the Journal for any
      inconvenience caused. [The original article was published in Molecular Medicine
      Reports 16: 3807-3816, 2017; DOI: 10.3892/mmr.2017.7084].

PMID- 29039523
TI  - Analysis of MEN1 c.482G>A (p.Gly161Asp) mutation in a pedigree with familial
      multiple endocrine neoplasia type 1.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder
      characterized by the development of neuroendocrine tumors, which in turn are
      caused by mutations in the MEN1 gene. In the present study, a case of a 46-year
      old woman who was clinically diagnosed with MEN1 based on the presence of
      prolactinoma and bilateral parathyroid adenoma was reported. The patient's serum
      prolactin (PRL) levels were successfully controlled via bromocriptine therapy,
      and the serum levels of calcium and intact parathyroid hormone (PTH) reduced one
      day following parathyroidectomy. Genetic testing revealed a missense mutation
      c.482G>A (p.Gly161Asp) in exon 3 of the MEN1 gene, and it led to the
      identification of two carriers in the pedigree (patient's elder sister and
      brother). Both of the carriers revealed to have high blood calcium, PTH and PRL.
      The mutation identified in this pedigree has never been reported in China. The
      sequence alignments and tertiary structure of menin protein were made by
      Polyphen2, SNPs3D, and SIFT, which were used to predict the function of mutant
      menin. Since the mutant menin may interfere with the menin-JunD or menin-Smad3
      interactions, further investigations are necessary to explore the function of
      mutant protein. In view of that, identification of mutations and longtime follow
      up are important for patients with a pedigree clearly indicating MEN1.

PMID- 29039524
TI  - Synergistic effects of baicalein with gemcitabine or docetaxel on the
      proliferation, migration and apoptosis of pancreatic cancer cells.
AB  - Baicalein, a type of flavonoids extracted from Scutellaria baicalensis Georgi,
      has been reported to be a very promising drug for pancreatic cancer. However, it
      is unclear whether combination of baicalein with gemcitabine or docetaxel is
      synergistic to the treatment for pancreatic cancer (PC). We investigated the
      combinational effects of baicalein with gemcitabine or docetaxel on
      proliferation, cell cycle, migration and apoptosis of human PC cells.
      Administration of baicalein alone significantly inhibit the proliferation of PC
      cells. Notably, when it is combined with gemcitabine or docetaxel, combination
      index (CI) values calculated by Calcusyn software are smaller than 1, indicating
      the synergism of baicalein with gemcitabine or docetaxel for the treatment of PC
      cells. Consistently, EdU assay showed that administration of baicalein
      significantly enhanced the capacity of gemicitabine to inhibit proliferation of
      PC cells. Cell cycle analysis showed that high-concentration of baicalein was
      able to arrest PC cells in the S phase. Furthermore, low concentration of
      baicalein in combination with either gemcitabine or docetaxel exhibited strong
      suppression on the migration of PC cells. A further study using transmission
      electron microscope (TEM), DAPI staining and western blot showed that baicalein
      induced-apoptosis of PC cells might be via caspase-3/PARP signaling pathway.
      Notably, combination treatment was able to induce more severe cell apoptosis of
      PC cells. In conclusion, baicalein exhibited synergistic effects with gemcitabine
      or docetaxel on the treatment of PC cells.

PMID- 29039526
TI  - Promoting effects of IL-23 on myocardial ischemia and reperfusion are associated
      with increased expression of IL-17A and upregulation of the JAK2-STAT3 signaling
      pathway.
AB  - Interleukin (IL)-23, as a novel pro-inflammatory cytokine, is important in
      several inflammatory diseases, including myocardial ischemia and reperfusion
      (I/R) injury, however, the underlying mechanism remains to be elucidated. The
      present study was designed to investigate the specific role of IL-23 in
      myocardial I/R injury, and whether the Janus kinase 2/signal transducer and
      activator of transcription 3 (JAK2-STAT3) signaling pathway, one of the important
      downstream signaling pathways of IL-23, and the IL-17A downstream pro
      inflammatory cytokine, were involved. Anesthetized rats underwent different
      treatments with adenovirus (Ad) vectors (Ad-GFP, Ad-IL-23, Anti-IL-23 or Ad-IL
      23+AG490) and were then subjected to ischemia for 30 min prior to 4 h
      reperfusion. The effects of the upregulation and downregulation of IL-23 on
      myocardial injury, inflammatory responses in myocardial tissue, and myocardial
      apoptosis were measured accordingly. In addition, the levels of phosphorylated (P
      )JAK2 and P-STAT3 were measured to assess the activity of the JAK2-STAT3
      signaling pathway. The results demonstrated that there was an increased
      expression of IL-23 in the myocardial tissue exposed to myocardial I/R injury
      (P<0.05). The upregulation of IL-23 significantly increased the infarct size and
      the expression levels of lactate dehydrogenase and creatine kinase (P<0.05). The
      upregulation of IL-23 significantly increased inflammatory responses, as
      reflected by the high expression levels of IL-17A, IL-6, tumor necrosis factor
      alpha in the myocardial tissues (P<0.05). Furthermore, the upregulation of IL-23
      significantly facilitated the decrease in the B-cell lymphoma 2 (Bcl-2)/Bcl-2
      associated X protein ratio, and the increases in the myocardial apoptotic index
      and expression of caspase-3 induced by myocardial I/R (P<0.05). IL-23 also
      activated the JAK2-STAT3 signaling pathway, upregulating the expression levels of
      P-JAK2 and P-STAT3 in the myocardial tissues (P<0.05). Treatment with AG490, an
      inhibitor of JAK2-STAT3, partially attenuated the pro-inflammatory and pro
      apoptotic effects of IL-23 (P<0.05). The results of the present study suggested
      that IL-23 aggravated myocardial I/R injury by promoting inflammatory responses
      and myocardial apoptosis, which may be associated with high expression levels of
      IL-17A and upregulation of the JAK2-STAT3 signaling pathway.

PMID- 29039525
TI  - The association between parathyroid hormone 1-34 and the Wnt/beta-catenin
      signaling pathway in a rat model of osteoarthritis.
AB  - The aim of the current study was to determine the effect of parathyroid hormone
      (PTH) 1-34 on cartilage degeneration, and the association between PTH 1-34 and
      factors associated with the Wnt/beta-catenin pathway following anterior cruciate
      ligament and medial meniscectomy-induced osteoarthritis (OA) in rats. A total of
      64 Sprague-Dawley rats were randomly divided into the following four groups: Sham
      operated rats with normal saline (NS)-treatment (n=16); anterior cruciate
      ligament transection with partial medial meniscectomy (ACLT + MMx) rats with NS
      treatment (n=16); sham-operated rats treated with PTH 1-34 (n=16); and ACLT + MMx
      rats treated with PTH 1-34 (n=16). PTH (15 ug/kg/day) was administered via
      subcutaneous injection 5 days per week from the first postoperative day for 2 or
      6 weeks. Staining with hematoxylin and eosin and safranin O, and a scoring system
      modified by Mankin were used to assess the histopathological features of
      cartilage. The present study detected the expression of PTH 1 receptor (PTH1R),
      sclerostin, dickkopf Wnt signaling pathway inhibitor 1 (DKK1), beta-catenin and
      runt-related transcription factor 2 (RUNX2) in cartilage by immunohistochemical
      analysis to determine the association between PTH 1-34 and factors associated
      with the Wnt/beta-catenin pathway. Reverse transcription-quantitative polymerase
      chain reaction (RT-qPCR) was performed to detect the mRNA expression levels of
      PTH1R and beta-catenin in cartilage. Histological analysis demonstrated that
      cartilage degeneration was present post-surgery and gradually increased over
      time. PTH 1-34 reduced the Mankin scores in ACLT + MMx rats compared with the NS
      treated ACLT + MMx rats. Immunohistochemistry and RT-qPCR analysis demonstrated
      that, in cartilage, PTH 1-34 treatment increased the mRNA expression and protein
      levels of PTH1R and beta-catenin, and decreased protein levels of sclerostin,
      DKK1 and RUNX2 in ACLT + MMx rats compared with the NS-treated ACLT + MMx group.
      The present study demonstrated that PTH 1-34 upregulated the Wnt/beta-catenin
      signaling pathway and that PTH1-34 downregulated RUNX2 through an alternative
      pathway to the Wnt/beta-catenin signaling pathway, in a rat model of OA.

PMID- 29039527
TI  - Simvastatin inhibits the expression of stemness-related genes and the metastatic
      invasion of human cancer cells via destruction of the cytoskeleton.
AB  - Statins are a class of drugs that inhibit the rate-limiting steps in the
      cholesterol biosynthesis pathway. They act by inhibiting 3-hydroxy-3
      methylglutaryl CoA (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA
      to mevalonate. Blocking of mevalonate synthesis leads to inhibition of the
      farnesylation and geranylgeranylation of several functional proteins, such as
      RhoA and other small guanosine triphosphate-binding proteins, that are important
      in maintaining the undifferentiated status of the cells. In the present study, we
      hypothesized that simvastatin, likely through the inhibition of farnesylation and
      geranylgeranylation of Rac1, Cd42 and RhoA, induces a destruction/restructuration
      of the cytoskeleton that decreases mechanical strain transfer to the nuclei,
      inducing the loss of transmission of regulatory signals from the cytoskeleton to
      the nucleoskeleton. Although this remains at present a hypothesis and is not easy
      to define if the de-structuration of the cytoskeleton is a secondary effect of
      simvastatin treatment or the inhibition of post-translational protein
      modification have a precise role in the structuration of actin cytoskeleton, we
      speculate that these signal variations could inhibit the expression of certain
      stemness genes, which could therefore be considered nucleoskeleton-associated and
      mechanically regulated genes. On the other hand, the restructuration of the
      cytoskeleton inhibits the formation of lamellipodia and filopodia, which likely
      decreases the capability of cancer cells to invade the extracellular matrix,
      thereby modulating the equilibrium between proliferation, differentiation and
      metastatic invasion in human cancer cells. On the basis of our results we think
      that simvastatin, alone or in combination with conventional drugs, may have a
      possible role in cancer therapy.

PMID- 29039528
TI  - lncRNA ROR promotes the proliferation of renal cancer and is negatively
      associated with favorable prognosis.
AB  - Renal cell carcinoma (RCC) is one of the third most common types of urological
      cancer worldwide. Long non-coding RNA (lncRNA) ROR has been reported to be
      important in regulating the malignant activities of different types of cancer,
      however, the function of lncRNA ROR in RCC remains to be fully elucidated. In
      order to investigate the function of lncRNA ROR in RCC, reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) analysis was used to detect the
      expression of lncRNA ROR in renal cancer tissues and adjacent tissues. Cell
      proliferation and apoptosis were determined using Cell Counting Kit-8 and
      apoptosis assays. Western blot analysis was used to measure the expression levels
      of c-Myc and p53 following the suppression of lncRNA ROR in RCC cell lines.
      According to the results of the RT-qPCR analysis, lncRNA ROR was found to be
      expressed at high levels in RCC tissues and cell lines. Patients with RCC
      exhibiting high expression levels of lncRNA ROR had shorter survival rates,
      compared with those with low expression levels of lncRNA ROR. The knockdown of
      lncRNA ROR resulted in a decrease of cell proliferation and increase of apoptosis
      in vitro. The suppression of lncRNA ROR also induced an increase in the
      expression of p53 and a decrease in the expression of c-Myc in vitro. Taken
      together, these results demonstrated that lncRNA ROR was expressed at high levels
      in RCC tissue and cell lines, and was associated with the proliferation ability
      of RCC cells. These findings indicate that lncRNA ROR may be a promising
      therapeutic target for treating RCC.

PMID- 29039529
TI  - Inhibitory effect of 1-tetradecanol on Helicobacter pylori-induced production of
      interleukin-8 and vascular endothelial growth factor in gastric epithelial cells.
AB  - Helicobacter pylori (H. pylori) infection activates pro-inflammatory mediators,
      including interleukin (IL)-8 and vascular endothelial growth factor (VEGF) in
      gastric epithelial cells. 1-Tetradecanol (1-TD) has been purified from
      Dendropanax morbifera Leveille; its physiological activities are poorly
      understood. The present study assessed whether 1-TD has an effect on H. pylori
      mediated inflammation in AGS gastric epithelial cells. 1-TD reduced IL-8
      production by AGS cells in response to H. pylori in a significant and dose
      dependent manner, as measured by ELISA. Western blot analysis demonstrated that 1
      TD also suppressed the activation of nuclear factor-kappaB, and two mitogen
      activated protein kinase species (p38 and extracellular signal-regulated kinase
      1/2), but not c-Jun N-terminal kinase in H. pylori-infected AGS cells. As
      predicted, VEGF expression and hypoxia inducible factor-1alpha stabilization
      induced by H. pylori in AGS cells were inhibited by 1-TD. In addition, 1-TD
      directly inhibited the growth of H. pylori in a dose-dependent manner, as
      investigated by measuring the optical density. These findings indicated that 1-TD
      may be a potential preventive or therapeutic agent for H. pylori-induced gastric
      inflammation.

PMID- 29039530
TI  - Hepatitis C virus p7 induces mitochondrial depolarization of isolated liver
      mitochondria.
AB  - Hepatitis C virus (HCV)-encoded protein p7 is a viroporin that acts as an ion
      channel and is indispensable for HCV particle production. Although the main
      target of HCV p7 is the endoplasmic reticulum, it also targets mitochondria. HCV
      infected cells show mitochondrial depolarization and ATP depletion; however, the
      function of HCV p7 in mitochondria is not fully understood. The present study
      demonstrated that treatment of isolated mouse liver mitochondria with the
      synthesized HCV p7 protein induced mitochondrial dysfunction. It also
      demonstrated that HCV p7 targeted isolated mouse liver mitochondria and induced
      mitochondrial depolarization. In addition, HCV p7 triggered matrix acidification
      and, ultimately, a decrease in ATP synthesis in isolated mitochondria. These
      findings indicate that targeting of mitochondria by HCV p7 in infected cells
      causes mitochondrial dysfunction to support HCV particle production. The present
      study provided evidence for the role of HCV p7 in mitochondria, and may lead to
      the development of novel strategies for HCV therapy.

PMID- 29039531
TI  - Prognostic implications and procoagulant activity of phosphatidylserine exposure
      of blood cells and microparticles in patients with atrial fibrillation treated
      with pulmonary vein isolation.
AB  - The present study aimed to evaluate the procoagulant effects of
      phosphatidylserine (PS) exposure on blood cells and microparticles (MPs), and
      examine its role in predicting early recurrence atrial fibrillation (ERAF) in
      patients with atrial fibrillation (AF) treated with pulmonary vein isolation
      (PVI). Blood samples were obtained from 40 healthy controls and 56 patients with
      AF at baseline (prior to PVI), and 0, 1 h, 1 day, 3 days and 7 days following
      PVI. The exposure of PS (PS+) to blood cells (platelets, erythrocytes and
      leukocytes) and MPs was detected using flow cytometry. The procoagulant activity
      was evaluated by coagulation time, and the formation of factor Xa (FXa) and
      thrombin. In addition, independent factors associated with PS+ blood cells and
      MPs, and significant predictors of ERAF following PVI were investigated by
      statistical analyses. The numbers of PS+ blood cells and MPs were significantly
      increased by PVI (P<0.01). A significant decrease in coagulation time, and
      increases in FXa and thrombin were exhibited in the PS+ blood cells and MPs from
      patients with AF treated with PVI, whereas these alterations were inhibited by
      either lactadherin or anti-tissue factor (P<0.01). The maximum power of the PVI
      was significantly associated with platelet-derived MPs, and high-sensitivity C
      reactive protein (hs-CRP) was closely associated with leukocyte-derived MPs and
      endothelial-derived MPs (EMPs) (P<0.01). In addition, hs-CRP and EMPs >355/ul
      were identified as independent predictors of ERAF (P<0.05). The increased numbers
      of PS+ platelets, erythrocytes, leukocytes and MPs contributed to the
      procoagulant state of AF, and hs-CRP and EMPs were able to predict ERAF following
      PVI.

PMID- 29039532
TI  - Puerarin attenuates the daunorubicin-induced apoptosis of H9c2 cells by
      activating the PI3K/Akt signaling pathway via the inhibition of Ca2+ influx.
AB  - Puerarin extracted from Radix Puerariae is well known for its pharmacological
      effects, including antioxidant, anti-inflammatory, neuroprotective and
      cardioprotective properties. In this study, we aimed to investigate the effects
      of puerarin on the daunorubicin (DNR)-induced apoptosis of H9c2 cells and to
      elucidate the potential mechanisms involved. MTT assay and flow cytometry were
      performed to evaluate cell cytotoxicity and apoptosis, respectively. Western blot
      analysis was used to assess changes in the expression levels of proteins,
      including caspase-3, Akt and phosphorylated Akt (p-Akt). Ratiometric imaging of
      intracellular calcium (Ca2+) using cells loaded with Fura-2 was also carried out.
      Our results revealed that puerarin pre-treatment protected the H9c2 cells against
      DNR-induced cytotoxicity by inhibiting cell apoptosis, which was also confirmed
      by the decrease in the expression of cleaved caspase-3. Additionally, p-Akt
      activation was associated with the suppressive effects of puerarin. Following pre
      treatment with puerarin, the extracellular Ca2+ influx was restrained and this
      resulted in a reduction in the intracellular Ca2+ levels; these effects were
      abrogated by LY294002 [an inhibitor of phosphatidylinositol 3-kinase (PI3K)]. The
      inhibition of Ca2+ influx suggested that the PI3K/Akt signaling pathway
      participated in the suppressive effects of puerarin against H9c2 cell apoptosis.
      Taken togher, our findings demonstrate that puerarin attenuates the DNR-induced
      apoptosis of H9c2 cells by activating the PI3K/Akt signaling pathway via the
      inhibition of Ca2+ influx, suggesting that puerarin may be a potential
      cardioprotective agent for use in the clinical treatment of cardiomyopathy
      triggered by DNR.

PMID- 29039533
TI  - SIRT1 activation by resveratrol reduces brain edema and neuronal apoptosis in an
      experimental rat subarachnoid hemorrhage model.
AB  - Early brain injury is considered to be a major risk that is related to the
      prognosis of subarachnoid hemorrhage (SAH). In SAH model rats, brain edema and
      apoptosis have been closely related with death rate and neurological function.
      Sirtuin 1 (SIRT1) was reported to be involved in apoptosis in cerebral ischemia
      and brain tumor formation through p53 deacetylation. The present study aimed to
      evaluate the role of SIRT1 in a rat endovascular perforation model of SAH. The
      SIRT1 activator resveratrol (RES) was administered 48 h prior to SAH induction
      and the SIRT1 inhibitor Sirtinol (SIR) was used to reverse the effects of RES on
      SIRT1 expression. Mortality rate, neurological function and brain water content
      were measured 24 h post-SAH induction. Proteins associated with the blood brain
      barrier (BBB), apoptosis and SIRT1 in the cortex, such as zona occludens 1 (ZO
      1), occludin, claudin-5, SIRT1, p53 and cleaved caspase3 were investigated. mRNA
      expression of the p53 downstream molecules including Bcl-associated X protein,
      P53 upregulated modulator of apoptosis, Noxa and BH3 interacting-domain death
      agonist were also investigated. Neuronal apoptosis was also investigated by
      immunofluorescence. RES pretreatment reduced the mortality rate and improved
      neurological function, which was consistent with reduced brain water content and
      neuronal apoptosis; these effects were partially reversed by co-treatment with
      SIR. SIRT1 may reduce the brain water content by improvement of dysfunctional BBB
      permeability, and protein analysis revealed that both ZO-1, occludin and claudin
      5 may be involved, and these effects were reversed by SIRT1 inhibition. SIRT1 may
      also affect apoptosis post-SAH through p53 deacetylation, and the analysis of p53
      related downstream pro-apoptotic molecules supported this hypothesis.
      Localization of neuron specific apoptosis revealed that SIRT1 may regulate
      neuronal apoptosis following SAH. SIRT1 may also ease brain edema and neuronal
      protection through BBB improvement and p53 deacetylation. SIRT1 activators such
      as RES may have the potential to improve the prognosis of patients with SAH and
      clinical research should be investigated further.

PMID- 29039534
TI  - Apurinic/apyrimidinic endonuclease 1 (APE1) contributes to resveratrol-induced
      neuroprotection against oxygen-glucose deprivation and re-oxygenation injury in
      HT22 cells: Involvement in reducing oxidative DNA damage.
AB  - Resveratrol, a naturally occurring polyphenolic compound, exhibits a
      neuroprotective role in models of central nervous system diseases, including
      cerebral ischemia/reperfusion injury. Apurinic/apyrimidinic endonuclease 1 (APE1)
      is a multifunctional enzyme that contributes to base excision repair of oxidative
      DNA damage and redox activation of transcription factors, associated with
      neuronal survival against hypoxic-ischemic injury. It was hypothesized that
      resveratrol protects HT22 cells against oxygen-glucose deprivation and re
      oxygenation (OGD/R)-induced injuries through upregulation of APE1. It was
      demonstrated that resveratrol pretreatment significantly increased the viability
      of HT22 cells and decreased the release of lactate dehydrogenase (LDH),
      accompanied by the upregulation of APE1 mRNA, and protein levels, as well as the
      activity of APE1 under OGD/R conditions. In addition, resveratrol reversed OGD/R
      induced oxidative DNA damage as evidenced by the decreases in the levels of 8
      hydroxy-2'-deoxyguanosine and APE sites. However, APE1 knockdown using short
      hairpin RNA sequence targeting APE1 abolished resveratrol-elicited beneficent
      effects against OGD/R-induced cytotoxicity and oxidative stress. This was
      indicated by decreased cell viability, superoxide dismutase activity and
      glutathione levels, and increased LDH release and reactive oxygen species levels.
      The results of the present study indicate that APE1 contributes to the protective
      effects of resveratrol against neonatal hypoxic-ischemic brain injuries, and
      suggest that DNA repair enzymes, including APE1, may be a unique strategy for
      neuroprotection against this disease.

PMID- 29039535
TI  - Clinical implications of progranulin in gastric cancer and its regulation via a
      positive feedback loop involving AKT and ERK signaling pathways.
AB  - In previous years, progranulin (PGRN) has attracted increasing attention due to
      its oncogenic roles in several types of tumor. However, the clinical relevance of
      PGRN in gastric cancer remains to be elucidated. In the present study, 120
      retrospective tissue samples were obtained from patients with primary gastric
      cancer, and the expression of PGRN was detected using immunohistochemistry. The
      results showed that 71 cases exhibited a high expression of PGRN, which was
      markedly higher than the 49 cases with a low expression of PGRN. Subsequent chi2
      analysis confirmed for the first time, to the best of our knowledge, that a high
      level of PGRN was positively correlated with lymph node metastasis (P=0.048),
      lymphatic invasion (P=0.018) and advanced clinical stage (P=0.027). Survival
      analysis showed that PGRN was positively correlated with poorer overall survival
      (OS; P=0.0043) and progression-free survival (PFS; P=0.0022). Univariate and
      multivariate Cox regression analysis showed that PGRN and clinical stage had a
      significant effect on the OS and PFS of the patients with gastric cancer. In
      addition, cell experiments confirmed that extracellular PGRN promoted the
      intracellular expression of PGRN in a concentration-dependent manner in gastric
      cancer cells. The AKT and extracellular signal-regulated kinase signaling
      pathways were involved in the upregulation of intracellular PGRN induced by
      extracellular PGRN in MKN-45 and MGC-803 gastric cancer cells. Taken together,
      the results of the present study suggested that PGRN may be important in the
      progression and prognosis of gastric cancer, and that the expression of PGRN was
      regulated in a positive feedback loop. These findings enhance current knowledge
      regarding PGRN in tumors.

PMID- 29039536
TI  - Adipose-derived mesenchymal stem cells attenuate cisplatin-induced apoptosis in
      epithelial ovarian cancer cells.
AB  - Environment-mediated drug resistance (EMDR) serves an important role in tumor
      chemotherapy resistance. Adipose-derived mesenchymal stem cells (ADSC) are an
      important component of the tumor microenvironment. However, the role of ADSC in
      EMDR remains unclear. Therefore, in order to clarify whether ADSCs contribute to
      the cisplatin-mediated apoptosis in epithelial ovarian cancer (EOC), the present
      study isolated ADSCs from the omentum of women with benign disease and collected
      the ADSC culture medium as conditioned medium. Subsequently, it was revealed that
      ADSCs decreased the sensitivity of EOC cells to cisplatin via an MTT assay. In
      addition, it was revealed that ADSCs may reduce cisplatin-induced apoptosis in
      EOC cells, as determined by Hoechst staining and flow cytometric analysis.
      Additionally, a lower level of cleaved caspase-3 was observed, accompanied with
      decreased intracellular platinum accumulation in EOC cells indirectly co-cultured
      with ADSCs. In conclusion, the findings of the present study suggested that ADSCs
      reduced cisplatin-induced apoptosis and the intracellular level of platinum in
      EOC cells, which in turn resulted in cisplatin resistance. Therefore, ADSCs may
      serve as a therapeutic target for recurrent EOC.

PMID- 29039537
TI  - Juglone potentiates TRAIL-induced apoptosis in human melanoma cells via
      activating the ROS-p38-p53 pathway.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-based cancer
      therapy offers promise as TRAIL can kill cancer cells without apparent toxicity
      towards normal cells. However, intrinsic or acquired resistance to TRAIL
      inseveral types of cancer cell has become a major challenge in TRAIL-based cancer
      therapy. Juglone is a natural compound isolated from walnut trees. In the present
      study, it was demonstrated that juglone sensitized melanoma cells to TRAIL
      induced cytotoxicity by MTT and crystal violet assays. Flow cytometry analysis
      indicated that juglone potentiated TRAIL-induced cell death. Western blot assay
      demonstrated that the expressions of cleaved poly(ADP-ribose) polymerase (PARP)
      and cleaved caspase 3 were markedly increased in the juglone combined with TRAIL
      group. Exposure to TRAIL alone did not induce the production of reactive oxygen
      species (ROS), activation of p38 orincrease of p53 in the TRAIL-resistant
      melanoma cells, as determined by flow cytometry and western blot analysis.
      However, exposure to TRAIL in combination with juglone markedly increased the
      production of ROS, activated p38 and increased p53, compared with the cells
      treated with either juglone or TRAIL alone. Pretreatment with N-acetyl cysteine,
      a ROS scavenger, significantly reduced the cytotoxicity of juglone in combination
      with TRAIL, which further supported that ROS was involved in the juglone-induced
      sensitization of TRAIL. In conclusion, juglone potentiated TRAIL-induced
      apoptosis in melanoma cells, and these effects were partially mediated through
      the ROS-p38-p53 pathway. These findings suggested that juglone may be a potential
      sensitizer for TRAIL therapy in the treatment of melanoma.

PMID- 29039538
TI  - Potential lncRNA diagnostic biomarkers for early gastric cancer.
AB  - Long noncoding RNAs (lncRNAs) serve important functions in many crucial
      biological processes; however, the effects of lncRNAs in early gastric cancer
      (EGC) are not entirely clear. The present study aimed to demonstrate the
      potential of lncRNAs to be used as biomarkers in EGC. Reverse transcription
      quantitative polymerase chain reaction was used to measure the expression levels
      of lncRNAs, including X inactive-specific transcript (XIST), Yiya, brain
      cytoplasmic RNA 1 (BCYRN1), ribosomal RNA processing 1B (RRP1B), KCNQ1 opposite
      transcript 1 (KCNQ1OT1) and testes development related 1 (TDRG1), in EGC tissues
      compared with normal adjacent tissues (NATs). XIST, BCYRN1, RRP1B and TDRG1 were
      identified as differentially expressed in EGC tissues compared with NATs. The
      specificity and sensitivity of XIST, BCYRN1, RRP1B and TDRG1 were determined by
      receiver operating characteristic curve analysis. In addition, RRP1B expression
      was revealed to be significantly correlated with distal metastasis (P=0.020) and
      tumor-node-metastasis staging (P=0.018), and TDRG1 expression was significantly
      correlated with lymph node metastasis (P=0.001). Furthermore, BCYRN1, RRP1B and
      TDRG1 expression levels were compared between EGC tissues and plasma, and the
      results indicated that there were significant positive correlations of XIST,
      BCYRN1, RRP1B and TDRG1 expression levels between the EGC tissues and plasma.
      Therefore, the present study suggested that XIST, BCYRN1, RRP1B and TDRG1 may be
      served as potential diagnostic biomarkers for EGC.

PMID- 29039539
TI  - Adenoviral-bone morphogenetic protein-7 and/or doxazosin therapies promote the
      reversion of fibrosis/cirrhosis in a cirrhotic hamster model.
AB  - Liver fibrosis occurs in the presence of continuous insults, including toxic or
      biological agents. Novel treatments must focus on ceasing the progression of
      cellular damage, promoting the regeneration of the parenchyma and inhibition of
      the fibrotic process. The present study analyzed the effect of bone morphogenetic
      protein (BMP)-7 gene therapy with or without co-treatment with doxazosin in a
      model of liver cirrhosis in hamsters. The serum alanine aminotransferase,
      aspartate aminotransferase and albumin levels were analyzed
      spectrophotometrically. Tissue hepatic samples were analyzed by hematoxylin and
      eosin for parenchymal structure and Sirius red for collagen fiber content. BMP-7
      and alpha-smooth muscle actin (SMA)-positive cells were detected by
      immunohistochemistry. BMP-7 and collagen type I content in hepatic tissue were
      analyzed by western blotting, and tissue inhibitor of metalloproteinases (TIMP)-2
      and matrix metalloproteinase (MMP)-13 expression levels were detected by reverse
      transcription-quantitative polymerase chain reaction. The present study detected
      a significant reduction of collagen type I deposits in the group treated with
      adenoviral-transduction with BMP-7 and doxazosin. In animals with BMP-7 and
      doxazosin therapy, alpha-SMA-positive cells were 31.7 and 29% significantly
      decreased compared with animals with placebo, respectively. Adenoviral-BMP-7
      transduction and/or doxazosin treatments actively induced decrement in type I
      collagen deposition via increased MMP-13 and reduced TIMP-2 expression. In
      conclusion, the adenovirus-BMP-7 gene therapy and the doxazosin therapy are
      potential candidates for the diminution of fibrosis in the liver, although
      combination of both therapies does not improve the individual anti-fibrotic
      effect once cirrhosis is established.

PMID- 29039540
TI  - Synthesis of regioselectively acylated quercetin analogues with improved
      antiplatelet activity.
AB  - The aim of the present study was to report on a complete synthetic approach,
      namely benzylation-hydrolysis-acylation-hydrogenation, to the synthesis of
      regioselectively acylated quercetin analogues using low-cost rutin as a starting
      material. Three quercetin analogues, quercetin-3-O-propionate (Q-pr), quercetin-3
      O-butyrate (Q-bu) and quercetin-3-O-valerate (Q-va), containing 3-, 4- and 5
      carbon aliphatic acyl chains, respectively, were synthesized and characterized
      with 1H nuclear magnetic resonance (NMR), 13C NMR and mass spectrometry. Compared
      with quercetin, all three analogues exhibited improved lipophilicity. The
      lipophilicity of the analogue increased with increasing acyl chain length. Q-va
      exhibited the highest lipophilicity among the three analogues, but a lower water
      solubility compared with quercetin. By contrast, Q-pr and Q-bu exhibited 8.2- and
      4.7-fold higher water solubility compared with quercetin, respectively. The in
      vitro and in vivo studies demonstrated that Q-pr and Q-bu were more effective
      whereas Q-va was less effective in inhibiting platelet aggregation compared with
      quercetin. These results indicated that the water solubility and the
      lipophilicity of the analogues must be improved in order to achieve higher
      antiplatelet activity, and an optimal acyl chain length is crucial for the
      synthesized quercetin analogues to be more effective.

PMID- 29039541
TI  - Modulation of mitogen-activated protein kinase attenuates sepsis-induced acute
      lung injury in acute respiratory distress syndrome rats.
AB  - Sepsis is the most important predisposing cause inducing acute respiratory
      distress syndrome (ARDS); however, the mechanism of sepsis leading to the
      development of ARDS remains to be elucidated. Suppression of the mitogen
      activated protein kinase (MAPK) signal by blocking the phosphorylation of Jun N
      terminal kinase (JNK) and p38 in lung tissues could alleviate acute lung injury
      induced by sepsis. MAPK signaling may have a crucial role in development of the
      sepsis-induced acute lung injury. The specific inhibitors of JNK and p38 MAPK,
      SP600125 and SB203580, were administrated by intragastric injection 4 h before
      induction of ARDS after cecal ligation and puncture (CLP). Rats were sacrificed
      at 1, 6 or 24 h after CLP challenge. The histological evaluation, lung water
      content, and biochemical analysis were performed. The results revealed that the
      JNK and p38 MAPK inhibitor improved lung permeability, attenuated system
      inflammation, further alleviated the lung injury induced by sepsis. In
      conclusion, JNK and p38 MAPK signaling are essential for the development of ARDS
      following sepsis. Further studies are needed to illuminate the detailed
      mechanisms of JNK and p38 MAPK signaling in sepsis-induced ARDS.

PMID- 29039542
TI  - Propofol regulates the expression of TLR4 through miR-21 in human umbilical vein
      endothelial cells.
AB  - Propofol (2,6-diisopropylphenol) is one of the most commonly used intravenous
      anesthetics. Anesthetics can regulate the inflammatory process; however, the
      mechanism remains to be fully elucidated. The present study aimed to investigate
      whether and how propofol affects the inflammatory reaction in human umbilical
      vein endothelial cells (HUVECs). The expression levels of Toll-like receptor 4
      (TLR4) and cluster of differentiation 14 (CD14) were determined in HUVECs treated
      with propofol and lipopolysaccharide (LPS) using western blot and reverse
      transcription-quantitative polymerase chain reaction analyses. In addition,
      whether propofol regulated the expression of TLR4 though microRNA (miR)-21 was
      examined. The results showed that LPS promoted the expression levels of TLR4,
      CD14 and tumor necrosis factor alpha (TNFalpha), and suppressed the expression of
      miR-21 in HUVECs. Propofol suppressed the expression levels of TLR4, CD14 and
      TNFalpha, and upregulated the expression of miR-21 in a concentration-dependent
      manner. miR-21 downregulated the expression of TLR4 at the mRNA and protein
      levels, whereas the miR-21 mimic reversed the effect of LPS on the expression of
      TLR4. In addition, the miR-21 inhibitor inhibited the downregulatory effect of
      propofol on the expression of TLR4. TargetScan analysis showed that TLR4 was
      included in the list of targets of miR-21. Fluorescent reporter assays showed
      that the miR-21 mimic and propofol treatment reduced the fluorescence intensity
      in cells transfected with a reporter vector containing the wild-type TLR4 3'
      untranslated region. Taken together, the results of the present study
      demonstrated that propofol regulated the expression of TLR4 in HUVECs through miR
      21.

PMID- 29039543
TI  - Oxidized low density lipoprotein facilitates tumor necrosis factor-alpha mediated
      chondrocyte death via autophagy pathway.
AB  - We aimed to investigate the role of oxidized low density lipoprotein (ox-LDL) in
      tumor necrosis factor-alpha (TNF-alpha) mediated chondrocyte death and explore
      the mechanisms. Ten osteoarthritis (OA) and normal control cartilage tissue and
      synovial fluid (SF) samples were collected, and the expression of lectin-like ox
      LDL receptor-1 (LOX-1) and ox-LDL level was examined by real time quantitative
      PCR and enzyme-linked immunosorbent assay (ELISA). An in vitro chondrocyte model
      was established by the introduction of TNF-alpha and ox-LDL, cell death was
      analyzed by trypan blue assay and the mechanisms were explored based on the
      apoptosis related pathway and autophagy pathway. Significantly increased ox-LDL
      level (70.30+/-17.83 vs. 37.22+/-19.97, P<0.05) in SF sample and LOX-1 expression
      level (0.51+/-0.10 vs. 0.32+/-0.04, P<0.05) in cartilage tissue was found in OA
      patients compared to those corresponding samples from control subjects. Ox-LDL
      could facilitate TNF-alpha mediated chondrocyte death and this effect could be
      blocked by LOX-1 antibody neutralization. Autophagy inhibition by 3-MA and Atg-5
      siRNA could reverse the cell death effect mediated by TNF-alpha and ox-LDL co
      treatment on chondrocytes. Oxidized low density lipoprotein facilitates tumor
      necrosis factor-alpha mediated chondrocyte death via its interaction with LOX-1,
      and autophagy is involved in the mechanisms.

PMID- 29039544
TI  - Formyl peptide receptor 2 expression predicts poor prognosis and promotes
      invasion and metastasis in epithelial ovarian cancer.
AB  - Formyl peptide receptor 2 (FPR2) has been identified as a member of the G protein
      coupled chemoattractant receptor (GPCR) family and has been implicated as playing
      a role in both inflammation and cancer development. Epithelial ovarian cancer
      (EOC) has been suggested to be correlated with both infectious and non-infectious
      inflammation. To date, the role of FPR2 in EOC remains poorly understood and
      controversial. In the present study, we aimed to investigate the potential of
      FPR2 in regulating EOC. We performed immunohistochemistry and RT-qPCR to analyzed
      expression of FPR2 in EOC tissues and the correlation between FPR2 and EOC
      clinicopathological characteristics as well as prognosis were also analyzed. To
      test the role of FPR2 in EOC cell migration, we established FPR2-knockdown SKOV3
      cells and performed wound-healing, Transwell and angiogenesis assays to detect
      the metastatic potential of these EOC cells. Our studies found that FPR2 was
      overexpressed in EOC tissues and was positively correlated with EOC
      clinicopathological characteristics including the International Federation of
      Gynecology and Obstetrics (FIGO) stage, histological grade and ovarian cancer
      type. Survival analyses suggested that FPR2 overexpression indicated the poorer
      prognosis of EOC patients and FPR2 may act as an independent risk factor for EOC
      prognosis. FPR2 knockdown decreased the migration potential of the ovarian cancer
      cells. Moreover, serum amyloid A (SAA) may stimulate the migration of SKOV3 cells
      through FPR2. The present study suggested that FPR2 promoted the invasion and
      metastasis of EOC and it could be a prognostic marker for EOC.

PMID- 29039545
TI  - Grape seed proanthocyanidins protect cardiomyocytes against hypoxia/reoxygenation
      injury by attenuating endoplasmic reticulum stress through PERK/eIF2alpha
      pathway.
AB  - The aim of the present study was to observe the protective effect of grape seed
      proanthocyanidins (GSPs) against endoplasmic reticulum (ER) stress-mediated
      apoptosis caused by hypoxia/reoxygenation (H/R) injury in H9C2 cardiomyocytes
      along with its potential mechanisms. H9C2 cardiomyocytes underwent hypoxia for 3
      h followed by reoxygenation for 3 h. Different doses of GSPs (50, 100 and 200
      ug/ml) were administered 30 min before hypoxia. Cell viability was assessed, as
      well as lactic dehydrogenase (LDH) activity, cell apoptosis rate, expression
      levels of glucose-regulated protein 78 (GRP78), C/EBP-homologous protein (CHOP),
      protein kinase RNA-like ER kinase (PERK), and eukaryotic translation initiation
      factor-2 (eIF2alpha) mRNA and protein. The results revealed that GSPs improved
      cell viability, reduced LDH activity and reduced the apoptosis rate in cells
      subjected to H/R, and that the protective effect was most significant when 100
      ug/ml in GSPs was administered. GSPs treatment also decreased mRNA and protein
      expression of GRP78, CHOP, eIF2alpha and the level of the phosphorylated form of
      PERK. Furthermore, GSPs displayed a similar protective effect to that of
      established ER stress inhibitor 4-phenyl butyric acid. In conclusion, the
      findings of this study suggest that GSPs may protect H9C2 cardiomyocytes from H/R
      injury by decreasing ER stress-mediated apoptosis through the suppression of the
      PERK/eIF2alpha signaling pathway.

PMID- 29039546
TI  - Antiproliferative effects of TSA, PXD-101 and MS-275 in A2780 and MCF7 cells:
      Acetylated histone H4 and acetylated tubulin as markers for HDACi potency and
      selectivity.
AB  - Inhibition of histone deacetylase enzymes (HDACs) has been well documented as an
      attractive target for the development of chemotherapeutic drugs. The present
      study investigated the effects of two prototype hydroxamic acid HDAC inhibitors,
      namely Trichostatin A (TSA) and Belinostat (PXD-101) and the benzamide Entinostat
      (MS-275) in A2780 ovarian carcinoma and MCF7 breast adenocarcinoma cells. The
      three HDACi inhibited the proliferation of A2780 and MCF7 cells at comparable
      levels, below the uM range. Enzyme inhibition assays in a cell-free system showed
      that TSA was the most potent inhibitor of total HDAC enzyme activity followed by
      PXD-101 and MS-275. Incubation of A2780 and MCF7 cells with the hydroxamates TSA
      and PXD-101 for 24 h resulted in a dramatic increase of acetylated tubulin
      induction (up to 30-fold for TSA). In contrast to acetylated tubulin, western
      blot analysis and flow cytometry indicated that the induction of acetylated
      histone H4 was considerably smaller. The benzamide MS-275 exhibited nearly a 2
      fold induction of acetylated histone H4 and an even smaller induction of
      acetylated tubulin in A2780 and MCF7 cells. Taken together, these data suggest
      that although the three HDACi were equipotent in inhibiting proliferation of MCF7
      and A2780 cells, only the benzamide MS-275 did not induce acetylated tubulin
      expression, a marker of class IIb HDACs.

PMID- 29039547
TI  - Frequency and distribution of CD4+CXCR5+ follicular B helper T cells within
      involved tissues in IgG4-related ophthalmic disease.
AB  - Immonoglobulin G4-related ophthalmic disease (IgG4-ROD) is a IgG4-RD and exhibits
      two main characteristics: Fibrosis that is not necessarily marked
      histopathologically; and frequent formation of germinal centers (GCs). Follicular
      B helper T (Tfh) cells are now recognized as the true helper cells for B cells in
      antibody responses. In the present study, the profile and distribution of Tfh
      cells in involved tissues from patients with IgG4-ROD was compared to those of
      type 1 autoimmune pancreatitis (AIP) and patients with IgG4-related
      lymphadenopathy (IgG4-RL). A total of 7 patients with IgG4-ROD, 7 patients with
      type 1 AIP or IgG4-RL and 7 IgG4-negative controls were evaluated. The expression
      of Tfh-cell immunological proteins, the inducible T-cell costimulator, B-cell
      lymphoma 6 protein, C-X-C chemokine receptor type 5 (CXCR5) and interleukin-21
      (IL-21) in affected tissues was analyzed using immunohistochemical staining and
      dual immunofluorescence. It was demonstrated that patients with IgG4-RD exhibited
      a significantly increased number of CD4+CXCR5+ Tfh cells compared with the IgG4
      negative controls. Furthermore, CD4+CXCR5+ Tfh cells were detected in and outside
      of GCs in patients with IgG4-ROD and IgG4-RLF, whereas CD4+CXCR5+ Tfh cells were
      randomly distributed in areas demonstrating type 1 AIP. Fewer CD4+CXCR5+ Tfh
      cells were observed in patients with type 1 AIP compared with patients with IgG4
      ROD and IgG4-RL. In addition, increased expression of IL-21 was observed in
      patients with IgG4-ROD and IgG4-RL compared with type 1 AIP. IL-21 expression was
      positively correlated with the IgG4/IgG ratio in immunohistochemically-positive
      cells. The results of the present study indicate that Tfh cells are involved in
      the histopathological pathogenesis of IgG4-RD and may serve a different role in
      IgG4-ROD and type 1 AIP. Tfh cells may serve a direct role in the IL-21-mediated
      pathogenesis of IgG4-ROD.

PMID- 29039548
TI  - [Corrigendum] Farnesoid X receptor deletion improves cardiac function, structure
      and remodeling following myocardial infarction in mice.
AB  - Following the publication of this article, an interested reader drew to our
      attention that we had incorrectly reported (in the Materials and methods section,
      'Western blot analysis', on p. 674) that the anti-farnesoid X receptor (FXR)
      antibody of Cell Signalling Technology, Inc., cat. no. #12295, had been used in
      this study to probe for FXR. In fact, the antibodies used in the above-mentioned
      study were a gift from the group of Dr Xin-Liang Ma at Thomas Jefferson
      University (Philadelphia, PA, USA), as referenced in the following article: [Pul
      J, Yuan A, Shan P, Gao E, Wang X, Wang Y, Lau WB, Koch W, Xin-Ma XL and He B:
      Cardiomyocyte-expressed farnesoid-X-receptor is a novel apoptosis mediator and
      contributes to myocardial ischaemia/reperfusion injury. Eur Heart J 34: 1834
      1845, 2013]. The antibody that was used for the western blotting analysis was
      raised against the C-terminus of FXR (C-20; cat. no. sc-1204, Santa Cruz
      Biotechnology, San Diego, CA, USA). We sincerely apologize for this mistake, and
      thank the reader of our article who drew this matter to our attention. The error
      made in our incorrect referencing of the antibody did not affect the conclusions
      reported in this study. Furthermore, we regret the inconvenience that this
      mistake caused. [the original article was published in the Molecular Medicine
      Reports 16: 673-679, 2017; DOI: 10.3892/mmr.2017.6643].

PMID- 29039549
TI  - Downregulation of caspase-3 alleviates Mycoplasma pneumoniae-induced apoptosis in
      alveolar epithelial cells.
AB  - Mycoplasma pneumoniae (M. pneumoniae) infection is closely associated with
      pneumonia in children. Apoptosis of alveolar epithelial cells is involved in the
      development of pneumonia in children. The present study aimed to examine how
      caspase-3 influences apoptosis rates in M. pneumoniae-infected alveolar
      epithelial cells. A549 alveolar epithelial cells were treated with M. pneumoniae,
      and cells and culture supernatant were collected at different time points.
      Alterations in apoptosis rates and caspase-3 mRNA and protein levels were
      measured for each treatment group. Cell apoptosis was detected using flow
      cytometry and TUNEL assay, and cell proliferation was detected using Cell
      Counting Kit-8 assay. Caspase-3 expression in A549 cells was inhibited via small
      interfering RNA (siRNA) knockdown and relative alterations in mRNA and protein
      levels and apoptosis rates were measured. Cytokine levels were measured using
      ELISA assay. Apoptosis rates of alveolar epithelial cells increased with
      prolonged exposure to M. pneumoniae (P<0.05). M. pneumoniae infection increased
      interleukin (IL)-4, IL-6 and IL-13 levels and reduced IL-10 levels. Caspase-3 was
      upregulated, whereas B cell lymphoma (Bcl)-2 was downregulated upon M. pneumoniae
      exposure for 24 h (P<0.05). Following 12 and 24 h of treatment, caspase-3 levels
      in the siRNA-treated cells were decreased compared with control group (P<0.05).
      M. pneumoniae also significantly altered caspase-3 and Bcl-2 protein expression.
      M. pneumoniae promoted apoptosis in alveolar epithelial cells via activation of
      the external death receptor pathway. Therefore, M. pneumoniae infection may
      affect the development of pneumonia in children by regulating caspase-3
      expression and promoting apoptosis.

PMID- 29039550
TI  - Autophagy is essential for flavopiridol-induced cytotoxicity against MCF-7 breast
      cancer cells.
AB  - Flavopiridol (FP) exerts antitumoral effects by triggering tumor cell cycle
      arrest and cytotoxicity in human breast cancer cell lines. The potent antitumor
      activity of FP is through its inhibition of cyclin-dependent kinases; however,
      this may not be the only mechanism of action. The present study aimed to
      investigate whether FP is able to induce autophagy and to examine the effects of
      autophagy on cell death in FP-treated MCF-7 human breast cancer cells. MCF-7
      cells were treated with either FP alone or FP in combination with chloroquine
      (CQ). Expression levels of autophagy-related protein LC3B-II and p62/sequestosome
      1 (SQSTM1) were used to monitor autophagic flux. MCF-7 cells were transfected
      with autophagy-related 5 (ATG5) small interfering (si)RNA to block autophagy.
      Cell viability and cell cycle status were determined. Following incubation with
      FP, MCF-7 cells exhibited significantly higher autophagy compared with untreated
      control cells, and the level of autophagy is comparable with cells under
      rapamycin induction, which was verified by immunodetection of LC3B-II and
      p62/SQSTM1 expression and inhibition by CQ. The addition of CQ treatment or ATG5
      siRNA transfection against autophagy components attenuated the cytotoxic effects
      of FP treatment of MCF-7 cells. Furthermore, this autophagy inhibition did not
      impair the FP-induced cell cycle arrest. These results revealed that autophagy
      may be involved in FP-induced MCF-7 cell death and autophagy inhibition enhanced
      the tumor cell pro-survival ability. It is possibly that potential autophagy
      regulatory drugs may be used as a chemotherapy adjuvant.

PMID- 29039551
TI  - Upregulation of Rho7 in the temporal lobe tissue of humans with intractable
      epilepsy.
AB  - Patients with intractable epilepsy (IE) exhibit an increased risk of premature
      death, psychosocial dysfunction and decreasing quality of life. The present study
      aimed to investigate the alteration in the expression of Rho7 in brain tissue
      from patients with IE, and to examine the association between Rho7 protein
      expression and IE. Temporal lobe samples were collected from the temporal lobes
      of 33 patients with IE patients and 10 age- and gender-matched histologically
      healthy controls. Immunohistochemical staining was conducted to assess the number
      of Rho7-positive cells. In addition, double-label immunofluorescent staining was
      performed to examine the cellular localization of Rho7. The protein expression of
      Rho7 was examined using western blotting. Marked immunoreactivity for Rho7 was
      detected in the IE group, while faint and scattered immunoreactive staining was
      observed in the control group. The count of Rho7 positive cells in the IE
      patients was significantly increased compared with the control subjects (23.47+/
      3.9% vs. 12.09+/-1.05%; P<0.01). Double-label immunofluorescent staining
      indicated that Rho7 was primarily expressed in the cell membrane and cytoplasm,
      and colocalized with neuron-specific enolase. Western blot analysis demonstrated
      that the expression of Rho7 in the IE group was significantly increased compared
      with the control group (0.41+/-0.031 vs. 0.25+/-0.025; P<0.01). The results of
      the present study demonstrated that upregulation of Rho7 immunoreactivity occurs
      in the brains of patients with IE, suggesting that Rho7 may be associated with
      the progression of IE or act as a potential treatment target.

PMID- 29039552
TI  - Prospective lncRNA-miRNA-mRNA regulatory network of long non-coding RNA LINC00968
      in non-small cell lung cancer A549 cells: A miRNA microarray and bioinformatics
      investigation.
AB  - Accumulating evidence suggests that the dysregulation of long non-coding RNAs
      (lncRNAs) serves vital roles in the incidence and progression of lung cancer.
      However, the molecular mechanisms of LINC00968, a recently identified lncRNA,
      remain unknown. The objective of present study was to investigate the role of a
      prospective lncRNA-miRNA-mRNA network regulated by LINC00968 in non-small cell
      lung cancer cells. Following the transfection of lentiviruses carrying LINC00968
      into A549 cells, the microRNA (miRNA) expression profile of the cells in response
      to the overexpression of LINC00968 was detected using an miRNA microarray. Five
      differentially expressed miRNAs (DEMs) with LINC00968 overexpression were
      obtained, including miR-9-3p, miR-22-5p, miR-668-3p, miR-3675-3p and miR-4536-3p.
      Five target prediction algorithms and three target validation algorithms were
      used to obtain 1,888 prospective target genes of the five DEMs. The result of
      Gene Ontology analysis suggested that these five DEMs were involved in complex
      cellular pathways, which included intracellular transport, organelle lumen and
      nucleotide binding. Furthermore, analysis of Kyoto Encyclopedia of Genes and
      Genomes pathways indicated that the five DEMs were important regulators in the
      adherens junction and focal adhesion. An lncRNA-miRNA-mRNA regulatory network and
      a protein-protein interaction network were then constructed. Eventually, a
      prospective lncRNA-miRNA-mRNA regulatory network of LINC00968, three miRNAs (miR
      9, miR-22 and miR-4536) and two genes (polo-like kinase 1 and exportin-1) was
      obtained following validation in the Cancer Genome Atlas database. These results
      may provide novel insights to support future research into lncRNA in lung cancer.

PMID- 29039553
TI  - Proteomic analysis of serum deprivation in tongue squamous cell carcinoma.
AB  - The occurrence of tongue squamous cell carcinoma (TSCC) is closely correlated
      with serum components; however, the detailed mechanism remains to be fully
      elucidated. Proteomic analysis contributed to the discovery of potential
      biomarkers and provided an insight into TSCC at a molecular level. The present
      study investigated the effect of serum deprivation on the Tca-8113 TSCC cell line
      through protein profiling using two-dimensional gel electrophoresis and mass
      spectrometry, with the aim of improving TSCC diagnosis. The results showed that
      the Tca-8113 cells maintained proliferative capacity and resisted apoptosis
      following serum deprivation. A total of 43 proteins were upregulated and 45 were
      downregulated following serum deprivation for 24 h, compared with untreated
      controls (0 h). The upregulated caspase-7, heat shock protein 27 and Annexin A1,
      and the downregulated peroxiredoxin-6 and heat shock protein 70, were selected
      for verification using reverse transcription-polymerase chain reaction analysis
      following serum deprivation for 16 h. The results indicated that reactive oxygen
      species may be important in serum deprivation-induced oxidative stress.

PMID- 29039554
TI  - MicroRNA-23a-3p inhibitor decreases osteonecrosis incidence in a rat model.
AB  - The mechanism of steroid-associated femoral head necrosis remains unclear. The
      present study investigated the role of microRNA-23a-3p (miR-23a-3p) in the
      incidence of osteonecrosis in a rat model. An miR-23a-3p mimic, an inhibitor and
      a negative control were transfected into bone mesenchymal stem cells using a
      lentiviral vector, and then injected into the steroid-induced femoral head
      necrosis model. Osteonecrosis incidence was assessed by micro computed tomography
      and histopathology. Low-density lipoprotein receptor-related protein 5 (LRP-5)
      expression was assessed by immunohistochemistry. The results demonstrated the
      incidence of osteonecrosis decreased in the miR-23a-3p inhibitor group compared
      with the miR-23a-3p mimic group (18.2% vs. 75%; P<0.05). The ratio of bone
      volume/total volume and trabecular thickness were significantly increased in the
      miR-23a-3p inhibitor group compared with the miR-23a mimic group. The expression
      level of LRP-5 was higher in the miR-23a-3p inhibitor group. The present study
      indicated that miR may provide a novel and alternative approach for understanding
      the mechanism underlying steroid-associated necrosis of the femoral head.

PMID- 29039555
TI  - miR-363 inhibits the growth, migration and invasion of hepatocellular carcinoma
      cells by regulating E2F3.
AB  - A growing body of evidence suggests that microRNA-363 (miR-363) plays crucial
      roles in tumor progression, development and metastasis, and confer resistance to
      chemotherapeutic drugs in several types of cancers. However, the biological
      function and underlying molecular mechanism of miR-363 in hepatocellular
      carcinoma (HCC) have not been fully elucidated. In the present study, we
      investigated the biological function and mechanism of miR-363 in the regulation
      of HCC progression. We found that miR-363 was downregulated in HCC cell lines and
      tissues, and a low expression level of miR-363 was associated with tumor
      differentiation, TNM stage and lymph node metastasis. Forced overexpression of
      miR-363 significantly suppressed HCC cell proliferation, migration, invasion and
      decreased epithelial-mesenchymal transition (EMT) in vitro, as well as inhibited
      tumor growth in vivo. Analysis of the underlying mechanisms revealed that miR-363
      regulated E2F transcription factor 3 (E2F3) expression by directly targeting its
      3' untranslated region. E2F3 overexpression partially attenuated the tumor
      suppressive effects of miR-363 in HCC cells. In addition, E2F3 expression was
      upregulated in the HCC tissues, and was negatively correlated with the level of
      miR-363 in human HCC tissues. Taken together, these results revealed that miR-363
      is involved in HCC growth and invasion and functions as a tumor suppressor by
      negatively regulating E2F3.

PMID- 29039556
TI  - Huaier extract enhances the treatment efficacy of paclitaxel in breast cancer
      cells via the NF-kappaB/IkappaBalpha pathway.
AB  - Breast cancer is considered as the most common malignant disease in women. Huaier
      extract, a type of traditional Chinese medicine, has been found to have antitumor
      activity. In the present study, we aimed to investigate whether the combined
      treatments of paclitaxel and Huaier extract may improve treatment efficacy in
      breast cancer cells. Human breast cancer cell lines MCF-7 and MDA-MB-231 were
      used to evaluate the antitumor efficacy of Huaier extract and paclitaxel both in
      vitro and in vivo. Using proliferation assays and flow cytometry, we found that
      both Huaier extract and paclitaxel decreased cell viability and induced cell
      apoptosis in a time- and dose-dependent manner. The combined treatments were more
      effective than monotherapy. Huaier extract induced cycle arrest in the G0/G1
      phase, and paclitaxel arrested the cell cycle in the G2/M phase. Furthermore, the
      results of real-time PCR and western blotting revealed that Huaier extract
      decreased p65 and c-Met expression and increased IkappaBalpha expression, while
      paclitaxel increased p65 expression and reduced IkappaBalpha and c-Met
      expression. Consistent with the in vitro results, both Huaier extract and
      paclitaxel exerted a significant inhibitory effect on xenografted tumor growth,
      and the combined therapies revealed the most marked inhibitory effect.
      Collectively, our results indicated that Huaier extract increased the antitumor
      effect of paclitaxel therapy in breast cancer cells. The molecular mechanisms may
      be involved in the inhibition of the NF-kappaB pathway and c-Met expression.

PMID- 29039557
TI  - MicroRNA-663 suppresses the proliferation and invasion of colorectal cancer cells
      by directly targeting FSCN1.
AB  - Colorectal cancer (CRC) is the most frequently diagnosed malignancy of the
      gastrointestinal tract. The dysregulation of microRNAs (miRNAs/miRs) has been
      reported in the majority of types of human cancer, and is correlated with
      tumorigenesis and tumor development. Abnormal expression of miR-663 has been
      observed in various types of human cancer. However, little is known about its
      role in CRC. Therefore, the aim of the present study was to clarify the
      expression and potential role of miR-663, and its underlying molecular mechanism
      in CRC. It was observed that miR-663 was markedly downregulated in CRC tissues
      and cell lines. Decreased miR-663 expression levels in CRC tissues were
      correlated with tumor, node, metastasis stage and lymph node metastasis.
      Functional assays revealed that upregulation of miR-663 inhibited cell
      proliferation and invasion in CRC. Further molecular mechanism assays
      demonstrated the fascin (FSCN1) was a target gene of miR-663. In addition, FSCN1
      was increased and negatively correlated with miR-663 expression in CRC tissues.
      FSCN1 underexpression mimicked the tumor suppressive functions induced by miR-663
      overexpression on CRC cell proliferation and invasion. Collectively, the present
      study presented evidence that miR-663 may act as a tumor suppressor in CRC by
      directly targeting FSCN1, which may lead to a potential therapeutic strategy
      focusing on miR-663 and FSCN1 for patients with this disease.

PMID- 29039558
TI  - Insulin in combination with cisplatin induces the apoptosis of ovarian cancer
      cells via p53 and JNK activation.
AB  - Drug resistance is an obstacle to effective treatment of ovarian cancer. There
      have been substantial evidences supporting the association between diabetes and
      the sensitivity to chemotherapy. Insulin (INS) is believed to be the strongest,
      most lasting hypoglycemic drug. Therefore, the present study aimed to elucidate
      whether insulin could facilitate the anti-proliferative activities of cisplatin
      (cis-diamminedichloroplatinum, DDP) in the A2780 ovarian cancer cell line. The
      inhibitory effects of DPP with/without INS on the growth of A2780 cells was
      measured by MTT assay. The cell cycle stages and levels of apoptosis were
      determined by flow cytometry. The amounts of signaling elements involved in the
      regulation of were examined using western blotting and reverse transcription
      quantitative polymerase chain reaction analysis. The results indicated that INS
      pre-treatment enhanced the inhibitory effect of DDP on the proliferation of A2780
      cells, and facilitated the apoptosis induced by DDP. INS-DDP treatment led to a
      marked decrease in the percentage of G0/G1 phase cells, but a corresponding
      increase in the proportion of S phase cells. Furthermore, A2780 cells pretreated
      with INS followed by DDP upregulated the protein expression level of
      phosphorylated c-Jun N-terminal kinase (JNK), which resulted in a substantial
      increase in the expression levels of p53 mRNA and protein, compared with DDP
      administration alone. In conclusion, the combination of INS and DDP facilitated
      the apoptosis of A2780 cells, which may be associated with the activation of the
      JNK signaling pathway and consequently the involvement of p53 at both mRNA and
      protein expression levels. These results may be useful in furthering our
      understanding of the mechanisms involved in the chemotherapeutic treatment of
      ovarian cancer.

PMID- 29039559
TI  - Matrine in association with FD-2 stimulates F508del-cystic fibrosis transmembrane
      conductance regulator activity in the presence of corrector VX809.
AB  - Cystic fibrosis is caused by mutations of the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene, and the predominant mutation is termed
      Phe508del (F508del). Therapy for F508del-CFTR patients is based on the use of
      Orkambi(r), a combination of VX809 and VX770. However, though Orkambi leads to an
      improvement in the lung function of patients, a progressive reduction in its
      efficacy has been observed. In order to overcome this effect, the aim of the
      present study was to investigate the role of matrine and the in-house compound FD
      2 in increasing the action of VX809 and VX770. Fischer rat thyroid cells
      overexpressing F508del-CFTR were treated with matrine, VX809 (corrector) and/or
      with a number of potentiators (VX770, FD-1 and FD-2). The results demonstrated
      that matrine was able to stimulate CFTR activity and, in association with FD-2,
      increased the functionality of the channel in the presence of VX809. Based on
      these results, it may be hypothesized that FD-2 may be a novel and more effective
      potentiator compared with VX770.

PMID- 29039560
TI  - 20-Hydroxyeicosatetraenoic acid regulates the expression of Nedd4-2 in kidney and
      liver through a neddylation modification pathway.
AB  - The present study aimed to test whether 20-hydroxyeicosatetraenoic acid (20-HETE)
      affected neddylation modification of E3-ligase Nedd4-2 (neural precursor cell
      expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase). A
      cytochrome P450 family 4 subfamily F member 2 (CYP4F2) transgenic mouse model
      that overproduces 20-HETE in the kidney and the liver was used in the present
      study. Transgenic mice with high salt intake exhibited increased activation of
      Nedd4-2-mediated ubiquitin-proteasome pathway. Nedd4-2 expression is increased in
      the kidney and decreased in the liver of transgenic mice compared with wild-type
      mice. Subsequently, co-immunoprecipitation analysis indicated that Nedd4-2 was
      modified by Nedd8, and the level of neddylation on Nedd4-2 was reduced in the
      kidney and increased in the liver of transgenic mice compared with controls. In
      addition, sentrin-specific protease 8 (Senp8), a deneddylation enzyme, is
      expressed higher in the kidney and lower in the liver of transgenic mice compared
      with wild-type controls. The function of 20-HETE on modulation of Nedd4-2 were
      also confirmed in mouse M1 kidney and mouse NCTC1469 liver cell lines, and the
      function was restored by neddylation inhibitor MLN4924 Data from the present
      study demonstrated that 20-HETE upregulated the expression of Nedd4-2 in the
      kidney and downregulated expression in the liver through the neddylation
      modification pathway, at least partly, depending on the effects on Senp8
      deneddylation.

PMID- 29039561
TI  - Hovenia dulcis Thunb. and its active compound ampelopsin inhibit angiogenesis
      through suppression of VEGFR2 signaling and HIF-1alpha expression.
AB  - Specific inhibition of angiogenesis has been considered a powerful strategy for
      the treatment of cancer and other angiogenesis-related human diseases. Hovenia
      dulcis Thunb., Japanese raisin tree or Oriental raisin tree, is a hardy tree
      found in Asia, Eastern China and Korea and has been known to possess various
      biological activities, including antifatigue, antidiabetic, neuroprotective and
      hepatoprotective activity. In the present study, for the first time, we evaluated
      whether a 100% ethanol extract of Hovenia dulcis Thunb. (HDT) inhibits the
      angiogenesis of human umbilical vein endothelial cells (HUVECs) using in vitro
      angiogenesis assays. HDT suppressed vascular endothelial growth factor (VEGF)
      induced proliferation, migration, invasion and tube formation of HUVECs at
      subtoxic doses. In addition, HDT significantly inhibited in vivo angiogenesis of
      the chorioallantoic membrane from growing chick embryos without exhibiting
      cytotoxicity. Furthermore, HDT downregulated not only VEGF receptor 2 (VEGFR2)
      signaling in HUVECs, but also hypoxia-inducible factor (HIF)-1alpha expression in
      hepatocarcinoma cell line HepG2. Ampelopsin is a bioactive flavanonol found in
      Hovenia dulcis Thunb. Our data showed that ampelopsin inhibited angiogenesis with
      no cytotoxicity by suppressing both VEGFR2 signaling and HIF-1alpha expression.
      These results suggest that Hovenia dulcis Thunb. and its active compound
      ampelopsin exhibit potent antiangiogenic activities and therefore could be
      valuable for the prevention and treatment of angiogenesis-related diseases
      including cancer.

PMID- 29039562
TI  - Downregulation of ZNF278 arrests the cell cycle and decreases the proliferation
      of colorectal cancer cells via inhibition of the ERK/MAPK pathway.
AB  - Zinc finger protein 278 is a zinc finger transcription factor encoded on the
      22q12.2 chromosome. Previous studies revealed that ZNF278 expression was
      significantly upregulated in colorectal cancer (CRC) tissue compared to adjacent
      non-tumor tissue. However, the expression and specific roles of ZNF278 in CRC
      remain unknown. ZNF278 expression was knocked down using specific siRNAs, which
      was confirmed by western blotting, and the effects of ZNF278 siRNAs on CRC cell
      proliferation were investigated. In addition, the effects of ZNF278
      overexpression were confirmed by western blotting and cell proliferation assay.
      Correlations between ZNF278 and the ERK/MAPK pathway were also detected by
      western blotting. We found that ZNF278 knockdown significantly induced cell cycle
      arrest, resulting in cyclin D1/E1 downregulation and p21 upregulation. Moreover,
      we demonstrated that downregulation of ZNF278 decreased the proliferation of CRC
      cells via inhibition of the extracellular signal-regulated kinase/mitogen
      activated protein kinase (ERK/MAPK) pathway for the first time. In conclusion,
      ZNF278 played a prominent role in the pathogenesis of CRC, and promoted CRC cell
      proliferation via the ERK/MAPK pathway, suggesting that it may act as a potential
      target in the diagnosis or treatment of CRC.

PMID- 29039563
TI  - Inhibition of human lung cancer proliferation through targeting stromal
      fibroblasts by dihydromyricetin.
AB  - In the present study, the effects of dihydromyricetin on the proliferative
      potential of fibroblasts and lung carcinoma cells were investigated. Markedly
      higher expression levels of smooth muscle actin and platelet derived growth
      factors (PDGFs) were observed in the fibroblasts using reverse transcription
      polymerase chain reaction analysis. The expression levels of PDGF-A and PDGF-B
      were also higher in the lung cancer cells. Western blot analysis revealed higher
      expression levels of the receptor for platelet-derived growth factor (PDGFRbeta)
      in the lysates from fibroblasts obtained from normal tissues and carcinoma
      tissues. Treatment of the fibroblasts with dihydromyricetin inhibited the
      expression of PDGFRbeta when treated with a 10 uM concentration for 48 h.
      Treatment of the fibroblasts with a 10 uM concentration of dihydromyricetin for
      48 h led to complete inhibition of the activation of extracellular signal
      regulated kinase (Erk)1/2 and Akt. The results of an MTT assay showed that
      treatment of the fibroblasts with dihydromyricetin significantly reduced the PDGF
      mediated increase in the rate of proliferation. The rate of proliferation of the
      A549 lung cancer cells cultured with fibroblasts was markedly increased, compared
      with that of the A549 cells cultured alone. However, dihydromyricetin
      significantly (P<0.05) inhibited the proliferation rate of the A549 cells
      cultured with fibroblasts, compared with the untreated cultures. The
      proliferation rates of the A549 cancer cells, A549 cells cultured with
      fibroblasts, and A549 cells cultured with fibroblasts and treated with
      dihydromyricetin were found to be were 78.45, 98.45 and 21.37%, respectively.
      Dihydromyricetin inhibited the proliferative potential of fibroblasts in the lung
      cancer cells through targeting the activation of Erk1/2 and Akt. Therefore, there
      is scope for dihydromyricetin to be evaluated further for the treatment of lung
      cancer.

PMID- 29039564
TI  - Evaluation of microRNA-203 in bone metastasis of patients with non-small cell
      lung cancer through TGF-beta/SMAD2 expression.
AB  - This study investigated the regulatory effect of microRNA-203 on bone metastasis
      of non-small cell lung cancer (NSCLC). Quantitative real-time PCR was used to
      examine microRNA-203 in tissue specimens of bone metastasis of patients with
      NSCLC. In bone metastasis of patients with NSCLC, microRNA-203 expression was
      decreased, compared with control group. We also surveyed overall survival (OS)
      and disease-free survival (DFS), microRNA-203 high expression in bone metastasis
      of patients with NSCLC was higher than in those with microRNA-203 low expression.
      Furthermore, we overexpressed microRNA-203 with microRNA-203 mimics and observed
      the effects of microRNA-203 overexpression on cell proliferation, apoptosis and
      migration of NSCLC cells. We found that microRNA-203 overexpression reduced cell
      proliferation and migration, induced apoptosis, Bax, caspase-3 and p53 protein
      expressions, repressed p-SMAD2 and TGF-beta1 protein expression of NSCLC cells.
      Knockdown of TGF-beta1 by LY364947 (10 nM) reduced cell proliferation and
      migration, induced apoptosis, expression of Bax, caspase-3 and p53 protein and
      suppressed TGF-beta1 and p-SMAD2 protein expression of NSCLC cells transfected
      with miR-124 mimics. In conclusion, our data suggest that microRNA-203/TGF
      beta/SMAD2 expression plays an important role as a tumor suppressor gene in bone
      metastasis of patients with NSCLC, and may reveal novel perspectives for clinical
      treatments against bone metastasis of patients with NSCLC.

PMID- 29039565
TI  - Hydrogen sulfide regulates bone remodeling and promotes orthodontic tooth
      movement.
AB  - Hydrogen sulfide (H2S) is a gas signaling molecule that has multiple influences
      on physiological and pathological processes in the mammalian body, including
      vasodilation, neurotransmission, inflammation, hypoxia sensing and bone
      remodeling. Our previous studies suggested that H2S might be involved in the
      periodontal tissue remodeling during the orthodontic tooth movement (OTM) via
      increasing periodontal ligament cell differentiation, tissue mineralization, bone
      formation and collagen synthesis. The aim of the present study was to investigate
      the effects of H2S on alveolar bone remodeling that is associated with tooth
      movement. Experiments were performed in an OTM mouse model. Sodium hydrosulfide
      (NaHS), which is a donor of H2S and DL-propargylglycine (PAG) and a cystathionine
      gamma-lyase (CSE) inhibitor, which could also decrease H2S expression, were
      administered intraperitoneally and respectively. A total of 60 male C57BL6/J mice
      were divided into 4 groups; Control, NaHS, PAG and combination (PAG+NaHS). The
      rate of OTM and the bone mineral density (BMD) of alveolar bone were scanned and
      measured by micro-computed tomography (micro-CT). The number of osteoclasts and
      expression of the tumor necrosis factor ligand superfamily member-11 (RANKL),
      alkaline phosphatase (ALP), osteocalcin (OCN) and osteoprotegerin (OPG) in
      alveolar bone were accessed to evaluate the osteoclastic activity and
      osteogenesis with histochemistry of tartrate-resistant acid phosphatase staining,
      immunohistochemistry and reverse transcription-quantitative polymerase chain
      reaction. In the alveolar bone, NaHS increased the OTM and decreased the BMD,
      respectively. PAG significantly decrease OTM and increased the BMD. NaHS combined
      with PAG rescued the PAG-induced changes in the OTM and the BMD. Additionally,
      the number of osteoclasts, the expression of RANKL, ALP, OCN and the ratio of
      RANKL/OPG were significantly up-regulated in the NaHS group. In contrast, PAG
      down-regulated the number of osteoclasts, the expression of RANKL, ALP, OCN and
      the ratio of RANKL/OPG. These findings suggested that H2S might facilitate the
      OTM by enhancing alveolar bone remodeling as a result of an increased
      osteoclastic activity and osteogenesis.

PMID- 29039566
TI  - MicroRNA-217 inhibits cell proliferation, invasion and migration by targeting
      Tpd52l2 in human pancreatic adenocarcinoma.
AB  - MicroRNAs (miRNAs) play important roles in the regulation of various tumor
      biological processes including proliferation and apoptosis. miR-217 has been
      implicated in many types of cancer, whereas its expression and potential
      biological function in human pancreatic adenocarcinoma (HPAC) remain unclear. We
      aimed to investigate the clinical significance of miR-217 in patients with
      pancreatic carcinoma and its role and underlying molecular mechanism in HPAC. We
      collected 15 pairs of pancreatic cancer and normal pancreas tissues to evaluate
      the expression of miR-217 and tumor protein D52-like 2 (Tpd52l2). Then, we
      transfected AsPC-1 cells with miR-217 mimics or Tpd52l2 siRNA to detect the
      effect on cell proliferation, apoptosis, invasion, migration and the cell cycle.
      In addition, miR-217 mimics and Tpd52l2 expression plasmids were co-transfected
      into AsPC-1 cells to further investigate the mechanism of miR-217 and Tpd52l2 in
      HPAC tumorigenesis. Finally, exploration of related signaling pathways was
      carried out. Herein, we found that the expression of miR-217 was significantly
      downregulated in HPAC tissues as compared with that observed in adjacent normal
      tissues. Further functional assays showed that restoration of the expression of
      miR-217 inhibited cell proliferation, invasion and migration, induced apoptosis,
      and caused cell cycle arrest of HPAC cells. Notably, Tpd52l2 was identified as a
      functional target of miR-217 in HPAC. Furthermore, an inverse correlation between
      miR-217 and Tpd52l2 expression was observed in the HPAC tissues. Downregulation
      of Tpd52l2 had an effect similar to that following overexpression of miR-217, and
      upregulation of Tpd52l2 reversed the effects of the overexpression of miR-217.
      Finally, we found that overexpression of miR-217 or knockdown of Tpd52l2
      suppressed the PIK3CA/AKT signaling pathways. In addition, this may explain the
      effect of miR-217/Tpd52l2 on HPAC development. Taken together, these results
      suggest a critical role of miR-217 in suppressing proliferation, migration and
      invasion of HPAC cells by targeting Tpd52l2. Targeting the miR-217/Tpd52l2 axis
      may be a new therapeutic application with which to treat patients with HPAC in
      the future.

PMID- 29039567
TI  - Leptin promotes IL-18 secretion by activating the NLRP3 inflammasome in RAW 264.7
      cells.
AB  - Leptin is a cytokine-like hormone secreted by adipocytes, which serves to control
      energy expenditure and metabolism. In addition, leptin may modulate the innate
      and adaptive immune responses. The innate immune cell sensor nucleotide-binding
      oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3)
      inflammasome is mainly expressed in myeloid immune cells, including macrophages.
      The NLRP3 inflammasome serves a pivotal role in the development and maintenance
      of autoimmunity and inflammation. The expression levels of caspase-1, apoptosis
      associated speck-like protein containing a CARD, interleukin (IL)-18, IL-1beta
      and leptin are significantly reduced in the white adipose tissue of nonsteroidal
      anti-inflammatory drug-activated gene-1 transgenic mice. However, the association
      between leptin and the NLRP3 inflammasome has not yet to be determined. The aim
      of the present study, was to explore the role of leptin on NLRP3 inflammasome. In
      order to do this, IL-1beta and IL-18 expression levels were investigated in RAW
      264.7 cells after incubation with leptin of increasing doses by Elisa or reverse
      transcription-quantitative polymerase chain reaction, and to assess whether IL
      1beta and IL-18 were affected after caspase-1 activity being inhibited by an
      inhibitor or by silencing NLRP3 expression. The results of the present study
      demonstrated that leptin enhanced the mRNA and protein expression levels of IL-18
      in RAW 264.7 cells via activation of the NLRP3 inflammasome. This is achieved
      partly by enhancing the production of reactive oxygen species and K+ efflux.
      Therefore, leptin may be considered a novel activator and modulator of the NLRP3
      inflammasome.

PMID- 29039568
TI  - 3,3'-Diindolylmethane attenuates cardiomyocyte hypoxia by modulating autophagy in
      H9c2 cells.
AB  - Autophagy is activated in the ischemic heart and is a process that is essential
      for survival, differentiation, development and homeostasis. 3,3'-Diindolylmethane
      (DIM) is a natural product of the acid-catalyzed condensation of indole-3
      carbinol in cruciferous vegetables. Numerous studies have suggested that DIM has
      various pharmacological effects, including antioxidant, antitumor, anti
      angiogenic and anti-apoptotic properties. However, the function of DIM on hypoxia
      induced cardiac injury remains to be elucidated. In the present study, H9c2 cells
      were pretreated with DIM (1, 5 and 10 uM) for 12 h and exposed to hypoxia for 12
      h. It was demonstrated that DIM markedly attenuated the increased transcription
      of interleukin (IL)-1beta, IL-6 and tumor necrosis factor-alpha induced by
      hypoxia. In addition, the transcription of autophagy associated genes increased
      in the DIM pretreated group, compared with the hypoxia group. DIM additionally
      attenuated the increased apoptosis, as determined by terminal deoxynucleotidyl
      transferase dUTP nick end labeling staining, and regulated the relative protein
      expression level of B cell lymphoma (Bcl) 2 associated X protein, Bcl-xL and
      cleaved caspase 3. Furthermore, the phosphorylation of the 5' AMP-activated
      protein kinase a (AMPKa) was activated and the phosphorylation of c-Jun N
      terminal kinase (JNK) was inhibited. The effect of DIM on hypoxia-induced
      apoptosis was abolished following pretreatment with JNK activator (anisomycin, 40
      ng/ml). The effect of DIM on autophagy was reversed following pretreatment with
      AMPKa inhibitor (CpC, 20 uM) following stimulation with hypoxia. The results
      demonstrated that DIM prevented hypoxia-induced inflammation and apoptosis and
      activated cardiomyocyte autophagy, which may be mediated by activation of AMPKa
      and inhibition of JNK pathways.

PMID- 29039569
TI  - Baicalin inhibits the metastasis of highly aggressive breast cancer cells by
      reversing epithelial-to-mesenchymal transition by targeting beta-catenin
      signaling.
AB  - Metastasis is the main cause of death in breast cancer patients, which is due
      partly to the lack of effective treatment. Baicalin, a flavonoid compound
      isolated from the roots of Scutellaria lateriflora Georgi (Huang Qin), has
      recently been confirmed as an effective agent for the treatment of a variety of
      cancers. Yet, the effects and underlying molecular mechanisms of baicalin in
      regards to the metastasis of breast cancer remain unclear. In the present study,
      we found that baicalin had the potential to suppress the migration and invasion
      of highly aggressive breast cancer cells in a dose-dependent manner but had no
      impact on the viability of these cancer cells. Additionally, baicalin reversed
      the epithelial-to-mesenchymal transition (EMT) process, as evaluated by EMT
      markers in breast cancer cell lines with a change from a mesenchymal feature to
      an epithelial type. At the same time, the expression of beta-catenin mRNA and
      protein was dose-dependently downregulated by baicalin in highly invasive breast
      cancer cell lines, and overexpression of beta-catenin by adenoviruses abolished
      these beneficial effects of baicalin in regards to the migration and invasion,
      and EMT of breast cancer cells. Furthermore, using a xenograft mouse model,
      baicalin markedly reduced liver and lung metastasis of breast cancer, inhibited
      expression of beta-catenin, and degraded the EMT molecules vimentin and Slug in
      the orthotopic tumor tissues. Taken together, all these results indicate that
      baicalin effectively suppresses the metastasis of breast cancer by reversing EMT,
      which may be mediated by downregulation of beta-catentin expression.

PMID- 29039570
TI  - Effect of SOX2 on odontoblast differentiation of dental pulp stem cells.
AB  - The present study aimed to investigate the effect of SOX2 on odontoblast
      differentiation of dental pulp stem cells (DPSCs), and to examine the potential
      application of DPSCs on dental restoration. SRY-box 2 (SOX2) overexpression in
      human DPSCs (DPSCs-SOX2) was established by retroviral infection. The empty
      vector-infected DPSCs were regarded as a control group (DPSCs-vector group).
      Odontoblast differentiation culture medium was used to induce the differentiation
      of DPSCs. The degree of odontoblast differentiation of DPSCs was analyzed by flow
      cytometry. A genomic expression microarray and reverse transcription-quantitative
      polymerase chain reaction were used to analyze the molecular mechanism of SOX2
      affecting odontoblast differentiation of DPSCs. After induction by odontoblast
      differentiation culture medium, the DPSC, DPSCs-vector and DPSCs-SOX2 groups all
      could carry out odontoblast differentiation. After induction for 3 weeks, all
      groups expressed dentin sialophosphoprotein (DSPP) and dentin matrix protein-1
      (DMP-1) to a certain degree. However, after induction differentiation, the
      expression efficiency of DSPP and DMP-1 in the DPSCs-SOX2 group was highest
      compared with the normal DPSC and DPSCs-vector groups, which demonstrated the
      advantages of DPSC-SOX2 in odontoblast differentiation. Mechanism analysis
      indicated that in the DPSCs-SOX2 group, the activation of the Wnt signaling
      pathway and the upregulation of Wnt genes may be important mechanisms underlying
      SOX2 promoting odontoblast differentiation of DPSCs. These results preliminarily
      indicate that SOX2 has a certain promoting effect on odontoblast differentiation
      of DPSCs.

PMID- 29039571
TI  - LARP1 is regulated by the XIST/miR-374a axis and functions as an oncogene in non
      small cell lung carcinoma.
AB  - La-related protein 1 (LARP1) is a conserved RNA-binding protein and is known to
      regulate 5'-terminal oligopyrimidine tract (TOP) mRNA translation. Dysregulated
      LARP1 has been reported to be related to the development of several cancers.
      However, the exact function and mechanism of LARP1 in non-small cell lung cancer
      (NSCLC) is largely unknown. In the present study, we found that the mRNA levels
      of LARP1 were increased in NSCLC cells compared to those in normal control cells.
      Knockdown of LARP1 inhibited cell proliferation, migration and invasion in NSCLC
      cells and tumourigenicity in H520 cells. Both in vitro and in vivo analyses
      confirmed that STAT3 signalling was inactivated by the knockdown of LARP1.
      Moreover, LARP1 was identified as a direct target of miR-374a. Overexpression of
      miR-374a attenuated the promotor effects of LARP1 by inhibiting proliferation,
      metastasis and STAT3 signalling. Clinically, LARP1 was markedly overexpressed in
      NSCLC tissues, and upregulated LARP1 was correlated with tumour progression and
      poor survival. The expression of miR-374a was negatively correlated with the
      expression of LARP1 in NSCLC tissues. Furthermore, we found that XIST functioned
      as a competing endogenous RNA to suppress miR-374a, which regulated its
      downstream target LARP1. In summary, we suggest that the dysfunction of the
      XIST/miR-374a/LARP1 axis contributes to NSCLC and may serve as a promising
      therapeutic strategy for treatment.

PMID- 29039572
TI  - Thymoquinone inhibits epithelial-mesenchymal transition in prostate cancer cells
      by negatively regulating the TGF-beta/Smad2/3 signaling pathway.
AB  - Thymoquinone, a major ingredient of black seed oil (Nigella sativa), has been
      shown to exhibit anticancer capacity in various types of cancers. However, there
      are few studies concerning the correlation between thymoquinone and epithelial-to
      mesenchymal transition (EMT) in prostate cancer. In the present study, we firstly
      found that thymoquinone showed antimetastatic capacity in prostate cancer DU145
      and PC3 cells. Additionally, thymoquinone reversed EMT by increasing E-cadherin
      expression and decreasing vimentin and Slug expression in a concentration
      dependent manner. Recent studies have shown that the transforming growth factor
      beta (TGF-beta) signaling pathway may be associated with EMT. Intriguingly, the
      expression of TGF-beta, Smad2 and Smad3 at the mRNA and protein levels was
      notably reduced upon thymoquinone treatment in prostate cancer DU145 and PC3
      cells. Subsequently, we confirmed that thymoquinone repressed metastasis and EMT
      of prostate cancer through downregulation of the TGF-beta/Smad2/3 signaling
      pathway, which may be partially reversed by TGF-beta overexpression. In summary,
      our findings demonstrated that thymoquinone suppressed the metastatic phenotype
      and reversed EMT of prostate cancer cells by negatively regulating the TGF
      beta/Smad2/3 signaling pathway. These findings suggest that thymoquinone is a
      potential therapeutic agent against prostate cancer which functions by targeting
      TGF-beta.

PMID- 29039573
TI  - Antitumor effects of baicalin on ovarian cancer cells through induction of cell
      apoptosis and inhibition of cell migration in vitro.
AB  - Baicalin, an active flavone isolated from Scutellaria baicalensis Georgi, has
      been demonstrated to induce various beneficial biochemical effects such as anti
      inflammatory, anti-viral, and antitumor effects. However, the antitumor mechanism
      of baicalin is not well understood. In the present study, baicalin was
      demonstrated to inhibit the viability and migration of a widely used ovarian
      cancer cell line, A2780, in a dose-dependent manner. MTT assays revealed that
      cell viability significantly decreased in ovarian cancer cells treated with
      baicalin compared with untreated cells, without effect on normal ovarian cells.
      Flow cytometric analysis indicated that baicalin suppressed cell proliferation by
      inducing apoptosis. The underlying mechanisms involved were indicated to be
      downregulation of the anti-apoptotic protein B-cell lymphoma 2 apoptosis
      regulator and activation of caspase-3 and -9. In addition, wound healing and
      transwell assays revealed that cell migratory potential and expression of matrix
      metallopeptidase (MMP)-2 and MMP-9 were significantly inhibited when cells were
      exposed to baicalin, compared with untreated cells. The present study therefore
      suggested that baicalin has the potential to be used in novel anti-cancer
      therapeutic formulations for treatment of ovarian cancer.

PMID- 29039574
TI  - TGF-beta1-induced cell migration in pancreatic carcinoma cells is RAC1 and NOX4
      dependent and requires RAC1 and NOX4-dependent activation of p38 MAPK.
AB  - Transforming growth factor (TGF)-beta promotes epithelial-mesenchymal transition
      and cell invasion of cancer cells in part through the small GTPase RAC1. Since
      RAC1 can signal through reactive oxygen species (ROS), we probed the role of the
      ROS-producing NADPH oxidase (NOX) and p38 mitogen-activated protein kinase (MAPK)
      in mediating TGF-beta1/RAC1-driven random cell migration (chemokinesis). Although
      the NOX isoforms NOX2, 4, 5, 6, and RAC1 were readily detectable by RT-PCR in
      pancreatic ductal adenocarcinoma (PDAC)-derived Panc1 and Colo357 cells, only
      NOX4 and RAC1 were expressed at higher levels comparable to those in peripheral
      blood monocytes. TGF-beta1 treatment resulted in upregulation of NOX4 (and NOX2)
      and rapid intracellular production of ROS. To analyze whether RAC1 functions
      through NOX and ROS to promote cell motility, we performed real-time cell
      migration assays with xCELLigence(r) technology in the presence of the ROS
      scavenger N-acetyl-L-cysteine (NAC) and various NOX inhibitors. NAC, the NOX4
      inhibitor diphenylene iodonium or small interfering RNA (siRNA) to NOX4, and the
      NOX2 inhibitor apocynin all suppressed TGF-beta1-induced chemokinesis of Panc1
      and Colo357 cells as did various inhibitors of RAC1 used as control. In addition,
      we showed that blocking NOX4 or RAC1 function abrogated phosphorylation of p38
      MAPK signaling by TGF-beta1 and that inhibition of p38 MAPK reduced TGF-beta1
      induced random cell migration, while ectopic expression of a kinase-active
      version of the p38 activating kinase MKK6 was able to partially rescue the
      decline in migration after RAC1 inhibition. Our data suggest that TGF-beta1
      induced chemokinesis in PDAC cells is mediated through a RAC1/NOX4/ROS/p38 MAPK
      cascade.

PMID- 29039575
TI  - MicroRNA-760 inhibits cell proliferation and invasion of colorectal cancer by
      targeting the SP1-mediated PTEN/AKT signalling pathway.
AB  - Colorectal cancer (CRC), one of the most commonly diagnosed types of cancer
      worldwide, is the third most prevalent and fourth most frequent cause of cancer
      related mortality. Dysregulated microRNAs (miRNAs) have potential regulatory
      roles in the development and progression of various cancer types. Therefore, the
      investigation of the miRNAs involved in CRC formation and progression may lead to
      the development of highly effective therapeutic strategies for CRC. In the
      present study, miRNA-760 (miR-760) was frequently downregulated in CRC tissues
      and cell lines. The low levels of miR-760 expression were significantly
      correlated with the tumor size, lymph node metastasis and TNM stage of CRC.
      Functional assays revealed that restoring miR-760 expression inhibited CRC cell
      proliferation and invasion in vitro. The results of bioinformatics analysis,
      luciferase reporter assay, reverse transcription-quantitative polymerase chain
      reaction and western blot analysis suggested that specificity protein 1 (SP1) is
      a direct target of miR-760 in CRC. The high expression of SP1 in CRC tissues was
      inversely correlated with the expression of miR-760. Rescue experiments
      demonstrated that enforced SP1 expression rescued the tumor-suppressing effects
      of miR-760 on CRC cell proliferation and invasion. In addition, miR-760
      overexpression is involved in the regulation of the PTEN/AKT signalling pathway.
      Collectively, the present data demonstrated that miR-760 directly targets SP1 to
      inactivate the PTEN/AKT signalling pathway, thus implicating miR-760 in the
      regulation of CRC cell proliferation and invasion. Therefore, miR-760 may be a
      novel biomarker and therapeutic target for CRC.

PMID- 29039576
TI  - Effects of ginsenoside-Rg1 on the proliferation and glial-like directed
      differentiation of embryonic rat cortical neural stem cells in vitro.
AB  - Ginsenoside-Rg1, the main active component of Panax notoginseng, exhibits a
      number of pharmacological functions, including promoting protein synthesis in the
      brain, increasing the number of synapses, improving memory and promoting recovery
      of brain function following injury. The effect of ginsenoside-Rg1 on
      proliferation and glial-like-directed differentiation in the cortical neural stem
      cells (NSCs) of embryonic rat brain was investigated. The present study used MTS
      assays to identify the optimum dose and window time of ginsenoside-Rg1
      administration to stimulate the proliferation of cortical NSCs in the rat
      embryonic tissue. The oxygen glucose deprivation (OGD) set-up was used as a cell
      injury model. Immunofluorescent staining was used for identification of NSCs and
      subsequent observation of their proliferation and glial-like directed
      differentiation. Nestin expression was the marker for the presence of NSCs among
      the cortical cells of embryonic rat brain. The optimum dose of ginsenoside-Rg1
      for proliferation of NSCs was 0.32 ug/ml. The optimum window time of 0.32 ug/ml
      ginsenoside-Rg1 administration on proliferation of NSCs was 6 h. Ginsenoside-Rg1
      at 0.32 ug/ml concentration promoted incorporation of bromo-2-deoxyuridine, and
      expression of nestin and vimentin in primary and passaged NSCs, and NSCs
      following OGD. Ginsenoside-Rg1 had a role in promoting proliferation and glial
      like-directed differentiation of cortical NSCs. The plausible explanation for
      these responses is that ginsenoside-Rg1 acts similarly to the growth factors to
      promote the proliferation and differentiation of NSCs.

PMID- 29039577
TI  - Genome-wide analysis of the three-way interplay among gene expression, estrogen
      receptor expression and chemotherapeutic sensitivity in breast cancer.
AB  - The expression of estrogen receptor alpha (ER) in breast cancers may be
      indicative of a favorable prognosis and most of these cancers respond to anti
      estrogens or aromatase inhibitors. However, ER-positive (ER+) breast cancers
      receiving anti-hormone and/or chemotherapy sometimes lose their ER expression,
      which leads to the evolution of the disease to higher aggressiveness and drug
      resistance. In the present study, an ER-modified signature (EMS) was developed
      from the expression profile of a chemoresistant MCF-7 breast cancer cell line
      that lost ER expression during long-term treatment with a chemotherapeutic agent.
      The EMS could discriminate the ER-negative (ER-) breast cancer cells from the ER+
      ones, which included seven pathways essential for the ER- cell development.
      Furthermore, the EMS indicated a more malignant subgroup of the ER- cells by
      discriminating the chemoresistant ER- cells from the chemosensitive ones. In
      addition, the classified chemoresistant ER- patients demonstrated worse
      prognosis. In conclusion, we developed a new method to discriminate subgroups of
      ER- breast cancer cells.

PMID- 29039578
TI  - The FOXM1/BUB1B signaling pathway is essential for the tumorigenicity and
      radioresistance of glioblastoma.
AB  - Accumulating evidence indicates that mitotic checkpoint serine/threonine kinase B
      (BUB1B) plays a critical role in multiple types of cancer. However, the
      biological function and molecular regulatory mechanism of BUB1B in glioblastoma
      (GBM) remain unclear. In the present study, we identified that BUB1B expression
      was enriched in GBM tumors and was functionally required for tumor proliferation
      both in vitro and in vivo. Clinically, BUB1B expression was associated with poor
      prognosis in GBM patients and BUB1B-dependent radioresistance in GBM was
      decreased by targeting BUB1B via shRNAs. Mechanistically, forkhead box protein M1
      (FOXM1) transcriptionally regulated BUB1B expression by binding to and then
      activating the BUB1B promoter. Therapeutically, we found that FOXM1 inhibitor
      attenuated tumorigenesis and radioresistance of GBM both in vitro and in vivo.
      Altogether, BUB1B promotes tumor proliferation and induces radioresistance in
      GBM, indicating that BUB1B could be a potential therapeutic target for GBM.

PMID- 29039579
TI  - Co-expression of murine double minute 2 siRNA and wild-type p53 induces G1 cell
      cycle arrest in H1299 cells.
AB  - The therapeutic options available for the treatment of advanced non-small cell
      lung cancer have increased over the past decade. Small molecule gene therapy has
      emerged as an effective therapy for the treatment of lung cancer in vitro and in
      vivo although it has not been tested in a clinical setting. In particular,
      therapies that target the negative feedback loop between p53 and murine double
      minute 2 (MDM2) provide a favorable outcome by maintaining activation of the
      tumor suppressor gene p53. The present study used transfection to simultaneously
      knockdown MDM2 expression using small interfering (si)RNA, and overexpress wild
      type p53 in H1299 cells. The effects of transfection on cell proliferation and
      cell cycle progression were determined using an MTT assay and flow cytometry, and
      the effects on mRNA and protein expression were determined by western blotting
      and reverse transcription polymerase chain reaction. The results indicated that
      simultaneously knocking down MDM2 and overexpressing p53 was able to inhibit
      proliferation and induce G1 cell cycle arrest in H1299 cells, compared with
      either alone. These findings indicated that the si-MDM2-p53 co-expression plasmid
      may induce cell cycle arrest, and may be considered a novel therapeutic option
      for the treatment of lung cancer.

PMID- 29039580
TI  - Combination of oncolytic adenovirus and luteolin exerts synergistic antitumor
      effects in colorectal cancer cells and a mouse model.
AB  - In recent years, oncolytic viruses have attracted increasing interest due to
      their potent antitumor effects. Luteolin, a natural product, has additionally
      been observed to exhibit various pharmacological antitumor activities.
      Previously, a novel dual-targeting oncolytic adenovirus, complement decay
      accelerating factor (CD55)-tumor necrosis factor ligand superfamily member 10
      (TRAIL), was constructed, which exhibited significant growth inhibitory effects
      in various types of tumor cell. The present study investigated whether the
      combination of luteolin and CD55-TRAIL was able to exert a synergistic antitumor
      effect in colorectal carcinoma (CRC) cells. The cytotoxicity and tumor cell
      apoptosis mediated by combination treatment in CRC cells were detected via an MTT
      assay, Hoechst staining and western blotting, respectively. Tumor growth in vivo
      was examined in a CRC mouse xenograft model following various treatments. The
      results demonstrated that the addition of luteolin enhanced oncolytic adenovirus
      mediated enhanced green fluorescent protein, early region 1A and TRAIL
      expression. The combination of CD55-TRAIL with luteolin synergistically inhibited
      tumor growth and promoted CRC cellular apoptosis in vitro and in vivo.
      Additionally, the combination of CD55-TRAIL with luteolin significantly decreased
      cytotoxicity in lung/bronchial normal epithelial cells, compared with single
      treatment. Therefore, the combination of CD55-TRAIL with luteolin may be a novel
      efficient therapeutic strategy for CRC in the future.

PMID- 29039581
TI  - Shikonin induces apoptosis and G0/G1 phase arrest of gallbladder cancer cells via
      the JNK signaling pathway.
AB  - Shikonin, a natural product isolated from the roots of Lithospermum
      erythrorhizon, is considered to have antitumor effects. Gallbladder cancer (GBC)
      is a prevalent biliary tract malignancy with few curative therapeutic stragegies
      and poor prognosis. In the present study, we detected the effects of shikonin on
      GBC cells as well as the underlying molecular mechanisms. The results
      demonstrated that GBC cell proliferation was inhibited by shikonin as determined
      by MTT and colony formation assays. Flow cytometry results demonstrated that
      shikonin treatment enhanced apoptosis and promoted G0/G1 phase arrest in the GBC
      cells. Western blot assay showed that shikonin induced mitochondrial-dependent
      apoptosis via the JNK signaling pathway. Moreover, shikonin suppressed tumor
      growth in mice bearing GBC-derived xenografts in a dose-dependent manner without
      side-effects. These results revealed that shikonin exhibits anticancer effects on
      GBC cells by inducing apoptosis and regulating the cell cycle. Taken together,
      shikonin may be a novel and safe chemotherapeutic agent for the treatment of GBC.

PMID- 29039582
TI  - Curcumol inhibits the proliferation of gastric adenocarcinoma MGC-803 cells via
      downregulation of IDH1.
AB  - Curcumol, a polyphenol compound derived from the rhizome of Curcuma, has been
      established as an antitumor compound against multiple types of cancer, including
      gastric (GC), lung, liver and breast cancer. However, the molecular mechanisms
      undelying its anticancer activity in GC are still unclear. In this study, the
      antitumor efficacy of curcumol was ascertained in human gastric adenocarcinoma
      MGC-803 cells. An MTT assay was used to assess the viability of the MGC-803 cells
      treated by curcumol. The results of the Annexin V/propidium iodide (PI) staining
      followed by fluorescence activated cell sorting (FACS) analysis demonstrated that
      the cell cycle was arrested in the G2/M phase by curcumol. Annexin V-FITC/PI
      double staining followed by FACS analysis revealed that curcumol induced
      apoptosis of MGC-803 cells. FACS analysis after the cells were loaded with a DFCH
      DA probe revealed that the level of reactive oxygen species (ROS) increased after
      the cells were treated with curcumol. In adittion, FACS analysis after the cells
      were loaded with JC-1 revealed that the level of mitochondrial membrane potential
      (MMP) decreased after the cells were treated with curcumol. Furthermore, the
      downregulation of isocitrate dehydrogenase 1 (IDH1) was observed in the MGC-803
      cells after being treated with curcumol as determined by western blotting and RT
      qPCR. In conclusion, we elucidated the antitumor effect of curcumol on MGC-803
      cells and the involved mechanisms related to the induction of apoptosis, the
      increase of ROS, the decrease of MMP and the downregulation of IDH1.

PMID- 29039583
TI  - Serum metabolomic profile in genetically modified cows carrying human alpha
      lactalbumin gene.
AB  - The present study aimed to investigate the serum metabolomic profiles in
      genetically modified cows carrying and expressing human lactalbumin alpha (LALBA)
      and non-LALBA cows, and identify altered metabolic characteristics following the
      genetic modification. Serum biochemistry indexes were measured according to
      protocols recommended by International Federation of Clinical Chemistry. The
      metabolomic profiles were determined using the serum samples collected from LALBA
      (n=6) and non-LALBA cows (n=6). Welch's two-sample t-test was used to identify
      the metabolites that significantly differed between the LALBA and non-LALBA
      groups (fold-change ? 1 and P<0.05), followed by random forest and pathway
      analysis. The serum biochemistry indexes of LALBA and non-LALBA cows were within
      the normal ranges of healthy cows. A total of 273 metabolites were detected,
      among which 79 metabolites, including 46 increased and 33 decreased metabolites,
      differed significantly between the LALBA and non-LALBA groups. Random forest
      analysis identified 30 potential key metabolites, including 14 elevated and 16
      reduced metabolites. These metabolites were primarily involved in pathways
      concerning the metabolism of leucine, isoleucine, valine, tryptophan and lipids,
      such as myristate and eicosapentaenoate. However, the serum in LALBA cow had
      unique metabolomic signature compared with non-LALBA cows. The accumulation of
      polyunsaturated fatty acids and amino acids, and the reduced levels of long chain
      saturated fatty acids in serum may benefit LALBA cows. However, further
      investigations are required to validate these benefits and the corresponding
      mechanisms.

PMID- 29039584
TI  - BAF53a is a potential prognostic biomarker and promotes invasion and epithelial
      mesenchymal transition of glioma cells.
AB  - Increasing evidence indicates that BAF53a is crucial for embryonic development
      and maintenance of stemness, and may be associated with epithelial-mesenchymal
      transition (EMT), which suggests its involvement in cancer progression. However,
      the role of BAF53a in glioma remains unknown. In the present study, BAF53a was
      found to be highly expressed in glioma tissues and was associated with poor
      overall survival (OS) and progression-free survival (PFS) in glioma patients. A
      multivariate Cox regression analysis revealed that BAF53a might be an independent
      prognostic factor for OS and PFS in glioma patients. Further functional analysis
      indicated that BAF53a overexpression could promote proliferation and increase the
      motility and invasion of U87 glioma cells, whereas BAF53a knockdown had the
      opposite effect. In addition, BAF53a expression was associated with the levels of
      E-cadherin and vimentin expression in glioma tissues. This was further confirmed
      in U87 cells expressing different levels of BAF53a; BAF53a overexpression was
      concomitant with decreased E-cadherin and increased vimentin expression, whereas
      BAF53a knockdown showed the opposite pattern of expression. Taken together, these
      results suggest that BAF53a may be a novel prognostic factor for glioma patients,
      and that BAF53 may facilitate glioma progression by promoting proliferation,
      invasion, and associate with EMT. Therefore, BAF53a could be a potential
      promising biomarker and a target for the treatment of glioma.

PMID- 29039585
TI  - Identification of genome variations in patients with lung adenocarcinoma using
      whole genome re-sequencing.
AB  - Lung adenocarcinoma is one of the types of non-small cell lung carcinoma, which
      tends to be treated with surgical therapy rather than radiation therapy. It
      occurs in smokers and non-smokers, and is the most common form of lung cancer
      among non-smokers and women. Gene rearrangements, including ALK, ROS1 and RET,
      and gene mutations, including epidermal growth factor receptor (EGFR), HER2,
      Kristen rat sarcoma viral oncogene homolog, BRAF, phosphoinositide-3-kinase,
      catalytic, alpha polypeptide and MET, have been identified in lung
      adenocarcinoma, which enable targeted therapy in lung adenocarcinoma, for example
      erlotinib, gefitinib and afatinib, which are EGFR inhibitors. The aim of the
      present study was to further investigate genome variations in lung
      adenocarcinoma. Single nucleotide polymorphisms (SNPs), insertions and deletions
      (InDels), structural variations (SVs) and copy number variations (CNVs) were
      identified in the whole genome from four patients with adenocarcinoma using a
      whole genome re-sequencing method performed on the Illumina HiSeq Xten platform.
      In total, ~415 GB of clean reads were obtained, the average sequencing depth was
      31.10-fold, and 99.29% of the reference genome was covered by the clean reads. An
      average of 3,364,270 SNPs was identified, 98.76% of which were matched to the SNP
      database (dbSNP), and an average of 453,547 InDels were identified, 28.28% of
      which were in the dbSNP. The present study also identified a total of 13,050 SVs
      and 886 CNVs. The majority of the SVs were deletions (74.25%) and the major CNVs
      were in intergenic regions and coding sequence regions. In conclusion, the
      results of the present study generated an output of the genome alterations in
      lung adenocarcinoma, and provided a foundation for further investigation of the
      pathogenesis of lung adenocarcinoma.

PMID- 29039586
TI  - A single nucleotide polymorphism located in microRNA-499a causes loss of function
      resulting in increased expression of osbpl1a and reduced serum HDL level.
AB  - Atherosclerosis is the main pathological process that induces CVD (cardiovascular
      diseases), and the objective of our study was explore whether miR-499a rs3746444
      polymorphism was associated with the HDL level, one of the risk factors of
      atherosclerosis. Online public miRNA database was utilized to predict the miR
      499a target, and luciferase assay was conducted to confirm that miR-499a targeted
      osbpl1a, then western blot analysis and real-time PCR were performed to verify
      miRNA-mRNA regulatory relationship between miR-499a and osbpl1a. Based on results
      of bioinformatics algorithms, osbpl1a was predicted as a candidate target gene of
      miR-499a, luciferase reporter was generated, and it was found that the luciferase
      activity of cells was substantial downregulated following co-transfection with
      wild osbpl1a 3'UTR and miR-499a compared to that in scramble control, while the
      inhibitory effect of miR-499a was abolished after transfection of mutant osbpl1a
      3'UTR. Then, miRNA-mRNA regulatory relationship between miR-499a and osbpl1a was
      detected, a concentration-dependent effect of miR-499a on the miR-499a expression
      was observed, and both osbpl1a mRNA and protein levels of cells transfected with
      miR-449a (30 and 60 nM) or osbpl1a siRNA were markedly reduced, while notably
      improved subsequent to transfect with anti-miR-449a (30 and 60 nM) in comparison
      with NC groups, moreover, the inhibitory effect among 30 or 60 nM miR-499a,
      osbpl1a siRNA was similar, the improved effect of 30 or 60 nM anti-miR-499a
      showed no significant change. The influence of rs3746444 A allele on expression
      level of miR-499a represented a recessive pattern in high-grade group with a
      higher level of miR-499a in AA group, and HDL level in AA group was significantly
      reduced related to those in AG and GG groups. This study validated that rs3746444
      polymorphism influenced the expression of miR-499a, its target gene, osbpl1a, and
      thereby associated with the HDL level, which makes it a potential factor involved
      in the mechanism of atherosclerosis.

PMID- 29039587
TI  - Protective effects of rosmarinic acid against hydrogen peroxide-induced cellular
      senescence and the inflammatory response in normal human dermal fibroblasts.
AB  - Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that induces numerous
      cellular events, including cellular senescence and inflammatory responses.
      Therefore, the aim of this study was to investigate the protective effect of
      Rosmarinic acid (RA) in H2O2-induced oxidative stress in normal human dermal
      fibroblasts (NHDFs). Cytotoxicity assays were performed using a water-soluble
      tetrazolium salt, and senescence-associated beta-galactosidase activity was
      determined to investigate the proportion of senescent cells. Antioxidant
      capacities were evaluated via H2O2-scavenging activity, reverse transcription
      quantitative polymerase chain reaction, NRF2 luciferase reporter gene activity
      and intracellular ROS scavenging assays. Cytokine-coded gene expression analysis
      and nuclear factor-kappaB luciferase activity were determined to verify the anti
      inflammatory effect of RA. As a result, the present study demonstrated that
      rosmarinic acid inhibited H2O2-induced oxidative stress and inflammatory
      responses in normal human dermal fibroblasts. Initially, the doses of RA that
      exerted minimal cytotoxic effects in NHDFs were determined using a cytotoxicity
      assay. Subsequently, pretreatment with the appropriate doses of RA significantly
      reversed the H2O2-induced decrease in NHDF cell viability and decreased cellular
      senescence of NHDFs. In addition, RA inhibited H2O2-induced ROS production in
      NHDFs, as determined by a ROS scavenging assay. The protective effects of RA were
      mediated by the inhibition of nuclear factor erythroid-derived 2-like 2, a
      transcription factor that functions as a key regulator of redox sensitivity.
      Furthermore, RA suppressed H2O2-induced inflammation in NHDFs and significantly
      rescued H2O2-induced downregulation of sirtuin 1. RA also inhibited nuclear
      factor (NF)-kappaB transcriptional activity and the expression of NF-kappaB
      target genes, including tumor necrosis factor-alpha and interleukin-6, in H2O2
      exposed NHDFs. Taken together, these data indicate that RA inhibits H2O2-induced
      cellular damage in NHDFs.

PMID- 29039588
TI  - A panel of markers for identification of malignant and non-malignant cells in
      culture from effusions.
AB  - The aim of the present study was to identify cell types in primary culture from
      malignant and non-malignant effusions. Effusion samples were subjected to
      cytology and culture. Immunocytochemistry was performed in cytological slides to
      evaluate malignancy (positivity for malignancy markers) and in culture slides for
      identification of cell types in growth. A total of 143 effusion samples (pleural
      n=76; peritoneal n=37; pericardial n=4; and peritoneal lavage n=26) were
      analyzed. Cell growth was observed in 34.9% of all samples and
      immunocytochemistry for identification of cell types in culture slides was
      conclusive in 90% of them. In non-malignant samples (n=28), growth of mesothelial
      cells, macrophages and of both cell types was identified in 82.14, 10.71 and
      7.14%, respectively. In malignant samples (n=17, all carcinomas), growth of
      malignant epithelial cells and of both malignant epithelial and mesothelial cells
      was identified in 41.17 and 23.52%, respectively. In the remaining 35.29% of
      malignant samples, the only cells in growth were mesothelial and/or macrophages
      instead of malignant epithelial cells. In conclusion, in culture of malignant
      effusions, mesothelial cells may be simultaneously identified with malignant
      epithelial cells. Besides, mesothelial cells and macrophages may be the only
      cells identified in malignant effusion culture. Therefore, a broad panel of cell
      markers should be used for unmistakable identification of cells in studies of
      effusion primary culture. The ideal malignant effusion sample to obtain culture
      of neoplastic cells should be that without the presence of mesothelial cells and
      macrophages.

PMID- 29039589
TI  - Partial monosomy 8p and trisomy 16q in two children with developmental delay
      detected by array comparative genomic hybridization.
AB  - Two cases of liveborn unrelated children with developmental delay and overlapping
      unbalanced translocations der(8)t(8;16)(p23.2;q23.3) and der
      (8)t(8;16)(p23.1;q23.1), leading to partial monosomy 8p and partial trisomy 16q,
      are reported in the present study. The first patient was a 10-year-old boy with
      mild developmental delay and minor congenital anomalies (borderline microcephaly,
      clinodactyly, hypertelorism, epicanthus, mild systolic murmur and kidney reflux).
      The second patient was a 3 year-old girl with developmental delay, gross motor
      milestone delay and dysmorphic features. Array-comparative genomic hybridization
      analysis revealed that partial chromosome 8p monosomy extended from 8p23.2 to
      8pter (4.8 Mb) in Patient 1 and from 8p23.1 to 8pter (9.5 Mb) in Patient 2, and
      partial chromosome 16 trisomy extended from 16q23.3 to 16qter (5.6 Mb) in Patient
      1 and from 16q23.1 to 16qter (11.7 Mb) in Patient 2. The mechanism of appearance
      of the rearrangement in association with the genes involved and the architecture
      of the region is discussed.

PMID- 29039590
TI  - MicroRNA-218 promotes prostaglandin E2 to inhibit osteogenic differentiation in
      synovial mesenchymal stem cells by targeting 15-hydroxyprostaglandin
      dehydrogenase [NAD(+)].
AB  - The chondrogenic differentiation of synovial mesenchymal stem cells (SMSCs) is
      regulated by essential transcription factors and signaling cascades. However, the
      precise mechanisms involved in this process remain unclear. MicroRNAs
      (miRs/miRNAs) are undersized non-coding RNAs responsible for the post
      transcriptional regulation of gene expression, by binding to the 3'-untranslated
      regions (3'-UTRs) of their target mRNAs. miRNAs may constitute a promising tool
      to regulate SMSC differentiation and to advance the controlled differentiation of
      SMSCs in therapeutic applications. The aim of the present study was to examine
      the role of miR-218 in SMSC differentiation towards chondrocytes. The present
      study comparatively analyzed the expression profile of known miRNAs and specific
      target genes in SMSCs between early and late differentiation stages. Western
      blotting and reverse transcription-quantitative polymerase chain reaction
      analysis of gene expression demonstrated the upregulation of 15
      hydroxyprostaglandin dehydrogenase [NAD(+)] (15-HPGD), prostaglandin E2 (PGE2)
      and rate limiting enzymes responsible for the synthesis of PGE2 precursors
      throughout chondrogenesis. Through correlation analysis, it was observed that
      there was a significant association between miR-128, 15-HPGD gene expression, 15
      HPGD protein expression and microsomal prostaglandin E synthase 1. Further
      experiments demonstrated that miR-218 decreased PGE2 concentration by binding to
      the 3'-UTR of 15-HPGD. Using an immunofluorescence reporting system, it was
      observed that miR-218 regulated the expression of 15-HPGD during the
      differentiation of SMSCs into cartilage, and subsequently inhibited osteogenesis
      during chondrogenesis by acting on the 3'UTR of 15-HPGD. Therefore, miR-218 may
      be an important regulator targeting osteogenic factors and modulating cartilage
      formation and differentiation. The results of the present study provided a novel
      insight beneficial to cellular manipulation methods during cartilage
      regeneration, and in cartilage tissue engineering research.

PMID- 29039591
TI  - Dabrafenib in patients with recurrent, BRAF V600E mutated malignant glioma and
      leptomeningeal disease.
AB  - BRAF V600E mutations occur frequently in malignant melanoma, but are rare in most
      malignant glioma subtypes. Besides, more benign brain tumors such as
      ganglioglioma, dysembryoblastic neuroepithelial tumours and supratentorial
      pilocytic astrocytomas, only pleomorphic xanthoastrocytomas (50-78%) and
      epitheloid glioblastoma (50%) regularly exhibit BRAF mutations. In the present
      study, we report on three patients with recurrent malignant gliomas harbouring a
      BRAF V600E mutation. All patients presented with markedly disseminated
      leptomeningeal disease at recurrence and had progressed after radiotherapy and
      alkylating chemotherapy. Therefore, estimated life expectancy at recurrence was a
      few weeks. All three patients received dabrafenib as a single agent and all
      showed a complete or nearly complete response. Treatment is ongoing and patients
      are stable for 27 months, 7 months and 3 months, respectively. One patient showed
      a dramatic radiologic and clinical response after one week of treatment. We were
      able to generate an ex vivo tumor cell culture from CSF in one patient. Treatment
      of this cell culture with dabrafenib resulted in reduced cell density and
      inhibition of ERK phosphorylation in vitro. To date, this is the first series on
      adult patients with BRAF-mutated malignant glioma and leptomeningeal
      dissemination treated with dabrafenib monotherapy. All patients showed a dramatic
      response with one patient showing an ongoing response for more than two years.

PMID- 29039592
TI  - Inhibition of cell migration and invasion by miR-29a-3p in a colorectal cancer
      cell line through suppression of CDC42BPA mRNA expression.
AB  - The objective of this study was to determine the effect of miR-29a-3p inhibitor
      on the migration and invasion of colorectal cancer cell lines (CRC) and the
      underlying molecular mechanisms. miR-29a-3p was detected using reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR) in the CRC cell
      lines HCT11, CaCo2, HT29, SW480 and SW620. An invasive subpopulation designated
      SW480-7 was derived from the parental cell line, detected by Transwell and
      Transwell Matrigel assays. Cytoskeleton Regulators RT2 profiler PCR array and
      western blot analysis were utilized to identify the alterations in expression of
      downstream mRNAs. siRNA against CDC42BPA was transfected into SW480-7 and effects
      on cell migration and invasion were investigated. Data obtained showed that miR
      29a-3p was detected in these five CRC cell lines. miR-29a-3p inhibitor had no
      effect on viability but stimulated cell migration and invasion of SW480-7 cells.
      In contrast, miR-29a-3p mimic suppressed cell migration and invasion. TargetScan
      miRBD and DIANA were employed to identify the potential direct target genes of
      miR-29a-3p in the Cytoskeleton Regulators RT2-Profiler PCR array. Cytoskeleton
      Regulators RT2-Profiler PCR array data showed that 3 out of the 5 predicted
      targets genes, CDC42BPA (2.33-fold), BAIAP2 (1.79-fold) and TIAM1 (1.77-fold), in
      the array were upregulated by miR-29a-3p. A significant increase in expression
      IQGAP2, PHLDB2, SSH1 mRNAs and downregulation of PAK1 mRNA was also detected with
      miR-29a-3p inhibition. Increase in CDC42BPA, SSH1 and IQGAP2 mRNA expression
      correlated with increased protein level in miR-29a-3p transfected SW-480-7 cells.
      Silencing of CDC42BPA (an enhancer of cell motility) partially abolished miR-29a
      3p inhibitor-induced stimulation of cell migration and invasion. miR-29a-3p
      expression in stage II and III CRC is relatively lower than that of stage I CRC.
      However, the data need to be interpreted with caution due to the small sample
      size. In conclusion, inhibition of miR-29a-3p stimulates SW480-7 cell migration
      and invasion and downstream expression IQGAP2, PHLDB2, SSH1 mRNAs are upregulated
      whilst PAK1 mRNA is downregulated. Silencing of CDC42BPA expression partially
      reduces miR29a-3p inhibitor-induced migration and invasion of SW480-7 cells.

PMID- 29039594
TI  - Overexpression of Stathmin 1 correlates with poor prognosis and promotes cell
      migration and proliferation in oesophageal squamous cell carcinoma.
AB  - Stathmin 1 (STMN1) is a microtubule-regulated protein that plays an important
      role in tumour cell proliferation and migration. Overexpression of STMN1 is
      associated with clinicopathological characteristics in many human cancers. The
      aim of the present study was to investigate STMN1 expression, its correlation
      with clinicopathological characteristics, and its exact biological function in
      oesophageal squamous cell carcinoma (ESCC). STMN1 levels were measured in the
      ESCC tissue specimens of 276 patients by immunohistochemistry (IHC) to assess the
      prognostic efficacy of STMN1. IHC showed that patients with overexpression of
      STMN1 had a poorer prognosis compared with those with low expression, both in
      regards to 5-year overall survival (OS; 21.2 vs. 53.7%, P<0.001) and disease-free
      survival (DFS; 20.6 vs. 50.9%, P<0.001). STMN1 overexpression was associated with
      lower cell differentiation in tumour grade (correlation coefficient: 0.127,
      P=0.037). In multivariate analysis, STMN1 expression was found to be an
      independent prognostic factor for both OS (P<0.001; 95% CI, 1.555-2.970) and DFS
      (P=0.001; 95% CI, 1.978-2.444). Compared with the control, STMN1 downregulation
      significantly decreased cell migration, invasion and proliferation, whereas these
      were increased by STMN1 upregulation. STMN1 expression was significantly
      associated with prognosis and tumour differentiation in ESCC, indicating that
      STMN1 expression is an independent prognostic factor for ESCC and could be a
      potential biomarker. Regulating the expression of STMN1 could influence tumour
      cell motility, invasion and proliferation.

PMID- 29039593
TI  - Hyperthermia with different temperatures inhibits proliferation and promotes
      apoptosis through the EGFR/STAT3 pathway in C6 rat glioma cells.
AB  - Malignant gliomas are a group of aggressive neoplasms among human cancers. The
      curative effects of current treatments are finite for improving the prognosis of
      patients. Hyperthermia (HT) is an effective treatment for cancers; however, the
      effects of HT with different temperatures in treatment of MG and relevant
      mechanisms remain unclear. MTT assay and Annexin V-fluorescein
      isothiocyanate/propidium iodide staining were used for investigating the
      proliferation and apoptosis of C6 cells, respectively. Western blotting was
      applied to detect the expression of proteins. Ultrasonography was employed to
      evaluate the tumor formation rate, growth rate, angiogenesis rate and degree of
      hardness of tumors in vivo. The authors certified that HT with 42-46C x 1 h, 1 t
      could inhibit proliferation, promote apoptosis, reduce tumor formation rate,
      growth rate, angiogenesis rate, degree of hardness of tumors, ischemic tolerance
      and anoxic tolerance, and have synergy with temozolomide in C6 cells. Long-term
      HT (43C x 1 h, 1 t/5 d, 90 d) did not cut down the sensitivity of C6 cells to HT,
      and sustainably inhibited the proliferation of C6 cells. Furthermore, the authors
      proved HT produced these effects primarily through inhibition of the
      EGFR/STAT3/HIF-1A/VEGF-A pathway.

PMID- 29039595
TI  - Caveolin-1 regulates oxidative stress-induced senescence in nucleus pulposus
      cells primarily via the p53/p21 signaling pathway in vitro.
AB  - Previous studies have indicated that cellular senescence is a critical underlying
      mechanism of intervertebral disc degeneration. However, the precise mechanism by
      which cellular senescence accelerates disc degeneration has not been fully
      elucidated. Caveolin-1 has recently emerged as an important regulator of cellular
      senescence. Therefore, the aim of the present study was to investigate whether
      caveolin-1 is involved in nucleus pulposus (NP) cellular senescence during
      oxidative stress. PCR was used to detect caveolin-1 mRNA expression and protein
      expression was detected by western blotting. Caveolin-1 expression at the mRNA
      and protein levels was markedly increased following treatment with tert-butyl
      hydroperoxide, and an increase in premature senescence was observed, as
      determined by senescence-associated beta-galactosidase staining and the decline
      of cellular proliferative ability. In addition, caveolin-1 gene expression was
      successfully knocked down by lentivirus-mediated RNA interference, which exerted
      a protective effect against the cellular senescence induced by oxidative stress.
      Notably, p53 and p21 protein expression, though not p16 protein expression,
      decreased with caveolin-1 silencing. The results suggested that caveolin-1 may be
      involved in NP cellular senescence during oxidative stress in vitro, mainly via
      the p53/p21 signaling pathway. Thus, caveolin-1 may represent a novel therapeutic
      target for the prevention of intervertebral disc degeneration.

PMID- 29039596
TI  - The role of the miR-99b-5p/mTOR signaling pathway in neuroregeneration in mice
      following spinal cord injury.
AB  - The present study aimed to investigate the role of microRNA (miR)-99b-5p in
      spinal cord injury (SCI). Reverse transcription-quantitative polymerase chain
      reaction demonstrated that, compared with control mice, the expression levels of
      miR-99b-5p were upregulated in the mouse spinal cord following SCI. Mechanistic
      target of rapamycin (mTOR) was predicted to be the possible target of miR-99b-5p
      according to TargetScan and microrna databases. Dual-luciferase reporter assay
      verified that miR-99b-5p was able to target mTOR. Furthermore, the results of an
      apoptosis analysis demonstrated that there were few apoptotic neurons in the
      control group, whereas SCI induced a significant increase in the number of
      apoptotic cells. Conversely, apoptosis was inhibited following transfection with
      a miR-99b-5p inhibitor. The effects of miR-99b-5p on neurite growth were also
      evaluated. The results of an immunofluorescence analysis indicated that neurite
      growth was normal in the control group, whereas SCI induced a reduction in
      neurite growth, which was rescued following transfection with a miR-99b-5p
      inhibitor. The protein expression levels of mTOR were detected in the three
      groups by western blotting. The results demonstrated that, compared with the
      control group, the protein expression levels of mTOR were significantly reduced
      in SCI neurons, whereas transfection with a miR-99b-5p inhibitor suppressed the
      SCI-induced reduction of mTOR. In conclusion, treatment with a miR-99b-5p
      inhibitor may attenuate SCI-induced harmful alterations in spinal cord neurons
      via the regulation of mTOR expression.

PMID- 29039597
TI  - Whole-genome scale identification of methylation markers specific for cerebral
      palsy in monozygotic discordant twins.
AB  - Cerebral palsy (CP) is a severe type of brain disease affecting movement and
      posture. Although CP has strong genetic and environmental components,
      considerable differences in the methylome between monozygotic (MZ) twins
      discordant for CP implicates epigenetic contributors as well. In order to
      determine the differences in methylation in patients with CP without interference
      of the interindividual genomic variation, four pairs of MZ twins discordant for
      CP were profiled for DNA methylation changes using reduced representation
      bisulfite sequencing on the genomic-scale. Similar DNA methylation patterns were
      observed in all samples. However, MZ twins demonstrated higher correlations and
      closer evolutionary associations compared with the other samples, indicating a
      stable methylome of MZ twins. A total of 190 differentially methylated genes
      (DMGs) were identified using Student's t-test, of which 37 genes were
      hypermethylated in the CP group while the remainders were hypomethylated compared
      with control group. The identified DMGs were enriched in several cerebral
      abnormalities, including cerebral cortical atrophy and cerebral atrophy,
      suggesting that the occurrence of CP may be associated with the methylation
      alterations. The neighboring genes of DMGs in the protein-protein interaction
      network were enriched in numerous important functions in essential processes. The
      results of the present study identified important genes that may epigenetically
      contribute to the occurrence and development of CP in MZ twins, suggesting that
      the different prevalence of CP in identical twins may be associated with DNA
      methylation alterations.

PMID- 29039598
TI  - Expression of key enzymes in the mevalonate pathway are altered in monocrotaline
      induced pulmonary arterial hypertension in rats.
AB  - Pulmonary arterial hypertension (PAH) is a serious pulmonary vascular disease.
      The changes in the structure, function and metabolism of endothelial cells are
      some of the important features of PAH. Previous studies have demonstrated that
      the mevalonate pathway is important in cardiovascular remodeling. However,
      whether the mevalonate pathway is involved in the development of PAH remains to
      be elucidated. The present study aimed to investigate the expression pattern of
      mevalonate pathway-related enzymes in monocrotaline (MCT)-induced PAH. F344 rats
      were randomly divided into two groups (n=6/group): Control group rats were
      injected with a single dose of saline, and MCT group rats were injected with a
      single dose of MCT (60 mg/kg). After 4 weeks, the right ventricular systolic
      pressure (RVSP) was measured, and lung and pulmonary artery tissue samples were
      collected. It was demonstrated that the RVSP increased and pulmonary vascular
      remodeling was detected in the PAH group. The expression levels of the enzymes
      farnesyldiphosphate synthase farnesyltransferase alpha and
      geranylgeranyltransferase type I increased in the PAH group, which suggested that
      the mevalonate pathway may be involved in the pathological development of PAH.

PMID- 29039599
TI  - Suppressive role of miR-592 in breast cancer by repressing TGF-beta2.
AB  - The function of miR-592 has been investigated in many types of cancer, however
      its roles in breast cancer remain unclear. We therefore investigated the
      biological function and underlying mechanism of miR-592 in breast cancer. In the
      present study, a marked downregulation of miR-592 was observed in breast cancer
      tissues and cell lines compared to the matched adjacent non-tumor tissues and
      normal breast cell line. Statistical analysis revealed that decreased miR-592 was
      negatively associated with advanced clinical stage, distant metastasis and lymph
      node metastases. Function analysis demonstrated that overexpression of miR-592
      significantly inhibited cell proliferation, clone formation, migration and
      invasion in breast cancer cells in vitro, as well as suppressed tumor growth in
      vivo. Furthermore, transforming growth factor beta-2 (TGFbeta-2), a known
      oncogene, was identified as a direct target of miR-592, and its mRNA expression
      level was inversely correlated with the expression level of miR-592 in human
      breast cancer specimens. Restoration of TGFbeta-2 expression rescued the
      inhibitory effect in breast cancer cells caused by miR-592. Collectively, these
      data suggest that miR-592 may exert it suppressive role in breast cancer, at
      least in part, by targeting TGFbeta-2, and that miR-592 may be a novel target for
      breast cancer treatment.

PMID- 29039600
TI  - Synergism between alpha-mangostin and TRAIL induces apoptosis in squamous cell
      carcinoma of the oral cavity through the mitochondrial pathway.
AB  - Mangosteen (Garcinia mangostana) is a tree found in South-East Asia and the
      pericarp of its fruit has been used in folk medicine for the treatment of many
      human illnesses. Mangosteen fruit rinds contain a high concentration of xanthone,
      which is a type of polyphenol. One type of xanthone, alpha-mangostin, has been
      reported to exert chemopreventive effects against chemically-induced colon cancer
      through the decrease of c-Myc expression, suppressing tumor growth in a mouse
      model of mammary cancer. A recent study demonstrated the inhibitive effect of
      alpha-mangostin on the growth of prostate cancer. However, it remains unclear
      whether alpha-mangostin induces cell death in oral cancer. The present study
      examined the impact of alpha-mangostin on human oral squamous cell carcinoma
      (HOSCC). Firstly we analyzed the expression of c-Myc in five HOSCC cell lines.
      The highest expression level of c-Myc mRNA was observed in SAS cells and the
      lowest in HSC-4 cells. Therefore, SAS cells were treated with alpha-mangostin,
      which was found to exert a weak cytocidal effect. Since alpha-mangostin has been
      reported to exert synergistic effects on cancers when combined with anticancer
      drugs, we attempted to evaluate such synergistic effects of alpha-mangostin when
      used with a cytokine, tumor necrosis factor (TNF)-related apoptosis-inducing
      ligand (TRAIL). We found that the combination of alpha-mangostin with TRAIL
      induced apoptosis of SAS cells through the mitochondrial pathway via activation
      of caspase-9 and -3/7, following release of cytochrome c. This apoptosis was
      induced by S/G2/M-phase arrest. Immunopositivity for c-Myc was observed in the
      cytoplasm of tumor cells in 16 (40%) of the 40 cases of HOSCC. These data
      revealed that the combination of alpha-mangostin and TRAIL may have a
      considerable potential for the treatment of oral cancer.

PMID- 29039601
TI  - Vasohibin2 promotes adriamycin resistance of breast cancer cells through
      regulating ABCG2 via AKT signaling pathway.
AB  - As a well-known angiogenic factor in different histology and pathological
      conditions, the pro-progressive role of vasohibin2 (VASH2) has been reported in
      various types of tumors. However, its role in drug resistance of breast cancer
      has not been reported so far. The present study demonstrated that MCF-7 cells
      with increased expression of VASH2 demonstrate stronger adriamycin (ADM)
      resistance compared with MDA-MB-231 cells with decreased expression of VASH2.
      Overexpression of VASH2 in MDA-MB-231 cells increased ADM resistance and
      silencing VASH2 in MCF-7 cells inhibited ADM resistance. Furthermore, in newly
      established ADM resistant cell lines, VASH2 was significantly upregulated. These
      results revealed the promotive role of VASH2 in the ADM resistance of breast
      cancer cells. In addition, overexpression of VASH2 in MDA-MB-231 cells
      significantly upregulated ATP-binding cassette sub-family G member 2 (ABCG2),
      however silencing VASH2 in MCF-7 cells inhibited ABCG2 significantly. Silencing
      ABCG2 abrogated increase of ADM resistance induced by VASH2 overexpression in MDA
      MB-231 cells. This proved that VASH2 induced ADM resistance through promoting
      expression of ABCG2, at least in part. Further study regarding the underlying
      molecular mechanism demonstrated that VASH2 promoted ABCG2 via the protein kinase
      B (AKT) signaling pathway. Overall, VASH2 may promote drug resistance of breast
      cancer cells through regulating ABCG2 via the AKT signaling pathway. This
      suggests a novel therapeutic target to inhibit drug resistance in breast cancer,
      for a more efficient therapeutic outcome.

PMID- 29039602
TI  - lncRNA-MIAT regulates cell biological behaviors in gastric cancer through a
      mechanism involving the miR-29a-3p/HDAC4 axis.
AB  - Gastric cancer (GC) is one of the most common malignant diseases worldwide.
      Although significant progress has been made in the early detection and treatment
      of GC over the past decades, the prognosis is still not satisfactory and the
      underlying mechanisms of carcinogenesis remain unknown. Long non-coding RNA MIAT
      has been established as a key player in the regulation of various biological and
      pathological processes including chronic lymphocytic leukemias, acute myocardial
      infarction and neuroendocrine prostate cancer. However, the function of MIAT in
      GC remains largely unknown. The expressions of lncRNA MIAT, miR-29a-3p and HDAC4
      mRNA were analysed using quantitative real-time PCR (qRT-PCR). RNA interference
      approach was used to investigate the cellular functions of MIAT and miR-29a-3p.
      Cell Counting Kit-8 (CCK-8) assay and flow cytometry assay were performed to
      detect cell proliferation and apoptosis. Cell migration and invasion abilities
      were evaluated by Transwell assays. In the present study, we first confirmed the
      high expression level of MIAT in GC tissues and cell lines. In addition,
      knockdown of MIAT suppressed the proliferation, migration and invasion of GC
      cells in vitro. Furthermore, our results demonstrated that MIAT competitively
      binds to miR-29a-3p and consequently upregulates the expression of HDAC4, which
      is a downstream target of miR-29a-3p. In conclusion, the present study
      highlighted the involvement of the MIAT/miR-29a-3p/HDAC4 axis in the development
      of GC, which provided potential diagnostic and therapeutic targets for GC.

PMID- 29039603
TI  - Blockade of alpha7 nicotinic acetylcholine receptors inhibit nicotine-induced
      tumor growth and vimentin expression in non-small cell lung cancer through
      MEK/ERK signaling way.
AB  - Nicotine can stimulate the progression of non-small cell lung cancer (NSCLC)
      through nicotinic acetylcholine receptors (nAChRs). The persistent proliferation
      of cancer cells is one of the key effects of nicotinic signaling. The present
      study aimed to clarify the mechanism of nicotine-induced proliferation in NSCLCs
      at the receptor subtype level. We have previously reported that there are various
      subtypes of nicotinic receptors expressed in NSCLC cell lines. In the present
      study, we demonstrated that blocking alpha7nAChRs agonized by nicotine could
      suppress the proliferation of H1299 cells in vitro and decrease H1299 tumor
      xenograft growth in nude mice. During this process, the expression of vimentin
      was also markedly attenuated, concomitant with the decreased expression of
      alpha7nAChR. These results were ascertained by knocking down the alpha7nAChR gene
      to abolish receptor functioning. Furthermore, under the stimulation of nicotine,
      the MEK/ERK signaling pathway was found to be inhibited when cells were treated
      with an antagonist of alpha7nAChR or an inhibitor of MEK. Collectively the
      results indicate that the changes in proliferation and vimentin expression of
      H1299 cells in response to alpha7nAChR stimulation are mediated by the MEK/ERK
      pathway. These findings demonstrate that alpha7nAChR plays an important role in
      H1299 cell proliferation, tumor growth and expression of vimentin. Therefore,
      blocking alpha7nAChRs in NSCLC may be a potential adjuvant therapy for the
      targeted treatment of NSCLC.

PMID- 29039604
TI  - Elevated pentose phosphate pathway is involved in the recovery of hypoxia-induced
      erythrocytosis.
AB  - As a typical model of hypoxia-induced excessive erythrocytosis, high altitude
      polycythemia (HAPC) results in microcirculation disturbance, aggravates tissue
      hypoxia and results in a severe clinical outcome, without any effective
      intervention methods except for returning to an oxygen-rich environment. The
      present study aimed to explore potential therapeutic targets which may
      participate in the recovery of HAPC by studying the mechanisms of reducing the
      hemoglobin (HB) concentration during re-oxygenation. A total of 14 and 13
      subjects were recruited over a 5,300 m distance and 5,170 m area. The patients
      were classified into HAPC or control groups based on their HB value. Plasma
      samples were collected on the day when they finished their stay in plateau for a
      year, and on the 180th day following their reaching in plain. Metabolic profiling
      was conducted by UPLC-QTOF/MS. MetaboAnalyst platform was performed to explore
      the most perturbed metabolic pathways. A panel of differential metabolites were
      obtained in the recovery phase of HAPC and control groups. The present study
      identified the uniquely upregulated pentose phosphate pathway in HAPC subjects,
      along with a significantly decreased HB level. The findings were verified via a
      direct comparison between HAPC and control subjects at a high altitude. An
      increased pentose phosphate pathway was identified in control groups compared
      with HAPC subjects. An elevated pentose phosphate pathway may therefore
      participate in the recovery of HAPC, whereas a downregulated pentose phosphate
      pathway may contribute to hypoxia-induced erythrocytosis. The results of the
      present study provide potential therapeutic strategies and novel insights into
      the pathogenesis of hypoxia-induced polycythemia.

PMID- 29039605
TI  - Knockdown of HIP1 expression promotes ligand-induced endocytosis of EGFR in HeLa
      cells.
AB  - Huntington-interacting protein 1 (HIP1) is associated with various tumor types;
      however, its precise functions in tumor cells are unclear. In this study, the
      effects of HIP1 on the degradation of EGFR, which have important roles in
      carcinogenesis after EGF stimulation, were examined. After screening 17 cell
      lines, the coexpression of HIP1 and EGFR was detected in HeLa cells. Accordingly,
      the expression of HIP1 was knocked down in HeLa cells using various HIP1 siRNA
      sequences. The endocytosis of EGFR and localization of clathrin in HeLa cells
      were examined after stimulation by EGF at various concentrations (i.e., 1.5 and
      100 ng/ml). After HIP1 expression was blocked by siRNAs, EGFR endocytosis was
      accelerated and this effect was dependent on the EGF concentration. This
      endocytosis was colocalized with clathrin expression. These findings indicate
      that the inhibition of HIP1 can accelerate the endocytosis and degradation of
      EGFR. Furthermore, they suggest that HIP1 is a potential therapeutic target for
      various cancer types, particularly those with high EGFR expression, but further
      research is needed to examine this hypothesis.

PMID- 29039606
TI  - Expression, regulation and mechanism of action of the miR-17-92 cluster in tumor
      cells (Review).
AB  - MicroRNAs (miRNAs), a class of short, single-stranded non-coding RNAs, regulate
      and control gene expression in eukaryotes by degrading mRNA at the post
      transcriptional level. Regulation by miRNAs involves a plethora of biological
      processes, such as cell differentiation, proliferation, metastasis, metabolism,
      apoptosis, tumorigenesis and others. miRNAs also represent a powerful tool in
      disease diagnosis and prognosis. The miR-17-92 cluster, one of the most
      extensively investigated microRNA clusters, comprises six mature miRNA members,
      including miR-17, miR-18a, miR-19a, miR-19b, miR-20a and miR-92a. Originally
      identified as being involved in tumorigenesis, it is currently evident that the
      expression of the miR-17-92 cluster is upregulated in a wide range of tumor cells
      and cancer types; thus, this cluster has been identified as a potential oncogene.
      Considering the growing interest in the field of miR-17-92 research, we herein
      review recent advances in the expression and regulation of this cluster in
      various cancer cells, discuss the proposed mechanism of action for tumorigenesis
      and tumor development, and propose clinical and therapeutic applications for miR
      17-92 cluster members, such as potential cancer biomarkers.

PMID- 29039608
TI  - Livin promotes the progression and metastasis of breast cancer through the
      regulation of epithelial-mesenchymal transition via the p38/GSK3beta pathway.
AB  - Epithelial-mesenchymal transition (EMT) plays a pivotal role in the invasion and
      metastasis of breast cancer. Livin is a recently identified member of the
      inhibitors of the apoptosis protein family, which has been revealed to facilitate
      the progression of several types of cancer. However, the role of Livin in EMT and
      metastasis of breast cancer and its underlying mechanisms are not fully
      elucidated. In the present study, the levels of Livin mRNA and protein expression
      were found to be elevated in breast cancer tissues and cell lines. In addition,
      Livin expression was positively correlated with TNM stage and lymph node
      metastasis in total and triple-negative breast cancer (TNBC) cases. Livin
      overexpression enhanced the migratory and invasive abilities of the MCF-7 cells,
      accompanied by increases in vimentin, N-cadherin, Snail, MMP-2 and MMP-7 and a
      decrease in E-cadherin. Conversely, the downregulation of Livin had the opposite
      effect in MDA-MB-231 cells. Furthermore, the upregulation of Livin expression
      markedly stimulated the activation of the p38/GSK3beta pathway, while the
      downregulation of Livin expression clearly suppressed the activation of the
      p38/GSK3beta pathway. In conclusion, our results revealed that Livin induced EMT
      through the activation of the p38/GSK3beta pathway, which in turn promoted the
      progression and metastasis of breast cancer, especially for TNBC.

PMID- 29039607
TI  - Downregulation of miR-874-3p promotes chemotherapeutic resistance in colorectal
      cancer via inactivation of the Hippo signaling pathway.
AB  - Overcoming resistance to chemotherapy is an arduous challenge in the treatment of
      colorectal cancer (CRC), particularly since the underlying molecular mechanisms
      remain obscure. In the present study, we reported that miR-874-3p was markedly
      downregulated in CRC tissues compared with that in adjacent normal colorectal
      epithelial tissues. Upregulation of miR-874-3p attenuated the chemoresistance of
      CRC cells to 5-fluorouracil (5-FU) in vitro and in vivo. Conversely, inhibition
      of miR-874-3p yielded an opposite effect. Furthermore, our results demonstrated
      that miR-874-3p directly inhibited the expression of transcriptional co
      activators YAP and TAZ of the Hippo signaling pathway, resulting in the
      inactivation of the TEAD transcription. Thus, our findings clarify a novel
      mechanism by which miR-874-3p restores chemotherapeutic sensitivity of CRC to 5
      FU, indicating that offering miR-874-3p mimics in combination with 5-FU may serve
      as a new therapeutic strategy to circumvent the chemoresistance in CRC.

PMID- 29039609
TI  - Quercetrin from Toona sinensis leaves induces cell cycle arrest and apoptosis via
      enhancement of oxidative stress in human colorectal cancer SW620 cells.
AB  - Finding effective strategies against colorectal cancer (CRC) is still an emergent
      health problem. In the present study, we investigated the anticancer activity of
      quercetrin from Toona sinensis leaves (QTL) and explored the underlying mechanism
      in human CRC cell line SW620. The cells were treated with various concentrations
      of QTL and the cytotoxic effects of QTL were determined using the MTT assay.
      Apoptosis and cell cycle status were detected by flow cytometry. Reactive oxygen
      species (ROS) levels and mitochondrial membrane potential (?Psim) were assessed
      using DCF-DA and JC-1 fluorescence spectrophotometry, respectively. Western blot
      analysis was used to quantify the expression of apoptosis-related proteins. RT
      PCR was applied to determine the mRNA levels of glutathione peroxidase (GPx) and
      catalase (CAT). QTL exhibited growth inhibitory effects and caused cell cycle
      arrest in the G2/M phase, which was accompanied by increased expression of p53
      and p21 proteins. QTL promoted apoptosis which was consistent with the
      upregulated expression of Bax, cytochrome c, caspase-9, Apaf-1 and caspase-3. In
      addition, QTL induced the loss of mitochondrial membrane potential and triggered
      ROS generation, as revealed by the downregulated mRNA expression and enzymatic
      activity of GPx and CAT. Furthermore, both N-acetyl cysteine (NAC) and GSH
      attenuated the QTL-induced growth inhibition observed in SW620 cells along with
      the increase of ROS levels. These findings revealed that QTL inhibited the growth
      of CRC cells and facilitated apoptosis by enhancing oxidative stress. QTL may
      therefore have potential for use in CRC chemotherapy.

PMID- 29039611
TI  - Altered expression of different GalNAc-transferases is associated with disease
      progression and poor prognosis in women with high-grade serous ovarian cancer.
AB  - Protein glycosylation perturbations are implicated in a variety of diseases,
      including cancer. Aberrant glycosylation in cancer is frequently attributed to
      altered expression of polypeptide GalNAc transferases (GalNAc-Ts) - enzymes
      initiating mucin-type O-glycosylation. A previous study from our group
      demonstrated that one member of this family (GALNT3) is overexpressed in
      epithelial ovarian cancer (EOC), and GALNT3 expression correlated with shorter
      progression-free survival (PFS) in EOC patients with advanced disease. As
      considerable degree of redundancy between members of the GalNAc-Ts gene family
      has been frequently observed, we decided to investigate whether other members of
      this family are essential in EOC progression. In silico analysis based on
      publically available data was indicative for altered expression of five GalNAc-Ts
      (GALNT2, T4, T6, T9 and T14) in ovarian high-grade serous carcinoma (HGSC)
      samples compared to non-tumoral (control) ovarian tissue. We analyzed protein
      expression of these GalNAc-Ts in EOC cells and tumors by western blotting,
      followed by immunohistochemical (IHC) evaluation of their expression in EOC tumor
      and control samples using tissue microarrays (TMAs). Western blot analyses were
      indicative for low expression of GALNT2 and strong expression of GALNT6, T9 and
      T14 in both EOC cells and tumors. These observations were confirmed by IHC.
      GALNT2 displayed significantly lower expression, while GALNT6, GALNT9 and GALNT14
      showed significantly higher expression in HGSC tumors compared to control tissue.
      Importantly, GALNT6 and GALNT14 expression correlated with poor prognosis of
      serous EOC patients. Moreover, our results suggest for overlapping functions of
      some GalNAc-Ts, more specifically GALNT3 and GALNT6, in directing EOC
      progression. Our results are indicative for a possible implication of different
      members of the GalNAc-T gene family in modulating EOC progression, and the
      potential use of GALNT6 and GALNT14 as novel prognostic EOC biomarkers. These
      data warrant future studies on the role of members of the GalNAc-Ts gene family
      in ovarian tumorigenesis.

PMID- 29039610
TI  - Establishment of a human primary pancreatic cancer mouse model to examine and
      investigate gemcitabine resistance.
AB  - Pancreatic cancer is one of the most fatal types of cancer and is associated with
      a dismal prognosis. Gemcitabine-based chemotherapy is clinically used for the
      treatment of advanced pancreatic cancer. However, many forms of pancreatic cancer
      have acquired resistance to gemcitabine. In order to prevent patients from
      suffering from the side effects of chemotherapy and to have the chance to receive
      more effective intervention, assessment of whether the patient pancreatic cancer
      cells are resistant to gemcitabine before clinical practice is crucial. Recently,
      patient-derived xenograft (PDX) models have been regarded as a practical approach
      for preclinical drug resistance test. In the present study, we harvested tumor
      specimens from 28 pancreatic cancer patients to establish PDX models. The tumor
      formation rate of the xenografts was 100%, several of which could be re-implanted
      in nude mice for more than 10 passages. Primary cells were further obtained from
      the PDX xenografts to determine their morphological features and evaluate their
      proliferation rate, migration capacity and angiopoietic ability. In addition, the
      sensitivities of the primary cells and PDX xenografts to gemcitabine were
      correlated with each other. When compared to the gemcitabine-sensitive cells, the
      gemcitabine-resistant cells had a higher level of MCF2L expression, suggesting
      that MCF2L plays an important role in gemcitabine resistance.

PMID- 29039612
TI  - Long non-coding RNA, steroid receptor RNA activator (SRA), induces tumor
      proliferation and invasion through the NOTCH pathway in cervical cancer cell
      lines.
AB  - Contemporary research has focused on the function of long non-coding RNAs
      (lncRNAs) in carcinogenesis. However, the involvement of the lncRNA, steroid
      receptor RNA activator (SRA), in cervical carcinogenesis remains to be
      elucidated. In the present study, we investigated the bio-functional consequences
      of lncRNA SRA knockdown in vitro. To verify the role of lncRNA SRA in cell
      proliferation, migration, and invasion, lncRNA RNA interference was utilized to
      knock down lncRNA SRA expression in cervical cancer cell lines, resulting in our
      discovery that lncRNA SRA knockdown inhibited cell proliferation, cell migration
      and tumor invasion in the cervical cancer cell lines. Additionally, in vitro
      experiments using the lncRNA SRA-knockdown cervical cancer cell lines revealed
      that lncRNA SRA is a strong inducer and modulator of the expression of genes
      related to epithelial-mesenchymal transition and the NOTCH signaling pathway. In
      conclusion, our findings demonstrated that lncRNA SRA is highly correlated with
      cancer progression and cervical cancer cell proliferation and migration.
      Furthermore, these results indicate that lncRNA SRA may be a potential
      therapeutic target and prognostic marker for cervical malignancy.

PMID- 29039614
TI  - Substitutions of rtL228 and/or L229 are involved in the regulation of replication
      and HBsAg secretion in hepatitis B virus, and do not affect susceptibility to
      nucleos(t)ide analogs.
AB  - Nucleos(t)ide analogs (NAs) are widely used in the treatment of hepatitis B virus
      (HBV) and human immunodeficiency virus (HIV). The mutation L210W of HIV-1 reverse
      transcriptase (RT) is one of the six principal mutations which confer in vivo
      resistance to zidovudine. Due to the similar 3D-structure and high conservation
      between HIV-RT and HBV-RT, the present study aimed to clarify whether
      corresponding mutations in HBV may decrease its susceptibility to relevant NAs.
      Mutations including rtL228C/W, rtL229W and rtL228W/L229W were introduced into a
      HBV replication competent plasmid by fusion polymerase chain reaction.
      Replication capacity, HBs/e antigen (Ag) levels and susceptibility to NAs were
      subsequently analyzed in vitro. Single or combination mutations of rtL228 and
      rtL229 impaired HBV replication. Decreased HBsAg secretion in the supernatant and
      production in the cell lysate wasobserved with single rtL229W or in combination
      with rtL228W, while there was no significant difference between wild-type and
      mutant HBV with regard to the level of HBeAg in the supernatant and
      susceptibility to commonly-used NAs. Substitution mutations of rtL228 and/or L229
      in HBV did not alter the susceptibility of the virus to NAs, although replication
      and HBsAg secretion were affected.

PMID- 29039613
TI  - Staphylococcus aureus colonisation in patients from a primary regional hospital.
AB  - Staphylococcus aureus (SA or S. aureus) is a common pathogen that leads to local
      and systemic infections in communitarian and hospitalised patients.
      Staphylococcus colonizing nasal or pharyngeal sites can become virulent and cause
      severe infections. In this study, we collected 322 pharyngeal exudates and 142
      nasal exudates from hospitalised and outpatients for screening purposes. The
      carriage rates in the pharynx were 27.06% for S. aureus, 11.55% for methicillin
      resistant S. aureus (MRSA) and 5.61% for methicillin-oxacillin resistant S.
      aureus (MORSA). The carriage rates in the nose were 35.38% for S. aureus, 18.46%
      for MRSA and 13.85% for MORSA. The median multiple antibiotic resistance (MAR)
      index of SA was 33.33%. The MAR of MRSA was significantly higher than that of
      methicillin-susceptible strains (MSSA) (45.45% vs. 18.75%, P<0.0001) and the MAR
      of MORSA was 57.14%. Hierarchical clustering analysis revealed differences in the
      resistance of methicillin-sensitive, MRSA and MORSA strains. On the whole, our
      study demonstrates the pattern of distribution of nasal and pharyngeal
      colonisation with SA, MRSA and MORSA in adults vs. children, inpatients vs.
      outpatients, ICU patients vs. non-ICU patients, and females vs. males, which can
      be used for adjusting the screening and decontamination protocols in a hospital.
      SA is a pervasive pathogen with constantly changing trends in resistance and
      epidemiology and thus requires constant monitoring in healthcare facilities.

PMID- 29039615
TI  - Effects of deferoxamine on the osteogenic differentiation of human periodontal
      ligament cells.
AB  - Hypoxia regulates a number of cell biological processes, including cell survival,
      development and differentiation. Deferoxamine (DFO), an oral chelator for blood
      transfusion patients, has been demonstrated to induce hypoxia and is frequently
      used as a hypoxia-mimicking agent. The purpose of the present study was to
      investigate the influence of DFO on the proliferation, migration and osteogenic
      differentiation of human periodontal ligament cells (hPDLCs). The effects of DFO
      on hPDLC viability and migration were measured using an MTT and wound healing
      assay. To characterize the hypoxia microenvironment, the expression of hypoxia
      inducible factor-1alpha (HIF-1alpha) in hPDLCs treated with DFO was quantified
      using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR).
      Subsequently, the osteogenic differentiation potential of DFO was determined by
      RT-qPCR of the mRNA of osteogenic markers (runt-related transcription factor 2
      [Runx-2], osteopontin [OPN] and collagen type I [Col-1]). The alkaline
      phosphatase activity and mineral deposition were analyzed using alizarin red S
      staining. The MTT and wound healing assays demonstrated that low-concentrations
      of DFO had little impact on hPDLC viability and migration 48 h into the
      treatment. DFO upregulated the expression of hPDLC genes specific for osteogenic
      differentiation: HIF-1alpha, Runx-2, OPN and Col-1. Furthermore, formation of
      mineralized nodules was enhanced by DFO. The present study suggests that DFO
      provided favorable culture conditions to promote the osteogenic differentiation
      and mineralization of hPDLCs. The mechanism underlying these alterations remains
      to be elucidated.

PMID- 29039616
TI  - Cisplatin-induced autophagy protects breast cancer cells from apoptosis by
      regulating yes-associated protein.
AB  - Breast cancer is a common cause of cancer-related deaths in women. Treatment with
      cisplatin exhibits some therapeutic efficacy. However, treatment optimization is
      required, and the mechanisms underlying the cisplatin's proapoptotic effects
      remain unclear. In the present study, we demonstrated that cisplatin induced
      apoptosis and autophagy in breast cancer cells. Autophagy induced by cisplatin
      played a protective role in breast cancer cells, which impaired its proapoptotic
      effect. Mechanistically, for the first time, we found that cisplatin treatment
      activated the MAPK signaling pathway and promoted autophagy via the ERK signaling
      pathway. Notably, we found that nuclear translocation of yes-associated protein
      (YAP) was regulated by cisplatin-induced autophagy, and we identified YAP as a
      survival input that promoted survival in cisplatin-treated breast cancer cells.
      These findings revealed that administration of cisplatin along with an autophagy
      inhibitor is a promising therapeutic strategy for treating breast cancer.

PMID- 29039617
TI  - The electrical properties and glass transition of some dental materials after
      temperature exposure.
AB  - The physicochemical properties of dental materials will remain stable only when
      these materials in question are resistant to the changes in the oral cavity. The
      oral environment is subject to large temperature variations. The aim of the study
      was the assessment of electrical properties and glass transition of some dental
      materials after temperature exposure. Composite materials, compomers, materials
      for temporary prosthetic replacement and resin-based pit and fissure sealants
      were used in the study. The method used was electric conductivity of materials
      under changing temperature. The order of materials presenting the best
      characteristics for insulators was as follows: materials for temporary prosthetic
      replacement, resin-based pit and fissure sealants, composites, and compomers.
      Thanks to comparisons made between graphs during I and II heating run, the method
      could be used to observe changes in the heated material and determine whether the
      changes observed are reversible or permanent. The graphs also provided
      temperature values which contain information on glass transition during heating.
      In the oral cavity the effect of the constant temperature stimulus influences
      maturity of dental materials and improves their properties. But high temperatures
      over glass transition temperature can cause irreversible deformation and changes
      of the materials properties, even in a short time.

PMID- 29039618
TI  - Sterilizing photocurable materials by irradiation: preserving UV-curing
      properties of photopolymers following E-beam, gamma, or X-ray exposure.
AB  - We have developed novel photopolymer gels to function as separators in blood
      collection tubes. By incorporating antioxidants such as alpha-tocopherol and
      nitroxides (TEMPO and TEMPOL), the new formulation can be sterilized with
      electron beam or gamma rays at a dose level of 17 kGy, without inducing premature
      curing of the photopolymers. For the blood separator gels that contain alpha
      tocopherol, our results show that alpha-tocopherol plays a decisive role in
      impeding C-centered free radical propagation reactions through an H-transfer
      mechanism. This mechanism involves the transfer of an H-atom from the hydroxyl
      group (OH) of alpha-tocopherol to the propagating C-centered radical leading to
      the termination of the polymerization. The sterilization radiation-induced
      premature curing of the photopolymer was also prevented in the blood separator
      gel containing nitroxides. For the gels containing TEMPO or TEMPOL, inhibition of
      the premature curing was achieved through an addition reaction or an H-transfer
      reaction, respectively. Our results also show that while alpha-tocopherol is not
      a contributing factor in the subsequent (time-of-use) UV curing of the gels,
      nitroxides enhance the UV curing process through nitroxide-mediated living free
      radical polymerization reactions leading to a decrease in UV curing time. The
      photopolymer separator gels are shown to function advantageously in clinical
      laboratory testing, especially for cell-free DNA measurements in blood.

PMID- 29039619
TI  - Evaluation of corrosion behavior in artificial saliva of 2507 and 2205 duplex
      stainless steel for orthodontic wires before and after heat treatment.
AB  - The present study investigates comparison between corrosion behavior of 2507 and
      2205 DSS in artificial saliva for orthodontic wires. The heat treatment is
      necessary for 2507 and 2205 duplex stainless steel to remove or dissolve
      intermetallic phases, removed segregation and to relieve any residual thermal
      stress in DSS which may be formed during production processes. The corrosion
      behavior of a 2507 and 2205 DSS in artificial saliva was studied by SEM, HV test
      and potentiodynamic measurements. The results indicate that the corrosion
      resistance mainly depends on presence of secondary phases (sigma phase) and
      ferrite /austenite ratio, it's revealed that the corrosion resistance of 2507 DSS
      higher than 2205 DSS in artificial saliva at 37  degrees C.

PMID- 29039620
TI  - Preoperative Genetic Testing and Personalized Medicine: Changing the Care
      Paradigm.

PMID- 29039621
TI  - Supporting Emergency Medical Care Teams with an Integrated Status Display
      Providing Real-Time Access to Medical Best Practices, Workflow Tracking, and
      Patient Data.
AB  - The work of a hospital's medical staff is safety critical and often occurs under
      severe time constraints. To provide timely and effective cognitive support to
      medical teams working in such contexts, guidelines in the form of best practice
      workflows for healthcare have been developed by medical organizations. However,
      the high cognitive load imposed in such stressful and rapidly changing
      environments poses significant challenges to the medical staff or team in
      adhering to these workflows. In collaboration with physicians and nurses from
      Carle Foundation Hospital, we first studied and modeled medical team's individual
      responsibilities and interactions in cardiac arrest resuscitation and decomposed
      their overall task into a set of distinct cognitive tasks that must be
      specifically supported to achieve successful human-centered system design. We
      then developed a medical Best Practice Guidance (BPG) system for reducing medical
      teams' cognitive load, thus fostering real-time adherence to best practices. We
      evaluated the resulting system with physicians and nurses using a professional
      patient simulator used for medical training and certification. The evaluation
      results point to a reduction of cognitive load and enhanced adherence to medical
      best practices.

PMID- 29039623
TI  - The challenge of Takotsubo syndrome: heterogeneity of clinical features.
AB  - Takotsubo syndrome (TTS) was first described in 1991 as a rare, spontaneous and
      completely reversible left ventricular regional systolic dysfunction. Today the
      incidence of TTS is estimated at 2% in patients with an initial diagnosis of
      acute coronary syndrome (ACS). Notably, the incidence can be as high as 5.9 to
      7.5% in female patients. TTS occurs predominantly in postmenopausal women, but
      both sexes may be affected, at any age. Acute chest pain or dyspnoea is a
      characteristic symptom of TTS, but initial presentation can also include more
      severe disease manifestation such as acute heart failure with pulmonary oedema or
      haemodynamic instability, especially in an in-hospital setting. It is now known
      that TTS is triggered by not only emotional, but also physical stressors, or a
      combination of both. Although apical ballooning is the most frequent and typical
      finding on imaging, different types of TTS have been described, including the
      midventricular, basal and focal forms. The acute phase of TTS may be complicated
      by cardiogenic shock, left ventricular outflow tract obstruction, severe mitral
      valve regurgitation, embolisation of ventricular thrombi and life-threatening
      ventricular arrhythmias. Furthermore, although originally thought to be a
      completely reversible condition, the long-term prognosis of TTS is not entirely
      positive, with a major adverse cardiac and cerebrovascular event (MACCE) rate of
      9.9% reported in the InterTAK Registry, the largest series of patients with TTS.
      The exact aetiology of TTS remains unknown, there are no current treatment
      guidelines and differential diagnosis from the more frequent ACS entities remains
      particularly challenging. Overall, TTS remains a poorly understood and under
      diagnosed disease, sometimes disguised in clinically atypical presentations. This
      review presents different TTS cases to illustrate that TTS is a heterogeneous
      disease.

PMID- 29039622
TI  - Quality of vitamin K antagonist oral anticoagulation in 322 patients with atrial
      fibrillation - real-life data from a survey in Eastern Switzerland.
AB  - AIM OF THE STUDY: To better appreciate the role of the non-vitamin K oral
      anticoagulants (NOACs) for patients with non-valvular atrial fibrillation in
      Switzerland we aimed to assess the quality of vitamin K antagonist (VKA)
      anticoagulation in daily practice. METHODS: In a cross-sectional study,
      clinically stable patients on VKA treatment for non-valvular atrial fibrillation
      for at least 6 months, documentation of international normalised ratio (INR)
      values for at least 3 months and with at least two INR values were included. The
      percentage of INR values within the therapeutic range of 2.0 to 3.0 and the time
      in therapeutic range (TTR; Rosendaal method) and predictors for these measures of
      VKA anticoagulation quality were assessed. RESULTS: We studied 332 patients (62%
      male, mean age 74 +/- 9 years) with median (interquartile range) CHA2DS2Vasc and
      HAS-BLED scores of 4 (3-5) and 3 (2-4) points. The median number of INR values
      per patient was 8 (5-14), and the average interval between INR measurements was
      20 (13-27) days. The percentage of INR values between 2.0 and 3.0 was 67% (50
      83%). The median TTR was 69% (51-89%), and TTR >=65% was found in 202 (61%)
      patients. Independent predictors of >=80% INR values between 2.0 and 3.0 included
      a longer interval between INR measurements and the non-use of spironolactone. The
      non-use of amiodarone and spironolactone and a longer interval between INR
      measurements were the only independent predictors of a TTR >=65%. CONCLUSIONS:
      The quality of VKA anticoagulation in Switzerland is highly variable.
      Importantly, only 60% of patients achieve a TTR >=65%, which is currently
      considered to be the minimal acceptable TTR required for VKA therapy. There are
      few clinical predictors of a good VKA anticoagulation quality. These data may
      represent a novel basis for decision making regarding the choice of
      anticoagulation for atrial fibrillation in Switzerland.

PMID- 29039624
TI  - Factors associated with cessation of smoking among Swiss adults between 1991 and
      2011: results from the SAPALDIA cohort.
AB  - INTRODUCTION: Smoking is still the most preventable cause of disease and
      premature death in Switzerland, as elsewhere. We aimed to assess the main
      determinants of smoking cessation in the population-based cohort of SAPALDIA
      (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults).
      METHODS: The SAPALDIA study was initiated in 1991 with 9651 participants aged 18
      to 60 years from eight areas (S1). Follow-up assessments were conducted in 2002
      (S2; 8047 participants) and 2010/11 (S3; 6088 participants). At each survey,
      detailed information on health and potential health-related factors was collected
      and lung function measured. Using logistic regression, we assessed predictors of
      smoking cessation between S1 and S2 and between S2 and S3. RESULTS: In both
      periods, highest educational level (summary odds ratio [OR] 1.49, 95% confidence
      interval [CI] 1.08-2.06; ref. lowest level), FEV1/FVC <0.5 (OR 6.19, 95% CI 2.44
      15.7, ref. FEV1/FVC >=0.7), higher age in men (OR 1.02, 95% CI 1.01-1.03, per
      year) and overweight (OR 1.38, 95% CI 1.16-1.64) were significant predictors of
      smoking cessation. Nicotine dependence (OR 0.97, 95% CI 0.96-0.98, per cigarette
      smoked a day) and female sex between age 45 and 60 (e.g., OR 0.74, 95% CI 0.61
      0.91, at age 50) were negatively associated with smoking cessation. Moreover,
      smokers at S2 reporting a diagnosis of depression were less likely to quit
      smoking by S3 (OR 0.53, 95% CI 0.30-0.93). CONCLUSIONS: Prospective tobacco
      control policies in Switzerland should be addressed to women, younger persons and
      persons of lower education.

PMID- 29039625
TI  - Genetic determinants of the epigenome in development and cancer.
AB  - Although we have detailed maps of epigenetic marks on DNA and chromatin for many
      cell types and disease states, the origin and significance of these patterns is
      incompletely understood. Deregulation of the epigenome is a frequent
      accompaniment to cancer, and it is therefore important that we learn how it
      contributes to tumour formation. Here it is proposed that the roles of DNA
      sequence signals as determinants of the epigenome have been underappreciated.
      Taking as a paradigm the part played by the dinucleotide CpG in regulating gene
      expression via its effects on the epigenome, it is suggested that factors
      recognising other short, frequent sequence motifs also recruit chromatin
      modifying enzymes in response to DNA sequence. A screen for factors of this kind
      promises to aid our understanding of the mechanisms by which gene activity is
      globally regulated.

PMID- 29039626
TI  - An appreciation of Sir Adrian Peter Bird: winner of the Charles Rodolphe
      Brupbacher Prize for Cancer Research 2017.

PMID- 29039627
TI  - Beliefs, endorsement and application of homeopathy disclosed: a survey among
      ambulatory care physicians.
AB  - BACKGROUND: Explanation models for the effectiveness of homeopathy are not
      supported by natural sciences and the aggregated evidence from clinical trials is
      unconvincing. From this standpoint, placebo effects seem the most obvious
      explanation for the therapeutic effects experienced in homeopathy. Still, many
      physicians continue to prescribe homeopathic treatments. OBJECTIVES: Whether
      physicians who prescribe homeopathic treatments aim to achieve placebo effects or
      actually believe in specific effects is poorly understood. However, this
      distinction has important educational and ethical implications. Therefore, we
      aimed to describe the use of homeopathy among physicians working in outpatient
      care, factors associated with prescribing homeopathy, and the therapeutic
      intentions and attitudes involved. METHODS: All physicians working in outpatient
      care in the Swiss Canton of Zurich in the year 2015 (n = 4072) were approached.
      Outcomes of the study were: association of prescribing homeopathy with medical
      specialties (odds ratios [OR] and 95% confidence intervals [95% CI] from
      multivariable logistic regression); intentions behind prescriptions (to induce
      specific or nonspecific/placebo effects); level of agreement with specific
      attitudes; and views towards homeopathy including explanatory models, rating of
      homeopathy's evidence base, the endorsement of indications, and reimbursement of
      homeopathic treatment by statutory health insurance providers. RESULTS: The
      participation rate was 38%, mean age 54 years, 61% male, and 40% specialised in
      general internal medicine. Homeopathy was prescribed at least once a year by 23%
      of the respondents. Medical specialisations associated with prescribing
      homeopathy were: no medical specialisation (OR 3.9; 95% CI 1.7-9.0),
      specialisation in paediatrics (OR 3.8 95% CI 1.8-8.0) and gynaecology/obstetrics
      (OR 3.1 95% CI 1.5-6.7). Among prescribers, only 50% clearly intended to induce
      specific homeopathic effects, only 27% strongly adhered to homeopathic
      prescription doctrines, and only 23% thought there was scientific evidence to
      prove homeopathy's effectiveness. Seeing homeopathy as a way to induce placebo
      effects had the strongest endorsement among prescribers and non-prescribers of
      homeopathy (63% and 74% endorsement respectively). Reimbursement of homeopathic
      remedies by statutory health insurance was rejected by 61% of all respondents.
      CONCLUSION: Medical specialties use homeopathy with significantly varying
      frequency and only half of the prescribers clearly intend to achieve specific
      effects. Moreover, the majority of prescribers acknowledge that effectiveness is
      unproven and give little importance to traditional principles behind homeopathy.
      Medical specialties and associated patient demands but also physicians' openness
      towards placebo interventions may play a role in homeopathy prescriptions.
      Education should therefore address not only the evidence base of homeopathy, but
      also ethical dilemmas with placebo interventions.

PMID- 29039628
TI  - Early versus late initiation of renal replacement therapy in patients with acute
      kidney injury: a meta-analysis of randomised clinical trials.
AB  - AIMS OF THE STUDY: The optimal timing of renal replacement therapy (RRT)
      initiation in acute kidney injury (AKI) remains a matter of debate. A systematic
      review and meta-analysis of randomised controlled trials (RCTs) was conducted to
      better estimate the effects of early initiation of RRT compared with late
      initiation of RRT among patients with AKI and in patients at risk for AKI.
      METHODS: A Medline literature research was conducted in PubMed for RCTs in adult
      patients with AKI that compared different RRT initiation strategies (early vs
      late). The meta-analysis outcomes were in-hospital or <=60 day mortality, and
      renal recovery. RESULTS: Nine trials meeting inclusion criteria and four trials
      investigating preventive dialysis in patients at risk for AKI were identified.
      Early initiation of RRT was not associated with reduced in-hospital or 60-day
      mortality: risk ratio (RR) 0.91, 95% confidence interval (CI) 0.72-1.16, p =
      0.46, I2 = 49%). When only the four trials that offered RRT within 6 to 12 hours
      of eligibility were included in the analysis, the results were similar (RR 0.93,
      95% CI 0.82-1.06) without significant heterogeneity. The percentage of patients
      among survivors who recovered enough kidney function to be off dialysis was
      similar with early compared with late RRT: RR 1.02, 95% CI 0.99-1.06, p = 0.16.
      Early initiation of RRT was associated with higher incidence of catheter-related
      infections: RR 1.82, 95% CI 1.03-3.21, p = 0.04. No survival benefit was
      identified in patients undergoing preventive dialysis: RR 0.85 (95% CI 0.52-1.41,
      p = 0.54). CONCLUSIONS: Early RRT in patients with AKI (or at risk for AKI) does
      not appear to provide a significant reduction in mortality rates compared with
      late RRT. The data did not suggest any apparent impact on renal recovery with
      early dialysis.

PMID- 29039629
TI  - Adolescents' contraception continuation in Switzerland: a prospective
      observational study.
AB  - BACKGROUND: Securing the adherence over time to contraception by adolescent girls
      is a challenge. Until now little was known about this topic in Switzerland. The
      aim of our study was to determine contraceptive continuation rates among
      adolescents in this country and assess possible predictive factors for
      discontinuation. METHODS: A prospective observational cohort study of 12- to 19
      year-old girls starting contraception was performed. Patients were interviewed
      again after 1 year by phone, email or postal mail. RESULTS: A total of 204
      patients were included, of whom 85.8% chose a combined oestrogen-progestogen
      pill. The answer rate 1 year later was 71%. Among these, continuation of the
      initially prescribed contraceptive method was observed in 73.1%. Factors
      statistically affecting the continuation rate were the initial contraceptive
      method, the place of residence and sexual activity after 1 year. Classification
      of contraceptive methods in decreasing order of continuation rate was the
      following: long acting reversible contraception (LARC) methods, oestrogen
      progestogen pills, injections, progestogen pills, patches and rings. Major
      reasons reported for stopping the prescribed contraceptive method were ending
      sexual relations (54.3%), developing side effects (34.3%) or changing to another
      contraceptive method (22.9%). Neither age, nationality, smoking, occupation, nor
      the legal representative's knowledge of the contraception influenced adherence.
      CONCLUSION: Contraceptive continuation rate was high among the adolescent
      population studied. The only predictive factor of discontinuation was the
      contraceptive method. Our study also reveals that respecting teenagers'
      confidentiality is essential as it does not negatively impact the continuation
      rate. The significant impact of the type of contraception on continuation rates
      stresses the importance of individualised counselling.

PMID- 29039631
TI  - Well-Being Hurts.

PMID- 29039630
TI  - Impairment of the chondrogenic phase of endochondral ossification in vivo by
      inhibition of cyclooxygenase-2.
AB  - Many studies have reported on the effects of cyclooxygenase-2 (COX-2) inhibition
      on osteogenesis. However, far less is known about the effects of COX-2 inhibition
      on chondrogenic differentiation. Previous studies conducted by our group show
      that COX-2 inhibition influences in vitro chondrogenic differentiation.
      Importantly, this might have consequences on endochondral ossification processes
      occurring in vivo, such as bone fracture healing, growth plate development and
      ectopic generation of cartilage. The goal of our study was to investigate, in
      vivo, the effect of COX-2 inhibition by celecoxib on the cartilaginous phase of
      three different endochondral ossification scenarios. 10 mg/kg/day celecoxib or
      placebo were orally administered for 25 d to skeletally-immature New Zealand
      White rabbits (n = 6 per group). Endochondral ossification during fracture
      healing of a non-critical size defect in the ulna, femoral growth plate and
      ectopically-induced cartilaginous tissue were examined by radiography, micro
      computed tomography (u-CT), histology and gene expression analysis. Celecoxib
      treatment resulted in delayed bone fracture healing, alterations in growth plate
      development and progression of mineralisation. In addition, chondrogenic
      differentiation of ectopically-induced cartilaginous tissue was severely impaired
      by celecoxib. In conclusion, we found that celecoxib impaired the chondrogenic
      phase of endochondral ossification.

PMID- 29039632
TI  - If Your Life Depended on It.

PMID- 29039633
TI  - Genetic Links Discovered For Facial Size and Shape.

PMID- 29039634
TI  - Researchers Push for Improved Treatment of Facial Pain.

PMID- 29039635
TI  - Bacteria Caused By Smokeless Tobacco Creates Health Issues.

PMID- 29039636
TI  - Shape of a Virus Changes When Invading a Host Cell.

PMID- 29039637
TI  - Peri-Implant Soft Tissue Augmentation in a Mild Smoker: A Surgical-Prosthetic
      Approach Using a Subepithelial CT Graft With Coronal Anchoring Sutures and a
      Zirconia Abutment.
AB  - This report presents the use of a CT graft to augment the periimplantsoft tissue
      at time of abutment placement in a smoker using coronalanchoring sutures around a
      zirconia abutment. Soft tissue augmentation at thetime of abutment connection,
      avoiding abutment removal after CT grafting, useof a zirconia abutment and
      placement of coronal anchoring sutures might be therecommended approach when
      dealing with such esthetic challenges.

PMID- 29039638
TI  - A Citywide Assessment of Oral Hygiene Needs of 5- to 7-Year-Old Children.
AB  - The purpose of this study was to assess the oral hygiene needs of
      6,957kindergarten and first-grade children enrolled in the San Bernardino City
      UnifiedSchool District. The findings from this study revealed that 9 percent of
      first-gradersdid not own a toothbrush, 15 percent shared a toothbrush and 25.3
      percent self-reportedmouth pain. In one school, 30 percent of the first-graders
      did not own atoothbrush and overall 38 percent of kindergarteners shared a
      toothbrush.

PMID- 29039639
TI  - Orthodontic Services Provided by Pediatric Dentists in California.
AB  - A survey was conducted in 2013 to document trends inorthodontic treatment
      provided by members of the California Society ofPediatric Dentistry (CSPD). A 21
      item survey was mailed to all activemembers of CSPD. Active members of CSPD spent
      less time and treatedfewer orthodontic conditions in their practice.

PMID- 29039640
TI  - High-Performance Ultraviolet-to-Infrared Broadband Perovskite Photodetectors
      Achieved via Inter-/Intraband Transitions.
AB  - A high-performance vertically injected broadband UV-to-IR photodetector based on
      Gd-doped ZnO nanorods (NRs)/CH3NH3PbI3 perovskite heterojunction was fabricated
      on metal substrates. Our perovskite-based photodetector is sensitive to a broad
      spectral range, from ultraviolet to infrared light region (lambda = 250-1357 nm).
      Such structure leads to a high photoresponsivity of 28 and 0.22 A/W, for white
      light and IR illumination, respectively, with high detectivity values of 1.1 *
      1012 and 9.3 * 109 Jones. Optical characterizations demonstrate that the IR
      detection is due to intraband transition in the perovskite material. Metal
      substrate boosts carrier injection, resulting in higher responsivity compared to
      the conventional devices grown on glass, whereas the presence of Gd increases the
      ZnO NRs performance. For the first time, the perovskite-based photodetector is
      demonstrated to extend its detection capability to IR (>1000 nm) with high room
      temperature responsivity across the detected spectrum, leading to a high
      performance ingenious cost-effective UV-to-IR broadband photodetector design for
      large-scale applications.

PMID- 29039641
TI  - Individual Nanoporous Carbon Spheres with High Nitrogen Content from
      Polyacrylonitrile Nanoparticles with Sacrificial Protective Layers.
AB  - Functional nanoporous carbon spheres (NPC-S) are important for applications
      ranging from adsorption, catalysis, separation to energy storage, and
      biomedicine. The development of effective NPC-S materials has been hindered by
      the fusion of particles during the pyrolytic process that results in agglomerated
      materials with reduced activity. Herein, we present a process that enables the
      scalable synthesis of dispersed NPC-S materials by coating sacrificial protective
      layers around polyacrylonitrile nanoparticles (PAN NPs) to prevent interparticle
      cross-linking during carbonization. In a first step, PAN NPs are synthesized
      using miniemulsion polymerization, followed by grafting of 3
      (triethoxysilyl)propyl methacrylate (TESPMA) to form well-defined core-shell
      structured PAN@PTESPMA nanospheres. The cross-linked PTESPMA brush layer
      suppresses cross-linking reactions during carbonization. Uniform NPC-S exhibiting
      diameters of ~100 nm, with relatively high accessible surface area (~424 m2/g),
      and high nitrogen content (14.8 wt %) was obtained. When compared to a regular
      nanoporous carbon monolith (NPC-M), the nitrogen-doped NPC-S demonstrated better
      performance for CO2 capture with a higher CO2/N2 selectivity, an increased
      efficiency in catalytic oxygen reduction reactions, as well as improved
      electrochemical capacitive behavior. This miniemulsion polymerization-based
      strategy for the preparation of functional PAN NPs provides a new, facile
      approach to prepare high-performance porous carbon spheres for diverse
      applications.

PMID- 29039642
TI  - Self-Powered Nanocomposites under an External Rotating Magnetic Field for
      Noninvasive External Power Supply Electrical Stimulation.
AB  - Electrical stimulation in biology and gene expression has attracted considerable
      attention in recent years. However, it is inconvenient that the electric
      stimulation needs to be supplied an implanted power-transported wire connecting
      the external power supply. Here, we fabricated a self-powered composite nanofiber
      (CNF) and developed an electric generating system to realize electrical
      stimulation based on the electromagnetic induction effect under an external
      rotating magnetic field. The self-powered CNFs generating an electric signal
      consist of modified MWNTs (m-MWNTs) coated Fe3O4/PCL fibers. Moreover, the output
      current of the nanocomposites can be increased due to the presence of the
      magnetic nanoparticles during an external magnetic field is applied. In this
      paper, these CNFs were employed to replace a bullfrog's sciatic nerve and to
      realize the effective functional electrical stimulation. The cytotoxicity assays
      and animal tests of the nanocomposites were also used to evaluate the
      biocompatibility and tissue integration. These results demonstrated that this
      self-powered CNF not only plays a role as power source but also can act as an
      external power supply under an external rotating magnetic field for noninvasive
      the replacement of injured nerve.

PMID- 29039643
TI  - Exploring the pH Sensitivity of Poly(allylamine) Phosphate Supramolecular
      Nanocarriers for Intracellular siRNA Delivery.
AB  - Silencing RNA (siRNA) technologies emerge as a promising therapeutic tool for the
      treatment of multiple diseases. An ideal nanocarrier (NC) for siRNAs should be
      stable at physiological pH and release siRNAs in acidic endosomal pH, fulfilling
      siRNA delivery only inside cells. Here, we show a novel application of polyamine
      phosphate NCs (PANs) based on their capacity to load negatively charged nucleic
      acids and their pH stability. PANs are fabricated by complexation of phosphate
      anions from phosphate buffer solution (PB) with the amine groups of
      poly(allylamine) hydrochloride as carriers for siRNAs. PANs are stable in a
      narrow pH interval, from 7 to 9, and disassemble at pH's higher than 9 and lower
      than 6. siRNAs are encapsulated by complexation with poly(allylamine)
      hydrochloride before or after PAN formation. PANs with encapsulated siRNAs are
      stable in cell media. Once internalized in cells following endocytic pathways,
      PANs disassemble at the low endosomal pH and release the siRNAs into the
      cytoplasm. Confocal laser scanning microscopy (CLSM) images of Rhodamine Green
      labeled PANs (RG-PANs) with encapsulated Cy3-labeled siRNA in A549 cells show
      that siRNAs are released from the PANs. Colocalization experiments with labeled
      endosomes and either labeled siRNAs prove the translocation of siRNAs into the
      cytosol. As a proof of concept, it is shown that PANs with encapsulated green
      fluorescence protein (GFP) siRNAs silence GFP in A549 cells expressing this
      protein. Silencing efficacy was evaluated by flow cytometry, CLSM, and Western
      blot assays. These results open the way for the use of poly(allylamine) phosphate
      nanocarriers for the intracellular delivery of genetic materials.

PMID- 29039644
TI  - Laponite-Based Surfaces with Holistic Self-Cleaning Functionality by Combining
      Antistatics and Omniphobicity.
AB  - In the present work, perfluoroalkylated laponite nanoparticles with a high degree
      of functionalization (60 wt %) have been prepared and a methodology to prepare
      transparent, antistatic, and omniphobic laponite-based films with holistic self
      cleaning properties against liquids, solids and liquid-solid mixtures has been
      developed. The intrinsic electrical and ionic conductivities observed in
      unmodified laponite coatings are combined with perfluoroalkyl-modified laponite
      clays. As a result, films with improved self-cleaning functionality based on dust
      repellency and omniphobic liquid-repellence (sheet resistance in the range of 107
      Omega/? and contact angles of 106 degrees  (H2O) and 93 degrees  (oil)) were
      obtained. These unique films, being capable to repel dust and liquids, were
      applied to a variety of substrates (i.e., glass and plastics) and tested against
      solids and liquids of different nature with excellent performance. Bending tests
      of these holistic self-cleaning films deposited over flexible substrates showed
      better mechanical performance than unmodified laponite films.

PMID- 29039645
TI  - Blue Quantum Dot Light-Emitting Diodes with High Electroluminescent Efficiency.
AB  - High-efficiency blue CdSe/ZnS quantum dots (QDs) have been synthesized for
      display application with emission peak over 460 nm with the purpose of reducing
      the harmful effect of short-wavelength light to human eyes. To reach a better
      charge balance, different size ZnO nanoparticles (NPs) were synthesized and
      electrical properties of ZnO NPs were analyzed. Quantum dot light-emitting diodes
      (QLEDs) based on as-prepared blue QDs and optimized ZnO NPs have been
      successfully fabricated. Using small-size ZnO NPs, we have obtained a maximum
      current efficiency (CE) of 14.1 cd A-1 and a maximum external quantum efficiency
      (EQE) of 19.8% for QLEDs with an electroluminescence (EL) peak at 468 nm. To the
      best of our knowledge, this EQE is the highest value in comparison to the
      previous reports. The CIE 1931 color coordinates (0.136, 0.078) of this device
      are quite close to the standard (0.14, 0.08) of National Television System
      Committee (NTSC) 1953. The color saturation blue QLEDs show great promise for use
      in next-generation full-color displays.

PMID- 29039646
TI  - Proteomics-Based Tools for Evaluation of Cell-Free Protein Synthesis.
AB  - Cell-free protein synthesis (CFPS) has the potential to produce enzymes,
      therapeutic agents, and other proteins, while circumventing difficulties
      associated with in vivo heterologous expression. However, the contents of the
      cell-free extracts used to carry out synthesis are generally not characterized,
      which hampers progress toward enhancing yield or functional activity of the
      target protein. We explored the utility of mass spectrometry (MS)-based
      proteomics for characterizing the bacterial extracts used for transcribing and
      translating gene sequences into proteins as well as the products of CFPS
      reactions. Full proteome experiments identified over 1000 proteins per reaction.
      The complete set of proteins necessary for transcription and translation were
      found, demonstrating the ability to define potential metabolic capabilities of
      the extract. Further, MS-based techniques allowed characterization of the CFPS
      product and provided insight into the synthesis reaction and potential functional
      activity of the product. These capabilities were demonstrated using two different
      CFPS products, the commonly used standard green fluorescent protein (GFP, 27 kDa)
      and the polyketide synthase DEBS1 (394 kDa). For the large, multidomain DEBS1,
      substantial premature termination of protein translation was observed.
      Additionally, MS/MS analysis, as part of a conventional full proteomics workflow,
      identified post-translational modifications, including the chromophore in GFP, as
      well as the three phosphopantetheinylation sites in DEBS1. A hypothesis-driven
      approach focused on these three sites identified that all were correctly modified
      for DEBS1 expressed in vivo but with less complete coverage for protein expressed
      in CFPS reactions. These post-translational modifications are essential for
      functional activity, and the ability to identify them with mass spectrometry is
      valuable for judging the success of the CFPS reaction. Collectively, the use of
      MS-based proteomics will prove advantageous for advancing the application of CFPS
      and related techniques.

PMID- 29039647
TI  - Co Nanoparticles Encapsulated in N-Doped Carbon Nanosheets: Enhancing Oxygen
      Reduction Catalysis without Metal-Nitrogen Bonding.
AB  - It is known that introducing metal nanoparticles (e.g., Fe and Co) into N-doped
      carbons can enhance the activity of N-doped carbons toward the oxygen reduction
      reaction (ORR). However, introducing metals into N-doped carbons inevitably
      causes the formation of multiple active sites. Thus, it is challenging to
      identify the active sites and unravel mechanisms responsible for enhanced ORR
      activity. Herein, by developing a new N-heterocyclic carbene (NHC)-Co complex as
      the nitrogen- and metal-containing precursor, we report the synthesis of N-doped
      carbon nanosheets embedded with Co nanoparticles as highly active ORR catalysts
      without direct metal-nitrogen bonding. Electrochemical measurements and X-ray
      absorption spectroscopy indicate that the carbon-nitrogen sites surrounding Co
      nanoparticles are responsible for the observed ORR activity and stability.
      Density functional theory calculations further reveal that Co nanoparticles could
      facilitate the protonation of O2 and thus promote the ORR activity. These results
      provide new prospects in the rational design and synthesis of heteroatom-doped
      carbon materials as non-precious-metal catalysts for various electrochemical
      reactions.

PMID- 29039648
TI  - Modular Elastomer Photoresins for Digital Light Processing Additive
      Manufacturing.
AB  - A series of photoresins suitable for the production of elastomeric objects via
      digital light processing additive manufacturing are reported. Notably, the
      printing procedure is readily accessible using only entry-level equipment under
      ambient conditions using visible light projection. The photoresin formulations
      were found to be modular in nature, and straightforward adjustments to the resin
      components enabled access to a range of compositions and mechanical properties.
      Collectively, the series includes silicones, hydrogels, and hybrids thereof.
      Printed test specimens displayed maximum elongations of up to 472% under tensile
      load, a tunable swelling behavior in water, and Shore A hardness values from 13.7
      to 33.3. A combination of the resins was used to print a functional multimaterial
      three-armed pneumatic gripper. These photoresins could be transformative to
      advanced prototyping applications such as simulated human tissues, stimuli
      responsive materials, wearable devices, and soft robotics.

PMID- 29039650
TI  - Programmed Nanococktail Based on pH-Responsive Function Switch for Self
      Synergistic Tumor-Targeting Therapy.
AB  - Tumor-targeting combination chemotherapy is an important way to improve the
      therapeutic index and reduce the side effects as compared to traditional cancer
      treatments. However, one of the major challenges in surface functionalization of
      nanoparticle (NP) is accomplishing multiple purposes through one single ligand.
      Upon such consideration, methotrexate (MTX), an anticancer drug with a targeting
      moiety inspired by the similar structure of folate, could be used to covalently
      link with lipid-polymer conjugate (DSPE-PEG) via a pH-sensitive dynamic covalent
      imine (CH?N) bond to synthesize the acid-induced function "targeting-anticancer"
      switching DSPE-PEG-CH?N-MTX. We hypothesize that using this kind of MTX prodrug
      to functionalize NP's surface would be conductive to combine the early phase
      active targeting function and the late-phase anticancer function in one
      nanosystem. Herein, a nanococktail is programmed for codelivery of epirubicin
      (EPI) and MTX by co-self-assembly of acid-dissociated EPI-phospholipid (PC)
      complex and acid-cleavable DSPE-PEG-CH?N-MTX conjugate. The obtained nanococktail
      (MTX-PEG-EPI-PC NPs) could not only actively target folate receptors
      overexpressing tumor cells but also respond to acidic endo/lysosomes for
      triggering the on-demand release of pharmaceutically active EPI/MTX. The
      intracellular drug distribution also demonstrated that the system could codeliver
      two drugs to individual target sites of action, inducing the significant
      synergistic anticancer efficiency based on different anticancer mechanisms. More
      importantly, the in vivo tumor accumulation and anticancer efficacy of MTX-PEG
      EPI-PC NPs (via cleavable imine bond) were significantly enhanced as compared to
      the individual free drug, both free drugs, PEG-EPI-PC NPs, and MTX-PEG-EPI-PC NPs
      (via the uncleavable amide bond). This self-synergistic tumor-targeting therapy
      might represent a promising strategy for cancer treatment.

PMID- 29039649
TI  - Comparative Membrane Proteomics Reveals a Nonannotated E. coli Heat Shock
      Protein.
AB  - Recent advances in proteomics and genomics have enabled discovery of thousands of
      previously nonannotated small open reading frames (smORFs) in genomes across
      evolutionary space. Furthermore, quantitative mass spectrometry has recently been
      applied to analysis of regulated smORF expression. However, bottom-up proteomics
      has remained relatively insensitive to membrane proteins, suggesting they may
      have been underdetected in previous studies. In this report, we add biochemical
      membrane protein enrichment to our previously developed label-free quantitative
      proteomics protocol, revealing a never-before-identified heat shock protein in
      Escherichia coli K12. This putative smORF-encoded heat shock protein, GndA, is
      likely to be ~36-55 amino acids in length and contains a predicted transmembrane
      helix. We validate heat shock-regulated expression of the gndA smORF and
      demonstrate that a GndA-GFP fusion protein cofractionates with the cell membrane.
      Quantitative membrane proteomics therefore has the ability to reveal nonannotated
      small proteins that may play roles in bacterial stress responses.

PMID- 29039651
TI  - Intracellular Drug Uptake-A Comparison of Single Cell Measurements Using ToF-SIMS
      Imaging and Quantification from Cell Populations with LC/MS/MS.
AB  - ToF-SIMS is a label-free imaging method that has been shown to enable imaging of
      amiodarone in single rat macrophage (NR8383) cells. In this study, we show that
      the method extends to three other cell lines relevant to drug discovery: human
      embryonic kidney (HEK293), cervical cancer (HeLa), and liver cancer (HepG2).
      There is significant interest in the variation of drug uptake at the single cell
      level, and we use ToF-SIMS to show that there is great diversity between
      individual cells and when comparing each of the cell types. These single cell
      measurements are compared to quantitative measurements of cell-associated
      amiodarone for the population using LC/MS/MS and cell counting with flow
      cytometry. NR8383 and HepG2 cells uptake the greatest amount of amiodarone with
      an average of 2.38 and 2.60 pg per cell, respectively, and HeLa and Hek 293 have
      a significantly lower amount of amiodarone at 0.43 and 0.36 pg per cell,
      respectively. The amount of cell-associated drug for the ensemble population
      measurement (LC/MS/MS) is compared with the ToF-SIMS single cell data: a similar
      amount of drug was detected per cell for the NR8383, and HepG2 cells at a greater
      level than that for the HEK293 cells. However, the two techniques did not agree
      for the HeLa cells, and we postulate potential reasons for this.

PMID- 29039652
TI  - Insights into Cotranslational Membrane Protein Insertion by Combined LILBID-Mass
      Spectrometry and NMR Spectroscopy.
AB  - Cotranslational insertion of membrane proteins into defined nanoparticle
      membranes has been developed as an efficient process to produce highly soluble
      samples in native-like environments and to study lipid-dependent effects on
      protein structure and function. Numerous examples of the structural and
      functional characterization of transporters, ion channels, or G-protein-coupled
      receptors in cotranslationally formed nanodisc complexes demonstrate the
      versatility of this approach, although the basic underlying mechanisms of
      membrane insertion are mainly unknown. We have revealed the first aspects of the
      insertion of proteins into nanodiscs by combining cell-free expression,
      noncovalent mass spectrometry, and NMR spectroscopy. We provide evidence of
      cooperative insertion of homo-oligomeric complexes and demonstrate the
      possibility to modulate their stoichiometry by modifying reaction conditions.
      Additionally, we show that significant amounts of lipid are released from the
      nanodiscs upon insertion of larger protein complexes.

PMID- 29039653
TI  - Boric Acid Induced Transient Cross-Links in Lactose-Modified Chitosan (Chitlac).
AB  - The present paper explores the effect of boric acid on Chitlac, a lactose
      modified chitosan which had previously shown interesting biological and physical
      chemical features. The herewith-reported experimental evidences demonstrated that
      boric acid binds to Chitlac, producing conformational and association effects on
      the chitosan derivative. The thermodynamics of boric acid binding to Chitlac was
      explored by means of 11B NMR, circular dichroism (CD), and UV-vis spectroscopy,
      while macromolecular effects were investigated by means of viscometry and dynamic
      light scattering (DLS). The experimental results revealed a chain-chain
      association when limited amounts of boric acid were added to Chitlac. However,
      upon exceeding a critical boric acid limit dependent on the polysaccharide
      concentration, the soluble aggregates disentangle. The rheological behavior of
      Chitlac upon treatment with boric acid was explored showing a dilatant behavior
      in conditions of steady flow. An uncommonly high dependence in the scaling law
      between the zero-shear viscosity and the concentration of Chitlac was found,
      i.e., eta0 ? CCTL5.8, pointing to interesting potential implications of the
      present system in biomaterials development.

PMID- 29039654
TI  - A Bottom-Up Synthesis of Vinyl-Cellulose Nanosheets and Their Nanocomposite
      Hydrogels with Enhanced Strength.
AB  - Extracted nanocellulose from natural resources commonly requires modification
      before it is used as an effective nanofiller. In the present study, through an
      enzymatic polymerization of alpha-d-glucose 1-phosphate from the primer 2
      (glucosyloxy)ethyl methacrylate (GEMA), a novel type of two-dimensional
      methacrylate-containing cellulose nanosheets (CNS) with a thickness of about 6
      nm, named as GEMA-CNS, was directly synthesized under a mild condition by a
      "bottom-up" method. The structure and morphology of GEMA-CNS were characterized
      by 1H-nuclear magnetic resonance (NMR), matrix-assisted laser
      desorption/ionization time-of-flight mass spectra (MALDI-TOF MS), Fourier
      transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission
      electron microscopy (TEM), and atomic force microscopy (AFM). Afterward, the
      obtained GEMA-CNS was covalently incorporated into poly(ethylene glycol) matrix
      through thiol-ene Michael addition, fabricating a series of GEMA-CNS-based
      nanocomposite hydrogels. The addition of GEMA-CNS effectively improved the
      mechanical strength and altered the internal network structures of hydrogels;
      additionally, the swelling/biodegradation behaviors of gels in phosphate buffer
      saline (pH 7.4) at 37  degrees C were affected to some degree. This species of
      property-tunable hydrogels with GEMA-CNS dosage demonstrates potential
      applications in tissue engineering. The current presentation opens a new road for
      direct enzymatic preparation of reactive nanocellulose and its novel applications
      in nanocomposite materials.

PMID- 29039655
TI  - Dimerization and Long-Range Repulsion Established by Both Termini of the
      Microtubule-Associated Protein Tau.
AB  - Tau is a microtubule-associated protein found in neuronal axons that has several
      well-known functions, such as promoting microtubule polymerization, stabilizing
      microtubules against depolymerization, and spatially organizing microtubules in
      axons. Two contrasting models have been previously described to explain tau's
      ability to organize the spacing between microtubules: complementary dimerization
      of the projection domains of taus on adjacent microtubules or tau's projection
      domain acting as a polyelectrolyte brush. In this study, atomic force microscopy
      was used to interrogate intermolecular interactions between layers of tau protein
      immobilized on mica substrates and on silicon nitride atomic force microscope
      tips. On these surfaces, tau adopts an orientation comparable to that when bound
      to microtubules, with the basic microtubule binding domain immobilized and the
      acidic domains extending into solution. Force-distance curves collected via
      atomic force microscopy reveal that full length human tau, when assembled into
      dense surface-bound layers, can participate in attractive electrostatic
      interactions consistent with the previously reported dimerization model. However,
      modulating the ionic strength of the surrounding solution can change the
      structure of these layers to produce purely repulsive interactions consistent
      with a polyelectrolyte brush structure, thus providing biophysical evidence to
      support both the zipper and brush models. In addition, a pair of projection
      domain deletion mutants were examined to investigate whether the projection
      domain of the protein is essential for the dimerization and brush models. Force
      distance curves collected on layers of these proteins demonstrate that the C
      terminus can play a role analogous to that of the projection domain.

PMID- 29039656
TI  - Highly Symmetric AB2 Framework Related to Tridymite in the Disordered
      Nitridosilicate La24Sr14-7x[Si36N72](O1-xFx)14 (x = 0.489).
AB  - La24Sr14-7x[Si36N72](O1-xFx)14 with x = 0.489 was obtained as a microcrystalline
      product by metathesis at 1500  degrees C in a radio-frequency furnace starting
      from Si(NH)2, La(NH2)3, SrH2, LaF3, and CeF3. The structure of the new
      nitridosilicate oxide fluoride was determined by combining transmission electron
      microscopy (TEM) and single-crystal X-ray diffraction using a microfocused
      synchrotron beam. The structure model with pronounced disorder [P63/mmc, Z = 1, a
      = 16.2065(3), c = 9.4165(1) A, R1(obs) = 0.0436] was confirmed by electron
      diffraction and aberration-corrected Z-contrast scanning TEM. The highly
      symmetric AB2 framework, which was theoretically predicted but not yet realized,
      consists of all-side vertex-sharing SiN4 tetrahedra that form channels along
      [001] filled with La, Sr, O, and F atoms. The connectivity pattern is related to
      that of tridymite. X-ray spectroscopy and bond-valence-sum calculations were
      further taken into account for assignment of the N, O, and F atoms.

PMID- 29039657
TI  - Ternary Inorganic Compounds Containing Carbon, Nitrogen, and Oxygen at High
      Pressures.
AB  - Ternary CxNyOz compounds are actively researched as novel high energy density and
      ultrahard materials. Although some synthesis work has been performed at ambient
      conditions, very little is known about the high pressure chemistry of of CxNyOz
      compounds. In this work, first-principles variable-composition evolutionary
      structure prediction calculations are performed with the goal of discovering
      novel mixed CxNyOz materials at ambient and high pressure conditions. By
      systematically searching ternary variable composition crystalline materials, the
      full ternary phase diagram is constructed in the range of pressures from 0 to 100
      GPa. The search finds the C2N2O crystal containing an extended covalent network
      of C, N, and O atoms, having space group symmetry Cmc21, and stable above just 10
      GPa. Several other novel metastable (CO)x-(N)y crystalline compounds discovered
      during the search, including two polymorphs of C2NO2 and two polymorphs of C3N2O3
      crystals, are found to be energetically favorable compared to polymeric carbon
      monoxide (CO) and nitrogen. Predicted new compounds are characterized by their
      Raman spectra and equations of state.

PMID- 29039659
TI  - Nine-Membered Benzofuran-Fused Heterocycles: Enantioselective Synthesis by Pd
      Catalysis and Rearrangement via Transannular Bond Formation.
AB  - The first enantioselective formal [5+4] cycloaddition is realized under palladium
      catalysis to deliver benzofuran-fused nine-membered rings. These medium-sized
      heterocycles and derivatives undergo unique rearrangements induced by
      transannular bond formation, resulting in the production of two classes of
      densely substituted polycyclic heterocycles in excellent efficiency and
      stereoselectivity.

PMID- 29039658
TI  - Membrane Binding and Pore Formation by a Cytotoxic Fragment of Amyloid beta
      Peptide.
AB  - Amyloid beta (Abeta) peptide contributes to Alzheimer's disease by a yet
      unidentified mechanism. In the brain tissue, Abeta occurs in various forms,
      including an undecapeptide Abeta25-35, which exerts a neurotoxic effect through
      the mitochondrial dysfunction and/or Ca2+-permeable pore formation in cell
      membranes. This work was aimed at the biophysical characterization of membrane
      binding and pore formation by Abeta25-35. Interaction of Abeta25-35 with anionic
      and zwitterionic membranes was analyzed by microelectrophoresis. In pore
      formation experiments, Abeta25-35 was incubated in aqueous buffer to form
      oligomers and added to Quin-2-loaded vesicles. Gradual increase in Quin-2
      fluorescence was interpreted in terms of membrane pore formation by the peptide,
      Ca2+ influx, and binding to intravesicular Quin-2. The kinetics and magnitude of
      this process were used to evaluate the rate constant of pore formation, peptide
      peptide association constants, and the oligomeric state of the pores. Decrease in
      membrane anionic charge and high ionic strength conditions significantly
      suppressed membrane binding and pore formation, indicating the importance of
      electrostatic interactions in these events. Circular dichroism spectroscopy
      showed that Abeta25-35 forms the most efficient pores in beta-sheet conformation.
      The data are consistent with an oligo-oligomeric pore model composed of up to
      eight peptide units, each containing 6-8 monomers.

PMID- 29039660
TI  - Iron-Catalyzed Regioselective Anti-Markovnikov Addition of C-H Bonds in Aromatic
      Ketones to Alkenes.
AB  - We report here on a C-H alkylation reaction, in which the coupling of aromatic
      ketones with alkenes proceeds in the presence of only a simple Fe(PMe3)4
      catalyst. The anti-Markovnikov addition of ortho C-H bonds in various ketones
      occurs with excellent regioselectivity under relatively mild reaction conditions.
      A strikingly wide variety of alkenes can be used for this reaction, and the high
      yielding anti-Markovnikov addition of aromatic C-H bonds to enol ethers was
      achieved for the first time using this catalyst system.

PMID- 29039661
TI  - Rhodium/Copper Cocatalyzed Highly trans-Selective 1,2-Diheteroarylation of
      Alkynes with Azoles via C-H Addition/Oxidative Cross-Coupling: A Combined
      Experimental and Theoretical Study.
AB  - Transition metal-catalyzed addition of diaryl alkynes with arylating reagents for
      the synthesis of tetraarylethylenes generally encounters rigorous reaction
      conditions and relies on the use of prefunctionalized substrates such as organic
      halides or surrogates and organometallic reagents. In this work, we establish a
      highly trans-selective 1,2-diheteroarylation of alkynes with azoles via a
      rhodium/copper cocatalyzed C-H addition/oxidative coupling process. Moreover, the
      diheteroarylation developed herein could open a door for the synthesis of
      heteroarene-doped tetraarylethylenes, and the photoluminescence (PL) spectra in
      THF-water mixtures and solid powder verify that these tetra(hetero)arylethylenes
      are aggregation-induced emission (AIE) active, building a new AIE molecule
      library. With a combination of experimental and theoretical methods, the reaction
      mechanism for addition/oxidative cross-coupling of internal alkynes with azoles
      has been investigated. Theoretical calculations reveal that the
      metalation/deprotonation of azole could occur with either rhodium or copper
      species. When azolylrhodium is formed, an alkyne could insert into the Rh-C bond.
      Another azolyl group could then transfer to rhodium from azolylcopper compound.
      The subsequent intramolecular trans-nucleophilic addition generates the second C
      C bond. Meanwhile, the putative pathway for the formation of the
      hydroheteroarylated byproduct has also been explained by theoretical
      calculations.

PMID- 29039662
TI  - Quest for Novel Chemical Entities through Incorporation of Silicon in Drug
      Scaffolds.
AB  - In order to optimize a lead molecule for further development, bioisosteric
      replacements are generally adopted as one of the strategies. Silicon appears to
      be the right choice as a carbon isostere because of the similarity in chemical
      properties. Silicon can be strategically introduced in a molecule to modulate its
      druglike properties, providing medicinal chemists with an unconventional strategy
      for replacing a carbon atom. Silicon can also be introduced to replace other
      heteroatoms and can act as a surrogate of functional groups such as olefin and
      amide as well. The present Perspective focuses on the opportunities that silicon
      incorporation offers in drug discovery, with an emphasis on case studies where
      introduction of silicon has created a benefit over its analog. We have tried to
      highlight all the recent developments in the field and briefly discuss the
      challenges associated with them.

PMID- 29039663
TI  - Structural Dynamics of Al2O3/NiAl(110) During Film Growth in NO2.
AB  - While continuum descriptions of oxide film growth are well established, the local
      structural dynamics during oxide growth are largely unexplored. Here, we
      investigate this using scanning tunneling microscopy (STM) and X-ray
      photoelectron spectroscopy (XPS) for the example of alumina film growth on
      NiAl(110) following NO2 exposure. To maintain a well-defined system, we have
      adopted a cyclic growth approach of NO2 adsorption and annealing. NO2 adsorption
      at 693 K results in the formation of a vacancy island pattern in the NiAl(110)
      substrate, which is filled with AlOx by diffusion of O through the alumina film.
      The patches of AlOx coalesce to form smooth terraces upon annealing to 1200 K. By
      repeated cycling, we have grown films of up to 0.9 nm thick. While peak shifts in
      the XPS spectra indicate that the film maintains its insulating character upon
      thickening, our STM data show that there is a finite density of states within the
      band gap. The thickening of the alumina film is accompanied by the formation of
      trenches in the surface, which we interpret to be the result of film stress
      relief.

PMID- 29039664
TI  - Stereocontrolled Semisyntheses of Elliptone and 12abeta-Hydroxyelliptone.
AB  - Operationally simple, stereocontrolled semisyntheses of the anticancer rotenoids
      elliptone and 12abeta-hydroxyelliptone, isolated from Derris elliptica and Derris
      trifoliata, respectively, are described. Inspired by the work of Singhal,
      elliptone was prepared from rotenone via a dihydroxylation-oxidative cleavage,
      chemoselective Baeyer-Villiger oxidation, and acid-catalyzed elimination
      sequence. Elaboration of elliptone to 12abeta-hydroxyelliptone was achieved via a
      diastereoselective chromium-mediated Etard-like hydroxylation. The semisynthesis
      of elliptone constitutes an improvement over previous methods in terms of safety,
      scalability, and yield, while the first synthesis of 12abeta-hydroxyelliptone is
      also described.

PMID- 29039665
TI  - Discontinuity in Fast Dynamics at the Glass Transition of ortho-Terphenyl.
AB  - The dynamics of the molecular glass former ortho-terphenyl through the glass
      transition were observed with two-dimensional infrared vibrational spectroscopy
      measurements of spectral diffusion using the small probe molecule
      phenylselenocyanate. Although the slow diffusive motions were not visible on the
      experimental time scale, a picosecond-scale exponential relaxation was observed
      at temperatures from above to well below the glass transition temperature. The
      characteristic time scale has a smooth temperature dependence from the liquid
      into the glass phase, but the range of vibrational frequencies the probe samples
      displayed a discontinuity at the glass transition temperature. Complementary pump
      probe experiments associate the observed motion with density fluctuations. The
      key features of the dynamics are reproduced with a simple corrugated well
      potential energy surface model. In addition, the temperature dependence of the
      homogeneous vibrational dephasing was found to have a T2 functional form, where T
      is the absolute temperature.

PMID- 29039666
TI  - Comparative Assessment of Computational Methods for Free Energy Calculations of
      Ionic Hydration.
AB  - Experimental observations for ionic hydration free energies are highly debated
      mainly due to the ambiguous absolute hydration free energy of proton,
      DeltaGhyd*(H+). Hydration free energies (HFEs) of the 112 singly charged ions in
      the Minnesota solvation database were predicted by six methods with explicit and
      implicit solvent models, namely, thermodynamic integration (TI), energy
      representation module (ERmod), three-dimensional reference interaction site model
      (3D-RISM), and continuum solvation models based on the quantum mechanical charge
      density (SMD) and on the Poisson-Boltzmann (PB) and generalized Born (GB)
      theories. Taking the solvent Galvani potential of water into account, the
      resulting real HFEs from TI calculations for the generalized Amber force field
      (GAFF) modeled ions best match the experiments based on DeltaGhyd*(H+) = -262.4
      kcal/mol (Randles Trans. Faraday Soc . 1956 , 52 , 1573 - 1581 ), in agreement
      with our previous work on charged amino acids (Zhang et al. J. Phys. Chem. Lett.
      2017 , 8 , 2705 - 2712 ). The examined computational methods show an accuracy of
      ~7 kcal/mol for the GAFF-modeled ions, except for SMD with a higher accuracy of
      ~4 kcal/mol. A biased deficiency in modeling anionic compounds by GAFF is
      observed with a larger standard deviation (SD) of 9 kcal/mol than that for
      cations (SD ~ 4 kcal/mol). The relatively cheap ERmod and 3D-RISM methods
      reproduce TI results with good accuracy, although ERmod yields a systematic
      underestimation for cations by 9 kcal/mol; PB and GB generate relative (but not
      absolute) HFEs comparable to the TI predictions. Computational accuracy is found
      to be more limited by the accuracy of force fields rather than the models
      themselves.

PMID- 29039667
TI  - Pretreatment with Phytochemicals To Reduce Secondary Effects of Traumatic Brain
      Injury.

PMID- 29039668
TI  - Targets for Drug Therapy for Autism Spectrum Disorder: Challenges and Future
      Directions.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by
      persistent deficits in social communication and interaction and restricted,
      repetitive patterns of behavior, interests, and activities. Various factors are
      involved in the etiopathogenesis of ASD, including genetic factors, environmental
      toxins and stressors, impaired immune responses, mitochondrial dysfunction, and
      neuroinflammation. The heterogeneity in the phenotype among ASD patients and the
      complex etiology of the condition have long impeded the advancement of the
      development of pharmacological therapies. In the recent years, the integration of
      findings from mouse models to human genetics resulted in considerable progress
      toward the understanding of ASD pathophysiology. Currently, strategies to treat
      core symptoms of ASD are directed to correct synaptic dysfunctions, abnormalities
      in central oxytocin, vasopressin, and serotonin neurotransmission, and
      neuroinflammation. Here, we present a survey of the studies that have suggested
      molecular targets for drug development for ASD and the state-of-the-art of
      medicinal chemistry efforts in related areas.

PMID- 29039670
TI  - Proton-Exchange-Induced Configuration Rearrangement in a Poly(ionic liquid)
      Solution: A NMR Study.
AB  - Polymeric ionic liquids have emerged recently as a promising alternative to
      traditional polymers as the polymer electrolyte membrane materials of choice
      because of their strongly decoupled dynamics between the polymer backbone and the
      counterions. Knowledge of proton exchange and transport mechanism in such
      materials is critical to the design and development of new poly(ionic liquid)
      materials with improved electrochemical properties. Our NMR results show that the
      proton exchange between the labile proton of the diethylmethylammonium (NH122)
      cation and H2O molecules is accompanied by a concerted configuration
      rearrangement of the ammonium. Through a combination of PFG-NMR and proton
      relaxation (line width) analysis, we demonstrate that at lower temperatures the
      labile proton diffuses along with the NH122 ammonium cation as an integral unit,
      whereas at higher temperatures the NH/H2O proton exchange sets in gradually, and
      the PFG-NMR measured diffusion coefficient is a population-averaged value between
      the two exchanging sites.

PMID- 29039671
TI  - N-Methylation of Amines with Methanol Catalyzed by a Cp*Ir Complex Bearing a
      Functional 2,2'-Bibenzimidazole Ligand.
AB  - A new type of Cp*Ir complex bearing a functional 2,2'-bibenzimidazole ligand was
      designed, synthesized, and found to be a highly effective and general catalyst
      for the N-methylation of a variety of amines with methanol in the presence of a
      weak base (0.3 equiv of Cs2CO3).

PMID- 29039672
TI  - Stereoselective Epimerizations of Glycosyl Thiols.
AB  - Glycosyl thiols are widely used in stereoselective S-glycoside synthesis. Their
      epimerization from 1,2-trans to 1,2-cis thiols (e.g., equatorial to axial
      epimerization in thioglucopyranose) was attained using TiCl4, while SnCl4
      promoted their axial-to-equatorial epimerization. The method included application
      for stereoselective beta-d-manno- and beta-l-rhamnopyranosyl thiol formation.
      Complex formation explains the equatorial preference when using SnCl4, whereas
      TiCl4 can shift the equilibrium toward the 1,2-cis thiol via 1,3-oxathiolane
      formation.

PMID- 29039669
TI  - Experimental and Computational Gas Phase Acidities of Conjugate Acids of
      Triazolylidene Carbenes: Rationalizing Subtle Electronic Effects.
AB  - In recent years, triazolylidene carbenes have come to the forefront as important
      organocatalysts for a wide range of reactions. The fundamental properties of
      these species, however, remain largely unknown. Herein, the gas phase acidities
      have been measured and calculated for a series of triazolium cations (the
      conjugate acids of the triazolylidene carbenes) that have not been heretofore
      examined in vacuo. The results are discussed in the context of these species as
      catalysts. We find correlations between the gas phase acidity and selectivity in
      two Umpolung reactions catalyzed by these species; such correlations are the
      first of their kind. We are able to use these linear correlations to improve
      reaction enantioselectivity. These results establish the possibility of using
      these thermochemical properties to predict reactivity in related transformations.

PMID- 29039673
TI  - Rapid Access to a Broad Range of 6'-Substituted Firefly Luciferin Analogues
      Reveals Surprising Emitters and Inhibitors.
AB  - Light-emitting firefly luciferin analogues contain electron-donating groups in
      the 6'-position, but the scope of known 6'-substitution remains narrow. A two
      step route to a broad range of 6'-substituted luciferin analogues was developed
      to fill this void and enable more extensive study of the 6'-functionality. This
      chemistry allowed direct access to "caged" amide and bright azetidine analogues,
      but also revealed thioether inhibitors and unexpectedly luminogenic aryl amine
      derivatives.

PMID- 29039674
TI  - Spin-Charge Separation in Finite Length Metallic Carbon Nanotubes.
AB  - Using time-dependent density functional theory, we study the optical excitations
      in finite length carbon nanotubes. Evidence of spin-charge separation is given in
      the spacetime domain. We demonstrate that the charge density wave is due to
      collective excitations of electron singlets, while the accompanying spin density
      wave is due to those of electron triplets. The Tomonaga-Luttinger liquid
      parameter and density-density interaction are extrapolated from the first
      principles excitation energies. We show that the density-density interaction
      increases with the length of the nanotube. The singlet and triplet excitation
      energies, on the other hand, decrease for increasing length of the nanotube.
      Their ratio is used to establish a first-principles approach for deriving the
      Tomonaga-Luttinger parameter (in excellent agreement with experimental data).
      Time evolution analysis of the charge and spin line densities evidences that the
      charge and spin density waves are elementary excitations of metallic carbon
      nanotubes. Their dynamics show no dependence on each other.

PMID- 29039675
TI  - Total Synthesis of Paralemnolide A.
AB  - The first total synthesis of tricyclic bisnorsesquiterpene paralemnolide A,
      isolated from the soft coral Paralemnalia thyrsoides, was achieved. This
      synthesis features the lactonization of the cyclohexene derivative having a tert
      butyl ester via stereoselective epoxidation followed by treatment with a Bronsted
      acid and construction of the novel tricyclic skeleton by an intramolecular
      Reformatsky-Honda reaction.

PMID- 29039676
TI  - Mechanism and Stereoselectivity of the BINOL-Catalyzed Allylboration of Skatoles.
AB  - Density functional theory calculations have been performed to investigate the
      binaphthol-catalyzed allylboration of skatoles. The high stereoselectivity
      observed for the reaction is reproduced well by the calculations and was found to
      be mainly a result of steric repulsions in the corresponding Zimmerman-Traxler
      transition states. The role of the additive MeOH in enhancing the
      stereoselectivity was also investigated and is suggested to promote the formation
      of less reactive allylboronic ester intermediates, thereby suppressing the
      formation of allylboroxine species, which undergo the facile racemic background
      reaction.

PMID- 29039677
TI  - Two-Way Transformation between fcc- and Nonfcc-Structured Gold Nanoclusters.
AB  - Precisely tuning the structure of nanomaterials, especially in a two-way style,
      is challenging but of great importance for regulating properties and for
      practical applications. The structural transformation from nonfcc to fcc (face
      center cubic) in gold nanoclusters has been recently reported; however, the
      reverse process, that is, the structural transformation from fcc to nonfcc, not
      to mention the two-way structural transformation between fcc and nonfcc, remains
      unknown. We developed a novel synthesis method, successfully fulfilled the two
      way structure transformation, and studied the stability of gold nanoclusters with
      different structures. Additionally, a novel gold nanocluster was synthesized and
      structurally resolved by single-crystal X-ray crystallography. This work has
      important implications for structure and property tuning of gold nanoclusters and
      might open up some new potential applications for gold nanoclusters.

PMID- 29039678
TI  - Electrochemical Properties of Sulfurized-Polyacrylonitrile Cathode for Lithium
      Sulfur Batteries: Effect of Polyacrylic Acid Binder and Fluoroethylene Carbonate
      Additive.
AB  - Sulfurized carbonized polyacrylonitrile (S-CPAN) is a promising cathode material
      for Li-S batteries owing to the absence of polysulfide dissolution phenomena in
      the electrolyte solutions and thus the lack of a detrimental shuttle mechanism.
      However, challenges remain in achieving high performance at practical loading
      because of large volume expansion of S-CPAN electrodes and lithium anode
      degradation at high current densities. To mitigate this problem, we propose a
      novel cell design including poly(acrylic acid) (PAA) binder for improved
      integrity of the composite electrodes and fluoroethylene carbonate (FEC) as
      additive in the electrolyte solutions for stabilizing the lithium metal surface.
      As a result, these cells delivered high initial discharge capacity of 1500 mAh g
      1 and a superior cycling stability ~98.5% capacity retention after 100 cycles,
      0.5 C rate, and high sulfur loading of 3.0 mg cm-2. Scaled-up 260 mAh pouch cells
      are working very well, highlighting the practical importance of this work.

PMID- 29039679
TI  - Effect of Nanostructured Domains in Self-Assembled Block Copolymer Films on
      Sequential Infiltration Synthesis.
AB  - There are broad interests in selective and localized synthesis in nanodomains of
      self-assembled block copolymers (BCPs) for a variety of applications. Sequential
      infiltration synthesis (SIS) shows promise to selectively grow a controllable
      amount of materials in one type of nanodomain of a self-assembled BCP film.
      However, the effects of nanostructured domains in a BCP film and SIS cycles on
      the material growth behavior of SIS are rarely studied. In this work, we
      investigated the growth behavior of TiO2 SIS within self-assembled polystyrene
      block-poly(methyl methacrylate) (PS-b-PMMA) films and the two corresponding pure
      homopolymer films (PS and PMMA) by using in situ quartz crystal microbalance
      (QCM). According to the experimental results, reactant purge steps are essential
      to enable a high selectivity of SIS in PMMA nanodomains in the BCP films by
      eliminating the undesired homogeneous reactions. The continuous PS nanodomain
      acts as the main channel in transporting reactants to PMMA nanodomains in the
      self-assembled PS-b-PMMA BCP films. The segregated nanoscale PMMA nanodomains in
      the BCP films show dramatically different TiCl4 diffusion/reaction behavior than
      a continuous PMMA film. The mass gain per SIS cycle within PMMA nanodomains
      decreases quickly with increasing cycle number. After 7 TiO2 SIS cycles, TiO2 SIS
      can only take place at the interface between PS and PMMA nanodomains in the BCP
      film. The TiO2 SIS process can uniformly modify PMMA nanodomains throughout a
      self-assembled PS-b-PMMA film up to the diffusion depth owing to the unique
      nanostructure-enabled diffusion. SIS cycle number and chemistry of a BCP will
      strongly affect the material growth behavior of a SIS chemistry on the BCP film
      and, therefore, the final morphology of the resulting nanomaterial. Detailed
      studies are warranted for a SIS process on a self-assembled BCP film of different
      chemistry.

PMID- 29039680
TI  - Solid-Phase Synthesis of beta-Peptoids with Chiral Backbone Substituents Using
      Reductive Amination.
AB  - A new submonomeric synthetic method of beta-peptoids that allows introduction of
      chiral backbone substituents is established. The synthesis of beta-peptoids with
      various backbone substituents on beta-carbons and spectroscopic studies of
      synthesized oligomers are described.

PMID- 29039681
TI  - Complementary and Alternative Medicine Services in the Military Health System.
AB  - OBJECTIVES: Surveys of military personnel indicate substantial use of
      complementary and alternative medicine (CAM) that possibly exceeds use in the
      general U.S. POPULATION: Although military treatment facilities (MTFs) are known
      to offer CAM, surveys do not indicate where service members receive this care.
      This study offers a comprehensive system-wide accounting of the types of CAM
      offered across the military health system (MHS), the conditions for which it is
      used, and its level of use. These data will help MHS policymakers better support
      their population's healthcare needs. DESIGN: A census survey of MTFs across the
      MHS on all CAM use, supplemented where possible by MHS utilization data. OUTCOME
      MEASURES: Types of CAM offered by each MTF, reasons given for offering CAM,
      health conditions for which CAM is used, and number of patient visits for each
      CAM type. RESULTS: Of the 142 MTFs in the MHS, 133 (94%) responded. Of these, 110
      (83%) offer at least one type of CAM and 5 more plan to offer CAM services in the
      future. Larger MTFs (those reporting >=25,000 beneficiaries enrolled) are both
      more likely to offer CAM services (p < 0.001) and a larger number (>10) of
      different types of CAM (p = 0.010) than smaller MTFs. Three-fourths of MTFs
      offering CAM provide stress management/relaxation therapy, two-thirds provide
      acupuncture, and at least half provide progressive muscle relaxation, guided
      imagery, chiropractic, and mindfulness meditation. MTFs most commonly report CAM
      use for pain and mental health conditions. Acupuncture and chiropractic are most
      commonly used for pain, and stress management/relaxation therapy and mind-body
      medicine combinations are most often used for mental health-related conditions.
      We estimate 76,000 CAM patient encounters per month across the MHS. CONCLUSIONS:
      The availability of CAM services in the MHS is widespread and is being used to
      address a range of challenging pain and mental health conditions.

PMID- 29039682
TI  - On the Habitability of Desert Varnish: A Combined Study by Micro-Raman
      Spectroscopy, X-ray Diffraction, and Methylated Pyrolysis-Gas Chromatography-Mass
      Spectrometry.
AB  - In 2020, the ESA ExoMars and NASA Mars 2020 missions will be launched to Mars to
      search for evidence of past and present life. In preparation for these missions,
      terrestrial analog samples of rock formations on Mars are studied in detail in
      order to optimize the scientific information that the analytical instrumentation
      will return. Desert varnishes are thin mineral coatings found on rocks in arid
      and semi-arid environments on Earth that are recognized as analog samples. During
      the formation of desert varnishes (which takes many hundreds of years), organic
      matter is incorporated, and microorganisms may also play an active role in the
      formation process. During this study, four complementary analytical techniques
      proposed for Mars missions (X-ray diffraction [XRD], Raman spectroscopy,
      elemental analysis, and pyrolysis-gas chromatography-mass spectrometry [Py-GC
      MS]) were used to interrogate samples of desert varnish and describe their
      capacity to sustain life under extreme scenarios. For the first time, both the
      geochemistry and the organic compounds associated with desert varnish are
      described with the use of identical sets of samples. XRD and Raman spectroscopy
      measurements were used to nondestructively interrogate the mineralogy of the
      samples. In addition, the use of Raman spectroscopy instruments enabled the
      detection of beta-carotene, a highly Raman-active biomarker. The content and the
      nature of the organic material in the samples were further investigated with
      elemental analysis and methylated Py-GC-MS, and a bacterial origin was determined
      to be likely. In the context of planetary exploration, we describe the habitable
      nature of desert varnish based on the biogeochemical composition of the samples.
      Possible interference of the geological substrate on the detectability of
      pyrolysis products is also suggested. Key Words: Desert varnish-Habitability
      Raman spectroscopy-Py-GC-MS-XRD-ExoMars-Planetary science. Astrobiology 17, 1123
      1137.

PMID- 29039683
TI  - A systematic review of Federal Drug Administration Docket for community
      consultation and public disclosure in exception from informed consent trials.
AB  - BACKGROUND: Exception from informed consent imposes community consultation and
      public disclosure requirements on clinical investigation in critically ill and
      injured patients. In 2011, the Food and Drug Administration instructed sponsors
      to submit publically disclosed information to the Food and Drug Administration
      Docket, but to date there has been no comprehensive analysis of available data.
      We summarized the community consultation and public disclosure practices of
      exception from informed consent trials published on the Food and Drug
      Administration Docket in order to better understand the breadth of common
      practices that exists among acute care clinical research. METHODS: We performed
      quantitative and qualitative analysis of Docket FDA-1995-S-0036 from its
      initiation until June 2017 in order to summarize existing practices. We developed
      a 4-point scoring system to categorize public disclosure and community
      consultation based on inclusion of key components such as a detailed plan,
      schedule of events conducted, results, and materials uploaded. RESULTS: The 177
      docket submissions represented 34 trials. Material related to public disclosure
      accounted for 49% of pages, community consultation 45%, and 6% other. The median
      Docket Review Content Score for public disclosure was 3 (mean: 2.5, range: 0-4)
      and 2 (mean: 2.1, range: 0-4) for community consultation materials. CONCLUSION:
      The public information contained in the Docket varies broadly by trial and
      content. Additionally, as evidenced by the wide range of the Docket Review
      Content Score, submission guidelines are not followed uniformly. Given the
      apparent uncertainty about what should be submitted, and the need for best
      practice recommendations, it is valuable to categorize and summarize existing
      community consultation and public disclosure content.

PMID- 29039684
TI  - Parenting Stress in Parents of Infants With Congenital Heart Disease and Parents
      of Healthy Infants: The First Year of Life.
AB  - While we know that the parents of infants with congenital heart disease (CHD),
      the most prevalent group of congenital anomalies, experience increased parenting
      stress, the stress levels throughout infancy have yet to be studied. Stress
      experienced by parents beyond the normative stress of parenting can interfere
      with parenting processes, and bear adverse family outcomes. This prospective
      cohort study was conducted to describe and compare parenting stress levels during
      infancy between parents of infants with complex CHD and parents of healthy
      infants. The Parenting Stress Index-Long Form was distributed to parents of
      infants with complex CHD and parents of healthy infants (N = 129). T-tests were
      used to compare stress between groups at 3, 6, 9, and 12 months of age. Parents
      of infants with complex CHD had higher parenting stress than parents of healthy
      infants on multiple subscales on the Child and Parent Domains, at 3 months of
      age. The stress remained higher on the demandingness subscale throughout infancy.
      Parents of CHD infants also demonstrated significantly higher stress scores on
      the life stress subscale at 12 months of age. Findings highlight stressful
      periods related to parenting infants with CHD, which may increase existing psycho
      social risk for parents of infants with CHD. Early family intervention may
      promote parental adaptation to the illness, and help establishing healthy
      parenting practices.

PMID- 29039685
TI  - Health technology assessment process of a cardiovascular medical device in four
      different settings.
AB  - AIM: Health technology assessment (HTA) is a tool to help the decision-making
      process. The aim is to describe methods and processes used in the reimbursement
      decision making for drug-eluting stents (DES) in four different settings.
      METHODS: DES as a technology under study was selected according to different
      criteria, all of them agreed by a working group. A survey of key informants was
      designed. RESULTS: DES was evaluated following well-structured HTA processes.
      Nonetheless, scope for improvement was observed in relation to the data
      considered for the final decision, the transparency and inclusiveness of the
      process as well as in the methods employed. CONCLUSION: An attempt to describe
      the HTA processes of a well-known medical device.

PMID- 29039686
TI  - Prevention and treatment of HIV infection in neonates: evidence base for existing
      WHO dosing recommendations and implementation considerations.
AB  - INTRODUCTION: Antiretroviral drugs are used in neonates for prevention and
      treatment of HIV infection. Use of antiretrovirals to prevent perinatal HIV
      transmission is well established. Early identification of neonates infected with
      HIV and rapid initiation of combination antiretroviral treatment during the
      neonatal period is now recommended by WHO and DHHS. However, few antiretrovirals
      are available in formulations suitable for neonates and there are limited safety
      and pharmacokinetic data for most antiretrovirals in neonates. Areas covered: We
      summarize existing neonatal antiretroviral safety and pharmacokinetic information
      and discuss implementation considerations for programs providing antiretrovirals
      to neonates and young infants. Expert commentary: Antiretrovirals currently
      recommended by WHO for use in neonates are zidovudine, lamivudine,
      lopinavir/ritonavir, nevirapine, and raltegravir. Significant implementation
      challenges exist to the widespread use of these antiretrovirals in neonates.
      Optimal, feasible treatment of HIV-exposed and HIV-infected newborns will require
      development of practical neonatal dosage forms and their study in neonates for a
      wide range of antiretrovirals.

PMID- 29039687
TI  - "Context Matters:" An Exploration of Young Adult Social Constructions of Meaning
      About Death and Dying.

PMID- 29039688
TI  - MELC Genomics: A Framework for De Novo Genome Assembly.
AB  - The development of next-generation sequencing platforms increased substantially
      the capacity of data generation. In addition, in the past years, the costs for
      whole genome sequencing have been reduced that made it easier to access this
      technology. As a result, the storage and analysis of the data generated became a
      challenge, ushering in the development of bioinformatic tools, such as programs
      and programming languages, able to store, process, and analyze this huge amount
      of information. In this article, we present MELC genomics, a framework for genome
      assembly in a simple and fast workflow.

PMID- 29039689
TI  - Anti-Stigma HIV-Related Social Advertising: No Evidence for Side Effects on
      Condom Use.
AB  - Recent campaigns try to reduce social stigma associated with persons living with
      HIV. For example, a German campaign raised awareness that infection is unlikely
      in low-risk day-to-day interactions. Research has yet to show that there are no
      harmful side effects. This is essential because such messages promote a less
      threatening picture of HIV and thus may unintentionally increase complacency. We
      tested the possible side effects on the willingness to have sex without condoms.
      An experiment was conducted in which participants were exposed to anti-stigma
      messages or not. Anti-stigma messages did not elicit an increase in the
      willingness to have sex without condoms.

PMID- 29039690
TI  - Unilateral pulmonary artery pre-operative occlusion test: technical feasibility
      and safety prior to pneumonectomy or pleuropneumonectomy for malignancy.
AB  - OBJECTIVE: The aim of the present study was to assess the technical feasibility
      and safety of the unilateral pulmonary artery occlusion (UPAO) test in pre
      operative evaluation of pneumonectomy or pleuropneumonectomy for lung or pleural
      tumours. METHODS: The UPAO test was performed on 91 patients who were scheduled
      to undergo or were being considered for pneumonectomy or pleuropneumonectomy
      between June 2003 and July 2016. There were 74 males and 17 females, with a
      median age of 65 years (range, 23-80). The technical success rate, procedure time
      and complication rate were evaluated. Technical success was defined as completion
      of the UPAO test. RESULTS: The diagnoses of the 91 patients were as follows: lung
      cancer in 63, malignant pleural mesothelioma in 21, thymoma in 5, lung metastasis
      in 1 and lung carcinoid in 1. The UPAO test was performed successfully on 88 out
      of 91 patients (technical success rate: 97%). The median procedure time was 57
      min (range, 34-120). Cardiac arrest due to migration of the balloon catheter to
      the pulmonary trunk occurred in 1 patient (complication rate: 1.1%). CONCLUSION:
      The UPAO test in pre-operative evaluation of pneumonectomy or pleuropneumonectomy
      for lung or pleural tumours appears to be technically feasible. However, it needs
      to be performed with care in order to avoid severe complications. Advances in
      knowledge: The UPAO test can be safely performed and is helpful in evaluating
      patients for pneumonectomy or pleuropneumonectomy.

PMID- 29039691
TI  - Inefficiency, dignity and patient experience: is it time for separate outpatient
      diagnostics?
AB  - There is international and national variation in the location of diagnostic
      imaging centres relative to hospitals. Diagnostic cross-sectional imaging has
      traditionally been performed within a hospital, catering for both inpatient and
      outpatients. The resulting two-tiered system caters for emergent and complex
      inpatients, in addition to typically ambulatory outpatients. These outpatients
      are less complex, and often attend an acute hospital for the specific purpose of
      diagnostic imaging. In both the UK and the Republic of Ireland, outpatient
      radiology is often provided on-campus in state-funded hospitals, reflecting the
      allocation of resources nationally. In many other countries, hospitals provide
      acute and high-level care, with community centres addressing outpatients'
      clinical and diagnostic needs. Mixing inpatients and outpatients introduces
      variability into the scanning process, and many institutions struggle to provide
      for the very different needs of outpatients. Current strategies of mixing these
      two fundamentally different groups should be reassessed, and either in-hospital
      segregation or dedicated outpatient diagnostic imaging centres merit serious
      consideration in any future healthcare planning.

PMID- 29039693
TI  - Variation in adherence to medications across the healthcare system in two
      comparative effectiveness research cohorts.
AB  - AIM: To assess heterogeneity in adherence to medications in two example
      comparative effectiveness research studies. PATIENTS & METHODS: We analyzed data
      from commercially insured patients initiating a statin or anticoagulant during
      2005-2012. We calculated the cross-validated R2 from a series of hierarchical
      linear models to assess variation in 1-year adherence. RESULTS: There was less
      heterogeneity in adherence in the statin cohort compared with the anticoagulant
      cohort, where patient characteristics explained 7.2% of variation in adherence,
      and adding therapy and provider characteristics increased the proportion of
      variation explained to 8.0 and 8.5%, cumulatively. Random effects provided
      essentially no explanatory power, even in the statin cohort with large numbers of
      patients clustered within each pharmacy, prescriber and provider. CONCLUSION: The
      dependence of adherence on the healthcare system was stronger when the healthcare
      system influenced treatment choice and patient access to medication and when
      indications for treatment were strong.

PMID- 29039694
TI  - Can a Pink Ribbon Actually Limit Awareness?

PMID- 29039692
TI  - Imaging spectrum of immunomodulating, chemotherapeutic and radiation therapy
      related intracranial effects.
AB  - OBJECTIVE: A wide range of treatment-related side effects result in specific
      neurologic symptoms and signs and neuroimaging features. Even to the most
      seasoned neuroradiologist, elucidating therapy-related side effects from other
      common mimics can be challenging. We provide a pictorial survey of some common
      and uncommon medication-induced and therapy-related neuroimaging manifestations,
      discuss pathophysiology and common pitfalls in imaging and diagnosis. METHODS: A
      case-based review is utilized to depict scenarios on a routine basis in a general
      radiology or neuroradiology practice such as medication-induced posterior
      reversible encephalopathy syndrome to the more challenging cases of
      pseudoprogression and pseudoregression in temozolmide and bevacizumab therapy in
      gliobastoma treatment protocols. CONCLUSION: Knowledge of the treatment-induced
      imaging abnormalities is essential in the accurate interpretation and diagnosis
      from the most routine to most challenging of clinical situations. We provide a
      pictorial review for the radiologist to employ in order to be an invaluable
      provider to our clinical colleagues and patients.

PMID- 29039695
TI  - Board Walk - October 2017.

PMID- 29039698
TI  - An Experimental Test of How Selfies Change Social Judgments on Facebook.
AB  - Selfies are everywhere on social media. Research has focused only on who is
      posting selfies and has not addressed the audience members viewing selfies. This
      study aims to fill this gap by analyzing the judgments people make of selfies
      posted on Facebook. Using an online experiment, we test how including a selfie on
      a Facebook status update changes people's appraisals of narcissism, message
      appropriateness, and social attraction. We also consider how the valence and
      intimacy of the status update text interplay with the selfie to change social
      judgments. Participants rated posts with selfies as more narcissistic and
      inappropriate, and less socially attractive. Selfie evaluations also depended
      upon the valence and intimacy of the status update text. Gender of the selfie
      poster did not influence evaluation of posts. One implication from these results
      is that posting selfies on social media may lead to negative judgments about the
      poster.

PMID- 29039697
TI  - An Investigation of the Information Sought by Caregivers of Alzheimer's Patients
      on Online Peer Support Groups.
AB  - Caregivers of Alzheimer's patients find respite in online communities for
      solutions and emotional support. This study aims to understand the
      characteristics of information caregivers of Alzheimer's patients are searching
      for and the kind of support they receive through Internet-based peer support
      communities. Using a Web crawler written in Python Web programming language, we
      retrieved publicly available 2,500 random posts and their respective solutions
      from April 2012 to October 2016 on the solutions category of the Caregiver's
      Forum on ALZConnected.org . A content analysis was conducted on these randomly
      selected posts and 4,219 responses to those posts based on a classification
      system were derived from initial analyses of 750 posts and related responses. The
      results showed most posts (26%) related to queries about Alzheimer's symptoms,
      and the highest percentage of responses (45.56%) pertained to caregiver well
      being. The LIWC analyses generated an average tone rating of 27.27 for the posts,
      implying a negative tone and 65.17 for their responses, implying a slightly
      positive tone. The ALZConnected.org Web site has the potential of being an
      emotionally supportive tool for caregivers; however, a more user-friendly
      interface is required to accommodate the needs of most caregivers and their
      technological skills. Solutions offered on the peer support groups are often
      subjective opinions of other caregivers and should not be considered professional
      or comprehensive; further research on educating caregivers using online forums is
      necessary.

PMID- 29039699
TI  - Personality Traits, Motivations, and Emotional Consequences of Social Media
      Usage.
AB  - This study explores social media users' personality traits and motivations for
      the usage of two different social media platforms, Facebook and Pinterest, as
      well as how the varied uses impact users' negative emotional experiences. The
      findings suggest that the intensity of social media usage is positively related
      to negative emotions. For Facebook users, socialization, entertainment, and
      information seeking motivations significantly influence their platform use
      intensity and, subsequently, lead to negative emotions. Self-status seeking also
      has a direct effect on Facebook users' negative emotions. For Pinterest users,
      socialization is not a significant motivation for usage of that platform.
      However, entertainment, information seeking, and self-status seeking
      significantly predict their platform use intensity, which subsequently lead to
      negative emotions. Similarly, all four motivations for Facebook and Pinterest
      uses are influenced by users' personality traits: extraversion and openness. Yet,
      openness has a greater impact on using Pinterest than Facebook in terms of
      fulfilling socialization needs. Neuroticism has a positive impact on
      socialization and information seeking motives for use of both platforms, while
      conscientiousness and agreeableness have a negative influence on fulfilling self
      status seeking needs. In addition, agreeable social networking site users are
      less likely to use Facebook than Pinterest for fulfilling self-status related
      gratifications, while they are likely to use Pinterest instead of Facebook for
      entertainment and information needs. Implications of the findings and suggestions
      for future research are discussed.

PMID- 29039701
TI  - Collective Grieving in the Digital Age.

PMID- 29039700
TI  - Browsing, Posting, and Liking on Instagram: The Reciprocal Relationships Between
      Different Types of Instagram Use and Adolescents' Depressed Mood.
AB  - Although studies have shown that Instagram use and young adults' mental health
      are cross-sectionally associated, longitudinal evidence is lacking. In addition,
      no study thus far examined this association, or the reverse, among adolescents.
      To address these gaps, we set up a longitudinal panel study among 12- to 19-year
      old Flemish adolescents to investigate the reciprocal relationships between
      different types of Instagram use and depressed mood. Self-report data from 671
      adolescent Instagram users (61% girls; MAge = 14.96; SD = 1.29) were used to
      examine our research question and test our hypotheses. Structural equation
      modeling showed that Instagram browsing at Time 1 was related to increases in
      adolescents' depressed mood at Time 2. In addition, adolescents' depressed mood
      at Time 1 was related to increases in Instagram posting at Time 2. These
      relationships were similar among boys and girls. Potential explanations for the
      study findings and suggestions for future research are discussed.

PMID- 29039703
TI  - The Relationship Between Resilience and Internet Addiction: A Multiple Mediation
      Model Through Peer Relationship and Depression.
AB  - Heavy use of the Internet may lead to profound academic problems in elementary
      students, such as poor grades, academic probation, and even expulsion from
      school. It is of great concern that Internet addiction problems in elementary
      school students have increased sharply in recent years. In this study, 58,756
      elementary school students from the Henan province of China completed four
      questionnaires to explore the mechanisms of Internet addiction. The results
      showed that resilience was negatively correlated with Internet addiction. There
      were three mediational paths in the model: (a) the mediational path through peer
      relationship with an effect size of 50.0 percent, (b) the mediational path
      through depression with an effect size of 15.6 percent, (c) the mediational path
      through peer relationship and depression with an effect size of 13.7 percent. The
      total mediational effect size was 79.27 percent. The effect size through peer
      relationship was the strongest among the three mediation paths. The current
      findings suggest that resilience is a predictor of Internet addiction. Improving
      children's resilience (such as toughness, emotional control, and problem solving)
      can be an effective way to reduce Internet addiction behavior. The current
      findings provide useful information for early detection and intervention for
      Internet addiction.

PMID- 29039704
TI  - Beat the Fear of Public Speaking: Mobile 360 degrees  Video Virtual Reality
      Exposure Training in Home Environment Reduces Public Speaking Anxiety.
AB  - With this article, we aim to increase our understanding of how mobile virtual
      reality exposure therapy (VRET) can help reduce speaking anxiety. Using the
      results of a longitudinal study, we examined the effect of a new VRET strategy
      (Public Speech Trainer, PST), that incorporates 360 degrees  live recorded VR
      environments, on the reduction of public speaking anxiety. The PST was developed
      as a 360 degrees  smartphone application for a VR head-mounted device that
      participants could use at home. Realistic anxiety experiences were created by
      means of live 360 degrees  video recordings of a lecture hall containing three
      training sessions based on graded exposure framework; empty classroom (a) and
      with a small (b) and large audience (c). Thirty-five students participated in all
      sessions using PST. Anxiety levels were measured before and after each session
      over a period of 4 weeks. As expected, speaking anxiety significantly decreased
      after the completion of all PST sessions, and the decrement was the strongest in
      participants with initially high speaking anxiety baseline levels. Results also
      revealed that participants with moderate and high speaking anxiety baseline level
      differ in the anxiety state pattern over time. Conclusively and in line with
      habituation theory, the results supported the notion that VRET is more effective
      when aimed at reducing high-state anxiety levels. Further implications for future
      research and improvement of current VRET strategies are discussed.

PMID- 29039705
TI  - Research on Web Search Behavior: How Online Query Data Inform Social Psychology.
AB  - The widespread use of web searches in daily life has allowed researchers to study
      people's online social and psychological behavior. Using web search data has
      advantages in terms of data objectivity, ecological validity, temporal
      resolution, and unique application value. This review integrates existing studies
      on web search data that have explored topics including sexual behavior, suicidal
      behavior, mental health, social prejudice, social inequality, public responses to
      policies, and other psychosocial issues. These studies are categorized as
      descriptive, correlational, inferential, predictive, and policy evaluation
      research. The integration of theory-based hypothesis testing in future web search
      research will result in even stronger contributions to social psychology.

PMID- 29039706
TI  - Associations of Self-Presentation on Facebook with Mental Health and Personality
      Variables: A Systematic Review.
AB  - Many investigations of the associations of self-presentation on Facebook with
      mental health and personality variables exist, but their findings have not yet
      been synthetized. We therefore carried out a narrative synthesis of 21
      observational studies (combined N = 7,573) obtained from a systematic search of
      four academic databases. Significant self-presentation associations were yielded
      for self-esteem, perceived social support, social anxiety, well-being,
      depression, bipolar/mania, stress, self-consciousness, and insecure attachment.
      Significant associations were also yielded for all of the big five personality
      variables and narcissism. The clearest trends-based on the number of times
      significant associations were yielded across included studies-were as follows:
      (1) inauthentic self-presentation was consistently associated with low self
      esteem and elevated levels of social anxiety; (2) inauthentic self-presentation
      was consistently more likely to occur in people high in neuroticism and
      narcissism; and (3) authentic/positive self-presentation was consistently
      associated with increased levels of self-esteem and perceived social support. The
      assessment of online self-presentation may offer clinicians important insights
      into how clients are functioning in relation to various domains of mental health
      and personality. For example, clients who present inauthentic versions of
      themselves on Facebook could be experiencing social anxiety or have maladaptive
      personality traits such as neuroticism and narcissism, all of which could be
      targeted in intervention.

PMID- 29039707
TI  - First Detection of CTX-M-1 in Extended-Spectrum beta-Lactamase-Producing
      Escherichia coli in Seafood from Tunisia.
AB  - The purpose of this study was to determine the carriage rate of Escherichia coli
      isolates in seafood, to analyze the phenotype and genotype of antimicrobial
      resistance in the recovered isolates, and to characterize extended-spectrum beta
      lactamase (ESBL) E. coli producers. E. coli isolates were recovered from 24
      (34.3%) of the 70 seafood samples analyzed, and one isolate per sample was
      further characterized. Antibiotic resistance was determined by the disk diffusion
      method in the 24 isolates, with the following results (number of resistant
      isolates): tetracycline (8), streptomycin (7), ampicillin (6), trimethoprim
      sulfamethoxazole (4), chloramphenicol (4), ciprofloxacin (3), cefotaxime (2), and
      ceftazidime (2). Six isolates showed a multiresistant phenotype (including at
      least three families of antibiotics). Among tetracycline-resistant E. coli
      isolates, tet(A) was detected in five isolates and tet(B) in two isolates. The
      qnr(A) or aac(6')-1b-cr genes were detected in two ciprofloxacin-resistant E.
      coli isolates, and the sul2 gene in two trimethoprim-sulfamethoxazole-resistant
      isolates. ESBL-containing E. coli isolates, carrying the blaCTX-M-1 gene, were
      detected in 2 of the 70 seafood samples, obtained from gilt-head bream
      aquaculture. The ESBL isolates were typed phylogenetically and by multilocus
      sequence typing, and they were ascribed to lineage ST48/A and to the new
      ST3497/B1; these isolates carried the fimA, aer, and papGIII virulence genes. One
      of the ESBL-producing E. coli isolates carried an unusual class 1 integron (with
      the array dfr32-ereA-aadA1). Seafood could be a source of multiresistant E. coli
      isolates for the aquatic environment, and these could enter the food chain.

PMID- 29039708
TI  - Detection of Total and Pathogenic Vibrio parahaemolyticus in Shellfish Growing
      along the South Yellow Sea and the East China Sea.
AB  - This study was conducted to monitor the densities of total and pathogenic Vibrio
      parahaemolyticus in 300 samples of nine shellfish species harvested from the
      coasts of the South Yellow Sea and the East China Sea (N 23 degrees  to 34
      degrees , E 116 degrees  to 124 degrees ), People's Republic of China, between
      May and October 2015. Total V. parahaemolyticus densities were measured, and V.
      parahaemolyticus isolates were biochemically identified with probes for the
      thermostable direct hemolysin gene (tdh) and the thermostable direct hemolysin
      related hemolysin gene (trh). We found that 202 of the 300 samples were positive
      for V. parahaemolyticus from all the sites: 58 of the 100 samples from the Fujian
      province, 71 of the 100 samples from the Zhejiang province, and 73 of the 100
      samples from the Jiangsu province. In most (170) of the 300 samples, V.
      parahaemolyticus densities were 0.3 to 10 most probable number (MPN)/g; five lots
      exceeded 110 MPN/g, and two lots were estimated at 110 MPN/g. Among the 202 V.
      parahaemolyticus strains, only one was trh positive. Densities of V.
      parahaemolyticus in these shellfish were temperature dependent, with highest
      densities in June and July. Among the nine mollusk species, V. parahaemolyticus
      was most abundant in the agemaki clam (Sinonovacula constricta). The highest and
      lowest V. parahaemolyticus prevalences were found in oriental cyclina (Cyclina
      sinensis, 93.8%) and mussels (Mytilus edulis, 28.1%), respectively. Overall,
      although V. parahaemolyticus is widely distributed in marine environments, the
      density of V. parahaemolyticus was low and the prevalence of the main virulence
      factor was very low in shellfish along the coasts of the South Yellow Sea and
      East China Sea, which is important from a public health perspective. Data
      presented here will be useful for correlational research and can be utilized for
      developing risk management plans that establish food safety guidelines for V.
      parahaemolyticus in Chinese shellfish.

PMID- 29039709
TI  - Survey of Veterinary Drug Residues in Raw Milk in Hebei Province, China.
AB  - The objective of this study was to investigate the occurrence of veterinary drug
      residues in raw milk from Hebei, the second-largest dairy production province in
      the People's Republic of China. A total of 192 raw milk samples were collected
      from 64 milk stations in seven districts. Twenty-eight veterinary drug residues
      were analyzed by ultraperformance liquid chromatography with tandem mass
      spectrometry based on a China National Standard. Raw milk samples with multiple
      residues of veterinary drugs were not found in the present study. Residues of
      four veterinary drugs, penicillin G, sulfacetamide, trimethoprim, and lincomycin,
      were detected in 12 (6.25%) raw milk samples, with detection ratios of 1.04,
      0.52, 3.13, and 1.56%, respectively. All veterinary drug residues detected were
      under the maximum residue levels as regulated by China, the European Union, the
      United States, and the Codex Alimentarius Commission. In general, raw milk from
      Hebei province was considered relatively safe for human consumption because of
      the low prevalence of veterinary drug residues. However, stringent control
      measurements for veterinary drug residues in raw milk are required because some
      veterinary drugs were detected in milk from some areas of Hebei province.

PMID- 29039710
TI  - One-Year Mixed-Methods Case Study of a Community-Academic Advisory Board
      Addressing Childhood Obesity.
AB  - OBJECTIVE: Using a community-based participatory research and systems-based
      approach, the purpose of this community case study is to describe the planning
      process and first-year experiences of community-academic advisory board (CAB)
      partners involved with the development of an evidence-based childhood obesity
      treatment program in a medically underserved region. METHOD: Regional community
      partners ( n = 9; Pittsylvania/Danville Health District, Children's Healthcare
      Center, Danville Parks & Recreation, and Danville Boys & Girls Club) and academic
      partners ( n = 9) met monthly to select and adapt an evidence-based childhood
      obesity program, develop evaluation and recruitment protocols, and plan for
      program implementation. In the first 3 months, members developed a mixed-methods
      capacity evaluation, administered at 3 and 11 months following the first CAB
      meeting. RESULTS: Most capacity dimensions were rated highly and demonstrated no
      significant change over time. However, perceptions of trust approached a
      significant increase ( p = .055), the ability to resolve conflicts significantly
      increased ( p = .018), and participation and influ-ence perceptions significantly
      decreased ( p = .001). Qualitative analysis elucidated members' experiences and
      key facilitator and barrier themes emerged. CONCLUSIONS: Similarities and
      differences between community and academic members' experiences allowed synthesis
      of best practices and lessons learned. The methodological framework and best
      practices can inform the capacity development for new community-academic
      collaborations.

PMID- 29039712
TI  - The management of refractory carcinoid syndrome: challenges and opportunities
      ahead.

PMID- 29039711
TI  - Farewell.

PMID- 29039713
TI  - Eleanor Clarke Slagle: Facts and Myths.
AB  - Although the name, Eleanor Clarke Slagle, is well known to occupational therapy
      practitioners, her personal history is less known and published accounts vary in
      the degree of accuracy. This article is based on a historical research technique
      known as source criticism that focuses on using accounts published during the
      individual's lifetime that can be verified, when possible, through more than one
      source. The purpose is to present an accurate history of Mrs. Slagle as a person
      who influenced the history and development of occupational therapy practice in
      the United States.

PMID- 29039714
TI  - Causal Factors of Increased Smoking in ADHD: A Systematic Review.
AB  - BACKGROUND: ADHD is a highly prevalent disorder and poses a risk for a variety of
      mental disorders and functional impairments into adulthood. One of the most
      striking comorbidities of ADHD is nicotine dependence. Youth diagnosed with ADHD
      are 2-3 times more likely to smoke than their peers without ADHD, initiate
      smoking earlier in life and progress more quickly and more frequently to regular
      use and dependence. Possible explanations for these increased risks are: (a) self
      medication of ADHD symptoms with the stimulant nicotine; (b) ADHD symptoms like
      inattention and hyperactivity/impulsivity predispose for smoking initiation and
      impede smoking cessation; (c) peer pressure; and/or (d) common genetic or
      environmental determinants for ADHD and smoking. OBJECTIVE: Identify the most
      probable causes of the high prevalence of smoking and nicotine dependence in
      subjects with ADHD. METHODS: A systematic literature review was performed and the
      causality of the observed relations was ranked using the Bradford Hill criteria.
      FINDINGS: ADHD medication reduces early smoking initiation and alleviates smoking
      withdrawal. Nicotine patches, bupropion and (probably) varenicline ameliorate
      ADHD symptoms. Imitation of and interaction with peers and genetic and
      environmental determinants may contribute to the comorbidity, but seem to
      contribute less than self-medication. CONCLUSION: Smoking is probably best
      explained by a combination of imitation, peer pressure and typical traits of
      ADHD. In contrast, the positive relation between ADHD and nicotine dependence is
      currently best explained by the self-medication hypothesis. This hypothesis has a
      clear pharmacological rationale and is supported by ample evidence, but awaits
      confirmation from longitudinal naturalistic studies.

PMID- 29039715
TI  - Antibiotic Resistance in Salmonella from Retail Foods of Animal Origin and Its
      Association with Disinfectant and Heavy Metal Resistance.
AB  - This study aims to demonstrate the antibiotic resistance and its association with
      disinfectant and heavy metal resistance in 152 Salmonella isolates recovered from
      retail foods of animal origins. Susceptibility testing demonstrated that 92.8%
      isolates were resistant to at least one antibiotic, and the resistance was
      highest to oxytetracycline (80.9%), followed by trimethoprim (64.5%), amoxicillin
      (28.9%), ampicillin (28.3%), levofloxacin (21.7%), ciprofloxacin (16.4%), and
      gentamicin (10.5%), respectively. The blaTEM and tetA genes (44.7%) were commonly
      present. The qacF and qacEDelta1 genes were detected in 18.4% and 8.6% of all
      isolates. The Cu-resistance genes pcoR, pcoC, and pcoA were the most prevalent
      (20.4-40.8%), followed by Hg-resistance gene merA (17.8%) and As-resistance genes
      arsB (6.6%). The antibiotic resistance was highly associated with disinfectant or
      certain heavy metal resistance genes. Most notably, the association among Cu
      resistance genes (pcoC, pcoR), disinfectant resistance genes (qacF, qacEDelta1),
      and tetracycline and sulfonamide resistance genes (tet, sul) was significant (p <
      0.05). Pulsed-field gel electrophoresis revealed that Salmonella isolates was
      associated with supermarkets indicating the possibility of crosscontamination in
      farms or processing environment. This study indicated that retail meats may be a
      reservoir for the dissemination of antibiotic-resistant Salmonella and using
      disinfectants for decontamination or metals in livestock may provide a pressure
      for coselecting strains with acquired resistance to other antimicrobials.

PMID- 29039716
TI  - Psychometric Properties of the Iranian-Children Participation Questionnaire (I
      CPQ) When Used with Parents of Preschool Children with Cerebral Palsy.
AB  - The purpose of the study was to establish the psychometric properties of the
      Iranian-Children Participation Questionnaire (I-CPQ) among parents (n = 120) of
      preschool children with cerebral palsy. The mean age of the preschool children
      was 5.1 years old. The confirmatory factor analysis was conducted in two stages,
      and the values of all goodness of fit tests reached an acceptable level (greater
      than 0.9), and achieved an acceptable root mean square error of approximation
      model fit value of 0.05. The results of convergent validity with the Vineland
      Adaptive Behavior Scale for all subtests were significant. Internal consistency
      was acceptable to excellent (alpha: 0.66-0.85), and test-retest reliability was
      excellent (ICC: 0.92-0.98). We concluded that the I-CPQ demonstrated good
      psychometric properties and utility for assessing participation of Iranian
      preschool children with cerebral palsy.

PMID- 29039717
TI  - High Prevalence of Multidrug-Resistant Bacteria in Libyan War Casualties Admitted
      to a Tertiary Care Hospital, Germany.
AB  - The ongoing Libyan conflict constantly causes victims among the military and
      civilian population. Cross-border transfer of patients represents a high risk of
      introducing multidrug-resistant organisms (MDROs), for example, methicillin
      resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, and
      carbapenem-resistant gram-negative organisms (CROs), into the country of
      destination. This study assessed the MDRO status in Libyan war casualties (n =
      67) admitted to Northwest Medical Centre in Frankfurt/Main, Germany, from August
      2016 till January 2017. Identified multidrug-resistant nonfermenters and
      Enterobacteriaceae were subjected to molecular detection of beta-lactamases and
      further mechanisms of resistance. All isolates were typed by enzymatic
      macrorestriction and subsequent pulsed-field gel electrophoresis. MDROs were
      found in 40 (60%) patients, including 25 (37%) positive for at least one CRO and
      11 (16%) patients with MRSA. A total of 37 isolates of Klebsiella pneumoniae,
      Acinetobacter baumannii, Escherichia coli, Enterobacter cloacae, and Serratia
      marcescens produced carbapenemases: NDM (n = 17), OXA-48 (n = 15), and OXA-23 (n
      = 9) in addition to other beta-lactamases (with blaCTX-M-group-1 being most
      frequent) and plasmid-mediated quinolone resistance genes (qnrB, aac(6')Ib-cr).
      Bacterial strain typing revealed the presence of various clones. This high MDRO
      rate in Libyan war casualties demands awareness, appropriate screening, and
      containment measures for medical institutions involved in medical care to avoid
      patient-to-patient transmission.

PMID- 29039718
TI  - Current status of proteomics of soft tissue sarcomas.
AB  - INTRODUCTION: Proteomics has been used in soft tissue sarcoma (STS) research in
      the attempts to improve the understanding of the disease background and develop
      novel clinical applications. Using various proteomics modalities, aberrant
      regulations of numerous intriguing proteins were identified in STSs, and the
      possible utilities of identified proteins as biomarkers or therapeutic targets
      have been explored. STS is an exceptionally diverse group of malignant diseases
      with highly complex molecular backgrounds and, therefore, an overview of the
      achievements and prospects of STS proteomics could enhance our knowledge of the
      possibilities and limitations of cancer proteomics. Areas covered: This review
      examines all STSs that have been examined using proteomics modalities, discussing
      unique aspects, limitations, and possible improvements of individual reports. To
      contribute to the current progress in cancer treatment development using novel
      anti-cancer drugs, proteomics plays a central role in linking cutting-edge
      technologies, application of proteogenomics, patient-derived cancer models, and
      biobanking system. Expert commentary: Therefore, proteomic-based STS research
      will be developed as an interdisciplinary science. STS proteomics will be further
      developed based on the interaction of oncologists with basic researchers in
      various fields, aimed at obtaining an enhanced understanding of the biology of
      the disease and achieving superior clinical outcomes for patients.

PMID- 29039720
TI  - Trends in the Contribution of Emergency Departments to the Provision of Hospital
      Associated Health Care in the USA.
AB  - Traditional approaches to assessing the health of populations focus on the use of
      primary care and the delivery of care through patient-centered homes, managed
      care resources, and accountable care organizations. The use of emergency
      departments (EDs) has largely not been given consideration in these models. Our
      study aimed to determine the contribution of EDs to the health care received by
      Americans between 1996 and 2010 and to compare it with the contribution of
      outpatient and inpatient services using National Hospital Ambulatory Medical Care
      Survey and National Hospital Discharge Survey databases. We found that EDs
      contributed an average of 47.7% of the hospital-associated medical care delivered
      in the United States, and this percentage increased steadily over the 14-year
      study period. EDs are a major source of medical care in the United States,
      especially for vulnerable populations, and this contribution increased throughout
      the study period. Including emergency care within health reform and population
      health efforts would prove valuable to supporting the health of the nation.

PMID- 29039719
TI  - Resistance in In Vitro Selected Tigecycline-Resistant Methicillin-Resistant
      Staphylococcus aureus Sequence Type 5 Is Driven by Mutations in mepR and mepA
      Genes.
AB  - A tigecycline-susceptible (TGC-S) Sequence Type (ST) 5 clinical methicillin
      resistant Staphylococcus aureus (MRSA) strain was cultured in escalating levels
      of tigecycline, yielding mutants eightfold more resistant. Their genomes were
      sequenced to identify genetic alterations, resulting in resistance. Alterations
      in rpsJ, commonly related to tigecycline resistance, were also investigated.
      Tigecycline resistance was mediated by loss-of-function mutations in the
      transcriptional repressor mepR, resulting in derepression of the efflux pump
      mepA. Increased levels of resistance were obtained by successive mutations in
      mepA itself. No alterations in RpsJ were observed in selected strains, but we
      observed a K57M substitution, previously correlated with resistance, among TGC-S
      clinical strains. Thus, the pathway to tigecycline resistance in CC5 MRSA in
      vitro appears to be derepression of mep operon as the result of mepR loss-of
      function mutation, followed by alterations in MepA efflux pump. This shows that
      other evolutionary pathways, besides mutation of rpsJ, are available for evolving
      tigecycline resistance in CC5 MRSA.

PMID- 29039721
TI  - A recurrent splice-site mutation in EPHA2 causing congenital posterior nuclear
      cataract.
AB  - : Intoduction: Inherited cataract, opacification of the lens, is the most common
      worldwide cause of blindness in children. We aimed to identify the genetic cause
      of autosomal dominant (AD) posterior nuclear cataract in a four generation
      British family. METHODS: Whole genome sequence (WGS) was performed on two
      affected and one unaffected individual of the family and further validated by
      direct sequencing. Haplotype analysis was performed via genotying. RESULTS: A
      splice-site mutation c.2826-9G>A in the gene EPHA2, encoding EPH receptor A2 was
      identified and found to co-segregate with disease. CONCLUSIONS: We have
      identified a recurrent splice-site mutation c.2826-9G>A in EPHA2 causing isolated
      posterior nuclear cataract, providing evidence of further phenotypic
      heterogeneity associated with this variant.

PMID- 29039722
TI  - Instructional Insights: Restructuring the Fieldwork Experience: One Clinic's
      Journey.
AB  - Although there are standards for occupational therapy education, there are no
      universal standards for the affiliated fieldwork settings, only guidelines from
      the educational institutions. As a result, a student learning experience often
      varies dramatically from facility to facility. Several factors that may affect
      the clinical experience include the preparedness of a student, the willingness of
      a clinic to work through potential student challenges, and the theoretical
      foundation a clinic has built for disseminating occupational therapy practice
      skills. This article highlights the journey of one clinic through a redesign of
      the occupational therapy fieldwork program and outlines the steps taken to
      transform student experiences and improve program success. Starting with a self
      directed review of the fieldwork process, and through a combination of program
      redesign, application of a theoretical foundation, and refocus toward a
      competency-based program, the student success rate at this acute rehabilitation
      hospital drastically improved and achieved positive feedback from all involved.

PMID- 29039723
TI  - Glenohumeral internal rotation deficit in table tennis players.
AB  - Table tennis requires rapid and extreme movements that may result in shoulder
      adaptations, such as glenohumeral internal rotation deficit, which is a risk
      factor for several injuries. This study compared range of motion of internal and
      external rotation and total rotation motion of glenohumeral joint between
      dominant and non-dominant shoulders of table tennis players. This is a cross
      sectional observational study. Twenty healthy male table tennis players that were
      enrolled in an official table tennis league took part in this study (mean age:
      22.9 +/- 12.9 years, time of sports practice: 6.2 +/- 7.12 years). Measurements
      of passive glenohumeral external rotation and internal rotation were taken with
      the individuals in the supine and sidelying positions. Total rotation motion was
      calculated by summing external and internal rotations. The dominant side showed
      decreased internal rotation when compared to non-dominant side in both supine
      (mean difference: 14.9 degrees , p = 0.02) and sidelying positions (mean
      difference: 16.3 degrees , p = 0.01). No significant difference (p > 0.05) was
      found for external rotation and total rotation motion between dominant and non
      dominant shoulders. The findings indicate that table tennis players exhibit
      glenohumeral internal rotation deficit of dominant shoulder.

PMID- 29039724
TI  - Paravascular spaces at the brain surface: Low resistance pathways for
      cerebrospinal fluid flow.
AB  - Clearance of waste products from the brain is of vital importance. Recent
      publications suggest a potential clearance mechanism via paravascular channels
      around blood vessels. Arterial pulsations might provide the driving force for
      paravascular flow, but its flow pattern remains poorly characterized. In
      addition, the relationship between paravascular flow around leptomeningeal
      vessels and penetrating vessels is unclear. In this study, we determined blood
      flow and diameter pulsations through a thinned-skull cranial window. We observed
      that microspheres moved preferentially in the paravascular space of arteries
      rather than in the adjacent subarachnoid space or around veins. Paravascular flow
      was pulsatile, generated by the cardiac cycle, with net antegrade flow. Confocal
      imaging showed microspheres distributed along leptomeningeal arteries, while
      their presence along penetrating arteries was limited to few vessels. These data
      suggest that paravascular spaces around leptomeningeal arteries form low
      resistance pathways on the surface of the brain that facilitate cerebrospinal
      fluid flow.

PMID- 29039725
TI  - High-Risk Breast Lesions: A Machine Learning Model to Predict Pathologic Upgrade
      and Reduce Unnecessary Surgical Excision.
AB  - Purpose To develop a machine learning model that allows high-risk breast lesions
      (HRLs) diagnosed with image-guided needle biopsy that require surgical excision
      to be distinguished from HRLs that are at low risk for upgrade to cancer at
      surgery and thus could be surveilled. Materials and Methods Consecutive patients
      with biopsy-proven HRLs who underwent surgery or at least 2 years of imaging
      follow-up from June 2006 to April 2015 were identified. A random forest machine
      learning model was developed to identify HRLs at low risk for upgrade to cancer.
      Traditional features such as age and HRL histologic results were used in the
      model, as were text features from the biopsy pathologic report. Results One
      thousand six HRLs were identified, with a cancer upgrade rate of 11.4% (115 of
      1006). A machine learning random forest model was developed with 671 HRLs and
      tested with an independent set of 335 HRLs. Among the most important traditional
      features were age and HRL histologic results (eg, atypical ductal hyperplasia).
      An important text feature from the pathologic reports was "severely atypical."
      Instead of surgical excision of all HRLs, if those categorized with the model to
      be at low risk for upgrade were surveilled and the remainder were excised, then
      97.4% (37 of 38) of malignancies would have been diagnosed at surgery, and 30.6%
      (91 of 297) of surgeries of benign lesions could have been avoided. Conclusion
      This study provides proof of concept that a machine learning model can be applied
      to predict the risk of upgrade of HRLs to cancer. Use of this model could
      decrease unnecessary surgery by nearly one-third and could help guide clinical
      decision making with regard to surveillance versus surgical excision of HRLs. (c)
      RSNA, 2017.

PMID- 29039726
TI  - Perceived relevance mediates the relationship between professional identity and
      attitudes towards interprofessional education in first-year university students.
AB  - The strength of health science students' identification with their chosen
      profession is associated with their attitudes towards interprofessional education
      (IPE). However, little is known about the factors that might mediate this
      relationship. In this article, we examine the relationships between professional
      identification, communication and teamwork skills, perceived relevance of IPE,
      and positive and negative attitudes towards IPE. A sample of 444 first-year
      university students from 25 health science professions enrolled in a first-year
      interprofessional program participated in this research by completing a
      questionnaire. Data were analysed using path analysis. Positive IPE attitudes
      were more strongly endorsed than negative IPE attitudes. Perceived relevance of
      IPE to future careers was the strongest predictor of both positive and negative
      attitudes to IPE, and fully mediated the effect of professional identity. Self
      reported communication and teamwork skills were a significant negative predictor
      of negative attitudes to IPE only, and the effect was not mediated by perceived
      relevance. These findings indicate that IPE may be particularly challenging for
      students who do not have confidence in their abilities to communicate and work
      effectively in teams. Building these skills through alternative communication
      technologies may decrease negative attitudes. In order to maintain or increase
      positive attitudes towards IPE in introductory programs that span professions,
      the curriculum needs to be designed to demonstrate relevance to the future
      careers of participating students.

PMID- 29039727
TI  - Identification of Aptamers That Bind to Sickle Hemoglobin and Inhibit Its
      Polymerization.
AB  - The pathophysiology of sickle cell disease (SCD) is dependent on the
      polymerization of deoxygenated sickle hemoglobin (HbS), leading to erythrocyte
      deformation (sickling) and vaso-occlusion within the microvasculature. Following
      deoxygenation, there is a delay time before polymerization is initiated, during
      which nucleation of HbS monomers occurs. An agent with the ability to extend this
      delay time or slow polymerization would therefore hold a therapeutic, possibly
      curative, potential. We used the Systematic Evolution of Ligands by Exponential
      Enrichment (SELEX) method to screen for HbS-binding RNA aptamers modified with
      nuclease-resistant 2'-fluoropyrimidines. Polymerization assays were employed to
      identify aptamers with polymerization-inhibitory properties. Two noncompeting
      aptamers, DE3A and OX3B, were found to bind hemoglobin, significantly increase
      the delay time, and reduce the rate of polymerization of HbS. These modifiable,
      nuclease-resistant aptamers are potential new therapeutic agents for SCD.

PMID- 29039728
TI  - Maternal Smoking During Pregnancy and ADHD: Results From a Systematic Review and
      Meta-Analysis of Prospective Cohort Studies.
AB  - OBJECTIVE: Findings on maternal smoking during pregnancy and ADHD risk in
      children are inconsistent. A meta-analysis was performed to summarize effects of
      exposure to maternal smoking during pregnancy on ADHD risk in children. METHOD:
      We conducted a systematic literature search to select articles up to June 2016.
      Only prospective cohort studies were included. Summary relative risks (RRs) with
      95% confidence intervals (CIs) were calculated. RESULTS: Pooled RR estimates
      based on 12 cohort studies including 17,304 pregnant women suggested that
      maternal smoking during pregnancy was associated with an increased risk of ADHD
      (pooled RR = 1.58, 95% CI = [1.33, 1.88]). CONCLUSION: Results from this study
      indicate that maternal smoking during pregnancy is related to an increased risk
      of ADHD in children. There is an urgent need to increase maternal awareness of
      smoking risk and quitting smoking to mitigate the ADHD risk in children.

PMID- 29039729
TI  - Antimicrobial Activity of Ceftolozane-Tazobactam Tested Against
      Enterobacteriaceae and Pseudomonas aeruginosa with Various Resistance Patterns
      Isolated in U.S. Hospitals (2013-2016) as Part of the Surveillance Program:
      Program to Assess Ceftolozane-Tazobactam Susceptibility.
AB  - This study evaluated the in vitro activity of ceftolozane-tazobactam and
      comparator agents tested against Enterobacteriaceae and Pseudomonas aeruginosa
      isolates from hospitalized patients in the United States. Ceftolozane-tazobactam
      is an antipseudomonal cephalosporin combined with a well-established beta
      lactamase inhibitor. A total of 18,960 organisms (15,223 Enterobacteriaceae and
      3,737 P. aeruginosa) were consecutively collected from 32 medical centers located
      in all nine U.S. census divisions from 2013 to 2016. Organisms were tested for
      susceptibility by broth microdilution. CLSI and EUCAST interpretive criteria were
      used. Ceftolozane-tazobactam (94.4% susceptible), amikacin (99.0% susceptible),
      and meropenem (98.0% susceptible) were the most active compounds tested against
      Enterobacteriaceae. Among the Enterobacteriaceae isolates tested, 1.9% (n = 286)
      were carbapenem-resistant Enterobacteriaceae (CRE) and 9.5% (n = 1,450) exhibited
      an extended-spectrum beta-lactamase (ESBL) non-CRE phenotype. Although
      ceftolozane-tazobactam showed good activity against ESBL non-CRE phenotype
      strains of Enterobacteriaceae (87.5% susceptible), it lacked useful activity
      against CRE. Ceftolozane-tazobactam was the most potent beta-lactam agent tested
      against P. aeruginosa isolates, with 97.3% susceptible. Only colistin was more
      active, inhibiting 99.5% of isolates. Ceftolozane-tazobactam also maintained good
      activity against multidrug-resistant P. aeruginosa, with 88.6% susceptible.
      Ceftolozane-tazobactam was the most active beta-lactam agent tested against P.
      aeruginosa and was more active than available cephalosporins and piperacillin
      tazobactam against Enterobacteriaceae.

PMID- 29039731
TI  - Patchy DNA forms of the Zika virus RNA genome are generated following infection
      in mosquito cell cultures and in mosquitoes.
AB  - Zika virus (ZIKV) is a mosquito-borne flavivirus and has historically been
      reported to cause mild symptomatic diseases during human infections. More
      recently, the explosion of microcephaly among infants born to ZIKV-infected women
      has made ZIKV a global public health concern. While ZIKV causes acute human
      diseases, infections of vector mosquitoes are basically non-pathogenic, allowing
      persistent infections and conferring lifelong ability to transmit the virus.
      Recent studies have revealed that DNA forms of arboviral RNA genomes play a
      significant role in viral persistence in mosquitoes. We have initiated
      experiments to determine whether ZIKV generates viral DNA (vDNA) forms following
      infection in mosquitoes. Here we show that vDNAs are generated following ZIKV
      infection both in mosquito cell cultures and in its primary vector Aedes aegypti.
      vDNA formation is more extensive in RNA interference (RNAi)-deficient Aedes
      albopictus-derived C6/36 cells compared to RNAi-proficient mosquito cells. In
      addition, vDNAs are generated via multiple template-switching events.

PMID- 29039732
TI  - A provisional complete genome-based genotyping system for rotavirus species C
      from terrestrial mammals.
AB  - Rotaviruses C (RVCs) have been detected in pigs, humans, cows, ferrets and dogs.
      Despite their zoonotic impact and pathogenicity, the genetic characterization of
      RVCs is incomplete, unlike rotaviruses A (RVAs), whose genetics are well studied.
      Several studies reported partial and complete genomic sequences for multiple
      porcine and canine RVCs. We aimed to establish a complete genome-based genotyping
      system for RVCs, by analysing complete genome data from 22 porcine RVCs
      identified in Japan from 2002 to 2010, along with those from multiple human,
      bovine, porcine, canine and ferret RVCs reported in several previous studies.
      Comparative sequence analyses among RVCs from various host species demonstrated
      that porcine RVCs had a high level of genetic diversity. In addition,
      phylogenetic analyses of all 11 RNA segments indicated that porcine RVCs could be
      classified into multiple genotypes. Notably, the VP4 dendrogram divided bovine
      RVCs into multiple genotypes. Consequently, the provisional genotype
      classification for RVCs from terrestrial mammals revealed the existence of
      genotypes 18G, 21P, 13I, 4R, 6C, 6M, 9A, 8N, 6T, 5E and 4H for the genes VP7,
      VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively, based on
      the cut-off values as defined by the Rotavirus Classification Working Group. The
      system established in this study deepens our understanding of RVC evolution and
      facilitates the discovery of genetic events (gene reassortment and interspecies
      transmission) among RVCs.

PMID- 29039733
TI  - Near-infrared fluorescent protein iRFP720 is optimal for in vivo fluorescence
      imaging of rabies virus infection.
AB  - In vivo imaging is a noninvasive method that enables real-time monitoring of
      viral infection dynamics in a small animal, which allows a better understanding
      of viral pathogenesis. In vivo bioluminescence imaging of virus infection is
      widely used but, despite its advantage over bioluminescence that no substrate
      administration is required, fluorescence imaging is not used because of severe
      autofluorescence. Recently, several far-red and near-infrared (NIR) fluorescent
      proteins (FPs) have been developed and shown to be useful for whole-body
      fluorescence imaging. Here, we report comparative testing of far-red and NIR FPs
      in the imaging of rabies virus (RABV) infection. Using the highly neuroinvasive
      1088 strain, we generated recombinant RABV that expressed FPs such as Katushka2S,
      E2-Crimson, iRFP670 or iRFP720. After intracerebral inoculation to nude mice, the
      1088 strain expressing iRFP720, the most red-shifted FP, was detected the
      earliest with the highest signal-to-noise ratio using a filter set for >700 nm,
      in which the background signal level was very low. Furthermore, we could also
      track viral dissemination from the spinal cord to the brain in nude mice after
      intramuscular inoculation of iRFP720-expressing 1088 into the hind limb. Hence,
      we conclude that the NIR FP iRFP720 used with a filter set for >700 nm is useful
      for in vivo fluorescence imaging not only for RABV infection but also for other
      virus infections. Our findings will also be useful for developing dual-optical
      imaging of virus-host interaction dynamics using bioluminescence reporter mice
      for inflammation imaging.

PMID- 29039734
TI  - Computational analysis of a species D human adenovirus provides evidence of a
      novel virus.
AB  - A human adenovirus (HAdV) species D, was isolated from a hospitalised child with
      severe lower respiratory infection. It was initially detected in the
      nasopharyngeal aspirate of the child followed by conventional PCR amplification
      of the hexon, penton base, and fibre genes. Sanger DNA sequencing and
      phylogenetic analyses showed characteristics of a recombinant genome not
      described before. Next Generation Sequencing analysis was performed to
      reconstruct its complete DNA genome after viral isolation in adenocarcinoma human
      cell line (A549). A complete genomic sequence of 35.2 kb in length, with a G+C
      content of 57 % was obtained, related to HAdV-D29 (96 % identity). Imputed
      serology analysis demonstrated its novel type with a nucleotide sequence identity
      of 95.3 % (hexon loop 1) and 96 % (hexon loop 2) to HAdV-D9. The penton base gene
      showed a novel sequence, distantly related to HAdV-D44. The E3 and E4 regions
      evolved significantly from their ancestors. The fibre gene was almost identical
      to the knob region of HAdV-D15 but showed an unrelated shaft sequence. In
      conclusion the genomics of this novel HAdV, designated the HAdV-D83 [P83H9F15]
      prototype and bearing a new penton base gene, supports the importance of viral
      evolution to understand modified tissue tropism, enhanced transmission, or
      altered virulence.

PMID- 29039735
TI  - Correction: Palmitoylated SCP1 is targeted to the plasma membrane and negatively
      regulates angiogenesis.

PMID- 29039737
TI  - Onsager's missing steps retraced.
AB  - Onsager's paper on phase transition and phase coexistence in anisotropic
      colloidal systems is a landmark in the theory of lyotropic liquid crystals.
      However, an uncompromising scrutiny of Onsager's original derivation reveals that
      it would be rigorously valid only for ludicrous values of the system's number
      density (of the order of the reciprocal of the number of particles). Based on
      Penrose's tree identity and an appropriate variant of the mean-field approach for
      purely repulsive, hard-core interactions, our theory shows that Onsager's theory
      is indeed valid for a reasonable range of densities.

PMID- 29039738
TI  - Vacancies and holes in bulk and at 180 degrees  domain walls in lead titanate.
AB  - Domain walls (DWs) in ferroic materials exhibit a plethora of unexpected
      properties that are different from the adjacent ferroic domains. Still, the
      intrinsic/extrinsic origin of these properties remains an open question. Here,
      density functional theory calculations are used to investigate the interaction
      between vacancies and 180 degrees  DWs in the prototypical ferroelectric PbTiO3,
      with a special emphasis on cationic vacancies and released holes. All vacancies
      are more easily formed within the DW than in the domains. This is interpreted,
      using a phenomenological model, as the partial compensation of an extra-tensile
      stress when the defect is created inside the DW. Oxygen vacancies are found to be
      always fully ionized, independently of the thermodynamic conditions, while
      cationic vacancies can be either neutral or partially ionized (oxygen-rich
      conditions), or fully ionized (oxygen-poor conditions). Therefore, in oxidizing
      conditions, holes are induced by neutral and partially ionized Pb vacancies. In
      the bulk PbTiO3, these holes are more stable as delocalized rather than small
      polarons, but at DWs, the two forms are found to be possible.

PMID- 29039736
TI  - A novel central nervous system-penetrating protease inhibitor overcomes human
      immunodeficiency virus 1 resistance with unprecedented aM to pM potency.
AB  - Antiretroviral therapy for HIV-1 infection/AIDS has significantly extended the
      life expectancy of HIV-1-infected individuals and reduced HIV-1 transmission at
      very high rates. However, certain individuals who initially achieve viral
      suppression to undetectable levels may eventually suffer treatment failure mainly
      due to adverse effects and the emergence of drug-resistant HIV-1 variants. Here,
      we report GRL-142, a novel HIV-1 protease inhibitor containing an unprecedented 6
      5-5-ring-fused crown-like tetrahydropyranofuran, which has extremely potent
      activity against all HIV-1 strains examined with IC50 values of attomolar-to
      picomolar concentrations, virtually no effects on cellular growth, extremely high
      genetic barrier against the emergence of drug-resistant variants, and favorable
      intracellular and central nervous system penetration. GRL-142 forms optimum
      polar, van der Waals, and halogen bond interactions with HIV-1 protease and
      strongly blocks protease dimerization, demonstrating that combined multiple
      optimizing elements significantly enhance molecular and atomic interactions with
      a target protein and generate unprecedentedly potent and practically favorable
      agents.

PMID- 29039739
TI  - Charge-transfer modified embedded atom method dynamic charge potential for Li-Co
      O system.
AB  - To overcome the limitation of conventional fixed charge potential methods for the
      study of Li-ion battery cathode materials, a dynamic charge potential method,
      charge-transfer modified embedded atom method (CT-MEAM), has been developed and
      applied to the Li-Co-O ternary system. The accuracy of the potential has been
      tested and validated by reproducing a variety of structural and electrochemical
      properties of LiCoO2. A detailed analysis on the local charge distribution
      confirmed the capability of this potential for dynamic charge modeling. The
      transferability of the potential is also demonstrated by its reliability in
      describing Li-rich Li2CoO2 and Li-deficient LiCo2O4 compounds, including their
      phase stability, equilibrium volume, charge states and cathode voltages. These
      results demonstrate that the CT-MEAM dynamic charge potential could help to
      overcome the challenge of modeling complex ternary transition metal oxides. This
      work can promote molecular dynamics studies of Li ion cathode materials and other
      important transition metal oxides systems that involve complex electrochemical
      and catalytic reactions.

PMID- 29039740
TI  - Structure, magnetism and electronic properties in 3<i>d</i>-5<i>d</i> based
      double perovskite (Sr<sub>1-x</sub>Y<sub>x</sub>)<sub>2</sub>FeIrO<sub>6</sub>.
AB  - The 3$d$-5$d$ based double perovskites are of current interest as they provide
      model system to study the interplay between electronic correlation ($U$) and spin
      orbit coupling (SOC). Here we report detailed structural, magnetic and transport
      properties of doped double perovskite material (Sr$_{1-x}$Y$_x$)$_2$FeIrO$_6$
      with $x$ $?leq$ 0.2. With substitution of Y, system retains its original crystal
      structure but structural parameters modify with $x$ in nonmonotonic fashion. The
      magnetization data for Sr$_2$FeIrO$_6$ show antiferromagnetic type magnetic
      transition around 45 K, however, a close inspection in data indicates a weak
      magnetic phase transition around 120 K. No change of structural symmetry has been
      observed down to low temperature, although the lattice parameters show sudden
      changes around the magnetic transitions. Sr$_2$FeIrO$_6$ shows an insulating
      behavior over the whole temperature range which yet does not change with Y
      substitution. Nature of charge conduction is found to follow thermally activated
      Mott's variable range hopping and power law behavior for parent and doped
      samples, respectively. Interestingly, evolution of structural, magnetic and
      transport behavior in (Sr$_{1-x}$Y$_x$)$_2$FeIrO$_6$ is observed to reverse with
      $x$ $>$ 0.1 which is believed to arise due to change in transition metal ionic
      state.

PMID- 29039741
TI  - Passivation of black phosphorus saturable absorbers for reliable pulse formation
      of fiber lasers.
AB  - Black phosphorus (BP) has attracted increasing attention due to its unique
      electrical properties. In addition, the outstanding optical nonlinearity of BP
      has been demonstrated in various ways. Its functionality as a saturable absorber,
      in particular, has been validated in demonstrations of passive mode-locked
      lasers. However, normally, the performance of BP is degraded eventually by both
      thermal and chemical damage in ambient conditions. The passivation of BP is the
      critical issue to guarantee a stable performance of the optical devices. We
      quantitatively characterized the mode-locked lasers operated by BP saturable
      absorbers with diversified passivation materials such as polydimethylsiloxane
      (PDMS) or Al2O3, considering the atomic structure of the materials, and therefore
      the hydro-permeability of the passivation layers. Unlike the BP layers without
      passivation, we demonstrated that the Al2O3-passivated BP layer was protected
      from the surface oxidation reaction in the long-term, and the PDMS-passivated one
      had a short-term blocking effect. The quantitative analysis showed that the time
      dependent characteristics of the pulsed laser without passivation were changed
      with respect to the pulse duration, spectral width, and time-bandwidth product
      displaying 550 fs, 2.8 nm, and 0.406, respectively. With passivation, the changes
      were limited to <43 fs, <0.3 nm, and <0.012, respectively.

PMID- 29039743
TI  - Bioactivity and Cell Compatibility of beta-Wollastonite Derived from Rice Husk
      Ash and Limestone.
AB  - The aim of this study was to prepare beta-wollastonite using a green synthesis
      method (autoclaving technique) without organic solvents and to study its
      bioactivity. To prepare beta-wollastonite, the precursor ratio of CaO:SiO2 was
      set at 55:45. This mixture was autoclaved for 8 h and later sintered at 950 
      degrees C for 2 h. The chemical composition of the precursors was studied using X
      ray fluorescence (XRF), in which rice husk ash consists of 89.5 wt % of SiO2 in a
      cristobalite phase and calcined limestone contains 97.2 wt % of CaO. The X-ray
      diffraction (XRD) patterns after sintering showed that only beta-wollastonite was
      detected as the single phase. To study its bioactivity and degradation
      properties, beta-wollastonite samples were immersed in simulated body fluid (SBF)
      for various periods of time. Throughout the soaking period, the molar ratio of
      Ca/P obtained was in the range of 1.19 to 2.24, and the phase detected was
      amorphous calcium phosphate, which was confirmed by scanning electron microscope
      with energy dispersive X-ray analysis (SEM/EDX) and XRD. Fourier-transform
      infrared spectroscopy (FTIR) analysis indicated that the peaks of the calcium and
      phosphate ions increased when an amorphous calcium phosphate layer was formed on
      the surface of the beta-wollastonite sample. A cell viability and proliferation
      assay test was performed on the rice husk ash, calcined limestone, and beta
      wollastonite samples by scanning electron microscope. For heavy metal element
      evaluation, a metal panel that included As, Cd, Pb, and Hg was selected, and both
      precursor and beta-wollastonite fulfilled the requirement of an American Society
      for Testing and Materials (ASTM F1538-03) standard specification. Apart from
      that, a degradation test showed that the loss of mass increased incrementally as
      a function of soaking period. These results showed that the beta-wollastonite
      materials produced from rice husk ash and limestone possessed good bioactivity,
      offering potential for biomedical applications.

PMID- 29039742
TI  - Disease-Related Detection with Electrochemical Biosensors: A Review.
AB  - Rapid diagnosis of diseases at their initial stage is critical for effective
      clinical outcomes and promotes general public health. Classical in vitro
      diagnostics require centralized laboratories, tedious work and large, expensive
      devices. In recent years, numerous electrochemical biosensors have been developed
      and proposed for detection of various diseases based on specific biomarkers
      taking advantage of their features, including sensitivity, selectivity, low cost
      and rapid response. This article reviews research trends in disease-related
      detection with electrochemical biosensors. Focus has been placed on the
      immobilization mechanism of electrochemical biosensors, and the techniques and
      materials used for the fabrication of biosensors are introduced in details.
      Various biomolecules used for different diseases have been listed. Besides, the
      advances and challenges of using electrochemical biosensors for disease-related
      applications are discussed.

PMID- 29039744
TI  - Implementing a Multidisciplinary Tumor Board in the Community Practice Setting.
AB  - : Multidisciplinary tumor boards are an opportunity for radiologists to
      demonstrate value to referring clinicians, the hospital, and patients.
      Multidisciplinary tumor boards are commonly utilized in academic institutions,
      but may not be readily available in community practice. We discuss strategies
      academic radiologists may employ to assist in the implementation of a
      multidisciplinary tumor board in the community practice setting. SUMMARY:
      Strategies to assist in the implementation of a multidisciplinary tumor board in
      the community practice setting are described.

PMID- 29039745
TI  - Profiling the Fatty Acids Content of Ornamental Camellia Seeds Cultivated in
      Galicia by an Optimized Matrix Solid-Phase Dispersion Extraction.
AB  - Camellia (genus of flowering plants of fam. Theaceae) is one of the main crops in
      Asia, where tea and oil from leaves and seeds have been utilized for thousands of
      years. This plant is excellently adapted to the climate and soil of Galicia
      (northwestern Spain) and northern Portugal where it is grown not only as an
      ornamental plant, but to be evaluated as a source of bioactive compounds. In this
      work, the main fatty acids were extracted from Camellia seeds of four varieties
      of Camellia: sasanqua, reticulata, japonica and sinensis, by means of matrix
      solid phase dispersion (MSPD), and analyzed by gas chromatography (GC) with MS
      detection of the corresponding methyl esters. MSPD constitutes an efficient and
      greener alternative to conventional extraction techniques, moreover if it is
      combined with the use of green solvents such as limonene. The optimization of the
      MSPD extraction procedure has been conducted using a multivariate approach based
      on strategies of experimental design, which enabled the simultaneous evaluation
      of the factors influencing the extraction efficiency as well as interactions
      between factors. The optimized method was applied to characterize the fatty acids
      profiles of four Camellia varieties seeds, allowing us to compare their fatty
      acid composition.

PMID- 29039746
TI  - Preclinical Testing of an Oncolytic Parvovirus: Standard Protoparvovirus H-1PV
      Efficiently Induces Osteosarcoma Cell Lysis In Vitro.
AB  - Osteosarcoma is the most frequent malignant disease of the bone. On the basis of
      early clinical experience in the 1960s with H-1 protoparvovirus (H-1PV) in
      osteosarcoma patients, this effective oncolytic virus was selected for systematic
      preclinical testing on various osteosarcoma cell cultures. A panel of five human
      osteosarcoma cell lines (CAL 72, H-OS, MG-63, SaOS-2, U-2OS) was tested. Virus
      oncoselectivity was confirmed by infecting non-malignant human neonatal
      fibroblasts and osteoblasts used as culture models of non-transformed mesenchymal
      cells. H-1PV was found to enter osteosarcoma cells and to induce viral DNA
      replication, transcription of viral genes, and translation to viral proteins.
      After H-1PV infection, release of infectious viral particles from osteosarcoma
      cells into the supernatant indicated successful viral assembly and egress.
      Crystal violet staining revealed progressive cytomorphological changes in all
      osteosarcoma cell lines. Infection of osteosarcoma cell lines with the standard H
      1PV caused an arrest of the cell cycle in the G2 phase, and these lines had a
      limited capacity for standard H-1PV virus replication. The cytotoxicity of wild
      type H-1PV virus towards osteosarcoma cells was compared in vitro with that of
      two variants, Del H-1PV and DM H-1PV, previously described as fitness variants
      displaying higher infectivity and spreading in human transformed cell lines of
      different origins. Surprisingly, wild-type H-1PV displayed the strongest
      cytostatic and cytotoxic effects in this analysis and thus seems the most
      promising for the next preclinical validation steps in vivo.

PMID- 29039748
TI  - Experimental and Computational Study of Ductile Fracture in Small Punch Tests.
AB  - A unified experimental-computational study on ductile fracture initiation and
      propagation during small punch testing is presented. Tests are carried out at
      room temperature with unnotched disks of different thicknesses where large-scale
      yielding prevails. In thinner specimens, the fracture occurs with severe necking
      under membrane tension, whereas for thicker ones a through thickness shearing
      mode prevails changing the crack orientation relative to the loading direction.
      Computational studies involve finite element simulations using a shear modified
      Gurson-Tvergaard-Needleman porous plasticity model with an integral-type nonlocal
      formulation. The predicted punch load-displacement curves and deformed profiles
      are in good agreement with the experimental results.

PMID- 29039747
TI  - Development of Useful Biomaterial for Bone Tissue Engineering by Incorporating
      Nano-Copper-Zinc Alloy (nCuZn) in Chitosan/Gelatin/Nano-Hydroxyapatite
      (Ch/G/nHAp) Scaffold.
AB  - Ceramic and metallic nanoparticles can improve the mechanical and biological
      properties of polymeric scaffolds for bone tissue engineering (BTE). In this
      work, nanohydroxyapatite (nHAp) and nano-copper-zinc alloy (nCuZn) were added to
      a chitosan/gelatin (Ch/G) scaffold in order to investigate the effects on
      morphological, physical, and biocompatibility properties. Scaffolds were
      fabricated by a freeze-drying technique using different pre-freezing
      temperatures. Microstructure and morphology were studied by scanning electron
      microscopy (SEM), glass transition (Tg) was studied using differential scanning
      calorimetry (DSC), cell growth was estimated by MTT assay, and biocompatibility
      was examined in vitro and in vivo by histochemistry analyses. Scaffolds and
      nanocomposite scaffolds presented interconnected pores, high porosity, and pore
      size appropriate for BTE. Tg of Ch/G scaffolds was diminished by nanoparticle
      inclusion. Mouse embryonic fibroblasts (MEFs) cells loaded in the Ch/G/nHAp/nCuZn
      nanocomposite scaffold showed suitable behavior, based on cell adhesion, cell
      growth, alkaline phosphatase (ALP) activity as a marker of osteogenic
      differentiation, and histological in vitro cross sections. In vivo subcutaneous
      implant showed granulation tissue formation and new tissue infiltration into the
      scaffold. The favorable microstructure, coupled with the ability to integrate
      nanoparticles into the scaffold by freeze-drying technique and the
      biocompatibility, indicates the potential of this new material for applications
      in BTE.

PMID- 29039749
TI  - Bionic Design, Materials and Performance of Bone Tissue Scaffolds.
AB  - Design, materials, and performance are important factors in the research of bone
      tissue scaffolds. This work briefly describes the bone scaffolds and their
      anatomic structure, as well as their biological and mechanical characteristics.
      Furthermore, we reviewed the characteristics of metal materials, inorganic
      materials, organic polymer materials, and composite materials. The importance of
      the bionic design in preoperative diagnosis models and customized bone scaffolds
      was also discussed, addressing both the bionic structure design (macro and micro
      structure) and the bionic performance design (mechanical performance and
      biological performance). Materials and performance are the two main problems in
      the development of customized bone scaffolds. Bionic design is an effective way
      to solve these problems, which could improve the clinical application of bone
      scaffolds, by creating a balance between mechanical performance and biological
      performance.

PMID- 29039750
TI  - Modeling of Body Weight Metrics for Effective and Cost-Efficient Conventional
      Factor VIII Dosing in Hemophilia A Prophylaxis.
AB  - The total body weight-based dosing strategy currently used in the prophylactic
      treatment of hemophilia A may not be appropriate for all populations. The
      assumptions that guide weight-based dosing are not valid in overweight and obese
      populations, resulting in overdosing and ineffective resource utilization. We
      explored different weight metrics including lean body weight, ideal body weight,
      and adjusted body weight to determine an alternative dosing strategy that is both
      safe and resource-efficient in normal and overweight/obese adult patients. Using
      a validated population pharmacokinetic model, we simulated a variety of dosing
      regimens using different doses, weight metrics, and frequencies; we also
      investigated the implications of assuming various levels of endogenous factor
      production. Ideal body weight performed the best across all of the regimens
      explored, maintaining safety while moderating resource consumption for overweight
      and obese patients.

PMID- 29039752
TI  - Aesthetic Diagnosis in Gestalt Therapy.
AB  - The diagnostic process in psychotherapy using the aesthetic evaluation is
      described in this article. Unlike the classical diagnostic process, which
      presents a result of comparing clinicians' observations with a diagnostic system
      (DSM, ICD, etc.), the aesthetic evaluation is a pre-reflexive, embodied, and
      preverbal process. A Gestalt Therapy theoretical frame is used to introduce a
      concept of the aesthetic diagnostic process. During this process, the clinicians
      use their own here-and-now presence, which takes part in the co-creation of the
      shared relational field during the therapeutic session. A specific procedure of
      the aesthetic evaluation is introduced. The clinical work with depressed clients
      is presented to illustrate this perspective.

PMID- 29039751
TI  - A Review: Expression of Aquaporins in Otitis Media.
AB  - Otitis media (OM) refers to inflammatory diseases of the middle ear (ME),
      regardless of cause or pathological mechanism. Among the molecular biological
      studies assessing the pathology of OM are investigations of the expression of
      aquaporins (AQPs) in the ME and Eustachian tube (ET). To date, fifteen studies
      have evaluated AQPs expression in the ME and ET. Although the expression of
      individual AQPs varies by species and model, eleven types of AQP, AQP1 to AQP11,
      were found to be expressed in mammalian ME and ET. The review showed that: (1)
      various types of AQPs are expressed in the ME and ET; (2) AQP expression may vary
      by species; and (3) the distribution and levels of expression of AQPs may depend
      on the presence or absence of inflammation, with variations even in the same
      species and same tissue. Fluid accumulation in the ME and ET is a common
      pathological mechanism for all types of OM, causing edema in the tissue and
      inducing inflammation, thereby possibly involving various AQPs. The expression
      patterns of several AQPs, especially AQP1, 4 and 5, were found to be altered in
      response to inflammatory stimuli, including lipopolysaccharide (LPS), suggesting
      that AQPs may have immunological functions in OM.

PMID- 29039753
TI  - PMA-Induced THP-1 Macrophage Differentiation is Not Impaired by Citrate-Coated
      Platinum Nanoparticles.
AB  - The innate immune system consists of several complex cellular and molecular
      mechanisms. During inflammatory responses, blood-circulating monocytes are driven
      to the sites of inflammation, where they differentiate into tissue macrophages.
      The research of novel nanomaterials applied to biomedical sciences is often
      limited by their toxicity or dangerous interactions with the immune cell
      functions. Platinum nanoparticles (PtNPs) have shown efficient antioxidant
      properties within several cells, but information on their potential harmful role
      in the monocyte-to-macrophage differentiation process is still unknown. Here, we
      studied the morphology and the release of cytokines in PMA-differentiated THP-1
      pre-treated with 5 nm PtNPs. Although NP endocytosis was evident, we did not find
      differences in the cellular structure or in the release of inflammatory cytokines
      and chemokines compared to cells differentiated in PtNP-free medium. However, the
      administration of PtNPs to previously differentiated THP-1 induced massive
      phagocytosis of the PtNPs and a slight metabolism decrease at higher doses.
      Further investigation using undifferentiated and differentiated neutrophil-like
      HL60 confirmed the harmlessness of PtNPs with non-adherent innate immune cells.
      Our results demonstrate that citrate-coated PtNPs are not toxic with these immune
      cell lines, and do not affect the PMA-stimulated THP-1 macrophage differentiation
      process in vitro.

PMID- 29039754
TI  - The NAC Transcription Factor Gene OsY37 (ONAC011) Promotes Leaf Senescence and
      Accelerates Heading Time in Rice.
AB  - Leaf senescence is an important physiological process involving the degradation
      of a number of metabolites and their remobilization to new reproductive and
      storage organs. NAC (NAM, ATAF, and CUC) transcription factors are reported as
      important regulators of the senescence process. Here, we describe the
      identification and functional characterization of the NAC transcription factor
      gene, OsY37 (Oryza sativa Yellow37, ONAC011) obtained from Oryza sativa cv.
      indica, and japonica. We created transgenic plants expressing the OsY37 gene
      under the control of a strong and constitutive CaMV35S promoter. The resulting
      transgenic plants overexpressing OsY37 gene showed early heading and precocious
      senescence phenotype of flag leaves compared with wild-type plants. By contrast,
      blocking the function of this gene via RNAi (RNA interference) and CRES-T
      (Chimeric Repressor Silencing Technology) technology, delayed both heading time
      and leaf senescence. Furthermore, knockdown of OsY37 expression caused dwarfism
      and high accumulation of chlorophyll during the vegetative phase. Irrespective of
      early or delayed senescence, transgenic plants showed reduced grain yields. Our
      results indicate that OsY37 acts as a positive regulator of heading and
      senescence during the reproductive phase in rice. In addition, OsY37 may be
      involved in plant development and grain yield.

PMID- 29039755
TI  - Comparing RIEGL RiCOPTER UAV LiDAR Derived Canopy Height and DBH with Terrestrial
      LiDAR.
AB  - In recent years, LIght Detection And Ranging (LiDAR) and especially Terrestrial
      Laser Scanning (TLS) systems have shown the potential to revolutionise forest
      structural characterisation by providing unprecedented 3D data. However, manned
      Airborne Laser Scanning (ALS) requires costly campaigns and produces relatively
      low point density, while TLS is labour intense and time demanding. Unmanned
      Aerial Vehicle (UAV)-borne laser scanning can be the way in between. In this
      study, we present first results and experiences with the RIEGL RiCOPTER with VUX
      (r) -1UAV ALS system and compare it with the well tested RIEGL VZ-400 TLS system.
      We scanned the same forest plots with both systems over the course of two days.
      We derived Digital Terrain Model (DTMs), Digital Surface Model (DSMs) and finally
      Canopy Height Model (CHMs) from the resulting point clouds. ALS CHMs were on
      average 11.5 c m higher in five plots with different canopy conditions. This
      showed that TLS could not always detect the top of canopy. Moreover, we extracted
      trunk segments of 58 trees for ALS and TLS simultaneously, of which 39 could be
      used to model Diameter at Breast Height (DBH). ALS DBH showed a high agreement
      with TLS DBH with a correlation coefficient of 0.98 and root mean square error of
      4.24 c m . We conclude that RiCOPTER has the potential to perform comparable to
      TLS for estimating forest canopy height and DBH under the studied forest
      conditions. Further research should be directed to testing UAV-borne LiDAR for
      explicit 3D modelling of whole trees to estimate tree volume and subsequently
      Above-Ground Biomass (AGB).

PMID- 29039756
TI  - Creative Arts Therapies as Temporary Home for Refugees: Insights from Literature
      and Practice.
AB  - One of the frequently overlooked psychosocial problems of refugees is the
      phenomenon of homesickness. Being forced into exile and unable to return home may
      cause natural feelings of nostalgia but may also result in emotional, cognitive,
      behavioral and physical adversities. According to the literature, the creative
      arts therapies with their attention to preverbal language-music, imagery, dance,
      role play, and movement-are able to reach individuals through the senses and
      promote successive integration, which can lead to transformation and therapeutic
      change. These forms of therapy can be a temporary home for refugees in the
      acculturation process, by serving as a safe and enactive transitional space. More
      specifically, working with dance and movement can foster the experience of the
      body as a home and thus provide a safe starting place, from which to regulate
      arousal, increase interoception, and symbolize trauma- and resource-related
      processes. Hearing, playing, and singing music from the home culture may assist
      individuals in maintaining their cultural and personal individuality. Creating
      drawings, paintings, or sculpturing around the topics of houses and environments
      from the past can help refugees to retain their identity through art, creating
      safe spaces for the future helps to look ahead, retain resources, and regain
      control. This article provides a literature review related to home and
      homesickness, and the role the arts therapies can play for refugees in
      transition. It further reports selected interview data on adverse life events and
      burdens in the host country from a German study. We propose that the creative
      arts therapies are not only a container that offers a temporary home, but can
      also serve as a bridge that gently guides refugees to a stepwise integration in
      the host country. Several clinical and research examples are presented suggesting
      that the support and affirmation through the creative arts can strengthen
      individuals in their process of moving from an old to a new environment.

PMID- 29039757
TI  - Data Access Based on a Guide Map of the Underwater Wireless Sensor Network.
AB  - Underwater wireless sensor networks (UWSNs) represent an area of increasing
      research interest, as data storage, discovery, and query of UWSNs are always
      challenging issues. In this paper, a data access based on a guide map (DAGM)
      method is proposed for UWSNs. In DAGM, the metadata describes the abstracts of
      data content and the storage location. The center ring is composed of nodes
      according to the shortest average data query path in the network in order to
      store the metadata, and the data guide map organizes, diffuses and synchronizes
      the metadata in the center ring, providing the most time-saving and energy
      efficient data query service for the user. For this method, firstly the data is
      stored in the UWSN. The storage node is determined, the data is transmitted from
      the sensor node (data generation source) to the storage node, and the metadata is
      generated for it. Then, the metadata is sent to the center ring node that is the
      nearest to the storage node and the data guide map organizes the metadata,
      diffusing and synchronizing it to the other center ring nodes. Finally, when
      there is query data in any user node, the data guide map will select a center
      ring node nearest to the user to process the query sentence, and based on the
      shortest transmission delay and lowest energy consumption, data transmission
      routing is generated according to the storage location abstract in the metadata.
      Hence, specific application data transmission from the storage node to the user
      is completed. The simulation results demonstrate that DAGM has advantages with
      respect to data access time and network energy consumption.

PMID- 29039758
TI  - X-pert MTB/RIF(r) Diagnosis of Twin Infants with Tuberculosis in Da Nang, Viet
      Nam.
AB  - 4-month-old twins were diagnosed with X-pert MTB/RIF(r) confirmed tuberculosis
      (TB)[...].

PMID- 29039759
TI  - A DFT Study of the Geometrical, Spectroscopical and Reactivity Properties of
      Diindolylmethane-Phenylboronic Acid Hybrids.
AB  - The structure of the ortho-, meta- and para- hybrid diindolylmethane
      phenylboronic acids and their interactions were optimized with by a quantum
      chemical method, using density functional theory at the (DFT) level. Thus,
      infrared bands were assigned based on the scaled theoretical wavenumbers by
      correlating the respective experimental data of the molecules. In addition, the
      corresponding 1H-/13C-/11B-NMR experimental and theoretical chemical shifts were
      correlated. The target molecules showed a poor treatment of the OH shifts in the
      GIAO method due to the absence of explicit solvent effects in these calculations;
      therefore, they were explicitly considered with acetone molecules. Moreover, the
      electron density at the hydrogen bond critical point increased, generating
      stabilization energy, from weak to moderate or weak to strong, serving as an
      indicator of the strength of the hydrogen bond between the different
      intermolecular interactions. Finally, some properties related to the reactive
      behavior of the target molecules associated with their cytotoxic effects and
      metabolic pathways were also calculated.

PMID- 29039760
TI  - Sea Cucumber Glycosides: Chemical Structures, Producing Species and Important
      Biological Properties.
AB  - Sea cucumbers belonging to echinoderm are traditionally used as tonic food in
      China and other Asian countries. They produce abundant biologically active
      triterpene glycosides. More than 300 triterpene glycosides have been isolated and
      characterized from various species of sea cucumbers, which are classified as
      holostane and nonholostane depending on the presence or absence of a specific
      structural unit gamma(18,20)-lactone in the aglycone. Triterpene glycosides
      contain a carbohydrate chain up to six monosaccharide units mainly consisting of
      d-xylose, 3-O-methy-d-xylose, d-glucose, 3-O-methyl-d-glucose, and d-quinovose.
      Cytotoxicity is the common biological property of triterpene glycosides isolated
      from sea cucumbers. Besides cytotoxicity, triterpene glycosides also exhibit
      antifungal, antiviral and hemolytic activities. This review updates and
      summarizes our understanding on diverse chemical structures of triterpene
      glycosides from various species of sea cucumbers and their important biological
      activities. Mechanisms of action and structural-activity relationships (SARs) of
      sea cucumber glycosides are also discussed briefly.

PMID- 29039761
TI  - AuPd Bimetallic Nanocrystals Embedded in Magnetic Halloysite Nanotubes: Facile
      Synthesis and Catalytic Reduction of Nitroaromatic Compounds.
AB  - In this research, a facile and effective approach was developed for the
      preparation of well-designed AuPd alloyed catalysts supported on magnetic
      halloysite nanotubes (HNTs@Fe3O4@AuPd). The microstructure and the magnetic
      properties of HNTs@Fe3O4@AuPd were confirmed by transmission electron microscopy
      (TEM), high resolution TEM (HRTEM), energy-dispersive X-ray spectroscopy (EDS),
      and vibrating sample magnetometry (VSM) analyses. The catalysts, fabricated by a
      cheap, environmentally friendly, and simple surfactant-free formation process,
      exhibited high activities during the reduction of 4-nitrophenol and various other
      nitroaromatic compounds. Moreover, the catalytic activities of the
      HNTs@Fe3O4@AuPd nanocatalysts were tunable via adjusting the atomic ratio of AuPd
      during the synthesis. As compared with the monometallic nanocatalysts
      (HNTs@Fe3O4@Au and HNTs@Fe3O4@Pd), the bimetallic alloyed HNTs@Fe3O4@AuPd
      nanocatalysts exhibited excellent catalytic activities toward the reduction of 4
      nitrophenol (4-NP) to 4-aminophenol. Furthermore, the as-obtained HNTs@Fe3O4@AuPd
      can be recycled several times, while retaining its functionality due to the
      stability and magnetic separation property.

PMID- 29039763
TI  - Design of a Wireless Sensor System with the Algorithms of Heart Rate and Agility
      Index for Athlete Evaluation.
AB  - Athlete evaluation systems can effectively monitor daily training and boost
      performance to reduce injuries. Conventional heart-rate measurement systems can
      be easily affected by artifact movement, especially in the case of athletes.
      Significant noise can be generated owing to high-intensity activities. To improve
      the comfort for athletes and the accuracy of monitoring, we have proposed to
      combine robust heart rate and agility index monitoring algorithms into a small,
      light, and single node. A band-pass-filter-based R-wave detection algorithm was
      developed. The agility index was calculated by preprocessing with band-pass
      filtering and employing the zero-crossing detection method. The evaluation was
      conducted under both laboratory and field environments to verify the accuracy and
      reliability of the algorithm. The heart rate and agility index measurements can
      be wirelessly transmitted to a personal computer in real time by the ZigBee
      telecommunication system. The results show that the error rate of measurement of
      the heart rate is within 2%, which is comparable with that of the traditional
      wired measurement method. The sensitivity of the agility index, which could be
      distinguished as the activity speed, changed slightly. Thus, we confirmed that
      the developed algorithm could be used in an effective and safe exercise
      evaluation system for athletes.

PMID- 29039762
TI  - Marine-Derived 2-Aminoimidazolone Alkaloids. Leucettamine B-Related
      Polyandrocarpamines Inhibit Mammalian and Protozoan DYRK & CLK Kinases.
AB  - A large diversity of 2-aminoimidazolone alkaloids is produced by various marine
      invertebrates, especially by the marine Calcareous sponges Leucetta and
      Clathrina. The phylogeny of these sponges and the wide scope of 2
      aminoimidazolone alkaloids they produce are reviewed in this article. The origin
      (invertebrate cells, associated microorganisms, or filtered plankton),
      physiological functions, and natural molecular targets of these alkaloids are
      largely unknown. Following the identification of leucettamine B as an inhibitor
      of selected protein kinases, we synthesized a family of analogues, collectively
      named leucettines, as potent inhibitors of DYRKs (dual-specificity, tyrosine
      phosphorylation regulated kinases) and CLKs (cdc2-like kinases) and potential
      pharmacological leads for the treatment of several diseases, including
      Alzheimer's disease and Down syndrome. We assembled a small library of marine
      sponge- and ascidian-derived 2-aminoimidazolone alkaloids, along with several
      synthetic analogues, and tested them on a panel of mammalian and protozoan
      kinases. Polyandrocarpamines A and B were found to be potent and selective
      inhibitors of DYRKs and CLKs. They inhibited cyclin D1 phosphorylation on a
      DYRK1A phosphosite in cultured cells. 2-Aminoimidazolones thus represent a
      promising chemical scaffold for the design of potential therapeutic drug
      candidates acting as specific inhibitors of disease-relevant kinases, and
      possibly other disease-relevant targets.

PMID- 29039764
TI  - Human Chorionic Gonadotropin as a Pivotal Endocrine Immune Regulator Initiating
      and Preserving Fetal Tolerance.
AB  - The pregnancy hormone, human chorionic gonadotropin (hCG), is crucially involved
      in processes such as implantation and placentation, two milestones of pregnancy
      whose successful progress is a prerequisite for adequate fetal growth. Moreover,
      hCG determines fetal fate by regulating maternal innate and adaptive immune
      responses allowing the acceptance of the foreign fetal antigens. As one of the
      first signals provided by the embryo to its mother, hCG has the potential to
      regulate very early pregnancy-driven immune responses, allowing the establishment
      and preservation of fetal tolerance. This mini review focuses on how hCG
      modulates the adaptive arm of the immune system including dendritic cells as key
      regulators of adaptive immune responses.

PMID- 29039765
TI  - MEMS Tunable Diffraction Grating for Spaceborne Imaging Spectroscopic
      Applications.
AB  - Diffraction gratings are among the most commonly used optical elements in
      applications ranging from spectroscopy and metrology to lasers. Numerous methods
      have been adopted for the fabrication of gratings, including
      microelectromechanical system (MEMS) fabrication which is by now mature and
      presents opportunities for tunable gratings through inclusion of an actuation
      mechanism. We have designed, modeled, fabricated and tested a silicon based pitch
      tunable diffraction grating (PTG) with relatively large resolving power that
      could be deployed in a spaceborne imaging spectrometer, for example in a
      picosatellite. We have carried out a detailed analytical modeling of PTG, based
      on a mass spring system. The device has an effective fill factor of 52% and
      resolving power of 84. Tuning provided by electrostatic actuation results in a
      displacement of 2.7 MU m at 40 V . Further, we have carried out vibration testing
      of the fabricated structure to evaluate its feasibility for spaceborne
      instruments.

PMID- 29039766
TI  - Identification and Characterization of TALE Homeobox Genes in the Endangered Fern
      Vandenboschia speciosa.
AB  - We report and discuss the results of a quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) analysis of the expression patterns of seven
      three amino acid loop extension (TALE) homeobox genes (four KNOTTED-like homeobox
      (KNOX) and three BEL1-like homeobox (BELL) genes) identified after next
      generation sequencing (NGS) and assembly of the sporophyte and gametophyte
      transcriptomes of the endangered fern species Vandenboschia speciosa. Among the
      four KNOX genes, two belonged to the KNOX1 class and the other two belonged to
      the KNOX2 class. Analysis of the deduced amino acid sequences supported the
      typical domain structure of both types of TALE proteins, and the homology to TALE
      proteins of mosses, lycophytes, and seed plant species. The expression analyses
      demonstrate that these homeodomain proteins appear to have a key role in the
      establishment and development of the gametophyte and sporophyte phases of V.
      speciosa lifecycle, as well as in the control of the transition between both
      phases. Vandenboschia speciosa VsKNAT3 (a KNOX2 class protein) as well as VsBELL4
      and VsBELL10 proteins have higher expression levels during the sporophyte
      program. On the contrary, one V. speciosa KNOX1 protein (VsKNAT6) and one KNOX2
      protein (VsKNAT4) seem important during the development of the gametophyte phase.
      TALE homeobox genes might be among the key regulators in the gametophyte-to
      sporophyte developmental transition in regular populations that show alternation
      of generations, since some of the genes analyzed here (VsKNAT3, VsKNAT6, VsBELL4,
      and VsBELL6) are upregulated in a non-alternating population in which only
      independent gametophytes are found (they grow by vegetative reproduction outside
      of the range of sporophyte distribution). Thus, these four genes might trigger
      the vegetative propagation of the gametophyte and the repression of the sexual
      development in populations composed of independent gametophytes. This study
      represents a comprehensive identification and characterization of TALE homeobox
      genes in V. speciosa, and gives novel insights about the role of these genes in
      fern development.

PMID- 29039767
TI  - Trends and Weekly Cycles in a Large Swiss Emergency Centre: A 10 Year Period at
      the University Hospital of Bern.
AB  - Popular demand for high quality care has increased in recent years. This is also
      the case for medical services and support at all times of the day and night is
      nowadays required. During the last ten years, there has been a marked increase in
      the demands on hospital emergency hospitals, particularly in the Western
      industrialized countries. The present retrospective study investigates how the
      demands on a large Swiss university centre have changed over a period of 10
      years. Patient numbers are differentiated by age, gender, nationality, weekday
      and mode of referral. A retrospective analysis was performed of the data of the
      patients admitted to the Emergency Centre of Bern University Medical Hospital
      (Inselspital) during the ten-year period from 2004 up to and including 2013 and
      who were treated as emergencies. A total of 264,272 patients were included in the
      study. It was shown that there was an uninterrupted annual increase from 23,555
      patients in 2004 to 34,918 patients in 2013 (+48%). Most patients came to the
      Emergency Centre on Mondays, followed by Fridays. Because of the marked increase
      in life expectancy and the resulting demographic changes, there has been a marked
      increase in the number of older patients coming to the Emergency Centre for acute
      medical care. It was found that there were disproportionately high numbers of
      patients aged 20 to 49 years who were not Swiss citizens. In contrast, most
      patients over 60 were Swiss. In the coming years, emergency centres will have to
      adapt to the continued increase in patient numbers. This trend will continue, so
      that it is essential to consider the sociodemographic structure of a region when
      planning the availability of emergency medical care.

PMID- 29039768
TI  - New Cassane Diterpenoids from Caesalpinia sappan and their Antiplasmodial
      Activity.
AB  - One new cassane diterpene possessing an unusual N bridge between C-19 and C-20
      named caesalsappanin R (1), as well as another new diterpene caesalsappanin S
      (2), were isolated from the seeds of Caesalpinia sappanwith methanol extract.
      Their structures were determined by spectroscopic analysis and examined alongside
      existing data from prior studies. Their biological activities were profiled by
      their antiplasmodial activity.

PMID- 29039770
TI  - Alternative Opportunistic Alert Diffusion to Support Infrastructure Failure
      during Disasters.
AB  - Opportunistic communications present a promising solution for disaster network
      recovery in emergency situations such as hurricanes, earthquakes, and floods,
      where infrastructure might be destroyed. Some recent works in the literature have
      proposed opportunistic-based disaster recovery solutions, but they have omitted
      the consideration of mobile devices that come with different network technologies
      and various initial energy levels. This work presents COPE, an energy-aware
      Cooperative OPportunistic alErt diffusion scheme for trapped survivors to use
      during disaster scenarios to report their position and ease their rescue
      operation. It aims to maintain mobile devices functional for as long as possible
      for maximum network coverage until reaching proximate rescuers. COPE deals with
      mobile devices that come with an assortment of networks and aims to perform
      systematic network interface selection. Furthermore, it considers mobile devices
      with various energy levels and allows low-energy nodes to hold their charge for
      longer time with the support of high-energy nodes. A proof-of-concept
      implementation has been performed to study the doability and efficiency of COPE,
      and to highlight the lessons learned.

PMID- 29039769
TI  - "Their Packaging Has Always Been Like a Power": A Qualitative Study of U.S.
      Smokers' Perceptions of Cigarette Pack Visual Design Features to Inform Product
      Regulation.
AB  - Cigarette packaging matters to consumer behavior. However, it is less clear which
      changes to packaging design would be salient for adult smokers. Such information
      is critically important to regulators in the United States who are charged with
      reviewing new tobacco products for their impact on population health. In this
      qualitative study, U.S. adult smokers (n = 33) participated in six telephone
      based focus groups in March 2017. Separate groups were comprised of lesbian, gay,
      and bisexual (LGB) participants; participants with less than four years of post
      secondary education; a mix of LGB and straight participants; and, the general
      population. All groups were purposely selected for diversity. Open thematic
      coding identified salient design elements used on cigarette packaging. Smokers
      articulated design elements' use, meaning, and links with consumer behaviors.
      Three themes were identified: (1) the power of color, (2) supporting color with
      other design elements (e.g., logos/images, typography, the pack itself), and (3)
      the combined product brand experience of multiple design elements. Participants
      linked design elements to product characteristics and to consumer behavior (e.g.,
      purchase). As the Food and Drug Administration is charged with regulating tobacco
      products, these findings suggest the importance of considering the cigarette pack
      part of the characteristics of a product.

PMID- 29039771
TI  - Integrated Process Modeling-A Process Validation Life Cycle Companion.
AB  - During the regulatory requested process validation of pharmaceutical
      manufacturing processes, companies aim to identify, control, and continuously
      monitor process variation and its impact on critical quality attributes (CQAs) of
      the final product. It is difficult to directly connect the impact of single
      process parameters (PPs) to final product CQAs, especially in biopharmaceutical
      process development and production, where multiple unit operations are stacked
      together and interact with each other. Therefore, we want to present the
      application of Monte Carlo (MC) simulation using an integrated process model
      (IPM) that enables estimation of process capability even in early stages of
      process validation. Once the IPM is established, its capability in risk and
      criticality assessment is furthermore demonstrated. IPMs can be used to enable
      holistic production control strategies that take interactions of process
      parameters of multiple unit operations into account. Moreover, IPMs can be
      trained with development data, refined with qualification runs, and maintained
      with routine manufacturing data which underlines the lifecycle concept. These
      applications will be shown by means of a process characterization study recently
      conducted at a world-leading contract manufacturing organization (CMO). The new
      IPM methodology therefore allows anticipation of out of specification (OOS)
      events, identify critical process parameters, and take risk-based decisions on
      counteractions that increase process robustness and decrease the likelihood of
      OOS events.

PMID- 29039772
TI  - Influence of Time-Pickoff Circuit Parameters on LiDAR Range Precision.
AB  - A pulsed time-of-flight (TOF) measurement-based Light Detection and Ranging
      (LiDAR) system is more effective for medium-long range distances. As a key
      ranging unit, a time-pickoff circuit based on automatic gain control (AGC) and
      constant fraction discriminator (CFD) is designed to reduce the walk error and
      the timing jitter for obtaining the accurate time interval. Compared with Cramer
      Rao lower bound (CRLB) and the estimation of the timing jitter, four parameters
      based Monte Carlo simulations are established to show how the range precision is
      influenced by the parameters, including pulse amplitude, pulse width, attenuation
      fraction and delay time of the CFD. Experiments were carried out to verify the
      relationship between the range precision and three of the parameters, exclusing
      pulse width. It can be concluded that two parameters of the ranging circuit
      (attenuation fraction and delay time) were selected according to the ranging
      performance of the minimum pulse amplitude. The attenuation fraction should be
      selected in the range from 0.2 to 0.6 to achieve high range precision. The
      selection criterion of the time-pickoff circuit parameters is helpful for the
      ranging circuit design of TOF LiDAR system.

PMID- 29039773
TI  - A Review of Statistical Failure Time Models with Application of a Discrete Hazard
      Based Model to 1Cr1Mo-0.25V Steel for Turbine Rotors and Shafts.
AB  - Producing predictions of the probabilistic risks of operating materials for given
      lengths of time at stated operating conditions requires the assimilation of
      existing deterministic creep life prediction models (that only predict the
      average failure time) with statistical models that capture the random component
      of creep. To date, these approaches have rarely been combined to achieve this
      objective. The first half of this paper therefore provides a summary review of
      some statistical models to help bridge the gap between these two approaches. The
      second half of the paper illustrates one possible assimilation using 1Cr1Mo-0.25V
      steel. The Wilshire equation for creep life prediction is integrated into a
      discrete hazard based statistical model-the former being chosen because of its
      novelty and proven capability in accurately predicting average failure times and
      the latter being chosen because of its flexibility in modelling the failure time
      distribution. Using this model it was found that, for example, if this material
      had been in operation for around 15 years at 823 K and 130 MPa, the chances of
      failure in the next year is around 35%. However, if this material had been in
      operation for around 25 years, the chance of failure in the next year rises
      dramatically to around 80%.

PMID- 29039774
TI  - Transnational Dynamics Amid Poor Regulations: Taiwan's Asbestos Ban Actions and
      Experiences.
AB  - This article describes the history of the asbestos use regulation process in
      Taiwan and the associated factors leading to its total ban in 2018. Despite the
      long history of asbestos mining and manufacturing since the Japanese colonial
      period, attempts to understand the impact of asbestos on the health of the
      population and to control its use did not emerge until the early 1980s. We
      attempted to investigate the driving forces and obstructions involved in asbestos
      regulations by reviewing available public sources and scientific journal articles
      and conducting interviews with key propagators of the asbestos regulation and
      ban. Correlation between asbestos exposure and asbestos-related diseases has
      already been established; however, authorities have been unable to effectively
      regulate the extensive application of asbestos in various light industries that
      support economic growth since the 1960s. More stringent regulations on asbestos
      use in industries and an eventual ban were caused indirectly by appeals made by
      visionary scholars and healthcare professionals but also due to the subsidence of
      asbestos-related industries. With the elucidation of factors that affect asbestos
      regulation and ban, a thorough long-term healthcare plan for the neglected
      victims of asbestos-related diseases and upstream measures for policy change must
      be developed.

PMID- 29039775
TI  - Physiological and Perceptual Responses to Nordic Walking in a Natural Mountain
      Environment.
AB  - Background: Interest around Nordic Walking (NW) has increased in recent years.
      However, direct comparisons of NW with normal walking (W), particularly in
      ecologically valid environments is lacking. The aim of our study was to compare
      NW and W, over long distances in a natural mountain environment. Methods: Twenty
      one subjects (13 male/8 female, aged 41 +/- 12 years, body mass index BMI 24.1 +/
      3.7), walked three distinct uphill paths (length 2.2/3.4/7 km) with (NW) or
      without (W) walking poles over two separate days. Heart rate (HR), energy
      expenditure (EE), step length (SL), walking speed (WS), total steps number (SN)
      and rating of perceived exertion (RPE) were monitored. Results: HR (+18%) and EE
      (+20%) were higher in NW than in W whilst RPE was similar. SN (-12%) was lower
      and SL (+15%) longer in NW. WS was higher (1.64 vs. 1.53 m s-1) in NW.
      Conclusions: Our data confirm that, similarly to previous laboratory studies,
      differences in a range of walking variables are present between NW and W when
      performed in a natural environment. NW appears to increase EE compared to W,
      despite a similar RPE. Thus, NW could be a useful as aerobic training modality
      for weight control and cardiorespiratory fitness.

PMID- 29039776
TI  - Roles of Aryl Hydrocarbon Receptor in Aromatase-Dependent Cell Proliferation in
      Human Osteoblasts.
AB  - Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and
      its expression is influenced by environmental compounds, such as 3
      methylcholanthrene (3-MC) and beta-naphthoflavone (beta-NF). AhR and its
      downstream genes, such as CYP1A1, are considered to play a pivotal role in
      xenobiotic responses. AhR signaling has also been proposed to mediate
      osteogenesis in experimental animals, but its details have remained unclear.
      Therefore, in this study, we examined the possible roles of AhR in human bone.
      Immunohistochemical analysis revealed that AhR was detected in both osteoblasts
      and osteoclasts. We then screened AhR-target genes using a microarray analysis in
      human osteoblastic hFOB cells. Results of microarray and subsequent PCR analysis
      did reveal that estrogen metabolizing and synthesizing enzymes, such as CYP1B1
      and aromatase, were increased by 3-MC in hFOB and osteosarcoma cell line, MG-63.
      The subsequent antibody cytokine analysis also demonstrated that interleukin
      1beta and -6 expression was increased by 3-MC and beta-NF in hFOB cells and these
      interleukins were well known to induce aromatase. We then examined the cell
      proliferation rate of hFOB and MG-63 cells co-treated with 3-MC and testosterone
      as an aromatase substrate. The status of cell proliferation in both hFOB and MG
      63 cells was stimulated by 3-MC and testosterone treatment, which was also
      inhibited by an estrogen blocker, aromatase inhibitor, or AhR antagonist. These
      findings indicated that AhR could regulate estrogen synthesis and metabolism in
      bone tissues through cytokine/aromatase signaling.

PMID- 29039777
TI  - The Specific Mitogen- and Stress-Activated Protein Kinase MSK1 Inhibitor SB
      747651A Modulates Chemokine-Induced Neutrophil Recruitment.
AB  - Mitogen-activated protein kinase (MAPK) signaling is involved in a variety of
      cellular functions. MAPK-dependent functions rely on phosphorylation of target
      proteins such as mitogen- and stress-activated protein kinase 1 (MSK1). MSK1
      participates in the early gene expression and in the production of pro- and anti
      inflammatory cytokines. However, the role of MSK1 in neutrophil recruitment
      remains elusive. Here, we show that chemokine macrophage inflammatory protein-2
      (CXCL2) enhances neutrophil MSK1 expression. Using intravital microscopy and time
      lapsed video analysis of cremasteric microvasculature in mice, we studied the
      effect of pharmacological suppression of MSK1 by SB-747651A on CXCL2-elicited
      neutrophil recruitment. SB-747651A treatment enhanced CXCL2-induced neutrophil
      adhesion while temporally attenuating neutrophil emigration. CXCL2-induced
      intraluminal crawling was reduced following SB-747651A treatment. Fluorescence
      activated cell sorting analysis of integrin expression revealed that SB-747651A
      treatment attenuated neutrophil integrin alphaMbeta2 (Mac-1) expression following
      CXCL2 stimulation. Both the transmigration time and detachment time of
      neutrophils from the venule were increased following SB-747651A treatment. It
      also decreased the velocity of neutrophil migration in cremasteric tissue in
      CXCL2 chemotactic gradient. SB-747651A treatment enhanced the extravasation of
      neutrophils in mouse peritoneal cavity not at 1-2 h but at 3-4 h following CXCL2
      stimulation. Collectively, our data suggest that inhibition of MSK1 by SB-747651A
      treatment affects CXCL2-induced neutrophil recruitment by modulating various
      steps of the recruitment cascade in vivo.

PMID- 29039778
TI  - Comparison of Two Sources of Clinical Audit Data to Assess the Delivery of
      Diabetes Care in Aboriginal Communities.
AB  - The objective of this study was to determine the concordance between data
      extracted from two Clinical Decision Support Systems regarding diabetes testing
      and monitoring at Aboriginal Community Controlled Health Services in Australia.
      De-identified PenCAT and Communicare Systems data were extracted from the
      services allocated to the intervention arm of a diabetes care trial, and intra
      class correlations for each extracted item were derived at a service level.
      Strong to very strong correlations between the two data sources were found
      regarding the total number of patients with diabetes per service (Intra-class
      correlation [ICC] = 0.99), as well as the number (ICC = 0.98-0.99) and proportion
      (ICC = 0.96) of patients with diabetes by gender. The correlation was moderate
      for the number and proportion of Type 2 diabetes patients per service in the
      group aged 18-34 years (ICC = 0.65 and 0.8-0.82 respectively). Strong to very
      strong correlations were found for numbers and proportions of patients being
      tested for diabetes, and for appropriate monitoring of patients known to have
      diabetes (ICC = 0.998-1.00). This indicated a generally high degree of
      concordance between whole-service data extracted by the two Clinical Decision
      Support Systems. Therefore, the less expensive or less complex option (depending
      on the individual circumstances of the service) may be appropriate for monitoring
      diabetes testing and care. However, the extraction of data about subgroups of
      patients may not be interchangeable.

PMID- 29039779
TI  - Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and
      Biological Evaluation.
AB  - Continuing our structure-activity studies on the vitamin D analogs with the
      altered intercyclic seco-B-ring fragment, we designed compounds possessing
      dienyne system conjugated with the benzene D ring. Analysis of the literature
      data and the docking experiments seemed to indicate that the target compounds
      could mimic the ligands with a good affinity to the vitamin D receptor (VDR).
      Multi-step synthesis of the C/D-ring building block of the tetralone structure
      was achieved and its enol triflate was coupled with the known A-ring fragments,
      possessing conjugated enyne moiety, using Sonogashira protocol. The structures of
      the final products were confirmed by NMR, UV and mass spectroscopy. Their binding
      affinities for the full-length human VDR were determined and it was established
      that compound substituted at C-2 with exomethylene group showed significant
      binding to the receptor. This analog was also able to induce monocytic
      differentiation of HL-60 cells.

PMID- 29039780
TI  - Housing and Health of Kiribati Migrants Living in New Zealand.
AB  - Settlement is a complex process of adjustment for migrants and refugees. Drawing
      on recent research on the settlement experiences of Kiribati migrants and their
      families living in New Zealand, this article examines the role of housing as an
      influencer of the settlement and health of Kiribati migrants. Using qualitative
      methodology, in-depth interviews were conducted with fourteen Kiribati migrants
      (eight women and six men) representing 91 family members about the key issues and
      events that shaped their settlement in New Zealand. The stories told by
      participants affirm the association between housing and health. The study serves
      as an important reminder that children bear a great cost from living in poorly
      insulated and damp housing, and adults bear the mental costs, including social
      isolation resulting from inadequate rental housing. Detailed information about
      how this migrant group entered the private rental housing market, by taking over
      the rental leases of other Kiribati migrants vacating their rental properties,
      indicated some of the unintended consequences related to a lack of incentives for
      landlords to make improvements. With the most vulnerable families most at risk
      from inadequate housing, this research concludes that there is a need for minimum
      housing standards to protect tenants.

PMID- 29039781
TI  - China's Insurance Regulatory Reform, Corporate Governance Behavior and Insurers'
      Governance Effectiveness.
AB  - External regulation is an important mechanism to improve corporate behavior in
      emerging markets. China's insurance governance regulation, which began to
      supervise and guide insurance corporate governance behavior in 2006, has
      experienced a complex process of reform. This study tested our hypotheses with a
      sample of 85 firms during 2010-2011, which was obtained by providing a
      questionnaire to all of China's shareholding insurance companies. The empirical
      study results generally show that China's insurance governance effectiveness has
      significantly improved through strict regulation. Insurance corporate governance
      can improve business acumen and risk-control ability, but no significant evidence
      was found to prove its influence on profitability, as a result of focusing less
      attention on governance than on management. State ownership is associated with
      higher corporate governance effectiveness than non-state ownership. Listed
      companies tend to outperform non-listed firms, and life insurance corporate
      governance is more effective than that of property insurers. This study not only
      contributes to the comprehensive understanding of corporate governance
      effectiveness but also to the literature by highlighting the effect of corporate
      governance regulation in China's insurance industry and other emerging economies
      of the financial sector.

PMID- 29039782
TI  - Antibacterial and Tribological Performance of Carbonitride Coatings Doped with W,
      Ti, Zr, or Cr Deposited on AISI 316L Stainless Steel.
AB  - Carbonitride (CNx) coatings have existed for several decades but are not well
      understood. Related studies have indicated that CNx coatings exhibit behaviors
      comparable to diamond-like carbon (DLC) coatings. Metal-doped CNx coatings are
      expected to show superior performance to single CNx coatings. In this study, a
      CNx coating and a group of CNx coatings with 6 at. % metal doping (W, Ti, Zr, or
      Cr) were prepared on biograde AISI 316L stainless steel (SS316L) substrates, and
      they were then characterized and studied for antibacterial and wear performance.
      The microstructure, constituent phase, nanohardness, adhesion, surface roughness,
      and contact angle were evaluated. The antimicrobial test used Staphylococcus
      aureus and followed the Japanese Industrial Standard JIS Z 2801:2010. Finally,
      the wear behavior was assessed. The results showed that the CNx coating was a
      composite of amorphous CNx and amorphous C structures. The metal doping caused
      crystalline metal carbides/nitrides to form in the CNx coatings, which weakened
      their overall integrity. All the coatings showed antimicrobial ability for the
      SS316L samples. The CNx-Zr coating, the surface of which had the highest
      hydrophilicity, produced the best antibacterial performance. However, the CNx-Zr
      coating showed lower wear resistance than the CNx-W and CNx-Ti coatings. The CNx
      Ti coating with a highly hydrophilic surface exhibited the lowest antibacterial
      ability.

PMID- 29039783
TI  - Quantitative Phosphoproteomic Analysis Provides Insight into the Response to
      Short-Term Drought Stress in Ammopiptanthus mongolicus Roots.
AB  - Drought is one of the major abiotic stresses that negatively affects plant growth
      and development. Ammopiptanthus mongolicus is an ecologically important shrub in
      the mid-Asia desert region and used as a model for abiotic tolerance research in
      trees. Protein phosphorylation participates in the regulation of various
      biological processes, however, phosphorylation events associated with drought
      stress signaling and response in plants is still limited. Here, we conducted a
      quantitative phosphoproteomic analysis of the response of A. mongolicus roots to
      short-term drought stress. Data are available via the iProx database with project
      ID IPX0000971000. In total, 7841 phosphorylation sites were found from the 2019
      identified phosphopeptides, corresponding to 1060 phosphoproteins. Drought stress
      results in significant changes in the abundance of 103 phosphopeptides,
      corresponding to 90 differentially-phosphorylated phosphoproteins (DPPs). Motif-x
      analysis identified two motifs, including [pSP] and [RXXpS], from these DPPs.
      Functional enrichment and protein-protein interaction analysis showed that the
      DPPs were mainly involved in signal transduction and transcriptional regulation,
      osmotic adjustment, stress response and defense, RNA splicing and transport,
      protein synthesis, folding and degradation, and epigenetic regulation. These
      drought-corresponsive phosphoproteins, and the related signaling and metabolic
      pathways probably play important roles in drought stress signaling and response
      in A. mongolicus roots. Our results provide new information for understanding the
      molecular mechanism of the abiotic stress response in plants at the
      posttranslational level.

PMID- 29039784
TI  - Crosstalk Influence between P38MAPK and Autophagy on Mitochondria-Mediated
      Apoptosis Induced by Anti-Fas Antibody/Actinomycin D in Human Hepatoma Bel-7402
      Cells.
AB  - Our previous study indicated that anti-Fas antibody/actinomycin D (AF/AD) induced
      apoptosis of human hepatocellular carcinoma Bel-7402 cells; however, crosstalk
      influence between P38MAPK and autophagy on mitochondria-mediated apoptosis
      induced by AF/AD in Bel-7402 cells remains unclear. Therefore, effect of AF/AD on
      apoptosis, autophagy, phosphorylated-P38MAPK (p-P38MAPK), and membrane potential
      (DeltaPsim) with or without the P38MAPK inhibitor SB203580 or the autophagy
      inhibitor 3-methyladenine (3-MA) in Bel-7402 cells was investigated in the
      present study. The results showed that AF/AD resulted in induction of apoptosis
      concomitant with autophagy, upregulation of p-P38MAPK and autophagy-associated
      gene proteins (Atg5-Atg12 protein complex, Atg7, Atg10, Beclin-1, LC3 I, and LC3
      II), and downregulation of DeltaPsim in Bel-7402 cells. In contrast, SB203580
      attenuated the effects of AF/AD in Bel-7402 cells. Furthermore, the findings also
      demonstrated that 3-MA inhibited the impact of AF/AD on autophagy, Atg5-Atg12
      protein complex, Atg7, Atg10, Beclin-1, LC3 I, LC3 II, and DeltaPsim, and
      promoted the influence of AF/AD on apoptosis and p-P38MAPK in Bel-7402 cells.
      Taken together, we conclude that crosstalk between P38MAPK and autophagy
      regulates mitochondria-mediated apoptosis induced by AF/AD in Bel-7402 cells.

PMID- 29039785
TI  - Prospective Comparison of F-18 Choline PET/CT Scan Versus Axial MRI for Detecting
      Bone Metastasis in Biochemically Relapsed Prostate Cancer Patients.
AB  - We compared fluor-18 choline positron emission tomography/computed tomography
      (PET/CT) and axial skeleton magnetic resonance imaging (MRI) prospectively
      obtained for the detection of bone metastases in non-castrated patients with
      biochemically recurrent prostate cancer following primary treatment. PET/CT was
      performed 45 min post-injection of 3-4 MBq/kg F-18 methyl choline. MRI included
      T1- and fluid sensitive T2-weighted images of the spine and pelvis. Readers were
      initially blinded from other results and all scans underwent independent double
      reading. The best valuable comparator (BVC) defined the metastatic status. On the
      basis of the BVC, 15 out of 64 patients presented with 24 bone metastases. On a
      patient level, the sensitivity and specificity of MRI and PET were not
      significantly different. On a lesion level, the sensitivity of MRI was
      significantly better compared to PET, and the specificity did not differ
      significantly. In conclusion, axial MRI is an interesting screening tool for the
      detection of bone metastases because of its low probability of false negative
      results. However, F-18 choline PET is a valuable addition as it can overrule
      false positive MRI results and detect non-axial metastases.

PMID- 29039787
TI  - Cold Treatment Induces Transient Mitochondrial Fragmentation in Arabidopsis
      thaliana in a Way that Requires DRP3A but not ELM1 or an ELM1-Like Homologue,
      ELM2.
AB  - The number, size and shape of polymorphic plant mitochondria are determined at
      least partially by mitochondrial fission. Arabidopsis mitochondria divide through
      the actions of a dynamin-related protein, DRP3A. Another plant-specific factor,
      ELM1, was previously shown to localize DRP3A to mitochondrial fission sites.
      Here, we report that mitochondrial fission is not completely blocked in the
      Arabidopsis elm1 mutant and that it is strongly manifested in response to cold
      treatment. Arabidopsis has an ELM1 paralogue (ELM2) that seems to have only a
      limited role in mitochondrial fission in the elm1 mutant. Interestingly, cold
      induced mitochondrial fragmentation was also observed in the wild-type, but not
      in a drp3a mutant, suggesting that cold-induced transient mitochondrial
      fragmentation requires DRP3A but not ELM1 or ELM2. DRP3A: GFP localized from the
      cytosol to mitochondrial fission sites without ELM1 after cold treatment.
      Together, these results suggest that Arabidopsis has a novel, cold-induced type
      of mitochondrial fission in which DRP3A localizes to mitochondrial fission sites
      without the involvement of ELM1 or ELM2.

PMID- 29039786
TI  - TGF-beta-Induced Endothelial-Mesenchymal Transition in Fibrotic Diseases.
AB  - Fibrotic diseases are characterized by net accumulation of extracellular matrix
      proteins in affected organs leading to their dysfunction and ultimate failure.
      Myofibroblasts have been identified as the cells responsible for the progression
      of the fibrotic process, and they originate from several sources, including
      quiescent tissue fibroblasts, circulating CD34+ fibrocytes and the phenotypic
      conversion of various cell types into activated myofibroblasts. Several studies
      have demonstrated that endothelial cells can transdifferentiate into mesenchymal
      cells through a process termed endothelial- mesenchymal transition (EndMT) and
      that this can give rise to activated myofibroblasts involved in the development
      of fibrotic diseases. Transforming growth factor beta (TGF-beta) has a central
      role in fibrogenesis by modulating the fibroblast phenotype and function,
      inducing myofibroblast transdifferentiation and promoting matrix accumulation. In
      addition, TGF-beta by inducing EndMT may further contribute to the development of
      fibrosis. Despite extensive investigation of the pathogenesis of fibrotic
      diseases, no effective treatment strategies are available. Delineation of the
      mechanisms responsible for initiation and progression of fibrotic diseases is
      crucial for the development of therapeutic strategies for the treatment of the
      disease. In this review, we summarize the role of the TGF-beta signaling pathway
      and EndMT in the development of fibrotic diseases and discuss their therapeutic
      potential.

PMID- 29039789
TI  - Electrospun Phospholipid Fibers as Micro-Encapsulation and Antioxidant Matrices.
AB  - Electrospun phospholipid (asolectin) microfibers were investigated as
      antioxidants and encapsulation matrices for curcumin and vanillin. These
      phospholipid microfibers exhibited antioxidant properties which increased after
      the encapsulation of both curcumin and vanillin. The total antioxidant capacity
      (TAC) and the total phenolic content (TPC) of curcumin/phospholipid and
      vanillin/phospholipid microfibers remained stable over time at different
      temperatures (refrigerated, ambient) and pressures (vacuum, ambient). 1H-NMR
      confirmed the chemical stability of both encapsulated curcumin and vanillin
      within phospholipid fibers. Release studies in aqueous media revealed that the
      phenolic bioactives were released mainly due to swelling of the phospholipid
      fiber matrix over time. The above studies confirm the efficacy of electrospun
      phospholipid microfibers as encapsulation and antioxidant systems.

PMID- 29039788
TI  - Impact of Natural Compounds on DNA Methylation Levels of the Tumor Suppressor
      Gene RASSF1A in Cancer.
AB  - Epigenetic inactivation of tumor suppressor genes (TSG) is a fundamental event in
      the pathogenesis of human cancer. This silencing is accomplished by aberrant
      chromatin modifications including DNA hypermethylation of the gene promoter. One
      of the most frequently hypermethylated TSG in human cancer is the Ras Association
      Domain Family 1A (RASSF1A) gene. Aberrant methylation of RASSF1A has been
      reported in melanoma, sarcoma and carcinoma of different tissues. RASSF1A
      hypermethylation has been correlated with tumor progression and poor prognosis.
      Reactivation of epigenetically silenced TSG has been suggested as a therapy in
      cancer treatment. In particular, natural compounds isolated from herbal extracts
      have been tested for their capacity to induce RASSF1A in cancer cells, through
      demethylation. Here, we review the treatment of cancer cells with natural
      supplements (e.g., methyl donors, vitamins and polyphenols) that have been
      utilized to revert or prevent the epigenetic silencing of RASSF1A. Moreover, we
      specify pathways that were involved in RASSF1A reactivation. Several of these
      compounds (e.g., reseveratol and curcumin) act by inhibiting the activity or
      expression of DNA methyltransferases and reactive RASSF1A in cancer. Thus natural
      compounds could serve as important agents in tumor prevention or cancer therapy.
      However, the exact epigenetic reactivation mechanism is still under
      investigation.

PMID- 29039790
TI  - ProLanGO: Protein Function Prediction Using Neural Machine Translation Based on a
      Recurrent Neural Network.
AB  - With the development of next generation sequencing techniques, it is fast and
      cheap to determine protein sequences but relatively slow and expensive to extract
      useful information from protein sequences because of limitations of traditional
      biological experimental techniques. Protein function prediction has been a long
      standing challenge to fill the gap between the huge amount of protein sequences
      and the known function. In this paper, we propose a novel method to convert the
      protein function problem into a language translation problem by the new proposed
      protein sequence language "ProLan" to the protein function language "GOLan", and
      build a neural machine translation model based on recurrent neural networks to
      translate "ProLan" language to "GOLan" language. We blindly tested our method by
      attending the latest third Critical Assessment of Function Annotation (CAFA 3) in
      2016, and also evaluate the performance of our methods on selected proteins whose
      function was released after CAFA competition. The good performance on the
      training and testing datasets demonstrates that our new proposed method is a
      promising direction for protein function prediction. In summary, we first time
      propose a method which converts the protein function prediction problem to a
      language translation problem and applies a neural machine translation model for
      protein function prediction.

PMID- 29039791
TI  - Synthesis of Chiral TFA-Protected alpha-Amino Aryl-Ketone Derivatives with
      Friedel-Crafts Acylation of alpha-Amino Acid N-Hydroxysuccinimide Ester.
AB  - Chiral N-protected alpha-amino aryl-ketones are one of the useful precursors used
      in the synthesis of various biologically active compounds and can be constructed
      via Friedel-Crafts acylation of N-protected alpha-amino acids. One of the
      drawbacks of this reaction is the utilization of toxic, corrosive and moisture
      sensitive acylating reagents. In peptide construction via amide bond formation, N
      hydroxysuccinimide ester (OSu), which has high storage stability, can react
      rapidly with amino components and produces fewer side reactions, including
      racemization. This study reports the first synthesis and utilization of N
      trifluoroacetyl (TFA)-protected alpha-amino acid-OSu as a potential acyl donor
      for Friedel-Crafts acylation into various arenes. The TFA-protected isoleucine
      derivative and its diastereomer TFA-protected allo-isoleucine derivative were
      investigated to check the retention of alpha-proton chirality in the Friedel
      Crafts reaction. Further utilization of OSu in other branched-chain and
      unbranched-chain amino acids results in an adequate yield of TFA-protected alpha
      amino aryl-ketone without loss of optical purity.

PMID- 29039792
TI  - Health-Promoting Phytochemicals from 11 Mustard Cultivars at Baby Leaf and Mature
      Stages.
AB  - Mustard is a Brassica vegetable that provides a number of phytonutrients.
      However, the phytonutrient profile of mustard has been relatively limited. We
      analyzed the glucosinolates and their hydrolysis products, carotenoids, total
      anthocyanin and phenolic contents, and antioxidant capacity of the leaves of 11
      mustard cultivars grown in a greenhouse at the baby leaf and mature stages. An
      aliphatic glucosinolate sinigrin and its hydrolysis products allyl isothiocyanate
      and 1-cyano-2,3-epithiopropane were the major phytonutrients in the mustard
      leaves. Carotenoids beta-carotene, lutein, violaxanthin, and neoxanthin were
      detected. We found phytonutrient concentration and their change with plant growth
      were cultivar-dependent. The %RDA value for vitamin A calculated using beta
      carotene content and retinol activity equivalents suggests that mustard cultivars
      used in this study can be a good source of vitamin A. Phenolic contents and
      antioxidant capacity also varied among cultivars and between physiological
      stages. Our results suggest that mustard leaves are rich in various
      phytochemicals and their composition depends on cultivar and the physiological
      stage. This is the first report on phytochemical composition in various mustard
      cultivars at different physiological stages.

PMID- 29039793
TI  - Pharmacokinetic Comparison of Seven Major Bio-Active Components in Normal and
      Blood Stasis Rats after Oral Administration of Herb Pair Danggui-Honghua by UPLC
      TQ/MS.
AB  - The compatibility between Danggui (Angelicae Sinensis Radix) and Honghua
      (Carthami Flos) is a known herb pair, which could activate blood circulation and
      dissipate blood stasis effects. In this paper, we quantified seven main bio
      active components (hydroxysafflor yellow A, caffeic acid, p-coumaric acid,
      kaempferol-3-O-rutinoside, ferulic acid, 3-n-butylphthalide, and ligustilide) in
      plasma samples in vivo by UPLC-TQ/MS method and investigatedwhether the
      pharmacokinetic (PK) behaviors of the seven components could be altered in blood
      stasis rats after oral administration of the Gui-Hong extracts. It was found that
      the Cmax and AUC0-t of these components in blood stasis rats had increasing
      tendency compared with normal rats. Most components in model and normal rats had
      significant difference in some pharmacokinetic parameters, which indicated that
      the metabolism enzymes and transporters involved in the metabolism and
      disposition of these bio-active componentsmay bealtered in blood stasis rats.
      This study was the first report about the pharmacokinetic investigation between
      normal and blood stasis rats after oral administrationof Gui-Hong extracts, and
      these results are important and valuable for better clinical applications of Gui
      Hong herb pair and relatedTCM formulae.

PMID- 29039794
TI  - Heat Shock Protein-Inducing Property of Diarylheptanoid Containing Chalcone
      Moiety from Alpinia katsumadai.
AB  - A new diarylheptanoid containing a chalcone moiety, katsumain H (1), was isolated
      from the seeds of Alpinia katsumadai. The structure was elucidated using a
      combination of 1D/2D NMR spectroscopy and mass spectrometry data analysis. The
      absolute configurations of C-3, C-5, and C-7 in 1 were assigned based on its
      optical rotation and after comparing its NMR chemical shifts with those of its
      diastereoisomers, katsumain E and katsumain F, which were previously isolated
      from this plant and characterized. In this study, the stimulatory effects of
      compounds 1 and 2 were evaluated on heat shock factor 1 (HSF1), heat shock
      protein 27 (HSP27), and HSP70. Compounds 1 and 2 increased the expression of HSF1
      (1.056- and 1.200-fold, respectively), HSP27 (1.312- and 1.242-fold,
      respectively), and HSP70 (1.234- and 1.271-fold, respectively), without increased
      cytotoxicity.

PMID- 29039796
TI  - Development and Validation of the Celiac Disease-Children's Activities Report (CD
      Chart) for Promoting Self-Management among Children and Adolescents.
AB  - Adherence to a restrictive gluten-free diet is the only known treatment for
      celiac disease (CD). Children and adolescents with CD encounter challenges while
      managing the diet in daily activities. Understanding their participation
      characteristics is lacking. The aim was to describe the development and
      validation process of the Celiac Disease-Children's Activities Report (CD-Chart).
      The final CD-Chart includes nine food-related activities that are measured by six
      core dimensions: frequency, preference, preparation, involvement, help, and self
      determination. Participants were 126 children (8-11 years) and adolescents (12-18
      years) with CD, and 30 healthy matched controls. Factor analysis was performed
      and psychometric properties were measured. Content and face validity was
      established and the CD-Chart showed adequate internal consistency as measured by
      the preference dimension (alpha = 0.81). Factor analysis revealed two distinct
      factors, social environment and close family environment. Construct validity
      demonstrated that the group with CD required significantly more pre-preparation
      for food-related activities than controls, (t(38) = 76.25, p < 0.001) and further
      differences as well as similarities were found between groups. Primary results
      indicate that the CD-Chart may serve as a practical tool for acquiring
      information about participation characteristics in food-related activities,
      strengths and challenges of children and adolescents with CD, to promote self
      management, diet adherence, and well-being.

PMID- 29039797
TI  - Dispersions of Goethite Nanorods in Aprotic Polar Solvents.
AB  - Colloidal suspensions of anisotropic nanoparticles can spontaneously self
      organize in liquid-crystalline phases beyond some concentration threshold. These
      phases often respond to electric and magnetic fields. At lower concentrations,
      usual isotropic liquids are observed but they can display very strong Kerr and
      Cotton-Mouton effects (i.e., field-induced particle orientation). For many
      examples of these colloidal suspensions, the solvent is water, which hinders most
      electro-optic applications. Here, for goethite (alpha-FeOOH) nanorod dispersions,
      we show that water can be replaced by polar aprotic solvents, such as N-methyl-2
      pyrrolidone (NMP) and dimethylsulfoxide (DMSO), without loss of colloidal
      stability. By polarized-light microscopy, small-angle X-ray scattering and
      electro-optic measurements, we found that the nematic phase, with its field
      response properties, is retained. Moreover, a strong Kerr effect was also
      observed with isotropic goethite suspensions in these polar aprotic solvents.
      Furthermore, we found no significant difference in the behavior of both the
      nematic and isotropic phases between the aqueous and non-aqueous dispersions. Our
      work shows that goethite nanorod suspensions in polar aprotic solvents, suitable
      for electro-optic applications, can easily be produced and that they keep all
      their outstanding properties. It also suggests that this solvent replacement
      method could be extended to the aqueous colloidal suspensions of other kinds of
      charged anisotropic nanoparticles.

PMID- 29039795
TI  - Milk Intake at Midlife and Cognitive Decline over 20 Years. The Atherosclerosis
      Risk in Communities (ARIC) Study.
AB  - Background: Faster rates of cognitive decline are likely to result in earlier
      onset of cognitive impairment and dementia. d-galactose, a derivative of lactose,
      is used in animal studies to induce neurodegeneration. Milk is the primary source
      of lactose in the human diet, and its effects on cognitive decline have not been
      fully evaluated. Objective: Assess the association of milk intake with change in
      cognitive function over 20 years. Methods: A total of 13,751 participants of the
      Atherosclerosis Risk in Communities (ARIC) cohort completed a food frequency
      questionnaire and three neurocognitive evaluations from 1990 through 2013. Two
      single nucleotide polymorphisms (SNPs) were used to determine lactase persistence
      (LCT-13910 C/T for Whites and LCT-14010 G/C for Blacks). Mixed-effects models
      were used to study the association of milk intake with cognitive change. Multiple
      imputations by chained equations were used to account for attrition. Results:
      Milk intake greater than 1 glass/day was associated with greater decline in the
      global z-score over a 20-year period. The difference in decline was 0.10 (95% CI:
      0.16, 0.03) z-scores, or an additional 10% decline, relative to the group
      reporting "almost never" consuming milk. Conclusions: Replication of these
      results is warranted in diverse populations with greater milk intake and higher
      variability of lactase persistence genotype.

PMID- 29039798
TI  - The Effect of Taurine on the Recovery from Eccentric Exercise-Induced Muscle
      Damage in Males.
AB  - Eccentric exercise is known to bring about microstructural damage to muscle,
      initiating an inflammatory cascade involving various reactive oxygen species.
      This, in turn, can significantly impair physical performance over subsequent
      days. Taurine, a powerful endogenous antioxidant, has previously been shown to
      have a beneficial effect on muscle damage markers and recovery when taken for a
      few days to several weeks prior to eccentric exercise. However, to date no
      studies have looked at the effects of supplementing over the days following
      eccentric exercise on performance recovery. Thus, this study aimed to determine
      whether supplementing with taurine over three days following eccentric exercise
      attenuated the rise in serum creatine kinase and improved performance recovery in
      males. In a blinded, randomized, crossover design, ten recreationally-fit male
      participants completed 60 eccentric contractions of the biceps brachii muscle at
      maximal effort. Following this, participants were supplemented with 0.1 g?kg-1
      body weight?day-1 of either taurine or rice flour in capsules. Over the next
      three mornings participants underwent blood tests for the analysis of the muscle
      damage marker creatine kinase and carried out performance measures on the
      isokinetic dynamometer. They also continued to consume the capsules in the
      morning and evening. The entire protocol was repeated two weeks later on the
      alternate arm and supplement. Significant decreases were seen in all performance
      measures from pre- to 24-h post-eccentric exercise (p < 0.001) for both taurine
      and placebo, indicating the attainment of muscle damage. Significant treatment
      effects were observed only for peak eccentric torque (p < 0.05). No significant
      time * treatment effects were observed (all p > 0.05). Serum creatine kinase
      levels did not significantly differ over time for either treatments, nor between
      treatments (p > 0.05). These findings suggest that taurine supplementation taken
      twice daily for 72 h following eccentric exercise-induced muscle damage may help
      improve eccentric performance recovery of the biceps brachii.

PMID- 29039799
TI  - Solvent-Free Addition of Indole to Aldehydes: Unexpected Synthesis of Novel 1-[1
      (1H-Indol-3-yl) Alkyl]-1H-Indoles and Preliminary Evaluation of Their
      Cytotoxicity in Hepatocarcinoma Cells.
AB  - New 1-[1-(1H-indol-3-yl) alkyl]-1H-indoles, surprisingly, have been obtained from
      the addition of indole to a variety of aldehydes under neat conditions. CaO,
      present in excess, was fundamental for carrying out the reaction with
      paraformaldehyde. Under the same reaction conditions, aromatic and heteroaromatic
      aldehydes afforded only classical bis (indolyl) aryl indoles. In this paper, the
      role of CaO, together with the regiochemistry and the mechanism of the reaction,
      are discussed in detail. The effect of some selected 3,3'- and 1,3'-diindolyl
      methane derivatives on cell proliferation of the hepatoma cell line FaO was also
      evaluated.

PMID- 29039800
TI  - High Ethanol Contents of Spirit Drinks in Kibera Slums, Kenya: Implications for
      Public Health.
AB  - Cheap licit and artisanal illicit spirit drinks have been associated with
      numerous outbreaks of alcohol poisoning especially with methanol. This study
      aimed to evaluate the quality of cheap spirit drinks in Kibera slums in Nairobi
      County, Kenya. The samples consisted of cheap licit spirits (n = 11) and the
      artisanal spirit drink, 'chang'aa', (n = 28). The parameters of alcoholic
      strength and volatile composition were used as indicators of quality and were
      determined using gas chromatography with flame ionization detection (GC-FID) and
      gas chromatography-mass spectrometry (GC-MS) respectively. The ranges for
      alcoholic strength were 42.8-85.8% vol and 28.3-56.7% vol for chang'aa and licit
      spirit drinks respectively, while the pH ranges were 3.3-4.2 and 4.4-4.8 for
      chang'aa and licit spirit drinks respectively. The majority of volatiles were
      found in artisanal spirits and they included higher alcohols, ethyl esters and
      carbonyl compounds. The alcoholic strength of all the artisanal spirits (100%)
      and 91% of the licit spirits was above the 40% vol of standard spirits such as
      vodka. The high ethanol content of the alcohol products was the only element of
      public health significance in this study.

PMID- 29039801
TI  - Stability of Commercially Available Macular Carotenoid Supplements in Oil and
      Powder Formulations.
AB  - We previously identified that the concentration of zeaxanthin in some
      commercially available carotenoid supplements did not agree with the product's
      label claim. The conclusion of this previous work was that more quality assurance
      was needed to guarantee concordance between actual and declared concentrations of
      these nutrients i.e., lutein (L) zeaxanthin (Z) and meso-zeaxanthin (MZ) in
      commercially available supplements. Since this publication, we performed further
      analyses using different commercially available macular carotenoid supplements.
      Three capsules from one batch of eight products were analysed at two different
      time points. The results have been alarming. All of the powder filled products (n
      = 3) analysed failed to comply with their label claim (L: 19-74%; Z: 57-73%; MZ:
      83-97%); however, the oil filled soft gel products (n = 5) met or were above
      their label claim (L: 98-122%; Z: 117-162%; MZ: 97-319%). We also identified that
      the carotenoid content of the oil filled capsules were stable over time (e.g., L
      average percentage change: -1.7%), but the powder filled supplements degraded
      over time (e.g., L average percentage change: -17.2%). These data are consistent
      with our previous work, and emphasize the importance of using carotenoid
      interventions in oil based formulas rather than powder filled formulas.

PMID- 29039802
TI  - Effects of an Advocacy Trial on Food Industry Salt Reduction Efforts-An Interim
      Process Evaluation.
AB  - The decisions made by food companies are a potent factor shaping the nutritional
      quality of the food supply. A number of non-governmental organizations (NGOs)
      advocate for corporate action to reduce salt levels in foods, but few data define
      the effectiveness of advocacy. This present report describes the process
      evaluation of an advocacy intervention delivered by one Australian NGO directly
      to food companies to reduce the salt content of processed foods. Food companies
      were randomly assigned to intervention (n = 22) or control (n = 23) groups.
      Intervention group companies were exposed to pre-planned and opportunistic
      communications, and control companies to background activities. Seven pre-defined
      interim outcome measures provided an indication of the effect of the intervention
      and were assessed using intention-to-treat analysis. These were supplemented by
      qualitative data from nine semi-structured interviews. The mean number of public
      communications supporting healthy food made by intervention companies was 1.5
      versus 1.8 for control companies (p = 0.63). Other outcomes, including the mean
      number of news articles, comments and reports (1.2 vs. 1.4; p = 0.72), a
      published nutrition policy (23% vs. 44%; p = 0.21), public commitment to the
      Australian government's Food and Health Dialogue (FHD) (41% vs. 61%; p = 0.24),
      evidence of a salt reduction plan (23% vs. 30%; p = 0.56), and mean number of
      communications with the NGO (15 vs. 11; p = 0.28) were also not significantly
      different. Qualitative data indicated the advocacy trial had little effect. The
      absence of detectable effects of the advocacy intervention on the interim markers
      indicates there may be no impact of the NGO advocacy trial on the primary outcome
      of salt reduction in processed foods.

PMID- 29039803
TI  - The Influence of the Polymer Amount on the Biological Properties of PCL/ZrO2
      Hybrid Materials Synthesized via Sol-Gel Technique.
AB  - Organic/inorganic hybrid materials are attracting considerable attention in the
      biomedical area. The sol-gel process provides a convenient way to produce many
      bioactive organic-inorganic hybrids. Among those, poly(e-caprolactone)/zirconia
      (PCL/ZrO2) hybrids have proved to be bioactive with no toxic materials. The aim
      of this study was to investigate the effects of these materials on the cellular
      response as a function of the PCL content, in order to evaluate their potential
      use in the biomedical field. For this purpose, PCL/ZrO2 hybrids containing 6, 12,
      24, and 50 wt % of PCL were synthesized by the sol-gel method. The effects of
      their presence on the NIH-3T3 fibroblast cell line carrying out direct cell
      number counting, MTT, cell damage assays, flow cytometry-based analysis of cell
      cycle progression, and immunoblotting experiments. The results confirm and extend
      the findings that PCL/ZrO2 hybrids are free from toxicity. The hybrids containing
      12 and 24 wt % PCL, (more than 6 and 50 wt % ones) enhance cell proliferation
      when compared to pure ZrO2 by affecting cell cycle progression. The finding that
      the content of PCL in PCL/ZrO2 hybrids differently supports cell proliferation
      suggests that PCL/ZrO2 hybrids could be useful tools with different potential
      clinical applications.

PMID- 29039804
TI  - Review and Analysis of Peak Tracking Techniques for Fiber Bragg Grating Sensors.
AB  - Fiber Bragg Grating (FBG) sensors are among the most popular elements for fiber
      optic sensor networks used for the direct measurement of temperature and strain.
      Modern FBG interrogation setups measure the FBG spectrum in real-time, and
      determine the shift of the Bragg wavelength of the FBG in order to estimate the
      physical parameters. The problem of determining the peak wavelength of the FBG
      from a spectral measurement limited in resolution and noise, is referred as the
      peak-tracking problem. In this work, the several peak-tracking approaches are
      reviewed and classified, outlining their algorithmic implementations: the methods
      based on direct estimation, interpolation, correlation, resampling, transforms,
      and optimization are discussed in all their proposed implementations. Then, a
      simulation based on coupled-mode theory compares the performance of the main peak
      tracking methods, in terms of accuracy and signal to noise ratio resilience.

PMID- 29039805
TI  - Ferritin Heavy Subunit Silencing Blocks the Erythroid Commitment of K562 Cells
      via miR-150 up-Regulation and GATA-1 Repression.
AB  - Erythroid differentiation is a complex and multistep process during which an
      adequate supply of iron for hemoglobinization is required. The role of ferritin
      heavy subunit, in this process, has been mainly attributed to its capacity to
      maintain iron in a non-toxic form. We propose a new role for ferritin heavy
      subunit (FHC) in controlling the erythroid commitment of K562 erythro-myeloid
      cells. FHC knockdown induces a change in the balance of GATA transcription
      factors and significantly reduces the expression of a repertoire of erythroid
      specific genes, including alpha- and gamma-globins, as well as CD71 and CD235a
      surface markers, in the absence of differentiation stimuli. These molecular
      changes are also reflected at the morphological level. Moreover, the ability of
      FHC-silenced K562 cells to respond to the erythroid-specific inducer hemin is
      almost completely abolished. Interestingly, we found that this new role for FHC
      is largely mediated via regulation of miR-150, one of the main microRNA
      implicated in the cell-fate choice of common erythroid/megakaryocytic
      progenitors. These findings shed further insight into the biological properties
      of FHCand delineate a role in erythroid differentiation where this protein does
      not act as a mere iron metabolism-related factor but also as a critical regulator
      of the expression of genes of central relevance for erythropoiesis.

PMID- 29039806
TI  - Algal Foams Applied in Fixed-Bed Process for Lead(II) Removal Using Recirculation
      or One-Pass Modes.
AB  - The incorporation of brown algae into biopolymer beads or foams for metal
      sorption has been previously reported. However, the direct use of these biomasses
      for preparing foams is a new approach. In this study, two kinds of porous foams
      were prepared by ionotropic gelation using algal biomass (AB, Laminaria digitata)
      or alginate (as the reference) and applied for Pb(II) sorption. These foams
      (manufactured as macroporous discs) were packed in filtration holders (simulating
      fixed-bed column) and the system was operated in either a recirculation or a one
      pass mode. Sorption isotherms, uptake kinetics and sorbent reuse were studied in
      the recirculation mode (analogous to batch system). In the one-pass mode
      (continuous fixed-bed system), the influence of parameters such as flow rate,
      feed metal concentration and bed height were investigated on both sorption and
      desorption. In addition, the effect of Cu(II) on Pb(II) recovery from binary
      solutions was also studied in terms of both sorption and desorption. Sorption
      isotherms are well fitted by the Langmuir equation while the pseudo-second order
      rate equation described well both sorption and desorption kinetic profiles. The
      study of material regeneration confirms that the reuse of the foams was feasible
      with a small mass loss, even after 9 cycles. In the one-pass mode, for alginate
      foams, a slower flow rate led to a smaller saturation volume, while the effect of
      flow rate was less marked for AB foams. Competitive study suggests that the foams
      have a preference for Pb(II) over Cu(II) but cannot selectively remove Pb(II)
      from the binary solution.

PMID- 29039807
TI  - Modeling Calculation and Synthesis of Alumina Whiskers Based on the Vapor
      Deposition Process.
AB  - This study simulated the bulk structure and surface energy of Al2O3 based on the
      density of states (DOS) and studied the synthesis and microstructure of one
      dimensional Al2O3 whiskers. The simulation results indicate that the (001)
      surface has a higher surface energy than the others. The growth mechanism of
      Al2O3 whiskers follows vapor-solid (VS) growth. For the (001) surface with the
      higher surface energy, the driving force of crystal growth would be more intense
      in the (001) plane, and the alumina crystal would tend to grow preferentially
      along the direction of the (001) plane from the tip of the crystal. The Al2O3
      grows to the shape of whisker with [001] orientation, which is proved both
      through modeling and experimentation.

PMID- 29039809
TI  - Diffusive and Metabolic Constraints to Photosynthesis in Quinoa during Drought
      and Salt Stress.
AB  - Quinoa (Chenopodium quinoa Willd.) has been proposed as a hardy alternative to
      traditional grain crops in areas with warm-to-hot climates that are likely to
      experience increased drought and salt stress in the future. We characterised the
      diffusive and metabolic limitations to photosynthesis in quinoa exposed to
      drought and salt stress in isolation and combination. Drought-induced pronounced
      stomatal and mesophyll limitations to CO2 transport, but quinoa retained
      photosynthetic capacity and photosystem II (PSII) performance. Saline water (300
      mmol NaCl-equivalent to 60% of the salinity of sea-water) supplied in identical
      volumes to the irrigation received by the control and drought treatments induced
      similar reductions in stomatal and mesophyll conductance, but also reduced
      carboxylation of ribulose-1,5-bisphosphate carboxylase/oxygenase, regeneration of
      ribulose-1,5-bisphosphate, increased non-photochemical dissipation of energy as
      heat and impaired PSII electron transport. This suggests that ion toxicity
      reduced PN via interference with photosynthetic enzymes and degradation of
      pigment-protein complexes within the thylakoid membranes. The results of this
      study demonstrate that the photosynthetic physiology of quinoa is resistant to
      the effects of drought, but quinoa may not be a suitable crop for areas subject
      to strong salt stress or irrigation with a concentration of saline water
      equivalent to a 300 mmol NaCl solution.

PMID- 29039808
TI  - A Diagnosis of Denial: How Mental Health Classification Systems Have Struggled to
      Recognise Family Violence as a Serious Risk Factor in the Development of Mental
      Health Issues for Infants, Children, Adolescents and Adults.
AB  - Child and adolescent mental health services (CAMHS) routinely overlook assessing
      for, and providing treatment to, infants and children living with family
      violence, despite family violence being declared endemic across the globe. As
      contemporary neuro-developmental research recognises the harm of being exposed to
      early relational trauma, key international diagnostic texts such as the DSM-5 and
      ICD-10 struggle to acknowledge or appreciate the relational complexities inherent
      in addressing family violence and its impacts during childhood. These key texts
      directly influence thinking, funding and research imperatives in adult services
      as well as CAMHS, however, they rarely reference family violence. Their emphasis
      is to pathologise conditions over exploring causality which may be attributable
      to relational violence. Consequently, CAMHS can miss important indicators of
      family violence, misdiagnose disorders and unwittingly, not address unacceptable
      risks in the child's caregiving environment. Notwithstanding urgent safety
      concerns, ongoing exposure to family violence significantly heightens the
      development of mental illness amongst children. CAMHS providers cannot and should
      not rely on current diagnostic manuals alone. They need to act now to see family
      violence as a significant and important risk factor to mental health and to treat
      its impacts on children before these develop into enduring neurological
      difficulties.

PMID- 29039810
TI  - Effects of Moisture and Particle Size on Quantitative Determination of Total
      Organic Carbon (TOC) in Soils Using Near-Infrared Spectroscopy.
AB  - Near-Infrared Spectroscopy is a cost-effective and environmentally friendly
      technique that could represent an alternative to conventional soil analysis
      methods, including total organic carbon (TOC). Soil fertility and quality are
      usually measured by traditional methods that involve the use of hazardous and
      strong chemicals. The effects of physical soil characteristics, such as moisture
      content and particle size, on spectral signals could be of great interest in
      order to understand and optimize prediction capability and set up a robust and
      reliable calibration model, with the future perspective of being applied in the
      field. Spectra of 46 soil samples were collected. Soil samples were divided into
      three data sets: unprocessed, only dried and dried, ground and sieved, in order
      to evaluate the effects of moisture and particle size on spectral signals. Both
      separate and combined normalization methods including standard normal variate
      (SNV), multiplicative scatter correction (MSC) and normalization by closure
      (NCL), as well as smoothing using first and second derivatives (DV1 and DV2),
      were applied to a total of seven cases. Pretreatments for model optimization were
      designed and compared for each data set. The best combination of pretreatments
      was achieved by applying SNV and DV2 on partial least squares (PLS) modelling.
      There were no significant differences between the predictions using the three
      different data sets (p < 0.05). Finally, a unique database including all three
      data sets was built to include all the sources of sample variability that were
      tested and used for final prediction. External validation of TOC was carried out
      on 16 unknown soil samples to evaluate the predictive ability of the final
      combined calibration model. Hence, we demonstrate that sample preprocessing has
      minor influence on the quality of near infrared spectroscopy (NIR) predictions,
      laying the ground for a direct and fast in situ application of the method. Data
      can be acquired outside the laboratory since the method is simple and does not
      need more than a simple band ratio of the spectra.

PMID- 29039811
TI  - Nutrients in Infancy: Progress and Prospects.
AB  - This monograph, based on a special issue of Nutrients, contains 31 papers-5
      reviews and 26 original publications-that reflect the wide spectrum of current
      research on nutrients and infancy [...].

PMID- 29039813
TI  - Transcriptomic Analysis of Long Non-Coding RNAs and Coding Genes Uncovers a
      Complex Regulatory Network That Is Involved in Maize Seed Development.
AB  - Long non-coding RNAs (lncRNAs) have been reported to be involved in the
      development of maize plant. However, few focused on seed development of maize.
      Here, we identified 753 lncRNA candidates in maize genome from six seed samples.
      Similar to the mRNAs, lncRNAs showed tissue developmental stage specific and
      differential expression, indicating their putative role in seed development.
      Increasing evidence shows that crosstalk among RNAs mediated by shared microRNAs
      (miRNAs) represents a novel layer of gene regulation, which plays important roles
      in plant development. Functional roles and regulatory mechanisms of lncRNAs as
      competing endogenous RNAs (ceRNA) in plants, particularly in maize seed
      development, are unclear. We combined analyses of consistently altered 17
      lncRNAs, 840 mRNAs and known miRNA to genome-wide investigate potential lncRNA
      mediated ceRNA based on "ceRNA hypothesis". The results uncovered seven novel
      lncRNAs as potential functional ceRNAs. Functional analyses based on their
      competitive coding-gene partners by Gene Ontology (GO) and KEGG biological
      pathway demonstrated that combined effects of multiple ceRNAs can have major
      impacts on general developmental and metabolic processes in maize seed. These
      findings provided a useful platform for uncovering novel mechanisms of maize seed
      development and may provide opportunities for the functional characterization of
      individual lncRNA in future studies.

PMID- 29039814
TI  - Microstructuring of Mesoporous Titania Films Loaded with Silver Salts to Enhance
      the Photocatalytic Degradation of Methyl Blue under Visible Light.
AB  - The microstructuring of the distribution of silver nanoparticles (NPs) in
      mesoporous titania films loaded with silver salts, using two-beam interference
      lithography leading to 1 Dimension (1D) grating, induces variations in the
      photocatalytic efficiency. The influence of the structuration was tested on the
      degradation of methyl blue (MB) under ultraviolet (UV) and visible illumination,
      giving rise to a significant improvement of the photocatalytic efficiency. The
      periodic distribution of the NPs was characterized by transmission electron
      microscopy (TEM), high-angle annular dark field scanning transmission electron
      microscopy (HAADF-STEM) and scanning electron microscopy (SEM).

PMID- 29039815
TI  - Vibration Noise Modeling for Measurement While Drilling System Based on FOGs.
AB  - Aiming to improve survey accuracy of Measurement While Drilling (MWD) based on
      Fiber Optic Gyroscopes (FOGs) in the long period, the external aiding sources are
      fused into the inertial navigation by the Kalman filter (KF) method. The KF
      method needs to model the inertial sensors' noise as the system noise model. The
      system noise is modeled as white Gaussian noise conventionally. However, because
      of the vibration while drilling, the noise in gyros isn't white Gaussian noise
      any more. Moreover, an incorrect noise model will degrade the accuracy of KF.
      This paper developed a new approach for noise modeling on the basis of dynamic
      Allan variance (DAVAR). In contrast to conventional white noise models, the new
      noise model contains both the white noise and the color noise. With this new
      noise model, the KF for the MWD was designed. Finally, two vibration experiments
      have been performed. Experimental results showed that the proposed vibration
      noise modeling approach significantly improved the estimated accuracies of the
      inertial sensor drifts. Compared the navigation results based on different noise
      model, with the DAVAR noise model, the position error and the toolface angle
      error are reduced more than 90%. The velocity error is reduced more than 65%. The
      azimuth error is reduced more than 50%.

PMID- 29039812
TI  - Molecular Aspects of Circadian Pharmacology and Relevance for Cancer
      Chronotherapy.
AB  - The circadian timing system (CTS) controls various biological functions in
      mammals including xenobiotic metabolism and detoxification, immune functions,
      cell cycle events, apoptosis and angiogenesis. Although the importance of the CTS
      is well known in the pharmacology of drugs, it is less appreciated at the
      clinical level. Genome-wide studies highlighted that the majority of drug target
      genes are controlled by CTS. This suggests that chronotherapeutic approaches
      should be taken for many drugs to enhance their effectiveness. Currently
      chronotherapeutic approaches are successfully applied in the treatment of
      different types of cancers. The chronotherapy approach has improved the
      tolerability and antitumor efficacy of anticancer drugs both in experimental
      animals and in cancer patients. Thus, chronobiological studies have been of
      importance in determining the most appropriate time of administration of
      anticancer agents to minimize their side effects or toxicity and enhance
      treatment efficacy, so as to optimize the therapeutic ratio. This review focuses
      on the underlying mechanisms of the circadian pharmacology i.e.,
      chronopharmacokinetics and chronopharmacodynamics of anticancer agents with the
      molecular aspects, and provides an overview of chronotherapy in cancer and some
      of the recent advances in the development of chronopharmaceutics.

PMID- 29039816
TI  - Dampness and Moisture Problems in Norwegian Homes.
AB  - The occurrence of dampness and mold in the indoor environment is associated with
      respiratory-related disease outcomes. Thus, it is pertinent to know the magnitude
      of such indoor environment problems to be able to estimate the potential health
      impact in the population. In the present study, the moisture damage in 10,112
      Norwegian dwellings was recorded based on building inspection reports. The levels
      of moisture damage were graded based on a condition class (CC), where CC0 is
      immaculate and CC1 acceptable (actions not required), while CC2 and CC3 indicate
      increased levels of damage that requires action. Of the 10,112 dwellings
      investigated, 3125 had verified moisture or mold damage. This amounts to 31% of
      the surveyed dwellings. Of these, 27% had CC2 as the worst grade, whereas 4% had
      CC3 as the worst grade level. The room types and building structures most prone
      to moisture damage were (in rank order) crawl spaces, basements, un-insulated
      attics, cooling rooms, and bathrooms. The high proportion of homes with moisture
      damage indicate a possible risk for respiratory diseases in a relatively large
      number of individuals, even if only the more extensive moisture damages and those
      located in rooms where occupants spend the majority of their time would have a
      significant influence on adverse health effects.

PMID- 29039817
TI  - Replacing Nitrogen by Sulfur: From Structurally Disordered Eumelanins to
      Regioregular Thiomelanin Polymers.
AB  - The oxidative polymerization of 5,6-dihydroxybenzothiophene (DHBT), the sulfur
      analog of the key eumelanin building block 5,6-dihydroxyindole (DHI), was
      investigated to probe the role of nitrogen in eumelanin build-up and properties.
      Unlike DHI, which gives a typical black insoluble eumelanin polymer on oxidation,
      DHBT is converted to a grayish amorphous solid (referred to as thiomelanin) with
      visible absorption and electron paramagnetic resonance properties different from
      those of DHI melanin. Mass spectrometry experiments revealed gradational mixtures
      of oligomers up to the decamer level. Quite unexpectedly, nuclear magnetic
      resonance (NMR) analysis of the early oligomer fractions indicated linear, 4-,
      and 7-linked structures in marked contrast with DHI, which gives highly complex
      mixtures of partially degraded oligomers. Density functional theory (DFT)
      calculations supported the tendency of DHBT to couple via the 4- and 7-positions.
      These results uncover the role of nitrogen as a major determinant of the
      structural diversity generated by the polymerization of DHI, and point to
      replacement by sulfur as a viable entry to regioregular eumelanin-type materials
      for potential applications for surface functionalization by dip coating.

PMID- 29039818
TI  - The Role of B Cell Targeting in Chronic Graft-Versus-Host Disease.
AB  - Chronic graft-versus-host disease (cGVHD) is a leading cause of late morbidity
      and mortality following allogeneic stem cell transplantation. Current therapies,
      including corticosteroids and calcineurin inhibitors, are only effective in
      roughly 50% of cases; therefore, new treatment strategies are under
      investigation. What was previously felt to be a T cell disease has more recently
      been shown to involve activation of both T and B cells, as well as a number of
      cytokines. With a better understanding of its pathophysiology have come more
      expansive preclinical and clinical trials, many focused on B cell signaling. This
      report briefly reviews our current understanding of cGVHD pathophysiology and
      reviews clinical and preclinical trials with B cell-targeted agents.

PMID- 29039820
TI  - Drugs for common bacterial infections in adults.

PMID- 29039821
TI  - Tisagenlecleucel (Kymriah) for ALL.

PMID- 29039822
TI  - Ribociclib (Kisqali) for advanced or metastatic breast cancer.

PMID- 29039823
TI  - [Chronic heart failure: New challenges and new perspectives].
AB  - Chronic heart failure is an important global public health problem. This is
      associated with extremely poor prognosis, high readmission rates, and substantial
      treatment costs in patients. The paper gives the main aspects of the setting-up
      of a specialized service to patients with heart failure.

PMID- 29039824
TI  - [Influence of modifiable cardiovascular risk factors on antihypertensive therapy
      efficiency escape].
AB  - AIM: To evaluate the influence of cardiovascular risk factors on antihypertensive
      therapy (AHT) efficiency escape (EE). SUBJECTS AND METHODS: Data on 59 patients
      with grades 1-3 hypertension (Stages I-II) were analyzed. During chosen AHT, 24
      hour blood pressure monitoring was done at baseline, 1 and 3 months after
      beginning the observation to identify/rule out the AHT EE phenomenon. RESULTS:
      The AHT EE group (Group 1) as compared with the group that needed no therapy
      correction within 3 months (Group 2) was observed to have the following: elevated
      fasting blood glucose levels (FBGL) (5.8+/-0.8 vs 5.3+/-0.7 mmol/l; p=0.008) and
      higher impaired glucose tolerance (IGT) rates (8 (27.6%) vs 4 (13.3%) cases
      (p=0.03)); a more number of smoking patients (8 (27.6%) vs 3 (10%) cases;
      p=0.02); a larger number of patients with a compromised family history of
      cardiovascular diseases (17 (58.6%) vs 11 (36%); p=0.02). Furthermore, in Group 1
      baseline average systolic blood pressure during 24 hours (SBP-24) proved to be
      higher than that in Group 2 (127.4+/-4.2 vs 122.4+/-6.8 mm Hg; p=0.002). Odds
      ratio (OR) for developing the EE phenomenon increased by 60% with a rise of 0.5
      mmol in FBGL (OR, 1.60; 95% confidence interval (CI), 1.06 to 2.4; p=0.02) and by
      18% with an increase of 1 mm Hg in baseline SBP-24 (OR, 1.18; 95% CI, 1.05 to
      1.33; p=0.004). Multivariate analysis indicated that the independent predictors
      of AHT EE were a compromised family history (OR, 3.7; 95% CI, 1.1 to 12.1;
      p=0.03) and IGT (OR, 4.1; 95% CI, 1.02 to 16.4; p=0.04). CONCLUSION: AHT EE was
      influenced by FBGL, IGT, smoking, a compromised family history, and baseline SBP
      24 level.

PMID- 29039819
TI  - Single Domain Antibodies as New Biomarker Detectors.
AB  - Biomarkers are defined as indicators of biological processes, pathogenic
      processes, or pharmacological responses to a therapeutic intervention. Biomarkers
      have been widely used for early detection, prediction of response after
      treatment, and for monitoring the progression of diseases. Antibodies represent
      promising tools for recognition of biomarkers, and are widely deployed as
      analytical tools in clinical settings. For immunodiagnostics, antibodies are now
      exploited as binders for antigens of interest across a range of platforms. More
      recently, the discovery of antibody surface display and combinatorial chemistry
      techniques has allowed the exploration of new binders from a range of animals,
      for instance variable domains of new antigen receptors (VNAR) from shark and
      variable heavy chain domains (VHH) or nanobodies from camelids. These single
      domain antibodies (sdAbs) have some advantages over conventional murine
      immunoglobulin owing to the lack of a light chain, making them the smallest
      natural biomarker binders thus far identified. In this review, we will discuss
      several biomarkers used as a means to validate diseases progress. The potential
      functionality of modern singe domain antigen binders derived from
      phylogenetically early animals as new biomarker detectors for current diagnostic
      and research platforms development will be described.

PMID- 29039825
TI  - [Time course of changes in left ventricular twist in the presence of idiopathic
      left bundle branch block during exercise testing].
AB  - AIM: To investigate left ventricular (LV) deformation properties, rotation, and
      twist during a bicycle ergometer exercise test among patients with idiopathic
      left bundle branch block (LBBB). SUBJECTS AND METHODS: Thirty-four patients with
      idiopathic LBBB having a mean QRS duration of 153+/-24 msec were examined. A
      control group included 18 apparently healthy volunteers. All the patients and
      apparently healthy individuals underwent echocardiography to determine LV
      hemodynamic parameters, deformity, rotation and twist at rest and after exercise
      test. RESULTS: As compared with the control, the idiopathic LBBB group at rest
      showed decreases in LV global longitudinal deformity (-15.6+/-4.7 and -18.4+/
      3.1%, respectively; p=0.037), apical rotation (4.59+/-4.2 degrees  and 8.99+/
      3.68 degrees ; p=0.0067) and twist (9.08+/-4.59 degrees  and 13.96+/-4.61 degrees
      ; p=0.0156), whereas there were no differences in LV ejection fraction and end
      systolic and end-diastolic volumes. After exercise testing there were no
      augmentations in basal and apical rotation and resulting DeltaTwist in the
      idiopathic LBBB group compared with the control (-2.05+/-8.35 and 4.66+/-8.49%;
      p=0.0463). The described changes in LV rotation and twist during exercise testing
      occurred in the presence of elevated pulmonary artery systolic pressure (PASP) in
      the LBBB group compared with the control (41.6+/-3.81 and 32.4+/-3.81 mm Hg,
      respectively; p=0.0201). CONCLUSION: Decreases in LV basal, apical and resulting
      twist may lead to elevated PASP in patients with idiopathic LBBB during exercise.

PMID- 29039826
TI  - [Endothelial immune activation and functional state in patients with hypertensive
      disease].
AB  - AIM: To investigate the nitric oxide (NO) system, the activity of endothelial NO
      synthase (e-NOS) and inducible NO synthase (i-NOS) in relation to the levels of
      tumor necrosis factor-alpha (TNF- alpha) and its soluble receptor type I (sTNFRI)
      depending on the grade of hypertensive disease (HD). SUBJECTS AND METHODS: A
      total of 317 patients, including 284 patients aged 30 to 65 years (mean age
      54.7+/-0.58 years) with Grades 1-3 HD who had not previously received regular
      antihypertensive therapy and 33 apparently healthy individuals, were examined at
      Kharkov City Clinical Hospital Eleven. Immune activation was judged by the serum
      levels of the proinflammatory cytokine TNF-alpha in all the examinees and y those
      of sTNFRI, which were measured by enzyme immunoassay. To study the endothelial
      functional state, the level of stable end metabolites of nitric oxide, that of S
      nitrosothiol and the activity of NO synthases were biochemically determined in
      100 patients from this group. A control group consisted of 16 apparently healthy
      individuals. RESULTS: There were increases in the circulating levels of
      proinflammatory cytokines (TNF-alpha, sTNFRI), the content of S-nitrosothiol and
      the activity of i-NOS. At the same time, there were decreases in the activity of
      e-NOS and the level of end nitric oxide metabolites, such as nitrites and
      nitrates. CONCLUSION: In patients with HD, the end metabolites of nitric oxide
      decrease, which indirectly shows a reduction in its vasoactive part, and the
      stable NO metabolite S-nitrosothiol increases. This is associated with enhanced
      NO oxidation under conditions of oxidative stress and endothelial dysfunction.
      The higher amount of S-nitrosothiol in the examinees may be associated with
      increased i-NOS. The immunoinflammatory activation mediated by the
      proinflammatory cytokines, particularly by the enhanced activity of TNF-alpha and
      sTNFRI, has been proven to play a role.

PMID- 29039827
TI  - [Impact of hyperglycemia on the results of percutaneous coronary interventions in
      patients with acute ST-segment elevation myocardial infarction].
AB  - AIM: To investigate the impact of hyperglycemia on the results of percutaneous
      coronary interventions (PCIs) in patients with acute ST-segment elevation
      myocardial infarction (ASTEMI). SUBJECTS AND METHODS: A study group consisted of
      511 patients with hyperglycemia (blood glucose level (BGL) >=7.77 mmol/L) who
      underwent primary PCIs in the period from 2005 to 2015. A comparison group
      included 579 patients (BGL >=7.77 mmol/L). RESULTS: Assessment of the results of
      hospital interventions revealed that the mortality rates in patients with
      hyperglycemia proved to be higher than in those with normal BGL (6.5 and 2.6%,
      respectively; p=0.002). No differences were found in the rates of stent
      thrombosis (1 and 1.4%; p=0.541) and recurrent myocardial infarction (1.2 and
      1.6%; p=0.591). Major adverse cardiac events, including death, recurrent
      infarction, and stent thrombosis, were more frequently determined in the
      hyperglycemic patients (7.6 and 4.3%; p=0.020). No-reflow phenomenon
      statistically significantly more frequently developed in the patients with
      hyperglycemia (6.8 and 3.3%; p=0.007). Binary logistic regression analysis showed
      that the presence of hyperglycemia served as an independent predictor of hospital
      mortality (odds ratio (OR) 2.6; 95% confidence interval (CI), 1.4 to 4.8;
      p=0.002). The application of a random probability sampling technique revealed
      that mortality remained statistically significantly higher in the hyperglycemic
      patients than in the normoglycemic individuals at admission (6.7 and 2.6%;
      r=0.011). CONCLUSION: PCIs in patients with ASTEMI and hyperglycemia are
      characterized by higher mortality rates and the risk of major adverse cardiac
      events. Admission hyperglycemia is an independent predictor of hospital
      mortality.

PMID- 29039828
TI  - [Clinical, laboratory and instrumental criteria for myocarditis, established in
      comparison with myocardial biopsy: A non-invasive diagnostic algorithm].
AB  - AIM: To determine the diagnostic value of different clinical, laboratory, and
      instrumental signs in the diagnosis of myocarditis in patients with the picture
      of idiopathic arrhythmias, dilated cardiomyopathy (DCM) and in a comparison group
      when comparing with myocardial morphological examination. SUBJECTS AND METHODS: A
      study group included 100 patients (35 women; mean age, 44.7+/-12.5 years) with
      idiopathic arrhythmias (n=20) and DCM as a syndrome (n=100). All underwent
      myocardial morphological examination: endomyocardial biopsy (EMB) (n=71),
      intraoperative biopsy (n=13), study of the explanted heart (n=6), and autopsy
      (n=11). A comparison group consisted of 50 patients (25 women; mean age, 53.7+/
      11.7 years) with non-inflammatory diseases of the heart (left ventricular end
      diastolic dimension <6.0 cm, ejection fraction >50%) who underwent open-heart
      surgery (n=47), EMB (n=2), or autopsy (n=1). The investigators also performed
      polymerase chain reaction for cardiotropic viral DNA in the blood and myocardium,
      anticardiac antibody (ACA) identification, myocardial scintigraphy (n=26),
      coronary angiography (n=47), magnetic resonance imaging (MRI) (n=25), and
      multislice computed tomography of the heart (n=45). The diagnostic value of the
      extended spectrum of clinical, laboratory, and instrumental markers for
      myocarditis was estimated. RESULTS: Active/borderline myocarditis was diagnosed
      in 76% of the patients in the study group (75.5% in the arrhythmia subgroup and
      76.3% in the DCM one) and in 24.3% of those in the comparison group (p<0.001). A
      viral genome in the myocardium was detected statistically significantly less
      frequently in the study group than that in the comparison one (40.2 and 65%,
      respectively; p<0.01): in 46.6% in the DCM subgroup and 15.8% in the arrhythmia
      one. An ACA set (sensitivity, specificity, and predictive value of positive and
      negative test results (45.7, 80, 80.4, and 45%, respectively)) was of the
      greatest diagnostic importance in identifying myocarditis; antibodies to
      cardiomyocyte nuclei in a titer of 1:160-1:320 had the highest specificity
      (93.3%). A specificity above 70% was seen for a full medical history triad (acute
      onset, an association between onset and infection, a symptom duration of less
      than one year), systemic immune manifestations, anginas in the history and
      elevated anti-O-streptolysin levels, systemic blood changes, Q waves/QS complexes
      on ECGs, local hypokinesias, pericardial effusion, atriomegalia (in arrhythmias),
      angina/ischemia with intact coronary arteries, and focal perfusion defects during
      myocardial scintigraphy. A sensitivity higher than 50% was observed for age over
      40 years (differential diagnosis with genetic forms), acute onset, a correlation
      with infection, and delayed contrast agent accumulation, as evidenced by
      MSCT/MRI. CONCLUSION: When the incidence of myocarditis is similar in the
      arrhythmia and DCM subgroups, the viral genome detection rate is statistically
      significantly higher in DCM. Among the non-invasive markers, an ACA set (high
      sensitivity and specificity) is of the greatest diagnostic value in the diagnosis
      of myocarditis. The diagnostic rule based on counting the number of scores has
      been developed, which makes it possible to individually establish the risk of
      myocarditis in patients with idiopathic arrhythmias and DCM for both the
      determination of indications for biopsy and the lack of the possibility of its
      performance. The risk of myocarditis is high if there are 5-7 scores; that is
      close to 100% if there are 8 scores or more.

PMID- 29039829
TI  - [Factors for the development of persistent postoperative cognitive dysfunction in
      patients undergoing coronary artery bypass surgery under extracorporeal
      circulation].
AB  - AIM: To analyze the factors contributing to the increased risk of persistent
      postoperative cognitive dysfunction (POCD) in patients undergoing coronary artery
      bypass surgery (CABS) under extracorporeal circulation (EC). SUBJECTS AND
      METHODS: 257 male patients aged 45 to 69 years with coronary heart disease (CHD)
      undergoing elective CABS under EC were examined. In addition to conventional
      clinical examination, all the patients underwent neuropsychological testing 3-5
      days before, 7-14 days and 1 year after CABS. Persistent POCD was diagnosed if
      there was a 20% decline in cognitive domains at 1-year postoperatively versus
      preoperatively in 20% of the tests of an entire neuropsychological battery.
      Binary logistic regression analysis was applied to identify the factors
      supposedly increasing the risk of persistent POCD. RESULTS: It was found that
      high baseline cognitive status, early POCD after CABG under EC, low adherence to
      the prescribed treatment regimen, as well as progressive carotid artery (CA)
      stenosis could predict with a high (85%) probability that persistent POCD might
      develop at 1 year after surgery. CONCLUSION: The findings are suggestive of the
      multifactorial origin of persistent POCD, a significant role in the development
      of which is played by not only the preoperative cognitive status, but also by
      postoperative factors, such as the degree of adherence to the prescribed
      treatment regimen, early POCD, and progressive CA stenosis.

PMID- 29039830
TI  - [Role of AGTR1 A/C polymorphism in the development of atrial fibrillation].
AB  - AIM: To investigate the AGTR1 A/C polymorphism associated with atrial
      fibrillation (AF) to form risk groups among patients who are prone to this
      disease. SUBJECTS AND METHODS: 90 probands with a confirmed diagnosis of AF and
      their 144 first-, second-, and third-degree relatives were examined. These
      families made up a study group. A control group was formed of 100 apparently
      healthy individuals without a history of cardiovascular diseases. Collection of
      medical history data and complaints, electrocardiography, electrocardiogram
      monitoring, as well as molecular genetic analysis, thyroid hormone tests were
      done in all the patients. RESULTS: No statistically significant data on the
      correlation between the AGTR1 A/C polymorphism and the development of AF were
      obtained in any patient subgroup. The obtained results can be due to the genetic
      features of a Siberian population, which are dependent on climatic conditions and
      geographical location, and confirm that AF is a heterogeneous disease.
      CONCLUSION: There were no statistically significant differences between the
      patients in the study group and those in the control group. Our findings suggest
      the heterogeneity of AF and confirm its multifactorial nature.

PMID- 29039831
TI  - [Comparative analysis of mortality from acute forms of ischemic heart disease
      during a 15-year period in the Russian Federation and the United States and the
      factors influencing its formation].
AB  - AIM: To comparatively analyze the registered mortality rates from coronary heart
      disease (CHD) as a whole, as well as myocardial infarction (MI) and other acute
      forms of CHD during a 15-year period in the Russian Federation (RF, 2000-2014)
      and the United States of America (USA, 1999-2013). MATERIAL AND METHODS: Primary
      data were obtained from the database of the RF State Statistics Service, the
      World Health Organization Mortality Database, Human Mortality Database, then
      converted into standardized mortality rates and are presented in three age groups
      (30+, 30-49, and 50+ years old) in men and women separately. RESULTS: The
      analysis revealed a substantial excess of the registered mortality rates from CHD
      in the RF versus in the USA, as well as a lower incidence of MI and a higher
      incidence of other acute CHD forms registered as the cause of death. It also
      showed considerable differences in the structure of registered types of MI as the
      cause of mortality. CONCLUSION: The differences found in the mortality rates from
      CHD, MI, and other acute forms of CHD in the RF and the USA can be explained by
      objective (the higher prevalence of cardiovascular risk factors, the higher and
      earlier incidence of CHD in the RF, as well as differences in the organization of
      medical care and, as a result, actually higher mortality rates from CHD in
      Russia) and subjective (differences in approaches to statistically developing a
      population-based mortality rate, as well as defects in filling out the medical
      documents and coding the causes of death) factors.

PMID- 29039832
TI  - [Gender peculiarities of the risk of cardiovascular diseases in a population with
      symptoms of depression in Siberia (the WHO MONICA-psychosocial program)].
AB  - AIM: To identify gender differences in the prevalence of depression in an open
      population of individuals aged 25-64 years and to evaluate its impact on the risk
      of cardiovascular diseases (CVD) in the population of Siberia. SUBJECTS AND
      METHODS: A random representative sample of a 25-64-year-old Novosibirsk
      population (657 men and 689 women) was surveyed within the framework of the third
      screening of the WHO MONICA-psychosocial program in 1994. The screening program
      included sociodemographic data registration and depression detection. Over a 16
      year study period, women had myocardial infarction (MI) in 15 cases and stroke in
      35 cases and men had these conditions in 30 and 22 cases, respectively. RESULTS:
      In the open 25-64-year-old population, depression was detected in 54.5% of the
      women and in 29% of the men; major depression was present in 11.8% of the women
      and 3.1% of the men (chi2=66.724; upsilon=2; p=0.0001). The risk of MI in the
      depressed patients was higher in the women (hazard ratio (HR)=2.5) than in the
      men (HR=2); when social parameters and age are included in the model, only a
      trend towards the impact of depression on the risk of MI persisted in the women
      (HR=3.4; p>0.05) and the men were observed to have a 1.6-fold higher risk for MI.
      The greatest risk of MI was seen in the men (HR=6.8) and women (HR=6.3) at the
      age of 55-64 years, as well as in the men who had incomplete secondary or primary
      education (HR=3.2); in blue-collar workers (HR=6.7), in the men who were single
      (HR=3.6), divorced (HR=4.5), or widowed (HR=6). The risk of stroke in the
      depressed patients during a 16-year study period was greater in the men (HR=5.8)
      than in the women (HR=4.6); after adjusting for age and social gradient, the risk
      of stroke in the women was higher in both the population and those who were aged
      55-64 years (HR=8.5 and 6.9, respectively) than that in the men (HR=4.2 and 3.1,
      respectively). Among the men, the risk of stroke was higher in those who had
      primary education (HR=8.8), were widowed (HR=8.4) or divorced (HR=2.7).
      CONCLUSION: The women are much more susceptible to depression than are the men.
      The risk of MI with depression is higher in the women than in the men; at the
      same time, the risk of stroke is higher in the men than in the women. The picture
      is opposite in the older age group. The risk of CVD in the depressed men is
      exacerbated by a social gradient; these relationships have not been revealed in
      the women.

PMID- 29039833
TI  - [Genetic determinants of hypertension in two national cohorts of Mountain
      Shoria].
AB  - AIM: To estimate the prevalence of the genotypes of the candidate genes ACE (I/D,
      rs4646994), ADRB1 (Ser49Gly, A/G, rs1801252) ADRA2B (I/D), MTHFR (C677T,
      Ala222Val, rs1801133), and eNOS (4b/4a) and their association with hypertension
      in two ethnic groups of Mountain Shoria. SUBJECTS AND METHODS: A clinical and
      epidemiological study was conducted in a population compactly living in the hard
      to-reach areas of Mountain Shoria (the settlements of Orton, Ust-Kabyrza, and
      Sheregesh of the Kemerovo Region). A continuous method was used to survey 1178
      residents from the above settlements; the sample consisted of adults (aged 18
      years and older), 565 people were genotyped. RESULTS: The prevalence of
      hypertension among the population of Mountain Shoria was 42.3%. The incidence of
      this disease among the Shorians was lower (39.9%) than that among the
      representatives of non-indigenous people (46.1%). The ethnically justified
      peculiarities of the association of ADRA2B and ACE I/D polymorphisms with
      hypertension were established. There were fewer patients with hypertension among
      ACE ID and ADRA2B DD genotype carriers in the cohort of the Shorians than in that
      of the non-indigenous population: 40.6% versus 58.6% and 38.3% versus 64%,
      respectively. Conversely, there were more hypertensive patients among the
      carriers of the homozygous ACE DD genotype in the native ethnic group (60%) than
      in the non-indigenous one (37.1%). CONCLUSION: Adverse prognostic ACE DD, ADRB1
      AA, MTHFR TT, and eNOS 4a/4a genotypes were more frequently observed in the non
      indigenous ethnic groups; the ADRA2B DD genotype was more common in the native
      population. Hypertension was associated with the ACE DD, MTHFR CT, and ADRB1 AA
      genotypes in the native ethnic group and with the ACE ID genotype in the non
      indigenous population.

PMID- 29039834
TI  - [Renal function in patients receiving long-term warfarin therapy: A five-year
      prospective follow-up].
AB  - AIM: To investigate the prognostic value of renal function and to estimate
      glomerular filtration rate (GFR) changes during a 5-year follow-up of patients
      receiving warfarin therapy. SUBJECTS AND METHODS: 200 patients (124 men, 76
      women) mainly from a group at high risk for thromboembolic events (mean CHA2DS2
      VASc scores, 3.25+/-1.89) were examined. The patients' mean age was 62.3+/-9.4
      years; the follow-up period was 5 years. 74% of the patients received warfarin
      monotherapy (international normalized ratio (INR) 2.0 to 3.0); 36% took vitamin K
      antagonists in combination with one or two antiplatelet agents. The CKD-EPI
      formula was used to estimate GFR in all the patients at baseline and throughout
      the investigation once a year. RESULTS: GFR less than 70.9 ml/min/1.73 m2 was
      found to be a predictor of fatal and nonfatal thrombotic events. The decreased
      GFR was unassociated with the development of major and clinically relevant
      hemorrhagic complications within 5 years of warfarin therapy. The initial decline
      in renal function (GFR <70.9 ml/min/1.73 m2) was associated only with an
      increased rate of recurrent minor hemorrhagic complications. During 5-year
      warfarin therapy, there was a significant decrease in GFR from 97.1+/-24.85 to
      91.9+/-28.9 ml/min/1.73 m2; at the same time, a rapidly progressive loss of renal
      function (GFR >=3 ml/min/1.73 m2/year) was recorded in 25.9% of the patients.
      Discriminant analysis showed that a baseline left ventricular ejection fraction
      of <40% was a predictor for the rapidly progressive loss of kidney function.
      CONCLUSION: Long-term warfarin therapy achieved the therapeutic range for INR is
      safe in the environment of the created patronage system. The initial decrease in
      GFR is a predictor of thrombotic events and is unassociated with an increased
      risk of bleeding.

PMID- 29039835
TI  - [Quality of life in patients with lower extremity atherosclerosis during standard
      treatment and therapeutic angiogenesis].
AB  - AIM: To compare the impact of standard conservative treatment (SCT) and its
      combination with therapeutic angiogenesis for 3 to 5 years on quality of life in
      patients with Stage II (according to the classification developed by A.V.
      Pokrovsky-Fontaine) lower extremity atherosclerosis. SUBJECTS AND METHODS: 92
      patients (69 men and 23 women) (mean age 65.2+/-7.7 years) were examined and
      divided into 2 groups of 46 people each. Only SCT (statins at an individually
      adjusted dose, antiaggregants, and graded exercise walking 3 to 5 km daily were
      used in Group 1; while Group 2 received SCT in combination with double injection
      of a plasmid-based VEGF165 gene drug (1.2 mg) into the ischemic limb muscles. The
      Russian version of the standard SF-36 questionnaire was applied; pain-free
      walking distances were measured before treatment and then every year; limb
      preservation and survival rates were determined in the patients. RESULTS: It was
      determined that standard treatment did not significantly affect patients' quality
      of life throughout the follow-up period. Addition of gene therapy leads to a
      significant improvement in both physical (p=0.00001) and psychological
      (p=0.00002) health components just in the first year of the follow-up. This is
      achieved through a significant (500%) increase in the average leg pain-free
      walking distance; p=0.007). CONCLUSION: The obtained result is consistently high
      throughout the subsequent period. There was no statistically significant
      difference in survival rates between the groups; limb preservation remained
      comparable.

PMID- 29039836
TI  - [Chronic thromboembolic pulmonary hypertension developed in a female patient with
      lupus erythematosus and secondary antiphospholipid syndrome].
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the potentially
      curable forms of pulmonary hypertension, in which pulmonary thromboendarterectomy
      is the gold standard treatment. However, over the last decade, great attention
      has been given to a combined therapeutic approach including both drug therapy and
      surgical treatment and the application of endovascular technologies. This
      clinical case demonstrates the diagnostic difficulties of CTEPH and the
      opportunities of a comprehensive approach to therapy for the disease with
      mandatory assessment of preoperative surgical and medical treatment in order to
      improve the patient status and to prepare for surgery.

PMID- 29039837
TI  - [A patient with severe idiopathic pulmonary arterial hypertension: Is there a way
      out?]
AB  - The paper considers a clinical example of current therapy for idiopathic
      pulmonary arterial hypertension in a female patient with its clinical
      deterioration. It shows the tactics of switching from one drug (bosentan) to
      others (macitentan) within in the same pathogenetic therapy group (endothelin
      receptor antagonists). The latest pulmonary hypertension classification (Nice,
      2013) is presented. The current strategies of pathogenetic therapy for pulmonary
      hypertension are discussed.

PMID- 29039838
TI  - [Atrial septal aneurysm: Evolution of diagnostic and clinical judgements].
AB  - The article discusses anatomical and clinical judgements on atrial septal
      aneurysm (ASA) as a primary cardiac structural abnormality. It presents current
      approaches to the classification of ASA and its echocardiographic diagnosis.
      Special attention is focused on the clinical significance of ASA as an isolated
      anomaly and concurrent with other structural abnormalities of the heart,
      especially from the standpoint of a risk of cardioembolic stroke.

PMID- 29039839
TI  - [The role of integrated assessment of the indicators of external respiration
      function in cardiac surgical patients].
AB  - This literature review dedicated to the importance of an integrated assessment of
      external respiratory function in cardiovascular diseases (CVDs), including an
      analysis of up-to-date techniques, such as spirometry, body plethysmography,
      examination of the diffusing capacity of the lung, determination of O2
      consumption with evaluation of the effectiveness of pulmonary ventilation. It
      considers the pathogenetic components of impairments in pulmonary ventilation and
      gas exchange, which develop in different CVDs, as well as during and after
      cardiac surgery. The authors analyze the results of international investigations
      and their own experience, which emphasize the prognostic value of lung function
      tests and suggest that there is a need for a comprehensive functional assessment
      of the respiratory system in cardiac surgical patients for their effective
      preoperative preparation, assessment and reduction of operational risks, and
      improvement of the prognosis of surgical treatment.

PMID- 29039840
TI  - [Use of loop diuretics in heart failure: Current aspects].
AB  - Loop diuretics take the lead in the treatment of patients with symptomatic heart
      failure. Torasemide is the most effective and safe loop diuretic with the optimal
      pharmacokinetic profile, the additional properties associated with simultaneous
      blockade of the renin-angiotensin-aldosterone system and with the antiadrenergic
      effects of the drug, its positive impact on myocardial fibrosis and minimal
      severe potential negative effects. Sustained-release torasemide provides a more
      comfortable removal of excess liquid and does not deteriorate quality of life.

PMID- 29039841
TI  - [Non-vitamin K antagonist oral anticoagulants for heart diseases].
AB  - Non-vitamin K antagonist oral anticoagulants (NOASs) are highly effective drugs
      that prevent venous thrombosis and stroke in atrial fibrillation. Their use has
      difficulties that are associated with the need for laboratory control and with
      the influence of many factors on the activity of these medications. The emerged
      direct oral anticoagulants have some advantages over NOACs. Nevertheless, there
      are a number of pathological conditions, in which NOACs remain first-line drugs.
      These include prosthetic mechanical heart valves, a glomerular filtration rate
      less than 60 mL/min/1.73 m2, and left atrial thrombus.

PMID- 29039842
TI  - A virtual climate library of surface temperature over North America for 1979
      2015.
AB  - The most comprehensive continuous-coverage modern climatic data sets, known as
      reanalyses, come from combining state-of-the-art numerical weather prediction
      (NWP) models with diverse available observations. These reanalysis products
      estimate the path of climate evolution that actually happened, and their use in a
      probabilistic context-for example, to document trends in extreme events in
      response to climate change-is, therefore, limited. Free runs of NWP models
      without data assimilation can in principle be used for the latter purpose, but
      such simulations are computationally expensive and are prone to systematic
      biases. Here we produce a high-resolution, 100-member ensemble simulation of
      surface atmospheric temperature over North America for the 1979-2015 period using
      a comprehensive spatially extended non-stationary statistical model derived from
      the data based on the North American Regional Reanalysis. The surrogate climate
      realizations generated by this model are independent from, yet nearly
      statistically congruent with reality. This data set provides unique opportunities
      for the analysis of weather-related risk, with applications in agriculture,
      energy development, and protection of human life.

PMID- 29039843
TI  - Acetoclastic Methanosaeta are dominant methanogens in organic-rich Antarctic
      marine sediments.
AB  - Despite accounting for the majority of sedimentary methane, the physiology and
      relative abundance of subsurface methanogens remain poorly understood. We
      combined intact polar lipid and metagenome techniques to better constrain the
      presence and functions of methanogens within the highly reducing, organic-rich
      sediments of Antarctica's Adelie Basin. The assembly of metagenomic sequence data
      identified phylogenic and functional marker genes of methanogens and generated
      the first Methanosaeta sp. genome from a deep subsurface sedimentary environment.
      Based on structural and isotopic measurements, glycerol dialkyl glycerol
      tetraethers with diglycosyl phosphatidylglycerol head groups were classified as
      biomarkers for active methanogens. The stable carbon isotope (delta13C) values of
      these biomarkers and the Methanosaeta partial genome suggest that these organisms
      are acetoclastic methanogens and represent a relatively small (0.2%) but active
      population. Metagenomic and lipid analyses suggest that Thaumarchaeota and
      heterotrophic bacteria co-exist with Methanosaeta and together contribute to
      increasing concentrations and delta13C values of dissolved inorganic carbon with
      depth. This study presents the first functional insights of deep subsurface
      Methanosaeta organisms and highlights their role in methane production and
      overall carbon cycling within sedimentary environments.

PMID- 29039844
TI  - Soil microbial diversity drives the priming effect along climate gradients: a
      case study in Madagascar.
AB  - The priming effect in soil is proposed to be generated by two distinct
      mechanisms: 'stoichiometric decomposition' and/or 'nutrient mining' theories.
      Each mechanism has its own dynamics, involves its own microbial actors, and
      targets different soil organic matter (SOM) pools. The present study aims to
      evaluate how climatic parameters drive the intensity of each priming effect
      generation mechanism via the modification of soil microbial and physicochemical
      properties. Soils were sampled in the center of Madagascar, along climatic
      gradients designed to distinguish temperature from rainfall effects. Abiotic and
      biotic soil descriptors were characterized including bacterial and fungal
      phylogenetic composition. Potential organic matter mineralization and PE were
      assessed 7 and 42 days after the beginning of incubation with 13C-enriched wheat
      straw. Both priming mechanisms were mainly driven by the mean annual temperature
      but in opposite directions. The priming effect generated by stoichiometric
      decomposition was fostered under colder climates, because of soil enrichment in
      less developed organic matter, as well as in fast-growing populations.
      Conversely, the priming effect generated by nutrient mining was enhanced under
      warmer climates, probably because of the lack of competition between slow-growing
      populations mining SOM and fast-growing populations for the energy-rich residue
      entering the soil. Our study leads to hypotheses about the consequences of
      climate change on both PE generation mechanisms and associated consequences on
      soil carbon sequestration.

PMID- 29039845
TI  - RNA sequencing analysis of activated macrophages treated with the anti-HIV ABX464
      in intestinal inflammation.
AB  - RNA-Seq enables the generation of extensive transcriptome information providing
      the capability to characterize transcripts (including alternative isoforms and
      polymorphism), to quantify expression and to identify differential regulation in
      a single experiment. To reveal the capacity of new anti-HIV ABX464 candidate in
      modulating the expression of genes, datasets were generated and validated using
      RNA-seq approach. This comprehensive dataset will be useful to deepen the
      comprehensive understanding of the progression of human immunodeficiency virus
      (HIV) associated with mucosal damage in the gastrointestinal (GI) tract and
      subsequent inflammation, providing an opportunity to generate new therapies,
      diagnoses, and preventive strategies.

PMID- 29039848
TI  - High-throughput DFT calculations of formation energy, stability and oxygen
      vacancy formation energy of ABO3 perovskites.
AB  - ABO3 perovskites are oxide materials that are used for a variety of applications
      such as solid oxide fuel cells, piezo-, ferro-electricity and water splitting.
      Due to their remarkable stability with respect to cation substitution, new
      compounds for such applications potentially await discovery. In this work, we
      present an exhaustive dataset of formation energies of 5,329 cubic and distorted
      perovskites that were calculated using first-principles density functional
      theory. In addition to formation energies, several additional properties such as
      oxidation states, band gap, oxygen vacancy formation energy, and thermodynamic
      stability with respect to all phases in the Open Quantum Materials Database are
      also made publicly available. This large dataset for this ubiquitous crystal
      structure type contains 395 perovskites that are predicted to be
      thermodynamically stable, of which many have not yet been experimentally
      reported, and therefore represent theoretical predictions. The dataset thus opens
      avenues for future use, including materials discovery in many research-active
      areas.

PMID- 29039846
TI  - Gut bacterial communities of diarrheic patients with indications of
      Clostridioides difficile infection.
AB  - We present bacterial 16S rRNA gene datasets derived from stool samples of 44
      patients with diarrhea indicative of a Clostridioides difficile infection. For 20
      of these patients, C. difficile infection was confirmed by clinical evidence.
      Stool samples from patients originating from Germany, Ghana, and Indonesia were
      taken and subjected to DNA isolation. DNA isolations of stool samples from 35
      asymptomatic control individuals were performed. The bacterial community
      structure was assessed by 16S rRNA gene analysis (V3-V4 region). Metadata from
      patients and control individuals include gender, age, country, presence of
      diarrhea, concomitant diseases, and results of microbiological tests to diagnose
      C. difficile presence. We provide initial data analysis and a dataset overview.
      After processing of paired-end sequencing data, reads were merged, quality
      filtered, primer sequences removed, reads truncated to 400 bp and dereplicated.
      Singletons were removed and sequences were sorted by cluster size, clustered at
      97% sequence similarity and chimeric sequences were discarded. Taxonomy to each
      operational taxonomic unit was assigned by BLASTn searches against Silva database
      123.1 and a table was constructed.

PMID- 29039849
TI  - Targeted metabolomics and medication classification data from participants in the
      ADNI1 cohort.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disease presenting
      major health and economic challenges that continue to grow. Mechanisms of disease
      are poorly understood but significant data point to metabolic defects that might
      contribute to disease pathogenesis. The Alzheimer Disease Metabolomics Consortium
      (ADMC) in partnership with Alzheimer Disease Neuroimaging Initiative (ADNI) is
      creating a comprehensive biochemical database for AD. Using targeted and non-
      targeted metabolomics and lipidomics platforms we are mapping metabolic pathway
      and network failures across the trajectory of disease. In this report we present
      quantitative metabolomics data generated on serum from 199 control, 356 mild
      cognitive impairment and 175 AD subjects enrolled in ADNI1 using AbsoluteIDQ-p180
      platform, along with the pipeline for data preprocessing and medication
      classification for confound correction. The dataset presented here is the first
      of eight metabolomics datasets being generated for broad biochemical
      investigation of the AD metabolome. We expect that these collective metabolomics
      datasets will provide valuable resources for researchers to identify novel
      molecular mechanisms contributing to AD pathogenesis and disease phenotypes.

PMID- 29039852
TI  - Th(iv) and Ce(iv) napthylsalophen sandwich complexes: characterization of unusual
      thorium fluorescence in solution and solid-state.
AB  - The synthesis, characterization, and electronic spectroscopy of two ML2 sandwich
      complexes, where M = Ce(iv) or Th(iv) and L = napthylsalophen2- are described.
      The ThL2 complex, unlike the isovalent CeL2, complex possesses unusual
      fluorescence properties in both solution and solid-state. These observations are
      explained with TD-DFT.

PMID- 29039851
TI  - Quantifying person-level brain network functioning to facilitate clinical
      translation.
AB  - Although advances in neuroimaging have yielded insights into the intrinsic
      organization of human brain networks and their relevance to psychiatric and
      neurological disorders, there has been no translation of these insights into
      clinical practice. One necessary step toward clinical translation is identifying
      a summary metric of network function that is reproducible, reliable, and has
      known normative data, analogous to normed neuropsychological tests. Our aim was
      therefore to establish the proof of principle for such a metric, focusing on the
      default mode network (DMN). We compared three candidate summary metrics: global
      clustering coefficient, characteristic path length, and average connectivity.
      Across three samples totaling 322 healthy, mostly Caucasian adults, average
      connectivity performed best, with good internal consistency (Cronbach's
      alpha=0.69-0.70) and adequate eight-week test-retest reliability (intra-class
      coefficient=0.62 in a subsample N=65). We therefore present normative data for
      average connectivity of the DMN and its sub-networks. These proof of principle
      results are an important first step for the translation of neuroimaging to
      clinical practice. Ultimately, a normed summary metric will allow a single
      patient's DMN function to be quantified and interpreted relative to normative
      peers.

PMID- 29039853
TI  - Construction of Sierpinski triangles with the coexistence of C60 or MnPc
      molecules.
AB  - Sierpinski triangles up to the fourth order were successfully prepared using
      4,4''-dicyano-1,1':3',1''-terphenyl molecules and Fe or Co atoms with the
      coexistence of the third molecules (C60 or MnPc) on a reconstructed Au(111)
      substrate. Sierpinski triangles could be disturbed and restored by C60 molecules
      after annealing at 400 and 360 K, respectively. The dispersed MnPc molecules did
      not affect the formation of Sierpinski triangles when annealed at high
      temperatures. The selective adsorption of MnPc molecules at certain holes of
      Sierpinski triangles was observed.

PMID- 29039850
TI  - Systematic Review: Disease Activity Indices in Eosinophilic Esophagitis.
AB  - OBJECTIVES: There is no clear consensus regarding the most appropriate measure(s)
      of eosinophilic esophagitis (EoE) disease activity. We aimed to identify all
      scoring indices used for the measurement of disease activity in EoE, appraise
      their operating properties, and discuss their value as outcome measures. METHODS:
      MEDLINE, EMBASE, and CENTRAL (The Cochrane library) were searched from inception
      to 11 May 2016. Randomized controlled trials (RCTs), cohort, case-control, and
      cross-sectional studies that reported outcomes to measure EoE disease activity or
      response to treatment were eligible. Operating properties of histologic,
      endoscopic, and patient reported/symptomatic and health-related quality of life
      measures were critically appraised according to guidelines proposed by the United
      States Food and Drug Administration. RESULTS: Of 4,373 citations, 130 studies
      were eligible, of which 20 were RCTs. Although no index met all evaluative
      criteria, we found that: (1) the EoE histologic scoring system (EoEHSS) is the
      most valid histologic measure; (2) the Endoscopic Reference Score (EREFS) is the
      most reliable and responsive endoscopy measure; and (3) the Eosinophilic
      Esophagitis Activity Index (EEsAI) or the Dysphagia Symptoms Questionnaire (DSQ)
      had superior construct validity and responsiveness in adults. The Pediatric
      Quality of Life Inventory EoE was the most valid pediatric symptomatic measure.
      CONCLUSIONS: Current evidence supports the use of the EoEHSS and EREFS as
      measures of histologic and endoscopic EoE disease activity, respectively, and the
      EEsAI, DSQ, or Pediatric Quality of Life Inventory EoE as measures of adult and
      pediatric symptoms. Additional research is needed to optimize endpoint
      configuration to facilitate development of new therapies.

PMID- 29039854
TI  - Sugar hydrazide imides: a new family of glycosidase inhibitors.
AB  - The preparation of a novel type of iminosugar including a hydrazide imide moiety
      is described. The sugar hydrazide imides (3S,4S,5R,6R)-1-amino-3,4,5-trihydroxy-6
      (hydroxymethyl)-2-iminopiperidine acetate and (3S,4S,5R,6R)-3,4,5-trihydroxy-6
      (hydroxymethyl)-2-imino-1-(methylamino)piperidine acetate presented here behave
      as inhibitors of alpha/beta-glucosidases in the low micromolar concentration
      range. The former inhibitor displays a pH-dependent inhibition of beta
      glucosidase. The N-methylated counterpart behaves as an anomer-selective
      competitive micromolar inhibitor of alpha-glucosidase.

PMID- 29039855
TI  - Temperature dependence of the hydrogen bond network in trimethylamine N-oxide and
      guanidine hydrochloride-water solutions.
AB  - We present an X-ray Compton scattering study on aqueous trimethylamine N-oxide
      (TMAO) and guanidine hydrochloride solutions (GdnHCl) as a function of
      temperature. Independent from the concentration of the solvent, Compton profiles
      almost resemble results for liquid water as a function of temperature. However,
      the number of hydrogen bonds per water molecule extracted from the Compton
      profiles suggests a decrease of hydrogen bonds with rising temperature for all
      studied samples, and the differences between water and the solutions are weak.
      Nevertheless, the data indicate a reduced bond weakening with rising TMAO
      concentration up to 5 M of 7.2% compared to 8% for pure water. In contrast, the
      addition of GdnHCl appears to behave differently for concentrations up to 3.1 M
      with a weaker impact on the temperature response of the hydrogen bond structure.

PMID- 29039856
TI  - Visible light-driven photogeneration of hydrogen sulfide.
AB  - The combined use of a singlet oxygen photosensitizer and 1,3
      diarylisobenzothiophene enables efficient generation of hydrogen sulfide under
      visible light illumination.

PMID- 29039857
TI  - Acid/base-controllable fluorescent molecular switches based on cryptands and
      basic N-heteroaromatics.
AB  - Two kinds of fluorescent BMP32C10-based cryptands 1 and 2 have been developed.
      Cryptand 1 contains a binaphthol group, while cryptand 2 bears a coumarin group
      in their third arms. Based on this design, novel self-assemblies constructed from
      cryptand 1 or 2 and basic N-heteroaromatic guests 3-6 were successfully obtained.
      Moreover, the threading/dethreading processes of the host-guest complexes could
      be well switched by the alternate addition of acid/base, and accompanied by
      concurrent changes in fluorescence.

PMID- 29039858
TI  - A pyrene based fluorescent turn-on chemosensor: aggregation-induced emission
      enhancement and application towards Fe3+ and Fe2+ recognition.
AB  - A pyrene-based probe bearing benzothiazole ionophore (Py-BTZ) was synthesised as
      a "turn-on" fluorescent chemosensor for the detection of Fe3+ and Fe2+ ions in
      CH3CN : H2O (1 : 1, v/v) solvent mixes. The chemosensor showed optical as well as
      colorimetric changes towards Fe3+ and Fe2+ ions along with a remarkable
      enhancement in fluorescence emission. The detection limit of Py-BTZ towards Fe3+
      and Fe2+ ions was found to be 2.61 MUM and 2.06 MUM, respectively. The binding of
      Py-BTZ with Fe3+ and Fe2+ was determined by using FT-IR experiments.
      Interestingly, Py-BTZ shows aggregation induced emission enhancement (AIEE)
      properties in polar solvent mixes such as CH3CN : H2O (1 : 1, v/v).

PMID- 29039859
TI  - Atomically thin non-layered nanomaterials for energy storage and conversion.
AB  - After the discovery of graphene, two-dimensional nanomaterials with atomic
      thickness and large lateral size have attracted tremendous research interest due
      to their high specific surface areas, exotic electronic structures, and
      fascinating physical and chemical properties. Even though recent studies are
      mainly focused on atomically thin nanomaterials with layered structures due to
      their easy preparation and characterization, the investigation of non-layered
      nanomaterials is also proceeding as new types of ultrathin nanostructures are
      constantly being created, such as metals, metal oxides, metal chalcogenides, some
      transition metal dichalcogenides, and perovskites. Here in this review, we
      comprehensively summarize the preparation methods for atomically thin non-layered
      nanomaterials, study their exotic electronic structures, introduce electronic
      structure manipulation strategies, and provide an overview of their applications
      in energy storage and conversion, with particular emphasis on lithium-ion
      batteries, sodium-ion batteries, catalysis of hydrogen evolution, oxygen
      evolution, CO2 reduction, CO oxidation reactions, etc. The central theme of this
      review is to provide correlation among the materials synthesis, structural and
      electronic properties, and their major applications. Finally, based on current
      research progress, we propose future directions yet to be explored for enhanced
      properties and novel functionalities in practical applications.

PMID- 29039860
TI  - Generation and transformation of a hemi-iminal-based metal-organic Fe(ii)
      structure obtained via subcomponent self-assembly in water.
AB  - We report the synthesis and characterization of a coordination architecture with
      a Fe(ii) center obtained by subcomponent self-assembly in water. The complex is
      based on very rare hemi-iminal ligands spontaneously generated from commercially
      available materials. The complex can be further transformed into another species
      by oxidation reaction of both the metal center and organic ligand.

PMID- 29039861
TI  - Design of encapsulated hosts and guests for highly efficient blue and green
      thermally activated delayed fluorescence OLEDs based on a solution-process.
AB  - The molecular aggregation and exciton-polaron interaction of the host-guest
      system were successfully restricted by efficient molecular encapsulation. The
      solution-processed blue and green TADF OLEDs have been realized with external
      quantum efficiencies above 23% by employing the encapsulated TADF host and guest
      as emission layers.

PMID- 29039862
TI  - A pair of 3D enantiotopic zinc(ii) complexes based on two asymmetric achiral
      ligands.
AB  - Enantiomorphism and enantioselectivity are critical in biology and many other
      applications. Herein, we report two 3D chiral MOFs {[Zn6(MIDPPA)3(1,2,4
      btc)3(NO2)3(H2O)3](H2O)7}n (1L and 1R) based on achiral ligands with high
      enantiomeric excess and a novel topological type. The internal mechanism of
      spontaneous chiral symmetry breaking, during the crystallization of chiral MOFs
      based on achiral ligands, is elucidated for the first time from both structural
      and theoretical aspects. Hydrogen bonds are found to play a key role in the
      spontaneous symmetry breaking of chiral MOFs. Also, DFT calculations support our
      findings from the aspects of total energies and HOMO-LUMO energy gaps. Both 1L
      and 1R, exhibiting green fluorescence, present a non-centrosymmetric polar
      packing arrangement, resulting in good ferroelectric behaviors and second-order
      nonlinear optical effects.

PMID- 29039863
TI  - Synthesis of carbazole-based BODIPY dimers showing red fluorescence in the solid
      state.
AB  - Carbazole-based BODIPY dimers 2a-g were synthesized via direct arylation. They
      showed red-shifted solid-state fluorescence spectra as compared with the
      corresponding monomer. In addition, unsymmetrical dimers 2d, 2f, and 2g with two
      different substituents showed red fluorescence with improved quantum yields in
      the solid state.

PMID- 29039864
TI  - Effects of pulsed laser irradiation on gold-coated silver nanoplates and their
      antibacterial activity.
AB  - Gold-coated silver nanoplates, when subjected to pulsed laser irradiation,
      changed their shape from triangular to spherical, accompanied by a shift of their
      extinction spectra. The simple single crystal structure of the silver nanoplates
      changed to multiple small crystal domains. The ratio of silver to gold of the
      particles also changed from 22 : 1 to 4.5 : 1, enabling more silver to be
      released. As a result, the antibacterial activity of the gold-coated silver
      nanoplates was significantly increased after pulsed laser irradiation.

PMID- 29039865
TI  - Photophysical properties of three coordinated copper(i) complexes bearing 1,10
      phenanthroline and a monodentate phosphine ligand.
AB  - We report the synthesis and photophysical properties of Cu(i) complexes with 1,10
      phenanthroline (phen) and monodentate phosphine ligands. Single crystal X-ray
      structural analysis revealed that these have three-coordinated trigonal planar
      geometries. We also found that one of them, [Cu(phen)(Johnphos)]BF4 (Johnphos = 2
      (di-tert-butylphosphino)biphenyl), is considerably emissive both in solution and
      solid states. The emission maximum wavelength of the emission of the complex is
      580 nm, and the lifetime of the emission is 2 MUs in solution. Moreover, we have
      systematically investigated the photophysical and redox properties of four
      coordinate complexes [Cu(NN)(P)2]+ in addition to three-coordinate complexes
      [Cu(NN)(P)]+. Charge transfer transitions play a key role in the photophysics of
      these complexes.

PMID- 29039866
TI  - N-Acylsuccinimides: twist-controlled, acyl-transfer reagents in Suzuki-Miyaura
      cross-coupling by N-C amide bond activation.
AB  - The palladium-catalyzed Suzuki-Miyaura cross-coupling of N-acylsuccinimides as
      versatile acyl-transfer reagents via selective amide N-C bond cleavage is
      reported. The method is user-friendly since it employs commercially-available,
      air-stable reagents and catalysts. The cross-coupling is enabled by half-twist of
      the amide bond in N-acylsuccinimides. These highly effective, crystalline acyl
      transfer reagents present major advantages over perpendicularly twisted N
      acylglutarimides, including low price of the succinimide activating ring,
      selective metal insertion under redox neutral conditions and high stability of
      the amide bond towards reaction conditions. Mechanistic studies indicate that
      oxidative addition is the rate limiting step in this widely applicable protocol.

PMID- 29039867
TI  - Water-soluble, neutral 3,5-diformyl-BODIPY with extended fluorescence lifetime in
      a self-healable chitosan hydrogel.
AB  - 3,5-Diformyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (3,5-diformyl-BODIPY) can
      be used as an efficient biofunctional cross-linker to generate a new class of
      chitosan-based hydrogels with fluorescence resonance energy transfer (FRET)
      dynamics and good solubility in water. The hydrogel was fully characterized by FT
      IR, UV-vis, fluorescence, FE-SEM, AFM, rheology and picosecond time-resolved
      spectroscopic techniques. The self-healing ability was demonstrated by
      rheological recovery and macroscopic and microscopic observations. The
      fluorescence lifetime was found to increase in aqueous solution of the BODIPY
      chitosan hydrogel compared to the 3,5-diformyl-BODIPY monomer. Calculations based
      on experimental results such as red-shift and decreased intensity of the emission
      spectrum of highly dye-concentrated hydrogel in comparison to dilute hydrogels,
      together with changes in the fluorescence lifetime of the hydrogel at different
      concentration of dyes, suggest that the BDP-CS hydrogels fluorescence dynamics
      obey the Forster resonance energy transfer (FRET). Improvements in mechanical and
      photochemical properties and the acceptable values of BODIPY fluorescence
      lifetime in the hydrogel matrix indicate the utility of the newly synthesized
      hydrogels for biomedical applications.

PMID- 29039868
TI  - Inkjet-printed barcodes for a rapid and multiplexed paper-based assay compatible
      with mobile devices.
AB  - This study reports a simple, rapid, low-cost, robust, and multiplexed barcoded
      paper-based assay (BPA) compatible with mobile devices. An inkjet printer and an
      XYZ dispensing platform were used to realize mass-manufacturing of barcoded paper
      based analytical devices (BPADs) with high precision and efficiency. We designed
      a new group of barcodes and developed an application (APP) for the reading of the
      new code. The new barcodes possess a 16 times higher coding capacity than the
      standard Codabar code in our experiment on drug residue detection. The BPA system
      allows applications in the assays of blood-transmitted infections, drug residues
      in milk and multiplex nucleic acids. The whole detection process and the readout
      of the results can be completed within 10 minutes. The limit of detection for
      enrofloxacin (ENR) (8 ng mL-1) satisfies the requirements of drug residue
      monitoring. Its high rapidity, simplicity, efficiency and selectivity make the
      BPA system extremely suitable to be applied in rapid and on-site detection.

PMID- 29039870
TI  - It Is Time to Change the Status Quo: Limiting Orthopedic Surgery Residency
      Applications.

PMID- 29039869
TI  - Electrodiagnostic Testing in the Diagnosis and Management of Carpal Tunnel
      Syndrome.

PMID- 29039871
TI  - Superior Capsular Reconstruction.
AB  - Superior capsular reconstruction (SCR) of the shoulder has recently gained
      popularity as an option for joint-preserving shoulder surgery for patients with
      an irreparable rotator cuff tear. In the absence of glenohumeral arthritis,
      rotator cuff tear irreparability should only be diagnosed for most patients after
      a careful diagnostic arthroscopy. Superior capsular reconstruction adds
      biological, passive, superior constraint to the glenohumeral joint, thereby
      optimizing the rotator cuff force couples and improving joint kinematics. At
      short-term follow-up, SCR has been shown to be effective for pain relief and
      restoration of active shoulder motion, even in the worst cases of shoulder
      dysfunction (true shoulder pseudoparalysis). The rapid early adoption and
      expansion of SCR is justified by its excellent anatomical, biomechanical, and
      short-term clinical results. The techniques for arthroscopic SCR using dermal
      allograft continue to improve; however, the operation remains technically
      demanding. Patients with risk factors for irreparability and who might benefit
      from reconstruction of the superior capsule should be counseled about the
      operation as an additional, joint-preserving procedure that can be done in
      conjunction with arthroscopic, partial rotator cuff repair. [Orthopedics. 2017;
      40(5):271-280.].

PMID- 29039874
TI  - ?

PMID- 29039873
TI  - ?
AB  - Age- and gender-specific reference intervals are pivotal to ensure appropriate
      interpretation of plasma alkaline phosphatase activities in the lower range
      Hypophosphatasia (HPP) is an inborn error of metabolism caused by loss-of
      function mutations of the ALPL gene that mainly express alkaline phosphatase
      (ALP) in bone and liver. The clinical expression of HPP is highly variable and is
      classified into six different forms mainly affecting bone and tooth
      mineralization. The prognosis for each of these HPP forms depends upon the
      severity of the skeletal disease which reflects the age at presentation. The
      biochemical hallmark of HPP is low plasma ALP activity (hypophosphatasemia);
      however, HPP is often misdiagnosed because of low awareness and sometimes absence
      of age- and gender-specific ALP reference intervals. Children and adolescents
      have higher ALP levels in comparison with adults. Reliable reference intervals
      are pivotal for any clinical laboratory test. Harmonized age- and gender-specific
      plasma ALP reference intervals ought to be used to ensure appropriate
      interpretation of plasma ALP activities in the lower range.

PMID- 29039875
TI  - ?

PMID- 29039876
TI  - ?

PMID- 29039877
TI  - ?

PMID- 29039878
TI  - ?

PMID- 29039879
TI  - ?

PMID- 29039880
TI  - ?

PMID- 29039881
TI  - ?

PMID- 29039882
TI  - ?

PMID- 29039884
TI  - Erratum: Wangerin et al. (2015)

PMID- 29039883
TI  - Volume-targeted versus pressure-limited ventilation in neonates.
AB  - BACKGROUND: Damage caused by lung overdistension (volutrauma) has been implicated
      in the development of bronchopulmonary dysplasia (BPD). Modern neonatal
      ventilation modes can target a set tidal volume as an alternative to traditional
      pressure-limited ventilation (PLV) using a fixed inflation pressure. Volume
      targeted ventilation (VTV) aims to produce a more stable tidal volume in order to
      reduce lung damage and stabilise the partial pressure of carbon dioxide (pCO2).
      OBJECTIVES: To determine whether VTV compared with PLV leads to reduced rates of
      death and death or BPD in newborn infants and to determine whether use of VTV
      affected outcomes including air leak, cranial ultrasound findings and
      neurodevelopment. SEARCH METHODS: We used the standard search strategy of
      Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials
      (CENTRAL 2016, Issue 12), MEDLINE via PubMed (1966 to 13 January 2017), Embase
      (1980 to 13 January 2017) and CINAHL (1982 to 13 January 2017). We also searched
      clinical trials databases, conference proceedings and the reference lists of
      retrieved articles for randomised controlled trials and quasi-randomised trials.
      We contacted the principal investigators of studies to obtain supplementary
      information. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing
      VTV versus PLV in infants of less than 44 weeks' postmenstrual age and reporting
      clinically relevant outcomes. DATA COLLECTION AND ANALYSIS: We assessed risk of
      bias for each trial using Cochrane methodology. We evaluated quality of evidence
      for each outcome using GRADE criteria. We tabulated mortality, rates of BPD,
      short-term clinical outcomes and long-term developmental outcomes. STATISTICS:
      for categorical outcomes, we calculated typical estimates for risk ratios (RR),
      risk differences (RD) and number needed to treat for an additional beneficial
      outcome (NNTB). For continuous variables, we calculated typical estimates for
      mean differences (MD). We used 95% confidence intervals (CI) and assumed a fixed
      effect model for meta-analysis. MAIN RESULTS: Twenty randomised trials met our
      inclusion criteria; 16 parallel trials (977 infants) and four cross-over trials
      (88 infants). No studies were blinded and the quality of evidence for outcomes
      assessed varied from moderate to low.We found no difference in the primary
      outcome, death before hospital discharge, between VTV modes versus PLV modes
      (typical RR 0.75, 95% CI 0.53 to 1.07; low quality evidence). However, there was
      moderate quality evidence that the use of VTV modes resulted in a reduction in
      the primary outcome, death or BPD at 36 weeks' gestation (typical RR 0.73, 95% CI
      0.59 to 0.89; typical NNTB 8, 95% CI 5 to 20) and the following secondary
      outcomes: rates of pneumothorax (typical RR 0.52, 95% CI 0.31 to 0.87; typical
      NNTB 20, 95% CI 11 to 100), mean days of mechanical ventilation (MD -1.35 days,
      95% CI -1.83 to -0.86), rates of hypocarbia (typical RR 0.49, 95% CI 0.33 to
      0.72; typical NNTB 3, 95% CI 2 to 5), rates of grade 3 or 4 intraventricular
      haemorrhage (typical RR 0.53, 95% CI 0.37 to 0.77; typical NNTB 11, 95% CI 7 to
      25) and the combined outcome of periventricular leukomalacia with or without
      grade 3 or 4 intraventricular haemorrhage (typical RR 0.47, 95% CI 0.27 to 0.80;
      typical NNTB 11, 95% CI 7 to 33). VTV modes were not associated with any
      increased adverse outcomes. AUTHORS' CONCLUSIONS: Infants ventilated using VTV
      modes had reduced rates of death or BPD, pneumothoraces, hypocarbia, severe
      cranial ultrasound pathologies and duration of ventilation compared with infants
      ventilated using PLV modes. Further studies are needed to identify whether VTV
      modes improve neurodevelopmental outcomes and to compare and refine VTV
      strategies.

PMID- 29039885
TI  - Attitudes and Practices Among Medical Providers Regarding Oral Health Assessments
      in Young Children.
AB  - Research indicates that while most nondental medical providersbelieve pediatric
      oral assessments are important, most lack education and training.This study
      investigated a metropolitan area in Southern California medicalproviders'
      knowledge, attitudes and practices on oral health assessments. Resultsindicate a
      high incidence of incorrect dental knowledge. Common barriers werelack of
      knowledge and time. Early intervention and timely dental referrals amongnondental
      medical providers can play a significant role in promoting oral health.

PMID- 29039886
TI  - Corrigendum to "Transdermal alcohol concentration data collected during a
      contingency management program to reduce at-risk drinking"

PMID- 29039887
TI  - Taking Inventory to Safeguard Your Practice.

PMID- 29039888
TI  - Which is best method for instillation of topical therapy to the upper urinary
      tract? An in vivo porcine study to evaluate three delivery methods.
AB  - PURPOSE: To compare the staining intensity of the upper urinary tract (UUT)
      urothelium among three UUT delivery methods in an in vivo porcine model.
      MATERIALS AND METHODS: A fluorescent dye solution (indigo carmine) was delivered
      to the UUT via three different methods: antegrade perfusion, vesico-ureteral
      reflux via indwelling ureteric stent and retrograde perfusion via a 5F open-ended
      ureteral catheter. Twelve renal units were tested with 4 in each method. After a
      2-hour delivery time, the renal-ureter units were harvested en bloc. Time from
      harvesting to analysis was also standardised to be 2 hours in each arm. Three
      urothelium samples of the same weight and size were taken from each of the 6 pre
      defined points (upper pole, mid pole, lower pole, renal pelvis, mid ureter and
      distal ureter) and the amount of fluorescence was measured with a spectrometer.
      RESULTS: The mean fluorescence detected at all 6 predefined points of the UUT
      urothelium was the highest for the retrograde method. This was statistically
      significant with p-value less than <0.05 at all 6 points. CONCLUSIONS: Retrograde
      infusion of UUT by an open ended ureteral catheter resulted in highest mean
      fluorescence detected at all 6 pre-defined points of the UUT urothelium compared
      to antegrade infusion and vesico-ureteral reflux via indwelling ureteric stents
      indicating retrograde method ideal for topical therapy throughout the UUT
      urothelium. More clinical studies are needed to demonstrate if retrograde method
      could lead to better clinical outcomes compared to the other two methods.

PMID- 29039889
TI  - Robot-assisted single port radical nephrectomy and cholecystectomy: description
      and technical aspects.
AB  - INTRODUCTION: Robot-Assisted Single Site Radical Nephrectomy (RASS-RN) has been
      reported by surgeons in Europe and United States (1-3). To our best knowledge
      this video presents the first RASS-RN with concomitant cholecystectomy performed
      in Latin America. CASE: A 66 year-old renal transplant male due to chronic renal
      failure presented with an incidental 1.3cm nodule in the upper pole of the right
      kidney. In addition, symptomatic gallbladder stones were detected. RESULTS:
      Patient was placed in modified flank position. Multichannel single port device
      was placed using Hassan's technique through a 3cm supra-umbilical incision.
      Standard radical nephrectomy and cholecystectomy were made using na 8.5mm camera,
      two 5mm robotic arms and an assistant 5mm access. Surgery time and estimated
      blood loss were 208 minutes and 100mL, respectively. Patient did well and was
      discharged within less than 48 hours, without complications. Pathology report
      showed benign renomedullary tumor of interstitial cells and chronic
      cholecystitis. DISCUSSION: Robotic technology improves ergonomics, gives better
      precision and enhances ability to approach complex surgeries. Robot-assisted
      Single Port aims to reduce the morbidity of multiple trocar placements while
      maintaining the advantages of robotic surgery (2). Limitations include the use of
      semi-rigid instruments providing less degree of motion and limited space leading
      to crash between instruments. On the other hand, it is possible to perform
      complex and concomitant surgeries with just one incision. CONCLUSION: RASS-RN
      seems to be safe and feasible option for selected cases. Studies should be
      performed to better understand the results using single port technique in
      Urology.

PMID- 29039890
TI  - Robot-assisted laparoscopic bladder diverticulectomy and greenlight laser
      anatomic vaporization of the prostate.

PMID- 29039891
TI  - Laparoscopic - assisted percutaneous nephrolithotomy as an alternative in the
      treatment of complex renal calculi in patients with retrorenal colon.

PMID- 29039872
TI  - Vitamin D Use and Health Outcomes After Surgery for Hip Fracture.
AB  - Daily administration of vitamin D is important for maintaining bone homeostasis.
      The orthopedic community has shown increased interest in vitamin D
      supplementation and patient outcomes after fracture. The current study used data
      from a large hip fracture trial to determine the proportion of patients who
      consistently used vitamin D after hip fracture surgery and to determine whether
      supplementation was associated with improved health-related quality of life and
      reduced reoperation rates. The FAITH study is a multicenter trial of elderly
      patients with femoral neck fracture treated with internal fixation. The current
      study asked a subset of patients included in the FAITH study about vitamin D
      supplementation and categorized them as consistent users, inconsistent users, or
      nonusers. This study also evaluated whether supplementation was associated with
      improved quality of life and reduced reoperation rates. The final analysis
      included 573 patients (mean age, 74.1 years; female, 66.3%; nondis-placed
      fractures, 72.4%). A total of 18.7% of participants reported no use of vitamin D,
      35.6% reported inconsistent use, and 45.7% reported consistent use. Adjusted
      analysis found that consistent supplementation was associated with a 2.42
      increase of the Short Form-12 physical component score 12 months postoperatively
      (P=.033). However, supplementation was not associated with reduced reoperation
      rates (P=.386). Despite guidelines recommending vitamin D supplementation, a low
      proportion of elderly patients with hip fracture use vitamin D consistently,
      suggesting a need for additional strategies to promote compliance. This study
      found that the use of vitamin D was associated with a statistically significant
      but not clinically significant improvement in health-related quality of life
      after hip fracture. Further research is needed to confirm these findings.
      [Orthopedics. 2017; 40(5):e868-e875.].

PMID- 29039892
TI  - Step by step male to female transsexual surgery.
AB  - INTRODUCTION: After the diagnosis of transsexualism is confirmed therapy
      commences with psychotherapeutic preparation for the conversion, and after
      conversion, long-term patient rehabilitation is maintained for at least two
      years. The indication for surgery is chronic discomfort caused by discord with
      the patient's natural gender, intense dislike of developing secondary sex
      characteristics and the onset of puberty. The surgical conversion of transsexuals
      is the main step in the complex care of these problematic patients (1). This
      surgery was first described by Benjamin H, using a flap of inverted penile skin
      (2) and is considered the gold standard since then. Male-to-female transsexual
      surgical techniques are well defined and give good cosmetic and functional
      results. Sex reassignment surgery promotes the improvement of psychological
      aspects and social relationships as shown in the World Health Organization
      Quality of Life Assessment applied in the patients submitted to this procedure
      (3). Techniques include the creation of a normal appearing female introitus, a
      vaginoplasty allowing sexual intercourse and the capability of clitoral orgasm
      (4). Various methods for neovaginoplasty have been described and can be
      classified into five categories, i.e. pedicled intestinal transplants, penile
      skin grafts, penile skin flaps, non-genital skin flaps and non-genital skin
      grafts (5). In our Hospital, we use penile and scrotal skin flaps. Until now, 174
      procedures have been performed by our team using this technique with high rates
      of satisfaction (3). PATIENTS AND METHODS: We present a step-by-step male to
      female transsexual surgery. CONCLUSION: Surgical gender reassignment of male
      transsexuals resulted in replicas of female genitalia which enabled coitus with
      orgasm (1). With this video we show step by step that a surgery using penile skin
      flaps is able to be performed with good cosmetic results.

PMID- 29039893
TI  - Open radical prostatectomy reproducing robot-assisted radical prostatectomy:
      Involving antegrade nerve sparing and continuous anastomosis.
AB  - PURPOSE: To present modified RRP using the same method as RALP and compare its
      surgical outcomes with RALP. MATERIALS AND METHODS: Demographics, perioperative
      and functional outcomes of the 322 patients that underwent RRP (N=99) or RALP
      (N=223) at our institution from January 2011 through June 2013 were evaluated
      retrospectively. Postoperative incontinence and erectile dysfunction are involved
      functional outcomes. During the modified procedure, the bladder neck was
      dissected first as for RALP. After dissection of vas deference and seminal
      vesicle, the prostate was dissected in an antegrade fashion with bilateral nerve
      saving. Finally, the urethra was cut at the prostate apex. After a Rocco suture
      was applied, and then urethrovesical anastomosis was performed with continuous
      suture as for RALP. RESULTS: Perioperative characteristics and complication rates
      were similar in the RRP and RALP groups except for mean estimated blood loss
      (p<0.001) and operative time (p<0.001). Incontinence rates at 3 and 12 months
      after RRP decreased from 67.6% to 10.1 and after RALP decreased from 53.4% to
      5.4%. Positive surgical margin rates were non-significantly different in the RRP
      and RALP groups (30.3% and 37.2%, respectively). Overall postoperative potency
      rate at 12 months was not significant different in RRP and RALP groups (34.3% and
      43.0%). CONCLUSIONS: RRP reproducing RALP was found to have surgical outcomes
      comparable to RALP. This technique might be adopted by experienced urologic
      surgeons as a standard procedure.

PMID- 29039894
TI  - Ureteral orifice involvement by urothelial carcinoma: long term oncologic and
      functional outcomes.
AB  - PURPOSE: Bladder cancer (BC) may involve the ureteral orifice, and the resection
      of the orifice has oncological and functional consequences such as development of
      upper tract urothelial carcinoma (UTUC), vesicoureteral reflux or ureteral
      stenosis. The aim of this study was to investigate the oncological and functional
      outcomes of the ureteral orifice resection in BC patients and determine the
      predictive factors for UTUC development. MATERIALS AND METHODS: A total of 1359
      patients diagnosed with BC, between 1992 and 2012, were reviewed retrospectively.
      Patients were grouped with respect to orifice resection and compared for
      development of UTUC, survival and functional outcomes. Kaplan-Meier method was
      used to compare survival outcomes. Logistic regression analysis was performed to
      determine predictors of UTUC development. RESULTS: Ureteral orifice involvement
      was detected in 138 (10.2%) patients. The rate of synchronous (10.1% vs. 0.7%,
      p=0.0001) and metachronous (5.3% vs. 0.9%, p=0.0001) UTUC development was found
      to be higher in patients with ureteral orifice involvement. Orifice involvement
      and tumor stage were found to be associated with development of UTUC in the
      regression analysis. Overall (p=0.963) and cancer specific survival rates
      (p=0.629) were found to be similar. Hydronephrosis was also significantly higher
      in patients with orifice involved BC, due to the orifice obstruction caused by
      the tumor (33.3% vs. 13.9%, p<0.05). CONCLUSIONS: BC with ureteral orifice
      involvement has significantly increased the risk of having synchronous or
      metachronous UTUC. However, orifice involvement was not found to be associated
      with survival outcomes. Development of stricture due to resection is a very rare
      complication.

PMID- 29039895
TI  - Effects of Copaiba oil in the healing process of urinary bladder in rats.
AB  - INTRODUCTION: The appropriate closure of the urinary bladder is important to many
      urologic procedures to avoid the formation of fistulas and strictures by
      excessive fibrosis. This paper presents the alterations in the bladder healing
      process of rats after the topical use of Copaiba oil (Copaifera reticulata).
      MATERIAL AND METHODS: Ten male Wistar rats were used and randomly divided into
      two groups: Control group (CG): injected 1ml/kg of saline solution on the suture
      line; and Copaiba group (CpG): 0.63ml/kg of copaiba oil applied to the suture
      line. Euthanasia was performed on the seventh day after surgery. The criteria
      observed were adherences formation, histopathological modifications and
      stereology for collagen. RESULTS: Both groups showed adhesions to the bladder,
      with no statistically significant difference (p=0.1481). The microscopic
      evaluation revealed a trend to more severe acute inflammation process on the CpG,
      but there was statistical difference only in the giant cells reaction (p=0.0472)
      and vascular proliferation (p=0.0472). The stereology showed no difference.
      CONCLUSION: The copaiba oil modified the healing process, improving the quantity
      of giant cells and vascular proliferation, but not interfered in the collagen
      physiology.

PMID- 29039896
TI  - Transition to adulthood with a bladder augmentation: histopathologic concerns.
AB  - AIM: To investigate the histopathologic changes in native bladder and
      gastrointestinal segment, the relation between histopathologic changes, type of
      operation and the period passed over operation in patients with bladder
      augmentation. MATERIALS AND METHODS: Twenty consecutive patients were enrolled in
      this study. Histopathologic evaluation of the cystoscopic mucosal biopsies from
      native bladder and enteric augment was performed in all patients. RESULTS: Active
      or chronic non-specific inflammation of various degrees was found in all
      specimens except two. Metaplastic changes were detected in 3 patients. Two
      patients had squamous metaplasia (one focal, one extensive) and one patient had
      intestinal metaplasia. All metaplastic changes were found in native bladder
      specimens. The type of augmentation in patients with metaplastic changes were
      ileocystoplasty and sigmoidocystoplasty. No signs of malignancy were detected in
      any patient. CONCLUSION: The complexity of the disorders requiring bladder
      augmentation does not let the surgeons to draw a clear line between different
      groups of complications including malignancy formation. However, due to
      challenging course of the augmentation procedure itself, surgeons should be well
      aware of the possibility of malignancy development.

PMID- 29039898
TI  - Risk Factors for Aneurysm Recurrence: Response

PMID- 29039897
TI  - Biochemical recurrence after radical prostatectomy: what does it mean?
AB  - BACKGROUND: Radical prostatectomy (RP) has been used as the main primary
      treatment for prostate cancer (PCa) for many years with excellent oncologic
      results. However, approximately 20-40% of those patients has failed to RP and
      presented biochemical recurrence (BCR). Prostatic specific antigen (PSA) has been
      the pivotal tool for recurrence diagnosis, but there is no consensus about the
      best PSA threshold to define BCR until this moment. The natural history of BCR
      after surgical procedure is highly variable, but it is important to distinguish
      biochemical and clinical recurrence and to find the correct timing to start
      multimodal treatment strategy. Also, it is important to understand the role of
      each clinical and pathological feature of prostate cancer in BCR, progression to
      metastatic disease and cancer specific mortality (CSM). Review design: A simple
      review was made in Medline for articles written in English language about
      biochemical recurrence after radical prostatectomy. OBJECTIVE: To provide an
      updated assessment of BCR definition, its meaning, PCa natural history after BCR
      and the weight of each clinical/pathological feature and risk group
      classifications in BCR, metastatic disease and CSM.

PMID- 29039900
TI  - Lessons Learned From HIPAA Enforcement.

PMID- 29039901
TI  - Tech Trends. A look into the latest dental and general technology on the market.

PMID- 29039902
TI  - Calculated decisions: Emergency Department Assessment of Chest Pain Score (EDACS)

PMID- 29039903
TI  - Calculated decisions: HEART Score for major cardiac events

PMID- 29039904
TI  - Calculated decisions: TIMI risk score for UA/NSTEMI

PMID- 29039905
TI  - Calculated decisions: Vancouver Chest Pain Rule

PMID- 29039906
TI  - Few-Layer MXenes Delaminated via High-Energy Mechanical Milling for Enhanced
      Sodium-Ion Batteries Performance.
AB  - The global availability of sodium makes the exploration of superior sodium-ion
      batteries attractive for energy storage application. MXenes, as one of the most
      promising anodes for sodium-ion batteries, have been reported to have many
      advantages, such as high electronic conductivity and a hydrophilic surface.
      However, the compact multilayer structure and deficient delamination
      significantly inhibits their application, requiring high energy and showing
      decreased storage capacity and poor rate capabilities. Few-layer MXene has been
      proved to benefit superior electrochemical properties with a better ionic
      conductivity and two-dimensional layer structure. Herein, we report scale
      delamination of few-layer MXene nanosheets as anodes for sodium-ion batteries,
      which are prepared via an organic solvent assist high-energy mechanical-milling
      method. This approach efficiently prevents the oxidation of MXene and produces
      few-layer nanosheets structure, facilitating fast electron transport and Na+
      diffusion. Electrochemical tests demonstrate that the few-layer MXenes show high
      specific capacity, excellent cycle stability, and good rate performance.
      Specifically, few-layer MXene nanosheets deliver a high reversible capacity of
      267 mA h g-1 at a current density of 0.1 A g-1. After cycling 1500 cycles at a
      high rate of 1 A g-1, a reversible capacity of 76 mA h g-1 could be maintained.

PMID- 29039907
TI  - Li+-Permeable Film on Lithium Anode for Lithium Sulfur Battery.
AB  - Lithium-sulfur (Li-S) battery is an important candidate for next-generation
      energy storage. However, the reaction between polysulfide and lithium (Li) anode
      brings poor cycling stability, low Coulombic efficiency, and Li corrosion.
      Herein, we report a Li protection technology. Li metal was treated in crown ether
      containing electrolyte, and thus, treated Li was further used as the anode in Li
      S cell. Due to the coordination between Li+ and crown ether, a Li+-permeable film
      can be formed on Li, and the film is proved to be able to block the detrimental
      reaction between Li anode and polysulfide. By using the Li anode pretreated in 2
      wt % B15C5-containing electrolyte, Li-S cell exhibits significantly improved
      cycling stability, such as~900 mAh g-1 after 100 cycles, and high Coulombic
      efficiency of>93%. In addition, such effect is also notable when high S loading
      condition is applied.

PMID- 29039908
TI  - A Comprehensive High-Resolution Targeted Workflow for the Deep Profiling of
      Sphingolipids.
AB  - Sphingolipids make up a highly diverse group of biomolecules that not only are
      membrane components but also are involved in various cellular functions such as
      signaling and protein sorting. To obtain a quantitative view of the
      sphingolipidome, sensitive, accurate, and comprehensive methods are needed. Here,
      we present a targeted reversed-phase liquid chromatography-high-resolution mass
      spectrometry-based workflow that significantly increases the accuracy of measured
      sphingolipids by resolving nearly isobaric and isobaric species; this is
      accomplished by a use of (i) an optimized extraction procedure, (ii) a segmented
      gradient, and (iii) parallel reaction monitoring of a sphingolipid specific
      fragmentation pattern. The workflow was benchmarked against an accepted
      sphingolipid model system, the RAW 264.7 cell line, and 61 sphingolipids were
      quantified over a dynamic range of 7 orders of magnitude, with detection limits
      in the low femtomole per milligram of protein level, making this workflow an
      extremely versatile tool for high-throughput sphingolipidomics.

PMID- 29039909
TI  - Indocyanine Green-holo-Transferrin Nanoassemblies for Tumor-Targeted Dual-Modal
      Imaging and Photothermal Therapy of Glioma.
AB  - Active-targeted cancer imaging and therapy of glioma has attracted much attention
      in theranostic nanomedicine. As a promising tumor-targeting ligand, holo
      transferrin (holo-Tf) has been applied for enhancing delivery of
      nanotheranostics. However, holo-Tf-based nanoassemblies for active targeting
      mediated multimodal imaging and therapeutics have not been previously reported.
      Here, we develop a one-step method for the preparation of holo-Tf-indocyanine
      green (holo-Tf-ICG) nanoassemblies for fluorescence (FL) and photoacoustic (PA)
      dual-modal imaging and photothermal therapy (PTT) of glioma. The nanoassemblies
      are formed by hydrophobic interaction and hydrogen bonds between holo-Tf and ICG,
      which exhibit excellent active tumor-targeting and high biocompability. The brain
      tumor with highly expressed Tf receptor can be clearly observed with holo-Tf-ICG
      nanoassemblies base on FL and PA dual-modal imaging in subcutaneous and
      orthotopic glioma models. Under the near-infrared laser irradiation, the holo-Tf
      ICG nanoassemblies accumulated in tumor regions can efficiently convert laser
      energy into hyperthermia for tumor ablation. The novel theranostic nanoplatform
      holds great promise for precision diagnosis and treatment of glioma.

PMID- 29039910
TI  - Sequential Dihydrogen Desorption from Hydride-Protected Atomically Precise Silver
      Clusters and the Formation of Naked Clusters in the Gas Phase.
AB  - We report the formation of naked cluster ions of silver of specific nuclearities,
      uncontaminated by other cluster ions, derived from monolayer-protected clusters.
      The hydride and phosphine co-protected cluster, [Ag18(TPP)10H16]2+ (TPP,
      triphenylphosphine), upon activation produces the naked cluster ion, Ag17+,
      exclusively. The number of metal atoms present in the naked cluster is almost the
      same as that in the parent material. Two more naked cluster ions, Ag21+ and
      Ag19+, were also formed starting from two other protected clusters,
      [Ag25(DPPE)8H22]3+ and [Ag22(DPPE)8H19]3+, respectively (DPPE, 1,2
      bis(diphenylphosphino)ethane). By systematic fragmentation, naked clusters of
      varying nuclei are produced from Ag17+ to Ag1+ selectively, with systematic
      absence of Ag10+, Ag6+, and Ag4+. A seemingly odd number of cluster ions are
      preferred due to the stability of the closed electronic shells. Sequential
      desorption of dihydrogen occurs from the cluster ion, Ag17H14+, during the
      formation of Agn+. A comparison of the pathways in the formation of similar naked
      cluster ions starting from two differently ligated clusters has been presented.
      This approach developed bridges the usually distinct fields of gas-phase metal
      cluster chemistry and solution-phase metal cluster chemistry. We hope that our
      findings will enrich nanoscience and nanotechnology beyond the field of clusters.

PMID- 29039911
TI  - Halide Re-Shelled Quantum Dot Inks for Infrared Photovoltaics.
AB  - Colloidal quantum dots are promising materials for tandem solar cells that
      complement silicon and perovskites. These devices are fabricated from solution
      phase; however, existing methods for making infrared-bandgap CQD inks suffer
      agglomeration and fusion during solution exchange. Here we develop a ligand
      exchange that provides robust surface protection and thereby avoids aggregation.
      First, we exchanged long oleic acid ligands to a mixed system comprising medium
      chain ammonium and anionic chloride ligands; we then reshelled the surface using
      short halides and pseudohalide ligands that enabled transfer to a polar solvent.
      Absorbance and photoluminescence measurements reveal the retention of exciton
      sharpness, whereas X-ray photoelectron spectroscopy indicates halide capping. The
      best power conversion efficiency of these devices is 0.76 power points after
      filtering through silicon, which is 1.9* higher than previous single-step
      solution-processed IR-CQD solar cells.

PMID- 29039912
TI  - 3D-Printed Paper Spray Ionization Cartridge with Integrated Desolvation Feature
      and Ion Optics.
AB  - In this work we present the application of 3D-printing for the miniaturization
      and functionalization of an ion source for (portable) mass spectrometry (MS). Two
      versions of a 3D-printed cartridge for paper spray ionization (PSI) are
      demonstrated, assessed, and compared. We first focus on the use of 3D-printing to
      enable the integration of an embedded electrostatic lens and a manifold for
      internal sheath gas distribution and delivery. Cartridges with and without a
      sheath gas manifold and an electrostatic lens are compared with respect to
      analytical performance and operational flexibility. The sensitivity and limit of
      detection are improved in the cartridge with an electrostatic lens and sheath gas
      manifold compared to the cartridge without (15% and over 6.5* smaller,
      respectively). The use of these focusing elements also improved the average spray
      stability. Furthermore, the range of potentials required for PSI was lower, and
      the distance to the MS orifice over which spray could be obtained was larger.
      Importantly, both setups allowed quantification of a model drug in the ng/mL
      range with single-stage MS, after correction for spray instability. Finally, we
      believe that this work is an example of the impact that 3D-printing will have on
      the future of analytical device fabrication, miniaturization, and
      functionalization.

PMID- 29039913
TI  - Low-Temperature One-Step Growth of AlON Thin Films with Homogenous Nitrogen
      Doping Profile by Plasma-Enhanced Atomic Layer Deposition.
AB  - The AlON film with homogeneous nitrogen-doping profile was grown by plasma
      enhanced atomic layer deposition (PEALD) at low temperature. In this work, the
      precursors of the NH3 and the O2 were simultaneously introduced into the chamber
      during the PEALD growth at a relatively low temperature of 185  degrees C. It is
      found that the composition of the obtained film quickly changes from AlN to Al2O3
      when a small amount of O2 is added. Thus, the NH3:O2 ratio should be maintained
      at a relatively high level (>85%) for realizing the AlON growth. Benefited from
      the growth method, the nitrogen can be doped evenly in the entire film. Moreover,
      the AlON films exhibit a lower surface roughness than the AlN as well as the
      Al2O3 ones. The Al 2p and N 1s X-ray photoelectron spectra show that the AlON
      film is composed of Al-N, Al-O, and N-Al-O bonds. Moreover, a three-layer
      construction of the AlON film is proposed through the Si 2p spectra analysis and
      reconfirmed by the transmission electron microscopy characterization. At last,
      the electrical and optical tests indicate that the AlON films prepared in this
      work can be employed as the gate dielectric in transistor application as well as
      the antireflection layer in photovoltaic application.

PMID- 29039914
TI  - Rapid Adsorption Enables Interface Engineering of PdMnCo Alloy/Nitrogen-Doped
      Carbon as Highly Efficient Electrocatalysts for Hydrogen Evolution Reaction.
AB  - The catalytic performance of Pd-based catalysts has long been hindered by surface
      contamination, particle agglomeration, and lack of rational structural design.
      Here we report a simple adsorption method for rapid synthesis (~90 s) of
      structure-optimized Pd alloy supported on nitrogen-doped carbon without the use
      of surfactants or extra reducing agents. The material shows much lower
      overpotential than 30 wt % Pd/C and 40 wt % Pt/C catalysts while exhibiting
      excellent durability (80 h). Moreover, unveiled by the density functional theory
      (DFT) calculation results, the underlying reason for the outstanding performance
      is that the PdMnCo alloy/pyridinic nitrogen-doped carbon interfaces weaken the
      hydrogen-adsorption energy on the catalyst and thus optimize the Gibbs free
      energy of the intermediate state (DeltaGH*), leading to a remarkable
      electrocatalytic activity. This work also opens up an avenue for quick synthesis
      of a highly efficient structure-optimized Pd-based catalyst.

PMID- 29039915
TI  - Two-Dimensional Vanadium Carbide (MXene) as a High-Capacity Cathode Material for
      Rechargeable Aluminum Batteries.
AB  - Rechargeable aluminum batteries (Al batteries) can potentially be safer, cheaper,
      and deliver higher energy densities than those of commercial Li-ion batteries
      (LIBs). However, due to the very high charge density of Al3+ cations and their
      strong interactions with the host lattice, very few cathode materials are known
      to be able to reversibly intercalate these ions. Herein, a rechargeable Al
      battery based on a two-dimensional (2D) vanadium carbide (V2CTx) MXene cathode is
      reported. The reversible intercalation of Al3+ cations between the MXene layers
      is suggested to be the mechanism for charge storage. It was found that the
      electrochemical performance could be significantly improved by converting
      multilayered V2CTx particles to few-layer sheets. With specific capacities of
      more than 300 mAh g-1 at high discharge rates and relatively high discharge
      potentials, V2CTx MXene electrodes show one of the best performances among the
      reported cathode materials for Al batteries. This study can lead to foundations
      for the development of high-capacity and high energy density rechargeable Al
      batteries by showcasing the potential of a large family of intercalation-type
      cathode materials based on MXenes.

PMID- 29039916
TI  - Hybrid Nanocomposite Films Comprising Dispersed VO2 Nanocrystals: A Scalable
      Aqueous-Phase Route to Thermochromic Fenestration.
AB  - Buildings consume an inordinate amount of energy, accounting for 30-40% of
      worldwide energy consumption. A major portion of solar radiation is transmitted
      directly to building interiors through windows, skylights, and glazed doors where
      the resulting solar heat gain necessitates increased use of air conditioning.
      Current technologies aimed at addressing this problem suffer from major
      drawbacks, including a reduction in the transmission of visible light, thereby
      resulting in increased use of artificial lighting. Since currently used coatings
      are temperature-invariant in terms of their solar heat gain modulation, they are
      unable to offset cold-weather heating costs that would otherwise have resulted
      from solar heat gain. There is considerable interest in the development of
      plastic fenestration elements that can dynamically modulate solar heat gain based
      on the external climate and are retrofittable onto existing structures. The metal
      insulator transition of VO2 is accompanied by a pronounced modulation of near
      infrared transmittance as a function of temperature and can potentially be
      harnessed for this purpose. Here, we demonstrate that a nanocomposite thin film
      embedded with well dispersed sub-100-nm diameter VO2 nanocrystals exhibits a
      combination of high visible light transmittance, effective near-infrared
      suppression, and onset of NIR modulation at wavelengths <800 nm. In our approach,
      hydrothermally grown VO2 nanocrystals with <100 nm diameters are dispersed within
      a methacrylic acid/ethyl acrylate copolymer after either (i) grafting of silanes
      to constitute an amorphous SiO2 shell or (ii) surface functionalization with
      perfluorinated silanes and the use of a perfluorooctanesulfonate surfactant.
      Homogeneous and high optical quality thin films are cast from aqueous dispersions
      of the pH-sensitive nanocomposites onto glass. An entirely aqueous-phase process
      for preparation of nanocrystals and their effective dispersion within polymeric
      nanocomposites allows for realization of scalable and viable plastic fenestration
      elements.

PMID- 29039917
TI  - Multifunctional Theranostic Nanoparticles Based on Exceedingly Small Magnetic
      Iron Oxide Nanoparticles for T1-Weighted Magnetic Resonance Imaging and
      Chemotherapy.
AB  - The recently emerged exceedingly small magnetic iron oxide nanoparticles (ES
      MIONs) (<5 nm) are promising T1-weighted contrast agents for magnetic resonance
      imaging (MRI) due to their good biocompatibility compared with Gd-chelates.
      However, the best particle size of ES-MIONs for T1 imaging is still unknown
      because the synthesis of ES-MIONs with precise size control to clarify the
      relationship between the r1 (or r2/r1) and the particle size remains a challenge.
      In this study, we synthesized ES-MIONs with seven different sizes below 5 nm and
      found that 3.6 nm is the best particle size for ES-MIONs to be utilized as T1
      weighted MR contrast agent. To enhance tumor targetability of theranostic
      nanoparticles and reduce the nonspecific uptake of nanoparticles by normal
      healthy cells, we constructed a drug delivery system based on the 3.6 nm ES-MIONs
      for T1-weighted tumor imaging and chemotherapy. The laser scanning confocal
      microscopy (LSCM) and flow cytometry analysis results demonstrate that our
      strategy of precise targeting via exposure or hiding of the targeting ligand RGD2
      on demand is feasible. The MR imaging and chemotherapy results on the cancer
      cells and tumor-bearing mice reinforce that our DOX@ES-MION3@RGD2@mPEG3
      nanoparticles are promising for high-resolution T1-weighted MR imaging and
      precise chemotherapy of tumors.

PMID- 29039918
TI  - Bioinspired Antioxidant Defense System Constructed by Antioxidants-Eluting
      Electrospun F127-Based Fibers.
AB  - Cells were continuously exposed to oxidative damage by overproduction of reactive
      oxygen species (ROS) when they contacted implanted biomaterials. The strategy to
      prevent cells from oxidative injures remains a challenge. Inspired by the
      antioxidant defense system of cells, we constructed a biocompatible and ROS
      responsive architecture on the substrate of styrene-b-(ethylene-co-butylene)-b
      styrene elastomer (SEBS). The strategy was based on fabrication of architectures
      through reactive electrospinning of mixture including SEBS, acylated Pluronic
      F127, copolymer of poly(ethylene glycol) diacrylate and 1,2-ethanedithiol (PEGDA
      EDT), and antioxidants (AA-2G) and ROS-triggered release of AA-2G from
      microfibers to detoxify the excess ROS. We demonstrated that the stable and
      hydrophilic architecture was constructed by phase separation of SEBS/F127
      components and cross-linking between polymer chains during electrospinning; the
      ROS-responsive fibers controlled the release of AA-2G and the interaction of AA
      2G with ROS reduced the oxidative damage to cells. The bioinspired architecture
      not only reduced mechanical and oxidative damage to cells but also maintained
      normal ROS level for physiological hemostasis. This work provides basic
      principles to design and develop antioxidative biomaterials for implantation in
      vivo.

PMID- 29039920
TI  - Shedding Light on the Photoisomerization Pathway of Donor-Acceptor Stenhouse
      Adducts.
AB  - Donor-acceptor Stenhouse adducts (DASAs) are negative photochromes that hold
      great promise for a variety of applications. Key to optimizing their switching
      properties is a detailed understanding of the photoswitching mechanism, which, as
      yet, is absent. Here we characterize the actinic step of DASA-photoswitching and
      its key intermediate, which was studied using a combination of ultrafast visible
      and IR pump-probe spectroscopies and TD-DFT calculations. Comparison of the time
      resolved IR spectra with DFT computations allowed to unambiguously identify the
      structure of the intermediate, confirming that light absorption induces a
      sequential reaction path in which a Z-E photoisomerization of C2-C3 is followed
      by a rotation around C3-C4 and a subsequent thermal cyclization step. First and
      second-generation DASAs share a common photoisomerization mechanism in
      chlorinated solvents with notable differences in kinetics and lifetimes of the
      excited states. The photogenerated intermediate of the second-generation DASA was
      photo-accumulated at low temperature and probed with time-resolved spectroscopy,
      demonstrating the photoreversibility of the isomerization process. Taken
      together, these results provide a detailed picture of the DASA isomerization
      pathway on a molecular level.

PMID- 29039921
TI  - Molecular Cobalt Catalysts for O2 Reduction: Low-Overpotential Production of H2O2
      and Comparison with Iron-Based Catalysts.
AB  - A series of mononuclear pseudomacrocyclic cobalt complexes have been investigated
      as catalysts for O2 reduction. Each of these complexes, with CoIII/II reduction
      potentials that span nearly 400 mV, mediate highly selective two-electron
      reduction of O2 to H2O2 (93-99%) using decamethylferrocene (Fc*) as the reductant
      and acetic acid as the proton source. Kinetic studies reveal that the rate
      exhibits a first-order dependence on [Co] and [AcOH], but no dependence on [O2]
      or [Fc*]. A linear correlation is observed between log(TOF) vs E1/2(CoIII/II) for
      the different cobalt complexes (TOF = turnover frequency). The thermodynamic
      potential for O2 reduction to H2O2 was estimated by measuring the H+/H2 open
      circuit potential under the reaction conditions. This value provides the basis
      for direct assessment of the thermodynamic efficiency of the different catalysts
      and shows that H2O2 is formed with overpotentials as low as 90 mV. These results
      are compared with a recently reported series of Fe-porphyrin complexes, which
      catalyze four-electron reduction of O2 to H2O. The data show that the TOFs of the
      Co complexes exhibit a shallower dependence on E1/2(MIII/II) than the Fe
      complexes. This behavior, which underlies the low overpotential, is rationalized
      on the basis of the catalytic rate law.

PMID- 29039919
TI  - The Molecular Tweezer CLR01 Stabilizes a Disordered Protein-Protein Interface.
AB  - Protein regions that are involved in protein-protein interactions (PPIs) very
      often display a high degree of intrinsic disorder, which is reduced during the
      recognition process. A prime example is binding of the rigid 14-3-3 adapter
      proteins to their numerous partner proteins, whose recognition motifs undergo an
      extensive disorder-to-order transition. In this context, it is highly desirable
      to control this entropy-costly process using tailored stabilizing agents. This
      study reveals how the molecular tweezer CLR01 tunes the 14-3-3/Cdc25CpS216
      protein-protein interaction. Protein crystallography, biophysical affinity
      determination and biomolecular simulations unanimously deliver a remarkable
      finding: a supramolecular "Janus" ligand can bind simultaneously to a flexible
      peptidic PPI recognition motif and to a well-structured adapter protein. This
      binding fills a gap in the protein-protein interface, "freezes" one of the
      conformational states of the intrinsically disordered Cdc25C protein partner and
      enhances the apparent affinity of the interaction. This is the first structural
      and functional proof of a supramolecular ligand targeting a PPI interface and
      stabilizing the binding of an intrinsically disordered recognition motif to a
      rigid partner protein.

PMID- 29039922
TI  - Synthesis and Crystal Structures of Volatile Neptunium(IV) beta-Diketonates.
AB  - Production of certified reference materials in support of domestic nuclear
      forensics programs require volatile precursors for introduction into
      electromagnetic isotopic separation instruments. beta-Diketone chelates of
      tetravalent actinides are known for their high volatility, but previously
      developed synthetic approaches require starting material (NpCl4) that is
      prohibitively difficult and hazardous to prepare. An alternative strategy was
      developed here that uses controlled potential electrolysis to reduce neptunium to
      the tetravalent state in submolar concentrations of hydrochloric acid. Four
      different beta-diketone ligands of varying degrees of fluorination were reacted
      with an aqueous solution of Np4+. Products of this reaction were characterized
      via X-ray diffraction and infrared spectroscopy, and were found to be neutral 8
      coordinate complexes that adopt square antiprismatic crystal geometry. Synthesis
      of Np beta-diketonates by this approach circumvents the necessity of using NpCl4
      in tetravalent Np coordination compound synthesis. The volatility of the
      complexes was assessed using thermogravimetric analysis, where the temperature of
      sublimation was determined to be in the range of 180 degrees  to 205  degrees C.
      The extent of fluorination did not appreciably alter the sublimation temperature
      of the complex. Thermal decomposition of these compounds was not observed during
      sublimation. High volatility and thermal stability of Np beta-diketonates make
      them ideal candidates for gaseous introduction into isotopic separation
      instruments.

PMID- 29039923
TI  - A Charge-Density-Tunable Three/Two-Dimensional Polymer/Graphene Oxide
      Heterogeneous Nanoporous Membrane for Ion Transport.
AB  - The design and fabrication of a robust nanoporous membrane in large scale is
      still a challenge and is of fundamental importance for practical applications.
      Here, a robust three/two-dimensional polymer/graphene oxide heterogeneous
      nanoporous membrane is constructed in large scale via the self-assembly approach
      by chemically designing a robust charge-density-tunable nanoporous ionomer with
      uniform pore size. To obtain a nanoporous polymer that maintains high mechanical
      strength and promotes multifunctionality, we designed a series of amphiphilic
      copolymers by introducing a positively charged pyridine moiety into the
      engineered polymer polyphenylsulfone. The multiphysical-chemical properties of
      the membrane enable it to work as a nanogate switch with synergy between
      wettability and surface charge change in response to pH. Then we systematically
      studied the transmembrane ionic transport properties of this two-/three
      dimensional porous system. By adjusting the charge density of the copolymer via
      chemical copolymerization through a controlled design route, the rectifying ratio
      of this asymmetric membrane could be amplified 4 times. Furthermore, we equipped
      a concentration-gradient-driven energy harvesting device with this charge-density
      tunable nanoporous membrane, and a maximum power of ~0.76 W m-2 was obtained. We
      expect this methodology for construction of a charge-density-tunable
      heterogeneous membrane by chemical design will shed light on the material design,
      and this membrane may further be used in energy devices, biosensors, and smart
      gating nanofluidic devices.

PMID- 29039924
TI  - Use of Electrochemistry in the Synthesis of Heterocyclic Structures.
AB  - The preparation and transformation of heterocyclic structures have always been of
      great interest in organic chemistry. Electrochemical technique provides a
      versatile and powerful approach to the assembly of various heterocyclic
      structures. In this review, we examine the advance in relation to the
      electrochemical construction of heterocyclic compounds published since 2000 via
      intra- and intermolecular cyclization reactions.

PMID- 29039925
TI  - Exosomes Secreted by HeLa Cells Shuttle on Their Surface the Plasma Membrane
      Associated Sialidase NEU3.
AB  - Sialidases are glycohydrolases that remove terminal sialic acid residues from
      oligosaccharides, glycolipids, and glycoproteins. The plasma membrane-associated
      sialidase NEU3 is involved in the fine-tuning of sialic acid-containing glycans
      directly on the cell surface and plays relevant roles in important biological
      phenomena such as cell differentiation, molecular recognition, and cancer
      transformation. Extracellular vesicles are membranous structures with a diameter
      of 0.03-1 MUm released by cells and can be detected in blood, urine, and culture
      media. Among extracellular vesicles, exosomes play roles in intercellular
      communication and maintenance of several physiological and pathological
      conditions, including cancer, and could represent a useful diagnostic tool for
      personalized nanomedicine approaches. Using inducible expression of the murine
      form of NEU3 in HeLa cells, a study of the association of the enzyme with
      exosomes released in the culture media has been performed. Briefly, NEU3 is
      associated with highly purified exosomes and localizes on the external leaflet of
      these nanovesicles, as demonstrated by enzyme activity measurements, Western blot
      analysis, and dot blot analysis using specific protein markers. On the basis of
      these results, it is plausible that NEU3 activity on exosome glycans enhances the
      dynamic biological behavior of these small extracellular vesicles by modifying
      the negative charge and steric hindrance of their glycocalyx. The presence of
      NEU3 on the exosomal surface could represent a useful marker for the detection of
      these nanovesicles and a tool for improving our understanding of the biology of
      these important extracellular carriers in physiological and pathological
      conditions.

PMID- 29039926
TI  - Zebrafish: A Visual Model To Evaluate the Biofate of Transferrin Receptor
      Targeted 7Peptide-Decorated Coumarin 6 Micelles.
AB  - In the present study, the zebrafish was explored as an in vivo model to assess
      the biofate of transferrin receptor (TfR)-targeted coumarin 6 (C6) micelles
      across various biological barriers. Three 7peptide (7pep)-decorated poly(ethylene
      glycol)-block-poly(epsilon-caprolactone) micelles loaded with fluorescence
      coumarin 6 (7pep-M-C6) with different ligand densities were constructed with
      particle sizes between 30 and 40 nm. Whole-mount immunostaining revealed that the
      expression level of TfR in the retina, brain, and intestine increased along with
      development stage. Compared to unmodified micelles, 7pep-M-C6 demonstrated higher
      uptake efficiency in the larval zebrafish. Preinhibition of TfR with 7pep
      implicated the TfR-mediated endocytosis pathway in the uptake of 7pep-M-C6.
      Confocal images of the larval zebrafish eye and brain showed the efficient
      delivery of C6 across the retinal pigment epithelial to the ganglion cell layer
      and the significant accumulation of C6 in all brain tissues, respectively, which
      plateaued when the ligand density was 10%. To investigate the intestinal
      distribution of C6, micelles were administered to adult zebrafish via gavaging.
      Notably, 7pep-M-C6 enhanced the transport of C6 across the villi and increased
      its aggregation into the basolateral membrane of the intestine. After the oral
      administration of 7pep-M-C6, C6 accumulated in the eye and brain. Forster
      resonance energy transfer analysis suggested that intact 7pep-modified micelles
      could enter the epithelial cells of the intestine, brain, and eye after oral
      administration in adult zebrafish. In conclusion, zebrafish could be used as a
      model for in vivo visual assessment of the biofate of TfR-targeted drug delivery
      systems.

PMID- 29039927
TI  - Packing Guidelines for Optimizing Singlet Fission Matrix Elements in Noncovalent
      Dimers.
AB  - A simplified version of the frontier orbital model for a noncovalent dimer is
      used to derive guidelines for dimer geometries that maximize the square of the
      electronic matrix element for singlet fission. The use of the guidelines requires
      only the knowledge of the highest occupied and lowest unoccupied orbital of the
      monomer and the overlaps of the atomic orbitals on partner A with those on
      partner B.

PMID- 29039928
TI  - Using Hyperfine Electron Paramagnetic Resonance Spectroscopy to Define the Proton
      Coupled Electron Transfer Reaction at Fe-S Cluster N2 in Respiratory Complex I.
AB  - Energy-transducing respiratory complex I (NADH:ubiquinone oxidoreductase) is one
      of the largest and most complicated enzymes in mammalian cells. Here, we used
      hyperfine electron paramagnetic resonance (EPR) spectroscopic methods, combined
      with site-directed mutagenesis, to determine the mechanism of a single proton
      coupled electron transfer reaction at one of eight iron-sulfur clusters in
      complex I, [4Fe-4S] cluster N2. N2 is the terminal cluster of the enzyme's
      intramolecular electron-transfer chain and the electron donor to ubiquinone.
      Because of its position and pH-dependent reduction potential, N2 has long been
      considered a candidate for the elusive "energy-coupling" site in complex I at
      which energy generated by the redox reaction is used to initiate proton
      translocation. Here, we used hyperfine sublevel correlation (HYSCORE)
      spectroscopy, including relaxation-filtered hyperfine and single-matched
      resonance transfer (SMART) HYSCORE, to detect two weakly coupled exchangeable
      protons near N2. We assign the larger coupling with A(1H) = [-3.0, -3.0, 8.7] MHz
      to the exchangeable proton of a conserved histidine and conclude that the
      histidine is hydrogen-bonded to N2, tuning its reduction potential. The histidine
      protonation state responds to the cluster oxidation state, but the two are not
      coupled sufficiently strongly to catalyze a stoichiometric and efficient energy
      transduction reaction. We thus exclude cluster N2, despite its proton-coupled
      electron transfer chemistry, as the energy-coupling site in complex I. Our work
      demonstrates the capability of pulse EPR methods for providing detailed
      information on the properties of individual protons in even the most challenging
      of energy-converting enzymes.

PMID- 29039930
TI  - Enantioselective Decarboxylative Cyanation Employing Cooperative Photoredox
      Catalysis and Copper Catalysis.
AB  - The merger of photoredox catalysis with asymmetric copper catalysis have been
      realized to convert achiral carboxylic acids into enantiomerically enriched alkyl
      nitriles. Under mild reaction conditions, the reaction exhibits broad substrate
      scope, high yields and high enantioselectivities. Furthermore, the reaction can
      be scaled up to synthesize key chiral intermediates to bioactive compounds.

PMID- 29039931
TI  - Profiling Cytidine Acetylation with Specific Affinity and Reactivity.
AB  - The human acetyltransferase NAT10 has recently been shown to catalyze formation
      of N4-acetylcytidine (ac4C), a minor nucleobase known to alter RNA structure and
      function. In order to better understand the role of RNA acetyltransferases in
      biology and disease, here we report the development and application of chemical
      methods to study ac4C. First, we demonstrate that ac4C can be conjugated to
      carrier proteins using optimized protocols. Next, we describe methods to access
      ac4C-containing RNAs, enabling the screening of anti-ac4C antibodies. Finally, we
      validate the specificity of an optimized ac4C affinity reagent in the context of
      cellular RNA by demonstrating its ability to accurately report on chemical
      deacetylation of ac4C. Overall, these studies provide a powerful new tool for
      studying ac4C in biological contexts, as well as new insights into the stability
      and half-life of this highly conserved RNA modification. More broadly, they
      demonstrate how chemical reactivity may be exploited to aid the development and
      validation of nucleobase-targeting affinity reagents designed to target the
      emerging epitranscriptome.

PMID- 29039929
TI  - Mechanistic Basis for ATP-Dependent Inhibition of Glutamine Synthetase by
      Tabtoxinine-beta-lactam.
AB  - Tabtoxinine-beta-lactam (TbetaL), also known as wildfire toxin, is a time- and
      ATP-dependent inhibitor of glutamine synthetase produced by plant pathogenic
      strains of Pseudomonas syringae. Here we demonstrate that recombinant glutamine
      synthetase from Escherichia coli phosphorylates the C3-hydroxyl group of the
      TbetaL 3-(S)-hydroxy-beta-lactam (3-HbetaL) warhead. Phosphorylation of TbetaL
      generates a stable, noncovalent enzyme-ADP-inhibitor complex that resembles the
      glutamine synthetase tetrahedral transition state. The TbetaL beta-lactam ring
      remains intact during enzyme inhibition, making TbetaL mechanistically distinct
      from traditional beta-lactam antibiotics such as penicillin. Our findings could
      enable the design of new 3-HbetaL transition state inhibitors targeting enzymes
      in the ATP-dependent carboxylate-amine ligase superfamily with broad therapeutic
      potential in many disease areas.

PMID- 29039933
TI  - Porous Uranium Diphosphonate Frameworks with Trinuclear Units Templated by
      Organic Ammonium Hydrolyzed from Amine Solvents.
AB  - By varying solvent systems, the solvothermal treatment of uranyl nitrate and
      methylenediphosphonic acid (H4PCP) afforded three new porous uranyl-organic
      frameworks (UOFs). All were structurally characterized by single-crystal X-ray
      diffraction and formulated as (Et2NH2)2[(UO2)3(PCP)2](H2O)2.5 (1),
      (MeNH3)(H3O)[(UO2)3(PCP)2(H2O)3] (2), and
      [Na(H2O)4](H3O)[(UO2)3(PCP)2(H2O)2](H2O)5 (3). These compounds crystallize with
      three-dimensional anionic frameworks containing U(VI) and distinct cationic
      species due to in situ solvent hydrolysis. The solvent systems diethylformamide
      (DEF), N-methyl-2-pyrrolindone (NMP), and the additive sodium vanadate (Na3VO4)
      significantly impact the resultant structures, affording diethyl ammonium, methyl
      ammonium, and sodium cations captured in channels of the anionic frameworks of 1
      3. In 1, a trinuclear U3O18 unit formed by three uranyl polyhedra that share
      edges is connected into a three-dimensional framework. Compound 2 has a three
      dimensional framework formed from a uranyl-methylenediphosphonate layer that is
      pillared by UO7 pentagonal bipyramids. With the inclusion of sodium cations, 3 is
      a porous framework containing UO7 pentagonal bipyramids within a layer, with
      sodium cations and UO6 square bipyramids linking the adjacent layers. Compounds 1
      3 feature the uranyl/ligand ratio of 3:2, but present diverse structural building
      units ranging from edge-shared trinuclear to heteronuclear assemblies. The
      compounds have been characterized by infrared (IR), Raman, and UV-vis
      spectroscopies, X-ray diffraction, and thermogravimetric analysis.

PMID- 29039932
TI  - Annotation: A Computational Solution for Streamlining Metabolomics Analysis.

PMID- 29039934
TI  - MeOTf-Mediated Annulation of Alkylnitriles and Arylalkynes Leading to
      Polysubstituted NH-Pyrroles.
AB  - A metal-free multicomponent domino reaction for the highly regioselective
      synthesis of tetrasubstituted NH-pyrroles from readily available alkylnitriles,
      arylalkynes, and MeOTf has been developed. A variety of NH-pyrroles were obtained
      in moderate to good yields under mild conditions. In addition, the reactions
      using diarylalkynes with electron-rich aryl groups were found to afford
      isoquinolines.

PMID- 29039935
TI  - Numerical Optimization of Density Functional Tight Binding Models: Application to
      Molecules Containing Carbon, Hydrogen, Nitrogen, and Oxygen.
AB  - New parametrizations for semiempirical density functional tight binding (DFTB)
      theory have been developed by the numerical optimization of adjustable parameters
      to minimize errors in the atomization energy and interatomic forces with respect
      to ab initio calculated data. Initial guesses for the radial dependences of the
      Slater-Koster bond integrals and overlap integrals were obtained from minimum
      basis density functional theory calculations. The radial dependences of the pair
      potentials and the bond and overlap integrals were represented by simple analytic
      functions. The adjustable parameters in these functions were optimized by
      simulated annealing and steepest descent algorithms to minimize the value of an
      objective function that quantifies the error between the DFTB model and ab initio
      calculated data. The accuracy and transferability of the resulting DFTB models
      for the C, H, N, and O system were assessed by comparing the predicted
      atomization energies and equilibrium molecular geometries of small molecules that
      were not included in the training data from DFTB to ab initio data. The DFTB
      models provide accurate predictions of the properties of hydrocarbons and more
      complex molecules containing C, H, N, and O.

PMID- 29039936
TI  - What Are the Physical Contents of Hubbard and Heisenberg Hamiltonian Interactions
      Extracted from Broken Symmetry DFT Calculations in Magnetic Compounds?
AB  - Analytical expressions of the interactions present in the Heisenberg-Dirac van
      Vleck and Hubbard Hamiltonians have been derived as functions of both the energy
      of several broken symmetry DFT solutions and their expectation value of the S2
      spin operator. Then, following a strategy of decomposition of the magnetic
      exchange coupling into its main contributions (direct exchange, kinetic exchange,
      and spin polarization) and using a recently proposed method of spin
      decontamination, values of these interactions have been extracted. As already
      observed, they weakly depend on the correlation functional but strongly depend on
      the exchange one. In order to distinguish between the effect of the
      delocalization of the magnetic orbitals and that of the amount of Hartree-Fock
      exchange (HFX) when hybrid exchange-correlation functionals are used, we have
      disentangled these two contributions by either freezing the magnetic orbitals and
      varying the amount of HFX or varying the magnetic orbitals while keeping the same
      amount of HFX. As expected, increasing the amount of HFX induces a slight
      relocalization of the magnetic orbitals on the magnetic center which results in a
      weak increase of the repulsion energy U parameter and a weak decrease of both the
      direct exchange Kab and hopping |t| parameters. Conversely, the amount of HFX has
      a huge effect on all the parameters, even when some of the parameters should be
      exchange-independent, like U. Indeed, it is analytically demonstrated that the
      physical content of the U parameter extracted from several broken-symmetry
      solutions depends on the amount of HFX and that this pathological behavior has
      the same origin as the self-interaction error. This result is interesting not
      only to theoretical chemists working in the field of magnetic systems but also to
      DFT methodologists interested in using this theory for studying either excited
      states or strongly correlated systems. Finally, the performance of the range
      separated omegaB97XD functional for both ferromagnetic and antiferromagnetic
      transition-metal compounds and organic systems must be noted.

PMID- 29039937
TI  - Concentration-Independent Stereodynamic g-Probe for Chiroptical Enantiomeric
      Excess Determination.
AB  - Enantiomeric excess (ee) determination is crucial in many aspects of science,
      from synthesis to materials. Within this subject, coupling molecular sensors with
      chiroptical techniques is a straightforward approach to the stereochemical
      analysis of chiral molecules, especially in terms of process immediacy and labor.
      Stereodynamic probes typically consist of racemic mixtures of rapidly
      interconverting enantiomeric conformers able to recognize a chiral analyte and
      greatly amplify its chiroptical readout. A great number of sensors have been
      developed, but their activity is generally restricted to one or a few classes of
      chemicals, and the analysis outcome relies on precise knowledge of the probe and
      analyte concentrations. This aspect in particular limits the potential practical
      applications. Here we report an oxo-vanadium(V) aminotriphenolate complex that
      was found to act as a concentration-independent stereodynamic sensor for a wide
      range of compounds. The bare complex is CD-silent, but coordination of an
      enantioenriched substrate immediately gives rise to intense Cotton effects in the
      visible region. Furthermore, a geometry change during the substrate-complex
      interaction leads to a marked optical response, as witnessed by a strong red
      shift of the probe absorption bands, thus allowing the generation of dichroic
      signals in an "interference-free" area of the spectrum. This peculiarity allows
      for a linear correlation at high wavelengths between the ee of the analyte and
      anisotropy g-factor. This parameter derives from the differential circularly
      polarized light absorption of the sample but is independent of concentration. The
      newly developed sensor based on a simple coordination process has an
      unprecedented general character in terms of substrate scope and employment.

PMID- 29039938
TI  - The Electro-Deposition/Dissolution of CuSO4 Aqueous Electrolyte Investigated by
      In Situ Soft X-ray Absorption Spectroscopy.
AB  - The electrodeposition nature of copper on a gold electrode in a 4.8 pH CuSO4
      solution was inquired using X-ray absorption spectroscopy, electrochemical quartz
      crystal microbalance, and thermal desorption spectroscopy techniques. Our results
      point out that the electrodeposition of copper prompts the formation of stable
      oxi-hydroxide species with a formal oxidation state Cu+ without the evidence of
      metallic copper formation (Cu0). Moreover, the subsequent anodic polarization of
      Cu2Oaq yields the formation of CuO, in the formal oxidation state Cu2+, which is
      dissolved at higher anodic potential. It was found that the dissolution process
      needs less charge than that required for the electrodeposition indicating a
      nonreversible process most likely due to concomitant water splitting and
      formation of protons during the electrodeposition.

PMID- 29039939
TI  - Structural Engineering in Plasmon Nanolasers.
AB  - This review focuses on structural engineering of lasers from the macroscale to
      the nanoscale, with an emphasis on plasmon nanolasers. Conventional lasers based
      on Fabry-Perot cavities are limited in device size. In contrast, plasmon
      nanolasers can overcome the diffraction limit of light and incorporate unique
      structural designs to engineer cavity geometries and optical band structure.
      Since the spaser concept was introduced in 2003, tremendous progress in
      nanolasing has been made on architectures that exploit metal films and
      nanoparticles. Theoretical approaches in both frequency and time domains have
      inspired the development of plasmon nanolasers based on mode analysis and time
      dependent lasing buildup. Plasmon nanolasers designed by band-structure
      engineering open prospects for manipulation of lasing characteristics such as
      directional emission, real-time tunable wavelengths, and controlled multimode
      lasing.

PMID- 29039940
TI  - NosN, a Radical S-Adenosylmethionine Methylase, Catalyzes Both C1 Transfer and
      Formation of the Ester Linkage of the Side-Ring System during the Biosynthesis of
      Nosiheptide.
AB  - Nosiheptide, a member of the e series of macrocyclic thiopeptide natural
      products, contains a side-ring system composed of a 3,4-dimethylindolic acid
      (DMIA) moiety connected to Glu6 and Cys8 of the thiopeptide backbone via ester
      and thioester linkages, respectively. Herein, we show that NosN, a predicted
      class C radical S-adenosylmethionine (SAM) methylase, catalyzes both the transfer
      of a C1 unit from SAM to 3-methylindolic acid linked to Cys8 of a synthetic
      substrate surrogate as well as the formation of the ester linkage between Glu6
      and the nascent C4 methylene moiety of DMIA. In contrast to previous studies that
      indicated that 5'-methylthioadenosine is the immediate methyl donor in the
      reaction, in our studies, SAM itself plays this role, giving rise to S
      adenosylhomocysteine as a coproduct of the reaction.

PMID- 29039941
TI  - C-H...O Hydrogen Bonding. The Prototypical Methane-Formaldehyde System: A
      Critical Assessment.
AB  - Distinguishing the functionality of C-H...O hydrogen bonds (HBs) remains
      challenging, because their properties are difficult to quantify reliably. Herein,
      we present a study of the model methane-formaldehyde complex (MFC). Six
      stationary points on the MFC potential energy surface (PES) were obtained at the
      CCSD(T)/ANO2 level. The CCSDT(Q)/CBS interaction energies of the conformers range
      from only -1.12 kcal mol-1 to -0.33 kcal mol-1, denoting a very flat PES.
      Notably, only the lowest energy stationary point (MFC1) corresponds to a genuine
      minimum, whereas all other stationary points-including the previously studied
      ideal case of ae(C-H...O) = 180 degrees -exhibit some degree of freedom that
      leads to MFC1. Despite the flat PES, we clearly see that the HB properties of
      MFC1 align with those of the prototypical water dimer O-H...O HB. Each HB
      property generally becomes less prominent in the higher-energy conformers. Only
      the MFC1 conformer prominently exhibits (1) elongated C-H donor bonds, (2)
      attractive C-H...O?C interactions, (3) n(O) -> sigma*(C-H) hyperconjugation, (4)
      critical points in the electron density from Bader's method and from the
      noncovalent interactions method, (5) positively charged donor hydrogen, and (6)
      downfield NMR chemical shifts and nonzero 2J(CM-HM...OF) coupling constants.
      Based on this research, some issues merit further study. The flat PES hinders
      reliable determinations of the HB-induced shifts of the C-H stretches; a
      similarly difficult challenge is observed for the experiment. The role of charge
      transfer in HBs remains an intriguing open question, although our BLW and NBO
      computations suggest that it is relevant to the C-H...O HB geometries. These
      issues notwithstanding, the prominence of the HB properties in MFC1 serves as
      clear evidence that the MFC is predominantly bound by a C-H...O HB.

PMID- 29039942
TI  - Correlating Resolving Power, Resolution, and Collision Cross Section: Unifying
      Cross-Platform Assessment of Separation Efficiency in Ion Mobility Spectrometry.
AB  - Here we examine the relationship among resolving power (Rp), resolution (Rpp),
      and collision cross section (CCS) for compounds analyzed in previous ion mobility
      (IM) experiments representing a wide variety of instrument platforms and IM
      techniques. Our previous work indicated these three variables effectively
      describe and predict separation efficiency for drift tube ion mobility
      spectrometry experiments. In this work, we seek to determine if our previous
      findings are a general reflection of IM behavior that can be applied to various
      instrument platforms and mobility techniques. Results suggest IM distributions
      are well characterized by a Gaussian model and separation efficiency can be
      predicted on the basis of the empirical difference in the gas-phase CCS and a CCS
      based resolving power definition (CCS/DeltaCCS). Notably traveling wave (TWIMS)
      was found to operate at resolutions substantially higher than a single-peak
      resolving power suggested. When a CCS-based Rp definition was utilized, TWIMS was
      found to operate at a resolving power between 40 and 50, confirming the previous
      observations by Giles and co-workers. After the separation axis (and
      corresponding resolving power) is converted to cross section space, it is
      possible to effectively predict separation behavior for all mobility techniques
      evaluated (i.e., uniform field, trapped ion mobility, traveling wave, cyclic, and
      overtone instruments) using the equations described in this work. Finally, we are
      able to establish for the first time that the current state-of-the-art ion
      mobility separations benchmark at a CCS-based resolving power of >300 that is
      sufficient to differentiate analyte ions with CCS differences as small as 0.5%.

PMID- 29039943
TI  - Synthesis and Structural, Electrical, and Magnetic Properties of New Iron
      Aluminum Alluaudite Phases beta-Na2Ni2M(PO4)3 (M = Fe and Al).
AB  - Herein we report the studies of different physical properties (structural,
      magnetic, thermal, morphologic, electrical, and electrochemical) of two new
      allotropic beta-Na2Ni2M(PO4)3 (NNMP) phosphates, with M = Fe and Al. Pure
      orthorhombic single-phase powders were prepared under air, using an
      autocombustion synthesis method. They crystallize in the orthorhombic Imma space
      group with similar unit cell parameters [a = 10.1592(2), b = 13.0321(3), c =
      6.4864(2) A] and [a = 10.3993(1), b = 13.1966(1), c = 6.4955(1) A] for beta
      Na2Ni2M(PO4)3 (NNAP) and beta-Na2Ni2Fe(PO4)3 (NNFP), respectively. Crystal
      structures of both compounds were determined using X-ray powder diffraction and
      Rietveld method refinements, which indicate the occurrence of Ni2+ in the 8g
      site, and of M3+ in the 4a site of the structure. The structure consists of a
      three-dimensional anionic framework obtained by the association on MO6, NiO6, and
      PO4 polyhedra, sharing edges and corners. The resulting three-dimensional
      structure creates monodimensional channels along the [100] and [010] directions
      formed by face-shared oxygen polyhedra and occupied by Na+ cations. This
      nondisordered cationic distribution is confirmed by a significant change of
      magnetic properties. Thus, both NNAP and NNFP samples show paramagnetic to
      ferromagnetic transition at 14 and 19 K, respectively. For the two compounds,
      thermal stability, electrical conductivity, and electrochemical properties have
      been also investigated. The intercalation/desintercalation properties of NNMP
      compounds as positive electrode were tested in sodium-ion batteries. The first
      cycling curves exhibit a significant polarization for both prepared samples.

PMID- 29039944
TI  - 3D-Printed Microflow Injection Analysis Platform for Online Magnetic Nanoparticle
      Sorptive Extraction of Antimicrobials in Biological Specimens as a Front End to
      Liquid Chromatographic Assays.
AB  - In this work, the concept of 3D-printed microflow injection (3D-MUFI) embodying a
      dedicated multifunctional 3D-printed stator onto a rotary microvalve along with a
      mesofluidic sample preparation platform is proposed for the first time. A
      transparent 3D-printed stereolithographic mesofluidic chip device accommodating
      polyaniline (PANI) decorated magnetic nanoparticles (32.5 +/- 3.8 mg) is
      harnessed to in-line sorptive microextraction as a front end to liquid
      chromatography with peak focusing. As a proof-of-concept application, the 3D-MUFI
      assembly was resorted to matrix cleanup and automatic programmable-flow
      determination of organic emerging contaminants (4-hydroxybenzoate analogues and
      triclosan as antimicrobial model analytes) in human saliva and urine samples. By
      using a sample volume of 1.0 mL with a loading flow rate of 200 MUL min-1, an
      eluent volume of 120 MUL at 80 MUL min-1, and online HPLC injection of 300 MUL of
      the mixture of eluate and Milli-Q water (in a 1:2 ratio) to prevent band
      broadening effects of the most polar analytes, the limits of detection (3sigma
      criterion) ranged from 1.1 to 4.5 ng mL-1 for methylparaben (MP), ethylparaben
      (EP), propylparaben (PrP), phenylparaben (PhP), butylparaben (BP), and triclosan
      (TCS). Enhancement factors of 16-25 were obtained for the target analytes. Spike
      recoveries ranged from 84 to 117% for both saliva and urine samples. The online
      3D-MUFI hyphenated method is synchronized with the chromatographic separation and
      features a chip lifetime of more than 20 injections with minimal losses of
      moderately nonpolar compounds on the walls of the mesofluidic device.

PMID- 29039945
TI  - Structural Consequences of 1,4-Cyclohexanedicarboxylate Cis/Trans Isomerism in
      Uranyl Ion Complexes: From Molecular Species to 2D and 3D Entangled Nets.
AB  - trans-1,4-Cyclohexanedicarboxylic acid (t-1,4-chdcH2) or the commercially
      available mixture of the cis and trans isomers (c,t-1,4-chdcH2) has been used in
      the synthesis of a series of 14 uranyl ion complexes, all obtained under
      solvohydrothermal conditions, some in the presence of additional metal cations
      and/or 2,2'-bipyridine (bipy). With its two isomeric forms having very different
      shapes and its great sensitivity to the experimental conditions, 1,4-chdc2-
      appears to be suitable for the synthesis of uranyl ion complexes displaying a
      wide range of architectures. Under the conditions used, the pure trans isomer
      gives only the complexes [UO2(t-1,4-chdc)(H2O)2] (1) and [UO2(t-1,4-chdc)] (2),
      which crystallize as one- and two-dimensional (1D and 2D) species, respectively.
      Complexes containing either the cis isomer alone or mixtures of the two isomers
      in varying proportion were obtained from the isomer mixture. The neutral
      complexes [UO2(c-1,4-chdc)(DMF)] (3) and [UO2(c-1,4-chdc)(bipy)] (4) are 2D and
      1D assemblies, respectively, while all the other complexes are anionic and
      include various counterions. [C(NH2)3]3[H2NMe2][(UO2)4(c-1,4-chdc)6].H2O (5)
      crystallizes as a three-dimensional (3D) framework with {103} topology. While
      [H2NMe2]2[(UO2)2(c-1,4-chdc)2(t-1,4-chdc)].DMF.2H2O (6) is a 1D ladderlike
      polymer, [H2NMe2]2[(UO2)2(c-1,4-chdc)(t-1,4-chdc)2].2H2O (7), which differs in
      the cis/trans ratio, is a 3-fold 2D interpenetrated network with {63} honeycomb
      topology. The related [H2NMe2]2[(UO2)2(c,t-1,4-chdc)3].2.5H2O (8), with one
      disordered ligand of uncertain geometry, is a 3-fold 3D interpenetrated system.
      The two isomorphous complexes [Co(bipy)3][(UO2)2(c-1,4-chdc)3].1.5H2O (9) and
      [Cd(bipy)3][(UO2)2(c-1,4-chdc)3].1.5H2O (10) form 3D frameworks with the {103}
      srs topological type. In contrast, [Ni(bipy)3]2[(UO2)4(c-1,4-chdc)2(t-1,4
      chdc)(NO3)6].2H2O (11) is a molecular, tetranuclear complex due to the presence
      of terminal nitrate ligands. A 2-fold 3D interpenetration of frameworks with
      {103} ths topology is observed in [Cu(bipy)2]2[(UO2)2(c-1,4-chdc)2(t-1,4
      chdc)].2H2O (12), while [Zn(bipy)3][(UO2)2(c-1,4-chdc)3].4H2O (13) crystallizes
      as a 2D net with the common {4.82} fes topological type. The additional PbII
      cation is an essential part of the 3D framework formed in [UO2Pb2(c-1,4-chdc)(t
      1,4-chdc)2(bipy)2] (14), in which uranyl and its ligands alone form 1D subunits.
      Together with previous results, the solid-state uranyl emission properties of
      seven of the present complexes evidence a general trend, with the maxima for the
      complexes with O6 equatorial environments being blue-shifted with respect to
      those for complexes with O5 environments.

PMID- 29039946
TI  - Phenylpropenoids from Bupleurum fruticosum as Anti-Human Rhinovirus Species A
      Selective Capsid Binders.
AB  - The dichloromethane extract of the leaves of Bupleurum fruticosum was found to
      inhibit the replication of human rhinovirus (HRV) serotypes 14 and 39. Bioassay
      guided fractionation led to the isolation of seven phenylpropenol derivatives (3
      9), two polyacetylenes (1 and 2), and one monoterpene (10). Compounds 1 and 10
      were identified as previously undescribed secondary metabolites after extensive
      1D and 2D NMR experiments as well as high-resolution mass spectrometry. Compounds
      2, 4, and 5 showed a selective inhibition of viral replication against HRV39
      serotype, with 2 and 4 being the most active, with EC50 values of 1.8 +/- 0.02
      and 2.4 +/- 0.04 MUM. Mechanism of action studies indicated that 4 behaves not
      only as a capsid binder, interfering with the early phases of virus replication,
      but also as a late-phase replication inhibitor. Docking experiments were
      performed to confirm the ability of the antiviral phenylpropenoids to selectively
      fit into the hydrophobic pocket of VP1-HRV39.

PMID- 29039947
TI  - Revision of the Absolute Configuration of Preussilides A-F Established by the
      Exciton Chirality Method.
AB  - In a recent contribution to this Journal (J. Nat. Prod. 2017, 80, 1531-1540),
      Noumeur et al. reported the isolation and structure elucidation of six novel
      polyketides named preussilides A-F, endowed with remarkable antiproliferative
      activity. The absolute configuration of the new compounds was established mainly
      by analyzing exciton-coupled electronic circular dichroism (ECD) spectra.
      However, the application of the exciton chirality method (ECM) was incorrect,
      because the chirality defined by transition moments was assigned in a wrong way.
      A correct application of the ECM, substantiated by time-dependent density
      functional theory (TDDFT) calculations of ECD spectra, led us to revise the
      absolute configuration of Preussilides A-F. A brief discussion on the criteria
      required for a correct application of the ECM is also presented.

PMID- 29039948
TI  - Photoassisted Homocoupling of Methyl Iodide Mediated by Atomic Gold in Low
      Temperature Neon Matrix.
AB  - Infrared spectroscopy and density functional theory calculations showed that the
      gold complexes [CH3-Au-I] and [(CH3)2-Au-I2], in which one and two CH3I
      molecule(s), respectively, are oxidatively adsorbed on the Au atoms, are formed
      in a solid neon matrix via reactions between laser-ablated gold atoms and CH3I.
      Global reaction route mapping calculations revealed that the heights of the
      activation barriers for the sequential oxidative additions to produce [CH3-Au-I]
      and [(CH3)2-Au-I2] are 0.53 and 1.00 eV, respectively, suggesting that the
      reactions proceed via electronically excited states. The reductive elimination of
      ethane (C2H6) from [(CH3)2-Au-I2] leaving AuI2 was hindered by an activation
      barrier as high as 1.22 eV but was induced by visible-light irradiation on
      [(CH3)2-Au-I2]. These results demonstrate that photoassisted homocoupling of CH3I
      is mediated by Au atoms via [(CH3)2-Au-I2] as an intermediate.

PMID- 29039949
TI  - Highly Efficient Red-Emitting Carbon Dots with Gram-Scale Yield for Bioimaging.
AB  - Carbon dots (CDs) are a new class of photoluminescent (PL), biocompatible,
      environment-friendly, and low-cost carbon nanomaterials. Synthesis of highly
      efficient red-emitting carbon dots (R-CDs) on a gram scale is a great challenge
      at present, which heavily restricts the wide applications of CDs in the
      bioimaging field. Herein, R-CDs with a high quantum yield (QY) of 53% are
      produced on a gram scale by heating a formamide solution of citric acid and
      ethylenediamine. The as-prepared R-CDs have an average size of 4.1 nm and a
      nitrogen content of about 30%, with an excitation-independent emission at 627 nm.
      After detailed characterizations, such strong red fluorescence is ascribed to the
      contribution from the nitrogen- and oxygen-related surface states and the
      nitrogen-derived structures in the R-CD cores. Our R-CDs show good photostability
      and low cytotoxicity, and thus they are excellent red fluorescence probes for
      bioimaging both in vitro and in vivo.

PMID- 29039950
TI  - Calorimetric and Spectroscopic Studies of the Effects of the Cell Penetrating
      Peptide Pep-1 and the Antimicrobial Peptide Combi-2 on Vesicles Mimicking
      Escherichia coli Membrane.
AB  - The objective of this study is to measure and compare the effects of the cell
      penetrating peptide (CPP) Pep-1 and the antimicrobial peptide (AMP) combi-2 on
      vesicles of membranes mimicking Escherichia coli (E. coli). To characterize the
      effects of Pep-1 and combi-2 on E. coli membrane vesicles, a combination of five
      biophysical techniques was employed: fluorescence, infrared, scanning electron
      microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning
      calorimetry (DSC) techniques. Upon addition of E. coli membranes, tryptophan
      fluorescence intensity of Pep-1 showed a sudden blue-shift and decreased in a
      nonconcentration-dependent manner while the intensity of combi-2 decreased in a
      concentration-dependent manner, most significantly for a very low peptide-to
      lipid ratio of 1:40. Complexes of Pep-1 and combi-2 with E. coli membrane
      mimicking vesicles having shown a significant blue-shift in fluorescence
      intensity were then prepared and studied in freeze-dried states. IR results
      indicate that Pep-1 and combi-2 adopt a major 310-helix structure in the presence
      of E. coli membrane mimicking vesicles at low peptide concentration. Pep-1 and
      combi-2 have a similar effect on E. coli membrane mimicking vesicles at low
      concentration even though combi-2 is in the interfacial region of the bilayer
      while Pep-1 is located between the interfacial region and the hydrophobic region.
      Combi-2 at low concentration acts as a CPP. TGA and DSC results reveal that combi
      2 has a stabilizing effect on E. coli at any concentration while Pep-1 stabilizes
      the E. coli membrane only at high concentration. Both peptides show a
      preferential interaction with one of the anionic lipids leading to clustering in
      E. coli membrane. SEM images reveal that Pep-1 and combi-2 form superstructures
      including fibrils in the presence of E. coli membrane mimicking vesicles.
      Calorimetric and spectroscopic techniques may be used in a complementary way with
      imaging techniques to gain more insights into peptide-lipid interactions.

PMID- 29039951
TI  - 1,2-Fluorine Radical Rearrangements: Isomerization Events in Perfluorinated
      Radicals.
AB  - Devising effective degradation technologies for perfluoroalkyl substances (PFASs)
      is an active area of research, where the molecular mechanisms involving both
      oxidative and reductive pathways are still elusive. One commonly neglected
      pathway in PFAS degradation is fluorine atom migration in perfluoroalkyl
      radicals, which was largely assumed to be implausible because of the high C-F
      bond strength. Using density functional theory calculations, it was demonstrated
      that 1,2-F atom migrations are thermodynamically favored when the fluorine atom
      migrated from a less branched carbon center to a more branched carbon center.
      Activation barriers for these rearrangements were within 19-29 kcal/mol, which
      are possible to easily overcome at elevated temperatures or in photochemically
      activated species in the gas or aqueous phase. It was also found that the
      activation barriers for the 1,2-F atom migration are lowered as much as by 10
      kcal/mol when common oxidative degradation products such as HF assisted the
      rearrangements or if the resulting radical center was stabilized by vicinal pi
      bonds. Natural bond orbital analyses showed that fluorine moves as a radical in a
      noncharge-separated state. These findings add an important reaction to the
      existing knowledge of mechanisms for PFAS degradation and highlights the fact
      that 1,2-F atom shifts may be a small channel for isomerization of these
      compounds, but upon availability of mineralization products, this isomerization
      process could become more prominent.

PMID- 29039952
TI  - Chloromonilinic Acids C and D, Phytotoxic Tetrasubstituted 3-Chromanonacrylic
      Acids Isolated from Cochliobolus australiensis with Potential Herbicidal Activity
      against Buffelgrass (Cenchrus ciliaris).
AB  - The fungal pathogen Cochliobolus australiensis isolated from infected leaves of
      the invasive weed buffelgrass (Pennisetum ciliare) was grown in vitro to evaluate
      its ability to produce phytotoxic metabolites that could potentially be used as
      natural herbicides against this weed. Two new tetrasubstituted 3-chromanonacrylic
      acids, named chloromonilinic acids C (1) and D (2), were isolated from the liquid
      cultures of C. australiensis, together with the known chloromonilinic acid B.
      Chloromonilinic acids C and D were characterized by spectroscopic and chemical
      methods as (E)-3-chloro-3-[(5-hydroxy-3-(1-hydroxy-2-methoxy-2-oxoethyl)-7-methyl
      4-oxo-4H-chromen-2-yl)]acrylic acid and (Z)-3-chloro-3-[(5-hydroxy-3-(2-methoxy-2
      oxoethyl)-7-methyl-4-oxo-4H-chromen-2-yl)]acrylic acid, respectively. The
      stereochemistry of chloromonilinic acids C and D was determined using a
      combination of spectroscopic and computational methods, including electronic
      circular dichroism. The fungus produced these compounds in two different liquid
      media together with cochliotoxin, radicinin, radicinol, and their 3-epimers. The
      radicinin-related compounds were also produced when the fungus was grown in wheat
      seed solid culture, but chloromonilinic acids were not found in the solid culture
      organic extract. All three chloromonilinic acids were toxic to buffelgrass in a
      seedling elongation bioassay, with significantly delayed germination and
      dramatically reduced radicle growth, especially at a concentration of 5 * 10-3 M.

PMID- 29039953
TI  - Phosphoryl Transfer Reaction in RNA: Is the Substrate-Assisted Catalysis a
      Possible Mechanism in Certain Solvents?
AB  - A proton shuttle mechanism for the phosphoryl transfer reaction in RNA, in which
      a proton is transferred from the nucleophile to the leaving group through a
      nonbridged oxygen atom of the phosphate, was explored using the MO6-2X density
      functional method and the solvent continuum model. This reaction is the initial
      step of the RNA hydrolysis. We used different solvents characterized by their
      dielectric constant, and, for each of them, we studied the nuclear and electronic
      relaxation, produced by the solvent reaction field, for the stationary points.
      Given that RNA has a poor leaving group, the bond breaking corresponds to the
      rate-determining step. If the O atom is substituted by a S atom, the leaving
      group is now good, and the rate-determining step is now the nucleophilic attack
      concerted with the proton transfer. The most relevant result we found is that
      none of the solvents we studied has a free energy of activation that is smaller
      than the one in water. This suggests that the enzyme catalysis following this
      mechanism must be due to the permanent electric field that is created by a
      preorganized charge distribution but not to the solvent reaction field.

PMID- 29039954
TI  - A Versatile Method for the Distance-Dependent Structural Characterization of
      Interacting Soft Interfaces by Neutron Reflectometry.
AB  - Interactions between soft interfaces govern the behavior of emulsions and foams
      and crucially influence the functions of biological entities like membranes. To
      understand the character of these interactions, detailed insight into the
      interfaces' structural response in terms of molecular arrangements and
      conformations is often essential. This requires the realization of controlled
      interaction conditions and surface-sensitive techniques capable of resolving the
      structure of buried interfaces. Here, we present a new approach to determine the
      distance-dependent structure of interacting soft interfaces by neutron
      reflectometry. A solid/water interface and a water/oil interface are
      functionalized independently and initially macroscopically separated. They are
      then brought into contact and structurally characterized under interacting
      conditions. The nanometric distance between the two interfaces can be varied via
      the exertion of osmotic pressures. Our first experiments on lipid-anchored
      polymer brushes interacting across water with solid-grafted polyelectrolyte
      brushes and with bare silicon surfaces reveal qualitatively different interaction
      scenarios depending on the chemical composition of the two involved interfaces.

PMID- 29039955
TI  - Critical Role of Ultrathin Graphene Films with Tunable Thickness in Enabling
      Highly Stable Sodium Metal Anodes.
AB  - Sodium (Na) metal has shown great promise as an anode material for the next
      generation energy storage systems because of its high theoretical capacity, low
      cost, and high earth abundance. However, the extremely high reactivity of Na
      metal with organic electrolyte leads to the formation of unstable solid
      electrolyte interphase (SEI) and growth of Na dendrites upon repeated
      electrochemical stripping/plating, causing poor cycling performance, and serious
      safety issues. Herein, we present highly stable and dendrite-free Na metal anodes
      over a wide current range and long-term cycling via directly applying free
      standing graphene films with tunable thickness on Na metal surface. We
      systematically investigate the dependence of Na anode stability on the thickness
      of the graphene film at different current densities and capacities. Our findings
      reveal that only a few nanometer (~2-3 nm) differences in the graphene thickness
      can have decisive influence on the stability and rate capability of Na anodes. To
      achieve the optimal performance, the thickness of the graphene film covered on Na
      surface needs to be meticulously selected based on the applied current density.
      We demonstrate that with a multilayer graphene film (~5 nm in thickness) as a
      protective layer, stable Na cycling behavior was first achieved in carbonate
      electrolyte without any additives over 100 cycles at a current density as high as
      2 mA/cm2 with a high capacity of 3 mAh/cm2. We believe our work could be a viable
      route toward high-energy Na battery systems, and can provide valuable insights
      into the lithium batteries as well.

PMID- 29039956
TI  - Tetraarylphosphonium Salt-Catalyzed Synthesis of Oxazolidinones from Isocyanates
      and Epoxides.
AB  - Preparation of a range of oxazolidinones, including enantioenriched N-aryl
      substituted oxazolidinones, in which tetraarylphosphonium salts (TAPS) catalyze
      the [3 + 2] coupling reaction of isocyanates and epoxides effectively, is
      described. The key finding is a Bronsted acid/halide ion bifunctional catalyst
      that can accelerate epoxide ring opening with high regioselectivity. Mechanistic
      studies disclosed that the ylide generated from TAPS, along with the formation of
      halohydrins, plays a crucial role in the reaction with isocyanates.

PMID- 29039957
TI  - Directed Zincation or Magnesiation of the 2-Pyridone and 2,7-Naphthyridone
      Scaffold Using TMP Bases.
AB  - A regioselective zincation of the 2-pyridone and 2,7-naphthyridone scaffolds has
      been developed. Zincations of the methoxyethoxymethyl (MEM)-protected compounds
      using TMP2Zn.2MgCl2.2LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) followed by
      trapping with electrophiles provided functionalized 2-pyridones and 2,7
      naphthyridones. I/Mg exchange of iodinated 2-pyridone and 2,7-naphthyridone using
      i-PrMgCl.LiCl afforded magnesiated intermediates that reacted with electrophiles.
      A second magnesiation of the 2-pyridone scaffold was achieved by using
      TMPMgCl.LiCl. Additionally, we report CoCl2-catalyzed cross-couplings of the 1
      chloro-2,7-naphthyridines with arylzinc halides.

PMID- 29039958
TI  - Manginoids A-G: Seven Monoterpene-Shikimate-Conjugated Meroterpenoids with a
      Spiro Ring System from Guignardia mangiferae.
AB  - Manginoids A-G (1-7), seven monoterpene-shikimate-conjugated meroterpenoids with
      a spiro ring system, were isolated from Guignardia mangiferae. Compounds 1-4 are
      four isomers with epimeric and double-bond isomeric features possessing a 6
      oxaspiro[bicyclo[3.2.1]octane-3,5'-indene] ring, which represent the first
      examples of spiro meroterpenoids bearing a bridged spirocyclohexanedione moiety.
      Compounds 5 and 6 possess an unexpected 2,4-dioxatricyclo[3.3.1.03,7]nonane
      motif, which fuses with a 6-oxabicyclo[3.2.1]octane moiety. Compound 1 exhibits
      inhibitory activities against 11beta-hydroxysteroid dehydrogenase type 1 with an
      IC50 value of 0.84 MUM.

PMID- 29039959
TI  - Preparation of 1,2-Oxazetidines from Styrenes and Arylamines via a Peroxide
      Mediated [2 + 1 + 1] Cycloaddition Reaction.
AB  - The first regioselective synthesis of polysubstituted 1,2-oxazetidines, based on
      the [2 + 1 + 1] radical tandem cycloaddition of styrenes, arylamines, and tert
      butyl hydroperoxide (TBHP), is described. This simple and direct method allows
      the synthesis of 1,2-oxazetidines with a broad substrate scope from easily
      accessible materials. TBHP was employed in this conversion not only as the
      oxidant but also as the source of "O" for the carbonyl group in the products.

PMID- 29039960
TI  - Exciton-Coupled Electron Transfer Process Controlled by Non-Markovian
      Environments.
AB  - We theoretically investigate an exciton-coupled electron transfer (XCET) process
      that is conversion of an exciton into a charge transfer state. This conversion
      happens in an exciton transfer (XT) process, and the electron moves away in an
      electron transfer (ET) process in multiple environments (baths). This XCET
      process plays an essential role in the harvesting of solar energy in biological
      and photovoltaic materials. We develop a practical theoretical model to study the
      efficiency of the XCET process that occurs either in consecutive or concerted
      processes under the influence of non-Markovian baths. The role of quantum
      coherence in the XT-ET system and the baths is investigated using reduced
      hierarchal equations of motion (HEOM). This model includes independent baths for
      each XT and ET state, in addition to a XCET bath for the conversion process. We
      found that, while quantum system-bath coherence is important in the XT and ET
      processes, coherence between the XT and ET processes must be suppressed in order
      to realize that an efficient irreversible XCET process through the weak off
      diagonal interaction between the XT and ET bridge sites arises from an XCET bath.

PMID- 29039961
TI  - Symmetry and Structure of Cubic Semiconductor Surfaces.
AB  - A systematic stereographic approach to the description of surface symmetry and
      structure, applied previously to face-centered cubic, body-centered cubic, and
      hexagonal close-packed metals, is here extended to the surfaces of diamond
      structure and zinc-blende-structure semiconductors. A variety of symmetry
      structure combinations are categorized and the chiral properties of certain cases
      emphasized. A general condition for nonpolarity in the surfaces of zincblende
      materials is also noted.

PMID- 29039963
TI  - Simplified "No-D" NMR Methods for Routine Analysis and Organometallic Reagent
      Concentration Determination.
AB  - The use of tetrachloroethylene spiked with tetramethylsilane as a solvent for
      routine NMR analysis has been evaluated. Excellent quality spectra are reliably
      obtained, comparable to samples run in chloroform-d. Validation of this method is
      presented, together with the spectral data of commonly encountered trace
      impurities. In addition, NMR analysis for the concentration determination of
      organometallic reagents has been simplified using double-walled NMR tubes using a
      calibrated external reference solution within a hermetically sealed chamber.

PMID- 29039962
TI  - An Epoxide-Mediated Deprotection Method for Acidic Amide Auxiliary.
AB  - A practical method for the removal of a versatile acidic amide auxiliary has been
      developed. Facile alcoholysis of the amide in the presence of KOAc is enabled by
      an epoxide, which mechanistically resembles the removal of the Myers' auxiliary.
      The protocol has been applied to the removal of a variety of amide substrates and
      their C-H functionalization products with high efficiency and low cost,
      representing a step forward toward the development of a versatile directing group
      for C-H activation.

PMID- 29039964
TI  - Probing Linewidths and Biexciton Quantum Yields of Single Cesium Lead Halide
      Nanocrystals in Solution.
AB  - Cesium lead halide (CsPbX3, X = Cl, Br, I) perovskite nanocrystals (PNCs) have
      recently become a promising material for optoelectronic applications due to their
      high emission quantum yields and facile band gap tunability via both halide
      composition and size. The spectroscopy of single PNCs enhances our understanding
      of the effect of confinement on excitations in PNCs in the absence of obfuscating
      ensemble averaging and can also inform synthetic efforts. However, single PNC
      studies have been hampered by poor PNC photostability under confocal excitation,
      precluding interrogation of all but the most stable PNCs, and leading to a lack
      of understanding of PNCs in the regime of high confinement. Here, we report the
      first comprehensive spectroscopic investigation of single PNC properties using
      solution-phase photon-correlation methods, including both highly confined and
      blue-emitting PNCs, previously inaccessible to single NC techniques. With
      minimally perturbative solution-phase photon-correlation Fourier spectroscopy (s
      PCFS), we establish that the ensemble emission linewidth of PNCs of all sizes and
      compositions is predominantly determined by the intrinsic single PNC linewidth
      (homogeneous broadening). The single PNC linewidth, in turn, dramatically
      increases with increasing confinement, consistent with what has been found for II
      VI semiconductor nanocrystals. With solution-phase photon antibunching
      measurements, we survey the biexciton-to-exciton quantum yield ratio (BX/X QY) in
      the absence of user-selection bias or photodegradation. Remarkably, the BX/X QY
      ratio depends both on the PNC size and halide composition, with values between
      ~2% for highly confined bromide PNCs and ~50% for intermediately confined iodide
      PNCs. Our results suggest a wide range of underlying Auger rates, likely due to
      transitory charge carrier separation in PNCs with relaxed confinement.

PMID- 29039965
TI  - Scanning electron microscope comparative surface evaluation of glazed-lithium
      disilicate ceramics under different irradiation settings of Nd:YAG and Er:YAG
      lasers.
AB  - OBJECTIVE: To evaluate the surface of glazed lithium disilicate dental ceramics
      after irradiation under different irradiation settings of Nd:YAG and Er:YAG
      lasers using a scanning electron microscope (SEM). MATERIALS AND METHODS: Three
      glazed-press lithium disilicate ceramic discs were treated with HF, Er:YAG, and
      Nd:YAG, respectively. The laser-setting variables tested were laser mode,
      repetition rate (Hz), power (W), time of exposure (seconds), and laser energy
      (mJ). Sixteen different variable settings were tested for each laser type, and
      all the samples were analyzed by SEM at 500* and 1000* magnification. RESULTS:
      Surface analysis of the HF-treated sample showed a typical surface texture with a
      homogenously rough pattern and exposed ceramic crystals. Er:YAG showed no effect
      on the surface under any irradiation setting. The surface of Nd:YAG-irradiated
      samples showed cracking, melting, and resolidifying of the ceramic glaze. These
      changes became more pronounced as the power increased. At the highest power
      setting (2.25 W), craters on the surface with large areas of melted or
      resolidified glaze surrounded by globules were visible. However, there was little
      to no exposure of ceramic crystals or visible regular surface roughening.
      CONCLUSIONS: Neither Er:YAG nor Nd:YAG dental lasers exhibited adequate surface
      modification for bonding of orthodontic brackets on glazed lithium disilicate
      ceramics compared with the control treated with 9.5% HF.

PMID- 29039966
TI  - The Academy of Breastfeeding Medicine's Recent Past and Near Future.

PMID- 29039967
TI  - Central obesity and the Mediterranean diet: A systematic review of intervention
      trials.
AB  - Central obesity is associated with chronic low-grade inflammation, and is a risk
      factor for cardiometabolic syndrome. The Mediterranean diet pattern has a
      convincing evidence-base for improving cardiometabolic health. This review
      investigated the impact of Mediterranean diet interventions on central obesity,
      specifically. A systematic literature search was conducted in the MEDLINE,
      CINAHL, EMBASE and Cochrane library databases. Search terms included:
      'Mediterranean Diet', 'Mediterranean dietary pattern', 'central obesity' and
      'visceral fat'. The search was limited to English language and humans >=18 years.
      Eighteen articles met the eligibility criteria and reported at least one outcome
      measure of central obesity with Mediterranean diet intervention. Central obesity
      measures included waist circumference (16 studies), waist-hip ratio (5 studies)
      and visceral fat (2 studies). Thirteen (72%) of the studies, totaling 7186
      subjects (5168 subjects assigned to a Mediterranean Diet), reported a significant
      reduction in central obesity with a Mediterranean-type diet. However, seven out
      of these 13 interventions employed energy restriction, and only three showed a
      statistically significant favorable effect of the Mediterranean diet relative to
      a control group. This systematic review highlights the potential for a
      Mediterranean diet intervention to reduce central obesity and in turn reduce
      obesity-related chronic disease risk and associated public health burden.

PMID- 29039968
TI  - Characteristics, Biological Properties and Analytical Methods of Ursolic Acid: A
      Review.
AB  - Ursolic acid (UA) is a naturally occurring triterpenoid which is a promising
      candidate for the development of new therapeutic approaches and for the
      prevention and treatment of several diseases owing to its pharmacological
      importance. However, its low solubility in aqueous medium affects its therapeutic
      application. Several strategies have been used to overcome this obstacle. In this
      study, the incorporation of UA in to different drug delivery systems was found to
      be highly efficient. In addition, important investigations were performed about
      methods for qualitative and quantitative analyses of UA in various raw materials,
      including plants, biological fluids, and drug delivery systems, were
      investigated. Most recently high performance liquid chromatography coupled with
      various detectors, gas chromatography-mass spectrometry and capillary
      electrophoresis were used for this purpose. Thus, this review was performed to
      evaluate the biological effects of UA demonstrated thus far as well as the
      currently used, delivery systems and analytical methods.

PMID- 29039969
TI  - Clinical Outcomes and Failure Rates of Osteochondral Allograft Transplantation in
      the Knee: A Systematic Review.
AB  - BACKGROUND:: Cartilage lesions are a significant cause of morbidity and impaired
      knee function; however, cartilage repair procedures have failed to reproduce
      native cartilage to date. Thus, osteochondral allograft (OCA) transplantation
      represents a 1-step procedure to repair large chondral defects without the donor
      site morbidity of osteochondral autograft transplantation. PURPOSE:: To perform a
      systematic review of clinical outcomes and failure rates after OCA
      transplantation in the knee at a minimum mean 2 years' follow-up. STUDY DESIGN::
      Systematic review; Level of evidence, 4. METHODS:: A systematic review of the
      literature regarding the existing evidence for clinical outcomes and failure
      rates of OCA transplantation in the knee joint was performed using the Cochrane
      Database of Systematic Reviews, the Cochrane Central Register of Controlled
      Trials, PubMed, and MEDLINE from studies published between 1980 and 2017.
      Inclusion criteria were as follows: clinical outcomes and failure rates of OCAs
      for the treatment of chondral defects in the knee joint, English language, mean
      follow-up of 2 years and minimum follow-up of 18 months, minimum study size of 20
      patients, and human studies. The methodological quality of each study was
      assessed using a modified version of the Coleman methodology score. RESULTS:: The
      systematic search identified 19 studies with a total of 1036 patients. The mean 5
      year survival rate across the studies included in this review was 86.7% (range,
      64.1%-100.0%), while the mean 10-year survival rate was 78.7% (range, 39.0%
      93.0%). The mean survival rate was 72.8% at 15 years (range, 55.8%-84.0%) and
      67.5% at 20 years (range, 66.0%-69.0%). The weighted mean patient age was 31.5
      years (range, 10-82 years), and the weighted mean follow-up was 8.7 years (range,
      2-32 years). The following outcome measures showed significant improvement from
      preoperatively to postoperatively: d'Aubigne-Postel, International Knee
      Documentation Committee, Knee Society function, and Lysholm scores. The weighted
      mean reoperation rate was 30.2% (range, 0%-63%). The weighted mean failure rate
      was 18.2% (range, 0%-31%). Of note, revision cases, patellar lesions, and bipolar
      lesions demonstrated worse survival rates. CONCLUSION:: Improved patient-reported
      outcomes can be expected after OCA transplantation, with a survival rate of 78.7%
      at 10 years. Revision cases, patellar lesions, and bipolar lesions were
      associated with worse survival rates; therefore, utilization of the most
      appropriate index cartilage restoration procedure and proper patient selection
      are key to improving results.

PMID- 29039970
TI  - Food groups and risk of coronary heart disease, stroke and heart failure: A
      systematic review and dose-response meta-analysis of prospective studies.
AB  - BACKGROUND: Despite growing evidence for food-based dietary patterns' potential
      to reduce cardiovascular disease risk, knowledge about the amounts of food
      associated with the greatest change in risk of specific cardiovascular outcomes
      and about the quality of meta-evidence is limited. Therefore, the aim of this
      meta-analysis was to synthesize the knowledge about the relation between intake
      of 12 major food groups (whole grains, refined grains, vegetables, fruits, nuts,
      legumes, eggs, dairy, fish, red meat, processed meat, and sugar-sweetened
      beverages [SSB]) and the risk of coronary heart disease (CHD), stroke and heart
      failure (HF). METHODS: We conducted a systematic search in PubMed and Embase up
      to March 2017 for prospective studies. Summary risk ratios (RRs) and 95%
      confidence intervals (95% CI) were estimated using a random effects model for
      highest versus lowest intake categories, as well as for linear and non-linear
      relationships. RESULTS: Overall, 123 reports were included in the meta-analyses.
      An inverse association was present for whole grains (RRCHD: 0.95 (95% CI: 0.92
      0.98), RRHF: 0.96 (0.95-0.97)), vegetables and fruits (RRCHD: 0.97 (0.96-0.99),
      and 0.94 (0.90-0.97); RRstroke: 0.92 (0.86-0.98), and 0.90 (0.84-0.97)), nuts
      (RRCHD: 0.67 (0.43-1.05)), and fish consumption (RRCHD: 0.88 (0.79-0.99),
      RRstroke: 0.86 (0.75-0.99), and RRHF: 0.80 (0.67-0.95)), while a positive
      association was present for egg (RRHF: 1.16 (1.03-1.31)), red meat (RRCHD: 1.15
      (1.08-1.23), RRstroke: 1.12 (1.06-1.17), RRHF: 1.08 (1.02-1.14)), processed meat
      (RRCHD: 1.27 (1.09-1.49), RRstroke: 1.17 (1.02-1.34), RRHF: 1.12 (1.05-1.19)),
      and SSB consumption (RRCHD: 1.17 (1.11-1.23), RRstroke: 1.07 (1.02-1.12), RRHF:
      1.08 (1.05-1.12)) in the linear dose-response meta-analysis. There were clear
      indications for non-linear dose-response relationships between whole grains,
      fruits, nuts, dairy, and red meat and CHD. CONCLUSION: An optimal intake of whole
      grains, vegetables, fruits, nuts, legumes, dairy, fish, red and processed meat,
      eggs and SSB showed an important lower risk of CHD, stroke, and HF.

PMID- 29039971
TI  - Genome-Wide Analysis of the Transcription Start Sites and Promoter Motifs of
      Phytoplasmas.
AB  - Phytoplasmas are obligate intracellular parasitic bacteria that infect both
      plants and insects. We previously identified the sigma factor RpoD-dependent
      consensus promoter sequence of phytoplasma. However, the genome-wide landscape of
      RNA transcripts, including non-coding RNAs (ncRNAs) and RpoD-independent promoter
      elements, was still unknown. In this study, we performed an improved RNA
      sequencing analysis for genome-wide identification of the transcription start
      sites (TSSs) and the consensus promoter sequences. We constructed cDNA libraries
      using a random adenine/thymine hexamer primer, in addition to a conventional
      random hexamer primer, for efficient sequencing of 5'-termini of AT-rich
      phytoplasma RNAs. We identified 231 TSSs, which were classified into four
      categories: mRNA TSSs, internal sense TSSs, antisense TSSs (asTSSs), and orphan
      TSSs (oTSSs). The presence of asTSSs and oTSSs indicated the genome-wide
      transcription of ncRNAs, which might act as regulatory ncRNAs in phytoplasmas.
      This is the first description of genome-wide phytoplasma ncRNAs. Using a de novo
      motif discovery program, we identified two consensus motif sequences located
      upstream of the TSSs. While one was almost identical to the RpoD-dependent
      consensus promoter sequence, the other was an unidentified novel motif, which
      might be recognized by another transcription initiation factor. These findings
      are valuable for understanding the regulatory mechanism of phytoplasma gene
      expression.

PMID- 29039972
TI  - Targeted identification of adverse events in coronary artery disease patients
      based on patient-reported outcomes.
AB  - AIM: Can focusing the adverse events search to patients with poor patient
      reported outcome help in targeting adverse event detection? PATIENTS & METHODS:
      Coronary artery revascularization patients of the Kuopio University Hospital from
      June 2012 to August 2014 categorized into those with clinically significant
      improvement (15D score change >=0.015, n = 81) or deterioration (change >=-0.015,
      n = 64) in post-intervention health-related quality of life. RESULTS: Major
      complications (27 vs 9%, p = 0.004) or post-intervention infections (16 vs 5%, p
      = 0.031) were more common among those with deteriorated score. They also tended
      to have more cardiovascular (19 vs 9%, p = 0.071) and minor complications (16 vs
      7%, p = 0.118). CONCLUSION: Patient-reported outcomes may potentially help in
      targeting the adverse events search so that a larger number of adverse events can
      be identified for efficient learning from them.

PMID- 29039973
TI  - Amendment of vanadium-contaminated soil with soil conditioners: A study based on
      pot experiments with canola plants (Brassica campestris L.).
AB  - We performed pot experiments with canola plants (Brassica campestris L.) to
      evaluate the effect of eight soil conditioners on the amendment of vanadium (V)
      contaminated soil based on analysis of the growth of canola plants and the
      uptake, bioaccumulation, and translocation of heavy metals. Tested soil
      conditioners included polyacrylamide (PAM), sepiolite, humic acid (HAC), peat,
      sludge compost (SC), bentonite, lime, and fly ash. Results from the analysis of
      the growth of canola plants and the analysis of variance showed that the best
      soil conditioners for V-contaminated soil were 0.05-0.1 wt% PAM, 1 wt% peat, 1
      wt% HAC, and 1 wt% SC; moderately effective soil conditioners included sepiolite
      and lime. The best combination of soil conditioners was 0.1 wt% PAM, 1 wt% HAC,
      and 0.15 wt% lime, in addition of 1% ZVI, which increased the biomass and height
      of canola plants by 1.18-fold and 59.49%, respectively. We conclude that the best
      combination of soil conditioners determined from this study is promising for
      mitigating V contamination in soil.

PMID- 29039974
TI  - Role of kidney biomarkers [Kidney injury molecule-1, Calbindin, Interleukin-18
      and Monocyte chemoattractant protein-1] in HIV associated pre-eclampsia.
AB  - OBJECTIVE: Both HIV infection and pre-eclampsia (PE) are associated with
      considerable maternal mortality in South Africa. This study was designed to
      compare the urinary levels of kidney injury molecule-1 (KIM-1), calbindin,
      interleukin-18 (IL-18), and monocyte chemoattractant protein-1 (MCP-1) in HIV
      associated normotensive and preeclamptic pregnancies. METHODS: Following ethical
      approval and written consent, urine samples were collected from HIV negative (HIV
      -ve) normotensive pregnant (n = 19), HIV positive (HIV +ve) normotensive pregnant
      (n = 19), HIV -ve pre-eclamptic (n = 19) and HIV +ve pre-eclamptic (n = 19)
      women. The concentrations of KIM-1, calbindin, IL-18 and MCP-1 were assessed
      using the Bioplex technology. RESULTS: In contrast to IL-18 (p > 0.05) and MCP-1
      (p > 0.05), the concentrations of KIM-1 (p = 0.02) and calbindin (p = 0.02) were
      significantly higher in PE compared to normotensive pregnancies, irrespective of
      HIV status. Based on HIV status, all 4 analytes were similar between HIV+ve and
      HIV-ve groups. Urinary KIM-1 levels in the HIV -ve pre-eclamptics were
      significantly higher than those in the HIV -ve women with normal pregnancies (p =
      0.007). The maternal hypertension and/or HIV profile has no marked impact on the
      fetal weight. CONCLUSION: Our results demonstrate an increase in the urinary
      level of kidney injury molecule-1 and calbindin in PE, implicating their possible
      value as biomarkers of kidney injury. We observed no differences in the levels of
      KIM-1, IL-18, MCP-1 and calbindin based on HIV status. We propose that studies
      with larger sample sizes using these markers be conducted to establish their use
      as markers of diagnosing kidney injury in PE.

PMID- 29039975
TI  - Maternal and cord blood cyclophilin A in severe preeclampsia and normal pregnancy
      and its correlation with vitamin D and zinc.
AB  - OBJECTIVE: To investigate maternal and cord blood cyclophilin A level in severe
      preeclampsia compared with normal pregnancy and its correlation with vitamin D
      and zinc level. METHODS: We conducted a cross-sectional observational study of
      pregnant women who gave birth in Cipto Mangunkusumo Hospital between January and
      April 2014. RESULTS: Thirty-nine subjects were included. Subjects with severe
      preeclampsia have higher serum cyclophilin A levels compared with normotensive
      pregnancy (1299.60 vs. 1039.50; p 0.017). Maternal cyclophilin A, vitamin D, and
      zinc correlation were not statistically significant (p 0.189 & p 0.853).
      CONCLUSION: Cyclophilin A levels in severe preeclampsia is higher compared to
      normal pregnancy. There is no correlation between cyclophilin A, zinc, and
      vitamin D.

PMID- 29039976
TI  - Challenges and recommendations for the health-economic evaluation of primary
      prevention programmes for dementia.
AB  - OBJECTIVE: We aimed to review health-economic evaluations of (hypothetical)
      intervention programmes for the primary prevention of dementia, and highlight
      challenges and provide recommendations for future research to estimate its cost
      effectiveness. METHODS: We searched the databases PubMed, MODEM, CEA and NHS for
      publications on the cost-consequence, -effectiveness, -utility or -benefit
      analysis of (hypothetical) interventions to reduce the risk of developing
      dementia for persons without dementia, and described the study characteristics.
      RESULTS: Three publications described the evaluation of a hypothetical risk
      reduction due to physical activity or a multidomain intervention programme. Two
      studies reported a reduction of care costs. One study yielded two scenarios of
      increased care costs and one scenario of reduced care costs. Only one study
      reported the impact in QALY terms, and found a QALY gain. CONCLUSION: A few
      studies have evaluated a hypothetical multidomain prevention intervention, and
      reported that primary dementia prevention is potentially cost-saving or cost
      effective. Various challenges remain to evaluate the health-economic impact of
      prevention interventions, including extrapolation of short-term trial effects,
      care costs in the dementia-free and life years gained, and accurate
      representation of usual care. We recommend extensive sensitivity analyses to
      examine the impact of assumptions regarding these aspects on the outcomes of cost
      effectiveness studies.

PMID- 29039977
TI  - Chronic disruptions of circadian sleep regulation induce specific proinflammatory
      responses in the rat colon.
AB  - : Exposure to environmental conditions that disturb the daily rhythms has been
      shown to enhance the proinflammatory responses of immunostimulant-challenged
      immune system. However, it is not known whether circadian disturbances may
      stimulate unchallenged immune responses and thus contribute per se to the
      development of inflammation-related diseases. Our aim was to ascertain an effect
      of various conditions threatening the behavioral activity/rest cycle regulation,
      namely aging with or without melatonin, 6 h advance/delay phase shifts in the
      light/dark cycle repeated with a 2-day frequency and constant light, on
      expression of immune markers in the rat colon. The impact of these conditions on
      parameters of behavioral activity and mRNA levels of selected immune markers in
      the colonic mucosa of Wistar rats, namely TNFalpha (Tnf), IL1a (Il1a), IL17RA
      (Il17ra), STAT3 (Stat3) and Rgs16 (Rsg16), were detected. Our results demonstrate
      that aging with or without melatonin as well as repeated 6 h advance/delay phase
      shifts in the light/dark cycle, which increased inactivity as a correlate of
      sleep during the dark phase of the light/dark cycle (i.e. during the active phase
      for nocturnal animals), had a minor effect on immune state in the colonic mucosa;
      all these conditions caused downregulation of gene Rgs16 which is involved in
      attenuation of the inflammatory response in the colon but did not affect
      expression of the other immune markers. Interestingly, a long-term absence of
      melatonin facilitated the aging-induced effect on immune state in the colon. In
      contrast, exposure to constant light, which perturbed the interval of inactivity
      (sleep) and led to the complete abolishment of activity/inactivity cycles,
      activated robustly proinflammatory state in the colon selectively via Stat3
      dependent pathway. In spite all these experimental conditions (aging with or
      without melatonin, shifts in light/dark cycles, constant light) perturbed the
      activity/rest cycles, none of them induced sleep deprivation. These results
      provided the first evidence that disruptions in the behavioral
      activity/inactivity cycles may spontaneously (without immuno-stimulant) induce
      selective proinflammatory responses in the colonic mucosa. Such effects may take
      part in the mechanisms of modern lifestyle-induced inflammatory diseases of the
      gut. ABBREVIATIONS: B2M: beta2-microglobulin; DSS: dextran sodium sulfate; Gapdh:
      glyceraldehyde-3-phosphate dehydrogenase; Ifng: interferon g; Il1a: interleukin
      1a; Il1b: interleukin 1b; Il2: interleukin 2; Il6: interleukin 6; Il17ra:
      interleukin 17 receptor a; LD: light/dark cycle; LL: constant light; LPS:
      lipopolysaccharide; Mntr1a: melatonin receptor 1a; PINX: pinealectomy; Rgs16:
      regulator of G protein signaling 16; RT qPCR: quantitative reverse transcription
      polymerase chain reaction; Stat3: signal transducer and activator of
      transcription 3; Th17: type 17 T helper cells; Tnfalpha: tumor necrosis factor
      alpha; Tnfrsf1b: tumor necrosis factor receptor superfamily member 1b.

PMID- 29039978
TI  - Preimplantation genetic testing: current challenges and future prospects.
AB  - INTRODUCTION: Preimplantation genetic testing (PGT) is now a widely applied
      procedure in genetic practices and ART, with more than one third of ART Centers
      in US already utilizing PGT technology. Its indications have also been
      significantly extended to include common late-onset disorders and non-genetic
      conditions, such as testing for HLA match. Areas covered: This is a critical
      review of the developments in PGT, with emphasis on their outstanding limitations
      and directions for the future research and practice in the area of PGT. Expert
      commentary: The application of the new higher resolution PGT technologies has led
      to the identification of genetic variations, the biological and clinical
      importance of which is not sufficiently understood. It is obvious that the
      current selection process of embryos with the highest developmental potential
      requires a further improvement, as significant proportion of transferred euploid
      embryos still fail to result in an ongoing clinical pregnancy. More research will
      be needed to upgrade PGT for different conditions into a single universal test in
      the same biopsy material. To avoid a potential damage of embryo biopsy
      procedures, one of the important challenges will be the development of non
      invasive approaches to PGT.

PMID- 29039979
TI  - Single-Dose Pharmacokinetics of HLD200, a Delayed-Release and Extended-Release
      Methylphenidate Formulation, in Healthy Adults and in Adolescents and Children
      with Attention-Deficit/Hyperactivity Disorder.
AB  - OBJECTIVE: Current extended-release (ER) formulations of psychostimulants used
      for treatment of attention-deficit/hyperactivity disorder (ADHD) provide an
      extended duration of ADHD symptom control; however, the onset of efficacy can be
      protracted and variable, leaving the early morning untreated. The primary
      objective was to characterize the single-dose pharmacokinetics and tolerability
      of HLD200, an evening-dosed, delayed-release (DR) and ER formulation of
      methylphenidate (MPH), in healthy adults and in adolescents and children with
      ADHD. METHODS: The pharmacokinetics and tolerability of a single, oral evening
      dose of HLD200 (54 mg) were evaluated in two single-center open-label studies:
      the first in healthy adults (n = 12) and the second in adolescents (n = 18) and
      children (n = 11) with ADHD. Primary pharmacokinetic endpoints were the rate and
      extent of MPH absorption (Cmax and area under the curve [AUC]) and time to peak
      concentration (Tmax). These parameters were calculated using noncompartmental
      analysis. RESULTS: HLD200 produced a pharmacokinetic profile characterized by an
      8- to 10-hour delay in MPH release, followed by a period of extended controlled
      release, resulting in an ascending absorption profile that coincided with the
      early morning and afternoon. Mean values (coefficient of variation [CV]%) of
      weight-adjusted pharmacokinetic parameters were similar in adults and in
      adolescents and children with ADHD: Cmax ([ng/mL]/[mg/kg]) was 9.1 (35.2), 8.8
      (34.5), and 7.4 (30.1); AUC0-t ([ng . h/mL]/[mg/kg]) was 126.5 (35.5), 129.4
      (34.8), and 129.7 (27.3); and Tmax (hours) was 15.6 (11.1), 17.1 (14.5), and 17.7
      (14.1), respectively. Intersubject variability in the mean time to achieve
      ascending plasma MPH concentrations of 2, 3, 4, and 5 ng/mL was low (CV: 7.8%
      17.7%). CONCLUSIONS: Evening-dosed HLD200 produces the intended DR and ER
      pharmacokinetic profile that provides a consistent predictable delay in initial
      MPH release until the early morning, followed by extended release across the day.
      The body weight-adjusted pharmacokinetics of HLD200 were similar between adults
      and adolescents and children with ADHD.

PMID- 29039981
TI  - Calcitriol, the Active Metabolite of Vitamin D3, Inhibits Dry Eye Related Corneal
      Inflammation In Vivo and In Vitro.
AB  - PURPOSE: To examine the influence of topical administration of calcitriol on dry
      eye (DE) related corneal inflammation. METHODS: Benzalkonium chloride (BAC, 0.2%)
      was applied to induce DE. Then rats were treated topically with calcitriol (10
      6MUM). Tear break-up time (TBUT), fluorescein staining score, inflammatory index,
      and tear volume were measured. Corneal epithelium damage and corneal inflammation
      were examined by H&E staining or RT-qPCR. In vitro, human corneal epithelial
      cells (iHCEC) were cultured in hyperosmotic medium (450 mOsM) with various
      concentrations of calcitriol. Levels of pro-inflammatory mediators were measured
      by RT-qPCR or ELISA. NF-kappaB activation was examined by Western blotting and
      immunofluorescence staining. RESULTS: Calcitriol significantly ameliorated DE
      symptoms, attenuating corneal inflammation. In vitro studies showed that
      calcitriol significantly decreased the expression of pro-inflammatory mediators
      in iHCECs under hyperosmotic stress, probably through inhibiting NF-kappaB
      activation. CONCLUSION: The results suggest that calcitriol might be a potential
      therapeutic agent for DE.

PMID- 29039980
TI  - Advances in the Chromosome-Centric Human Proteome Project: looking to the future.
AB  - INTRODUCTION: The mission of the Chromosome-Centric Human Proteome Project (C
      HPP), is to map and annotate the entire predicted human protein set (~20,000
      proteins) encoded by each chromosome. The initial steps of the project are
      focused on 'missing proteins (MPs)', which lacked documented evidence for
      existence at protein level. In addition to remaining 2,579 MPs, we also target
      those annotated proteins having unknown functions, uPE1 proteins, alternative
      splice isoforms and post-translational modifications. We also consider how to
      investigate various protein functions involved in cis-regulatory phenomena,
      amplicons lncRNAs and smORFs. Areas covered: We will cover the scope, historic
      background, progress, challenges and future prospects of C-HPP. This review also
      addresses the question of how we can best improve the methodological approaches,
      select the optimal biological samples, and recommend stringent protocols for the
      identification and characterization of MPs. A new strategy for functional
      analysis of some of those annotated proteins having unknown function will also be
      discussed. Expert commentary: If the project moves well by reshaping the original
      goals, the current working modules and team work in the proposed extended
      planning period, it is anticipated that a progressively more detailed draft of an
      accurate chromosome-based proteome map will become available with functional
      information.

PMID- 29039982
TI  - Botryomycosis: A surprising revelation in the lacrimal sac.
AB  - A middle aged woman presented to us with a localised well defined swelling of 3
      months duration. It was located just below the lower eyelid punctum and was
      constantly discharging whitish granules. We suspected it to be arising from the
      lacrimal apparatus and posted the patient for Dacryocystectomy. On the operating
      table we found a swelling in the region of the lacrimal sac which was later
      excised. Histopathology revealed Botryomycosis and Chronic Dacryocystitis.
      Botryomycosis is a rare condition and requires a high index of suspicion to
      diagnose it. It is confirmed by histopathology and culture. Surgical debridement
      is the treatment of choice in such cases with an assessment of the immune status.
      Long term antibiotic treatment is required in all conditions as recurrence is
      common.

PMID- 29039983
TI  - Potential Information Loss Due to Categorization of Minimum Inhibitory
      Concentration Frequency Distributions.
AB  - A bacterial isolate's susceptibility to antimicrobial is expressed as the lowest
      drug concentration inhibiting its visible growth, termed minimum inhibitory
      concentration (MIC). The susceptibilities of isolates from a host population at a
      particular time vary, with isolates with specific MICs present at different
      frequencies. Currently, for either clinical or monitoring purposes, an isolate is
      most often categorized as Susceptible, Intermediate, or Resistant to the
      antimicrobial by comparing its MIC to a breakpoint value. Such data
      categorizations are known in statistics to cause information loss compared to
      analyzing the underlying frequency distributions. The U.S. National Antimicrobial
      Resistance Monitoring System (NARMS) includes foodborne bacteria at the food
      animal processing and retail product points. The breakpoints used to interpret
      the MIC values for foodborne bacteria are those relevant to clinical treatments
      by the antimicrobials in humans in whom the isolates were to cause infection.
      However, conceptually different objectives arise when inference is sought
      concerning changes in susceptibility/resistance across isolates of a bacterial
      species in host populations among different sampling points or times. For the
      NARMS 1996-2013 data for animal processing and retail, we determined the fraction
      of comparisons of susceptibility/resistance to 44 antimicrobial drugs of twelve
      classes of a bacterial species in a given animal host or product population where
      there was a significant change in the MIC frequency distributions between
      consecutive years or the two sampling points, while the categorization-based
      analyses concluded no change. The categorization-based analyses missed
      significant changes in 54% of the year-to-year comparisons and in 71% of the
      slaughter-to-retail within-year comparisons. Hence, analyses using the breakpoint
      based categorizations of the MIC data may miss significant developments in the
      resistance distributions between the sampling points or times. Methods
      considering the MIC frequency distributions in their entirety may be superior for
      epidemiological analyses of resistance dynamics in populations.

PMID- 29039984
TI  - Financial Barriers and Lapses in Treatment and Care of HIV-Infected Adults in a
      Southern State in the United States.
AB  - Antiretroviral (ARV) adherence has largely been considered from the perspective
      of an individual's behavior with less attention given to potential structural
      causes for lapses in treatment, such as the cost of medications and care. HIV
      medication expense is typically covered by third party payers. However, private
      insurance premiums and deductibles may rise, or policies terminated such as with
      a change in employment. Likewise, a patient's eligibility for publicly funded
      coverage like state AIDS Drug Assistance Programs (ADAP) or Medicaid can also be
      lost. We conducted a one-time survey of a sample of 300 patients receiving HIV
      care at a single large academic center in the south of United States to examine
      lapses in HIV therapy due to financial reasons. We found that during the prior
      year, financial issues including medication cost or coverage led to a lapse in
      ARVs in 10% (n = 31) of participants. However, of the 42% (n = 125) participants
      who had been enrolled in ADAP at any time during the prior year, 21% (n = 26)
      reported an ARV lapse due to problems with ADAP or medication cost. Respondents
      cited ADAP's required semi-annual renewal process and other administrative issues
      as the cause of ARV lapses. The median duration of missed ARVs was 2 weeks (range
      of <1-23 weeks). Non-HIV medication and transportation to and from clinic costs
      were also identified as financial burdens to care by respondents. In conclusion,
      although conducted at a single medical center and one state, this study suggests
      that a significant minority of HIV-infected patients encounter financial barriers
      to ARV access, and this is paradoxically more common among those enrolled in the
      state ADAP. Streamlining, supporting, and simplifying ADAP renewal procedures
      will likely reduce lapses in ARV adherence and persistence.

PMID- 29039985
TI  - Radiofrequency surgery: 3500 years old and still young.
AB  - PURPOSE: To review the history of Radiofrequency surgery, delineate the actual
      situation and describe the applications in eyelid surgery. DESIGN: Review.
      METHODS: Review of literature, personal communication with several pioneers in
      the field, and own experience. CONCLUSION: Radiofrequency surgery has evolved
      from rude burning to a sophisticated surgical technique.

PMID- 29039986
TI  - Orbital exenteration: Institutional review of evolving trends in indications and
      rehabilitation techniques.
AB  - PURPOSE: To determine the changes in indications for orbital exenteration over 20
      years and to assess its impact on patient survival. Evolving techniques of
      rehabilitation of the orbit in our institution were also evaluated. METHODS: This
      was a retrospective review of hospital records of patients who underwent orbital
      exenteration from 1995 to 2015 in a tertiary care center. Data extracted included
      primary location of the tumor, preoperative treatments, interval between initial
      diagnosis and exenteration, status of surgical margins, presence of metastatic
      disease, and postoperative survival. The types of prosthesis utilized over the
      years were also reviewed. Cox regression analysis was performed for categorical
      variables. Kaplan-Meier analysis was used to estimate post-exenteration survival.
      RESULTS: Over a 20-year period, orbital exenteration was performed on 100 orbits
      of 100 patients. The mean age was 39.4 years (range: 2 months to 90 years). The
      most common indications among 98 malignant causes were retinoblastoma, squamous
      cell carcinoma, basal cell carcinoma, extraocular extension of uveal melanoma,
      and conjunctival melanoma. Postoperative survival was significantly related to
      age and tumor location but independent from gender, surgical margin,
      histopathological diagnosis, previous treatment modality, and preoperative
      interval. In the whole cohort, 1-year and 5-year survival rates were 97% and 84%,
      respectively. CONCLUSIONS: Exenteration appears to be life-saving in children
      with orbital extension of retinoblastoma. While patients exenterated for
      malignant eyelid tumors have the best chance of survival, those with orbital
      extension of uveal melanoma and adenoid cystic carcinoma of the lacrimal gland
      have the worst prognosis.

PMID- 29039987
TI  - A Propensity Score-Based Analysis of Laparoscopic Liver Resection for Liver
      Malignancies in Elderly Patients.
AB  - PURPOSE: Laparoscopic liver resection is safe, feasible and associated with less
      blood loss, shorter hospital stays and fewer postoperative complications in the
      working age patients with malignant liver tumors. However, it is still unclear if
      the elderly patients with malignant liver tumors would also benefit from that
      approach as the younger patients. So, the aim of the study was to compare the
      clinical outcomes of laparoscopic versus open liver resection for malignant liver
      tumors in elderly patients. MATERIALS AND METHODS: Between March 2009 and July
      2016, all elderly patients (>=70 years old) who underwent laparoscopic (n = 40)
      and open (n = 202) liver resection for malignant liver tumors were included. A
      one to one propensity score matching analysis was performed, based on 6
      covariates, to decrease the selection bias. RESULTS: There was no significant
      difference between the laparoscopic and open liver resection groups regarding the
      patient characteristics and tumor features. The operative time was comparable
      between both groups (Laparoscopic group 259 min vs Open group 308 min, p = .86),
      while patients who underwent laparoscopic liver resection had lower
      intraoperative blood loss (30 ml vs 517 ml, p < .0001), shorter hospital stays
      (10 days vs 23 days, p < .0001), and less overall morbidity (15% vs 38%, p =
      .04). The one-, three-, and five-year survival for patients with hepatocellular
      carcinoma was comparable between both groups (Laparoscopic group 96%, 74%, 47%,
      vs Open group 94%, 71%, 48%, p = .82), whereas The one-, three-, and five-year
      recurrence-free survival for patients with hepatocellular carcinoma was
      significantly higher in the laparoscopic group (88%, 60%, 60% vs 54%, 25%, 19%, p
      = .019). CONCLUSIONS: Laparoscopic approach for minor liver resection in elderly
      patients is safe and feasible with less blood loss, a shorter hospital stay, less
      postoperative complications and a better oncological outcome.

PMID- 29039988
TI  - The intraoperative use of polydioxanone foil to reduce the risk of sino-orbital
      fistula formation in orbital exenteration.
AB  - BACKGROUND: Orbital exenteration is a radical surgical procedure resulting in
      deformity. It involves removal of the globe, optic nerve, extra-ocular muscles,
      orbital fat, lacrimal gland, and peri-osteum. Sino-orbital fistula (SOF)
      formation is a common documented post-operative complication, usually connecting
      the orbit and the ethmoid sinus. SOFs can cause leaks of serous fluid, and act as
      an entry site for pathogens into the orbit leading to socket infection and
      breakdown. METHODS: This retrospective study analyzed exenterations performed
      over a 22-year period (1993-2015) at the National Ocular Oncology Service Centre
      for Scotland. PDS is a crystalline, biodegradable polyether-ester that is strong
      with good shape-memory and flexibility. Orbital exenterations with and without
      the use of PDS foil were compared in terms of SOF formation. RESULTS: A total of
      30 exenterations were performed during the study period. A total of 29 were
      analyzed. Choroidal malignant melanoma was the most common indication for
      performing orbital exenteration (n = 7, 24.14%). The most common post-operative
      complications seen were SOF (n = 8, 27.59%). A total of 8 out 21 (38.10%) cases
      not using PDS developed SOFs. By contrast, none of nine patients receiving PDS
      plates developed SOFs (p = 0.0332). CONCLUSIONS: This is the first study to
      compare SOF rate in patients undergoing exenteration with and without the use of
      PDS foil. PDS foil is a safe material, which has effectively reduced the
      incidence of SOF formation.

PMID- 29039989
TI  - Combination of clofarabine, cyclophosphamide, and etoposide for relapsed or
      refractory childhood and adolescent acute myeloid leukemia.
AB  - Relapsed/refractory acute myeloid leukemia (AML) has an extremely poor prognosis.
      We describe 17 children and adolescents with relapsed/refractory AML who received
      clofarabine, cyclophosphamide, and etoposide. Seven patients (41%) responded: 4
      with a complete response (CR); 1 with CR with incomplete platelet recovery; and 2
      with a partial response. Additionally, 4 developed hypocellular marrow without
      evidence of leukemia; 5 patients had resistant disease; and 1 suffered early
      toxic death. After further therapy including transplantation, 4 patients (24%)
      are alive without evidence of disease at a median of 60 months. This
      anthracycline-free regimen may be studied for relapsed or refractory AML, but due
      to the high risk of marrow aplasia reduced doses of clofarabine and
      cyclophosphamide should be used.

PMID- 29039990
TI  - Update on ST elevation Myocardial infarction.

PMID- 29039991
TI  - The effect of olive husk extract compared to the edta on Pb availability and some
      chemical and biological properties in a Pb-contaminated soil.
AB  - It was found that using chelating agents increases the efficiency of heavy metal
      extraction, however, they may have negative effects on soil ecosystem quality. A
      pot experiment was conducted in a completely randomized design with three
      replications in order to evaluate the effect of EDTA and Olive Husk Extract (OHE)
      on some chemical and biological properties of the Pb-contaminated soil. The
      experimental treatments included EDTA (2 g Na2EDTA salt per kg soil), OHE (2 g
      TDS of OHE per kg soil) and control (without the chelating agent). The results
      revealed that the EDTA and OHE treatments increased the Pb availability by 17.7%
      and 5.5% in comparison to the control treatment, respectively. Although EDTA was
      more effective in increasing the Pb availability but decreased the soil
      biological quality index (SBQI). The EDTA treatment significantly decreased the
      dehydrogenase (DH) activity and germination index (GI). The OHE application
      significantly increased the available-P, available-K, total N and organic carbon
      content by 339.92%, 40.79%, 20.9%, and 29.7% compared with control treatment,
      respectively. Furthermore, OHE considerably increased SBQI from 18.96 to 53.48.
      Compared to the control treatment higher values of soil respiration activity, DH
      activity, and carbon availability index (CAI) were observed in OHE treatment.

PMID- 29039992
TI  - Polymerase Chain Reaction and Goldmann-Witmer Coefficient to Examine the Role of
      Epstein-Barr Virus in Uveitis.
AB  - PURPOSE: To use polymerase chain reaction (PCR) and Goldmann-Witmer Coefficient
      (GWC) calculation to search for evidence that Epstein-Barr virus (EBV) causes
      uveitis. METHODS: A prospective cross-sectional study where participants with
      positive multiplex EBV PCR results were further investigated by: 1) real-time PCR
      for EBV viral loads (VL) and 2) EBV GWC. RESULTS: Eleven of 106 consecutive
      uveitis patients (10.4%) had positive multiplex PCR for EBV on aqueous humor
      sampling and 7/11 (63.6%) were HIV-positive. Only 4/10 (40%) cases had detectable
      intraocular EBV VLs which were always lower than the blood or plasma VL. EBV GWC
      was negative in all 10 cases tested. In 9/11 (81.8%) of these cases an
      alternative, more plausible cause of uveitis was identified. CONCLUSION: We found
      no evidence of active intraocular replication or antibody production to prove
      that EBV caused uveitis in these cases. In most cases an alternative treatable
      cause of uveitis was identified.

PMID- 29039993
TI  - Physical activity pre- and post-dementia: English Longitudinal Study of Ageing.
AB  - BACKGROUND: To inform public health interventions, further investigation is
      needed to identify: (1) frequency/intensity of everyday physical activity (PA)
      needed to reduce dementia risk; (2) whether post-diagnosis reduction in PA is
      associated with cognitive outcomes in people with dementia. METHODS: Data from
      11,391 men and women (aged >=50) were obtained from the English Longitudinal
      Study of Ageing cohort. Assessments were carried out at baseline (2002-2003) and
      at biannual follow-ups (2004-2013). RESULTS: Older adults who carried out
      moderate to vigorous activity at least once per week had a 34%-50% lower risk for
      cognitive decline and dementia over an 8-10 year follow-up period. From pre- to
      post-dementia diagnosis, those who decreased PA levels had a larger decrease in
      immediate recall scores, compared to those who maintained or increased PA levels
      (analyses were adjusted for changes in physical function). CONCLUSION: PA was
      associated with cognitive outcomes in a dose-dependent manner. Reduction in PA
      after diagnosis was associated with accelerated cognitive decline and maintaining
      PA may reduce symptom progression in dementia.

PMID- 29039994
TI  - Cell type-dependent localization of MLO proteins.
AB  - Mildew resistance locus O (MLO) proteins are transmembrane proteins that mediate
      cell-cell communication in plants. We recently demonstrated the importance of
      subcellular localization to MLO function during pollen tube reception. NORTIA
      (NTA), the MLO protein involved in this process, localizes to the Golgi of the
      synergid cell before interaction with the pollen tube. MLO proteins that can
      substitute for NTA's function in this pathway all partially localize with the
      same Golgi marker in the synergid cell. In this study, we report that MLO
      subcellular localization is cell type-dependent, with different distributions of
      some MLOs observed when ectopically expressed in the epidermal cells of tobacco
      and Arabidopsis compared to synergids. This dependency may be due to co-factors
      that influence MLO function within a given cell type, providing an intriguing new
      target for understanding MLO distribution and subsequent function in their
      respective processes.

PMID- 29039995
TI  - Preferred practice patterns in endoscopic dacryocystorhinostomy among
      oculoplastic surgeons in Asia-Pacific region.
AB  - PURPOSE: The aim of this study is to report the preferred practice patterns in
      endoscopic dacryocystorhinostomy (EnDCR) among oculoplastic surgeons practicing
      in the Asia-Pacific region. METHODS: A detailed survey with 40 questions was
      electronically disseminated among oculoplastic surgeons practicing in Asia
      Pacific region. The mailing list included targeted members of the Asia Pacific
      Society of Ophthalmic Plastic and Reconstructive Surgery and nonmembers from the
      contact directories of the two senior authors. Data collected include
      demographics, training, surgical techniques, postoperative care, and outcomes.
      RESULTS: The majority of surgeons performed a preoperative nasal endoscopy
      (76.2%, total respondents (n) = 122), and most preferred a general anesthesia for
      endoscopic DCRs (51.9%, n = 104). The majority of surgeons believed in preserving
      nasal mucosal and the lacrimal sac flaps and adjunctive endoscopic procedures
      were performed when required (58.4%, n = 101). Routine lacrimal sac wall biopsy
      for histopathology was not a preferred practice. The practice of routine silicone
      intubation was more common than the use of topical adjunctive. The majority of
      surgeons (52.6%, n = 97) took 31-60 minutes to complete a unilateral endoscopic
      DCR. Postoperative routine nasal douching and ostium cleaning were not widespread
      practices. The self-reported outcomes were good. CONCLUSION: A significantly high
      percentage of oculoplastic surgeons from Asia-Pacific perform endoscopic DCR.
      Although the range of practice patterns is wide, there is increasing uniformity
      in surgical techniques with regard to endoscopic DCR as compared to the previous
      surveys.

PMID- 29039996
TI  - Giant pleomorphic adenoma of the lacrimal gland: A surgical challenge.
AB  - Pleomorphic adenoma is the most common epithelial neoplasm of the lacrimal gland.
      The tumor typically presents with a superotemporal mass with inferonasal
      displacement of the globe. They generally measure less than 3 cm in size and can
      be removed comfortably via a lateral orbitotomy approach. Pleomorphic adenoma
      left unattended for a long period grows up to humongous proportions and poses a
      surgical challenge both for its complete removal and globe salvage. We report a
      rare case of pleomoprphic adenoma of the lacrimal gland in an adult male, who did
      not seek any medical advice for 20 years allowing the tumor to expand enormously
      in all dimensions, with complete obscuration of the globe. The tumor was excised
      completely and globe could be salvaged.

PMID- 29039997
TI  - Orbital T-cell lymphoma versus lupus panniculitits: a T-cell-mediated spectrum of
      orbital lymphoproliferative disease.
AB  - This is a case description of a single male patient found to have T-cell-mediated
      inflammation and lymphoproliferation of the orbit. Chronic T-cell-mediated
      inflammatory disease can pose a diagnostic challenge particularly in its
      differentiation from a neoplastic process. The histopathology in this case
      demonstrated features of both lupus erythematosus panniculitis and features of
      orbital T-cell lymphoma. While both are rare, lupus erythematosus panniculitis of
      the orbit is even more exceptional; this patient's indolent, chronic relapsing
      course distinguished itself from the typical aggression of orbital T-cell
      lymphoma. We believe this rare case may actually represent an example of a newly
      described disease spectrum that incorporates lupus erythematosus panniculitis as
      well as subcutaneous panniculitis-like T-cell lymphoma.

PMID- 29039998
TI  - FN1, FOS, and ITGA5 induce preeclampsia: Abnormal expression and methylation.
AB  - OBJECTIVE: As a frequent hypertensive disorder in pregnancy, preeclampsia causes
      15% of all preterm deliveries. This study aims to understand its mechanism via
      analyzing gene expression and methylation data. METHODS: Human gene expression
      microarray data (GSE73374) and corresponding DNA methylation microarray data
      (GSE73375) of preeclamptic placental tissues (n = 19) and normotensive placental
      tissues (n = 17) were obtained from the Gene Expression Omnibus. Differentially
      expressed genes (DEGs), differentially methylated regions (DMRs) and CpG islands
      (DMIs) were identified and compared. Pathway enrichment analysis was performed,
      and the functional interactions were investigated. RESULTS: A total of 392 DEGs,
      2667 DMRs, and 464 DMIs were found between the two groups, and a functional
      interaction network of DEGs was established. Then, 28 potential key genes were
      identified, which were oppositely regulated in preeclampsia regarding expression
      and methylation. Eight of the potential key genes had DMIs, among which ITGA5
      interacted with FN1 and FOS. The 3 DEGs were up-regulated, and their DMIs were
      hypomethylated. CONCLUSION: FN1, FOS, and ITGA5 might promote the development of
      preeclampsia via modulating differentiation/apoptosis/invasion of human
      extravillous trophoblasts, as well as focal adhesion, VEGFR3 signaling, beta1
      integrin cell surface interactions, alpha9beta1/alpha4beta1 integrin signaling,
      AP-1/ATF-2/HIF-1alpha transcription factor networks, and Fc-epsilon receptor I
      signaling in mast cells.

PMID- 29039999
TI  - Treatment and survival of childhood neuroblastoma: Evidence from a population
      based study in the United States.
AB  - BACKGROUND: Childhood neuroblastoma describes a heterogeneous group of
      extracranial solid tumors, that are treated per risk profile. We sought to
      describe treatment patterns and survival using population-based data from
      throughout the United States. MATERIALS AND METHODS: Using the National Cancer
      Institute (NCI)'s Patterns of Care data, we analyzed treatment provided to newly
      diagnosed, histologically confirmed neuroblastoma patients in 2010 and 2011,
      registered to one of 14 Surveillance, Epidemiology, and End Results (SEER) cancer
      registries. Data were re-abstracted from hospital records and treating physicians
      contacted for verification. Application of the Children's Oncology Group (COG)'s
      3-level (low, intermediate and high) neuroblastoma risk classification system for
      therapeutic decision-making provided insight to community-based treatment
      patterns. Kaplan-Meier survival analyses, based on 5-years of follow-up, were
      also performed. RESULTS: 76% of the 250 patients were enrolled on an open/active
      clinical trial. All low-risk patients received surgery. Most intermediate-risk
      patients (81%) received a chemotherapy regimen that included carboplatin,
      etoposide, cyclophosphamide and doxorubicin. High-risk patients received
      extensive, multimodal treatment consisting of chemotherapy, surgery,
      myeloablative chemotherapy with stem cell rescue (transplant), radiation,
      immunotherapy (dinutuximab), and isotretinoin therapy. 21% patients had died at
      the end of the maximum 60-month follow-up period. The 5-year estimated survival
      rates were lower for patients diagnosed with stage 4 disease, unfavorable DNA
      ploidy, MYCN gene amplification or classified as high-risk. CONCLUSION: Most
      neuroblastoma patients are registered on a risk-based open/active clinical trial.
      Variation in modality, systemic agents and sequence of treatment reflects the
      heterogeneity of therapy received by these patients.

PMID- 29040000
TI  - Methionine Induces LAT1 Expression in Dairy Cow Mammary Gland by Activating the
      mTORC1 Signaling Pathway.
AB  - Methionine is the limiting amino acid for milk protein synthesis in dairy cows.
      The effect of methionine availability on milk protein synthesis is dependent on
      its active transport into cells through amino acid transporters. L-type amino
      acid transporter 1 (LAT1), which induces the transport of neutral amino acids, is
      highly expressed in lactating mammary gland. However, the effect of methionine on
      LAT1 expression and the mechanism governing this process in dairy cow mammary
      gland are poorly understood. In this study, we show that treatment of dairy cow
      mammary epithelial cells with increasing concentrations of methionine for 24 h
      resulted in increased expression of LAT1 and its associated protein 4F2 heavy
      chain (4F2hc). Maximal expression levels occurred after treatment with 0.6 mM
      methionine. Methionine treatment also increased cell viability and beta-casein
      synthesis. Western blots showed that methionine induced LAT1 and 4F2hc expression
      by activating mammalian target of rapamycin complex 1 (mTORC1) signaling.
      Inhibition of mTORC1 signaling by rapamycin or raptor siRNA prevented the
      upregulation of LAT1 and 4F2hc. These results indicate that methionine may
      activate the mTORC1 signaling pathway and further increase LAT1 and 4F2hc
      expression in dairy cow mammary gland, thus affecting milk protein synthesis.

PMID- 29040001
TI  - Is gastroesophageal reflux disease associated with primary acquired nasolacrimal
      duct obstruction?
AB  - PURPOSE: To determine if patients with primary acquired nasolacrimal duct
      obstruction (PANDO) have an increased prevalence of gastroesophageal reflux
      disease (GERD) compared to the general population. METHODS: Cross-sectional case
      control study. The Mayo Clinic Reflux Disease Questionnaire (RDQ) is used to help
      physicians diagnose GERD. The retrospective group consisted of patients who
      previously had a dacryocystorhinostomy (DCR) over a 4-year period by one surgeon
      (JTH) at one institution. The prospective group included consecutive patients
      undergoing DCR over an 8-month period for PANDO. The control group consisted of
      patients at our institution who did not have complaints related to nasolacrimal
      duct obstruction (NLDO) or a known history of NLDO. The RDQ score or a previous
      diagnosis of GERD was recorded for each patient. The prevalence of patients with
      GERD in each of the groups was compared to that in the control group using the
      Fisher exact test. RESULTS: Nine (7.7%) of 117 patients in the control group were
      found to have GERD. Twenty-four of 65 (36.9%) patients in the retrospective
      cohort were found to have GERD. Twelve of 18 (66.7%) patients in the prospective
      cohort were found to have GERD. When the prospective and retrospective groups
      were compared to the control group, the presence of GERD was higher in patients
      with NLDO (p < .0001). CONCLUSION: Based on the results of this study and
      compared to the general population, GERD has an increased prevalence in patients
      with PANDO. GERD may have a role in the development of PANDO.

PMID- 29040002
TI  - FAK-Src-paxillin system expression and disease outcome in human neuroblastoma.
AB  - BACKGROUND: Neuroblastoma (NB) often presents with metastatic disease and poor
      survival. The need for new prognostic markers remains invaluable. The FAK-Src
      Paxillin protein system is associated with aggressive phenotype in adult
      malignancies but is largely unexplored in pediatric NB. OBJECTIVE: To assess FAK
      Src-Paxillin protein expression in human NB cell lines and clinical cytology
      material and to delineate its association with survival. DESIGN/METHODS: Western
      blot and immunohistochemistry were applied for FAK-Src-Paxillin expression in NB
      cell lines and 23 human cytology specimens, respectively. Protein expression in
      human clinical samples was correlated with clinicopathological parameters, MYCN
      amplification and survival. RESULTS: FAK, Src and Paxillin proteins are expressed
      in human NB cells lines, and can be detected in clinical cytology specimens from
      NB patients, (59%, 32% and 33% respectively). Simultaneous FAK-Src-Paxillin
      expression was noted in 30% of NB patients. Children with concomitant positivity
      FAK, Src, and Paxillin tumors, as well as MYCN amplification, had increased
      mortality compared to those without. CONCLUSIONS: FAK-Src-Paxillin system is a
      marker of unfavorable prognosis for human NB patients but also a promising
      therapeutic target.

PMID- 29040003
TI  - Dietary risk evaluation for 28 polycyclic aromatic hydrocarbons (PAHs) in tea
      preparations made of teas available on the Polish retail market.
AB  - The aim of this work was to assess dietary risk resulting from consumption of
      polycyclic aromatic hydrocarbons (PAHs) with tea infusions. To this end, levels
      of 28 PAHs in black, green, red and white teas available on the Polish retail
      market have been assessed. Profiles and correlation between concentrations of
      individual PAHs have been identified. A model study on transfer of PAHs from tea
      leaves into tea preparations has been conducted. Relatively high concentrations
      of 28 evaluated PAHs have been found in 58 tested samples of black, green, red
      and white teas sampled on the Polish retail market. Total concentration ?28PAH
      ranged from 57 to 696 ug kg-1 with mean 258 ug kg-1 (dry tea leaves). The most
      mature tea leaves fermented to a small degree contained relatively the highest
      PAH levels among all four tested tea types. Relatively low PAH transfer rates
      into tea infusions and limited volumes of the consumed tea keep the risks
      associated with PAH dietary intake at a safely low level. The worst-case scenario
      dietary intake values were 7.62/0.82/0.097 ng kg-1 b.w. day-1 (estimated on the
      basis of the maximum found concentrations 696/113/23 ug kg-1 and maximum observed
      transfer rates 24/16/9%) for ?28PAH/?PAH4/B[a]P, respectively. MOE values
      calculated using the above worst case estimates exceeded 700,000 and 400,000
      (BMDL10 0.07 and 0.34 mg kg-1 b.w. day-1) for B[a]P and PAH4, respectively. Both
      B[a]P and PAH4 concentrations may be used as indicators of total PAH
      concentration in tea leaves; PAH4 slightly better fits low molecular weight PAHs.
      Several correlations between various PAHs/groups of PAHs have been identified,
      the strongest one (R2 = 0.92) between PAH4 and EU PAH 15+1.

PMID- 29040004
TI  - Building Bridges: A Case for Community Health Worker Provision of Misoprostol
      Only Abortion in the First Trimester.
AB  - INTRODUCTION: The consequences of unsafe abortion are devastating to women, their
      families, and their communities. Medication abortion presents an important
      alternative to harmful self-induction practices and surgical intervention under
      questionable circumstances. In settings where mifepristone is unavailable, the
      use of misoprostol alone is a safe and effective option for terminating an
      unwanted pregnancy. Studies have demonstrated the safety and efficacy of
      administration of misoprostol by community health workers (CHW) for indications
      such as postpartum hemorrhage and treatment of incomplete abortion. OBJECTIVES:
      The current study assesses the safety and efficacy of CHW managing misoprostol
      only abortion in the first trimester. METHODS: A retrospective review of clinical
      files of women who received abortion services in three countries in Latin America
      between April 2009 and December 2015 included analysis of 173 cases. RESULTS: In
      94% of cases, the pregnancy was terminated without any further intervention. In
      the remaining cases, clients were referred for manual vacuum aspiration. In four
      cases, a complication was reported by the provider. In one, the complication was
      promptly resolved through referral to a higher level of care; in the remaining
      three, the complication was resolved directly by the provider. In 98% of cases,
      women reported being satisfied with the treatment they received. CONCLUSION: This
      study demonstrates that CHW are able to provide misoprostol-only abortion
      services to women effectively and safely. The benefits of this model of care also
      extend beyond the abortion service: CHW are able to offer women a comprehensive
      range of quality health services, including contraceptive services, increasing
      access to vital healthcare in areas with few other options.

PMID- 29040005
TI  - The Shape of Vesicle-Containing Organelles Is Critical for Their Functions in
      Vesicle Endocytosis.
AB  - Exosomes are small vesicles secreted by a variety of cell types under
      physiological and pathological conditions. When Saccharomyces cerevisiae are
      grown in low glucose, small vesicles carrying more than 300 proteins with diverse
      biological functions are secreted. Upon glucose addition, secreted vesicles are
      endocytosed that requires cup-shaped organelles containing the major eisosome
      protein Pil1p at the rims. We aim to identify genes that regulate the function of
      cup-shaped organelles in vesicle endocytosis. In cells lacking either VID27 or
      VID21, Pil1p distribution was altered and cup-shaped organelles became elongated
      with narrower openings. Change in shape reduced the number of vesicles in the
      deeper areas and impaired vesicle endocytosis. Vid21p and Vid27p were localized
      to vesicle clusters and interacted with other Vid proteins. In the absence of
      these genes, these vesicles failed to aggregate and were secreted. Vid21p and
      Vid27p are required for the aggregation and retention of vesicles that contain
      Vid proteins in the cytoplasm. Increased vesicles near the plasma membrane in
      mutant strains correlate with an increased Pil1p movement resulting in the fusion
      of cup-shaped organelles. We conclude that the shape of vesicle-containing
      organelles is critical for their functions in vesicle endocytosis.

PMID- 29040006
TI  - Neurokinin 3 receptor antagonism - the magic bullet for hot flushes?
AB  - Hot flushes affect 70% of menopausal women and are reported as being the most
      bothersome symptom by the majority. Hormone replacement therapy and other
      currently available alternative therapies are not without side-effects and/or
      have variable efficacy, and so an effective novel therapy could be practice
      changing. Over the last 20 years, numerous studies in animal and human models
      have implicated neurokinin B, a hypothalamic neuropeptide, together with its
      receptor (NK3R) in the etiology of menopausal hot flushes. Most recently, a
      randomized, placebo-controlled trial of an NK3R antagonist in symptomatic
      menopausal women has proven concept suggesting a new therapeutic that can safely
      and effectively reduce hot flush frequency, severity, bother, and interference
      without the need for estrogen exposure. Here we review the physiology and
      neurocircuitry of the reproductive axis, hot flushes, and the evidence that
      supports this potential new therapeutic approach.

PMID- 29040007
TI  - Probing Birth-Order Effects on Narrow Traits Using Specification-Curve Analysis.
AB  - The idea that birth-order position has a lasting impact on personality has been
      discussed for the past 100 years. Recent large-scale studies have indicated that
      birth-order effects on the Big Five personality traits are negligible. In the
      current study, we examined a variety of more narrow personality traits in a large
      representative sample ( n = 6,500-10,500 in between-family analyses; n = 900
      1,200 in within-family analyses). We used specification-curve analysis to assess
      evidence for birth-order effects across a range of models implementing defensible
      yet arbitrary analytical decisions (e.g., whether to control for age effects or
      to exclude participants on the basis of sibling spacing). Although specification
      curve analysis clearly confirmed the previously reported birth-order effect on
      intellect, we found no meaningful effects on life satisfaction, locus of control,
      interpersonal trust, reciprocity, risk taking, patience, impulsivity, or
      political orientation. The lack of meaningful birth-order effects on self-reports
      of personality was not limited to broad traits but also held for more narrowly
      defined characteristics.

PMID- 29040008
TI  - Analysis of the Clinical Profile and Management of Inflammatory Choriodal
      Neovascular Membranes in Uveitic Eyes: A Study from A Tertiary Referral Center.
AB  - PURPOSE: To analyze clinical profile and management of inflammatory choroidal
      neovascularization (CNV) seen at a referral uveitis clinic. METHODS: Records of
      patients with uveitis and inflammatory CNV from January 1989 to April 2012 were
      retrieved and the data was analyzed. RESULTS: Forty-nine eyes of 43 patients were
      included. Mean age at presentation was 35.81 years. Eighteen eyes (36.7%) had
      infective etiology and 31 eyes (63.2%) had non-infective etiology. The most
      common location of the CNV was subfoveal, in 18 eyes (36.7%). Management included
      corticosteroids in all patients, additional immunosuppressive in 17 eyes (34.6%)
      and local management, with anti-VEGF injections in 29 eyes (63%). Visual outcome
      was favorable in 37 eyes (75%). CONCLUSION: Inflammatory CNV can be successfully
      managed and vision can be improved or stabilized, with prompt and adequate
      therapy of the underlying uveitic disease coupled with additional local therapy
      to selectively target the CNV.

PMID- 29040009
TI  - Ocular Involvement in Patients with Fungemia in an Urban Tertiary Care Center.
AB  - PURPOSE: To illustrate the rate of endogenous endophthalmitis associated with
      fungemia and evaluate the importance of screening in a public city hospital.
      METHODS: A retrospective review was performed on all inpatient ophthalmology
      consults for fungemia from 2010 to 2015. Clinical histories, ocular examinations,
      and microbial cultures were reviewed. RESULTS: Of 95 patients (mean age 51.6
      years, 75% male) with fungemia, 9/95 (9.5%) demonstrated intraocular involvement.
      Of these nine patients, two were unable to participate in the ophthalmic exam due
      to intubation, while the remaining seven reported no changes in their vision. Two
      patients had their antifungal medications adjusted to optimize intraocular
      penetration and one patient progressed to develop vitreous involvement but died
      before further escalation of care occurred. CONCLUSION: All involved individuals
      in this study were either non-communicative or without visual complaints. This
      suggests that routine screening should still be recommended, especially in a
      public hospital setting.

PMID- 29040011
TI  - Bioactive edible films for food applications:Influence of the bioactive compounds
      on film structure and properties.
AB  - Nowadays, a new generation of edible films is being especially designed for
      incorporating antimicrobials, antioxidants, enzymes or functional ingredients.
      Edible films made from natural biopolymers become the focus of many research
      works as an alternative to synthetic food packaging due to their edibility,
      biodegradability and compostability as well as to their use as active packaging.
      Active compounds incorporated in edible films could protect foods against
      deterioration during storage and therefore extend their shelf life. These active
      films were mainly studied for the bioactivity, as antimicrobial or antioxidant.
      However, they could also improve the structure and the physicochemical properties
      of films through chemical linkage with reactive groups of the polymer chains for
      instance. Moreover, changing the film structure under cross-linking reaction may
      increase the cohesion between polymer chains and active compounds, and therefore
      their retention in the polymer network to better control their release. This
      manuscript provides an overview on the effect of bio-active compounds
      incorporation on the film structure and functional properties. Depending on their
      structure, concentration, reactive groups,.., active compounds can act as
      plasticizer, but also as anti-plasticizer or cross-linking agents in the
      biopolymer matrix, and can thus ameliorate the water vapour and gas permeability.
      Therefore, the retention of bioactive compounds in the polymer network and their
      release can be better controlled. They can also provide a negative plasticizing
      effect on the film structure. Hence, the improvement of edible active film
      functionalities has been investigated to achieve suitable applications on foods.

PMID- 29040013
TI  - Connectome-based Models Predict Separable Components of Attention in Novel
      Individuals.
AB  - Although we typically talk about attention as a single process, it comprises
      multiple independent components. But what are these components, and how are they
      represented in the functional organization of the brain? To investigate whether
      long-studied components of attention are reflected in the brain's intrinsic
      functional organization, here we apply connectome-based predictive modeling (CPM)
      to predict the components of Posner and Petersen's influential model of
      attention: alerting (preparing and maintaining alertness and vigilance),
      orienting (directing attention to a stimulus), and executive control (detecting
      and resolving cognitive conflict) [Posner, M. I., & Petersen, S. E. The attention
      system of the human brain. Annual Review of Neuroscience, 13, 25-42, 1990].
      Participants performed the Attention Network Task (ANT), which measures these
      three factors, and rested during fMRI scanning. CPMs tested with leave-one
      subject-out cross-validation successfully predicted novel individual's overall
      ANT accuracy, RT variability, and executive control scores from functional
      connectivity observed during ANT performance. CPMs also generalized to predict
      participants' alerting scores from their resting-state functional connectivity
      alone, demonstrating that connectivity patterns observed in the absence of an
      explicit task contain a signature of the ability to prepare for an upcoming
      stimulus. Suggesting that significant variance in ANT performance is also
      explained by an overall sustained attention factor, the sustained attention CPM,
      a model defined in prior work to predict sustained attentional abilities,
      predicted accuracy, RT variability, and executive control from task-based data
      and predicted RT variability from resting-state data. Our results suggest that,
      whereas executive control may be closely related to sustained attention, the
      infrastructure that supports alerting is distinct and can be measured at rest. In
      the future, CPM may be applied to elucidate additional independent components of
      attention and relationships between the functional brain networks that predict
      them.

PMID- 29040012
TI  - Outcome of acute lymphoblastic leukemia in children with down syndrome-Polish
      pediatric leukemia and lymphoma study group report.
AB  - Children with Down syndrome (DS) have a 20-fold increased risk of developing
      leukemia compared with the general population. The aim of the study was to
      analyze the outcome of patients diagnosed with Down syndrome and acute
      lymphoblastic leukemia (ALL) in Poland between the years 2003 and 2010. A total
      of 1848 children were diagnosed with ALL (810 females and 1038 males). Of those,
      41 (2.2%) had DS. The children were classified into three risk groups: a standard
      risk group-14 patients, an intermediate-risk group-24, a high-risk group-3. All
      patients were treated according to ALLIC 2002 protocol. The median observation
      time of all patients was 6.1 years, and in patients with DS 5.3 years. Five-year
      overall survival (OS) was the same in all patients (86% vs 86%, long-rank test, p
      = .9). The relapse-free survival (RFS) was calculated as 73% in patients with DS
      and 81% in patients without DS during a median observation time (long-rank test,
      p = .3). No statistically significant differences were found in the incidence of
      nonrelapse mortality between those two groups of patients (p = .72). The study
      was based on children with ALL and Down syndrome who were treated with an
      identical therapy schedule as ALL patients without DS, according to risk group.
      This fact can increase the value of the presented results.

PMID- 29040015
TI  - Distinct Representations of Magnitude and Spatial Position within Parietal Cortex
      during Number-Space Mapping.
AB  - Mapping numbers onto space is foundational to mathematical cognition. These
      cognitive operations are often conceptualized in the context of a "mental number
      line" and involve multiple brain regions in or near the intraparietal sulcus
      (IPS) that have been implicated both in numeral and spatial cognition. Here we
      examine possible differentiation of function within these brain areas in relating
      numbers to spatial positions. By isolating the planning phase of a number line
      task and introducing spatiotopic mapping tools from fMRI into mental number line
      task research, we are able to focus our analysis on the neural activity of areas
      in anterior IPS (aIPS) previously associated with number processing and on
      spatiotopically organized areas in and around posterior IPS (pIPS), while
      participants prepare to place a number on a number line. Our results support the
      view that the nonpositional magnitude of a numerical symbol is coded in aIPS,
      whereas the position of a number in space is coded in posterior areas of IPS. By
      focusing on the planning phase, we are able to isolate activation related to the
      cognitive, rather than the sensory-motor, aspects of the task. Also, to allow the
      separation of spatial position from magnitude, we tested both a standard positive
      number line (0 to 100) and a zero-centered mixed number line (-100 to 100). We
      found evidence of a functional dissociation between aIPS and pIPS: Activity in
      aIPS was associated with a landmark distance effect not modulated by spatial
      position, whereas activity in pIPS revealed a contralateral preference effect.

PMID- 29040014
TI  - Spatially Selective Alpha Oscillations Reveal Moment-by-Moment Trade-offs between
      Working Memory and Attention.
AB  - Current theories assume a functional role for covert attention in the maintenance
      of spatial information in working memory. Consistent with this view, both the
      locus of attention and positions stored in working memory can be decoded based on
      the topography of oscillatory alpha-band (8-12 Hz) activity on the scalp. Thus
      far, however, alpha modulation has been studied in isolation for covert attention
      and working memory tasks. Here, we applied an inverted spatial encoding model in
      combination with EEG to study the temporal dynamics of spatially specific alpha
      activity during a task that required observers to visually select a target
      location while maintaining another independently varying location in working
      memory. During the memory delay period, alpha-based spatial tuning functions
      shifted from the position stored in working memory to the covertly attended
      position and back again after the attention task was completed. The findings
      provide further evidence for a common oscillatory mechanism in both the selection
      and the maintenance of relevant spatial visual information and demonstrate the
      dynamic trade-off in prioritization between two spatial tasks.

PMID- 29040010
TI  - Deregulated angiogenesis in chronic lung diseases: a possible role for lung
      mesenchymal progenitor cells (2017 Grover Conference Series).
AB  - Chronic lung disease (CLD), including pulmonary fibrosis (PF) and chronic
      obstructive pulmonary disease (COPD), is the fourth leading cause of mortality
      worldwide. Both are debilitating pathologies that impede overall tissue function.
      A common co-morbidity in CLD is vasculopathy, characterized by deregulated
      angiogenesis, remodeling, and loss of microvessels. This substantially worsens
      prognosis and limits survival, with most current therapeutic strategies being
      largely palliative. The relevance of angiogenesis, both capillary and lymph, to
      the pathophysiology of CLD has not been resolved as conflicting evidence depicts
      angiogenesis as both reparative or pathologic. Therefore, we must begin to
      understand and model the underlying pathobiology of pulmonary vascular
      deregulation, alone and in response to injury induced disease, to define cell
      interactions necessary to maintain normal function and promote repair. Capillary
      and lymphangiogenesis are deregulated in both PF and COPD, although the
      mechanisms by which they co-regulate and underlie early pathogenesis of disease
      are unknown. The cell-specific mechanisms that regulate lung vascular
      homeostasis, repair, and remodeling represent a significant gap in knowledge,
      which presents an opportunity to develop targeted therapies. We have shown that
      that ABCG2pos multipotent adult mesenchymal stem or progenitor cells (MPC)
      influence the function of the capillary microvasculature as well as
      lymphangiogenesis. A balance of both is required for normal tissue homeostasis
      and repair. Our current models suggest that when lymph and capillary angiogenesis
      are out of balance, the non-equivalence appears to support the progression of
      disease and tissue remodeling. The angiogenic regulatory mechanisms underlying
      CLD likely impact other interstitial lung diseases, tuberous sclerosis, and
      lymphangioleiomyomatosis.

PMID- 29040016
TI  - Centella asiatica Fraction-3 Suppresses the Nuclear Factor Erythroid 2-Related
      Factor 2 Anti-Oxidant Pathway and Enhances Reactive Oxygen Species-Mediated Cell
      Death in Cancerous Lung A549 Cells.
AB  - Centella asiatica is a tropical medicinal plant that is commonly used in
      traditional medicine. Medicinal properties of C. asiatica include anti-oxidant,
      anti-inflammatory, and anti-cancer activity. We investigated the anti-oxidant and
      anti-proliferative/cytotoxic effects of a semi-purified fraction of C. asiatica
      ethanolic leaf extract (C3) in cancerous lung A549 cells. C3 was obtained by
      silica column fractionation and identified by using thin-layer chromatography and
      gas chromatography mass spectrometry. Cytotoxicity of C3 in A549 cells was
      evaluated (cell viability assay-WST-1; 24 h; [0.2-3 mg/mL]) to determine an
      inhibitory concentration (IC50). Intracellular reactive oxygen species (IROS),
      mitochondrial membrane potential (flow cytometry), malondialdehyde (MDA), lactate
      dehydrogenase (LDH) (spectrophotometry), glutathione (GSH), oxidised glutathione
      (GSSG), adenosine triphosphate levels, caspase activity (luminometry), and DNA
      damage (comet assay) were evaluated. Protein expression (Nrf-2, p53, Bax, Bcl-2,
      and HSP-70) and gene expression (Nrf-2, GPx, SOD, CAT, c-myc, and OGG-1) were
      quantified by western blotting and quantitative polymerase chain reaction (qPCR),
      respectively. C3 dose dependently decreased A549 cell viability. The IC50 of C3
      increased MDA, IROS, mitochondrial depolarization, LDH, caspase (-8, -9, -3/7)
      activity, DNA damage, GSH levels, Nrf-2 protein expression, HSP-70 protein
      expression, and OGG-1 gene expression (P < .05). GSSG levels, anti-oxidant (Nrf
      2, GPx, SOD) gene expression, p53, Bax, and Bcl-2 protein expression were
      decreased by C3 (P < .02). C3 diminished the anti-oxidant gene expression and
      induced anti-proliferative/cytotoxic effects in A549 cells.

PMID- 29040017
TI  - Aralia elata (Miq) Seem Extract Decreases O-GlcNAc Transferase Expression and
      Retinal Cell Death in Diabetic Mice.
AB  - Aralia elata (Miq) Seem (AES) is a medicinal plant used in traditional Chinese
      and Korean medicine for the treatment of several diseases, including diabetes.
      This study aimed to investigate the neuroprotective effect of AES extract against
      high glucose-induced retinal injury in diabetic mice. AES extract (20 and 100
      mg/kg body weight) was orally administered to control mice or mice with
      streptozotocin-induced diabetes. Protein levels of O-linked beta-N
      acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element
      binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1,
      thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl
      CoA carboxylase (ACC) were analyzed by western blotting. Colocalization of
      terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)
      positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double
      immunofluorescence analysis. Interaction between ChREBP and OGT was assessed
      using coimmunoprecipitation analysis. AES extract protected the retinas from
      neuronal injury and decreased levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC
      in the diabetic retinas. AES extract reduced colocalization of TUNEL-positive
      ganglion cells and OGT, ChREBP, or TXNIP in the diabetic retinas.
      Coimmunoprecipitation analysis indicated that AES extract reduced interaction
      between ChREBP and OGT and attenuated ganglion cell death in diabetic retinas.
      Moreover, the ChREBP that colocalized with OGT or the TUNEL signal was
      significantly decreased in diabetic mice treated with AES extract. These findings
      show that AES extract can alleviate OGT-, ChREBP-, TXNIP-, or SREBP-1-related
      retinal injury in diabetic retinopathy.

PMID- 29040018
TI  - Primary Abdominal Wall Abscess by Actinomyces and Eikenella corrodens: A First
      Report.

PMID- 29040019
TI  - Seasonal expression patterns of clock-associated genes in the blue mussel Mytilus
      edulis.
AB  - Environmental cues allow organisms to synchronise their internal biological
      rhythms with external environmental cycles. These rhythms are regulated on a
      molecular level by oscillating interactions between clock genes and their
      proteins. Light is a particularly relevant environmental cue, provisioning daily
      information via light/dark cycles as well as seasonal information via day-length
      (photoperiod). Despite the ecological and commercial importance of bivalves,
      little is known about the interactions comprising their molecular clock
      mechanism. This study investigates the link between the annual seasonal
      progression and reproductive development in the blue mussel (Mytilus edulis),
      using mRNA expression patterns of clock-associated genes: Clock, Cry1  ARNT,
      Timeout-like, ROR/HR3 and aaNAT, in the gonads of both sexes, sampled over three
      daily time-points on a tidal beach during the winter and summer solstices.
      Significant differences in mRNA expression levels, including some seasonal
      differences at comparable time-points, were detected for all genes with the
      exception of Timeout-like. These differences occurred seasonally within sex
      (Clock, Cry1, ROR/HR3), seasonally between sexes (Clock, Cry1, ARNT, ROR/HR3,
      aaNAT) and daily between sexes (Cry1), although no significant daily differences
      were detected in summer or winter for either sex for any of the genes. This study
      reveals that clock-associated genes show seasonal responses in this species of
      bivalve. Understanding the mechanisms by which environmental cues drive
      biological rhythms is critical to understanding the seasonal sensitivity of this
      keystone species to environmental changes.

PMID- 29040021
TI  - Flexible Sigmoidoscopy and CT Colonography Screening: Patients' Experience with
      and Factors for Undergoing Screening-Insight from the Proteus Colon Trial.
AB  - Purpose To compare the acceptability of computed tomographic (CT) colonography
      and flexible sigmoidoscopy (FS) screening and the factors predicting CT
      colonographic screening participation, targeting participants in a randomized
      screening trial. Materials and Methods Eligible individuals aged 58 years (n =
      1984) living in Turin, Italy, were randomly assigned to be invited to screening
      for colorectal cancer with FS or CT colonography. After individuals who had died
      or moved away (n = 28) were excluded, 264 of 976 (27.0%) underwent screening with
      FS and 298 of 980 (30.4%) underwent CT colonography. All attendees and a sample
      of CT colonography nonattendees (n = 299) were contacted for a telephone
      interview 3-6 months after invitation for screening, and screening experience and
      factors affecting participation were investigated. Odds ratios (ORs) were
      computed by means of multivariable logistic regression. Results For the telephone
      interviews, 239 of 264 (90.6%) FS attendees, 237 of 298 (79.5%) CT colonography
      attendees, and 182 of 299 (60.9%) CT colonography nonattendees responded. The
      percentage of attendees who would recommend the test to friends or relatives was
      99.1% among FS and 93.3% among CT colonography attendees. Discomfort associated
      with bowel preparation was higher among CT colonography than FS attendees (OR,
      2.77; 95% confidence interval [CI]: 1.47, 5.24). CT colonography nonattendees
      were less likely to be men (OR, 0.36; 95% CI: 0.18, 0.71), retired (OR, 0.31; 95%
      CI: 0.13, 0.75), to report regular physical activity (OR, 0.37; 95% CI: 0.20,
      0.70), or to have read the information leaflet (OR, 0.18; 95% CI: 0.08, 0.41).
      They were more likely to mention screening-related anxiety (mild: OR, 6.30; 95%
      CI: 2.48, 15.97; moderate or severe: OR, 3.63; 95% CI: 1.87, 7.04), erroneous
      beliefs about screening (OR, 32.15; 95% CI: 6.26, 165.19), or having undergone a
      recent fecal occult blood test (OR, 13.69; 95% CI: 3.66, 51.29). Conclusion CT
      colonography and FS screening are well accepted, but further reducing the
      discomfort from bowel preparation may increase CT colonography screening
      acceptability. Negative attitudes, erroneous beliefs about screening, and
      organizational barriers are limiting screening uptake; all these factors are
      modifiable and therefore potentially susceptible to interventions. (c) RSNA, 2017
      Online supplemental material is available for this article.

PMID- 29040020
TI  - First Report of Toxoplasma gondii Infection in Tuberculosis Patients in China.
AB  - In recent years, coinfection of tuberculosis (TB) and parasitosis in humans is an
      emerging problem in coendemic areas, which has been increasingly highlighted in
      developing countries. However, there is limited information about the prevalence
      of Toxoplasma gondii infection in TB patients. Therefore, through a case-control
      study, 924 TB patients hospitalized for diacrisis or treatment in northeastern
      and eastern China, and 924 control subjects from the general population of the
      same region matched with gender, age, and residence were examined for the
      presence of IgG and IgM antibodies to T. gondii and associated sociodemographic
      and behavioral characteristics in a population of TB patients. Seroprevalence of
      IgG antibodies to T. gondii in TB patients (122/924, 13.2%) was significantly
      higher than control subjects (90/924, 9.7%) (p = 0.019), and 26 (2.8%) TB
      patients and 19 (2.1%) controls were positive for anti-T. gondii IgM antibodies
      (p = 0.291), respectively. Multivariate analysis showed that T. gondii infection
      was associated with keeping cats at home, presence of stray cats, and consumption
      of raw/undercooked meat. The present study first revealed the seroprevalence of
      T. gondii infection in TB patients in China. Moreover, parasitological surveys
      should be regularly carried out among TB patients, aiming to prevent the
      possibility of severe toxoplasmosis.

PMID- 29040022
TI  - Added Value of a Single Fast 20-second Deep-Inspiration Breath-hold Acquisition
      in FDG PET/CT in the Assessment of Lung Nodules.
AB  - Purpose To compare the accuracy of a single 20-second deep-inspiration breath
      hold (DIBH) in fluorodeoxyglucose (FDG) positron emission tomography
      (PET)/computed tomography (CT) to that with conventional free-breathing (FB)
      whole-body PET/CT for the assessment, characterization, and quantification of
      lung lesions in terms of the blurring effect of respiratory motion. Materials and
      Methods Institutional review board approval was obtained, and the requirement to
      obtain informed consent was waived. A preclinical study was performed in a test
      population of 19 patients to evaluate the feasibility and consistency of DIBH
      techniques compared with phase-based respiratory gating (PBRG). One hundred
      fifteen patients with lung lesions were then prospectively included and assessed
      with FB PET/CT followed by 20-second DIBH PET/CT. Maximum standardized uptake
      value (SUVmax), peak standardized uptake value (SUVpeak), and number and size of
      nodules were reported for each acquisition and then compared with findings from
      histopathologic examination and/or clinical-radiologic follow-up. Statistical
      analysis was performed with the t test, chi2 test, Pearson correlation
      coefficient, and receiver operating characteristic analysis. Results In the test
      population, data obtained with DIBH PET and PBRG PET showed close correlation (r
      = 0.94, P < .001 for SUVmax and r = 0.98, P < .001 for SUVpeak). In the clinical
      population, both SUVmax and SUVpeak were significantly increased with DIBH
      compared with FB (5.60 +/- 4.20 vs 3.11 +/- 1.80 and 2.25 +/- 1.75 vs 1.71 +/-
      0.96, respectively; P < .001). A significantly greater number of lung lesions was
      detected with DIBH PET/CT compared with FB PET/CT (P < .001), with the detection
      of 70 additional nodules and more accurate coregistration of 84. According to the
      area under the receiver operating characteristic curve for SUVpeak, DIBH
      demonstrated a higher level of accuracy than did FB (P = .039). Conclusion The
      DIBH PET/CT technique is feasible in routine clinical practice and is more
      sensitive for quantitative measurements and lesion localization. This technique
      reduces the blurring effect of respiratory motion, thus improving the diagnostic
      accuracy for lung nodules. (c) RSNA, 2017.

PMID- 29040023
TI  - Dramatic clinical and radiographic response to BRAF inhibition in a patient with
      progressive disseminated optic pathway glioma refractory to MEK inhibition.
AB  - While clinical and radiographic responses to agents targeting the mitogen
      activated protein kinases (MAPK) pathway have been repor-ted in pediatric low
      grade gliomas (LGG), early phase trials indicate refractoriness to these
      medications in some of these patients. We report a patient with disseminated LGG
      with the BRAFV600E mutation, which was refractory to selumetinib, a MEK
      inhibitor, but subsequently showed immediate clinical and radiographic response
      to dabrafenib, a BRAF inhibitor, with sustained effect for 9 months prior to
      clinical progression. In LGGs, treatment resistance to one agent targeting the
      MAPK pathway might not imply refractoriness to other agents targeting this
      pathway.

PMID- 29040025
TI  - Effect of chronic consumption of pistachios (Pistacia vera L.) on glucose
      metabolism in pre-diabetics and type 2 diabetics: A systematic review.
AB  - Pistachio is a nut with high polyunsaturated fatty acids (PUFA), monounsaturated
      fatty acids (MUFA), polyphenols and carotenoids content, and the synergism
      between these compounds appears to affect glucose metabolism. In this systematic
      review we analyzed studies in which the effect of chronic consumption of
      pistachio on markers of glucose metabolism was evaluated in pre-diabetic and type
      2 diabetics. We used the PubMed, Scopus, Cochrane and Lilacs databases. The
      research terms used were pistachio, pre-diabetes, type 2 diabetes mellitus,
      insulin resistance, blood glucose, hyperglycemia and glycated hemoglobin (HbA1c).
      Four articles were selected, of which three tested the intake of 50 to 57 g of
      pistachio/day and one 20% of the daily caloric intake, for a period of 1 to 4
      months. Studies reported a decrease in fasting blood glucose, insulinemia, HOMA
      IR, and fructosamine, but no change in HbA1c. Lower concentrations of miR-192 and
      miR-375 were also found, which correlated positively with HOMA-IR. The synergism
      between PUFA, MUFA, polyphenols and carotenoids present in pistachios can
      modulate specific miRNA, increasing insulin sensitivity through the PI3K-AKT
      signaling pathway. This modulation can be used as a tool to monitor the response
      to interventions, favoring the prevention and treatment of complications related
      to diabetes.

PMID- 29040026
TI  - A comparison of the success rates of endoscopic-assisted probing in the treatment
      of membranous congenital nasolacrimal duct obstruction between younger and older
      children and its correlation with the thickness of the membrane at the Valve of
      Hasner.
AB  - Congenital nasolacrimal duct obstruction (CNLDO) remains the most common cause of
      epiphora in infants. This retrospective study compares the success rate of nasal
      endoscopic-assisted probing between younger (3 years and below) and older (above
      3 years) children with membranous CNLDO and its correlation with the thickness of
      the membrane at the valve of Hasner. Case records of a total of 38 eyes in 34
      children with membranous CNLDO who underwent endoscopic nasolacrimal duct probing
      and irrigation under general anesthesia were analyzed. The cases were divided
      into two groups, Group Y (20 cases of children 3 years and below) and Group O (18
      cases of children above 3 years). The success of the procedure was defined as
      complete remission of symptoms and a clinical examination of eye to rule out the
      presence for discharge or watering after three months of the procedure. Overall,
      35 cases (92.1%) were successfully treated with a success rate of 95% in Group Y
      and 88.9% in Group O. The mid-P exact test p value for the success rate between
      the two cohorts was not statistically significant (p = 0.59). The thick membrane
      was observed in 50% cases in Group Y and 33.33% cases in Group O (p = 0.34).
      There is no age related decline in the overall success rate for nasal endoscopic
      assisted probing and irrigation in cases of membranous CNLDO. The thickness of
      the membrane may be a factor for failed blind probing, but it has no correlation
      with the success rate if probing is done under endoscopic guidance.

PMID- 29040024
TI  - Permeability and calcium signaling in lung endothelium: unpack the box....
AB  - This brief review assesses the role of Ca2+ signaling in lung endothelium in
      regulation of endothelial permeability. The disconnect between experimental and
      clinical outcomes to date may be due, in part, to the use of tools which yield
      information about aggregate permeability or Ca2+ responses in lung or in
      endothelial monolayers. The teaching point of this review is to "unpack the box,"
      i.e. consider the many potential issues which could impact interpretation of
      outcomes. These include phenotypic heterogeneity and resultant segment-specific
      permeability responses, methodologic issues related to permeability measures,
      contributions from Ca2+ channels in cells other than endothelium-such as alveolar
      macrophages or blood leukocytes), Ca2+ dynamic patterns, rather than averaged
      Ca2+ responses to channel activation, and the background context, such as changes
      in endothelial bioenergetics with sepsis. Any or all of these issues might color
      interpretation of permeability and Ca2+ signaling in lung.

PMID- 29040027
TI  - Touraine-Solente-Gole syndrome.
AB  - Touraine-Solente-Gole syndrome, also known as Pachydermoperiostosis (PDP) or
      Primary Hypertrophic Osteoarthropathy, is a rare hereditary disorder, which
      affects both bones and skin. It is characterized by a combination of dermatologic
      changes (pachydermia or thickening of the skin) and rheumatologic manifestations
      (periostosis and finger clubbing). Eyelid ptosis which is caused by thickened
      eyelids (blepharoptosis) is a less common symptom. We report the case of a
      patient with a complete form of Touraine-Solente-Gole syndrome with bilateral
      blepharoptosis as presenting feature.

PMID- 29040028
TI  - Elaboration in type, primary structure, and bioactivity of polysaccharides
      derived from mollusks.
AB  - Over the past decades, numerous Mollusca species have received more attention in
      development and utilization as valuable bio-resources. Many efforts have been
      focused on investigating mollusk polysaccharides because of their rich content,
      ease of extraction, diversified sorts, specific structure, various biofunctions
      and potent activities. To date, many mollusks, especially species of gastropods,
      bivalves, or cephalopods, have been reported containing polysaccharide compounds
      in tissues with abundant amount, and most of polysaccharides are obtainable
      through combining techniques of extraction, separation and purification. The
      polysaccharides isolated from mollusks appeared with various structural and
      physicochemical characteristics, ranged from neutral polysaccharides and sulfated
      polysaccharides, to GAGs series (including Hep/HS, CS/DS, HA and similarities),
      even to heterogeneous glycan with high molecular weight. This review article
      provides comprehensive knowledge of recent researches on type classification,
      tissue origins and possible biofunctions of various polysaccharides from
      mollusks. The highlights were placed in structure variation including molecular
      weight, sulfation pattern, linkages and monomer compositions for repeating unit,
      and primary molecular construction of the mollusks polysaccharides. In addition,
      this article covers general information on exhibition of mollusks polysaccharide
      extracts or preparations in the various bioactivities, such as anticoagulant,
      antiatherogenic, antioxidant, immunomodulatory, antivirus and antitumor
      activities, which would reveal their possible potentials in medical application.
      Furthermore, the article presents a brief overview on several challenges and
      future scope in this field.

PMID- 29040029
TI  - Autologous fat transfer with SEFFI (superficial enhanced fluid fat injection)
      technique in periocular reconstruction.
AB  - PURPOSE: To evaluate the aesthetic and functional outcomes of autologous fat
      transfer using the SEFFI (superficial enhanced fluid fat injection) technique for
      reconstruction of the periocular area. METHODS: Autologous fat injections
      prepared with the 0.5 mL and 0.8 mL SEFFI technique were used in four patients
      for periocular rehabilitation. RESULTS: Case 1 (C1): A patient with left-sided
      progressive facial hemiatrophy underwent ipsilateral volumizing with 0.8 SEFFI in
      the superior, temporal, and inferior periorbital areas, and 0.5 SEFFI in both
      eyelids. C2: A 21-year-old female with a post trauma frontal scar, left ptosis,
      and lower eyelid retraction was treated with 0.5 SEFFI applied in the scar area
      associated with an upper eyelid conjunctivomullerectomy and resection of the
      lower eyelid retractors. C3: A patient with previous left-eye evisceration and
      orbital floor and medial wall fractures underwent socket reconstruction with
      buccal mucosal graft in the lower fornix and 0.5 SEFFI injections in both
      superior and inferior eyelids. SEFFI was also applied in the intraorbital space
      for correction of the enophthalmos. C4: A patient with lower lid retraction post
      blepharoplasty was treated with 0.8 SEFFI injections in lower eyelids and malar
      areas, complemented with a bilateral lateral cantopexy. CONCLUSIONS: Autologous
      fat transfer with SEFFI technique is an effective and safe procedure in cases of
      periocular rehabilitation.

PMID- 29040030
TI  - Nivolumab Plus Ipilimumab in Patients With Advanced Melanoma: Updated Survival,
      Response, and Safety Data in a Phase I Dose-Escalation Study.
AB  - Purpose The clinical activity observed in a phase I dose-escalation study of
      concurrent therapy with nivolumab (NIVO) and ipilimumab (IPI) in patients with
      previously treated or untreated advanced melanoma led to subsequent clinical
      development, including randomized trials. Here, we report long-term follow-up
      data from study CA209-004, including 3-year overall survival (OS). Patients and
      Methods Concurrent cohorts 1, 2, 2a, and 3 received escalating doses of NIVO plus
      IPI once every 3 weeks for four doses, followed by NIVO once every 3 weeks for
      four doses, then NIVO plus IPI once every 12 weeks for eight doses. An expansion
      cohort (cohort 8) received concurrent NIVO 1 mg/kg plus IPI 3 mg/kg once every 3
      weeks for four doses, followed by NIVO 3 mg/kg once every 2 weeks, which is the
      dose and schedule used in phase II and III studies and now approved for patients
      with unresectable or metastatic melanoma. Results Among all concurrent cohorts (N
      = 94) at a follow-up of 30.3 to 55.0 months, the 3-year OS rate was 63% and
      median OS had not been reached. Objective response rate by modified WHO criteria
      was 42%, and median duration of response was 22.3 months. Incidence of grade 3
      and 4 treatment-related adverse events was 59%. The most common grade 3 and 4
      treatment-related adverse events were increases in lipase (15%), alanine
      aminotransferase (12%), and aspartate aminotransferase (11%). One treatment
      related death (1.1%) occurred in a patient who had multiorgan failure 70 days
      after the last dose of NIVO plus IPI. Conclusion This is the longest follow-up
      for NIVO plus IPI combination therapy in patients with advanced melanoma. The 3
      year OS rate of 63% is the highest observed for this patient population and
      provides additional evidence for the durable clinical activity of immune
      checkpoint inhibitors in the treatment of advanced melanoma.

PMID- 29040031
TI  - Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti-T
      Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease-Free
      Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic
      Cell Transplantation.
AB  - Purpose Several open-label randomized studies have suggested that in vivo T-cell
      depletion with anti-T-lymphocyte globulin (ATLG; formerly antithymocyte globulin
      Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising
      survival. We report a prospective, double-blind phase III trial to investigate
      the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival.
      Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with
      acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA
      matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned
      one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites.
      Patients received either ATLG or placebo 20 mg/kg per day on days -3, -2, -1 in
      addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study
      end point was moderate-severe cGVHD-free survival. Results Despite a reduction in
      grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v
      33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free
      survival between ATLG and placebo was found (2-year estimate: 48% v 44%,
      respectively; P = .47). Both progression-free survival (PFS) and overall survival
      (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [
      P = .034], respectively). Multivariable analysis confirmed that ATLG was
      associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026)
      and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this
      prospective, randomized, double-blind trial of ATLG in unrelated myeloablative
      HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free
      survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS
      also were lower. Additional analyses are needed to understand the appropriate
      role for ATLG in HCT.

PMID- 29040032
TI  - Interventions and Outcomes in Patients with Infectious Pseudomonas scleritis: A
      10-Year Perspective.
AB  - PURPOSE: To identify interventional factors associated with improved visual
      results and faster time to resolution for patients with Pseudomonas scleritis.
      METHODS: Retrospective study analyzing inciting factors, therapeutic modalities,
      and outcomes of patients with Pseudomonas scleritis. RESULTS: A total of 24
      patients were analyzed; 22 were treated as outpatients. All had resolution of
      infection and 58% (n = 14) maintained >=20/200 vision. Medical therapy included
      topical and oral antibiotics; seven received additional subconjunctival
      injections; two were admitted for IV antibiotics. Patients presenting with
      >=20/200 vision were more likely to maintain this level of vision (n = 8, 80%)
      compared to those presenting with severe vision loss (n = 5, 36%) (p = 0.04). A
      similar proportion of patients who received (n = 8, 61%) and did not receive (n =
      5, 39%) oral steroids achieved 20/200 vision or better once infection resolved, p
      = 1.0. CONCLUSIONS: Pseudomonas scleritis can be successfully managed in the
      outpatient setting. Oral steroids do not appear harmful in the treatment of this
      disease.

PMID- 29040033
TI  - Lower eyelid entropion repair with retractor mobilization and insertion onto the
      anterior surface of the tarsal plate.
AB  - PURPOSE: To evaluate a modified surgical technique for the correction of lower
      eyelid involutional entropion in terms of recurrence rate and relief of symptoms.
      METHOD: A prospective series of 67 consecutive eyelids in 55 patients who
      underwent lower eyelid entropion repair using a modified surgical approach not
      previously published in the literature to the authors' knowledge. The surgical
      technique, via a skin crease incision, involves disinsertion of the lower eyelid
      retractors from the tarsus and conjunctiva and suturing the retractors onto the
      anterior surface of the tarsal plate. Standard excision of redundant lower lid
      skin and orbicularis muscle was also performed as well as lateral canthal tendon
      repair. All procedures were performed by a single surgeon (B. A. O'donnell). This
      study adhered to the principles of the Declaration of Helsinki. RESULTS: There
      were 67 eyelids with a minimum of 12 months follow-up: of these only 1 patient
      (1%) required revision surgery (average follow-up 24 months). Four other eyelids
      had persistent or recurrent irritation (6%) not suggestive of, or secondary to,
      recurrence. Seven eyelids (10%) had undergone previous operative repair with no
      further recurrence following their most recent surgery. CONCLUSION: Disinsertion
      and reattachment of the retractors to the anterior tarsal plate in lower eyelid
      entropion repair is an effective surgical technique to improve lower eyelid
      stability. Although minimum follow-up is 12 months and average follow-up 24
      months, longer follow-up would further evaluate this technique.

PMID- 29040034
TI  - The Use of Language in Diabetes Care and Education.
AB  - Language is powerful and can have a strong impact on perceptions as well as
      behavior. A task force, consisting of representatives from the American
      Association of Diabetes Educators and the American Diabetes Association, convened
      to discuss language in diabetes care and education. The literature supports the
      need for a language movement in diabetes care and education. There are effective
      ways of communicating about diabetes. This article provides recommendations for
      language used by health care professionals and others when discussing diabetes
      through spoken or written words, whether directed to people with diabetes,
      colleagues, or the general public, as well as research questions related to
      language and diabetes.

PMID- 29040035
TI  - Long-Term Efficacy and Safety of Interferon Alpha-2a in the Treatment of Chinese
      Patients with Behcet's Uveitis Not Responding to Conventional Therapy.
AB  - PURPOSE: To investigate the long-term efficacy and safety of interferon alpha-2a
      (IFNalpha-2a) in Chinese patients with Behcet's uveitis (BU) refractory to
      conventional therapy. METHODS: In a prospective observational cohort study, 127
      patients were treated with an initial dosage of 3 million units per day in the
      first three months, followed by gradual tapering of the dose. RESULTS: After 3
      months of treatment, IFNalpha-2a was shown to be effective in 115 cases (91%). At
      the end of the 1-year follow-up, the frequency of ocular relapses decreased to
      1.59 +/- 1.68 per year (ranging 0-6) (p < 0.001), as compared to 5.09 +/- 2.51
      per year (ranging 3-15). Moreover, the frequency of oral ulcer relapses also
      decreased to 2.49 +/- 1.84 per year (ranging 0-6) (p < 0.001), as compared to
      8.20 +/- 3.72 per year (ranging 2-10). Visual improvement or stability was
      observed in 32 patients (59%) in these 54 patients. During a mean follow-up of 11
      months (range 3-33), the mean final VA (logMAR) had progressed from 1.0 logMAR to
      0.8 logMAR in all treated patients. CONCLUSIONS: Long-term low dose of IFNalpha
      2a is useful in treating Chinese BU patients who do not respond adequately to
      conventional therapy.

PMID- 29040036
TI  - Septic thrombosis of cavernous sinus extended to the ipsilateral internal jugular
      vein and transversal sinus with favorable outcome: Clinical and radiological
      features of a Lemierre syndrome.
AB  - An 86-year-old patient was hospitalized for fever and left acute orbital syndrome
      (red eye with moderate visual impairment, chemosis, ophthalmoplegia without
      proptosis, or any fundus involvement). CT scan showed superior ophthalmic vein
      and cavernous sinus enlargement complicating ipsilateral sphenoidal sinusitis.
      Magnetic resonance imaging (MRI) demonstrated the left cavernous sinus thrombosis
      extended to the ipsilateral jugular vein and transversal sinus (Lemierre
      syndrome). Intravenous broad-spectrum antibiotics and curative anticoagulation
      were prescribed. Blood cultures allowed the identification of Streptococcus
      intermedius and Staphylococcus warneri species. Evolution was favorable and the
      patient was discharged 3 weeks after. Antibiotics and anticoagulation were
      carried out for a total duration of 4 and 12 weeks, respectively. Lemierre
      syndrome is a potentially life-threatening emergency rarely encountered; thus,
      ophthalmologists should be cognizant of clinical and radiological features. Broad
      spectrum antibiotics are the mainstay of treatment. Curative anticoagulation may
      be added if no blood coagulation disorder nor bleeding on neuroimaging has been
      identified.

PMID- 29040037
TI  - Influence of Risk Category and Screening Round on the Performance of an MR
      Imaging and Mammography Screening Program in Carriers of the BRCA Mutation and
      Other Women at Increased Risk.
AB  - Purpose To evaluate the real-life performance of a breast cancer screening
      program for women with different categories of increased breast cancer risk with
      multiple follow-up rounds in an academic hospital with a large screening
      population. Materials and Methods Screening examinations (magnetic resonance [MR]
      imaging and mammography) for women at increased breast cancer risk (January 1,
      2003, to January 1, 2014) were evaluated. Risk category, age, recall for workup
      of screening-detected abnormalities, biopsy, and histopathologic diagnosis were
      recorded. Recall rate, biopsy rate, positive predictive value of recall, positive
      predictive value of biopsy, cancer detection rate, sensitivity, and specificity
      were calculated for first and follow-up rounds. Results There were 8818 MR and
      6245 mammographic examinations performed in 2463 women. Documented were 170
      cancers; of these, there were 129 screening-detected cancers, 16 interval
      cancers, and 25 cancers discovered at prophylactic mastectomy. Overall
      sensitivity was 75.9% including the cancers discovered at prophylactic mastectomy
      (95% confidence interval: 69.5%, 82.4%) and 90.0% excluding those cancers (95%
      confidence interval: 83.3%, 93.7%). Sensitivity was lowest for carriers of the
      BRCA1 mutation (66.1% and 81.3% when including and not including cancers in
      prophylactic mastectomy specimens, respectively). Specificity was higher at
      follow-up (96.5%; 95% confidence interval: 96.0%, 96.9%) than in first rounds
      (85.1%; 95% confidence interval: 83.4%, 86.5%) and was high for both MR imaging
      (97.1%; 95% confidence interval: 96.7%, 97.5%) and mammography (98.7%; 95%
      confidence interval: 98.3%, 99.0%). Positive predictive value of recall and
      positive predictive value of biopsy were lowest in women who had only a family
      history of breast cancer. Conclusion Screening performance was dependent on risk
      category. Sensitivity was lowest in carriers of the BRCA1 mutation. The
      specificity of high-risk breast screening improved at follow-up rounds. (c) RSNA,
      2017 Online supplemental material is available for this article.

PMID- 29040038
TI  - Ferumoxytol-enhanced MR Angiography for Vascular Access Mapping before
      Transcatheter Aortic Valve Replacement in Patients with Renal Impairment: A Step
      Toward Patient-specific Care.
AB  - Purpose To assess the technical feasibility of the use of ferumoxytol-enhanced
      (FE) magnetic resonance (MR) angiography for vascular mapping before
      transcatheter aortic valve replacement in patients with renal impairment.
      Materials and Methods This was an institutional review board-approved and HIPAA
      compliant study. FE MR angiography was performed at 3.0 T or 1.5 T. Unenhanced
      computed tomographic (CT) images were used to overlay vascular calcification on
      FE MR angiographic images as composite fused three-dimensional data. Image
      quality of the subclavian and aortoiliofemoral arterial tree and confidence in
      the assessment of calcification were evaluated by using a four-point scale (4 =
      excellent vascular definition or strong confidence). Signal intensity
      nonuniformity as reflected by the heterogeneity index (ratio between the mean
      standard deviation of luminal signal intensity and the mean luminal signal
      intensity), signal-to-noise ratio, and consistency of luminal diameter
      measurements were quantified. Findings at FE MR angiography were compared with
      pelvic angiograms. Results Twenty-six patients underwent FE MR angiography
      without adverse events. A total of 286 named vascular segments were scored. The
      image quality score was 4 for 99% (283 of 286) of the segments (kappa = 0.9).
      There was moderate to strong confidence in the ability to assess vascular
      calcific morphology in all studies with complementary unenhanced CT. The steady
      state luminal heterogeneity index was low, and signal-to-noise ratio was high.
      Interobserver luminal measurements were reliable (intraclass correlation
      coefficient, 0.98; 95% confidence interval: 0.98, 0.99). FE MR angiographic
      findings were consistent with correlative pelvic angiograms in all 16 patients
      for whom the latter were available. Conclusion In patients with renal impairment
      undergoing transcatheter aortic valve replacement, FE MR angiography is
      technically feasible and offers reliable vascular mapping without exposure to
      iodine- or gadolinium-based contrast agents. Thus, the total cumulative dose of
      iodine-based contrast material is minimized and the risk of acute nephropathy is
      reduced. (c) RSNA, 2017 Online supplemental material is available for this
      article.

PMID- 29040039
TI  - Breast Cancer Risk Associations with Digital Mammographic Density by Pixel
      Brightness Threshold and Mammographic System.
AB  - Purpose To compare three mammographic density measures defined by different pixel
      intensity thresholds as predictors of breast cancer risk for two different
      digital mammographic systems. Materials and Methods The Korean Breast Cancer
      Study included 398 women with invasive breast cancer and 737 control participants
      matched for age at mammography (+/-1 year), examination date, mammographic
      system, and menopausal status. Mammographic density was measured by using the
      automated Laboratory for Individualized Breast Radiodensity Assessment (LIBRA)
      software and the semiautomated Cumulus software at the conventional threshold
      (Cumulus) and at increasingly higher thresholds (Altocumulus and Cirrocumulus,
      respectively). Measures were Box-Cox-transformed and adjusted for age, body mass
      index, and menopausal status. Conditional logistic regression was used to
      estimate risk associations. For calculation of measures of predictive value, the
      change in odds per standard deviation (OPERA) and the area under the receiver
      operating characteristic curve (AUC) were used. Results For dense area, with use
      of the direct conversion system the OPERAs were 1.72 (95% confidence interval
      [CI]: 1.38, 2.15) for LIBRA, 1.58 (95% CI: 1.27, 1.97) for Cumulus, 2.04 (95% CI:
      1.60, 2.59) for Altocumulus, and 3.48 (95% CI: 2.45, 4.47) for Cirrocumulus (P <
      .001). The corresponding AUCs were 0.70, 0.69, 0.76, and 0.89, respectively. With
      use of the indirect conversion system, the corresponding OPERAs were 1.50 (95%
      CI: 1.28, 1.76), 1.36 (95% CI: 1.16, 1.59), 1.40 (95% CI: 1.19, 1.64), and 1.47
      (95% CI: 1.25, 1.73) (P < .001) and the AUCs were 0.64, 0.60, 0.61, and 0.63,
      respectively. Conclusion It is possible that mammographic density defined by
      higher pixel thresholds could capture more risk-predicting information with use
      of a direct conversion mammographic system; the mammographically bright, rather
      than white, regions are etiologically important. (c) RSNA, 2017.

PMID- 29040040
TI  - Prevalence of Carotid Web in Patients with Acute Intracranial Stroke Due to
      Intracranial Large Vessel Occlusion.
AB  - Purpose To investigate the prevalence of symptomatic carotid web in patients with
      acute ischemic stroke due to intracranial large vessel occlusion, to determine
      the clinical and imaging profile of patients with carotid web as well as their
      association with ischemic stroke, and to determine the interobserver agreement in
      the assessment of carotid webs. Materials and Methods All patients (n = 500) of
      the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute
      Ischemic Stroke in the Netherlands (MR CLEAN) in whom the carotid bifurcation
      could be assessed (n = 443) were included. The presence of a carotid web at the
      carotid bifurcations was evaluated at computed tomographic (CT) angiography.
      Demographics, clinical characteristics, and imaging baseline characteristics were
      presented by descriptive statistics for patients with an identified carotid web.
      Interobserver agreement in the detection of carotid webs was examined by using
      kappa statistics. Results Eleven (2.5%) carotid webs were found at the
      symptomatic side and two (0.5%) carotid webs were found at the asymptomatic side.
      Ten (91%) patients with a symptomatic carotid web were female. Nine patients with
      a symptomatic carotid web did not have major risk factors or other causes for
      ischemic stroke (82%). Fair to good interobserver agreement (kappa, 0.72) was
      observed for diagnosing carotid webs at CT angiography. Conclusion Carotid webs
      at the symptomatic carotid bifurcation were observed in 2.5% of the patients with
      acute ischemic stroke due to large vessel occlusion and were mostly diagnosed in
      female patients with a fair to good interobserver agreement. (c) RSNA, 2017
      Clinical trial registration nos. NTR1804 and ISRCTN10888758 Online supplemental
      material is available for this article.

PMID- 29040041
TI  - Coordinating Care for Students With Chronic Conditions: CLUE #1.
AB  - Care coordination is an important part of school nurses' responsibilities, but
      coordinating that care for students in schools with chronic conditions is more
      complex than what we learned in nursing school. This article is the second in a
      series of articles for NASN School Nurse that will delve into how to apply
      evidence-based practice (EBP) to school nursing. The article focuses on the first
      step of EBP: asking the question. As the series progresses, we encourage you to
      apply the steps to a situation in your setting or even use the series to increase
      discussions at nursing staff meetings so all can benefit.

PMID- 29040042
TI  - Mental Health First Aid: A Useful Tool for School Nurses.
AB  - School nurses address mental health issues of youth on a daily basis. These
      mental health issues include substance abuse, anxiety, depression, and even
      suicidal ideation. Mental health first aid is a process that seeks to help
      medical professionals and laypeople recognize and address someone that is having
      a mental health or substance abuse crisis. This article will describe an
      experience with a student having suicidal ideations and how the mental health
      action plan was used.

PMID- 29040043
TI  - Depression Screening in the School Setting: Identification of the Depressed
      Adolescent.
AB  - Adolescent depression is a silent epidemic in this country. Untreated depression
      has detrimental effects on physical health, psychosocial well-being, and academic
      productivity. It is important for school nurses to be able to recognize
      depression and refer students promptly for treatment. This article and its
      associated learning module will provide school nurses with updated information on
      adolescent depression, discuss barriers in depression screening, use of the PHQ-9
      (Patient Health Questionaire-9 Item) as an evidence-based depression screening
      tool in the educational setting, and the important role of school nurses in
      depression screening. It is anticipated that by increasing awareness and
      knowledge about adolescent depression and providing training in the use of an
      evidence-based screening tool, school nurses will have greater confidence in
      identifying and referring students in need. (A free online depression screening
      education module developed by the lead author is available at
      https://sites.google.com/view/depressionscreeningtraining .).

PMID- 29040044
TI  - Step Up & Be Counted! Strategies for Data Collection.
AB  - Step Up & Be Counted! (Step Up!) is an innovative project to collect nationally
      standardized data from the daily documentation of school nurses throughout the
      United States. Step Up! provides the standardization needed to promote an "apples
      to apples" analysis of school health resources, interventions, and outcomes
      across the United States. While some states have collected data for decades and
      have an effective infrastructure in place, other states are new to data
      collection and are creating processes to support data collection. Designated
      State Data Champions have volunteered to collect aggregated de-identified data
      from school districts throughout their state. The following is a discussion of
      some of the data collection innovations shared by Designated State Data Champions
      at the 2017 NASN Annual Conference.

PMID- 29040045
TI  - Being a Grateful Leader.

PMID- 29040048
TI  - Pulmonary Vascular Research Institute World Congress 2017 Scientific Abstracts.

PMID- 29040047
TI  - Ultra-Widefield Fluorescein Angiography in Intermediate Uveitis.
AB  - PURPOSE: To examine associations between pattern of vascular leakage on ultrawide
      field fluorescein angiography (UWFFA) and visual acuity, cystoid macular edema
      (CME), and inflammatory activity in intermediate uveitis. METHODS: Single center
      cross-sectional, retrospective review of medical records, spectral domain optical
      coherence tomography (SD-OCT) and angiographic images of intermediate uveitis
      patients who underwent UWFFA over a 12-month period. RESULTS: Forty-one eyes from
      24 patients were included. Twelve eyes (29%) exhibited peripheral leakage, 26
      eyes (64%) had diffuse leakage and three eyes (7%) had no leakage. Diffuse
      leakage was associated with 0.2 logMAR worse visual acuity than peripheral
      leakage (p = 0.02). There was no statistically significant difference in the odds
      of having CME when diffuse leakage was compared to peripheral leakage.
      CONCLUSION: UWFFA identifies retinal vascular pathology in intermediate uveitis
      not present on clinical examination. Diffuse retinal vascular leakage was
      associated with worse visual acuity when compared to peripheral and no leakage
      patterns.

PMID- 29040049
TI  - Recent trends in common chemical feed and food contaminants in Israel.
AB  - In February 2014 a new law was approved by the Israeli parliament, namely the
      Control of Animal Feed Law. The law intends to regulate the production and
      marketing of animal feed. In preparation for the law's implementation in 2017, we
      have assessed the current feed and food safety challenges in Israel in recent
      years in association with the presence of common undesirable contaminants in
      various common feed and food commodities. Tight collaboration between regulatory
      authorities and feed/food industry, enhanced feed and food quality monitoring,
      transparency of survey results and readily accessible and reliable information
      for the public about health hazards of chemical contaminants, will guarantee the
      safety and quality of food and feed.

PMID- 29040050
TI  - Latent Autoimmune Diabetes in Adults in North Indian Region: Assessment of beta
      Cell Function, Metabolic and Immunological Features.
AB  - BACKGROUND: We undertook a study to assess beta-cell function, metabolic and
      immunological features of patients with latent autoimmune diabetes in adults
      (LADA) and investigate heterogeneity within LADA based on low and high glutamic
      acid decarboxylase autoantibodies (GADA) titers. METHODS: A total of 139 patients
      with adult-onset diabetes were examined cross-sectionally in the National capital
      region of Northern India. Medical history of all subjects was reviewed with the
      aim of collecting clinical data. Glucose, glycosylated hemoglobin, lipid profile,
      creatinine, C-peptide, and GADA were measured in 10-12 hrs fasting blood sample.
      RESULTS: Assessment of metabolic features revealed lower mean systolic blood
      pressure in subjects with LADA than in those with type 2 diabetes (DM2). Mean
      triglyceride levels were lower in LADA subjects compared to DM2 subjects.
      Compared to DM2 subjects, prevalence of metabolic syndrome (MS) was also lower in
      LADA subjects. Compared to GADA-low, all GADA-high patients were male, had lower
      waist circumference, fasting C-peptide (FCP), and prevalence of MS. Compared to
      DM2 patients, GADA-high patients were younger, had lower age at onset, body mass
      index, waist circumference, systolic blood pressure, triglycerides, FCP, and
      prevalence of MS. The rate of patients on insulin was higher in GADA-high
      compared to DM2. There were no significant differences between characteristics of
      DM2 and GADA-low patients. CONCLUSIONS: Our results indicate that LADA patients
      have distinct metabolic features with lower residual beta-cell function than DM2
      patients. GADA titer is important parameter in defining the severity of the
      disease as patients with high GADA titer tend to have significant beta-cell
      impairment.

PMID- 29040051
TI  - Two Novel CAPN5 Variants Associated with Mild and Severe Autosomal Dominant
      Neovascular Inflammatory Vitreoretinopathy Phenotypes.
AB  - PURPOSE: We report two new CAPN5 mutations associated with a phenotype of
      Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy. METHODS: We
      performed next generation sequencing in two patients with ADNIV phenotype; the
      variants identified were explored further. RESULTS: Patient 1 was heterozygous
      for CAPN5 c.799G>A, p.(Gly267Ser). Patient 2 was heterozygous for CAPN5
      c.1126G>A, p.(Gly376Ser). Both amino acids are highly conserved across species.
      Patient 1 had a severe phenotype and his mutation lies within the protein's
      catalytic domain. Patient 2 had a mild phenotype and her mutation is the first
      ADNIV-causing mutation to be described in the regulatory domain of Calpain-5.
      CONCLUSIONS: Our findings potentially add two new ADNIV-causing CAPN5 mutations
      to the three previously described. We recommend CAPN5 genetic testing in all
      patients with a possible ADNIV phenotype, to develop our understanding of Calpain
      5; a protein which could potentially provide therapeutically accessible targets
      for the treatment of many leading causes of blindness.

PMID- 29040052
TI  - Partial or entire: Distinct responses of two types of chloroplast autophagy.
AB  - Autophagy carries out intracellular degradation of cytoplasmic components, which
      is important for the removal of dysfunctional organelles and for efficient
      nutrient recycling in eukaryotic cells. Most proteins in plant green tissues are
      found in chloroplasts, mainly as photosynthetic proteins that constantly
      accumulate damage caused by sunlight. Our recent study investigated the
      involvement of autophagy in the turnover of damaged chloroplasts and found that
      entire photodamaged chloroplasts are transported into the vacuole for degradation
      via an autophagy process termed chlorophagy. Our previous studies also
      established that autophagy can also degrade chloroplast components piecemeal:
      chloroplast stroma is transported for degradation via autophagy vesicles termed
      Rubisco-containing bodies (RCB). During sugar starvation-induced senescence in
      darkened leaves, the RCB pathway is preferentially active. By contrast, we
      observed active chlorophagy without prior induction of RCB production in
      photodamaged leaves. These distinct responses between the RCB pathway and
      chlorophagy support the notion that the induction of the partial-type and entire
      organelle-type chloroplast autophagy are differentially regulated by individual
      upstream molecules. This finding further suggests that the two types of autophagy
      are coordinated to achieve the controlled chloroplast turnover in response to
      specific conditions.

PMID- 29040053
TI  - Periostin as a Biomarker for Nasal Polyps in Chronic Rhinosinusitis.
AB  - Objective Periostin is an extracellular matrix protein that is elevated in the
      sinonasal tissues of patients with chronic rhinosinusitis (CRS). The purpose of
      this study was to determine whether serum periostin could serve as a molecular
      biomarker of nasal polyp burden in sinonasal disease. Study Design Prospective
      cohort study. Setting Academic medical center. Subjects and Methods Serum
      periostin levels were measured by ELISA on blood samples collected from patients
      undergoing sinus surgery for CRS (n = 71), further stratified by phenotype as
      defined by nasal polyps and asthma. Results were compared with assays performed
      on control subjects (n = 62). Results Mean serum periostin levels were markedly
      elevated in patients with CRS versus controls (66.1 ng/mL [95% CI, 51.6-80.6] vs
      38.7 ng/mL [95% CI, 34.4-42.9], respectively, P = .004). In addition, mean
      periostin levels were significantly higher in CRS patients with nasal polyps as
      compared with those without polyps (94.8 ng/mL [95% CI, 67.3-122.4] vs 41.1 ng/mL
      [95% CI, 35.2-47.0], respectively, P < .001). Periostin levels did not correlate
      with sex ( P = .473), smoking history ( P = .748), aspirin-exacerbated
      respiratory disease status ( P = .136), oral steroid use within 1 month of
      surgery ( P = .281), use of topical steroid nasal spray ( P = .864), or number of
      prior sinus operations ( P = .973). Conclusion Serum periostin appears to be a
      novel molecular biomarker for the presence of nasal polyps and may serve as an
      indicator of CRS endotypes.

PMID- 29040054
TI  - Pediatric NUT-midline carcinoma: Therapeutic success employing a sarcoma based
      multimodal approach.
AB  - A subset of poorly differentiated squamous cell carcinomas, NUT midline
      carcinomas (NMC) are characterized by a translocation t(15;19)(q13;p13) [ 1 ].
      The prognosis is generally dismal [ 2 ] and therapeutic success has been limited
      to exceptional cases [ 3 ]. We present two cases of pediatric NMC from two
      different institutions treated according to a multimodal sarcoma approach
      involving surgery, chemotherapy, and focal radiotherapy. One patient has remained
      in complete continuous remission for over 6 years, while the other is in CR in
      early follow-up off therapy. Our proposed multimodal strategy apparently meets
      the aggressive biologic nature of NMC and should be considered for further
      evaluation in this context potentially in the setting of a clinical trial.

PMID- 29040055
TI  - The Empirical Case for Acquiescing to Intuition.
AB  - Will people follow their intuition even when they explicitly recognize that it is
      irrational to do so? Dual-process models of judgment and decision making are
      often based on the assumption that the correction of errors necessarily follows
      the detection of errors. But this assumption does not always hold. People can
      explicitly recognize that their intuitive judgment is wrong but nevertheless
      maintain it, a phenomenon known as acquiescence. Although anecdotes and
      experimental studies suggest that acquiescence occurs, the empirical case for
      acquiescence has not been definitively established. In four studies-using the
      ratio-bias paradigm, a lottery exchange game, blackjack, and a football coaching
      decision-we tested acquiescence using recently established criteria. We provide
      clear empirical support for acquiescence: People can have a faulty intuitive
      belief about the world (Criterion 1), acknowledge the belief is irrational
      (Criterion 2), but follow their intuition nonetheless (Criterion 3)-even at a
      cost.

PMID- 29040056
TI  - An Integrated Control Strategy Takes Clonorchis sinensis Under Control in an
      Endemic Area in South China.
AB  - Clonorchis sinensis is an important foodborne zoonosis worldwide and prevalent in
      China for more than 2000 years. According to the experience of controlling
      Schistosoma japonica, China started to establish the integrated control strategy
      for C. sinensis in endemic areas. Lou village, the largest village in Shenzhen
      city in South China was taken as a pilot site. This longitudinal study assessed
      the infection status of C. sinensis among people and intermediate hosts from 2006
      to 2014 in Lou village. After a continuous intervention with the integrated
      control strategy, the prevalence of C. sinensis decreased significantly to 2.01%
      in 2014. The infection intensity also reduced significantly with eggs per gram
      varying from 45.6 +/- 3.4 in 2010 to 21.7 +/- 1.6 in 2012. There is also a
      statistically significant decrease of the prevalence of C. sinensis metacercariae
      in fish hosts from 16.51% in 2008 before the intervention to 5.33% in 2014. All
      the old-styled toilets were replaced by sanitary ones with a harmless processing
      design in 2014. No viable parasite eggs were detected in stool samples from the
      reconstructed toilets. Health education played an important role in changing the
      eating habits among the local residents, with a significant decrease in the
      prevalence of eating raw fish from 91.99% in 2008 to 59.87% in 2014. The
      evaluation suggested that the integrated strategy we have performed in Lou
      village is effective in controlling the C. sinensis infection and maintaining the
      infection rate at a lower level, which can be promoted in other endemic areas.

PMID- 29040057
TI  - Validity of algorithm for estimating left sided filling pressures on
      echocardiography in a population referred for pulmonary arterial hypertension.
AB  - The determination of LV filling pressure is integral to the diagnosis of
      pulmonary arterial hypertension (PAH). The American Society of Echocardiography
      (ASE) has devised algorithms for their estimation. We aimed to test these
      algorithms in a population referred for suspected PAH. In our retrospective
      study, we evaluated the accuracy of the ASE Algorithms compared to right heart
      catheterization done within three months, in patients seen during 2006-2014. All
      echocardiograms were classified as showing normal, elevated or indeterminate
      filling pressures. Those with indeterminate pressures were excluded. We evaluated
      the diagnostic properties of this algorithm to predict a pulmonary artery wedge
      pressure (PAWP) and left ventricular end diastolic pressure (LVEDP) >15 mmHg. A
      total of 94 patients were included. The ASE algorithms yielded indeterminate
      results in 50 (53.2%) patients. This occurred more commonly in older patients and
      patients with cardiovascular comorbidities. The algorithm had a high sensitivity
      for predicting an elevated PAWP at 89.5% (95% confidence interval [CI] = 66.9
      98.7) and an elevated LVEDP at 100% (95% CI = 76.8-100). The algorithm had a
      negative predictive value of 81.8% and 100% for predicting an elevated PAWP (95%
      CI = 52.4-94.8) and LVEDP, respectively, but a poor positive predictive value.
      The ASE algorithm for predicting LV filling pressures often cannot be applied in
      populations with suspected PAH. When they are interpretable, they have a high
      negative predictive value for elevated PAWP and LVEDP. We recommend caution when
      using these algorithms in populations with suspected PAH.

PMID- 29040058
TI  - Recommendations for Laboratory Containment and Management of Gene Drive Systems
      in Arthropods.
AB  - Versatile molecular tools for creating driving transgenes and other invasive
      genetic factors present regulatory, ethical, and environmental challenges that
      should be addressed to ensure their safe use. In this article, we discuss driving
      transgenes and invasive genetic factors that can potentially spread after their
      introduction into a small proportion of individuals in a population. The
      potential of invasive genetic factors to increase their number in natural
      populations presents challenges that require additional safety measures not
      provided by previous recommendations regarding accidental release of arthropods.
      In addition to providing physical containment, invasive genetic factors require
      greater attention to strain management, including their distribution and identity
      confirmation. In this study, we focus on insects containing such factors with
      recommendations for investigators who are creating them, institutional biosafety
      committees charged with ensuring safety, funding agencies providing support,
      those managing insectaries handling these materials who are responsible for
      containment, and other persons who will be receiving insects-transgenic or not
      from these facilities. We give specific examples of efforts to modify mosquitoes
      for mosquito-borne disease control, but similar considerations are relevant to
      other arthropods that are important to human health, the environment, and
      agriculture.

PMID- 29040060
TI  - Structure and function of the human parvulins Pin1 and Par14/17.
AB  - Parvulins belong to the family of peptidyl-prolyl cis/trans isomerases (PPIases)
      assisting in protein folding and in regulating the function of a broad variety of
      proteins in all branches of life. The human representatives Pin1 and Par14/17 are
      directly involved in processes influencing cellular maintenance and cell fate
      decisions such as cell-cycle progression, metabolic pathways and ribosome
      biogenesis. This review on human parvulins summarizes the current knowledge of
      these enzymes and intends to oppose the well-studied Pin1 to its less well
      examined homolog human Par14/17 with respect to structure, catalytic and cellular
      function.

PMID- 29040059
TI  - Circadian rhythm genes mediate fenvalerate-induced inhibition of testosterone
      synthesis in mouse Leydig cells.
AB  - Fenvalerate (Fen), a widely used pesticide, is known to impair male reproductive
      functions by mechanisms that remain to be elucidated. Recent studies indicated
      that circadian clock genes may play an important role in successful male
      reproduction. The aim of this study was to determine the effects of Fen on
      circadian clock genes involved in the biosynthesis of testosterone using TM3
      cells derived from mouse Leydig cells. Data demonstrated that the circadian
      rhythm of testosterone synthesis in TM3 cells was disturbed following Fen
      treatment as evidenced by changes in the circadian rhythmicity of core clock
      genes (Bmal1, Rev-erbalpha, Roralpha). Further, the observed altered rhythms were
      accompanied by increased intracellular Ca2+ levels and modified steroidogenic
      acute regulatory (StAR) mRNA expression. Thus, data suggested that Fen inhibits
      testosterone synthesis via pathways involving intracellular Ca2+ and clock genes
      (Bmal1, Rev-Erbalpha, Roralpha) as well as StAR mRNA expression in TM3 cells.

PMID- 29040061
TI  - Validation of a novel biomechanical test bench for the knee joint with six
      degrees of freedom.
AB  - A novel biomechanical test bench has been developed for in-vitro evaluation of
      the knee joint. The test bench allows the kinematics of the knee joint to be
      studied in all six degrees of freedom. Flexion-extension knee movements are
      induced by quadriceps and hamstring muscle forces simulated by five pneumatic
      cylinders. The kinematics of the knee and the actively applied muscle forces are
      measured simultaneously. The aim of this study was to validate the sensitivity
      and reproducibility of this novel test bench. Four fresh frozen human knees were
      tested three times, each with seven flexion-extension cycles between 5 degrees 
      and 60 degrees . After the native knees had been tested, the posterior cruciate
      ligament and then the lateral collateral ligament were dissected. The injured
      knees were tested in identical conditions [3*(7*5 degrees -60 degrees )] in order
      to evaluate whether the test bench is capable of detecting differences in knee
      kinematics between a native state and an injured one. With regard to
      reproducibility, the novel test bench showed almost perfect agreement for each
      specimen and for all states and flexion angles. In comparison with the native
      knees, the injured knees showed significant differences in knee kinematics. This
      validated novel test bench will make it possible to investigate various knee
      pathologies, as well as current and newly developed treatment options.

PMID- 29040062
TI  - Influence of delayed separation of plasma from whole blood on Cu, I, Mn, Se, and
      Zn plasma concentrations.

PMID- 29040063
TI  - Validation of the Six Sigma Z-score for the quality assessment of clinical
      laboratory timeliness.
AB  - BACKGROUND: The International Federation of Clinical Chemistry and Laboratory
      Medicine has introduced in recent times the turnaround time (TAT) as mandatory
      quality indicator for the postanalytical phase. Classic TAT indicators, namely,
      average, median, 90th percentile and proportion of acceptable test (PAT), are in
      use since almost 40 years and to date represent the mainstay for gauging the
      laboratory timeliness. In this study, we investigated the performance of the Six
      Sigma Z-score, which was previously introduced as a device for the quantitative
      assessment of timeliness. METHODS: A numerical simulation was obtained modeling
      the actual TAT data set using the log-logistic probability density function. Five
      thousand replicates for each size of the artificial TAT random sample (n=20, 50,
      250 and 1000) were generated, and different laboratory conditions were simulated
      manipulating the PDF in order to generate more or less variable data. The Z-score
      and the classic TAT indicators were assessed for precision (%CV), robustness
      toward right-tailing (precision at different sample variability), sensitivity and
      specificity. RESULTS: Z-score showed sensitivity and specificity comparable to
      PAT (~80% with n>=250), but superior precision that ranged within 20% by
      moderately small sized samples (n>=50); furthermore, Z-score was less affected by
      the value of the cutoff used for setting the acceptable TAT, as well as by the
      sample variability that reflected into the magnitude of right-tailing.
      CONCLUSIONS: The Z-score was a valid indicator of laboratory timeliness and a
      suitable device to improve as well as to maintain the achieved quality level.

PMID- 29040064
TI  - Strong impact on plasma protein profiles by precentrifugation delay but not by
      repeated freeze-thaw cycles, as analyzed using multiplex proximity extension
      assays.
AB  - Background A number of factors regarding blood collection, handling and storage
      may affect sample quality. The purpose of this study was to assess the impact on
      plasma protein profiles by delayed centrifugation and plasma separation and
      multiple freeze-thaw cycles. Methods Blood samples drawn from 16 healthy
      individuals were collected into ethylenediaminetetraacetic acid tubes and kept
      either at 4  degrees C or 22  degrees C for 1-36 h prior to centrifugation.
      Plasma samples prepared 1 h after venipuncture were also subjected to two to
      eight cycles of freezing at -80  degrees C and thawing at 22  degrees C.
      Multiplex proximity extension assay, an antibody-based protein assay, was used to
      investigate the influence on plasma proteins. Results Up to 36 h delay before
      blood centrifugation resulted in significant increases of 16 and 40 out of 139
      detectable proteins in samples kept at 4  degrees C or 22  degrees C,
      respectively. Some increases became noticeable after 8 h delay at 4  degrees C
      but already after 1 h at 22  degrees C. For samples stored at 4  degrees C,
      epidermal growth factor (EGF), NF-kappa-B essential modulator, SRC, interleukin
      16 and CD6 increased the most, whereas the five most significantly increased
      proteins after storage at 22  degrees C were CD40 antigen ligand (CD40-L), EGF,
      platelet-derived growth factor subunit B, C-X-C motif chemokine ligand 5 and
      matrix metallopeptidase 1 (MMP1). Only matrix metallopeptidase 7 (MMP7) decreased
      significantly over time and only after storage at 22  degrees C. No protein
      levels were found to be significantly affected by up to eight freeze-thaw cycles.
      Conclusions Plasma should be prepared from blood after a limited
      precentrifugation delay at a refrigerated temperature. By contrast, the influence
      by several freeze-thaw cycles on detectable protein levels in plasma was
      negligible.

PMID- 29040065
TI  - Tumor microenvironment and systemic disease: a dual target in medical oncology
      (also in the case of biomarkers).

PMID- 29040066
TI  - Evaluation of oral multi-herbal preparation of Dashmoolarishta on mice model of
      osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) is a chronic progressive disease commonly
      affecting the hip and knee joints. Although synthetic drugs are available and
      afford symptomatic relief, their side effects pose limitations to their
      continuous use. So, this research was focused on extracting drugs from indigenous
      medicinal plants that could have a beneficial effect on osteoarthritis.
      Dashmoolarishta is one such preparation whose effects have never been studied in
      comparison with recent drugs like hyaluronic acid (HA), hence this particular
      study was undertaken. The aim of this study was to evaluate the effects of
      Dashmoolarishta compared with HA on joint pathology and pain behavior in
      monosodiumiodoacetate (MIA)-induced OA in experimental mice. METHODS: The study
      was initiated after obtaining permission from the Animal Ethics Committee. This
      study was based on the MIA model of osteoarthritis, with mice being divided into
      five groups viz.: disease control (DC), Dasahmoolarishta high dose (HD) and low
      dose (LD), sham control (SC) and HA. The OA of the knee joint was induced in
      these mice using monosodiumiodoacetate. Seven days after induction, animals were
      subjected to weekly behavioral tests, daily oral Dashmoolarishta, and biweekly HA
      administration from weeks 2-4. At the end of the 4th week, histopathological
      examination of the knee joints was done. RESULTS: DC showed significant
      osteoarthritic changes. At week 4, the behavioral tests and histopathology
      results of all groups were found to be significant. A significant difference
      (p<0.05) was found between DC vs. SC, HA, HD, LD for open field test, Rota rod
      test, knee joint diameter, and Cat walk test. Dashmoolarishta HD and LD showed
      significant improvement in pain, as assessed by behavioral tests (p<0.05) and
      pathology, as assessed by knee joint histopathology (p<0.05). CONCLUSIONS: Oral
      Dashmoolarishta showed reduction in pain and disease activity in MIA-induced
      osteoarthritis in mice model.

PMID- 29040067
TI  - Early-onset severe obesity due to complete deletion of the leptin gene in a boy.
AB  - BACKGROUND: Monogenic obesity results from single gene mutations. Extreme obesity
      starting at an early age, especially in infancy, which is associated with
      endocrinopathy and metabolic disturbances is key to the diagnosis of monogenic
      obesity. CASE PRESENTATION: A 6-month-old boy was admitted to our clinic with
      severe obesity and food craving. He was born with a birth weight of 3400 g to
      first-cousin parents. He started to gain weight at an abnormal rate at the age of
      2 months. He had hyperinsulinemia, dyslipidemia and grade 2 hepatosteatosis. He
      had a 7-year-old, healthy brother with a normal body weight. Because of severe
      early-onset obesity and abnormal food addiction, his leptin level was measured
      and found to be 0.55 ng/mL (normal range for his age and sex is 0.7-21 ng/mL). A
      LEP gene mutation was screened for and a gross leptin gene deletion was detected.
      To date, no report on a gross deletion of the LEP gene has been published in the
      literature. CONCLUSIONS: To the best of our knowledge, a gross deletion of the
      LEP gene has not been reported so far in the literature. Here we report a unique
      case with congenital leptin deficiency. Thus, clinicians should search for
      monogenic obesity in patients with early-onset severe obesity and endocrinopathy.
      Measuring the leptin level could aid clinicians to identify children with
      monogenic obesity.

PMID- 29040068
TI  - Secular trends in height, weight and body mass index of primary school children
      in Turkey between 1993 and 2016.
AB  - BACKGROUND: The aim of the study was to analyze the secular trends in height,
      weight and body mass index (BMI) of children in a Turkish primary school in a 23
      year time interval. METHODS: The height, weight and BMI of 1099 children between
      7 and 15 years old were measured. Data were compared to those of children of the
      same ages from previous measurements carried out in 1993 (867 children) and in
      2003 (1214 children) in the same school. The changes in weight, height and BMI
      were determined and analyzed statistically. RESULTS: Weight increments between
      7.7 and 16.2 kg/23 years and height increments between 1.1 and 8.3 cm/23 years
      were observed in boys. For girls, weight increments between 6.5 and 13.4 kg/23
      years and height increments between 1.3 and 7.2 cm/23 years were indicated.
      Usually, there were significant height increments between 1993 and 2016 in both
      genders. However, there were no significant differences in height between 2003
      and 2016 for all age groups. Furthermore, there were significant differences in
      BMI measurements in all age and gender groups between 1993 and 2016. CONCLUSIONS:
      The secular ascending trend in height seems to stop between 2003 and 2016;
      however, increments in weight and mean BMI tend to continue in Turkish primary
      school children and adolescents.

PMID- 29040069
TI  - Effects of 1-year growth hormone replacement therapy on thyroid volume and
      function of the children and adolescents with idiopathic growth hormone
      deficiency.
AB  - BACKGROUND: There are different opinions about the effects of growth hormone
      replacement therapy (GHRT) on thyroid function and volume. This study aimed to
      assess the effects of GHRT on thyroid volume and function in the children and
      adolescents with growth hormone (GH) deficiency. METHODS: A total of 29 patients
      diagnosed with GH deficiency were enrolled in the study. The control group
      consisted of 29 cases matched for age, gender and pubertal period with the
      patients. Thyroid function tests and insulin-like growth factor levels were
      measured, simultaneously thyroid volumes were assessed by ultrasonography at the
      initiation period and at the end of GHRT. RESULTS: Thyroid volumes of the patient
      group was -0.55+/-1.1 standard deviations (SDs) initially; whereas at the end of
      1 year it was found to be -0.29+/-1.29 SDs and both SDs of thyroid volumes did
      not differ significantly. The SDs of thyroid volume of the control group was 
      0.85+/-1.03 SDs initially and -0.72+/-0.85 SDs at the end of 1 year; and they did
      not differ significantly. On the other hand, after GHRT of 1 year, thyroid
      stimulating hormone (TSH) and free thyroxine (T4) levels decreased. CONCLUSIONS:
      It was observed that SDs of thyroid gland volumes did not change in GH deficient
      children and adolescents after GHRT.

PMID- 29040070
TI  - Modulating the electronic and optical properties of monolayer arsenene phases by
      organic molecular doping.
AB  - Recently, arsenene monolayer structure of the arsenic with two phases has
      displayed semiconducting behavior. We have systematically investigated the
      electronic and optical properties of single-layer arsenene with two types of
      functionalized organic molecules; an electrophilic molecule
      [tetracyanoquinodimethane (TCNQ)] and a nucleophilic molecule [tetrathiafulvalene
      (TTF)], as an electron acceptor and electron donor, respectively. The interfacial
      charge transfer between the arsenene monolayer and TCNQ/TTF molecules extensively
      reduces the band gap of arsenene and accordingly resulted in a p- or n-type
      semiconducting behavior, respectively. We have also performed the interfacial
      charge transfer from organic molecules to monolayer arsenene and vice versa. The
      interfacial surface molecular modification has established an efficient way to
      develop the light harvesting of arsenene in different polarization directions.
      Our theoretical investigation suggests that such n- and p-type arsenene
      semiconductors would broaden the applications in the field of nanoelectronic and
      optoelectronic devices such as photodiodes and it is also useful for constructing
      functional electronic systems.

PMID- 29040071
TI  - Prevalence and direct costs of emergency department visits and hospitalizations
      for selected diseases that can be transmitted by water, United States.
AB  - National emergency department (ED) visit prevalence and costs for selected
      diseases that can be transmitted by water were estimated using large healthcare
      databases (acute otitis externa, campylobacteriosis, cryptosporidiosis,
      Escherichia coli infection, free-living ameba infection, giardiasis, hepatitis A
      virus (HAV) infection, Legionnaires' disease, nontuberculous mycobacterial (NTM)
      infection, Pseudomonas-related pneumonia or septicemia, salmonellosis,
      shigellosis, and vibriosis or cholera). An estimated 477,000 annual ED visits
      (95% CI: 459,000-494,000) were documented, with 21% (n = 101,000, 95% CI: 97,000
      105,000) resulting in immediate hospital admission. The remaining 376,000 annual
      treat-and-release ED visits (95% CI: 361,000-390,000) resulted in $194 million in
      annual direct costs. Most treat-and-release ED visits (97%) and costs ($178
      million/year) were associated with acute otitis externa. HAV ($5.5 million), NTM
      ($2.3 million), and salmonellosis ($2.2 million) were associated with next
      highest total costs. Cryptosporidiosis ($2,035), campylobacteriosis ($1,783), and
      NTM ($1,709) had the highest mean costs per treat-and-release ED visit. Overall,
      the annual hospitalization and treat-and-release ED visit costs associated with
      the selected diseases totaled $3.8 billion. As most of these diseases are not
      solely transmitted by water, an attribution process is needed as a next step to
      determine the proportion of these visits and costs attributable to waterborne
      transmission.

PMID- 29040072
TI  - Enterococci populations of a metropolitan river after an extreme flood event:
      prevalence, persistence and virulence determinants.
AB  - We investigated the prevalence, persistence and virulence determinants of
      enterococci populations in water samples collected over three rounds following an
      extreme flood event in a metropolitan river. Enterococci (n = 482) were typed
      using the high resolution biochemical fingerprinting method (PhP typing) and
      grouped into common (C) or single (S) biochemical phenotypes (BPTs). In all, 23 C
      BPTs (72.6% of isolates) were found across the sites. A representative isolate of
      each C-BPT was identified to the species level and tested for the presence of
      seven virulence genes (VGs), biofilm formation and resistance to 14 antibiotics.
      The enterococci concentrations in samples collected during the first two rounds
      were above national recreational water guidelines. By round three, enterococci
      concentrations decreased significantly (P < 0.05). However, 11 C-BPTs (55.5% of
      isolates) persisted across all sampling rounds. E. casseliflavus and E. mundtii
      were the most common enterococci populations comprising of >57% of all isolates.
      Ten of the 11 most dominant C-BPTs were resistant to multiple antibiotics and
      harboured one or more VGs. The high prevalence of antibiotic resistance and VGs
      among enterococci isolates in this catchment not only provides them with niche
      advantages but also poses a risk to public health.

PMID- 29040073
TI  - Removal of model viruses, E. coli and Cryptosporidium oocysts from surface water
      by zirconium and chitosan coagulants.
AB  - The present work evaluates the effect of contact filtration, preceded by
      coagulation with zirconium (Zr) and chitosan coagulants, on model microorganisms
      and waterborne pathogens. River water intended for potable water production was
      spiked with MS2 and Salmonella Typhimurium 28B bacteriophages, Escherichia coli,
      and Cryptosporidium parvum oocysts prior to coagulation. The hygienic performance
      demonstrated by Zr comprised 3.0-4.0 log10 removal of viruses and 5.0-6.0 log10
      removal of E. coli and C. parvum oocysts. Treatment with chitosan resulted in a
      removal of 2.5-3.0 log10 of viruses and parasites, and 4.5-5.0 log10 of bacteria.
      A reference coagulant, polyaluminium chloride (PACl), gave a 2.5-3.0 log10
      removal of viruses and 4.5 log10 of E. coli. These results indicate that both Zr
      and chitosan enable adequate removal of microorganisms from surface water. The
      present study also attempts to assess removal rates of the selected
      microorganisms with regard to their size and surface properties. The isoelectric
      point of the Salmonella Typhimurium 28B bacteriophage is reported for the first
      time. The retention of the selected microorganisms in the filter bed appeared to
      have some correlation with their size, but the effect of the charge remained
      unclear.

PMID- 29040074
TI  - Use of non-linear mixed-effects modelling and regression analysis to predict the
      number of somatic coliphages by plaque enumeration after 3 hours of incubation.
AB  - The present study aimed to establish the kinetics of the appearance of coliphage
      plaques using the double agar layer titration technique to evaluate the
      feasibility of using traditional coliphage plaque forming unit (PFU) enumeration
      as a rapid quantification method. Repeated measurements of the appearance of
      plaques of coliphages titrated according to ISO 10705-2 at different times were
      analysed using non-linear mixed-effects regression to determine the most suitable
      model of their appearance kinetics. Although this model is adequate, to simplify
      its applicability two linear models were developed to predict the numbers of
      coliphages reliably, using the PFU counts as determined by the ISO after only 3
      hours of incubation. One linear model, when the number of plaques detected was
      between 4 and 26 PFU after 3 hours, had a linear fit of: (1.48 * Counts3 h +
      1.97); and the other, values >26 PFU, had a fit of (1.18 * Counts3 h + 2.95). If
      the number of plaques detected was <4 PFU after 3 hours, we recommend incubation
      for (18 +/- 3) hours. The study indicates that the traditional coliphage plating
      technique has a reasonable potential to provide results in a single working day
      without the need to invest in additional laboratory equipment.

PMID- 29040075
TI  - Development of recreational water spray ground design regulations in New York
      State, an engineering approach.
AB  - The New York State Department of Health developed regulations for the design and
      operation of spray grounds to address the potential for recreational water
      illnesses associated with this type of venue. The water treatment component of
      the new regulation was based on a first-principles approach to address the unique
      challenges of spray grounds. The regulation departs from traditional recreational
      water treatment methods by requiring a novel filtration approach and the
      installation of UV disinfection. The water treatment system was also required to
      incorporate automatic control systems to ensure the water quality is maintained
      with a minimum of operator involvement. The treatment process specifications were
      based on pathogen and contaminant loadings that are likely to be encountered at
      spray grounds. The regulation was finalized in 2007, giving New York State a
      reliable means of protecting the health of spray ground patrons.

PMID- 29040076
TI  - Total coliform and Escherichia coli contamination in rural well water: analysis
      for passive surveillance.
AB  - With increasing stress on our water resources and recent waterborne disease
      outbreaks, understanding the epidemiology of waterborne pathogens is crucial to
      build surveillance systems. The purpose of this study was to explore techniques
      for describing microbial water quality in rural drinking water wells, based on
      spatiotemporal analysis, time series analysis and relative risk mapping. Tests
      results for Escherichia coli and coliforms from private and small public well
      water samples, collected between 2004 and 2012 in Alberta, Canada, were used for
      the analysis. Overall, 14.6 and 1.5% of the wells were total coliform and E. coli
      positive, respectively. Private well samples were more often total coliform or E.
      coli-positive compared with untreated public well samples. Using relative risk
      mapping we were able to identify areas of higher risk for bacterial contamination
      of groundwater in the province not previously identified. Incorporation of time
      series analysis demonstrated peak contamination occurring for E. coli in July and
      a later peak for total coliforms in September, suggesting a temporal dissociation
      between these indicators in terms of groundwater quality, and highlighting the
      potential need to increase monitoring during certain periods of the year.

PMID- 29040077
TI  - Influence of pathogenic bacterial activity on growth of Scenedesmus sp. and
      removal of nutrients from public market wastewater.
AB  - The present study aims to investigate the influence of Staphylococcus aureus,
      Escherichia coli and Enterococcus faecalis in public market wastewater on the
      removal of nutrients in terms of ammonium (NH4-) and orthophosphate (PO43) using
      Scenedesmus sp. The removal rates of NH4- and orthophosphate PO43- and batch
      kinetic coefficient of Scenedesmus sp. were investigated. The phycoremediation
      process was carried out at ambient temperature for 6 days. The results revealed
      that the pathogenic bacteria exhibited survival potential in the presence of
      microalgae but they were reduced by 3-4 log at the end of the treatment process.
      The specific removal rates of NH4- and PO43- have a strong relationship with
      initial concentration in the public market wastewater (R2 = 0.86 and 0.80,
      respectively). The kinetic coefficient of NH4- removal by Scenedesmus sp. was
      determined as k = 4.28 mg NH4- 1 log10 cell mL-1 d-1 and km = 52.01 mg L-1 (R2 =
      0.94) while the coefficient of PO43- removal was noted as k = 1.09 mg NH4- 1
      log10 cell mL-1 d-1 and km = 85.56 mg L-1 (R2 = 0.92). It can be concluded that
      Scenedesmus sp. has high competition from indigenous bacteria in the public
      market wastewater to remove nutrients, with a higher coefficient of removal of
      NH4- than PO43.

PMID- 29040078
TI  - Genetic diversity of Escherichia coli isolates from surface water and groundwater
      in a rural environment.
AB  - The genetic characteristics among Escherichia coli strains can be grouped by
      origin of isolation. Then, it is possible to use the genotypes as a tool to
      determine the source of water contamination. The aim of this study was to define
      water aptitude for human consumption in a rural basin and to assess the diversity
      of E. coli water populations. Thus, it was possible to identify the main sources
      of fecal contamination and to explore linkages with the hydrogeological
      environment and land uses. The bacteriological analysis showed that more than 50%
      of samples were unfit for human consumption. DNA fingerprinting analysis by BOX
      PCR indicated low genotypic diversity of E. coli isolates taken from surface
      water and groundwater. The results suggested the presence of a dominant source of
      fecal contamination. The relationship between low genotypic diversity and land
      use would prove that water contamination comes from livestock. The genetic
      diversity of E. coli isolated from surface water was less than that identified in
      groundwater because of the different hydraulic features of both environments.
      Furthermore, each one of the two big strain groups identified in this basin is
      located in different sub-basins, showing that hydrological dynamics exerts
      selective pressure on bacteria DNA.

PMID- 29040079
TI  - Identification of nontuberculous mycobacteria isolated from hospital water by
      sequence analysis of the hsp65 and 16S rRNA genes.
AB  - Nontuberculous mycobacteria (NTM) have emerged as an important cause of
      opportunistic nosocomial infections. NTM has frequently been isolated from
      hospital water distribution systems. The aim of this study was to survey the risk
      of NTM infections and determine the prevalence of NTM species in the hospital
      water distribution systems in Tabriz, Iran. One hundred and twenty samples of
      water from different sources of Tabriz hospitals were collected. The samples were
      filtered through 0.45-um pore size membranes and decontaminated with 0.01%
      cetylpyridinium chloride. The sediment was inoculated onto Lowenstein-Jensen
      medium and incubated for 8 weeks. For identification to the species level,
      partial sequence analysis of the hsp65 and 16S rRNA genes were used. NTM were
      detected in 76 (63.3%) of 120 samples. Potentially pathogenic mycobacteria and
      saprophytic mycobacteria were isolated. Mycobacterium gordonae was the only
      single species that was present in all types of water. The prevalence of NTM in
      Tabriz hospitals' water compared with many investigations on hospital waters was
      high. This indicates that the immunocompromised patients and transplant
      recipients are at risk of contamination which necessitates considering
      decontamination of water sources to prevent such potential hazards.

PMID- 29040080
TI  - Detection of Giardia intestinalis in water samples collected from natural water
      reservoirs and wells in northern and north-eastern Poland using LAMP, real-time
      PCR and nested PCR.
AB  - Giardia intestinalis is a protozoan parasite, transmitted to humans and animals
      by the faecal-oral route, mainly through contaminated water and food. Knowledge
      about the distribution of this parasite in surface water in Poland is fragmentary
      and incomplete. Accordingly, 36 environmental water samples taken from surface
      water reservoirs and wells were collected in Pomerania and Warmia-Masuria
      provinces, Poland. The 50 L samples were filtered and subsequently analysed with
      three molecular detection methods: loop-mediated isothermal amplification (LAMP),
      real-time polymerase chain reaction (real-time PCR) and nested PCR. Of the
      samples examined, Giardia DNA was found in 15 (42%) samples with the use of LAMP;
      in 12 (33%) of these samples, Giardia DNA from this parasite was also detected
      using real-time PCR; and in 9 (25%) using nested PCR. Sequencing of selected
      positive samples confirmed that the PCR products were fragments of the Giardia
      intestinalis small subunit rRNA gene. Genotyping using multiplex real-time PCR
      indicated the presence of assemblages A and B, with the latter predominating. The
      results indicate that surface water in Poland, as well as water taken from
      surface wells, may be a source of Giardia strains which are potentially
      pathogenic for humans. It was also demonstrated that LAMP assay is more sensitive
      than the other two molecular assays.

PMID- 29040081
TI  - Characterization of extended spectrum beta-lactamase (ESBL)-producing Escherichia
      coli in Asi (Orontes) River in Turkey.
AB  - In this study, the presence of extended spectrum beta-lactamase (ESBL)-producing
      Escherichia coli in aquatic environments (the Orontes River and an urban
      wastewater) was investigated. Fifty-four E. coli strains resistant to cefotaxime
      were isolated from the river waters and nearby waste water treatment plant and
      screened for ESBL gene variants, different classes of integrons and sulfonamide
      resistance genes. The ESBL-producing E. coli strains were further characterized
      by PhP-typing system, phylogenetic grouping and antimicrobial susceptibility
      testing. Of the 54 ESBL-producing strains, 14 (25.9%) belonged to four common PhP
      types and the remaining were of single types. CTX-M type ESBL genes were
      identified in 68% of the isolates. The most predominant specific CTX-M subtype
      identified was blaCTX-M-15 (n = 36), followed by blaCTX-M-1 (n = 1). None of the
      isolates were SHV and OXA positive. Most of the ESBL positive isolates (n = 37;
      68.5%) were harboring sul gene. This study indicates a widespread distribution of
      CTX-M-15 producing E. coli strains in the surface waters in part of Turkey,
      suggesting an aquatic reservoir for ESBL genes.

PMID- 29040082
TI  - Determinants of the use of alternatives to arsenic-contaminated shallow
      groundwater: an exploratory study in rural West Bengal, India.
AB  - Shallow groundwater containing toxic concentrations of arsenic is the primary
      source of drinking water for millions of households in rural West Bengal, India.
      Often, this water also contains unpleasant levels of iron and non-negligible
      fecal contamination. Alternatives to shallow groundwater are increasingly
      available, including government-built deep tubewells, water purchased from
      independent providers, municipal piped water, and household filters. We conducted
      a survey of 501 households in Murshidabad district in 2014 to explore what
      influenced the use of available alternatives. Socioeconomic status and the
      perceived likelihood of gastrointestinal (GI) illness (which was associated with
      dissatisfaction with iron in groundwater) were the primary determinants of the
      use of alternatives. Arsenic knowledge was limited. The choice amongst
      alternatives was influenced by economic, social, and aesthetic factors, but not
      by health risk perceptions. The use of purchased water was rarely exclusive and
      was strongly associated with socioeconomic status, suggesting that this form of
      market-based water provision does not ensure universal access. Demand for
      purchased water appeared to decrease significantly shortly after free piped water
      became available at public taps. Our results suggest that arsenic mitigation
      interventions that also address co-occurring water problems (iron, GI illness)
      could be more effective than a focus on arsenic alone.

PMID- 29040083
TI  - Consumption of edible ice contaminated with Acinetobacter, Pseudomonas, and
      Stenotrophomonas is a risk factor for fecal colonization with extended-spectrum
      beta-lactamase-producing Escherichia coli in Vietnam.
AB  - Although Vietnamese residents frequently harbor extended-spectrum beta-lactamase
      producing Escherichia coli (ESBL-E), it is unclear which foods/beverages are risk
      factors for acquiring these bacteria. The aim of this study was to evaluate the
      frequency with which edible ice served in restaurants is contaminated with
      antibiotic-resistant bacteria, and thereby clarify whether this product poses a
      risk for ESBL-E carriage in humans. Ice from restaurants in Vietnam and Japan was
      screened for bacteria capable of growing on agar containing cefotaxime (BG-CTX).
      Of the 119 BG-CTX strains isolated in Vietnam, 40%, 39%, and 12% were identified
      as Pseudomonas spp., Acinetobacter spp., and Stenotrophomonas maltophilia,
      respectively. Meanwhile, of the six such strains isolated in Japan, five were
      identified as Acinetobacter spp. and one as Pseudomonas spp. More than 10% of the
      Acinetobacter isolates exhibited cefotaxime, ceftazidime, and sulfa/trimethoprim
      resistance, while 21% of Pseudomonas and 14% of S. maltophilia isolates exhibited
      meropenem and sulfa/trimethoprim resistance, respectively. Subsequent multiplex
      polymerase chain reaction (PCR) analyses detected ESBL-encoding genes in 10% of
      the BG-CTX. Notably, feces harvested from mice administered water contaminated
      with BG-CTX contained E. coli harboring the blaCTX-M-9 gene. In conclusion, our
      findings indicate that consumption of contaminated edible ice is a risk factor
      for human ESBL-E carriage.

PMID- 29040084
TI  - Quantification and identification of aerobic bacteria in holy water samples from
      a German environment.
AB  - Despite its frequent use in many religious institutions, the microbiological
      quality of holy water is clearly underinvestigated. We analyzed the microbial
      load of 54 holy water samples, repeatedly taken in five Roman Catholic churches
      in the greater area of Villingen-Schwenningen, Germany, by means of aerobic
      colony counting and Matrix-Assisted Laser Desorption/Ionization (MALDI) Biotyping
      of representative isolates. Over all samples, colony counting indicated an
      average aerobic microbial load of 5.85 +/- 3.98 * 103 colony forming units (CFU)
      ml-1 (average +/- standard error of the mean (SEM)). Urban churches showed
      significantly higher contaminations than rural churches, probably owing to a
      greater number of visitors. Out of 145 bacterial isolates, 63 (43%) were
      identified to genus level and 39 (27%) to species level. The majority of the
      identified bacteria were typical human skin commensals, mainly affiliated with
      the genus Staphylococcus. Ten out of 20 (50%) of the identified species were
      classified as potential pathogens. Appropriate hygiene measures should be taken
      to control microbial contamination of holy water, e.g., regular water exchange,
      particularly in highly frequented churches.

PMID- 29040085
TI  - Sources of pharmaceuticals and personal care products in swimming pools.
AB  - Pharmaceuticals and personal care products (PPCPs) in swimming pool water are
      hypothesized to originate from fill water and anthropogenic sources like urine,
      sweat, swimwear and body surfaces. However, research exploring PPCP origins in
      pools is lacking. This research investigates PPCP sources at 31 swimming pools.
      Pool water was analyzed for 24 representative PPCPs using advanced liquid
      chromatography-mass spectrometry techniques. Fill water was analyzed as a
      contamination source and to determine if swimmers introduce PPCPs to pools.
      Results show every PPCP in fill water was present in pools except one, suggesting
      fill water is a PPCP source at pools. The presence of the antidepressant
      fluoxetine in 26% of pools and 0% of fill water indicates swimmers introduce
      pharmaceuticals. The flame retardant (tris(2-carboxyethyl)phosphine (TCEP)) was
      present 48% more frequently in pool than fill water, suggesting TCEP is
      introduced by body surfaces or swimwear. Enforcing showering and bathroom breaks
      is recommended to reduce PPCP contamination from swimmers.

PMID- 29040086
TI  - Compliance of brown mussel (Perna perna) production areas in the South of Brazil
      with the bacteriological criteria of the shellfish hygiene systems in the
      European Union and United States of America: assessing the impacts on consumer
      safety.
AB  - Levels of faecal indicator organisms (FIOs) monitored in surface water and brown
      mussels collected at 28 production areas in Brazil from August 2012 to October
      2013 were used to assess compliance with the bacteriological standards of the
      shellfish hygiene classification systems used in the European Union (EU) and USA.
      This classification determines the level of post-harvesting purification needed
      to reduce the risk of illness in consumers. The results indicate that 36% of
      production areas would be class A under the EU system and 75% would be 'Approved'
      under the US system. Mathematical models showed that a 90th percentile of FIO
      levels in water of 43 MPN (most probable number) 100 mL-1 (standard for
      'Approved' areas under the US system) would correspond to an 80th percentile of
      FIO levels in mussels of 572 MPN 100 g-1. This concentration is more than double
      that in the class A standard in the EU system. These results have important
      implications for public health since no post-harvesting purification is required
      for any of these classification categories. Areas compliant with the US
      'Restricted' and EU class B standards, however, provide similar levels of
      consumer safety.

PMID- 29040099
TI  - Muscle Relaxation and Lower Airway Characteristics May Affect Tidal Volume during
      Pressure-controlled Ventilation.

PMID- 29040100
TI  - Rocuronium Onset May Affect Mask Ventilation.

PMID- 29040101
TI  - "Loose Lips Are Actually Good".

PMID- 29040102
TI  - In Reply.

PMID- 29040103
TI  - Insulin for Perioperative Glucose Control: Settled Science?

PMID- 29040104
TI  - In Reply.

PMID- 29040105
TI  - When Managing Patients with Left Ventricular Assist Devices Undergoing Noncardiac
      Surgery, Less Is Not More.

PMID- 29040106
TI  - Noninvasive Blood Pressure Determination in Left Ventricular Assist Device
      Patients.

PMID- 29040107
TI  - In Reply.

PMID- 29040108
TI  - A Deeper Look at Anesthesia Depth.

PMID- 29040109
TI  - Amendments and Corrections to Mattusch et al. (Anesthesiology 2015; 122[5]: 1047
      59), "Impact of Hyperpolarization-activated, Cyclic Nucleotide-gated Cation
      Channel Type 2 for the Xenon-mediated Anesthetic Effect: Evidence from In Vitro
      and In Vivo Experiments".

PMID- 29040111
TI  - Healing Oncology Nurses in a Caring Environment.

PMID- 29040110
TI  - Racial Differences in Palliative Care Use After Stroke in Majority-White,
      Minority-Serving, and Racially Integrated U.S. Hospitals.
AB  - OBJECTIVES: Racial/ethnic differences in palliative care resource use after
      stroke have been recognized, but it is unclear whether patient or hospital
      characteristics drive this disparity. We sought to determine whether palliative
      care use after intracerebral hemorrhage and ischemic stroke differs between
      hospitals serving varying proportions of minority patients. DESIGN: Population
      based cross-sectional study. SETTING: Inpatient hospital admissions from the
      Nationwide Inpatient Sample between 2007 and 2011. PATIENTS: A total of 46,735
      intracerebral hemorrhage and 331,521 ischemic stroke cases. INTERVENTIONS:
      Palliative care use. MEASUREMENTS AND MAIN RESULTS: Intracerebral hemorrhage and
      ischemic stroke admissions were identified from the Nationwide Inpatient Sample
      between 2007 and 2011. Hospitals were categorized based on the percentage of
      ethnic minority stroke patients (< 25% minorities ["white hospitals"], 25-50%
      minorities ["mixed hospitals"], or > 50% minorities ["minority hospitals"]).
      Logistic regression was used to evaluate the association between race/ethnicity
      and palliative care use within and between the different hospital strata. Stroke
      patients receiving care in minority hospitals had lower odds of palliative care
      compared with those treated in white hospitals, regardless of individual patient
      race/ethnicity (adjusted odds ratio, 0.65; 95% CI, 0.50-0.84 for intracerebral
      hemorrhage and odds ratio, 0.62; 95% CI, 0.50-0.77 for ischemic stroke). Ethnic
      minorities had a lower likelihood of receiving palliative care compared with
      whites in any hospital stratum, but the odds of palliative care for both white
      and minority intracerebral hemorrhage patients was lower in minority compared
      with white hospitals (odds ratio, 0.66; 95% CI, 0.50-0.87 for white and odds
      ratio, 0.64; 95% CI, 0.46-0.88 for minority patients). Similar results were
      observed in ischemic stroke. CONCLUSIONS: The odds of receiving palliative care
      for both white and minority stroke patients is lower in minority compared with
      white hospitals, suggesting system-level factors as a major contributor to
      explain race disparities in palliative care use after stroke.

PMID- 29040112
TI  - Interventions for the Management of Fatigue in Adults With a Primary Brain Tumor:
      A Cochrane Systematic Review Summary.

PMID- 29040113
TI  - Investigating Language of Fear and Failure in Cancer Care.

PMID- 29040114
TI  - Association of Adverse Childhood Experiences with Co-occurring Health Conditions
      in Early Childhood.
AB  - OBJECTIVE: To understand how adverse childhood experiences (ACEs) are associated
      with co-occurring physical, mental and developmental problems during early
      childhood. METHOD: A subsample of 19,957 children aged 2-5 years were selected
      from the 2011-2012 National Survey for Child Health. Outcomes included 18 health
      conditions organized in singular condition domains (physical, mental, and
      developmental), and combinations of condition domains (e.g., physical plus
      mental, mental plus developmental, etc.). Predictors included 8 ACEs (divorce of
      a parent, death of a parent, exposure to domestic violence, living with someone
      with a drug or alcohol abuse problem, household member with a mental illness,
      parent incarceration, neighborhood violence, discrimination). Multivariable
      logistic regression was performed controlling for demographic characteristics,
      having a personal doctor, health insurance coverage, and seeing a health care
      professional in the previous year. RESULTS: Experiencing 3 or more ACEs before
      the age of 5 years was associated with increased likelihood of nearly every co
      occurring condition combination across 3 domains of health. Most notably,
      experiencing 3 or more ACEs was also associated with a 2-fold increase in
      likelihood of having >=1 physical condition and >=1 developmental condition, a 9
      fold increase in likelihood of having >=1 mental and >=1 developmental condition,
      and a 7-fold increase in likelihood of having >=1 physical, >=1 mental, and >=1
      developmental condition. CONCLUSION: This study demonstrates that we can identify
      the health effects of adversity quite early in development and that management
      should include communication between both health care and early childhood
      education providers.

PMID- 29040115
TI  - Keratitis After Post-Kala-Azar Dermal Leishmaniasis.
AB  - PURPOSE: To report 2 cases of keratitis occurring after post-kala-azar dermal
      leishmaniasis (PKDL) in immunocompetent patients. METHODS: Case report and
      literature review. RESULTS: Two male patients presented with a dense stromal
      infiltrate in the temporal and superior aspects of the cornea, respectively.
      Microbiological workup in both patients did not show any offending organism. Both
      patients were undergoing treatment for PKDL in the form of oral miltefosine.
      After careful deliberation, topical prednisolone was started under antibiotic
      cover for both patients with close follow-up. There was a dramatic improvement
      with resolution of the infiltrate and a good visual outcome. CONCLUSIONS: We
      present the first reported cases of keratitis after PKDL, which responded to
      topical corticosteroid therapy. The treating clinician must be made aware of such
      a presentation of leishmaniasis especially in endemic areas.

PMID- 29040116
TI  - Air Versus Sulfur Hexafluoride Gas Tamponade in Descemet Membrane Endothelial
      Keratoplasty: A Fellow Eye Comparison.
AB  - PURPOSE: To perform a fellow eye comparison of outcomes and complications when
      using air or sulfur hexafluoride (SF6) gas as a tamponade in Descemet membrane
      endothelial keratoplasty (DMEK). METHODS: One hundred thirty-six eyes of 68
      consecutive patients who underwent uneventful DMEK in both eyes for Fuchs
      endothelial corneal dystrophy were included in this retrospective study.
      Inclusion criteria were air tamponade (80% of the anterior chamber volume) in the
      first eye and 20% SF6 gas tamponade (80% of the anterior chamber volume) in the
      second eye; and same donor tissue culture condition in both eyes. All eyes
      received laser iridotomy on the day before DMEK. Main outcome measures included
      preoperative and postoperative best-corrected visual acuity, endothelial cell
      density, corneal volume, rebubbling rate, and rate of postoperative pupillary
      block caused by the air/gas bubble. RESULTS: Thirteen of 68 eyes (19.1%) with an
      air tamponade needed rebubbling compared with 4 of 68 eyes (5.9%) with an SF6 gas
      tamponade (P = 0.036). Postoperative pupillary block necessitating partial
      release of air/gas occurred in 1 eye (1.5%) with an air tamponade and 3 eyes
      (4.4%) with an SF6 gas tamponade (P = 0.301). There were no significant
      differences in preoperative and postoperative best-corrected visual acuity,
      endothelial cell density, and corneal volume within 3-month follow-up.
      CONCLUSIONS: Our results confirm the previously reported better graft adhesion
      when using an SF6 gas tamponade in DMEK without increased endothelial cell
      toxicity. The rate of pupillary block in eyes with an SF6 gas tamponade was
      comparable to that with an air tamponade. As a consequence, we recommend using
      SF6 gas as the tamponade in DMEK.

PMID- 29040117
TI  - Factors Limiting the Visual Outcome After Descemet Stripping Automated
      Endothelial Keratoplasty: Comprehensive Analysis Including the Graft Position and
      Irregularity.
AB  - PURPOSE: To investigate factors affecting best postoperative corrected distance
      visual acuity (CDVA) in patients who have undergone Descemet stripping automated
      endothelial keratoplasty (DSAEK). METHODS: Forty-two eyes of 42 patients with
      predominantly non-Fuchs endothelial corneal dystrophy after DSAEK were
      retrospectively evaluated. All patients were examined using anterior segment
      optical coherence tomography when their best postoperative CDVA had been
      achieved. We analyzed the relationship between best postoperative CDVA and
      preoperative, intraoperative, and postoperative factors, including corneal higher
      order aberrations (HOAs), corneal backward scattering, graft irregularity, and
      graft decentration. Variables with P < 0.2 in univariate analysis were entered
      into a multivariate linear regression model to determine the factors affecting
      best postoperative CDVA. RESULTS: Mean CDVA improved from 1.16 +/- 0.46
      preoperatively to 0.22 +/- 0.19 logarithm of the minimum angle of resolution
      equivalents postoperatively (P < 0.0001). Best postoperative CDVA was achieved
      11.6 +/- 7.7 months after DSAEK. Multivariate analysis showed that anterior
      corneal coma-like HOAs and venting incisions inside the pupil area were
      significantly correlated with best postoperative CDVA (t = 2.90, P = 0.006; t =
      2.62, P = 0.01, respectively). No significant relationship was found between the
      visual outcome and any other factor, including posterior corneal HOAs, corneal
      backward scattering, graft decentration, and graft irregularity. CONCLUSIONS:
      Irregularity of the anterior corneal surface and venting incisions inside the
      pupil area are important factors that impair best postoperative CDVA in patients
      who have undergone DSAEK. In contrast, our results indicate that the graft
      position and irregularity might not have a strong influence on the visual outcome
      after DSAEK.

PMID- 29040118
TI  - Influence of Socioeconomic Deprivation on Visual Acuity in Patients Undergoing
      Corneal Transplantation.
AB  - PURPOSE: To determine whether there is an association between socioeconomic
      status and best-corrected visual acuity (BCVA) in patients undergoing corneal
      transplantation in the United Kingdom. METHODS: Retrospective cohort study of
      4306 patients registered on the national United Kingdom Transplant Registry and
      undergoing penetrating keratoplasty, anterior lamellar keratoplasty, or
      endothelial keratoplasty in 2002, 2008, and 2013. Socioeconomic status was
      determined by applying a validated deprivation index to generate a score based on
      5 categories. Patients' demographic details, preoperative BCVA, copathology,
      surgical center volume, and socioeconomic status were analyzed for univariate
      effects of categorical and continuous variables. Binary logistic regression was
      used to determine whether preoperative BCVA was affected by socioeconomic status
      after adjusting for other factors. RESULTS: A larger percentage of the most
      deprived group was female in each period compared with the least deprived, but
      this was only significant in 2002 (48.7% vs. 40.3%; P = 0.04). There was no
      interaction between socioeconomic status and the preoperative BCVA in the grafted
      eye. However, BCVA in the fellow eye was poorer for the most economically
      deprived patients compared with the least deprived in 2013 (P = 0.01).
      CONCLUSIONS: We found no evidence of a relationship between socioeconomic
      deprivation and BCVA in the transplant recipient eye. However, there was clear
      evidence of an association between socioeconomic deprivation and reduced acuity
      in fellow eyes, for which barriers to access or low patient demand may be
      possible contributors.

PMID- 29040119
TI  - Prospective Clinical Trial of Corneal Reconstruction With Biomaterial-Free
      Cultured Oral Mucosal Epithelial Cell Sheets.
AB  - PURPOSE: To investigate the efficacy and safety of transplantation with
      biomaterial-free cultured oral mucosal epithelial cell sheets (COMECs) for ocular
      reconstruction in subjects with total limbal stem cell deficiency. METHODS: A
      prospective clinical trial (NCT02149732) was conducted in 8 subjects with total
      limbal stem cell deficiency after approval from the institutional review board of
      Seoul National University Hospital (H-0707-043-213) and the Ministry of Food and
      Drug Safety of Korea. COMECs were prepared in a culture system without the use of
      any temperature-sensitive polymers or carriers. The COMECs were transplanted
      without suture fixation. Four subjects underwent penetrating keratoplasty after
      stabilization of the COMEC transplant. Stable epithelialization, changes in
      visual acuity, and postoperative complications were evaluated for 6 months.
      Corneal cytokeratins (K) of 4 subjects who underwent penetrating keratoplasty
      were stained with an immunofluorescent agent. RESULTS: The ocular surface was
      successfully reconstructed in 6 eyes. Complete stable epithelialization was
      achieved within a mean of 53.6 days. Visual improvement (>=2 lines) was achieved
      in 62.5% of the eyes. K12 (corneal phenotype), K4, and K13 (mucosal phenotype)
      were well expressed in grafts after keratoplasty, whereas K1, K8, and K19 were
      barely expressed. No ocular infections, local tumor formation, or remarkable
      systemic complications were observed. Ocular reconstruction using COMECs failed
      in 2 eyes, which had full symblepharon in 4 quadrants. CONCLUSIONS: Transplanting
      biomaterial-free COMECs seems to be an efficient and safe procedure to
      reconstruct the ocular surface in patients who are completely limbal stem cell
      deficient without a full symblepharon.

PMID- 29040120
TI  - Comparative Evaluation of Tacrolimus Versus Interferon Alpha-2b Eye Drops in the
      Treatment of Vernal Keratoconjunctivitis: A Randomized, Double-Masked Study.

PMID- 29040121
TI  - Outcomes and Rationale of Excision and Mucous Membrane Grafting in Palpebral
      Vernal Keratoconjunctivitis.
AB  - PURPOSE: To report outcomes of mucous membrane grafting (MMG) for refractory
      giant papillae in vernal keratoconjunctivitis. METHODS: Eleven eyes of 6 patients
      having giant papillae and recurrent shield ulcers refractory to topical
      medications, cryotherapy, and supratarsal steroid injections and shave excision
      of papillae underwent surgical resection of the giant papillae with MMG. Average
      occurrence of shield ulcers was twice per eye per year before the procedure with
      50% of eyes having steroid-induced cataract and glaucoma. RESULTS: No recurrence
      of the shield ulcer in any eye was observed over a mean follow-up period of 38.2
      (range 9-106) months. The papillae recurred beyond the graft junction in one eye.
      CONCLUSIONS: Surgical excision of refractory giant papillae followed by MMG does
      have its advantages in reducing their corneal complications, and it should be
      considered early in the management of exuberant refractory giant papillae.

PMID- 29040122
TI  - Treatment and Resolution of Filamentary Keratitis in a Patient with Stiff Person
      Syndrome.
AB  - PURPOSE: To report a rare case of filamentary keratitis associated with stiff
      person syndrome. METHODS: Case report. RESULTS: A 26-year-old woman with several
      autoimmune conditions was referred because of filamentary keratitis. Conservative
      management using lubrication, mucolytics, and bandage contact lenses failed to
      adequately relieve symptoms. Despite the addition of oral prednisone,
      cyclosporine, and azathioprine, the patient's condition persisted with numerous
      filaments and severe dry eye. One month later, the patient had an episode of
      sudden muscle cramps in her back, for which she was hospitalized. Investigations
      revealed a diagnosis of stiff person syndrome, positive for glutamic acid
      decarboxylase autoantibodies. Plasmapheresis and high-dose intravenous steroids
      were provided as initial therapy. On follow-up, her filamentary keratitis
      resolved and at the last visit, her ocular symptoms had completely resolved.
      CONCLUSIONS: Filamentary keratitis is a chronic, recurrent condition that can be
      challenging to treat. Effective management requires careful consideration of
      possible predisposing causes, especially in refractory cases.

PMID- 29040123
TI  - Reply.

PMID- 29040124
TI  - Highly Cross-Linked Polyethylene Reduces Wear and Revision Rates in Total Hip
      Arthroplasty: A 10-Year Double-Blinded Randomized Controlled Trial.
AB  - BACKGROUND: Highly cross-linked polyethylene (XLPE) was developed to address the
      problem of wear and osteolysis associated with metal-on-conventional ultra-high
      molecular weight polyethylene (UHMWPE) bearing surfaces. The purpose of this
      study was to compare in vivo wear rates and clinical and radiographic outcomes
      between XLPE and UHMWPE in a prospective double-blinded randomized controlled
      trial with a minimum of 10 years of follow-up. METHODS: We randomized 122
      patients to receive either a conventional UHMWPE liner (Enduron; DePuy) or an
      XLPE liner (Marathon; DePuy). Ninety-one patients were assessed clinically and
      radiographically at a minimum of 10 years (range, 10.08 to 12.17 years). Oxford
      Hip Scores and Short Form-12 Health Survey scores were collected. The radiographs
      were analyzed for osteolysis and for 2-dimensional (2-D), 3-dimensional (3-D),
      and volumetric wear using validated software. RESULTS: All 122 patients were
      accounted for at the 10-year follow-up evaluation. Twelve patients had undergone
      revision surgery, 21 patients had died (1 of whom had previously undergone
      revision surgery), and 2 patients were unable to return for follow-up, leaving 91
      patients available for clinical and radiographic evaluation. At a minimum of 10
      years, 3-D wear rates were significantly lower (p < 0.001) in the XLPE group
      (mean, 0.03 mm/yr) than in the conventional UHMWPE group (mean, 0.27 mm/yr). The
      prevalence of osteolysis was also significantly lower in the XLPE group (38%
      versus 8%, p < 0.005), as was the revision rate (14.6% versus 1.9%, p = 0.012),
      with 10 of the 12 revisions being in the Enduron group. There was no significant
      difference between the clinical scores of the 2 groups. CONCLUSIONS: XLPE liners
      have significantly reduced wear and are associated with a greater implant
      survival rate at 10 years compared with conventional UHMWPE liners. LEVEL OF
      EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 29040125
TI  - Minimal Incision Total Hip Arthroplasty: A Concise Follow-up Report on Functional
      and Radiographic Outcomes at 10 Years.
AB  - : In 2005, we conducted a prospective randomized controlled trial that
      demonstrated that, compared with a standard incision, a minimal incision
      technique did not improve early outcomes of total hip arthroplasty (THA). There
      was concern that reduced exposure could compromise long-term outcome. For the
      current study, all surviving participants were invited to return for 10-year
      radiographic and clinical evaluation. Outcome scores were available for 152
      patients (69.4%) from the original cohort, and radiographs were available for 126
      (57.5%). The median duration of follow-up was 124 months. We did not find
      significant differences in functional status or radiographic outcome between the
      minimal and standard incision groups at 10 years. The 10-year implant survival
      rate was 99.1% (95% confidence interval [CI] = 97.3% to 100%) in the standard
      incision group and 97.9% (95% CI = 95.1% to 100%) in the minimal incision group
      (p = 0.57). We concluded that minimal incision THA performed by a high-volume
      surgeon does not compromise long-term results but offers no benefit over a
      standard incision. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 29040126
TI  - Reverse Total Shoulder Arthroplasty for Massive, Irreparable Rotator Cuff Tears
      Before the Age of 60 Years: Long-Term Results.
AB  - BACKGROUND: There has been serious concern regarding the longevity and durability
      of outcomes of reverse total shoulder arthroplasty (RTSA) in younger patients. It
      was the purpose of this study to analyze long-term outcomes and complications of
      RTSA for irreparable rotator cuff tears in patients younger than 60 years.
      METHODS: Twenty patients (23 shoulders) with a mean age of 57 years (range, 47 to
      59 years) were evaluated at a mean of 11.7 years (range, 8 to 19 years) after
      RTSA. Fifteen shoulders (65%) had undergone previous non-arthroplasty surgery.
      Longitudinal clinical and radiographic outcomes were assessed. RESULTS: At the
      time of final follow-up, the mean absolute and relative preoperative Constant
      score (CS) (and standard deviation) had improved from 24 +/- 9 to 59 +/- 19
      points (p < 0.001) and from 29% +/- 11% to 69% +/- 21% (p < 0.001), respectively.
      The mean Subjective Shoulder Value (SSV) had increased from 20% +/- 13% to 71% +/
      27% (p < 0.001). There were also significant improvements in the mean active
      anterior elevation (from 64 degrees  to 117 degrees ), active abduction (from 58
      degrees  to 111 degrees ), pain scores, and strength (all p <= 0.001). Clinical
      outcomes did not significantly deteriorate beyond 10 years and the functional
      results of patients with previous surgical procedures were not significantly
      inferior to the results of those with primary RTSA. The grade of, and number of
      patients with, radiographically apparent notching increased over time; the mean
      relative CS was lower in patients in whom the notching was grade 2 or higher
      (57%) than it was in those with no or grade-1 notching (81%; p = 0.006). Nine
      (39%) had >=1 complication, with 2 failed RTSAs (9%). CONCLUSIONS: RTSA in
      patients younger than 60 years leads to substantial subjective and functional
      improvement without clinical deterioration beyond 10 years. It is associated with
      a substantial complication rate, and complications compromise ultimate subjective
      and objective outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 29040127
TI  - Double-Row Arthroscopic Rotator Cuff Repair Is More Cost-Effective Than Single
      Row Repair.
AB  - BACKGROUND: The optimal technique for arthroscopic rotator cuff repair is
      controversial, and both single and double-row techniques are commonly used. In
      the current era of increasing costs, health-care delivery models are focusing on
      the value of care. In this study, we compared the cost-effectiveness of single
      row and double-row reconstructions in patients undergoing arthroscopic rotator
      cuff repair. METHODS: A cost-utility analysis was performed from the perspective
      of a publicly funded health-care system. Health-care costs, probabilities, and
      utility values were derived from the published literature. Efficacy data were
      obtained from a previous randomized controlled trial comparing the effect of
      single-row (n = 48) or double-row (n = 42) reconstruction among 90 surgical
      patients. Unit cost data were obtained from a hospital database and the Ontario
      Schedule of Benefits and Fees. Results are presented as an incremental cost per
      quality-adjusted life year (QALY) gained. All costs are presented in 2015
      Canadian dollars. A series of 1-way and probabilistic sensitivity analyses were
      performed. RESULTS: Double-row fixation was more costly ($2,134.41 compared with
      $1,654.76) but was more effective than the single-row method (4.073 compared with
      4.055 QALYs). An incremental cost-effectiveness ratio (ICER) was estimated to be
      $26,666.75 per QALY gained for double-row relative to single-row fixation. A
      subgroup analysis demonstrated that patients with larger rotator cuff tears (>=3
      cm) had a lower ICER, suggesting that double-row fixation may be more cost
      effective for larger tears. CONCLUSIONS: Based on the willingness-to-pay
      threshold of $50,000 per QALY gained, double-row fixation was found to be more
      cost-effective than single-row. Furthermore, a double-row reconstruction was
      found to be more economically attractive for larger rotator cuff tears (>=3 cm).
      LEVEL OF EVIDENCE: Economic and Decision Analysis Level IV. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 29040128
TI  - Single-Dose, Preoperative Vitamin-D Supplementation Decreases Infection in a
      Mouse Model of Periprosthetic Joint Infection.
AB  - BACKGROUND: Despite recent advances, infection remains the most common etiology
      of arthroplasty failure. Recent work suggests that 25-hydroxyvitamin D (25D)
      deficiency correlates with the frequency of periprosthetic joint infection (PJI).
      We endeavored to examine whether 25D3 deficiency leads to increased bacterial
      burden in vivo in an established mouse model of PJI and, if so, whether this
      effect can be reversed by preoperative 25D3 supplementation. METHODS: Mice (lys
      EGFP) possessing fluorescent neutrophils were fed a vitamin D3-sufficient (n =
      20) or deficient (n = 40) diet for 6 weeks. A group of 25D3-deficient mice (n =
      20) were "rescued" with 1 intraperitoneal dose of 25D3 at 3 days before surgery.
      A stainless steel implant was inserted into the knee joint and the joint space
      was inoculated with bioluminescent Staphylococcus aureus (1 * 10 colony forming
      units [CFUs]). In vivo imaging was used to monitor bacterial burden and
      neutrophil infiltration. Blood was drawn to confirm 25D3 levels 3 days before
      surgery and on postoperative days (PODs) 0 and 14. Mice were killed at POD 21,
      and CFUs were quantified after culture. Myeloperoxidase (MPO) and beta-N
      acetylglucosaminidase (NAG) were assayed to look at neutrophil infiltration and
      activated tissue macrophage recruitment, respectively. RESULTS: Serum values
      confirmed 25D3 deficiency and repletion of the 25D3-rescued group. Bacterial
      bioluminescence and neutrophil fluorescence were significantly greater (p < 0.05)
      in the 25D3-deficient group. CFU counts from the joint tissue and implant were
      also significantly greater in this group (p < 0.05). Rescue treatment
      significantly decreased bacterial burden and neutrophil infiltration (p < 0.05).
      Compared with the 25D3-sufficient and 25D3-rescued groups, MPO activity was
      higher (p < 0.02) and NAG activity was lower (p < 0.03) in the 25D3-deficient
      group. CONCLUSIONS: This study demonstrated in vivo in a mouse model of PJI that
      (1) 25D3 deficiency results in increased bacterial burden and neutrophil
      infiltration, and (2) this effect can be reversed with preoperative repletion of
      25D3. CLINICAL RELEVANCE: Considering that >65% of patients undergoing
      arthroplasty have insufficient or low levels of total 25D and that 25D levels can
      be replenished with ease using a U.S. Food and Drug Administration (FDA)
      approved, oral 25D3 product, 25D deficiency may be an important modifiable risk
      factor in humans undergoing joint replacement.

PMID- 29040129
TI  - Postoperative CT Is Superior for Acetabular Fracture Reduction Assessment and
      Reliably Predicts Hip Survivorship.
AB  - BACKGROUND: Postoperative pelvic radiographs are routinely used to assess
      acetabular fracture reduction. We compared radiographs and computed tomography
      (CT) with regard to their ability to detect residual fracture displacement. We
      also determined the association between the quality of reduction as assessed on
      CT and hip survivorship and identified risk factors for conversion to total hip
      arthroplasty (THA). METHODS: Patients were included in the study who had
      undergone acetabular fracture fixation between 1992 and 2012, who were followed
      for >=2 years (or until early THA), and for whom radiographs and a pelvic CT scan
      were available. Residual displacement was measured on postoperative radiographs
      and CT and graded according to Matta's criteria (0 to 1 mm indicating anatomic
      reduction; 2 to 3 mm, imperfect reduction; and >3 mm, poor reduction) by
      observers who were blinded to patient outcome. Kaplan-Meier survivorship curves
      were plotted and log-rank tests were used to assess statistical differences in
      survivorship curves between adequate (anatomic or imperfect) and inadequate
      reductions on CT. Cox proportional hazard regression analysis was used to
      identify risk factors for conversion to THA. Two hundred and eleven patients were
      included. At mean of 9.0 years (standard deviation [SD], 5.6; median, 7.9; range,
      0.5 to 23.3 years) postoperatively, 161 patients (76%) had retained their native
      hip. RESULTS: Compared with radiographs, CT showed worse reduction in 124 hips
      (59%), the same reduction in 79 (37%), and better reduction in 8 (4%). Of the 99
      patients graded as having adequate reduction on CT, 10% underwent conversion to
      THA in comparison with 36% of those with inadequate reduction, and there was a
      significant difference between the survivorship curves (p < 0.001). Mean hip
      survivorship was shorter in patients >=50 years of age (p < 0.001) and in those
      with an inadequate reduction on CT (p < 0.001). Independent risk factors for
      conversion to THA were age (hazard ratio [HR] = 4.46, 95% confidence interval
      [CI] = 2.07 to 9.62; p < 0.001), inadequate reduction (HR = 3.57, 95% CI = 1.71
      to 7.45; p = 0.001), and posterior wall involvement (HR = 1.81, 95% CI = 1.00 to
      3.26; p = 0.049). Sex, fracture type (elementary versus associated), and year of
      surgery did not influence hip survivorship. CONCLUSIONS: CT is superior to
      radiographs for detecting residual displacement after acetabular fracture
      fixation. Hip survivorship is greater in patients with adequate (anatomic or
      imperfect) reduction on CT. Along with older age and posterior wall involvement,
      an inadequate reduction on CT is a risk factor for conversion to THA. LEVEL OF
      EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 29040130
TI  - Volume-Outcome Relationship in Surgical Interventions for Spinal Metastases.
AB  - BACKGROUND: Surgery for spinal metastases is challenging and carries a high risk
      of perioperative morbidity and mortality. Procedures with such characteristics
      often exhibit a volume-outcome relationship. This has not been previously
      characterized for spinal metastasis surgery to our knowledge. METHODS: The
      Florida State Inpatient Database (2011 through 2014) was queried to identify
      patients who had undergone surgery for spinal metastases. Surgeon and hospital
      surgical volumes were compared with 90-day complication and readmission rates to
      develop procedural cut-points used to define high and low-volume providers. These
      were included in a multivariable logistic regression analysis that was adjusted
      for confounders. A separate analysis was performed to evaluate the effect of
      race/ethnicity and insurance status on the likelihood of receiving care from a
      high-volume surgeon or hospital. RESULTS: This study included 3,135 patients
      treated by 1,488 surgeons at 162 hospitals. Patients treated at low-volume
      hospitals had significantly higher odds of having postoperative complications
      (odds ratio [OR] = 1.47; 95% confidence interval [CI] = 1.13, 1.91) and
      readmissions (OR = 1.36; 95% CI = 1.06, 1.75). Those treated by low-volume
      surgeons also demonstrated a higher likelihood of complications (OR = 1.40; 95%
      CI = 1.16, 1.69) and readmissions (OR = 1.38; 95% CI = 1.17, 1.62). The
      likelihood of receiving intervention from a high-volume surgeon was significantly
      lower for African Americans (OR = 0.55; 95% CI = 0.41, 0.75) and Hispanics (OR =
      0.60; 95% CI = 0.44, 0.83). The odds of being treated at a high-volume hospital
      were also significantly lower for African Americans (OR = 0.58; 95% CI = 0.40,
      0.84) and Hispanics (OR = 0.28; 95% CI = 0.20, 0.38). CONCLUSIONS: There is a
      clear relationship between the volume and outcomes of surgical treatment of
      spinal metastases, with high-volume providers demonstrating reduced complication
      and readmission rates. Racial and ethnic minorities appear to experience health
      care segregation when it comes to surgical care for spinal metastases.
      Regionalization of care for these conditions may help improve access to high
      volume providers and mitigate disparities in care. LEVEL OF EVIDENCE: Therapeutic
      Level III. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 29040131
TI  - Acetabular Global Insufficiency in Patients with Down Syndrome and Hip-Related
      Symptoms: A Matched-Cohort Study.
AB  - BACKGROUND: The etiology of hip instability in Down syndrome is not completely
      understood. We investigated the morphology of the acetabulum and femur in
      patients with Down syndrome and compared measurements of the hips with those of
      matched controls. METHODS: Computed tomography (CT) images of the pelvis of 42
      patients with Down syndrome and hip symptoms were compared with those of 42 age
      and sex-matched subjects without Down syndrome or history of hip disease who had
      undergone CT for abdominal pain. Each of the cohorts had 23 male and 19 female
      subjects. The mean age (and standard deviation) in each cohort was 11.3 +/- 5.3
      years. The lateral center-edge angle (LCEA), acetabular inclination angle (IA),
      acetabular depth-width ratio (ADR), acetabular version, and anterior and
      posterior acetabular sector angles (AASA and PASA) were compared. The neck-shaft
      angle and femoral version were measured in the patients with Down syndrome only.
      The hips of the patients with Down syndrome were further categorized as stable (n
      = 21) or unstable (n = 63) for secondary analysis. RESULTS: The hips in the Down
      syndrome group had a smaller LCEA (mean, 10.8 degrees  +/- 12.6 degrees  compared
      with 25.6 degrees  +/- 4.6 degrees ; p < 0.0001), a larger IA (mean, 17.4 degrees
      +/- 10.3 degrees  compared with 10.9 degrees  +/- 4.8 degrees ; p < 0.0001), a
      lower ADR (mean, 231.9 +/- 56.2 compared with 306.8 +/- 31.0; p < 0.0001), a more
      retroverted acetabulum (mean acetabular version as measured at the level of the
      centers of the femoral heads [AVC], 7.8 degrees  +/- 5.1 degrees  compared with
      14.0 degrees  +/- 4.5 degrees ; p < 0.0001), a smaller AASA (mean, 55.0 degrees 
      +/- 9.9 degrees  compared with 59.7 degrees  +/- 7.8 degrees ; p = 0.005), and a
      smaller PASA (mean, 67.1 degrees  +/- 10.4 degrees  compared with 85.2 degrees 
      +/- 6.8 degrees ; p < 0.0001). Within the Down syndrome cohort, the unstable hips
      showed greater femoral anteversion (mean, 32.7 degrees  +/- 14.6 degrees 
      compared with 23.6 degrees  +/- 10.6 degrees ; p = 0.002) and worse global
      acetabular insufficiency compared with the stable hips. No differences between
      the unstable and stable hips were found with respect to acetabular version (mean
      AVC, 7.8 degrees  +/- 5.5 degrees  compared with 7.6 degrees  +/- 3.8 degrees ; p
      = 0.93) and the neck-shaft angle (mean, 133.7 degrees  +/- 6.7 degrees  compared
      with 133.2 degrees  +/- 6.4 degrees ; p = 0.81). CONCLUSIONS: Patients with Down
      syndrome and hip-related symptoms had more retroverted and shallower acetabula
      with globally reduced coverage of the femoral head compared with age and sex
      matched subjects. Hip instability among those with Down syndrome was associated
      with worse global acetabular insufficiency and increased femoral anteversion, but
      not with more severe acetabular retroversion. No difference in the mean femoral
      neck-shaft angle was observed between the stable and unstable hips in the Down
      syndrome cohort. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 29040132
TI  - A Call for Standardization in Platelet-Rich Plasma Preparation Protocols and
      Composition Reporting: A Systematic Review of the Clinical Orthopaedic
      Literature.
AB  - BACKGROUND: Platelet-rich plasma (PRP) is a blood-derived preparation whose use
      has grown exponentially in orthopaedic practice. However, there remains an
      unclear understanding of the biological properties and effects of PRP on
      musculoskeletal healing. Heterogeneous processing methods, unstandardized
      nomenclature, and ambiguous classifications make comparison among studies
      challenging. A comprehensive assessment of orthopaedic clinical PRP trials is key
      to unraveling the biological complexity of PRP, while improving standardized
      communication. Toward this goal, we performed a systematic review of the PRP
      preparation protocols and PRP composition utilized in clinical trials for the
      treatment of musculoskeletal diseases. METHODS: A systematic review of the
      literature was performed from 2006 to 2016. Inclusion criteria were human
      clinical trials, English-language literature, and manuscripts that reported on
      the use of PRP in musculoskeletal/orthopaedic conditions. Basic-science articles,
      editorials, surveys, special topics, letters to the editor, personal
      correspondence, and nonorthopaedic applications (including cosmetic use or dental
      application studies) were excluded. RESULTS: A total of 105 studies (in 104
      articles) met the inclusion criteria for analysis. Of these studies, only 11
      (10%) provided comprehensive reporting that included a clear description of the
      preparation protocol that could be used by subsequent investigators to repeat the
      method. Only 17 studies (16%) provided quantitative metrics on the composition of
      the final PRP product. CONCLUSIONS: Reporting of PRP preparation protocols in
      clinical studies is highly inconsistent, and the majority of studies did not
      provide sufficient information to allow the protocol to be reproduced.
      Furthermore, the current reporting of PRP preparation and composition does not
      enable comparison of the PRP products being delivered to patients. A detailed,
      precise, and stepwise description of the PRP preparation protocol is required to
      allow comparison among studies and provide reproducibility.

PMID- 29040133
TI  - What's New in Shoulder and Elbow Surgery.

PMID- 29040134
TI  - Mortality by Timing of Hip Fracture Surgery: Factors and Relationships at Play.
AB  - In hip fracture care, it is disputed whether mortality worsens when surgery is
      delayed. This knowledge gap matters when hospital managers seek to justify
      resource allocation for prioritizing access to one procedure over another.
      Uncertainty over the surgical timing-death association leads to either surgical
      prioritization without benefit or the underuse of expedited surgery when it could
      save lives. The discrepancy in previous findings results in part from differences
      between patients who happened to undergo surgery at different times. Such
      differences may produce the statistical association between surgical timing and
      death in the absence of a causal relationship. Previous observational studies
      attempted to adjust for structure, process, and patient factors that contribute
      to death, but not for relationships between structure and process factors, or
      between patient and process factors. In this article, we (1) summarize what is
      known about the factors that influence, directly or indirectly, both the timing
      of surgery and the occurrence of death; (2) construct a dependency graph of
      relationships among these factors based explicitly on the existing literature;
      (3) consider factors with a potential to induce covariation of time to surgery
      and the occurrence of death, directly or through the network of relationships,
      thereby explaining a putative surgical timing-death association; and (4) show how
      age, sex, dependent living, fracture type, hospital type, surgery type, and
      calendar period can influence both time to surgery and occurrence of death
      through chains of dependencies. We conclude by discussing how these results can
      inform the allocation of surgical capacity to prevent the avoidable adverse
      consequences of delaying hip fracture surgery.

PMID- 29040135
TI  - Defining Leadership: The Presidential Address to the American Orthopaedic
      Association, San Diego, California, June 11, 2010: AOA Critical Issues.

PMID- 29040136
TI  - Using Clinical Outcomes to Improve Preclinical Testing: Commentary on an article
      by Peter A. Devane, MBChB, MSc, FRACS, et al.: "Highly Cross-Linked Polyethylene
      Reduces Wear and Revision Rates in Total Hip Arthroplasty. A 10-Year Double
      Blinded Randomized Controlled Trial".

PMID- 29040137
TI  - Minimally Invasive THA: Where Are We Now and Where Are We Heading?: Commentary on
      an article by Ciara Stevenson, FRCS, et al.: "Minimal Incision Total Hip
      Arthroplasty. A Concise Follow-up Report on Functional and Radiographic Outcomes
      at 10 Years".

PMID- 29040138
TI  - Vitamin-D Supplementation: A Low-Risk, High-Gain Therapy to Prevent PJI?:
      Commentary on an article by Vishal Hegde, MD, et al.: "Single-Dose, Preoperative
      Vitamin-D Supplementation Decreases Infection in a Mouse Model of Periprosthetic
      Joint Infection".

PMID- 29040139
TI  - CT After ORIF of Acetabular Fractures Detects Residual Displacement Not Seen on
      Radiography and Correlates with Osteoarthritis Risk and THA: Commentary on an
      article by Diederik O. Verbeek, MD, et al.: "Postoperative CT Is Superior for
      Acetabular Fracture Reduction Assessment and Reliably Predicts Hip Survivorship".

PMID- 29040140
TI  - Reply.

PMID- 29040141
TI  - Proof of Concept Study for the Design, Manufacturing, and Testing of a Patient
      Specific Shape Memory Device for Treatment of Unicoronal Craniosynostosis.
AB  - Treatment of unicoronal craniosynostosis is a surgically challenging problem, due
      to the involvement of coronal suture and cranial base, with complex asymmetries
      of the calvarium and orbit. Several techniques for correction have been
      described, including surgical bony remodeling, early strip craniotomy with
      orthotic helmet remodeling and distraction. Current distraction devices provide
      unidirectional forces and have had very limited success. Nitinol is a shape
      memory alloy that can be programmed to the shape of a patient-specific anatomy by
      means of thermal treatment.In this work, a methodology to produce a nitinol
      patient-specific distractor is presented: computer tomography images of a 16
      month-old patient with unicoronal craniosynostosis were processed to create a 3
      dimensional model of his skull and define the ideal shape postsurgery. A mesh was
      produced from a nitinol sheet, formed to the ideal skull shape and heat treated
      to be malleable at room temperature. The mesh was afterward deformed to be
      attached to a rapid prototyped plastic skull, replica of the patient initial
      anatomy. The mesh/skull construct was placed in hot water to activate the mesh
      shape memory property: the deformed plastic skull was computed tomography scanned
      for comparison of its shape with the initial anatomy and with the desired shape,
      showing that the nitinol mesh had been able to distract the plastic skull to a
      shape close to the desired one.The shape-memory properties of nitinol allow for
      the design and production of patient-specific devices able to deliver complex,
      preprogrammable shape changes.

PMID- 29040142
TI  - Proposal of a Budget-Friendly Camera Holder for Endoscopic Ear Surgery.
AB  - Endoscopic ear surgery (EES) is increasingly a preferred technique in otologic
      society. It offers excellent visualization of the anatomical structures directly
      and behind the corners with variable angled telescopes. It also provides reduced
      operative morbidity due to being able to perform surgical interventions with less
      invasive approaches. Operative preparation and setup time and cost of endoscopy
      system are less expensive compared with surgical microscopes. On the other hand,
      the main disadvantage of EES is that the surgery has to be performed with 1
      single hand. It is certainly restrictive for an ear surgeon who has been
      operating with 2 hands under otologic microscopic views for years and certainly
      requires a learning period and perseverance. Holding the endoscope by a second
      surgeon is not executable because of insufficient surgical space.Endoscope/camera
      holders have been developed for those who need the comfort and convenience
      afforded by double-handed microscopic ear surgery. An ideal endoscope holder
      should be easy-to-set up, easily controlled, providing a variety of angled views,
      allowing the surgeon to operate with 2 hands and, budget-friendly. In this
      article, a commercially available 11-inch magic arm camera holder is proposed by
      the authors to be used in EES due to its versatile, convenient, and budget
      friendly features. It allows 2-handed EES through existing technology and is
      affordable for surgeons looking for a low-cost and practical solution.

PMID- 29040143
TI  - Extragingival Pregnancy Pyogenic Granuloma on the Lip.
AB  - Pregnancy pyogenic granuloma is considered a benign common growth that usually
      develops on the gingiva in the second and third trimester of gestation, in
      response to local irritation, trauma or hormonal factors. Here, the authors
      report a case of a primigravida who presented an extragingival pyogenic granuloma
      with a rapid progression in the post-partum. The occurrence on the lower lip in
      the first few days after delivery was a relatively rarity in the present case
      which provoked a meaningful state of anxiety and cancerophobia to the female.
      Complete excision was curative and brought immediate relief of pain and
      discomfort. This clinical report highlights the possibility of pyogenic granuloma
      presenting like a rapid-growing mass on the lip and the importance of clinical
      differential diagnosis of such presentation in this atypical location.

PMID- 29040144
TI  - Surgical Treatment of Dentofacial Deformities Caused by Juvenile Idiopathic
      Arthritis.
AB  - The purpose of our retrospective study was to evaluate the results of
      orthognathic treatment, distraction osteogenesis, and/or prosthetic
      reconstruction of the temporomandibular joints in patients with juvenile
      idiopathic arthritis (JIA).Twelve patients with severely affected
      temporomandibular joints (TMJs) and reduced ramus height were treated with
      mandibular advancement with orthognathic surgery (11) and additional bilateral or
      unilateral mandibular ramus distraction (3) or additional bilateral or unilateral
      prosthetic reconstruction of the TMJ (3). One patient was treated surgically with
      bilateral TMJ prosthetic reconstruction only. The patients were followed up
      clinically and radiologically with emphasis on healing, TMJ function, stability
      of the occlusion, skeletal stability, and facial appearance for an average of 2.3
      years after the final surgery. The mean mandibular advancement was 10.1 mm. The
      mean relapse at pogonion was 2.1 mm, which represents 20.8% of the surgical
      advancement. The occlusion was stable in 11/12 patients. The TMJ function was
      good and the facial esthetics improved in all patients. Orthognathic treatment
      and mandibular ramus distraction osteogenesis provide beneficial lengthening of
      the mandibular body in JIA patients with asymptomatic and stabile condyles. In
      adult patients with relapse of the disease or postoperative condylar relapse
      prosthetic total joint replacement is a reliable and safe alternative.

PMID- 29040145
TI  - Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratio for the Effusion Viscosity in
      Otitis Media.

PMID- 29040146
TI  - The Role of Preoperative Imaging in the Management of Nonsyndromic Lambdoid
      Craniosynostosis.
AB  - BACKGROUND: The necessity of imaging for patients with craniosynostosis is
      controversial. Lambdoid synostosis is known to be associated with additional
      anomalies, but the role of imaging in this setting has not been established. The
      purpose of this study was to evaluate the impact of preoperative imaging on
      intraoperative and postoperative management among patients undergoing operative
      intervention for lambdoid craniosynostosis. METHODS: A retrospective review of
      patients undergoing cranial vault remodeling for lambdoid craniosynostosis
      between January 2006 and 2014 was conducted. Patient demographics, age at
      computed tomography scan, age at surgery, results of the radiologic evaluation,
      operative technique, and modification of the diagnosis following the radiologic
      studies were analyzed. A pediatric neuroradiology and the surgical team
      interpreted the radiographs. The primary outcome was change in intraoperative or
      postoperative management based on imaging results. RESULTS: A total of 11
      patients were diagnosed with lambdoid synostosis. Of these patients, 81.8% had
      abnormalities on imaging relevant to operative planning. The most common
      anomalies were Chiari I malformation (45%) and venous anomalies of the posterior
      fossa (36%). Preoperative imaging altered the management of 9 (81.8%) patients.
      Closer follow-up was required for 6 patients (54%). Suboccipital decompression
      was performed in 4 patients (36%). Venous anomalies were found in 4 patients
      (36%). The diagnosis was changed from positional plagiocephaly to lambdoid
      synostosis in 2 patients (18%). CONCLUSIONS: Given the frequency and significance
      of radiographic abnormalities in the setting of lamboid synostosis, preoperative
      imaging should be considered during the operative planning phase as it can affect
      postoperative and intraoperative management.

PMID- 29040147
TI  - Longitudinal Assessment of Developmental Outcomes in Infants Undergoing Late
      Craniosynostosis Repair.
AB  - Evaluation of infants with craniosynostosis for surgical intervention, as opposed
      to conservative management, remains a challenge within the field of craniofacial
      surgery. Studies have consistently demonstrated that surgical repair of
      craniosynostosis is ideally performed between 3 and 12 months of age. As such,
      there is limited data regarding neurocognitive development in infants who
      initially present with uncorrected craniosynostosis after 12 months of age.
      Moreover, the impact of cranial vault surgery on neurocognitive development at
      all ages remains under investigation. A prospective, nonrandomized study was
      performed. All children with nonsyndromic craniosynostosis who presented for
      initial evaluation after 12 months of age were enrolled. The Bayley Scales of
      Infant and Toddler Development, Third Edition (Bayley-III) was utilized to assess
      pre- and postoperative cognitive development and comparisons were made to
      normative values. Developmental delay is defined as scoring < 85. Five infants,
      average age 26 months (13-43 months) at initial presentation, underwent cranial
      vault remodeling and developmental testing. Fused cranial sutures involved:
      metopic (n = 4), and right coronal (n = 1). Cognitive testing demonstrated that 4
      of 5 infants (80%) were developmentally delayed at presentation (scores: 60, 70,
      72, and 80), and 1 infant was within normal limits (score: 100). Postoperative
      testing was performed between 2 and 12 months postoperatively. Universal
      improvement was observed in infants who were delayed prior to surgery (80, 80,
      75, and 90, respectively). The infant who was not delayed prior to surgery
      remained within normal limits after surgery. This study demonstrates an
      association between cranial vault surgery and cognitive improvement in infants
      presenting late with developmental delay.

PMID- 29040148
TI  - Long-Term Effects of Bone Morphogenetic Protein-2-Loaded Calcium Phosphate on
      Maxillary Sinus Lift Surgery for Delayed and Simultaneous Dental Implantation.
AB  - Maxillary sinus lift surgery (MSLS) is considered to be a useful treatment method
      for patients with atrophic alveolar bone. Choosing a suitable surgical procedure
      to simultaneously decrease graft absorption and obtain long-term survival of
      dental implants is still a challenge. In this study, 20 patients received MSLS
      with graft of bone morphogenetic protein 2 (BMP2)-loaded calcium phosphate.
      Dental implants were placed simultaneously in 10 patients receiving MSLS (1-stage
      group), and in 10 patients receiving dental implants with a 3 to 6 months delay
      (2-stage group). The effects were evaluated based on clinical and radiographic
      examination during a 4 to 5 years follow-up. The results showed that only 1
      perforation of the maxillary sinus mucosa was observed in 1-stage group, and was
      patched with a collagen membrane. An average bone gain of 6.8 mm was observed,
      and all implants exhibited no looseness, peri-implantitis, or fracture, all of
      which were stable during the follow-up and exhibited nice dental function during
      a 4 to 5 years follow-up. The loss of peri-implant bone height was 1.12 +/- 0.47
      and 1.10 +/- 0.39 mm, the probing depth of periodontal pocket was 1.79 +/- 0.62
      and 1.81 +/- 0.71 mm, the sulcular bleeding index was 1.63 +/- 0.47 and 1.72 +/-
      0.54 in 1-stage group and 2-stage group, respectively, and no significant
      differences existed between these 2 groups. These findings implied that BMP2
      loaded calcium phosphate may be a suitable material for MSLS, especially for
      patients with minimal bone height. Clinicians can use the 1- or 2-stage technique
      based on clinical condition, patients' choice and clinicians' experience. In
      patients where implants cannot be stabilized for patients with minimal bone
      height, 2-stage surgery may be more suitable.

PMID- 29040149
TI  - The Pantheon Variant of the Classic Cathedral Dome Procedure for Parieto
      Occipital Skull Deformities.
AB  - OBJECTIVE: To describe a new technique for the reconstruction of parieto
      occipital skull deformities. METHODS AND RESULTS: The technique is a variant of
      the previously described "cathedral dome procedure" used for frontal skull
      deformities. The authors apply the same principle of remodeling by making
      meridional slat craniotomies surrounding the depressed dome of the posterior
      skull deformity, followed by "green-stick fracture-reshaping" of the meridional
      slats to elevate and support the excised depressed dome. The authors present an
      illustrative patient with a follow-up of 2 years and an excellent cosmetic
      result. CONCLUSION: The authors introduce a new operative technique for the
      reconstruction of parieto-occipital skull deformities with excellent long-term
      results. The freshly reconstructed occiput resembles the dome of the pantheon in
      Rome, Italy, whose unique features inspired us to name this procedure the
      "Pantheon" variant of the cathedral dome operation.

PMID- 29040150
TI  - Clinical Evaluation of Standardized Fronto-Orbital Advancement for Correction of
      Isolated Trigonocephaly.
AB  - Corrective surgery of trigonocephaly is a major challenge, owing to the complex
      development of the craniofacial skull. Although reports on the clinical success
      of standardized fronto-orbital advancement have been promising, there is a lack
      of studies, assessing this method. Hence, the aim of our study was to evaluate
      the clinical outcome of a standardized fronto-orbital advancement procedure for
      correction of isolated nonsyndromic trigonocephaly, in our patient cohort. The
      retrospective study included 30 patients from 2008 to 2015. Inclusion criteria
      were treatment-naive children with isolated nonsyndromic trigonocephaly, being
      treated with standardized frontoorbital advancement in our department. We
      considered postoperative complications and the Whitaker Score to evaluate the
      success of the clinical outcome. Surgery was performed at a mean age of 9.3
      months. The mean operation time was 153 minutes. All patients were assigned I
      according to the Whitaker score. One patient suffered from a small
      inconsequential subdural hematoma. Another patient suffered from dural tears,
      which were identified and treated intraoperatively. No major complications
      occurred within our patient cohort. The standardized fronto-orbital advancement
      is a safe and successful method, as it is associated with a high morphological
      outcome and low complication rate.

PMID- 29040151
TI  - Sex Differences in Vascular Reactivity to Angiotensin II During the Evolution of
      Myocardial Infarction.
AB  - The influence of sex on the vascular response during the progression of
      myocardial infarction (MI) has not been extensively studied. In this work, we
      analyzed the differences of the vasoconstriction induced by angiotensin II (Ang
      II) in the absence and presence of valsartan (200 nM) on the aortic rings of male
      and female Wistar rats at 2, 4, 24, and 48 hours and 1, 2, 3, and 4 weeks after
      induction of MI. In the aortic rings of males, an increase was observed in the
      contractile response that lasts up to 4 weeks; on females, this effect is
      diminished since 48 hours until reaching sham group values at 2 weeks of coronary
      occlusion. The incubation of valsartan generated greater reduction on
      vasoconstriction in males than females. In relation to the determination of
      infarct areas, we found them between 30% and 40% in all experimental groups. In
      addition, the index of hypertrophy was determined and no significant changes were
      observed in female rats, while in males we reported an increase at 2, 3, and 4
      weeks. In conclusion, we found differences in vascular reactivity due to sex, as
      well as on the response of Ang II via AT1 during the evolution of MI.

PMID- 29040152
TI  - Acute Laryngeal Dystonia Associated With Asenapine Use: A Case Report.

PMID- 29040153
TI  - Vortioxetine and Aripiprazole Combination in Treatment-Resistant Obsessive
      Compulsive Disorder: A Case Report.

PMID- 29040154
TI  - Clozapine-Associated Neutropenia and Agranulocytosis.

PMID- 29040155
TI  - The complexities of fibromyalgia and its comorbidities.
AB  - PURPOSE OF REVIEW: Fibromyalgia syndrome (FMS) is defined as chronic, widespread
      musculoskeletal pain and tenderness with concomitant mood and cognitive
      dysfunction. Several comorbidities have been reported to be associated with FMS.
      We reviewed the literature concerning the most noteworthy chronic conditions
      associated with FMS. RECENT FINDINGS: There is mounting evidence displaying the
      concurrence of fibromyalgia and coexisting medical and psychiatric conditions.
      Such comorbidities may blur the classical clinical presentations and erroneously
      lead to misinterpretation of disease activity. The recognition of this fact
      should be underlined, as misrecognition may lead to excessive therapy and
      avoidable side-effects of medications on the one hand and to a better handling of
      FMS on the other hand, leading to improved clinical outcomes. SUMMARY: A greater
      proportion of psychiatric and rheumatologic disorders are associated with FMS
      patients than the population. Consequently, physicians treating patients with
      either condition should keep in mind that these patients may have such
      comorbidities and should be treated accordingly.

PMID- 29040156
TI  - Accelerated atheromatosis and arteriosclerosis in primary systemic vasculitides:
      current evidence and future perspectives.
AB  - PURPOSE OF REVIEW: Primary systemic vasculitides (PSV) encompass a subset of
      autoimmune diseases, characterized by inflammation of blood vessels.
      Atheromatosis and arteriosclerosis may be accelerated in several PSV and account
      for the increased rate of cardiovascular morbidity that some exhibit. We aimed to
      summarize recent studies reporting on the acceleration of atheromatosis and/or
      arteriosclerosis in each type of PSV, using state-of-the-art noninvasive vascular
      biomarkers with clinical value as end points. RECENT FINDINGS: Limited number of
      PSV patients and methodology limitations reduce the value of many published
      studies. Accelerated atheromatosis, as measured by the use of carotid
      ultrasonagraphy (plaques and intimal-medial thickening) and increased arterial
      stiffening, as measured by the use of applanation tonometry (carotid to femoral
      pulse wave velocity), are currenly well established in Takayasu arteritis,
      Kawasaki disease and Behcet's disease. The association of atheromatosis and
      arteriosclerosis with polyarteritis nodosa and small vessel vasculitides remains
      less established and studied, so far. SUMMARY: Accelerated atheromatosis and
      arteriosclerosis or arteriosclerosis are established in some PSV. The potential
      clinical value of easy-to-measure and clinically useful noninvasive vascular
      biomarkes prompts the need for large prospective cohorts in order to provide
      useful future guidance regarding the prognosis and treatment of PSV patients.

PMID- 29040157
TI  - Development and use of biochemical markers in osteoarthritis: current update.
AB  - PURPOSE OF REVIEW: There is an increasing demand for noninvasive and descriptive
      biochemical markers (biomarkers) in osteoarthritis; for enabling early drug
      development (including translational research), evaluating clinical trial at an
      early stage and for subtyping. Purpose of the review is to review and comment on
      current availability of such biomarkers. RECENT FINDINGS: Many different
      biomarkers have been tested in the last 18 months. The main focus has been on
      testing whether the biomarkers, whether is reflect joint tissue turnover or
      inflammatory status, can differentiate osteoarthritis patients from healthy
      controls or whether the biomarkers are associated with progression. Less than a
      handful of studies, investigate the role of the biomarkers as response markers.
      Thus, there is still a great need for developing biomarkers that reflect disease
      activity and thereby can be used for treatment response or patient phenotyping.
      SUMMARY: Osteoarthritis is the most common form of joint disease. This presents
      the osteoarthritis research community and pharmaceutical companies developing
      disease-modifying osteoarthritis drugs (DMOADs) with great opportunities. There
      are different osteoarthritis subtypes, which complicates the traditional
      approaches for developing new treatments. If we can identify new markers that can
      distinguish different subtypes, this can greatly facilitate drug development from
      early discovery to late clinical development.

PMID- 29040158
TI  - The Association of Changing Practice Settings on Maintenance of Certification
      Exam Outcomes: A Comparative Study of General Internists Over Time.
AB  - PURPOSE: To investigate how changing to or from solo practice settings relates to
      maintenance of certification (MOC) exam performance. METHOD: The authors
      conducted a retrospective analysis of exam pass/fail outcomes for 7,112
      physicians who successfully completed their initial MOC cycle from 2000 to 2004.
      Initial physician MOC practice characteristics records, demographic information,
      and exam performance were linked with exam pass/fail outcomes from their second
      MOC cycle from 2006 to 2014 (5,215 physicians after attrition). Exam pass/fail
      outcomes for physicians' second MOC cycle were compared among four groups: those
      who remained in group practice across both MOC cycles, those who changed from
      group to solo practice, those who changed from solo to group practice, and those
      who remained in solo practice across both MOC cycles. RESULTS: Physicians who
      changed from solo to group practice performed significantly better than those who
      remained in solo practice (odds ratio [OR] = 1.67; 95% confidence interval [CI] =
      1.11, 2.51; P = .027). Conversely, physicians changing from group to solo
      practice performed significantly worse than physicians staying in group practice
      (OR = 0.60; 95% CI = 0.45, 0.80; P = .002). Meanwhile, physicians who changed
      from solo to group practice performed similarly to physicians remaining in group
      practice (OR = 0.95; 95% CI = 0.67, 1.35; P = 0.76). CONCLUSIONS: Changes in
      solo/group practice status were associated with second-cycle MOC exam
      performance. This study provides evidence that the context in which a physician
      practices may have an impact on their MOC exam performance.

PMID- 29040159
TI  - New Approach for Differentiation of Bone Marrow Mesenchymal Stem Cells Toward
      Chondrocyte Cells With Overexpression of MicroRNA-140.
AB  - Mesenchymal stem cells are widely stimulated by transforming growth factor beta-3
      (TGFbeta3) for chondrocyte differentiation. The objective of our study was to
      establish a new method for differentiation of human mesenchymal stem cells toward
      chondrocyte by overexpression of MicroRNA-140 (miR-140), and also this method was
      compared with method of induction with TGFbeta3 in high-cell density culture
      systems. Mesenchymal stem cells were harvested from bone marrow of human. We
      prepared vectors and then was used for recombinant Lenti virus production in HEK
      293 cell. Transducted cells were cultured in monolayer culture system and were
      harvested after days 7, 14, and 21. Real time polymerase chain reaction (RT-PCR)
      was performed to evaluate the cartilage-specific genes in the mRNA levels. Also,
      in order to confirm our results, we have done immunocytochemistry technique. Bone
      marrow mesenchymal stem cells (BMSCs) were transducted with recombinant Lenti
      virus, and miR-140 was expressed. Immunocytochemical method confirmed the
      differentiation of BMSC toward chondrocyte with handling cartilage matrix genes.
      Also real-time PCR showed that after expression of miR-140 in transducted BMSCs
      significantly increased gene expression of collagen type II and aggrecan and
      downregulated expression of collagen type I when compared with the mRNA levels
      measured in nontransducted BMSCs. These results were compatible compared with
      TGFbeta3 induction method as control positive. In this study, we described a new
      approach and technique that may be applied for differentiation of BMSCs to
      chondrocyte instead of stimulation with TGFbeta3. Our data implies that miR-140
      is a potent chondrogenic differentiation inducer for BMSCs, and we have shown
      increasing chondrogenic differentiation by using miR-140 overexpression.

PMID- 29040160
TI  - ECMO: 40 Years Later.

PMID- 29040161
TI  - Prognostic factor analysis in 325 patients with Graves' disease treated with
      radioiodine therapy.
AB  - INTRODUCTION: I therapy is a choice for Graves' hyperthyroidism. Several factors
      that affect the success of I treatment in Graves' disease (GD) patients have been
      put forward. The aim of this retrospective study was to evaluate the factors
      influencing the success of I therapy and the occurrence of hypothyroidism after I
      therapy. PATIENTS AND METHODS: We reviewed 325 GD patients, who were well
      documented out of 779 cases, treated with I in the First Affiliated Hospital of
      Xi'an Jiaotong University between 2010 and 2016. We collected the potential
      influencing factors, including demographic data (age, sex, family history),
      iodine intake state, antithyroid drugs (ATD) taking, thyroid texture,
      complications of hyperthyroidism, physical and laboratory examinations [thyroid
      weight, effective I half-life time (Teff), 24-h iodine uptake rate, tri
      iodothyronine, thyroxine, free tri-iodothyronine (FT3), free thyroxine, thyroid
      stimulating hormone, thyroglobulin antibody, thyroid microsome antibody,
      thyrotropin receptor antibody], and final administered dosages according to
      Quimby formula. The correlations between the prognosis of GD patients and these
      factors were analyzed by logistic regression analysis. RESULTS: Out of 325
      patients, 247 (76.00%) were treated successfully with radioiodine. GD patients
      who were cured by I therapy were more likely to have smaller thyroid [odds ratio
      (OR)=0.988, 95% confidence interval (CI)=0.980-0.996, P=0.002], lower FT4 levels
      (OR=0.993, 95% CI=0.988-0.997, P=0.002), and shorter time of ATD withdrawal
      before I treatment (OR=0.985, 95% CI=0.975-0.996, P=0.002). Hypothyroidism
      occurred in 132 (41.00%) out of 325 patients. There was an increased risk of
      early hypothyroidism in patients with lower 24-h iodine uptake (OR=0.964, 95%
      CI=0.941-0.988, P=0.004), and treated with a lower total dose of iodine
      (OR=0.892, 95% CI=0.824-0.965, P=0.005) and a higher iodine dose per garm of
      thyroid tissue (OR=5.414E+14, 95% CI=45.495-6.444E+27, P=0.027). CONCLUSION: Our
      results showed that I treatment was more successful in patients with lower weight
      of the thyroid, lower free thyroxine level, and shorter ATD taking period.
      Furthermore, early hypothyroidism after radioiodine treatment was more likely to
      occur in patients with lower 24-h iodine uptake, lower total dose of iodine, and
      higher iodine dose per garm of thyroid tissue.

PMID- 29040164
TI  - Brief Report: CD52 Expression on CD4+ T Cells in HIV-Positive Individuals on
      cART.
AB  - BACKGROUND: HIV persists in a latent state in quiescent CD4 T cells preventing
      eradication of HIV. CD52 is a surface molecule modulated by HIV. We aimed at
      examining factors related to CD52 expression on CD4 T cells in HIV-positive
      individuals and the impact of initiation of combination antiretroviral therapy
      (cART). METHODS: Peripheral blood mononuclear cells from 18 HIV-positive
      individuals and 10 uninfected age- and sex-matched controls were examined by flow
      cytometry for CD38 and CD52 expression on CD4 T cells. Stimulation assays were
      performed on 8 healthy blood donors to determine a cutoff for CD52 expression.
      RESULTS: All examined CD4 T cells expressed CD52. However, both CD4 T cells with
      higher (CD52) and with lower CD52 expression (CD52dim) were found in HIV-positive
      individuals compared to uninfected controls. Two % CD52dim cells defined groups
      of high and low CD52: the group of individuals with high CD52 had higher CD4
      counts at baseline (447 vs. 54 cells/uL, P = 0.02) and higher increase in CD4
      counts during follow-up compared with low CD52 (P = 0.02). After 12 months of
      cART, CD52 increased (median fluorescence intensity 4846 vs. 5621, P < 0.05),
      whereas CD38 decreased (median fluorescence intensity 1519 vs. 730, P < 0.0001).
      CONCLUSIONS: All HIV-positive individuals in this cohort had CD4 T cells that
      expressed CD52. Higher CD4 counts were found in those with high CD52.
      Furthermore, an increase in CD52 was found after 12 months of cART, indicating
      that anti-CD52 antibodies may be more efficient for depletion of CD4 T cells in
      HIV-positive individuals on cART.

PMID- 29040162
TI  - Brief Report: AIDS-Defining Events and Deaths in HIV-Infected Children and
      Adolescents on Antiretrovirals: A 14-Year Study in Thailand.
AB  - BACKGROUND: Data are scarce on the long-term clinical outcomes of perinatally HIV
      infected children and adolescents receiving antiretroviral therapy (ART) in
      low/middle-income countries. We assessed the incidence of mortality before
      (early) and after (late) 6 months of ART and of the composite outcome of
      new/recurrent AIDS-defining event or death >6 months after ART start (late
      AIDS/death) and their associated factors. METHODS: Study population was
      perinatally HIV-infected children (<=18 years) initiating ART within the Program
      for HIV Prevention and Treatment observational cohort (NCT00433030). Factors
      associated with late AIDS/death were assessed using competing risk regression
      models accounting for lost to-follow-up and included baseline and time-updated
      variables. RESULTS: Among 619 children, "early" mortality incidence was 99 deaths
      per 1000 person-years of follow-up [95% confidence interval (CI): 69 to 142] and
      "late" mortality 6 per 1000 person-years of follow-up (95% CI: 4 to 9). Of the
      553 children alive >6 months after ART initiation, median age at ART initiation
      was 6.4 years, CD4% 8.2%, and HIV-RNA load 5.1 log10 copies/mL. Thirty-eight (7%)
      children developed late AIDS/death after median time of 3.3 years: 24 died and 24
      experienced new/recurrent AIDS-defining events (10 subsequently died). Factors
      independently associated with late AIDS/death were current age >=13 years
      (adjusted subdistribution hazard ratio 4.9; 95% CI: 2.4 to 10.1), HIV-RNA load
      always >=400 copies/mL (12.3; 95% CI: 4.0 to 37.6), BMI-z-score always <-2 SD
      (13.7; 95% CI: 3.4 to 55.7), and hemoglobin <8 g/dL at least once (4.6; 95% CI:
      2.0 to 10.5). CONCLUSIONS: After the initial 6 months of ART, being an
      adolescent, persistent viremia, poor nutritional status, and severe anemia were
      associated with poor clinical outcomes. This supports the need for novel
      interventions that target children, particularly adolescents with poor growth and
      uncontrolled viremia.

PMID- 29040163
TI  - Adipose Tissue is Enriched for Activated and Late-Differentiated CD8+ T Cells and
      Shows Distinct CD8+ Receptor Usage, Compared With Blood in HIV-Infected Persons.
AB  - BACKGROUND: Adverse viral and medication effects on adipose tissue contribute to
      the development of metabolic disease in HIV-infected persons, but T cells also
      have a central role modulating local inflammation and adipocyte function. We
      sought to characterize potentially proinflammatory T-cell populations in adipose
      tissue among persons on long-term antiretroviral therapy and assess whether
      adipose tissue CD8 T cells represent an expanded, oligoclonal population.
      METHODS: We recruited 10 HIV-infected, non-diabetic, overweight or obese adults
      on efavirenz, tenofovir, and emtricitabine for >4 years with consistent viral
      suppression. We collected fasting blood and subcutaneous abdominal adipose tissue
      to measure the percentage of CD4 and CD8 T cells expressing activation,
      exhaustion, late differentiation/senescence, and memory surface markers. We
      performed T-cell receptor (TCR) sequencing on sorted CD8 cells. We compared the
      proportion of each T-cell subset and the TCR repertoire diversity, in blood
      versus adipose tissue. RESULTS: Adipose tissue had a higher percentage of CD3CD8
      T cells compared with blood (61.0% vs. 51.7%, P < 0.01) and was enriched for both
      activated CD8HLA-DR T cells (5.5% vs. 0.9%, P < 0.01) and late-differentiated
      CD8CD57 T cells (37.4% vs. 22.7%, P < 0.01). Adipose tissue CD8 T cells displayed
      distinct TCRbeta V and J gene usage, and the Shannon Entropy index, a measure of
      overall TCRbeta repertoire diversity, was lower compared with blood (4.39 vs.
      4.46; P = 0.05). CONCLUSIONS: Adipose tissue is enriched for activated and late
      differentiated CD8 T cells with distinct TCR usage. These cells may contribute to
      tissue inflammation and impaired adipocyte fitness in HIV-infected persons.

PMID- 29040165
TI  - Dating Violence Against HIV-Infected Youth in South Africa: Associations With
      Sexual Risk Behavior, Medication Adherence, and Mental Health.
AB  - BACKGROUND: As perinatal HIV-infected youth become sexually active, the potential
      for onward transmission becomes an increasing concern. In other populations,
      intimate partner violence (IPV) is a risk factor for HIV acquisition. We build on
      this critical work by studying the role of IPV in facilitating onward
      transmission among HIV-infected youth-an important step toward effective
      intervention. SETTING: Soweto, South Africa. METHODS: Self-report surveys were
      completed by 129 perinatal HIV-infected female youth (aged 13-24 years). We
      calculated the IPV prevalence and used logistic models to capture the association
      between IPV and health outcomes known to facilitate onward HIV transmission (eg,
      risky sex, poor medication adherence, depression, and substance abuse). RESULTS:
      A fifth of perinatal HIV-infected participants reported physical and/or sexual
      IPV in the past year; one-third reported lifetime IPV. Childhood adversity was
      common and positively associated with IPV. Past-year physical and/or sexual IPV
      was positively correlated with high-risk sex [odds ratio (OR) = 8.96; 95%
      confidence interval (CI): 2.78 to 28.90], pregnancy (OR = 6.56; 95% CI: 1.91 to
      22.54), poor medication adherence to antiretroviral therapy (OR = 5.37; 95% CI:
      1.37 to 21.08), depression (OR = 4.25; 95% CI: 1.64 to 11.00), and substance
      abuse (OR = 4.11; 95% CI: 1.42 to 11.86). Neither past-year nor lifetime IPV was
      associated with viral load or HIV status disclosure to a partner. CONCLUSIONS: We
      find that IPV may increase risk for onward HIV transmission in perinatal HIV
      infected youth by both increasing engagement in risky sexual behaviors and
      lowering medication adherence. HIV clinics should consider integrating primary
      IPV prevention interventions, instituting routine IPV screening, and collocating
      services for victims of violence.

PMID- 29040166
TI  - Measurement of Retinal Vessels as a Biomarker of Cerebrovascular Aging in Older
      HIV-Positive Men Compared With Controls.
AB  - BACKGROUND: To compare retinal vascular measurements, biomarkers of cerebral
      small vessel disease, in HIV-positive men aged 50 years and older with similarly
      aged HIV-negative men and younger HIV-positive men. METHODS: We recruited white,
      nondiabetic men into a cross-sectional substudy of a larger cohort including 3
      demographically matched groups. Optic disc-centered 45-degree color fundus
      photographs were used to calculate central retinal arterial and venous caliber
      and the arterial-venous ratio (AVR). We used univariate and multivariable linear
      regression to compare retinal vessel measurements in the 3 groups and to identify
      factors associated with AVR. RESULTS: All HIV-positive men were virologically
      suppressed. In a multivariable model, study group was not associated with AVR
      [adjusted beta 0.010 for HIV-positive men <50 (n = 39) compared with HIV-positive
      men aged >=50 years (n = 120), 95% confidence interval [CI] -0.018 to 0.038, P =
      0.47; adjusted beta 0.00002 for HIV-negative men >=50 years (n = 52), 95% CI 
      0.022 to 0.022, P = 0.99]. Factors associated with lower AVR were systolic blood
      pressure (adjusted beta -0.009 per +10 mm Hg, 95% CI -0.015 to -0.003, P =
      0.002), history of stroke or transient ischemic attack (adjusted beta -0.070, 95%
      CI -0.12 to -0.015, P = 0.01), and recent recreational drug use (adjusted beta 
      0.037, 95% CI -0.057 to -0.018, P = 0.0002). CONCLUSIONS: There were no
      differences in retinal vascular indices between HIV-positive men aged >=50 years
      and HIV-negative men aged >=50 years or HIV-positive men aged <50 years,
      suggesting that HIV is not associated with an increased burden of cerebral small
      vessel disease.

PMID- 29040167
TI  - Country of Birth of Children With Diagnosed HIV Infection in the United States,
      2008-2014.
AB  - BACKGROUND: Diagnoses of HIV infection among children in the United States have
      been declining; however, a notable percentage of diagnoses are among those born
      outside the United States. The impact of foreign birth among children with
      diagnosed infections has not been examined in the United States. METHODS: Using
      the Centers for Disease Control and Prevention National HIV Surveillance System,
      we analyzed data for children aged <13 years with diagnosed HIV infection
      ("children") in the United States (reported from 50 states and the District of
      Columbia) during 2008-2014, by place of birth and selected characteristics.
      RESULTS: There were 1516 children [726 US born (47.9%) and 676 foreign born
      (44.6%)]. US-born children accounted for 70.0% in 2008, declining to 32.3% in
      2013, and 40.9% in 2014. Foreign-born children have exceeded US-born children in
      number since 2011. Age at diagnosis was younger for US-born than foreign-born
      children (0-18 months: 72.6% vs. 9.8%; 5-12 years: 16.9% vs. 60.3%). HIV
      diagnoses in mothers of US-born children were made more often before pregnancy
      (49.7% vs. 21.4%), or during pregnancy (16.6% vs. 13.9%), and less often after
      birth (23.7% vs. 41%). Custodians of US-born children were more often biological
      parents (71.9% vs. 43.2%) and less likely to be foster or nonrelated adoptive
      parents (10.4% vs. 55.1%). Of 676 foreign-born children with known place of
      birth, 65.5% were born in sub-Saharan Africa and 14.3% in Eastern Europe. The top
      countries of birth were Ethiopia, Ukraine, Uganda, Haiti, and Russia.
      CONCLUSIONS: The increasing number of foreign-born children with diagnosed HIV
      infection in the United States requires specific considerations for care and
      treatment.

PMID- 29040170
TI  - Kidney Transplantation and the Impact on Health-Related Quality of Life in Frail
      Patients.

PMID- 29040168
TI  - Failure of Isoflurane Cardiac Preconditioning in Obese Type 2 Diabetic Mice
      Involves Aberrant Regulation of MicroRNA-21, Endothelial Nitric-oxide Synthase,
      and Mitochondrial Complex I.
AB  - BACKGROUND: Diabetes impairs the cardioprotective effect of volatile anesthetics,
      yet the mechanisms are still murky. We examined the regulatory effect of
      isoflurane on microRNA-21, endothelial nitric-oxide synthase, and mitochondrial
      respiratory complex I in type 2 diabetic mice. METHODS: Myocardial
      ischemia/reperfusion injury was produced in obese type 2 diabetic (db/db) and
      C57BL/6 control mice ex vivo in the presence or absence of isoflurane
      administered before ischemia. Cardiac microRNA-21 was quantified by real-time
      quantitative reverse transcriptional-polymerase chain reaction. The dimers and
      monomers of endothelial nitric-oxide synthase were measured by Western blot
      analysis. Mitochondrial nicotinamide adenine dinucleotide fluorescence was
      determined in Langendorff-perfused hearts. RESULTS: Body weight and fasting blood
      glucose were greater in db/db than C57BL/6 mice. Isoflurane decreased left
      ventricular end-diastolic pressure from 35 +/- 8 mmHg in control to 23 +/- 9 mmHg
      (P = 0.019, n = 8 mice/group, mean +/- SD) and elevated +/-dP/dt 2 h after post
      ischemic reperfusion in C57BL/6 mice. These beneficial effects of isoflurane were
      lost in db/db mice. Isoflurane elevated microRNA-21 and the ratio of endothelial
      nitric-oxide synthase dimers/monomers and decreased mitochondrial nicotinamide
      adenine dinucleotide levels 5 min after ischemia in C57BL/6 but not db/db mice.
      MicroRNA-21 knockout blocked these favorable effects of isoflurane, whereas
      endothelial nitric-oxide synthase knockout had no effect on the expression of
      microRNA-21 but blocked the inhibitory effect of isoflurane preconditioning on
      nicotinamide adenine dinucleotide. CONCLUSIONS: Failure of isoflurane cardiac
      preconditioning in obese type 2 diabetic db/db mice is associated with aberrant
      regulation of microRNA-21, endothelial nitric-oxide synthase, and mitochondrial
      respiratory complex I.

PMID- 29040171
TI  - Biomechanical Comparison of Single-Bundle and Double-Bundle Posterior Cruciate
      Ligament Reconstruction: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Of the many issues regarding surgical techniques for posterior
      cruciate ligament (PCL) reconstruction, the choice between single-bundle (SB) and
      double-bundle (DB) reconstruction is one of the most debated. However, it is
      unclear which of the reconstruction techniques yields better outcomes in knees
      with a PCL injury. The purpose of this meta-analysis was to compare the benefits
      of SB and DB PCL reconstruction in terms of biomechanical outcomes. METHODS: The
      MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of
      Science, and SCOPUS electronic databases were searched for relevant articles
      comparing the outcomes of SB and DB PCL reconstruction that were published up
      until August 2016. Data searching, extraction, analysis, and quality assessment
      were performed on the basis of the Cochrane Collaboration guidelines.
      Biomechanical outcomes of both techniques were evaluated using various outcomes.
      Results involving continuous outcomes are presented as standardized mean
      differences (SMDs) with 95% confidence intervals (CIs). RESULTS: Ten
      biomechanical studies were included. There were no significant biomechanical
      differences between the groups with respect to external rotation, varus rotation,
      or coupled external rotation of the tibia with posterior drawer force at any knee
      flexion angle. However, posterior laxity measured using the posterior drawer test
      showed significantly better results after DB compared with SB reconstruction at
      low flexion (SMD = -0.90, 95% CI = -1.24 to -0.56, I = 0%), 30 degrees  (SMD = 
      0.79, 95% CI = -1.28 to -0.31, I = 48%), 60 degrees  (SMD = -0.87, 95% CI = -1.33
      to -0.40, I = 33%), and 90 degrees  (SMD = -0.73, 95% CI = -1.11 to -0.35, I =
      27%). CONCLUSIONS: Anatomic DB reconstruction of the PCL is superior to anatomic
      SB reconstruction in terms of restoration of anteroposterior stability. However,
      it remains unclear which technique yields better improvement in terms of external
      rotation laxity, varus laxity, and coupled external rotation of the tibia with
      posterior drawer force. High-quality randomized controlled trials are required to
      confirm and expand on these results.

PMID- 29040173
TI  - Family caregivers.

PMID- 29040174
TI  - Reversal agents for oral anticoagulants.

PMID- 29040172
TI  - Cartilage Restoration of the Patellofemoral Joint.

PMID- 29040175
TI  - Adult asthma: Diagnosis and treatment.

PMID- 29040176
TI  - HPV awareness and vaccination rates in college-aged male athletes.
AB  - College-aged males are at high risk for human papillomavirus (HPV); however,
      vaccination rates remain low, suggesting minimal HPV knowledge. Therefore, an
      educational intervention was developed and implemented to determine if an
      increase in HPV knowledge, perceived HPV risk, intention and perceived self
      efficacy to obtain the vaccine, and vaccination rates were observed.

PMID- 29040177
TI  - Providing self-management education to patients with type 2 diabetes mellitus:
      Addressing basic nutrition and hypoglycemia.
AB  - NPs and other primary care providers will continue to encounter a growing
      population of patients with type 2 diabetes mellitus. Helping patients engage in
      self-care behaviors is essential to achieve blood glucose control and prevent
      diabetes-related complications. This article explores opportunities to provide
      education to patients with diabetes mellitus on the important self-care topics of
      nutrition and hypoglycemia during a primary care visit.

PMID- 29040178
TI  - Understanding employment contracts: What to know before you sign.
AB  - NPs are conscientious providers, but when it comes to their own careers, they may
      not be as careful to apply the same prevention strategies, monitoring, and
      hypervigilance that they use with their patients to avoid poor outcomes. This
      article identifies potential risks in employment contracts and offers suggestions
      for avoiding disputes.

PMID- 29040179
TI  - Finding joy in the workplace: We all have a role to play.

PMID- 29040180
TI  - Terminating a patient from care.

PMID- 29040182
TI  - Variable clinical presentations of babesiosis: A case series.
AB  - Human babesiosis continues to spread in multiple regions of the United States. It
      is transmitted by Ixodes species ticks, as are Lyme disease and anaplasmosis. Its
      variable clinical presentations, together with serologic detection limitations,
      require that a high index of clinical suspicion be present for prompt diagnosis.
      This article discusses case presentations showing the wide range of symptoms and
      presentations that are possible with babesiosis.

PMID- 29040183
TI  - The Prognostic Impact of the Pathological Response to Neoadjuvant Dose-Dense
      Therapy for Ovarian Carcinoma.
AB  - OBJECTIVE: The aim of this study was to assess the use of the pathological
      response to neoadjuvant chemotherapy (NAC) for predicting disease prognosis in
      patients with advanced ovarian cancer who received neoadjuvant dose-dense weekly
      paclitaxel and carboplatin (dd-TC) therapy. METHODS: We retrospectively
      investigated patients with advanced epithelial ovarian, tubal, or peritoneal
      carcinoma treated at our hospital from July 2004 to October 2014. Patients
      received dd-TC therapy as NAC followed by interval debulking surgery (IDS).
      Specimens resected during IDS were divided into 4 groups based on pathological
      response: grade 1, most tumor cells appeared to be viable; grade 2a, most tumor
      cells had disappeared, whereas the remaining tumor cells were vacuolated or
      degenerated; grade 2b, small numbers of viable tumor cells were observed; and
      grade 3, small aggregations of macrophages were seen. RESULTS: Sixty-eight
      patients were enrolled. The median number of NAC cycles was 3 (range, 2-6), and
      51 patients (75.0%) achieved complete resection at IDS. Regarding pathological
      response, 7 (10.3%) patients were classified as grade 1, 11 (16.2%) as grade 2a,
      46 (67.7%) as grade 2b, and 4 (5.9%) as grade 3. In univariate and multivariate
      analyses, grades 2b and 3 pathological responses were significant favorable
      prognostic factors for progression-free survival (P = 0.028; hazard ratio, 0.48;
      95% confidence interval, 0.26-0.92). CONCLUSIONS: Although the pathological
      complete response rate to NAC was low in this study, both complete and good
      pathological responses to NAC might be favorable prognostic factors for PFS in
      patients with advanced ovarian cancer who receive dd-TC.

PMID- 29040184
TI  - Proceedings From the 1st International Conference 'Current Concepts and
      Controversies in Gynecologic and Urologic Oncology'.
AB  - The N.N. Alexandrov National Cancer Center of Belarus organized a collaborative
      international conference entitled 'Current Concepts and Controversies in
      Gynecologic and Urologic Oncology' with the International Gynecologic Cancer
      Society and the United States National Cancer Institute. International, regional,
      and national experts presented recent developments and local conditions in the
      treatment of gynecologic cancers. Findings were reviewed with the intent of
      optimizing the management of women with gynecologic cancers across the
      Commonwealth of Independent States region. At the end of the conference, a
      resolution was adopted to identify areas for improvement and future
      collaborations.

PMID- 29040185
TI  - Sarcopenia Is an Important Prognostic Factor in Patients With Cervical Cancer
      Undergoing Concurrent Chemoradiotherapy.
AB  - OBJECTIVE: This study aimed to investigate the correlation of sarcopenia findings
      with prognostic factors in patients with cervical cancer (CC) undergoing
      concurrent chemoradiotherapy (CCRT). METHODS: We retrospectively collected data
      on body composition and clinicopathological features from the medical records of
      60 patients with CC who underwent CCRT and analyzed correlations between
      prognosis and changes in body composition as measured by computed tomography
      (skeletal muscle and iliopsoas muscle [IM]). Statistical analyses were performed
      using the Mann-Whitney U test. Progression-free survival (PFS) and overall
      survival (OS) were analyzed using the Kaplan-Meier method. Cox proportional
      hazard regression was used for univariate and multivariate analyses. RESULTS: The
      median follow-up for all patients who were alive at the last follow-up was 33.5
      months (range, 1-104 months). The PFS and OS rates were worse for patients with
      at least 15.0% than for those with less than 15.0% loss of skeletal muscle and IM
      from baseline (P < 0.001 for both). Furthermore, multivariate analyses showed
      that at least 15.0% loss of IM was an independent prognostic factor for PFS and
      OS (P = 0.002 for both). CONCLUSIONS: Sarcopenia (>=15.0% loss of IM from
      baseline) was revealed to be an important prognostic factor in patients with CC
      undergoing CCRT.

PMID- 29040186
TI  - The Effect of Adenomyosis in Myometrial Invasion and Overall Survival in
      Endometrial Cancer.
AB  - AIM: The aim of this study was to evaluate whether adenomyosis had an effect on
      myometrial tumor invasion, stage of the disease, and survival in endometrial
      cancer. METHODS: Endometrial cancer patients encountered between 2007 and 2016
      were identified from pathology records. Patients who underwent suboptimal
      surgical or medical treatment or with insufficient clinical or surgical data were
      excluded. Patients diagnosed as having concurrent adenomyosis constituted the
      study group. Control group patients were randomly selected in a paired design
      according to the tumor grades in the study group, and for each tumor grade, 4
      times as many as patients were included. Tumor stage, histologic type and grade,
      myometrial invasion, lymphovascular space invasion, presence and location of the
      adenomyosis in myometrial wall, distance from endometrial line, tumor in
      adenomyosis, adjuvant treatment, and relapse were primary outcomes.Age, body mass
      index, medical comorbidities, and type of operation were also recorded.
      Univariate and multivariate Cox proportional hazards regression models were
      performed for overall survival. RESULTS: Of those 1242 endometrial cancer
      patients, 80 with concurrent adenomyosis were identified and compared with 320
      patients without adenomyosis following a paired selection based on tumor grade.
      Higher rates of myometrial invasion, lymphovascular space invasion, tumor
      diameter, and adjuvant treatments were found in the nonadenomyosis group compared
      with adenomyosis group (P <= 0.001). In patients with adenomyosis, rates of early
      stage disease and overall survival were significantly higher compared with the
      control group (P = 0.001 and 0.01, respectively). CONCLUSIONS: Our results showed
      that adenomyosis is significantly associated with lower stage in endometrial
      cancer that may suggest a possible limiting effect on endometrial cancer spread.
      In addition, despite similar rates in disease-free survival and endometrial
      cancer-related death, overall survival rate was significantly higher in the
      presence of adenomyosis and might be considered as a good prognostic factor for
      endometrial cancer.

PMID- 29040187
TI  - Palliative Radiation Therapy for Recurrent Ovarian Cancer: Efficacy and
      Predictors of Clinical Response.
AB  - OBJECTIVE: This study aimed to report response rates and predictors of response
      to palliative radiotherapy (RT) for recurrent ovarian cancer. METHODS/MATERIALS:
      Database review identified 64 patients with symptomatic ovarian cancer recurrence
      who received a total of 76 courses of RT for 103 indications from March 2003 to
      August 2014. Radiotherapy indications were pain (44%), bleeding (32%),
      obstruction (15%), and other (9%). Responses were categorized as complete,
      partial, or none; all response (AR) was the sum of complete and partial
      responses. Response rates were compared using a chi test. Multivariate analysis
      was performed using logistic regression. Patients were followed up for symptom
      recurrence and death. RESULTS: Response rates were significantly higher for pain
      (AR, 87%) and bleeding (93%) than for obstruction (62%) and other (60%; P <
      0.01). Patients treated for pain at nonbony sites had higher response rates (AR
      96%) compared with those treated at bony sites (75%; P = 0.04). Patients with
      clear cell histology had the lowest response rates (AR, 60%) compared with those
      with serous (82%), endometrioid (95%), or other Mullerian histology (85%; P =
      0.01). Platinum status at diagnosis or the time of RT was not associated with
      response, nor was tumor size or number of prior chemotherapy regimens. On
      multivariate analysis, histology, RT indication, and RT dose were independent
      predictors of response (all P < 0.01). CONCLUSIONS: Palliative RT provides relief
      of pain and bleeding in most patients with ovarian cancer recurrence. Patients
      with symptomatic obstruction, bony involvement, and clear cell histology may
      experience lower clinical response rates.

PMID- 29040188
TI  - Phagocytosis of Extracellular Vesicles Extruded From the Placenta by Ovarian
      Cancer Cells Inhibits Growth of the Cancer Cells.
AB  - OBJECTIVE: Ovarian cancer is a common gynecological cancer, and parity is
      negatively associated with the incidence of this disease. This negative
      association is hypothesized to be due in part to shifting the balance of estrogen
      and progesterone toward more progesterone and reduced ovulation during pregnancy.
      However, studies suggested that parity is also associated with estrogen
      independent gynecological cancers suggesting balance of hormones may not be the
      only protective factor. Extracellular vesicles (EVs) play an important role in
      cell-to-cell communication in physiological and pathological conditions. During
      pregnancy, large amounts of EVs are extruded from the placenta, and they seem to
      be involved in the remarkable adaptation of a woman's body to normal pregnancy.
      We hypothesized that EVs extruded from the placenta play a role in this
      protective effect. METHODS: Placental EVs were collected from first-trimester
      placentae, and cancer cell EVs were isolated from ovarian cancer cells. The EVs
      were exposed to ovarian cancer cells for 48 hours. The proliferation of cancer
      cells and the cell cycle were measured. In addition, phagocytosis of deported
      placental EVs by cancer cells was also measured. RESULTS: The proliferation of
      cancer cells was significantly reduced by treatment with placental EVs (P =
      0.001, analysis of variance), but not EVs from monocytes (P = 0.195), compared
      with untreated cancer cells. Furthermore, placental EVs also prevented the
      proliferation of cancer cells induced by cancer cell-derived EVs (P = 0.001).
      This inhibition of proliferation of ovarian cancer cells was partially due to
      phagocytosis of placental EVs by cancer cells. Phagocytosis of placental EVs
      delayed progression through the cell cycle. Calreticulin, a phagocytic "eat me"
      signal carried by placental EVs significantly inhibited ovarian cancer growth (P
      = 0.001). CONCLUSIONS: Our data demonstrated that EVs extruded from the placenta
      prevented ovarian cancer cell growth by a mechanism that involved delaying
      progression of the cell cycle after phagocytosis of the EVs.

PMID- 29040189
TI  - The Patient and Observer Scar Assessment Scale to Evaluate the Cosmetic Outcomes
      of the Robotic Single-Site Hysterectomy in Endometrial Cancer.
AB  - OBJECTIVE: The objective of this study was to evaluate the cosmetic outcome of
      robotic single-site hysterectomy (RSSH) in early-stage endometrial cancer.
      METHODS: We prospectively collected patient demographics, operative times,
      complications, pathologic results, and length of stay on all patients who
      underwent RSSH for early-stage endometrial cancer. The Patient and Observer Scar
      Assessment Scale (POSAS) was used for the evaluation of the cosmetic outcome.
      RESULTS: Forty-five patients were included in our study from January 2012 to
      October 2015. The median age of patients was 63 years (range, 35-84 years), and
      the median body mass index was 26.5 kg/m (range, 18-39 kg/m). No
      laparoscopic/laparotomic conversion was registered. The median docking time,
      console time, and total operative time were 7 minutes (range, 4-14 minutes), 46
      minutes (range, 20-100 minutes), and 90 minutes (range, 45-150 minutes),
      respectively. The median blood loss was 50 mL (range, 10-150 mL). Nine patients
      underwent pelvic lymphadenectomy, and the median number of pelvic lymph nodes was
      13 (range, 10-32). The median time to discharge was 3 days (range, 2-6 days). No
      intraoperative complications occurred, whereas we did observe 1 early
      postoperative complication. The oncological outcome was directly comparable to
      the literature. Patients reported low pain scores and high satisfaction in terms
      of postoperative scarring. The POSAS scores confirmed excellent cosmetic outcome
      of RSSH. CONCLUSION: Robotic single-site hysterectomy provided an efficient
      option for gynecologic oncologic surgery. The POSAS revealed high objective and
      patient-evaluated outcome, and patients were highly satisfied with the overall
      outcome of the appearance of their scars.

PMID- 29040190
TI  - Novel Therapeutics for Ovarian Cancer: The 11th Biennial Rivkin Center Ovarian
      Cancer Research Symposium.
AB  - OBJECTIVE: The aim of this study was to summarize developments in novel
      therapeutics for ovarian cancer presented at the Ovarian Cancer Research
      Symposium held at the University of Washington. METHODS: A symposium of the
      leaders in ovarian cancer research was convened to present and discuss current
      advances and future directions in ovarian cancer research. RESULTS: The fourth
      session was held on September 13, 2016, and focused on Novel Therapeutics for
      Ovarian Cancer. The session featured a keynote presentation on Novel
      Immunotherapeutics for Ovarian Cancer from Nora Disis and an invited oral
      presentation from Scott Kaufmann that discussed poly (ADP-ribose) polymerase
      (PARP) Inhibitor Combinations for the Treatment of Ovarian Cancer. Eight
      additional oral presentations were selected from abstract submissions. Thirty
      eight abstracts were presented as posters highlighting recent advances in tumor
      immunology, PARP inhibition, chemoresistance, and novel targets for ovarian
      cancer therapy. CONCLUSIONS: PARP inhibitors, immunotherapies, and targeted
      therapies are but some of the expanding number of treatment options for ovarian
      cancer patients. Identification of the subsets of patients who will benefit most
      from these treatments remains the subject of intense preclinical and clinical
      research. Evidence presented at this symposium suggests that non-BRCA patients
      also benefit from PARP inhibitor therapies. Improved understanding of the
      mechanisms of chemoresistance and encouraging preclinical data presented for
      combinatorial approaches may soon yield new therapies for ovarian cancers that
      are resistant and refractory to standard treatments.

PMID- 29040191
TI  - Incidence Patterns and Survival of Gynecological Sarcoma in Germany: Analysis of
      Population-Based Cancer Registry Data on 1066 Women.
AB  - OBJECTIVE: Sarcomas of the female genital tract are rare tumors. They are
      described to be associated with a poor prognosis when compared with gynecogical
      carcinoma. The aim of this study was to report incidence patterns and survival
      rates for gynecological sarcoma (GS) in Germany. METHODS/MATERIALS: Clinical data
      and survival rates for patients with GS diagnosed in Germany between 2009 and
      2013 were extracted from the German national center for population-based cancer
      registry data. Incidence patterns and 5-year relative survival rates were
      calculated. RESULTS: A total of 1066 GSs were included in our analysis during a 5
      year time span. The uterus was the most common site, with 87.9% of all cases. The
      annual age-standardized incidence rate (old European standard) was 8.7 per 1
      million women for all GSs. The median age at diagnosis was 59 years. The
      prognosis ranged according to site, stage, and subtype, for example, from a 5
      year relative survival of 53.0% (uterine leiomyosarcoma) if confined to the
      pelvis, to a very good 5-year relative survival of 97.2% (endometrial stromal
      sarcoma). CONCLUSIONS: Despite the rareness of GS, the size of the data set
      allows for a differentiation of subtypes according to morphology and site of
      origin. Clinically relevant differences in incidence and prognosis between
      subgroups were observed.

PMID- 29040192
TI  - 2017 American Pancreatic Association Presidential Address: Revitalizing
      Pancreatitis Research.

PMID- 29040194
TI  - Fatty Pancreas: Should We Be Concerned?
AB  - The metabolic consequences of visceral fat deposition are well known, and the
      presence of intrapancreatic fat (IPF) has been recognized for decades. However,
      our knowledge about the distribution of fat in the pancreas and its clinical
      implications is in a nascent stage. Various terms have been proposed to describe
      IPF; for the purpose of this narrative review, we chose the general term fatty
      pancreas. Herein, we describe the radiologic, endoscopic, and histopathologic
      aspects of diagnosing fatty pancreas and provide an overview of the diseases
      associated with this condition. Our purpose is to highlight diagnostic challenges
      and identify specific clinical questions that would benefit from further study.
      As evident in this review, IPF is associated with various metabolic diseases,
      pancreatitis, pancreatic cancer, and precancer-yet establishing causality needs
      careful, further study.

PMID- 29040195
TI  - Grade Assignment by Ki-67 Proliferative Index, Mitotic Count, and Phosphohistone
      H3 Count in Surgically Resected Gastrointestinal and Pancreatic Neuroendocrine
      Tumors.
AB  - OBJECTIVES: The aim of this study was to evaluate the concordance in grade
      assignment for gastroenteropancreatic neuroendocrine tumors using mitotic count
      (MC), Ki-67 proliferative index (KPI), and phosphohistone H3 count (PHH3C).
      METHODS: Resected gastroenteropancreatic neuroendocrine tumors were graded based
      on MC, KPI, and PHH3C. Concordance was determined using a weighted kappa
      statistic. Median survival across each grade category was determined using Kaplan
      Meier methods. RESULTS: Of the 110 patients, the majority had gastrointestinal
      primaries and grade 1 or 2 tumors. Rates of discordance in grade assignment were
      29% of cases for KPI versus MC (kappaW = 0.26), 32% for PHH3C versus MC (kappaW =
      0.34), and 32% for PHH3C versus KPI (kappaW = 0.37). There was fair agreement
      between grading by KPI and MC. Relative to grade by KPI and MC, PHH3C tended to
      upgrade tumors. The proportion alive at 3 and 5 years was not significantly
      different for patients with grade 1 versus grade 2 tumors. CONCLUSIONS: The
      concordance between KPI and MC was fair. Phosphohistone H3 count tended to
      upgrade tumors using the cutoffs established by MC. Grade 1 and grade 2 tumors
      were associated with similar survival regardless of grading method. The overall
      relevance of the current cutoff values used in grading neuroendocrine tumors may
      need to be revisited.

PMID- 29040196
TI  - Carcinoid Syndrome Complicating a Pancreatic Neuroendocrine Tumor: A Case Report.
AB  - Neuroendocrine tumors (NETs) comprise a heterogeneous group of neoplasms. These
      tumors can produce a wide variety of hormones that can lead to syndromes of
      hormone excess, such as carcinoid syndrome. We present the case of a 47-year-old
      man who presented with right upper quadrant abdominal pain and emesis. He was
      found to have metastatic pancreatic NET and was treated with systemic
      chemotherapy. He subsequently developed dyspnea on exertion and was found to have
      severe right-sided heart disease secondary to elevated levels of serum serotonin.
      He was successfully treated with surgical tricuspid and pulmonic valve
      replacement. True carcinoid syndrome with pancreatic NETs is rare, but, as a
      treatable complication of the disease, is an important entity for which
      oncologists should be familiar.

PMID- 29040198
TI  - Pancreatitis in Patients With Pancreas Divisum.

PMID- 29040199
TI  - In Vitro Effect of Lysozyme on Albumin Deposition to Hydrogel Contact Lens
      Materials.
AB  - SIGNIFICANCE: Albumin deposition on contact lenses could be detrimental to
      contact lens (CL) wear because this may increase the risk of bacterial binding
      and reduce comfort. Lysozyme deposition on selected lens materials would reduce
      albumin deposition on lenses. PURPOSE: This study aims to determine if lysozyme
      deposition on CLs could act as a barrier against subsequent albumin adsorption,
      using an in vitro model. METHODS: Six hydrogel CL materials (etafilcon A,
      polymacon, nelfilcon A, omafilcon A, ocufilcon B, and nesofilcon A) were
      evaluated. Four CLs of each type were soaked in lysozyme solution for 16 hours at
      37 degrees C. Lysozyme-coated lenses were then placed in vials with 1.5 mL of
      artificial tear solution containing I-labeled albumin for 16 hours at 37 degrees
      C with shaking. Four uncoated lenses of each type were used as controls. Lenses
      soaked in radiolabeled albumin were rinsed in a phosphate-buffered saline
      solution, and radioactive counts were measured directly on lenses using a gamma
      counter. Albumin uptake on lenses was measured using a calibration curve by
      plotting radioactive counts versus protein concentration. RESULTS: Results are
      reported as mean +/- SD. Lysozyme-coated etafilcon A lenses exhibited lower
      levels of deposited albumin than uncoated etafilcon A lenses (58 +/- 12 vs. 84 +/
      5 ng/lens; P < .05). There were no differences in albumin adsorption between
      control (uncoated) and lysozyme-coated polymacon (105 +/- 10 vs. 110 +/- 34
      ng/lens), nelfilcon A (51 +/- 7 vs. 42 +/- 20 ng/lens), omafilcon A (90 +/- 20
      vs. 80 +/- 38 ng/lens), ocufilcon B (87 +/- 20 vs. 115 +/- 50 ng/lens), and
      nesofilcon A (170 +/- 29 vs. 161 +/- 10 ng/lens) lens materials (P > .05).
      Uncoated nesofilcon A lenses deposited the highest amount of albumin when
      compared with other uncoated lenses (P < .05). CONCLUSIONS: This study
      demonstrates that lysozyme deposited onto etafilcon A resists the deposition of
      albumin, which may potentially be beneficial to CL wearers.

PMID- 29040200
TI  - Geospatial mapping can be used to identify geographic areas and social factors
      associated with intentional injury as targets for prevention efforts distinct to
      a given community.
AB  - BACKGROUND: Geographic information systems (GIS) have proven effective in
      studying intentional injury in various communities; however, GIS is not
      implemented widely for use by Level I trauma centers in understanding patient
      populations. Our study of intentional injury combines the capabilities of GIS
      with a Level I trauma center registry to determine the spatial distribution of
      victims and correlated socioeconomic factors. METHODS: One thousand ninety-nine
      of 3,109 total incidents of intentional trauma in the trauma registry from 2005
      to 2015 had sufficient street address information to be mapped in GIS. Comparison
      of these data, coupled with demographic data at the block group level, determined
      if any clustering or spatial patterns existed. Geographic information systems
      delivered these comparisons using several spatial statistics including kernel
      density, ordinary least squares test, and Moran's index. RESULTS: Kernel density
      analysis identified four major areas with significant clustering of incidents.
      The Moran's I value was 0.0318. Clustering exhibited a positive z-score and
      significant p value (p < 0.01). Examination of socioeconomic factors by spatial
      correlation with the distribution of intentional injury incidents identified
      three significant factors: unemployment, single-parent households, and lack of a
      high school degree. Tested factors did not exhibit substantial redundancy
      (variance inflation factor < 7.5). Nonsignificant tested factors included race,
      proximity to liquor stores and bars, median household income, per capita income,
      rate with public assistance, and population density. CONCLUSION: Spatial
      representation of trauma registry data using GIS effectively identifies high-risk
      areas for intentional injury. Analysis of local socioeconomic data identifies
      factors unique to those high-risk areas in the observed community. Implications
      of this study may include the routine use of GIS by Level I trauma centers in
      assessing intentional injury in a given community, the use of that data to guide
      the development of trauma prevention, and the assessment of other mechanisms of
      trauma using GIS. LEVEL OF EVIDENCE: Epidemiological, level IV.

PMID- 29040201
TI  - Don't call me crazy! Delirium occurs outside of the intensive care unit.
AB  - INTRODUCTION: Delirium has been well studied among patients in the intensive care
      unit (ICU); however, data beyond the ICU is limited. The purpose of this study is
      to prospectively evaluate the incidence and associated risk factors for delirium
      in noncritical care areas (NCCA). METHODS: After institutional review board
      approval, a prospective cohort study was conducted at our urban Level I Trauma
      Center from December 2015 to February 2016. All patients admitted to the
      designated study area by a trauma surgeon were included. The Confusion Assessment
      Method (CAM) was administered every 12 hours until discharge. Delirious patients
      (CAM+) were administered the CAM-S to quantify the severity of delirium.
      Demographics, laboratory data, and inpatient medication lists were analyzed.
      RESULTS: Of 148 participants, 12 (8%) were CAM+ and 136 (92%) were CAM-. The
      average CAM-S of CAM+ patients was 7 +/- 3. Included patients were aged 52 +/- 20
      years and 45% were men. Of patients 65 years or older, 9 (21%) were CAM+.
      Medications associated with delirium were: albuterol (p = 0.01), atorvastatin (p
      = 0.01), duloxetine (p = 0.04), sertraline (p = 0.04), folic acid (p = 0.01),
      thiamine (p = 0.01), vitamin D (p < 0.001), haloperidol (p = 0.04), metoprolol (p
      = 0.02), and vancomycin (p = 0.02). Abnormal laboratory values associated with
      delirium included: Albumin (p = 0.03; odds ratio [OR], 7.94, 95% confidence
      interval [CI], 1.1-63.20), Calcium (p = 0.01; OR, 4.95; 95% CI, 1.5-16.7), Sodium
      (p = 0.04; OR, 3.91; 95% CI, 1.13-13.5), hematocrit (p = 0.04), and mean
      corpuscular hemoglobin concentration (p < 0.05; OR, 5.29; 95% CI, 1.19-23.46).
      CONCLUSIONS: Our study demonstrated an 8% incidence of delirium overall in NCCA,
      increasing to 21% in patients 65 years or older. Many risk factors identified
      among NCCA patients are consistent with the ICU literature; however, our CAM+
      patients had additional risk factors which have not been previously associated
      with the development of delirium. Screening of NCCA patients for delirium should
      be considered. LEVEL OF EVIDENCE: Prognostic and Epidemological, level IV.

PMID- 29040202
TI  - Re-examination of a Battlefield Trauma Golden Hour Policy.
AB  - BACKGROUND: Most combat casualties who die, do so in the prehospital setting.
      Efforts directed toward alleviating prehospital combat trauma death, known as
      killed in action (KIA) mortality, have the greatest opportunity for eliminating
      preventable death. METHODS: 4,542 military casualties injured in Afghanistan from
      September 11, 2001 to March 31, 2014 were included in this retrospective analysis
      to evaluate proposed explanations for observed KIA reduction following a mandate
      by Secretary of Defense Robert M. Gates that transport of injured service members
      occur within 60 minutes. Using inverse probability weighting to account for
      selection bias, data were analyzed using multivariable logistic regression and
      simulation analysis to estimate the effects of 1) gradual improvement, 2) damage
      control resuscitation, 3) harm from inadequate resources, 4) change in wound
      pattern, and 5) transport time on KIA mortality. RESULTS: The effect of gradual
      improvement measured as a time trend was not significant (AOR=0.99; 95%CI 0.94
      1.03; p=0.58). For casualties with military injury severity score >= 25, the odds
      of KIA mortality were 83% lower for casualties who needed and received
      prehospital blood transfusion (AOR=0.17; 95%CI 0.06-0.51; p=0.002); 33% lower for
      casualties receiving initial treatment by forward surgical teams (AOR=0.67; 95%CI
      0.58-0.78; p<0.001); 70%, 74%, and 87% lower for casualties with dominant
      injuries to head (AOR=0.30; 95%CI 0.23-0.38; p<0.001), abdomen (AOR=0.26, 95%CI
      0.19-0.36; p<0.001) and extremities (AOR=0.13; 95%CI 0.09-0.17; p<0.001); 35%
      lower for casualties categorized with blunt injuries (AOR=0.65; 95%CI 0.46-0.92;
      p=0.01); and 39% lower for casualties transported within one hour (AOR=0.61;
      95%CI 0.51-0.74; p<0.001). Results of simulations in which transport times had
      not changed after the mandate indicate that KIA mortality would have been 1.4%
      higher than observed, equating to 135 more KIA deaths (95%CI 105-164).
      CONCLUSIONS: Reduction in KIA mortality is associated with early treatment
      capabilities, blunt mechanism, select body locations of injury, and rapid
      transport. LEVEL OF EVIDENCE: Retrospective/Case-control, Level III.

PMID- 29040203
TI  - The temporal response and mechanism of action of tranexamic acid in endothelial
      glycocalyx degradation.
AB  - BACKGROUND: The endothelial glycocalyx (GCX) plays an important role in vascular
      barrier function. Damage to the GCX occurs due to a variety of causes including
      hypoxia, ischemia-reperfusion, stress-related sympathoadrenal activation, and
      inflammation. Tranexamic acid (TXA) may prevent GCX degradation. The therapeutic
      window for TXA administration and the mechanism of action has been under review.
      Membrane-anchored proteases (sheddases) are key components in endothelial cell
      biology including the regulation of vascular permeability. The effect of TXA
      administration on stress-related GCX damage, and the role of sheddases in this
      process was studied in a cell-based model. METHODS: Confluent human umbilical
      vein endothelial cells (HUVEC) were exposed to hydrogen peroxide and/or
      epinephrine (EPI) to stimulate postshock reperfusion. TXA was added at various
      times after hydrogen peroxide (H2O2) and/or EPI exposure. GCX degradation was
      indexed by syndecan-1 and hyaluronic acid release. Activation of endothelial
      sheddases was indexed by A Disintegrin and Metalloproteinase-17 and matrix
      metalloproteinase-9 activity in culture supernatants. RESULTS: Exposure of HUVEC
      to either/both EPI and H2O2 resulted in a cellular stress and GCX disruption
      demonstrated by increased levels of syndecan-1 shedding, hyaluronic acid release,
      tumor necrosis factor-alpha release. Shedding of these GCX components was
      associated with increased activity of both A Disintegrin and Metalloproteinase-17
      and matrix metalloproteinase. Disruption of the GCX was further demonstrated via
      fluorescent imaging, which demonstrated disruption after exposure to either/both
      H2O2 and EPI. Early administration of either TXA or doxycycline resulted in
      preservation of the GCX. Late administration of TXA had no effect, whereas
      doxycycline had some residual protective effect. CONCLUSION: Tranexamic acid as a
      serine protease inhibitor prevented GCX degradation via inhibition of endothelial
      sheddase activation. This effect was not apparent when TXA was administered
      greater than 60 minutes after "simulated" reperfusion. Our study supports the
      clinical practice of early TXA administration in the severely injured patient.

PMID- 29040204
TI  - Perioperative glycemic control and postoperative complications in patients
      undergoing emergency general surgery: What is the role of Plasma Hemoglobin A1c?
AB  - BACKGROUND: Plasma hemoglobin A1c (HbA1c) reflects quality of glucose control in
      diabetic patients. Literature reports that patients undergoing surgery with an
      elevated HbA1c level are associated with increased postoperative morbidity and
      mortality. The aim of our study was to evaluate the impact of HbA1c level on
      outcomes after emergency general surgery (EGS). METHODS: We performed a 3-year
      analysis of our prospectively maintained EGS database. Patients who had HbA1c
      levels measured within 3 months before surgery were included. Patients were
      divided into two groups (HbA1c < 6 and HbA1c >= 6). Our primary outcome measures
      included in-hospital complications (major and minor complications), hospital and
      intensive care unit length of stay, and mortality. Secondary outcomes measures
      were 30-day complications, readmissions, and mortality. Multivariate and linear
      regressions were performed. RESULTS: Of the 402 study patients, mean age was 61
      +/- 12 years, 53% were females, and 63.8% were diabetics. Overall, 49% had an
      HbA1c >= 6%; the mortality rate was 6%. Those with hypertension, history of
      coronary artery disease, and body mass index of 30 kg/m or greater were more
      likely to have HbA1c of 6.0% or greater. 7.9% patients experienced major
      complications. Patients with HbA1c of 6% or greater had a higher complication
      rate (36% vs 11%, p < 0.001) than those with HbA1c less than 6%. However there
      was no difference in mortality between two groups (p = 0.09). After controlling
      for confounders, HbA1c >= 6.0% (odds ratio [OR], 2.9; p < 0.01) and a
      postoperative random blood sugar (RBS) of 200 mg/dL or greater (OR, 2.3; p <
      0.01) were independent predictors of major complications. Patients with both
      HbA1c of 6.0% or greater and postoperative RBS of 200 or greater had higher odds
      (OR, 4.2; p < 0.01) of developing major complication. After adjusting for
      confounders, a higher HbA1c was independently correlated with a higher
      postoperative RBS (b = 0.494, [19.7-28.4], p = 0.02), but there was no
      correlation with the preoperative RBS. CONCLUSION: Patients with HbA1c of 6.0% or
      greater and a postoperative RBS of 200 mg/dL or greater have a four times higher
      risk of developing major complications after EGS. A preoperative HbA1c can
      stratify patients prone to develop postoperative hyperglycemia, regardless of
      their preoperative RBS. LEVEL OF EVIDENCE: Prognostic, level III.

PMID- 29040205
TI  - Spleen-preserving distal pancreatectomy in trauma.
AB  - BACKGROUND: Traumatic injuries to the distal pancreas are infrequent. Universally
      accepted recommendations about the need for routine splenectomy with distal
      pancreatectomy do not exist. The aims of this study were to compare outcomes
      after distal pancreatectomy and splenectomy versus spleen-preserving distal
      pancreatectomy, and to define the appropriate patient population for splenic
      preservation. METHODS: All patients who underwent distal pancreatectomy (January
      1, 2007, to December 31, 2014) were identified from the National Trauma Data
      Bank. Patients with concomitant splenic injury and those who underwent partial
      splenectomy were excluded. Demographics, clinical data, procedures, and outcomes
      were collected. Study groups were defined by surgical procedure: distal
      pancreatectomy and splenectomy versus spleen-preserving distal pancreatectomy.
      Baseline characteristics between groups were compared with univariate analysis.
      Multivariate analysis was performed with logistic and linear regression to
      examine differences in outcomes. RESULTS: Over the 8-year study period, 2,223
      patients underwent distal pancreatectomy. After excluding 1,381 patients with
      concomitant splenic injury (62%) and 8 (<1%) who underwent partial splenectomy,
      834 (38%) remained for analysis. Median age was 23 years (range, 0-86 years) and
      634 (77%) were male. Mechanism of injury was penetrating in 413 (50%) patients.
      Of the 834 patients, 469 (56%) underwent splenectomy and 365 (44%) patients did
      not. Compared with patients who underwent distal pancreatectomy and splenectomy,
      those who underwent spleen-preserving distal pancreatectomy were younger (p <
      0.001), more likely to have sustained blunt trauma (p < 0.001), and had a lower
      Injury Severity Score (p < 0.001). On multivariate analysis, only hospital length
      of stay (LOS) was significantly shorter among patients undergoing spleen
      preserving distal pancreatectomy (p = 0.017). Complications, mortality, and
      intensive care unit LOS were not significantly different. CONCLUSION: In young
      patients after blunt trauma who are not severely injured, a spleen-preserving
      distal pancreatectomy should be considered to allow for conservation of splenic
      function and a shorter hospital LOS. In all other patients, the surgeon should
      not hesitate to remove the spleen with the distal pancreas. LEVEL OF EVIDENCE:
      Therapy, level IV.

PMID- 29040206
TI  - The life-saving effect of "adenosine, lidocaine, and magnesium" cocktail during
      hypovolemic shock: One stone, three birds?

PMID- 29040207
TI  - Trauma pneumonectomy for major thoracic bleeding: When should we consider about
      it?

PMID- 29040208
TI  - An update on gain-of-function mutations in primary immunodeficiency diseases.
AB  - PURPOSE OF REVIEW: Most primary immunodeficiencies described since 1952 were
      associated with loss-of-function defects. With the advent and popularization of
      unbiased next-generation sequencing diagnostic approaches followed by functional
      validation techniques, many gain-of-function mutations leading to
      immunodeficiency have also been identified. This review highlights the updates on
      pathophysiology mechanisms and new therapeutic approaches involving primary
      immunodeficiencies because of gain-of-function mutations. RECENT FINDINGS: The
      more recent developments related to gain-of-function primary immunodeficiencies
      mostly involving increased infection susceptibility but also immune dysregulation
      and autoimmunity, were reviewed. Updates regarding pathophysiology mechanisms,
      different mutation types, clinical features, laboratory markers, current and
      potential new treatments on patients with caspase recruitment domain family
      member 11, signal transducer and activator of transcription 1, signal transducer
      and activator of transcription 3, phosphatidylinositol-4,5-biphosphate 3-kinase
      catalytic 110, phosphatidylinositol-4,5-biphosphate 3-kinase regulatory subunit
      1, chemokine C-X-C motif receptor 4, sterile alpha motif domain containing 9
      like, and nuclear factor kappa-B subunit 2 gain-of-function mutations are
      reviewed for each disease. SUMMARY: With the identification of gain-of-function
      mutations as a cause of immunodeficiency, new genetic pathophysiology mechanisms
      unveiled and new-targeted therapeutic approaches can be explored as potential
      rescue treatments for these diseases.

PMID- 29040209
TI  - Inherited and acquired clinical phenotypes associated with neuroendocrine tumors.
AB  - PURPOSE OF REVIEW: Overview of neuroendocrine neoplasms in the context of their
      associations with primary and secondary immunodeficiency states. RECENT FINDINGS:
      Malignancies of neuroendocrine origin are well known to be associated with
      hereditary syndromes, including multiple endocrine neoplasia type 1, von Hippel
      Lindau syndrome, neurofibromatosis type 1, and tuberous sclerosis. This review
      includes the X-linked form of hyper-IgM syndrome (XHIGM), due to mutations in the
      CD40Ligand gene (CD40LG), as an additional inherited disorder with susceptibility
      to such malignancies, and discusses neuroendocrine tumors (NETs) arising in other
      immunocompromised states. Of all primary immune deficiency diseases, NETs appear
      to be unique to XHIGM patients. Outcomes for XHIGM patients with NETs is poor,
      and the mechanism behind this association remains unclear. In secondary immune
      deficiency states, NET occurrences were primarily in patients with HIV or AIDS,
      the autoimmune disease systemic lupus erythematosus and solid organ transplant
      recipients. Gastroenteropancreatic NETs were most frequent in XHIGM patients,
      whereas nongastroenteropancreatic-NETs, like Merkel cell carcinoma and small-cell
      lung carcinoma, affected HIV/AIDS patients. Possible mechanisms as to the nature
      of these associations are discussed, including chronic infections and
      inflammation, and CD40-CD40L interactions. Many questions remain, and further
      studies are needed to clarify the predisposition of patients with XHIGM to the
      development of NETs. Given that many of these patients present late in their
      disease state and have poor outcomes, it is imperative to keep a high index of
      suspicion at the advent of early signs and symptoms. Regular monitoring with
      laboratory or imaging studies, including tumor markers, may be warranted, for
      which further studies are needed. SUMMARY: Of all primary immunodeficiency
      diseases, NETs appear to be unique to XHIGM, and the mechanism behind this
      association remains unclear. Outcome for XHIGM patients with NETs is poor, and it
      is imperative to keep a high index of suspicion at the advent of early signs and
      symptoms.

PMID- 29040210
TI  - Anticholinergics for asthma: a long history.
AB  - PURPOSE OF REVIEW: To provide a fast overview about the introduction and
      development of anticholinergic drugs in Western medicine to their current
      indications particularly in asthma. RECENT FINDINGS: Although short-acting
      muscarinic antagonists have been positioned in the last 15 years for the
      treatment of adults and children with moderate-to-severe acute asthma in the
      emergency setting (reducing the risk of hospital admissions and improving lung
      function), a growing body of evidence has recently emerged that positions the
      long-acting muscarinic anticholinergic tiotropium bromide as add-on therapy to at
      least inhaled corticosteroids (ICS) maintenance therapy in adults, adolescents,
      and children with symptomatic asthma. Thus, the addition of tiotropium bromide to
      ICS alone or ICS and another controller was associated with significant
      improvements in spirometric measures and asthma control, and a significantly
      decrease in the rate of asthma exacerbations. SUMMARY: Short-acting muscarinic
      antagonists and tiotropium bromide have a well established role in the treatment
      of different phases of asthma. Further data are needed to provide more evidence
      on other selective long-acting muscarinic antagonists in addition to tiotropium
      as potential treatment options.

PMID- 29040211
TI  - Altered Macular Microvasculature in Mild Cognitive Impairment and Alzheimer
      Disease.
AB  - BACKGROUND: The goal of the present study was to analyze the macular microvacular
      network in mild cognitive impirment (MCI) and Alzheimer disease (AD). METHODS:
      Twelve patients with AD and 19 patients with MCI were recruited together with 21
      cognitively normal controls with a similar range of ages. Optical coherence
      tomography angiography was used to image the retinal microvascular network at the
      macular region, including retinal vascular network (RVN), superficial vascular
      plexus (SVP), and deep vascular plexus (DVP). Fractal analysis (box counting,
      Dbox) representing the microvascular density was performed in different annular
      zones and quadrantal sectors. The macular ganglion cell-inner plexiform layer (GC
      IPL) thickness was measured using Zeiss OCT. The relationship between the retinal
      microvasculature and clinical manifestations was analyzed. RESULTS: Patients with
      AD had lower densities of RVN, SVP, and DVP in the annulus, from 0.6 to 2.5 mm in
      diameter (P < 0.05) in comparison with controls. Patients with MCI had lower
      density of DVP in the superior nasal quadrant (P < 0.05) than that of the
      controls. There were no significant differences of GC-IPL thickness among groups
      (P > 0.05). There was a trend of vascular density loss from control to MCI then
      AD (P < 0.05). Retinal microvascular density of DVP was correlated with GC-IPL
      thickness (P < 0.05) in patients with AD, but not in patients with MCI and
      controls. CONCLUSIONS: Patients with AD had less density of retinal microvascular
      networks than controls. Our findings suggest the presence of retinal
      microvascular dysfunction in AD.

PMID- 29040212
TI  - Vasopressor Cumulative Dose Requirement and Risk of Early Death During Septic
      Shock: An Analysis From The EPISS Cohort.
AB  - Septic shock is the primary cause of death in intensive care units, with about
      20% of patients dying in the first 3 days. To design future trials focused on
      early mortality, we require knowledge of early indicators that can detect
      patients at high risk of early death from refractory septic shock. The aim of
      this study was to assess whether the cumulative dose of vasopressors (CDV),
      calculated as the cumulative dose of epinephrine + norepinephrine, is a predictor
      of early death (within 72 h) attributable to refractory septic shock (EDASS).
      This substudy of the EPISS trial was based on 370 patients admitted to a French
      ICU for septic shock between 2009 and 2011. The area under the receiving
      operating characteristic curve was calculated for the CDV at 6, 12, 24, 36, and
      48 h after vasopressor initiation, and a strategy to predict the risk of EDASS
      was built based on selected times and thresholds. Among the 370 patients
      included, 51 (14%) died within the first 72 h with 40 (11%) EDASS. A strategy in
      two steps (CDV >= 800 MUg/kg at 6 h and/or CDV >= 2,600 MUg/kg at 24 h) was able
      to predict EDASS with sensitivity of 45%, specificity 97%, positive predictive
      value 78% and negative predictive value 94%. Overall, our results confirm that
      early death directly attributable to septic shock could be effectively predicted
      by the CDV in the first hours of treatment. These results will help to select
      patients eligible for innovative therapies aimed at improving early mortality in
      septic shock.

PMID- 29040213
TI  - Importance of the Complement Alternative Pathway in Serum Chemotactic Activity
      During Sepsis.
AB  - Serum chemotactic activity is important in regulating neutrophil migration. The
      ability of neutrophils to migrate to infectious site is crucial for host
      effective pathogen control, but unregulated neutrophil activation can also cause
      tissue damage. During bacterial sepsis, the complement alternative pathway (AP)
      is massively activated in blood and tissues and reportedly contributes to sepsis
      pathogenesis. Complement factor B (FB) is an essential component of the AP
      activation. However, the impact of FB/AP activation on blood chemotactic activity
      during bacterial infection is unclear. In this study, we found that sera of
      septic mice following cecal ligation and puncture (CLP) had much higher
      chemotactic activities on neutrophils than those of sham animals. Compared with
      wild-type (WT) mice, FB mice had significantly attenuated serum chemotactic
      activity, under both nonseptic and septic conditions. Moreover, sera with the
      activated AP by zymosan and cobra venom factor (CVF) in vitro induced a
      significant increase in neutrophil migration compared with sera without the AP
      activation. Complement activation generates complement cleavage fragment such as
      Ba, C3a, and C5a. To delineate the contribution of these downstream effectors, we
      incubated AP-active sera (AP activated by zymosan/CVF) or sera from sham and
      septic mice with anti-C5a or mAb1379 (anti-Ba) neutralizing antibody. We found
      that anti-C5a, but not mAb1379, markedly attenuated the neutrophil chemotactic
      effect of the AP-activated sera and that of septic sera. Taking together, these
      data suggest that the complement AP activation during bacterial sepsis plays a
      pivotal role in promoting blood chemotactic activity through a C5a-dependent
      mechanism.

PMID- 29040214
TI  - Untreated Relative Hypotension Measured as Perfusion Pressure Deficit During
      Management of Shock and New-Onset Acute Kidney Injury-A Literature Review.
AB  - Maintaining an optimal blood pressure (BP) during shock is a fundamental tenet of
      critical care. Optimal BP targets may be different for different patients. In
      current practice, too often, uniform BP targets are pursued which may result in
      inadvertently accepting a degree of untreated relative hypotension, i.e., the
      deficit between patients' usual premorbid basal BP and the achieved BP, during
      vasopressor support. Relative hypotension is a common but an under-recognized and
      an under-treated sign among patients with potential shock state. From a
      physiological perspective, any relative reduction in the net perfusion pressure
      across an organ (e.g., renal) vasculature has a potential to overwhelm
      autoregulatory mechanisms, which are already under stress during shock. Such
      perfusion pressure deficit may consequently impact organs' ability to function or
      recover from an injured state. This review discusses such pathophysiologic
      mechanisms in detail with a particular focus on the risk of new-onset acute
      kidney injury (AKI). To review current literature, databases of Medline, Embase,
      and Google scholar were searched to retrieve articles that either adjusted BP
      targets based on patients' premorbid BP levels or considered relative hypotension
      as an exposure endpoint and assessed its association with clinical outcomes among
      acutely ill patients. There were no randomized controlled trials. Only seven
      studies could be identified and these were reviewed in detail. These studies
      indicated a significant association between the degree of relative hypotension
      that was inadvertently accepted in real-world practice and new-onset organ
      dysfunction or subsequent AKI. However, this is not a high-quality evidence.
      Therefore, well-designed randomized controlled trials are needed to evaluate
      whether adoption of individualized BP targets, which are initially guided by
      patient's premorbid basal BP and then tailored according to clinical response, is
      superior to conventional BP targets for vasopressor therapy, particularly among
      patients with vasodilatory shock states.

PMID- 29040215
TI  - Role of Receptor for Advanced Glycation End Products in Regulating Lung Fluid
      Balance in Lipopolysaccharide-induced Acute Lung Injury and Infection-Related
      Acute Respiratory Distress Syndrome.
AB  - Receptor for advanced glycation end products (RAGE) is implicated in inflammatory
      responses in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS),
      but its role in pulmonary edema formation remains unclear, especially in
      infection-related ARDS mainly caused by pneumonia or sepsis. In this study, we
      investigated the role of RAGE in alveolar fluid regulation by using RAGE gene
      knockout (RAGE) mice in a murine ALI model induced by lipopolysaccharide (LPS),
      and by comparing soluble RAGE (sRAGE) levels in serum and bronchial alveolar
      lavage fluid between ARDS patients and control subjects. We found that RAGE
      knockout significantly improved alveolar fluid clearance and reduced pulmonary
      vascular albumin leakage upon LPS challenge. Furthermore, LPS-induced substantial
      decrease in lung expression of sodium-potassium ATPase (Na,K-ATPase), epithelial
      sodium channel, and zonula occluden-1 (ZO-1) were fully or partially restored by
      the deletion of RAGE. In addition to this, LPS-induced lung leukocyte
      infiltration and inflammatory cytokine and chemokine release were all attenuated
      in RAGE mice as compared to wide-type mice. In infection-related ARDS patients,
      both serum and bronchial alveolar lavage fluid levels of the sRAGE were much
      higher than those in control subjects, and they were positively correlated with
      pulmonary vascular permeability and levels of interleukin (IL)-6, IL-8, and
      macrophage inflammatory protein (MIP)-2. Taken together, we provided the first
      direct evidence for the essential role of RAGE in regulating lung fluid balance
      in infection-related ARDS/ALI. The underlying mechanisms may involve the
      downregulation of both ion-channel and tight junction proteins mediated by RAGE
      signaling in bacterial endotoxin-induced lung injury.

PMID- 29040217
TI  - Shining the light on genitourinary syndrome of menopause in survivors of breast
      cancer.

PMID- 29040216
TI  - Depressive symptoms screening in postmenopausal women with symptomatic pelvic
      organ prolapse.
AB  - OBJECTIVE: This study aimed to investigate the prevalence of depressive symptoms
      in postmenopausal women with symptomatic pelvic organ prolapse (POP) and to
      identify the factors associated with depressive symptoms in this population.
      METHODS: We conducted a cross-sectional study involving postmenopausal women with
      symptomatic POP who visited the Center of Obstetrics and Gynecology, Peking Union
      Medical College Hospital, Beijing, between July 2016 and March 2017. We collected
      data pertaining to participants' sociodemographic characteristics and medical
      histories. The participants enrolled in the study were evaluated by POP
      quantification (POP-Q), the Pelvic Floor Distress Inventory-20 (PFDI-20), and the
      Pelvic Floor Impact Questionnaire-7 (PFIQ-7), and the severity of their
      depressive symptoms was assessed by the Patient Health Questionnaire-9
      (participants with scores >=10 were considered "positive" for depressive
      symptoms, whereas participants with scores <10 were considered "negative" for
      depressive symptoms). We performed independent-sample t tests, Mann-Whitney U
      test, chi-square tests, Fisher's exact test, and logistic regression to analyze
      our data. RESULTS: In all, 177 participants completed the entire study and were
      thus included in the analysis. Overall, 32.8% of participants were found to have
      depressive symptoms. We noted no differences in sociodemographic characteristics
      or POP-Q stage between participants with and without depressive symptoms (P >
      0.05). However, depressive symptoms were associated with higher PFIQ-7 and PFDI
      20 subscale scores (P < 0.001). PFIQ-7 subscale Urinary Impact Questionnaire
      (UIQ)-7 (odds ratio [OR] 1.038, 95% confidence interval [CI] 1.010-1.066, P =
      0.008), PFDI-20 subscale UDI-6 (OR 1.025, 95% CI 1.007-1.044, P = 0.008), and
      Colorectal-Anal Distress Inventory-8 (OR 1.025, 95% CI 1.005-1.046, P = 0.016),
      which represented the impact on quality of life from lower urinary tract
      symptoms, the distress caused by lower urinary tract symptom and bowel
      dysfunction, respectively, were the risk factors that were independently
      associated with depressive symptoms after multiple logistic regression analysis.
      CONCLUSIONS: Depressive symptoms were present in approximately one-third of
      postmenopausal women with symptomatic POP. Depressive symptoms are not associated
      with POP stage, but are associated with the lower urinary tract symptom and bowel
      dysfunction scores attributable to prolapse. Clinicians should be mindful of
      whether patients with symptomatic POP have depressive symptoms and should address
      POP and any concomitant depressive symptoms as early as possible.

PMID- 29040218
TI  - Perimenopausal depression and early menopause: cause or consequence?

PMID- 29040219
TI  - Effect of 2 years of endurance and high-impact training on preventing
      osteoporosis in postmenopausal women: randomized clinical trial.
AB  - OBJECTIVE: The aim of the study was to analyze the effects of endurance and high
      impact training oriented toward preventing osteoporosis in postmenopausal women
      with calcium and vitamin D supplementation. METHODS: This study was a randomized
      clinical trial. Thirty-six postmenopausal women were randomized to the control
      and experimental groups. Thirty-four women completed the 2-year interventions.
      The control group training involved walking at an intense pace. The experimental
      group conducted high-impact training specifically oriented to prevent
      osteoporosis. Dual-energy x-ray absorptiometry was used to estimate the T-scores
      of the lumbar spine and femoral neck. RESULTS: The fast-walking group showed
      constant T-scores in the femoral neck and improved T-scores in the lumbar spine.
      High-impact exercises produced improvements in both anatomical levels.
      Significant differences were found in the femoral neck (DeltaControl = -0.04,
      DeltaExperimental = 0.28). The differences were not significant in the lumbar
      spine (DeltaControl = 0.27, DeltaExperimental = 0.47). Cohen's effect size (d =
      0.52) suggested a medium practical significance of the trial. The power was 51%.
      CONCLUSIONS: Calcium plus vitamin D supplementation combined with specifically
      oriented exercises had a higher impact in the femoral neck than walking at an
      intense pace. As there were no differences at the lumbar spine level, the results
      were, however, inconclusive concerning which type of exercise was the most
      convenient. Importantly, the fact that the T-scores did not decrease after 2
      years supports the belief that both proposed interventions can be conveniently
      used to prevent osteoporosis in postmenopausal women. A trial with a larger
      sample size would provide consistency to the findings and is warranted given the
      possible effects and benefits.

PMID- 29040220
TI  - Vaginal estrogen in the treatment of genitourinary syndrome of menopause and risk
      of endometrial cancer: an assessment of recent studies provides reassurance.

PMID- 29040221
TI  - Thermoeffector Responses at a Fixed Rate of Heat Production in Heart Failure
      Patients.
AB  - PURPOSE: Heart failure (HF) patients seem to exhibit altered thermoregulatory
      responses during exercise in the heat. However, the extent to which these
      responses are altered due to physiological impairments independently of
      biophysical factors associated with differences in metabolic heat production
      (Hprod), evaporative heat balance requirements (Ereq), and/or body size is
      presently unclear. Therefore, we examined thermoregulatory responses in 10 HF
      patients and 10 age-matched controls (CON) similar in body size during exercise
      at a fixed rate of Hprod and therefore Ereq in a 30 degrees C environment.
      METHODS: Rectal temperature, local sweat rate, and cutaneous vascular conductance
      were measured throughout 60 min of cycle ergometry. Whole-body sweat rate was
      estimated from pre-post nude body weight corrected for fluid intake. RESULTS:
      Despite exercising at the same rate of Hprod (HF, 338 +/- 43 W; CON, 323 +/- 31
      W; P = 0.25), the rise in rectal temperature was greater (P < 0.01) in HF (0.81
      degrees C +/- 0.16 degrees C) than in CON (0.49 degrees C +/- 0.27 degrees C). In
      keeping with a similar Ereq (HF, 285 +/- 40 W; CON, 274 +/- 28 W; P = 0.35), no
      differences in whole-body sweat rate (HF, 0.45 +/- 0.11 L.h; CON, 0.41 +/- 0.07
      L.h; P = 0.38) or local sweat rate (HF, 0.96 +/- 0.17 mg.cm.min; CON, 0.79 +/-
      0.15 mg.cm.min; P = 0.50) were observed between groups. However, the rise in
      cutaneous vascular conductance was lower in HF than in CON (HF, 0.83 +/- 0.42
      au.mm Hg; CON, 2.10 +/- 0.79 au.mm Hg; P < 0.01). In addition, the cumulative
      body heat storage estimated from partitional calorimetry was similar between
      groups (HF, 154 +/- 106 kJ; CON, 196 +/- 174 kJ; P = 0.44). CONCLUSIONS:
      Collectively, these findings demonstrate that HF patients exhibit a blunted skin
      blood flow response, but no differences in sweating. Given that HF patients had
      similar body heat storage to that of CON at the same Hprod, their greater rise in
      core temperature can be attributed to a less uniform internal distribution of
      heat between the body core and periphery.

PMID- 29040222
TI  - Neurovascular Response during Exercise and Mental Stress in Anabolic Steroid
      Users.
AB  - PURPOSE: Increased resting muscle sympathetic nerve activity (MSNA) and lower
      forearm blood flow (FBF) were observed in young men who use anabolic androgenic
      steroids (AAS). However, the response of MSNA and FBF in AAS users triggered by
      muscle mechanoreflex and central command has never been tested. In addition, we
      evaluated the blood pressure (BP) and heart rate (HR) responses during these
      maneuvers. METHODS: Nineteen AAS users (AASU) 31 +/- 6 yr of age and 18 AAS
      nonusers (AASNU) 29 +/- 4 yr of age were recruited. All participants were
      involved in strength training. AAS use was determined using a urine test (liquid
      chromatography with tandem mass spectrometry). MSNA was measured using the
      microneurography technique. FBF was measured by using venous occlusion
      plethysmography. BP was measured using an automatic oscillometric device. HR was
      recorded continuously through ECG. Isometric handgrip exercise was performed at
      30% of the maximal voluntary contraction for 3 min, and mental stress was
      elicited by the Stroop color-word test for 4 min. RESULTS: The MSNA and FBF
      responses during exercise were similar between AASU and AASNU, with a trend
      toward higher MSNA (bursts per minute; P = 0.084) and lower forearm vascular
      conductance (FVC; units; P = 0.084) in AASU than in AASNU. During mental stress,
      AASU showed a significantly higher MSNA (P < 0.05) and lower FBF (P < 0.05)
      compared with AASNU. During both maneuvers, HR and BP increased linearly in both
      groups; however, AASU showed a significantly higher HR compared with AASNU.
      CONCLUSIONS: During muscle mechanoreflex activation (isometric exercise), AASU
      have normal MSNA and FBF responses, whereas during central command (mental
      stress) stimulation, AASU have exacerbated MSNA and blunted vasodilation.
      Therefore, mental stress seems to exacerbate neurovascular control throughout
      stress reaction situations in AASU.

PMID- 29040223
TI  - Effect of Losartan on the Acute Response of Human Elderly Skeletal Muscle to
      Exercise.
AB  - PURPOSE: To investigate the effect of blocking the angiotensin II Type I receptor
      (AT1R) upon the response to acute heavy-resistance exercise in elderly human
      skeletal muscle. The hypothesis was that AT1R blocking would result in a superior
      myogenic response accompanied by down-regulation of transforming growth factor
      beta and up-regulation of insulin-like growth factor-1 signaling. METHODS: Twenty
      eight healthy elderly men (+64 yr) were randomized into two groups, consuming
      either AT1R blocker (losartan, 100 mg.d) or placebo for 18 d before exercise.
      Participants performed one bout of heavy-unilateral-resistance exercise. Six
      muscle biopsies were obtained from the vastus lateralis muscles of each subject:
      two before exercise and four after exercise (4.5 h and 1, 4, and 7 d). Blood
      pressure and blood samples were collected at the same time points. Biopsies were
      sectioned for immunohistochemistry to determine the number of satellite cells
      associated with Type I and Type II fibers. Gene expression levels of Notch,
      connective tissue, and myogenic signaling pathways were determined by real-time
      reverse transcription polymerase chain reaction. RESULTS: Changes over time were
      detected for circulating creatine kinase, the number of satellite cells per Type
      I fiber, and most of the gene targets, with no specific effect of losartan on
      these. However, when compared with placebo, losartan intake resulted in a greater
      suppression of myostatin messenger RNA. CONCLUSIONS: In general, there does not
      seem to be any effect of AT1R blocking on satellite cell number or myogenic
      pathways in elderly men in the days after one bout of heavy-resistance exercise.
      However, the greater suppression of myostatin may prove to be beneficial over a
      long-term intervention designed to induce hypertrophy.

PMID- 29040225
TI  - Validation of a Novel Device to Measure and Provide Feedback on Sedentary
      Behavior.
AB  - PURPOSE: Pedometers, which enable self-monitoring of step counts, are effective
      in facilitating increases in physical activity. Similar devices which provide
      real-time feedback on sedentary (sitting) behavior are limited. This study aimed
      to develop and validate a novel device-the SitFIT-which could accurately measure
      and provide feedback on sedentary behavior and physical activity. METHODS: The
      SitFIT is a triaxial accelerometer, developed by PAL Technologies, which is worn
      in the front trouser pocket. This enables tracking of thigh inclination and
      therefore differentiation between sitting and upright postures, as well as
      tracking of step count. It has a display to provide user feedback. To determine
      the validity of the SitFIT for measuring sedentary behavior and step counts, 21
      men, age 30 to 65 yr, with body mass index 26.6 +/- 3.9 kg.m wore a SitFIT in a
      front trouser pocket and an activPAL accelerometer attached to their thigh for up
      to 7 d. Outputs from the SitFIT were compared with the activPAL, which was
      assumed to provide criterion standard measurements of sitting and step counts.
      RESULTS: Mean step counts were approximately 4% lower with the SitFIT than
      activPAL, with correlation between the two methods being very high (r = 0.98) and
      no obvious bias from the line of equality (regression line, y = 1.0035x +
      418.35). Mean sedentary time was approximately 5% higher with the SitFIT than
      activPAL, correlation between methods was high (r = 0.84), and the equation of
      the regression line was close to the line of equality (y = 0.8728x + 38.445).
      CONCLUSIONS: The SitFIT has excellent validity for measurement of free-living
      step counts and sedentary time and therefore addresses a clear need for a device
      that can be used as a tool to provide feedback on sedentary behavior to
      facilitate behavior change.

PMID- 29040226
TI  - Propranolol and Oxandrolone Therapy Accelerated Muscle Recovery in Burned
      Children.
AB  - INTRODUCTION: Severe burns result in prolonged hypermetabolism and skeletal
      muscle catabolism. Rehabilitative exercise training (RET) programs improved
      muscle mass and strength in severely burned children. The combination of RET with
      beta-blockade or testosterone analogs showed improved exercise-induced benefits
      on body composition and muscle function. However, the effect of RET combined with
      multiple drug therapy on muscle mass, strength, cardiorespiratory fitness, and
      protein turnover are unknown. In this placebo-controlled randomized trial, we
      hypothesize that RET combined with oxandrolone and propranolol (Oxprop) will
      improve muscle mass and function and protein turnover in severely burned children
      compared with burned children undergoing the same RET with a placebo. METHODS: We
      studied 42 severely burned children (7-17 yr) with severe burns over 30% of the
      total body surface area. Patients were randomized to placebo (22 control) or to
      Oxprop (20) and began drug administration within 96 h of admission. All patients
      began RET at hospital discharge as part of their standardized care. Muscle
      strength (N.m), power (W), VO2peak, body composition, and protein fractional
      synthetic rate and fractional breakdown rate were measured pre-RET (PRE) and post
      RET (POST). RESULTS: Muscle strength and power, lean body mass, and VO2peak
      increased with RET in both groups (P < 0.01). The increase in strength and power
      was significantly greater in Oxprop versus control (P < 0.01), and strength and
      power was greater in Oxprop over control POST (P < 0.05). Fractional synthetic
      rate was significantly higher in Oxprop than control POST (P < 0.01), resulting
      in improved protein net balance POST (P < 0.05). CONCLUSIONS: Rehabilitative
      exercise training improves body composition, muscle function, and
      cardiorespiratory fitness in children recovering from severe burns. Oxprop
      therapy augments RET-mediated improvements in muscle strength, power, and protein
      turnover.

PMID- 29040227
TI  - TESTOSTERONE SUPPLEMENTATION AND RETINAL VASCULAR DISEASE.
AB  - PURPOSE: To determine whether testosterone supplementation is associated with
      retinal artery occlusion (RAO) or retinal vein occlusion (RVO). METHODS:
      Retrospective matched cohort study using data from a large national U.S.
      insurance database. The testosterone cohort consisted of all male patients who
      filled a prescription for testosterone from 2000 to 2013. Five controls were
      matched on age (+/-3 years), sex, race, and similar time in plan (+/-3 months)
      for every exposed patient. Exclusion occurred for <2 years in the plan, <1 eye
      care visit, medications known to affect androgen levels, and systemic diseases
      associated with occlusions or increased testosterone. Cox proportional hazard
      regression assessed the hazard of a new diagnosis of RAO or RVO while controlling
      for age, race, diabetes mellitus, and hypertension. RESULTS: A total of 35,784
      incident testosterone users were compared with 178,860 matched controls. Ninety
      three (0.3%) RAOs and 50 (0.1%) RVOs were found in the testosterone cohort and
      contrasted with 316 (0.2%) RAOs and 232 (0.1%) RVOs in the control group. After
      multivariate analysis, testosterone supplementation significantly increased the
      hazard of RAO (hazard ratio: 1.43, 95% confidence interval: 1.12-1.81, P =
      0.004), but not of RVO (hazard ratio: 1.03, 95% confidence interval: 0.74-1.42, P
      = 0.86). CONCLUSION: Although the incidence of RAO and RVO is low in users of
      testosterone, supplementation therapy is associated with an increased hazard of
      RAO, but apparently not of RVO.

PMID- 29040228
TI  - Analytical Pitfalls of Therapeutic Drug Monitoring of Thiopurines in Patients
      With Inflammatory Bowel Disease.
AB  - The use of thiopurines in the treatment of inflammatory bowel disease (IBD) can
      be optimized by the application of therapeutic drug monitoring. In this
      procedure, 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP)
      metabolites are monitored and related to therapeutic response and adverse events,
      respectively. Therapeutic drug monitoring of thiopurines, however, is hampered by
      several analytical limitations resulting in an impaired translation of metabolite
      levels to clinical outcome in IBD. Thiopurine metabolism is cell specific and
      requires nucleated cells and particular enzymes for 6-TGN formation. In the
      current therapeutic drug monitoring, metabolite levels are assessed in
      erythrocytes, whereas leukocytes are considered the main target cells of these
      drugs. Furthermore, currently used methods do not distinguish between active
      nucleotides and their unwanted residual products. Last, there is a lack of a
      standardized laboratorial procedure for metabolite assessment regarding the
      substantial instability of erythrocyte 6-TGN. To improve thiopurine therapy in
      patients with IBD, it is necessary to understand these limitations and recognize
      the general misconceptions in this procedure.

PMID- 29040229
TI  - Development of a Liquid Chromatography-Tandem Mass Spectrometric Method for
      Quantification of Mycophenolic Acid and Its Glucuronides in Dried Blood Spot
      Samples.
AB  - BACKGROUND: Personalized immunosuppressive therapy, including accurate drug
      dosing based on the drug blood level, leads to better clinical outcomes,
      specifically regarding avoidance of drug-induced adverse effects and maintenance
      of efficacy. Mycophenolic acid (MPA) is used as an immunosuppressant in
      transplantation of various solid organs. The aim of this study was to develop a
      method for quantification of MPA and its metabolites, mycophenolic acid 7-O
      glucuronide (MPAG) and mycophenolic acid acyl glucuronide, in dried blood spot
      (DBS) samples, using liquid chromatography/electrospray ionization/tandem mass
      spectrometry. METHODS: For sample preparation, a microwave-drying approach was
      used to deactivate enzymes and reduce drying time. Blood volume was calculated in
      a DBS disk of 3 mm diameter. Concentrations of analytes in plasma from patients
      receiving mycophenolate mofetil were compared with DBS samples after hematocrit
      correction. RESULTS: The method yielded good recoveries of all 3 analytes (90.3%
      104.2%). Blood volume in the disk was calculated as 3.0 +/- 0.2 MUL. Linearity
      over concentration ranges of 0.1-30 mcg/mL MPA, 0.1-200 mcg/mL MPAG, and 0.125-10
      mcg/mL mycophenolic acid acyl glucuronide was obtained with r >=0.999. Intraday
      and interday variations were less than 14.6%, and accuracy was within +/-11.9%.
      Passing-Bablok analysis showed no significant differences between plasma
      concentrations and DBS concentrations after hematocrit correction of MPA and
      MPAG. CONCLUSIONS: We developed and validated a liquid
      chromatography/electrospray ionization-tandem mass spectrometry method for
      analysis of MPA in DBS samples. The method is useful for monitoring the MPA blood
      level.

PMID- 29040230
TI  - Serum Concentrations of Paliperidone After Administration of the Long-Acting
      Injectable Formulation.
AB  - BACKGROUND: The pharmacokinetics of long-acting intramuscular paliperidone in a
      naturalistic setting is not well documented. The objective of this study was to
      investigate the relationship between dose and serum concentrations of
      paliperidone using data from a routine therapeutic drug monitoring service.
      METHODS: Serum concentration measurements in 310 samples from 110 male and 75
      female patients receiving depot injections of paliperidone were retrospectively
      retrieved from the therapeutic drug monitoring database. RESULTS: The median dose
      was 100 mg every 28 days. The median concentration/dose (C/D) ratio of
      paliperidone was 16.1 (nmol/L)/(mg/d), with a 10-90 percentile range of 7.8-31.0
      (nmol/L)/(mg/d). Dose-adjusted serum concentrations were 33% higher in patients
      65 years or older and more than 50% lower in patients taking the p-glycoprotein
      inducer carbamazepine. There were no significant effects of sex or dose on the
      C/D ratio. The median serum concentrations of paliperidone at the end of the dose
      interval were 31 nmol/L at an intramuscular dose of 50 mg/28 d, 53 nmol/L after a
      dose of 75 mg/28 d, 59 nmol/L after a dose of 100 mg/28 d, and 93 nmol/L after a
      dose of 150 mg/28 d. Forty-five percent of the measurements were lower than the
      suggested therapeutic range of 20-60 ng/mL (47-140 nmol/L). CONCLUSIONS: The data
      show a 4-fold interindividual difference in dose-adjusted serum concentrations
      within the 10-90 percentile range and illustrate the significant effects of age
      and p-glycoprotein induction on the pharmacokinetics of paliperidone. The study
      also indicates that at least in some patients, it might take longer time than
      anticipated to reach steady state.

PMID- 29040231
TI  - Continuous Infraclavicular Brachial Block Versus Single-Shot Nerve Block for
      Distal Radius Surgery: A Prospective Randomized Control Trial.
AB  - OBJECTIVES: To compare the efficacy of an infraclavicular single-shot nerve block
      to a continuous infusion through an OnQ infusion pump for rebound pain (between
      12 and 24 hours postoperatively) and postoperative narcotic analgesia
      requirements in distal radius fractures. DESIGN: Prospective randomized control
      trial. SETTINGS: Performed at 2 hospitals affiliated with a large urban academic
      medical center. PATIENTS: Fifty patients undergoing operative fixation of distal
      radius fractures (OTA/AO type 23B/C). INTERVENTION: Patients were randomized to
      receive either an infraclavicular block as a single shot (SSB group) or a
      continuous infusion through an OnQ pump (OnQ group). MAIN OUTCOME MEASURES:
      Visual analog scale (0-10) pain levels and amount of pain medication taken.
      RESULTS: At all time points after discharge, mean postoperative pain scores were
      lower in the OnQ group versus the SSB group but did not reach statistical
      significance. At 12 hours postoperatively, the SSB group and OnQ group pain
      scores, respectively, were 5.2 and 4.1 (P = 0.1615). At 24 hours, the pain scores
      for the SSB and OnQ group, respectively, were 5.4 and 4.8 (P = 0.1918). At these
      same time points, the Percocet taken were the same at 1.3 and 2.3 (P = 0.8328 and
      0.8617). Overall 5 of 24 patients in the OnQ group had pump malfunctions with 4
      being removed before 48 hours. CONCLUSION: OnQ pump is not associated with
      statistically improved postoperative pain control compared with a single nerve
      block for distal radius fractures and did not address rebound pain. LEVEL OF
      EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 29040232
TI  - In Vitro Effect of Vancomycin on the Viability of Articular Chondrocytes.
AB  - OBJECTIVES: To characterize the in vitro toxicity of vancomycin on articular
      cartilage. METHODS: Osteochondral samples extracted from fresh, juvenile porcine
      stifle (knee) joints were exposed to vancomycin saline concentrations of 2, 5,
      and 10 mg/mL and compared with a saline and nonsaline treated control. Comparison
      of chondrocyte viability was assessed with histology examination of chondrocyte
      degeneration using the Mankin criteria and a live/dead staining using ethidium
      homodimer-2 and calcien acetoxymethylester stain and confocal laser scanning
      microscopy. RESULTS: A comparison of chondrocyte viability in the control sample
      and 2 mg/mL group showed no statistical difference (P = 0.38). The chondrocyte
      toxicity was statistically significantly higher in both the 5 mg/mL (P = 0.003)
      and 10 mg/mL (P < 0.001) experimental groups in comparison to the control sample.
      Chondrocyte death increased in a statistically significant dose-dependent
      fashion. Histologically, the Mankin scores were higher for the saline-treated
      group in comparison to the untreated control group. CONCLUSIONS: Vancomycin is
      toxic to articular chondrocytes in concentrations of 5 mg/mL and greater.
      Strategies for controlling concentration must be developed before routine
      application of topical antibiotics around synovial joints is performed.

PMID- 29040233
TI  - Is the Best Plate a Nail? A Review of 3230 Unstable Intertrochanteric Fractures
      of the Proximal Femur.
AB  - OBJECTIVES: To evaluate the functional outcomes, revision, and mortality rates of
      3 implants used for unstable intertrochanteric hip fractures; the sliding hip
      screw (SHS), with or without a trochanteric stabilization plate (TSP); and a
      cephalomedullary nail (CMN). DESIGN: Multicentre National Prospective Cohort
      Study. SETTING: Northern Ireland. PATIENT/PARTICIPANTS: Patients were identified
      from a prospective database. Fractures were classified according to OTA/AO
      A31A2.2, A2.3, and A3. All patients had a minimum of 12 months of follow-up.
      INTERVENTION: Patients received either an SHS, an SHS in combination with a TSP,
      or a CMN. Implant choice was at the discretion of the operating surgeon. OUTCOME
      MEASURE: Primary outcome was 12-month mortality analyzed by the Kaplan-Meier
      survival analysis. Secondary outcomes included 12-month functional status using a
      validated score and all time revision of implants for any reason. RESULTS: In
      total, 3230 patients met the inclusion criteria (2474 SHS, 158 SHS + TSP, and 598
      CMN). CMN use increased over time, with concomitant reduction in SHS use. There
      was no significant difference in functional outcomes at 12 months (analysis of
      variance, P = 0.177). Although men were significantly younger, they were at a
      higher risk of 12-month mortality. CMNs had statistically significantly lower 12
      month mortality rates (P = 0.0148). The highest revision rate (4.04%) was seen in
      patients treated with SHS alone (P = 0.041). CONCLUSIONS: The use of a CMN in
      unstable intertrochanteric hip fractures conveys the best results in functional
      outcomes, 12-month mortality, and has lower revision rates compared with an SHS
      +/- TSP. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 29040234
TI  - Preventing Wedge Deformities When Treating Intertrochanteric Femur Fractures With
      Intramedullary Devices: A Technical Tip.
AB  - Intertrochanteric femur fractures are common injuries associated with significant
      patient morbidity and mortality and high societal costs. Although intramedullary
      devices have shown promises for treating a wide range of intertrochanteric femur
      fractures, improper technique can lead to malalignment, fracture displacement,
      and/or iatrogenic fractures. In particular, a "wedge effect" has been described,
      in which the passage of conical reamers and the intramedullary nail itself
      results in the distraction of intertrochanteric fragments with lateralization of
      the shaft from the femoral neck and varus malalignment. Here, we describe the
      mechanism by which this deformity is generated and describe techniques for
      preventing it, including the use of a modified starting point and an alternative
      to the conical opening reamers.

PMID- 29040235
TI  - Acetabular Fractures in Children and Adolescents: Comparison of Isolated
      Acetabular Fractures and Acetabular Fractures Associated With Pelvic Ring
      Injuries.
AB  - OBJECTIVES: To compare mechanism of injury, fracture pattern, displacement,
      clinical, and radiographic outcome of isolated acetabular fractures (group 1)
      versus acetabular fractures associated with a pelvic ring injury (group 2).
      DESIGN: Retrospective cohort comparative analysis. SETTING: Private orthopaedic
      practice associated with a level one teaching trauma center. MAIN OUTCOME
      MEASUREMENTS: Mechanism of injury, fracture pattern, displacement and treatment,
      Glasgow Coma Scale, Injury Severity Score, leg length discrepancy (LLD), and hip
      dysplasia. PATIENTS: Thirty-two children (group 1: 12 fractures; group 2: 25)
      were classified as 9 A1, 21 A3, 3 B1, 3 B2, and 1 B3 OTA/AO types. Eighteen
      children (22 fractures) were included with average follow-up of 33.3 months (6
      84). The average age was 12.8 years (4-16). RESULTS: Main fracture pattern (75%)
      in group 1 was a posterior wall fracture (A1) caused by falls and sports in 50%.
      Six socket injuries had a hip dislocation, present only in group 1 (P < 0.001).
      The majority (84%) in group 2 had anterior wall/column (A3) fractures, caused by
      traffic accidents (88%). Fracture displacement in group 1 was higher than in
      group 2 (3.8 vs. 0.8 mm; P = 0.009). Group 2 had a lower Glasgow Coma Scale (P =
      0.031) and a higher Injury Severity Score (P < 0.001). Nine (24%) fractures were
      treated operatively, significantly more were in group 1 (P < 0.001). Three (14%)
      children had complications including (LLD) (2) or hip dysplasia (2). CONCLUSION:
      Compared with isolated pediatric acetabular fractures, fractures associated with
      pelvic ring injuries have less displacement and are less likely to require
      operative treatment, but they show more associated injuries. Because of potential
      hip joint growth disturbance, LLD and hip dysplasia can occur. LEVEL OF EVIDENCE:
      Prognostic Level III. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 29040236
TI  - Sprint Interval Training: What are the Clinical Implications and Precautions?

PMID- 29040237
TI  - Response.

PMID- 29040238
TI  - Routine Screening for Iron Deficiency Is an Important Component of Athlete Care.

PMID- 29040239
TI  - Response.

PMID- 29040240
TI  - Low Energy Availability in a Sleep-Low Training Study.

PMID- 29040241
TI  - Barriers to Implementation of Recommendations for Transport of Children in Ground
      Ambulances.
AB  - OBJECTIVES: The National Highway Traffic Safety Administration (NHTSA) released
      draft recommendations in 2010 on the safe transport of children in ground
      ambulances. The purpose of this study was to assess awareness of these guidelines
      among emergency medical service (EMS) agencies and to identify implementation
      barriers. METHODS: We conducted a cross-sectional, anonymous online survey of 911
      responding, ground transport EMS agencies in Texas. Demographics, modes of
      transport based on case scenarios, and barriers to implementation were assessed.
      RESULTS: Of 62 eligible EMS agencies that took the survey, 35.7% were aware of
      the NHTSA guidelines, 62.5% agreed they would improve safety, and 41.1% planned
      to implement them. Seventy-five percent of EMS agencies used the ideal or
      acceptable alternative to transport children requiring continuous monitoring, and
      69.5% chose ideal or acceptable alternatives for children requiring spinal
      immobilization. The ideal or acceptable alternative was not chosen for children
      who were not injured or ill (93.2%), ill or injured but not requiring continuous
      monitoring (53.3%), and situations when multiple patients required transport
      (57.6%). The main requirements for implementation were provider education,
      ambulance interior modifications, new guidelines in the EMS agency, and purchase
      of new equipment. CONCLUSIONS: Few EMS agencies are aware of the NHTSA guidelines
      on safe transport of children in ground ambulances. Although most agencies
      appropriately transport children who require monitoring, interventions, or spinal
      immobilization, they use inappropriate means to transport children in situations
      with multiple patients, lack of injury or illness, or lack of need for
      monitoring.

PMID- 29040242
TI  - Epidemiology and Predictors of Orbital Fractures in Children.
AB  - OBJECTIVES: Data regarding clinical predictors of orbital fractures in children
      are limited. We sought to describe the epidemiology of pediatric orbital
      fractures and identify the signs and symptoms of orbital fractures in children.
      METHODS: We performed a retrospective cohort study of children younger than 22
      years who underwent a facial or orbital computed tomography (CT) scan to evaluate
      for orbital fracture. We included patients presenting to an emergency department
      of a tertiary care children's hospital between January 2009 and May 2013. The
      presence of an orbital fracture was assessed using the final interpretation of
      the CT by an attending radiologist in the electronic medical record. RESULTS:
      Among 326 children who underwent facial or orbital CT during the study period,
      133 (41%) had an orbital fracture. The presence of nausea or vomiting, orbital
      tenderness, swelling, or ecchymosis and limitation of extraocular movement were
      each associated with the presence of an orbital fracture (P < 0.05 for each).
      Twenty-two children (6.7% of cohort and 16.5% of children with orbital fractures)
      underwent surgical repair for an orbital fracture. In the absence of orbital
      tenderness, swelling, or ecchymosis, there was 1 child with an orbital fracture
      who underwent operative intervention. CONCLUSIONS: Fewer than half of children
      undergoing CT have an orbital fracture identified, and fewer than 7% have a
      fracture that requires operative intervention. In the absence of orbital
      tenderness, swelling, or ecchymosis, only 1 child had an orbital fracture
      requiring surgical repair.

PMID- 29040243
TI  - Toxic Shock Syndrome: Still a Timely Diagnosis.
AB  - BACKGROUND: Toxic shock syndrome (TSS) is an acute, severe, toxin-mediated
      disease, characterized by fever, hypotension, and multiorgan system involvement.
      Toxic shock syndrome has made headlines because of its high associated morbidity
      and mortality rate in previously healthy young females. Incidence peaked in the
      early 1980s owing to increased usage of ultra-absorbent tampons. After improved
      patient education and tampon labeling, the incidence of menstrual TSS has
      declined. CASE: A previously healthy 14-year-old girl presented to an urgent care
      center with a 2-day history of fever, erythematous maculopapular rash, vomiting,
      diarrhea, and malaise. She was found to be tachycardic and hypotensive.
      Investigations revealed thrombocytopenia, an elevated white count and lactate,
      and acute kidney injury, consistent with septic shock. Recent tampon usage with
      menstruation was reported, and a pelvic examination revealed purulent vaginal
      discharge. The patient was transferred to a pediatric intensive care unit for
      antibiotic and vasopressor therapy. Vaginal swabs later tested positive for
      Staphylococcus aureus and TSS toxin-1. CONCLUSIONS: Although the incidence of TSS
      has decreased in recent years, it is crucial that clinicians rapidly recognize
      and treat this life-threatening condition. Emergency physicians should always
      have a high index of suspicion for TSS in young females presenting without
      another obvious cause of shock. A pelvic examination should always be completed
      in these cases.

PMID- 29040244
TI  - A Prospective Study of the Causes of Bruises in Premobile Infants.
AB  - OBJECTIVE: This study had 2 objectives. First, to determine the behavior of
      physicians evaluating premobile infants with bruises. Second, and most
      importantly, to learn whether infants with unexplained bruising who had been
      initially evaluated by primary care and emergency department (ED) physicians are
      as likely to have their bruises attributed to child abuse as those children
      evaluated by child abuse physicians. METHODS: Primary care, ED, and child abuse
      pediatricians (CAPs) in King County, Washington, San Mateo, Calif, Albuquerque,
      NM, La Crosse, Wis, and Torrance, Calif prospectively identified and studied
      infants younger than 6 months with less than 6 bruises, which were judged by the
      evaluating clinician to be explained or unexplained after their initial clinical
      examination. RESULTS: Between March 1, 2010, and March 1, 2017, 63 infants with
      initially explained and 46 infants with initially unexplained bruises were
      identified. Infants with unexplained bruises had complete coagulation and abuse
      evaluations less frequently if they were initially identified by primary care
      pediatricians or ED providers than by CAPs. After imaging, laboratory, and follow
      up, 54.2% (26) of the infants with initially unexplained bruises, including 2 who
      had been initially diagnosed with accidental injuries, were diagnosed as abused.
      Three (6.2%) infants had accidental bruising, 6 (12.4%) abuse mimics, 1 (2.5%)
      self-injury, 1 (2.5%) medical injury, and 11 (22.9%) remained of unknown
      causation. None had causal coagulation disorders. A total of 65.4% of the 26
      abused infants had occult injuries detected by their imaging and laboratory
      evaluations. Six (23.1%) abused infants were not diagnosed until after they
      sustained subsequent injuries. Three (11.5%) were recognized abused by police
      investigation alone. Thirty-eight percent of the abused, bruised infants had a
      single bruise. Clinicians' estimates of abuse likelihood based on their initial
      clinical evaluation were inaccurate. Primary care, ED, and child abuse physicians
      identified abused infants at similar rates. CONCLUSIONS: More than half of
      premobile infants with initially unexplained bruises were found to be abused.
      Abuse was as likely for infants identified by primary care and ED providers as
      for those identified by CAPs. Currently, physicians often do not obtain full
      abuse evaluations in premobile infants with unexplained bruising. Their initial
      clinical judgment about abuse likelihood was inadequate. Bruised infants often
      have clinically occult abusive injuries or will sustain subsequent serious abuse.
      Bruised infants should have full abuse evaluations and referral for Protective
      Services and police assessments.

PMID- 29040245
TI  - Code Team Training: Demonstrating Adherence to AHA Guidelines During Pediatric
      Code Blue Activations.
AB  - OBJECTIVE: Pediatric code blue activations are infrequent events with a high
      mortality rate despite the best effort of code teams. The best method for
      training these code teams is debatable; however, it is clear that training is
      needed to assure adherence to American Heart Association (AHA) Resuscitation
      Guidelines and to prevent the decay that invariably occurs after Pediatric
      Advanced Life Support training. The objectives of this project were to train a
      multidisciplinary, multidepartmental code team and to measure this team's
      adherence to AHA guidelines during code simulation. METHODS: Multidisciplinary
      code team training sessions were held using high-fidelity, in situ simulation.
      Sessions were held several times per month. Each session was filmed and reviewed
      for adherence to 5 AHA guidelines: chest compression rate, ventilation rate,
      chest compression fraction, use of a backboard, and use of a team leader. After
      the first study period, modifications were made to the code team including
      implementation of just-in-time training and alteration of the compression team.
      RESULTS: Thirty-eight sessions were completed, with 31 eligible for video
      analysis. During the first study period, 1 session adhered to all AHA guidelines.
      During the second study period, after alteration of the code team and
      implementation of just-in-time training, no sessions adhered to all AHA
      guidelines; however, there was an improvement in percentage of sessions adhering
      to ventilation rate and chest compression rate and an improvement in median
      ventilation rate. CONCLUSIONS: We present a method for training a large code team
      drawn from multiple hospital departments and a method of assessing code team
      performance. Despite subjective improvement in code team positioning,
      communication, and role completion and some improvement in ventilation rate and
      chest compression rate, we failed to consistently demonstrate improvement in
      adherence to all guidelines.

PMID- 29040246
TI  - A Rare Case of Cecal Bascule in a Child With Normal Neurodevelopment.
AB  - Cecal volvulus is a rare cause of bowel obstruction in adults and an extremely
      rare presentation in children. One form known as a cecal bascule has only
      previously been reported in children with neurodevelopmental issues or with
      severe chronic constipation. We present the case of a 10-year-old boy who
      presented with an acute history of left lower quadrant abdominal pain, who upon
      investigation was found to have a cecal bascule.

PMID- 29040247
TI  - Use of Ondansetron for Vomiting After Head Trauma: Does It Mask Clinically
      Significant Traumatic Brain Injury?
AB  - OBJECTIVES: We describe ondansetron use in children with head injury evaluated in
      pediatric emergency departments and its association with return visits and late
      diagnoses of intracranial injuries requiring intervention. METHODS: Children ages
      6 months to 18 years discharged without neuroimaging from 35 pediatric emergency
      departments with a diagnosis of head injury from 2009 to 2013 were identified
      retrospectively from the Pediatric Health Information System. We evaluated the
      rates of ondansetron use during the study period and of the association of
      ondansetron treatment with the diagnosis of intracranial injury, skull fracture,
      and return visits within 72 hours requiring admission or operative intervention.
      RESULTS: We identified 218,904 encounters during the study period. Of these, 5894
      patients (2.8%) were given ondansetron. There was significant variation in the
      use of ondansetron during the index visit between hospitals (0.1%-5.7%), and
      ondansetron use significantly increased over the study period. Return visits
      within 72 hours were more likely for patients treated with ondansetron during the
      index visit (3.7% vs 1.9%; adjusted odds ratio, 1.99; 95% confidence interval,
      1.7-2.4). These patients were more likely to be admitted than those not treated
      initially with ondansetron (7% vs 4%; adjusted odds ratio, 1.97; 95% confidence
      interval, 1.09-3.55). There were no significant differences in rates of skull
      fractures, intracranial injury, intensive care unit admission, or operative
      intervention between groups. CONCLUSIONS: Ondansetron use during an initial
      emergency department visit for head trauma in children not requiring neuroimaging
      is associated with a higher likelihood of return within 72 hours and subsequent
      admission. There were no differences in rates of missed skull fractures,
      intracranial injury, intensive care admission, or operative intervention for
      groups who were and were not treated with ondansetron; however, this study was
      underpowered to detect significant differences in these categories. Future
      investigations with greater numbers would be required to confidently assess these
      critical differences.

PMID- 29040248
TI  - Retrospective Evaluation of Surgical Anatomical Repair of Distal Biceps Brachii
      Tendon Rupture Using Suture Anchor Fixation.
AB  - BACKGROUND To date, no consensus has been reached regarding the preferred
      fixation method to use in the repair of distal biceps brachii tendon rupture. The
      aim of this study was to clinically and functionally (Mayo Elbow Performance
      Index, MEPI) assess the upper limb after surgical anatomic reinsertion of the
      distal biceps brachii tendon with the use of suture anchor fixation method with
      regard to postoperative time and limb dominance, and to assess postoperative
      complications. MATERIAL AND METHODS The sample comprised 18 males (age 52.09+/
      8.89 years) after surgical anatomical distal biceps brachii reinsertion using
      suture anchor fixation. A comprehensive clinical and functional evaluation and
      pain assessment were performed. RESULTS In terms of postoperative complications,
      an isolated case of surgical site sensory disturbances was noted. Circumferences
      (p-value 0.21-1.00) and ROM (p-value 0.07-1.00) were similar in the operated and
      nonoperated limbs. The isometric torque (IT) values of muscles flexing and
      supinating the forearm were comparable in both limbs (p-value 0.14-0.95), but in
      patients with the operated dominant limb, the mean IT value was not higher than
      the value obtained in the nonoperated nondominant one. The MEPI indicated good
      and excellent results (80.00+/-15.00-90.00+/-8.66 points), but a detailed
      individual analysis showed that reported scores were not in line with objectively
      measured features. CONCLUSIONS The results of the comprehensive retrospective
      evaluation justify the clinical use of suture anchors fixation method in the
      surgical anatomical reinsertion of a ruptured distal biceps brachii tendon. The
      assessment of a patient should always report both subjective and objective
      measures.

PMID- 29040251
TI  - What is the optimal duration of adjuvant therapy in colon cancer?

PMID- 29040252
TI  - In the pipeline: encorafenib and binimetinib in BRAF-mutated melanoma.

PMID- 29040253
TI  - Direct-to-consumer advertising of cancer treatments.

PMID- 29040254
TI  - When to initiate treatment in smoldering multiple myeloma.

PMID- 29040255
TI  - How I treat stage IV non-small cell lung cancer in the absence of any actionable
      oncogenic driver.

PMID- 29040256
TI  - The role of genomics in patients with advanced prostate cancer.

PMID- 29040257
TI  - Current challenges in the management of essential thrombocythemia.
AB  - Essential thrombocythemia (ET), an uncommon blood cancer, is one of the classic
      myeloproliferative neoplasms, a category that also includes polycythemia vera and
      primary myelofibrosis. All 3 diseases are clonal hematopoietic stem cell
      disorders. Since 2005, when scientists discovered a molecular aberration driving
      clonal hematopoiesis in polycythemia vera, our understanding of the genomic
      underpinnings of these conditions has increased rapidly. Over the last decades,
      primary prevention of thrombotic and hemorrhagic complications has improved the
      lives of patients with ET, and the ability to characterize the disease by the
      presence or absence of molecular mutations has lent precision to our prognostic
      models. This review outlines a modern approach to the diagnosis and treatment of
      ET. It highlights the 2016 World Health Organization standards for
      differentiating the disease from primary myelofibrosis, which is key for an
      accurate prognosis. It also describes the current risk stratification models and
      discusses the vascular and hemorrhagic risks that affect patients with this
      chronic condition, including younger individuals and pregnant women. Finally, it
      outlines a simple-to-follow treatment algorithm that is based on an understanding
      of the vascular risks and provides a foundation for discussing treatment choices
      with patients.

PMID- 29040258
TI  - Prognostic and therapeutic implications of DNA repair gene mutations in advanced
      prostate cancer.
AB  - Recent work directed toward understanding the molecular features of advanced
      prostate cancers has revealed a relatively high incidence of both germline and
      somatic alterations in genes involved in DNA damage repair (DDR). Many of these
      alterations likely play a critical role in the pathogenesis of more aggressive
      prostate cancers-leading to genomic instability and an increased probability of
      the development of lethal disease. However, because the ability to repair DNA
      damage with a high degree of fidelity is critical to an individual cell's
      survival, tumor cells harboring alterations in DDR pathway genes are also more
      susceptible to drugs that induce DNA damage or impair alternative DNA repair
      pathways. In addition, because the genomic instability that results from these
      alterations can lead to an inherently higher number of mutations than occur in
      cells with intact DDR pathways, patients with genomic instability may be more
      likely to respond to immune checkpoint inhibitors, presumably owing to a
      correspondingly high neoantigen burden. In this review, we discuss the emerging
      molecular taxonomy that is providing a framework for precision oncology
      initiatives aimed at developing targeted approaches for treating prostate cancer.

PMID- 29040261
TI  - Effects of growth hormone treatment on growth plate, bone, and mineral metabolism
      of young rats with uremia induced by adenine.
AB  - This corrects the article DOI: 10.1038/pr.2017.95.

PMID- 29040259
TI  - Introduction of various allergenic foods during infancy reduces risk of IgE
      sensitization at 12 months of age: a birth cohort study.
AB  - BackgroundIn this study, we aimed to determine whether introducing various
      allergenic foods during infancy is associated with IgE sensitization at 12 months
      of age.MethodsDetailed information on feeding practices regarding six possible
      allergenic foods (fruits, egg white, egg yolk, fish, shellfish, and peanuts) was
      obtained by administering age-specific questionnaires to parents of infants at
      ages 6 and 12 months. Fecal secretory IgA (sIgA), fecal eosinophil cationic
      protein (ECP), and serum levels of total IgE and IgE specific to 20 foods, and
      IgE specific to 20 inhalant allergens were also quantified at 12 months of
      age.ResultsAt 12 months of age, infants with IgE sensitization had been
      introduced to fewer allergenic food items during infancy (3.2+/-1.4 vs. 3.7+/-1.3
      items). Compared with infants who were given 0-2 allergenic food items, infants
      introduced to 3-4 or >=5 allergenic food items showed a significantly lower risk
      of IgE sensitization (odds ratios (ORs) 0.62 and 0.61, respectively) and lower
      total IgE levels. In addition, non-introduction of egg white or egg yolk was
      significantly related to IgE sensitization (ORs 1.41 and 1.26,
      respectively).ConclusionIncreasing the diversity of allergenic foods in infancy,
      including fruits, egg white, egg yolk, fish, shellfish, and peanuts, may protect
      infants from IgE sensitization at 12 months of age.

PMID- 29040262
TI  - Serological and spatial analysis of alphavirus and flavivirus prevalence and risk
      factors in a rural community in western Kenya.
AB  - Alphaviruses, such as chikungunya virus, and flaviviruses, such as dengue virus,
      are (re)-emerging arboviruses that are endemic in tropical environments. In
      Africa, arbovirus infections are often undiagnosed and unreported, with febrile
      illnesses often assumed to be malaria. This cross-sectional study aimed to
      characterize the seroprevalence of alphaviruses and flaviviruses among children
      (ages 5-14, n = 250) and adults (ages 15 >= 75, n = 250) in western Kenya. Risk
      factors for seropositivity were explored using Lasso regression. Overall, 67% of
      participants showed alphavirus seropositivity (CI95 63%-70%), and 1.6% of
      participants showed flavivirus seropositivity (CI95 0.7%-3%). Children aged 10-14
      were more likely to be seropositive to an alphavirus than adults (p < 0.001),
      suggesting a recent transmission period. Alphavirus and flavivirus seropositivity
      was detected in the youngest participants (age 5-9), providing evidence of inter
      epidemic transmission. Demographic variables that were significantly different
      amongst those with previous infection versus those without infection included
      age, education level, and occupation. Behavioral and environmental variables
      significantly different amongst those in with previous infection to those without
      infection included taking animals for grazing, fishing, and recent village
      flooding. Experience of recent fever was also found to be a significant indicator
      of infection (p = 0.027). These results confirm alphavirus and flavivirus
      exposure in western Kenya, while illustrating significantly higher alphavirus
      transmission compared to previous studies.

PMID- 29040263
TI  - Tuberculosis detection and the challenges of integrated care in rural China: A
      cross-sectional standardized patient study.
AB  - BACKGROUND: Despite recent reductions in prevalence, China still faces a
      substantial tuberculosis (TB) burden, with future progress dependent on the
      ability of rural providers to appropriately detect and refer TB patients for
      further care. This study (a) provides a baseline assessment of the ability of
      rural providers to correctly manage presumptive TB cases; (b) measures the gap
      between provider knowledge and practice and; (c) evaluates how ongoing reforms of
      China's health system-characterized by a movement toward "integrated care" and
      promotion of initial contact with grassroots providers-will affect the care of TB
      patients. METHODS/FINDINGS: Unannounced standardized patients (SPs) presenting
      with classic pulmonary TB symptoms were deployed in 3 provinces of China in July
      2015. The SPs successfully completed 274 interactions across all 3 tiers of
      China's rural health system, interacting with providers in 46 village clinics,
      207 township health centers, and 21 county hospitals. Interactions between
      providers and standardized patients were assessed against international and
      national standards of TB care. Using a lenient definition of correct management
      as at least a referral, chest X-ray or sputum test, 41% (111 of 274) SPs were
      correctly managed. Although there were no cases of empirical anti-TB treatment,
      antibiotics unrelated to the treatment of TB were prescribed in 168 of 274
      interactions or 61.3% (95% CI: 55%-67%). Correct management proportions
      significantly higher at county hospitals compared to township health centers (OR
      0.06, 95% CI: 0.01-0.25, p < 0.001) and village clinics (OR 0.02, 95% CI: 0.0
      0.17, p < 0.001). Correct management in tests of knowledge administered to the
      same 274 physicians for the same case was 45 percentage points (95% CI: 37%-53%)
      higher with 24 percentage points (95% CI: -33% to -15%) fewer antibiotic
      prescriptions. Relative to the current system, where patients can choose to
      bypass any level of care, simulations suggest that a system of managed referral
      with gatekeeping at the level of village clinics would reduce proportions of
      correct management from 41% to 16%, while gatekeeping at the level of the
      township hospital would retain correct management close to current levels at 37%.
      The main limitations of the study are 2-fold. First, we evaluate the management
      of a one-time new patient presenting with presumptive TB, which may not reflect
      how providers manage repeat patients or more complicated TB presentations.
      Second, simulations under alternate policies require behavioral and statistical
      assumptions that should be addressed in future applications of this method.
      CONCLUSIONS: There were significant quality deficits among village clinics and
      township health centers in the management of a classic case of presumptive TB,
      with higher proportions of correct case management in county hospitals. Poor
      clinical performance does not arise only from a lack of knowledge, a phenomenon
      known as the "know-do" gap. Given significant deficits in quality of care,
      reforms encouraging first contact with lower tiers of the health system can
      improve efficiency only with concomitant improvements in appropriate management
      of presumptive TB patients in village clinics and township health centers.

PMID- 29040264
TI  - Comparison of pulmonary vascular permeability index PVPI and global ejection
      fraction GEF derived from jugular and femoral indicator injection using the PiCCO
      2 device: A prospective observational study.
AB  - BACKGROUND: Transpulmonary thermodilution (TPTD) is used to derive cardiac output
      CO, global end-diastolic volume GEDV and extravascular lung water EVLW. To
      facilitate interpretation of these data, several ratios have been developed,
      including pulmonary vascular permeability index (defined as EVLW/(0.25*GEDV)) and
      global ejection fraction ((4*stroke volume)/GEDV). PVPI and GEF have been
      associated to the aetiology of pulmonary oedema and systolic cardiac function,
      respectively. Several studies demonstrated that the use of femoral venous access
      results in a marked overestimation of GEDV. This also falsely reduces PVPI and
      GEF. One of these studies suggested a correction formula for femoral venous
      access that markedly reduced the bias for GEDV. Consequently, the last PiCCO
      algorithm requires information about the CVC, and correction for femoral access
      has been shown. However, two recent studies demonstrated inconsistencies of the
      last PiCCO algorithm using incorrected GEDV for PVPI, but corrected GEDV for GEF.
      Nevertheless, these studies were based on mathematical analyses of data displayed
      in a total of 15 patients equipped with only a femoral, but not with a jugular
      CVC. Therefore, this study compared PVPI_fem and GEF_fem derived from femoral
      TPTD to values derived from jugular indicator injection in 25 patients with both
      jugular and femoral CVCs. METHODS: 54 datasets in 25 patients were recorded. Each
      dataset consisted of three triplicate TPTDs using the jugular venous access as
      the gold standard and the femoral access with (PVPI_fem_cor) and without
      (PVPI_fem_uncor) information about the femoral indicator injection to evaluate,
      if correction for femoral GEDV pertains to PVPI_fem and GEF_fem. RESULTS:
      PVPI_fem_uncor was significantly lower than PVPI_jug (1.48+/-0.47 vs. 1.84+/
      0.53; p<0.001). Similarly, PVPI_fem_cor was significantly lower than PVPI_jug
      (1.49+/-0.46 vs. 1.84+/-0.53; p<0.001). This is explained by the finding that
      PVPI_fem_uncor was not different to PVPI_fem_cor (1.48+/-0.47 vs. 1.49+/-0.46;
      n.s.). This clearly suggests that correction for femoral CVC does not pertain to
      PVPI. GEF_fem_uncor was significantly lower than GEF_jug (20.6+/-5.1% vs. 25.0+/
      6.1%; p<0.001). By contrast, GEF_fem_cor was not different to GEF_jug (25.6+/
      5.8% vs. 25.0+/-6.1%; n.s.). Furthermore, GEF_fem_cor was significantly higher
      than GEF_fem_uncor (25.6+/-5.8% vs. 20.6+/-5.1%; p<0.001). This finding
      emphasizes that an appropriate correction for femoral CVC is applied to
      GEF_fem_cor. The extent of the correction (25.5/20.6; 124%) for GEF and the
      relation of PVPI_jug/PVPI_fem_uncor (1.84/1.48; 124%) are in the same range as
      the ratio of GEDVI_fem_uncor/GEDVI_fem_cor (1056ml/m2/821mL/m2; 129%). This
      further emphasizes that GEF, but not PVPI is corrected in case of femoral
      indicator injection. CONCLUSIONS: Femoral indicator injection for TPTD results in
      significantly lower values for PVPI and GEF. While the last PiCCO algorithm
      appropriately corrects GEF, the correction is not applied to PVPI. Therefore, GEF
      values can be used in case of femoral CVC, but PVPI-values are substantially
      underestimated.

PMID- 29040265
TI  - Analysis of peripheral B cells and autoantibodies against the anti-nicotinic
      acetylcholine receptor derived from patients with myasthenia gravis using single
      cell manipulation tools.
AB  - The majority of patients with myasthenia gravis (MG), an organ-specific
      autoimmune disease, harbor autoantibodies that attack the nicotinic acetylcholine
      receptor (nAChR-Abs) at the neuromuscular junction of skeletal muscles, resulting
      in muscle weakness. Single cell manipulation technologies coupled with genetic
      engineering are very powerful tools to examine T cell and B cell repertoires and
      the dynamics of adaptive immunity. These tools have been utilized to develop mAbs
      in parallel with hybridomas, phage display technologies and B-cell
      immortalization. By applying a single cell technology and novel high-throughput
      cell-based binding assays, we identified peripheral B cells that produce
      pathogenic nAChR-Abs in patients with MG. Although anti-nAChR antibodies produced
      by individual peripheral B cells generally exhibited low binding affinity for the
      alpha-subunit of the nAChR and great sequence diversity, a small fraction of
      these antibodies bound with high affinity to native-structured nAChRs on cell
      surfaces. B12L, one such Ab isolated here, competed with a rat Ab (mAb35) for
      binding to the human nAChR and thus considered to recognize the main immunogenic
      region (MIR). By evaluating the Ab in in vitro cell-based assays and an in vivo
      rat passive transfer model, B12L was found to act as a pathogenic Ab in rodents
      and presumably in humans.These findings suggest that B cells in peripheral blood
      may impact MG pathogenicity. Our methodology can be applied not only to validate
      pathogenic Abs as molecular target of MG treatment, but also to discover and
      analyze Ab production systems in other human diseases.

PMID- 29040266
TI  - Chinese college freshmen's mental health problems and their subsequent help
      seeking behaviors: A cohort design (2005-2011).
AB  - Based on cohort data obtained from 13,085 college freshmen's (2005 to 2011) SCL
      90 (the Symptom Check-List-90) reports and their subsequent 4-year psychological
      counseling help-seeking records, this study examined the association between
      college students' mental health problems and help-seeking behaviors across four
      college years. Female students' mental health problems and help-seeking behaviors
      increased from the 2005 to the 2011 cohorts and no changes emerged for male
      students across cohorts. Overall, male students reported higher levels of mental
      health problems than did female students in the first college year, whereas
      female students reported more help-seeking behaviors than did male students in
      the following four college years. College students' mental health problems was
      associated positively with help-seeking behaviors. College students were more
      likely to seek help from the college psychological counselling center when they
      experienced relatively few or quite a lot of mental health issues (i.e., an
      inversed U shape). Implications for future studies and practices are discussed.

PMID- 29040267
TI  - Protecting cows in small holder farms in East Africa from tsetse flies by
      mimicking the odor profile of a non-host bovid.
AB  - BACKGROUND: For the first time, differential attraction of pathogen vectors to
      vertebrate animals is investigated for novel repellents which when applied to
      preferred host animals turn them into non-hosts thereby providing a new paradigm
      for innovative vector control. For effectively controlling tsetse flies (Glossina
      spp.), vectors of African trypanosomosis, causing nagana, repellents more
      powerful than plant derived, from a non-host animal the waterbuck, Kobus
      ellipsiprymnus defassa, have recently been identified. Here we investigate these
      repellents in the field to protect cattle from nagana by making cattle as
      unattractive as the buck. METHODOLOGY/PRINCIPAL FINDINGS: To dispense the
      waterbuck repellents comprising guaiacol, geranylacetone, pentanoic acid and
      delta-octalactone, (patent application) we developed an innovative collar-mounted
      release system for individual cattle. We tested protecting cattle, under natural
      tsetse challenge, from tsetse transmitted nagana in a large field trial
      comprising 1,100 cattle with repellent collars in Kenya for 24 months. The
      collars provided substantial protection to livestock from trypanosome infection
      by reducing disease levels >80%. Protected cattle were healthier, showed
      significantly reduced disease levels, higher packed cell volume and significantly
      increased weight. Collars >60% reduced trypanocide use, 72.7% increase in
      ownership of oxen per household and enhanced traction power (protected animals
      ploughed 66% more land than unprotected). Land under cultivation increased by
      73.4%. Increase in traction power of protected animals reduced by 69.1% acres
      tilled by hand per household per ploughing season. Improved food security and
      household income from very high acceptance of collars (99%) motivated the farmers
      to form a registered community based organization promoting collars for
      integrated tsetse control and their commercialization. CONCLUSION/SIGNIFICANCE:
      Clear demonstration that repellents from un-preferred hosts prevent contact
      between host and vector, thereby preventing disease transmission: a new paradigm
      for vector control. Evidence that deploying water buck repellents converts cattle
      into non-hosts for tsetse flies-'cows in waterbuck clothing'.

PMID- 29040268
TI  - Benefit and harm of intensive blood pressure treatment: Derivation and validation
      of risk models using data from the SPRINT and ACCORD trials.
AB  - BACKGROUND: Intensive blood pressure (BP) treatment can avert cardiovascular
      disease (CVD) events but can cause some serious adverse events. We sought to
      develop and validate risk models for predicting absolute risk difference
      (increased risk or decreased risk) for CVD events and serious adverse events from
      intensive BP therapy. A secondary aim was to test if the statistical method of
      elastic net regularization would improve the estimation of risk models for
      predicting absolute risk difference, as compared to a traditional backwards
      variable selection approach. METHODS AND FINDINGS: Cox models were derived from
      SPRINT trial data and validated on ACCORD-BP trial data to estimate risk of CVD
      events and serious adverse events; the models included terms for intensive BP
      treatment and heterogeneous response to intensive treatment. The Cox models were
      then used to estimate the absolute reduction in probability of CVD events
      (benefit) and absolute increase in probability of serious adverse events (harm)
      for each individual from intensive treatment. We compared the method of elastic
      net regularization, which uses repeated internal cross-validation to select
      variables and estimate coefficients in the presence of collinearity, to a
      traditional backwards variable selection approach. Data from 9,069 SPRINT
      participants with complete data on covariates were utilized for model
      development, and data from 4,498 ACCORD-BP participants with complete data were
      utilized for model validation. Participants were exposed to intensive (goal
      systolic pressure < 120 mm Hg) versus standard (<140 mm Hg) treatment. Two
      composite primary outcome measures were evaluated: (i) CVD events/deaths
      (myocardial infarction, acute coronary syndrome, stroke, congestive heart
      failure, or CVD death), and (ii) serious adverse events (hypotension, syncope,
      electrolyte abnormalities, bradycardia, or acute kidney injury/failure). The
      model for CVD chosen through elastic net regularization included interaction
      terms suggesting that older age, black race, higher diastolic BP, and higher
      lipids were associated with greater CVD risk reduction benefits from intensive
      treatment, while current smoking was associated with fewer benefits. The model
      for serious adverse events chosen through elastic net regularization suggested
      that male sex, current smoking, statin use, elevated creatinine, and higher
      lipids were associated with greater risk of serious adverse events from intensive
      treatment. SPRINT participants in the highest predicted benefit subgroup had a
      number needed to treat (NNT) of 24 to prevent 1 CVD event/death over 5 years
      (absolute risk reduction [ARR] = 0.042, 95% CI: 0.018, 0.066; P = 0.001), those
      in the middle predicted benefit subgroup had a NNT of 76 (ARR = 0.013, 95% CI: 
      0.0001, 0.026; P = 0.053), and those in the lowest subgroup had no significant
      risk reduction (ARR = 0.006, 95% CI: -0.007, 0.018; P = 0.71). Those in the
      highest predicted harm subgroup had a number needed to harm (NNH) of 27 to induce
      1 serious adverse event (absolute risk increase [ARI] = 0.038, 95% CI: 0.014,
      0.061; P = 0.002), those in the middle predicted harm subgroup had a NNH of 41
      (ARI = 0.025, 95% CI: 0.012, 0.038; P < 0.001), and those in the lowest subgroup
      had no significant risk increase (ARI = -0.007, 95% CI: -0.043, 0.030; P = 0.72).
      In ACCORD-BP, participants in the highest subgroup of predicted benefit had
      significant absolute CVD risk reduction, but the overall ACCORD-BP participant
      sample was skewed towards participants with less predicted benefit and more
      predicted risk than in SPRINT. The models chosen through traditional backwards
      selection had similar ability to identify absolute risk difference for CVD as the
      elastic net models, but poorer ability to correctly identify absolute risk
      difference for serious adverse events. A key limitation of the analysis is the
      limited sample size of the ACCORD-BP trial, which expanded confidence intervals
      for ARI among persons with type 2 diabetes. Additionally, it is not possible to
      mechanistically explain the physiological relationships explaining the
      heterogeneous treatment effects captured by the models, since the study was an
      observational secondary data analysis. CONCLUSIONS: We found that predictive
      models could help identify subgroups of participants in both SPRINT and ACCORD-BP
      who had lower versus higher ARRs in CVD events/deaths with intensive BP
      treatment, and participants who had lower versus higher ARIs in serious adverse
      events.

PMID- 29040269
TI  - Elevated blood pressure and risk of mitral regurgitation: A longitudinal cohort
      study of 5.5 million United Kingdom adults.
AB  - BACKGROUND: Mitral regurgitation in people without prior cardiac disease is
      considered a degenerative disease with no established risk factors for its
      prevention. We aimed to test the hypothesis that elevated systolic blood pressure
      (SBP) across its usual spectrum is associated with higher risk of mitral
      regurgitation. METHODS AND FINDINGS: We used linked electronic health records
      from the United Kingdom Clinical Practice Research Datalink (CPRD) from 1 January
      1990 to 31 December 2015. CPRD covers approximately 7% of the current UK
      population and is broadly representative of the population by age, sex, and
      ethnicity. About 5.5 million UK patients with no known cardiovascular or valve
      disease at baseline were included in this cohort study. We investigated the
      relationship between blood pressure (BP) and risk of mitral regurgitation using
      Cox regression models. Our primary exposure variable was SBP and our primary
      outcome was incident reports of mitral regurgitation, which were identified from
      hospital discharge reports or primary care records. Of the 5,553,984 patients in
      the CPRD that met our inclusion criteria, during the 10-year follow-up period,
      28,655 (0.52%) were diagnosed with mitral regurgitation and a further 1,262
      (0.02%) were diagnosed with mitral stenosis. SBP was continuously related to the
      risk of mitral regurgitation with no evidence of a nadir down to 115 mmHg (p <
      0.001). Each 20 mmHg increment in SBP was associated with a 26% higher risk of
      mitral regurgitation (hazard ratio [HR] 1.26; CI 1.23, 1.29). The observed
      association was partially mediated by diseases affecting the left ventricle
      during follow-up (myocardial infarction [MI], ischaemic heart disease [IHD],
      cardiomyopathy, and heart failure). However, the percentage of excess risk
      mediated (PERM) by these proximate causes of secondary mitral regurgitation was
      only 13% (CI 6.1%, 20%), and accounting for them had little effect on the long
      term association between SBP and mitral regurgitation (mediator-adjusted HR 1.22;
      CI 1.20, 1.25; p < 0.001). Associations were similar for each 10 mmHg increment
      in diastolic blood pressure (DBP) (p < 0.001) or each 15 mmHg increment in pulse
      pressure (PP) (p < 0.001). By contrast, there was no association between SBP and
      risk of mitral stenosis (HR per 20 mmHg higher SBP 1.03; CI 0.93, 1.14; p =
      0.58). These analyses are based on routinely collected data from health records
      which may be sensitive to measurement errors, and the observed associations may
      not be generalizable to less severe and subclinical cases of mitral
      regurgitation. CONCLUSIONS: Long-term exposure to elevated BP across its whole
      spectrum is associated with an increased risk of primary and secondary mitral
      regurgitation. These findings suggest that BP control may be of importance in the
      prevention of mitral regurgitation.

PMID- 29040270
TI  - Analysis of the interaction of Plexin-B1 and Plexin-B2 with Rnd family proteins.
AB  - The Rnd family of proteins, Rnd1, Rnd2 and Rnd3, are atypical Rho family GTPases,
      which bind to but do not hydrolyse GTP. They interact with plexins, which are
      receptors for semaphorins, and are hypothesised to regulate plexin signalling. We
      recently showed that each Rnd protein has a distinct profile of interaction with
      three plexins, Plexin-B1, Plexin-B2 and Plexin-B3, in mammalian cells, although
      it is unclear which region(s) of these plexins contribute to this specificity.
      Here we characterise the binary interactions of the Rnd proteins with the Rho
      binding domain (RBD) of Plexin-B1 and Plexin-B2 using biophysical approaches.
      Isothermal titration calorimetry (ITC) experiments for each of the Rnd proteins
      with Plexin-B1-RBD and Plexin-B2-RBD showed similar association constants for all
      six interactions, although Rnd1 displayed a small preference for Plexin-B1-RBD
      and Rnd3 for Plexin-B2-RBD. Furthermore, mutagenic analysis of Rnd3 suggested
      similarities in its interaction with both Plexin-B1-RBD and Plexin-B2-RBD. These
      results suggest that Rnd proteins do not have a clear-cut specificity for
      different Plexin-B-RBDs, possibly implying the contribution of additional regions
      of Plexin-B proteins in conferring functional substrate selection.

PMID- 29040271
TI  - Improving tuberculosis diagnosis: Better tests or better healthcare?
AB  - In a Perspective accompanying Sylvia and colleagues, Carlton Evans and colleagues
      discuss the challenge of squaring policies around tuberculosis diagnosis with the
      realities of clinical practice in small villages and low-resource settings.

PMID- 29040272
TI  - Woody lianas increase in dominance and maintain compositional integrity across an
      Amazonian dam-induced fragmented landscape.
AB  - Tropical forest fragmentation creates insular biological communities that undergo
      species loss and changes in community composition over time, due to area- and
      edge-effects. Woody lianas thrive in degraded and secondary forests, due to their
      competitive advantage over trees in these habitats. Lianas compete both directly
      and indirectly with trees, increasing tree mortality and turnover. Despite our
      growing understanding of liana-tree dynamics, we lack detailed knowledge of the
      assemblage-level responses of lianas themselves to fragmentation, particularly in
      evergreen tropical forests. We examine the responses of both sapling and mature
      liana communities to landscape-scale forest insularization induced by a mega
      hydroelectric dam in the Brazilian Amazon. Detailed field inventories were
      conducted on islands created during reservoir filling, and in nearby mainland
      continuous forest. We assess the relative importance of variables associated with
      habitat fragmentation such as area, isolation, surrounding forest cover, fire and
      wind disturbance, on liana community attributes including abundance, basal area,
      diversity, and composition. We also explore patterns of liana dominance relative
      to tree saplings and adults >=10 cm diameter at breast height. We find that 1)
      liana community composition remains remarkably similar across mainland continuous
      forest and islands, regardless of extreme area- and edge- effects and the loss of
      vertebrate dispersers in the latter; and 2) lianas are increasing in dominance
      relative to trees in the sapling layer in the most degraded islands, with both
      the amount of forest cover surrounding islands and fire disturbance history
      predicting liana dominance. Our data suggest that liana communities persist
      intact in isolated forests, regardless of extreme area- and edge-effects; while
      in contrast, tree communities simultaneously show evidence of increased turnover
      and supressed recruitment. These processes may lead to lianas becoming a dominant
      component of this dam-induced fragmented landscape in the future, due to their
      competitive advantage over trees in degraded forest habitats. Additional loss of
      tree biomass and diversity brought about through competition with lianas, and the
      concurrent loss of carbon storage, should be accounted for in impact assessments
      of future dam development.

PMID- 29040273
TI  - Schistosoma japonicum transmission risk maps at present and under climate change
      in mainland China.
AB  - BACKGROUND: The South-to-North Water Diversion (SNWD) project is designed to
      channel fresh water from the Yangtze River north to more industrialized parts of
      China. An important question is whether future climate change and dispersal via
      the SNWD may synergistically favor a northward expansion of species involved in
      hosting and transmitting schistosomiasis in China, specifically the intermediate
      host, Oncomelania hupensis. METHODOLOGY/ PRINCIPAL FINDINGS: In this study,
      climate spaces occupied by the four subspecies of O. hupensis (O. h. hupensis, O.
      h. robertsoni, O. h. guangxiensis and O. h. tangi) were estimated, and niche
      conservatism tested among each pair of subspecies. Fine-tuned Maxent (fMaxent)
      and ensemble models were used to anticipate potential distributions of O.
      hupensis under future climate change scenarios. We were largely unable to reject
      the null hypothesis that climatic niches are conserved among the four subspecies,
      so factors other than climate appear to account for the divergence of O. hupensis
      populations across mainland China. Both model approaches indicated increased
      suitability and range expansion in O. h. hupensis in the future; an eastward and
      northward shift in O. h. robertsioni and O. h. guangxiensis, respectively; and
      relative distributional stability in O. h. gangi. CONCLUSIONS/SIGNIFICANCE: The
      southern parts of the Central Route of SNWD will coincide with suitable areas for
      O. h. hupensis in 2050-2060; its suitable areas will also expand northward along
      the southern parts of the Eastern Route by 2080-2090. Our results call for
      rigorous monitoring and surveillance of schistosomiasis along the southern
      Central Route and Eastern Route of the SNWD in a future, warmer China.

PMID- 29040275
TI  - Nocturnal sleep mediates the relationship between morningness-eveningness
      preference and the sleep architecture of afternoon naps in university students.
AB  - The present study investigated the parameters of nocturnal sleep that mediate the
      relationship between morningness-eveningness preference and the sleep
      architecture of naps in university students. This study had a cross-sectional,
      descriptive correlational design. The sleep architecture of 52 students invited
      to take an afternoon nap in the laboratory was recorded. The morningness
      eveningness questionnaire (MEQ) was used to evaluate morningness-eveningness
      preference. An actigraph was used to collect students' nighttime sleep data in
      the week preceding the study. Polysomnography was used to measure the sleep
      architecture of the participants' naps. After adjustments for potential factors,
      although the MEQ did not directly correlate with the percentage of sleep stages
      in naps, the effects of the MEQ on the percentage of Stage 1 sleep, slow-wave
      sleep, and rapid eye movement sleep; sleep duration; and sleep efficiency of naps
      were mediated by the total sleep time in the preceding week. This preliminary
      study suggests that nap quality was affected by morningness-eveningness
      preference through the mediation of total nocturnal sleep time. Therefore, future
      studies should be carefully designed to consider nighttime sleep patterns when
      analyzing the effects of chronotypes on daytime sleep.

PMID- 29040274
TI  - A quadratically regularized functional canonical correlation analysis for
      identifying the global structure of pleiotropy with NGS data.
AB  - Investigating the pleiotropic effects of genetic variants can increase
      statistical power, provide important information to achieve deep understanding of
      the complex genetic structures of disease, and offer powerful tools for designing
      effective treatments with fewer side effects. However, the current multiple
      phenotype association analysis paradigm lacks breadth (number of phenotypes and
      genetic variants jointly analyzed at the same time) and depth (hierarchical
      structure of phenotype and genotypes). A key issue for high dimensional
      pleiotropic analysis is to effectively extract informative internal
      representation and features from high dimensional genotype and phenotype data. To
      explore correlation information of genetic variants, effectively reduce data
      dimensions, and overcome critical barriers in advancing the development of novel
      statistical methods and computational algorithms for genetic pleiotropic
      analysis, we proposed a new statistic method referred to as a quadratically
      regularized functional CCA (QRFCCA) for association analysis which combines three
      approaches: (1) quadratically regularized matrix factorization, (2) functional
      data analysis and (3) canonical correlation analysis (CCA). Large-scale
      simulations show that the QRFCCA has a much higher power than that of the ten
      competing statistics while retaining the appropriate type 1 errors. To further
      evaluate performance, the QRFCCA and ten other statistics are applied to the
      whole genome sequencing dataset from the TwinsUK study. We identify a total of 79
      genes with rare variants and 67 genes with common variants significantly
      associated with the 46 traits using QRFCCA. The results show that the QRFCCA
      substantially outperforms the ten other statistics.

PMID- 29040276
TI  - The impact of acute kidney injury on in-hospital mortality in acute ischemic
      stroke patients undergoing intravenous thrombolysis.
AB  - INTRODUCTION: Acute kidney injury (AKI) increases the risk of death in acute
      ischemic stroke (AIS) patients. Intravenous thrombolytic therapy (iv. rt-PA)
      seems to be the most effective treatment for AIS patients. The effects of AKI on
      iv. rt-PA treated AIS cases is less studied. Our paper addresses this issue.
      METHODS: 45 consecutive stroke patients treated with iv. rt-PA (median age = 64
      years; 29 male) and 59 age and sex matched controls not eligible for iv. rt-PA
      have been enrolled in our study. Subjects were followed-up until hospital release
      or death (median follow up time = 12 days). RESULTS: The prevalence of AKI did
      not differ between iv. rt-PA treated patients and controls (35.5% vs. 33.89%). In
      both groups, AKI was associated with increased in-hospital mortality: 50.0% vs.
      3.4% p<0.0001 (in the rt-PA treated), and 45% vs. 30.7% (in controls). AKI iv. rt
      PA treated patients had a significantly higher risk of in hospital mortality as
      compared to the no-AKI iv. rt-PA treated (HR = 15.2 (95%CI [1.87 to 124.24]; P =
      0.011). In a Cox-multivariate model, the presence of AKI after iv. rt-PA remained
      a significant factor (HR = 8.354; p = 0.041) influencing the in-hospital
      mortality even after correction for other confounding factors. The independent
      predictors for AKI were: decreased eGFR baseline and elevated serum levels of
      uric acid at admission, (the model explained 60.2% of the AKI development).
      CONCLUSIONS: The risk of AKI was increased in AIS patients. Thrombolysis itself
      did not increase the risk of AKI. In the iv. rt-PA patients, as compared to non
      AKI, those which developed AKI had a higher rate of in-hospital mortality. The
      baseline eGFR and the serum uric acid at admission were independent predictors
      for AKI development in the iv. rt-PA treated AIS patients.

PMID- 29040277
TI  - Personality and achievement along medical training: Evidence from a cross-lagged
      analysis.
AB  - INTRODUCTION: Evidence on personality traits change implies it should be studied
      as an outcome and not only as an explanatory effect. Therefore, we aimed to
      assess how personality and academic achievement sway each other. Three cohorts of
      medical students (n = 181) comprised of school leavers and graduates, completed
      NEO-FFI when admitted (baseline) and later on medical training (follow-up).
      Previous achievement was measured as mean scores on national school examinations,
      and academic achievement as medical course average. Causal relations were studied
      by cross-lagged analysis. RESULTS: Cross-sectional analysis at baseline showed
      differences between graduates and school leavers on personality, with graduates
      scoring lower on neuroticism (beta = -12.344, p<0.001), and higher on openness to
      experience (beta = 5.257, p<0.001), conscientiousness (beta = 2.345, p = 0.004,)
      and agreeableness (beta = 6.993, p<0.001). Longitudinal analyses indicated that
      personality traits and achievement tracked over time. Cross-lagged analysis found
      a positive significant association between academic achievement and neuroticism
      at baseline (beta = 0.031, p = 0.014) and with being a graduate student (beta =
      0.766, p = 0.006). After adjusting, no association was found between previous
      achievement and personality at follow-up. CONCLUSIONS: Some neuroticism may
      enhance medical academic achievement. The blurring of the initial differences
      between graduates and school leavers suggests a reasonable possibility of
      personality traits change along the medical course. Future research on medical
      selection processes cannot afford to ignore the influence of the medical school
      environment on personality traits change.

PMID- 29040278
TI  - PG-Metrics: A chemometric-based approach for classifying bacterial peptidoglycan
      data sets and uncovering their subjacent chemical variability.
AB  - Bacteria cells are protected from osmotic and environmental stresses by an
      exoskeleton-like polymeric structure called peptidoglycan (PG) or murein
      sacculus. This structure is fundamental for bacteria's viability and thus, the
      mechanisms underlying cell wall assembly and how it is modulated serve as targets
      for many of our most successful antibiotics. Therefore, it is now more important
      than ever to understand the genetics and structural chemistry of the bacterial
      cell walls in order to find new and effective methods of blocking it for the
      treatment of disease. In the last decades, liquid chromatography and mass
      spectrometry have been demonstrated to provide the required resolution and
      sensitivity to characterize the fine chemical structure of PG. However, the large
      volume of data sets that can be produced by these instruments today are difficult
      to handle without a proper data analysis workflow. Here, we present PG-metrics, a
      chemometric based pipeline that allows fast and easy classification of bacteria
      according to their muropeptide chromatographic profiles and identification of the
      subjacent PG chemical variability between e.g. bacterial species, growth
      conditions and, mutant libraries. The pipeline is successfully validated here
      using PG samples from different bacterial species and mutants in cell wall
      proteins. The obtained results clearly demonstrated that PG-metrics pipeline is a
      valuable bioanalytical tool that can lead us to cell wall classification and
      biomarker discovery.

PMID- 29040279
TI  - Social exclusion leads to attentional bias to emotional social information:
      Evidence from eye movement.
AB  - Social exclusion has many effects on individuals, including the increased need to
      belong and elevated sensitivity to social information. Using a self-reporting
      method, and an eye-tracking technique, this study explored people's need to
      belong and attentional bias towards the socio-emotional information (pictures of
      positive and negative facial expressions compared to those of emotionally-neutral
      expressions) after experiencing a brief episode of social exclusion. We found
      that: (1) socially-excluded individuals reported higher negative emotions, lower
      positive emotions, and stronger need to belong than those who were not socially
      excluded; (2) compared to a control condition, social exclusion caused a longer
      response time to probe dots after viewing positive or negative face images; (3)
      social exclusion resulted in a higher frequency ratio of first attentional
      fixation on both positive and negative emotional facial pictures (but not on the
      neutral pictures) than the control condition; (4) in the social exclusion
      condition, participants showed shorter first fixation latency and longer first
      fixation duration to positive pictures than neutral ones but this effect was not
      observed for negative pictures; (5) participants who experienced social exclusion
      also showed longer gazing duration on the positive pictures than those who did
      not; although group differences also existed for the negative pictures, the gaze
      duration bias from both groups showed no difference from chance. This study
      demonstrated the emotional response to social exclusion as well as characterising
      multiple eye-movement indicators of attentional bias after experiencing social
      exclusion.

PMID- 29040280
TI  - Quantitative analysis of neural tissues around the optic disc after panretinal
      photocoagulation in patients with diabetic retinopathy.
AB  - In this retrospective cross-sectional study, we quantitatively analyzed the
      tomographic features in the neural tissues around the optic disc in patients with
      diabetic retinopathy with and without panretinal photocoagulation. We analyzed
      206 eyes, comprising 33 normal eyes in subjects without diabetes (group I), 30
      eyes without diabetic retinopathy (group II), 66 eyes with non-proliferative
      diabetic retinopathy (group III), 45 eyes with panretinal photocoagulation (group
      IV), and 32 eyes with normal tension glaucoma (group V). Sequential images
      acquired using swept-source optical coherence tomography in three-dimensional
      mode were used to measure peripapillary retinal nerve fiber layer thickness,
      neuro-retinal rim thickness, anterior lamina cribrosa depth, prelaminar
      thickness, and thickness of the lamina cribrosa. The peripapillary retinal nerve
      fiber layer thickness and lamina cribrosa thickness were significantly thinner in
      group IV than in group III (p = 0.019 and p < 0.001). However, there was no
      significant difference in rim thickness, anterior lamina cribrosa depth, or
      prelaminar thickness between groups III and IV (p = 0.307, p = 0.877, and p =
      0.212). Multivariate analysis revealed that time since panretinal
      photocoagulation and thickness of the lamina cribrosa had a significant effect on
      peripapillary retinal nerve fiber layer thickness (p < 0.001 and p = 0.014). In
      group IV, there was a negative correlation between time elapsed since panretinal
      photocoagulation and peripapillary retinal nerve fiber layer thickness, rim
      thickness, and thickness of the lamina cribrosa (r = -0.765, r = -0.490, and r = 
      0.419), but no correlation with prelaminar thickness or anterior lamina cribrosa
      depth (r = 0.104 and r = -0.171). Panretinal photocoagulation may be related to
      thinning of the peripapillary retinal nerve fiber layer, rim thickness, and
      lamina cribrosa, but not prelaminar thickness or anterior lamina cribrosa depth.
      These features are different from the peripapillary features of eyes with typical
      normal tension glaucoma.

PMID- 29040281
TI  - Impaired anti-fibrotic effect of bone marrow-derived mesenchymal stem cell in a
      mouse model of pulmonary paracoccidioidomycosis.
AB  - Bone marrow-derived mesenchymal stem cells (BMMSCs) have been consider as a
      promising therapy in fibrotic diseases. Experimental models suggest that BMMSCs
      may be used as an alternative therapy to treat chemical- or physical-induced
      pulmonary fibrosis. We investigated the anti-fibrotic potential of BMMSCs in an
      experimental model of lung fibrosis by infection with Paracoccidioides
      brasiliensis. BMMSCs were isolated and purified from BALB/c mice using
      standardized methods. BALB/c male mice were inoculated by intranasal infection of
      1.5x106 P. brasiliensis yeasts. Then, 1x106 BMMSCs were administered intra venous
      at 8th week post-infection (p.i.). An additional group of mice was treated with
      itraconazole (ITC) two weeks before BMMSCs administration. Animals were
      sacrificed at 12th week p.i. Histopathological examination, fibrocytes counts,
      soluble collagen and fibrosis-related genes expression in lungs were evaluated.
      Additionally, human fibroblasts were treated with homogenized lung supernatants
      (HLS) to determine induction of collagen expression. Histological analysis showed
      an increase of granulomatous inflammatory areas in BMMSCs-treated mice. A
      significant increase of fibrocytes count, soluble collagen and collagen-3alpha1,
      TGF-beta3, MMP-8 and MMP-15 genes expression were also observed in those mice.
      Interestingly, when combined therapy BMMSCs/ITC was used there is a decrease of
      TIMP-1 and MMP-13 gene expression in infected mice. Finally, human fibroblasts
      stimulated with HLS from infected and BMMSCs-transplanted mice showed a higher
      expression of collagen I. In conclusion, our findings indicate that late infusion
      of BMMSCs into mice infected with P. brasiliensis does not have any anti-fibrotic
      effect; possibly because their interaction with the fungus promotes collagen
      expression and tissue remodeling.

PMID- 29040282
TI  - Colorectal carcinoma tumour budding and podia formation in the xenograft
      microenvironment.
AB  - Tumour budding and podia formation are well-appreciated in surgical pathology as
      an aggressive invasion phenotype of colorectal carcinoma cells that is attained
      in the microenvironment of the invasive margin. In this study, we addressed how
      tumour budding and podia formation feature in xenografts. Primary colorectal
      carcinomas (N = 44) of various molecular types (sporadic standard type, high
      degree microsatellite-unstable, CpG island methylator phenotype) were
      transplanted subcutaneously into T and B cell-deficient NSG mice, making possible
      immunohistochemistry with routine surgical pathology antibodies. Tumor budding
      and podia formation were both appreciably present in the xenografts. Quantitative
      evaluations of cytokeratin immunostains of primaries and their corresponding
      xenografts showed a reduction of tumour buds in the xenografts. Furthermore, in
      xenografts tumour cells were completely negative by pSTAT3 immunohistochemistry,
      indicating absence of cytokine/chemokine signalling, but nuclear beta-catenin and
      SMAD4 immunostainings as read-out of wnt and BMP pathway activation,
      respectively, were maintained. Carcinoma cells in most xenografts retained
      immunostaining of at least some nuclei by immunohistochemistry with antibodies
      against pERK1/2. K-ras/B-raf mutational status did not correlate with tumour
      budding or podia formation in the xenografts. Our results indicate that tumour
      budding and podia formation can be modelled by xenografting, and in NSG mice it
      can be studied with the same immunohistochemical methods as used for primaries in
      surgical pathology. Dysregulation of wnt and BMP signalling appears to be
      transferred into the xenograft microenvironment, but not cytokine/chemokine
      signalling.

PMID- 29040283
TI  - Non-linear Min protein interactions generate harmonics that signal mid-cell
      division in Escherichia coli.
AB  - The Min protein system creates a dynamic spatial pattern in Escherichia coli
      cells where the proteins MinD and MinE oscillate from pole to pole. MinD
      positions MinC, an inhibitor of FtsZ ring formation, contributing to the mid-cell
      localization of cell division. In this paper, Fourier analysis is used to
      decompose experimental and model MinD spatial distributions into time-dependent
      harmonic components. In both experiment and model, the second harmonic component
      is responsible for producing a mid-cell minimum in MinD concentration. The
      features of this harmonic are robust in both experiment and model. Fourier
      analysis reveals a close correspondence between the time-dependent behaviour of
      the harmonic components in the experimental data and model. Given this, each
      molecular species in the model was analysed individually. This analysis revealed
      that membrane-bound MinD dimer shows the mid-cell minimum with the highest
      contrast when averaged over time, carrying the strongest signal for positioning
      the cell division ring. This concurs with previous data showing that the MinD
      dimer binds to MinC inhibiting FtsZ ring formation. These results show that non
      linear interactions of Min proteins are essential for producing the mid-cell
      positioning signal via the generation of second-order harmonic components in the
      time-dependent spatial protein distribution.

PMID- 29040284
TI  - The prevalence and clinical manifestation of hereditary thrombophilia in Korean
      patients with unprovoked venous thromboembolisms.
AB  - BACKGROUND: Hereditary thrombophilia (HT) is a genetic predisposition to
      thrombosis. Asian mutation spectrum of HT is different from Western ones. We
      investigated the incidence and clinical characteristics of HT in Korean patients
      with unprovoked venous thromboembolism (VTE). METHODS: Among 369 consecutive
      patients with thromboembolic event who underwent thrombophilia tests, we enrolled
      222 patients diagnosed with unprovoked VTE. The presence of HT was confirmed by
      DNA sequencing of the genes that cause deficits in natural anticoagulants (NAs).
      Median follow-up duration was 40+/-38 months. RESULTS: Among the 222 patients
      with unprovoked VTE, 66 (29.7%) demonstrated decreased NA level, and 33 (14.9%)
      were finally confirmed to have HT in a genetic molecular test. Antithrombin III
      deficiency (6.3%) was most frequently detected, followed by protein C deficiency
      (5.4%), protein S deficiency (1.8%), and dysplasminogenemia (1.4%). The HT group
      was significantly younger (37 [32-50] vs. 52 [43-65] years; P < 0.001) and had a
      higher proportion of male (69.7% vs. 47%; P = 0.013), more previous VTE events
      (57.6% vs. 31.7%; P = 0.004), and a greater family history of VTE (43.8% vs.
      1.9%; P < 0.001) than the non-HT group. Age <45 years and a family history of VTE
      were independent predictors for unprovoked VTE with HT (odds ratio, 9.435 [2.45
      36.35]; P = 0.001 and 92.667 [14.95-574.29]; P < 0.001). CONCLUSIONS: About 15%
      of patients with unprovoked VTE had HT. A positive family history of VTE and age
      <45 years were independent predictors for unprovoked VTE caused by HT.

PMID- 29040285
TI  - De novo pyrimidine synthesis is necessary for intestinal colonization of
      Salmonella Typhimurium in chicks.
AB  - pyrE (STM3733) encodes orotate phosphoribosyltransferase (OPRTase; EC 2.4.2.10),
      the fifth enzyme of the de novo pyrimidine biosynthetic pathway. We identified a
      DeltapyrE mutant as under selection in screening of a Salmonella mutant library
      in 4-day old chicks. Here, we confirm that a DeltapyrE mutant colonizes 4-day old
      chicks poorly in competitive infection with isogenic wild type, and that the
      ability of this mutant to colonize chicks could be restored by providing a copy
      of pyrE in trans. We further show that our DeltapyrE mutant grows poorly in
      nutrient poor conditions in vitro, and that the ability of this mutant to grow is
      restored, both in vitro and in chicks, when precursors to the pyrimidine salvage
      pathway were provided. This finding suggests that the environment in the chick
      intestine during our infections lacks sufficient precursors of the pyrimidine
      salvage pathway to support Salmonella growth. Finally, we show that the
      colonization defect of a DeltapyrE mutant during infection occurs in to chicks,
      but not in CBA/J mice or ligated ileal loops in calves. Our data suggest that de
      novo pyrimidine synthesis is necessary for colonization of Salmonella Typhimurium
      in the chick, and that the salvage pathway is not used in this niche.

PMID- 29040287
TI  - Antimicrobial activity of carbon monoxide-releasing molecule [Mn(CO)3(tpa
      kappa3N)]Br versus multidrug-resistant isolates of Avian Pathogenic Escherichia
      coli and its synergy with colistin.
AB  - Antimicrobial resistance is a growing global concern in human and veterinary
      medicine, with an ever-increasing void in the arsenal of clinicians. Novel
      classes of compounds including carbon monoxoide-releasing molecules (CORMs), for
      example the light-activated metal complex [Mn(CO)3(tpa-kappa3N)]Br, could be used
      as alternatives/to supplement traditional antibacterials. Avian pathogenic
      Escherichia coli (APEC) represent a large reservoir of antibiotic resistance and
      can cause serious clinical disease in poultry, with potential as zoonotic
      pathogens, due to shared serotypes and virulence factors with human pathogenic E.
      coli. The in vitro activity of [Mn(CO)3(tpa-kappa3N)]Br against multidrug
      resistant APECs was assessed via broth microtitre dilution assays and synergy
      testing with colistin performed using checkerboard and time-kill assays. In vivo
      antibacterial activity of [Mn(CO)3(tpa-kappa3N)]Br alone and in combination with
      colistin was determined using the Galleria mellonella wax moth larvae model.
      Animals were monitored for life/death, melanisation and bacterial numbers
      enumerated from larval haemolymph. In vitro testing produced relatively high
      [Mn(CO)3(tpa-kappa3N)]Br minimum inhibitory concentrations (MICs) of 1024 mg/L.
      However, its activity was significantly increased with the addition of colistin,
      bringing MICs down to <=32 mg/L. This synergy was confirmed in time-kill assays.
      In vivo assays showed that the combination of [Mn(CO)3(tpa-kappa3N)]Br with
      colistin produced superior bacterial killing and significantly increased larval
      survival. In both in vitro and in vivo assays light activation was not required
      for antibacterial activity. This data supports further evaluation of [Mn(CO)3(tpa
      kappa3N)]Br as a potential agent for treatment of systemic infections in humans
      and animals, when used with permeabilising agents such as colistin.

PMID- 29040286
TI  - Human babesiosis: Indication of a molecular mimicry between thrombospondin
      domains from a novel Babesia microti BmP53 protein and host platelets molecules.
AB  - Human babesiosis is caused by the apicomplexan parasite Babesia microti, which is
      of major public health concern in the United States and elsewhere, resulting in
      malaise and fatigue, followed by a fever and hemolytic anemia. In this paper we
      focus on the characterization of a novel B. microti thrombospondin domain (TSP1)
      containing protein (BmP53) from the new annotation of the B. microti genome
      (locus 'BmR1_04g09041'). This novel protein (BmP53) had a single TSP1 and a
      transmembrane domain, with a short cytoplasmic tail containing a sub-terminal
      glutamine residue, but no signal peptide and Von Willebrand factor type A domains
      (VWA), which are found in classical thrombospondin-related adhesive proteins
      (TRAP). Co-localization assays of BmP53 and Babesia microti secreted antigen 1
      (BmSA1) suggested that BmP53 might be a non-secretory membranous protein.
      Molecular mimicry between the TSP1 domain from BmP53 and host platelets molecules
      was indicated through different measures of sequence homology, phylogenetic
      analysis, 3D structure and shared epitopes. Indeed, hamster isolated platelets
      cross-reacted with mouse anti-BmP53-TSP1. Molecular mimicry are used to help
      parasites to escape immune defenses, resulting in immune evasion or autoimmunity.
      Furthermore, specific host reactivity was also detected against the TSP1-free
      part of BmP53 in infected hamster sera. In conclusion, the TSP1 domain mimicry
      might help in studying the mechanisms of parasite-induced thrombocytopenia, with
      the TSP1-free truncate of the protein representing a potential safe candidate for
      future vaccine studies.

PMID- 29040288
TI  - Music viewed by its entropy content: A novel window for comparative analysis.
AB  - Polyphonic music files were analyzed using the set of symbols that produced the
      Minimal Entropy Description, which we call the Fundamental Scale. This allowed us
      to create a novel space to represent music pieces by developing: (a) a method to
      adjust a textual description from its original scale of observation to an
      arbitrarily selected scale, (b) a method to model the structure of any textual
      description based on the shape of the symbol frequency profiles, and (c) the
      concept of higher order entropy as the entropy associated with the deviations of
      a frequency-ranked symbol profile from a perfect Zipfian profile. We call this
      diversity index the '2nd Order Entropy'. Applying these methods to a variety of
      musical pieces showed how the space of 'symbolic specific diversity-entropy' and
      that of '2nd order entropy' captures characteristics that are unique to each
      music type, style, composer and genre. Some clustering of these properties around
      each musical category is shown. These methods allow us to visualize a historic
      trajectory of academic music across this space, from medieval to contemporary
      academic music. We show that the description of musical structures using entropy,
      symbol frequency profiles and specific symbolic diversity allows us to
      characterize traditional and popular expressions of music. These classification
      techniques promise to be useful in other disciplines for pattern recognition and
      machine learning.

PMID- 29040290
TI  - Complex Conjugated certificateless-based signcryption with differential
      integrated factor for secured message communication in mobile network.
AB  - Certificateless-based signcryption overcomes inherent shortcomings in traditional
      Public Key Infrastructure (PKI) and Key Escrow problem. It imparts efficient
      methods to design PKIs with public verifiability and cipher text authenticity
      with minimum dependency. As a classic primitive in public key cryptography,
      signcryption performs validity of cipher text without decryption by combining
      authentication, confidentiality, public verifiability and cipher text
      authenticity much more efficiently than the traditional approach. In this paper,
      we first define a security model for certificateless-based signcryption called,
      Complex Conjugate Differential Integrated Factor (CC-DIF) scheme by introducing
      complex conjugates through introduction of the security parameter and improving
      secured message distribution rate. However, both partial private key and secret
      value changes with respect to time. To overcome this weakness, a new
      certificateless-based signcryption scheme is proposed by setting the private key
      through Differential (Diff) Equation using an Integration Factor (DiffEIF),
      minimizing computational cost and communication overhead. The scheme is therefore
      said to be proven secure (i.e. improving the secured message distributing rate)
      against certificateless access control and signcryption-based scheme. In
      addition, compared with the three other existing schemes, the CC-DIF scheme has
      the least computational cost and communication overhead for secured message
      communication in mobile network.

PMID- 29040289
TI  - Sole vibration improves locomotion through the recovery of joint movements in a
      mouse cast model.
AB  - We investigated the effects of a vibratory stimulus on the plantar surface of the
      hind limb for motor, sensory, and locomotive function using a mouse cast model.
      The right knee joint of C57BL/6 male mice (7 weeks, 20 g, n = 31) was flexed with
      aluminum splint and tape for 6 weeks. These mice were randomly divided into 2
      groups (control group, n = 11 and vibration group, n = 12). The mice in the
      vibration group received vibration on the sole of the ankle for 15 minutes per
      day, 5 days per week. After the knee joint cast was removed, we measured the
      range of motion (ROM) of both knee and ankle joints and the sensory threshold of
      the sole. Further, both walking and swimming movements were analyzed with a
      digital video. The sole vibration did not affect the passive ROM of the knee
      joint and sensory threshold after cast removal. However, it increased the ankle
      dorsiflexion range and improved free walking, swimming, and active movement of
      the knee joint. In conclusion, we show that the vibration recovered both walking
      and swimming movements, which resulted from improvements in both the passive
      ankle dorsiflexion and active knee movement.

PMID- 29040291
TI  - Trade-off between jerk and time headway as an indicator of driving style.
AB  - Variation in longitudinal control in driving has been discussed in both traffic
      psychology and transportation engineering. Traffic psychologists have concerned
      themselves with "driving style", a habitual form of behavior marked by it's
      stability, and its basis in psychological traits. Those working in traffic
      microsimulation have searched for quantitative ways to represent different driver
      car systems in car following models. There has been unfortunately little overlap
      or theoretical consistency between these literatures. Here, we investigated
      relationships between directly observable measures (time headway, acceleration
      and jerk) in a simulated driving task where the driving context, vehicle and
      environment were controlled. We found individual differences in the way a trade
      off was made between close but jerky vs. far and smooth following behavior. We
      call these "intensive" and "calm" driving, and suggest this trade-off can serve
      as an indicator of a possible latent factor underlying driving style. We posit
      that pursuing such latent factors for driving style may have implications for
      modelling driver heterogeneity across various domains in traffic simulation.

PMID- 29040292
TI  - Intereye comparison of ocular factors in normal tension glaucoma with asymmetric
      visual field loss in Korean population.
AB  - PURPOSE: To identify ocular parameters corresponding to asymmetric visual field
      (VF) loss in normal tension glaucoma (NTG) through intereye comparisons. PATIENTS
      AND METHODS: Medical records of NTG patients with asymmetric and symmetric VF
      losses were retrospectively reviewed. The criterion for asymmetry in VF was 6 dB
      difference of mean deviation. Refractive error, intraocular pressure (IOP),
      central corneal thickness, ovality index, and peripapillary atrophy (PPA)/disc
      area ratio were obtained from each patient. Intereye comparison was performed for
      asymmetric group, symmetric group, and myopic and nonmyopic asymmetric subgroups.
      RESULTS: We included 155 patients; 110 patients in asymmetric group and 45
      patients in symmetric group. In intereye comparison for total asymmetric group,
      refractive error (P = 0.006), initial IOP (P = 0.001), ovality index (P = 0.008),
      and PPA (P < 0.001) were significantly asymmetric. For myopic subgroup,
      refractive error (P = 0.004), ovality index (P = 0.001), and PPA (P = 0.003) were
      significant factors. For nonmyopic subgroup, initial IOP (P = 0.003) and PPA (P =
      0.007) were significant factors. Symmetric group showed no significant difference
      between the eyes. Multivariate analysis demonstrated that refractive error (P =
      0.002) and PPA (P = 0.028) were significant factors in myopic subgroup, and
      initial IOP (P = 0.022) and PPA (P = 0.002) were significant factors in nonmyopic
      subgroup. CONCLUSIONS: In this intereye comparison, the more myopic eye in myopic
      NTG patient, and the more pressured eye in nonmyopic NTG patient demonstrated
      more severe VF loss. Myopic and nonmyopic patients may follow different
      pathophysiologic processes. Discriminative attentions should be paid to NTG
      patients by subtypes.

PMID- 29040293
TI  - Mapping of important taxonomic and productivity traits using genic and non-genic
      transposable element markers in peanut (Arachis hypogaea L.).
AB  - A mapping population of recombinant inbred lines (RILs) derived from TMV 2 and
      its mutant, TMV 2-NLM was employed for mapping important taxonomic and
      productivity traits using genic and non-genic transposable element markers in
      peanut. Single nucleotide polymorphism and copy number variation using RAD
      Sequencing data indicated very limited polymorphism between TMV 2 and TMV 2-NLM.
      But phenotypically they differed significantly for many taxonomic and
      productivity traits. Also, the RIL population showed significant variation for a
      few additional agronomic traits. A genetic linkage map of 1,205.66 cM was
      constructed using 91 genic and non-genic Arachis hypogaea transposable element
      (AhTE) markers. Using single marker analysis and QTL analysis, the markers with
      high phenotypic variance explained (PVE) were identified for branching pattern
      (32.3%), number of primary and secondary branches (19.9% and 28.4%,
      respectively), protein content (26.4%), days to 50% flowering (22.0%), content of
      oleic acid (15.1%), test weight (13.6%) and pod width (12.0%). Three genic
      markers (AhTE0357, AhTE0391, AhTE0025) with Arachis hypogaea miniature inverted
      repeat transposable element (AhMITE1) activity in the genes Araip.TG1BL (B02
      chromosome), Aradu.7N61X (A09 chromosome) and Aradu.7065G (A07 chromosome),
      respectively showed strong linkage with these taxonomic, productivity and quality
      traits. Since TMV 2 and TMV 2-NLM differed subtly at DNA level, the background
      noise in detecting the marker-trait associations was minimum; therefore, the
      markers identified in this study for the taxonomic and productivity traits may be
      significant and useful in peanut molecular breeding.

PMID- 29040294
TI  - Towards social autonomous vehicles: Efficient collision avoidance scheme using
      Richardson's arms race model.
AB  - This paper presents the concept of a social autonomous agent to conceptualize
      such Autonomous Vehicles (AVs), which interacts with other AVs using social
      manners similar to human behavior. The presented AVs also have the capability of
      predicting intentions, i.e. mentalizing and copying the actions of each other,
      i.e. mirroring. Exploratory Agent Based Modeling (EABM) level of the Cognitive
      Agent Based Computing (CABC) framework has been utilized to design the proposed
      social agent. Furthermore, to emulate the functionality of mentalizing and
      mirroring modules of proposed social agent, a tailored mathematical model of the
      Richardson's arms race model has also been presented. The performance of the
      proposed social agent has been validated at two levels-firstly it has been
      simulated using NetLogo, a standard agent-based modeling tool and also, at a
      practical level using a prototype AV. The simulation results have confirmed that
      the proposed social agent-based collision avoidance strategy is 78.52% more
      efficient than Random walk based collision avoidance strategy in congested flock
      like topologies. Whereas practical results have confirmed that the proposed
      scheme can avoid rear end and lateral collisions with the efficiency of 99.876%
      as compared with the IEEE 802.11n-based existing state of the art mirroring
      neuron-based collision avoidance scheme.

PMID- 29040296
TI  - Constructing regional climate networks in the Amazonia during recent drought
      events.
AB  - Climate networks are powerful approaches to disclose tele-connections in climate
      systems and to predict severe climate events. Here we construct regional climate
      networks from precipitation data in the Amazonian region and focus on network
      properties under the recent drought events in 2005 and 2010. Both the networks of
      the entire Amazon region and the extreme networks resulted from locations
      severely affected by drought events suggest that network characteristics show
      slight difference between the two drought events. Based on network degrees of
      extreme drought events and that without drought conditions, we identify regions
      of interest that are correlated to longer expected drought period length.
      Moreover, we show that the spatial correlation length to the regions of interest
      decayed much faster in 2010 than in 2005, which is because of the dual roles
      played by both the Pacific and Atlantic oceans. The results suggest that hub
      nodes in the regional climate network of Amazonia have fewer long-range
      connections when more severe drought conditions appeared in 2010 than that in
      2005.

PMID- 29040295
TI  - Hydrophobic residues are critical for the helix-forming, hemolytic and
      bactericidal activities of amphipathic antimicrobial peptide TP4.
AB  - Antimicrobial peptides are important components of the host innate defense
      mechanism against invading pathogens, especially for drug-resistant bacteria. In
      addition to bactericidal activity, the 25 residue peptide TP4 isolated from Nile
      tilapia also stimulates cell proliferation and regulates the innate immune system
      in mice. In this report, TP4 hyperpolarized and depolarized the membrane
      potential of Pseudomonas aeruginosa at sub-lethal and lethal concentrations. It
      also inhibited and eradicated biofilm formation. The in vitro binding of TP4 to
      bacterial outer membrane target protein, OprI, was markedly enhanced by a
      membrane-like surfactant sarkosyl and lipopolysaccharide, which converted TP4
      into an alpha-helix. The solution structure of TP4 in dodecylphosphocholine was
      solved by NMR analyses. It contained a typical alpha-helix at residues Phe10
      Arg22 and a distorted helical segment at Ile6-Phe10, as well as a hydrophobic
      core at the N-terminus and a cationic patch at the C-terminus. Residues Ile16,
      Leu19 and Ile20 in the hydrophobic face of the main helix were critical for the
      integrity of amphipathic structure, other hydrophobic residues played important
      roles in hemolytic and bactericidal activities. A model for the assembly of
      helical TP4 embedded in sarkosyl vesicle is proposed. This study may provide
      valuable insight for engineering AMPs to have potent bactericidal activity but
      low hemolytic activity.

PMID- 29040297
TI  - Decreased NK cell immunity in kidney transplant recipients late post-transplant
      and increased NK-cell immunity in patients with recurrent miscarriage.
AB  - BACKGROUND: There is evidence that NK-cell reactivity might affect graft outcome
      in transplant recipients and pregnancy in women. METHOD: NK-cell subsets were
      determined in whole blood using eight-colour-fluorescence flow cytometry in
      patients before and after renal transplantation, patients with recurrent
      miscarriage (RM) and healthy controls (HC). RESULTS: Patients late post
      transplant (late-Tx) with functioning renal transplants showed abnormally low
      CD56dimCD16+ NK-cells containing both perforin and granzyme (vs HC p = 0.021)
      whereas RM patients exhibited abnormally high numbers of these cells (vs HC p =
      0.043). CD56dimCD16+perforin+granzyme+ NK-cell counts were strikingly different
      between the two patient groups (p<0.001). In addition, recipients late-Tx showed
      abnormally low CD8+ NK-cells (vs HC p<0.001) in contrast to RM patients who
      showed an abnormal increase (vs HC p = 0.008). CD8+ NK-cell counts were strongly
      different between the two patient groups (p<0.001). Higher
      perforin+granzyme+CD56dimCD16+ and CD8+ NK-cells were associated with impaired
      graft function (p = 0.044, p = 0.032). After in-vitro stimulation, CD56dimCD16+
      and CD56brightCD16dim/- NK-cells showed strong upregulation of CD107a and IFNy,
      whereas the content of perforin decreased dramatically as a consequence of
      perforin release. Recipients late post-Tx showed less in-vitro perforin release
      (= less cytotoxicity) than HC (p = 0.037) and lower perforin release was
      associated with good graft function (r = 0.738, p = 0.037). Notably, we observed
      strong in-vitro perforin release in 2 of 6 investigated RM patients. When
      circulating IL10+CD56bright NK-cells were analyzed, female recipients late post
      Tx (n = 9) showed significantly higher relative and absolute cell numbers than RM
      patients (p = 0.002 and p = 0.018, respectively); and high relative and absolute
      IL10+CD56bright NK-cell numbers in transplant recipients were associated with low
      serum creatinine (p = 0.004 and p = 0.012) and high glomerular filtration rate (p
      = 0.011 and p = 0.002, respectively). Female recipients late post-Tx exhibited
      similar absolute but higher relative numbers of IL10+IFNy- NK-cells than RM
      patients (p>0.05 and p = 0.016, respectively). CONCLUSION: NK-cells with lower
      cytotoxicity and immunoregulatory function might contribute to good long-term
      graft outcome, whereas circulating NK-cells with normal or even increased
      cytotoxicity and less immunoregulatory capacity are observed in patients with RM.

PMID- 29040298
TI  - Relative mobility of the pelvis and spine during trunk axial rotation in chronic
      low back pain patients: A case-control study.
AB  - BACKGROUND: Trunk axial rotation is a risk factor for chronic low back pain
      (CLBP). The characteristics of rotational mobility in the pelvis and spine among
      CLBP patients are not fully understood. PURPOSE: The purpose of this study was to
      examine three-dimensional kinematic changes, and to compare the differences of
      rotational mobility and coupled motion, in patients with and without CLBP.
      METHODS: Fifteen patients with CLBP and 15 age and sex matched healthy subjects
      participated in this study. Each subject performed trunk rotation to maximum
      range of motion (ROM) in a standing position. The kinematics data was collected
      using a three-dimensional motion analysis system. The outcomes measured were the
      rotational ROM and the spine/pelvis ratio (SPR) in transvers plane at both
      maximum and 50% rotation position. The coupled angles in sagittal and frontal
      planes were also measured. RESULTS: No significant differences in rotational ROM
      of the thorax, pelvis, and spine were observed between two groups at maximum
      rotation position. However, there was a significant interaction between groups
      and rotational ROM of pelvis and spine (F = 4.57, p = 0.04), and the SPR in CLBP
      patients was significantly greater than that of the healthy subjects (CLBP; 0.50
      +/- 0.10 Control; 0.41 +/- 0.12, p = 0.04). The results at 50% rotation position
      were similar to that at maximum rotation. This indicates a relative increase in
      spinal rotation in the CLBP patients during trunk rotation. Moreover, the CLBP
      patients exhibited a significantly higher anterior tilt of the pelvis and
      extension of the spine in the sagittal plane coupled with rotation. CONCLUSIONS:
      CLBP patients had relative hyper rotational mobility of the spine as well as
      excessive spinal extension coupled with trunk rotation. These results suggest
      that uncoordinated trunk rotation might be a functional failure associated with
      CLBP.

PMID- 29040299
TI  - Comparison of capecitabine and oxaliplatin with S-1 as adjuvant chemotherapy in
      stage III gastric cancer after D2 gastrectomy.
AB  - AIM: To compare capecitabine and oxaliplatin (XELOX) with S-1 as adjuvant
      chemotherapy in stage III gastric cancer after D2 gastrectomy. METHODS: Clinical
      data from 206 patients who received XELOX or S-1 regimens as adjuvant
      chemotherapy in stage III gastric cancer were collected. Patients were divided
      into 2 groups according to regimen; the groups were XELOX (n = 114) and S-1
      monotherapy (n = 92). RESULTS: 3-year disease-free survival (DFS) was higher in
      the S-1 group than in the XELOX group (66.6% vs 59.1%; p = 0.636). 3-year overall
      survival (OS) was 75.6% in the S-1 group and 69.6% in the XELOX group (p =
      0.495). But, the difference was not statistically significant. Especially, for
      patients with stage IIIC disease, 3-year overall survival was 55.2% in the XELOX
      group and 39.0% in the S-1 group (hazard ratio, HR 0.50, 95% confidence interval,
      CI 0.23-1.10; p = 0.075). In multivariate analysis, N stage (HR, 5.639; 95% CI,
      1.297-24.522; p = 0.021) and cycle completion as planned (HR, 5.734; 95% CI,
      3.007-10.936; p<0.001) were independent predictors of overall survival.
      CONCLUSION: Adjuvant XELOX and S-1 regimen did not prove anything superior for
      stage III gastric cancer in this study. But, XELOX had a tendency to be superior
      to S-1 in stage IIIC gastric cancer after D2 gastrectomy although the difference
      was not statistically significant. N stage and cycle completion as planned were
      prognostic factors.

PMID- 29040300
TI  - Risk-factors for nodular hyperplasia of parathyroid glands in sHPT patients.
AB  - INTRODUCTION: Nodular hyperplasia of parathyroid glands (PG) is the most probable
      cause of medical treatment failure in secondary hyperparathyroidism (sHPT). This
      prospective cohort study is located at the interface of medical and surgical
      consideration of sHPT treatment options and identifies risk-factors for nodular
      hyperplasia of PG. MATERIAL AND METHODS: One-hundred-eight resected PG of 27
      patients with a broad spectrum of sHPT severity were classified according to the
      degree of hyperplasia by histopathology. Twenty routinely gathered parameters
      from medical history, ultrasound findings of PG and laboratory results were
      analyzed for their influence on nodular hyperplasia of PG by risk-adjusted
      multivariable binary regression. A prognostic model for non-invasive assessment
      of PG was developed and used to weight the individual impact of identified risk
      factors on the probability of nodular hyperplasia of single PG. RESULTS:
      Independent risk-factors for nodular hyperplasia of single PG were duration of
      dialysis in years, PG volume in mm3 determined by ultrasound and serum level of
      parathyroid hormone in pg/mL. Multivariable analyses computed a model with an
      Area Under the Receiver Operative Curve of 0.857 (95%-CI:0.773-0.941) when
      predicting nodular hyperplasia of PG. Theoretical assessment of risk-factor
      interaction revealed that the duration of dialysis had the strongest influence on
      the probability of nodular hyperplasia of single PG. CONCLUSIONS: The three
      identified risk-factors (duration of dialysis, PG volume determined by ultrasound
      and serum level of parathyroid hormone) can be easily gathered in daily routine
      and could be used to non-invasively assess the probability of nodular hyperplasia
      of PG. This assessment would benefit from periodically collected data sets of PG
      changes during the course of sHPT, so that the choice of medical or surgical sHPT
      treatment could be adjusted more to the naturally changing type of histological
      PG lesion on an individually adopted basis in the future.

PMID- 29040302
TI  - An investigation of perceived vehicle speed from a driver's perspective.
AB  - PURPOSE: Speed estimation of drivers' own vehicles and other vehicles on the road
      is an important task for drivers and is also crucial to the roadway safety. The
      objective of the study was to examine the effects of multiple factors such as
      image scale, speed, road type, driving experience, and gender on the speed
      perception of drivers' own vehicles. METHODS: Thirty participants consisted of 17
      males and 13 females, including 13 without driving experience. All participants
      estimated the driving speed of 192 5-second video clips, which were selected from
      naturalistic driving recordings. The recorded driving speeds were evenly
      distributed across the entire range from 5mph to 65mph. Half of the selected
      video clips were recorded on wide roads and another half were recorded on
      comparatively narrow roads. Video clips were played on a large screen, with each
      clip shown in one of 4 image scales (100%, 75%, 50%, and 38% of the actual field
      of view in the real world). RESULTS: Speed estimates were most accurate for the
      smallest image size (38% of the actual field of view). As the image size
      increased, the driving speed was increasingly underestimated. Participants with
      driving experience accurately estimated the driving speed on both wide and narrow
      roads whereas those without driving experience had greater underestimates on
      wider roads. Speeds were most accurately estimated within the range 25-35mph, but
      the speeds slower than the range tend to be overestimated and the speeds faster
      than the range are more likely to be underestimated. While males and females
      showed the same pattern across speed groups, females have greater estimation
      errors at the highest and lowest speed groups. Participants without driving
      experience showed increasing underestimation of speed as driving speed increased
      whereas participants with driving experience primarily underestimated the highest
      speeds. CONCLUSIONS: The present study shows the effect of multidimensional
      influential factors on perceived vehicle speed from drivers' perspective. The
      results also have implications for driving simulation scenario design, driving
      simulator setup, and the assessment of speed control in simulated and
      naturalistic environments.

PMID- 29040301
TI  - Surveying predictors of late-life longitudinal change in daily activity energy
      expenditure.
AB  - BACKGROUND: Total daily energy expenditure (TEE) is composed of resting metabolic
      rate (RMR), post-prandial thermogenesis and activity energy expenditure (AEE).
      Higher AEE is strongly associated with lower mortality and physical limitations
      among older adults, but factors that predict changes in AEE in septu and
      octogenarians are not clearly understood. OBJECTIVE: To identify factors
      associated with late-life longitudinal change in AEE. DESIGN: Energy expenditure
      was re-assessed in 83 participants (average age at baseline, 74.4+/-3.2 years)-an
      average of 7.5+/-0.54 years since the baseline measure. RMR was measured using
      indirect calorimetry and the thermic effect of meals was estimated at 10% of TEE.
      AEE was calculated as: TEE(0.9)-RMR. Participants were categorized into two
      groups according to the estimated day-to-day precision of the doubly-labeled
      water technique. Those who were within 10% or increased relative to their initial
      AEE measurement were categorized as having preserved AEE. Participants who
      declined greater than 10% of their initial measurement were categorized as having
      reduced AEE. A variety of socio-demographic, functional and mental factors, body
      composition, community and personal behaviors, blood measurements and health
      conditions were evaluated between groups at baseline and changes during follow
      up. RESULTS: Daily AEE declined 106.61+/-293.25 kcal, which equated to a 14.63+/
      40.57 kcal/d decrease per year. Fifty-nine percent (n = 49) preserved their AEE
      and 41% (n = 34) declined. Those who demonstrated a decline in AEE were older,
      had lower walking speed at baseline and showed a higher lean mass loss during
      follow up. Otherwise, groups were similar for socio-demographic characteristics,
      body composition, mental and physical function, health conditions and community
      and personal behaviors at baseline and change in these factors during follow-up.
      CONCLUSIONS: This study demonstrates that AEE declines through the 8th decade of
      life and is associated with age, lower walking speed at baseline and lean mass
      loss. Additionally, there are a significant number of individuals who appear to
      be resilient to these declines despite having health events that are expected to
      have a negative impact on their physical activity.

PMID- 29040303
TI  - Continuing professional development for medical, nursing, and midwifery cadres in
      Malawi, Tanzania and South Africa: A qualitative evaluation.
AB  - BACKGROUND: As innovations in the prevention and treatment of HIV and TB advance,
      continuing professional development (CPD) of health care workers (HCWs) remains a
      high priority, particularly in sub-Saharan Africa where dual TB/HIV epidemics are
      compounded by severe HCW shortages. There is further need to examine CPD programs
      to identify challenges and effective solutions to strengthen HIV/TB-related CPD.
      METHODS: Qualitative evaluations in Malawi, Tanzania and South Africa (RSA) were
      conducted using key informant interviews (KIIs) and focus group discussions
      (FGDs) in each country to identify barriers and enablers of effective HIV/TB
      related CPD. Key stakeholders represented CPD implementers, regulators, and
      developers. HCWs were purposively sampled from high disease burden districts;
      each HCW completed brief, semi-structured questionnaires and participated in a
      FGD. KII and FGD results were combined into key themes spanning across countries
      using a grounded theory approach. RESULTS: Fifty-two KIIs were conducted: 17 in
      Malawi, 19 in Tanzania and 16 in RSA. Eighty-nine HCWs (24 from Malawi, 38 from
      Tanzania and 27 from RSA) completed questionnaires and participated in FGDs.
      Primarily, lack of sustainable financial resources and limitations in
      coordination of CPD result in poor accountability for CPD oversight and reduce
      CPD quality assurance. Healthcare worker shortages limit CPD opportunities,
      creating disparities in CPD access. CPD irrelevance and imbalance between HCW
      identified CPD needs and current programs reduce enthusiasm for CPD. Facility
      level constraints, including poor infrastructure and weak supply chains, restrict
      implementation of CPD skills and knowledge. Challenges are more severe in rural
      settings. CONCLUSION: To address identified gaps, sustainable funding, strong
      leadership and collaboration at every level are needed to strengthen CPD
      regulation and accreditation systems; increase CPD accessibility in the
      workplace; and create enabling environments for CPD implementation. Together,
      these improvements may improve TB/HIV CPD quality and patient outcomes.

PMID- 29040304
TI  - Characterization of the Zika virus induced small RNA response in Aedes aegypti
      cells.
AB  - RNA interference (RNAi) controls arbovirus infections in mosquitoes. Two
      different RNAi pathways are involved in antiviral responses: the PIWI-interacting
      RNA (piRNA) and exogenous short interfering RNA (exo-siRNA) pathways, which are
      characterized by the production of virus-derived small RNAs of 25-29 and 21
      nucleotides, respectively. The exo-siRNA pathway is considered to be the key
      mosquito antiviral response mechanism. In Aedes aegypti-derived cells, Zika virus
      (ZIKV)-specific siRNAs were produced and loaded into the exo-siRNA pathway
      effector protein Argonaute 2 (Ago2); although the knockdown of Ago2 did not
      enhance virus replication. Enhanced ZIKV replication was observed in a Dcr2
      knockout cell line suggesting that the exo-siRNA pathway is implicated in the
      antiviral response. Although ZIKV-specific piRNA-sized small RNAs were detected,
      these lacked the characteristic piRNA ping-pong signature motif and were bound to
      Ago3 but not Piwi5 or Piwi6. Silencing of PIWI proteins indicated that the
      knockdown of Ago3, Piwi5 or Piwi6 did not enhance ZIKV replication and only Piwi4
      displayed antiviral activity. We also report that the expression of ZIKV capsid
      (C) protein amplified the replication of a reporter alphavirus; although, unlike
      yellow fever virus C protein, it does not inhibit the exo-siRNA pathway. Our
      findings elucidate ZIKV-mosquito RNAi interactions that are important for
      understanding its spread.

PMID- 29040305
TI  - Switching and optimizing control for coal flotation process based on a hybrid
      model.
AB  - Flotation is an important part of coal preparation, and the flotation column is
      widely applied as efficient flotation equipment. This process is complex and
      affected by many factors, with the froth depth and reagent dosage being two of
      the most important and frequently manipulated variables. This paper proposes a
      new method of switching and optimizing control for the coal flotation process. A
      hybrid model is built and evaluated using industrial data. First, wavelet
      analysis and principal component analysis (PCA) are applied for signal pre
      processing. Second, a control model for optimizing the set point of the froth
      depth is constructed based on fuzzy control, and a control model is designed to
      optimize the reagent dosages based on expert system. Finally, the least squares
      support vector machine (LS-SVM) is used to identify the operating conditions of
      the flotation process and to select one of the two models (froth depth or reagent
      dosage) for subsequent operation according to the condition parameters. The
      hybrid model is developed and evaluated on an industrial coal flotation column
      and exhibits satisfactory performance.

PMID- 29040306
TI  - Micheliolide suppresses LPS-induced neuroinflammatory responses.
AB  - Microglia-involved neuroinflammation is thought to promote brain damage in
      various neurodegenerative disorders. Thus, inhibition of microglial over
      activation may have a therapeutic benefit for the treatment of neurodegenerative
      disorders. Micheliolide (MCL) is a sesquiterpene lactone which inhibits various
      inflammatory response. However, whether MCL can inhibit neuroinflammation caused
      by LPS-activated BV2 microglia has not yet been explored. In this study, we
      demonstrated that treatment of BV2 cells with MCL significantly repressed LPS
      stimulated nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression,
      as well as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and
      nitric oxide (NO) induction. MCL also attenuated mRNA levels of multiple pro
      inflammatory cytokines and mediators such as iNOS, COX-2, TNF-alpha, IL-6 and IL
      1beta. Mechanistic studies revealed that MCL suppressed LPS-stimulated the
      activation of IkappaBalpha/NF-kappaB pathway and Akt pathway. Moreover, MCL
      inhibited LPS-induced the activition of c-Jun N-terminal kinase (JNK), p38 MAPK
      kinase, and extracellular signal-regulated kinases 1/2 (ERK1/2). Meanwhile, MCL
      markedly promoted antioxidant protein heme oxygenase-1 (HO-1) expression by
      enhancing NF-E2-related factor 2 (Nrf2) activity. Together, our results imply
      that MCL may serve as a neuroprotective agent in neuroinflammation-related
      neurodegenerative disorders.

PMID- 29040307
TI  - Effects of biomass reducing agent on magnetic properties and phase transformation
      of Baotou low-grade limonite during magnetizing-roasting.
AB  - Biomass was used as reducing agent to roast the Baotou low-grade limonite in a
      high temperature vacuum atmosphere furnace. The effect of calcination
      temperature, time and ratio of reducing agent on the magnetic properties of
      calcined ore was studied by VSM. The phase and microstructure changes of limonite
      before and after calcination were analyzed by XRD and SEM. The results show that
      in the roasting process the phase transition process of the ferrous material in
      limonite is first dehydrated at high temperature to formalpha-Fe2O3, and then it
      is converted into Fe3O4 by the reduction of biomass. With the increase of
      calcination temperature, the magnetic properties of the calcined ore first
      increase and then decrease. When the temperature is higher than 650 degrees C,
      Fe3O4 will become Fe2SiO4, resulting in reduced the magnetic material in calcined
      ore and the magnetic weakened. The best magnetization effect was obtained when
      the roasting temperature is 550 degrees C, the percentage of biomass was 15% and
      the roasting time was 30min. The saturation magnetization can reach 60.13emu.g-1,
      the recovery of iron was 72% and the grade of iron was 58%.

PMID- 29040308
TI  - Thermostable proteins bioprocesses: The activity of restriction endonuclease
      methyltransferase from Thermus thermophilus (RM.TthHB27I) cloned in Escherichia
      coli is critically affected by the codon composition of the synthetic gene.
AB  - Obtaining thermostable enzymes (thermozymes) is an important aspect of
      biotechnology. As thermophiles have adapted their genomes to high temperatures,
      their cloned genes' expression in mesophiles is problematic. This is mainly due
      to their high GC content, which leads to the formation of unfavorable secondary
      mRNA structures and codon usage in Escherichia coli (E. coli). RM.TthHB27I is a
      member of a family of bifunctional thermozymes, containing a restriction
      endonuclease (REase) and a methyltransferase (MTase) in a single polypeptide.
      Thermus thermophilus HB27 (T. thermophilus) produces low amounts of RM.TthHB27I
      with a unique DNA cleavage specificity. We have previously cloned the wild type
      (wt) gene into E. coli, which increased the production of RM.TthHB27I over 100
      fold. However, its enzymatic activities were extremely low for an ORF expressed
      under a T7 promoter. We have designed and cloned a fully synthetic tthHB27IRM
      gene, using a modified 'codon randomization' strategy. Codons with a high GC
      content and of low occurrence in E. coli were eliminated. We incorporated a stem
      loop circuit, devised to negatively control the expression of this highly toxic
      gene by partially hiding the ribosome-binding site (RBS) and START codon in mRNA
      secondary structures. Despite having optimized 59% of codons, the amount of
      produced RM.TthHB27I protein was similar for both recombinant tthHB27IRM gene
      variants. Moreover, the recombinant wt RM.TthHB27I is very unstable, while the
      RM.TthHB27I resulting from the expression of the synthetic gene exhibited
      enzymatic activities and stability equal to the native thermozyme isolated from
      T. thermophilus. Thus, we have developed an efficient purification protocol using
      the synthetic tthHB27IRM gene variant only. This suggests the effect of co
      translational folding kinetics, possibly affected by the frequency of
      translational errors. The availability of active RM.TthHB27I is of practical
      importance in molecular biotechnology, extending the palette of available REase
      specificities.

PMID- 29040309
TI  - Targeted Pth4-expressing cell ablation impairs skeletal mineralization in
      zebrafish.
AB  - Skeletal development and mineralization are essential processes driven by the
      coordinated action of neural signals, circulating molecules and local factors.
      Our previous studies revealed that the novel neuropeptide Pth4, synthesized by
      hypothalamic cells, was involved in bone metabolism via phosphate regulation in
      adult zebrafish. Here, we investigate the role of pth4 during skeletal
      development using single-cell resolution, two-photon laser ablation of Pth4:eGFP
      expressing cells and confocal imaging in vivo. Using a stable transgenic
      Pth4:eGFP zebrafish line, we identify Pth4:eGFP-expressing cells as post-mitotic
      neurons. After targeted ablation of eGFP-expressing cells in the hypothalamus,
      the experimental larvae exhibited impaired mineralization of the craniofacial
      bones whereas cartilage development was normal. In addition to a decrease in pth4
      transcript levels, we noted altered expression of phex and entpd5, genes
      associated with phosphate homeostasis and mineralization, as well as a delay in
      the expression of osteoblast differentiation markers such as sp7 and sparc. Taken
      together, these results suggest that Pth4-expressing hypothalamic neurons
      participate in the regulation of bone metabolism, possibly through regulating
      phosphate balance during zebrafish development.

PMID- 29040310
TI  - Accumulation of advanced glycation end products evaluated by skin
      autofluorescence and incident frailty in older adults from the Bordeaux Three
      City cohort.
AB  - AIM: We analyzed the cross-sectional and prospective relationships between the
      accumulation of advanced glycation end products (AGE), assessed by skin
      autofluorescence (AF) and frailty and its components. METHODS: A total of 423
      participants of the Bordeaux sample of the Three-City study 75 years of age or
      older in 2009-2010 were included in the cross-sectional analysis. Among them, 255
      initially non-frail participants were re-examined 4 years later. Skin AF
      (arbitrary units (AU)) was measured using the AGE Reader. Frailty was defined
      using Fried's criteria. Associations were assessed with logistic regression
      models. RESULTS: Mean skin AF at baseline was 2.81 +/-0.68 AU and 16.8%
      participants were frail. Adjusted for sociodemographic and health
      characteristics, skin AF was associated neither with prevalent frailty as a whole
      (Odds Ratio (OR) = 1.2; 95% Confidence Interval: 0.8-1.9) nor with any of its
      components. Among 255 non-frail participants, 32 became frail over 4 years. In
      multivariate analyses, skin AF was not associated with incident frailty as a
      whole (OR = 1.0; 0.5-2.0) but with a doubled risk of incident exhaustion (OR =
      2.0; 1.2-3.6) and low energy expenditure (OR = 2.0; 1.1-3.7). No association was
      observed with other criteria. CONCLUSION: In French older community-dwellers aged
      75 years and over, the accumulation of AGEs evaluated by skin AF was not
      associated with prevalent or incident frailty but with the 4-year risk of
      exhaustion and low energy expenditure. Further studies with larger samples are
      needed to confirm our results.

PMID- 29040311
TI  - Putative endogenous filovirus VP35-like protein potentially functions as an IFN
      antagonist but not a polymerase cofactor.
AB  - It has been proposed that some non-retroviral RNA virus genes are integrated into
      vertebrate genomes. Endogenous filovirus-like elements (EFLs) have been
      discovered in some mammalian genomes. However, their potential roles in
      ebolavirus infection are unclear. A filovirus VP35-like element (mlEFL35) is
      found in the little brown bat (Myotis lucifugus) genome. Putative mlEFL35-derived
      protein (mlEFL35p) contains nearly full-length amino acid sequences corresponding
      to ebolavirus VP35. Ebola virus VP35 has been shown to bind double-stranded RNA,
      leading to inhibition of type I interferon (IFN) production, and is also known as
      a viral polymerase cofactor that is essential for viral RNA
      transcription/replication. In this study, we transiently expressed mlEFL35p in
      human kidney cells and investigated its biological functions. We first found that
      mlEFL35p was coimmunoprecipitated with itself and ebolavirus VP35s but not with
      the viral nucleoprotein. Then the biological functions of mlEFL35p were analyzed
      by comparing it to ebolavirus VP35s. We found that the expression of mlEFL35p
      significantly inhibited human IFN-beta promoter activity as well as VP35s. By
      contrast, expression of mlEFL35p did not support viral RNA
      transcription/replication and indeed slightly decrease the reporter gene
      expression in a minigenome assay. These results suggest that mlEFL35p potentially
      acts as an IFN antagonist but not a polymerase cofactor.

PMID- 29040312
TI  - End-tidal carbon dioxide measurement in preterm infants with low birth weight.
AB  - OBJECTIVE: There are conflicting data regarding the use of end-tidal carbon
      dioxide (PetCO2) measurement in preterm infants. The aim of this study was to
      evaluate the effects of different dead space to tidal volume ratios (VD/VT) on
      the correlation between PetCO2 and arterial carbon dioxide pressure (PaCO2) in
      ventilated preterm infants with respiratory distress syndrome (RDS). METHODS: We
      enrolled ventilated preterm infants (with assist control mode or synchronous
      intermittent mandatory mode) with RDS who were treated with surfactant in this
      prospective study. Simultaneous PetCO2 and PaCO2 data pairs were obtained from
      ventilated neonates monitored using mainstream capnography. Data obtained before
      and after surfactant treatment were also analyzed. RESULTS: One-hundred and one
      PetCO2 and PaCO2 pairs from 34 neonates were analyzed. There was a moderate
      correlation between PetCO2 and PaCO2 values (r = 0.603, P < 0.01). The
      correlation was higher in the post-surfactant treatment group (r = 0.786, P <
      0.01) than the pre-surfactant treatment group (r = 0.235). The values of PaCO2
      and PetCO2 obtained based on the treatment stage of surfactant therapy were 42.4
      +/- 8.6 mmHg and 32.6 +/- 7.2 mmHg, respectively, in pre-surfactant treatment
      group, and 37.8 +/- 10.3 mmHg and 33.7 +/- 9.3 mmHg, respectively, in the post
      surfactant treatment group. Furthermore, we found a significant decrease in VD/VT
      in the post-surfactant treatment group when compared to the pre-surfactant
      treatment group (P = 0.003). CONCLUSIONS: VD/VT decreased significantly after
      surfactant therapy and the correlation between PetCO2 and PaCO2 was higher after
      surfactant therapy in preterm infants with RDS.

PMID- 29040313
TI  - Premature aortic smooth muscle cell differentiation contributes to matrix
      dysregulation in Marfan Syndrome.
AB  - Thoracic aortic aneurysm and dissection are life-threatening complications of
      Marfan syndrome (MFS). Studies of human and mouse aortic samples from late stage
      MFS demonstrate increased TGF-beta activation/signaling and diffuse matrix
      changes. However, the role of the aortic smooth muscle cell (SMC) phenotype in
      early aneurysm formation in MFS has yet to be fully elucidated. As our objective,
      we investigated whether an altered aortic SMC phenotype plays a role in aneurysm
      formation in MFS. We describe previously unrecognized concordant findings in the
      aortas of a murine model of MFS, mgR, during a critical and dynamic phase of
      early development. Using Western blot, gelatin zymography, and histological
      analysis, we demonstrated that at postnatal day (PD) 7, before aortic TGF-beta
      levels are increased, there is elastic fiber fragmentation/disorganization and
      increased levels of MMP-2 and MMP-9. Compared to wild type (WT) littermates,
      aortic SMCs in mgR mice express higher levels of contractile proteins suggesting
      a switch to a more mature contractile phenotype. In addition, tropoelastin levels
      are decreased in mgR mice, a finding consistent with a premature switch to a
      contractile phenotype. Proliferation assays indicate a decrease in the
      proliferation rate of mgR cultured SMCs compared to WT SMCs. KLF4, a regulator of
      smooth muscle cell phenotype, was decreased in aortic tissue of mgR mice.
      Finally, overexpression of KLF4 partially reversed this phenotypic change in the
      Marfan SMCs. This study indicates that an early phenotypic switch appears to be
      associated with initiation of important metabolic changes in SMCs that contribute
      to subsequent pathology in MFS.

PMID- 29040314
TI  - Structure of 311 service requests as a signature of urban location.
AB  - While urban systems demonstrate high spatial heterogeneity, many urban planning,
      economic and political decisions heavily rely on a deep understanding of local
      neighborhood contexts. We show that the structure of 311 Service Requests enables
      one possible way of building a unique signature of the local urban context, thus
      being able to serve as a low-cost decision support tool for urban stakeholders.
      Considering examples of New York City, Boston and Chicago, we demonstrate how 311
      Service Requests recorded and categorized by type in each neighborhood can be
      utilized to generate a meaningful classification of locations across the city,
      based on distinctive socioeconomic profiles. Moreover, the 311-based
      classification of urban neighborhoods can present sufficient information to model
      various socioeconomic features. Finally, we show that these characteristics are
      capable of predicting future trends in comparative local real estate prices. We
      demonstrate 311 Service Requests data can be used to monitor and predict
      socioeconomic performance of urban neighborhoods, allowing urban stakeholders to
      quantify the impacts of their interventions.

PMID- 29040315
TI  - Individual and environmental correlates of objectively measured sedentary time in
      Dutch and Belgian adults.
AB  - As the detrimental health effects of sedentary behaviour are well established,
      insight into the individual and environmental factors that influence adults'
      sedentary behaviour is needed. Most studies to date rely on self-reported
      measures of sedentary time. Therefore, the aim of the current study was to
      examine individual and environmental correlates of objectively measured sedentary
      time in Dutch and Belgian adults. Between March and August 2014, Belgian (n =
      133) and Dutch (n = 223) adults, recruited as sub-sample of the SPOTLIGHT survey,
      wore an ActiGraph accelerometer to provide objectively measured sedentary and
      moderate to vigorous physical activity time. Participants completed a
      questionnaire assessing sociodemographic (country of residence, age, gender and
      educational level), lifestyle (sleep, smoking, sugar-containing beverage
      consumption, alcohol intake), health (body mass index, self-rated health), work
      (employment status and type of work), happiness, physical environmental (owning a
      car, number of screens, socioeconomic status and residential density) and social
      environmental factors (social network, social cohesion). Univariate and
      multivariable regression analyses showed that Belgian participants had a lower
      odds of being sedentary for at least 9 hours per day compared to Dutch
      participants. Women, older participants and those meeting the WHO recommendation
      for physical activity were also less likely to sit for 9 hours or more per day.
      Participants doing (heavy) manual work or being in education, homemaker,
      unemployed had lower odds of being sedentary for at least 9 hours per day
      compared to participants with a sitting job. Those with a higher self-reported
      social network also had lower odds for sedentary time. No associations between
      physical and other social environmental characteristics and sedentary time were
      found. Our findings add to the growing evidence of factors associated with
      prolonged sedentary time in adults. These findings may be used to inform the
      development of strategies and interventions aimed at reducing sedentary time, and
      to identify high risk groups.

PMID- 29040316
TI  - Rising trends and inequalities in cesarean section rates in Pakistan: Evidence
      from Pakistan Demographic and Health Surveys, 1990-2013.
AB  - Despite global efforts to improve maternal health, many developing countries
      including Pakistan have failed to achieve the target of a 75% reduction in
      maternal deaths by 2015. Addressing socioeconomic inequalities in access to
      emergency obstetric care is crucial for reducing the maternal mortality rate.
      This study was done to examine the time trends and socioeconomic inequalities in
      the utilization of cesarean section (C-section) in Pakistan during 1990-2013. We
      used data from the Pakistan Demographic and Health Surveys (PDHS) conducted
      during 1990 to 2013. All these surveys are nationally representative surveys of
      ever-married women aged 15-49 years with a sample size of 6611, 10,023, and
      13,558 women in 1990-1991, 2006-2007, and 2012-2013, respectively, with an
      overall response rate of over 90%. The unit of analysis for this study was women
      with their most recent live birth in the five years preceding the surveys.
      Bivariate analyses and multivariable logistic regression models were employed to
      investigate the prevalence of cesarean sections according to selected
      sociodemographic characteristics of women. C-section rates were found to have
      increased during this period, with an especially significant rise from 2.7% in
      1990-1991 to 15.8% in 2012-2013 with lower utilization among the non-educated
      women (7.5%), compared with the women with higher education (40.3%). C-section
      rates ranged from 5.5% in the poorest women to 35.3% in the richest women. Only
      11.5% of the rural women had a C-section compared to 25.6% of the urban women. A
      greater likelihood of having a cesarean section was observed in the richest,
      highly educated, and urban-living women while there was no significant difference
      observed in cesarean section rates between the private and public sectors in all
      three surveys. To improve maternal health, routine monitoring and evaluation of
      the provision of emergency obstetric services are needed to address the underuse
      of C-section in poor and rural areas and overuse in rich and urban areas.

PMID- 29040317
TI  - Economic benefits of sharing and redistributing influenza vaccines when shortages
      occurred.
AB  - BACKGROUND: Recurrent influenza outbreak has been a concern for government health
      institutions in Taiwan. Over 10% of the population is infected by influenza
      viruses every year, and the infection has caused losses to both health and the
      economy. Approximately three million free vaccine doses are ordered and
      administered to high-risk populations at the beginning of flu season to control
      the disease. The government recommends sharing and redistributing vaccine
      inventories when shortages occur. While this policy intends to increase inventory
      flexibility, and has been proven as widely valuable, its impact on vaccine
      availability has not been previously reported. MATERIAL AND METHODS: This study
      developed an inventory model adapted to vaccination protocols to evaluate
      government recommended polices under different levels of vaccine production.
      Demands were uncertain and stratified by ages and locations according to the
      demographic data in Taiwan. RESULTS: When vaccine supply is sufficient, sharing
      pediatric vaccine reduced vaccine unavailability by 43% and overstock by 54%, and
      sharing adult vaccine reduced vaccine unavailability by 9% and overstock by 15%.
      Redistributing vaccines obtained greater gains for both pediatrics and adults (by
      75%). When the vaccine supply is in short, only sharing pediatric vaccine yielded
      a 48% reduction of unused inventory, while other polices do not improve
      performances. CONCLUSIONS: When implementing vaccination activities for seasonal
      influenza intervention, it is important to consider mismatches of demand and
      vaccine inventory. Our model confirmed that sharing and redistributing vaccines
      can substantially increase availability and reduce unused vaccines.

PMID- 29040318
TI  - Rapid reversal of innate immune dysregulation in blood of patients and livers of
      humanized mice with HCV following DAA therapy.
AB  - RESULTS: First, in patients receiving two different combinations of DAAs, we
      found that DAAs induced not only rapid viral clearance, but also a re-setting of
      antiviral immune responses in the peripheral blood. Specifically, we see a rapid
      decline in the expression of genes associated with chronic IFN stimulation
      (IFIT3, USP18, IFIT1) as well as a rapid decline in genes associated with
      inflammation (IL1beta, CXCL10, CXCL11) in the peripheral blood that precedes the
      complete removal of virus from the blood. Interestingly, this rapid reversal of
      innate immune activation was not seen in patients who successfully clear chronic
      HCV infection using IFN-based therapy. Next, using a novel humanized mouse model
      (Fah-/-RAG2-/-IL2rgnull-FRG), we assessed the changes that occur in the hepatic
      tissue following DAA treatment. DAA-mediated rapid HCV clearance resulted in
      blunting of the expression of proinflammatory responses while functionally
      restoring the RIG-I/MAVS axis in the liver of humanized mice. CONCLUSIONS:
      Collectively, our data demonstrate that the rapid viral clearance following
      treatment with DAAs results in the rebalancing of innate antiviral response in
      both the peripheral blood and the liver as well as enhanced antiviral signaling
      within previously infected hepatocytes.

PMID- 29040319
TI  - Habitat selection and diurnal refugia of gray foxes in southwestern Georgia, USA.
AB  - Understanding habitat selection of gray foxes (Urocyon cinereoargenteus) is
      essential to evaluate their potential response to changes in land use and
      predator communities. Few studies have evaluated temporal habitat selection or
      explicitly identified habitats used by gray foxes for diurnal refugia. We used
      GPS collars to obtain location data for 34 gray foxes (20 males and 14 females)
      from February 2014 to December 2015 to evaluate temporal (seasonal and diel)
      habitat selection and selection of diurnal refugia in southwestern Georgia, USA.
      We analyzed habitat selection at 2 levels, selection of a core area within the
      home range and selection of locations within the home range. Habitat selection
      was non-random (P < 0.001) but consistent among seasons, between day and night,
      and between sexes (P > 0.05). Hardwoods, human use (i.e., areas associated with
      regular human activity such as buildings, lawns, parking areas, etc.), and roads
      were selected (P < 0.05), whereas pine dominated stands were used randomly (P >
      0.05). Selection of habitats for diurnal refugia did not vary seasonally or by
      sex (P > 0.05), with foxes selecting (P < 0.05) areas near hardwood forests,
      roads, agriculture, human use, pastures/food plots, and shrub scrub habitats.
      Gray foxes were observed on the ground while resting, and we found no evidence of
      gray foxes diurnally resting in trees. Our results suggest that on our study
      area, gray foxes are an edge species that prefer forests with a hardwood
      component in areas near human use and roads.

PMID- 29040320
TI  - Circulating microRNA-375 as biomarker of pancreatic beta cell death and
      protection of beta cell mass by cytoprotective compounds.
AB  - OBJECTIVE: Previous studies demonstrated that circulating microRNA-375 (miR-375)
      is a suitable plasma biomarker for real-time detection of beta cell death. The
      present study evaluated the use of this biomarker to assess the beta
      cytoprotective effect of phenylpropenoic acid glucoside (PPAG), which was
      previously demonstrated to protect beta cells against various types of injury,
      and of exendin-4, which is an established antidiabetic drug. METHODS: PPAG or
      exendin-4 were administered in mice treated with streptozotocin (STZ) to acutely
      induce beta cell death. Beta cell mass and apoptotic death were measured in
      pancreatic tissue sections. Circulating miR-375 was measured in blood plasma by
      RT-qPCR. The release of miR-375 was also measured in vitro by MIN-6 beta cells.
      RESULTS: Administration of STZ resulted in measurable circulating levels of miR
      375, a decrease in beta cell mass and increase in frequency of apoptotic beta
      cells. In vitro, there was a good correlation between miR-375 release and the
      extent of beta cell death. Treatment of mice with PPAG or exendin-4 significantly
      attenuated STZ-induced loss of beta cell mass and beta cell apoptosis, and
      normalized the blood level of miR-375. CONCLUSIONS: These findings show the
      potential use of serological miR-375 measurements to evaluate the beta
      cytoprotective effect of (potential) antidiabetic drugs in vivo.

PMID- 29040321
TI  - Co-delivery of micronized urinary bladder matrix damps regenerative capacity of
      minced muscle grafts in the treatment of volumetric muscle loss injuries.
AB  - Minced muscle grafts (MG) promote de novo muscle fiber regeneration and
      neuromuscular strength recovery in small and large animal models of volumetric
      muscle loss. The most noteworthy limitation of this approach is its reliance on a
      finite supply of donor tissue. To address this shortcoming, this study sought to
      evaluate micronized acellular urinary bladder matrix (UBM) as a scaffolding to
      promote in vivo expansion of this MG therapy in a rat model. Rats received
      volumetric muscle loss injuries to the tibialis anterior muscle of their left
      hind limb which were either left untreated or repaired with minced muscle graft
      at dosages of 50% and 100% of the defect mass, urinary bladder matrix in
      isolation, or a with an expansion product consisting of a combination of the two
      putative therapies in which the minced graft is delivered at a dosage of 50% of
      the defect mass. Rats survived to 2 and 8 weeks post injury before functional (in
      vivo neuromuscular strength), histological, morphological, and biochemical
      analyses were performed. Rats treated with the expansion product exhibited
      improved neuromuscular function relative to untreated VML after an 8 week time
      period following injury. This improvement in functional capacity, however, was
      accompanied with a concomitant reduction in graft mediated regeneration, as
      evidenced cell lineage tracing enable by a transgenic GFP expressing donor, and a
      mixed histological outcome indicating coincident fibrous matrix deposition with
      interspersed islands of nascent muscle fibers. Furthermore, quantitative
      immunofluorescence and transcriptional analysis following the 2 week time point
      suggests an exacerbated immune response to the UBM as a possible nidus for the
      observed suboptimal regenerative outcome. Moving forward, efforts related to the
      development of a MG expansion product should carefully consider the effects of
      the host immune response to candidate biomaterials in order to avoid undesirable
      dysregulation of pro-regenerative cross talk between the immune system and
      myogenic processes.

PMID- 29040323
TI  - The influence of alcohol consumption on sickness presenteeism and impaired daily
      activities. The WIRUS screening study.
AB  - BACKGROUND: Alcohol use is a global health issue and may influence activity
      performance in a variety of domains, including the occupational and domestic
      spheres. The aim of the study was to examine the influence of annual drinking
      frequency and binge drinking (>=6 units at one occasion) on activity impairments
      both at work (sickness presenteeism) and outside the workplace. METHODS:
      Employees (n = 3278), recruited from 14 Norwegian private and public companies,
      responded to a questionnaire containing questions from the Alcohol Use Disorders
      Identification Test (AUDIT) and the Workplace Productivity and Activity
      Impairment questionnaire (WPAI). RESULTS: Multiple hierarchical regression
      analyses revealed that binge drinking was associated with both sickness
      presenteeism and impaired daily activities, even after controlling for gender,
      age, educational level, living status and employment sector. Annual drinking
      frequency was associated with impaired daily activities, but not sickness
      presenteeism. CONCLUSIONS: Binge drinking seems to have a stronger influence on
      activity performance both at work and outside the workplace than drinking
      frequency. Interventions targeting alcohol consumption should benefit from
      focusing on binge drinking behavior.

PMID- 29040322
TI  - Dexamethasone-mediated inhibition of Glioblastoma neurosphere dispersal in an ex
      vivo organotypic neural assay.
AB  - Glioblastoma is highly aggressive. Early dispersal of the primary tumor renders
      localized therapy ineffective. Recurrence always occurs and leads to patient
      death. Prior studies have shown that dispersal of Glioblastoma can be
      significantly reduced by Dexamethasone (Dex), a drug currently used to control
      brain tumor related edema. However, due to high doses and significant side
      effects, treatment is tapered and discontinued as soon as edema has resolved.
      Prior analyses of the dispersal inhibitory effects of Dex were performed on
      tissue culture plastic, or polystyrene filters seeded with normal human
      astrocytes, conditions which inherently differ from the parenchymal architecture
      of neuronal tissue. The aim of this study was to utilize an ex-vivo model to
      examine Dex-mediated inhibition of tumor cell migration from low-passage, human
      Glioblastoma neurospheres on multiple substrates including mouse retina, and
      slices of mouse, pig, and human brain. We also determined the lowest possible Dex
      dose that can inhibit dispersal. Analysis by Two-Factor ANOVA shows that for GBM
      2 and GBM-3, Dex treatment significantly reduces dispersal on all tissue types.
      However, the magnitude of the effect appears to be tissue-type specific.
      Moreover, there does not appear to be a difference in Dex-mediated inhibition of
      dispersal between mouse retina, mouse brain and human brain. To estimate the
      lowest possible dose at which Dex can inhibit dispersal, LogEC50 values were
      compared by Extra Sum-of-Squares F-test. We show that it is possible to achieve
      50% reduction in dispersal with Dex doses ranging from 3.8 x10-8M to 8.0x10-9M
      for GBM-2, and 4.3x10-8M to 1.8x10-9M for GBM-3, on mouse retina and brain
      slices, respectively. These doses are 3-30-fold lower than those used to control
      edema. This study extends our previous in vitro data and identifies the mouse
      retina as a potential substrate for in vivo studies of GBM dispersal.

PMID- 29040324
TI  - The centrality of affective instability and identity in Borderline Personality
      Disorder: Evidence from network analysis.
AB  - We argue that the series of traits characterizing Borderline Personality Disorder
      samples do not weigh equally. In this regard, we believe that network approaches
      employed recently in Personality and Psychopathology research to provide
      information about the differential relationships among symptoms would be useful
      to test our claim. To our knowledge, this approach has never been applied to
      personality disorders. We applied network analysis to the nine Borderline
      Personality Disorder traits to explore their relationships in two samples drawn
      from university students and clinical populations (N = 1317 and N = 96,
      respectively). We used the Fused Graphical Lasso, a technique that allows
      estimating networks from different populations separately while considering their
      similarities and differences. Moreover, we examined centrality indices to
      determine the relative importance of each symptom in each network. The general
      structure of the two networks was very similar in the two samples, although some
      differences were detected. Results indicate the centrality of mainly affective
      instability, identity, and effort to avoid abandonment aspects in Borderline
      Personality Disorder. Results are consistent with the new DSM Alternative Model
      for Personality Disorders. We discuss them in terms of implications for therapy.

PMID- 29040325
TI  - TRIM5alpha SPRY/coiled-coil interactions optimize avid retroviral capsid
      recognition.
AB  - Restriction factors are important components of intrinsic cellular defense
      mechanisms against viral pathogens. TRIM5alpha is a restriction factor that
      intercepts the incoming capsid cores of retroviruses such as HIV and provides an
      effective species-specific barrier to retroviral infection. The TRIM5alpha SPRY
      domain directly binds the capsid with only very weak, millimolar-level affinity,
      and productive capsid recognition therefore requires both TRIM5alpha dimerization
      and assembly of the dimers into a multivalent hexagonal lattice to promote avid
      binding. Here, we explore the important unresolved question of whether the SPRY
      domains are flexibly linked to the TRIM lattice or more precisely positioned to
      maximize avidity. Biochemical and biophysical experiments indicate that the
      linker segment connecting the SPRY domain to the coiled-coil domain adopts an
      alpha-helical fold, and that this helical portion mediates interactions between
      the two domains. Targeted mutations were generated to disrupt the putative
      packing interface without affecting dimerization or higher-order assembly, and we
      identified mutant proteins that were nevertheless deficient in capsid binding in
      vitro and restriction activity in cells. Our studies therefore support a model
      wherein substantial avidity gains during assembly-mediated capsid recognition by
      TRIM5alpha come in part from tailored spacing of tethered recognition domains.

PMID- 29040326
TI  - Mycobacterium tuberculosis infection modulates adipose tissue biology.
AB  - Mycobacterium tuberculosis (Mtb) primarily resides in the lung but can also
      persist in extrapulmonary sites. Macrophages are considered the prime cellular
      habitat in all tissues. Here we demonstrate that Mtb resides inside adipocytes of
      fat tissue where it expresses stress-related genes. Moreover, perigonadal fat of
      Mtb-infected mice disseminated the infection when transferred to uninfected
      animals. Adipose tissue harbors leukocytes in addition to adipocytes and other
      cell types and we observed that Mtb infection induces changes in adipose tissue
      biology depending on stage of infection. Mice infected via aerosol showed
      infiltration of inducible nitric oxide synthase (iNOS) or arginase 1 (Arg1)
      negative F4/80+ cells, despite recruitment of CD3+, CD4+ and CD8+ T cells. Gene
      expression analysis of adipose tissue of aerosol Mtb-infected mice provided
      evidence for upregulated expression of genes associated with T cells and NK cells
      at 28 days post-infection. Strikingly, IFN-gamma-producing NK cells and Mtb
      specific CD8+ T cells were identified in perigonadal fat, specifically CD8+CD44
      CD69+ and CD8+CD44-CD103+ subpopulations. Gene expression analysis of these cells
      revealed that they expressed IFN-gamma and the lectin-like receptor Klrg1 and
      down-regulated CD27 and CD62L, consistent with an effector phenotype of Mtb
      specific CD8+ T cells. Sorted NK cells expressed higher abundance of Klrg1 upon
      infection, as well. Our results reveal the ability of Mtb to persist in adipose
      tissue in a stressed state, and that NK cells and Mtb-specific CD8+ T cells
      infiltrate infected adipose tissue where they produce IFN-gamma and assume an
      effector phenotype. We conclude that adipose tissue is a potential niche for Mtb
      and that due to infection CD8+ T cells and NK cells are attracted to this tissue.

PMID- 29040327
TI  - Epizootic to enzootic transition of a fungal disease in tropical Andean frogs:
      Are surviving species still susceptible?
AB  - The fungal pathogen Batrachochytrium dendrobatidis (Bd), which causes the disease
      chytridiomycosis, has been linked to catastrophic amphibian declines throughout
      the world. Amphibians differ in their vulnerability to chytridiomycosis; some
      species experience epizootics followed by collapse while others exhibit stable
      host/pathogen dynamics where most amphibian hosts survive in the presence of Bd
      (e.g., in the enzootic state). Little is known about the factors that drive the
      transition between the two disease states within a community, or whether
      populations of species that survived the initial epizootic are stable, yet this
      information is essential for conservation and theory. Our study focuses on a
      diverse Peruvian amphibian community that experienced a Bd-caused collapse. We
      explore host/Bd dynamics of eight surviving species a decade after the mass
      extinction by using population level disease metrics and Bd-susceptibility
      trials. We found that three of the eight species continue to be susceptible to
      Bd, and that their populations are declining. Only one species is growing in
      numbers and it was non-susceptible in our trials. Our study suggests that some
      species remain vulnerable to Bd and exhibit ongoing population declines in
      enzootic systems where Bd-host dynamics are assumed to be stable.

PMID- 29040328
TI  - Integrin beta 1 inhibition alleviates the chronic hyperproliferative dermatitis
      phenotype of SHARPIN-deficient mice.
AB  - SHARPIN (Shank-Associated RH Domain-Interacting Protein) is a component of the
      linear ubiquitin chain assembly complex (LUBAC), which enhances TNF-induced NF
      kappaB activity. SHARPIN-deficient (Sharpincpdm/cpdm) mice display multi-organ
      inflammation and chronic proliferative dermatitis (cpdm) due to TNF-induced
      keratinocyte apoptosis. In cells, SHARPIN also inhibits integrins independently
      of LUBAC, but it has remained enigmatic whether elevated integrin activity levels
      in the dermis of Sharpincpdm/cpdm mice is due to increased integrin activity or
      is secondary to inflammation. In addition, the functional contribution of
      increased integrin activation to the Sharpincpdm/cpdm phenotype has not been
      investigated. Here, we find increased integrin activity in keratinocytes from
      Tnfr1-/- Sharpincpdm/cpdm double knockout mice, which do not display chronic
      inflammation or proliferative dermatitis, thus suggesting that SHARPIN indeed
      acts as an integrin inhibitor in vivo. In addition, we present evidence for a
      functional contribution of integrin activity to the Sharpincpdm/cpdm skin
      phenotype. Treatment with an integrin beta 1 function blocking antibody reduced
      epidermal hyperproliferation and epidermal thickness in Sharpincpdm/cpdm mice.
      Our data indicate that, while TNF-induced cell death triggers the chronic
      inflammation and proliferative dermatitis, absence of SHARPIN-dependent integrin
      inhibition exacerbates the epidermal hyperproliferation in Sharpincpdm/cpdm mice.

PMID- 29040329
TI  - Sexual homicides in South Africa: A national cross-sectional epidemiological
      study of adult women and children.
AB  - METHODS: We conducted a retrospective national mortuary based study to identify
      all adult female homicides (18 years and older) and all child homicides (boys and
      girls < 18 years) in 2009 in a randomly selected, proportionate sample of
      mortuaries. Victim, perpetrator and crime data were collected in three processes:
      from the mortuary register, the autopsy report and from police with the
      identification of sexual homicides validated across the data collection
      processes. FINDINGS: Among the 2670 (95% CI: 2311-2979) adult women killed in
      2009, 494 (95% CI: 406-574) were identified as sexual homicides which was 19.8%
      (95% CI: 17.6-22.0) of all adult female homicides and among 1277 (95% CI: 1091
      1462) children killed in SA, sexual homicides were found in 104 (95% CI: 77-132)
      of the child homicides which was 8.7% (95% CI: 10.9-11.2%) of these murders.
      Strangulation was the most common cause of death for both children and adult
      females. A distinct age and sex pattern was found among children with only 1% boy
      child death identified as a sexual homicide and 92% of all the child sexual
      homicides were among girls. Strangulation was the most common manner of death
      among children (35.5%) and perpetrators were seldom strangers. However, no
      difference in the proportion of convictions between the sexual homicides and non
      sexual homicides were found for both adult females and children. CONCLUSION: Rape
      homicide is not a rare event in South Africa, with one in five female homicides
      and nearly one in ten child homicides identified with an associated sexual crime.
      These high prevalences are amongst the highest levels reported in the literature
      with our study among the few reporting on the epidemiology of child sexual
      homicide. Reducing mortality is an important policy goal for South Africa and for
      the rest of the world and the prevention of female and child homicide is an
      important part of attaining this goal.

PMID- 29040330
TI  - The association between toe grip strength and osteoarthritis of the knee in
      Japanese women: A multicenter cross-sectional study.
AB  - We evaluated the relationship between altered foot function and knee
      osteoarthritis through a specific comparison of toe grip strength in older women
      with and without knee osteoarthritis. Participants were 120 women with knee
      osteoarthritis (OA group) and 108 healthy community-dwelling women with no
      history of knee pain and lower limb surgery (control group). The following
      factors and outcome variables were included in our analysis: measured toe grip
      strength, isometric knee extension strength, the timed Up-and-Go, and the WOMAC
      scale. Between-group differences were compared using unpaired t-tests for
      descriptive characteristics and outcome measures. Pearson's correlation
      coefficients between toe grip strength and age, body mass index, and other
      outcome measures were calculated. Multiple logistic regression analysis was used
      to evaluate the independence of toe grip strength and knee osteoarthritis.
      Compared to the control group, participants in the OA group were older, heavier,
      and had a higher body mass index. Toe grip strength and isometric knee extension
      strength were lower and the timed Up-and-Go longer for the OA group than the
      control group. Toe grip strength was correlated with age negatively and isometric
      knee extension strength positively in the OA group and to age and the timed Up
      and-Go negatively, and isometric knee extension strength positively in the
      control group. Multiple logistic regression analysis revealed that body mass
      index, isometric knee extensor strength, and toe grip strength were independently
      associated with knee osteoarthritis. Our findings indicate a probable association
      between altered forefoot function and the incidence or progression of knee
      osteoarthritis. Increasing toe grip strength might provide a practical
      intervention for patients with knee osteoarthritis.

PMID- 29040332
TI  - The developmental programme for genesis of the entire kidney is recapitulated in
      Wilms tumour.
AB  - Wilms tumour (WT) is an embryonal tumour that recapitulates kidney development.
      The normal kidney is formed from two distinct embryological origins: the
      metanephric mesenchyme (MM) and the ureteric bud (UB). It is generally accepted
      that WT arises from precursor cells in the MM; however whether UB-equivalent
      structures participate in tumorigenesis is uncertain. To address the question of
      the involvement of UB, we assessed 55 Wilms tumours for the molecular features of
      MM and UB using gene expression profiling, immunohistochemsitry and
      immunofluorescence. Expression profiling primarily based on the Genitourinary
      Molecular Anatomy Project data identified molecular signatures of the UB and
      collecting duct as well as those of the proximal and distal tubules in the
      triphasic histology group. We performed immunolabeling for fetal kidneys and WTs.
      We focused on a central epithelial blastema pattern which is the characteristic
      of triphasic histology characterized by UB-like epithelial structures surrounded
      by MM and MM-derived epithelial structures, evoking the induction/aggregation
      phase of the developing kidney. The UB-like epithelial structures and surrounding
      MM and epithelial structures resembling early glomerular epithelium, proximal and
      distal tubules showed similar expression patterns to those of the developing
      kidney. These observations indicate WTs can arise from a precursor cell capable
      of generating the entire kidney, such as the cells of the intermediate mesoderm
      from which both the MM and UB are derived. Moreover, this provides an explanation
      for the variable histological features of mesenchymal to epithelial
      differentiation seen in WT.

PMID- 29040331
TI  - Primary care models for treating opioid use disorders: What actually works? A
      systematic review.
AB  - BACKGROUND: Primary care-based models for Medication-Assisted Treatment (MAT)
      have been shown to reduce mortality for Opioid Use Disorder (OUD) and have
      equivalent efficacy to MAT in specialty substance treatment facilities.
      OBJECTIVE: The objective of this study is to systematically analyze current
      evidence-based, primary care OUD MAT interventions and identify program
      structures and processes associated with improved patient outcomes in order to
      guide future policy and implementation in primary care settings. DATA SOURCES:
      PubMed, EMBASE, CINAHL, and PsychInfo. METHODS: We included randomized controlled
      or quasi experimental trials and observational studies evaluating OUD treatment
      in primary care settings treating adult patient populations and assessed
      structural domains using an established systems engineering framework. RESULTS:
      We included 35 interventions (10 RCTs and 25 quasi-experimental interventions)
      that all tested MAT, buprenorphine or methadone, in primary care settings across
      8 countries. Most included interventions used joint multi-disciplinary (specialty
      addiction services combined with primary care) and coordinated care by physician
      and non-physician provider delivery models to provide MAT. Despite large
      variability in reported patient outcomes, processes, and tasks/tools used,
      similar key design factors arose among successful programs including integrated
      clinical teams with support staff who were often advanced practice clinicians
      (nurses and pharmacists) as clinical care managers, incorporating patient
      "agreements," and using home inductions to make treatment more convenient for
      patients and providers. CONCLUSIONS: The findings suggest that multidisciplinary
      and coordinated care delivery models are an effective strategy to implement OUD
      treatment and increase MAT access in primary care, but research directly
      comparing specific structures and processes of care models is still needed.

PMID- 29040333
TI  - The role of parental education in child disability in China from 1987 to 2006.
AB  - This paper aimed to investigate the role of parental education in child
      disability in China. We used nationally representative data from China's National
      Sample Survey on Disability, iterated twice, in 1987 and 2006, with data of
      764,718 children aged 0-14 years. Logit models were used for statistical
      analysis. Results showed that the prevalence of child disability was
      significantly associated with each parent's education. Maternal education was
      more important than paternal education in child disability in both surveys. The
      analysis of marginal effect indicated a one-year increase in maternal and
      paternal schooling led to an average decrease of 0.121% and 0.091% in the
      probability of child disability in 1987, and 19 years later, these figures had
      dwindled to 0.091% and 0.072%, respectively.

PMID- 29040334
TI  - Advanced maternal age and adverse pregnancy outcomes: A systematic review and
      meta-analysis.
AB  - BACKGROUND: Advanced maternal age (AMA; >=35 years) is an increasing trend and is
      reported to be associated with various pregnancy complications. OBJECTIVE: To
      determine the risk of stillbirth and other adverse pregnancy outcomes in women of
      AMA. SEARCH STRATEGY: Embase, Medline (Ovid), Cochrane Database of Systematic
      Reviews, ClinicalTrials.gov, LILACS and conference proceedings were searched from
      >=2000. SELECTION CRITERIA: Cohort and case-control studies reporting data on one
      or more co-primary outcomes (stillbirth or fetal growth restriction (FGR)) and/or
      secondary outcomes in mothers >=35 years and <35 years. DATA COLLECTION AND
      ANALYSIS: The effect of age on pregnancy outcome was investigated by random
      effects meta-analysis and meta-regression. Stillbirth rates were correlated to
      rates of maternal diabetes, obesity, hypertension and use of assisted
      reproductive therapies (ART). MAIN RESULTS: Out of 1940 identified titles; 63
      cohort studies and 12 case-control studies were included in the meta-analysis.
      AMA increased the risk of stillbirth (OR 1.75, 95%CI 1.62 to 1.89) with a
      population attributable risk of 4.7%. Similar trends were seen for risks of FGR,
      neonatal death, NICU unit admission restriction and GDM. The relationship between
      AMA and stillbirth was not related to maternal morbidity or ART. CONCLUSIONS:
      Stillbirth risk increases with increasing maternal age. This is not wholly
      explained by maternal co-morbidities and use of ART. We propose that placental
      dysfunction may mediate adverse pregnancy outcome in AMA. Further prospective
      studies are needed to directly test this hypothesis.

PMID- 29040336
TI  - Characteristics of private partners in Chiranjeevi Yojana, a public-private
      partnership to promote institutional births in Gujarat, India - Lessons for
      universal health coverage.
AB  - BACKGROUND: The Chiranjeevi Yojana (CY) is a Public-Private-Partnership between
      the state and private obstetricians in Gujarat, India, since 2007. The state pays
      for institutional births of the most vulnerable households (below-poverty-line
      and tribal) in private hospitals. An innovative remuneration package has been
      designed to disincentivise unnecessary cesareans. This study examines
      characteristics of private facilities which participated in the program. METHODS:
      We conducted a cross-sectional survey of all facilities which had conducted any
      births between June 2012 and April 2013 in three districts. We identified 111
      private and 47 public facilities. Ninety of the 111 private facilities did
      caesarean sections in the last three months and were eligible to participate in
      the CY program. Of these, 40 (44%) participated in the CY program. We conducted
      descriptive and bivariate analyses followed by a Poisson regression model to
      estimate prevalence ratios of facility characteristics that predicted
      participation. RESULTS: We found that facilities participating in the CY program
      had a significantly higher likelihood of being general facilities (PR 1.9, 95% CI
      1.3-2.9), or conducting lower proportion of cesarean births (PR 2.1, 95% CI 1.2
      3.5) or having obstetricians new in private practice (PR 1.9, 95% CI 1.2-3.1) or
      being less expensive (PR 1.8, 95% CI 1.1-3.0). But none of these factors retained
      significance in a multi variable model. CONCLUSION: Private obstetricians who
      participate in the CY program tend to be new to private practice, provide general
      services, conduct fewer caesareans and are also less expensive. This is
      advantageous to the PPP and widens the target beneficiary groups that can be
      serviced by the PPP. The state should design remuneration packages with the aim
      of attracting relatively new obstetricians to set up practices in more remote
      areas. It is possible that the CY remuneration package design is effective in
      keeping caesarean rates in check, and needs to be studied further.

PMID- 29040335
TI  - Is patient empowerment the key to promote adherence? A systematic review of the
      relationship between self-efficacy, health locus of control and medication
      adherence.
AB  - BACKGROUND: Current health policies emphasize the need for an equitable doctor
      patient relationship, and this requires a certain level of patient empowerment.
      However, a systematic review of the empirical evidence on how empowerment affects
      medication adherence-the extent to which patients follow the physician's
      prescription of medication intake-is still missing. The goal of this systematic
      review is to sum up current state-of-the-art knowledge concerning the
      relationship between patient empowerment and medication adherence across medical
      conditions. As our conceptualization defines health locus of control and self
      efficacy as being crucial components of empowerment, we explored the relationship
      between these two constructs and medication adherence. METHODS: Relevant studies
      were retrieved through a comprehensive search of Medline and PsychINFO databases
      (1967 to 2017). In total, 4903 publications were identified. After applying
      inclusion and exclusion criteria and quality assessment, 154 articles were deemed
      relevant. Peer-reviewed articles, written in English, addressing the relationship
      between empowerment (predictor) and medication adherence (outcome) were included.
      FINDINGS: High levels of self-efficacy and Internal Health Locus of Control are
      consistently found to promote medication adherence. External control dimensions
      were found to have mainly negative (Chance and God attributed control beliefs) or
      ambiguous (Powerful others attributed control beliefs) links to adherence, except
      for Doctor Health Locus of Control which had a positive association with
      medication adherence. To fully capture how health locus of control dimensions
      influence medication adherence, the interaction between the sub-dimensions and
      the attitudinal symmetry between the doctor and patient, regarding the patient's
      control over the disease management, can provide promising new alternatives.
      DISCUSSION: The beneficial effect of patients' high internal and concurrent
      physician-attributed control beliefs suggests that a so-called "joint
      empowerment" approach can be suitable in order to foster medication adherence,
      enabling us to address the question of control as a versatile component in the
      doctor-patient relationship.

PMID- 29040338
TI  - Classifying dermoscopic patterns of naevi in a case-control study of melanoma.
AB  - Changes in dermoscopic patterns of naevi may be associated with melanoma;
      however, there is no consensus on which dermoscopic classification system is
      optimal. To determine whether different classification systems give comparable
      results and can be combined for analysis, we applied two systems to a case
      control study of melanoma with 1037 participants: 573 classified using a "1/3
      major feature" system, 464 classified based on rules of appearance, and 263
      classified with both criteria. There was strong correlation for non-specific
      (Spearman R = 0.96) and reticular (Spearman R = 0.82) naevi, with a slight bias
      for globular naevi with the rules of appearance system. Inter-observer
      reliability was high for the rules of appearance system, particularly for
      reticular naevi (Pearson >0.97). We show that different classification systems
      for naevi can be combined for data analysis, and describe a method for
      determining what adjustments may need to be applied to combine data sets.

PMID- 29040337
TI  - A comparison of extended spectrum beta-lactamase producing Escherichia coli from
      clinical, recreational water and wastewater samples associated in time and
      location.
AB  - Extended spectrum beta-lactamase producing Escherichia coli (ESBL-EC) are
      excreted via effluents and sewage into the environment where they can re
      contaminate humans and animals. The aim of this observational study was to detect
      and quantify ESBL-EC in recreational water and wastewater, and perform a genetic
      and phenotypic comparative analysis of the environmental strains with
      geographically associated human urinary ESBL-EC. Recreational fresh- and
      saltwater samples from four different beaches and wastewater samples from a
      nearby sewage plant were filtered and cultured on differential and ESBL-selective
      media. After antimicrobial susceptibility testing and multi-locus variable number
      of tandem repeats assay (MLVA), selected ESBL-EC strains from recreational water
      were characterized by whole genome sequencing (WGS) and compared to wastewater
      and human urine isolates from people living in the same area. We detected ESBL-EC
      in recreational water samples on 8/20 occasions (40%), representing all sites.
      The ratio of ESBL-EC to total number of E. coli colony forming units varied from
      0 to 3.8%. ESBL-EC were present in all wastewater samples in ratios of 0.56
      0.75%. ST131 was most prevalent in urine and wastewater samples, while ST10
      dominated in water samples. Eight STs and identical ESBL-EC MLVA-types were
      detected in all compartments. Clinical ESBL-EC isolates were more likely to be
      multidrug-resistant (p<0.001). This study confirms that ESBL-EC, including those
      that are capable of causing human infection, are present in recreational waters
      where there is a potential for human exposure and subsequent gut colonisation and
      infection in bathers. Multidrug-resistant E. coli strains are present in urban
      aquatic environments even in countries where antibiotic consumption in both
      humans and animals is highly restricted.

PMID- 29040340
TI  - Measuring local depletion of terrestrial game vertebrates by central-place
      hunters in rural Amazonia.
AB  - The degree to which terrestrial vertebrate populations are depleted in tropical
      forests occupied by human communities has been the subject of an intense
      polarising debate that has important conservation implications. Conservation
      ecologists and practitioners are divided over the extent to which community-based
      subsistence offtake is compatible with ecologically functional populations of
      tropical forest game species. To quantify depletion envelopes of forest
      vertebrates around human communities, we deployed a total of 383 camera trap
      stations and 78 quantitative interviews to survey the peri-community areas
      controlled by 60 semi-subsistence communities over a combined area of over 3.2
      million hectares in the Medio Jurua and Uatuma regions of Central-Western
      Brazilian Amazonia. Our results largely conform with prior evidence that hunting
      large-bodied vertebrates reduces wildlife populations near settlements, such that
      they are only found at a distance to settlements where they are hunted less
      frequently. Camera trap data suggest that a select few harvest-sensitive species,
      including lowland tapir, are either repelled or depleted by human communities.
      Nocturnal and cathemeral species were detected relatively more frequently in
      disturbed areas close to communities, but individual species did not necessarily
      shift their activity patterns. Group biomass of all species was depressed in the
      wider neighbourhood of urban areas rather than communities. Interview data
      suggest that species traits, especially group size and body mass, mediate these
      relationships. Large-bodied, large-group-living species are detected farther from
      communities as reported by experienced informants. Long-established communities
      in our study regions have not "emptied" the surrounding forest. Low human
      population density and low hunting offtake due to abundant sources of alternative
      aquatic protein, suggest that these communities represent a best-case scenario
      for sustainable hunting of wildlife for food, thereby providing a conservative
      assessment of game depletion. Given this 'best-case' camera trap and interview
      based evidence for hunting depletion, regions with higher human population
      densities, external trade in wildlife and limited access to alternative protein
      will likely exhibit more severe depletion.

PMID- 29040339
TI  - Protein tyrosine phosphatase PTPN22 is dispensable for dendritic cell antigen
      processing and promotion of T-cell activation by dendritic cells.
AB  - The PTPN22R620W single nucleotide polymorphism increases the risk of developing
      multiple autoimmune diseases including type 1 diabetes, rheumatoid arthritis and
      lupus. PTPN22 is highly expressed in antigen presenting cells (APCs) where the
      expression of the murine disease associated variant orthologue (Ptpn22R619W) is
      reported to dysregulate pattern recognition receptor signalling in dendritic
      cells (DCs) and promote T-cell proliferation. Because T-cell activation is
      dependent on DC antigen uptake, degradation and presentation, we analysed the
      efficiency of these functions in splenic and GM-CSF bone marrow derived DC from
      wild type (WT), Ptpn22-/- or Ptpn22R619W mutant mice. Results indicated no
      differential ability of DCs to uptake antigen via macropinocytosis or receptor
      mediated endocytosis. Antigen degradation and presentation was also equal as was
      WT T-cell conjugate formation and subsequent T-cell proliferation. Despite the
      likely presence of multiple phosphatase-regulated pathways in the antigen uptake,
      processing and presentation pathways that we investigated, we observed that
      Ptpn22 and the R619W autoimmune associated variant were dispensable. These
      important findings indicate that under non-inflammatory conditions there is no
      requirement for Ptpn22 in DC dependent antigen uptake and T-cell activation. Our
      findings reveal that perturbations in antigen uptake and processing, a
      fundamental pathway determining adaptive immune responses, are unlikely to
      provide a mechanism for the risk associated with the Ptpn22 autoimmune associated
      polymorphism.

PMID- 29040343
TI  - Spherical nematic shells with a prolate ellipsoidal core.
AB  - Liquid crystal shells have attracted considerable attention in recent years. In
      such systems, a combination of confinement and curvature generates topological
      defect structures that do not exist in the bulk. Past studies, however, have
      largely focused on perfectly spherical shells, and little attention has been
      devoted to the impact of core geometry on the configuration and arrangement of
      topological defects. In this work, a microfluidic glass capillary device is used
      to encapsulate spherical and prolate ellipsoidal particles in nematic liquid
      crystal (LC) droplets dispersed in aqueous media. Our experimental studies show
      that, when trapped inside a radial LC droplet, spherical particles with both
      homeotropic and planar anchoring are highly localized at the droplet's center.
      While the radial configuration of the LC droplets is not altered by a homeotropic
      particle, polystyrene particles with strong planar anchoring disturb the radial
      ordering, leading to a twisted structure. Experiments indicate that off-center
      particle positions can also arise, in which defects are displaced towards the
      vicinity of the droplet's surface. In contrast, when prolate ellipsoidal
      particles are encapsulated in a thick radial LC shell, the minimum free energy
      corresponds to configurations where the particle is positioned at the droplet
      center. In this case, defects arise at the two ends of the prolate ellipsoid,
      where the curvature of the particle is maximal, leading to the formation of
      peculiar hybrid and twisted structures.

PMID- 29040342
TI  - Area-level poverty, race/ethnicity & dialysis star ratings.
AB  - The Centers for Medicare and Medicaid Services recently released a five star
      rating system as part of 'Dialysis Facility Compare' to help patients identify
      and choose high performing clinics in the US. Eight dialysis-related measures
      determine ratings. Little is known about the association between surrounding
      community sociodemographic characteristics and star ratings. Using data from the
      U.S. Census and over 6000 dialysis clinics across the country, we examined the
      association between dialysis clinic star ratings and characteristics of the local
      population: 1) proportion of population below the federal poverty level (FPL); 2)
      proportion of black individuals; and 3) proportion of Hispanic individuals, by
      correlation and regression analyses. Secondary analyses with Quality Incentive
      Program (QIP) scores and population characteristics were also performed. We
      observed a negligible correlation between star ratings and the proportion of
      local individuals below FPL; Spearman coefficient, R = -0.09 (p<0.0001), and a
      stronger correlation between star ratings and the proportion of black
      individuals; R = -0.21 (p<0.0001). Ordered logistic regression analyses yielded
      adjusted odds ratio of 0.91 (95% confidence interval [0.80-1.30], p = 0.12) and
      0.55 ([0.48-0.63], p<0.0001) for high vs. low level of proportion below FPL and
      proportion of black individuals, respectively. In contrast, a near-zero
      correlation was observed between star ratings and the proportion of Hispanic
      individuals. Correlations varied substantially by country region, clinic profit
      status and clinic size. Analyses using clinic QIP scores provided similar
      results. Sociodemographic characteristics of the surrounding community, factors
      typically outside of providers' direct control, have varying levels of
      association with clinic dialysis star ratings.

PMID- 29040341
TI  - Predictors of mortality and ICD shock therapy in primary prophylactic ICD
      patients-A systematic review and meta-analysis.
AB  - BACKGROUND: There is evidence that the benefit of a primary prophylactic ICD
      therapy is not equal in all patients. PURPOSE: To evaluate risk factors of
      appropriate shocks and all- cause mortality in patients with a primary
      prophylactic ICD regarding contemporary studies. DATA SOURCE: PubMed, LIVIVO,
      Cochrane CENTRAL between 2010 and 2016. STUDY SELECTION: Studies were eligible if
      at least one of the endpoints of interest were reported. DATA EXTRACTION: All
      abstracts were independently reviewed by at least two authors. The full text of
      all selected studies was then analysed in detail. DATA SYNTHESIS: Our search
      strategy retrieved 608 abstracts. After exclusion of unsuitable studies, 36
      papers with a total patient number of 47282 were included in our analysis. All
      cause mortality was significantly associated with increasing age (HR 1.41, CI
      1.29-1.53), left ventricular function (LVEF; HR 1.21, CI 1.14-1.29), ischemic
      cardiomyopathy (ICM; HR 1.37, CI 1.14-1.66) and co-morbidities such as impaired
      renal function (HR 2.30, CI 1.97-2.69). Although, younger age (HR 0.96, CI 0.85
      1.09), impaired LVEF (HR 1.26, CI 0.89-1.78) and ischemic cardiomyopathy (HR
      2.22, CI 0.83-5.93) were associated with a higher risk of appropriate shocks,
      none of these factors reached statistical significance. LIMITATIONS: Individual
      patient data were not available for most studies. CONCLUSION: In this meta
      analysis of contemporary clinical studies, all-cause mortality is predicted by a
      variety of clinical characteristics including LVEF. On the other hand, the risk
      of appropriate shocks might be associated with impaired LVEF and ischemic
      cardiomyopathy. Further prospective studies are required to verify risk factors
      for appropriate shocks other than LVEF to help select appropriate patients for
      primary prophylactic ICD-therapy.

PMID- 29040344
TI  - Dilemmas for guardians of advanced dementia patients regarding tube feeding.
AB  - Background: advanced dementia is an incurable illness, its last stage marked by
      inability to eat. Tube feeding was deemed a helpful solution at this stage, but
      in recent years its inefficiency has been proved, and it is no longer practiced
      in many countries around the world. In Israel, however, the procedure is still
      accepted. In the gastroenterology department at the Bnai Zion Medical Center, a
      serious interaction is ongoing with patients' legal guardians, where detailed
      information is given about the inefficiency of the tube procedure. Nevertheless,
      the great majority of guardians choose to have it performed. Purpose: to probe
      the considerations underlying the decision for gastrostomy, despite the data and
      the recommendations. Method: qualitative research, including participant
      observation at the clinic and in-depth interviews with guardians. Findings: the
      families of most patients did not discuss end-of-life issues with them. The
      overwhelming preference for using the technology was interpreted as life-saving,
      in contrast to comfort feeding, which was deemed euthanasia. The reasons given
      for the decision to tube feed were drawn from a range of outlooks: religion, the
      patient's earlier survival capacity, and pragmatic considerations involving
      relations with nursing home staff. Conclusion: study of the decision-making
      process of advanced dementia patients' guardians sheds light on the layers of
      meaning of the Israeli discourse regarding end-of-life issues.

PMID- 29040345
TI  - Eight-Year Safety Data for Round and Anatomical Silicone Gel Breast Implants.
AB  - Background: The safety and efficacy of all medical devices, including breast
      implants, is important and consistent performance is best shown by undertaking
      long-term clinical and vigilance studies. Local complications such as capsular
      contracture and rupture are risks often associated with breast implant surgery.
      Objectives: The authors investigate and evaluate the safety and performance of
      Eurosilicone's (Eurosilicone S.A.S, Apt Cedex, France) Cristalline Paragel breast
      implants at 8 years postimplantation. Methods: In this prospective clinical
      study, 995 Eurosilicone textured cohesive Cristalline Paragel mammary implants
      were implanted in 526 women undergoing augmentation and reconstructive surgery at
      17 centers across France. Complications were recorded at 3 months and annually
      thereafter for 8 years. Descriptive statistics were used and key complications
      were analysed using the Kaplan-Meier method. Results: Capsular contracture was
      reported in 8.5% of implants across all cohorts through 8 years. The Kaplan-Meier
      risk of capsular contracture (Baker Grade III/IV) per implant was 8.4% in the
      primary augmentation cohort and 18.0% in the primary reconstruction cohort. Eight
      implant ruptures were identified by surgeon examination during this follow-up
      period. The Kaplan-Meier risk of rupture occurring within 8 years
      postimplantation, across all cohorts, was 1.4% per patient and 0.9% per implant.
      Actual implant removal rate (explantation/exchange) was 6.0% and 13.8% for
      primary augmentation and primary reconstruction, respectively. Actual rates of
      local complications including infection and seroma were low with risk rates of
      0.6% and 0.2% by subject. Conclusions: This multicenter clinical study involving
      Eurosilicone's silicone gel breast implants in both round and shaped profiles
      demonstrates an excellent safety and efficacy profile through 8 years.

PMID- 29040346
TI  - Heterogeneity in Body Contouring Outcomes Based Research: The Pittsburgh Body
      Contouring Complication Reporting System.
AB  - Background: Body contouring complications after massive weight loss (MWL) vary
      significantly in frequency and type. Currently, no standardized recommendations
      exist regarding which complications are most important to report. Objectives: We
      aim to provide a guideline for complication reporting in the body contouring
      literature. The Pittsburgh Body Contouring Complication Reporting System (PBCCRS)
      will aid in risk stratification of body contouring procedures and will decrease
      under-, over-, and nonreporting of complications. Methods: The authors reviewed
      the literature for the terms "body contouring," "MWL," and "complications."
      Elimination criteria included: non-English language, case report, meta-analysis,
      outpatient, non-MWL, unclear demographics, N <30 and lack of numeric results.
      Data were analyzed in 2 groups: truncal contouring and extremity contouring.
      Results: Eighty-nine papers were reviewed and 21 met inclusion criteria. The
      weighted mean rates as percentages for complications in the extremity group were:
      dehiscence (29.0), seroma (18.6), scarring (14.9), infection (8.8), lymphedema
      (7.8), hematoma (3.5), necrosis (1.9), deep venous thrombosis (DVT) or pulmonary
      embolism (PE) (0), and death (0). In the truncal group, weighted mean
      complication rates as percentages were: dehiscence (15.4), seroma (13.1),
      scarring (2.9), infection (9.4), lymphedema (1.3), hematoma (6.4), necrosis
      (7.2), DVT/PE (1.5), and death (0.6). Lymphedema was seldom reported, and suture
      extrusion was not reported in any selected papers. Weighted mean rates of DVT/PE
      in the extremity vs truncal contouring groups were significantly different.
      Differences in rates of scarring, lymphedema, and hematoma rates neared
      significance. Conclusions: Heterogeneity amongst selected studies is explained by
      variability in how complications are defined. The Pittsburgh Body Contouring
      Complication Reporting System provides suggested recommendations on complication
      reporting in massive weight loss body contouring surgery.

PMID- 29040347
TI  - Frailty index as a predictor of mortality: a systematic review and meta-analysis.
AB  - Background: two popular operational definitions of frailty, the frailty phenotype
      and Frailty index (FI), are based on different theories. Although FI was shown to
      be superior in predicting mortality to the frailty phenotype, no meta-analysis on
      mortality risk according to FI has been found in the literature. Methods: an
      electronic systematic literature search was conducted in August 2016 using four
      databases (Embase, Medline, CINAHL and PsycINFO) for prospective cohort studies
      published in 2000 or later, examining the mortality risk according to frailty
      measured by FI. A meta-analysis was performed to synthesise pooled mortality risk
      estimates. Results: of 2,617 studies identified by the systematic review, 18
      cohorts from 19 studies were included. Thirteen cohorts showed hazard ratios
      (HRs) per 0.01 increase in FI, six cohorts showed HRs per 0.1 increase in FI and
      two cohorts each showed odds ratios (ORs) per 0.01 and 0.1 increase in FI,
      respectively. All meta-analyses suggested that higher FI was significantly
      associated with higher mortality risk (pooled HR per 0.01 FI increase = 1.039,
      95% CI = 1.033-1.044, P < 0.001; pooled HR per 0.1 FI increase = 1.282, 95% CI =
      1.258-1.307, P < 0.001; pooled OR per 0.01 FI increase = 1.054, 95% CI = 1.040
      1.068, P < 0.001; pooled OR per 0.1 FI increase = 1.706, 95% CI = 1.547-1.881, P
      < 0.001). Meta-regression analysis among 13 cohorts with HR per 0.01 increase in
      FI showed that the studies with shorter follow-up periods and with lower female
      proportion were associated with higher mortality risks by FI. Conclusions: this
      systematic review and meta-analysis was the first to quantitatively demonstrate
      that frailty measured by the FI is a significant predictor of mortality.

PMID- 29040348
TI  - deSUMOylation signaling: a novel mechanism of liver CSC properties and
      hepatocarcinogenesis in hypoxia.

PMID- 29040349
TI  - Female-to-Male Gender Affirming Top Surgery: A Single Surgeon's 15-Year
      Retrospective Review and Treatment Algorithm.
AB  - Background: Mastectomy, referred to here as "Top Surgery," is an important
      surgical step for female-to-male (FTM) transgender patients. The goal is to
      excise breast tissue and create a masculine chest contour. Despite the rising
      demand for Top Surgery, debate still exists regarding how to select the most
      appropriate surgical technique to optimize aesthetic outcomes safely. Objectives:
      To determine the safety profile and aesthetic outcome of one surgeon's 15-year
      FTM Top Surgery experience. To provide an algorithm for FTM surgery technique
      selection based on this experience. Methods: A retrospective chart review was
      performed on 679 FTM patients (1358 mastectomies) undergoing Top Surgery from
      October 2001 to July 2016. The author's Top Surgery algorithm utilizes two
      techniques, "Keyhole" and "Double Incision Free Nipple Graft (DIFNG)," based on
      breast ptosis, inferior vertical skin pinch, and skin elasticity. Demographic
      data, operative details, complications, and reoperations along with their reasons
      were collected and analyzed. Results: Of the 679 patients, 15.3% underwent
      Keyhole and the remaining 84.7% underwent DIFNG procedure. The total complication
      rate was 18.1% and the total reoperation rate was 11.2% and these rates were
      shown to decrease over time. The two techniques differed significantly (P <
      0.001) in operating time (136 vs 102 min), breast weight excised (215 vs 638 g),
      and complication rate (33 vs 16%). The aesthetic rating of results was 4.6/5 for
      Keyhole and 3.7/5 for DIFNG. Conclusions: Safe and aesthetically pleasing results
      were achieved using this simplified algorithm. Experience with FTM techniques can
      decrease complication and reoperation rates over time. Level of Evidence: 3.

PMID- 29040350
TI  - Editorial: Innovations in Study Design-A Call for Creative Solutions.

PMID- 29040352
TI  - Preoperative Respiratory Physiotherapy in Abdominoplasty Patients.
AB  - Background: After abdominoplasty, patients experience decreased ventilatory
      function and increased intra-abdominal pressure (IAP). Breathing exercises are
      used during the pre- and postoperative periods of several abdominal surgeries to
      prevent or minimize postoperative complications. Objectives: The aim of this
      study was to assess the effect of preoperative respiratory physiotherapy on the
      outcome of abdominoplasty patients. Methods: Thirty-three patients were divided
      into 2 groups. The control group (n = 18) received no preoperative intervention.
      The intervention group (n = 15) performed breathing exercises during the
      preoperative period, including incentive spirometry, diaphragmatic breathing,
      shortened expiration, and sustained maximal inspiration. Respiratory
      physiotherapy started one week before surgery. Breathing exercises were performed
      daily. They were performed 3 times weekly in the presence of a physiotherapist
      and patients were instructed to carry on the exercises at home on days without
      physiotherapy sessions for three sets of 20 repetitions each. Patients were
      assessed by spirometry and IAP measurements. Results: No significant difference
      in spirometry was found between groups. However, patients in the intervention
      group had lower IAP at the start of surgery and at all time points (P = 0.010)
      compared with controls. Conclusions: Preoperative respiratory physiotherapy had
      no impact on spirometry, but may have contributed to reduce IAP intraoperatively.
      Level of Evidence 2: 

PMID- 29040351
TI  - Oxytocin Genotype Moderates the Impact of Social Support on Psychiatric Distress
      in Alcohol-Dependent Patients.
AB  - Aims: The social environment strongly influences individual mental health.
      Individuals with strong social support systems tend to experience higher levels
      of well-being, lower levels of psychological distress and exhibit fewer
      psychiatric symptoms. However, there is a significant degree of individual
      variability as to the extent to which social support is beneficial to overall
      mental health. From a neurobiological perspective, it is suggested that the
      social hormone, oxytocin, may moderate the favorable effects of social
      interaction. To explore this possibility, we evaluated oxytocin genotype, social
      support and psychological health in a group of individuals diagnosed with DSM-IV
      alcohol dependence. Methods: The associations between OXT genotype, social
      support and psychological health were analyzed in data from 269 adults diagnosed
      with DSM-IV alcohol dependence (25% female) admitted into residential treatment
      programs and outpatient centers in Warsaw, Poland. Results: In line with past
      observations, we noted that psychiatric distress scores were negatively
      correlated with social support. Extending these observations, we uncovered a
      significant moderating effect of OXT genotype (rs2740210) on the relationship
      between social support and psychiatric distress. While G carriers displayed the
      predicted negative relationship between social support and psychiatric distress,
      T homozygotes failed to exhibit such a relationship. Conclusion: Genetically
      driven variation in oxytocin system functioning may influence the degree to which
      the beneficial effects of social support are felt in this population. These
      results have direct clinical relevance as enhancing social engagement to improve
      mental health may prove to be a less effective strategy in some patients owing to
      intrinsic factors. Short summary: The associations between oxytocin genotype,
      social support, and psychological health were analyzed in data from 269 adults
      diagnosed with DSM-IV alcohol dependence. A significant moderating effect of OXT
      genotype (rs2740210) on the relationship between social support and psychiatric
      distress was detected.

PMID- 29040353
TI  - Sociodemographic Differences Between Alcohol Use and Sickness Absence: Pooled
      Analysis of Four Cohort Studies.
AB  - Aims: We examined differences in sickness absence in relation to at-risk drinking
      and abstinence, taking into account potential changes in consumption. Methods: We
      used individual-participant data (n = 46,514) from four prospective cohort
      studies from Finland, France and the UK. Participants responded to a survey on
      alcohol use at two time points 4-6 years apart, and were linked to records of
      sickness absence for an ~6-year follow-up after the latter survey. Abstainers
      were those reporting no alcohol use in either survey. At-risk drinkers at T1 were
      labelled as 'former', at-risk drinkers at T2 as 'current' and at-risk drinkers at
      both times as 'consistent' at-risk drinkers. The reference group was low-risk
      drinkers at both times. Study-specific analyses were stratified by sex and
      socioeconomic status (SES) and the estimates were pooled using meta-analysis.
      Results: Among men (n = 17,285), abstainers (6%), former (5%), current (5%) and
      consistent (7%) at-risk drinkers had an increased risk of sickness absence
      compared with consistent low-risk drinkers (77%). Among women (n = 29,229), only
      abstainers (12%) had a higher risk of sickness absence compared to consistent low
      risk drinkers (74%). After adjustment for lifestyle and health, abstaining from
      alcohol was associated with sickness absence among people with intermediate and
      high SES, but not among people with low SES. Conclusions: The U-shaped alcohol
      use-sickness absence association is more consistent in men than women. Abstinence
      is a risk factor for sickness absence among people with higher rather than lower
      SES. Healthy worker effect and health selection may partly explain the observed
      differences. Short summary: In a pooled analysis from four cohort studies from
      three European countries, we demonstrated a U-shaped association between alcohol
      use and sickness absence, particularly among men. Abstinence from alcohol was
      associated with increased sickness absenteeism among both sexes and across
      socioeconomic strata, except those with low SES.

PMID- 29040354
TI  - Commentary on: Preoperative Respiratory Physiotherapy in Abdominoplasty Patients.

PMID- 29040355
TI  - Commentary on: Outcome After Breast Reduction Considering Body Mass Index and
      Resection Amount.

PMID- 29040356
TI  - Commentary on: Plastic Surgery-Related Hashtag Utilization on Instagram:
      Implications for Education and Marketing.

PMID- 29040357
TI  - Environmental Context Influences Visual Attention to Responsible Drinking
      Messages.
AB  - Aims: Responsible drinking messages (RDMs) are used as a key tool to reduce
      alcohol-related harms. A common form of RDM is in a poster format displayed in
      places such as bars, bus stops and toilet cubicles. However, evidence for the
      effectiveness of RDMs remains limited. Moreover, it is not known how
      environmental contexts (e.g. the number of alcohol-related cues in the
      environment) impact how such RDMs are interacted with, nor how this in turn
      affects their efficacy. Methods: One hundred participants completed a pseudo
      taste preference task in either in a bar laboratory (alcohol cue rich
      environmental context) or a traditional laboratory. The walls of the laboratory
      displayed either RDM or control posters during this task and eye tracking was
      used to assess participant attention to the posters. Results: Participants looked
      at the RDM posters less in the bar laboratory where the environmental context is
      rich in alcohol cues compared to a traditional laboratory where alcohol cues are
      sparse. Neither poster type or environmental context affected the amount of
      'alcohol' consumed and the amount of visual attention given to RDMs was unrelated
      to the amount of 'alcohol' consumed. Conclusions: These findings provide
      experimental evidence that RDMs do not influence drinking behaviour in the
      direction intended (reduced consumption in situ). In addition, locating RDMs in
      alcohol-cue rich environments may result in sub-optimal behavioural responses to
      the RDM materials (e.g. visual attention to content). To maximize the potential
      impact of RDMs, the optimal location for RDMs is in environments where pre
      existing alcohol cues are sparse to non-existent. Short Summary: Responsible
      drinking messages (RDMs) aim to reduce alcohol consumption, however, the findings
      of this study show that they may not influence in situ consumption. These
      findings also suggest that the optimal location for RDMs is in environments with
      few or no other alcohol-related cues.

PMID- 29040358
TI  - Tissue Expansion Using Hyaluronic Acid Filler for Single-Stage Ear
      Reconstruction: A Novel Concept for Difficult Areas.
AB  - Background: Auricular reconstruction is one of the most challenging procedures in
      plastic surgery. An adequate skin envelope is essential for cartilage framework
      coverage, yet few good options exist without additional surgery. We propose a
      novel method for minimally invasive tissue expansion, using hyaluronic acid (HA)
      filler to allow for single-stage ear reconstruction. Objectives: To introduce the
      novel concept of HA filler for tissue expansion in ear reconstruction, and as an
      alternative to traditional expansion techniques. Methods: Macrolane is a large
      particle HA gel developed for large volume restoration. Expansion of the non-hair
      bearing mastoid skin was performed in our clinic weekly or every other week.
      Final expansion was completed one week prior to reconstructive surgery. Tissue
      from one patient's expanded pocket was sent for histological analysis. Results:
      Ten patients underwent single-stage auricular reconstruction with preoperative
      expansion. Injection sessions ranged from 7 to 13 (mean, 9.7). Mean injected
      volume per session was 2.03 mL per patient, for an average total of 19.8 mL
      (range, 14.5-30 mL). There were no major complications. One minor complication
      required removal of exposed wire from the antihelix in the office. Hematoxylin
      and eosin stain revealed similar histology to that seen with traditional
      expanders. Conclusions: This novel expansion technique using serial HA injections
      allowed for optimized skin coverage in single-stage ear reconstruction. The
      concept of tissue expansion using HA filler is a new frontier for research that
      may be applicable to other arenas of reconstruction. Level of Evidence: 4.

PMID- 29040359
TI  - A rank-based algorithm of differential expression analysis for small cell line
      data with statistical control.
AB  - To detect differentially expressed genes (DEGs) in small-scale cell line
      experiments, usually with only two or three technical replicates for each state,
      the commonly used statistical methods such as significance analysis of
      microarrays (SAM), limma and RankProd (RP) lack statistical power, while the fold
      change method lacks any statistical control. In this study, we demonstrated that
      the within-sample relative expression orderings (REOs) of gene pairs were highly
      stable among technical replicates of a cell line but often widely disrupted after
      certain treatments such like gene knockdown, gene transfection and drug
      treatment. Based on this finding, we customized the RankComp algorithm,
      previously designed for individualized differential expression analysis through
      REO comparison, to identify DEGs with certain statistical control for small-scale
      cell line data. In both simulated and real data, the new algorithm, named
      CellComp, exhibited high precision with much higher sensitivity than the original
      RankComp, SAM, limma and RP methods. Therefore, CellComp provides an efficient
      tool for analyzing small-scale cell line data.

PMID- 29040360
TI  - Elucidating the editome: bioinformatics approaches for RNA editing detection.
AB  - RNA editing is a widespread co/posttranscriptional mechanism affecting primary
      RNAs by specific nucleotide modifications, which plays relevant roles in
      molecular processes including regulation of gene expression and/or the processing
      of noncoding RNAs. In recent years, the detection of editing sites has been
      improved through the availability of high-throughput RNA sequencing (RNA-Seq)
      technologies. Accurate bioinformatics pipelines are essential for the analysis of
      next-generation sequencing (NGS) data to ensure the correct identification of
      edited sites. Several pipelines, using various read mappers and variant callers
      with a wide range of adjustable parameters, are available for the detection of
      RNA editing events. In this review, we discuss some of the most recent and
      popular tools and provide guidelines for RNA-Seq data generation and analysis for
      the detection of RNA editing in massive transcriptome data. Using simulated and
      real data sets, we provide an overview of their behavior, emphasizing the fact
      that the RNA editing detection in NGS data sets remains a challenging task.

PMID- 29040361
TI  - Commentary on: Labia Majora Augmentation: A Systematic Review of the Literature.

PMID- 29040362
TI  - Prediction of protein-protein interactions between fungus (Magnaporthe grisea)
      and rice (Oryza sativa L.).
AB  - Rice blast disease caused by the fungus Magnaporthe grisea (M. grisea) is one of
      the most serious diseases for the cultivated rice Oryza sativa (O. sativa). A key
      factor causing rice blast disease and defense might be protein-protein
      interactions (PPIs) between rice and fungus. In this research, we have developed
      a computational pipeline to predict PPIs between blast fungus and rice. After
      cross-prediction by interolog-based and domain-based method, we achieved 532
      potential PPIs between 27 fungus proteins and 236 rice proteins. Accuracy of
      jackknife test, 10-fold cross-validation test and independent test for these PPIs
      were 90.43, 93.85 and 84.67%, respectively, by using support vector machine
      classification method. Meanwhile, the pathogenic genes of blast fungus were
      enriched in the predicted PPIs network when compared with 1000 random interaction
      networks. The rice regulatory network was downloaded and divided into 228
      subnetworks with over six nodes, and the top seven subnetworks affected by blast
      fungus through PPIs were investigated. The results indicated that 34 upregulated
      and 12 downregulated master regulators in rice interacting with the fungus
      proteins in response to the infection of blast fungus. The common master
      regulators in rice in response to the infection of M. grisea, Xanthomonas oryzae
      pv.oryzae and rice stripe virus were analyzed. The ubiquitin proteasome pathway
      was the common pathway in rice regulated by these three pathogens, while
      apoptosis signaling pathway was induced by fungus and bacteria. In summary, the
      results in this article provide insight into the process of blast fungus
      infection.

PMID- 29040363
TI  - Establishing Milestones for Facial Injectables in Plastic Surgery Residency
      Training: Four-Year Follow-Up.

PMID- 29040364
TI  - Preliminary 3-Year Evaluation of Experience With SilkSurface and VelvetSurface
      Motiva Silicone Breast Implants: A Single-Center Experience With 5813 Consecutive
      Breast Augmentation Cases.
AB  - Background: Silicone breast implants have been in use for breast augmentation for
      more than 50 years, but technological innovation has been lacking in implant
      design until recently. Objectives: This study was designed to evaluate the
      complication and reoperation rates following breast augmentation utilizing the
      Motiva silicone breast implants. Methods: This retrospective study evaluated the
      safety of Motiva implants in 5813 consecutive cases of breast augmentation.
      Implants with two different textured surfaces were evaluated: SilkSurface
      (nanotextured) and VelvetSurface (micro-textured). Results: Implants were placed
      between April 2013 and April 2016. A total of 44 complications were reported,
      with an overall complication rate of 0.76%, and the rate of reoperation was 0.76%
      over an interval of 3 years. There were no late complications and no cases of
      primary capsular contracture. No differences in complication rates were observed
      because of the implant date. However, among patients who received implants 300 to
      499 cc in volume, complication rates were significantly lower with SilkSurface
      compared with VelvetSurface implants. Advanced statistical analysis supported the
      validity of the low complication rate reported in this study. Conclusions:
      Overall, these findings suggest that Motiva silicone breast implants are
      associated with very low rates of complication and reoperation, and that the nano
      textured SilkSurface implant is associated with fewer complications than micro
      textured implants. Level of Evidence 3: 

PMID- 29040366
TI  - Origami Model for Central Wedge Labiaplasty: A Simple Educational Model with
      Video Tutorial.

PMID- 29040365
TI  - Role of the Akt/mTOR signaling pathway in human papillomavirus-associated nasal
      and sinonasal inverted papilloma.
AB  - Nasal and sinonasal inverted papilloma (NSIP) is a benign tumor in which surface
      epithelial cells grow downward into the underlying supportive tissue with varying
      degrees of metaplasia. Human papillomavirus (HPV) has been proposed as the causal
      agent in the pathogenesis of this disease. Many studies have shown that HPV can
      activate the Akt/mechanistic target of rapamycin (mTOR) signaling pathway, but
      the role of this pathway in HPV-associated NSIP is largely unknown. In this
      study, we enrolled 40 control tissue samples and 80 NSIP tissue samples. HPV
      genotyping showed that 47 of the 80 examined cases of NSIP were HPV-positive
      (58.8%), and the most common subtype was HPV11 (20/53, 37.7%). The
      immunohistochemistry showed statistically significant differences in
      phosphorylated Akt and phosphorylated S6 ribosomal protein staining among control
      samples, HPV-positive NSIP and HPV-negative NSIP. The HPV11 L1-L2 plasmid
      increased the proliferation of normal human nasopharyngeal epithelial NP69-SV40T
      cells and human nasopharyngeal cancer CNE1 cells. Meanwhile, rapamycin, an mTOR
      inhibitor, reversed the increased cell proliferation induced by the HPV11 L1-L2
      plasmid. Western blot analysis showed that Akt/mTOR/S6 were overexpressed in NP69
      SV40T cells and CNE1 cells infected with the HPV11 L1-L2 plasmid. These data
      demonstrate that HPV promotes cell proliferation through the Akt/mTOR signaling
      pathway in NSIP.

PMID- 29040367
TI  - Forehead Lift Using Botulinum Toxin.
AB  - Background: The principle of dynamic muscular activity affecting eyebrow height
      and shape is well known. We postulate that similarly, dynamics of the fronto
      galea-occipital muscles affect forehead height. Objectives: To present a forehead
      lift technique using Botulinum toxin injection and evaluate its clinical efficacy
      and safety. Methods: Twenty-nine female patients comprised the study group. Forty
      units of prepared abobutolinumtoxinA (Dysport, 10 U/0.05 mL) were injected into 4
      points in the hair-bearing scalp, simulating the points of frontalis origin. The
      glabella and forehead regions were treated with 50 U each. Standard photographs
      and measurements were taken before and at 2 weeks following treatment. Forehead
      height was measured bilaterally drawing a vertical line from mid-pupil to frontal
      hairline (MPFH) and from medial canthus to frontal hairline (MCFH). We assessed
      outcome differences in patients with low vs high forehead (cutoff value 5.5 cm
      forehead height). Results: Mean age was 48 years (range, 29-66 years). Two weeks
      following treatment, mean frontal height had increased significantly in all
      measurement points (MCFH right: 4.1 +/- 1.8 mm, MCFH left 4.4 +/- 1.8 mm, MPFH
      right 4.4 +/- 2.0 mm, MPFH left 4.7 +/- 2.3 mm; P <0.001). Low forehead subgroup
      achieved significantly higher forehead lift compared with high forehead subgroup
      both in MCFH (6.9% +/- 2.0% vs 5.3% +/- 2.2%, P = 0.043) and MPFH (8.6% +/- 2.5%
      vs 5.7% +/- 2.6%, P = 0.008). No adverse events were documented in any
      participant. Conclusions: Botulinum toxin type A injection into frontalis origin
      can effectively and safely extend forehead height in selected patients. The
      effect of this technique is greater on patients with low foreheads. Level of
      Evidence 4: 

PMID- 29040368
TI  - Commentary on: Heterogeneity in Body Contouring Outcomes Based Research: The
      Pittsburgh Body Contouring Complication Reporting System.

PMID- 29040369
TI  - Does the Supine Position Affect the Nasal Profile in Rhinoplasty Patients? A
      Comparison of Nasal Anthropometric Measurements in Different Body Positions.
AB  - Background: Rhinoplasty surgeons are aware that the nasal profile differs
      according to body position, namely, the erect position in the consultation room
      vs the supine position on the operating table. It is not clear whether this
      difference is caused by an optical illusion or skin laxity due to positional
      change. Objectives: To evaluate anthropometric measurements of the nose with
      different body positions and determine whether the supine position affects the
      nasal profile. Methods: In this retrospective study, 103 patients who underwent
      primary rhinoplasty were enrolled. Preoperatively, all patients underwent lateral
      cephalography in the erect position, and facial computed tomography (CT), in the
      supine position. We measured four nasal anthropometric parameters (the
      nasofrontal, nasolabial, and nasomental angles, and Simon's ratio) on lateral
      cephalograms and facial CT images, and compared these parameters between the two
      body positions. Results: The nasofrontal angle was greater on facial CT than on
      cephalograms (P < 0.01). This difference was not related to age, sex, or body
      mass index (P > 0.05 each). We found no significant difference (P > 0.05) between
      the two positions in the nasolabial angle, nasomental angle, or Simon's ratio.
      Conclusions: The supine position does affect the nasal profile, especially in the
      radix area. Surgeons need to consider this difference in patients undergoing
      rhinoplasty. Level of Evidence: 2.

PMID- 29040371
TI  - Commentary on: Demystifying the "July Effect" in Plastic Surgery: A Multi
      Institutional Study.

PMID- 29040370
TI  - Long-Term Safety of Textured and Smooth Breast Implants.
AB  - In this review, the authors provide a 20-year review and comparison of implant
      options and describe the evolution of breast implant surface textures; compare
      available implant surfaces; present long-term safety data from the 10-year US
      based Core clinical studies; list the key benefits and risks associated with
      smooth and textured implants; and provide perspectives on breast implant
      associated anaplastic large cell lymphoma (BIA-ALCL). The authors explore the key
      benefits and risks associated with all available devices so that optimal and safe
      patient outcomes can be achieved.

PMID- 29040372
TI  - Response to "Commentary on: Gluteal Augmentation Techniques: A Comprehensive
      Literature Review".

PMID- 29040373
TI  - Nonsurgical Vulvovaginal Rejuvenation With Radiofrequency and Laser Devices: A
      Literature Review and Comprehensive Update for Aesthetic Surgeons.
AB  - Nonsurgical vulvovaginal rejuvenation (NVR) is growing in popularity as a
      treatment for restoration of youthful female genitalia. Numerous radiofrequency
      (RF) and laser devices have entered the market claiming improvement in vaginal
      laxity and genitourinary syndrome of menopause. There is a paucity of evidence
      existing concerning the effectiveness of these devices for both pre- and
      postmenopausal women with laxity and/or atrophy at the histologic and clinical
      level. Therefore, the goal of this review is to scrutinize the peer-reviewed data
      on NVR with RF and laser devices, identify gaps in existing literature, and
      propose opportunities for further investigation.

PMID- 29040374
TI  - Beyond similarity assessment: selecting the optimal model for sequence alignment
      via the Factorized Asymptotic Bayesian algorithm.
AB  - Motivation: Pair Hidden Markov Models (PHMMs) are probabilistic models used for
      pairwise sequence alignment, a quintessential problem in bioinformatics. PHMMs
      include three types of hidden states: match, insertion and deletion. Most
      previous studies have used one or two hidden states for each PHMM state type.
      However, few studies have examined the number of states suitable for representing
      sequence data or improving alignment accuracy. Results: We developed a novel
      method to select superior models (including the number of hidden states) for
      PHMM. Our method selects models with the highest posterior probability using
      Factorized Information Criterion, which is widely utilized in model selection for
      probabilistic models with hidden variables. Our simulations indicated that this
      method has excellent model selection capabilities with slightly improved
      alignment accuracy. We applied our method to DNA datasets from 5 and 28 species,
      ultimately selecting more complex models than those used in previous studies.
      Availability and implementation: The software is available at
      https://github.com/bigsea-t/fab-phmm. Contact: mhamada@waseda.jp. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29040375
TI  - Multitasking: So You Think You're a Pro?

PMID- 29040376
TI  - AEGS: identifying aberrantly expressed gene sets for differential variability
      analysis.
AB  - Motivation: In gene expression studies, differential expression (DE) analysis has
      been widely used to identify genes with shifted expression mean between groups.
      Recently, differential variability (DV) analysis has been increasingly applied as
      analyzing changed expression variability (e.g. the changes in expression
      variance) between groups may reveal underlying genetic heterogeneity and
      undetected interactions, which has great implications in many fields of biology.
      An easy-to-use tool for DV analysis is needed. Results: We develop AEGS for DV
      analysis, to identify aberrantly expressed gene sets in diseased cases but not in
      controls. AEGS can rank individual genes in an aberrantly expressed gene set by
      each gene's relative contribution to the total degree of aberrant expression,
      prioritizing top genes. AEGS can be used for discovering gene sets with disease
      specific expression variability changes. Availability and implementation: AEGS
      web server is accessible at http://bmi.xmu.edu.cn:8003/AEGS, where a stand-alone
      AEGS application can also be downloaded. Contact: glji@xmu.edu.cn.

PMID- 29040377
TI  - Safest Practices for Autologous Buttock Augmentation With Fat Grafting Using a
      Roller Pump Injection Technique.
AB  - Background: Autologous buttock augmentation with fat grafting has emerged as one
      of the preeminent modalities for body contouring employed by plastic surgeons
      today. Since 2009, we have used the roller pump injection technique. Objectives:
      This procedure can be performed safely without specialized equipment and
      eliminates the tasks of manual graft preparation and injection. We describe our
      technique and standard safety measures. The anatomy of and complications
      associated with liposuction and fat grafting were recorded and reviewed. Methods:
      Retrospective chart review of 916 patients who underwent autologous buttock
      augmentation by this method from February 2009 to November 2016 was performed.
      All procedures were performed under general anesthesia at the same surgical
      center. Liposuction was performed and using a roller pump, the fat layer was
      propelled through an open-ended cannula into the recipient site. Results: Mean
      volume of fat removed and fat grafted in each patient was 3156 mL and 1807 mL per
      patient, respectively. There were complications in 13 patients for a rate of 1.4%
      with 10 (1.1%) related to fat grafting. Fourteen patients (1.5%) had subsequent
      procedures for volume and four patients (0.44%) for asymmetry. There were no
      venous thrombolic events, fat embolic events, or deaths. Conclusions: The roller
      pump injection technique for buttock augmentation with fat grafting is safe and
      efficient. This technique minimizes preparatory effort and does not require
      additional equipment. We were unable to identify variables associated with
      complication risk due to the power of this study and the low percentage of
      complications. Level of Evidence 4: 

PMID- 29040378
TI  - Plastic Surgery-Related Hashtag Utilization on Instagram: Implications for
      Education and Marketing.
AB  - Background: Recent data suggest patients are seeking aesthetic surgery to improve
      their appearance on Instagram and other social media. Despite the rising
      influence of Instagram in plastic surgery, few academic publications address
      Instagram, let alone evaluate its utilization in plastic surgery. Objectives: We
      set out to answer the following three questions: 1) what plastic surgery-related
      content is being posted to Instagram; 2) who is posting this content; and 3) what
      specific hashtags are they using? Methods: Our study queried 21 Instagram plastic
      surgery-related hashtags. Content analysis was used to qualitatively evaluate
      each of the nine "top" posts associated with each hashtag (189 posts). Duplicate
      posts and those not relevant to plastic surgery were excluded. Results: A total
      of 1,789,270 posts utilized the 21 hashtags sampled in this study. Of the top 189
      posts for these 21 queried hashtags, 163 posts met inclusion criteria. Plastic
      surgeons eligible for membership in American Society for Aesthetic Plastic
      Surgery (ASAPS) accounted for only 17.8% of top posts, whereas noneligible
      physicians accounted for 26.4%. All nonplastic surgery trained physicians
      marketed themselves as "cosmetic surgeons." Nine top posts (5.5%) were by
      nonphysicians, including dentists, spas with no associated physician, and a hair
      salon. The majority of these posts were self-promotional (67.1%) as opposed to
      educational (32.9%). Board-certified plastic surgeons were significantly more
      likely to post educational content to Instagram as compared to nonplastic
      surgeons (62.1% vs 38.1%, P = 0.02). Conclusions: ASAPS eligible board-certified
      plastic surgeons are underrepresented amongst physicians posting top plastic
      surgery-related content to Instagram.

PMID- 29040380
TI  - A historical perspective on some "new" discoveries on spermatogenesis from the
      laboratory of Enrico Sertoli in 1878.

PMID- 29040379
TI  - Contrasting evolutionary processes during Quaternary climatic changes and
      historical orogenies: a case study of the Japanese endemic primroses Primula
      sect. Reinii.
AB  - Background and Aims: Recent biogeographic studies have illustrated that
      Quaternary climatic changes and historical orogenies have driven the development
      of high levels of biodiversity. In this context, phylogenetic niche conservatism
      may play a role as a major precursor of allopatric speciation. However, the
      effects of niche evolution on the diversification patterns of plant species under
      rapid habitat changes are still unknown. Here, Primula section Reinii, one of the
      few primroses endemic to the Japanese Archipelago, was investigated. This study
      aimed to clarify the phylogenetic position and relationships of section Reinii,
      interpret the biogeographic and diversification patterns of this group and gain a
      better understanding of the role of climatic niche evolution in the Japanese
      endemic primroses. Methods: Dated phylogeny for Primula section Reinii is
      presented based on the sequences of six chloroplast genes and one nuclear gene.
      Biogeographic history was reconstructed using statistical dispersal-vicariance
      analysis. Macro-evolutionary modelling of the climatic niche was combined with
      biogeographic inferences. Key Results: Section Reinii was shown to be
      monophyletic based on chloroplast and nuclear sequences. Fossil-calibrated dating
      analysis estimated that this section diverged from its sister taxon, sect.
      Cortusoides, around 1.82 million years ago, and intraspecific diversification
      occurred within the last million years. This time frame was characterized by
      Quaternary climatic oscillations and uplift of high mountains in Japan.
      Biogeographic inference suggested that this section originated at the northern
      end of the Japanese Archipelago and then dispersed southward to other islands.
      Models of climatic niche evolution indicated that the closely related species P.
      reinii and P. tosanensis have contrasting niche optima and rates of niche
      evolution. Conclusion: Our results highlight that spatiotemporal heterogeneity in
      the Japanese islands may play a significant role in the biogeographic history of
      Japanese endemic primroses. Contrasting evolutionary processes found in closely
      related species illustrate the effects of climatic niche evolution on species'
      diversification patterns.

PMID- 29040381
TI  - The CUG-translated WT1, not AUG-WT1, is an oncogene.
AB  - The Wilms' tumor 1 (WT1) gene is believed to act as a canonical tumor suppressor.
      However, it has also been reported to function as an oncogene. Germline WT1
      deletion is associated with Wilms' tumor, and exogenous WT1 cDNA introduction
      into cells induces the transcriptional suppression of its oncogenic target genes.
      In contrast, high WT1 expression is associated with poor prognosis in patients
      with various cancers. Why WT1 acts as a tumor suppressor under certain conditions
      but as an oncogene under other conditions is unknown. Here, we report that CUG
      initiation site for WT1 protein synthesis (CUG)-translated WT1 (cugWT1), an N
      terminally extended form of canonical AUG initiation site for WT1 protein
      synthesis (AUG)-translated WT1 (augWT1), was overexpressed in most cancer cell
      lines and cancer tissues and functioned as an oncogene, whereas the classical
      augWT1 acted as a tumor suppressor as reported previously and inhibited the
      function of cugWT1. Translation of cugWT1 is initiated from a CUG codon upstream
      and in-frame with the coding region of augWT1. cugWT1 induced cell transformation
      and increased the gene expression of c-myc, bcl-2 and egfr, whereas
      overexpression of augWT1 repressed colony formation of cancer cells and inhibited
      the expression of the same target genes by recruiting histone deacetylase 1
      (HDAC1). In addition, we found that protein kinase B (AKT)-phosphorylated cugWT1
      on Ser62 and protected cugWT1 from proteasomal degradation induced by the F
      box/WD repeat-containing protein 8 (FBXW8). These results provide an important
      breakthrough in the field of cancer biology and contribute significantly to the
      resolution of the chameleon function of WT1.

PMID- 29040383
TI  - Beyond the matrix: MMP2 as critical regulator of inflammation-mediated vascular
      dysfunction.

PMID- 29040382
TI  - Generalized correlation measure using count statistics for gene expression data
      with ordered samples.
AB  - Motivation: Capturing association patterns in gene expression levels under
      different conditions or time points is important for inferring gene regulatory
      interactions. In practice, temporal changes in gene expression may result in
      complex association patterns that require more sophisticated detection methods
      than simple correlation measures. For instance, the effect of regulation may lead
      to time-lagged associations and interactions local to a subset of samples.
      Furthermore, expression profiles of interest may not be aligned or directly
      comparable (e.g. gene expression profiles from two species). Results: We propose
      a count statistic for measuring association between pairs of gene expression
      profiles consisting of ordered samples (e.g. time-course), where correlation may
      only exist locally in subsequences separated by a position shift. The statistic
      is simple and fast to compute, and we illustrate its use in two applications. In
      a cross-species comparison of developmental gene expression levels, we show our
      method not only measures association of gene expressions between the two species,
      but also provides alignment between different developmental stages. In the second
      application, we applied our statistic to expression profiles from two distinct
      phenotypic conditions, where the samples in each profile are ordered by the
      associated phenotypic values. The detected associations can be useful in building
      correspondence between gene association networks under different phenotypes. On
      the theoretical side, we provide asymptotic distributions of the statistic for
      different regions of the parameter space and test its power on simulated data.
      Availability and implementation: The code used to perform the analysis is
      available as part of the Supplementary Material. Contact: msw@usc.edu or
      hhuang@stat.berkeley.edu. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29040384
TI  - SELANSI: a toolbox for simulation of stochastic gene regulatory networks.
AB  - Motivation: Gene regulation is inherently stochastic. In many applications
      concerning Systems and Synthetic Biology such as the reverse engineering and the
      de novo design of genetic circuits, stochastic effects (yet potentially crucial)
      are often neglected due to the high computational cost of stochastic simulations.
      With advances in these fields there is an increasing need of tools providing
      accurate approximations of the stochastic dynamics of gene regulatory networks
      (GRNs) with reduced computational effort. Results: This work presents SELANSI
      (SEmi-LAgrangian SImulation of GRNs), a software toolbox for the simulation of
      stochastic multidimensional gene regulatory networks. SELANSI exploits intrinsic
      structural properties of gene regulatory networks to accurately approximate the
      corresponding Chemical Master Equation with a partial integral differential
      equation that is solved by a semi-lagrangian method with high efficiency.
      Networks under consideration might involve multiple genes with self and cross
      regulations, in which genes can be regulated by different transcription factors.
      Moreover, the validity of the method is not restricted to a particular type of
      kinetics. The tool offers total flexibility regarding network topology, kinetics
      and parameterization, as well as simulation options. Availability and
      implementation: SELANSI runs under the MATLAB environment, and is available under
      GPLv3 license at https://sites.google.com/view/selansi. Contact:
      antonio@iim.csic.es.

PMID- 29040385
TI  - A benchmarking of workflows for detecting differential splicing and differential
      expression at isoform level in human RNA-seq studies.
AB  - Over the last few years, RNA-seq has been used to study alterations in
      alternative splicing related to several diseases. Bioinformatics workflows used
      to perform these studies can be divided into two groups, those finding changes in
      the absolute isoform expression and those studying differential splicing. Many
      computational methods for transcriptomics analysis have been developed, evaluated
      and compared; however, there are not enough reports of systematic and objective
      assessment of processing pipelines as a whole. Moreover, comparative studies have
      been performed considering separately the changes in absolute or relative isoform
      expression levels. Consequently, no consensus exists about the best practices and
      appropriate workflows to analyse alternative and differential splicing. To assist
      the adequate pipeline choice, we present here a benchmarking of nine commonly
      used workflows to detect differential isoform expression and splicing. We
      evaluated the workflows performance over different experimental scenarios where
      changes in absolute and relative isoform expression occurred simultaneously. In
      addition, the effect of the number of isoforms per gene, and the magnitude of the
      expression change over pipeline performances were also evaluated. Our results
      suggest that workflow performance is influenced by the number of replicates per
      condition and the conditions heterogeneity. In general, workflows based on
      DESeq2, DEXSeq, Limma and NOISeq performed well over a wide range of
      transcriptomics experiments. In particular, we suggest the use of workflows based
      on Limma when high precision is required, and DESeq2 and DEXseq pipelines to
      prioritize sensitivity. When several replicates per condition are available,
      NOISeq and Limma pipelines are indicated.

PMID- 29040386
TI  - Robust distributed lag models using data adaptive shrinkage.
AB  - Distributed lag models (DLMs) have been widely used in environmental epidemiology
      to quantify the lagged effects of air pollution on an outcome of interest such as
      mortality or cardiovascular events. Generally speaking, DLMs can be applied to
      time-series data where the current measure of an independent variable and its
      lagged measures collectively affect the current measure of a dependent variable.
      The corresponding distributed lag (DL) function represents the relationship
      between the lags and the coefficients of the lagged exposure variables. Common
      choices include polynomials and splines. On one hand, such a constrained DLM
      specifies the coefficients as a function of lags and reduces the number of
      parameters to be estimated; hence, higher efficiency can be achieved. On the
      other hand, under violation of the assumption about the DL function, effect
      estimates can be severely biased. In this article, we propose a general framework
      for shrinking coefficient estimates from an unconstrained DLM, that are unbiased
      but potentially inefficient, toward the coefficient estimates from a constrained
      DLM to achieve a bias-variance trade-off. The amount of shrinkage can be
      determined in various ways, and we explore several such methods: empirical Bayes
      type shrinkage, a hierarchical Bayes approach, and generalized ridge regression.
      We also consider a two-stage shrinkage approach that enforces the effect
      estimates to approach zero as lags increase. We contrast the various methods via
      an extensive simulation study and show that the shrinkage methods have better
      average performance across different scenarios in terms of mean squared error
      (MSE).We illustrate the methods by using data from the National Morbidity,
      Mortality, and Air Pollution Study (NMMAPS) to explore the association between
      PM$_{10}$, O$_3$, and SO$_2$ on three types of disease event counts in Chicago,
      IL, from 1987 to 2000.

PMID- 29040387
TI  - Commentary on: Female-to-Male Gender Affirming Top Surgery: A Single Surgeon's 15
      Year Retrospective Review and Treatment Algorithm.

PMID- 29040388
TI  - RNA structure interactions and ribonucleoprotein processes of the influenza A
      virus.
AB  - In one more years, we will 'celebrate' an exact centenary of the Spanish flu
      pandemic. With the rapid evolution of the influenza virus, the possibility of
      novel pandemic remains ever a concern. This review covers our current knowledge
      of the influenza A virus: on the role of RNA in translation, replication, what is
      known of the expressed proteins and the protein products generated from
      alternative splicing, and on the role of base pairing in RNA structure. We
      highlight the main events associated with viral entry into the cell, the
      transcription and replication process, an export of the viral genetic material
      from the nucleus and the final release of the virus. We discuss the observed
      potential roles of RNA secondary structure (the RNA base-pairing arrangement) and
      RNA/RNA interactions in this scheme.

PMID- 29040390
TI  - Robust and sparse correlation matrix estimation for the analysis of high
      dimensional genomics data.
AB  - Motivation: Microarray technology can be used to study the expression of
      thousands of genes across a number of different experimental conditions, usually
      hundreds. The underlying principle is that genes sharing similar expression
      patterns, across different samples, can be part of the same co-expression system,
      or they may share the same biological functions. Groups of genes are usually
      identified based on cluster analysis. Clustering methods rely on the similarity
      matrix between genes. A common choice to measure similarity is to compute the
      sample correlation matrix. Dimensionality reduction is another popular data
      analysis task which is also based on covariance/correlation matrix estimates.
      Unfortunately, covariance/correlation matrix estimation suffers from the
      intrinsic noise present in high-dimensional data. Sources of noise are: sampling
      variations, presents of outlying sample units, and the fact that in most cases
      the number of units is much larger than the number of genes. Results: In this
      paper, we propose a robust correlation matrix estimator that is regularized based
      on adaptive thresholding. The resulting method jointly tames the effects of the
      high-dimensionality, and data contamination. Computations are easy to implement
      and do not require hand tunings. Both simulated and real data are analyzed. A
      Monte Carlo experiment shows that the proposed method is capable of remarkable
      performances. Our correlation metric is more robust to outliers compared with the
      existing alternatives in two gene expression datasets. It is also shown how the
      regularization allows to automatically detect and filter spurious correlations.
      The same regularization is also extended to other less robust correlation
      measures. Finally, we apply the ARACNE algorithm on the SyNTreN gene expression
      data. Sensitivity and specificity of the reconstructed network is compared with
      the gold standard. We show that ARACNE performs better when it takes the proposed
      correlation matrix estimator as input. Availability and implementation: The R
      software is available at https://github.com/angy89/RobustSparseCorrelation.
      Contact: aserra@unisa.it or robtag@unisa.it. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29040389
TI  - The Antiepileptic Ketogenic Diet Alters Hippocampal Transporter Levels and
      Reduces Adiposity in Aged Rats.
AB  - Nutritional ketosis is induced by high fat/low carbohydrate dietary regimens,
      which produce high levels of circulating ketone bodies, shifting metabolism away
      from glucose utilization. While ketogenic diets (KD) were initially introduced to
      suppress seizures, they are garnering attention for their potential to treat a
      myriad of neurodegenerative and metabolic disorders that are associated with
      advanced age. The feasibility and physiological impact of implementing a long
      term KD in old animals, however, has not been systematically examined. In this
      study, young and aged rats consumed a calorically- and nutritionally-matched KD
      or control diet for 12 weeks. All KD-fed rats maintained higher levels of BHB and
      lower levels of glucose relative to controls. However, it took the aged rats
      longer to reach asymptotic levels of BHB compared to young animals. Moreover, KD
      fed rats had significantly less visceral white and brown adipose tissue than
      controls without a loss of lean mass. Interestingly, the KD led to significant
      alterations in protein levels of hippocampal transporters for monocarboxylates,
      glucose, and vesicular glutamate and gamma-aminobutyric acid. Most notably, the
      age-related decline in vesicular glutamate transporter expression was reversed by
      the KD. These data demonstrate the feasibility and potential benefits of KDs for
      treating age-associated neural dysfunction.

PMID- 29040391
TI  - Quantification of the Aesthetically Desirable Female Midface Position.
AB  - Background: The purpose of this study was to attempt to determine a reliable
      method of evaluating midface position. We assessed a novel parameter called
      WIZDOM (Width of the Interzygomatic Distance of the Midface) and its relationship
      to other facial metrics. Objectives: The goal was to evaluate midfacial position
      quantitatively in women by examining 2-dimensional photographs of a subset of
      women with idealized facial proportions. Methods: Three examiners analyzed stock
      photographs of nonsmiling female model faces. Numerous parameters were analyzed
      for each photograph, including: interpupillary distance, medial canthus (MC) to
      lip, brow length, WIZDOM, WIZDOM to MC, WIZDOM to hairline, WIZDOM to chin
      vertical, and lateral brow to WIZDOM. Meaningful relationships between various
      parameters were statistically analyzed. Examiner measurements were assessed for
      interobserver reliability. Results: Fifty-five female model photographs were
      included in the analysis. The average interpupillary distance was 59.2 mm +/-
      3.54 (range, 50.5-67.3 mm). The WIZDOM average was 108 mm +/- 5.81 (range, 93-127
      mm) and brow length was 107 mm +/- 5.87 (range, 96.7-124 mm). The difference
      between brow length and WIZDOM was not statistically different (P = 0.834). The
      interobserver reliability between the 3 examiners was excellent for all
      parameters (P < 0.01), ranging from 0.718 (WIZDOM-MC) to 0.993 (interpupillary
      distance). The WIZDOM measurement was reproducible with an interobserver
      coefficient of 0.939. Conclusions: WIZDOM can be used to quantify aesthetically
      desirable midfacial position in patients and can be used as a measurement to aid
      in assessment and as an ideal to achieve balanced aesthetic results in midface
      restorative procedures-lifting or volumization-in females.

PMID- 29040392
TI  - beta-Cypermethrin and its metabolite 3-phenoxybenzoic acid exhibit immunotoxicity
      in murine macrophages.
AB  - beta-Cypermethrin (beta-CYP), one of most important pyrethroids, is widely used
      to control insects, and has been detected in organisms, including human.
      Pyrethroids have been shown to pose neurotoxicity, hepatotoxicity, endocrine
      disruption and reproductive risks in mammals. However, research in immunotoxicity
      of pyrethroids, especially their metabolites, is limited. A common metabolite of
      pyrethroids is 3-phenoxybenzoic acid (3-PBA) in mammals. Thus, in this study, we
      evaluated the immunotoxicity of beta-CYP and 3-PBA in mouse macrophages, RAW
      264.7 cells. MTT assays showed that both beta-CYP and 3-PBA reduced cell
      viability in a concentration- and time-dependent manner. Flow cytometry with
      Annexin-V/PI staining demonstrated that both beta-CYP and 3-PBA induced RAW 264.7
      cell apoptosis. Furthermore, our results also showed that N-acetylcysteine
      partially blocked beta-CYP- and 3-PBA-induced cytotoxicity and apoptosis.
      Intrinsic apoptotic pathway was stimulated by both beta-CYP and 3-PBA exposure.
      In addition, we found that beta-CYP and 3-PBA inhibited mRNA levels of pro
      inflammatory cytokines with or without LPS stimulation. Phagocytosis assay showed
      that both beta-CYP and 3-PBA inhibited phagocytic ability of macrophages.
      Moreover, it was also found that both beta-CYP and 3-PBA increased reactive
      oxygen species (ROS) levels in RAW 264.7 cells. Accordingly, both beta-CYP and 3
      PBA were found to regulate the mRNA levels of oxidative stress-related genes in
      RAW 264.7 cells. Taken together, the results obtained in this study demonstrated
      that beta-CYP and 3-PBA may have immunotoxic effect on macrophages and that
      elevated ROS may underlie the mechanism. The present study will help to
      understand the health risks caused by beta-CYP and other pyrethroids.

PMID- 29040393
TI  - Extending the scope of Darwin's 'abominable mystery': integrative approaches to
      understanding angiosperm origins and species richness.
AB  - Background and aims: Angiosperms are the most species-rich group of land plants,
      but their origins and fast and intense diversification still require an
      explanation. Scope: Extending research scopes can broaden theoretical frameworks
      and lines of evidence that can lead to solving this 'abominable mystery'.
      Solutions lie in understanding evolutionary trends across taxa and throughout the
      Phanerozoic, and integration between hypotheses and ideas that are derived from
      multiple disciplines. Key Findings: Descriptions of evolutionary chronologies
      should integrate between molecular phylogenies, descriptive palaeontology and
      palaeoecology. New molecular chronologies open new avenues of research of
      possible Palaeozoic angiosperm ancestors and how they evolved during as many as
      200Myr until the emergence of true angiosperms. The idea that 'biodiversity
      creates biodiversity' requires evidence from past and present ecologies, with
      changes in herbivory and resource availability throughout the Phanerozoic
      appearing to be particularly promising. Conclusions: Promoting our understanding
      of angiosperm origins and diversification in particular, and the evolution of
      biodiversity in general, requires more profound understanding of the ecological
      past through integrating taxonomic, temporal and ecological scopes.

PMID- 29040394
TI  - Compound image segmentation of published biomedical figures.
AB  - Motivation: Images convey essential information in biomedical publications. As
      such, there is a growing interest within the bio-curation and the bio-databases
      communities, to store images within publications as evidence for biomedical
      processes and for experimental results. However, many of the images in biomedical
      publications are compound images consisting of multiple panels, where each
      individual panel potentially conveys a different type of information. Segmenting
      such images into constituent panels is an essential first step toward utilizing
      images. Results: In this article, we develop a new compound image segmentation
      system, FigSplit, which is based on Connected Component Analysis. To overcome
      shortcomings typically manifested by existing methods, we develop a quality
      assessment step for evaluating and modifying segmentations. Two methods are
      proposed to re-segment the images if the initial segmentation is inaccurate.
      Experimental results show the effectiveness of our method compared with other
      methods. Availability and implementation: The system is publicly available for
      use at: https://www.eecis.udel.edu/~compbio/FigSplit. The code is available upon
      request. Contact: shatkay@udel.edu. Supplementary information: Supplementary data
      are available online at Bioinformatics.

PMID- 29040395
TI  - Human Genome Sequencing at the Population Scale: A Primer on High-Throughput DNA
      Sequencing and Analysis.
AB  - Most human diseases have underlying genetic causes. To better understand the
      impact of genes on disease and its implications for medicine and public health,
      researchers have pursued methods for determining the sequences of individual
      genes, then all genes, and now complete human genomes. Massively parallel high
      throughput sequencing technology, where DNA is sheared into smaller pieces,
      sequenced, and then computationally reordered and analyzed, enables fast and
      affordable sequencing of full human genomes. As the price of sequencing continues
      to decline, more and more individuals are having their genomes sequenced. This
      may facilitate better population-level disease subtyping and characterization, as
      well as individual-level diagnosis and personalized treatment and prevention
      plans. In this review, we describe several massively parallel high-throughput DNA
      sequencing technologies and their associated strengths, limitations, and error
      modes, with a focus on applications in epidemiologic research and precision
      medicine. We detail the methods used to computationally process and interpret
      sequence data to inform medical or preventative action.

PMID- 29040396
TI  - Survival analysis with time-dependent covariates subject to missing data or
      measurement error: Multiple Imputation for Joint Modeling (MIJM).
AB  - Modern epidemiological studies collect data on time-varying individual-specific
      characteristics, such as body mass index and blood pressure. Incorporation of
      such time-dependent covariates in time-to-event models is of great interest, but
      raises some challenges. Of specific concern are measurement error, and the non
      synchronous updating of covariates across individuals, due for example to missing
      data. It is well known that in the presence of either of these issues the last
      observation carried forward (LOCF) approach traditionally used leads to bias.
      Joint models of longitudinal and time-to-event outcomes, developed recently,
      address these complexities by specifying a model for the joint distribution of
      all processes and are commonly fitted by maximum likelihood or Bayesian
      approaches. However, the adequate specification of the full joint distribution
      can be a challenging modeling task, especially with multiple longitudinal
      markers. In fact, most available software packages are unable to handle more than
      one marker and offer a restricted choice of survival models. We propose a two
      stage approach, Multiple Imputation for Joint Modeling (MIJM), to incorporate
      multiple time-dependent continuous covariates in the semi-parametric Cox and
      additive hazard models. Assuming a primary focus on the time-to-event model, the
      MIJM approach handles the joint distribution of the markers using multiple
      imputation by chained equations, a computationally convenient procedure that is
      widely available in mainstream statistical software. We developed an R package
      "survtd" that allows MIJM and other approaches in this manuscript to be applied
      easily, with just one call to its main function. A simulation study showed that
      MIJM performs well across a wide range of scenarios in terms of bias and coverage
      probability, particularly compared with LOCF, simpler two-stage approaches, and a
      Bayesian joint model. The Framingham Heart Study is used to illustrate the
      approach.

PMID- 29040397
TI  - Demystifying the "July Effect" in Plastic Surgery: A Multi-Institutional Study.
AB  - Background: The "July Effect" refers to a theoretical increase in complications
      that may occur with the influx of inexperienced interns and residents at the
      beginning of each academic year in July. Objectives: We endeavored to determine
      if a July Effect occurs in plastic surgery. Methods: Plastic surgery procedures
      were isolated from the National Surgical Quality Improvement Program registry.
      Cases involving residents were grouped as either having occurred within the first
      academic quarter (AQ1) or remaining year (AQ2-4). Groups were propensity matched
      using patient/operative factors and procedure type to account for baseline
      differences. Univariate and multivariate regression analyses assessed differences
      in overall complications, surgical and medical complications, individual
      complications, length of hospital stay, and operative time. A comparison group
      comprised of procedures without resident involvement was also analyzed. Results:
      There were 5967 cases with resident involvement, 5156 of which successfully
      matched. Both univariate and multivariate regression analyses revealed no
      significant differences between AQ1 and AQ2-4 in terms of overall, surgical,
      medical and individual complications, or length of hospital stay. There was a
      statistically significant, albeit not clinically significant, increase in
      operative time by 10 minutes per procedure during AQ1 in comparison to AQ2-4 (P =
      0.001). For procedures lacking resident participation, there were no differences
      between AQ1 and AQ2-4 in terms of these outcomes. Conclusions: A July Effect was
      not observed for plastic surgery procedures in our study, conceivably due to
      enhanced resident oversight and infrastructural safeguards. Patients electing to
      undergo plastic surgery early in the academic year can be reassured of their
      safety during this period.

PMID- 29040398
TI  - Correlation of Blood Pressure Variability as Measured By Clinic, Self-measurement
      at Home, and Ambulatory Blood Pressure Monitoring.
AB  - BACKGROUND: Blood pressure variability (BPV) has been postulated as a potential
      predictor of cardiovascular outcomes. No agreement exists as to which measurement
      method is best for BPV estimation. We attempt to assess the correlation between
      BPV obtained at the doctor's office, self-measurement at home (SMBP) and
      ambulatory BP monitoring (ABPM). METHODS: Eight weekly clinic BP measurements, 2
      SMBP series, and 1 24-hour ABPM recording were carried out in a sample of treated
      hypertensive patients. BPV was calculated using the SD, the "coefficient of
      variation" and the "average real variability." Determinants of short-, mid-, and
      long-term BPV (within each measurement method) were also calculated. The
      different BPV determinants were correlated "intramethod" and "intermethod" by
      linear regression test. RESULTS: For the 104 patients (66.5 +/- 7.7 years, 58.7%
      males), the ABPM BPV (SD, systolic/diastolic: 14.5 +/- 3.1/9.8 +/- 2.5 mm Hg) was
      higher than the SMBP (12.2 +/- 9.8/7.4 +/- 5.8 mm Hg; P < 0.001) and clinic BPV
      (10 +/- 8.9/5.9 +/- 4.9 mm Hg; P = 0.001). The main BPV correlation between
      methods was weak, with a maximum R2 = 0.17 (P < 0.001) between clinic and SMBP
      systolic BPV. The "intramethod" correlation of BPV yielded a maximum R2 = 0.21 (P
      < 0.001) between morning diastolic SMBP intershift/intermeans variability. The
      "intermethod" correlation of short-, mid-, and long-term BPV determinants was
      weak (maximum R2 = 0.22, P < 0.001, between clinic intraday variability/SMBP
      morning intershift variability). CONCLUSIONS: The "intramethod" and "intermethod"
      correlation between BPV determinants was weak or nonexistent, even when comparing
      determinants reflecting the same type of temporal BPV. Our data suggest that BPV
      reflects a heterogeneous phenomenon that strongly depends on the estimation
      method and the time period evaluated.

PMID- 29040399
TI  - Toward completion of the Earth's proteome: an update a decade later.
AB  - Protein databases are steadily growing driven by the spread of new more efficient
      sequencing techniques. This growth is dominated by an increase in redundancy
      (homologous proteins with various degrees of sequence similarity) and by the
      incapability to process and curate sequence entries as fast as they are created.
      To understand these trends and aid bioinformatic resources that might be
      compromised by the increasing size of the protein sequence databases, we have
      created a less-redundant protein data set. In parallel, we analyzed the evolution
      of protein sequence databases in terms of size and redundancy. While the
      SwissProt database has decelerated its growth mostly because of a focus on
      increasing the level of annotation of its sequences, its counterpart TrEMBL, much
      less limited by curation steps, is still in a phase of accelerated growth.
      However, we predict that before 2020, almost all entries deposited in UniProtKB
      will be homologous to known proteins. We propose that new sequencing projects can
      be made more useful if they are driven to sequencing voids, parts of the tree of
      life far from already sequenced species or model organisms. We show these voids
      are present in the Archaea and Eukarya domains of life. The approach to the
      certainty of the redundancy of new protein sequence entries leads to the
      consideration that most of the protein diversity on Earth has already been
      described, which we estimate to be of around 3.75 million proteins, revising down
      the prediction we did a decade ago.

PMID- 29040400
TI  - Treatment of Gastrocnemius Muscle Hypertrophy with Botulinum Toxin Injection
      Followed by Magnetic Resonance Imaging Assessment and 3-Dimensional Evaluation.
AB  - Background: Hypertrophy of the gastrocnemius muscle is considered to be a
      hindrance to lower leg beauty in the Asian aesthetic market. A noninvasive
      technique that has been gaining recognition involves botulinum toxin A injection;
      however, there are no proper guidelines or standardized protocols for the
      administration of botulinum toxin to correct gastrocnemius hypertrophy.
      Objectives: This study sought to determine the most effective botulinum toxin
      injection method for correcting the contour of the lower leg calf, as well as to
      determine the dose that can produce the maximum effect in meeting the demands of
      the physician and patient. Methods: Eighteen female patients aged between 18 and
      35 years were enrolled in this study from January 2015 to July 2015. Two
      injection methods were compared: (I) 48 injection points with a distance of 2 cm
      between every point; and (II) 10 injection points. Magnetic resonance imaging
      examinations were conducted at baseline prior to treatment and at one month and 6
      months after treatment. A 3-dimensional study was performed to analyze the
      volumetric changes. Results: The most effective and significant treatment method
      for hypertrophic gastrocnemius muscle was the 48-point method (scattering
      injection). Following injection, this method exhibited a significant level of
      satisfaction with outcome. Conclusions: Our study reveals that injection dosage
      and method have a strong relationship with achieving a better contouring result.
      Level of Evidence: 3.

PMID- 29040401
TI  - A Young Blood Environment Decreases Aging of Senile Mice Kidneys.
AB  - Whether changes in internal body environment affect kidney aging remains unclear.
      Specifically, it is unknown whether transplanted kidneys from older donors
      recover from tissue damage after placement in younger recipients. In this study,
      a parabiosis animal model was established to investigate the effects of a young
      internal body environment on aged kidneys. The animals were divided into six
      groups: young (Ycon) and old control (Ocon) groups, isochronic youth-youth group
      (Y-IP), elderly-elderly group (O-IP), and heterochronic youth (Y-HP) and elderly
      (O-HP) groups. After parabiosis, tubule and interstitial tissue scores in the O
      HP group were significantly lower than in the Ocon and O-IP groups. The
      expression of aging-related protein p16 and SA-beta-gal in the O-HP group was
      significantly reduced compared with the Ocon and O-IP groups. Autophagy factors
      Atg5 and LC3BII were significantly upregulated, whereas the expression of the
      autophagic degradation marker (P62) was significantly downregulated in the O-HP
      group compared with the Ocon and O-IP groups. With the same comparison, the
      positive cells of TUNEL staining and the expression of IL-6 and IL-1beta were
      significantly reduced, whereas the total/cleaved caspase-3 and total/pNF-kappaB
      were significantly increased in the O-HP group. The results demonstrated that a
      young blood environment significantly reduces kidney aging. These findings
      provide new evidence supporting an increase in the upper age limit for human
      kidney transplantation donors.

PMID- 29040402
TI  - Is postspinal hypotension a sign of impaired cardiac performance in the elderly?
      An observational mechanistic study.
AB  - Background: We have previously reported that stroke volume is reduced in a
      majority of elderly patients undergoing surgical repair of hip fracture before
      and after intrathecal injection of anaesthetic. We aimed to investigate these
      observations further in a prospective study of elderly patients undergoing
      elective hip or knee arthroplasty under spinal anaesthesia. Methods: Patients
      >=65 yr undergoing elective arthroplasty were monitored with LiDCOplusTM
      preoperatively (baseline), before and continuously for 45 min after spinal
      anaesthesia. Postspinal hypotension was defined as systolic blood pressure (bp) <
      100 mm Hg or > 30% decrease from baseline. Associations between post-spinal
      hypotension and haemodynamic changes before (i.e. between baseline and before
      injection) spinal anaesthesia were analysed by logistic regression analysis.
      Results: Twenty patients with a mean age of 74 (range 66-89) yr were included.
      Stroke volume index decreased by 14% (95% CI 9.3%-19%) before spinal anaesthesia.
      When patients were categorised according to post-spinal hypotension (Y/N) the
      patterns of haemodynamic changes differed. In the hypotensive patients, cardiac
      index progressively decreased whereas it increased initially in the non
      hypotensive patients. Reduction of cardiac index from baseline before spinal
      anaesthesia was associated with increased risk of hypotension: OR 0.79 (95% CI
      0.60, 0.91). The predictive value of reduced cardiac index was good (AUC under
      ROC curve 0.91). Conclusions: A decrease in cardiac output from baseline before
      spinal anaesthesia and an inability to increase it after induction may be
      important features of postspinal hypotension in elderly patients.

PMID- 29040403
TI  - Age-Related Changes in Temporal Processing of Rapidly-Presented Sound Sequences
      in the Macaque Auditory Cortex.
AB  - The mammalian auditory cortex is necessary to resolve temporal features in
      rapidly-changing sound streams. This capability is crucial for speech
      comprehension in humans and declines with normal aging. Nonhuman primate studies
      have revealed detrimental effects of normal aging on the auditory nervous system,
      and yet the underlying influence on temporal processing remains less well
      defined. Therefore, we recorded from the core and lateral belt areas of auditory
      cortex when awake young and old monkeys listened to tone-pip and noise-burst
      sound sequences. Elevated spontaneous and stimulus-driven activity were the
      hallmark characteristics in old monkeys. These old neurons showed isomorphic-like
      discharge patterns to stimulus envelopes, though their phase-locking was less
      precise. Functional preference in temporal coding between the core and belt
      existed in the young monkeys but was mostly absent in the old monkeys, in which
      old belt neurons showed core-like response profiles. Finally, the analysis of
      population activity patterns indicated that the aged auditory cortex demonstrated
      a homogenous, distributed coding strategy, compared to the selective, sparse
      coding strategy observed in the young monkeys. Degraded temporal fidelity and
      highly-responsive, broadly-tuned cortical responses could underlie how aged
      humans have difficulties to resolve and track dynamic sounds leading to speech
      processing deficits.

PMID- 29040404
TI  - Variables That Impact Medical Malpractice Claims Involving Plastic Surgeons in
      the United States.
AB  - Background: Medical malpractice lawsuits contribute directly and indirectly to
      the cost of healthcare in the United States. Reducing medical malpractice claims
      represents an often unrecognized opportunity for improving both the quality and
      affordability of healthcare. Objectives: The aim of this study was to better
      understand variables of the informed consent process that may contribute to
      reducing malpractice claims in plastic surgery. Methods: A prospective multiple
      choice questionnaire was distributed via email to all of the 1694 members of the
      American Society for Aesthetic Plastic Surgery (ASAPS) to evaluate attitudes and
      practices of informed consent in relation to medical malpractice. Results: A
      total of 129 questionnaires obtained from plastic surgeons were eligible for
      analysis (response rate 7.6%). Respondents who provided procedure-specific
      brochures to their patients were significantly less likely to be sued for medical
      malpractice (P = 0.004) than those who did not. Plastic surgeons that
      participated in malpractice carrier-required courses on avoiding medical
      malpractice litigation had a similarly significantly reduced likelihood of
      lawsuits. (P = 0.04). Conclusions: Variables that may reduce malpractice claims,
      and thereby both improve the quality and affordability of healthcare, include:
      (1) the use of procedure-specific patient education brochures; and (2) physician
      participation in malpractice insurance carrier-required courses. These findings
      should be of interest to physicians, hospitals, and insurance companies.

PMID- 29040405
TI  - The Balcony Technique of Breast Augmentation and Inverted-T Mastopexy With an
      Inferior Dermoglandular Flap.
AB  - Background: Optimal breast augmentation-mastopexy involves a reliable technique,
      fast recovery, minimal complications, and aesthetic results that are excellent
      and enduring. Objectives: The authors sought to determine whether the balcony
      technique of augmentation-mastopexy was safe and yielded satisfactory long-term
      outcomes in patients with breast ptosis and hypoplasia. Methods: The authors
      conducted a retrospective review of 207 patients who underwent subglandular
      augmentation and inverted-T mastopexy with a customized Wise keyhole resection
      pattern and an inferior flap. Patient satisfaction was assessed anonymously on a
      visual analog scale via a questionnaire administered 4 years postoperatively.
      Results: A total of 182 women received follow-up for 48 months and were included
      in statistical analyses. High levels of satisfaction were determined using
      Fischer exact test for breast shape, size, and symmetry, but not for other items,
      such as scar appearance, body perception, or self-esteem. The most common
      complications were Baker II capsular contracture and wound dehiscence. No patient
      experienced nipple loss or skin flap necrosis. Conclusions: The results of this
      long-term analysis demonstrate that the balcony technique of augmentation
      mastopexy is suitable for patients with breast ptosis and hypoplasia. Level of
      Evidence: 4.

PMID- 29040406
TI  - MATAM: reconstruction of phylogenetic marker genes from short sequencing reads in
      metagenomes.
AB  - Motivation: Advances in the sequencing of uncultured environmental samples,
      dubbed metagenomics, raise a growing need for accurate taxonomic assignment.
      Accurate identification of organisms present within a community is essential to
      understanding even the most elementary ecosystems. However, current high
      throughput sequencing technologies generate short reads which partially cover
      full-length marker genes and this poses difficult bioinformatic challenges for
      taxonomy identification at high resolution. Results: We designed MATAM, a
      software dedicated to the fast and accurate targeted assembly of short reads
      sequenced from a genomic marker of interest. The method implements a stepwise
      process based on construction and analysis of a read overlap graph. It is applied
      to the assembly of 16S rRNA markers and is validated on simulated, synthetic and
      genuine metagenomes. We show that MATAM outperforms other available methods in
      terms of low error rates and recovered fractions and is suitable to provide
      improved assemblies for precise taxonomic assignments. Availability and
      implementation: https://github.com/bonsai-team/matam. Contact:
      pierre.pericard@gmail.com or helene.touzet@univ-lille1.fr. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29040408
TI  - Partial anomalous left pulmonary artery.

PMID- 29040409
TI  - Towards dynamic genome-scale models.
AB  - The analysis of the dynamic behaviour of genome-scale models of metabolism (GEMs)
      currently presents considerable challenges because of the difficulties of
      simulating such large and complex networks. Bacterial GEMs can comprise about
      5000 reactions and metabolites, and encode a huge variety of growth conditions;
      such models cannot be used without sophisticated tool support. This article is
      intended to aid modellers, both specialist and non-specialist in computerized
      methods, to identify and apply a suitable combination of tools for the dynamic
      behaviour analysis of large-scale metabolic designs. We describe a methodology
      and related workflow based on publicly available tools to profile and analyse
      whole-genome-scale biochemical models. We use an efficient approximative
      stochastic simulation method to overcome problems associated with the dynamic
      simulation of GEMs. In addition, we apply simulative model checking using
      temporal logic property libraries, clustering and data analysis, over time series
      of reaction rates and metabolite concentrations. We extend this to consider the
      evolution of reaction-oriented properties of subnets over time, including dead
      subnets and functional subsystems. This enables the generation of abstract views
      of the behaviour of these models, which can be large-up to whole genome in size
      and therefore impractical to analyse informally by eye. We demonstrate our
      methodology by applying it to a reduced model of the whole-genome metabolism of
      Escherichia coli K-12 under different growth conditions. The overall context of
      our work is in the area of model-based design methods for metabolic engineering
      and synthetic biology.

PMID- 29040410
TI  - RORalpha Coordinates Thalamic and Cortical Maturation to Instruct Barrel Cortex
      Development.
AB  - The retinoic acid-related orphan receptor alpha (RORalpha) is well-known for its
      role in cerebellar development and maturation as revealed in staggerer mice.
      However, its potential involvement in the development of other brain regions has
      hardly been assessed. Here, we describe a new role of RORalpha in the development
      of primary somatosensory maps. Staggerer mice showed a complete disruption of
      barrels in the somatosensory cortex and of barreloids in the thalamus. This
      phenotype results from a severe reduction of thalamocortical axon (TCA) branching
      and a defective maturation of layer IV cortical neurons during postnatal
      development. Conditional deletion of RORalpha was conducted in the thalamus or
      the cortex to determine the specific contribution of RORalpha in each of these
      structures to these phenotypes. This showed that RORalpha is cell-autonomously
      required in the thalamus for the organization of TCAs into periphery-related
      clusters and in the somatosensory cortex for the dendritic maturation of layer IV
      neurons. Microarray analyses revealed that Sema7a, Neph, and Adcy8 are RORalpha
      regulated genes that could be implicated in TCA and cortical maturation. Overall,
      our study outlines a new role of RORalpha for the coordinated maturation of the
      somatosensory thalamus and cortex during the assembly of columnar barrel
      structures.

PMID- 29040407
TI  - Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of
      Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes
      Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice.
AB  - Abnormal sensory responses associated with Fragile X Syndrome (FXS) and autism
      spectrum disorders include hypersensitivity and impaired habituation to repeated
      stimuli. Similar sensory deficits are also observed in adult Fmr1 knock-out (KO)
      mice and are reversed by genetic deletion of Matrix Metalloproteinase-9 (MMP-9)
      through yet unknown mechanisms. Here we present new evidence that impaired
      development of parvalbumin (PV)-expressing inhibitory interneurons may underlie
      hyper-responsiveness in auditory cortex of Fmr1 KO mice via MMP-9-dependent
      regulation of perineuronal nets (PNNs). First, we found that PV cell development
      and PNN formation around GABAergic interneurons were impaired in developing
      auditory cortex of Fmr1 KO mice. Second, MMP-9 levels were elevated in P12-P18
      auditory cortex of Fmr1 KO mice and genetic reduction of MMP-9 to WT levels
      restored the formation of PNNs around PV cells. Third, in vivo single-unit
      recordings from auditory cortex neurons showed enhanced spontaneous and sound
      driven responses in developing Fmr1 KO mice, which were normalized following
      genetic reduction of MMP-9. These findings indicate that elevated MMP-9 levels
      contribute to the development of sensory hypersensitivity by influencing
      formation of PNNs around PV interneurons suggesting MMP-9 as a new therapeutic
      target to reduce sensory deficits in FXS and potentially other autism spectrum
      disorders.

PMID- 29040411
TI  - HANDOC: A Handy Score to Determine the Need for Echocardiography in Non-beta
      Hemolytic Streptococcal Bacteremia.
AB  - Background: Non-beta-hemolytic streptococci (NBHS) can cause infective
      endocarditis (IE). Echocardiography is used to diagnose IE, but it is not known
      which patients with NBHS bacteremia should undergo echocardiography. Method:
      Medical records of patients with NBHS bacteremia in southern Sweden from 2012 to
      2014 were studied retrospectively. The patients were divided into 2 cohorts. In
      the first, correlations between the reported data and IE were studied. These
      variables were used to construct the HANDOC score, which was then validated in
      the second cohort. Results: Three hundred thirty-nine patients with NBHS
      bacteremia were included in the first cohort, of whom 26 fulfilled the criteria
      for IE. Several factors differed significantly between the patients with IE and
      those without. Among these variables, the presence of Heart murmur or valve
      disease; Aetiology with the groups of Streptococcus mutans, Streptococcus bovis,
      Streptococcus sanguinis, or Streptococcus anginosus; Number of positive blood
      cultures >=2; Duration of symptoms of 7 days or more; Only 1 species growing in
      blood cultures; and Community-acquired infection were chosen to form the HANDOC
      score. With a cutoff between 2 and 3 points, HANDOC had a sensitivity of 100% and
      specificity of 73% in the first cohort. When tested in the validation cohort (n =
      399), the sensitivity was 100% and the specificity 76%. Conclusions: HANDOC can
      be used in to identify patients with NBHS bacteremia who have a risk of IE so low
      that echocardiography can be omitted; therefore, its implementation might reduce
      the use of echocardiography.

PMID- 29040413
TI  - Bilateral cavitary multidrug- or extensively drug-resistant tuberculosis: role of
      surgery.
AB  - OBJECTIVES: Cavitary disease and bilateral lesions are among the risk factors for
      poor outcome of pulmonary tuberculosis (TB). Our aim was to explore the value and
      limits of surgery in patients with advanced TB. METHODS: A retrospective study of
      57 consecutive patients who underwent thoracic surgery for culture-positive
      bilateral cavitary pulmonary TB was performed. Forty-four (77.2%) patients were
      men and 13 (22.8%) patients were women; their ages were in the range of 18-61
      years. Twenty-two (38.6%) patients had multidrug-resistant (MDR) TB and 35
      (61.4%) patients had extensively drug-resistant (XDR) TB confirmed with cultures.
      On admission, 49 (86.0%) patients had sputum smear microscopy positive for acid
      fast bacilli. The main indication for surgery was treatment failure manifested as
      contagious persisting cavities despite best available therapy. The surgical
      procedures included combinations of pulmonary resections of different levels,
      selective thoracoplasties and/or endobronchial valve treatment. The operations
      were performed consecutively, starting with the most affected side. TB therapy
      preceded the operation for a minimum of 6 months and was continued after the
      operation on the basis of the patient's susceptibility to drugs for Mycobacterium
      tuberculosis. RESULTS: We performed 121 operations: 42 in 22 patients with MDR TB
      (1.9 operations per patient) and 79 procedures in 35 patients with XDR TB (2.3
      operations per patient). No deaths occurred in the 1st year. Two late deaths
      followed, 1 unrelated to and 1 due to TB progression. Ten major complications (1
      complication per patient) developed: main bronchus stump fistula (n = 4),
      prolonged air leak (n = 3), respiratory failure (n = 2) and wound seroma (n = 1).
      At the 1-month follow-up visit, sputum smear conversion was observed in 11
      (68.8%) patients with MDR and in 15 (45.5%) patients with XDR TB. At the late (20
      36 months) follow-up visit, culture negativity was achieved in 21 (95.5%)
      patients with MDR TB and in 23 (65.7%) patients with XDR TB (P = 0.015).
      CONCLUSIONS: Thoracic surgery may significantly improve patients' outcomes and
      even result in a cure in a good portion of patients with bilateral cavitary MDR
      and XDR TB and should be considered as the essential element of multimodality
      treatment for MDR and XDR TB, even in patients with bilateral cavitary disease
      and borderline respiratory reserves.

PMID- 29040412
TI  - Random Recurrent Networks Near Criticality Capture the Broadband Power
      Distribution of Human ECoG Dynamics.
AB  - Brain electric field potentials are dominated by an arrhythmic broadband signal,
      but the underlying mechanism is poorly understood. Here we propose that broadband
      power spectra characterize recurrent neural networks of nodes (neurons or
      clusters of neurons), endowed with an effective balance between excitation and
      inhibition tuned to keep the network on the edge of dynamical instability. These
      networks show a fast mode reflecting local dynamics and a slow mode emerging from
      distributed recurrent connections. Together, the 2 modes produce power spectra
      similar to those observed in human intracranial EEG (i.e., electrocorticography,
      ECoG) recordings. Moreover, such networks convert spatial input correlations
      across nodes into temporal autocorrelation of network activity. Consequently,
      increased independence between nodes reduces low-frequency power, which may
      explain changes observed during behavioral tasks. Lastly, varying network
      coupling causes activity changes that resemble those observed in human ECoG
      across different arousal states. The model links macroscopic features of
      empirical ECoG power to a parsimonious underlying network structure, and suggests
      mechanisms for changes observed across behavioral and arousal states. This work
      provides a computational framework to generate and test hypotheses about cellular
      and network mechanisms underlying whole brain electrical dynamics, their
      variations across states, and potential alterations in brain diseases.

PMID- 29040414
TI  - Luma is not essential for murine cardiac development and function.
AB  - Aims: Luma is a recently discovered, evolutionarily conserved protein expressed
      in mammalian heart, which is associated with the LInker of Nucleoskeleton and
      Cytoskeleton (LINC) complex. The LINC complex structurally integrates the nucleus
      and the cytoplasm and plays a critical role in mechanotransduction across the
      nuclear envelope. Mutations in several LINC components in both humans and mice
      result in various cardiomyopathies, implying they play essential, non-redundant
      roles. A single amino acid substitution of serine 358 to leucine (S358L) in Luma
      is the unequivocal cause of a distinct form of arrhythmogenic cardiomyopathy.
      However, the role of Luma in heart has remained obscure. In addition, it also
      remains to be determined how the S358L mutation in Luma leads to cardiomyopathy.
      Methods and results: To determine the role of Luma in the heart, we first
      determined the expression pattern of Luma in mouse heart. Luma was sporadically
      expressed in cardiomyocytes throughout the heart, but was highly and uniformly
      expressed in cardiac fibroblasts and vascular smooth muscle cells. We also
      generated germline null Luma mice and discovered that germline null mutants were
      viable and exhibited normal cardiac function. Luma null mice also responded
      normally to pressure overload induced by transverse aortic constriction. In
      addition, localization and expression of other LINC complex components in both
      cardiac myocytes and fibroblasts was unaffected by global loss of Luma.
      Furthermore, we also generated and characterized Luma S358L knock-in mice, which
      displayed normal cardiac function and morphology. Conclusion: Our data suggest
      that Luma is dispensable for murine cardiac development and function and that the
      Luma S358L mutation alone may not cause cardiomyopathy in mice.

PMID- 29040415
TI  - Reply to Lee and Howden.

PMID- 29040417
TI  - Neonatal immune activation depletes the ovarian follicle reserve and alters
      ovarian acute inflammatory mediators in neonatal rats.
AB  - Normal ovarian development is crucial for female reproductive success and
      longevity. Interruptions to the delicate process of initial folliculogenesis may
      lead to ovarian dysfunction. We have previously demonstrated that an early life
      immune challenge in the rat, induced by administration of lipopolysaccharide
      (LPS) on postnatal day (PND) 3 and 5, depletes ovarian follicle reserve long
      term. Here, we hypothesized that this neonatal immune challenge leads to an
      increase in peripheral and ovarian inflammatory signaling, contributing to an
      acute depletion of ovarian follicles. Morphological analysis of neonatal ovaries
      indicated that LPS administration significantly depleted PND 5 primordial
      follicle populations and accelerated follicle maturation. LPS exposure
      upregulated circulating interleukin 6, tumor necrosis factor alpha (TNFa), and C
      reactive protein on PND 5, and upregulated ovarian mRNA expression of Tnfa,
      mitogen-activated protein kinase 8 (Mapk8/Jnk1), and growth differentiation
      factor 9 (Gdf9) (P < 0.05). Mass spectrometry and cell signaling pathway analysis
      indicated upregulation of cellular pathways associated with acute phase
      signaling, and cellular survival and assembly. Apoptosis assessed by terminal
      deoxynucleotidyl transferase dUTP nick end labeling indicated significantly
      increased positive staining in the ovaries of LPS-treated neonates. These
      findings suggest that increased proinflammatory signaling within the neonatal
      ovary may be responsible for the LPS-induced depletion of the primordial follicle
      pool. These findings also have implications for female reproductive health, as
      the ovarian reserve is a major determinate of female reproductive longevity.

PMID- 29040416
TI  - Fractionating the Neurocognitive Mechanisms Underlying Working Memory:
      Independent Effects of Dopamine and Parkinson's Disease.
AB  - Deficits in working memory (WM) in Parkinson's disease (PD) are often considered
      to be secondary to dopaminergic depletion. However, the neurocognitive mechanisms
      by which dopamine causes these deficits remain highly contested, and PD is now
      also known to be associated with nondopaminergic pathology. Here, we examined how
      PD and dopaminergic medication modulate three components of WM: maintenance over
      time, updating contents with new information and making memories distracter
      resistant. Compared with controls, patients were disproportionately impaired when
      retaining information for longer durations. By applying a probabilistic model, we
      were able to reveal that the source of this error was selectively due to
      precision of memory representations degrading over time. By contrast,
      replenishing dopamine levels in PD improved executive control over both the
      ability to ignore and update, but did not affect maintenance of information
      across time. This was due to a decrease in guess responses, consistent with the
      view that dopamine serves to prevent WM representations being corrupted by
      irrelevant information, but has no impact on information decay. Cumulatively,
      these results reveal a dissociation in the neural mechanisms underlying poor WM:
      whereas dopamine reduces interference, nondopaminergic systems in PD appear to
      modulate processes that prevent information decaying more quickly over time.

PMID- 29040418
TI  - Translational medicine in the Age of Big Data.
AB  - The ability to collect, store and analyze massive amounts of molecular and
      clinical data is fundamentally transforming the scientific method and its
      application in translational medicine. Collecting observations has always been a
      prerequisite for discovery, and great leaps in scientific understanding are
      accompanied by an expansion of this ability. Particle physics, astronomy and
      climate science, for example, have all greatly benefited from the development of
      new technologies enabling the collection of larger and more diverse data. Unlike
      medicine, however, each of these fields also has a mature theoretical framework
      on which new data can be evaluated and incorporated-to say it another way, there
      are no 'first principals' from which a healthy human could be analytically
      derived. The worry, and it is a valid concern, is that, without a strong
      theoretical underpinning, the inundation of data will cause medical research to
      devolve into a haphazard enterprise without discipline or rigor. The Age of Big
      Data harbors tremendous opportunity for biomedical advances, but will also be
      treacherous and demanding on future scientists.

PMID- 29040420
TI  - The Importance of Photographic Standardization in Evaluating Microfocused
      Ultrasound Facial Skin Treatments.

PMID- 29040421
TI  - Effect of Use of Platelet-Rich Plasma (PRP) in Skin with Intrinsic Aging Process.
AB  - Background: In previous papers, we demonstrated that the treatment of human
      photoaged skin with stromal-vascular fraction-enriched fat or expanded adipose
      derived stem cells showed a decrease of elastosis and the appearance of new
      oxytalan elastic fibers in dermis and an increase in the vascular network. The
      utilization of fat plus platelet-rich plasma (PRP) led to an increase in the
      vascular permeability and reactivity of the nervous component. Objectives: The
      purpose of this study was to analyze the histologic and ultrastructural changes
      of human skin after the injection of only PRP in the retroauricular area that was
      not exposed to sun and did not present the photoaging process, in comparison with
      our previous results. Methods: This study was performed in 13 patients who were
      candidates for facelift and whose ages ranged between 45 and 65 years. The PRP
      injection was performed in the mastoidea area. Fragments of skin were removed
      before and 3 months after treatment and analyzed by optical and electron
      microscopy. Results: After the injection of PRP, we observed an increase of
      reticular dermis thickness because of the deposition of elastic fibers and
      collagen, with a fibrotic aspect. A modified pattern of adipose tissue was also
      found at the dermohypodermal junction. Significative regenerative aspects were
      not found at histologic and ultrastructural analysis. The presence of foci of
      moderate inflammation and microangiopathy were observed. Conclusions: Treatment
      with PRP increased reticular dermis thickness with a fibrotic aspect. In the long
      term, the presence of inflammation and microangiopathy caused by PRP injection
      could lead to trophic alteration of the skin and the precocious aging process.
      Level of Evidence 4: 

PMID- 29040419
TI  - High Rates of Human Fecal Carriage of mcr-1-Positive Multidrug-Resistant
      Enterobacteriaceae Emerge in China in Association With Successful Plasmid
      Families.
AB  - Background: mcr-1-mediated colistin resistance in Enterobacteriaceae is
      concerning, as colistin is used in treating multidrug-resistant
      Enterobacteriaceae infections. We identified trends in human fecal mcr-1
      positivity rates and colonization with mcr-1-positive, third-generation
      cephalosporin-resistant (3GC-R) Enterobacteriaceae in Guangzhou, China, and
      investigated the genetic contexts of mcr-1 in mcr-1-positive 3GC-R strains.
      Methods: Fecal samples were collected from in-/out-patients submitting specimens
      to 3 hospitals (2011-2016). mcr-1 carriage trends were assessed using iterative
      sequential regression. A subset of mcr-1-positive isolates was sequenced (whole
      genome sequencing [WGS], Illumina), and genetic contexts (flanking regions,
      plasmids) of mcr-1 were characterized. Results: Of 8022 fecal samples collected,
      497 (6.2%) were mcr-1 positive, and 182 (2.3%) harbored mcr-1-positive 3GC-R
      Enterobacteriaceae. We observed marked increases in mcr-1 (0% [April 2011] to 31%
      [March 2016]) and more recent (since January 2014; 0% [April 2011] to 15% [March
      2016]) increases in human colonization with mcr-1-positive 3GC-R
      Enterobacteriaceae (P < .001). mcr-1-positive 3GC-R isolates were commonly
      multidrug resistant. WGS of mcr-1-positive 3GC-R isolates (70 Escherichia coli, 3
      Klebsiella pneumoniae) demonstrated bacterial strain diversity; mcr-1 in
      association with common plasmid backbones (IncI, IncHI2/HI2A, IncX4) and
      sometimes in multiple plasmids; frequent mcr-1 chromosomal integration; and high
      mobility of the mcr-1-associated insertion sequence ISApl1. Sequence data were
      consistent with plasmid spread among animal/human reservoirs. Conclusions: The
      high prevalence of mcr-1 in multidrug-resistant E. coli colonizing humans is a
      clinical threat; diverse genetic mechanisms (strains/plasmids/insertion
      sequences) have contributed to the dissemination of mcr-1, and will facilitate
      its persistence.

PMID- 29040422
TI  - Pharmacogenetics: a general review on progress to date.
AB  - Background: Pharmacogenetics is not a new subject area but its relevance to drug
      prescribing has become clearer in recent years due to developments in gene
      cloning and DNA genotyping and sequencing. Sources of data: There is a very
      extensive published literature concerned with a variety of different genes and
      drugs. Areas of agreement: There is general agreement that pharmacogenetic
      testing is essential for the safe use of drugs such as the thiopurines and
      abacavir. Areas of controversy: Whether pharmacogenetic testing should be applied
      more widely including to the prescription of certain drugs such as warfarin and
      clopidogrel where the overall benefit is less clear remains controversial.
      Growing points: Personal genotype information is increasingly being made
      available directly to the consumer. This is likely to increase demand for
      personalized prescription and mean that prescribers need to take pharmacogenetic
      information into account. Projects such as 100 000 genomes are providing complete
      genome sequences that can form part of a patient medical record. This information
      will be of great value in personalized prescribing. Areas timely for developing
      research: Development of new drugs targeting particular genetic risk factors for
      disease. These could be prescribed to those with an at risk genotype.

PMID- 29040424
TI  - Body Contouring Surgery and the Maintenance of Weight-Loss Following Roux-En-Y
      Gastric Bypass: A Retrospective Study.
AB  - Background: Bariatric surgery leads to significant weight loss with reduced
      morbidity and mortality. However, excess skin as a consequence of weight loss
      represents a major problem, impacting upon patient's functionality with potential
      negative effects on weight loss. Objectives: We evaluated the effect of body
      contouring surgery on weight-loss maintenance following bariatric surgery.
      Methods: We undertook a retrospective analysis of patients undergoing Roux-en-Y
      gastric bypass (RYGB) +/- body-contouring surgery (BC). The control group (n =
      61) received RYGB, the test group (n = 30) received RYGB+BC 12 to 18 months after
      bariatric surgery. Each RYGB+BC patient was matched to two control patients for
      age, sex, glycaemic status, and weight on day of surgery. Per cent weight loss
      (%WL) was calculated at 3, 6, 12, 24, 36, 48, and 60 months post-RYGB for both
      groups. Results: The %WL was similar at 3, 6, and 12 months post-RYGB. At 24
      months, %WL was 35.6% in the RYGB+BC group and 30.0% in the RYGB group (P <
      0.05). At 36 months, the RYGB+BC group maintained their weight loss (%WL 33.0%),
      in contrast, the RYGB gained weight (%WL = 27.3%, P < 0.05). This trend continued
      (RYGB+BC vs RYGB) at 48 months (%WL 30.8% vs 27.0%) and at 60 months (%WL 32.2%
      vs 22.7%, P < 0.05). Conclusions: Our results suggest patients who undergo body
      contouring after bariatric surgery are able to lose significantly more weight and
      maintain weight loss at five years of follow up compared to those undergoing
      bariatric surgery alone.

PMID- 29040423
TI  - Therapeutic strategies utilizing SDF-1alpha in ischaemic cardiomyopathy.
AB  - Heart failure is rapidly increasing in prevalence and will redraw the global
      landscape for cardiovascular health. Alleviating and repairing cardiac injury
      associated with myocardial infarction (MI) is key to improving this burden.
      Homing signals mobilize and recruit stem cells to the ischaemic myocardium where
      they exert beneficial paracrine effects. The chemoattractant cytokine SDF-1alpha
      and its associated receptor CXCR4 are upregulated after MI and appear to be
      important in this context. Activation of CXCR4 promotes both cardiomyocyte
      survival and stem cell migration towards the infarcted myocardium. These effects
      have beneficial effects on infarct size, and left ventricular remodelling and
      function. However, the timing of endogenous SDF-1alpha release and CXCR4
      upregulation may not be optimal. Furthermore, current ELISA-based assays cannot
      distinguish between active SDF-1alpha, and SDF-1alpha inactivated by dipeptidyl
      peptidase 4 (DPP4). Current therapeutic approaches aim to recruit the SDF-1alpha
      CXCR4 pathway or prolong SDF-1alpha life-time by preventing its cleavage by DPP4.
      This review assesses the evidence supporting these approaches and proposes SDF
      1alpha as an important confounder in recent studies of DPP4 inhibitors.

PMID- 29040425
TI  - Apparent Age is a Reliable Assessment Tool in 20 Facelift Patients.
AB  - Background: Although the literature is replete with favorable facelift results,
      there are few validated facial rejuvenation outcome measures. Apparent age (AA),
      a visual estimate of age by objective observers, has been utilized in several
      studies; although attractive, AA lacks validation. Objective: The aim of this
      study is to examine the reliability of AA, highlighting the importance of the
      exclusive use of validated outcome measures in future studies. Methods: Ten
      blinded reviewers assessed pre- and postoperative photographs of 32 patients who
      underwent facelift. Each reviewer completed 3 surveys at 3-month intervals
      composed of 40 randomly ordered photos; totaling 1200 photographs assigned an AA.
      The intra-class correlation coefficient was classified as "excellent," "good,"
      "fair," or "poor." The accuracy of assigned AA, agreement within 5 years, and
      reduction in AA were also evaluated. Results: The mean difference of preoperative
      true age from assigned AA was 2.74 +/- 4.36 years. Forty-three percent of raters
      were within 5-years (+/-2.5) of the mean. Intra-rater reliability preoperatively
      and postoperatively were 0.77 (95% CI, 0.82-0.72) and 0.75 (95% CI, 0.79-0.71),
      respectively. Inter-rater reliability preoperatively was 0.98 (95% CI, 0.99
      0.96), while postoperatively was 0.95 (95% CI, 0.99-0.95). Mean AA reduction was
      5.23 +/- 2.81, with an intra-rater reliability 0.15 (95% CI, 0.03-0.34) and inter
      rater reliability 0.65 (95% CI, 0.84-0.38). Conclusion: Using current statistical
      measures and analysis, AA is an acceptable tool for pre- and postoperative facial
      evaluation when assessed by a group of 10 reviewers. Therefore, apparent age
      represents a reliable and valid objective observer assigned measure for
      evaluation of facelift outcomes.

PMID- 29040426
TI  - Commentary on: A Meta-Analysis of the Effects of Abdominoplasty Modifications on
      the Incidence of Postoperative Seroma.

PMID- 29040427
TI  - What Is the End of Life Period? Trajectories and Characterization Based on
      Primary Caregiver Reports.
AB  - Background: As the population lives longer, end of life (EOL) is emerging as a
      distinct life phase, about which there is still limited understanding.
      Characterizing this important period is vital for clarifying issues regarding
      trajectory and decline at EOL and for health service planning on an
      institutional, communal, and societal level. In this article, we aim to
      characterize the EOL period, examining the duration and number of EOL stages, as
      well as functional, attitudinal, and emotional trajectories. Methods: In this
      cross-sectional study, 70 primary caregivers of deceased persons were
      interviewed. Standardized rates of functional, attitudinal, and emotional change
      across the EOL period were calculated. Frequencies were compared using the
      McNemar statistical test. Results: EOL period was found to have a median length
      of 3.25 years, and an average of approximately three progressive stages. The
      duration of EOL stages tended to decrease as death approached. Unexpected events
      (eg new medical diagnosis/accident) served as the precipitating event for the EOL
      period for approximately half of the deceased persons, and changes in existing
      conditions (eg health status/cognitive state) were also reported to precipitate
      EOL for a similar proportion. Reports of functionality across stages found the
      steepest decline in the "physical" domain and the most moderate decline in the
      "social" domain. With each stage, positive indicators, such as "will to live,"
      showed a progressive decline, whereas negative indicators, including "suffering"
      and "dependence level," progressively increased. Conclusions: Results help
      characterize EOL trajectories and should inform care planning and decision making
      at various levels. In addition, they suggest a methodology for better
      understanding EOL.

PMID- 29040428
TI  - Understanding the Promises and Hurdles of Metagenomic Next-Generation Sequencing
      as a Diagnostic Tool for Infectious Diseases.
AB  - Agnostic metagenomic next-generation sequencing (mNGS) has emerged as a promising
      single, universal pathogen detection method for infectious disease diagnostics.
      This methodology allows for identification and genomic characterization of
      bacteria, fungi, parasites, and viruses without the need for a priori knowledge
      of a specific pathogen directly from clinical specimens. Although there are
      increasing reports of mNGS successes, several hurdles need to be addressed, such
      as differentiation of colonization from infection, extraneous sources of nucleic
      acid, method standardization, and data storage, protection, analysis, and
      interpretation. As more commercial and clinical microbiology laboratories develop
      mNGS assays, it is important for treating practitioners to understand both the
      power and limitations of this method as a diagnostic tool for infectious
      diseases.

PMID- 29040430
TI  - Transcriptomic Landscape of Treatment-Naive Ulcerative Colitis.
AB  - Background and Aims: Ulcerative colitis [UC] is a chronic inflammatory disease
      that effects the gastrointestinal tract and is considered one of the most
      prominent and common forms of inflammatory bowel disease [IBD]. This study aimed
      to define and describe the entire transcriptomic landscape in a well-stratified,
      treatment-naive UC patient population compared with control patients by using
      next-generation technology, RNA-Seq. Methods: Mucosal biopsies from treatment
      naive UC patients [n = 14], and healthy controls [n = 16] underwent RNA-Seq.
      Principal component analysis [PCA], cell deconvolution methods, and diverse
      statistical methods were applied to obtain and characterise a dataset of
      significantly differentially expressed genes [DEGs]. Results: Analyses revealed
      1480 significantly DEGs in treatment-naive UC when compared with controls. Cell
      populations of monocytes, T cells, neutrophils, B cells/ lymphoid cells, and
      myeloid cells were increased during inflammation, whereas the fraction of
      epithelial cells were reduced in UC, which is reflected by the DEGs; 79 DEGs were
      identified as IBD susceptibility genes, and 58 DEGs were expressed in a gender
      specific manner. MUC5B, REG3A, DEFA5, and IL33 might be considered as colorectal
      cancer [CRC] risk factors following UC in males. AQP9 together with CLDN2 may
      have a role regulating tissue-specific physiological properties in tight
      junctions in UC. An additional functional role for AQP9 in the synthesis and/or
      the function of mucus can be implied. Conclusions: This study reveals new
      potential players in UC pathogenesis in general, and provides evidence for a
      gender-dependent pathogenesis for UC. These results can be useful for the
      development of personalised treatment strategies for UC in the future.

PMID- 29040429
TI  - The Role of GLP-1 in the Metabolic Success of Bariatric Surgery.
AB  - Two of the most popular bariatric procedures, vertical sleeve gastrectomy (VSG)
      and Roux-en-Y gastric bypass (RYGB), are commonly considered metabolic surgeries
      because they are thought to affect metabolism in a weight loss-independent
      manner. In support of this classification, improvements in glucose homeostasis,
      insulin sensitivity, and even discontinuation of type 2 diabetes mellitus (T2DM)
      medication can occur before substantial postoperative weight loss. The mechanisms
      that underlie this effect are unknown. However, one of the common findings after
      VSG and RYGB in both animal models and humans is the sharp postprandial rise in
      several gut peptides, including the incretin and satiety peptide glucagonlike
      peptide-1 (GLP-1). The increase in endogenous GLP-1 signaling has been considered
      a primary pathway leading to postsurgical weight loss and improvements in glucose
      metabolism. However, the degree to which GLP-1 and other gut peptides are
      responsible for the metabolic successes after bariatric surgery is continually
      debated. In this review we discuss the mechanisms underlying the increase in GLP
      1 and its potential role in the metabolic improvements after bariatric surgery,
      including remission of T2DM. Understanding the role of changes in gut peptides,
      or lack thereof, will be crucial in understanding the critical factors necessary
      for the metabolic success of bariatric surgery.

PMID- 29040431
TI  - Prevention of breast cancer-induced osteolytic bone resorption by benzyl
      isothiocyanate.
AB  - Osteolytic bone resorption is the primary cause of pain and suffering (e.g.
      pathological bone fracture) in women with metastatic breast cancer. The current
      standard of care for patients with bone metastasis for reducing the incidence of
      skeletal complications includes bisphosphonates and a humanized antibody
      (denosumab). However, a subset of patients on these therapies still develops new
      bone metastasis or experiences adverse effects. Moreover, some bisphosphonates
      have poor oral bioavailability. Therefore, orally-bioavailable and non-toxic
      inhibitors of breast cancer-induced osteolytic bone resorption are still
      clinically desirable. We have shown previously that benzyl isothiocyanate (BITC)
      decreases the incidence of breast cancer in a transgenic mouse model without any
      side effects. The present study provides in vivo evidence for inhibition of
      breast cancer-induced osteolytic bone resorption by BITC. Plasma achievable doses
      of BITC (0.5 and 1 MUM) inhibited in vitro osteoclast differentiation induced by
      co-culture of osteoclast precursor cells (RAW264.7) and breast cancer cells
      representative of different subtypes. This effect was accompanied by
      downregulation of key mediators of osteoclast differentiation, including receptor
      activator of nuclear factor-kappaB ligand and runt-related transcription factor 2
      (RUNX2), in BITC-treated breast cancer cells. Doxycycline-inducible knockdown of
      RUNX2 augmented BITC-mediated inhibition of osteoclast differentiation. Oral
      administration of 10 mg BITC/kg body weight, 5 times per week, inhibited MDA-MB
      231-induced skeletal metastasis multiplicity by ~81% when compared with control
      (P = 0.04). The present study indicates that BITC has the ability to inhibit
      breast cancer-induced osteolytic bone resorption in vivo.

PMID- 29040432
TI  - Machine learning accelerates MD-based binding pose prediction between ligands and
      proteins.
AB  - Motivation: Fast and accurate prediction of protein-ligand binding structures is
      indispensable for structure-based drug design and accurate estimation of binding
      free energy of drug candidate molecules in drug discovery. Recently, accurate
      pose prediction methods based on short Molecular Dynamics (MD) simulations, such
      as MM-PBSA and MM-GBSA, among generated docking poses have been used. Since
      molecular structures obtained from MD simulation depend on the initial condition,
      taking the average over different initial conditions leads to better accuracy.
      Prediction accuracy of protein-ligand binding poses can be improved with multiple
      runs at different initial velocity. Results: This paper shows that a machine
      learning method, called Best Arm Identification, can optimally control the number
      of MD runs for each binding pose. It allows us to identify a correct binding pose
      with a minimum number of total runs. Our experiment using three proteins and
      eight inhibitors showed that the computational cost can be reduced substantially
      without sacrificing accuracy. This method can be applied for controlling all
      kinds of molecular simulations to obtain best results under restricted
      computational resources. Availability and implementation: Code and data are
      available on GitHub at https://github.com/tsudalab/bpbi. Contact:
      terayama@cbms.k.u-tokyo.ac.jp or tsuda@k.u-tokyo.ac.jp. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29040433
TI  - Low end-tidal CO2 as a real-time severity marker of intra-anaesthetic acute
      hypersensitivity reactions.
AB  - Background: Prompt diagnosis of intra-anaesthetic acute hypersensitivity
      reactions (AHR) is challenging because of the possible absence and/or difficulty
      in detecting the usual clinical signs and because of the higher prevalence of
      alternative diagnoses. Delayed epinephrine administration during AHR, because of
      incorrect/delayed diagnosis, can be associated with poor prognosis. Low end-tidal
      CO2 (etCO2) is known to be linked to low cardiac output. Yet, its clinical
      utility during suspected intra-anaesthetic AHR is not well documented. Methods:
      Clinical data from the 86 patients of the Neutrophil Activation in Systemic
      Anaphylaxis (NASA) multicentre study were analysed. Consenting patients with
      clinical signs consistent with intra-anaesthetic AHR to a neuromuscular blocking
      agent were included. Severe AHR was defined as a Grade 3-4 of the Ring and
      Messmer classification. Causes of AHR were explored following recommended
      guidelines. Results: Among the 86 patients, 50% had severe AHR and 69% had a
      confirmed/suspected IgE-mediated event. Occurrence and minimum values of arterial
      hypotension, hypocapnia and hypoxaemia increased significantly with the severity
      of AHR. Low etCO2 was the only factor able to distinguish mild [median 3.5
      (3.2;3.9) kPa] from severe AHR [median 2.4 (1.6;3.0) kPa], without overlap in
      inter-quartile range values, with an area under the receiver operator
      characteristic curve of 0.92 [95% confidence interval: 0.79-1.00]. Among the 41%
      of patients who received epinephrine, only half received it as first-line therapy
      despite international guidelines. Conclusions: An etCO2 value below 2.6 kPa (20
      mm Hg) could be useful for prompt diagnosis of severe intra-anaesthetic AHR, and
      could facilitate early treatment with titrated doses of epinephrine. Clinical
      trial registration: NCT01637220.

PMID- 29040434
TI  - Differential Processing of Isolated Object and Multi-item Pop-Out Displays in LIP
      and PFC.
AB  - Objects that are highly distinct from their surroundings appear to visually "pop
      out." This effect is present for displays in which: (1) a single cue object is
      shown on a blank background, and (2) a single cue object is highly distinct from
      surrounding objects; it is generally assumed that these 2 display types are
      processed in the same way. To directly examine this, we applied a decoding
      analysis to neural activity recorded from the lateral intraparietal (LIP) area
      and the dorsolateral prefrontal cortex (dlPFC). Our analyses showed that for the
      single-object displays, cue location information appeared earlier in LIP than in
      dlPFC. However, for the display with distractors, location information was
      substantially delayed in both brain regions, and information first appeared in
      dlPFC. Additionally, we see that pattern of neural activity is similar for both
      types of displays and across different color transformations of the stimuli,
      indicating that location information is being coded in the same way regardless of
      display type. These results lead us to hypothesize that 2 different pathways are
      involved processing these 2 types of pop-out displays.

PMID- 29040436
TI  - Academic Productivity: A Guide for Students, Residents, and Fellows.

PMID- 29040438
TI  - Geometric predictors of left ventricular outflow tract obstruction in patients
      with hypertrophic cardiomyopathy: a 3D computed tomography analysis.
AB  - Aims: To establish geometric predictors of left ventricular outflow tract
      obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) patients by use of
      cardiac computed tomography (CT). Methods and results: A total of 141 consecutive
      patients with HCM who underwent cardiac CT comprised the analytic sample. The
      degree, pattern, and extent of left ventricular (LV) hypertrophy were evaluated
      using 3D CT. Abnormality of papillary muscle (PM), mitral valve, and aorto-mitral
      angle were evaluated quantitatively. Multivariable logistic regression analysis
      and sensitivity analysis were performed to reliably identify predictors of LVOTO.
      LVOTO was present among 40 (28.4%) patients. Those with LVOTO displayed a higher
      prevalence for having a spiral pattern of LV hypertrophy (e.g. 51 vs. 16%, P <
      0.001), a longer anterior mitral leaflet (AML) length (e.g. 18.0 vs. 15.6 mm, P =
      0.007), and a longer distance from lateral PM base to LV apex (e.g. 26.4 vs. 22.0
      mm, P < 0.001), as compared with the non-LVOTO group. Multivariable logistic
      regression revealed all three variables [i.e. spiral pattern (95% confidence
      interval (CI), 3.75, 1.59-8.84); AML length (95% CI, 1.20, 1.03-1.40); the
      distance between lateral PM base and LV apex (95% CI, 1.09, 1.01-1.19)] retained
      significance after adjustment for numerous covariates. Conclusion: Spiral pattern
      of LV hypertrophy, the length of AML, and the distance between lateral PM base
      and LV apex were independent predictors of LVOTO in patients with HCM.

PMID- 29040437
TI  - Sperm Release at Spermiation Is Regulated by Changes in the Organization of Actin
      and Microtubule-Based Cytoskeletons at the Apical Ectoplasmic Specialization-A
      Study Using the Adjudin Model.
AB  - The mechanism that regulates sperm release at spermiation is unknown. Herein, we
      used an animal model wherein rats were treated with adjudin, 1-(2,4
      dichlorobenzyl)-1H-indazole-3-carbohydrazide, via oral gavage to induce premature
      release of elongating/elongated spermatids, followed by round spermatids and
      spermatocytes. Spermatid release mimicking spermiation occurred within 6 to 12
      hours following adjudin treatment and, by 96 hours, virtually all tubules were
      devoid of elongating/elongated spermatids. Using this model, we tracked the
      organization of F-actin and microtubules (MTs) by immunofluorescence microscopy,
      and the association of actin or MT regulatory proteins that either promote or
      demolish cytoskeletal integrity through changes in the organization of actin
      microfilaments or MTs by coimmunoprecipitation. Adjudin treatment induced an
      increase in the association of (1) epidermal growth factor receptor pathway
      substrate 8 (an actin barbed-end capping and bundling protein) or formin 1 (an
      actin nucleator) with actin and (2) end-binding protein 1 (an MT stabilizing
      protein) with MT shortly after adjudin exposure (at 6 hours), in an attempt to
      maintain spermatid adhesion to the Sertoli cell at the apical ectoplasmic
      specialization (ES). However, this was followed by a considerable decline of
      their steady-state protein levels, replacing with an increase in association of
      (1) actin-related protein 3 (a branched actin nucleator that converts actin
      filaments into a branched/unbundled network) with actin and (2) MT affinity
      regulating kinase 4 (an MT destabilizing protein kinase) with MTs by 12 hours
      after adjudin treatment. These latter changes thus promoted actin and MT
      disorganization, leading to apical ES disruption and the release of
      elongating/elongated spermatids, mimicking spermiation. In summary, spermiation
      is a cytoskeletal-dependent event, involving regulatory proteins that modify
      cytoskeletal organization.

PMID- 29040439
TI  - Eicosapentaenoic acid attenuates obesity-related hepatocellular carcinogenesis.
AB  - Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of obesity,
      is an emerging risk factor for hepatocellular carcinoma (HCC). Accumulating
      evidence has shown that chronic inflammation represents a plausible link between
      obesity and HCC and that the pro-inflammatory cytokine interleukin (IL)-6
      contributes to the development of obesity-related HCC. In the present study, we
      aimed to examine the therapeutic potential of the omega-3 polyunsaturated fatty
      acid, eicosapentaenoic acid (EPA), which exerts anti-inflammatory effects. The
      results showed that the development of carcinogen-induced HCC was significantly
      less in mice fed a high-fat diet (HFD) supplemented with EPA than in those fed
      HFD only, suggesting that EPA attenuates the development of obesity-related HCC.
      Although EPA did not appear to affect obesity-linked inflammation, it suppressed
      the activation of the pro-tumorigenic IL-6 effector STAT3, contributing to the
      inhibition of tumor growth. These findings suggest a clinical implication of EPA
      as a treatment for obesity-related HCC.

PMID- 29040441
TI  - Advancing precision medicine for the treatment of long-QT syndrome type 2:
      shedding light on lumacaftor.

PMID- 29040440
TI  - Trends in lifestyle among three cohorts of adults aged 55-64 years in 1992/1993,
      2002/2003 and 2012/2013.
AB  - Background: Unhealthy lifestyle factors, such as obesity, smoking, excessive
      alcohol consumption and physical inactivity, are associated with increased
      morbidity and mortality risk, even in older age. We investigated trends in
      lifestyle among three cohorts of adults aged 55-64 years from the Netherlands.
      Methods: Data from the Longitudinal Aging Study Amsterdam were used. This study
      consisted of three randomly selected samples of men and women. Lifestyle data
      were collected in 1992/1993 (cohort 1, n = 988), in 2002/2003 (cohort 2, n =
      1002) and in 2012/2013 (cohort 3, n = 1023). Trends in lifestyle across cohorts
      were tested using multivariable regression analyses. Results: Complete lifestyle
      data were available for 834 participants from cohort 1, 861 from cohort 2 and 845
      from cohort 3. Among men, but not in women, mean BMI and prevalence of obesity
      increased over time. The mean minutes per day spent being physically active
      decreased among both men and women, from 130 +/- 107 and 230 +/- 122 (1992/1993)
      to 114 +/- 100 and 192 +/- 109 (2002/2003), and 126 +/- 98 and 187 +/- 112
      (2012/2013), respectively. The percentage of men and women defined as excessive
      drinkers (>7 alcoholic consumptions per week) increased from 54.9%, 62.3% to
      65.4% (men) and 22.7%, 36.1% to 37.4% (women), in 1992/1993, 2002/2003 and
      2012/2013, respectively. The percentage of non-smoking men and women increased
      over time. Conclusion: The lifestyle of Dutch adults aged 55-64 years was less
      healthy in 2012/2013 compared with 2002/2003 and 1992/1993. Political attention
      regarding healthy ageing should target the prevention of overweight, physical
      inactivity and excessive alcohol consumption in middle-aged persons.

PMID- 29040442
TI  - Catecholamine crisis presenting as takotsubo cardiomyopathy caused by a 30-year
      old 'Benign' thoracic tumour.

PMID- 29040443
TI  - A dysbiosis index to assess microbial changes in fecal samples of dogs with
      chronic inflammatory enteropathy.
AB  - Recent studies have identified various bacterial groups that are altered in dogs
      with chronic inflammatory enteropathies (CE) compared to healthy dogs. The study
      aim was to use quantitative PCR (qPCR) assays to confirm these findings in a
      larger number of dogs, and to build a mathematical algorithm to report these
      microbiota changes as a dysbiosis index (DI). Fecal DNA from 95 healthy dogs and
      106 dogs with histologically confirmed CE was analyzed. Samples were grouped into
      a training set and a validation set. Various mathematical models and combination
      of qPCR assays were evaluated to find a model with highest discriminatory power.
      The final qPCR panel consisted of eight bacterial groups: total bacteria,
      Faecalibacterium, Turicibacter, Escherichia coli, Streptococcus, Blautia,
      Fusobacterium and Clostridium hiranonis. The qPCR-based DI was built based on the
      nearest centroid classifier, and reports the degree of dysbiosis in a single
      numerical value that measures the closeness in the l2 - norm of the test sample
      to the mean prototype of each class. A negative DI indicates normobiosis, whereas
      a positive DI indicates dysbiosis. For a threshold of 0, the DI based on the
      combined dataset achieved 74% sensitivity and 95% specificity to separate healthy
      and CE dogs.

PMID- 29040444
TI  - Reestablishment of Energy Balance in a Male Mouse Model With POMC Neuron Deletion
      of BMPR1A.
AB  - The regulation of energy balance involves complex processes in the brain,
      including coordination by hypothalamic neurons that contain pro-opiomelanocortin
      (POMC). We previously demonstrated that central bone morphogenetic protein (BMP)
      7 reduced appetite. Now we show that a type 1 BMP receptor, BMPR1A, is
      colocalized with POMC neurons and that POMC-BMPR1A-knockout (KO) mice are
      hyperphagic, revealing physiological involvement of BMP signaling in anorectic
      POMC neurons in the regulation of appetite. Surprisingly, the hyperphagic POMC
      BMPR1A-KO mice exhibited a lack of obesity, even on a 45% high-fat diet. This is
      because the brown adipose tissue (BAT) of KO animals exhibited increased
      sympathetic activation and greater thermogenic capacity owing to a
      reestablishment of energy balance, most likely stemming from a compensatory
      increase of BMPR1A in the whole hypothalamus of KO mice. Indeed, control animals
      given central BMP7 displayed increased energy expenditure and a specific increase
      in sympathetic nerve activity (SNA) in BAT. In these animals, pharmacological
      blockade of BMPR1A-SMAD signaling blunted the ability of BMP7 to increase energy
      expenditure or BAT SNA. Together, we demonstrated an important role for
      hypothalamic BMP signaling in the regulation of energy balance, including BMPR1A
      mediated appetite regulation in POMC neurons as well as hypothalamic BMP-SMAD
      regulation of the sympathetic drive to BAT for thermogenesis.

PMID- 29040445
TI  - Rationale and Design of the Effectiveness of LowEr maintenanCe dose of TicagRelor
      early After myocardial infarction (ELECTRA) pilot study.
AB  - Aims: The degree and time course of platelet inhibition using ticagrelor can vary
      during the acute phase and the following stable period after acute myocardial
      infarction (AMI). The optimal level of platelet inhibition during the various
      stages of AMI remains an open question. The aim of the current study is to
      compare the antiplatelet efficacy of two ticagrelor maintenance dose regimens (60
      mg b.i.d. vs. 90 mg b.i.d.) in stable patients following an initial strategy with
      ticagrelor 90 mg b.i.d. during the first month after AMI. Methods and results:
      The Effectiveness of LowEr maintenanCe dose of TicagRelor early After myocardial
      infarction (ELECTRA) pilot study is a phase III, single-centre, randomized, open
      label, pharmacokinetic/pharmacodynamic trial. The study population will include
      50 patients with AMI treated with percutaneous coronary intervention. At Day 30
      post-AMI, all trial participants will be randomly assigned in 1:1 ratio to
      receive either reduced (60 mg b.i.d.) or standard (90 mg b.i.d.) maintenance
      ticagrelor dose until Day 45 post-AMI. Platelet function testing in each patient
      will be performed using up to two different methods (the VASP assay and multiple
      electrode aggregometry). Pharmacokinetics of ticagrelor and its active metabolite
      (AR-C124910XX) will be assessed by liquid chromatography mass spectrometry.
      Conclusion: A de-escalation strategy with reduced dose of ticagrelor (60 mg
      b.i.d.) following an initial standard dose (90 mg b.i.d.) during the first month
      after AMI may provide equally effective platelet inhibition as compared to
      maintenance with the standard ticagrelor dose. ClinicalTrials. gov Identifier:
      NCT03251859.

PMID- 29040446
TI  - Familial Aggregation and Heritability of Loa loa Microfilaremia.
AB  - Background: For a given prevalence of Loa loa microfilaremia, the proportion of
      people with high densities varies significantly between communities. We
      hypothesized that this variation is related to the existence of familial clusters
      of hypermicrofilaremic individuals that would be the consequence of a genetic
      predisposition to present high L. loa microfilarial densities. Methods: A
      familial study was performed in 10 villages in the Okola Health District of
      Cameroon. Intrafamilial correlation coefficients and heritability estimates were
      assessed for both the presence of L. loa microfilaremia and individual
      microfilarial densities by controlling for age, sex, Mansonella perstans
      coinfection, and household effects. Results: Pedigrees were constructed for 1126
      individuals. A significant familial susceptibility to be microfilaremic for L.
      loa was found for first-degree relatives (rho = 0.08, P < .05; heritability =
      0.23). Regarding individual microfilarial densities, a significant familial
      aggregation was demonstrated (rho = 0.36 for first-degree and 0.27 for second
      degree relatives). For first-degree relatives, the highest coefficient was found
      between mothers and daughters (rho = 0.57). The overall heritability estimate for
      L. loa microfilarial density was 0.24 (P = .003). Conclusions: A significant
      genetic component governs L. loa microfilarial density. This supports the
      hypothesis that a genetic predisposition to be hypermicrofilaremic exists,
      leading to the presence of familial clusters of individuals at risk for
      postivermectin severe adverse events. This finding should be taken into account
      while developing sampling strategies (including a household-level sampling) to
      identify villages where community-directed treatment with ivermectin cannot be
      applied.

PMID- 29040447
TI  - Transient complete atrioventricular block during catheter balloon cryoablation of
      atrial fibrillation: a case report.

PMID- 29040448
TI  - Male Brown Fat-Specific Double Knockout of IGFIR/IR: Atrophy, Mitochondrial
      Fission Failure, Impaired Thermogenesis, and Obesity.
AB  - It is unknown how the lack of insulin receptor (IR)/insulinlike growth factor I
      receptor (IGFIR) in a tissue-specific manner affects brown fat development and
      mitochondrial integrity and function, as well as its effect on the redistribution
      of the adipose organ and the metabolic status. To address this important issue,
      we developed IR/IGFIR double-knockout (DKO) in a brown adipose tissue-specific
      manner. Lack of those receptors caused severe brown fat atrophy, enhanced beige
      cell clusters in inguinal fat; loss of mitochondrial mass; mitochondrial damage
      related to cristae disruption; and the loss of proteins involved in autophagosome
      formation, mitophagy, mitochondrial quality control, and dynamics and
      thermogenesis. More important, DKO mice showed an impaired thermogenesis upon
      cold exposure, based on a failure in the mitochondrial fission mechanisms and a
      much lower uncoupling protein 1 transcription rate and content. As a result, DKO
      mice under normal conditions showed an obesity susceptibility, revealed by
      increased body fat mass and insulin resistance. Upon consumption of a high-fat
      diet, DKO mice displayed frank obesity, as shown by increased body weight,
      increased adiposity, insulin resistance, hyperinsulinemia, and
      hypertriglyceridemia, all consistent with a metabolic syndrome. Collectively, our
      data suggest a cause-and-effect relationship between failure in brown fat
      thermogenesis and increased adiposity and obesity.

PMID- 29040450
TI  - Dilated cardiomyopathy complicated with visceral heterotaxy.

PMID- 29040449
TI  - Response to letter to the editor of Carcinogenesis by Pira et al., 2017.

PMID- 29040451
TI  - An omnibus test for differential distribution analysis of microbiome sequencing
      data.
AB  - Motivation: One objective of human microbiome studies is to identify
      differentially abundant microbes across biological conditions. Previous
      statistical methods focus on detecting the shift in the abundance and/or
      prevalence of the microbes and treat the dispersion (spread of the data) as a
      nuisance. These methods also assume that the dispersion is the same across
      conditions, an assumption which may not hold in presence of sample heterogeneity.
      Moreover, the widespread outliers in the microbiome sequencing data make existing
      parametric models not overly robust. Therefore, a robust and powerful method that
      allows covariate-dependent dispersion and addresses outliers is still needed for
      differential abundance analysis. Results: We introduce a novel test for
      differential distribution analysis of microbiome sequencing data by jointly
      testing the abundance, prevalence and dispersion. The test is built on a zero
      inflated negative binomial regression model and winsorized count data to account
      for zero-inflation and outliers. Using simulated data and real microbiome
      sequencing datasets, we show that our test is robust across various biological
      conditions and overall more powerful than previous methods. Availability and
      implementation: R package is available at
      https://github.com/jchen1981/MicrobiomeDDA. Contact: chen.jun2@mayo.edu or
      zhiwei@njit.edu. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 29040452
TI  - Assessment of Vegetable and Fruit Substrates as Potential Rearing Media for
      Hermetia illucens (Diptera: Stratiomyidae) Larvae.
AB  - Hermetia illucens (L.) (Diptera: Stratiomyidae) is able to consume a wide range
      of organic matter and is of particular interest for waste management. The
      nutritional value of preimaginal stages, in particular the protein content, makes
      this species a valid candidate for use as feed for other organisms. Vegetables
      and fruits are promising rearing substrates for insects produced for this purpose
      according to the EU regulation. In order to examine the effects of diets on
      insect performance and chemical composition, larvae were reared on the following
      substrates: 1) fruit (apple, pear, and orange); 2) vegetable (lettuce, green
      beans, and cabbage); and 3) mixed fruits and vegetables. High percentages of
      survival were observed on all diets, but there were differences among weights of
      larvae, pupae, and adults, with weights of larvae reared on mixed fruits and
      vegetables lower than on other diets. Pupae reared on the mixed diet were
      heaviest, and also morphometric measurements of adults were highest. Larvae
      reared on fruit diets had the highest fat content, comprising mostly saturated
      fatty acids; the highest content of essential n-3 fatty acids was found in
      vegetable reared larvae and that of n-6 in mixed reared larvae. Larvae reared on
      the mixed diet had the highest protein content. Calcium contents were high and
      moderate amounts of iron and zinc were found. H. illucens showed the capability
      to develop on vegetable and fruits diets displaying different nutrient profiles
      and biological performances. The best-performing rearing strategy should vary in
      relation to the final use of H. illucens.

PMID- 29040453
TI  - Detection of sputum by interpreting the time-frequency distribution of
      respiratory sound signal using image processing techniques.
AB  - Motivation: Sputum in the trachea is hard to expectorate and detect directly for
      the patients who are unconscious, especially those in Intensive Care Unit.
      Medical staff should always check the condition of sputum in the trachea. This is
      time-consuming and the necessary skills are difficult to acquire. Currently,
      there are few automatic approaches to serve as alternatives to this manual
      approach. Results: We develop an automatic approach to diagnose the condition of
      the sputum. Our approach utilizes a system involving a medical device and
      quantitative analytic methods. In this approach, the time-frequency distribution
      of respiratory sound signals, determined from the spectrum, is treated as an
      image. The sputum detection is performed by interpreting the patterns in the
      image through the procedure of preprocessing and feature extraction. In this
      study, 272 respiratory sound samples (145 sputum sound and 127 non-sputum sound
      samples) are collected from 12 patients. We apply the method of leave-one out
      cross-validation to the 12 patients to assess the performance of our approach.
      That is, out of the 12 patients, 11 are randomly selected and their sound samples
      are used to predict the sound samples in the remaining one patient. The results
      show that our automatic approach can classify the sputum condition at an accuracy
      rate of 83.5%. Availability and implementation: The matlab codes and examples of
      datasets explored in this work are available at Bioinformatics online. Contact:
      yesoyou@gmail.com or douglaszhang@umac.mo. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29040454
TI  - To fly as a pilot after cardiac surgery.
AB  - Aircrew are responsible for safe and reliable aircraft operations. Cardiovascular
      disease accounts for 50% of all pilot licences declined or withdrawn for medical
      reasons in Western Europe and is the most common cases of sudden incapacitation
      in flight. Aircrew retirement age is increasing (up to age 65) in a growing
      number of airlines and the burden of subclinical, but potentially significant,
      coronary atherosclerosis is unknown in qualified pilots above age 40. Safety
      considerations are paramount in aviation medicine, and the most dreaded
      cardiovascular complications are thromboembolic events and rhythm disturbances
      due to their potential for sudden incapacitation. In aviation, the current
      consensus risk threshold for an acceptable level of controlled risk of acute
      incapacitation is 1% (for dual pilot commercial operations), a percentage
      calculated using engineering principles to ensure the incidence of a fatal air
      accident is no greater than 1 per 107 h of flying. This is known as the '1%
      safety rule'. To fly as a pilot after cardiac surgery is possible; however,
      special attention to perioperative planning is mandatory. Choice of procedure is
      crucial for license renewal. Licensing restrictions are likely to apply and the
      postoperative follow-up requires a tight scheduling. The cardiac surgeon should
      always liaise and communicate with the pilot's aviation medicine examiner prior
      to and following cardiac surgery.

PMID- 29040455
TI  - Influence of deep neuromuscular block on the surgeons assessment of surgical
      conditions during laparotomy: a randomized controlled double blinded trial with
      rocuronium and sugammadex.

PMID- 29040456
TI  - Response to letter to the editor from F. Jacques et al.

PMID- 29040457
TI  - Treatment of Chronic Q Fever: Clinical Efficacy and Toxicity of Antibiotic
      Regimens.
AB  - Background: Evidence on the effectiveness of first-line treatment for chronic Q
      fever, tetracyclines (TET) plus hydroxychloroquine (HCQ), and potential
      alternatives is scarce. Methods: We performed a retrospective, observational
      cohort study to assess efficacy of treatment with TET plus quinolones (QNL), TET
      plus QNL plus HCQ, QNL monotherapy, or TET monotherapy compared to TET plus HCQ
      in chronic Q fever patients. We used a time-dependent Cox proportional hazards
      model to assess our primary (all-cause mortality) and secondary outcomes (first
      disease-related event and therapy failure). Results: We assessed 322 chronic Q
      fever patients; 276 (86%) received antibiotics. Compared to TET plus HCQ (n =
      254; 92%), treatment with TET plus QNL (n = 49; 17%), TET plus QNL plus HCQ (n =
      29, 10%), QNL monotherapy (n = 93; 34%), or TET monotherapy (n = 54; 20%) were
      not associated with primary or secondary outcomes. QNL and TET monotherapies were
      frequently discontinued due to insufficient clinical response (n = 27, 29% and n
      = 32, 59%). TET plus HCQ, TET plus QNL, and TET plus QNL plus HCQ were most
      frequently discontinued due to side effects (n = 110, 43%; n = 13, 27%; and n =
      12, 41%). Conclusions: Treatment of chronic Q fever with TET plus QNL appears to
      be a safe alternative for TET plus HCQ, for example, if TET plus HCQ cannot be
      tolerated due to side effects. Treatment with TET plus QNL plus HCQ was not
      superior to treatment with TET plus HCQ, although this may be caused by
      confounding by indication. Treatment with TET or QNL monotherapy should be
      avoided; switches due to subjective, insufficient clinical response were
      frequently observed.

PMID- 29040458
TI  - Orchestration of the mammalian host cell glucose transporter proteins-1 and 3 by
      Chlamydia contributes to intracellular growth and infectivity.
AB  - Chlamydia are gram-negative obligate intracellular bacteria that replicate within
      a discrete cellular vacuole, called an inclusion. Although it is known that
      Chlamydia require essential nutrients from host cells to support their
      intracellular growth, the molecular mechanisms for acquiring these macromolecules
      remain uncharacterized. In the present study, it was found that the expression of
      mammalian cell glucose transporter proteins 1 (GLUT1) and glucose transporter
      proteins 3 (GLUT3) were up-regulated during chlamydial infection. Up-regulation
      was dependent on bacterial protein synthesis and Chlamydia-induced MAPK kinase
      activation. GLUT1, but not GLUT3, was observed in close proximity to the
      inclusion membrane throughout the chlamydial developmental cycle. The proximity
      of GLUT1 to the inclusion was dependent on a brefeldin A-sensitive pathway.
      Knockdown of GLUT1 and GLUT3 with specific siRNA significantly impaired
      chlamydial development and infectivity. It was discovered that the GLUT1 protein
      was stabilized during infection by inhibition of host-dependent ubiquitination of
      GLUT1, and this effect was associated with the chlamydial deubiquitinase effector
      protein CT868. This report demonstrates that Chlamydia exploits host-derived
      transporter proteins altering their expression, turnover and localization.
      Consequently, host cell transporter proteins are manipulated during infection as
      a transport system to fulfill the carbon source requirements for Chlamydia.

PMID- 29040459
TI  - UC2 search: using unique connectivity of uncharged compounds for metabolite
      annotation by database searching in mass spectrometry-based metabolomics.
AB  - Summary: For metabolite annotation in metabolomics, variations in the registered
      states of compounds (charged molecules and multiple components, such as salts)
      and their redundancy among compound databases could be the cause of
      misannotations and hamper immediate recognition of the uniqueness of metabolites
      while searching by mass values measured using mass spectrometry. We developed a
      search system named UC2 (Unique Connectivity of Uncharged Compounds), where
      compounds are tentatively neutralized into uncharged states and stored on the
      basis of their unique connectivity of atoms after removing their stereochemical
      information using the first block in the hash of the IUPAC International Chemical
      Identifier, by which false-positive hits are remarkably reduced, both charged and
      uncharged compounds are properly searched in a single query and records having a
      unique connectivity are compiled in a single search result. Availability and
      implementation: The UC2 search tool is available free of charge as a REST web
      service (http://webs2.kazusa.or.jp/mfsearcher) and a Java-based GUI tool.
      Contact: sakurai@kazusa.or.jp. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29040460
TI  - Effect of different masticatory functional demands on the 3D mandibular condyle
      morphology of growing rats using posterior bite-blocks.
AB  - Background and objectives: Apart from the primary effect of bite-blocks on tooth
      position, they may also influence the mandibular condylar growth. Our aim was to
      investigate their influence on the condylar morphology, with variable masticatory
      forces. Material and methods: Fifty-two 4-week old male rats were divided into
      hard and soft diet groups in order to create individuals with different
      masticatory muscle capacity. Two weeks later, they were equally divided into bite
      block and control groups. After a total of 6 weeks experimental time, the animals
      were sacrificed. The mandibles were scanned with high-resolution micro-CT and 3D
      analysis was performed on the condylar neck and head of the condyle. The volume
      and the length of the condylar process were measured. Statistical analysis was
      done with a one-way analysis of variance. Results: The use of bite-blocks
      decreased the length of the condylar process (P = 0.001) as well as the volume of
      the condylar neck (P = 0.001) and head (P = 0.006). The soft diet decreased the
      volume of the condylar neck (P < 0.001) and head (P < 0.001) two to three times
      more than the bite-blocks but did not affect the condylar process length. The
      interaction between the two variables was not statistically significant.
      Conclusions: Both the bite-block appliance and weak masticatory muscle function
      reduced the volume at all regions of the condylar process, although the
      functional factor had a substantially greater effect. However, only the bite
      block appliance affected the condylar process length. In the presence of both
      factors, an additive effect was found but no interaction detected.

PMID- 29040461
TI  - In vivo comparison of lipid-rich plaque on near-infrared spectroscopy with
      histopathological analysis of coronary atherectomy specimens.

PMID- 29040463
TI  - Total pericardium agenesis mistaken for arrhythmogenic right ventricular
      cardiomyopathy.

PMID- 29040462
TI  - Both cardiomyocyte and endothelial cell Nox4 mediate protection against
      hemodynamic overload-induced remodelling.
AB  - Aims: NADPH oxidase-4 (Nox4) is an important reactive oxygen species (ROS) source
      that is upregulated in the haemodynamically overloaded heart. Our previous
      studies using global Nox4 knockout (Nox4KO) mice demonstrated a protective role
      of Nox4 during chronic abdominal aortic banding, involving a paracrine
      enhancement of myocardial capillary density. However, other authors who studied
      cardiac-specific Nox4KO mice reported detrimental effects of Nox4 in response to
      transverse aortic constriction (TAC). It has been speculated that these divergent
      results are due to cell-specific actions of Nox4 (i.e. cardiomyocyte Nox4
      detrimental but endothelial Nox4 beneficial) and/or differences in the model of
      pressure overload (i.e. abdominal banding vs. TAC). This study aimed to (i)
      investigate whether the effects of Nox4 on pressure overload-induced cardiac
      remodelling vary according to the pressure overload model and (ii) compare the
      roles of cardiomyocyte vs. endothelial cell Nox4. Methods and results: Global
      Nox4KO mice subjected to TAC developed worse cardiac remodelling and contractile
      dysfunction than wild-type littermates, consistent with our previous results with
      abdominal aortic banding. Next, we generated inducible cardiomyocyte-specific
      Nox4 KO mice (Cardio-Nox4KO) and endothelial-specific Nox4 KO mice (Endo-Nox4KO)
      and studied their responses to pressure overload. Both Cardio-Nox4KO and Endo
      Nox4KO developed worse pressure overload-induced cardiac remodelling and
      dysfunction than wild-type littermates, associated with significant decrease in
      protein levels of HIF1alpha and VEGF and impairment of myocardial
      capillarization. Conclusions: Cardiomyocyte as well as endothelial cell Nox4
      contributes to protection against chronic hemodynamic overload-induced cardiac
      remodelling, at least in part through common effects on myocardial capillary
      density.

PMID- 29040464
TI  - Long-term outcome of transvenous pacemaker implantation in infants: a
      retrospective cohort study.

PMID- 29040466
TI  - Outer inflammatory protein a (OipA) of Helicobacter pylori is regulated by host
      cell contact and mediates CagA translocation and interleukin-8 response only in
      the presence of a functional cag pathogenicity island type IV secretion system.
AB  - OipA is a phase-variable virulence factor of Helicobacter pylori. Mutations in
      oipA to turn the gene phase on in a cag pathogenicity island (PAI)-negative
      strain of H. pylori (J68) or phase off in a cag PAI-positive strain (26695)
      demonstrated that phase on oipA alleles in both strains had both increased oipA
      mRNA and human gastric adenocarcinoma (AGS) cell adherence compared to isogenic
      oipA phase off mutants. An oipA phase off mutant of H. pylori 26695 demonstrated
      decreased IL-8 secretion by AGS cells and failure to translocate the cag PAI
      effector CagA. Increased attachment by OipA expressing cag PAI-negative H. pylori
      J68 failed to alter secreted IL-8 levels. Thus, OipA is necessary but not
      sufficient for the induction of IL-8; however, it is necessary for translocation
      of the oncoprotein CagA. Perhaps the nearly invariant phase on status of oipA
      alleles among cag PAI-positive H. pylori isolates relates to the role of this
      outer membrane protein in effective translocation of CagA. oipA mRNA comparisons
      between AGS cell-adherent and non-adherent H. pylori 26695 revealed significantly
      greater levels in the adherent cells. This may allow H. pylori to adapt to
      conditions of host cell contact by altering expression of this virulence factor.

PMID- 29040465
TI  - The FUT2 secretor variant p.Trp154Ter influences serum vitamin B12 concentration
      via holo-haptocorrin, but not holo-transcobalamin, and is associated with
      haptocorrin glycosylation.
AB  - Vitamin B12 deficiency is common in older individuals. Circulating vitamin B12
      concentration can be used to diagnose deficiency, but this test has substantial
      false positive and false negative rates. We conducted genome-wide association
      studies (GWAS) in which we resolved total serum vitamin B12 into the fractions
      bound to transcobalamin and haptocorrin: two carrier proteins with very different
      biological properties. We replicated reported associations between total
      circulating vitamin B12 concentrations and a common null variant in FUT2. This
      allele determines the secretor phenotype in which blood group antigens are found
      in non-blood body fluids. Vitamin B12 bound to haptocorrin (holoHC) remained
      highly associated with FUT2 rs601338 (p.Trp154Ter). Transcobalamin bound vitamin
      B12 (holoTC) was not influenced by this variant. HoloTC is the bioactive the form
      of the vitamin and is taken up by all tissues. In contrast, holoHC is only taken
      up by the liver. Using holoHC from individuals with known FUT2 genotypes, we
      demonstrated that FUT2 rs601338 genotype influences the glycosylation of
      haptocorrin. We then developed an experimental model demonstrating that holoHC is
      transported into cultured hepatic cells (HepG2) via the asialoglycoprotein
      receptor (ASGR). Our data challenge current published hypotheses on the influence
      of genetic variation on this clinically important measure and are consistent with
      a model in which FUT2 rs601338 influences holoHC by altering haptocorrin
      glycosylation, whereas B12 bound to non-glycosylated transcobalamin (i.e. holoTC)
      is not affected. Our findings explain some of the observed disparity between use
      of total B12 or holoTC as first-line clinical tests of vitamin B12 status.

PMID- 29040467
TI  - Validation of an in vitro system for studies of pathogenicity mechanisms in
      Xanthomonas campestris.
AB  - Several minimal media capable of inducing pathogenicity genes have been used to
      study plant-pathogen interactions. An in planta assay to study a closer
      interaction between the bacteria and the host was also developed and has been
      employed by our group. In order to determine whether growth medium could be
      improved to better approximate in planta conditions beyond that offered by the
      defined minimal medium XVM1, we compared the expression of 20 Xanthomonas
      campestris pv. campestris (Xcc) genes by quantitative reverse transcription -
      polymerase chain reaction (qRT-PCR) under in vivo (bacteria recovered from the
      plant) and in vitro (rich medium NYG, minimal medium XVM1 and XVM1 + leaf
      extract) growth systems. The results showed a higher expression level of the
      genes in the in planta system when compared to growth in culture media. In planta
      growth is closest to a real interaction condition and captures the complexity of
      the plant cell environment; however, this system has some limitations. The main
      finding of our work is that the addition of plant extract to XVM1 medium results
      in a gene expression profile that better matches the in planta profile, when
      compared with the XVM1 medium alone, giving support to the use of plant extract
      to study pathogenicity mechanisms in Xanthomonas.

PMID- 29040468
TI  - From Eisenhower's heart attack to modern management: a true success story!

PMID- 29040470
TI  - Aorto-left ventricular tunnel: an unusual aortic flow, from images to modelling.

PMID- 29040469
TI  - The commercialization of traditional medicine in modern Cambodia.
AB  - Globally, traditional medicine has long been used to address relatively common
      illness, mental ill health and during childbirth and post-natal care. However,
      traditional medicine is primarily provided by the private sector and it is
      unclear how far expenditures on traditional medicine contribute to household
      impoverishment. A life history method was used to understand the health seeking
      experience of 24 households over the last 60 years in Cambodia, a country with
      high out-of-pocket expenditures for health. The life histories suggest that
      traditional medicine in Cambodia has been undergoing a process of
      commercialization, with significant impacts on poor households. In the earlier
      lives of respondents, payments for traditional medicine were reported to have
      been flexible, voluntary or appropriate to patients' financial means. In
      contrast, contemporary practitioners appear to seek immediate cash payments that
      have frequently led to considerable debt and asset sales by traditional medicine
      users. Given traditional medicine's popularity as a source of treatment in
      Cambodia and its potential to contribute to household impoverishment, we suggest
      that it needs to be included in a national conversation about achieving Universal
      Health Coverage in the country.

PMID- 29040471
TI  - Endometriosis fertility index predicts live births following surgical resection
      of moderate and severe endometriosis.
AB  - STUDY QUESTION: Can live birth be accurately predicted following surgical
      resection of moderate-severe (Stage III-IV) endometriosis? SUMMARY ANSWER: Live
      births can accurately be predicted with the endometriosis fertility index (EFI),
      with adnexal function being the most important factor to predict non-assisted
      reproductive technology (non-ART) fertility or the requirement for ART
      (www.endometriosisefi.com). WHAT IS KNOWN ALREADY: Fertility prognosis is
      important to many women with severe endometriosis. Controversy persists regarding
      optimal post-operative management to achieve pregnancy and the counselling of
      patients regarding duration of conventional treatments before undergoing ART. The
      EFI is reported to correlate with expectant management pregnancy rate, although
      external validation has been performed without specifically addressing fertility
      in women with moderate and severe endometriosis. STUDY DESIGN, SIZE, DURATION:
      Retrospective cohort study of 279 women from September 2001 to June 2016.
      PARTICIPANTS/MATERIALS, SETTINGS, METHODS: We included women undergoing
      laparoscopic resection of Stage III-IV endometriosis who attempted pregnancy post
      operatively. The EFI was calculated based on detailed operative reports and
      surgical images. Fertility outcomes were obtained by direct patient contact.
      Kaplan-Meier model, log rank test and Cox regression were used for analyses. MAIN
      RESULTS AND THE ROLE OF CHANCE: The follow-up rate was 84% with a mean duration
      of 4.1 years. A total of 147 women (63%) had a live birth following surgery, 94
      of them (64%) without ART. The EFI was highly associated with live births (P <
      0.001): for women with an EFI of 0-2 the estimated cumulative non-ART live birth
      rate at five years was 0% and steadily increased up to 91% with an EFI of 9-10,
      while the proportion of women who attempted ART and had a live birth, steadily
      increased from 38 to 71% among the same EFI strata (P = 0.1). A low least
      function score was the most significant predictor of failure (P = 0.003),
      followed by having had a previous resection (P = 0.019) or incomplete resection
      (P = 0.028), being older than 40 compared to <35 years of age (P = 0.027), and
      having leiomyomas (P = 0.037). LIMITATIONS REASONS FOR CAUTION: The main
      limitation of this study is its retrospective design. Imprecision was higher with
      low EFI due to smaller sample size in this subgroup. Finally, the EFI is somewhat
      subjective and could be prone to intra- and inter-observer variations. WIDER
      IMPLICATIONS OF THE FINDINGS: Women with a high EFI score have excellent
      fertility prognosis and may be advised to try to become pregnant with timed
      intercourse compared to women with a low score, for which prompt referral to ART
      seems more reasonable. Other prognostic factors can be used to guide the
      management of women with an intermediate EFI score. These data follow women over
      many years post-resection and represent longitudinal fertility data rarely
      demonstrated in such a cohort. The location and impact of lesions on the ability
      of the adnexa to function seems crucial for the fertility prognosis and should be
      further investigated. STUDY FUNDING/COMPETING INTEREST(S): This study was funded
      by the GRACE Research funds. S.M.-L. is the recipient of a Training Award from
      the Fonds de Recherche Quebec-Sante. D.A. is the primary author of the
      Endometriosis Fertility Index. All authors have no conflicts of interest to
      declare. TRIAL REGISTRATION NUMBER: N/A.

PMID- 29040473
TI  - miRNA-based antiarrhythmics after myocardial ischaemic injury: Authors' reply.

PMID- 29040472
TI  - Optogenetic Modulation of a Minor Fraction of Parvalbumin-Positive Interneurons
      Specifically Affects Spatiotemporal Dynamics of Spontaneous and Sensory-Evoked
      Activity in Mouse Somatosensory Cortex in Vivo.
AB  - Parvalbumin (PV) positive interneurons exert strong effects on the neocortical
      excitatory network, but it remains unclear how they impact the spatiotemporal
      dynamics of sensory processing in the somatosensory cortex. Here, we
      characterized the effects of optogenetic inhibition and activation of PV
      interneurons on spontaneous and sensory-evoked activity in mouse barrel cortex in
      vivo. Inhibiting PV interneurons led to a broad-spectrum power increase both in
      spontaneous and sensory-evoked activity. Whisker-evoked responses were
      significantly increased within 20 ms after stimulus onset during inhibition of PV
      interneurons, demonstrating high temporal precision of PV-shaped inhibition.
      Multiunit activity was strongly enhanced in neighboring cortical columns, but not
      at the site of transduction, supporting a central and highly specific role of PV
      interneurons in lateral inhibition. Inversely, activating PV interneurons
      drastically decreased spontaneous and whisker-evoked activity in the principal
      column and exerted strong lateral inhibition. Histological assessment of
      transduced cells combined with quantitative modeling of light distribution and
      spike sorting revealed that only a minor fraction (~10%) of the local PV
      population comprising no more than a few hundred neurons is optogenetically
      modulated, mediating the observed prominent and widespread effects on neocortical
      processing.

PMID- 29040474
TI  - Co-occurrence of genes for aerobic and anaerobic biodegradation of dichloroethane
      in organochlorine-contaminated groundwater.
AB  - 1,2-Dichloroethane (DCA) is a problematic groundwater pollutant. Factors
      influencing the distribution and activities of DCA-degrading bacteria are not
      well understood, which has hampered their application for bioremediation. Here,
      we used quantitative PCR to investigate the distribution of putative DCA
      dehalogenating bacteria at a DCA-impacted site in Sydney (Australia). The
      dehalogenase genes dhlA, tceA and bvcA were detected in all groundwater samples
      (n = 15), while vcrA was found in 11/15 samples. The 16S rRNA gene sequences
      specific to the dehalogenating genera Dehalobacter, Desulfitobacterium and
      Dehalogenimonas were detected in 15/15, 13/15 and 13/15 samples, respectively,
      while Dehalococcoides sequences were found in 9/15 samples. The tceA, bvcA and
      vcrA genes occurred in the same samples as Dehalococcoides and Dehalobacter.
      Microcosm experiments confirmed the presence of bacteria capable of
      dechlorination under anoxic conditions. The abundance of the dhlA gene, which is
      found in hydrolytic DCA degraders, was positively correlated to the DCA
      concentration, and was unexpectedly most abundant in samples with low oxygen
      conditions. A dhlA-containing bacterium isolated from the site (Xanthobacter EL8)
      was capable of anaerobic growth on DCA under denitrifying conditions. The
      presence of diverse DCA-dehalogenating bacteria at this site indicates that
      natural attenuation or biostimulation could be valid approaches for site cleanup.

PMID- 29040475
TI  - From Nose to Memory: The Involuntary Nature of Odor-evoked Autobiographical
      Memories in Alzheimer's Disease.
AB  - Research suggests that odors may serve as a potent cue for autobiographical
      retrieval. We tested this hypothesis in Alzheimer's disease (AD) and investigated
      whether odor-evoked autobiographical memory is an involuntary process that shares
      similarities with music-evoked autobiographical memory. Participants with mild AD
      and controls were asked to retrieve 2 personal memories after odor exposure,
      after music exposure, and in an odor-and music-free condition. AD participants
      showed better specificity, emotional experience, mental time travel, and
      retrieval time after odor and music exposure than in the control condition.
      Similar beneficial effects of odor and music exposure were observed for
      autobiographical characteristics (i.e., specificity, emotional experience, and
      mental time travel), except for retrieval time which was more improved after odor
      than after music exposure. Interestingly, regression analyses suggested executive
      involvement in memories evoked in the control condition but not in those evoked
      after music or odor exposure. These findings suggest the involuntary nature of
      odor-evoked autobiographical memory in AD. They also suggest that olfactory cuing
      could serve as a useful and ecologically valid tool to stimulate autobiographical
      memory, at least in the mild stage of the disease.

PMID- 29040477
TI  - The Critical Importance of Sampling Fraction to Inferences of Mycobacterium
      tuberculosis Transmission.

PMID- 29040476
TI  - National responses to global health targets: exploring policy transfer in the
      context of the UNAIDS '90-90-90' treatment targets in Ghana and Uganda.
AB  - Global health organizations frequently set disease-specific targets with the goal
      of eliciting adoption at the national-level; consideration of the influence of
      target setting on national policies, programme and health budgets is of benefit
      to those setting targets and those intended to respond. In 2014, the Joint United
      Nations Programme on HIV/AIDS set 'ambitious' treatment targets for country
      adoption: 90% of HIV-positive persons should know their status; 90% of those on
      treatment; 90% of those achieving viral suppression. Using case studies from
      Ghana and Uganda, we explore how the target and its associated policy content
      have been adopted at the national level. That is whether adoption is in rhetoric
      only or supported by programme, policy or budgetary changes. We review 23 (14
      from Ghana, 9 from Uganda) national policy, operational and strategic documents
      for the HIV response and assess commitments to '90-90-90'. In-person semi
      structured interviews were conducted with purposively sampled key informants (17
      in Ghana, 20 in Uganda) involved in programme-planning and resource allocation
      within HIV to gain insight into factors facilitating adoption of 90-90-90.
      Interviews were transcribed and analysed thematically, inductively and
      deductively, guided by pre-existing policy theories, including Dolowitz and
      Marsh's policy transfer framework to describe features of the transfer and the
      Global Health Advocacy and Policy Project framework to explain observations.
      Regardless of notable resource constraints, transfer of the 90-90-90 targets was
      evident beyond rhetoric with substantial shifts in policy and programme
      activities. In both countries, there was evidence of attempts to minimize
      resource constraints by seeking programme efficiencies, prioritization of
      programme activities and devising domestic financing mechanisms; however,
      significant resource gaps persist. An effective health network, comprised of
      global and local actors, mediated the adoption and adaptation, facilitating a
      shift in the HIV programme from 'business as usual' to approaches targeting
      geographies and populations.

PMID- 29040478
TI  - Corrigendum.

PMID- 29040479
TI  - Quality of life following esophagectomy with three-field lymphadenectomy for
      carcinoma, focusing on its relationship to vocal cord palsy.
AB  - To clarify the quality of life of patients who underwent esophagectomy for
      carcinoma by right thoracotomy, laparotomy and cervical anastomosis, 116 patients
      who were cancer free at the time of mailing a questionnaire were analyzed. A
      significant decrease in vital capacity for 3 years postoperatively, as well as in
      the percentage of ideal body weight, between 3 and 5 years were observed in 57
      patients with three-field lymphadenectomy. Patients' quality of life undergoing
      three-field dissection was worse than those with less radical lymphadenectomy (59
      cases) in terms of the performance status and difficulty in talking at 60 months
      or more postoperatively. Around 20% of all patients reported severe hoarseness
      due to permanent recurrent nerve paralysis, resulting in poor quantity of food
      intake at 24 months or less postoperatively and restricted daily activity and
      difficulty in talking at 60 months or more after the operation. When a patient
      suffers from vocal cord insufficiency caused by permanent paralysis of the
      recurrent nerve, early treatment before discharge from the hospital should be
      performed to improve the quality of life of such a patient.

PMID- 29040480
TI  - CYFRA 21-1 as a tumor marker for squamous cell carcinoma of the esophagus.
AB  - This study assessed the clinical value of CYFRA 21-1 in comparison with squamous
      cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and carbohydrate
      antigen 19-9 (CA19-9) in patients with esophageal squamous cell carcinoma. In 112
      primary cancer patients, the diagnostic sensitivity of CYFRA 21-1 (33.9%) was
      superior to SCC-Ag (28.6%), CEA (12.5%), and CA19-9 (6.3%). Levels of CYFRA 21-1
      were closely correlated with TNM stage and were below the cutoff value in all 21
      patients with stage I disease. All 38 patients with a CYFRA 21-1 level over the
      cutoff value among the 80 patients who underwent esophagectomy had lymph node
      metastases (pNl). A correlation was found between CYFRA 21-1 levels and clinical
      response in serial measurements of 21 patients who received chemotherapy or chemo
      radiotherapy. Our findings suggest that CYFRA 21-1 is not useful for diagnosis,
      but that it is valuable for monitoring the efficacy of therapy.

PMID- 29040481
TI  - The value of neck drain in esophageal surgery: a randomized trial.
AB  - The use of surgical drains in certain clean elective operations remains
      controversial. To evaluate the role of closed-suction drain for an esophageal
      anastomosis in the neck, we conducted a randomized, controlled study in 40
      patients with esophageal carcinoma who underwent esophagectomy with an esophageal
      anastomosis in the neck, half of whom had a neck drain inserted at the end of
      operation. The median (range) duration of drainage was 46 hours (36 to 88 hours).
      The median (range) amount of drainage was 63 ml (15 to 210 ml). There was no
      incidence of haematoma or seroma formation in both the drained and non-drained
      groups. Anastomotic leakage did not occur in any patient. The benefits of closed
      suction neck drain could not be demonstrated. Routine use of neck drain for
      esophageal anastomosis in the neck is not necessary.

PMID- 29040482
TI  - Strategies to reduce pulmonary complications after transhiatal esophagectomy.
AB  - Background: By eliminating a thoracotomy, transhiatal esophagectomy (THE) is
      purported to reduce postoperative pulmonary complications. However, data from
      many early series do not support this contention, documenting pulmonary
      complications in up to 50% of patients and pneumonia in 5%-20%. Since 1990, we
      have implemented a management strategy designed to maximize airway protection in
      the postoperative period. The purpose of this study was to determine the current
      incidence of pulmonary complications after transhiatal esophagectomy without
      thoracotomy. Patients and Methods: From 1990 to 1995, 101 consecutive patients
      underwent THE. Surgical indications were esophageal carcinoma (90 patients) and
      Barrett mucosa with high-grade epithelial dysplasia (11 patients). Mean age was
      60.2 +/- 1.2 years; 89 patients were male. Eighty-two patients were smokers and
      26 had chronic obstructive pulmonary disease (COPD). Sixty-five patients were
      American Society of Anesthesiologists risk score 3 or 4. Postoperatively, all
      patients were managed according to a standardized clinical pathway that included
      overnight mechanical ventilation, chest physiotherapy, video pharyngo-esophagram
      postoperative day 6 or 7, and graduated post-esophagectomy therapeutic diet after
      acceptable esophagram. Results: Pulmonary complications were classified as major
      or minor depending upon whether or not a change in therapy was required. Ten
      patients (10%) had 11 major pulmonary complications. These included pneumonia
      (3), pleural effusion requiring drainage (4), exacerbation of COPD (2), and mucus
      plug requiring bronchoscopy or intubation (2). Minor pulmonary complications
      identified by chest film were atelectasis (97), pleural effusion (85), and
      pneumothorax (3). Patients with major pulmonary complications were older (69.3 +/
      9.8 vs. 59.2 +/- 12.1 years, p < .02) and more likely to have COPD (70% vs. 21%,
      p < .005) than those with only minor complications. There were 3 operative
      deaths; 2 caused by pneumonia and 1 by fungal sepsis in a patient who had
      exacerbation of COPD. Mean hospital length of stay was 13.1 +/- 1.4 days.
      Conclusions: Minor pulmonary complications identified by chest film occur in
      nearly all patients undergoing THE. Strict adherence to a management protocol
      designed to maximize airway protection in the postoperative period results in a
      10% incidence of major pulmonary complications. Older patient age and COPD are
      risk factors for major pulmonary complications after THE. Although pneumonia is
      uncommon, it remains the most frequent cause of death after THE.

PMID- 29040483
TI  - Results of surgical treatment of cervical esophageal diverticula.
AB  - On the basis of 20 years' experience, the authors present the immediate and long
      term results of operative treatment of Zenker's diverticulum. Comparison of two
      methods of surgery - diverticulopexia (in 21 patients) and excision (in 16), both
      associated with upper esophageal sphincter myotomy - shows good immediate and
      longterm results (from 1 to 19 years), with disappearance of symptoms (dysphagia)
      in all patients. There was no perioperative mortality. Postoperative
      complications were most commonly of pulmonary origin and were observed in a third
      of patients in both groups. In two patients from the group treated with excision,
      a leak from the suture line occurred, which healed spontaneously. These two
      patients had transient dysphagia in the postoperative period. On the basis of
      this analysis, the authors conclude that diverticulopexia is a safer surgical
      procedure than excision, giving less complications and a very good long-term
      functional result.

PMID- 29040484
TI  - Esophagocardioplasty, vagotomy-antrectomy and Roux-en-Y gastrojejunostomy:
      indication in cases with severe esophageal motor disfunction.
AB  - Almost 10% of patients with Crest syndrome associated with severe
      gastroesophageal reflux and 5-10% of patients with failed cardiomyotomy for
      achalasia present with cardial or distal esophageal organic stricture. Some of
      these cases are poor risk patients for surgery and therefore the surgeon must
      offer a safe procedure with low morbimortality, keeping in mind the
      pathophysiological motor pattern of these patients.In order to treat the
      stricture to improve the esophageal transit we treated patients with
      esophagocardioplasty associated with vagotomy-antrectomy and Roux-en-Y
      gastrojejunostomy, thereby avoiding the potential acid or biliary reflux in poor
      risk patients in whom esophagectomy would be a very deleterious procedure. All
      four patients had a good postoperative evolution and late control demonstrated
      good esophagogastric transit with no postoperative esophagitis.

PMID- 29040485
TI  - Esophageal duplication cyst: case report and review of the literature.

PMID- 29040486
TI  - Delayed traumatic rupture of the thoracic aorta into the esophagus.
AB  - A case of delayed rupture of the thoracic aorta into the esophagus after blunt
      thoracic injury is reported. It involved a hemodynamically stable 18-year-old
      male patient without any clinical or radiological signs to indicate aortic
      injury. Aortoesophageal fistula presented in the fifth post traumatic day, with a
      sudden dyspnea episode, intraperitoneal hemorrhage and lower gastrointestinal
      bleeding, due to intraperitoneal and intragastric rupture of intramural
      esophageal hematoma.

PMID- 29040487
TI  - Pedunculated liposarcoma of the esophagus.
AB  - Polypoid tumours of the esophagus present diagnostic and therapeutic problems.
      Liposarcomas are infrequent among them. We report a recent case. A 73-year-old
      male patient was seen in May 1995 in the Ear, Nose and Throat (ENT) Department,
      Clinica Modelo de Moron, with intermittent dysphagia and dyspnoea due to
      recurrent vomiting. A laryngeal lineal tomography showed a subglottic obstruction
      due to extrinsic compression. The patient was referred to the Gastroenterology
      Department, where an upper gastrointestinal (upper GI) series demonstrated mega
      esophagus with abundant retained food. Endoscopy showed a large intraluminal mass
      covered by normal mucosa which arose on the posterior wall. Videofluoroscopy and
      chest CT diagnosed a probable polypoid lipoma due to its densitometric
      characteristics. The tumour was resected by left cervicotomy and left
      esophagotomy. The patient's progress to date is favourable. Pathology studies
      showed a well-differentiated liposarcoma. According to the literature, the first
      case was reported in 1983, and ours is only the seventh case in the world to be
      documented.

PMID- 29040489
TI  - Palliation of anastomotic tumor recurrence after esophagectomy and gastric
      transposition: cervico-mediastinal resection and reconstruction by using a free
      jejunal transplant.

PMID- 29040488
TI  - Tuberculosis of the esophagus.
AB  - We report a case of a patient with esophageal tuberculosis, a very uncommon form
      of extrapulrhonar tuberculosis. Initially, because of constitutional
      symptomatology and radiological findings of mediastinal lymph node enlargement,
      lymphoma was considered. However, the endoscopic findings of ulcerative masses
      and a sinus tract revealed by esophagram were suspicious of tuberculous origin.
      Diagnosis was achieved after bacterial examination of smear samples from
      esophageal ulcers that revealed bacillus tuberculous and histological
      demonstration of caseating granulomas in cervical lymph nodes. Tuberculous
      mediastinal lymphadenitis was thought to be source of the spread to esophagus.The
      patient was successfully treated with a three antituberculous drugs regimen. In
      spite of its rarity, even in patients without risk factors, the diagnosis would
      be considered in the differential diagnosis of uncertain esophageal lesions.

PMID- 29040490
TI  - Proceedings from an international conference on ablation therapy for Barrett's
      mucosa: Brittany, France, 31 August - 2 September 1997.
AB  - The increasing incidence of adenocarcinoma of the lower esophagus and cardia
      arising in Barrett's metaplastic epithelium continues to be of great concern
      because medical and surgical efforts to reverse the process have been
      disappointing. A potential answer to the problem is removal of the metaplastic
      epithelium. Modern technology has introduced physical and chemical modalities
      which facilitate ablation of the neo-epithelium endoscopically. These techniques
      have been used in several centers, and preliminary results are encouraging. This
      report summarizes the proceedings of an international symposium on ablative
      therapy held in Brittany, France in August 1997.Twenty-eight speakers contributed
      to the talks on the pathology, pathogenesis, current therapy experimental studies
      and clinical experience of ablation of Barrett's esophagus.

PMID- 29040491
TI  - The influence of the transposed stomach through the posterior mediastinum on the
      respiratory forced expiratory volume and forced vital capacity in patients with
      resected esophageal cancer.
AB  - Although the use of the posterior mediastinum and the stomach as a reconstruction
      option after esophagectomy has large acceptance all over the world, there are
      concerns about the potential respiratory impairment it could cause. We
      prospectively studied 35 patients regarding the forced expiratory volume and
      vital capacity. The patients were studied preoperatively and between the 45th and
      60th postoperative days. The value of both parameters decreased, although they
      were still within normal clinical ranges. We concluded that this type of
      reconstruction does not harm the patients regarding the respiratory flow rates.

PMID- 29040492
TI  - Foreign body impaction in the esophagus: are there underlying motor disorders?
AB  - Results: Compared with the control group, the impacted subjects presented marked
      reduction in amplitude and duration of esophageal contraction in the proximal
      esophagus. Conclusions: These motor disorders could be responsible for the
      foreign body impaction in the esophagus. However, we believe this patient group
      should be further studied by 24-hour esophageal manometry to reach a more
      accurate diagnosis by studying each patient's entire circadian cycle.

PMID- 29040493
TI  - Releasing the "GENI": integrating authentic microbial genomics research into the
      classroom through GENI-ACT.
AB  - The integration of genomics research into the undergraduate biology curriculum
      provides students with the opportunity to become familiar with bioinformatics
      tools and answer original research questions. Our purpose with this research
      project was to upscale the research experience through integration with classroom
      experience giving students access to authentic research projects. Students
      annotated 60 predicted ABC genes of Methanothermobacter thermautotrophicus and
      Methanobacterium sp. SWAN-1, and they were required to present a research poster
      to demonstrate their understanding of the project. During this research project a
      number of tests, assessments and surveys were conducted to assess familiarity
      with technical and conceptual understanding of genome annotation, satisfaction
      with annotation instruction, gain in bioinformatics research skills, scientific
      communications skills and increased student interest in research. We found that
      students gained significant skills in bioinformatics, specifically genome
      annotation skills and also gained confidence in their abilities to carry out
      scientific research. As a result of this authentic undergraduate research
      experience under-represented students were motivated to pursue future careers in
      STEM fields.

PMID- 29040494
TI  - Beyond Reward Prediction Errors: Human Striatum Updates Rule Values During
      Learning.
AB  - Humans naturally group the world into coherent categories defined by membership
      rules. Rules can be learned implicitly by building stimulus-response associations
      using reinforcement learning or by using explicit reasoning. We tested if the
      striatum, in which activation reliably scales with reward prediction error, would
      track prediction errors in a task that required explicit rule generation. Using
      functional magnetic resonance imaging during a categorization task, we show that
      striatal responses to feedback scale with a "surprise" signal derived from a
      Bayesian rule-learning model and are inconsistent with RL prediction error. We
      also find that striatum and caudal inferior frontal sulcus (cIFS) are involved in
      updating the likelihood of discriminative rules. We conclude that the striatum,
      in cooperation with the cIFS, is involved in updating the values assigned to
      categorization rules when people learn using explicit reasoning.

PMID- 29040495
TI  - Applying sequence clustering techniques to explore practice-based ambulatory care
      pathways in insurance claims data.
AB  - Background: Care pathways are a widely used mean to ensure well-coordinated and
      high quality care by defining the optimal timing and interval of health services
      for a specific indication. However, evidence on common sequences of services
      actually followed by patients has rarely been quantified. This study aims to
      explore whether sequence clustering techniques can be used to empirically
      identify typical treatment sequences in ambulatory care for heart failure (HF)
      patients and compare their effectiveness. Methods: Routine data of HF patients
      were provided by a large statutory sickness fund in Germany from 2009 until 2011.
      Events were categorized by either (i) the specialty of the physician, (ii) the
      type of service/procedure provided and (iii) the medication prescribed.
      Similarities between sequences were measured using the 'longest common
      subsequence' (LCS). The k-medoids clustering algorithm was applied to identify
      distinct subgroups of sequences. We used logistic regression to identify the most
      effective sequences for avoiding hospitalizations. Results: Treatment data of 982
      incident HF patients were analyzed to identify typical treatment sequences. The
      cluster analysis revealed three distinct clusters of specialty sequences, four
      clusters of procedure sequences and four clusters of prescription sequences.
      Clusters differed in terms of timing and interval of physician visits, procedures
      and drug prescriptions as well as comorbidities and HF hospitalization rates. We
      found no significant association between cluster membership and HF
      hospitalization. Conclusions: Sequence clustering techniques can be used as an
      explorative tool to systematically extract, describe compare and analyze
      treatment sequences and associated characteristics.

PMID- 29040496
TI  - Changes in platelet Bax levels contribute to impaired platelet response to
      thrombin after cardiopulmonary bypass: prospective observational clinical and
      laboratory investigations.
AB  - Background: Anucleate platelets can undergo apoptosis in response to various
      stimuli, as do nucleated cells. Cardiopulmonary bypass (CPB) causes platelet
      dysfunction and can also activate platelet apoptotic pathways. We therefore
      evaluated time-dependent changes in blood platelet Bax (a pro-apoptotic molecule)
      levels and platelet dysfunction after cardiac surgery. Methods: We assessed blood
      samples obtained from subjects having on-pump or off-pump coronary artery bypass
      graft surgery ( n =20 each). We also evaluated the in vitro effects of platelet
      Bax increase in eight healthy volunteers. Results: Thrombin-induced platelet
      calcium mobilisation and platelet-surface glycoprotein Ib (GPIb) expression were
      lowest at weaning from CPB and did not recover on postoperative day one. On-pump
      surgery increased platelet expression of Bax, especially the oligomerised form,
      along with translocation of Bax from the cytosol to mitochondria and platelet
      surface tumour necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE)
      expression. In contrast, mitochondrial cytochrome c expression was reduced. While
      similar in direction, the magnitude of the observed changes was smaller in
      patients having off-pump surgery. In vitro , a cell-permeable Bax peptide
      increased platelet Bax expression to the same extent seen during bypass and
      produced similar platelet changes. These apoptotic-like changes were largely
      reversed by Bcl-xL pre-administration, and were completely reversed by combined
      application of inhibitors that stabilise outer mitochondrial membrane
      permeability and TACE. Conclusions: CPB increases platelet Bax expression, which
      contributes to reduced platelet-surface GPIb expression and thrombin-induced
      platelet calcium changes. These changes in platelet apoptotic signalling might
      contribute to platelet dysfunction after CPB. Clinical trial registration: UMIN
      Clinical Trials Registry (number UMIN000006033).

PMID- 29040497
TI  - The Association Between Fall Frequency, Injury Risk, and Characteristics of Falls
      in Older Residents of Long-Term Care: Do Recurrent Fallers Fall More Safely?
AB  - Background: Although a fall is a necessary prerequisite to a fall-related injury,
      previous studies suggest that frequent fallers are at lower injury risk for a
      given fall. We tested the hypotheses that differences in protective responses or
      the circumstances of falls underlie differences in injury risk with fall
      frequency. Methods: We analyzed video footage of 897 falls experienced by 220
      long-term care residents (mean age 82 +/- 9 years) to identify the cause of
      imbalance, activity leading to falling, direction of fall initiation, balance
      recovery and fall protective responses, and occurrence of impact to the head or
      hip. We further obtained injury information from the facilities' fall
      registration. We used generalized estimating equation models to examine the
      association between quartiles of fall frequency, injury risk, and fall
      characteristics. Results: Residents with the highest fall frequency group (Q4;
      >=5.6 falls/year) were less likely to sustain an injury per fall. They were less
      likely to fall during walking and more likely to fall during stand-to-sit
      transfers. Residents in the lowest fall frequency group (Q1; <1.15 falls/year)
      were more likely to fall during walking, and walking was associated with an
      increased risk for injury. Conclusion: When compared to less frequent fallers,
      more frequent fallers had a lower risk for injury per fall. This appeared to be
      explained by differences in the circumstances of falls, and not by protective
      responses. Injury prevention strategies in long-term care should target both
      frequent and infrequent fallers, as the latter are more mobile and apt to sustain
      injury.

PMID- 29040498
TI  - Genome stability of bovine in vivo-conceived cleavage-stage embryos is higher
      compared to in vitro-produced embryos.
AB  - STUDY QUESTION: Is the rate and nature of chromosome instability (CIN) similar
      between bovine in vivo-derived and in vitro-cultured cleavage-stage embryos?
      SUMMARY ANSWER: There is a major difference regarding chromosome stability of in
      vivo-derived and in vitro-cultured embryos, as CIN is significantly lower in in
      vivo-derived cleavage-stage embryos compared to in vitro-cultured embryos. WHAT
      IS KNOWN ALREADY: CIN is common during in vitro embryogenesis and is associated
      with early embryonic loss in humans, but the stability of in vivo-conceived
      cleavage-stage embryos remains largely unknown. STUDY DESIGN, SIZE, DURATION:
      Because human in vivo preimplantation embryos are not accessible, bovine (Bos
      taurus) embryos were used to study CIN in vivo. Five young, healthy, cycling
      Holstein Friesian heifers were used to analyze single blastomeres of in vivo
      embryos, in vitro embryos produced by ovum pick up with ovarian stimulation (OPU
      IVF), and in vitro embryos produced from in vitro matured oocytes retrieved
      without ovarian stimulation (IVM-IVF). PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Single blastomeres were isolated from embryos, whole-genome amplified and
      hybridized on Illumina BovineHD BeadChip arrays together with the bulk DNA from
      the donor cows (mothers) and the bull (father). DNA was also obtained from the
      parents of the bull and from the parents of the cows (paternal and maternal
      grandparents, respectively). Subsequently, genome-wide haplotyping and copy
      number profiling was applied to investigate the genomic architecture of 171
      single bovine blastomeres of 16 in vivo, 13 OPU-IVF and 13 IVM-IVF embryos. MAIN
      RESULTS AND THE ROLE OF CHANCE: The genomic stability of single blastomeres in
      both of the in vitro-cultured embryo cohorts was severely compromised (P <
      0.0001), and the frequency of whole chromosome or segmental aberrations was
      higher in embryos produced in vitro than in embryos derived in vivo. Only 18.8%
      of in vivo-derived embryos contained at least one blastomere with chromosomal
      anomalies, compared to 69.2% of OPU-IVF embryos (P < 0.01) and 84.6% of IVM-IVF
      embryos (P < 0.001). LARGE SCALE DATA: Genotyping data obtained in this study has
      been submitted to NCBI Gene Expression Omnibus (GEO; accession number GSE95358).
      LIMITATIONS REASONS FOR CAUTION: There were two main limitations of the study.
      First, animal models may not always reflect the nature of human embryogenesis,
      although the use of an animal model to investigate CIN was unavoidable in our
      study. Second, a limited number of embryos were obtained, therefore more studies
      are warranted to corroborate the findings. WIDER IMPLICATIONS OF THE FINDINGS:
      Although CIN is also present in in vivo-developed embryos, in vitro procedures
      exacerbate chromosomal abnormalities during early embryo development. Hence, the
      present study highlights that IVF treatment compromises embryo viability and
      should be applied with care. Additionally, our results encourage to refine and
      improve in vitro culture conditions and assisted reproduction technologies. STUDY
      FUNDING/COMPETING INTEREST(S): The study was funded by the Agency for Innovation
      by Science and Technology (IWT) (TBM-090878 to J.R.V. and T.V.), the Research
      Foundation Flanders (FWO; G.A093.11 N to T.V. and J.R.V. and G.0392.14 N to
      A.V.S. and J.R.V.), the European Union's FP7 Marie Curie Industry-Academia
      Partnerships and Pathways (IAPP, SARM, EU324509 to J.R.V., T.V., O.T, A.D., A.S.
      and A.K.) and Horizon 2020 innovation programme (WIDENLIFE, 692065 to J.R.V.,
      O.T., T.V., A.K. and A.S.). M.Z.E., J.R.V. and T.V. are co-inventors on a patent
      application ZL913096-PCT/EP2014/068315-WO/2015/028576 ('Haplotyping and copy
      number typing using polymorphic variant allelic frequencies'), licensed to
      Cartagenia (Agilent Technologies).

PMID- 29040499
TI  - Sharing health information online in South Korea: motives, topics, and
      antecedents.
AB  - This study aimed to examine the motives, topics and antecedents for sharing
      health information online among Korean Internet users. Eight hundred adults
      completed a web-based survey exploring the motives; topics; physical, cognitive,
      affective and environmental factors; and experiences relating to sharing health
      information online. The motives for not sharing information included information
      absence and inappropriateness. The most preferred topic was disease. Good
      subjective health was significantly associated with frequent information sharing
      while individuals with a history of disease involving themselves or family
      members were more likely to share health information than were those without such
      a history. Further, a higher level of depressed mood was related to a higher
      level of sharing. Internet-related self-efficacy and trust in information
      delivery channels were positively related to sharing. Future research could
      extend the factors related to information sharing to include the evaluation of
      shared information.

PMID- 29040500
TI  - Chlamydia trachomatis plasmid-encoded protein pORF5 protects mitochondrial
      function by inducing mitophagy and increasing HMGB1 expression.
AB  - Chlamydia trachomatis, an obligate intracellular pathogen, has various effective
      strategies to regulate host cell death signalling pathways that ensure completion
      of their growth cycle. Mitochondrial autophagy (mitophagy) is responsible for
      elimination of dysfunctional and impaired mitochondria, and this process plays a
      critical role in cell survival via restriction of the mitochondrial apoptotic
      pathway. However, the specific molecular mechanisms are not entirely understood.
      In the present study, we observed that pORF5 plasmid protein of C. trachomatis
      plays a crucial role in attenuating mitochondrial dysfunction and apoptosis.
      Knockdown high mobility group box 1 (HMGB1) by lentivirus suppressed pORF5
      induced mitophagy and increased apoptosis, implying that pORF5 may participate in
      cell death signalling pathways via up-regulation of HMGB1. Thus, we concluded
      that up-regulation of HMGB1 is a pivotal event for C. trachomatis that
      manipulates mitophagy and apoptosis in order to establish a favourable
      environment supportive of Chlamydial growth, which should further promote our
      understanding of Chlamydial pathogenic mechanisms.

PMID- 29040501
TI  - Tissue damage induced midgut stem cell proliferation and microbial dysbiosis in
      Spodoptera litura.
AB  - In the past decade, gut microbiota has come to the fore in search for the cause
      of disregulation in intestinal homeostasis. Here, we report a possible link
      between gut microbial dynamics and stress-inducing factors using the leaf worm
      moth Spodoptera litura as a model organism. Investigation reveals that S. litura
      exhibits dysbiosis i.e. alteration in the gut microbiota composition that might
      induce or suppress inflammation upon exposure to dextran sulfate sodium salt, a
      tissue damaging agent (DSS, 40 kD). It primarily corresponds to an expansion of
      the bacterial phylotypes Enterobacter sp., Pseudomonas sp., Escherichia sp. and
      Acinetobacter sp. belonging to subclass Gammaproteobacteria. To assess the role
      played by gut residents in midgut inflammation, we re-colonized the axenic
      insects with Pseudomonas, Enterobacter and Acinetobacter individually. We
      observed that Pseudomonas and Enterobacter monoassociated insects exhibit
      inflammatory effects like damage to gut epithelium and hyperproliferation of stem
      cells under stress conditions. Conversely, Acinetobacter promotes fitness in
      larvae and reduces inflammatory effects of DSS. However, we failed to detect
      phenotypic inflammatory changes like midgut epithelium damage and stem cell
      proliferation in axenic insects reared on DSS-supplemented diet. Our results
      highlight that gut commensals that apparently remain low in abundance and benign
      under typical conditions can exert modulatory (positive or negative) effects on
      host fitness in the presence of stimulator.

PMID- 29040502
TI  - Comparative genomics of the genus Desulfitobacterium.
AB  - The Desulfitobacterium genus comprises anaerobic Gram-positive bacteria, of which
      the majority are facultative organohalide respirers. We here present the genomes
      of eight strains of Desulfitobacterium spp., including five strains of
      Desulfitobacterium hafniense, one strain each from D. dichloroeliminans and D.
      metallireducens, and one strain that had not been assigned to any species prior
      to this study. The newly sequenced genomes were compared with four previously
      published desulfitobacterial genomes. The average genome sizes are 5.5, 4.3 and
      3.4 Mbp for D. hafniense, D. dehalogenans and D.
      dichloroeliminans/metallireducens, respectively. The genomes encode up to seven
      reductive dehalogenases, the genomes of both D. hafniense DP7 and D.
      metallireducens 853-15AT did not encode any reductive dehalogenase. The latter
      result was a surprise as D. metallireducens 853-15AT has been reported to carry
      out organohalide respiration. Unlike reported for the pceABCT gene cluster, the
      other reductive dehalogenase gene clusters do not show any signs of being
      genetically mobile. All analyzed desulfitobacterial genomes encode a complete
      cobalamin synthesis pathway. A menaquinone synthesis pathway was found in all
      strains except D. dichloroeliminans DCA1T. The detailed analysis of the genome
      sequence of 12 desulfitobacteria from four different species confirmed that this
      genus has an extremely large metabolic repertoire.

PMID- 29040504
TI  - Implementing multiple intervention strategies in Dutch public health-related
      policy networks.
AB  - Improving public health requires multiple intervention strategies. Implementing
      such an intervention mix is supposed to require a multisectoral policy network.
      As evidence to support this assumption is scarce, we examined under which
      conditions public health-related policy networks were able to implement an
      intervention mix. Data were collected (2009-14) from 29 Dutch public health
      policy networks. Surveys were used to identify the number of policy sectors,
      participation of actors, level of trust, networking by the project leader, and
      intervention strategies implemented. Conditions sufficient for an intervention
      mix (>=3 of 4 non-educational strategies present) were determined in a fuzzy-set
      qualitative comparative analysis. A multisectoral policy network (>=7 of 14
      sectors present) was neither a necessary nor a sufficient condition. In
      multisectoral networks, additionally required was either the active participation
      of network actors (>=50% actively involved) or active networking by the project
      leader (>=monthly contacts with network actors). In policy networks that included
      few sectors, a high level of trust (positive perceptions of each other's
      intentions) was needed-in the absence though of any of the other conditions. If
      the network actors were also actively involved, an extra requirement was active
      networking by the project leader. We conclude that the multisectoral composition
      of policy networks can contribute to the implementation of a variety of
      intervention strategies, but not without additional efforts. However, policy
      networks that include only few sectors are also able to implement an intervention
      mix. Here, trust seems to be the most important condition.

PMID- 29040503
TI  - The role of early life growth development, the FTO gene and exclusive
      breastfeeding on child BMI trajectories.
AB  - Background: Recent studies have implicated the FTO gene in child and adult
      obesity. A longer duration of exclusive breastfeeding (EXBF) has been shown to
      reduce body mass index (BMI) and the risk of being overweight in the general
      population and among FTO gene carriers. However, it remains unclear whether the
      preventive effect of EXBF could be explained by its impact on early life growth
      development, e.g. ages at adiposity peak (AP) and adiposity rebound (AR) and BMI
      velocities in the first years of life, which are major determinants of overweight
      and obesity later in life. Methods: We studied 5590 children from the British
      Avon Longitudinal Study of Parents and Children (ALSPAC) cohort and modelled
      their longitudinal BMI profiles with mixed effects models from birth to 16 years
      of age, as well as their ages at AP, AR and BMI velocities in relation to the FTO
      gene variant and EXBF. Results: A longer duration of EXBF (i.e. at least 5
      months) has substantial impact on BMI growth trajectories among children carrying
      the FTO adverse variant by modulating the age at AP, age at AR and BMI
      velocities. EXBF acts antagonistically to the FTO rs9939609 risk allele and by
      the age of 15, the predicted reduction in BMI after 5 months of EXBF is 0.56
      kg/m2 [95% confidence interval (CI) 0.11-1.01; P = 0.003] and 1.14 kg/m2 (95% CI
      0.67-1.62; P < 0.0001) in boys and girls, respectively. Conclusions: EXBF
      influences early life growth development and thus plays a critical role in
      preventing the risks of overweight and obesity even when those are exacerbated by
      genetic factors.

PMID- 29040505
TI  - Late booking amongst African women in a London borough, England: implications for
      health promotion.
AB  - The National Institute for Health and Clinical Excellence guidance is that a
      pregnant woman should see a midwife within the first 13 weeks into her pregnancy,
      in what is known as the 'booking appointment' or the 'full assessment' where she
      discusses with the midwife her care plan, medical and family histories and social
      circumstances. Significant numbers of black African women present after 13 weeks
      into the pregnancy. This study explores why black African women access the
      booking appointment after 13 weeks of pregnancy in a London borough. The study
      took a qualitative approach and used semi-structured interviews with 23 women who
      self-identified as black African migrants born in a sub-Saharan African country,
      and had experience of using ante-natal services in the borough. Participants
      discussed how their cultural understandings of pregnancy influenced timing of the
      booking appointment. The data was analysed using the thematic approach. Cultural,
      economic and political contexts within which they experienced pregnancy
      influenced the timing. Whilst acknowledging the benefits of early booking, this
      was said to be at odds with their cultural beliefs where pregnancy disclosure
      within 13 weeks was considered inappropriate. Lack of information about the
      booking appointment and unresolved immigration issues led to perceptions that
      they were being brought under the Immigration Department's radar through the
      booking appointment. Whilst most health promotion information regarding the
      booking appointment is designed in a top-down fashion, health planners should
      also recognize ethnic diversities so as to market the booking appointment using
      downstream approaches that take account of the cultural, political and economic
      contexts in which migrants/ethnic minority populations live.

PMID- 29040506
TI  - High-throughput sequencing revealed novel Dehalococcoidia in dechlorinating
      microbial enrichments from PCB-contaminated marine sediments.
AB  - In this study, six PCE-to-ethene dechlorinating cultures, fed with a fermentable
      substrate (lactate) or hydrogen as electron donor, were obtained from PCB and PCE
      dechlorinating microcosms constructed with PCB-contaminated marine sediments. A
      novel Chloroflexi member (OTU-DIS1) affiliated to Dehalococcoidales Incertae
      Sedis, only distantly related to known dechlorinating bacteria, dominated the
      enrichment cultures (up to 86% of total OTUs). Sulfate-, thiosulfate- and sulfur
      reducing bacteria affiliated to genera Desulfobacter, Dethiosulfatibacter and
      Desulfuromusa were also found to lesser extent. Remarkably, tceA, vcrA and the
      bifunctional PCE/PCB dehalogenase genes pcbA1, pcbA4 and pcbA5 were found in all
      dechlorinating microbial enrichments indicating the coexistence of different
      Dehalococcoides mccartyi strains. The reductive dechlorination rate in each
      culture remained unvaried over long-term operation (~ 30 months) and ranged
      between 0.85 and 0.97 mmol Cl-1 released L-1 d-1 in the lactate-fed microbial
      enrichments and between 0.66 and 0.85 mmol Cl-1 released L-1 d-1 in the H2-fed
      microbial enrichments. Overall, this study highlights the presence of yet
      unexplored biodiversity in PCBs contaminated marine sediments and indicates these
      environments as promising sources of novel organohalide-respiring bacteria.

PMID- 29040507
TI  - Aortic valve replacement improves survival in severe aortic stenosis with
      gradient-area mismatch.
AB  - OBJECTIVES: To investigate whether and in which patients with catheter-derived
      low pressure gradient (PG, <40 mmHg) severe (aortic valve area <= 1 cm2) aortic
      stenosis and preserved left ventricular ejection fraction, early aortic valve
      replacement (AVR) might improve survival. METHODS: We investigated a total of 506
      consecutive patients (age 75 +/- 9 years, 58% men) with either moderate aortic
      stenosis (MAS) or severe aortic stenosis (SAS) and preserved left ventricular
      ejection fraction (>=50%) as defined at catheterization. Propensity score
      matching was used to select matched pairs of patients with and without AVR in
      each group. A 100% complete follow-up of all cause death was obtained after a
      median of 6.6 years (interquartile range 3.4-8.8 years). RESULTS: There were 62
      (12%) patients with MAS, 119 (24%) patients with SAS and low (<40 mmHg) PG and
      325 (64%) patients with SAS and high PG. Significantly less patients with MAS and
      low-gradient SAS underwent AVR compared to patients with high gradient SAS (58%
      vs 60% vs 83%, P < 0.001). In propensity score-matched patients, AVR was
      independently associated with a decrease in all-cause mortality in all groups (P
      < 0.05) regardless of the PG, stroke volume or aortic valve area. CONCLUSIONS:
      The present data indicate a that AVR improves survival in SAS regardless of the
      gradient and flow. This advocates an 'early-AVR' rather than a 'watchful waiting'
      strategy.

PMID- 29040508
TI  - Adult Lifetime Diet Quality and Physical Performance in Older Age: Findings From
      a British Birth Cohort.
AB  - Background: Current evidence that links "healthier" dietary patterns to better
      measured physical performance is mainly from older populations; little is known
      about the role of earlier diet. We examined adult diet quality in relation to
      physical performance at age 60-64 years. Methods: Diet quality was defined using
      principal component analysis of dietary data collected at age 36, 43, 53, and 60
      64. Throughout adulthood, diets of higher quality were characterized by higher
      consumption of fruit, vegetables, and wholegrain bread. Diet quality scores
      calculated at each age indicated compliance with this pattern. Physical
      performance was assessed using chair rise, timed-up-and-go, and standing balance
      tests at age 60-64. The analysis sample included 969 men and women. Results: In
      gender-adjusted analyses, higher diet quality at each age was associated with
      better measured physical performance (all p < .01 for each test), although some
      associations were attenuated after adjustment for covariates. Diet quality scores
      were highly correlated in adulthood (0.44 <= r <= 0.67). However, conditional
      models showed that higher diet quality at age 60-64 (than expected from scores at
      younger ages), was associated with faster chair rise speed and with longer
      standing balance time (adjusted: 0.08 [95% CI: 0.02, 0.15] and 0.07 [0.01, 0.14]
      SD increase in chair rise speed and balance time, respectively, per SD increase
      in conditional diet quality; both p < .05). Conclusions: Higher diet quality
      across adulthood is associated with better physical performance in older age.
      Current diet quality may be particularly important for physical performance,
      suggesting potential for improvements in diet in early older age.

PMID- 29040509
TI  - A new use for an old tool: maternity waiting homes to improve equity in rural
      childbirth care. Results from a cross-sectional hospital and community survey in
      Tanzania.
AB  - Limited quality of childbirth care in sub-Saharan Africa primarily affects the
      poor. Greater quality is available in facilities providing advanced management of
      childbirth complications. We aimed to determine whether Maternity Waiting Homes
      (MWHs) may be a tool to improve access of lower socio-economic women to such
      facilities. Secondary analysis of a cross-sectional hospital survey from Iringa
      District, Tanzania was carried out. Women who delivered between October 2011 and
      May 2012 in the only District facility providing comprehensive Emergency
      Obstetric Care were interviewed. Their socio-economic profile was obtained by
      comparison with District representative data. Multivariable logistic regression
      was used to compare women who had stayed in the MWH before delivery with those
      who had accessed the hospital directly. Out of 1072 study participants, 31.3% had
      accessed the MWH. In multivariable analysis, age, education, marital status and
      obstetric factors were not significantly associated with MWH stay. Adjusted odds
      ratios for MWH stay increased progressively with distance from the hospital
      (women living 6-25 km, OR 4.38; 26-50 km, OR 4.90; >50 km, OR 5.12). In adjusted
      analysis, poorer women were more likely to access the MWH before hospital
      delivery compared with the wealthiest quintile (OR 1.38). Policy makers should
      consider MWH as a tool to mitigate inequity in rural childbirth care.

PMID- 29040510
TI  - Genomic fragmentation and extrachromosomal telomeric repeats impact assessment of
      telomere length in human spermatozoa: quantitative experiments and systematic
      review.
AB  - STUDY QUESTION: Can differences in DNA isolation alter assessment of sperm
      telomere length (spTL) and do they account for conflicting results in the
      literature on spTL and male fertility? SUMMARY ANSWER: DNA isolation methods
      preferentially include or exclude short, extrachromosomal (EC) telomere-specific
      sequences that alter spTL measurements, and are responsible for a proportion of
      the disparity observed between investigations. WHAT IS KNOWN ALREADY: The
      relationship between spTL and male fertility has become an active area of
      research. The results across investigations, however, have been discordant,
      generating a need to critically evaluate the existing body of knowledge to guide
      future investigations. STUDY DESIGN, SIZE, DURATION: Quantitative experiments
      determined the effect of DNA isolation on the integrity of sperm DNA and measures
      of spTL, while a systematic analysis of the current literature evaluated the
      effect of DNA isolation and study design on experimental outcomes.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Two DNA isolation methods were
      compared: Genomic Tips which isolate 'High Molecular Weight' (HMW) DNA
      exclusively, and QIAamp(r) DNA Mini which isolates 'Total' genomic DNA
      irrespective of size. DNA quality was assessed via field inversion gel
      electrophoresis (FIGE) and spTL was measured via terminal restriction fragment
      analysis. In addition, major databases in medicine, health and the life sciences
      were subject to a targeted search, and results were independently screened
      according to defined exclusion/inclusion criterion. Findings from primary
      articles were analyzed for concordance and study designs were compared across six
      moderator variables (sample size, participant age, fertility status, semen
      fraction, telomere population and type of analysis). MAIN RESULTS AND THE ROLE OF
      CHANCE: HMW DNA spTL was significantly longer than spTL measured from total DNA
      (P < 0.01), indicating that Total DNA contained short, EC telomeric repeats that
      shifted downstream assessment towards shorter spTL. HMW DNA spTL reflected the
      length of intact, chromosomal telomeres. Major findings on spTL showed the
      greatest concordance amongst studies that implemented HMW DNA isolation prior to
      spTL assessment. Studies that utilized Total DNA varied in concordance, but
      outcomes were similar if (i) a comparative analysis was applied or (ii) a sample
      size threshold of 81 was achieved for correlative analysis. LIMITATIONS, REASONS
      FOR CAUTION: Chromosomal and EC telomeric DNA were distinguished based on
      outcomes of HMW DNA isolation and size. Further experiments are required to
      determine the nature and function of these two types of telomeric sequences.
      WIDER IMPLICATIONS OF THE FINDINGS: This study reveals a dramatic impact of
      upstream DNA processing and study design on measurements of spTL, which accounts
      for conflicting results in the literature. Future assessments of spTL should
      incorporate independent detection of chromosomal and EC telomeric DNA and
      specific experimental planning. STUDY FUNDING/COMPETING INTERESTS: This study was
      funded by CReATe Fertility Centre, Toronto, Ontario, Canada. The authors have
      declared no conflict of interest. REGISTRATION NUMBER: N/A.

PMID- 29040511
TI  - Development of the testis in pre-pubertal boys with cancer after biopsy for
      fertility preservation.
AB  - STUDY QUESTION: Is testicular growth affected by a testicular biopsy intended for
      fertility preservation in pre-pubertal boys with cancer? SUMMARY ANSWER:
      Testicular growth of the biopsied testis is not impeded in comparison to the non
      biopsied contralateral testis up until 1 year after surgery. WHAT IS KNOWN
      ALREADY: Fertility preservation in pre-pubertal boys by means of testicular
      biopsy has been conducted for more than 15 years. Although immediate adverse
      effects of testicular biopsy are rare (1%), no data exist on the effect of biopsy
      on testicular growth. STUDY DESIGN, SIZE, DURATION: In this prospective cohort
      study, between March 2011 and February 2017, 93 parents of pre-pubertal boys were
      offered cryopreservation of testicular tissue of their son, of whom 78 consented.
      Sixty-four boys were included in this follow-up study. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: All boys with cancer at the paediatric oncology department of
      the Academic Medical Center (AMC) who needed gonadotoxic therapy and were unable
      to ejaculate were offered cryopreservation of testicular tissue prior to
      treatment. By testicular ultrasound before and after biopsy (1, 6 and 12 months
      after biopsy), volume and parenchymal abnormalities were assessed. Data were
      analysed using mixed-effects modelling. MAIN RESULTS AND THE ROLE OF CHANCE: Of
      the 64 included boys all were followed up at 1 month, 58 at 6 months and 55 at 12
      months. Mean testicular volumes after 1, 6 and 12 months after biopsy were 1.7 +/
      2.1, 1.7 +/- 2.2 and 1.9 +/- 2.4 for the biopsied testis and 1.8 +/- 2.2, 1.8 +/
      2.3 and 2.0 +/- 2.2 for the non-biopsied testis, respectively. Biopsy of the
      testis did not have a significant impact on testicular growth. Immediate adverse
      effects of the biopsy, i.e. wound infections, were seen in 3/78 boys (3.8%).
      LIMITATIONS, REASONS FOR CAUTION: Although it is the largest cohort available to
      date, the number of patients included in our follow-up is still relatively small.
      A larger cohort would be able to evaluate growth more precisely. Follow-up was
      discontinued in a significant portion of boys, 12/76 (15.8%), mainly because of
      death due to primary illness but also because they could not be reached or
      declined further follow-up. WIDER IMPLICATIONS OF THE FINDINGS: These reassuring
      data may be used in counselling future boys who are eligible for fertility
      preservation and their parents. STUDY FUNDING/COMPETING INTEREST(S): Study funded
      by KIKA Foundation (Kika 86), Grant from the Netherlands Organisation for Health
      Research and Development (ZonMW TAS-116003002). The authors declare no conflict
      of interest. TRIAL REGISTRATION NUMBER: CCMO-register: NL27690.000.09.

PMID- 29040512
TI  - Fertility-related knowledge and reproductive goals in childhood cancer survivors:
      short communication.
AB  - STUDY QUESTION: Do young adult survivors of childhood cancer know their fertility
      status, in the context of their parenthood goals and screening for gonadal
      functioning? SUMMARY ANSWER: While 80% of survivors (who were without children)
      wanted children in the future, most did not know their fertility status, and
      screening for gonadal functioning was underutilized. WHAT IS KNOWN ALREADY:
      Survivors of childhood cancer are at risk for infertility, but fertility
      counseling and assessment are underutilized. Separate studies indicated that
      survivors' fertility-related knowledge is poor and that they often wanted to have
      children. Yet, studies have not investigated the intersection of both issues, as
      well as potential distress if parenthood goals are not met. STUDY DESIGN, SIZE,
      DURATION: Young adult male and female survivors of childhood cancer (N = 149)
      completed cross-sectional surveys, and data for those without children (n = 105,
      70.5%) are presented here. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants
      were 20-40 years old (M = 26.5), diagnosed 5-33 years prior to study
      participation, and completed questionnaires online. Knowledge of fertility
      status, parenthood goals, and potential distress if survivors were unable to have
      children were assessed. Medical records were reviewed for hormone levels as
      indicators of screening for gonadal functioning. MAIN RESULTS AND THE ROLE OF
      CHANCE: Most survivors (n = 81; 77.1%) did not know their fertility status, while
      over 80% (n = 89) wanted children (neither aspect varied by socio
      demographic/cancer-specific factors). Two-thirds of survivors indicated they
      would be distressed if parenthood goals remained unfulfilled; especially female
      (versus male, t = 2.64; P = 0.01) or partnered (versus single, t = -3.45; P <
      0.001) survivors. Forty survivors (38.1%) had documented assessments of gonadal
      functioning, of which 33 (82.5%) reported not knowing their fertility status.
      LIMITATIONS, REASONS FOR CAUTION: Relevant risk factors may have not been
      identified owing to limited sample size and missing treatment information. The
      underutilization of screening for gonadal functioning needs further exploration
      in other pediatric centers. WIDER IMPLICATIONS OF THE FINDINGS: Most adult
      childhood cancer survivors want to become parents, but do not know their
      fertility status, which could cause significant psychological distress.
      Healthcare providers should continuously address fertility among survivors, but
      more research is needed on how to implement routine fertility counseling and/or
      testing. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the
      Research Institute at Nationwide Children's Hospital (V.L.) and Dutch Cancer
      Society (RUG2009-4442, M.A.T.). All authors have no conflict of interest to
      declare.

PMID- 29040514
TI  - Commentary: Fisher 1918: the foundation of the genetics and analysis of complex
      traits.

PMID- 29040513
TI  - Targeted metabolomics reveals reduced levels of polyunsaturated choline
      plasmalogens and a smaller dimethylarginine/arginine ratio in the follicular
      fluid of patients with a diminished ovarian reserve.
AB  - STUDY QUESTION: Does the metabolomic profile of the follicular fluid (FF) of
      patients with a diminished ovarian reserve (DOR) differ from that of patients
      with a normal ovarian reserve (NOR)? SUMMARY ANSWER: The metabolomic signature of
      the FF reveals a significant decrease in polyunsaturated choline plasmalogens and
      methyl arginine transferase activity in DOR patients compared to NOR patients.
      WHAT IS KNOWN ALREADY: The composition of the FF reflects the exchanges between
      the oocyte and its microenvironment during its acquisition of gametic competence.
      Studies of the FF have allowed identification of biomarkers and metabolic
      pathways involved in various pathologies affecting oocyte quality, but no large
      metabolomic analysis in the context of ovarian ageing and DOR has been undertaken
      so far. STUDY DESIGN, SIZE, DURATION: This was an observational study of the FF
      retrieved from 57 women undergoing in vitro fertilization at the University
      Hospital of Angers, France, from November 2015 to September 2016. The women were
      classified in two groups: one including 28 DOR patients, and the other including
      29 NOR patients, serving as controls. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Patients were enrolled in the morning of oocyte retrieval after ovarian
      stimulation. Once the oocytes were isolated for fertilization and culture, the FF
      was pooled and centrifuged for analysis. A targeted quantitative metabolomic
      analysis was performed using high-performance liquid chromatography coupled with
      tandem mass spectrometry, and the Biocrates Absolute IDQ p180 kit. The FF levels
      of 188 metabolites and several sums and ratios of metabolic significance were
      assessed by multivariate and univariate analyses. MAIN RESULTS AND THE ROLE OF
      CHANCE: A total of 136 metabolites were accurately quantified and used for
      calculating 23 sums and ratios. Samples were randomly divided into training and
      validation sets. The training set, allowed the construction of multivariate
      statistical models with a projection-supervised method, i.e. orthogonal partial
      least squares discriminant analysis (OPLS-DA), applied to the full set of
      metabolites, or the penalized least absolute shrinkage and selection operator
      with logistic regression (LASSO-LR), applied to the ratios and sums of the
      metabolites. Both multivariate models showed good predictive performances when
      applied to the validation set. The final penalized model retained the three most
      significant variables, i.e. the total dimethylarginine-to-arginine ratio (Total
      DMA/Arginine), the sum of the polyunsaturated choline plasmalogens (PUFA ae), and
      the patient's age. The negative coefficients of Total DMA/Arginine and PUFA ae
      indicated that these FF variables had lower values in DOR patients than in NOR
      patients. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: This study
      presents two limitations. First, with this targeted metabolomics analysis, we
      have explored only a limited portion of the FF metabolome. Second, although the
      signature found was highly significant, the mechanism underlying the dysfunction
      remains undetermined. WIDER IMPLICATIONS OF THE FINDINGS: The understanding of
      the mechanisms implied in ovarian ageing is essential for providing an adequate
      response to affected women desiring pregnancy. Our study proposes an incoming
      signature that may open new paths towards this goal. STUDY FUNDING/COMPETING
      INTEREST(S): This study was supported by the University Hospital of Angers, the
      University of Angers, and the French national research centers, INSERM and the
      CNRS. There were no competing interests.

PMID- 29040517
TI  - Filamin A mitral valve disease: prolapse, dystrophy, or dysplasia?

PMID- 29040515
TI  - Resilience and recovery of Dehalococcoides mccartyi following low pH exposure.
AB  - Bioremediation treatment (e.g. biostimulation) can decrease groundwater pH with
      consequences for Dehalococcoides mccartyi (Dhc) reductive dechlorination
      activity. To explore the pH resilience of Dhc, the Dhc-containing consortium BDI
      was exposed to pH 5.5 for up to 40 days. Following 8- and 16-day exposure periods
      to pH 5.5, dechlorination activity and growth recovered when returned to pH 7.2;
      however, the ability of the culture to dechlorinate vinyl chloride (VC) to ethene
      was impaired (i.e. decreased rate of VC transformation). Dhc cells exposed to pH
      5.5 for 40 days did not recover the ethene-producing phenotype upon transfer to
      pH 7.2 even after 200 days of incubation. When returned to pH 7.2 conditions
      after an 8-, a 16- and a 40-day low pH exposure, tceA and vcrA genes showed
      distinct fold increases, suggesting Dhc strain-specific responses to low pH
      exposure. Furthermore, a survey of Dhc biomarker genes in groundwater samples
      revealed the average abundances of Dhc 16S rRNA, tceA and vcrA genes in pH 4.5-6
      groundwater were significantly lower (P-value < 0.05) than in pH 6-8.3
      groundwater. Overall, the results of the laboratory study and the assessment of
      field data demonstrate that sustained Dhc activity should not be expected in low
      pH groundwater, and the duration of low pH exposure affects the ability of Dhc to
      recover activity at circumneutral pH.

PMID- 29040516
TI  - Integrated mental health services in China: challenges and planning for the
      future.
AB  - Eager to build an integrated community-based mental health system, in 2004 China
      started the '686 Programme', whose purpose was to integrate hospital and
      community services for patients with serious mental illness. In 2015, the
      National Mental Health Working Plan (2015-2020) proposed an ambitious strategy
      for implementing this project. The goal of this review is to assess potential
      opportunities for and barriers to successful implementation of a community-based
      mental health system that integrates hospital and community mental health
      services into the general healthcare system. We examine 7066 sources in both
      English and Chinese: the academic peer-reviewed literature, the grey literature
      on mental health policies, and documents from government and policymaking
      agencies. Although China has proposed a number of innovative programmes to
      address its mental health burden, several of these proposals have yet to be fully
      activated, particularly those that focus on integrated care. Integrating mental
      health services into China's general healthcare system holds great promise for
      increased access to and quality improvement in mental health services, as well as
      decreased stigma and more effective management of physical and mental health
      comorbidities. This article examines the challenges to integrating mental health
      services into China's general healthcare system, especially in the primary care
      sphere, including: accurately estimating mental health needs, integrating mental
      and physical healthcare, increasing workforce development and training, resolving
      interprofessional issues, financing and funding, developing an affordable and
      sustainable mental health system, and delivering care to specific subpopulations
      to meet the needs of China's diverse populace. As China's political commitment to
      expanding its mental health system is rapidly evolving, we offer suggestions for
      future directions in addressing China's mental health needs.

PMID- 29040518
TI  - Challenges in comparing the non-vitamin K antagonist oral anticoagulants for
      atrial fibrillation-related stroke prevention.
AB  - The aim of this review is to provide context for meta-analyses interpreting data
      from phase III stroke prevention studies of non-vitamin K antagonist oral
      anticoagulants (NOACs) in patients with non-valvular atrial fibrillation (NVAF).
      Differences between the four phase III NOAC stroke prevention studies in patients
      with NVAF (ROCKET AF, ARISTOTLE, RE-LY, and ENGAGE AF), their potential impact on
      outcomes, and inter-study differences were evaluated, as well as the potential
      role of real-world evidence in evaluating NOACs in this setting. Study design
      differences included blinding strategy, dose-reduction options, and transition
      from blinded treatment to standard of care. There were small but relevant
      variations in the definition of AF used (RE-LY used the least precise
      definition); patient risk profiles (ROCKET AF patients had the highest risk); the
      primary safety outcome (a composite of major bleeding and clinically relevant non
      major bleeding events in ROCKET AF vs. major bleeding in the others); and the
      definitions of stroke, major bleeding, and clinically relevant non-major bleeding
      events. In real-world studies, methodological variations and biases are
      amplified, making cross-study comparisons and meta-analyses problematic. Because
      of these methodological differences, meta-analyses of phase III studies need to
      be robust, and if outcomes of the reference (warfarin-treated) arms differ
      significantly, the basis of the meta-analysis is not strong. These key issues
      need to be taken into consideration for direct comparisons across studies, and
      for the interpretation of meta-analytic data.

PMID- 29040519
TI  - High gonadotropin dosage does not affect euploidy and pregnancy rates in IVF PGS
      cycles with single embryo transfer.
AB  - STUDY QUESTION: Does high gonadotropin dosage affect euploidy and pregnancy rates
      in PGS cycles with single embryo transfer? SUMMARY ANSWER: High gonadotropin
      dosage does NOT affect euploidy and pregnancy rates in PGS cycles with single
      embryo transfer. WHAT IS KNOWN ALREADY: PGS has been proven to be the most
      effective and reliable method for embryo selection in IVF cycles. Euploidy and
      blastulation rates decrease significantly with advancing maternal age. In order
      to recruit an adequate number of follicles, the average dosage of gonadotropins
      administered during controlled ovarian stimulation in IVF cycles often increases
      significantly with advancing maternal age. STUDY DESIGN, SIZE, AND DURATION: A
      retrospective study of SNP (Single Nucleotide Polymorphism) PGS outcome data from
      blastocysts biopsied on day 5 or day 6 was conducted to identify differences in
      euploidy and clinical pregnancy rates. Seven hundred and ninety four cycles of
      IVF treatment with PGS between January 2013 and January 2017 followed by 651
      frozen embryo transfers were included in the study (506 patients, maternal age
      (y.o.) - 37.2 +/- 4.31). PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of
      4034 embryos were analyzed (5.1 +/- 3.76 per case) for euploidy status. All
      embryos were vitrified after biopsy, and selected embryos were subsequently
      thawed for a hormone replacement frozen embryo transfer cycle. All cycles were
      analyzed by total gonadotropin dosage (<3000 IU, 3000-5000 IU and >5000 IU), by
      number of eggs retrieved (1-5, 5-10, 10-15 and >15 eggs) and patient's age (<35,
      35-37, 38-40 and >=41 y.o.). Clinical pregnancy rate was defined by the presence
      of a fetal heartbeat at 6-7 weeks of gestation. MAIN RESULTS AND THE ROLE OF
      CHANCE: Euploidy rates within the same age group were not statistically different
      regardless of the total dosage of gonadotropins used or the number of eggs
      retrieved. In the youngest group of patients (<35 y.o. - 187 IVF cycles) euploidy
      rates ranged from 62.3% (<3000 IU were used in the IVF cycle) to 67.5% (>5000 IU
      were used in the IVF cycle) (OR = 0.862, 95% CI 0.687-1.082, P = 0.2) and from
      69.5% (1-5 eggs retrieved) to 60.0% (>15 eggs retrieved) (OR = 0.658, 95% CI
      0.405-1.071, P = 0.09). Similar data were obtained in the oldest group of
      patients (>=41 y.o. - 189 IVF cycles): euploidy rates ranged from 30.7 to 26.4%
      (OR = 0.811, 95% CI 0.452-1.454, P = 0.481) when analyzed by total dosage of
      gonadotropins used in the IVF cycle and from 40.0 to 30.7% (OR = 0.531, 95% CI
      0.204-1.384, P = 0.19), when assessed by the total number of eggs retrieved.
      Ongoing pregnancy rates were similar, not only within particular age groups, but
      also between different age groups regardless of the total dosage of gonadotropins
      used: ranging from to 63.6% (<3000 IU, < 35 y.o.) to 54.8% (>5000 IU, >=41 y.o)
      (OR = 0.696, 95% CI 0.310-1.565, P = 0.38). LIMITATIONS, REASONS FOR CAUTION:
      Retrospective study and heterogeneity of patients included. WIDER IMPLICATIONS OF
      THE FINDINGS: These data are reassuring for the common practice of increasing
      gonadotropin dosages in PGS cycles, particularly in older woman. STUDY
      FUNDING/COMPETING INTEREST(S): No formal funding has been received for this
      study. TRIAL REGISTRATION NUMBER: N/A.

PMID- 29040520
TI  - Clinical implications of mitochondrial DNA quantification on pregnancy outcomes:
      a blinded prospective non-selection study.
AB  - STUDY QUESTION: Can quantification of mitochondrial DNA (mtDNA) in trophectoderm
      (TE) biopsy samples provide information concerning the viability of a blastocyst,
      potentially enhancing embryo selection and improving IVF treatment outcomes?
      SUMMARY ANSWER: This study demonstrated that euploid blastocysts of good
      morphology, but with high mtDNA levels had a greatly reduced implantation
      potential. WHAT IS KNOWN ALREADY: Better methods of embryo selection leading to
      IVF outcome improvement are necessary, as the transfer of chromosomally normal
      embryos of high morphological grade cannot guarantee the establishment of an
      ongoing pregnancy. The quantity of mtDNA in embryonic cells has been proposed as
      a new biomarker of viability-higher levels of mtDNA associated with reduced
      implantation potential. STUDY DESIGN, SIZE, DURATION: mtDNA was quantified in 199
      blastocysts, previously biopsied and shown to be chromosomally normal using
      preimplantation genetic testing for aneuploidy (PGT-A). These were generated by
      174 couples (average female age 37.06 years). All patients underwent IVF in a
      single clinic. The study took place in a blinded, non-selection manner-i.e. mtDNA
      quantity was not known at the time of single embryo transfer. The fate of the
      embryos transferred was subsequently compared to the mtDNA levels measured.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Embryos were biopsied at the blastocyst
      stage. The TE samples obtained were subjected to whole genome amplification
      followed by comprehensive chromosome analysis via next generation sequencing. The
      same biopsy specimens were also tested using quantitative PCR, allowing highly
      accurate mtDNA quantification. After blastocyst transfer, the code used for
      blinding was broken and analysis undertaken to reveal whether the amount of mtDNA
      had any association with embryo implantation. MAIN RESULTS AND THE ROLE OF
      CHANCE: mtDNA analysis of the 199 blastocysts revealed that 9 (5%) contained
      unusually high levels of mtDNA. All embryo transfers involved a single
      chromosomally normal blastocyst of good morphology. Of these, 121 (60%) led to
      ongoing pregnancies, 11(6%) led to biochemical pregnancies, and 10 (5%)
      spontaneously miscarried. All (100%) of these blastocysts had mtDNA levels
      considered to be normal/low. The remaining 57 (29%) blastocysts failed to
      implant. Among these non-viable embryos there were 9 (16%) with unusually high
      levels of mtDNA. This meant that the ongoing pregnancy rate for morphologically
      good, euploid blastocysts, with normal/low levels of mtDNA was 64% (121/190). In
      contrast, the ongoing pregnancy rate for the same type of embryos, but with
      elevated mtDNA levels, was 0/9 (0%). This difference was highly statistically
      significant (P < 0.0001). LIMITATIONS REASONS FOR CAUTION: To determine the true
      extent of any clinical benefits a randomized clinical trial will be necessary.
      Research is needed to improve understanding of the biology of mtDNA expansion.
      WIDER IMPLICATIONS OF THE FINDINGS: This is the first investigation to evaluate
      the clinical impact of increased mtDNA in a prospective blinded manner. Results
      confirm that embryos with elevated mtDNA rarely implant, supporting its use as a
      viability biomarker. A total of 64% of euploid blastocysts with normal/low mtDNA
      implanted versus 60% for the cohort as a whole. STUDY FUNDING/COMPETING
      INTEREST(S): This study was supported by institutional funding (Reprogenetics UK
      and Reprogenetics). DW is supported by the National Institute for Health Research
      (NIHR) Oxford Biomedical Research Centre Programme. None of the authors have any
      competing interests.

PMID- 29040521
TI  - Is the rapidly paced pig the optimal model for endocardial cardiac
      resynchronization therapy?

PMID- 29040523
TI  - Is the rapidly paced pig the optimal model for endocardial cardiac
      resynchronization therapy?-Authors' reply.

PMID- 29040522
TI  - Behavioral and transcriptomic analysis of Trem2-null mice: not all knockout mice
      are created equal.
AB  - It is clear that innate immune system status is altered in numerous
      neurodegenerative diseases. Human genetic studies have demonstrated that
      triggering receptor expressed in myeloid cells 2 (TREM2) coding variants have a
      strong association with Alzheimer's disease (AD) and other neurodegenerative
      diseases. To more thoroughly understand the impact of TREM2 in vivo, we studied
      the behavioral and cognitive functions of wild-type (WT) and Trem2-/- (KO) mice
      during basal conditions and brain function in the context of innate immune
      stimulation with peripherally administered lipopolysaccharide (LPS). Early
      markers of neuroinflammation preceded Aif1 and Trem2 upregulation that occurred
      at later stages (24-48 h post-LPS). We performed a transcriptomic study of these
      cohorts and found numerous transcripts and pathways that were altered in Trem2-/-
      mice both at baseline and 48 h after LPS challenge. Importantly, our
      transcriptome analysis revealed that our Trem2-/- mouse line (Velocigene allele)
      results in exaggerated Treml1 upregulation. In contrast, aberrantly high Treml1
      expression was absent in the Trem2 knockout line generated by the Colonna lab and
      the Jackson Labs CRISPR/Cas9 Trem2 knockout line. Notably, removal of the floxed
      neomycin selection cassette ameliorated aberrant Treml1 expression, validating
      the artifactual nature of Treml1 expression in the original Trem2-/- Velocigene
      line. Clearly further studies are needed to decipher whether the Treml1
      transcriptional artifact is functionally meaningful, but our data indicate that
      caution is warranted when interpreting functional studies with this particular
      line. Additionally, our results indicate that other Velocigene alleles or
      targeting strategies with strong heterologous promoters need to carefully
      consider downstream genes.

PMID- 29040524
TI  - Potentiation of excitatory synaptic transmission ameliorates aggression in mice
      with Stxbp1 haploinsufficiency.
AB  - Genetic studies point to a major role of de novo mutations in neurodevelopmental
      disorders of intellectual disability, autism spectrum disorders, and epileptic
      encephalopathy. The STXBP1 gene encodes the syntaxin-binding protein 1 (Munc18-1)
      that critically controls synaptic vesicle exocytosis and synaptic transmission.
      This gene harbors a high frequency of de novo mutations, which may play roles in
      these neurodevelopmental disorders. However, the system and behavioral-level
      pathophysiological changes caused by these genetic defects remain poorly
      understood. Constitutional (Stxbp1+/-), dorsal-telencephalic excitatory
      (Stxbp1fl/+/Emx), or global inhibitory neuron-specific (Stxbp1fl/+/Vgat) mice
      were subjected to a behavioral test battery examining locomotor activity,
      anxiety, fear learning, and social interactions including aggression.
      Furthermore, measurements of local field potentials in multiple regions of the
      brain were performed. Stxbp1+/- male mice exhibited enhanced aggressiveness and
      impaired fear learning associated with elevated gamma activity in several regions
      of the brain including the prefrontal cortex. Stxbp1fl/+/Emx mice showed fear
      learning deficits, but neither Stxbp1fl/+/Emx nor Stxbp1fl/+/Vgat mice showed
      increased aggressiveness. Pharmacological potentiation of the excitatory
      transmission at active synapses via the systemic administration of ampakine
      CX516, which enhances the excitatory postsynaptic function, ameliorated the
      aggressive phenotype of Stxbp1+/- mice. These findings suggest that synaptic
      impairments of the dorsal telencephalic and subcortical excitatory neurons cause
      learning deficits and enhanced aggression in Stxbp1+/- mice, respectively.
      Additionally, normalizing the excitatory synaptic transmission is a potential
      therapeutic option for managing aggressiveness in patients with STXBP1 mutations.

PMID- 29040525
TI  - Beta-blockers for heart failure with reduced, mid-range, and preserved ejection
      fraction: an individual patient-level analysis of double-blind randomized trials.
AB  - Aims: Recent guidelines recommend that patients with heart failure and left
      ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF >=
      50%. We investigated the effect of beta-blockers according to LVEF in double
      blind, randomized, placebo-controlled trials. Methods and results: Individual
      patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart
      rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary
      outcomes were all-cause mortality and cardiovascular death over 1.3 years median
      follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus
      rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients
      with LVEF 40-49% and 244 >= 50%. Beta-blockers reduced all-cause and
      cardiovascular mortality compared to placebo in sinus rhythm, an effect that was
      consistent across LVEF strata, except for those in the small subgroup with LVEF
      >= 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta
      blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59
      [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292
      [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95%
      CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601),
      LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF
      >=50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers
      increased LVEF when < 50% at baseline, but did not improve prognosis. Conclusion:
      Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus
      rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar
      benefit was observed in the subgroup of patients with LVEF 40-49%.

PMID- 29040526
TI  - Phenology of the Potato Psyllid, Bactericera cockerelli (Hemiptera: Triozidae),
      and "Candidatus Liberibacter solanacearum" in Commercial Potato Fields in Idaho.
AB  - Zebra chip disease (ZC) is an emerging disease of potato in which tubers are
      produced with striped necrotic patterns that make them unmarketable. ZC is
      associated with the bacterium "Candidatus Liberibacter solanacearum" (Lso), which
      is transmitted by the potato psyllid, Bactericera cockerelli (Sulc; Hemiptera:
      Triozidae). First found in Idaho during 2011, ZC now contributes to increased
      production costs each season via additional insecticide sprays. To clarify the
      extent and severity of the threat of ZC in Idaho, we sampled potato psyllids in
      commercial potato fields across the state over four growing seasons (2012-2015).
      All life stages of psyllids were sampled using a combination of methods (yellow
      sticky traps, vacuum samples, and leaf samples), and adult psyllids were tested
      for the presence of Lso by Polymerase Chain Reaction (PCR). Abundance of potato
      psyllids initially increased gradually over each growing season, then exhibited a
      sharp late-season rise and a sharp decline as most fields were being harvested.
      Abundance of psyllids was higher at warmer, lower elevation sites, but
      infestation onset did not differ between growing regions. Fewer psyllids were
      collected in vacuum samples than in sticky trap samples. Nymphs and eggs were
      found only late season and during years with high abundance of adults. Overall
      incidence of Lso was similar among all years but one. The results presented here
      clarify our understanding of the seasonal phenology of potato psyllids and Lso in
      Idaho potato fields and will aid in developing integrated management strategies
      against this important pest of potato.

PMID- 29040528
TI  - Improving Cardiovascular Risk Prediction: A Tale of Sisyphus.

PMID- 29040527
TI  - In- and Out-of-hospital Mortality Associated with Seasonal and Pandemic Influenza
      and Respiratory Syncytial Virus in South Africa, 2009-2013.
AB  - Background: Estimates of influenza- and respiratory syncytial virus (RSV)
      associated mortality burden are important to guide policy for control. Data are
      limited on the contribution of out-of-hospital deaths to this mortality. Methods:
      We modeled excess mortality attributable to influenza and RSV infection by
      applying regression models to weekly deaths from national vital statistics from
      2009 through 2013, using influenza and RSV laboratory surveillance data as
      covariates. We fitted separate models for in- and out-of-hospital deaths.
      Results: There were 509791 average annual deaths in South Africa, of which 44%
      (95% confidence interval [CI] 43%-45%) occurred out-of-hospital. Seasonal
      influenza and RSV all-cause mortality rates were 23.0 (95% CI 11.0-30.6) and 13.2
      (95% CI 6.4-33.8) per 100000 population annually (2.3% [95%CI 2.3%-2.4%] and 1.3%
      [95% CI 1.2%-1.4%] of all deaths respectively). The peak mortality rate was in
      individuals aged >=75 years (386.0; 95% CI 176.5-466.3) for influenza and in
      infants (143.4; 95% CI 0-194.8) for RSV. Overall, 63% (95% CI 62%--65%) of
      seasonal influenza and 48% (95% CI 47%-49%) of RSV-associated deaths occurred out
      of-hospital. Among children aged <5 years, RSV-associated deaths were more likely
      to occur in-hospital, whereas influenza-associated deaths were more likely to
      occur out-of-hospital. The mortality rate was 6.7 (95% CI 6.4-33.8) in the first
      influenza A(H1N1)pdm09 wave in 2009 and 20.9 (95% CI 6.4-33.8) in the second wave
      in 2011, with 30% (95% CI 29%-32%) of A(H1N1)pdm09-associated deaths in 2009
      occurring out-of-hospital. Discussion: More than 45% of seasonal influenza- and
      RSV-associated deaths occur out-of-hospital in South Africa. These data suggest
      that hospital-based studies may substantially underestimate mortality burden.

PMID- 29040529
TI  - Insulin resistance in a large cohort of women with polycystic ovary syndrome: a
      comparison between euglycaemic-hyperinsulinaemic clamp and surrogate indexes.
AB  - STUDY QUESTION: Could surrogate indexes identify insulin resistant individuals
      among women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Surrogate
      indexes may be able to rule in, but not rule out, insulin resistance in women
      with PCOS. WHAT IS KNOWN ALREADY: Insulin resistance is a typical finding of
      women with PCOS and most clinical information on this issue is based upon
      surrogate indexes of insulin resistance. However, data on the performance of
      these indexes in PCOS women are very limited. STUDY DESIGN SIZE, DURATION: A
      retrospective analysis of 406 women referred to our outpatient clinic for
      hyperandrogenism and/or menstrual dysfunction and submitted to hyperinsulinemic
      euglycaemic clamp between 1998 and 2015. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: In total, 375 of these women had PCOS by the Rotterdam criteria and were
      included in the study. Six surrogate indexes of insulin sensitivity were
      calculated from glucose and insulin levels, either at fasting (homeostasis model
      assessment (HOMA), glucose/insulin (G/I) ratio and quantitative insulin
      sensitivity check index (QUICKI)) or after oral glucose load (Gutt, Stumvoll0-120
      and Matsuda). MAIN RESULTS AND THE ROLE OF CHANCE: Overall, insulin resistance,
      as identified by the M-clamp value, was found in 74.9% of these women. The
      percentage was 59.3% in normal-weight vs 77.5% in overweight and 93.9% in obese
      subjects. All surrogate indexes were highly correlated with the M-clamp values.
      However, their ability to identify insulin resistant individuals was limited, in
      terms of sensitivity and especially in normal-weight subjects. ROC analysis
      showed similar performances of these indexes (AUC values 0.782-0.817).
      LIMITATIONS REASONS FOR CAUTION: Potential referral bias of PCOS patients may
      have caused overestimation of the prevalence of insulin resistance in these
      women. WIDER IMPLICATIONS OF THE FINDINGS: By using surrogate indexes many
      subjects with PCOS may be erroneously diagnosed as insulin sensitive, especially
      among normal-weight women. These indexes can be used to rule in, but not rule
      out, insulin resistance in PCOS. STUDY FUNDING/COMPETING INTEREST(S): Academic
      grants to P. Moghetti from the University of Verona. All authors declare no
      conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

PMID- 29040530
TI  - The prevalence of Type 2 diabetes is not increased in normal-weight women with
      PCOS.
AB  - STUDY QUESTION: Is oral glucose tolerance test (OGTT) needed in all women with
      polycystic ovary syndrome (PCOS)? SUMMARY QNSWER: OGTT is not routinely needed in
      women with PCOS and BMI < 25 kg/m2. WHAT IS KNOWN ALREADY: PCOS is associated
      with insulin resistance and increased prevalence of prediabetes and Type 2
      diabetes (T2D) which is closely linked to obesity and possibly age, ethnicity and
      PCOS phenotype. Several guidelines recommend OGTT upon diagnosis of PCOS and
      during follow-up. STUDY DESIGN, SIZE, DURATION: A Nordic cross-sectional study
      including 876 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 876 Nordic
      women with PCOS, aged 14-57 years, were examined for T2D and prediabetes
      (impaired glucose tolerance [IGT] or impaired fasting glucose (IFG) by OGTT. MAIN
      RESULT AND THE ROLE OF CHANCE: Of all study subjects 3% (23/876) had T2D, 23%
      (204/876) prediabetes and 74% (649/876) had normal glucose tolerance (NGT).
      Increased BMI and waist circumference were significantly (P < 0.001) associated
      with prevalence of prediabetes and T2D. No normal-weight woman (BMI < 25 kg/m2)
      was diagnosed with T2D. The prevalence of BMI >= 25 kg/m2 was 66% (578/ 876). 91%
      of women (21/23) with T2D had BMI >= 30 kg/m2. Testosterone levels and PCOS
      phenotype did not predict 2-h glucose levels during OGTT after adjustment for BMI
      and age. LIMITATIONS, REASONS FOR CAUTION: The present study included cross
      sectional data and prospective studies are needed to confirm our results. These
      results may not apply to populations of other ethnic origin. WIDER IMPLICATIONS
      OF THE FINDINGS: Routine OGTT may not be indicated in normal-weight women with
      PCOS. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

PMID- 29040531
TI  - Survival analysis of the association between antenatal care attendance and
      neonatal mortality in 57 low- and middle-income countries.
AB  - Background: Neonatal mortality is unacceptably high in most low- and middle
      income countries (LMICs). In these countries, where access to emergency obstetric
      services is limited, antenatal care (ANC) utilization offers improved maternal
      health and birth outcomes. However, evidence for this is scanty and mixed. We
      explored the association between attendance for ANC and survival of neonates in
      57 LMICs. Methods: Employing standardized protocols to ensure comparison across
      countries, we used nationally representative cross-sectional data from 57 LMICs
      (N = 464 728) to investigate the association between ANC visits and neonatal
      mortality. Cox proportional hazards multivariable regression models and meta
      regression analysis were used to analyse pooled data from the countries. Kaplan
      Meier survival curves were used to describe the patterns of neonatal survival in
      each region. Results: After adjusting for potential confounding factors, we found
      55% lower risk of neonatal mortality [hazard ratio (HR) 0.45, 95% confidence
      interval (CI) 0.42-0.48] among women who met both WHO recommendations for ANC
      (first visit within the first trimester and at least four visits during
      pregnancy) in pooled analysis. Furthermore, meta-analysis of country-level risk
      shows 32% lower risk of neonatal mortality (HR 0.68, 95% CI 0.61-0.75) among
      those who met at least one WHO recommendation. In addition, ANC attendance was
      associated with lower neonatal mortality in all the regions except in the Middle
      East and North Africa. Conclusions: ANC attendance is protective against neonatal
      mortality in the LMICs studied, although differences exist across countries and
      regions. Increasing ANC visits, along with other known effective interventions,
      can improve neonatal survival in these countries.

PMID- 29040532
TI  - Corrigendum: Cohort Profile: Pregnancy And Childhood Epigenetics (PACE)
      Consortium.

PMID- 29040533
TI  - Hippocampal phosphorylated tau induced cognitive decline, dendritic spine loss
      and mitochondrial abnormalities in a mouse model of Alzheimer's disease.
AB  - The purpose of our study was to understand the toxic effects of hippocampal
      phosphorylated tau in tau mice. Using rotarod and Morris water maze (MWM) tests,
      immunoblotting and immunofluorescence, Golgi-Cox staining and transmission
      electron microscopy, we assessed cognitive behavior, measured protein levels of
      mitochondrial dynamics, MAP2, total and phosphorylated tau, and quantified
      dendritic spines and mitochondrial number and length in 12-month-old tau mice
      with P301L mutation. Mitochondrial function was assessed by measuring the levels
      of H2O2, lipid peroxidation, cytochrome oxidase activity and mitochondrial ATP.
      MWM and rotarod tests revealed that hippocampal learning and memory and motor
      learning and coordination were impaired in tau mice relative to wild-type (WT)
      mice. Increased levels of mitochondrial fission proteins, Drp1 and Fis1 and
      decreased levels of mitochondrial fusion proteins, Mfn1, Mfn2 and Opa1 were found
      in 12-month-old tau mice relative to age-matched WT mice, indicating that the
      presence of abnormal mitochondrial dynamics in tau mice. Decreased levels of
      dendritic protein, MAP2 and increased levels of total and phosphorylated tau
      proteins were found in tau mice relative to WT mice. Mitochondrial function was
      defective. Golgi-Cox staining analysis revealed that dendritic spines are
      significantly reduced. Transmission electron microscopy revealed significantly
      increased mitochondrial numbers and reduced mitochondrial length in tau mice.
      These findings suggest that hippocampal accumulation of phosphorylated tau is
      responsible for abnormal mitochondrial dynamics and reducing dendritic protein
      MAP2 and dendritic spines and hippocampal based learning and memory impairments,
      and mitochondrial structural and functional changes in tau mice. Based on these
      observations, we propose that reduced hippocampal phosphorylated tau is an
      important therapeutic strategy for AD and other tauopathies.

PMID- 29040536
TI  - Due diligence in the open-access explosion era: choosing a reputable journal for
      publication.
AB  - Faculty are required to publish. Naive and "in-a-hurry-to-publish" authors seek
      to publish in journals where manuscripts are rapidly accepted. Others may
      innocently submit to one of an increasing number of questionable/predatory
      journals, where predatory is defined as practices of publishing journals for
      exploitation of author-pays, open-access publication model by charging authors
      publication fees for publisher profit without provision of expected services
      (expert peer review, editing, archiving, and indexing published manuscripts) and
      promising almost instant publication. Authors may intentionally submit
      manuscripts to predatory journals for rapid publication without concern for
      journal quality. A brief summary of the open access "movement," suggestions for
      selecting reputable open access journals, and suggestion for avoiding predatory
      publishers/journals are described. The purpose is to alert junior and seasoned
      faculty about predatory publishers included among available open access journal
      listings. Brief review of open access publication, predatory/questionable journal
      characteristics, suggestions for selecting reputable open access journals and
      avoiding predatory publishers/journals are described. Time is required for
      intentionally performing due diligence in open access journal selection, based on
      publisher/journal quality, prior to manuscript submission or authors must be able
      to successfully withdraw manuscripts when submission to a questionable or
      predatory journal is discovered.

PMID- 29040534
TI  - Macrophages escape Klotho gene silencing in the mdx mouse model of Duchenne
      muscular dystrophy and promote muscle growth and increase satellite cell numbers
      through a Klotho-mediated pathway.
AB  - Duchenne muscular dystrophy (DMD) is a muscle wasting disease in which
      inflammation influences the severity of pathology. We found that the onset of
      muscle inflammation in the mdx mouse model of DMD coincides with large increases
      in expression of pro-inflammatory cytokines [tumor necrosis factor-alpha
      (TNFalpha); interferon gamma (IFNgamma)] and dramatic reductions of the pro
      myogenic protein Klotho in muscle cells and large increases of Klotho in pro
      regenerative, CD206+ macrophages. Furthermore, TNFalpha and IFNgamma treatments
      reduced Klotho in muscle cells and increased Klotho in macrophages. Because
      CD206+/Klotho+ macrophages were concentrated at sites of muscle regeneration, we
      tested whether macrophage-derived Klotho promotes myogenesis. Klotho transgenic
      macrophages had a pro-proliferative influence on muscle cells that was ablated by
      neutralizing antibodies to Klotho and conditioned media from Klotho mutant
      macrophages did not increase muscle cell proliferation in vitro. In addition,
      transplantation of bone marrow cells from Klotho transgenic mice into mdx
      recipients increased numbers of myogenic cells and increased the size of muscle
      fibers. Klotho also acted directly on macrophages, stimulating their secretion of
      TNFalpha. Because TNFalpha is a muscle mitogen, we tested whether the pro
      proliferative effects of Klotho on muscle cells were mediated by TNFalpha and
      found that increased proliferation caused by Klotho was reduced by anti-TNFalpha.
      Collectively, these data show that pro-inflammatory cytokines contribute to
      silencing of Klotho in dystrophic muscle, but increase Klotho expression by
      macrophages. Our findings also show that macrophage-derived Klotho can promote
      muscle regeneration by expanding populations of muscle stem cells and increasing
      muscle fiber growth in dystrophic muscle.

PMID- 29040537
TI  - Chromosomal abnormalities in 1663 infertile men with azoospermia: the clinical
      consequences.
AB  - STUDY QUESTION: What is the prevalence of chromosomal abnormalities in
      azoospermic men and what are the clinical consequences in terms of increased risk
      for absent spermatogenesis, miscarriages and offspring with congenital
      malformations? SUMMARY ANSWER: The prevalence of chromosomal abnormalities in
      azoospermia was 14.4%, and the number of azoospermic men needed to be screened
      (NNS) to identify one man with a chromosomal abnormality with increased risk for
      absence of spermatogenesis was 72, to prevent one miscarriage 370-739 and to
      prevent one child with congenital malformations 4751-23 757. WHAT IS KNOWN
      ALREADY: Infertility guidelines worldwide advise screening of non-iatrogenic
      azoospermic men for chromosomal abnormalities, but only few data are available on
      the clinical consequences of this screening strategy. STUDY DESIGN, SIZE,
      DURATION: This retrospective multicentre cross-sectional study of non-iatrogenic
      azoospermic men was performed at the University Hospital Brussels, Belgium, and
      the University Medical Centre Groningen, The Netherlands, between January 2000
      and July 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Analysis of clinical
      registries retrospectively identified 1663 non-iatrogenic azoospermic men with
      available results of karyotyping and FSH serum levels. Iatrogenic azoospermia was
      an exclusion criterion, defined as azoospermia after spermatotoxic medical
      treatment, exogenous androgen suppletion or vasectomy and/or vasovasostomy. Also,
      men with a clinical diagnosis of anejaculation or hypogonadotropic hypo
      androgenism and/or FSH values <1.0 U/l were excluded. Chromosomal abnormalities
      were categorized according to their (theoretical) impact on clinical consequences
      for the patient (i.e. an increased risk for absence of spermatogenesis) and
      adverse pregnancy outcomes (i.e. miscarriage or offspring with congenital
      malformations), in both normogonadotropic (FSH < 10 U/l) and hypergonadotropic
      (FSH >= 10 U/l) azoospermia. We estimated the NNS for chromosomal abnormalities
      to identify one man with absence of spermatogenesis and to prevent one
      miscarriage or one child with congenital malformations, and calculated the
      surgical sperm retrieval rates per chromosomal abnormality. MAIN RESULTS AND THE
      ROLE OF CHANCE: The overall prevalence of chromosomal abnormalities in
      azoospermia was 14.4% (95% CI 12.7-16.1%), its prevalence being higher in
      hypergonadotropic azoospermia (20.2%, 95% CI 17.8-22.7%) compared to
      normogonadotropic azoospermia (4.9%, 95% CI 3.2-6.6%, P < 0.001). Klinefelter
      syndrome accounted for 83% (95% CI 77-87%) of abnormalities in hypergonadotropic
      azoospermia. The NNS to identify one man with increased risk for absence of
      spermatogenesis was 72, to prevent one miscarriage 370-739, and to prevent one
      child with congenital malformations 4751-23 757. There was no clinically
      significant difference in NNS between men with normogonadotropic and
      hypergonadotropic azoospermia. The surgical sperm retrieval rate was
      significantly higher in azoospermic men with a normal karyotype (60%, 95% CI 57.7
      63.1%) compared to men with a chromosomal abnormality (32%, 95% CI 25.9-39.0%, P
      < 0.001). The sperm retrieval rate in Klinefelter syndrome was 28% (95% CI 20.7
      35.0%). LIMITATIONS, REASONS FOR CAUTION: The absolute number of chromosomal
      abnormalities associated with clinical consequences and adverse pregnancy
      outcomes in our study was limited, thereby increasing the role of chance.
      Further, as there are currently no large series on outcomes of pregnancies in men
      with chromosomal abnormalities, our conclusions are partly based on assumptions
      derived from the literature. WIDER IMPLICATIONS OF THE FINDINGS: The NNS found
      can be used in future cost-effectiveness studies and the evaluation of current
      guidelines on karyotyping in non-iatrogenic azoospermia. STUDY FUNDING/COMPETING
      INTEREST(S): None to declare.

PMID- 29040538
TI  - Immobilization or mobilization after IUI: an RCT.
AB  - STUDY QUESTION: Does 15 min of immobilization after IUI improve pregnancy rates?
      SUMMARY ANSWER: Immobilization for 15 min after IUI does not improve pregnancy
      rates. WHAT IS KNOWN ALREADY: Prior RCTs report a beneficial effect of supine
      immobilization for 15 min following IUI compared to immediate mobilization,
      however, these studies can be criticized. Given the importance for the logistics
      in daily practice and the lack of biological plausibility we planned a
      replication study prior to potential implementation of this procedure. STUDY
      DESIGN, SIZE, DURATION: A single centre RCT, based in an academic setting in the
      Netherlands, was performed. Participants were randomly assigned for 15 min of
      supine immobilization following IUI for a maximum of six cycles compared to the
      standard procedure of immediate mobilization following IUI. Participants and
      caregivers were not blinded to group assignment. An independent researcher used
      computer-generated tables to allocate treatments. Stratification occurred to the
      indication of IUI (unexplained or mild male subfertility). Revelation of
      allocation took place just before the insemination by the caregiver. The primary
      outcome was ongoing pregnancy rate per couple. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: A total of 498 couples diagnosed with unexplained or mild male
      subfertility and an indication for treatment with IUI were approached and
      randomized in the study, of which 244 participants were assigned to 15 min of
      supine immobilization and 254 participants to immediate mobilization. MAIN
      RESULTS AND THE ROLE OF CHANCE: Participant characteristics were comparable
      between the groups, and 236 participants were analysed in the immobilization
      group, versus 245 in the mobilization group. The ongoing pregnancy rate per
      couple was not found to be superior in the immobilization group (one-sided P
      value = 0.97) with 76/236 ongoing pregnancies (32.2%) being accomplished in the
      immobilization and 98/245 ongoing pregnancies (40.0%) in the immediate
      mobilization group (relative risk 0.81; 95% CI [0.63, 1.02], risk difference: 
      7.8%, 95% CI [-16.4%, 0.8%]). No difference was found in miscarriage rate,
      multiple gestation rate, live birth rate and time to pregnancy between the
      groups. LIMITATIONS, REASONS FOR CAUTION: Owing to discontinuation of the planned
      treatment not all participants reached six IUI cycles or an ongoing pregnancy.
      However, this is as expected in IUI treatment and mirrors clinical practice.
      These participants were equally distributed across the two groups. Women with
      tubal pathology and endocrine disorders were excluded for this trial, and this
      might narrow generalizability. WIDER IMPLICATIONS OF THE FINDINGS: This study
      shows no positive effect of 15 min of immobilization following IUI on pregnancy
      rates. Based on available evidence today, including our study, a possible
      beneficial effect of supine immobilization after IUI is at least doubtful and
      straightforward implementation does not seem to be justified. STUDY
      FUNDING/COMPETING INTEREST(S): No funding was received. All authors have nothing
      to disclose. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR 2418. TRIAL
      REGISTRATION DATE: 20 July 2010. DATE OF FIRST PATIENT's ENROLMENT: 11 August
      2010.

PMID- 29040539
TI  - Explaining recent mortality trends among younger and middle-aged White Americans.
AB  - Background: Recent research has suggested that increases in mortality among
      middle-aged US Whites are being driven by suicides and poisonings from alcohol
      and drug use. Increases in these 'despair' deaths have been argued to reflect a
      cohort-based epidemic of pain and distress among middle-aged US Whites. Methods:
      We examine trends in all-cause and cause-specific mortality rates among younger
      and middle-aged US White men and women between 1980 and 2014, using official US
      mortality data. We estimate trends in cause-specific mortality from suicides,
      alcohol-related deaths, drug-related deaths, 'metabolic diseases' (i.e. deaths
      from heart diseases, diabetes, obesity and/or hypertension), and residual deaths
      from extrinsic causes (i.e. causes external to the body). We examine variation in
      mortality trends by gender, age and cause of death, and decompose trends into
      period- and cohort-based variation. Results: Trends in middle-aged US White
      mortality vary considerably by cause and gender. The relative contribution to
      overall mortality rates from drug-related deaths has increased dramatically since
      the early 1990s, but the contributions from suicide and alcohol-related deaths
      have remained stable. Rising mortality from drug-related deaths exhibit strong
      period-based patterns. Declines in deaths from metabolic diseases have slowed for
      middle-aged White men and have stalled for middle-aged White women, and exhibit
      strong cohort-based patterns. Conclusions: We find little empirical support for
      the pain- and distress-based explanations for rising mortality in the US White
      population. Instead, recent mortality increases among younger and middle-aged US
      White men and women have likely been shaped by the US opiate epidemic and an
      expanding obesogenic environment.

PMID- 29040540
TI  - New debate: is it time for infertility weight-loss programmes to be couple-based?
AB  - With obesity on the rise in the general population, it has also become more
      prevalent among people of reproductive age. Weight loss has shown benefits in
      overweight women and men experiencing fertility problems. However, the existing
      weight-loss interventions for individuals with infertility are associated with
      high drop-out rates and limited success. In this article, we argue for the
      development of weight-loss programmes targeting couples, as couples are routinely
      seen in fertility clinics, rather than individuals. Couples may have correlated
      weights, and similar eating and activity patterns. Involving both partners may
      facilitate mutual support, behaviour change, weight loss and programme
      continuation, at very little additional cost. A successful couple-based
      intervention could improve the chances of achieving pregnancy and delivering a
      healthy baby, with a reduction in pregnancy complications. In the longer run,
      both partners and their baby could benefit from maintained behaviour change with
      better health across the lifespan. We conclude that there is a need for research
      to systematically develop a couple-based weight-loss intervention with state-of
      the-art design that is tailored to both partners' needs.

PMID- 29040541
TI  - Placental Nano-vesicles Target to Specific Organs and Modulate Vascular Tone In
      Vivo.
AB  - STUDY QUESTION: How do nano-vesicles extruded from normal first trimester human
      placentae affect maternal vascular function? SUMMARY ANSWER: Placental nano
      vesicles affect the ability of systemic mesenteric arteries to undergo
      endothelium- and nitric oxide- (NO-) dependent vasodilation in vivo in pregnant
      mice. WHAT IS KNOWN ALREADY: Dramatic cardiovascular adaptations occur during
      human pregnancy, including a substantial decrease in total peripheral resistance
      in the first trimester. The human placenta constantly extrudes extracellular
      vesicles that can enter the maternal circulation and these vesicles may play an
      important role in feto-maternal communication. STUDY DESIGN, SIZE, DURATION:
      Human placental nano-vesicles were administered into CD1 mice via a tail vein and
      their localization and vascular effects at 30 min and 24 h post-injection were
      investigated. PARTICIPANTS/MATERIALS, SETTING, METHODS: Nano-vesicles from normal
      first trimester human placentae were collected and administered into pregnant
      (D12.5) or non-pregnant female mice. After either 30 min or 24 h of exposure, all
      major organs were dissected for imaging (n = 7 at each time point) while uterine
      and mesenteric arteries were dissected for wire myography (n = 6 at each time
      point). Additional in vitro studies using HMEC-1 endothelial cells were also
      conducted to investigate the kinetics of interaction between placental nano
      vesicles and endothelial cells. MAIN RESULTS AND THE ROLE OF CHANCE: Nano
      vesicles from first trimester human placentae localized to the lungs, liver and
      kidneys 24 h after injection into pregnant mice (n = 7). Exposure of pregnant
      mice to placental nano-vesicles for 30 min in vivo increased the vasodilatory
      response of mesenteric arteries to acetylcholine, while exposure for 24 h had the
      opposite effect (P < 0.05, n = 6). These responses were prevented by L-NAME, an
      NO synthase inhibitor. Placental nano-vesicles did not affect the function of
      uterine arteries or mesenteric arteries from non-pregnant mice. Placental nano
      vesicles rapidly interacted with endothelial cells via a combination of
      phagocytosis, endocytosis and cell surface binding in vitro. LARGE SCALE DATA:
      N/A. LIMITATIONS REASONS FOR CAUTION: As it is not ethical to administer labelled
      placental nano-vesicles to pregnant women, pregnant CD1 mice were used as a model
      of pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to
      report the localization of placental nano-vesicles and their vascular effects in
      vivo. This work provides new insight into how the dramatic maternal
      cardiovascular adaptations to pregnancy may occur and indicates that placental
      extracellular vesicles may be important mediators of feto-maternal communication
      in a healthy pregnancy. STUDY FUNDING/COMPETING INTEREST(S): This research was
      supported by the Faculty of Medical and Health Science (FMHS) School of Medicine
      PBRF research fund to L.W.C. M.T. is a recipient of a University of Auckland
      Health Research Doctoral Scholarship and the Freemasons Postgraduate Scholarship.
      No authors have any competing interests to disclose.

PMID- 29040542
TI  - High adherence to the Mediterranean diet is associated with cardiovascular
      protection in higher but not in lower socioeconomic groups: prospective findings
      from the Moli-sani study.
AB  - Background: It is uncertain whether the cardiovascular benefits associated with
      Mediterranean diet (MD) may differ across socioeconomic groups. Methods:
      Prospective analysis on 18991 men and women aged >=35 years from the general
      population of the Moli-sani cohort (Italy). Adherence to MD was appraised by the
      Mediterranean diet score (MDS). Household income (euros/year) and educational
      level were used as indicators of socioeconomic status. Hazard ratios (HR) were
      calculated by multivariable Cox proportional hazard models. Results: Over 4.3
      years of follow-up, 252 cardiovascular disease (CVD) events occurred. Overall, a
      two-point increase in MDS was associated with 15% reduced CVD risk (95%
      confidence interval: 1% to 27%). Such association was evident in highly (HR =
      0.43; 0.25-0.72) but not in less (HR = 0.94; 0.78-1.14) educated subjects (P for
      interaction = 0.042). Similarly, CVD advantages associated with the MD were
      confined to the high household income group (HR = 0.39; 0.23-0.66, and HR = 1.01;
      0.79-1.29 for high- and low-income groups, respectively; P for interaction =
      0.0098). In a subgroup of individuals of different socioeconomic status but
      sharing similar MDS, diet-related disparities were found as different intakes of
      antioxidants and polyphenols, fatty acids, micronutrients, dietary antioxidant
      capacity, dietary diversity, organic vegetables and whole grain bread
      consumption. Conclusions: MD is associated with lower CVD risk but this
      relationship is confined to higher socioeconomic groups. In groups sharing
      similar scores of adherence to MD, diet-related disparities across socioeconomic
      groups persisted. These nutritional gaps may reasonably explain at least in part
      the socioeconomic pattern of CVD protection from the MD.

PMID- 29040543
TI  - Cohort Profile: The Oxford Biobank.

PMID- 29040545
TI  - Ethnicity and place: the geography of diabetes inequalities under a strong
      welfare state.
AB  - Background: The Nordic 'health paradox' designates the seemingly puzzling
      empirical reality in which, despite the presence of strong welfare policies
      targeting structural inequalities, distinct health disparities persist in
      Scandinavian societies. In Norway, previous research has shown that inequalities
      in diabetes prevalence are particularly salient, notably between ethnic groups.
      These have often been attributed to lifestyle, socioeconomic factors, or
      genetics. No previous research has sought to investigate the sociospatial
      mediation of diabetes inequities. Methods: In this article, we examine the social
      geography of diabetes in Oslo to examine whether the link between ethnicity and
      diabetes is confounded by place. We use data from the 2002 Oslo Health Study (n =
      17 325) to fit logistic regression models, assessing whether contextual factors,
      such as the concentration of fast food outlets, predict self-reported diabetes
      outcomes after controlling for relevant individual level covariates. We also test
      for spatial autocorrelation in the geographical distribution of diabetes.
      Results: The findings suggest that the organisation of urban space and the
      spatial distribution of health-related resources exert an independent effect on
      diabetes prevalence, controlling for ethnicity and other covariates. Living on
      the east side of Oslo increases the odds of suffering from diabetes by almost
      60%, whilst living in a neighbourhood characterized by a relative concentration
      of fast food and relative absence of healthy food shops and physical exercise
      facilities increases the odds by 30%. Conclusion: Spatial context and toxic
      environments contribute to diabetes inequalities in Oslo, Norway. Future research
      and policy-making should take the geography of health disparities into account.

PMID- 29040544
TI  - Mutation-specific downregulation of CFTR2 variants by gating potentiators.
AB  - Approximately 50% of cystic fibrosis (CF) patients are heterozygous with a rare
      mutation on at least one allele. Several mutants exhibit functional defects,
      correctable by gating potentiators. Long-term exposure (>=24 h) to the only
      available potentiator drug, VX-770, leads to the biochemical and functional
      downregulation of F508del-CFTR both in immortalized and primary human airway
      cells, and possibly other CF mutants, attenuating its beneficial effect. Based on
      these considerations, we wanted to determine the effect of chronic VX-770
      exposure on the functional and biochemical expression of rare CF
      processing/gating mutants in human airway epithelia. Expression of CFTR2 mutants
      was monitored in the human bronchial epithelial cell line (CFBE41o-) and in
      patient-derived conditionally reprogrammed bronchial and nasal epithelia by short
      circuit current measurements, cell surface ELISA and immunoblotting in the
      absence or presence of CFTR modulators. The VX-770 half-maximal effective (EC50)
      concentration for G551D-CFTR activation was ~0.63 MUM in human nasal epithelia,
      implying that comparable concentration is required in the lung to attain clinical
      benefit. Five of the twelve rare CFTR2 mutants were susceptible to ~20-70%
      downregulation by chronic VX-770 exposure with an IC50 of ~1-20 nM and to
      destabilization by other investigational potentiators, thereby diminishing the
      primary functional gain of CFTR modulators. Thus, chronic exposure to VX-770 and
      preclinical potentiators can destabilize CFTR2 mutants in human airway epithelial
      models in a mutation and compound specific manner. This highlights the importance
      of selecting potentiator drugs with minimal destabilizing effects on CF mutants,
      advocating a precision medicine approach.

PMID- 29040547
TI  - Urea production by yeasts other than Saccharomyces in food fermentation.
AB  - Urea is an important intermediate in the synthesis of carcinogenic ethyl
      carbamate in various food fermentations. Identifying urea-producing
      microorganisms can help control or reduce ethyl carbamate production. Using
      Chinese liquor fermentation as a model system, we identified the yeasts
      responsible for urea production. Urea production was positively correlated to the
      yeast population (R = 0.523, P = 0.045), and using high-throughput sequencing, we
      identified 26 yeast species. Partial least squares regression and correlation
      analysis indicated that Wickerhamomyces anomalus was the most important yeast to
      produce urea (variable importance plot = 1.927; R = 0.719, P = 0.002). Besides,
      we found that in W. anomalus the CAR1 gene (responsible for urea production) was
      67% identical to that of Saccharomyces cerevisiae. Wickerhamomyces anomalus
      produced more urea (910.0 MUg L-1) than S. cerevisiae (300.1 MUg L-1). Moreover,
      urea production increased to 1261.2 MUg L-1 when the two yeasts were co-cultured
      in a simulated fermentation, where the transcription activity of the CAR1 gene
      increased by 140% in W. anomalus and decreased by 40% in S. cerevisiae. Our
      findings confirm that a yeast other than Saccharomyces, namely W. anomalus,
      contributes more to urea formation in a simulated sorghum fermentation. These
      findings provide the basis for strategies to control or reduce ethyl carbamate
      formation.

PMID- 29040546
TI  - Variation and Functional Impact of Neanderthal Ancestry in Western Asia.
AB  - Neanderthals contributed genetic material to modern humans via multiple admixture
      events. Initial admixture events presumably occurred in Western Asia shortly
      after humans migrated out of Africa. Despite being a focal point of admixture,
      earlier studies indicate lower Neanderthal introgression rates in some Western
      Asian populations as compared with other Eurasian populations. To better
      understand the genome-wide and phenotypic impact of Neanderthal introgression in
      the region, we sequenced whole genomes of nine present-day Europeans, Africans,
      and the Western Asian Druze at high depth, and analyzed available whole genome
      data from various other populations, including 16 genomes from present-day
      Turkey. Our results confirmed previous observations that contemporary Western
      Asian populations, on an average, have lower levels of Neanderthal-introgressed
      DNA relative to other Eurasian populations. Modern Western Asians also show
      comparatively high variability in Neanderthal ancestry, which may be attributed
      to the complex demographic history of the region. We further replicated the
      previously described depletion of putatively functional sequences among
      Neanderthal-introgressed haplotypes. Still, we find dozens of common Neanderthal
      introgressed haplotypes in the Turkish sample associated with human phenotypes,
      including anthropometric and metabolic traits, as well as the immune response.
      One of these haplotypes is unusually long and harbors variants that affect the
      expression of members of the CCR gene family and are associated with celiac
      disease. Overall, our results paint a complex first picture of the genomic impact
      of Neanderthal introgression in the Western Asian populations.

PMID- 29040549
TI  - Cohort Profile Update: The Doetinchem Cohort Study 1987-2017: lifestyle, health
      and chronic diseases in a life course and ageing perspective.

PMID- 29040548
TI  - European Society of Cardiology smartphone and tablet applications for patients
      with atrial fibrillation and their health care providers.
AB  - We are in the midst of a digital revolution in health care, although the
      application of new and useful technology in routine clinical practice is
      variable. The Characterizing Atrial fibrillation by Translating its Causes into
      Health Modifiers in the Elderly (CATCH ME) Consortium, in collaboration with the
      European Society of Cardiology (ESC), has funded the creation of two applications
      (apps) in atrial fibrillation (AF) for use in smartphones and tablets. The
      patient app aims to enhance patient education, improve communication between
      patients and health care professionals, and encourage active patient involvement
      in the management of their condition. The health care professional app is
      designed as an interactive management tool incorporating the new ESC Practice
      Guidelines on AF and supported by the European Heart Rhythm Association (EHRA),
      with the aim of improving best practice approaches for the care of patients with
      AF. Both stand-alone apps are now freely available for Android and iOS devices
      though the Google Play, Amazon, and Apple stores. In this article, we outline the
      rationale for the design and implementation of these apps. Our objective is to
      demonstrate the value of integrating novel digital technology into clinical
      practice, with the potential for patient engagement, optimization of
      pharmacological and interventional therapy in AF, and ultimately to improve
      patient outcomes.

PMID- 29040550
TI  - Rescue of cell death and inflammation of a mouse model of complex 1-mediated
      vision loss by repurposed drug molecules.
AB  - Inherited mitochondrial optic neuropathies, such as Leber's hereditary optic
      neuropathy (LHON) and Autosomal dominant optic atrophy (ADOA) are caused by
      mutant mitochondrial proteins that lead to defects in mitochondrial complex 1
      driven ATP synthesis, and cause specific retinal ganglion cell (RGC) loss.
      Complex 1 defects also occur in patients with primary open angle glaucoma (POAG),
      in which there is specific RGC loss. The treatment of mitochondrial optic
      neuropathy in the US is only supportive. The Ndufs4 knockout (Ndufs4 KO) mouse is
      a mitochondrial complex 1-deficient model that leads to RGC loss and rapid vision
      loss and allows for streamlined testing of potential therapeutics. Preceding RGC
      loss in the Ndufs4 KO is the loss of starburst amacrine cells, which may be an
      important target in the mechanism of complex 1-deficient vision loss. Papaverine
      and zolpidem were recently shown to be protective of bioenergetic loss in cell
      models of optic neuropathy. Treatment of Ndufs4 KO mice with papaverine,
      zolpidem, and rapamycin-suppressed inflammation, prevented cell death, and
      protected from vision loss. Thus, in the Ndufs4 KO mouse model of mitochondrial
      optic neuropathy, papaverine and zolpidem provided significant protection from
      multiple pathophysiological features, and as approved drugs in wide human use
      could be considered for the novel indication of human optic neuropathy.

PMID- 29040552
TI  - Commentary: Leonard Darwin: politician, eugenist and protector of Darwin
      heritage.

PMID- 29040551
TI  - Cohort Profile: Stratifying Resilience and Depression Longitudinally (STRADL): a
      questionnaire follow-up of Generation Scotland: Scottish Family Health Study
      (GS:SFHS).

PMID- 29040553
TI  - Longitudinal depression or anxiety in mothers and offspring asthma: a Swedish
      population-based study.
AB  - Background: Previous research has found that maternal stress during pregnancy
      increases the risk of offspring asthma. However, whether this association is
      consistent with a causal interpretation has never been tested. The objective is
      to determine whether there is a critical exposure period for maternal depression
      or anxiety on offspring asthma or whether cumulative exposure is most important,
      and to investigate evidence of confounding. Methods: The study population
      included all children born in Sweden from July 2006 to December 2009 (n = 360
      526). Information about childhood asthma, maternal depression or anxiety
      (diagnosis or medication) and covariates was obtained from the Swedish national
      health registers. The associations between exposure periods (pre-conception,
      pregnancy, postnatal or current) and childhood asthma were estimated using
      structured life course approach hypothesis testing. Paternal and cousin analyses
      were used to test for evidence of confounding from shared genes and environment.
      Results: For childhood asthma, cumulative exposure best described the effect of
      exposure to maternal depression or anxiety up to a maximum of any two exposure
      periods [adjusted odds ratio 1.44, 95% confidence interval (CI) 1.38, 1.52]. The
      hypotheses of a critical period were not supported. The paternal and cousin
      analyses indicated minimal influence from familial confounding. Conclusions:
      These findings support an association between cumulative exposure to maternal
      depression or anxiety and asthma development in offspring. This association is
      unique for maternal depression or anxiety and not due to familial confounding.
      The clinical implication is that effective psychological management of women with
      chronic distress may reduce offspring asthma risk.

PMID- 29040554
TI  - Frailty syndrome: an emerging clinical problem in the everyday management of
      clinical arrhythmias. The results of the European Heart Rhythm Association
      survey.
AB  - The age of patients presenting with complex arrhythmias is increasing. Frailty is
      a multifaceted syndrome characterized by an increased vulnerability to stressors
      and a decreased ability to maintain homeostasis. The prevalence of frailty is
      associated with age. The aims of this European Heart Rhythm Association (EHRA) EP
      Wire survey were to evaluate the proportion of patients with frailty and its
      influence on the clinical management of arrhythmias. A total of 41 centres
      members of the EHRA Electrophysiology Research Network-in 14 European countries
      completed the web-based questionnaire in June 2017. Patients over 70 years
      represented 53% of the total treated population, with the proportion of frail
      elderly individuals reaching approximately 10%; 91.7% of the responding centres
      reported treating frail subjects in the previous year. The respondents usually
      recognized frailty based on the presence of problems of mobility, nutrition, and
      cognition and inappropriate loss of body weight and muscle mass. Renal failure,
      dementia, disability, atrial fibrillation, heart failure, falls, and cancer were
      reported to characterize the elderly frail individuals. Atrial fibrillation was
      considered the prevalent arrhythmia associated with frailty by 72% of the
      responding centres, and for stroke prevention, non-vitamin K antagonist oral
      anticoagulants were preferred. None of the respondents considered withholding the
      prevention of thrombo-embolic events in subjects with a history of falls. All
      participants have agreed that cardiac resynchronization therapy exerts positive
      effects including improvement in cardiac, physical, and cognitive performance and
      quality of life. The majority of respondents preferred an Arrhythmia Team to
      manage this special population of elderly patients, and many would like having a
      simple tool to quickly assess the presence of frailty to guide their decisions,
      particularly on the use of complex cardiac implantable electrical devices
      (CIEDs). In conclusion, the complex clinical condition in frail patients
      presenting with arrhythmias warrants an integrated multidisciplinary approach
      both for the management of rhythm disturbances and for the decision on using
      CIEDs.

PMID- 29040555
TI  - The effectiveness of varenicline versus nicotine replacement therapy on long-term
      smoking cessation in primary care: a prospective cohort study of electronic
      medical records.
AB  - Background: There is limited evidence about the effectiveness of varenicline and
      nicotine replacement therapy (NRT) for long-term smoking cessation in primary
      care, or whether the treatment effectiveness differs by socioeconomic position
      (SEP). Therefore, we estimated the long-term effectiveness of varenicline versus
      NRT (> 2 years) on smoking cessation, and investigated whether effectiveness
      differs by SEP. Methods: This is a prospective cohort study of electronic medical
      records from 654 general practices in England, within the Clinical Practice
      Research Datalink, using three different analytical methods: multivariable
      logistic regression, propensity score matching and instrumental variable
      analyses. Exposure was prescription of varenicline versus NRT, and the primary
      outcome was smoking cessation at 2 years' follow-up; outcome was also assessed at
      3, 6, and 9 months, and at 1 and 4 years after exposure. SEP was defined using
      the Index of Multiple Deprivation. Results: At 2 years, 28.8% (N = 20 362/70 610)
      of participants prescribed varenicline and 24.3% (N = 36 268/149 526) of those
      prescribed NRT quit; adjusted odds ratio was 1.26 [95% confidence interval (CI):
      1.23 to 1.29], P < 0.0001. The association persisted for up to 4 years and was
      consistent across all analyses. We found little evidence that the effectiveness
      of varenicline differed greatly by SEP. However, patients from areas of higher
      deprivation were less likely to be prescribed varenicline; adjusted odds ratio
      was 0.91 (95% CI: 0.90 to 0.92), P < 0.0001. Conclusions: Patients prescribed
      varenicline were more likely to be abstinent up to 4 years after first
      prescription than those prescribed NRT. In combination with other evidence, the
      results from this study may be used to update clinical guidelines on the use of
      varenicline for smoking cessation.

PMID- 29040556
TI  - Cohort Profile: The PERU MIGRANT Study-A prospective cohort study of rural
      dwellers, urban dwellers and rural-to-urban migrants in Peru.

PMID- 29040557
TI  - Divergence and convergence in cause-specific premature adult mortality in Mexico
      and US Mexican Hispanics from 1995 to 2015: analyses of 4.9 million individual
      deaths.
AB  - Background: Mexicans and US Mexican Hispanics share modifiable determinants of
      premature mortality. We compared trends in mortality at ages 30-69 in Mexico and
      among US Mexican Hispanics from 1995 to 2015. Methods: We examined nationally
      representative statistics on 4.2 million Mexican and 0.7 million US deaths to
      examine cause-specific mortality. We used lung cancer indexed methods to estimate
      smoking-attributable deaths stratified by high and lower burden Mexican states.
      Results: In 1995-99, Mexican men had about 30% higher relative risk of death from
      all causes than US Mexican Hispanic men, and this difference nearly doubled to
      58% by 2010-15. The divergence between Mexican and US Mexican Hispanic women over
      this time period was less marked. Among US Mexican Hispanics, declines in the
      risk of smoking-attributable death constituted about 25-30% of the declines in
      the overall risk of death. However, among Mexican men the declines in the risk of
      smoking-attributable deaths were offset by increases in causes of death not due
      to smoking. Homicide rates (mostly from guns) rose among men in Mexico from 2005
      to 2010, but not among Mexican women or US Mexican Hispanic men or women. The
      probability at 30-69 years of death from cardiac disease diverged significantly
      between Mexicans and US Mexican Hispanics, reaching 10% and 5% for men, and 7%
      and 2% for women, respectively. Conclusions: Large differences in premature
      mortality between otherwise genetically and culturally similar groups arise from
      a few modifiable factors, most notably smoking, untreated diabetes and homicide.

PMID- 29040559
TI  - Cohort Profile: The Early Language in Victoria Study (ELVS).

PMID- 29040558
TI  - Constitutively-active FGFR3 disrupts primary cilium length and IFT20 trafficking
      in various chondrocyte models of achondroplasia.
AB  - Fibroblast growth factor receptor 3 (FGFR3) gain-of-function mutations cause
      dwarfisms, including achondroplasia (ACH) and thanatophoric dysplasia (TD). The
      constitutive activation of FGFR3 disrupts the normal process of skeletal growth.
      Bone-growth anomalies have been identified in skeletal ciliopathies, in which
      primary cilia (PC) function is disrupted. In human ACH and TD, the impact of
      FGFR3 mutations on PC in growth plate cartilage remains unknown. Here we showed
      that in chondrocytes from human (ACH, TD) and mouse Fgfr3Y367C/+ cartilage, the
      constitutively active FGFR3 perturbed PC length and the sorting and trafficking
      of intraflagellar transport (IFT) 20 to the PC. We demonstrated that inhibiting
      FGFR3 with FGFR inhibitor, PD173074, rescued both PC length and IFT20
      trafficking. We also studied the impact of rapamycin, an inhibitor of mammalian
      target of rapamycin (mTOR) pathway. Interestingly, mTOR inhibition also rescued
      PC length and IFT20 trafficking. Together, we provide evidence that the growth
      plate defects ascribed to FGFR3-related dwarfisms are potentially due to loss of
      PC function, and these dwarfisms may represent a novel type of skeletal disorders
      with defective ciliogenesis.

PMID- 29040560
TI  - Cohort Profile: The Finnish Mobile Clinic Health Surveys FMC, FMCF and MFS.

PMID- 29040561
TI  - Prospective evaluation of a continuous infusion vancomycin dosing nomogram in
      critically ill patients undergoing continuous venovenous haemofiltration.
AB  - Objectives: The most optimal method of attaining therapeutic vancomycin
      concentrations during continuous venovenous haemofiltration (CVVH) remains
      unclear. Studies have shown continuous infusion vancomycin (CIV) achieves target
      concentrations more rapidly and consistently when compared with intermittent
      infusion. Positive correlations between CVVH intensity and vancomycin clearance
      (CLvanc) have been noted. This study is the first to evaluate a CIV regimen in
      patients undergoing CVVH that incorporates weight-based CVVH intensity (mL/kg/h)
      into the dosing nomogram. Methods: This was a prospective, observational study of
      patients undergoing CVVH and receiving CIV based on the nomogram. The primary
      outcome was achievement of a therapeutic vancomycin concentration (15-25 mg/L) at
      24 h. Secondary outcomes included the achievement of therapeutic concentrations
      at 48 and 72 h. Results: The nomogram was analysed in 52 critically ill adults.
      Vancomycin concentrations were therapeutic in 43/52 patients (82.7%) at 24 h. Of
      the nine patients who were not therapeutic at 24 h, seven were supratherapeutic
      and two were subtherapeutic. The mean (SD) concentration was 20.1 (4.2)  mg/L at
      24 h, 20.7 (3.7) mg/L at 48 h and 21.9 (3.5)  mg/L at 72 h. Patients with CVVH
      intensity >20 mL/kg/h experienced higher CLvanc at 24 h compared with patients
      with CVVH intensity <20 mL/kg/h (3.1 versus 2.6 L/h; P = 0.013). Conclusions: By
      incorporating CVVH intensity into the CIV dosing nomogram, the majority of
      patients achieved therapeutic concentrations at 24 h and maintained them within
      range at 48 and 72 h. Additional studies are required to validate this nomogram
      before widespread implementation may be considered.

PMID- 29040562
TI  - Collider scope: when selection bias can substantially influence observed
      associations.
AB  - Large-scale cross-sectional and cohort studies have transformed our understanding
      of the genetic and environmental determinants of health outcomes. However, the
      representativeness of these samples may be limited-either through selection into
      studies, or by attrition from studies over time. Here we explore the potential
      impact of this selection bias on results obtained from these studies, from the
      perspective that this amounts to conditioning on a collider (i.e. a form of
      collider bias). Whereas it is acknowledged that selection bias will have a strong
      effect on representativeness and prevalence estimates, it is often assumed that
      it should not have a strong impact on estimates of associations. We argue that
      because selection can induce collider bias (which occurs when two variables
      independently influence a third variable, and that third variable is conditioned
      upon), selection can lead to substantially biased estimates of associations. In
      particular, selection related to phenotypes can bias associations with genetic
      variants associated with those phenotypes. In simulations, we show that even
      modest influences on selection into, or attrition from, a study can generate
      biased and potentially misleading estimates of both phenotypic and genotypic
      associations. Our results highlight the value of knowing which population your
      study sample is representative of. If the factors influencing selection and
      attrition are known, they can be adjusted for. For example, having DNA available
      on most participants in a birth cohort study offers the possibility of
      investigating the extent to which polygenic scores predict subsequent
      participation, which in turn would enable sensitivity analyses of the extent to
      which bias might distort estimates.

PMID- 29040563
TI  - Ten years of CAZypedia: a living encyclopedia of carbohydrate-active enzymes.
AB  - CAZypedia was initiated in 2007 to create a comprehensive, living encyclopedia of
      the carbohydrate-active enzymes (CAZymes) and associated carbohydrate-binding
      modules involved in the synthesis, modification and degradation of complex
      carbohydrates. CAZypedia is closely connected with the actively curated CAZy
      database, which provides a sequence-based foundation for the biochemical,
      mechanistic and structural characterization of these diverse proteins. Now
      celebrating its 10th anniversary online, CAZypedia is a successful example of
      dynamic, community-driven and expert-based biocuration. CAZypedia is an open
      access resource available at URL http://www.cazypedia.org.

PMID- 29040564
TI  - N-cadherin identifies human endometrial epithelial progenitor cells by in vitro
      stem cell assays.
AB  - STUDY QUESTION: Is there a specific surface marker that identifies human
      endometrial epithelial progenitor cells with adult stem cell activity using in
      vitro assays? SUMMARY ANSWER: N-cadherin isolates clonogenic, self-renewing human
      endometrial epithelial progenitor cells with high proliferative potential that
      differentiate into cytokeratin+ gland-like structures in vitro and identifies
      their location in some cells of gland profiles predominantly in basalis
      endometrium adjacent to the myometrium. WHAT IS KNOWN ALREADY: Human endometrium
      contains a small population of clonogenic, self-renewing epithelial cells with
      high proliferative potential that differentiate into large gland-like structures,
      but their identity and location is unknown. Stage-specific embryonic antigen-1
      (SSEA-1) distinguishes the epithelium of basalis from functionalis and is a
      marker of human post-menopausal (Post-M) endometrial epithelium. STUDY DESIGN,
      SIZE, DURATION: Prospective observational study of endometrial epithelial cells
      obtained from hysterectomy samples taken from 50 pre-menopausal (Pre-M) and 24
      Post-M women, of which 4 were from women who had taken daily estradiol valerate 2
      mg/day for 8 weeks prior. PARTICIPANTS/MATERIALS, SETTING, METHODS: Gene
      profiling was used to identify differentially expressed surface markers between
      fresh EpCAM (Epithelial Cell Adhesion Molecule)-magnetic bead-selected basalis
      like epithelial cells from Post-M endometrium compared with predominantly
      functionalis epithelial cells from Pre-M endometrium and validated by qRT-PCR. In
      vitro clonogenicity and self-renewal assays were used to assess the
      stem/progenitor cell properties of magnetic bead-sorted N-cadherin+ and N
      cadherin- epithelial cells. The cellular identity, location and phenotype of N
      cadherin+ cells was assessed by dual colour immunofluorescence and confocal
      microscopy for cytokeratin, proliferative status (Ki-67), ERalpha, SSEA-1, SOX9
      and epithelial mesenchymal transition (EMT) markers on full thickness human
      endometrium. MAIN RESULTS AND THE ROLE OF CHANCE: CDH2 (N-cadherin gene) was one
      of 11 surface molecules highly expressed in Post-M compared to Pre-M endometrial
      epithelial cells. N-cadherin+ cells comprise a median 16.7% (n = 8) and 20.2% (n
      = 5) of Pre-M endometrial epithelial cells by flow cytometry and magnetic bead
      sorting, respectively. N-cadherin+ epithelial cells from Pre-M endometrium were
      more clonogenic than N-cadherin- cells (n = 12, P = 0.003), underwent more
      population doublings (n = 7), showed greater capacity for serial cloning (n = 7)
      and differentiated into cytokeratin+ gland-like organoids. N-cadherin
      immunolocalised to the lateral and apical membrane of epithelial cells in the
      bases of glands in the basalis of Pre-M endometrium and Post-M gland profiles, co
      expressing cytokeratin, ERalpha but not SSEA-1 or SOX9, which localized on gland
      profiles proximal to N-cadherin+ cells. N-cadherin+ cells were quiescent (Ki-67-)
      in the basalis and in Post-M endometrial glands and co-localized with EMT markers
      vimentin and E-cadherin. LARGE SCALE DATA: The raw and processed data files from
      the gene microarray have been deposited in the National Center for Biotechnology
      Information Gene Expression Omnibus data set with accession number GSE35221.
      LIMITATIONS, REASONS FOR CAUTION: This is a descriptive study in human
      endometrium only using in vitro stem cell assays. The differential ability of N
      cadherin+ and N-cadherin-cells to generate endometrial glands in vivo was not
      determined. A small number of uterine tissues analysed contained adenomyosis for
      which N-cadherin has been implicated in epithelial-EMT. WIDER IMPLICATIONS OF THE
      FINDINGS: A new marker enriching for human endometrial epithelial progenitor
      cells identifies a different and potentially more primitive cell population than
      SSEA-1, suggesting a potential hierarchy of epithelial differentiation in the
      basalis. Using N-cadherin as a marker, the molecular and cellular characteristics
      of epithelial progenitor cells and their role in endometrial proliferative
      disorders including endometriosis, adenomyosis and thin dysfunctional endometrium
      can be investigated. STUDY FUNDING/COMPETING INTEREST(S): This research was
      supported by Cancer Council Victoria grant 491079 (C.E.G.) and Australian
      National Health and Medical Research Council grants 1021127 (C.E.G.), 1085435
      (C.E.G., J.A.D.), 145780 and 288713 (C.N.S.), RD Wright Career Development Award
      465121 (C.E.G.), Senior Research Fellowship 1042298 (C.E.G.), the Victorian
      Government's Operational Infrastructure Support and an Australian Postgraduate
      Award (HPTN), and China Council Scholarship (L.X.). The authors have nothing to
      declare.

PMID- 29040565
TI  - Refugees, migrants, and displaced populations: the United Nations New York
      Declaration and the WHO International Health Regulations.
AB  - The World Health Assembly approved the International Health Regulations (IHR)
      committing countries to strengthen their capacity to address public health
      emergencies of international concern. A mechanism to assess a country's capacity,
      the Joint External Evaluation (JEE), is a means to assist countries to assess
      their health system preparedness. The assessment teams include public health and
      veterinary experts, but include those with specialized knowledge about refugee,
      immigrant, and internally displaced persons situations. Such experts have not
      been regularly included in the JEE assessment teams previously. Particularly
      where there are significant existing or prospective populations of this cohort,
      the author asserts they need to be.

PMID- 29040566
TI  - Overlapping network meta-analyses on the same topic: survey of published studies.
AB  - Background: To assess how common it is for a published network meta-analysis
      (NMA) to have other published overlapping NMAs, and to evaluate these overlaps.
      Methods: A total of 88 NMAs of randomized controlled trials evaluating the
      comparative effectiveness of health interventions were randomly selected. For
      each of these, we searched for NMAs on the same topic. A random sample of 40
      pairs (an index NMA and one of its overlapping NMAs) was selected to assess the
      overlap in terms of nodes, treatments and references. The topic with the largest
      number of overlapping NMAs was described in depth. Results: In all, 68 of the 88
      index NMAs had at least one overlapping NMA: 77% [95% confidence interval (CI),
      69-86%]. We identified 515 pairs of overlapping NMAs. Among the 40 randomly
      selected pairs, 73% (95% CI, 58-88%) of nodes, 79% (95% CI, 72-86%) of treatments
      and 48% (95% CI, 37-59%) of references included in the index NMAs were also found
      in the respective overlapping NMAs. Efficacy of biologics in rheumatoid arthritis
      had the largest number of overlapping NMAs, with 28 NMAs published between 2003
      and 2014. Differences in selection and definition of nodes of treatments resulted
      in different network geometries. There were also differences in both the
      direction and the statistical significance of effects. Conclusions: Published
      NMAs exhibit extensive overlap and potential redundancy. Erratic retrieval of
      eligible trials, and lack of consensus on the range of interventions to be
      considered and how they might be merged or split in different nodes, may cause
      confusion.

PMID- 29040567
TI  - Effects of Insect Growth Regulators on Bagrada hilaris (Hemiptera: Pentatomidae).
AB  - Bagrada hilaris (Burmeister) (Hemiptera: Pentatomidae) is a serious pest of
      cruciferous crops in the central coast of California. Management of B. hilaris
      primarily involves the use of broad spectrum insecticides, such as pyrethroids
      and neonicotinoids, when the pest invades a crop field. Insect growth regulators
      (IGRs) are known for their efficacy on nymphal stages of B. hilaris, but little
      is known about their transovarial effects. Thus, the major objective of this
      study was to determine the transovarial effects of IGRs such as novaluron,
      diflubenzuron, and azadirachtin, when adults are exposed to direct topical
      spraying and dried residues. In addition, a direct topical spray of IGRs on older
      instars (fourth and fifth instars) was examined at 1-, 3-, and 7-d post
      treatment. The number of young instars (first and second instars) and adults was
      recorded up to ~31 d after exposure. In the topical spray assays, the number of
      young instars was significantly lower for novaluron, diflubenzuron, and
      azadirachtin than for the nontreated control. The number of young instars that
      emerged after novaluron treatment was low (0-11%). In the assays with dried
      residues, the number of young instars that developed was significantly lower for
      novaluron treatment than for the other IGRs and the nontreated control. There was
      no significant difference among diflubenzuron, azadirachtin, and nontreated
      control treatments in the development of young instars. In the assays with a
      topical spray of IGRs on older instars, significantly more nymphs died at 3 and 7
      d after exposure. The IGRs had no clear impact on adults.

PMID- 29040568
TI  - U-47700: A Not So New Opioid.
AB  - U-47700 was developed by the Upjohn Co. in the 1970s as part of their search for
      a selective MU-opioid agonist with similar potency as morphine. U-47700 has re
      emerged recently in the illicit drug market and is easily and cheaply obtained
      via the internet as well as on the street, many times falsely sold as another
      drug. Several fatalities from U-47700 have been reported in scientific
      literature, often in combination with other intoxicants. This case report
      describes the first death in south-central Kansas resulting solely from U-47700
      intoxication: a 26-year-old white male found dead in his bedroom with apparent
      drug paraphernalia. Autopsy findings were consistent with opioid overdose, but
      toxicological examination, utilizing immunoassay and instrumental techniques, was
      negative for opioids. U-47700 was detected in a comprehensive alkaloid screen by
      GC/MS and GC-NPD, and quantitation was performed using GC-NPD on a variety of
      specimens to provide a full tissue distribution. Quantitation of U-47700 in this
      individual revealed the following: heart blood 0.26 mg/L, femoral blood 0.40
      mg/L, vitreous fluid 0.09 mg/L, brain 0.38 mg/kg, liver 0.28 mg/kg and urine 4.6
      mg/L.

PMID- 29040569
TI  - Antiretroviral therapy use during pregnancy and adverse birth outcomes in South
      African women.
AB  - Background: Studies of antiretroviral therapy (ART) use during pregnancy in HIV
      infected women have suggested that ART exposure may be associated with adverse
      birth outcomes. However, there are few data from sub-Saharan Africa where HIV is
      most common, and few studies involving the World Health Organization's (WHO's)
      recommended first-line regimens. Methods: We enrolled consecutive HIV-infected
      pregnant women and a comparator cohort of uninfected women at a primary-level
      antenatal care facility in Cape Town, South Africa. Gestational assessment
      combined clinical history, examination and ultrasonography; outcomes included
      preterm (PTD), low birthweight (LBW) and small for gestational age (SGA)
      deliveries. In analysis we compared birth outcomes between HIV-infected and 
      uninfected women, and HIV-infected women who initiated ART before vs during
      pregnancy. Results: In 1554 women (mean age 29 years) with live singleton births
      at time of analysis, 82% were HIV-infected, 92% of whom received a first-line
      regimen of tenofovir, emtricitabine and efavirenz. Overall, higher levels of PTD
      [22% vs 13%; odds ratio (OR) 1.94, 95% confidence interval (CI): 1.34, 2.82] and
      LBW (14% vs 9%; OR 1.62, 95% CI: 1.05, 2.29) were observed in HIV-infected vs
      uninfected women, although SGA deliveries were similar (9% vs 11%; OR 1.06, 95%
      CI: 0.71, 1.61). Adjusting for demographic characteristics and HIV disease
      measures, HIV-infected (vs HIV-uninfected) women had persistently increased odds
      of PTD [adjusted odds ratio (AOR) 2.03; CI 1.33, 3.10]; associations with LBW
      were attenuated (AOR 1.47; CI 0.90, 2.40). Among all HIV-infected women, there
      appeared to be no association between the timing of ART initiation (before or
      during pregnancy) and adverse birth outcomes. Conclusions: These findings suggest
      that current WHO-recommended ART regimens appear relatively safe in pregnancy,
      although more data are required to understand the aetiology of preterm delivery
      in HIV-infected women using ART.

PMID- 29040570
TI  - Cumulative live birth rates following miscarriage in an initial complete cycle of
      IVF: a retrospective cohort study of 112 549 women.
AB  - STUDY QUESTION: In women undergoing IVF/ICSI who miscarry in their first complete
      cycle, what is the chance of a live birth in subsequent complete cycles, and how
      does this compare with those whose first complete cycle ends with live birth or
      without a pregnancy? SUMMARY ANSWER: After two further complete cycles of
      IVF/ICSI, women who had miscarried or had a live birth in their first complete
      cycle had a higher chance of live birth (40.9 and 49.0%, respectively) than those
      who had no pregnancies (30.1%). WHAT IS KNOWN ALREADY: Cumulative live birth
      rates (CLBRs) after one or more complete cycles of IVF have been reported
      previously, as have some of the risk factors associated with miscarriage, both in
      general populations and in those undergoing IVF. Chances of cumulative live birth
      after a number of complete IVF cycles involving replacement of fresh followed by
      frozen embryos after an initial miscarriage in a population undergoing IVF
      treatment have not been reported previously. STUDY DESIGN, SIZE, DURATION:
      National population-based cohort study of 112 549 women who started their first
      IVF treatment between 1999 and 2008. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Data from the UK Human Fertilisation and Embryology Authority (HFEA) register on
      IVF/ICSI treatments, using autologous gametes were analysed. CLBRs were estimated
      in women who (i) had miscarriage (and no live birth), (ii) at least one live
      birth or (iii) no pregnancy in their first complete cycle of IVF/ICSI (including
      fresh and frozen embryo transfers following a single oocyte retrieval episode). A
      multivariable analysis was performed to assess the effect of first complete cycle
      outcome on subsequent CLBRs after adjusting for confounding factors such as
      female age, duration of infertility and cause of infertility. MAIN RESULTS AND
      THE ROLE OF CHANCE: In their first complete cycle, 9321 (8.3%) women had at least
      one miscarriage (and no live birth); 33 152 (29.5%) had at least one live birth
      and 70 076 (62.3%) had no pregnancies. After two further complete cycles,
      conservative CLBRs (which assume that women who discontinued treatment
      subsequently never had a live birth) were 40.9, 49.0 and 30.1%, while optimal
      CLBRs (which assume that women who discontinue have the same chance of live birth
      as those treated) were 49.5, 57.9 and 38.4% in the miscarriage, live birth and no
      pregnancy groups respectively. Odds of cumulative live birth for women who
      miscarried in their first complete cycle were 42% higher than those who had no
      pregnancy [odds ratio (95% CI) = 1.42 (1.34, 1.50)], and twice as high for live
      birth versus no pregnancy [2.04 (1.89, 2.20)]. Negative predictors for live birth
      in all women included tubal infertility [0.88 (0.82, 0.94)] and increasing age
      [18-40 years = 0.94 (0.94, 0.95); >40 years = 0.63 (0.59, 0.66) per year].
      LIMITATIONS AND REASON FOR CAUTION: CLBRs could not be estimated for treatments
      occurring after September 2008 due to potentially incomplete data following
      regulatory changes regarding consent for data use in research. Additionally,
      covariates not included in the HFEA database (including BMI, smoking, previous
      history of miscarriage and gestational age at miscarriage) could not be adjusted
      for in our analysis. WIDER IMPLICATIONS OF THE FINDINGS: Miscarriage following
      IVF can be devastating for couples who are uncertain about their ultimate
      prognosis. Our findings will provide reassurance to these couples as they
      consider their options for continuing treatment. STUDY FUNDING/COMPETING
      INTEREST(S): N.J.C. received an Aberdeen Summer Research Scholarship funded by
      the Institute of Applied Health Sciences (University of Aberdeen), through the
      Aberdeen Clinical Academic Training Scheme. This work was supported by a Chief
      Scientist Office Postdoctoral Training Fellowship in Health Services Research and
      Health of the Public Research (Ref PDF/12/06). The views expressed here are those
      of the authors and not necessarily those of the Chief Scientist Office or the
      University of Aberdeen. The funders did not have any role in the study design; in
      the collection, analysis and interpretation of data; in the writing of the
      report; nor in the decision to submit the paper for publication. None of the
      authors has any conflicts of interest to declare.

PMID- 29040571
TI  - Patient-centered early pregnancy care: a systematic review of quantitative and
      qualitative studies on the perspectives of women and their partners.
AB  - BACKGROUND: Early pregnancy complications, defined as miscarriage, recurrent
      miscarriage or ectopic pregnancy, affect the physical and psychological well
      being of intended parents. Research in this field so far has focused mainly on
      improving accuracy of diagnostic tests and safety and effectiveness of
      therapeutic management. An overview of aspects of care valued by women and/or
      their partners is missing. OBJECTIVE AND RATIONALE: This systematic review aims
      to provide an overview of aspects of care valued by women and/or their partners
      faced with early pregnancy complications and to identify potential targets for
      improvement in early pregnancy healthcare. SEARCH METHODS: We searched five
      electronic databases for empirical quantitative or qualitative studies on
      patients' perspectives of early pregnancy care in July 2017. We first identified
      aspects of early pregnancy care valued by women and/or their partners based on
      qualitative and quantitative data and organized these aspects of care according
      to the eight dimensions of patient-centered care. Second, we extracted the
      assessment of service quality from women and/or their partners on each of these
      aspects of care based on quantitative data. Third, we combined the findings on
      patients' values with the findings of service quality assessment to identify
      potential targets for improvement in five groups according to how likely these
      targets are to require improvement. OUTCOMES: The search yielded 6240
      publications, of which 27 studies were eligible for inclusion in this review. All
      included studies focused on miscarriage or recurrent miscarriage care. We
      identified 24 valued aspects of care, which all covered the eight dimensions of
      patient-centered care. The most frequently reported valued aspect was 'being
      treated as an individual person experiencing a significant life event rather than
      a common condition'. Assessment of service quality from women and/or their
      partners was available for 13 of the 24 identified aspects of care. Quantitative
      studies all documented service quality as problematic for these 13 aspects of
      care. We thus identified 13 potential targets for improvement in the patient
      centeredness of miscarriage and recurrent miscarriage care of which none were
      very likely, four were likely, six were unlikely and three were very unlikely, to
      require improvement. The four likely potential targets for improvement were
      'Understandable information provision about the etiology of pregnancy', 'Staff
      discussing patients' distress', 'Informing patients on pregnancy loss in the
      presence of a friend or partner' and 'Staff performing follow-up phone calls to
      support their patients after a miscarriage'. WIDER IMPLICATIONS: It is important
      for clinicians to realize that women and their partners undergoing a miscarriage
      experience a significant live event and appreciate an individual approach. Future
      qualitative studies are needed to explore the identified potential targets for
      improvement of (recurrent) miscarriage care and to explore patients' perspectives
      in women suspected and treated for ectopic pregnancy.

PMID- 29040573
TI  - How much atopy is attributable to common childhood environmental exposures? A
      population-based birth cohort study followed to adulthood.
AB  - Background: The rising prevalence of atopic diseases implies a strong influence
      of environmental determinants. Epidemiological studies have identified several
      early life exposures that appear to influence the risk of developing atopic
      sensitization, but the combined influence of these exposures is unknown. We
      sought to estimate the proportion of atopy that could be attributed to common
      childhood exposures associated with atopic sensitization in adolescence and young
      adulthood. Methods: Atopic sensitization was measured by skin-prick tests for
      common aeroallergens in a population-based New Zealand birth cohort at ages 13
      and 32 years. The independent effects of previously identified risk and
      protective factors for atopic sensitization were assessed using multiple logistic
      regression. Population attributable fractions were calculated for atopic
      sensitization in childhood and adulthood. Results: Tobacco smoke exposure, dog
      and cat ownership, nail-biting and thumb-sucking, attending pre-school day care,
      and household crowding were associated with a lower risk of atopic sensitization
      whereas breastfeeding was associated with a higher risk. Population attributable
      fractions for combined effects of these environmental factors suggest that they
      may account for 58% of atopic sensitization at age 13 and 49% at age 32 years.
      Conclusions: A substantial proportion of atopic sensitization appears to be
      attributable to common childhood environmental and lifestyle factors, and the
      influence of these exposures persists into adulthood. The absolute risks
      attributable to these exposures will be different in other cohorts and we cannot
      assume that these associations are necessarily causal. Nevertheless, the findings
      suggest that identifiable childhood environmental factors contribute
      substantially to atopic sensitization.

PMID- 29040574
TI  - Integrating children's physical activity enjoyment into public health dialogue
      (United States).
AB  - Keywords: children, physical activity, public health.

PMID- 29040575
TI  - Role of tenofovir alafenamide in the jungle of antiretroviral prescription.

PMID- 29040572
TI  - Biallelic mutations in the ferredoxin reductase gene cause novel
      mitochondriopathy with optic atrophy.
AB  - Iron-sulfur (Fe-S) clusters are ubiquitous cofactors essential to various
      cellular processes, including mitochondrial respiration, DNA repair, and iron
      homeostasis. A steadily increasing number of disorders are being associated with
      disrupted biogenesis of Fe-S clusters. Here, we conducted whole-exome sequencing
      of patients with optic atrophy and other neurological signs of mitochondriopathy
      and identified 17 individuals from 13 unrelated families with recessive mutations
      in FDXR, encoding the mitochondrial membrane-associated flavoprotein ferrodoxin
      reductase required for electron transport from NADPH to cytochrome P450. In vitro
      enzymatic assays in patient fibroblast cells showed deficient ferredoxin NADP
      reductase activity and mitochondrial dysfunction evidenced by low oxygen
      consumption rates (OCRs), complex activities, ATP production and increased
      reactive oxygen species (ROS). Such defects were rescued by overexpression of
      wild-type FDXR. Moreover, we found that mice carrying a spontaneous mutation
      allelic to the most common mutation found in patients displayed progressive gait
      abnormalities and vision loss, in addition to biochemical defects consistent with
      the major clinical features of the disease. Taken together, these data provide
      the first demonstration that germline, hypomorphic mutations in FDXR cause a
      novel mitochondriopathy and optic atrophy in humans.

PMID- 29040576
TI  - To Everything There Is a Season: Summer-to-Winter Food Webs and the Functional
      Traits of Keystone Species.
AB  - From a trophic perspective, a seasonal increase in air temperature and
      photoperiod propagates as bottom-up pulse of primary production by plants,
      secondary production by herbivores, and tertiary production by carnivores.
      However, food web seasonality reflects not only abiotic variation in temperature
      and photoperiod, but also the composition of the biotic community and their
      functional responses to this variation. Some plants and animals-here referred to
      as seasonal specialists-decouple from food webs in winter through migration or
      various forms of metabolic arrest (e.g., senescence, diapause, and hibernation),
      whereas some plants and resident animals-here referred to as seasonal generalists
      remain present and trophically coupled in winter. The co-occurrence of species
      with divergent responses to winter introduces seasonal variation in interaction
      strengths, resulting in summer-to-winter differences in trophic organization.
      Autumn cooling and shortening day length arrests primary productivity and cues
      seasonal herbivores to decouple, leaving generalist carnivores to concentrate
      their predation on the few generalist herbivores that remain resident, active,
      and vulnerable to predation in winter, which themselves feed on the few
      generalist plant structures available in winter. Thus, what was a bottom-up
      pulse, spread among many species in summer, including highly productive seasonal
      specialists, reverses into strong top-down regulation in winter that is top
      heavy, and concentrated among a small number of generalist herbivores and their
      winter foods. Intermediate-sized, generalist herbivores that remain active and
      vulnerable to predation in winter are likely to be keystone species in seasonal
      food webs because they provide the essential ecosystem service of turning summer
      primary productivity into winter food for carnivores. Empirical examination of
      terrestrial mammals and their seasonal trophic status in the boreal forest and
      across an arctic-to-tropics seasonality gradient indicates seasonal
      specialization is more common among herbivores, small body sizes, and in regions
      with intermediate seasonality, than among carnivores, large body size, and
      regions where summers are very short or very long. Better understanding of food
      webs in seasonal environments, including their vulnerability and resilience to
      climate change, requires a multi-season perspective.

PMID- 29040577
TI  - Metabolomics of postprandial plasma alterations: a comprehensive Japanese study.
AB  - While endogenous metabolites in plasma can be used as clinical biomarkers, intra
      day variations should be carefully considered. The postprandial effect is a large
      contributing factor and is dependent on regional features (e.g. meals,
      ethnicity). Thus, for clinical application, regional-specific postprandial
      baseline data are required. In this study, 10 healthy Japanese volunteers of
      different ages and genders ate the same meal, and blood samples were taken 30 min
      before and 1 h after the meal challenge. Plasma metabolomics was conducted and
      metabolites that significantly changed with the meal challenge were extracted.
      Principal component analysis of the data from 1101 metabolites showed a
      postprandial shift with a common direction despite marked individual variation.
      Pathway enrichment analysis demonstrated known postprandial effects, including
      the energy utilization shift from lipolysis to glycolysis and the elevation of
      bile acids for lipid absorption. Other postprandial metabolic changes were
      observed, including decreases in orexigenic signals and increases of food-derived
      components. The postprandial alteration accumulated in this study will be used
      for the understanding of Japanese clinical metabolomics for health promotion in
      Japan.

PMID- 29040578
TI  - Systemic Inflammation Induced by microRNAs: Endometriosis-Derived Alterations in
      Circulating microRNA 125b-5p and Let-7b-5p Regulate Macrophage Cytokine
      Production.
AB  - Context: Endometriosis is characterized by aberrant inflammation. We previously
      reported increased levels of microRNA (miRNA) 125b-5p and decreased levels of
      miRNA Let-7b-5p in serum of patients with endometriosis. Objective: Determine the
      regulatory function of miRNAs 125b-5p and Let-7b-5p on production of
      proinflammatory cytokines in endometriosis. Design: Case-control study. Setting:
      University hospital. Patients: Women with (20) and without (26) endometriosis;
      human U937 macrophage cell line. Intervention: Sera were collected from
      surgically diagnosed patients and differentiated U937 cells that were transfected
      with miRNAs 125b-5p and Let-7b-5p mimics and inhibitor. Main Outcome Measures:
      Enzyme-linked immunosorbent assay for tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-6, IL-8, and IL-1beta levels and quantitative real-time
      polymerase chain reaction for expression of miRNAs 125b-5p and Let-7b-5p in sera
      of patients with and without endometriosis. Transfected macrophages were
      evaluated for expression of inflammatory cytokines, intracellular production, and
      secretion of these cytokines. Results: We noted substantial elevation of TNF
      alpha, IL-1beta, and IL-6, marked upregulation of miRNA 125b, and considerable
      downregulation of Let-7b in sera of patients with endometriosis vs control. There
      was a positive correlation between miRNA 125b levels and TNF-alpha, IL-1beta, and
      IL-6 and a negative correlation between miRNA Let-7b levels and TNF-alpha in sera
      of patients with endometriosis. Transfection experiments showed a noteworthy
      upregulation of TNF-alpha, IL-1beta, IL-6, and IL-8 in macrophages transfected
      with miRNA 125b mimic or Let-7b inhibitor. The secreted cytokine protein levels
      and intracellular imaging studies closely correlate with the messenger RNA
      changes. Conclusions: Endometriosis-derived miRNAs regulate macrophage cytokine
      production that contributes to inflammation associated with this condition.

PMID- 29040579
TI  - Cultural determinants influence assisted reproduction usage in Europe more than
      economic and demographic factors.
AB  - STUDY QUESTION: To what extent do financial, demographic and cultural
      determinants explain the vast cross-national differences in ART treatments in
      Europe? SUMMARY ANSWER: The normative cultural acceptance of ART is a major
      driver of ART treatments in Europe, above and beyond differences in country
      wealth, demographic aspects and religious composition. WHAT IS KNOWN ALREADY:
      There are vast differences in the number of ART treatments across European
      countries, which are to some extent related to country affluence, regulation, and
      insurance coverage and costs. The role and impact of cultural and normative
      factors has not been explored in a larger cross-national comparison. STUDY
      DESIGN, SIZE, DURATION: A descriptive and comparative cross-national analysis of
      ART treatment prevalence in over 30 European countries in 2010, with the outcome
      defined as the total number of ART cycles per million women of reproductive age
      (15-44 years). Data is drawn from multiple sources (ICMART, US Census Bureau
      Library, World Bank, Barro-Lee Educational Attainment Dataset, IFFS Surveillance
      reports, European Values Study and World Religion Database).
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Our sample includes data from 35
      European countries, where we describe the associations between demographic and
      cultural factors and the prevalence of ART treatments. Bivariate correlation and
      ordinary least squares multiple regression analysis serves to establish the
      relationships between predictor variables and the number of ART treatments per
      million women aged 15-44 years in a country. MAIN RESULTS AND THE ROLE OF CHANCE:
      A one-percent increase in national GDP is associated with 382 (95% CI: 177-587)
      additional ART procedures per million women of reproductive age, yet this effect
      is reduced to 99 (-92 to 290) treatments once cultural values and demographic
      factors are accounted for. In our fully adjusted model, normative cultural values
      measuring the acceptability of ART are the strongest predictor of ART usage, with
      a one-point increase of average approval in a country associated with 276 (167
      385) additional ART treatments per million women of reproductive age.
      LIMITATIONS, REASONS FOR CAUTION: Findings are based on a cross-sectional, cross
      national analysis, making formal tests of causality impossible and prohibiting
      inferences to the individual level. WIDER IMPLICATIONS OF THE FINDINGS: Results
      indicate that reproductive health policy should openly acknowledge the importance
      of cultural norms in informally shaping and regulating the wider availability of
      ART treatment. STUDY FUNDING/COMPETING INTEREST(S): Funding for this project was
      provided by the European Union's Seventh Framework Program (FP7 2007-2013) (No.
      320116 Families and Societies), European Research Council for the SOCIOGENOME
      Consolidator Grant (ERC-2013-CoG-615603) and the Wellcome Trust Institutional
      Strategic Support Fund (all to M.C.M.). The authors have no conflicts of interest
      to declare. TRIAL REGISTRATION NUMBER: N/A.

PMID- 29040581
TI  - Effect of school eye health promotion on children's eye health literacy in
      Vietnam.
AB  - Health promotion intervention in schools is a useful strategy to improve
      students' health awareness. The purpose of this study was to assess the effect of
      eye health promotion interventions on eye health literacy in school children in
      Vietnam. A piloted questionnaire was administered to 300 children from five
      secondary schools in Ba Ria-Vung Tau, Vietnam at baseline and re-administered
      after the eye health promotion interventions. McNemar chi-square and logistic
      regression were used for statistical analysis. A total of 300 children aged 12-15
      years (mean, 13.3 +/- 1.3 years; 60% female) participated in the baseline survey.
      The participation rate in the post-health promotion survey was 94.7%. After the
      health promotion interventions, number of children who had correct eye health
      knowledge increased by 10-20% (60-75% to 70-95%), more children reported having
      had an eye examination (63.3% to 84.7%; p < 0.001) and more reported wearing
      spectacles (36.1% to 43.4%; p = 0.04). Children in urban schools were twice as
      likely to have improved knowledge of vision loss compared with children in rural
      schools (odds ratio, 2.1-4.1; p = 0.01 to p < 0.001). Children from rural schools
      had significantly higher odds of visiting doctor after the eye problems worsened
      (odds ratio, 4.5; p < 0.001). These results imply that eye health promotion
      interventions significantly improve eye health knowledge, attitudes and practices
      of school children. Additionally, participation of parents and teachers as change
      agents may further improve children's health literacy.

PMID- 29040580
TI  - Cohort Profile: The Mother-Child Cohort in Crete, Greece (Rhea Study).

PMID- 29040582
TI  - CDC73-Related Disorders: Clinical Manifestations and Case Detection in Primary
      Hyperparathyroidism.
AB  - Context: Heterozygous pathogenic germline variants in CDC73 predispose to the
      development of primary hyperparathyroidism (pHPT) and, less frequently, ossifying
      fibroma of the jaw and renal and uterine tumors. Clinical information on CDC73
      related disorders has so far been limited to small case series. Objective: To
      assess the clinical manifestations and penetrance in CDC73-related disorders and
      to improve case detection in pHPT. Design: Nationwide retrospective Dutch cohort
      study. Setting: Tertiary referral center. Patients: We studied 89 patients with
      pHPT referred for germline CDC73 analysis and 43 subsequently tested relatives
      who proved to be mutation carriers. Investigation: Germline CDC73 mutation
      analysis. Mean Outcome: CDC73 mutation detection yield, referral rate, and CDC73
      related disease penetrance. Results: Pathogenic germline CDC73 variants were
      identified in 11 of the 89 referred pHPT patients (12.4%), with (suspected)
      hyperparathyroidism-jaw tumor (HPT-JT) syndrome (n = 3), familial isolated pHPT
      (n = 5), apparently sporadic parathyroid carcinoma (n = 2), and apparently
      sporadic parathyroid adenoma (n = 1). The estimated penetrance of CDC73-related
      disorders was 65% at age 50 years (95% confidence interval, 48% to 82%) in 43
      nonindex mutation carriers. Conclusions: Germline CDC73 analysis is recommended
      in individuals with (suspected) HPT-JT syndrome, familial isolated pHPT, atypical
      or malignant parathyroid histology, and young individuals with pHPT. These
      criteria would increase germline CDC73 mutation detection, enabling optimal
      clinical management of pHPT as well as genetic counseling and surveillance for
      family members at risk for developing CDC73-related disorders.

PMID- 29040583
TI  - Taste receptor polymorphisms and male infertility.
AB  - STUDY QUESTION: Are polymorphisms of taste receptor genes associated with male
      infertility? SUMMARY ANSWER: This study has showed the associations between three
      single nucleotide polymorphisms (SNPs) in taste receptors genes (TASR) and male
      infertility. WHAT IS KNOWN ALREADY: Recent studies showed the expression of taste
      receptors in the testis and in spermatozoa, suggesting their possible role in
      infertility. The vast genetic variability in taste genes results in a large
      degree of diversity in various human phenotypes. STUDY DESIGN, SIZE, DURATION: In
      this study, we genotyped 19 SNPs in 12 taste related genes in a total of 494
      Caucasian male patients undergoing semen evaluation at the Centre of Couple
      Sterility of the Siena University Hospital. Consecutive patients were enrolled
      during infertility investigations from October 2014 to February 2016.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Median age of the patients was 36 years
      (18-58) and 141 were smokers. Genotyping was performed using the allele-specific
      PCR. The statistical analysis was carried out using generalized linear model
      (GLM) to explore the association between age, smoking, the genetic polymorphisms
      and sperm parameters. MAIN RESULTS AND THE ROLE OF CHANCE: We observed that the
      homozygous carriers of the (G) allele of the TAS2R14-rs3741843 polymorphism
      showed a decreased sperm progressive motility compared to heterozygotes and (A)
      homozygotes (P = 0.003). Moreover, the homozygous carriers of the (T) allele of
      the TAS2R3-rs11763979 SNP showed fewer normal acrosome compared with the
      heterozygous and the homozygous carriers of the (G) allele (P = 0.002). Multiple
      comparisons correction was applied and the Bonferroni-corrected critical P-value
      was = 0.003. LIMITATIONS, REASONS FOR CAUTION: The analysis is restricted to SNPs
      within genes and to men of Caucasian ancestry. WIDER IMPLICATIONS OF THE
      FINDINGS: In silico analyses strongly point towards a functional effect of the
      two SNPs: TAS2R14-rs3741843 regulates TAS2R43 expression, a gene that is involved
      in cilia motility and therefore could influences sperm mobility; the (T) allele
      of TAS2R3-rs11763979 increases the expression of the WEE2 antisense RNA one gene
      (WEE2-AS1). According to Genotype-Tissue Expression (GTEx) project the WEE2 gene
      is expressed in the testes where presumably it has the role of down regulating
      meiotic cell division. It is plausible to hypothesize that the WEE2-AS1 increased
      expression may down regulate WEE2 which in turn can alter the natural timing of
      sperm maturation increasing the number of abnormal sperm cells. STUDY
      FUNDING/COMPETING INTEREST(S): None.

PMID- 29040584
TI  - Strategies to Advance Drug Discovery in Rare Monogenic Intellectual Disability
      Syndromes.
AB  - Some intellectual disability syndromes are caused by a mutation in a single gene
      and have been the focus of therapeutic intervention attempts, such as Fragile X
      and Rett Syndrome, albeit with limited success. The rate at which new drugs are
      discovered and tested in humans for intellectual disability is progressing at a
      relatively slow pace. This is particularly true for rare diseases where so few
      patients make high-quality clinical trials challenging. We discuss how new
      advances in human stem cell reprogramming and gene editing can facilitate
      preclinical study design and we propose new workflows for how the preclinical to
      clinical trajectory might proceed given the small number of subjects available in
      rare monogenic intellectual disability syndromes.

PMID- 29040585
TI  - Emergence of mcr-1 and carbapenemase genes in hospital sewage water in Beijing,
      China.
AB  - Objectives: This study identified and characterized mcr-1-positive
      Enterobacteriaceae (MCRPE) and carbapenemase-producing Enterobacteriaceae (CPE)
      in hospital sewage water. Methods: Influent and effluent sewage samples were
      collected from five tertiary hospitals in Beijing in December 2016. Samples were
      screened for MCRPE and CPE using antibiotic selection media. Results were
      confirmed by PCR amplification of beta-lactamase and colistin resistance (mcr-1
      and mcr-2) genes and by sequencing. Antimicrobial susceptibility testing, MLST,
      conjugation and plasmid typing and S1-nuclease-PFGE/Southern blotting were
      performed for all MCRPE and CPE isolates. Results: Nine MCRPE and 12 CPE isolates
      were obtained. All mcr-1-positive isolates (n = 9) were Escherichia coli and
      belonged to eight different STs. The blaKPC-2-positive Enterobacteriaceae
      included Klebsiella pneumoniae (n = 4), Enterobacter cloacae (n = 4) and
      Citrobacter freundii (n = 1) isolates. Two C. freundii isolates and one E.
      cloacae isolate harboured the blaNDM-1 gene. MLST analysis revealed distinct
      genetic relatedness among all ST11 K. pneumoniae but not among any other
      carbapenemase-producing isolates. Conjugation and plasmid typing confirmed that
      three MCRPE isolates harboured mcr-1 on the self-transmissible IncX4 plasmid and
      the blaNDM-1 gene on the IncX3 plasmid. The sizes of the plasmids harbouring mcr
      1, blaNDM-1 and blaKPC-2 were ~33 to ~240, ~40 to ~75 and ~30 to ~90 kb,
      respectively. Conclusions: To the best of our knowledge, this is the first report
      of mcr-1-positive E. coli and blaNDM-1-carrying E. cloacae and C. freundii in
      hospital sewage water. These findings, especially the diversity of MCRPE and K.
      pneumoniae ST11 that harbour the blaKPC-2 gene, suggest that monitoring and
      management of hospital sewage water should be enhanced.

PMID- 29040587
TI  - Does low to moderate environmental exposure to noise and air pollution influence
      preterm delivery in medium-sized cities?
AB  - Background: Preterm birth (PB) is an important predictor of childhood morbidity
      and educational performance. Beyond the known risk factors, environmental
      factors, such as air pollution and noise, have been implicated in PB. In urban
      areas, these pollutants coexist. Very few studies have examined the effects of
      multi-exposure on the pregnancy duration. The objective of this study was to
      analyse the relationship between PB and environmental chronic multi-exposure to
      noise and air pollution in medium-sized cities. Methods: A case-control study was
      conducted among women living in the city of Besancon (121 671 inhabitants) or in
      the urban unit of Dijon (243 936 inhabitants) and who delivered in a university
      hospital between 2005 and 2009. Only singleton pregnancies without associated
      pathologies were considered. Four controls were matched to each case in terms of
      the mother's age and delivery location. Residential noise and nitrogen dioxide
      (NO2) exposures were calculated at the mother's address. Conditional logistic
      regression models were applied, and sensitivity analyses were performed. Results:
      This study included 302 cases and 1204 controls. The correlation between noise
      and NO2 indices ranged from 0.41 to 0.59. No significant differences were found
      in pollutant exposure levels between cases and controls. The adjusted odds ratios
      ranged between 0.96 and 1.08. Sensitivity analysis conducted using different
      temporal and spatial exposure windows demonstrated the same results. Conclusions:
      The results are in favour of a lack of connection between preterm delivery and
      multi-exposure to noise and air pollution in medium-sized cities for pregnant
      women without underlying disease.

PMID- 29040586
TI  - Plasma Nervonic Acid Is a Potential Biomarker for Major Depressive Disorder: A
      Pilot Study.
AB  - Background: Diagnostic biomarkers of major depressive disorder, bipolar disorder,
      and schizophrenia are urgently needed, because none are currently available.
      Methods: We performed a comprehensive metabolome analysis of plasma samples from
      drug-free patients with major depressive disorder (n=9), bipolar disorder (n=6),
      schizophrenia (n=17), and matched healthy controls (n=19) (cohort 1) using liquid
      chromatography time-of-flight mass spectrometry. A significant effect of
      diagnosis was found for 2 metabolites: nervonic acid and cortisone, with nervonic
      acid being the most significantly altered. The reproducibility of the results and
      effects of psychotropic medication on nervonic acid were verified in cohort 2, an
      independent sample set of medicated patients [major depressive disorder (n=45),
      bipolar disorder (n=71), schizophrenia (n=115)], and controls (n=90) using gas
      chromatography time-of-flight mass spectrometry. Results: The increased levels of
      nervonic acid in patients with major depressive disorder compared with controls
      and patients with bipolar disorder in cohort 1 were replicated in the independent
      sample set (cohort 2). In cohort 2, plasma nervonic acid levels were also
      increased in the patients with major depressive disorder compared with the
      patients with schizophrenia. In cohort 2, nervonic acid levels were increased in
      the depressive state in patients with major depressive disorder compared with the
      levels in the remission state in patients with major depressive disorder and the
      depressive state in patients with bipolar disorder. Conclusion: These results
      suggested that plasma nervonic acid is a good candidate biomarker for the
      depressive state of major depressive disorder.

PMID- 29040588
TI  - Glyphosate Resistance and EPSPS Gene Duplication: Convergent Evolution in
      Multiple Plant Species.
AB  - One of the increasingly widespread mechanisms of resistance to the herbicide
      glyphosate is copy number variation (CNV) of the 5-enolpyruvylshikimate-3
      phosphate synthase (EPSPS) gene. EPSPS gene duplication has been reported in 8
      weed species, ranging from 3 to 5 extra copies to more than 150 extra copies. In
      the case of Palmer amaranth (Amaranthus palmeri), a section of >300 kb containing
      EPSPS and many other genes has been replicated and inserted at new loci
      throughout the genome, resulting in significant increase in total genome size.
      The replicated sequence contains several classes of mobile genetic elements
      including helitrons, raising the intriguing possibility of extra-chromosomal
      replication of the EPSPS-containing sequence. In kochia (Kochia scoparia), from 3
      to more than 10 extra EPSPS copies are arranged as a tandem gene duplication at
      one locus. In the remaining 6 weed species that exhibit EPSPS gene duplication,
      little is known about the underlying mechanisms of gene duplication or their
      entire sequence. There is mounting evidence that adaptive gene amplification is
      an important mode of evolution in the face of intense human-mediated selection
      pressure. The convergent evolution of CNVs for glyphosate resistance in weeds,
      through at least 2 different mechanisms, may be indicative of a more general
      importance for this mechanism of adaptation in plants. CNVs warrant further
      investigation across plant functional genomics for adaptation to biotic and
      abiotic stresses, particularly for adaptive evolution on rapid time scales.

PMID- 29040589
TI  - Corifollitropin alfa followed by highly purified HMG versus recombinant FSH in
      young poor ovarian responders: a multicentre randomized controlled clinical
      trial.
AB  - STUDY QUESTION: Does administration of corifollitropin alfa followed by highly
      purified (hp) HMG result in higher ongoing pregnancy rates compared with daily
      recombinant FSH (rFSH) in young poor responders? SUMMARY ANSWER: Corifollitropin
      alfa followed by hp-HMG does not increase ongoing pregnancy rates compared with
      rFSH in young poor responders, although more supernumerary cryopreserved embryos
      were obtained with corifollitropin alfa and hp-HMG. WHAT IS KNOWN ALREADY: Poor
      ovarian response remains one of the main therapeutic challenges in women
      undergoing ovarian stimulation, given that very low live birth rates of 6% have
      been reported in this particular group of infertile patients. Nevertheless,
      concerns have been raised that a degree of heterogeneity remains, as the
      prognostic effect of individual factors is still unclear, particularly for the
      young poor responder group. The rationale for conducting the current randomized
      trial was based on the results of a previous pilot study demonstrating promising
      results with the administration of hp-HMG following corifollitropin alpha in
      women younger than 40 years of age, fulfilling the 'Bologna' criteria. STUDY
      DESIGN, SIZE, DURATION: A multicenter, phase III, superiority, randomized trial
      was conducted using a parallel two-arm design. The study included 152 patients
      younger than 40 years old and fulfilling the 'Bologna' criteria for poor ovarian
      response, from one tertiary referral centre in Europe and one tertiary referral
      centre in Asia. Enrolment was performed from March 2013 to May 2016.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible patients were randomized to
      either administration of 150 MUg corifollitropin alfa followed by 300 IU hp-HMG
      (Group A) or to 300 IU of daily recombinant FSH (Group B) in a fixed GnRH
      antagonist protocol. The randomization sequence was created using a computer
      generated randomization list stratified by centre, using 1:1 allocation. The
      primary outcome was ongoing pregnancy rate (defined as the presence of an
      intrauterine gestational sac with an embryonic pole demonstrating cardiac
      activity at 9-10 weeks of gestation). Secondary outcomes included embryo
      cryopreservation rates, clinical and biochemical pregnancy rates and number of
      oocytes retrieved. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 152 poor ovarian
      responders defined by the 'Bologna' criteria were included in the study. Using an
      intention-to treat analysis, the ongoing pregnancy rates did not differ
      significantly between Group A 11/77 (14.3%) and Group B 11/70 (15.7%), absolute
      difference: -0.4 (-11.5 to 10.8), OR = 0.9 (0.4-2.4). Biochemical and clinical
      pregnancy rates, live birth rates and the number of oocytes retrieved were also
      comparable between the two groups. Nevertheless, more patients in the
      corifollitropin alfa group had cryopreserved embryos compared to the rFSH group
      [22 (28.6%) versus 10 (14.3%), OR = 2.4 (1.01-5.5)]. Incidentally, Asian patients
      had significantly lower cancellation rates compared to European poor responders
      [2/64 (3.1%) versus 17/83 (20.4%), OR = 0.12 (0.03-0.5)]. This discrepancy could
      be explained by the fact that Asian women were better prognosis patients than
      European patients, with significantly lower FSH [9.8 (5.3) versus 11.5 (5.4), P =
      0.017] and significantly higher AMH [1.1 (0.9) versus 0.4 (0.3), P-value <0.001]
      levels. LIMITATIONS, REASONS FOR CAUTION: Ongoing pregnancy rates close to 14%
      for both treatment groups differ significantly from the hypothesized primary
      outcome rates used in the power calculation. Therefore, our randomized trial
      might have been underpowered to detect smaller differences. The use of multiple
      secondary outcomes and multiple comparisons could have increased a Type 1 error.
      Finally, although the chance of selection biases remains low given the nature of
      the infertile population, the open-label design could have been a limitation.
      WIDER IMPLICATIONS OF THE FINDINGS: Poor ovarian response represents a challenge
      and although a specific protocol may have increased the number of cryopreserved
      embryos, no difference was observed in ongoing pregnancy rates. Our study, being
      one of the largest RCTs in 'Bologna' criteria poor responders, highlights that
      baseline characteristics may play a crucial role in clinical prognosis of this
      population. Given that ovarian stimulation using novel protocols does not seem to
      significantly increase pregnancy rates even in young women, we suggest that
      future clinical research should focus on increasing the number of recruitable
      follicles and on oocyte quality rather than evaluating different stimulation
      protocols. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for
      this study. P.D., N.L.V., N.A.V.H., A.V., M.T.H., M.C., A.T.L. and A.V.V. have no
      conflict of interest to report. C.B. has received unrestricted research grants
      from MSD and Ferring as well as honoraria for lectures from Abbott, MSD, Merck
      and Ferring. P.H has received unrestricted research grants from MSD, Merck and
      Ferring as well as honoraria for lectures from Merck, MSD and IBSA. H.T. has
      received unrestricted research grants from MSD, Merck, Ferring, Cook, Roche
      Diagnostics, Besins International and Goodlife as well as consultation fees for
      research project in female infertility from Merck Finox, Abbott and ObsEva.
      N.P.P. has received unrestricted research grants from MSD, Ferring, Roche
      Diagnostics and Besins International as well as honoraria for lectures from MSD,
      Merck and Ferring. TRIAL REGISTRATION NUMBER: The EUDRACT number of the trial was
      2013-000583-29 and the study was registered at clinicaltrials.gov (NCT01816321).
      TRIAL REGISTRATION DATE: 19 February 2013. DATE OF FIRST PATIENT ENROLMENT: 28
      February 2013.

PMID- 29040590
TI  - Constructing the crystal ball: how to get reliable prognostic information for the
      management of subfertile couples.
AB  - Couples in whom the results of an initial fertility workup fail to identify the
      presence of any obvious barriers to conception are diagnosed with unexplained
      subfertility. Couples who have tried to conceive for a relatively short time have
      a good chance of natural conception and thus may not benefit from immediate
      access to ART. As fertility decreases over time, the main dilemma that clinicians
      and couples face is when to abandon an expectant approach in favour of active
      treatment. Several prognostic or predictive models have been used to try to
      discriminate between couples with high and low chances of conception but have
      been unable to compare individualized chances of conception associated with ART
      relative to chances of natural conception at various time points. These models
      are also unable to recalculate the chances of pregnancy at subsequent time points
      in those who return after a period of unsuccessful expectant management. In this
      paper, we discuss currently available models. We conclude that in order to
      provide accurate, individualized and dynamic fertility prognoses associated with
      and without treatment at different points in time, we need to develop, validate
      and update clinical prediction models which are fit for purpose. We suggest
      several steps to move the field forwards.

PMID- 29040591
TI  - Revised Distribution of Bactrocera tryoni in Eastern Australia and Effect on
      Possible Incursions of Mediterranean Fruit Fly: Development of Australia's
      Eastern Trading Block.
AB  - Bactrocera tryoni (Froggatt) (Diptera: Tephritidae), commonly called 'Queensland
      fruit fly' in Australia, and Mediterranean fruit fly (Ceratitis capitata
      Wiedemann) (Diptera: Tephritidae) are the two most economically important fruit
      fly in Australia with B. tryoni in the east and Mediterranean fruit fly in the
      west. The two species coexisted for several decades, but it is believed that B.
      tryoni displaced Mediterranean fruit fly. In southeastern Australia, this was
      deemed inadequate for export market access, and a large fruit fly free zone
      (fruit fly exclusion zone) was developed in 1996 where B. tryoni was eradicated
      by each state department in their portion of the zone. This zone caused an
      artificial restricted distribution of B. tryoni. When the fruit fly exclusion
      zone was withdrawn in Victoria and New South Wales in 2013, B. tryoni became
      endemic once again in this area and the national distribution of B. tryoni
      changed. For export markets, B. tryoni is now deemed endemic to all eastern
      Australian states, except for the Greater Sunraysia Pest-Free Area. All
      regulatory controls have been removed between eastern states, except for some
      small zones, subject to domestic market access requirements. The eastern
      Australian states now form a B. tryoni endemic trading group or block. All
      Australian states and territories maintain legislation to regulate the movement
      of potentially infested host fruit into their states. In particular, eastern
      states remain active and regulate the entry of commodities possibly infested with
      Mediterranean fruit fly. The combination of regulatory controls limits the
      chances of Mediterranean fruit fly entering eastern states, and if it did,
      Mediterranean fruit fly is unlikely to establish in the opposition to a well
      established B. tryoni population.

PMID- 29040593
TI  - Oral Exposure to Paraquat Triggers Earlier Expression of Phosphorylated alpha
      Synuclein in the Enteric Nervous System of A53T Mutant Human alpha-Synuclein
      Transgenic Mice.
AB  - The misfolded alpha-synuclein protein, phosphorylated at serine 129 (pSer129
      alpha-syn), is the hallmark of Parkinson disease (PD). Detected also in the
      enteric nervous system (ENS), it supports the recent theory that PD could start
      in the gut, rather than the brain. In a previous study, using a transgenic mouse
      model of human synucleinopathies expressing the A53T mutant alpha-synuclein
      (TgM83), in which a neurodegenerative process associated with alpha-synuclein
      occurs spontaneously in the brain, we have shown earlier onset of pSer129 alpha
      syn in the ENS. Here, we used this model to study the impact of paraquat (PQ) a
      neurotoxic herbicide incriminated in PD in agricultural workers) on the enteric
      pSer129 alpha-syn expression in young mice. Orally delivered in the drinking
      water at 10 mg/kg/day for 6-8 weeks, the impact of PQ was measured in a time
      dependent manner on weight, locomotor abilities, pSer129 alpha-syn, and glial
      fibrillary acidic protein (GFAP) expression levels in the ENS. Remarkably,
      pSer129 alpha-syn was detected in ENS earlier under PQ oral exposure and enteric
      GFAP expression was also increased. These findings bring additional support to
      the theory that neurotoxic agents such as PQ initiate idiopathic PD after oral
      delivery.

PMID- 29040592
TI  - The Association Between IGF-I and IGFBP-3 and Incident Diabetes in an Older
      Population of Men and Women in the Cardiovascular Health Study.
AB  - Context: Insulin-like growth factor-I (IGF-I) has structural and functional
      similarities to insulin and may play a role in glucose homeostasis, along with
      insulin-like growth factor binding protein-3 (IGFBP-3), which binds the majority
      of circulating IGF-I. Objective: To assess whether IGF-I and IGFBP-3 are
      associated with a higher risk of incident diabetes in older adults. Design:
      Participants in the Cardiovascular Health Study (n = 3133), a cohort of adults
      aged >=65 years, were observed for 16 years (n = 3133) for the development of
      incident diabetes. Statistical models were fit separately for men and women
      because of interactions with sex (P interaction: IGF-I, 0.02; IGFBP-3, 0.009) and
      were adjusted for relevant covariates. Setting: General community. Participants:
      Older adults who were nondiabetic at baseline and who did not develop diabetes
      within the first year of follow-up. Interventions: Not applicable. Main Outcome
      Measure: Incident diabetes as measured by fasting plasma glucose (FPG) >=126
      mg/dL, non-FPG >=200 mg/dL, use of pharmacological treatment of diabetes, or
      existence of two or more inpatient or three or more outpatient or (at least one
      inpatient and at least one outpatient) Centers for Medicare & Medicaid Services
      claims with the diagnostic International Classification of Diseases, Ninth
      Revision, Clinical Modification code of 250.xx. Results: In women, higher IGFBP-3
      (hazard ratio tertile 3 vs tertile 1 = 2.30; 95% confidence interval, 1.55 to
      3.40; P trend < 0.0001) was significantly associated with incident diabetes.
      Total IGF-I was not significantly associated with incident diabetes. In men,
      neither IGF-I nor IGFBP-3 was significantly associated with incident diabetes.
      Conclusions: We confirmed a previously reported association between circulating
      IGFBP-3 and diabetes risk in the older adult population, establishing that this
      association is present among women but could not be shown to be associated in
      men.

PMID- 29040594
TI  - Association between exposure to second-hand smoke and telomere length: cross
      sectional study of 1303 non-smokers.
AB  - Background: Both active smoking and second-hand smoke (SHS) are important risk
      factors for many age-related diseases. Active smoking is associated with
      shortened telomere length. However, whether SHS accelerates telomere attrition
      with age is uncertain. The aim of this study was to examine the association
      between SHS exposure and shortening by age of leukocyte telomere length among
      adult non-smokers. Methods: We undertook a cross-sectional study of the
      association between self-reported levels of SHS exposure and telomere length
      shortening per annum on a subgroup of participants from the Scottish Family
      Health Study. Inclusion was restricted to non-smokers aged >= 18 years, who had
      provided self-reported overall usual SHS exposure (total hours per week) and
      blood samples for telomere analysis. Linear regression models were used to
      compare the ratio of telomere repeat copy number to single copy gene number
      (T/S)by age according to SHS exposure. Results: Of the 1303 eligible
      participants, 779 (59.8%) reported no SHS exposure, 495 (38.0%) low exposure (1
      19 h per week) and 29 (2.2%) high exposure (>=20 h per week). In the univariate
      linear regression analyses, relative T/S ratio declined with increasing age in
      all exposure groups. Telomere length decreased more rapidly with increasing age
      among those with high exposure to SHS [adjusted coefficient -0.019, 95%
      confidence interval (CI) -0.031- -0.007) when compared with both those with no
      exposure to SHS (adjusted coefficient -0.006, 95% CI -0.008- -0.004) (high vs no
      SHS: P = 0.010) and those with low exposure to SHS (adjusted coefficient -0.005,
      95% CI -0.007- -0.003) (high vs low SHS: P = 0.005). Conclusions: Our findings
      suggest that high SHS exposure may accelerate normal biological ageing, and
      support efforts to protect the public from SHS exposure. Further studies on
      relevant mechanisms should be conducted.

PMID- 29040595
TI  - A comparison of levofloxacin and oral third-generation cephalosporins as
      antibacterial prophylaxis in acute leukaemia patients during chemotherapy-induced
      neutropenia.
AB  - Background: There is demonstrated benefit with fluoroquinolones as infection
      prophylaxis in neutropenic patients; however, side effects, drug interactions and
      increasing resistance necessitate investigation of alternative therapies.
      Objectives: To compare the incidence of febrile neutropenia in high-risk patients
      with haematological malignancy receiving a fluoroquinolone with those receiving
      an oral third-generation cephalosporin (OTGC) as antibacterial prophylaxis during
      chemotherapy-induced neutropenia. Methods: A retrospective, matched, single
      centre study comparing clinical and microbiological outcomes in acute leukaemia
      patients receiving fluoroquinolones versus OTGCs as antibacterial prophylaxis
      after chemotherapy. Results: A total of 120 patients (levofloxacin n = 80, OTGC n
      = 40) were included and matched. The 30 day incidence of febrile neutropenia was
      89.7% (95% CI = 82.4-93.9). The rates of febrile neutropenia were similar between
      antimicrobials (OTGC versus levofloxacin HR = 0.90, 95% CI = 0.54-1.52, P =
      0.70). The most frequent site of infection was the bloodstream (line related) (n
      = 24, 62%) and the majority (n = 28, 72%) of infections were caused by Gram
      positive organisms. Groups were similar in terms of site of infection (P = 0.91)
      and morphology of recovered microorganisms (P = 0.74). There were significantly
      more cultures positive for Enterobacter spp. in the OTGC group (P = 0.043). Three
      patients died during follow-up (from first dose up to 30 days after the last
      dose) (30 day survival = 99.2%, 95% CI = 97.5-100), with only two of the reported
      deaths attributable to infection. Conclusions: These findings demonstrate
      comparable rates of febrile neutropenia and culture positivity with an increase
      in cultures positive for Enterobacter spp. when OTGCs are compared with
      levofloxacin for antibacterial prophylaxis during chemotherapy-induced
      neutropenia. Further prospective, randomized investigation is warranted.

PMID- 29040596
TI  - High-fidelity phenotyping: richness and freedom from bias.
AB  - Electronic health record phenotyping is the use of raw electronic health record
      data to assert characterizations about patients. Researchers have been doing it
      since the beginning of biomedical informatics, under different names. Phenotyping
      will benefit from an increasing focus on fidelity, both in the sense of
      increasing richness, such as measured levels, degree or severity, timing,
      probability, or conceptual relationships, and in the sense of reducing bias.
      Research agendas should shift from merely improving binary assignment to studying
      and improving richer representations. The field is actively researching new
      temporal directions and abstract representations, including deep learning. The
      field would benefit from research in nonlinear dynamics, in combining mechanistic
      models with empirical data, including data assimilation, and in topology. The
      health care process produces substantial bias, and studying that bias explicitly
      rather than treating it as merely another source of noise would facilitate
      addressing it.

PMID- 29040597
TI  - Mendelian randomization: a novel approach for the prediction of adverse drug
      events and drug repurposing opportunities.
AB  - Identification of unintended drug effects, specifically drug repurposing
      opportunities and adverse drug events, maximizes the benefit of a drug and
      protects the health of patients. However, current observational research methods
      are subject to several biases. These include confounding by indication, reverse
      causality and missing data. We propose that Mendelian randomization (MR) offers a
      novel approach for the prediction of unintended drug effects. In particular, we
      advocate the synthesis of evidence from this method and other approaches, in the
      spirit of triangulation, to improve causal inferences concerning drug effects. MR
      addresses some of the limitations associated with the existing methods in this
      field. Furthermore, it can be applied either before or after approval of the
      drug, and could therefore prevent the potentially harmful exposure of patients in
      clinical trials and beyond. The potential of MR as a pharmacovigilance and drug
      repurposing tool is yet to be realized, and could both help prevent adverse drug
      events and identify novel indications for existing drugs in the future.

PMID- 29040599
TI  - Measles Virus Is Unforgiving Where Immunity Gaps Exist.

PMID- 29040598
TI  - Effect of Metformin on Vascular Function in Children With Type 1 Diabetes: A 12
      Month Randomized Controlled Trial.
AB  - Context: Children with type 1 diabetes have vascular dysfunction preceding
      atherosclerosis. Early interventions are needed to reduce cardiovascular disease.
      Objective: To evaluate the effect of metformin on vascular function in children
      with type 1 diabetes. Design: Twelve-month double-blind, randomized, placebo
      controlled trial. Setting: Tertiary pediatric diabetes clinic. Participants:
      Ninety children (8 to 18 years of age), >50th percentile body mass index (BMI),
      with type 1 diabetes. Intervention: Metformin (up to 1 g twice a day) or placebo.
      Main Outcome Measure: Vascular function measured by brachial artery ultrasound
      [flow-mediated dilatation/glyceryl trinitrate-mediated dilatation (GTN)].
      Results: Ninety participants were enrolled [41 boys, 13.6 (2.5) years of age, 45
      per group], 10 discontinued intervention, and 1 was lost to follow-up. On
      metformin, GTN improved, independent of glycosylated hemoglobin (HbA1c), by 3.3
      percentage units [95% confidence interval (CI) 0.3, 6.3, P = 0.03] and insulin
      dose reduced by 0.2 U/kg/d (95% CI 0.1, 0.3, P = 0.001) during 12 months, with
      effects from 3 months. Metformin had a beneficial effect on HbA1c at 3 months (P
      = 0.001) and difference in adjusted HbA1c between groups during 12 months was
      1.0%; 95% CI 0.4, 1.5 (10.9 mmol/mol; 95% CI 4.4, 16.4), P = 0.001. There were no
      effects on carotid/aortic intima media thickness, BMI, lipids, blood pressure, or
      other cardiovascular risk factors. Median (95% CI) adherence, evaluated by
      electronic monitoring, was 75.5% (65.7, 81.5), without group differences. More
      gastrointestinal side effects were reported on metformin (incidence rate ratio
      1.65, 95% CI 1.08, 2.52, P = 0.02), with no difference in hypoglycemia or
      diabetic ketoacidosis. Conclusions: Metformin improved vascular smooth muscle
      function and HbA1c, and lowered insulin dose in type 1 diabetes children. These
      benefits and good safety profile warrant further consideration of its use.

PMID- 29040600
TI  - Robust inference in summary data Mendelian randomization via the zero modal
      pleiotropy assumption.
AB  - Background: Mendelian randomization (MR) is being increasingly used to strengthen
      causal inference in observational studies. Availability of summary data of
      genetic associations for a variety of phenotypes from large genome-wide
      association studies (GWAS) allows straightforward application of MR using summary
      data methods, typically in a two-sample design. In addition to the conventional
      inverse variance weighting (IVW) method, recently developed summary data MR
      methods, such as the MR-Egger and weighted median approaches, allow a relaxation
      of the instrumental variable assumptions. Methods: Here, a new method - the mode
      based estimate (MBE) - is proposed to obtain a single causal effect estimate from
      multiple genetic instruments. The MBE is consistent when the largest number of
      similar (identical in infinite samples) individual-instrument causal effect
      estimates comes from valid instruments, even if the majority of instruments are
      invalid. We evaluate the performance of the method in simulations designed to
      mimic the two-sample summary data setting, and demonstrate its use by
      investigating the causal effect of plasma lipid fractions and urate levels on
      coronary heart disease risk. Results: The MBE presented less bias and lower type
      I error rates than other methods under the null in many situations. Its power to
      detect a causal effect was smaller compared with the IVW and weighted median
      methods, but was larger than that of MR-Egger regression, with sample size
      requirements typically smaller than those available from GWAS consortia.
      Conclusions: The MBE relaxes the instrumental variable assumptions, and should be
      used in combination with other approaches in sensitivity analyses.

PMID- 29040601
TI  - Data Resource Profile: The UK Cystic Fibrosis Registry.

PMID- 29040602
TI  - Software Application Profile: PHESANT: a tool for performing automated phenome
      scans in UK Biobank.
AB  - Motivation: Epidemiological cohorts typically contain a diverse set of phenotypes
      such that automation of phenome scans is non-trivial, because they require highly
      heterogeneous models. For this reason, phenome scans have to date tended to use a
      smaller homogeneous set of phenotypes that can be analysed in a consistent
      fashion. We present PHESANT (PHEnome Scan ANalysis Tool), a software package for
      performing comprehensive phenome scans in UK Biobank. General features: PHESANT
      tests the association of a specified trait with all continuous, integer and
      categorical variables in UK Biobank, or a specified subset. PHESANT uses a novel
      rule-based algorithm to determine how to appropriately test each trait, then
      performs the analyses and produces plots and summary tables. Implementation: The
      PHESANT phenome scan is implemented in R. PHESANT includes a novel Javascript
      D3.js visualization and accompanying Java code that converts the phenome scan
      results to the required JavaScript Object Notation (JSON) format. Availability:
      PHESANT is available on GitHub at [https://github.com/MRCIEU/PHESANT]. Git tag
      v0.5 corresponds to the version presented here.

PMID- 29040603
TI  - Mitosis-specific acetylation tunes Ran effector binding for chromosome
      segregation.
AB  - Stable transmission of genetic information during cell division requires faithful
      mitotic spindle assembly and chromosome segregation. The Ran GTPase plays a key
      role in mitotic spindle assembly. However, how the generation of a chemical
      gradient of Ran-GTP at the spindle is coupled to mitotic post-translational
      modifications has never been characterized. Here, we solved the complex structure
      of Ran with the nucleotide release factor Mog1 and delineated a novel mitosis
      specific acetylation-regulated Ran-Mog1 interaction during chromosome
      segregation. Our structure-guided functional analyses revealed that Mog1 competes
      with RCC1 for Ran binding in a GTP/GDP-dependent manner. Biochemical
      characterization demonstrated that Mog1-bound Ran prevents RCC1 binding and
      subsequent GTP loading. Surprisingly, Ran is a bona fide substrate of TIP60, and
      the acetylation of Lys134 by TIP60 liberates Mog1 from Ran binding during
      mitosis. Importantly, this acetylation-elicited switch of Ran binding to RCC1
      promotes high level of Ran-GTP, which is essential for chromosome alignment.
      These results establish a previously uncharacterized regulatory mechanism in
      which TIP60 provides a homeostatic control of Ran-GTP level by tuning Ran
      effector binding for chromosome segregation in mitosis.

PMID- 29040605
TI  - Negative-Assortative Mating in the White-Throated Sparrow.
AB  - Nonrandom mating based on phenotype has been observed in a number of organisms,
      but a very high proportion of these examples are of assortative mating. The
      strongest example of negative-assortative mating is for white-striped versus tan
      striped crown in the white-throated sparrow, where about 98% of the observed
      pairings (mated pairs or social pairs) are between mates with different
      phenotypes and the correlation between mating types is -0.964. Although nonrandom
      mating has been explored theoretically for decades, these models have generally
      not focused on specific well-documented examples. Here we have developed a model
      to investigate the dynamics and equilibrium of this iconic example. The observed
      pattern of mating appears to be the result of 96% negative-assortative mating and
      a 17% advantage of W (white) male * T (tan) female matings compared to the
      reciprocal T male * W female matings. The equilibrium heterozygosity given these
      values is 0.500, very close to the 0.501 observed in our large sample of
      pairings, and this heterozygosity has been maintained for the 29 years from 1988
      to 2016. In addition, the equilibrium frequency of 2m inversion determining the
      white-striped phenotype has been maintained at a frequency very close to its
      equilibrium frequency of 0.25. Overall, this model demonstrates how evolutionary
      genetic models can be used to understand negative-assortative mating.

PMID- 29040604
TI  - Associations of Plasma Cytokine and Microbial Translocation Biomarkers With
      Immune Reconstitution Inflammatory Syndrome.
AB  - A nested case-cohort study was performed in participants of a clinical trial of
      first-line human immunodeficiency virus treatments to investigate plasma
      biomarkers of inflammation and microbial translocation for their association with
      immune reconstitution inflammatory syndrome (IRIS). Fifty-one of 1452
      participants with baseline CD4 count <350 cells/MUL developed IRIS. Plasma from
      51 IRIS cases, including 6 stratified by preenrollment CD4 count <=200 cells/MUL,
      were analyzed and compared to 94 non-IRIS controls. At baseline, CXCL10,
      lipopolysaccharide, soluble CD14, 16S ribosomal DNA, and interferon-alpha2 were
      associated with greater risk of IRIS. Systemic inflammation through persistent
      monocyte activation and microbial translocation appear to be important in IRIS
      pathogenesis.

PMID- 29040606
TI  - Pinopode score around the time of implantation is predictive of successful
      implantation following frozen embryo transfer in hormone replacement cycles.
AB  - STUDY QUESTION: Is pinopode measurement of any prognostic value? SUMMARY ANSWER:
      Pinopode expression was significantly associated with the occurrence of pregnancy
      after frozen embryo transfer. WHAT IS KNOWN ALREADY: Pinopodes are expressed in
      the endometrium during the implantation period. Pinopode measurement has been
      proposed as a marker of endometrial receptivity. STUDY DESIGN, SIZE, DURATION: A
      prospective cohort study was conducted at the Center of Reproductive Medicine,
      Sir Run Run Shaw Hospital, between 2014 and 2016, recruiting 172 women with
      infertility and undergoing frozen embryo transfer following IVF treatment. Among
      172 participants, 46 women took part in the first study to quantify the daily
      changing pattern of pinopodes 3-7 days after the initiation of progesterone
      therapy in the hormone replacement cycles and the remaining 126 women with
      infertility participated in a study to examine the relationship between pinopode
      count and pregnancy outcome following frozen embryo transfer in hormone
      replacement cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: The mean age of
      participants was 29 years old. All participants received an artificial hormone
      replacement protocol capable of supporting successful implantation. Endometrial
      biopsies from 46 women were obtained 3, 4, 5, 6 and 7 days after the initiation
      of progesterone therapy (P + 3, n = 6; P + 4, n = 6; P + 5, n = 11; P + 6, n =
      13; P + 7, n = 10, respectively). Another 126 endometrial biopsies were obtained
      precisely 6 days after the initiation of progesterone. Scanning electron
      microscopy was used to capture the pinopode images, followed by use of the image
      J program to quantify the count and subtype of the pinopodes. MAIN RESULTS AND
      THE ROLE OF CHANCE: We found that at least 60 microscopic fields were necessary
      to achieve a reproducible result. An intra-observer variability study showed good
      agreement between two measurements regarding the developing pinopode (DP) subtype
      (r = 0.95) and the fully developed pinopode (FDP) subtype (r = 0.86) but not for
      the regressing (RP) pinopode subtype (r = 0.39). The proportion of DP/total
      pinopodes (TP) declined rapidly form day P + 4 to a minimum on day P + 6. The
      percentage of FDP/TP increased rapidly from day P + 4 to reach a peak on day P +
      6. On the other hand, the percentage of RP/TP reached a peak on day P + 7.
      Participants who conceived had a significantly (P = 0.011) higher percentage of
      FDP/TP on day P + 6 and significantly (P = 0.005) lower percentage of DP/TP on
      the same day compared with participants who did not become pregnant. Using a
      scoring system incorporating the percentages of DP and FDP, it was found that the
      pregnancy rate and the embryo implantation rate of women with a high pinopode
      score (82.3%; 63.0%) was significantly (P = 0.001; P = 0.046) higher than that of
      women with a low pinopode score (53.3%; 46.7%), respectively. There remains a
      possibility that the observations could have arisen due to chance. LIMITATIONS,
      REASONS FOR CAUTION: This study examined pinopode count and subtype in the HRT
      cycles, and it is uncertain whether the same observations apply to in natural
      cycles. WIDER IMPLICATIONS OF THE FNDINGS: Pinopodes have been questioned as a
      potential marker of endometrial receptivity for many years. Our results suggested
      that pinopode measurement may be of value in predicting pregnancy. STUDY
      FUNDING/COMPETING INTEREST(S): The study was supported by the grants from the
      general project of medicine and health in Zhejiang Province of China (2015KYA142;
      2018KY106), the Key Research and Development Program of Zhejiang Province
      (2017C03022) and the National Natural Science Foundation of China (81701514).The
      funders had no role in the study design, data collection and analysis, decision
      to publish or preparation of the manuscript. We have no competing interests to
      declare. TRIAL REGISTRATION NUMBER: ISRCTN26300668.

PMID- 29040607
TI  - Data Resource Profile: Danish Heart Statistics.

PMID- 29040608
TI  - Risk factors for resistance and MDR in community urine isolates: population-level
      analysis using the NHS Scotland Infection Intelligence Platform.
AB  - Background: Urinary tract infections (UTIs) are common. Antibiotic treatment is
      usually empirical, with the risk of under-treatment of resistant infections.
      Objectives: To characterize risk factors for antibiotic-resistant community urine
      isolates using routine record-linked health data. Methods: Within the NHS
      Scotland Infection Intelligence Platform, national surveillance patient-level
      data on community urine isolates (January 2012-June 2015) were linked to hospital
      activity and community prescribing data. Associations between age, gender,
      comorbidity, care home residence, previous hospitalizations, antibiotic exposure
      and resistant (any antibiotic) or MDR (>=1 antibiotic from >=3 categories)
      urinary isolates were quantified using multivariable logistic regression.
      Results: Of 40984 isolates, 28% were susceptible, 45% were resistant and 27% were
      MDR. Exposure to >= 4 different antibiotics in the prior 6 months increased MDR
      risk (OR 6.81, 95% CI 5.73-8.11). MDR was associated with >=29 DDD cumulative
      exposure, in the prior 6 months, for any antibiotic (OR 6.54, 95% CI 5.88-7.27),
      nitrofurantoin (OR 8.56, 95% CI 6.56-11.18) and trimethoprim (OR 14.61, 95% CI
      10.53-20.27). Associations persisted for 10-12 months for nitrofurantoin (OR
      2.31, 95% CI 1.93-2.76) and trimethoprim (OR 1.81, 95% CI 1.57-2.09). Increasing
      age, comorbidity, previous hospitalization and care home residence were
      independently associated with MDR. For resistant isolates the factors were the
      same, but with weaker associations. Conclusions: To our knowledge, we have
      demonstrated, using national capability at scale, the risk of MDR in community
      urine isolates for the first time and quantified the cumulative and sustained
      impact of antibiotic exposure. These data will inform the development of decision
      support tools for UTI treatment.

PMID- 29040609
TI  - Improving patient safety and efficiency of medication reconciliation through the
      development and adoption of a computer-assisted tool with automated electronic
      integration of population-based community drug data: the RightRx project.
AB  - Background and Objective: Many countries require hospitals to implement
      medication reconciliation for accreditation, but the process is resource
      intensive, thus adherence is poor. We report on the impact of prepopulating and
      aligning community and hospital drug lists with data from population-based and
      hospital-based drug information systems to reduce workload and enhance adoption
      and use of an e-medication reconciliation application, RightRx. Methods: The
      prototype e-medical reconciliation web-based software was developed for a cluster
      randomized trial at the McGill University Health Centre. User-centered design and
      agile development processes were used to develop features intended to enhance
      adoption, safety, and efficiency. RightRx was implemented in medical and surgical
      wards, with support and training provided by unit champions and field staff. The
      time spent per professional using RightRx was measured, as well as the medication
      reconciliation completion rates in the intervention and control units during the
      first 20 months of the trial. Results: Users identified required modifications to
      the application, including the need for dose-based prescribing, the role of the
      discharge physician in prescribing community-based medication, and access to the
      rationale for medication decisions made during hospitalization. In the
      intervention units, both physicians and pharmacists were involved in discharge
      reconciliation, for 96.1% and 71.9% of patients, respectively. Medication
      reconciliation was completed for 80.7% (surgery) to 96.0% (medicine) of patients
      in the intervention units, and 0.7% (surgery) to 82.7% of patients in the control
      units. The odds of completing medication reconciliation were 9 times greater in
      the intervention compared to control units (odds ratio: 9.0, 95% confidence
      interval, 7.4-10.9, P < .0001) after adjusting for differences in patient
      characteristics. Conclusion: High rates of medication reconciliation completion
      were achieved with automated prepopulation and alignment of community and
      hospital medication lists.

PMID- 29040611
TI  - Association between pre-pregnancy overweight and obesity and children's
      neurocognitive development: a systematic review and meta-analysis of
      observational studies.
AB  - Background: Obesity and overweight during pregnancy have been negatively
      associated with fetal and offspring neurodevelopment. The aim of this systematic
      review and meta-analysis was to assess the effect of the relationship between pre
      pregnancy overweight and obesity with children's neurocognitive development.
      Methods: We systematically searched MEDLINE, EMBASE, the Cochrane Library and the
      Web of Science databases from their inception through February 2017 for follow-up
      studies comparing the relationship between pre-pregnancy weight status and
      children's cognition. The Mantel-Haenszel fixed-effects method was used to
      calculate pooled effect size (ES) values and their corresponding 95% confidence
      intervals (CIs) comparing children's neurocognitive development between pre
      pregnancy normal weight, as reference, with overweight and obesity categories.
      Results: Fifteen articles were included in the systematic review, and nine of
      them in the meta-analysis. The pooled ES values for overweight and obese mothers
      were -0.02 (95% CI: -0.05 to 0.02) and -0.06 (95% CI: -0.09 to -0.03),
      respectively. The pooled ES for the relationship between pre-gestational excess
      weight (overweight and obesity) and children's neurocognitive development was 
      0.04 (95% CI: -0.06 to -0.02). Conclusions: Pre-pregnancy obesity might have
      negative consequences on the neurocognitive development of offspring.

PMID- 29040610
TI  - The biological impact of blood pressure-associated genetic variants in the
      natriuretic peptide receptor C gene on human vascular smooth muscle.
AB  - Elevated blood pressure (BP) is a major global risk factor for cardiovascular
      disease. Genome-wide association studies have identified several genetic variants
      at the NPR3 locus associated with BP, but the functional impact of these variants
      remains to be determined. Here we confirmed, by a genome-wide association study
      within UK Biobank, the existence of two independent BP-related signals within
      NPR3 locus. Using human primary vascular smooth muscle cells (VSMCs) and
      endothelial cells (ECs) from different individuals, we found that the BP
      elevating alleles within one linkage disequilibrium block identified by the
      sentinel variant rs1173771 was associated with lower endogenous NPR3 mRNA and
      protein levels in VSMCs, together with reduced levels in open chromatin and
      nuclear protein binding. The BP-elevating alleles also increased VSMC
      proliferation, angiotensin II-induced calcium flux and cell contraction. However,
      an analogous genotype-dependent association was not observed in vascular ECs. Our
      study identifies novel, putative mechanisms for BP-associated variants at the
      NPR3 locus to elevate BP, further strengthening the case for targeting NPR-C as a
      therapeutic approach for hypertension and cardiovascular disease prevention.

PMID- 29040612
TI  - ER stress-induced aggresome trafficking of HtrA1 protects against proteotoxicity.

PMID- 29040614
TI  - Commentary: Multistage carcinogenesis and epidemiological studies of cancer.

PMID- 29040613
TI  - DNA Data Bank of Japan: 30th anniversary.
AB  - The DNA Data Bank of Japan (DDBJ) Center (http://www.ddbj.nig.ac.jp) has been
      providing public data services for 30 years since 1987. We are collecting
      nucleotide sequence data and associated biological information from researchers
      as a member of the International Nucleotide Sequence Database Collaboration
      (INSDC), in collaboration with the US National Center for Biotechnology
      Information and the European Bioinformatics Institute. The DDBJ Center also
      services the Japanese Genotype-phenotype Archive (JGA) with the National
      Bioscience Database Center to collect genotype and phenotype data of human
      individuals. Here, we outline our database activities for INSDC and JGA over the
      past year, and introduce submission, retrieval and analysis services running on
      our supercomputer system and their recent developments. Furthermore, we highlight
      our responses to the amended Japanese rules for the protection of personal
      information and the launch of the DDBJ Group Cloud service for sharing pre
      publication data among research groups.

PMID- 29040616
TI  - Description of Evandromyia piperiformis sp. nov. (Diptera: Psychodidae).
AB  - Brazil presents great sand fly species diversity, with new species constantly
      being described, as new areas are surveyed to monitor sand flies. In captures
      undertaken in Porto Velho, Rondonia state-Brazil, a new species, Evandromyia
      (Aldamyia) piperiformissp. nov. (Godoy, Cunha & Galati 2017), was found and is
      here described. Both sexes of this new species may be distinguished from those of
      the Aldamyia subgenus through morphometric and morphological characters. Further,
      we present an identification key for the subgenus Aldamyia.

PMID- 29040615
TI  - Exploring Cascading Effects of Multimodal Communication Skills in Infants With
      Hearing Loss.
AB  - Infants and toddlers with hearing loss (HL) are at risk for developing
      communicative delays that can have a substantial lasting effect. Understanding
      child characteristics that may be targeted in early intervention is essential to
      maximizing communicative outcomes in children with HL. Among the most malleable
      predictors of communication skills include maternal responsivity, gestures, and
      vocalizations. The purpose of this study was to examine the relationship among
      maternal responsivity, prelinguistic communication skills and expressive
      vocabulary in children with HL. Based upon the results we propose a theoretical
      cascading model of communicative outcomes for children with HL such that gesture
      use may be associated with future vocalizations which may in turn be related to
      long-term spoken language outcomes. This exploratory model may be supported by
      the underlying transactional model of bidirectional language development that
      occurs through maternal sensitivity in the first two years of life. Additionally,
      parents of children with HL may be less likely to respond to a single mode of
      communication than to a combination of modes. This exploratory study provides a
      theoretical framework by which multimodal communication development in infants
      and toddlers with HL may be better understood, and suggests hypotheses for future
      research and implications for intervention practice.

PMID- 29040617
TI  - Effect of Mahanarva fimbriolata (Hemiptera: Cercopidae) Attack on Photosynthetic
      Parameters of Sugarcane Genotypes of Contrasting Susceptibility.
AB  - The aim of this study was to compare the effect of spittlebug Mahanarva
      fimbriolata Stal (Hemiptera: Cercopidae) on photosynthetic parameters of both a
      susceptible (SP81-3250) and a resistant (H.Kawandang) sugarcane genotype. In the
      first assay, the susceptibility level of genotypes to spittlebug was confirmed by
      comparing damage score and chlorophyll content of the plants. In the second
      assay, the effect of spittlebug nymphs on photosynthetic characteristics was
      assessed using the following parameters: Net photosynthetic rate (A),
      carboxylation efficiency (A/Ci), stomata conductance (gS), transpiration (E),
      electron transport rate (ETR), maximum quantum yield of Photosystem 2 (PSII)
      (FV/FM), effective quantum yield (Y(II)), photochemical quenching (Y(NPQ)), and
      nonphotochemical quenching (Y(NO)). Spittlebug nymphs affected the photosynthetic
      process of the susceptible genotype SP81-3250 by decreasing the Chl content, ETR,
      FV/FM, and Y(II). However, this genotype was able to maintain A probably due to
      its ability to maintain stomata aperture, increase the carboxylation efficiency
      of Rubisco, and dissipate excess energy through the xanthophyll cycle, as Y(NPQ)
      increased under the spittlebug attack. On the other hand, the spittlebug did not
      affect Chl content and FV/FM of the H.Kawandang genotype. Furthermore,
      H.Kawandang increased A to compensate for the sink demand by the spittlebug by
      increasing stomatal aperture and carboxylation efficiency and increasing
      efficiency of the photochemical apparatus in converting light energy into
      chemical products. We can conclude that the feeding habits of spittlebug nymphs
      have different impacts on photosynthesis of susceptible and resistant sugarcane
      genotypes.

PMID- 29040618
TI  - Securing systems leadership by local government through health and wellbeing
      strategies.
AB  - Background: The aim of this study was to strengthen Health and Wellbeing
      Strategies (HWSs) by identifying potential areas for system leadership across
      local authorities in relation to specific aspects of health/illness, wider
      determinants of health and transformational change management. Method: The work
      involved a document analysis of strengths of the first 12 HWSs produced in the
      North East of England applying principles of appreciative inquiry (AI), followed
      by a knowledge-to-action group approach with stakeholders. A summative event
      resulted in Health and Wellbeing Board (HWB) members identifying potential areas
      for collaboration. Results: The study identified diverse examples of good
      practice, and considerable consensus in terms of key priorities, both wider
      determinants such as employment, transport and housing, and subject areas such as
      lifestyle issues and children having the best start in life. There was agreement
      in principle to work across local authority boundaries, with academic partners.
      Consideration of HWSs as part of a complex adaptive system was welcomed by HWB
      Members. Conclusions: Collaborative working across HWBs could strengthen the
      effectiveness of HWSs in relation to inequalities in health, place-shaping and
      wider determinants of wellbeing. The co-production of identified areas to work
      toward health improvement was successful.

PMID- 29040619
TI  - Sublethal Effects of the Neonicotinoid Insecticide Thiamethoxam on the
      Transcriptome of the Honey Bees (Hymenoptera: Apidae).
AB  - Neonicotinoid insecticides are now the most widely used insecticides in the
      world. Previous studies have indicated that sublethal doses of neonicotinoids
      impair learning, memory capacity, foraging, and immunocompetence in honey bees
      (Apis mellifera, Linnaeus) (Hymenoptera: Apidae). Despite these, few studies have
      been carried out on the molecular effects of neonicotinoids. In this study, we
      focus on the second-generation neonicotinoid thiamethoxam, which is currently
      widely used in agriculture to protect crops. Using high-throughput RNA-Seq, we
      investigated the transcriptome profile of honey bees after subchronic exposure to
      10 ppb thiamethoxam over 10 d. In total, 609 differentially expressed genes
      (DEGs) were identified, of which 225 were upregulated and 384 were downregulated.
      Several genes, including vitellogenin, CSP3, defensin-1, Mrjp1, and Cyp6as5 were
      selected and further validated using real-time quantitative polymerase chain
      reaction assays. The functions of some DEGs were identified, and Gene Ontology
      enrichment analysis showed that the enriched DEGs were mainly linked to
      metabolism, biosynthesis, and translation. Kyoto Encyclopedia of Genes and
      Genomes pathway analysis showed that thiamethoxam affected biological processes
      including ribosomes, the oxidative phosphorylation pathway, tyrosine metabolism
      pathway, pentose and glucuronate interconversions, and drug metabolism. Overall,
      our results provide a basis for understanding the molecular mechanisms of the
      complex interactions between neonicotinoid insecticides and honey bees.

PMID- 29040620
TI  - Fitness of Mass-Reared Males of Anastrepha obliqua (Diptera: Tephritidae)
      Resulting From Mating Competition Tests in Field Cages.
AB  - The sterile insect technique uses males that have been mass-reared in a
      controlled environment. The insects, once released in the field, must compete to
      mate. However, the mass-rearing condition supposes a loss of fitness that will be
      noticeable by wild females. To compare the fitness of wild males and mass-reared
      males, three competition settings were established. In setting 1, wild males,
      mass-reared males and wild females were released in field cages. In setting 2,
      wild females and wild males were released without competition, and in setting 3,
      mass-reared males and mass-reared females were also released without competition.
      Male fitness was based on their mating success, fecundity, weight and longevity.
      The fitness of the females was measured based on weight and several demographic
      parameters. The highest percentage of mating was between wild males and wild
      females between 0800 and 0900 h in the competition condition, while the mass
      reared males started one hour later. The successful wild males weighed more and
      showed longer mating times, greater longevity and a higher number of matings than
      the mass-reared males. Although the mass-reared males showed the lowest
      percentage of matings, their fecundity when mating with wild females indicated a
      high fitness. Since the survival and fecundity of wild females that mated with
      mass-reared males decreased to become similar to those of mass-reared females
      that mated with mass-reared males, females seem to be influenced by the type of
      male (wild or mass-reared).

PMID- 29040621
TI  - Current Status of Point-of-Care Testing for Human Immunodeficiency Virus Drug
      Resistance.
AB  - Healthcare delivery has advanced due to the implementation of point-of-care
      testing, which is often performed within minutes to hours in minimally equipped
      laboratories or at home. Technologic advances are leading to point-of-care kits
      that incorporate nucleic acid-based assays, including polymerase chain reaction,
      isothermal amplification, ligation, and hybridization reactions. As a limited
      number of single-nucleotide polymorphisms are associated with clinically
      significant human immunodeficiency virus (HIV) drug resistance, assays to detect
      these mutations have been developed. Early versions of these assays have been
      used in research. This review summarizes the principles underlying each assay and
      discusses strategic needs for their incorporation into the management of HIV
      infection.

PMID- 29040622
TI  - Neurokinin B Regulates Gonadotropin Secretion, Ovarian Follicle Growth, and the
      Timing of Ovulation in Healthy Women.
AB  - Context: Neurokinin B (NKB) is obligate for human puberty, but its role in adult
      female gonadotropin secretion and ovarian follicle growth is unknown. Objective:
      To investigate antagonism of NKB on pulsatile gonadotropin-releasing hormone
      (GnRH) and luteinizing hormone (LH) secretion and ovarian follicle development in
      healthy women. Design: Open investigation of the effects of a neurokinin-3
      receptor (NK3R) antagonist (NK3Ra) vs a no-treatment control cycle. Setting:
      Clinical research facility. Patients or other participants: Healthy women with
      regular menses (n = 13). Intervention(s): NK3Ra MLE4901 40 mg taken orally twice
      daily from cycle day 5 to 6 for 7 days. Main outcome measure(s): LH secretion,
      ovarian follicle growth, and timing of ovulation. Results: NK3Ra administration
      reduced basal LH secretion without a change in pulse frequency and delayed the LH
      surge by 7 days, the duration of treatment [mean cycle day +/- standard error of
      the mean (SEM), 22 +/- 1 days vs 15 +/- 1 days in control cycles; P = 0.0006].
      Follicle growth (mean diameter at the end of administration of NK3Ra
      administration +/- SEM, 9.3 +/- 0.4 mm vs 15.1 +/- 0.9 mm in control cycles; P <
      0.0001) and rising estradiol concentrations (mean +/- SEM, 166 +/- 29 pmol/L vs
      446 +/- 86 pmol/L in control cycles; P < 0.0001) were prevented. After treatment,
      follicle development resumed and normal preovulatory follicle diameter and
      estradiol concentrations were demonstrated. Postovulatory progesterone rise was
      similarly delayed (peak cycle day, 30 +/- 2 vs 22 +/- 1; P = 0.002) and cycle
      length was prolonged (35 +/- 1 days vs 29 +/- 1 days in control cycles; P =
      0.0003) but luteal progesterone excretion was unaffected by the NK3Ra (LH surge
      day +7 mean urinary progesterone levels +/- SEM, 58 +/- 10 pmol/mol vs 48+/-7
      pmol/mol creatinine in control cycles; nonsignificant). Conclusion: These data
      demonstrate the involvement of NKB-NK3R signaling in the physiological regulation
      of GnRH/LH secretion, determining normal follicle development in women.

PMID- 29040624
TI  - Altering Practices to Include Bimodal-bilingual (ASL-Spoken English) Programming
      at a Small School for the Deaf in Canada.
AB  - Bimodal-bilingual programs are emerging as one way to meet broader needs and
      provide expanded language, educational and social-emotional opportunities for
      students who are deaf and hard of hearing (Marschark, M., Tang, G. & Knoors, H.
      (Eds). (2014). Bilingualism and bilingual Deaf education. New York, NY: Oxford
      University Press; Paludneviciene & Harris, R. (2011). Impact of cochlear implants
      on the deaf community. In Paludneviciene, R. & Leigh, I. (Eds.), Cochlear
      implants evolving perspectives (pp. 3-19). Washington, DC: Gallaudet University
      Press). However, there is limited research on students' spoken language
      development, signed language growth, academic outcomes or the social-emotional
      factors associated with these programs (Marschark, M., Tang, G. & Knoors, H.
      (Eds). (2014). Bilingualism and bilingual Deaf education. New York, NY: Oxford
      University Press; Nussbaum, D & Scott, S. (2011). The cochlear implant education
      center: Perspectives on effective educational practices. In Paludneviciene, R. &
      Leigh, I. (Eds.) Cochlear implants evolving perspectives (pp. 175-205).
      Washington, DC: Gallaudet University Press. The cochlear implant education
      center: Perspectives on effective educational practices. In Paludnevicience &
      Leigh (Eds). Cochlear implants evolving perspectives (pp. 175-205). Washington,
      DC: Gallaudet University Press; Spencer, P. & Marschark, M. (Eds.) (2010).
      Evidence-based practice in educating deaf and hard-of-hearing students. New York,
      NY: Oxford University Press). The purpose of this case study was to look at
      formal and informal student outcomes as well as staff and parent perceptions
      during the first 3 years of implementing a bimodal-bilingual (ASL and spoken
      English) program within an ASL milieu at a small school for the deaf. Speech and
      language assessment results for five students were analyzed over a 3-year period
      and indicated that the students made significant positive gains in all areas,
      although results were variable. Staff and parent survey responses indicated
      primarily positive perceptions of the program. Some staff identified ongoing
      challenges with balancing signed and spoken language use. Many parents responded
      with strong emotions, some stating that the program was "life-changing" for their
      children/families.

PMID- 29040623
TI  - Socio-economic trajectories and cardiovascular disease mortality in older people:
      the English Longitudinal Study of Ageing.
AB  - Background: Socio-economic status from early life has been linked to
      cardiovascular disease risk, but the impact of life-course socio-economic
      trajectories, as well as the mechanisms underlying social inequalities in
      cardiovascular disease risk, is uncertain. Objectives: We assessed the role of
      behavioural, psychosocial and physiological (including inflammatory) factors in
      the association between life-course socio-economic status and cardiovascular
      disease mortality in older adults. Methods: Participants were 7846 individuals
      (44% women) from the English Longitudinal Study of Ageing, a representative study
      of individuals aged >= 50 years, established in 2002-03. Comprising four
      indicators of socio-economic status (father's social class, own education,
      occupational position and wealth), we computed an index of socio-economic
      trajectory and a lifetime cumulative socio-economic score. Behavioural (smoking,
      physical activity, alcohol consumption, body mass index) and psychosocial (social
      relations, loneliness) factors, physiological (blood pressure, total cholesterol,
      triglycerides) and inflammatory markers (C-reactive protein, fibrinogen),
      measured repeatedly over time, were potential explanatory variables.
      Cardiovascular disease mortality was ascertained by linkage of study members to a
      national mortality register. Mediation was calculated using the traditional
      'change-in-estimate method' and alternative approaches such as counterfactual
      mediation modelling could not be applied in this context. Results: During the 8.4
      year follow-up, 1301 study members died (438 from cardiovascular disease). A
      stable low-social-class trajectory was associated with around double the risk of
      cardiovascular disease mortality (hazard ratio; 95% confidence interval: 1.94,
      1.37; 2.75) compared with a stable high social class across the life course.
      Individuals in the lowest relative to the highest life-course cumulative socio
      economic status group were also more than twice as likely to die of
      cardiovascular disease (2.57, 1.81; 3.65). Behavioural factors and inflammatory
      markers contributed most to explaining this gradient, whereas the role of
      psychosocial and other physiological risk factors was modest. Conclusions: In a
      population-based cohort of older individuals living in England, we provide
      evidence that disadvantage across the life course is linked to cardiovascular
      mortality. That behavioural factors and inflammatory markers partially explain
      this gradient may provide insights into the potential for intervention.

PMID- 29040625
TI  - RISE: a database of RNA interactome from sequencing experiments.
AB  - We present RISE (http://rise.zhanglab.net), a database of RNA Interactome from
      Sequencing Experiments. RNA-RNA interactions (RRIs) are essential for RNA
      regulation and function. RISE provides a comprehensive collection of RRIs that
      mainly come from recent transcriptome-wide sequencing-based experiments like
      PARIS, SPLASH, LIGR-seq, and MARIO, as well as targeted studies like RIA-seq, RAP
      RNA and CLASH. It also includes interactions aggregated from other primary
      databases and publications. The RISE database currently contains 328,811 RNA-RNA
      interactions mainly in human, mouse and yeast. While most existing RNA databases
      mainly contain interactions of miRNA targeting, notably, more than half of the
      RRIs in RISE are among mRNA and long non-coding RNAs. We compared different RRI
      datasets in RISE and found limited overlaps in interactions resolved by different
      techniques and in different cell lines. It may suggest technology preference and
      also dynamic natures of RRIs. We also analyzed the basic features of the human
      and mouse RRI networks and found that they tend to be scale-free, small-world,
      hierarchical and modular. The analysis may nominate important RNAs or RRIs for
      further investigation. Finally, RISE provides a Circos plot and several table
      views for integrative visualization, with extensive molecular and functional
      annotations to facilitate exploration of biological functions for any RRI of
      interest.

PMID- 29040627
TI  - Risk Factors for Measles Virus Infection Among Adults During a Large Outbreak in
      Postelimination Era in Mongolia, 2015.
AB  - Background: In 2015, a large nationwide measles outbreak occurred in Mongolia,
      with very high incidence in the capital city of Ulaanbaatar and among young
      adults. Methods: We conducted an outbreak investigation including a matched case
      control study of risk factors for laboratory-confirmed measles among young adults
      living in Ulaanbaatar. Young adults with laboratory-confirmed measles, living in
      the capital city of Ulaanbaatar, were matched with 2-3 neighborhood controls.
      Conditional logistic regression was used to estimate adjusted matched odds ratios
      (aMORs) for risk factors, with 95% confidence intervals. Results: During March 1
      September 30, 2015, 20 077 suspected measles cases were reported; 14 010 cases
      were confirmed. Independent risk factors for measles included being unvaccinated
      (adjusted matched odds ratio [aMOR] 2.0, P < .01), being a high school graduate
      without college education (aMOR 2.6, P < .01), remaining in Ulaanbaatar during
      the outbreak (aMOR 2.5, P < .01), exposure to an inpatient healthcare facility
      (aMOR 4.5 P < .01), and being born outside of Ulaanbaatar (aMOR 1.8, P = .02).
      Conclusions: This large, nationwide outbreak shortly after verification of
      elimination had high incidence among young adults, particularly those born
      outside the national capital. In addition, findings indicated that nosocomial
      transmission within health facilities helped amplify the outbreak.

PMID- 29040626
TI  - A dose-response meta-analysis of chronic arsenic exposure and incident
      cardiovascular disease.
AB  - Background: Consistent evidence at high levels of water arsenic (>=100 ug/l), and
      growing evidence at low-moderate levels (<100 ug/l), support a link with
      cardiovascular disease (CVD). The shape of the dose-response across low-moderate
      and high levels of arsenic in drinking water is uncertain and critical for risk
      assessment. Methods: We conducted a systematic review of general population
      epidemiological studies of arsenic and incident clinical CVD (all CVD, coronary
      heart disease (CHD) and stroke) with three or more exposure categories. In a dose
      response meta-analysis, we estimated the pooled association between log
      transformed water arsenic (log-linear) and restricted cubic splines of log
      transformed water arsenic (non-linear) and the relative risk of each CVD
      endpoint. Results: Twelve studies (pooled N = 408 945) conducted at high (N = 7)
      and low-moderate (N = 5) levels of water arsenic met inclusion criteria, and 11
      studies were included in the meta-analysis. Compared with 10 ug/l, the estimated
      pooled relative risks [95% confidence interval (CI)] for 20 ug/l water arsenic,
      based on a log-linear model, were 1.09 (1.03, 1.14) (N = 2) for CVD incidence,
      1.07 (1.01, 1.14) (N = 6) for CVD mortality, 1.11 (1.05, 1.17) (N = 4) for CHD
      incidence, 1.16 (1.07, 1.26) (N = 6) for CHD mortality, 1.08 (0.99, 1.17) (N = 2)
      for stroke incidence and 1.06 (0.93, 1.20) (N = 6) for stroke mortality. We found
      no evidence of non-linearity, although these tests had low statistical power.
      Conclusions: Although limited by the small number of studies, this analysis
      supports quantitatively including CVD in inorganic arsenic risk assessment, and
      strengthens the evidence for an association between arsenic and CVD across low
      moderate to high levels.

PMID- 29040628
TI  - Genetic relationships between spring emergence, canopy phenology, and biomass
      yield increase the accuracy of genomic prediction in Miscanthus.
AB  - Miscanthus has potential as a bioenergy crop but the rapid development of high
      yielding varieties is challenging. Previous studies have suggested that phenology
      and canopy height are important determinants of biomass yield. Furthermore, while
      genome-wide prediction was effective for a broad range of traits, the predictive
      ability for yield was very low. We therefore developed models clarifying the
      genetic associations between spring emergence, consequent canopy phenology and
      dry biomass yield. The timing of emergence was a moderately strong predictor of
      early-season elongation growth (genetic correlation >0.5), but less so for growth
      later in the season and for the final yield (genetic correlation <0.1). In
      contrast, early-season canopy height was consistently more informative than
      emergence for predicting biomass yield across datasets for two species in
      Miscanthus and two growing seasons. We used the associations uncovered through
      these models to develop selection indices that are expected to increase the
      response to selection for yield by as much as 21% and improve the performance of
      genome-wide prediction by an order of magnitude. This multivariate approach could
      have an immediate impact in operational breeding programmes, as well as enable
      the integration of crop growth models and genome-wide prediction.

PMID- 29040629
TI  - Elongation Factor-1alpha Accurately Reconstructs Relationships Amongst Psyllid
      Families (Hemiptera: Psylloidea), with Possible Diagnostic Implications.
AB  - The superfamily Psylloidea (Hemiptera: Sternorrhyncha) lacks a robust multigene
      phylogeny. This impedes our understanding of the evolution of this group of
      insects and, consequently, an accurate identification of individuals, of their
      plant host associations, and their roles as vectors of economically important
      plant pathogens. The conserved nuclear gene elongation factor-1 alpha (EF-1alpha)
      has been valuable as a higher-level phylogenetic marker in insects and it has
      also been widely used to investigate the evolution of intron/exon structure. To
      explore evolutionary relationships among Psylloidea, polymerase chain reaction
      amplification and nucleotide sequencing of a 250-bp EF-1alpha gene fragment was
      applied to psyllids belonging to five different families. Introns were detected
      in three individuals belonging to two families. The nine genera belonging to the
      family Aphalaridae all lacked introns, highlighting the possibility of using
      intron presence/absence as a diagnostic tool at a family level. When paired with
      cytochrome oxidase I gene sequences, the 250 bp EF-1alpha sequence appeared to be
      a very promising higher-level phylogenetic marker for psyllids.

PMID- 29040631
TI  - Longevity, Fertility and Fecundity of Adult Blow Flies (Diptera: Calliphoridae)
      Held at Varying Densities: Implications for Use in Bioconversion of Waste.
AB  - Large numbers of flies are needed to produce the quantity of larvae required for
      insect bioconversion of waste. However, this 'mass-rearing' may negatively affect
      adult survival and reproductive output. This study assessed the suitability for
      mass-rearing of four blow fly species, Chrysomya chloropyga, Chrysomya chloropyga
      (Wiedemann), Chrysomya megacephala (F.), Chrysomya putoria (Wiedemann) and
      Lucilia sericata (Meigen). Flies were kept at densities of 20, 50, 100, 250, 500,
      and 1,000 flies per 30 * 30 * 30 cm cage with an even sex ratio. Time to 50%
      mortality (LT50) was recorded, and the effects of density, species, and sex on
      LT50, fecundity, and fertility were determined. Females survived longer than
      males across all species. There was evidence for a trade-off between survival and
      high fecundity in L. sericata and C. chloropyga at density 250. C. megacephala
      had low fecundity across all densities. At high densities, C. putoria had the
      lowest mortality and highest fecundity, making it the most suitable for mass
      rearing.

PMID- 29040630
TI  - Assessment of beta Cell Mass and Function by AIRmax and Intravenous Glucose in
      High-Risk Subjects for Type 1 Diabetes.
AB  - Context: There is little information regarding beta cell mass in individuals at
      early stages of type 1 diabetes (T1D). Objective: To investigate both acute
      insulin response to arginine at hyperglycemia (AIRmax), as a correlate of beta
      cell mass, and beta cell function by the intravenous glucose tolerance test
      (IVGTT) in subjects at early stages of T1D. Design/Setting/Participants: Forty
      subjects were enrolled: (1) low-risk group: relatives of patients with T1D with 0
      to 1 antibody (n = 21) and (2) high-risk group: relatives with >=2 antibodies (n
      = 19). Main Outcome Measure: Acute insulin and C-peptide responses to IVGTT and
      to AIRmax. Participants underwent two IVGTT and AIRmax procedures on different
      days. Results: AIRmax was reproducible, well tolerated, and correlated to first
      phase insulin response (FPIR) from IVGTT (r = 0.779). The high-risk group had
      greater impaired beta cell function compared with the low-risk group, determined
      both by lower mean FPIR and a greater number of subjects below an established
      threshold for abnormal function [10 of 19 (52.6%) versus 4 of 21 (19%)]. There
      was a heterogeneous AIRmax response in these subjects with low FPIR, ranging from
      38 to 250 MUU/mL. Conclusions: There is significant variation in insulin
      secretory reserve as assessed by AIRmax in family members with low beta cell
      function assessed by FPIR. As AIRmax is a functional measure of beta cell mass,
      these data suggest heterogeneity in disease pathogenesis in which mass is
      preserved in relation to function in some individuals. The tolerability and
      reproducibility of AIRmax suggest it could be a useful stratification measure in
      clinical trials of disease-modifying therapy.

PMID- 29040632
TI  - Cohort Profile: The Madagascar Health and Environmental Research (MAHERY) study
      in north-eastern Madagascar.

PMID- 29040633
TI  - Prevalence of Pre-antiretroviral-Treatment Drug Resistance by Gender, Age, and
      Other Factors in HIV-Infected Individuals Initiating Therapy in Kenya, 2013-2014.
AB  - Background: Pre-antiretroviral-treatment drug resistance (PDR) is a predictor of
      human immunodeficiency virus (HIV) treatment failure. We determined PDR
      prevalence and correlates in a Kenyan cohort. Methods: We conducted a cross
      sectional analysis of antiretroviral (ARV) treatment-eligible HIV-infected
      participants. PDR was defined as >=2% mutant frequency in a participant's HIV
      quasispecies at pol codons K103N, Y181C, G190A, M184 V, or K65R by
      oligonucleotide ligation assay and Illumina sequencing. PDR prevalence was
      calculated by demographics and codon, stratifying by prior ARV experience.
      Poisson regression was used to estimate prevalence ratios. Results: PDR
      prevalences (95% confidence interval [CI]) in 815 ARV-naive adults, 136 ARV
      experienced adults, and 36 predominantly ARV-naive children were 9.4% (7.5%
      11.7%), 12.5% (7.5%-19.3%), and 2.8% (0.1%-14.5%), respectively. Median mutant
      frequency within an individual's HIV quasispecies was 67%. PDR prevalence in ARV
      naive women 18-24 years old was 21.9% (9.3%-40.0%). Only age in females
      associated with PDR: A 5-year age decrease was associated with adjusted PDR
      prevalence ratio 1.20 (95% CI, 1.06-1.36; P = .004). Conclusions: The high PDR
      prevalence may warrant resistance testing and/or alternative ARVs in high HIV
      prevalence settings, with attention to young women, likely to have recent
      infection and higher rates of resistance. Clinical Trials Registration:
      NCT01898754.

PMID- 29040634
TI  - Implementation of acute care patient portals: recommendations on utility and use
      from six early adopters.
AB  - Objective: To provide recommendations on how to most effectively implement
      advanced features of acute care patient portals, including: (1) patient-provider
      communication, (2) care plan information, (3) clinical data viewing, (4) patient
      education, (5) patient safety, (6) caregiver access, and (7) hospital amenities.
      Recommendations: We summarize the experiences of 6 organizations that have
      implemented acute care portals, representing a variety of settings and
      technologies. We discuss the considerations for and challenges of incorporating
      various features into an acute care patient portal, and extract the lessons
      learned from each institution's experience. We recommend that stakeholders in
      acute care patient portals should: (1) consider the benefits and challenges of
      generic and structured electronic care team messaging; (2) examine strategies to
      provide rich care plan information, such as daily schedule, problem list, care
      goals, discharge criteria, and post-hospitalization care plan; (3) offer
      increasingly comprehensive access to clinical data and medical record
      information; (4) develop alternative strategies for patient education that go
      beyond infobuttons; (5) focus on improving patient safety through explicit safety
      oriented features; (6) consider strategies to engage patient caregivers through
      portals while remaining cognizant of potential Health Insurance Portability and
      Accountability Act (HIPAA) violations; (7) consider offering amenities to
      patients through acute care portals, such as information about navigating the
      hospital or electronic food ordering.

PMID- 29040635
TI  - Ceftazidime/avibactam use for carbapenem-resistant Klebsiella pneumoniae
      meningitis: a case report.

PMID- 29040637
TI  - In Reply: Simple Preoperative Patient-Reported Factors Predict Adverse Outcome
      After Elective Cranial Neurosurgery.

PMID- 29040636
TI  - VT-1161 protects mice against oropharyngeal candidiasis caused by fluconazole
      susceptible and -resistant Candida albicans.
AB  - Background: Candida albicans, the most common human fungal pathogen, causes
      chronic mucosal infections in patients with inborn errors of IL-17 immunity that
      rely heavily on chronic, often lifelong, azole antifungal agents for treatment.
      However, a rise in azole resistance has predicated a need for developing new
      antifungal drugs. Objectives: To test the in vitro and in vivo efficacy of VT
      1161 and VT-1129 in the treatment of oropharyngeal candidiasis with azole
      susceptible or -resistant C. albicans strains. Methods: MICs of VT-1161, VT-1129
      and nine licensed antifungal drugs were determined for 31 Candida clinical
      isolates. The drug concentrations in mouse serum and tongues were measured
      following oral administration. IL-17-signalling-deficient Act1-/- mice were
      infected with fluconazole-susceptible or fluconazole-resistant C. albicans
      strains, and the amount of mucosal fungal burden was determined after fluconazole
      or VT-1161 treatment. Results: Fourteen isolates (45%) were not fluconazole
      susceptible (MIC >=4 mg/L). VT-1161 and VT-1129 showed significant in vitro
      activity against the majority of the 31 mucosal clinical isolates (MIC50 0.03 and
      0.06 mg/L, respectively), including Candida glabrata (MIC50, 0.125 and 0.25 mg/L,
      respectively). After oral doses, VT-1161 and VT-1129 concentrations in mouse
      serum and tongues were well above their MIC50 values. VT-1161 was highly
      effective as treatment of both fluconazole-susceptible and -resistant
      oropharyngeal candidiasis in Act1-/- mice. Conclusions: VT-1129 and VT-1161
      exhibit significant in vitro activity against Candida strains, including
      fluconazole-resistant C. albicans and C. glabrata. VT-1161 administration in mice
      results in significant mucosal drug accumulation and eradicates infection caused
      by fluconazole-susceptible and -resistant Candida strains.

PMID- 29040638
TI  - Low serum progesterone on the day of embryo transfer is associated with a
      diminished ongoing pregnancy rate in oocyte donation cycles after artificial
      endometrial preparation: a prospective study.
AB  - STUDY QUESTION: Is there a relationship between serum progesterone (P) and
      endometrial volume on the day of embryo transfer (ET) with ongoing pregnancy rate
      (OPR) in artificial endometrium preparation cycles? SUMMARY ANSWER: Patients with
      serum P < 9.2 ng/ml on the day of ET had a significantly lower OPR but
      endometrial volume was not related with OPR. WHAT IS KNOWN ALREADY: A window of
      optimal serum P levels during the embryo implantation period has been described
      in artificial endometrium preparation cycles. A very low endometrial volume is
      related to poor reproductive outcome. STUDY DESIGN, SIZE, DURATION: Prospective
      cohort study with 244 patients who underwent ET in an oocyte donation cycle after
      an artificial endometrial preparation cycle with estradiol valerate and vaginal
      micronized progesterone (400 mg/12 h). The study period went from 22 February
      2016 to 25 October 2016 (8 months). Sample size was calculated to detect a 20%
      difference in OPR (35-55%) between two groups according to serum P levels in a
      two-sided test (80% statistical power, 95% confidence interval (CI)).
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients undergoing their first/second
      oocyte donation cycle, aged <50, BMI < 30 kg/m2, triple layer endometrium >6.5 mm
      and 1-2 good quality transferred blastocysts. A private infertility centre. Serum
      P determination and 3D ultrasound of uterine cavity were performed on the day of
      ET. Endometrial volume measurements were taken using a virtual organ computer
      aided analysis (VOCALTM) system. The primary endpoint was OPR beyond pregnancy
      week 12. MAIN RESULTS AND ROLE OF CHANCE: About 211 of the 244 recruited patients
      fulfilled all the inclusion/exclusion criteria. Mean serum P on the day of embryo
      transfer was 12.7 +/- 5.4 ng/ml (Centiles 25, 9.2; 50, 11.8; 75,15.8). OPRs
      according to serum P quartiles were: Q1: 32.7%; Q2: 49.1%; Q3: 58.5%; Q4: 50.9%.
      The OPR of Q1 was significantly lower than Q2-Q4: 32.7% versus 52.8%; P = 0.016;
      RR (95% CI): 0.62 (0.41-0.94). The mean endometrial volume was 3.4 +/- 1.9 ml.
      Serum P on the day of ET did not correlate with endometrial volume. A logistic
      regression analysis, adjusted for all the potential confounders, showed that OPR
      significantly lowered between women with serum P < 9.2 ng/ml versus >=9.2 ng/ml
      (OR: 0.297; 95%CI: 0.113-0.779); P = 0.013. The ROC curve showed a significant
      predictive value of serum P levels on the day of ET for OPR, with an AUC (95%CI)
      = 0.59 (0.51-0.67). LIMITATIONS, REASONS FOR CAUTION: Only the women with normal
      uterine cavity, appropriate endometrial thickness and good quality blastocysts
      transfer were included. Extrapolation to an unselected population or to other
      routes and/or doses of administering P needs to be validated. The role of
      endometrial volume could not be fully defined as very few patients presented a
      very low volume. WIDER IMPLICATIONS OF THE FINDINGS: The present study suggests a
      minimum threshold of serum P values on the day of ET that needs to be reached in
      artificial endometrial preparation cycles to optimize outcome. No upper threshold
      could be defined. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION
      NUMBER: NCT02696694.

PMID- 29040639
TI  - The medical science DMZ: a network design pattern for data-intensive medical
      science.
AB  - Objective: We describe a detailed solution for maintaining high-capacity, data
      intensive network flows (eg, 10, 40, 100 Gbps+) in a scientific, medical context
      while still adhering to security and privacy laws and regulations. Materials and
      Methods: High-end networking, packet-filter firewalls, network intrusion
      detection systems. Results: We describe a "Medical Science DMZ" concept as an
      option for secure, high-volume transport of large, sensitive datasets between
      research institutions over national research networks, and give 3 detailed
      descriptions of implemented Medical Science DMZs. Discussion: The exponentially
      increasing amounts of "omics" data, high-quality imaging, and other rapidly
      growing clinical datasets have resulted in the rise of biomedical research "Big
      Data." The storage, analysis, and network resources required to process these
      data and integrate them into patient diagnoses and treatments have grown to
      scales that strain the capabilities of academic health centers. Some data are not
      generated locally and cannot be sustained locally, and shared data repositories
      such as those provided by the National Library of Medicine, the National Cancer
      Institute, and international partners such as the European Bioinformatics
      Institute are rapidly growing. The ability to store and compute using these data
      must therefore be addressed by a combination of local, national, and industry
      resources that exchange large datasets. Maintaining data-intensive flows that
      comply with the Health Insurance Portability and Accountability Act (HIPAA) and
      other regulations presents a new challenge for biomedical research. We describe a
      strategy that marries performance and security by borrowing from and redefining
      the concept of a Science DMZ, a framework that is used in physical sciences and
      engineering research to manage high-capacity data flows. Conclusion: By
      implementing a Medical Science DMZ architecture, biomedical researchers can
      leverage the scale provided by high-performance computer and cloud storage
      facilities and national high-speed research networks while preserving privacy and
      meeting regulatory requirements.

PMID- 29040641
TI  - Emerging models on the regulation of intercellular transport by plasmodesmata
      associated callose.
AB  - The intercellular transport of molecules through membranous channels that
      traverse the cell walls-so-called plasmodesmata-is of fundamental importance for
      plant development. Regulation of plasmodesmata aperture (and transport capacity)
      is mediated by changes in the flanking cell walls, mainly via the
      synthesis/degradation (turnover) of the (1,3)-beta-glucan polymer callose. The
      role of callose in organ development and in plant environmental responses is well
      recognized, but detailed understanding of the mechanisms regulating its
      accumulation and its effects on the structure and permeability of the channels is
      still missing. We compiled information on the molecular components and signalling
      pathways involved in callose turnover at plasmodesmata and, more generally, on
      the structural and mechanical properties of (1,3)-beta-glucan polymers in cell
      walls. Based on this revision, we propose models integrating callose, cell walls,
      and the regulation of plasmodesmata structure and intercellular communication. We
      also highlight new tools and interdisciplinary approaches that can be applied to
      gain further insight into the effects of modifying callose in cell walls and its
      consequences for intercellular signalling.

PMID- 29040640
TI  - Pathology-MRI Correlations in Diffuse Low-Grade Epilepsy Associated Tumors.
AB  - It is recognized that IDH mutation negative, low-grade epilepsy associated tumors
      (LEAT) can show diffuse growth patterns and lack the diagnostic hallmarks of
      either classical dysembryoplastic neuroepithelial tumors (DNT) or typical
      ganglioglioma. "Nonspecific or diffuse DNT" and more recently "polymorphous low
      grade neuroepithelial tumor of the young" have been terms used for these
      entities. There are few reports on the MRI recognition of these diffuse
      glioneuronal tumors (dGNT), which is important in planning the extent of surgical
      resection. In 27 LEATs T1, T2, FLAIR, and postcontrast T1 MRI were evaluated and
      the pathology reviewed, including immunostaining for NeuN, CD34, MAP2, and IDH1.
      Each case was then independently classified by pathology or MRI as simple DNT,
      complex DNT, or dGNT. There was agreement in 23/27 (85%; Kappa score 0.62; p <
      0.01). In 4 cases, there was discrepancy in the diagnosis of simple versus
      complex DNT but 100% agreement achieved for dGNT. DNT showed significantly more
      expansion of the cortex, cystic change and ventricle extension than dGNT. dGNT
      showed significantly more subcortical T2w hyperintensity and focal cortical
      atrophy which correlated on pathology with CD34 expression, cortical neuronal
      loss and white matter rarefaction. There was no distinct cortical dysplasia
      component identified by MRI or pathology in any case. This study highlights that
      dGNT can be reliably discriminated on MRI from DNT.

PMID- 29040643
TI  - Description of Trichophoromyia velezbernali, a New Sand Fly Species (Diptera:
      Psychodidae: Phlebotominae) from Colombian Amazonia.
AB  - A new species of phlebotomine sand fly, Trichophoromyia velezbernali sp. n.
      Posada-Lopez, Galvis & Galati, from Colombian Amazonia is described with
      illustrations and images of male and female adults.

PMID- 29040642
TI  - Dynamic DNA binding, junction recognition and G4 melting activity underlie the
      telomeric and genome-wide roles of human CST.
AB  - Human CST (CTC1-STN1-TEN1) is a ssDNA-binding complex that helps resolve
      replication problems both at telomeres and genome-wide. CST resembles Replication
      Protein A (RPA) in that the two complexes harbor comparable arrays of OB-folds
      and have structurally similar small subunits. However, the overall architecture
      and functions of CST and RPA are distinct. Currently, the mechanism underlying
      CST action at diverse replication issues remains unclear. To clarify CST
      mechanism, we examined the capacity of CST to bind and resolve DNA structures
      found at sites of CST activity. We show that CST binds preferentially to ss-dsDNA
      junctions, an activity that can explain the incremental nature of telomeric C
      strand synthesis following telomerase action. We also show that CST unfolds G
      quadruplex structures, thus providing a mechanism for CST to facilitate
      replication through telomeres and other GC-rich regions. Finally, smFRET analysis
      indicates that CST binding to ssDNA is dynamic with CST complexes undergoing
      concentration-dependent self-displacement. These findings support an RPA-based
      model where dissociation and re-association of individual OB-folds allow CST to
      mediate loading and unloading of partner proteins to facilitate various aspects
      of telomere replication and genome-wide resolution of replication stress.

PMID- 29040644
TI  - Quality Improvement Feature Series Article 2: Displaying and Analyzing Quality
      Improvement Data.
AB  - In this second article in the quality improvement (QI) methods series, we discuss
      how data are best displayed and analyzed in QI projects while focusing on some
      similarities with and differences from traditional clinical research. We
      demonstrate why displaying data over time on a run or control chart is superior
      to using pre-post analysis for QI studies. We introduce several types of
      statistical process control charts for data commonly collected during QI programs
      and provide guidance on how to use the proper chart. Last, we present solutions
      to several common data challenges in QI projects.

PMID- 29040645
TI  - Erratum: Epidemiology and clinical characteristics of invasive mould infections:
      A multicenter, retrospective analysis in five Asian countries.

PMID- 29040646
TI  - Statins Affect Skeletal Muscle Performance: Evidence for Disturbances in Energy
      Metabolism.
AB  - Context: Statin myopathy is linked to disturbances in mitochondrial function and
      exercise intolerance. Objectives: To determine whether differences exist in
      exercise performance, muscle function, and muscle mitochondrial oxidative
      capacity and content between symptomatic and asymptomatic statin users, and
      control subjects. Design: Cross-sectional study. Setting: Department of
      Physiology, Radboud University Medical Center. Participants: Long-term
      symptomatic and asymptomatic statin users, and control subjects (n = 10 per
      group). Interventions: Maximal incremental cycling tests, involuntary
      electrically stimulated isometric quadriceps-muscle contractions, and biopsy of
      vastus lateralis muscle. Main Outcomes Measured: Maximal exercise capacity,
      substrate use during exercise, muscle function, and mitochondrial energy
      metabolism. Results: Peak oxygen uptake, maximal work load, and ventilatory
      efficiency were comparable between groups, but both statin groups had a depressed
      anaerobic threshold compared with the control group (P = 0.01). Muscle relaxation
      time was prolonged in both statin groups compared with the control group and rate
      of maximal force rise was decreased (Ptime*group < 0.001 for both measures).
      Mitochondrial activity of complexes II and IV was lower in symptomatic statin
      users than control subjects and tended to be lower for complex (C) III (CII: P =
      0.03; CIII: P = 0.05; CIV: P = 0.04). Mitochondrial content tended to be lower in
      both statin groups than in control subjects. Conclusion: Statin use attenuated
      substrate use during maximal exercise performance, induced muscle fatigue during
      repeated muscle contractions, and decreased muscle mitochondrial oxidative
      capacity. This suggests disturbances in mitochondrial oxidative capacity occur
      with statin use even in patients without statin-induced muscle complaints.

PMID- 29040647
TI  - Brain Capillary Ultrastructure in Idiopathic Normal Pressure Hydrocephalus:
      Relationship With Static and Pulsatile Intracranial Pressure.
AB  - Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease of
      unknown cause. We investigated the morphology of capillaries in frontal cortex
      biopsies from iNPH patients and related the observations to overnight
      intracranial pressure (ICP) scores. A biopsy (0.9*10 mm) was taken from where the
      ICP sensor subsequently was inserted. Brain capillaries were investigated by
      electron microscopy of biopsies from 27 iNPH patients and 10 reference subjects,
      i.e. patients (not healthy individuals) without cerebrospinal fluid circulation
      disturbances, in whom normal brain tissue was removed as part of necessary
      neurosurgical treatment. Degenerating and degenerated pericyte processes were
      identified in 23/27 (85%) iNPH and 6/10 (60%) of reference specimens. Extensive
      disintegration of pericyte processes were recognized in 11/27 (41%) iNPH and 1/10
      (10%) reference specimens. There were no differences in basement membrane (BM)
      thickness or pericyte coverage between iNPH and reference subjects. The pulsatile
      or static ICP scores did neither correlate with the BM thickness nor with
      pericyte coverage. We found increased prevalence of degenerating pericytes in
      iNPH while the BM thickness and pericyte coverage did not differ from the
      reference individuals. Observations in iNPH may to some extent be age-related
      since the iNPH patients were significantly older than the reference individuals.

PMID- 29040648
TI  - Molecular basis for asymmetry sensing of siRNAs by the Drosophila Loqs-PD/Dcr-2
      complex in RNA interference.
AB  - RNA interference defends against RNA viruses and retro-elements within an
      organism's genome. It is triggered by duplex siRNAs, of which one strand is
      selected to confer sequence-specificity to the RNA induced silencing complex
      (RISC). In Drosophila, Dicer-2 (Dcr-2) and the double-stranded RNA binding domain
      (dsRBD) protein R2D2 form the RISC loading complex (RLC) and select one strand of
      exogenous siRNAs according to the relative thermodynamic stability of base
      pairing at either end. Through genome editing we demonstrate that Loqs-PD, the
      Drosophila homolog of human TAR RNA binding protein (TRBP) and a paralog of R2D2,
      forms an alternative RLC with Dcr-2 that is required for strand choice of
      endogenous siRNAs in S2 cells. Two canonical dsRBDs in Loqs-PD bind to siRNAs
      with enhanced affinity compared to miRNA/miRNA* duplexes. Structural analysis,
      NMR and biophysical experiments indicate that the Loqs-PD dsRBDs can slide along
      the RNA duplex to the ends of the siRNA. A moderate but notable binding
      preference for the thermodynamically more stable siRNA end by Loqs-PD alone is
      greatly amplified in complex with Dcr-2 to initiate strand discrimination by
      asymmetry sensing in the RLC.

PMID- 29040649
TI  - ClusterCAD: a computational platform for type I modular polyketide synthase
      design.
AB  - ClusterCAD is a web-based toolkit designed to leverage the collinear structure
      and deterministic logic of type I modular polyketide synthases (PKSs) for
      synthetic biology applications. The unique organization of these megasynthases,
      combined with the diversity of their catalytic domain building blocks, has fueled
      an interest in harnessing the biosynthetic potential of PKSs for the microbial
      production of both novel natural product analogs and industrially relevant small
      molecules. However, a limited theoretical understanding of the determinants of
      PKS fold and function poses a substantial barrier to the design of active
      variants, and identifying strategies to reliably construct functional PKS
      chimeras remains an active area of research. In this work, we formalize a
      paradigm for the design of PKS chimeras and introduce ClusterCAD as a
      computational platform to streamline and simplify the process of designing
      experiments to test strategies for engineering PKS variants. ClusterCAD provides
      chemical structures with stereochemistry for the intermediates generated by each
      PKS module, as well as sequence- and structure-based search tools that allow
      users to identify modules based either on amino acid sequence or on the chemical
      structure of the cognate polyketide intermediate. ClusterCAD can be accessed at
      https://clustercad.jbei.org and at http://clustercad.igb.uci.edu.

PMID- 29040650
TI  - Interferon-Alpha Reduces Human Hippocampal Neurogenesis and Increases Apoptosis
      via Activation of Distinct STAT1-Dependent Mechanisms.
AB  - Background: In humans, interferon-alpha treatment for chronic viral hepatitis is
      a well-recognized clinical model for inflammation-induced depression, but the
      molecular mechanisms underlying these effects are not clear. Following peripheral
      administration in rodents, interferon-alpha induces signal transducer and
      activator of transcription-1 (STAT1) within the hippocampus and disrupts
      hippocampal neurogenesis. Methods: We used the human hippocampal progenitor cell
      line HPC0A07/03C to evaluate the effects of 2 concentrations of interferon-alpha,
      similar to those observed in human serum during its therapeutic use (500 pg/mL
      and 5000 pg/mL), on neurogenesis and apoptosis. Results: Both concentrations of
      interferon-alpha decreased hippocampal neurogenesis, with the high concentration
      also increasing apoptosis. Moreover, interferon-alpha increased the expression of
      interferon-stimulated gene 15 (ISG15), ubiquitin-specific peptidase 18 (USP18),
      and interleukin-6 (IL-6) via activation of STAT1. Like interferon-alpha, co
      treatment with a combination of ISG15, USP18, and IL-6 was able to reduce
      neurogenesis and enhance apoptosis via further downstream activation of STAT1.
      Further experiments showed that ISG15 and USP18 mediated the interferon-alpha
      induced reduction in neurogenesis (potentially through upregulation of the
      ISGylation-related proteins UBA7, UBE2L6, and HERC5), while IL-6 mediated the
      interferon-alpha-induced increase in apoptosis (potentially through
      downregulation of aquaporin 4). Using transcriptomic analyses, we showed that
      interferon-alpha regulated pathways involved in oxidative stress and immune
      response (e.g., Nuclear Factor (erythroid-derived 2)-like 2 [Nrf2] and interferon
      regulatory factor [IRF] signaling pathway), neuronal formation (e.g., CAMP
      response element-binding protein [CREB] signaling), and cell death regulation
      (e.g., tumor protein(p)53 signaling). Conclusions: We identify novel molecular
      mechanisms mediating the effects of interferon-alpha on the human hippocampus
      potentially involved in inflammation-induced neuropsychiatric symptoms.

PMID- 29040652
TI  - Two New Species and Seven New Records of Horse Fly (Diptera: Tabanidae) From
      Malaysia, Including a Description of New Species and Modified Keys.
AB  - Horse flies (Diptera: Tabanidae) are of medical and veterinary importance, as
      their blood-sucking feeding habit enables them to transmit several disease
      causing agents. In Malaysia, the family Tabanidae consists of 120 species
      belonging to eight genera. The current study describes two new species (Chrysops
      idlani sp. nov. and Tabanus ekor sp. nov.) and presents new records for seven
      species: Tabanus fontinalisSchuurmans Stekhoven, 1926; Tabanus
      fuscifronsSchuurmans Stekhoven, 1926, Tabanus latifasciesSchuurmans Stekhoven,
      1926, Tabanus megalops (Walker, 1854), Tabanus rhinargusPhilip, 1962, Tabanus
      salvazai (Surcouf, 1922), and Tabanus tristisWulp, 1881. Complete descriptions
      and illustrations are provided for the new species, and species variations for
      the new records are discussed. Male Tabanus latifasciesSchuurmans Stekhoven, 1926
      and Tabanus perakiensis Ricardo, 1911 are thoroughly described herein.

PMID- 29040651
TI  - The Chlamydomonas mex1 mutant shows impaired starch mobilization without maltose
      accumulation.
AB  - The MEX1 locus of Chlamydomonas reinhardtii was identified in a genetic screen as
      a factor that affects starch metabolism. Mutation of MEX1 causes a slow-down in
      the mobilization of storage polysaccharide. Cosegregation and functional
      complementation analyses were used to assess the involvement of the Mex1 protein
      in starch degradation. Heterologous expression experiments performed in
      Escherichia coli and Arabidopsis thaliana allowed us to test the capacity of the
      algal protein in maltose export. In contrast to the A. thaliana mex1 mutant, the
      mutation in C. reinhardtii does not lead to maltose accumulation and growth
      impairment. Although localized in the plastid envelope, the algal protein does
      not transport maltose efficiently across the envelope, but partly complements the
      higher plant mutant. Both Mex orthologs restore the growth of the E. coli ptsG
      mutant strain on glucose-containing medium, revealing the capacity of these
      proteins to transport this hexose. These findings suggest that Mex1 is essential
      for starch mobilization in both Chlamydomonas and Arabidopsis, and that this
      protein family may support several functions and not only be restricted to
      maltose export across the plastidial envelope.

PMID- 29040653
TI  - Regulatory mechanisms of sperm flagellar motility by metachronal and synchronous
      sliding of doublet microtubules.
AB  - STUDY QUESTION: What is the role of metachronal and synchronous sliding in sperm
      flagellar motility? SUMMARY ANSWER: Both metachronal and oscillatory synchronous
      sliding are essential for sperm flagellar motility, while the change in mode of
      synchronous sliding between the non-oscillatory synchronous sliding of a specific
      pair of the doublet microtubules and the oscillatory synchronous sliding between
      most pairs of doublet microtubules modulates the sperm flagellar motility. WHAT
      IS KNOWN ALREADY: Metachronal and synchronous sliding of doublet microtubules are
      involved in sperm flagellar motility and regulation of these sliding movements
      controls flagellar bend formation. STUDY DESIGN, SIZE, DURATION: To study the
      regulatory mechanisms of metachronal and synchronous sliding in flagellar
      movement of golden hamster spermatozoa, changes in these sliding movements during
      hyperactivation were examined by measuring the angle of the tangent to the
      flagellar shaft with reference to the central axis of the sperm head (the shear
      angle) along the flagellum. Golden hamster spermatozoa were obtained from the
      caudal epididymis of five sexually mature golden hamsters. Results from three
      experiments were averaged. The number of spermatozoa analyzed is 15 activated
      sperm, 22 hyperactivated sperm and 20 acrosome-reacted sperm.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: For detailed field-by-field analysis,
      an individual flagellar image was tracked automatically using the Autotrace
      module of image analysis software. The coordinate values of the flagellar shaft
      were used to calculate the shear angle, which is proportional to the amount of
      microtubule sliding at any given position along the flagellum. The maximum shear
      angles of metachronal and synchronous sliding were obtained from the mean shear
      angles between the maximum shear angles of pro-hook bends and the absolute values
      of the minimum shear angles of anti-hook bends, which represent the amplitude of
      a set of successive shear angle curves, with 3-12 shear curves covering one beat
      cycle of sperm flagellar movement. Asymmetry of flagellar waves was expressed by
      the mean shear angle between the maximum shear angle of pro-hook bends and the
      minimum shear angle of anti-hook bends at 100 MUm from the head-midpiece
      junction. MAIN RESULTS AND THE ROLE OF CHANCE: The asymmetrical flagellar
      movements observed in the activated (non-hyperactivated) and hyperactivated
      spermatozoa were characterized by the non-oscillatory synchronous sliding of a
      specific pair of the doublets; the large asymmetrical flagellar movement in the
      hyperactivated spermatozoa was generated by the large non-oscillatory synchronous
      sliding. Both the metachronal and synchronous sliding increased during the
      hyperactivation; however, the large symmetrical flagellar movement of the
      acrosome-reacted spermatozoa was characterized by the oscillatory synchronous
      sliding between most pairs of doublets. These results demonstrated that the
      metachronal and synchronous sliding are involved in generation and modulation of
      sperm flagellar motility; however, two types of synchronous sliding, non
      oscillatory and oscillatory sliding, modulate the sperm flagellar motility by
      enhancing the sliding of a specific pair of the doublets or the sliding between
      most pairs of the doublets. LARGE SCALE DATA: None. LIMITATIONS, REASONS FOR
      CAUTION: This is an indirect study of the metachronal and synchronous sliding of
      doublet microtubules. Studies based on the direct observation of behavior of
      dynein are needed to clarify the sliding microtubule theory of flagellar movement
      of spermatozoa. WIDER IMPLICATIONS OF THE FINDINGS: Both the metachronal and
      oscillatory synchronous sliding of doublet microtubule generate and modulate
      sperm flagellar motility, while the change in mode of synchronous sliding between
      the non-oscillatory synchronous sliding and oscillatory synchronous sliding
      modulates the sperm flagellar motility. The coordination between these sliding
      leads to various types of flagellar and ciliary motility, including the
      asymmetrical beating in flagellar and ciliary movement and planar or helical
      beating in sea urchin spermatozoa. Moreover, the finding that the metachronal
      sliding and two types of synchronous sliding generate and modulate the flagellar
      motility will open a new avenue for quantitative analysis of flagellar and
      ciliary motility. STUDY FUNDING AND COMPETING INTEREST(S): The authors have no
      conflict of interest and no funding to declare.

PMID- 29040654
TI  - Does Background Odor in Tea Gardens Mask Attractants? Screening and Application
      of Attractants for Empoasca onukii Matsuda.
AB  - Plant volatiles help herbivores to locate their hosts, and therefore, they could
      be used to help develop pesticide-free pest management strategies. To develop an
      attractant for tea leafhopper (Empoasca onukii), we screened nine tea plant
      volatile compounds for their attractiveness using Y-tube olfactometer assays.
      Results indicated that tea leafhoppers significantly preferred ocimene, limonene,
      (Z)-3-hexenol, and (Z)-3-hexenyl acetate over clean air. These compounds were
      combined in a blend which lost its attractiveness at concentrations below 10-2
      g/ml in liquid paraffin. In field tests, the blend was attractive to leafhoppers
      only in autumn, but not in summer. Analyses of the tea field background odor
      showed that all four components of the blend were present at much higher
      concentrations in summer (0.05-0.001 ng/liter) than in autumn (~10- to 25-fold
      lower). In field Y-tube bioassays, compared with the tea field background odor,
      the blend was attractive at a concentration of 10-1 g/ml in liquid paraffin, but
      not at 10-2 g/ml. These results suggest that field background odor can disrupt
      the attractiveness of an attractant based on plant volatiles to herbivores.

PMID- 29040655
TI  - Effects of 1950 MHz radiofrequency electromagnetic fields on Abeta processing in
      human neuroblastoma and mouse hippocampal neuronal cells.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease leading to progressive
      loss of memory and other cognitive functions. One of the well-known pathological
      markers of AD is the accumulation of amyloid-beta protein (Abeta), and its
      plaques, in the brain. Recent studies using Tg-5XFAD mice as a model of AD have
      reported that exposure to radiofrequency electromagnetic fields (RF-EMF) from
      cellular phones reduced Abeta plaques in the brain and showed beneficial effects
      on AD. In this study, we examined whether exposure to 1950 MHz RF-EMF affects
      Abeta processing in neural cells. We exposed HT22 mouse hippocampal neuronal
      cells and SH-SY5Y human neuroblastoma cells to RF-EMF (SAR 6 W/kg) for 2 h per
      day for 3 days, and analyzed the mRNA and protein expression of the key genes
      related to Abeta processing. When exposed to RF-EMF, mRNA levels of APP, BACE1,
      ADAM10 and PSEN1 were decreased in HT22, but the mRNA level of APP was not
      changed in SH-SY5Y cells. The protein expression of APP and BACE1, as well as the
      secreted Abeta peptide, was not significantly different between RF-EMF-exposed 7w
      PSML, HT22 and SH-SY5Y cells and the unexposed controls. These observations
      suggest that RF-EMF exposure may not have a significant physiological effect on
      Abeta processing of neural cells in the short term. However, considering that we
      only exposed HT22 and SH-SY5Y cells to RF-EMF for 2 h per day for 3 days, we
      cannot exclude the possibility that 1950 MHz RF-EMF induces physiological change
      in Abeta processing with long-term and continuous exposure.

PMID- 29040656
TI  - Barriers to the success of an electronic pharmacovigilance reporting system in
      Kenya: an evaluation three years post implementation.
AB  - Objective: Electronic pharmacovigilance reporting systems are being implemented
      in many developing countries in an effort to improve reporting rates. This study
      sought to establish the factors that acted as barriers to the success of an
      electronic pharmacovigilance reporting system in Kenya 3 years after its
      implementation. Materials and Methods: Factors that could act as barriers to
      using electronic reporting systems were identified in a review of literature and
      then used to develop a survey questionnaire that was administered to pharmacists
      working in government hospitals in 6 counties in Kenya. Results: The survey was
      completed by 103 out of the 115 targeted pharmacists (89.5%) and included free
      text comments. The key factors identified as barriers were: unavailable,
      unreliable, or expensive Internet access; challenges associated with a hybrid
      system of paper and electronic reporting tools; and system usability issues.
      Coordination challenges at the national pharmacovigilance center and changes in
      the structure of health management in the country also had an impact on the
      success of the electronic reporting system. Discussion: Different personal,
      organizational, infrastructural, and reporting system factors affect the success
      of electronic reporting systems in different ways, depending on the context.
      Context-specific formative evaluations are useful in establishing the performance
      of electronic reporting systems to identify problems and ensure that they achieve
      the desired objectives. Conclusion: While several factors hindered the optimal
      use of the electronic pharmacovigilance reporting system in Kenya, all were
      considered modifiable. Effort should be directed toward tackling the identified
      issues in order to facilitate use and improve pharmacovigilance reporting rates.

PMID- 29040658
TI  - Fire Does Not Strongly Affect Genetic Diversity or Structure of a Common Treefrog
      in the Endangered Florida Scrub.
AB  - Fire regimes influence natural populations of organisms in diverse ways, via
      direct effects on population dynamics as well as indirect effects on habitat and
      ecosystem processes. Although many amphibian species have evolved to persist in
      fire-dependent ecosystems, the effects of fire on the genetic diversity of
      amphibian populations remain relatively unexplored. We examined how different
      aspects of fire history relate to population genetic diversity and structure of
      an abundant anuran, Hyla femoralis, in a large, intact area of Florida scrub
      containing hundreds of seasonally inundated ponds. Specifically, we assessed the
      overall population genetic structure and examined whether variation in time since
      fire, fire intensity, or historical fire frequency at breeding sites explained
      spatial variation in genetic diversity. Based on our sampling of 17 breeding
      aggregations within the 2,100-ha study area, neither recent nor frequent fire
      reduce genetic diversity or restrict connectivity among ponds for H. femoralis.
      Overall, mean effective population sizes were large (average range = 68-572). We
      detected a positive trend between effective population size (Ne) and average
      intensity of the most-recent fire, with this factor explaining 42% of the
      variation in Ne. Our results contrast with previous studies that consistently
      demonstrate strong relationships between fire history and population genetic
      structure of scrub-associated lizard species, suggesting that H. femoralis is
      resilient to a wide range of fire regimes. More generally, our study contributes
      to understanding the roles of life-history characteristics and environmental
      unpredictability in shaping organisms' responses to fire.

PMID- 29040657
TI  - Highly Expressed Genes Are Preferentially Co-Opted for C4 Photosynthesis.
AB  - Novel adaptations are generally assembled by co-opting pre-existing genetic
      components, but the factors dictating the suitability of genes for new functions
      remain poorly known. In this work, we used comparative transcriptomics to
      determine the attributes that increased the likelihood of some genes being co
      opted for C4 photosynthesis, a convergent complex trait that boosts productivity
      in tropical conditions. We show that independent lineages of grasses repeatedly
      co-opted the gene lineages that were the most highly expressed in non-C4
      ancestors to produce their C4 pathway. Although ancestral abundance in leaves
      explains which genes were used for the emergence of a C4 pathway, the tissue
      specificity has surprisingly no effect. Our results suggest that levels of key
      genes were elevated during the early diversification of grasses and subsequently
      repeatedly used to trigger a weak C4 cycle via relatively few mutations. The
      abundance of C4-suitable transcripts therefore facilitated physiological
      innovation, but the transition to a strong C4 pathway still involved consequent
      changes in expression levels, leaf specificity, and coding sequences. The
      direction and amount of changes required for the strong C4 pathway depended on
      the identity of the genes co-opted, so that ancestral gene expression both
      facilitates adaptive transitions and constrains subsequent evolutionary
      trajectories.

PMID- 29040659
TI  - The epidemiological challenge of traditional chronic disease risk factors in
      emerging economies.

PMID- 29040660
TI  - Potential of Three Trap Crops in Managing Nezara viridula (Hemiptera:
      Pentatomidae) on Tomatoes in Florida.
AB  - The southern green stink bug, Nezara viridula (L.) (Hemiptera: Pentatomidae), is
      a serious insect pest of tomatoes in Florida. In this study, we examined the use
      of three species of trap crops to manage N. viridula in North Florida tomato
      crops in 2014 and 2015. We used striped sunflower (Helianthus annuus) (Asterales:
      Asteraceae) and wild game feed sorghum (Sorghum bicolor) (Poales: Poaceae) in
      both years, but different species of millet each year: browntop millet (Panicum
      ramosum) (Poales: Poaceae) in 2014 and pearl millet (Pennisetum glaucum) (Poales:
      Poaceae) in 2015. The number of stink bug adults collected from wild game feed
      sorghum exceeded the number from sunflower, and none were collected from either
      species of millet. Sorghum attracted a significantly higher number of adults than
      did striped sunflower; however, both sunflower and sorghum attracted the adults
      of N. viridula. Adults of the pest feed on the sorghum panicle and sunflower head
      (inflorescence). Although fewer stink bugs were found feeding on sunflower, the
      sunflower was found to be a good source of other natural enemies and pollinators
      and also attracted significantly greater numbers of the brown stink bug
      Euschistus servus (Say) (Hemiptera: Pentatomidae) (another pest of tomatoes).
      While this study demonstrated the effectiveness of sorghum, we recommend that
      sorghum be planted with another trap crop, preferably sunflower, for better
      preventive control of the southern green stink bug.

PMID- 29040661
TI  - Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infections
      in Pediatric Hematopoietic Stem Cell Transplant Recipients.

PMID- 29040662
TI  - Molecular subtyping of tumors from patients with familial glioma.
AB  - Background: Single-gene mutation syndromes account for some familial glioma (FG);
      however, they make up only a small fraction of glioma families. Gliomas can be
      classified into 3 major molecular subtypes based on isocitrate dehydrogenase
      (IDH) mutation and 1p/19q codeletion. We hypothesized that the prevalence of
      molecular subtypes might differ in familial versus sporadic gliomas and that
      tumors in the same family should have the same molecular subtype. Methods:
      Participants in the FG study (Gliogene) provided samples for germline DNA
      analysis. Formalin-fixed, paraffin-embedded tumors were obtained from a subset of
      FG cases, and DNA was extracted. We analyzed tissue from 75 families, including
      10 families containing a second affected family member. Copy number variation
      data were obtained using a first-generation Affymetrix molecular inversion probe
      (MIP) array. Results: Samples from 62 of 75 (83%) FG cases could be classified
      into the 3 subtypes. The prevalence of the molecular subtypes was: 30 (48%) IDH
      wildtype, 21 (34%) IDH-mutant non-codeleted, and 11 (19%) IDH-mutant and 1p/19q
      codeleted. This distribution of molecular subtypes was not statistically
      different from that of sporadic gliomas (P = 0.54). Of 10 paired FG samples,
      molecular subtypes were concordant for 7 (kappa = 0.59): 3 IDH-mutant non
      codeleted, 2 IDH-wildtype, and 2 IDH-mutant and 1p/19q codeleted gliomas.
      Conclusions: Our data suggest that within individual families, patients develop
      gliomas of the same molecular subtype. However, we did not observe differences in
      the prevalence of the molecular subtypes in FG compared with sporadic gliomas.
      These observations provide further insight into the distribution of molecular
      subtypes in FG.

PMID- 29040663
TI  - Heart-type fatty acid-binding protein (H-FABP) and highly sensitive troponin T
      (hsTnT) as markers of myocardial injury and cardiovascular events in elective
      percutaneous coronary intervention (PCI).
AB  - Background/Introduction: Type 4a myocardial infarction (MI) occurs when
      myocardial injury is combined with either symptoms suggestive of myocardial
      ischaemia, new left bundle branch block, angiographic loss of patency of a major
      artery or imaging suggestive of new loss of myocardium. Myocardial injury is
      defined as a rise of >5 x 99th upper reference limit (URL) of 14 ng/l (i.e. >70
      ng/l) for highly sensitive troponin T (hsTnT) at 6 h if hsTnT was normal at
      baseline or >20% rise from 0 to 6 h if hsTnT was >14 ng/l at baseline. Aim: To
      assess the prognostic value of biomarkers of myocardial injury following elective
      percutaneous coronary intervention (PCI). Design: A cohort of 209 patients were
      included of whom 144 (68.9%) were male, mean age was 68.8 years, 28 (13.4%) were
      smokers, 31 (14.8%) were diabetic, 199 (95.2%) had hypercholesterolaemia and 138
      (66.0%) had hypertension. Methods: We evaluated hsTnT, heart-type fatty acid
      binding protein (H-FABP), troponin I (TnI), creatine kinase MB type (CKMB),
      myoglobin, glycogen phosphorylase BB (GPBB) and carbonic anhydrase III (CA III)
      at 0, 4, 6 and 24 h following elective PCI. Patients were followed up at 1 year
      to assess for major adverse clinical events (MACE). Results: Myocardial injury
      was observed in 37 (17.7%) patients. Median hsTnT/H-FABP at 4 h were most
      predictive. MACE was noted in 6 (2.9%) patients, 3 had type 4a MI post PCI, P =
      0.036. Discussion/Conclusions: Median 4 h hsTnT/H-FABP were most predictive of
      myocardial injury following PCI. H-FABP and hsTnT were predictive of MACE.

PMID- 29040664
TI  - Coumestrol induces mitochondrial dysfunction by stimulating ROS production and
      calcium ion influx into mitochondria in human placental choriocarcinoma cells.
AB  - STUDY QUESTION: Does coumestrol inhibit proliferation of human placental
      choriocarcinoma cells? SUMMARY ANSWER: Coumestrol promotes cell death in the
      choriocarcinoma cells by regulating ERK1/2 MAPK and JNK MAPK signaling pathways
      and through disruption of Ca2+ and ROS homeostasis. WHAT IS KNOWN ALREADY: A
      number of patients who suffer from choriocarcinomas fail to survive due to
      delayed diagnosis or a recurrent tumor and resistance to traditional chemotherapy
      using platinum-based agents and methotrexate. To overcome these limitations, it
      is important to discover novel compounds which have no adverse effects yet can
      inhibit the expression of a target molecule to develop, as a novel therapeutic
      for prevention and/or treatment of choriocarcinomas. STUDY DESIGN, SIZE,
      DURATION: Effects of coumestrol on human placental choriocarcinoma cell lines,
      JAR and JEG3, were assessed in diverse assays in a dose- and time-dependent
      manner. PARTICIPCANTS/MATERIALS, SETTING, METHODS: Effects of coumestrol on cell
      proliferation, apoptosis (annexin V expression, propidium iodide staining, TUNEL
      and invasion assays), mitochondria-mediated apoptosis, production of reactive
      oxygen species (ROS), lipid peroxidation, glutathione levels and endoplasmic
      reticulum (ER) stress proteins in JAR and JEG3 cells were determined. Signal
      transduction pathways in JAR and JEG3 cells in response to coumestrol were
      determined by western blot analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Results
      of the present study indicated that coumestrol suppressed proliferation and
      increased apoptosis in JAR and JEG3 cells by inducing pro-apoptotic proteins, Bax
      and Bak. In addition, coumestrol increased ROS production, as well as lipid
      peroxidation and glutathione levels in JAR and JEG3 cells. Moreover, coumestrol
      induced depolarization of mitochondrial membrane potential (MMP) and increased
      cytosolic and mitochondrial Ca2+ levels in JAR and JEG3 cells. Consistent with
      those results, treatment of JAR and JEG3 cells with a Ca2+ chelator and an
      inhibitor of IP3 receptor decreased coumestrol-induced depolarization of MMP and
      increased proliferation in JAR and JEG3 cells. LARGE SCALE DATA: N/A.
      LIMITATIONS, REASONS FOR CAUTION: A lack of in vivo animal studies is a major
      limitation of this research. The effectiveness of coumestrol to induce apoptosis
      of human placental choriocarcinoma cells requires further investigation. WIDER
      IMPLICATIONS OF THE FINDINGS: Our results indicate that coumestrol induces
      apoptotic effects on placental choriocarcinoma cells by regulating cell signaling
      and mitochondrial-mediated functions, with a potential to impair progression of
      the cancer. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by
      grants from the Korea Health Technology R&D Project through the Korea Health
      Industry Development Institute (KHIDI), funded by the Ministry of Health &
      Welfare, Republic of Korea (No. HI15C0810 awarded to G.S. and HI17C0929 awarded
      to W.L.).

PMID- 29040665
TI  - Systematic classification of the His-Me finger superfamily.
AB  - The His-Me finger endonucleases, also known as HNH or betabetaalpha-metal
      endonucleases, form a large and diverse protein superfamily. The His-Me finger
      domain can be found in proteins that play an essential role in cells, including
      genome maintenance, intron homing, host defense and target offense. Its overall
      structural compactness and non-specificity make it a perfectly-tailored
      pathogenic module that participates on both sides of inter- and intra-organismal
      competition. An extremely low sequence similarity across the superfamily makes it
      difficult to identify and classify new His-Me fingers. Using state-of-the-art
      distant homology detection methods, we provide an updated and systematic
      classification of His-Me finger proteins. In this work, we identified over 100
      000 proteins and clustered them into 38 groups, of which three groups are new and
      cannot be found in any existing public domain database of protein families. Based
      on an analysis of sequences, structures, domain architectures, and genomic
      contexts, we provide a careful functional annotation of the poorly characterized
      members of this superfamily. Our results may inspire further experimental
      investigations that should address the predicted activity and clarify the
      potential substrates, to provide more detailed insights into the fundamental
      biological roles of these proteins.

PMID- 29040666
TI  - Maternal Tenofovir Disoproxil Fumarate Use During Pregnancy Is Not Associated
      With Adverse Perinatal Outcomes Among HIV-infected East African Women: A
      Prospective Study.
AB  - Background: Tenofovir disoproxil fumarate (TDF) is commonly used in
      antiretroviral treatment (ART) and pre-exposure prophylaxis regimens. We
      evaluated the relationship between adverse perinatal outcomes and prenatal TDF
      use. Methods: Longitudinal data were analyzed from human immunodeficiency virus
      (HIV)-infected women who became pregnant during 2 HIV prevention studies
      conducted among HIV-serodiscordant couples in Kenya and Uganda. Pregnancies
      included were singleton, not terminated by an induced abortion, and had
      documented 3-drug ART use. Multivariate generalized estimating equation models
      were used to determine the association of prenatal TDF and perinatal outcomes.
      Results: The most frequent ART regimens were TDF/3TC/EFV (39%) and AZT/3TC/NVP
      (34%); 49% of pregnancies had prenatal TDF exposure and 6% used a protease
      inhibitor. Neonatal death, preterm birth, and pregnancy loss occurred in 2%, 8%,
      and 12% of pregnancies, respectively. No differences were observed between
      pregnancies with and without exposure to TDF in the frequency of pregnancy loss
      (adjusted prevalence rate ratio [aPRR] 1.19, P = .8) or neonatal death (aPRR
      0.68, P = .6). Preterm birth occurred less frequently among pregnancies exposed
      to TDF (aPRR, 0.34, P = .02). Conclusion: Maternal TDF use did not adversely
      affect perinatal outcomes.

PMID- 29040667
TI  - Data Resource Profile: The Nordic Obesity Surgery Cohort (NordOSCo).

PMID- 29040669
TI  - Basic domain of telomere guardian TRF2 reduces D-loop unwinding whereas Rap1
      restores it.

PMID- 29040668
TI  - Aurora Kinase B, a novel regulator of TERF1 binding and telomeric integrity.
AB  - AURKB (Aurora Kinase B) is a serine/threonine kinase better known for its role at
      the mitotic kinetochore during chromosome segregation. Here, we demonstrate that
      AURKB localizes to the telomeres in mouse embryonic stem cells, where it
      interacts with the essential telomere protein TERF1. Loss of AURKB function
      affects TERF1 telomere binding and results in aberrant telomere structure. In
      vitro kinase experiments successfully identified Serine 404 on TERF1 as a
      putative AURKB target site. Importantly, in vivo overexpression of S404-TERF1
      mutants results in fragile telomere formation. These findings demonstrate that
      AURKB is an important regulator of telomere structural integrity.

PMID- 29040670
TI  - Virus taxonomy: the database of the International Committee on Taxonomy of
      Viruses (ICTV).
AB  - The International Committee on Taxonomy of Viruses (ICTV) is charged with the
      task of developing, refining, and maintaining a universal virus taxonomy. This
      task encompasses the classification of virus species and higher-level taxa
      according to the genetic and biological properties of their members; naming virus
      taxa; maintaining a database detailing the currently approved taxonomy; and
      providing the database, supporting proposals, and other virus-related information
      from an open-access, public web site. The ICTV web site (http://ictv.global)
      provides access to the current taxonomy database in online and downloadable
      formats, and maintains a complete history of virus taxa back to the first release
      in 1971. The ICTV has also published the ICTV Report on Virus Taxonomy starting
      in 1971. This Report provides a comprehensive description of all virus taxa
      covering virus structure, genome structure, biology and phylogenetics. The ninth
      ICTV report, published in 2012, is available as an open-access online publication
      from the ICTV web site. The current, 10th report (http://ictv.global/report/), is
      being published online, and is replacing the previous hard-copy edition with a
      completely open access, continuously updated publication. No other database or
      resource exists that provides such a comprehensive, fully annotated compendium of
      information on virus taxa and taxonomy.

PMID- 29040671
TI  - Nanoscale dynamics of centromere nucleosomes and the critical roles of CENP-A.
AB  - In the absence of a functioning centromere, chromosome segregation becomes
      aberrant, leading to an increased rate of aneuploidy. The highly specific
      recognition of centromeres by kinetochores suggests that specific structural
      characteristics define this region, however, the structural details and mechanism
      underlying this recognition remains a matter of intense investigation. To address
      this, high-speed atomic force microscopy was used for direct visualization of the
      spontaneous dynamics of CENP-A nucleosomes at the sub-second time scale. We
      report that CENP-A nucleosomes change conformation spontaneously and reversibly,
      utilizing two major pathways: unwrapping, and looping of the DNA; enabling core
      transfer between neighboring DNA substrates. Along with these nucleosome dynamics
      we observed that CENP-A stabilizes the histone core against dissociating to
      histone subunits upon unwrapping DNA, unique from H3 cores which are only capable
      of such plasticity in the presence of remodeling factors. These findings have
      implications for the dynamics and integrity of nucleosomes at the centromere.

PMID- 29040672
TI  - Unsupervised Learning of Spatiotemporal Interictal Discharges in Focal Epilepsy.
AB  - BACKGROUND: Interictal epileptiform discharges are an important biomarker for
      localization of focal epilepsy, especially in patients who undergo chronic
      intracranial monitoring. Manual detection of these pathophysiological events is
      cumbersome, but is still superior to current rule-based approaches in most
      automated algorithms. OBJECTIVE: To develop an unsupervised machine-learning
      algorithm for the improved, automated detection and localization of interictal
      epileptiform discharges based on spatiotemporal pattern recognition. METHODS: We
      decomposed 24 h of intracranial electroencephalography signals into basis
      functions and activation vectors using non-negative matrix factorization (NNMF).
      Thresholding the activation vector and the basis function of interest detected
      interictal epileptiform discharges in time and space (specific electrodes),
      respectively. We used convolutive NNMF, a refined algorithm, to add a temporal
      dimension to basis functions. RESULTS: The receiver operating characteristics for
      NNMF-based detection are close to the gold standard of human visual-based
      detection and superior to currently available alternative automated approaches
      (93% sensitivity and 97% specificity). The algorithm successfully identified
      thousands of interictal epileptiform discharges across a full day of
      neurophysiological recording and accurately summarized their localization into a
      single map. Adding a temporal window allowed for visualization of the archetypal
      propagation network of these epileptiform discharges. CONCLUSION: Unsupervised
      learning offers a powerful approach towards automated identification of recurrent
      pathological neurophysiological signals, which may have important implications
      for precise, quantitative, and individualized evaluation of focal epilepsy.

PMID- 29040673
TI  - Assimilation of 'omics' strategies to study the cuticle layer and suberin
      lamellae in plants.
AB  - The assembly of the lipophilic cuticle layer and suberin lamellae, approximately
      450 million years ago, was a major evolutionary development that enabled plants
      to colonize terrestrial habitats. The cuticle layer is composed of cutin
      polyester and embedded cuticular waxes, whereas the suberin lamellae consist of
      very long chain fatty acid derivatives, glycerol, and phenolics cross-linked with
      alkyl ferulate-embedded waxes. Due to their substantial biological roles in plant
      life, the mechanisms underlying the assembly of these structures have been
      extensively investigated. In the last decade, the introduction of 'omics'
      approaches, including genomics, transcriptomics, proteomics, and metabolomics,
      have been key in the identification of novel genetic and chemical elements
      involved in the formation and function of the cuticle layer and suberin lamellae.
      This review summarizes contemporary studies that utilized various large-scale,
      'omics' strategies in combination with novel technologies to unravel how building
      blocks and polymers of these lipophilic barriers are made, and moreover linking
      structure to function along developmental programs and stress responses. We
      anticipate that the studies discussed here will inspire scientists studying
      lipophilic barriers to integrate complementary 'omics' approaches in their
      efforts to tackle as yet unresolved questions and engage the main challenges of
      the field to date.

PMID- 29040674
TI  - Evaluation of apoptotic- and autophagic-related protein expressions before and
      after IVM of fresh, slow-frozen and vitrified pre-pubertal mouse testicular
      tissue.
AB  - STUDY QUESTION: Do freezing and in vitro culture procedures enhance the
      expression of proteins involved in apoptotic or autophagic pathways in murine pre
      pubertal testicular tissue? SUMMARY ANSWER: IVM strongly modified apoptosis- and
      autophagy-related relative protein levels in mice testicular tissue whereas the
      impact of cryopreservation procedures was minimal at the end of the culture. WHAT
      IS KNOWN ALREADY: In vitro spermatogenesis remains a challenging technical issue
      as it imposes to find a very close balance between survival and death of germ
      cell natural precursors (i.e. gonocytes and spermatogonia), which will eventually
      undergo a complete spermatogenesis close to in vivo conditions. The establishment
      of efficient culture conditions coupled with suitable cryopreservation procedures
      (e.g. controlled slow freezing [CSF] and solid surface vitrification [SSV]) of
      pre-pubertal testicular tissue is a crucial step in the fields of fertility
      preservation and restoration to improve the spermatic yield obtained in vitro.
      STUDY DESIGN, SIZE, DURATION: Here, we study cryopreservation procedures (i.e.
      CSF or SSV) and the impact of culture media compositions. A first set of 66 mouse
      pre-pubertal testes were directly cultured during 30, 36, 38 and 60 days (D) from
      2.5 to 6.5-day-old CD-1 mice to evaluate the impact of time-aspect of culture and
      to endorse the reverse phase protein microarrays (RPPM) technique as an adapted
      experimental tool for the field of in vitro spermatogenesis. Ninety others fresh,
      slow-frozen and vitrified pre-pubertal testes were cultured during 30 days for
      the principal study to evaluate the impact of cryopreservation procedures before
      and after culture. Thirty-four testes dissected from 2.5, 6.5, 36.5, 40.5, 42.5
      and 62.5 days postpartum (dpp) mice, corresponding to the time frames of
      spermatogenesis orchestrated in vitro, were used as in vivo controls.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: After in vitro culture, testicular
      tissue samples originated from 2.5 or 6.5-day-old CD-1 male mice were analyzed
      using RPPM. This targeted proteomic technique allowed us to assess the expression
      level of 29 apoptosis- and autophagy-related factors by normalizing blank
      corrected signal values. In addition, morphological analyses (e.g. HES, PAS,
      TRA98 and CREM) and DNA fragmentation in intra-tubular cells (i.e. terminal
      deoxynucleotidyl transferase dUTP nick end labeling; TUNEL) were assessed for the
      distinct experimental conditions tested as well as for in vivo control mouse
      testes. MAIN RESULTS AND THE ROLE OF CHANCE: A validation of the RPPM procedure
      in the field of in vitro spermatogenesis was completed with assay and array
      robustness before a principal study concerning the evaluation of the impact of in
      vitro culture and cryopreservation procedures. The proportion of elongated
      spermatids and the total cell number per seminiferous tubule tended to be very
      different between the in vivo and in vitro conditions (P < 0.05), suggesting the
      presence of a beneficial regulation on the first spermatogenesis wave by
      intrinsic apoptosis (Caspase_9) and autophagy (Atg5) factors (P < 0.0003 and r2 =
      0.74). Concerning the impact of culture media compositions, a basic medium (BM)
      composed of alphaMEM plus 10% KnockOutTM serum replacement and gentamicin
      supplemented with retinol (Rol) and vitamin E (Vit. E) was selected as the best
      culture medium for fresh 6.5 dpp tissue cultured during 30D with 27.7 +/- 8.10%
      of seminiferous tubules containing elongated spermatids. Concerning the impact of
      cryopreservation procedures, SSV did not have any impact on the morphological
      parameters evaluated after culture in comparison to fresh tissue (FT) controls.
      The proportion of tubules with elongated spermatids on testicular explants
      cultured with BMRol+Vit. E was not different between SSV (6.6 +/- 1.6%) and CSF
      (5.3 +/- 1.9%); however, round spermatids were observed more frequently for SSV
      (19 +/- 6.2%) than CSF (3.3 +/- 1.9%, P = 0.0317). Even if the proportion of
      TUNEL-positive cells for BMRol+Vit. E was higher at D30 after SSV (4.12 +/-
      0.26%) than CSF (1.86 +/- 0.12%, P = 0.0022) and FT (2.69 +/- 0.33%, P = 0.0108),
      the DNA damages observed at the end of the culture (i.e. D30) were similar to
      respective 6.5 dpp controls. In addition, the relative protein level expression
      ratio of an apoptotic factor, the phosphorylated FADD on Fas, was reduced by 64
      fold in vitrified testes cultured with BMRol+Vit. E. Furthermore, we found in
      this study that the StemPro(r)-34 SFM culture medium supplemented with growth
      factors (e.g. EGF, bFGF, GDNF and LIF) prevented the differentiation of
      spermatogonial stem cells in favor of a significant proliferation with a better
      architectural pattern than in vivo 6.5 dpp controls with an increase of
      seminiferous tubules area for FT (P = 0.0357) and CSF (P = 0.0317). LIMITATIONS
      REASONS FOR CAUTION: Despite our promising results, the evaluation of apoptotic-
      and autophagic-related proteins was studied for a limited amount of proteins and
      on global testicular tissue. WIDER IMPLICATIONS OF THE FINDINGS: The data
      presented herein will help to improve apoptotic and autophagic understanding
      during the first spermatogenic wave. Moreover, our findings illustrate for the
      first time that, using finely-tuned experimental conditions, a testicular in
      vitro culture combined with proteomic technologies may significantly facilitate
      the study of cryopreservation procedures and in vitro culture evaluations. This
      study may also contribute to improve work on testicular tissues from pre-pubertal
      and adolescent cancer survivors. STUDY FUNDING/COMPETING INTEREST(S): This study
      was supported by a Ph.D. grant from the Rouen Normandie Universite and a
      financial support from 'la Ligue nationale contre le cancer' (both awarded to
      L.D.), funding from Institute for Research and Innovation in Biomedicine (IRIB),
      Agence de la Biomedecine, and co-supported by European Union and Region
      Normandie. Europe gets involved in Normandie with European Regional Development
      Fund (ERDF). The authors declare that there is no conflict of interest.

PMID- 29040675
TI  - Fluctuation localization imaging-based fluorescence in situ hybridization
      (fliFISH) for accurate detection and counting of RNA copies in single cells.
AB  - Quantitative gene expression analysis in intact single cells can be achieved
      using single molecule-based fluorescence in situ hybridization (smFISH). This
      approach relies on fluorescence intensity to distinguish between true signals,
      emitted from an RNA copy hybridized with multiple oligonucleotide probes, and
      background noise. Thus, the precision in smFISH is often compromised by partial
      or nonspecific probe binding and tissue autofluorescence, especially when only a
      small number of probes can be fitted to the target transcript. Here we provide an
      accurate approach for setting quantitative thresholds between true and false
      signals, which relies on on-off duty cycles of photoswitchable dyes. This
      fluctuation localization imaging-based FISH (fliFISH) uses on-time fractions
      (measured over a series of exposures) collected from transcripts bound to as low
      as 8 probes, which are distinct from on-time fractions collected from
      nonspecifically bound probes or autofluorescence. Using multicolor fliFISH, we
      identified radial gene expression patterns in mouse pancreatic islets for
      insulin, the transcription factor, NKX2-2 and their ratio (Nkx2-2/Ins2). These
      radial patterns, showing higher values in beta cells at the islet core and lower
      values in peripheral cells, were lost in diabetic mouse islets. In summary,
      fliFISH provides an accurate, quantitative approach for detecting and counting
      true RNA copies and rejecting false signals by their distinct on-time fractions,
      laying the foundation for reliable single-cell transcriptomics.

PMID- 29040676
TI  - Dysbindin promotes progression of pancreatic ductal adenocarcinoma via direct
      activation of PI3K.
AB  - Pancreatic ductal adenocarcinoma (PDAC) represents a biggest challenge in clinic
      oncology due to its invasiveness and lack of targeted therapeutics. Our recent
      study showed that schizophrenia susceptibility factor dysbindin exhibited
      significant higher level in serum of PDAC patients. However, the functional
      relevance of dysbindin in PDAC is still unclear. Here, we show that dysbindin
      promotes tumor growth both in vitro and in vivo by accelerating the G1/S phase
      transition in cell cycle via PI3K/AKT signaling pathway. Mechanistically,
      dysbindin interacts with PI3K and stimulates the kinase activity of PI3K.
      Moreover, overexpression of dysbindin in PDAC is correlated with
      clinicopathological characteristics significantly, such as histological
      differentiation (P = 0.011) and tumor size (P = 0.007). Kaplan-Meier survival
      curves show that patients with high dysbindin expression exhibit poorer overall
      survival, compared to those with low dysbindin expression (P < 0.001).
      Multivariate analysis reveals that dysbindin is an independent prognostic factor
      for pancreatic ductal adenocarcinoma (P = 0.001). Thus, our findings reveal that
      dysbindin is a novel PI3K activator and promotes PDAC progression via stimulation
      of PI3K/AKT. Dysbindin therefore represents a potential target for prognosis and
      therapy of PDAC.

PMID- 29040677
TI  - Navigation-Linked Heads-Up Display in Intracranial Surgery: Early Experience.
AB  - BACKGROUND: The use of intraoperative navigation during microscope cases can be
      limited when attention needs to be divided between the operative field and the
      navigation screens. Heads-up display (HUD), also referred to as augmented
      reality, permits visualization of navigation information during surgery workflow.
      OBJECTIVE: To detail our initial experience with HUD. METHODS: We retrospectively
      reviewed patients who underwent HUD-assisted surgery from April 2016 through
      April 2017. All lesions were assessed for accuracy and those from the latter half
      of the study were assessed for utility. RESULTS: Seventy-nine patients with 84
      pathologies were included. Pathologies included aneurysms (14), arteriovenous
      malformations (6), cavernous malformations (5), intracranial stenosis (3),
      meningiomas (27), metastasis (4), craniopharygniomas (4), gliomas (4),
      schwannomas (3), epidermoid/dermoids (3), pituitary adenomas (2) hemangioblastoma
      (2), choroid plexus papilloma (1), lymphoma (1), osteoblastoma (1), clival
      chordoma (1), cerebrospinal fluid leak (1), abscess (1), and a cerebellopontine
      angle Teflon granuloma (1). Fifty-nine lesions were deep and 25 were superficial.
      Structures identified included the lesion (81), vessels (48), and nerves/brain
      tissue (31). Accuracy was deemed excellent (71.4%), good (20.2%), or poor (8.3%).
      Deep lesions were less likely to have excellent accuracy (P = .029). HUD was used
      during bed/head positioning (50.0%), skin incision (17.3%), craniotomy (23.1%),
      dural opening (26.9%), corticectomy (13.5%), arachnoid opening (36.5%), and
      intracranial drilling (13.5%). HUD was deactivated at some point during the
      surgery in 59.6% of cases. There were no complications related to HUD use.
      CONCLUSION: HUD can be safely used for a wide variety of vascular and oncologic
      intracranial pathologies and can be utilized during multiple stages of surgery.

PMID- 29040679
TI  - 2'-Fluoroarabinonucleic acid modification traps G-quadruplex and i-motif
      structures in human telomeric DNA.

PMID- 29040678
TI  - Extended models for nosocomial infection: parameter estimation and model
      selection.
AB  - We consider extensions to previous models for patient level nosocomial infection
      in several ways, provide a specification of the likelihoods for these new models,
      specify new update steps required for stochastic integration, and provide
      programs that implement these methods to obtain parameter estimates and model
      choice statistics. Previous susceptible-infected models are extended to allow for
      a latent period between initial exposure to the pathogen and the patient becoming
      themselves infectious, and the possibility of decolonization. We allow for
      multiple facilities, such as acute care hospitals or long-term care facilities
      and nursing homes, and for multiple units or wards within a facility. Patient
      transfers between units and facilities are tracked and accounted for in the
      models so that direct importation of a colonized individual from one facility or
      unit to another might be inferred. We allow for constant transmission rates,
      rates that depend on the number of colonized individuals in a unit or facility,
      or rates that depend on the proportion of colonized individuals. Statistical
      analysis is done in a Bayesian framework using Markov chain Monte Carlo methods
      to obtain a sample of parameter values from their joint posterior distribution.
      Cross validation, deviance information criterion and widely applicable
      information criterion approaches to model choice fit very naturally into this
      framework and we have implemented all three. We illustrate our methods by
      considering model selection issues and parameter estimation for data on
      methicilin-resistant Staphylococcus aureus surveillance tests over 1 year at a
      Veterans Administration hospital comprising seven wards.

PMID- 29040680
TI  - Variable Levels of Resistance of Soybean Genotypes on the Performance of
      Euschistus heros (Hemiptera: Pentatomidae).
AB  - The Neotropical brown stink bug Euschistus heros (Fabr.) (Hemiptera:
      Pentatomidae) is one of the major soybean pests in South America. This species is
      responsible for high levels of infestation, causes critical damage to seeds, it
      is associated with leaf retention on plants, and it is extremely difficult to
      manage. Host plant resistance is a notable technique to assist in reducing the
      stink bug population in soybean crops. The antibiosis resistance of soybean
      genotypes to E. heros was evaluated in laboratory. Genotypes L1-1-01, 'IAC 100',
      'IAC 23', and 'Coodetec 208' increased the length of nymphal developmental time.
      PI 274453 and PI 227687 reduced egg viability and also adult body weight. PI
      274454, 'IAC 19', PI 227687, and PI 229358 led to low nymphal viability. These
      results suggest that these genotypes may be useful in soybean breeding programs
      that focus on the development of genotypes resistant to E. heros.

PMID- 29040681
TI  - 20 years of the SMART protein domain annotation resource.
AB  - SMART (Simple Modular Architecture Research Tool) is a web resource
      (http://smart.embl.de) for the identification and annotation of protein domains
      and the analysis of protein domain architectures. SMART version 8 contains
      manually curated models for more than 1300 protein domains, with approximately
      100 new models added since our last update article (1). The underlying protein
      databases were synchronized with UniProt (2), Ensembl (3) and STRING (4),
      doubling the total number of annotated domains and other protein features to more
      than 200 million. In its 20th year, the SMART analysis results pages have been
      streamlined again and its information sources have been updated. SMART's vector
      based display engine has been extended to all protein schematics in SMART and
      rewritten to use the latest web technologies. The internal full text search
      engine has been redesigned and updated, resulting in greatly increased search
      speed.

PMID- 29040682
TI  - Dose-response curves for analyzing of dicentric chromosomes and chromosome
      translocations following doses of 1000 mGy or less, based on irradiated
      peripheral blood samples from five healthy individuals.
AB  - In terms of biological dosimetry at the time of radiation exposure, the dicentric
      chromosome (Dic) assay (DCA) is the gold standard for assessing for the acute
      phase and chromosome translocation (Tr) analysis is the gold standard for
      assessing the chronic phase. It is desirable to have individual dose-response
      curves (DRCs) for each laboratory because the analysis criteria differ between
      laboratories. We constructed the DRCs for radiation dose estimation (with three
      methods) using peripheral blood (PB) samples from five healthy individuals.
      Aliquots were irradiated with one of eight gamma-ray doses (0, 10, 20, 50, 100,
      200, 500 or 1000 mGy), then cultured for 48 h. The number of chromosome
      aberrations (CAs) was analyzed by DCA, using Giemsa staining and centromere
      fluorescence in situ hybridization (centromere-FISH) and by chromosome painting
      (chromosome pairs 1, 2 and 4) for Tr analysis. In DCA, there was large variation
      between individuals in the frequency of Dics formed, and the slopes of the DRCs
      were different. In Tr analysis, although variation was observed in the frequency
      of Tr, the slopes of the DRCs were similar after adjusting the background for
      age. Good correlation between the irradiation dose and the frequency of CAs
      formed was observed with these three DRCs. However, performing three different
      biological dosimetry assays simultaneously on PB from five donors nonetheless
      results in variation in the frequency of CAs formed, especially at doses of 50
      mGy or less, highlighting the difficulty of biological dosimetry using these
      methods. We conclude that it might be difficult to construct universal DRCs.

PMID- 29040684
TI  - Multimodality Treatment of Skull Base Chondrosarcomas: The Role of Histology
      Specific Treatment Protocols.

PMID- 29040683
TI  - Quantitating translational control: mRNA abundance-dependent and independent
      contributions and the mRNA sequences that specify them.
AB  - Translation rate per mRNA molecule correlates positively with mRNA abundance. As
      a result, protein levels do not scale linearly with mRNA levels, but instead
      scale with the abundance of mRNA raised to the power of an 'amplification
      exponent'. Here we show that to quantitate translational control, the translation
      rate must be decomposed into two components. One, TRmD, depends on the mRNA level
      and defines the amplification exponent. The other, TRmIND, is independent of mRNA
      amount and impacts the correlation coefficient between protein and mRNA levels.
      We show that in Saccharomyces cerevisiae TRmD represents ~20% of the variance in
      translation and directs an amplification exponent of 1.20 with a 95% confidence
      interval [1.14, 1.26]. TRmIND constitutes the remaining ~80% of the variance in
      translation and explains ~5% of the variance in protein expression. We also find
      that TRmD and TRmIND are preferentially determined by different mRNA sequence
      features: TRmIND by the length of the open reading frame and TRmD both by a ~60
      nucleotide element that spans the initiating AUG and by codon and amino acid
      frequency. Our work provides more appropriate estimates of translational control
      and implies that TRmIND is under different evolutionary selective pressures than
      TRmD.

PMID- 29040685
TI  - A pooled analysis of dietary sugar/carbohydrate intake and esophageal and gastric
      cardia adenocarcinoma incidence and survival in the USA.
AB  - Background: During the past 40 years, esophageal/gastric cardia adenocarcinoma
      (EA/GCA) incidence increased in Westernized countries, but survival remained low.
      A parallel increase in sugar intake, which may facilitate carcinogenesis by
      promoting hyperglycaemia, led us to examine sugar/carbohydrate intake in
      association with EA/GCA incidence and survival. Methods: We pooled 500 EA cases,
      529 GCA cases and 2027 controls from two US population-based case-control studies
      with cases followed for vital status. Dietary intake, assessed by study-specific
      food frequency questionnaires, was harmonized and pooled to estimate 12 measures
      of sugar/carbohydrate intake. Multivariable-adjusted odds ratios (ORs) and hazard
      ratios [95% confidence intervals (CIs)] were calculated using multinomial
      logistic regression and Cox proportional hazards regression, respectively.
      Results: EA incidence was increased by 51-58% in association with sucrose
      (ORQ5vs.Q1 = 1.51, 95% CI = 1.01-2.27), sweetened desserts/beverages (ORQ5vs.Q1 =
      1.55, 95% CI = 1.06-2.27) and the dietary glycaemic index (ORQ5vs.Q1 = 1.58, 95%
      CI = 1.13-2.21). Body mass index (BMI) and gastro-esophageal reflux disease
      (GERD) modified these associations (Pmultiplicative-interaction <= 0.05). For
      associations with sucrose and sweetened desserts/beverages, respectively, the OR
      was elevated for BMI < 25 (ORQ4-5vs.Q1-3 = 1.79, 95% CI = 1.26-2.56 and ORQ4
      5vs.Q1-3 = 1.45, 95% CI = 1.03-2.06), but not BMI >= 25 (ORQ4-5vs.Q1-3 = 1.05,
      95% CI = 0.76-1.44 and ORQ4-5vs.Q1-3 = 0.85, 95% CI = 0.62-1.16). The EA
      glycaemic index association was elevated for BMI >= 25 (ORQ4-5vs.Q1-3 = 1.38, 95%
      CI = 1.03-1.85), but not BMI < 25 (ORQ4-5vs.Q1-3 = 0.88, 95% CI = 0.62-1.24). The
      sucrose-EA association OR for GERD < weekly was 1.58 (95% CI = 1.16-2.14), but
      for GERD >= weekly was 1.01 (95% CI = 0.70-1.47). Sugar/carbohydrate measures
      were not associated with GCA incidence or EA/GCA survival. Conclusions: If
      confirmed, limiting intake of sucrose (e.g. table sugar), sweetened
      desserts/beverages, and foods that contribute to a high glycaemic index, may be
      plausible EA risk reduction strategies.

PMID- 29040686
TI  - The World Health Organization's Response to Emerging Human Immunodeficiency Virus
      Drug Resistance and a Call for Global Action.
AB  - The global community, including the World Health Organization (WHO), has
      committed to ending the AIDS epidemic and to ensuring that 90% of people living
      with human immunodeficiency virus (HIV) are diagnosed, 90% start treatment, and
      90% achieve and maintain virological suppression. The emergence of HIV drug
      resistance (HIVDR) as antiretroviral treatment programs expand could preclude the
      90-90-90 targets adopted by the United Nations General Assembly at the High-Level
      Meeting on Ending AIDS from being achieved. The Global Action Plan on HIVDR is a
      call for collective action grounded on normative guidance providing a
      standardized and robust approach to monitoring, preventing, and responding to
      HIVDR over the next 5 years (2017-2021). WHO is committed to supporting country,
      global, regional, and national partners to implement and monitor the progress of
      the Global Action Plan. This article outlines the key components of WHO's
      strategy to tackle HIVDR and the role the organization takes in leading the
      global response to HIVDR.

PMID- 29040687
TI  - Mortality risk in patients on hemodiafiltration versus hemodialysis: a 'real
      world' comparison from the DOPPS.
AB  - Background: With its convective component, hemodiafiltration (HDF) provides
      better middle molecule clearance compared with hemodialysis (HD) and is
      postulated to improve survival. A previous analysis of Dialysis Outcomes and
      Practice Patterns Study (DOPPS) data in 1998-2001 found lower mortality rates for
      high replacement fluid volume HDF versus HD. Randomized controlled trials have
      not shown uniform survival advantage for HDF; in secondary (non-randomized)
      analyses, better outcomes were observed in patients receiving the highest
      convection volumes. Methods: In a 'real-world' setting, we analyzed patients on
      dialysis >90 days from seven European countries in DOPPS Phases 4 and 5 (2009
      15). Adjusted Cox regression was used to study HDF (versus HD) and mortality,
      overall and by replacement fluid volume. Results: Among 8567 eligible patients,
      2012 (23%) were on HDF, ranging from 42% in Sweden to 12% in Germany. Median
      follow-up was 1.5 years during which 1988 patients died. The adjusted mortality
      hazard ratio (95% confidence interval) was 1.14 (1.00-1.29) for any HDF versus HD
      and 1.08 (0.92-1.28) for HDF >20 L replacement fluid volume versus HD. Similar
      results were found for cardiovascular and infection-related mortality. In an
      additional analysis aiming to avoid treatment-by-indication bias, we did not
      observe lower mortality rates in facilities using more HDF (versus HD).
      Conclusions: Our results do not support the notion that HDF provides superior
      patient survival. Further trials designed to test the effect of high-volume HDF
      (versus lower volume HDF versus HD) on clinical outcomes are needed to adequately
      inform clinical practices.

PMID- 29040688
TI  - The online Tabloid Proteome: an annotated database of protein associations.
AB  - A complete knowledge of the proteome can only be attained by determining the
      associations between proteins, along with the nature of these associations (e.g.
      physical contact in protein-protein interactions, participation in complex
      formation or different roles in the same pathway). Despite extensive efforts in
      elucidating direct protein interactions, our knowledge on the complete spectrum
      of protein associations remains limited. We therefore developed a new approach
      that detects protein associations from identifications obtained after re
      processing of large-scale, public mass spectrometry-based proteomics data. Our
      approach infers protein association based on the co-occurrence of proteins across
      many different proteomics experiments, and provides information that is almost
      completely complementary to traditional direct protein interaction studies. We
      here present a web interface to query and explore the associations derived from
      this method, called the online Tabloid Proteome. The online Tabloid Proteome also
      integrates biological knowledge from several existing resources to annotate our
      derived protein associations. The online Tabloid Proteome is freely available
      through a user-friendly web interface, which provides intuitive navigation and
      data exploration options for the user at http://iomics.ugent.be/tabloidproteome.

PMID- 29040690
TI  - In memory of Professor Takeo Ohnishi.

PMID- 29040689
TI  - Regulatory dynamics in the ternary DnaA complex for initiation of chromosomal
      replication in Escherichia coli.
AB  - In Escherichia coli, the level of the ATP-DnaA initiator is increased temporarily
      at the time of replication initiation. The replication origin, oriC, contains a
      duplex-unwinding element (DUE) flanking a DnaA-oligomerization region (DOR),
      which includes twelve DnaA-binding sites (DnaA boxes) and the DNA-bending protein
      IHF-binding site (IBS). Although complexes of IHF and ATP-DnaA assembly on the
      DOR unwind the DUE, the configuration of the crucial nucleoprotein complexes
      remains elusive. To resolve this, we analyzed individual DnaA protomers in the
      complex and here demonstrate that the DUE-DnaA-box-R1-IBS-DnaA-box-R5M region is
      essential for DUE unwinding. R5M-bound ATP-DnaA predominantly promotes ATP-DnaA
      assembly on the DUE-proximal DOR, and R1-bound DnaA has a supporting role. This
      mechanism might support timely assembly of ATP-DnaA on oriC. DnaA protomers bound
      to R1 and R5M directly bind to the unwound DUE strand, which is crucial in
      replication initiation. Data from in vivo experiments support these results. We
      propose that the DnaA assembly on the IHF-bent DOR directly binds to the unwound
      DUE strand, and timely formation of this ternary complex regulates replication
      initiation. Structural features of oriC support the idea that these mechanisms
      for DUE unwinding are fundamentally conserved in various bacterial species
      including pathogens.

PMID- 29040691
TI  - Differential Growth Rates of Benign vs. Malignant Thyroid Nodules.
AB  - Context: Thyroid nodule growth was once considered concerning for malignancy, but
      data showing that benign nodules grow questioned the use of this paradigm. To
      date, however, no studies have adequately evaluated whether growth rates differ
      in malignant vs. benign nodules. Objective: To sonographically evaluate growth
      rates in benign and malignant thyroid nodules >=1 cm. Design: Prospective, cohort
      study of patients with tissue diagnosis of benign or malignant disease, with
      repeated ultrasound evaluation six or more months apart. Main Outcomes: Growth
      rate in largest dimension of malignant compared with benign thyroid nodules.
      Regression models were used to evaluate predictors of growth. Results: Malignant
      nodules (126) met inclusion criteria (>=6-month nonoperative followup) and were
      compared with 1363 benign nodules. Malignant nodules were not found to be
      uniquely selected or prospectively observed solely for low-risk phenotype. Median
      ultrasound intervals were similar (21.8 months for benign nodules; 20.9 months
      for malignant nodules). Malignant nodules were more likely to grow >2 mm/y
      compared with benign nodules [relative risk (RR) = 2.5, 95% confidence interval
      (CI), 1.6 to 3.1; P < 0.001], which remained true after adjustment for clinical
      factors. The RR of a nodule being malignant increased with faster growth rates.
      Malignant nodules growing >2 mm/y had greater odds of being more aggressive
      cancers [intermediate risk: odds ratio (OR) = 2.99; 95% CI, 1.20 to 7.47; P =
      0.03; higher risk: OR = 8.69; 95% CI, 1.78 to 42.34; P = 0.02]. Conclusions:
      Malignant nodules, especially higher-risk phenotypes, grow faster than benign
      nodules. As growth >2 mm/y predicts malignant compared with benign disease, this
      clinical parameter can contribute to the assessment of thyroid cancer risk.

PMID- 29040692
TI  - RMBase v2.0: deciphering the map of RNA modifications from epitranscriptome
      sequencing data.
AB  - More than 100 distinct chemical modifications to RNA have been characterized so
      far. However, the prevalence, mechanisms and functions of various RNA
      modifications remain largely unknown. To provide transcriptome-wide landscapes of
      RNA modifications, we developed the RMBase v2.0 (http://rna.sysu.edu.cn/rmbase/),
      which is a comprehensive database that integrates epitranscriptome sequencing
      data for the exploration of post-transcriptional modifications of RNAs and their
      relationships with miRNA binding events, disease-related single-nucleotide
      polymorphisms (SNPs) and RNA-binding proteins (RBPs). RMBase v2.0 was expanded
      with ~600 datasets and ~1 397 000 modification sites from 47 studies among 13
      species, which represents an approximately 10-fold expansion when compared with
      the previous release. It contains ~1 373 000 N6-methyladenosines (m6A), ~5400 N1
      methyladenosines (m1A), ~9600 pseudouridine (Psi) modifications, ~1000 5
      methylcytosine (m5C) modifications, ~5100 2'-O-methylations (2'-O-Me), and ~2800
      modifications of other modification types. Moreover, we built a new module called
      'Motif' that provides the visualized logos and position weight matrices (PWMs) of
      the modification motifs. We also constructed a novel module termed 'modRBP' to
      study the relationships between RNA modifications and RBPs. Additionally, we
      developed a novel web-based tool named 'modMetagene' to plot the metagenes of RNA
      modification along a transcript model. This database will help researchers
      investigate the potential functions and mechanisms of RNA modifications.

PMID- 29040693
TI  - AmyPro: a database of proteins with validated amyloidogenic regions.
AB  - Soluble functional proteins may transform into insoluble amyloid fibrils that
      deposit in a variety of tissues. Amyloid formation is a hallmark of age-related
      degenerative disorders. Perhaps surprisingly, amyloid fibrils can also be
      beneficial and are frequently exploited for diverse functional roles in
      organisms. Here we introduce AmyPro, an open-access database providing a
      comprehensive, carefully curated collection of validated amyloid fibril-forming
      proteins from all kingdoms of life classified into broad functional categories
      (http://amypro.net). In particular, AmyPro provides the boundaries of
      experimentally validated amyloidogenic sequence regions, short descriptions of
      the functional relevance of the proteins and their amyloid state, a list of the
      experimental techniques applied to study the amyloid state, important
      structural/functional/variation/mutation data transferred from UniProt, a list of
      relevant PDB structures categorized according to protein states, database cross
      references and literature references. AmyPro greatly improves on similar
      currently available resources by incorporating both prions and functional
      amyloids in addition to pathogenic amyloids, and allows users to screen their
      sequences against the entire collection of validated amyloidogenic sequence
      fragments. By enabling further elucidation of the sequential determinants of
      amyloid fibril formation, we hope AmyPro will enhance the development of new
      methods for the precise prediction of amyloidogenic regions within proteins.

PMID- 29040695
TI  - Intracranial Bypass of Posterior Inferior Cerebellar Artery Aneurysms.

PMID- 29040694
TI  - LBD14/ASL17 Positively Regulates Lateral Root Formation and is Involved in ABA
      Response for Root Architecture in Arabidopsis.
AB  - The LATERAL ORGAN BOUNDARIES (LOB) DOMAIN/ASYMMETRIC LEAVES2-LIKE (LBD/ASL) gene
      family members play key roles in diverse aspects of plant development. Previous
      studies have shown that LBD16, 18, 29 and 33 are critical for integrating the
      plant hormone auxin to control lateral root development in Arabidopsis thaliana.
      In the present study, we show that LBD14 is expressed exclusively in the root
      where it promotes lateral root (LR) emergence. Repression of LBD14 expression by
      ABA correlates with the inhibitory effects of ABA on LR emergence. Transient gene
      expression assays with Arabidopsis protoplasts demonstrated that LBD14 is a
      nuclear-localized transcriptional activator. The knock-down of LBD14 expression
      by RNA interference (RNAi) resulted in reduced LR formation by delaying both LR
      primordium development and LR emergence, whereas overexpression of LBD14 in
      Arabidopsis enhances LR formation. We show that ABA (but not other plant hormones
      such as auxin, brassinosteroids and cytokinin) specifically down-regulated beta
      glucuronidase (GUS) expression under the control of the LBD14 promoter in
      transgenic Arabidopsis during LR development from initiation to emergence and
      endogenous LBD14 transcript levels in the root. Moreover, RNAi of LBD14 enhanced
      the LR suppression in response to ABA, whereas LBD14 overexpression did not alter
      the ABA-mediated suppression of LR formation. Taken together, these results
      suggest that LBD14 promoting LR formation is one of the critical factors
      regulated by ABA to inhibit LR growth, contributing to the regulation of the
      Arabidopsis root system architecture in response to ABA.

PMID- 29040696
TI  - The Effect of Surgical Start Time on Complications Associated With Neurological
      Surgeries.
AB  - BACKGROUND: Neurosurgical procedures are necessary at all times of day. Other
      surgical specialties have examined the effect of surgical start time (SST) on
      morbidity and mortality; however, a similar study has not been performed for
      neurosurgical procedures. OBJECTIVE: To perform a retrospective cohort study
      describing the association between SST and operative morbidity. METHODS: We
      analyzed all patients undergoing neurological surgery between January 1, 2007 and
      August 1, 2014 at our institution. This study included 15 807 patients. A total
      of 785 complications were identified through the self-reported morbidity and
      mortality reports created by faculty and resident neurosurgeons. We used
      multilevel logistic regression to investigate the association of SST with
      morbidity. RESULTS: In multilevel logistic regression, our Baseline model
      demonstrated that the odds of complication increased by more than 50% for start
      times between 21:01 and 07:00 (odds ratio [OR] 1.53, 95% confidence interval [CI]
      1.03-2.29, P = .04). When accounting for the length of the surgery, the odds of a
      complication were even greater for later time periods 21:01 to 07:00 (OR 2.16,
      95% CI 1.44-3.23, P < .001). The only statistically significant factor that
      predicted severity of the complication was if the operation was emergent compared
      to elective (OR 1.70, 95% CI 1.11-2.60, P = .02). An SST between 21:01 and 07:00
      substantially contributed when severe complications were isolated (OR 1.61, 95%
      CI 1.50-2.90, P = .08). CONCLUSION: Patients with SSTs between 21:01 and 07:00
      are at an increased risk of developing morbidity compared to patients with an SST
      earlier in the day.

PMID- 29040697
TI  - Mapping Selection within Drosophila melanogaster Embryo's Anatomy.
AB  - We present a survey of selection across Drosophila melanogaster embryonic
      anatomy. Our approach integrates genomic variation, spatial gene expression
      patterns, and development with the aim of mapping adaptation over the entire
      embryo's anatomy. Our adaptation map is based on analyzing spatial gene
      expression information for 5,969 genes (from text-based annotations of in situ
      hybridization data directly from the BDGP database, Tomancak et al. 2007) and the
      polymorphism and divergence in these genes (from the project DGRP, Mackay et al.
      2012).The proportion of nonsynonymous substitutions that are adaptive, neutral,
      or slightly deleterious are estimated for the set of genes expressed in each
      embryonic anatomical structure using the distribution of fitness effects-alpha
      method (Eyre-Walker and Keightley 2009). This method is a robust derivative of
      the McDonald and Kreitman test (McDonald and Kreitman 1991). We also explore
      whether different anatomical structures differ in the phylogenetic age, codon
      usage, or expression bias of the genes they express and whether genes expressed
      in many anatomical structures show more adaptive substitutions than other
      genes.We found that: 1) most of the digestive system and ectoderm-derived
      structures are under selective constraint, 2) the germ line and some specific
      mesoderm-derived structures show high rates of adaptive substitution, and 3) the
      genes that are expressed in a small number of anatomical structures show higher
      expression bias, lower phylogenetic ages, and less constraint.

PMID- 29040698
TI  - Clinical Outcome after Endoscopic Endonasal Resection of Tuberculum Sella
      Meningiomas.
AB  - BACKGROUND: In select cases, the endoscopic endonasal approach (EEA) has distinct
      advantages for resection of tuberculum sella meningiomas (TSM). OBJECTIVE: To
      report the extent of resection (EOR), complication rates, and outcomes in a large
      series of TSM treated by the EEA. METHODS: Twenty-five consecutive TSM cases
      treated by EEA from 2008 to 2016 were retrospectively reviewed. Patient history,
      imaging, volumetric EOR, complications, and outcomes are presented. RESULTS: Mean
      patient age was 53.9 yr, with female predominance (84%). Preoperatively, 84% of
      patients had vision impairment and 68% had optic canal tumor invasion. The tumor
      was abutting or partially encasing the anterior cerebral artery in 14 (56%) and 3
      (12%) patients, respectively. The supraclinoid internal carotid artery (ICA) was
      partially or completely encased in 4 (16%) and 4 (16%) patients, respectively.
      Gross total resection (GTR) was achieved in 19/25 (76%) cases. Complete ICA
      encasement was the most common reason for subtotal resection. Among patients
      without complete ICA encasement, GTR was achieved in 19/20 (95%) patients. Optic
      canal invasion, tumor volume, intratumoral calcifications, and partial vascular
      encasement were not limiting factors for GTR. Eighty-eight percent of patients
      with preoperative visual impairment had improvement or normalization of vision.
      No patient experienced permanent visual deterioration or new permanent pituitary
      dysfunction. Cerebrospinal fluid leakage occurred in 2 (8%) cases. CONCLUSION:
      The EEA for resection of TSM provides high rates of GTR and visual improvement
      with a low rate of complications. Direct contact or partial encasement of the ICA
      and anterior cerebral artery does not limit the EOR.

PMID- 29040699
TI  - Letter: Simple Preoperative Patient-Reported Factors Predict Adverse Outcome
      After Elective Cranial Neurosurgery.

PMID- 29040700
TI  - Radiation-Induced Changes After Stereotactic Radiosurgery for Brain Arteriovenous
      Malformations: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Radiation-induced changes (RICs) are the most common complication of
      stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVMs), and
      they appear as perinidal T2-weighted hyperintensities on magnetic resonance
      imaging, with or without associated neurological symptoms. OBJECTIVE: To
      determine the rates of RIC after AVM SRS and identify risk factors. METHODS: A
      literature review was performed using PubMed and MEDLINE to identify studies
      reporting RIC in AVM patients treated with SRS. RICs were classified as
      radiologic (any neuroimaging evidence), symptomatic (any associated neurological
      deterioration, regardless of duration), and permanent (neurological decline
      without recovery). Baseline, treatment, and outcomes data were extracted for
      statistical analysis. RESULTS: Based on pooled data from 51 studies, the overall
      rates of radiologic, symptomatic, and permanent RIC after AVM SRS were 35.5%
      (1143/3222 patients, 32 studies), 9.2% (499/5447 patients, 46 studies), and 3.8%
      (202/5272 patients, 39 studies), respectively. Radiologic RIC was significantly
      associated with lack of prior AVM rupture (odds ratio [OR] = 0.57; 95% confidence
      interval [CI]: 0.47-0.69; P < .001) and treatment with repeat SRS (OR = 6.19; 95%
      CI: 2.42-15.85; P < .001). Symptomatic RIC was significantly associated with deep
      AVM location (OR = 0.38; 95% CI: 0.21-0.67; P < .001). CONCLUSION: Approximately
      1 in 3 patients with AVMs treated with SRS develop radiologically evident RIC,
      and of those with radiologic RIC, 1 in 4 develop neurological symptoms. Lack of
      prior AVM hemorrhage and repeat SRS are risk factors for radiologic RIC, and deep
      nidus location is a risk factor for symptomatic RIC.

PMID- 29040701
TI  - Comparison of glomerular filtration rate estimating equations derived from
      creatinine and cystatin C: validation in the Age, Gene/Environment Susceptibility
      Reykjavik elderly cohort.
AB  - Background: Validation studies comparing glomerular filtration rate (GFR)
      equations based on standardized creatinine and cystatin C assays in the elderly
      are needed. The Icelandic Age, Gene/Environment Susceptibility-Kidney cohort was
      used to compare two pairs of recently developed GFR equations, the revised Lund
      Malmo creatinine equation (LMRCr) and the arithmetic mean of the LMRCr and
      Caucasian, Asian, Paediatric and Adult cystatin C equations (MEANLMR+CAPA), as
      well as the Full Age Spectrum creatinine equation (FASCr) and its combination
      with cystatin C (FASCr+Cys), with the corresponding pair of Chronic Kidney
      Disease Epidemiology Collaboration equations (CKD-EPICr and CKD-EPICr+Cys).
      Methods: A total of 805 individuals, 74-93 years of age, underwent measurement of
      GFR (mGFR) using plasma clearance of iohexol. Four metrics were used to compare
      the performance of the GFR equations: bias, precision, accuracy [including the
      percentage of participants with estimated GFR (eGFR) within 30% of mGFR (P30)]
      and the ability to detect mGFR <60 mL/min/1.73 m2. Results: All equations had a
      P30 >90%. LMRCr and FASCr yielded significantly higher precision and P30 than CKD
      EPICr, while bias was significantly worse. LMRCr, FASCr and CKD-EPICr showed
      similar ability to detect mGFR <60 mL/min/1.73 m2 based on the area under the
      receiver operating characteristic curves. MEANLMR+CAPA, FASCr+Cys and CKD
      EPICr+Cys all exhibited consistent improvements compared with the corresponding
      creatinine-based equations. Conclusion: None of the creatinine-based equations
      was clearly superior overall in this community-dwelling elderly cohort. The
      addition of cystatin C improved all of the creatinine-based equations.

PMID- 29040702
TI  - Literacy Outcomes in Deaf Students with Cochlear Implants: Current State of the
      Knowledge.
AB  - The purpose of this paper is to examine the available peer-reviewed research
      regarding literacy achievement in deaf children with cochlear implants. A related
      goal is to identify gaps in the empirical literature and suggest directions for
      future research. Included in this review are studies that exclusively report
      reading and writing outcomes for groups of students. A total of 21 studies were
      identified, representing those published over approximately a 20-year time period
      (1997-2016) and collectively reporting the literacy outcomes for over 1,000
      cochlear implant users. Overall findings of the studies of reading comprehension
      suggest that the majority of participants achieved scores in the average range,
      although a wide-range of variability was reported. Only 3 studies of writing were
      available for review, with 2 reporting lower achievement in this area as compared
      to reading. Factors impacting outcomes achieved such as age at implantation,
      presence of additional disabilities, consistency of device use, and communication
      modality are explored and summarized.

PMID- 29040704
TI  - In Planta Processing of the SpCas9-gRNA Complex.
AB  - In CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat/CRISPR
      associated protein 9)-mediated genome editing in plants, Streptococcus pyogenes
      Cas9 (SpCas9) protein and the required guide RNA (gRNA) are, in most cases,
      expressed from a stably integrated transgene. Generally, SpCas9 protein is
      expressed from an RNA polymerase (pol) II promoter, while gRNA is expressed from
      a pol III promoter. However, pol III promoters have not been much characterized
      other than in model plants, making it difficult to select appropriate promoters
      for specific applications, while pol II transcripts have to be processed to
      generate functional gRNAs. Recently, successful processing of a pol II transcript
      into functional gRNAs using ribozyme or Csy4-RNA cleavage systems has been
      demonstrated. Here, we show that functional gRNAs can be efficiently processed
      using SpCas9 protein and plant endogenous RNA cleavage systems without the need
      for a specific RNA processing system. In our system, SpCas9 RNA and gRNA are both
      transcribed as a single RNA using a single pol II promoter; translated SpCas9
      protein can be bound to this RNA and, finally, extra RNA sequences are trimmed by
      plant RNA processing systems to form a functional SpCas9-gRNA complex. The
      efficiency of targeted mutagenesis using our novel SpCas9-gRNA fused system was
      comparable with that of the SpCas9-gRNA system with ribozyme sequence, achieving
      rates of up to 100% in rice. Our results could be useful in developing stable
      SpCas9-gRNA expression systems and in RNA virus vector-mediated genome editing
      systems in plants.

PMID- 29040705
TI  - The MRPP1/MRPP2 complex is a tRNA-maturation platform in human mitochondria.
AB  - Mitochondrial polycistronic transcripts are extensively processed to give rise to
      functional mRNAs, rRNAs and tRNAs; starting with the release of tRNA elements
      through 5'-processing by RNase P (MRPP1/2/3-complex) and 3'-processing by RNase Z
      (ELAC2). Here, we show using in vitro experiments that MRPP1/2 is not only a
      component of the mitochondrial RNase P but that it retains the tRNA product from
      the 5'-processing step and significantly enhances the efficiency of ELAC2
      catalyzed 3'-processing for 17 of the 22 tRNAs encoded in the human mitochondrial
      genome. Furthermore, MRPP1/2 retains the tRNA product after ELAC2 processing and
      presents the nascent tRNA to the mitochondrial CCA-adding enzyme. Thus, in
      addition to being an essential component of the RNase P reaction, MRPP1/2 serves
      as a processing platform for several down-stream tRNA maturation steps in human
      mitochondria. These findings are of fundamental importance for our molecular
      understanding of disease-related mutations in MRPP1/2, ELAC2 and mitochondrial
      tRNA genes.

PMID- 29040703
TI  - Evidence and context of use for contrast enhancement as a surrogate of disease
      burden and treatment response in malignant glioma.
AB  - The use of contrast enhancement within the brain on CT or MRI has been the gold
      standard for diagnosis and therapeutic response assessment in malignant gliomas
      for decades. The use of contrast enhancing tumor size, however, remains
      controversial as a tool for accurately diagnosing and assessing treatment
      efficacy in malignant gliomas, particularly in the current, quickly evolving
      therapeutic landscape. The current article consolidates overwhelming evidence
      from hundreds of studies in the field of neuro-oncology, providing the necessary
      evidence base and specific contexts of use for consideration of contrast
      enhancing tumor size as an appropriate surrogate biomarker for disease burden and
      as a tool for measuring treatment response in malignant glioma, including
      glioblastoma.

PMID- 29040706
TI  - Inhibition of survivin expression after using oxaliplatin and vinflunine to
      induce cytogenetic damage in vitro in lymphocytes from colon cancer patients and
      healthy individuals.
AB  - Chemotherapy drugs usually inflict a lethal dose to tumour cells with the
      consequence that these cells are being killed by cell death. However, each round
      of chemotherapy also causes damage to normal somatic cells. The DNA cross-linking
      agent oxaliplatin (OXP), which causes DNA double-strand breaks, and vinflunine
      (VFN), which disrupts the mitotic spindle, are two of these chemotherapy drugs
      which were evaluated in vitro using peripheral lymphocytes from colorectal cancer
      patients and healthy individuals to determine any differential response.
      Endpoints examined included micronucleus (MN) induction using the cytokinesis
      blocked micronucleus (CBMN) assay and pancentromeric fluorescence in situ
      hybridisation. Also, survivin expression was monitored since it regulates the
      mitotic spindle checkpoint and inhibits apoptosis. OXP produced cytogenetic
      damage (micronuclei in binucleated cells) via its clastogenic but also previously
      unknown aneugenic action, possibly through interfering with topoisomerase II,
      whilst VFN produced micronuclei in mononucleated cells because of incomplete
      karyokinesis. Survivin expression was found to be significantly reduced in a
      concentration-dependent manner by not only OXP but surprisingly also VFN. This
      resulted in large numbers of multinucleated cells found with the CBMN assay. As
      survivin is upregulated in cancers, eliminating apoptosis inhibition might
      provide a more targeted chemotherapy approach; particularly, when considering
      VFN, which only affects cycling cells by inhibiting their mitotic spindle, and
      alongside possibly other pro-apoptotic compounds. Hence, these newly found
      properties of VFN -the inhibition of survivin expression-might demonstrate a
      promising chemotherapeutic approach as VFN induces less DNA damage in normal
      somatic cells compared to other chemotherapeutic compounds.

PMID- 29040707
TI  - Effective Radiation Dose in the Wrist Resulting from a Radiographic Device, Two
      CBCT Devices and One MSCT Device: A Comparative Study.
AB  - The objective of the present study was to assess and compare the effective doses
      in the wrist region resulting from conventional radiography device, multislice
      computed tomography (MSCT) device and two cone beam computed tomography (CBCT)
      devices using MOSFET dosemeters and a custom made anthropomorphic RANDO phantom
      according to the ICRP 103 recommendation. The effective dose for the conventional
      radiography was 1.0 MUSv. The effective doses for the NewTom 5 G CBCT ranged
      between 0.7 MUSv and 1.6 MUSv, for the Planmed Verity CBCT 2.4 MUSv and for the
      MSCT 8.6 MUSv. When compared with the effective dose for AP- and LAT projections
      of a conventional radiographic device, this study showed an 8.6-fold effective
      dose for standard MSCT protocol and between 0.7 and 2.4-fold effective dose for
      standard CBCT protocols. When compared to the MSCT device, the CBCT devices offer
      a 3D view of the wrist at significantly lower effective doses.

PMID- 29040708
TI  - HPLC Analysis to Determine the Half-life and Bioavailability of the Termiticides
      Bifenthrin and Fipronil in Soil.
AB  - The aim of this study was to test the bioavailability and degradation in soil of
      the termiticides bifenthrin and fipronil, which are used to treat subterranean
      termites (Heterotermes indicola, Wasmann). Soil collected from different areas of
      Lahore was categorized as sandy clay loam (SCL) or sandy loam (SL). Laboratory
      bioassays were conducted to determine the bioavailability ratio of bifenthrin and
      fipronil in each type of soil after different periods of time. LT50 values were
      determined posttreatment at different time intervals. Regarding soil type, both
      termiticides were more effective in SL soil, compared with SCL soil
      posttreatment. There were significant differences in termite mortality in treated
      compared with untreated control samples (P < 0.005). To test the degradation rate
      of soil termiticides, both qualitative and quantitative analyses were carried out
      by HPLC, and the effect of time on termiticide recovery rate determined.
      Calculated half-life values for bifenthrin (maximum, 1,002 and 1,262 d in SCL
      soil and SL soil, respectively) indicated that it persisted in both soil types at
      all concentrations. The maximum calculated half-life values of fipronil were 270
      and 555 d in SCL and SL soil, respectively. At lower concentrations and over
      longer periods of time, fipronil completely degraded in SL soil, while a
      negligible amount was detected in SCL soil. Termiticide concentration decreased
      over time, as did the termiticide recovery rate. Overall, bifenthrin was more
      persistent than fipronil under all treatment conditions tested.

PMID- 29040709
TI  - Occupational asthma caused by an epoxy amine hardener.
AB  - We describe a 43-year-old epoxy floor layer who developed work-related asthma
      while exposed to an epoxy hardener based on isophorone diamine (IPDA). Challenge
      exposures to the curing of the epoxy resin system and subsequently to the
      polyfunctional amine hardener containing IPDA both elicited delayed asthmatic
      reactions. This report further indicates that exposure to epoxy hardeners
      containing polyfunctional amines should be considered as a potential cause of
      occupational asthma. Appropriate work hygiene measures should be implemented to
      minimize airborne exposure to these volatile compounds.

PMID- 29040710
TI  - Quality Improvement Feature Series Article 3: Writing and Reviewing Quality
      Improvement Manuscripts.
AB  - Achieving rapid and meaningful improvement in healthcare requires the
      dissemination of quality improvement project results via publication. Doing this
      well requires detailed descriptions of the complex interventions and of the
      context in which the improvement took place. This report builds on the first 2
      articles in the series to cover important considerations in writing quality
      improvement manuscripts with a focus on how it differs from writing traditional
      clinical research reports. The recommendations we outline here also apply to
      reviewing quality improvement manuscripts.

PMID- 29040711
TI  - Diagnosis and Outcome of Biopsies of Indeterminate Lesions of the Cavernous Sinus
      and Meckel's Cave: A Retrospective Case Series in 85 Patients.
AB  - BACKGROUND: When clinical presentation, laboratory studies, or imaging cannot
      diagnose cavernous sinus (CS) and/or Meckel's cave (MC) lesions, biopsy may be
      necessary. OBJECTIVE: To review our institutional series of biopsies of
      indeterminate CS and MC lesions. METHODS: Records from January 1994 to June 2016
      were searched for biopsied indeterminate CS and MC lesions. We defined
      indeterminate as having an atypical imaging appearance or a broad differential
      and the need for tissue for definitive diagnosis. We defined primary tumors as
      originating from cells inherent or near the CS and MC. RESULTS: Eighty-five
      patients were included (median age 59 [2-85] yr); 22 (28%) had a cancer history.
      Approaches included frontotemporal craniotomy (n = 48, 56%), endoscopic endonasal
      (n = 20, 24%), percutaneous transforamen ovale (n = 12, 14%), or retrosigmoid
      craniotomy (n = 5, 6%). Final diagnosis was metastatic in 27 (32%), primary in 21
      (25%), inflammatory in 13 (15%), hematologic in 11 (13%), fungal in 5 (5%), and
      nondefinitive or nondiagnostic in 8 (10%) patients. Thirteen (59%) patients with
      a cancer history (n = 22) had a diagnosis consistent with their prior cancer; the
      remaining had a second pathology (n = 6, 27%) or nondiagnostic biopsy (n = 3,
      14%). Two patients had surgical complications resulting in death. CONCLUSION: In
      this patient cohort, metastatic tumors were the most likely pathology. The biopsy
      threshold should be lower in patients with a cancer history if clinical or
      radiographic diagnosis is uncertain as 27% had a second disease. However, we
      consider biopsy as a last resort because the risk of major morbidity/mortality,
      while low, is not zero.

PMID- 29040714
TI  - NICE issues positive recommendation for XELJANZ(r)?(tofacitinib citrate) as a new
      treatment option for adults with severe rheumatoid arthritis.

PMID- 29040712
TI  - Signal, Uncertainty, and Conflict in Phylogenomic Data for a Diverse Lineage of
      Microbial Eukaryotes (Diatoms, Bacillariophyta).
AB  - Diatoms (Bacillariophyta) are a species-rich group of eukaryotic microbes diverse
      in morphology, ecology, and metabolism. Previous reconstructions of the diatom
      phylogeny based on one or a few genes have resulted in inconsistent resolution or
      low support for critical nodes. We applied phylogenetic paralog pruning
      techniques to a data set of 94 diatom genomes and transcriptomes to infer
      perennially difficult species relationships, using concatenation and summary
      coalescent methods to reconstruct species trees from data sets spanning a wide
      range of thresholds for taxon and column occupancy in gene alignments. Conflicts
      between gene and species trees decreased with both increasing taxon occupancy and
      bootstrap cutoffs applied to gene trees. Concordance between gene and species
      trees was lowest for short internodes and increased logarithmically with
      increasing edge length, suggesting that incomplete lineage sorting
      disproportionately affects species tree inference at short internodes, which are
      a common feature of the diatom phylogeny. Although species tree topologies were
      largely consistent across many data treatments, concatenation methods appeared to
      outperform summary-coalescent methods for sparse alignments. Our results
      underscore that approaches to species-tree inference based on few loci are likely
      to be misled by unrepresentative sampling of gene histories, particularly in
      lineages that may have diversified rapidly. In addition, phylogenomic studies of
      diatoms, and potentially other hyperdiverse groups, should maximize the number of
      gene trees with high taxon occupancy, though there is clearly a limit to how many
      of these genes will be available.

PMID- 29040715
TI  - The Integrated Pain Team: A Mixed-Methods Evaluation of the Impact of an Embedded
      Interdisciplinary Pain Care Intervention on Primary Care Team Satisfaction,
      Confidence, and Perceptions of Care Effectiveness.
AB  - Objective: To evaluate the impact of the Integrated Pain Team (IPT)-an
      interdisciplinary chronic pain care intervention embedded in primary care at a
      large Veterans Affairs health care system. Outcomes evaluated included IPT's
      impact on the perceived effectiveness of chronic pain care; provider self
      confidence; and primary care team satisfaction, stress, and burnout. Method: This
      mixed-methods quality-improvement study employed: 1) qualitative semistructured
      interviews of 61 primary care providers, other primary care team members, and
      organizational stakeholders; and 2) a supplementary quantitative survey of 65
      providers, comparing those who had referred patients to IPT with those who had
      not. Results: Most interview participants reported that IPT improved chronic pain
      care by providing patients with a comprehensive pain treatment plan, educating
      them about opioid risks, and introducing multimodal treatment options.
      Interviewed care team members reported improved patient education and fewer
      emotionally charged contacts from patients. Interviewed providers felt that IPT
      allowed them to focus their time on health concerns other than pain. However, our
      supplemental survey found that IPT-utilizing providers were no more confident
      than other providers in their own pain care skills or in their relationships with
      chronic pain patients. Conclusions: Integrating an interdisciplinary chronic pain
      care intervention into primary care can provide needed support to care teams and
      may improve chronic pain care. Elements of the IPT model identified as important
      to its effectiveness include its interdisciplinary biopsychosocial approach and
      attentive patient follow-up. However, enhancing providers' confidence and self
      efficacy in chronic pain care may require educational and support resources
      beyond the current IPT model.

PMID- 29040713
TI  - Human Argonaute3 has slicer activity.
AB  - Of the four human Argonaute (AGO) paralogs, only AGO2 has been shown to have
      slicer activity. The others (AGO1, AGO3 and AGO4) have been thought to assemble
      with microRNAs to form slicer-independent effector complexes that bind target
      mRNAs and silence gene expression through translational repression and
      deadenylation but not cleavage. Here, we report that recombinant AGO3 loaded with
      miR-20a cleaves complementary target RNAs, whereas AGO3 loaded with let-7a, miR
      19b or miR-16 does not, indicating that AGO3 has slicer activity but that this
      activity depends on the guide RNA. Our cleavage assays using chimeric guides
      revealed the significance of seed sequence for AGO3 activity, which depends
      specifically on the sequence of the post-seed. Unlike AGO2, target cleavage by
      AGO3 requires both 5'- and 3'-flanking regions. Our 3.28 A crystal structure
      shows that AGO3 forms a complete active site mirroring that of AGO2, but not a
      well-defined nucleic acid-binding channel. These results demonstrating that AGO3
      also has slicer activity but with more intricate substrate requirements, explain
      the observation that AGO3 has retained the necessary catalytic residues
      throughout its evolution. In addition, our structure inspires the idea that the
      substrate-binding channel of AGO3 and consequently its cellular function, may be
      modulated by accessory proteins.

PMID- 29040717
TI  - Letter: Reconsidering Bone Morphogenetic Protein in the Cervical Spine: Selective
      Use for Managing Type II Odontoid Fractures in the Elderly.

PMID- 29040718
TI  - The McConnell's Capsular Arteries and Their Relevance in Endoscopic Endonasal
      Approach to the Sellar Region.
AB  - BACKGROUND: The McConnell's capsular arteries (MCCA) were first described in
      1953. They consist of medial branches of the cavernous internal carotid artery
      (ICA) and are divided in anterior and inferior capsular arteries. OBJECTIVE: To
      highlight the anatomy of the MCCA and its importance in the surgical treatment of
      tuberculum sellae and planum sphenoidale tumors through an endoscopic endonasal
      approach. METHODS: Ten cadaveric specimens fixed in formalin and perfused with
      colored silicone were dissected. Standard endoscopic endonasal transsphenoidal
      approach to the sellar region was performed. The MCCA were identified and still
      images were captured for further analysis. We report 1 case to illustrate the
      importance of the MCCA. RESULTS: The anterior capsular artery, which originates
      from the anteromedial aspect of the anterior loop of the cavernous ICA and
      reaches the suprasellar space, was present in 70% of the specimens with no
      difference between the right and left sides. The anterior capsular artery plays
      an important role in the vascularization of tuberculum sellae meningiomas. The
      inferior capsular artery originates from the inferomedial aspect of the cavernous
      ICA, at its horizontal portion, and reaches the floor and anterior wall of the
      sella where it anastomoses to branches of the inferior hypophyseal artery.
      CONCLUSION: The MCCA are key structures when performing an endoscopic endonasal
      approach for tumors of the sellar and suprasellar regions.

PMID- 29040719
TI  - The Effect of Insecticidal Stress on Reproductive Output of Susceptible and Field
      Strains of Aedes aegypti (Diptera: Culicidae).
AB  - The phenomenon of high egg reproduction when mortality risk rises is common in
      mosquitoes. However, the phenomenon may vary between insecticide susceptible and
      field-collected strains, due to the latter's decreased energy allocation in
      reproduction in the presence of insecticide resistance. In this study, we
      evaluated the effect of chlorpyrifos (CP) and temephos (TP) exposure on the
      oviposition and survival of Aedes aegypti (Linnaeus) (Diptera: Culicidae) using a
      susceptible strain (KHsm) and two field strains (KHly and TNnorth). We also
      dissected the female mosquitoes of each strain on fifth day after the first blood
      meal to examine the total number of eggs produced. Neither CP nor TP exhibited
      oviposition deterrent against female mosquitoes of any of the three strains, as
      the females did not show decreased reproduction activity on the insecticide
      treated sites. Of the two insecticides tested, only CP had an adulticidal effect
      on Ae. aegypti. High mortality was recorded in KHsm after contacting the CP
      treated oviposition sites on day 4. Before death, KHsm mosquitoes oviposited
      significantly more eggs compared to the two field strains. However, the
      difference of total egg production between susceptible and field-collected
      strains was subtle. Thus, the decreased reproductive output in field-collected
      strains might not be directly linked to energy and resource allocation. In this
      respect, we should consider the possible involvement of biogenic amines in the
      egg retention in field-collected strains when mortality risk rises. The
      phenomenon was not observed in nonadulticidal TP treatment.

PMID- 29040720
TI  - Genome-wide prediction of minor-groove electrostatic potential enables
      biophysical modeling of protein-DNA binding.
AB  - Protein-DNA binding is a fundamental component of gene regulatory processes, but
      it is still not completely understood how proteins recognize their target sites
      in the genome. Besides hydrogen bonding in the major groove (base readout),
      proteins recognize minor-groove geometry using positively charged amino acids
      (shape readout). The underlying mechanism of DNA shape readout involves the
      correlation between minor-groove width and electrostatic potential (EP). To probe
      this biophysical effect directly, rather than using minor-groove width as an
      indirect measure for shape readout, we developed a methodology, DNAphi, for
      predicting EP in the minor groove and confirmed the direct role of EP in protein
      DNA binding using massive sequencing data. The DNAphi method uses a sliding
      window approach to mine results from non-linear Poisson-Boltzmann (NLPB)
      calculations on DNA structures derived from all-atom Monte Carlo simulations. We
      validated this approach, which only requires nucleotide sequence as input, based
      on direct comparison with NLPB calculations for available crystal structures.
      Using statistical machine-learning approaches, we showed that adding EP as a
      biophysical feature can improve the predictive power of quantitative binding
      specificity models across 27 transcription factor families. High-throughput
      prediction of EP offers a novel way to integrate biophysical and genomic studies
      of protein-DNA binding.

PMID- 29040722
TI  - Head and Neck: Skull Base Imaging.
AB  - There are a myriad of head and neck pathologies that extend from the extracranial
      to the intracranial compartment, traversing the skull base, and knowledge of the
      imaging appearance of this pathology is critical to practicing neurosurgeons.
      This article reviews some of the important inflammatory or acquired head and neck
      pathology along the skull base, neoplastic skull base lesions, and the
      intracranial extension of head and neck malignancy. Focus will be on the relevant
      anatomy, appropriate imaging protocols to evaluate these processes, as well as
      the differentiating imaging findings on computed tomography and magnetic
      resonance imaging.

PMID- 29040721
TI  - Ratio of Endogenous Secretory Receptor for Advanced Glycation End Products to
      Pentosidine Predicts Fractures in Men.
AB  - Context: Although the endogenous secretory receptor for advanced glycation end
      products (esRAGE) has been associated with reduced activity of pentosidine (PEN),
      the association between PEN, esRAGE, and fracture is poorly understood.
      Objectives: To evaluate the ability of serum PEN and esRAGE levels to predict
      fragility fractures. Methods: A cohort of 1285 Japanese men aged >=65 years old
      participated in a 2007 to 2008 Fujiwara-kyo Osteoporosis Risk in Men study
      baseline survey, as part of the Fujiwara-kyo prospective cohort study. Those
      participants provided information regarding any fractures they experienced during
      5 years. The baseline bone mineral density (BMD) was measured. Hazard ratios
      (HRs) per one standard deviation increase of log-transformed serum levels of PEN,
      esRAGE, and esRAGE-to-PEN ratio were estimated at baseline. Results: Twenty-five
      participating men suffered incident clinical fragility fractures. The crude HRs
      (95% confidence interval) for PEN, esRAGE, and esRAGE-to-PEN ratio were 1.56
      (1.05 to 2.31), 0.79 (0.54 to 1.15), and 0.65 (0.44 to 0.95), respectively. HRs
      for PEN adjusted for age, esRAGE, and T score of BMD at femoral neck (FN) and
      lumbar spine (LS) were 1.48 (1.00 to 2.18) and 1.51 (1.03 to 2.21), respectively.
      The marginal significance adjusted for BMD at FN and the statistical significance
      adjusted for BMD at LS were attenuated after additional adjustment for glycated
      hemoglobin A1c level (P = 0.111 and 0.072, respectively). The HRs for esRAGE-to
      PEN ratio adjusted for age, glycated hemoglobin A1c, and T-score of BMD at FN and
      LS were 0.67 (0.45 to 0.98) and 0.64 (0.43 to 0.95). Conclusions: Higher esRAGE
      to-PEN ratios were associated with decreased risk of fragility fractures
      independent of BMD among elderly Japanese men.

PMID- 29040724
TI  - ADDITIONAL CHARACTERISATION OF THE THERMAL NEUTRON PILE AT THE NATIONAL PHYSICAL
      LABORATORY, UK.
AB  - As part of its wide-ranging neutron metrology capabilities, the National Physical
      Laboratory in the UK has a thermal neutron facility in which accelerator-produced
      neutrons are moderated within a large assembly or pile of graphite bricks. The
      neutron field has previously been well characterised in terms of the fluence rate
      and energy spectrum at various irradiation positions. However, recent changes to
      the structure (e.g. enlarging the central irradiation cavity) have prompted a
      renewal and extension of this work. We have also used Monte Carlo modelling to
      improve our understanding of the pile's performance.

PMID- 29040723
TI  - Resting-state functional connectivity in combat veterans suffering from impulsive
      aggression.
AB  - Impulsive aggression is common among military personnel after deployment and may
      arise because of impaired top-down regulation of the amygdala by prefrontal
      regions. This study sought to further explore this hypothesis via resting-state
      functional connectivity analyses in impulsively aggressive combat veterans. Male
      combat veterans with (n = 28) and without (n = 30) impulsive aggression problems
      underwent resting-state functional magnetic resonance imaging. Functional
      connectivity analyses were conducted with the following seed-regions: basolateral
      amygdala (BLA), centromedial amygdala, anterior cingulate cortex (ACC), and
      anterior insular cortex (AIC). Regions-of-interest analyses focused on the
      orbitofrontal cortex and periaqueductal gray, and yielded no significant results.
      In exploratory cluster analyses, we observed reduced functional connectivity
      between the (bilateral) BLA and left dorsolateral prefrontal cortex in the
      impulsive aggression group, relative to combat controls. This finding indicates
      that combat-related impulsive aggression may be marked by weakened functional
      connectivity between the amygdala and prefrontal regions, already in the absence
      of explicit emotional stimuli. Group differences in functional connectivity were
      also observed between the (bilateral) ACC and left cuneus, which may be related
      to heightened vigilance to potentially threatening visual cues, as well as
      between the left AIC and right temporal pole, possibly related to negative memory
      association in impulsive aggression.

PMID- 29040726
TI  - Interhospital Transfer of Neurosurgical Patients.

PMID- 29040725
TI  - Protein S-Nitrosylation Regulates Xylem Vessel Cell Differentiation in
      Arabidopsis.
AB  - Post-translational modifications of proteins have important roles in the
      regulation of protein activity. One such modification, S-nitrosylation, involves
      the covalent binding of nitric oxide (NO)-related species to a cysteine residue.
      Recent work showed that protein S-nitrosylation has crucial functions in plant
      development and environmental responses. In the present study, we investigated
      the importance of protein S-nitrosylation for xylem vessel cell differentiation
      using a forward genetics approach. We performed ethyl methanesulfonate
      mutagenesis of a transgenic Arabidopsis 35S::VND7-VP16-GR line in which the
      activity of VASCULAR-RELATED NAC-DOMAIN7 (VND7), a key transcription factor
      involved in xylem vessel cell differentiation, can be induced post
      translationally by glucocorticoid treatment, with the goal of obtaining
      suppressor mutants that failed to differentiate ectopic xylem vessel cells; we
      named these mutants suppressor of ectopic vessel cell differentiation induced by
      VND7 (seiv) mutants. We found the seiv1 mutant to be a recessive mutant in which
      ectopic xylem cell differentiation was inhibited, especially in aboveground
      organs. In seiv1 mutants, a single nucleic acid substitution (G to A) leading to
      an amino acid substitution (E36K) was present in the gene encoding S
      NITROSOGLUTATHIONE REDUCTASE 1 (GSNOR1), which regulates the turnover of the
      natural NO donor, S-nitrosoglutathione. An in vitro S-nitrosylation assay
      revealed that VND7 can be S-nitrosylated at Cys264 and Cys320 located near the
      transactivation activity-related domains, which were shown to be important for
      transactivation activity of VND7 by transient reporter assay. Our results suggest
      crucial roles for GSNOR1-regulated protein S-nitrosylation in xylem vessel cell
      differentiation, partly through the post-translational modification of VND7.

PMID- 29040728
TI  - LETTER TO THE EDITOR: COMMENTS ON "ASSESSMENT OF RADIATION DOSE AND EXCESSIVE
      LIFE-TIME CANCER RISK FROM THE BUNAIR GRANITE, NORTHERN PAKISTAN".

PMID- 29040727
TI  - Whole-Genome Sequencing of African Dogs Provides Insights into Adaptations
      against Tropical Parasites.
AB  - Natural selection in domestic dogs is of great interest in evolutionary biology
      since dogs have migrated to every inhabited continent of the world alongside
      humans, and adapted to diverse environments. Here, we explored their demographic
      history and genetic basis of adaptation to the tropical African environment using
      whole genome analyses of 19 African indigenous dogs from Nigeria. Demographic
      analysis suggests that the ancestors of these dogs migrated into Africa from
      Eurasia 14,000 years ago and underwent a severe founder effect before population
      expansion. Admixture analysis further reveals that African dog genomes contain
      about 1.88-3.50% introgression from African golden wolves (Canis anthus).
      Population genetic analysis identifies 50 positively selected genes linked with
      immunity, angiogenesis, ultraviolet protection, as well as insulin secretion and
      sensitivity that may contribute to adaptation to tropical conditions. One of the
      positively selected genes, adhesion G protein-coupled receptor E1 (ADGRE1), has
      also been found to be association with severe malaria resistance in African human
      populations. Functional assessments showed that ADGRE1 provides protective host
      defense against Plasmodium infections. This result, together with the fact that
      the inflammatory response to canine babesiosis is similar to complicated
      falciparum malaria in humans, support the dogs as a model for the study of
      malaria control and treatment.

PMID- 29040730
TI  - Diurnal Temperature Range and Chikungunya Virus Infection in Invasive Mosquito
      Vectors.
AB  - Climate strongly influences the geographic distribution and timing of mosquito
      borne disease outbreaks. Environmental temperature affects phenotypic traits of
      mosquitoes including vector competence for arboviruses mediated by changes in
      infection, extrinsic incubation period and in rates of transmission. Most
      experiments, however, are done at constant temperatures. In nature, mosquitoes
      are more likely to experience daily fluctuations in temperature. Here we compare
      disseminated infection (leg infection) and saliva infection of Aedes aegypti (L.)
      (Diptera: Culicidae) and Aedes albopictus (Skuse) (Diptera: Culicidae) from
      Florida following oral exposure to an Asian genotype of chikungunya virus
      emergent in the Americas. We evaluated experimentally the effect of variable
      temperature regimens on disseminated infection and saliva infection of these
      Aedes species. Each of three temperature regimes had approximately the same
      average temperature (27-28 degrees C), but differed in the magnitude of the
      diurnal temperature range (DTR). The large DTR was 8.0 degrees C (range 23-31
      degrees C) and the small DTR was 4.0 degrees C (range 26-30 degrees C) which
      approximate ranges in different locations of Florida during July-October when
      risk of transmission is highest. The constant temperature was set at 27 degrees
      C. Testing three geographic populations of each mosquito species, significant
      effects on disseminated infection were detected for an interaction between
      temperature regime and geographic population for both Ae. aegypti and Ae.
      albopictus. There were no significant treatment effects of temperature,
      geographic population, or temperature by geographic population interaction on
      saliva infection for either mosquito species. Constant temperature resulted in a
      higher viral load in the saliva of Ae. albopictus, but not Ae. aegypti, compared
      to conditions where the temperature fluctuated.

PMID- 29040731
TI  - Neurocysticercosis versus disseminated intracranial tuberculoma.

PMID- 29040729
TI  - CsrA maximizes expression of the AcrAB multidrug resistance transporter.
AB  - Carbon Storage Regulator A (CsrA) is an RNA binding protein that acts as a global
      regulator of diverse genes. Using a combination of genetics and biochemistry we
      show that CsrA binds directly to the 5' end of the transcript encoding AcrAB.
      Deletion of csrA or mutagenesis of the CsrA binding sites reduced production of
      both AcrA and AcrB. Nucleotide substitutions at the 5' UTR of acrA mRNA that
      could potentially weaken the inhibitory RNA secondary structure, allow for more
      efficient translation of the AcrAB proteins. Given the role of AcrAB-TolC in
      multi-drug efflux we suggest that CsrA is a potential drug target.

PMID- 29040732
TI  - Evidence-Based Pain Medicine: Inconvenient Truths.

PMID- 29040733
TI  - Decreased incidence of gout in diabetic patients using pioglitazone.
AB  - Objective: The incidence and prevalence of gout are increasing, but the
      management is poor. Considering the increased prevalence of gout in the diabetic
      population, this study evaluated the effects of pioglitazone, an insulin
      resistance inhibitor, on the incidence of gout in the diabetic population.
      Methods: We used data from the National Health Insurance program in Taiwan. The
      pioglitazone cohort contained 30 100 patients and each patient was age and sex
      matched with three non-pioglitazone users who were randomly selected from the
      diabetic population. Cox proportional hazards regression analysis was conducted
      to estimate the effects of pioglitazone on the incidence of gout in the diabetic
      population. Results: The incidence of gout was significantly lower in
      pioglitazone users than in non-pioglitazone users [adjusted hazard ratio (aHR)
      0.81 (95% CI 0.78, 0.85)]. The HR for the incidence of gout was lower in both
      male [aHR 0.80 (95% CI 0.75, 0.85)] and female [aHR 0.83 (95% CI 0.78, 0.88)]
      pioglitazone users than in non-pioglitazone users. An analysis of three age
      groups (<40, 40-59 and ?60 years) revealed that the HRs of both the 40-59 years
      [aHR 0.78 (95% CI 0.73, 0.83)] and the ?60 years [aHR 0.85 (95% CI 0.80, 0.91)]
      age groups were significantly lower among pioglitazone users than non
      pioglitazone users. Conclusion: Compared with the non-pioglitazone users, the
      incidence of gout in the diabetic population using pioglitazone was less.

PMID- 29040734
TI  - GEOMETRICAL EFFICIENCY OF PLANE-PARALLEL IONIZATION CHAMBERS IN PROTON SCANNING
      BEAM.
AB  - For commissioning of a proton therapy unit depth dose distributions must be
      determined and introduced into the Treatment Planning System. In pencil beam
      scanning (PBS) technique, integral depth dose (IDD) acquisition should be
      performed with detector large enough to ensure entire beam laterally broadened by
      scattered and secondary contributions. The purpose of this article is to
      quantify, using measurements and Monte Carlo transport calculations, the
      ionization chamber's (IC) geometrical efficiency versus the chamber radius and
      proton beam energy. The geometrical efficiency of 0.99 was determined for
      energies up to 160 and 190 MeV for 4.08 and 6 cm radius IC. Much lower
      geometrical efficiency was obtained for the energy of 226.08 MeV and results in
      charge loss of 5.8 and 3.6%, respectively. Relative IDD differences between IC
      4.08 and 6 cm in radius increase with proton energy and reach 2.4% at the mid
      range depth for 226.08 MeV.

PMID- 29040735
TI  - Kyrle's disease.

PMID- 29040736
TI  - Social media in medicine: a game changer?

PMID- 29040737
TI  - Calcium-driven DNA synthesis by a high-fidelity DNA polymerase.
AB  - Divalent metal ions, usually Mg2+, are required for both DNA synthesis and
      proofreading functions by DNA polymerases (DNA Pol). Although used as a non
      reactive cofactor substitute for binding and crystallographic studies, Ca2+
      supports DNA polymerization by only one DNA Pol, Dpo4. Here, we explore whether
      Ca2+-driven catalysis might apply to high-fidelity (HiFi) family B DNA Pols. The
      consequences of replacing Mg2+ by Ca2+ on base pairing at the polymerase active
      site as well as the editing of terminal nucleotides at the exonuclease active
      site of the archaeal Pyrococcus abyssi DNA Pol (PabPolB) are characterized and
      compared to other (families B, A, Y, X, D) DNA Pols. Based on primer extension
      assays, steady-state kinetics and ion-chased experiments, we demonstrate that
      Ca2+ (and other metal ions) activates DNA synthesis by PabPolB. While showing a
      slower rate of phosphodiester bond formation, nucleotide selectivity is improved
      over that of Mg2+. Further mechanistic studies show that the affinities for
      primer/template are higher in the presence of Ca2+ and reinforced by a correct
      incoming nucleotide. Conversely, no exonuclease degradation of the terminal
      nucleotides occurs with Ca2+. Evolutionary and mechanistic insights among DNA
      Pols are thus discussed.

PMID- 29040739
TI  - Papaya CpEIN3a and CpNAC2 Co-operatively Regulate Carotenoid Biosynthesis-Related
      Genes CpPDS2/4, CpLCY-e and CpCHY-b During Fruit Ripening.
AB  - Papaya is an important tropical fruit with a rich source of carotenoids. The
      ripening of papaya is a physiological and metabolic process with remarkable
      changes including accumulation of carotenoids, which depends primarily on the
      action of ethylene. Ethylene response is mediated by a transcriptional cascade
      involving the transcription factor families of EIN3/EILs and ERFs. Although ERF
      members have been reported to control carotenoid production in Arabidopsis and
      tomato, whether EIN3/EILs are also involved in carotenoid biosynthesis during
      fruit ripening remains unclear. In this work, two EIN3 genes from papaya fruit,
      namely CpEIN3a and CpEIN3b, were studied, of which CpEIN3a was increased during
      fruit ripening, concomitant with the increase of transcripts of carotenoid
      biosynthesis-related genes including CpPDS2/4, CpZDS, CpLCY-e and CpCHY-b, and
      carotenoid content. Electrophoretic mobility shift assays (EMSAs) and transient
      expression analyses revealed that CpEIN3a was able to bind to the promoters of
      CpPDS4 and CpCHY-b, and promoted their transcription. Protein-protein interaction
      assays indicated that CpEIN3a physically interacted with another transcription
      factor CpNAC2, which acted as a transcriptional activator of CpPDS2/4, CpZDS,
      CpLCY-e and CpCHY-b by directly binding to their promoters. More importantly, the
      transcriptional activation abilities of CpPDS2/4, CpLCY-e and CpCHY-b were more
      pronounced following their interaction. Collectively, our findings suggest that
      CpEIN3a interacts with CpNAC2 and, individually or co-operatively, activates the
      transcription of a subset of carotenoid biosynthesis-related genes, providing new
      insights into the regulatory networks of carotenoid biosynthesis during papaya
      fruit ripening.

PMID- 29040738
TI  - NF90-NF45 is a selective RNA chaperone that rearranges viral and cellular
      riboswitches: biochemical analysis of a virus host factor activity.
AB  - The heterodimer NF90-NF45 is an RNA-binding protein complex that modulates the
      expression of various cellular mRNAs on the post-transcriptional level.
      Furthermore, it acts as a host factor that supports the replication of several
      RNA viruses. The molecular mechanisms underlying these activities have yet to be
      elucidated. Recently, we showed that the RNA-binding capabilities and binding
      specificity of NF90 considerably improves when it forms a complex with NF45.
      Here, we demonstrate that NF90 has a substrate-selective RNA chaperone activity
      (RCA) involving RNA annealing and strand displacement activities. The mechanism
      of the NF90-catalyzed RNA annealing was elucidated to comprise a combination of
      'matchmaking' and compensation of repulsive charges, which finally results in the
      population of dsRNA products. Heterodimer formation with NF45 enhances
      'matchmaking' of complementary ssRNAs and substantially increases the efficiency
      of NF90's RCA. During investigations of the relevance of the NF90-NF45 RCA, the
      complex was shown to stimulate the first step in the RNA replication process of
      hepatitis C virus (HCV) in vitro and to stabilize a regulatory element within the
      mRNA of vascular endothelial growth factor (VEGF) by protein-guided changes of
      the RNAs' structures. Thus, our study reveals how the intrinsic properties of an
      RNA-binding protein determine its biological activities.

PMID- 29040740
TI  - Studying Developmental Psychopathology Related to Psychotic Disorders-Challenges
      and Paradigms in Human Studies.

PMID- 29040741
TI  - Identification of new protein-protein and protein-DNA interactions linked with
      wood formation in Populus trichocarpa.
AB  - Cellular processes, such as signal transduction and cell wall deposition, are
      organized by macromolecule interactions. Experimentally determined protein
      protein interactions (PPIs) and protein-DNA interactions (PDIs) relevant to woody
      plant development are sparse. To begin to develop a Populus trichocarpa Torr. &
      A. Gray wood interactome, we applied the yeast-two-hybrid (Y2H) assay in
      different ways to enable the discovery of novel PPIs and connected networks. We
      first cloned open reading frames (ORFs) for 361 genes markedly upregulated in
      secondary xylem compared with secondary phloem and performed a binary Y2H screen
      with these proteins. By screening a xylem cDNA library for interactors of a
      subset of these proteins and then recapitulating the process by using a subset of
      the interactors as baits, we ultimately identified 165 PPIs involving 162
      different ORFs. Thirty-eight transcription factors (TFs) included in our
      collection of P. trichocarpa wood ORFs were used in a Y1H screen for binding to
      promoter regions of three genes involved in lignin biosynthesis resulting in 40
      PDIs involving 20 different TFs. The network incorporating both the PPIs and PDIs
      included 14 connected subnetworks, with the largest having 132 members. Protein
      protein interactions and PDIs validated previous reports and also identified new
      candidate wood formation proteins and modules through their interactions with
      proteins and promoters known to be involved in secondary cell wall synthesis.
      Selected examples are discussed including a PPI between Mps one binder (MOB1) and
      a mitogen-activated protein kinase kinase kinase kinase (M4K) that was further
      characterized by assays confirming the PPI as well as its effect on subcellular
      localization. Mapping of published transcriptomic data showing developmentally
      detailed expression patterns across a secondary stem onto the network supported
      that the PPIs and PDIs are relevant to wood formation, and also illustrated that
      wood-associated interactions involve gene products that are not upregulated in
      secondary xylem.

PMID- 29040742
TI  - Intussusception Rate Among Under-Five-Children Before Introduction of Rotavirus
      Vaccine in North India.
AB  - Background: Baseline data on intussusception are needed to compare the
      intussusception rates following introduction of rotavirus vaccine. Methods: A
      hospital-based bidirectional surveillance (retrospective from 2009 to 2012; and
      prospective from 2013 to 2015) was set up in a tertiary care hospital in
      Chandigarh, India, to enrol children <5 years of age admitted with
      intussusception as per Brighton's classification, to estimate the hospital
      admission rate. Incidence of intussusception among infants and children <5 years
      of age was also estimated. Results: A total of 277 intussusception cases (96
      retrospective; 181 prospective) were reported. Majority of cases were males
      (69.7%) and infants (72%). Median age at diagnosis was 10 months (interquartile
      range 6-12 months). Nearly 62% cases were treated surgically and 33%
      radiologically. Incidence was estimated to be 20/100 000 infants, and 5/100 000
      children <5 years of age per year, in Chandigarh. Conclusion: Intussusception
      surveillance system provided background hospital admission and incidence rate
      before rotavirus vaccine introduction in North India.

PMID- 29040743
TI  - Anger-sensitive networks: characterizing neural systems recruited during
      aggressive social interactions using data-driven analysis.
AB  - Social neuroscience uses increasingly complex paradigms to improve ecological
      validity, as investigating aggressive interactions with functional magnetic
      resonance imaging (fMRI). Standard analyses for fMRI data typically use general
      linear models (GLM), which require a priori models of task effects on neural
      processes. These may inadequately model non-stimulus-locked or temporally
      overlapping cognitive processes, as mentalizing about other agents. We used the
      data-driven approach of independent component analysis (ICA) to investigate
      neural processes involved in a competitive interaction. Participants were
      confronted with an angry-looking opponent while having to anticipate the trial
      outcome and the opponent's behaviour. We show that several spatially distinctive
      neural networks with associated temporal dynamics were modulated by the
      opponent's facial expression. These results dovetail and extend the main effects
      observed in the GLM analysis of the same data. Additionally, the ICA approach
      identified effects of the experimental condition on neural systems during inter
      trial intervals. We demonstrate that cognitive processes during aggressive
      interactions are poorly modelled by simple stimulus onset/duration variables and
      instead have more complex temporal dynamics. This highlights the utility of using
      data-driven analyses to elucidate the distinct cognitive processes recruited
      during complex social paradigms.

PMID- 29040744
TI  - Tobacco exposure and sleep disturbance in 498 208 UK Biobank participants.
AB  - Background: The prevalence of sleep disturbance is high and increasing. The study
      investigated whether active, former and passive smoking were associated with
      sleep disturbance. Methods: This cross-sectional study used data from the UK
      Biobank: a cohort study of 502 655 participants, of whom 498 208 provided self
      reported data on smoking and sleep characteristics. Multivariable multinomial and
      logistic regression models were used to examine the associations between smoking
      and sleep disturbance. Results: Long-sleep duration (>9 h) was more common among
      current smokers [odds ratio (OR): 1.47; 95% confidence interval (CI): 1.17-1.85;
      probability value (P) = 0.001] than never smokers, especially heavy (>20/day)
      smokers (OR: 2.85; 95% CI: 1.66-4.89; P < 0.001). Former heavy (>20/day) smokers
      were also more likely to report short (<6 h) sleep duration (OR: 1.41; 95% CI:
      1.25-1.60; P < 0.001), long-sleep duration (OR: 1.99; 95% CI: 1.47-2.71; P <
      0.001) and sleeplessness (OR: 1.47; 95% CI: 1.38-1.57; P < 0.001) than never
      smokers. Among never smokers, those who lived with more than one smoker had
      higher odds of long-sleep duration than those not cohabitating with a smoker (OR:
      2.71; 95% CI: 1.26-5.82; P = 0.011). Conclusions: Active and passive exposure to
      high levels of tobacco smoke are associated with sleep disturbance. Existing
      global tobacco control interventions need to be enforced.

PMID- 29040745
TI  - The impact of shift work on sleep quality among nurses.
AB  - Background: Shift work is common among nurses, and it is known to be a workplace
      hazard as it may cause poor sleep quality, which can impact adversely on the
      health and safety of nurses and their patients. Aims: To explore factors that
      contribute to poor sleep quality in shift working nurses (SWNs) compared with non
      shift working nurses (NSWNs) and to assess the awareness of support from
      occupational health. Methods: Cross-sectional study of nurses at a National
      Health Service (NHS) foundation trust, February to March 2016. Data were
      collected via an online questionnaire. Sleep quality was measured using the
      Pittsburgh Sleep Quality Index. Results: Eight hundred and eighty-eight nurses
      participated; the response rate was 34%. The prevalence of poor sleep quality was
      78% (95% confidence interval [CI] 0.748-0.813) in the SWNs, compared with 59%
      (95% CI 0.503-0.678) in the NSWNs. There was a mean sleep quality score
      difference of 1.58 between the SWNs and the NSWNs, which was statistically
      significant, P < 0.001 (95% CI 0.913-2.246). Undertaking shift work was the only
      significant association with poor sleep quality when controlling for the other
      variables of age, gender and number of years worked, odds ratio 0.410, P < 0.001
      (95% CI 0.265-0.634). Conclusions: There was a high prevalence of poor sleep
      quality in both SWNs and NSWNs. This was persistent despite few nurses working in
      rotating shifts or shifts with short recovery time.

PMID- 29040746
TI  - CHARACTERIZATION OF AN IN-HOUSE DEVELOPED MULTI-CYLINDRICAL MODERATOR NEUTRON
      SPECTROMETER.
AB  - This article describes the characterization of an in-house developed multi
      cylindrical moderator neutron spectrometer, which consists of a cylindrical 3He
      proportional counter and cylindrical moderator shells of different sizes. The
      response matrix of the spectrometer was calculated by Monte Carlo simulations for
      neutron energies from 1 * 10-8 to 10 MeV and verified with measurements in 0.144
      MeV, 1.2 MeV and 241AmBe neutron standard fields. Influence of scattered neutrons
      was properly eliminated from the measured response using the shadow cone
      technique. The calculated and measured responses were in good agreement in most
      cases. Differences were <10% for all moderated counter configurations, while
      larger deviations were observed for the bare counter configuration. The
      performance of the neutron spectrometer in terms of spectrum unfolding was
      verified in the 241AmBe neutron standard field, showing reliable neutron spectrum
      and fluence rate in the energy range up to 10 MeV as investigated in this work.

PMID- 29040747
TI  - Factors associated with smoking behaviour change in UK military personnel.
AB  - Background: Research in the UK civilian population suggests that poor mental
      health outcomes are associated with smoking behaviour. In the UK military
      population, smoking cessation is associated with deployment in the reserve
      forces. However, little is known about the links between mental health outcomes
      and smoking initiation and cessation in the UK military. Aims: The aim of this
      longitudinal study was to examine change in mental health and military factors
      associated with smoking initiation and cessation in a representative sample of UK
      military personnel. Methods: Data were collected between 2003 and 2009; 5138
      regular and reserve military personnel were included in the analyses. Results:
      The results showed that smoking initiation was associated with symptoms of
      psychological distress, symptoms of probable post-traumatic stress disorder
      (PTSD), relationship breakdown and deployment. Conclusions: These findings are
      consistent with existing research in civilian populations showing links between
      poor mental health and smoking behaviour. Furthermore, our finding that
      deployment is associated with smoking initiation is also in line with research
      from the US military and UK reserves.

PMID- 29040748
TI  - Primary angiitis of the central nervous system-a territory about to be
      discovered.

PMID- 29040749
TI  - Cdc42 regulates the cellular localization of Cdc42ep1 in controlling neural crest
      cell migration.
AB  - The member of Rho family of small GTPases Cdc42 plays important and conserved
      roles in cell polarity and motility. The Cdc42ep family proteins have been
      identified to bind to Cdc42, yet how they interact with Cdc42 to regulate cell
      migration remains to be elucidated. In this study, we focus on Cdc42ep1, which is
      expressed predominantly in the highly migratory neural crest cells in frog
      embryos. Through morpholino-mediated knockdown, we show that Cdc42ep1 is required
      for the migration of cranial neural crest cells. Loss of Cdc42ep1 leads to
      rounder cell shapes and the formation of membrane blebs, consistent with the
      observed disruption in actin organization and focal adhesion alignment. As a
      result, Cdc42ep1 is critical for neural crest cells to apply traction forces at
      the correct place to migrate efficiently. We further show that Cdc42ep1 is
      localized to two areas in neural crest cells: in membrane protrusions together
      with Cdc42 and in perinuclear patches where Cdc42 is absent. Cdc42 directly
      interacts with Cdc42ep1 (through the CRIB domain) and changes in Cdc42 level
      shift the distribution of Cdc42ep1 between these two subcellular locations,
      controlling the formation of membrane protrusions and directionality of migration
      as a consequence. These results suggest that Cdc42ep1 elaborates Cdc42 activity
      in neural crest cells to promote their efficient migration.

PMID- 29040750
TI  - Cool, callous and in control: superior inhibitory control in frequent players of
      video games with violent content.
AB  - Research on the effects of media violence exposure has shown robust associations
      among violent media exposure, increased aggressive behavior, and decreased
      empathy. Preliminary research indicates that frequent players of violent video
      games may have differences in emotional and cognitive processes compared to
      infrequent or nonplayers, yet research examining the amount and content of game
      play and the relation of these factors with affective and cognitive outcomes is
      limited. The present study measured neural correlates of response inhibition in
      the context of implicit attention to emotion, and how these factors are related
      to empathic responding in frequent and infrequent players of video games with
      graphically violent content. Participants completed a self-report measure of
      empathy as well as an affective stop-signal task that measured implicit attention
      to emotion and response inhibition during electroencephalography. Frequent
      players had lower levels of empathy as well as a reduction in brain activity as
      indicated by P100 and N200/P300 event related potentials. Reduced P100 amplitude
      evoked by happy facial expressions was observed in frequent players compared to
      infrequent players, and this effect was moderated by empathy, such that low
      levels of empathy further reduced P100 amplitudes for happy facial expressions
      for frequent players compared to infrequent players. Compared to infrequent
      players, frequent players had reduced N200/P300 amplitude during response
      inhibition, indicating less neural resources were recruited to inhibit behavior.
      Results from the present study illustrate that chronic exposure to violent video
      games modulates empathy and related neural correlates associated with affect and
      cognition.

PMID- 29040751
TI  - EpiDenovo: a platform for linking regulatory de novo mutations to developmental
      epigenetics and diseases.
AB  - De novo mutations (DNMs) have been shown to be a major cause of severe early
      onset genetic disorders such as autism spectrum disorder and intellectual
      disability. Over one million DNMs have been identified in developmental disorders
      by next generation sequencing, but linking these DNMs to the genes that they
      impact remains a challenge, as the majority of them are embedded in non-coding
      regions. As most developmental diseases occur in the early stages of development
      or during childhood, it is crucial to clarify the details of epigenetic
      regulation in early development in order to interpret the mechanisms underlying
      developmental disorders. Here, we develop EpiDenovo, a database that is freely
      available at http://www.epidenovo.biols.ac.cn/, and which provides the
      associations between embryonic epigenomes and DNMs in developmental disorders,
      including several neuropsychiatric disorders and congenital heart disease.
      EpiDenovo provides an easy-to-use web interface allowing users rapidly to find
      the epigenetic signatures of DNMs and the expression patterns of the genes that
      they regulate during embryonic development. In summary, EpiDenovo is a useful
      resource for selecting candidate genes for further functional studies in
      embryonic development, and for investigating regulatory DNMs as well as other
      genetic variants causing or underlying developmental disorders.

PMID- 29040752
TI  - Expansion of the dehydrin gene family in the Pinaceae is associated with
      considerable structural diversity and drought-responsive expression.
AB  - Temperatures are expected to increase over the next century in all terrestrial
      biomes and particularly in boreal forests, where drought-induced mortality has
      been predicted to rise. Genomics research is helping to develop hypotheses
      regarding the molecular basis of drought tolerance and recent work proposed that
      the osmo-protecting dehydrin proteins have undergone a clade-specific expansion
      in the Pinaceae, a major group of conifer trees. The objectives of this study
      were to identify all of the putative members of the gene family, trace their
      evolutionary origin, examine their structural diversity and test for drought
      responsive expression. We identified 41 complete dehydrin coding sequences in
      Picea glauca, which is four times more than most angiosperms studied to date, and
      more than in pines. Phylogenetic reconstructions indicated that the family has
      undergone an expansion in conifers, with parallel evolution implicating the
      sporadic resurgence of certain amino acid sequence motifs, and a major
      duplication giving rise to a clade specific to the Pinaceae. A variety of plant
      dehydrin structures were identified with variable numbers of the A-, E-, S- and K
      segments and an N-terminal (N1) amino acid motif including assemblages specific
      to conifers. The expression of several of the spruce dehydrins was tissue
      preferential under non-stressful conditions or responded to water stress after 7
      18 days without watering, reflecting changes in osmotic potential. We found that
      dehydrins with N1 K2 and N1 AESK2 sequences were the most responsive to the lack
      of water. Together, the family expansion, drought-responsive expression and
      structural diversification involving loss and gain of amino acid motifs suggests
      that subfunctionalization has driven the diversification seen among dehydrin gene
      duplicates. Our findings clearly indicate that dehydrins represent a large family
      of candidate genes for drought tolerance in spruces and in other Pinaceae that
      may underpin adaptability in spatially and temporally variable environments.

PMID- 29040753
TI  - What is the best treatment target in axial spondyloarthritis: tumour necrosis
      factor alpha, interleukin 17, or both?
AB  - After about 15 years of experience with the TNF blockers as the only effective
      drugs in axial spondyloarthritis patients who fail conventional treatment, for
      the first time we see now that another targeted therapy, the inhibition of IL-17,
      is also effective. By indirect comparison of the treatment effect between the two
      types of drugs, efficacy seems to be on a similar level. This raises quite a few
      important questions that are related to both pathogenesis and treatment
      strategies for which the answers are currently largely unknown, but would be of
      great relevance for optimizing therapies. In this article, we discuss these
      questions and ways in which such questions could be answered.

PMID- 29040755
TI  - The Omics Dashboard for interactive exploration of gene-expression data.
AB  - The Omics Dashboard is a software tool for interactive exploration and analysis
      of gene-expression datasets. The Omics Dashboard is organized as a hierarchy of
      cellular systems. At the highest level of the hierarchy the Dashboard contains
      graphical panels depicting systems such as biosynthesis, energy metabolism,
      regulation and central dogma. Each of those panels contains a series of X-Y plots
      depicting expression levels of subsystems of that panel, e.g. subsystems within
      the central dogma panel include transcription, translation and protein maturation
      and folding. The Dashboard presents a visual read-out of the expression status of
      cellular systems to facilitate a rapid top-down user survey of how all cellular
      systems are responding to a given stimulus, and to enable the user to quickly
      view the responses of genes within specific systems of interest. Although the
      Dashboard is complementary to traditional statistical methods for analysis of
      gene-expression data, we show how it can detect changes in gene expression that
      statistical techniques may overlook. We present the capabilities of the Dashboard
      using two case studies: the analysis of lipid production for the marine alga
      Thalassiosira pseudonana, and an investigation of a shift from anaerobic to
      aerobic growth for the bacterium Escherichia coli.

PMID- 29040756
TI  - TCDD, FICZ, and Other High Affinity AhR Ligands Dose-Dependently Determine the
      Fate of CD4+ T Cell Differentiation.
AB  - FICZ and TCDD, two high-affinity AhR ligands, are reported to have opposite
      effects on T cell differentiation with TCDD inducing regulatory T cells and FICZ
      inducing Th17 cells. This dichotomy has been attributed to ligand-intrinsic
      differences in AhR activation, although differences in sensitivity to metabolism
      complicate the issue. TCDD is resistant to AhR-induced metabolism and produces
      sustained AhR activation following a single dose in the MUg/kg range, whereas
      FICZ is rapidly metabolized and AhR activation is transient. Nonetheless, prior
      studies comparing FICZ with TCDD have generally used the same 10-50 MUg/kg dose
      range, and thus the two ligands would not equivalently activate AhR. We
      hypothesized that high-affinity AhR ligands can promote CD4+ T cell
      differentiation into both Th17 cells and Tregs, with fate depending on the extent
      and duration of AhR activation. We compared the immunosuppressive effects of TCDD
      and FICZ, along with two other rapidly metabolized ligands (ITE and 11-Cl-BBQ) in
      an acute alloresponse mouse model. The dose and timing of administration of each
      ligand was optimized for TCDD-equivalent Cyp1a1 induction. When optimized, all of
      the ligands suppressed the alloresponse in conjunction with the induction of
      Foxp3- Tr1 cells on day 2 and the expansion of natural Foxp3+ Tregs on day 10. In
      contrast, a low dose of FICZ induced transient expression of Cyp1a1 and did not
      induce Tregs or suppress the alloresponse but enhanced IL-17 production.
      Interestingly, low doses of the other ligands, including TCDD, also increased IL
      17 production on day 10. These findings support the conclusion that the dose and
      the duration of AhR activation by high-affinity AhR ligands are the primary
      factors driving the fate of T cell differentiation.

PMID- 29040757
TI  - Stomatal oscillations in olive trees: analysis and methodological implications.
AB  - Stomatal oscillations have long been disregarded in the literature despite the
      fact that the phenomenon has been described for a variety of plant species. This
      study aims to characterize the occurrence of oscillations in olive trees (Olea
      europaea L.) under different growing conditions and its methodological
      implications. Three experiments with young potted olives and one with large field
      grown trees were performed. Sap flow measurements were always used to monitor the
      occurrence of oscillations, with additional determinations of trunk diameter
      variations and leaf-level stomatal conductance, photosynthesis and water
      potential also conducted in some cases. Strong oscillations with periods of 30-60
      min were generally observed for young trees, while large field trees rarely
      showed significant oscillations. Severe water stress led to the disappearance of
      oscillations, but moderate water deficits occasionally promoted them.
      Simultaneous oscillations were also found for leaf stomatal conductance, leaf
      photosynthesis and trunk diameter, with the former presenting the highest
      amplitudes. The strong oscillations found in young potted olive trees preclude
      the use of infrequent measurements of stomatal conductance and related variables
      to characterize differences between trees of different cultivars or subjected to
      different experimental treatments. Under these circumstances, our results suggest
      that reliable estimates could be obtained using measurement intervals below 15
      min.

PMID- 29040754
TI  - Development of unique cytotoxic chimeric antigen receptors based on human scFv
      targeting B7H6.
AB  - As a stress-inducible natural killer (NK) cell ligand, B7H6 plays a role in
      innate tumor immunosurveillance and is a fairly tumor selective marker expressed
      on a variety of solid and hematologic cancer cells. Here, we describe the
      isolation and characterization of a new family of single chain fragment variable
      (scFv) molecules targeting the human B7H6 ligand. Through directed evolution of a
      yeast surface displayed non-immune human-derived scFv library, eight candidates
      comprising a single family of clones differing by up to four amino acid mutations
      and exhibiting nM avidities for soluble B7H6-Ig were isolated. A representative
      clone re-formatted as an scFv-CH1-Fc molecule demonstrated specific binding to
      both B7H6-Ig and native membrane-bound B7H6 on tumor cell lines with a binding
      avidity comparable to the previously characterized B7H6-targeting antibody, TZ47.
      Furthermore, these clones recognized an epitope distinct from that of TZ47 and
      the natural NK cell ligand NKp30, and demonstrated specific activity against B7H6
      expressing tumor cells when expressed as a chimeric antigen receptor (CAR) in T
      cells.

PMID- 29040758
TI  - Linking Light Exposure and Subsequent Sleep: A Field Polysomnography Study in
      Humans.
AB  - Study objectives: To determine the effect of light exposure on subsequent sleep
      characteristics under ambulatory field conditions. Methods: Twenty healthy
      participants were fitted with ambulatory polysomnography (PSG) and wrist
      actigraphs to assess light exposure, rest-activity, sleep quality, timing, and
      architecture. Laboratory salivary dim-light melatonin onset was analyzed to
      determine endogenous circadian phase. Results: Later circadian clock phase was
      associated with lower intensity (R2 = 0.34, chi2(1) = 7.19, p < .01), later light
      exposure (quadratic, controlling for daylength, R2 = 0.47, chi2(3) = 32.38, p <
      .0001), and to later sleep timing (R2 = 0.71, chi2(1) = 20.39, p < .0001). Those
      with later first exposure to more than 10 lux of light had more awakenings during
      subsequent sleep (controlled for daylength, R2 = 0.36, chi2(2) = 8.66, p < .05).
      Those with later light exposure subsequently had a shorter latency to first rapid
      eye movement (REM) sleep episode (R2 = 0.21, chi2(1) = 5.77, p < .05). Those with
      less light exposure subsequently had a higher percentage of REM sleep (R2 = 0.43,
      chi2(2) = 13.90, p < .001) in a clock phase modulated manner. Slow-wave sleep
      accumulation was observed to be larger after preceding exposure to high maximal
      intensity and early first light exposure (p < .05). Conclusions: The quality and
      architecture of sleep is associated with preceding light exposure. We propose
      that light exposure timing and intensity do not only modulate circadian-driven
      aspects of sleep but also homeostatic sleep pressure. These novel ambulatory PSG
      findings are the first to highlight the direct relationship between light and
      subsequent sleep, combining knowledge of homeostatic and circadian regulation of
      sleep by light. Upon confirmation by interventional studies, this hypothesis
      could change current understanding of sleep regulation and its relationship to
      prior light exposure. Clinical trial details: This study was not a clinical
      trial. The study was ethically approved and nationally registered
      (NL48468.042.14).

PMID- 29040760
TI  - In Reply: Microsurgical Endoscope-Assisted Gravity-Aided Transfalcine Approach
      for Contralateral Metastatic Deep Medial Cortical Tumors.

PMID- 29040759
TI  - Cervical Alignment Changes in Patients Developing Proximal Junctional Kyphosis
      Following Surgical Correction of Adult Spinal Deformity.
AB  - BACKGROUND: Proximal junctional kyphosis (PJK) following adult spinal deformity
      (ASD) surgery is a well-documented complication, but associations between
      radiographic PJK and cervical malalignment onset remain unexplored. OBJECTIVE: To
      study cervical malalignment in ASD surgical patients that develop PJK. METHODS:
      Retrospective review of prospective multicenter database. Inclusion: primary ASD
      patients (>=5 levels fused, upper instrumented vertebra [UIV] at T2 or above, and
      1-yr minimum follow-up) without baseline cervical deformity (CD), defined as >=2
      of the following criteria: T1 slope minus cervical lordosis < 20 degrees ,
      cervical sagittal vertical axis < 4 cm, C2-C7 cervical lordosis < 10 degrees .
      PJK presence (<10 degrees  change in UIV and UIV + 2 kyphosis) and angle were
      identified 1 yr postoperative. Propensity score matching between PJK and nonPJK
      groups controlled for baseline alignment. Preoperative and 1-yr postoperative
      cervical alignment were compared between PJK and nonPJK patients. RESULTS: One
      hundred sixty-three patients without baseline CD (54.9 yr, 83.9% female) were
      included. PJK developed in 60 (36.8%) patients, with 27 (45%) having UIV above
      T7. PJK patients had significantly greater baseline T1 slope in unmatched and
      propensity score matching comparisons (P < .05). At 1 yr postoperative, PJK
      patients had significantly higher T1 slope (P < .001), C2-T3 Cobb (P = .04), and
      C2-T3 sagittal vertical axis (P = .02). New-onset CD rate in PJK patients was
      15%, and 16.5% in nonPJK patients (P > .05). Increased PJK magnitude was
      associated with increasing T1 slope and C2-T3 SVA (P < .05). CONCLUSION: Patients
      who develop PJK following surgical correction of ASD have a 15% incidence of
      development of new-onset CD. Patients developing PJK following surgical
      correction of ASD tend to have an increased preoperative T1 slope. Increased
      progression of C2-T3 Cobb angle and C2-T3 SVA are associated with development of
      PJK following surgical correction of thoracolumbar deformity.

PMID- 29040761
TI  - PCSD: a plant chromatin state database.
AB  - Genome-wide maps of chromatin states have become a powerful representation of
      genome annotation and regulatory activity. We collected public and in-house plant
      epigenomic data sets and applied a Hidden Markov Model to define chromatin
      states, which included 290 553 (36 chromatin states), 831 235 (38 chromatin
      states) and 3 936 844 (26 chromatin states) segments across the whole genome of
      Arabidopsis thaliana, Oryza sativa and Zea mays, respectively. We constructed a
      Plant Chromatin State Database (PCSD,
      http://systemsbiology.cau.edu.cn/chromstates) to integrate detailed information
      about chromatin states, including the features and distribution of states,
      segments in states and related genes with segments. The self-organization mapping
      (SOM) results for these different chromatin signatures and UCSC Genome Browser
      for visualization were also integrated into the PCSD database. We further
      provided differential SOM maps between two epigenetic marks for chromatin state
      comparison and custom tools for new data analysis. The segments and related genes
      in SOM maps can be searched and used for motif and GO analysis, respectively. In
      addition, multi-species integration can be used to discover conserved features at
      the epigenomic level. In summary, our PCSD database integrated the identified
      chromatin states with epigenetic features and may be beneficial for communities
      to discover causal functions hidden in plant chromatin.

PMID- 29040762
TI  - Effects of Schizophrenia Polygenic Risk Scores on Brain Activity and Performance
      During Working Memory Subprocesses in Healthy Young Adults.
AB  - Recent work has begun to shed light on the neural correlates and possible
      mechanisms of polygenic risk for schizophrenia. Here, we map a schizophrenia
      polygenic risk profile score (PRS) based on genome-wide association study
      significant loci onto variability in the activity and functional connectivity of
      a frontoparietal network supporting the manipulation versus maintenance of
      information during a numerical working memory (WM) task in healthy young adults
      (n = 99, mean age = 19.8). Our analyses revealed that higher PRS was associated
      with hypoactivity of the dorsolateral prefrontal cortex (dlPFC) during the
      manipulation but not maintenance of information in WM (r2 = .0576, P = .018).
      Post hoc analyses revealed that PRS-modulated dlPFC hypoactivity correlated with
      faster reaction times during WM manipulation (r2 = .0967, P = .002), and faster
      processing speed (r2 = .0967, P = .003) on a separate behavioral task. These PRS
      associated patterns recapitulate dlPFC hypoactivity observed in patients with
      schizophrenia during central executive manipulation of information in WM on this
      task.

PMID- 29040765
TI  - Flow Diversion for the Treatment of an Unruptured Paraclinoid Carotid Artery
      Aneurysm.

PMID- 29040763
TI  - Oxytocin effects on self-referential processing: behavioral and neuroimaging
      evidence.
AB  - Oxytocin (OT) influences other-oriented mental processes (e.g. trust and empathy)
      and the underlying neural substrates. However, whether and how OT modulates self
      oriented processes and the underlying brain activity remains unclear. Using a
      double-blind, placebo-controlled between-subjects design, we manipulated memory
      encoding and retrieval of trait adjectives related to the self, a friend and a
      celebrity in a self-referential task in male adults. Experiment 1 (N = 51) found
      that OT vs placebo treatments reduced response times during encoding self-related
      trait adjectives but increased recognition scores of self-related information
      during memory retrieval. Experiment 2 (N = 50) showed similar OT effects on
      response times during encoding self-related trait adjectives. Moreover,
      functional magnetic resonance imaging (fMRI) results revealed that OT vs placebo
      treatments decreased the activity in the medial prefrontal cortex (MPFC) involved
      in encoding of self-related trait adjectives and weakened the coupling between
      the MPFC activity and a cultural trait (i.e. interdependence). Experiment 3 (N =
      52) revealed that OT vs placebo treatments increased the right superior frontal
      activity during memory retrieval of self-related information. The results provide
      behavioral and fMRI evidence for OT effects on self-referential processing and
      suggest distinct patterns of OT modulations of brain activities engaged in
      encoding and retrieval of self-related information.

PMID- 29040764
TI  - Rif1 promotes a repressive chromatin state to safeguard against endogenous
      retrovirus activation.
AB  - Transposable elements, including endogenous retroviruses (ERVs), constitute a
      large fraction of the mammalian genome. They are transcriptionally silenced
      during early development to protect genome integrity and aberrant transcription.
      However, the mechanisms that control their repression are not fully understood.
      To systematically study ERV repression, we carried out an RNAi screen in mouse
      embryonic stem cells (ESCs) and identified a list of novel regulators. Among
      them, Rif1 displays the strongest effect. Rif1 depletion by RNAi or gene deletion
      led to increased transcription and increased chromatin accessibility at ERV
      regions and their neighboring genes. This transcriptional de-repression becomes
      more severe when DNA methylation is lost. On the mechanistic level, Rif1 directly
      occupies ERVs and is required for repressive histone mark H3K9me3 and H3K27me3
      assembly and DNA methylation. It interacts with histone methyltransferases and
      facilitates their recruitment to ERV regions. Importantly, Rif1 represses ERVs in
      human ESCs as well, and the evolutionally-conserved HEAT-like domain is essential
      for its function. Finally, Rif1 acts as a barrier during somatic cell
      reprogramming, and its depletion significantly enhances reprogramming efficiency.
      Together, our study uncovered many previously uncharacterized repressors of ERVs,
      and defined an essential role of Rif1 in the epigenetic defense against ERV
      activation.

PMID- 29040767
TI  - Contribution of the S-type Anion Channel SLAC1 to Stomatal Control and Its
      Dependence on Developmental Stage in Rice.
AB  - Rice production depends on water availability and carbon fixation by
      photosynthesis. Therefore, optimal control of stomata, which regulate leaf
      transpiration and CO2 absorption, is important for high productivity. SLOW ANION
      CHANNEL-ASSOCIATED 1 (SLAC1) is an S-type anion channel protein that controls
      stomatal closure in response to elevated CO2. Rice slac1 mutants showed
      significantly increased stomatal conductance (gs) and enhanced CO2 assimilation.
      To discern the contribution of stomatal regulation to rice growth, we compared gs
      in the wild type (WT) and two mutants, slac1 and the dominant-positive mutant
      SLAC1-F461A, which expresses a point mutation causing an amino acid substitution
      (F461A) in SLAC1, at different growth stages. Because the side group of F461 is
      estimated to function as the channel gate, stomata in the SLAC1-F461A mutant are
      expected to close constitutively. All three lines had maximum gs during the
      tillering stage, when the gs values were 50% higher in slac1 and 70% lower in
      SLAC1-F461A, compared with the WT. At the tillering stage, the gs values were
      highest in the first leaves at the top of the stem and lower in the second and
      third leaves in all three lines. Both slac1 and SLAC1-F461A retained the ability
      to change gs in response to the day-night cycle, and showed differences in
      tillering rate and plant height compared with the WT, and lower grain yield.
      These observations show that SLAC1 plays a crucial role in regulating stomata in
      rice at the tillering stage.

PMID- 29040766
TI  - Brain-to-brain synchronization across two persons predicts mutual prosociality.
AB  - People tend to be more prosocial after synchronizing behaviors with others, yet
      the underlying neural mechanisms are rarely known. In this study, participant
      dyads performed either a coordination task or an independence task, with their
      brain activations recorded via the functional near-infrared spectroscopy
      hyperscanning technique. Participant dyads in the coordination group showed
      higher synchronized behaviors and greater subsequent inclination to help each
      other than those in the independence group, indicating the prosocial effect of
      interpersonal synchrony. Importantly, the coordination group demonstrated the
      significant task-related brain coherence, namely the interbrain synchronization,
      at the left middle frontal area. The detected interbrain synchronization was
      sensitive to shared intentionality between participants and was correlated with
      the mutual prosocial inclination. Further, the task-related brain coherence
      played a mediation role in the prosocial effect of interpersonal synchrony. This
      study reveals the relevance of brain-to-brain synchronization among individuals
      with subsequent mutual prosocial inclination and suggests the neural mechanism
      associating with shared cognition for the facilitation of interpersonal synchrony
      on prosociality.

PMID- 29040768
TI  - OVERVIEW OF NEUTRON MEASUREMENTS IN JET FUSION DEVICE.
AB  - The design and operation of ITER experimental fusion reactor requires the
      development of neutron measurement techniques and numerical tools to derive the
      fusion power and the radiation field in the device and in the surrounding areas.
      Nuclear analyses provide essential input to the conceptual design, optimisation,
      engineering and safety case in ITER and power plant studies. The required
      radiation transport calculations are extremely challenging because of the large
      physical extent of the reactor plant, the complexity of the geometry, and the
      combination of deep penetration and streaming paths. This article reports the
      experimental activities which are carried-out at JET to validate the neutronics
      measurements methods and numerical tools used in ITER and power plant design. A
      new deuterium-tritium campaign is proposed in 2019 at JET: the unique 14 MeV
      neutron yields produced will be exploited as much as possible to validate
      measurement techniques, codes, procedures and data currently used in ITER design
      thus reducing the related uncertainties and the associated risks in the machine
      operation.

PMID- 29040769
TI  - Effect of the Duration of Meteorological Data Collection on the Prospective
      Assessment of Long-Term Atmospheric Dispersion Factors.
AB  - Assessing the environmental dispersion of radioactive effluents from a nuclear
      facility under normal operation is a prerequisite in applying for the
      construction permit and operation license of the facility. In Korea, the Nuclear
      Safety and Security Commission requires at least 1- and 2-year periods of site
      specific meteorological data to assess the atmospheric dispersion of the
      effluents from a nuclear reactor facility for a construction permit and operating
      license, respectively. In this study, we investigated if an extended period of
      meteorological data would be certainly preferable for the prospective assessment
      of dispersion of the atmospheric effluents under current data handling
      approaches. For test estimation, the meteorological data collected in the Kori
      nuclear power plant site in 2001 to 2008 were utilized. We suggest that the
      accumulated meteorological data be reflected in assessing the atmospheric
      dispersion in the form of individual annual data rather than the averaged data
      over the whole period.

PMID- 29040770
TI  - Optimized light-inducible transcription in mammalian cells using Flavin Kelch
      repeat F-box1/GIGANTEA and CRY2/CIB1.
AB  - Light-inducible systems allow spatiotemporal control of a variety of biological
      activities. Here, we report newly optimized optogenetic tools to induce
      transcription with light in mammalian cells, using the Arabidopsis photoreceptor
      Flavin Kelch-repeat F-box 1 (FKF1) and its binding partner GIGANTEA (GI) as well
      as CRY2/CIB1. By combining the mutagenesis of FKF1 with the optimization of a
      split FKF1/GI dimerized Gal4-VP16 transcriptional system, we identified
      constructs enabling significantly improved light-triggered transcriptional
      induction. In addition, we have improved the CRY2/CIB1-based light-inducible
      transcription with split construct optimization. The improvements regarding the
      FKF1/GI- and CRY2/CIB1-based systems will be widely applicable for the light
      dependent control of transcription in mammalian cells.

PMID- 29040772
TI  - Letter: Microsurgical Endoscope-Assisted Gravity-Aided Transfalcine Approach for
      Contralateral Metastatic Deep Medial Cortical Tumors.

PMID- 29040771
TI  - Contrasting ecophysiological strategies related to drought: the case of a mixed
      stand of Scots pine (Pinus sylvestris) and a submediterranean oak (Quercus
      subpyrenaica).
AB  - Submediterranean forests are considered an ecotone between Mediterranean and
      Eurosiberian ecosystems, and are very sensitive to global change. A decline of
      Scots pine (Pinus sylvestris L.) and a related expansion of oak species (Quercus
      spp.) have been reported in the Spanish Pre-Pyrenees. Although this has been
      associated with increasing drought stress, the underlying mechanisms are not
      fully understood, and suitable monitoring protocols are lacking. The aim of this
      study is to bring insight into the physiological mechanisms anticipating
      selective decline of the pines, with particular focus on carbon and water
      relations. For this purpose, we performed a sampling campaign covering two
      growing seasons in a mixed stand of P. sylvestris and Quercus subpyrenaica E.H
      del Villar. We sampled seasonally twig xylem and soil for water isotope
      composition (delta18O and delta2H), leaves for carbon isotope composition
      (delta13C) and stems to quantify non-structural carbohydrates (NSC)
      concentration, and measured water potential and leaf gas exchange. The first
      summer drought was severe for both species, reaching low predawn water potential
      (-2.2 MPa), very low stomatal conductance (12 +/- 1.0 mmol m-2 s-1) and near-zero
      or even negative net photosynthesis, particularly in P. sylvestris (-0.6 +/- 0.34
      MUmol m-2 s-1 in oaks, -1.3 +/- 0.16 MUmol m-2 s-1 in pines). Hence, the tighter
      stomatal control and more isohydric strategy of P. sylvestris resulted in larger
      limitations on carbon assimilation, and this was also reflected in carbon
      storage, showing twofold larger total NSC concentration in oaks than in pines
      (7.8 +/- 2.4% and 4.0 +/- 1.3%, respectively). We observed a faster recovery of
      predawn water potential after summer drought in Q. subpyrenaica than in P.
      sylvestris (-0.8 MPa and -1.1 MPa, respectively). As supported by the isotopic
      data, this was probably associated with a deeper and more reliable water supply
      in Q. subpyrenaica. In line with these short-term observations, we found a more
      pronounced negative effect of steadily increasing drought stress on long-term
      growth in pines compared with oaks. All these observations confer evidence of
      early warning of P. sylvestris decline and indicate the adaptive advantage of Q.
      subpyrenaica in the area.

PMID- 29040773
TI  - Treatment Outcomes of A Randomized Trial of Unruptured Brain Arteriovenous
      Malformation-Eligible Unruptured Brain Arteriovenous Malformation Patients.
AB  - BACKGROUND: The guideline for treating unruptured brain arteriovenous
      malformations (ubAVMs) remains controversial. A Randomized Trial of Unruptured
      Brain Arteriovenous Malformations (ARUBA) reported lower risk of stroke or death
      with conservative management compared to interventional treatment. There were
      numerous limitations to the study, including short follow-up period and
      disproportionate number of patients treated with surgery and embolization.
      OBJECTIVE: To evaluate whether treatment of ARUBA-eligible patients have
      acceptable outcomes at our institution. METHODS: Retrospective analysis was
      performed on 673 patients with brain AVMs treated at our institution between 2001
      and 2014. One hundred five patients were ARUBA eligible and included in the
      study. Patients were divided into the microsurgery or Gamma Knife Radiosurgery
      (GKS; Elekta, Stockholm, Sweden) arm depending on their final treatment. Mean
      follow-up period was 43 mo (range 4-136 mo). Primary outcome was stroke or death.
      RESULTS: A total of 8 (7.6%) patients had a stroke or died. The overall risk of
      stroke or death was 11.4% (5 of 44 patients) for the microsurgery arm and 4.9% (3
      of 61 patients) for the GKS arm. The annual rates of stroke or death were 2.1%,
      4.0%, and 1.2% for the entire patient cohort, microsurgery arm, and GKS arm,
      respectively. AVM obliteration rates at the end of the follow-up period were
      95.5% and 47.5% for the microsurgery and GKS arms, respectively. CONCLUSION: We
      report a lower overall risk of stroke or death in our ARUBA-eligible patients
      following treatment than ARUBA. Our results suggest that microsurgery and GKS may
      be appropriate treatments for patients with ubAVM.

PMID- 29040774
TI  - Assessing the between-background stability of metabolic effects arising from
      lignin-related transgenic modifications, in two Populus hybrids using non
      targeted metabolomics.
AB  - The advances in 'high-throughput' biology have significantly expanded our
      fundamental understanding of complex biological processes inherent to tree growth
      and development. Relative to the significant achievements attained with whole
      genome re-sequencing and transcriptomics efforts, the development and power of
      post-transcriptional tools such as proteomics and metabolomics continue to lag
      behind in tree biology. However, the inclusion of these powerful functional
      genomics platforms should substantially enable systems biology assessments of
      tree development, physiology and response(s) to biotic and abiotic stresses.
      Herein, we employ a non-targeted metabolomics platform to elucidate the metabolic
      plasticity of xylem lignification in distinct hybrid poplar genetic backgrounds,
      as well as in transgenic trees in these backgrounds expressing two common
      constructs: the first construct (C4H::F5H) augments monolignol content
      (syringyl:guaiacyl (S:G) ratio), while the second construct (C3'H-RNAi) reduces
      cell wall lignification. The results clearly show that genotype-specific
      metabolism exists, and provide an appropriate foundation for properly comparing
      the influence of background on the relationships between metabolic and specific
      phenotypic traits. Moreover, it was apparent that transgene-induced phenotypic
      gradients in cell wall chemical wood can be associated with global metabolism of
      secondary xylem biosynthesis, however in a genotype-specific manner. This result
      implies that the same may be true for phenotypic gradients arising through
      natural genetic variation, intensive breeding or environmental factors. It is
      also apparent that while distinct, at a global level the wood-forming metabolisms
      of different poplar hybrids can, to some extent, respond similarly to the
      influences of genetic manipulation of lignin-related genes. This further implies
      that with the correct approach, it may be possible to associate the emergence of
      specific wood traits from different genetic backgrounds-be they transgene-induced
      or otherwise-with stable metabolic signatures.

PMID- 29040775
TI  - CONSTRUCTION AND TEST OF A PORTABLE TISSUE-EQUIVALENT PROPORTIONAL COUNTER
      SYSTEM.
AB  - Tissue-equivalent proportional counter (TEPC) is a very promising dosemeter for
      radiation protection in mixed radiation fields. In this article, a portable TEPC
      system including a spherical homemade TEPC detector and the compact low-power
      integrated circuit prototype was constructed and tested in gamma and neutron
      radiation fields. The microdosimetric spectra results displayed that the portable
      TEPC system could deal with four orders of magnitude voltage pulse signals. And
      the measured dose equivalent values agreed with reference values, which means the
      portable TEPC system had fulfilled the test and satisfied the requirement for
      radiation monitor.

PMID- 29040777
TI  - Efficient Imaging: Examining the Value of Ultrasound in the Diagnosis of
      Traumatic Adult Brachial Plexus Injuries, A Systematic Review.
AB  - BACKGROUND: Traumatic brachial plexus injury (BPI) can result in debilitating
      sequelae of the upper extremity. Presently, therapeutic decisions are based on
      the mechanism of injury, serial physical examination, electromyography, nerve
      conduction, and imaging studies. While magnetic resonance imaging is the current
      imaging modality of choice for BPI, ultrasound is a promising newcomer that is
      inexpensive, accessible, and available at point of care. OBJECTIVE: To evaluate
      ultrasound as a diagnostic tool in the assessment of traumatic adult BPI through
      a systematic review. METHODS: An electronic literature search was completed in
      MEDLINE, EMBASE, CINAHL, and Cochrane databases up to July 2016. Two independent
      reviewers completed the screening and data extraction. Methodological quality of
      studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies
      2 tool. Statistical analysis was used to estimate pooled sensitivities and study
      heterogeneity. RESULTS: Seven studies were included. Four studies compared the
      detection of pre- and postganglionic lesions at different levels (C5-T1) to
      surgical exploration as the reference standard. Sensitivity of lesion detection
      was greater in the upper and middle spinal nerves: C5 (93%, confidence interval
      [CI] = 78%-100%), C6 (94%, CI = 82%-100%), and C7 (95%, CI = 86%-100%) than in
      the lower: C8 (71%, CI = 36%-95%) and T1 (56%, CI = 29%-81%). CONCLUSION:
      Individual studies demonstrate ultrasound as an effective diagnostic tool for
      traumatic adult BPI. Sensitivity of lesion detection was noted to be greater in
      the upper and middle (C5-C7) than in the lower spinal nerves (C8, T1). Further
      standardized studies should be performed to confirm the utility of ultrasound in
      the diagnosis of traumatic adult BPI.

PMID- 29040776
TI  - Self-reported Cognitive Biases Moderate the Associations Between Social Stress
      and Paranoid Ideation in a Virtual Reality Experimental Study.
AB  - Introduction: Cognitive biases are associated with psychosis liability and
      paranoid ideation. This study investigated the moderating relationship between
      pre-existing self-reported cognitive biases and the occurrence of paranoid
      ideation in response to different levels of social stress in a virtual reality
      environment. Methods: This study included 170 participants with different levels
      of psychosis liability (55 recent onset psychosis, 20 ultrahigh risk for
      psychosis, 42 siblings of psychotic patients, and 53 controls). All participants
      were exposed to virtual environments with different levels of social stress. The
      level of experienced paranoia in the virtual environments was measured with the
      State Social Paranoia Scale. Cognitive biases were assessed with a self-report
      continuous measure. Also, cumulative number of cognitive biases was calculated
      using dichotomous measures of the separate biases, based on general population
      norm scores. Results: Higher belief inflexibility bias (Z = 2.83, P < .001),
      attention to threat bias (Z = 3.40, P < .001), external attribution bias (Z =
      2.60, P < .001), and data-gathering bias (Z = 2.07, P < .05) were all positively
      associated with reported paranoid ideation in the social virtual environments.
      Level of paranoid response increased with number of cognitive biases present (B =
      1.73, P < .001). The effect of environmental stressors on paranoid ideation was
      moderated by attention to threat bias (Z = 2.78, P < .01) and external
      attribution bias (Z = 2.75, P < .01), whereas data-gathering bias and belief
      inflexibility did not moderate the relationship. Conclusion: There is an additive
      effect of separate cognitive biases on paranoid response to social stress. The
      effect of social environmental stressors on paranoid ideation is further enhanced
      by attention to threat bias and external attribution bias.

PMID- 29040778
TI  - Multimodality Management of Recurrent Skull Base Chordomas: Factors Impacting
      Tumor Control and Disease-Specific Survival.
AB  - BACKGROUND: Limited data exist to guide the management of recurrent chordomas
      arising in the skull base. OBJECTIVE: To determine factors affecting tumor
      control rates and disease-specific survival (DSS) in recurrent disease. METHODS:
      A retrospective review was performed of 29 patients with 55 recurrences treated
      at our institution. Tumor and treatment factors were assessed for impact on
      freedom from progression (FFP; primary outcome) and DSS (secondary outcome).
      RESULTS: Postradiotherapy disease failure was much more difficult to manage vs
      progression after surgery alone (15.9 vs 41.4 mo, P = .094). Distant metastases
      and, specifically, leptomeningeal disease at presentation were associated with
      poorer DSS and FFP (P < .05). For local progression after surgery alone, repeat
      resection (P < .05) improved median FFP. With postradiotherapy local failure,
      repeat resection did not confer any benefit (13.5 vs 17.6 mo, P > .05), while a
      trend towards improved FFP was seen with stereotactic radiosurgery (28.3 vs 16.2
      mo, P = .233). For distant metastases, site-directed therapy (surgery or
      radiation) allowed for site control (P < .05) but did not affect FFP or DSS.
      Presentation with early progression <6 mo from previous treatment portended
      significantly worse DSS (19.3 vs 77.6 mo, P < .05). CONCLUSION: There is a need
      for treatment of recurrent disease to be tailored to the pattern of tumor
      recurrence and previously received treatments. Postradiotherapy progression poses
      particular challenges given the apparent limited role of repeat resection alone.
      Stereotactic radiosurgery may have a role in this setting. While patients with
      systemic metastases appear to respond well to site-directed therapy, those with
      leptomeningeal disease have a dismal prognosis.

PMID- 29040779
TI  - The Survival Advantage of "Supratotal".

PMID- 29040781
TI  - Further insights into the components of resistance to Ophiostoma novo-ulmi in
      Ulmus minor: hydraulic conductance, stomatal sensitivity and bark dehydration.
AB  - Dutch elm disease (DED) is a vascular disease that has killed over 1 billion elm
      trees. The pathogen spreads throughout the xylem network triggering vessel
      blockage, which results in water stress, tissue dehydration and extensive leaf
      wilting in susceptible genotypes. We investigated the differences between four
      Ulmus minor Mill. clones of contrasting susceptibility to Ophiostoma novo-ulmi
      Brasier regarding morphological, anatomical and physiological traits affecting
      water transport, in order to gain a better understanding of the mechanisms
      underlying DED susceptibility. We analyzed the differential response to water
      shortage and increased air vapor pressure deficit (VPD) to investigate whether
      resistance to water stress might be related to DED tolerance. Sixteen plants per
      clone, aged 2 years, were grown inside a greenhouse under differential watering.
      Stomatal conductance was measured under ambient and increased VPD. Growth, bark
      water content and stem hydraulic and anatomical parameters were measured 22 days
      after starting differential watering. Vessel lumen area, lumen fraction and
      hydraulic conductance were highest in susceptible clones. Stomatal conductance
      was lowest under low VPD and decreased faster under increased VPD in resistant
      clones. We found a negative relationship between the decrease in stomatal
      conductance at increased VPD and specific hydraulic conductance, revealing a
      narrower hydraulic margin for sustaining transpiration in resistant clones. The
      effect of water shortage was greater on radial stem growth than on leaf area,
      which could be explained through an extensive use of capacitance water to buffer
      xylem water potential. Water shortage reduced stomatal conductance and vessel
      lumen area. Bark water content under conditions of water shortage only decreased
      in susceptible clones. Higher hydraulic constraints to sap flow in resistant
      clones may determine higher stomatal sensitivity to VPD and so contribute to DED
      resistance by limiting pathogen expansion and reducing water loss and metabolic
      impairment in cells involved in fighting against infection.

PMID- 29040780
TI  - Fear boosts the early neural coding of faces.
AB  - The rapid extraction of facial identity and emotional expressions is critical for
      adapted social interactions. These biologically relevant abilities have been
      associated with early neural responses on the face sensitive N170 component.
      However, whether all facial expressions uniformly modulate the N170, and whether
      this effect occurs only when emotion categorization is task-relevant, is still
      unclear. To clarify this issue, we recorded high-resolution electrophysiological
      signals while 22 observers perceived the six basic expressions plus neutral. We
      used a repetition suppression paradigm, with an adaptor followed by a target face
      displaying the same identity and expression (trials of interest). We also
      included catch trials to which participants had to react, by varying identity
      (identity-task), expression (expression-task) or both (dual-task) on the target
      face. We extracted single-trial Repetition Suppression (stRS) responses using a
      data-driven spatiotemporal approach with a robust hierarchical linear model to
      isolate adaptation effects on the trials of interest. Regardless of the task,
      fear was the only expression modulating the N170, eliciting the strongest stRS
      responses. This observation was corroborated by distinct behavioral performance
      during the catch trials for this facial expression. Altogether, our data
      reinforce the view that fear elicits distinct neural processes in the brain,
      enhancing attention and facilitating the early coding of faces.

PMID- 29040782
TI  - EGFR heterogeneity and implications for therapeutic intervention in glioblastoma.
AB  - Patients with glioblastoma (GBM) have a universally poor prognosis and are in
      urgent need of effective treatment strategies. Recent advances in sequencing
      techniques unraveled the complete genomic landscape of GBMs and revealed profound
      heterogeneity of individual tumors even at the single cell level. Genomic
      profiling has detected epidermal growth factor receptor (EGFR) gene alterations
      in more than half of GBMs. Major genetic events include amplification and
      mutation of EGFR. Yet, treatment strategies targeting EGFR have thus far failed
      in clinical trials. In this review, we discuss the clonal and functional
      heterogeneity of EGFRs in GBM development and critically reassess the potential
      of EGFRs as therapeutic targets.

PMID- 29040783
TI  - PATIENT EXPOSURE FROM NUCLEAR MEDICINE IN FRANCE: NATIONAL FOLLOW-UP AND
      INFLUENCE OF THE TECHNOLOGY THROUGH DIAGNOSTIC REFERENCE LEVELS DATA ANALYSIS.
AB  - The Nuclear Safety and Radiation Protection French Institute (IRSN) presents its
      latest assessment from up-to-date diagnostic reference levels (DRL) national data
      in nuclear medicine (NM). NM departments annually send data to IRSN to estimate
      the representativeness of current DRLs. Complementary analyses of the data have
      been performed to evaluate the influence of equipment evolution on practice and
      patient radiation exposure. Based on data from almost 90% of the French NM
      departments, some DRL update are proposed. The analysis of positron emission
      tomography data show that the more the time of flight technology is available on
      equipment, the lower is the administered activity to the patient. IRSN recommends
      updating DRL regulation with current and relevant examination data. The influence
      of technology evolution appeared to be positive for patient exposure and the
      results showed an obvious involvement of professionals in the radiation dose
      optimisation process.

PMID- 29040784
TI  - Tuberculous pneumonia.

PMID- 29040785
TI  - Engineering a temperature sensitive tobacco etch virus protease.
AB  - Since tobacco etch virus protease (TEVp) has a high specificity and efficiency in
      cleaving its target substrates, many groups have attempted to engineer
      conditional control of its activity. Temperature induction is widely used for
      modulating gene function because it has fast temporal response, good
      penetrability and applicability to many model organisms. Here, we engineered a
      temperature sensitive TEVp (tsTEVp) by using N-terminal truncations to TEVp that
      achieved efficient proteolysis on a timescale of 4 h after 30 degrees C
      induction, while remaining relatively inactive at 37 degrees C. As demonstration,
      tsTEVp was used to generate temperature-induced biological responses for protein
      translocation, protein degradation and Ca2+-mediated cellular blebbing. Lastly,
      tsTEVp and their engineered target substrates could find applications in
      engineered synthetic biological systems.

PMID- 29040786
TI  - DEVELOPMENT, CHARACTERIZATION AND TESTING OF A SIMPLIFIED BONNER SPHERE SYSTEM
      FOR RAPID NEUTRON FIELD CHARACTERIZATION.
AB  - Personal neutron dosimetry requires workplace specific correction factors from
      detailed neutron field characterization. A Bonner sphere system (BSS) with a 3He
      proportional counter and a 3 inch an a 9 inch sphere was developed at SCK.CEN for
      rapid neutron field characterization. The BSS energy and angular responses were
      simulated with MCNPX and validated by irradiations with a thermal neutron beam at
      the Belgian Reactor 1 (BR1) and 252Cf and Am-Be sources at the SCK.CEN Laboratory
      for Nuclear Calibration (LNK). The BSS unfolding performance was tested using the
      FRUIT unfolding code for measurements of the scattered neutron field at the LNK.
      The unfolded spectra were in good agreement with MCNPX simulations.

PMID- 29040787
TI  - Why size matters: the interactive influences of tree diameter distribution and
      sap flow parameters on upscaled transpiration.
AB  - In stands with a broad range of diameters, a small number of very large trees can
      disproportionately influence stand basal area and transpiration (Et). Sap flow
      based Et estimates may be particularly sensitive to large trees due to nonlinear
      relationships between tree-level water use (Q) and tree diameter at breast height
      (DBH). Because Q is typically predicted on the basis of DBH and sap flow rates
      measured in a subset of trees and then summed to obtain Et, we assessed the
      relative importance of DBH and sap flow variables (sap velocity, Vs, and sapwood
      depth, Rs) in determining the magnitude of Et and its dependence on large trees
      in a tropical montane forest ecosystem. Specifically, we developed a data-driven
      simulation framework to vary the relationship between DBH and Vs and stand DBH
      distribution and then calculate Q, Et and the proportion of Et contributed by the
      largest tree in each stand. Our results demonstrate that variation in how Rs is
      determined in the largest trees can alter estimates up to 26% of Et while
      variation in how Vs is determined can vary results by up to 132%. Taken together,
      these results highlight a great need to expand our understanding of water
      transport in large trees as this hinders our ability to predict water fluxes
      accurately from stand to catchment scales.

PMID- 29040789
TI  - A REVIEW OF NATURAL RADIONUCLIDES IN CANADIAN DRINKING WATER (1975-16).
AB  - Historical results of natural radioactivity in drinking water were reviewed for a
      total of 21 communities across Canada from 1975 to 2016. Analyses for 226Ra,
      210Pb and total uranium were carried out on monthly composite samples of drinking
      water from selected Canadian municipalities. Generally speaking, levels of 226Ra,
      210Pb and total uranium were found to be low compared to national and
      international standards for drinking water quality. Because levels were low,
      federal monitoring programs were discontinued in most communities in 1986 except
      for Regina, Elliot Lake and Port Hope. The population-weighted average levels for
      these three communities, using data from the most recent 5 years, are <1 mBq/L
      for 226Ra, <5 mBq/L for 210Pb and <0.4 MUg/L for total uranium. The average
      effective dose resulting from drinking water intake at these levels would be <4.3
      MUSv per year.

PMID- 29040790
TI  - Goodbye Paper: We are Moving to Online Only Publication.

PMID- 29040788
TI  - Familial Mediterranean fever mutations are hypermorphic mutations that
      specifically decrease the activation threshold of the Pyrin inflammasome.
AB  - Objectives: FMF is the most frequent autoinflammatory disease and is associated
      in most patients with bi-allelic MEFV mutations. MEFV encodes Pyrin, an
      inflammasome sensor activated following RhoGTPase inhibition. The functional
      consequences of MEFV mutations on the ability of Pyrin variants to act as
      inflammasome sensors are largely unknown. The aim of this study was to assess
      whether MEFV mutations affect the ability of Pyrin to detect RhoGTPase inhibition
      and other inflammasome stimuli. Methods: IL-1beta and IL-18 released by monocytes
      from healthy donors (HDs) and FMF patients were measured upon specific engagement
      of the Pyrin, NLRP3 and NLRC4 inflammasomes. Cell death kinetics following Pyrin
      activation was monitored in real time. Results: Monocytes from FMF patients
      secreted significantly more IL-1beta and IL-18 and died significantly faster than
      HD monocytes in response to low concentrations of Clostridium difficile toxin B
      (TcdB), a Pyrin-activating stimulus. Monocytes from patients bearing two MEFV
      exon 10 pathogenic variants displayed an increased Pyrin inflammasome response
      compared with monocytes from patients with a single exon 10 pathogenic variant
      indicating a gene-dosage effect. Using a short priming step, the response of
      monocytes from FMF patients to NLRP3- and NLRC4-activating stimuli was normal
      indicating that MEFV mutations trigger a specific hypersensitivity of monocytes
      to low doses of a Pyrin-engaging stimulus. Conclusion: Contrary to the NLRP3
      mutations described in cryopyrin-associated periodic syndrome, FMF-associated
      MEFV mutations do not lead to a constitutive activation of Pyrin. Rather, FMF
      associated mutations are hypermorphic mutations that specifically decrease the
      activation threshold of the Pyrin inflammasome without affecting other canonical
      inflammasomes.

PMID- 29040791
TI  - From the Cover: Roles of mmu_piR_003399 in Microcystin-Leucine Arginine-Induced
      Reproductive Toxicity in the Spermatogonial Cells and Testis.
AB  - Our previous work has demonstrated that microcystin-leucine arginine (MC-LR) is a
      potent toxin for the reproductive system of male mice and it exerts cytotoxicity
      in spermatogonial cells, resulting in the constitutional and functional changes
      of the mouse testis. The present study was designed to investigate the functions
      of P-element-induced wimpy (piwi)-interacting RNAs (piRNAs) in MC-LR-induced
      reproductive toxicity in male mice. We observed an increase in the mmu_piR_003399
      level in spermatogonial cells and mouse testicular tissues following treatment
      with MC-LR. Moreover, our data confirmed that cyclin-dependent kinase 6 (CDK6)
      was the target gene of mmu_piR_003399. Increases in the concentration of
      mmu_piR_003399 were correlated with the reduced expression of CDK6 both in vitro
      and in vivo. mmu_piR_003399 induced cell cycle arrest at the G1-phase, down
      regulated sperm counts and sperm motility, and compromised sperm morphology. On
      the contrary, suppressing the expression of mmu_piR_003399 could substantially
      attenuate MC-LR-induced pathology in mice including cell cycle arrest, reduced
      mature sperm counts, sperm viability loss and abnormal sperm morphology.
      Furthermore, our data supported that mmu_piR_003399 existed in mouse serum and
      plasma, and its level was increased in MC-LR-treated mice. In conclusion, we
      demonstrate that mmu_piR_003399 plays a crucial role in regulating MC-LR-induced
      reproductive toxicity.

PMID- 29040792
TI  - Future of Days Past: Neurodevelopment and Schizophrenia.
AB  - Since a proposal in 1986 that schizophrenia involved early neurodevelopmental
      deviations beginning in intrauterine life that showed varying expressivity as
      relevant neural systems matured, our understanding of the developmental
      components of the pathogenesis of schizophrenia has substantially evolved. This
      commentary highlights recent genetic and epigenetic evidence that prenatal
      development is a critical period for the expression of schizophrenia risk.
      Studies of gene expression have been fairly consistent in showing that genes
      implicated in schizophrenia show relatively greater expression during fetal than
      postnatal life. Consistent molecular evidence of early environmental
      perturbations contributing to risk has emerged from studies of epigenetic marks
      in the brain genome as potential environmental footprints and these also
      highlight the prenatal period. Analyses of gene expression in placenta
      dramatically identify the intrauterine environment as a direct point of impact of
      a component of schizophrenia genetic risk. Together, the enrichment of
      transcriptional and epigenetic associations with schizophrenia during fetal life
      suggest that both genetic and environmental risk for schizophrenia have a
      particular molecular impact on early development, possibly because of genetic
      biases in environmental sensitivity.

PMID- 29040793
TI  - Two MATE Transporters with Different Subcellular Localization are Involved in Al
      Tolerance in Buckwheat.
AB  - Buckwheat (Fagopyrum esculentum) shows high tolerance to aluminum (Al) toxicity,
      but the molecular mechanisms responsible for this high Al tolerance are still
      poorly understood. Here, we investigated the involvement of two MATE (multi-drug
      and toxic compound extrusion) genes in Al tolerance. Both FeMATE1 and FeMATE2
      showed efflux transport activity for citrate, but not for oxalate when expressed
      in Xenopus oocytes. A transient assay with buckwheat leaf protoplasts using green
      fluorescent protein (GFP) fusion showed that FeMATE1 was mainly localized to the
      plasma membrane, whereas FeMATE2 was localized to the trans-Golgi and Golgi. The
      expression of FeMATE1 was induced by Al only in the roots, but that of FeMATE2
      was up-regulated in both the roots and leaves. Furthermore, the expression of
      both genes only responded to Al toxicity, but not to other stresses including low
      pH, cadmium (Cd) and lanthanum (La). Heterologous expression of FeMATE1 or
      FeMATE2 in the Arabidopsis mutant atmate partially rescued its Al tolerance.
      Expression of FeMATE1 also partially recovered the Al-induced secretion of
      citrate in the transgenic lines, whereas expression of FeMATE2 did not complement
      the citrate secretion. Further physiological analysis showed that buckwheat roots
      also secreted citrate in addition to oxalate in response to Al in a dose
      responsive manner. Taken together, our results indicate that FeMATE1 is involved
      in the Al-activated citrate secretion in the roots, while FeMATE2 is probably
      responsible for transporting citrate into the Golgi system for the internal
      detoxification of Al in the roots and leaves of buckwheat.

PMID- 29040794
TI  - Evaluating the peptide structure prediction capabilities of a purely ab-initio
      method.
AB  - DEEPSAM is a relatively new global optimization algorithm aimed to predict the
      structure of bio-molecules from sequence, without any additional preliminary
      assumption. It is an evolutionary algorithm whose mutation operators are built by
      hybridizing the diffusion equation method, molecular dynamics simulated
      annealing, and a quasi-Newton local minimization method. The goal of this study
      was to evaluate the structure prediction capabilities of DEEPSAM by running it
      upon NMR structures of linear peptides (10-20 residues). The results indicate
      that DEEPSAM successfully predicted the conformations of these peptides, using
      modest computing resources.

PMID- 29040795
TI  - Case Presentation of Anti-NMDA Receptor Encephalitis in a 4-Year-Old Boy.
AB  - We report a case of a 4-year-old boy from Oyo, Nigeria, presenting with prolonged
      seizures and coma with the subsequent development of oro-lingual-facial
      dyskinesia with frequent tongue thrusting, dysconjugate gaze and choreoathetoid
      movements of the limbs because of autoimmune encephalitis consistent with anti-N
      methyl-D-aspartate (anti-NMDAR) encephalitis.

PMID- 29040796
TI  - An anterior-posterior axis within the ventromedial prefrontal cortex separates
      self and reward.
AB  - Although theoretical discourse and experimental studies on the self- and reward
      biases have a long tradition, currently we have only a limited understanding of
      how the biases are represented in the brain and, more importantly, how they
      relate to each other. We used multi-voxel pattern analysis to test for common
      representations of self and reward in perceptual matching in healthy human
      subjects. Voxels across an anterior-posterior axis in ventromedial prefrontal
      cortex (vmPFC) distinguished (i) self-others and (ii) high-low reward, but cross
      generalization between these dimensions decreased from anterior to posterior
      vmPFC. The vmPFC is characterized by a shift from a common currency for value to
      independent, distributed representations of self and reward across an anterior
      posterior axis. This shift reflected changes in functional connectivity between
      the posterior part of the vmPFC and the frontal pole when processing self
      associated stimuli, and the middle frontal gyrus when processing stimuli
      associated with high reward. The changes in functional connectivity were
      correlated with behavioral biases, respectively, to the self and reward. The
      distinct representations of self and reward in the posterior vmPFC are associated
      with self- and reward-biases in behavior.

PMID- 29040797
TI  - Attention Deficit Hyperactivity Disorder Symptoms and Psychosis in 22q11.2
      Deletion Syndrome.
AB  - OBJECTIVE: 22q11.2 Deletion Syndrome (22q11.2DS) is associated with increased
      risk for schizophrenia in adulthood while Attention Deficit Hyperactivity
      Disorder (ADHD) is the most prevalent diagnosis in childhood. Inattention
      symptoms are pronounced in 22q11.2DS and given that attentional impairment is a
      core feature of schizophrenia, inattention symptoms may reflect underlying ADHD,
      psychosis, or both. We investigate whether inattention is associated with
      psychosis in 22q11.2DS and in other groups at risk for psychosis but without the
      deletion (ND) (idiopathic clinical risk and first degree family members of
      individuals with schizophrenia). METHODS: One hundred thirty-seven individuals
      with 22q11.2DS (mean age: 14.0), 84 ND individuals with subthreshold psychosis
      (mean age: 16.9) and 31 ND individuals with family history of psychosis (mean
      age: 17.0) were included in the study. Psychopathology was assessed using
      research diagnostic assessments. RESULTS: ADHD total symptoms were associated
      with overall levels of subthreshold psychosis symptoms in 22q11.2DS (beta = .8, P
      = .04). Inattention symptoms were specifically associated with positive (beta =
      .5, P = .004), negative (beta = .5, P = .03), and disorganized (beta = .5, P <
      .001) symptoms, while hyperactivity-impulsivity symptoms were associated with
      disorganized symptoms (beta = .5, P = .01). The prevalence of ADHD inattention
      symptoms was higher in 22q11.2DS with subthreshold psychosis compared to ND
      individuals with subthreshold psychosis (P < .001), even when adjusting for
      cognitive impairment and overall psychopathology. The pattern was similar when
      comparing individuals with 22q11.2DS and ND individuals with family history of
      psychosis. CONCLUSIONS: This is the first study to examine the associations
      between ADHD symptoms and psychosis in 22q11.2DS. Our findings support a
      potentially important role of ADHD inattention symptoms in psychosis in
      22q11.2DS.

PMID- 29040799
TI  - Winter survival of Scots pine seedlings under different snow conditions.
AB  - Future climate scenarios predict increased air temperatures and precipitation,
      particularly at high latitudes, and especially so during winter. Soil
      temperatures, however, are more difficult to predict, since they depend strongly
      on the fate of the insulating snow cover. 'Rain-on-snow' events and warm spells
      during winter can lead to thaw-freeze cycles, compacted snow and ice encasement,
      as well as local flooding. These adverse conditions could counteract the
      otherwise positive effects of climatic changes on forest seedling growth. In
      order to study the effects of different winter and snow conditions on young Scots
      pine (Pinus sylvestris L.) seedlings, we conducted a laboratory experiment in
      which 80 1-year-old Scots pine seedlings were distributed between four winter
      treatments in dasotrons: ambient snow cover (SNOW), compressed snow and ice
      encasement (ICE), flooded and frozen soil (FLOOD) and no snow (NO SNOW). During
      the winter treatment period and a 1.5-month simulated spring/early summer phase,
      we monitored the needle, stem and root biomass of the seedlings, and determined
      their starch and soluble sugar concentrations. In addition, we assessed the
      stress experienced by the seedlings by measuring chlorophyll fluorescence,
      electric impedance and photosynthesis of the previous-year needles. Compared with
      the SNOW treatment, carbohydrate concentrations were lower in the FLOOD and NO
      SNOW treatments where the seedlings had almost died before the end of the
      experiment, presumably due to frost desiccation of aboveground parts during the
      winter treatments. The seedlings of the ICE treatment showed dead needles and
      stems only above the snow and ice cover. The results emphasize the importance of
      an insulating and protecting snow cover for small forest tree seedlings, and that
      future winters with changed snow patterns might affect the survival of tree
      seedlings and thus forest productivity.

PMID- 29040798
TI  - Assessment of Cognition and Personality as Potential Endophenotypes in the
      Western Australian Family Study of Schizophrenia.
AB  - Phenotypic heterogeneity is a major barrier to understanding the genetic
      architecture underlying schizophrenia. Incorporating endophenotypes is one way to
      reduce heterogeneity and facilitate more powerful genetic analysis. Candidate
      endophenotypes require systematic assessment against endophenotype criteria, and
      a ranking of their potential utility for genetic analysis. In this study we
      assess 20 cognitive and personality measures in a sample of 127 families with at
      least 2 cases of schizophrenia per family (n = 535) plus a set of 30 control
      families (n = 121) against 4 endophenotype criteria: (a) be associated with the
      illness but not be a part of its diagnosis, (b) be heritable, (c) co-segregate
      with the illness in families, and (d) be found in unaffected relatives at a
      higher rate than in the general population. The endophenotype ranking score
      (endophenotype ranking variable [ERV]) was used to rank candidate endophenotypes
      based on their heritability and genetic correlation with schizophrenia. Finally,
      we used factor analysis to explore latent factors underlying the cognitive and
      personality measures. Evidence for personality measures as endophenotypes was at
      least equivalent to that of the cognitive measures. Factor analysis indicated
      that personality and cognitive traits contribute to independent latent
      dimensions. The results suggest for this first time that a number of cognitive
      and personality measures are independent and informative endophenotypes. Use of
      these endophenotypes in genetic studies will likely improve power and facilitate
      novel aetiological insights.

PMID- 29040801
TI  - Molecular-Level Insight into the Interaction of Phospholipid Bilayers with
      Cellulose.
AB  - Molecular-level insight into the interactions of phospholipid molecules with
      cellulose is crucial for the development of novel cellulose-based materials for
      wound dressing. Here we employ the state-of-the-art computer simulations to
      unlock for the first time the molecular mechanisms behind such interactions. To
      this end, we performed a series of atomic-scale molecular dynamics simulations of
      phospholipid bilayers on a crystalline cellulose support at various hydration
      levels of the bilayer leaflets next to the cellulose surface. Our findings
      clearly demonstrate the existence of strong interactions between polar lipid head
      groups and the hydrophilic surface of a cellulose crystal. We identified two
      major types of interactions between phospholipid molecules and cellulose chains:
      (i) direct attractive interactions between lipid choline groups and oxygens of
      hydroxyl (hydroxymethyl) groups of cellulose and (ii) hydrogen bonding between
      phosphate groups of lipids and cellulose's hydroxymethyl/hydroxyl groups. When
      the hydration level of the interfacial bilayer/support region is low, these
      interactions lead to a pronounced asymmetry in the properties of the opposite
      bilayer leaflets. In particular, the mass density profiles of the proximal
      leaflets are split into two peaks and lipid head groups become more horizontally
      oriented with respect to the bilayer surface. Furthermore, the lateral mobility
      of lipids in the leaflets next to the cellulose surface is found to slow down
      considerably. Most of these cellulose-induced effects are likely due to hydrogen
      bonding between lipid phosphate groups and hydroxymethyl/hydroxyl groups of
      cellulose: the lipid phosphate groups are pulled toward the water/lipid interface
      due to the formation of hydrogen bonds. Overall, our findings shed light on the
      molecular details of the interactions between phospholipid bilayers and cellulose
      nanocrystals and can be used for identifying possible strategies for improving
      the properties of cellulose-based dressing materials via, e.g., chemical
      modification of their surface.

PMID- 29040800
TI  - Ocriplasmin for symptomatic vitreomacular adhesion.
AB  - BACKGROUND: Symptomatic vitreomacular adhesion (sVMA) is a recognised cause of
      visual loss and by tradition has been managed by pars plana vitrectomy (PPV). A
      less invasive alternative to surgery in some people is enzymatic vitreolysis,
      using an intravitreal injection of ocriplasmin. OBJECTIVES: To assess the
      efficacy and safety of ocriplasmin compared to no treatment, sham or placebo for
      the treatment of sVMA. SEARCH METHODS: We searched the Cochrane Central Register
      of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision
      Trials Register) (2017, Issue 1), MEDLINE Ovid (1946 to 24 February 2017), Embase
      Ovid (1947 to 24 February 2017), PubMed (1946 to 24 February 2017), the ISRCTN
      registry (www.isrctn.com/editAdvancedSearch); searched 24 February 2017,
      ClinicalTrials.gov (www.clinicaltrials.gov); searched 24 February 2017 and the
      World Health Organization (WHO) International Clinical Trials Registry Platform
      (ICTRP) (www.who.int/ictrp/search/en); searched 24 February 2017. We did not use
      any date or language restrictions in the electronic searches for trials.
      SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people
      with sVMA. The intervention was intravitreal ocriplasmin 125 MUg injection, and
      this was compared to placebo or sham injection (control). Placebo was defined as
      a single intravitreal injection of 0.10 mL placebo with identical drug vehicle
      diluted with saline. A sham injection was defined as the syringe hub or blunt
      needle touching the conjunctiva to simulate an injection. DATA COLLECTION AND
      ANALYSIS: Two authors independently selected relevant trials, assessed
      methodological quality and extracted data. We graded the certainty of the
      evidence using the GRADE approach. MAIN RESULTS: This review included four RCTs
      conducted in Europe and the USA with a total of 932 eyes of 932 participants.
      Participants were 18 to 97 years of age, with evidence of focal vitreomacular
      adhesion (VMA) on optical coherence tomography (OCT) imaging, with a best
      corrected visual acuity (BCVA) of 20/25 or worse in the study eye and 20/400 or
      better in the fellow eye. The interventions compared were intravitreal
      ocriplasmin versus sham (two RCTs) or placebo (two RCTs) injection. Both sham and
      placebo injection were classified as the control group. The main outcome measures
      were assessed at 28 days and six months. Overall, we judged the studies to have a
      low or unclear risk of bias. All four RCTs were sponsored by the manufacturers of
      ocriplasmin.Compared with control, ocriplasmin treatment was more likely to
      result in VMA release within 28 days (risk ratio (RR) 3.46, 95% confidence
      interval (CI) 2.00 to 6.00; 859 eyes, 4 RCTs, high-certainty evidence).
      Approximately 97/1000 eyes will have VMA release within 28 days without
      treatment. An additional 237 eyes will have VMA release within 28 days for every
      1000 eyes treated with ocriplasmin (95% CI 96 more to 482 more).Treatment with
      ocriplasmin was also more likely to result in macular hole closure (RR 2.87, 95%
      CI 1.50 to 5.51; 229 eyes, 3 RCTs, high-certainty evidence). Approximately
      123/1000 eyes with macular holes will have closure with no treatment. An
      additional 231 eyes will have macular hole closure for every 1000 eyes treated
      with ocriplasmin (95% CI 62 more to 556 more).Eyes receiving ocriplasmin were
      also more likely to have complete posterior vitreous detachment (PVD) within 28
      days (RR 2.94, 95% CI 1.39 to 6.24; 689 eyes, 3 RCTs, high-certainty evidence).
      Approximately 40/1000 eyes will have complete PVD within 28 days without
      treatment. An additional 78 eyes will have complete PVD within 28 days for every
      1000 eyes treated with ocriplasmin (95% CI 16 more to 210 more).Eyes receiving
      ocriplasmin were more likely to achieve 3-line or greater improvement in BCVA at
      six months (RR 1.95, 95% CI 1.07 to 3.53; 674 eyes, 3 RCTs, moderate-certainty
      evidence). Approximately 61/1000 eyes will have a 3-line or greater improvement
      in BCVA at six months without treatment. An additional 58 eyes will have 3-line
      or greater improvement in BCVA at six months for every 1000 eyes treated with
      ocriplasmin (95% CI 9 more to 154 more).Receiving ocriplasmin also reduced the
      requirement for vitrectomy at six months (RR 0.67, 95% CI 0.50 to 0.91; 689 eyes,
      3 RCTs, moderate-certainty evidence). Approximately 265/1000 eyes will require
      vitrectomy at six months without treatment and 87 fewer eyes will require
      vitrectomy for every 1000 eyes treated with ocriplasmin (95% CI 24 fewer to 132
      fewer).Treatment with ocriplasmin resulted in a greater improvement in validated
      Visual Function Questionnaire form score at six months (mean improvement
      difference 2.7 points, 95% CI 0.8 to 4.6; 652 eyes, 2 RCTs, moderate-certainty
      evidence).Eyes receiving ocriplasmin were more likely to have an adverse event
      (RR 1.22, 95% CI 1.09 to 1.37, 909 eyes, 4 RCTs, moderate-certainty evidence).
      Approximately 571/1000 eyes will have an adverse event with sham or placebo
      injection and 106 more eyes will have an adverse event for every 1000 eyes
      treated with ocriplasmin (95% CI 52 more to 212 more). AUTHORS' CONCLUSIONS:
      Evidence from a limited number of RCTs suggests that ocriplasmin is useful in the
      treatment of sVMA. However, up to 20% of eyes treated with ocriplasmin will still
      require additional treatment with PPV within six months. There were more ocular
      adverse events in eyes treated with ocriplasmin than control (sham or placebo
      injection) treatment. Many of these adverse events, particularly vitreous
      floaters and photopsia, are known to be associated with posterior vitreous
      detachment. At present however, there is minimal published long-term safety data
      on eyes treated with ocriplasmin. Further large RCTs comparing ocriplasmin with
      other management options for sVMA would be beneficial.

PMID- 29040802
TI  - Freezing Temperatures, Ice Nanotubes Structures, and Proton Ordering of TIP4P/ICE
      Water inside Single Wall Carbon Nanotubes.
AB  - A very recent experimental paper importantly and unexpectedly showed that water
      in carbon nanotubes is already in the solid ordered phase at the temperature
      where bulk water boils. The water models used so far in literature for molecular
      dynamics simulations in carbon nanotubes show freezing temperatures lower than
      the experiments. We present here results from molecular dynamics simulations of
      water inside single walled carbon nanotubes using an extremely realistic model
      for both liquid and icy water, the TIP4P/ICE. The water behavior inside nanotubes
      of different diameters has been studied upon cooling along the isobars at ambient
      pressure starting from temperatures where water is in a liquid state. We studied
      the liquid/solid transition, and we observed freezing temperatures higher than in
      bulk water and that depend on the diameter of the nanotube. The maximum freezing
      temperature found is 390 K, which is in remarkable agreement with the recent
      experimental measurements. We have also analyzed the ice structure called "ice
      nanotube" that water forms inside the single walled carbon nanotubes when it
      freezes. The ice forms observed are in agreement with previous results obtained
      with different water models. A novel finding, a partial proton ordering, is
      evidenced in our ice nanotubes at finite temperature.

PMID- 29040803
TI  - Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymer and Their
      Nanomicelles for Nonviral Gene Delivery Applications.
AB  - The aim of this study was to synthesize and characterize fatty acid-grafted
      chitosan (fatty acid-g-CS) polymer and their nanomicelles for use as carriers for
      gene delivery. CS was hydrophobically modified using saturated fatty acids of
      increasing fatty acyl chain length. Carbodiimide along with N-hydroxysuccinimide
      was used for coupling carboxyl group of fatty acids with amine groups of CS.
      Proton nuclear magnetic resonance and Fourier transform infrared spectroscopy
      were used to quantify fatty acyl substitution onto CS backbone. The molecular
      weight distribution of the synthesized polymers was determined using size
      exclusion high performance liquid chromatography and was found to be in range of
      the parent CS polymer (~50 kDa). The critical micelle concentration (cmc) of the
      polymers was determined using pyrene as a fluorescent probe. The cmc was found to
      decrease with an increase in fatty acyl chain length. The amphiphilic fatty acid
      g-CS polymers self-assembled in an aqueous environment to form nanomicelles of
      ~200 nm particle size and slightly positive net charge due to the cationic nature
      of free primary amino groups on CS molecule. These polymeric nanomicelles
      exhibited excellent hemo- and cytocompatibility, as evaluated by in vitro
      hemolysis and MTT cell viability assay, respectively, and showed superior
      transfection efficiency compared to unmodified chitosan and naked DNA. The
      surface of these nanomicelles can be further modified with ligands allowing for
      selective targeting, enhanced cell binding, and internalization. These
      nanomicelles can thus be exploited as potential nonviral gene delivery vectors
      for safe and efficient gene therapy.

PMID- 29040804
TI  - Mechanochemical Synthesis of Carbon Nanothread Single Crystals.
AB  - Synthesis of well-ordered reduced dimensional carbon solids with extended bonding
      remains a challenge. For example, few single-crystal organic monomers react under
      topochemical control to produce single-crystal extended solids. We report a
      mechanochemical synthesis in which slow compression at room temperature under
      uniaxial stress can convert polycrystalline or single-crystal benzene monomer
      into single-crystalline packings of carbon nanothreads, a one-dimensional sp3
      carbon nanomaterial. The long-range order over hundreds of microns of these
      crystals allows them to readily exfoliate into fibers. The mechanochemical
      reaction produces macroscopic single crystals despite large dimensional changes
      caused by the formation of multiple strong, covalent C-C bonds to each monomer
      and a lack of reactant single-crystal order. Therefore, it appears not to follow
      a topochemical pathway, but rather one guided by uniaxial stress, to which the
      nanothreads consistently align. Slow-compression room-temperature synthesis may
      allow diverse molecular monomers to form single-crystalline packings of polymers,
      threads, and higher dimensional carbon networks.

PMID- 29040805
TI  - Electrochemical Capacitance of CO-Terminated Pt(111) Dominated by the CO-Solvent
      Gap.
AB  - The distribution of electric fields within the electrochemical double layer
      depends on both the electrode and electrolyte in complex ways. These fields
      strongly influence chemical dynamics in the electrode-electrolyte interface but
      cannot be measured directly with submolecular resolution. We report experimental
      capacitance measurements for aqueous interfaces of CO-terminated Pt(111). By
      comparing these measurements with first-principles density functional theory
      (DFT) calculations, we infer microscopic field distributions and decompose
      contributions to the inverse capacitance from various spatial regions of the
      interface. We find that the CO is strongly electronically coupled to the Pt and
      that most of the interfacial potential difference appears across the gap between
      the terminating O and water and not across the CO molecule, as previously
      hypothesized. This "gap capacitance" resulting from hydrophobic termination
      lowers the overall capacitance of the aqueous Pt-CO interface and makes it less
      sensitive to electrolyte concentration compared to the bare metal.

PMID- 29040806
TI  - Bacterial Derived Carbohydrates Bind Cyr1 and Trigger Hyphal Growth in Candida
      albicans.
AB  - The dimorphic yeast Candida albicans is the most common pathogenic fungus found
      in humans. While this species is normally commensal, a morphological switch from
      budding yeast to filamentous hyphae allows the fungi to invade epithelial cells
      and cause infections. The phenotypic change is controlled by the adenylyl
      cyclase, Cyr1. Interestingly, this protein contains a leucine-rich repeat (LRR)
      domain, which is commonly found in innate immune receptors from plants and
      animals. A functional and pure LRR domain was obtained in high yields from E.
      coli expression. Utilizing a surface plasmon resonance assay, the LRR was found
      to bind diverse bacterial derived carbohydrates with high affinity. This domain
      is capable of binding fragments of peptidoglycan, a carbohydrate polymer
      component of the bacterial cell wall, as well as anthracyclines produced by
      Streptomyces, leading to hyphae formation. These findings add another dimension
      to the human microbiome, taking into account yeast-bacteria interactions that
      occur in the host.

PMID- 29040807
TI  - Photochemical Control over Oscillations in Chemical Reaction Networks.
AB  - Systems chemistry aims to emulate the functional behavior observed in living
      systems by constructing chemical reaction networks (CRNs) with well-defined
      dynamic properties. Future expansion of the complexity of these systems would
      require external control to tune behavior and temporal organization of such CRNs.
      In this work, we design and implement a photolabile probe, which upon irradiation
      strengthens the negative feedback loop of a CRN that produces oscillations of
      trypsin under out-of-equilibrium conditions. By changing the timing and duration
      of irradiation, we can tailor the temporal response of the network.

PMID- 29040808
TI  - Independently Tuning the Biochemical and Mechanical Properties of 3D Hyaluronan
      Based Hydrogels with Oxime and Diels-Alder Chemistry to Culture Breast Cancer
      Spheroids.
AB  - For native breast cancer cell growth to be mimicked in vitro as spheroids, a well
      defined matrix that mimics the tumor microenvironment is required. Finding a
      biomimetic material for 3D cell culture other than Matrigel has challenged the
      field. Because hyaluronan is naturally abundant in the tumor microenvironment and
      can be chemically modified, we synthesized a hyaluronan (HA) hydrogel with
      independently tunable mechanical and chemical properties for 3D culture of breast
      cancer cells. By modifying HA with distinct bioorthogonal functional groups, its
      mechanical properties are controlled by chemical cross-linking via oxime
      ligation, and its biochemical properties are controlled by grafting bioactive
      peptides via Diels-Alder chemistry. A series of hydrogels were screened in terms
      of stiffness and peptide composition for cancer spheroid formation. In the
      optimal hydrogel formulation, the 3D breast cancer spheroids showed decreased
      drug diffusion into their core and upregulation of cellular multidrug-resistant
      efflux pumps similar to what is observed in drug-resistant tumors. Our results
      highlight the potential of these tunable and well-defined gels in drug screening
      assays.

PMID- 29040809
TI  - Membrane Permeability of Fatty Acyl Compounds Studied via Molecular Simulation.
AB  - Interest in fatty acid-derived products as fuel and chemical precursors has grown
      substantially. Microbes can be genetically engineered to produce fatty acid
      derived products that are able to cross host membranes and can be extracted into
      an applied organic overlay. This process is thought to be passive, with a rate
      dependent on the chemistry of the crossing compound. The relationship between the
      chemical composition and the energetics and kinetics of product accumulation
      within the overlay is not well understood. Through biased and unbiased molecular
      simulation, we compute the membrane permeability coefficients from production to
      extraction for different fatty acyl products, including fatty acids, fatty
      alcohols, fatty aldehydes, alkanes, and alkenes. These simulations identify
      specific interactions that accelerate the transit of aldehydes across the
      membrane bilayer relative to other oxidized products, specifically the lack of
      hydrogen bonds to the surrounding membrane environment. However, since extraction
      from the outer membrane leaflet into the organic phase is found to be rate
      limiting for the entire process, we find that fatty alcohols and fatty aldehydes
      would both manifest similar fluxes into a dodecane overlay under equivalent
      conditions, outpacing the accumulation of acids or alkanes into the organic
      phase. Since aldehydes are known to be highly reactive as well as toxic in high
      quantities, the findings suggest that indeed fatty alcohols are the optimal long
      tail fatty acyl product for extraction.

PMID- 29040810
TI  - Photothermal Nanoparticle Initiation Enables Radical Polymerization and Yields
      Unique, Uniform Microfibers with Broad Spectrum Light.
AB  - Photothermal processes are utilized across a variety of fields, from separations
      to medicine, and are an area of active research. Herein, the action of a solar
      simulator upon carbon black nanoparticles is shown to result in photothermally
      initiated chain-growth polymerization of methyl acrylate, butyl acrylate, and
      methyl methacrylate initiated by benzoyl peroxide. With use of methyl acrylate as
      the model system, products from this reaction are shown to be apparently
      indistinguishable on the molecular level, but result in unique microstructures
      relative to the thermal controls. The relative contribution of bands of the
      UV/visible spectrum to the polymerization initiation show that red/infrared
      wavelengths are most important for the initiation to occur. Kinetic analysis of
      the initiator homolysis indicate that the apparent reaction rate is accelerated
      in the photothermal condition.

PMID- 29040811
TI  - Mobile emergency simulation training for rural health providers.
AB  - INTRODUCTION: Mobile emergency simulation offers innovative continuing medical
      educational support to regions that may lack access to such opportunities.
      Furthermore, satisfaction is a critical element for active learning. Together,
      the authors evaluated Canadian rural healthcare providers' satisfaction from high
      fidelity emergency simulation training using a modified motorhome as a mobile
      education unit (MEU). METHODS: Over a 5-month period, data was collected during
      14 educational sessions in nine different southern Manitoban communities. Groups
      of up to five rural healthcare providers managed emergency simulation cases
      including polytrauma, severe sepsis, and inferior myocardial infarction with
      right ventricular involvement, followed by a debrief. Participants anonymously
      completed a feedback form that contained 11 questions on a five-point Likert
      scale and six short-answer questions. RESULTS: Data from 131 respondents were
      analyzed, for a response rate of 75.6%. Respondents included nurses (27.5%),
      medical residents (26.7%), medical first responders (16.0%), and physicians
      (12.2%). The median response was 5 for overall quality of learning, development
      of clinical reasoning skills and decision-making ability, recognition of patient
      deterioration, and self-reflection. The post-simulation debrief median response
      was also 5 for summarizing important issues, constructive criticism, and feedback
      to learn. Respondents also reported that the MEU provided a believable working
      environment (87.0%, <i>n</i>=114), they had limited or no previous access to high
      fidelity mannequins (82.7%, <i>n</i>=107), and they had no specific training in
      crisis resource management or were unfamiliar with the term (92%, <i>n</i>=118).
      CONCLUSIONS: A high level of satisfaction was reported in rural health providers
      with mobile emergency simulation. Access to and experience with high fidelity
      mannequins was limited, suggesting areas for potential educational growth.

PMID- 29040812
TI  - A randomized, controlled, crossover study of appetite-related sensations after
      consuming snacks made from buckwheat.
AB  - With the rising incidence of overweight and obesity in developed countries, there
      is an interest in developing food products that may aid in satiety and reduce
      energy intake. Buckwheat (Fagopyrum esculentum) is a gluten-free edible seed that
      has been previously shown to induce changes in postprandial concentrations of
      satiety hormones; however, subjective measures of appetite-related sensations and
      objective measures of energy intake at subsequent meals following buckwheat
      consumption have not been measured. Thirty-eight healthy adults were recruited to
      participate in a randomized, controlled, crossover trial with the main objective
      to determine if consuming snacks made from buckwheat would increase satiety and
      reduce energy intake compared with snacks comparable in serving size, physical
      characteristics, and nutrient composition. Water was included as a no-kilocalorie
      control. Participants received each of the treatments once separated by at least
      7 days. Appetite related sensations were assessed using visual analog scales at
      fasting and after consuming the snack at 30-min intervals for 180 min. Lunch was
      provided at the clinic and the amount of food consumed was weighed. Participants
      recorded food intake for the rest of the day. Consuming buckwheat groats (32 g
      serving; 141 kcal) or pita bread made from buckwheat flour (50 g serving; 135
      kcal) was not associated with changes in appetite related sensations or energy
      consumption compared with reference snack products made from corn or rice flour.
      Sensory questionnaires revealed that snacks made from buckwheat were liked to a
      similar degree or more as reference snack products, which shows commercial
      promise for developing buckwheat-containing snacks.

PMID- 29040813
TI  - Developmental neurotoxic effects of a low dose of TCE on a 3-D neurosphere
      system.
AB  - Trichloroethylene (TCE) is one of the industrial toxic byproducts that now
      persist in the air, soil, and water. Several studies have already illustrated the
      toxic effect of high doses of TCE on the biological functions of several organs.
      This study aims to highlight the toxic impact of a low dose of TCE (1 MUmol/L) on
      the development of rat neural stem cells (NSCs). The subventricular zones (SVZ)
      of rat pup's brains were collected and minced, and the harvested cells were
      cultured in the presence of neural growth factors B27/N2 to develop neurospheres.
      The cells were then exposed to a dose of 1 MUmol/L TCE for 1 or 2 weeks. The
      outcomes indicated a remarkable inhibitory effect of TCE on the differentiation
      capacity of NSCs, which was confirmed by down-regulation of the astrocyte marker
      GFAP The inhibitory effect of TCE on the proliferation of NSCs was identified by
      the reductions in neurosphere diameter, Ki67 expression, and cell cycle arrest at
      the G1/S phase. Immunolabelling with annexin V indicated the proapoptotic effect
      of TCE exposure. PCR results revealed a TCE-mediated suppression of the
      expression of the antioxidant enzyme SOD1. This paper illustrates, for the first
      time, a detailed examination of the toxic effects of an environmentally low dose
      of TCE on NCSs at the transcriptional, translational, and functional levels.

PMID- 29040814
TI  - Inhibiting polo-like kinase 1 enhances radiosensitization via modulating DNA
      repair proteins in non-small-cell lung cancer.
AB  - To assure faithful chromosome segregation, cells make use of the spindle assembly
      checkpoint, which can be activated in aneuploid cancer cells. In this study, the
      efficacies of inhibiting polo-like kinase 1 (PLK1) on the radiosensitization of
      non-small-cell lung cancer (NSCLC) cells were studied. Clonogenic survival assay
      was performed to identify the effects of the PLK1 inhibitor on radiosensitivity
      within NSCLC cells. Mitotic catastrophe assessment was used to measure the cell
      death and histone H2AX protein (gammaH2AX) foci were utilized to assess the DNA
      double-strand breaks (DSB). The transcriptome was analyzed via unbiased profiling
      of microarray expression. The results showed that the postradiation mitotic
      catastrophe induction and the DSB repair were induced by PLK1 inhibitor BI-6727,
      leading to an increase in the radiosensitivity of NSCLC cells. BI-6727 in
      combination with radiation significantly induced the delayed tumor growth. PLK1
      silenced NSCLC cells showed an altered mRNA and protein expression related to DNA
      damaging, replication, and repairing, including the DNA-dependent protein kinase
      (DNAPK) and topoisomerase II alpha (TOPO2A). Furthermore, inhibition of PLK1
      blocked 2 important DNA repair pathways. To summarize, our study showed PLK1
      kinase as an option in the therapy of NSCLC.

PMID- 29040816
TI  - Lamin A/C mutation associated with lipodystrophy influences adipogenic
      differentiation of stem cells through interaction with Notch signaling.
AB  - Lamins A and C are involved in many cellular functions, owing to its ability to
      bind chromatin and transcription factors and affect their properties. Mutations
      of the LMNA gene encoding lamin A/C affect differentiation capacity of stem
      cells. However, the signaling pathways involved in interactions with lamins
      during cellular differentiation remain unclear. Lipodystrophy associated with
      LMNA mutation R482L causes loss of fat tissue. In this study we investigated the
      role of LMNA mutation R482L in modulating Notch signaling activity in the
      adipogenic differentiation of mesenchymal stem cells. Notch was activated using
      lentiviral Notch intracellular domain. Activation of Notch was estimated through
      the expression of Notch-responsive genes by qPCR and by activation of a
      luciferase CSL-reporter construct. The effect of LMNA mutation on Notch
      activation and adipogenic differentiation was analyzed in cells bearing
      lentiviral LMNA WT or LMNA R482L. We show that, when Notch is activated, LMNA
      R482L contributes to down-regulation of Notch activation in undifferentiated and
      differentiated cells, and decreases adipogenic differentiation. Thus, lamin A/C
      interacts with Notch signaling, thereby influencing cellular differentiation, and
      point mutation in LMNA could halt this interaction.

PMID- 29040815
TI  - The role of folic acid and selenium against oxidative damage from ethanol in
      early life programming: a review.
AB  - There are disorders in children, covered by the umbrella term "fetal alcohol
      spectrum disorder" (FASD), that occur as result of alcohol consumption during
      pregnancy and lactation. They appear, at least in part, to be related to the
      oxidative stress generated by ethanol. Ethanol metabolism generates reactive
      oxygen species and depletes the antioxidant molecule glutathione (GSH), leading
      to oxidative stress and lipid and protein damage, which are related to growth
      retardation and neurotoxicity, thereby increasing the incidence of FASD.
      Furthermore, prenatal and postnatal exposure to ethanol in dams, as well as
      increasing oxidation in offspring, causes malnutrition of several micronutrients
      such as the antioxidant folic acid and selenium (Se), affecting their metabolism
      and bodily distribution. Although abstinence from alcohol is the only way to
      prevent FASD, it is possible to reduce its harmful effects with a maternal
      dietary antioxidant therapy. In this review, folic acid and Se have been chosen
      to be analyzed as antioxidant intervention systems related to FASD because, like
      ethanol, they act on the methionine metabolic cycle, being related to the
      endogenous antioxidants GSH and glutathione peroxidase. Moreover, several birth
      defects are related to poor folate and Se status.

PMID- 29040817
TI  - Potential for mcl-PHA production from nonanoic and azelaic acids.
AB  - Greater than 65% of canola and high-oleic soy oil fatty acids is oleic acid,
      which is readily converted to nonanoic (NA) and azelaic (AzA) acids by
      ozonolysis. NA is an excellent substrate for medium-chain-length
      polyhydroxyalkanoate (mcl-PHA) production but AzA has few uses. Pseudomonas
      citronellolis DSM 50332 and Pseudomonas fluorescens ATCC 17400, both able to
      produce mcl-PHA from fatty acids and to grow on AzA as the sole source of carbon
      and energy, were assessed for the accumulation of mcl-PHA from AzA and NA. In N
      limited shake flasks using NA, P. citronellolis produced 32% of its dry biomass
      as mcl-PHA containing 78% 3-hydroxynonanoate with 22% 3-hydroxyheptanoate.
      Pseudomonas fluorescens produced only 2% PHA. N-limited P. citronellolis on AzA
      produced 20% dry weight PHA containing 75% 3-hydroxydecanoate and 25% 3
      hydroxyoctanoate, indicative of de novo synthesis. Although selective pressure,
      including beta-oxidation inhibition, under well-controlled (chemostat) conditions
      was applied to P. citronellolis, no side-chain carboxyl groups were detected. It
      was concluded that one or more of FabG and PhaJ or the PHA synthase cannot
      catalyze reactions involving omega-carboxy substrates. However, a process based
      on oleic acid could be established if Pseudomonas putida was engineered to grow
      on AzA.

PMID- 29040819
TI  - Velopharyngeal Insufficiency and Hypernasal Voice: 15 Years' Experience With
      Furlow Palatoplasty.

PMID- 29040818
TI  - Metformin attenuates ER stress-induced mitochondrial dysfunction.
AB  - Endoplasmic reticulum (ER) stress, a disturbance of the ER function, contributes
      to cardiac injury. ER and mitochondria are closely connected organelles within
      cells. ER stress contributes to mitochondrial dysfunction, which is a key factor
      to increase cardiac injury. Metformin, a traditional anti-diabetic drug,
      decreases cardiac injury during ischemia-reperfusion. Metformin also inhibits ER
      stress in cultured cells. We hypothesized that metformin can attenuate the ER
      stress-induced mitochondrial dysfunction and subsequent cardiac injury.
      Thapsigargin (THAP, 3 mg/kg) was used to induce ER stress in C57BL/6 mice. Cell
      injury and mitochondrial function were evaluated in the mouse heart 48 hours
      after 1-time THAP treatment. Metformin was dissolved in drinking water (0.5 g/250
      ml) and fed to mice for 7 days before THAP injection. Metformin feeding continued
      after THAP treatment. THAP treatment increased apoptosis in mouse myocardium
      compared to control. THAP also led to decreased oxidative phosphorylation in
      heart mitochondria-oxidizing complex I substrates. THAP decreased the calcium
      retention capacity, indicating that ER stress sensitizes mitochondria to
      mitochondrial permeability transition pore opening. The cytosolic C/EBP
      homologous protein (CHOP) content was markedly increased in THAP-treated hearts
      compared to control, particularly in the nucleus. Metformin prevented the THAP
      induced mitochondrial dysfunction and reduced CHOP content in cytosol and
      nucleus. Thus, metformin reduces cardiac injury during ER stress through the
      protection of cardiac mitochondria and attenuation of CHOP expression.

PMID- 29040821
TI  - Dietary Intake and Omega-3 DHA Status in Pregnant Women Who Are Overweight.
AB  - OBJECTIVE: To estimate dietary intake of pregnant women who are overweight,
      assess their omega-3 docosahexaenoic acid (DHA) status, and compare results
      between Black and White women. DESIGN: Cross-sectional study with a longitudinal
      component (dietary assessment). SETTING: Outpatient clinics at Woman's Hospital,
      Baton Rouge, Louisiana and telephone calls. PARTICIPANTS: Pregnant women (N = 21)
      who were overweight (body mass index = 25.0-29.9 kg/m2). METHODS: Repeated 24
      hour dietary recalls using the University of Minnesota Nutrition Data System for
      Research were conducted to determine nutrient intakes. Red blood cell fatty acids
      were analyzed with gas chromatography to determine omega-3 DHA status.
      Descriptive statistics, one- and two-sample t tests, Fisher's exact tests, chi
      square test, and analysis of covariance were used to analyze data. RESULTS: On
      average, participants consumed 72 +/- 63 mg omega-3 DHA/day. Age, race, and
      socioeconomic status did not affect the probability of achieving recommended
      omega-3 DHA dietary intake (p > .05). Black women had lower omega-3 DHA status
      (7.98 +/- 0.94 weight percentage) than White women (9.29 +/- 1.68 weight
      percentage; p <= .05). CONCLUSION: Analysis of our data suggests a need for
      nutrition education regarding the benefits of omega-3 DHA consumption during
      pregnancy for women of childbearing age. The current finding warrants further
      exploration.

PMID- 29040820
TI  - Systematic Review of the Effect of Enteral Feeding on Gut Microbiota in Preterm
      Infants.
AB  - OBJECTIVE: To examine the effect of feeding type on microbial patterns among
      preterm infants and to identify feeding factors that promote the colonization of
      beneficial bacteria. DATA SOURCES: PubMed, Cochrane Database of Systematic
      Reviews, Scopus, and the Cummulative Index of Nursing and Allied Health
      Literature were thoroughly searched for articles published between January 2000
      and January 2017, using the keywords gut microbiome, gut microbiota, enteral
      microbiome, enteral microbiota, premature infant, preterm infant, extremely low
      birth weight infant, ELBW infant, very low birth weight infant, feeding, breast
      milk, breastfeeding, formula, prebiotic, probiotic, and long chain
      polyunsaturated fatty acid. STUDY SELECTION: Primary studies written in English
      and focused on the association between enteral feeding and gut microbiome
      patterns of preterm infants were included in the review. DATA EXTRACTION: We
      independently reviewed the selected articles and extracted information using
      predefined data extraction criteria including study design, study participants,
      type of feeding, type and frequency of biospecimen (e.g., feces, gastric
      aspirate) collection, microbiological analysis method, and major results. DATA
      SYNTHESIS: In 4 of the 18 studies included in the review, researchers described
      the effects of milk products (mothers' own milk, donor human milk, and formula).
      In 5 studies, the effects of prebiotics were assessed, and in 9 studies, the
      effects of probiotics on the gut microbiome were described. Mothers' own breast
      milk feeding influenced the compositional structure of preterm infants' gut
      microbial community and increased diversity of gut microbiota compared with donor
      human milk and formula feeding. The results of the use of prebiotics and
      probiotics varied among studies; however, the majority of the researchers
      reported positive bifidogenic effects on the development of beneficial bacteria.
      CONCLUSION: Mothers' own milk is considered the best form of nutrition for
      preterm infants and the gut microbial community. Variation in fatty acid
      composition across infant feeding types can affect microbial composition. The
      evidence for supplementation of prebiotics and probiotics to promote the gut
      microbial community structure is compelling; however, additional research is
      needed in this area.

PMID- 29040822
TI  - Removal of lead and bisphenol A using magnesium silicate impregnated palm-shell
      waste powdered activated carbon: Comparative studies on single and binary
      pollutant adsorption.
AB  - In this work, palm shell waste powder activated carbon coated by magnesium
      silicate (PPAC-MS) were synthesized by the impregnation of magnesium silicate
      (MgSiO3) using economical material (silicon dioxide powder) via mild hydrothermal
      approach for the first time. As an effective adsorbent, PPAC-MS simultaneously
      removes BPA and Pb(II) in single and binary mode. Surprisingly, PPAC-MS exhibited
      a homogeneous thin plate mesh-like structure, as well as meso- and macropores
      with a high surface area of 772.1m2g-1. Due to its specific morphological
      characteristics, PPAC-MS had adsorption capacities of Pb(II) as high as 419.9mgg
      1 and 408.8mgg-1 in single mode and binary mode based on Freudliuch isotherm
      model while those for BPA by PPAC-MS were 168.4mgg-1 and 254.7mgg-1 for single
      mode and binary modes corresponding to Langmuir isotherm model. Experiment
      results also indicated that the synergistic removal of BPA occurred because the
      precipitation process of Pb(II) leads to the co-precipitation of BPA with Pb(OH)2
      compound. PPAC-MS showed a good reusability for 5 regeneration cycles using
      Mg(II) solution followed by thermal treatment. Overall, PPAC-MS has a high
      potential in the treatment process for wastewater containing both toxic heavy
      metals and emerging pollutants due to its high sorption capacities and
      reusability.

PMID- 29040823
TI  - Urea increased nickel and copper accumulation in the leaves of Egeria densa
      (Planch.) Casp. and Ceratophyllum demersum L. during short-term exposure.
AB  - In the present study, two fresh water plant species Egeria densa (Planch.) Casp.
      and Ceratophyllum demersum L. were subjected to separate and combined action of
      urea (2mM) and metals (Ni and Cu, 10MUM) to investigate the phytoremediation
      potential of these two submerged macrophytes during short-term experiments (48h).
      Both submerged macrophytes demonstrated high accumulative potential for Ni and Cu
      (average bioconcentration factors were 2505 for Ni and 3778 for Cu). The urea (2
      mM) was not significantly toxic for studied plant species. Futhermore, urea
      worked as an additional source of nitrogen and stimulated some metabolic
      processes such as the synthesis of photosynthetic pigments, soluble proteins, non
      enzymatic antioxidants, and activated some enzymes. Adding urea to the metals
      increased their accumulation in both macrophytes (on average by 35% for Ni and
      15% for Cu). Combined action of urea and Ni did not have a significant effect on
      antioxidant response, but caused a sharp increase of urease activity (4 folds on
      an average) in both plants. The copper exerted a stronger toxic effect on both
      studied macrophytes compared to nickel. Adding urea to copper in some cases
      diminished the toxic action of this metal. Study concludes that the responses of
      E. densa and C. demersum to urea and metal action (separate and combined) were
      depended on the type of pollutant and the activity of antioxidant defence system.
      Therefore, the studied aquatic macrophytes found to be potential phytoremediators
      of water bodies, the addition of an organic nitrogen source in the form of urea
      in environmentally relevant concentration will increase the efficiency of
      phytoextraction of metals.

PMID- 29040824
TI  - Perceived harm as a mediator of the relationship between social norms and
      marijuana use and related consequences among American Indian youth.
AB  - BACKGROUND: American Indian (AI) youth are at increased risk for marijuana use
      with marijuana use rates on or near reservations 1.6-4.8 times higher compared to
      non-AI youth in the same regions (Stanley et al., 2014). One outcome of the
      changing social and legal acceptance of marijuana is a decrease in perceived risk
      among adolescents. It is unknown whether these changes in perceptions of
      marijuana-related harm will presage higher rates of use among AI youth.
      Perceptions of others use (i.e., descriptive norms) and approval (i.e.,
      injunctive norms) are consistent predictors of marijuana use and consequences.
      Moreover, large scale surveys have shown that gender is an important moderator of
      the relationship between norms and marijuana use in AI samples. METHOD: The
      current study is a large epidemiologic study of 7th-12th grade self-identified
      American Indian students (N=3050). We examined the direct relations between
      descriptive and injunctive norms and marijuana use/consequences among AI youth,
      as well as the mediating role of perceived harm and the moderating role of
      gender. RESULTS: Results of a multi-group path analysis revealed a similar
      pattern of findings for males and females. In addition, there were direct effects
      for descriptive but not injunctive norms on marijuana use/consequences, and the
      sequential pathway from norms to use/consequences via perceived harm held.
      DISCUSSION: Findings suggest that normative perceptions and perceived harm are
      antecedents of marijuana use/consequences and are prime targets for large scale
      interventions on AI reservations.

PMID- 29040825
TI  - Comparing the predictive validity of the four-factor and five-factor (bifactor)
      measurement structures of the drinking motives questionnaire.
AB  - INTRODUCTION: The Drinking Motives Questionnaire (DMQ-R) is the most widely
      administered instrument to assess reasons for consuming alcohol and is
      conventionally premised on a four-factor structure. Recent research instead
      reveals that a bifactor measurement model of five motive factors (one general and
      four specific) represents a superior psychometric embodiment of the scale. The
      current study evaluated and compared the predictive validity of the four-factor
      and five-factor models of drinking motives in longitudinally explaining alcohol
      use and problems. METHODS: Adult participants (N=413; age range=18-79 years)
      completed measures of drinking motives (Time 1) and alcohol use and problems one
      month later (Time 2). RESULTS: Confirmatory factor analyses corroborated the four
      factor (social, enhancement, conformity, and coping motives) and five-factor
      (each item double loading on general motives and a specific motives factor)
      measurement structures, but the latter rendered stronger fit indices. Structural
      equation models revealed that lower social motives, higher enhancement motives,
      and higher coping motives prospectively contributed to alcohol use. Furthermore,
      lower social motives, higher conformity motives, higher coping motives, and
      greater alcohol use contributed to alcohol problems. DISCUSSION: The same set of
      paths emerged as significantly predictive in both models, but general motives
      additionally explained alcohol use and problems in the five-factor model. The
      incremental contribution of general motives (beyond the specific motives) on
      alcohol intake and detrimental consequences supports the predictive validity of
      the drinking reasons paradigm embodied by the inclusion of a global factor.

PMID- 29040826
TI  - Maintenance on naltrexone+amphetamine decreases cocaine-vs.-food choice in male
      rhesus monkeys.
AB  - BACKGROUND: Cocaine use disorder remains a significant public health issue for
      which there are no FDA-approved pharmacotherapies. Amphetamine maintenance
      reduces cocaine use in preclinical and clinical studies, but the mechanism of
      this effect is unknown. Previous studies indicate a role for endogenous opioid
      release and subsequent opioid receptor activation in some amphetamine effects;
      therefore, the current study examined the role of mu-opioid receptor activation
      in d-amphetamine treatment effects in an assay of cocaine-vs-food choice.
      METHODS: Adult male rhesus monkeys with double-lumen intravenous catheters
      responded for concurrently available food pellets and cocaine injections (0
      0.1mg/kg/injection) during daily sessions. Cocaine choice and overall
      reinforcement rates were evaluated during 7-day treatments with saline or test
      drugs. RESULTS: During saline treatment, cocaine maintained a dose-dependent
      increase in cocaine-vs.-food choice. The mu-opioid receptor agonist morphine
      (0.032-0.32mg/kg/h) dose-dependently increased cocaine choice and decreased rates
      of reinforcement. A dose of the mu-selective opioid receptor antagonist
      naltrexone (0.0032mg/kg/h) that completely blocked morphine effects had no effect
      on cocaine choice when it was administered alone, but it enhanced the
      effectiveness of a threshold dose of 0.032mg/kg/h amphetamine to decrease cocaine
      choice without also enhancing nonselective behavioral disruption by this dose of
      amphetamine. Conversely, the kappa-selective opioid antagonist norbinalorphimine
      did not enhance amphetamine effects on cocaine choice. CONCLUSIONS: These results
      suggest that amphetamine maintenance produces mu opioid-receptor mediated effects
      that oppose its anti-cocaine effects. Co-administration of naltrexone may
      selectively enhance amphetamine potency to decrease cocaine choice without
      increasing amphetamine potency to produce general behavioral disruption.

PMID- 29040828
TI  - Neuropsychological functioning and brain energetics of drug resistant mesial
      temporal lobe epilepsy patients.
AB  - Interictal hypometabolism is commonly measured by 18-fluoro-deoxyglucose Positron
      Emission Tomography (FDG-PET) in the temporal lobe of patients with mesial
      temporal lobe epilepsy (MTLE-HS). Left temporal lobe interictal FDG-PET
      hypometabolism has been associated with verbal memory impairment, while right
      temporal lobe FDG-PET hypometabolism is associated with nonverbal memory
      impairment. The biochemical mechanisms involved in these findings remain unknown.
      In comparison to healthy controls (n=21), surgically treated patients with MTLE
      HS (n=32, left side=17) had significant lower scores in the Rey Auditory Verbal
      Learning Test (RAVLT retention and delayed), Logical Memory II (LMII), Boston
      Naming test (BNT), Letter Fluency and Category Fluency. We investigated whether
      enzymatic activities of the mitochondrial enzymes Complex I (C I), Complex II (C
      II), Complex IV (C IV) and Succinate Dehydrogenase (SDH) from the resected
      samples of the middle temporal neocortex (mTCx), amygdala (AMY) and hippocampus
      (HIP) were associated with performance in the RAVLT, LMII, BNT and fluency tests
      of our patients. After controlling for the side of hippocampus sclerosis, years
      of education, disease duration, antiepileptic treatment and seizure outcome after
      surgery, no independent associations were observed between the cognitive test
      scores and the analyzed mitochondrial enzymatic activities (p>0.37). Results
      indicate that memory and language impairment observed in MTLE-HS patients are not
      strongly associated with the levels of mitochondrial CI, CII, SDH and C IV
      enzymatic activities in the temporal lobe structures ipsilateral to the HS
      lesion.

PMID- 29040827
TI  - Effects of lorcaserin (Belviq(r)) on nicotine- and food-maintained responding in
      non-human primates.
AB  - BACKGROUND: Accumulating evidence suggests that the FDA-approved serotonin 5-HT2C
      receptor agonist, lorcaserin (Belviq(r)), may be a promising candidate for the
      management of substance use disorders, including nicotine addiction. The present
      study was conducted to determine the efficacy and selectivity of acute or
      continuous lorcaserin treatment for decreasing the reinforcing effects of
      nicotine in a primate species. METHODS: Adult rhesus monkeys (n=4) with a history
      of nicotine self-administration (>2years) responded for injections of nicotine
      (0.32-100MUg/kg IV) or food pellets under a fixed-ratio schedule of reinforcement
      during daily 100-min sessions. When responding was stable, lorcaserin was
      administered either as an acute pretreatment (0.1-1.0mg/kg, IM) or by continuous
      infusion (0.1mg/kg/hr, SC for 3-5days). Daily activity patterns were also
      monitored immediately following experimental sessions. RESULTS: Results indicate
      that acute lorcaserin pretreatment produced significant and dose-dependent
      decreases in nicotine-maintained responding across a >100-fold range of self
      administered nicotine doses. Continuous lorcaserin treatment decreased intake of
      10MUg/kg/inj nicotine to about 50% of baseline values. Food-maintained responding
      was only moderately decreased in 3 of 4 subjects after acute administration and
      unaffected in all subjects during continuous treatment. Daily activity also was
      significantly decreased-to <=50% of control values-following experimental
      sessions in which acute lorcaserin was administered. CONCLUSIONS: These data
      indicate that lorcaserin reduces IV self-administration of nicotine at a dose
      that decreases motoric activity but less consistently disrupts food-maintained
      responding. Further research into lorcaserin's potential utility for the
      management of nicotine dependence is warranted.

PMID- 29040829
TI  - Soybean-derived Bowman-Birk inhibitor (BBI) blocks HIV entry into macrophages.
AB  - Bowman-Birk inhibitor (BBI) is a soybean-derived protease inhibitor that has anti
      inflammation and anti-HIV effect. Here, we further investigated the anti-HIV
      action of BBI in macrophages, focusing on its effect on viral entry. We found
      that BBI could significantly block HIV entry into macrophages. Investigation of
      the mechanism(s) of the BBI action on HIV inhibition showed that BBI down
      regulated the expression of CD4 receptor (as much as 80%) and induced the
      production of the CC chemokines (up to 60 folds at protein level) in macrophages.
      This inhibitory effect of BBI on HIV entry could be blocked by the neutralization
      antibodies to CC chemokines. These findings indicate that BBI may have
      therapeutic potential as a viral entry inhibitor for the prevention and treatment
      of HIV infection.

PMID- 29040830
TI  - Combined toxicity of prevalent mycotoxins studied in fish cell line and zebrafish
      larvae revealed that type of interactions is dose-dependent.
AB  - While, Aflatoxin B1 (AFB1), deoxynivalenol (DON) and zearalenone (ZEN) are the
      most prevalent mycotoxins co-existing in grain products and animal feeds, little
      is known about their combinatorial toxicities on aquatic life-forms. We studied
      the individual and combined effects of these mycotoxins in a fish cell line (BF
      2) and zebrafish larvae (wild-type and transgenic). The types of interactions in
      mycotoxins combinations on cell viability were determined by using Chou-Talalay
      model. Induction of oxidative stress pathway in mycotoxins-exposed BF-2 cells was
      assessed using high content screening (HCS). Mycotoxin-exposed wild-type
      zebrafish larvae were examined for mortality and morphological abnormalities and
      transgenic zebrafish larvae (expressing DsRed in the liver) were imaged using HCS
      and examined for liver abnormalities. Results showed that the cytotoxicity of
      mycotoxins in a decreasing order was AFB1>DON>ZEN, however, the highest mortality
      rate and liver damage in zebrafish were observed for AFB1 followed by ZEN.
      AFB1+DON and AFB1+ZEN synergistically enhanced the toxic effects on BF-2 cells
      and zebrafish while DON+ZEN showed antagonism. Interestingly, in the tertiary
      combination, the synergism seen at lower individual concentrations of mycotoxins
      progressively turned to an overall antagonism at higher doses. The results
      provide a scientific basis for the necessity to consider co-exposure when
      formulating risk-management strategies.

PMID- 29040831
TI  - Synergy in thrombin-graphene sponge for improved hemostatic efficacy and facile
      utilization.
AB  - Composites are attractive for its potential synergistic effects that can result
      in high-performance, but the synergy depends on subtle design. In this study, a
      hemostatic composite, a thrombin/cross-linked graphene sponge (TCGS), was
      developed through a facile gradient composite strategy. The porous structure of
      the CGS assures that the thrombin is stably embedded in the TCGS, avoiding a
      burst release but maintaining its bioactivity. In the synergy between proper
      thrombin stimulation and the fast absorption of the sponge, TCGS exhibits
      outstanding hemostatic performance, ultrafast bleeding cessation, within 100s,
      which is superior to both CGS and equal amounts of native thrombin. Lower or
      excessive thrombin dosages prolong the bleeding time. The study revealed that the
      balance between plasma absorption and thrombin stimulation at the interface is
      critical for improving hemostatic efficacy. TCGS is also highlighted for its
      biosafety and stability, even after 6 months of storage in environment. This
      potentially ultra-long shelf life is conducive to its practical applications.
      Therefore, TCGS not only provides a new strategy for developing a hemostatic
      composite but also provides a new method and understanding for the design of
      hemostatic materials.

PMID- 29040832
TI  - Biological evaluation of surface-modified magnetic nanoparticles as a platform
      for colon cancer cell theranostics.
AB  - Magnetic nanoparticles offer multiple possibilities for biomedical applications.
      Besides their physico-chemical properties, nanoparticle-cellular interactions are
      determinant for biological safety. In this work, magnetic nanoparticles were
      synthesized by one-shot precipitation or two-step reaction and coated with
      biocompatible polymers, such as poly(l-lysine) and poly(N,N-dimethylacrylamide-co
      acrylic acid), and carbohydrates, like l-ascorbic acid, d-galactose, d-mannose,
      and sucrose. The resulting magnetic nanoparticles were characterized by dynamic
      light scattering, FT-Raman spectroscopy, transmission electron microscopy, SQUID
      magnetometry, and Mossbauer spectroscopy. Ability of the nanoparticles to be used
      in theranostic applications was also evaluated, showing that coating with
      biocompatible polymers increased the heating efficiency. Nanoparticles
      synthesized by one-shot precipitation were 50% larger (~13nm) than those obtained
      by a two-step reaction (~8nm). Magnetic nanoparticles at concentrations up to
      500MUgmL-1 were non-cytotoxic to L929 fibroblasts. Particles synthesized by one
      shot precipitation had little effect on viability, cell cycle and apoptosis of
      the three human colon cancer cell lines used: Caco-2, HT-29, and SW-480. At the
      same concentration (500MUgmL-1), magnetic particles prepared by a two-step
      reaction reduced colon cancer cell viability by 20%, affecting cell cycle and
      inducing cell apoptosis. Uptake of surface-coated magnetic nanoparticles by colon
      cancer cells was dependent on particle synthesis, surface coating and incubation
      time.

PMID- 29040833
TI  - A novel approach for UV-patterning with binary polymer brushes.
AB  - A mixed self-assembled monolayer (SAM) of an initiator (3-(2-bromo-2
      isobutyryloxy)propyl triethoxysilane) for atom transfer radical polymerization
      (ATRP) and an agent (6-(triethoxysilyl)hexyl 2-(((methylthio)carbonothioyl)thio)
      2-phenylacetate) for reversible addition-fragmentation chain transfer (RAFT)
      polymerization was constructed on the surface of a silicon wafer or glass plate
      by a silane coupling reaction. When a UV light at 254nm was irradiated at the
      mixed SAM through a photomask, the surface density of the bromine atom at the end
      of BPE in the irradiated region was drastically reduced by UV-driven scission of
      the BrC bond, as observed by X-ray photoelectron spectroscopy. Consequently, the
      surface-initiated (SI)-ATRP of 2-ethylhexyl methacrylate (EHMA) was used to
      easily construct the poly(EHMA) (PEHMA) brush domain. Subsequently, SI-RAFT
      polymerization of a zwitterionic vinyl monomer, carboxymethyl betaine (CMB), was
      performed. Using the sequential polymerization, the PCMB and PEHMA brush domains
      on the solid substrate could be very easily patterned. Patterning proteins and
      cells with the binary polymer brush is expected because the PCMB brush indicated
      strong suppression of protein adsorption and cell adhesion, and the PEHMA brush
      had non-polar properties. This technique is very simple and useful for regulating
      the shape and size of bio-fouling and anti-biofouling domains on solid surfaces.

PMID- 29040834
TI  - Effect of oil structure on cyclodextrin-based Pickering emulsions for bupivacaine
      topical application.
AB  - Cyclodextrins (CDs) coupled with oils forms an insoluble inclusion complex that
      is able to adsorb to the interface between oils and aqueous phases; it thereby
      stabilizes Pickering emulsions. Three types of oils (triglyceride, linear chain
      oil, and ring-structured oil) were chosen to work with CDs to prepare bupivacaine
      (BPC)-encapsulated Pickering emulsions. We also investigated the relationship
      between oils and CDs; as well as their influences on stability, drug-releasing
      capability and skin permeability. Particle sizes and microstructures were
      determined by dynamic light scattering and scanning electron microscopy,
      respectively. In vitro drug release studies and in vitro skin permeation studies
      were evaluated by using Franz diffusion model. Particle sizes of all Pickering
      emulsions were larger than 1MUm, and the morphology was spherical and covered
      with rough surfaces. BPC was released over an extended period, and the releasing
      ratios from Pickering emulsions were only 12.2%-23.1% after 48h. In skin
      permeation studies, compared with other formulations, a formula involved with
      ring-structured oil allowed the highest permeation amount through skin. However,
      after 24h of exposure, formulation operated with linear chain oil showed the
      highest skin-retaining amount. These results suggest that Pickering emulsions
      could regulate the target site of skin depending on various types of oil used.

PMID- 29040835
TI  - Effects of sodium beta-sitosteryl sulfate on the phase behavior of
      dipalmitoylphosphatidylcholine.
AB  - We have studied the phase behavior of dipalmitoylphosphatidylcholine (DPPC)
      containing sodium beta-sitosteryl sulfate (PSO4). PSO4 was found to lower the
      phase transition temperature of DPPC to a higher degree than cholesterol or beta
      sitosterol. It also gave rise to the formation of a modulated (ripple) phase
      (Pbeta) at low to moderate concentrations. At concentrations greater than 25
      mol%, it completely changed the membrane into a fluid phase. This shows that PSO4
      is capable of disordering the hydrocarbon chains of PC efficiently. The
      characteristics of PSO4 for fluidizing the membrane can be useful for the
      pharmaceutical and cosmetics industries.

PMID- 29040836
TI  - Surface-modified PLGA nanoparticles with chitosan for oral delivery of
      tolbutamide.
AB  - The main purpose of present study was to develop novel chitosan-modified
      polylactic-co-glycolicacid nanoparticles (CS@PLGA NPs) for improving the bio
      availability of tolbutamide (TOL). The TOL-loaded CS@PLGA NPs (TOL-CS@PLGA NPs)
      were fabricated with the solvent evaporation method. The cargo-free CS@PLGA NPs
      showed a diameter of 228.3+/-2.5nm monitored with a laser light particlesizer,
      and the transmission electron microscope (TEM) photographs revealed their "core
      shell" structures. The Zeta potential of the original PLGA NPs and the cargo-free
      CS@PLGA NPs was measured to be -20.2+/-3.21mV and 24.2+/-1.1mV, respectively. The
      changes in Zeta potential indicated the CS chains were coated on the surfaces of
      the original PLGA NPs. The thermal gravity analysis (TGA) curves suggested that
      the CS chains improved the thermostability of the original PLGA NPs. The results
      of cells viability indicated the cargo-free CS@PLGA NPs were nontoxicity. The in
      vitro release profiles suggested that TOL-CS@PLGA NPs could release TOL in pH 7.4
      phosphate buffer solution (PBS) at a sustained manner. Streptozotocin (STZ) was
      employed to build the diabetic rat models. The physiological changes in the islet
      beta cells confirmed the obtaining of diabetic rats. After treatment by gavage,
      the TOL-CS@PLGA NPs showed an excellent hypoglycemic effect. Therefore, the TOL
      CS@PLGA NPs had a potential application in oral delivery of TOL.

PMID- 29040837
TI  - Grape intake reduces thrombin generation and enhances plasma fibrinolysis.
      Potential role of circulating procoagulant microparticles.
AB  - Phytochemicals contained in grapes down-regulate several prothrombotic pathways
      in vitro. We evaluated the effect of grape consumption on coagulation and
      fibrinolysis in healthy volunteers. Thirty subjects were enrolled: 20 were given
      grape (5 g/kg body weight/day for 3 weeks), while 10 served as controls. Blood
      samples were taken at baseline (T0), at the end of the grape diet (T1) and after
      4-week wash-out (T2). Grape intake caused a significant decrease of the
      procoagulant and inflammatory responses of whole blood and/or mononuclear cells
      to bacterial lipopolysaccharide at both T1 and T2. At plasma level, grape diet
      decreased thrombin generation at T1 and T2, largely through a reduction in the
      number and/or activity of procoagulant microparticles. This anticoagulant effect
      resulted in the formation of clots that were more susceptible to fibrinolysis,
      mainly because of a lesser activation of thrombin activatable fibrinolysis
      inhibitor. No difference in any variables was detected in controls at the time
      points considered. In conclusion, chronic grape consumption induces sustained
      anticoagulant and profibrinolytic effects with potential benefits for human
      health.

PMID- 29040838
TI  - Nutrient sensing and metabolic changes after methionine deprivation in primary
      muscle cells of turbot (Scophthalmus maximus L.).
AB  - The low methionine content in plant-based diets is a major limiting factor for
      feed utilization by animals. However, the molecular consequences triggered by
      methionine deficiency have not been well characterized, especially in fish
      species, whose metabolism is unique in many aspects and important for aquaculture
      industry. In the present study, the primary muscle cells of turbot (Scophthalmus
      maximus L.) were isolated and treated with or without methionine for 12 h in
      culture. The responses of nutrient sensing pathways, the proteomic profiling of
      metabolic processes, and the expressions of key metabolic molecules were
      systematically examined. Methionine deprivation (MD) suppressed target of
      rapamycin (TOR) signaling, activated AMP-activated protein kinase (AMPK) and
      amino acid response (AAR) pathways. Reduced cellular protein synthesis and
      increased protein degradation by MD led to increased intracellular free amino
      acid levels and degradations. MD also reduced glycolysis and lipogenesis while
      stimulated lipolysis, thus resulted in decreased intracellular lipid pool. MD
      significantly enhanced energy expenditure through stimulated tricarboxylic acid
      (TCA) cycle and oxidative phosphorylation. Collectively, our results identified a
      comprehensive set of transcriptional, proteomic, and signaling responses
      generated by MD and provided the molecular insight into the integration of cell
      homeostasis and metabolic controls in fish species.

PMID- 29040839
TI  - Effects of the dietary carbohydrate-fat ratio on plasma phosphatidylcholine
      profiles in human and mouse.
AB  - Phosphatidylcholines (PCs), a major class of human plasma phospholipids, are
      composed of highly diverse fatty acids. Because the dietary carbohydrate-fat
      ratio alters the hepatic fatty acid metabolism, plasma fatty acids that bind PCs,
      which are secreted as lipoproteins from the liver, may be affected by long-term
      consumption of a high-carbohydrate diet or a high-fat diet. Therefore, in this
      study, we profiled the plasma PC species comprehensively in formulated dieting
      conditions to identify those phospholipid molecules that reflect the dietary
      carbohydrate-fat ratio. C57BL6J mice were fed diets containing different amounts
      of fat for 8 weeks, and plasma PC species were analyzed under fasting conditions
      using liquid chromatography-mass spectrometry. In addition, a cross-sectional
      study of 78 middle-aged Japanese men, who participated in health checkups, was
      conducted. Nutrient intakes were estimated by a brief self-administered diet
      history questionnaire. The plasma PC profiles changed depending on the dietary
      carbohydrate-fat ratio. Especially, PC (16:0/16:1) and PC (16:0/18:1) levels
      increased as the dietary carbohydrate-fat ratio increased in human and mouse,
      suggesting that these PC species reflected the increase in de novo lipogenesis
      and might become useful biomarkers of the dietary carbohydrate-fat ratio. Since
      these PCs act as ligands for peroxisome proliferator-activated receptor alpha, PC
      species reflecting the dietary carbohydrate-fat ratio may influence metabolism of
      glucose and lipids.

PMID- 29040840
TI  - Experiences of structural vulnerability among exotic dancers in Baltimore,
      Maryland: Co-occurring social and economic antecedents of HIV/STI risk.
AB  - BACKGROUND: Women who grow up in economic scarcity often face limited
      opportunities for upward mobility, as a result of challenges securing stable
      housing, quality education, and steady employment. Chronic instability may limit
      the capacity of women to protect themselves against HIV/STI-related harm when
      engaging in sexual activity or drug use. Characterizing the structural contexts
      that facilitate HIV/STI risk among women are critical to effective design and
      implementation of drug and sexual harm reduction interventions. METHODS: Semi
      structured in-depth interviews were completed with 25 female exotic dancers
      working in Baltimore City and County exotic dance clubs July 2014-May 2015. Using
      thematic analysis, interviews were examined to understand the nature of
      structural vulnerability experienced by dancers during their early lives through
      the initial months of exotic dancing, including an examination of the roles of
      drug use and social relationships in engagement of sexual risk behavior. RESULTS:
      Dancers depicted early experiences of social and economic disadvantage, which
      accumulated through early adulthood. Substance use emerged as an important
      subject for the majority of women, operating cyclically as both precursor to and
      product of accumulating social and economic hardship. Dancers revealed social
      strategies that buffered the effects of structural vulnerability and minimized
      exposure to workplace-related drug and sexual harms. CONCLUSION: This study
      provides insight on an understudied group of at-risk women with a unique
      demographic profile. Findings illustrate how the effects of structural
      vulnerability, substance abuse, social strategies, and opportunities for economic
      gain through sexual services in the workplace converge to produce varying levels
      of HIV/STI risk among exotic dancers.

PMID- 29040841
TI  - "Caught with a body" yet protected by law? Calling 911 for opioid overdose in the
      context of the Good Samaritan Law.
AB  - BACKGROUND: To address soaring opioid overdose fatality rates, 41U.S. states have
      passed Good Samaritan Laws (GSLs) extending legal immunity to overdose bystanders
      who call for emergency assistance. This study, conducted during the period that
      followed implementation of a GSL, aimed to characterize current factors
      determining the decision to call for emergency medical help (911) at the scene of
      an overdose with specific attention to exploring the role of the GSL as one such
      factor in decision-making. METHODS: We conducted 22 in-depth interviews with
      needle exchange program clients in Baltimore, MD. RESULTS: Most participants
      reported calling 911 or witnessing a 911 call after drug overdose, but widely
      remained fearful of arrest for drug or paraphernalia possession, homicide,
      outstanding warrants, and/or trespassing. These concerns were underpinned by a
      history of police maltreatment and threat, and strong distrust of police;
      concerns which were specifically related to perceptions of police conduct at the
      scene of an overdose as well as perceptions of police conduct in general.
      Additional considerations included: fear of losing housing, informal shelter or
      custody of children; encountering social stigma; and facing violent and fatal
      repercussions at the hands of local drug dealers. Additionally, some participants
      did not perceive a significant enough medical risk to call 911. Two thirds of
      participants were unaware of the GSL. Some believed a GSL would positively impact
      law enforcement behaviour and increase the likelihood of a bystander call; but
      due to distrust of police, others believed the GSL would have little influence on
      bystander decisions. CONCLUSION: Insights from overdose bystanders during the
      post-implementation period of a Good Samaritan Law demonstrate persistent
      deterrents to bystanders calling 911 after overdose. Additional measures are
      needed to align policy aims with lived experiences of overdose bystanders, and to
      achieve overdose prevention aims.

PMID- 29040842
TI  - Cytotoxic dihydrobenzofuran neolignans from Mappianthus iodoies.
AB  - Three new dihydrobenzofuran neolignans, mappiodoinins A-C (1-3), together with
      nine known analogues (4 -12) were isolated from the stems and leaves of
      Mappianthus iodoies. Their structures with the absolute configurations were
      elucidated by extensive spectroscopic methods. This is the first time to find
      dihydrobenzofuran neolignans from the genus Mappianthus. All isolated compounds
      were evaluated for their cytotoxicities against five human cancer cell lines: HL
      60, SMMC-7721, A-549, MCF-7 and SW-480 in vitro. Neolignans 1-12 showed
      significant cytotoxic effects against various human cancer cell lines with IC50
      values ranging from 0.16 to 18.62 MUM.

PMID- 29040843
TI  - Characterization of EPS compositions and microbial community in an Anammox SBBR
      system treating landfill leachate.
AB  - The biofilm system is beneficial for Anammox process designed to treat landfill
      leachate. In this study, the composition of extracellular polymeric substances
      (EPS) and the microbial community in an Anammox biofilm system were analyzed to
      determine the functions driving the biofilm's ability to treat landfill leachate.
      The results demonstrated that increasing influent carbon oxygen demand (COD)
      could stimulate EPS production. EPS helped enrich Anammox bacteria and supplied
      them with nutrients and enzymes, facilitating effective nitrogen removal
      (approximately 95%). The variation in Anammox bacteria was similar to the
      variation in EPS composition. In the tested Anammox Sequencing Biofilm Batch
      Reactor (SBBR) system, Candidatus Kuenenia was dominant among known Anammox
      genus, because of its high substrate affinity and because it adapts better to
      landfill leachate. The relative abundance of Candidatus Kuenenia in the biofilm
      rose from 3.26% to 12.38%, illustrating the protection and enrichment offered by
      the biofilm in carrying out Anammox.

PMID- 29040844
TI  - Can hydrothermal pretreatment improve anaerobic digestion for biogas from
      lignocellulosic biomass?
AB  - Hydrothermally-pretreated rice straw (HPRS) from various pretreatment
      temperatures was anaerobically-digested in whole slurry. Results indicated
      promoting pretreatment temperature significantly deconstructed rice straw, and
      facilitated the conversion of insoluble fractions to soluble fractions. Although
      306.6 mL/g TS biogas was maximally yielded in HPRS-90 and HPRS-180, respectively,
      via digestion in whole slurry, it was only 3% promotion compared to the
      unpretreated rice straw. HPRS-210 yielded 208.5 mL/g TS biogas, which was 30%
      reduction with longer lag period of 19.8 d, suggesting serious inhibitions
      happened. Through slightly increasing organic loading, more serious acidification
      and reduction on biogas yield, especially at higher pretreatment temperatures,
      indicated the soluble fractions controlled digestion performances. Pearson
      correlation analysis suggested negative relationship existed between methane
      yield and the soluble fractions including soluble carbohydrates, formic acid and
      furfural. Hydrothermal pretreatment, especially at higher temperature, did not
      improve anaerobic digestion, thereby, was not recommended, however, lower
      temperature can be considered potentially.

PMID- 29040845
TI  - In-situ regeneration of activated carbon with electric potential swing desorption
      (EPSD) for the H2S removal from biogas.
AB  - In-situ regeneration of a granular activated carbon was conducted for the first
      time using electric potential swing desorption (EPSD) with potentials up to 30 V.
      The EPSD system was compared against a standard non-potential system using a
      fixed-bed reactor with a bed of 10 g of activated carbon treating a gas mixture
      with 10,000 ppm H2S. Breakthrough times, adsorption desorption volume,
      capacities, effect of regeneration and desorption kinetics were investigated. The
      analysis showed that desorption of H2S using the new EPSD system was 3 times
      quicker compared with the no potential system. Hence, physical adsorption using
      EPSD over activated carbon is efficient, safe and environmental friendly and
      could be used for the in-situ regeneration of granular activated carbon without
      using a PSA and/or TSA system. Additionally, adsorption and desorption cycles can
      be obtained with a classical two column system, which could lead towards a more
      efficient and economic biogas to biomethane process.

PMID- 29040846
TI  - Salt-tolerance aerobic granular sludge: Formation and microbial community
      characteristics.
AB  - The salt-tolerance aerobic granular sludge (SAGS) dominated by moderately
      halophilic bacteria was successfully cultured in a 9% (w/v) salty, lab-scale
      sequence batch reactor (SBR) system. Influence of high salinity (0-9% w/v NaCl)
      on the formation, performance and microbial succession of the SAGS were explored.
      Crystal nucleus hypothesis, selection pressure hypothesis and compressed double
      electric layers hypothesis were used to discuss the formation mechanism of SAGS.
      Notably, salinity could be seen as a kind of selection pressure contributed to
      the formation of SAGS, while salinity also declined the performance of SAGS
      system. High throughput 16S rRNA gene analysis showed that the salinity had great
      influence on the species succession and community structure of SAGS. Moreover,
      Salinicola and Halomonas were dominant at 9% salt concentration, therefore
      moderate halophiles were identified as functional groups for the tolerance of
      hypersaline stress.

PMID- 29040847
TI  - Characterization of ionic liquid pretreated plant cell wall for improved
      enzymatic digestibility.
AB  - An insight into the properties of cell wall of mustard stalk (MS) pretreated by
      five ionic liquids (ILs) revealed ILs interaction with cellulose, hemicellulose
      and lignin components. Differential Scanning Calorimetry (DSC) showed increased
      pore size coupled with increased population of pores evoked by certain ILs in
      better facilitating enzymatic accessibility. Interestingly, all the five ILs
      predominantly increased the propensity of two pore sizes formation; 19 and 198
      nm, but remarkable difference in the pore volumes of pretreated MS suggested the
      supremacy of [OAc]- based ILs, resulting in higher glucose yields. Cellulose I to
      II transition in pretreated MS was supported by the reduced total crystallinity
      index (TCI), lateral order index (LOI) values. Strong inverse correlation existed
      between the said parameters and residual acetyl content with enzymatic hydrolysis
      (R2 > 0.8). An inverse relationship between hydrogen bond basicity, LOI and TCI
      suggested it to be a good indicator of IL pretreatment efficiency.

PMID- 29040848
TI  - Responses of microbial community to pH stress in bioleaching of low grade copper
      sulfide.
AB  - The microbial diversity and dynamics in the leachates and on the ore surfaces of
      different depth of the column were analyzed during bioleaching of low grade
      copper sulfide at different pH, after inoculation with the same inoculum
      containing mesophiles and moderate thermophiles. The results indicate that low pH
      was beneficial to enhance copper extraction. The highest copper extraction (86%)
      was obtained when pH was controlled at 1.0-1.5. The microbial structures on the
      ore surfaces were independent of community structures in the leachate, even at
      the top portion of column. Microbial richness and evenness increased with
      decreasing pH during bioleaching. pH had significant effects on microbial
      community structure in the leachate and on the mineral surface of different depth
      of the column. Leptospirillum ferriphilum accounted for the highest proportions
      of the community at most times when pH was operated during bioleaching,
      especially at the end of run.

PMID- 29040849
TI  - Synergy of lignocelluloses pretreatment by sodium carbonate and bacterium to
      enhance enzymatic hydrolysis of rice straw.
AB  - We studied a new strategy for pretreatment of rice straw (RS) to enhance
      enzymatic hydrolysis under mild condition. This approach uses the synergy of
      sodium carbonate (Na2CO3) and the bacterial strain Cupriavidus basilensis B-8
      (hereafter B-8). After synergistic Na2CO3 and B-8 pretreatment (SNBP), the
      reducing sugar yield varied from 335.3mg/g to 799.6mg/g under different
      conditions. This increased by 13-31% over Na2CO3 pretreatment (284.2-719.2mg/g)
      and 3.42-8.15times over the untreated RS (98mg/g). Moreover, the composition of
      RS was changed significantly through decreases in lignin and hemicellulose. We
      confirmed this change by compositional analysis and physicochemical
      characterization of the structure of RS before and after pretreatment. We also
      elaborated a mechanism for SNBP to better explain RS changes and bacterial
      effects on enzymatic hydrolysis.

PMID- 29040850
TI  - Biosynthesis of tert-butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate by carbonyl
      reductase from Rhodosporidium toruloides in mono and biphasic media.
AB  - tert-Butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate ((3R,5S)-CDHH) is the key
      intermediate for synthesis of atorvastatin and rosuvastatin. Carbonyl reductase
      exhibits excellent activity toward tert-butyl (S)-6-chloro-5-hydroxy-3
      oxohexanoate ((S)-CHOH) to synthesize (3R,5S)-CDHH. In this study, a whole cell
      biosynthesis reaction system to produce (3R,5S)-CDHH was constructed in organic
      solvents. A solution of 10% (v/v) Tween-80 was introduced to the reaction system
      as a co-solvent, which greatly enhanced biotransformation process, giving 98.9%
      yield, >99% ee and 1.8-fold higher space time yield in 5 h bioconversion of 1 M
      (S)-CHOH, compared with 98.7% yield and >99% ee in 9 h bioconversion of a purely
      aqueous reaction system. Moreover, a water-octanol biphasic reaction system was
      built and 20% of octanol was added as reservoir of substrate resulting in 98%
      yield, >99% ee and 4.08 mmol L-1 h-1 g-1 (wet cell weight) space time yield. This
      study paved a way for the whole cell biosynthesis of (3R,5S)-CDHH in mono and
      biphasic media.

PMID- 29040851
TI  - Magnetic field action on outdoor and indoor cultures of Spirulina: Evaluation of
      growth, medium consumption and protein profile.
AB  - This study aimed at evaluating whether a magnetic field (MF) affects the growth
      of Spirulina sp. when applied to it at different exposure times in indoor and
      outdoor culture systems. The effects of MF on chlorophyll content, medium
      consumption and protein profile were also investigated. In raceway tanks, a 25 mT
      MF was applied for 24 h or for 1 h d-1. MF for 24 h to outdoor assays increased
      biomass concentration and chlorophyll-a content besides altering the protein
      profile. Outdoor Spirulina growth was higher (~3.65 g L-1) than the growth found
      in indoor assays (~1.80 g L-1), while nitrogen and phosphorus consumption was not
      enhanced by the application of MF. This is the first study that investigated the
      influence of MF on outdoor microalga assays, and the results showed that MF
      affected the metabolism of Spirulina cultured in raceways, especially when it was
      grown outdoors in uncontrolled environmental conditions.

PMID- 29040852
TI  - Blackwater treatment using vertical greening: Efficiency and microbial community
      structure.
AB  - This study assesses the use of vertical greening for blackwater treatment. The
      effects of hydraulic retention time (HRT) and drip frequency on treatment
      performance were systematically studied. Additionally, microbial communities in
      the vertical greening system were characterized. The results show that the
      removal efficiencies of NH4+-N and total phosphate (TP) increased with an
      increase in HRT, and the drip frequency had a significant effect on TP. High
      throughput sequencing revealed that the diversity of the microbial community did
      not change significantly along vertical and horizontal directions, but the
      dominant species shifted. Heterotrophic nitrifying and denitrifying bacteria
      decreased significantly while autotrophic nitrifying bacteria, especially ammonia
      oxidizing bacteria, proliferated in a vertical direction. Therefore, it is
      concluded that vertical greening systems can effectively treat blackwater and
      lower NH+-N levels.

PMID- 29040853
TI  - Chinese medicinal herbal residues as a bulking agent for food waste composting.
AB  - This study aimed to co-compost Chinese medicinal herbal residues (CMHRs) as the
      bulking agent with food waste (FW) to develop a high value antipathogenic
      compost. The FW, sawdust (SD) and CMHRs were mixed at three different mixing
      ratios, 5:5:1, 2:2:1 and 1:1:1 on dry weight basis. Lime at 2.25% was added to
      the composting mix to buffer the pH during the composting. A control without lime
      addition was also included. The mixtures were composted in 20-L in-vessel
      composters for 56 days. A maximum of 67.2% organic decomposition was achieved
      with 1:1:1 mixing ratio within 8 weeks. The seed germination index was 157.2% in
      1:1:1 mixing ratio, while other ratios showed <130.0% and the treatment without
      lime showed 40.3%. Therefore use of CMHRs as the bulking agent to compost food
      waste at the dry weight ratio of 1:1:1 (FW: SD: CMHRs) was recommended for FW
      CMHRs composting.

PMID- 29040854
TI  - Simultaneously separation of xylo-oligosaccharide and lignosulfonate from wheat
      straw magnesium bisulfite pretreatment spent liquor using ion exchange resin.
AB  - For wheat straw, an ideal bio-refinery process is that all three major components
      of biomass could be efficiently utilized to make high value chemicals, MBSP could
      directly convert the hemicelluloses and lignin into xylo-oligosaccharides and
      lignosulfonate. However, these value-added compounds still present in spent
      liquor and thus should be isolated as an individual product. In present work, a
      simple and efficient ion exchange process was developed for separating xylo
      oligosaccharides and lignosulfonate simultaneously from spent liquor. D354 resin
      was selected for its high adsorption capacity of magnesium lignosulfonate and
      remarkable selectivity. 93.09% of XOS and 98.03% of lignosulfonate were recovered
      from the treated spent liquor in a fixed bed column with D354 resin. Overall, 1 L
      of MBSP spent liquor could coproduce 9.5 g XOS and 74 g lignosulfonate. These
      results offer an opportunity for complete and effective utilization of biomass by
      a novel integrated process coupling of MBSP and ion-exchange process.

PMID- 29040855
TI  - Technoeconomic analysis of biojet fuel production from camelina at commercial
      scale: Case of Canadian Prairies.
AB  - This study undertakes technoeconomic analysis of commercial production of hydro
      processed renewable jet (HRJ) fuel from camelina oil in the Canadian Prairies. An
      engineering economic model designed in SuperPro Designer(r) investigated capital
      investment, scale, and profitability of producing HRJ and co-products (biodiesel,
      naphtha, LPG, and propane) based on biorefinery plant sizes of 112.5-675 million
      L annum-1. Under base case scenario, the minimum selling price (MSP) of HRJ was
      $1.06 L-1 for a biorefinery plant with size of 225 million L. However, it could
      range from $0.40 to $1.71 L-1 given variations in plant capacity, feedstock cost,
      and co-product credits. MSP is highly sensitive to camelina feedstock cost and co
      product credits, with little sensitivity to capital cost, discount rate, plant
      capacity, and hydrogen cost. Marginal and average cost curves suggest the region
      could support an HRJ plant capacity of up to 675 million L annum-1 (capital
      investment of $167 million).

PMID- 29040856
TI  - A novel bio-electrochemical system with sand/activated carbon separator, Al anode
      and bio-anode integrated micro-electrolysis/electro-flocculation cost effectively
      treated high load wastewater with energy recovery.
AB  - A novel bio-electrochemical system (BES) was developed by integrating micro
      electrolysis/electro-flocculation from attaching a sacrificing Al anode to the
      bio-anode, it effectively treated high load wastewater with energy recovery
      (maximum power density of 365.1 mW/m3 and a maximum cell voltage of 0.97 V), and
      achieving high removals of COD (>99.4%), NH4+-N (>98.7%) and TP (>98.6%). The
      anode chamber contains microbes, activated carbon (AC)/graphite granules and Al
      anode. It was separated from the cathode chamber containing bifunctional
      catalytic and filtration membrane cathode (loaded with Fe/Mn/C/F/O catalyst) by a
      multi-medium chamber (MMC) filled with manganese sand and activated carbon
      granules, which replaced expensive PEM and reduced cost. An air contact oxidation
      bed for aeration was still adopted before liquid entering the cathode chamber.
      micro-electrolysis/electro-flocculation helps in achieving high removal
      efficiencies and contributes to membrane fouling migration. The increase of
      activated carbon in the separator MMC increased power generation and reduced
      system electric resistance.

PMID- 29040857
TI  - Synergistic effects of anaerobic co-digestion of whey, manure and fish ensilage.
AB  - Biogas production potential of the three feedstocks fish ensilage, manure and
      whey was evaluated using biochemical methane potential (BMP) tests. Since
      anaerobic digestion of single substrates may be inefficient due to imbalances in
      the carbon-nitrogen ratio, degree of biodegradability and/or due to lack of
      nutrients needed by the microbial community, co-digestion of these substrates was
      also assessed, revealing synergistic effects and a particularly good effect of
      combining manure with fish ensilage. In this latter case, methane yields were up
      to 84% higher than the weighted average of the methane yields obtained with the
      individual substrates. The type of substrate was the dominating cause of
      variation in methane production rates and yields.

PMID- 29040858
TI  - Pyrolysis of oil palm mesocarp fiber catalyzed with steel slag-derived zeolite
      for bio-oil production.
AB  - The pyrolysis of oil palm mesocarp fiber (OPMF) was catalyzed with a steel slag
      derived zeolite (FAU-SL) in a slow-heating fixed-bed reactor at 450  degrees C,
      550  degrees C, and 600  degrees C. The catalytic pyrolysis of OPMF produced a
      maximum yield of 47 wt% bio-oil at 550  degrees C, and the crude pyrolysis vapor
      (CPV) of this process yielded crude pyrolysis oil with broad distribution of
      bulky oxygenated organic compounds. The bio-oil composition produced at 550 
      degrees C contained mainly light and stable acid-rich carbonyls at a relative
      abundance of 48.02% peak area and phenolic compounds at 12.03% peak area. The FAU
      SL high mesoporosity and strong surface acidity caused the conversion of the
      bulky CPV molecules into mostly light acid-rich carbonyls and aromatics through
      secondary reactions. The secondary reactions mechanisms facilitated by FAU-SL
      reduced the distribution of the organic compounds in the bio-oil to mostly acid
      rich carbonyls and aromatic in contrast to other common zeolite.

PMID- 29040859
TI  - The FKS family genes cause changes in cell wall morphology resulted in regulation
      of anti-autolytic ability in Saccharomyces cerevisiae.
AB  - The aim of this study was to discuss the functions of FKS family genes which
      encode beta-1, 3-glucan synthase regarding the viability and autolysis of yeast
      strain. Loss of FKS1 gene severely influences the viability and anti-autolytic
      ability of yeast. Mutation of FKS1 and FKS2 genes led to cell reconstruction,
      resulting in a sharp shrinkage of cell volume and decreased stress resistance,
      viability, and anti-autolytic ability. Deletion of FKS3 gene did not clearly
      influence the synthesis of beta-1, 3-glucan of yeast but increased the strain's
      stress resistance, viability, and anti-autolytic ability. It is suggested that
      FKS3 would be the potential target for improving the stress resistance of yeast.
      The results revealed the relationship among FKS family genes and demonstrated
      their functions on yeast cell wall construction and anti-autolytic ability.

PMID- 29040860
TI  - Organics removal, nitrogen removal and N2O emission in subsurface wastewater
      infiltration systems amended with/without biochar and sludge.
AB  - Organics removal, nitrogen removal, N2O emission and nitrogen removal functional
      gene abundances in four subsurface wastewater infiltration systems (SWISs), named
      SWIS A (no intermittent aeration without biochar and sludge), SWIS B (no
      intermittent aeration with biochar and sludge), SWIS C (intermittent aeration
      without biochar and sludge), SWIS D (intermittent aeration with biochar and
      sludge) were investigated. Intermittent aeration enhanced chemical oxygen demand
      (COD), ammonia nitrogen (NH4+-N), total nitrogen (TN) removal and the abundances
      of nitrogen removal functional genes (amoA, nxrA, napA, narG, nirS, nirK, qnorB
      and nosZ) compared to non-aerated SWISs. High COD (95.4 +/- 0.2%), NH4+-N (96.2
      +/- 0.6%), TN (86.4 +/- 0.5%) removal efficiencies and low N2O emission rate
      (18.4 mg/(m2 d)) were obtained simultaneously in intermittent aerated SWIS
      amended with biochar and sludge. The results suggested that intermittent aerated
      SWISs amended with biochar and sludge could be an effective and appropriate
      method for improving treatment performance and reducing N2O emission.

PMID- 29040861
TI  - Biomimetic aquaporin membranes for osmotic membrane bioreactors: Membrane
      performance and contaminant removal.
AB  - In this study, we investigated the performance of an osmotic membrane bioreactor
      (OMBR) enabled by a novel biomimetic aquaporin forward osmosis (FO) membrane.
      Membrane performance and removal of 30 trace organic contaminants (TrOCs) were
      examined. Results show that the aquaporin FO membrane had better transport
      properties in comparison with conventional cellulose triacetate and polyamide
      thin-film composite FO membranes. In particular, the aquaporin FO membrane
      exhibited much lower salt permeability and thus smaller reverse salt flux,
      resulting in a less severe salinity build-up in the bioreactor during OMBR
      operation. During OMBR operation, the aquaporin FO membrane well complemented
      biological treatment for stable and excellent contaminant removal. All 30 TrOCs
      selected here were removed by over 85% regardless of their diverse properties.
      Such high and stable contaminant removal over OMBR operation also indicates the
      stability and compatibility of the aquaporin FO membrane in combination with
      activated sludge treatment.

PMID- 29040862
TI  - Fast microwave-assisted ex-catalytic co-pyrolysis of bamboo and polypropylene for
      bio-oil production.
AB  - The ex-catalytic co-pyrolysis of bamboo and polypropylene (PP) with HZSM-5 was
      investigated with microwave assistance. The influences of catalytic temperature,
      feedstock/catalyst ratio, and bamboo/PP ratio on the product yields and chemical
      components of bio-oil from the co-pyrolysis were studied. When the catalytic
      temperature, feedstock/catalyst ratio, and bamboo/PP ratio were 250  degrees C,
      1:2, and 2:1, respectively, the bio-oil yield reached its maximum value at 61.62
      wt%. The oxygenate proportion compounds decreased with increasing catalyst
      content. The PP addition improved the proportions of aromatics and naphthenic
      hydrocarbons. The bio-oil was upgraded significantly from the jet fuel
      perspective. A synergistic effect also existed between bamboo and PP.

PMID- 29040863
TI  - High tolerance of and removal of cefazolin sodium in single-chamber microbial
      fuel cells operation.
AB  - Single-chamber microbial fuel cells (MFCs) have been shown to be a promising
      approach for cefazolin sodium (CFZS)-contaminated wastewater treatment, in terms
      of electricity production, high CFZS tolerance and effective CFZS removal. MFCs
      exposed to CFZS loadings up to 100 mg L-1, produced stable power of 18.2 +/- 1.1
      W m-3 and a maximum power of 30.4 +/- 2.1 W m-3, similar to that of CFZS-free
      MFCs (stable power 19.4 +/- 0.8 W m-3 and maximum power 32.5 +/- 1.6 W m-3),
      notwithstanding a longer acclimitisation MFC activation. More anodophilic genera
      (i.e. Acinetobacter, Stenotrophomonas, Lysinibacillus) and antibiotic-resisting
      genera (i.e. Dysgonomonas) were enriched in CFZS acclimitised anodes. Both the
      thickness of biofilms and the duration of CFZS acclimitisation were essential for
      the development of high CFZS tolerance (e.g. 450 mg L-1). The inhibition of MFCs
      by CFZS was reversible. The present MFCs generated a CFZS removal rate of 1.2-6.8
      mg L-1 h-1 without any apparent inhibition of electricity production.

PMID- 29040864
TI  - Enhanced enzymatic hydrolysis by adding long-chain fatty alcohols using film as a
      structure model.
AB  - Many positive effects of additives on enzymatic hydrolysis of lignocellulosic
      materials have been investigated, but limited information has been reported on
      the use of long-chain fatty alcohols (LFAs) for enzymatic hydrolysis by biospired
      models. In this study, effects of LFAs on enzymatic hydrolysis were evaluated
      using biomimetic film asa structure model. LFAs clearly improved the
      digestibility of cellulose film from 65.1% to 77.9%, which was higher than that
      the digestibility of lignin-cellulose film from 53.9% to 66.2%. Further study
      indicated that the promotion ascribed to the effect of LFAs, which might provide
      more active points of chemical reaction and keep the stability of cellulase.
      Moreover, the digestibility of lignin-cellulose film increased by 12.3%, which
      might because the denaturation and nonproductive adsorption of cellulase were
      well prevented by supplementation of LFAs. An efficient strategy was developed to
      improve the enzymatic hydrolysis efficiency in the study of lignocellulosic
      bioconversion.

PMID- 29040865
TI  - Do microbial communities in an anaerobic bioreactor change with continuous
      feeding sludge into a full-scale anaerobic digestion system?
AB  - Microbial communities of sludge samples from a full-scale anaerobic digestion
      (AD) fed with primary sludge (PS) and excess sludge (ES) were analyzed using qPCR
      and MiSeq. The results showed that the microbial composition of digested sludge
      remained relatively stable but was partially changed by microbial immigration
      from feeding sludge. The dominant archaea in the digested sludge were largely the
      same as those in the feeding sludge, but their abundances differed markedly. The
      dominant fungal genera in the digested sludge were different from those in PS but
      were similar to those in ES. Various differences in bacterial community
      differences between digested sludge and PS/ES were observed. Notably, this study
      is the first to suggest Verrucomicrobia is the predominant bacterial phylum in
      the digested sludge, and that numerous unreported microorganisms belonging to the
      order LD1-PB3 existed in this AD system and potentially played roles in the
      processes of hydrolysis, fermentation, and acetogenesis.

PMID- 29040866
TI  - Carbon-dependent alleviation of ammonia toxicity for algae cultivation and
      associated mechanisms exploration.
AB  - Ammonia toxicity in wastewater is one of the factors that limit the application
      of algae technology in wastewater treatment. This work explored the correlation
      between carbon sources and ammonia assimilation and applied a glucose-assisted
      nitrogen starvation method to alleviate ammonia toxicity. In this study, ammonia
      toxicity to Chlorella sp. was observed when NH3-N concentration reached 28.03mM
      in artificial wastewater. Addition of alpha-ketoglutarate in wastewater promoted
      ammonia assimilation, but low utilization efficiency and high cost of alpha
      ketoglutarate limits its application in wastewater treatment. Comparison of three
      common carbon sources, glucose, citric acid, and sodium bicarbonate, indicates
      that in terms of ammonia assimilation, glucose is the best carbon source.
      Experimental results suggest that organic carbon with good ability of generating
      energy and hydride donor may be critical to ammonia assimilation. Nitrogen
      starvation treatment assisted by glucose increased ammonia removal efficiencies
      and algal viabilities.

PMID- 29040867
TI  - Long-term follow-up of anterior thalamic deep brain stimulation in epilepsy: A 11
      year, single center experience.
AB  - PURPOSE: Anterior thalamic deep brain stimulation (ATN DBS) is an emerging,
      effective treatment for patients with drug-resistant epilepsy, but long-term
      results on its efficacy and safety are lacking. To evaluate the long-term
      efficacy and safety of ATN DBS treatment, as well as predictors of its success,
      in patients with drug-refractory epilepsy (DRE). METHOD: We retrospectively
      studied clinical outcomes in 29 consecutive refractory epilepsy patients treated
      by a single DBS team (two neurosurgeons, four neurologists) over an 11-year
      period, for whom follow-up was performed for up to 137 months (mean, 74.9
      months). RESULTS: The average participant was 30.7 (+/-10.4) years old and had
      epilepsy for 19.3 (+/-9.0) years. The mean preoperative frequency of disabling
      partial or generalized tonic-clonic seizures was 27.5 (+/-8.6, SE) seizures a
      month. The median percent seizure reduction was 71.3% at 1year, 73.9% at 2 years,
      and ranged from 61.8% to 80.0% over post-implant years 3 through 11 in the long
      term study (overall 70% median reduction). In the 11-year study period, 13.8%
      (4/29) of subjects were seizure-free for at least 12 months during this time.
      There was only one symptomatic intracranial hemorrhage that happened during
      follow-up (3.4%). Infection requiring removal and later re-implantation of
      hardware occurred in only 1 of 30 patients (3.3%), who was subsequently excluded
      from our follow-up assessment. Hardware malfunction including lead disconnection
      occurred in 2 of 29 cases (6.9%). Revision of lead position to redeem poor
      clinical response was performed in 3 of 58 implanted leads (5.2%). CONCLUSIONS:
      ATN DBS can be an effective therapy in a variety of patients with DRE.
      Importantly, we provide evidence that significant therapeutic efficacy can be
      sustained for up to 11 years. Neurological complications were rather rare, but
      long-term hardware-related complications should be followed arrectis auribus.

PMID- 29040869
TI  - Accessing the long-time limit in diffusion NMR: The case of singlet assisted
      diffusive diffraction q-space.
AB  - The latest developments in the field of long-lived spin states are merged with
      pulsed-field gradient techniques to extend the diffusion time beyond what is
      currently achievable in standard q-space diffusive-diffraction studies. The
      method uses nearly-equivalent spin-1/2 pairs that let diffusion times of the
      order of many minutes to be measured allowing access to the long-time limit in
      cavities of macroscopic size (millimeters). A pulse sequence suitable to exploit
      this regime has been developed and validated with the use of numerical
      simulations and experiments.

PMID- 29040868
TI  - Identification of a novel proinsulin-associated SNP and demonstration that
      proinsulin is unlikely to be a causal factor in subclinical vascular remodelling
      using Mendelian randomisation.
AB  - BACKGROUND AND AIMS: Increased proinsulin relative to insulin levels have been
      associated with subclinical atherosclerosis (measured by carotid intima-media
      thickness (cIMT)) and are predictive of future cardiovascular disease (CVD),
      independently of established risk factors. The mechanisms linking proinsulin to
      atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified
      nine loci associated with circulating proinsulin levels. Using proinsulin
      associated SNPs, we set out to use a Mendelian randomisation approach to test the
      hypothesis that proinsulin plays a causal role in subclinical vascular
      remodelling. METHODS: We studied the high CVD-risk IMPROVE cohort (n = 3345),
      which has detailed biochemical phenotyping and repeated, state-of-the-art, high
      resolution carotid ultrasound examinations. Genotyping was performed using
      Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin
      associated loci. Participants with type 2 diabetes (n = 904) were omitted from
      the analysis. Linear regression was used to identify proinsulin-associated
      genetic variants. RESULTS: We identified a proinsulin locus on chromosome 15
      (rs8029765) and replicated it in data from 20,003 additional individuals. An 11
      SNP score, including the previously identified and the chromosome 15 proinsulin
      associated loci, was significantly and negatively associated with baseline
      IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression
      measures. However, MR-Eggers refuted any significant effect of the proinsulin
      associated 11-SNP score, and a non-pleiotropic SNP score of three variants
      (including rs8029765) demonstrated no effect on baseline or progression cIMT
      measures. CONCLUSIONS: We identified a novel proinsulin-associated locus and
      demonstrated that whilst proinsulin levels are associated with cIMT measures,
      proinsulin per se is unlikely to have a causative effect on cIMT.

PMID- 29040870
TI  - Parkin absence accelerates microtubule aging in dopaminergic neurons.
AB  - Loss-of-function caused by mutations in the parkin gene (PARK2) lead to early
      onset familial Parkinson's disease. Recently, mechanistic studies proved the
      ability of parkin in regulating mitochondria homeostasis and microtubule (MT)
      stability. Looking at these systems during aging of PARK2 knockout mice, we found
      that loss of parkin induced an accelerated (over)acetylation of MT system both in
      dopaminergic neuron cell bodies and fibers, localized in the substantia nigra and
      corpus striatum, respectively. Interestingly, in PARK2 knockout mice, changes of
      MT stability preceded the alteration of mitochondria transport. Moreover, in-cell
      experiments confirmed that loss of parkin affects mitochondria mobility and
      showed that this defect depends on MT system as it is rescued by paclitaxel, a
      well-known MT-targeted agent. Furthermore, both in PC12 neuronal cells and in
      patients' induced pluripotent stem cell-derived midbrain neurons, we observed
      that parkin deficiencies cause the fragmentation of stable MTs. Therefore, we
      suggest that parkin acts as a regulator of MT system during neuronal aging, and
      we endorse the hypothesis that MT dysfunction may be crucial in the pathogenesis
      of Parkinson's disease.

PMID- 29040871
TI  - Gray matter networks and clinical progression in subjects with predementia
      Alzheimer's disease.
AB  - We studied whether gray matter network parameters are associated with rate of
      clinical progression in nondemented subjects who have abnormal amyloid markers in
      the cerebrospinal fluid (CSF), that is, predementia Alzheimer's disease.
      Nondemented subjects (62 with subjective cognitive decline; 160 with mild
      cognitive impairment (MCI); age = 68 +/- 8 years; Mini-Mental State Examination
      (MMSE) = 28 +/- 2.4) were selected from the Amsterdam Dementia Cohort when they
      had abnormal amyloid in CSF (<640 pg/mL). Networks were extracted from gray
      matter structural magnetic resonance imaging (MRI), and 9 parameters were
      calculated. Cox proportional hazards models were used to test associations
      between each connectivity predictor and rate of progression to MCI or dementia.
      After a median time of 2.2 years, 122 (55%) subjects showed clinical progression.
      Lower network parameter values were associated with increased risk for
      progression, with the strongest hazard ratio of 0.29 for clustering (95%
      confidence interval = 0.12-0.70; p < 0.01). Results remained after correcting for
      tau, hippocampal volume, and MMSE scores. Our results suggest that at predementia
      stages, gray matter network parameters may have use to identify subjects who will
      show fast clinical progression.

PMID- 29040872
TI  - Highly elevated plasma level of von Willebrand factor accelerates the formation
      of platelet thrombus under high shear stress in plasma with deficient ADAMTS13
      activity.
AB  - Upshaw-Schulman syndrome (USS) is a thrombo-hemorrhagic disease caused by
      congenital deficiency of ADAMTS13 due to ADAMTS13 gene mutations. USS is
      characterized by repeated episodes of thrombocytopenia and microangiopathic
      hemolytic anemia that respond dramatically to infusions of fresh frozen plasma.
      There are two phenotypic expressions of USS: one is the early-onset type and the
      other, the late-onset type, is asymptomatic during childhood with the first bout
      of thrombotic thrombocytopenic purpura (TTP) developing after adolescence or
      during adulthood. We found that gravida with the latter phenotype developed
      thrombocytopenia and hemolytic anemia during the second or third trimesters,
      often followed by thrombotic microangiopathies (TMAs). These phenomena suggest
      that elevated plasma von Willebrand Factor (VWF) might be crucial because plasma
      levels of VWF antigen usually increase by 200-500% during this period of
      gestation. Here, we performed platelet function assays using a mixture of anti
      coagulated blood from normal volunteers, human VWF, anti-ADAMTS13 monoclonal
      antibody A10, and purified plasma-derived ADAMTS13 to investigate the effect of
      plasma VWF levels on platelet thrombus formation in the context of deficient
      ADAMTS13. In vitro studies showed that mural thrombus formation and platelet
      aggregation under high shear stress were markedly augmented by increasing the
      amounts of exogenously added VWF when ADAMTS13 activity was deficient, as may be
      the case in the in vivo circulation of gravida with USS. These results suggest
      that highly elevated plasma VWF might accelerate platelet thrombus formation not
      only in the circulation but also on the surface of vascular endothelial cells in
      the setting of ADAMTS13 deficiency in USS.

PMID- 29040873
TI  - Hazard perception skills of young drivers with Attention Deficit Hyperactivity
      Disorder (ADHD) can be improved with computer based driver training: An
      exploratory randomised controlled trial.
AB  - BACKGROUND: Young drivers with Attention Deficit Hyperactivity Disorder (ADHD)
      are at higher risk of road traffic injuries than their peers. Increased risk
      correlates with poor hazard perception skill. Few studies have investigated
      hazard perception training using computer technology with this group of drivers.
      OBJECTIVES: *Determine the presence and magnitude of the between-group and within
      subject change in hazard perception skills in young drivers with ADHD who
      receive Drive Smart training. *Determine whether training-facilitated change in
      hazard perception is maintained over time. METHODS: This was a feasibility study,
      randomised control trial conducted in Australia. The design included a delayed
      treatment for the control group. Twenty-five drivers with a diagnosis of ADHD
      were randomised to the Immediate Intervention or Delayed Intervention group.The
      Immediate Intervention group received a training session using a computer
      application entitled Drive Smart. The Delayed Intervention group watched a
      documentary video initially (control condition), followed by the Drive Smart
      computer training session. The participant's hazard perception skill was measured
      using the Hazard Perception Test (HPT). FINDINGS: After adjusting for baseline
      scores, there was a significant betweengroup difference in post-intervention HPT
      change scores in favour of the Immediate Intervention group. The magnitude of the
      effect was large. There was no significant within-group delayed intervention
      effect. A significant maintenance effect was found at 6-week follow-up for the
      Immediate Intervention group. CONCLUSIONS: The hazard perception skills of
      participants improved following training with large effect size and some
      maintenance of gain. A multimodal approach to training is indicated to facilitate
      maintenance. A full-scale trial is feasible.

PMID- 29040874
TI  - Surface functionalized exosomes as targeted drug delivery vehicles for cerebral
      ischemia therapy.
AB  - The safe and effective delivery of drugs is a major obstacle in the treatment of
      ischemic stroke. Exosomes hold great promise as an endogenous drug delivery
      nanosystem for the treatment of cerebral ischemia given their unique properties,
      including low immunogenicity, innate stability, high delivery efficiency, and
      ability to cross the blood-brain barrier (BBB). However, exosome insufficient
      targeting capability limits their clinical applications. In this study, the
      c(RGDyK) peptide has been conjugated to the exosome surface by an easy, rapid,
      and bio-orthogonal chemistry. In the transient middle cerebral artery occlusion
      (MCAO) mice model, The engineered c(RGDyK)-conjugated exosomes (cRGD-Exo) target
      the lesion region of the ischemic brain after intravenous administration.
      Furthermore, curcumin has been loaded onto the cRGD-Exo, and administration of
      these exosomes has resulted in a strong suppression of the inflammatory response
      and cellular apoptosis in the lesion region. The results suggest a targeting
      delivery vehicle for ischemic brain based on exosomes and provide a strategy for
      the rapid and large-scale production of functionalized exosomes.

PMID- 29040875
TI  - Biomechanical regulation of drug sensitivity in an engineered model of human
      tumor.
AB  - Predictive testing of anticancer drugs remains a challenge. Bioengineered
      systems, designed to mimic key aspects of the human tumor microenvironment, are
      now improving our understanding of cancer biology and facilitating clinical
      translation. We show that mechanical signals have major effects on cancer drug
      sensitivity, using a bioengineered model of human bone sarcoma. Ewing sarcoma
      (ES) cells were studied within a three-dimensional (3D) matrix in a bioreactor
      providing mechanical loadings. Mimicking bone-like mechanical signals within the
      3D model, we rescued the ERK1/2-RUNX2 signaling pathways leading to drug
      resistance. By culturing patient-derived tumor cells in the model, we confirmed
      the effects of mechanical signals on cancer cell survival and drug sensitivity.
      Analyzing human microarray datasets, we showed that RUNX2 expression is linked to
      poor survival in ES patients. Mechanical loadings that activated signal
      transduction pathways promoted drug resistance, stressing the importance of
      introducing mechanobiological cues into preclinical tumor models for drug
      screening.

PMID- 29040876
TI  - Species-specific control of hepatocyte growth factor expression and production in
      adipocytes in a differentiation-dependent manner.
AB  - Hepatocyte growth factor (HGF) is a mesenchymal cell-derived factor that
      regulates cell growth, cell motility, and morphogenesis. Since there are
      conflicting reports on HGF-producing cells, we herein examined HGF activity in
      conditioned medium (CM) of bovine and mouse preadipocytes before and after
      adipogenic differentiation. CM of bovine adipocytes and mouse preadipocytes
      induced the morphogenesis of mammary epithelial cells that was inhibited by an
      NK4 HGF antagonist, whereas CM of bovine preadipocytes and mouse adipocytes did
      not. HGF mRNA expression was increased by a treatment with dexamethasone and
      isobutylmethylxanthine in bovine as well as human cells, whereas it was decreased
      in rodent cells. It was unfortunate that HGF gene promoter activity failed to
      reflect HGF mRNA expression in these cells. After actinomycin D treatment,
      expression of HGF mRNA remained stable in pre- and differentiated bovine
      adipocytes and mouse preadipocytes, whereas rapidly decreased in mouse
      differentiated adipocytes. These results indicate that expression and production
      of HGF are regulated in a species-specific adipogenic differentiation-dependent
      manner and suggest that the decrease in HGF mRNA in mouse differentiated
      adipocytes is, at least in part, mediated by differentiation-dependent loss of
      its stability.

PMID- 29040877
TI  - Corpus luteum dynamics after ovulation induction with or without previous
      exposure to progesterone in prepubertal Nellore heifers.
AB  - The objectives of this study were 1) to monitor corpus luteum (CL) dynamics after
      two different protocols of ovulation induction in prepubertal Nellore heifers,
      and 2) to determine differences in luteal function. Fifty-seven heifers (weight
      289.61 +/- 32.28 kg, BCS 5.66 +/- 0.65, age 17.47 +/- 0.81 months) were divided
      into two groups: GP4+GnRH received a progesterone (P4) device of 3rd use for 10
      days, followed by the administration of 0.02 mg buserelin acetate (GnRH) 48 h
      after removal of the device, and GGnRH received only GnRH. The CLs formed were
      monitored by ultrasonography every 2 days until their functional regression
      (decrease in the color Doppler signal and serum P4 concentration < 1 ng/mL),
      determining their diameter and area, numerical pixel value (NPV), pixel
      heterogeneity, and vascularization percentage. The peak systolic velocity, end
      diastolic velocity, resistivity index and pulsatility index (PI) of the ovarian
      artery and serum P4 concentration were also measured. A lifespan of the CL of
      more than 16 days was classified as normal-function and of less than 16 days as
      premature regression. The variables were compared between treatments, CL
      categories (normal-functional, prematurely regressed or non-functional), days of
      evaluation, and their interactions using the MIXED procedure of the SAS program
      (p <= 0.05). Three animals of each group (6/57 = 11%) did not respond to
      treatment, corresponding to an ovulation rate of 89%. There was a higher
      percentage of normal-function CLs in GP4+GnRH (81%) and a higher percentage of
      non-functional CLs in GGnRH (52%; P4 concentration < 1 ng/mL in all assessments).
      Normal-function CLs exhibited a greater area, vascularization percentage and P4
      concentration than prematurely regressed and non-functional CLs. Lower diameter,
      area, NPV and P4 concentration were observed for non-functional CLs, but there
      was no difference in vascularization percentage compared to prematurely regressed
      CLs. Progesterone concentration was efficient in diagnosing CL function and was
      positively correlated with CL area (r = 0.62; p < 0.001) and vascularization
      percentage (r = 0.38; p < 0.001). Diameter and PI were important for the early
      diagnosis of non-functional and prematurely regressed CLs, respectively. In
      conclusion, luteal function differed for the first CL that develops after
      ovulation induction in prepubertal heifers. Ultrasonographic parameters
      (diameter, area, NPV, vascularization percentage, and PI) can be used to predict
      CL function.

PMID- 29040878
TI  - C-Phycocyanin supplementation during in vitro maturation enhances pre
      implantation developmental competence of parthenogenetic and cloned embryos in
      pigs.
AB  - C-Phycocyanin (C-PC), a protein from green microalgae, has been suggested to
      possess various biological activities, including antioxidant and free radical
      scavenging properties. The aim of the current study was to explore the effects of
      C-PC on the maturation of porcine oocytes and subsequent developmental competence
      after parthenogenetic activation and somatic cell nuclear transfer (SCNT) as well
      as the underlying mechanisms. There was no significant improvement in nuclear
      maturation rates between the control and C-PC supplementation groups (1, 3, 5, 10
      MUg/mL). However, supplementation of 5 MUg/mL C-PC in the maturation medium
      significantly increased blastocyst formation and hatching rates after
      parthenogenetic activation (59.6 +/- 3.6% and 33.0 +/- 2.6% vs. 49.8 +/- 3.5% and
      27.4 +/- 2.4%, respectively). In addition, the presence of C-PC during the
      maturation period significantly improved blastocyst formation rates and total
      cell numbers after SCNT (24.8 +/- 1.9% and 42.2 +/- 3.3 vs. 21.6 +/- 2.2% and
      39.5 +/- 3.4, respectively) compared to the control group. Furthermore, cellular
      proliferation and the expression of pluripotency-related genes (SOX2 and NANOG)
      were increased in cloned blastocysts derived from the C-PC supplemented group.
      Importantly, C-PC supplementation during maturation not only improved cumulus
      expansion and increased the expression of cumulus expansion-related genes (HAS2,
      PTX3, and PTGS2), but also enhanced antioxidant capacity, improved mitochondria
      function, and decreased cathepsin B activity in porcine oocytes. These results
      demonstrate that C-PC may be useful for improving porcine oocyte quality and
      subsequent developmental competence in embryos.

PMID- 29040879
TI  - Influence of sexual behavior of Dorper rams treated with glutamate and/or
      testosterone on reproductive performance of anovulatory ewes.
AB  - The aim of this study was to determine if exogenous administration of glutamate
      and (or) testosterone to male rams during the season of reproductive arrest is
      able to re-activate male sexual behavior and, later on, to promote through the
      male effect, both sexual and reproductive competence of anovulatory nulliparous
      ewes. Therefore, an experiment was performed under long-day photoperiods (spring;
      photo-reproductive arrest, 26 degrees N). Dorper rams were randomly divided into
      four homogeneous experimental groups (n = 5 males each) regarding live weight
      (LW), body condition score (BCS), scrotal circumference (SC) and odor intensity
      (OI). Then, groups were treated with: i) GG (7 mg kg-1 LW of glutamate, every 4d
      * 30d, im.), ii) GGT (7 mg kg-1 LW of glutamate every 4d * 30d im + 25 mg of
      testosterone propionate, every 3d * 15d, im.), iii) GT (25 mg of testosterone
      propionate every 3d * 15d, im, and iv) GC (1 mL of saline, every 4d * 30d, im.).
      Thereafter, Dorper rams, (n = 4 per group) were selected and exposed to Dorper
      anovulatory-nulliparous ewes divided in four groups (n = 14 ewes each), and all
      the appetitive (ASB) and consummatory (CSB) sexual behaviors and indicators of
      sexual rest (ISR) were registered during the first 48 h of this male-to-females
      contact. Thereafter, males continued the male-to-female contact for another 8 d,
      in order to quantify the ewe's sexual and reproductive response through the male
      effect. During the sexual behavior tests, the GGT rams showed the highest ASB +
      CSB frequencies (P < 0.05) followed by the GG-rams with the lowest frequencies
      showed by the GC and GT groups. While the highest ISR behaviors were shown by the
      GG and GGT groups (P < 0.05) followed by the GC and GT-rams, no differences
      occurred regarding LW, BCS, and SC along the experimental breeding, with the
      largest (P < 0.05) OI shown by the GGT-rams and the lowest value observed in the
      control rams. Regarding the reproductive response of the nulliparous-anovulatory
      ewes exposed to treated rams, the glutamate + testosterone treated males induced
      not only an increased (P < 0.05) ovulatory activity and faster (P < 0.05) estrus
      response but an augmented (P < 0.05) pregnancy rate of the previously anovulatory
      ewes. To conclude, whereas the GG and GGT treatments generated encouraging sexual
      and reproductive outcomes, our results are also thought-provoking from a
      comparative sexual behavior perspective while may embrace potential applications
      to other animal industries.

PMID- 29040880
TI  - Prolonged parturition and impaired placenta expulsion increase the risk of
      postpartum metritis and delay uterine involution in sows.
AB  - It was hypothesized that prolonged parturition and impaired placenta expulsion
      increase the risk of postpartum metritis and delay uterine involution. At
      parturition, for 99 Yorkshire x Large White sows (parity 2-5), we determined the
      number of liveborn (NLP; 14.8 +/- 3.4) and stillborn piglets (NSP; 1.1 +/- 1.1),
      farrowing duration (FAR, time between first and last piglet; 333 +/- 249 min),
      placenta expulsion duration (PLA, time between first and last placental part; 292
      +/- 241 min) and number of expelled placental parts (PART; 3.0 +/- 1.0). FAR was
      categorized as 'normal' (<300 min; n = 44/99) or 'prolonged' (>300 min; n =
      55/99). The relative PLA (rPLA; (PLA * 100)/FAR; 76 +/- 101%) and the relative
      PART (rPART; (PART * 100)/(NLP + NSP); 22 +/- 8%) were calculated and placenta
      expulsion was categorized as 'normal' (rPLA and rPART > 10%; n = 93/99) or
      'impaired' (relPLA and relPART < 10%; n = 6/99). We also recorded whether manual
      palpation occurred (Yes/No) and/or oxytocin was used (Yes/No). After parturition,
      an ultrasound examination of the uterus was performed once for each sow between
      the 2nd and 7th day postpartum and the uterine size (mean sectional area of three
      to five uterine cross-sections) and intrauterine fluid accumulation (Yes/No) were
      recorded. Uterine size was categorized as 'normal' (n = 55/99) or 'enlarged' (n =
      44/99) and used as an indicator of delayed uterine involution. Intrauterine fluid
      was used as an indicator of metritis. Prolonged FAR (35/54, 2.0 +/- 0.5, 13.1,
      7.6; n/N, beta +/- SE, Wald chi2, Odds; P = 0.001), manual palpation (12/17, 1.5
      +/- 0.7, 4.4, 4.3; P = 0.036), oxytocin administration (18/31, - 1.5 +/- 0.7,
      4.7, 0.2, P = 0.040) and NSP >= 2 (15/21, 1.4 +/- 0.7, 3.8, 3.9; P = 0.052) were
      associated with increased uterine size (n = 44/99) and NSP >= 2 (7/21, 2.6 +/-
      0.9, 8.7, 13.7; P = 0.003), manual palpation (10/17, 1.8 +/- 0.8, 5.0, 6.0; P =
      0.025), prolonged FAR (13/15, 1.7 +/- 0.8, 4.3, 5.7; P = 0.039) and impaired PLA
      (4/6, 3.3 +/- 1.7, 4.0, 26.9; P = 0.044) with intrauterine fluid accumulation (n
      = 15/99). The results confirm the hypothesis, indicating that prolonged
      parturition and impaired placenta expulsion increased the risk for postpartum
      metritis. Stillborn piglets and manual palpation were also identified as risk
      factors. Postpartum metritis delays uterine involution whereas the use of
      exogenous oxytocin supports it.

PMID- 29040881
TI  - New high-throughput measurement systems for radioactive wastes segregation and
      free release.
AB  - This paper addresses the measurement facilities for pre-selection of waste
      materials prior to measurement for repository acceptance or possible free release
      (segregation measurement system); and free release (free release measurement
      system), based on a single standardized concept characterized by unique, patented
      lead-free shielding. The key objective is to improve the throughput, accuracy,
      reliability, modularity and mobility of segregation and free-release measurement.
      This will result in a more reliable decision-making with regard to the safe
      release and disposal of radioactive wastes into the environment and, resulting in
      positive economic outcomes. The research was carried out within "Metrology for
      Decommissioning Nuclear Facilities" (MetroDecom) project.

PMID- 29040882
TI  - Separation of weighable amounts of 10Be from proton irradiated graphite.
AB  - Large amounts of 10Be are produced at the PSI muon production facility by high
      energy proton spallation in polycrystalline graphite. For the extraction of 10Be
      out of large amounts of carbon, pyrolysis followed by chemical purification has
      been performed. Approx. 270g of graphite from Target E92, which had received a
      total proton charge of 29 Ah between 2002 and 2005, have been burned at 1000
      degrees C in a stream of oxygen. The volatile radioactive oxidation product 3H2O
      was trapped in 3 water bubblers connected in series. The remainder, a white
      hygroscopic solid material mainly consisting of 7Li2O, 9/10BeO and 10/11B2O3, was
      dissolved in HF and subsequently purified by ion exchange chromatography.
      Radioactive impurities such as 22Na, 44Ti, 54Mn, 60Co, 101Rh, 133Ba and 172Hf
      have been separated from the final product. The purified material represents a
      mixture of approx. 6.5mg 9Be and 3.5mg (3.3MBq) 10Be. It is ready to be used for
      scientific investigations requiring large amounts of this precious isotope.

PMID- 29040883
TI  - Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for emergency cardiac
      support.
AB  - PURPOSE: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) may provide
      benefit to patients in refractory cardiac arrest and cardiogenic shock. We aim to
      summarize our center's 6-year experience with resuscitative VA-ECMO. MATERIALS
      AND METHODS: A retrospective medical record review (April 2009 to 2015) was
      performed on consecutive non-cardiotomy patients who were managed with VA-ECMO
      due to refractory in- or out-of-hospital cardiac (IHCA/OHCA) arrest (E-CPR) or
      refractory cardiogenic shock (E-CS) with or without preceding cardiac arrest. Our
      primary outcome was survival to hospital discharge and good neurological status
      (Cerebral Performance Category 1-2). RESULTS: There were a total of 22 patients
      who met inclusion criteria of whom 9 received E-CPR (8 IHCA, 1 OHCA) and 13
      received E-CS. The median age for E-CPR patients was 52 [IQR 45, 58] years, and
      54 [IQR 38, 64] years for E-CS patients. Cardiac arrest duration was 70.33 (SD
      39.56) min for the E-CPR patients, and 24.67 (SD 26.73) min for the 9 patients
      treated with E-CS who had previously arrested. Initial cardiac arrest rhythms
      were pulseless electrical activity (39%), ventricular fibrillation (33%), or
      ventricular tachycardia (28%). A total of 18/22 patients were successfully weaned
      from VA-ECMO (78%); 16 patients survived to hospital discharge (73%) with 15 in
      good neurological condition. CONCLUSION: The initiation of VA-ECMO at our center
      for treatment of refractory cardiac arrest and cardiogenic shock yielded a high
      proportion of survivors and favorable neurological outcomes.

PMID- 29040884
TI  - Heart rate variability feature selection in the presence of sleep apnea: An
      expert system for the characterization and detection of the disorder.
AB  - We introduce a sleep apnea characterization and classification approach based on
      a Heart Rate Variability (HRV) feature selection process, thus focusing on the
      characterization of the underlying process from a cardiac rate point of view.
      Therefore, we introduce linear and nonlinear variables, namely Cepstrum
      Coefficients (CC), Filterbanks (Fbank) and Detrended Fluctuation Analysis (DFA).
      Logistic Regression, Linear Discriminant Analysis and Quadratic Discriminant
      Analysis were used for classification purposes. The experiments were carried out
      using two databases. We achieved a per-segment accuracy of 84.76% (sensitivity =
      81.45%, specificity = 86.82%, AUC = 0.92) in the Apnea-ECG Physionet database,
      whereas in the HuGCDN2014 database, provided by the Dr. Negrin University
      Hospital (Las Palmas de Gran Canaria, Spain), the best results were: accuracy =
      81.96%, sensitivity = 70.95%, specificity = 85.47%, AUC = 0.87. The former
      results were comparable or better than those obtained by other methods for the
      same database in the recent literature. We have concluded that the selected
      features that best characterize the underlying process are common to both
      databases. This supports the fact that the conclusions reached are potentially
      generalizable. The best results were obtained when the three kinds of features
      were jointly used. Another notable fact is the small number of features needed to
      describe the phenomenon. Results suggest that the two first Fbanks, the first CC
      and the first DFA coefficient are the variables that best describe the RR pattern
      in OSA and, therefore, are especially relevant to extract discriminative
      information for apnea screening purposes.

PMID- 29040885
TI  - Bimodal decompression sickness onset times are not related to dive type or event
      severity.
AB  - Human decompression sickness (DCS) is a condition associated with
      depressurization during underwater diving. Human research dive trial data
      containing dive outcome (DCS, no-DCS) and symptom information are used to
      calibrate probabilistic DCS models. DCS symptom onset time information is
      visualized using occurrence density functions (ODF) which plot the DCS onset rate
      per unit time. For the BIG292 human dive trial data set, a primary U.S. Navy
      model calibration set, the ODFs are bimodal, however probabilistic models do not
      produce bimodal ODFs. We investigate the source of bimodality by partitioning the
      BIG292 data based on dive type, DCS event severity, DCS symptom type,
      institution, and chronology of dive trial. All but one variant of data
      partitioning resulted in a bimodal or ambiguously shaped ODF, indicating that ODF
      bimodality is not related to the dive type or the DCS event severity. Rather, we
      find that the dive trial medical surveillance protocol used to determine DCS
      symptom onset time may have biased the reported event window. Thus, attempts to
      develop probabilistic DCS models that reproduce BIG292 bimodality are unlikely to
      result in an improvement in model performance for data outside of the calibration
      set.

PMID- 29040887
TI  - Physical status and frailty index in nursing home residents: Results from the
      INCUR study.
AB  - AIM: The Short Physical Performance Battery (SPPB) is a widely used instrument
      for measuring physical performance, consisting of 3 sub-tests: a hierarchical
      test of balance, a gait speed test, and a chair stand test. Although equally
      considered in the computation of the SPPB score, each of the components may
      present a specific and different weight in clinical practice. The aim of this
      study was to estimate the relationship between SPPB and its component of an age
      related deficit accumulation index (the so-called Frailty Index [FI] proposed by
      Rockwood). METHOD: Data are from a longitudinal cohort study (ie, the Incidence
      of pNeumonia and related ConseqUences in nursing home Residents [INCUR]) of 730
      older persons (74.29% women) living in 13 French nursing homes. The FI was
      computed as the ratio between 30 actual and potential deficits the participant
      might have presented at the baseline visit (range between 0 [no deficit] and 1
      [30 deficits]). Physical status was assessed using the SPPB score at baseline.
      Descriptive statistics and linear regression analyses were used to determine the
      relationship between the SPPB and FI and estimate which components of the SPPB
      were most strongly associated with the FI. RESULTS: Mean age of participants was
      86.5 (SD 7.5) years, with a mean FI of 0.37 (SD 0.11) and SPPB of 2.5 (range
      between 0 and 12). The SPPB and its components were all significantly associated
      with the FI, but the magnitude of the associations varied. Linear regression
      analyses adjusted for age, sex, showed that the balance test [beta=-0.045 (95%CI 
      0.042; -0.028), p<0.0001] and chair stand test [beta=-0.040 (95%CI -0.054; 
      0.027), p<0.0001] was more strongly associated with the FI than the gait speed
      [beta=-0.015 (95%CI -0.021; -0.008), p<0.0001]. CONCLUSION: Of the 3 components
      of the SPPB, both balance and chair tests seem particularly relevant indicator of
      frailty among very old and complex elders living in nursing homes.

PMID- 29040886
TI  - Role of N6-methyladenosine modification in cancer.
AB  - As the most abundant internal modification in eukaryotic messenger RNAs
      identified, N6-methyladenosine (m6A) has been shown recently to play essential
      roles in various normal bioprocesses. Evidence is emerging that m6A modification
      and its regulatory proteins also play critical roles in various cancers including
      leukemia, brain tumor, breast cancer and lung cancer, etc. For instance, FTO, the
      first m6A demethylase identified, has been reported recently to play an oncogenic
      role in leukemia and glioblastoma. ALKBH5 (another m6A demethylase) has been
      reported to exert a tumor-promoting function in glioblastoma and breast cancer.
      METTL3 (a major m6A methyltransferase) likely plays distinct roles between
      glioblastoma and lung cancer. Here we discuss the recent progress and future
      prospects in study of m6A machinery in cancer.

PMID- 29040888
TI  - Physical capability predicts mortality in late mid-life as well as in old age:
      Findings from a large British cohort study.
AB  - INTRODUCTION: Low physical capability predicts mortality, perhaps by association
      with co-morbidity. However, few studies include participants <70years old with
      lower co-morbidity burdens compared to older adults. We examined relationships
      between usual walking speed (UWS), timed chair stands speed, grip strength,
      standing balance and all-cause mortality in 8477 participants aged 48-92years
      enrolled in the European Prospective Investigation of Cancer-Norfolk study.
      METHODS: Participants (55.1% female) were followed up for 6.0 years (inter
      quartile range 4.6, 7.5). Associations were examined using Cox proportional
      hazards regression by age-group (<70years versus >=70years) and then in the whole
      cohort adjusted for age, sex, anthropometry, history of
      diabetes/stroke/myocardial infarction/cancer, smoking, alcohol intake,
      socioeconomic status, television viewing time and physical activity. RESULTS: Age
      and sex adjusted associations were similar in younger and older participants
      (Pinteraction all >0.05) and those with lower physical capability had higher
      mortality risk. For example, in those <70years old hazard ratios (95% confidence
      interval) for mortality in the third, second and lowest sex-specific quartiles of
      UWS compared to the highest were 1.21 (0.75, 1.96), 2.11 (1.35, 3.28) and 2.91
      (1.84, 4.62) and in participants >=70years old were 1.19 (0.73, 1.95), 2.09
      (1.35, 3.24) and 2.64 (1.73, 4.02) respectively. In the whole cohort, strong
      associations between all physical capability tests and mortality persisted after
      multivariable adjustment and after excluding participants with co-morbidity.
      CONCLUSIONS: Physical capability was independently predictive of future mortality
      risk with similar associations in late mid-life, when co-morbidity burden is
      lower, as at older age.

PMID- 29040889
TI  - Factors associated with happiness in the elderly persons living in the community.
AB  - OBJECTIVE: The aim of the present study was to evaluate factors associated with
      happiness in a sample of Brazilian older adults. METHODS: A study was conducted
      with 263 elderly people in the area of coverage of a family health unit located
      in the state of Sao Paulo, Brazil. The Subjective Happiness Scale was used to
      measure happiness, the final score of which determined one of three outcomes: not
      happy, intermediate, and happy. Disability, sociodemographic characteristics, and
      psychological, cognitive, and physical factors were considered for the
      multinomial logistic regression analysis. RESULTS: Statistically significant
      differences were found among the three groups regarding satisfaction with life,
      disability, social phobia, anxiety, depression, and frailty (p<=0.05). In the
      multinomial regression analysis, being "not happy" was significantly associated
      with satisfaction with life (RRR: 0.53), depression (RRR: 1.46), social phobia
      (RRR: 1.24), and age (RRR: 1.06). CONCLUSION: The present findings indicate that
      psychological factors and age influence the levels of happiness in older adults
      living in the community. Furthermore, better screening, diagnosis, and treatment
      of mental health disorders could increase the feeling of happiness among older
      adults.

PMID- 29040890
TI  - Omega-3 and omega-6 fatty acid levels in depressive and anxiety disorders.
AB  - BACKGROUND: Blood levels of polyunsaturated fatty acids (PUFAs) have been
      associated to current depression. However, it is unclear whether this association
      extends to remitted depression and to anxiety disorders. This study examined the
      relationship of PUFAs with the presence and clinical characteristics of
      depressive and anxiety disorders. METHODS: Cross-sectional data was used from the
      Netherlands Study of Depression and Anxiety, including persons with current pure
      depressive disorder (n=304), current pure anxiety disorder (n=548), current
      comorbid depressive and anxiety disorder (n=529), remitted depressive/anxiety
      disorder(s) (n=897), and healthy controls (n=634). Clinical characteristics
      included severity, subtypes, age of onset, duration of depression and anxiety and
      antidepressant use. Absolute values of omega-3 (N-3) and omega-6 (N-6) PUFAs and
      relative measures (as ratio of total Fatty Acids: the N-3:FA and N-6:FA ratio) in
      plasma were assessed using a nuclear magnetic resonance platform. RESULTS:
      Compared to controls, current comorbid depressive and anxiety disorder patients
      had lower N-3 PUFA levels (Cohen's d=0.09, p=0.012), and lower N-3:FA ratios
      (p=0.002, Cohen's d=0.11) as did current pure depressive disorder patients
      (Cohen's d=0.13, p=0.021), whereas N-6 PUFA levels were not different. No
      differences in PUFA levels were found between remitted patients and controls.
      Within patients, lower N-3 PUFA levels were only associated with higher
      depression severity (Beta=-0.42, p=0.023), whereas for N-6 PUFA levels and other
      clinical characteristics no clear association was observed. PUFA alterations were
      not associated with pure anxiety. CONCLUSION: It can be concluded that patients
      with a current depressive episode (especially the more severe cases with comorbid
      anxiety) have circulating N-3 PUFA levels lower than those in remission and
      healthy controls. No relationship was detected for N-6 PUFA levels.

PMID- 29040891
TI  - Acceptance lowers stress reactivity: Dismantling mindfulness training in a
      randomized controlled trial.
AB  - OBJECTIVE: Mindfulness interventions, which train practitioners to monitor their
      present-moment experience with a lens of acceptance, are known to buffer stress
      reactivity. Little is known about the active mechanisms driving these effects. We
      theorize that acceptance is a critical emotion regulation mechanism underlying
      mindfulness stress reduction effects. METHOD: In this three-arm parallel trial,
      mindfulness components were dismantled into three structurally equivalent 15
      lesson smartphone-based interventions: (1) training in both monitoring and
      acceptance (Monitor+Accept), (2) training in monitoring only (Monitor Only), or
      (3) active control training (Coping control). 153 stressed adults (mean
      age=32years; 67% female; 53% white, 21.5% black, 21.5% Asian, 4% other race) were
      randomly assigned to complete one of three interventions. After the intervention,
      cortisol, blood pressure, and subjective stress reactivity were assessed using a
      modified Trier Social Stress Test. RESULTS: As predicted, Monitor+Accept training
      reduced cortisol and systolic blood pressure reactivity compared to Monitor Only
      and control trainings. Participants in all three conditions reported moderate
      levels of subjective stress. CONCLUSIONS: This study provides the first
      experimental evidence that brief smartphone mindfulness training can impact
      stress biology, and that acceptance training drives these effects. We discuss
      implications for basic and applied research in contemplative science, emotion
      regulation, stress and coping, health, and clinical interventions.

PMID- 29040892
TI  - Majority of flat epithelial atypia diagnosed on biopsy do not require surgical
      excision.
AB  - BACKGROUND: Borderline risk lesions such as flat epithelial atypia (FEA) are
      increasingly being diagnosed on biopsy. The need for surgery is being debated. In
      this study, we determined the frequency of histological upgrade following a
      diagnosis of FEA on biopsy and evaluated potential predictive factors. METHODS:
      Retrospective review was done of 194 women who underwent biopsy of indeterminate
      lesions (total 195 lesions) that were diagnosed as FEA. The review covered a 10
      year period. Cases where malignancy was also present together with FEA within the
      same biopsy cores were excluded. RESULTS: Lesions diagnosed as FEA on biopsy were
      mostly asymptomatic and presented as microcalcifications on mammogram. Flat
      epithelial atypia was the only abnormality detected in one-third of cases, was
      associated with a benign or another borderline lesion in another third and was
      associated with atypical ductal hyperplasia (ADH) in another third. Six patients
      (3.1%) were later found to have ductal carcinoma-in-situ (DCIS) at surgery. The
      presence of ADH in the biopsy was the only predictor of histological upgrade to
      malignancy (P = 0.04, OR 11.24, 95% CI 1.10 - 115.10), and was present in 5 of
      the 6 patients. Surgery was advised in the last patient because of radiology
      pathology discordance. Thirty-six lesions (18.5%) were not excised and no
      interval progression or malignancy was found on follow up. CONCLUSION:
      Histological upgrade to malignancy was uncommon in lesions found on biopsy to be
      FEA. Non-operative management of biopsy-proven FEA can be considered in the
      absence of ADH and radiology-pathology discordance.

PMID- 29040893
TI  - Quality of online information on breast cancer treatment options.
AB  - Offering breast cancer patients treatment choice has become a priority as the
      involvement of patients in the decision-making process is associated with
      improved physical and psychological outcomes. As the Internet is increasingly
      being used by patients as a source of medical information, it is important to
      evaluate the quality of information relating to breast cancer on the Internet. We
      analysed 200 websites returned by google.co.uk searching "breast cancer treatment
      options" in terms of their typology and treatment options described. These were
      related to standard measures of health information quality such as the JAMA score
      and the presence of quality certifications, as well as readability. We found that
      health portals were of higher quality whilst commercial and professional websites
      were of poorer quality in terms of JAMA criteria. Overall, readability was higher
      than previously reported for other conditions, and Google ranked websites with
      better readability higher. Most websites discussed surgical and medical
      treatments. Few websites, with a large proportion being of commercial typology,
      discussed complementary and alternative medicine. Google ranked professional
      websites low whilst websites from non-profit organizations were promoted in the
      ranking.

PMID- 29040894
TI  - Demystifying endoscopic retrograde cholangiopancreatography (ERCP) during
      pregnancy.
AB  - BACKGROUND: For many years, ERCP was avoided in pregnancy given the concerns
      regarding the adverse effects that, with special focus on radiation, could occur
      in the developing fetus. However, the postponement or rejection of ERCP in
      pregnant women, may lead to a higher risk for mother and fetus, especially when
      the indication is unequivocal, namely cholangitis, biliary pancreatitis and
      symptomatic choledocholithiasis. SUMMARY AND KEY MESSAGES: This review aims to
      summarize the scarce literature on the subject in order to plan ERCP in pregnancy
      with the highest safety. The use of techniques that reduce radiation and increase
      the protection of pregnant women allow radiation levels far below the safety
      limits. We also discuss the various alternatives of ERCP without radiation. EUS
      can eliminate the need for ERCP with doubtful choledocholithiasis and plan the
      best approach in those with previous evidence. The possibility of performing
      "ERCP" with a linear echoendoscope uniquely under ultrasound control has been
      described. Conversely, the two-step strategy (initial sphincterotomy with stent
      placement without fluoroscopy and after delivery, ERCP with lithiasis extraction)
      proved to be safe obviating fluoroscopy. In conclusion, ERCP can be performed in
      pregnancy safely and effectively with minimal radiation or even no-radiation at
      all.

PMID- 29040895
TI  - Economic analysis of prenatal screening strategies for Down syndrome in singleton
      pregnancies in Turkey.
AB  - OBJECTIVES: To examine the costs and outcomes of different screening strategies
      for Down Syndrome (DS) in singleton pregnancies. STUDY DESIGN: A decision
      analytic model was developed to compare the costs and the outcomes of different
      prenatal screening strategies. Five strategies were compared for women under 35
      year of age: 1A) triple test (TT), 2A); combined test (CT), 3A) Non-invasive
      Prenatal Screening Test by using cell free fetal DNA (NIPT), 4A) and 5A) NIPT as
      a second-step screening for high-risk patients detected by either TT, or CT
      respectively. For women >=35-year of age, 1B) implementing invasive test
      (amniocentesis -AC) and 2B) NIPT for all women were compared. Data was analyzed
      to obtain the outcomes, total costs, the cost per women and the incremental cost
      effectiveness ratios (ICERs) for screening strategies. RESULTS: Among the current
      strategies for women under 35 years old, CT is clearly dominated to TT, as it is
      more effective and less costly. Although, the current routine practice (2A) is
      the least-costly strategy, implementing NIPT as a second step screening to high
      risk women identified by CT (5A) would be more effective than 2A; leading to a
      10.2% increase in the number of detected DS cases and a 96.3% reduction in
      procedural related losses (PRL). However, its cost to the Social Security
      Institution that is a public entity would be 17 times higher and increase
      screening costs by 1.5 times. Strategy 5A would result in an incremental cost
      effectiveness of 6,873,082 (PPP) US$ when compared to the current one (2A).
      Strategy 1B-for offering AC to all women >=35-year of age is dominated over NIPT
      (2B), as it would detect more DS cases and would be less costly. On the other
      hand, there would be 206 PRL associated with AC, but NIPT provides clear clinical
      benefits as there would be no PRL with NIPT. CONCLUSIONS: NIPT leads to very high
      costs despite its high effectiveness in terms of detecting DS cases and avoiding
      PRL. The cost of NIPT should be decreased, otherwise, only individuals who can
      afford to pay from out-of-pocket could benefit. We believe that reliable cost
      effective prenatal screening policies are essential in countries with low and
      smiddle income and high birth rates as well.

PMID- 29040896
TI  - Spillover effect of Japanese long-term care insurance as an employment promotion
      policy for family caregivers.
AB  - We evaluate a spillover effect of the Japanese public long-term care insurance
      (LTCI) as a policy to stimulate family caregivers' labor force participation.
      Using nationally representative data from 1995 to 2013, we apply difference-in
      difference propensity score matching to investigate the spillover effect in two
      periods: before and after the introduction of the LTCI in 2000 and before and
      after its major amendment in 2006. Our results show that the LTCI introduction
      has significant and positive spillover effects on family caregivers' labor force
      participation and the effects vary by gender and age. In contrast, the LTCI
      amendment is found to have generally negative spillover effects on their labor
      force participation. We draw attention to these spillover effects, as expanding
      labor market supply to sustain the economy would be a priority for Japan and
      other rapidly aging countries in the coming decades.

PMID- 29040897
TI  - Retirement and cognitive decline. A longitudinal analysis using SHARE data.
AB  - We show that a new measure of cognitive decline, that can be computed in
      longitudinal surveys where respondents perform the same recall memory tests over
      the years, is highly predictive of the onset of dementia. Using SHARE data, we
      investigate the way retirement affects cognitive decline over time controlling
      for age, education and other confounding factors. We find that retirement has a
      long-term detrimental effect on cognition for individuals who retire at the
      statutory eligibility age. It plays instead a protective role for those who
      retire on an early retirement scheme.

PMID- 29040898
TI  - Detailed effects of particle size and surface area on 222Rn emanation of a
      phosphate rock.
AB  - The dependency of radon emanation on soil texture was investigated using the
      closed chamber method. Ground phosphate rock with a large specific surface area
      was analyzed, and the presence of inner pores, as well as a high degree of
      roughness and heterogeneity in the phosphate particles, was found. The average
      radon emanation of the dry phosphate was 0.145 +/- 0.016. The emanation
      coefficient was highest (0.169 +/- 0.019) for the smallest particles (<25 MUm),
      decreasing to a constant value (0.091 +/- 0.014) for the larger particles (>210
      MUm). The reduction rate followed an inverse power law. As expected, a linear
      dependence between the emanation coefficient and the specific surface area was
      found, being lower than predicted for the large specific surface area. This was
      most likely due to an increase in the embedding effect of radon atoms in adjacent
      grains separated by micropores. Results indicate that knowledge of grain radium
      distribution is crucial to making accurate emanation predictions.

PMID- 29040899
TI  - Application of topographical source model for air dose rates conversions in
      aerial radiation monitoring.
AB  - After the Fukushima Daiichi Nuclear Power Station (FDNPS) accident in 2011,
      aerial radiation monitoring (ARM) using a manned helicopter was conducted to
      rapidly measure air dose rates and the deposition of radioactive nuclides over a
      large area. Typically, the air dose rate is obtained by conversion from the count
      rate using conventional flat source model (FSM). The converted dose rate obtained
      via aerial monitoring poorly matches the results of ground measurement in the
      mountain and forest areas because FSM does not consider topographical effects. To
      improve the conversion accuracy, we developed new methods to analyze aerial
      monitoring data using topographical source model (TSM) based on the analytical
      calculation of the gamma-ray flux. The ARM results converted using both FSM as
      well as TSM were compared with ground measurement data obtained after the FDNPS
      accident. By using TSM, the conversion accuracy was improved. In addition, to
      determine a parameter sensitive to topographical effects, we examined five
      parameters and it was clear that the difference between the elevation just below
      the helicopter and the mean elevation within the measurement area was the most
      influential.

PMID- 29040900
TI  - Alleviation of Cr(VI)-induced oxidative stress in maize (Zea mays L.) seedlings
      by NO and H2S donors through differential organ-dependent regulation of ROS and
      NADPH-recycling metabolisms.
AB  - Chromium (Cr) contamination in soil is a growing concern in relation to
      sustainable agricultural production and food safety. Nitric oxide (NO) and, more
      recently, hydrogen sulfide (H2S) are considered to be new signalling molecules
      with biotechnological applications in the agronomical sector. Using 9-day-old
      maize (Zea mays) seedlings exposed to 200MUM Cr(VI), the potential mitigating
      effects of exogenous NO and H2S on chromium-induced stress in maize seedlings
      were investigated in roots, cotyledons and coleoptiles. Analysis of Cr content,
      lipid peroxidation, antioxidant enzymes (catalase and superoxide dismutase
      isozymes), peroxisomal H2O2-producing glycolate oxidase and the main NADPH
      regenerating system revealed that chromium causes oxidative stress, leading to a
      general increase in these activities in coleptiles and roots, with the latter
      organ being the most affected. However, cotyledons behaved in an opposite manner.
      Moreover, exogenous applications of NO and H2S to Cr-stressed maize seedlings
      triggered a significant response, involving the virtual restoration of the values
      for all these activities to those observed in unstressed seedlings, although
      their specific impact on ROS and NADPH-recycling metabolisms depends on the
      seedling organ involved. Taken together, the data indicate that gas transmitters,
      NO and H2S, which act as a defence against the negative effects of hexavalent
      chromium contamination, are alternative compounds with potential biotechnological
      applications.

PMID- 29040901
TI  - High efficiency stratification of apple cultivar Ligol seed dormancy by
      phytohormones, heat shock and pulsed radio frequency.
AB  - The aim of the study was to improve the effect of stratification of apple "Ligol"
      seeds by application of selected compounds, phytohormones, and physical methods
      For this purpose the seeds were stratified at 3 degrees C in distilled water or
      in the presence of potassium nitrate (KNO3), ethephon (ET), carbon monoxide (CO),
      hydrogen peroxide (H2O2), a mixture of KNO3, ET, CO, H2O2, gibberellins (GA3), 6
      benzylaminopurine (BAP), jasmonic acid (JA), salicylic acid (SA) and a mixture of
      SA, GA3, BAP, JA, nitric oxide (NO), hydrogen chloride (HCL). Arranged protocols
      included various durations and combinations of selected compounds and
      phytohormones as well as laser and red light, heat shock - 2h heat shock (45
      degrees C) and Pulsed Radio Frequency (PRF) were investigated by germination
      tests and the activity of selected enzymes, gas exchange and index of chlorophyll
      in leaves. The obtained results showed the possibility to shorten more
      effectively the time of the apple 'Ligol' dormancy removal by treatments of the
      stratified seeds at 3 degrees C with different biological and physical methods
      Selected compounds and phytohormones acted collectively as a regulatory complex
      controlling the course of release from dormancy. Physical methods (PRF and heat
      shock) additionally contributed to dormancy breakage. Duration of phytohormones
      or compounds impacts during stratification should be prolonged to minimum 7days
      to assure more balanced conditions of the regulatory complex for the acceleration
      of dormancy a removal. The most beneficial results were obtained after seed
      stratification for 7days on filter paper moistened in KNO3+Etephon+CO+H2O2 at 3
      degrees C, and then on filter paper moistened in phytohormones (GA3+BAP+JA) till
      the end of seed germination (3 degrees C). The application of this protocol could
      be a very useful tool in a shortening the apple breeding cycle since the period
      of removing dormancy was reduced by 38days in comparison to stratified in water.
      PRF has also the additive role in breaking dormancy of apple 'Ligol' seed.
      Positive effects of compounds and phytohormones applied during stratification
      remarkably accelerated the growth of developed from them seedlings. Further
      research is needed to optimize stratification methods with appropriate contents
      and concentrations of compounds and phytohormones combined with PRF exposure.

PMID- 29040902
TI  - Primary Ewing's sarcoma of the kidney: A case report.
AB  - This is a 15-year-old female who presented with sudden onset left flank pain
      associated with nausea and vomiting and a history of weight loss. Radiological
      investigation revealed a large non-obstructive tumor involving the lower pole of
      the left kidney which was primarily thought to be a renal cell carcinoma. She
      underwent left open radical nephrectomy with adrenalectomy. Histopathology of the
      resected specimen showed features of Ewing's sarcoma of the kidney which was
      confirmed by cytogenetic analysis. This is a rare disease especially in the
      pediatric group and in reporting such a rare case we hope it helps in identifying
      a potential course of the disease and its response to the involved treatment.

PMID- 29040903
TI  - Aplasia cutis congenita as a result of interstitial laser therapy for fetal
      reduction in monochorionic twins: Conservative approach and outcome.
AB  - Monochorionic (MC) twin pregnancies are known to carry a high risk of twin-to
      twin transfusion syndrome (TTTS) that could lead to miscarriage and perinatal
      death. Demise of one fetus is frequently associated with co-fetal death. Fetal
      reduction by interstitial laser therapy is an effective procedure to prevent this
      outcome, but it may be associated with significant risks for both mother and
      fetus. Aplasia Cutis Congenita (ACC) may occur in up to 8% cases of fetal
      reduction by laser therapy. We report ACC in a preterm infant, a survivor of
      interstitial laser therapy for fetal reduction in MC pregnancy. Despite of
      massive skin lesions we were able to manage this case conservatively. Follow-up
      at 5 years of age revealed minimal scarring and no motor function limitations.

PMID- 29040904
TI  - Malignant fibrous histiocytoma in the right portion of the mandible with
      metastasis in pancreas.
AB  - BACKGROUND: Malignant fibrous histiocytoma is a sarcoma of uncertain origin that
      can be found both in soft tissues and in bones. It is currently called
      undifferentiated pleomorphic sarcoma not otherwise specified and it represents a
      final common pathway in several tumors that are subject to the progress of
      dedifferentiation. Local recurrence of the tumor in the same location where it
      was originated occurs in 20-30% of the total number of soft tissue sarcomas. It
      is less frequent in limbs and more likely to recur in retroperitoneal sarcomas
      and in head and neck. Most tumors grow during the first two years after
      treatment. Most sarcoma metastases, especially those in the head and neck
      (including malignant fibrous histiocytoma) present as a lung disease (90%).
      Extrapulmonary diseases are not frequent and can occur in lymph nodes (10%),
      bones (8%) and in the liver (1%). CASE REPORT: 61 years old woman with history of
      malignant fibrous histiocytoma in the right portion of the mandible, resected
      four years ago. Subsequent checkups did not show any disease. The patient reports
      a constant abdominal pain not diagnosed, related to a pancreatic nodule.
      CONCLUSION: Malignant fibrous histiocytoma is a potentially curable disease. The
      most important part of the treatment is complete surgical removal, usually
      followed by adjuvant radiation therapy. Chemotherapy is a treatment usually used
      only on those patients with higher recurrence risk or on those showingrecurrence
      or who have already showed recurrence.

PMID- 29040905
TI  - Bilateral methachronous testicular germ cell tumor and testicular microlithiasis
      in a child: Genetic analysis and insights. A case report.
AB  - OBJECTIVES: To report our experience with a case of a child with bilateral
      testicular micro-lithiasis (TML) who developed bilateral metachronous testicular
      germ cell tumor (TGCT) and determine the most appropriate follow-up and care
      management in children with testicular micro calcifications in regards to the
      theoretical risk of testicular cancer. CASE REPORT: A 12 year-old boy was
      diagnosed with TGCT and TML. Ten years after complete remission, he presented
      with a recurrence on the contralateral testis. Genetic screening was performed on
      both resected and the patient's karyotype was analyzed. RESULTS: Blood karyotype
      was normal. Aberrations were found in the tumor karyotype. CGH array showed
      alterations in chromosome arm 12p. DISCUSSION: TML is frequently associated with
      testicular malignancy in adults: in 16.9% of cases the normal contralateral
      testicle develops TML in TGCT. Recent works of literature find no relationship
      between TML and cancer in general, but in patients with additional risks, the
      relationship becomes stronger. Some authors suggest that environmental components
      and genetics are determinant factors. This is highly suspected in our reported
      case. It would seem that TML is not a precancerous lesion per se, but rather a
      marker of an at-risk situation. Long term evolution is uncertain and regular self
      palpation that starts before puberty is the only way to ensure proper screening
      and monitoring. CONCLUSION: TML have been suspected to be a sign of testicular
      dysgenesis syndrome, which yields a risk of developing TGCT in case of noxious
      associations. In patients with a history of TGCT contralateral TML is alarming
      and aggressive surgical management should be discussed. Therapeutic education of
      these patients on self-palpation is the best way to ensure proper follow-up.

PMID- 29040906
TI  - A case report of choledocholithiasis 33 years after cholecystectomy.
AB  - INTRODUCTION: Choledocholithiasis after cholecystectomy is rare and often
      attributed to surgical clip migration and subsequent nidus formation.
      PRESENTATION OF CASE: This case demonstrates choledocholithiasis following
      cholecystectomy with a latency period of 33 years. DISCUSSION: The patient
      presented with pain of the right upper quadrant (RUQ). Subsequent abdominal
      pelvic CT imaging revealed dilation of the common bile duct. Further Endoscopic
      Retrograde Cholangiopancreatography was indicative of choledocholithiasis.
      Additional findings included a long cystic duct remnant and surgical clips in the
      RUQ. CONCLUSION: The patient underwent biliary sphincterotomy and sludge and
      stone fragments were swept from the biliary tree. To our knowledge, a latency of
      33 years between cholecystectomy and choledocholithiasis has never been reported
      before, at least not in a patient without coexisting duodenal diverticulum, a
      condition associated with lithiasis of the common bile duct. Our case raises
      discussion of potential etiologies for such long latency, including surgical clip
      migration, remnant cystic duct lithiasis, and primary choledocholithiasis; and
      further details the incidence of such long latency periods following
      cholecystectomy.

PMID- 29040907
TI  - What do monkeys know about others' knowledge?
AB  - Recently, comparative psychologists have suggested that primates represent
      others' knowledge states. Evidence for this claim comes from studies
      demonstrating that primates expect others to maintain representations of objects
      when those objects are not currently visible. However, little work has explored
      whether nonhuman primates expect others to share the more sophisticated kinds of
      object knowledge that they themselves possess. We therefore investigated whether
      primates attribute to others knowledge that is acquired through the mental
      transformation of a static object representation. Specifically, we tested whether
      rhesus macaques (Macaca mulatta) expected a human demonstrator to solve a
      difficult rotational displacement task. In Experiment 1, monkeys watched a
      demonstrator hide a piece of fruit in one of two boxes. The monkey and the
      demonstrator then watched the boxes rotate 180 degrees . We found that monkeys
      looked longer when the demonstrator reached into the box that did not contain the
      fruit, indicating that they expected her to be able to track the fruit to its
      current location. In Experiment 2, we ruled out the possibility that monkeys
      simply expected the demonstrator to search for the food in its true location.
      When the demonstrator did not witness the rotation event, monkeys looked equally
      long at the two reaching outcomes. These results are consistent with the
      interpretation that rhesus macaques expect others to dynamically update their
      representations of unseen objects.

PMID- 29040908
TI  - Predicting lysine glycation sites using bi-profile bayes feature extraction.
AB  - Glycation is a nonenzymatic post-translational modification which has been found
      to be involved in various biological processes and closely associated with many
      metabolic diseases. The accurate identification of glycation sites is important
      to understand the underlying molecular mechanisms of glycation. As the
      traditional experimental methods are often labor-intensive and time-consuming, it
      is desired to develop computational methods to predict glycation sites. In this
      study, a novel predictor named BPB_GlySite is proposed to predict lysine
      glycation sites by using bi-profile bayes feature extraction and support vector
      machine algorithm. As illustrated by 10-fold cross-validation, BPB_GlySite
      achieves a satisfactory performance with a Sensitivity of 63.68%, a Specificity
      of 72.60%, an Accuracy of 69.63% and a Matthew's correlation coefficient of
      0.3499. Experimental results also indicate that BPB_GlySite significantly
      outperforms three existing glycation sites predictors: NetGlycate, PreGly and Gly
      PseAAC. Therefore, BPB_GlySite can be a useful bioinformatics tool for the
      prediction of glycation sites. A user-friendly web-server for BPB_GlySite is
      established at 123.206.31.171/BPB_GlySite/.

PMID- 29040910
TI  - Intensity inhomogeneity correction of SD-OCT data using macular flatspace.
AB  - Images of the retina acquired using optical coherence tomography (OCT) often
      suffer from intensity inhomogeneity problems that degrade both the quality of the
      images and the performance of automated algorithms utilized to measure structural
      changes. This intensity variation has many causes, including off-axis
      acquisition, signal attenuation, multi-frame averaging, and vignetting, making it
      difficult to correct the data in a fundamental way. This paper presents a method
      for inhomogeneity correction by acting to reduce the variability of intensities
      within each layer. In particular, the N3 algorithm, which is popular in
      neuroimage analysis, is adapted to work for OCT data. N3 works by sharpening the
      intensity histogram, which reduces the variation of intensities within different
      classes. To apply it here, the data are first converted to a standardized space
      called macular flat space (MFS). MFS allows the intensities within each layer to
      be more easily normalized by removing the natural curvature of the retina. N3 is
      then run on the MFS data using a modified smoothing model, which improves the
      efficiency of the original algorithm. We show that our method more accurately
      corrects gain fields on synthetic OCT data when compared to running N3 on non
      flattened data. It also reduces the overall variability of the intensities within
      each layer, without sacrificing contrast between layers, and improves the
      performance of registration between OCT images.

PMID- 29040909
TI  - Treatment with Fenofibrate plus a low dose of Benznidazole attenuates cardiac
      dysfunction in experimental Chagas disease.
AB  - Trypanosoma cruzi induces serious cardiac alterations during the chronic
      infection. Intense inflammatory response observed from the beginning of
      infection, is critical for the control of parasite proliferation and evolution of
      Chagas disease. Peroxisome proliferator-activated receptors (PPAR)-alpha, are
      known to modulate inflammation. In this study we investigated whether a PPAR
      alpha agonist, Fenofibrate, improves cardiac function and inflammatory parameters
      in a murine model of T. cruzi infection. BALB/c mice were sequentially infected
      with two T. cruzi strains of different genetic background. Benznidazole, commonly
      used as trypanocidal drug, cleared parasites but did not preclude cardiac
      pathology, resembling what is found in human chronic chagasic cardiomyopathy.
      Fenofibrate treatment restored to normal values the ejection and shortening
      fractions, left ventricular end-diastolic, left ventricular end-systolic
      diameter, and isovolumic relaxation time. Moreover, it reduced cardiac
      inflammation and fibrosis, decreased the expression of pro-inflammatory (IL-6,
      TNF-alpha and NOS2) and heart remodeling mediators (MMP-9 and CTGF), and reduced
      serum creatine kinase activity. The fact that Fenofibrate partially inhibited
      NOS2 expression and NO release in the presence of a PPAR-alpha non-competitive
      inhibitor, suggested it also acted through PPAR-alpha-independent pathways. Since
      IkappaBalpha cytosolic degradation was inhibited by Fenofibrate, it can be
      concluded that the NFkappaB pathway has a role in its effects. Thus, we
      demonstrate that Fenofibrate acts through PPAR-alpha-dependent and -independent
      pathways. Our study shows that combined treatment with Fenofibrate plus
      Benznidazole is able both to reverse the cardiac dysfunction associated with the
      ongoing inflammatory response and fibrosis and to attain parasite clearance in an
      experimental model of Chagas disease.

PMID- 29040912
TI  - Establishment of an induced pluripotent stem (iPS) cell line from dermal
      fibroblasts of an asymptomatic patient with dominant PRPF31 mutation.
AB  - A human iPS cell line was generated from fibroblasts of a phenotypically
      unaffected patient from a family with PRPF31-associated retinitis pigmentosa
      (RP). The transgene-free iPS cells were generated with the human OSKM
      transcription factors using the Sendai-virus reprogramming system. iPS cells
      contained the expected c.709-734dup substitution in exon 8 of PRPF31, expressed
      the expected pluripotency markers, displayed in vivo differentiation potential to
      the three germ layers and had normal karyotype. This cellular model will provide
      a powerful tool to study the unusual pattern of inheritance of PRPF31-associated
      RP.

PMID- 29040911
TI  - A deep learning model integrating FCNNs and CRFs for brain tumor segmentation.
AB  - Accurate and reliable brain tumor segmentation is a critical component in cancer
      diagnosis, treatment planning, and treatment outcome evaluation. Build upon
      successful deep learning techniques, a novel brain tumor segmentation method is
      developed by integrating fully convolutional neural networks (FCNNs) and
      Conditional Random Fields (CRFs) in a unified framework to obtain segmentation
      results with appearance and spatial consistency. We train a deep learning based
      segmentation model using 2D image patches and image slices in following steps: 1)
      training FCNNs using image patches; 2) training CRFs as Recurrent Neural Networks
      (CRF-RNN) using image slices with parameters of FCNNs fixed; and 3) fine-tuning
      the FCNNs and the CRF-RNN using image slices. Particularly, we train 3
      segmentation models using 2D image patches and slices obtained in axial, coronal
      and sagittal views respectively, and combine them to segment brain tumors using a
      voting based fusion strategy. Our method could segment brain images slice-by
      slice, much faster than those based on image patches. We have evaluated our
      method based on imaging data provided by the Multimodal Brain Tumor Image
      Segmentation Challenge (BRATS) 2013, BRATS 2015 and BRATS 2016. The experimental
      results have demonstrated that our method could build a segmentation model with
      Flair, T1c, and T2 scans and achieve competitive performance as those built with
      Flair, T1, T1c, and T2 scans.

PMID- 29040913
TI  - Generation of human erythroblast-derived iPSC line using episomal reprogramming
      system.
AB  - Peripheral blood mononuclear cells were isolated and cultured to a pure pro-EBL
      population and reprogrammed using episomal plasmids. The pluripotency of
      transgene-free induced pluripotent stem cell (iPSC) line was verified by the
      expression of pluripotency-associated markers and by in vitro spontaneous
      differentiation towards the 3 germ layers. The iPSC line showed normal karyotype.
      Peripheral blood is a non-invasive easy accessible cell source and combined with
      EBL outgrowth in vitro, a routine process obtaining sufficient amount of
      homogenous cells can be obtained within a week. Using episomal delivery, pro-EBLs
      can be reprogrammed in a transgene-free, cost effective system.

PMID- 29040914
TI  - Efficient capture, rapid killing and ultrasensitive detection of bacteria by a
      nano-decorated multi-functional electrode sensor.
AB  - In this work, we demonstrated a nano-decorated porous impedance electrode sensor
      for efficient capture, rapid killing and ultrasensitive detection of bacteria.
      The multi-functional sensor was prepared by a facile sonochemical method via in
      situ deposition of antibacterial prickly Zn-CuO nanoparticles and graphene oxide
      (GO) nanosheets on a Ni porous electrode. Due to the surface burr-like
      nanostructures, the nano-decorated impedance sensor exhibited very good bacterial
      capture efficiency (70 - 80% in 20min) even at a low concentration of 50 CFU mL
      1, rapid antibacterial rate (100% killing in 30min) and high detection
      sensitivity (as low as 10 CFU mL-1). More importantly, the nano-decorated sensor
      has proven to be highly effective in quantitative detection of bacteria in a
      biological sample, for example, a rat blood sample spiked with E. coli. Despite
      the complexity of blood, the sensor still exhibited excellent detection precision
      within 30min at bacteria concentrations ranging from 10 - 105 CFU mL-1. The
      simplicity, rapidity, sensitivity, practicability and multifunctionality of this
      impedance sensor would greatly facilitate applications in portable medical
      devices for on-the-spot diagnosis and even the possibility for simultaneous
      therapy of diseases caused by bacterial infections.

PMID- 29040915
TI  - A novel three-dimensional carbonized PANI1600@CNTs network for enhanced enzymatic
      biofuel cell.
AB  - A novel three-dimensional (3D) carbon composite of PANI1600@CNTs with rhizobium
      like structure is prepared by in-situ polymerization of aniline monomers around
      and along the functionalized carbon nanotubes (CNTs) and then carbonized at 1600
      degrees C for enzymatic biofuel cells (EBFCs). The SEM and TEM images clearly
      show that the carbonized PANI grew seamlessly on the surface of CNTs and
      presented the rhizobium-like structure. The carbonized PANI acts like conductive
      "glue" and connects the adjacent tubes together, which can assemble the CNTs into
      a 3D network. The PANI1600@CNTs composite modified glassy carbon electrodes based
      on glucose oxidase (GOx) and laccase (Lac) exhibit high electrochemical
      performance. A glucose//O2 EBFC constitutes of the fabricated anode and cathode
      performs a maximum power density of 1.12mWcm-2 at 0.45V. Furthermore, three of
      the fabricated EBFCs in series are able to lightening up a yellow light-emitting
      diode (LED) whose turn-on voltage is about at 1.8V. This work may be helpful for
      exploiting novel substrates by carbonizing the composites of conducting polymer
      with nano materials at high-temperature for immobilization of enzymes in the
      EBFCs or biosensor fields.

PMID- 29040916
TI  - Versatile on-stage microfluidic system for long term cell culture,
      micromanipulation and time lapse assays.
AB  - We report here a versatile on-stage microfluidic cell culture and assay system
      which is compatible with different microscopes and sensors, can simultaneously
      perform steps of long term cell culture, high throughput time lapse cell
      assays/imaging, and cell micromanipulations. With the system, we cultured a
      variety of cells for different periods of time and monitored their cell
      morphology, migration and division. We also performed a series non-invasive real
      time in situ time lapse assays and micromanipulations on different cells. They
      include: the first time lapse imaging and measurements on the instantaneous
      variations of morphology, biomechanical properties and the intracellular protein
      of human red blood cells in responding to pH fluctuation, drug action and
      electromagnetic radiation; the first continuous time lapse Raman micro
      spectroscopy on a CHO cell in different phases of its entire life cycles; the
      micro-transfection of GFP into B16 cells and the follow up observation of the
      cell's morphology and expressed GFP fluorescence varying with incubation time and
      cell generations. The performance of these experiments not only demonstrated the
      capability of the system, but also proposed a variety of novel methods for
      obtaining time- and spatially-resolved information about the cellular and
      molecular heterogeneity and transformation during development or stimulations.

PMID- 29040917
TI  - Enhanced diffusometric immunosensing with grafted gold nanoparticles for
      detection of diabetic retinopathy biomarker tumor necrosis factor-alpha.
AB  - Diffusometry is sensitive to geometric changes of particles. Target antigens can
      be detected through diffusivity changes resulting from their immunoreactions by
      functionalizing particle surface with a specific antibody. Considering that
      Brownian motion is a self-driven phenomenon, diffusometric immunosensing features
      several characteristics, such as no-washing steps, rapid detection, high
      flexibility, and high sensitivity. Until recently, this technique has been
      applied to many biomedical fields, such as monitoring of microorganism motility
      and diagnosis of diseases with biomarkers. Despite the abovementioned advantages,
      diffusivity changes in conventional diffusometry can be compromised at low
      abundance antigens because proteins are much smaller than capture particles. To
      overcome such restriction, we present an improved diffusometric immunosensing
      technique by grafting additional gold nanoparticles (AuNPs) to capture particles
      to enhance size changes. A diabetic retinopathy (DR) biomarker, tumor necrosis
      factor-alpha was selected to evaluate the proposed immunosensing technique.
      Spherical AuNPs showed better enhancement than rod-like AuNPs during measurement.
      Limit of detection was improved by at least 100-fold down to 10pg/mL. A
      dichotomous method was also developed to enable rapid detection and avoid tedious
      calibration. The relationship of concentrations between the two solutions used
      can be explicitly determined by comparing diffusivity of an unknown concentration
      of target molecules with that of a reference solution. Minimum discernible
      concentration reached as low as twofold higher or lower than basal concentration.
      Tear samples were collected from four volunteers, including three healthy
      subjects and one proliferative DR patient to prove the concept in diagnosis of
      the disease. All data showed good agreement with preset conditions. The technique
      eventually provides an insight into rapid diagnoses of diseases in the early
      stage.

PMID- 29040918
TI  - Tumor cryoablation in combination with natural killer cells therapy and Herceptin
      in patients with HER2-overexpressing recurrent breast cancer.
AB  - In this study, we investigated the clinical benefits of a combination of tumor
      cryoablation with natural killer (NK) cells therapy and Herceptin for human
      epidermal growth factor (HER) 2-overexpressing recurrent breast cancer. From May
      2015 to May 2016, 48 patients who met the enrollment criteria were assigned to
      three groups (n=16): cryoablation group (group I), cryoablation-NK cells therapy
      group (group II) and cryoablation-NK cells therapy-Herceptin group (group III).
      Safety and short-term effects were evaluated. All the adverse effects were
      manageable and acceptable. The three-therapy combination treatment not only
      yielded good clinical efficacy, it also improved the quality of life; reduced
      levels of circulating tumor cells (CTCs); reduced carcino-embryonic antigen (CEA)
      and cancer antigen 15-3 (CA15-3) expression; enhanced immune function
      significantly. Furthermore, it can resulte in significant prolongation of
      progression free survival (PFS). This is the first clinical study to demonstrate
      the benefit of the three-therapy combination of tumor cryoablation, NK cells
      therapy, and Herceptin for HER2-overexpressing recurrent breast cancer.

PMID- 29040920
TI  - Ancestry prediction in Singapore population samples using the Illumina ForenSeq
      kit.
AB  - The ability to predict bio-geographic ancestry can be valuable to generate
      investigative leads towards solving crimes. Ancestry informative marker (AIM)
      sets include large numbers of SNPs to predict an ancestral population. Massively
      parallel sequencing has enabled forensic laboratories to genotype a large number
      of such markers in a single assay. Illumina's ForenSeq DNA Signature Kit includes
      the ancestry informative SNPs reported by Kidd et al. In this study, the ancestry
      prediction capabilities of the ForenSeq kit through sequencing on the MiSeq FGx
      were evaluated in 1030 unrelated Singapore population samples of Chinese, Malay
      and Indian origin. A total of 59 ancestry SNPs and phenotypic SNPs with AIM
      properties were selected. The bio-geographic ancestry of the 1030 samples, as
      predicted by Illumina's ForenSeq Universal Analysis Software (UAS), was
      determined. 712 of the genotyped samples were used as a training sample set for
      the generation of an ancestry prediction model using STRUCTURE and Snipper. The
      performance of the prediction model was tested by both methods with the remaining
      318 samples. Ancestry prediction in UAS was able to correctly classify the
      Singapore Chinese as part of the East Asian cluster, while Indians clustered with
      Ad-mixed Americans and Malays clustered in-between these two reference
      populations. Principal component analyses showed that the 59 SNPs were only able
      to account for 26% of the variation between the Singapore sub-populations. Their
      discriminatory potential was also found to be lower (GST=0.085) than that
      reported in ALFRED (FST=0.357). The Snipper algorithm was able to correctly
      predict bio-geographic ancestry in 91% of Chinese and Indian, and 88% of Malay
      individuals, while the success rates for the STRUCTURE algorithm were 94% in
      Chinese, 80% in Malay, and 91% in Indian individuals. Both these algorithms were
      able to provide admixture proportions when present. Ancestry prediction accuracy
      (in terms of likelihood ratio) was generally high in the absence of admixture.
      Misclassification occurred in admixed individuals, who were likely offspring of
      inter-ethnic marriages, and hence whose self-reported bio-geographic ancestries
      were dependent on that of their fathers, and in individuals of minority sub
      populations with inter-ethnic beliefs. The ancestry prediction capabilities of
      the 59 SNPs on the ForenSeq kit were reasonably effective in differentiating the
      Singapore Chinese, Malay and Indian sub-populations, and will be of use for
      investigative purposes. However, there is potential for more accurate prediction
      through the evaluation of other AIM sets.

PMID- 29040919
TI  - Functional analyses of the interaction of chicken interleukin 23 subunit p19 with
      IL-12 subunit p40 to form the IL-23 complex.
AB  - This study represents the first description of the cloning of chicken IL-23p19
      (ChIL-23alpha) and the function of the IL-23 complex in birds. Multiple alignment
      of ChIL-23alpha with other known IL-23alpha amino acid sequences revealed regions
      of amino acid conservation. The homologies of ChIL-23alpha, IL-12p35, and similar
      mammalian subunits ranged between 26% and 42%. ChIL-23alpha consisted of four
      exons and three introns; similar to those in humans and mice, and limited
      conservation of synteny between the human and chicken genomes was observed. Using
      bioinformatics tools, we identified the NF-kappaB, C/EBPalpha-beta, c-Jun, c-Rel,
      AP-1, GATA-1, and ER promoter sites in ChIL-23alpha. Moreover, IL-23alpha mRNA
      was more highly expressed than IL-12p40 and IL-12p35 mRNA in several organs of
      chickens infected with Salmonella. In addition, ChIL-23 complex are associated
      with IL-23R, IL-12Rbeta1 receptors; activate the JAK2/TYK2, STAT1/3, SOCS1 genes,
      and induced proinflammatory cytokines in immune cells. Collectively, these
      results indicate that ChIL-23 is a member of the IL-12 family, has
      proinflammatory properties related to IL-23R and IL-12Rbeta1 receptor expression,
      and activates the JAK/STAT signaling pathway that results in the interaction of
      ChIL-23alpha with ChIL-12p40 to form the novel ChIL-23 complex. Our results
      provide novel insights into the regulation of immunity, inflammation, and
      immunopathology.

PMID- 29040921
TI  - Effect of local cooling on excitation-contraction coupling in myasthenic muscle:
      Another mechanism of ice-pack test in myasthenia gravis.
AB  - OBJECTIVE: The ice-pack test is a convenient diagnostic testing procedure for
      myasthenia gravis (MG). We investigated the underlying mechanism of the ice-pack
      test performed on bilateral masseters. METHODS: We performed trigeminal
      repetitive nerve stimulation (RNS), excitation-contraction (E-C) coupling
      assessment (Imai's method) and bite force measurement before and after cooling of
      the masseters in MG patients and normal controls. After placing the ice-pack on
      the masseters for 3min, serial recordings of the three tests were performed at
      various time intervals during 10min after cooling. RESULTS: The bite force
      increased significantly after cooling in ice-pack-positive MG patients. The
      acceleration and acceleration ratio (acceleration at a given time to baseline
      acceleration) of jaw movement increased significantly after cooling of the
      masseters in ice-pack-positive MG patients compared to ice-pack-negative patients
      and normal controls. The prolonged effect of cooling continued until the end of
      recording even though decremental response to RNS had returned to baseline value.
      CONCLUSIONS: Cooling of myasthenic muscle may induce two effects. One is
      relatively short effect on electrical synaptic transmission at the endplate, and
      another is prolonged effect on E-C coupling in the muscle. SIGNIFICANCE: The ice
      pack test induces a prolonged effect of ameliorating impaired E-C coupling in MG.

PMID- 29040922
TI  - Plasticity induced by non-invasive transcranial brain stimulation: A position
      paper.
AB  - Several techniques and protocols of non-invasive transcranial brain stimulation
      (NIBS), including transcranial magnetic and electrical stimuli, have been
      developed in the past decades. Non-invasive transcranial brain stimulation may
      modulate cortical excitability outlasting the period of non-invasive transcranial
      brain stimulation itself from several minutes to more than one hour. Quite a few
      lines of evidence, including pharmacological, physiological and behavioral
      studies in humans and animals, suggest that the effects of non-invasive
      transcranial brain stimulation are produced through effects on synaptic
      plasticity. However, there is still a need for more direct and conclusive
      evidence. The fragility and variability of the effects are the major challenges
      that non-invasive transcranial brain stimulation currently faces. A variety of
      factors, including biological variation, measurement reproducibility and the
      neuronal state of the stimulated area, which can be affected by factors such as
      past and present physical activity, may influence the response to non-invasive
      transcranial brain stimulation. Work is ongoing to test whether the reliability
      and consistency of non-invasive transcranial brain stimulation can be improved by
      controlling or monitoring neuronal state and by optimizing the protocol and
      timing of stimulation.

PMID- 29040923
TI  - Six factors of adult dyslexia assessed by cognitive tests and self-report
      questions: Very high predictive validity.
AB  - The Multiple Diagnostic Digital Dyslexia Test for Adults (MDDDT-A) consists of 12
      newly developed tests and self-report questions in the Dutch language. Predictive
      validity and construct validity were investigated and compared with validity of a
      standard test battery of dyslexia (STB) in a sample of 154 students. There are
      three main results. First, various analyses of principal components showed that
      six or more factors of dyslexia can be distinguished (rapid naming, spelling,
      reading, short-term memory, confusion, phonology, attention, complexity). All
      factors are represented by the MDDDT-A. Second, various discriminant analyses
      showed good predictive validity for both the tests of the MDDDT-A (90%) and the
      STB (90%). However, predictive validity of the questionnaire was highest (97%).
      Third, we analysed the best predictors of dyslexia and found that predictive
      validity is higher when construct validity is high, that is when a set of
      predictors represents many characteristics of dyslexia. The main conclusion is
      that a digital test battery can be a reliable screening instrument for dyslexia
      in students, especially when it is accompanied by self-report questions. A
      theoretical conclusion is that dyslexia is characterized by at least six
      cognitive impairments in a complex way. In students, this structure may be
      modulated by high intelligence and good schooling through various compensation
      strategies. It is therefore recommended to include assessments of all
      characteristics of dyslexia to achieve the most reliable diagnoses in different
      samples and in different countries.

PMID- 29040924
TI  - Early social communication in infants with fragile X syndrome and infant siblings
      of children with autism spectrum disorder.
AB  - BACKGROUND: Little research in fragile X syndrome (FXS) has prospectively
      examined early social communication. AIMS: To compare early social communication
      in infants with FXS, infant siblings of children with autism spectrum disorder
      (ASIBs), and typically developing (TD) infants. METHODS AND PROCEDURES:
      Participants were 18 infants with FXS, 21 ASIBs, and 22 TD infants between 7.5
      14.5 months. Social communication was coded using the Communication Complexity
      Scale during the administration of Autism Observation Scale for Infants. OUTCOMES
      AND RESULTS: Descriptively different patterns were seen across the three groups.
      Overall infants with FXS had lower social communication than ASIBs or TD infants
      when controlling for nonverbal cognitive abilities. However, infants with FXS had
      similar levels of social communication as ASIBs or TD infants during peek-a-boo.
      No differences were observed between ASIBs and TD infants. For all infants,
      higher social communication was related to lower ASD risk. CONCLUSIONS AND
      IMPLICATIONS: Findings provide insight into the developmental course of social
      communication in FXS. The dynamic nature of social games may help to stimulate
      communication in infants with FXS. Language interventions with a strong social
      component may be particularly effective for promoting language development in
      FXS.

PMID- 29040925
TI  - The natural number bias and its role in rational number understanding in children
      with dyscalculia. Delay or deficit?
AB  - BACKGROUND: Previous research indicated that in several cases learners' errors on
      rational number tasks can be attributed to learners' tendency to (wrongly) apply
      natural number properties. There exists a large body of literature both on
      learners' struggle with understanding the rational number system and on the role
      of the natural number bias in this struggle. However, little is known about this
      phenomenon in learners with dyscalculia. AIMS: We investigated the rational
      number understanding of learners with dyscalculia and compared it with the
      rational number understanding of learners without dyscalculia. METHOD: Three
      groups of learners were included: sixth graders with dyscalculia, a chronological
      age match group, and an ability match group. RESULTS: The results showed that the
      rational number understanding of learners with dyscalculia is significantly lower
      than that of typically developing peers, but not significantly different from
      younger learners, even after statistically controlling for mathematics
      achievement. CONCLUSION: Next to a delay in their mathematics achievement,
      learners with dyscalculia seem to have an extra delay in their rational number
      understanding, compared with peers. This is especially the case in those rational
      number tasks where one has to inhibit natural number knowledge to come to the
      right answer.

PMID- 29040926
TI  - A rapid, naked-eye detection of hypochlorite and bisulfite using a robust and
      highly-photostable indicator dye Quinaldine Red in aqueous medium.
AB  - A "naked-eye" detection of health hazardous bisulfite (HSO3-) and hypochlorite
      (ClO-) using an indicator dye (Quinaldine Red, QR) in a wide range of pH is
      demonstrated. The molecule contains a quinoline moiety linked to an N,N
      dimethylaniline moiety with a conjugated double bond. Treatment of QR with HSO3-
      and ClO-, in aqueous solution at near-neutral pH, resulted in a colorless product
      with high selectivity and sensitivity. The detection limit was 47.8MUM and 0.2MUM
      for HSO3- and ClO- respectively. However, ClO- was 50 times more sensitive and
      with 2 times faster response compared to HSO3-. The detail characterization and
      related analysis demonstrate the potential of QR for a rapid, robust and highly
      efficient colorimetric sensor for the practical applications to detect
      hypochlorite in water samples.

PMID- 29040927
TI  - Combination of hollow fluorescent carbon and gold nanoparticles: A super
      catalyst.
AB  - Hollow fluorescent carbon nanoparticles (HFCNs) have been combined with gold
      nanoparticles (AuNPs) to produce a special catalyst. The catalytic properties of
      HFCNs and AuNPs were exploited to conceptualize the new catalytic functionality.
      The AuNP-embedded-HFCNs produced in situ were found to massively enhance the rate
      of reduction of 4-nitrophenol (a model reaction) in presence of sodium
      borohydride. Comparison with functioning of other nanoparticulate catalysts on
      the same reaction proved our product to be an extremely efficient catalyst.

PMID- 29040928
TI  - Calorimetric and spectroscopic studies of the interaction between zidovudine and
      human serum albumin.
AB  - A quantitative analysis of the interaction between zidovudine (AZT) and human
      serum albumin (HSA) was achieved using Isothermal titration calorimetry (ITC) in
      combination with fluorescence and 1H NMR spectroscopy. ITC directly measure the
      heat during a biomolecular binding event and gave us thermodynamic parameters and
      the characteristic association constant. By fluorescence quenching, the binding
      parameters of AZT-HSA interaction was determined and location to binding site I
      of HSA was confirmed. Via T1 NMR selective relaxation time measurements the drug
      protein binding extent was evaluated as dissociation constants Kd and the
      involvement of azido moiety of zidovudine in molecular complex formation was put
      in evidence. All three methods indicated a very weak binding interaction. The
      association constant determined by ITC (3.58*102M-1) is supported by fluorescence
      quenching data (2.74*102M-1). The thermodynamic signature indicates that at least
      hydrophobic and electrostatic type interactions played a main role in the binding
      process.

PMID- 29040929
TI  - Determination of geographical origin and icariin content of Herba Epimedii using
      near infrared spectroscopy and chemometrics.
AB  - Near infrared (NIR) spectroscopy coupled with chemometrics was used to
      discriminate the geographical origin of Herba Epimedii in this work. Four
      different classification models, namely discriminant analysis (DA), back
      propagation neural network (BPNN), K-nearest neighbor (KNN), and support vector
      machine (SVM), were constructed, and their performances in terms of recognition
      accuracy were compared. The results indicated that the SVM model was superior
      over the other models in the geographical origin identification of Herba
      Epimedii. The recognition rates of the optimum SVM model were up to 100% for the
      calibration set and 94.44% for the prediction set, respectively. In addition, the
      feasibility of NIR spectroscopy with the CARS-PLSR calibration model in
      prediction of icariin content of Herba Epimedii was also investigated. The
      determination coefficient (RP2) and root-mean-square error (RMSEP) for prediction
      set were 0.9269 and 0.0480, respectively. It can be concluded that the NIR
      spectroscopy technique in combination with chemometrics has great potential in
      determination of geographical origin and icariin content of Herba Epimedii. This
      study can provide a valuable reference for rapid quality control of food
      products.

PMID- 29040930
TI  - DFT computations on: Crystal structure, vibrational studies and optical
      investigations of a luminescent self-assembled material.
AB  - The current work undertakes the growth and the physicochemical properties of a
      novel green-yellow luminescence semi-organic material, the 3-picolylammonium
      bromide abbreviated (Pico-Br). In this paper, we report the X-ray diffraction
      measurements which show that the crystal lattice consists of distinct 3
      picolylammonium cations and free bromide anions connected via NH?Br and NH?N
      hydrogen bonds leading to form a two dimensional frameworks. Molecular geometry
      compared with its optimized counterpart shows that the quantum chemical
      calculations carried out with density functional method (DFT) well produce the
      perceived structure by X-ray resolution of the studied material. To provide
      further insight into the spectroscopic properties, additional characterization of
      this material have been performed with Raman and infrared studies at room
      temperature. Theoretical computations have been computed using the (DFT) method
      at B3LYP/LanL2DZ level of theory implemented within Gaussian 03 program to study
      the vibrational spectra of the investigated molecule in the ground state. Optical
      absorption spectrum inspected by UV-visible absorption reveals the appearance of
      sharp optical gap of 280nm (4.42eV) as well as a strong green photoluminescence
      emission at 550nm (2.25eV) is detected on the photoluminescence (PL) spectrum at
      room temperature. Using the TD/DFT method, HOMO-LUMO energy gap and the Mulliken
      atomic charges were calculated in order to get an insight into the material. Good
      agreement between the theoretical results and the experimental ones was
      predicted.

PMID- 29040931
TI  - A combined experimental (IR, Raman and UV-Vis) and quantum chemical study of
      canadine.
AB  - Plant based natural products cover a major sector of the medicinal field, as such
      focus on plant research has been increased all over the world. As an attempt to
      aid that research, we have performed structural and spectroscopic analysis of a
      natural product, an alkaloid: canadine. Both ab initio Hartree-Fock (HF) and
      density functional theory (DFT) employing B3LYP using 6-311++G(d,p) basis set
      were used for the calculations. The calculated vibrational frequencies were
      scaled and compared with the experimental infrared and Raman spectra. The
      complete vibrational assignments were made using potential energy distribution.
      The structure-activity relation has also been interpreted by mapping
      electrostatic potential surface and evaluating the reactivity descriptors, which
      are valuable information for quality control of medicines and drug-receptor
      interactions. Natural bond orbital analysis has also been performed to understand
      the stability and hyperconjugative interactions of the molecule. Furthermore, UV
      Vis spectra have been recorded in an ethanol solvent (EtOH) and the electronic
      property has been analyzed employing TD-DFT for both gaseous and solvent phase.
      The HOMO and LUMO calculation with their energy gap show that charge transfer
      occurs within the molecule. Additionally, the nonlinear optical properties of the
      title compound have been interpreted that predicts it's the best candidate for
      the NLO materials.

PMID- 29040932
TI  - Fabrication of porous covalent organic frameworks as selective and advanced
      adsorbents for the on-line preconcentration of trace elements against the complex
      sample matrix.
AB  - Herein, for the first time, the typical porous Covalent Organic Frameworks (COFs)
      CTpBD with superior chemical stability and large surface area were applied as
      sorbents for solid phase extraction of trace ions via flow injection followed by
      inductively coupled plasma mass spectrometry (ICP-MS) detection. The well
      prepared and fully-characterized CTpBD COFs were filled in solid phase extraction
      cartridge as novel and robust adsorbents for element analysis. Separation and
      enrichment of Cr (III), Mn (II), Co (II), Ni (II), Cd (II), V (V), Cu (II), As
      (III), Se (IV), and Mo (VI) was then carried out, and the contents were measured
      by ICP-MS. Owing to the large surface area and instinctive porous structure of
      CTpBD, preconcentration of the target trace elements via COF-filled on-line SPE
      column has achieved low detection limits of 2.1-21.6ngL-1 along with a wide
      linearity range at 0.05-25MUgL-1 for all target ions. The relative standard
      deviations (RSD) of 1.2%-4.3% obtained via 11 parallel determinations at the
      sample concentration of 100ngL-1 revealed excellent repeatability of the
      developed methods Our proposed methods have been successfully utilized for trace
      element analysis in environmental and food samples.

PMID- 29040933
TI  - Evaluation of MnO2-templated iron oxide-coated diatomites for their catalytic
      performance in heterogeneous photo Fenton-like system.
AB  - Herein, iron oxide-coated diatomites were prepared through hydrothermal synthesis
      and sacrificial template redox etching reaction. The microstructure
      characterization results revealed that the Fe2O3 nanorods were uniformly
      distributed on the surface of diatomite. The effects of diverse synthetic
      parameters on morphology of as-synthesized Fe2O3@diatomite were investigated.
      When the reaction time was prolonged from 12h to 24h, the morphology of FeOOH
      would change from nanorods into nanoflowers. Two different crystal phases of
      Fe2O3@diatomite were obtained from the FeOOH@diatomite samples calcined under
      different atmospheres. The catalytic activity of alpha-Fe2O3@diatomite was
      evaluated by the heterogeneous photo Fenton-like system through degradation of
      methylene blue (MB, 10 - 40mgL-1) in the presence of hydrogen peroxide (H2O2, 9mM
      - 120mM) under UV light irradiation. It was found that alpha-Fe2O3@diatomite
      composites showed very excellent degradation efficiency, which was about 99%
      within 120min under UV irradiation. This catalyst extended the range of pH values
      of homogeneous Fenton reaction, in which the MB removal rate was maintained over
      80.8%. Moreover, the alpha-Fe2O3@diatomite catalyst still showed sound
      reusability after 5 rounds of degradation of MB dye. In principles, a possible
      photo-catalytic mechanism was proposed to testify metal oxides composites for
      heterogeneous photo Fenton-like reaction.

PMID- 29040934
TI  - Calibration to tool use during visually-guided reaching.
AB  - In studying human perception and performance researchers must understand how the
      body schema is modified to accurately represent one's capabilities when tools are
      used, as humans use tools that alter their capabilities frequently. The present
      work tested the idea that calibration is responsible for modifying an embodied
      action schema during tool use. We investigated calibration in the context of
      manual activity in near space through a behavioral measure. Participants made
      blind reaches to various visual distances in pre- and post-test phases using a
      short tool that did not extend their reach. During an intervening calibration
      phase they received visual feedback about the accuracy of their reaches, with
      half of the participants reaching with a tool that extended their reach by 30cm.
      Results indicated both groups showed calibration appropriate to the type of tool
      that they used during the calibration phase, and this calibration carried over to
      reaches made in the post-test. These results inform discussions on the proposed
      embodied action schema and have applications to virtual reality, specifically the
      development of self-avatars.

PMID- 29040935
TI  - Thermal stability study of crystalline and novel spray-dried amorphous nilotinib
      hydrochloride.
AB  - The thermal characteristics and the thermal degradation of crystalline and
      amorphous nilotinib hydrochloride (NH) were studied. The spray drying technique
      was successfully utilized for the amorphization of NH and was evaluated by
      spectroscopic techniques and differential scanning calorimetry (DSC). The
      ethanolic spray drying process yielded amorphous NH with a glass transition
      temperature (Tg) of 147 degrees C. Thermal characterization of the amorphous
      phase was performed by heat capacity measurements using modulated DSC (mDSC).
      Thermal degradation was studied by thermogravimetric analysis (TGA). The derived
      thermodynamic properties of the amorphous NH indicate fragile behaviour and a low
      crystallization tendency. NH was found to be molecularly stable up to 193 degrees
      C. After which, the thermal degradation displayed two phases. The values of the
      thermal degradation parameters were estimated using the Ozawa-Flynn-Wall and
      Friedman non-isothermal, model-free, isoconversional methods The results indicate
      the two phases to be single-step reactions. The examination of the physical
      stability of amorphous NH during storage and at elevated temperatures showed
      stability at 180 degrees C for at least 5h and at 20-25 degrees C/60% RH for at
      least 6 months. During these periods, no crystallization was observed. This study
      is the first to report the thermal characteristics of NH. Additionally, it is
      also the first to describe the full thermal analysis of a spray-dried amorphous
      drug. The thermal data may be used in the projection of future production
      processes and storage conditions of amorphous NH.

PMID- 29040936
TI  - Chemical profiling and quantification of Dan-Deng-Tong-Nao-capsule using ultra
      high performance liquid chromatography coupled with high resolution hybrid
      quadruple-orbitrap mass spectrometry.
AB  - Dan-Deng-Tong-Nao capsule (DDTN) was a traditional Chinese medicine (TCM)
      formula, and has been widely used for the treatment of stroke clinically which
      caused by blood stasis. However, the bioactive substances and mechanism are
      unclear because of the complex compositions in DDTN. In this research, An ultra
      high-performance liquid chromatography (UHPLC) coupled with hybrid quadruple
      orbitrap mass spectrometry (Q-Orbitrap MS) method was utilized to identify the
      chemical constituents of DDTN. In total, 102 compounds including diterpenes,
      lactones, flavonoids, and phenolic acids were identified by the accurate masses
      and fragmentation pathways, and 18 of them were unambiguously determined by
      comparison of reference standards. Besides, 12 representative compounds were
      simultaneously quantification analyzed and successfully applified for detecting
      in 9 batches of DDTN samples by UHPLC-Q-Orbitrap MS in parallel reaction
      monitoring (PRM) mode. The proposed approach was validated to be satisfied in
      terms of linearity (0.9954-0.9999), LOD (0.771ng/mL), LOQ (2.568ng/mL), intra-day
      precision ( <2.68%), inter-day precision ( <4.52%), repeatability ( <2.96%),
      stability ( <3.21%), and recovery (94.6-105.5%). The results indicate that the
      method of combining UHPLC with Q-Orbitrap MS is practical and efficient for the
      chemical clarification in DDTN, and has great potential for the integrating
      quality control of other traditional Chinese medicines.

PMID- 29040937
TI  - A sensitive HPLC-MS method for simultaneous determination of thirteen components
      in rat plasma and its application to pharmacokinetic study of Tanreqing
      injection.
AB  - A rapid, sensitive and selective method based on high-performance liquid
      chromatography coupled with Q-Exactive mass spectrometry was developed and
      validated for simultaneous quantification of thirteen components in rat plasma,
      including chlorogenic acid, 5-caffeoylquinic acid, 4-caffeoylquinic acid,
      luteoloside, isochlorogenic acid A, B and C, scutellarin, baicalin, wogonin,
      baicalein, phillyrin and forsythoside A. After precipitating proteins from the
      plasma samples with methanol, chromatographic separation of the thirteen
      components was achieved by using an XBridgeTM C18 column (2.1mm*150mm, 5MUm) with
      the mobile phase consisting of methanol and 0.1% formic acid in water at a flow
      rate of 0.3mL/min. High-resolution MS quantification was adopted with detection
      on a Q-Exactive mass spectrometer in full-scan mode, and the results were
      obtained using a mass extraction window of 10ppm at a mass resolution of 70, 000.
      All the calibration curves exhibited good linearity (r2>0.991) over the measured
      ranges. The lower limit of quantitation (LLOQ) was in the range of 1.05
      8.13ng/mL. The intra- and inter-day precision (RSD) was less than 11.70% and the
      accuracy (RE) ranged from -5.58% to 12.29%. No significant matrix effect was
      observed and the extraction recoveries of all the analytes were more than 79.36%.
      The developed method was applied to a pharmacokinetic study of the thirteen
      ingredients in rats after intravenous administration of Tanreqing at three doses
      of 3, 6 and 12mL/kg. The results indicated that 8 of the 13 components,
      isochlorogenic acid A, B and C, chlorogenic acid, baicalin, wogonin, luteoloside
      and forsythoside A, had linear pharmacokinetic properties in the tested dosage
      range.

PMID- 29040938
TI  - Age estimation using Olze's method in an adult Brazilian population.
AB  - OBJECTIVES: Age estimation is important to set an anthropological profile in
      human remains, as well as in legal issues where the suspect or victim doesn't
      have documents that prove the real age. The age estimation, in adults, is a
      challenge, and it can be analyzed through some dental stages. This study aimed to
      test Olze's method in a Brazilian sample composed by adults, aged between 20 and
      70 years old, both sex. METHODS: For experiments, 306 orthopantomography from
      Brazilian individuals between 20 and 70 years were selected. The dental
      involution through four different dental parameters were classified and the
      correlation between chronological age and the estimated age was examined by means
      of a multiple regression analysis. RESULTS: The results showed that up to 41
      years old, the correlation between real age and the interval obtained was
      considered strongly positive (R = 0.8-1), and the percentage of matching was
      78.78% for men and 71.21% for women. From 42 years old up, the correlation
      between real age and the estimation was considered null (R = 0) for both sex, and
      the percentage of matching was 17.24% for men and 6.89% for women. CONCLUSION: It
      could be concluded that the method is effective for age estimation up to 41 years
      old, but has limitations to be used over this age in Brazilian people.

PMID- 29040939
TI  - A biomimetic theranostic O2-meter for cancer targeted photodynamic therapy and
      phosphorescence imaging.
AB  - In this report, a biomimetic theranostic oxygen (O2)-meter (cancer cell
      membrane@Pt(II) porphyrinic-metal organic framework, designated as mPPt) was
      constructed for cancer targeted and phosphorescence image-guided photodynamic
      therapy (PDT). mPPt presents high photosensitizers (PSs) loading and evitable
      self-quenching behaviors for favorable biological O2 sensing and PDT. Besides,
      endowed by the surface functionalization of cancer cell membrane, the homotypic
      targeting and immune escape abilities of mPPt could dramatically enhance its
      cancer targeting ability. Importantly, the O2-dependent phosphorescence
      responsibility of mPPt could be employed to pre-evaluate the real time O2 level
      in situ and guide the PDT under light irradiation. A significant anticancer
      effect is observed after intravenous injection of mPPt and subsequent treatment
      with PDT with no obvious side effects. As a versatile platform for cell imaging,
      O2 fluctuation monitoring as well as PDT, this biomimetic O2-meter exhibits great
      potential for biological analysis and personalized cancer theranostics.

PMID- 29040940
TI  - Risk assessment and chemical fractionation of selected elements in surface
      sediments from Lake Qarun, Egypt using modified BCR technique.
AB  - In this study, spatial distribution and chemical fractionation were conducted to
      appraise the overall classification of Al, B, Cd, Cr, and Pb as well as their
      ecological risks in Lake Qarun sediments. Also, the other chemical components
      (CaCO3, TOC, SO42-, SiO32-, PO43-, F, Ca, and Mg) that represented the chemical
      composition of the sediments were determined. Modified BCR sequential extraction
      technique was used to evaluate the four (acid soluble, reducible, oxidizable and
      residual) fractions of the surface sediments. The association of Cd was found the
      highest with acid-soluble fraction (12.16-77.42%), while, Al (89.92-96.83%), B
      (42.32-93.93%), Cr (86.35-97.42%) and Pb (31.98-86.26%) were reside in residual
      phase. The degree of surface sediment contamination was computed by risk
      assessment code (RAC), individual contamination factor (ICF) and Global
      contamination factor (GCF). Risk assessment code classification showed that the
      relative amounts of easily dissolved phase of the investigated elements in the
      sediments are in the order of: Cd > Pb > B > Cr > Al. As a result, Cd had the
      highest risk to Lake Qarun. This study is a first approach of chemical
      fractionation of Al, B, Cd, Cr, and Pb in one of the most ecologically important
      Protectorates declared in the framework of Law 102 of year 1983. Information of
      this study constitutes a baseline of elements fractionation in Lake Qarun
      sediments and should be used as a reference for future studies on the changes of
      labile and residual elements fractions over time.

PMID- 29040941
TI  - Influence of arbuscular mycorrhizal fungi on antimony phyto-uptake and
      compartmentation in vegetables cultivated in urban gardens.
AB  - : 1. CONTEXT: Urban areas are often contaminated with various forms of persistent
      metal (loid) and emerging contaminants such as antimony (Sb). Thus, in the
      context of urban agriculture where sustainable practices such as biofertilizers
      application (arbuscular mycorrhizal fungi, AMF) could improve nutrient transfer
      from the soil to the vegetables, the effect of AMF on metal (loid) mobility and
      human bioaccessibility is still poorly known. 2. METHODS: The role of AMF in Sb
      uptake by lettuce and carrot grown in artificial substrate spiked with different
      Sb chemical species was investigated. Plants were grown under hydroponic
      conditions and half of the treatments received a concentrated spore solution to
      obtain mycorrhized and non-mycorrhized plants. Three weeks before harvest, plants
      were exposed to 10 mg.L-1 of either Sb2O3 or KSbO-tartrate (KSb). 3. RESULTS: The
      presence of AMF significantly increased its accumulation in carrots (all organs)
      with higher accumulation in roots. In lettuce, accumulation appeared to be
      dependent on the Sb chemical species. Moreover, it was observed for the first
      time that AMF changed the human bioaccessible fraction of Sb in edible organs. 4.
      IMPLICATIONS: The present results highlight a possible risk of Sb transfer from
      soil to edible plants cultivated in soil naturally containing AMF propagules, or
      when AMF are added as biofertilizers. After validating the influence of soil
      environment and AMF on Sb behavior in the field, these results should be
      considered in health risk assessments.

PMID- 29040942
TI  - Effects of different factors on photodefluorination of perfluorinated compounds
      by hydrated electrons in organo-montmorillonite system.
AB  - Perfluorinated compounds (PFCs) are considered as the most recalcitrant organic
      contaminants. Our previous research has shown that PFCs can be completely
      defluorinated in the UV/organoclay/3-indole acetic acid system, however, the
      factors that could affect the degradation of PFCs, are still not clear. In this
      study, we further investigated the effect of different indole derivatives and
      organo-modified montmorillonite on the degradation of perfluooctanoic acid
      (PFOA). Based on multiple linear regression analysis, our results clearly
      indicate that hydrated electron yields of indole derivatives, adsorption of PFOA
      and indole derivatives on organo-montmorillonite contributed independently to the
      degradation of PFOA. In addition, the results also show that the presence of
      humic substance (even at 10 mg C L-1) would not significantly suppress the
      degradation process due to the strong adsorption of humic substance on the organo
      montmorillonite surface. This study would provide more information to design an
      efficient and environment-friendly system for degradation of PFCs, and this
      technique will have great potential for treatment of persistent contaminants
      under mild reaction conditions.

PMID- 29040943
TI  - Liquid chromatography-tandem mass spectrometry direct injection analysis of
      organophosphorus flame retardants in Ontario surface water and wastewater
      effluent.
AB  - Organophosphorus flame retardants (OPFRs) started to be used in plastics,
      electronics and furnishings back in the 1960s and became popular again last
      decade. They are now widely present in the environment and regarded as "new"
      emerging organic pollutants. An effective liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) direct injection analysis (DIA) method was developed to
      monitor OPFR levels in aquatic environment. The removal of sample extraction and
      concentration steps not only improved operation efficiency, but also reduced the
      potential contamination commonly observed during the sample preparation process
      before. Positive background signals from the analytical instrument were
      eliminated by employing a "trap" column in front of the sample injector while an
      ACE C18 and an ACE C18-PFP column were compared for the separation of OPFRs.
      Nineteen OPFR related compounds were evaluated and rapid signal drops were
      observed for seven of them including TOTP, TMTP, TPTP, TEHP, T35DMPP, T2iPPP and
      EHDP, due to their low water solubility. The other twelve compounds, TMP, TEP,
      TPrP, TiPP, TBP, TCEP, TCPP, TDCPP, TPP, TBEP, BDCP and BEHP, were included for
      the measurement of OPFRs in drinking water, surface water, ground water and
      wastewater effluent samples. The instrumental detection limits of these twelve
      OPFRs at signal-to-noise >=3 were in the 1.5-30 ng/L range. The method was
      applied for the determination of OPFRs in surface water and wastewater samples in
      Ontario, Canada, and BEHP, TBEP, TBP, TCEP, TCPP, TDCPP, and TEP were commonly
      detected.

PMID- 29040944
TI  - Inhaled glucocorticoid treatment prevents the response of CD8+ T cells in a mouse
      model of allergic asthma and causes their depletion outside the respiratory
      system.
AB  - The principal objective of this research has been to determine the safety of
      inhaled glucocorticoids (GCs) in respect of their effect on CD8+ T cells within
      respiratory and extra-respiratory tissues, and to compare it with systemic GC
      treatment. Another purpose has been to identify whether inhaled and systemic GCs
      affect the CD8+ T cell response in the mediastinal lymph nodes (MLNs) and lungs
      in a mouse model of ovalbumin (OVA)-induced asthma. Ciclesonide and
      methylprednisolone were used as a model for inhaled and systemic GCs,
      respectively. The CD8+ T cell response was observed in untreated OVA-immunized
      mice, manifesting itself by the proliferation of these cells and their
      recruitment into the lower respiratory tract. Inhaled and systemic GC treatment
      fully prevented this response. This suggests that one of the elements
      contributing to the anti-asthmatic efficacy of inhaled and systemic GCs could be
      the inhibition of the effector CD8+ T cell response which accompanies the
      disease. The anti-asthmatic effect of GCs was rather not mediated through the
      generation or/and increased recruitment of Foxp3+CD25+CD8+ regulatory T cells
      into the MLNs and lungs. Inhaled and systemic GCs produced comparable depletions
      of normal CD8+ T cells in the MLNs, the head and neck lymph nodes and in
      peripheral blood, and this effect, at least to some extent, resulted from the
      proapoptotic action of GCs towards these cells. These results suggest that
      inhaled GC therapy might not be safer at all than treatment with systemic GCs in
      respect of the undesirable effects on CD8+ T cells residing within and outside
      the respiratory tract.

PMID- 29040945
TI  - Quercetin protects mouse liver against triptolide-induced hepatic injury by
      restoring Th17/Treg balance through Tim-3 and TLR4-MyD88-NF-kappaB pathway.
AB  - Triptolide (TP) is a diterpene triepoxide with various biological activities, but
      its clinical applications have been limited by potential hepatotoxicity, which
      can be attributed to T helper 17 (Th17)/T regulatory (Treg) cell imbalance.
      Quercetin (QE), a natural flavonoid, has been reported to have many benefits and
      medicinal properties, including hepatoprotective activity against TP-induced
      liver injury. However, the hepatoprotection mechanisms have not been clarified.
      The present study was designed to explore the protective effect and the mechanism
      of QE against TP-induced liver injury. Treatment with QE (20, 50 and 80mg/kg)
      prior to TP administration restored TP-induced alterations in a certain dose
      range indicating that QE was able to inhibit TP-induced liver injury. One
      mechanism underlying this effect was the shifting balance in Th17 and Treg cells
      from Th17 dominance to Treg dominance. Furthermore, QE markedly decreased the
      expression level of the Th17-related pro-inflammatory cytokines interleukin (IL)
      17 and IL-6, as well as the Th17 transcription factor retinoid-related orphan
      receptor-gammat (ROR-gammat). TP induced downregulation in the expression of anti
      inflammatory cytokine IL-10, but the expression of Treg transcription factor
      forkhead/winged-helix family transcriptional repressor p3 (FoxP3) was restored by
      QE. In the process of exploring the possible hepatoprotective mechanisms of QE,
      we found that QE significantly reduced both protein and mRNA expression of Toll
      like receptor 4 (TLR4), which in turn not only inactivated myeloid
      differentiation primary response gene 88 (MYD88), nuclear factor kappa B (NF
      kappaB) and related inflammatory cytokines IL-6 and IL-17, but also
      simultaneously increased the levels of T-cell immunoglobulin and mucin domain
      containing protein 3 (Tim-3). Furthermore, blocking of TLR4 enhanced the effect
      of QE in regulating the Th17/Treg imbalance. In summary, this report has
      demonstrated for the first time that the protection afforded by QE against TP
      induced liver injury was associated with a shift in the balance of Th17 and Treg
      cells to Treg dominance, which was regulated by Tim-3 and TLR4-MyD88-NF-kappaB
      signaling pathway.

PMID- 29040946
TI  - Neuropsychological predictors of response to cognitive behavioral therapy for
      posttraumatic stress disorder in persons with severe mental illness.
AB  - This study examined whether cognitive functioning was related to treatment
      outcomes in persons with severe mental illness who received a cognitive
      behavioral therapy (CBT) program for co-occurring posttraumatic stress disorder
      (PTSD). The study sample was drawn from a larger controlled trial of 108 persons
      with severe mental illness and PTSD comparing the effects of CBT with treatment
      as usual on PTSD and related outcomes, with assessments conducted at baseline,
      post-treatment, and 3- and 6-month follow-ups. Among the 54 persons in CBT, 49
      were administered a neuropsychological battery at baseline and 40 were exposed to
      the CBT program. Statistical analyses of these 40 participants were conducted to
      evaluate whether cognitive functioning was related to participation in the CBT
      program, completion of homework assignments, and improvements in PTSD, and other
      outcomes. Cognitive functioning was not related to participation in CBT or
      completion of homework. Lower cognitive functioning predicted less learning of
      information about PTSD at post-treatment and follow-up, but not less clinical
      benefit from CBT in PTSD diagnosis or symptoms, other symptoms, or health. The
      results suggest that cognitive impairment does not attenuate response to the CBT
      for PTSD program in persons with severe mental illness. Clinical Trials.gov
      Identifier: NCT00053690.

PMID- 29040947
TI  - A 6-week, multicenter, double-blind, double-dummy, chlorpromazine-controlled non
      inferiorityrandomized phase iiitrial to evaluate the efficacy and safety of
      quetiapine fumarate (SEROQUEL) extended-release (XR) in the treatment of patients
      with schizophrenia and acute episodes.
AB  - This study aimed to evaluate the efficacy and safety of quetiapine fumarate
      extended-release (XR) in the treatment of Chinese patients with acute
      schizophrenia. Multicenter, double-blind, double-dummy, active-controlled non
      inferiority randomized study in Chinese patients (n = 388) with schizophrenia
      randomly assigned to quetiapine XR or chlorpromazine for 6 weeks. Primary outcome
      was the change from baseline in Positive and Negative Syndrome Scale (PANSS)
      total score at the end of treatment. Safety objectives included adverse event
      (AE) monitoring, laboratory test results, and electrocardiograms. Changes in
      PANSS total score were -33.4 for quetiapine XR and -35.9 for chlorpromazine (P >
      0.05). Least squares mean changes were: positive subscale, -9.9 +/- 0.53 and 
      11.1 +/- 0.51; negative subscale, -5.9 +/- 0.50 and -6.7 +/- 0.48; general
      psychopathology subscale, -12.9 +/- 0.74 and -13.9 +/- 0.71; aggression and
      hostility cluster scores, -4.8 +/- 0.33 and -5.4 +/- 0.32; and depression cluster
      scores, -1.8 +/- 0.18 and -1.7 +/- 0.18, for quetiapine XR and chlorpromazine,
      respectively. For quetiapine XR, AEs were constipation, dizziness, insomnia, and
      agitation, and nine patients (4.6%) discontinued due to AEs. For chlorpromazine,
      AEs were extrapyramidal symptoms, constipation, insomnia, dizziness, and
      agitation, and 17 patients (8.9%) discontinued due to AEs; two patients reported
      serious AEs. Quetiapine XR monotherapy was not inferior to chlorpromazine for
      treating acute schizophrenia in Chinese patients and was well tolerated.

PMID- 29040948
TI  - A prospective cohort study of community functioning among psychiatric
      outpatients.
AB  - The present study analyzed the community functioning among Chinese people with
      common mental disorders and their relationships with different factors under the
      framework of Model of Human Occupation. The research team followed up a
      stratified random sample of 238 patients in three public psychiatric specialist
      outpatient clinics in Hong Kong in one year. The patients completed assessments
      at baseline and 12-month follow-up in four areas of community functioning (i.e.,
      self-care, independent living skills, social skills, and work skills), self
      esteem, self-efficacy, physical functioning, behavioral regulation, mental
      states, family expressed emotion, and perceived social stigma. The data showed
      that after 12 months, the patients had positive changes in self-care, work
      skills, and behavioral regulation. Those patients who had higher levels of self
      esteem at baseline and reduced their negative reactions to stigma were more
      likely to improve social skills, while those patients who perceived less
      discrimination at baseline and enhanced their self-esteem would have a higher
      likelihood of making improvement in work skills. The findings implied that the
      rehabilitation services for people with common mental disorders might target on
      the enhancement of self-esteem and reduction of discrimination experience to
      facilitate their improvement in social skills and work skills.

PMID- 29040949
TI  - Phenomenological characteristics of recovered memory in nonclinical individuals.
AB  - A central hypothesis of recovered memory is that the source of the memory may be
      misattributed, and the memory of an imagined event may be mistaken as the memory
      of the perceived event that was not remembered. The judgment of memory source
      depends upon phenomenological characteristics. Thus, the present study
      investigated characteristics of recovered memory. To exclude potential
      confounding effects of traumatic stress and acute mental illness, data on
      recovered memories of diverse valences in a nonclinical sample were collected.
      Self-report scales including a measure of memory characteristics were used to
      evaluate recovered memories and age-matched autobiographical memories that had
      been continuously remembered. The results showed that recovered memory was of
      lower clarity and contained less detailed sensory, contextual, and temporal
      information; additionally, it was associated with fewer thoughts and lower
      intensity of feelings. Participants also felt less confident regarding the
      veracity of recovered memory in comparison with continuous memory. In contrast to
      recovered trauma memory reported by clinical clients, vivid sensory details and
      intense affect did not characterize recovered memory in nonclinical individuals.
      The reduction in perceptual and contextual information, as well as cognitive
      operations, may increase the difficulty of judging the source of recovered
      memory.

PMID- 29040950
TI  - Green spaces are not all the same for the provision of air purification and
      climate regulation services: The case of urban parks.
AB  - The growing human population concentrated in urban areas lead to the increase of
      road traffic and artificial areas, consequently enhancing air pollution and urban
      heat island effects, among others. These environmental changes affect citizen's
      health, causing a high number of premature deaths, with considerable social and
      economic costs. Nature-based solutions are essential to ameliorate those impacts
      in urban areas. While the mere presence of urban green spaces is pointed as an
      overarching solution, the relative importance of specific vegetation structure,
      composition and management to improve the ecosystem services of air purification
      and climate regulation are overlooked. This avoids the establishment of optimized
      planning and management procedures for urban green spaces with high spatial
      resolution and detail. Our aim was to understand the relative contribution of
      vegetation structure, composition and management for the provision of ecosystem
      services of air purification and climate regulation in urban green spaces, in
      particular the case of urban parks. This work was done in a large urban park with
      different types of vegetation surrounded by urban areas. As indicators of
      microclimatic effects and of air pollution levels we selected different metrics:
      lichen diversity and pollutants accumulation in lichens. Among lichen diversity,
      functional traits related to nutrient and water requirements were used as
      surrogates of the capacity of vegetation to filter air pollution and to regulate
      climate, and provide air purification and climate regulation ecosystem services,
      respectively. This was also obtained with very high spatial resolution which
      allows detailed spatial planning for optimization of ecosystem services. We found
      that vegetation type characterized by a more complex structure (trees, shrubs and
      herbaceous layers) and by the absence of management (pruning, irrigation and
      fertilization) had a higher capacity to provide the ecosystems services of air
      purification and climate regulation. By contrast, lawns, which have a less
      complex structure and are highly managed, were associated to a lower capacity to
      provide these services. Tree plantations showed an intermediate effect between
      the other two types of vegetation. Thus, vegetation structure, composition and
      management are important to optimize green spaces capacity to purify air and
      regulate climate. Taking this into account green spaces can be managed at high
      spatial resolutions to optimize these ecosystem services in urban areas and
      contribute to improve human well-being.

PMID- 29040951
TI  - Perfluoroalkyl substances, bone density, and cardio-metabolic risk factors in
      obese 8-12 year old children: A pilot study.
AB  - BACKGROUND AND OBJECTIVE: Perfluoroalkyl substances (PFASs), including
      perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS),
      perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), have
      been associated with adverse bone, and metabolic changes in adults. However
      association of PFASs with bone health in children is understudied. Considering
      their role as endocrine disruptors, we examined relationships of four PFASs with
      bone health in children. METHODS: In a cross sectional pilot study, 48 obese
      children aged 8-12 years were enrolled from Dayton's Children Hospital, Ohio.
      Anthropometric, clinical and biochemical assessments of serum were completed.
      Serum PFASs were measured by UPLC-ESI-MS/MS. In a subset of 23 children, bone
      health parameters were measured using calcaneal quantitative ultrasound (QUS).
      RESULTS: While PFASs exposure was associated with a consistent negative
      relationship with bone health parameters, among four PFASs tested, only PFNA
      showed a significant negative relationship with bone parameter (beta [95% CI], = 
      72.7 [- 126.0, - 19.6], p = .010). PFNA was also associated with raised systolic
      blood pressure (p = .008), low density lipoprotein cholesterol (LDL-C; p < .001),
      and total cholesterol (TC; p = .014). In addition, both PFOA and PFOS predicted
      elevation in LDL-C, and PFOA predicted increased TC, as well. In this analysis,
      PFASs were not strongly related to thyroid hormones, 25-hydroxy vitamin D, liver
      enzymes, or glucose homeostasis. CONCLUSION: PFASs exposure in obese children may
      play a role in adverse skeletal and cardiovascular risk profiles.

PMID- 29040952
TI  - Design, synthesis, kinetic mechanism and molecular docking studies of novel 1
      pentanoyl-3-arylthioureas as inhibitors of mushroom tyrosinase and free radical
      scavengers.
AB  - A series of novel 1-pentanoyl-3-arylthioureas was designed as new mushroom
      tyrosinase inhibitors and free radical scavengers. The title compounds were
      obtained in excellent yield and characterized by FTIR, 1H NMR, 13C NMR and X-ray
      crystallography in case of compound (4a). The inhibitory effects on mushroom
      tyrosinase and DPPH were evaluated and it was observed that 1-Pentanoyl-3-(4
      methoxyphenyl) thiourea (4f) showed tyrosinase inhibitory activity (IC50 1.568 +/
      0.01 mM) comparable to Kojic acid (IC50 16.051 +/- 1.27 mM). Interestingly
      compound 4f exhibited higher antioxidant potential compared to other derivatives.
      The docking studies of synthesized 1-Pentanoyl-3-arylthioureas analogues were
      also carried out against tyrosinase protein (PDBID 2ZMX) to compare the binding
      affinities with IC50 values. The predicted binding affinities are in good
      agreement with the IC50 values as compound (4f) showed highest binding affinity (
      7.50 kcal/mol) compared to others derivatives. The kinetic mechanism analyzed by
      Line-weavere Burk plots exhibited that compound (4f) inhibit the enzyme inhibits
      the tyrosinase non-competitively to form an enzyme inhibitor complex. The
      inhibition constants Ki calculated from Dixon plots for compound (4f) is 1.10
      MUM. It was also found from kinetic analysis that derivative 4f irreversible
      enzyme inhibitor complex. It is proposed on the basis of our investigation that
      title compound (4f) may serve as lead structure for the design of more potent
      tyrosinase inhibitors.

PMID- 29040953
TI  - Design, synthesis and biological evaluation of novel alpha-hederagenin
      derivatives with anticancer activity.
AB  - In an attempt to arrive at a more potent cytotoxic agent than the parent compound
      alpha-hederagenin (H), 24 alpha-hederagenin derivatives (5-8, 11-24, 27-28, 31
      32, and 35-36) were synthesized in a concise and efficient strategy and screened
      for in vitro cytotoxicity against the human cancer cell lines MKN45 and KB. Among
      these compounds, the polyamine derivative 15 exhibited more potency than the
      parent compound with IC50 values in the range of 4.22 MUM-8.05 MUM. Compound 15
      increased Bax/bcl-2 ratio that disrupted the mitochondrial potential and induced
      apoptosis. Therefore, the present studies highlight the importance of polyamine
      derivatives of alpha-hederagenin in the discovery and development of novel
      anticancer agents.

PMID- 29040954
TI  - Design, synthesis and biological evaluation of substituted aminopyridazin-3(2H)
      ones as G0/G1-phase arresting agents with apoptosis-inducing activities.
AB  - A series of aminopyridazin-3(2H)-one derivatives has been designed and
      synthesized. Their antiproliferative activities were evaluated against three
      human cancer cell lines (SH-SY5Y human neuroblastoma, K562 human myelogenous
      leukemia and AGS gastric cancer cell lines) using the MTT assay. The preliminary
      activity test displayed that compound 8a exhibited comparable activities against
      all test cells with the positive control fluorouracil. Meanwhile compounds 8b, 8e
      and 9c-e displayed selective antiproliferative activities for SH-SY5Y cells.
      Furthermore, compounds 8a-b with low-micromole GI50 value for SH-SY5Y cells
      induced apoptosis with cell cycle arrest at G0/G1 phase in SH-SY5Y cells in a
      dose-dependent manner.

PMID- 29040955
TI  - Protective role of epigallocatechin-3-gallate on arsenic induced testicular
      toxicity in Swiss albino mice.
AB  - Arsenic, often referred to as the king of poisons is carcinogenic in humans and
      animals. It affects multiorgan systems including reproduction. The present study
      was undertaken to explore the protective role of green tea compound,
      epigallocatechin-3-gallate (EGCG) on arsenic induced testicular toxicity in Swiss
      albino mice. Thirty two adult male mice were randomly assigned to four groups
      (n=8). Group I served as control without test chemical. The group II received
      arsenic (200ppm) through drinking water, group III received only EGCG
      (20mg/kgb.wt., intraperitoneally, alternate days) and group IV was administered
      arsenic+EGCG for 40days. Factorial experimental design was employed to assess the
      treatment effect. The EGCG restored arsenic induced decrements in epididymal
      sperm concentration, kinematic attributes (total motility, rapid, progressive
      motile, fast progressive, VSL, VAP, VCL, BCF, LIN, WOB, STR and Type A),
      structutal membrane integrity, functional membrane integrity and mitochondrial
      membrane potential. As evidenced by the histoarchitectural studies, the EGCG
      reversed the deleterious effects of arsenic on testicular malondialdehyde
      (p<0.05) levels, reduced glutathione, antioxidative enzymes and spermatogenesis.
      Overall, the results suggest that EGCG reduces the testicular oxidative stress
      induced by arsenic poisoning and thereby protect the reproductive system.

PMID- 29040956
TI  - Antihyperlipidemic effect of Pistacia khinjuk.
AB  - BACKGROUND: Hyperlipidemia is a metabolic disorder that is caused by high levels
      of triglycerides and cholesterol in blood. Using of plants for the treatment of
      various ailments is a traditional practice in developing countries. The main
      objective of the study is to analyse the nutritional composition of Pistacia
      khinjuk and to assess its anti-hyperlipidemic activity. MATERIALS AND METHODS: In
      the present study, the ethanolic extract of Pistacia khinjuk leaves was evaluated
      for antihyperlipidemic activity. 40 adult albino rats were divided into five
      groups. Hyperlipidemia was induced using high fat diet for 60days. Pistacia
      khinjuk extract of 150mg/kg body weight and 300mg/kg of body weight was
      administered to the rats for 28days. Proximate analysis of Pistacia khinjuk was
      also performed. RESULTS: Proximate analysis of Pistacia khinjuk leaves showed
      6.8% ash content, 12.8% crude fiber and only 6.85% fat content. Findings of
      present study revealed that both doses of Pistacia khinjuk extract improved the
      serum lipid profile in albino rats by reducing total lipids, total cholesterol,
      triglycerides and low density lipoprotein, and increasing high density
      lipoprotein levels in Pistacia khinjuk treated groups. Body weight findings
      showed significant increase in body weight of all groups from zero day to 60th
      day. But before sacrifice, there was a decrease in hyperlipidemic and high dose
      Pistacia khinjuk while increase in control and low dose Pistacia khinjuk group
      respectively. CONCLUSION: From the results of the present study, it is concluded
      that Pistacia khinjuk extract has curative effect against hyperlipidemia.

PMID- 29040957
TI  - Molecular docking and antiamnesic effects of nepitrin isolated from Rosmarinus
      officinalis on scopolamine-induced memory impairment in mice.
AB  - Rosmarinus officinalis has long been known as the herb of remembrance. The
      present study was undertaken to investigate the anti-amnesic effects of nepitrin
      isolated from Rosmarinus officinalis using in-vivo models of Y-maze and novel
      object recognition test (NORT) along with in vitro antioxidant and
      acetylcholinesterase (AChE) and buterylcholinesterase (BuChE) inhibition
      potential. Nepitrin showed a concentration dependent inhibition of AChE and BuChE
      enzymes with IC50 values of 65 and 72MUg/mL, respectively and antioxidant
      activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2'-azinobis-3
      ethylbenzothiazoline-6-sulfonic acid (ABTS) with IC50 values 270 and 210MUg/mL,
      respectively. In mice, nepitrin reversed the amnesia induced by scopolamine as
      indicated by a dose-dependent increase in spontaneous alternation performance in
      the Y-maze task (p <0.05 versus scopolamine) and increase in the discrimination
      index in the novel object recognition test (NORT) comparable to the standard drug
      donepezil 2mg/kg. Molecular docking studies were performed and the GlideScore of
      nepitrin was consistent with its experimental AChE inhibitory activities.
      Nepitrin occupied the same binding site forming similar interactions to those
      formed by donepezil in the crystal structure. Thus, nepitrin could provide a lead
      for the development of therapeutic agent useful in cognition and memory disorders
      such as Alzheimer's disease.

PMID- 29040958
TI  - The potential protective role of Akropower against Atrazine- induced humoral
      immunotoxicity in rabbits.
AB  - Introduction to the herbicide Atrazine (ATR) can bring about immunotoxicity,
      aside from other unfavorable results for the creature and human wellbeing. We
      went for clarifying the genotoxic mechanisms required in humoral immunotoxicity
      of Gesaprim(r) (ATR) and their constriction by Akropwer. Forty rabbits (1.5kg+/
      20%) were utilized and appointed into 4 equal groups. group 1: control; group 2:
      Received Atrazine at 1/10 LD50 via food; group 3: Received Akropwer at 1ml/1l/day
      by means of drinking water; group 4: Received both Atrazine and Akropwer
      associatively by the same said dosage and course. Atrazine and Akropower exposure
      were accomplished for 60days. The genotoxic mechanisms of Atrazine- induced
      humoral immunotoxicity were explained by increased serum total protein and
      albumin levels, decreased RHDV antibody titer only after four weeks of
      vaccination and increased level of spleen Fas and Caspase-III genes expression in
      Atrazine-exposed rabbits. Marked splenocytes apoptosis were detected in the
      immunohistochemical examination by caspase-III technique and TUNEL assay.
      Akropower attenuated ATR-induced apoptosis through down-regulation of Fas and
      Caspase-III genes expression and suppression of their signaling pathway. In
      conclusion, induction of apoptosis by overexpression of Fas and Caspase-III genes
      gives a new insight into the mechanism of ATR immunotoxicity. The protective part
      of Akropower, on the other hand, was characterized by attenuation of Fas and
      Caspase-III genes mediated apoptosis.

PMID- 29040959
TI  - Marantodes pumilum (Kacip fatimah) enhances in-vitro glucose uptake in 3T3-L1
      adipocyte cells and reduces pancreatic complications in streptozotocin
      nicotinamide induced male diabetic rats.
AB  - : Marontades pumilum is claimed to have beneficial effects in the treatment of
      diabetes mellitus (DM), however the underlying mechanisms were not fully
      identified. In this study, we hypothesized that M. pumilum could help to enhance
      cellular glucose uptake and reduces pancreatic complications, which contributed
      towards its beneficial effects in DM. METHODS: Two parameters were measured (i)
      rate of glucose uptake by 3T3-L1 adipocyte cells in-vitro (ii) degree of
      pancreatic destruction in streptozotocin-nicotinamide induced male diabetic rats
      receiving M. pumilum aqueous extract (M.P) (250 and 500mg/kg/day) as reflected by
      levels of pancreatic oxidative stress, inflammation and apoptosis. In the
      meantime, phyto-chemical compounds in M.P were also identified by using LC-MS.
      RESULTS: M.P was found able to enhance glucose uptake by 3T3-L1 adipocyte cells
      in-vitro while its administration to the male diabetic rats causes decreased in
      the fasting blood glucose (FBG), glycated haemoglobin (HbA1c), total cholesterol
      (TC), triglycerides (TG), low-density lipoprotein (LDL) levels but causes
      increased in insulin and high-density lipoprotein (HDL) levels, to near normal.
      Levels of oxidative stress in the pancreas as reflected by levels of lipid
      peroxidation product (LPO) decreased while levels of anti-oxidantive enzymes
      (SOD, CAT and GPx) in pancreas increased. Additionally, levels of inflammation as
      reflected by NF-kappaB p65, Ikkbeta and TNF-alpha levels decreased while
      apoptosis levels as reflected by caspase-9 and Bax levels decreased. Anti
      apoptosis marker, Bcl-2 levels in pancreas increased. CONCLUSIONS: The ability of
      M.P to enhance glucose uptake and reduces pancreatic complications could account
      for its beneficial effects in treating DM.

PMID- 29040960
TI  - A novel S-sulfhydrated human serum albumin preparation suppresses melanin
      synthesis.
AB  - Products of ultraviolet (UV) irradiation such as reactive oxygen species (ROS)
      and nitric oxide (NO) stimulate melanin synthesis. Reactive sulfur species (RSS)
      have been shown to have strong ROS and NO scavenging effects. However, the
      instability and low retention of RSS limit their use as inhibitors of melanin
      synthesis. The free thiol at Cys34 on human serum albumin (HSA) is highly stable,
      has a long retention and possess a high reactivity for RSS. We report herein on
      the development of an HSA based RSS delivery system. Sulfane sulfur derivatives
      released from sodium polysulfides (Na2Sn) react readily with HSA. An assay for
      estimating the elimination of sulfide from polysulfide showed that almost all of
      the sulfur released from Na2Sn bound to HSA. The Na2Sn-treated HSA was found to
      efficiently scavenge ROS and NO produced from chemical reagents. The Na2Sn
      treated HSA was also found to inhibit melanin synthesis in B16 melanoma cells and
      this inhibition was independent of the number of added sulfur atoms. In B16
      melanoma cells, the Na2Sn-treated HSA also inhibited the levels of ROS and NO
      induced by UV radiation. Finally, the Na2Sn-treated HSA inhibited melanin
      synthesis from L-DOPA and mushroom tyrosinase and suppressed the extent of
      aggregation of melanin pigments. These data suggest that Na2Sn-treated HSA
      inhibits tyrosinase activity for melanin synthesis via two pathways; by directly
      inhibiting ROS signaling and by scavenging NO. These findings indicate that Na2Sn
      treated HSA has potential to be an attractive and effective candidate for use as
      a skin whitening agent.

PMID- 29040961
TI  - Effect of double-layer application on bond quality of adhesive systems.
AB  - OBJECTIVES: The aim of this study was to determine the effect of double-layer
      application of universal adhesives on the bond quality and compare to other
      adhesive systems. METHODS: Two universal adhesives used were in this study:
      Scotchbond Universal (SU), [3M ESPE] and Prime & Bond elect (PE), [Dentsply
      Caulk]. The conventional single-step self-etch adhesives G-aenial Bond (GB), [GC
      Corporation.] and BeautiBond (BB), [Shofu Inc.], and a two-step self-etch
      adhesive, Optibond XTR (OX), [Kerr Corporation], were used as comparison
      adhesives. Shear bond strengths (SBS) and shear fatigue strengths (SFS) to human
      enamel and dentin were measured in single application mode and double application
      mode. For each test condition, 15 specimens were prepared for SBS testing and 30
      specimens for SFS testing. RESULTS: Enamel and dentin SBS of the universal
      adhesives in the double application mode were significantly higher than those of
      the single application mode. In addition, the universal adhesives in the double
      application mode had significantly higher dentin SFS values than those of the
      single application mode. The two-step self-etch adhesive OX tended to have lower
      bond strengths in the double application mode, regardless of the test method or
      adherent substrate. CONCLUSION: The double application mode is effective in
      enhancing SBS and SFS of universal adhesives, but not conventional two-step self
      etch adhesives. SIGNIFICANCE: These results suggest that, although the double
      application mode may enhance the bonding quality of a universal adhesive, it may
      be counter-productive for two-step self-etch adhesives in clinical use.

PMID- 29040962
TI  - Interactions between rGO/TNT nanocomposites and cells: Regulation of cell
      morphology, uptake, cytotoxicity, adhesion and migration.
AB  - Reduced graphene oxide/titanium dioxide nanotube (rGO/TNT) composites have
      superior properties, such as a large surface area, extraordinary mechanical
      strength, high carrier mobility, etc. However, the biosafety and biocompatibility
      of these composites, such as their influences on cell viability and cell
      functions, which are of paramount importance, are still not fully addressed. In
      this study, rGO/TNT nanocomposites were successfully synthesized through a
      modified hydrothermal treatment method. Then, the interactions between the
      rGO/TNT nanocomposites and Raw264.7 mouse monocyte-macrophage cells were further
      investigated. The results show that the rGO/TNT nanocomposites could be
      internalized by Raw264.7 cells and mainly gathered inside the cytoplasm. No
      rGO/TNT nanocomposites were observed in the nucleus. Moreover, the rGO/TNT
      nanocomposites exhibited low cytotoxicity toward Raw264.7 cells at a lower dose,
      though they may exhibit cytotoxicity to some extent at very high concentrations.
      In addition, the uptake of the nanocomposites influenced the cell cytoskeleton
      organization, while the cell adhesion and migration abilities were also impaired.

PMID- 29040963
TI  - New adhesive system based in metals cross-linking methacrylate.
AB  - This study evaluated the anti-antibiofilm potential of silver methacrylate (Ag)
      or di-n-butyldimethacrylatetin (Sn) in experimental adhesive systems. Ag and Sn
      methacrylates were incorporated at 0.5mol%, 1mol% and 2mol% in an adhesive resin.
      The anti-antibiofilm potential, degree of conversion (DC), microtensile bond
      strength (MUTBS), water sorption/solubility (WSR/SL), bonded interfaces pattern
      (SEM), cytotoxicity and leaching of Ag and Sn ions were evaluated. Data were
      statistically analyzed considering alpha = 0.05. Only Ag at 2% affected DC and
      MUTBS. Ag at 1% and 2% and Sn at 1% and 2% showed anti-biofilm potential against
      Mutans streptococci. Ag at 1% and 2% and Sn at 2% showed a statistically
      significant difference to the control in WSR/SL (p < 0.05). The additions of
      metal methacrylate did not affect cell viability, being the adhesive resins
      statistically similar to controls. Leached metals of Ag were more than 100x
      higher than for Sn. Between the concentration tested, Ag and Sn methacrylate at
      1% presented an anti-biofilm effect without altering the mechanical properties
      evaluated.

PMID- 29040964
TI  - Polymorphisms in adrenergic receptor genes in Qinchuan cattle show associations
      with selected carcass traits.
AB  - The beta-adrenergic receptors coded by the ADRB1, ADRB2 and ADRB3 genes play
      important roles in mediating metabolic effects, especially lipolysis, insulin
      resistance and energy balance. This study investigated the expression levels of
      these three genes in different tissues of Qinchuan cattle by real-time polymerase
      chain reaction (RT-PCR). Expressed levels of RNA from the ADRB2 gene were
      generally much higher than for ADRB1 and ADRB3. ADRB1 and ADRB2 expression levels
      were highest in subcutaneous fat and lower in muscle, whereas ADRB3 expression
      was higher in muscle tissue. Eight single nucleotide polymorphisms (SNPs) were
      discovered in 503 Qinchuan cattle by DNA sequencing, containing three missense
      mutations (g.1148G>C in ADRB1, g.1293C>T and g.1311T>C in ADRB2), four synonymous
      mutations (g.1054T>C, g.1122C>T and g.1143G>T in ADRB1 and g.506A>G in ADRB3), as
      well as one mutation in 3'untranslated region (3'UTR) (g.2799G>A in ADRB3).
      Interestingly, five of them were located in regions predicted to contain multiple
      repeats of CG nucleotides (CpG islands). Association analysis showed
      relationships between most of those SNPs or combined haplotypes and carcass
      traits of Qinchuan cattle. This study association analysis suggests that
      polymorphisms in these genes might be useful for selection in beef cattle
      breeding.

PMID- 29040965
TI  - Distribution of cancer mortality rates by province in South Africa.
AB  - INTRODUCTION: Cancer mortality rates are expected to increase in developing
      countries. Cancer mortality rates by province remain largely unreported in South
      Africa. This study described the 2014 age standardised cancer mortality rates by
      province in South Africa, to provide insight for strategic interventions and
      advocacy. METHODS: 2014 deaths data were retrieved from Statistics South Africa.
      Deaths from cancer were extracted using 10th International Classification of
      Diseases (ICD) codes for cancer (C00-C97). Adjusted 2013 mid-year population
      estimates were used as a standard population. All rates were calculated per 100
      000 individuals. RESULTS: Nearly 38 000 (8%) of the total deaths in South Africa
      in 2014 were attributed to cancer. Western Cape Province had the highest age
      standardised cancer mortality rate in South Africa (118, 95% CI: 115-121 deaths
      per 100 000 individuals), followed by the Northern Cape (113, 95% CI: 107-119 per
      100 000 individuals), with the lowest rate in Limpopo Province (47, 95% CI: 45-49
      per 100 000). The age standardised cancer mortality rate for men (71, 95% CI: 70
      72 per 100 000 individuals) was similar to women (69, 95% CI: 68-70 per 100 000).
      Lung cancer was a major driver of cancer death in men (13, 95% CI: 12.6-13.4 per
      100 000). In women, cervical cancer was the leading cause of cancer death (13,
      95% CI: 12.6-13.4 per 100 000 individuals). CONCLUSION: There is a need to
      further investigate the factors related to the differences in cancer mortality by
      province in South Africa. Raising awareness of risk factors and screening for
      cancer in the population along with improved access and quality of health care
      are also important.

PMID- 29040966
TI  - Natural product celastrol suppressed macrophage M1 polarization against
      inflammation in diet-induced obese mice via regulating Nrf2/HO-1, MAP kinase and
      NF-kappaB pathways.
AB  - Macrophage polarization is implicated in the inflammation in obesity. The aim of
      the present study was to examine the anti-inflammatory activities of botanical
      triterpene celastrol against diet-induced obesity. We treated diet-induced obese
      C57BL/6N male mice with celastrol (5, 7.5 mg/kg/d) for 3 weeks, and investigated
      macrophage M1/M2 polarization in adipose and hepatic tissues. Celastrol reduced
      fat accumulation and ameliorated glucose tolerance and insulin sensitivity.
      Celastrol down-regulated the mRNA levels of macrophage M1 biomarkers (e.g., IL-6,
      IL-1beta, TNF-alpha, iNOS) in cell culture and in mice. The underlying mechanisms
      were investigated in murine macrophage RAW264.7 cells. Our results demonstrated
      that celastrol might control macrophage polarization through modulating the cross
      talk between the following three mechanisms: 1) suppressing LPS-induced
      activation of MAP kinases (e.g., ERK1/2, p38, JNK) in a concentration dependent
      manner; 2) attenuating LPS-induced nuclear translocation of NF-kappaB p65 subunit
      in a time dependent manner; 3) activating Nrf2 and subsequently inducing HO-1
      expression. HO-1 inhibitor SnPP diminished the inhibitory effects of celastrol on
      the activation of NF-kappaB pathway and the pro-inflammatory M1 macrophage
      polarization. Taken together, celastrol exhibited anti-obesity effects via
      suppressing pro-inflammatory M1 macrophage polarization. Thus, our results
      provide new evidence for the potential of celastrol in the treatment of obesity.

PMID- 29040967
TI  - Improvement and Aggravation of Spontaneous Unruptured Vertebral Artery
      Dissection.
AB  - BACKGROUND: Intracranial vertebral artery dissection (VAD) is a well-recognized
      cause of stroke in young and middle-aged individuals, especially in Asian
      populations. However, a long-term natural course remains unclear. We investigated
      the long-term time course of VAD using imaging findings to examine the rate and
      predisposing factors for improvement. METHODS: We registered 56 consecutive
      patients (40 males; mean age, 51.8 +/- 10.7 years) with acute spontaneous VAD and
      retrospectively investigated neuroimaging and clinical course within 1 month and
      at 3 months +/- 2 weeks, 6 months +/- 2 weeks, and 12 months +/- 2 weeks after
      onset to ascertain predisposing factors and time course for improvement. RESULTS:
      The most common presenting symptoms were headache and/or posterior neck pain,
      seen in 41 patients (73%). Magnetic resonance imaging showed brainstem and/or
      cerebellum infarction in only 32 patients (57%). Of the 56 VADs, 16 (28%)
      presented with pearl and string sign, 5 (9%) with pearl sign, 15 (27%) with
      string sign, and 20 (36%) with occlusion sign. VAD occurred on the dominant side
      in 20 patients and on the nondominant side in the other 36 patients. The pearl
      and string sign was more frequently noted on the dominant side than on the
      nondominant side (50 vs. 17%, p = 0.008). On the other hand, occlusion occurred
      more often on the nondominant side than on the dominant side (47 vs. 15%, p =
      0.016). Furthermore, the pearl and string sign was more frequently seen in the
      improvement group (41 vs. 15%, p = 0.028), whereas the occlusion sign was evident
      more frequently in the nonimprovement group (21 vs. 52%, p = 0.015). Follow-up
      neuroimaging evaluation was performed at 1 and 3 months in 91% each, and at 6 and
      12 months in 82% each. VAD aggravation was identified within 1 month after onset
      in 14%, while VAD improvement was seen in 14, 38, 50, and 52% at each period,
      mainly within 6 months after onset. Older patients and current smoking were
      negatively associated with VAD improvement. CONCLUSIONS: VAD improvement
      primarily occurs within 6 months after onset, and VAD aggravation within 1 month.
      It seems that older patients and current smoking are negative predictors of VAD
      improvement as risk factors, and as image findings, the pearl and string sign is
      a positive predictor and occlusion a negative predictor.

PMID- 29040968
TI  - Neutrophils Kill Reactive Oxygen Species-Resistant Pseudomonas aeruginosa by
      Sphingosine.
AB  - BACKGROUND/AIMS: Cystic fibrosis (CF) is dominated by chronic inflammation and
      infection of the lung resulting in lung destruction and early death of patients.
      The lungs of CF patients are characterized by a massive accumulation of
      neutrophils. It requires definition why these massive numbers of neutrophils fail
      to eliminate typical CF pathogens like Staphylococcus aureus and Pseudomonas
      aeruginosa (P. aeruginosa) in CF lungs. METHODS: We determined ceramide,
      sphingosine and reactive oxygen species (ROS) in neutrophils from wildtype and CF
      mice and determined the effect of sphingosine and ROS alone or in combination on
      killing of different P. aeruginosa strains. RESULTS: We demonstrate that wildtype
      neutrophils are able to kill non-mucoid and mucoid clinical P. aeruginosa
      strains, while neutrophils from CF mice are insufficient to kill these P.
      aeruginosa strains, although both types of neutrophils infected with P.
      aeruginosa produce comparable levels of superoxide. All three analyzed P.
      aeruginosa strains are resistant to reactive oxygen species. The inability of CF
      neutrophils to kill P. aeruginosa is caused by a marked decrease of surface
      sphingosine levels in CF neutrophils. Wildtype neutrophils contain much higher
      concentrations of surface sphingosine than CF neutrophils. Further, wildtype
      neutrophils, but not CF neutrophils, release sphingosine, most likely as
      microparticles, upon infection. Sphingosine kills P. aeruginosa in vitro at low
      micromolar concentrations. Reconstitution of sphingosine in CF neutrophils
      restores their ability to kill these pathogens, demonstrating the significance of
      sphingosine for bacterial killing. CONCLUSION: The data provide evidence for a
      new paradigm explaining how neutrophils kill ROS-resistant P. aeruginosa, i.e. by
      sphingosine that kills P. aeruginosa at low concentrations. This mechanism is
      defective in CF neutrophils.

PMID- 29040969
TI  - Comparison of IGH Profile Signals Using t(4;14) and IGH Break-Apart Probes by
      FISH in Multiple Myeloma.
AB  - We compared immunoglobulin heavy chain gene (IGH) signal patterns in multiple
      myeloma (MM) using the FGFR3-IGH and the IGH break-apart probes to facilitate
      their understanding and analysis. Forty-nine patients with MM were studied. FISH
      was performed on samples sorted with an FGFR3-IGH dual-color, dual-fusion
      translocation probe and an IGH dual-color break-apart rearrangement probe. The
      IGH deletions were found in 7 MM analyzed with the FGFR3-IGH probe and all
      confirmed by the IGH break-apart probe. The additional IGH signals were
      associated with different patterns using the IGH break-apart probe: a normal
      pattern in 9 cases, trisomy 14 in 3 cases, and splits of IGH in 7 cases. Fusion
      patterns with the FGFR3-IGH probe were observed in 13 cases. Atypical patterns
      were identified in 6 cases with multiple presentations of IGH: a deletion of the
      IGH variable segment in der(4) or in chromosome 14, loss of the IGH locus in
      chromosome 14, and additional copies of FGFR3-IGH fusion probes. We identified a
      majority of atypical IGH patterns with the t(4;14) probe, without false-negative
      results when FGFR3-IGH signal fusions were found. However, the extrapolation of
      FGFR3-IGH probe signals requires the IGH break-apart probe to obtain unequivocal
      interpretations.

PMID- 29040970
TI  - Use of Dipeptidyl-Peptidase IV Inhibitors and Bullous Pemphigoid.

PMID- 29040971
TI  - Characteristics and Outcomes of Vertebrobasilar Artery Dissection with
      Accompanied Atherosclerosis.
AB  - BACKGROUND: With the popularity of MRI use, vertebrobasilar artery dissection
      (VBD) has been found more frequently in patients with posterior circulation
      ischemic stroke (PCS). The relationship between VBD and atherosclerosis is
      unknown. The present study aimed to prove the hypothesis that PCS with pure VBD
      (p-VBD) and with VBD and accompanied cervical or cerebral artery atherosclerosis
      (a-VBD) have distinct manifestations. METHODS: Patients with VBD-related PCS who
      were prospectively enrolled in the Taipei Veterans General Hospital Stroke
      Registry between January 1, 2010 and August 31, 2014 were recruited for the
      present study. Patients who had (1) atherosclerotic plaques with or without
      stenotic flow in cervical arteries on Duplex ultrasonography or (2) focal >30%
      stenosis in cerebral arteries other than the dissecting region (usually in
      arterial bifurcations which are prone to atheroma formation) on brain MRA were
      defined as a-VBD. RESULTS: There were 91 patients (67 [73.6%] males, mean age
      65.5 years [SD = 15.2, range, 21-91]) with VBD-related PCS recruited for the
      present study; 31 were a-VBD and 60 were p-VBD. The results showed that there
      were significant differences in onset age, frequency of cigarette smoking,
      dissecting vascular involvement, and infarct locations between the 2 groups. In
      addition, compared with p-VBD, the a-VBD group had poorer functional recovery at
      3 months and 1 year, respectively, which was independent of age, sex, vascular
      risk factors, stroke severity at admission, and treatment options. CONCLUSION:
      VBD-related PCS with and without accompanied atherosclerosis had different
      manifestations and should be regarded as distinct arterial diseases.

PMID- 29040972
TI  - Regulation of Coronary Arterial Large Conductance Ca2+-Activated K+ Channel
      Protein Expression and Function by n-3 Polyunsaturated Fatty Acids in Diabetic
      Rats.
AB  - AIM: The objective of this study was to examine the effects of n-3
      polyunsaturated fatty acids (n-3 PUFAs) on coronary arterial large conductance
      Ca2+-activated K+ (BK) channel function in coronary smooth muscle cells (SMCs) of
      streptozotocin-induced diabetic rats. METHODS: The effects of docosahexaenoic
      acid (DHA) and eicosapentaenoic acid (EPA) on coronary BK channel open
      probabilities were determined using the patch clamp technique. The mRNA and
      protein expressions of BK channel subunits were measured using qRT-PCR and
      Western blots. The coronary artery tension and coronary SMC Ca2+ concentrations
      were measured using a myograph system and fluorescence Ca2+ indicator. RESULTS:
      Compared to nondiabetic control rats, the BK channel function was impaired with a
      reduced response to EPA and DHA in freshly isolated SMCs of diabetic rats. Oral
      administration of n-3 PUFAs had no effects on protein expressions of BK channel
      subunits in nondiabetic rats, but significantly enhanced those of BK-beta1 in
      diabetic rats without altering BK-alpha protein levels. Moreover, coronary ring
      tension induced by iberiotoxin (a specific BK channel blocker) was increased and
      cytosolic Ca2+ concentrations in coronary SMCs were decreased in diabetic rats,
      but no changes were found in nondiabetic rats. CONCLUSIONS: n-3 PUFAs protect the
      coronary BK channel function and coronary vasoreactivity in diabetic rats as a
      result of not only increasing BK-beta1 protein expressions, but also decreasing
      coronary artery tension and coronary smooth muscle cytosolic Ca2+ concentrations.

PMID- 29040973
TI  - Sulforaphane and Epigallocatechin Gallate Restore Estrogen Receptor Expression by
      Modulating Epigenetic Events in the Breast Cancer Cell Line MDA-MB-231: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND/AIMS: Epigenetics refers to modifications in gene activity and
      expression without alteration at the DNA sequence. Environment and diet could
      influence gene expression. Diet modifications may be meaningful in preventing and
      treating chronic diseases, cancer included. Dietary bioactive compounds, such as
      polyphenols (e.g., curcumin, resveratrol, or epigallocatechin gallate [EGCG]) or
      isothiocyanate (e.g., sulforaphane [SFN]), can regulate histone acetylation. The
      aim of this systematic review and meta-analysis was to evaluate the effect of SFN
      and EGCG on breast cancer (BC) cells cultured in vitro. METHODS: Due to the
      enormous variability observed in study protocols and the innumerable genes
      involved, only studies analyzing the number of apoptotic cells in the MDA-MB-231
      cell line were evaluated. The effect size (ES) was computed as the ratio of
      means. RESULTS: We identified 7 studies, 4 regarding the effect of 10 uM SFN on
      MDA-MB-231 cells (ES = 4.59, 95% confidence interval 4.05-5.20) and 3 focusing on
      the impact of 20 uM EGCG (ES = 2.84, 95% confidence interval 2.60-3.10).
      CONCLUSION: The findings suggest beneficial effects of dietary bioactive
      compounds such as SFN and EGCG and their effect on BC cells by restoring estrogen
      receptor gene expression, modulating epigenetic changes and events, and
      interfering with tumor growth rate. Publication bias limits the generalizability
      of the conclusions. High-quality studies are needed.

PMID- 29040975
TI  - Consensus Statements.

PMID- 29040974
TI  - An Intergroup Randomized Phase II Study of Bevacizumab or Cetuximab in
      Combination with Gemcitabine and in Combination with Chemoradiation in Patients
      with Resected Pancreatic Carcinoma: A Trial of the ECOG-ACRIN Cancer Research
      Group (E2204).
AB  - OBJECTIVES: Evaluate toxicity of two treatment arms, A (cetuximab) and B
      (bevacizumab), when combined with gemcitabine, and chemoradiation in patients
      with completely resected pancreatic carcinoma. Secondary objectives included
      overall survival (OS) and disease-free survival (DFS). METHODS: Patients with
      R0/R1 resection were randomized 1:1 to cetuximab or bevacizumab administered in
      combination with gemcitabine for two treatment cycles. Next three cycles included
      concurrent cetuximab/bevacizumab plus chemoradiation, followed by one cycle of
      cetuximab/bevacizumab. Cycles 7-12 included cetuximab/bevacizumab with
      gemcitabine. Cycles were 2 weeks. Frequency of specific toxicities was summarized
      for each treatment arm at two times during the study, after chemotherapy but
      prior to chemoradiation and after all therapy. RESULTS: A total of 127 patients
      were randomized (A, n = 65; B, n = 62). Prior to chemoradiation, the overall rate
      for toxicities of interest was 10% for arm A and 2% for arm B. After all therapy,
      the overall rates for toxicities of interest were 30 and 25% for arms A and B,
      respectively. Overall median OS and DFS were 17 and 11 months, respectively,
      which is not a significant improvement over expected survival rates for
      historical controls. CONCLUSIONS: Both treatments were tolerable with manageable
      toxicities, and were safe enough for a phase III trial had this been indicated.

PMID- 29040976
TI  - Diagnosing Psychopathy through Emotional Regulation Tasks: Heart Rate Variability
      versus Implicit Association Test.
AB  - BACKGROUND: Nowadays, the assessment of psychopathy relies on semistructured
      interviews plus file reviews. In order to improve the predictive validity of
      psychopathy at the individual level, tools that are not based on the rating of
      signs and symptoms are in great need. SAMPLING AND METHODS: The present study was
      conducted in a representative sample of 204 Spanish sentenced inmates. These
      inmates have served at least 6 months of their sentence at the Pereiro de Aguiar
      (Ourense, Spain) penitentiary. Psychopathy signs and symptoms were scored through
      interview and file review. The Implicit Association Test (IAT) and heart rate
      variability (HRV) experiments were also conducted. The Iowa Gambling Task (IGT)
      was performed as a control measure. RESULTS: Spectral HRV indices were able to
      detect psychopathic inmates at a significant level, while IAT experiments and the
      IGT could not discriminate them. HRV indices showed a more significant difference
      when assessing the affective-interpersonal dimensions of psychopathy.
      CONCLUSIONS: An HRV experiment is better than IAT in order to detect psychopathy
      in a representative sample of Spanish inmates.

PMID- 29040977
TI  - Gene Microarray Integrated with High-Throughput Proteomics for the Discovery of
      Transthyretin in Rhabdomyolysis-Induced Acute Kidney Injury.
AB  - BACKGROUND/AIMS: Rhabdomyolysis, one of the leading causes of acute kidney injury
      (AKI), develops after trauma, drug toxicity, infections, burns, and physical
      exertion. The aim of this study was to investigate differences in gene and
      protein expression to elucidate the pathogenesis of rhabdomyolysis (RM)-induced
      AKI. METHODS: In this study, we used glycerol induced renal injury as a model of
      RM-induced AKI. Affymetrix U133 plus 2.0 microarrays were used to perform gene
      microarray analysis. Isobaric tagging with related and absolute quantitation
      (iTRAQ) labeling mass spectrometry (MS) was applied to screen and identify
      differentially expressed proteins between RM-induced AKI and normal murine renal
      tissue. Verification experiments included immunohistochemistry (IHC), real-time
      PCR, Western blotting, and the measurement of ATP and ROS production. HK-2 cells
      were incubated in vitro with ferrous myoglobin and pcDNA-TTR, followed by assays
      to detect cell proliferation, ROS and apoptosis. RESULTS: According to gene
      microarray and iTRAQ-MS analysis, we screened 17 common elements. After multiple
      analyses, we selected transthyretin (TTR) as our focus and investigated TTR in
      the kidney. Verification experiments with IHC confirmed differential expression
      levels of TTR proteins. Furthermore, Western blotting showed a stepwise decrease
      in TTR in AKI renal tissues. Cell-based experiments showed that overexpression of
      TTR could improve HK-2 cell viability and inhibit apoptosis. TTR reduced
      apoptosis by decreasing the accumulation of reactive oxygen species (ROS).
      CONCLUSION: This study reports a possible mechanism for RM-induced AKI and
      suggests that reductions in TTR could increase the generation of ROS and induce
      apoptosis. TTR may be a potentially valuable target for RM-induced AKI.

PMID- 29040980
TI  - New Era of the Management of Liver Diseases and Liver Cancer: State-of-the-Art
      Progress in 2017.

PMID- 29040978
TI  - Hydrogen-Rich Saline Attenuates Brain Injury Induced by Cardiopulmonary Bypass
      and Inhibits Microvascular Endothelial Cell Apoptosis Via the PI3K/Akt/GSK3beta
      Signaling Pathway in Rats.
AB  - BACKGROUND/AIMS: Cardiopulmonary bypass (CPB) is prone to inducing brain injury
      during open heart surgery. A hydrogen-rich solution (HRS) can prevent oxidation
      and apoptosis, and inhibit inflammation. This study investigated effects of HRS
      on brain injury induced by CPB and regulatory mechanisms of the PI3K/Akt/GSK3beta
      signaling pathway. METHODS: A rat CPB model and an in vitro cell hypoxia model
      were established. After HRS treatment, Rat behavior was measured using
      neurological deficit score; Evans blue (EB) was used to assess permeability of
      the blood-brain barrier (BBB); HE staining was used to observe pathological
      changes; Inflammatory factors and brain injury markers were detected by ELISA;
      the PI3K/Akt/GSK3beta pathway-related proteins and apoptosis were assessed by
      western blot, immunohistochemistry and qRT -PCR analyses of brain tissue and
      neurons. RESULTS: After CPB, brain tissue anatomy was disordered, and cell
      structure was abnormal. Brain tissue EB content increased. There was an increase
      in the number of apoptotic cells, an increase in expression of Bax and caspase-3,
      a decrease in expression of Bcl2, and increases in levels of Akt, GSK3beta, P
      Akt, and P-GSK3beta in brain tissue. HRS treatment attenuated the inflammatory
      reaction ,brain tissue EB content was significantly reduced and significantly
      decreased expression levels of Bax, caspase-3, Akt, GSK3beta, P-Akt, and P
      GSK3beta in the brain. After adding the PI3K signaling pathway inhibitor,
      LY294002, to rat cerebral microvascular endothelial cells (CMECs), HRS could
      reduce activated Akt expression and downstream regulatory gene phosphorylation of
      GSK3beta expression, and inhibit CMEC apoptosis. CONCLUSION: The
      PI3K/Akt/GSK3beta signaling pathway plays an important role in the mechanism of
      CPB-induced brain injury. HRS can reduce CPB-induced brain injury and inhibit
      CMEC apoptosis through the PI3K/Akt/GSK3beta signaling pathway.

PMID- 29040981
TI  - Abdominal Ultrasound Findings of Tumor-Forming Hepatic Malignant Lymphoma.
AB  - AIM/BACKGROUND: Evaluations of abdominal ultrasonography (US) findings of primary
      and secondary tumor-forming hepatic malignant lymphoma (HML) have not been
      adequately reported. In this study, we elucidated US and contrast-enhanced US
      (CEUS) findings in patients with HML. MATERIALS/METHODS: From January 2006 to
      March 2017, 25 patients with HML were enrolled (primary 7, secondary 18), each of
      whom was diagnosed pathologically. They were divided into 2 groups based on tumor
      diameter (cutoff, 30 mm). US imaging findings were retrospectively analyzed.
      RESULTS: All tumors in patients with a small HML (<30 mm in diameter, small
      group, n = 14) were revealed as homogeneous hypo-echoic type (100%), with
      penetrating sign observed in only 1 patient. Tumors in 11 patients in the small
      group, examined with CEUS, showed homogeneous enhancement in the early vascular
      phase (91%) and a washout pattern in the portal phase (100%), and they were
      revealed as defective in the post-vascular phase (100%). In the large group (>=30
      mm; n = 11), tumors were revealed as a heterogeneous hypo-echoic lesion in 10
      (91%) and penetrating sign was observed in 8 (73%). Dilatation of the distal
      intrahepatic bile duct by the tumor was observed in 4 patients in the large
      group. In 7 large group patients examined with CEUS, imaging findings in the
      early vascular phase varied, with 5 (71%) showing a washout pattern in the portal
      phase and 5 (71%) revealed as defective in the post-vascular phase. CONCLUSION:
      We found that US imaging features of HML differ depending on the tumor diameter.

PMID- 29040982
TI  - Clinicopathological Study of Autoimmune Hepatitis Cases That Were Difficult to
      Differentiate from Drug-Induced Liver Injury.
AB  - AIM: Acute-onset autoimmune hepatitis (AIH) histopathologically presents with
      features of acute hepatitis and lacks a specific diagnostic method. Also, AIH is
      often difficult to differentiate from drug-induced liver injury (DILI). We aimed
      to investigate the final clinical diagnosis of these cases, and compare the
      clinical, biochemical, and histological characteristics of AIH vs. DILI. METHODS:
      We examined the Digestive Disease Week Japan 2004 (DDW-J) scale scores, AIH
      scores, clinical data, and pathological findings in 20 patients in whom it was
      difficult to differentiate autoimmune liver disease from DILI. RESULTS: In cases
      with a DDW-J scale score of >=5, there was a good correlation between the final
      diagnosis and DDW-J scale assessments, but in cases with a DDW-J scale score of
      ?4 they did not correlate well. The scores for pathological findings, such as
      cobblestone hepatocellular change (p = 0.015), interface hepatitis (p = 0.012),
      and prominent plasma cells in portal areas (p = 0.011), were higher in the AIH
      group than in the DILI group. CONCLUSION: This study showed that DDW-J scale was
      useful for differentiating AIH from DILI in cases with a DDW-J scale score of ?5.
      The histologic features of AIH were characterized by cobblestone hepatocellular
      change, interface hepatitis, and plasma cell infiltration of the portal region.

PMID- 29040983
TI  - Diagnosis of Fibrosis and Activity by a Combined Use of Strain and Shear Wave
      Imaging in Patients with Liver Disease.
AB  - OBJECTIVE: Performing shear wave imaging is simple, but can be difficult when
      inflammation, jaundice, and congestion are present. Therefore, the correct
      diagnosis of liver fibrosis using shear wave imaging alone might be difficult in
      mild-to-moderate fibrosis cases. Strain imaging can diagnose liver fibrosis
      without the influence of inflammation. Therefore, the combined use of strain and
      shear wave imaging (combinational elastography) for cases without jaundice and
      congestion might be useful for evaluating fibrosis and inflammation. METHODS: We
      enrolled consecutive patients with liver disease, without jaundice or liver
      congestion. Strain and shear wave imaging, blood tests, and liver biopsy were
      performed on the same day. The liver fibrosis index (LF index) was calculated by
      strain imaging; real-time tissue elastography, and the shear wave velocity (Vs)
      was calculated by shear wave imaging. Fibrosis index (F index) and activity index
      (A index) were calculated as a multiple regression equation for determining
      hepatic fibrosis and inflammation using histopathological diagnosis as the gold
      standard. The diagnostic ability of F index for fibrosis and A index for
      inflammation were compared using LF index and Vs. RESULTS: The total number of
      enrolled cases was 388. The area under the receiver operating characteristic
      (AUROC) was 0.87, 0.80, 0.83, and 0.80, at diagnosis of fibrosis stage with an F
      index of F1 or higher, F2 or higher, F3 or higher, and F4, respectively. The
      AUROC was 0.94, 0.74, and 0.76 at diagnosis of activity grade with an A index of
      A1 or higher, A2 or higher, and A3, respectively. The diagnostic ability of F
      index for liver fibrosis and A index for inflammation was higher than for other
      conventional diagnostic values. CONCLUSIONS: The combined use of strain and shear
      wave imaging (combinational elastography) might increase the positive diagnosis
      of liver fibrosis and inflammation.

PMID- 29040984
TI  - Ability of Cytokeratin-18 Fragments and FIB-4 Index to Diagnose Overall and Mild
      Fibrosis Nonalcoholic Steatohepatitis in Japanese Nonalcoholic Fatty Liver
      Disease Patients.
AB  - BACKGROUND: Several laboratory markers used in lieu of liver biopsy are
      reportedly useful in the diagnosis of nonalcoholic steatohepatitis (NASH). In the
      present study, we investigated the diagnostic impact of various non-invasive
      markers for predicting NASH. METHODS: A total of 229 nonalcoholic fatty liver
      disease (NAFLD) patients who underwent liver biopsy were enrolled for the study.
      The diagnostic ability of various markers to diagnose NASH from NAFLD was
      investigated. RESULTS: A total of 140 patients were histologically diagnosed with
      NASH. Of these, 104 had degree 0-2 fibrosis (F0-2), and 36 had degree 3-4
      fibrosis (F3-4). Multiple logistic regression analysis identified hyaluronic acid
      (HA) (OR 1.014; 95% CI 1.002-1.026; p = 0.024), FIB-4 index (OR 2.097; 95% CI
      1.177-3.735; p = 0.012), and cytokeratin-18 fragments (CK-18F) (OR 1.002; 95% CI
      1.001-1.002; p < 0.001) as factors independently associated with the diagnosis of
      NASH. The areas under the receiver operating characteristic curves (AUROCs) of
      HA, FIB-4 index, and CK-18F for the diagnosis of NASH were 0.77, 0.76, and 0.72,
      respectively. In addition, FIB-4 index (OR 1.907; 95% CI 1.063-3.419; p = 0.03)
      and CK-18F (OR 1.002; 95% CI 1.001-1.002; p < 0.001) could differentiate between
      NASH and NAFL, even when NASH patients with advanced fibrosis (F3-4) were
      excluded. AUROCs of FIB-4 index and CK-18F for the diagnosis of NASH with mild
      fibrosis (F0-2) from NAFLD were 0.70 and 0.70, respectively. CONCLUSIONS: FIB-4
      index and CK-18F have good diagnostic abilities not only for NASH overall, but
      also for NASH with mild fibrosis.

PMID- 29040985
TI  - Serum IFN-lambda3 Levels Correlate with Serum Hepatitis C Virus RNA Levels in
      Symptomatic Patients with Acute Hepatitis C.
AB  - BACKGROUND: Recent genome-wide association studies demonstrated that 2 single
      nucleotide polymorphisms (SNPs), upstream of the interferon-lambda (IFNL) 3 gene,
      are associated with the spontaneous clearance of hepatitis C virus (HCV) in
      symptomatic patients with acute hepatitis C (AHC). Although these 2 SNPs,
      rs8099917 and rs12979860, have established their significant roles in the innate
      immunity response to spontaneously clear HCV in patients with AHC, the detailed
      mechanisms of their roles remain largely unknown. AIM: This study is aimed at
      clarifying the factors affecting IFNL3 production and assessing the roles of
      IFNL3 in AHC. MATERIALS AND METHODS: A total of 21 AHC patients who visited the
      hospital within 10 days after symptom onset were assessed. As controls, 23
      healthy volunteers (HVs) were examined. Serum IFNL3 levels were quantified using
      an in-house, IFNL3-specific chemiluminescence enzyme immunoassay (CLEIA) kit.
      Serum IFNL1, IFN-alpha, IFN-beta, and IFN-gamma induced protein-10 (IP-10) levels
      were assayed using commercial enzyme-linked immunosorbent assay (ELISA) kits.
      RESULTS: At baseline, serum IFNL3 levels were higher in AHC patients than in HVs
      (p < 0.0001). The higher levels in AHC patients did not differ between patients
      with the rs8099917 TT genotype and those with the non-TT (TG/GG) genotype (p =
      0.546). Serial measurement of serum IFNL3 levels did not predict the outcome of
      conventional AHC. However, serum IFNL3 levels at baseline correlated positively
      with the HCV RNA levels (p = 0.005). Following HCV eradication, serum IFNL3
      levels reduced to within the range obtained for HVs. Baseline serum IFNL1 levels
      did not differ significantly between AHC patients and HVs (p = 0.284). Serum
      levels of IFNL1 and IFNL3 at baseline also showed no correlative power (p =
      0.288). Serum IFN-alpha and IFN-beta were detected together with remarkably high
      serum IFNL3 levels in only one patient who progressed to acute liver failure
      (ALF). CONCLUSION: These findings indicate that serum IFNL3 levels at baseline
      are higher in AHC patients regardless of the rs8099917 polymorphism, and primary
      HCV infection triggers the production of IFNL3. As a first line of defense in the
      innate immune system against invading HCV, increased IFNL3 levels play an
      important role, but serum IFNL3 levels are not the principal determinant of the
      clinical course of conventional AHC.

PMID- 29040987
TI  - Hepatocarcinogenesis Is Associated with Serum Albumin Levels after Sustained
      Virological Responses with Interferon-Based Therapy in Patients with Hepatitis C.
AB  - OBJECTIVE: It is a generally accepted fact that eradication of hepatitis virus C
      inhibits the subsequent development of hepatocellular carcinoma (HCC). On the
      contrary, a significant population of patients developed HCC despite sustained
      virological responses (SVRs) to interferon (IFN) therapy. METHODS: A total of 415
      patients with chronic hepatitis C, who were treated at our hospital between 2004
      and 2014, were enrolled for this study. We examined the risk factors for HCC
      development after IFN therapy. RESULTS: After analyzing various clinical
      parameters, it was concluded that a serum albumin (ALB) level <4.0 g/dL and the
      presence or absence of SVR achievement were risk factors for the development of
      HCC. When analyzing pre- and posttreatment factors, only a serum ALB level <4.0
      g/dL was considered a significant risk factor. The presence or absence of liver
      fibrosis progression was not identified as a risk factor. CONCLUSIONS: In
      patients with a serum ALB level <4.0 g/dL before IFN therapy, hepatic
      carcinogenesis after SVR achievement need to be considered. Furthermore, the
      serum ALB level may be more useful than the degree of fibrosis for the prediction
      of HCC after SVR in chronic hepatitis C.

PMID- 29040986
TI  - Comparison of Sofosbuvir Plus Ribavirin Treatment with Pegylated Interferon Plus
      Ribavirin Treatment for Chronic Hepatitis C Genotype 2.
AB  - BACKGROUND: Sofosbuvir plus ribavirin (RBV) therapy showed higher sustained
      virological response at 12 weeks after treatment (SVR12) than pegylated
      interferon (peg-IFN) plus RBV; however, liver function, fibrosis, and
      hepatocellular carcinoma markers have not been assessed so far. SUMMARY: Patients
      (n = 21) receiving Sofosbuvir plus RBV and those (n = 24) receiving peg-IFN plus
      RBV were enrolled in this study. Changes in alanine aminotransferase (ALT) and
      alpha-fetoprotein (AFP) levels, platelet (PLT) counts, FIB-4, and aspartate
      aminotransferase-to-platelet ratio index (APRI) in both groups were assessed in
      patients achieving SVR12. Also, fibrosis regression was assessed using
      pathophysiological biomarkers, such as hyaluronic acid, bone morphogenetic
      protein 7 (BMP-7), and connective tissue growth factor (CTGF) in the Sofosbuvir
      plus RBV group. In both groups, while the reduction in ALT levels was significant
      that of AFP was not. Compared with the baseline, although serum PLT count at the
      end of treatment (EOT) was significantly higher in the Sofosbuvir plus RBV group,
      it was significantly lower in the peg-IFN plus RBV group. Although a significant
      decline in fibrosis markers such as FIB-4 and APRI was observed between the
      baseline and at EOT in the Sofosbuvir plus RBV group, no significant change of
      these markers was observed in the peg-IFN plus RBV group. Moreover, BMP-7 and
      CTGF were significantly lower at EOT than the baseline in the Sofosbuvir plus RBV
      group. Key Message: The treatment with Sofosbuvir plus RBV results in not only a
      higher SVR, but also improves the liver function and the degree of fibrosis.

PMID- 29040989
TI  - Hepatocellular Carcinoma after Achievement of Sustained Viral Response with
      Daclatasvir and Asunaprevir in Patients with Chronic Hepatitis C Virus Infection.
AB  - BACKGROUND: Interferon-based antiviral therapies against hepatitis C virus (HCV)
      infection have been shown to reduce the incidence of hepatocellular carcinoma
      (HCC) in patients with sustained viral response (SVR). Recently, direct-acting
      antivirals (DAAs) have been proven to be much more effective in achieving SVR
      than interferon-based therapies. However, whether DAAs can efficiently prevent
      the occurrence of HCC after SVR remains controversial. To clarify this issue, we
      analyzed the clinical features of patients in whom HCC developed after
      achievement of SVR with DAAs for chronic HCV infection. SUMMARY: Among patients
      who achieved SVR with daclatasvir and asunaprevir (n = 100), HCC developed in 17
      patients (HCC group; n = 17) and did not develop in 83 patients (non-HCC group; n
      = 83) during a mean observation period of 15 months. A multivariate Cox
      proportional hazards analysis identified past history of HCC and male sex as
      significant risk factors for the emergence of HCC after DAAs. Sixteen cases with
      HCC after DAAs were in the very early or early stage (16/17, 94.1%), and one case
      was in the advanced stage (1/17, 5.9%) with portal venous tumor thrombus.
      Radiofrequency ablation and/or transarterial chemoembolization were performed in
      most cases as curative therapy (16/17, 94.1%). Key Messages: SVR by DAAs did not
      completely prevent the occurrence of HCC. However, even if HCC did develop after
      SVR, curative anticancer therapy was applicable in most cases.

PMID- 29040988
TI  - Unique Characteristics Associated with Sustained Liver Damage in Chronic
      Hepatitis C Patients Treated with Direct Acting Antivirals.
AB  - BACKGROUND AND AIMS: Direct-acting antivirals (DAAs) dramatically improve the
      sustained virological response (SVR) of chronic hepatitis C (CHC) patients.
      However, continuous liver damage after SVR may be a risk of hepatocellular
      carcinoma (HCC). We clarified pretreatment characteristics related to sustained
      liver damage after SVR. METHODS: A total of 286 CHC patients were treated with an
      interferon-free DAA regimen. Among them, 250 patients achieved SVR for 12 weeks
      after the end of treatment (SVR12); these individuals were classified based on
      alpha-fetoprotein (AFP) and alanine transaminase (ALT) levels posttreatment.
      Baseline characteristics significantly associated with AFP >5 ng/mL and ALT level
      >=20 IU/L after SVR were clarified using multivariate analyses. RESULTS: Among
      the pretreatment factors examined, serum AFP values and the presence of fatty
      liver (FL) were significantly associated with abnormal AFP (p < 0.0001) and ALT
      levels 12 weeks after SVR12 (SVR24; p = 0.0109). For 126 patients who showed an
      increase in baseline AFP level, FL, fibrosis-4 (FIB-4) index, and albumin levels
      before treatment were related to abnormal AFP at SVR24 (p = 0.0005, 0.0232, and
      0.0400 for FL, FIB-4 index, and albumin, respectively). Similarly, for 150
      patients with abnormal baseline ALT levels, FL was associated with an ALT level
      >= 30 IU/L after SVR (p = 0.0430). CONCLUSIONS: High FIB-4 index, low albumin
      level, and FL before DAA treatment were associated with a risk of sustained liver
      damage with AFP and ALT elevation after SVR; patients with these factors should
      be carefully monitored for emergence of HCC.

PMID- 29040990
TI  - Non-Hypervascular Hypointense Hepatic Nodules during the Hepatobiliary Phase of
      Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid-Enhanced MRI as a
      Risk Factor of Intrahepatic Distant Recurrence after Radiofrequency Ablation of
      Hepatocellular Carcinoma.
AB  - BACKGROUND: Non-hypervascular hypointense hepatic nodules during the
      hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic
      acid (Gd-EOB-DTPA)-enhanced MRI have been reported to be associated with
      intrahepatic distant recurrence (IDR) after hepatectomy or radiofrequency
      ablation (RFA) for hepatocellular carcinoma (HCC). IDR is categorized into
      hypervascular transformation of non-hypervascular hypointense hepatic nodules and
      new intrahepatic recurrence. The aim of this study was to evaluate the
      relationship between non-hypervascular hypointense hepatic nodules on Gd-EOB-DTPA
      enhanced MRI and IDR after RFA, focusing on new intrahepatic recurrence. METHODS:
      Ninety-one consecutive patients with 115 HCCs undergoing pretreatment Gd-EOB-DTPA
      enhanced MRI and RFA for treatment of HCC were enrolled. RESULTS: Of the 91
      patients who underwent RFA for HCC, 24 had non-hypervascular hypointense hepatic
      nodules on pretreatment Gd-EOB-DTPA-enhanced MRI. Recurrences were observed in 15
      and 19 patients with and without non-hypervascular hypointense hepatic nodules,
      respectively. Of the 15 recurrences in patients with non-hypervascular
      hypointense hepatic nodules, 10 patients had new intrahepatic recurrences. The
      cumulative incidence of new intrahepatic recurrence was significantly higher in
      patients with non-hypervascular hypointense hepatic nodules than in those without
      non-hypervascular hypointense hepatic nodules (p < 0.0001). Multivariate analysis
      revealed that the presence of non-hypervascular hypointense hepatic nodules and
      Child-Pugh score were independent risk factors for new intrahepatic recurrence.
      CONCLUSIONS: Non-hypervascular hypointense hepatic nodules during the
      hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were a useful predictive factor
      for IDR, particularly for new intrahepatic recurrence, after RFA.

PMID- 29040991
TI  - Impact of Tumor Factors on Survival in Patients with Hepatocellular Carcinoma
      Classified Based on Kinki Criteria Stage B2.
AB  - BACKGROUND: Tumors classified based on the Barcelona Clinic Liver Cancer (BCLC)
      stage B hepatocellular carcinoma (HCC) are heterogeneous in nature. Previously,
      the Kinki criterion was proposed for a more precise subclassification of tumors
      in BCLC-stage B. However, tumors in sub-stage B2 include various size and number
      of HCCs even with the Kinki criteria, which could lead to heterogeneity for
      overall survival (OS). In this study, we assessed how the size and number of
      tumors affect the OS and time to progression (TTP) in patients with Kinki
      criteria stage B2 tumors and treated with transarterial chemoembolization (TACE).
      METHODS: Of 906 HCC patients treated with TACE at Kindai University Hospital, 236
      patients with HCC considered as Kinki criteria stage B2 were examined. They were
      classified into the following 4 groups according to the maximum tumor diameter
      and number of tumors: B2a group, tumor size <=6 cm and total number of tumors
      <=6; B2b group, size <=6 cm and number >6; B2c group, size >6 cm and number <=6;
      and B2d group, size >6 cm and number >6. The OS and TTP of patients in each group
      were compared. RESULTS: There were 131 patients (55.5%) in the B2a group, 58
      (24.6%) in the B2b group, 41 (17.4%) in the B2c group, and 6 (0.03%) in the B2d
      group. Comparison of the survivals revealed that the median OS was 2.8 years (95%
      CI 2.0-3.5) in the B2a group, 2.8 years (95% CI 2.0-3.3) in the B2b group, 1.9
      years (95% CI 0.8-4.0) in the B2c group, and 2.3 years (95% CI 1.2-ND [no data])
      in the B2d group, respectively (p = 0.896). The median TTP in B2a, B2b, B2c, and
      B2d sub-substage HCC were13.2, 12.1, 13.8, and 11.5 months, respectively (p =
      0.047). The median TTP in B2a + B2c sub-substage patients was longer than that in
      B2b + B2d sub-substage HCC patients (14.0 months and 10.4 months; p = 0.002).
      CONCLUSION: No significant differences were observed in the OS among HCC patients
      subclassified based on the maximum tumor diameter and tumor number in Kinki
      criteria stage B2. Consequently, Kinki criteria stage B2 HCC is a homogeneous
      subgroup in terms of OS prediction. However, shorter TTP in B2b+B2c sub-substage
      HCC patients than that in B2a + B2c sub-substage HCC patients suggests that
      different treatment strategy, such as systemic therapy with targeted agents
      instead of TACE, may be suitable to preserve the liver function.

PMID- 29040992
TI  - Time to Transcatheter Arterial Chemoembolization Refractoriness in Patients with
      Hepatocellular Carcinoma in Kinki Criteria Stages B1 and B2.
AB  - BACKGROUND: Transarterial chemoembolization (TACE) is recommended for patients
      with hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) stage
      B. However, because of the heterogeneity of HCC in BCLC stage B; various
      subclassification systems have been proposed to predict the prognosis of
      patients. Previously, we proposed the Kinki criteria for precise classification
      of HCC cases in BCLC stage B. In this study, we compared the time to TACE
      refractoriness in HCC patients with Kinki criteria substages B1 and B2-HCC.
      SUMMARY: Between January 2006 and December 2013, 592 HCC patients (substage B1, n
      = 118; substage B2, n = 170) underwent TACE. Time to progression under TACE
      treatment was defined as the time to untreatable progression (TTUP). TTUP and
      changes in liver function were analyzed in patients with substages B1 and B2-HCC.
      The median TTUP was 25.7 months (95% CI 19.3-37.3) and 16.4 months (95% CI 13.1
      20.2) in patients with substage B1-HCC and substage B2-HCC, respectively (p =
      0.0050). In patients with substage B2-HCC, median Child-Pugh scores after the
      first TACE session was significantly different from those after third and fifth
      TACE sessions (first-third, p = 0.0020; first-fifth, p = 0.0008). Key Message:
      TACE refractoriness occurred earlier in patients with substage B2-HCC than those
      with substage B1-HCC; deterioration of liver function with repeated TACE was more
      obvious in HCC cases with stage-B1 tumor. Shorter TTUP and impaired liver
      function due to repeated TACE could be responsible for the shorter survival in
      patients with substage B2-HCC.

PMID- 29040993
TI  - Hemodynamic Changes on Cone-Beam Computed Tomography during Balloon-Occluded
      Transcatheter Arterial Chemoembolization Using Miriplatin for Hepatocellular
      Carcinoma: A Preliminary Study.
AB  - BACKGROUND/AIM: Balloon-occluded transcatheter arterial chemoembolization (B
      TACE) using miriplatin (MPT) is anticipated as a new strategy for hepatocellular
      carcinoma (HCC). This study was aimed at evaluating the hemodynamic changes
      with/without balloon occlusion of the hepatic artery, correlation of cone-beam CT
      (CBCT) pixels, and CT value after B-TACE for HCC. METHODS: A total of 52 patients
      with HCC, who underwent B-TACE using MPT in addition to the balloon-occluded CBCT
      hepatic arteriography, were studied. RESULTS: After balloon occlusion, CBCT pixel
      values increased in 37 lesions, whereas it decreased in 15 lesions. Intratumoral
      CT values after B-TACE were lower with decreased CBCT pixel values than with
      increased CBCT pixel values. CONCLUSION: Hemodynamic changes on CBCT during
      balloon occlusion can be used to predict the efficacy of B-TACE using MPT.

PMID- 29040994
TI  - Sorafenib-Regorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: A
      Single-Institute Experience.
AB  - OBJECTIVES: Previously, no therapeutic agent has been known to improve the
      overall survival compared with placebo in patients with hepatocellular carcinoma
      (HCC), who have progressed after sorafenib. In this patient population,
      regorafenib was first demonstrated to confer a survival benefit in the RESORCE
      trial, and subsequently it was approved as a second-line treatment for patients
      with advanced HCC. An open-label expanded access program (EAP) of regorafenib was
      implemented for compassionate use. We investigated the efficacy and safety of
      regorafenib based on our experience of the RESORCE trial and the EAP. METHODS:
      Data from 5 patients from the RESORCE trial and 6 from the EAP were analyzed
      retrospectively. All patients had tolerated prior sorafenib and were progressing
      during sorafenib treatment. RESULTS: The median progression-free survival was 9.2
      months (95% CI 2.3-16.1). One patient achieved a partial response and 7 achieved
      stable disease. The objective response rate was 9.1%, and the disease control
      rate was 72.7%. No treatment-associated mortalities were observed. Grade 3
      hypophosphatemia was observed in 2 patients, grade 2 anorexia was observed in 5
      patients, and grade 3 neutropenia was observed in 2 patients. Grade 2 and grade 3
      thrombocytopenia were observed in 2 and 3 patients, respectively. All treatment
      related adverse events were improved by reduction or interruption of regorafenib.
      Five patients showed decreased serum albumin levels. CONCLUSION: Sorafenib and
      regorafenib sequential therapy presents a safe and effective treatment option for
      patients with advanced HCC.

PMID- 29040995
TI  - Role of Immune Checkpoint Blockade in the Treatment for Human Hepatocellular
      Carcinoma.
AB  - With the development of molecular targeting therapy, several treatment options
      for advanced hepatocellular carcinoma (HCC) have become available in cases where
      curative and other palliative treatments, such as radiofrequency ablation,
      surgical resection, and transarterial chemoembolization, are not applicable.
      However, with the detection of a variety of mutations in cancer-related genes in
      a single tumor, molecular heterogeneity is commonly observed in HCC. Therefore,
      mutations in the major cellular signaling pathways underlie the development of
      resistance to molecular targeting agents. On the contrary, immune checkpoint
      inhibitors have proven effective in patients who are refractory to conventional
      treatments and molecular targeting therapy. Several clinical trials are currently
      investigating the efficacy of immune checkpoint inhibitors both individually and
      in combination with other types of anticancer agents. In this review, we focus on
      the potential of immune checkpoint blockade in the treatment of human HCC.

PMID- 29040998
TI  - Erratum.

PMID- 29040999
TI  - Hepatic Function during Repeated TACE Procedures and Prognosis after Introducing
      Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: Multicenter
      Analysis.
AB  - BACKGROUND/AIM: We evaluated the relationship of hepatic function with repeated
      transarterial catheter chemoembolization (TACE) and prognosis after sorafenib
      treatment in various patient cohorts. METHODS: Study 1 comprised of 212 Barcelona
      clinic liver cancer stage-B (BCLC-B) HCC patients classified as Child-Pugh A (CP
      A) and who had received repeated TACE treatments (r-TACE) (naive:recurrence =
      66:146). Study 2 comprised of 435 patients with unresectable HCC classified as CP
      A in who sorafenib was introduced (naive:recurrence = 37:398; CP score 5:6 =
      282:153; macro-vessel invasion [MVI]+: extrahepatic metastasis [EHM]+ both
      negative = 124:226:143). Changes in hepatic function along with CP and albumin
      bilirubin (ALBI) score/grade during r-TACE in Study 1, and prognosis after
      introducing sorafenib in Study 2 were evaluated. RESULTS: Hepatic function
      worsened to CP-B in 9-14% with each TACE procedure, while 18-21% had a change of
      classification from ALBI-1 to ALBI-2. When the prognosis of patients with the
      best CP score of 5 was analyzed, those with ALBI-1 (n = 154) had a better outcome
      than those with ALBI-2 (n = 128) (MST 17.5 vs. 9.9 months; p = 0.01), while ALBI
      1 (n = 43) patients also showed a better outcome than ALBI-2 (n = 34) patients
      with a CP score of 5 without MVI/EHM (MST: 17.5 vs. 10.0 months; p = 0.029). The
      Akaike's Information criterion for ALBI-grade (MST: grade 1 vs. 2 = 16.9 vs. 10.4
      months; p = 0.001) was also better than that for CP (MST: score 5 vs. 6 = 14.4
      vs. 10.5 months; p = 0.003) (3195.6 vs. 3197.5) in all 435 patients. CONCLUSION:
      The rate of patients with downgraded hepatic function during r-TACE, especially
      with regard to ALBI-grade, was not low. ALBI-grade was shown to be a better
      hepatic function assessment tool than CP in patients receiving sorafenib
      treatment. Strict judgment of TACE-refractory status in patients with
      unresectable HCC is needed to improve prognosis before downgrading the hepatic
      function.

PMID- 29041000
TI  - Genetic Variations of Oxidative Stress Related Genes ALOX5, ALOX5AP and MPO
      Modulate Ischemic Stroke Susceptibility Through Main Effects and Epistatic
      Interactions in a Chinese Population.
AB  - BACKGROUND/AIMS: To investigate the roles of the oxidative stress related-genes
      ALOX5, ALOX5AP and MPO in ischemic stroke susceptibility in the Han Chinese
      population. METHODS: A total of 351 ischemic stroke patients and 417 controls
      were recruited. The ALOX5 rs10900213, ALOX5AP rs4293222 and MPO rs2107545 gene
      polymorphisms were genotyped. RESULTS: We identified that rs2107545 of MPO gene
      was significantly associated with ischemic stroke susceptibility after adjusting
      for covariates. Furthermore, we also considered the likely complexity of
      oxidative stress and inflammatory process in stroke by assessing the combined
      effects of multiple genes. Generalized multifactor dimensionality reduction
      (GMDR) analysis revealed that the combination of ALOX5 rs10900213, ALOX5AP
      rs4293222 and MPO rs2107545 was significantly associated with increased risk of
      ischemic stroke (P=0.0040, OR (95% CI) =1.991 (1.241 to 3.195)). Additionally,
      the MPO rs2107545 genotype was significantly associated with clinical outcomes at
      6 months after discharge from the hospital. CONCLUSION: Our study revealed that
      epistatic interaction among the ALOX5, ALOX5AP and MPO genes played a significant
      role in vulnerability to ischemic stroke. Furthermore, these results also suggest
      that the rs2107545 of MPO gene can be used as a biomarker for the susceptibility
      and prognosis of ischemic stroke patients.

PMID- 29041001
TI  - HMGB1 Expression Level in Circulating Platelets is not Significantly Associated
      with Outcomes in Symptomatic Coronary Artery Disease.
AB  - BACKGROUND/AIMS: Platelets express high-mobility group box 1 (HMGB1), a damage
      associated molecular pattern molecule (DAMP) that triggers thrombosis and
      inflammation when present in extracellular space. The role of platelet-derived
      HMGB1 in coronary artery disease (CAD) remains unexplored. METHODS: In a cohort
      study, we measured the expression of HMGB1 on the surface of circulating
      platelets in 183 patients with symptomatic CAD (stable CAD: n=80, acute coronary
      syndrome, ACS: n=103) at the time of percutaneous coronary intervention. All
      patients were tracked for course of left ventricular ejection fraction (LVEF),
      all-cause death (ACD), and myocardial infarction (MI) for 360 days after study
      inclusion. RESULTS: Platelet HMGB1 expression did not significantly differ
      between stable CAD, unstable CAD, non-ST segment elevation myocardial infarction
      (NSTEMI), and ST segment elevation myocardial infarction (STEMI). Moreover,
      platelet HMGB1 did not significantly correlate with LVEF, neither at baseline nor
      at 6 months follow-up of the MI subgroup, and did not exert any significant
      effect on outcome (composite of ACD and/or MI as well as single events ACD and
      MI). Cumulative event-free survival of patients was not significantly different
      between HMGB1 levels above the median and HMGB1 levels below or equal to the
      median. CONCLUSION: These findings suggest that HMGB1 expressed on the surface of
      circulating platelets in patients with symptomatic CAD may not serve as a
      prognostic biomarker for this disease state.

PMID- 29041003
TI  - Depression in the Context of Medical Disorders: New Pharmacological Pathways
      Revisited.
AB  - The depressive state has been characterised as one of elevated inflammation,
      changed cardiovascular parameters and a deranged metabolic situation all of which
      holds promise for a better understanding and handling of treatment-resistance in
      affective disorders as well as for future developments in treatment algorithms.
      In this context several biomarkers are differentially regulated by antidepressant
      treatment and connected to metabolic, inflammatory, cardiovascular and apoptotic
      components of the pathophysiology, i.e. adiponectin, apolipoprotein-B, B-type
      natriuretic peptide, cortisol, CRP, cysteine, homocysteine, fibrinogen,
      adiponectin, BMI, glycated hemoglobin A1c, leptin, interferon-gamma, high-density
      lipoprotein, interleukin interleukin-1alpha, -1beta, -2, -4, -5, -6, -8, -10, 
      12, -13, -17, insulin-like growth factor-1, low-density lipoprotein,
      myeloperoxidase, osteoprotegerin, tumour necrosis factor alpha, troponins,
      triglycerides etc. In this context antidepressants exert different modulatory
      effects on the outcome, incidence and mortality concerning several severe
      disorders, i.e. cancer, diabetes, stroke, inflammation, stroke and cardiovascular
      risk. Vice versa different drugs used in the treatment of these disorders have a
      favourable effect in depressive states, e.g. statins, aspirine, NSAIDs,
      pioglitazone, celecoxib, peroxisome proliferator-activated receptor-gamma
      agonists and minocycline. In this review, actions of different antidepressant
      treatment strategies on cancer, stroke, diabetes and cardiovascular disorders are
      shown and the influence on the outcome of the disorders is differentially
      discussed. In conclusion a hypothetic model for the implication of actual
      findings in everyday clinical practice is proposed. In this context personalized
      treatment could be used to tailor treatment to specific individuals according to
      their clinical endophenotypes. Moreover a potential target for the development of
      novel intervention strategies might be used.

PMID- 29041002
TI  - Astragaloside IV Induced miR-134 Expression Reduces EMT and Increases
      Chemotherapeutic Sensitivity by Suppressing CREB1 Signaling in Colorectal Cancer
      Cell Line SW-480.
AB  - BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer
      related deaths worldwide. Although chemotherapy is the primary means in
      colorectal cancer treatment, it is burdenerd by adverse drug effects. Drug
      resistance is one of the most important challenges for chemotherapy and
      epithelial-mesenchymal transition (EMT) plays critical role in the development of
      drug resistance. AIMS: The aim of this study was to investigate the mechanisms
      underlying the effect of astragaloside IV (AS-IV) on miR-134 expression, EMT and
      chemotherapeutic sensitivity in CRC. METHODS: Cell proliferation, transfection
      assay, western blot, real-time PCR, cell migration and invasion assay and
      luciferase reporter assay were used to detect the effects of AS-IV on CRC.
      RESULTS: AS-IV significantly inhibited CRC cell migration and invasion by
      inducing miR-134 expression. Moreover, AS-IV and miR-134 increased the
      sensitivity of CRC tumors to oxaliplatin (OXA) chemotherapy. cAMP responsive
      element-binding protein 1 (CREB1), which was required for CRC cells migration,
      invasion and drug sensitivity, was significantly down-regulated by AS-IV.
      CONCLUSIONS: Our results indicated that AS-IV inhibited CRC EMT by inducing miR
      134 expression which significantly down-regulated the CREB1 signaling pathway,
      and therefore increased the sensitivity to chemotherapy. Our findings provided
      new insight into the mechanisms of chemotherapy-resistant CRC, and may open new
      therapeutic options in the treatment of this devastating disease.

PMID- 29041004
TI  - Impact of Beta-Blockade on Cardiac Events in Patients with Chronic Severe
      Nonischemic Mitral Regurgitation.
AB  - OBJECTIVES: The aim of this study was to examine the impact of beta-blockade on
      cardiac events among patients with initially asymptomatic chronic severe
      nonischemic mitral valve regurgitation (MR). METHODS: Data from 52 consecutive
      patients in our prospective natural history study of isolated chronic severe
      nonischemic MR were assessed post hoc over 19 years to examine the relation of
      chronic beta-blockade use to subsequent cardiac events (death or indications for
      mitral valve surgery, MVS). At entry, all patients were free of surgical
      indications; 9 received beta-blockers. Cardiac event rate differences were
      analyzed by Kaplan-Meier log rank comparison. RESULTS: During follow-up, cardiac
      events included sudden death (1), heart failure (8), atrial fibrillation (6),
      left ventricular dimensions at systole >=4.5 cm (11), left ventricular ejection
      fraction <60% (6), right ventricular ejection fraction <35% (2), and a
      combination of cardiac events (7). The cardiac event risk was 4-fold higher among
      patients receiving beta-blockers (average annual risk = 60.6%) versus those not
      receiving beta-blockers (average annual risk = 15.2%; p = 0.001). These effects
      remained statistically significant (p = 0.005) when analysis was adjusted for
      other baseline covariates. CONCLUSIONS: Beta-blockade appears to confer an
      increased risk of sudden cardiac death or indications for MVS among patients with
      chronic severe nonischemic MR. Randomized trials are needed to confirm these
      findings.

PMID- 29041006
TI  - Deciphering the Social Organization and Structure of Wild Yunnan Snub-Nosed
      Monkeys (Rhinopithecus bieti).
AB  - The social organization of natural groups of Rhinopithecus bieti (Yunnan snub
      nosed monkey) is virtually unknown. We studied the demography and social
      structure of a free-ranging group at Samage Forest, China, for nearly 2 years.
      This study confirmed that R. bieti exhibits a multilevel social organization of
      core 1-male units (OMUs) that congregate in a band of >400 members. Even though
      the band appeared to be unified for the most part, we also witnessed occasional
      fission-fusion. OMUs were cohesive entities, and their members were spatially and
      socially isolated from members of other OMUs. Large all-male units associated
      with the band, and when they closely followed OMUs there was a tendency for
      elevated male aggression. Within OMUs, females associated preferentially with
      males and vice versa, resulting in a bisexually bonded society. Contrary to other
      Asian colobines, R. bieti were comparatively social, with grooming occupying 7.3%
      of the time. Social grooming was primarily a female affair, but males also
      participated in grooming networks. The integration of males into the social
      network of the OMU is thought to help to maintain OMU integrity and cohesion with
      other social units being in close proximity.

PMID- 29041005
TI  - Cardiogenic Shock during First Infusion of Anthracycline Chemotherapy in a
      Patient with Hodgkin Lymphoma: An Unusual Event.
AB  - INTRODUCTION: Hodgkin lymphoma (HL) is one of the most common types of cancers of
      the lymphatic system. The currently available therapies enable a cure in
      approximately 80-85% of treated patients. However, the cardiotoxicity of HL
      treatment has become a major cause of morbidity and mortality in survivors mainly
      related to the use of anthracycline. CASE REPORT: An HL, staged IIIB, was
      diagnosed in a 60-year-old man with no cardiovascular disease. During the first
      cycle of ABVD chemotherapy (Adriamycin; bleomycin; vinblastine; dacarbazine),
      near the end of the dacarbazine infusion, the patient presented a sudden
      cardiogenic shock characterized by a severe left ventricular systolic
      dysfunction. Laboratory and instrumental examinations performed did not suggest
      any specific etiology. After 15 days of medical support, the patient presented a
      complete cardiac function and clinical recovery. Subsequently bendamustine
      chemotherapy was started because of its limited extrahematological toxicity, but
      after 4 cycles the patient had progressive disease and died of septic shock. We
      concluded that a very rare hyperacute anthracycline cardiotoxicity was the most
      likely reason for this critical scenario. CONCLUSIONS: This rare event stresses
      our inability to correctly predict the risk of a patient developing
      cardiotoxicity and also highlights the need to improve the knowledge of
      underlying pathophysiological mechanisms; in fact, it suggests a possible genetic
      predisposition to develop cardiotoxicity due to a relatively limited dosage.

PMID- 29041007
TI  - The Utilization Paradox.

PMID- 29041008
TI  - Increase of Substance P Concentration in Saliva after Pharyngeal Electrical
      Stimulation in Severely Dysphagic Stroke Patients - an Indicator of Decannulation
      Success?
AB  - BACKGROUND/AIMS: Substance P (SP) is a neuropeptide, likely acting as a
      neurotransmitter in the pharyngeal mucosa enhancing the swallow and cough reflex.
      Pharyngeal Electrical Stimulation (PES) induces a temporary increase of salivary
      SP levels in healthy adults. Previous evidence suggests that post-stroke
      dysphagia is related to reduced SP levels. Here, we investigated the effects of
      PES on SP levels in severely dysphagic stroke patients and a possible link
      between increase of SP and treatment success. METHODS: 23 tracheotomized stroke
      patients who could not be decannulated due to severe and persisting dysphagia
      according to endoscopic evaluation received PES for 10 minutes a day over three
      consecutive days in this prospective single-center study. If initial treatment
      failed, repetitive stimulation cycles were provided. Saliva samples were
      collected before and directly after each PES. RESULTS: 61% of participants were
      decannulated after the first treatment cycle. Increase of SP levels post
      stimulation was closely related to treatment success, i.e. decannulation with 79%
      of successfully treated patients showing increase of SP, whereas 89% of
      unsuccessfully treated patients had stable or decreased SP levels. Applying
      logistic regression analysis, increase of SP level remained the only independent
      predictor of decannulation after PES. All 3 repetitively treated patients showed
      increased SP levels when progressing from the 1st to the 2nd cycle, two of whom
      were decannulated hereafter. CONCLUSIONS: The physiological mechanism of PES may
      consist in restoration of sensory feedback, which is known to be crucial for the
      execution of a safe swallow. SP possibly acts as a biomarker for indicating
      response to PES.

PMID- 29041009
TI  - FCGR2A and FCGR3A Genotypes Correlate with Farletuzumab Response in Patients with
      First-Relapsed Ovarian Cancer Exhibiting Low CA125.
AB  - Farletuzumab is a humanized monoclonal antibody that binds to folate receptor
      alpha and elicits an anti-tumor response via immune effector activity. Recent
      studies from a global phase 3 trial in ovarian cancer patients treated with
      carboplatin/taxane plus farletuzumab found that the tumor-produced CA125 protein
      can suppress farletuzumab function via perturbing its engagement to the
      activating Fc-gamma receptors CD32a (FCGR2A) and CD16a (FCGR3A). Previous reports
      have indicated that naturally occurring polymorphisms in both of these receptors
      may play a role in their ability to engage therapeutic antibodies and elicit an
      optimal immune response via antibody-dependent cellular cytotoxicity (ADCC). In
      light of the importance of farletuzumab ADCC function for optimal tumor cell
      killing, we evaluated the frequency of FCGR2A-131H/R and FCGR3A-158V/F
      polymorphisms in 461 consenting patients from this global clinical study and
      their association with clinical outcome to placebo versus farletuzumab treatment.
      Here, we show that farletuzumab has enhanced binding to FCGR3A-158V high-affinity
      receptor and has an enhanced clinical outcome in patients with low baseline CA125
      levels and at least 1 high-affinity allele of FCGR2A or FCGR3A.

PMID- 29041010
TI  - A Comparative Study of Four Methods for the Detection of Nematode Eggs and Large
      Protozoan Cysts in Mandrill Faecal Material.
AB  - Coproscopical methods like sedimentation and flotation techniques are widely used
      in the field for studying simian gastrointestinal parasites. Four parasites of
      known zoonotic potential were studied in a free-ranging, non-provisioned
      population of mandrills (Mandrillus sphinx): 2 nematodes
      (Necatoramericanus/Oesophagostomum sp. complex and Strongyloides sp.) and 2
      protozoan species (Balantidium coli and Entamoeba coli). Different coproscopical
      techniques are available but they are rarely compared to evaluate their
      efficiency to retrieve parasites. In this study 4 different field-friendly
      methods were compared. A sedimentation method and 3 different McMaster methods
      (using sugar, salt, and zinc sulphate solutions) were performed on 47 faecal
      samples collected from different individuals of both sexes and all ages. First,
      we show that McMaster flotation methods are appropriate to detect and thus
      quantify large protozoan cysts. Second, zinc sulphate McMaster flotation allows
      the retrieval of a higher number of parasite taxa compared to the other 3
      methods. This method further shows the highest probability to detect each of the
      studied parasite taxa. Altogether our results show that zinc sulphate McMaster
      flotation appears to be the best technique to use when studying nematodes and
      large protozoa.

PMID- 29041011
TI  - Hemodiafiltration Reduces All-Cause and Cardiovascular Mortality in Incident
      Hemodialysis Patients: A Propensity-Matched Cohort Study.
AB  - BACKGROUND: The majority of studies suggesting that online hemodiafiltration
      reduces the risk of mortality compared to hemodialysis (HD) have been performed
      in dialysis-prevalent populations. In this report, we conducted an epidemiologic
      study of mortality in incident dialysis patients, comparing post-dilution online
      hemodiafiltration and high-flux HD, with propensity score matching (PSM) used to
      correct indication bias. METHODS: Our study cohort comprised 3,075 incident
      dialysis patients treated in 64 Spanish Fresenius Medical Care clinics between
      January 2009 and December 2012. The primary outcome of this study was to
      investigate the impact of the type of renal replacement on all-cause mortality.
      An analysis of cardiovascular mortality was defined as the secondary outcome. To
      achieve these objectives, patients were followed until December 2016. Patients
      were categorized as high-flux HD patients if they underwent this treatment
      exclusively. If >90% of their treatment was with online hemodiafiltration, then
      the patient was grouped to that modality. RESULTS: After PSM, a total of 1,012
      patients were matched. Compared with patients on high-flux HD, those on online
      hemodiafiltration received a median replacement volume of 23.45 (interquartile
      range 21.27-25.51) L/session and manifested 24 and 33% reductions in all-cause
      and cardiovascular mortality (all-cause mortality hazards ratio [HR] 0.76, 95% CI
      0.62-0.94 [p = 0.01]; and cardiovascular mortality HR 0.67, 95% CI 0.50-0.90 [p =
      0.008]). CONCLUSIONS: This study shows that post-dilution online
      hemodiafiltration reduces all-cause and cardiovascular mortality compared to high
      flux HD in an incident HD population.

PMID- 29041012
TI  - Wilms' Tumor Gene 1 (WT1) Peptide Vaccine Therapy for Hematological Malignancies:
      From CTL Epitope Identification to Recent Progress in Clinical Studies Including
      a Cure-Oriented Strategy.
AB  - The identification of human Wilms' tumor gene 1 (WT1) protein-derived cytotoxic T
      lymphocyte (CTL) epitopes and the in vivo efficacy of WT1 peptide-based
      immunotherapy in a mouse model were reported in 2000. This successful basic
      research led to clinical studies of a WT1 peptide vaccine, and a positive impact
      on clinical response was first demonstrated in 2003 in the form of a reduction in
      blast cells of vaccine-treated patients with myelodysplastic syndromes (MDS).
      Since then, data on WT1 peptide vaccine-treated patients with immunological
      and/or clinical response have been accumulated. MDS and acute myeloid leukemia
      were the major target diseases to provide proof of concept for the therapeutic
      potential of the WT1 peptide vaccine. WT1 vaccination-induced clinical responses
      or usefulness were also shown for chronic myeloid leukemia, multiple myeloma, and
      acute lymphoblastic leukemia, as well as various types of solid cancers. Non
      Hodgkin's lymphoma and myeloproliferative neoplasms may also be target diseases
      because of their WT1 expression. Of note, recent clinical studies have
      demonstrated that patients with hematological malignancies who have minimal
      residual disease after chemotherapy or allogeneic hematopoietic stem cell
      transplantation may be cured by WT1 peptide vaccination. Further enhancement of
      the efficacy and usefulness of the WT1 peptide vaccine is expected.

PMID- 29041013
TI  - Maternal Aneurysmal Subarachnoid Hemorrhage During Pregnancy as an
      Interdisciplinary Task.
AB  - Maternal aneurysmal subarachnoid hemorrhage (aSAH) during pregnancy presents a
      challenge regarding treatment and management. Due to the limited number of cases
      there are no treatment guidelines available. Thus, treatment is usually done on a
      case-by-case basis. Here we report on four cases of aSAH during pregnancy,
      describing the different management strategies and suggesting a possible
      treatment algorithm. Patients treated between 2003 and 2013 in our center were
      included in this retrospective study. Clinical data focused on time management
      concerning gestation week (GW), microsurgical or endovascular treatment, and
      outcome of the patients and the fetuses. Results were compared to the present
      literature on this issue. Mean age was 30.8 years, initial Hunt & Hess (H&H)
      grade ranged from III to V. All patients suffered from aSAH during the 3rd
      trimester of pregnancy. In the four cases, two emergency Caesarean sections (CS)
      were performed. Two aneurysms were occluded by microsurgical clipping and one was
      treated endovascularly. One patient died before definitive treatment of the
      aneurysm could be achieved, whereas fetal mortality was 0%. The mean follow-up
      was 83 months. aSAH during pregnancy needs individualized interdisciplinary
      management. Efforts must focus on the mother so that a delay in the best
      available treatment for the pregnant patient is avoided. Therefore treatment
      modality should be primarily determined by the aneurysm itself. However, timing
      in terms of delivery of the fetus and aneurysm treatment is a crucial point.

PMID- 29041014
TI  - Colon inflammatory fibroid polyp in a patient with von Recklinghausen's disease:
      endoscopic aspect with narrow-band imaging and magnification.

PMID- 29041015
TI  - Therapeutic application of linked color imaging for colorectal endoscopic mucosal
      resection.

PMID- 29041016
TI  - Removal of large colorectal lesions resected by endoscopic submucosal dissection
      using a laparoscopic bag.

PMID- 29041017
TI  - Single-session EUS-guided hepaticogastrostomy and dual-scope gastroenterostomy: a
      modified technique for palliative double endoscopic biliary and gastric bypass.

PMID- 29041018
TI  - Can a modified esophageal stent be useful in the treatment of nonresponsive
      benign colonic anastomotic stenosis?

PMID- 29041019
TI  - Endoscopic sleeve gastroplasty using Apollo Overstitch as a bridging procedure
      for superobese and high risk patients.

PMID- 29041020
TI  - [Pilot study on the effects and benefits of autologous fat grafting in
      osteoarthritis of the CMC-1 joint compared to intraarticular cortisone injection:
      results after 3 months].
AB  - Background/Aim Preliminary data suggest that an intraarticular autologous fat
      transplant may be useful in osteoarthritis (OA) of the CMC-1 joint. This
      prospective, non-randomised pilot study investigates this new method with a view
      to clinical outcomes compared with intraarticular corticosteroid injection.
      Patients and Methods 17 women and 7 men with an average age of 63.3 (47-75) years
      with symptomatic OA were included in the study. In 12 patients, a radiologically
      guided injection of 1-1.5 ml of adipose tissue was carried out after
      transumbilical liposuction of 10 ml of abdominal fat. Prior to that, the fat was
      homogenised using two Luer-Lock Syringes, but not centrifuged. Postoperatively,
      the thumb was immobilised for one week. The patients from the cortisone control
      group received an intraarticular injection of 10 mg (1 ml) of Triamcinolon(r)
      under sterile conditions without subsequent immobilisation. Preoperatively as
      well as 2, 6 and 12 weeks postoperatively, the QuickDASH and the Michigan-Hand
      Questionnaire (MHQ) were analysed, the pain was measured by means of the visual
      analogue scale (VAS), and strength and grip force were measured. Results Both the
      cortisone group and the autologous fat group showed a significant reduction in
      stress pain after two weeks. Both methods had no significant effect on force. The
      evaluation of quality of life by means of QuickDASH and MHQ after cortisone
      treatment initially demonstrated an improvement in quality of life, which,
      however, fell below the previous level after 6 weeks. After autologous fat
      transplantation, quality of life increased continuously. Conclusion In contrast
      to cortisone injection treatment, a persistent pain reduction was achieved in the
      fat injection group in the 3-month follow-up period, whereas cortisone injection
      only resulted in a short-term reduction of pain lasting about 6 weeks. Long-term
      follow-up is required now to show how long the effect of autologous fat
      transplantation in OA can be sustained.

PMID- 29041021
TI  - A comparison of outcomes of carpal tunnel release for carpal tunnel syndrome in
      patients diagnosed with and without electrophysiological studies.
AB  - Records were analysed from the institutional database, including 943 patients
      (1089 hands) with CTS who were operated on in the authors' department over a
      period of four years (2012 to 2015). The diagnosis of CTS was made solely on the
      basis of clinical findings in 551 patients (58 %); 392 patients (42 %) also had
      electrodiagnostic tests performed, for various reasons. Patients were followed-up
      at 1 and 6 months with assessments that included the Levine scores, filament
      tests, grip and pinch strength. No significant differences in Levine scores were
      found at the 1 and 6 month assessments. Statistically significant differences
      were noted in 3-point pinch strength and sensation: however, these were not
      clinically meaningful. The results of the study show that the results of carpal
      tunnel release in patients with typical symptoms are no better after
      electrodiagnostic tests.

PMID- 29041022
TI  - Multiple glomus tumours in multidigit nail bed.
AB  - Glomus tumours are lesions of the glomus body. A solitary glomus tumour is a more
      common, characteristically painful lesion, frequently located under the nail,
      whereas multiple glomus tumours are a rare clinical and genetic entity. Multiple
      glomus tumours are rarely subungual and do not show preference for any particular
      region of the body. We report a rare case of painful multidigit subungual glomus
      tumours in both hands.A 34-year-old male patient complained of painful fingertips
      (right: thumb, index finger, long finger, and ring finger; left: thumb, long
      finger, ring finger, small finger) on both hands for more than 5 years. Magnetic
      resonance imaging (MRI) detected multiple subungual glomus tumours in the
      fingertips (right long finger, ring finger, and left thumb, long, ring, and small
      finger) of both his hands, so the authors conducted tumour resection and sent
      biopsies for relevant fingers. We found the glomus tumour underneath the nail bed
      and achieved final diagnosis with histological confirmation. No remnant or newly
      developed lesion was detected at the 1 year outpatient clinic.Our case differed
      from the usual multiple glomus tumours because its characteristics were similar
      to those of a solitary glomus tumour, including the classic symptom triad: severe
      pain, localised pain, and cold hypersensitivity. In case report, we suggest the
      possibility that multidigit subungual glomus tumour is different from the common
      single subungual glomus tumour.

PMID- 29041023
TI  - [Bilateral, giant schwannoma of the ulnar nerve in a case of schwannomatosis].

PMID- 29041024
TI  - [Scar contracture with hyperextension in the wrist due to extravasation in the
      childhood - two-stage scar correction with the dermal regeneration template
      (Integra(r)) and skin graft].

PMID- 29041025
TI  - [Unsuccessful thumb replantation distal of an arteriovenous fistula].

PMID- 29041026
TI  - [Toxic Shock Syndrome caused by Fingertip Injury Management with semi-occlusive
      Dressing].

PMID- 29041027
TI  - [Late sequelae of a stab injury in the forearm with incorporation of a foreign
      body].

PMID- 29041028
TI  - [A rarity in handsurgery treatment: The injury of the hand by weever fish].

PMID- 29041029
TI  - ?

PMID- 29041030
TI  - ?

PMID- 29041031
TI  - Preliminary Experience with a Novel System of Facet Fixation to Treat Patients
      with Lumbar Degenerative Disease. A New Perspective in Minimally Invasive Spine
      Surgery?
AB  - PURPOSE:  We report our experience with a novel surgical device for the treatment
      of lumbar degenerative microinstability. Facet Wedge (DePuy Synthes, Raynham,
      Massachusetts, United States) is a novel technique of intra-articular lumbar
      facet fixation that provides a minimally invasive alternative to standard
      posterior fixation. MATERIALS AND METHODS:  From November 2014 to July 2015, 38
      patients underwent single-level Facet Wedge implantation. The main surgical
      indications included herniated disk (18 patients), spinal canal and foraminal
      stenosis (14 patients), and Meyerding grade I degenerative spondylolisthesis (6
      patients). All the patients showed radiologic signs of microinstability:
      hyperintensity in both facet joints (facet fluid signal) in T2-weighted magnetic
      resonance imaging and a black disk as a sign of degenerative disease. No slippage
      was evident at dynamic radiograph. After a period of conservative treatment
      (minimum of 6 months), surgery was performed. All patients' follow-up lasted over
      at least 12 months. RESULTS:  The low back visual analog scale score decreased
      significantly after surgery (from an average of 8.2 to 3.1 at final follow-up).
      Postoperatively, the Oswestry Disability Index showed a significant reduction
      (14.7 on average). No slippage or signs of adjacent segment degeneration was
      detected in neuroimaging follow-up. CONCLUSION:  Facet Wedge allows facet
      fixation in lumbar degenerative microinstability. To the best of our knowledge,
      this is the first clinical series reported in the literature on this novel
      device.

PMID- 29041032
TI  - Assessing the Structural Footprint of Minimally Invasive Brain Cannulation on
      Cerebral White Matter: A Cadaveric Model.
AB  - BACKGROUND:  All brain surgery requires some degree of iatrogenic trauma to
      healthy tissue. Minimally invasive approaches to brain tumors offer the potential
      of decreasing this trauma compared with conventional approaches. However, there
      are no validated radiologic models to examine axonal damage after minimally
      invasive entry into the brain. OBJECTIVE:  To present a cadaveric model of brain
      cannulation using fractional anisotropy measurements obtained from diffusion
      tensor magnetic resonance imaging (MRI). Two different methods of access are
      compared. METHODS:  Freshly harvested unfixed cadaveric brains were cannulated
      using both direct and indirect (i.e., dilation followed by cannulation) methods.
      Specimens were subjected to 68-direction diffusion tensor imaging scans and
      proton-density imaging. Fractional anisotropy (FA) data from a region of interest
      surrounding the entry zone was extracted from scans using imaging software and
      analyzed. RESULTS:  FA values were significantly higher following indirect
      cannulation (less invasive method) than they were following direct cannulation.
      FA values for undisturbed brain were significantly higher than in either of the
      cannulated groups, suggesting an inverse relationship between FA values and brain
      injury. CONCLUSION:  Axonal damage following brain cannulation can potentially be
      evaluated by FA analysis in a cadaveric model. These data may lead to an MRI
      based model of iatrogenic brain injury following tumor surgery. Future studies
      will focus on histologic analysis and clinical validation in live tissues.

PMID- 29041033
TI  - Portopulmonary Hypertension.

PMID- 29041035
TI  - Atmospheric extinction coefficient retrieval and validation for the single-band
      Mie-scattering Scheimpflug lidar technique.
AB  - An 808 nm single-band Mie scattering Scheimpflug lidar system is developed in
      Dalian, Northern China, for real-time, large-area atmospheric aerosol/particle
      remote sensing. Atmospheric measurement has been performed in urban area during a
      typical haze weather condition, and time-range distribution of atmospheric
      backscattering signal is recorded from March 18th to 22nd, 2017, by employing the
      Scheimpflug lidar system. Atmospheric extinction coefficient is then retrieved
      according to the Klett-inversion algorithm, while the boundary value is obtained
      by the slope-method in the far end where the atmosphere is homogeneous in a
      subinterval region. The correlation between the extinction coefficients retrieved
      from the Scheimpflug lidar technique and the PM10/PM2.5 concentrations measured
      by a conventional air pollution monitoring station is also studied. The good
      agreement between the measurement results, i.e., a correlation coefficient of
      0.85, successfully demonstrates the feasibility and great potential of the
      Scheimpflug lidar technique for atmospheric studies and applications.

PMID- 29041034
TI  - Inhaled versus systemic corticosteroids for preventing bronchopulmonary dysplasia
      in ventilated very low birth weight preterm neonates.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) remains an important cause of
      mortality and morbidity in preterm infants and inflammation plays a significant
      role in its pathogenesis. The use of inhaled corticosteroids may modulate the
      inflammatory process without concomitant high systemic steroid concentrations and
      less risk of adverse effects. This is an update of a review published in 2012
      (Shah 2012). We recently updated the related review on "Inhaled versus systemic
      corticosteroids for treating bronchopulmonary dysplasia in ventilated very low
      birth weight preterm neonates". OBJECTIVES: To determine the effect of inhaled
      versus systemic corticosteroids started within the first 7 days of life on
      preventing death or BPD in ventilated very low birth weight infants. SEARCH
      METHODS: We used the standard search strategy of Cochrane Neonatal to search the
      Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 1), MEDLINE
      via PubMed (1966 to 23 February 2017), Embase (1980 to 23 February 2017), and
      CINAHL (1982 to 23 February 2017). We searched clinical trials registers,
      conference proceedings and the reference lists of retrieved articles for
      randomised controlled trials (RCTs) and quasi-randomised trials. SELECTION
      CRITERIA: Randomised or quasi-randomised controlled trials comparing inhaled
      versus systemic corticosteroid therapy (irrespective of dose and duration)
      starting in the first seven days of life in very low birth weight preterm infants
      receiving assisted ventilation. DATA COLLECTION AND ANALYSIS: Clinical outcomes
      data were extracted and analysed using Review Manager. When appropriate, meta
      analysis was performed using typical relative risk (RR), typical risk difference
      (RD) and weighted mean difference (WMD). Meta-analyses were performed using
      typical relative risk, typical risk difference (RD), and weighted mean difference
      with their 95% confidence intervals (CI). If RD was statistically significant,
      the number needed to benefit or the number needed to harm was calculated. We
      assessed the quality of evidence was evaluated using GRADE principles. MAIN
      RESULTS: We included two trials that involved 294 infants. No new studies were
      included for the 2017 update. The incidence of death or BPD at 36 weeks'
      postmenstrual age was not statistically significantly different between infants
      who received inhaled or systemic steroids (RR 1.09, 95% CI 0.88 to 1.35; RD 0.05,
      95% CI -0.07 to 0.16; 1 trial, N = 278). The incidence of BPD at 36 weeks'
      postmenstrual age among survivors was not statistically significant between
      groups (RR 1.34, 95% CI 0.94 to 1.90; RD 0.11, 95% CI -0.02 to 0.24; 1 trial, N =
      206). There was no statistically significant difference in the outcomes of BPD at
      28 days, death at 28 days or 36 weeks' postmenstrual age and the combined outcome
      of death or BPD by 28 days between groups (2 trials, N = 294). The duration of
      mechanical ventilation was significantly longer in the inhaled steroid group
      compared with the systemic steroid group (typical MD 4 days, 95% CI 0.2 to 8; 2
      trials, N = 294; I2 = 0%) as was the duration of supplemental oxygen (typical MD
      11 days, 95% CI 2 to 20; 2 trials, N = 294; I2 = 33%).The incidence of
      hyperglycaemia was significantly lower with inhaled steroids (RR 0.52, 95% CI
      0.39 to 0.71; RD -0.25, 95% CI -0.37 to -0.14; 1 trial, N = 278; NNTB 4, 95% CI 3
      to 7 to avoid 1 infant experiencing hyperglycaemia). The rate of patent ductus
      arteriosus increased in the group receiving inhaled steroids (RR 1.64, 95% CI
      1.23 to 2.17; RD 0.21, 95% CI 0.10 to 0.33; 1 trial, N = 278; NNTH 5, 95% CI 3 to
      10). In a subset of surviving infants in the United Kingdom and Ireland there
      were no significant differences in developmental outcomes at 7 years of age.
      However, there was a reduced risk of having ever been diagnosed as asthmatic by 7
      years of age in the inhaled steroid group compared with the systemic steroid
      group (N = 48) (RR 0.42, 95% CI 0.19 to 0.94; RD -0.31, 95% CI -0.58 to -0.05;
      NNTB 3, 95% CI 2 to 20).According to GRADE the quality of the evidence was
      moderate to low. Evidence was downgraded on the basis of design (risk of bias),
      consistency (heterogeneity) and precision of the estimates.Both studies received
      grant support and the industry provided aero chambers and metered dose inhalers
      of budesonide and placebo for the larger study. No conflict of interest was
      identified. AUTHORS' CONCLUSIONS: We found no evidence that early inhaled
      steroids confer important advantages over systemic steroids in the management of
      ventilator-dependent preterm infants. Based on this review inhaled steroids
      cannot be recommended over systemic steroids as a part of standard practice for
      ventilated preterm infants. Because they might have fewer adverse effects than
      systemic steroids, further randomised controlled trials of inhaled steroids are
      needed that address risk/benefit ratio of different delivery techniques, dosing
      schedules and long-term effects, with particular attention to neurodevelopmental
      outcome.

PMID- 29041036
TI  - Electrical determination of current injection and internal quantum efficiencies
      in AlGaN-based deep-ultraviolet light-emitting diodes.
AB  - We propose a method to determine the current injection efficiency (CIE) and
      internal quantum efficiency (IQE) of light-emitting diodes (LEDs) during current
      injection. The method is based on fourth-order polynomial fitting of a modified
      rate equation to electroluminescence data. Our method can extract the CIE at low
      injection current densities, unlike conventional methods that generally assume
      the CIE to be unity. We apply the method to AlGaN-based deep-ultraviolet LEDs.
      Results show that the CIE was only approximately 51% at low injection current
      densities and was almost independent of injection current density up to 100
      A/cm2. The peak IQE was 77%.

PMID- 29041037
TI  - Fast yet accurate computation of radiances in shortwave infrared satellite remote
      sensing channels.
AB  - Accurate radiative transfer simulations of signals received by sensors deployed
      on satellite platforms for remote sensing purposes can be computationally
      demanding depending on channel width and the spectral variation of atmospheric
      and surface optical properties. Therefore, methods that can speed up such
      simulations are desirable. While it is common practice to use atmospheric
      "window" channels to minimize the influence of gaseous absorption, the impact of
      the underlying surface as well as clouds and aerosols has received less
      attention. To reduce the number of monochromatic computations required to obtain
      a desired accuracy, one may average the inherent optical properties (IOPs) over a
      spectral band to generate effective or mean IOP values to be used in "quasi
      monochromatic" radiative transfer computations. Comparison of radiances produced
      by computations based on mean (quasi-monochromatic) IOPs with benchmark results
      in typical shortwave infrared window channels, revealed that while this approach
      may be sufficient for gaseous absorption, it led to significant errors in the
      presence spectrally varying surface IOPs, in general, and snow/ice surfaces, in
      particular. To solve this problem, a new method was developed in which a
      satellite channel is represented by a few subbands. This new method significantly
      reduces the error resulting from IOP averaging to be typically less than 1%. An
      additional correction was also developed to further reduce the error incurred by
      use of mean gas IOPs for large solar zenith angles to be less than 0.01%.

PMID- 29041038
TI  - Optical analysis of a III-V-nanowire-array-on-Si dual junction solar cell.
AB  - A tandem solar cell consisting of a III-V nanowire subcell on top of a planar Si
      subcell is a promising candidate for next generation photovoltaics due to the
      potential for high efficiency. However, for success with such applications, the
      geometry of the system must be optimized for absorption of sunlight. Here, we
      consider this absorption through optics modeling. Similarly, as for a bulk dual
      junction tandem system on a silicon bottom cell, a bandgap of approximately 1.7
      eV is optimum for the nanowire top cell. First, we consider a simplified system
      of bare, uncoated III-V nanowires on the silicon substrate and optimize the
      absorption in the nanowires. We find that an optimum absorption in 2000 nm long
      nanowires is reached for a dense array of approximately 15 nanowires per square
      micrometer. However, when we coat such an array with a conformal indium tin oxide
      (ITO) top contact layer, a substantial absorption loss occurs in the ITO. This
      ITO could absorb 37% of the low energy photons intended for the silicon subcell.
      By moving to a design with a 50 nm thick, planarized ITO top layer, we can reduce
      this ITO absorption to 5%. However, such a planarized design introduces
      additional reflection losses. We show that these reflection losses can be reduced
      with a 100 nm thick SiO2 anti-reflection coating on top of the ITO layer. When we
      at the same time include a Si3N4 layer with a thickness of 90 nm on the silicon
      surface between the nanowires, we can reduce the average reflection loss of the
      silicon cell from 17% to 4%. Finally, we show that different approximate models
      for the absorption in the silicon substrate can lead to a 15% variation in the
      estimated photocurrent density in the silicon subcell.

PMID- 29041039
TI  - Direct-comb molecular spectroscopy by heterodyne detection with continuous-wave
      laser for high sensitivity.
AB  - We have demonstrated direct-comb molecular spectroscopy in which an individual
      comb mode is resolved by heterodyne detection with a continuous-wave (cw) laser.
      This simple, fast, and sensitive technique was demonstrated for atomic
      spectroscopy in [ Appl. Phys. Lett.101, 051105 ( 2012)], but is more suitable for
      molecular spectroscopy. Four rotation-vibration transitions of methane have
      simultaneously been recorded in a Doppler-limited resolution using a spectrally
      broadened comb based on an Er-doped fiber laser and a cw 1651-nm distributed
      feedback laser diode. Even though the power level of the comb modes and the
      sample absorption are weaker than those of the previous studies, in this work the
      cw laser frequency is stabilized to one of the comb modes, and the data are
      thereby averaged for extended periods of time, resulting an improvement in
      sensitivity.

PMID- 29041040
TI  - Water-leaving contribution to polarized radiation field over ocean.
AB  - The top-of-atmosphere (TOA) radiation field from a coupled atmosphere-ocean
      system (CAOS) includes contributions from the atmosphere, surface, and water
      body. Atmospheric correction of ocean color imagery is to retrieve water-leaving
      radiance from the TOA measurement, from which ocean bio-optical properties can be
      obtained. Knowledge of the absolute and relative magnitudes of water-leaving
      signal in the TOA radiation field is important for designing new atmospheric
      correction algorithms and developing retrieval algorithms for new ocean
      biogeochemical parameters. In this paper we present a systematic sensitivity
      study of water-leaving contribution to the TOA radiation field, from 340 nm to
      865 nm, with polarization included. Ocean water inherent optical properties are
      derived from bio-optical models for two kinds of waters, one dominated by
      phytoplankton (PDW) and the other by non-algae particles (NDW). In addition to
      elastic scattering, Raman scattering and fluorescence from dissolved organic
      matter in ocean waters are included. Our sensitivity study shows that the
      polarized reflectance is minimized for both CAOS and ocean signals in the
      backscattering half plane, which leads to numerical instability when calculating
      water leaving relative contribution, the ratio between polarized water leaving
      and CAOS signals. If the backscattering plane is excluded, the water-leaving
      polarized signal contributes less than 9% to the TOA polarized reflectance for
      PDW in the whole spectra. For NDW, the polarized water leaving contribution can
      be as much as 20% in the wavelength range from 470 to 670 nm. For wavelengths
      shorter than 452 nm or longer than 865 nm, the water leaving contribution to the
      TOA polarized reflectance is in general smaller than 5% for NDW. For the TOA
      total reflectance, the water-leaving contribution has maximum values ranging from
      7% to 16% at variable wavelengths from 400 nm to 550 nm from PDW. The water
      leaving contribution to the TOA total reflectance can be as large as 35% for NDW,
      which is in general peaked at 550 nm. Both the total and polarized reflectances
      from water-leaving contributions approach zero in the ultraviolet and near
      infrared bands. These facts can be used as constraints or guidelines when
      estimating the water leaving contribution to the TOA reflectance for new
      atmospheric correction algorithms for ocean color imagery.

PMID- 29041041
TI  - Frequency response of the external quantum efficiency in multijunction solar
      cells.
AB  - The frequency dependence of the external quantum efficiency (EQE) of high-quality
      multijunction solar cells was examined by the modulated photocurrent spectroscopy
      method via an optical setup comprised of a light-pipe-coupled compact LED array.
      The optical excitation was achieved through sinusoidal electrical modulation of
      an appropriate LED by a custom-designed, high bandwidth amplifier. We observed
      unique features in the amplitude and phase data of the EQE frequency sweeps that
      are very sensitive to various subcell parameters and light bias conditions. These
      features are discussed extensively within the context of an AC equivalent circuit
      model, showing remarkable agreement between the experimental data and the
      proposed model.

PMID- 29041042
TI  - Responses transition in a monolayer Al-Al2O3 nanoparticle-crystal due to
      oxidation.
AB  - Nanoparticle is a promising candidate for large scale fabrication of
      metamaterial. However, optical responses for metamaterial made of abound metal
      like Al can be thoroughly changed due to oxidization. Especially for nanoparticle
      whose aspect ratio is extremely high, oxidation usually occurs. So to understand
      how the responses shift in a nanoparticle system due to oxidization is essential
      for large scale application of metamaterial. In this paper, we have concluded and
      quantified two general principles describing this transition in a monolayer Al
      Al2O3 nanoparticle-crystal, which can be used in a thermophotovoltaic system.
      Square pattern, in which the unit of changing crystal is a square cell made up of
      Al and Al2O3 particles, is firstly demonstrated. A double oscillators model has
      been proposed to understand the interference between different absorption modes
      and their coupling. Using near-field distribution, equivalent inductor-capacitor
      model and dispersion relationship of surface Plasmon polariton, we have
      distinguished the resonance modes, concluded the transition principles in a
      simple case. Then the two principles are applied in a larger cell to verify its
      university. After detailed demonstration of symmetric square pattern, models and
      principles are extrapolated to more complex non-symmetric systems. The basic
      understanding gained here will help the design of robust large-scale
      metamaterial.

PMID- 29041043
TI  - Validation of a spectral correction procedure for sun and sky reflections in
      above-water reflectance measurements.
AB  - A three-component reflectance model (3C) is applied to above-water radiometric
      measurements to derive remote-sensing reflectance Rrs (lambda). 3C provides a
      spectrally resolved offset Delta(lambda) to correct for residual sun and sky
      radiance (Rayleigh- and aerosol-scattered) reflections on the water surface that
      were not represented by sky radiance measurements. 3C is validated with a data
      set of matching above- and below-water radiometric measurements collected in the
      Baltic Sea, and compared against a scalar offset correction Delta. Correction
      with Delta(lambda) instead of Delta consistently reduced the (mean normalized
      root-mean-square) deviation between Rrs (lambda) and reference reflectances to
      comparable levels for clear (Delta: 14.3 +/- 2.5 %, Delta(lambda): 8.2 +/- 1.7
      %), partly clouded (Delta: 15.4 +/- 2.1 %, Delta(lambda): 6.5 +/- 1.4 %), and
      completely overcast (Delta: 10.8 +/- 1.7 %, Delta(lambda): 6.3 +/- 1.8 %) sky
      conditions. The improvement was most pronounced under inhomogeneous sky
      conditions when measurements of sky radiance tend to be less representative of
      surface-reflected radiance. Accounting for both sun glint and sky reflections
      also relaxes constraints on measurement geometry, which was demonstrated based on
      a semi-continuous daytime data set recorded in a eutrophic freshwater lake in the
      Netherlands. Rrs (lambda) that were derived throughout the day varied spectrally
      by less than 2 % relative standard deviation. Implications on measurement
      protocols are discussed. An open source software library for processing
      reflectance measurements was developed and is made publicly available.

PMID- 29041044
TI  - Novel method for quantitative and real-time measurements on engine combustion at
      varying pressure based on the wavelength modulation spectroscopy.
AB  - The wavelength modulation spectroscopy (WMS) technique has been demonstrated as a
      powerful and indispensable tool for quantitative and real-time measurements on
      the combustion process of various industrial devices. However, the varying
      pressure occurred in the aero-engine combustor significantly affects the accuracy
      and efficiency of the WMS technique. To address this issue, this work reports a
      novel method named WMS pressure correction model, which can enable fast signal
      processing in the measurements at varying pressure. The method was first
      validated in a heated optical cell, and then applied to the pressure and
      temperature measurements in an aero-engine combustor. The results show that the
      new method can efficiently and accurately measure the pressure and temperature at
      the varying pressure conditions.

PMID- 29041045
TI  - Monolithic stacked blue light-emitting diodes with polarization-enhanced tunnel
      junctions.
AB  - Monolithic stacked InGaN light-emitting diode (LED) connected by a polarization
      enhanced GaN/AlN-based tunnel junction is demonstrated experimentally in this
      study. The typical stacked LEDs exhibit 80% enhancement in output power compared
      with conventional single LEDs because of the repeated use of electrons and holes
      for photon generation. The typical operation voltage of stacked LEDs is higher
      than twice the operation voltage of single LEDs. This high operation voltage can
      be attributed to the non-optimal tunneling junction in stacked LEDs. In addition
      to the analyses of experimental results, theoretical analysis of different
      schemes of tunnel junctions, including diagrams of energy bands, diagrams of
      electric fields, and current-voltage relation curves, are investigated using
      numerical simulation. The results shown in this paper demonstrate the feasibility
      in developing cost-effective and highly efficient tunnel-junction LEDs.

PMID- 29041046
TI  - Determining the optimal spectral sampling frequency and uncertainty thresholds
      for hyperspectral remote sensing of ocean color.
AB  - Using a modified geostatistical technique, empirical variograms were constructed
      from the first derivative of several diverse Remote Sensing Reflectance and
      Phytoplankton Absorbance spectra to describe how data points are correlated with
      "distance" across the spectra. The maximum rate of information gain is measured
      as a function of the kurtosis associated with the Gaussian structure of the
      output, and is determined for discrete segments of spectra obtained from a
      variety of water types (turbid river filaments, coastal waters, shelf waters, a
      dense Microcystis bloom, and oligotrophic waters), as well as individual and
      mixed phytoplankton functional types (PFTs; diatoms, eustigmatophytes,
      cyanobacteria, coccolithophores). Results show that a continuous spectrum of 5 to
      7 nm spectral resolution is optimal to resolve the variability across mixed
      reflectance and absorbance spectra. In addition, the impact of uncertainty on
      subsequent derivative analysis is assessed, showing that a 3% Gaussian noise (SNR
      ~66) addition compromises data quality without smoothing the spectrum, and a 13%
      noise (SNR ~15) addition compromises data with smoothing.

PMID- 29041047
TI  - Impact of spectral resolution of in situ ocean color radiometric data in
      satellite matchups analyses.
AB  - The spectral resolution requirements for in situ remote sensing reflectanceRRS
      measurements aiming at supporting satellite ocean color validation and System
      Vicarious Calibration (SVC) were investigated. The study, conducted using sample
      hyperspectral RRS from different water types, focused on the visible spectral
      bands of the ocean land color imager (OLCI) and of the Plankton, Aerosol, Cloud,
      ocean Ecosystem (PACE) satellite sensors. Allowing for a +/-0.5% maximum
      difference between in situ and satellite derived RRS solely due to the spectral
      band characteristics of the in situ radiometer, a spectral resolution of 1 nm for
      SVC of PACE is needed in oligotrophic waters. Requirements decrease to 3 nm for
      SVC of OLCI. In the case of validation activities, which exhibit less stringent
      uncertainty requirements with respect to SVC, a maximum difference of +/-1%
      between in situ and satellite derived data indicates the need for a spectral
      resolution of 3 nm for both OLCI and PACE in oligotrophic waters. Conversely,
      spectral resolutions of 6 nm for PACE and 9 nm for OLCI appear to satisfy
      validation activities in optically complex waters.

PMID- 29041048
TI  - Studying aerosol light scattering based on aspect ratio distribution observed by
      fluorescence microscope.
AB  - Particle shape is crucial to the properties of light scattered by atmospheric
      aerosol particles. A method of fluorescence microscopy direct observation was
      introduced to determine the aspect ratio distribution of aerosol particles. The
      result is comparable with that of the electron microscopic analysis. The measured
      aspect ratio distribution has been successfully applied in modeling light
      scattering and further in simulation of polarization measurements of the sun/sky
      radiometer. These efforts are expected to improve shape retrieval from skylight
      polarization by using directly measured aspect ratio distribution.

PMID- 29041049
TI  - Full-spectrum light management by pseudo-disordered moth-eye structures for thin
      film solar cells.
AB  - In this paper, the role of pseudo-disordered moth-eye structures on the optical
      features for application to thin-film solar cells is investigated to realize the
      superior light management for the full-spectrum solar energy utilization,
      compared with some ordered structures. Without loss of generality, the c-Si thin
      film solar cell is taken as the example. The results demonstrate that the
      fluctuations introduced into the geometry parameters of moth-eye elements can
      lead to the remarkable absorption enhancement in the wavelength region of 0.3-1.1
      MUm and high transmission in the wavelength range of 1.1-2.5 MUm. Two mechanisms
      including the increasing spectral density of modes and the intensive
      forescattering intensity are identified to be responsible for the absorption
      enhancement. In addition, the optical characteristics of the moth-eye surface
      with both disordered height and disordered diameter are insensitive to the
      incident angle.

PMID- 29041050
TI  - Floating-base germanium-tin heterojunction phototransistor for high-efficiency
      photodetection in short-wave infrared range.
AB  - The floating-base germanium-tin (Ge1-xSnx) heterojunction phototransistor (HPT)
      is designed and investigated as an efficient optical receiver in the short-wave
      infrared range. Simulations indicate that as the Sn content increases, the
      responsivity significantly increases due to a higher absorption coefficient and a
      larger valence band offset between Ge and Ge1-xSnx. Ge0.935Sn0.065 HPTs that
      incorporated high-quality Ge0.935Sn0.065 film grown by molecular beam epitaxy
      were fabricated, demonstrating optical response beyond wavelength of 2003 nm. At
      a low bias voltage of 1.0 V, optical response enhancement of ~10 times was
      achieved over the conventional Ge0.935Sn0.065 p-i-n photodiode. High
      responsivities of ~1.8 A/W at 1550 nm and ~0.043 A/W at 2003 nm were demonstrated
      with low dark current density of 0.147 A/cm2.

PMID- 29041051
TI  - Systematic characterization and optimization of 3D light field displays.
AB  - One of the key issues in conventional stereoscopic displays is the well-known
      vergence-accommodation conflict problem due to the lack of the ability to render
      correct focus cues for 3D scenes. Recently several light field display methods
      have been explored to reconstruct a true 3D scene by sampling either the
      projections of the 3D scene at different depths or the directions of the light
      rays apparently emitted by the 3D scene and viewed from different eye positions.
      These methods are potentially capable of rendering correct or nearly correct
      focus cues and addressing the vergence-accommodation conflict problem. In this
      paper, we describe a generalized framework to model the image formation process
      of the existing light-field display methods and present a systematic method to
      simulate and characterize the retinal image and the accommodation response
      rendered by a light field display. We further employ this framework to
      investigate the trade-offs and guidelines for an optimal 3D light field display
      design. Our method is based on quantitatively evaluating the modulation transfer
      functions of the perceived retinal image of a light field display by accounting
      for the ocular factors of the human visual system.

PMID- 29041052
TI  - Thin-film camera using luminescent concentrators and an optical Soller
      collimator.
AB  - This article reports our investigation of the potential of optical Soller
      collimators in combination with luminescent concentrators for lens-less, short
      distance, and shape-independent thin-film imaging. We discuss optical imaging
      capabilities and limitations, and present first prototypes and results. Modern 3D
      laser lithography and deep X-ray lithography support the manufacturing of
      extremely fine collimator structures that pave the way for flexible and scalable
      thin-film cameras that are far thinner than 1 mm (including optical imaging and
      color sensor layers).

PMID- 29041053
TI  - Organic membrane photonic integrated circuits (OMPICs).
AB  - We propose the concept of organic membrane photonic integrated circuits (OMPICs),
      which incorporate various functions needed for optical signal processing into a
      flexible organic membrane. We describe the structure of several devices used
      within the proposed OMPICs (e.g., transmission lines, I/O couplers, phase
      shifters, photodetectors, modulators), and theoretically investigate their
      characteristics. We then present a method of fabricating the photonic devices
      monolithically in an organic membrane and demonstrate the operation of
      transmission lines and I/O couplers, the most basic elements of OMPICs.

PMID- 29041054
TI  - Failure prediction using machine learning and time series in optical network.
AB  - In this paper, we propose a performance monitoring and failure prediction method
      in optical networks based on machine learning. The primary algorithms of this
      method are the support vector machine (SVM) and double exponential smoothing
      (DES). With a focus on risk-aware models in optical networks, the proposed
      protection plan primarily investigates how to predict the risk of an equipment
      failure. To the best of our knowledge, this important problem has not yet been
      fully considered. Experimental results showed that the average prediction
      accuracy of our method was 95% when predicting the optical equipment failure
      state. This finding means that our method can forecast an equipment failure risk
      with high accuracy. Therefore, our proposed DES-SVM method can effectively
      improve traditional risk-aware models to protect services from possible failures
      and enhance the optical network stability.

PMID- 29041055
TI  - Fano resonances in plasmonic heptamer nano-hole arrays.
AB  - The optical properties of gold heptamer nanohole arrays have been investigated
      theoretically and numerically. This structure support pronounced Fano resonances
      with high transmittance (~50%) and narrow bandwidths (down to 12 nm). The Fano
      features arise from the interference between light directly transmitted through
      the holes, and light indirectly scattered through the excitation of localized
      surface plasmon polaritons (LSPPs), propagating surface plasmon polaritons
      (SPPs), or/and waves related to Wood's anomaly (WA). The mechanisms behind the
      generation of these resonances are revealed by observing near-field
      distributions, altering the structural parameters and applying the Bloch wave
      model. Furthermore, it is shown that Fano resonances associated with LSPPs
      exhibit high surface (2 nm/nm) and bulk sensitivities (400 nm/RIU). However, the
      highest figure of merit (~24 RIU-1) occurs for a Fano resonance involving a WA
      and SPP mode.

PMID- 29041056
TI  - Fault-tolerant distribution of GHZ states and controlled DSQC based on parity
      analyses.
AB  - Based on the circuit including linear optical elements, a fault-tolerant
      distribution of GHZ states against collective noise among three parties is
      proposed. Additionally, two controlled DSQC protocols using the shared GHZ states
      as quantum channels are also presented under the charge of the controller. The
      first controlled DSQC protocol applies single parity analysis based on weak cross
      Kerr nonlinearities. The receiver Bob performs single-photon measurement to
      obtain the secret information after the outcome publication of the single parity
      analysis executed by the sender Alice. The second protocol applies dense coding
      to double information transmission capacity, and the double parity analyses based
      on weak cross-Kerr nonlinearities are performed to obtain the secret information.

PMID- 29041057
TI  - Dual comb generation from a mode-locked fiber laser with orthogonally polarized
      interlaced pulses.
AB  - Ultra-high precision dual-comb spectroscopy traditionally requires two mode
      locked, fully stabilized lasers with complex feedback electronics. We present a
      novel mode-locked operation regime in a thulium-holmium co-doped fiber laser, a
      frequency-halved state with orthogonally polarized interlaced pulses, for dual
      comb generation from a single source. In a linear fiber laser cavity, an
      ultrafast pulse train composed of co-generated, equal intensity and orthogonally
      polarized consecutive pulses at half of the fundamental repetition rate is
      demonstrated based on vector solitons. Upon optical interference of the
      orthogonally polarized pulse trains, two stable microwave RF beat combs are
      formed, effectively down-converting the optical properties into the microwave
      regime. These co-generated, dual polarization interlaced pulse trains, from one
      all-fiber laser configuration with common mode suppression, thus provide an
      attractive compact source for dual-comb spectroscopy, optical metrology and
      polarization entanglement measurements.

PMID- 29041058
TI  - Enhancement of the second plateau in solid high-order harmonic spectra by the two
      color fields.
AB  - We theoretically investigate high-order harmonic generation (HHG) from solids in
      two-color fields. It is found that under the premise of maintaining the same
      amplitude, the intensity of the second plateau can be enhanced by two to three
      orders in a proper two-color field compared with the result in the monochromatic
      field with the same frequency as the driving pulse of the two-color field. This
      can be attributed to the fact that most excited electrons can be driven to the
      top of the first conduction band due to the larger vector potential of the two
      color fields, which leads to the higher electron population of upper conduction
      bands. Moreover, we also find that isolated attosecond pulses can be generated
      from solids by choosing a proper two-color field that allows the electrons to
      reach the top of the first conduction band only once. This work provides a
      promising method for extending the range of solid HHG spectra in experiments.

PMID- 29041059
TI  - Non-destructive analysis of flake properties in automotive paints with full-field
      optical coherence tomography and 3D segmentation.
AB  - Automotive coating systems are designed to protect vehicle bodies from corrosion
      and enhance their aesthetic value. The number, size and orientation of small
      metallic flakes in the base coat of the paint has a significant effect on the
      appearance of automotive bodies. It is important for quality assurance (QA) to be
      able to measure the properties of these small flakes, which are approximately
      10MUm in radius, yet current QA techniques are limited to measuring layer
      thickness. We design and develop a time-domain (TD) full-field (FF) optical
      coherence tomography (OCT) system to scan automotive panels volumetrically, non
      destructively and without contact. We develop and integrate a segmentation method
      to automatically distinguish flakes and allow measurement of their properties. We
      test our integrated system on nine sections of five panels and demonstrate that
      this integrated approach can characterise small flakes in automotive coating
      systems in 3D, calculating the number, size and orientation accurately and
      consistently. This has the potential to significantly impact QA testing in the
      automotive industry.

PMID- 29041060
TI  - Optimizing single-mode collection from pointlike sources of single photons with
      adaptive optics.
AB  - The collection efficiency of light from a point-like emitter may be extremely
      poor due to aberrations induced by collection optics and the emission
      distribution of the source. Analyzing the aberrant wavefront (e.g., with a Shack
      Hartmann sensor) and correcting accordingly can be infeasible on the single
      photon level. We present a technique that uses a genetic algorithm to control a
      deformable mirror for correcting wavefront aberrations in single-photon signals
      from point emitters. We apply our technique to both a simulated point source and
      a real InAs quantum dot, achieving coupling increases of up to 50% and automatic
      reduction of system drift.

PMID- 29041061
TI  - Novel configuration for an enhanced and compact all-fiber Faraday rotator with
      matched birefringence.
AB  - We propose a novel configuration for an improved and compact all fiber Faraday
      rotator based on phase matching between the Faraday rotation and bend-induced
      birefringence. The device utilizes a coiled fiber within two electro-magnetic
      toroids, such that the fiber length required for getting the beat length is quite
      long and several rounds of fiber are needed. Analysis of the capabilities of the
      proposed device and its sensitivity to different parameters is presented. Faraday
      rotation of 13 degrees  was experimentally measured in six meters of single mode
      silica fiber, with a magnetic field of about 0.06T at a wavelength of 1064nm. We
      show that phase matching between the two phenomena significantly improves the
      polarization rotation by a factor of 4-10. In addition, we demonstrate the
      ability to achieve higher rotation by using Fabry Perot resonator in low terbium
      doped glass.

PMID- 29041062
TI  - Studies on the sparsifying operator in compressive digital holography.
AB  - In compressive digital holography, we reconstruct sparse object wavefields from
      undersampled holograms by solving an l1-minimization problem. Applying wavelet
      transformations to the object wavefields produces the necessary sparse
      representations, but prior work clings to transformations with too few vanishing
      moments. We put several wavelet transformations belonging to different wavelet
      families to the test by evaluating their sparsifying properties, the number of
      hologram samples that are required to reconstruct the sparse wavefields
      perfectly, and the robustness of the reconstructions to additive noise and
      sparsity defects. In particular, we recommend the CDF 9/7 and 17/11 wavelet
      transformations, as well as their reverse counter-parts, because they yield
      sufficiently sparse representations for most accustomed wavefields in combination
      with robust reconstructions. These and other recommendations are procured from
      simulations and are validated using biased, noisy holograms.

PMID- 29041063
TI  - Efficient continuous wave and quasi-continuous wave operation of a 2.8 MUm
      Er:Lu2O3 ceramic laser.
AB  - We have demonstrated a highly efficient 2.8 MUm Er-doped Lu2O3 ceramic laser and
      investigated the lasing dynamics by time-resolved spectroscopy. During room
      temperature continuous wave operation, a slope efficiency of 22% was achieved
      with a high-quality transparent ceramic. To our knowledge, this is the highest
      slope efficiency obtained by an Er:Lu2O3 ceramic laser. In addition, an output
      peak power of 1.2 W was obtained during quasi-continuous wave operation. Time
      resolved spectroscopy showed that the emission wavelengths exhibited a red shift
      from 2715 to 2845 nm, which indicated that continuous wave operation may be
      possible at 2740 and 2845 nm.

PMID- 29041064
TI  - Signaling on the continuous spectrum of nonlinear optical fiber.
AB  - This paper studies different signaling techniques on the continuous spectrum (CS)
      of nonlinear optical fiber defined by nonlinear Fourier transform. Three
      different signaling techniques are proposed and analyzed based on the statistics
      of the noise added to CS after propagation along the nonlinear optical fiber. The
      proposed methods are compared in terms of error performance, distance reach, and
      complexity. Furthermore, the effect of chromatic dispersion on the data rate and
      noise in nonlinear spectral domain is investigated. It is demonstrated that, for
      a given sequence of CS symbols, an optimal bandwidth (or symbol rate) can be
      determined so that the temporal duration of the propagated signal at the end of
      the fiber is minimized. In effect, the required guard interval between the
      subsequently transmitted data packets in time is minimized and the effective data
      rate is significantly enhanced. Moreover, by selecting the proper signaling
      method and design criteria a distance reach of 7100 km is reported by only
      singling on CS at a rate of 9.6 Gbps.

PMID- 29041065
TI  - High-precision lateral distortion measurement and correction in coherence
      scanning interferometry using an arbitrary surface.
AB  - Lateral optical distortion is present in most optical imaging systems. In
      coherence scanning interferometry, distortion may cause field-dependent
      systematic errors in the measurement of surface topography. These errors become
      critical when high-precision surfaces, e.g. precision optics, are measured.
      Current calibration and correction methods for distortion require some form of
      calibration artefact that has a smooth local surface and a grid of high-precision
      manufactured features. Moreover, to ensure high accuracy and precision of the
      absolute and relative locations of the features of these artefacts, requires
      their positions to be determined using a traceable measuring instrument, e.g. a
      metrological atomic force microscope. Thus, the manufacturing and calibration
      processes for calibration artefacts are often expensive and complex. In this
      paper, we demonstrate for the first time the calibration and correction of
      optical distortion in a coherence scanning interferometer system by using an
      arbitrary surface that contains some deviations from flat and has some features
      (possibly just contamination), such that feature detection is possible. By using
      image processing and a self-calibration technique, a precision of a few
      nanometres is achieved for the distortion correction. An inexpensive metal
      surface, e.g. the surface of a coin, or a scratched and defected mirror, which
      can be easily found in a laboratory or workshop, may be used. The cost of the
      distortion correction with nanometre level precision is reduced to almost zero if
      the absolute scale is not required. Although an absolute scale is still needed to
      make the calibration traceable, the problem of obtaining the traceability is
      simplified as only a traceable measure of the distance between two arbitrary
      points is needed. Thus, the total cost of transferring the traceability may also
      be reduced significantly using the proposed method.

PMID- 29041066
TI  - All-fibre pseudo-slit reformatters.
AB  - We report two different types of all-fibre pseudo-slit reformatters made either
      by tapering bundles of single-mode fibres or by postprocessing a photonic crystal
      fibre. These devices convert the modes of a multimode core to the modes of a
      linear pseudo-slit output structure, achieving a diffraction limited pattern in
      one direction.

PMID- 29041067
TI  - Simple method for efficient reconfigurable optical vortex beam splitting.
AB  - In recent years, singular light beams with orbital angular momentum are one of
      the most striking examples of structured light that have been widely applied in
      modern science. The transition from the generation of a single vortex beam to the
      generation of multiple such beams progressed the development of singular optics.
      This paper presents a new efficient method of vortex laser beam splitting using a
      two-level pure-phase diffractive optical element. The proposed compact element,
      which can be easily implemented with a low-cost binary spatial light modulator or
      fabricated by electron beam lithography or photolithography, is a useful tool for
      the reconfigurable generation of multiple closed-packed vortex beams.
      Furthermore, the proposed splitter can efficiently operate in the wavelength
      range of approximately 8% of the central wavelength, thus providing an efficient
      method to generate optical vortex arrays with various potential applications in
      modern optics and photonics.

PMID- 29041068
TI  - Relativistic electron acceleration by mJ-class kHz lasers normally incident on
      liquid targets.
AB  - We report observation of kHz-pulsed-laser-accelerated electron energies up to 3
      MeV in the -klaser (backward) direction from a 3 mJ laser interacting at normal
      incidence with a solid density, flowing-liquid target. The electrons/MeV/s.r. >1
      MeV recorded here using a mJ-class laser exceeds or equals that of prior super
      ponderomotive electron studies employing lasers at lower repetition-rates and
      oblique incidence. Focal intensity of the 40-fs-duration laser is 1.5 . 1018 W cm
      2, corresponding to only ~80 keV electron ponderomotive energy. Varying laser
      intensity confirms electron energies in the laser-reflection direction well above
      what might be expected from ponderomotive scaling in normal-incidence laser
      target geometry. This direct, normal-incidence energy spectrum measurement is
      made possible by modifying the final focusing off-axis-paraboloid (OAP) mirror
      with a central hole that allows electrons to pass, and restoring laser intensity
      through adaptive optics. A Lanex-based, optics-free high-acquisition rate (>100
      Hz) magnetic electron-spectrometer was developed for this study to enable shot-to
      shot statistical analysis and real-time feedback, which was leveraged in finding
      optimal pre-plasma conditions. 3D Particle-in-cell simulations of the interaction
      show qualitative super-ponderomotive spectral agreement with experiment. The
      demonstration of a high-repetition-rate, high-flux source containing >MeV
      electrons from a few-mJ, 40 fs laser and a simple liquid target encourages
      development of future >=kHz-repetition, fs-duration electron-beam applications.

PMID- 29041069
TI  - Generation of vector dissipative and conventional solitons in large normal
      dispersion regime.
AB  - We report the generation of both polarization-locked vector dissipative soliton
      and group velocity-locked vector conventional soliton in a nanotube-mode-locked
      fiber ring laser with large normal dispersion, for the first time to our best
      knowledge. Depending on the polarization-depended extinction ratio of the fiber
      based Lyot filter, the two types of vector solitons can be switched by simply
      tuning the polarization controller. In the case of low filter extinction ratio,
      the output vector dissipative soliton exhibits steep spectral edges and strong
      frequency chirp, which presents a typical pulse duration of ~23.4 ps, and can be
      further compressed to ~0.9 ps. In the contrastive case of high filter extinction
      ratio, the vector conventional soliton has clear Kelly sidebands with transform
      limited pulse duration of ~1.8 ps. Our study provides a new and simple method to
      achieve two different vector soliton sources, which is attractive for potential
      applications requiring different pulse profiles.

PMID- 29041070
TI  - Design of metasurface polarizers based on two-dimensional cold atomic arrays.
AB  - Engineering light-matter interaction using cold atomic arrays is one of the
      central topics in modern optics. Here we have demonstrated the capability of two
      dimensional asymmetric cold atomic arrays as microscopic metasurfaces for
      controlling polarization states of light. The designed linear polarizer can lead
      to an extinction ratio over 20dB as well as a high transmittance over 0.8 for the
      permitted polarization at zero detuning. For detuned driving light, changing
      lattice constants can also achieve high performance linear polarizers. We have
      also accomplished a circular polarizer by manipulating the phases of transmitted
      light. A theoretical analysis based on Bloch theorem shows the underlying
      mechanism for this performance is actually attributed to cooperative effects in
      periodic lattices. Finally, we discuss in detail the effects of system size,
      lattice imperfection and nonzero driving light linewidth in practical
      implementation. The present study paves a way to design extremely miniaturized
      metasurfaces using cold atoms and other two-level systems, showing great
      potential in quantum information and quantum metrology sciences as well as the
      fundamental physics of light-matter interaction.

PMID- 29041071
TI  - Characterization of micron-size hydrogen clusters using Mie scattering.
AB  - Hydrogen clusters with diameters of a few micrometer range, composed of 108-10
      hydrogen molecules, have been produced for the first time in an expansion of
      supercooled, high-pressure hydrogen gas into a vacuum through a conical nozzle
      connected to a cryogenic pulsed solenoid valve. The size distribution of the
      clusters has been evaluated by measuring the angular distribution of laser light
      scattered from the clusters. The data were analyzed based on the Mie scattering
      theory combined with the Tikhonov regularization method including the
      instrumental functions, the validity of which was assessed by performing a
      calibration study using a reference target consisting of standard micro-particles
      with two different sizes. The size distribution of the clusters was found
      discrete peaked at 0.33 +/- 0.03, 0.65 +/- 0.05, 0.81 +/- 0.06, 1.40 +/- 0.06 and
      2.00 +/- 0.13 um in diameter. The highly reproducible and impurity-free nature of
      the micron-size hydrogen clusters can be a promising target for laser-driven
      multi-MeV proton sources with the currently available high power lasers.

PMID- 29041072
TI  - Magnetic modulation of mid-infrared plasmons using Giant Magnetoresistance.
AB  - We propose a novel approach to generate active mid IR plasmonic systems by
      incorporating giant magnetoresistance as the driving mechanism. The magnetic
      field induced change in resistivity in Ni81Fe19/Au multilayers directly affects
      the diagonal elements of the dielectric tensor of the system, mainly in the mid
      IR range, via the magnetorefractive effect. With magnetic fields as small as 50
      Oe, we postulate the possibility to modulate the response of such continuous and
      patterned structures in a contactless, easy to implement fashion. The potential
      application impact of this modulation concept is analyzed.

PMID- 29041073
TI  - Improved wavefront correction for coherent image restoration.
AB  - Coherent imaging has a wide range of applications in, for example, microscopy,
      astronomy, and radar imaging. Particularly interesting is the field of
      microscopy, where the optical quality of the lens is the main limiting factor. In
      this article, novel algorithms for the restoration of blurred images in a system
      with known optical aberrations are presented. Physically motivated by the scalar
      diffraction theory, the new algorithms are based on Haugazeau POCS and FISTA, and
      are faster and more robust than methods presented earlier. With the new approach
      the level of restoration quality on real images is very high, thereby blurring
      and ringing caused by defocus can be effectively removed. In classical
      microscopy, lenses with very low aberration must be used, which puts a practical
      limit on their size and numerical aperture. A coherent microscope using the novel
      restoration method overcomes this limitation. In contrast to incoherent
      microscopy, severe optical aberrations including defocus can be removed, hence
      the requirements on the quality of the optics are lower. This can be exploited
      for an essential price reduction of the optical system. It can be also used to
      achieve higher resolution than in classical microscopy, using lenses with high
      numerical aperture and high aberration. All this makes the coherent microscopy
      superior to the traditional incoherent in suited applications.

PMID- 29041074
TI  - Low-loss and reflection-free fused type fan-out device for 7-core fiber based on
      a bundled structure.
AB  - We describe a fused type fan-out device for 7-core fiber based on a bundled
      structure, which has no taper structure and a highly accurate core arrangement.
      We evaluated the repeatability of the splice loss characteristics of the fan-out
      device by splice testing 10 samples, resulting in an average splice loss of as
      low as 0.3 dB with a deviation of 0.048 dB. The crosstalk between the center and
      outer cores was less than -52 dB. Furthermore, the power damage threshold was
      higher than 1 W and the amount of Fresnel reflection at the splice point between
      the fiber bundle and the 7-core fiber was lower than the Rayleigh scattering
      level because of the arc fusion splicing.

PMID- 29041075
TI  - Understanding the effects of groove structures on the MTF.
AB  - We develop a theory for understanding and modeling the effects of mid-spatial
      frequency (MSF) structures on the modulation transfer function (MTF) of an
      imaging system. We show that the MTF is related through Fourier transformation to
      what we call the pupil-difference probability density (PDPD) function. This
      relation is illustrated for several one-dimensional periodic groove patterns. We
      also consider two-dimensional pupils, particularly those presenting straight and
      circular concentric periodic surface errors, similar to those resulting from
      diamond turning and milling processes of freeform optical manufacturing, and
      develop simple approximations for the MTF based on the PDPD. Our approach
      provides an analytic way to understand the effects of tool profiles, as well as
      other freeform manufacturing parameters.

PMID- 29041076
TI  - Experimental measurement of supercontinuum coherence in highly nonlinear soft
      glass photonic crystal fibers.
AB  - We present experimental measurements illustrating the power-dependent coherence
      evolution for supercontinuum generated in highly nonlinear SF6 photonic crystal
      fibers. The measurements were performed for fiber lengths close to and much
      longer than the soliton fission length. Simulations of the spectral evolution
      were also carried out to accompany the experimental observation. Many parameters
      were estimated by matching the simulated and the measured evolution. Both the
      measured and the simulated coherence evolution confirm the association between
      coherence degradation and soliton fission.

PMID- 29041077
TI  - Extended C-band tunable multi-channel InP-based coherent receiver PICs.
AB  - Fully integrated monolithic, multi-channel InP-based coherent receiver PICs and
      transceiver modules with extended C-band tunability are described. These PICs
      operate at 33 and 44 Gbaud per channel under dual polarization (DP) 16-QAM
      modulation. Fourteen-channel monolithic InP receiver PICs show integration and
      data rate scaling capability to operate at 44 Gbaud under DP 16-QAM modulation
      for combined 4.9 Tb/s total capacity. Six channel simultaneous operation of a
      commercial transceiver module at 33 Gbaud is demonstrated for a variety of
      modulation formats including DP 16-QAM for >1.2Tbit/s aggregate data capacity.

PMID- 29041078
TI  - Fast ultra-wideband microwave spectral scanning utilizing photonic wavelength-
      and time-division multiplexing.
AB  - A high-speed ultra-wideband microwave spectral scanning system is proposed and
      experimentally demonstrated. Utilizing coherent dual electro-optical frequency
      combs and a recirculating optical frequency shifter, the proposed system realizes
      wavelength- and time-division multiplexing at the same time, offering flexibility
      between scan speed and size, weight and power requirements (SWaP). High-speed
      spectral scanning spanning from ~1 to 8 GHz with ~1.2 MHz spectral resolution is
      achieved experimentally within 14 us. The system can be easily scaled to higher
      bandwidth coverage, faster scanning speed or finer spectral resolution with
      suitable hardware.

PMID- 29041079
TI  - Optimization of instrument matrix for Mueller matrix ellipsometry based on
      partial elements analysis of the Mueller matrix.
AB  - We consider the Mueller matrix ellipsometry (MME) measuring the ellipsometric
      parameters of the isotropic sample and the anisotropic sample under certain
      conditions in the presence of either Gaussian additive noise or Poisson shot
      noise. In this case, the ellipsometric parameters only relate to partial elements
      in Mueller matrix, and we optimize the instrument matrices of polarization state
      generator (PSG) and analyzer (PSA) to minimize the total measurement variance for
      these elements, in order to decrease the variance of the estimator of
      ellipsometric parameters. Compared with the previous instrument matrices, the
      optimal instrument matrices in this paper can effectively decrease the
      measurement variance and thus statistically improve the measurement precision of
      the ellipsometric parameters. In addition, it is found that the optimal
      instrument matrices for Poisson shot noise are same to those for Gaussian
      additive noise, and furthermore, the optimal instrument matrices do not depend on
      the ellipsometric parameters to be measured, which means that the optimal
      instrument matrices of MME proposed in this paper can be widely applied in
      various cases.

PMID- 29041080
TI  - Strain sensor based on gourd-shaped single-mode-multimode-single-mode hybrid
      optical fibre structure.
AB  - A fibre-optic strain sensor based on a gourd-shaped joint multimode fibre (MMF)
      sandwiched between two single-mode fibres (SMFs) is described both theoretically
      and experimentally. The cladding layers of the two MMFs are reshaped to form a
      hemisphere using an electrical arc method and spliced together, yielding the
      required gourd shape. The gourd-shaped section forms a Fabry-Perot cavity between
      the ends of two adjacent but non-contacting multimode fibres' core. The
      effectiveness of the multimode interference based on the Fabry-Perot
      interferometer (FPI) formed within the multimode inter-fibre section is greatly
      improved resulting in an experimentally determined strain sensitivity of -2.60
      pm/MUepsilon over the range 0-1000 MUepsilon. The sensing characteristics for
      temperature and humidity of this optical fibre strain sensor are also
      investigated.

PMID- 29041081
TI  - 140 W peak power laser system tunable in the LWIR.
AB  - We present a high peak power rapidly tunable laser system in the long-wave
      infrared comprising an external-cavity quantum cascade laser (EC-QCL) broadly
      tunable from 8 to 10 um and an optical parametric amplifier (OPA) based on quasi
      phase-matching in orientation-patterned gallium arsenide (OP-GaAs) of fixed
      grating period. The nonlinear crystal is pumped by a pulsed fiber laser system to
      achieve efficient amplification in the OPA. Quasi phase-matching remains
      satisfied when the EC-QCL wavelength is swept from 8 to 10 um with a crystal of
      fixed grating period through tuning the pump laser source around 2 um. The OPA
      demonstrates parametric amplification from 8 um to 10 um and achieves output peak
      powers up to 140 W with spectral linewidths below 3.5 cm-1. The beam profile
      quality (M2) remains below 3.4 in both horizontal and vertical directions.
      Compared to the EC-QCL, the linewidth broadening is attributed to a coupling with
      the OPA.

PMID- 29041082
TI  - Optical directional amplification in a three-mode optomechanical system.
AB  - We study the directional amplification of an optical probe field in a three-mode
      optomechanical system, where the mechanical resonator interacts with two linearly
      coupled optical cavities and the cavities are driven by strong optical pump
      fields. The optical probe field is injected into one of the cavity modes, and at
      the same time, the mechanical resonator is subject to a mechanical drive with the
      driving frequency equal to the frequency difference between the optical probe and
      pump fields. We show that the transmission of the probe field can be amplified in
      one direction and de-amplified in the opposite direction. This directional
      amplification or de-amplification results from the constructive or destruction
      interference between different transmission paths in this three-mode
      optomechanical system.

PMID- 29041083
TI  - Optical sectioning in optical resolution photo acoustic microscopy.
AB  - We report a novel optical resolution photoacoustic microscopy concept to obtain
      an axial resolution only by optical methods. The photoacoustic signal is
      generated through a non-radiative relaxation from a level that is populated by
      excited state absorption. This two-step excitation process of a single laser
      enables to achieve an optical sectioning without any acoustic selectivity,
      whereby a full optical resolution photoacoustic microscopy is obtained. We bring
      a proof of this concept using Rhodamine and Zinc Tetraphenylporphyrin dyes known
      for their efficient excited state absorption process.

PMID- 29041084
TI  - Humidity-insensitive temperature sensor based on a quartz capillary anti-resonant
      reflection optical waveguide.
AB  - A compact, humidity-insensitive, fiber optic temperature sensor based on a quartz
      capillary, antiresonant reflecting optical waveguide was proposed and
      experimentally demonstrated. The transmission spectral responses of the proposed
      sensor were experimentally investigated regarding temperature variation and
      environmental humidity. Resonant dips exhibited temperature sensitivity as large
      as 201 pm/ degrees C from -30 to 45  degrees C in a humid environment. By coating
      a sufficiently thick gold film onto the sensor surface, the humidity cross
      sensitivity issue was effectively resolved. This proposed sensor was anticipated
      to find potential applications in humid environments, and moreover, immunity to
      humidity-sensitivity ensures its applicability in marine environments.

PMID- 29041085
TI  - Practical system for the generation of pulsed quantum frequency combs.
AB  - The on-chip generation of large and complex optical quantum states will enable
      low-cost and accessible advances for quantum technologies, such as secure
      communications and quantum computation. Integrated frequency combs are on-chip
      light sources with a broad spectrum of evenly-spaced frequency modes, commonly
      generated by four-wave mixing in optically-excited nonlinear micro-cavities,
      whose recent use for quantum state generation has provided a solution for
      scalable and multi-mode quantum light sources. Pulsed quantum frequency combs are
      of particular interest, since they allow the generation of single-frequency-mode
      photons, required for scaling state complexity towards, e.g., multi-photon
      states, and for quantum information applications. However, generation schemes for
      such pulsed combs have, to date, relied on micro-cavity excitation via lasers
      external to the sources, being neither versatile nor power-efficient, and
      impractical for scalable realizations of quantum technologies. Here, we introduce
      an actively-modulated, nested-cavity configuration that exploits the resonance
      pass-band characteristic of the micro-cavity to enable a mode-locked and energy
      efficient excitation. We demonstrate that the scheme allows the generation of
      high-purity photons at large coincidence-to-accidental ratios (CAR). Furthermore,
      by increasing the repetition rate of the excitation field via harmonic mode
      locking (i.e. driving the cavity modulation at harmonics of the fundamental
      repetition rate), we managed to increase the pair production rates (i.e. source
      efficiency), while maintaining a high CAR and photon purity. Our approach
      represents a significant step towards the realization of fully on-chip, stable,
      and versatile sources of pulsed quantum frequency combs, crucial for the
      development of accessible quantum technologies.

PMID- 29041086
TI  - Ultrabroadband 2D electronic spectroscopy with high-speed, shot-to-shot
      detection.
AB  - Two-dimensional electronic spectroscopy (2DES) is an incisive tool for
      disentangling excited state energies and dynamics in the condensed phase by
      directly mapping out the correlation between excitation and emission frequencies
      as a function of time. Despite its enhanced frequency resolution, the spectral
      window of detection is limited to the laser bandwidth, which has often hindered
      the visualization of full electronic energy relaxation pathways spread over the
      entire visible region. Here, we describe a high-sensitivity, ultrabroadband 2DES
      apparatus. We report a new combination of a simple and robust setup for increased
      spectral bandwidth and shot-to-shot detection. We utilize 8-fs supercontinuum
      pulses generated by gas filamentation spanning the entire visible region (450 -
      800 nm), which allows for a simultaneous interrogation of electronic transitions
      over a 200-nm bandwidth, and an all-reflective interferometric delay system with
      angled nanopositioner stages achieves interferometric precision in coherence time
      control without introducing wavelength-dependent dispersion to the ultrabroadband
      spectrum. To address deterioration of detection sensitivity due to the inherent
      instability of ultrabroadband sources, we introduce a 5-kHz shot-to-shot, dual
      chopping acquisition scheme by combining a high-speed line-scan camera and two
      optical choppers to remove scatter contributions from the signal. Comparison of
      2D spectra acquired by shot-to-shot detection and averaged detection shows a 15
      fold improvement in the signal-to-noise ratio. This is the first direct
      quantification of detection sensitivity on a filamentation-based ultrabroadband
      2DES apparatus.

PMID- 29041087
TI  - Thermalization of one-dimensional photon gas and thermal lasers in erbium-doped
      fibers.
AB  - We demonstrate thermalization and Bose-Einstein (BE) distribution of photons in
      standard erbium-doped fibers (edf) in a broad spectral range up to ~200nm at the
      1550nm wavelength regime. Our measurements were done at a room temperature ~300K
      and 77K. It is a special demonstration of thermalization of photons in fiber
      cavities and even in open fibers. They are one-dimensional (1D), meters-long,
      with low finesse, high loss and small capture fraction of the spontaneous
      emission. Moreover, we find in the edf cavities coexistence of thermal
      equilibrium (TE) and thermal lasing without an overall inversion (T-LWI). The
      experimental results are supported by a theoretical analysis based on the rate
      equations.

PMID- 29041088
TI  - Pulsed quantum continuous-variable optoelectromechanical transducer.
AB  - We propose a setup allowing to entangle two directly non-interacting radiation
      modes applying four sequential pulsed quantum resonant interactions with a noisy
      vibrational mode of a mechanical oscillator which plays the role of the mediator.
      We analyze Gaussian entanglement of the radiation modes generated by the
      transducer and confirm that the noisy mechanical mode can mediate generation of
      entanglement. The entanglement, however, is limited if the interaction gains are
      not individually optimized. We prove the robustness of the transducer to optical
      losses and the influence of the mechanical bath and propose the ways to achieve
      maximal performance through the individual optimization.

PMID- 29041089
TI  - LED power consumption in joint illumination and communication system.
AB  - This paper addresses the power penalty in an illumination LED caused by visible
      light communication (VLC). This study models the extra power consumption of the
      LED by taking into account the convex relation between the dissipated electrical
      power versus the LED current on one hand and the concave relation between the
      output luminous flux versus the current on the other hand. The ratio of the
      output luminous flux to input electrical power, which is known the LED luminous
      efficacy, is analyzed considering various recombination mechanisms and their
      dependency on current and temperature. As examples, the rapid light fluctuations
      induced by Pulse Amplitude Modulation (PAM) and orthogonal frequency division
      multiplexing (OFDM) are analyzed for joint illumination and communication (JIC)
      systems. Due to the signal modulation, there is a decrease in the output light of
      LED. Nevertheless, the total power offered to LED is larger than without
      modulation and thus extra heating occurs. Moreover, particularly when burst
      transmission is used in communication networks, visible flicker may occur.

PMID- 29041090
TI  - Toward near-white-light electroluminescence from n-ZnO nanocrystals/n-Si isotype
      heterojunctions via an AZO spectral scissor.
AB  - A strategy to realize ZnO-based near-white-light electroluminescence (EL) was
      proposed by utilizing and regulating the intrinsic defect-related emissions of
      solution-processed ZnO nanocrystals (NCs). Prototype near-white light-emitting
      diodes (LEDs) based upon this strategy were demonstrated by using n-ZnO NCs/n-Si
      isotype heterojunctions. The emission color of the n-ZnO NCs/n-Si isotype
      heterojunction LEDs was tuned toward near white by using an Al-doped ZnO (AZO)
      spectral "scissor" which can tailor the green light more severely, rather than
      the blue or red light. Moreover, quantum size effect was clearly observed in both
      the photoluminescence (PL) and EL spectra via the redshift of the near-band-edge
      UV emission of the ZnO NCs. The strategy using AZO spectral "scissors" to
      regulate the VO-related green emission of ZnO may present a promising pathway to
      realize ZnO-based white-light LEDs.

PMID- 29041091
TI  - Mathematical synthesis and analysis of a second-order magneto-electrically
      nonlinear metasurface.
AB  - We propose a discussion on the synthesis and scattering analysis of nonlinear
      metasurfaces. For simplicity, we investigate the case of a second-order nonlinear
      isotropic metasurface possessing both electric and magnetic linear and nonlinear
      susceptibility components. We next find the synthesis expressions relating the
      susceptibilities to the specified fields, which leads to the definition of the
      nonlinear metasurface conditions for no reflection, themselves revealing the
      nonreciprocal nature of such structures. Finally, we provide the approximate
      expressions of the scattered fields based on perturbation theory and compare the
      corresponding results to finite-difference time-domain simulations.

PMID- 29041092
TI  - Compact and broadband antenna based on a step-shaped metasurface.
AB  - A metasurface (MS) is highly useful for improving the performance of patch
      antennae and reducing their size due to their inherent and unique electromagnetic
      properties. In this paper, a compact and broadband antenna based on a step-shaped
      metasurface (SMS) at an operating frequency of 4.3 GHz is presented, which is fed
      by a planar monopole and enabled by selecting an SMS with high selectivity. The
      SMS consists of an array of metallic step-shaped unit cells underneath the
      monopole, which provide footprint miniaturization and bandwidth expansion.
      Numerical results show that the SMS-based antenna with a maximum size of
      0.42lambda02 (where lambda0 is the operating wavelength in free space) exhibits a
      22.3% impedance bandwidth (S11 < -10 dB) and a high gain of more than 7.15 dBi
      within the passband. Experimental results at microwave frequencies verify the
      performance of the proposed antenna, demonstrating substantial consistency with
      the simulation results. The compact and broadband antenna therefore predicts
      numerous potential applications within modern wireless communication systems.

PMID- 29041093
TI  - Efficient 5.2 um wavelength fiber-to-chip grating couplers for the Ge-on-Si and
      Ge-on-SOI mid-infrared waveguide platform.
AB  - We present the design, fabrication and characterization of efficient fiber-to
      chip grating couplers on a Germanium-on-Silicon (Ge-on-Si) and Germanium-on
      silicon-on-insulator (Ge-on-SOI) platform in the 5 um wavelength range. The best
      grating couplers on Ge-on-Si and Ge-on-SOI have simulated coupling efficiencies
      of -4 dB (40%) with a 3 dB bandwidth of 180 nm and -1.5 dB (70%) with a 3 dB
      bandwidth of 200 nm, respectively. Experimentally, we show a maximum efficiency
      of -5 dB (32%) and a 3 dB bandwidth of 100 nm for Ge-on-Si grating couplers, and
      a -4 dB (40%) efficiency with a 3 dB bandwidth of 180 nm for Ge-on-SOI couplers.

PMID- 29041094
TI  - Photonic generation of RF binary digitally modulated signals.
AB  - A novel scheme of microwave photonic generation of binary digitally modulated
      signals is proposed and experimentally demonstrated, which can simultaneously
      generate 2ASK, 2PSK and 2FSK. By dynamically manipulating an optical frequency
      comb, different modulation formats can be switched. Moreover, the bit rate and
      carrier frequency of the generated RF signals can be tuned.

PMID- 29041095
TI  - Focused, evanescent, hollow, and collimated beams formed by microaxicons with
      different conical angles.
AB  - Diffraction patterns formed by axicons with different tip (vertex) angles are
      analytically and numerically investigated. Results show that the axicon (or
      tapered dielectric probe) can form an extended axial light beam, a compact
      evanescent field, a hollow beam, and a collimated beam, depending on the vertex
      angle. Two-dimensional and three-dimensional models of a tapered dielectric probe
      show that, with small changes to the vertex angle, light transmitted by the probe
      is scattered rather than focused, and vice versa. Angle meanings corresponded to
      boundary transitions have a quantum character and densify as the angle approaches
      zero. These features should be taken into consideration when manufacturing
      microaxicons intended for various applications.

PMID- 29041096
TI  - Temperature dependent photoluminescence of composition tunable ZnxAgInSe quantum
      dots and temperature sensor application.
AB  - Quantum dots (QDs) exhibit not only wide tunability of luminescence but also
      complex optical properties because of the large degree of freedom in their
      structure and chemical composition. Quaternary ZnxAgInSe QDs with different Zn/Ag
      ratios were synthesized and examined as temperature sensors. The relationship
      among the luminescence energy, emission intensity, and full-width at half-maximum
      (FWHM) of the emission band at different temperatures was investigated. To
      understand the photoluminescence mechanism, time-resolved photoluminescence
      spectra were recorded. Moreover, the dependence of the luminescence peak energy
      and FWHM on temperature was investigated, and a small deviation from the actual
      temperature was observed, indicative of the use of ZnxAgInSe QDs as high
      sensitivity temperature sensors.

PMID- 29041097
TI  - Enhancing the signal-to-noise ratio of FTIR spectrometers by a digital J-Stop.
AB  - Fourier transform infrared (FTIR) spectrometers have been widely used as very
      important analytical tools in various fields. Owing to the Jacquinot Stop (J
      Stop), high throughput is a widely recognized advantage inherent to Fourier
      transform interferometers. However, there is a fundamental trade-off between the
      throughput and spectral resolution, which is primarily affected by the size of
      the J-Stop. So far, no effective optimization methods have been provided to break
      the trade-off. In this paper, we introduce a numeric technique of the digital J
      Stop, which has been experimentally validated using the FTIR spectra collected
      from a commercial spectrometer. The result shows that the throughput can be
      increased by ~12 times, while the spectral resolution is also improved. In this
      way, the signal-to-noise ratio (SNR) gets improved by ~3 times.

PMID- 29041098
TI  - Design and characterization of a p+/n-well SPAD array in 150nm CMOS process:
      erratum.
AB  - An erratum is presented to correct a reference mistake in Table 1 in Sect. 4 of
      [Opt. Express25, 12765 (2017)].

PMID- 29041099
TI  - Nanostructured antireflective in-plane solar harvester.
AB  - In this work, we demonstrate a two-dimensional nano-hole array that can reduce
      reflection losses while passively trapping and harvesting incident light. The
      surface structure is designed to scavenge a small portion of incident light that
      would typically be lost due to Fresnel reflection, while the majority of light
      transmits unobstructed like a regular window. The trapping mechanism is dependent
      on angle and wavelength, and can be designed to selectively trap narrow
      wavelength bands using the constructed theoretical models. We demonstrate that
      structures with periods of 275 nm and 325 nm can trap different wavelength range
      within the visible spectrum, while simultaneously suppressing reflection losses.
      The trapping effect can be observed visually, and can be converted to a current
      output using a photovoltaic (PV) cell on the glass edge. The fabrication of such
      materials employs a simple replication process, and can be readily scaled up for
      large-scale manufacturing. The demonstrated solar harvester can be potentially be
      widely deployed in residential and commercial buildings as multifunctional
      windows for solar energy harvesting, scavenging, spectra splitting, and anti
      glare properties.

PMID- 29041100
TI  - Estimation of coniferous forest aboveground biomass with aggregated airborne
      small-footprint LiDAR full-waveforms.
AB  - Forest aboveground biomass (AGB) is critical for assessing forest productivity
      and evaluating carbon sequestration rates. Discrete-return LiDAR has been widely
      used to estimate forest AGB, however, fewer studies have estimated the coniferous
      forest AGB using airborne small-footprint full-waveform LiDAR data. The objective
      of this study was to extract a suite of newly proposed metrics from airborne
      small-footprint full-waveform LiDAR data and to evaluate the ability of these
      metrics in estimating coniferous forest AGB. To achieve this goal, each waveform
      was first preprocessed, including de-noising, smoothing, and normalization. Next,
      all the waveforms within each plot were aggregated into a large pseudo waveform
      and the return energy profile was generated. Then, the foliage profile was
      retrieved from the return energy profile based on the Geometric Optical and
      Radiative Transfer (GORT) model. Finally, a series of new return energy profile
      metrics and foliage profile metrics were extracted to estimate forest AGB. Simple
      linear regression was conducted to assess the correlation between each LiDAR
      metric and forest AGB. Stepwise multiple regression analysis was then carried out
      to select important prediction metrics and establish the optimal forest AGB
      estimation model. Results indicated that both return energy profile and foliage
      profile based height-related metrics were strongly correlated to forest AGB. The
      energy weighted canopy height (HEweight) (R = 0.88) and foliage area weighted
      height (HFweight) (R = 0.89) all had the highest correlation coefficients with
      forest AGB in return energy profile metrics and foliage profile metrics
      respectively. Energy height percentiles and foliage height percentiles also had
      the ability to explain AGB variation. The energy-related metrics, foliage area
      related metrics, and bounding volume-related metrics derived from the return
      energy profile and foliage profile were not all sensitive to forest AGB. This
      study also concluded that combining return energy profile metrics and foliage
      profile metrics could improve the accuracy of forest AGB estimation, and the
      optimal model contained the metrics of HFweight, HEweight, and VolumemaxHE, which
      is the product of the maximum canopy return energy profile amplitude (maxCE) and
      the maximum height of return energy profile (maxHE).

PMID- 29041101
TI  - Thin-film camera using luminescent concentrators and an optical Soller
      collimator: publisher's note.
AB  - This publisher's note amends the author list of [Opt. Express25, 18526 (2017)].

PMID- 29041102
TI  - Analysis for the phase-diffusion effect in a phase-shifted helical long-period
      fiber grating and its pre-compensation.
AB  - Through analyzing the structure of the phase-shifted helical long-period fiber
      grating (HLPG), which is fabricated based on the thermally twisting method, we
      have shown that there exists a phase-diffusion effect when the thermal region is
      larger than the grating period itself, i.e., the inserted phase preset at
      particular period will be diffused to several neighboring periods, which causes a
      large distortion in the transmission spectrum. We have analytically proved that
      this kind of phase-diffusion effect can be quantified by doing the convolution
      between the preset phase function and the phase-diffusion function in spatial
      domain. According to the analytical results, we have proposed and successfully
      demonstrated a pre-compensation method to solve the phase diffusion effect. As an
      example, a phase-shifted HLPG with pi phase-shift precisely inserted at middle
      position of the grating has been presented.

PMID- 29041103
TI  - Ultraslow weak-light solitons and their storage and retrieval in a kagome
      structured hollow-core photonic crystal fiber.
AB  - We investigate the formation and propagation of ultraslow weak-light solitons and
      their memory in the atomic gas filled in a kagome-structured hollow-core photonic
      crystal fiber (HC-PCF) via electromagnetically induced transparency (EIT). We
      show that, due to the strong light-atom coupling contributed by the transverse
      confinement of the HC-PCF, the EIT and hence the optical Kerr nonlinearity of the
      system can be largely enhanced, and hence optical solitons with very short
      formation distance, ultraslow propagation velocity, and extremely low generation
      power can be realized. We also show that the optical solitons obtained can not
      only be robust during propagation, but also be stored and retrieved with high
      efficiency through the switching off and on of a control laser field. The results
      reported herein are promising for practical applications of all-optical
      information processing and transmission via the ultraslow weak-light solitons and
      the kagome-structured HC-PCF.

PMID- 29041104
TI  - Modeling of ultrashort pulse amplification with gain saturation.
AB  - A new method for the realistic modeling of ultrashort pulse amplification under
      conditions of strong gain saturation has been developed. Both the frequency
      dependence and the time dependence of the gain are properly taken into account.
      The method can, for example, be applied to chirped-pulse bulk and fiber
      amplifiers, but is not restricted to pulses with particular spectral or temporal
      properties.

PMID- 29041105
TI  - Spin Hall effect of reflected light in dielectric magneto-optical thin film with
      a double-negative metamaterial substrate.
AB  - We study spin the Hall effect (SHE) of reflected light in a dielectric magneto
      optical thin film of Ce1Y2Fe5O12 (Ce:YIG) with a double-negative (DNG)
      metamaterial substrate. The spin-dependent splitting expressions of left- and the
      right-handed circularly polarized (LHCP and RHCP) components in longitudinal,
      polar and transverse magneto-optical Kerr effect (MOKE) configurations are
      obtained. Meanwhile we first obtain the analytical expressions of the SHE shift
      of reflected light for three MOKE configurations by proper approximation. Owing
      to the enhancement of the MOKE by DNG metamaterial, the external magnetic field
      shows a large enhancement and modulation to spin-dependent splitting of reflected
      light. Based on simulation results, the influences of magnetic field direction
      and substrate material on the transverse centroid shifts of the reflected left-
      and right-handed circularly polarized light perpendicular to incident plane are
      analyzed. We find the maximum spin-dependent splitting between LHCP and RHCP
      components achieves about 9.2 MUm and the maximum value of the magneto-optical
      spin Hall effect (MOSHE) shift reaches 9 MUm in polar MOKE configuration. In
      order to make our results convincing we use a realizable DNG metamaterial with
      silver nanostructures as substrate to verify our conclusion. The DNG metamaterial
      provides a flexible method to manipulate and enhance SHE of light.

PMID- 29041106
TI  - Design of a broadband reciprocal optical diode in a silicon waveguide assisted by
      silver surface plasmonic splitter.
AB  - In this paper, we propose a new scheme for a reciprocal optical diode integrated
      in a multimode silicon waveguide. The compact 4MUm long functional region
      consists of a tapered coupler, a narrow single-mode waveguide, and a half
      elliptical silver surface plasmonic splitter with refractive index modification
      of silicon. This spatial asymmetric design achieves even-to-odd mode conversion
      in the forward direction and blocks propagation of the even mode in the backward
      direction. The maximum contrast ratio and forward transmission efficiency reach
      approximately 0.99 and 87% while the values respectively keep higher than 0.96
      and 80% within a 100nm operational bandwidth in a two-dimensional design. Both
      freestanding and SOI-based three-dimensional devices are simulated and at least a
      0.94 contrast ratio is observed. Moreover, the robustness is demonstrated by
      introducing deviations to the surface plasmonic splitter. The proposed scheme
      brings together advantages including a high contrast ratio (>0.94), a large
      operational bandwidth (100nm) and a small footprint (4MUm long).

PMID- 29041107
TI  - Self-equalizing photodiodes, a hybrid electro-optical approach to tackle
      bandwidth limitation in high-speed signaling.
AB  - In this paper we provide the design details of self-equalizing photodetectors
      which enable higher data rate transmission by improving the overall bandwidth of
      the bandwidth limited transmission link, through a hybrid electro-optical
      solution. Two different self-equalizing photodiodes, one having fixed
      equalization and the other being programmable are presented as proof of concept.

PMID- 29041108
TI  - Unraveling beam self-healing.
AB  - We show that, contrary to popular belief, diffraction-free beams may not only
      reconstruct themselves after hitting an opaque obstacle but also, for example,
      Gaussian beams. We unravel the mathematics and the physics underlying the self
      reconstruction mechanism and we provide for a novel definition for the minimum
      reconstruction distance beyond geometric optics, which is in principle applicable
      to any optical beam that admits an angular spectrum representation. Moreover, we
      propose to quantify the self-reconstruction ability of a beam via a newly
      established degree of self-healing. This is defined via a comparison between the
      amplitudes, as opposite to intensities, of the original beam and the obstructed
      one. Such comparison is experimentally accomplished by tailoring an innovative
      experimental technique based upon Shack-Hartmann wave front reconstruction. We
      believe that these results can open new avenues in this field.

PMID- 29041109
TI  - Sub-pixel projector calibration method for fringe projection profilometry.
AB  - Digital projectors are used as standard parts at present in fringe projection
      profilometry systems to project structured-light patterns onto the object surface
      to be measured, and the distortion of the projector lens must be calibrated and
      compensated accurately to satisfy the accuracy requirement of industrial
      applications. A novel method is proposed to determine the projector pixel
      coordinates of the marker points of a calibration target accurately in terms of
      projective transform. With the method, the projector can be calibrated with
      accuracy of sub-pixel level. The method is applicable for the calibration target
      with a chessboard pattern or a circle pattern, and the calibration result is
      independent on the results of camera calibration. Experimental results are shown
      to demonstrate the effectiveness and validity of the proposed method.

PMID- 29041110
TI  - 34 nm-wavelength-tunable picosecond Ho3+/Pr3+-codoped ZBLAN fiber laser.
AB  - We propose and demonstrate a broadly wavelength-tunable mode-locked Ho3+/Pr3+
      codoped ZBLAN fiber laser operating in the 3 MUm mid-infrared spectral region
      based on a semiconductor saturable absorber mirror. Wavelength selection is
      realized by rotating a plane ruled grating. The fiber laser exhibits stable
      continuous-wave mode-locking operation over a wide wavelength tuning range of 34
      nm (2842.2 nm~2876.2 nm), with a 10.17 MHz repetition rate and 22 ps pulse
      duration. Stable mode-locked pulses can be maintained until the launched pump
      power of 1.25 W. Maximum average output power of 127.7 mW and the corresponding
      pulse energy of 12.56 nJ are achieved. To the best of our knowledge, this is the
      first demonstration of a wavelength-tunable mode-locked fiber laser operating in
      the 3 MUm spectral region. Such simple, robust, and versatile mid-infrared
      picosecond laser source can find various applications in laser surgery,
      spectroscopy, and nonlinear frequency conversion.

PMID- 29041111
TI  - InGaN uLEDs integrated onto colloidal quantum dot functionalized ultra-thin
      glass.
AB  - Red-, orange-, and green-emitting integrated optoelectronic sources are
      demonstrated by transfer printing blue InGaN uLEDs onto ultra-thin glass
      platforms functionally enhanced with II-VI colloidal quantum dots (CQDs). The
      forward optical power conversion efficiency of these heterogeneously integrated
      devices is, respectively, 9%, 15%, and 14% for a blue light absorption over 95%.
      The sources are demonstrated in an orthogonal frequency division multiplexed
      (OFDM) visible light communication link reaching respective data transmission
      rates of 46 Mbps, 44 Mbps and 61 Mbps.

PMID- 29041112
TI  - Ultra-multiband absorption enhancement of graphene in a metal-dielectric-graphene
      sandwich structure covering terahertz to mid-infrared regime.
AB  - We investigate the absorption enhancement of an unstructured graphene sheet in a
      broad frequency range from terahertz (THz) to mid-infrared regime. Ultra
      multiband graphene absorption enhancement is observed by integrating graphene in
      a metal-dielectric-graphene (MDG) sandwich structure for polarized waves.
      Multiple order Fabry-Perot (FP) resonances are demonstrated to be responsible for
      the multiband absorption. Furthermore, perfect absorption is realized by
      introducing the MDG structure on a metal reflector to suppress the transmission
      channel. In addition, the absorption peaks can be easily tuned by changing the
      doping level of graphene. This work may have potential for improving the
      performance of graphene based optoelectrical devices and can be regarded as a
      demonstration of a tunable broadband near-perfect metamaterial absorber.

PMID- 29041113
TI  - Acceleration of sub-relativistic electrons with an evanescent optical wave at a
      planar interface.
AB  - We report on a theoretical and experimental study of the energy transfer between
      an optical evanescent wave, propagating in vacuum along the planar boundary of a
      dielectric material, and a beam of sub-relativistic electrons. The evanescent
      wave is excited via total internal reflection in the dielectric by an infrared
      (lambda = 2 MUm) femtosecond laser pulse. By matching the electron propagation
      velocity to the phase velocity of the evanescent wave, energy modulation of the
      electron beam is achieved. A maximum energy gain of 800 eV is observed,
      corresponding to the absorption of more than 1000 photons by one electron. The
      maximum observed acceleration gradient is 19 +/- 2 MeV/m. The striking advantage
      of this scheme is that a structuring of the acceleration element's surface is not
      required, enabling the use of materials with high laser damage thresholds that
      are difficult to nano-structure, such as SiC, Al2O3 or CaF2.

PMID- 29041114
TI  - Sinusoidal frequency scan OFDR with fast processing algorithm for distributed
      acoustic sensing.
AB  - Recently it was shown that sinusoidal frequency scan optical frequency domain
      reflectometry (SFS-OFDR) can achieve remarkable performance in applications of
      distributed acoustic sensing (DAS). The main advantage of SFS-OFDR is the
      simplicity with which highly accurate sinusoidal frequency scans can be generated
      (in comparison with linear frequency scans). One drawback of SFS-OFDR has been
      the computationally intensive algorithm it required for processing of the
      measured backscatter data. The complexity of this algorithm was O(N2) where N is
      the number of backscatter samples. In this work a fast processing algorithm for
      SFS-OFDR, with computational complexity O (N log N), is derived and its
      performance and limitations are studied in details. The new algorithm facilitated
      highly sensitive DAS operation over a sensing fiber of 64km, with 6.5m resolution
      and scan rate of 400Hz. The high sensitivity of the system was demonstrated in a
      field trial where it successfully detected human footsteps near the end of the
      fiber with excellent SNR.

PMID- 29041115
TI  - 53-dB phase noise suppression and Hz-range linewidth emission in compact
      Brillouin/erbium fiber laser.
AB  - We demonstrate 53-dB phase noise reduction in a compact Brillouin/erbium fiber
      laser (BEFL), which uses 4-m erbium-doped-fiber (EDF) providing both the
      Brillouin gain and linear gain. A 360-kHz-linewidth laser diode is used as the
      Brillouin pump (BP) and excites the Brillouin Stokes light. The linewidth of the
      BEFL is estimated 1.8-Hz based on the correlation between the linewidth and phase
      noise. Experimental result demonstrates 6-Hz linewidth by beating the emission of
      two compact BEFLs. This fiber laser provides a simple and effective method to
      reduce laser phase noise and realize ultra-narrow-linewidth light. It presents
      many applications in such as interferometric fiber sensing, coherent optical
      communications, optical clocks, and precise spectroscopy.

PMID- 29041116
TI  - Dissipation-assisted spin squeezing of nitrogen-vacancy centers coupled to a
      rectangular hollow metallic waveguide.
AB  - Spin squeezing has received much attention due to the interesting physics and
      important applications such as quantum metrology and quantum information
      processing. We here present a scheme to engineer stable spin squeezing in an
      array of nitrogen vacancy centers (NVCs) coupled to a rectangular hollow metallic
      waveguide. The remarkable feature of the waveguide as the common environment
      media is that one can switch on/off either the waveguide induced dipole-dipole
      interactions or correlated spontaneous emissions among the NVCs by designing
      their spatial separation. It permits us to achieve a dissipative Dicke model
      after the dipole-dipole interactions vanish due to destructive interference. With
      the external driving lasers on each NVC, a second-order phase transition is
      triggered, separating the steady state into two phases with and without
      collective spin squeezing. Supplying a physical realization of the dissipative
      Dicke model, our study gives a bridge between the generation of the stable spin
      squeezing and the phase transition physics.

PMID- 29041117
TI  - MoVIT: a tomographic reconstruction framework for 4D-CT.
AB  - 4D computed tomography (4D-CT) aims to visualise the temporal dynamics of a 3D
      sample with a sufficiently high temporal and spatial resolution. Successive time
      frames are typically obtained by sequential scanning, followed by independent
      reconstruction of each 3D dataset. Such an approach requires a large number of
      projections for each scan to obtain images with sufficient quality (in terms of
      artefacts and SNR). Hence, there is a clear trade-off between the rotation speed
      of the gantry (i.e. time resolution) and the quality of the reconstructed images.
      In this paper, the MotionVector-based Iterative Technique (MoVIT) is introduced
      which reconstructs a particular time frame by including the projections of
      neighbouring time frames as well. It is shown that such a strategy improves the
      trade-off between the rotation speed and the SNR. The framework is tested on both
      numerical simulations and on 4D X-ray CT datasets of polyurethane foam under
      compression. Results show that reconstructions obtained with MoVIT have a
      significantly higher SNR compared to the SNR of conventional 4D reconstructions.

PMID- 29041118
TI  - Broadband Fourier-transform spectrometer enabling modal subset identification in
      Fabry-Perot-based astrocombs.
AB  - A multi-GHz frequency comb (astrocomb) is typically realized by filtering modes
      of a sub-GHz frequency comb (source comb) in a Fabry-Perot etalon, which can lead
      to ambiguities in determining which subset of source comb modes has been
      filtered. Here we demonstrate a broadband Fourier-transform spectrometer (FTS)
      with a resolving power of R = 430,000 at 550 nm, and apply it to the
      identification of comb subsets from a filtered 1-GHz supercontinuum. After
      apodization the FTS demonstrated an instrument line shape width of 1.26 GHz which
      enabled individual comb-line positions to be identified with an uncertainty of
      17.6 MHz, a relative precision of 5 * 10-8. Correcting for air dispersion allowed
      the instrument to determine the comb-mode spacing to an accuracy of 300 Hz and
      filtered subsets of source comb modes to be uniquely distingished across the
      entire comb bandwidth from 550 to 900 nm. The inherently broadband design of the
      FTS makes it suitable in future applications for calibrating ultra-broadband
      astrocombs employed by instruments such as ELT HIRES.

PMID- 29041119
TI  - Towards 3D-photonic, multi-telescope beam combiners for mid-infrared
      astrointerferometry.
AB  - In the past two decades high precision optical astronomical interferometry has
      benefited from the use of photonic technologies. Today, near-infrared
      interferometric instruments deliver high-resolution, hyperspectral images of
      astronomical objects and combine up to 4 independent telescopes at a time thanks
      to integrated optics (IO). Following the success of IO interferometry, several
      initiatives aim at developing components which could combine simultaneously more
      telescopes and extend their operation beyond the near-infrared bands. Here we
      report on the development of multi-telescope IO beam combiners for mid-infrared
      interferometry exploiting the three-dimensional (3D) structuring capabilities of
      ultrafast laser inscription. We characterise the capability of a 2-telescope and
      a 4-telescope beam combiner to retrieve the visibility amplitude and phase of
      monochromatic light fields at a wavelength of 3.39 um. The combiner prototypes
      exploit different 3D architectures and are written with a femtosecond laser on
      substrates of Gallium Lanthanum Sulfide. Supporting numerical simulations of the
      performance of the beam combiners show that there is still room for improvement
      and indicate a roadmap for the development of future prototypes.

PMID- 29041120
TI  - Low-loss buried AlGaAs/AlOx waveguides using a quasi-planar process.
AB  - In this paper, we demonstrate that buried oxide-confined waveguides can be formed
      using a lateral oxidation process carried out through a discrete set of small
      diameter via-holes instead of the conventional scheme where the oxidation starts
      from the edges of etched mesas. The via-hole oxidation is shown to lead to
      straight waveguides with smooth oxide/semiconductor interfaces and whose
      propagation losses are similar to one obtained using the standard process but
      with the advantage of maintaining a quasi-planar wafer surface. It thereby paves
      the way towards a simplification of the fabrication of III-V-semiconductor-oxide
      photonic devices.

PMID- 29041121
TI  - Coherent beam combining and noise analysis of a colliding pulse modelocked
      VECSEL.
AB  - Optically-pumped SESAM-modelocked semiconductor disk lasers have become
      interesting ultrafast lasers with gigahertz pulse repetition rates, high average
      power and adjustable lasing wavelength. It is well established that colliding
      pulse modelocking (CPM) can generate both shorter pulses and improved stability.
      These improvements however typically come at the expense of a more complex ring
      cavity and two output beams. So far similar modelocking results have been
      obtained with CPM vertical external-cavity surface-emitting lasers (VECSELs) and
      with SESAM-modelocked VECSELs or modelocked integrated external-cavity surface
      emitting lasers (MIXSELs) in a linear cavity. However coherent beam combining of
      the two output beams of a CPM VECSEL could result in a significantly higher peak
      power. This is interesting for example for applications in biomedical microscopy
      and frequency metrology. Here we demonstrate with a more detailed noise analysis
      that for both output beams of a CPM VECSEL the pulse repetition rates and the
      carrier envelope offset frequencies are locked to each other. In contrast to
      standard SESAM-modelocked VECSELs in a linear cavity, we only have been able to
      actively stabilize the pulse repetition rate of the CPM VECSEL by cavity length
      control and not by pump-power control. Furthermore, a first coherent beam
      combining experiment of the two output beams is demonstrated.

PMID- 29041122
TI  - Open architecture time of flight 3D SWIR camera operating at 150 MHz modulation
      frequency.
AB  - In the past two decades 3-D cameras have proven to be one of the next revolutions
      in machine vision. However, these devices are still an emerging technology with a
      particularly narrow set of commercially available devices. In this paper, the
      concept and execution of the first short wavelength infrared (SWIR) time-of
      flight (ToF) 3-D camera system operating at a wavelength of 1550 nm is presented.
      By decoupling the optical and electrical components of the system in an open
      architecture we not only surpass many of the limitations of an on-chip integrated
      solution, but also can easily change the imaging device based on the requirements
      of the application. We achieve modulation frequencies up to 150 MHz, which
      exceeds the conventional values currently published for other large format
      modulators by about five times. This increase in the modulation frequency allows
      for a TOF camera with significantly higher depth resolution, while the open
      architecture design allows for a highly reconfigurable device that can be
      modified for specific working conditions.

PMID- 29041123
TI  - Nanoscale liquid crystal polymer Bragg polarization gratings.
AB  - We experimentally demonstrate nearly ideal liquid crystal (LC) polymer Bragg
      polarization gratings (PGs) operating at a visible wavelength of 450 nm and with
      a sub-wavelength period of 335 nm. Bragg PGs employ the geometric (Pancharatnam
      Berry) phase, and have many properties fundamentally different than their
      isotropic analog. However, until now Bragg PGs with nanoscale periods (e.g., <
      800 nm) have not been realized. Using photo-alignment polymers and high
      birefringence LC materials, we employ multiple thin sublayers to overcome the
      critical thickness threshold, and use chiral dopants to induce a helical twist
      that effectively generates a slanted grating. These LC polymer Bragg PGs manifest
      85-99% first-order efficiency, 19-29 degrees  field-of-view, Q ~ 17, 200 nm
      spectral bandwidth, 84 degrees  deflection angle in air (in one case), and
      efficient waveguide-coupling (in another case). Compared to surface-relief and
      volume-holographic gratings, they show high efficiency with larger
      angular/spectral bandwidths and potentially simpler fabrication. These nanoscale
      Bragg PGs manifest a 6pi rad/MUm phase gradient, the largest reported for a
      geometric-phase hologram while maintaining a first-order efficiency near 100%.

PMID- 29041124
TI  - Wavefront improvement in an end-pumped high-power Nd:YAG zigzag slab laser.
AB  - Techniques for wavefront improvement in an end-pumped Nd:YAG zigzag slab laser
      amplifier were proposed and demonstrated experimentally. First, a study on the
      contact materials was conducted to improve the heat transfer between the slab and
      cooling blocks and to increase the cooling uniformity. Among many attempts, only
      the use of silicon oil showed an improvement in the wavefront. Thus, the
      appropriate silicone oil was applied to the amplifier as a contact material. In
      addition, the wavefront compensation method using a glass rod array was also
      applied to the amplifier. A very low wavefront distortion was obtained through
      the use of a silicone-oil contact and glass rod array. The variance of the
      optical path difference for the entire beam height was 3.87 MUm at a pump power
      of 10.6 kW, and that for the 80% section was 1.69 MUm. The output power from the
      oscillator was 3.88 kW, which means the maximum output extracted from the
      amplifier at a pump power of 10.6 kW.

PMID- 29041125
TI  - Efficient continuous-wave diode-pumped Er3+:Yb3+:LaMgB5O10 laser with sapphire
      cooling at 1.57 MUm.
AB  - Efficient 1.57 MUm continuous-wave laser was demonstrated in an X-cut, 2.0 mm
      thick Er3+:Yb3+:LaMgB5O10 crystal with sapphire cooling end-pumped by a 976 nm
      laser diode. In a plano-concave cavity, a laser with a maximum output power of
      0.61 W and a slope efficiency of 23% was realized at an absorbed pump power of
      4.0 W. A continuous-wave 1566 nm micro-laser with a maximum output power of 0.47
      W and a slope efficiency of 16% was also obtained. The lasers were totally linear
      polarization parallel to the crystalline Z axis. The results show that the
      Er3+:Yb3+:LaMgB5O10 crystal with high thermal conductivity may be a good gain
      medium for laser around 1.55 MUm.

PMID- 29041126
TI  - Generation of V-point polarization singularity lattices.
AB  - V-points normally do not occur in generic light fields as compared to C-points
      and L-lines. In structured optical fields, simultaneous existence of C-points, V
      points and L-lines can be engineered in lattice forms. But lattices consisting
      only of V-points have not been realized so far. In this paper we demonstrate
      creation of lattices of V-point polarization singularities with translational
      periodicity. These lattice structures are obtained by the interference of four
      (six) linearly polarized plane waves arranged in symmetric umbrella geometry. The
      state of polarization of each beam is controlled by an S-waveplate. Since in a
      periodic lattice of polarization singularities the net charge in a unit cell is
      zero, the lattices are populated with positive and negative index V-point
      singularities. All the first order degenerate states of V-point singularities can
      be realized in the same setup by selective excitation of the S-waveplate.

PMID- 29041127
TI  - Experimental comparison of direct detection Nyquist SSB transmission based on
      silicon dual-drive and IQ Mach-Zehnder modulators with electrical packaging.
AB  - We have designed and fabricated a silicon photonic in-phase-quadrature (IQ)
      modulator based on a nested dual-drive Mach-Zehnder structure incorporating
      electrical packaging. We have assessed its use for generating Nyquist-shaped
      single sideband (SSB) signals by operating it either as an IQ Mach-Zehnder
      modulator (IQ-MZM) or using just a single branch of the dual-drive Mach-Zehnder
      modulator (DD-MZM). The impact of electrical packaging on the modulator bandwidth
      is also analyzed. We demonstrate 40 Gb/s (10Gbaud) 16-ary quadrature amplitude
      modulation (16-QAM) Nyquist-shaped SSB transmission over 160 km standard single
      mode fiber (SSMF). Without using any chromatic dispersion compensation, the bit
      error rates (BERs) of 5.4 * 10-4 and 9.0 * 10-5 were measured for the DD-MZM and
      IQ-MZM, respectively, far below the 7% hard-decision forward error correction
      threshold. The performance difference between IQ-MZM and DD-MZM is most likely
      due to the non-ideal electrical packaging. Our work is the first experimental
      comparison between silicon IQ-MZM and silicon DD-MZM in generating SSB signals.
      We also demonstrate 50 Gb/s (12.5Gbaud) 16-QAM Nyquist-shaped SSB transmission
      over 320 km SSMF with a BER of 2.7 * 10-3. Both the silicon IQ-MZM and the DD-MZM
      show potential for optical transmission at metro scale and for data center
      interconnection.

PMID- 29041128
TI  - Explanation of low efficiency droop in semipolar (202-1-) InGaN/GaN LEDs through
      evaluation of carrier recombination coefficients.
AB  - We report the carrier dynamics and recombination coefficients in single-quantum
      well semipolar (202-1-) InGaN/GaN light-emitting diodes emitting at 440 nm with
      93% peak internal quantum efficiency. The differential carrier lifetime is
      analyzed for various injection current densities from 5 A/cm2 to 10 kA/cm2, and
      the corresponding carrier densities are obtained. The coupling of internal
      quantum efficiency and differential carrier lifetime vs injected carrier density
      (n) enables the separation of the radiative and nonradiative recombination
      lifetimes and the extraction of the Shockley-Read-Hall (SRH) nonradiative (A),
      radiative (B), and Auger (C) recombination coefficients and their n-dependency
      considering the saturation of the SRH recombination rate and phase-space filling.
      The results indicate a three to four-fold higher A and a nearly two-fold higher
      B0 for this semipolar orientation compared to that of c-plane reported using a
      similar approach [A. David and M. J. Grundmann, Appl. Phys. Lett. 96, 103504
      (2010)]. In addition, the carrier density in semipolar (202-1-) is found to be
      lower than the carrier density in c-plane for a given current density, which is
      important for suppressing efficiency droop. The semipolar LED also shows a two
      fold lower C0 compared to c-plane, which is consistent with the lower relative
      efficiency droop for the semipolar LED (57% vs. 69%). The lower carrier density,
      higher B0 coefficient, and lower C0 (Auger) coefficient are directly responsible
      for the high efficiency and low efficiency droop reported in semipolar (202-1-)
      LEDs.

PMID- 29041129
TI  - Particle-particle interactions in large, sparse arrays of randomly distributed
      plasmonic metal nanoparticles: a two-particle model.
AB  - A two-particle model is proposed which enables the assessment of particle
      particle interactions in large, sparse arrays of randomly distributed plasmonic
      metal nanoparticles of arbitrary geometry in inhomogeneous environments. The two
      particle model predicts experimentally observed peak splittings in the extinction
      cross section spectrum for randomly distributed gold nanocones on a TiO2:Er3+
      thin film with average center-to-center spacings of 3-5 diameters. The main
      physical mechanism responsible is found to be interference between the incident
      field and the far-field component of the single-particle scattered field which is
      guided along the film.

PMID- 29041130
TI  - Spectral efficient 64-QAM-OFDM terahertz communication link.
AB  - We report on a record spectral efficient terahertz communication system using a
      coherent radio-over-fiber (CRoF) approach. High spectral efficient back-to-back
      and wireless THz transmission around 325 GHz is experimentally demonstrated using
      a 64-QAM-OFDM modulation format and a 10 GHz wide wireless channel resulting in a
      data rate of 59 Gbit/s.

PMID- 29041131
TI  - Chirp management in silicon-graphene electro absorption modulators.
AB  - We study the frequency chirp properties of graphene-on-silicon electro-absorption
      modulators (EAMs). By experimentally measuring the chirp of a 100 um long single
      layer graphene EAM, we show that the optoelectronic properties of graphene induce
      a large positive linear chirp on the optical signal generated by the modulator,
      giving rise to a maximum shift of the instantaneous frequency up to 1.8 GHz. We
      exploit this peculiar feature for chromatic-dispersion compensation in fiber
      optic transmission thanks to the pulse temporal lensing effect. In particular, we
      show dispersion compensation in a 10Gb/s transmission experiment on standard
      single mode fiber with temporal focusing distance (0-dB optical-signal-to-noise
      ratio penalty) of 60 km, and also demonstrate 100 km transmission with a bit
      error rate largely lower than the conventional Reed-Solomon forward error
      correction threshold of 10-3.

PMID- 29041132
TI  - Wide bandwidth and flat multiwavelength Brillouin-erbium fiber laser.
AB  - A wide bandwidth and flat multiwavelength Brillouin-erbium fiber laser is
      demonstrated experimentally. In the proposed laser setup, the combination of a
      Brillouin mirror with feedback and a ring cavity with four-wave mixing assistance
      is realized. The efficiency of Brillouin Stokes lines generation is enhanced by
      the feedback-based Brillouin mirror structure. The effect of four-wave mixing in
      highly nonlinear fiber increases the generation of Brillouin Stokes lines in a
      wider bandwidth. The laser lines over 16 nm bandwidth (i.e 200 channels) within
      4.65 dB power difference are obtained. The generated laser lines span from 1534
      to 1550 nm with wavelength spacing of 0.08 nm and optical signal-to-noise ratio
      of at least 15 dB. The laser can also be freely tuned over 32 nm and is stable
      with power fluctuations of 0.7 dB over 1 hour duration.

PMID- 29041133
TI  - Nanopore thin film enabled optical platform for drug loading and release.
AB  - In this paper, a drug loading and release device fabricated using nanopore thin
      film and layer-by-layer (LbL) nanoassembly is reported. The nanopore thin film is
      a layer of anodic aluminum oxide (AAO), consisting of honeycomb-shape nanopores.
      Using the LbL nanoassembly process, the drug, using gentamicin sulfate (GS) as
      the model, can be loaded into the nanopores and the stacked layers on the
      nanopore thin film surface. The drug release from the device is achieved by
      immersing it into flowing DI water. Both the loading and release processes can be
      monitored optically. The effect of the nanopore size/volume on drug loading and
      release has also been evaluated. Further, the neuron cells have been cultured and
      can grow normally on the nanopore thin film, verifying its bio-compatibility. The
      successful fabrication of nanopore thin film device on silicon membrane render it
      as a potential implantable controlled drug release device.

PMID- 29041134
TI  - Depth-filtering in common-path digital holographic microscopy.
AB  - We demonstrate a method to select different layers in a sample using a low
      coherent gating approach combined with a stable common-path quantitative phase
      imaging microscopy setup. The depth-filtering technique allows us to suppress the
      negative effects generated by multiple interference patterns of overlaying
      optical interfaces in the sample. It maintains the compact and stable common-path
      setup, while enabling images with a high phase sensitivity and acquisition speed.
      We use a holographic microscope in reflective geometry with a non-tunable low
      coherence light source. First results of this technique are shown by imaging the
      hardware layer of a standard micro-controller through its thinned substrate.

PMID- 29041135
TI  - Improved performance of multi-view fringe projection 3D microscopy.
AB  - Fringe projection 3D microcopy (FP-3DM) plays an increasingly important role in
      micro manufacturing and measurement. In recent decades, research on FP-3DM has
      made considerable progress. Nevertheless, some disadvantages arising from the
      limited depth of field, local specular reflection and occlusion still exist and
      need to be further addressed. In this paper, a multi-view FP-3DM (MVFP-3DM) is
      presented. Four imaging branches with the Scheimpflug condition and one vertical
      projection branch are deployed to establish the system. The system is described
      with a general imaging model, which is independent of the system configuration.
      In system calibration, the edge of binary fringe is used to locate the benchmark,
      which takes advantage of the fact that the edge will keep its position whether it
      is in focus or out of focus. Furthermore, a group of experiments prove that our
      proposed MVFP-3DM system can extend measurable range in depth, improve precision
      in 3D reconstruction and reduce occlusion.

PMID- 29041136
TI  - Switching terahertz wave with grating-coupled Kretschmann configuration.
AB  - We present a terahertz wave switch utilizing Kretschmann configuration which
      consists of high-refractive-index prism-liquid crystal-periodically grooved metal
      grating. The switching mechanism of the terahertz switch is based on spoof
      surface plasmon polariton (SSPP) excitation in the attenuated total reflection
      regime by changing the liquid crystal refractive index. The results highlighted
      the fact that the feasibility to "tune" the attenuated total reflection terahertz
      wave intensity by using the external applied bias voltage. The extinction ratio
      of the terahertz switch reaches 31.48dB. The terahertz switch has good control
      ability and flexibility, and can be used in potential terahertz free space device
      systems.

PMID- 29041137
TI  - Monitoring of continuous-variable quantum key distribution system in real
      environment.
AB  - How to guarantee the practical security of continuous-variable quantum key
      distribution (CVQKD) system has been an important issue in the quantum
      cryptography applications. In contrast to the previous practical security
      strategies, which focus on the intercept-resend attack or the Gaussian attack, we
      investigate the practical security strategy based on a general attack, i.e., an
      arbitrated individual attack or collective attack on the system by Eve in this
      paper. The low bound of intensity disturbance of the local oscillator signal for
      eavesdropper successfully concealing herself is obtained, considering all noises
      can be used by Eve in the practical environment. Furthermore, we obtain an
      optimal monitoring condition for the practical CVQKD system so that legitimate
      communicators can monitor the general attack in real-time. As examples, practical
      security of two special systems, i.e., the Gaussian modulated coherent state
      CVQKD system and the middle-based CVQKD system, are investigated under the
      intercept-resend attacks.

PMID- 29041138
TI  - WINDOW: wideband demodulator for optical waveforms.
AB  - Optical communication systems, which operate at very high rates, are often
      limited by the sampling rate bottleneck. The optical wideband regime may exceed
      analog to digital converters (ADCs) front-end bandwidth. Multi-channel sampling
      approaches, such as interleaved ADCs, also known as multicoset sampling in some
      contexts, have been proposed to sample the wideband signal using several
      channels. Each channel samples below the Nyquist rate such that the overall
      sampling rate is preserved. However, this scheme suffers from two practical
      limitations that make its implementation difficult. First, the inherent anti
      aliasing filter of the samplers distorts the wideband signal. Second, it requires
      accurate time shifts on the order of the signal's Nyquist rate, which are
      challenging to maintain. In this work, we propose an alternative multi-channel
      sampling scheme, the wideband demodulator for optical waveforms (WINDOW), based
      on analog RF demodulation, where each channel aliases the spectrum using a
      periodic mixing function before integration and sampling. We show that
      intentionally using the inherent ADC filter to perform integration increases the
      signal to noise ratio (SNR). We demonstrate both theoretically and through
      numerical experiments that our system outperforms interleaved sampling in terms
      of signal recovery and symbol estimation in the presence of both thermal and
      quantization noise but is slightly less robust to timing jitter. The main
      contribution of this work is the application of RF demodulation concepts proposed
      in the context of sub-Nyquist sampling, e.g. random demodulator and modulated
      wideband converter, to optical communication signals in the Nyquist regime. We
      develop a sampling scheme that presents an alternative for optical links where
      thermal noise in the receiver is the bottleneck.

PMID- 29041139
TI  - Crack detection in riveted lap joints using fiber laser acoustic emission
      sensors.
AB  - Fiber laser ultrasonic sensors are demonstrated to be capable of measuring
      acoustic emission generated by cracks in aluminum panels. A single laser sensor
      is integrated into a riveted lap joint, which is subject to accelerated fatigue.
      Acoustic emission generated by crack formation in the panel in addition to other
      acoustic events due to fretting within the joint are clearly resolved by the
      laser sensor. Localization of an acoustic emission event is demonstrated with a
      multiplexed array of three laser sensors. This manuscript also calculates the
      fundamental limit to displacement resolution of the fiber laser sensor and
      presents measurements of the directional response to Lamb waves. The high
      measurement resolution and multiplexing capability of the fiber laser ultrasonic
      sensor makes it an ideal candidate for structural health monitoring applications.

PMID- 29041140
TI  - Dispersion control of silicon nanophotonic waveguides using sub-wavelength
      grating metamaterials in near- and mid-IR wavelengths.
AB  - Controlling the group velocity dispersion of silicon nanophotonic waveguides has
      been recognized as a key ingredient to enhance the development of various on-chip
      optical applications. However, the strong wavelength dependence of the dispersion
      in waveguides implemented on the high index contrast silicon-on-insulator (SOI)
      platform substantially hinders their wideband operation, which in turn, limits
      their deployment. In this work, we exploit the potential of non-resonant sub
      wavelength grating (SWG) nanostructures to perform a flexible and wideband
      control of dispersion in SOI waveguides. In particular, we demonstrated that the
      overall dispersion of the SWG-engineered metamaterial waveguides can be tailored
      across the transparency window of the SOI platform, keeping easy-to-handle single
      etch step manufacturing. The SWG silicon waveguides overcladded by silicon
      nitride exhibit significant reduction of wavelength dependence of dispersion, yet
      providing intriguing and customizable synthesis of various attractive dispersion
      profiles. These include large normal up to low anomalous operation regimes, both
      of which could make a great promise for plethora of emerging applications in
      silicon photonics.

PMID- 29041141
TI  - Ultra-compact tunable silicon nanobeam cavity with an energy-efficient graphene
      micro-heater.
AB  - We propose and experimentally demonstrate an ultra-compact silicon photonic
      crystal nanobeam (PCN) cavity with an energy-efficient graphene micro-heater.
      Owing to the PCN cavity with an ultra-small optical mode volume of 0.145 um3, the
      light-matter interaction is greatly enhanced and the thermo-optic (TO) tuning
      efficiency is increased. The TO tuning efficiency is measured to be as high as
      1.5 nm/mW, which can be further increased to 3.75 nm/mW based on numerical
      simulations with an optimized structure. The time constants with a rise time
      constant of taurise = 1.11 MUs and a fall time constant of taufall = 1.47 MUs are
      obtained in the experiment.

PMID- 29041142
TI  - Integrated waveguide PIN photodiodes exploiting lateral Si/Ge/Si heterojunction.
AB  - Germanium photodetectors are considered to be mature components in the silicon
      photonics device library. They are critical for applications in sensing,
      communications, or optical interconnects. In this work, we report on design,
      fabrication, and experimental demonstration of an integrated waveguide PIN
      photodiode architecture that calls upon lateral double Silicon/Germanium/Silicon
      (Si/Ge/Si) heterojunctions. This photodiode configuration takes advantage of the
      compatibility with contact process steps of silicon modulators, yielding reduced
      fabrication complexity for transmitters and offering high-performance optical
      characteristics, viable for high-speed and efficient operation near 1.55 MUm
      wavelengths. More specifically, we experimentally obtained at a reverse voltage
      of 1V a dark current lower than 10 nA, a responsivity higher than 1.1 A/W, and a
      3 dB opto-electrical cut-off frequency over 50 GHz. The combined benefits of
      decreased process complexity and high-performance device operation pave the way
      towards attractive integration strategies to deploy cost-effective photonic
      transceivers on silicon-on-insulator substrates.

PMID- 29041143
TI  - Photoacoustic signal enhancements from gold nano-colloidal suspensions excited by
      a pair of time-delayed femtosecond pulses.
AB  - Photoacoustic signal enhancements were observed with a pair of time-delayed
      femtosecond pulses upon excitation of gold nanosphere colloidal suspension. A
      systematic experimental investigation of photoacoustic intensity within the delay
      time, Deltat = 0 to 15 ns, was carried out. The results revealed a significant
      enhancement factor of ~2 when the pre-pulse energy is 20-30% of the total energy.
      Pre-pulse and main pulse energy ratios, Ep(1):Es(2), were varied to determine the
      optimal ratio that yields to maximum photoacoustic signal enhancement. This
      enhancement was ascribed to the initial stage of thermalization and bubble
      generation in the nanosecond time scale. Pre-pulse scattering intensity
      measurements and numerical finite-difference time-domain calculations were
      performed to reveal dynamics and light field enchancement, respectively.

PMID- 29041144
TI  - OLT-centralized sampling frequency offset compensation scheme for OFDM-PON.
AB  - We propose an optical line terminal (OLT)-centralized sampling frequency offset
      (SFO) compensation scheme for adaptively-modulated OFDM-PON systems. By using the
      proposed SFO scheme, the phase rotation and inter-symbol interference (ISI)
      caused by SFOs between OLT and multiple optical network units (ONUs) can be
      centrally compensated in the OLT, which reduces the complexity of ONUs. Firstly,
      the optimal fast Fourier transform (FFT) size is identified in the intensity
      modulated and direct-detection (IMDD) OFDM system in the presence of SFO. Then,
      the proposed SFO compensation scheme including phase rotation modulation (PRM)
      and length-adaptive OFDM frame has been experimentally demonstrated in the
      downlink transmission of an adaptively modulated optical OFDM with the optimal
      FFT size. The experimental results show that up to +/- 300 ppm SFO can be
      successfully compensated without introducing any receiver performance penalties.

PMID- 29041145
TI  - Tightly focused optical field with controllable photonic spin orientation.
AB  - The spin angular momentum of photons offers a robust, scalable and high-bandwidth
      toolbox for many promising applications based upon spin-controlled manipulations
      of light. In this work, we develop a method to achieve controllable photonic spin
      orientation within a diffraction limited optical focal spot produced by a high
      numerical aperture objective lens. The required pupil field is found analytically
      through reversing the radiation patterns from two electric dipoles located at the
      focal point of the lens with orthogonal oscillation directions and quadrature
      phase. The calculated pupil fields are experimentally generated with a vectorial
      optical field generator. The produced photonic spin orientations are
      quantitatively evaluated by their spin densities according to the tightly focused
      electric fields calculated by Richard-Wolf vectorial diffraction theory to
      demonstrate the validity and capability of the proposed technique.

PMID- 29041146
TI  - Investigation of bandwidth loading in optical fibre transmission using amplified
      spontaneous emission noise.
AB  - The use of spectrally shaped amplified spontaneous emission noise (SS-ASE) as a
      method for emulating interfering channels in optical fibre transmission systems
      has been studied. It is shown that the use of SS-ASE leads to a slightly
      pessimistic performance relative to the use of conventionally modulated
      interfering channels in the nonlinear regime. The additional nonlinear
      interference noise (on the channel under test), due to the Gaussian nature of SS
      ASE, has been calculated using a combination of the Gaussian noise (GN) and
      enhanced GN (EGN) models for the entire C-band (4.5 THz) and experimentally shown
      to provide a lower bound for transmission performance.

PMID- 29041147
TI  - Intensity of vortex modes carried by Lommel beam in weak-to-strong non-Kolmogorov
      turbulence.
AB  - We investigate the atmospheric turbulence effects on the propagation of vortex
      modes carried by Lommel beam. The analytic expression of the received signal and
      crosstalk mode intensity is derived based on the weak-to-strong non-Kolmogorov
      turbulence theory. The simulation results show that turbulence with small non
      Kolmogorov spectrum parameter, small inner-scale factor and large outer-scale
      factor is more likely to induce modal crosstalk. With the increment of turbulence
      strength, the crosstalk spreads from adjacent modes to peripheral modes. The
      received signal intensity can be improved by use of Lommel beam with small
      asymmetry parameter, low orbital angular momentum quantum number and long
      wavelength. The results are helpful to the design of orbital angular momentum
      based free-space optical communication link.

PMID- 29041148
TI  - Comparison between broadband Bessel beam launchers based on either Bessel or
      Hankel aperture distribution for millimeter wave short pulse generation.
AB  - In this paper, a comparison is presented between Bessel beam launchers at
      millimeter waves based on either a cylindrical standing wave (CSW) or a
      cylindrical inward traveling wave (CITW) aperture distribution. It is
      theoretically shown that CITW launchers are better suited for the generation of
      electromagnetic short pulses because they maintain their performances over a
      larger bandwidth than those realizing a CSW aperture distribution. Moreover, the
      wavenumber dispersion of both the launchers is evaluated both theoretically and
      numerically. To this end, two planar Bessel beam launchers, one enforcing a CSW
      and the other enforcing a CITW aperture distribution, are designed at millimeter
      waves with a center operating frequency of f-=60GHz and analyzed in the bandwidth
      50 - 70 GHz by using an in-house developed numerical code to solve Maxwell's
      equations based on the method of moments. It is shown that a monochromatic Bessel
      beam can be efficiently generated by both the launchers over a wide fractional
      bandwidth. Finally, we investigate the generation of limited-diffractive
      electromagnetic pulses at millimeter waves, up to a certain non-diffractive
      range. Namely, it is shown that by feeding the launcher with a Gaussian short
      pulse, a spatially confined electromagnetic pulse can be efficiently generated in
      front of the launcher.

PMID- 29041149
TI  - Quantum cascade lasers with Y2O3 insulation layer operating at 8.1 um.
AB  - SiO2 is a commonly used insulation layer for QCLs but has high absorption peak
      around 8 to 10 um. Instead of SiO2, we used Y2O3 as an insulation layer for DC
      QCL and successfully demonstrated lasing operation at the wavelength around 8.1
      um. We also showed 2D numerical analysis on the absorption coefficient of our DC
      QCL structure with various parameters such as insulating materials, waveguide
      width, and mesa angle.

PMID- 29041150
TI  - Magnetometry via spin-mechanical coupling in levitated optomechanics.
AB  - We analyze magnetometry using an optically levitated nanodiamond. We consider a
      configuration where a magnetic field gradient couples the mechanical oscillation
      of the diamond with its spin degree of freedom provided by a nitrogen vacancy
      center. First, we investigate the measurement of the position spectrum of the
      mechanical oscillator. We find that conditions of ultrahigh vacuum and feedback
      cooling allow a magnetic field gradient sensitivity of 1MUTm-1/Hz. At high
      pressure and room temperature, this sensitivity degrades and can attain a value
      of the order of 100mTm-1/Hz. Subsequently, we characterize the magnetic field
      gradient sensitivity obtainable by maneuvering the spin degrees of freedom using
      Ramsey interferometry. We find that this technique can offer photon-shot noise
      and spin-projection noise limited magnetic field gradient sensitivity of 100MUTm
      1/Hz. We conclude that this hybrid levitated nanomechanical magnetometer provides
      a favorable and versatile platform for sensing applications.

PMID- 29041151
TI  - Sb2S3 thickness-dependent lateral photovoltaic effect and time response observed
      in glass/FTO/CdS/Sb2S3/Au structure.
AB  - As an interesting one dimensional ribbon material, Sb2S3 has recently attracted
      much attention in recent years due to its exciting optical properties. However,
      Sb2S3-based photovoltaic or photoelectronic devices are still in research, and
      there are many things unknown to us and need to be well studied. In this work,
      the glass/FTO/CdS/Sb2S3/Au structures were successfully prepared with different
      Sb2S3 thicknesses, and the lateral photovoltaic effect (LPE) was firstly observed
      in this structure, suggesting its great potential in position sensitivity
      detectors (PSD). It is demonstrated that the crystallinity of Sb2S3 film
      increases, and Sb2S3 film tends to be vertical ribbon orientation with increasing
      thickness. Owing to the strong light absorption of the thicker Sb2S3 film and its
      one dimensional ribbon like crystal structure, the LPE in the
      glass/FTO/CdS/Sb2S3/Au structure improves with increasing Sb2S3 thickness from
      350 nm to 800 nm, and the glass/FTO/CdS/Sb2S3(800 nm) structure exhibits an
      unprecedented performance with position sensitivity as large as 2230.4 mV/mm.
      Moreover, the time response of photovoltage was also firstly measured in this
      structure, it is observed that both the rise time and the fall time decrease with
      increasing thickness from 350 nm to 800 nm, and then increase quickly for 1100 nm
      film, further verifing that the Sb2S3 thickness-dependent LPE is strongly
      dependent on the carriers' longitudinal transport time. The very large LPE and
      the relatively fast response speed observed in the glass/FTO/CdS/Sb2S3(800 nm)/Au
      structure unveils its great potential applications in the optoelectronic
      detectors and also bring an insight that the suitable thickness is very crucial
      in Sb2S3-based devices.

PMID- 29041152
TI  - Picosecond difference-frequency-generation in orientation-patterned gallium
      phosphide.
AB  - We report the generation of tunable high-repetition-rate picosecond radiation in
      the mid-infrared using the new quasi-phase-matched nonlinear material of
      orientation-patterned gallium phosphide (OP-GaP). The source is realized by
      single-pass difference-frequency-generation (DFG) between the output signal of a
      picosecond optical parametric oscillator (OPO) tunable across 1609-1637 nm with
      input pump pulses at 1064 nm in OP-GaP, resulting in tunable radiation across
      3040-3132 nm. Using a 40-mm-long crystal, we have generated up to 57 mW of DFG
      average power at ~80 MHz repetition rate for a pump power of 5 W and signal power
      of 0.9 W, with >30 mW over >50% of the tuning range. The DFG source exhibits a
      passive power stability better than 3.2% rms over 1 hour in good spatial beam
      quality. To the best of our knowledge, this is the first picosecond frequency
      conversion source based on OP-GaP.

PMID- 29041153
TI  - Cladding-like waveguide fabricated by cooperation of ultrafast laser writing and
      ion irradiation: characterization and laser generation.
AB  - We report the surface cladding-like waveguide fabricated by the cooperation of
      the ultrafast laser writing and the ion irradiation. The ultrafast laser writes
      tracks near the surface of the Nd:YAG crystal, constructing a semi-circle
      columnar structure with a decreased refractive index of - 0.00208. Then, the
      Nd:YAG crystal is irradiated by the Carbon ion beam, forming an enhanced-well in
      the semi-circle columnar with an increased refractive index of + 0.0024. Tracks
      and the enhanced-well consisted a surface cladding-like waveguide. Utilizing this
      cladding-like waveguide as the gain medium for the waveguide lasing, optimized
      characterizations were observed compared with the monolayer waveguide. This work
      demonstrates the refractive index of the Nd:YAG crystal can be well tailored by
      the cooperation of the ultrafast laser writing and the ion irradiation, which
      provides an convenient way to fabricate the complex and multilayered photonics
      devices.

PMID- 29041154
TI  - Nonreciprocal optical properties of thermal radiation with SiC grating magneto
      optical materials.
AB  - We demonstrate the nonreciprocal optical phenomenon of SiC gratings on substrate
      in infrared band, in which the Lorentz-Drude equations of dielectric constant
      tensor are proposed to describe the nonreciprocal optical properties as magnetic
      field applied on the magneto-optical materials, under variable intensity and
      wavelength. Moreover, the properly designed geometrical factors are proposed, and
      the good nonreciprocal absorption properties of SiC in thermal radiation
      wavelength band are presented. The dependence of the absorptivity as a function
      of different structure parameters, such as thickness of different layers, filling
      ratios, is studied in details. Furthermore, the electric field intensity is also
      presented for understanding light coupling, propagation. Numerical evidence shows
      that the nonreciprocal absorption performance is sensitive to the incidence
      angle, as well as the magnetic field strength. The relative study is useful to
      the thermal radiative design in photovoltaic and optical instrument.

PMID- 29041155
TI  - Hadamard single-pixel imaging versus Fourier single-pixel imaging.
AB  - Single-pixel imaging which employs active illumination to acquire spatial
      information is an innovative imaging scheme and has received increasing
      attentions in recent years. It is applicable to imaging at non-visible
      wavelengths and imaging under low light conditions. However, single-pixel imaging
      has once encountered problems of low reconstruction quality and long data
      acquisition time. Hadamard single-pixel imaging (HSI) and Fourier single-pixel
      imaging (FSI) are two representative deterministic model based techniques. Both
      techniques are able to achieve high-quality and efficient imaging, remarkably
      improving the applicability of single-pixel imaging scheme. In this paper, we
      compare the performances of HSI and FSI with theoretical analysis and
      experiments. The results show that FSI is more efficient than HSI while HSI is
      more noise-robust than FSI. Our work may provide a guideline for researchers to
      choose suitable single-pixel imaging technique for their applications.

PMID- 29041156
TI  - Optical coherence tomography and non-linear microscopy for paintings - a study of
      the complementary capabilities and laser degradation effects.
AB  - This paper examines for the first time the potential complementary imaging
      capabilities of Optical coherence tomography (OCT) and non-linear microscopy
      (NLM) for multi-modal 3D examination of paintings following the successful
      application of OCT to the in situ, non-invasive examination of varnish and paint
      stratigraphy of historic paintings and the promising initial studies of NLM of
      varnish samples. OCT provides image contrast through the optical scattering and
      absorption properties of materials, while NLM provides molecular information
      through multi-photon fluorescence and higher harmonics generation (second and
      third harmonic generation). OCT is well-established in the in situ non-invasive
      imaging of the stratigraphy of varnish and paint layers. While NLM examination of
      transparent samples such as fresh varnish and some transparent paints showed
      promising results, the ultimate use of NLM on paintings is limited owing to the
      laser degradation effects caused by the high peak intensity of the laser source
      necessary for the generation of non-linear phenomena. The high intensity normally
      employed in NLM is found to be damaging to all non-transparent painting materials
      from slightly scattering degraded varnish to slightly absorbing paint at the
      wavelength of the laser excitation source. The results of this paper are
      potentially applicable to a wide range of materials given the diversity of the
      materials encountered in paintings (e.g. minerals, plants, insects, oil, egg,
      synthetic and natural varnish).

PMID- 29041157
TI  - Birefringent masks that are optimal for generating bottle fields: erratum.
AB  - A sign error in the handedness of the rotating eigenpolarization pattern is
      corrected. This correction implies that a bottle field can be produced using just
      a stress-engineered optical element, without the need for a half-wave plate.

PMID- 29041158
TI  - Dissipative soliton resonance mode-locked all-polarization-maintaining double
      clad Er:Yb fiber laser.
AB  - Our first demonstration of an all-PM fiber double clad erbium-ytterbium figure-8
      laser mode-locked in a dissipative soliton resonance regime is presented. The
      laser generated uJ-level rectangular-shaped pulses with a maximum average output
      power of 1 W at 994 kHz repetition rate. The proposed configuration was
      characterized for two values resonator lengths - 44 and 205 m (total net
      dispersion -0.9274 ps2 and -4.3084 ps2, respectively) to verify the possibility
      of non-complex tailoring of pulse parameters. The long-term stability of the all
      PM configuration and self-starting of the mode-locking was experimentally
      confirmed by exposing the laser to forces of -5G to 7G magnitude on a vibration
      generator.

PMID- 29041159
TI  - On chip chirality-distinguishing beamsplitter.
AB  - The chirality of photons plays a fundamental role in light-matter interactions.
      However, a limiting factor in photonic integrated circuits is the lack of a
      miniaturized component, which can distinguish the chirality in a low cost and
      integrated manner. Herein we numerically demonstrate a chirality-distinguishing
      beamsplitter that can address this challenge. It consists of an integrated
      polarization rotator and a linear polarization beamsplitter, which together can
      fulfill the task of distinguishing and splitting left- and right-handed quasi
      circularly polarized modes on a chip with an ultra-broadband operation range from
      1.45 MUm to 1.65 MUm. Owning to the reciprocity, the device can emit photons with
      selectable spin angular momentum depending on the chosen feeding waveguide. The
      device is compatible with complementary metal-oxide semiconductor technology and
      it may open up new avenues in the fields of on-chip nano-photonics, bio-photonics
      and quantum information science.

PMID- 29041160
TI  - Multi-wavelength lenses for terahertz surface wave.
AB  - Metasurface-based surface wave (SW) devices working at multi-wavelength has been
      continuously arousing enormous curiosity recently, especially in the terahertz
      community. In this work, we propose a multi-layer metasurface structure composed
      of metallic slit pairs to build terahertz SW devices. The slit pair has a narrow
      bandwidth and its response frequency can be altered by its geometric parameter,
      thereby suppressing the frequency crosstalk and reducing the difficulty of
      design. By elaborately tailoring the distribution of the slit pairs, a series of
      achromatic SW lenses (SWLs) working at 0.6, 0.75 and 1 THz are experimentally
      demonstrated by the near field scanning terahertz microscope (NSTM) system. In
      addition, a wavelength-division-multiplexer (WDM) is further designed and
      implemented, which is promising in building multiplexed devices for plasmonic
      circuits. The structure proposed here cannot only couple the terahertz wave from
      free space to SWs, but also control its propagation. Moreover, our findings
      demonstrate the great potential to design multi-wavelength plasmonic metasurface
      devices, which can be extended to microwave and visible frequencies as well.

PMID- 29041161
TI  - Single-frequency fiber amplifier at 1.5 um with 100 W in the linearly-polarized
      TEM00 mode for next-generation gravitational wave detectors.
AB  - Next-generation gravitational wave detectors require single-frequency and high
      power lasers at a wavelength of 1.5 um addressing a set of demanding requirements
      such as linearly-polarized TEM00 radiation with low noise to run for long
      periods. In this context, fiber amplifiers in MOPA configuration are promising
      candidates to fulfill these requirements. We present a single-frequency
      monolithic Er:Yb co-doped fiber amplifier (EYDFA) at 1.5 um with a linearly
      polarized TEM00 output power of 100 W. The EYDFA is pumped off-resonant at 940 nm
      to enhance the Yb-to-Er energy transfer efficiency and enable higher ASE
      threshold. We also performed numerical simulations to investigate the off
      resonant pumping scheme and confirm the corresponding experimental results.

PMID- 29041162
TI  - Biaxial crystal beta-BaTeMo2O9: theoretical analysis and the feasibility as high
      efficiency acousto-optic Q-switch.
AB  - The high efficiency acousto-optic modulators become indispensable in photonics
      and optoelectronics for the pulse generation and signal modulation in optical
      display and telecommunications. In this paper, the validity and feasibility of
      the biaxial crystals as acousto-optic mediums have been theoretically analyzed
      and confirmed by experiments using a biaxial crystal of beta-BaTeMo2O9. The
      diffraction angle and diffraction efficiency of the beta-BaTeMo2O9 acousto-optic
      Q-switch are determined to be 1.420 degrees  and 78.1%, which are comparable with
      that of TeO2 acousto-optic modulator at the identical operating wavelength of
      1064 nm and 100 MHz, respectively. The minimum of the modulated pulse width can
      be achieved to be 6 ns at 5 kHz with Nd:YVO4 as the gain medium. The results not
      only provide an excellent acousto-optic medium, but also explore the field of
      biaxial acousto-optic medium for device fabrications.

PMID- 29041163
TI  - Passively mode-locked Yb fiber laser with PbSe colloidal quantum dots as
      saturable absorber.
AB  - A passively mode-locked Yb fiber laser using PbSe colloidal quantum dots (CQDs)
      as saturable absorber (SA) is experimentally demonstrated. An all-fiber
      experimental scheme was designed to understand the SA property of PbSe CQDs. The
      non-saturable loss, modulation depth, and saturable intensity of SA measured were
      23%, 7%, and 12 MW/cm2, respectively. The PbSe CQDs were sandwiched in a fiber
      connector, which was further inserted into the Yb fiber laser for mode-locking.
      As the pump power up to 110 mW, the self-starting mode-locking pulses were
      observed. Under the pump power of 285 mW, a maximum average laser power with
      fundamental mode-locking operation was obtained to be 21.3 mW. In this situation,
      the pulse full width at half maximum (FWHM), pulse repetition rate, and spectral
      FWHM were measured to be 70 ps, 8.3 MHz, and 4.5 nm, respectively.

PMID- 29041164
TI  - Effects of imperfect elements on resolution and sensitivity of quantum metrology
      using two-mode squeezed vacuum state.
AB  - It has been demonstrated that using two-mode squeezed vacuum state for phase
      estimation can break the Heisenberg limit. Our results reveal that the two-mode
      squeezed vacuum state is also applied to the optical rotation angle measurement.
      In our scheme, the resolution and sensitivity of the optical rotation angle
      signal are the same as the case of phase estimation. For the parameter
      estimation, phase or rotation angle, we discuss the influences of several
      imperfect factors on the resolution and sensitivity. First, the effect that the
      upper limit of photon-number resolving has on the maximum amount of available
      quantum Fisher information has been analyzed. Then, we have also studied the
      impacts of both the transmission efficiency in the transmission process and the
      detection efficiency on the detection results. Finally, conditions where all of
      the above imperfect elements are taken into account at the same time have also
      been explored. Additionally, other imperfect factors such as squeezing efficiency
      and dark counts are briefly discussed.

PMID- 29041165
TI  - Rotated echoes of molecular alignment: fractional, high order and imaginary.
AB  - We report experimental observations of rotated echoes of alignment induced by a
      pair of time-delayed and polarization-skewed femtosecond laser pulses interacting
      with an ensemble of molecular rotors. Rotated fractional echoes, rotated high
      order echoes and rotated imaginary echoes are directly visualized by using the
      technique of coincident Coulomb explosion imaging. We show that the echo
      phenomenon not only exhibits temporal recurrences but also spatial rotations
      determined by the polarization of the time-delayed second pulse. The dynamics of
      echo formation is well described by the laser-induced filamentation in rotational
      phase space. The quantum-mechanical simulation shows good agreements with the
      experimental results.

PMID- 29041166
TI  - Exponential fringe pattern projection approach to gamma-independent phase
      computation without calibration for gamma nonlinearity in 3D optical metrology.
AB  - This paper presents a method that expresses the fringe pattern as an exponential
      function and a mathematical model for gamma-independent phase computation. The
      method was compared to: (i) conventional phase measurement without nonlinearity
      correction, and (ii) conventional gamma correction by pattern pre-distortion
      based on an input-to-projector camera-output look-up table. The pre-distorted and
      exponential methods achieved large reduction in error compared to conventional
      computation with no gamma correction. The advantage of the exponential method is
      that no system gamma nonlinearity calibration procedure or information is
      required. This reduces optical system setup before measurement and permits easier
      use of off-the-shelf projectors.

PMID- 29041167
TI  - Optical biochemical sensor based on half-circled microdisk laser diode.
AB  - In this study, a half-circled cavity based microdisk laser diode is proposed and
      demonstrated experimentally for an integrated photonic biochemical sensor.
      Conventional microdisk sensors have limitations in optical coupling and
      reproducibility. In order to overcome these drawbacks, we design a novel half
      circled micro disk laser (HC-MDL) which is easy to manufacture and has optical
      output directionality. The Q-factor of the fabricated HC-MDL was measured as 7.72
      * 106 using the self-heterodyne method and the side mode suppression ratio was
      measured as 23 dB. Moreover, gas sensing experiments were performed using the HC
      MDL sensor. A wavelength shift response of 14.21 pm was obtained for 100 ppb
      dimethyl methylphosphonate (DMMP) gas and that of 14.70 pm was obtained for 1 ppm
      ethanol gas. These results indicate the possibility of highly sensitive gas
      detection at ppb levels using HC-MDL. This attractive feature of the HC-MDL
      sensor is believed to be very useful for a wide variety of optical biochemical
      sensor applications.

PMID- 29041168
TI  - Single-path Sagnac interferometer with Dove prism for orbital-angular-momentum
      photon manipulation.
AB  - Orbital angular momentum (OAM) is an important resource in high-dimensional
      quantum information processing, as its quantum number can be infinite. Dove prism
      (DP) is a most common tool to manipulate OAM light. However, the Dove prism
      changes the polarization of the photon states and decreases the sorting fidelity
      of the interferometer. In this work, we analyze the polarization-dependent effect
      of the DP on OAM light manipulation in the normal single-path Sagnac
      interferometers (SPSIs) with beam splitter (BS) and polarizing beam splitter
      (PBS). The results demonstrate that the BS SPSI is more sensitive to the input
      polarization and the specific parameters of the DP. We have also proposed and
      realized a modified BS SPSI, of which the sorting fidelity can be 100% in
      principle and is independent on the input polarization and the transmission
      matrix of the DP. The experiments demonstrate that the fidelity of the modified
      BS SPSI is about 5%~10% higher than that of the normal one. The modified BS SPSI
      is easy to implement (only two more half-wave plates are required) and is stable
      for free running at the scale of several hours. These merits make the structure
      suitable for applications in critical quantum information processing tasks, such
      as quantum cryptography.

PMID- 29041169
TI  - Planar waveguide moire grating.
AB  - We propose a new kind of planar waveguide Bragg grating structure, i.e., planar
      waveguide moire grating (MG), which is formed by two transverse adjacent gratings
      with slightly different Bragg wavelengths. It is found that this kind of
      structure shows the same light properties as the conventional MG that is realized
      by superimposing two Bragg gratings. Because the proposed MG structure is a
      planar pattern, the fabrication becomes much easier if applying a semiconductor
      microfabrication process, which is very beneficial for its applications in
      photonic integrated devices. Similar to the well-known Vernier effect, the
      coupling coefficient distribution can be easily adjusted by the alignment of the
      two adjacent gratings. Consequently, some special grating profiles can be
      achieved, such as perfect apodization with two sides of the coupling coefficient
      approaching zero. One important potential application of these specific features
      is the distributed feedback (DFB) semiconductor laser for improved properties,
      such as reduced spatial-hole burning and more power extraction. Some design
      examples are also given in this paper.

PMID- 29041170
TI  - Local phase method for designing and optimizing metasurface devices.
AB  - Metasurfaces have attracted significant attention due to their novel designs for
      flat optics. However, the approach usually used to engineer metasurface devices
      assumes that neighboring elements are identical, by extracting the phase
      information from simulations with periodic boundaries, or that near-field
      coupling between particles is negligible, by extracting the phase from single
      particle simulations. This is not the case most of the time and the approach thus
      prevents the optimization of devices that operate away from their optimum. Here,
      we propose a versatile numerical method to obtain the phase of each element
      within the metasurface (meta-atoms) while accounting for near-field coupling.
      Quantifying the phase error of each element of the metasurfaces with the proposed
      local phase method paves the way to the design of highly efficient metasurface
      devices including, but not limited to, deflectors, high numerical aperture
      metasurface concentrators, lenses, cloaks, and modulators.

PMID- 29041171
TI  - Bandwidth density as a figure of merit for few-mode multi-core fibers.
AB  - We investigated the relationships between the capacity limit and various figures
      of merit (spatial channel density, aggregate effective area ratio to cladding
      area, and bandwidth density) of few-mode multi-core fibers (FM-MCFs) where the
      modes in each core are weakly coupled. The capacity limit was estimated based on
      the Gaussian noise model for nonlinear impairment of single-mode fibers by
      neglecting crosstalk and intermodal nonlinear effects for simplicity; therefore,
      the estimated capacity can be the upper bound of the weakly-coupled FM-MCF
      capacity. When we take account of the transmission wavelength band of the FM-MCFs
      and the wavelength band where efficient amplification is available, the bandwidth
      density had a good correlation to the estimated capacity, but the spatial channel
      density and the aggregate effective area ratio often overestimate the FM-MCF
      capacity. Thus, we propose the bandwidth density for the figure of merit of FM
      MCFs rather than the spatial channel density or the aggregate effective area
      ratio. We also investigated the relationship between the bandwidth density and
      fiber design, and found that the supporting transmission bandwidth and the core
      count are the dominant factors for the bandwidth density, and the mode count per
      core has a small impact for the bandwidth density, when the core Delta is fixed.

PMID- 29041172
TI  - Efficient block-wise algorithm for compressive holography.
AB  - Compressive holography is a relatively time-consuming image estimation in convex
      optimized problem. We propose an efficient block-wise algorithm to limit the
      searching space and reduce the calculation time while keeping the reconstruction
      quality. The effective anti-aliasing boundary of the sub-hologram is located to
      determine the block size for compressive reconstruction in the total-variation
      two-step iterative shrinkage/thresholding algorithm. Padded sub-holograms could
      be reconstructed in parallel by using multi-core processors. Compared with the
      traditional compressive holography, the block-wise algorithm could take
      approximately 1/50 of the reconstruction time and achieve an improved
      reconstruction quality.

PMID- 29041173
TI  - Non-sky polarization-based dehazing algorithm for non-specular objects using
      polarization difference and global scene feature.
AB  - Photographic images taken in foggy or hazy weather (hazy images) exhibit poor
      visibility and detail because of scattering and attenuation of light caused by
      suspended particles, and therefore, image dehazing has attracted considerable
      research attention. The current polarization-based dehazing algorithms strongly
      rely on the presence of a "sky area", and thus, the selection of model parameters
      is susceptible to external interference of high-brightness objects and strong
      light sources. In addition, the noise of the restored image is large. In order to
      solve these problems, we propose a polarization-based dehazing algorithm that
      does not rely on the sky area ("non-sky"). First, a linear polarizer is used to
      collect three polarized images. The maximum- and minimum-intensity images are
      then obtained by calculation, assuming the polarization of light emanating from
      objects is negligible in most scenarios involving non-specular objects.
      Subsequently, the polarization difference of the two images is used to determine
      a sky area and calculate the infinite atmospheric light value. Next, using the
      global features of the image, and based on the assumption that the airlight and
      object radiance are irrelevant, the degree of polarization of the airlight (DPA)
      is calculated by solving for the optimal solution of the correlation coefficient
      equation between airlight and object radiance; the optimal solution is obtained
      by setting the right-hand side of the equation to zero. Then, the hazy image is
      subjected to dehazing. Subsequently, a filtering denoising algorithm, which
      combines the polarization difference information and block-matching and 3D (BM3D)
      filtering, is designed to filter the image smoothly. Our experimental results
      show that the proposed polarization-based dehazing algorithm does not depend on
      whether the image includes a sky area and does not require complex models.
      Moreover, the dehazing image except specular object scenarios is superior to
      those obtained by Tarel, Fattal, Ren, and Berman based on the criteria of no
      reference quality assessment (NRQA), blind/referenceless image spatial quality
      evaluator (BRISQUE), blind anistropic quality index (AQI), and e.

PMID- 29041174
TI  - Miniature all-optical probe for large synthetic aperture photoacoustic-ultrasound
      imaging.
AB  - A miniature all-optical probe for high-resolution photoacoustic (PA)-ultrasound
      (US) imaging using a large synthetic aperture is developed. The probe consists of
      three optical fibers for PA excitation, US generation, and detection of acoustic
      waves, respectively. The fiber for PA excitation has a large numerical aperture
      (NA) for wide-angle laser illumination. On the other hand, the fiber with a
      carbon black-polydimethylsiloxane composite coated on the end face of the optical
      fiber is used for wide-angle US transmission through laser-US conversion. Both
      the excited PA and backscattered US signals are detected by a fiber-tip Fabry
      Perot cavity for wide-angle acoustic detection. The probe outer diameter is only
      ~2 mm. The synergy of the three optical fibers makes a large-NA synthetic
      aperture focusing technique for high-resolution PA and US imaging possible. High
      PA lateral resolutions of 104-154 MUm and high US lateral resolutions of 64-112
      MUm over a depth range of > 4 mm are obtained. Compared with other existing
      miniature PA-US probes, to our knowledge, our probe achieves by far the best
      performance in terms of lateral resolutions and imaging depth range. The
      constructed probe has potential for endoscopic and intravascular imaging
      applications that require PA and US contrasts with high resolutions over a large
      depth range.

PMID- 29041175
TI  - Initial conditions for dissipative solitons in a strict polarization-controlled
      passively mode-locked Er-Fiber laser.
AB  - We report the dynamics of dissipative solitons in a ring cavity passively mode
      locked fiber laser with a strict control of the polarization state. We study the
      relation between the polarization state of the pulses propagating in the cavity
      and the regimes of generation. We have found that at pulse ellipticities between
      5 degrees  and 15 degrees , the laser generates one bunch of pulses in the
      cavity, while at higher ellipticities the laser generates multiple bunches. At
      constant ellipticity we rotated the polarization azimuth and observed a regime
      transition from the generation of noise-like pulses (NLP) to that of soliton
      crystal. The NLP regime was found when the azimuth was rotated towards smaller
      low-power transmission through the polarizer. The number of solitons in the
      soliton crystal also depended on the azimuth in a straightforward way: the higher
      the initial transmission, the bigger the number of solitons.

PMID- 29041176
TI  - Multi-subcarrier flexible bit-loading enabled capacity improvement in meshed
      optical networks with cascaded ROADMs.
AB  - We propose to use adaptive bit loading based on time-domain hybrid QAM (TDHQ) to
      maximize the capacity of subcarrier-multiplexing (SCM) systems in meshed optical
      networks with cascaded reconfigurable optical add and drop multiplexers (ROADMs).
      Note that the capacity is defined as the achievable net bit rate at the soft
      decision FEC threshold of BER = 2 * 10-2 in this work. The capacity improvement
      is first numerically and experimentally demonstrated in a 4-subcarrier SCM system
      with an aggregate symbol rate of 34.94 Gbaud. Compared with the conventional SCM
      system using uniform standard QAM, the proposed system can achieve an average
      capacity increase of 31.75% and 26.1% over various link conditions in simulations
      and experiments, respectively. Furthermore, we demonstrate that the proposed SCM
      system can better approach the channel capacity in the presence of narrow inline
      optical filtering. An average capacity improvement of 7.59% is also reported over
      all 17 ROADMs cases from 1 to 17 by simulations at OSNR = 21 dB, compared with
      its single carrier counterpart using TDHQ.

PMID- 29041177
TI  - Optical hot-spots in boron-nitride nanotubes at mid infrared frequencies: one
      dimensional localization due to random-scattering.
AB  - We report experimental observations of optical hot-spots associated with surface
      phonon polaritons in boron nitride nanotubes. As revealed by near-field optical
      microscopy, the hot-spots have mode volumes as small as ?2.7*10-6lambda03
      (lambda0 is the wavelength of the exciting light in vacuum), which are in the
      deep subwavelength regime. Such strong light-trapping leads to ultrahigh field
      enhancement with a Purcell factor of ?1.8 * 106. Remarkably, the hot-spots are
      not induced by designed structures, but by random scatterings with the rough gold
      substrate. The ultrahigh field enhancement can be used to improve nonlinear
      infrared spectroscopy, thermal emitters and detectors, and label-free molecule
      sensing at nanoscales.

PMID- 29041178
TI  - Electrically tunable two-dimensional metasurfaces at near-infrared wavelengths.
AB  - A novel, electrically tunable metasurface comprising a periodic array of disk
      shaped silicon resonators is proposed. The dielectric resonators can be
      individually manipulated by applying external bias, inducing the complex
      permittivity modulation of indium tin oxide (ITO) embedded in the middle of the
      silicon nanodisks. Simulation data shows a reflectance shift from 61% to 8% at
      lambda = 1111nm and a phase shift of 272.9 degrees  at lambda = 1127nm with an
      applied voltage in the range of -4 ~4V. In addition, by simply adjusting the
      resonator geometry, any operating wavelength from 850nm to 1150nm can be achieved
      with the metasurface.

PMID- 29041179
TI  - Polarisation structuring of broadband light.
AB  - Spatial structuring of the intensity, phase and polarisation of light is useful
      in a wide variety of modern applications, from microscopy to optical
      communications. This shaping is most commonly achieved using liquid crystal
      spatial light modulators (LC-SLMs). However, the inherent chromatic dispersion of
      LC-SLMs when used as diffractive elements presents a challenge to the extension
      of such techniques from monochromatic to broadband light. In this work we
      demonstrate a method of generating broadband vector beams with dynamically
      tunable intensity, phase and polarisation over a bandwidth of 100 nm. We use our
      system to generate radially and azimuthally polarised vector vortex beams
      carrying orbital angular momentum, and beams whose polarisation states span the
      majority of the Poincare sphere. We characterise these broadband vector beams
      using spatially and spectrally resolved Stokes measurements, and detail the
      technical and fundamental limitations of our technique, including beam generation
      fidelity and efficiency. The broadband vector beam shaper that we demonstrate
      here may find use in applications such as ultrafast beam shaping and white light
      microscopy.

PMID- 29041180
TI  - Generalized pupil function of a compound X-ray refractive lens.
AB  - Quality of a refractive compound X-ray lens can be limited by imperfections in
      surfaces of unit lenses and stacking precision. In general case both the lens
      transmission and optical aberrations define properties of a beam in the lens exit
      plane; together they can be expressed in terms of the generalized pupil function.
      In this work we measure this function for a diamond single crystal compound
      refractive lens. Consequently, we apply the pupil function to evaluate the
      performance of the examined compound refractive X-ray lens. A number of
      practically important conclusions can be drawn from such analysis.

PMID- 29041181
TI  - Optical modeling based on mean free path calculations for quantum dot phosphors
      applied to optoelectronic devices: comment.
AB  - A recent publication by Shin et al. [Opt. Express25, A113 (2017)] contains an
      optical simulation model for the quantum dots (QDs) nanophosphor based on the
      mean free path concept. We show that their measured scattering pattern of QDs is
      misleading, which would result in a fatal deviation between simulated and actual
      values.

PMID- 29041183
TI  - Enhancement of higher-order plasmonic modes in a dense array of split-ring
      resonators.
AB  - It is demonstrated that higher-order plasmonic modes in the split-ring resonators
      (SRRs) are strongly enhanced when SRRs are arranged in a densely spaced two
      dimensional array. The mode enhancement results from the near-field electrical
      coupling between the adjacent resonators. The effect is most pronounced in narrow
      gap SRRs which allows to observe experimentally plasmon modes up to the seventh
      order. In the array of narrow gap SRRs, the fifth-order resonance demonstrates
      high Q-factor, high resonance strength and wide tunability which opens up
      attractive features for practical applications of planar SRR structures.

PMID- 29041182
TI  - Influence of an Al2O3 surface coating on the response of polymeric waveguide
      sensors.
AB  - The responses of a polymer ridge waveguide Young interferometer with and without
      a bilayer of Al2O3/TiO2, fabricated by atomic layer deposition, are studied and
      compared when applied as an aqueous chemical sensor. The phase shift of the
      guided mode, as a result of the change in refractive index of the cover medium,
      is monitored. The results indicate that the over-coating affects the linearity of
      the sensor response. The effect of concentration on the linearity of the sensor
      response is investigated by applying different concentrations of water-ethanol
      solution. Although the performance of the sensor is improved by the additional
      layers, the study reveals a non-monotonic behavior of the device. We show that it
      comes mainly from the adsorption of ethanol molecules on the surface of the
      films. Such an understanding of the platform is crucial for sensing of analytes
      involving polar molecules.

PMID- 29041184
TI  - Free-standing double-layer terahertz band-pass filters fabricated by femtosecond
      laser micro-machining.
AB  - We report on the fabrication and transmission properties of free-standing single
      layer and double-layer THz bandpass filters. These filters are fabricated on
      aluminum foils using femtosecond laser micro-machining. The aluminum foils are
      periodically patterned with cross apertures with a total area of 1.75*1.75 cm2,
      also known as frequency-selective surfaces. Their terahertz transmission
      properties were simulated using the FDTD method and measured using a time-domain
      terahertz spectroscopy system. The simulation results agree with the measurements
      results very well. The performance of single-layer bandpass filters is as good as
      the commercial equivalents on the market. The double-layer filters show
      extraordinary transmission peaks with changing spacing between the two layers. We
      show the contour map of the electric field distribution across the apertures, and
      ascribe the new transmission peaks to the interference and coupling of surface
      plasmon polaritons between the two layers.

PMID- 29041185
TI  - Measurement-based meshing, basis selection, and prior assignment in chemical
      species tomography.
AB  - Gas distributions imaged by chemical species tomography (CST) vary in quality due
      to the discretization scheme, arrangement of optical paths, errors in the
      measurement model, and prior information included in reconstruction. There is
      currently no mathematically-rigorous framework for comparing the finite bases
      available to discretize a CST domain. Following from the Bayesian formulation of
      tomographic inversion, we show that Bayesian model selection can identify the
      mesh density, mode of interpolation, and prior information best-suited to
      reconstruct a set of measurement data. We validate this procedure with a
      simulated CST experiment, and generate accurate reconstructions despite limited
      measurement information. The flow field is represented using the finite element
      method, and Bayesian model selection is used to choose between three forms of
      polynomial support for a range of mesh resolutions, as well as four priors. We
      show that the model likelihood of Bayesian model selection is a good predictor of
      reconstruction accuracy.

PMID- 29041186
TI  - Broadband, efficient, and robust quasi-parametric chirped-pulse amplification.
AB  - Quasi-parametric chirped pulse amplification (QPCPA) is a new scheme that enables
      the amplification of chirped signal pulses without back conversion by depleting
      the idler pulses. In this paper, we present a numerical study on the bandwidth,
      efficiency, and robustness of QPCPA. Self-locked phase among the interacting
      waves is found to be the underlying mechanism for the suppression of back
      conversion, which allows signal efficiency approaching to the quantum limit even
      under the phase-mismatch condition, and thus greatly increases the phase-mismatch
      tolerance of QPCPA. We demonstrate that QPCPA can break through the trade-off
      between the efficiency and bandwidth encountered in conventional optical
      parametric amplification, hence supporting highly efficient amplification of few
      cycle pulses.

PMID- 29041187
TI  - Solution of the inhomogeneous Maxwell's equations using a Born series.
AB  - An algorithm for the numerical solution of the inhomogeneous Maxwell's equations
      is presented. The algorithm solves the inhomogeneous vector wave equation of the
      electric field by writing the solution as a convergent Born series. Compared to
      two dimensional finite difference time domain calculations, solutions showing the
      same accuracy can be calculated more than three orders of magnitude faster.

PMID- 29041188
TI  - Optical gain analysis of GaAs-based InGaAs/GaAsSbBi type-II quantum wells lasers.
AB  - A novel active region design based on a type-II InGaAs/GaAsSbBi quantum wells on
      GaAs substrate is proposed and studied in this work. The band structures of the
      InGaAs/GaAsSbBi type-II quantum wells are studied based on a self-consistent 14
      band k.p model. The electronic and optical properties of dilute-bismide
      InGaAs/GaAsSbBi type-II quantum well structures are investigated theoretically.
      Moreover, the room temperature gain characteristics of the laser active region
      are studied with different Bi composition. The theoretical results indicate that
      adding Bi into InGaAs/GaAsSb type-II active regions on GaAs substrate extends the
      laser emission wavelength beyond 1550nm without sacrificing the peak gain value.
      It is shown that these type-II quantum well structures are suitable for 1550nm
      wavelength region operation at room temperature.

PMID- 29041189
TI  - 47-fs Kerr-lens mode-locked Cr:ZnSe laser with high spectral purity.
AB  - We report on a room-temperature Kerr-lens mode-locked Cr:ZnSe femtosecond laser
      operating at around 2.4 MUm emission wavelength. Self-starting nearly transform
      limited pulse trains with a minimum duration of 47 fs, corresponding to six
      optical cycles, and average output power of 0.25 W are obtained with repetition
      frequencies in the range from 140 to 300 MHz. The femtosecond pulse train is
      characterized by high-spectral purity and low time jitter.

PMID- 29041190
TI  - Differential optical shadow sensor for sub-nanometer displacement measurement and
      its application to drag-free satellites.
AB  - We present a method for 3D sub-nanometer displacement measurement using a set of
      differential optical shadow sensors. It is based on using pairs of collimated
      beams on opposite sides of an object that are partially blocked by it. Applied to
      a sphere, our 3-axis sensor module consists of 8 parallel beam-detector sets for
      redundancy. The sphere blocks half of each beam's power in the nominal centered
      position, and any displacement can be measured by the differential optical power
      changes amongst the pairs of detectors. We have experimentally demonstrated a
      displacement sensitivity of 0.87nm/Hz at 1 Hz and 0.39nm/Hz at 10 Hz. We describe
      the application of the module to the inertial sensor of a drag-free satellite,
      which can potentially be used for navigation, geodesy and fundamental science
      experiments as well as ground based applications.

PMID- 29041191
TI  - Eight-wave mixing parametrical amplification.
AB  - We investigate parametrically amplified eight-wave mixing (PA-EWM). The double
      dressed PA-four-wave mixing (PA-FWM) is the superposition of one PA-FWM process,
      two different PA-six-wave mixing (PA-SWM) processes (PA-SWM1 and PA-SWM2 with
      external dressing field 776nm and 795nm, respectively) and one PA-EWM process.
      When the phases among FWM, SWM1, SWM2 and EWM change from 0 to pi, the double
      dressed PA-FWM could gradually satisfy the pure enhancement (all 0), partial
      enhancement and suppression (mixture of 0 and pi), or pure suppression condition
      (all pi). The outcomes of the investigation can potentially contribute to the
      development of multi-channel quantum information processing and high dimensional
      stereoscopic imaging.

PMID- 29041192
TI  - Random medium model for producing optical coherence lattice.
AB  - Within the Markov approximation, we introduce a novel class of random media which
      can produce a scattered field with optical lattice patterns. It is shown that the
      array dimension, lobes intensity profile, and the periodicity of the optical
      lattice can be flexibly controlled by altering the correlation parameters of
      scattering potential of the random medium. In addition, a new method for
      designing random media is proposed. It is shown that the convolution of any two
      legitimate degrees of potential correlation can lead to a new degree of potential
      correlation corresponding to a new scattered intensity distribution. An example
      of a novel family of random media is cited to demonstrate the result.

PMID- 29041193
TI  - Achieving diffraction-limited nanometer-scale X-ray point focus with two crossed
      multilayer Laue lenses: alignment challenges.
AB  - We discuss misalignment-induced aberrations in a pair of crossed multilayer Laue
      lenses used for achieving a nanometer-scale x-ray point focus. We thoroughly
      investigate the impacts of two most important contributions, the orthogonality
      and the separation distance between two lenses. We find that misalignment in the
      orthogonality results in astigmatism at 45 degrees  and other inclination angles
      when coupled with a separation distance error. Theoretical explanation and
      experimental verification are provided. We show that to achieve a diffraction
      limited point focus, accurate alignment of the azimuthal angle is required to
      ensure orthogonality between two lenses, and the required accuracy is scaled with
      the ratio of the focus size to the aperture size.

PMID- 29041194
TI  - Highly efficient machining of non-circular freeform optics using fast tool servo
      assisted ultra-precision turning.
AB  - Freeform optics has been regarded as the next generation of the optical
      components, especially those with non-circular apertures are playing an
      increasingly significant role in scanning field and specialized optical system.
      However, there still exist challenges to machine non-circular optical freeform
      surface. This paper is focused on highly efficiently generating freeform surfaces
      with optical surface quality by ultra-precision turning using a fast tool servo
      (FTS). A systematic strategy of machining smooth freeform surfaces with
      rectangular aperture is proposed in this paper. The contour of freeform optics is
      decomposed and assigned to the motions of slide and FTS back-and-forth. An
      optimized model is established for deriving the profile of the rotational
      component to cater for the capacity of FTS. Tool path reconstruction is carried
      out to generate a smooth tool trajectory and modified the contour to cater for
      the stroke of FTS. Simulation is adopted to analyze the machining property of a
      typical rectangular freeform surface. A rectangular freeform surface is
      efficiently machined via the proposed method, where a micron level profile error
      and nanometric finish in Ra are realized. Characteristics of reflection are
      analyzed via experiment and simulation. Prospects of such machining approach are
      discussed to provide guidance to future study.

PMID- 29041195
TI  - Demonstration of Bessel-like beam with variable parameters generated using cross
      phase modulation.
AB  - We propose a new method to generate Bessel-like beam using cross-phase
      modulation. The hot rubidium atomic sample is shown to have the ability to vary a
      Gaussian beam (probe beam) into a Bessel-like beam when the sample is illuminated
      with a counter-propagating Gaussian beam (pump beam) tuned close to the atomic
      resonances. It is demonstrated that the Bessel-like beam exhibits self-healing
      after encountering an obstruction on the beam path. The parameters of the Bessel
      like beam are found to be easily adjusted by the pump beam power and sample
      temperature. Moreover, this method is even applicable to the probe beam of low
      power, having more practical value than the method using self-phase modulation
      which needs high input beam power. The merits of variable parameter, no
      requirement for input beam power, simple setup, and low cost would make this
      method of significance in a variety of applications, especially in those areas
      where Bessel beam power is needed to be low and parameter to be adjusted easily
      without changing the setup.

PMID- 29041196
TI  - Envilab: Measuring phytoplankton in-vivo absorption and scattering properties
      under tunable environmental conditions.
AB  - Optical remote sensing of phytoplankton draws on distinctive spectral features
      which can vary with both species and environmental conditions. Here, we present a
      set-up (Envilab) for growing phytoplankton under well-defined light, temperature
      and nutrient conditions. The custom-built light source enables creation of light
      with spectral composition similar to natural aquatic environments. Spectral
      tuning allows for light quality studies. Attenuation is monitored with a
      spectrometer in transmission mode. In combination with automated
      spectrophotometer and fluorimeter measurements, absorption and excitation
      emission-fluorescence spectra are recorded. The set-up opens the door for
      systematic studies on phytoplankton optical properties and physiology.

PMID- 29041197
TI  - Performance analysis of FSO communications under LOS blockage.
AB  - We analyze the performance of a free-space optical (FSO) link affected by
      atmospheric turbulence and line-of-sight (LOS) blockage. For this purpose, the
      atmospheric turbulence induced fading is modeled by the M distribution, which
      includes the Gamma-Gamma distribution as special case. We exploit the fact that
      the physical interpretation of the M distribution allows to split the optical
      energy through the propagation link into three different components: two coherent
      components and one incoherent scatter component. Based on this separation, we
      derive novel analytical expressions for the probability density function (PDF),
      for the cumulative distribution function (CDF) and for the moment generating
      function (MGF) of the M distribution under the temporary blockage of the coherent
      components, hereinafter referred to as LOS blockage. Further, a new closed-form
      expression for the outage probability (OP) under LOS blockage is derived in terms
      of the turbulence model parameters and the LOS blockage probability. By means of
      an asymptotic analysis, this expression is simplified in the high-SNR regime and
      the OP in terms of the diversity order and diversity gain is then deduced.
      Obtained results show that the impact of the LOS blockage on the OP strongly
      depends on the intensity of the turbulence and on the LOS blockage probability.

PMID- 29041198
TI  - Determination of optical properties of turbid medium from relative interstitial
      CW radiance measurements using the incomplete P3 approximation.
AB  - Interstitial determination of the tissue optical properties is important in
      biomedicine, especially for interstitial laser therapies. Continuous wave (CW)
      radiance techniques which examine light from multiple directions have been
      proposed as minimally invasive methods for determining the optical properties
      under an interstitial probe arrangement. However, both the fitting algorithm
      based on the P3 approximation and the analytical method based on the diffusion
      approximation (DA), which are currently used recovery algorithms, cannot extract
      the optical properties of tissue with low transport albedos accurately from
      radiance measurements. In this paper, we proposed an incomplete P3 approximation
      for the radiance, the P3in for short, which is the asymptotic part of the
      solution for the P3 approximation. The relative differences between the P3in and
      the P3 were within 0.48% over a wide range of clinically relevant optical
      properties for measurements at source detector separations (SDS) from 5 mm to 10
      mm and angles from 0 degrees  to 160 degrees . Based on the P3in, we developed an
      analytical method for extracting the optical properties directly using simple
      expressions constructed from the radiance measurements at only two SDSs and four
      angles. The developed recovery algorithm was verified by simulated and
      experimental radiance data. The results show that both the absorption and reduced
      scattering coefficients were recovered accurately with relative errors within
      5.28% and 3.86%, respectively, from the simulated data and with relative errors
      within 10.82% and 10.67%, respectively, from the experimental data over a wide
      range of albedos from 0.5 to 0.99. Since the developed P3in-based radiance
      technique can obtain the optical properties rapidly from the measurements at only
      two SDSs and four angles, it is expected to be used for in vivo and in situ
      determination of the optical properties in online treatment planning during laser
      therapies.

PMID- 29041199
TI  - Spectral engineering of subwavelength-grating-based contradirectional couplers.
AB  - We tailor the spectral characteristics of silicon photonic contradirectional
      couplers (Contra-DCs), where the design of the coupler is based on placing a
      subwavelength grating (SWG) waveguide next to a strip waveguide. By tapering the
      gap distance between the SWG and strip waveguides, we demonstrate a compromise
      between sidelobe suppression and pass-band/stop-band extinction ratio such that
      the performance of the device as a potential optical (de)multiplexer is improved.
      The designs with different pass-band bandwidths of 12 nm, 9 nm, and 6 nm show 10
      dB to 20 dB sidelobe suppression ratio and 15 dB to 35 dB extinction ratio. We
      also obtain a resonant transmission peak in the stop-band of the spectral
      response of the device by introducing a pi phase shift into the gratings of the
      SWG waveguide. The resonant peak has 1 nm bandwidth and 7 dB extinction ratio,
      where the use of the SWG waveguide in the structure of such coupler allows the
      characteristics of the resonant peak to be highly sensitive to the cladding
      material, which is of strong desire in integrated sensing applications.

PMID- 29041200
TI  - Graphene metamaterial spatial light modulator for infrared single pixel imaging.
AB  - High-resolution and hyperspectral imaging has long been a goal for multi
      dimensional data fusion sensing applications - of interest for autonomous
      vehicles and environmental monitoring. In the long wave infrared regime this
      quest has been impeded by size, weight, power, and cost issues, especially as
      focal-plane array detector sizes increase. Here we propose and experimentally
      demonstrated a new approach based on a metamaterial graphene spatial light
      modulator (GSLM) for infrared single pixel imaging. A frequency-division
      multiplexing (FDM) imaging technique is designed and implemented, and relies
      entirely on the electronic reconfigurability of the GSLM. We compare our approach
      to the more common raster-scan method and directly show FDM image frame rates can
      be 64 times faster with no degradation of image quality. Our device and related
      imaging architecture are not restricted to the infrared regime, and may be scaled
      to other bands of the electromagnetic spectrum. The study presented here opens a
      new approach for fast and efficient single pixel imaging utilizing graphene
      metamaterials with novel acquisition strategies.

PMID- 29041201
TI  - Single lens logarithmic confocal distance measurement array.
AB  - This article presents a method and results based on confocal microscopy for non
      contact axial distance measurement from a lens to a partially reflective surface
      using an array of photodetectors. The ratio of the photodetector signals is
      independent of the surface reflectivity and light source variations over a range
      of distance. By using logarithmic photodetector signals the object distance is
      proportional to the difference between the signals. This technique potentially
      allows measurement of sound produced by single living cells, or the high velocity
      surface shape changes in the hohlraum in laser fusion experiments.

PMID- 29041202
TI  - Maximum a posteriori-based depth sensing with a single-shot maze pattern.
AB  - This study addressed the general problem of correspondence retrieval for single
      shot depth sensing where the coded features cannot be detected perfectly. The
      traditional correspondence retrieval technique can be regarded as maximum
      likelihood estimation with a uniform distribution prior assumption, which may
      lead to mismatches for two types of insignificant features: 1) incomplete
      features that cannot be detected completely because of edges, tiny objects, and
      many depth variations, etc.; and 2) distorted features disturbed by environmental
      noise. To overcome the drawback of the uniform distribution assumption, we
      propose a maximum a posteriori estimation-based correspondence retrieval method
      that uses the significant features as priors to estimate the weak or missing
      features. We also propose a novel monochromatic maze-like pattern, which is more
      robust to ambient illumination and the colors in scenes than the traditional
      patterns. Our experimental results demonstrate that the proposed system performs
      better than the popular RGB-D cameras and traditional single-shot techniques in
      terms of accuracy and robustness, especially with challenging scenes.

PMID- 29041203
TI  - Span length and information rate optimisation in optical transmission systems
      using single-channel digital backpropagation.
AB  - The optimisation of span length when designing optical communication systems is
      important from both performance and cost perspectives. In this paper, the
      optimisation of inter-amplifier spacing and the potential increase of span length
      at fixed information rates in optical communication systems with practically
      feasible nonlinearity compensation schemes have been investigated. It is found
      that in DP-16QAM, DP-64QAM and DP-256QAM systems with practical transceiver noise
      limitations, single-channel digital backpropagation can allow a 50% reduction in
      the number of amplifiers without sacrificing information rates compared to
      systems with optimal span lengths and linear compensation.

PMID- 29041204
TI  - Dual focus polarisation splitting lens.
AB  - We have successfully designed and measured a unique polarisation splitting lens
      which focuses the orthogonal linear polarisations side-by-side in the lens focal
      plane. This concept can find application in situations where there is limited
      space for the beam splitters and focusing optics that are required for incoherent
      detectors.

PMID- 29041205
TI  - Mid-infrared light emission > 3 um wavelength from tensile strained GeSn
      microdisks.
AB  - GeSn alloys with Sn contents of 8.4 % and 10.7 % are grown pseudomorphically on
      Ge buffers on Si (001) substrates. The alloys as-grown are compressively
      strained, and therefore indirect bandgap. Undercut GeSn on Ge microdisk
      structures are fabricated and strained by silicon nitride stressor layers, which
      leads to tensile strain in the alloys, and direct bandgap photoluminescence in
      the 3-5 um gas sensing window of the electromagnetic spectrum. The use of
      pseudomorphic layers and external stress mitigates the need for plastic
      deformation to obtain direct bandgap alloys. It is demonstrated, that the
      optically pumped light emission overlaps with the methane absorption lines,
      suggesting that GeSn alloys are well suited for mid-infrared integrated gas
      sensors on Si chips.

PMID- 29041206
TI  - Fifteen meter long uninterrupted filaments from sub-terawatt ultraviolet pulse in
      air.
AB  - A technique is presented to create uninterrupted long ultraviolet filaments in
      air using appropriately structured transmission mesh. The mesh with different
      cell sizes was inserted into 10-cm parallel beam of 0.2-J, 248-nm, and 870-fs
      pulse propagating along ~100-m corridor. Transverse positions of multiple
      filaments formed by the optimum size cells were reproducible within at least 15 m
      along the propagation path. 3D+time simulations confirmed uninterrupted plasma
      channels with fixed positions in the transverse space similar to the experiment.
      Unoptimized cell size resulted in filaments shifting towards the cell center and
      destruction of uninterrupted filaments.

PMID- 29041207
TI  - Complex beam shaping by cascaded conical diffraction with intercalated
      polarization transforming elements.
AB  - Cascaded conical diffraction where optical elements modifying the local
      polarization state are intercalated between the aligned biaxial crystals is
      analyzed theoretically in the framework of paraxial diffraction theory. The
      obtained expressions are verified and confirmed experimentally for the case of a
      two-crystal cascade intercalated by a polarizer or a wave plate. The present
      approach can be used to realize a variety of vector beams with complex beam
      shapes composed of concentric rings with strongly modulated azimuthal intensity
      distribution. A potentially very fast switching of the overall beam shape is
      possible if the intercalated elements are electro-optically tunable retarders.

PMID- 29041208
TI  - Passive compensation of laser-induced higher-order aberrations in high-power NIR
      optics.
AB  - We report a method for passive compensation of thermally induced focal shifts and
      higher-order aberrations of NIR laser processing optics. Theoretical
      considerations are made on the elimination of aberrations including polarization
      effects using a multi-stage compensation element with optical flats of both
      positive and negative dn/dT. A compensation layout is designed and optimized
      utilizing numerical simulations of thermo-optic effects. Based on these findings,
      optical elements for compensation of an F-Theta objective are manufactured. By
      means of wavefront measurements and beam caustic measurements the feasibility of
      simultaneous passive compensation of focal shifts and higher-order aberrations is
      demonstrated.

PMID- 29041209
TI  - Structure of polarization singularities of a light beam at triple frequency
      generated in isotropic medium by singularly polarized beam.
AB  - The components of electric field of the third harmonic beam, generated in
      isotropic medium with cubic nonlinearity by a monochromatic light beam carrying
      polarization singularity of an arbitrary type, are found analytically. The
      relation between C-points characteristics in the fundamental and signal beams are
      determined, as well as the impact of the phase mismatch on the shape of the C
      lines.

PMID- 29041210
TI  - 910-m propagation of THz ps pulses through the Atmosphere.
AB  - We measured the atmospheric propagation of ps THz pulses with a 0.4-THz bandwidth
      through a 910-m distance; the pulse delay corresponded to 255 pulses down the
      pulse train of the mode-locked ring laser excitation pulses. The complexity of
      the atmosphere requires the use of the complete theory of Essen and Froome to
      compare the measured time shifts due to both the dry atmosphere and water vapor
      with theoretical calculations. A new procedure involving the measurement of phase
      in the frequency domain is introduced and achieves comparable results for the
      calculated time shifts, compared to the previous direct measurements of time
      shifts. When the THz pulses were sequentially measured for a distance of 186 and
      910 m at the same weather condition, the time variation due to atmospheric
      turbulence between the two pulses of the 910 m measurement was up to 4 times
      larger than that between the two pulses of the 186 m measurement. THz long path
      WVD studies are necessary to evaluate proposed applications in the atmosphere,
      such as communications and monitoring pollutants and dangerous gases.

PMID- 29041211
TI  - Through-the-coating femtosecond laser inscription of very short fiber Bragg
      gratings for acoustic and high temperature sensing applications.
AB  - Very short Type I and Type II Bragg gratings, on the order of 100 um in length,
      are written through the protective polyimide coating of high NA and standard
      single mode silica optical fibers with infrared femtosecond pulses and a phase
      mask. By exploiting the transverse walk-off of apertured diffracted beams
      produced by the phase mask and a slit placed proximate the mask, complex grating
      structures are fabricated and characterized. These gratings are suitable for
      structural health monitoring based on acoustic measurements or localized high
      temperature measurements.

PMID- 29041212
TI  - Analogue of double-Lambda-type atomic medium and vector plasmonic dromions in a
      metamaterial.
AB  - We consider an array of the meta-atom consisting of two cut-wires and a split
      ring resonator coupled with an electromagnetic field with two polarization
      components. We show that the system can be taken as a classical analogue of the
      atomic medium of a double-Lambda-type four-level configuration coupled with four
      laser fields and working under the condition of electromagnetically induced
      transparency, exhibits an effect of plasmon induced transparency (PIT), and
      displays a similar behavior of atomic four-wave mixing (FWM). We show also that
      with the PIT and FWM effects the system can support vector plasmonic dromions
      when a nonlinear varactor is mounted onto the each gap of the split-ring
      resonator. Our work not only gives a plasmonic analogue of the FWM in coherent
      atomic systems but also provides the possibility for obtaining new type of
      plasmonic excitations in metamaterials.

PMID- 29041213
TI  - Very large photoresponsiviy and high photocurrent linearity for Ge-dot/SiO2/SiGe
      photoMOSFETs under gate modulation.
AB  - We report a novel visible-near infrared photoMOSFET containing a self-organized,
      gate-stacking heterostructure of SiO2/Ge-dot/SiO2/SiGe-channel on Si substrate
      that is simultaneously fabricated in a single oxidation step. Our typical
      photoMOSFETs exhibit very large photoresponsivity of 1000-3000A/W at low optical
      power (< 0.1MUW) or large photocurrent gain of 103-108A/A with a wide dynamic
      power range of at least 6 orders of magnitude (nW-mW) linearity at 400-1250 nm
      illumination, depending on whether the photoMOSFET operates at VG = + 3- + 4.5V
      or -1- + 1V. Numerical simulations reveal that photocarrier confinement within
      the Ge dots and the SiGe channel modifies the oxide field and the surface
      potential of SiGe, significantly increasing photocurrent and improving linearity.

PMID- 29041214
TI  - Single cell three-channel wavelength division multiplexing in visible light
      communication.
AB  - This paper examines the design of a prototype of a single cell three-channel
      visible light communication (VLC) based on wavelength division multiplexing for a
      radio frequency (RF)-free indoor healthcare. For a low complexity application, a
      single red green blue (RGB)-type white light-emitting diode (LED) and a single
      color sensor are adopted. An active low pass filter is utilized for robust light
      detection to eliminate ambient light and low frequency noise. The incoming tri
      color lights are separated by an adopted color sensor and simultaneously
      demodulated by a receiver processor. Then, the collected data are monitored in
      real-time and analyzed to provide the necessary medical attention to the
      concerned patient.

PMID- 29041215
TI  - Simplified model of spectral absorption by non-algal particles and dissolved
      organic materials in aquatic environments.
AB  - Absorption by non-algal particles (NAP, ad) and colored dissolved organic matter
      (CDOM, ag) are frequently modeled by exponential functions of wavelength, either
      separately or as a sum. We present a new representation of NAP-plus-CDOM
      absorption adg based on the stretched exponential function adg(lambda) = A exp{
      [s(lambda - lambdao)]beta}, whose parameter beta can be considered a measure of
      optical heterogeneity. A double exponential representation of adg can be fit
      extremely well by a stretched exponential for all plausible parameter
      combinations, despite having one fewer free parameter than a double exponential.
      Fitting two published compilations of in situ adg data - one at low spectral
      resolution (n = 5, lambda = 412-555 nm) and one at high spectral resolution (n =
      201, lambda = 300-700 nm) - the stretched exponential outperforms the single
      exponential, double exponential, and a power law. We thereby conclude that the
      stretched exponential is the preferred model for adg absorption in circumstances
      when NAP and CDOM cannot be separated, such as in remote sensing inversions.

PMID- 29041216
TI  - Modeling of carrier transport in organic light emitting diode with random dopant
      effects by two-dimensional simulation.
AB  - To model the carrier transport in organic light-emitting diodes (OLEDs) with
      random dopant effects in the emitting layer, two-dimensional simulation was used.
      By including the Gaussian shape density of states and field-dependent mobility in
      the Poisson and drift-diffusion solver, the carrier transport, trapping in the
      dopant state, and radiative recombination were accurately modeled. To examine the
      model, the current-voltage characteristics of organic light-emitting devices were
      compared. The host material in the emitting layer was 2,2-bis(1-phenyl-1H
      benzo[d]imidazol-2-yl)biphenyl (BImBP), which was doped with bis[2-(4,6
      difluorophenyl)pyridinato-C2,N](picolinato)iridium(III) (FIrpic) at various
      concentrations. By including the random doping model, the trend of mobility was
      altered and the radiative efficiency fitted experimental values well.

PMID- 29041217
TI  - Generation of high-power spatially structured beams using vertical external
      cavity surface emitting lasers.
AB  - In this paper, we demonstrate the generation of high-power and spatially
      structured beams using vertical external cavity surface emitting lasers (VECSEL).
      At the fundamental wavelength, an intracavity mode-control element is first
      employed to generate a range of Hermite-Gaussian (HG) modes in a linear cavity.
      The same HG modes are then excited and frequency doubled in a V-cavity geometry
      to generate a rich variety of high-power spatially structured beams. The results
      compare well with our numerical modeling.

PMID- 29041218
TI  - Oil pollution discrimination by an inelastic hyperspectral Scheimpflug lidar
      system.
AB  - An inelastic hyperspectral Scheimpflug lidar system is developed for range
      resolved oil pollution detection and discrimination. A theory of system
      parametric design is built for aquatic circumstances, and laser-induced
      fluorescence spectra with an excitation wavelength of 446 nm are employed to
      detect oil pollution. Seven kinds of typical oil samples are tested and well
      distinguished using the principal component analysis (PCA) and linear
      discriminant analysis (LDA) methods. It has been shown that blue laser diodes
      (LD) have great potential for oil pollution detection, and our system could be
      further utilized for more applications in both marine and terrestrial
      environments.

PMID- 29041219
TI  - Stability of period-one (P1) oscillations generated by semiconductor lasers
      subject to optical injection or optical feedback.
AB  - We study the stability of period-one (P1) oscillations experimentally generated
      by semiconductor lasers subject to optical injection (OI) and by those subject to
      optical feedback (OF). With unique advantages of broad frequency tuning range and
      large sideband rejection ratio, P1 oscillations can be useful in applications
      such as photonic microwave generation, radio-over-fiber communication, and laser
      Doppler velocimeter. The stability of the P1 oscillations is critical for these
      applications, which can be affected by spontaneous emission and fluctuations in
      both temperature and injection current. Although linewidths of P1 oscillations
      generated by various schemes have been reported, the mechanisms and roles which
      each of the OI and the OF play have however not been investigated in detail. To
      characterize the stability of the P1 oscillations generated by the OI and the OF
      schemes, we measure the linewidths and linewidth reduction ratios (LRRs) of the
      P1 oscillations. The OF scheme has a narrowest linewidth of 0.21 +/- 0.03 MHz
      compared to 4.7 +/- 0.6 MHz in the OI scheme. In the OF scheme, a much larger
      region of LRRs higher than 90% is also found. The superior stability of the OF
      scheme is benefited by the fact that the P1 oscillations in the OF scheme are
      originated from the undamped relaxation oscillation of a single laser and can be
      phase-locked to one of its external cavity modes, whereas those in the OI scheme
      come from two independent lasers which bear no phase relation. Moreover, excess
      P1 linewidth broadening in the OI scheme caused by fluctuation in injection
      parameters associated with frequency jitter and relative intensity noise (RIN) is
      also minimized in the OF scheme.

PMID- 29041220
TI  - Thermally ruggedized ITO transparent electrode films for high power
      optoelectronics.
AB  - We present two strategies to minimize laser damage in transparent conductive
      films. The first consists of improving heat dissipation by selection of
      substrates with high thermal diffusivity or by addition of capping layer
      heatsinks. The second is reduction of bulk energy absorption by lowering free
      carrier density and increasing mobility, while maintaining film conductance with
      thicker films. Multi-pulse laser damage tests were performed on tin-doped indium
      oxide (ITO) films configured to improve optical lifetime damage performance.
      Conditions where improvements were not observed are also described. When bulk
      heating is not the dominant damage process, discrete defect-induced damage limits
      damage behavior.

PMID- 29041221
TI  - Modal noise in an integrated photonic lantern fed diffraction-limited
      spectrograph.
AB  - In an attempt to develop a streamlined astrophotonic instrument, we demonstrate
      the realization of an all-photonic device capable of both multimode to single
      mode conversion and spectral dispersion on an 8-m class telescope with efficient
      coupling. The device was a monolithic photonic spectrograph which combined an
      integrated photonic lantern and an efficient arrayed waveguide grating device.
      During on-sky testing, we discovered a previously unreported type of noise that
      made spectral extraction and calibration extremely difficult. The source of the
      noise was traced to a wavelength-dependent loss mechanism between the feed
      fiber's multimode near-field pattern and the modal acceptance profile of the
      integrated photonic lantern. Extensive modeling of the photonic components
      replicates the wavelength-dependent loss, and demonstrates an identical effect on
      the final spectral output. We outline that this could be mitigated by directly
      injecting into the integrated photonic lantern.

PMID- 29041222
TI  - Coherent detection of THz laser signals in optical fiber systems.
AB  - Terahertz (THz) coherent detectors are crucial for the stabilization and
      measurement of the properties of quantum cascade lasers (QCLs). This paper
      describes the exploitation of intra-cavity sum frequency generation to up-convert
      the emission of a THz QCL to the near infrared for detection with fiber optic
      coupled components alone. Specifically, a low cost infrared photodiode is used to
      detect a radio frequency (RF) signal with a signal-to-noise ratio of
      approximately 20dB, generated by beating the up-converted THz wave and a near
      infrared local oscillator. This RF beat note allows direct analysis of the THz
      QCL emission in time and frequency domains. The application of this technique for
      QCL characterization is demonstrated by analyzing the continuous tuning of the RF
      signal over 2 GHz, which arises from mode tuning across the QCL's operational
      current range.

PMID- 29041223
TI  - Optical constants and structural properties of thin gold films.
AB  - We report a comprehensive experimental study of optical and electrical properties
      of thin polycrystalline gold films in a wide range of film thicknesses (from 20
      to 200 nm). Our experimental results are supported by theoretical calculations
      based on the measured morphology of the fabricated gold films. We demonstrate
      that the dielectric function of the metal is determined by its structural
      morphology. Although the fabrication process can be absolutely the same for
      different films, the dielectric function can strongly depend on the film
      thickness. Our studies show that the imaginary part of the dielectric function of
      gold, which is responsible for optical losses, rapidly increases as the film
      thickness decreases for thicknesses below 80 nm. At the same time, we do not
      observe a noticeable dependence of optical constants on the film thickness for
      thicker samples. These findings establish design rules for thin-film plasmonic
      and nanophotonic devices.

PMID- 29041224
TI  - Curvature effect on polarization of light emitted from chiral carbon nanotubes.
AB  - We investigate that effect of the curvature on induced hybridization and
      modification of emission profiles for each chiral's index single-wall carbon
      nanotubes (SWCNTs). According to the Schwinger two particle pair state method, we
      provide an analytical expression by calculating polar of spot intensity as a
      function of the polar angle. The emission profiles for indirect transition have
      an asymmetric shape as a function of the electron wave vector of the axis
      direction kt and depend on the chiral index. Here we show polarization-dependent,
      given analytically by expanding the matrix element into the scalar product of the
      light polarization vector and the dipole vector. These scalar products having a
      maximum value depend on the summation of phase factors of spinors of electrons in
      the conduction band Phic and valence band Phiv. In the case of direct transition,
      dipole vector tube axis is maximum at the phase summation of Phic and Phiv is 0
      or 2pi. In contrast, the maximum dipole vector circumference is obtained at the
      phase summation of pi for the case of indirect transition. We can predict a
      strong emission peak and emission profiles which can be used to identify optical
      transitions in an individual SWCNT with different chiral indices experimentally.

PMID- 29041225
TI  - Photovoltaic Ge/SiGe quantum dot mid-infrared photodetector enhanced by surface
      plasmons.
AB  - We report the fabrication and characterization of a multilayer Ge quantum dot
      detector grown on Si1-xGex virtual substrate (x = 0.18) for photovoltaic mid-wave
      infrared photodetection. Detector displays an over 100% photovoltaic response
      enhancement as compared to a conventional Ge/Si device due to smaller hole
      effective mass in the SiGe barriers. A further enhancement in sensitivity is
      achieved by excitation of surface plasmon polariton waves in a Ge/SiGe
      photodetector coupled with a two-dimensional plasmonic structure. The plasmonic
      resonance induced photocurrent enhancement is found to be larger when the
      incident infrared light illuminates the detector from its substrate side. At zero
      bias and 90 K, the responsivity of 40 mA/W and peak detectivity of 1.4 * 1011
      cm.Hz1/2/W are determined at a wavelength of 4 um.

PMID- 29041226
TI  - Turbulence heterodyne coherent mitigation of orbital angular momentum
      multiplexing in a free space optical link by auxiliary light.
AB  - A novel scheme is proposed to mitigate the atmospheric turbulence effect in free
      space optical (FSO) communication employing orbital angular momentum (OAM)
      multiplexing. In this scheme, the Gaussian beam is used as an auxiliary light
      with a common-path to obtain the distortion information caused by atmospheric
      turbulence. After turbulence, the heterodyne coherent detection technology is
      demonstrated to realize the turbulence mitigation. With the same turbulence
      distortion, the OAM beams and the Gaussian beam are respectively utilized as the
      signal light and the local oscillation light. Then the turbulence distortion is
      counteracted to a large extent. Meanwhile, a phase matching method is proposed to
      select the specific OAM mode. The discrimination between the neighboring OAM
      modes is obviously improved by detecting the output photocurrent. Moreover, two
      methods of beam size adjustment have been analyzed to achieve better performance
      for turbulence mitigation. Numerical results show that the system bit error rate
      (BER) can reach 10-5 under strong turbulence in simulation situation.

PMID- 29041227
TI  - Polarization attraction of 10-Gb/s NRZ-BPSK signal in a highly nonlinear fiber.
AB  - Polarization attraction of a 10-Gb/s non-return-to-zero binary phase-shift keyed
      (NRZ-BPSK) signal has been successfully demonstrated for the first time in a
      counter-propagating beam configuration using a continuous-wave pump, in a highly
      nonlinear fiber, by utilizing the Kerr nonlinear cross-polarization process
      inherent to that fiber. The efficacy of mitigating polarization-dependent loss
      across polarization-sensitive devices was emulated with a linear polarizer
      located before the receiver. The receiver sensitivity penalty at 10-9 bit-error
      rate relative to the baseline NRZ-BPSK signal was < 0.5 dB, when polarization
      attraction was employed for a polarization-scrambled signal (after achieving a
      degree of polarization > 90%). The results confirm that polarization attraction
      is independent of modulation format.

PMID- 29041228
TI  - Orbital angular momentum mode groups multiplexing transmission over 2.6-km
      conventional multi-mode fiber.
AB  - Twisted light carrying orbital angular momentum (OAM) is a special kind of
      structured light that has a helical phase front, a phase singularity, and a
      doughnut intensity profile. Beyond widespread developments in manipulation,
      microscopy, metrology, astronomy, nonlinear and quantum optics, OAM-carrying
      twisted light has seen emerging application of optical communications in free
      space and specially designed fibers. Instead of specialty fibers, here we show
      the direct use of a conventional graded-index multi-mode fiber (MMF) for OAM
      communications. By exploiting fiber-compatible mode exciting and filtering
      elements, we excite the first four OAM mode groups in an MMF. We demonstrate 2.6
      km MMF transmission using four data-carrying OAM mode groups (OAM0,1, OAM+1,1/OAM
      1,1, OAM+2,1, OAM+3,1). Moreover, we demonstrate two data-carrying OAM mode
      groups multiplexing transmission over the 2.6-km MMF with low-level crosstalk
      free of multiple-input multiple-output digital signal processing (MIMO-DSP). The
      demonstrations may open up new perspectives to fiber-based OAM communication/non
      communication applications using already existing conventional fibers.

PMID- 29041229
TI  - Time-reversed and reciprocal second-harmonic generation with pump depletion.
AB  - The time-reversed second-harmonic generation in one-dimensional nonlinear
      photonic crystals has been theoretically studied without the undepleted pump
      approximation. A simple criterion has been deduced which determines the energy
      flow. Based on it, two kinds of structures with different symmetries are
      presented to realize the nonlinear time reversal effect. A completely reciprocal
      nonlinear response is also found in the same process. Furthermore, a multi
      section-cascaded structure is proposed to realize the nonlinear time reversal at
      any given position.

PMID- 29041230
TI  - Compact tunable electromagnetically induced transparency and Fano resonance on
      silicon platform.
AB  - We propose and demonstrate an on-chip coupling resonant system to generate
      electromagnetically induced transparency (EIT)-like effect and Fano resonance on
      silicon platform. It is composed of a microring resonator (MRR) and two cascaded
      Sagnac-loop mirrors (SLMs) assisted Fabry-Perot (FP) cavity on silicon-on
      insulator. According to the coupling conditions of the MRR, two cases are studied
      theoretically. When the MRR is over coupling, EIT-like transmission can be
      observed. In contrast, Fano resonances can be generated by the condition of under
      coupling. In the experiment, the add-drop MRR is under coupling, leading to a
      sharp asymmetric line shape for Fano resonance. The resonance wavelength of the
      MRR can be dynamically tuned based on thermal-optic effects by tuning the micro
      heater. The experiment results show Fano resonances with maximum extinction ratio
      (ER) of 23.22 dB and maximum slope rate (SR) of 252 dB/nm. Moreover, the
      wavelength of Fano resonance can be shifted widely with a tuning efficiency of
      0.2335 nm/mW.

PMID- 29041231
TI  - Bistable four-wave mixing response in a semiconductor quantum dot coupled to a
      photonic crystal nanocavity.
AB  - We perform a theoretical study of the bistable four-wave mixing (FWM) response in
      a coupled system comprised of a semiconductor quantum dot (SQD) and a photonic
      crystal (PC) nanocavity in which the SQD is embedded. It is shown that the shape
      of the FWM spectrum can switch among single-peaked, double-peaked, triple-peaked,
      and four-peaked arising from the vacuum Rabi splitting and the exciton-nanocavity
      coupling. Especially, we map out bistability phase diagrams within a parameter
      subspace of the system, and find that it is easy to turn on or off the bistable
      FWM response by only adjusting the excitation frequency or the pumping intensity.
      Our results offer a feasible means for measuring the SQD-PC nanocavity coupling
      strength and open a new avenue to design optical switches and memories.

PMID- 29041232
TI  - Mid-infrared optical properties of chalcogenide glasses within tin-antimony
      selenium ternary system.
AB  - In this work, we investigated the mid-infrared (MIR) optical properties of
      selenide (Se-based) chalcogenide glasses (ChGs) within an As- and Ge-free system,
      namely the environment-friendly and low-cost tin-antimony-selenium (Sn-Sb-Se,
      SSS) ternary system, which has not been systematically studied to the best of our
      knowledge. As compared to ChGs within those conventional Se-based systems, SSS
      ChGs were found to exhibit extended infrared transmittance range as well as
      larger linear refractive index (n0). Femtosecond Z-scan measurements show the
      presence of evident three-photon absorption from Urbach absorption of the SSS
      ChGs at MIR wavelength, which resonantly enhanced the nonlinear refractive
      behavior and resulted in large nonlinear refractive index (n2).

PMID- 29041233
TI  - Circular-core single-mode polymer waveguide for high-density and high-speed
      optical interconnects application at 1550 nm.
AB  - We demonstrate circular-core 1550 nm single-mode polymer waveguides with a graded
      index profile fabricated by commercially available UV-curable epoxies using so
      called mosquito method. The relative index difference ?n of the waveguides was
      designed to be 0.46% in order to guarantee both single-mode operation and good
      compatibility with standard single-mode fiber. Accurate refractive index tuning
      of monomer for core construction was realized by mixing the core and cladding
      epoxies properly. The core pitch of the waveguides was chosen to be 50 MUm to
      satisfy the requirements for high-density on-board optical interconnects. Both
      the optical characteristics and high-speed performances of the waveguides were
      comprehensively studied at 1550 nm. The measured transmission and coupling loss
      are 0.79 dB/cm and 0.78 dB, respectively. The waveguides exhibit an inter-channel
      crosstalk as low as -45 dB, and a 3 dB misalignment tolerance larger than +/- 4
      MUm on the input and output facet in both horizontal and vertical directions. NRZ
      signal at a data rate of 25 Gb/s was transmitted over a 10 cm-long waveguide.
      There is no obvious degradation on the eye diagram due to the insertion of the
      waveguide and error free transmission was successfully obtained. Our results
      imply that the fabricated single-mode polymer waveguides have good potential in
      high-density and high-speed optical interconnects application.

PMID- 29041234
TI  - Simultaneous generation of multiple vector beams on a single SLM.
AB  - Complex vector light fields, classically entangled in polarization and phase,
      have become ubiquitous in a wide variety of research fields. This has triggered
      the demonstration of a wide variety of generation techniques. Of particular
      relevance are those based on computer-controlled devices due to their great
      flexibility. In particular, spatial light modulators have demonstrated their high
      capabilities to generate any vector beam, with various spatial profiles and
      polarization distributions. Here, we put forward a novel technique that exploits
      the superposition principle in optics to enable the simultaneous generation of
      many vector beams using a single digital hologram. As proof-of-principle, we
      demonstrated the simultaneous generation of sixteen vector vortex beams with
      various polarization distributions and spatial shapes on a single SLM, each with
      their own spatial shape and polarization distribution.

PMID- 29041235
TI  - Crosstalk mitigation using pilot assisted least square algorithm in OFDM-carrying
      orbital angular momentum multiplexed free-space-optical communication links.
AB  - In this paper, we experimentally investigate the performance of crosstalk
      mitigation for 16-ary quadrature amplitude modulation orthogonal frequency
      division multiplexing (16QAM-OFDM) signals carrying orbital angular momentum
      (OAM) multiplexed free-space-optical communication (FSO) links using the pilot
      assisted Least Square (LS) algorithm. At the demodulating spatial light
      modulators (SLMs), we launch the distorted phase holograms which have the
      information of atmospheric turbulence obeying the modified Hill spectrum. And
      crosstalk can be introduced by these holograms with the experimental
      verification. The pilot assisted LS algorithm can efficiently improve the quality
      of system performance, the points of constellations get closer to the reference
      points and around two orders of magnitude improvement of bit-error rate (BER) is
      obtained.

PMID- 29041236
TI  - High responsivity coherent photonic receiver integrating an SOA, a 90 degrees 
      hybrid, and high speed UTC photodiodes.
AB  - We demonstrate a single polarization monolithically integrated coherent receiver
      on an InP substrate with a SOA preamplifier, a 90 degrees  optical hybrid, and
      four 40 GHz UTC photodiodes. Record performances with responsivity above 4 A/W
      with low imbalance <1 dB and error free detection of 32 Gbaud QPSK signals were
      simultaneously demonstrated.

PMID- 29041237
TI  - Gouy phase induced polarization transition of focused vector vortex beams.
AB  - We propose a common criterion for the effect of Gouy phase on the distinct
      polarization transition of focused vector vortex beams (VVBs). Such polarization
      transition is strongly dependent on the parity of the smaller modulus between
      VVB's polarization order and topological charge. Significantly, the cross
      polarization transitions are observed at areas where the two spin components with
      equi-intensity are exactly overlapping and the Gouy phase difference (GPD)
      between them equals to (2k + 1)pi, k is an integer. As a whole, the focal field
      shows radially variant polarization distributions resulting from the unequal
      intensity proportion of the two spin components. This polarization transition
      holds potential in modifying the patterns of periodic surface structure induced
      by femtosecond vector beams.

PMID- 29041238
TI  - Interferometer based on strongly coupled multi-core optical fiber for accurate
      vibration sensing.
AB  - We report on the use of a simple interferometer built with strongly-coupled core
      optical fiber for accurate vibration sensing. Our multi-core fiber (MCF) is
      designed to mode match a standard single-mode optical fiber (SMF). The
      interferometer consists of a low insertion loss SMF-MCF-SMF structure where only
      two super-modes interfere. The polymer coating of the MCF was structured and the
      interferometer was sandwiched between a flat piece and a V-groove. In this manner
      our device is highly sensitive to force with sensitivity reaching -4225 pm/N. To
      make the MCF interferometer sensitive to vibrations the flat piece was allowed to
      move, thus, its periodic movements exert cyclic localized pressure on the MCF
      which makes the interference pattern to shift periodically. Our sensors can be
      used to monitor vibrations in a broad frequency range with the advantage that the
      measurements are unaffected by temperature changes.

PMID- 29041239
TI  - Subcutaneous veins depth measurement using diffuse reflectance images.
AB  - Intravenous (IV) procedures are often difficult due to the poor visualization of
      subcutaneous veins. Because existing vein locators lack the ability to assess
      depth, and also because mis-punctures and poor vascular access remain
      problematic, we propose an imaging system that employs diffuse reflectance images
      at three isosbestic wavelengths to measure both the depth and thickness of
      subcutaneous veins. This paper describes the proposed system as well as proof-of
      principle experimental demonstrations. We initially introduce the working
      principle and structure of the system. All measurements were based on the Monte
      Carlo (MC) method and accomplished by referring an optical density (OD) ratio to
      a multi-layer diffuse reflectance model. Results were all validated by
      comparative ultrasound measurements. Experimental trials included 11 volunteers
      who were subjected to both ultrasound measurements and the proposed optical
      process to validate the system's applicability. However, the unreliability of the
      "thickness" measurement of the vein may be due to the fact that the veins have
      collapsible walls - so excess pressure by the transducer will give a false
      thickness.

PMID- 29041240
TI  - Diode-pumped Tm:KY(WO4)2 laser passively modelocked with a GaSb-SESAM.
AB  - We present the first diode-pumped modelocked thulium (Tm3+) laser based on a
      double-tungstate crystalline gain material. The solid-state laser consists of a
      Tm:KY(WO4)2 crystal as gain medium and a GaInSb/GaSb quantum well saturable
      absorber for self-starting passive mode locking. The laser is pumped by a multi
      mode fiber-coupled laser diode at a wavelength of 793 nm. An average output power
      of 202 mW is achieved at a center wavelength of 2032 nm. Pulses with duration of
      3 ps are generated at a repetition rate of 139.6 MHz. We also report on the first
      noise evaluation of a modelocked solid-state laser operating in the 2-um
      wavelength range. We measured a timing jitter of sub-100 fs and a relative
      intensity noise of only 0.04% (frequency range from 500 Hz to 1 MHz).

PMID- 29041241
TI  - Sub-picosecond laser damage growth on high reflective coatings for high power
      applications.
AB  - Growth of laser damage on High Reflection (HR) thin film coatings is investigated
      at the wavelength of 1.030um in the sub-picosecond regime. An experimental laser
      damage setup in a pump / probe configuration is used to study the growth behavior
      of engineered damage sites as well as laser damage sites. Results demonstrate
      that engineered sites and laser damage sites grow identically which indicates
      that the growth phenomenon is intrinsic to materials and stack design. In order
      to analyze the experimental results, we have developed a numerical model to
      simulate growth. Using FEM simulations, we demonstrate that growth is governed by
      the evolution of the electric field distribution in the mirror stack under the
      successive laser shots, which is supported by time-resolved observations of
      damage growth events. Eventually the results are compared to laser damage
      observations made on of full scale PETAL mirrors, which fully support the
      approach.

PMID- 29041242
TI  - Frequency-scanning interferometry using a time-varying Kalman filter for dynamic
      tracking measurements.
AB  - Frequency scanning interferometry (FSI) with a single external cavity diode laser
      (ECDL) and time-invariant Kalman filtering is an effective technique for
      measuring the distance of a dynamic target. However, due to the hysteresis of the
      piezoelectric ceramic transducer (PZT) actuator in the ECDL, the optical
      frequency sweeps of the ECDL exhibit different behaviors, depending on whether
      the frequency is increasing or decreasing. Consequently, the model parameters of
      Kalman filter appear time varying in each iteration, which produces state
      estimation errors with time-invariant filtering. To address this, in this paper,
      a time-varying Kalman filter is proposed to model the instantaneous movement of a
      target relative to the different optical frequency tuning durations of the ECDL.
      The combination of the FSI method with the time-varying Kalman filter was
      theoretically analyzed, and the simulation and experimental results show the
      proposed method greatly improves the performance of dynamic FSI measurements.

PMID- 29041243
TI  - Multiplexed coded time domain sampling with metamaterials.
AB  - The far infrared region of the electromagnetic spectrum often necessitates the
      use of thermal detectors that, by nature, typically have poor response times and
      diminished sensitivities, at least compared to adjacent bands. However, many
      signals of interest contain frequency components far too fast to be reliably
      measured with such detectors, and hence expensive and inefficient alternatives
      are brought to bear. Here we propose and experimentally validate a new method
      leveraging the speed and scalability of dynamic metamaterial modulators to encode
      high-frequency signal components at a lower frequency, making them reliably
      measurable with thermal detectors that would otherwise be too slow. An optimal
      weighing scheme design in the time domain is realized, the result being an
      imaging system whose time resolution is independent of detector speed and is
      rather limited only by the speed of the modulator and the reproducibility of the
      signal of interest.

PMID- 29041244
TI  - Comprehensive CO detection in flames using femtosecond two-photon laser-induced
      fluorescence.
AB  - We demonstrate a femtosecond two-photon laser-induced fluorescence (fs-TPLIF)
      technique for sensitive CO detection, using a 230 nm pulse of 9 uJ and 45 fs. The
      advantages of fs-TPLIF in excitation of molecular species were analyzed. Spectra
      of CO fs-TPLIF were recorded in stable laminar flames spatially resolved across
      the flame front. A hot band (1, n) together with the conventional band (0, n) of
      the B->A transitions were observed in the burned zone and attributed to the
      broadband nature of the fs excitation. The CO fs-TPLIF signal recorded across the
      focal point of the excitation beam shows a relatively flat intensity distribution
      despite of the steep laser intensity variation, which is beneficial for CO
      imaging in contrast to nanosecond and picosecond TPLIF. This phenomenon can be
      explained by photoionization, which over the short pulse duration dominates the
      population depletion of the excited B state due to the high peak power, but only
      contributes in total a negligible X state depletion due to the low pulse energy.
      Single-shot CO fs-TPLIF images in methane/air flames were recorded by imaging the
      broadband fluorescence. The results indicate that fs-TPLIF is a promising tool
      for CO imaging in flames.

PMID- 29041245
TI  - Frequency-constrained robust principal component analysis: a sparse
      representation approach to segmentation of dynamic features in optical coherence
      tomography imaging.
AB  - Sparse representation theory is an exciting area of research with recent
      applications in medical imaging and detection, segmentation, and quantitative
      analysis of biological processes. We present a variant on the robust-principal
      component analysis (RPCA) algorithm, called frequency constrained RPCA (FC-RPCA),
      for selectively segmenting dynamic phenomena that exhibit spectra within a user
      defined range of frequencies. The algorithm lacks subjective parameter tuning and
      demonstrates robust segmentation in datasets containing multiple motion sources
      and high amplitude noise. When tested on 17 ex-vivo, time lapse optical coherence
      tomography (OCT) B-scans of human ciliated epithelium, segmentation accuracies
      ranged between 91-99% and consistently out-performed traditional RPCA.

PMID- 29041246
TI  - Quantum dot emission modulation using piezoelectric photonic crystal MEMS
      resonators.
AB  - Quantum dots (QDs) integration into photonic devices requires varied approaches
      to control and modulate their emission. We demonstrate voltage-tunable PC
      structures with integrated QDs over suspended piezoelectric aluminum nitride thin
      film resonators that modulate PC enhancement at MHz frequencies. When the
      piezoelectric device is actuated at its resonant mechanical frequency, the
      extracted QD emission direction is likewise modulated via the optical resonant
      frequency of the PC. Modulation uses nanometer-scale mechanical displacements,
      offering the potential for greater switching speed and improved mechanical
      robustness that is not subject to the effects of stiction with a scalable
      fabrication approach.

PMID- 29041247
TI  - Resonance coupling and polarization conversion in terahertz metasurfaces with
      twisted split-ring resonator pairs.
AB  - We investigate edge-coupling of twisted split-ring resonator (SRR) pairs in the
      terahertz (THz) frequency range. Using a simple coupled-resonator model we show
      that such a system exhibits resonance splitting and cross-polarization
      conversion. Numerical simulations and experimental measurements agree well with
      theoretical calculations, verifying the resonance splitting as a function of the
      coupling strength given by the SRR separation. We further show that a metal
      ground plane can be integrated to significantly enhance the resonance coupling,
      which enables the effective control of resonance splitting and the efficiency and
      bandwidth of the cross-polarization conversion. Our findings improve the
      fundamental understanding of metamaterials with a view of accomplishing
      metamaterial functionalities with enhanced performance, which is of great
      interest in realizing THz functional devices required in a variety of
      applications.

PMID- 29041248
TI  - Low coherence digital holography microscopy based on the Lorenz-Mie scattering
      model.
AB  - We demonstrate the use of low spatial and temporal coherence holography
      microscopy, based on the Lorenz-Mie model, using the standard tungsten-halogen
      lamp present in an inverted microscope. An optical model is put forward to
      incorporate the effect of spectral width and different incidence angles of the
      incident light determined by the aperture at the back focal plane of the
      condenser lens. The model is validated for 899 nm diameter polystyrene
      microspheres in glycerol, giving a resolution of 0.4% for the index of refraction
      and 2.2% for the diameter of the particles.

PMID- 29041249
TI  - Occlusion handling using angular spectrum convolution in fully analytical mesh
      based computer generated hologram.
AB  - Occlusion handling in computer-generated holography is of vast importance as it
      enhances depth information by presenting correct motion parallax of the 3D scene
      within the viewing angle. In this paper, we propose a computationally efficient
      occlusion handling technique based on a fully analytic mesh based computer
      generated holography. The proposed technique uses angular spectrum convolution
      that renders exact occlusion while preserving all other aspects of the fully
      analytic mesh based computer generated holography. The proposed method is
      computationally efficient as only a single convolution operation is required for
      each mesh without numerical propagation between the meshes. The proposed method
      is also exact as it performs the occlusion processing in the tilted mesh plane,
      being free from artifacts coming from orthographic spatial masking. The proposed
      method can be applied to the self and the mutual occlusions between the objects
      in the 3D scene. The computer simulated results show the feasibility of the
      proposed method.

PMID- 29041250
TI  - Tunable artificial microwave blackbodies based on metasurfaces.
AB  - Inspired by the classic hole-cavity blackbody model, we propose an open
      metasurface blackbody operating at microwave frequencies, whose unit cell is a
      dielectric resonator lying on an opaque metal plate. The resonator has a high
      temperature coefficient of dielectric constant, thus the blackbody can be
      thermally tunable. Furthermore, when the resonator is combined with ferrite, a
      magnetically tunable blackbody is also obtained. Absorption spectra of these two
      tunable blackbody unit cells are measured, and they agree very well with the
      simulated results. The proposed blackbodies offer a new opportunity for practical
      tunable microwave absorbers in applications.

PMID- 29041251
TI  - Continuous-wave and passively Q-switched cryogenic Yb:KLu(WO4)2 laser.
AB  - We study cryogenic laser operation of an Yb-doped KLu(WO4)2 crystal pumped with a
      volume Bragg grating (VBG) stabilized diode laser at 981 nm. In the continuous
      wave laser regime, a maximum output power of 4.31 W is achieved at 80 K with a
      slope efficiency of 44.0% with respect to the incident pump power. Using a 85%
      initial transmission Cr:YAG crystal for passive Q-switching, an average output
      power of 2.11 W is achieved at 100 K for a repetition rate of 19 kHz. The pulse
      energy, pulse duration and peak power amount to 111 uJ, 231 ns and 0.48 kW,
      respectively.

PMID- 29041252
TI  - Large-format platinum silicide microwave kinetic inductance detectors for optical
      to near-IR astronomy.
AB  - We have fabricated and characterized 10,000 and 20,440 pixel Microwave Kinetic
      Inductance Detector (MKID) arrays for the Dark-speckle Near-IR Energy-resolved
      Superconducting Spectrophotometer (DARKNESS) and the MKID Exoplanet Camera (MEC).
      These instruments are designed to sit behind adaptive optics systems with the
      goal of directly imaging exoplanets in a 800-1400 nm band. Previous large optical
      and near-IR MKID arrays were fabricated using substoichiometric titanium nitride
      (TiN) on a silicon substrate. These arrays, however, suffered from severe non
      uniformities in the TiN critical temperature, causing resonances to shift away
      from their designed values and lowering usable detector yield. We have begun
      fabricating DARKNESS and MEC arrays using platinum silicide (PtSi) on sapphire
      instead of TiN. Not only do these arrays have much higher uniformity than the TiN
      arrays, resulting in higher pixel yields, they have demonstrated better spectral
      resolution than TiN MKIDs of similar design. PtSi MKIDs also do not display the
      hot pixel effects seen when illuminating TiN on silicon MKIDs with photons with
      wavelengths shorter than 1 um.

PMID- 29041253
TI  - Temperature-calibrated high-precision refractometer using a tilted fiber Bragg
      grating.
AB  - We present a refractometer with main- and vernier-scale to measure the refractive
      index (RI) of liquids with high precision by using the fine spectrum structure of
      a tilted fiber Bragg grating (TFBG). The absolute RI values are determined by the
      accurate wavelength of cut-off mode resonances. The main- and vernier-scale are
      calibrated by measuring large groups of fine spectra at different cut-off mode
      resonances in a small RI range, and the use of vernier-scale certainly reduces
      the RI measurement uncertainty resulted from the discrete cladding mode
      resonances. The performance of the TFBG-based vernier refractometer is
      experimentally verified by exploring the temperature dependence of RI of
      anhydrous ethanol in a near infrared region, showing an enhanced accuracy to the
      order of 10-4, high repeatability and temperature self-calibration capability.

PMID- 29041254
TI  - Mediated coupling of surface plasmon polaritons by a moving electron beam.
AB  - The mediated coupling of surface plasmon polaritons (SPPs) by a parallel moving
      electron beam is demonstrated in this paper. The theoretical analysis shows that
      the electron beam excited spoof surface plasmon polaritons (SSPs) on the grating
      placed above the metal films play the role as the excitation source in the
      mediated coupling. The numerical calculations and particle-in-cell simulations
      demonstrate the significant advantages of the SSPs mediately coupled SPPs in
      contrast with that coupled by the parallel moving electron beam directly. The
      photo density of the mediately coupled SPPs reaches up to 106 per cm2 for the
      electron beam with the charge density 100 nC/cm, which is two orders of magnitude
      larger than that of the directly coupled SPPs. The tuning band of the mediately
      coupled SPPs reaches up to 9% for the beam energy ranging from 10 keV to 30 keV,
      while it almost cannot be tuned for the direct coupling. The lifetime of the
      mediately coupled SPPs, which reaches up to hundreds of femtoseconds, is also
      much longer. Accordingly, the mediated coupling may bring great significances for
      the applications of SPPs.

PMID- 29041255
TI  - Effect of the gold crystallinity on the enhanced luminescence signal of scanning
      probe tips in apertureless near-field optical microscopy.
AB  - The effect of gold tip crystallinity on their spectral amplification
      characteristics, monitored through the luminescence enhanced by surface plasmon
      resonance (SPR), is investigated experimentally. As the tip radius increases, the
      grains composing polycrystalline tips become larger, resulting in a blueshift of
      the emission while a redshift of the SPR was predicted for monocrystalline gold.
      This reveals that the effect of the grain size, a parameter that has not been
      considered so far, is dominant over that of the tip radius. This study is
      significant to apertureless scanning near-field optical microscopy, where the
      gold tip emission defines the spectral antenna range.

PMID- 29041256
TI  - Polaritonic figure of merit of plane structures.
AB  - Based on the ability of plane structures to simultaneously optimize the
      propagation, confinement, and energy of surface plasmon-polaritons or surface
      phonon-polaritons, we develop the polaritonic figure of merit Z =
      betaRLambda2/delta, where betaR, Lambda and delta are the longitudinal wave
      vector, propagation length, and penetration depth, respectively. Explicit and
      analytical expressions of Z are derived for a single interface and a suspended
      thin film, as functions of the material permittivities and the film thickness.
      Higher Z are obtained for thinner films and smaller energy losses. The
      application of the obtained results for a SiC-air interface and a SiC thin film
      suspended in air shows that both structures are able to maximize the presence of
      polaritons at a frequency near to, but different than that at which the real part
      of the SiC permittivity exhibits a dip. Furthermore, using the temperature change
      of this dip, we show that the propagation length, confinement and energy of
      polaritons increases with its deepness, which provides an effective way to
      enhance the overall Z of polaritonic structures.

PMID- 29041257
TI  - Giant optical nonlinearity in DNA lyotropic liquid crystals.
AB  - We report the experimental evidence of nonlinear optical response in DNA
      lyotropic nematic liquid crystals. Pump-probe experiments indicate that the non
      linearity is remarkably large. Quantitative assessment of the non-linear optical
      coefficient by transient optical grating demonstrates that the response is of the
      same order of the well-known Giant Optical Nonlinearity (GON) of thermotropic
      nematics. These results represent a further incentive to the current
      investigation of potential applications of DNA in biophotonics.

PMID- 29041258
TI  - Manipulating refractive index, homogeneity and spectroscopy of Yb3+-doped silica
      core glass towards high-power large mode area photonic crystal fiber lasers.
AB  - Output power scaling of single mode large mode area (LMA) photonic crystal fiber
      (PCF) amplifiers urgently requires the low refractive index of Yb3+-doped silica
      glasses whilst maintaining high optical homogeneity. In this paper, we report on
      a promising alternative Yb3+/Al3+/F-/P5+-co-doped silica core-glass (YAFP), which
      is prepared by modified sol-gel method developed by our group and highly suitable
      for fabricating high power LMA PCF amplifiers. By controlling the doping
      combinations of Al3+/F-/P5+ in Yb3+-doped silica glass,it not only ensures low
      refractive index (RI) but also maintains the excellent optical homogeneity and
      spectroscopic properties of Yb3+. The spectroscopic properties of Yb3+ ions have
      not deteriorated by the co-doping of F- and P5+ in YAFP glass compared with that
      of Yb3+/Al3+ co-doped silica glass. A large-size (?5 mm * 90 mm) YAFP silica-core
      glass rod with low average RI difference of 2.6 * 10-4 (with respect to pure
      silica glass), and low radial and axial RI fluctuations of ~2 * 10-4, was
      prepared. A LMA PCF with 50 um core diameter was obtained by stack-capillary-draw
      techniques using YAFP core glass. Its core NA is 0.027. An average amplified
      power of 97 W peaking at 1030 nm and light-light efficiency of 54% are achieved
      from a 6.5 m long PCF in the pulse amplification laser experiment. Meanwhile,
      quasi-single-mode transmission is obtained with laser beam quality factor M2 of
      1.4.

PMID- 29041259
TI  - Non-reciprocal energy transport in linear and ring dynamic quantum networks and
      width-patterned optical waveguide arrays.
AB  - Non-reciprocal and uni-directional transport could efficiently transmit signals
      in integrated quantum and optical networks. It is shown that the time-dependent
      modulation of the position of quantum nodes would efficiently and non
      reciprocally guide an initially injected quantum energy. Moreover, the initial
      energy could be trapped within a ring configuration of such dynamically
      controlled quantum nodes. It is also shown that parallel waveguide arrays with
      specific widths pattern could uni-directly transfer a Gaussian beam across the
      arrays. By arranging the parallel waveguides on a cylindrical shell with a new
      widths pattern, the chiral transport of an incident Gaussian beam is also
      achieved.

PMID- 29041260
TI  - Compact acousto-optic imaging spectro-polarimeter for mineralogical
      investigations in the near infrared.
AB  - Spectral imaging in the near infrared is a promising method for mineralogy
      analysis, in particular well-suited for airless celestial objects or those with
      faint atmospheres. Additional information about structure and composition of
      minerals can be obtained using spectral polarimetry with high spatial resolution.
      We report design and performance of laboratory prototype for a compact near
      infrared acousto-optic imaging spectro-polarimeter, which may be implemented for
      remote or close-up analysis of planetary surfaces. The prototype features
      telecentric optics, apochromatic design over the bandwidth of 0.8-1.75 um, and
      simultaneous imaging of two orthogonal linear polarizations of the same scene
      with a single FPA detector. When validating the scheme, reflectance spectra of
      several minerals were measured with the spectral resolution of 100 cm-1 (10 nm
      passband at 1 um). When imaging samples, the spatial resolution of 0.6 mm at the
      target distance of one meter was reached. It corresponds to 100 by 100
      diffraction-limited elements resolved at the focal plane array (FPA) for each of
      the two light polarizations. A similar prototype is also being designed for the
      spectral range from 1.7 to 3.5 um. This type of the spectro-polarimeter is
      considered as a potential reconnaissance and analysis tool for future planetary
      or moon landers and rovers.

PMID- 29041261
TI  - Propagation analysis of phase-induced amplitude apodization optics based on
      boundary wave diffraction theory.
AB  - Phase-induced amplitude apodization (PIAA) is a promising technique in high
      contrast coronagraphs due to the characteristics of high efficiency and small
      inner working angle. In this letter, we present a new method for calculating the
      diffraction effects in PIAA coronagraphs based on boundary wave diffraction
      theory. We propose a numerical propagator in an azimuth boundary integral form,
      and then delve into its analytical propagator using stationary phase
      approximation. This propagator has straightforward physical meaning and obvious
      advantage on calculating efficiency, compared with former methods based on
      numerical integral or angular spectrum propagation method. Using this propagator,
      we can make a more direct explanation to the significant impact of pre-apodizer.
      This propagator can also be used to calculate the aberration propagation
      properties of PIAA optics. The calculating is also simplified since the
      decomposing procedure is not needed regardless of the form of the aberration.

PMID- 29041262
TI  - Nonlinear third harmonic generation at crystalline sapphires.
AB  - Third harmonic generation (THG) is a nonlinear optical phenomenon which can be
      applied in diverse research areas including interfacial studies, sub-wavelength
      light manipulation, and high sensitivity bio-molecular detection. Most precedent
      studies on THG have focused on dielectric and metallic materials, including
      silicon, gold, and germanium, due to their high nonlinear susceptibility.
      Sapphire, a widely-used optical substrate, has not been studied in depth for its
      third harmonic characteristics, despite its excellent optical transmission in the
      UV-visible range, high thermal conductance, and superior physical and chemical
      stability. In this research, we comprehensively studied THG at thin air
      dielectric interfaces of sapphire wafers by controlling the wafer cutting planes,
      focusing depth, incidence angle, laser intensity, and input polarization of the
      input laser beam. These findings can lead to broader use of third harmonics for
      high-precision sapphire characterization, such as surface quality inspection,
      crystallinity determination, interfacial studies, delamination check, and real
      time monitoring of crack propagation.

PMID- 29041263
TI  - Optimization of a waveguide-mode sensing chip for an ultraviolet near-field
      illumination biosensor.
AB  - A waveguide-mode sensor with a planar sensing chip, consisting of two waveguiding
      layers and a glass substrate, is a promising candidate for a near-field
      illumination biosensor. Aiming at using fluorescent labeling induced by
      ultraviolet light, we optimize the structure of a waveguide-mode sensing chip,
      based on the mechanism for enhancing ultraviolet near-field light revealed by
      numerical calculations. Candidates of optimal materials are also presented. The
      chip optimized as above should be able to enhance the intensity of ultraviolet
      near-field light 25 times as high as an Al surface plasmon resonance sensing
      chip.

PMID- 29041264
TI  - Stable CW laser based on low thermal expansion ceramic cavity with 4.9 mHz/s
      frequency drift.
AB  - We describe a CW laser stabilized to a low thermal expansion ceramic cavity which
      has a lower frequency drift rate than cavities based on ultralow-expansion glass
      (ULE), which are widely used as optical references. Two identical optical
      cavities with spacers of different material, ceramic and ULE, were assembled and
      the optical frequencies locked to each of these cavities were compared. The
      optical frequency drifts of both CW lasers were measured to within a precision of
      10-11 in one second over the course of one year. The ceramic cavity had a long
      term frequency drift rate of 4.9 mHz/s and the ULE cavity had one of 23 mHz/s.

PMID- 29041265
TI  - Common-signal-induced synchronization in photonic integrated circuits and its
      application to secure key distribution.
AB  - We experimentally achieve common-signal-induced synchronization in two photonic
      integrated circuits with short external cavities driven by a constant-amplitude
      random-phase light. The degree of synchronization can be controlled by changing
      the optical feedback phase of the two photonic integrated circuits. The change in
      the optical feedback phase leads to a significant redistribution of the spectral
      energy of optical and RF spectra, which is a unique characteristic of PICs with
      the short external cavity. The matching of the RF and optical spectra is
      necessary to achieve synchronization between the two PICs, and stable
      synchronization can be obtained over an hour in the presence of optical feedback.
      We succeed in generating information-theoretic secure keys and achieving the
      final key generation rate of 184 kb/s using the PICs.

PMID- 29041266
TI  - Toroidal resonance based optical modulator employing hybrid graphene-dielectric
      metasurface.
AB  - In this paper, we demonstrate the combination of a dielectric metasurface with a
      graphene layer to realize a high performance toroidal resonance based optical
      modulator. The dielectric metasurface consists of two mirrored asymmetric silicon
      split-ring resonators (ASSRRs) that can support strong toroidal dipolar resonance
      with narrow line width (~0.77 nm) and high quality (Q)-factor (~1702) and
      contrast ratio (~100%). Numerical simulation results show that the transmission
      amplitude of the toroidal dipolar resonance can be efficiently modulated by
      varying the Fermi energy EF when the graphene layer is integrated with the
      dielectric metasurface, and a max transmission coefficient difference up to 78%
      is achieved indicating that the proposed hybrid graphene/dielectric metasurface
      shows good performance as an optical modulator. The effects of the asymmetry
      degree of the ASSRRs on the toroidal dipolar resonance are studied and the
      efficiency of the transmission amplitude modulation of graphene is also
      investigated. Our results may also provide potential applications in optical
      filter and bio-chemical sensing.

PMID- 29041267
TI  - Propagation dynamics of partially coherent crescent-like optical beams in free
      space and turbulent atmosphere.
AB  - We introduce theoretically and realize experimentally a class of random, wide
      sense stationary optical beams with uniform correlations which, on propagation in
      free space, produce a crescent-like intensity distribution with the maximum at an
      off-axis position. The crescent's position of maximum intensity accelerates
      transversally at intermediate distances, and then exhibits a constant lateral
      shift further from the axis in the far zone of the source. We also show that on
      propagation in the isotropic turbulent atmosphere, the crescent beam shifts away
      from the axis as well, but slower than in free space, with rate depending on the
      strength of turbulence. These results are of importance for optical systems
      operating through long-range turbulent channels in which a beam must have a range
      dependent tilt, e.g. on travelling around an obstacle.

PMID- 29041268
TI  - Indistinguishable heralded single photon generation via relative temporal
      multiplexing of two sources.
AB  - Generating N single photons simultaneously is a formidable challenge due to the
      lack of deterministic single photon sources. Recent work [New J. Phys. 19, 063013
      (2017] has proposed a relative multiplexing scheme that can enhance the N single
      photons probability with a minimum of active switching resources. We
      experimentally demonstrate relative temporal multiplexing on two photon sources
      with a 90% additional enhancement over the standard temporal multiplexing scheme
      demonstrated previously. 88 +/- 11% visibility of Hong-Ou-Mandel quantum
      interference verifies the indistinguishability of the heralded single photons
      after the synchronization. This proof-of-principle demonstration points out the
      potential significance of the relative multiplexing scheme for large-scale
      photonic quantum information processing.

PMID- 29041269
TI  - Spectral anomalies and Gouy rotation around the singularity of ultrashort vortex
      pulses.
AB  - Spectral anomalies of femtosecond pulses with orbital angular momentum were
      studied in the vicinity of singularities. Bessel-Gauss (BG) beams were generated
      with mode-locked Ti:sapphire oscillators and dispersion-compensated diffractive
      axicons acting as spiral phase plates (SPPs). High-resolution two-dimensional
      spectral mapping was performed with a scanning fiber probe. Progressive rotation
      of the most pronounced features, known as "spectral eyes", in the maps of
      spectral moments was found at increasing propagation distance. The phenomenon is
      explained by a wavelength-dependent Gouy phase shift of interfering spectral
      components in the twisted wavefront. Spatial "spectral switching" was detected
      for few-cycle pulses. Possible improvements of selectivity are proposed.

PMID- 29041270
TI  - Quantitative dual-channel FRET microscopy.
AB  - Acceptor-sensitized quantitative Forster resonance energy transfer (FRET)
      measurement (E-FRET) is mainly impeded by donor emission crosstalk and acceptor
      direct excitation crosstalk. In this paper, we develop a novel E-FRET approach
      (Lux-E-FRET) based on linear unmixing (Lux) of the fluorescence intensity ratio
      between two detection channels with each excitation of two different wavelengths.
      The two detection channels need not to selectively collect the emission of donor
      or acceptor, and the excitation wavelengths need not to selectively excite donor
      or acceptor. For a tandem FRET sensor, Lux-E-FRET only needs single excitation
      wavelength. We performed Lux-E-FRET measurements on our dual-channel wide-field
      fluorescence microscope for FRET constructs in living cells, and obtained
      consistent FRET efficiencies with those measured by other methods. Collectively,
      Lux-E-FRET completely overcomes all spectral crosstalks and thus is applicable to
      the donor-acceptor pair with larger spectral overlapping.

PMID- 29041271
TI  - Three dimensional range geometry and texture data compression with space-filling
      curves.
AB  - This paper presents a novel method to effectively store three-dimensional (3D)
      data and 2D texture data into a regular 24-bit image. The proposed method uses
      the Hilbert space-filling curve to map the normalized unwrapped phase map to two
      8-bit color channels, and saves the third color channel for 2D texture storage.
      By further leveraging existing 2D image and video compression techniques, the
      proposed method can achieve high compression ratios while effectively preserving
      data quality. Since the encoding and decoding processes can be applied to most of
      the current 2D media platforms, this proposed compression method can make 3D data
      storage and transmission available for many electrical devices without requiring
      special hardware changes. Experiments demonstrate that if a lossless 2D
      image/video format is used, both original 3D geometry and 2D color texture can be
      accurately recovered; if lossy image/video compression is used, only black-and
      white or grayscale texture can be properly recovered, but much higher compression
      ratios (e.g., 1543:1 against the ASCII OBJ format) are achieved with slight loss
      of 3D geometry quality.

PMID- 29041272
TI  - Transition between bulk and surface refractive index sensitivity of micro-cavity
      in-line Mach-Zehnder interferometer induced by thin film deposition.
AB  - In this work we discuss the refractive index (RI) sensitivity of a micro-cavity
      in-line Mach-Zehnder interferometer in the form of a cylindrical hole (40-50 MUm
      in diameter) fabricated in a standard single-mode optical fiber using a
      femtosecond laser. The surface of the micro-cavity was coated with up to 400 nm
      aluminum oxide thin film using the atomic layer deposition method. Next, the film
      was progressively chemically etched and the influence on changes in the RI of
      liquid in the micro-cavity was determined at different stages of the experiment,
      i.e., at different thicknesses of the film. An effect of transition between
      sensitivity to the film thickness (surface) and the RI of liquid in the cavity
      (bulk) is demonstrated for the first time. We have found that depending on the
      interferometer working conditions determined by thin film properties, the device
      can be used for investigation of phenomena taking place at the surface, such as
      in case of specific label-free biosensing applications, or for small-volume RI
      analysis as required in analytical chemistry.

PMID- 29041273
TI  - Aperiodic nature of nanograting inscribed by femtosecond pulses.
AB  - A systematic study was performed, both experimentally and theoretically, to
      investigate the structural periodicity of nanogratings inscribed by focused
      femtosecond pulses on the surface of dielectrics. The results surprisingly show
      that although nanogratings generally appear periodic they are in fact
      intrinsically aperiodic. In the perpendicular writing scheme, the groove spacing
      gradually decreases from the middle part towards both sides. In the parallel
      writing scheme, the groove spacing varies quasiperiodically and the variation
      differs with respect to pulse-to-pulse spacing. Constant groove spacing was
      obtained only for a particular pulse-to-pulse spacing. These Gaussian-apodized
      and quasiperiodic variations are found to be intrinsic. They arise from the fact
      that the grooves are created, depending on the writing scheme, either by a series
      of local-lobes with different amplitudes and material feedbacks or by a repeated
      generated leading side-lobe with similar but not identical amplitudes and
      material feedbacks. The production of each single grooves result from a nonlinear
      and localized process from which arises its aperiodic nature. All these
      intrinsically Gaussian-apodized and quasiperiodic variations can be well
      interpreted based on the incubation-based nanoplasmonic model.

PMID- 29041274
TI  - Generalized shift-rotation absolute measurement method for high-numerical
      aperture spherical surfaces with global optimized wavefront reconstruction
      algorithm.
AB  - In this paper, a generalized shift-rotation absolute measurement method is
      proposed to measure the absolute surface shape of high-numerical-aperture
      spherical surfaces. Based on the wavefront difference method, the high order
      misalignment aberrations can be removed from the measurements. Our generalized
      shift-rotation absolute measurement process only needs one rotational measurement
      position and one translational measurement position. A wavefront reconstruction
      method based on the self-adaptive differential evolution algorithm is proposed to
      calculate the Zernike polynomials coefficient ai of the absolute surface shape
      Wtest(x,y), the rotation angle Deltatheta, the translation deltax along the x
      axis, and the translation deltay along the y axis. The translation error and
      rotation error in other absolute measurement methods are avoided using our
      generalized shift-rotation absolute measurement method. Experimental absolute
      results of the test surface and reference surface are given and the difference of
      reference surface shapes between two testings in experiments is 0.12 nm root mean
      square.

PMID- 29041275
TI  - Laser-induced erasable patterns in a N* liquid crystal on an iron doped lithium
      niobate surface.
AB  - A chiral nematic (N*) liquid crystal (LC) was hybridized with a z-cut iron doped
      lithium niobate (Fe:LN) substrate and exposed with a focused continuous wave
      diode laser beam. The N* LC layer was confined with a cover glass to provide a
      homogeneous LC layer thickness. Two distinct kinds of test cells were
      investigated, one with an uncoated glass covering slip and one with an indium tin
      oxide (ITO) coated cover glass. Photo generated electric fields (generated in the
      Fe:LN) resulted in a localized defect formation and textural transitions in the
      N* LC. Due to field confinement, the field induced responses were more localized
      in samples with ITO coated cover glasses. By scanning the laser beam on
      programmed trajectories, formation of persistent patterns could be achieved in
      the N* LC layer. Polarized optical microscopy of the exposed samples revealed
      that these patterns consisted of adjacent circular Frank-Pryce defects. Exposure
      with a slightly defocused laser beam could be applied selectively to erase these
      patterns. Thus, a promising method is reported to generate reconfigurable
      patterns, photonic motives, and touch sensitive devices in a hybridized N* LC
      with micron accuracy.

PMID- 29041276
TI  - High-resolution chalcogenide fiber bundles for longwave infrared imaging.
AB  - A flexible chalcogenide fiber bundle (FB) with a resolution as high as ~31 lp/mm
      has been fabricated for delivering thermal images of objects at room temperature.
      The FB is composed of ~200,000 single fibers with a Ge-As-Te-Se glass core 15 MUm
      in diameter and a polyetherimide (PEI) cladding 16.8 MUm in diameter. These Ge-As
      Te-Se/PEI fibers show good transparency in the 3-12 MUm spectral region. The
      fabricated FB presents a filling factor of ~72% and a crosstalk of ~1%. High
      quality thermal images of a human hand were obtained through the FB,
      demonstrating good potential of the FB for longwave infrared imaging in the areas
      such as medicine, industry and defense.

PMID- 29041277
TI  - 5.9 GHz graphene based q-switched modelocked mid-infrared monolithic waveguide
      laser.
AB  - A high repetition rate Q-switched modelocked ~2.1 um monolithic waveguide laser
      is reported. Ultrafast laser inscription is used to fabricate 3D depressed
      cladding channel waveguides in holmium doped yttrium aluminium garnet. This
      results in a transversely single mode waveguide laser. With the use of a graphene
      based saturable output coupler, Q-switched modelocking was achieved with a pulse
      repetition frequency of 5.9 GHz and up to 170 mW of average output power. This
      first demonstration of multi-GHz repetition rate operation from a Ho3+:YAG laser
      provides a compact and convenient source for a number of applications.

PMID- 29041278
TI  - Rapid optimization method of the strong stray light elimination for extremely
      weak light signal detection.
AB  - The strong stray light has huge interference on the detection of weak and small
      optical signals, and is difficult to suppress. In this paper, a miniaturized
      baffle with angled vanes was proposed and a rapid optimization model of strong
      light elimination was built, which has better suppression of the stray lights
      than the conventional vanes and can optimize the positions of the vanes
      efficiently and accurately. Furthermore, the light energy distribution model was
      built based on the light projection at a specific angle, and the light
      propagation models of the vanes and sidewalls were built based on the Lambert
      scattering, both of which act as the bias of a calculation method of stray light.
      Moreover, the Monte-Carlo method was employed to realize the Point Source
      Transmittance (PST) simulation, and the simulation result indicated that it was
      consistent with the calculation result based on our models, and the PST could be
      improved by 2-3 times at the small incident angles for the baffle designed by the
      new method. Meanwhile, the simulation result was verified by laboratory tests,
      and the new model with derived analytical expressions which can reduce the
      simulation time significantly.

PMID- 29041279
TI  - Bit-based support vector machine nonlinear detector for millimeter-wave radio
      over-fiber mobile fronthaul systems.
AB  - An effective bit-based support vector machine (SVM) is proposed as a non
      parameter nonlinear mitigation approach in the millimeter-wave radio-over-fiber
      (RoF) mobile fronthaul (MFH) system for various modulation formats. First, we
      analyze the impairments originated from nonlinearities in the millimeter-wave RoF
      system. Then we introduce the operation principle of the bit-based SVM detector.
      As a classifier, the SVM can create nonlinear decision boundaries by kernel
      function to mitigate the distortions caused by both linear and nonlinear noise.
      In our design, SVM can learn and capture the link characteristics from only a few
      training data without requiring the prior estimation of the system link. The bit
      based SVM only needs log2M SVMs to detect the signal of M-order modulation
      format. Experimental results have been obtained to verify the feasibility of the
      proposed method. The sensitivities are improved by 1.2-dB for 16-QAM, 1.3-dB for
      64-QAM, 1.8-dB for 16-APSK and 1.3-dB for 32-APSK at BER = 1E-3 with SVM
      detector, respectively. The proposed bit-based SVM gains a large improvement in
      the nonlinear system tolerance and outperforms the system employing k-means
      algorithm.

PMID- 29041280
TI  - On the substrate contribution to the back action trapping of plasmonic
      nanoparticles on resonant near-field traps in plasmonic films.
AB  - Nanoparticles trapped on resonant near-field apertures/engravings carved in
      plasmonic films experience optical forces due to the steep intensity gradient
      field of the aperture/engraving as well as the image like interaction with the
      substrate. For non-resonant nanoparticles the contribution of the substrate
      interaction to the trapping force in the vicinity of the trap
      (aperture/engraving) mode is negligible. But, in the case of plasmonic
      nanoparticles, the contribution of the substrate interaction to the low frequency
      stable trapping mode of the coupled particle-trap system increases as their
      resonance is tuned to the trap resonance. The strength of the substrate
      interaction depends on the height of the nanoparticle above the substrate. As a
      result, a difference in back action mechanism arises for nanoparticle
      displacements perpendicular to the substrate and along it. For nanoparticle
      displacements perpendicular to the substrate, the self induced back action
      component of the trap force arises due to changing interaction with the substrate
      as well as the trap. On the other hand, for displacements along the substrate, it
      arises solely due to the changing interaction with the trap. This additional
      contribution of the substrate leads to more pronounced back action. Numerical
      simulation results are presented to illustrate these effects using a bowtie
      engraving as the near-field trap and a nanorod as the trapped plasmonic
      nanoparticle. The substrate's role may be important in manipulation of plasmonic
      nanoparticles between successive traps of on-chip optical conveyor belts, because
      they have to traverse over regions of bare substrate while being handed off
      between these traps.

PMID- 29041281
TI  - Inhibited coupling guiding hollow fibers for label-free DNA detection.
AB  - The potentialities in using hollow core tube lattice fibers based on inhibited
      coupling wave-guiding for label-free DNA detection are numerically investigated
      and discussed here. The proposed sensing approach does not require any additional
      transducer component such as Bragg gratings, amplifying techniques such as
      nanoparticles nor coherent sources. It simply consists of the measurement of the
      transmittance of a piece of fiber some ten centimeters long. In case of matching
      DNA sequence, an additional bio-layer is laid down the dielectric-air interface
      causing a red shift of the transmission spectrum of the fiber. Results show a
      spectral sensitivity on the bio-layer with shift as high as 42 nm for every 10 nm
      of bio-layer and robustness against imperfect fiber coupling. The proposed
      approach can be easily applied to sensing of other complex molecular structures
      where the presence/absence of analyte can generate or not an additional layer.

PMID- 29041282
TI  - Dynamically tunable plasmon induced absorption in graphene-assisted
      metallodielectric grating.
AB  - The dynamically tunable plasmon induced absorption (PIA) effect is demonstrated
      in a graphene-assisted metallodielectric grating structure. Two methods are
      employed to achieve the tunable PIA effect in the mid-infrared region: one is
      based on controlling the chemical potential of graphene by adjusting the gate
      voltage, the other is related to varying the refractive index of interlayer. Our
      calculated results reveal that high tunability in amplitude and bandwidth of the
      PIA effect can be achieved by using the above-mentioned methods. Compared with
      previous results, our scheme is much easier to fabricate and has significant
      applications in modulators, absorbers and sensors.

PMID- 29041283
TI  - Self-generation of optical frequency comb in single section quantum dot Fabry
      Perot lasers: a theoretical study.
AB  - Optical Frequency Comb (OFC) generated by semiconductor lasers are currently
      widely used in the extremely timely field of high capacity optical interconnects
      and high precision spectroscopy. In the last decade, several experimental
      evidences of spontaneous OFC generation have been reported in single section
      Quantum Dot (QD) lasers. Here we provide a physical understanding of these self
      organization phenomena by simulating the multi-mode dynamics of a single section
      Fabry-Perot (FP) QD laser using a Time-Domain Traveling-Wave (TDTW) model that
      properly accounts for coherent radiation-matter interaction in the semiconductor
      active medium and includes the carrier grating generated by the optical standing
      wave pattern in the laser cavity. We show that the latter is the fundamental
      physical effect at the origin of the multi-mode spectrum appearing just above
      threshold. A self-mode-locking regime associated with the emission of OFC is
      achieved for higher bias currents and ascribed to nonlinear phase sensitive
      effects as Four Wave Mixing (FWM). Our results explain in detail the behaviour
      observed experimentally by different research groups and in different QD and
      Quantum Dash (QDash) devices.

PMID- 29041284
TI  - Single-shot dual-wavelength off-axis quasi-common-path digital holography using
      polarization-multiplexing.
AB  - We present a dual-wavelength off-axis quasi-common-path digital holography for
      quantitative phase imaging using polarization-multiplexing in a single shot.
      Employing an off-axis nearly common-path configuration, our approach separates
      the two-wavelength information using a polarizing beam splitter, while modulates
      the orthogonal fringe directions for each wavelength using two retro-reflector
      mirrors, and thus generates a single multiplexed off-axis interferogram on a
      monochrome CCD camera. The information of a specimen, including phase and height,
      is reconstructed through a division algorithm for dual wavelengths with the help
      of a specimen-free multiplexed interferogram. The experimental results obtained
      on a square step target and a circular step target illustrate the validity and
      stability of our setup.

PMID- 29041285
TI  - General noise suppression scheme with reference detection in heterodyne nonlinear
      spectroscopy.
AB  - We devised a novel two-step reference scheme that can greatly suppress the
      additive and convolutional noises in heterodyne nonlinear spectroscopy. To
      optimally remove additive noise, we fully utilized the spectral correlation in
      multi-channel reference data through a linear combination and regression
      algorithm. Using our pump-probe 2D IR spectrometer, we demonstrated that our
      scheme can improve the signal-to-noise ratio by 10-30 times and reach the noise
      floor of the signal detector. The new algorithm is guaranteed to reduce noise,
      enables the use of unmatched reference detectors, and does not introduce baseline
      shift or signal distortion. This scheme is applicable to many heterodyne
      spectroscopic techniques.

PMID- 29041286
TI  - Combination of additive and subtractive laser 3D microprocessing in hybrid
      glass/polymer microsystems for chemical sensing applications.
AB  - We present a novel hybrid glass-polymer micromechanical sensor by combining two
      femtosecond laser direct writing processes: laser illumination followed by
      chemical etching of glass and two-photon polymerization. This incorporation of
      techniques demonstrates the capability of combining mechanical deformable devices
      made of silica with an integrated polymer structure for passive chemical sensing
      application. We demonstrate that such a sensor could be utilized for
      investigating the elastic properties of polymeric microstructures fabricated via
      the two-photon polymerization technique. Moreover, we show that polymeric
      microstructure stiffness increases when immersed in organic liquids.

PMID- 29041287
TI  - High peak power ultrafast Yb:CaF2 oscillator pumped by a single-mode fiber
      coupled laser diode.
AB  - We demonstrate a high peak power mode-locked Yb:CaF2 oscillator pumped by a
      single-mode laser diode. The laser operated in hybrid Kerr-lens and SESAM mode
      locked regime. Its performance was optimized by varying the output coupler ratio.
      Pulses as short as 65 fs were generated with 0.4% transmission. Employing 5%
      output coupler enabled generation of 77 fs pulses with 46 kW of peak power (262
      mW of average output power). We believe that such high peak powers can open a way
      to practical applications of single-mode diode-pumped ultrafast ytterbium lasers.

PMID- 29041288
TI  - Reconstructing the surface of transparent objects by polarized light
      measurements.
AB  - The paper presents a method aimed at accurately reconstructing transparent
      objects using the area source. The method called polarized light measurements
      (PLM) combines two reconstruction techniques: polarization analyses and light
      path triangulation. The originality of this study relies on the PLM method that
      enables to extract the radiometric cues and geometric cues simultaneously during
      the surface reconstruction. To validate performance, a series of the comparison
      experiments are developed on different objects for the diverse thickness,
      material and curvature radius of unit under test. The subsequent error analyses
      are applied to evaluate the method, and the error distribution can be well
      observed in the results. The PLM performs an efficient process and a higher
      accuracy compared with traditional reconstruction on transparent objects made by
      the polarization analyses and triangulation method used alone.

PMID- 29041289
TI  - Smith-Purcell radiation from periodic beams.
AB  - Smith-Purcell effect is well known as a source of monochromatic electromagnetic
      radiation. In this paper we present the generalized theory of Smith-Purcell
      radiation from periodic beams. The form-factors describing both coherent and
      incoherent regimes of radiation are calculated. The radiation characteristics are
      investigated in two practically important frequency ranges, THz and X-ray, for
      two modulation profiles, most frequently used in practice - a train of
      microbunches and a Gaussian-shaped one, characterized by sinusoidal modulation
      with an arbitrary modulation depth. On the base of the theory developed we show
      that a modulated electron beam consisting of a set of bunches makes it possible
      to improve significantly the spectral line monochromaticity of the light emitted,
      reaching values better than 1% for short gratings. We demonstrate as well that
      Smith-Purcell radiation can be used for non-destructive diagnostics of the depth
      of modulation for partially modulated beams. These findings not only open up a
      new way to manipulate the light emission using Smith-Purcell effect but also
      promise a profound impact for other radiation sources based on charged particle
      beams, such as undulator radiation in FELs, next-generation X-ray radiation
      source based on inverse Compton scattering, in a wide range from THz to X-rays.

PMID- 29041290
TI  - Cross-sectional particle measurement in the resonance domain on the substrate
      through scatterometry.
AB  - We developed a versatile method for three-dimensional shape measurement where a
      specific particle can be selected on the substrate and its cross-sectional shape
      and size can be measured. A non-contact fast measurement is possible for the
      particle in the resonance domain. We applied rigorous coupled-wave analysis to
      the particle and calculated the diffraction patterns, comparing the patterns with
      the experimental results to obtain the size and shape. The shape and position of
      the focusing spot on the scattering particle was controlled precisely. With this
      method, the category of the analyzable object is extended to more shapes, such as
      rectangles and triangles, in addition to a conventional ellipsoid.

PMID- 29041291
TI  - Optical thermal sensor based on cholesteric film refilled with mixture of toluene
      and ethanol.
AB  - We demonstrate an optical thermal sensor based on cholesteric film refilled with
      mixture of toluene and ethanol. The thermal response mechanism is mainly based on
      the thermal expansion effect induce by toluene, where the ethanol is used for
      refractive index adjustment to determine the initial refection band position of
      cholesteric film. The ethanol-toluene mixture was used to adjust the color
      tunability with the temperature in relation with the habits of people (blue as
      cold, green as safe and red as hot). A broad temperature range of 86  degrees C
      and highly sensitivity of 1.79 nm/  degrees C are achieved in proposed thermal
      sensor, where the reflective color red-shifts from blue to red when environmental
      temperature increases from -6  degrees C to 80  degrees C. This battery-free
      thermal sensor possesses features including simple fabrication, low-cost, and
      broad temperature sensing range, showing potential application in scientific
      research and industry.

PMID- 29041292
TI  - Silicon crystallinity control during laser direct microstructuring with bursts of
      picosecond pulses.
AB  - Laser ablation and modification using bursts of picosecond pulses and a tightly
      focused laser beam are used to manufacture structures in the bulk silicon. We
      demonstrate precise control of the surface crystallinity as well as the structure
      depth and topography of the processed areas, achieving homogeneous surface
      properties. The control is achieved with a combination of a well-defined pulse
      energy, systematic pulse positioning on the material, and the number of pulses in
      a burst. A custom designed fiber laser source is used to generate bursts of 1, 5,
      10, and 20 pulses at a pulse repetition rate of 40 MHz and burst repetition rate
      of 83.3 kHz allowing for a fast and stable processing of silicon. We show a
      controlled transition through different laser-matter interaction regimes, from no
      observable changes of the silicon at low pulse energies, through amorphization
      below the ablation threshold energy, to the ablation with either complete,
      partial or nonexistent amorphization. Single micrometer-sized areas of desired
      shape and crystallinity were defined on the silicon surface with submicron
      precision, offering a promising tool for applications in the field of optics.

PMID- 29041293
TI  - Improved self-referenced biosensing with emphasis on multiple-resonance nanorod
      sensors.
AB  - We present a novel approach to improve self-referenced sensing based on multiple
      resonance nanorod structures. The method employs the maximum likelihood
      estimation (MLE) alongside a linear response model (LM), relating the sensor
      response (shifts in resonance wavelengths) to the changes due to surface binding
      and bulk refractive index. We also provide a solution to avoid repetitive
      simulations, that have been previously needed to determine the adlayer thickness
      sensitivity when measuring biological samples of different refractive indices.
      The finite element method (FEM) was used to model the nanorod structure, and the
      nanoimprint lithography was employed to fabricate them. The standard deviation of
      the results based on the MLE method is lower than that associated with the LM
      results. The method can be applied to an extended number of resonances to achieve
      a higher accuracy and precision.

PMID- 29041294
TI  - Room temperature strong coupling in a semiconductor microcavity with embedded
      AlGaAs quantum wells designed for polariton lasing.
AB  - We report a systematic study of the temperature and excitation density behavior
      of an AlAs/AlGaAs, vertically emitting microcavity with embedded ternary
      Al0.20Ga0.80As/AlAs quantum wells in the strong coupling regime. Temperature
      dependent photoluminescence measurements of the bare quantum wells indicate a
      crossover from the type-II indirect to the type-I direct transition. The
      resulting mixing of quantum well and barrier ground states in the conduction band
      leads to an estimated exciton binding energy systematically exceeding 25 meV. The
      formation of exciton-polaritons is evidenced in our quantum well microcavity via
      reflection measurements with Rabi splittings ranging from (13.93 +/- 0.15) meV at
      low temperature (30 K) to (8.58 +/- 0.40) meV at room temperature (300 K).
      Furthermore, the feasibility of polariton laser operation is demonstrated under
      non-resonant optical excitation conditions at 20 K and emission around 1.835 eV.

PMID- 29041295
TI  - Resonance control of a silicon micro-ring resonator modulator under high-speed
      operation using the intrinsic defect-mediated photocurrent.
AB  - A method to stabilize the resonance wavelength of a depletion-type silicon micro
      ring resonator modulator during high-speed operation is described. The method
      utilizes the intrinsic defect-mediated photo-absorption of a silicon waveguide
      and results in a modulator chip fabrication process that is free of heterogeneous
      integration (for example using germanium), thus significantly reducing the
      complexity and cost of manufacture. Residual defects, present after p-n junction
      formation, are found to produce an adequate photocurrent for use as a feedback
      signal, while an integrated heater is used to compensate for thermal drift via
      closed-loop control. The photocurrent is measured by a source-meter, which
      simultaneously provides a DC bias to the integrated heater during high-speed
      operation. A drop-port or an integrated extrinsic detector is not needed. This
      feedback control method is experimentally demonstrated via a computer-aided
      proportional-integral-differential loop. The resonance locking is validated for
      12.5 Gb/s intensity modulation in a back-to-back bit-error-rate measurement. The
      stabilization method described is not limited to a specific modulator design and
      is compatible with speeds greatly in excess of 12.5 Gb/s, in contrast to the
      bandwidth limitation of other stabilization methods that rely on intrinsic photo
      carrier generation through non-linear processes such as two-photon-absorption.
      Further, the use of intrinsic defects present after standard fabrication insures
      that no excess loss is associated with this stabilization method.

PMID- 29041296
TI  - Experimental demonstration of an intelligent control plane with proactive
      spectrum defragmentation in SD-EONs.
AB  - The cooperation of software-defined networking and flexible grid optical
      transport technology allows operators to elastically control the network using
      software running on a network operating system within a centralized way. However,
      existing approaches dealing with spectrum fragmentation are mostly the reactive
      strategy, which reconfigures network resources to overcome spectrum fragmentation
      when the controller detects the fragmentation. In this paper, we focus on how to
      improve the control plane intelligence of software-defined elastic optical
      networks (SD-EONs) by using a proactive strategy. More specifically, we design a
      novel routing, modulation level and spectrum allocation algorithm (RMLSA) based
      on spectral efficiency and connectivity (SEC) i.e., SEC-RMLSA, in order to
      improve the utilization efficiency of network resources. Meanwhile, we develop a
      routing application and an extended OpenFlow protocol to achieve a seamless
      operation between the controller and the optical data plane. Moreover, all the
      proposed methodologies are implemented and demonstrated in an SD-EON testbed that
      has both OpenFlow-based control plane and data plane. Finally, the proposed
      framework, experimental demonstration, and numerical evaluation are reported for
      different optical flows. The results show the system's overall feasibility and
      efficiency.

PMID- 29041297
TI  - Spin Hall effect of reflected light in dielectric magneto-optical thin film with
      a double-negative metamaterial substrate: erratum.
AB  - An expression error was produced in the text introducing the dynamic matrix of
      the magnetic layer in [Opt. Express25(16), 19117 (2017)10.1364/OE.25.019117].
      What's more, we used two wrong formula numbers in the analysis section of Eq.
      (11) and Eq. (13). Here we correct the errors.

PMID- 29041298
TI  - "W-shaped" injection current dependence of electroluminescence linewidth in green
      InGaN/GaN-based LED grown on silicon substrate.
AB  - Injection current, and temperature, dependences of the electroluminescence (EL)
      spectrum from green InGaN/GaN multiple quantum well (MQW)-based light-emitting
      diodes (LED) grown on a Si substrate, are investigated over a wide range of
      injection currents (0.5 uA-350 mA) and temperatures (6-350 K). The results show
      that an increasing temperature can result in the change of injection current
      dependent behavior of the EL spectrum in initial current range. That is, with
      increasing the injection current in the low current range, the emission process
      of the MQWs is dominated by filling effect of low-energetic localized states at
      the low temperature range of around 6 K, and by Coulomb screening of the quantum
      confinement Stark effect followed by a filling effect of the higher levels of the
      low-energetic localized states at the intermediate temperature range of around
      160 K. However, when the temperature is further raised to the higher temperature
      range of around 350 K, the emission process of the MQWs in the low current range
      is dominated by carrier-scattering effect followed by non-radiative recombination
      process. The aforementioned current-dependent behaviors of the EL spectrum are
      mainly attributed to the strong localized effect of the green LED, as confirmed
      by the anomalous temperature dependence of the EL spectrum measured at the low
      injection current of 5 uA. In addition, the injection current dependence of
      external quantum efficiency at different temperatures shows that, with increasing
      temperature from 6 to 350 K, in addition to the enhanced non-radiative
      recombination, electron overflow becomes more significant, especially in the
      higher temperature range above 300 K.

PMID- 29041299
TI  - Thermophotovoltaics with spectral and angular selective doped-oxide thermal
      emitters.
AB  - Deliberate control of thermal emission properties using nanophotonics has
      improved a number of applications including thermophotovoltaics (TPV), radiative
      cooling and infrared spectroscopy. In this work, we study the effect of
      simultaneous control of angular and spectral properties of thermal emitters on
      the efficiencies of TPV systems. While spectral selectivity reduces sub-bandgap
      losses, angular selectivity is expected to enhance view factors at larger
      separation distances and hence to provide flexibilities in cooling the
      photovoltaic converter. We propose a design of an angular and spectral selective
      thermal emitter based on waveguide perfect absorption phenomena in epsilon-near
      zero thin-films. Aluminum-doped Zinc-Oxide is used as an epsilon-near-zero
      material with a cross-over frequency in the near-infrared. A high contrast
      grating is designed to restrict the emission in a range of angles around the
      normal direction, while an integrated filter ensures spectral selectivity to
      reduce sub-bandgap losses. Theoretical analysis shows an expected relative
      enhancement of the TPV system efficiency of at least 32% using selective emitters
      with ideal angular and spectral selectivity at large separation distances
      compared to a blackbody. This enhancement factor, however, reduces to 3.9% with
      non-ideal selective emitters. This big reduction of the efficiency is attributed
      to sub-bandgap losses, off-angular losses and high-temperature dependence of
      optical constants.

PMID- 29041300
TI  - Comparison and application of wavelet transform and Kalman filtering for
      denoising in delta13CO2 measurement by tunable diode laser absorption
      spectroscopy at 2.008 um.
AB  - We propose to use the wavelet transform and Kalman filter methods for processing
      noise in delta13CO2 measurement using laser absorption spectroscopy at 2.008 um
      and they have been shown to be useful tool for reducing the intrinsic noise of
      the optical system. Through the performance comparison and analysis of these two
      denoising techniques for the intrinsic noise reduction of optical system, it can
      be found that the Kalman filter is a more suitable approach for the extraction of
      gas isotope measurement signal from a contaminated signal.

PMID- 29041301
TI  - Analytical modeling of light transport in scattering materials with strong
      absorption.
AB  - We have investigated the transport of light through slabs that both scatter and
      strongly absorb, a situation that occurs in diverse application fields ranging
      from biomedical optics, powder technology, to solid-state lighting. In
      particular, we study the transport of light in the visible wavelength range
      between 420 and 700 nm through silicone plates filled with YAG:Ce3+ phosphor
      particles, that even re-emit absorbed light at different wavelengths. We measure
      the total transmission, the total reflection, and the ballistic transmission of
      light through these plates. We obtain average single particle properties namely
      the scattering cross-section sigmas, the absorption cross-section sigmaa, and the
      anisotropy factor u using an analytical approach, namely the P3 approximation to
      the radiative transfer equation. We verify the extracted transport parameters
      using Monte-Carlo simulations of the light transport. Our approach fully
      describes the light propagation in phosphor diffuser plates that are used in
      white LEDs and that reveal a strong absorption (L/la > 1) up to L/la = 4, where L
      is the slab thickness, la is the absorption mean free path. In contrast, the
      widely used diffusion theory fails to describe this parameter range. Our approach
      is a suitable analytical tool for industry, since it provides a fast yet accurate
      determination of key transport parameters, and since it introduces predictive
      power into the design process of white light emitting diodes.

PMID- 29041302
TI  - Biomimetic spiral grating for stable and highly efficient absorption in
      crystalline silicon thin-film solar cells.
AB  - By emulating the phyllotaxis structure of natural plants, which has an efficient
      and stable light capture capability, a two-dimensional spiral grating is
      introduced on the surface of crystalline silicon solar cells to obtain both
      efficient and stable light absorption. Using the rigorous coupled wave analysis
      method, the absorption performance on structural parameter variations of spiral
      gratings is investigated firstly. Owing to diffraction resonance and excellent
      superficies antireflection, the integrated absorption of the optimal spiral
      grating cell is raised by about 77 percent compared with the conventional slab
      cell. Moreover, though a 15 percent deviation of structural parameters from the
      optimal spiral grating is applied, only a 5 percent decrease of the absorption is
      observed. This reveals that the performance of the proposed grating would
      tolerate large structural variations. Furthermore, the angular and polarization
      dependence on the absorption of the optimized cell is studied. For average
      polarizations, a small decrease of only 11 percent from the maximum absorption is
      observed within an incident angle ranging from -70 to 70 degrees. The results
      show promising application potentials of the biomimetic spiral grating in the
      solar cell.

PMID- 29041303
TI  - Laser emission from flash ignition of Zr/Al nanoparticles.
AB  - We report the first laser emission from flash ignition of Zr/Al nanoparticles
      with the addition of strong oxidizer KClO4 using Nd: YAG as a laser medium. The
      mixture Zr/Al/Kp-45 (mass ratio = 33%Zr: 33%Al: 34%KClO4) has the highest
      brightness temperature Tb = 4615 K and the adiabatic flame temperature Tf = 4194
      K with the duration of 20 ms. At 1064 nm we measured a maximum output energy of
      702.5 mJ with the duration of nearly 10 ms by using only 100 mg mixture with an
      output coupler (transmission T = 10%). Further optimizing the concentration
      cavity and increasing the mixture content will yield much higher efficiency and
      output energy.

PMID- 29041304
TI  - Land surface temperature retrieval from AMSR-E passive microwave data.
AB  - The land surface temperature (LST) is a key parameter for energy balance,
      evapotranspiration and climate change. In this study, two new methods of LST
      retrieval from passive microwave data are developed: one is deriving LST only
      using single-channel dual-polarized data based on the relationship between the
      emissivity and microwave polarization difference index (MPDI) (denoted as Method
      1); the other one is deriving LST using the traditional multi-channel method with
      prior knowledge of the normalized difference vegetation index (NDVI) (denoted as
      Method 3). Taking Moderate Resolution Imaging Spectroradiometer (MODIS) LST
      products as the actual LSTs, the coefficients for these algorithms are
      determined. From the results for the year 2008, it is demonstrated that the root
      mean square errors (RMSEs) for the LST retrieval using Method 3 are the smallest
      and range from 2.92 K to 3.44 K, the RMSEs for the LST retrieval using
      traditional multi-channel method (denoted as Method 2) range from 3.07 K to 4.05
      K, and the worst results come from Method 1, whose RMSEs range from 3.11 K to
      4.13 K at a frequency of 89 GHz. This could be caused by the fact that the NDVI
      provides substantial emissivity knowledge in Method 3, and much richer vegetation
      could result in a more accurate emissivity estimation.

PMID- 29041305
TI  - Remote sensing of atmospheric NO2 by employing the continuous-wave differential
      absorption lidar technique.
AB  - Differential absorption lidar (DIAL) technique employed for remote sensing has
      been so far based on the sophisticated narrow-band pulsed laser sources, which
      require intensive maintenance during operation. In this work, a continuous-wave
      (CW) NO2 DIAL system based on the Scheimpflug principle has been developed by
      employing a compact high-power CW multimode 450 nm laser diode as the light
      source. Laser emissions at the on-line and off-line wavelengths of the NO2
      absorption spectrum are implemented by tuning the injection current of the laser
      diode. Lidar signals are detected by a 45 degrees  tilted area CCD image sensor
      satisfying the Scheimpflug principle. Range-resolved NO2 concentrations on a near
      horizontal path are obtained by the NO2 DIAL system in the range of 0.3-3 km and
      show good agreement with those measured by a conventional air pollution
      monitoring station. A detection sensitivity of +/- 0.9 ppbv at 95% confidence
      level in the region of 0.3-1 km is achieved with 15-minute averaging and 700 m
      range resolution during hours of darkness, which allows accurate concentration
      measurement of ambient NO2. The low-cost and robust DIAL system demonstrated in
      this work opens up many possibilities for field NO2 remote sensing applications.

PMID- 29041306
TI  - Mixed basis quantum key distribution with linear optics.
AB  - Two-qubit quantum codes have been suggested to obtain better efficiency and
      higher loss tolerance in quantum key distribution. Here, we propose a two-qubit
      quantum key distribution protocol based on a mixed basis consisting of two Bell
      states and two states from the computational basis. All states can be generated
      from a single entangled photon pair resource by using local operations on only
      one auxiliary photon. Compared to other schemes it is also possible to
      deterministically discriminate all states using linear optics. Additionally, our
      protocol can be implemented with today's technology. When discussing the security
      of our protocol we find a much improved resistance against certain attacks as
      compared to the standard BB84 protocol.

PMID- 29041307
TI  - Optical bistablility in six-wave mixing parametrical amplification.
AB  - We investigate the nonreciprocity "infinity"-shape optical bistability (OB)
      induced by the feedback dressing effect of six-wave mixing parametrically
      amplified process in a four-level atomic system. Compared to the traditional OB
      by scanning power, the "infinity"-shape OB is scanning probe frequency and
      demonstrated by "infinity"-shape non-overlapping region. More, this non
      overlapping region in the x direction (frequency difference) and in the y
      direction (intensity difference) could demonstrate the degree of this OB
      phenomenon of dressed probe and conjugate signals, which can be changed by the
      intensity of feedback dressing. Further, we find the feedback intensity can be
      controlled by experimental parameters include powers of external-dressing,
      frequency detuning, incident phase and the nonlinear phase shift of internal
      dressing beam. As a result, the nonreciprocity "infinity"-shape OB is more
      sensitive and multiple than traditional OB. These outcomes have potential
      applications in logic-gate devices and quantum information processing.

PMID- 29041308
TI  - Directional enhancement of selected high-order-harmonics from intense laser
      irradiated blazed grating targets.
AB  - Relativistically intense laser solid target interaction has been proved to be a
      promising way to generate high-order harmonics, which can be used to diagnose
      ultrafast phenomena. However, their emission direction and spectra still lack
      tunability. Based upon two-dimensional particle-in-cell simulations, we show that
      directional enhancement of selected high-order-harmonics can be realized using
      blazed grating targets. Such targets can select harmonics with frequencies being
      integer times of the grating frequency. Meanwhile, the radiation intensity and
      emission area of the harmonics are increased. The emission direction is
      controlled by tailoring the local blazed structure. Theoretical and electron
      dynamics analysis for harmonics generation, selection and directional enhancement
      from the interaction between multi-cycle laser and grating target are carried
      out. These studies will benefit the generation and application of laser plasma
      based high order harmonics.

PMID- 29041309
TI  - Tunable Goos-Hanchen shift from graphene ribbon array.
AB  - The Goos-Hanchen (GH) shift of light beam incident on graphene ribbon array is
      investigated by Green's function method. Due to the resonance effects of leaky
      surface plasmons on ribbons, the zeroth-order reflection field shows both giant
      positive and negative GH shifts. By tuning the graphene Fermi level, we can
      control the shift conveniently. This effect is important to graphene-based
      metasurface and electro-optical devices.

PMID- 29041310
TI  - Simultaneous Airy beam generation for both surface plasmon polaritons and
      transmitted wave based on metasurface.
AB  - Based on the amplitude and phase modulation of subwavelength slits, a metasurface
      which can simultaneously generate Airy beam for surface plasmon polaritons (SPPs)
      and transmitted wave is presented. Interestingly, by changing the handedness of
      circularly polarized light, the position of SPPs Airy beam can be switched to the
      left or right side of the metasurface, while the field distribution and the
      position of the Airy beam for transmitted wave are not affected. The
      nondiffracting, self-bending and self-healing properties of the generated Airy
      beams are analyzed as well. In addition, abruptly autofocusing of SPPs and
      transmitted wave are demonstrated by interfering two Airy beams. The dual
      functionality and chirality features of the metasurface can provide more freedoms
      in the potential applications of Airy beams.

PMID- 29041311
TI  - Metallic metasurfaces for high efficient polarization conversion control in
      transmission mode.
AB  - A high efficient broadband polarization converter is an important component in
      integrated miniaturized optical systems, but its performances is often restricted
      by the material structures, metallic metasurfaces for polarization control in
      transmission mode never achieved efficiency above 0.5. Herein, we theoretically
      demonstrate that metallic metasurfaces constructed by thick cross-shaped
      particles can realize a high efficient polarization transformation over a
      broadband. We investigated the resonant properties of designed matesurfaces and
      found that the interaction between double FP cavity resonances and double bulk
      magnetic resonances is the main reason to generate a high transmissivity over a
      broadband. In addition, through using four resonances effect and tuning the
      anisotropic optical response, we realized a high efficient (> 0.85) quarter-wave
      plate at the wavelength range from 1175nm to 1310nm and a high efficient (> 0.9)
      half-wave plate at the wavelength range from 1130nm to 1230nm. The proposed
      polarization converters may have many potential applications in integrated
      polarization conversion devices and optical data storage systems.

PMID- 29041312
TI  - Automatic spectral calibration for polarization-sensitive optical coherence
      tomography.
AB  - Accurate wavelength assignment is important for Fourier domain polarization
      sensitive optical coherence tomography. Incorrect wavelength mapping between the
      orthogonal horizontal (H) and vertical (V) polarization channels leads to
      broadening the axial point spread function and generating polarization artifacts.
      To solve the problem, we propose an automatic spectral calibration method by
      seeking the optimal calibration coefficient between wavenumber kH and kV. The
      method first performs a rough calibration to get the relationship between the
      wavelength lambda and the pixel number x of the CCD for each channel. And then a
      precise calibration is taken to bring both polarization interferograms in the
      same k range through the optimal calibration coefficient. The optimal coefficient
      is automatically obtained by evaluating the cross-correlation of A-line signals.
      Simulations and experiments are implemented to demonstrate the performance of the
      proposed method. The results show that, compared to the peaks method, the
      proposed method is suitable in both Gaussian and non-Gaussian spectrums with a
      higher calibration accuracy.

PMID- 29041313
TI  - Lasing in ring resonators by stimulated Brillouin scattering in the presence of
      nonlinear loss.
AB  - We theoretically investigate lasing due to stimulated Brillouin scattering in
      integrated ring resonators. We give analytic expressions and numerical
      calculations for the lasing threshold for rings in the presence of for both
      linear and nonlinear loss. We demonstrate the operation of the ring in the
      different regimes of amplification and lasing, and show how these regimes depend
      on the coupling to the ring and on the nonlinear parameters. In the case of
      nonlinear losses, we find that there can exist an upper threshold to the lasing
      regime where the losses are dominated by free-carrier absorption. We also find
      that nonlinear losses can inhibit Brillouin lasing entirely for certain ranges of
      coupling parameters, and we show how the correct ranges of coupling parameters
      can be calculated and optimized for the design of integrated Brillouin lasers.

PMID- 29041314
TI  - Photonic integration platform with pump free microfluidics.
AB  - Chip based particle sensing using 3D capillary fill microfluidics integrated with
      monolithically integrated lasers and photodetectors is used to demonstrate the
      feasibility of true chip scale photonic measurements of fluids. The approach is
      scalable and manufactured using industry standard compound semiconductor
      fabrication tools. The need for fluid speed regulation via external pumps is
      removed by measuring local particle velocity at the point of interrogation and
      particle position within the fluid flow is derived from multiple time resolved
      forward scattered light signals. Particle size discrimination of 10 and 15 MUm
      polystyrene microbeads is used as an example.

PMID- 29041315
TI  - Proposal and numerical study of a flexible visible photonic crystal defect cavity
      for nanoscale strain sensors.
AB  - A flexible photonic crystal cavity, consisting of a III-V active layer embedded
      in a flexible medium, with a line-defect by removing three air holes for
      nanoscale structural deformation detection is proposed and optimized. The cavity
      can hold the photonic band-gap modes with the fundamental mode located at
      approximately 686 nm, overlapping with the photoluminescence spectrum of the
      InGaP/InGaAlP quantum wells. Results of finite-difference time-domain simulations
      indicate that the L3 cavity features an ultra-compact mode volume of 10-3 um3 and
      high quality factor of 104 at a sub-micron footprint within the studied visible
      wavelength. Theoretical optical strain sensitivities of approximately 4.5 and 3
      nm per epsilon (1% strain for both) for the x and y directions are predicted,
      respectively. When the cavity is under large bending curvatures, the Q factor
      rapidly decreases from 8000 to 2000.

PMID- 29041316
TI  - Nonadiabatic redshifts in high-order harmonic generation from solids.
AB  - We studied the multi-plateau high-order harmonic generation (HHG) from solids
      numerically. It is found that the HHG spectra in the second and higher plateaus
      are redshifted in short laser pulses due to the nonadiabatic effect. The
      corresponding FWHMs also increase as a function of the harmonic order, suggesting
      the step-by-step excitation of higher conduction bands in the HHG process.
      Although the system is symmetric in the coordinate space, even-order harmonics
      are present. It is due to the fact that the symmetry of electron motions and the
      population in the higher conduction bands is broken in the k space and time
      domain based on the indirect step-by-step excitation model. Our numerical results
      are in good agreement with recent experimental measurements of Ndabashimiye et
      al. [Nature 534, 520 (2016)].

PMID- 29041317
TI  - Experimental demonstration of multi-cavity optoelectronic oscillation over a
      multicore fiber.
AB  - We report, for the first time to our knowledge, the experimental demonstration of
      multi-cavity optoelectronic oscillators where the cavities are provided by the
      different cores of a multicore fiber. We implemented two multi-cavity
      architectures over a 20-m-long 7-core fiber link: unbalanced dual-cavity
      oscillation (the cavity lengths are a multiple of a reference value) and multi
      cavity Vernier oscillation (the cavity lengths are slightly different). Since all
      the cavities are hosted under a single fiber cladding and are subject to the same
      environmental and mechanical conditions, optoelectronic oscillators built upon
      multicore fibers benefit from improved performance stability as compared to
      independent singlemode fiber cavities.

PMID- 29041318
TI  - Composite multiscale entropy analysis of reflective terahertz signals for
      biological tissues.
AB  - We demonstrate a composite multiscale entropy (CMSE) method of terahertz (THz)
      signal complexity analysis to distinguish different biological tissues. The THz
      signals reflected from fresh porcine skin and muscle tissues were measured and
      analyzed. The statistically significant difference and separation of the two
      tissues based on several parameters were analyzed and compared for THz
      spectroscopy and imaging, which verified the better performance of the CMSE
      method and further enhancement of the contrast among THz signals that interact
      with different tissues. This process provides a better analysis and
      discrimination method for THz spectroscopy and imaging in biomedical
      applications.

PMID- 29041319
TI  - 8 x 8 wavelength router of optical network on chip.
AB  - An integrated 8 x 8 wavelength router based on the micro-ring resonators using 2
      x 2 multi-interference (MMI) crossing is demonstrated on silicon-on-insulator
      (SOI) technology, which is manufactured with microelectronics equipment.
      Experimental results show a free spectral range (FSR) about ~37 nm, an on/off
      contrast larger than 20 dB, an imbalance among the channels less than 2 dB, a
      crosstalk of channels smaller than -10 dB, a spacing between close channels about
      3.6 +/- 0.7 nm and an output efficiency of every channel smaller than 20 dB.

PMID- 29041320
TI  - Fabrication of high-temperature tilted fiber Bragg gratings using a femtosecond
      laser.
AB  - We developed a new method to fabricate tilted fiber Bragg gratings (TFBGs) by
      using a femtosecond laser with a phase mask. During the laser processing, the
      fiber was obliquely moved at a tilt angle, in which the laser beam and the phase
      mask were fixed. The peak loss of the cladding modes with a tilt angle of 4.9
      degrees  reaches to ~-8 dB, and the insertion loss is less than -0.2 dB. The TFBG
      was stable at temperature up to 700 degrees C and slight degraded at 800  degrees
      C. The temperature sensing of the TFBG was demonstrated at a high temperature up
      to 800 degrees C. The temperature sensitivities of the Bragg mode, the ghost
      mode, and the cladding mode were measured to be 15.72 pm/ degrees C, 15.56 pm/
      degrees C, and 15.52 pm/ degrees C, respectively. The refractive index response
      of the TFBGs was also measured.

PMID- 29041321
TI  - Quantitative microfluidic delivery based on an optical breakdown-driven micro
      pump for the fabrication of fiber functional devices.
AB  - An optical breakdown-driven micro-pump was reported to deliver the quantitative
      liquid to the fiber microstructure efficiently. The amount of the pumped liquid
      can be controlled by adjusting the irradiation time of the femtosecond laser
      pulses. Such a method of microfluidic delivery has potential for the fabrication
      of fiber functional devices and the rapid injection of analytes into a lab-in
      fiber for chemical and biological analysis. As a demonstration, a fiber spirit
      level based on a mobile microbubble was achieved by pumping nanoliter scale
      liquid into a fiber micro-cavity with this method.

PMID- 29041322
TI  - Near-zero-index wires.
AB  - In this work, near-zero-index material boundary properties have been exploited to
      achieve new electromagnetic functionalities. The extraordinary guiding properties
      of a cylindrical dielectric rod waveguide surrounded by a thin epsilon-mu-near
      zero shell is analyzed and discussed. A closed-form solution for the dispersion
      equation has been developed, able to model and design such properties at will.
      Analytical and numerical results will confirm that the use of near-zero cover
      materials leads to extraordinary properties in terms of field configurations, low
      attenuation, and bandwidth. The dielectric wire acts as an efficient "waveguide"
      with great potentials for advance nanocircuit and electronics.

PMID- 29041323
TI  - Boundary element method for 2D materials and thin films.
AB  - 2D materials emerge as a viable platform for the control of light at the
      nanoscale. In this context the need has arisen for a fast and reliable tool
      capable of capturing their strictly 2D nature in 3D light scattering simulations.
      So far, 2D materials and their patterned structures (ribbons, discs, etc.) have
      been mostly treated as very thin films of subnanometer thickness with an
      effective dielectric function derived from their 2D optical conductivity. In this
      study an extension to the existing framework of the boundary element method (BEM)
      with 2D materials treated as a conductive interface between two media is
      presented. The testing of our enhanced method on problems with known analytical
      solutions reveals that for certain types of tasks the new modification is faster
      than the original BEM algorithm. Furthermore, the representation of 2D materials
      as an interface allows us to simulate problems in which their optical properties
      depend on spatial coordinates. Such spatial dependence can occur naturally or can
      be tailored artificially to attain new functional properties.

PMID- 29041324
TI  - Weyl points in a magnetic tetrahedral photonic crystal: erratum.
AB  - We present an erratum regarding the number of space group in our paper.

PMID- 29041325
TI  - Spatial mode multiplexing using volume holographic gratings.
AB  - We experimentally demonstrate spatial mode multiplexing of optical beams using
      multiplexed volume holographic gratings (MVGHs) formed in phenanthrenquinone-poly
      (methyl methacrylate) (PQ-PMMA) photopolymer. Multiple spatial modes of Laguerre
      Gaussian (LG) beams are recorded at the same pupil area of a volume hologram
      resulting in MVHGs, for simultaneous reconstruction of spatial modes. In
      addition, a helical phase beam, a non-diffracting beam with conical phase
      profile, and a parabolic non-diffracting beam with cubic phase profile have also
      been simultaneously recorded and reconstructed from MVHGs. Utilizing Bragg
      wavelength degeneracy property of volume hologram these multiplexed modes are
      reconstructed at multiple wavelengths ranging from blue (450nm) to red (635). Due
      to combined effect of three-dimensional pupil, Bragg wavelength degeneracy,
      angular selectivity, together with spatial mode properties these, MVHGs can act
      as spatial mode filter with spectral filtering property. Advantages of volume
      holography in beam shaping are discussed. Multiple first diffraction orders with
      desired beam shapes obtained from the single optical element (i.e. a volume
      hologram with MVHGs) may find important applications in optical communication
      experiments, and in volume holographic imaging and microscopy. Experimental
      results show solid evidence that MVGHs in beam shaping provide a simple, compact,
      single element, and direct way to multiplex spatial modes.

PMID- 29041326
TI  - Polarization imaging camera with a waveplate array fabricated with a femtosecond
      laser inside silica glass.
AB  - In this study, we demonstrate a polarization imaging camera with a waveplate
      array of a silica glass fabricated by femtosecond (fs) laser direct writing. To
      use a waveplate array of silica glass for polarization imaging, non-uniformity of
      the transmittance and retardance in the waveplates must be considered. Therefore,
      we used a general method of polarization analysis with system matrices determined
      experimentally for all the units in the waveplate array. We found that a figure
      of merit based on the determinant of the system matrix could be applied to
      improve the accuracy of analysis and the robustness to the retardance dispersion
      for both the simulated and the fabricated waveplate array.

PMID- 29041327
TI  - Tunable optical switching in the near-infrared spectral regime by employing
      plasmonic nanoantennas containing phase change materials.
AB  - We propose the design of switchable plasmonic nanoantennas (SPNs) that can be
      employed for optical switching in the near-infrared regime. The proposed SPNs
      consist of nanoantenna structures made up of a plasmonic metal (gold) such that
      these nanoantennas are filled with a switchable material (vanadium dioxide). We
      compare the results of these SPNs with inverted SPN structures that consist of
      gold nanoantenna structures surrounded by a layer of vanadium dioxide (VO2) on
      their outer surface. These nanoantennas demonstrate switching of electric-field
      intensity enhancement (EFIE) between two states (On and Off states), which can be
      induced thermally, optically or electrically. The On and Off states of the
      nanoantennas correspond to the metallic and semiconductor states, respectively of
      the VO2 film inside or around the nanoantennas, as the VO2 film exhibits phase
      transition from its semiconductor state to the metallic state upon application of
      thermal, optical, or electrical energy. We employ finite-difference time-domain
      (FDTD) simulations to demonstrate switching in the EFIE for four different SPN
      geometries - nanorod-dipole, bowtie, planar trapezoidal toothed log-periodic, and
      rod-disk - and compare their near-field distributions for the On and Off states
      of the SPNs. We also demonstrate that the resonance wavelength of the EFIE
      spectra gets substantially modified when these SPNs switch between the two
      states.

PMID- 29041328
TI  - Dual polarization split lenses.
AB  - We report the realization of polarization sensitive split lens configurations.
      While split lenses can be used to easily generate different types of controlled
      structured light patterns, their realization has been limited so far to scalar
      beams. Here we propose and experimentally demonstrate their generalization to
      vectorial split lenses, leading to light patterns with customized intensity and
      state of polarization. We demonstrate how these polarization split lenses can be
      experimentally implemented by means of an optical system using two liquid crystal
      spatial light modulators, each one phase modulating one orthogonal polarization
      component. As a result, we demonstrate the experimental generation of vectorial
      beams with different shapes generated with these dual polarization split lenses.
      Excellent experimental results are provided in each case. The proposed technique
      is a simple method to generate structured light beams with polarization
      diversity, with potential applications in polarimetry, customized illuminators or
      quantum optics.

PMID- 29041329
TI  - Silicon-organic hybrid (SOH) modulators for intensity-modulation / direct
      detection links with line rates of up to 120 Gbit/s.
AB  - High-speed interconnects in data-center and campus-area networks crucially rely
      on efficient and technically simple transmission techniques that use intensity
      modulation and direct detection (IM/DD) to bridge distances of up to a few
      kilometers. This requires electro-optic modulators that combine low operation
      voltages with large modulation bandwidth and that can be operated at high symbol
      rates using integrated drive circuits. Here we explore the potential of silicon
      organic hybrid (SOH) Mach-Zehnder modulators (MZM) for generating high-speed
      IM/DD signals at line rates of up to 120 Gbit/s. Using a SiGe BiCMOS signal
      conditioning chip, we demonstrate that intensity-modulated duobinary (IDB)
      signaling allows to efficiently use the electrical bandwidth, thereby enabling
      line rates of up to 100 Gbit/s at bit error ratios (BER) of 8.5 * 10-5. This is
      the highest data rate achieved so far using a silicon-based MZM in combination
      with a dedicated signal-conditioning integrated circuit (IC). We further show
      four-level pulse-amplitude modulation (PAM4) at lines rates of up to 120 Gbit/s
      (BER = 3.2 * 10-3) using a high-speed arbitrary-waveform generator and a 0.5 mm
      long MZM. This is the highest data rate hitherto achieved with a sub-millimeter
      MZM on the silicon photonic platform.

PMID- 29041330
TI  - Electrically tunable binary phase Fresnel lens based on a dielectric elastomer
      actuator.
AB  - We propose and demonstrate an all-solid-state tunable binary phase Fresnel lens
      with electrically controllable focal length. The lens is composed of a binary
      phase Fresnel zone plate, a circular acrylic frame, and a dielectric elastomer
      (DE) actuator which is made of a thin DE layer and two compliant electrodes using
      silver nanowires. Under electric potential, the actuator produces in-plane
      deformation in a radial direction that can compress the Fresnel zones. The
      electrically-induced deformation compresses the Fresnel zones to be contracted as
      high as 9.1% and changes the focal length, getting shorter from 20.0 cm to 14.5
      cm. The measured change in the focal length of the fabricated lens is consistent
      with the result estimated from numerical simulation.

PMID- 29041331
TI  - Chromatic aberrations correction for imaging spectrometer based on acousto-optic
      tunable filter with two transducers.
AB  - The acousto-optic tunable filter (AOTF) with wide wavelength range and high
      spectral resolution has long crystal and two transducers. A longer crystal length
      leads to a bigger chromatic focal shift and the double-transducer arrangement
      induces angular mutation in diffracted beam, which increase difficulty in
      longitudinal and lateral chromatic aberration correction respectively. In this
      study, the two chromatic aberrations are analyzed quantitatively based on an AOTF
      optical model and a novel catadioptric dual-path configuration is proposed to
      correct both the chromatic aberrations. The test results exhibit effectiveness of
      the optical configuration for this type of AOTF-based imaging spectrometer.

PMID- 29041332
TI  - Rabi oscillations in the spatial profiles of superfluorescent pulses from
      rubidium vapor.
AB  - In this study, we investigate 420-nm yoked superfluorescence (YSF) emitted from
      the atomic vapor of rubidium (Rb) by driving the Rb 5S - 5D two-photon transition
      with an ultrashort pulsed laser. When the pump pulse is close to its transform
      limit (~ 100 fs) or down-chirped up to around 200 fs, the 420-nm YSF appears as a
      low-divergence beam with a ring-shaped radial profile. Although such a beam
      profile is less sensitive to the vapor pressure of Rb in a cell, its diameter
      rigorously varies as a function of the pump-pulse power. By numerically solving a
      time-dependent Schrodinger equation for a single-Rb atom, we well reproduce our
      experimental observation, indicating that a single-atom Rabi oscillation is
      responsible for the spatial beam profile of the 420-nm emission.

PMID- 29041333
TI  - Coded aperture optimization in compressive X-ray tomography: a gradient descent
      approach.
AB  - Coded aperture X-ray computed tomography (CT) has the potential to revolutionize
      X-ray tomography systems in medical imaging and air and rail transit security -
      both areas of global importance. It allows either a reduced set of measurements
      in X-ray CT without degradation in image reconstruction, or measure multiplexed X
      rays to simplify the sensing geometry. Measurement reduction is of particular
      interest in medical imaging to reduce radiation, and airport security often
      imposes practical constraints leading to limited angle geometries. Coded aperture
      compressive X-ray CT places a coded aperture pattern in front of the X-ray source
      in order to obtain patterned projections onto a detector. Compressive sensing
      (CS) reconstruction algorithms are then used to recover the image. To date, the
      coded illumination patterns used in conventional CT systems have been random.
      This paper addresses the code optimization problem for general tomography imaging
      based on the point spread function (PSF) of the system, which is used as a
      measure of the sensing matrix quality which connects to the restricted isometry
      property (RIP) and coherence of the sensing matrix. The methods presented are
      general, simple to use, and can be easily extended to other imaging systems.
      Simulations are presented where the peak signal to noise ratios (PSNR) of the
      reconstructed images using optimized coded apertures exhibit significant gain
      over those attained by random coded apertures. Additionally, results using real X
      ray tomography projections are presented.

PMID- 29041334
TI  - Inverse incoherent engineering.
AB  - We propose a protocol to construct shortcuts of adiabaticity for open quantum
      systems in unitary evolution. Using the dynamical invariants of open quantum
      systems, we design a convenient form of the driver Hamiltonian to accelerate the
      adiabatic decoherence free subspaces scheme (TDFs) and engineer a quantum state
      from the initial state into the target state. Since the trajectory of TDFSs is
      determined by the incoherent control process, we would like to call it as the
      inverse incoherent engineering protocol. We apply the method to a two-qubits
      system which interacts with a time-dependent vacuum squeezed field to prepare
      some maximally entangled states of it. The results illustrate that our protocol
      can be used both in the adiabatic and nonadiabatic regime with perfect fidelity.

PMID- 29041335
TI  - Nanostructured GaAs solar cells via metal-assisted chemical etching of emitter
      layers.
AB  - GaAs solar cells with nanostructured emitter layers were fabricated via metal
      assisted chemical etching. Au nanoparticles produced via thermal treatment of Au
      thin films were used as etch catalysts to texture an emitter surface with
      nanohole structures. Epi-wafers with emitter layers 0.5, 1.0, and 1.5 um in
      thickness were directly textured and a window layer removal process was performed
      before metal catalyst deposition. A nanohole-textured emitter layer provides
      effective light trapping capabilities, reducing the surface reflection of a
      textured solar cell by 11.0%. However, because the nanostructures have high
      surface area to volume ratios and large numbers of defects, various photovoltaic
      properties were diminished by high recombination losses. Thus, we have studied
      the application of nanohole structures to GaAs emitter solar cells and
      investigated the cells' antireflection and photovoltaic properties as a function
      of the nanohole structure and emitter thickness. Due to decreased surface
      reflection and improved shunt resistance, the solar cell efficiency increased
      from 4.25% for non-textured solar cells to 7.15% for solar cells textured for 5
      min.

PMID- 29041336
TI  - Graphene-assisted high-efficiency liquid crystal tunable terahertz metamaterial
      absorber.
AB  - In this paper, few-layer porous graphene is integrated onto the surface of a
      metasurface layer to provide a uniform static electric field to efficiently
      control liquid crystal, thereby enabling flexible metamaterial designs. We
      demonstrate a tunable cross-shaped metamaterial absorber with different arm
      lengths driven by this combined metasurface and graphene electrode. The resulting
      absorber supports a resonant frequency tunable from 0.75 to 1 THz with a high
      quality factor, and amplitude modulation of ~80% at these frequencies with an
      applied voltage of 10 V. Furthermore, the near-field intensity and hot spot
      distribution can be manipulated over a broad range.

PMID- 29041337
TI  - Tunable Fano resonance based on grating-coupled and graphene-based Otto
      configuration.
AB  - A grating-coupled Otto configuration consisting of multilayer films including a
      few layers of graphene and a germanium prism is proposed. A sharp and sensitive
      Fano resonance appears when a graphene surface plasmon polaritons (GSPPs) mode
      from the graphene-dielectric interface couple with the planar waveguide (PWG)
      mode. We utilize the classical harmonic oscillator (CHO) to explain Fano
      resonance and study the influence of various parameters of the configuration on
      the reflection spectra. The highly sensitive sensor can be achieved by
      introducing detected materials into Otto structure. In addition, we investigated
      the effects from material loss arising in our designs. All of the simulations are
      performed by a finite element method (FEM).

PMID- 29041338
TI  - Semi-analytical approach to supermode spatial solitons formation in nematic
      liquid crystals.
AB  - We study light propagation in nematic liquid crystals in the context of spatial
      optical solitons formation. We propose a simple analytical model with
      multiplicative nonlinearity, which represents (qualitatively) the liquid crystal
      response by comprising the competition between focusing (reorientational) and
      defocusing (thermal) nonlocal nonlinearities. We show that at sufficiently high
      input power the interplay between both nonlinearities leads to the formations of
      two-peak solitons, which represent supermodes of the self-induced extended
      waveguide structure. We explain the beam splitting mechanism, discuss threshold
      effects and conclude that similar phenomena might be present in other media with
      competing nonlocal nonlinearities.

PMID- 29041339
TI  - Analysis of material selection on dielectric metasurface performance.
AB  - Dielectric metasurfaces are ultra-thin devices that can shape optical wavefronts
      with extreme control. While an assortment of materials possessing a wide range of
      dielectric constants have been proposed and implemented, the minimum dielectric
      contrast required for metasurfaces to achieve high-efficiency performance, for a
      given device function and feature size constraint, is unclear. In this Article,
      we examine the impact of dielectric material selection on metasurface efficiency
      at optical frequencies. As a model system, we design transmissive, single-layer
      periodic metasurfaces (i.e., metagratings) using topology optimization, and we
      sweep device thickness and light deflection angle for differing material types.
      We find that for modest deflection angles below 40 degrees, materials with
      relatively low dielectric constants near 4 can be used to produce metagratings
      with efficiencies over 80%. However, ultra-high-efficiency devices designed for
      large deflection angles and multiple functions require materials with high
      dielectric constants comparable to silicon. We also identify, for all materials,
      a minimum device thickness required for optimal metagrating performance that
      scales inversely with dielectric constant. Our work presents materials selection
      guidelines for high-performance metasurfaces operating at visible and infrared
      wavelengths.

PMID- 29041340
TI  - Estimation of chlorophyll concentration in waters near Hokkaido using the linear
      combination method.
AB  - An inversion algorithm is implemented to retrieve the surface chlorophyll a (Chl)
      concentration using satellite observation data from the MODIS instrument. The
      algorithm employs a simple and flexible index (LCI) to combine with the Chl
      without explicit correction for aerosol scattering. To investigate the
      sensitivity of LCI to Chl and other influence factors, an oceanic radiative
      transfer model coupled with a comprehensive bio-optical module is developed. It
      is studied that the LCI is significantly linear to Chl and not sensitive to other
      influence factors, except in very low oceanic salinity or scattering angle
      conditions, where over a 12% relative difference of derived Chl exists. Inversion
      results show the retrieved Chl are highly consistent with the MODIS operational
      data products in waters near Hokkaido, with the correlation coefficient, root
      mean square deviation, and average percentage difference of 0.9702, 0.3756 mg m
      3, and 13.89%, respectively. Investigation of the validity of this algorithm with
      a variety of atmospheric conditions indicates that the residual influence of
      atmosphere on the LCI index, after Rayleigh scattering correction, is generally
      within +/- 0.001, allowing the retrieval error of Chl at less than 25% in most
      cases. A good comparison between retrieval and in situ measurements is also
      identified and implies that the retrieval accuracy via the LCI method depends on
      the linear combination coefficients used and the bio-optical module selected,
      while effects of polarization can be ignored.

PMID- 29041341
TI  - Interference-induced filament array in fused silica.
AB  - One- and two-dimensional filament arrays are obtained in fused silica by using
      two and three interfered femtosecond laser beams, respectively. By modulating the
      number, cross angle, and azimuth of the beams, the dimension, period,
      orientation, and geometry of the filament-array can be controlled. The multiple
      beams interference method provides a convenient and effective method to generate
      and control the filament array in optical media with multiple degrees of freedom
      but without any external pulse modulation or focal element.

PMID- 29041342
TI  - Holographic tomography with object rotation and two-directional off-axis
      illumination.
AB  - A hybrid system of holographic tomography, which utilizes rotation of a sample
      and two-directional, off-axis illumination is proposed. The applied type of
      illumination brings two major benefits. First, it offers theoretical potential
      for the resolution improvement with respect to conventional tomography. Second,
      it enables effective, numerical compensation of the defocus error, which is
      achieved with an accurate, noise-immune autofocusing. Hence, the main practical
      obstacle of hybrid tomography is removed and its high-resolution potential is put
      into practice. The utility of the proposed concept is experimentally demonstrated
      with the tomographic measurement of a photonic crystal fiber.

PMID- 29041343
TI  - Near-field edge fringes at sharp material boundaries.
AB  - We have studied the formation of near-field fringes when sharp edges of materials
      are imaged using scattering-type scanning near-field optical microscope (s-SNOM).
      The materials we have investigated include dielectrics, metals, a near-perfect
      conductor, and those that possess anisotropic permittivity and hyperbolic
      dispersion. For our theoretical analysis, we use a technique that combines full
      wave numerical simulations of tip-sample near-field interaction and signal
      demodulation at higher orders akin to what is done in typical s-SNOM experiments.
      Unlike previous tip-sample interaction near-field models, our advanced technique
      allows simulation of the realistic tip and sample structure. Our analysis
      clarifies edge imaging of recently emerged layered materials such as hexagonal
      boron nitride and transition metal dichalcogenides (in particular, molybdenum
      disulfide), as well as traditional plasmonic materials such as gold. Hexagonal
      boron nitride is studied at several wavelengths, including the wavelength where
      it possesses excitation of phonon-polaritons and hyperbolic dispersion. Based on
      our results of s-SNOM imaging in different demodulation orders, we specify
      resonant and non-resonant types of edges and describe the edge fringes for each
      case. We clarify near-field edge-fringe formation at material sharp boundaries,
      both outside bright fringes and the low-contrast region at the edge, and
      elaborate on the necessity of separating them from propagating waves on the
      surface of polaritonic materials.

PMID- 29041344
TI  - Bandwidth broadening of a graphene-based circular polarization converter by phase
      compensation.
AB  - We present a broadband tunable circular polarization converter composed of a
      single graphene sheet patterned with butterfly-shaped holes, a dielectric spacer,
      and a 7-layer graphene ground plane. It can convert a linearly polarized wave
      into a circularly polarized wave in reflection mode. The polarization converter
      can be dynamically tuned by varying the Fermi energy of the single graphene
      sheet. Furthermore, the 7-layer graphene acting as a ground plane can modulate
      the phase of its reflected wave by controlling the Femi energy, which provides
      constructive interference condition at the surface of the single graphene sheet
      in a broad bandwidth and therefore significantly broadens the tunable bandwidth
      of the proposed polarization converter.

PMID- 29041345
TI  - Ocean color retrieval from MWI onboard the Tiangong-2 Space Lab: preliminary
      results.
AB  - The Moderate-resolution Wide-wavelengths Imager (MWI) is the ocean color sensor
      onboard the Chinese Tiangong-2 Space Lab, which was launched on Sept. 15, 2016.
      The MWI is also an experimental satellite sensor for the Chinese next generation
      ocean color satellites, HY-1E and HY-1F, which are scheduled for launch around
      2021. With 100m spatial resolution and 18 bands in the visible light and infrared
      wavelengths, MWI provides high quality ocean color observations especially over
      coastal and inland waters. For the first time, this study presents some important
      results on water color products generated from the MWI for the oceanic and inland
      waters. Preliminary validation in turbid coastal and inland waters showed good
      agreement between the MWI-retrieved normalized water-leaving radiances (Lwn) and
      in situ data. Further, the MWI-retrieved Lwn values compared well with the GOCI
      retrieved Lwn values, with the correlation coefficient greater than 0.90 and mean
      relative differences smaller than 26.63% (413 nm), 4.72% (443 nm), 3.69% (490
      nm), 7.15% (565 nm), 9.45% (665 nm), 8.11% (682.5 nm), 14.68% (750 nm) and 18.55%
      (865 nm). As for the Level 2 product (e.g, total suspended matter TSM) in turbid
      Yangtze River Estuary and Hangzhou Bay waters, the relative difference between
      MWI and GOCI-derived TSM values was ~18.59% with the correlation coefficient of
      0.956. In open-oceanic waters, the retrieved MWI-Chla distributions were well
      consistent with the MODIS/Aqua and VIIRS Chla values products and resolved finer
      spatial structures of phytoplankton blooms. This study provides encouraging
      results for the MWI's performance and operational applications in oceanic and
      inland regions.

PMID- 29041346
TI  - Bessel-correlated supercontinuum fields.
AB  - We examine the spatial coherence properties of supercontinuum fields generated by
      illuminating rotating bulk media with intense pulsed beams. Theoretical models
      are presented, which indicate the possibility of generating a class of Bessel
      correlated fields (in time-averaged sense) using tilted plane-parallel glass
      plates and wedges as media for generation of supercontinuum radiation. In special
      cases, the ensuing fields have a strictly identical functional form in the
      spatial and angular domains. Some of the main results are verified experimentally
      by measuring the spatial coherence properties of bulk-generated supercontinuum
      fields using a wavefront-folding interferometer.

PMID- 29041347
TI  - Plasmonic in-plane total internal reflection: azimuthal polarized beam focusing
      and application.
AB  - Due to the characteristic of surface plasmon polaritons (SPP) excitation, radial
      polarized beams and circular polarized beams are widely used for plasmonic lens
      and plasmonic near field focusing. In this paper, a plasmonic lens based on in
      plane total internal reflection (TIR) scheme is proposed and numerically
      demonstrated to achieve the simultaneous nanofocusing of azimuthal and radial
      polarized beams. By means of the in-plane TIR mechanism, the operation bandwidth
      of lens ranges from visible light to mid-infrared. The proposed structure has
      been utilized in the design of a plasmonic liquid refractive index sensor and is
      expected to find potential applications in near-field optical energy focusing,
      near-field imaging and sensing.

PMID- 29041348
TI  - Efficient 1620 nm continuous-wave laser operation of Czochralski grown
      Er:Yb:Lu2Si2O7 crystal.
AB  - Efficient continuous-wave diode-pumped laser operation of Czochralski grown
      Er:Yb:Lu2Si2O7 crystal is reported. Polarized absorption and emission spectra,
      fluorescence lifetimes, and energy transfer efficiency from Yb3+ to Er3+ were
      determined. A maximal output power of 522 mW was achieved at 1620 nm with slope
      efficiency of 15.8% and absorbed pump threshold of 470 mW. Among the Er3+ and
      Yb3+ co-doped materials with long fluorescence lifetimes of the upper level
      4I13/2, which are candidates for gain media of pulsed laser around 1.55 MUm with
      high energy, comprehensive performance of the Er:Yb:Lu2Si2O7 crystal is the best
      till now.

PMID- 29041349
TI  - High repetition rates optically active langasite electro-optically Q-switched
      laser at 1.34 MUm.
AB  - An electro-optically Q-switched pulsed laser at 1.34 MUm with a repetition rate
      of 100 kHz applying optically active langasite (La3Ga5SiO14) crystal has been
      reported. With Nd:YVO4 as laser crystal, the electro-optically Q-switched pulsed
      lasers were obtained with the maximum repetition rate of 100 kHz, maximum average
      output power of 2.42 W, and a minimum pulse width of 2.4 ns. Based on the theory
      of rate equations, the optimal pulse energy of the electro-optical Q-switching
      could be calculated. The experimental results have been found to be matched well
      with the theoretical calculations. To the best of our knowledge, this work
      presents the highest repetition rate and shortest pulse width which are achieved
      by an electric-optic LGS Q-switching at the wavelength of 1.34 MUm, and it
      enriches the material categories for generating the high repetition rate pulsed
      laser.

PMID- 29041350
TI  - Complete measurement of spatiotemporally complex multi-spatial-mode ultrashort
      pulses from multimode optical fibers using delay-scanned wavelength-multiplexed
      holography.
AB  - We introduce a simple delay-scanned complete spatiotemporal intensity-and-phase
      measurement technique based on wavelength-multiplexed holography to characterize
      long, complex pulses in space and time. We demonstrate it using pulses emerging
      from multi-mode fiber. This technique extends the temporal range and spectral
      resolution of the single-frame STRIPED FISH technique without using an otherwise
      required expensive ultranarrow-bandpass filter. With this technique, we measured
      the complete intensity and phase of up to ten fiber modes from a multi-mode fiber
      (normalized frequency V ~10) over a ~3ps time range. Spatiotemporal complexities
      such as intermodal delay, modal dispersion, and material dispersion were also
      intuitively displayed by the retrieved results. Agreement between the
      reconstructed color movies and the monitored time-averaged spatial profiles
      confirms the validity to this delay-scanned STRIPED FISH method.

PMID- 29041351
TI  - Fast response and transparent optically isotropic liquid crystal diffraction
      grating.
AB  - We have demonstrated an electrically tunable less polarization sensitive and fast
      response nanostructured polymer dispersed liquid crystal (nano-PDLC) diffraction
      grating. Fabricated nano-PDLC is optically transparent in visible wavelength
      regime. The optical isotropic nature was increased by minimizing the liquid
      crystal droplet size below visible wavelength thereby eliminated scattering.
      Diffraction properties of in-plane switching (IPS) and fringe-field switching
      (FFS) cells were measured and compared with one another up to four orders. We
      have obtained a pore-type polymer network constructed by highly interlinked
      polymer beads at which the response time is improved by strong interaction of
      liquid crystal molecules with polymer beads at interface. The diffraction pattern
      obtained by transparent nano-PDLC film has several interesting properties such as
      less polarization dependence and fast response. This device can be used as
      transparent tunable diffractor along with other photonic application.

PMID- 29041352
TI  - Physical-geometric optics method for large size faceted particles.
AB  - A new physical-geometric optics method is developed to compute the single
      scattering properties of faceted particles. It incorporates a general absorption
      vector to accurately account for inhomogeneous wave effects, and subsequently
      yields the relevant analytical formulas effective and computationally efficient
      for absorptive scattering particles. A bundle of rays incident on a certain facet
      can be traced as a single beam. For a beam incident on multiple facets, a
      systematic beam-splitting technique based on computer graphics is used to split
      the original beam into several sub-beams so that each sub-beam is incident only
      on an individual facet. The new beam-splitting technique significantly reduces
      the computational burden. The present physical-geometric optics method can be
      generalized to arbitrary faceted particles with either convex or concave shapes
      and with a homogeneous or an inhomogeneous (e.g., a particle with a core)
      composition. The single-scattering properties of irregular convex homogeneous and
      inhomogeneous hexahedra are simulated and compared to their counterparts from two
      other methods including a numerically rigorous method.

PMID- 29041353
TI  - Yb3+ heavily doped photonic crystal fiber lasers prepared by the glass phase
      separation technology.
AB  - We report a Yb3+ heavily doped photonic crystal fiber with 30 MUm core diameter
      manufactured for the first time by an alternative technique. Silica core rods
      with a diameter of 3 mm and a length of 280 mm were prepared by the sodium
      borosilicate glass phase-separation technology. The measurements show that the
      fiber has an Yb3+ concentration of 22810 ppm by weight, and a resultant
      absorption of approximately 8.5 dB/m at 976 nm. The Yb3+ ions are distributed
      throughout the fiber core with an excellent homogeneity. The laser performance
      demonstrates a high slope efficiency of 64.5% for laser emission at 1033.4 nm and
      a low power threshold of 3 W within a short fiber length of 1 m. This novel
      approach provides an alternative means of preparing large active silica rods with
      high doping levels and excellent material homogeneity for large mode area fibers
      with complex designs.

PMID- 29041354
TI  - All-dielectric KTiOPO4 metasurfaces based on multipolar resonances in the
      terahertz region.
AB  - We employ ferroelectrics to study the multipolar scattering in all-dielectric
      metasurfaces based on KTiOPO4 (KTP) micro-disks for efficient manipulation of
      electromagnetic waves in the THz spectral region (0.6-1.5 THz). By adjusting the
      aspect ratio of the disks near the multipolar resonances, we show that the KTP
      disk array can form a multifunctional metasurface that covers the entire range of
      the electromagnetic response with resonantly enhanced anisotropic properties. The
      proposed ferroelectric metasurfaces will provide a versatile platform to
      manipulate THz waves, and open possibilities to monolithically combine it with
      THz generation.

PMID- 29041355
TI  - Optical readout of hydrogen storage in films of Au and Pd.
AB  - For hydrogen sensor and storage applications, films of Au and Pd were (i) co
      sputtered at different rates or (ii) deposited in a sequentially alternating
      fashion to create a layered structure on a cover glass. Peculiarities of hydrogen
      uptake and release were optically monitored using 1.3 MUm wavelength light.
      Increase of optical transmission was observed for hydrogenated Pd-rich films of
      10-30 nm thickness. Up to a three times slower hydrogen release took place as
      compared with the hydrogen uptake. Compositional ratio of Au:Pd and thermal
      treatment of films provided control over the optical extinction changes and
      hydrogen uptake/release time constants. Higher uptake and release rates were
      observed in the annealed Au:Pd films as compared to those deposited at room
      temperature and were faster for the Auricher films. Three main parameters
      relevant for sensors: sensitivity, selectivity, stability (reproducibility) are
      discussed together with the hydrogenation mechanism in Au:Pd alloys.

PMID- 29041356
TI  - On the quantification of spatial resolution for three-dimensional computed
      tomography of chemiluminescence.
AB  - Three-dimensional computed tomography of chemiluminescence (CTC) for combustion
      diagnostics is attracting a surged research interest due to recent progress in
      sensor technologies and reduced costs of high-speed cameras. For example, it has
      been applied to recover the 3D distributions of intermediate chemical species
      such as CH* and OH*, heat release rate, and flame topology. Although these
      applications were demonstrated to be successful, there are still a few drawbacks
      of this technique that have not be cured. For example, to the best of the
      authors' knowledge, all the imaging models that have been developed so far ignore
      the imperfections of cameras such as lens distortion and skewness. However, this
      will unavoidably introduce errors into the weight matrix. In addition, spatial
      resolution of a CTC system is a critical performance parameter. However, it has
      only been studied qualitatively and no quantitative quantification method is
      reported so far. This work aims to solve these problems by improving the imaging
      model and developing a method based on edge spread function for the
      quantification of spatial resolution. Although this work is conducted under the
      context of CTC for combustion diagnostics, it also provides useful insights for
      other tomographic modalities such as volumetric laser-induced fluorescence and
      tomographic laser-induced incandescence.

PMID- 29041357
TI  - Dynamic position shifts of X-ray emission from a water film induced by a pair of
      time-delayed femtosecond laser pulses.
AB  - Femtosecond double-pulsed laser excitation of a water film in air showed
      enhancements of X-ray intensity as compared with single pulse irradiation. The
      position of the highest yield of X-rays strongly depends on temporal separation
      between the pre-pulse and the main-pulse (energy ratios where ~ 1 : 10). The
      strongest X-ray emission was observed at 10-15 ns delay of the main-pulse.
      Nanoscale roughening of water surface can account for the observation.

PMID- 29041358
TI  - Sub 23 MUHz instantaneous linewidth and frequency stability measurements of the
      beat note from an offset phase locked single frequency heterodyned Nd:YAG laser
      system.
AB  - We report, what is to the best of our knowledge, the narrowest instantaneous
      linewidth measurement of the beat frequency between two phase locked heterodyned
      1.319 MUm Nd:YAG lasers. At both 65 kHz and 31.7 GHz beat frequencies, we
      measured the instantaneous 3 dB linewidth of the optically-generated microwave
      tones to be < 22.8 MUHz, limited only by the minimum instrument resolution. Allan
      deviation measurements indicate that the laser system follows a 5 MHz quartz
      reference oscillator to stability levels of sigmay (1s) = 8.4 * 10-12. At 10.24
      GHz, the laser system follows a sapphire loaded cavity oscillator to stability
      levels of sigmay (1s) = 1.6 * 10-11. For these measurements, the optical beat
      note closely follows the linewidth and stability of the driving microwave
      frequency reference.

PMID- 29041359
TI  - Variable self-powered light detection CMOS chip with real-time adaptive tracking
      digital output based on a novel on-chip sensor.
AB  - This paper provides a solution for a self-powered light direction detection with
      digitized output. Light direction sensors, energy harvesting photodiodes, real
      time adaptive tracking digital output unit and other necessary circuits are
      integrated on a single chip based on a standard 0.18 um CMOS process. Light
      direction sensors proposed have an accuracy of 1.8 degree over a 120 degree
      range. In order to improve the accuracy, a compensation circuit is presented for
      photodiodes' forward currents. The actual measurement precision of output is
      approximately 7 ENOB. Besides that, an adaptive under voltage protection circuit
      is designed for variable supply power which may undulate with temperature and
      process.

PMID- 29041360
TI  - Surface topography acquisition method for double-sided near-right-angle
      structured surfaces based on dual-probe wavelength scanning interferometry.
AB  - This paper proposes an approach to measure double-sided near-right-angle
      structured surfaces based on dual-probe wavelength scanning interferometry
      (DPWSI). The principle and mathematical model is discussed and the measurement
      system is calibrated with a combination of standard step-height samples for both
      probes vertical calibrations and a specially designed calibration artefact for
      building up the space coordinate relationship of the dual-probe measurement
      system. The topography of the specially designed artefact is acquired by
      combining the measurement results with white light scanning interferometer (WLSI)
      and scanning electron microscope (SEM) for reference. The relative location of
      the two probes is then determined with 3D registration algorithm. Experimental
      validation of the approach is provided and the results show that the method is
      able to measure double-sided near-right-angle structured surfaces with nanometer
      vertical resolution and micrometer lateral resolution.

PMID- 29041361
TI  - Tapered silicon core fibers with nano-spikes for optical coupling via spliced
      silica fibers.
AB  - Reported here is the fabrication of tapered silicon core fibers possessing a nano
      spike input that facilitates their seamless splicing to conventional single mode
      fibers. A proof-of-concept 30 um cladding diameter fiber-based device is
      demonstrated with nano-spike coupling and propagation losses below 4 dB and 2
      dB/cm, respectively. Finite-element-method-based simulations show that the nano
      spike coupling losses could be reduced to below 1 dB by decreasing the cladding
      diameters down to 10 um. Such efficient and robust integration of the silicon
      core fibers with standard fiber devices will help to overcome significant
      barriers for all-fiber nonlinear photonics and optoelectronics.

PMID- 29041362
TI  - Generating liquid nanojets from copper by dual laser irradiation for ultra-high
      resolution printing.
AB  - When the energy of a short laser pulse is localized in a fluid material, a flow
      motion is induced that can lead to the generation of free-surface jets. This
      nozzle-free jetting process is exploited to print conductive materials, typically
      metal nanoparticle inks, but this approach remains limited to the transfer of low
      viscosity fluids with a minimum feature size of few micrometers. We introduce a
      dual-laser method to achieve reproducible high-aspect-ratio jets from thin solid
      films. A first laser irradiation induces the melting of copper thin films and a
      second synchronized short pulse irradiation initiates the jetting process. Using
      time-resolved microscopy, we investigate the influence of the film thickness on
      the flow motion mechanisms and the ejection dynamics. For a wide range of laser
      fluences, we present observations similar to those obtained when the jets are
      generated by a single laser pulse from liquid donor films. The use of a solid
      film allows reducing the film thickness and then the volume of transferred
      material. Finally, we analyze these results in the perspective of using this
      double pulse LIFT technique for additive manufacturing of nano-micro-structures.
      Stable jets are formed from the copper films over distances exceeding 50-MUm and
      are exploited to demonstrate periodic printing of 1.5-MUm diameter droplets.

PMID- 29041363
TI  - Transmission and plasmonic resonances on quasicrystal metasurfaces.
AB  - The control of light-matter interaction in metasurfaces offers an unexplored
      potential for the excitation and manipulation of light. Here, we combine
      experimental terahertz time-domain spectroscopy and near-field scanning terahertz
      microscopy to demonstrate the role of reciprocal vectors in the transmission and
      plasmonic resonances of quasicrystal metasurfaces. An investigation of two
      dimensional metasurface structures with different rotationally symmetric
      quasicrystal arrangements demonstrates that the transmission minima resulting
      from Wood's anomaly are directly related to the surface plasmon resonances. We
      also find that the surface plasmon resonances of the quasicrystal metasurface
      were determined by the reciprocal vectors, which could be well explained by the
      coupling condition of the resonances, and the characteristic frequencies remain
      un-shifted under various slit sizes. Our findings demonstrate a new potential in
      developing novel plasmonic metasurfaces.

PMID- 29041364
TI  - Perfectly matched layers for nonlocal media with hydrodynamic-Drude description:
      a transformation optics approach.
AB  - We develop a transformation optics theory for the nonlocal media in the
      hydrodynamic Drude model by generalizing the free-electron current density
      equation to a transformation invariant form. Applying the transformation optics
      theory, perfectly matched layers (PMLs) for the nonlocal media are theoretically
      formulated and implemented in frequency domain with finite element method. The
      nonlocal PMLs are shown to absorb outgoing surface and volume plasmons without
      inducing unphysical reflections. The effectiveness of the nonlocal PMLs is
      quantitatively demonstrated by the behaviors that the numerical errors
      continuously approach zero with increasing linear mesh density.

PMID- 29041365
TI  - Condensation phenomenon detection through surface plasmon resonance.
AB  - The aim of this work is to optically detect the condensation of acetone vapor on
      an aluminum plate cooled down in a two-phase environment (liquid/vapor). Sub
      micron period aluminum based diffraction gratings with appropriate properties,
      exhibiting a highly sensitive plasmonic response, were successfully used for
      condensation experiments. A shift in the plasmonic wavelength resonance has been
      measured when acetone condensation on the aluminum surface takes place due to a
      change of the surrounding medium close to the surface, demonstrating that the
      surface modification occurs at the very beginning of the condensation phenomenon.
      This paper presents important steps in comprehending the incipience of condensate
      droplet and frost nucleation (since both mechanisms are similar) and thus to
      control the phenomenon by using an optimized engineered surface.

PMID- 29041366
TI  - Spectral element boundary integral method with periodic layered medium dyadic
      Green's function for multiscale nano-optical scattering analysis.
AB  - In this work, we propose a numerical solver combining the spectral element -
      boundary integral (SEBI) method with the periodic layered medium dyadic Green's
      function. The periodic layered medium dyadic Green's function is formulated under
      matrix representation. The surface integral equations (SIEs) are then implemented
      as the radiation boundary condition to truncate the top and bottom computation
      domain. After describing the interior computation domain with the vector wave
      equations, and treating the lateral boundaries with Bloch periodic boundary
      conditions, the whole computation domains are discretized with mixed-order Gauss-
      Lobatto-Legendre basis functions in the SEBI method. This method avoids the
      discretization of the top and bottom layered media, so it can be much more
      efficient than conventional methods. Numerical results validate the proposed
      solver with fast convergence throughout the whole computation domain and good
      performance for typical multiscale nano-optical applications.

PMID- 29041367
TI  - Swinging multi-source industrial CT systems for aperiodic dynamic imaging.
AB  - The goal of this paper is to develop a new architecture for industrial computed
      tomography (ICT) aiming at dynamically imaging an aperiodic changing object. We
      propose a data acquisition approach with multiple x-ray source/detector pairs
      targeting a continuously changeable object with corresponding timeframes. In this
      named swinging multi-source CT (SMCT) structure, each source and its associated
      detector swing forth and back within a certain angle for CT scanning. In the SMCT
      system design, we utilize a circular journal bearing based setup to replace the
      normal CT slip ring by weakening the scanning speed requirement. Inspired by the
      prior image constrained compressed sensing (PICCS) algorithm, we apply a modified
      PICCS algorithm for the SMCT (SM-PICCS). Our numerical simulation and realistic
      specimen experiment studies demonstrate the feasibility of the proposed approach.

PMID- 29041368
TI  - Laser-writing of ring-shaped waveguides in BGO crystal for telecommunication
      band.
AB  - We report on the fabrication of ring-shaped waveguides operating at the
      telecommunication band in a cubic Bi4Ge3O12 (BGO) crystal by using technique of
      femtosecond laser writing. In the regions of laser written tracks in BGO crystal,
      positive refractive index is induced, resulting in so-called Type I
      configuration. The modal profiles are within the designed track cladding with
      ring-shaped geometries, which are analogous to circular optical lattices. The
      homogenous guidance along both TE and TM polarizations has been obtained at
      telecommunication wavelength of 1.55 MUm. Both straight and S-curved waveguiding
      structures have been produced with ring-shaped configurations. This work paves
      the way to fabricate complex photonic networks for telecommunications by using
      ring-shaped waveguides in compact chips.

PMID- 29041369
TI  - On the potential of solid state LED strips utilizing an organic color converter
      for non-line of sight visible light communication.
AB  - LED strip lighting can provide high quality uniform shadow-free diffuse lighting
      at low cost as numerous emission sources are controlled by a single transformer.
      Organic LEDs offer the additional advantages of UV free emission and, for visible
      light communication, picosecond fluorescent lifetimes allowing the whole visible
      spectrum to be used without filters. Using parameters determined experimentally
      for solid-state LED strip lighting and fluorescent lifetimes typical of organic
      phosphors as the input for a Monte Carlo based ray-tracing simulation, we
      evaluate the potential bandwidths obtainable for indoor communication. Our work
      suggests that raw data transfer rates of 4 to 10 Mbps are obtainable in a
      standard 5m by 5m by 3m room compatible with Internet of Things (IoT)
      applications.

PMID- 29041370
TI  - Experimental demonstrations of 30Gb/s/lambda digital orthogonal filtering
      multiplexed multiple channel transmissions over IMDD PON systems utilizing 10G
      class optical devices.
AB  - By utilizing digital orthogonal filtering (DOF) in the digital domain, we report,
      for the first time, experimental demonstrations of aggregated 30.078Gb/s/lambda
      transmissions of DOF-multiplexed spectrally-overlapped and/or frequency gapless
      six channels over IMDD PON systems incorporating off-the-shelf and low-cost 10G
      class optical devices. Experimental results show that simple adaptive channel
      power loading implemented in the digital domain enables very similar transmission
      performances of individual channels regardless of their locations in the digital
      filter space. As a direct result of the interplay between the transmission system
      associated negative chromatic dispersion and the intensity modulation-induced
      frequency chirp, negative power penalties of >0.2dB are experimentally observed
      for all the involved channels under various transmission system configurations.
      In addition, excellent performance robustness of the demonstrated systems is also
      obtainable for various transmission distances up to 45km.

PMID- 29041371
TI  - Dependence of measured audio-band squeezing level on local oscillator intensity
      noise.
AB  - We investigate the dependence of the measured squeezing level on the local
      oscillator (LO) intensity noise. The theoretical results indicate that it
      produces a large measurement error with the increase of the LO intensity noise,
      but the measurement error has immunity to the product P of the common mode
      rejection ratio (CMRR) with the LO intensity noise. According to the
      investigation results and the LO intensity noise, we employ a detector with the
      CMRR of 67 dB to detect the quantum noise at audio frequencies, the product P of
      the CMRR with the LO intensity noise is 20 dB below the shot noise limit (SNL),
      which can induce the measurement error of 0.1 dB for 10 dB of squeezing. Finally,
      the squeezing level measured at 15.2 kHz is 9.9 +/- 0.2 dB. The influence of the
      intensity noise of the LO, and the electronic noise of the detector is
      subtracted, the inferred squeezing level is approximately 10.2 +/- 0.2 dB. It is
      extremely important to quantify the requirements of the CMRR of the detector for
      measuring the squeezing at audio frequency and inferring the real squeezing
      level.

PMID- 29041372
TI  - Subwavelength imaging by a nonlinear negative refraction lens through four wave
      mixing.
AB  - We propose a new approach for subwavelength imaging using a nonlinear negative
      refraction lens based on four wave mixing process. Here a thin metal film is
      implemented as the nonlinear negative refraction lens to bend the incident signal
      waves to negatively refracted FWM ones according to the partial phase matching
      along its surface. The imaging process can be described by the nonlinear optical
      transfer function over the entire spatial spectra including the evanescent ones.
      Analytical calculations and numerical simulations are performed to demonstrate
      the capability of such imaging. Compared with the existing techniques, our method
      works on non-resonant condition over a broad range of spectrum, therefore, it may
      open up a new avenue for super-resolution imaging applications.

PMID- 29041373
TI  - Dual-band unidirectional reflectionless phenomena in an ultracompact non
      Hermitian plasmonic waveguide system based on near-field coupling.
AB  - Dual-band unidirectional reflectionlessness and coherent perfect absorption (CPA)
      are demonstrated in a non-Hermitian plasmonic waveguide system based on near
      field coupling between a single resonator and the resonant modes of two
      resonators showing an electromagnetically induced-transparency-like (EIT-like)
      effect. The non-Hermitian plasmonic system consists of three metal-insulator
      metal (MIM) resonators coupled to a MIM plasmonic waveguide.

PMID- 29041374
TI  - Coherent frequency bridge between visible and telecommunications band for vortex
      light.
AB  - In quantum communications, vortex photons can encode higher-dimensional quantum
      states and build high-dimensional communication networks (HDCNs). The interfaces
      that connect different wavelengths are significant in HDCNs. We construct a
      coherent orbital angular momentum (OAM) frequency bridge via difference frequency
      conversion in a nonlinear bulk crystal for HDCNs. Using a single resonant cavity,
      maximum quantum conversion efficiencies from visible to infrared are 36%, 15%,
      and 7.8% for topological charges of 0,1, and 2, respectively. The average
      fidelity obtained using quantum state tomography for the down-converted infrared
      OAM-state of topological charge 1 is 96.51%. We also prove that the OAM is
      conserved in this process by measuring visible and infrared interference
      patterns. This coherent OAM frequency-down conversion bridge represents a basis
      for an interface between two high-dimensional quantum systems operating with
      different spectra.

PMID- 29041375
TI  - Automatic fringe enhancement with novel bidimensional sinusoids-assisted
      empirical mode decomposition.
AB  - Fringe-based optical measurement techniques require reliable fringe analysis
      methods, where empirical mode decomposition (EMD) is an outstanding one due to
      its ability of analyzing complex signals and the merit of being data-driven.
      However, two challenging issues hinder the application of EMD in practical
      measurement. One is the tricky mode mixing problem (MMP), making the decomposed
      intrinsic mode functions (IMFs) have equivocal physical meaning; the other is the
      automatic and accurate extraction of the sinusoidal fringe from the IMFs when
      unpredictable and unavoidable background and noise exist in real measurements.
      Accordingly, in this paper, a novel bidimensional sinusoids-assisted EMD (BSEMD)
      is proposed to decompose a fringe pattern into mono-component bidimensional IMFs
      (BIMFs), with the MMP solved; properties of the resulted BIMFs are then analyzed
      to recognize and enhance the useful fringe component. The decomposition and the
      fringe recognition are integrated and the latter provides a feedback to the
      former, helping to automatically stop the decomposition to make the algorithm
      simpler and more reliable. A series of experiments show that the proposed method
      is accurate, efficient and robust to various fringe patterns even with poor
      quality, rendering it a potential tool for practical use.

PMID- 29041376
TI  - In-line and cascaded DWDM transmission using a 15dB net-gain polarization
      insensitive fiber optical parametric amplifier.
AB  - We demonstrate and characterize polarization-division multiplexed (PDM) DWDM data
      transmission for the first time in a range of systems incorporating a net-gain
      polarization-insensitive fiber optical parametric amplifier (PI-FOPA) for loss
      compensation. The PI-FOPA comprises a modified diversity-loop architecture to
      achieve 15dB net-gain, and up to 2.3THz (~18nm) bandwidth. Three representative
      systems are characterized using a 100Gb/s PDM-QPSK signal in conjunction with
      emulated DWDM neighbouring channels: (a) a 4x75km in-line fiber transmission
      system incorporating multiple EDFAs and a single PI-FOPA (b) N cascaded PI-FOPA
      amplification stages in an unlevelled Nx25km recirculating loop arrangement, with
      no EDFAs used within the loop signal path, and (c) M cascaded PI-FOPA
      amplification stages as part of an Mx75.6km gain-flattened recirculating loop
      system with the FOPA compensating for the transmission fiber loss, and EDFA
      compensation for loop switching and levelling loss. For the 4x75km in-line system
      (a), we transmit 45x50GHz-spaced signals ('equivalent' data-rate of 4.5Tb/s) with
      average OSNR penalty of 1.3dB over the band at 10-3 BER. For the unlevelled 'FOPA
      only' 25.2km cascaded system (b), we report a maximum of eight recirculations for
      all 10x100GHz-spaced signals, and five recirculations for 20x50GHz-spaced
      signals. For the 75.6km levelled system

PMID- 29041377
TI  - Modulator figure of merit for short reach data links.
AB  - The traditional Mach-Zehnder modulator (MZM) figure of merit (FOM) has been
      defined as (Vpi2)/upsilon3dBe, and works effectively for LiNbO3 long haul
      modulators. However, for plasma dispersion based electro-optic modulators, or any
      modulator that has an inherent relationship between its bandwidth, required drive
      voltage, and optical insertion loss/gain, this FOM is inappropriate. This is
      particularly true for short reach links with no optical amplification. In the
      following, we propose a new modulator FOM (M-FOM) based on device metrics that
      are essential for short-reach links, such as the peak-to-peak drive voltage,
      modulator rise-fall time, and relative optical modulation amplitude. Link
      sensitivity measurements from two MZMs that have different bandwidths and optical
      losses are compared using our M-FOM to demonstrate its utility. Furthermore, we
      present a novel application protocol of our M-FOM to provide deeper insight into
      the relative system impact that modulator performance has on data links with no
      optical amplification, by taking the ratio of M-FOMs from two modulators driven
      with the same radio frequency drive power.

PMID- 29041378
TI  - AlxIn1-xAsySb1-y photodiodes with low avalanche breakdown temperature dependence.
AB  - We report AlxIn1-xAsySb1-y PIN and Separate Absorption, Charge and Multiplication
      (SACM) avalanche photodiodes (APDs) with high temperature stability. This work is
      based on measurements of avalanche breakdown voltage of these devices for
      temperatures between 223 K and 363 K. Breakdown voltage temperature coefficients
      are shown to be lower than those of APDs fabricated with other materials with
      comparable multiplication layer thicknesses.

PMID- 29041379
TI  - Surface deformation recovery algorithm for reflector antennas based on geometric
      optics.
AB  - Surface deformations of large reflector antennas highly depend on elevation
      angle. This paper adopted a scheme with the ability to conduct measurement at any
      elevation angle: carrying an emission source, an unmanned aerial vehicle (UAV)
      scans the antenna on a near-field plane, meanwhile the antenna stays stationary.
      Near-field amplitude is measured in the scheme. To recover the deformation from
      the measured amplitude, this paper proposed a novel algorithm by deriving the
      deformation-amplitude equation, which reveals the relation between the surface
      deformation and the near-field amplitude. By the algorithm, a precise deformation
      recovery can be reached at a low frequency (<1GHz) through single near-field
      amplitude. Simulation results showed the high accuracy and adaptability of the
      algorithm.

PMID- 29041380
TI  - Efficient demodulation scheme for rolling-shutter-patterning of CMOS image sensor
      based visible light communications.
AB  - Recently even the low-end mobile-phones are equipped with a high-resolution
      complementary-metal-oxide-semiconductor (CMOS) image sensor. This motivates using
      a CMOS image sensor for visible light communication (VLC). Here we propose and
      demonstrate an efficient demodulation scheme to synchronize and demodulate the
      rolling shutter pattern in image sensor based VLC. The implementation algorithm
      is discussed. The bit-error-rate (BER) performance and processing latency are
      evaluated and compared with other thresholding schemes.

PMID- 29041381
TI  - White-light quantitative phase imaging unit: erratum.
AB  - We found an error in Fig. 1 of our article "White-light Quantitative Phase
      Imaging Unit." Here we publish the revised figure.

PMID- 29041382
TI  - Fourier factorization in the constitutive relations for modeling diffraction
      gratings with continuous permittivity profiles.
AB  - The validity of the Fourier factorization (FF) rules used in the constitutive
      relations in the Fourier modal method is analyzed for one-dimensional diffraction
      gratings made as a thin film with uniform thickness and several examples of
      continuous lateral profiles of permittivity. The comparison of the method using
      the correct FF rules with other FF choices demonstrates the validity of the FF
      rules for any inhomogeneous, not only discontinuous profile.

PMID- 29041383
TI  - Causality and information transfer in simultaneously slow- and fast-light media.
AB  - We demonstrate the simultaneous propagation of slow- and fast-light optical
      pulses in a four-wave mixing scheme using warm potassium vapor. We show that when
      the system is tuned such that the input probe pulses exhibit slow-light group
      velocities and the generated pulses propagate with negative group velocities, the
      information velocity in the medium is nonetheless constrained to propagate at, or
      less than, c. These results demonstrate that the transfer and copying of
      information on optical pulses to those with negative group velocities obeys
      information causality, in a manner that is reminiscent of a classical version of
      the no-cloning theorem. Additionally, these results support the fundamental
      concept that points of non-analyticity on optical pulses correspond to carriers
      of new information.

PMID- 29041384
TI  - Loss of phase and universality of stochastic interactions between laser beams.
AB  - Traditionally, interactions between laser beams or filaments were considered to
      be deterministic. We show, however, that in most physical settings, these
      interactions ultimately become stochastic. Specifically, we show that in the
      nonlinear propagation of laser beams, the shot-to-shot variation of the nonlinear
      phase shift increases with distance, and ultimately becomes uniformly distributed
      in [0, 2pi]. Therefore, if two beams travel a sufficiently long distance before
      interacting, it is not possible to predict whether they would intersect in- or
      out-of-phase. Hence, if the underlying propagation model is non-integrable,
      deterministic predictions and control of the outcome of the interaction become
      impossible. Because the relative phase between the two beams becomes uniformly
      distributed in [0, 2pi], however, the statistics of these stochastic interactions
      are universal and fully predictable. These statistics can be efficiently computed
      using a novel universal model for stochastic interactions, even when the noise
      distribution is unknown.

PMID- 29041385
TI  - Mode suppression of 53 dB and pulse repetition rates of 2.87 and 36.4 GHz in a
      compact, mode-locked fiber laser comprising coupled Fabry-Perot cavities of low
      finesse (F = 2).
AB  - Multiplication of the pulse repetition frequency (PRF) of a compact, mode-locked
      fiber laser by a factor as large as 25 has been achieved with two coupled Fabry
      Perot (FP) resonators of low finesse (F = 2). Reducing the FP finesse by at least
      two orders of magnitude, relative to previous pulse frequency multiplication
      architectures, has the effect of stabilizing the oscillator with respect to pulse
      to-pulse amplitude, dropped pulses, and other effects of cavity detuning.
      Coupling two Fabry-Perot cavities, each encompassing a 3.3-3.6 cm length of
      fiber, in a hybrid geometry resembling that of the coupled-cavity laser
      interferometer has yielded side mode suppressions >= 50 dB while simultaneously
      doubling the laser PRF to 2.87 GHz. Pulses approximately 3.9 ps in duration
      (FWHM) are emitted at intervals of 27.5 ps, and in groups (bursts) of pulses
      separated by 350 ps. Thus, the PRF within the pulse bursts is 36 GHz, a factor of
      25 greater than the free spectral range for a conventional mode-locked cavity
      having a length of 6.9 cm. Experimental data are in accord with simulations of
      the phase coherence and temporal behavior of the mode-locked pulses.

PMID- 29041386
TI  - Localized terahertz electromagnetically-induced transparency-like phenomenon in a
      conductively coupled trimer metamolecule.
AB  - We experimentally investigate the terahertz (THz) electromagnetically-induced
      transparency (EIT)-like phenomenon in a metamolecule (MM) of three-body system.
      This system involves a couple of geometrically identical split-ring resonators
      (SRRs) in orthogonal layout conductively coupled by a cut-wire resonator. Such a
      three-body system exhibits two frequency response properties upon to the
      polarization of incident THz beam: One is the dark-bright-bright layout to the
      horizontally polarized THz beam, where there is no EIT-like effect; the other is
      bright-dark-dark layout to the vertically polarized THz beam, where an EIT-like
      effect is observable. The transparency window can be tuned from 0.71 THz to 0.74
      THz by the displacement of cut-wire inside the trimer MM. A maximum of 7.5 ps
      group delay of THz wave is found at the transparent window of 0.74 THz. When the
      cut-wire moved to the mid-point of lateral-side of SRR, the EIT-like phenomenon
      disappears, this leads to a localized THz slow-light effect. The distribution of
      surface currents and electric energy reveals that the excited inductive
      capacitive (LC) oscillation of bright-SRR dominates the high frequency side-mode,
      which is isolated to the displacement of cut-wire resonator. However, the low
      frequency side-mode originates from the constructive hybridization of LC
      resonance in dark-SRR coupled with a localized S-shaped dipole oscillator, which
      is tunable by the displacement of cut-wire. As a consequence, the group delay as
      well as the spectral configuration of transparency window can be manipulated by
      tuning one side-mode while fixing the other. Such an experimental finding reveal
      the EIT-like effect in a conductively coupled three-body system and manifests a
      novel approach to achieve tunable THz slow-light device.

PMID- 29041387
TI  - Adaptive threshold decision for on-off keying transmission systems in atmospheric
      turbulence.
AB  - This paper investigates an adaptive threshold decision (ATD) scheme without the
      knowledge of channel state information (CSI) for optical wireless communication
      (OWC). Based on the low-pass characteristic of atmospheric turbulence channels, a
      low-pass filter is designed for the received signals, and the filtered signal can
      be employed as decision threshold. Theoretical analyses show that performance of
      ATD is very close to that with perfect CSI. Monte Carlo simulations demonstrate
      that the proposed scheme shows only 0.0221dB signal-to-noise (SNR) loss at most
      with Rytov variance of 0.05 and SNR of 21dB. An indoor experiment results are
      presented, which match well with that of theoretical prediction. The scheme is
      simple and without CSI, hence the efficient scheme makes the real-time
      implementation of high-speed transmissions for OWC based on ATD feasible.

PMID- 29041388
TI  - Optomechanical properties of GaAs/AlAs micropillar resonators operating in the 18
      GHz range.
AB  - Recent experiments demonstrated that GaAs/AlAs based micropillar cavities are
      promising systems for quantum optomechanics, allowing the simultaneous three
      dimensional confinement of near-infrared photons and acoustic phonons in the 18
      100 GHz range. Here, we investigate through numerical simulations the
      optomechanical properties of this new platform. We evidence how the Poisson's
      ratio and semiconductor/vacuum boundary conditions lead to very distinct features
      in the mechanical and optical three-dimensional confinement. We find a strong
      dependence of the mechanical quality factor and strain distribution on the
      micropillar radius, in great contrast to what is predicted and observed in the
      optical domain. The derived optomechanical coupling constants g0 reach ultra
      large values in the 106 rad/s range.

PMID- 29041389
TI  - Improved TKM-TR methods for PAPR reduction of DCO-OFDM visible light
      communications.
AB  - The dc-biased optical orthogonal frequency division multiplexing (DCO-OFDM)
      system is experimentally demonstrated as an appealing candidate in future visible
      light communication (VLC) system. However, the intrinsic high PAPR drawback that
      the DCO-OFDM system suffers from still needs to be addressed and few effective
      approach has been found so far. To deal with this problem, in this paper, the
      tone reservation (TR) technique based the time domain kernel matrix (TKM-TR)
      schemes for reducing the PAPR are studied and applied to DCO-OFDM system. Aiming
      at the drawback of its severe tailing in previous TKM-TR schemes, first an
      improved TKM-TR scheme is proposed, in which the peak regrowth caused by severe
      tailing is eliminated by optimizing the scaling factors. In addition, considering
      the clipping ratio (CR) value in TKM-TR scheme is greatly related to the PAPR
      reduction performance, an extensively used heuristic global optimization
      algorithm, the particle swarm optimization (PSO) method is employed in TKM-TR to
      obtain a better CR for more PAPR reduction. Simulation results show that the
      improved TKM-TR scheme can efficiently address the tailing problem in previous
      TKM-TR schemes and achieve better PAPR reduction. Moreover, due to the powerful
      searching ability, PSO based TKM-TR scheme achieves more PAPR reduction and lower
      bit error rate (BER).

PMID- 29041390
TI  - Self-gated mid-infrared short pulse upconversion detection for gas sensing.
AB  - Pulsed nonlinear-optical upconversion is used for mid-infrared signal detection.
      A setup for both mid-infrared generation and upconversion based on a single pump
      laser enables sensitive light detection and is utilized for gas spectroscopy.
      With the demonstrated pulsed setup, quantum efficiencies above 80 % for the
      upconversion of a Gaussian beam signal and 25 % for the upconversion of
      backscattered radiation are achieved and in agreement with theoretical
      predictions. Combined with efficient background suppression due to spectral and
      temporal gating, this results in highly sensitive detection of the infrared
      signals. As a demonstration of application, the presented system is used for
      methane sensing in an open path geometry, highlighting the potential for stand
      off leak detection with a concentration resolution better than 1.5 ppm.m.

PMID- 29041391
TI  - Ion-sensitive photonic-crystal nanolaser sensors.
AB  - In general, biochemical sensors based on photonic cavities are used to detect
      changes in the refractive index of the environment. In this study, however, a
      GaInAsP semiconductor photonic-crystal nanolaser sensor that we recently
      developed was found to detect not only the environmental refractive index but
      also the surface charge. In contrast to the pH sensitivity we reported
      previously, this is an ultra-sensitive detection mechanism capable of identifying
      proteins and deoxyribonucleic acids (DNA) at a femtomolar-order or lower
      concentrations. When the device is exposed to plasma or DNA solutions, the laser
      wavelength simultaneously changes with the zeta potential and the flat-band
      potential of the semiconductor surface. This indicates that the charged
      functional groups on the surface, which are formed by these treatments, modify
      the Schottky barrier near the semiconductor surface, trap the excited carriers in
      the barrier, and change the refractive index of the semiconductor via the carrier
      effects. These findings also suggest that some other photonic sensors may also
      exhibit similar electrochemical and optoelectronic effects.

PMID- 29041392
TI  - Micro-hyperboloid lensed fibers for efficient coupling from laser chips.
AB  - A novel technique is presented for producing micro-hyperboloid lensed fibers for
      efficient coupling to semiconductor laser chips. A three-step process including a
      precision mechanical grinding, a spin-on-glass (SOG) coating and an electrostatic
      pulling process is used to form the hyperboloid lens structure on a flat-end
      single mold fiber (SMF) with the core diameter of 6.6 MUm. Micro-hyperboloid
      lensed fibers with tunable radii of curvature around 4.18 - 4.83 MUm can be
      formed on the SMF end face. A high average coupling efficiency around 80% and low
      coupling variation of 0.116 +/- 0.044% are obtained for the produced fibers. The
      developed method is efficient to produce micro-hyperboloid lensed fibers for high
      performance light coupling between the SMF and the semiconductor diode lasers.

PMID- 29041393
TI  - Half-sized cylindrical invisibility cloaks using double near zero slabs with
      realistic material size and properties.
AB  - A method is introduced to miniaturize invisibility cloaks by 50% using wave
      tailoring and finite/non-zero wave impedance of double near zero (DNZ) slabs.
      Unlike previous works, which use thick dielectric matching layers to miniaturize
      internal cloaks, the proposed technique is applied to both internal and external
      cylindrical cloaks using a thin and short DNZ slab to change cloaks' shapes to
      half-cylinder shells. Moreover, sets of structures are introduced for the half
      sized cloaks to enable using feasible-to-fabricate structures with the help of a
      rigorous theoretical analysis, which is validated via full-wave simulations. All
      of the presented results show that the proposed half cloaks can function
      perfectly well. The sensitivity of half-sized cloaks to the length and material
      properties of the DNZ slab is investigated to find the shortest length and the
      highest values of the permittivity and permeability for the slab to have small
      yet realizable structures. The analysis shows that slabs with length as small as
      the diameter of the cloaks and constitutive parameters (permittivity and
      permeability) as high asepsilonslab=MUslab=0.1-0.1iand epsilonslab=MUslab=0.05
      0.04i for half-sized external cloaks and half-sized internal cloaks,
      respectively, can still considerably reduce the scattered fields. The effect of
      the loss and incident angle of the field on the performance of the miniaturized
      cloaks are also analyzed.

PMID- 29041394
TI  - Cavity-based aluminum nanohole arrays with tunable infrared resonances.
AB  - This work details the successful computational design, fabrication, and
      characterization of a cavity-based aluminum nanohole array. The designs
      incorporate arrays of aluminum nanoholes that are patterned on a dielectric
      coated (SiO2 or ZnSe) aluminum base mirror plane. This architecture provided a
      means of exploring the coupling of the localized resonances, exhibited by the
      aluminum nanohole array, with the cavity resonance that is generated within the
      dielectric spacer layer, which resides between the base plane mirror and the
      nanohole array. Rigorous coupled wave analysis (RCWA) was first used to
      computationally design the structures. Next, a range of lithographic techniques,
      including photolithography, E-beam lithography, and nanosphere lithography, were
      used to fabricate the structures. Finally, infrared spectroscopy and scanning
      electron microscopy (SEM) were used to characterize the spectral and structural
      properties of the multilayered devices, respectively. The overall goal of this
      study was to demonstrate our ability to design and fabricate aluminum-based
      structures with tunable resonances throughout the infrared region, i.e. from the
      short-wave through longwave infrared regions of the electromagnetic spectrum (1.5
      -12 um).

PMID- 29041395
TI  - Compact and stable real-time dual-wavelength digital holographic microscopy with
      a long-working distance objective.
AB  - We propose a compact dual wavelength digital holographic Microscopy (DHM) based
      on a long working distance objective, which enabling quantitative phase imaging
      of opaque samples with extended measurement range in one shot. The compactness of
      the configuration is achieved by constructing a miniature modified Michelson
      interferometer between the objective and the sample, and as a result it provides
      higher temporal stability than conventional dual wavelength DHM. In the setup,
      the propagation directions of two reference beams of different wavelengths can be
      independently adjusted, and thus two off axis interferograms having orthogonal
      fringe directions can be simultaneously captured through a monochrome CCD camera.
      The unambiguous vertical measurement range in optical path length is extended to
      8.338 MUm, the length of a synthetic wavelength, by selecting two wavelengths
      with a gap of 52 nm. The capability of the proposed setup is demonstrated with
      measurements of a standard 1.8 MUm height step as well as a moving micro
      staircase structure.

PMID- 29041396
TI  - Fiber-optic anemometer based on single-walled carbon nanotube coated tilted fiber
      Bragg grating.
AB  - In this work, a novel and simple optical fiber hot-wire anemometer based on
      single-walled carbon nanotubes (SWCNTs) coated tilted fiber Bragg grating (TFBG)
      is proposed and demonstrated. For the hot-wire wind speed sensor design, TFBG is
      an ideal in-fiber sensing structure due to its unique features. It is utilized as
      both light coupling and temperature sensing element without using any geometry
      modified or uncommon fiber, which simplifies the sensor structure. To further
      enhance the thermal conversion capability, SWCNTs are coated on the surface of
      the TFBG instead of traditional metallic materials, which have excellent thermal
      characteristics. When a laser light is pumped into the sensor, the pump light
      propagating in the core will be easily coupled into cladding of the fiber via the
      TFBG and strongly absorbed by the SWCNTs thin film. This absorption acts like a
      hot-wire raising the local temperature of the fiber, which is accurately detected
      by the TFBG resonance shift. In the experiments, the sensor's performances were
      investigated and controlled by adjusting the inherent angle of the TFBG, the
      thickness of SWCNTs film, and the input power of the pump laser. It was
      demonstrated that the developed anemometer exhibited significant light absorption
      efficiency up to 93%, and the maximum temperature of the local area on the fiber
      was heated up to 146.1 degrees C under the relatively low pump power of 97.76 mW.
      The sensitivity of -0.3667 nm/(m/s) at wind speed of 1.0 m/s was measured with
      the selected 12 degrees  TFBG and 1.6 MUm film.

PMID- 29041397
TI  - On-chip second-harmonic generation and broadband parametric down-conversion in a
      lithium niobate microresonator.
AB  - Nonlinear wavelength conversion is essential for many classical and quantum pho
      tonic applications. The underlying second-order nonlinear optical processes,
      however, generally exhibit limited spectral bandwidths that impact their
      application potential. Here we use a high-Q X-cut lithium niobate microdisk
      resonator to demonstrate both second-harmonic generation and spontaneous
      parametric down-conversion on chip. In particular, our lithium niobate
      microresonator, with its wide-range cyclic phase matching and rich optical mode
      structures, is able to achieve ultra-broadband spontaneous parametric down
      conversion, with a bandwidth over 400 nm, inferred from recorded spectra of the
      down-converted photons. The produced biphoton pairs exhibit strong temporal
      correlation, with a coincidence-to-accidental ratio measured to be 43.1. Our
      device is promising for integrated quantum photonics where optical frequency
      could be used as a degree of freedom for signal processing.

PMID- 29041398
TI  - Simultaneous multi-piston measurement method in segmented telescopes.
AB  - We propose a method to simultaneously detect the multi-piston between segments.
      The relation between the piston of any two segments and amplitude of the
      modulation transfer function (MTF) sidelobes (MTFnph) is derived. The piston can
      be retrieved by this relation after measuring the MTFnph. This method's capture
      range is the operating light's coherence length, the accuracy is 0.026lambda
      (lambda = 633 nm) RMS. The MTF model of a mask with sparse multi-subaperture
      configuration is established. The arrangement rules, to avoid the sidelobes
      overlapping, are obtained. The mask with a sparse 18 sub-aperture configuration
      is designed, which makes the MTF sidelobes distribution non-redundant.

PMID- 29041399
TI  - Dynamic fiber delivery of 3 W 160 fs pulses with photonic crystal hollow core
      fiber patchcord.
AB  - We report output characteristics of a connectorized hollow core photonics crystal
      fiber when it is subjected to coiling down to a 50 mm radius, bending, and
      torsion. We achieved coupling efficiency up to 73% with an output average power
      of 2 W and 24 nJ pulse energy. With optimized coupling, depolarization was as low
      as 7%. Coiling and bending of the photonic crystal patchcord introduces little
      distortion; torsion, however, changes the polarization drastically. To our
      knowledge, this is the first report on dynamic fiber delivery of fs pulses.

PMID- 29041400
TI  - High efficiency geometric-phase polarization fan-out grating on silicon.
AB  - We report the design, fabrication and characterization of a 1-by-5 geometric
      phase polarization fan-out grating for coherent beam combining at 1550 nm. The
      phase profile of the grating is accurately controlled by the local orientation of
      the binary subwavelength structure instead of the etching depth and profile
      empowering the grating to be more tolerant to fabrication errors. Deep-UV
      interference lithography on silicon offers an inexpensive, highly efficient and
      high damage threshold solution to fabricating large-area fan-out gratings than
      electron beam lithography (EBL) and photoalignment liquid crystals. The
      theoretical and experimental diffraction efficiency of the grating is 87% and
      85.7% respectively. Such a fan-out grating may find application to high-power
      beam combining in the infrared regime.

PMID- 29041401
TI  - Tailoring optical pulling force on gain coated nanoparticles with nonlocal
      effective medium theory.
AB  - We study the optical scattering force on the coated nanoparticles with gain core
      and nonlocal plasmonic shell in the long-wavelength limit, and demonstrate
      negative optical force acting on the nanoparticles near the symmetric and/or
      antisymmetric surface plasmon resonances. To understand the optical force
      behavior, we propose nonlocal effective medium theory to derive the equivalent
      permittivity for the coated nanoparticles with nonlocality. We show that the
      imaginary part of the equivalent permittivity is negative near the surface
      resonant wavelength, resulting in the negative optical force. The introduction of
      nonlocality may shift the resonant wavelength of the optical force, and
      strengthen the negative optical force. Two examples of Fano-like resonant
      scattering in such coated nanoparticles are considered, and Fano resonance
      induced negative optical force is found too. Our findings could have some
      potential applications in plasmonics, nano-optical manipulation, and optical
      selection.

PMID- 29041402
TI  - General design method of ultra-broadband perfect absorbers based on magnetic
      polaritons.
AB  - Starting from one-dimensional gratings and the theory of magnetic polaritons
      (MPs), we propose a general design method of ultra-broadband perfect absorbers.
      Based on the proposed design method, the obtained absorber can keep the spectrum
      average absorptance over 99% at normal incidence in a wide range of wavelengths;
      this work simultaneously reveals the robustness of the absorber to incident
      angles and polarization angles of incident light. Furthermore, this work shows
      that the spectral band of perfect absorption can be flexibly extended to near the
      infrared regime by adjusting the structure dimension. The findings of this work
      may facilitate the active design of ultra-broadband absorbers based on plasmonic
      nanostructures.

PMID- 29041403
TI  - Optical properties of black carbon aerosols encapsulated in a shell of sulfate:
      comparison of the closed cell model with a coated aggregate model.
AB  - At 532 nm wavelength, optical properties of black carbon (BC) particles mixed
      with sulfate are computed by use of two morphological models, a closed cell and a
      coated aggregate model. For high BC volume fractions f, both models yield
      comparable results. As more sulfate is added, some of the optical properties
      diverge. The backscattering depolarization ratio deltaL is particularly sensitive
      to the morphology. Comparison with field measurements suggests that the closed
      cell model underestimates deltaL; the coated aggregate model yields good results
      for intermediate and high values of f, but somewhat too high results for low f.
      This could be improved by taking the collapse of fractal structure with
      decreasing f into account.

PMID- 29041404
TI  - Noise characteristics of high power fiber-laser pumped femtosecond optical
      parametric generation.
AB  - We study, both numerically and experimentally, the relative intensity noise (RIN)
      and timing jitter characteristics of optical parametric generation (OPG) process
      in MgO-doped periodically poled LiNbO3 (MgO:PPLN) pumped by fiber femtosecond
      laser. We directly characterize the RIN, and measure timing jitter spectral
      density of the OPG process based on the balanced optical cross-correlator (BOC)
      technique for the first time as well, which are both in a fairly good agreement
      with numerical simulation. Both the numerical and experimental study reveals that
      OPG can suffer from a smaller intensity fluctuation but a lager temporal jitter
      when it is driven into saturation. Furthermore, we demonstrate that with a 30 mW
      CW diode laser injection seeding the OPG output results in superior noise
      performance compared to the vacuum fluctuations seeded OPG.

PMID- 29041405
TI  - Nanoparticle-doped electrospun fiber random lasers with spatially extended light
      modes.
AB  - Complex assemblies of light-emitting polymer nanofibers with molecular materials
      exhibiting optical gain can lead to important advance to amorphous photonics and
      to random laser science and devices. In disordered mats of nanofibers, multiple
      scattering and waveguiding might interplay to determine localization or spreading
      of optical modes as well as correlation effects. Here we study electrospun fibers
      embedding a lasing fluorene-carbazole-fluorene molecule and doped with titania
      nanoparticles, which exhibit random lasing with sub-nm spectral width and
      threshold of about 9 mJ cm-2 for the absorbed excitation fluence. We focus on the
      spatial and spectral behavior of optical modes in the disordered and non-woven
      networks, finding evidence for the presence of modes with very large spatial
      extent, up to the 100 um-scale. These findings suggest emission coupling into
      integrated nanofiber transmission channels as effective mechanism for enhancing
      spectral selectivity in random lasers and correlations of light modes in the
      complex and disordered material.

PMID- 29041406
TI  - Optical fabrication and characterisation of SU-8 disk photonic waveguide
      heterostructure cavities.
AB  - In order to demonstrate cavity quantum electrodynamics using photonic crystal
      (PhC) cavities fabricated around self-assembled quantum dots (QDs), reliable
      spectral and spatial overlap between the cavity mode and the quantum dot is
      required. We present a method for using photoresist to optically fabricate
      heterostructure cavities in a PhC waveguide with a combined photolithography and
      micro-photoluminescence spectroscopy system. The system can identify single QDs
      with a spatial precision of +/-25 nm, and we confirm the creation of high quality
      factor cavity modes deterministically placed with the same spatial precision.
      This method offers a promising route towards bright, on-chip single photon
      sources for quantum information applications.

PMID- 29041407
TI  - Active control of optical chirality with graphene-based achiral nanorings.
AB  - A strong chiral near-field is crucial for the detection of chiral molecules.
      Active tuning of the chiral near-field can shorten the detection process. In this
      study, a graphene-based achiral nanoring (GAN) that can actively control chiral
      near-fields is presented. The GAN is composed of three identical graphene pieces.
      The handedness and strength of the chiral near-fields can be actively controlled
      by adjusting the Fermi levels of these three graphene pieces. The optical
      chirality of the GAN near-field is 500 times that of circularly polarized light.
      In addition, the GAN enhances the chiral response of the chiral material by a
      factor of 250. This work provides opportunities for the ultrasensitive detection
      and location of molecules through the active control of chiral near-fields.

PMID- 29041408
TI  - PAPR reduction based on tone reservation scheme for DCO-OFDM indoor visible light
      communications.
AB  - High peak-to-average power ratio (PAPR) leads to out-of-band power and in-band
      distortion in the direct current-biased optical orthogonal frequency division
      multiplexing (DCO-OFDM) systems. In order to effectively reduce the PAPR with
      faster convergence and lower complexity, this paper proposes a tone reservation
      based scheme, which is the combination of the signal-to-clipping noise ratio
      (SCR) procedure and the least squares approximation (LSA) procedure. In the
      proposed scheme, the transmitter of the DCO-OFDM indoor visible light
      communication (VLC) system is designed to transform the PAPR reduced signal into
      real-valued positive OFDM signal without doubling the transmission bandwidth.
      Moreover, the communication distance and the light emitting diode (LED)
      irradiance angle are taking into consideration in the evaluation of the system
      bit error rate (BER). The PAPR reduction efficiency of the proposed scheme is
      remarkable for DCO-OFDM indoor VLC systems.

PMID- 29041409
TI  - High frequency optomechanical disk resonators in III-V ternary semiconductors.
AB  - Optomechanical systems based on nanophotonics are advancing the field of
      precision motion measurement, quantum control and nanomechanical sensing. In this
      context III-V semiconductors offer original assets like the heteroepitaxial
      growth of optimized metamaterials for photon/phonon interactions. GaAs has
      already demonstrated high performances in optomechanics but suffers from two
      photon absorption (TPA) at the telecom wavelength, which can limit the
      cooperativity. Here, we investigate TPA-free III-V semiconductor materials for
      optomechanics applications: GaAs lattice-matched In0.5Ga0.5P and Al0.4Ga0.6As. We
      report on the fabrication and optical characterization of high frequency (500-700
      MHz) optomechanical disks made out of these two materials, demonstrating high
      optical and mechanical Q in ambient conditions. Finally we achieve operating
      these new devices as laser-sustained optomechanical self-oscillators, and draw a
      first comparative study with existing GaAs systems.

PMID- 29041410
TI  - Characterization of a FBG sensor interrogation system based on a mode-locked
      laser scheme.
AB  - This paper is focused on the characterization of a fiber Bragg grating (FBG)
      sensor interrogation system based on a fiber ring laser with a semiconductor
      optical amplifier as the gain medium, and an in-loop electro-optical modulator.
      This system operates as a switchable active (pulsed) mode-locked laser. The
      operation principle of the system is explained theoretically and validated
      experimentally. The ability of the system to interrogate an array of different
      FBGs in wavelength and spatial domain is demonstrated. Simultaneously, the
      influence of several important parameters on the performance of the interrogation
      technique has been investigated. Specifically, the effects of the bandwidth and
      the reflectivity of the FBGs, the SOA gain, and the depth of the intensity
      modulation have been addressed.

PMID- 29041411
TI  - Degenerate critical coupling in all-dielectric metasurface absorbers.
AB  - We develop the theory of all-dielectric absorbers based on temporal coupled mode
      theory (TCMT), with parameters extracted from eigenfrequency simulations. An
      infinite square array of cylindrical resonators embedded in air is investigated,
      and we find that it supports two eigenmodes of opposite symmetry that are each
      responsible for half of the total absorption. The even and odd eigenmodes are
      found to be the hybrid electric (EH111) and hybrid magnetic (HE111) waveguide
      modes of a dielectric wire of circular cross section, respectively. The geometry
      of the cylindrical array is shown to be useful for individual tuning of the
      radiative loss rates of the eigenmodes, thus permitting frequency degeneracy.
      Further, by specifying the resonators' loss tangent, the material loss rate can
      be made to equal the radiative loss rate, thus achieving a state of degenerate
      critical coupling and perfect absorption. Our results are supported by S
      parameter simulations, and agree well with waveguide theory.

PMID- 29041412
TI  - On the extraordinary optical transmission in parallel plate waveguides for non
      TEM modes.
AB  - Extraordinary transmission has been recently measured in a parallel plate
      waveguide (PPWG) through a metal strip with a patterned 1-D periodic array of
      circular holes, the metal strip being embedded inside the PPWG. Wood's anomaly
      and the extraordinary transmission peak (EOT) were detected for transverse
      electric (TE) mode excitation at frequencies higher than those found for TEM mode
      excitation. In this paper we provide an explanation for this frequency shift by
      decomposing the problem of a TE mode impinging on the 1-D array of holes into two
      problems of plane waves impinging obliquely on 2-D periodic arrays of holes. By
      then solving the integral equation for the electric field on the surface of the
      holes, the origin of the frequency shift is proved both mathematically and
      physically in terms of the symmetries present in the system.

PMID- 29041413
TI  - Spin Hall effect of reflected light in dielectric magneto-optical thin film with
      a double-negative metamaterial substrate: erratum.
AB  - An expression error was produced in the text introducing the dynamic matrix of
      the magnetic layer in [Opt. Express25(16), 19117 (2017)10.1364/OE.25.019117].
      What's more, we used two wrong formula numbers in the analysis section of Eq.
      (11) and Eq. (13). Here we correct the errors.

PMID- 29041414
TI  - Pump induced lasing suppression in Yb:Er-doped microlasers.
AB  - A pump source is one of the essential prerequisites in order to achieve lasing in
      a system, and, in most cases, a stronger pump leads to higher laser power at the
      output. However, this behavior may be suppressed if two pump beams are used. In
      this work, we show that lasing around the 1600 nm band can be suppressed
      completely if two pumps, at wavelengths of 980 nm and 1550 nm, are applied
      simultaneously to an Yb:Er-doped microlaser, whereas it can be revived by
      switching one of them off. This phenomenon can be explained by assuming that the
      presence of one pump (980 nm) changes the role of the other pump (1550 nm); more
      specifically, the 1550 nm pump starts to consume the population inversion instead
      of increasing it when the 980 nm pump power exceeds a certain value. As a result,
      the two pump fields lead to a closed-loop transition within the gain medium
      (i.e., the erbium ions). This study unveils an interplay similar to coherence
      effects between different pump pathways, thereby providing a reference for
      designing the laser pump, and may have applications in lasing control.

PMID- 29041415
TI  - Beam hardening correction in polychromatic x-ray grating interferometry.
AB  - The beam hardening is one of the two causes of the fringe shift distortion in
      polychromatic X-ray grating interferometry. Based on the assumption of the
      uniform energy dependence, we developed a novel analytic approach to accurately
      retrieve the monochromatic attenuation function and fringe phase shift from the
      polychromatic measurement. This approach provides a useful tool for precise
      measurement of sample electron density distribution in X-ray grating
      interferometry.

PMID- 29041416
TI  - Simulation investigation of strained black phosphorus photodetector for middle
      infrared range.
AB  - In this paper, we design the uniaxially and biaxially strained black phosphorus
      (BP) photodetectors. Different strains applied in the zigzag or armchair
      direction can effectively tune the direct band gap of 5-layer of BP. The optical
      field intensity is modeled to determine the absorption for the BP layer. The
      strain effect on the band structure of BP is investigated using first-principles
      method based on density functional theory. The cut-off wavelength of strained 5
      layer of BP pin photodetector is extended to middle infrared range with a high
      responsivity of 66.29 A/W, which means that the strained black phosphorus
      photodetector provides a new approach for the middle-infrared range
      optoelectronic devices.

PMID- 29041417
TI  - Highly birefringent V-groove liquid core fiber.
AB  - We report a new efficient light guidance along a liquid core using an open V
      groove. Guiding properties were analyzed using finite element method in terms of
      the single mode guidance condition, and the corresponding modal birefringence. We
      experimentally demonstrated a silica V-groove fiber with an opening angle of 40
      degrees , which was spliced to single mode fibers at both ends. A liquid with the
      refractive index of 1.455 was filled to serve as a core along a maximum length of
      47cm. We confirmed the single mode guidance and birefringence consistent to
      theory, which will enable polarimetric liquid sensing.

PMID- 29041418
TI  - Dual-layer orthogonal fiber Bragg grating mesh based soft sensor for 3
      dimensional shape sensing.
AB  - A soft shape sensor for 3-dimensional object shape measurement is demonstrated.
      The proposed sensor is based on dual-layer fiber Bragg grating arrays with an
      orthogonal mesh structure, which enables multi-point bi-directional shape
      sensing. The 3D shape reconstruction is based on a bi-directional curvature
      measurement at each sensing point, which is achieved through measuring the
      direction and amount of wavelength shift of each off-center embedded FBG. The
      conversion coefficient between the wavelength shift and bending curvatures is
      acquired and is used to convert the change in FBG to the corresponding bending
      curvatures and bending direction. The measurement error on the bending radius of
      each sensing point is about 2.7%. A 3D shape of the object surface is
      reconstructed with the help of a curve fitting method based on the curvature
      information across the whole FBG mesh. This design successfully achieved
      visualized 3D shape sensing, which has great practical value in soft robotics and
      biomedical applications.

PMID- 29041419
TI  - Resolution enhancement method for lensless in-line holographic microscope with
      spatially-extended light source.
AB  - We propose a resolution enhancement method for lensless in-line holographic
      microscope (LIHM) with spatially-extended light source, where the resolution is
      normally deteriorated by the insufficient spatial coherence of the illumination.
      In our LIHM setup, a light-emitting diode (LED), which was a spatially-extended
      light source, directly illuminated the sample, and the in-line hologram were
      recorded by a CMOS imaging sensor located behind the sample. In our holographic
      reconstruction process, the in-line hologram was first deconvoled with a properly
      resized image of the LED illumination area, and then back-propagated with scalar
      diffraction formula to reconstruct the sample image. We studied the hologram
      forming process and showed that the additional deconvolution process besides
      normal scalar diffraction reconstruction in LIHM can effectively enhance the
      imaging resolution. The resolution enhancements capability was calibrated by
      numerical simulations and imaging experiments with the U.S. air force target as
      the sample. We also used our LIHM to image the wing of a green lacewing to
      further demonstrate the capability of our methods for practical imaging
      applications. Our methods provide a way for LIHM to achieve satisfactory
      resolution with less stringent requirement for spatial coherence of the source
      and could reduce the cost for compact imaging system.

PMID- 29041420
TI  - Dynamics of carrier tunneling and recombination in asymmetric coupled InGaN
      multiple quantum wells.
AB  - In this work, dynamics of carrier tunneling and recombination in InGaN-based
      asymmetric coupled multiple quantum wells (AC-MQWs) are systematically studied by
      excitation power-dependent and temperature-dependent photoluminescence (PL)
      measurements. With different pumping wavelengths of 405 and 325 nm, distinctly
      different PL spectral evolutions are observed, which could be well explained by
      the proposed anomalous carrier "reverse tunneling" based on the forbidden 1h->2e
      transitions in the AC-MQWs. The forbidden transitions are identified through the
      well agreement between the measured photo-modulated reflectance (PR) spectrum and
      the calculated interband transition energies. Our results indicate that, by
      ingeniously designing the MQW structure of the InGaN-based optoelectronic
      devices, it is possible to realize a specific interband optical transition which
      is even not allowed by the selection rule, and thereby effectively improve the
      carrier distribution across the QWs through the conventional and/or anomalous
      "reverse" carrier tunneling.

PMID- 29041421
TI  - Dynamic three-dimensional multifocal spots in high numerical-aperture objectives.
AB  - Multifocal spots in high numerical-aperture (NA) objectives has emerged as a
      rapid, parallel, and multi-location method in a multitude of applications.
      However, the typical method used for forming three-dimensional (3D) multifocal
      spots based on iterative algorithms limits the potential applications. We
      demonstrate a non-iterative method using annular subzone phases (ASPs) that are
      composed of many annular subareas in which phase-only distributions with
      different 3D displacements are filled. The dynamic 3D multifocal spots with
      controllable position of each focal spot in the focal volume of the objective are
      created using the ASPs. The experimental results of such dynamic tunable 3D
      multifocal spots offer the possibility of versatile process in laser 3D
      fabrication, optical trapping, and fast focusing scanned microscopic imaging.

PMID- 29041422
TI  - Polyelectrolyte induced controlled assemblies for the backbone of robust and
      brilliant Raman tags.
AB  - Near-field and far-field optical properties of plasmonic materials can be
      tailored by coupling the existing structures. However, fabricating 3D coupled
      structures in the solution by molecular linkers may suffer from low yield, low
      stability (particle aggregates), long reaction time, complex surface modification
      or multiple purification steps. In this report, stable 3D plasmonic core
      satellite assemblies (CSA) with a ~1 nm interior gap accompanied by high field
      enhancement (|E/Einc|>200) are formed in a few seconds through a single
      polyelectrolyte linker layer. In addition, by covalently binding different
      reporter molecules and core particles, three distinct RamSSan tags based on this
      CSA backbone are demonstrated and compared with conventional fluorophores in
      terms of stability. This general assembly method can be applied to any type of
      colloidal particles carrying stable surface charge, even non-plasmonic
      nanoparticles. It will facilitate the development of various robust Raman tags
      for multiplexed biomedical imaging/sensing by efficiently combining constituent
      particles of differing size/shape/composition. The CSA backbone with an embedded
      high field not only makes the brightness of Raman tags more comparable to the
      fluorophores and can also be utilized in the platform of molecule-light quantum
      strong coupling.

PMID- 29041423
TI  - Efficient tensor approach for simulating paraxial propagation of arbitrary
      partially coherent beams.
AB  - Complicated partially coherent beams (PCBs) are useful in many applications, such
      as free-space optical communications, particle trapping and optical imaging,
      while usually it is hard to derive analytical propagation formulae for such
      beams, and one has to fall back on numerical methods. The conventional numerical
      methods have some intrinsic drawbacks. In this paper, we introduce an efficient
      tensor approach (ETA) for simulating paraxial propagation of arbitrary PCBs. The
      ETA is a direct reconstruction of the propagated PCB without aliasing and
      rippling problems, and the algorithm is simple and robust with a tensor/matrix
      multiplication as the main calculation. The validity of ETA is verified through
      comparing simulation results with analytical results, numerical integration
      results and experimental results, respectively. The ETA provides a fast and
      reliable way for simulating paraxial propagation of arbitrary PCBs.

PMID- 29041424
TI  - Experimental comparison of pulse-amplitude and spatial modulations for vehicle-to
      vehicle visible light communication in platoon configurations.
AB  - Visible light communication (VLC) is an attractive complementary communication
      technology for vehicular applications such as platooning. Although data rates
      around 100 kbps are enough for crucial data transmission, it may be useful to
      reach a few megabits per second for other applications like networking. Such data
      rates can be reached by using appropriate modulations and clock rates. In this
      paper, three forms of pulse amplitude modulations (PAM) are compared in a
      vehicular context: on-off keying (OOK), PAM-4 and generalized space-shift keying
      (GSSK). A prototype based on off-the-shelf light-emitting diodes (LED) headlamps
      is used for static tests in straight line configuration, with an inter-vehicle
      distance up to 30 m, and curves of minimum radius 100 m and inter-vehicle
      distance of 10 m. These tests show that OOK and GSSK are the most interesting
      modulations for highway platooning applications. OOK provides indeed a good
      mobility while remaining simple to implement. A 1 Mbps link of BER below 10-6 is
      thus demonstrated. In GSSK, the data rate reaches 2 Mbps for an equivalent BER.
      These performances are obtained by using, in particular, two spatially distinct
      receivers, which limits strongly the complexity of GSSK decoding.

PMID- 29041425
TI  - Full-spectrum light management by pseudo-disordered moth-eye structures for thin
      film solar cells: erratum.
AB  - This erratum is presented to correct Fig. 11 in [Opt. Express25(16), A824
      (2017)].

PMID- 29041426
TI  - Spectroscopic characteristics, continuous-wave and mode-locking laser
      performances of Tm,Y:CaF2 disordered crystal.
AB  - The spectroscopic characteristics, continuous-wave (CW) and mode-locking laser
      performances of Tm,Y:CaF2 disordered crystal were studied. A maximum CW output
      power of 586 mW was obtained with a slope efficiency of 26%. The Tm,Y:CaF2 mode
      locked laser could operate in two states: single-wavelength mode locking or dual
      wavelength synchronous mode locking. The single-wavelength mode-locked laser
      generated pulses with pulse duration of 22 ps, repetition rate of 99 MHz, and
      pulse energy of 1.15 nJ at 1887 nm. Alternatively, the laser could also be mode
      locked simultaneously at 1880.7 nm and 1889.0 nm wavelengths. The beating
      modulation in autocorrelation trace shows that the dual-wavelength pulses were
      temporally synchronous.

PMID- 29041427
TI  - Programmable dispersion on a photonic integrated circuit for classical and
      quantum applications.
AB  - We demonstrate a large-scale tunable-coupling ring resonator array, suitable for
      high-dimensional classical and quantum transforms, in a CMOS-compatible silicon
      photonics platform. The device consists of a waveguide coupled to 15 ring-based
      dispersive elements with programmable linewidths and resonance frequencies. The
      ability to control both quality factor and frequency of each ring provides an
      unprecedented 30 degrees of freedom in dispersion control on a single spatial
      channel. This programmable dispersion control system has a range of applications,
      including mode-locked lasers, quantum key distribution, and photon-pair
      generation. We also propose a novel application enabled by this circuit - high
      speed quantum communications using temporal-mode-based quantum data locking - and
      discuss the utility of the system for performing the high-dimensional unitary
      optical transformations necessary for a quantum data locking demonstration.

PMID- 29041428
TI  - Enhanced direct-gap light emission from Si-capped n+-Ge epitaxial layers on Si
      after post-growth rapid cyclic annealing: impact of non-radiative interface
      recombination toward Ge/Si double heterostructure lasers.
AB  - Enhanced direct-gap light emission is reported for Si-capped n+-Ge layers on Si
      after post-growth rapid cyclic annealing (RCA), and impact of non-radiative
      recombination (NRR) at the Ge/Si interface is discussed toward Ge/Si double
      heterostructure (DH) lasers. P-doped n+-Ge layer (1 * 1019 cm-3, 400 nm) is grown
      on Si by ultra-high vacuum chemical vapor deposition, followed by a growth of Si
      capping layer (5 nm) to form a Si/Ge/Si DH structure. Post-growth RCA to
      eliminate defects in Ge is performed in N2 at temperatures between 900 degrees C
      and 780 degrees C, where the annealing time is minimized to be 5 s in each RCA
      cycle to prevent an out-diffusion of P dopants from the Ge surface. Direct-gap
      photoluminescence (PL) intensity at 1.6 um increases with the RCA cycles up to
      40, although the threading dislocation density in Ge is not reduced after 3
      cycles in the present condition. The PL enhancement is ascribed to the
      suppression of NRR at the Ge/Si interface, where an intermixed SiGe alloy is
      formed. For Ge/Si DH lasers, NRR at the Ge/Si interface is found to have a
      significant impact on the threshold current density Jth. In order to achieve Jth
      on the order of 1 kA/cm2, similar to III-V lasers, the interface recombination
      velocity S is required below 103 cm/s in spite of S as large as 105 cm/s at the
      ordinary defect-rich Ge/Si interface.

PMID- 29041429
TI  - Improved measurement of two-mode quantum correlations using a phase-sensitive
      amplifier.
AB  - We demonstrate the ability of a phase-sensitive amplifier (PSA) to pre-amplify a
      selected quadrature of one mode of a two-mode squeezed state in order to improve
      the measurement of two-mode quantum correlations that exist before degradation
      due to optical and detection losses. We use four-wave mixing (4WM) in 85Rb vapor
      to generate bright beams in a two-mode squeezed state. One of these two modes
      then passes through a second 4WM interaction in a PSA configuration to
      noiselessly pre-amplify the desired quadrature of the mode before loss is
      intentionally introduced. We demonstrate an enhancement in the measured degree of
      intensity correlation and intensity-difference squeezing between the two modes.

PMID- 29041430
TI  - Femtosecond-level timing fluctuation suppression in atmospheric frequency
      transfer with passive phase conjunction correction.
AB  - We demonstrate femtosecond-level timing fluctuation suppression in indoor
      atmospheric comb-based frequency transfer with a passive phase conjunction
      correction technique. Timing fluctuations and Allan deviations are both measured
      to characterize the excess frequency instability incurred during the frequency
      transfer process. By transferring a 2 GHz microwave over a 52-m long free-space
      link in 5000 s, the total root-mean-square (RMS) timing fluctuation was measured
      to be about 280 fs with a fractional frequency instability on the order of 3 * 10
      13 at 1 s and 6 * 10-17 at 1000 s. This atmospheric comb-based frequency transfer
      with passive phase conjunction correction can be used to build an atomic clock
      based free-space frequency transmission link because its instability is less than
      that of a commercial Cs or H-master clock.

PMID- 29041431
TI  - Depth resolved snapshot energy-dispersive X-ray diffraction using a conical shell
      beam.
AB  - We demonstrate a novel imaging architecture to collect range encoded diffraction
      patterns from overlapping samples in a single conical shell projection. The
      patterns were measured in the dark area encompassed by the beam via a centrally
      positioned aperture optically coupled to a pixelated energy-resolving detector.
      We show that a single exposure measurement of 0.3 mAs enables d-spacing values to
      be calculated. The axial positions of the samples were not required and the
      resultant measurements were robust in the presence of crystallographic textures.
      Our results demonstrate rapid volumetric materials characterization and the
      potential for a direct imaging method, which is of great relevance to
      applications in medicine, non-destructive testing and security screening.

PMID- 29041432
TI  - Self-focusing effect of annular beams propagating in the atmosphere.
AB  - The self-focusing effect of annular beams propagating in the atmosphere to assist
      delivering powerful laser beams from orbit to the ground is studied in detail. It
      is found the annular beam is compressed more strongly due to the self-focusing
      effect as the beam obscure ratio increases. On the other hand, the self-focusing
      effect between annular, flat-topped and Gaussian beams is compared. It is shown
      that the self-focusing effect on the annular beam is stronger than that on flat
      topped and Gaussian beams. However, the threshold critical power values of
      annular, flat-topped and Gaussian beams should be in sequence from small to
      large. Furthermore, the expression of the B integral of annular beams propagating
      from orbit to the ground in the atmosphere is derived, and the fitting equation
      related to the B integral of annular beams for maximal compression without
      filamentation is presented.

PMID- 29041433
TI  - Second harmonic generation enhancement from a nonlinear nanocrystal integrated
      hyperbolic metamaterial cavity.
AB  - We theoretically investigate the dipolar whispering-gallery modes (WGMs) with
      different mode orders supported by spherical hyperbolic metamaterial (HMM)
      cavities consisting of alternating metal and dielectric layers. Associated with
      the excitations of the WGMs with the highest and the second highest mode orders,
      the HMM cavities are capable of creating highly enhanced and uniformly
      distributed local fields in the entire dielectric core region. Variation on the
      metal filling ratio allows for easily tuning the resonant wavelengths of WGMs
      over a wide spectral range. By integrating a nonlinear nanocrystal into the HMM
      cavities, we show enhancements of intensity of second harmonic generation up to a
      factor of 3.9 * 1010, which is two orders of magnitude higher than the largest
      enhancement achieved in the single-layer plasmonic core-shell cavities.

PMID- 29041434
TI  - Thermal analysis and laser performance of a GYSGG/Cr,Er,Pr:GYSGG composite laser
      crystal operated at 2.79 MUm.
AB  - We demonstrate the thermal analysis and laser performance of a
      GYSGG/Cr,Er,Pr:GYSGG composite crystal. The lifetime ratio of lower and upper
      levels of Er3+ in Cr,Er,Pr:GYSGG crystal is further reduced due to the optimized
      doping concentrations. The thermal effect of composite crystal is lower than that
      of Cr,Er,Pr:GYSGG crystal. A maximum pulse energy 342.8 mJ operated at 5 Hz and
      2.79 MUm is obtained on the composite crystal, corresponding to electrical-to
      optical efficiency of 0.86% and slope efficiency of 1.08%. Under the same
      condition, these values on the Cr,Er,Pr:GYSGG crystal are only 315.8 mJ, 0.79%
      and 1.04%, respectively. Moreover, the composite crystal has also a relative high
      laser beam quality, exhibiting obvious advantage in reducing thermal effects and
      improving laser performances.

PMID- 29041435
TI  - General point dipole theory for periodic metasurfaces: magnetoelectric scattering
      lattices coupled to planar photonic structures.
AB  - We study semi-analytically the light emission and absorption properties of
      arbitrary stratified photonic structures with embedded two-dimensional
      magnetoelectric point scattering lattices, as used in recent plasmon-enhanced
      LEDs and solar cells. By employing dyadic Green's function for the layered
      structure in combination with the Ewald lattice summation to deal with the
      particle lattice, we develop an efficient method to study the coupling between
      planar 2D scattering lattices of plasmonic, or metamaterial point particles,
      coupled to layered structures. Using the 'array scanning method' we deal with
      localized sources. Firstly, we apply our method to light emission enhancement of
      dipole emitters in slab waveguides, mediated by plasmonic lattices. We benchmark
      the array scanning method against a reciprocity-based approach to find that the
      calculated radiative rate enhancement in k-space below the light cone shows
      excellent agreement. Secondly, we apply our method to study absorption
      enhancement in thin-film solar cells mediated by periodic Ag nanoparticle arrays.
      Lastly, we study the emission distribution in k-space of a coupled waveguide
      lattice system. In particular, we explore the dark mode excitation on the
      plasmonic lattice using the so-called array scanning method. Our method could be
      useful for simulating a broad range of complex nanophotonic structures, i.e.,
      metasurfaces, plasmon-enhanced light emitting systems and photovoltaics.

PMID- 29041436
TI  - Self-injection locked CW single-frequency tunable Ti:sapphire laser.
AB  - A self-injection locked continuous-wave (CW) single-frequency tunable Ti:sapphire
      laser is demonstrated in this paper. Unidirectional operation of the presented
      Ti:sapphire laser is achieved by using a retro-reflecting device which can retro
      reflect a seed laser beam from one direction back into the counter-propagating
      field. On the basis, the influence of the transmission of output coupler on the
      unidirectional operation is investigated and it is found that stable
      unidirectional and single-frequency operation of the Ti:sapphire laser is
      achieved when the loss difference between both output directions is larger than a
      certain value, which is easy to be realized by choosing the transmission of
      output coupler. When the output coupler with transmission of 6.5% is utilized,
      the maximal 5 W CW single-frequency Ti:sapphire laser with stable unidirectional
      operation is obtained with the pump power of 18 W. The measured power stability
      and M2 are better than +/-0.9% and 1.1, respectively. The maximal tuning range
      and continuous frequency-tuning ability are 120 nm and 40.75 GHz, respectively.

PMID- 29041437
TI  - Single-frequency oscillation of thin-disk lasers due to phase-matched pumping.
AB  - We present a novel pump concept that should lead to single-frequency operation of
      thin-disk lasers without the need for etalons or other spectral filters. The
      single-frequency operation is due to matching the standing wave pattern of
      partially coherent pump light to the standing wave pattern of the laser light
      inside the disk. The output power and the optical efficiency of our novel pump
      concept are compared with conventional pumping. The feasibility of our pump
      concept was shown in previous experiments.

PMID- 29041438
TI  - Widely tunable semiconductor lasers with three interferometric arms.
AB  - We present a comprehensive study for a new three-branch widely tunable
      semiconductor laser based on a self-imaging, lossless multi-mode interference
      (MMI) coupler. We have developed a general theoretical framework that is
      applicable to all types of interferometric lasers. Our analysis showed that the
      three-branch laser offers high side-mode suppression ratios (SMSRs) while
      maintaining a wide tuning range and a low threshold modal gain of the lasing
      mode. We also present the design rules for tuning over the dense-wavelength
      division multiplexing grid over the C-band.

PMID- 29041439
TI  - Equivalence theorem of light waves on scattering from media with different types.
AB  - The equivalence theorem of light waves on scattering from two media with
      different types, i.e. the continuous medium and the particulate medium, is
      discussed. It is shown that the normalized spectral density or the spectral
      degree of coherence of the scattered field may demonstrate identical distribution
      when certain conditions between these two media are satisfied. As an example, the
      scattering of light waves from a Gaussian-centered quasi-homogeneous medium and
      from a collection of particles with Gaussian-centered quasi-homogeneous
      distribution is investigated, and the condition for identical normalized spectral
      density and the condition for identical spectral degree of coherence of the
      scattered field are obtained.

PMID- 29041440
TI  - Dispersion controlling meta-lens at visible frequency.
AB  - Dispersion management is crucial in constructing spectrometers, superprisms, and
      achromatic lens systems. Unfortunately, the dispersion of natural materials is
      determined by the molecular energy levels with limited tunability, and thus
      conventional methods of dispersion controlling are complex and need to trade off
      other aberration. Metasurface offers an alternative method to overcome those
      limits via utilizing dedicatedly designed nanostructures that response to special
      wavelength, which results in well-engineered dispersions. As proof of the
      concept, we design a series of flat dielectric metasurface lenses, which are able
      to steer the dispersion arbitrarily for three wavelengths at visible frequency
      (473, 532, and 632.8 nm). Based on the unique dispersion engineering ability of
      metasurface, the achromatic meta-lens and the super-dispersion meta-lenses are
      realized. Furthermore, the light of different wavelengths can be focused on any
      desired spatial positions.

PMID- 29041441
TI  - Impact of carbon-ion implantation on the nonlinear optical susceptibility of
      LiNbO3.
AB  - In this work we study the impact of ion implantation on the nonlinear optical
      properties in MgO:LiNbO3 via confocal second-harmonic microscopy. In detail, we
      spatially characterize the nonlinear susceptibility in carbon-ion implanted
      lithium niobate planar waveguides for different implantation energies and
      fluences, as well as the effect of annealing. In a further step, a computational
      simulation is used to calculate the implantation range of carbon-ions and the
      corresponding defect density distribution. A comparison between the simulation
      and the experimental data indicates that the depth profile of the second-order
      effective nonlinear coefficient is directly connected to the defect density that
      is induced by the ion irradiation. Furthermore it can be demonstrated that the
      annealing treatment partially recovers the second-order optical susceptibility.

PMID- 29041442
TI  - Performance optimization in ultra-long Raman laser amplified 10*30 GBaud DP-QPSK
      transmission: balancing RIN and ASE noise.
AB  - We experimentally evaluate the influence of RIN transfer from pump to signal on
      the transmission performance of a 10 * 30 Gbaud DP-QPSK transmission system using
      a 2nd-order ultra-long Raman fiber laser amplifier, considering the effect of
      cavity front-end reflectivity and forward pump power ratio. The evolution of the
      Q-factors with distance up to maximum reach is monitored for a 10 * 30 Gbaud DP
      QPSK transmission system with WDM channels between 1542.94 nm to 1550.12 nm. A
      maximum transmission distance of 6479 km is found for configurations with low
      forward pump powers corresponding to the optimal balance between RIN and ASE
      impairments.

PMID- 29041443
TI  - Generation of the periodically polarized structured light beams.
AB  - We report a kind of structured light beam with periodical polarization and phase
      singularities. It is generated from a setup consisting of conical refraction
      transformation and 4f-system. By this setup, the periodical structures are
      produced without any change of intensity distributions. We analyze both
      theoretically and experimentally the polarization and phase structures of the
      periodically structured light beam. The dependence of period is demonstrated on
      the length of crystal and the focal length. It is shown that the polarization of
      the input beam can be used to control the polarization and phase structures of
      the output beam.

PMID- 29041444
TI  - Vortex topographic microscopy for full-field reference-free imaging and testing.
AB  - Light vortices carry orbital angular momentum and have a variety of applications
      in optical manipulation, high-capacity communications or microscopy. Here we
      propose a new concept of full-field vortex topographic microscopy enabling a
      reference-free displacement and shape measurement of reflective samples. The
      sample surface is mapped by an array of light spots enabling quantitative
      reconstruction of the local depths from defocused wavefronts. Light from the
      spots is converted to a lattice of mutually uncorrelated double-helix point
      spread functions (PSFs) whose angular rotation enables depth estimation. The PSFs
      are created by self-interference of optical vortices that originate from the same
      wavefront and are shaped by a spiral phase mask (SPM). The method benefits from
      the isoplanatic PSFs whose shape and size remain unchanged under defocusing,
      ensuring high precision in a wide range of measured depths. The technique was
      tested using a microscope Nikon Eclipse E600 working with a micro-hole plate
      providing structured illumination and the SPM placed in the imaging path. The
      depth measurement was demonstrated in the range of 11 um exceeding the depth of
      field of the microscope objective up to 19 times. Throughout this range, the
      surface depth was mapped with the precision better than 30 nm at the lateral
      positions given with the precision better than 10 nm. Application potential of
      the method was demonstrated by profiling the top surface of a bearing ball and
      reconstructing the three-dimensional relief of a reflection phase grating.

PMID- 29041445
TI  - Athermal silicon optical add-drop multiplexers based on thermo-optic coefficient
      tuning of sol-gel material.
AB  - Silicon photonics has gained interest for its potential to provide higher
      efficiency, bandwidth and reduced power consumption compared to electrical
      interconnects in datacenters and high performance computing environments.
      However, it is well known that silicon photonic devices suffer from temperature
      fluctuations due to silicon's high thermo-optic coefficient and therefore,
      temperature control in many applications is required. Here we present an athermal
      optical add-drop multiplexer fabricated from ring resonators. We used a sol-gel
      inorganic-organic hybrid material as an alternative to previously used materials
      such as polymers and titanium dioxide. In this work we studied the thermal curing
      parameters of the sol-gel and their effect on thermal wavelength shift of the
      rings. With this method, we were able to demonstrate a thermal shift down to -6.8
      pm/ degrees C for transverse electric (TE) polarization in ring resonators with
      waveguide widths of 325 nm when the sol-gel was cured at 130 degrees C for 10.5
      hours. We also achieved thermal shifts below 1 pm/ degrees C for transverse
      magnetic (TM) polarization in the C band under different curing conditions.
      Curing time compared to curing temperature shows to be the most important factor
      to control sol-gel's thermo-optic value in order to obtain an athermal device in
      a wide temperature range.

PMID- 29041446
TI  - Verification of calibration methods for determining photon-counting detection
      efficiency using superconducting nano-wire single photon detectors.
AB  - In recent years several ways to radiometrically calibrate optical fiber-coupled
      detectors have been developed. However, fiber-coupled calibration methods for
      single photon detectors have not been compared by national metrology institutes
      in order to validate their equivalence or traceability to the international
      systems of units yet.. Here, we present the comparison of radiometric calibration
      methods traceable to a NIST cryogenic radiometer at the 'few-photon' level. The
      calibration methods are based on metrology grade optical power meters. The
      expanded (k = 2) relative standard uncertainties of the calibration methods for
      the detection efficiency are of the order of 0.5%. However, the results changed
      relatively by 10% with a different set of optical fibers and mating connectors.
      These results stress the importance of fiber-core dimensions and fiber-connector
      repeatability.

PMID- 29041447
TI  - Characterization, uniformity and photo-catalytic properties of graphene/TiO2
      nanocomposites via Raman mapping.
AB  - Three types of anatase TiO2, graphene-TiO2, TiO2-graphene composites (G/TiO2)
      were developed, synthesized via a combination of simple sol-gel self-assembly
      method and additional thermal annealing process. Their structures and properties
      are determined by scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), X-ray diffraction (XRD), atomic force microscopy (AFM) and
      Raman spectrum analysis. In addition, Raman spectra of TiO2 and graphene, the
      band shift and intensity of G and 2D band were analyzed, in order to verify the
      mutual coupling between TiO2 and graphene. Combined Raman mapping with AFM
      analysis, the agglomeration effect of TiO2 nanoparticles was figured out by
      quantitative analysis. Finally, the photo-catalytic properties of three kinds of
      composites were experimentally studied via Raman mapping measurements. The
      results reveal that graphene with high electron mobility, as an acceptor through
      interfacial interactions, was certificated to enhance the photo-catalytic effect
      of TiO2.

PMID- 29041448
TI  - Security weaknesses of underwater wireless optical communication.
AB  - In this work, for the first time, we uncover that the level of security we have
      traditionally taken for granted on underwater wireless optical communication
      (UWOC) may not always be there. We first numerically investigate the security
      weaknesses of UWOC via Monte Carlo simulation. With the link distance increasing
      or the water becoming more turbid, the simulation results indicate that the
      possibility of information leakage increases, which may pose a great threat to
      the security of UWOC. By using a high-sensitivity multi-pixel photon counter
      (MPPC) placed aside the water tank, a 5-MHz square wave signal is successfully
      tapped at 1-m, 3-m, and 5-m underwater transmission distances, which
      preliminarily verifies the probability of information leakage. We further
      experimentally demonstrate an UWOC system with potential eavesdropping employing
      a 2.5-Gb/s orthogonal frequency division multiplexing (OFDM) signal. After
      transmitting through a 15-m underwater channel, the OFDM signal is eavesdropped
      by a mirror at 7.8 m. Both the normal receiver at 15 m and the eavesdropping
      receiver at 7.8 m can achieve a bit error rate (BER) below the forward error
      correction (FEC) limit of 3.8 * 10-3, which validates that UWOC indeed suffers
      potential safety hazard.

PMID- 29041449
TI  - Low-threshold, single-mode, and linearly polarized lasing from all organic
      quasicrystal microcavity.
AB  - Organic microcavity lasers based on liquid crystals have attracted substantial
      attention due to their easy processing, compact volume and excellent tunable
      properties. However, the threshold of traditional holographic polymer dispersed
      liquid crystals (H-PDLCs) laser doped with dye is usually as high as several tens
      of MUJ/pulse, which hinders its broad applications. Herein, we demonstrate a low
      threshold lasing from quasicrystal based on H-PDLCs. An conjugated polymer poly
      (2-methoxy-5-(2'-ethyl-hexyloxy)-p-phenylenevinylene (MEH-PPV) film is coated on
      the inner surface of glass substrate to dramatically reduce the lasing threshold,
      which is 20 times lower than that of dye-doped microcavity laser. A low
      threshold, single-mode, linearly polarized lasing is achieved when the thickness
      of MEH-PPV film is optimized at 80 nm. Due to its easy fabrication, excellent
      performance and bio-compatibility, this compact coherent light source may be
      useful in lab-on-chip applications such as detection, sensing and analyzing, as
      well as display, optical communications, and other photonic fields.

PMID- 29041450
TI  - Dependencies of surface plasmon coupling effects on the p-GaN thickness of a thin
      p-type light-emitting diode.
AB  - The high performance of a light-emitting diode (LED) with the total p-type
      thickness as small as 38 nm is demonstrated. By increasing the Mg doping
      concentration in the p-AlGaN electron blocking layer through an Mg pre-flow
      process, the hole injection efficiency can be significantly enhanced. Based on
      this technique, the high LED performance can be maintained when the p-type layer
      thickness is significantly reduced. Then, the surface plasmon coupling effects,
      including the enhancement of internal quantum efficiency, increase in output
      intensity, reduction of efficiency droop, and increase of modulation bandwidth,
      among the thin p-type LED samples of different p-type thicknesses that are
      compared. These advantageous effects are stronger as the p-type layer becomes
      thinner. However, the dependencies of these effects on p-type layer thickness are
      different. With a circular mesa size of 10 MUm in radius, through surface plasmon
      coupling, we achieve the record-high modulation bandwidth of 625.6 MHz among c
      plane GaN-based LEDs.

PMID- 29041451
TI  - Experimental demonstration of optical interconnects exploiting orbital angular
      momentum array.
AB  - To improve the transmission capacity and integration level of future optical
      interconnect systems, we present a communication scheme using orbital angular
      momentum (OAM) array encoding/decoding. By optimizing the use of space dimension
      (spatially orthogonal modes and spatial positions), information carried by a
      single symbol can be greatly improved. Experiment demonstration of 625-element
      and 1296-element high-base OAM array encoding/decoding by employing an array with
      4 spatial locations each with 5 and 6 possible OAM beams are presented. Direct
      detection and simultaneous multi-OAM demodulation method are used for decoding
      the encoded OAM arrays. Transmission of data signal and grey-scale image signal
      under atmospheric turbulence are also evaluated in the experiment.

PMID- 29041452
TI  - In situ high-resolution thermal microscopy on integrated circuits.
AB  - The miniaturization of metal tracks in integrated circuits (ICs) can cause
      abnormal heat dissipation, resulting in electrostatic discharge, overvoltage
      breakdown, and other unwanted issues. Unfortunately, locating areas of abnormal
      heat dissipation is limited either by the spatial resolution or imaging
      acquisition speed of current thermal analytical techniques. A rapid, non-contact
      approach to the thermal imaging of ICs with sub-MUm resolution could help to
      alleviate this issue. In this work, based on the intensity of the temperature
      dependent two-photon fluorescence (TPF) of Rhodamine 6G (R6G) material, we
      developed a novel fast and non-invasive thermal microscopy with a sub-MUm
      resolution. Its application to the location of hotspots that may evolve into
      thermally induced defects in ICs was also demonstrated. To the best of our
      knowledge, this is the first study to present high-resolution 2D thermal
      microscopic images of ICs, showing the generation, propagation, and distribution
      of heat during its operation. According to the demonstrated results, this scheme
      has considerable potential for future in situ hotspot analysis during the
      optimization stage of IC development.

PMID- 29041453
TI  - Sensitivity enhanced fiber sensor based on a fiber ring microwave photonic filter
      with the Vernier effect.
AB  - A temperature sensor employing the Vernier effect generated from a cascaded fiber
      rings based microwave photonic filter (MPF) is proposed and experimentally
      demonstrated. The structure of the fiber ring is used as a sensing element as
      well as the sampling and delaying component of the MPF in our proposed sensing
      scheme. The sensing characteristics of both single ring and cascaded fiber rings
      based sensors have been studied and compared. By employing two cascaded fiber
      rings of slightly different length, the Vernier effect can be generated in the
      frequency response of the MPF. The sensing interrogation of the cascaded fiber
      rings based sensor is conducted by detecting the frequency shift of the upper
      envelope of the measured frequency response curve. The experimental results show
      that the sensitivity of the cascaded fiber rings based sensor can be improved
      about 30 times compared with the single fiber ring based temperature sensor.

PMID- 29041454
TI  - Self-calibration of Fizeau interferometer and planar scale gratings in Littrow
      setup.
AB  - A new method, in which the wavefronts of the zero-order and the positive and
      negative first-order diffracted beams from a planar scale grating in Littrow
      setup are analyzed by a Fizeau interferometer, is proposed to evaluate the Z
      directional out-of-flatness as well as the X- and Y-directional pitch deviations
      of the planar scale grating over a large area. Meanwhile, the surface profile of
      the reference optical flat in the Fizeau interferometer can also be determined in
      a much simpler and more efficient approach than the commonly used liquid-flat
      reference and three-flat test calibration methods. Simulations are presented to
      verify the feasibility of the proposed method.

PMID- 29041455
TI  - Ultra-bright gamma-ray flashes and dense attosecond positron bunches from two
      counter-propagating laser pulses irradiating a micro-wire target.
AB  - We propose a novel scheme to generate ultra-bright ultra-short gamma-ray flashes
      and high-energy-density attosecond positron bunches by using multi-dimensional
      particle-in-cell simulations with quantum electrodynamics effects incorporated.
      By irradiating a 10 PW laser pulse with an intensity of 1023 W/cm2 onto a micro
      wire target, surface electrons are dragged-out of the micro-wire and are
      effectively accelerated to several GeV energies by the laser ponderomotive force,
      forming relativistic attosecond electron bunches. When these electrons interact
      with the probe pulse from the other side, ultra-short gamma-ray flashes are
      emitted with an ultra-high peak brightness of 1.8 * 1024 photons s-1mm-2mrad-2
      per 0.1%BW at 24 MeV. These photons propagate with a low divergence and collide
      with the probe pulse, triggering the Breit-Wheeler process. Dense attosecond e-e+
      pair bunches are produced with the positron energy density as high as 1017 J/m3
      and number of 109. Such ultra-bright ultra-short gamma-ray flashes and secondary
      positron beams may have potential applications in fundamental physics, high
      energy-density physics, applied science and laboratory astrophysics.

PMID- 29041456
TI  - Cylindrical vector resonant modes achieved in planar photonic crystal cavities
      with enlarged air-holes.
AB  - We reveal a triangular-lattice planar photonic crystal supports Bloch modes with
      radially and azimuthally symmetric electric field distributions at the top band
      edge of the first photonic band. Bifurcated from the corresponding Bloch modes,
      two cylindrical vector resonant modes are achieved by simply enlarging the
      central air-hole of the planar photonic crystal, which have high quality factors
      around 3,000 and small mode volume of (lambda/n)3. The far-field radiations of
      the two resonant modes present high-quality cylindrical vector beam profiles. The
      resonant modes could be optimized by modifying the six nearest neighboring air
      holes around the central defect. The cylindrically symmetric characteristics of
      the resonant mode's near- and far-fields might provide a new view to investigate
      light-matter interactions and device developments in planar photonic crystal
      cavities.

PMID- 29041457
TI  - Adaptively loaded SP-offset-QAM OFDM for IM/DD communication systems.
AB  - In this paper, we propose adaptively loaded set-partitioned offset quadrature
      amplitude modulation (SP-offset-QAM) orthogonal frequency division multiplexing
      (OFDM) for low-cost intensity-modulation direct-detection (IM/DD) communication
      systems. We compare this scheme with multi-band carrier-less amplitude phase
      modulation (CAP) and conventional OFDM, and demonstrate >40 Gbit/s transmission
      over 50-km single-mode fiber. It is shown that the use of SP-QAM formats,
      together with the adaptive loading algorithm specifically designed to this group
      of formats, results in significant performance improvement for all these three
      schemes. SP-offset-QAM OFDM exhibits greatly reduced complexity compared to SP
      QAM based multi-band CAP, via parallelized implementation and minimized memory
      length for spectral shaping. On the other hand, this scheme shows better
      performance than SP-QAM based conventional OFDM at both back-to-back and after
      transmission. We also characterize the proposed scheme in terms of enhanced
      tolerance to fiber intra-channel nonlinearity and the potential to increase the
      communication security. The studies show that adaptive SP-offset-QAM OFDM is a
      promising IM/DD solution for medium- and long-reach optical access networks and
      data center connections.

PMID- 29041458
TI  - Multilayer graphene electro-absorption optical modulator based on double-stripe
      silicon nitride waveguide.
AB  - A graphene electro-absorption optical modulator based on double-stripe silicon
      nitride waveguide is proposed and analyzed. By embedding four graphene layers in
      the double-stripe silicon nitride waveguide and the graphene layers co-electrode
      design, the total metal-graphene contact resistance can be reduced 50% and as
      high as 30.6GHz modulation bandwidth can be achieved theoretically. The
      calculated extinction ratio and figure of merit are 0.1658dB/um and 9.7,
      respectively. And the required switching voltage from its minimum to maximum
      absorption state is 3.8180V and 780.50fJ/bit power consuming can be achieved. The
      proposed modulator can remedy the lack of high speed modulator on the passive
      silicon nitride waveguide.

PMID- 29041459
TI  - Nearly perfect absorption of light in monolayer molybdenum disulfide supported by
      multilayer structures.
AB  - A novel multilayer photonic structure is proposed to achieve the strong
      enhancement of light absorption in monolayer molybdenum disulfide (MoS2). Both
      numerical and analytical results illustrate that the absolute absorption of light
      in this atomically thin layer can approach as high as 96% at the visible
      wavelengths due to the excitation of Tamm plasmon mode. It is also found that the
      operating wavelength and height of sharp absorption peak are particularly
      dependent on the layer thicknesses and period number of dielectric grating, MoS2
      position in the spacer, and incident angle of light, which contribute to the
      tunability and selectivity of light-MoS2 interaction. These results would provide
      a new pathway for the improvement of MoS2 photoluminescence and photodetection.

PMID- 29041460
TI  - Optimizing the spectral range of diffractive metalenses for polychromatic imaging
      applications.
AB  - Recent progress has made matalenses a reality, with many publications relating to
      methods of implementation and performance evaluation of these elements. Basic
      metalens function is similar to that of a continuous (kinoform) diffractive lens,
      but the advantage is that they can be manufactured as a binary component. A
      significant limitation of metalenses, is its strong chromatic aberration.
      Recently there has been some success in correcting metalens chromatic aberration,
      albeit at the expense of transmission efficiency towards the desired diffraction
      order. Clearly, there is a tradeoff between parameters such as spectral bandwidth
      and spatial resolution. Hence, a major goal of this paper is to set up a metric
      for evaluation of metalens performance, allowing fair comparison of novel
      metalens technologies, such as achromatic metalenses, in terms of optical
      performance. Furthermore, we explore possibilities for practical use of non
      chromatically corrected metalenses in polychromatic applications, by optimizing
      the metalens parameters. It is our hope that the current manuscript will serve as
      a guide for the design and evaluation of metalenses for practical applications.

PMID- 29041462
TI  - Phase retrieval in two-shot phase-shifting interferometry based on phase shift
      estimation in a local mask.
AB  - Fringe analysis in two-shot phase-shifting interferometry is important but meets
      challenges due to a limited number of images, corrupting noise, and background
      modulation. Here we propose an effective algorithm for phase retrieval from two
      interferograms with unknown phase shifts. The algorithm first evaluates the phase
      shift in a local mask through phase fitting and global optimization and then
      computes a full-field phase map using an arctangent function. Since the phase
      shift evaluation is performed within a local mask, the algorithm is fast compared
      with conventional optimization-based algorithms and typically needs tens of
      seconds to complete the processing. Computer simulation and experimental results
      show that the proposed algorithm has excellent performance compared with state-of
      the-art algorithms. A complete software package of the algorithm in MATLAB is
      available at http://two-shot.sourceforge.io/.

PMID- 29041461
TI  - High-resolution light-scattering imaging with two-dimensional hexagonal
      illumination patterns: system implementation and image reconstruction
      formulations.
AB  - Structured illumination microscopy (SIM) was recently adapted to coherent
      imaging, named structured oblique-illumination microscopy (SOIM), to improve the
      contrast and resolution of a light-scattering image. Herein, we present high
      resolution laterally isotropic SOIM imaging with 2D hexagonal illuminations. The
      SOIM is implemented in a SIM fluorescence system based on a spatial-light
      modulator (SLM). We design an SLM pattern to generate diffraction beams at 0
      degrees  and +/- 60.3 degrees  simultaneously to form a 2D hexagonal
      illumination, and undertake calculations to obtain optimal SLM shifts at 19
      phases to yield a reconstructed image correctly. Beams of linear and circular
      polarizations are used to show the effect of polarization on the resolution
      improvement. We derive the distributions of the electric field of the resultant
      hexagonal patterns and work out the formulations of the corresponding coherent
      scattering imaging for image reconstruction. The reconstructed images of gold
      nanoparticles (100 nm) confirm the two-fold improvement of resolution and reveal
      the effect of polarization on resolving adjacent nanoparticles. To demonstrate
      biological applications, we present the cellular structures of a label-free fixed
      HeLa cell with improved contrast and resolution. This work enables one to perform
      high-resolution dual-mode - fluorescence and light-scattering - imaging in a
      system, and is expected to broaden the applications of SOIM.

PMID- 29041463
TI  - Real-time multi-target ranging based on chaotic polarization laser radars in the
      drive-response VCSELs.
AB  - According to the principle of complete chaos synchronization and the theory of
      Hilbert phase transformation, we propose a novel real-time multi-target ranging
      scheme by using chaotic polarization laser radar in the drive-response vertical
      cavity surface-emitting lasers (VCSELs). In the scheme, to ensure each
      polarization component (PC) of the master VCSEL (MVCSEL) to be synchronized
      steadily with that of the slave VCSEL, the output x-PC and y-PC from the MVCSEL
      in the drive system and those in the response system are modulated by the linear
      electro-optic effect simultaneously. Under this condition, by simulating the
      influences of some key parameters of the system on the synchronization quality
      and the relative errors of the two-target ranging, related operating parameters
      can be optimized. The x-PC and the y-PC, as two chaotic radar sources, are used
      to implement the real-time ranging for two targets. It is found that the measured
      distances of the two targets at arbitrary position exhibit strong real-time
      stability and only slight jitter. Their resolutions are up to millimeters, and
      their relative errors are very small and less than 2.7%.

PMID- 29041464
TI  - Down-conversion RF/photonic link with a monolithically integrated ACP-OPLL phase
      demodulator.
AB  - We present a frequency down conversion RF/photonic link with an attenuation
      counter-propagating optical phase lock loop (ACP-OPLL) photonic integrated
      circuit (PIC) receiver. Frequency down conversion was accomplished by nonlinear
      optical phase modulation in a 2.5mm long transmitter (TX) multi-quantum-well
      (MQW) phase modulator. The down-conversion link demonstrated RF to IF conversion
      loss of ~9dB and spurious free dynamic range (SFDR) of ~118dB?Hz2/3.

PMID- 29041465
TI  - Sensitive and broadband measurement of dispersion in a cavity using a Fourier
      transform spectrometer with kHz resolution.
AB  - Optical cavities provide high sensitivity to dispersion since their resonance
      frequencies depend on the index of refraction. We present a direct, broadband,
      and accurate measurement of the modes of a high finesse cavity using an optical
      frequency comb and a mechanical Fourier transform spectrometer with a kHz-level
      resolution. We characterize 16000 longitudinal cavity modes spanning 16 THz of
      bandwidth in terms of center frequency, linewidth, and amplitude. Using the
      center frequencies we retrieve the group delay dispersion of the cavity mirror
      coatings and pure N2 with 0.1 fs2 precision and 1 fs2 accuracy, as well as the
      refractivity of the 3nu1 + nu3 absorption band of CO2 with 5 * 10-12 precision.
      This opens up for broadband refractive index metrology and calibration-free
      spectroscopy of entire molecular bands.

PMID- 29041466
TI  - Robust optical-frequency-comb based on the hybrid mode-locked Er:fiber
      femtosecond laser.
AB  - We demonstrate an optical frequency comb in which an Er:fiber-based femtosecond
      laser employs nonlinear amplifier loop mirror (NALM) and nonlinear polarization
      evolution (NPE) mode-locking mechanisms. The laser combines advantages of good
      robustness of NALM and low noise feature of NPE. Our experimental results show
      that the hybrid mode-locked laser has high power, low relative intensity noise
      and self-started property, enabling the construction of a robust optical
      frequency comb system. In-loop relative instabilities of both stabilized
      repetition rate and carrier-envelope-offset frequency are well below 1 * 10-17 at
      1 second integration time.

PMID- 29041467
TI  - High-power symmetric-connected uni-traveling-carrier photodiode array integrated
      with sub-wavelength gratings based beam-splitter.
AB  - We present a two-element back-illuminated symmetric-connected uni-traveling
      carrier photodiode array (SC-PDA) integrated with sub-wavelength-gratings based
      beam-splitter (SWGs-BS) for high power optoelectronic applications. The SC-PDA
      with SWGs-BS, a top-illuminated SC-PDA and a single PD were fabricated and
      tested. The proposed SC-PDA with SWGs-BS demonstrates a 3dB bandwidth of
      23.8GHz@60mA, a saturation current of 87.9mA@12GHz and a maximum output RF power
      of ~16dBm@12GHz. Compared to the top-illuminated SC-PDA and the single PD, the
      proposed SC-PDA with SWGs-BS achieved high-power handling capability at low
      coupling complexity and requires no phase-matching techniques in the system.

PMID- 29041468
TI  - Generating laser-pulse enantiomers.
AB  - We present an optical setup capable of mirroring an arbitrary, potentially time
      varying, polarization state of an ultrashort laser pulse. The incident beam is
      split up in two and the polarization of one beam is mirrored by reflection off a
      mirror in normal incidence. Afterwards, both beams are recombined in time and
      space such that two collinear ultrashort laser pulses with mutually mirrored
      polarization, i.e., laser-pulse enantiomers, leave the setup. We employ the Jones
      formalism to describe the function of the setup and analyze the influence of
      alignment errors before describing the experimental implementation and alignment
      protocol. Since no wave plates are utilized, broadband pulses in a large
      wavelength range can be processed. In particular, we show that the setup
      outperforms broadband achromatic wave plates. Furthermore, since the two beams
      travel separately through the optical system they can be blocked independently.
      This opens the possibility for circular dichroism, ellipsometry, and anisotropy
      spectroscopy with shot-to-shot chopping and detection schemes as well as chiral
      coherent control applications.

PMID- 29041469
TI  - Two-dimensional coherent spectroscopy of a THz quantum cascade laser: observation
      of multiple harmonics.
AB  - Two-dimensional spectroscopy is performed on a terahertz (THz) frequency quantum
      cascade laser (QCL) with two broadband THz pulses. Gain switching is used to
      amplify the first THz pulse and the second THz pulse is used to probe the system.
      Fourier transforms are taken with respect to the delay time between the two THz
      pulses and the sampling time of the THz probe pulse. The two-dimensional spectrum
      consists of three peaks at (omegatau = 0, omegat = omega0), (omegatau = omega0,
      omegat = omega0), and (omegatau = 2omega0, omegat = omega0) where omega0 denotes
      the lasing frequency. The peak at omegatau = 0 represents the response of the
      probe to the zero-frequency (rectified) component of the instantaneous intensity
      and can be used to measure the gain recovery.

PMID- 29041470
TI  - Coherence effects in electromagnetically induced transparency in V-type systems
      of 87Rb.
AB  - We present a theoretical and experimental study of electromagnetically induced
      transparency (EIT) in V-type systems of 87Rb atoms. We calculate accurate
      lineshapes of V-type EIT spectra by solving density matrix equations considering
      all the magnetic sublevels involved. The calculated spectra demonstrate
      consistency with the experimental results. We identify the coherence effect in
      the calculated EIT spectra, and determine that the coherence effect exists only
      in the cycling transition. We explain the reason for the suppression of the
      coherence effect in open transitions using an analytical calculation of the
      spectra for a simple V-type three-level atomic system.

PMID- 29041471
TI  - Level-set based mask synthesis with a vector imaging model.
AB  - With continuous shrinking of critical dimension (CD) and the application of
      immersion lithography system to technology nodes 22nm and beyond, the vector
      nature of electromagnetic fields propagating from mask to wafer plane cannot be
      ignored, rendering mask synthesis under scalar imaging model inadequate. In this
      paper, we develop a level-set based optimization framework for mask synthesis
      with a vector imaging model. The forward model of vector image formation is
      established, and then the photomask synthesis is addressed as an inverse imaging
      problem whose variational level-set reformulation is represented by a stable time
      dependent model, which is solved by employing conjugate gradient methods of the
      cost function and readily available finite-difference schemes. Experimental
      results demonstrate pronounced performance in terms of pattern fidelity and edge
      placement error, together with notable computation acceleration and better
      convergence performance.

PMID- 29041472
TI  - Efficient inversion of multiple-scattering model for optical diffraction
      tomography.
AB  - Optical diffraction tomography relies on solving an inverse scattering problem
      governed by the wave equation. Classical reconstruction algorithms are based on
      linear approximations of the forward model (Born or Rytov), which limits their
      applicability to thin samples with low refractive-index contrasts. More recent
      works have shown the benefit of adopting nonlinear models. They account for
      multiple scattering and reflections, improving the quality of reconstruction. To
      reduce the complexity and memory requirements of these methods, we derive an
      explicit formula for the Jacobian matrix of the nonlinear Lippmann-Schwinger
      model which lends itself to an efficient evaluation of the gradient of the data
      fidelity term. This allows us to deploy efficient methods to solve the
      corresponding inverse problem subject to sparsity constraints.

PMID- 29041473
TI  - Uncertainty characterization of particle location from refocused plenoptic
      images.
AB  - Plenoptic imaging is a 3D imaging technique that has been applied for
      quantification of 3D particle locations and sizes. This work experimentally
      evaluates the accuracy and precision of such measurements by investigating a
      static particle field translated to known displacements. Measured 3D displacement
      values are determined from sharpness metrics applied to volumetric
      representations of the particle field created using refocused plenoptic images,
      corrected using a recently developed calibration technique. Comparison of
      measured and known displacements for many thousands of particles allows for
      evaluation of measurement uncertainty. Mean displacement error, as a measure of
      accuracy, is shown to agree with predicted spatial resolution over the entire
      measurement domain, indicating robustness of the calibration methods. On the
      other hand, variation in the error, as a measure of precision, fluctuates as a
      function of particle depth in the optical direction. Error shows the smallest
      variation within the predicted depth of field of the plenoptic camera, with a
      gradual increase outside this range. The quantitative uncertainty values provided
      here can guide future measurement optimization and will serve as useful metrics
      for design of improved processing algorithms.

PMID- 29041474
TI  - Coherent noise reduction in digital holographic microscopy by averaging multiple
      holograms recorded with a multimode laser.
AB  - In digital holographic microscopy (DHM), it is undesirable to observe coherent
      noise in the reconstructed images. The sources of the noise are mainly the
      parasitic interference fringes caused by multiple reflections and the speckle
      pattern caused by the optical scattering on the object surface. Here we propose a
      noise reduction approach in DHM by averaging multiple holograms recorded with a
      multimode laser. Based on the periodicity of the temporal coherence of a
      multimode semiconductor laser, we acquire a series of holograms by changing the
      optical path length difference between the reference beam and object beam.
      Because of the use of low coherence light, we can remove the parasitic
      interference fringes caused by multiple reflections in the holograms. In
      addition, the coherent noise patterns change in this process due to the different
      optical paths. Therefore, the coherent noise can be reduced by averaging the
      multiple reconstructions with uncorrelated noise patterns. Several experiments
      have been carried out to validate the effectiveness of the proposed approach for
      coherent noise reduction in DHM. It is shown a remarkable improvement both in
      amplitude imaging quality and phase measurement accuracy.

PMID- 29041475
TI  - Sub-shot-noise shadow sensing with quantum correlations.
AB  - The quantised nature of the electromagnetic field sets the classical limit to the
      sensitivity of position measurements. However, techniques based on the properties
      of quantum states can be exploited to accurately measure the relative
      displacement of a physical object beyond this classical limit. In this work, we
      use a simple scheme based on the split-detection of quantum correlations to
      measure the position of a shadow at the single-photon light level, with a
      precision that exceeds the shot-noise limit. This result is obtained by analysing
      the correlated signals of bi-photon pairs, created in parametric downconversion
      and detected by an electron multiplying CCD (EMCCD) camera employed as a split
      detector. By comparing the measured statistics of spatially anticorrelated and
      uncorrelated photons we were able to observe a significant noise reduction
      corresponding to an improvement in position sensitivity of up to 17% (0.8dB). Our
      straightforward approach to sub-shot-noise position measurement is compatible
      with conventional shadow-sensing techniques based on the split-detection of light
      fields, and yields an improvement that scales favourably with the detector's
      quantum efficiency.

PMID- 29041476
TI  - Segmented detection SPR sensor based on seven-core fiber.
AB  - By using a seven-core fiber (SCF), we propose and demonstrate a novel segmented
      detection SPR sensor, which solves two bottlenecks about the fiber SPR sensor of
      low sensitivity and the difficulty in the multichannel detection. The proposed
      sensor has ultra high sensitivity and wide detection range because of employing
      the segmented detection technology. Besides that, the proposed sensor employs
      reflection-type time division multiplexing (TDM) technology in fiber multichannel
      detection for the first time. We couple light into and out of the six circularly
      symmetric distributed cores of the seven-core fiber to realize the three channel
      SPR sensing and testing. This three-channel SPR sensor has the advantages of
      detecting biochemical or multi analytes reactions and eliminating the
      distractions due to temperature fluctuations or sample composition variations and
      adsorption of non-target molecules to the sensor surface. This SPR sensor also
      has the advantages of online monitoring by inserting into the blood vessel
      because of its small size. Furthermore, this paper has deeply researched the
      relationship between the refractive index of the solution to be measured, the
      grinding angle of the sensing channel, the sensitivity and the detection range.
      In this paper, we propose a novel segmented detection method which realizes the
      wide detection range with the wider refractive index range of 1.333~1.395 and the
      narrower working bandwidth of 250nm compared with the common SPR sensor, the
      average sensitivity and the maximum sensitivity of the sensor reach 7387.1nm/RIU
      and 8502.5nm/RIU respectively.

PMID- 29041477
TI  - Towards a holographic approach to spherical aberration correction in scanning
      transmission electron microscopy.
AB  - Recent progress in phase modulation using nanofabricated electron holograms has
      demonstrated how the phase of an electron beam can be controlled. In this paper,
      we apply this concept to the correction of spherical aberration in a scanning
      transmission electron microscope and demonstrate an improvement in spatial
      resolution. Such a holographic approach to spherical aberration correction is
      advantageous for its simplicity and cost-effectiveness.

PMID- 29041478
TI  - Advanced active quenching circuit for ultra-fast quantum cryptography.
AB  - Commercial photon-counting modules based on actively quenched solid-state
      avalanche photodiode sensors are used in a wide variety of applications.
      Manufacturers characterize their detectors by specifying a small set of
      parameters, such as detection efficiency, dead time, dark counts rate,
      afterpulsing probability and single-photon arrival-time resolution (jitter).
      However, they usually do not specify the range of conditions over which these
      parameters are constant or present a sufficient description of the
      characterization process. In this work, we perform a few novel tests on two
      commercial detectors and identify an additional set of imperfections that must be
      specified to sufficiently characterize their behavior. These include rate
      dependence of the dead time and jitter, detection delay shift, and "twilighting".
      We find that these additional non-ideal behaviors can lead to unexpected effects
      or strong deterioration of the performance of a system using these devices. We
      explain their origin by an in-depth analysis of the active quenching process. To
      mitigate the effects of these imperfections, a custom-built detection system is
      designed using a novel active quenching circuit. Its performance is compared
      against two commercial detectors in a fast quantum key distribution system with
      hyper-entangled photons and a random number generator.

PMID- 29041479
TI  - Double-channel angular-multiplexing polarization holography with common-path and
      off-axis configuration.
AB  - We propose a double-channel angular-multiplexing polarization holographic imaging
      system with common-path and off-axis configurations. In the system, its input
      plane is spatially divided into three windows: an object window and two reference
      windows, and two orthogonal linear polarizers are attached, respectively, on the
      two reference windows; a two-dimensional cross grating is inserted between the
      input and output planes of the system. Thus the object beam passing through the
      object window and the two orthogonal polarized reference beams passing through
      the two reference windows can overlap each other at the output plane of the
      system and form a double-channel angular-multiplexing polarization hologram (DC
      AM-PH). Using this system, the complex amplitude distributions of two orthogonal
      polarized components from an object can be recorded and reconstructed by one
      single-shot DC-AM-PH at the same time. Theoretical analysis and experimental
      results demonstrated that the system can be used to measure the Jones matrix
      parameters of polarization-sensitive or birefringent materials.

PMID- 29041480
TI  - Computational integral imaging reconstruction of perspective and orthographic
      view images by common patches analysis.
AB  - A novel method to computationally reconstruct perspective and orthographic view
      images with full resolution of a recording device from a single integral
      photograph is proposed. Firstly, a group of image slices that contain full yet
      redundant information to reconstruct the view image are generated, and the object
      surface is divided into pieces by the points that correspond to the centers of
      image slices. Secondly, the image slices that contribute to the pieces are
      extracted and redundant information embedded in them are figured out by common
      patches analysis. Finally, the view image is reconstructed by excluding the
      redundant information and resampling with maximum sampling rate. Each piece of
      the object surface is represented with 9 patches at most from 4 adjacent
      elemental images, and view images with high quality are reconstructed. Both
      simulations and experiments verify the validity of the method.

PMID- 29041481
TI  - Quantum dot white light emitting diodes with high scotopic/photopic ratios.
AB  - Alloy core/shell CdxZn1-xS/ZnS quantum dots (QDs) are emerging as robust
      candidates for light-emitting diodes (LEDs), however the emission range of the
      current CdxZn1-xS/ZnS is quite limited, ranging from 390 to 470 nm. It still
      remains a challenging task to construct white LEDs based on current CdxZn1-xS/ZnS
      system. Here, a versatile ZnSe with a moderate band gap is introduced onto the
      Cd0.1Zn0.9S core. The ZnSe shell, on one hand, can passivate the core surface
      which leads to bright emissions. On the other hand, it is essential in extending
      the emission to red region so that the emission wavelengths of Cd0.1Zn0.9S/ZnS
      and Cd0.1Zn0.9S/ZnSe QDs can cover the whole visible region, which is very
      important for white LED applications. Two- and four-hump QD-based LEDs are
      computationally and experimentally investigated. Results show that four-hump
      quantum dot light-emitting diodes (QLED) have better performances than the two
      hump one, in the luminous and the vision properties. The fabricated white LEDs
      (WLEDs) based on Cd0.1Zn0.9S/ZnS and Cd0.1Zn0.9S/ZnSe QDs exhibits a
      scotopic/photopic ratio (S/P) ratio as high as 2.52, which exceeds the current
      limit of 2.50 by common lighting technologies, a color rendering index of 90.3, a
      luminous efficacy of optical radiation of 460.78 lumen per unit optical power,
      and a correlated color temperature of 5454 K. These results suggest that CdxZn1
      xS/ZnS and CdxZn1-xS/ZnSe quantum dots serving as emitters hold great promise for
      the next-generation white light source with better S/P ratio.

PMID- 29041482
TI  - Time-domain multiplexed high resolution fiber optics strain sensor system based
      on temporal response of fiber Fabry-Perot interferometers.
AB  - We developed a multiplexed strain sensor system with high resolution using fiber
      Fabry-Perot interferometers (FFPI) as sensing elements. The temporal responses of
      the FFPIs excited by rectangular laser pulses are used to obtain the strain
      applied on each FFPI. The FFPIs are connected by cascaded couplers and delay
      fiber rolls for the time-domain multiplexing. A compact optoelectronic system
      performing closed-loop cyclic interrogation is employed to improve the sensing
      resolution and the frequency response. In the demonstration experiment, 3-channel
      strain sensing with resolutions better than 0.1 nepsilon and frequency response
      higher than 100 Hz is realized.

PMID- 29041483
TI  - Nanopatterned luminescent concentrators for visible light communications.
AB  - Visible light communication (VLC) is a promising candidate for high-speed
      wireless communication with numerous unlicensed spectrum. To achieve high-speed
      data communication, it requires intense light signals concentrated on a tiny fast
      photodiode. The common way of using focusing optics reduces the field of view
      (FoV) of the photodiode due to the conservation of etendue. Luminescent solar
      concentrators (LSC) provide a solution to enhance the signals without affecting
      the FoV. In this paper we demonstrate nanopatterned LSCs fabricated on flexible
      plastics that achieve a doubling of optical gain compared to its traditional
      rectangular counterparts. These LSCs can free VLC detectors from complex active
      pointing and tracking systems, making them compatible with smart mobile terminals
      in a simple fashion.

PMID- 29041484
TI  - Large mode area inverse index fiber with a graded index profile for high power
      single mode operation.
AB  - We propose a new gain fiber structure with an inverse index profile for high
      power amplification of a Gaussian single mode beam. A large mode area (LMA)
      design can be fulfilled with the inverse index profile by implementing a graded
      index in the depressed core. We numerically show that the proposed gain fiber can
      guide a single mode Gaussian beam with a large beam area and amplify the beam to
      a kW level output power.

PMID- 29041485
TI  - Scan-less hyperspectral dual-comb single-pixel-imaging in both amplitude and
      phase.
AB  - We have developed a hyperspectral imaging scheme that involves a combination of
      dual-comb spectroscopy and Hadamard-transform-based single-pixel imaging. The
      scheme enables us to obtain 12,000 hyperspectral images of amplitude and phase at
      a spatial resolution of 46 um without mechanical scanning. The spectral
      resolution given by the data point interval in the frequency domain is 20 MHz and
      the comb mode interval is 100 MHz over a spectral range of 1.2 THz centered at
      191.5 THz. As an initial demonstration of our scheme, we obtained spectroscopic
      images of a standard test chart through an etalon plate. The thickness of an
      absorptive chromium-coated layer on a float-glass substrate was determined to be
      70 nm from the hyperspectral phase images in the near-infrared wavelength region.

PMID- 29041487
TI  - 3D image distortion problem in digital in-line holographic microscopy and its
      effective solution.
AB  - Digital in-line holographic microscopy (DIHM) has attracted attention because of
      its simple but powerful three-dimensional (3D) imaging capability. To improve the
      spatial resolution, 3D image reconstruction algorithms use numerical
      magnification, which generates distortions in the generated images. We propose a
      method to overcome this problem by using the simple relation between the object
      and image positions in 3D space. Several holograms were taken while translating a
      resolution target at different axial positions by a motorized stage. We
      demonstrated the effectiveness of our method by reconstructing the 3D positions
      of 3-MUm-diameter polymer beads on a tilted slide glass from a single measured
      hologram.

PMID- 29041486
TI  - Edge smoothness enhancement in DMD scanning lithography system based on a
      wobulation technique.
AB  - The resolution of digital micro-mirror device (DMD) scanning lithography is
      limited in the transverse direction (the scanning direction is vertical) as a
      result of the compacted size of the DMD micro-mirror and the low magnification of
      the projection lens. Above-stated restrictions lead to an unsatisfactory saw
      tooth edge (size ~one DMD pixel) after the lithography process within all
      directions except for the scanning orientation. In order to smooth the edge, an
      optimized sub-pattern construction method, described as the combination of
      wobulation techniques and the continuous scanning lithography process, is
      proposed. Afterward, lithography experiments were implemented by introducing the
      wobulation techniques within the DMD scanning lithography system. The
      experimental results show that the saw-tooth edge is reduced to nearly 0.5 pixel
      size after 1/2 pixel dislocation superposition exposure, and is even scaled down
      to less than 0.1 pixel after 1/4 pixel dislocation superposition exposure. At
      this point, the edge of the lithography pattern is appropriately smoothed. The
      effectiveness of the above-mentioned method that improves the edge smoothness of
      the lithography pattern is demonstrated.

PMID- 29041488
TI  - 12 J, 10 Hz diode-pumped Nd:YAG distributed active mirror amplifier chain with
      ASE suppression.
AB  - Experimental amplification of 10-ns pulses to an energy of 12.2 J at the
      repetition rate of 1-10 Hz is reported from a diode-pumped room-temperature
      distributed active mirror amplifier chain (DAMAC) based on Nd:YAG slabs.
      Efficient power scaling at the optical-optical efficiency of 20.6% was achieved
      by suppressing the transverse parasitic oscillation with ASE absorbers. To the
      best of our knowledge, this is the first demonstration of a diode-pumped Nd:YAG
      active-mirror laser with nanosecond pulse energy beyond 10 joules. The verified
      DAMAC concept holds the promise of scaling the energy to a 50 J level and higher
      by adding 10-12 more pieces of active mirror in the chain.

PMID- 29041489
TI  - Novel dual-loop optoelectronic oscillator based on self-polarization
      stabilization technique.
AB  - A novel dual-loop optoelectronic oscillator (OEO) based on self-polarization
      stabilization technique has been experimentally demonstrated. The input light in
      each loop will retrace its path through a 45 degrees  Faraday rotator and single
      mode fiber with different length after reflecting off a 45 degrees  Faraday
      rotator mirror. By this way, the polarization state of the output signal is
      always rotated by 180 degrees  from the polarization state of the input signal in
      each loop even if the round-trip fiber is perturbed by the mechanical vibration
      or temperature. Moreover, the required fiber length is cut in half due to the
      round-trip transmission in each path, resulting in higher system stability and
      more compacter structure. The experimental results show that in an intensity
      modulator (IM)-based OEO system, this scheme has better phase noise performance
      than the traditional polarization multiplexing method. Furthermore, to avoid the
      DC bias drifting problem of IM, a simple phase modulation to intensity modulation
      convertor by using a polarization-dependent phase modulator and a polarizer is
      proposed without the need of expensive optical filters or dispersive devices.
      Based on this scheme, a novel dual-loop OEO using phase modulator and self
      polarization-stabilization technique has been experimentally demonstrated. The
      phase noise of -114.1 dBc/Hz at 10 kHz away from the carrier (10 GHz) is achieved
      and the side mode suppression ratio is improved to 63 dB.

PMID- 29041490
TI  - Experimental demonstration of a 24-port packaged multi-microring network-on-chip
      in silicon photonic platform.
AB  - A 24-port packaged multi-microring optical network-on-chip has been tested for
      simultaneous co- and counter-propagating transmissions at the same wavelength at
      10 Gbps. In the co-propagating scenario communications up to five hops with one
      interfering signal have been tested, together with transmissions impaired by up
      to three interfering signals. In the counter-propagating scenario the device
      performance has been investigated exploiting the ring resonators in both shared
      source and shared-destination configurations. The spectral characterization is in
      good agreement with the theoretical results. Bit-error-rate measurements indicate
      power penalties at BER=10-9 limited to (i) 0.5 dB in the co-propagating scenarios
      independently from the number of interfering transmissions, (ii) 0.8 dB in the
      counter-propagating scenario with shared-source configuration, and (iii) 2 dB in
      the counter-propagating scenario with shared-destination configuration.

PMID- 29041491
TI  - Abnormal chiral events in a semiconductor laser with coherent injection.
AB  - We study experimentally and theoretically the dynamics of a spatially extended
      (along the propagation direction) oscillatory medium with coherent forcing. We
      observe abnormally high events, responsible for a different statistics of
      intensity and pulse height, in a regime where solitons and roll patterns are
      unstable. We focus on the formation of these high-peak events and their
      connection to the phase dynamics. Each abnormal event can be associated with a
      change in the slope of the phase time trace. Furthermore, the coexistence of +/
      2pi phase rotations inside the cavity can be associated to the observation of
      abnormal events, similarly to recent predictions in bidimensional vortex
      turbulence.

PMID- 29041492
TI  - Compact high-efficiency perfectly-vertical grating coupler on silicon at O-band.
AB  - A compact, high-efficiency grating coupler is demonstrated for interfacing a
      silicon waveguide and a perfectly-vertical fiber at O-band. The grating lies on a
      tilted silicon membrane for minimizing the reflections. Circular grating lines
      are adopted to shorten the overall device length to about 60MUm. 57% peak
      coupling efficiency and >28nm 1-dB coupling bandwidth are obtained
      experimentally. Back reflections of 1% to the silicon waveguide and the single
      mode fiber are theoretically estimated. The processing flow to realize the
      proposed structure is discussed in detail. The fabrication control over the
      tilted angle of the silicon membrane is investigated. The approach by applying an
      oxide cladding to improve the stability of the membrane is also introduced. The
      present grating coupler is compatible to common fabrication processes for silicon
      photonic chips.

PMID- 29041493
TI  - Flexible, all-dielectric metasurface fabricated via nanosphere lithography and
      its applications in sensing.
AB  - In this letter, we report a flexible, all-dielectric metasurface fabricated via
      nanosphere lithography (NSL) and demonstrate its potentials in sensing
      applications. Regularly arrayed Si cylinders with hexagonal lattice fabricated on
      polyethylene terephthalate (PET) flexible substrate are exploited to detect
      applied strain and surface dielectric environment by measuring transmission
      spectra. Further numerical simulations coincide with experimental observations.
      The transmission peak can be attributed to coupled magnetic Mie resonance between
      close-packed Si cylinders. Such Mie resonance based sensor with high flexibility
      offers an alternative approach towards detecting surrounding variations besides
      traditional plasmon resonance based sensors, and provides more choices for
      designing photonic devices operating in the optical regime.

PMID- 29041494
TI  - Secure multiple access for indoor optical wireless communications with time-slot
      coding and chaotic phase.
AB  - In this paper, we report a novel mechanism to simultaneously provide secure
      connections for multiple users in indoor optical wireless communication systems
      by employing the time-slot coding scheme together with chaotic phase sequence.
      The chaotic phase sequence is generated according to the logistic map and applied
      to each symbol to secure the transmission. Proof-of-concept experiments are
      carried out for multiple system capacities based on both 4-QAM and 16-QAM
      modulation formats, i.e. 1.25 Gb/s, 2 Gb/s and 2.5 Gb/s for 4-QAM, and 2.5 Gb/s,
      3.33 Gb/s and 4 Gb/s for 16-QAM. Experimental results show that in all cases the
      added chaotic phase does not degrade the legitimate user's signal quality while
      the illegal user cannot detect the signal without the key.

PMID- 29041495
TI  - Dual-band dechirping LFMCW radar receiver with high image rejection using
      microwave photonic I/Q mixer.
AB  - In this paper, a photonics-based dual-band linear frequency-modulated continuous
      wave (LFMCW) radar receiver is proposed. The system core is a microwave photonic
      in-phase and quadrature (I/Q) mixer, whose inherent large bandwidth, high I/Q
      balance and favorable uniformity enable the receiver to operate over an extremely
      wide frequency range. An integrated dual-band waveform offers the possibility of
      independent detection, allowing the sharing of hardware resources and joint
      dechirp processing of dual bands. In the proof-of-concept experiment, the
      distance measurements of S- and C-bands are implemented, with a high and uniform
      image rejection exceeding 28 and 30 dB, respectively. The image rejections of the
      two bands can be further improved to 43 and 41 dB at least by digital signal
      processing (DSP). The proposed photonic-assisted receiver is thus able to
      simplify the architecture and improve performance for the multispectral sensing
      application.

PMID- 29041496
TI  - Demonstration of an all-optical feed-forward delay line buffer using the
      quadratic Stark effect and two-photon absorption in an SOA.
AB  - We have inserted into an unbiased semiconductor optical amplifier (SOA) a
      powerful control beam, with photon energy slightly smaller than that of the band
      gap of its active region, for exciting two-photon absorption and the quadratic
      Stark effect. For the available SOA, we estimated these phenomena generated a
      nonlinear absorption coefficient beta= -865 cm/GW and induced an appreciable
      birefringence inside the amplifier waveguide, which significantly modified the
      polarization-state of a probe beam. Based on these effects, we have
      experimentally demonstrated the operation of an all-optical buffer, using an 80
      Gb/s optical pulse comb, as well as an unbiased SOA, which was therefore, devoid
      of amplified spontaneous emission and pattern effects.

PMID- 29041497
TI  - Anisotropic light propagation in bovine muscle tissue depends on the initial
      fiber orientation, muscle type and wavelength.
AB  - The effects of fiber orientation on vis/NIR light propagation were studied in
      three bovine muscles: biceps brachii, brachialis and soleus. Broadband light was
      focused onto the sample and the diffuse reflectance spot was captured using a
      hyperspectral camera (470-1620 nm), after which rhombuses were fitted to equi
      intensity points. In samples with fibers running parallel to the measurement
      surface, the rhombus' major axis was oriented perpendicular to the fiber
      direction close to the point of illumination. However, at larger distances from
      the illumination spot, the major axis orientation aligned with the fiber
      direction. This phenomenon was found to be muscle dependent. Furthermore, the
      rhombus orientation was highly dependent on the sample positioning underneath the
      camera, especially when the muscle fibers ran parallel to the measurement
      surface. The bias parameter, indicating the deviation from a circular shape, was
      higher for samples with the fibers running parallel to the measurement surface.
      Moreover, clear effects of wavelength and distance from the illumination point on
      this parameter were observed. These results show the importance of fiber
      orientation when considering optical techniques for measurements on anisotropic,
      fibrous tissues. Moreover, the prediction of muscle fiber orientation seemed
      feasible, which can be of interest to the meat industry.

PMID- 29041498
TI  - Manipulating electromagnetic wave propagating non-reciprocally by a chain of
      ferrite rods.
AB  - We demonstrated that non-reciprocal wave propagation could be manipulated by a
      magnetic rod chain under bias DC magnetic fields. Made of ferrite material YIG
      and designed working in the microwave X-band, the rod chain exhibited almost a
      total reflection when the incident wave obliquely impinged on the rod chain, but
      exhibited nearly a total transmission when the wave reversed its propagation
      direction. The non-reciprocal wave propagation was due to the non-reciprocal
      diffraction of the rod chain for the orders 0 and +/- 1. Further, the non
      reciprocal wave propagation was directly observed by using the field mapping
      technique. The unique non-reciprocal wave property of the magnetic rod chain
      provides a new way to control the flow of EM waves.

PMID- 29041499
TI  - Interactions between self-accelerating beams in photorefractive media.
AB  - We investigate interactions between in-phase or out-of-phase Airy beams and
      nonlinear accelerating beams in photorefractive crystals by means of direct
      numerical simulations. Since self-accelerating beams possess infinite energy, we
      evaluated the propagation of two shifted counter beams by truncating the
      oscillating tails. The numerical results show that the external bias electric
      field has a profound effect on the propagation dynamics and the solitons shed
      from the Airy beam. We also found that during interactions between two nonlinear
      accelerating beams, single solitons, soliton pairs, and bound breathing solitons
      were produced. When the nonlinear accelerating beam collides with a soliton beam,
      the main lobe continues accelerating while the soliton intensity fluctuates with
      the lobes.

PMID- 29041500
TI  - 1.5MUm, mode-hop-free full C-band wavelength tunable laser diode with a linewidth
      of 8 kHz and a RIN of -130 dB/Hz and its extension to the L-band.
AB  - We demonstrate a narrow-linewidth, low-intensity noise, widely wavelength-tunable
      LD for which we adopted a long external cavity configuration (ECLD) with a
      tunable optical filter. By employing a simultaneous tuning circuit between the
      optical filter and the Fabry-Perot mode caused by the external cavity, the
      oscillation wavelength was successfully tuned over the full C-band without mode
      hopping. The tunable optical filter bandwidth was 0.55 nm (1530~1570 nm). We
      achieved a linewidth of less than 8 kHz obtained with a delayed self-heterodyne
      method. On the other hand, the linewidth estimated from the white noise level of
      the optical frequency modulation noise power spectrum of the laser output was as
      narrow as 314 Hz. A relative intensity noise (RIN) below -130 dB/Hz was
      simultaneously achieved over the C-band range. With the same configuration except
      for an optical filter with a filter bandwidth of 0.6 nm for L-band operation
      (1570~1610 nm), we also realized a full L-band wavelength tunable ECLD with a
      linewidth of less than 7.7 kHz and a RIN of below -126 dB/Hz.

PMID- 29041501
TI  - Measurement of spectacle lenses using wavefront aberration in real view
      condition.
AB  - A wavefront aberration analysis method for measuring spectacle lenses in real
      view condition is proposed and verified using experimental apparatus based on the
      eye-rotation model. Two strategies-feedback positioning and posture adjustment of
      incident beams and Hartmann-Shack wavefront-aberration sensor calibration at each
      measurement subarea-are applied to improve measurement accuracy. By simulating
      the real-view condition, wavefront aberration and user power on the vertex sphere
      can be obtained. Comparison experiments demonstrate the validity and accuracy of
      the proposed method and experimental apparatus. Freeform progressive addition
      lenses are also measured and the results analyzed. The findings provide a
      possible approach for optimizing the design of spectacle lenses and evaluating
      their manufacturing and imaging quality.

PMID- 29041502
TI  - Plasmon-enhanced LT-GaAs/AlAs heterostructure photoconductive antennas for sub
      bandgap terahertz generation.
AB  - Photocurrent generation in low-temperature-grown GaAs (LT-GaAs) has been
      significantly improved by growing a thin AlAs isolation layer between the LT-GaAs
      layer and semi-insulating (SI)-GaAs substrate. The AlAs layer allows greater
      arsenic incorporation into the LT-GaAs layer, prevents current diffusion into the
      GaAs substrate, and provides optical back-reflection that enhances below bandgap
      terahertz generation. Our plasmon-enhanced LT-GaAs/AlAs photoconductive antennas
      provide 4.5 THz bandwidth and 75 dB signal-to-noise ratio (SNR) under 50 mW of
      1570 nm excitation, whereas the structure without the AlAs layer gives 3 THz
      bandwidth, 65 dB SNR for the same conditions.

PMID- 29041503
TI  - Dual-band and polarization-independent infrared absorber based on two-dimensional
      black phosphorus metamaterials.
AB  - Two-dimensional (2D) black phosphorus (BP) with direct band gap, bridges the
      characteristics of graphene with a zero or near-zero band gap and transition
      metal dichalcogenides with a wide band gap. In the infrared (IR) regime, 2D BP
      materials can attenuate electromagnetic energy due to losses derived from its
      surface conductivity. This paper proposes an IR absorber based on 2D BP
      metamaterials. It consists of multi-layer BP-based nano-ribbon pairs, each formed
      by two orthogonally stacked nano-ribbons. The multi-layer BP metamaterials and
      bottom gold mirror together form a Fabry-Perot resonator that could completely
      inhibit light transmission to create strong absorption through the BP
      metamaterials. Unlike previously reported BP metamaterial absorbers, this new
      structure can operate at two frequency bands with absorption > 90% in each owning
      to the first-order and second-order Fabry-Perot resonant frequencies. It is also
      polarization independent due to the fourfold rotational structural symmetry. To
      our best knowledge, this is the first report on using BP metamaterials in an
      absorber that operates independent of polarization and in dual bands.

PMID- 29041504
TI  - Tunable silicon-based all-dielectric metamaterials with strontium titanate thin
      film in terahertz range.
AB  - Silicon-based all-dielectric metamaterials (SAMs), with advantages like low loss
      and simple structure, are attracting more and more attention. However, SAMs
      usually suffer from narrow bandwidth and low tunability, and thereby their
      applications are seriously impeded. In this work, we propose and experimentally
      demonstrate a tunable SAMs in terahertz (THz) ranges by covering the SAMs with a
      layer of active medium, strontium titanate (STO). It shows that the THz responses
      of SAMs can be thermally tuned due to the temperature-dependent permittivity of
      STO. This work provides a convenient route to tunable SAMs from THz to optical
      ranges.

PMID- 29041505
TI  - Dual-beam manually-actuated distortion-corrected imaging (DMDI) with micromotor
      catheters.
AB  - We present a new paradigm for performing two-dimensional scanning called dual
      beam manually-actuated distortion-corrected imaging (DMDI). DMDI operates by
      imaging the same object with two spatially-separated beams that are being
      mechanically scanned rapidly in one dimension with slower manual actuation along
      a second dimension. Registration of common features between the two imaging
      channels allows remapping of the images to correct for distortions due to manual
      actuation. We demonstrate DMDI using a 4.7 mm OD rotationally scanning dual-beam
      micromotor catheter (DBMC). The DBMC requires a simple, one-time calibration of
      the beam paths by imaging a patterned phantom. DMDI allows for distortion
      correction of non-uniform axial speed and rotational motion of the DBMC. We show
      the utility of this technique by demonstrating en face OCT image distortion
      correction of a manually-scanned checkerboard phantom and fingerprint scan.

PMID- 29041506
TI  - Divide and update: towards single-shot object and probe retrieval for near-field
      holography.
AB  - We present a phase reconstruction scheme for X-ray near-field holographic imaging
      based on a separability constraint for probe and object. In order to achieve
      this, we have devised an algorithm which requires only two measurements - with
      and without an object in the beam. This scheme is advantageous if the standard
      flat-field correction fails and a full ptychographic dataset can not be acquired,
      since either object or probe are dynamic. The scheme is validated by numerical
      simulations and by a proof-of-concept experiment using highly focused undulator
      radiation of the beamline ID16a of the European Synchrotron Radiation Facility
      (ESRF).

PMID- 29041507
TI  - Polarization- and wavelength-independent SBS-based filters for high resolution
      optical spectrum measurement.
AB  - A polarization-independent narrow passband optical filter with a FWHM bandwidth
      of ~10 MHz based on stimulated Brillouin scattering (SBS) effect is proposed and
      experimentally demonstrated. By optimizing the parameters of a depolarizer
      consisting of a power-splitting Mach-Zehnder interferometer (MZI) structure,
      degree of polarization (DOP) of the pump source can be reduced to less than 5%.
      Consequently frequency response of the SBS-based filter remains almost unchanged
      when the state of polarization (SOP) of the input signal varies and the
      corresponding polarization-dependent gain (PDG) is less than 1 dB. And the
      experimental results also indicate that the proposed filter can realize the
      wavelength-independent operation over a range of ~30 nm. Furthermore, high
      resolution optical spectrum measurement utilizing this novel filter is
      investigated. For an input signal with a frequency interval of 30 MHz in
      arbitrary SOP, spectral details can be clearly observed and the power stability
      of the measured spectra can be improved from 3~5 dB to less than 0.5 dB, which
      benefitting from the polarization independent operation of the forementioned
      filter. Moreover, considering the resolution degradation of the measured spectra
      induced by the frequency shift in the depolarizer, a sweep speed of 5 nm/s for
      the pump source and a delayed fiber length of 2000 m in the MZI should be used to
      guarantee the desired high spectral resolution of ~10 MHz.

PMID- 29041508
TI  - Mask aligner lithography using laser illumination for versatile pattern
      generation.
AB  - Mask aligner lithography is a well-established back-end fabrication process in
      microlithography. Within the last few years, resolution enhancement techniques
      have been transferred and adapted from projection lithography to further develop
      mask aligner lithography, especially concerning achievable resolution.
      Nonetheless, current technology using a mercury vapor lamp as a light source has
      reached its limits, e.g. for high-resolution pattering. Within this paper, we
      present the extension of the existing mask aligner illumination system by
      replacing the mercury vapor lamp with a solid-state laser. Full-field mask
      aligner lithography is guaranteed by a rotating diffuser expanding the laser beam
      and minimizing undesired speckle effects. An additional integrated galvanometer
      scanner allows a flexible choice of arbitrary angular spectrum distributions of
      the photomask illumination. We show versatile results like simple binary patterns
      of squares and triangles, as well as a more complex lateral shape like a blazed
      grating.

PMID- 29041509
TI  - Measurement system and model for simultaneously measuring 6DOF geometric errors.
AB  - A measurement system to simultaneously measure six degree-of-freedom (6DOF)
      geometric errors is proposed. The measurement method is based on a combination of
      mono-frequency laser interferometry and laser fiber collimation. A simpler and
      more integrated optical configuration is designed. To compensate for the
      measurement errors introduced by error crosstalk, element fabrication error,
      laser beam drift, and nonparallelism of two measurement beam, a unified
      measurement model, which can improve the measurement accuracy, is deduced and
      established using the ray-tracing method. A numerical simulation using the
      optical design software Zemax is conducted, and the results verify the
      correctness of the model. Several experiments are performed to demonstrate the
      feasibility and effectiveness of the proposed system and measurement model.

PMID- 29041510
TI  - Three-dimensional flame measurements with large field angle.
AB  - A system for three-dimensional computed tomography of chemiluminescence was
      developed to measure flames over a large field angle. Nine gradient-index rods,
      with a 9 * 1 endoscope and only one camera are used. Its large field of view,
      simplicity, and low cost make it attractive for inner flow field diagnostics. To
      study the bokeh effect caused by the imaging system on reconstruction solutions,
      fluorescent beads were used to determine the blurring function. Experiments using
      a steady diffusion flame were conducted to validate the system. Three models,
      namely the clear-imaging, out-of-focus imaging, and deconvolution models, were
      utilized. Taking the bokeh effect into account, the results suggest that based on
      run-times the deconvolution model provides the best reconstruction accuracy
      without increasing computational time.

PMID- 29041511
TI  - Stable and wavelength- selectable C + L band fiber ring laser with single
      longitudinal-mode by utilizing C-band erbium fiber amplifier.
AB  - In the investigation, we propose and demonstrate a wavelength-selectable C- plus
      L-band erbium-doped fiber (EDF) ring laser with single-longitudinal-mode (SLM)
      output. Here, a C-band erbium-doped fiber amplifier (EDFA) is utilized to serve
      as gain medium together with proposed multi-cross-ring (MCR) scheme to extend the
      wavelength tunability to L-band range. Besides, the MCR can also suppress the
      multi-longitudinal-mode (MLM) significantly. Therefore, the measured output power
      and optical signal to noise ratio (OSNR) of each lasing wavelength are between 
      10.1 and -2.7 dBm, and 26.4 and 35.0 dB/0.06 nm, respectively in the wavelength
      range from 1530.0 to 1584.0 nm. In addition, the output stabilities of power and
      wavelength in the proposed EDF MCR laser have been also analyzed experimentally.

PMID- 29041512
TI  - Self-selection mechanism of Fabry-Perot micro/nanoscale wire cavity for single
      mode lasing.
AB  - Developing micro/nanoscale wire (MNW) lasers with single-mode operation is
      critical for realizing their practical applications, however, most reported MNW
      lasers operate in multi-modes, because lacking of mode selection mechanisms. In
      this work, a simple and direct way to realize stable, single-mode MNW laser
      without complicated micro/nano-manipulation was demonstrated. We have found and
      proved that the position of the active region plays a key role in determining the
      lasing mode of MNW lasers, which can be used to realize single-mode lasing in
      MNWs. We propose self-selection mechanism of Fabry-Perot MNW cavity for single
      mode lasing due to location-dependent field distribution in MNWs, which is
      characterized by suppressing the multiple longitudinal mode oscillation of the
      MNW laser. GaN MNW lasers with different lengths and diameters have been
      fabricated, verifying the self-selection mechanism of the cavity experimentally.
      Moreover, we demonstrate the single-mode, room temperature optically pumped MNW
      laser with an extremely low threshold (~40 kW/cm2) in condition of appropriate
      cavity length, opening an opportunity to realize stable single-mode, low
      threshold MNW laser for easy integration in constructing micro/nanoscale photonic
      and optoelectronic circuits and devices.

PMID- 29041513
TI  - 946 nm Nd: YAG double Q-switched laser based on monolayer WSe2 saturable
      absorber.
AB  - In this paper, we report a 946nm double Q-switched laser side pumped by an 808-nm
      pulse laser diode (LD). A layered tungsten diselenide (WSe2) saturable absorber
      (SA) together with an MgO doped LiNbO3 electro-optic (EO) modulator is applied to
      double Q-switch the Nd: YAG laser, producing trains of nanosecond-duration pulses
      with 500 Hz repetition rate. Such WSe2 saturable absorbers are fabricated by
      chemical vapor deposition (CVD) in a hot wall chamber and then embedded into a
      resonant mirror. The achieved pulse energy of double Q-switched laser at 946 nm
      is approximately 2.63 mJ with 10.8 ns pulse width and the peak power is round 244
      kW, corresponding to the beam quality factors of M2x = 3.846,M2y = 3.861.
      Monolayer WSe2 nanosheets applied in the experiment would be a promising SA for
      passive Q-switching operation.

PMID- 29041514
TI  - Nonlinear polarization instability in cubic-quintic plasmonic nanocomposites.
AB  - We report a study of the nonlinear birefringence induced in a metal-dielectric
      nanocomposite due to the contributions of third- and fifth-order optical
      nonlinearities. A theoretical model describing the evolution of the light
      polarization state of a confined laser beam propagating through the nonlinear
      medium is developed with basis on a pair of coupled dissipative cubic-quintic
      nonlinear differential equations related to the two orthogonal polarizations of
      the optical field. As a proof-of-principle experiment we demonstrate the control
      of the light beam polarization in a silver-nanocolloid by changing the silver
      nanoparticles volume fraction, f, and the light intensity. A large nonlinear
      phase-shift (~20pi) was observed using a 9 cm long capillary filled with silver
      nanoparticles suspended in carbon disulfide. Experiments using colloids with
      1.0*10-5<=f<=4.5*10-5 and maximum light intensities of tens of MW/cm2 are
      performed. In addition, we demonstrate that the modulation instability is highly
      sensitive to the quintic nonlinearity contribution performed showing good
      agreement with the experimental results.

PMID- 29041515
TI  - Quasi-phase-matching of high-order harmonics in plasma plumes: theory and
      experiment.
AB  - We theoretically analyze the phase-matching of high-order harmonic generation
      (HHG) in multi-jet plasmas and find the harmonic orders for which the quasi-phase
      matching (QPM) is achieved depending on the parameters of the plasma and the
      generating beam. HHG by single- and two-color generating fields is analyzed. The
      QMP is studied experimentally for silver, indium and manganese plasmas using near
      IR and mid-IR laser fields. The theory is validated by comparison with our
      experimental observations, as well as published experimental data. In particular,
      the plasma densities and the harmonic phase coefficients reconstructed from the
      observed harmonic spectra using our theory agree with the corresponding
      parameters found using other methods. Our theory allows defining the plasma jet
      and the generating field properties, which can maximize the HHG efficiency due to
      QPM.

PMID- 29041516
TI  - Shortcut to adiabatic passage in a three-level system via a chosen path and its
      application in a complicated system.
AB  - We construct a shortcut to an adiabatic passage in a three-level system by
      choosing a dressed state acting as an evolutive path. Two designed auxiliary
      pulses are added into the original pulses to eliminate the couplings between the
      chosen evolutive-path state and the other two dressed states. The same target
      state as one gotten by adiabatic passage can be rapidly obtained, and the
      population of the lossy intermediate state can be controlled by setting proper
      parameters. Furthermore, as an example, we use this method in the adiabatic
      passage scheme [Opt. Express20, 014547 (2012)], a complicated cavity quantum
      electrodynamics system, to successfully accelerate the generation of the three
      dimensional entanglement between a single atom and a Bose-Einstein condensate.

PMID- 29041517
TI  - Phase demodulation of interferometric fiber sensor based on fast Fourier
      analysis.
AB  - A demodulation method for interferometric fiber sensors (IFSs) is proposed in
      this article. The phase variation induced by the measurands can be estimated by
      calculating the Fourier phase at the intrinsic spatial frequencies of the fiber
      sensor. Theoretical analysis of the demodulation method is discussed in detail.
      Numerical simulations are put forward to demonstrate the consistency of the
      demodulation results under different wavelength sampling interval and noise
      level, showing a better stability compared with the conventional peak wavelength
      tracking technique. The proposed method is also experimentally demonstrated by an
      inline multimode interferometer based on a single-mode fiber (SMF) offset
      splicing structure. Experimental results indicate that the phase response of
      different cladding modes can be analyzed simultaneously. Simultaneous measurement
      of strain and temperature is realized in our confirmatory experiment by analyzing
      the phase sensitivities of two selected cladding modes.

PMID- 29041518
TI  - Precision improvement of surface plasmon resonance sensors based on weak-value
      amplification.
AB  - In this paper, a method to improve the precision of prism-coupler-based surface
      plasmon resonance (SPR) sensors using weak-value amplification (WVA) is
      presented. A general theory model to describe the post-selected SPR sensing
      system is established and the polarization-dependent amplitude and phase
      evolutions induced by the SPR are regarded as the weak interactions in the WVA
      formalism. As a consequence of WVA, the detected signal can be enhanced with
      respect to the technical noise which is dependent on the post-selected light
      intensity. The precision of our method reaches 2.9 * 10-7RIU, which is improved
      nearly one order of magnitude compared to the conventional sensing technique.

PMID- 29041519
TI  - Broadband two-dimensional electronic spectroscopy in an actively phase stabilized
      pump-probe configuration.
AB  - We introduce a novel configuration for two-dimensional electronic spectroscopy
      (2DES) that combines the partially collinear pump-probe geometry with active
      phase locking. We demonstrate the method on a solution sample of CdSe/ZnS
      nanocrystals by employing two non-collinear optical parametric amplifiers as the
      pump and probe sources. The two collinear pump pulse replicas are created using a
      Mach-Zehnder interferometer phase stabilized by active feedback electronics.
      Taking the advantage of separated paths of the two pump pulses in the
      interferometer, we improve the signal-to-noise ratio with double modulation of
      the individual pump beams. In addition, a quartz wedge pair manipulates the phase
      difference between the two pump pulses, enabling the recovery of the rephasing
      and non-rephasing signals. Our setup integrates many advantages of available 2DES
      techniques with robust phase stabilization, ultrafast time resolution, two-color
      operation, long delay scan, individual polarization manipulation and the ease of
      implementation.

PMID- 29041520
TI  - Large area optical mapping of surface contact angle.
AB  - Top-down contact angle measurements have been validated and confirmed to be as
      good if not more reliable than side-based measurements. A range of samples,
      including industrially relevant materials for roofing and printing, has been
      compared. Using the top-down approach, mapping in both 1-D and 2-D has been
      demonstrated. The method was applied to study the change in contact angle as a
      function of change in silver (Ag) nanoparticle size controlled by thermal
      evaporation. Large area mapping reveals good uniformity for commercial Aspen
      paper coated with black laser printer ink. A demonstration of the forensic and
      chemical analysis potential in 2-D is shown by uncovering the hidden CsF initials
      made with mineral oil on the coated Aspen paper. The method promises to
      revolutionize nanoscale characterization and industrial monitoring as well as
      chemical analyses by allowing rapid contact angle measurements over large areas
      or large numbers of samples in ways and times that have not been possible before.

PMID- 29041521
TI  - High-acceptance versatile microfocus module based on elliptical Fresnel zone
      plates for small-angle X-ray scattering.
AB  - High-efficiency microfocusing of multi-keV X-rays at synchrotron sources is
      highly profitable for spatially resolved structural analysis of many kinds.
      Because radiation from synchrotron sources is typically elongated along the
      horizontal dimension, generating a microbeam that is isotropic in size requires a
      carefully designed optics system. Here we report on using a combination of a
      horizontally tunable slit downstream of the undulator source with elliptical
      diffractive Fresnel zone plates. We demonstrate the arrangement in context of
      small-angle X-ray scattering experiments, obtaining a microbeam of 2.2 MUm * 1.8
      MUm (X * Y) with a flux of 1.2 * 1010 photons/s at an energy of 11.2 keV at the
      sample position.

PMID- 29041522
TI  - OAM interferometry: the detection of the rotational Doppler shift.
AB  - In this paper, we propose a new type of rotational Doppler shift measurement
      based on the OAM of light which is capable of measuring the rotation of a point
      source in the plane orthogonal to the observer line of sight. By analysing the
      correlations between OAM states of light emitted by rotating sources, the
      rotational Doppler shift, and hence the rate of rotation, can be measured. We
      demonstrate that an OAM interferometer capable of extracting the rotational
      Doppler shift from OAM correlations can be constructed from a standard OAM
      modesorter combined with a phase filter.

PMID- 29041523
TI  - Generation of 300 nm bandwidth 0.5 mJ pulses near 1 MUm in a single stage gas
      filled hollow core fiber.
AB  - A simple and compact spectral-broadening system is presented that is based on a
      single-stage statically pressurized Ar filled hollow core fiber. By optimizing
      the inner diameter of the hollow core fiber, a bandwidth of 300 nm is obtained.
      This is the broadest bandwidth known to date with millijoule level energy near
      the 1-MUm wavelength by a single stage gas filled hollow core fiber.

PMID- 29041524
TI  - Mode-locking evolution in ring fiber lasers with tunable repetition rate.
AB  - We have applied a simple approach to analyze behavior of the harmonically mode
      locked fiber laser incorporating an adjustable Mach-Zehnder interferometer (MZI).
      Our model is able to describe key features of the laser outputs and explore
      limitations of physical mechanisms responsible for laser operation at different
      pulse repetition rates tuned over a whole GHz range. At low repetition rates the
      laser operates as a harmonically mode-locked soliton laser triggered by a fast
      saturable absorber. At high repetition rates the laser mode-locking occurs due to
      dissipative four-wave mixing seeded by MZI and gain spectrum filtering. However,
      the laser stability in this regime is rather low due to poor mode selectivity
      provided by MZI that is able to support the desired laser operation just near the
      lasing threshold. The use of a double MZI instead of a single MZI could improve
      the laser stability and extends the range of the laser tunability. The model
      predicts a gap between two repetitive rate ranges where pulse train generation is
      not supported.

PMID- 29041525
TI  - Metallic planar lens constructed by double-turn waveguides for sub-diffraction
      limit focusing.
AB  - We present a conceptual demonstration of a metallic planar lens composed of
      double-turn waveguides for sub-diffraction-limit focusing. The phase delay of a
      single double-turn waveguide dependent on its structural parameters is
      investigated by employing the finite-difference time-domain (FDTD) numerical
      method. The design utilizes the surface plasmon polaritons (SPPs) that propagate
      along the metal-insulator-metal (MIM) waveguides to achieve the desired spatial
      phase modulation in the transmitted field. The simulated focal length achieved is
      in positive agreement with the design and the full-width at half-maximum (FWHM)
      is 0.446lambda, well beyond the diffraction limit. This superfocusing performance
      can be maintained very well under the slight change of film thickness and slit
      width, showing the robustness of the design. The maximum aspect ratio of
      nanoslits constructing the proposed lens is 3.33, which is far less than the
      previous reports, alleviating the later fabrication. The metallic planar lens as
      demonstrated will find its applications in such fields as lithography, integrated
      optics, and super-resolution imaging.

PMID- 29041526
TI  - Scattering pulse-induced temporal contrast degradation in chirped-pulse
      amplification lasers.
AB  - Herein, a theory for modeling the problem of scattering pulse-induced temporal
      contrast degradation in chirped-pulse amplification (CPA) lasers is introduced.
      Using this model, the temporal evolutions of the scattering and signal pulses
      were simulated, the temporal contrasts for different cases were compared, and
      finally the theoretical prediction was verified by an experimental demonstration.
      The result shows that the picosecond and the nanosecond temporal contrast is
      mainly determined by the scattering pulses generated in the stretcher and the
      compressor, respectively. In addition, the B-integral accumulation will further
      degrade the temporal contrast, especially the picosecond temporal contrast. We
      believe it is helpful for solving the problem of the picosecond pedestal contrast
      (i.e., noise limit). With reference to these results, some suggestions for the
      temporal contrast improvement are presented.

PMID- 29041527
TI  - Polarization independent optical injection locking for carrier recovery in
      optical communication systems.
AB  - An optical injection locking (IL) system that is independent of the incoming
      signal's polarization is demonstrated for carrier recovery in coherent optical
      communication systems. A sub-system that enables polarization independence is
      discussed and experimentally verified. The system is tested over a 20-km test
      field link using a broad-linewidth laser (40 MHz), and shows the suppression of
      phase noise when using the carrier recovered by injection locking as the local
      oscillator.

PMID- 29041528
TI  - 1.024 Tb/s wavelength conversion in a silicon waveguide with reverse-biased p-i-n
      junction.
AB  - We experimentally show an all-optical wavelength conversion of 8 * 32-GBd single
      polarization 16QAM signals using a silicon nano-rib waveguide. The application of
      reverse biasing of the p-i-n junction of the waveguide allows a conversion
      efficiency of -8.5 dB with a measured 3-dB optical bandwidth of about 40 nm.
      Using digital coherent reception, it is shown that the receiver optical signal-to
      noise ratio penalty, at a bit-error ratio of 1 * 10-3, of the wavelength
      converted signals over all eight channels was less than 0.6 dB with reference to
      their respective back-to-back signal channels.

PMID- 29041529
TI  - Propagation effects in the generation process of high-order vortex harmonics.
AB  - We numerically study the propagation of a Laguerre-Gaussian beam through polar
      molecular media via the exact solution of full-wave Maxwell-Bloch equations where
      the rotating-wave and slowly-varying-envelope approximations are not included. It
      is found that beyond the coexistence of odd-order and even-order vortex harmonics
      due to inversion asymmetry of the system, the light propagation effect results in
      the intensity enhancement of a high-order vortex harmonics. Moreover, the orbital
      momentum successfully transfers from the fundamental laser driver to the vortex
      harmonics which topological charger number is directly proportional to its order.

PMID- 29041530
TI  - Experimental demonstration of fronthaul flexibility for enhanced CoMP service in
      5G radio and optical access networks.
AB  - The RAN architecture towards mobile 5G and beyond is undergoing a fundamental
      evolution, which brings optics into the radio world. Fronthaul is a new segment
      that leverages on the advantages of optical communication for RAN transport.
      However, the current fronthaul architecture shows a fixed connection between an
      RRH and a BBU, which leads to inefficient resource utilization. In this paper, we
      focus on the fronthaul flexibility that allows "any-RRH to any-BBU" connection.
      In particular, we consider a CoMP service and discuss how flexible optical
      fronthaul helps to improve its performance. To achieve this goal, we propose an
      SDN-enabled orchestration for coordinating radio and optical access networks.
      Under this unified control manner, the agile RRH-BBU mapping can be reached
      through lightpath reconfiguration. To further verify the benefits of flexibility,
      we experiment the CoMP service in the cloud radio over flexible optical fronthaul
      (CRoFlex) testbed. Experimental results demonstrate the proposed SDN-enabled
      flexible optical fronthaul can improve the CoMP performance by optimizing the RRH
      BBU mapping.

PMID- 29041531
TI  - Ultrawideband optical cancellation of RF interference with phase change.
AB  - This work proposes a novel approach to perform optical cancellation of RF
      interference with any constant phase change, based on polarization-modulator
      based microwave photonic phase shifters. Preliminary results validate the
      proposed scheme and achieve a 30-dB cancellation depth over 9.5 GHz. The
      frequency independent microwave photonic phase shifters also allow for wide
      frequency range tunability towards 30 GHz, and recovery of a signal from a
      wideband interferer. The experimental results are limited by the imperfection of
      the electrical components. The proposed cancellation scheme might not only be
      applicable for WLANs based on standards such as IEEE 802.11ad and 802.11aj, but
      also provide a straight forward solution to the multipath effect.

PMID- 29041532
TI  - Polarized fiber optical parametric amplification in randomly birefringent fibers:
      erratum.
AB  - We correct the value of coefficient Gamma presented in Opt. Express23, 32747
      (2015)10.1364/OE.23.032747, which describes the relationship between the mean
      output degree of polarization and the average gain of fiber optical parametric
      amplifiers.

PMID- 29041533
TI  - Energy-efficient multidimensional Hellinger modulation for SPAD-based optical
      wireless communications.
AB  - Recently, the single photon avalanche diode optical wireless communication (SPAD
      OWC) has attracted much attention due to its potential underwater applications.
      For such system, the channel noise is additive Poisson noise (APN) rather than
      the commonly encountered additive white Gaussian noise (AWGN) and the
      corresponding maximum likelihood (ML) detection is hard to provide a useful
      insight into energy-efficient signal design. By using the previously proposed
      Hellinger distance design criterion, we design an energy-efficient multi
      dimensional constellation within the nonnegative integer set by minimizing the
      average optical power for a fixed minimum Hellinger distance. Comprehensive
      simulations indicate that our designed constellation can substantially outperform
      the currently available pulse amplitude modulation (PAM) and squared PAM for SPAD
      OWC systems.

PMID- 29041534
TI  - Application of third-order correlation between intensity fluctuations to
      determination of scattering potential of quasi-homogeneous medium.
AB  - Within the first-order Born approximation, we introduce the third-order
      correlation between intensity fluctuation (CIF) of light scattered from a quasi
      homogeneous (QH) medium. By utilizing the Gaussian moment theorem for describing
      the scattering potential statistics, analytic forms are derived for the third
      order, normalized CIF and variance of intensity fluctuations (VIF) of the far
      zone scattered field. It is found that the normalized CIF of the scattered field
      is proportional to the product of Fourier transforms of the strengths of the
      scattering potential, while the variance of intensity fluctuations (VIF) of the
      scattered field is the cube of the Fourier transform of the normalized
      correlation coefficient (NCC) of the scattering potential. Based on the derived
      formulas, we show that the correlation function of the scattering potential of
      the medium can be determined from the scattering equations where the third-order
      CIF properties of the scattered field must be known in advance.

PMID- 29041535
TI  - Mitigating the effects of the gain-dependence of the Brillouin line-shape on
      dynamic BOTDA sensing methods.
AB  - It has been recently shown that in stimulated Brillouin amplification (pulsed
      pump & CW probe) the line-shape of the normalized logarithmic Brillouin Gain
      Spectrum (BGS) broadens with increasing gain. Most pronounced for short pump
      pulses, a linewidth increase of ~3 MHz (~1.5 MHz) per dB of additional gain was
      observed for a pump pulse width of 15 ns (30 ns), respectively. This gain
      dependency of the shape of the BGS compromises the accuracy of the otherwise
      attractive, highly dynamic and distributed slope-assisted BOTDA techniques, where
      measurand-induced gain variations of a single probe, are converted to
      strain/temperature values through a calibration factor that depends on the line
      shape of the BGS. A previously developed technique with built-in compensation for
      Brillouin gain variations, namely: the Ratio Double Slope-Assisted BOTDA (RDSA
      BOTDA) method, where both slopes of the BGS are interrogated, fails to meet this
      new challenge of the gain-induced shape dependence of the BGS, resulting, for
      instance, in significant measurement errors of ~5% per dB of gain change for a 15
      ns pump pulse. Here, we propose and demonstrate an extension of the RDSA-BOTDA
      method, which now offers immunity also to Brillouin gain-dependent line-shape
      variations. Requiring a prior characterization of the gain-induced line-shape
      dependency of the fiber and pump-pulse-width in use, this mitigation technique
      takes advantage of the fact that the sum of the measured logarithmic gains at
      judiciously chosen two fixed frequency points of the BGS can be used to determine
      the local peak gain, via a pre-established calibration curve. Based on the
      deduced correct peak gain, its associated BGS shape can now be used in the
      application of the previously introduced RDSA-BOTDA technique to obtain error
      free results, independent of the gain dependence of the line-shape. The proposed
      technique has been successfully put to test in an experiment, involving a RDSA
      BOTDA measurement of a fiber segment, vibrating at 50 Hz with a constant, peak-to
      peak amplitude of 640 microstrain. As the Brillouin gain was manually varied from
      1 to 3.5 dB, classical data processing, based on a single gain value, predicted
      amplitudes which varied by as much as 90 microstrain, while the proposed
      mitigation technique produced the correct constant amplitude, regardless of the
      gain changes. This restored accuracy of the RDSA-BOTDA technique is of
      importance, especially for monitoring real-world dynamic scenarios, where high
      Brillouin gains, which often locally vary due to dynamically introduced losses,
      can successfully achieve fast gain-independent double-slope-assisted Brillouin
      measurements (many kHz's of sampling rates over hundreds of meters), with
      enhanced spatial resolution and signal to noise ratio.

PMID- 29041536
TI  - Nonlinear beam self-cleaning in a coupled cavity composite laser based on
      multimode fiber.
AB  - We study a coupled cavity laser configuration where a passively Q-switched Nd:YAG
      microchip laser is combined with an extended cavity, including a doped multimode
      fiber. For appropriate coupling levels with the extended cavity, we observed that
      beam self-cleaning was induced in the multimode fiber thanks to nonlinear modal
      coupling, leading to a quasi-single mode laser output. In the regime of beam self
      cleaning, laser pulse duration was reduced from 525 to 225 ps. We also observed a
      Q-switched mode-locked operation, where spatial self-cleaning was accompanied by
      far-detuned nonlinear frequency conversion in the active multimode fiber.

PMID- 29041537
TI  - Accurate and spectral efficient channel estimation using inter-block precoding
      and superimposed pilots in optical OFDM systems.
AB  - A new inter-block precoding-based channel estimation (CE) scheme is proposed and
      experimentally demonstrated in an optical OFDM system with a superimposed pilot
      (SP). The proposed inter-block precoding scheme targets on eliminating the
      statistical mean of the unknown data symbols, and thereby improves the
      performance of SP-aided CE. We investigate the impact that both the precoding
      matrix and SP have on the system performance, from which we obtain the optimum
      value of signal-to-pilot power ratio (SPR) as well as the block length. We show
      through simulations and experiments that the proposed CE scheme, in comparison
      with the conventional preamble based scheme, has the advantage of entailing a
      much smaller overhead size, while offering similar performance in terms of CE
      accuracy and bit-error ratio (BER) performances. Furthermore, the proposed
      precoding scheme has no limit to the design of SP, and thus is applicable for any
      periodic pilots.

PMID- 29041538
TI  - Optimal polarization modulation for orthogonal two-axis Lloyd's mirror
      interference lithography.
AB  - Polarization control is of vital importance in two-axis Lloyd's mirror
      interference lithography to achieve the preferred interference fringes. In this
      work, we first establish a three-dimensional polarization ray-tracing model to
      trace the evolution of polarization states of incident beams through the corner
      cube-like interferometer unit of an orthogonal two-axis Lloyd's mirror
      interferometer. With the established model, we then derive the optimal
      combination of initial polarization directions of the incident beams according to
      the orthogonality of polarization states and the contrast of interference
      fringes. The comparison between the simulated and experimental interference
      fringes obtained under different combinations of initial polarization states of
      incident beams verify the feasibility of the established model and the achieved
      optimal polarization modulation.

PMID- 29041539
TI  - Universal phase-only spatial light modulators.
AB  - Universal phase-only spatial light modulators (UP-SLMs) are proposed and
      demonstrated by simulation and experiment. UP-SLMs, which consist of unitarily
      coupled electrically controllable wave plates, convert the optically anisotropic
      properties of the paired two wave plates into an effective single isotropic phase
      plate and can be realized with electrically tunable birefringence materials such
      as uniaxial liquid crystals (LCs). The universal approaches are applicable to any
      uniaxial anisotropic materials based cells, any LC cell operation modes and any
      incident light polarization states. Further the UP-SLMs are experimentally
      demonstrated even with commercial LCD panels having low geometrical rotational
      symmetry. These UP-SLMs will play significant roles in wave optics,
      communications, information displays, digital holography, quantum optics and
      quantum information technology by harnessing their unique capacity of modulating
      the only phase of linearly, circularly, elliptically, azimuthally, radially and
      even randomly polarized light.

PMID- 29041540
TI  - Theoretical guideline for generation of an ultralong magnetization needle and a
      super-long conveyed spherical magnetization chain.
AB  - Considering an azimuthally polarized vortex beam with a Gaussian annulus as an
      incoming light, light induced magnetization fields for both a single high NA lens
      and a pair of high NA lenses are investigated theoretically. We deduce analytical
      formulas for the parameters of a magnetization needle and a magnetization chain
      when the angular width of the incident beam is far less than its central angular
      position. Through these analytical formulas, the properties of the magnetization
      needle and the magnetization chain are very clear and distinct. Compared with
      parameter optimizing to produce an ultralong magnetization needle with lateral
      sub-wavelength scale and a super-long spherical magnetization chain with three
      dimensional super resolution, the analytical method is direct and has a
      theoretical guideline. The validity of these formulas is proved, compared to
      numerical solutions. The present work regarding these super-resolution
      magnetization patterns is of great value in high density all-optical magnetic
      recording, atomic trapping as well as confocal and magnetic resonance microscopy.

PMID- 29041541
TI  - Electrically optofluidic zoom system with a large zoom range and high-resolution
      image.
AB  - We report an electrically controlled optofluidic zoom system which can achieve a
      large continuous zoom change and high-resolution image. The zoom system consists
      of an optofluidic zoom objective and a switchable light path which are controlled
      by two liquid optical shutters. The proposed zoom system can achieve a large
      tunable focal length range from 36mm to 92mm. And in this tuning range, the zoom
      system can correct aberrations dynamically, thus the image resolution is high.
      Due to large zoom range, the proposed imaging system incorporates both camera
      configuration and telescope configuration into one system. In addition, the whole
      system is electrically controlled by three electrowetting liquid lenses and two
      liquid optical shutters, therefore, the proposed system is very compact and free
      of mechanical moving parts. The proposed zoom system has potential to take place
      of conventional zoom systems.

PMID- 29041542
TI  - Profilometry with digital fringe-projection at the spatial and temporal Nyquist
      frequencies.
AB  - A phase-demodulation method for digital fringe-projection profilometry using the
      spatial and temporal Nyquist frequencies is presented. It allows to digitize
      tridimensional surfaces using the highest spatial frequency (pi radians per
      pixel) and consequently with the highest sensitivity for a given digital fringe
      projector. Working with the highest temporal frequency (pi radians per temporal
      sample), the proposed method rejects the DC component and all even-order
      distorting harmonics using 2-step phase shifting; this robustness against
      harmonics is similar to that of the popular 4-step least-squares phase-shifting
      algorithm. The proposed phase-demodulation method is suitable for the
      digitization of piecewise continuous surfaces because it does not require spatial
      low-pass filtering. Gamma calibration is also unnecessary because the projected
      fringes are binary, and the harmonics produced by the binary profile can be
      attenuated with a slight defocusing on the digital projector. Viability of the
      proposed method is supported by experimental results showing complete agreement
      with the predicted behavior.

PMID- 29041543
TI  - Filamentary plasma grating induced by interference of two femtosecond laser
      pulses in water.
AB  - We present direct observation of filamentary plasma grating induced by
      interference between two noncollinear infrared femtosecond pulses in water by
      doping with gold nanoparticles. The gold nanoparticles act as scattering media in
      water and visualize the fine structure of local optical fields of plasma grating.
      By measuring the variation of local conductivity as laser undergoes filamentation
      in water, the generated electron density in water is qualitatively studied.
      Significant enhancement of local electron density is observed at the intersecting
      region as two laser beams form plasma grating, indicating the breakthrough of
      clamped intensity of a conventional filament in water.

PMID- 29041544
TI  - Fiber taper characterization by optical backscattering reflectometry.
AB  - Fiber tapers provide a way to rapidly measure the spectra of many types of
      optical microcavities. Proper fabrication of the taper ensures that its width
      varies sufficiently slowly (adiabatically) along the length of the taper so as to
      maintain single spatial mode propagation. This is usually accomplished by
      monitoring the spectral transmission through the taper. In addition to this
      characterization method it is also helpful to know the taper width versus length.
      By developing a model of optical backscattering within the fiber taper, it is
      possible to use backscatter measurements to characterize the taper width versus
      length. The model uses the concept of a local taper numerical aperture to
      accurately account for varying backscatter collection along the length of the
      taper. In addition to taper profile information, the backscatter reflectometry
      method delineates locations along the taper where fluctuations in fiber core
      refractive index, cladding refractive index, and taper surface roughness each
      provide the dominant source of backscattering. Rayleigh backscattering
      coefficients are also extracted by fitting the data with the model and are
      consistent with the fiber manufacturer's datasheet. The optical backscattering
      reflectometer is also used to observe defects resulting from microcracks and
      surface contamination. All of this information can be obtained before the taper
      is removed from its fabrication apparatus. The backscattering method should also
      be prove useful for characterization of nanofibers.

PMID- 29041545
TI  - Planar two-groove optical differentiator in a slab waveguide.
AB  - We propose a simple planar optical differentiator consisting of two grooves on
      the surface of a slab waveguide. The studied differentiator operates in
      reflection and enables temporal and spatial differentiation of optical pulses and
      beams propagating in the waveguide. The differentiation is associated with the
      excitation of an eigenmode localized at the ridge located between the grooves.
      The presented numerical simulation results demonstrate high-quality spatial,
      temporal and the so-called spatiotemporal differentiation. The proposed
      differentiator may find application in ultrafast analog computing and signal
      processing systems.

PMID- 29041546
TI  - Power laws for backscattering by ice crystals of cirrus clouds.
AB  - The backscattering Mueller matrix for the typical shapes of ice crystals of
      cirrus (hexagonal columns and plates, bullets and droxtals) in the case of their
      random orientations has been approximately presented as the power functions of
      the crystal size from 10 um to 1000 um. The coefficients of the power functions
      have been found. Four commonly used backscatter ratios used in lidar research
      (depolarization, lidar, color and backscatter-to-IWC ratios) have been calculated
      for the first time as the functions of the modal crystal size at the conventional
      lidar wavelengths of 0.355, 0.532 and 1.064 um.

PMID- 29041547
TI  - Few-mode fiber, splice and SDM component characterization by spatially-diverse
      optical vector network analysis.
AB  - This paper discusses spatially diverse optical vector network analysis for space
      division multiplexing (SDM) component and system characterization, which is
      becoming essential as SDM is widely considered to increase the capacity of
      optical communication systems. Characterization of a 108-channel photonic lantern
      spatial multiplexer, coupled to a 36-core 3-mode fiber, is experimentally
      demonstrated, extracting the full impulse response and complex transfer function
      matrices as well as insertion loss (IL) and mode-dependent loss (MDL) data.
      Moreover, the mode-mixing behavior of fiber splices in the few-mode multi-core
      fiber and their impact on system IL and MDL are analyzed, finding splices to
      cause significant mode-mixing and to be non-negligible in system capacity
      analysis.

PMID- 29041548
TI  - Extending chip-based Kerr-comb to visible spectrum by dispersive wave
      engineering.
AB  - Anomalous group velocity dispersion is a key parameter for generating bright
      solitons, and thus wideband Kerr frequency combs. Extension of the frequency
      combs spectrum to visible wavelengths has been a major challenge because of the
      strong normal dispersion of conventional photonic materials at these wavelengths.
      In this paper, we numerically demonstrate a wideband frequency comb extending
      from near-infrared to visible wavelengths (~1200 nm to 650 nm). The proposed
      frequency comb micro-resonator takes advantage of a wideband blue-shifted
      anomalous dispersion, achieved in an optimized over-etched silicon nitride
      waveguide and strong power transfer to shorter wavelengths through radiative
      dispersive waves, achieved by modulating the dispersion in a coupled resonator
      architecture. We show the possibility of obtaining a close to visible dispersive
      Cherenkov radiation peak that is only 10 dB below the overall comb peak and can
      be tuned by adjusting the coupling structure in the coupled resonator
      architecture.

PMID- 29041549
TI  - High Q-factor with the excitation of anapole modes in dielectric split nanodisk
      arrays.
AB  - The simultaneous realization of high Q-factor resonances and strong near-field
      enhancements around and inside of dielectric nanostructures is important for many
      applications in nanophotonics. However, the incident fields are often confined
      within dielectric nanoparticles, which results in poor optical interactions with
      external environment. Near-field enhancements can be extended outside of
      dielectric nanostructures with proper design, but the Q-factor is often reduced
      caused by additional radiation losses. This paper shows that the obstacles to
      achieve high Q-factor, that is, the radiative losses can be effectively
      suppressed by using dielectric nanodisk arrays, where the Q-factor is about one
      order larger than that of the single disks associated with the nonradiating
      anapole modes and the collective oscillations of the arrays. When the resonance
      energies of the electric dipole mode and the subradiant mode are degenerate with
      each other, the destructive interference produces an effect analogous to
      electromagnetically induced transparency. Furthermore, the Q-factor can be
      extremely enlarged with dielectric split nanodisk arrays, where the present of
      the split gap does not induce additional losses. Instead, the coupling between
      the two interfering modes is modified by adjusting the gap width, which makes it
      possible to achieve high Q-factor and strong near-field enhancements around and
      inside of the split disks simultaneously. It is shown that the Q-factor is
      approaching to 106 when the gap width is about 110 nm, and the near-field
      enhancements around and inside of the split disks are about two orders stronger
      than that of the single disk.

PMID- 29041550
TI  - Asymmetrical polarization-dependent scattering and reflection in a sole cell of
      polymer network-90 degrees  twisted nematic liquid crystals.
AB  - The anisotropically intrinsic scattering and reflection of a sole cell of polymer
      network-90 degrees  twisted nematic liquid crystals (PN-90 degrees  TNLCs)
      without any polarizer are proposed. Light with specifically linear polarizations,
      incident from one direction, can penetrate the PN-90 degrees  TNLCs with applied
      voltage. The polarization direction of the output beam will be rotated 90 degrees
      . The same linearly polarized light, incident from the other direction, will be
      scattered because it encounters the refractive indices mismatch of various LC
      domains. The reflection, resulting from the boundaries of LCs and polymers, also
      shows optical anisotropy. Such LC devices can be applied as scattering-type
      linear polarizers.

PMID- 29041551
TI  - Mid-wave infrared beam steering based on high-efficiency liquid crystal
      diffractive waveplates.
AB  - We demonstrated two liquid crystal diffractive waveplates: one optimized for near
      infrared (1.06 um), and another for mid-wave infrared (MWIR, 3~5 um). By
      employing a low loss liquid crystal mixture UCF-M3, whose absorption loss is
      below 2% in the 4~5 um spectral region, the grating achieves over 98% diffraction
      efficiency in a broad MWIR range. To switch the grating, both active and passive
      driving methods can be considered. In our experiment, we used a polymer
      stabilized twisted nematic cell as the polarization rotator for passive driving.
      The obtained rise time is 0.2 ms and decay time is 10 ms.

PMID- 29041552
TI  - Comparison of tool feed influence in CNC polishing between a novel circular
      random path and other pseudo-random paths.
AB  - A new category of circular pseudo-random paths is proposed in order to suppress
      repetitive patterns and improve surface waviness on ultra-precision polished
      surfaces. Random paths in prior research had many corners, therefore deceleration
      of the polishing tool affected the surface waviness. The new random path can
      suppress velocity changes of the polishing tool and thus restrict degradation of
      the surface waviness, making it suitable for applications with stringent mid
      spatial-frequency requirements such as photomask blanks for EUV lithography.

PMID- 29041553
TI  - Orthogonal polarization encoding for reduction of interpixel cross talk in
      holographic data storage.
AB  - Interpixel cross talk decreases the quality of a reconstructed signal in
      holographic data storage and imposes a limitation on its storage capacity. To
      reduce the interpixel cross talk, an orthogonal polarization encoding method is
      proposed. In the proposed method, the polarization state of each pixel is set to
      be orthogonal with that of surrounding pixels. This prevents the interference
      between nearest-neighboring pixels and significantly reduces the gross of the
      interpixel cross talk. The quality of the data page obtained with the proposed
      method is numerically and experimentally evaluated. Those results suggest that
      the proposed method can improve the quality of a reconstructed signal.

PMID- 29041554
TI  - Optical design, laboratory test, and calibration of airborne long wave infrared
      imaging spectrometer.
AB  - We discuss and evaluate a long wave infrared imaging spectrometer in terms of its
      opto-mechanical design and analysis, alignment, testing, and calibration. The
      instrument is a practical airborne sensor achieving high spectral resolution and
      sensitive noise equivalent delta temperature. The instrument operates in the 8 to
      12.5 MUm spectral region with 28.85 nm spectral sampling, 1 mrad instantaneous
      field of view, and >40 degrees  cross track field. The instrument comprises three
      uniform sub-modules with identical design parameters and performances. The sub
      module design is based on a refractive foreoptics feeding an all-reflective
      spectrometer. The optical form of the spectrometer is a double-pass reflective
      triplet with a flat grating, which has a fast f/2 and high optical throughput.
      Cryogenic optics of 100 K is implemented only for the spectrometer. Assembly and
      thermal deformation and focusing adjustment design are particularly considered
      for this low temperature. All the mirrors of the spectrometer are opto-mechanical
      integrated designed and manufactured by single-point diamond turning technology.
      We consider the center sub-module as an example, and we present its laboratory
      testing results and calibration; the results indicate the instrument's potential
      value in airborne sensing.

PMID- 29041555
TI  - Miniaturized compound refractive X-ray zoom lens.
AB  - We introduce the concept of a miniaturized compound refractive X-ray zoom lens
      consisting of SU-8 lenses fabricated by deep X-ray lithography. The focal length
      can be varied by changing the number of lens elements placed in the beam. We use
      suitable actuators to move single lens elements reversibly out of the beam. The X
      ray zoom lens can accept different X-ray energies while keeping a fixed working
      distance, or vary the focal distance for a fixed energy. The latter is useful in
      tuning the magnification factor in full field microscopy.

PMID- 29041556
TI  - Guiding light in a water core all-solid cladding photonic band gap fiber - an
      innovative platform for fiber-based optofluidics.
AB  - We present a single-channel photonic band gap fiber design allowing for guiding
      light inside a water core, which is surrounded by solid microstructured cladding,
      consisting of an array of high refractive index strands in silica. We address all
      relevant properties and show that the microstructure substantially reduces loss.
      We also introduce a ray reflection model, matching numerical modelling and
      allowing for time-effective large-scale parameter sweeps. Our single channel
      fiber concept is particularly valuable for applications demanding fast and
      reliable injection of liquids into the core, with potential impact in fields such
      as optofluidics, spectroscopy or bioanalytics.

PMID- 29041557
TI  - Fabrication and application of a non-contact double-tapered optical fiber
      tweezers.
AB  - A double-tapered optical fiber tweezers (DOFTs) was fabricated by a chemical
      etching called interfacial layer etching. In this method, the second taper angle
      (STA) of DOFTs can be controlled easily by the interfacial layer etching time.
      Application of the DOFTs to the optical trapping of the yeast cells was
      presented. Effects of the STA on the axile trapping efficiency and the trapping
      position were investigated experimentally and theoretically. The experimental
      results are good agreement with the theoretical ones. The results demonstrated
      that the non-contact capture can be realized for the large STA (e.g. 90 deg) and
      there was an optimal axile trapping efficiency as the STA increasing. In order to
      obtain a more accurate measurement result of the trapping force, a correction
      factor to Stokes drag coefficient was introduced. This work provided a way of
      designing and fabricating an optical fiber tweezers (OFTs) with a high trapping
      efficient or a non-contact capture.

PMID- 29041558
TI  - Feeble object detection of underwater images through LSR with delay loop.
AB  - Feeble object detection is a long-standing problem in vision based underwater
      exploration work. However, because of the complicated light propagation situation
      and high background noise, underwater images are highly degraded. Noise is not
      always detrimental. Logical stochastic resonance (LSR) can be a useful tool for
      amplifying feeble signals by utilizing the constructive interplay of noise and a
      nonlinear system. In the present study, an appropriate LSR structure with a delay
      loop is proposed to process a low-quality underwater image for enhancing the
      vision detection accuracy of underwater feeble objects. Ocean experiments are
      conducted to demonstrate the effectiveness of the proposed structure. We also
      give explicit numerical results to illustrate the relationship between the
      structure of LSR and the correct detection probability. Methods presented in this
      paper are quite general and can thus be potentially extended to other
      applications for obtaining better performance.

PMID- 29041559
TI  - Active intensity noise suppression for a broadband mid-infrared laser source.
AB  - Excess relative intensity noise (RIN) constitutes one of the major limitations of
      most spectroscopic methods involving lasers. Here, we present an active RIN
      suppression scheme for a coherent mid-infrared (MIR) light source (8.4-11 um),
      based on intra-pulse difference frequency generation (DFG). Three different
      stabilization concepts that rely on modulating the intensity of the driving near
      infrared (NIR) pulse train with an acousto-optic modulator are investigated and
      compared. By using the wings of the NIR spectrum to generate the error signal, a
      RIN suppression of the MIR pulse train of up to a factor of 20 was achieved in
      the band between 1 Hz and 100 kHz, resulting in a total integrated RIN of 0.07%.

PMID- 29041560
TI  - Single-photon cesium Rydberg excitation spectroscopy using 318.6-nm UV laser and
      room-temperature vapor cell.
AB  - We demonstrate a single-photon Rydberg excitation spectroscopy of cesium (Cs)
      atoms in a room-temperature vapor cell. Cs atoms are excited directly from 6S1/2
      ground state to nP3/2 (n = 70 - 100) Rydberg states with a 318.6 nm ultraviolet
      (UV) laser, and Rydberg excitation spectra are obtained by transmission
      enhancement of a probe beam resonant to Cs 6S1/2, F = 4 - 6P3/2, F' = 5
      transition as partial population on F = 4 ground state are transferred to Rydberg
      state. Analysis reveals that the observed spectra are velocity-selective
      spectroscopy of Rydberg state, from which the amplitude and linewidth influenced
      by lasers' Rabi frequency have been investigated. Fitting to energies of Cs nP3/2
      (n = 70 -100) states, the determined quantum defect is 3.56671(42). The
      demodulated spectra can also be employed as frequency references to stabilize the
      UV laser frequency to specific Cs Rydberg transition.

PMID- 29041561
TI  - Peak-power scaling of femtosecond Yb:Lu2O3 thin-disk lasers.
AB  - We present a high-peak-power SESAM-modelocked thin-disk laser (TDL) based on the
      gain material Yb-doped lutetia (Yb:Lu2O3), which exceeds a peak-power of 10 MW
      for the first time. We generate pulses as short as 534 fs with an average power
      of 90 W and a peak power of 10.1 MW, and in addition a peak power as high as 12.3
      MW with 616-fs pulses and 82-W average power. The center lasing wavelength is
      1033 nm and the pulse repetition rates are around 10 MHz. We discuss and explain
      the current limitations with numerical models, which show that the current peak
      power is limited in soliton modelocking by the interplay of the gain bandwidth
      and the induced absorption in the SESAM with subsequent thermal lensing effects.
      We use our numerical model which is validated by the current experimental results
      to discuss a possible road map to scale the peak power into the 100-MW regime and
      at the same time reduce the pulse duration further to sub-200 fs. We consider
      Yb:Lu2O3 as currently the most promising gain material for the combination of
      high peak power and short pulse duration in the thin-disk-laser geometry.

PMID- 29041562
TI  - Design of broadband reflective circular polarizer for attosecond pulse in the
      extreme ultraviolet region.
AB  - In this paper, we present a design method of broadband reflective circular
      polarizer (BRCP) in the extreme ultraviolet (EUV) region. By using this method,
      we designed three BRCPs with a 6, 12 and 18 eV bandwidth, respectively. Then, we
      investigated the performances of designed BRCPs in theory. The results indicated
      that the reflected lights of these BRCPs all showed a nearly 100% circular
      polarization degree and considerable circular reflection in their design band. In
      addition, we also studied the origin of high circular polarization degree by
      analyzing the phase shift and the reflectivity ratio between s- and p-polarized
      lights induced by the reflection of BRCPs. Furthermore, the pulse responses of
      BRCPs for attosecond pulses were also investigated. The proposed EUV BRCPs can be
      used for controlling the polarization state of broadband EUV sources, e.g.,
      generating the circularly polarized attosecond pulse by a linearly polarized one.

PMID- 29041563
TI  - Diffraction of partially-coherent light beams by microlens arrays.
AB  - The synthesis method including wave-optics and ray-tracing for the acceleration
      of the simulation of micro-optical systems has been developed. The effects of the
      spatial coherence and randomization of microlens array (MLA) parameters have been
      considered. The method based on coherent states representation for the
      calculation of the optical efficiency of microlens arrays taking into account the
      light source polarization has been developed. Numerical simulations of the
      intensity distributions and spreading angle of a diffracted beam have been
      carried out.

PMID- 29041564
TI  - Analysis of modal crosstalk for communication in turbulent ocean using Lommel
      Gaussian beam.
AB  - We analyze OAM modal crosstalk of a Lommel-Gaussian beam induced by anisotropic
      oceanic turbulence. The theoretical model is constructed to illustrate the
      impacts of turbulence and beam parameters on the received crosstalk probability.
      Turbulence conditions with a larger inner-scale factor, larger anisotropic
      factor, higher dissipation rate of kinetic energy, lower dissipation rate of the
      mean-squared temperature, and smaller temperature-salinity contribution ratio
      usually cause smaller crosstalk. Due to its better immunity to turbulence
      interference, a Lommel-Gaussian beam with a small asymmetry factor, low OAM
      quantum number, optimum waist width, and long wavelength in the transmission
      window is preferable for application. The results are useful to improve OAM
      communication performances in oceanic turbulence.

PMID- 29041565
TI  - Radiance based method for accurate determination of volume scattering parameters
      using GPU-accelerated Monte Carlo.
AB  - Volume scattering is an important effect in different fields, ranging from
      biology to lighting. Models for volume scattering usually rely on parameters that
      are estimated with inverse methods that iteratively fit simulations to
      experimental data. To obtain accurate estimates for these parameters, the
      scattered intensity distribution can be used in such fitting methods. However, it
      has been shown that for samples with long optical path lengths this type of data
      may result in poor parameter estimates. In this work, an inverse procedure is
      proposed that fits to scattered radiance distributions. By taking advantage of
      current generation graphics processing units, the method implemented is
      sufficiently efficient to allow performing an in-depth simulation study on the
      difference between using radiance or intensity distributions to estimate the
      volume scattering parameters of samples. This work shows that for samples with
      moderate optical path lengths, the intensity distribution contains sufficient
      information to accurately estimate the volume scattering properties. However, for
      longer optical path lengths, the descriptive power of the intensity distribution
      is not enough and radiance distribution based methods, such as the inverse method
      proposed, are better suited.

PMID- 29041566
TI  - Topologically protected edge states in graphene plasmonic crystals.
AB  - A two-dimensional graphene plasmonic crystal composed of periodically arranged
      graphene nanodisks is proposed. We show that the band topology effect due to
      inversion symmetry broken in the proposed plasmonic crystals is obtained by
      tuning the chemical potential of graphene nanodisks. Utilizing this kind of
      plasmonic crystal, we constructed N-shaped channels and realized topologically
      edged transmission within the band gap. Furthermore, topologically protected
      exterior boundary propagation, which is immune to backscattering, was also
      achieved by modifying the chemical potential of graphene nanodisks. The proposed
      graphene plasmonic crystals with ultracompact size are subject only to intrinsic
      material loss, which may find potential applications in the fields of topological
      plasmonics and high density nanophotonic integrated systems.

PMID- 29041567
TI  - Optical tomographic reconstruction based on multi-slice wave propagation method.
AB  - In optical tomography, it is challenging to obtain high-quality results for
      complex-structured objects which induce multiple scattering. Nonlinear
      reconstruction methods outperform linear ones in these situations. A promising
      nonlinear method is the approach based on beam propagation method, but its
      accuracy may decrease for complicated structures. In this paper, we describe a
      novel tomographic reconstruction method using multi-slice wave propagation method
      (WPM) as the forward model, which simulates the scattering process more precisely
      but has not been introduced in tomographic reconstruction before. The
      computational model of WPM is presented. To tackle the computational complexity,
      we propose an efficient scheme to compute the transmitted field and its
      derivative. We then use an iterative optimization method to recover the
      quantitative refraction index distribution. We also discuss the influences of the
      parameters in the method and how to determine their values. The experimental
      results demonstrate that this method can address multiple scattering problems and
      provide high accuracy for complex-structured objects.

PMID- 29041568
TI  - Two-dimensional switchable blue phase gratings manufactured by nanosphere
      lithography.
AB  - Switchable two dimensional liquid crystal diffraction gratings are promising
      candidates in beam steering devices, multiplexers and holographic displays. For
      these areas of applications a high degree of integration in optical systems is
      much sought-after. In the context of diffraction gratings this means that the
      angle of diffraction should be rather high, which typically poses a problem as
      the fabrication of small grating periods is challenging. In this paper, we
      propose the use of nanosphere lithography (NSL) for the fabrication of two
      dimensionally structured electrodes with a periodicity of a few micrometers. NSL
      is based on the self-assembly of micro- or nanometer sized spheres into
      monolayers. It allows for easy substrate structuring on wafer scale. The
      manufactured electrode is combined with a liquid crystalline polymer-stabilized
      blue phase, which facilitates sub-millisecond electrical switching of the
      diffraction efficiency at a diffraction angle of 21.4 degrees .

PMID- 29041569
TI  - 11-fs dark pulses generated via coherent absorption in plasmonic metamaterial.
AB  - We demonstrate generation of the shortest reported 11fs dark pulses using the
      coherent absorption process on a plasmonic absorber with a gating pulse. The dark
      pulses appear as a power dip on the envelope of a long carrier pulse and are
      characterized using the cross-correlation technique. The principal difference and
      advantage of our approach in comparison with previously developed laser sources
      of dark pulses is that, in principle, it allows transferring arbitrary pattern of
      bright pulses into a pattern of dark pulses in another optical signal channel.

PMID- 29041570
TI  - Fundamental-mode third harmonic generation in microfibers by pulse-induced quasi
      phase matching.
AB  - A scheme to enhance the fundamental-mode third harmonic generation efficiency in
      microfibers is presented. By introducing an appropriate counter-propagating pulse
      train, large propagation constant mismatch is partly overcome and nonlinear phase
      shifts could be corrected for, thus quasi-phase matching between the fundamental
      pump mode and the fundamental third harmonic mode is achieved, enabling the
      harmonic power to grow along the direction of propagation. Depending on the
      microfiber and pulse parameters, phase matching can enhance the conversion
      efficiency by several orders of magnitude with respect to the non-phase matched
      case. This scheme offers an alternative approach for harmonic generation and
      could potentially be applied to other small core waveguides.

PMID- 29041571
TI  - Segmented Bessel beams.
AB  - We investigate segmented Bessel beams that are created by placing different ring
      apertures behind an axicon that is illuminated with a plane wave. We find an
      analytical estimate to determine the shortest possible beam segment by deriving a
      scale-invariant analytical model using appropriate dimensionless parameters such
      as the wavelength and the axicon angle. This is verified using simulations and
      measurements, which are in good agreement. The size of the ring apertures was
      varied from small aperture sizes in the Frauhofer diffraction limit to larger
      aperture sizes in the classical limit.

PMID- 29041572
TI  - Efficient up-conversion red emission from TiO2:Yb,Er nanocrystals.
AB  - Usually, up-conversion (UC) green emission is easily observed by using rare-earth
      doped fluoride nanocrystals. However, preferential red emission is desired for
      some actual applications especially in biological field. Here, we demonstrated
      that the dominant UC red emission can be realized by preparing TiO2:Yb,Er
      nanocrystals under 980 nm exciation. By controlling the crystal symmetry and size
      via the annealing temperature and Yb3+ ions concentration, the enhanced UC red
      emission is achieved. The multi-photon relaxation and cross-relaxation mechanisms
      may be responsible for the energy transform process and in turn the UC emission.

PMID- 29041573
TI  - Electrically controlled Mie-resonance absorber.
AB  - An electrically controlled metamaterial perfect absorber (MPA) based on Mie
      resonance is demonstrated experimentally and modeled numerically. A ceramic
      dielectric cube is adhered to a specially shaped thin copper film sputtered on a
      quartz plate. By passing direct current (DC) through the film, the temperature of
      the cube can be varied, resulting in changing the cube's permittivity and
      shifting the absorption resonance frequency. The frequency increases on heating
      and the absorption is over 99% throughout the tuning range. This method for
      constructing miniaturized tunable MPAs compares favorably to bulky alternative
      designs. It also provides a versatile route to broaden the absorption bandwidth
      and potentially expand the range of applications such as metasurfaces and
      cloaking devices utilizing nonuniform permittivity absorbers produced by
      temperature gradients.

PMID- 29041574
TI  - Compensation-free broadband entangled photon pair sources.
AB  - Quantum sources that provide broadband biphotons entangled in both polarization
      and time-energy degrees of freedom are a rich quantum resource that finds many
      applications in quantum communication, sensing, and metrology. Creating such a
      source while maintaining high entanglement quality over a broad spectral range is
      a challenge, which conventionally requires various compensation steps to erase
      temporal, spectral, or spatial distinguishabilities. Here, we point out that in
      fact compensation is not always necessary. The key to generate broadband
      polarization-entangled biphotons via type-II spontaneous parametric downcoversion
      (SPDC) without compensation is to use nonlinear materials with sufficiently low
      group birefringence that the biphoton bandwidth becomes dispersion-limited. Most
      nonlinear crystals or waveguides cannot meet this condition, but it is easily met
      in fiber-based systems. We reveal the interplay of group birefringence and
      dispersion on SPDC bandwidth and polarization entanglement quality. We show that
      periodically poled silica fiber (PPSF) is an ideal medium to generate high
      concurrence (>0.977) polarization-entangled photons over a broad spectral range
      (>77nm), directly and without compensation. This is the highest polarization
      entanglement concurrence reported that is maintained over a broad spectral range
      from a compensation-free source.

PMID- 29041575
TI  - Estimation of the turbulence energy dissipation rate in the atmospheric boundary
      layer from measurements of the radial wind velocity by micropulse coherent
      Doppler lidar.
AB  - The accuracy of the method of azimuth structure function for estimation of the
      dissipation rate of the kinetic energy of turbulence from an array of radial
      velocities measured by low-energy micropulse coherent Doppler lidars with conical
      scanning by a probing beam around the vertical axis has been studied numerically.
      The applicability of the method in dependence on the turbulence intensity and the
      signal-to-noise ratio has been determined. The method of azimuth structure
      function was applied for estimation of the turbulent energy dissipation rate from
      radial velocities measured by the lidar in the experiments on the coast of Lake
      Baikal. Two dimensional time-height patterns of the wind turbulence energy
      dissipation rate were obtained. Part of them were obtained in presence of the
      atmospheric internal waves (AIWs) and low-level jet streams. It is observed that
      the wind turbulence in the area occupied by jet streams is very weak. In the
      process of dissipation of AIWs the wind turbulence strength increases.

PMID- 29041576
TI  - Analytical link bandwidth model based square array reception for non-line-of
      sight ultraviolet communication.
AB  - An analytical model is presented firstly in this paper to formulate the link
      bandwidth of non-line-of-sight (NLOS) ultraviolet (UV) channel. The link
      bandwidth is characterized by three geometrical parameters including transmitter
      (Tx) elevation angle, receiver (Rx) field of view (FOV), and transceiver
      separation distance, and further expressed as a closed-form through software
      aided numerical fitting. Comparison with the link bandwidth obtained via a Monte
      Carlo model is done to verify the feasibility of this model. Based on this model,
      we investigate the diversity reception on the NLOS UV communication from a new
      perspective. A spatially squared distributed Rx array is customized for the NLOS
      UV channel. Lower temporal broadening is enabled, leading to a higher link
      bandwidth. Numerical results suggest that over 100% improvement of the link
      bandwidth is predicted by the square array reception and the ratio grows rapidly
      with the narrowing of Tx beam divergence. Therefore, this paper provides a guide
      for link analysis and receiver design for NLOS UV communication.

PMID- 29041577
TI  - Robust hollow-fiber-pigtailed 930 nm femtosecond Nd:fiber laser for volumetric
      two-photon imaging.
AB  - We demonstrate a robust high power 930 nm femtosecond Nd:fiber laser system with
      hollow-core photonic bandgap fiber (HC-PBGF) as the output delivery, which can be
      easily integrated into compact two-photon microscopy system for bio-imaging. The
      whole laser system can deliver up to 17.4 nJ, 220-fs pulses at 930 nm with
      repetition rate of 46 MHz. In this paper, this laser was demonstrated as the
      light source for volumetric imaging of zebrafish blood vessel.

PMID- 29041578
TI  - Fluid jet-array parallel machining of optical microstructure array surfaces.
AB  - Optical microstructure array surfaces such as micro-lens array surface, micro
      groove array surface etc., are being used in more and more optical products,
      depending on its ability to produce a unique or particular performance. The
      geometrical complexity of the optical microstructures array surfaces makes them
      difficult to be fabricated. In this paper, a novel method named fluid jet-array
      parallel machining (FJAPM) is proposed to provide a new way to generate the
      microstructure array surfaces with high productivity. In this process, an array
      of abrasive water jets is pumped out of a nozzle, and each fluid jet
      simultaneously impinges the target surface to implement material removal
      independently. The jet-array nozzle was optimally designed firstly to diminish
      the effect of jet interference based on the experimental investigation on the 2
      Jet nozzles with different jet intervals. The material removal and surface
      generation models were built and validated through the comparison of simulation
      and experimental results of the generation of several kinds of microstructure
      array surfaces. Following that, the effect of some factors in the process was
      discussed, including the fluid pressure, nozzle geometry, tool path, and dwell
      time. The experimental results and analysis prove that FJAPM process is an
      effective way to fabricate the optical microstructure array surface together with
      high productivity.

PMID- 29041579
TI  - 42.3 Tbit/s, 18 Gbaud 64 QAM WDM coherent transmission over 160 km in the C-band
      using an injection-locked homodyne receiver with a spectral efficiency of 9
      bit/s/Hz.
AB  - We demonstrate a 235-channel wavelength division multiplexing (WDM), polarization
      multiplexed (pol-mux) 18-Gbaud 64 QAM coherent transmission of 160 km over the
      full C-band. By applying an injection-locked homodyne detection circuit to WDM
      coherent transmission, we have achieved low noise optical carrier-phase locking
      between transmitted data and a local oscillator over the full C-band range. As a
      result, a potential capacity of 42.3 Tbit/s data with a spectral efficiency of 9
      bit/s/Hz was transmitted.

PMID- 29041580
TI  - Optical reflection and waveguiding of sound by photo-thermally induced barriers.
AB  - Control and manipulation of sound is of critical importance to many different
      scientific and engineering fields, requiring the design of rigid physical
      structures with precise geometries and material properties for the desired
      acoustics. In this work, we demonstrate the ability to manipulate the direction
      and magnitude of sound waves traveling in air using laser light, without the need
      for physical interfaces associated with different materials. Efficient reflection
      of sound waves off of transient, optically generated, abrupt air density barriers
      is demonstrated, with acoustic reflections greater than 25% of the incident
      acoustic wave amplitude. Implementation of multiple barriers, can result in
      complete suppress the transmission of incident acoustic signals as great as 70
      dB. Additionally, shaping the laser beam acoustic waveguides can be generated
      with dramatically reduced transmission losses.

PMID- 29041581
TI  - Spatially localized wavelength-selective absorption in morphology-modulated
      semiconductor nanowires.
AB  - In this study, we proposed morphology-modulated Si nanowires (NWs) with a
      hexagonal cross-section and numerically investigated their resonant optical
      absorption and scattering properties. The calculated absorption and scattering
      efficiency spectra of the NWs exhibited optical resonances that could be
      controlled by tuning the aspect ratio (AR) of the NW cross-sectional shapes. The
      spectra also revealed interesting spectral behaviors including resonant peak
      shifts in the absorption spectrum and asymmetric line shapes in the scattering
      spectrum. To achieve spatially confined and wavelength-selective light
      absorption, we periodically modulated the geometry of the diameter in a single NW
      by combining two different ARs; we call these "diameter-modulated NWs." We
      designed various diameter-modulated NWs with short and long pitch sizes, and we
      observed unique and interesting features in the optical resonance and
      corresponding light absorption spectra such as grating modes and three
      dimensional cavity modes. The proposed diameter-modulated NWs can be promising
      building blocks for the nanoscale localized light absorption and detection in
      compact nanophotonic integrated circuits.

PMID- 29041582
TI  - Wideband microwave phase noise measurement based on photonic-assisted I/Q mixing
      and digital phase demodulation.
AB  - A wideband microwave phase noise measurement system is proposed based on
      quadrature phase demodulation of the mixing components of a signal under test
      (SUT) and its delayed replica. The time delay is introduced by a low-loss optical
      fiber, which can be sufficiently large to achieve a high phase noise measurement
      sensitivity, and the quadrature phase demodulation is achieved by photonic
      assisted in-phase and quadrate (I/Q) mixing together with digital signal
      processing. Thanks to the optoelectronic hybrid quadrature phase demodulation,
      the use of feedback loops, which are usually required in conventional photonic
      delay-line-based phase noise measurement systems, is avoided, and the measurable
      frequency range is expanded. An experiment is implemented. Accurate phase noise
      measurement of SUTs in a frequency range of 5-35 GHz is demonstrated. With a 2-km
      single-mode fiber serving as the photonic delay line, the phase noise floor is as
      low as -131 dBc/Hz at the offset frequency of 10 kHz. The proposed scheme can be
      applied for evaluating the performance of microwave systems using low-phase-noise
      and wideband tunable microwave sources.

PMID- 29041583
TI  - Exploring the self-mode locking and vortex structures of nonplanar elliptical
      modes in selectively end-pumped Nd:YVO4 lasers: manifestation of large fractional
      orbital angular momentum.
AB  - An end-pumped Nd:YVO4 laser under selective pumping is used to excite lasing
      modes with transverse patterns performed to exhibit the characteristics of
      multiple spots arranged on elliptical features near degenerate cavities. The
      spatial distribution of elliptical lasing modes is clearly revealed to be
      localized on the nonplanar ray orbits, so-called nonplanar elliptical modes,
      which possess large fractional orbital angular momentum. Moreover, temporal
      dynamics for the output emission of nonplanar elliptical modes are verified to
      obtain self-mode-locked operation. We further numerically manifest not only the
      influence of radial-asymmetry distributions on the vortex structures of nonplanar
      elliptical modes, but also the vector field of transverse lasing modes altered
      with twisting phase structures in the propagation direction.

PMID- 29041584
TI  - Vector vortex beam generation with dolphin-shaped cell meta-surface.
AB  - We present a dolphin-shaped cell meta-surface, which is a combination of dolphin
      shaped metallic cells and dielectric substrate, for vector vortex beam generation
      with the illumination of linearly polarized light. Surface plasmon polaritons are
      excited at the boundary of the metallic cells, then guided by the metallic
      structures, and finally squeezed to the tips to form highly localized strong
      electromagnetic fields, which generate the intensity of vector vortex beams at z
      component. Synchronously, the abrupt phase change produced by the meta-surface is
      utilized to explain the vortex phase generated by elements. The new kind of
      structure can be utilized for communication, bioscience, and materiality.

PMID- 29041585
TI  - Heisenberg-resolution imaging through a phase-controlled screen.
AB  - We propose a N-photon imaging scheme with the resolution reaching the fundamental
      Heisenberg limit. The key imaging element is a phase-controlled screen which
      introduces synchronous-position N-photon interference, giving rise to enhanced
      resolution that exceeds the well-known Rayleigh resolution limit by a factor of
      N. In the standard wide-field illumination situation, our imaging scheme requires
      an entangled source to illuminate the object. Besides, we show that classical
      light is also applicable to realize this Heisenberg-resolution imaging if a
      scanning-focused-beam illumination is used. Our N-photon imaging scheme is
      practically realizable by using current well-developed technology.

PMID- 29041586
TI  - High-power and highly efficient composite laser with an anti-reflection coated
      layer between a laser crystal and a diamond heat spreader fabricated by room
      temperature bonding.
AB  - We have succeeded in bonding a Nd:YAG crystal and an anti-reflection coated
      diamond crystal to realize a composite laser which minimizes the Fresnel
      reflection loss at the bonded interface for the first time. This newly developed
      composite laser has realized higher output power at higher pump power than a non
      composite Nd:YAG laser while keeping nearly the same slope efficiency.

PMID- 29041587
TI  - Impact of LED transmitters' radiation pattern on received power distribution in a
      generalized indoor VLC system.
AB  - This paper analyzes the received power distribution of a generalized indoor
      visible light communication (VLC) system. The generalization includes: both
      ceiling-mounted and wall-mounted layouts are considered on the transmitting end
      to cover some special scenarios; a generally applicable sum-of-sine luminous
      intensity pattern (SSLIP) is used to fit light emitting diodes (LEDs)' radiation
      curve; the receiver is considered to have a large light receiving area (LRA) with
      non-uniformly distributed received power. Through mathematical calculation, the
      expression of received power at any point of the room is derived. Using the
      expression, the impact of transmitting LEDs' radiation pattern on received power
      performance is investigated. It is suggested that in the ceiling-mounted
      scenario, the LED transmitters with sharp luminous intensity patterns have bigger
      received power variations and shorter optimal receiving distances. In the wall
      mounted case in contrast, sharp luminous intensity patterns lead to smaller
      received power variations and longer optimal receiving distances.

PMID- 29041588
TI  - One-dimensional single-photon position-sensitive silicon photomultiplier and its
      application in Raman spectroscopy.
AB  - We present a one-dimensional (1-D) single-photon position-sensitive silicon
      photomultiplier (PS-SiPM) that can perform both photon number and position
      discriminations. The device, which features epitaxial quenching resistors and a
      continuous cap resistive layer for charge division, possesses two cathodes on top
      and one anode at the bottom. The PS-SiPM shows an active size of 2.2 mm * 2.2 mm
      and micro avalanche photodiode cell pitch of ~10 MUm. The position measurement
      error (PME) and position resolution of the device are analyzed. The PME with low
      mean photoelectron number of approximately 0.11 is 29.6 +/- 27.3 MUm. The single
      photon position resolution is 393.4 MUm. When the photoelectron number increases
      from 1 to 7, the position resolution is improved from 393.4 MUm to 56.2 MUm. The
      application of the PS-SiPM in Raman spectroscopy for carbon tetrachloride (CCl4)
      at room temperature shows advantages of both CCD (rapid measurement) and
      photomultiplier tube (high gain, fast photon response, and simple readout
      electronics). This novel device concept exhibits potential as a low-cost and high
      performance detector for various laser spectroscopies.

PMID- 29041589
TI  - Design of zigzag folded inversion-stacked AlGaAs waveguides for ultra-compact
      wavelength converters.
AB  - We have proposed and designed zigzag-folded U-shaped waveguides to realize highly
      efficient wavelength conversion with an extremely small footprint. Extreme high
      efficiencies are achieved with a combination of modal phase matching and 4- quasi
      phase matching in inversion-stacked AlGaAs/Alox waveguides. Numerical simulations
      reveal that the conversion efficiency of second harmonic generation pumped at
      1.55 MUm as high as 12000 %W-1 can be achieved in an 8.0-mm-long AlGaAs/Alox
      waveguide that is folded up into a small domain of 0.8*0.6 mm2 area. A phase
      matching signal bandwidth of difference frequency generation, 29 nm, covers 83 %
      of the telecommunication C band.

PMID- 29041590
TI  - Photoacoustic imaging in scattering media by combining a correlation matrix
      filter with a time reversal operator.
AB  - Acoustic scattering medium is a fundamental challenge for photoacoustic imaging.
      In this study, we reveal the different coherent properties of the scattering
      photoacoustic waves and the direct photoacoustic waves in a matrix form. Direct
      waves show a particular coherence on the antidiagonals of the matrix, whereas
      scattering waves do not. Based on this property, a correlation matrix filter
      combining with a time reversal operator is proposed to preserve the direct waves
      and recover the image behind a scattering layer. Both numerical simulations and
      photoacoustic imaging experiments demonstrate that the proposed approach
      effectively increases the image contrast and decreases the background speckles in
      a scattering medium. This study might improve the quality of photoacoustic
      imaging in an acoustic scattering environment and extend its applications.

PMID- 29041591
TI  - Optical signal suppression by a cascaded SOA/RSOA for wavelength reusing
      reflective PON upstream transmission.
AB  - An optical signal suppression technique based on a cascaded SOA and RSOA is
      proposed for the reflective passive optical networks (PONs) with wavelength
      division multiplexing (WDM). By suppressing the downstream signal of the optical
      carrier, the proposed reflective PON effectively reuses the downstream optical
      carrier for upstream signal transmission. As an experimental demonstration, we
      show that the proposed optical signal suppression technique is effective in terms
      of the signal bandwidth and bit-error-rate (BER) performance of the remodulated
      upstream transmission.

PMID- 29041592
TI  - Underwater computational ghost imaging.
AB  - Since the quality of underwater classical optical imaging is constrained by the
      absorptive and scattering nature for underwater environment, it is a challenging
      task to obtain long distance imaging. Ghost imaging is a second-order correlation
      imaging method using co-incidence measurement, which has the advantages of
      disturbance-free and wider angle of view (AOV), which can effectively improve the
      imaging result. We have investigated the computational ghost imaging under the
      underwater conditions for different turbidities and from different angles. The
      reconstruction obtained by computational ghost imaging can be rather desirable,
      in the scenarios that the classical optical imaging method completely fails.
      Moreover, the underwater computational ghost imaging can bear a wide range of
      AOV, where the obtained imaging results can be satisfiable in regardless of the
      detector's locations. This result brings a better alternative for underwater
      optical imaging.

PMID- 29041593
TI  - The Berry phase in the nanocrystal complex composed of metal nanoparticle and
      semiconductor quantum dot.
AB  - We investigate the Berry phase in the nanocrystal complex made of a metal
      nanoparticle and a slowly rotating semiconductor quantum dot under the radiation
      of a circularly polarized light. The Berry phase in the dynamic system is found
      to be more effective to manifest the interaction between the plasmon in the metal
      nanoparticle and the exciton in the quantum dot. The dependences of the Berry
      phase on the interparticle distance and the relative position are studied in the
      weak field condition. The methods to observe the Berry phase are also given.

PMID- 29041594
TI  - Time-resolved high harmonic spectroscopy of dynamical symmetry breaking in bi
      circular laser fields: the role of Rydberg states.
AB  - The bi-circular scheme for high harmonic generation, which combines two counter
      rotating circular fields with frequency ratio 2:1, has recently permitted to
      generate high harmonics with essentially circular polarization, opening the way
      for ultrafast chiral studies. This scheme produces harmonic lines at 3N + 1 and
      3N + 2 multiples of the fundamental driving frequency, while the 3N lines are
      forbidden owing to the three-fold symmetry of the field. It is generally
      established that the routinely observed signals at these forbidden harmonic lines
      come from a slight ellipticity in the driving fields, which breaks the three-fold
      symmetry. We find that this is neither the only nor it is the dominant mechanism
      responsible. The forbidden lines can be observed even for perfectly circular,
      long driving pulses. We show that they encode rich information on the sub-cycle
      electronic dynamics that occur during the generation process. By varying the time
      delay and relative intensity between the two drivers, we demonstrate that when
      the second harmonic either precedes or is more intense than the fundamental
      field, the weak effects of dynamical symmetry breaking caused by finite pulse
      duration are amplified by electrons trapped in Rydberg orbits (i.e., Freeman
      resonances), and that the forbidden harmonic lines are a witness of this.

PMID- 29041595
TI  - Highly efficient and broadband optical polarizers based on dielectric nanowires.
AB  - The development of optical materials and devices that mimic the functionalities
      of conventional bulky optical components but on a much smaller footprint remains
      an important priority in nanophotonics. One prominent class of such optical
      elements are polarizers that change the polarization state of incident light.
      Recently, advances in plasmonic and photonic metasurfaces have given rise to
      different classes of subwavelength polarizers. Low efficiency and narrow band of
      operation remain, however, significant challenges. Here, we propose a device
      based on high refractive index dielectric nanowire dimers and analyze its working
      mechanism as efficient and broadband circular polarizers in the optical region of
      the electromagnetic spectrum. Our analysis predicts that a polarization
      conversion of roughly 97% with a transmission efficiency of more than 93% in a
      broad range of the visible spectrum is possible with nanowire dimers.

PMID- 29041596
TI  - Wideband backscattering reduction at terahertz using compound reflection grating.
AB  - Backscattering reduction is usually achieved by using either absorbers or
      diffractions gratings at the expense of a narrow bandwidth. In this paper, we
      propose a different strategy based on a metallic compound reflection grating
      (CRG). We demonstrate that this structure allows a strong and broadband
      (fractional bandwidth, FBW ~57%) backscattering reduction in the terahertz (THz)
      range by efficiently transferring the incident energy to the diffracted modes.
      The design is analyzed in terms of equivalent circuit and numerical simulations
      and the results are corroborated by a manufactured prototype operating at 0.35
      THz.

PMID- 29041597
TI  - Enhanced light emission from improved homogeneity in biaxially suspended
      Germanium membranes from curvature optimization.
AB  - A silicon compatible light source is crucial to develop a fully monolithic
      silicon photonics platform. Strain engineering in suspended Germanium membranes
      has offered a potential route for such a light source. However, biaxial
      structures have suffered from poor optical properties due to unfavorable strain
      distributions. Using a novel geometric approach and finite element modelling
      (FEM) structures with improved strain homogeneity were designed and fabricated.
      Micro-Raman (MU-Raman) spectroscopy was used to determine central strain values.
      Micro-photoluminescence (MU-PL) was used to study the effects of the strain
      profiles on light emission; we report a PL enhancement of up to 3x by optimizing
      curvature at a strain value of 0.5% biaxial strain. This geometric approach
      offers opportunity for enhancing the light emission in Germanium towards
      developing a practical on chip light source.

PMID- 29041598
TI  - Indoor infrared optical wireless localization system with background light power
      estimation capability.
AB  - The indoor user localization function is in high demand for high-speed wireless
      communications, navigations and smart-home applications. The optical wireless
      technology has been used to localize end users in indoor environments. However,
      its accuracy is typically very limited, due to the ambient light, which is
      relatively strong. In this paper, a novel high-localization-accuracy optical
      wireless based indoor localization system, based on the use of the mechanism that
      estimates background light intensity, is proposed. Both theoretical studies and
      demonstration experiments are carried out. Experimental results show that the
      accuracy of the proposed optical wireless indoor localization system is
      independent on the localization light strength, and that an average localization
      error as small as 2.5 cm is attained, which is 80% better than the accuracy of
      previously reported optical wireless indoor localization systems.

PMID- 29041599
TI  - Monolithic optofluidic mode coupler for broadband thermo- and piezo-optical
      characterization of liquids.
AB  - We present a monolithic fiber device that enables investigation of the thermo-
      and piezo-optical properties of liquids using straightforward broadband
      transmission measurements. The device is a directional mode coupler consisting of
      a multi-mode liquid core and a single-mode glass core with pronounced coupling
      resonances whose wavelength strongly depend on the operation temperature. We
      demonstrated the functionality and flexibility of our device for carbon
      disulfide, extending the current knowledge of the thermo-optic coefficient by 200
      nm at 20  degrees C and uniquely for high temperatures. Moreover, our device
      allows measuring the piezo-optic coefficient of carbon disulfide, confirming
      results first obtained by Rontgen in 1891. Finally, we applied our approach to
      obtain the dispersion of the thermo-optic coefficients of benzene and
      tetrachloroethylene between 450 and 800 nm, whereas no data was available for the
      latter so far.

PMID- 29041600
TI  - Analysis of a lens-array modulated coaxial holographic data storage system with
      considering recording dynamics of material.
AB  - In the first time, a simulation model with considering the recording dynamics of
      material is built and is used to simulate evolution of the grating strength of
      the recorded hologram in a coaxial volume holographic memory system. In addition,
      phase modulation by lens array in the reference is introduced and observed to
      perform better diffracted signal quality and higher shifting selectivity, in both
      simulation and experiment. The use of lens array is found to provide multiple
      advantages in volume holographic memory system. The new simulation model
      potentially can be used to precisely design the system to obtain higher
      diffracted signal quality, higher shifting selectivity, and reduction of M#
      consumption and increase of storage capacity.

PMID- 29041601
TI  - Fabrication of diffraction based security elements using direct laser
      interference patterning.
AB  - Product piracy impacts wide areas of the global economy resulting in multi
      billion dollar losses per year. Therefore, product protection technologies are
      required to produce security elements with high flexibility and complexity. In
      this work, the fabrication of diffraction-based security elements, so called
      grating cell arrays, using direct laser interference patterning is presented.
      Ultraviolet two-beam interference patterning is used to structure line-like
      gratings into 80 um in diameter spots with spatial periods ranging from 0.7 um to
      2.2 um on PET substrates. The developed grating cell arrays are generated by the
      combination of several holographic surface gratings with variable spatial period
      and pattern orientation. The stored security information can be visualized by
      illumination with a coherent light source such as a laser pointer.

PMID- 29041602
TI  - Virtual ellipsometry on layered micro-facet surfaces.
AB  - Microfacet-based BRDF models are a common tool to describe light scattering from
      glossy surfaces. Apart from their wide-ranging applications in optics, such
      models also play a significant role in computer graphics for photorealistic
      rendering purposes. In this paper, we mainly investigate the computer graphics
      aspect of this technology, and present a polarisation-aware brute force
      simulation of light interaction with both single and multiple layered micro-facet
      surfaces. Such surface models are commonly used in computer graphics, but the
      resulting BRDF is ultimately often only approximated. Recently, there has been
      work to try to make these approximations more accurate, and to better understand
      the behaviour of existing analytical models. However, these brute force
      verification attempts still emitted the polarisation state of light and, as we
      found out, this renders them prone to mis-estimating the shape of the resulting
      BRDF lobe for some particular material types, such as smooth layered dielectric
      surfaces. For these materials, non-polarising computations can mis-estimate some
      areas of the resulting BRDF shape by up to 23%. But we also identified some other
      material types, such as dielectric layers over rough conductors, for which the
      difference turned out to be almost negligible. The main contribution of our work
      is to clearly demonstrate that the effect of polarisation is important for
      accurate simulation of certain material types, and that there are also other
      common materials for which it can apparently be ignored. As this required a BRDF
      simulator that we could rely on, a secondary contribution is that we went to
      considerable lengths to validate our software. We compare it against a state-of
      art model from graphics, a library from optics, and also against ellipsometric
      measurements of real surface samples.

PMID- 29041603
TI  - MDM transmission of CAP-16 signals over 1.1- km anti-bending trench-assisted
      elliptical-core few-mode fiber in passive optical networks.
AB  - Mode-division multiplexing passive optical network (MDM-PON) is a promising
      scheme for next-generation access networks to further increase the transmission
      capacity and number of end-customers. In this paper, we propose and
      experimentally demonstrate the implementation of MDM-PON architecture with the
      carrier-less amplitude/phase (CAP) modulation signals and two effectively
      separated spatial modes multiplexing transmission in an elliptical-core few-mode
      fiber (EC-FMF). The trench-assisted EC-FMF features favorable anti-bending
      performance with negligible power variations and stable mode intensity profiles
      under extreme bending conditions. Two spatial modes carrying CAP-16 signals for
      four users with net data rate of 5 Gb/s per user in the downstream transmission
      over 1.1-km EC-FMF is demonstrated. The measured mode crosstalk including mode
      (de)multiplexing and 1.1-km EC-FMF transmission is less than -18 dB and multiple
      input multiple output (MIMO) technique is not used in the experiment for
      simplicity. The measured optical signal-to-noise ratio (OSNR) penalties for the
      downstream transmission without or with crosstalk at a bit-error rate (BER) of
      3.8x10-3 (7% forward error correction (FEC) threshold) are less than 1.8 dB and
      3.1 dB, respectively. Larger transmission capacity and more users are expected
      when further employing higher dimension CAP signals and EC-FMF supporting more
      separable spatial modes.

PMID- 29041604
TI  - Optical PAM-4 signal generation using a silicon Mach-Zehnder optical modulator.
AB  - An analytic model is proposed to study the linearity performance of the silicon
      Mach-Zehnder optical modulator. According to the simulation results, we optimize
      the width of the silicon rib waveguide and the location of the PN junction to
      improve the linearity performance. The fabricated silicon Mach-Zehnder optical
      modulator has a spurious free dynamic range of 113.3 dB.Hz2/3 and 88.9 dB.Hz1/2
      for the third-order intermodulation distortion and the second-order harmonic
      distortion. We also demonstrate the optical four-level pulse-amplitude-modulation
      (PAM-4) signal generation through the device. The generated optical PAM-4 signal
      is characterized at the rates up to 35 Gbaud. The BERs of the optical PAM-4
      signals can reach 5.2?10-6 at 20 Gbaud and 6.6?10-5 at 32 Gbaud, which are much
      lower than the threshold of hard decision forward error correction (3.8 ?10-3).

PMID- 29041605
TI  - Quasi-optical frequency selective surface with phase compensation structure
      correcting the beam distortion.
AB  - In space-borne quasi-optical feed system, frequency selective surface (FSS)
      should meet both electrical properties and mechanical requirements. In the paper,
      we design and fabricate three FSSs to achieve these goals. We present a novel FFS
      with phase compensation structure correcting the beam distortion. The phase
      compensation structure consists of short-ended circular waveguide array, inspired
      by the idea of reflect array antenna. The first FSS meets the need of electrical
      performance, however, which is too weak to pass the mechanical test. The second
      one overcomes the former problem, but brings the aberration in reflection beam,
      due to the discontinuity of the reflection phase. The third one with phase
      compensation structure meets all the demands. The insertion phase of the unit
      cell compensates 119 and 183 GHz two reflection bands, reconfigures the field
      distributions on the cross section of beam waist simultaneously. What' more, this
      FSS extends the functionality of the original FSS. To some extent, the FSS with
      phase compensation structure shares the ellipsoidal reflector's pressure to
      adjust the beam.

PMID- 29041606
TI  - Development and performance evaluation of self-absorption-free laser-induced
      breakdown spectroscopy for directly capturing optically thin spectral line and
      realizing accurate chemical composition measurements.
AB  - A novel self-absorption-free laser-induced breakdown spectroscopy (SAF-LIBS)
      technique is proposed to directly capture the optically thin spectral line by
      matching the measured doublet atomic lines intensity ratios with the theoretical
      one. To realize the experimental SAF-LIBS, the integration time, the fiber
      collection angle, and the delay time are optimized. The optically thin conditions
      are validated by comparing the linearity of Boltzmann plots with the traditional
      self-absorption (SA) correction method and evaluating the SA coefficients. The
      applicability and limitation of SAF-LIBS on element concentration and laser
      energy are also discussed. Univariate quantitative analysis results show that,
      compared with ordinary LIBS, the average absolute error of aluminum concentration
      has been reduced by an order of magnitude, which proves that this SAF-LIBS
      technique is qualified to realize accurate chemical composition measurements.

PMID- 29041607
TI  - Efficient second harmonic generation in low-loss planar GaN waveguides.
AB  - We demonstrate low-loss GaN/AlGaN planar waveguides grown by molecular beam
      epitaxy on sapphire substrates. By using a proper AlGaN cladding layer and
      reducing surface roughness we reach <1dB/cm propagation losses at 633nm. These
      low propagation losses allow an efficient second harmonic generation using modal
      phase matching between a TM0 pump at 1260nm and a TM2 second harmonic at 630nm. A
      maximal power conversion of 2% is realized with an efficiency of 0.15%.W-1cm-2.
      We provide a modelling that demonstrates broadband features of GaN/AlGaN platform
      by showing second harmonic wavelengths tunability from the visible up to the near
      infrared spectral region. We discuss drawbacks of modal phase matching and
      propose a novel solution which allows a drastic improvement of modal overlaps
      with the help of a planar polarity inversion. This new approach is compatible
      with low propagation losses and may allow as high as 100%.W-1cm-2 conversion
      efficiencies in the future.

PMID- 29041608
TI  - Improving the resolution and the throughput of spectrometers by a digital
      projection slit.
AB  - The contradiction between spectral resolution and throughput for the optical
      spectrometers is still a problem that needs to be solved. We introduce a simple
      and feasible method of the digital projection slit (DPS), which can improve both
      the spectral resolution and throughput of the optical spectrometer. The DPS
      spectrum is accurate and reliable without using the optical transfer function
      (OTF) of the optical spectrometer. The method has been successfully applied in
      the fiber spectrometer and the Raman spectrometer. The resolution of the
      recovered spectra can be increased by ~3 times and the throughput can be
      increased by ~5 times.

PMID- 29041609
TI  - Optical chirality breaking in a bilayered chiral metamaterial.
AB  - We propose a planar optical bilayered chiral metamaterial, which consists of
      periodic metallic arrays of two L-shaped structures and a nanorod twisted on both
      sides of a dielectric slab, to investigate the optical chirality breaking effect
      by using finite-difference time-domain (FDTD) method. Even the metamaterial is
      with chiral symmetry, an optical chirality breaking window in the asymmetric
      transmission pass band is obtained in chiral metamaterial structure. We analyze
      the plasmonic mode properties and attribute the mechanism of the optical
      chirality breaking effect to the plasmonic analogue of EIT. The optical chirality
      breaking window can be modulated by changing the geometric parameters of the
      nanorods in the structure.

PMID- 29041610
TI  - Continuous axial scanning of a Gaussian beam via beam steering.
AB  - We propose and demonstrate experimentally the transfer of one spatial degree of
      freedom of a laser beam onto another one. Using a multi-plane light conversion
      device (MPLC) and a modal analysis, we designed a passive setup with immediate
      response which couples a displacement and tilt in the transverse plane to a
      longitudinal shift of the focus point of a beam. With this design, we
      demonstrated a shift of the focal point of the output beam by 4 zR along the
      propagation axis.

PMID- 29041611
TI  - Dynamic spontaneous emission control of an optical emitter coupled to plasmons in
      strained graphene.
AB  - Spontaneous emission control of an optical emitter is critical for many
      applications, such as in the fields of sensing, integrated photonics and quantum
      optics. Integrating optical emitters with a mechanical system can provide an
      avenue for strain sensors as well. Here, the dynamic spontaneous emission
      modification of an emitter coupled to graphene by uniaxial strain is
      demonstrated. Our results show that the emission rate can be controlled by tuning
      the strain of graphene, which depends on the polarized orientation of the
      emitter. More specifically, the decay rate can be enhanced for several times if
      the emitter is polarized perpendicular to graphene under strain. Azimuthal angle
      dependent oscillation of decay rate exists for the emitter polarized parallel to
      the graphene. Moreover, the controllable decay of the emitter comes from the
      anisotropic plasmons excitation in strained graphene, which is verified by the
      corresponding isofrequency contours of plasmons. The strain engineering provides
      a new platform for dynamic spontaneous emission modulation of emitters coupled
      with graphene, which opens up intriguing possibilities for the design of strain
      sensors and quantum devices.

PMID- 29041612
TI  - Effect of two-center interference on molecular ionization in multiphoton
      ionization regime.
AB  - Using solution of the full three-dimensional time-dependent Schrodinger equation
      (TDSE) in prolate spheroidal coordinates, we investigate the orientation
      dependence of ionization of H2+ in near-infrared laser fields. It is found that,
      the ionization probability decreases as a function of the alignment angle in
      tunneling ionization regime, while it ascends with the increase of orientation
      angle in multiphoton ionization regime for the internuclear distance R=2 a.u.
      Furthermore, the result obtained by the length gauge strong-field approximation
      theory is in qualitative agreement with that calculated by the TDSE but the
      radiation gauge strong-field approximation and molecular ADK theories fail to
      reproduce the TDSE result. Analysis indicates that the above intriguing feature
      can be ascribed to the interference between the partial electron wave packets
      emitted from different molecular cores, which becomes evident at low laser
      intensity due to increased width of the initial mechanical momentum of the
      photoelectron at ionization moment. In addition, when the internuclear distance
      increases to R=4 a.u., the ionization yields decrease vs alignment angle in both
      tunneling and multiphoton regimes since the electron wavefunction of the 1sigmag
      orbit is more concentrated in the molecular axis than that of R=2 a.u.

PMID- 29041613
TI  - Performance enhanced DDO-OFDM system with adaptively partitioned precoding and
      single sideband modulation.
AB  - As a promising solution for short-to-medium transmission systems, direct
      detection optical orthogonal frequency division multiplexing (DDO-OFDM) or
      discrete multi-tone (DMT) has been intensively investigated in last decade.
      Benefitting from the advantages of peak-to-average power (PAPR) reduction and
      signal-to-noise ratio (SNR) equalization, precoding techniques are widely applied
      to enhance the performance of DDO-OFDM systems. However, the conventional method
      of partitioning precoding sets limits the ability of precoding schemes to
      optimize the SNR variation and the allocation of modulation formats. Thus, the
      precoding transmission systems are hard to reach the capacity that traditional
      bit-power loading (BPL) techniques, like the Levin-Campello (LC) algorithm, can
      achieve. In this paper, we investigate the principle of SNR variation for
      precoded DDO-OFDM systems and theoretically demonstrate that the SNR equalization
      effect of precoding techniques is actually determined by the noise equalization
      process. Based on this fact, we propose an adaptively partitioned precoding (APP)
      algorithm to unlock the ability to control the SNR of each subcarrier. As
      demonstrated by the simulation and experimental results, the proposed APP
      algorithm achieves the transmission capacity as high as the LC algorithm and has
      nearly 1 dB PAPR reduction. Besides, the look-up table (LUT) operation ensures
      low complexity of the proposed APP algorithm compared with LC algorithm. To avoid
      severe chromatic dispersion (CD) induced spectral fading, single sideband (SSB)
      modulation is also implemented. We find that SSB modulation can reach the
      capacity of double sideband (DSB) modulation in optical back-to-back (OB2B)
      configuration by optimizing the modulation index. Therefore, the APP based SSB
      DDO-OFDM scheme can sufficiently enhance the performance of cost-sensitive short
      to-medium reach optical fiber communication systems.

PMID- 29041614
TI  - Fast two-snapshot structured illumination for temporal focusing microscopy with
      enhanced axial resolution.
AB  - We present a new two-snapshot structured light illumination (SLI) reconstruction
      algorithm for fast image acquisition. The new algorithm, which only requires two
      mutually pi phase-shifted raw structured images, is implemented on a custom-built
      temporal focusing fluorescence microscope (TFFM) to enhance its axial resolution
      via a digital micromirror device (DMD). First, the orientation of the modulated
      sinusoidal fringe patterns is automatically identified via spatial frequency
      vector detection. Subsequently, the modulated in-focal-plane images are obtained
      via rotation and subtraction. Lastly, a parallel amplitude demodulation method,
      derived based on Hilbert transform, is applied to complete the decoding
      processes. To demonstrate the new SLI algorithm, a TFFM is custom-constructed,
      where a DMD replaces the generic blazed grating in the system and simultaneously
      functions as a diffraction grating and a programmable binary mask, generating
      arbitrary fringe patterns. The experimental results show promising depth
      discrimination capability with an axial resolution enhancement factor of 1.25,
      which matches well with the theoretical estimation, i.e, 1.27. Imaging
      experiments on pollen grain and mouse kidney samples have been performed. The
      results indicate that the two-snapshot algorithm presents comparable contrast
      reconstruction and optical cross-sectioning capability than those adopting the
      conventional root-mean-square (RMS) reconstruction method. The two-snapshot
      method can be readily applied to any sinusoidally modulated illumination systems
      to realize high-speed 3D imaging as less frames are required for each in-focal
      plane image restoration, i.e., the image acquisition speed is improved by 2.5
      times for any two-photon systems.

PMID- 29041615
TI  - Generation of spatio-temporal extreme events in noise-like pulses NPE mode-locked
      fibre laser.
AB  - We experimentally study spatio-temporal generation of extreme events in the
      radiation of NPE mode-locked fibre laser generating noise-like pulses. We show
      that new pulses starts from high-intensity spatio-temporal structure which
      consist of mainly 3 subsequent pulses which are both separated over fast and slow
      evolution time. Statistical analysis of the noise-like pulse evolution over round
      trips shows that the pulse width and intensity varies with a period of around 85
      round-trips which does not change from pulse to pulse. The intensity probability
      density function has a heavy tail originated only from events of pulse formation.

PMID- 29041616
TI  - Propagation and absorption of light in planar dielectric waveguides with two
      dimensional semiconductors.
AB  - Strong optical responses of atomically thin two-dimensional (2D) semiconductors
      make them attractive candidates for integration into various photonic and
      optoelectronic structures. We discuss some fundamental effects of such
      integration into planar dielectric waveguides by demonstrating that a substantial
      modification of the spectrum of waveguide modes can occur due to high in-plane
      polarizability of 2D layers. Our calculations illustrate both the conceptual
      possibilities associated with sharp excitonic resonances as well as the results
      obtained with the experimentally assessed polarizability of monolayer MoS2 over a
      broad spectral range. We point out that waveguide structures could also enable
      the tunable absorption by 2D semiconductors of the light that propagates along
      them, a modality quite different from the traditional light harvesting geometry.

PMID- 29041617
TI  - Polarization independent subtractive color printing based on ultrathin hexagonal
      nanodisk-nanohole hybrid structure arrays.
AB  - Structural color printing based on plasmonic metasurfaces has been recognized as
      a promising alternative to the conventional dye colorants, though the color
      brightness and polarization tolerance are still a great challenge for practical
      applications. In this work, we report a novel plasmonic metasurface for
      subtractive color printing employing the ultrathin hexagonal nanodisk-nanohole
      hybrid structure arrays. Through both the experimental and numerical
      investigations, the subtractive color thus generated taking advantages of
      extraordinary low transmission (ELT) exhibits high brightness, polarization
      independence and wide color tunability by varying key geometrical parameters. In
      addition, other regular patterns including square, pentagonal and circular shapes
      are also surveyed, and reveal a high color brightness, wide gamut and
      polarization independence as well. These results indicate that the demonstrated
      plasmonic metasurface has various potential applications in high-definition
      displays, high-density optical data storage, imaging and filtering technologies.

PMID- 29041618
TI  - Trade-offs between structural integrity and acquisition time in stochastic super
      resolution microscopy techniques.
AB  - The applicability of widefield stochastic microscopy, such as PALM or STORM, is
      limited by their long acquisition times. Images are produced from the
      accumulation of a large number of frames that each contain a scarce number of
      super-resolved localizations. We show that the random and uneven distribution of
      localizations leads to a specific type of trade-off between the spatial and
      temporal resolutions. We derive analytical predictions for the minimal time
      required to obtain a reliable image at a given spatial resolution. We find that
      the image completion time scales logarithmically with the ratio of the image size
      to the spatial resolution volume, with second order corrections due to spurious
      localization within the background noise. We validate our predictions against
      experimental localization sequences of labeled microtubule filaments obtained by
      STORM. Our theoretical framework makes it possible to compare the efficiency of
      emitters, define optimal labeling strategies, and allow implementation of a
      stopping criterion for data acquisitions that can be performed using real-time
      monitoring algorithms.

PMID- 29041619
TI  - Near-field thermal upconversion and energy transfer through a Kerr medium.
AB  - We present an approach for achieving large Kerr chi(3)-mediated thermal energy
      transfer at the nanoscale that exploits a general coupled-mode description of
      triply resonant, four-wave mixing processes. We analyze the efficiency of thermal
      upconversion and energy transfer from mid- to near-infrared wavelengths in planar
      geometries involving two slabs supporting far-apart surface plasmon polaritons
      and separated by a nonlinear chi(3) medium that is irradiated by externally
      incident light. We study multiple geometric and material configurations and
      different classes of intervening mediums-either bulk or nanostructured lattices
      of nanoparticles embedded in nonlinear materials-designed to resonantly enhance
      the interaction of the incident light with thermal slab resonances. We find that
      even when the entire system is in thermodynamic equilibrium (at room temperature)
      and under typical drive intensities ~ W/MUm2, the resulting upconversion rates
      can approach and even exceed thermal flux rates achieved in typical symmetric and
      non-equilibrium configurations of vacuum-separated slabs. The proposed nonlinear
      scheme could potentially be exploited to achieve thermal cooling and
      refrigeration at the nanoscale, and to actively control heat transfer between
      materials with dramatically different resonant responses.

PMID- 29041620
TI  - Forward bias operation of silicon photonic Mach Zehnder modulators for RF
      applications.
AB  - In this paper, we demonstrate that forward bias (+0.9V) of a high-speed silicon
      (Si) optical Mach-Zehnder modulator (MZM) increases the radio-frequency (RF) link
      gain by 30 dB when compared to reverse bias operation (-8V). RF applications
      require tunable, narrowband electro-optic conversion with high gain to mitigate
      noise of the optical receiver and realize high RF spur-free dynamic range.
      Compared to reverse bias, the forward bias gain rolls off more rapidly but offers
      higher RF link gain improvement of more than 13.2 dB at 20 GHz. Furthermore,
      forward bias is shown to result in comparable spurious-free dynamic range (SFDR:
      104.5 dB.Hz2/3). We demonstrate through an analytical dc transfer curve the
      existence of simultaneous high gain and OIP3 and verify the theoretical results
      with measurement under forward bias at a bias point of around +0.9 V.

PMID- 29041621
TI  - Removal of ring artifacts in microtomography by characterization of scintillator
      variations.
AB  - Ring artifacts reduce image quality in tomography, and arise from faulty detector
      calibration. In microtomography, we have identified that ring artifacts can arise
      due to high-spatial frequency variations in the scintillator thickness. Such
      variations are normally removed by a flat-field correction. However, as the
      spectrum changes, e.g. due to beam hardening, the detector response varies non
      uniformly introducing ring artifacts that persist after flat-field correction. In
      this paper, we present a method to correct for ring artifacts from variations in
      scintillator thickness by using a simple method to characterize the local
      scintillator response. The method addresses the actual physical cause of the ring
      artifacts, in contrary to many other ring artifact removal methods which rely
      only on image post-processing. By applying the technique to an experimental
      phantom tomography, we show that ring artifacts are strongly reduced compared to
      only making a flat-field correction.

PMID- 29041622
TI  - 2.4 THz/s continuously linearly frequency-modulated Nd:YVO4 laser.
AB  - We demonstrate a linearly frequency-modulated laser from a laser diode (LD)
      pumped Nd:YVO4 laser. A fast frequency tuning of 2.40 THz/s with a tuning range
      of 6 GHz is achieved in LD pumped Nd:YVO4 1064 nm laser by using RbTiOPO4 (RTP)
      crystals as the frequency modulator. The continuous tuning range is more than 3
      times the longitudinal mode spacing of the resonator. The maximum output power of
      frequency-modulated laser reaches 160 mW at 1064 nm. Linewidth of the single
      frequency laser is measured to be 190 kHz by a delay self-heterodyne
      interferometer. A deviation lower than 60 MHz is obtained during linear
      modulation.

PMID- 29041623
TI  - Near-field thermal radiation of deep- subwavelength slits in the near infrared
      range.
AB  - We numerically investigate the thermal radiation of one-dimensional deep
      subwavelength slits in the near infrared range. Using numerical calculations of
      single-slit and multi-slit structures, we find that high-level radiation
      efficiency can be achieved for a wide spectrum when ultra-thin intermediate
      layers are used, and it is less affected by structure parameters. The underlying
      mechanisms involve Surface Plasmon Polaritons resonance and Fabry-Perot
      interference at each slit and the interaction between adjacent slits. This
      structure helps understand and improve the design of thermal radiation control
      devices.

PMID- 29041624
TI  - Attenuation of model hollow-core, anti-resonant fibres.
AB  - An analytic expression is obtained for the confinement loss of model anti
      resonant fibres consisting of concentric regions of air and glass. Hankel
      functions in the regions surrounding the air core are approximated by their
      asymptotic form; apart from this, results are correct to leading order in the
      small parameter 1/(k0rc), where rc is the core radius and k0 the free space
      wavenumber. The results extend and generalise previous solutions for propagation
      in a hollow glass tube and a thin-walled capillary. Comparison with exact
      numerical calculations shows that the analytic expression provides an accurate
      description of the loss, including its dependence on the mode, the core radius
      and the widths of the surrounding glass and air regions. The relevance of the
      results to the recent generation of hollow-core, anti-resonant photonic crystal
      fibres is discussed.

PMID- 29041625
TI  - Rigorous full-wave calculation of optical forces on dielectric and metallic
      microparticles immersed in a vector Airy beam.
AB  - Based on the generalized Lorenz-Mie theory and the Maxwell stress tensor approach
      we present the first rigorous full-wave solution of the optical forces acting on
      spherical microparticles immersed in a two-dimensional vector Airy beam beyond
      the paraxial approximation. The critical aspect lies in evaluating efficiently
      and accurately the partial wave expansion coefficients of the incident Airy beam,
      which are achieved by using the vector angular spectrum representation for a
      variety of polarizations. The optical field distributions are then simulated to
      show the self-accelerating and self-healing effects of the Airy beam. The
      dielectric and gold microparticles are shown to be trapped within the main lobe
      or the nearby side-lobes mostly by the transverse gradient optical force while
      driven forward along the parabolic trajectory of the Airy beam by the
      longitudinal scattering force. It is thus demonstrated theoretically that the
      vector Airy beam has the capability of precisely transporting both dielectric and
      metallic microparticles along the prespecified curved paths.

PMID- 29041626
TI  - Modelocking of a thin-disk laser with the frequency-doubling nonlinear-mirror
      technique.
AB  - We demonstrate a frequency-doubling nonlinear-mirror (NLM) modelocked thin-disk
      laser. This modelocking technique, composed of an intracavity second harmonic
      crystal in combination with a dichroic output coupler, offers robust operation
      decoupled from cavity stability (as in semiconductor saturable absorber mirror
      (SESAM) modelocking) combined with an ultrafast saturable loss and high
      modulation depth (as in Kerr-lens modelocking (KLM)). With our NLM diode-pumped
      Yb:YAG thin-disk laser we achieve 21 W of average power at 323-fs pulse duration,
      which is an order of magnitude shorter than the previously obtained duration with
      the same technique in bulk lasers. Using these first results, we present a
      theoretical model for the NLM technique, which accurately predicts its loss
      modulation properties and the shortest achievable pulse duration without relying
      on any fitting parameters. Based on this simulation, we expect that the NLM
      technique will enable thin-disk lasers with average power of more than 100 W,
      with potentially sub-200 fs pulses. This could potentially solve the pulse
      duration limitations with SESAM modelocked Yb:YAG thin-disk lasers without
      imposing strong cavity stability constraints such as in KLM.

PMID- 29041627
TI  - 71-Mbit/s ultraviolet-B LED communication link based on 8-QAM-OFDM modulation.
AB  - A demonstration of ultraviolet-B (UVB) communication link is implemented
      utilizing quadrature amplitude modulation (QAM) orthogonal frequency-division
      multiplexing (OFDM). The demonstration is based on a 294-nm UVB-light-emitting
      diode (UVB-LED) with a full-width at half-maximum (FWHM) of 9 nm and light output
      power of 190 MUW, at 7 V, with a special silica gel lens on top of it. A -3-dB
      bandwidth of 29 MHz was measured and a high-speed near-solar-blind communication
      link with a data rate of 71 Mbit/s was achieved using 8-QAM-OFDM at perfect
      alignment. 23.6 Mbit/s using 2-QAM-OFDM when the angle subtended by the pointing
      directions of the UVB-LED and photodetector (PD) is 12 degrees, thus establishing
      a diffuse-line-of-sight (LOS) link. The measured bit-error rate (BER) of 2.8 *10
      4 and 2.4 *10-4, respectively, are well below the forward error correction (FEC)
      criterion of 3.8 *10-3. The demonstrated high data-rate OFDM-based UVB
      communication link paves the way for realizing high-speed non-line-of-sight free
      space optical communications.

PMID- 29041628
TI  - 500 W level MOPA laser with switchable output modes based on active control.
AB  - We report a high power transverse-mode-switchable fiber laser in a master
      oscillator power amplifier (MOPA) configuration. The output modes of a few-mode
      fiber amplifier can be actively controlled by the input polarization state of the
      fundamental mode seed laser using SPGD algorithm. A fast, stable and safety mode
      switching between LP01 and LP11 modes is achieved in the amplifier at output
      power of 500 W level.

PMID- 29041629
TI  - Practical approximation of the oceanic refractive index spectrum.
AB  - Oceanic turbulence is described by the oceanic refractive-index spectrum (ORIS),
      which considers several important hydrodynamic parameters. Based on ORIS, many
      optical oceanic quantities can be calculated using numerical integration.
      However, it is difficult to calculate the analytical solutions. In this paper, an
      approximate oceanic temperature spectrum is obtained by multiplying the non
      Kolmogorov spectrum with a correction factor. By analogy with the obtained
      temperature spectrum, an approximate salinity spectrum and an approximate
      coupling spectrum are obtained. A linear summation of these three approximate
      spectra forms the approximate form of ORIS. The approximate form of ORIS we
      obtained helps calculate the analytical solutions of the relevant oceanic optical
      quantities.

PMID- 29041630
TI  - Unidirectional edge states in topological honeycomb-lattice membrane photonic
      crystals.
AB  - Photonic analogs of electronic systems with topologically non-trivial behavior
      such as unidirectional scatter-free propagation has tremendous potential for
      transforming photonic systems. Like in electronics topological behavior can be
      observed in photonics for systems either preserving time-reversal (TR) symmetry
      or explicitly breaking it. TR symmetry breaking requires magneto-optic photonics
      crystals (PC) or generation of synthetic gauge fields. For on-chip photonics that
      operate at optical frequencies both are quite challenging because of poor magneto
      optic response of materials or substantial nanofabrication challenges in
      generating synthetic gauge fields. A recent work by Ma, et al. [Phys. Rev.
      Lett.114, 223901 (2015)] based on preserving pseudo TR symmetry offers a
      promising design scheme for observing unidirectional edge states in a modified
      honeycomb photonic crystal (PC) lattice of circular rods that offers encouraging
      alternatives. Here we propose through bandstructure calculations the inverse
      system of modified honeycomb PC of circular holes in a dielectric membrane which
      is more attractive from fabrication standpoint for on-chip applications. We
      observe trivial and non-trivial bandgaps as well as unidirectional edge states of
      opposite helicity propagating in opposite directions at the interface of a
      trivial and non-trivial PC structures. Around 1550nm operating wavelength ~55nm
      of bandwidth is possible for practicable values of design parameters (lattice
      constant, hole radii, membrane thickness, scaling factor etc.) and robust to
      reasonable variations in those parameters.

PMID- 29041631
TI  - Highly improved, non-localized field enhancement enabled by hybrid plasmon of
      crescent resonator/graphene in infrared wavelength.
AB  - The development of surface enhanced infrared absorption has been constrained by
      the limited field enhancement and narrow-band resonance of commonly used metal
      resonators. In this theoretical work, the design of a crescent resonator (CR)
      combined with graphene-enabled plasmon tuning is proposed to settle the
      drawbacks. The CR is similar to a split ring resonator (SRR), but exhibits a much
      improved field enhancement. The influence of graphene on the field enhancement of
      the CR has been systematically investigated. Coupling from localized plasmon of
      CR to propagating plasmon of graphene has been observed, and the constructive
      interference of the plasmon wave has led to not only better enhancement inside
      the gap but also usable enhancements all over the graphene film, which go beyond
      the localized nature of metal plasmons.

PMID- 29041632
TI  - Wavelength- and OAM-tunable vortex laser with a reflective volume Bragg grating.
AB  - Vortex beams carrying orbital angular momentum (OAM) have been recently
      investigated intensely in optical communication systems, as using OAM mode
      multiplexing simultaneously with other conventional multiplexing techniques is
      the key to further expand data capacity. This article demonstrates a wavelength-
      and OAM-tunable vortex laser at 1.6 um in an Er:YAG system. For the first time to
      the best of our knowledge, a reflective volume Bragg grating (VBG) was
      theoretically and experimentally proved to be an effective OAM-preserving
      wavelength selector inside the laser cavity. A z-shaped laser cavity employing a
      VBG as a folding mirror was constructed for the direct generation of vortex
      beams, and we finally obtained wavelength-tunable beams of five OAM states (0, +/
      h, and +/- 2h) with a narrow bandwidth less than 0.04 nm. This laser supplies a
      new way for optical communication by combining the spatial degree of freedom for
      multiplexing information channels with the conventionally used wavelength domains
      in packable and robust resonant cavity.

PMID- 29041633
TI  - High dynamic range head mounted display based on dual-layer spatial modulation.
AB  - The human visual system can perceive a much wider range of contrast than the
      addressable dynamic range afforded by the state-of-art head mounted displays
      (HMD). Increasing the dynamic range of HMDs becomes critical especially for
      augmented reality applications where the dynamic range of outdoor scenes can be
      as large as 14 orders of magnitude. In this paper, we present the integrated work
      of the design, implementation, calibration, and image-rendering algorithm of a
      high dynamic range HMD system. By using a pair of LCoS microdisplays as the
      spatial light modulators, accompanied with the relay optics to optically overlay
      the modulation layers, we demonstrate the reconstruction of high dynamic range
      images with high accuracy.

PMID- 29041634
TI  - Large area nanoimprint enables ultra-precise x-ray diffraction gratings.
AB  - A process for fabrication of ultra-precise diffraction gratings for high
      resolution x-ray spectroscopy was developed. A grating pattern with constant or
      variable line spacing (VLS) is recorded on a quartz plate by use of e-beam
      lithography with nanometer scale accuracy of the groove placement. The pattern is
      transferred to a massive grating blank by large area nanoimprint followed by dry
      or/and wet etching for groove shaping. High fidelity of the nanoimprint transfer
      step was confirmed by differential wavefront measurements. Successful
      implementation of the suggested fabrication approach was demonstrated by
      fabrication of a lamellar 900 lines/mm VLS grating for a soft x-ray fluorescence
      spectrometer.

PMID- 29041635
TI  - Ultra-thin infrared metamaterial detector for multicolor imaging applications.
AB  - The next generation of infrared imaging systems requires control of fundamental
      electromagnetic processes - absorption, polarization, spectral bandwidth - at the
      pixel level to acquire desirable information about the environment with low
      system latency. Metamaterial absorbers have sparked interest in the infrared
      imaging community for their ability to enhance absorption of incoming radiation
      with color, polarization and/or phase information. However, most metamaterial
      based sensors fail to focus incoming radiation into the active region of a ultra
      thin detecting element, thus achieving poor detection metrics. Here our
      multifunctional metamaterial absorber is directly integrated with a novel mid
      wave infrared (MWIR) and long-wave infrared (LWIR) detector with an ultra-thin
      (~lambda/15) InAs/GaSb Type-II superlattice (T2SL) interband cascade detector.
      The deep sub-wavelength metamaterial detector architecture proposed and
      demonstrated here, thus significantly improves the detection quantum efficiency
      (QE) and absorption of incoming radiation in a regime typically dominated by
      Fabry-Perot etalons. Our work evinces the ability of multifunctional
      metamaterials to realize efficient wavelength selective detection across the
      infrared spectrum for enhanced multispectral infrared imaging applications.

PMID- 29041636
TI  - True thermal antenna with hyperbolic metamaterials.
AB  - A thermal antenna is an electromagnetic source that emits in its surrounding a
      spatially coherent field in the infrared frequency range. Usually, its emission
      pattern changes with the wavelength so that the heat flux it radiates is weakly
      directive. Here, we show that a class of hyperbolic materials of type II possess
      a Brewster angle, which is weakly dependent on the wavelength, so that they can
      radiate like a true thermal antenna with a highly directional and p-polarized
      heat flux. The realization of these sources could open a new avenue in the field
      of thermal management in far-field regime.

PMID- 29041637
TI  - Optical angular momentum derivation and evolution from vector field
      superposition.
AB  - Optical intrinsic angular momentum can be regarded as derivation from spatial
      superposition of optical vector fields embodied by spinning or/and spiraling the
      electric-field vector. We employ vectorial formulation derivation to
      comprehensively study all angular momentum contents of optical vector fields in
      arbitrary superposition states, including the longitudinal and transverse, spin
      and orbital (SAM and OAM) components. As for the orthogonal superposition fields,
      there inherently exists spin-orbit shift from longitudinal SAM to OAM, and the
      whole local spin flow manifests local multiple-fold helical trajectories.
      Especially, both the spin-orbit shift and transverse SAM could become
      considerable in the non-paraxial condition. Our studies here provide an explicit
      insight into the derivation and evolution, intrinsic correlations and salient
      features of various types of angular momentum components.

PMID- 29041638
TI  - Minimization of 1/fn phase noise in liquid crystal masks for reliable femtosecond
      pulse shaping.
AB  - Liquid-crystal spatial light modulators (LCM) are a common tool to tailor
      femtosecond laser pulses. The phase stability of 1 kHz, sub-20 fs visible shaped
      and unshaped pulses are investigated. Our results show that the spectral phase
      after the LCM varies from pulse to pulse leading to strong deviations from the
      predicted pulse shapes. This phase instability is generated only by LCM and is
      strongly temperature dependent. Based on the experimental data, a numerical model
      for the phase was developed that takes the temperature-dependent phase
      instability as well as pixel coupling across the LCM into account. Phase
      stability after the LCM can be improved by an order of magnitude by combining the
      control the temperature of the LCM and by using rapid-scan averaging. Reliable
      pulse shapes on a pulse-to-pulse basis are crucial, especially in coherent
      control experiments, where small differences between pulse shape are important.

PMID- 29041639
TI  - Fluid jet-array parallel machining of optical microstructure array surfaces:
      publisher's note.
AB  - This publisher's note amends the funding section of [Opt. Express 25, 22710
      (2017)].

PMID- 29041640
TI  - Fiber optic mechanical deformation sensors employing perpendicular photonic
      crystals.
AB  - Existing fiber optics (FOs)-based sensors, including mechanical deformation ones
      rely on structures embedded along the length of the FO. In this paper, we
      introduce and evaluate photonic crystals (PCs) embedded into FO cores acting as
      mechanical deformation sensors which are departing from this classical approach
      as the PCs are perpendicular to the length of the FO. Another noteworthy
      difference from classical FO-PC based sensors is that while classical ones rely
      on amplitude variations, the ones presented here use the phase variations of the
      electromagnetic components for assessing mechanical deformations. We start with a
      straightforward rectangular-lattice PC while also exploring a triangular-lattice
      PC. Light transmission simulations through the proposed FO-PC mechanical
      deformation sensors were performed using EM Explorer, and revealed their
      behaviors under small mechanical deformations. These simulations (of the
      rectangular-lattice and triangular-lattice PCs) show that these two FO-PC
      mechanical deformation sensors have roughly the same sensitivities while the
      triangular-lattice PC triggers at a lower threshold than the rectangular-lattice
      PC.

PMID- 29041641
TI  - All-reflective multiphoton microscope.
AB  - We present the design, construction, and characterization of a multiphoton
      microscope that uses reflective elements for beam shaping and steering. This
      compact all reflective design removes the adverse effects of dispersion on laser
      pulse broadening as well as chromatic aberration in the focusing of broadband and
      multicolored laser sources. The design of this system is discussed in detail,
      including aberrations analysis via ray-tracing simulation and opto-mechanical
      design. The resolution of this mirror based all-reflective microscope is
      characterized using fluorescent microbeads. The performance of the system at
      multiple wavelengths is investigated along with some potential multiphoton
      imaging and writing applications.

PMID- 29041642
TI  - Weak-light vector rogue waves, breathers, and their Stern-Gerlach deflection via
      electromagnetically induced transparency.
AB  - We propose a scheme for generating and manipulating vector (or two-component)
      optical rogue waves using Akhmediev and Kuznetsov-Ma breathers in a coherent
      atomic system with an M-type five-level configuration via electromagnetically
      induced transparency (EIT). We show that the propagation velocity of these
      nonlinear excitations can be reduced to 10-4c and their generation power can be
      lowered to microwatts. We also show that the motion trajectories of the two
      polarization components in these excitations can be deflected significantly by
      using a transversal gradient magnetic field, similar to the Stern-Gerlach effect
      of an atomic beam. We find that the deflection angle can reach to 10-4 radian
      within the propagation distance of only several centimeters; at variance with the
      atomic Stern-Gerlach effect, the deflection angle can be made different for
      different polarization components and may be actively adjusted in a controllable
      way. The results obtained may have promising applications, including the precise
      measurement of gradient magnetic fields.

PMID- 29041644
TI  - Thermally induced mode loss evolution in the coiled ytterbium doped large mode
      area fiber.
AB  - We propose a model to calculate the thermally induced mode loss evolution in the
      coiled ytterbium doped large mode area (LMA) fiber. The mode loss evolution in
      the coiled conventional step index LMA 20/400 fiber is investigated. Meanwhile, a
      model of fiber amplifier considering thermally induced mode loss evolution is
      established. The higher order mode (HOM) suppression between a co-pumping scheme
      and counter-pumping scheme under the heat load are compared. The simulation shows
      that the HOM loss decreases quasi-exponentially with the heat load and the
      bending radius of the ytterbium doped fiber (YDF) should be optimized according
      to the heat load to achieve effectively single mode operation. Besides, the
      counter-pumping fiber amplifier shows much better HOM suppression than the co
      pumping fiber amplifier. The results in this paper will provide guidance in the
      design of novel ytterbium doped LMA fiber and the optimization of the high power
      single mode fiber amplifier.

PMID- 29041643
TI  - Spiral scanning X-ray fluorescence computed tomography.
AB  - Scanning X-ray fluorescence tomography was once considered impractical due to
      prohibitive measurement time requirements but is now common for investigating
      metal distributions within small systems. A recent look-ahead to the
      possibilities of 4th-generation synchrotron light sources [J. Synchrotron.
      Radiat. 21, 1031 (2014)] raised the possibility of a spiral-scanning measurement
      scheme where motion overheads are almost completely eliminated. Here we
      demonstrate the spiral scanning measurement and use Fourier ring correlation
      analysis to interrogate sources of resolution degradation. We develop an
      extension to the Fourier ring correlation formalism that enables direct
      determination of resolution from the measured sinogram data, greatly enhancing
      its power as a diagnostic tool for computed tomography.

PMID- 29041645
TI  - Single-shot 3D motion picture camera with a dense point cloud.
AB  - We discuss physical and information theoretical limits of optical 3D metrology.
      Based on these principal considerations we introduce a novel single-shot 3D movie
      camera that almost reaches these limits. The camera is designed for the 3D
      acquisition of macroscopic live scenes. Like a hologram, each movie-frame
      encompasses the full 3D information about the object surface and the observation
      perspective can be varied while watching the 3D movie. The camera combines single
      shot ability with a point cloud density close to the theoretical limit. No space
      bandwidth is wasted by pattern codification. With 1-megapixel sensors, the 3D
      camera delivers nearly 300,000 independent 3D points within each frame. The 3D
      data display a lateral resolution and a depth precision only limited by physics.
      The approach is based on multi-line triangulation. The requisite low-cost
      technology is simple. Only two properly positioned synchronized cameras solve the
      profound ambiguity problem omnipresent in 3D metrology.

PMID- 29041646
TI  - Designing freeform TIR optical elements using supporting quadric method.
AB  - The supporting quadric method (SQM) is a versatile method for the design of a
      wide class of freeform optical elements. In the present work, a novel SQM-based
      approach for the computation of total internal reflection (TIR) optical elements
      generating arbitrary narrow-angle light distributions is proposed. High
      performance of the presented method is confirmed by two designed optical
      elements: the first one forms an illuminance distribution in a square region with
      angular size of 17 degrees , and the second one generates a bat-shaped uniformly
      illuminated area with an angular size of 43.6 degrees  x 22.6 degrees . The
      lighting efficiencies in both cases exceed 90%, and the relative root-mean-square
      deviations of the generated light distributions from the required ones are less
      than 6%.

PMID- 29041648
TI  - Numerical investigation of nonlinear sound propagation of photoacoustic
      tomography imaging.
AB  - Almost all reconstruction methods in photoacoustic tomography (PAT) have been
      developed by assuming that sound propagation is linear, which is valid for
      ordinary PAT applications but would become inappropriate when the sound amplitude
      is higher than a certain threshold level. In the current study, we investigate
      the effect of nonlinear sound propagation on PAT by using a numerical method
      which utilizes the time-reversal (TR) technique. In the forward stage, the Euler
      equations are solved to simulate nonlinear sound propagation, and the flow
      variables (pressure, velocity and density) are recorded by an array of virtual
      sensors. The recorded data are used to reconstruct the initial fields within the
      computational domain by using both linear and nonlinear TR techniques.
      Furthermore, TR results constructed with and without the recorded flow velocity
      field, which is difficult to measure for practical applications, have also been
      compared. The current results show that nonlinear reconstructions produce images
      with superior clarity, resolution and contrast compared to those reconstructed by
      the linear method, particularly when the recorded velocity field is used in the
      reconstruction.

PMID- 29041647
TI  - Distributed backscattering in production O-band Si nanophotonic waveguides.
AB  - Backscattering in integrated photonic waveguides can significantly impact the
      performance of optical systems. However, it has not been extensively studied in
      the literature and measurements on waveguides fabricated in production foundry
      processes are particularly lacking in view of their importance to technology.
      Here we experimentally measure and analyze distributed backscattering in various
      production O-band silicon photonic waveguides. We find the measured
      backscattering to scale from -18 to -36 dB/mm. Measured trends across waveguide
      geometry and polarization are consistent with stochastic defects on waveguide
      sidewalls being the dominant source of distributed backscattering in production
      Si waveguides. For production SiNx waveguides, both sidewall and cladding defects
      need to be considered to fit measured trends.

PMID- 29041649
TI  - Exploring tunneling time by instantaneous ionization rate in strong-field
      ionization.
AB  - A quantum approach is presented to investigate tunneling time by supervising the
      instantaneous ionization rate. We find that the ionization rate peak appearance
      lags behind the maximum of electric field intensity for a linearly polarized
      pulse. This time delay interval can be taken to characterize the tunneling time.
      In addition, if an atom with anisotropic electronic distribution is exposed to a
      circular polarized pulse, the tunneling time can also be measured and defined as
      the time difference between the instant of the largest ionization rate and the
      moment when the electric field points in the maximum of the bound electron
      density.

PMID- 29041650
TI  - High harmonic generation from axial chiral molecules.
AB  - Axial chiral molecules, whose stereogenic element is an axis rather than a chiral
      center, have attracted widespread interest due to their important application,
      such as asymmetric synthesis and chirality transfer. We investigate high harmonic
      generation from axial chiral molecules with bichromatic counterrotating
      circularly polarized laser fields. High harmonic generation from three typical
      molecules: (Sa)-3-chloropropa-1,2-dien-1-ol, propadiene, and (Ra)-2,3-pentadiene
      is simulated with time-dependent density-functional theory and strong field
      approximation. We found that harmonic spectra for 3D oriented axial chiral
      molecules exhibit obvious circular dichroism. However, the circular dichroism of
      High harmonic generation from an achiral molecule is much trivial. Moreover, the
      dichroism of high harmonic generation still exists when axial chiral molecules
      are 1D oriented,such as (Sa) -3-chloropropa-1,2-dien-1-ol. For a special form of
      axial chiral molecules with the formula abC=C=Cab (a, b are different
      substituents), like (Ra)-2,3-pentadiene, the dichroism discriminations disappear
      when the molecules are only in 1D orientation. The circular dichroism of high
      harmonic generation from axial chiral molecules is well explained by the
      trajectory analysis based on the semiclassical three-step mechanism.

PMID- 29041651
TI  - Full three-dimensional isotropic carpet cloak designed by quasi-conformal
      transformation optics.
AB  - A fully three-dimensional carpet cloak presenting invisibility in all viewing
      angles is theoretically demonstrated. The design is developed using
      transformation optics and three-dimensional quasi-conformal mapping.
      Parametrization strategy and numerical optimization of the coordinate
      transformation deploying a quasi-Newton method is applied. A discussion about the
      minimum achievable anisotropy in the 3D transformation optics is presented. The
      method allows to reduce the anisotropy in the cloak and an isotropic medium could
      be considered. Numerical simulations confirm the strategy employed enabling the
      design of an isotropic reflectionless broadband carpet cloak independently of the
      incident light direction and polarization.

PMID- 29041652
TI  - Method of single-step full parallax synthetic holographic stereogram printing
      based on effective perspective images' segmentation and mosaicking.
AB  - With the principle of ray-tracing and the reversibility of light propagation, a
      new method of single-step full parallax synthetic holographic stereogram printing
      based on effective perspective images' segmentation and mosaicking (EPISM) is
      proposed. The perspective images of the scene are first sampled by a virtual
      camera and the exposing images, which are called synthetic effective perspective
      images, are achieved using the algorithm of effective perspective images'
      segmentation and mosaicking according to the propagation law of light and the
      viewing frustum effect of human eyes. The hogels are exposed using the synthetic
      effective perspective images in sequence to form the whole holographic
      stereogram. The influence of modeling parameters on the reconstructed images are
      also analyzed, and experimental results have demonstrated that the full parallax
      holographic stereogram printing with the proposed method could provide good
      reconstructed images by single-step printing. Moreover, detailed experiments with
      different holographic element sizes, different scene reconstructed distances, and
      different imaging planes are also analyzed and implemented.

PMID- 29041653
TI  - Uniform emission, constant wavevector silicon grating surface emitter for beam
      steering with ultra-sharp instantaneous field-of-view.
AB  - We report on uniform emission intensity profile, uniform propagation constant
      silicon gratings for beam steering application with ultra-sharp instantaneous
      field-of-view (IFOV). To achieve uniform emission intensity across relatively
      long emission length, we designed a custom grating with varying Si3N4 width and
      duty cycle while maintaining a uniform propagation constant for relatively narrow
      divergence emission pattern. We designed and fabricated the custom Si3N4/Si
      grating with the varying Si3N4 width/duty cycle together with the reference
      Si3N4/Si grating with a constant 50:50 duty cycle. The custom grating
      demonstrated the beam steering angle value of 6.6 degrees  by sweeping wavelength
      between 1530 nm and 1575 nm with the emission length over 1 mm. The measured IFOV
      based on the 3-dB beamwidth values of the far field patterns for the TE
      polarization are 0.10 degrees  and 0.75 degrees  for the custom grating and for
      the reference grating, respectively. The custom grating also indicates mode
      selective behavior due to the perturbation of propagation constant for input
      modes other than TE polarization. The measured TE-mode to TM-mode suppression
      ratio for the custom grating is approximately 8.2 dB peak-to-peak measured at far
      field.

PMID- 29041654
TI  - Tight focusing of laser light using a chromium Fresnel zone plate.
AB  - Using near-field scanning microscopy, we demonstrate that a 15-um zone plate
      fabricated in a 70-nm chromium film sputtered on a glass substrate and having a
      focal length and outermost zone's width equal to the incident wavelength lambda =
      532 nm, focuses a circularly polarized Gaussian beam into a circular
      subwavelength focal spot whose diameter at the full-width of half-maximum
      intensity is FWHM = 0.47lambda. This value is in near-accurate agreement with the
      FDTD-aided numerical estimate of FWHM = 0.46lambda. When focusing a Gaussian beam
      linearly polarized along the y-axis, an elliptic subwavelength focal spot is
      experimentally found to measure FWHMx = 0.42lambda (estimated value FWHMx =
      0.40lambda) and FWHMy = 0.64lambda. The subwavelength focal spots presented here
      are the tightest among all attained so far for homogeneously polarized beams by
      use of non-immersion amplitude zone plates.

PMID- 29041655
TI  - Single mode fiber based delivery of OAM light by 3D direct laser writing.
AB  - We demonstrate orbital-angular momentum (OAM) light up to a topological charge of
      l=3 behind a single mode fiber. Femtosecond 3D direct laser writing is used to
      fabricate spiral phase plates of l=1,2 and 3, composed of 10 discrete steps, on
      the tip of single mode optical fibers. These structures efficiently convert out
      coupled light from the fiber at 785 nm wavelength into optical vortex beams
      carrying an orbital-angular momentum of lhper photon. Far field intensity
      patterns and interferograms of the OAM beams are recorded using a CCD camera. The
      results are in excellent agreement with numerical simulations obtained from the
      wave propagation method.

PMID- 29041656
TI  - Multimode fiber modal decomposition based on hybrid genetic global optimization
      algorithm.
AB  - Numerical modal decomposition (MD) is an effective approach to reveal modal
      characteristics in high power fiber lasers. The main challenge is to find a
      suitable multi-dimensional optimization algorithm to reveal exact superposition
      of eigenmodes, especially for multimode fiber. A novel hybrid genetic global
      optimization algorithm, named GA-SPGD, which combines the advantages of genetic
      algorithm (GA) and stochastic parallel gradient descent (SPGD) algorithm, is
      firstly proposed to reduce local minima possibilities caused by sensitivity to
      initial values. Firstly, GA is applied to search the rough global optimization
      position based on near- and far-field intensity distribution with high accuracy.
      Upon those initial values, SPGD algorithm is afterwards used to find the exact
      optimization values based on near-field intensity distribution with fast
      convergence speed. Numerical simulations validate the feasibility and
      reliability.

PMID- 29041657
TI  - Formation, element-migration and broadband luminescence in quantum dot-doped
      glass fibers.
AB  - All solid-state PbS quantum dot (QD)-doped glass precursor fibers avoiding
      crystallization during fiber-drawing process are successfully fabricated by melt
      in-tube technique. By subsequent heat treatment schedule, controllable
      crystallization of PbS QDs can be obtained in the glass precursor fibers,
      contributing to broad near-infrared emissions from PbS QD-doped glass fibers.
      Nevertheless, we find that element-migration and volatilization of sulfur
      simultaneously happen during the whole fiber-drawing process, because of the huge
      difference between the melting temperature of core glass and the fiber-drawing
      temperature. Element-migration pathways along the fiber length were revealed.
      Such PbS QD-doped glass fiber with broadband emissions will be a potential
      application as gain medium of broadband fiber amplifiers and fiber lasers.

PMID- 29041658
TI  - Endoscopic imaging of quantum gases through a fiber bundle.
AB  - We use a coherent fiber bundle to demonstrate the endoscopic absorption imaging
      of quantum gases. We show that the fiber bundle introduces spurious noise in the
      picture mainly due to the strong core-to-core coupling. By direct comparison with
      free-space pictures, we observe that there is a maximum column density that can
      be reliably measured using our fiber bundle, and we derive a simple criterion to
      estimate it. We demonstrate that taking care of not exceeding such maximum, we
      can retrieve exact quantitative information about the atomic system, making this
      technique appealing for systems requiring isolation form the environment.

PMID- 29041659
TI  - Silicon photonic filters with high rejection of both TE and TM modes for on-chip
      four wave mixing applications.
AB  - Wavelength selective filters represent one of the key elements for photonic
      integrated circuits (PIC) and many of their applications in linear and non-linear
      optics. In devices optimised for single polarisation operation, cross
      polarisation scattering can significantly limit the achievable filter rejection.
      An on-chip filter consisting of elements to filter both TE and TM polarisations
      is demonstrated, based on a cascaded ring resonator geometry, which exhibits a
      high total optical rejection of over 60 dB. Monolithic integration of a cascaded
      ring filter with a four-wave mixing micro-ring device is also experimentally
      demonstrated with a FWM efficiency of -22dB and pump filter extinction of 62dB.

PMID- 29041660
TI  - Ultra-compact polarization rotation in integrated silicon photonics using digital
      metamaterials.
AB  - Polarization controlling devices such as polarization splitters and rotators are
      critical elements in integrated-photonic circuits that function via polarization
      diversity schemes. Here, we present the design of an ultra-compact nanophotonic
      polarization rotator (NPR) that rotates the polarization state from TE to TM with
      a simulated extinction ratio of 23dB over a coupling length of 5um and an
      operating bandwidth of 40nm. This all-silicon device can be fabricated in a
      single lithography step and we have fabricated and characterized a preliminary
      device exhibiting 9dB extinction ratio. To emphasize the generality of our
      methodology, we also designed a NPR that can rotate the polarization state from
      TM to TE as well. A small device footprint is enabled by the evanescent coupling
      of guided modes enabled by computationally designed digital metamaterials.

PMID- 29041661
TI  - High-efficiency tunable circular asymmetric transmission using dielectric
      metasurface integrated with graphene sheet.
AB  - High-efficiency tunable asymmetric transmission (AT) based on simple-constructed
      metasurface is highly desired for next generation optical polarization devices.
      Here, we numerically investigate high-efficiency and frequency-tunable circular
      AT effect in mid-infrared region by combining simple-shape silicon array with a
      graphene sheet. The asymmetric parameter of the dielectric nanostrip structure
      reaches 0.92 at 12.68 THz and the width of tunable spectra (AT > 0.7) is 1100 nm,
      which represent a major advance compared with previously reported AT. The AT
      behavior originates from extrinsic chirality induced by oblique illumination, and
      the high AT efficiency results from the constructive and deconstructive
      interferences of selectively excited electric and magnetic resonances. In
      addition, the working waveband of AT is shifted by dynamically modulating
      graphene's Fermi energy, which offers a new degree of freedom to achieve
      multifunctions without refabricating structures. The proposed array system
      possessing the merits of high efficiency, simple inclusions and frequency
      tunability has significant potentials for practical applications in polarization
      devices such as polarization sensor, polarizer, etc.

PMID- 29041662
TI  - Self-pulsing in kilowatt level narrow-linewidth fiber amplifier with WNS phase
      modulation.
AB  - The self-pulsing phenomenon in kilowatt level narrow-linewidth fiber amplifiers
      with white noise source (WNS) phase-modulation is observed experimentally. It
      possesses the obvious threshold of the pump power and prevents the narrow
      linewidth fiber lasers from further power scaling. The experimental study shows
      that known explanations are not applicable here and indicates that occurrence of
      self-pulsing is closely related to Stimulated Brillouin Scattering (SBS) process.
      The theoretical discussion reveals that the spikes in the modulated spectrum are
      the critical factor that SBS threshold is lower than the theoretical estimation.
      The 1+1 dimensional SBS model analysis predicts that self-pulsing originates from
      forward second order Stokes pulses, which is in good qualitative agreement with
      the experimental data.

PMID- 29041663
TI  - kHz-order linewidth controllable 1550 nm single-frequency fiber laser for
      coherent optical communication.
AB  - A kHz-order linewidth controllable 1550 nm single-frequency fiber laser (SFFL) is
      demonstrated for the first time to our best knowledge. The control of the
      linewidth is realized by using a low-pass filtered white Gaussian noise (WGN)
      signal applied on a fiber stretcher in an optical feedback loop. Utilizing WGN
      signals with different signal amplitudes An and different cutoff frequencies fc,
      the linewidths are availably controlled in a wide range from 0.8 to 353 kHz. The
      obtained optical signal-to-noise ratio (OSNR) is more than 72.0 dB, and the
      relative intensity noise (RIN) at frequency greater than 40 MHz reaches -148.5
      dB/Hz which approaches the shot noise limit (-152.9 dB/Hz). This kHz-order
      linewidth controllable SFFL is meaningful and valuable, for optimizing the
      receiver sensitivity and bit error rate (BER) performance of the coherent optical
      communication system based on high-order quadrature amplitude modulation (QAM).

PMID- 29041664
TI  - Diode-pumped passively Q-switched self-frequency-doubled Nd:CNGS laser.
AB  - With Cr4+:YAG as a saturable absorber, a passively Q-switched self-frequency
      doubled (SFD) laser based on a trigonal Nd:Ca3NbGa3Si2O14 (Nd:CNGS) silicate
      crystal was demonstrated for the first time. The maximum average output power at
      532 nm was 16.2 mW, and the corresponding pulse repetition frequency, single
      pulse energy, pulse duration and peak power were 2.25 kHz, 7.2 MUJ, 13.7 ns, 0.53
      kW, respectively. We also present a rate-equation model of such a passively Q
      switched SFD laser showing a good agreement with the experiment. Nd:CNGS is a
      promising pulse SFD material for miniature all-solid-state visible light sources.

PMID- 29041665
TI  - Multi-transverse mode operation of alkali vapor lasers: modeling and comparison
      with experiments.
AB  - In high-power diode pumped alkali lasers with stable resonators the radius of the
      pump beam is usually larger than that of the fundamental laser mode and thus
      several high order transverse modes of the resonator can participate in the
      lasing. A simple optical model of multi-transverse mode operation of alkali vapor
      lasers is reported. The model is based on calculations of the pump and laser beam
      intensities in the gain medium, where the laser beam intensity is a linear
      combination of the azimuthally-symmetric Laguerre-Gaussian modes. It was applied
      to Ti:Sapphire and diode pumped cesium vapor lasers. The model predicts that for
      low pump power only the fundamental lasing mode oscillates. However, for higher
      pump powers several transverse modes participate in oscillation. The number and
      intensities of the oscillating modes as a function of the pump beam power and
      radius were found. The model predicts linear dependence of the laser power on the
      pump power, the values of the former being in agreement with the experimental
      results obtained for diode pumped cesium laser [Electron. Lett.44, 582 (2008)].
      The mode-matching efficiency for the multi-transverse mode lasing is ~0.8 - 0.85
      which means that in this case almost complete overlap of the laser and pump beams
      takes place. The laser beam quality factorM2increases with increasing pump power
      from 1 at the threshold power to 5-6 at maximum values of the pump power
      resulting in lower beam quality at high powers.

PMID- 29041666
TI  - Pr:RbPb2Cl5: temperature dependent spectra, dynamics and three-for-one
      excitation.
AB  - The temperature dependence of the absorption, fluorescence, and fluorescence
      lifetimes of states relevant to short-wave-infrared and mid-infrared laser
      operation have been measured in Pr:RbPb2Cl5. The 3600-5500-nm fluorescence grows
      strongly with temperature, and at room temperature represents the large majority
      of the observed photon flux. Intra-ionic decay processes cannot explain this
      dominance, but a combination of two cross-relaxation processes provides good
      agreement with the data. These results indicate a three-for-one process: the
      excitation of nearly three ions to the 3H5 manifold of Pr3+ by each one initially
      excited to 3F3, with the potential for exceptionally high efficiency excitation
      of mid-infrared laser materials.

PMID- 29041667
TI  - Towards quantum communications in free-space seawater.
AB  - Long-distance quantum channels capable of transferring quantum states faithfully
      for unconditionally secure quantum communication have been so far confirmed to be
      feasible in both fiber and free-space air. However, it remains unclear whether
      seawater, which covers more than 70% of the earth, can also be utilized, leaving
      global quantum communication incomplete. Here we experimentally demonstrate that
      polarization quantum states including general qubits of single photon and
      entangled states can survive well after travelling through seawater. We perform
      experiments with seawater collected over a range of 36 kilometers in the Yellow
      Sea. For single photons at 405 nm in a blue-green window, we obtain an average
      process fidelity above 98%. For entangled photons at 810nm, albeit very high
      loss, we observe the violation of Bell inequality with 33 standard deviations.
      Our results confirm the feasibility of a seawater quantum channel, representing
      the first step towards underwater quantum communication.

PMID- 29041668
TI  - Origins of Kerr phase and orientational phase in polymer-dispersed liquid
      crystals.
AB  - Polymer-dispersed liquid crystals (PDLCs) modulate the amplitude and optical
      phase of light. The optical phase modulation of PDLC can be dissected into two
      parts: Kerr phase and orientational phase according to the electro-optical (EO)
      response. We investigated the origins of the Kerr and orientational phases in
      PDLCs and their connection with the two-step EO response. The Kerr phase is
      attributed to LC orientation in the center of LC droplets. The orientational
      phase results from orientation of LC molecules near LC-polymer interfaces. Both
      phases can be adjusted by varying the droplet size. The two-step EO response in
      small droplets (<333 nm) is related to the Kerr and orientational phases, and
      possibly to rotation of point defects. A modified PDLC model considering the Kerr
      and orientational phases is proposed. Our findings suggest the possibility of
      versatile photonic devices using pure optical phase modulation.

PMID- 29041669
TI  - Numerical investigations on photonic nanojet mediated surface enhanced Raman
      scattering and fluorescence techniques.
AB  - Finite element method simulations have been carried out on the photonic nanojet
      (PNJ) mediated surface enhanced Raman scattering (SERS) technique for the first
      time, and this technique has been found to provide (i) better Raman scattering
      enhancement of single molecules and (ii) a long working distance between the
      microscopic objective lens and sample, as compared with the conventional SERS
      technique. A PNJ mediated surface enhanced fluorescence (SEF) technique has been
      proposed to enhance the fluorescence of single molecules using the combination of
      localized surface plasmons inside nanostructures and the PNJ of a dielectric
      microsphere (MS), and this technique is numerically proved to be efficient as
      compared with a conventional SEF technique. Moreover, the generation of a PNJ
      from single lollipop shaped microstructures and its applications in the above
      mentioned techniques have been reported.

PMID- 29041670
TI  - Generalized optical angular momentum sorter and its application to high
      dimensional quantum cryptography.
AB  - The orbital angular momentum (OAM) carried by optical beams is a useful quantity
      for encoding information. This form of encoding has been incorporated into
      various works ranging from telecommunications to quantum cryptography, most of
      which require methods that can rapidly process the OAM content of a beam. Among
      current state-of-the-art schemes that can readily acquire this information are so
      called OAM sorters, which consist of devices that spatially separate the OAM
      components of a beam. Such devices have found numerous applications in optical
      communications, a field that is in constant demand for additional degrees of
      freedom, such as polarization and wavelength, into which information can also be
      encoded. Here, we report the implementation of a device capable of sorting a beam
      based on its OAM and polarization content, which could be of use in works
      employing both of these degrees of freedom as information channels. After
      characterizing our fabricated device, we demonstrate how it can be used for
      quantum communications via a quantum key distribution protocol.

PMID- 29041671
TI  - Tailoring the plasmon-induced transparency resonances in terahertz metamaterials.
AB  - We experimentally demonstrate that a coupled metamaterial composed of sub
      wavelength split-ring-resonators (SRRs) and closed-ring-resonators (CRRs) can
      tailor the plasmon-induced-transparency (PIT) resonances when the external
      electric field is parallel to the gaps of SRRs. Rotating or moving SRRs in
      vertical direction plays a critical role in the EIT functionality, while an
      excellent robust performance can be acquired via moving SRRs in the horizontal
      direction. Based on the results, a polarization-independent and polarization
      dependent planar metamaterial are designed, fabricated and measured. In contrast
      to the spectral property of the polarization-independent medium, the polarization
      dependent one is featured by isolated PIT phenomena in the frequency-domain, with
      respect to the horizontal and vertical polarized incident beam. Transmission
      responses of the PIT metamaterial are characterized with terahertz time-domain
      spectroscopy, showing a good agreement with the rigorous numerical simulation
      results. The presented work delivers a unique way to excite and modulate the PIT
      response, toward developing polarization-independent and polarization-dependent
      slow-light building blocks, ultrasensitive sensors and narrow-band filters
      functioning in the THz regime.

PMID- 29041672
TI  - Compact fiber CPA system based on a CFBG stretcher and CVBG compressor with
      matched dispersion profile.
AB  - In this work, a compact fiber chirped pulse amplification system exploiting a
      tandem of a chirped fiber Bragg grating stretcher and a chirped volume Bragg
      grating compressor with matched chromatic dispersion is presented. Chirped pulses
      of 230 ps duration were amplified in a Yb-doped fiber amplifier and re-compressed
      to 208 fs duration with good fidelity. The compressed pulse duration was fine
      tuned by temperature gradient along the fiber Bragg grating stretcher.

PMID- 29041673
TI  - Broad tunable photonic microwave generation based on period-one dynamics of
      optical injection vertical-cavity surface-emitting lasers.
AB  - Photonic microwave generation based on period-one dynamics of an optically
      injected VCSEL has been study experimentally. The results have shown that the
      frequency of the generated microwave signal can be broadly tunable through the
      adjustment of the injection power and the frequency detuning. Strong optical
      injection power and higher frequency detuning are favorable for obtaining a high
      frequency microwave signal. These results are similar to those found in systems
      based on distributed feedback lasers and quantum dot lasers. The variation of the
      microwave power at the fundamental frequency and the second-harmonic distortion
      have also been characterized.

PMID- 29041674
TI  - Rb/Ba side-diffused ridge waveguides in KTP.
AB  - We report on characterization of ridge waveguides fabricated in KTP (KTiOPO4) by
      use of diamond-blade dicing and Rb/Ba ion exchange. The waveguides were prepared
      in substrates that have their z-axis in the surface plane, perpendicular to the
      waveguide direction. This hinders the RbBa ions from diffusion into the depth, as
      they are only mobile along the z-axis, and improves the waveguide's resistance
      against elevated temperature. Attenuation coefficients of 0.3 dB/cm (0.4 dB/cm)
      for TM (TE) polarization were measured at 1060 nm wavelength. Internal conversion
      efficiency of up to 3.3%/(W cm2) was determined for type-II SHG of 1064 nm.

PMID- 29041675
TI  - Secchi disk observation with spectral-selective glasses in blue and green waters.
AB  - Radiative transfer modeling of Secchi disk observations has historically been
      based on conjugated signals of eye response and radiance, where water's
      attenuation in the entire visible band is included in the attenuation when
      deciding the Secchi disk depth in water. Aas et al. [Ocean Sci.10(2), 177
      (2014)Remote Sens. Environ.169, 139 (2015)] hypothesized that it is actually the
      attenuation in water's transparent window that matters to the observation of a
      Secchi disk in water. To test this hypothesis, observations of Secchi disks in
      blue and green waters were conducted via naked eyes, blue-pass glasses, and green
      pass glasses. Measurement results indicate that for blue waters, the observed
      Secchi depths via naked eyes match the depths obtained with blue-pass glasses and
      much deeper than the depths with green-pass glasses, although the green-pass
      glasses match the highest response of human eyes. These observations
      experimentally support the hypothesis that our eye-brain system uses the contrast
      information in the transparent window to make a judgement decision regarding
      sighting a Secchi disk in water.

PMID- 29041676
TI  - Scattering of Poincare beams: polarization speckles.
AB  - Polarization speckle is a fine granular light pattern having spatially varying
      random polarization profile. We generate these speckle patterns by using the
      scattering of Poincare beams, a special class of vector vortex beams, through a
      ground glass plate. Here, the Poincare beams are generated using a polarization
      sensitive spatial light modulator displaying an on-axis hologram corresponding to
      an optical vortex phase profile. The different inhomogeneities of the rough
      surface experience different polarizations, which control the ability for
      scattered waves to interfere at the detection plane and causes a spatially
      varying polarization profile. We experimentally determined the spatial variation
      of local degree of polarization and orientation of the polarization ellipse for
      these speckle patterns from the Stokes analysis. We also determined the size of
      scalar speckles using the auto-correlation function of Stokes parameter S0 and
      the size of polarization speckles using the sum of auto-correlation functions of
      remaining three Stokes parameters. We found that the change in scalar speckle
      size with the index of the vector beam is very small and of the order of 1 pixel
      size of the camera but the size of polarization speckles decreases with the
      increase in index of the vector beam.

PMID- 29041677
TI  - Ultrashort and efficient adiabatic waveguide taper based on thin flat focusing
      lenses.
AB  - A new structure is reported, which realizes the flat focusing by introducing the
      silicon subwavelength slits into the waveguide. The subwavelength silicon-air
      slits, with variable widths to match the phase compensation, makes possible to
      focus a plane wave. The flat lens proposed here demonstrates relatively high
      power gain at the focal point or two focal points. By using such a design, we
      demonstrate a grating coupler with an ultrashort taper of 22.5-MUm to connect a
      10-MUm-wide input waveguide and a 0.5-MUm-wide output waveguide, achieving a
      transmission up to nearly 95.4% numerically in the communication band. The length
      of which is one-twentieth of that for the traditional taper. To our best
      knowledge, this work is the first demonstration of an ultrashort taper based on
      flat lens, which significantly improves the integration of the photonics
      integrated circuits, and indicates an effective solution for potential
      applications in compactly integrated micro/nano optical devices.

PMID- 29041678
TI  - Fourier transform imaging spectropolarimeter using ferroelectric liquid crystals
      and Wollaston interferometer.
AB  - A time-division Fourier transform imaging spectropolarimeter (FTISP) for
      acquiring spatial, spectral, and polarized information is presented. The FTISP
      employs two ferroelectric liquid crystals (FLCs) and a Wollaston interferometer.
      The fast axes of the FLCs are controlled to switch quickly without mechanical
      movement, enabling the polarization state analyzer (PSA) to modulate the full set
      of Stokes parameters rapidly. The interferometer combines a Wollaston prism with
      a retroreflector, enabling high interference modulation and facilitating optical
      alignment. The optimal design for the FLC-PSA and Wollaston interferometer, and
      the Fourier transform recovery for the polarized interferogram, are presented in
      detail. To verify the proposed FTISP, laboratory and outdoor experiments were
      conducted, and the experimental results demonstrate that the proposed FTISP
      offers much promise for spectropolarimetric measurement with the advantages of
      fast speed, high spectral resolution, and high signal-to-noise ratio.

PMID- 29041679
TI  - Discrete solitons in optical fiber systems with large pre-dispersion.
AB  - With the aid of a discrete nonlinear Schrodinger equation (NLSE), the nonlinear
      interaction among the periodically placed ultrashort pulses is analyzed. If the
      amplitudes of these pulses are chosen to be secant-hyperbolic, it is found that
      they propagate without exchanging energy and hence the envelope of the peak of
      the short pulses is termed the discrete soliton in analogy with its counterpart
      in the spatial domain. In addition, we develop the concept of discrete chirp
      transform (DChT) and its inverse, and show that the weights of the pulses can be
      extracted from the field envelope using the discrete chirp transform (DChT). The
      computational cost of evaluating the output of a linear dispersive fiber using
      DChT approach is nearly half of the conventional frequency domain approach based
      on fast Fourier transform (FFT). We found that an isolated pump sinc pulse is not
      stable and it generates temporally separated sinc pulses if the dispersion of the
      transmission fiber is anomalous. By choosing a proper time separation between
      signal pulse and pump pulse, it is possible to amplify the signal pulse. The
      nonlinear interaction between signal pulse and pump pulse generates an idler
      pulse that is a phase-conjugated copy of the signal pulse. Hence, this result
      could have potential applications for time domain optical amplification and phase
      conjugation.

PMID- 29041680
TI  - Wavelength selective switch array employing silica-based waveguide frontend with
      integrated polarization diversity optics.
AB  - We propose a waveguide frontend with integrated polarization diversity optics for
      a wavelength selective switch (WSS) array with a liquid crystal on silicon
      switching engine to simplify the free space optics configuration and the
      alignment process in optical modules. The polarization diversity function is
      realized by the integration of a waveguide-type polarization beam splitter and a
      polarization rotating half-wave plate in a beam launcher using silica-based
      planar lightwave circuit technology. We confirmed experimentally the feasibility
      of using our proposed waveguide frontend in a two-in-one 1 * 20 WSS. The
      experimental results show that the fabricated waveguide frontend provides a
      polarization diversity function without any degradation in optical performance.

PMID- 29041681
TI  - Experimental and theoretical study of the in- fiber twist sensor based on quasi
      fan Solc structure filter.
AB  - In this paper, a novel quasi-fan Solc structure filter based on elliptical-core
      spun fiber for twist sensing has been experimentally investigated and
      theoretically analyzed. The discrete model of spun fiber has been built to
      analyze the transmission characteristics of proposed sensor. Both experimental
      and simulated results indicate that the extinction ratio of the comb spectrum
      based on quasi-fan Solc birefringent fiber filter varies with twist angle and
      agrees well with each other. Based on the intensity modulation, the proposed
      twist sensor exhibits a high sensitivity of 0.02219 dB/( degrees /m). Moreover,
      thanks to the invariability of the fiber birefringence and the state of
      polarization of the input light, the proposed twist sensor has a very low
      temperature and strain sensitivity, which can avoid the cross-sensitivity problem
      existing in most twist sensors.

PMID- 29041682
TI  - Focus issue introduction: recent advances in astrophotonics.
AB  - The first Optics Express Focus Issue on Astrophotonics was published in 2009.
      Since that time the field has experienced substantial growth and pathfinder
      astrophotonic systems are routinely being tested on large telescopes around the
      globe. This second Focus Issue on Astrophotonics is intended to capture some of
      these significant developments and convey a sense of future directions for the
      field.

PMID- 29041683
TI  - Measurement of direct strain optic coefficient of YSZ thermal barrier coatings at
      GHz frequencies.
AB  - We report the first observation of stress induced birefringence in air plasma
      sprayed (APS) thermal barrier coatings (TBCs) using a reflection based
      polariscope and GHz illumination. Strain optic coefficients of (-0.0133 +/-
      0.0102) * 10-9 and (-0.0190 +/- 0.0043) * 10-9 were measured for yttria
      stabilized zirconia (YSZ) APS coatings of the same thickness deposited on
      substrates of 3 mm and 1 mm mild steel. The reflection measurement approach was
      validated by additional measurements of the stress optic coefficient of bulk
      yttria-partially stabilized zirconia (YTZP) ceramic that were in agreement with
      previously reported transmission measurements. The ultimate application of this
      technique is the prediction of remaining life in TBCs.

PMID- 29041684
TI  - Thresholdless quantum dot nanolaser.
AB  - Thresholdless lasing is an outstanding challenge in laser science and is
      achievable only in devices having near unity quantum efficiency even when not
      lasing. Such lasers are expected to exhibit featureless linear light output
      curves. However, such thresholdless behavior hinders identification of the laser
      transition, triggering a long-lasting argument on how to identify the lasing.
      Here, we demonstrate thresholdless lasing in a semiconductor quantum dot
      nanolaser with a photonic crystal nanocavity. We employ cavity resonant
      excitation for enabling the thresholdless operation via focused carrier injection
      into high cavity field regions. Under conventional (above bandgap) excitation,
      the same nanolaser exhibits a typical thresholded lasing transition, thereby
      facilitating a systematic comparison between the thresholdless and thresholded
      laser transitions in the single device. Our approach enables a clear verification
      of the thresholdless lasing and reveals core elements for its realization using
      quantum dots, paving the way to the development of ultimately energy-efficient
      nanolasers.

PMID- 29041685
TI  - Performance analysis of an OAM multiplexing-based MIMO FSO system over
      atmospheric turbulence using space-time coding with channel estimation.
AB  - The average bit error rate (ABER) performance of an orbital angular momentum
      (OAM) multiplexing-based free-space optical (FSO) system with multiple-input
      multiple-output (MIMO) architecture has been investigated over atmospheric
      turbulence considering channel estimation and space-time coding. The impact of
      different types of space-time coding, modulation orders, turbulence strengths,
      receive antenna numbers on the transmission performance of this OAM-FSO system is
      also taken into account. On the basis of the proposed system model, the
      analytical expressions of the received signals carried by the k-th OAM mode of
      the n-th receive antenna for the vertical bell labs layered space-time (V-Blast)
      and space-time block codes (STBC) are derived, respectively. With the help of
      channel estimator carrying out with least square (LS) algorithm, the zero-forcing
      criterion with ordered successive interference cancellation criterion (ZF-OSIC)
      equalizer of V-Blast scheme and Alamouti decoder of STBC scheme are adopted to
      mitigate the performance degradation induced by the atmospheric turbulence. The
      results show that the ABERs obtained by channel estimation have excellent
      agreement with those of turbulence phase screen simulations. The ABERs of this
      OAM multiplexing-based MIMO system deteriorate with the increase of turbulence
      strengths. And both V-Blast and STBC schemes can significantly improve the system
      performance by mitigating the distortions of atmospheric turbulence as well as
      additive white Gaussian noise (AWGN). In addition, the ABER performances of both
      space-time coding schemes can be further enhanced by increasing the number of
      receive antennas for the diversity gain and STBC outperforms V-Blast in this
      system for data recovery. This work is beneficial to the OAM FSO system design.

PMID- 29041686
TI  - Development of precision elliptic neutron-focusing supermirror.
AB  - This paper details methods for the precision design and fabrication of neutron
      focusing supermirrors, based on electroless nickel plating. We fabricated an
      elliptic mirror for neutron reflectometry, which is our second mirror improved
      from the first. The mirror is a 550-millimeter-long segmented mirror assembled
      using kinematic couplings, with each segment figured by diamond cutting, polished
      using colloidal silica, and supermirror coated through ion-beam sputtering. The
      mirror was evaluated with neutron beams, and the reflectivity was found to be 68
      90% at a critical angle. The focusing width was 0.17 mm at the full width at half
      maximum.

PMID- 29041687
TI  - Passively mode-locked 1.34 MUm bulk laser based on few-layer black phosphorus
      saturable absorber.
AB  - By using few-layer black phosphorus (BP) as saturable absorber, an efficient mode
      locked Nd:GdVO4 bulk laser operating at 1.34 MUm was realized. An average output
      power of 350 mW was achieved with a slope efficiency of 15%. The corresponding
      mode-locking pulse repetition rate, pulse duration and pulse energy were 58.14
      MHz, 9.24 ps and 3.0 nJ, respectively. To the best of our knowledge, the pulse
      width is the shortest among the mode-locked 1.34 MUm neodymium lasers ever
      obtained with other two-dimensional materials saturable absorber. The results
      clearly indicate the few-layered BP is a kind of promising saturable absorber for
      ultrafast 1.34 MUm lasers.

PMID- 29041688
TI  - Simultaneous dual-color light sheet fluorescence imaging flow cytometry for high
      throughput marine phytoplankton analysis: retraction.
AB  - The referenced article [Opt. Express25, 13602 (2017)]10.1364/OE.25.013602 has
      been retracted.

PMID- 29041689
TI  - Fano enhancement in hybrid plasmonic nanoresonator.
AB  - Combining the advantages of photonics (low loss) and plasmonics (high field
      confinement), while mitigating their respective drawbacks, can greatly enhance
      the light-matter interaction efficiency. Here we make use of a time-dependent
      coupled mode theory in order to theoretically model the excitation of a plasmonic
      nanoantenna via a photonic resonator. We show that including the light source
      nanoantenna direct coupling substantially enhances the overall coupling
      efficiency, maintaining the same input power.

PMID- 29041690
TI  - Critical side channel effects in random bit generation with multiple
      semiconductor lasers in a polarization-based quantum key distribution system.
AB  - Most polarization-based BB84 quantum key distribution (QKD) systems utilize
      multiple lasers to generate one of four polarization quantum states randomly.
      However, random bit generation with multiple lasers can potentially open critical
      side channels that significantly endangers the security of QKD systems. In this
      paper, we show unnoticed side channels of temporal disparity and intensity
      fluctuation, which possibly exist in the operation of multiple semiconductor
      laser diodes. Experimental results show that the side channels can enormously
      degrade security performance of QKD systems. An important system issue for the
      improvement of quantum bit error rate (QBER) related with laser driving condition
      is further addressed with experimental results.

PMID- 29041691
TI  - Distributed optical fiber vibration sensor based on Sagnac interference in
      conjunction with OTDR.
AB  - A real-time distributed optical fiber vibration sensing prototype based on the
      Sagnac interference in conjunction with the optical time domain reflectometry
      (OTDR) was developed. The sensing mechanism for single- and multi-points
      vibrations along the sensing fiber was analyzed theoretically and demonstrated
      experimentally. The experimental results show excellent agreement with the
      theoretical models. It is verified that single-point vibration induces a
      significantly abrupt and monotonous power change in the corresponding position of
      OTDR trace. As to multi-points vibrations, the detection of the following
      vibration is influenced by all previous ones. However, if the distance between
      the adjacent two vibrations is larger than half of the input optical pulse width,
      abrupt power changes induced by them are separate and still monotonous. A time
      shifting differential module was developed and carried out to convert vibration
      induced power changes to pulses. Consequently, vibrations can be located
      accurately by measuring peak or valley positions of the vibration-induced pulses.
      It is demonstrated that when the width and peak power of input optical pulse are
      set to 1 MUs and 35 mW, respectively, the position error is less than +/- 0.5 m
      in a sensing range of more than 16 km, with the spatial resolution of ~110 m.

PMID- 29041692
TI  - Propagation of multi-cosine-Laguerre-Gaussian correlated Schell-model beams in
      free space and atmospheric turbulence.
AB  - We introduce a class of random stationary, scalar source named as multi-cosine
      Laguerre-Gaussian-correlated Schell-model (McLGCSM) source whose spectral degree
      of coherence (SDOC) is a combination of the Laguerre-Gaussian correlated Schell
      model (LGCSM) and multi-cosine-Gaussian correlated Schell-model (McGCSM) sources.
      The analytical expressions for the spectral density function and the propagation
      factor of a McLGCSM beam propagating in turbulent atmosphere are derived. The
      statistical properties, such as the spectral intensity and the propagation
      factor, of a McLGCSM beam are illustrated numerically. It is shown that a McLGCSM
      beam exhibits a robust ring-shaped beam array with adjustable number and
      positions in the far field by directly modulating the spatial structure of its
      SDOC in the source plane. Moreover, we provide a detailed insight into the
      theoretical origin and characteristics of such a ring-shaped beam array. It is
      demonstrated that these peculiar shaping properties are the concentrated
      manifestation of the individual merits respectively associated with the Laguerre-
      and multi-cosine-related factors of the whole SDOC. Our results provide a novel
      scheme to generate robust and controllable ring-shaped beam arrays over large
      distances, and will widen the potentials for manipulation of multiple particles,
      free-space optical communications and imaging in the atmosphere.

PMID- 29041693
TI  - Development of a fiber-optic gamma endoscope to measure both optical and gamma
      images in a confined space.
AB  - In nuclear medicine, obtaining information on the exact location, size, and dose
      of radiopharmaceuticals distributed on lesions is critically important.
      Therefore, we have fabricated a novel fiber-optic gamma endoscope (FOGE) to
      measure the shape and size of the radioisotope as well as the gamma-ray
      distribution simultaneously. To evaluate the performance of the novel FOGE, we
      obtained optical images and gamma images by using a USAF 1951 target and
      radioisotope sources, respectively. The experimental results demonstrated that
      the FOGE could be utilized to obtain both the location and the distribution of
      the radioactive isotope that emitted gamma-rays. Based on the results of this
      study, use of a flexible and thin FOGE would be valuable in nuclear medicine and
      nuclear safety technologies given the advantages of accurate dose-monitoring.
      Especially, improvements could be achieved in surgery technologies because the
      FOGE could be used in minimally invasive radioguided surgery owing to its thin
      form and flexibility.

PMID- 29041694
TI  - Non-diffractive Bessel-Gauss beams for the detection of rotating object free of
      obstructions.
AB  - Bessel-Gauss beams carrying orbital angular momentum are widely known for their
      non-diffractive or self-reconstructing performance, and have been applied in lots
      of domains. Here we demonstrate that, by illuminating a rotating object with high
      order Bessel-Gauss beams, a frequency shift proportional to the rotating speed
      and the topological charge is observed. Moreover, the frequency shift is still
      present once an obstacle exists in the path, in spite of the decreasing of
      received signals. Our work indicates the feasibility of detecting rotating
      objects free of obstructions, and has potential as obstruction-immune rotation
      sensors in engine monitoring, aerological sounding, and so on.

PMID- 29041695
TI  - Resolution enhancement in in-line holography by numerical compensation of
      vibrations.
AB  - Mechanical vibrations of components of the optical system is one of the sources
      of blurring of interference pattern in coherent imaging systems. The problem is
      especially important in holography where the resolution of the reconstructed
      objects depends on the effective size of the hologram, which is on the extent of
      the interference pattern, and on the contrast of the interference fringes. We
      discuss the mathematical relation between the vibrations, the hologram contrast
      and the reconstructed object. We show how vibrations can be post-filtered out
      from the hologram or from the reconstructed object assuming a Gaussian
      distribution of the vibrations. We also provide a numerical example of
      compensation for directional motion blur. We demonstrate our approach for light
      optical and electron holograms, acquired with both, plane- as well as spherical
      waves. As a result of such hologram deblurring, the resolution of the
      reconstructed objects is enhanced by almost a factor of 2. We believe that our
      approach opens up a new venue of post-experimental resolution enhancement in in
      line holography by adapting the rich database/catalogue of motion deblurring
      algorithms developed for photography and image restoration applications.

PMID- 29041696
TI  - Investigation of rectangular shaped wave packet dynamics in a high-repetition
      rate ultrafast fiber laser.
AB  - We identify a new regime where laser pulses represent the dynamics of rectangular
      shaped wave packets (RSWPs) in a passively mode-locked Tm3+-doped fiber laser. In
      this regime the laser consists of a train of mode-locked pulses underneath a
      rectangular-shaped envelope. The density of pulses within a RSWP can be as high
      as 2.8 GHz, which is consistent with cavity fundamental repetition rate. The
      effects of small-signal gain value, pulse repetition rate, and net dispersion on
      the RSWP performance are analyzed. These results imply that this new regime
      particularly favors high-repetition-rate ultrafast lasers. We further reproduce
      the phenomenon from using numerical simulations and understand such behavior by
      referring to the nonlinear dynamics.

PMID- 29041697
TI  - Focus-tunable double convex lens based on non-ionic electroactive gel.
AB  - We propose a focus-tunable double-convex (DCX) lens based on a non-ionic PVC
      (nPVC) gel to be used at close conjugates. The proposed lens is composed of an
      nPVC gel and two plates with electrodes. Each plate has a hole whose boundary and
      inner part are pasted with an electrode (anode) and has another ring shaped
      electrode (cathode) whose center point is the same as the hole's center. The gel
      is sandwiched between an upper plate and a lower plate, and it is bulged inward
      between the holes of two plates by applied pressure from the plates (double
      convex lens shape). The lens's focal length changed from 3 mm to 24.5 mm with
      applied voltages from 0 V to 400 V. We also observed that the proposed lens's
      field-of-view decreased from 121.9  degrees  to 41.9  degrees  according to the
      applied voltages. The proposed lens brings additional benefit for users with
      higher transmittance (over 94%).

PMID- 29041698
TI  - Real-time complex amplitude reconstruction method for beam quality M2 factor
      measurement.
AB  - We present a real-time complex amplitude reconstruction method for determining
      the beam propagation ratio M2 of laser beams based on the transport of intensity
      equation (TIE). In this work, a synchronous acquisition system consisting of two
      identical CCDs is established. Once two beam intensity images at different cross
      section positions along the optical axis are captured simultaneously by the
      system, the complex amplitude of the laser beam can be rapidly reconstructed
      using TIE algorithm. Then the beam intensity distribution at any section position
      along its propagation direction can be obtained by using angular spectrum (AS)
      theory. The beam quality M2 factor is therefore calculated utilizing the second
      order moments and hyperbola fitting methods, which conform to the ISO standard.
      The suitability of this method is verified by the numerical analysis and
      experiments with the He-Ne and high-power fiber laser sources, respectively. The
      experimental technique is simple and fast, which allows to investigate laser
      beams under conditions inaccessible to other methods.

PMID- 29041699
TI  - Photon heterodyning.
AB  - Single-photon interference experiments are attempted in the time domain using
      true single-photon streams. Self-heterodyning beats are clearly observed by
      letting the field associated with a single photon interfere with itself on a
      field-quadratic detector, which is a time analogue of Young's two-slit
      interference experiment. The temporal first-order coherence of single-photon
      fields, i.e., transient interference fringes, develops as cumulative detection
      events are mapped point-by-point onto a virtual capture frame by properly
      correlating the time-series data. The ability to single out photon counts at a
      designated timing paves the way for digital heterodyning with faint light for
      such use as phase measurement and quantum information processing.

PMID- 29041700
TI  - Synthetic aperture focusing technique for photoacoustic endoscopy.
AB  - Photoacoustic endoscopy (PAE) is a promising tool for the detection of
      atherosclerotic plaque. In this work, we propose a novel design of a side-viewing
      PAE probe based on a synthetic aperture focusing technique (SAFT) to enable high
      transverse resolution over large depth of focus (DOF) along the radial direction.
      A point-like ultrasonic detector is used to ensure a wide detection angle and
      thus a large synthetic aperture for SAFT. We first perform numerical simulation
      to optimize the PAE probe design, which involves the placement of the point-like
      detector and the diameter of a reflection rod mirror. Then, experiments are
      conducted based on the optimized probe design. High transverse resolution of 115
      190 um over large DOF of 3.5 mm along the radial direction is experimentally
      obtained. The SAFT-based PAE holds promise for endoscopic imaging with a high
      transverse resolution for both the surface and deep regions of tissue.

PMID- 29041701
TI  - Compact single-shot four-wavelength quantitative phase microscopy with
      polarization- and frequency-division demultiplexing.
AB  - We present a novel single-shot four-wavelength quantitative phase microscopy (FW
      QPM). Four lasers operating at different wavelengths are multiplexed with a pair
      of dichroic mirrors and a polarization beam splitter in a three-mirror quasi
      common-path interferometer. After a single-shot interference pattern is obtained
      with a monochrome camera, four holograms of different wavelengths were
      demultiplexed from it in the frequency domain with polarization- and frequency
      division multiplexing. Polarization-division demultiplexing scheme uses
      polarization dependent visibility changes in an interference pattern, and it
      plays a critical role in making only two interference patterns exist within a
      single quadrant in the frequency domain. We have used a single-mode optical fiber
      as a phase object sample and demonstrated that a measured single-shot
      interference pattern can be successfully demultiplexed into four different
      interferograms of different wavelengths with our proposed scheme.

PMID- 29041702
TI  - Towards large dynamic range and ultrahigh measurement resolution in distributed
      fiber sensing based on multicore fiber.
AB  - Featuring a dependence of Brillouin frequency shift (BFS) on temperature and
      strain changes over a wide range, Brillouin distributed optical fiber sensors are
      however essentially subjected to the relatively poor temperature/strain
      measurement resolution. On the other hand, phase-sensitive optical time-domain
      reflectometry (Phi-OTDR) offers ultrahigh temperature/strain measurement
      resolution, but the available frequency scanning range is normally narrow thereby
      severely restricts its measurement dynamic range. In order to achieve large
      dynamic range and high measurement resolution simultaneously, we propose to
      employ both the Brillouin optical time domain analysis (BOTDA) and Phi-OTDR
      through space-division multiplexed (SDM) configuration based on the multicore
      fiber (MCF), in which the two sensors are spatially separately implemented in the
      central core and a side core, respectively. As a proof of concept, the
      temperature sensing has been performed for validation with 2.5 m spatial
      resolution over 1.565 km MCF. Large temperature range (10  degrees C) has been
      measured by BOTDA and the 0.1  degrees C small temperature variation is
      successfully identified by Phi-OTDR with ~0.001  degrees C resolution. Moreover,
      the temperature changing process has been recorded by continuously performing the
      measurement of Phi-OTDR with 80 s frequency scanning period, showing about 0.02 
      degrees C temperature spacing at the monitored profile. The proposed system
      enables the capability to see finer and/or farther upon requirement in
      distributed optical fiber sensing.

PMID- 29041703
TI  - Tailored intensity landscapes by tight focusing of singular vector beams.
AB  - Vector beams are of major importance to tailor tightly focused fields by creating
      an additional z-polarization component. Till now, mainly focusing properties of
      fundamental vector beams have been investigated, whereas the knowledge of focused
      higher-order singular vector fields is still missing. We fill this gap by
      numerical analysis of these fields, applying their attractive characteristics as
      including a spatially adjustable amount of radial and azimuthal components. We
      demonstrate the realization of three-dimensional polarization structures whose
      total intensity resembles dark stars and bright flowers. Further, we tailor these
      focal intensity landscapes by modulating the order of incident vector fields.
      This in turn allows shaping the focus of a light field for specific applications
      as e.g. advanced microscopy.

PMID- 29041704
TI  - Optical and electrical trade-offs of rib-to-contact distance in depletion-type
      ring modulators.
AB  - We present a study on electrical and optical trade-offs of the doping map in a
      ring modulator. Here, we investigate the effects of the high-doped region
      distance to edge of the waveguide sidewall. Four groups of ring modulators with
      different rib-to-contact distances are fabricated and measured where the key
      parameters such as extinction ratio, insertion loss, transmission penalty, and
      bandwidth are compared quantitatively. Small-signal responses for the selected
      ring modulators are simulated where results are in agreement with measurement
      results. We show that, at 4dB extinction ratio, decreasing the high-doped region
      distance to rib from 800nm to 350nm will increase the bandwidth by 3.8 *.
      However, we observed 8.4dB increase the insertion loss. We also show that the
      high-doped region location affects the trade-off between bandwidth and frequency
      response magnitude at low frequencies. At 350nm, this trade off is 2.5 * and 3.8*
      more efficient compared to 550nm and 800nm, respectively.

PMID- 29041705
TI  - Depth-resolved local reflectance spectra measurements in full-field optical
      coherence tomography.
AB  - Full-field optical coherence tomography (FF-OCT) is a widely used technique for
      applications such as biological imaging, optical metrology, and materials
      characterization, providing structural and spectral information. By spectral
      analysis of the backscattered light, the technique of spectroscopic-OCT enables
      the differentiation of structures having different spectral properties, but not
      the determination of their reflectance spectrum. For surface measurements, this
      can be achieved by applying a Fourier transform to the interferometric signals
      and using an accurate calibration of the optical system. An extension of this
      method is reported for local spectroscopic characterization of transparent
      samples and in particular for the determination of depth-resolved reflectance
      spectra of buried interfaces. The correct functioning of the method is
      demonstrated by comparing the results with those obtained using a program based
      on electromagnetic matrix methods for stratified media. Experimental measurements
      of spatial resolutions are provided to demonstrate the smallest structures that
      can be characterized.

PMID- 29041706
TI  - Ultrafast optical pulse convertor caused by oscillations of the energy level
      structure in the conjugated polymer poly(p-phenylenevinylene).
AB  - For a conjugated polymer irradiated by two optical pulses, the whole process of
      excitation, involving lattice oscillations, oscillations of the energy level
      structure, and evolution of the electron cloud, is investigated. Localization of
      the electron cloud appears in the first 100 fs of irradiation, which in turn
      induces vibrations of lattice of the polymer chain as well as oscillations of the
      band gap. These oscillations filter the absorption of the external optical field
      inversely and convert the original optical field to an ultrafast light field
      whose intensity varies with a certain period. Based on the mechanism,
      oscillations of the energy level structure, induced by the external excitation,
      can be designed as an ultrafast response optical convertor that is able to change
      the external optical pulse into a new effective light field with a certain
      oscillation period. This helps provide new insight into designing nanostructures
      for polymeric optoelectronics.

PMID- 29041707
TI  - Translational, rotational, vibrational and electron temperatures of a gliding arc
      discharge.
AB  - Translational, rotational, vibrational and electron temperatures of a gliding arc
      discharge in atmospheric pressure air were experimentally investigated using in
      situ, non-intrusive optical diagnostic techniques. The gliding arc discharge was
      driven by a 35 kHz alternating current (AC) power source and operated in a glow
      type regime. The two-dimensional distribution of the translational temperature
      (Tt) of the gliding arc discharge was determined using planar laser-induced
      Rayleigh scattering. The rotational and vibrational temperatures were obtained by
      simulating the experimental spectra. The OH A-X (0, 0) band was used to simulate
      the rotational temperature (Tr) of the gliding arc discharge whereas the NO A-X
      (1, 0) and (0, 1) bands were used to determine its vibrational temperature (Tv).
      The instantaneous reduced electric field strength E/N was obtained by
      simultaneously measuring the instantaneous length of the plasma column, the
      discharge voltage and the translational temperature, from which the electron
      temperature (Te) of the gliding arc discharge was estimated. The uncertainties of
      the translational, rotational, vibrational and electron temperatures were
      analyzed. The relations of these four different temperatures (Te>Tv>Tr >Tt)
      suggest a high-degree non-equilibrium state of the gliding arc discharge.

PMID- 29041708
TI  - High-sensitivity photonic crystal fiber long-period grating methane sensor with
      cryptophane-A-6Me absorbed on a PAA-CNTs/PAH nanofilm.
AB  - A high-sensitivity photonic crystal fiber long-period grating (PCF-LPG) methane
      sensor with cryptophane-A-6Me absorbed on a poly(acrylic acid)-carbon nanotubes/
      polypropylene amine hydrochloride (PAA-CNTs/PAH) nanofilm was investigated. The
      sensing film was coated onto the internal surface of a photonic crystal fiber
      cladding air holes by an electrostatic self-assembly technique. Based on a finite
      element method and the coupled local-mode theory, the effects of the sensing
      film's refractive index (RI) and thickness on the resonant wavelength were
      theoretically and numerically analyzed. When the sensing film RI decreases from
      1.55 to 1.53, and the thickness increases from 100 nm to 200 nm, the resonant
      wavelength has a blue shift. A higher RI sensitivity with 1.075 * 103 nm RIU-1 is
      observed for the film thickness of 200 nm. The PCF-LPG methane sensor was
      fabricated by a pressurized injection method. The sensing experimental result
      shows that the resonant wavelength of the transmission spectra has a blue shift
      when the methane concentration increases from 0.0% to 3.5% by volume. The sensor
      has a good sensitivity of 1.078 nm%-1 and a low detection limit of 0.18% for a
      film thickness of 210 nm.

PMID- 29041709
TI  - Hybrid modes in plasmonic cavity array for enhanced hot-electron photodetection.
AB  - The plasmonic characteristics of a periodic array of cavities in a silicon
      substrate are investigated for hot-electron photodetection. Resonances of cavity
      surface plasmons bound to air cavities and silicon cavities, and resonance of
      Bragg-surface plasmon polaritons are illustrated by the map of metal absorption.
      Hybrid modes formed with combination of these modes can strongly enhance
      absorption in metal and be exploited to optimize hot-electron photodetectors for
      single-band and dual-band detection at optical communication wavelengths.

PMID- 29041710
TI  - Beam shaping with tip-tilt varifocal mirror for indoor optical wireless
      communication.
AB  - MEMS mirrors are currently used in many applications to steer beams of light. An
      area of continued research is developing mirrors with varifocal capability that
      allows the beam to be shaped and focused. In this work, we study the varifocal
      capability of a 380 MUm diameter, thermally actuated MEMS mirror with a +/- 40
      degrees  tip-tilt angle and a radius of curvature between -0.48 mm to 20.5 mm.
      Light is coupled to the mirror via a single mode optical fiber, similar to an
      indoor optical wireless communication architecture. The performance of the mirror
      is characterized with respect to (1) the profile of the reflected beam as the
      mirror deforms and (2) the mirror's impact when integrated into an optical
      communication system. We found that the mirror can focus light to a beam with a
      0.18 degrees  half-angle divergence. Additionally, the ability to change the
      shape of fiberized light from a wide to narrow beam provides an unmatched level
      of dynamic control and significantly improves the bit error rate in an optical
      communication system.

PMID- 29041711
TI  - High-order modulation on a single discrete eigenvalue for optical communications
      based on nonlinear Fourier transform.
AB  - In this paper, we experimentally investigate high-order modulation over a single
      discrete eigenvalue under the nonlinear Fourier transform (NFT) framework and
      exploit all degrees of freedom for encoding information. For a fixed eigenvalue,
      we compare different 4 bit/symbol modulation formats on the spectral amplitude
      and show that a 2-ring 16-APSK constellation achieves optimal performance. We
      then study joint spectral phase, spectral magnitude and eigenvalue modulation and
      found that while modulation on the real part of the eigenvalue induces pulse
      timing drift and leads to neighboring pulse interactions and nonlinear inter
      symbol interference (ISI), it is more bandwidth efficient than modulation on the
      imaginary part of the eigenvalue in practical settings. We propose a spectral
      amplitude scaling method to mitigate such nonlinear ISI and demonstrate a record
      4 GBaud 16-APSK on the spectral amplitude plus 2-bit eigenvalue modulation (total
      6 bit/symbol at 24 Gb/s) transmission over 1000 km.

PMID- 29041712
TI  - Use of Debye's series to determine the optimal edge-effect terms for computing
      the extinction efficiencies of spheroids.
AB  - The extinction efficiencies of atmospheric particles are essential to determining
      radiation attenuation and thus are fundamentally related to atmospheric radiative
      transfer. The extinction efficiencies can also be used to retrieve particle sizes
      or refractive indices through particle characterization techniques. This study
      first uses the Debye series to improve the accuracy of high-frequency extinction
      formulae for spheroids in the context of Complex angular momentum theory by
      determining an optimal number of edge-effect terms. We show that the optimal edge
      effect terms can be accurately obtained by comparing the results from the
      approximate formula with their counterparts computed from the invariant imbedding
      Debye series and T-matrix methods. An invariant imbedding T-matrix method is
      employed for particles with strong absorption, in which case the extinction
      efficiency is equivalent to two plus the edge-effect efficiency. For weakly
      absorptive or non-absorptive particles, the T-matrix results contain the
      interference between the diffraction and higher-order transmitted rays.
      Therefore, the Debye series was used to compute the edge-effect efficiency by
      separating the interference from the transmission on the extinction efficiency.
      We found that the optimal number strongly depends on the refractive index and is
      relatively insensitive to the particle geometry and size parameter. By building a
      table of optimal numbers of edge-effect terms, we developed an efficient and
      accurate extinction simulator that has been fully tested for randomly oriented
      spheroids with various aspect ratios and a wide range of refractive indices.

PMID- 29041713
TI  - Surface plasmon resonance biosensor based on gold-coated side-polished hexagonal
      structure photonic crystal fiber.
AB  - The refractive index sensing characteristics of the side-polished photonic
      crystal fiber (PCF) surface plasmon resonance (SPR) sensor are detailed
      investigated in this paper. We used the finite element method (FEM) to study the
      influences of the side-polished depth, air hole size, lattice constant, and the
      refractive index (RI) of the PCF material on sensing performance. The simulation
      results show that the side-polished depth, air hole size, lattice pitch have
      significant influence on the coupling strength between core mode and surface
      plasmon polaritons (SPPs), but have little influence on sensitivity; the coupling
      strength and sensitivity will significant increase with the decrease of RI of the
      PCF material. The sensitivity of the D-shaped PCF sensor is obtained to be as
      high as 21700 nm/RIU in the refractive index environment of 1.33-1.34, when the
      RI of the PCF material is controlled at 1.36. It revealed a new method of making
      ultra-high sensitivity SPR fiber sensor. Then we experimental demonstrated a SPR
      refractive sensor based on the side-polished single mode PCF and investigated the
      sensing performance. The experimental results of the plasmon resonance wavelength
      sensitivity agree well with the theoretical results. The presented gold-coated D
      shaped PCF SPR sensor could be used as a simple, cost-effective, high sensitivity
      device in bio-chemical detection.

PMID- 29041714
TI  - Real-time in situ study of femtosecond-laser-induced periodic structures on
      metals by linear and nonlinear optics.
AB  - Femtosecond-laser surface structuring on metals is investigated in real time by
      both fundamental and second harmonic generation (SHG) signals. The onset of
      surface modification and its progress can be monitored by both the fundamental
      and SHG probes. However, the dynamics of femtosecond-laser-induced periodic
      surface structures (FLIPSSs) formation can only be revealed by SHG but not
      fundamental because of the higher sensitivity of SHG to structural geometry on
      metal. Our technique provides a simple and effective way to monitor the surface
      modification and FLIPSS formation thresholds and allows us to obtain the optimal
      FLIPSS for SHG enhancement.

PMID- 29041715
TI  - Galilean monocentric multiscale optical systems.
AB  - The first generation of monocentric multiscale gigapixel cameras used Keplerian
      designs to enable full field coverage. This paper considers alternative designs
      that remove the requirement that adjacent subimages overlap. Removing this
      constraint enables Galilean designs that reduce system volume and improve
      relative illumination and image quality. The entrance aperture can also be moved
      to more closely approximate telecentricity and gaps in the field of view can be
      filled using multiple co-boresighted MMS cameras. Even with multiple cameras,
      Galilean systems can still reduce the total volume by 10 times relative to
      previous Keplerian designs.

PMID- 29041716
TI  - Efficient method to measure the spectral distortions using periodically
      distributed slit in hyperspectral imager.
AB  - The imaging spectrometer generally shows geometrical asymmetric distortions known
      as the keystone and smile that are different from the regular imaging optical
      system. The conventional method of measuring such distortions requires a
      precision movement control stage and specialized optical setup. Moreover, it is
      even harder to measure other characteristics such as the wave front error (WFE)
      simultaneously and to repeat the measurements since an accumulated vast number of
      statistical data is required to calculate the keystone and smile. To overcome
      these disadvantages, a new and simple method is proposed. The newly proposed
      method takes images separated in fields and wavelengths utilizing a simple tool
      called the field identifier (FI). Then, the keystone and the smile are calculated
      fast and repeatedly from a single measurement image while measuring the WFE with
      the Shack-Hartmann sensor with the minimum change of the measurement setup. With
      this method, hyperspectral imager is aligned and its geometrical distortions are
      measured.

PMID- 29041717
TI  - Simple autocorrelation method for thoroughly characterizing single-photon
      detectors.
AB  - We introduce and demonstrate a simple and highly sensitive method for
      characterizing single-photon detectors. This method is based on analyzing multi
      order correlations among time-tagged detection events from a device under
      calibrated continuous-wave illumination. First- and second-order properties such
      as detection efficiency, dark count rate, afterpulse probability, dead time, and
      reset behavior are measured with high accuracy from a single data set, as well as
      higher-order properties such as higher-order afterpulse effects. While the
      technique is applicable to any type of click/no-click detector, we apply it to
      two different single-photon avalanche diodes, and we find that it reveals a
      heretofore unreported afterpulse effect due to detection events that occur during
      the device reset.

PMID- 29041718
TI  - Tracking capacitance of liquid crystal devices to improve polarization rotation
      accuracy.
AB  - We report a capacitance tracking method for achieving arbitrary polarization
      rotation from nematic liquid crystals. By locking to the unique capacitance
      associated with the molecular orientation, any polarization rotation can be
      achieved with improved accuracy over a wide temperature range. A modified
      relaxation oscillator circuit that can simultaneously determine the capacitance
      and drive the rotator is presented.

PMID- 29041719
TI  - Asymmetric integral imaging system for a see-through three-dimensional display
      with background imaging function.
AB  - A see-through three-dimensional display with variable background imaging function
      is proposed. The proposed display system is based on integral imaging and
      consists of three lens arrays and a transparent flat-panel display. An asymmetric
      alignment of the three lens arrays enables variable background imaging. The
      background scene situated at any distance from the display system can be imaged
      at an intended distance from the display system. The possible imaging regions are
      shown. The proposed technique was experimentally verified using two optical
      systems that consisted of lens arrays with large and small lens pitches.

PMID- 29041720
TI  - Robust and efficient multi-frequency temporal phase unwrapping: optimal fringe
      frequency and pattern sequence selection.
AB  - Temporal phase unwrapping (TPU) is an essential algorithm in fringe projection
      profilometry (FPP), especially when measuring complex objects with
      discontinuities and isolated surfaces. Among others, the multi-frequency TPU has
      been proven to be the most reliable algorithm in the presence of noise. For a
      practical FPP system, in order to achieve an accurate, efficient, and reliable
      measurement, one needs to make wise choices about three key experimental
      parameters: the highest fringe frequency, the phase-shifting steps, and the
      fringe pattern sequence. However, there was very little research on how to
      optimize these parameters quantitatively, especially considering all three
      aspects from a theoretical and analytical perspective simultaneously. In this
      work, we propose a new scheme to determine simultaneously the optimal fringe
      frequency, phase-shifting steps and pattern sequence under multi-frequency TPU,
      robustly achieving high accuracy measurement by a minimum number of fringe
      frames. Firstly, noise models regarding phase-shifting algorithms as well as 3-D
      coordinates are established under a projector defocusing condition, which leads
      to the optimal highest fringe frequency for a FPP system. Then, a new concept
      termed frequency-to-frame ratio (FFR) that evaluates the magnitude of the
      contribution of each frame for TPU is defined, on which an optimal phase-shifting
      combination scheme is proposed. Finally, a judgment criterion is established,
      which can be used to judge whether the ratio between adjacent fringe frequencies
      is conducive to stably and efficiently unwrapping the phase. The proposed method
      provides a simple and effective theoretical framework to improve the accuracy,
      efficiency, and robustness of a practical FPP system in actual measurement
      conditions. The correctness of the derived models as well as the validity of the
      proposed schemes have been verified through extensive simulations and
      experiments. Based on a normal monocular 3-D FPP hardware system, our method
      enables high-precision unambiguous 3-D shape measurement with the highest fringe
      frequency up to 180 by using only 7 fringe patterns achieving a depth precision ~
      38MUm across a field of view of 400 * 300 * 400 mm.

PMID- 29041721
TI  - Quantitative calibration of sound pressure in ultrasonic standing waves using the
      Schlieren method.
AB  - We investigated the use of the Schlieren method to calibrate the sound pressure
      in an ultrasonic standing-wave field. Specifically, we derived an equation to
      calculate the light intensity of the diffraction fringe induced by the standing
      wave field. The results indicated that the sound pressure in the standing-wave
      field relates to the light intensity of the diffraction fringe. Simulations and
      experiments were conducted to verify the theoretical calculation. We demonstrated
      that the ratio of the light intensity of different diffraction orders relates to
      the sound pressure amplitude, allowing the pressure amplitude to be calibrated
      with the Schlieren method. Therefore, this work presents a non-intrusive
      calibration method that is particularly suitable for calibrating high-frequency
      ultrasonic standing-wave fields.

PMID- 29041722
TI  - High Verdet constants and diamagnetic responses of GeS2-In2S3-PbI2 chalcogenide
      glasses for integrated optics applications.
AB  - Chalcogenide glasses as kind of diamagnetic magneto-optical materials have
      promising applications in the field of integrated optics and optical
      communication systems due to their excellent properties, such as easy to be
      processed into waveguide and temperature independence of the Verdet constants.
      For clarifying the influence factors following the compositional variation on
      Faraday effect and finding a glass with a large Verdet constant, novel pseudo
      ternary chalcogenide glass system, GeS2 - In2S3 - PbI2, was prepared and
      investigated. The composition, wavelength and temperature dependences on the
      Verdet constants were systematically investigated at the wavelengths of 635, 808,
      980 and 1319 nm. PbI2 was confirmed to have positive contribution to the Verdet
      constant and the Becquerel rule was proved to be an effective guidance for
      predicting the Verdet constant in chalcogenide glasses. The 60GeS2.15In2S3.25PbI2
      glass was found to possess the largest Verdet constant (V = 0.215 min.G-1.cm-1,
      @808nm), which is great larger than that of commercial diamagnetic glasses. These
      glasses also possess good glass-forming ability and VIS-IR transmittance,
      therefore be a good candidate for next-generation integrated optical isolator and
      other magneto-optical devices.

PMID- 29041723
TI  - Broadband near-field infrared spectroscopy with a high temperature plasma light
      source.
AB  - Scattering-type scanning near-field optical microscopy (S-SNOM) has enormous
      potential as a spectroscopy tool in the infrared spectral range where it can
      probe phonon resonances and carrier dynamics at the nanometer lengths scales.
      However, its applicability is limited by the lack of practical and affordable
      table-top light sources emitting intense broadband infrared radiation in the 100
      cm-1 to 2,500 cm-1 spectral range. This paper introduces a high temperature
      plasma light source that is both ultra-broadband and has much more radiant power
      in the infrared spectral range than conventional, table-top thermal light sources
      such as the globar. We implement this plasma lamp in our near-field optical
      spectroscopy set up and demonstrate its capability as a broadband infrared nano
      spectroscopy light source by obtaining near-field infrared amplitude and phase
      spectra of the phonon resonances of SiO2 and SrTiO3.

PMID- 29041724
TI  - Ballistic imaging through an intense scattering medium using a supercontinuum
      with a roundabout spatial gate.
AB  - We propose a new ballistic imaging method that is capable of imaging an object
      through an intense scattering medium. In this method, a femtosecond
      supercontinuum and a roundabout spatial gate were used to suppress speckles and
      filter background noise, respectively. The roundabout spatial gate extracts
      ballistic light and avoids low-pass spatial filtering to ensure the high
      resolution of images. The experimental results showed that even when the optical
      depth of the scattering medium reached 17, the images extracted by the method had
      improved identifiability and contrast.

PMID- 29041725
TI  - Full stabilization and characterization of an optical frequency comb from a diode
      pumped solid-state laser with GHz repetition rate.
AB  - We demonstrate the first self-referenced full stabilization of a diode-pumped
      solid-state laser (DPSSL) frequency comb with a GHz repetition rate. The Yb:CALGO
      DPSSL delivers an average output power of up to 2.1 W with a typical pulse
      duration of 96 fs and a center wavelength of 1055 nm. A carrier-envelope offset
      (CEO) beat with a signal-to-noise ratio of 40 dB (in 10-kHz resolution bandwidth)
      is detected after supercontinuum generation and f-to-2f interferometry directly
      from the output of the oscillator, without any external amplification or pulse
      compression. The repetition rate is stabilized to a reference synthesizer with a
      residual integrated timing jitter of 249 fs [10 Hz - 1 MHz] and a relative
      frequency stability of 10-12/s. The CEO frequency is phase-locked to an external
      reference via pump current feedback using home-built modulation electronics. It
      achieves a loop bandwidth of ~150 kHz, which results in a tight CEO lock with a
      residual integrated phase noise of 680 mrad [1 Hz - 1 MHz]. We present a detailed
      characterization of the GHz frequency comb that combines a noise analysis of the
      repetition rate frep, of the CEO frequency fCEO, and of an optical comb line at
      1030 nm obtained from a virtual beat with a narrow-linewidth laser at 1557 nm
      using a transfer oscillator. An optical comb linewidth of about 800 kHz is
      assessed at 1-s observation time, for which the dominant noise sources of frep
      and fCEO are identified.

PMID- 29041726
TI  - Realizing structural color generation with aluminum plasmonic V-groove
      metasurfaces.
AB  - Structural color printing based on all-aluminum plasmonic V-groove metasurfaces
      is demonstrated under both bright field and dark field illumination conditions. A
      broad visible color range is realized with the plasmonic V-groove arrays etched
      on an aluminum surface by simply varying the groove depth while keeping the
      groove period as a constant. Polarization dependent structural color printing is
      further achieved with interlaced V-groove arrays along both the horizontal and
      vertical directions. These results pave the way towards the use of an all
      aluminum structural color printing platform for many practical applications such
      as security marking and information storage.

PMID- 29041727
TI  - Optimization of nano-honeycomb structures for flexible w-LEDs.
AB  - This study presents the low cost fabrication of flexible white-light-emitting
      diodes (w-LEDs) with nano-honeycomb-structured phosphor films. Extending the
      dimensions of the nano-honeycomb structures improved the color uniformity of the
      flexible samples, and the 950-nm pattern sample demonstrated optimal color
      uniformity because this nano-pattern exhibited an excellent diffusion ability
      owing to its pitch size. In addition to color uniformity, the use of this nano
      pattern improved the luminous efficiency. The 750-nm pattern exhibited the
      highest luminous efficiency (235.8 lm/W), which was approximately 7% higher than
      that exhibited by a non-patterned phosphor film sample. Thus, flexible w-LEDs
      with nano-honeycomb structure optimization have great potential to be used as
      next-generation lighting sources.

PMID- 29041728
TI  - Transition radiation from graphene plasmons by a bunch beam in the terahertz
      regime.
AB  - The terahertz band is an increasingly important spectrum in a wide range of
      applications from bioimaging and medical diagnostics to security and wireless
      communications. We propose a tunable terahertz coherent radiation source based on
      graphene plasmon-induced transition radiation. The transition radiation in
      terahertz regime arises from the graphene plasmons, which are excited by a
      normally incident bunched electron beam. We analyze the field-intensities and
      spectral-angular distributions of the transition radiation with respect to Fermi
      energy, substrate dielectric permittivity, and electron bunch energy for both the
      coherent and incoherent radiation. The effect of electron bunching on the
      radiation pattern is discussed. The mechanism of plasmon frequency-selective
      transition radiation is discovered.

PMID- 29041730
TI  - Multi-pass-cell-based nonlinear pulse compression to 115 fs at 7.5 uJ pulse
      energy and 300 W average power.
AB  - We demonstrate nonlinear pulse compression by multi-pass cell spectral broadening
      (MPCSB) from 860 fs to 115 fs with compressed pulse energy of 7.5 uJ, average
      power of 300 W and close to diffraction-limited beam quality. The transmission of
      the compression unit is >90%. The results show that this recently introduced
      compression scheme for peak powers above the threshold for catastrophic self
      focusing can be scaled to smaller pulse energies and can achieve a larger
      compression factor than previously reported. Good homogeneity of the spectral
      broadening across the beam profile is verified, which distinguishes MPCSB among
      other bulk compression schemes.

PMID- 29041729
TI  - Approaching the diffraction-limited, bandwidth-limited Petawatt.
AB  - J-KAREN-P is a high-power laser facility aiming at the highest beam quality and
      irradiance for performing state-of-the art experiments at the frontier of modern
      science. Here we approached the physical limits of the beam quality: diffraction
      limit of the focal spot and bandwidth limit of the pulse shape, removing the
      chromatic aberration, angular chirp, wavefront and spectral phase distortions. We
      performed accurate measurements of the spot and peak fluence after an f/1.3 off
      axis parabolic mirror under the full amplification at the power of 0.3 PW
      attenuated with ten high-quality wedges, resulting in the irradiance of ~1022
      W/cm2 and the Strehl ratio of ~0.5.

PMID- 29041731
TI  - Deep subwavelength interference lithography with tunable pattern period based on
      bulk plasmon polaritons.
AB  - Interference lithography based on surface plasmon polaritons has been proven to
      break the diffraction limit and deliver the high imaging resolution. However,
      most previously reported studies suffer from the inflexible pattern pitch for a
      certain structure ascribed to fixed excitation mode, which limits the
      applications in micro-/nano- fabrications. In this work, the large area deep
      subwavelength interference lithography with tunable pattern period based on bulk
      plasmon polaritons (BPPs) is proposed. By simply tuning the incident angle, the
      spatial frequencies of the selected BPPs modes squeezed through hyperbolic
      metamaterial changes correspondingly. As a result, the pitch of the interference
      pattern is continuously altered. The results demonstrate that one-dimensional and
      two-dimensional periodic patterns with pitch resolution ranging from 45 nm
      (~lambda/10) to 115 nm (~lambda/4) can be generated under 436 nm illumination.
      Additionally, the general method of designing such an interference lithography
      system is also discussed, which can be used for nanoscale fabrication in this
      fashion.

PMID- 29041732
TI  - Mode-locked Ho-doped laser with subsequent diode-pumped amplifier in an all-fiber
      design operating at 2052 nm.
AB  - We present a mode-locked holmium-doped all-fiber soliton laser operating in the
      2052 nm wavelength range. The ultrashort pulse oscillator is simultaneously self
      providing 1950-nm radiation for efficient in-band pumping in a subsequent thulium
      /holmium-doped fiber tandem amplifier. More than 76 nJ-pulses for Ho:YLF or
      Ho:YVO4 amplifier seeding have been achieved.

PMID- 29041733
TI  - Real and virtual propagation dynamics of angular accelerating white light beams.
AB  - Accelerating waves have received significant attention of late, first in the
      optical domain and later in the form of electron matter waves, and have found
      numerous applications in non-linear optics, material processing, microscopy,
      particle manipulation and laser plasma interactions. Here we create angular
      accelerating light beams with a potentially unlimited acceleration rate. By
      employing wavelength independent digital holograms for the creation and
      propagation of white light beams, we are able to study the resulting propagation
      in real and virtual space. We find that dephasing occurs for real propagation and
      that this can be compensated for in a virtual propagation scheme when single
      plane dynamics are important. Our work offers new insights into the propagation
      dynamics of such beams and provides a versatile tool for further investigations
      into propagating structured light fields.

PMID- 29041734
TI  - Active sparse aperture imaging using independent transmitter modulation with
      improved incoherent Fourier ptychographic algorithm.
AB  - Optical sparse aperture imaging shows great promise for the next generation of
      high resolution systems. In this paper, we propose and demonstrate an active
      sparse aperture imaging approach using independent transmitter modulation to
      digitally overcome phasing errors, correct aberrations, and further improve
      resolution. The reported imaging scheme consists of a general sparse aperture
      system and an active illumination unit, specifically an independent pattern
      projector. A series of raw images are captured with the projector scanned to
      illuminate the object. Based on the acquired data set, the improved incoherent
      Fourier ptychographic algorithm is utilized to reconstruct sparse aperture images
      with distortions removed and contrast enhanced. Furthermore, thanks to
      illumination pattern modulation, higher resolution beyond the diffraction limit
      of the synthetic aperture system is gained as a benefit. Good-quality and higher
      resolution sparse aperture imagery obtained by employing our proposed technique
      in both simulation and experiment demonstrates the effectiveness. The reported
      approach may provide new insights to address the phasing and image restoration
      problems of sparse aperture systems in the transmitting path rather than only in
      the receiving path.

PMID- 29041735
TI  - Analysis of spurious diffraction orders of computer-generated hologram in
      symmetric aspheric metrology.
AB  - Computer-generated hologram (CGH) has been widely used as a wavefront compensator
      in symmetric aspheric metrology. As a diffractive element, it generates different
      diffraction orders, but only the 1st-order diffraction is used to test aspheric
      surface. The light from spurious diffraction orders (SDO) will produce many high
      frequency fringes in interferogram and reduce measurement accuracy. In this
      paper, we regard the CGH null system as an imaging system and develop an
      aberration model in Seidel formalism to analyze the SDO. This model has the
      advantage to address the difference between the SDO (k1, k2) and (k2, k1). We
      consider the effect of the pupil distortion so that our model can analyze the SDO
      with a large pupil distortion. We derive the condition to ensure the 2nd-order
      and 4th-order aberrations have the same sign and calculate the minimum defocused
      distance (power carrier frequency) of CGH. According to the marginal-ray heights
      (h1andh3) on the CGH in the first and second passes, we determine the condition
      that the SDO covers the whole CGH in the second pass. We analyze the SDO of 4 CGH
      designs and compare the results from our aberration model with these from real
      ray trace. These results validate that our aberration model is feasible whether
      the aspheric part is convex or concave and whether CGH is inside or outside the
      focus of the transmission sphere.

PMID- 29041736
TI  - Investigation of ultra-broadband terahertz generation from sub-wavelength lithium
      niobate waveguides excited by few-cycle femtosecond laser pulses.
AB  - The generation of coherent, ultra-broadband terahertz (THz) radiation pulses
      spanning more than a few octaves is vital to understanding the ultrafast response
      of elementary excitations, molecules, nanostructures, materials, and explore
      device functionality across a wide spectrum. In this work, we use 2D finite
      difference time-domain simulations to show that ultra-broadband (0.18-106 THz)
      Cherenkov radiation can be produced from SiO2:MgO-LiNbO3:SiO2 waveguides having
      core dimensions that are sub-wavelength with respect to the optical pump pulse
      being guided. These sub-wavelength core dimensions allow the ultra-broad
      Cherenkov radiation to be emitted at an angle between 47.2 degrees  and 47.5
      degrees  (dictated by the Si cladding layer dispersion), making these waveguide
      structures superior to the THz generation arrangements in bulk MgO-LiNbO3
      crystals. When excited by a 7 fs, 780 nm laser pulse having an energy of 2 nJ, a
      300 um-long waveguide with transverse core dimensions of 500 nm * 2 mm can
      generate a sub-ps, kV/cm electric field pulse. Unlike THz pulse generation in
      bulk MgO-LiNbO3 crystals, having sub-wavelength core dimensions reduce the
      absorption from the MgO-LiNbO3 reststrahlen bands. These sub-wavelength SiO2:MgO
      LiNbO3:SiO2 waveguides are ideal for on-chip applications that require ultra
      broadband, compact THz sources.

PMID- 29041737
TI  - Synchronous model-based approach for wavefront sensorless adaptive optics system.
AB  - In this paper, an aberration correction algorithm for wavefront sensorless
      adaptive optics system is presented, which is based on the approximately linear
      relation between the mean square of the aberration gradients and the second
      moment of far-field intensity distribution. To demonstrate algorithm's
      performance, an experiment system of aberration corrections for Fresnel zone
      plates imaging is set up. The correction results show the excellent performance
      of this method in correction speed, and correction capability. Comparing with
      conventional stochastic parallel gradient descent (SPGD) algorithm, the
      correction speed with this method is improved about four times for the similar
      correction effect.

PMID- 29041738
TI  - Highly reflective nanofiber films based on electrospinning and their application
      on color uniformity and luminous efficacy improvement of white light-emitting
      diodes.
AB  - Based on electrospinning technology, in this study, we fabricated poly(lactic-co
      glycolic acid) (PLGA) nanofiber films with high reflectivity and scattering
      properties. Various films with different thicknesses and fiber diameters were
      fabricated by changing the electrospinning time and solution concentration,
      respectively. Detailed optical measurements demonstrate that the film reflectance
      and scattering ability increase with the thickness, whereas fiber diameter
      contributes little to both properties. With optimized film thickness and fiber
      diameter, nanofiber films feature whiteness with a reflectance of 98.8% compared
      to the BaSO4 white plate. Furthermore, when deposited on the reflector surface of
      a remote phosphor-converted light-emitting diode lamp, nanofiber films witness a
      correlated color temperature deviation decrease from 8880 K to 1407 K and a
      luminous efficiency improvement of 11.66% at 350 mA. Therefore, the nanofiber
      films can be applied in lighting systems as a highly reflective coating to
      improve their light efficacy and quality.

PMID- 29041739
TI  - Measurement of resonant bend loss in anti-resonant hollow core optical fiber.
AB  - We present the results of measurements of resonant spectral bend loss using a
      novel apparatus in a series of hollow core anti-resonant optical fibers,
      important for their applications in the delivery of industrial power ultra-short
      laser pulses. The measured bend losses exhibit clear wavelength-bend diameter
      resonances. We demonstrate, in good agreement with theoretical analysis, that the
      sensitivity to bend diameter (in terms of minimum bend radii) is dependent on the
      ratio between cladding and core structure size. By decreasing the cladding
      capillary diameter: core diameter ratio from 0.70 to 0.43 the minimum bend
      diameter is decreased from >160 mm to ~15 mm at a wavelength of 800 nm.
      Furthermore it is demonstrated that the exact position of the loss bands is
      highly dependent on the orientation of the fiber structure with the bend plane.

PMID- 29041740
TI  - Backside emission leaky-mode modulators.
AB  - We report on an advancement to leaky-mode modulators that allows for backside
      emission from the device. This is accomplished by adding a high spatial frequency
      surface relief grating (~300 nm period) to the backside of the modulator. The
      outcome being a theoretical arbitrary increase in usable output aperture, at the
      cost of angular deflection. Using backside emission, it is now possible for leaky
      mode modulators to be used to create transparent, holographic, direct-view near
      eye displays.

PMID- 29041741
TI  - Editorial: Optics Express - Growing Up.
AB  - The second Editor-in-Chief of Optics Express tells about the extraordinary growth
      of the journal from 2002 to 2006 and speculates on why it happened.

PMID- 29041742
TI  - Ag gyrus-nanostructure supported on graphene/Au film with nanometer gap for ideal
      surface enhanced Raman scattering.
AB  - The physical phenomenon, surface-enhanced Raman scattering (SERS), is mainly
      based on the local electromagnetic fields enhancement located at the nano-gaps
      between metal nanostructures attributed to localized surface plasmon resonance.
      Therefore, nano-gaps are very important for obtaining high-density hot spots and
      optimal and uniform SERS signals. However, it remains a challenge to form the
      three-dimensional ultra-narrow nano-gaps. Here, a gyrus-inspired Gyrus-SERS
      substrate was fabricated with the nanostructure of Ag gyrus/graphene/Au film
      using an extremely simple method. The lateral and vertical hot spots respectively
      were obtained from the dense nano-gaps (~3 nm) between gyrus and the coupling of
      Ag gyrus and Au film in bilayer graphene nano-gaps (0.68 nm), which were
      demonstrated in experiment and theory. The proposed Gyrus-SERS platform performs
      an excellent SERS activity (EF~5 * 109), high sensitivity (the minimum detected
      concentration of R6G and CV respectively is 10-13 and 10-12 M), and outstanding
      reproducibility (RSD~7.11%). For practical application, the in situ detection of
      Malachite green (MG) residue on prawn skin was executed using the prepared
      flexible Gyrus-SERS substrate, which shows the wide potential in food safety
      field.

PMID- 29041743
TI  - Ultrafast laser inscription in ZBLAN integrated optics chips for mid-IR beam
      combination in astronomical interferometry.
AB  - Astronomical interferometry is a unique technique that allows observation with
      angular resolutions on the milliarcsec scale by combining the light of several
      apertures hundreds of meters apart. The PIONIER and GRAVITY instruments at the
      Very Large Telescope Interferometer have demonstrated that silica-based
      integrated optics (IO) provide a small-scale and highly stable solution for the
      interferometric beam combination process. Yet, important science cases such as
      exoplanet hunting or the spectroscopic characterization of exoplanetary
      atmospheres are favorable for observation in the mid-IR, namely the atmospheric
      windows L and L' band (3-4 um), a wavelength range that is not covered by
      conventional silica-based IO. Here, we propose laser-inscribed IO 2*2 couplers in
      ZBLAN and experimentally assess the critical properties of the component for
      broadband mid-IR interferometry. We measure the splitting ratio over the 2.5 to
      5.0 um range and find excellent broadband contrast over the L (3.1-3.6 um) and L'
      (3.6 - 4.0 um) bands. Furthermore, we quantify the dispersion properties of the
      coupler and find a phase variation as low as 0.02 rad across the L and L' band,
      respectively. By optimizing the NA of our injection beam, we measured a very high
      total throughput of 58% over the L band including Fresnel reflection and coupling
      losses. We also compare our findings to recent advances in mid-IR IO in GLS and
      discuss its advantages and disadvantages for the implementation in future mid-IR
      interferometers.

PMID- 29041744
TI  - Volume holographic recording in Irgacure 784-doped PMMA photopolymer.
AB  - Photoinitiator plays a crucial role on photopolymer. Unlike photoinitiator
      phenanthrenequinone (PQ), the solubility of Irgacure 784 dissolved in MMA is very
      high. In this paper, we use Irgacure 784 as photoinitiator doped in poly(methyl
      methacrylate)(PMMA)to make a bulk photopolymer with high photoinitiator
      concentration for holographic data storage. The effect of concentration of
      photoinitiator and record intensity are experimentally investigated. The results
      reveal the material has an optimum condition in holographic recording. A
      comparison between our material and the material of PQ doped PMMA is carried out
      by experiment. It is found that our material has better performance on
      diffraction efficiency, refractive index modulation and recording sensitivity.
      Besides, this material also has polarization sensitivity, which can be applied to
      polarization holography. With the capacity of recording polarization holography
      and conventional intensity holography simultaneously, the Irgacure 784 doped PMMA
      material is expected to be applied in holographic data storage.

PMID- 29041745
TI  - 1.5 MUm polarization coherent lidar incorporating time-division multiplexing.
AB  - Atmospheric depolarization ratio and wind velocity are measured simultaneously by
      a single versatile coherent Doppler lidar (CDL). Backscattering components at
      parallel and perpendicular polarization states are obtained by using a single
      balanced detector, adopting time-division multiplexing technique. Thus systematic
      error induced by the non-uniform response of different detectors in traditional
      lidars is avoided. The operation mode of the instrument can be switched from
      polarization CDL to traditional CDL by the user depending on atmospheric
      conditions and desired performance. As demonstrated, the perpendicular component
      of the backscattering, usually wasted, not only can be used to retrieve the ADR,
      but also can be used to improve the carrier to noise ratio in wind detection. In
      the traditional mode, given a tolerance of 0.5 m/s precision, a detection range
      of 6 km is achieved by using a 300 ns laser pulse with energy of 100 MUJ, where
      the temporal and spatial resolution of 2 s and 60 m, respectively. Continuous
      wind detection of the atmospheric boundary layer over 26 hours is presented to
      demonstrate the robustness and stability of the system. Dynamic evolution and
      wind structure are recorded.

PMID- 29041746
TI  - Ultra-compact optical zoom endoscope using solid tunable lenses.
AB  - We report an ultra-compact optical zoom endoscope containing two tunable Alvarez
      lenses. The two tunable lenses are controlled synchronously by piezoelectric
      benders to move in directions perpendicular to the optical axis to achieve
      optical zoom while keeping images in clear focus without moving the scope. The
      piezoelectric benders are arranged circumferentially surrounding the endoscope
      optics with a diameter about 2 mm, which results in an ultra-compact form. The
      demonstrated endoscope is capable of optical zoom close to 3 * from field of view
      (FOV) 50 degrees  to 18 degrees  continuously with the required movements for its
      constituent optical elements less than 110 MUm. Such optical zoom endoscopes may
      find their potential uses in healthcare and industrial inspection systems.

PMID- 29041747
TI  - Polarization-dependent electromagnetic responses in an A-shape metasurface.
AB  - We numerically and experimentally demonstrate polarization-dependent terahertz
      responses in a proposed metasurface of A-shape resonators. With the horizontal
      polarization incidence, the observed transmission window is formed by two
      resonance dips, corresponding to the inductive-capacitive resonance at the lower
      frequency and the high-order antisymmetric resonance at a higher frequency,
      respectively. When the incident wave is perpendicularly polarized, the
      transmission window arises from the plasmon-induced transparency spectral
      response. The origin of the polarization-sensitive resonance properties is
      revealed by mapping the electric field and terahertz-induced surface current in
      the proposed metamaterials. Moreover, the influence of the geometry of the A
      shape microstructures on the transmission spectra is analyzed. These polarization
      dependent metamaterials may provide more degrees of freedom in tuning the
      electromagnetic responses, thus offering a path toward robust metamaterials
      design.

PMID- 29041748
TI  - Optical switch compatible with wavelength division multiplexing and mode division
      multiplexing for photonic networks-on-chip.
AB  - We propose a 2 * 2 multimode optical switch, which is composed of two mode de
      multiplexers, n 2 * 2 single-mode optical switches where n is the number of the
      supported spatial modes, and two mode multiplexers. As a proof of concept,
      asymmetric directional couplers are employed to construct the mode multiplexers
      and de-multiplexers, balanced Mach-Zehnder interferometer is utilized to
      construct the 2 * 2 single-mode optical switches. The fabricated silicon 2 * 2
      multimode optical switch has a broad optical bandwidth and can support four
      spatial modes. The link-crosstalk for all four modes is smaller than -18.8 dB.
      The inter-mode crosstalk for the same optical link is less than -22.1 dB. 40 Gbps
      data transmission is performed for all spatial modes and all optical links. The
      power penalties for the error-free switching (BER<10-9) at 25 Gbps are less than
      1.8 dB for all channels at the wavelength of 1550 nm. The power consumption of
      the device is 117.9 mW in the "cross" state and 116.2 mW in the "bar" state. The
      switching time is about 21 MUs. This work enables large-capacity multimode
      photonic networks-on-chip.

PMID- 29041749
TI  - Surface vector plasmonic lattice solitons in semi-infinite graphene-pair arrays.
AB  - We investigate the surface vector plasmonic lattice solitons (PLSs) in semi
      infinite graphene-pair arrays (GPAs). The surface vector PLSs are composed of two
      components which are associated with different band gaps. Both components undergo
      mutual self-trapping at the boundary of the semi-infinite structure when the self
      focusing nonlinearity of graphene and the light diffraction reach a balance.
      Thanks to the strong confinement of SPPs, the surface vector PLSs can be squeezed
      into a deep-subwavelength width of ~0.003lambda. By comparing with bulk solitons,
      the surface PLSs are more readily to excite by external waves and more sensitive
      to the surrounding environment. The study may develop promising applications in
      all-optical switching devices and optical sensors on deep-subwavelength scale.

PMID- 29041750
TI  - Continuous-wave THz vector imaging system utilizing two-tone signal generation
      and self-mixing detection.
AB  - We propose and demonstrate a continuous-wave vector THz imaging system utilizing
      a photonic generation of two-tone THz signals and self-mixing detection. The
      proposed system measures amplitude and phase information simultaneously without
      the local oscillator reference or phase rotation scheme that is required for
      heterodyne or homodyne detection. In addition, 2pi phase ambiguity that occurs
      when the sample is thicker than the wavelength of THz radiation can be avoided.
      In this work, THz signal having two frequency components was generated with a uni
      traveling-carrier photodiode and electro-optic modulator on the emitter side and
      detected with a Schottky barrier diode detector used as a self-mixer on the
      receiver side. The proposed THz vector imaging system exhibited a 50-dB signal to
      noise ratio and 0.012-rad phase fluctuation with 100-MUs integration time at 325
      GHz. With the system, we demonstrate two-dimensional THz phase contrast imaging.
      Considering the recent use of two-dimensional arrays of Schottky barrier diodes
      as a THz image sensor, the proposed system is greatly advantageous for realizing
      a real-time THz vector imaging system due to its simple receiver configuration.

PMID- 29041751
TI  - Reduction of modal evolution fluctuation in 2-LP mode optical time domain
      reflectometry.
AB  - This paper describes theoretical and experimental investigations of an optical
      time domain reflectometry (OTDR) that conducts measurements in the 2-LP mode
      region of the fiber under test. Rayleigh backscattering amplitude coefficients
      from the HE11 mode to higher-order vector modes are analyzed to clarify the
      evolution in the state of polarization of the backscattered vector modes with
      respect to that of the probe HE11 mode. Based on the analysis, we then propose a
      technique for reducing amplitude fluctuations in the OTDR traces attributed to
      intensity distribution evolution of the LP11 mode. A proof-of-concept
      demonstration is performed on optical fibers in the laboratory and field
      environments, and the measured results confirm its usefulness.

PMID- 29041752
TI  - Polarization squeezing at the audio frequency band for the Rubidium D1 line.
AB  - A 2.8-dB polarization squeezing of the Stokes operatorS^2for the rubidium D1 line
      (795 nm) is achieved, with the lowest squeezing band at an audio frequency of 2.6
      kHz. It is synthetized by a bright coherent beam and a squeezed vacuum, which are
      orthogonally polarized and share same frequency. Two methods are applied to
      support the optical parametric oscillator: an orthogonally-polarized locking beam
      that precludes residual unwanted interference and quantum noise locking method
      that locks the squeezing phase. Besides, the usage of low noise balanced
      detector, mode cleaner and the optical isolator helped to improve the audio
      frequency detection. The squeezing level is limited by absorption-induced losses
      at short wavelengths, which is 397.5 nm. The generated polarization squeezed
      light can be used in a quantum enhanced magnetometer to increase the measurement
      sensitivity.

PMID- 29041753
TI  - Triple band frequency generator based on an optoelectronic oscillator with low
      phase noise.
AB  - A triple band frequency generator based on the optoelectronic oscillator (OEO)
      with low phase noise has been proposed and experimentally demonstrated. In this
      novel scheme, the phase-coherent triple band frequency in C, Ku and K bands can
      be achieved simultaneously by biasing the first modulator in the oscillation loop
      at the minimum transmission point (MITP) and the second modulator near the MITP
      with a small deviation. In the proof-of-concept experiment, the triple band
      frequency signals at 5.36, 16.08 and 21.44 GHz are generated with the phase noise
      of -123.32, -113.68 and -111.19 dBc/Hz at 10 kHz offset frequency, respectively.
      The proposed scheme provides a novel strategy for phase-coherent multi-band
      frequency and low phase noise signals generation, which can be potentially used
      in the multi-function and multi-band frequency electrical systems.

PMID- 29041754
TI  - Wave-vector and polarization dependent impedance model for a hexagonal periodic
      metasurface exemplified through finite-difference time-domain simulations.
AB  - An isotropic impedance sheet model is proposed for a loop-type hexagonal periodic
      metasurface. Both frequency and wave-vector dispersion are considered near the
      resonance frequency. Therefore both the angle and polarization dependences of the
      metasurface impedance can be properly and simultaneously described in our model.
      The constitutive relation of this model is transformed into auxiliary
      differential equations which are integrated into the finite-difference time
      domain algorithm. Finally, a finite large metasurface sample under oblique
      illumination is used to test the model and the algorithm. Our model and algorithm
      can significantly increase the accuracy of the homogenization methods for
      modeling periodic metasurfaces.

PMID- 29041755
TI  - Feedforward linearization for RF photonic link with broadband adjustment-free
      operation.
AB  - Linearization of radio frequency (RF) photonic link is critical for advance
      applications because a nonlinear transfer function of electro-optic modulation
      limits link dynamic range. Although numerous approaches to suppress third order
      intermodulation distortion (IMD3) have been demonstrated in previous literatures,
      many schemes need attendant link optimization when an input RF carrier frequency
      is tuned over a broad band. In this paper, we propose and demonstrate an
      adjustment-free linearization approach where high dynamic range could be kept
      during RF frequency tuning. After a regular low-biased external modulation, the
      "distortion information" is extracted by a baseband receiver, which then
      modulates the optically-carried RF signal again. Such distortion extraction and
      correction is baseband and is independent on the frequency of the RF frequency.
      The proposal is theoretically analyzed and simulated. In an experiment, IMD3
      nonlinear spurs are suppressed over around 60 dB uniformly under typical input RF
      power, while the carrier is tuned from 4 GHz to 12 GHz. The spurious-free dynamic
      range (SFDR) is kept around 125 dB within 1-Hz bandwidth without attendant
      optimization of link parameters.

PMID- 29041756
TI  - Dual tunable plasmon-induced transparency based on silicon-air grating coupled
      graphene structure in terahertz metamaterial.
AB  - A graphene plasmonic structure consists of three graphene layers mingled with a
      silicon-air grating is proposed. We theoretically predict and numerically
      simulate the plasmon-induced transparency effect in this system at terahertz
      wavelengths, and a dual plasmon-induced transparency peaks can be successfully
      tuned by virtually shifting the desired Fermi energy on graphene layers. We
      investigate the surface plasmon dispersion relation by means of analytic
      calculations, and we can achieve the numerical solution of propagation constant
      got by the dispersion relation. A suitable theoretical model is established to
      study spectral features in the plasmonic graphene system, and the theoretical
      results agree well with the simulations. The proposed model and findings may
      provide guidance for fundamental research of highly tunable optoelectronic
      devices.

PMID- 29041757
TI  - Improvement of the temporal and spatial contrast of the nonlinear Fourier-filter.
AB  - Recently a novel method called nonlinear Fourier-filtering was suggested for
      temporal and spatial cleaning of high-brightness laser pulses. In this paper
      experimental demonstration of the associated spatial filtering of this method and
      significant improvement of the temporal filtering feature are presented. The
      formerly found limit of ~103 for the temporal contrast improvement is identified
      as diffraction effects caused by the limited numerical aperture of imaging. It is
      shown by numerical simulation that proper apodization of the object can lead to
      sufficiently higher limit (>108). Using an advanced experimental arrangement the
      improvement of >2 orders of magnitude is experimentally verified in the
      ultraviolet and an indirect proof is presented that the background caused by the
      optical arrangement is reduced below 10-7.

PMID- 29041758
TI  - Total momentum transfer produced by the photons of a multi-pass laser beam as an
      evident avenue for optical and mass metrology.
AB  - The use of the radiation pressure of a laser field, as an effect of the momentum
      transfer of the absorbed and re-emitted photons, suggests rather a complementary
      than an alternative possibility for metrology to generate calibration forces or
      to calibrate the optical power directly traceable to the International System of
      Units (SI). This paper reports a method and experimentally measured evidence on
      options to extend the effective use of radiation pressure for generating optical
      forces in the sub-microNewton (MUN) range. Among other features and results
      presented, we emphasize the variability in controlling the accuracy of these
      forces through the proper utilization of the power of a multi-pass laser beam
      (semi- or completely) locked within confined systems. The direct measurements of
      these forces, augmented due to the partial or total momentum transfer of the
      photons of a multi-pass laser beam extended from several hundreds of picoNewton
      (pN) up to sub-MUN range for the same power of laser source, are done by a
      precision force measurement system and compared with basic theoretical
      computations. We also discuss the opportunities to probe the fundamental physical
      limits associated with this method and to the considerable extent other competing
      contributing effects that might be regarded as sources of errors in metrological
      tasks.

PMID- 29041759
TI  - Assembly and alignment method for optimized spatial resolution of off-axis three
      mirror fore optics of hyperspectral imager.
AB  - A fore optics for the hyperspectral spectrometer is designed, manufactured,
      assembled, and aligned. The optics has a telecentric off-axis three-mirror
      configuration with a field of view wider than 14 degrees and an f-number as small
      as 2.3. The primary mirror (M1) and the secondary mirror (M2) are axially
      symmetric aspheric surfaces to minimize the sensitivity. The tertiary mirror (M3)
      is a decentered aspheric surface to minimize the coma and astigmatism aberration.
      The M2 also has a hole for the slit to maintain the optical performance while
      maximizing the telecentricity. To ensure the spatial resolution performance of
      the optical system, an alignment procedure is established to assemble and align
      the entrance slit of the spectrometer to the rear end of the fore optics. It has
      a great advantage to confirm and maintain the alignment integrity of the fore
      optics module throughout the alignment procedure. To perform the alignment
      procedure successfully, the precision movement control requirements are
      calculated and applied. As a result, the alignment goal of the RMS wave front
      error (WFE) to be smaller than 90 nm at all fields is achieved.

PMID- 29041760
TI  - 10-m 9.51-Gb/s RGB laser diodes-based WDM underwater wireless optical
      communication.
AB  - The availability of the underwater wireless optical communication (UWOC) based on
      red (R), green (G) and blue (B) lights makes the realization of the RGB
      wavelength division multiplexing (WDM) UWOC system possible. By properly mixing
      RGB lights to form white light, the WDM UWOC system has prominent potentiality
      for simultaneous underwater illumination and high-speed communication. In this
      work, for the first time, we experimentally demonstrate a 9.51-Gb/s WDM UWOC
      system using a red-emitting laser diode (LD), a single-mode pigtailed green
      emitting LD and a multi-mode pigtailed blue-emitting LD. By employing 32
      quadrature amplitude modulation (QAM) orthogonal frequency division multiplexing
      (OFDM) modulation in the demonstration, the red-light, the green-light and the
      blue-light LDs successfully transmit signals with the data rates of 4.17 Gb/s,
      4.17 Gb/s and 1.17 Gb/s, respectively, over a 10-m underwater channel. The
      corresponding bit error rates (BERs) are 2.2 * 10-3, 2.0 * 10-3 and 2.3 * 10-3,
      respectively, which are below the forward error correction (FEC) threshold of 3.8
      * 10-3.

PMID- 29041761
TI  - Spectrally pure heralded single photons by spontaneous four-wave mixing in a
      fiber: reducing impact of dispersion fluctuations.
AB  - We model the spectral quantum-mechanical purity of heralded single photons from a
      photon-pair source based on nondegenerate spontaneous four-wave mixing taking the
      impact of distributed dispersion fluctuations into account. The considered photon
      pair-generation scheme utilizes pump-pulse walk-off to produce pure heralded
      photons and phase matching is achieved through the dispersion properties of
      distinct spatial modes in a few-mode silica step-index fiber. We show that fiber
      core-radius fluctuations in general severely impact the single-photon purity.
      Furthermore, by optimizing the fiber design we show that generation of single
      photons with very high spectral purity is feasible even in the presence of large
      core-radius fluctuations. At the same time, contamination from spontaneous Raman
      scattering is greatly mitigated by separating the single-photon frequency by more
      than 32 THz from the pump frequency.

PMID- 29041762
TI  - Electromagnetic behavior of spatial terahertz wave modulators based on
      reconfigurable micromirror gratings in Littrow configuration.
AB  - Efficient, high speed spatial modulators with predictable performance are a key
      element in any coded aperture terahertz imaging system. For spectroscopy, the
      modulators must also provide a broad modulation frequency range. In this study,
      we numerically analyze the electromagnetic behavior of a dynamically
      reconfigurable spatial terahertz wave modulator based on a micromirror grating in
      Littrow configuration. We show that such a modulator can modulate terahertz
      radiation over a wide frequency range from 1.7 THz to beyond 3 THz at a
      modulation depth of more than 0.6. As a specific example, we numerically
      simulated coded aperture imaging of an object with binary transmissive properties
      and successfully reconstructed the image.

PMID- 29041763
TI  - Novel OBI noise reduction technique by using similar-OBI estimation in optical
      multiple access uplink.
AB  - A novel optical beat interference (OBI) noise reduction technique for optical
      multiple access uplink using the same wavelength is presented. The OBI noise is
      estimated by similar-OBI and mitigated by subtracting estimated OBI noise using
      the digital signal processing technique. To derive similar-OBI, an RF clipping
      tone is transmitted out of signal band. We numerically and experimentally
      verified the validity of proposed OBI noise reduction method in orthogonal
      frequency division multiplexing access (OFDMA) passive optical network (PON)
      uplink where the OBI noise has been reduced and signal to noise ratio (SNR) has
      been improved from 4.4 dB to 10.6 dB.

PMID- 29041764
TI  - Energetic radially polarized few-cycle pulse compression in gas-filled hollow
      core fiber.
AB  - The compression of high-energy, radially polarized pulses in a gas-filled hollow
      core fiber (HCF) is theoretically studied. The simulation results indicate that a
      40-fs input pulse can be compressed to a full-width at half-maximum of less than
      9 fs when the pulse energy reaches 7.0 mJ with a transmission efficiency of more
      than 67% after propagating through a 1-m-long, 500-MUm diameter HCF filled with
      neon. Furthermore, the spatio-temporal intensity distributions of the compressed
      pulses with different initial input energies are studied, and the numerical
      results indicate that the spatio-temporal intensity distributions are more
      uniform for lower input pulse energies.

PMID- 29041765
TI  - Generation of two-temporal-mode photon states by vector four-wave mixing.
AB  - Photon pair states and multiple-photon squeezed states have many applications in
      quantum information science. In this paper, Green functions are derived for
      spontaneous four-wave mixing in the low- and high-gain regimes. Nondegenerate
      four-wave mixing in a strongly-birefringent medium generates signal and idler
      photons that are associated with only one pair of temporal (Schmidt) modes, for a
      wide range of pump powers and arbitrary pump shapes. The Schmidt coefficients
      (expected photon numbers) depend sensitively on the pump powers, and the Schmidt
      functions (shapes of the photon wavepackets) depend sensitively on the pump
      powers and shapes, which can be controlled.

PMID- 29041766
TI  - Image quality improvement of multi-projection 3D display through tone mapping
      based optimization.
AB  - An optical 3D screen usually shows a certain diffuse reflectivity or diffuse
      transmission, and the multi-projection 3D display suffers from decreased display
      local contrast due to the crosstalk of multi-projection contents. A tone mapping
      based optimizing method is innovatively proposed to suppress the crosstalk and
      improve the display contrast by minimizing the visible contrast distortions
      between the display light field and a targeted one with enhanced contrast. The
      contrast distortions are weighted according to the visibility predicted by the
      model of human visual system, and the distortions are minimized for the given
      multi-projection 3D display model that enforces constrains on the solution. Our
      proposed method can adjust parallax images or parallax video contents for the
      optimum 3D display image quality taking into account the display characteristics
      and ambient illumination. The validity of the method is evaluated and proved in
      experiments.

PMID- 29041767
TI  - High-sensitivity complex refractive index sensing based on Fano resonance in the
      subwavelength grating waveguide micro-ring resonator.
AB  - High-sensitivity complex refractive index sensing is proposed and experimentally
      demonstrated, favoring with sharp Fano resonance at 1550 nm wavelength based on
      subwavelength grating waveguide (SWG) micro-ring resonator. The micro-ring is
      composed by trapezoidal silicon pillars with subwavelength period to enhance the
      light-analyte overlap and get high quality factor as well. One straight SWG
      waveguide is side coupled with the micro-ring, which is specially designed to
      produce partial Fabry-Perot (FP) effect. Due to the interaction of resonant state
      of micro-ring and partial FP effect in straight waveguide, a sharp asymmetrical
      Fano resonance is formed at 1550 nm wavelength. Benefit from the large light
      analyte overlap of the SWG waveguide structure and the sharp asymmetrical Fano
      resonance in spectrum, high theoretical sensitivities of 366 nm/RIU and 9700/RIU
      can be realized for the real part (n) and the imaginary part (kappa) of
      refractive index respectively. We also experimentally demonstrate the sensing for
      glucose solution concentrations, and high experimental sensitivity of 363nm/RIU
      is obtained for n, and for kappa the experimental results are also in well
      agreement with the simulation results.

PMID- 29041768
TI  - Dissipative soliton resonance in Bismuth-doped fiber laser.
AB  - We experimentally demonstrate the generation of dissipative soliton resonance
      (DSR) in a passively mode-locked Bi-doped fiber ring laser based on nonlinear
      polarization rotation (NPR) technique. The DSR with the central wavelength of
      1169.5 nm has a repetition rate of 343.7 kHz. By purely increasing the pump
      power, the DSR evolves from Gaussian shape to rectangular shape with the duration
      extending from 2.1 ns to 13.1 ns, while keeping the pulse amplitude and the 3-dB
      spectrum bandwidth almost constant. The single-pulse energy reaches 24.82 nJ.
      Furthermore, we construct a lumped model to reproduce the mode-locking process
      and the traits of the DSR pulse. The obtained results indicate that it could
      achieve higher pulse energy in mode-locked Bi-doped fiber laser by generating
      DSR.

PMID- 29041769
TI  - High mechanical bandwidth fiber-coupled Fabry-Perot cavity.
AB  - Fiber-based optical microcavities exhibit high quality factor and low mode volume
      resonances that make them attractive for coupling light to individual atoms or
      other microscopic systems. Moreover, their low mass should lead to excellent
      mechanical response up to high frequencies, opening the possibility for high
      bandwidth stabilization of the cavity length. Here, we demonstrate a locking
      bandwidth of 44 kHz achieved using a simple, compact design that exploits these
      properties. Owing to the simplicity of fiber feedthroughs and lack of free-space
      alignment, this design is inherently compatible with vacuum and cryogenic
      environments. We measure the transfer function of the feedback circuit (closed
      loop) and the cavity mount itself (open-loop), which, combined with simulations
      of the mechanical response of our device, provide insight into underlying
      limitations of the design as well as further improvements that can be made.

PMID- 29041770
TI  - Ultra-efficient Raman amplifier in methane-filled hollow-core fiber operating at
      1.5 MUm.
AB  - We report on what is, to the best of our knowledge, the first ultra-efficient 1.5
      MUm Raman amplifier in a methane-filled anti-resonance hollow-core fiber. A 1.5
      MUm single frequency seed laser is coupled into the hollow-core fiber together
      with a 1064 nm pulsed pump laser using a shortpass dichromic mirror, and then
      amplified by stimulated Raman scattering of methane. A maximum optical-to-optical
      conversion efficiency of 66.4% has been obtained, resulting in a record near
      quantum-limit efficiency of 96.3% in a 2 m long hollow-core fiber filled with
      only 2 bar methane gas. This kind of gas filled hollow-core Raman amplifier
      provides a potential method to obtain high efficiency mid-infrared laser sources
      with low threshold and narrow linewidth in various applications.

PMID- 29041771
TI  - Enhancing ultraviolet spontaneous emission with a designed quantum vacuum:
      erratum.
AB  - We present a correction to parts of Fig. 5, Fig. 6 and Fig. 7, relating to the
      Purcell factors and Lamb shifts, due to an incorrect renormalization used in our
      custom Fortran code. The resulting corrections to some of the Q-factors are
      large, but do not affect the conclusions of the original manuscript.

PMID- 29041772
TI  - Randomized apertures: high resolution imaging in far field: erratum.
AB  - We note a correction to Eq. (6) for [ Opt. Express25(15), 18296 (2017)].

PMID- 29041773
TI  - Total Synthesis of Resiniferatoxin Enabled by Radical-Mediated Three-Component
      Coupling and 7-endo Cyclization.
AB  - Resiniferatoxin (1) belongs to a daphnane diterpenoid family and has strong
      agonistic effects on TRPV1, a transducer of noxious temperature and chemical
      stimuli. The densely oxygenated trans-fused 5/7/6-tricarbocycle (ABC-ring) of 1
      presents a daunting challenge for chemical synthesis. Here we report the
      development of a novel radical-based strategy for assembling 1 from three
      components: A-ring 9, allyl stannane 18b, and C-ring 17b. The 6-membered 17b,
      prepared from d-ribose derivative 19, was designed to possess the caged
      orthoester structure with alpha-alkoxy selenide as a radical precursor. Upon
      treatment of 17b with 18b, 9, and V-40, the potently reactive alpha-alkoxy
      bridgehead radical was generated from 17b and then sequentially coupled with 9
      and 18b to yield 16b. This first radical reaction formed the hindered C9,10
      linkage between the A and C-rings and extended the C4-chain on the A-ring in a
      stereoselective fashion. After derivatization of 16b into 15, the remaining 7
      membered B-ring was cyclized in the presence of n-Bu3SnH and V-40 by utilizing
      the xanthate on the C-ring as the radical precursor and the allylic
      dithiocarbonate as the terminator. The second radical reaction thus enabled not
      only the 7-endo cyclization but also construction of the C8-stereocenter and the
      C6-exo olefin. Tricycle 14 was elaborated into the targeted 1 by a series of
      highly optimized chemoselective reactions. The present total synthesis of 1
      demonstrates the advantages of radical reactions for linking hindered bonds
      within carbocycles without damaging preexisting functionalities, thereby offering
      a new strategic design for multistep target-oriented synthesis.

PMID- 29041774
TI  - Enforced Tubular Assembly of Electronically Different Hexakis(m-Phenylene
      Ethynylene) Macrocycles: Persistent Columnar Stacking Driven by Multiple Hydrogen
      Bonding Interactions.
AB  - Hexakis(m-phenylene ethynylene) (m-PE) macrocycles 1-4, sharing the same hydrogen
      bonding side chains but having backbones of different electronic properties, are
      designed to probe the effectiveness of multiple H-bonding interactions in
      enforcing columnar assemblies. 1H NMR, absorption, fluorescence, and circular
      dichroism (CD) spectroscopy indicate that, compared with analogous macrocycles
      that self-associate based on aromatic stacking which is highly sensitive to the
      electronic nature of the macrocyclic backbones, macrocycles 1-4 all exhibit
      strong aggregation down to the micromolar (MUM) concentrations in nonpolar
      solvents. Increasing solvent polarity quickly weakens aggregation. In THF and
      DMF, the macrocycles exist as free molecules. The observed solvent effects, along
      with the behavior of 5-F6 that cannot self-associate via H-bonding, confirm that
      H-bonding plays the dominating role in driving the self-association of 1-4. The
      backbone electronic nature does not change the self-assembling pattern common to
      1-4. Fluorescence and CD spectra confirm that macrocycles 1-4 assemble
      anisotropically, forming helical stacks in which adjacent molecules undergo
      relative rotation to place individual benzene residues in the favorable offset
      fashion. Columnar alignment of 1-4 is confirmed by atomic force microscopy (AFM),
      which resolves single tubes consisting of stacked macrocycles. In addition,
      macrocycles with backbones of different electronic properties are found to
      undergo heteroassociation, forming hybrid nanotubes. This study has demonstrated
      the generality of enforcing the alignment of shape-persistent macrocycles, which
      represents an invaluable addition to the small number of known tubular stacks
      capable of accommodating structurally varied molecular components and provides
      self-assembling nanotubes with inner pores allowing ready structural and
      functional modification.

PMID- 29041775
TI  - Lychee (Litchi chinensis Sonn.) Pulp Phenolic Extract Provides Protection against
      Alcoholic Liver Injury in Mice by Alleviating Intestinal Microbiota Dysbiosis,
      Intestinal Barrier Dysfunction, and Liver Inflammation.
AB  - Liver injury is the most common consequence of alcohol abuse, which is promoted
      by the inflammatory response triggered by gut-derived endotoxins produced as a
      consequence of intestinal microbiota dysbiosis and barrier dysfunction. The aim
      of this study was to investigate whether modulation of intestinal microbiota and
      barrier function, and liver inflammation contributes to the hepatoprotective
      effect of lychee pulp phenolic extract (LPPE) in alcohol-fed mice. Mice were
      treated with an ethanol-containing liquid diet alone or in combination with LPPE
      for 8 weeks. LPPE supplementation alleviated ethanol-induced liver injury and
      downregulated key markers of inflammation. Moreover, LPPE supplementation
      reversed the ethanol-induced alteration of intestinal microbiota composition and
      increased the expression of intestinal tight junction proteins, mucus protecting
      proteins, and antimicrobial proteins. Furthermore, in addition to decreasing
      serum endotoxin level, LPPE supplementation suppressed CD14 and toll-like
      receptor 4 expression, and repressed the activation of nuclear factor-kappaB p65
      in the liver. These data suggest that intestinal microbiota dysbiosis, intestinal
      barrier dysfunction, and liver inflammation are improved by LPPE, and therefore,
      the intake of LPPE or Litchi pulp may be an effective strategy to alleviate the
      susceptibility to alcohol-induced hepatic diseases.

PMID- 29041776
TI  - Trivalent Zirconium and Hafnium Metal-Organic Frameworks for Catalytic 1,4
      Dearomative Additions of Pyridines and Quinolines.
AB  - We report the quantitative conversion of [MIV6(MU3-O)4(MU3-OH)4Cl12]6- nodes in
      the MCl2-BTC metal-organic framework into the [MIII6(MU3-O)4(MU3-ONa)4H6]6- nodes
      in MIIIH-BTC (M = Zr, Hf; BTC is 1,3,5-benzenetricarboxylate) via bimetallic
      reductive elimination of H2 from putative [MIV6(MU3-O)4(MU3-OH)4H12]6- nodes. The
      coordinatively unsaturated MIIIH centers in MIIIH-BTC are highly active and
      selective for 1,4-dearomative hydroboration and hydrosilylation of pyridines and
      quinolines. This work demonstrated the potential of secondary building unit
      transformation in generating electronically unique and homogeneously inaccessible
      single-site solid catalysts for organic synthesis.

PMID- 29041777
TI  - Frequency Dependence of Low-Voltage Electrowetting Investigated by Impedance
      Spectroscopy.
AB  - An electrowetting-on-dielectric (EWOD) electrode was developed that facilitates
      the use of low alternating voltages (<=5 VAC). This allows online investigation
      of the frequency dependence of electrowetting by means of impedance spectroscopy.
      The EWOD electrode is based on a dielectric bilayer consisting of an anodic
      tantalum pentoxide (Ta2O5) thin film (d = 59.35 nm) with a high relative
      permittivity (epsilond = 26.3) and a self-assembled hydrophobic silane monolayer.
      The frequency dependence of electrowetting was studied using an aqueous MUL-sized
      sessile droplet on the planar EWOD electrode in oil. Experiments using
      electrochemical impedance spectroscopy and optical imaging indicate the frequency
      dependence of all three variables in the Young-Lippmann equation: the voltage
      drop across the dielectric layers, capacitance per unit area, and contact angle
      under voltage. The electrowetting behavior induced by AC voltages is shown to be
      well described by the Young-Lippmann equation for AC applications below a
      frequency threshold. Moreover, the dielectric layers act as a capacitor and the
      stored electrostatic potential energy is revealed to only partially contribute to
      the electrowetting.

PMID- 29041778
TI  - Electrolysis-Driven and Pressure-Controlled Diffusive Growth of Successive
      Bubbles on Microstructured Surfaces.
AB  - Control over the bubble growth rates forming on the electrodes of water-splitting
      cells or chemical reactors is critical with respect to the attainment of higher
      energy efficiencies within these devices. This study focuses on the diffusion
      driven growth dynamics of a succession of H2 bubbles generated at a flat silicon
      electrode substrate. Controlled nucleation is achieved by means of a single
      nucleation site consisting of a hydrophobic micropit etched within a micrometer
      sized pillar. In our experimental configuration of constant-current electrolysis,
      we identify gas depletion from (i) previous bubbles in the succession, (ii)
      unwanted bubbles forming on the sidewalls, and (iii) the mere presence of the
      circular cavity where the electrode is being held. The impact of these effects on
      bubble growth is discussed with support from numerical simulations. The time
      evolution of the dimensionless bubble growth coefficient, which is a measure of
      the overall growth rate of a particular bubble, of electrolysis-generated bubbles
      is compared to that of CO2 bubbles growing on a similar surface in the presence
      of a supersaturated solution of carbonated water. For electrolytic bubbles and
      under the range of current densities considered here (5-15 A/m2), it is observed
      that H2 bubble successions at large gas-evolving substrates first experience a
      stagnation regime, followed by a fast increase in the growth coefficient before a
      steady state is reached. This clearly contradicts the common assumption that
      constant current densities must yield time-invariant growth rates. Conversely,
      for the case of CO2 bubbles, the growth coefficient successively decreases for
      every subsequent bubble as a result of the persistent depletion of dissolved CO2.

PMID- 29041780
TI  - ACS Chemical Neuroscience: Most Cited Papers from 2016.

PMID- 29041781
TI  - Nursing students' perceptions of soft skills training in Ghana.
AB  - BACKGROUND: The quality of nursing care rendered today is markedly reducing and
      the amount of time spent with patients listening to and explaining issues
      concerning their conditions is gradually diminishing. The therapeutic touch and
      the listening ear of the nurse are no longer accessible to the patient.
      Understanding what non-technical skills are and their relevance for healthcare
      practitioners has become a new area of consideration. Although recent literature
      has highlighted the necessity of introducing soft skills training and assessment
      within medical education, nursing education is yet to fully embrace this skills
      training. OBJECTIVES: The aim of this study was to explore nursing students'
      understanding of the concept of soft skills and to acquire their perception on
      the need for soft skills training to promote quality nursing care. METHODS: A
      quantitative research design with descriptive and explorative strategies was
      used. One hundred and ten nursing students were sampled after permission to
      conduct the study was requested and obtained from the University of KwaZulu-Natal
      Ethics Committee. RESULTS: The results indicated that a majority (68.8%) of
      respondents understood the concept of soft skills and agreed with the definition
      of 'soft skills'. They furthermore agreed that soft skills should be part of the
      training that student nurses receive during their professional training.
      CONCLUSION: The study revealed that there is a need for nursing students to be
      educated in soft skills and that this will enhance their job performances in the
      clinical environment and improve the way in which they communicate with their
      clients.

PMID- 29041782
TI  - A model of collaboration between nursing education institutions in the North West
      Province of South Africa.
AB  - BACKGROUND: Professional nursing in South Africa is obtained through a 4-year
      diploma offered at nursing colleges, or a 4-year degree in universities, and the
      South African Nursing Council (SANC) registered both for professional nursing.
      New SANC legislation now requires a bachelor's degree for registration as
      professional nurse. OBJECTIVES: The aim of the study was to explore and describe
      perceptions of nurse educators and stakeholders to develop a model of
      collaboration for joint education and training of nursing professionals by
      colleges and universities through a bachelor's degree. METHOD: A mixed methods
      approach was used to explore perceptions of nurse educators utilising a
      questionnaire, and perceptions of other nurse training stakeholders through
      interviews, about a model of collaboration between the college and the
      university. RESULTS: Themes that emerged from the interviews included identifying
      collaboration goals, establishing a conducive environment, maximising exchange of
      resources, role clarification and perceived challenges. Quantitative results
      showed high agreement percentages (84.13%-100%) on most basic concepts and
      themes. A model of collaboration was developed indicating a framework, agents,
      recipients, procedure, dynamics, and terminus. CONCLUSION: A model of
      collaboration was acceptable to the majority of nurse education stakeholders.
      Other implications are that there was a need for the improvement of scholarship
      among nurse educators and clinical mentors, sharing rare skills, and addressing
      perceived challenges.

PMID- 29041784
TI  - Descriptive study of burnout, compassion fatigue and compassion satisfaction in
      undergraduate nursing students at a tertiary education institution in KwaZulu
      Natal.
AB  - BACKGROUND: Studies have investigated burnout and compassion fatigue among nurses
      and effects in the nursing profession. However, there are limited investigations
      of burnout and compassion fatigue among undergraduate nursing students in South
      Africa, as nursing students may experience distressful situations during their
      nursing education course, which may have an impact during their training and in
      their profession as they graduate. PURPOSE: The purpose of this descriptive study
      was to describe compassion satisfaction, compassion fatigue and burnout among
      undergraduate nursing students at a tertiary nursing institution. METHODS: A
      quantitative descriptive study was conducted to describe compassion satisfaction,
      compassion fatigue and burnout among undergraduate nursing students at a tertiary
      nursing institution in KwaZulu-Natal. Convenience sampling was used. RESULTS:
      Sixty-seven undergraduate students (26 third-year and 41 fourth-year nursing
      students) took the self-test Professional Quality of Life Scale (ProQOL). The
      study results indicate that undergraduate students experienced average levels of
      compassion fatigue, burnout and compassion satisfaction. CONCLUSION: As shown in
      the study, some of the undergraduate students are experiencing compassion fatigue
      and burnout, associated with relieving suffering of others. Therefore, knowledge
      of compassion fatigue and burnout and the coping strategies should be part of
      nursing training.

PMID- 29041783
TI  - The lived experiences and social support needs of first-time mothers at health
      care facilities in the City of Tshwane, South Africa.
AB  - BACKGROUND: Social support refers to the assistance people receive from others,
      and it is divided into four types of support. Given the increasing mortality and
      morbidity rates of mothers and neonates postpartum, this study intended to
      determine whether the social support needs of the first-time mothers were met
      after early discharge from health care facilities. OBJECTIVES: The objective of
      the study was to explore the lived experiences and social support needs of the
      first-time mothers after an early discharge from health care facilities in the
      City of Tshwane, Gauteng. METHOD: A qualitative explorative study was conducted
      to explore the lived experiences and social support needs of the first-time
      mothers. The population were first-time mothers who had a vaginal delivery and
      were discharged within 6-12 hours of delivery from health care facilities.
      Purposive sampling was performed and 14 semi-structured interviews were
      conducted, with those mothers who came for the prescribed three postnatal check
      ups at the three health care facilities identified according to maternity
      services provided. Saturation of data for the three health care facilities was
      reached at the 14th interview. Data analysis was performed using the hermeneutic
      interpretive approach. RESULTS: Almost all participants had completed grades 11
      or 12, but most were unemployed. The needs identified included the need for
      social support, lack of confidence, knowledge and skill to care for themselves
      and their newborn babies after early discharge. CONCLUSION: There is need to
      identify alternative types of social support for the first-time mothers, to
      ensure a normal adjustment to motherhood.

PMID- 29041785
TI  - Professional nurses' lived experiences regarding the performance management
      system in the Mopani district.
AB  - BACKGROUND: The purpose of the performance management system (PMS) is planning,
      monitoring, evaluation and development of employees to meet the organisational
      goals and objectives and transform of service delivery to excellence of the
      organisation. However, public services are deteriorating and implementation of
      PMS stimulated different views among professional nurses (PNs) in the Mopani
      district clinics, which warrants exploration and documentation of the findings.
      OBJECTIVE: The objective of this study was to explore and describe the PNs'
      perceptions towards PMS. METHODS: A qualitative, phenomenological research was
      conducted to explore and describe the nurses' lived experiences regarding PMS. A
      purposive sampling method was used. Data collection was done using focus group
      interviews. Three focus group discussion sessions were conducted, inclusive of
      six to nine participants in each session. RESULTS: Twenty-two PNs were
      interviewed. The findings revealed the following themes: PNs' uncertainty
      regarding the implementation of PMS, poor implementation of PMS and its process,
      lack of knowledge and understanding of PMS implementation and its process, and
      negative attitudes towards the implementation of PMS. CONCLUSION: PNs perceived
      PMS negatively. There is a need to improve leadership and management behaviour by
      enhancing productivity, job satisfaction and organisational commitment.
      Constructive feedback, training and capacity development, including
      standardisation and stabilisation of performance instrument, might improve the
      process.

PMID- 29041786
TI  - Census and vaccination coverage of owned dog populations in four resource-limited
      rural communities, Mpumalanga province, South Africa.
AB  - Dogs (Canis familiaris) are often free-roaming in sub-Saharan African countries.
      Rabies virus circulates in many of these populations and presents a public health
      issue. Mass vaccination of dog populations is the recommended method to decrease
      the number of dog and human rabies cases. We describe and compare four
      populations of dogs and their vaccination coverage in four different villages
      (Hluvukani, Athol, Utah and Dixie) in Bushbuckridge Municipality, Mpumalanga
      province, South Africa. Cross-sectional surveys were conducted in the villages of
      Athol, Utah and Dixie, while data from a Health and Demographic Surveillance
      System were used to describe the dog population in Hluvukani village. All
      households of the villages were visited to obtain information on the number, sex,
      age and rabies vaccination status of dogs. From May to October 2013, 2969
      households were visited in the four villages and 942 owned dogs were reported.
      The populations were all young and skewed towards males. No differences were
      observed in the sex and age distributions (puppies 0-3 months excluded) among the
      villages. Athol had a higher proportion of dog-owning households than Hluvukani
      and Utah. Vaccination coverages were all above the 20% - 40% threshold required
      for herd immunity to rabies (38% in Hluvukani, 51% in Athol, 65% in Dixie and 74%
      in Utah). For the preparation of vaccination campaigns, we recommend the use of
      the relatively stable dog:human ratio (between 1:12 and 1:16) to estimate the
      number of dogs per village in Bushbuckridge Municipality.

PMID- 29041787
TI  - A comparative analysis of mycotoxin contamination of supermarket and premium
      brand pelleted dog food in Durban, South Africa.
AB  - Dry pelleted dog food in the South African market is available via supermarkets,
      pet stores (standard brands [SBs]) and veterinary channels (premium brands
      [PBs]). For the purpose of this study, the supermarket channel included the
      cheaper quality foods and PBs were sold via the veterinary channel (n = 20).
      These feeds were analysed for four main mycotoxins (aflatoxins [AF], fumonisin
      [FB], ochratoxin A [OTA] and zearalenone [ZEA]) using standard welldescribed
      extraction, characterisation and quantitation processes. Irrespective of the
      brand or marketing channel, all foods were contaminated with fungi (mainly
      Aspergillus flavus, Aspergillus fumigatus and Aspergillus parasiticus) and
      mycotoxins (most prevalent being aflatoxins and fumonisins). This was observed in
      all 20 samples irrespective of the marketing channel or perceived quality. Also,
      many samples within each marketing channel failed the 10 ppb limit for aflatoxin
      set by regulations in South Africa. Although fumonisin was detected in all
      samples, a single sample failed the Food and Drug Administration (FDA) limit of
      100 ppb. Both OTA and ZEA were found at low concentrations and were absent in
      some samples. This study suggested that higher priced dog food does not ensure
      superior quality or that it is free from contamination with fungi or mycotoxins.
      However, analysis of the more expensive PBs did reveal contamination
      concentrations lower than those of the SBs.

PMID- 29041788
TI  - Use of <i>Brucella abortus</i> species specific polymerase chain reaction assay
      for the diagnosis of bovine brucellosis.
AB  - Serology is primarily used in the diagnosis of bovine brucellosis. Bacterial
      culture and isolation is the gold standard in diagnosing brucellosis but, like
      serology, it does not offer complete (100%) diagnostic sensitivity and
      specificity. Polymerase chain reaction (PCR) has been suggested to offer better
      specificity and sensitivity. In this study, we evaluated the performance of
      Brucella abortus species specific (BaSS) PCR directly from different samples in
      the diagnosis of bovine brucellosis in naturally infected cattle in KwaZulu-Natal
      province of South Africa with known infectious status from culture. The BaSS PCR
      had a low diagnostic sensitivity (DSe) of 70%, but was able to identify vaccine
      strains using abomasal fluid from aborted foetuses and detect Brucella DNA from
      decomposing samples. The best sample for the BaSS PCR was abomasal fluid.

PMID- 29041789
TI  - Epidemiological studies based on multi-locus sequence typing genotype of
      methicillin susceptible <i>Staphylococcus aureus</i> isolated from camel's milk.
AB  - One hundred milk samples were collected from camel's milk for the isolation of
      Staphylococcus aureus. Thirty-one isolates were S. aureus, 45 were other forms of
      staphylococci and 24 represented other bacteria. Five isolates from S. aureus
      were methicillin resistant S. aureus (MRSA) and 26 samples were methicillin
      susceptible S. aureus (MSSA). The whole genome sequence of S. aureus was
      annotated and visualised by rapid annotation using subsystem technology (RAST)
      which is a fully-automated service for annotating complete or nearly complete
      bacterial genomes. Four isolates from MSSA strains were subjected to multi-locus
      sequence typing (MLST). Three multilocus sequences types or sequence types
      (MLST/ST) were found, namely ST15, ST1153 and ST130. The phylogenetic analysis of
      the concatenated sequences of the seven genes forming the MLST profile of S.
      aureus classification revealed a high degree of similarity and close relationship
      between the ST15 and ST1153 while the third ST (ST130) was located in a different
      cluster.

PMID- 29041790
TI  - A retrospective study of anthrax on the Ghaap Plateau, Northern Cape province of
      South Africa, with special reference to the 2007-2008 outbreaks.
AB  - Anthrax is a zoonotic disease caused by the gram-positive, endospore-forming and
      soil-borne bacterium Bacillus anthracis. When in spore form, the organism can
      survive in dormancy in the environment for decades. It is a controlled disease of
      livestock and wild ungulates in South Africa. In South Africa, the two enzootic
      regions are the Kruger National Park and the Ghaap Plateau in the Northern Cape
      province. Farms on the Plateau span thousands of hectares comprising of wildlife 
      livestock mixed use farming. In 2007-2008, anthrax outbreaks in the province led
      to government officials intervening to aid farmers with control measures aimed at
      preventing further losses. Because of the ability of the organism to persist in
      the environment for prolonged periods, an environmental risk or isolation survey
      was carried out in 2012 to determine the efficacy of control measures employed
      during the 2007-2008, anthrax outbreaks. No B. anthracis could be isolated from
      the old carcass sites, even when bone fragments from the carcasses were still
      clearly evident. This is an indication that the control measures and protocols
      were apparently successful in stemming the continuity of spore deposits at
      previously positive carcass sites.

PMID- 29041791
TI  - Public awareness of audiology, hearing and hearing health in the Limpopo
      Province, South Africa.
AB  - BACKGROUND: The burden of hearing loss is on the increase, especially in low
      income countries such as South Africa. The need for urgent action to prevent ear
      and hearing problems is a priority, especially as in many cases permanent hearing
      loss is preventable. In South Africa, as in other developing countries, there is
      a limited number of hearing health professionals and audiological resources. The
      lack of hearing health services may impact the general public's awareness of
      hearing and hearing health. Limited information is available on the South African
      public's knowledge of audiologists and the services they provide, especially in
      underserved rural communities. AIM: The aim of this study was to describe
      individuals' awareness of the audiology profession, hearing and hearing loss, and
      hearing health in a rural area of the Limpopo Province. METHOD: A cross-sectional
      survey design was employed for the purpose of this study. Using a random sampling
      strategy, 297 households in four rural villages were selected and a selfdeveloped
      questionnaire was administered to one individual (18 years and older) per
      household. The questionnaire consisted of 23 questions targeting awareness of the
      audiology profession, as well as knowledge of hearing, hearing loss and hearing
      health. RESULTS: Only 14% of participants were aware of the audiology profession,
      indicating that individuals living in rural communities are not aware of the role
      of audiologists and the services they provide. Doctors and nurses were identified
      by participants as the individuals who assist them with hearing-related problems.
      Although most participants (87%) acknowledged that it is very important to
      undergo a hearing test, only 5% have previously visited an audiologist. Most
      participants were aware that ear infections and excessive noise exposure can
      cause hearing loss. The majority also believed that ears must be kept clean at
      all times and used cotton buds to maintain ear hygiene. CONCLUSION: There is a
      general lack of public awareness of audiologists and the services they offer.
      This study highlighted the need for the National Department of Health in
      collaboration with professional associations and hearing health professionals to
      develop and implement effective strategies to increase the South African public's
      awareness of the profession and the services they provide. South African
      universities can also play a significant role in teaching students to develop
      context-relevant strategies to increase awareness of the profession.

PMID- 29041792
TI  - The Besrour Papers: Seeking evidence for family medicine.
AB  - not available.

PMID- 29041793
TI  - Twenty years of Primafamed Network in Africa: Looking back at the future.
AB  - not available.

PMID- 29041794
TI  - The views of key stakeholders in Zimbabwe on the introduction of postgraduate
      family medicine training: A qualitative study.
AB  - BACKGROUND: Strengthening primary health care (PHC) is a priority for all
      effective health systems, and family physicians are seen as a key member of the
      PHC team. Zimbabwe has joined a number of African countries that are seriously
      considering the introduction of postgraduate family medicine training.
      Implementation of training, however, has not yet happened. AIM: To explore the
      views of key stakeholders on the introduction of postgraduate family medicine
      training. SETTING: Key academic, governmental and professional stakeholders in
      Zimbabwean health and higher education systems. METHOD: Twelve semi-structured
      interviews were conducted with purposively selected key stakeholders. Data were
      recorded, transcribed and analysed using the framework method. RESULTS:
      Anticipated benefits: More effective functioning of PHC and district health
      services with reduced referrals, improved access to more comprehensive services
      and improved clinical outcomes. Opportunities: International trend towards family
      medicine training, government support, availability of a small group of local
      trainers, need to revise PHC policy. Anticipated barriers: Family medicine is
      unattractive as a career choice because it is largely unknown to newly qualified
      doctors and may not be recognised in private sector. There is concern that
      advocacy is mainly coming from the private sector. Threats: Economic conditions,
      poor remuneration, lack of funding for resources and new initiatives, resistance
      from other specialists in private sector. CONCLUSION: Stakeholders anticipated
      significant benefits from the introduction of family medicine training and
      identified a number of opportunities that support this, but also recognised the
      existence of major barriers and threats to successful implementation.

PMID- 29041795
TI  - Knowledge of type 2 diabetic patients about their condition in Kimpese Hospital
      diabetic clinic, Democratic Republic of the Congo.
AB  - BACKGROUND: Diabetes mellitus is a worldwide increasing health problem of which
      type 2 diabetes is the most prevalent. Previously considered as a problem of
      industrialised countries, diabetes is currently a huge concern in developing
      countries and the Democratic Republic of the Congo (DRC) is one of the sub
      Saharan countries with a high prevalence rate of diabetes. Deficit of knowledge
      has already been shown to be one of the barriers preventing diabetic patients
      from controlling their disease. OBJECTIVES: This study aimed to assess the
      knowledge of type 2 diabetic patients seen at the Institut Medical Evangelique
      (IME) Kimpese Hospital diabetic clinic, DRC, and the factors associated with
      their knowledge. METHODS: A cross-sectional study involving 184 respondents was
      conducted at the diabetic clinic of the IME Kimpese Hospital, DRC. We
      administered a pre-tested questionnaire. Out of a total of 10, scores of < 5, 5
      to < 7, and >= 7 were classified as 'poor knowledge', 'moderate knowledge' and
      'good knowledge', respectively, according to expert consensus. All statistical
      tests were performed using p < 0.05 as the level of statistical significance.
      RESULTS: The mean age of respondents was 57.5 years (s.d. +/- 1.4, ranging from
      40 to 83 years), with 56% being male. The mean diabetes knowledge score was poor:
      3.2 out of a total of 10 (s.d. +/- 1.7), with the range between 0.2 and 7.7. The
      majority of respondents (72.3%) had poor general knowledge about diabetes
      mellitus. Respondents also scored poorly in areas of the causes (35.6%), risk
      factors (39.3%), clinical features (34.9%), complications (20.5%) and management
      (42.4%) of diabetes mellitus. Using the student t-test analysis, it was found
      that age (p = 0.001), gender (p = 0.002), educational level (p = 0.007) and
      duration of disease (p = 0.032) were significantly associated with poor knowledge
      of diabetes mellitus. CONCLUSIONS: Knowledge of diabetes mellitus among type 2
      diabetic patients seen at our setting was poor. Areas of deficiency and factors
      associated with knowledge of diabetes were identified. Our findings suggest the
      need for a health education intervention programme for our diabetic patients.

PMID- 29041796
TI  - Prevalence of eye pathology in a group of diabetic patients at National District
      Hospital Outpatient Department in Bloemfontein, South Africa.
AB  - BACKGROUND: Diabetic retinopathy is the third most common cause of blindness
      after cataracts and glaucoma in South Africa. Primary healthcare interventions
      providing eye care services play an important role in preventing complications.
      AIM: To determine the prevalence of eye pathology in a group of diabetic patients
      at National District Hospital by screening for diabetes-associated ocular
      pathology. SETTING: Outpatients Department run by Department of Family Medicine
      at National District Hospital in Bloemfontein from June to July 2014. METHODS:
      Interviews were used to collect information regarding diabetic patients' history
      of diabetes mellitus and if and when previous diabetic retinopathy screening was
      performed. Visual acuity was assessed, intra-ocular pressure measured and a non
      mydriatic digital fundus camera used to screen for retinal pathology. RESULTS:
      During the last year, only 4.5% of patients had their vision checked with a
      Snellen chart, and 16.5% were examined with an ophthalmoscope. Since diagnosis of
      diabetes, only 15.5% of patients were referred to an ophthalmologist. Patient
      referral was needed for 87 (42.9%) cases for refractive disorders, 37 (18.2%) for
      suspected glaucoma, 30 (14.8%) for cataracts, and 22 (10.8%) for diabetic
      retinopathy. CONCLUSION: This study confirms that glaucoma, cataracts and
      diabetic retinopathy are prevalent eye conditions among diabetic patients.
      Offering eye screening at primary healthcare level may contribute to early
      detection of eye pathology and timeous referral for sight-saving treatment.

PMID- 29041797
TI  - Geographical distribution and profile of medical doctors in public sector
      hospitals of the Limpopo Province, South Africa.
AB  - BACKGROUND: The shortage and unequal distribution of medical doctors in low- and
      middle-income countries continues to be a public health concern. OBJECTIVE: To
      establish the geographical distribution and demographic profile of medical
      doctors in public sector hospitals of the Limpopo Province, South Africa. METHOD:
      The PERSAL system was used to obtain information on the number of medical doctors
      employed in public sector hospitals of the Limpopo Province. Data were exported
      from PERSAL's database and then analysed using STATA version 9.0. RESULT: The
      mean age of the 887 medical doctors was 40.1 +/- 11.2 years (range 24-79 years).
      Sixty per cent of the doctors were male, 66% were aged <= 45 years and 84% were
      African. Most of the doctors (86%) were medical officers, of which 55% had < 5
      years working experience. Overall, the doctor-to-population ratio for the five
      districts in the province was 16.4/100 000, with Capricorn (33.7/100 000) and
      Waterberg (20.2/100 000) recording the highest ratios. A large proportion (43%)
      of medical officers are employed in the Capricorn District, of which 71% were
      practising at the tertiary hospital. CONCLUSION: This study demonstrated a
      shortage and maldistribution of medical doctors in the public sector hospitals of
      the Limpopo Province. This has a potentially negative effect on the delivery of
      an appropriate and efficient healthcare service to the population and requires
      urgent attention.

PMID- 29041798
TI  - Community perceptions of mental illness in rural Uganda: An analysis of existing
      challenges facing the Bwindi Mental Health Programme.
AB  - OBJECTIVES: To assess community perceptions of mental illness in the Bwindi
      Community Hospital (BCH) catchment area: to recognise beliefs about the causes
      and the treatments for mental illness. To provide community data to staff at BCH
      as they work to develop more effective community mental health programmes.
      BACKGROUND: A shortage of mental health providers in Uganda has prompted research
      into community-based task-sharing models for the provision of mental health
      services in underserved communities. METHODS: Six focus group discussions, with a
      total of 54 community members (50% male, n = 27; mean age + s.d. [39.9 + 10.9
      years]) from the BCH catchment area, were conducted to assess community member
      and stakeholder perceptions of mental illness and belief in the feasibility of
      community-based programming. Qualitative study of data through thematic analysis
      was conducted to assess the presence of commonly occurring perceptions. RESULTS:
      Qualitative thematic analysis revealed two major themes: (1) belief that any
      given patient's metal illness results from either an intrinsic or an extrinsic
      cause and (2) belief in a need to determine treatment of mental illness based on
      the believed cause. CONCLUSION: As BCH designs community-based mental health
      services, our findings provide support for the need for further education of
      community members and training of community health workers to address and
      integrate the above-stated beliefs regarding mental illness.

PMID- 29041799
TI  - The value of the WIRHE Scholarship Programme in training health professionals for
      rural areas: Views of participants.
AB  - INTRODUCTION: Rural hospitals in South Africa, as elsewhere, face enduring
      shortages of, and challenges in attracting and retaining, suitably qualified
      staff. The Wits Initiative for Rural Health Education (WIRHE), based at the
      University of the Witwatersrand but covering three universities, is a rural
      scholarship programme established to find local solutions to these challenges in
      the North West and Mpumalanga provinces. The purpose of this evaluation was to
      ascertain whether the WIRHE project was achieving its objectives. METHODS: This
      article draws from an evaluation commissioned by the Swiss-South African
      Cooperative Initiative, a major funder of the programme when WIRHE was launched
      in 2003. Qualitative interviews were conducted either as face-to-face meetings or
      telephonically with 21 WIRHE students and graduates. Content analysis was
      undertaken to identify common themes. RESULTS: There was a consistency in the
      findings as the students and graduates reported similar experiences. Many of the
      participants were overwhelmed by their initial challenges of having to adapt to a
      different language, an institutional culture and resources that they previously
      did not have access to. The participants acknowledged the role of WIRHE staff in
      facilitating the transition from home to university and, in particular, the value
      of the financial and academic support. The geographic distance to Wits presented
      a challenge for the Pretoria- and Sefako Makgatho-based students. The holiday
      work affirmed clinical advantages for WIRHE students and heightened students'
      interest in becoming healthcare workers. CONCLUSION: WIRHE's key success factors
      are the financial, academic and emotional support offered to students. WIRHE
      achieved its objectives based on a principled strategic approach and an
      understanding that students from rural backgrounds are more likely to return to
      rural areas. The study supports the value of structured support programmes for
      students of rural origin as they pursue their studies.

PMID- 29041800
TI  - An exploration of the knowledge, attitudes and beliefs of Xhosa men concerning
      traditional circumcision.
AB  - BACKGROUND: The practice of traditional circumcision is associated with
      considerable morbidity and mortality, yet there is a paucity of literature that
      provides an understanding of the cultural values that influence men to choose
      traditional rather than medical circumcision.The aim of this study was to better
      understand the culture surrounding traditional circumcision, with a view to
      addressing morbidity and mortality rates associated with the Xhosa male
      initiation rituals.We explored Xhosa men's perceptions regarding the need for the
      risks and the social pressure to undergo traditional circumcision, the impact of
      non-initiation or failed initiation and the perceived barriers to obtaining
      medical help for the complications of traditional circumcisions. METHODS:
      Individual in-depth interviews were conducted with 10 purposively sampled
      teenagers and adult men. The interviews were recorded, translated, transcribed
      and analysed using the framework method. RESULTS: Traditional circumcision was
      seen as essential to Xhosa culture. Participants rationalised many reasons for
      participating, including personal growth and development, family and peer
      pressure, independence and knowledge gained, a connection with ancestors and
      initiation into manhood. Despite publicity of the dangers of traditional
      circumcision and the hardships they have to endure, most young men still saw this
      process as necessary and worthwhile. CONCLUSION: Traditional initiation and
      circumcision are here to stay. The majority of boys still trust the elders and
      supernatural processes to guide them. However, some participants welcomed
      government initiatives to reduce human error causing unnecessary death and
      suffering. Current systems to prevent morbidity and mortality are insufficient
      and should be prioritised.

PMID- 29041801
TI  - Perceptions of clients on awareness and the geographical location of a South
      African university sexual health clinic.
AB  - BACKGROUND: The Campus Health Service at Stellenbosch University has a sub
      division, a sexual health clinic, which provides sexual health services. The
      clients of the sexual health clinic consist of staff members and students. AIM:
      This article reports on the perceptions of clients that relate to awareness and
      the geographical location of the clinic. SETTING: The Campus Health Service at
      Stellenbosch University's main campus. METHOD: A descriptive qualitative approach
      was applied utilising in-depth interviews. A sample of n = 15 was drawn through
      purposive sampling and data saturation was achieved with the sample. RESULTS: The
      following themes emerged from the data: location of the clinic, awareness of
      sexual health services and marketing and advertising. CONCLUSION: The findings of
      the study revealed that accessibility of the clinic is influenced by the
      geographical location of the clinic and that marketing and awareness of services
      require attention.

PMID- 29041803
TI  - [Articles of the Hungarian Medical Journal from May, 2006].

PMID- 29041804
TI  - [Articles of the Hungarian Medical Journal from October, 2006].

PMID- 29041802
TI  - Decentralised training for medical students: Towards a South African consensus.
AB  - INTRODUCTION: Health professions training institutions are challenged to produce
      greater numbers of graduates who are more relevantly trained to provide quality
      healthcare. Decentralised training offers opportunities to address these
      quantity, quality and relevance factors. We wanted to draw together existing
      expertise in decentralised training for the benefit of all health professionals
      to develop a model for decentralised training for health professions students.
      METHOD: An expert panel workshop was held in October 2015 initiating a process to
      develop a model for decentralised training in South Africa. Presentations on the
      status quo in decentralised training at all nine medical schools in South Africa
      were made and 33 delegates engaged in discussing potential models for
      decentralised training. RESULTS: Five factors were found to be crucial for the
      success of decentralised training, namely the availability of information and
      communication technology, longitudinal continuous rotations, a focus on primary
      care, the alignment of medical schools' mission with decentralised training and
      responsiveness to student needs. CONCLUSION: The workshop concluded that training
      institutions should continue to work together towards formulating decentralised
      training models and that the involvement of all health professions should be
      ensured. A tripartite approach between the universities, the Department of Health
      and the relevant local communities is important in decentralised training.
      Lastly, curricula should place more emphasis on how students learn rather than
      how they are taught.

PMID- 29041805
TI  - [Articles of the Hungarian Medical Journal from July, 2006].

PMID- 29041806
TI  - [Articles of the Hungarian Medical Journal from September, 2006].

PMID- 29041807
TI  - [Articles of the Hungarian Medical Journal from January, 2006].

PMID- 29041808
TI  - [Articles of the Hungarian Medical Journal from June, 2006].

PMID- 29041810
TI  - [Articles of the Hungarian Medical Journal from April, 2006].

PMID- 29041811
TI  - Consecutive loss of two benzyl radicals from the [M + Na]+ adduct ions of
      pyrogallol tribenzyl ether and its derivatives.
AB  - The electrospray ionization-collision-induced dissociation mass spectra of nine
      pyrogallol tribenzyl ethers, 2-10, and a catechol dibenzyl ether, 11, that bear
      various functional groups or larger structural extensions have been studied with
      respect to the occurrence of a highly characteristic consecutive loss of two
      benzyl radicals from the sodiated molecular ions, [M + Na]+. It is shown that
      this specific fragmentation reaction strongly dominates other fragmentation
      routes, such as loss of carbon monoxide, formaldehyde and water. In addition,
      elimination of benzaldehyde occurs as a minor fragmentation channel in most
      cases. In contrast to these aryl-benzyl ethers, the consecutive two-fold loss of
      C7H7* is suppressed in the [M + Na]+ ions of dibenzyl ethers derived from
      multiply benzylated gallocatechin and catechin, where the elimination of benzyl
      alcohol prevails the primary fragmentation almost completely. The secondary
      fragmentation of the [M + Na]+ ions, which also comprises the two-fold loss of
      C7H7*, as well as a remarkable primary fragmentation of a flavene-based congener
      leading to particularly stable sodium-free chromylium product ions is also
      presented. ? Deceased.

PMID- 29041812
TI  - [Articles of the Hungarian Medical Journal from December, 2006].

PMID- 29041813
TI  - Regulatory science requirements of labeling of genetically modified food.
AB  - This paper provides an overview of the evolution of food labeling in the USA. It
      briefly describes the three phases of agricultural development consisting of
      naturally occurring, cross-bred, and genetically engineered, edited or modified
      crops, otherwise known as Genetically Modified Organisms (GMO). It uses the Best
      Available Regulatory Science (BARS) and Metrics for Evaluation of Regulatory
      Science Claims (MERSC) to evaluate the scientific validity of claims applicable
      to GMO and the Best Available Public Information (BAPI) to evaluate the
      pronouncements by public media and others. Subsequently claims on health risk,
      ecological risk, consumer choice, and corporate greed are evaluated based on
      BARS/MERSC and BAPI. The paper concludes by suggesting that labeling of food
      containing GMO should consider the consumer's choice, such as the food used by
      those who desire kosher and halal food. Furthermore, the consumer choice is
      already met by the exclusion of GMO in organic food.

PMID- 29041814
TI  - [Articles of the Hungarian Medical Journal from November, 2006].

PMID- 29041815
TI  - [Articles of the Hungarian Medical Journal from August, 2006].

PMID- 29041816
TI  - Enhanced susceptibility to cortical spreading depression in two types of Na+,K+
      ATPase alpha2 subunit-deficient mice as a model of familial hemiplegic migraine
      2.
AB  - Background Patients with familial hemiplegic migraine type 2 (FHM2) have a
      mutated ATP1A2 gene (encoding Na+,K+-ATPase alpha2 subunit) and show prolonged
      migraine aura. Cortical spreading depression (CSD), which involves mass
      depolarization of neurons and astrocytes that propagates slowly through the gray
      matter, is profoundly related to aura. Methods In two types of Atp1a2-defective
      heterozygous mice, Atp1a2tm1Kwk (C-KO) and Atp1a2tm2Kwk (N-KO), the sensitivity
      and responsiveness to CSD were examined under urethane anesthesia. Results In
      both cases, heterozygotes exhibited a low threshold for induction of CSD, faster
      propagation rate, slower recovery from DC deflection, and profound suppression of
      the electroencephalogram, compared to wild-type mice. A high dose of KCl elicited
      repeated CSDs for a longer period, with a tendency for a greater frequency of CSD
      occurrence in heterozygotes. The difference of every endpoint was slightly
      greater in N-KO than C-KO. Change of regional cerebral blood flow in response to
      CSD showed no significant difference. Conclusion Heterozygotes of Atp1a2
      defective mice simulating FHM2 demonstrated high susceptibility to CSD rather
      than cortical vasoreactivity, and these effects may differ depending upon the
      knockout strategy for the gene disruption. These results suggest that patients
      with FHM2 may exhibit high susceptibility to CSD, resulting in migraine.

PMID- 29041817
TI  - Supratentorial lesions contribute to trigeminal neuralgia in multiple sclerosis.
AB  - Background It has been proposed that multiple sclerosis lesions afflicting the
      pontine trigeminal afferents contribute to trigeminal neuralgia in multiple
      sclerosis. So far, there are no imaging studies that have evaluated interactions
      between supratentorial lesions and trigeminal neuralgia in multiple sclerosis
      patients. Methods We conducted a retrospective study and sought multiple
      sclerosis patients with trigeminal neuralgia and controls in a local database.
      Multiple sclerosis lesions were manually outlined and transformed into
      stereotaxic space. We determined the lesion overlap and performed a voxel-wise
      subtraction analysis. Secondly, we conducted a voxel-wise non-parametric analysis
      using the Liebermeister test. Results From 12,210 multiple sclerosis patient
      records screened, we identified 41 patients with trigeminal neuralgia. The voxel
      wise subtraction analysis yielded associations between trigeminal neuralgia and
      multiple sclerosis lesions in the pontine trigeminal afferents, as well as larger
      supratentorial lesion clusters in the contralateral insula and hippocampus. The
      non-parametric statistical analysis using the Liebermeister test yielded similar
      areas to be associated with multiple sclerosis-related trigeminal neuralgia.
      Conclusions Our study confirms previous data on associations between multiple
      sclerosis-related trigeminal neuralgia and pontine lesions, and showed for the
      first time an association with lesions in the insular region, a region involved
      in pain processing and endogenous pain modulation.

PMID- 29041818
TI  - A content analysis of peripheral arterial disease patient-reported outcome
      measures using the International Classification of Functioning, Disability and
      Health.
AB  - BACKGROUND: The purpose of this study was to link, classify and describe the
      content of peripheral arterial disease (PAD)-specific patient-reported outcome
      measures using the International Classification of Functioning. The results were
      then analyzed to determine if these assessments provide clinicians and
      researchers with a comprehensive understanding of the lived experience of
      patients with PAD. METHODS: Each meaningful concept in identified PAD assessments
      was linked to the International Classification of Functioning, Disability and
      Health to determine included and excluded content areas. An overall perspective
      was assigned to each assessment item. Inter-rater reliability was established
      using a kappa statistic. RESULTS: The body functions component is most frequently
      addressed overall followed by the activities and participation component.
      International Classification of Functioning chapter and category distribution
      vary greatly between assessments and no assessment comprehensively examines
      community participation and relationships. The majority of the assessment items
      are of the health status-disability and quality of life perspectives.
      CONCLUSIONS: The results of this study suggest the need for the development of a
      comprehensive PAD assessment that includes a more even distribution of
      International Classification of Functioning topics and subtopics. A more
      comprehensive assessment would better capture the lived experience of this
      patient population. Implications for Rehabilitation A better understanding of the
      data collected using the current peripheral arterial disease-specific patient
      reported outcome measures may contribute to the development of more comprehensive
      assessment tools that will ultimately lead to improved patient care. This study
      contributes to the preliminary foundation for the development of a peripheral
      arterial disease International Classification of Functioning, Disability and
      Health Core Set. Clinicians and researchers interested in using peripheral
      arterial disease-specific patient-reported outcome measures for clinical and
      research purposes can better understand what topics are included and excluded in
      the collection and what perspectives are addressed.

PMID- 29041819
TI  - Subjective health complaints and illness perception amongst adults with Joint
      Hypermobility Syndrome/Ehlers-Danlos Syndrome-HypermobilityType - a cross
      sectional study.
AB  - OBJECTIVE: To investigate the prevalence and severity of subjective health
      complaints and describe illness perception in a population of Joint Hypermobility
      Syndrome or Ehlers-Danlos Syndrome-Hypermobile Type. METHOD: This study was a
      postal survey with a questionnaire battery on demographic data, subjective health
      complaints inventory, and illness perception. A total of 110 individuals
      diagnosed with Joint Hypermobility Syndrome or Ehlers-Danlos Syndrome-Hypermobile
      Type from two specialized hospitals in Norway were offered participation.
      Further, 140 gender- and age-matched healthy controls from statistics Norway
      representing the general population were sent the questionnaire for reference.
      RESULTS: Overall response rate was 30.4% (n = 76), with 44.5% (n = 49) in Joint
      Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobile Type and 19.3% (n = 27)
      in controls. Subjective health complaints were significantly higher in Joint
      Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobile Type - than in the
      controls (32.06 vs. 11.08; p < 0.001). Further the brief illness perception
      questionnaire indicated that the adults with Joint Hypermobility Syndrome/Ehlers
      Danlos Syndrome-Hypermobile Type had low understanding of their illness and
      symptoms (understanding, mean: 3.93, SD 2.88), and reported to have moderate
      personal and treatment control over their illness. CONCLUSION: Adults with Joint
      Hypermobility Syndrome/Ehlers-Danlos Syndrome-Hypermobile Type reported higher
      frequency and severity of subjective health complaints than the matched controls
      from the general adult population in Norway. Furthermore, Joint Hypermobility
      Syndrome/Ehlers-Danlos Syndrome-Hypermobile Type reported low understanding of
      their illness and associated symptoms, and moderate belief that their illness can
      be kept under control through self-management or treatment. This may indicate one
      of the reasons why prognosis for these patients is poor. Implications for
      rehabilitation Awareness of the complexity of the subjective health complaints
      and inquiry into illness perception could contribute with valuable information
      about these patients' perceptions of their condition. Such information could in
      its turn be of value for clinicians as they work towards facilitating a more
      holistic treatment approach, for example patient education and cognitive
      behavioural therapy.

PMID- 29041821
TI  - Gender matters in the transition to employment for young adults with physical
      disabilities.
AB  - PURPOSE: The purpose of this study was to explore the role of gender in the
      transition to employment for young adults with physical disabilities. METHODS:
      This study drew on in-depth interviews with a purposive sample of 33 participants
      (23 youth and 10 clinicians). The youth in our sample included 13 females (mean
      age 22.9) and 10 males (mean age 21.3) who had various types of physical
      disabilities. The person-environment-occupation (PEO) model informed our
      analysis. RESULTS: Our research showed several similarities and some differences
      between young males and females with physical disabilities as they transition to
      employment and adulthood at the person, environment, and occupational level. At
      the person level, issues included managing their condition, self-advocacy, and
      willingness to ask for help. At the environment level, themes focused on parental
      and social support, accommodations, stigma and discrimination, and transportation
      challenges. Finally, in the occupation component of the PEO model, we found that
      males and females with disabilities had different levels of engagement in
      employment. Although most clinicians commented on gender differences, many
      reported that they did not tailor their clinical practice accordingly.
      CONCLUSIONS: Gender sensitive vocational approaches are needed for youth with
      disabilities as they transition to employment. Implications for rehabilitation
      Clinicians, educators, and parents should encourage independence and self
      advocacy skills among youth so that they are prepared to ask for accommodations
      that they need to succeed in a work environment. Clinicians and educators should
      present a variety of career and job options to youth, including science,
      technology, engineering, and math disciplines, an area where youth with
      disabilities, particularly females, are under-represented. Males may feel less
      able to self-advocate and seek support and may need additional assistance from
      clinicians, educators, and parents. Clinicians should tailor their vocational
      rehabilitation practices to the gender-specific needs of youth with disabilities.
      Clinicians and parents should ensure that both males and females have the
      resources and supports they need to be successful in their transition to
      employment.

PMID- 29041820
TI  - Applying the ICF linking rules to compare population-based data from different
      sources: an exemplary analysis of tools used to collect information on
      disability.
AB  - BACKGROUND: Data on disability are regularly collected by different institutions
      or ministries using specific tools for different purposes, for instance to
      estimate the prevalence of disability or eligibility of specific populations for
      social benefits. The interoperability of disability data collected in countries
      is essential for policy making and to monitor the implementation of the
      Convention on the Rights of Persons with Disabilities. The first objective of
      this paper is to map and compare tools that collect data on disability for
      different purposes, more specifically the Brazilian National Health Survey and
      the Brazilian Functioning Index to the World Health Organization (WHO) and the
      World Bank Model Disability Survey (MDS), currently recommended as a standard
      tool for disability measurement. The second objective is to demonstrate the
      usefulness and value of the International Classification of Functioning,
      Disability and Health Linking Rules to map and compare population-based surveys
      and other content-related tools collecting data on disability, even when these
      have already been developed based on the International Classification of
      Functioning, Disability and Health. METHODS: Disability information collected
      with the three different tools was mapped and compared using the International
      Classification of Functioning, Disability and Health Linking Rules. RESULTS:
      Although the disability module in the Brazilian National Health Survey is
      fundamentally different from the MDS, the mapping disclosed that several modules
      of the Brazilian National Health Survey already cover many aspects necessary to
      estimate prevalence and understand disability as currently recommended by the WHO
      and the World Bank. The Brazilian Functioning Index and the MDS are both based on
      the International Classification of Functioning, Disability and Health and are
      very similar in the approach and content of their questions on functioning.
      Specific information on environmental factors is essential to identify needs and
      barriers, as well as to devise procedures to reduce injustice and inequalities.
      This information is still not targeted broadly enough in both the Brazilian
      National Health Survey and the Brazilian Functioning Index. CONCLUSIONS: Overall,
      this mapping exercise showed that applying the International Classification of
      Functioning, Disability and Health linking rules to population-based data coming
      from different sources provides researchers and stakeholders involved in decision
      making with standardized and straightforward information about overlaps and gaps.
      Implications for Rehabilitation Data on functioning and disability regularly
      collected with different purposes and by different institutions or ministries
      within a country can be compared using the International Classification of
      Functioning, Disability and Health as a reference framework and the International
      Classification of Functioning, Disability and Health linking rules. The recently
      published refinements of the International Classification of Functioning,
      Disability and Health Linking Rules go beyond the sole linking to International
      Classification of Functioning, Disability and Health categories and provide
      standardized procedures to document the perspective of linked questions or the
      categorization of response options. They are therefore useful to compared tools
      that have been developed based on the International Classification of
      Functioning, Disability and Health. The current disability module of the
      Brazilian Health Survey needs a revision to be suitable to collect data on
      disability that is Convention on the Rights of Persons with Disabilities conform
      and guarantees interoperability with disability data from other sources in
      Brazil, especially from disability assessment for social benefits and
      implementation of policies.

PMID- 29041822
TI  - When I do, I become someone: experiences of occupational performance in young
      adults with cerebral palsy.
AB  - PURPOSE: Persons with cerebral palsy, even if they have relatively good motor
      functions, have a lower level of independence and participation in everyday
      activities than persons of the same age without disabilities. However, there are
      few descriptions of how persons with cerebral palsy themselves perceive their
      performance of activities in everyday life. The aim of this study was to describe
      the perceptions that young adults with cerebral palsy have of occupational
      performance in everyday life. METHODS: This qualitative interview study includes
      10 participants with cerebral palsy classified with Manual Ability Classification
      System level I-II, aged 19-30 years. The data were analyzed using a
      phenomenographic approach. RESULTS: The interviews resulted in five categories:
      "Important to do"; "Demanding but can be facilitated"; "Excludes or includes";
      "Diminishes me or makes me grow"; and "Comes at a price". CONCLUSIONS: The young
      adults with cerebral palsy consider that, despite life being so demanding, it is
      extremely important to perform activities themselves and to feel included, as
      this enables personal growth. Hence, it is necessary to advance intervention
      methods based on personally important activities to enable individuals with
      cerebral palsy to find their own way to perform activities. Further research is
      needed to increase opportunities for individuals with cerebral palsy to perform
      everyday activities without too much fatigue and struggle. Implications for
      Rehabilitation For young adults with cerebral palsy it is extremely important to
      perform everyday activities independently; by DOING activities they form their
      identity. Intervention models aimed to enable persons with cerebral palsy to be
      involved and find their own way to perform everyday activities should be
      emphasized. Attention must be paid to how mental fatigue is manifested in persons
      with cerebral palsy. To build self-awareness and self-efficacy, individuals with
      cerebral palsy need information, early in life, about cerebral palsy and the
      multifaceted difficulties the disability might lead to.

PMID- 29041823
TI  - Therapists' cues influence lower limb muscle activation and kinematics during
      gait training in subacute stroke.
AB  - PURPOSE: Symmetrical gait is a key goal of rehabilitation post-stroke. Therapists
      employ techniques such as verbal instruction and haptic cues to increase
      activation of paretic muscles. We examined whether verbal or tactile cueing
      altered spatiotemporal gait parameters, kinematics and electromyography (EMG) of
      lower limb muscles on the more-affected side within a training session. MATERIALS
      AND METHODS: Patients (n = 10) were recruited from rehabilitation services (<9
      months post-stroke). Tactile (to the hip muscles) or verbal cues were provided on
      two testing days, 7-10 days apart (randomized order). Gait and angular kinematics
      were recorded using a Vicon motion capture system and muscle activation using
      EMG; at baseline (PRE), during the cue, directly afterwards without a cue (POST)
      and 20 min later without a cue (RETEST). RESULTS: Both verbal and tactile cueing
      significantly increased muscle activity in paretic muscles but with no immediate
      effect on step length asymmetry. Tactile cues, more than verbal, temporarily
      altered gait speed, cadence and time in double support. Verbal cues caused more
      robust increases in muscle activation of vastus lateralis at weight acceptance
      and medial gastrocnemius activity from toe off to midswing. CONCLUSIONS: Within a
      treatment session, tactile cues more effectively altered cadence and double
      support time while verbal cues more consistently increased vastus lateralis and
      medial gastrocnemius activity. The effectiveness of these methods in fostering
      motor relearning in the longer term is an important area for future research.
      Implications for Rehabilitation Therapist cueing alters muscle activity on
      hemiparetic side with no effects on symmetry. Tactile cues, more so than verbal
      cues, increase cadence and reduce time in double support. Verbal cues are more
      effective at increasing vastus lateralis and plantarflexor muscle activity.

PMID- 29041824
TI  - A new nanoemulsion formulation improves antileishmanial activity and reduces
      toxicity of amphotericin B.
AB  - This work aimed to optimise a new nanoemulsion (NE) formulation loaded with
      Amphotericin B (AmB) and to evaluate its in vivo antileishmanial activity and in
      vitro haemolytic toxicity. The influence of gradual increases in pressure, using
      a high-pressure homogeniser, was evaluated. The NE was characterised for droplet
      size, polydispersity index, zeta potential and encapsulation efficiency (EE). For
      antileishmanial activity studies, AmB-NE was administered intravenously in mice
      infected by Leishmania infantum chagasi, which causes Visceral Leishmaniasis
      (VL). When the NE was submitted to gradual increases in pressure, the PI values
      and droplet size decreased. The droplet size (~145 nm) was lower than that
      obtained in previous studies. The zeta potential was negative and the EE was
      almost 100%. The haemolytic toxicity, evaluated on human red blood cells, for AmB
      loaded NE was lower than that observed for the conventional AmB (C-AmB). C-AmB at
      2 mg/kg was very toxic. In contrast, administration of the AmB-loaded NE, at same
      dose, did not result in any sign of acute toxicity, promoting a significant
      reduction in parasite burden as compared to the C-AmB. These findings suggest
      that this new AmB-loaded NE constitutes an attractive alternative for the
      treatment of VL due to improved efficacy and lower toxicity.

PMID- 29041825
TI  - Cathepsin L deficiency results in reactive oxygen species (ROS) accumulation and
      vascular cells activation.
AB  - Recent evidence suggests a link between cathepsin L (CTSL) and vascular diseases.
      However, its contribution to reactive oxygen species (ROS) homeostasis in the
      vasculature remains unknown. p66shc is a redox enzyme implicated in mitochondrial
      ROS generation and translation of oxidative signals. In this study, we explored
      the relationship between CTSL and oxidative damage in vasculature and whether the
      oxidative damage is mediated by p66shc.Carotid arteries from aged mice (24 months
      old) showed a reduction in CTSL expression compared with young wild-type mice (4
      months old). Local knockdown of CTSL in carotid arteries of young mice by
      adenoviral vector encoding the short hairpin RNA targeting CTSL leading to
      premature vascular aging, as shown by mitochondrial disruption, increased beta
      galactosidase-positive cells, reduced telomerase activity, and up-regulation of
      p66shc. Knockdown of CTSL decreased the expression of mitochondrial oxidative
      phosphorylation (OXPHOS) complexes I, III, and IV, leading to increased
      mitochondrial ROS and hyperpolarization of the mitochondrial membrane in vitro.
      Furthermore, knockdown of CTSL also stimulated ROS production and senescence in
      vascular cells, accompanied by the up-regulation of p66shc.However, p66shc
      knockdown blunted the alteration in ROS production, and senescence in CTSL
      knockdown vascular cells. This study suggests that CTSL knockdown partially
      induces vascular cells damage via increased ROS production and up-regulation of
      p66shc.

PMID- 29041826
TI  - Use of acellular pertussis vaccines in the United States: can we do better?
AB  - INTRODUCTION: Despite robust vaccination schedules and high vaccination rates,
      many countries, including the U.S., have seen large pertussis outbreaks with a
      shift in recent years in the distribution of disease burden towards adolescents
      and young adults. Areas covered: This perspective covers problems related to the
      increased incidence of pertussis among adolescents. Because the Tdap vaccine only
      protects against pertussis for 1-2 years after vaccination, we propose a new
      strategy which aims to optimize the benefit of Tdap in adolescents. Expert
      commentary: Current pertussis vaccination schedules are based on age and have not
      been effective at protecting adolescents and teenagers from pertussis outbreaks.
      An alternative to the current practice would be to take advantage of the cyclical
      nature of pertussis outbreaks. Rather than immunizing children and adolescent
      solely based on age regardless of risk of pertussis at that moment, perhaps we
      should consider a 'timed' Tdap. The goal would be to administer Tdap to
      susceptible adolescents and young adults during periods when there is a greater
      risk of being exposed to pertussis. This approach would optimize the use of an
      effective, but short-lived vaccine by maximizing protection at the time of
      increased risk.

PMID- 29041827
TI  - Total dietary sugar consumption does not influence sleep or behaviour in
      Australian children.
AB  - This study aimed to compare sugar intake in Australian children with current
      guidelines and determine if total sugar consumption as a percentage of energy
      (sugar %E) exacerbates the relationship between sleep and behaviour. A sample of
      287 children aged 8-12 years (boys 48.8%, age: 10.7 +/- 1.3 years), and their
      parents/guardians completed a battery of questionnaires. Children completed a
      food frequency questionnaire, and parents completed demographic, sleep, and
      behaviour questionnaires. Average sugar intake was 134.9 +/- 71.7 g per day
      (sugar %E 26.0 +/- 7.0%), and only 55 (19%) participants did not exceed the
      recommended sugar intake limit. Correlations and logistical regressions indicated
      that sugar %E was not associated with sleep or behavioural domains (r range = 
      0.07-0.08; p range = .173-.979) nor contributed to the prediction of sleep
      behaviour problems (p range = .16-.80). Whilst a high proportion of children
      consumed above the recommended amount of daily total sugar, total sugar
      consumption was not related to behavioural or sleep problems, nor affected the
      relationship between these variables.

PMID- 29041828
TI  - Urine protein biomarkers for detection of cardiovascular disease and their use
      for the clinic.
AB  - INTRODUCTION: Cardiovascular disease (CVD) is the leading noncommunicable disease
      and main cause of death worldwide. Traditionally, blood has been the sample of
      choice for biomarker discovery, however, urine has roused great interest in
      recent years as a source of biomarkers. Sample collection is simple, non
      invasive, and there is the possibility of implementing minimal cost tests in
      primary care settings. Areas covered: In this review, we systematically searched
      PubMed for proteomic studies of CVD, with the criteria that urine was included as
      a biological sample. Based on these criteria, and after manual curation, 47
      research papers were included: 8 for coronary artery disease, 5 for angina, 15
      for myocardial infarction, 23 for heart failure, and 4 for cerebrovascular
      disease. Expert commentary: Urinary biomarkers of early, asymptomatic stages of
      the disease would have a great impact on CVD morbidity and mortality, as
      widespread screening could be implemented at a reduced cost, allowing high-risk
      individuals to be identified and treated in a timely manner. An approach
      involving multiple biomarkers is necessary, as a single biomarker is unlikely to
      be sensitive/specific enough. By assessing a range of peptides there is the
      potential to detect changes in many pathways involved in the pathogenesis of
      CVDs.

PMID- 29041829
TI  - Characteristics and outcome of severe preeclampsia/eclampsia concurrent with or
      complicated by acute pancreatitis: a report of five cases and literature review.
AB  - OBJECTIVE: The objective of this study is to determine the rate of acute
      pancreatitis in preeclampsia/eclampsia patients and describe the clinical
      manifestations, treatment characteristics and outcome of five cases of severe
      preeclampsia concurrent with or complicated by acute pancreatitis. METHODS: The
      clinical data of pregnant women with preexisting or gestational hypertension who
      sought medical care between January 2002 and December 2015 at the Pregnant Women
      Critical Care Unit of Chaoyang Hospital, Capital Medical University, Beijing,
      China were retrieved. The rate of acute pancreatitis in preeclampsia/eclampsia
      patients was calculated and patients with preeclampsia/eclampsia and acute
      pancreatitis were included for further analysis. RESULTS: Totally 1703 pregnant
      women who received medical care at our institution during the review period were
      diagnosed with hypertension. Four hundred and seven (23.9%) of them had severe
      preeclampsia. Five (1.2%, 5/407) women with severe preeclampsia developed acute
      pancreatitis. Their median age was 32 (range 25-35) years and the median duration
      of gestation was 32 (range 28-40) weeks. Mild acute pancreatitis occurred in
      three cases, and moderately severe and severe acute pancreatitis in one case
      each. Four patients underwent cesarean resection and one patient underwent
      vaginal delivery. Conservative therapy was undertaken. No patient received
      surgical intervention and cure was achieved in all patients. CONCLUSION: Acute
      pancreatitis may complicate severe preeclampsia/eclampsia or may be concurrent
      with severe preeclampsia/eclampsia, complicating and compromising the management
      of preeclampsia/eclampsia. Physicians should be alert for the presence of acute
      pancreatitis as prompt diagnosis and treatment, rapid termination of pregnancy
      and subsequent conservative management of pancreatitis could lead to a general
      favorable outcome.

PMID- 29041830
TI  - General outcomes and risk factors for minor and major amputations in Brazil.
AB  - Objectives Major and minor amputations are associated with significant rates of
      mortality. However, little is known about the impact of unplanned redo-amputation
      during the same hospitalization on outcomes. The objectives of this study were to
      identify the risk factors associated with in-hospital mortality after both major
      and minor amputations as well as the results of unplanned redo-amputation on
      outcome. Methods Retrospective study of 342 consecutive patients who were treated
      with lower extremity amputation in Brazil between January 2013 and October 2014.
      Results The in-hospital mortality rate was higher in major compared to minor
      amputation (25.6% vs. 4.1%; p < 0.0001). Whereas chronic kidney disease, chronic
      obstructive pulmonary disease, and planned staged amputation predicted in
      hospital mortality after major amputation, age, and congestive heart failure
      predicted mortality after minor amputation. The white blood cell count predicted
      in-hospital mortality following both major and minor amputation. However,
      postoperative infection predicted in-hospital mortality only following major
      amputation. Conclusions In-hospital mortality was high after major amputations.
      Unplanned redo-amputation was not a predictor of in-hospital mortality after
      major or minor amputation. Planned staged amputation was associated with reduced
      survival after major but not minor amputation. Postoperative infection predicted
      mortality after major amputation. Systemic diseases and postoperative white blood
      cell were associated with in-hospital mortality. This study suggests a possible
      link between a pro-inflammatory state and increased in-hospital mortality
      following amputation.

PMID- 29041831
TI  - Postoperative complications after lower extremity arterial bypass increase the
      risk of new deep venous thrombosis.
AB  - Background Deep venous thrombosis after any surgical operations is considered a
      preventable complication. Lower extremity bypass surgery is a commonly performed
      operation to improve blood flow to lower extremities in patients with severe
      peripheral arterial disease. Despite advances in endovascular surgery, lower
      extremity arterial bypass remains the gold standard treatment for severe,
      symptomatic peripheral arterial disease. The purpose of this study is to identify
      the clinical risk factors associated with development of deep venous thrombosis
      after lower extremity bypass surgery. Methods The American College of Surgeons'
      NSQIP database was utilized and all lower extremity bypass procedures performed
      in 2013 were examined. Patient and procedural characteristics were evaluated.
      Univariate and multivariate logistic regression analysis was used to determine
      independent risk factors for the development of postoperative deep venous
      thrombosis. Results A total of 2646 patients (65% males and 35% females)
      underwent lower extremity open revascularization during the year 2013. The
      following factors were found to be significantly associated with postoperative
      deep venous thrombosis: transfusion >4 units of packed red blood cells (odds
      ratio (OR) = 5.21, confidence interval (CI) = 1.29-22.81, p = 0.03),
      postoperative urinary tract infection (OR = 12.59, CI = 4.12-38.48, p < 0.01),
      length of hospital stay >28 days (OR = 9.30, CI = 2.79-30.92, p < 0.01), bleeding
      (OR = 2.93, CI = 1.27-6.73, p = 0.01), deep wound infection (OR = 3.21, CI = 1.37
      7.56, p < 0.01), and unplanned reoperation (OR = 4.57, CI = 2.03-10.26, p <
      0.01). Of these, multivariable analysis identified the factors independently
      associated with development of deep venous thrombosis after lower extremity
      bypass surgery to be unplanned reoperation (OR = 3.57, CI = 1.54-8.30, p < 0.01),
      reintubation (OR = 8.93, CI = 2.66-29.97, p < 0.01), and urinary tract infection
      (OR = 7.64, CI = 2.27-25.73, p < 0.01). Presence of all three factors was
      associated with a 54% incidence of deep venous thrombosis. Conclusions
      Development of deep venous thrombosis after lower extremity bypass is a serious
      but infrequent complication. Patients who require unplanned return to the
      operating room, reintubation, or develop a postoperative urinary tract are at
      high risk for developing postoperative deep venous thrombosis. Increased
      monitoring of these patients and ensuring adequate deep venous thrombosis
      prophylaxis for such patients is suggested.

PMID- 29041832
TI  - Enhanced vitamin B12 production in an innovative lupin tempeh is due to synergic
      effects of Rhizopus and Propionibacterium in cofermentation.
AB  - Fermentation represents a valuable and cost-effective approach for food
      stabilisation and nutritional improvement. Tempeh is an example of soybean solid
      state fermentation. In this work, we investigated the possibility of producing a
      tempeh analogue containing high amounts of vitamin B12 using seeds of three
      different species of the legume lupin, namely Lupinus albus, L. angustifolius and
      L. mutabilis, with Rhizopus oligosporus and Propionibacterium freudenreichii
      cofermentation. Synergic effects of Rhizopus and Propionibacterium in increasing
      vitamin B12 up to 1230 ng/g dw was observed. These findings indicate that this
      cofermentation can improve lupin nutritional quality and safety to provide a
      tempeh analogue with added value for vegan and vegetarian communities and low
      income populations. The level of potentially toxic lupin alkaloids was also
      monitored during the tempeh preparation.

PMID- 29041833
TI  - Healthcare costs in patients with advanced non-small cell lung cancer and disease
      progression during targeted therapy: a real-world observational study.
AB  - AIMS: To assess healthcare costs during treatment with epidermal growth factor
      receptor (EGFR) tyrosine kinase inhibitors (TKIs) and following disease
      progression in patients with advanced non-small cell lung cancer (NSCLC).
      METHODS: A retrospective analysis of medical records of US community oncology
      practices was conducted. Eligible patients had advanced NSCLC (stage IIIB/IV)
      diagnosed between January 1, 2008 and January 1, 2015, initiated treatment with
      erlotinib or afatinib (first-line or second-line), and had disease progression.
      Monthly Medicare-paid costs were evaluated during the TKI therapy period and
      following progression. RESULTS: The study included 364 patients. The total mean
      monthly cost during TKI therapy was $20,106 (95% confidence interval [CI] =
      $16,836-$23,376), of which 47.0% and 42.4% represented hospitalization costs and
      anti-cancer therapy costs, respectively. Following progression on TKI therapy
      (data available for 316 patients), total mean monthly cost was $19,274 (95% CI =
      $15,329-$23,218), and was higher in the 76.3% of patients who received anti
      cancer therapy following progression than in the 23.7% of those who did not
      ($20,490 vs $15,364; p < .001). Among patients who received it, anti-cancer
      therapy ($11,198; 95% CI = $7,102-$15,295) represented 54.7% of total mean
      monthly cost. Among patients who did not receive anti-cancer therapy,
      hospitalization ($13,829; 95% CI = $4,922-$22,736) represented 90.0% of total
      mean monthly cost. Impaired performance status and brain metastases were
      significant predictors of increased cost during TKI therapy. LIMITATIONS: The
      study design may limit the generalizability of findings. CONCLUSIONS: Healthcare
      costs during TKI treatment and following progression appeared to be similar and
      were largely attributed to hospitalization and anti-cancer therapy. Notably,
      almost one-quarter of patients did not receive anti-cancer therapy following
      progression, potentially indicating an unmet need; hospitalization was the
      largest cost contributor for these patients. Additional effective targeted
      therapies are needed that could prolong progression-free survival, leading to
      fewer hospitalizations for EGFR mutation-positive patients.

PMID- 29041834
TI  - Quality assessment of the detailed anomaly ultrasound scan.
AB  - OBJECTIVES: The objective of this study is to assess the quality of the views in
      the detailed anomaly ultrasound scan and examine the parameters that influence
      it. METHODS: Prospective study on singleton pregnancies examined at 20-24 weeks.
      Detailed views of all fetal organs were classified by the examiner as
      optimal/suboptimal. The duration of the examination was observed. Maternal
      characteristics, Fat Index (FI) (distance between the skin and the surface of the
      uterus), and fetal position were recorded. RESULTS: The study population
      consisted of 940 singleton pregnancies. Optimal visualization of all fetal
      structures was achieved in 66% of cases. Significant predictors were BMI, FI, and
      fetal position. None of the women with BMI >= 44 and none of the women with FI >=
      60 mm had optimal visualization of all fetal structures. Median duration of the
      examination was 23 min. In 75% of cases, it was completed in the first attempt.
      Maternal weight, FI, and fetal position were the significant independent
      predictors of total examination time. CONCLUSIONS: Optimal visualization of the
      fetal anatomy is restricted by maternal parameters and fetal position. The main
      limitation is accumulation of abdominal fat, usually but not always related to
      maternal obesity. The FI may be recorded as a measure of technical difficulty.
      The anomaly scan should be allocated at least 30 min scanning time.

PMID- 29041835
TI  - Assessment of executive function in ADHD adolescents: contribution of performance
      tests and rating scales.
AB  - This study aimed to analyze performance on measures of neuropsychological and
      behavioral executive functions (EF) in adolescents with attention deficit
      hyperactivity disorder (ADHD), and to evaluate the utility of performance-based
      tests for predicting scores on behavioral EF ratings. One hundred eighteen
      adolescents (75 ADHD and 43 controls) aged 12-16 years performed
      neuropsychological tests and completed a behavior rating scale of EF. The ADHD
      group presented significantly lower scores than controls on Full Scale IQ (FSIQ)
      and all indexes of the WISC-IV, except the verbal comprehension index (VCI). The
      ADHD group had significantly lower scores on performance-based tests of working
      memory, planning and inhibition, and on EF rating scales. Scores on the cognitive
      EF working memory, planning and flexibility modestly predicted performance on
      behavioral EF. The results suggest that the combined use of performance-based
      tests and rating scales provides valuable complementary information that can
      improve the assessment of executive domains in ADHD.

PMID- 29041836
TI  - Influence of visual clutter on the effect of navigated safety inspection: a case
      study on elevator installation.
AB  - INTRODUCTION: Navigated safety inspection based on task-specific checklists can
      increase the hazard detection rate, theoretically with interference from scene
      complexity. Visual clutter, a proxy of scene complexity, can theoretically impair
      visual search performance, but its impact on the effect of safety inspection
      performance remains to be explored for the optimization of navigated inspection.
      This research aims to explore whether the relationship between working memory and
      hazard detection rate is moderated by visual clutter. METHODS: Based on a
      perceptive model of hazard detection, we: (a) developed a mathematical influence
      model for construction hazard detection; (b) designed an experiment to observe
      the performance of hazard detection rate with adjusted working memory under
      different levels of visual clutter, while using an eye-tracking device to observe
      participants' visual search processes; (c) utilized logistic regression to
      analyze the developed model under various visual clutter. CONCLUSION: The effect
      of a strengthened working memory on the detection rate through increased search
      efficiency is more apparent in high visual clutter. This study confirms the role
      of visual clutter in construction-navigated inspections, thus serving as a
      foundation for the optimization of inspection planning.

PMID- 29041837
TI  - Infective keratitis in Indian patients with corneal dystrophies.
AB  - All eight patients seen with various types of corneal dystrophy, a rare
      hereditary corneal disease, presented with infective keratitis. Unilateral
      microbial invasion was seen in all patients and the visual acuity of the affected
      eyes was <6/60 at presentation. We highlight our impression that microbial
      invasion can occur with all types of epithelial and stromal corneal dystrophy,
      including macular corneal dystrophy. Regular follow-up to maintain a healthy
      ocular surface is recommended to avert blindness in such patients.

PMID- 29041838
TI  - Psychodermatology liaison clinic in India: a working model.
AB  - Literature reports suggest that up to 30% of dermatology patients have associated
      psychiatric co-morbidity. A psychodermatology liaison (PD) clinic is essential to
      deal with such patients, which is almost non-existent in the Indian scenario. In
      order to report the working pattern of such a clinic and to determine its
      efficacy with the help of Dermatology Life Quality Index (DLQI) and Short
      Assessment of Patient Satisfaction (SAPS) questionnaires, we investigated
      patients with suspected psychocutaneous diseases in an open-labelled two-year
      prospective study. Of 236 patients, 86 had psychiatric co-morbidity, 19 had
      primary psychiatric disorders, 144 were advised psychological interventions and
      98 were prescribed psychotropics. A statistically significant fall in DLQI scores
      at follow-up indicated improvement in quality of life. SAPS scales demonstrated
      87.3% of patients in our PD clinic were satisfied with their management in
      contrast to 53.8% patients in the normal standard dermatology clinic. Nearly 33%
      of the patients attending our PD clinic had psychiatric co-morbidity, the
      commonest being an adjustment disorder.

PMID- 29041839
TI  - Imitation-tumor targeting based on continuous-wave near-infrared tomography.
AB  - Continuous-wave Near-Infrared (NIR) optical spectroscopy has shown great
      diagnostic capability in the early tumor detection with advantages of low-cost,
      portable, non-invasive, and non-radiative. In this paper, Modified Lambert-Beer
      Theory is deployed to address the low-resolution issues of the NIR technique and
      to design the tumor detecting and imaging system. Considering that tumor tissues
      have features such as high blood flow and hypoxia, the proposed technique can
      detect the location, size, and other information of the tumor tissues by
      comparing the absorbance between pathological and normal tissues. Finally, the
      tumor tissues can be imaged through tomographic method. The simulation
      experiments prove that the proposed technique and designed system can efficiently
      detect the tumor tissues, achieving imaging precision within 1 mm. The work of
      the paper has shown great potential in the diagnosis of tumor close to body
      surface.

PMID- 29041840
TI  - Identification of novel scaffolds to inhibit human mitotic kinesin Eg5 targeting
      the second allosteric binding site using in silico methods.
AB  - Human mitotic kinesins are potential anticancer drug targets because of their
      essential role in mitotic cell division. The kinesin Eg5 (Kinesin-5, kif11) has
      gained much attention in this regard and has many inhibitors in different phases
      of clinical trials. All drug candidates considered for Eg5 so far binds to the
      binding site (Site 1) formed by the loop L5, helices alpha2 and alpha3 and are
      uncompetitive to ATP/ADP. Recently, it has been reported that Eg5 also has a
      second binding site (Site 2) formed by helices alpha4 and alpha6. In the current
      work, we have screened the compounds in the diversity set-III from National
      Cancer Institute (NCI) and Zinc database to identify potential inhibitors for Eg5
      that specifically binds to the site 2. The compounds were ranked based on the
      glide extra precision docking scores and the top ranked compounds were found to
      have pyridazine scaffold. The top five compounds were further evaluated for other
      drug like properties. Stability of protein-ligand complexes were analyzed using
      molecular dynamic simulations. Our studies suggest that pyridazine analogs have
      good MDCK, permeability properties and high binding affinity to the human Eg5.

PMID- 29041841
TI  - Effect of home telehealth care on blood pressure control: A public healthcare
      centre model.
AB  - Objective This study aimed to evaluate the effectiveness of home telehealth care
      combined with case management by public health nurses, in improving blood
      pressure control in patients with hypertension. Methods This cohort study
      examined the data of patients with hypertension obtained from a telehealth
      service centre database, between July 2011- June 2012. Eligible patients were
      adults (>=40 years old) with both prehypertension and hypertension, living alone
      or in the remote suburbs of metropolitan areas. Demographic data were collected
      from 12 district public health centre in Taipei, Taiwan. Following enrolment,
      patients received an appropriate and validated home telehealth device kit for
      automatic blood pressure monitoring and automated modem via a telephone line or a
      desktop computer with Internet connection to enable data transmission between the
      patient's home and telehealth service centre. Patients were instructed to upload
      the measured data immediately every day. The study outcomes included blood
      pressure and home telehealth service utilisation. Results Of the 432 patients
      recruited, 408 (94%) completed data collection. Linear regression analysis found
      an average 22.1 mm Hg reduction in systolic blood pressure after one year. The
      mean slope of systolic blood pressure was classified as decreased or non
      decreased. An systolic blood pressure decreasing trend was observed in 52.2%
      patients, while 47.8% patients showed an increasing systolic blood pressure
      trend. Patients in the decreased systolic blood pressure group tended to be older
      ( p = 0. 0001), with a greater proportion of hypertension alarms ( p = 0. 001),
      improved self-blood pressure monitoring behaviour ( p = 0.009) and higher self
      measured blood pressure monitoring frequency ( p = 0. 010). Patients in the
      decreased systolic blood pressure group had a higher self-measured blood pressure
      monitoring frequency (odds ratio = 0.95, 95% confidence interval, 0.91-0.99, p =
      0. 013) than their counterparts. Conclusions Home telehealth care combined with
      care management by public health nurses based in public health care centre was
      feasible and effective for improving blood pressure control among patients with
      hypertension. Further studies should conduct a thorough analysis of the cost
      effectiveness of this intervention. A randomised controlled trial with a longer
      follow-up period is required to examine the effects of the improved home
      telehealth device kit on the care of patients with hypertension.

PMID- 29041843
TI  - Embryo transfer is a risk factor for severe postpartum hemorrhage and blood
      transfusion requirement.
AB  - PURPOSE: This study aimed to investigate the risk factors for severe postpartum
      hemorrhage (PPH) and blood transfusion requirement that are recognizable during
      any period of pregnancy. MATERIALS AND METHODS: We retrospectively reviewed the
      medical data of 4829 pregnant women who received care and delivered at our
      institution between July 2010 and March 2015. The cohort was divided into
      patients with and without severe PPH. Multivariate logistic regression analysis
      was performed to assess risk factors associated with severe PPH. The same
      analysis was repeated for blood transfusion requirement. RESULTS: A total of 127
      (2.7%) patients had severe PPH and 43 (0.87%) required blood transfusion. The
      multivariate logistic regression analysis demonstrated that embryo transfer (odds
      ratio [OR] 2.6; p < .001), uterine myoma (OR 2.0; p < .01), prior uterine surgery
      (OR 1.9; p = .03), prior cesarean section (OR 1.8; p = .01), and maternal age (OR
      1.5; p = .03) were independent risk factors for severe PPH. Embryo transfer was
      an independent risk factor for blood transfusion requirement (OR 3.1, p < .001).
      CONCLUSIONS: Embryo transfer is a risk factor for both severe postpartum
      hemorrhage and blood transfusion requirement.

PMID- 29041842
TI  - Identifying novel small molecule antagonists for mLST8 protein using
      computational approaches.
AB  - Mammalian lethal with SEC13 protein 8 (mLST8), is an indispensable protein
      subunit of mammalian target of rapamycin (mTOR) signaling pathway that interacts
      with the kinase domain of mTOR protein, thereby stabilizing its active site.
      Experimental studies reported the over expression of mLST8 in human colon and
      prostate cancers by activation of both mTORC1/2 complexes and subsequent
      downstream substrates leading to tumor progression. Considering its role,
      targeting mLST8 protein would be a therapeutic approach against tumor progression
      in colon and prostate cancers. Hence, using in silico structure based drug design
      approach, the comparative binding patterns of 1,1'-binapthyl-2,2'diol (BINOL), 1
      (2-carboxynaphth-1yl)-2-naphthoic acid (SCF-12) and their analogs in the cavity
      of mLST8 were explored. ADME and binding energy calculations led to the
      identification of five compounds with favorable Glide (G) scores and implicated
      the importance of Asn132 and Gln225 as key binding residues. Molecular dynamics
      (MD) simulations and free energy landscape (FEL) approaches helped in elucidating
      the binding mechanism and suggested the possibility of ligands 1-3 namely,
      ZINC01765622, ZINC62723702 and ZINC02576980 to be promising antagonists for
      mLST8. Thus, this study substantiates the prospect of targeting mLST8 protein
      using potent hits which could hinder tumor progression in colon and prostate
      cancers.

PMID- 29041844
TI  - Reduced expression of NR4A1 activates glycolytic pathway in acute promyelocytic
      leukemia cells.

PMID- 29041845
TI  - Relationship between oxidative stress and erectile function.
AB  - The aim of this study was to investigate markers of inflammation and oxidative
      stress in the corpus cavernosum (CC) and to compare levels of inflammatory
      markers recorded in CC to venous blood from the arm to examine the potential
      impact of inflammatory parameters on erectile function and endothelial
      dysfunction in vitro. Ninety-seven patients with no complaint of erectile
      dysfunction (ED) at inclusion were prospectively included and completed the
      Erectile Function domain of the IIEF questionnaire. Several parameters, including
      lipids, MPO-dependent oxidised LDL (Mox-LDL), IL-8, IL-18, were measured. After
      RNA extraction, the expression of eNOS was analysed. A paired t-test was used for
      comparisons between arm and CC blood results. A two-way ANOVA was used to
      estimate the effects of IL-18 and IL-8 on the IIEF score. Mean patient age was 59
      +/- 14.5 years. IL-18, Mox-LDL, and Mox-LDL/ApoB levels were significantly
      increased in CC compared to arm blood. The IIEF score was correlated with IL-18
      levels in the venous blood (R = -0.31, p = .003) and in the CC (R = -0.37, p =
      .004) and with IL-8 (R = -0.31, p = .009 and R = -0.28, respectively, p = .02).
      There was a significant effect with the IL-18 on IIEF potentiated by high serum
      IL-8 concentrations. IL-18 and Mox-LDL significantly decreased eNOS mRNA
      expression in human aortic endothelial cell line (HAEC). These preliminary
      results address the importance of inflammation in the CC and highlight a
      difference in marker concentrations between venous and CC blood. However, they do
      not show any difference in terms of clinical erectile score predictivity.
      Involvement of inflammatory cytokines isolated in CC in the genesis of ED
      requires further studies.

PMID- 29041847
TI  - ?

PMID- 29041846
TI  - ?

PMID- 29041848
TI  - ?

PMID- 29041850
TI  - ?

PMID- 29041849
TI  - ?

PMID- 29041852
TI  - ?

PMID- 29041851
TI  - ?

PMID- 29041853
TI  - ?

PMID- 29041854
TI  - ?

PMID- 29041855
TI  - ?

PMID- 29041857
TI  - ?

PMID- 29041856
TI  - ?

PMID- 29041858
TI  - ?

PMID- 29041859
TI  - ?

PMID- 29041860
TI  - Maternal behavior of the mouse dam toward pups: implications for maternal
      separation model of early life stress.
AB  - Maternal care is essential for an adequate pup development, as well as for the
      health of the dam. Exposure to stress in early stages of life can disrupt this
      dam-pup relationship promoting altered neurobiological and behavioral phenotypes.
      However, there is a lack of consensus regarding the effects of daily maternal
      separation (MS) on the pattern of maternal behavior. The aim of this study is to
      compare the patterns of maternal behavior between mice exposed to MS and
      controls. BALB/c mice were subjected to MS for a period of 180 min/day from
      postnatal day 2-7 (n = 17) or designated to be standard animal facility reared
      (AFR) controls (n = 19). Maternal behaviors were computed as frequency of
      nursing, licking pups and contact with pups, and nonmaternal behaviors were
      computed as frequency of actions without interaction with pups and
      eating/drinking. A total of 18 daily observations of maternal behavior were
      conducted during these six days, and considering the proportion of maternal and
      nonmaternal behaviors, an index was calculated. There was no difference when
      comparing the global index of maternal behavior between the AFR and MS animals by
      the end of the observed period. However, the pattern of maternal behavior between
      groups was significantly different. While MS dams presented low frequency of
      maternal behavior within the first couple days of the stress protocol, but
      increasing over time, AFR dams showed higher maternal behavior at the beginning,
      reducing over time. Together, our results indicate that MS alters the maternal
      behavior of the dams toward pups throughout the first week of the stress protocol
      and provoked some anxiety-related traits in the dams. The inversion of maternal
      behavior pattern could possibly be an attempt to compensate the low levels of
      maternal care observed in the first days of MS.

PMID- 29041861
TI  - In vitro evaluation of aerosol delivery of aztreonam lysine (AZLI): an adult
      mechanical ventilation model.
AB  - BACKGROUND: The delivery profile of Aztreonam lysine (AZLI) during mechanical
      ventilation (MV) is unknown. We evaluated the amount of AZLI drug delivered using
      an in vitro model of adult MV. METHODS: An adult lung model designed to mimic
      current clinical practice was used. Both nebulizers were placed before a Y-piece
      and 4 settings were tested: A) Aeroneb solo(r) [AS] with a t-piece; B) AS with
      the spacer; C) M-Neb(r) [MN] with a t-piece and D) MN with the spacer.
      Performance was evaluated in terms of: 1) Mass median aerodynamic diameter
      (MMAD); 2) Geometric standard deviation (GSD), 3) Fine particle dose (FPD), 4)
      Fine particle fraction (FPF), 5) Inhalable mass (IM), and 6) Recovery rate (RR).
      RESULTS: Both devices showed an adequate delivery of AZLI during MV, with MMAD
      between 2.4-2.5 um and 87% of FPF. The FPD (38.8 and 31.7), IM (44.8 and 36.1)
      and RR (30 and 24) were similar for AS and MN respectively. Nebulizer aerosol
      delivery increased (50 and 70% respectively) for both nebulizers when using the
      spacer. CONCLUSION: Both AS and MN showed a good aerosol delivery profile for
      AZLI during in vitro mechanical ventilation. Better aerosol delivery performance
      was obtained using the spacer.

PMID- 29041862
TI  - Impact of chronic maternal stress during early gestation on maternal-fetal stress
      transfer and fetal stress sensitivity in sheep.
AB  - Acute stress-induced reduction of uterine blood flow (UBF) is an indirect
      mechanism of maternal-fetal stress transfer during late gestation. Effects of
      chronic psychosocial maternal stress (CMS) during early gestation, as may be
      experienced by many working women, on this stress signaling mechanism are
      unclear. We hypothesized that CMS in sheep during early gestation augments later
      acute stress-induced decreases of UBF, and aggravates the fetal hormonal,
      cardiovascular, and metabolic stress responses during later development. Six
      pregnant ewes underwent repeated isolation stress (CMS) between 30 and 100 days
      of gestation (dGA, term: 150 dGA) and seven pregnant ewes served as controls. At
      110 dGA, ewes were chronically instrumented and underwent acute isolation stress.
      The acute stress decreased UBF by 19% in both the CMS and control groups (p <
      .05), but this was prolonged in CMS versus control ewes (74 vs. 30 min, p < .05).
      CMS increased fetal circulating baseline and stress-induced cortisol and
      norepinephrine concentrations indicating a hyperactive hypothalamus-pituitary
      adrenal (HPA)-axis and sympathetic-adrenal-medullary system. Increased fetal
      norepinephrine is endogenous as maternal catecholamines do not cross the
      placenta. Cortisol in the control but not in the CMS fetuses was correlated with
      maternal cortisol blood concentrations; these findings indicate: (1) no increased
      maternal-fetal cortisol transfer with CMS, (2) cortisol production in CMS fetuses
      when the HPA-axis is normally inactive, due to early maturation of the fetal HPA
      axis. CMS fetuses were better oxygenated, without shift towards acidosis compared
      to the controls, potentially reflecting adaptation to repeated stress. Hence, CMS
      enhances maternal-fetal stress transfer by prolonged reduction in UBF and
      increased fetal HPA responsiveness.

PMID- 29041863
TI  - Clinical outcome measures for progressive MS trials.
AB  - Treatment options for progressive multiple sclerosis remain the main unmet need
      of the field. As the understanding of multiple sclerosis (MS) pathogenesis
      improves, new pathways and molecules will be tested for potential reparative,
      remyelinating, or neuroprotective effects. The clinical outcomes used will
      determine successful demonstration of beneficial treatment effects to regulatory
      agencies, clinicians, and persons with MS. This review focuses on clinical
      outcome measures including the Expanded Disability Status Scale, Multiple
      Sclerosis Functional Composite, and novel composite measures of disability. The
      paper also covers cognitive outcomes and screening tests for use in clinical
      trials. The growing importance of patient-reported outcomes and their suitability
      for clinical trials is also presented. The review aims to create consensus in
      regard to these topics and suggestions for future research.

PMID- 29041864
TI  - Targets of therapy in progressive MS.
AB  - Highly effective anti-inflammatory therapies have so far been developed for
      patients with relapsing/remitting multiple sclerosis, which also show some
      benefits in the early progressive stage of the disease. However, treatment
      options for patients, who have entered the progressive phase, are still limited.
      Disease starts as an inflammatory process, which induces focal demyelinating
      lesions in the gray and white matter. This stage of the disease dominates in the
      relapsing phase, extends into the early stages of progressive disease, and can be
      targeted by current anti-inflammatory treatments. In parallel, inflammation
      accumulates behind a closed or repaired blood brain barrier, and this process
      peaks in the late relapsing and early progressive stage and then declines. Some
      data suggest that this process may be targeted by immune ablation and
      hematopoietic stem cell transplantation. In the late stage, inflammation may
      decline to levels seen in age-matched controls, but age and disease burden
      related neurodegeneration ensues. Such neurodegeneration affects the damaged
      brain and spinal cord, in which functional reserve capacity is exhausted, giving
      rise to further disability progression. Anti-inflammatory treatments are unlikely
      to be beneficial in this stage of the disease, but neuroprotective and repair
      inducing strategies may still be effective.

PMID- 29041866
TI  - 'Progressive MS - macro views': The need for novel clinical trial paradigms to
      enable drug development for progressive MS.
AB  - This article outlines the principal challenges to establish a standard phase-2
      approach for progressive multiple sclerosis (PMS) and presents referring
      strategies to accelerate the registration process via a guidance approved by
      regulatory agencies. Accordingly, the contribution of 'big datasets' for a better
      understanding of the natural history of primary-progressive multiple sclerosis
      (PPMS) and secondary-progressive multiple sclerosis (SPMS) and of their
      prognostic factors and the value of novel biomarkers are discussed. The
      establishment of new industry-academic initiatives, such as independent consortia
      under the umbrella of Progressive MS Alliance (PMSA), with the endorsement of MS
      organizations and Scientific Societies (e.g. European Committee for Treatment and
      Research in Multiple Sclerosis (ECTRIMS)) may be crucial to overcome some of the
      current challenges. Within this frame, the continuous interaction with regulatory
      agencies is instrumental for the formal validation of the many developments
      suitable to improve clinical trialling in PMS.

PMID- 29041867
TI  - Patient selection for trials.
AB  - The last several decades have witnessed considerable progress in our
      understanding of the pathogenesis, refining diagnostic criteria, and identifying
      therapies of value for modifying the course of relapsing forms of multiple
      sclerosis. While the pace of progress has lagged for those with progressive phase
      disease, this now seems to be changing. This review considers those
      characteristics of patients with primary progressive multiple sclerosis that may
      contribute to phase 3 trial success and identifies some of the thorny issues that
      remain ahead. The larger of the studies conducted thus far have sequentially
      informed our understanding of "pure" primary progressive disease, and also
      challenge both phase 3 and especially phase 2 trial designs and participant
      selection for investigations going forward. This may have particular relevance
      for testing therapeutics directed at neuroprotection and repair in the face of
      ongoing progression regardless of trial participant categorization using current
      conventional disease phenotypes.

PMID- 29041865
TI  - Imaging outcome measures for progressive multiple sclerosis trials.
AB  - Imaging markers that are reliable, reproducible and sensitive to
      neurodegenerative changes in progressive multiple sclerosis (MS) can enhance the
      development of new medications with a neuroprotective mode-of-action.
      Accordingly, in recent years, a considerable number of imaging biomarkers have
      been included in phase 2 and 3 clinical trials in primary and secondary
      progressive MS. Brain lesion count and volume are markers of inflammation and
      demyelination and are important outcomes even in progressive MS trials. Brain
      and, more recently, spinal cord atrophy are gaining relevance, considering their
      strong association with disability accrual; ongoing improvements in analysis
      methods will enhance their applicability in clinical trials, especially for cord
      atrophy. Advanced magnetic resonance imaging (MRI) techniques (e.g. magnetization
      transfer ratio (MTR), diffusion tensor imaging (DTI), spectroscopy) have been
      included in few trials so far and hold promise for the future, as they can
      reflect specific pathological changes targeted by neuroprotective treatments.
      Position emission tomography (PET) and optical coherence tomography have yet to
      be included. Applications, limitations and future perspectives of these
      techniques in clinical trials in progressive MS are discussed, with emphasis on
      measurement sensitivity, reliability and sample size calculation.

PMID- 29041868
TI  - The evolving role of people with MS in clinical research-Some progress but more
      is needed.
AB  - People with multiple sclerosis (MS) have been participants in clinical trials
      over many years, enabling the development and approval of many treatments for
      relapsing-remitting MS. Today, people with MS expect to be active collaborators
      in clinical trials and throughout the research and development process.
      Researchers and clinicians can benefit from including people with MS in all
      aspects of research and trials, and are urged to do so, so that we can move
      forward more quickly in developing needed treatments for progressive MS.

PMID- 29041869
TI  - Advancing trial design in progressive multiple sclerosis.

PMID- 29041870
TI  - Fluid biomarker and electrophysiological outcome measures for progressive MS
      trials.
AB  - Progressive multiple sclerosis (MS) is characterized by insidious clinical
      worsening that is difficult to accurately quantify and predict. Biofluid markers
      and electrophysiological measures are potential candidate outcome measures in
      clinical trials, allowing the quantification of nervous damage occurring in the
      disease. Neurofilaments are highly specific neuronal proteins. They may have come
      closest to such applications by their higher concentrations repeatedly
      demonstrated in cerebrospinal fluid (CSF) in all stages of MS, during relapses,
      their responsiveness to disease-modifying treatments in relapsing and progressive
      MS and their associations with measures of inflammatory and degenerative magnetic
      resonance imaging (MRI) outcomes. Digital single-molecule array (Simoa)
      technology improves accuracy of bioassays in the quantification of neurofilament
      light chain (NfL) in serum and plasma. NfL seems to mark a common final path of
      neuroaxonal injury independent of specific causal pathways. CSF and blood levels
      of NfL are highly correlated across various diseases including MS, suggesting
      that blood measurements may be useful in assessing response to treatment and
      predicting future disease activity. Other biomarkers like matrix
      metalloproteinases, chemokines, or neurotrophic factors have not been studied to
      a similar extent. Such measures, especially in blood, need further validation to
      enter the trial arena or clinical practice. The broadening armamentarium of
      highly sensitive assay technologies in the future may shed even more light on
      patient heterogeneity and mechanisms leading to disability in MS. Evoked
      potentials (EPs) are used in clinical practice to measure central conduction of
      central sensorimotor pathways. They correlate with and predict the severity of
      clinical involvement of their corresponding function. Their validation for use in
      multicenter studies is still lacking, with the exception of visual EPs. If
      further validated, EPs and fluid biomarkers would represent useful outcome
      measures for clinical trials, being related to specific mechanisms of the ongoing
      pathologic changes.

PMID- 29041871
TI  - Advancing trial design in progressive multiple sclerosis.
AB  - The failure of a majority of clinical trials in progressive multiple sclerosis
      (MS) has highlighted the need to reconsider how these trials are designed and
      conducted, and many areas deserve focus. Basic scientists are reconceptualising
      the pathophysiology of progressive MS into three broad areas: systemic
      inflammation, compartmentalized inflammation and non-inflammatory
      neurodegeneration, with the latter two becoming predominant as the disease
      progresses. This framework will guide the choice of experimental therapies.
      Previous clinical trials have highlighted how participant selection can have a
      significant impact on study outcome. Phase 2 biomarkers which are biologically
      stable, dynamically changing over time, and easy to assess in multi-centre
      studies are greatly needed. Shortcomings inherent in the Expanded Disability
      Status Scale are prompting the development and validation of better clinical
      measures. The standard two-arm, fixed-duration trial paradigm has been challenged
      with new, innovative approaches that can test more therapies efficiently.
      International collaboratives such as the Progressive MS Alliance will support
      increased dialogue with regulators, industry and other funding agencies. Better
      engagement with people living with progressive MS will transform them from simply
      being the recipient of MS therapies to partners in the search for new treatments.
      Focused, targeted action will drive further development of effective therapies
      for progressive MS.

PMID- 29041872
TI  - Progressive MS trials: Lessons learned.
AB  - Up to very recently, no treatments had proved effective in progressive multiple
      sclerosis (MS). In 2016, four drugs, two tested in phase 3 and two in phase 2
      trials, showed a beneficial effect in primary or secondary progressive MS.
      Although this could indicate a turning point in progressive MS treatment, most of
      these successes have been modest and mainly restricted to patients with active
      inflammation, in the context of trials with powerful anti-inflammatory agents.
      This paper summarises these reasons, particularly focusing on the main lessons
      learned for the design of future trials. First, a drug's mechanism of action
      should tackle the specific pathogenic mechanisms that characterise progressive
      MS. Second, trial populations where new drugs are to be tested should be
      carefully chosen, possibly including younger patients with shorter disease
      durations, which have greater chances of showing active deterioration during the
      trial, therefore increasing the power to detect treatment effects. Third, outcome
      measures used in future phase 2 and phase 3 trials should be highly sensitive and
      be accompanied by smart trial designs.

PMID- 29041873
TI  - Clinical trial design for progressive MS trials.
AB  - The design of clinical trials is a key aspect to maximizing the possibility to
      detect a treatment effect. This fact is particularly challenging in progressive
      multiple sclerosis (PMS) studies due to the uncertainty about the right target
      and/or outcome in phase-2 studies. The aim of this review is to evaluate the
      current challenges facing the design of clinical trials for PMS. The selection of
      patients, the instrumental and clinical outcomes that can be used in PMS trials,
      and issues in their design will be covered in this report.

PMID- 29041874
TI  - Editorial: New Experimental and Computational Tools for Drug Discovery: From
      Chemistry to Biology. Part-II.

PMID- 29041875
TI  - [Myocardial Perfusion Imaging Modalities: What do we Really see?]
AB  - Assessment of perfusion, severity of ischemia and the volume of viable
      myocardium, including single-photon or positron emission tomography (SPECT and
      PET) is one of the most important stages of examination of patients with ischemic
      heart disease. However, in recent years "perfusion" prefix was added to other
      cardiologic modalities (echocardiography, magnetic resonance and computed
      tomography). Such a terminological uncertainty leads cardiologists to an
      erroneous evaluation of real possibilities of these methods. The review clarifies
      the definitions of terms "perfusion", "ischemia", and "viability" of the
      myocardium. Imaging modalities are compared from the perspective of compliance
      with the kinetics of the indicators used and actually visualized myocardial
      processes.

PMID- 29041876
TI  - [Stress Echocardiography in the Assessment of Long-Term Outcomes After
      Percutaneous Coronary Intervention in Patients With Stable Coronary Heart
      Disease].
AB  - AIM: To study the possibilities of stress echocardiography (EchoCG) in the
      assessment of clinical state of patients after percutaneous coronary intervention
      (PCI). MATERIAL AND METHODS: We included into this study 80 patients with stable
      ischemic heart disease. After preliminary examination, all patients underwent
      PCI. Stress EchoCG was carried out in 6 and 12 months after PCI. RESULTS:
      Clinical effect assessed in 12 months after revascularization was good in 90% of
      patients. We registered significant increase of exercise capacity (from 97 to 118
      W; p=0.001), increase of double product (from 232 to 275; p=0.009), decrease of
      myocardial ischemia volume (regional contractility impairment index before PCI
      1.36, a year after PCI 1.16; p=0.001). The incidence of restenosis was 7.5%.
      Restenosis was accompanied by a deterioration of clinical status of patients
      (silent myocardial ischemia, angina recurrence). The accuracy of stress
      echocardiography in detecting myocardial ischemia in patients after PCI was 94%.
      CONCLUSION: Stress EchoCG has high diagnostic accuracy for detection of
      myocardial ischemia in patients after PCI during the first 12 months after
      revascularization.

PMID- 29041877
TI  - [Myocardial Infarction at the Background of Left Bundle Branch Block in the
      RECORD-3 Registry - Management and Prognosis].
AB  - PURPOSE: To study prognostic value of left bundle brunch block (LBBB) in patients
      with verified myocardial infarction in real clinical practice. MATERIAL AND
      METHODS: This analysis has been based on data from the RECORD-3 registry. This
      registry enrolled consecutive patients hospitalized in participating centers with
      suspected acute coronary syndrome. Among 2368 included patients 91 (3.84%) had
      LBBB on admission ECG ("new" in 25 [27.4%], "old" in 28 [30.8%]), and of
      "undetermined duration" in 38 [41.8%]). Myocardial infarction (MI) was verified
      in 871 patients, 48 of them (5.5%) had LBBB. RESULTS: MI patients with compared
      with those without LBBB were significantly older (70.5 vs. 64 years, p=0.011),
      more often had history of MI and cerebral catastrophes, effort angina, symptoms
      of chronic heart failure and renal pathology. Patients with LBBB twice more often
      complained of dyspnea/suffocation and had significantly lower mean ejection
      fraction (44 vs 52%, p=0.001). At prehospital stage, they less often received
      aspirin, clopidogrel, beta-adrenoblockers. Patients with LBBB more often required
      artificial pulmonary ventilation (APV) and temporary cardiac pacing, and were
      less often subjected to reperfusion strategy (52.1 vs. 85%, p.

PMID- 29041878
TI  - [Influence of Sympathetic Denervation of the Renal Artery on the Level of
      Arterial Blood Pressure, Cerebral Blood Flow and Cognitive Function In Patients
      With Resistant Arterial Hypertension].
AB  - PURPOSE: To study the effect of radiofrequency ablation of renal arteries on
      regional cerebral blood flow and cognitive function in patients with resistant
      arterial hypertension (AH). MATERIAL AND METHODS: Transcatheter renal denervation
      (TRD) was performed in 17 patients with resistant AH. Examination before and
      after TRD included SPECT with mTc-HMPAO, 24-hours blood pressure (BP) monitoring,
      and comprehensive neuropsychological testing. Fifteen patients without
      angiographic signs of carotid atherosclerosis, coronary artery disease and AH,
      neurological and psychiatric disorders were investigated as control group.
      RESULTS: Compared with control group patients with AH had decreases of regional
      cerebral blood flow (rCBF) in right (by 13.5%, p=0.00002) and left (by 15.5%,
      p=0.0006) inferior frontal lobes, in right temporal brain region (by 11.5%,
      p=0.008); in right and left occipital lobes (by 8.2%, p=0.04). In 6 months after
      TRD we observed significant improvement of cognitive function, parameters of 24
      hour BP monitoring, and rCBF. We also noted definite close interdependence
      between changes of rCBF, indices of 24-hours BP monitoring, and dynamics of
      cognitive function. Improvement of long-term verbal memory correlated with
      increases of rCBF in left superior frontal and right occipital regions while
      dynamics of mentation and attention correlated positively with augmentation of
      rCBF in right posterior parietal region. Changes of perfusion in inferior parts
      of left frontal lobe and in right occipital region correlated with dynamics of
      index of diurnal diastolic hypertension time (R2=0.64, p=0.001, and R2=0.60,
      p=0.03, respectively). CONCLUSION: Our results suggest, that in patients with
      resistant AH positive effect of TRD on levels of 24-hour mean BP as well as on
      indices of BP load leads to in augmentation of rCBF and improvement of cognitive
      function.

PMID- 29041879
TI  - [Adherence to Therapy in the Outpatient Setting: the Ability to Identify and
      Assess the Effectiveness of Therapy].
AB  - AIM: To assess adherence of patients to antihypertensive therapy, to determine
      the role of various factors affecting adherence to treatment by outpatients, and
      to assess clinical efficacy of a calcium antagonist felodipine. MATERIAL AND
      METHODS: We examined 5 474 women and men aged >18 years who at visit to a local
      internist had office systolic arterial pressure (AP) 140-179 and diastolic AP up
      to 100 mm Hg both on and without hypotensive therapy. Examination included
      registration of risk factors and concomitant therapy. All patients self-assessed
      their state of heath using visual analog scale (VAS). Adherence to therapy was
      evaluated by the Morisky-Green test. Obtaining by a patient of antihypertensive
      drugs in the framework of the Programme for Supplementary Pharmaceutical
      Provision (SPP) was necessarily registered. RESULTS: Among examined ambulatory
      patients with arterial hypertension (AH) and ischemic heart disease (IHD) more
      than 60% had low adherence to prescribed medications. Such factors as complicated
      AH course when AH was combined with IHD or diabetes (D), use of angiotensin
      converting enzyme inhibitors, calcium antagonists, and angiotensin receptor
      blockers were associated with high adherence to treatment. Male sex, elderly age,
      presence of risk factors of cardiovascular complications, and long history of AH
      were associated with low adherence to therapy. Presence of prescribed drugs in
      the SSP list was associated with high adherence but multifactorial analysis with
      inclusion of IHD, D, availability of a tonometer at home made contribution of SSP
      in high adherence insignificant. The use of felodipine allowed not only to
      achieve pronounced hypotensive effect in patients with AH but also to improve
      initially low adherence. CONCLUSION: During long-term observation of outpatients,
      it is necessary to regularly assess possibly low adherence to therapy with the
      aim of its improvement.

PMID- 29041880
TI  - [Efficacy of Antihypertensive Therapy Combined With Psychotropic Drugs in
      Patients With Hypertension and Affective Disorders].
AB  - AIM: To compare effects of isolated antihypertensive therapy (AHT) and AHT
      combined with anxiolytic and antidepressant on parameters of 24-hour blood
      pressure (BP) profile, severity of affective disorders, and quality of life (QL)
      in patients with uncontrolled arterial hypertension (AH) and anxiety or
      depressive disorders. MATERIAL AND METHODS: We randomized 140 patients (age
      48.6+/-5.9 year, 72 women) into 2 groups. During 1 year patients of each group
      received 2 variants of pharmacotherapy: isolated AHT and AHT combined with
      psychotropic medication (PM) - anxiolytic for persons with anxiety disorder and
      antidepressant for persons with depressive disorder (AHT+PM). Patients of group I
      received AHT for first 6 months and AHT+PM for remaining 6 months. Group II
      patients started with AHT+PM and after 6 months switched to AHT. In each group we
      selected subgroups of patients with prevailing anxiety (I-A, II-A) and prevailing
      depression (I-D, II-D). In the end of each 6 months period we compared parameters
      of 24-hour BP monitoring, severity of affective disorders, and QL in subgroups IA
      vs. II-A and ID vs. IID. Same comparisons were done for each subgroup in the end
      of the first and second stages of treatment. RESULTS: Starting with combination
      AHT provided more rapid achievement of low values of average diurnal and
      nocturnal systolic (S) and diastolic (D) BP, lower parameters of BP variability.
      In patients with comorbid depression it led to lowering of magnitude and velocity
      of morning increment of SBP and DBP. Only combination AHT demonstrated adequate
      reduction of affective disorders. Both combination and isolated AHT in 6 months
      resulted in significant improvement of QL, however combination AHT provided
      significantly better estimates of QL. CONCLUSION: In patients with AH and anxiety
      or depressive disorders effectiveness of AHT combined with anxiolytic or
      antidepressant was higher compared with isolated AHT.

PMID- 29041881
TI  - [Age-Related Changes of Heart Rate Variability at Various Insulin Sensitivity and
      Telomere Length].
AB  - AIM: To study relationship between age-associated changes of heart rate
      variability (HRV), telomere length (TL), and lowering of insulin sensitivity
      (IS). MATERIAL AND METHODS: We included in this study 229 individuals aged 23-91
      years without clinical manifestations of cardiovascular and other somatic
      diseases. In all participants, we analyzed HRV parameters obtained at 24-hour ECG
      monitoring (24-h ECG) and 5 minutes ECG recordings in the supine and standing
      positions. Leukocyte TL was estimated on genomic DNA using real time polymerase
      chain reaction. Insulin sensitivity was characterized by calculation of NOMA-IR
      and Gutt's insulin sensitivity index (ISI). RESULTS: Elderly people with short
      telomeres (.

PMID- 29041882
TI  - [Specific Characteristics of Coronary Atherosclerosis].
AB  - In this review, we present modern aspects of etiology and pathogenesis of
      atherosclerosis. We describe the roles played by inflammatory cells, components
      of cellular response in allergic reactions, disturbances of carbohydrate
      metabolism, cellular aging, and infection at various stages of formation of
      atherosclerotic plaques. Special attention is given to the specific
      characteristics of atherosclerosis and calcification of coronary arteries. We
      show the influence of age and gender on the disease progression. The review
      includes information on the importance of myocardial bridges for the change of
      hemodynamics in segments of coronary arteries. The data presented indicate that
      differences in localization of atherosclerotic lesions between systems of the
      right and left coronary arteries depends on their hemodynamic, anatomical and
      physiological characteristics. According to the literature, anterior descending
      artery is more vulnerable in this respect.

PMID- 29041883
TI  - [Molecular Aspects of Translational Cardiology in Vascular Wall Research].
AB  - Clinical-biochemical research of vascular wall hydrated state, water-electrolyte
      balance has broadened substantially our notions concerning initiation mechanism
      of vessel damages, methods of their prevention and treatment. Consecutive study
      of endothelial glycocalyx functioning, computational research of its interaction
      with oxidative stress, regulation of its state has been aimed at development of
      novel means of the vascular system protection. Mutual efforts of clinicians and
      scientists should contribute to the productivity of results of translational
      cardiology.

PMID- 29041884
TI  - [Syndrome Takotsubo: the Value of Echocardiography].
AB  - Analysis of diagnostic and prognostic possibilities of echocardiography in
      patients with Takotsubo syndrome is given in this review. Special characteristics
      of local wall motion abnormalities of the left ventricle are presented and main
      variants of transitory derangements of local contractility are described. Changes
      of parameters of deformation of left and right ventricles in acute period and
      during follow-up are analyzed in detail. A spectrum of complications of the
      syndrome in detection of which echocardiography plays the leading role is
      outlined. The review also contains analysis of prognostically unfavorable states
      and echocardiographic parameters specific for Takotsubo syndrome.

PMID- 29041885
TI  - [Review of Novel Clinical Recommendations on Diagnosis and Treatment of Atrial
      Fibrillation (2016) of the European Society of Cardiology Developed in
      Collaboration With the European Association for Car dio-Thor acic Surgery].

PMID- 29041886
TI  - [Polymorphisms in Genes of Cytokines and Matrix Metalloproteinases Associated
      With Ischemic Heart Disease in Patients With Type 2 Diabetes].
AB  - OBJECTIVE: To examine associations between ischemic heart disease (IHD) and
      polymorphisms in cytokine genes (IL-1B, IL-4, IL-6, IL-10, TNFA, VEGF) and matrix
      metalloproteinase genes (MMP2, MMP3, MMP9) in patients with type 2 diabetes.
      MATERIAL AND METHODS: We studied 232 Caucasian diabetic subjects (33 men and 199
      women aged 50-70 years). In 93 patients IHD was verified by treadmill test and/or
      coronary angiography (86 subjects with stable angina, 19 with previous myocardial
      infarction). Thirteen polymorphisms localized in the promoters of IL-1B
      (rs1143627), IL-4 (rs2243250), IL-6 (rs1800795), IL-10 (rs1800872, rs1800896),
      TNFA (rs361525, rs1800629, rs1800630), VEGF (rs699947, rs3025039), MMP2
      (rs243865), MMP3 (rs3025058) and MMP9 (rs3918242) were investigated. RESULTS:
      Prevalence of G-allele and GG-genotype at -308 position of TNFA (rs1800629), as
      well as C-allele and CC-genotype at position +936 of VEGF (rs3025039) was higher
      in patients with IHD as compared to patients without IHD (OR=2.0, OR=2.2, OR=2.1,
      OR=2.4, respectively, all p=0.02). In logistic regression analysis, TNFA -308 A/G
      and VEGF +936 C/T polymorphisms showed associations with IHD (both p=0.009).
      These polymorphisms along with age, body mass index, duration of diabetes, low
      density and high density lipoprotein cholesterol were associated with IHD in
      multivariate models (p=0.0002 and p=0.00008, respectively). Nine combinations of
      TNFA -308 GG-genotype and variants of other genes demonstrated associations with
      IHD (p<=0.002). CONCLUSION: The polymorphisms in promoter regions of TNFA
      (rs1800629) and VEGF (rs3025039) are associated with IHD in patients with type 2
      diabetes.

PMID- 29041887
TI  - [Comparison of Diagnostic Values of Instantaneous Wave-Free R atio and Fractional
      Flow R eserve With Noninvasive Methods for Evaluating Myocardial Ischemia in
      Assessment of the Functional Significance of Intermediate Coronary Stenoses in
      Patients With Chronic Ischemic Heart Disease].
AB  - OBJECTIVE: To compare the diagnostic accuracy of instantaneous wave-free ratio
      (iFR) and fractional flow reserve (FFR) with noninvasive methods in assessment of
      the functional significance of moderate coronary stenoses in patients with
      chronic ischemic heart disease (IHD). METHODS: We included in this study 50
      patients with chronic or suspected IHD and moderate coronary stenoses (50-70%; 74
      stenoses). Values of iFR and FFR were determined within 10 days after noninvasive
      stress tests (combination of stress-echo and SPECT). The values of iFR and FFR
      were compared with the results of noninvasive methods by ROC-analysis. Coronary
      artery stenosis was considered functionally important if at least one of
      noninvasive tests (stress-echo or SPECT) demonstrated positive result. RESULTS:
      The results of noninvasive stress-tests were positive in 14 patients (28%). ROC
      area under the curve (AUC) for iFR - 0.961+/-0.019 (95%CI 0.888-0.992). The best
      cut-off point for iFR is 0.92 (sensitivity 100, specificity 84%). ROC AUC for FFR
      - 0.893+/-0.041 (95%CI 0.79-0.96). The best cut-off point for FFR is 0.81
      (sensitivity 100% and specificity 69%). There was no significant difference
      between iFR and FFR ROC-curves (r=0.0845). CONCLUSION: The values of iFR and FFR
      have equivalent agreement with the results of noninvasive tests commonly used to
      detect myocardial ischemia in patients with moderate coronary stenoses.

PMID- 29041888
TI  - [Diffusion Capacity of the Lung and Maladaptive Post-Infarction Remodeling of the
      Heart].
AB  - OBJECTIVE: To assess the association of the lowering of diffusion capacity of the
      lung and maladaptive remodeling of the heart in a year after myocardial
      infarction (MI). MATERIALS AND METHODS: We included into this study 107 patients
      with ST elevation MI (STEMI). Examination of all patients on 7-12 th days
      included echocardiography (echoCG), spirography, body plethysmography, and
      determination of lung diffusion capacity. After one year of observation in 87
      patients (81.3%) we performed echocardiogram in dynamics. RESULTS: After 1 year
      signs of maladaptive remodeling were detected in 25 patients (28.7%). The group
      of patients with remodeling had clinically significantly lowered parameters of
      lung diffusion function: diffusion capacity corrected for hemoglobin (DLCOcor) by
      30% (p=0.001) and diffusing capacity for carbon monoxide/alveolar volume (DL/VA)
      by 21% (p=0.001). A mathematical model for prediction of maladaptive cardiac
      remodeling was obtained by the method of multivariate discriminant analysis.
      Univariate analysis showed that the reduction of DLCOcor was associated with 3.5
      fold elevation of the risk of maladaptive remodeling in one year after STEMI.
      After adjustment for risk factors this risk rose up to 13.7-fold. CONCLUSION:
      Reduction of lung diffusion capacity below 80% of the predicted value on the 12
      th day of STEMI was associated with 13.7-fold increase of the risk of detection
      of maladaptive remodeling of the heart after one year. Independent predictors of
      cardiac maladaptive remodeling were the number of diseased coronary arteries,
      reduced DLCO and the presence of myocardial remodeling during acute phases of
      myocardial infarction.

PMID- 29041889
TI  - [Multifactorial Prognostication of Remote Outcomes in Patients With Non-ST
      Elevation Acute Coronary Syndrome].
AB  - AIM: Creation of a mathematical nonlinear regression model for prognostication of
      1 year outcomes after non-ST elevation acute coronary syndrome (NSTE ACS) for
      optimization of rehabilitation, secondary prevention, and personalized approach
      to treatment. MATERIAL AND METHODS: We included in this study 135 patients with
      confirmed NSTE ACS (mean age 59.1+/-6.1 years, 94 men and 41 women) admitted to
      hospital No 1 in Novosibirsk during 2010. During hospitalization and 1 year after
      discharge these patients received standard medical therapy. All patients
      underwent clinical and instrumental examination which included
      electrocardiography, echocardiography, Holter ECG monitoring. Program of clinical
      investigation also included determination of levels of inflammatory cytokines and
      molecular genetic studies. Effect of each of studied parameters on the
      probability of unfavorable one year prognosis was assessed by methods of
      correlation and factor analysis. RESULTS: The constructed mathematical model of
      multifactor prognostication of 1 year unfavorable or favorable outcomes after
      NSTE ACS included patient's age in years, presence of tachycardia at admission,
      Killip class >II, life-threatening paroxysmal tachyarrhythmias, as well as serum
      concentration of high-sensitivity C-reactive protein and CT genotype of a
      polymorphic variant rs1376251 of TAS2R50 gene. CONCLUSION: The use of the
      proposed model of multivariate prognostication of 1 year outcomes of NSTE ACS
      allows to improve the accuracy of events prediction, as it is based on data from
      Russian patients and takes into account the activity of subclinical inflammation
      and genotype of the patient. The model is simple to use and allows to personalize
      secondary prevention, which will facilitate lowering of total cardiovascular risk
      in these patients.

PMID- 29041891
TI  - [Functional State of Vascular Endothelium in Patients With Pulmonary Arterial
      Hypertension Associated With Congenital Heart Diseases].
AB  - In this article, we present results of the study of blebbing activity of
      membranes of peripheral blood lymphocytes, concentrations of soluble
      platelet/endothelial cell adhesion molecule 1, and vascular endothelial growth
      factor (VEGF) in patients with pulmonary arterial hypertension associated with
      congenital heart diseases. The research has shown that hypoxia and hemodynamic
      factors are the initiators of blebbing of membrane of peripheral blood
      lymphocytes. The activity of blebbing increases in parallel with the severity of
      the disease. Aberrant leukocyte-endothelial interactions lead to the breach of
      athrombogenic endothelium function, hypercoagulation and risk of thrombosis.
      Revealed overexpression of VEGF, aimed at restoration of endothelial cells, has
      been most pronounced in cyanotic congenital heart defects. We suggest that the
      potentiating effect of apoptosis and endothelial cells' proliferation is a key
      factor of irreversibility of pulmonary arterial hypertension in congenital heart
      defects.

PMID- 29041892
TI  - [Randomized Controlled Trials in Patients With Heart Failure in Russia Following
      the Study Topcat: What Awaits us in the Future].

PMID- 29041890
TI  - [Effect of Cholecalciferol and Diuretics as Components of Combination
      Antihypertensive Therapy on Plasma Renin Activity and Endothelial Function in
      Patients With Arterial Hypertension].
AB  - AIM: To evaluate the effect of cholecalciferol and diuretics as components of
      combination antihypertensive therapy (CAHT) on plasma renin activity (PRA) and
      endothelial function in patients with arterial hypertension (AH). MATERIALS AND
      METHODS: We included in this prospective study 153 patients with II-degree AH.
      Duration of follow-up was 15.8+/-1.8 months. Patients were divided into four
      groups: patients of group 0 received CAHT without cholecalciferol or diuretic; of
      group 1 - CAHT with cholecalciferol (2000 IU daily); of group 2 - CAHT with
      diuretic; of group 3 - CAHT with diuretic and cholecalciferol 2000 IU daily.
      RESULTS: After treatment, the highest level of 25-hydroxy vitamin D (25(OH)D)
      (48.9 [34.3; 67.9] ng/ml) and its greatest dynamics (Delta) - (27.5 [6.2; 48.8]
      ng/mL) were observed in group 1. With diuretics blood level of 25(OH)D and its
      Delta were lower (p.

PMID- 29041893
TI  - [Transcatheter Implantation of Mitral Valve Prostheses: Current Status of the
      Problem].
AB  - Mitral valve disease is highly prevalent and quickly leads to development of
      severe heart failure. Mitral valve disease of degenerative or ischemic etiology
      affects 7.5 and 9.3% of population older than 65 and 75 years, respectively.
      "Open" (with cardiopulmonary bypass) surgical repair or valve replacement are not
      possible in almost half of affected patients because of their complications and
      concomitant diseases responsible for extremely high risk of these interventions.
      In the last decade, minimally invasive endovascular technology - transcatheter
      aortic valve implantation (TAVI) - has been widely introduced for correction of
      aortic valve disease in similar category of patients. However, transcatheter
      mitral valve implantation (TMVI) has been developed just during recent couple of
      years.

PMID- 29041894
TI  - [Clinical Features of Arterial Hypertension in the Elderly and Senile Age and the
      Rationale for Using the Combination of Amlodipine/Indapamide-retard].
AB  - The proportion of elderly in the population is growing. The two-thirds of those
      over the age of 65 has arterial hypertension (AH). There is a significant
      increase in the incidence of isolated systolic hypertension with age. The
      relationship between increased pulse pressure, arterial stiffness and aging
      processes has been repeatedly confirmed in population epidemiological studies.
      Some evidence has been found that the treatment of AH in the elderly is
      accompanied by a reduction in the risk of cardiovascular diseases. Target levels
      of blood pressure (BP) in elderly people with AH younger than 80 years, as well
      as over 80 years with a satisfactory physical and cognitive status with systolic
      BP >=160 mm Hg is recommended to be reduce to 140-150 mm Hg. Low doses of
      thiazide diuretics and long-acting calcium channels blockers (mainly
      dihydropyridine) are attributed to first-line drugs in order to effectively
      reduce cardiovascular complications in the treatment of AH in the elderly. Their
      prescription as a fixed-dose combination appears to be an optimal solution when
      monotherapy is fails.

PMID- 29041895
TI  - [Actual Issues of Choosing Anticoagulant Therapy for Long-term Prophylaxis of
      Thromboembolic Complications].
AB  - The article contains presentation of actual problems of selection of
      anticoagulant therapy for long term prevention of thromboembolic complications in
      outpatients with atrial fibrillation, chronic heart failure, and chronic kidney
      disease.tions in ambulatory Patients with atrial fibrillation, chronic heart
      failure and chronic kidney disease.

PMID- 29041896
TI  - [Recommendations of the Society of Specialists in Urgent Cardiology Diagnosis and
      Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome. Part
      1].

PMID- 29041897
TI  - Small molecule modulation of splicing factor expression is associated with rescue
      from cellular senescence.
AB  - BACKGROUND: Altered expression of mRNA splicing factors occurs with ageing in
      vivo and is thought to be an ageing mechanism. The accumulation of senescent
      cells also occurs in vivo with advancing age and causes much degenerative age
      related pathology. However, the relationship between these two processes is
      opaque. Accordingly we developed a novel panel of small molecules based on
      resveratrol, previously suggested to alter mRNA splicing, to determine whether
      altered splicing factor expression had potential to influence features of
      replicative senescence. RESULTS: Treatment with resveralogues was associated with
      altered splicing factor expression and rescue of multiple features of senescence.
      This rescue was independent of cell cycle traverse and also independent of SIRT1,
      SASP modulation or senolysis. Under growth permissive conditions, cells
      demonstrating restored splicing factor expression also demonstrated increased
      telomere length, re-entered cell cycle and resumed proliferation. These phenomena
      were also influenced by ERK antagonists and agonists. CONCLUSIONS: This is the
      first demonstration that moderation of splicing factor levels is associated with
      reversal of cellular senescence in human primary fibroblasts. Small molecule
      modulators of such targets may therefore represent promising novel anti
      degenerative therapies.

PMID- 29041898
TI  - Societal preferences for adjuvant melanoma health states: UK and Australia.
AB  - BACKGROUND: No studies have measured preference-based utility weights for
      specific toxicities and outcomes associated with approved and investigational
      adjuvant treatments for patients with resected high-risk melanoma. METHODS: A
      cross-sectional study was conducted in the United Kingdom and Australia to obtain
      utilities for 14 adjuvant melanoma health states. One-on-one interviews were
      conducted using standard gamble; utility weights range from 0.0, dead, to 1.0,
      full health. Supplemental risk questions also were asked. RESULTS: Among 155
      participants (52% male; mean age, 46 years) "adjuvant treatment no toxicities"
      (0.89) was most preferred, followed by "induction treatment" (0.88), and "no
      treatment" (0.86). Participants least preferred "cancer recurrence" (0.62); the
      utility for "cancer recurrence and 10-year survival with treatment" was 0.70.
      Disutilities for grade 2 toxicities ranged from -0.06 for fatigue to -0.13 for
      hypophysitis. The mean maximum acceptable risk of a life-threatening event ranged
      from 30% for a 6% increase in the chance of remaining cancer free over 3 years to
      40% for an 18% increase; Australian respondents were willing to take higher
      risks. CONCLUSION: Reproducible health utilities for adjuvant melanoma health
      states were obtained from the general population in two countries. These
      utilities can be incorporated into treatment-specific cost-effectiveness
      evaluations.

PMID- 29041899
TI  - How effective are family-based and institutional nutrition interventions in
      improving children's diet and health? A systematic review.
AB  - BACKGROUND: Effective strategies to improve dietary intake in young children are
      a priority to reduce the high prevalence of chronic non-communicable diseases in
      adulthood. This study aimed to assess the impact of family-based and
      school/preschool nutrition programs on the health of children aged 12 or younger,
      including the sustainability of these impacts and the relevance to socio-economic
      inequalities. METHODS: A systematic review of literature published from 1980 to
      December 2014 was undertaken. Randomised controlled trials involving families
      with children aged up to 12 years in high income countries were included. The
      primary outcomes were dietary intake and health status. Results were presented in
      a narrative synthesis due to the heterogeneity of the interventions and outcomes.
      RESULTS: The systematic search and assessment identified 39 eligible studies. 82%
      of these studies were set in school/preschools. Only one school study assessed
      the impact of involving parents systematically. The family-based programs which
      provided simple positive dietary advice to parents and regular follow-up reduced
      fat intake significantly. School and family-based studies, if designed and
      implemented well, increased F&V intake, particularly fruit. Effective school
      based programs have incorporated role-models including peers, teachers and heroic
      figures, rewards and increased access to healthy foods. School nutrition programs
      in disadvantaged communities were as effective as programs in other communities.
      CONCLUSIONS: Family and school nutrition programs can improve dietary intake,
      however evidence of the long-term sustainability of these impacts is limited. The
      modest overall impact of even these successful programs suggest complementary
      nutrition interventions are needed to build a supportive environment for healthy
      eating generally.

PMID- 29041900
TI  - Mutual maintenance of di- and triploid Pelophylax esculentus hybrids in R-E
      systems: results from artificial crossings experiments.
AB  - BACKGROUND: Interspecies animal hybrids can employ clonal or hemiclonal
      reproduction modes where one or all parental genomes are transmitted to the
      progeny without recombination. Nevertheless, some interspecies hybrids retain
      strong connection with the parental species needed for successful reproduction.
      Appearance of polyploid hybrid animals may play an important role in the
      substitution of parental species and in the speciation process. RESULTS: To
      establish the mechanisms that enable parental species, diploid and polyploid
      hybrids coexist we have performed artificial crossing experiments of water frogs
      of Pelophylax esculentus complex. We identified tadpole karyotypes and oocyte
      genome composition in all females involved in the crossings. The majority of
      diploid and triploid hybrid frogs produced oocytes with 13 bivalents leading to
      haploid gametes with the same genome as parental species hybrids usually coexist
      with. After fertilization of such gametes only diploid animals appeared. Oocytes
      with 26 bivalents produced by some diploid hybrid frogs lead to diploid gametes,
      which give rise to triploid hybrids after fertilization. In gonads of all diploid
      and triploid hybrid tadpoles we found DAPI-positive micronuclei (nucleus-like
      bodies) involved in selective genome elimination. Hybrid male and female
      individuals produced tadpoles with variable karyotype and ploidy even in one
      crossing owing to gametes with various genome composition. CONCLUSIONS: We
      propose a model of diploid and triploid hybrid frog reproduction in R-E
      population systems. Triploid Pelophylax esculentus hybrids can transmit genome of
      parental species they coexist with by producing haploid gametes with the same
      genome composition. Triploid hybrids cannot produce triploid individuals after
      crossings with each other and depend on diploid hybrid females producing diploid
      eggs. In contrast to other population systems, the majority of diploid and
      triploid hybrid females unexpectedly produced gametes with the same genome as
      parental species hybrids coexist with.

PMID- 29041901
TI  - Prevalence of drug-resistant pulmonary tuberculosis in India: systematic review
      and meta-analysis.
AB  - BACKGROUND: Drug-resistant pulmonary tuberculosis (DR-TB) is a significant public
      health issue that considerably deters the ongoing TB control efforts in India.
      The purpose of this review was to investigate the prevalence of DR-TB and
      understand the regional variation in resistance pattern across India from 1995 to
      2015, based on a large body of published epidemiological studies. METHODS: A
      systematic review of published studies reporting prevalence of DR-TB from
      biomedical databases (PubMed and IndMed) was conducted. Meta-analysis was
      performed using random effects model and the pooled prevalence estimate (95%
      confidence interval [CI]) of DR-TB, multidrug resistant (MDR-) TB, pre
      extensively drug-resistant (pre-XDR) TB and XDR-TB were calculated across two
      study periods (decade 1: 1995 to 2005; decade 2: 2006 to 2015), countrywide and
      in different regions. Heterogeneity in this meta-analysis was assessed using I2
      statistic. RESULTS: A total of 75 of 635 screened studies that fulfilled the
      inclusion criteria were selected. Over 40% of 45,076 isolates suspected for
      resistance to any first-line anti-TB drugs tested positive. Comparative analysis
      revealed a worsening trend in DR-TB between the two study decades (decade 1:
      37.7% [95% CI = 29.0; 46.4], n = 25 vs decade 2: 46.1% [95% CI = 39.0; 53.2], n =
      36). The pooled estimate of MDR-TB resistance was higher in previously treated
      patients (decade 1: 29.8% [95% CI = 20.7; 39.0], n = 13; decade 2: 35.8% [95% CI
      = 29.2; 42.4], n = 24) as compared with the newly diagnosed cases (decade 1: 4.1%
      [95% CI = 2.7; 5.6], n = 13; decade 2: 5.6% [95% CI = 3.8; 7.4], n = 17).
      Overall, studies from Western states of India reported highest prevalence of DR
      TB (57.8% [95% CI = 37.4; 78.2], n = 6) and MDR-TB (39.9% [95% CI = 21.7; 58.0],
      n = 6) during decade 2. Prevalence of pre-XDR TB was 7.9% (95% CI = 4.4; 11.4, n
      = 5) with resistance to fluoroquinolone (66.3% [95% CI = 58.2; 74.4], n = 5)
      being the highest. The prevalence of XDR-TB was 1.9% (95% CI = 1.2; 2.6, n = 14)
      over the 20-year period. CONCLUSION: The alarming increase in the trend of anti
      TB drug resistance in India warrants the need for a structured nationwide
      surveillance to assist the National TB Control Program in strengthening treatment
      strategies for improved outcomes.

PMID- 29041902
TI  - An analysis of 67 RNA-seq datasets from various tissues at different stages of a
      model insect, Manduca sexta.
AB  - BACKGROUND: Manduca sexta is a large lepidopteran insect widely used as a model
      to study biochemistry of insect physiological processes. As a part of its genome
      project, over 50 cDNA libraries have been analyzed to profile gene expression in
      different tissues and life stages. While the RNA-seq data were used to study
      genes related to cuticle structure, chitin metabolism and immunity, a vast amount
      of the information has not yet been mined for understanding the basic molecular
      biology of this model insect. In fact, the basic features of these data, such as
      composition of the RNA-seq reads and lists of library-correlated genes, are
      unclear. From an extended view of all insects, clear-cut tempospatial expression
      data are rarely seen in the largest group of animals including Drosophila and
      mosquitoes, mainly due to their small sizes. RESULTS: We obtained the
      transcriptome data, analyzed the raw reads in relation to the assembled genome,
      and generated heatmaps for clustered genes. Library characteristics (tissues,
      stages), number of mapped bases, and sequencing methods affected the observed
      percentages of genome transcription. While up to 40% of the reads were not mapped
      to the genome in the initial Cufflinks gene modeling, we identified the causes
      for the mapping failure and reduced the number of non-mappable reads to <8%.
      Similarities between libraries, measured based on library-correlated genes,
      clearly identified differences among tissues or life stages. We calculated gene
      expression levels, analyzed the most abundantly expressed genes in the libraries.
      Furthermore, we analyzed tissue-specific gene expression and identified 18 groups
      of genes with distinct expression patterns. CONCLUSION: We performed a thorough
      analysis of the 67 RNA-seq datasets to characterize new genomic features of M.
      sexta. Integrated knowledge of gene functions and expression features will
      facilitate future functional studies in this biochemical model insect.

PMID- 29041903
TI  - Imputation of missing genotypes within LD-blocks relying on the basic coalescent
      and beyond: consideration of population growth and structure.
AB  - BACKGROUND: Genotypes not directly measured in genetic studies are often imputed
      to improve statistical power and to increase mapping resolution. The accuracy of
      standard imputation techniques strongly depends on the similarity of linkage
      disequilibrium (LD) patterns in the study and reference populations. Here we
      develop a novel approach for genotype imputation in low-recombination regions
      that relies on the coalescent and permits to explicitly account for population
      demographic factors. To test the new method, study and reference haplotypes were
      simulated and gene trees were inferred under the basic coalescent and also
      considering population growth and structure. The reference haplotypes that first
      coalesced with study haplotypes were used as templates for genotype imputation.
      Computer simulations were complemented with the analysis of real data. Genotype
      concordance rates were used to compare the accuracies of coalescent-based and
      standard (IMPUTE2) imputation. RESULTS: Simulations revealed that, in LD-blocks,
      imputation accuracy relying on the basic coalescent was higher and less variable
      than with IMPUTE2. Explicit consideration of population growth and structure,
      even if present, did not practically improve accuracy. The advantage of
      coalescent-based over standard imputation increased with the minor allele
      frequency and it decreased with population stratification. Results based on real
      data indicated that, even in low-recombination regions, further research is
      needed to incorporate recombination in coalescence inference, in particular for
      studies with genetically diverse and admixed individuals. CONCLUSIONS: To exploit
      the full potential of coalescent-based methods for the imputation of missing
      genotypes in genetic studies, further methodological research is needed to reduce
      computer time, to take into account recombination, and to implement these methods
      in user-friendly computer programs. Here we provide reproducible code which takes
      advantage of publicly available software to facilitate further developments in
      the field.

PMID- 29041904
TI  - Shift in the function of netrin-1 from axon outgrowth to axon branching in
      developing cerebral cortical neurons.
AB  - BACKGROUND: Netrin-1, a multifunctional axon guidance cue, elicits axon outgrowth
      via one of its receptors deleted in colorectal cancer (DCC) in several types of
      neurons, including cerebral cortical neurons of embryonic mice. However, we and
      others have observed de novo formation of axon branches without axon outgrowth
      induced by netrin-1 in cortical culture of neonatal hamsters. These previous
      reports suggested the possibility that netrin-1 function might alter during
      development, which we here investigated using dissociated culture prepared from
      cerebral cortices of embryonic mice. RESULTS: Imaging analysis revealed netrin-1
      induced outgrowth in embryonic day (E) 14 axons and netrin-1-induced branching in
      E16 axons. Netrin-1-evoked filopodial protrusions, which sprouted on the shafts
      of E16 axons preceding branch formation, were visualized by a novel method called
      atmospheric scanning electron microscopy. Treatment with an anti-DCC function
      blocking antibody affected both axon outgrowth and branching. CONCLUSIONS:
      Morphological analyses suggested a possibility of a shift in the function of
      netrin-1 in cortical axons during development, from promotion of outgrowth to
      promotion of branch formation starting with filopodial protrusion. Function
      blocking experiments suggested that DCC may contribute not only to axon outgrowth
      but branching.

PMID- 29041905
TI  - Clinicopathological and prognostic significance of programmed death ligand-1
      expression in breast cancer: a meta-analysis.
AB  - BACKGROUND: Programmed cell death-ligand 1 (PD-L1) may be a useful molecule for
      targeted immunotherapy. Therefore, this meta-analysis aimed to investigate PD-L1
      expression in breast cancer and its associations with clinicopathological factors
      and outcomes, which may help determine whether PD-L1 expression is a useful
      prognostic marker. METHODS: The Medline Ovid, Cochrane, PubMed, Google Scholar,
      and Web of Knowledge databases were searched for studies that evaluated the
      prognostic or clinicopathological significance of PD-L1 expression in patients
      with breast cancer, and reported at least one survival-related outcome. RESULTS:
      Six studies that included 7877 cases were selected for the analysis. Higher PD-L1
      expression in all cells was related to higher histological grade and lymph node
      metastasis. Higher PD-L1 expression in tumor cell was related to larger tumor
      size, estrogen receptor negativity, progesterone receptor negativity, human
      epidermal growth factor type-2 positivity, and triple-negative breast cancer. PD
      L1 positivity in all cells was associated with poorer disease-free survival,
      although it was not significantly associated with overall survival. CONCLUSION:
      The present meta-analysis revealed that cases of breast cancer with PD-L1
      positivity in all cells exhibited higher histological grades, lymph node
      metastasis, and poorer disease-free survival. Therefore, positive expression of
      PD-L1 may be a useful prognostic marker in breast cancer.

PMID- 29041906
TI  - From provocation to aggression: the neural network.
AB  - BACKGROUND: In-vivo observations of neural processes during human aggressive
      behavior are difficult to obtain, limiting the number of studies in this area. To
      address this gap, the present study implemented a social reactive aggression
      paradigm in 29 healthy men, employing non-violent provocation in a two-player
      game to elicit aggressive behavior in fMRI settings. RESULTS: Participants
      responded more aggressively after high provocation reflected in taking more money
      from their opponents. Comparing aggression trials after high provocation to those
      after low provocation revealed activations in neural circuits involved in
      aggression: the medial prefrontal cortex (mPFC), the orbitofrontal cortex (OFC),
      the dorsolateral prefrontal cortex (dlPFC), the anterior cingulate cortex (ACC),
      and the insula. In general, our findings indicate that aggressive behavior
      activates a complex, widespread brain network, reflecting a cortico-limbic
      interaction and overlapping with circuits underlying negative emotions and
      conflicting decision-making. Brain activation during provocation in the OFC was
      associated with the degree of aggressive behavior in this task. CONCLUSION:
      Therefore, data suggest there is greater susceptibility for provocation, rather
      than less inhibition of aggressive tendencies, in individuals with higher
      aggressive responses. This further supports the hypothesis that reactive
      aggression can be seen as a consequence of provocation of aggressive emotional
      responses and parallel evaluative regulatory processes mediated mainly by the
      insula and prefrontal areas (OFC, mPFC, dlPFC, and ACC) respectively.

PMID- 29041907
TI  - Detection of bacterial DNA by in situ hybridization in patients with
      decompensated liver cirrhosis.
AB  - BACKGROUND: Spontaneous bacterial peritonitis (SBP) is often difficult to
      diagnose because bacteria in ascites cannot be detected accurately by
      conventional culture. In situ hybridization (ISH) was previously developed for
      rapid detection of genes from bacteria phagocytized by neutrophils. SBP may
      develop after bacteria enter into the systemic circulation following bacterial
      translocation. Therefore, we performed ISH to identify bacteria in blood samples
      collected from patients with decompensated liver cirrhosis (LC). METHODS: In this
      retrospective study, peripheral blood samples were collected from 60 patients
      with decompensated LC, and bacteria were detected by both blood culture and ISH.
      Moreover, 35 patients underwent paracentesis for diagnosis of SBP. RESULTS: Eight
      of 35 patients were diagnosed with SBP by polymorphonuclear neutrophil counts,
      and one patient was diagnosed with bacterascites. Seven of the nine patients
      showed positive results for ISH, whereas bacteria were detected in only two cases
      by blood culture. Thirty-seven of 60 cases (62%) showed positive results for ISH,
      whereas only six samples (10%) were positive by blood culture analysis. Compared
      with the 23 cases of negative ISH, the 37 cases of positive ISH showed a higher
      frequency of fever, higher Child-Pugh scores, and lower albumin levels.
      CONCLUSIONS: Detection of bacteria by ISH suggested that bacterial translocation,
      which cannot be proven by conventional culture, occurred in these patients, and
      that ISH could be helpful for the early diagnosis of some types of infection and
      prevention of SBP in these patients.

PMID- 29041908
TI  - A qualitative study of employees' opinions on establishing a generic call-centre.
AB  - BACKGROUND: To investigate opinions among employees at an Out-of-Hours general
      practitioner (OOH-GP) service and a safety alarm service about the establishment
      of a generic call-centre. METHODS: Qualitative study using individual and group
      interviews with 14 employees and managers involved in preparation of a merge into
      a new generic call-centre. They were asked about their opinions towards
      establishing a generic call-centre where all contact about unplanned health
      inquiries from the public had to be done by telephone and how to solve more
      requests on the phone. Data was analysed thematically. RESULTS: Participants who
      alternate between call handling and direct patient contact (personnel at the OOH
      GP) believed that just handling calls would be monotonous, less challenging and
      provide poorer quality. This was not supported by those working at the safety
      alarm service. There were different opinions about introducing mandatory use of
      decision support system for all inquiries, but it was a common understanding that
      it would lead to more patients in need of face-to-face consultations due to over
      triage. To solve more requests on the phone participants believed a public
      information campaign was required, that GPs received more of the emergency
      requests within their ordinary working hours and having salaried doctors in the
      OOH-GP service. CONCLUSION: In the participants' opinion, successful
      establishment of a generic call-centre depends on the employees' possibility of
      direct patient contact, clarifications on the use of decision support system and
      good information to the population.

PMID- 29041909
TI  - Cost-utility analysis of Palivizumab for Respiratory Syncytial Virus infection
      prophylaxis in preterm infants: update based on the clinical evidence in Spain.
AB  - BACKGROUND: This study aimed at estimating the efficiency of palivizumab in the
      prevention of Respiratory Syncytial Virus (RSV) infection and its sequelae in
      preterm infants (32day 1-35day 0weeks of gestational age -wGA-) in Spain.
      METHODS: A decision-tree model was developed to compare health benefits (Quality
      Adjusted Life Years-QALYs) and costs of palivizumab versus a non-prophylaxis
      strategy over 6 years. A hypothetical cohort of 1,000 preterm infants, 32day 1
      35day 0 wGA (4.356 kg average weight) at the beginning of the prophylaxis (15
      mg/kg of palivizumab; 3.88 average number of injections per RSV season) was
      analysed. The model considered the most recent evidence from Spanish
      observational and epidemiological studies on RSV infection: the FLIP II study
      provided hospital admission and Intensive Care Unit (ICU) admission rates; in
      hospital mortality rate was drawn from an epidemiological study from 2004 to
      2012; recurrent wheezing rates associated to RSV infection from SPRING study were
      adjusted by the evidence on the palivizumab effect from clinical trials. Quality
      of life baseline value, number of hospitalized infants and the presence of
      recurrent wheezing over time were granted to estimate QALYs. National Health
      Service and societal perspective (included also recurrent wheezing indirect cost)
      were analysed. Total costs (?, 2016) included pharmaceutical and administration
      costs, hospitalization costs and recurrent wheezing management annual costs. A
      discount rate of 3.0% was applied annually for both costs and health outcomes.
      RESULTS: Over 6 years, the base case analysis showed that palivizumab was
      associated to an increase of 0.0731 QALYs compared to non-prophylaxis. Total
      costs were estimated in ?2,110.71 (palivizumab) and ?671.68 (non-prophylaxis)
      from the National Health System (NHS) perspective, resulting in an incremental
      cost utility ratio (ICUR) of ?19,697.69/QALYs gained (prophylaxis vs non
      prophylaxis). Results derived from the risk-factors population subgroups analysed
      were in line with the total population results. From the societal perspective,
      the incremental cost associated to palivizumab decreased to an ?1,253.14 (ICUR =
      ?17,153.16?/QALYs gained for palivizumab vs non-prophylaxis). One-way and
      probabilistic sensitivity analyses confirmed the robustness of the model.
      CONCLUSIONS: The prophylaxis with palivizumab is efficient for preventing from
      RSV infections in preterm infants 32day 1-35day 0 wGA in Spain.

PMID- 29041910
TI  - Takotsubo cardiomyopathy in a patient with ileus: a case report.
AB  - BACKGROUND: Takotsubo cardiomyopathy (TCM) is a form of stress-induced
      cardiomyopathy featured by the dilatation of the apex of the left ventricle
      during systole. Whereas the pathogenesis of this disorder is not well understood,
      it usually occurs after an emotional or physical stress such as acute asthma,
      surgery, chemotherapy, and stroke. However, its occurrence in ileus patients is
      rarely reported. We hereby report probably the first case of TCM after ileus in
      the literature and discuss its implications. CASE PRESENTATION: An 85-year-old
      man was brought to the Emergency Department due to vomiting, abdominal pain, and
      no stool passages for 2 days. His abdomen was markedly distended, and ileus
      pattern was observed in the plain film of abdomen. Electrocardiogram showed right
      axis deviation, poor R-wave progression, and diffuse ST-segment elevation in the
      anterior leads, and cardiomegaly was observed by roentgenogram. A
      ventriculography showed an ejection fraction of 33% and confirmed the apical
      dilation consistent with TCM. He was treated with medication and discharged
      without remarkable adverse events. A follow-up transthoracic echocardiogram 4
      months later showed normalization of his left ventricular systolic functions.
      CONCLUSION: The precise mechanisms of the development of TCM are still unknown,
      but it is widely believed that it is triggered by the catecholamine surge
      produced in response to stress. This case demonstrated that such a stress can be
      of various forms, including ileus and other conditions that may lead to severe
      abdominal pain, and highlight the importance of awareness in diagnosing this rare
      but potentially lethal condition.

PMID- 29041911
TI  - Role of tube size and intranasal compression of the nasotracheal tube in
      respiratory pressure loss during nasotracheal intubation: a laboratory study.
AB  - BACKGROUND: Small nasotracheal tubes (NTTs) and intranasal compression of the NTT
      in the nasal cavity may contribute to increasing airway resistance. Since the
      effects of size, shape, and partial compression of the NTT on airway resistance
      have not been investigated, values of airway resistance with partial compression
      of preformed NTTs of various sizes were determined. METHODS: To determine the
      factors affecting the respiratory pressure loss during the nasotracheal
      intubation, physical and fluid dynamics simulations were used. The internal minor
      axes of NTTs in the nasal cavity of intubated patients were measured using dial
      calipers. In physical and fluid dynamics simulations, pressure losses through the
      tubular parts, compressed parts, and slip joints of NTTs with internal diameters
      (IDs) of 6.0, 6.5, 7.0, 7.5, and 8.0 mm were estimated under partial compression.
      RESULTS: The median internal minor axes of the 7.0- and 7.5-mm ID NTTs in the
      nasal cavity were 5.2 (4.3-5.6) mm and 6.0 (4.2-7.0) mm, respectively. With a
      volumetric air flow rate of 30 L/min, pressure losses through uncompressed NTTs
      with IDs of 6.0-, 6.5-, 7.0-, 7.5- and 8.0-mm were 651.6 +/- 5.7 (6.64 +/- 0.06),
      453.4 +/- 3.9 (4.62 +/- 0.04), 336.5 +/- 2.2 (3.43 +/- 0.02), 225.2 +/- 0.2 (2.30
      +/- 0.00), and 179.0 +/- 1.1 Pa (1.82 +/- 0.01 cmH2O), respectively; the pressure
      losses through the slip joints were 220.3 (2.25), 131.1 (1.33), 86.8 (0.88), 57.1
      (0.58), and 36.1 Pa (0.37 cmH2O), respectively; and the pressure losses through
      the curvature of the NTT were 71.6 (0.73), 69.0 (0.70), 64.8 (0.66), 32.5 (0.33),
      and 41.6 Pa (0.42 cmH2O), respectively. A maximum compression force of 34.1 N
      increased the pressure losses by 82.0 (0.84), 38.0 (0.39), 23.5 (0.24), 16.6
      (0.17), and 9.3 Pa (0.09 cmH2O), respectively. CONCLUSION: Pressure losses
      through NTTs are in inverse proportion to the tubes' IDs; greater pressure losses
      due to slip joints, acute bending, and partial compression of the NTT were
      obvious in small NTTs. Pressure losses through NTTs, especially in small NTTs,
      could increase the work of breathing to a greater extent than that through
      standard tubes; intranasal compression further increases the pressure loss.

PMID- 29041912
TI  - Quality of life questionnaire predicts poor exercise capacity only in HFpEF and
      not in HFrEF.
AB  - BACKGROUND: The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is the
      most widely used measure of quality of life (QoL) in HF patients. This
      prospective study aimed to assess the relationship between QoL and exercise
      capacity in HF patients. METHODS: The study subjects were 118 consecutive
      patients with chronic HF (62 +/- 10 years, 57 females, in NYHA I-III). Patients
      answered a MLHFQ questionnaire in the same day of complete clinical, biochemical
      and echocardiographic assessment. They also underwent a 5 min walk test (6-MWT),
      in the same day, which grouped them into; Group I: <= 300 m and Group II: >300 m.
      In addition, left ventricular (LV) ejection fraction (EF), divided them into:
      Group A, with preserved EF (HFpEF) and Group B with reduced EF (HFrEF). RESULTS:
      The mean MLHFQ total scale score was 48 (+/-17). The total scale, and the
      physical and emotional functional MLHFQ scores did not differ between HFpEF and
      HFpEF. Group I patients were older (p = 0.003), had higher NYHA functional class
      (p = 0.002), faster baseline heart rate (p = 0.006), higher prevalence of smoking
      (p = 0.015), higher global, physical and emotional MLHFQ scores (p < 0.001, for
      all), larger left atrial (LA) diameter (p = 0.001), shorter LV filling time (p =
      0.027), higher E/e' ratio (0.02), shorter isovolumic relaxation time (p = 0.028),
      lower septal a' (p = 0.019) and s' (p = 0.023), compared to Group II. Independent
      predictors of 6-MWT distance for the group as a whole were increased MLHFQ total
      score (p = 0.005), older age (p = 0.035), and diabetes (p = 0.045), in HFpEF were
      total MLHFQ (p = 0.007) and diabetes (p = 0.045) but in HFrEF were only LA
      enlargement (p = 0.005) and age (p = 0.013. A total MLHFQ score of 48.5 had a
      sensitivity of 67% and specificity of 63% (AUC on ROC analysis of 72%) for
      limited exercise performance in HF patients. CONCLUSIONS: Quality of life,
      assessment by MLHFQ, is the best correlate of exercise capacity measured by 6
      MWT, particularly in HFpEF patients. Despite worse ejection fraction in HFrEF,
      signs of raised LA pressure independently determine exercise capacity in these
      patients.

PMID- 29041913
TI  - Detrimental effects of specific Periodontopathic bacterial infection on
      tachyarrhythmia compared to Bradyarrhythmia.
AB  - BACKGROUND: Tachyarrhythmia (TA) and bradyarrhythmia (BA) are cardiac rhythm
      disorders that result in the decline of quality of life. While patients with
      periodontitis are at a high risk of cardiovascular disease (CVD), little causal
      information between TA and BA has been provided to date. To assess the
      relationship, periodontal bacterial infection in patients with TA or BA was
      evaluated. METHODS: The subjects were patients with TA (n = 98) or BA (n = 40)
      who attended Tokyo Medical and Dental University hospital. Periodontal and blood
      examinations were performed. Periodontopathic bacterial existence in saliva was
      evaluated. RESULTS: We found that specific periodontopathic bacteria,
      Porphyromonas gingivalis and Prevotella intermedia, were highly detected in
      saliva from TA patients compared to BA subjects. The rates of hypertension and
      dyslipidemia were comparable between the two groups. CONCLUSION: Specific
      periodontal bacterial infection might affect TA progression.

PMID- 29041915
TI  - Cost-effectiveness analysis of XELOX versus XELOX plus bevacizumab for metastatic
      colorectal cancer in a public hospital school.
AB  - BACKGROUND: Metastatic colorectal cancer imposes a substantial burden on patients
      and society. Over the last years, progresses in the treatment have been made
      especially due to the introduction of monoclonal antibodies, such as bevacizumab
      which, on the other hand, has considerably increased the costs of treatment. We
      performed a cost-effectiveness analysis of bevacizumab plus XELOX in comparison
      with XELOX alone in metastatic colorectal cancer in first-line therapy, from the
      perspective of a public hospital school in Brazil. METHODS: This was a cost
      effectiveness analysis performed by a decision tree and Markov models. Costs were
      expressed in local currency and outcomes were expressed in months of life gained.
      The model was constructed using the TreeAge Pro 2013(r) software. RESULTS: The
      incremental difference in years of life gained was 2.25 months, with an extra
      cost of 47,833.57 BRL, resulting in an incremental cost-effectiveness of
      21,231.43 BRL per month of life gained. CONCLUSIONS: Although the XELOX plus
      bevacizumab regimen is a more expensive and more effective treatment than XELOX,
      it does not fit the reimbursement values fixed by the public healthcare system in
      Brazil.

PMID- 29041914
TI  - Analysis of the genome of the New Zealand giant collembolan (Holacanthella
      duospinosa) sheds light on hexapod evolution.
AB  - BACKGROUND: The New Zealand collembolan genus Holacanthella contains the largest
      species of springtails (Collembola) in the world. Using Illumina technology we
      have sequenced and assembled a draft genome and transcriptome from Holacanthella
      duospinosa (Salmon). We have used this annotated assembly to investigate the
      genetic basis of a range of traits critical to the evolution of the Hexapoda, the
      phylogenetic position of H. duospinosa and potential horizontal gene transfer
      events. RESULTS: Our genome assembly was ~375 Mbp in size with a scaffold N50 of
      ~230 Kbp and sequencing coverage of ~180*. DNA elements, LTRs and simple repeats
      and LINEs formed the largest components and SINEs were very rare. Phylogenomics
      (370,877 amino acids) placed H. duospinosa within the Neanuridae. We recovered
      orthologs of the conserved sex determination genes thought to play a role in sex
      determination. Analysis of CpG content suggested the absence of DNA methylation,
      and consistent with this we were unable to detect orthologs of the DNA
      methyltransferase enzymes. The small subunit rRNA gene contained a possible
      retrotransposon. The Hox gene complex was broken over two scaffolds. For
      chemosensory ability, at least 15 and 18 ionotropic glutamate and gustatory
      receptors were identified, respectively. However, we were unable to identify any
      odorant receptors or their obligate co-receptor Orco. Twenty-three chitinase-like
      genes were identified from the assembly. Members of this multigene family may
      play roles in the digestion of fungal cell walls, a common food source for these
      saproxylic organisms. We also detected 59 and 96 genes that blasted to bacteria
      and fungi, respectively, but were located on scaffolds that otherwise contained
      arthropod genes. CONCLUSIONS: The genome of H. duospinosa contains some unusual
      features including a Hox complex broken over two scaffolds, in a different manner
      to other arthropod species, a lack of odorant receptor genes and an apparent lack
      of environmentally responsive DNA methylation, unlike many other arthropods. Our
      detection of candidate horizontal gene transfer candidates confirms that this
      phenomenon is occurring across Collembola. These findings allow us to narrow down
      the regions of the arthropod phylogeny where key innovations have occurred that
      have facilitated the evolutionary success of Hexapoda.

PMID- 29041916
TI  - Early coordinated rehabilitation in acute phase after hip fracture - a model for
      increased patient participation.
AB  - BACKGROUND: Studies have shown that patients with hip fracture treated in a
      Comprehensive Geriatric Care (CGC) unit report better results in comparison to
      orthopaedic care. Furthermore, involving patients in their healthcare by
      encouraging patient participation can result in better quality of care and
      improved outcomes. To our knowledge no study has been performed comparing
      rehabilitation programmes within a CGC unit during the acute phase after hip
      fracture with focus on improving patients' perceived participation and subsequent
      effect on patients' function. METHODS: A prospective, controlled, intervention
      performed in a CGC unit and compared with standard care. A total of 126 patients
      with hip fracture were recruited who were prior to fracture; community dwelling,
      mobile indoors and independent in personal care. Intervention Group (IG): 63
      patients, mean age 82.0 years and Control Group (CG): 63 patients mean age 80.5
      years. INTERVENTION: coordinated rehabilitation programme with early onset of
      patient participation and intensified occupational therapy and physiotherapy
      after hip fracture surgery. The primary outcome measure was self-reported patient
      participation at discharge. Secondary outcome measures were: TLS-BasicADL; Bergs
      Balance Scale (BBS); Falls Efficacy Scale FES(S); Short Physical Performance
      Battery (SPPB) and Timed Up and Go (TUG) at discharge and 1 month and ADL
      staircase for instrumental ADL at 1 month. RESULTS: At discharge a statistically
      significant greater number of patients in the IG reported higher levels of
      participation (p < 0.05) and independence in lower body hygiene (p < 0.05) and
      dressing (p < 0.001). There were however no statistically significant differences
      at discharge and 1 month between groups in functional balance and confidence,
      performance measures or risk for falls. CONCLUSION: This model of OT and PT
      coordinated inpatient rehabilitation had a positive effect on patients' perceived
      participation in their rehabilitation and ADL at discharge but did not appear to
      affect level of recovery or risk for future falls at 1 month. A large proportion
      of patients remained at risk for future falls at 1 month in both groups
      highlighting the need for continued rehabilitation after discharge. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT03301584 (Retrospectively
      registered: 4th October 2017).

PMID- 29041917
TI  - Locally epistatic models for genome-wide prediction and association by importance
      sampling.
AB  - BACKGROUND: In statistical genetics, an important task involves building
      predictive models of the genotype-phenotype relationship to attribute a
      proportion of the total phenotypic variance to the variation in genotypes. Many
      models have been proposed to incorporate additive genetic effects into prediction
      or association models. Currently, there is a scarcity of models that can
      adequately account for gene by gene or other forms of genetic interactions, and
      there is an increased interest in using marker annotations in genome-wide
      prediction and association analyses. In this paper, we discuss a hybrid modeling
      method which combines parametric mixed modeling and non-parametric rule
      ensembles. RESULTS: This approach gives us a flexible class of models that can be
      used to capture additive, locally epistatic genetic effects, gene-by-background
      interactions and allows us to incorporate one or more annotations into the
      genomic selection or association models. We use benchmark datasets that cover a
      range of organisms and traits in addition to simulated datasets to illustrate the
      strengths of this approach. CONCLUSIONS: In this paper, we describe a new
      strategy for incorporating genetic interactions into genomic prediction and
      association models. This strategy results in accurate models, with sometimes
      significantly higher accuracies than that of a standard additive model.

PMID- 29041918
TI  - The diagnostic value of pepsin detection in saliva for gastro-esophageal reflux
      disease: a preliminary study from China.
AB  - BACKGROUND: None of current diagnostic methods has been proven to be a reliable
      tool for gastro-esophageal reflux disease (GERD). Pepsin in saliva has been
      proposed as a promising diagnostic biomarker for gastro-esophageal reflux. We
      aimed to determine the diagnostic value of salivary pepsin detection for GERD.
      METHODS: Two hundred and fifty patients with symptoms suggestive of GERD and 35
      asymptomatic healthy volunteers provided saliva on morning waking, after lunch
      and dinner for pepsin determination using the Peptest lateral flow device. All
      patients underwent 24-h multichannel intraluminal impedance pH (24-h MII-pH)
      monitoring and upper gastrointestinal endoscopy. Based on 24-h MII-pH and
      endoscopy study, patients were defined as GERD (abnormal MII-pH results and/or
      reflux esophagitis) and non-GERD otherwise. RESULTS: Patients with GERD had a
      higher prevalence of pepsin in saliva and higher pepsin concentration than
      patients with non-GERD and healthy controls (P < 0.001 for all). The pepsin test
      had a sensitivity of 73% and a specificity of 88.3% for diagnosing GERD using the
      optimal cut-off value of 76 ng/mL. Postprandial saliva samples collected when the
      symptoms occurred had a more powerful ability to identify GERD. CONCLUSIONS:
      Salivary pepsin test had moderate diagnostic value for GERD. It may be a
      promising tool to replace the use of currently invasive tools with advantages of
      non-invasive, easy to perform and cost effective. TRIAL REGISTRATION: ChiCTR-DDD
      16009506 (date of registration: October 20, 2016).

PMID- 29041920
TI  - Intraoperative continuous cerebral microcirculation measurement in patients with
      aneurysmal subarachnoid hemorrhage: preliminary data on the early administration
      of magnesium sulfate.
AB  - BACKGROUND: In patients with subarachnoid hemorrhage (SAH), vasospasm remains one
      of the major complications. The application of intravenous magnesium sulfate
      (MgSO4) has been under discussion to prevent cerebral ischemia. Our aim was to
      examine the impact of early MgSO4 administration on local cerebral
      microcirculation during microsurgical clipping of SAH-related aneurysms. METHODS:
      The non-invasive laser-Doppler spectrophotometry system "Oxygen-to-See (O2C)" was
      used in 14 consecutive patients (11 female, 3 male, median age 56.5+/-9.7 yrs)
      with aneurysmatic SAH. A subdural probe measured capillary venous oxygenation
      (SO2), relative hemoglobin content (rHb), blood cell velocity (velo) and blood
      flow (flow) in 7 mm tissue depth. Data samples were recorded as baseline
      immediately before intraoperative application of MgSO4 10% 50 mg/kg body weight
      and 10 min thereafter. The continuous MgSO4 infusion rate depended on blood
      pressure (mean arterial pressure > 60-65 mmHg) and lasted a maximum of 60 min.
      RESULTS: MgSO4 was administered 2.8 (min. 1.6, max. 15.5) hours after onset of
      symptoms. Median flow increased significantly by 20.8% (5-68%, p = 0.001). Velo
      increased 4.9% (1-17%), rHb decreased 1.5% (3-34%) and SO2 decreased 9.4% (8-38%)
      by trend compared to the baseline values. FiO2 correlated positively with velo
      (rs = 0.712, p = 0.004), whereas arterial HCO3 correlated negatively with SO2 (rs
      = -0.599, p = 0.024). Of 14 patients, 2 had symptomatic vasospasm. CONCLUSIONS:
      Our data suggest an increased cerebral blood flow after early intraoperative
      administration of MgSO4 in patients with SAH. Using a non-invasive laser-Doppler
      spectrophotometry system, this technique is feasible for continuous real-time
      monitoring of cerebral microcirculation. TRIAL REGISTRATION: DRKS (German
      Clinical Trial Registry), DRKS00013047 , retrospectively registered on September
      21st, 2017.

PMID- 29041919
TI  - Preparing for the unexpected: special considerations and complications after
      sugammadex administration.
AB  - Sugammadex, a modified gamma-cyclodextrin, has changed clinical practice of
      neuromuscular reversal dramatically. With the introduction of this selective
      relaxant binding agent, rapid and reliable neuromuscular reversal from any depth
      of block became possible. Sugammadex can reverse neuromuscular blockade without
      the muscarinic side effects typically associated with the administration of
      acetylcholinesterase inhibitors. However, what remained unchanged is the
      incidence of residual neuromuscular blockade. It is known that sugammadex cannot
      always prevent its occurrence, if appropriate dosing is not chosen based on the
      level of neuromuscular paralysis prior to administration determined by objective
      neuromuscular monitoring. Alternatively, excessive doses of sugammadex
      administered in an attempt to ensure full and sustained reversal may affect the
      effectiveness of rocuronium in case of immediate reoperation or reintubation. In
      such emergent scenarios that require onset of rapid and reliable neuromuscular
      blockade, the summary of product characteristics (package insert) recommends
      using benzylisoquinolinium neuromuscular blocking agents or a depolarizing agent.
      However, if rapid intubation is required, succinylcholine has a significant
      number of side effects, and benzylisoquinolinium agents may not have the rapid
      onset required. Therefore, prior administration of sugammadex introduces a new
      set of potential problems that require new solutions. This novel reversal agent
      thus presents new challenges and anesthesiologists must familiarize themselves
      with specific issues with its use (e.g., bleeding risk, hypermagnesemia,
      hypothermia). This review will address sugammadex administration in such special
      clinical situations.

PMID- 29041921
TI  - Perioperative management of paraganglioma and catecholamine-induced
      cardiomyopathy in child- a case report and review of the literature.
AB  - BACKGROUND: Paragangliomas are catecholamine-secreting tumors of the paraganglia.
      Perioperative mortality of children with paraganglioma is high, but preoperative
      therapy and anesthetic management of paraganglioma resection are controversial in
      children. The literatures on catecholamine-induced cardiomyopathy are limited to
      several case reports,with few reports of studies on children. CASE PRESENTATION:
      Here we report the anesthetic management of a child with paraganglioma and
      catecholamine-induced cardiomyopathy, and the possible perioperative anesthesia
      problems of the paraganglioma resection are discussed. CONCLUSION: Preoperative
      and intraoperative anesthetic management of Pheochromocytomas children should
      follow the same principles as for adults, The most important aspects are the
      control of blood pressure liability and maintenance of adequate blood volume.
      Pheochromocytomas patient may have cardiomoyopathy due to myocardial toxicity of
      excessive circulating catecholamines level. The perioperative management of
      catecholamine-induced cardiomyopathy should include lowering sympathetic
      activation by means of alpha-and beta-adrenergic receptor blocker and diuretics
      administration in case of volume overload.

PMID- 29041922
TI  - Institute collection and analysis of Nanobodies (iCAN): a comprehensive database
      and analysis platform for nanobodies.
AB  - BACKGROUND: Nanobodies are single-domain antibodies that contain the unique
      structural and functional properties of naturally-occurring heavy chain in
      camelidae. As a novel class of antibody, they show many advantages compared with
      traditional antibodies such as smaller size, higher stability, improved
      specificity, more easily expressed in microorganisms. These unusual hallmarks
      make them as promising tools in basic research and clinical practice. Although
      thousands of nanobodies are known to be published, no single database provides
      searchable, unified annotation and integrative analysis tools for these various
      nanobodies. RESULTS: Here, we present the database of Institute Collection and
      Analysis of Nanobodies (iCAN). It is built for the aim that addressing the above
      gap to expand and accelerate the nanobody research. iCAN, as the first database
      of nanobody, contains the most comprehensive information to date on nanobodies
      and related antigens. So far, iCAN incorporates 2391 entries which include 2131
      from patents and 260 from publications and provides a simple user interface for
      researchers to retrieve and view the detailed information of nanobodies. In
      addition to the data collection, iCAN also provides online bioinformatic tools
      for sequence analysis and characteristic feature extraction. CONCLUSIONS: In
      summary, iCAN enables researchers to analyze nanobody features and explore the
      applications of nanobodies more efficiently. iCAN is freely available at
      http://ican.ils.seu.edu.cn .

PMID- 29041923
TI  - Fetal heart rate abnormalities during and after external cephalic version: Which
      fetuses are at risk and how are they delivered?
AB  - BACKGROUND: Fetal heart rate abnormalities (FHR) during and after external
      cephalic version (ECV) are relatively frequent. They may raise concern about
      fetal wellbeing. Only occasionally they may lead to an emergency cesarean
      section. METHODS: Prospective cohort study in 980 women (> 34 weeks gestation)
      with a singleton fetus in breech presentation. During and after external cephalic
      version (ECV) FHR abnormalities were recorded. Obstetric variables and delivery
      outcome were evaluated. Primary outcome was to identify which fetuses are at risk
      for FHR abnormalities. Secondary outcome was to identify a possible relationship
      between FHR abnormalities during and after ECV and mode of delivery and fetal
      distress during subsequent labor. RESULTS: The overall success rate of ECV was
      60% and in 9% of the attempts there was an abnormal FHR pattern. In two cases FHR
      abnormalities after ECV led to an emergency CS. Estimated fetal weight per 100 g
      (OR 0.90, CI: 0.87-0.94) and longer duration of the ECV-procedure (OR 1.13, CI:
      1.05-1.21) were factors significantly associated with the occurrence of FHR
      abnormalities. FHR abnormalities were not associated with the mode of delivery or
      the occurrence of fetal distress during subsequent labor. CONCLUSIONS: FHR
      abnormalities during and after ECV are more frequent with lower estimated fetal
      weight and longer duration of the procedure. FHR abnormalities during and after
      ECV have no consequences for subsequent mode of delivery. They do not predict
      whether fetal distress will occur during labor. TRIAL REGISTRATION: The Eindhoven
      Breech Intervention Study, NCT00516555 . Date of registration: August 13, 2007.

PMID- 29041924
TI  - The value of repeat radial-probe endobronchial ultrasound-guided transbronchial
      biopsy after initial non-diagnostic results in patients with peripheral pulmonary
      lesions.
AB  - BACKGROUND: Radial-probe endobronchial ultrasound (rEBUS)-guided transbronchial
      biopsy (TBB) is invaluable in the diagnosis of peripheral pulmonary lesions
      (PPLs); however, in certain instances, the procedure has to be repeated because
      of initial non-diagnostic procedure(s). Little if any literature has been
      published on this issue. Therefore, the aim of this study was to investigate the
      utility of repeat rEBUS-guided TBB in achieving a definitive diagnosis of PPLs.
      METHODS: All patients who underwent rEBUS-guided TBB of PPLs at National Taiwan
      University Hospital between 2011 and 2015 and had a repeat procedure after non
      diagnostic initial procedures were identified as the study subjects. The primary
      outcome of interest was the diagnostic yield of repeat rEBUS-guided TBB for PPLs.
      Also, we sought to discover features associated with the yield of repeat
      procedures. RESULTS: Forty-three (11%) out of 384 patients with initial non
      diagnostic TBB were included for analysis. A diagnosis of PPLs was able to be
      confirmed with repeat TBB in 23(53%) patients. The pathology of the first TBB was
      significantly associated with the yield of repeat procedures (P = 0.011).
      Further, patients with normal lung tissue in initial pathology rarely (2/12, 17%)
      had a definite diagnosis on repeat TBB. Yet, patients with pathology showing
      atypical cells and other non-specific findings were more likely (21/31, 68%) to
      obtain a confirmed diagnosis. The diagnostic yield of repeat procedures was not
      affected by the size, location or CT appearance of the lesions, or position of
      the rEBUS probe. No death or other serious adverse events occurred with the
      repeat rEBUS-guided procedures. CONCLUSIONS: If clinically indicated, it is
      reasonable to repeat rEBUS-guided TBB after an initial non-diagnostic procedure
      as the diagnostic yield will be at least 50% and the side effect profile is
      favorable.

PMID- 29041925
TI  - Correction to: Socioeconomic inequalities in smoking habits are still increasing
      in Italy.

PMID- 29041926
TI  - Prevalence and factors associated with intestinal parasites among food handlers
      of food and drinking establishments in Aksum Town, Northern Ethiopia.
AB  - BACKGROUND: Various epidemiological studies indicate that the prevalence of
      intestinal parasites is high in developing countries and those parasites are
      major public health importance in Sub-Saharan Africa. Their distribution is
      mainly associated with poor personal hygiene, environmental sanitation and lack
      of access to clean water. This study was conducted to estimate the prevalence of
      intestinal parasitic infection and identify factors associated with intestinal
      parasitic infection among food handlers in the Aksum Town of Tigray Regional
      State, North Ethiopia. METHODS: A cross-sectional study design was used among 400
      randomly selected food handlers who were selected as respondents. Data were
      collected by face to face interviewer administered questionnaire supplemented
      with observational checklist. Fresh stool samples were collected from respondents
      and were examined microscopically for the presence of any of intestinal parasites
      using standard laboratory methods. Multivariable logistic regression model using
      Adjusted Odds Ratio (AOR) and 95% Confidence Interval (CI) was fitted to analyze
      the independent predictors of intestinal parasitic infections. RESULT: The mean
      age of the food handlers included in this study was 26.0 years. Of the total
      respondents, 72.5% were females, 63% have completed at least secondary school
      educational level. Five species of Intestinal Parasites (IPs) were identified.
      The overall prevalence of being infected with at least one intestinal parasite
      was 14.5%, 95% CI (11.3, 18.0). The odds of being positive for at least one
      intestinal parasitic infection was 12.3 times higher among food handlers who
      practice medical checkup every 9 months compared to those who have a medical
      checkup every 3 months. The odds of being positive for intestinal parasitic
      infection was 3 times higher among food handlers with no formal education
      compared to those who have a level of education secondary school and above. Food
      handlers who received food hygiene and safety training were 66% less likely to be
      positive for at least one intestinal parasitic infection as compared to those who
      did not receive training. CONCLUSION: Prevalence of parasitic infection among
      food handlers observed in the current study is relatively low but is still a
      public health importance. Number of medical checkup, training in food hygiene and
      safety, feedback from customers and level of education were significantly
      associated with reduced odds of being infected with parasitic infection. Hence,
      these factors should be focused by policy makers and implementers to further
      bring the prevalence below the level of public health importance.

PMID- 29041927
TI  - Diagnostic performance of the loop-mediated isothermal amplification (LAMP) based
      illumigene(r) malaria assay in a non-endemic region.
AB  - BACKGROUND: Light microscopy and antigen-based rapid diagnostic tests are the
      primary diagnostic tools for detecting malaria, although being labour-intensive
      and frequently challenged by lack of personnel's experience and low levels of
      parasite density. The latter being especially important in non-endemic settings.
      Novel molecular techniques aim to overcome this drawback. The objective of this
      study was to assess the diagnostic performance of the illumigene malaria assay(r)
      (Meridian Bioscience) compared to microscopy, RDT and real-time PCR. This loop
      mediated isothermal amplification (LAMP) assay is a qualitative in vitro
      diagnostic test for the direct detection of Plasmodium spp. DNA in human venous
      whole blood samples. METHODS: The illumigene assay was assessed on a
      retrospective panel of stored blood samples (n = 103) from returned travellers
      and external quality control samples (n = 12). Additionally the assay was
      prospectively assessed on 30 fresh routine samples with a request for malaria
      diagnosis. The illumigene assay was compared to microscopy, RDT and Plasmodium
      species specific real-time PCR. RESULTS: In the retrospective evaluation, the
      illumigene assay showed 100% agreement with the real-time PCR, RDT and microscopy
      yielding a sensitivity and specificity of 100% (95% CI 95.1-100% and 89.7-100%,
      respectively). Seven samples from patients recently treated for Plasmodium
      falciparum infection that were RDT positive and microscopy negative yielded
      positive test results. The performance of the illumigene assay equals that of
      microscopy combined with RDT in the prospective panel with three false negative
      RDT results and one false negative microscopy result. Excellent concordance with
      PCR was observed. The limit of detection of the assay approached 0.5 parasites/uL
      for both P. falciparum and Plasmodium vivax. CONCLUSION: In non-endemic regions
      where the diagnostic process for malaria infections is questioned by lack of
      experience and low levels of parasite densities, the illumigene assay can be of
      value. Due to its high sensitivity, the LAMP assay may be considered as primary
      diagnostic test. The results of this study indicate that negative screen results
      do not need further confirmation. However, before implementation, this approach
      needs to be confirmed in larger, prospective studies. A shortcoming of this assay
      is that no species identification nor determination of parasite density are
      possible.

PMID- 29041928
TI  - The TLR3/TICAM-1 signal constitutively controls spontaneous polyposis through
      suppression of c-Myc in Apc Min/+ mice.
AB  - BACKGROUND: Intestinal tumorigenesis is promoted by myeloid differentiation
      primary response gene 88 (MyD88) activation in response to the components of
      microbiota in Apc Min/+ mice. Microbiota also contains double-stranded RNA
      (dsRNA), a ligand for TLR3, which activates the toll-like receptor adaptor
      molecule 1 (TICAM-1, also known as TRIF) pathway. METHODS: We established Apc
      Min/+ Ticam1 -/- mice and their survival was compared to survival of Apc Min/+
      Myd88 -/- and wild-type (WT) mice. The properties of polyps were investigated
      using immunofluorescence staining and RT-PCR analysis. RESULTS: We demonstrate
      that TICAM-1 is essential for suppression of polyp formation in Apc Min/+ mice.
      TICAM-1 knockout resulted in shorter survival of mice compared to WT mice or mice
      with knockout of MyD88 in the Apc Min/+ background. Polyps were more frequently
      formed in the distal intestine of Apc Min/+ Ticam1 -/- mice than in Apc Min/+
      mice. Infiltration of immune cells such as CD11b+ and CD8alpha+ cells into the
      polyps was detected histologically. CD11b and CD8alpha mRNAs were increased in
      polyps of Apc Min/+ Ticam1 -/- mice compared to Apc Min/+ mice. Gene expression
      of inducible nitric oxide synthase (iNOS), interferon (IFN)-gamma, CXCL9 and IL
      12p40 was increased in polyps of Apc Min/+ Ticam1 -/- mice. mRNA and protein
      expression of c-Myc, a critical transcription factor for inflammation-associated
      polyposis, were increased in polyps of Apc Min/+ Ticam1 -/- mice. A Lactobacillus
      strain producing dsRNA was detected in feces of Apc Min/+ mice. CONCLUSION: These
      results imply that the TLR3/TICAM-1 pathway inhibits polyposis through
      suppression of c-Myc expression and supports long survival in Apc Min/+ mice.

PMID- 29041929
TI  - Absence of Plasmodium inui and Plasmodium cynomolgi, but detection of Plasmodium
      knowlesi and Plasmodium vivax infections in asymptomatic humans in the Betong
      division of Sarawak, Malaysian Borneo.
AB  - BACKGROUND: Plasmodium knowlesi, a simian malaria parasite, has become the main
      cause of malaria in Sarawak, Malaysian Borneo. Epidemiological data on malaria
      for Sarawak has been derived solely from hospitalized patients, and more accurate
      epidemiological data on malaria is necessary. Therefore, a longitudinal study of
      communities affected by knowlesi malaria was undertaken. METHODS: A total of 3002
      blood samples on filter paper were collected from 555 inhabitants of 8 longhouses
      with recently reported knowlesi malaria cases in the Betong Division of Sarawak,
      Malaysian Borneo. Each longhouse was visited bimonthly for a total of 10 times
      during a 21-month study period (Jan 2014-Oct 2015). DNA extracted from blood
      spots were examined by a nested PCR assay for Plasmodium and positive samples
      were then examined by nested PCR assays for Plasmodium falciparum, Plasmodium
      vivax, Plasmodium malariae, Plasmodium ovale, Plasmodium knowlesi, Plasmodium
      cynomolgi and Plasmodium inui. Blood films of samples positive by PCR were also
      examined by microscopy. RESULTS: Genus-specific PCR assay detected Plasmodium DNA
      in 9 out of 3002 samples. Species-specific PCR identified 7 P. knowlesi and one
      P. vivax. Malaria parasites were observed in 5 thick blood films of the PCR
      positive samples. No parasites were observed in blood films from one knowlesi-,
      one vivax- and the genus-positive samples. Only one of 7 P. knowlesi-infected
      individual was febrile and had sought medical treatment at Betong Hospital the
      day after sampling. The 6 knowlesi-, one vivax- and one Plasmodium-infected
      individuals were afebrile and did not seek any medical treatment. CONCLUSIONS:
      Asymptomatic human P. knowlesi and P. vivax malaria infections, but not P.
      cynomolgi and P. inui infections, are occurring within communities affected with
      malaria.

PMID- 29041930
TI  - Renal cell -like carcinoma of the nasal cavity: a case report and review of the
      literature.
AB  - BACKGROUND: Sinonasal renal cell-like carcinoma (SRCLC) is an extremely rare low
      malignant tumor arising in the sinonasal tract, with histological mimicry of
      renal cell carcinoma. CASE PRESENTATION: We present a case of sinonasal renal
      cell-like carcinoma in a 63-year-old male patient. Computer tomography(CT)
      scanning revealed a soft tissue mass at the left nasal cavity and choana.
      Histologically, the predominant tumor architecture was follicular to glandular
      with intervening fibrous septa. The tumor cells were uniform cuboidal to
      polyhedral with abundant clear or eosinophilic cytoplasm. Immunohistochemically,
      the tumor cells were strongly positive for CK7, EMA, vimentin, SOX10, S-100, and
      focally positive for CA9. During 6 months of follow-up, there was no clinical or
      radiological evidence of recurrence or metastasis. CONCLUSION: SRCLC has
      microscopic features which overlap with tumors that contain clear cells. Thus,
      several other tumors must be considered in the differential diagnosis of a tumor
      of the sinonasal region with clear cells, especially metastatic renal clear cell
      carcinoma. SRCLC is an indolent tumor and none of the reported SRCLC patients had
      metastatic disease.

PMID- 29041931
TI  - Reprogramming of stromal fibroblasts by SNAI2 contributes to tumor desmoplasia
      and ovarian cancer progression.
AB  - BACKGROUND: Molecular profiling in ovarian cancer (OC) revealed that the
      desmoplasia subtype presented the poorest prognosis, highlighting the
      contribution of stromal fibroblasts in tumor progression. This study aimed to
      investigate the molecular characteristics of SNAI2 driving the transcriptional
      reprogramming of fibroblasts within tumors. METHODS: SNAI2 expression was
      evaluated in microdissected profiles of various cancers and in various molecular
      subtypes of OC. Gene set enrichment analysis (GSEA) and single sample GSEA
      (ssGSEA) were performed to explore the correlation between SNAI2 and stromal
      fibroblast activation. The SNAI2 defined signature in the mesenchymal OC subtype
      was identified through an integrative analysis of the TCGA and the Tothill
      datasets. The predictive value of this signature was validated in independent
      datasets. SNAI2 expression alteration influence of tumor growth in primary CAFs
      was evaluated in 3D organotypic and murine xenograft models. RESULTS: We
      demonstrated that SNAI2 was frequently activated in the tumor stroma, correlated
      with fibroblast activation and worse patient outcome in OC. SNAI2 transformed
      normal fibroblasts to a CAF-like state and boosted their tumor-supporting role in
      3D organotypic culture and in OC xenograft model. SNAI2 drove a transcriptional
      signature in the mesenchymal subtype of OC that contributed to tumor desmoplasia,
      which fed back to increase SNAI2 expression and sustain fibroblast activation.
      CONCLUSIONS: Our results address the role of SNAI2 in reprogramming stromal
      fibroblasts. The identified SNAI2 mesenchymal signature has both a predictive
      value and biological relevance and might be a therapeutic target for stroma
      oriented therapy against the desmoplasia OC subtype.

PMID- 29041932
TI  - STAMPS: development and verification of swallowing kinematic analysis software.
AB  - BACKGROUND: Swallowing impairment is a common complication in various geriatric
      and neurodegenerative diseases. Swallowing kinematic analysis is essential to
      quantitatively evaluate the swallowing motion of the oropharyngeal structures.
      This study aims to develop a novel swallowing kinematic analysis software, called
      spatio-temporal analyzer for motion and physiologic study (STAMPS), and verify
      its validity and reliability. METHODS: STAMPS was developed in MATLAB, which is
      one of the most popular platforms for biomedical analysis. This software was
      constructed to acquire, process, and analyze the data of swallowing motion. The
      target of swallowing structures includes bony structures (hyoid bone, mandible,
      maxilla, and cervical vertebral bodies), cartilages (epiglottis and arytenoid),
      soft tissues (larynx and upper esophageal sphincter), and food bolus. Numerous
      functions are available for the spatiotemporal parameters of the swallowing
      structures. Testing for validity and reliability was performed in 10 dysphagia
      patients with diverse etiologies and using the instrumental swallowing model
      which was designed to mimic the motion of the hyoid bone and the epiglottis.
      RESULTS: The intra- and inter-rater reliability tests showed excellent agreement
      for displacement and moderate to excellent agreement for velocity. The Pearson
      correlation coefficients between the measured and instrumental reference values
      were nearly 1.00 (P < 0.001) for displacement and velocity. The Bland-Altman
      plots showed good agreement between the measurements and the reference values.
      CONCLUSIONS: STAMPS provides precise and reliable kinematic measurements and
      multiple practical functionalities for spatiotemporal analysis. The software is
      expected to be useful for researchers who are interested in the swallowing motion
      analysis.

PMID- 29041933
TI  - Silence sexual and reproductive health discussions and we fuel the rise of
      HIV/AIDS in sub-Saharan Africa.
AB  - In the mid 1990s, the HIV epidemic was initially impacting South Africa. Fear,
      stigma and denial surrounding sexual practices undermined treatment access and
      prevention initiatives. Significant strides have been made in reducing the HIV
      epidemic in South Africa and other areas in sub-Saharan Africa through effective
      programming and funding of prevention programs. Reinstatement of the Mexico City
      Policy threatens to negatively impact gains made in the HIV/AIDS community.
      Recognition that communication is essential to effective reproductive health and
      HIV/AIDS programming needs to be recognized by politicians enacting the Mexico
      City Policy and the possibility of viewing a rise in HIV/AIDS incidence in sub
      Saharan Africa.

PMID- 29041934
TI  - H syndrome: 5 new cases from the United States with novel features and responses
      to therapy.
AB  - BACKGROUND: H Syndrome is an autosomal recessive disorder characterized by
      cutaneous hyperpigmentation, hypertrichosis, and induration with numerous
      systemic manifestations. The syndrome is caused by mutations in SLC29A3, a gene
      located on chromosome 10q23, which encodes the human equilibrative transporter 3
      (hENT3). Less than 100 patients with H syndrome have been described in the
      literature, with the majority being of Arab descent, and only a few from North
      America. CASE PRESENTATION: Here we report five pediatric patients from three
      medical centers in the United States who were identified to have H syndrome by
      whole exome sequencing. These five patients, all of whom presented to pediatric
      rheumatologists prior to diagnosis, include two of Northern European descent,
      bringing the total number of Caucasian patients described to three. The patients
      share many of the characteristics previously reported with H syndrome, including
      hyperpigmentation, hypertrichosis, short stature, insulin-dependent diabetes,
      arthritis and systemic inflammation, as well as some novel features, including
      selective IgG subclass deficiency and autoimmune hepatitis. They share genetic
      mutations previously described in patients of the same ethnic background, as well
      as a novel mutation. In two patients, treatment with prednisone improved
      inflammation, however both patients flared once prednisone was tapered. In one of
      these patients, treatment with tocilizumab alone resulted in marked improvement
      in systemic inflammation and growth. The other had partial response to
      prednisone, azathioprine, and TNF inhibition; thus, his anti-TNF biologic was
      recently switched to tocilizumab due to persistent polyarthritis. Another patient
      improved on Methotrexate, with further improvement after the addition of
      tocilizumab. CONCLUSION: H syndrome is a rare autoinflammatory syndrome with
      pleiotropic manifestations that affect multiple organ systems and is often
      mistaken for other conditions. Rheumatologists should be aware of this syndrome
      and its association with arthritis. It should be considered in patients with
      short stature and systemic inflammation, particularly with cutaneous findings.
      Some patients respond to treatment with biologics alone or in combination with
      other immune suppressants; in particular, treatment of systemic inflammation with
      IL-6 blockade appears to be promising. Overall, better identification and
      understanding of the pathophysiology may help devise earlier diagnosis and better
      treatment strategies.

PMID- 29041935
TI  - A long non-coding RNA HOTTIP expression is associated with disease progression
      and predicts outcome in small cell lung cancer patients.
AB  - BACKGROUND: Despite progress in treatment of small cell lung cancer (SCLC), the
      biology of the tumor still remains poorly understood. Recently, we globally
      investigated the contributions of lncRNA in SCLC with a special focus on sponge
      regulatory network. Here we report lncRNA HOTTIP, which is specifically amplified
      in SCLC, is associated with SCLC proliferation and poor prognosis of patients.
      METHODS: RT-qPCR was used to investigate the expression of HOTTIP in SCLC tissues
      and cell lines. The role of HOTTIP in SCLC cell proliferation was demonstrated by
      CCK8 assay, colony formation assay, flow cytometry analysis and in vivo SCLC
      xenograft model in nude mice through HOTTIP loss- and gain-of-function effects.
      Western blot assay was used to evaluate gene expression in cell lines at protein
      level. RNA pull-down, Mass spectrometry and RNA binding protein
      immunoprecipitation (RIP) were performed to confirm the molecular mechanism of
      HOTTIP involved in SCLC progression. RESULTS: We found that HOTTIP was
      overexpressed in SCLC tissues, and its expression was correlated with the
      clinical stage and the shorter survival time of SCLC patients. Moreover, HOTTIP
      knockdown could impair cell proliferation, affect the cell cycle and inhibit
      tumor growth of mice, while HOTTIP overexpression might enhance cell
      proliferation and cell cycle in vitro and in vivo. Mechanistic investigations
      showed that HOTTIP functions as an oncogene in SCLC progression by sponging miR
      574-5p and affecting the expression of polycomb group protein EZH1. CONCLUSIONS:
      Overall, we identified that HOTTIP was involved in SCLC tumorigenesis through the
      ceRNA network "HOTTIP/miR-574-5p/EZH1". Our findings not only illuminate how
      HOTTIP confers an oncogenic function in SCLC pathogenesis, but also underscore a
      novel gene expression governing hallmarks in the disease.

PMID- 29041936
TI  - Pathways to increased coverage: an analysis of time trends in contraceptive need
      and use among adolescents and young women in Kenya, Rwanda, Tanzania, and Uganda.
AB  - BACKGROUND: Despite efforts to make contraceptive services more "youth friendly,"
      unmet need for contraception among young women in sub-Saharan Africa remains
      high. For health systems to effectively respond to the reproductive health needs
      of a growing youth population, it is imperative to understand their contraceptive
      needs and service seeking practices. This paper describes changes over time in
      contraceptive need, use, and sources of care among young women in four East
      African countries. METHODS: We used three rounds of DHS data from Kenya, Rwanda,
      Tanzania, and Uganda to examine time trends from 1999 to 2015 in met need for
      modern contraception, method mix, and source of care by sector (public or
      private) and type of provider among young women aged 15-24 years. We assessed
      disparities in contraceptive coverage improvements over time between younger (15
      24 years) and older women (25-49 years) using a difference-in-differences
      approach. RESULTS: Met need for contraception among women aged 15-24 years
      increased over time, ranging from a 20% increase in Tanzania to more than a 5
      fold increase in Rwanda. Improvements in met need were greater among older women
      compared to younger women in Rwanda and Uganda, and higher among younger women in
      Kenya. Injectables have become the most popular contraceptive choice among young
      women, with more than 50% of modern contraceptive users aged 15-24 years
      currently using the method in all countries except for Tanzania, where condoms
      and injectables are used by 38% and 35% of young users, respectively. More than
      half of young women in Tanzania and Uganda receive contraceptives from the
      private sector; however, while the private sector played an important role in
      meeting the growing contraceptive needs among young women in Tanzania, increased
      use of public sector services drove expanded access in Kenya, Rwanda, and Uganda.
      CONCLUSIONS: Our study shows that contraceptive use increased among young East
      African women, yet, unmet need remains high. As youth populations continue to
      grow, governments must develop more targeted strategies for expanding access to
      reproductive health services for young women. Engaging the private sector and
      task-shifting to lower-level providers offer promising approaches; however,
      additional research is needed to identify the key facilitators and barriers to
      the success of these strategies in different contexts.

PMID- 29041937
TI  - Biocompatible coated magnetosome minerals with various organization and cellular
      interaction properties induce cytotoxicity towards RG-2 and GL-261 glioma cells
      in the presence of an alternating magnetic field.
AB  - BACKGROUND: Biologics magnetics nanoparticles, magnetosomes, attract attention
      because of their magnetic characteristics and potential applications. The aim of
      the present study was to develop and characterize novel magnetosomes, which were
      extracted from magnetotactic bacteria, purified to produce apyrogen magnetosome
      minerals, and then coated with Chitosan, Neridronate, or Polyethyleneimine. It
      yielded stable magnetosomes designated as M-Chi, M-Neri, and M-PEI, respectively.
      Nanoparticle biocompatibility was evaluated on mouse fibroblast cells (3T3),
      mouse glioblastoma cells (GL-261) and rat glioblastoma cells (RG-2). We also
      tested these nanoparticles for magnetic hyperthermia treatment of tumor in vitro
      on two tumor cell lines GL-261 and RG-2 under the application of an alternating
      magnetic field. Heating, efficacy and internalization properties were then
      evaluated. RESULTS: Nanoparticles coated with chitosan, polyethyleneimine and
      neridronate are apyrogen, biocompatible and stable in aqueous suspension. The
      presence of a thin coating in M-Chi and M-PEI favors an arrangement in chains of
      the magnetosomes, similar to that observed in magnetosomes directly extracted
      from magnetotactic bacteria, while the thick matrix embedding M-Neri leads to
      structures with an average thickness of 3.5 um2 per magnetosome mineral. In the
      presence of GL-261 cells and upon the application of an alternating magnetic
      field, M-PEI and M-Chi lead to the highest specific absorption rates of 120-125
      W/gFe. Furthermore, while M-Chi lead to rather low rates of cellular
      internalization, M-PEI strongly associate to cells, a property modulated by the
      application of an alternating magnetic field. CONCLUSIONS: Coating of purified
      magnetosome minerals can therefore be chosen to control the interactions of
      nanoparticles with cells, organization of the minerals, as well as heating and
      cytotoxicity properties, which are important parameters to be considered in the
      design of a magnetic hyperthermia treatment of tumor.

PMID- 29041938
TI  - Development of breath test for pneumoconiosis: a case-control study.
AB  - BACKGROUND: Lipid peroxidation plays an important role in the pathogenesis of
      pneumoconiosis. Volatile organic compounds (VOCs) generated from lipid
      peroxidation might be used to detect pneumoconiosis. The objective of this study
      was to develop a breath test for pneumoconiosis. METHODS: A case-control study
      was designed. Breath and ambient air were analysed by gas chromatography/mass
      spectrometry. After blank correction to prevent contamination from ambient air,
      we used canonical discriminant analysis (CDA) to assess the discrimination
      accuracy and principal component analysis (PCA) to generate a prediction score.
      The prediction accuracy was calculated and validated using the International
      Classification of Radiographs of the Pneumoconiosis criteria combined with an
      abnormal pulmonary function test as a reference standard. We generated a receiver
      operator characteristic (ROC) curve and calculated the area under the ROC curve
      (AUC) to estimate the screening accuracy of the breath test. RESULTS: We enrolled
      200 stone workers. After excluding 5 subjects with asthma and 16 subjects who
      took steroids or nonsteroidal anti-inflammatory drugs, a total of 179 subjects
      were used in the final analyses, which included 25 cases and 154 controls. By
      CDA, 88.8% of subjects were correctly discriminated by their exposure status and
      the presence of pneumoconiosis. After excluding the VOCs of automobile exhaust
      and cigarette smoking, pentane and C5-C7 methylated alkanes constituted the major
      VOCs in the breath of persons with pneumoconiosis. Using the prediction score
      generated from PCA, the ROC-AUC was 0.88 (95% CI = 0.80-0.95), and the mean ROC
      AUC of 5-fold cross-validation was 0.90. The breath test had good accuracy for
      pneumoconiosis diagnosis. CONCLUSION: The analysis of breath VOCs has potential
      in the screening of pneumoconiosis for its non-invasiveness and high accuracy. We
      suggest that a multi-centre study is warranted and that all procedures must be
      standardized before clinical application.

PMID- 29041939
TI  - Evidence-based decision-making for diagnostic and therapeutic methods: the
      changing landscape of assessment approaches in Germany.
AB  - This article examines the current status and most important changes over time to
      the legislative framework on the health technology assessment-informed decision
      making process on diagnostic and therapeutic 'methods' in Germany. The relevant
      information was obtained through documentary analysis covering the period 1990 to
      2017. The findings show that, even if the outpatient care sector appears to be
      much more regulated than the inpatient sector (based on a strict separation of
      the two care settings), developments in Germany have led to a more tightened
      assessment framework, making the use of evidence a firm component in the decision
      making process. Nevertheless, a comprehensive approach for a systematic
      assessment of diagnostic and therapeutic 'methods' still does not exist.
      Readjustments of current regulations in Germany, such as the existing
      'Verbotsvorbehalt' (i.e. provision of a diagnostic and therapeutic 'method'
      possible unless actively delisted) in the inpatient care setting, as well as
      further developments at the European level are needed in order to create a system
      that ensures early access to innovation under controlled study conditions.

PMID- 29041940
TI  - State of inequality in malaria intervention coverage in sub-Saharan African
      countries.
AB  - BACKGROUND: Scale-up of malaria interventions over the last decade have yielded a
      significant reduction in malaria transmission and disease burden in sub-Saharan
      Africa. We estimated economic gradients in the distribution of these efforts and
      of their impacts within and across endemic countries. METHODS: Using Demographic
      and Health Surveys we computed equity metrics to characterize the distribution of
      malaria interventions in 30 endemic countries proxying economic position with an
      asset-wealth index. Gradients were summarized in a concentration index, tabulated
      against level of coverage, and compared among interventions, across countries,
      and against respective trends over the period 2005-2015. RESULTS: There remain
      broad differences in coverage of malaria interventions and their distribution by
      wealth within and across countries. In most, economic gradients are lacking or
      favor the poorest for vector control; malaria services delivered through the
      formal healthcare sector are much less equitable. Scale-up of interventions in
      many countries improved access across the wealth continuum; in some, these
      efforts consistently prioritized the poorest. Expansions in control programs
      generally narrowed coverage gaps between economic strata; gradients persist in
      countries where growth was slower in the poorest quintile or where baseline
      inequality was large. Despite progress, malaria is consistently concentrated in
      the poorest, with the degree of inequality in burden far surpassing that expected
      given gradients in the distribution of interventions. CONCLUSIONS: Economic
      gradients in the distribution of interventions persist over time, limiting
      progress toward equity in malaria control. We found that, in countries with large
      baseline inequality in the distribution of interventions, even a small bias in
      expansion favoring the least poor yielded large gradients in intervention
      coverage while pro-poor growth failed to close the gap between the poorest and
      least poor. We demonstrated that dimensions of disadvantage compound for the
      poor; a lack of economic gradients in the distribution of malaria services does
      not translate to equity in coverage nor can it be interpreted to imply equity in
      distribution of risk or disease burden. Our analysis testifies to the progress
      made by countries in narrowing economic gradients in malaria interventions and
      highlights the scope for continued monitoring of programs with respect to equity.

PMID- 29041941
TI  - Disentangling the effects of a multiple behaviour change intervention for
      diarrhoea control in Zambia: a theory-based process evaluation.
AB  - BACKGROUND: Diarrhoea is a leading cause of child death in Zambia. As elsewhere,
      the disease burden could be greatly reduced through caregiver uptake of existing
      prevention and treatment strategies. We recently reported the results of the
      Komboni Housewives intervention which tested a novel strategy employing motives
      including affiliation and disgust to improve caregiver practice of four diarrhoea
      control behaviours: exclusive breastfeeding; handwashing with soap; and correct
      preparation and use of oral rehydration salts (ORS) and zinc. The intervention
      was delivered via community events (women's forums and road shows), at health
      clinics (group session) and via radio. A cluster randomised trial revealed that
      the intervention resulted in a small improvement in exclusive breastfeeding
      practices, but was only associated with small changes in the other behaviours in
      areas with greater intervention exposure. This paper reports the findings of the
      process evaluation that was conducted alongside the trial to investigate how
      factors associated with intervention delivery and receipt influenced caregiver
      uptake of the target behaviours. METHODS: Process data were collected from the
      eight peri-urban and rural intervention areas throughout the six-month
      implementation period and in all 16 clusters 4-6 weeks afterwards. Intervention
      implementation (fidelity, reach, dose delivered and recruitment strategies) and
      receipt (participant engagement and responses, and mediators) were explored
      through review of intervention activity logs, unannounced observation of
      intervention events, semi-structured interviews, focus groups with implementers
      and intervention recipients, and household surveys. Evaluation methods and
      analyses were guided by the intervention's theory of change and the evaluation
      framework of Linnan and Steckler. RESULTS: Intervention reach was lower than
      intended: 39% of the surveyed population reported attending one or more face-to
      face intervention event, of whom only 11% attended two or more intervention
      events. The intervention was not equally feasible to deliver in all settings:
      fewer events took place in remote rural areas, and the intervention did not
      adequately penetrate communities in several peri-urban sites where the population
      density was high, the population was slightly higher socio-economic status,
      recruitment was challenging, and numerous alternative sources of entertainment
      existed. Adaptations made by the implementers affected the fidelity of
      implementation of messages for all target behaviours. Incorrect messages were
      consequently recalled by intervention recipients. Participants were most
      receptive to the novel disgust and skills-based interactive demonstrations
      targeting exclusive breastfeeding and ORS preparation respectively. However,
      initial disgust elicitation was not followed by a change in associated
      psychological mediators, and social norms were not measurably changed.
      CONCLUSIONS: The lack of measured behaviour change was likely due to issues with
      both the intervention's content and its delivery. Achieving high reach and
      intensity in community interventions delivered in diverse settings is
      challenging. Achieving high fidelity is also challenging when multiple behaviours
      are targeted for change. Further work using improved tools is needed to explore
      the use of subconscious motives in behaviour change interventions. To better
      uncover how and why interventions achieve their measured effects, process
      evaluations of complex interventions should develop and employ frameworks for
      investigation and interpretation that are structured around the intervention's
      theory of change and the local context. TRIAL REGISTRATION: The study was
      registered as part of the larger trial on 5 March 2014 with ClinicalTrials.gov:
      NCT02081521 .

PMID- 29041942
TI  - Patient-reported health-related quality of life, work productivity, and activity
      impairment during treatment with ALO-02 (extended-release oxycodone and
      sequestered naltrexone) for moderate-to-severe chronic low back pain.
AB  - BACKGROUND: The efficacy of ALO-02, an abuse-deterrent formulation containing
      extended-release oxycodone and sequestered naltrexone, in the treatment of
      chronic low back pain (CLBP) was studied in a 12-week randomized controlled
      trial. Primary efficacy endpoint results have been published previously (Rauck et
      al., 2015). The current paper focuses on patient-reported outcomes for health
      related quality of life (HRQL), work productivity, and activity impairment that
      were assessed during this study. METHODS: This was a double-blind, placebo
      controlled, randomized withdrawal study in patients with moderate-to-severe CLBP.
      After a screening period (<=2 weeks), patients entered an open-label titration
      period (4-6 weeks). Treatment responders were then randomized to a double-blind
      placebo-controlled treatment period (12 weeks). HRQL was assessed using changes
      in the Short Form-36 v2 Health Survey (SF-36v2) and the EuroQol-5 Dimensions
      Health Questionnaire 3-Level version (EQ-5D-3L). Work productivity and regular
      activities were evaluated using the Work Productivity and Activity Impairment
      Questionnaire: Specific Health Problem (WPAI:SHP). RESULTS: A total of 410
      patients received ALO-02 during the open-label titration period, of which 280
      (intent-to-treat (ITT) population) were treated during the double-blind placebo
      controlled treatment period (placebo, n = 134; ALO-02, n = 146). Significant
      improvement was observed for all SF-36v2 subscales and component scores (p <
      0.005) and the EQ-5D-3L summary index and visual analog scale (p < 0.0001) during
      the titration period. Improvement was also significant (p < 0.0001) for all
      WPAI:SHP outcomes except 'work time missed due to CLBP' for the titration period.
      Significant differences favoring ALO-02 compared with placebo were only observed
      for the SF-36v2 Bodily Pain subscale (p <= 0.0232; ITT population) during the
      double-blind treatment period and the overall study period (screening to the end
      of the double-blind treatment period). The percentage change in activity
      impairment due to low back pain subscale of the WPAI:SHP significantly favored
      ALO-02 compared with placebo for the ITT population when considering the overall
      study period (p = 0.0040). CONCLUSIONS: HRQL, work productivity, and activity
      impairment may be improved with ALO-02 treatment. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01571362 , registered April 3, 2012.

PMID- 29041943
TI  - Human umbilical cord Wharton jelly cells promote extra-pancreatic insulin
      formation and repair of renal damage in STZ-induced diabetic mice.
AB  - BACKGROUND: We evaluated the therapeutic effect and fate of high doses of human
      umbilical cord Wharton jelly cells (hUCWJCs) after IP administration to
      streptozotocin (STZ)-induced diabetic mice. METHODS: Type 1 diabetes (T1D) was
      induced in Kunming mice via IP injection of STZ. hUCWJCs were labeled with 1,1'
      dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). Diabetic
      animals with sustained hyperglycemia for at least 2 weeks were administered 1 *
      107 Dil-hUCWJCs via intraperitoneal injection. Insulin, glucagon and PDX-1 were
      detected by immunofluorescence with confocal microscopy. Serum mouse and human C
      peptide was assayed in blood collected via intracardiac puncture. Specific beta
      cell differentiation markers and human DNA were assessed using qPCR performed
      with 200 ng of target DNA. RESULTS: hUCWJCs migrated to the STZ-damaged organs
      and contributed to lower blood glucose levels in 30% of the treated mice.
      Confocal microscopy revealed the presence of resident insulin-positive cells in
      the liver and kidneys. hUCWJC-treated mice with restored hyperglycemia also
      showed increased serum mouse C-peptide levels. The qPCR results, particularly in
      the liver, revealed that after transplantation hUCWJCs upregulated genes of
      endocrine precursors but failed to express endocrine stage markers. Mice with
      restored hyperglycemia had reduced urinary volume and lacked glomerular
      hypertrophy, exhibiting a morphology resembling that of normal glomeruli.
      Moreover, we also verified that one of the possible mechanisms by which hUCWJCs
      exert immunosuppressive effects is through down-regulation of the cell surface
      receptor HLA-1. CONCLUSIONS: We confirmed the potential of IP administration of
      hUCWJCs and the capability of these cells to migrate to damaged tissues and
      promote insulin secretion from non-pancreatic local cells and to improve renal
      damage. These findings confer unique therapeutic properties to hUCWJCs,
      suggesting a promising future in the treatment of diabetes mellitus.

PMID- 29041944
TI  - Differential expression of porcine microRNAs in African swine fever virus
      infected pigs: a proof-of-concept study.
AB  - BACKGROUND: African swine fever (ASF) is a re-expanding devastating viral disease
      currently threatening the pig industry worldwide. MicroRNAs are a class of 17-25
      nucleotide non- coding RNAs that have been shown to have critical functions in a
      wide variety of biological processes, such as cell differentiation, cell cycle
      regulation, carcinogenesis, apoptosis, regulation of immunity as well as in viral
      infections by cleavage or translational repression of mRNAs. Nevertheless, there
      is no information about miRNA expression in an ASFV infection. METHODS: In this
      proof-of-concept study, we have analyzed miRNAs expressed in spleen and
      submandibular lymph node of experimentally infected pigs with a virulent (E75) or
      its derived attenuated (E75CV1) ASFV strain, as well as, at different times post
      infection with the virulent strain, by high throughput sequencing of small RNA
      libraries. RESULTS: Spleen presented a more differential expression pattern than
      lymph nodes in an ASFV infection. Of the most abundant miRNAs, 12 were
      differentially expressed in both tissues at two different times in infected
      animals with the virulent strain. Of these, miR-451, miR-145-5p, miR-181a and miR
      122 presented up-regulation at late times post-infection while miR-92a, miR-23a,
      miR-92b-3p, miR-126-5p, miR-126-3p, miR-30d, miR-23b and miR-92c showed down
      regulation. Of the 8 differentially expressed miRNAs identified at the same time
      post-infection in infected animals with the virulent strain compared with animals
      infected with its attenuated strain, miR-126-5p, miR-92c, miR-92a, miR-30e-5p and
      miR-500a-5p presented up-regulation whereas miR-125b, miR-451 and miR-125a were
      down-regulated. All these miRNAs have been shown to be associated with cellular
      genes involved in pathways related to the immune response, virus-host
      interactions as well as with several viral genes. CONCLUSION: The study of miRNA
      expression will contribute to a better understanding of African swine fever virus
      pathogenesis, essential in the development of any disease control strategy.

PMID- 29041945
TI  - Double calcaneal osteotomy for severe adolescent flexible flatfoot
      reconstruction.
AB  - BACKGROUND: The timing and strategy of treatment for flatfoot still remain
      controversial. It is a difficult problem when facing severe adolescent flexible
      flatfoot because a single procedure cannot realign flatfoot deformity
      effectively. METHODS: We reviewed 13 adolescent flexible flatfoot patients who
      underwent double calcaneal osteotomy during May 2012 to June 2015. The mean age
      of patients was 15.2 +/- 1.8 (range, 10-18) years. The American Orthopaedic Foot
      and Ankle Society Ankle-Hindfoot (AOFAS-AH) scores and SF-36 score were adopted
      to evaluate the preoperative and postoperative functions of the foot. Changes of
      hindfoot valgus angles, talonavicular uncoverage angles on AP view and talo-first
      metatarsal angles, and talar pitch angles and calcaneal pitch angles on the
      lateral film before and after surgery were measured. RESULTS: All 13 patients (15
      ft) were followed. The mean duration of follow-up was 34.5 +/- 15.7 (range, 21
      60) months. The hindfoot valgus angle improved from 16.5 +/- 4.1 to 2.9 +/- 1.6.
      On the foot AP view, the mean preoperative and postoperative talonavicular
      coverage angles were 24.9 +/- 8.5 and 6.5 +/- 3.6. On the lateral view of the
      foot, the average preoperative and postoperative talo-first metatarsal angles
      were 18.1 +/- 5.5 and 4.9 +/- 4.4. The mean preoperative and postoperative talar
      pitch angles were 36.4 +/- 4.7 and 24.0 +/- 5.6. The AOFAS-AH score improved from
      68.9 +/- 12.3 preoperatively to 94.6 +/- 3.9 postoperatively. CONCLUSION: With
      additional procedures, double calcaneal osteotomy was an effective method for
      severe adolescent flexible flatfoot.

PMID- 29041946
TI  - The role of B cell antigen receptors in mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is characterized by an aggressive clinical course and
      secondary resistance to currently available therapies in most cases. Therefore,
      despite recent advances in the treatment of this disease, it is still considered
      to be incurable in the majority of cases. MCL B cells retain their B cell antigen
      receptor (BCR) expression during and after neoplastic transformation. BCRs in MCL
      show distinct patterns of antigen selection and ongoing BCR signaling. However,
      little is known about the involved antigens and the mechanisms leading to
      lymphomagenesis and lymphoma progression in MCL. Recent preclinical and clinical
      studies have established a crucial role of the BCR and the potential of
      inhibiting its signaling in this disease. This has established the B cell antigen
      receptor signaling cascade as a very promising therapeutic target to improve
      outcome in MCL alone or in combination with chemo-immunotherapy in recent years.

PMID- 29041947
TI  - The Fear Reduction Exercised Early (FREE) approach to low back pain: study
      protocol for a randomised controlled trial.
AB  - BACKGROUND: Low back pain (LBP) is a major health issue associated with
      considerable health loss and societal costs. General practitioners (GPs) play an
      important role in the management of LBP; however, GP care has not been shown to
      be the most cost-effective approach unless exercise and behavioural counselling
      are added to usual care. The Fear Reduction Exercised Early (FREE) approach to
      LBP has been developed to assist GPs to manage LBP by empowering exploration and
      management of psychosocial barriers to recovery and provision of evidence-based
      care and information. The aim of the Low Back Pain in General Practice (LBPinGP)
      trial is to explore whether patients with LBP who receive care from GPs trained
      in the FREE approach have better outcomes than those who receive usual care.
      METHODS/DESIGN: This is a cluster randomised controlled superiority trial
      comparing the FREE approach with usual care for LBP management with investigator
      blinded assessment of outcomes. GPs will be recruited and then cluster randomised
      (in practice groups) to the intervention or control arm. Intervention arm GPs
      will receive training in the FREE approach, and control arm GPs will continue to
      practice as usual. Patients presenting to their GP with a primary complaint of
      LBP will be allocated on the basis of allocation of the GP they consult. We aim
      to recruit 60 GPs and 275 patients (assuming patients are recruited from 75% of
      GPs and an average of 5 patients per GP complete the study, accounting for 20%
      patient participant dropout). Patient participants and the trial statistician
      will be blind to group allocation throughout the study. Analyses will be
      undertaken on an intention-to-treat basis. The primary outcome will be back
      related functional impairment 6 months post-initial LBP consultation (interim
      data at 2 weeks, 6 weeks and 3 months), measured with the Roland-Morris
      Disability Questionnaire. Secondary patient outcomes include pain, satisfaction,
      quality of life, days off from work and costs of care. Secondary GP outcomes
      include beliefs about pain and impairment, GP confidence, and actual and reported
      clinical behaviour. Health economic and process evaluations will be conducted.
      DISCUSSION: In the LBPinGP trial, we will investigate providing an intervention
      during the first interaction a person with back pain has with their GP. Because
      the FREE approach is used within a normal GP consultation, if effective, it may
      be a cost-effective means of improving LBP care. TRIAL REGISTRATION: Australian
      New Zealand Clinical Trials Registry, ACTRN12616000888460 . Registered on 6 July
      2016.

PMID- 29041949
TI  - Incretins in patients with rheumatoid arthritis.
AB  - BACKGROUND: The precise mechanism linking systemic inflammation with insulin
      resistance (IR) in rheumatoid arthritis (RA) remains elusive. In the present
      study, we determined whether the incretin-insulin axis and incretin effect are
      disrupted in patients with RA and if they are related to the IR found in these
      patients. METHODS: We conducted a cross-sectional study that encompassed 361
      subjects without diabetes, 151 patients with RA, and 210 sex-matched control
      subjects. Insulin, C-peptide, glucagon-like peptide-1 (GLP-1), gastric inhibitory
      polypeptide (GIP), dipeptidyl peptidase 4 (DPP-4) soluble form, and IR indexes by
      homeostatic model assessment (HOMA2) were assessed. A multivariable analysis
      adjusted for IR-related factors was performed. Additionally, ten patients and ten
      control subjects underwent a 566-kcal meal test so that we could further study
      the postprandial differences of these molecules between patients and control
      subjects. RESULTS: Insulin, C-peptide, and HOMA2-IR indexes were higher in
      patients than in control subjects. This was also the case for GLP-1 (0.49 +/-
      1.28 vs. 0.71 +/- 0.22 ng/ml, p = 0.000) and GIP (0.37 +/- 0.40 vs. 1.78 +/- 0.51
      ng/ml, p = 0.000). These differences remained significant after multivariable
      adjustment including glucocorticoid intake. Disease Activity Score in 28 joints
      with erythrocyte sedimentation rate (beta coefficient 46, 95% CI 6-87, p = 0.026)
      and Clinical Disease Activity Index (beta coefficient 7.74, 95% CI 1.29-14.20, p
      = 0.019) were associated with DPP-4 serum levels. GLP-1 positively correlated
      with beta-cell function (HOMA2 of beta-cell production calculated with C-peptide)
      in patients but not in control subjects (interaction p = 0.003). The meal test in
      patients with RA revealed a higher total and late response AUC for glucose
      response, a later maximal response of C-peptide, and a flatter curve in GIP
      response. CONCLUSIONS: The incretin-insulin axis, both during fasting and
      postprandial, is impaired in patients with RA.

PMID- 29041948
TI  - Effect of levosimendan on prognosis in adult patients undergoing cardiac surgery:
      a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Small trials suggest that levosimendan is associated with a favorable
      outcome in patients undergoing cardiac surgery. However, recently published
      larger-scale trials did not provide evidence for a similar benefit from
      levosimendan. We performed a meta-analysis to assess the survival benefits of
      levosimendan in patients undergoing cardiac surgery and to investigate its
      effects in subgroups of patients with preoperative low-ejection fraction (EF).
      METHODS: We identified randomized clinical trials through 20 April 2017 that
      investigated levosimendan therapy versus control in patients undergoing cardiac
      surgery. Individual patient data from each study were compiled. Meta-analyses
      were performed for primary outcomes, secondary outcomes and serious adverse
      events, and subgroup analyses according to the preoperative EF of enrolled
      patients were also conducted. The risk of bias was assessed using the Cochrane
      risk-of-bias tool. RESULTS: Seventeen studies involving a total of 2756 patients
      were included. Levosimendan therapy was associated with a significant reduction
      in 30-day mortality (RR 0.67; 95% CI, 0.49 to 0.93; p = 0.02) and reduced the
      risk of death in single-center trials (RR 0.49; 95% CI, 0.30 to 0.79; p = 0.004)
      and in subgroup trials of inferior quality (RR 0.39; 95% CI, 0.17 to 0.92; p =
      0.02); however, in multicenter and in high-quality subgroup-analysis trials, no
      significant difference in mortality was observed between patients who received
      levosimendan therapy and controls (p > 0.05). However, in high-quality subgroup
      trials, levosimendan therapy was associated with reduced mortality in patients in
      a preoperative low-EF subgroup (RR 0.58; 95% CI, 0.38 to 0.88; p = 0.01).
      Similarly, only patients in the preoperative low-EF subgroup benefited in terms
      of reduced risk of renal replacement therapy (RR 0.54; 95% CI, 0.34 to 0.85; p =
      0.007). Furthermore, levosimendan therapy was associated with a significant
      reduction in intensive care unit (ICU) length of stay (MDR -17.19; 95% CI, -34.43
      to -2.94; p = 0.02). CONCLUSIONS: In patients undergoing cardiac surgery, the
      benefit of levosimendan in terms of survival was not shown in multicenter or in
      high-quality trials; however, levosimendan therapy was associated with reduced
      mortality in patients with preoperative ventricular systolic dysfunction.

PMID- 29041950
TI  - Convenience without disclosure: a formative research study of a proposed
      integrated methadone and antiretroviral therapy service delivery model in Dar es
      Salaam, Tanzania.
AB  - BACKGROUND: Though timely initiation of antiretroviral therapy (ART) is a vital
      component of effective HIV prevention, care and treatment, people who inject
      drugs are less likely to receive ART than their non-drug using counterparts. In
      an effort to increase access to ART for people who inject drugs, we examined
      perceived benefits, challenges, and recommendations for implementing an
      integrated methadone and ART service delivery model at an opioid treatment
      program (OTP) clinic in Dar es Salaam, Tanzania. METHODS: We conducted in-depth
      interviews with 12 providers and 20 HIV-positive patients at the Muhimbili
      National Hospital OTP clinic in early 2015. We used thematic content analysis to
      examine patient and provider perspectives of an integrated model. RESULTS:
      Respondents perceived that offering on-site CD4 testing and HIV clinical
      management at the OTP clinic would improve the timeliness and efficiency of the
      ART eligibility process, make HIV clinical care more convenient, mitigate stigma
      and discrimination in HIV care and treatment settings, and improve patient
      monitoring and ART adherence. However, perceived challenges included overburdened
      OTP clinic staff and limited space at the clinic to accommodate additional
      services. Limited privacy at the OTP clinic and its contribution to fear among
      HIV-positive patients of being stigmatized by their peers at the clinic was a
      common theme expressed particularly by patients, and often corroborated by
      providers. Co-dispensing ART and methadone at the clinic's pharmacy window was
      viewed as a potential deterrent for patients. Providers felt that an electronic
      health information system would help them better monitor patients' progress, but
      that this system would need to be integrated into existing health information
      systems. To address these potential barriers to implementing an integrated model,
      respondents recommended increasing OTP provider and clinic capacity, offering
      flexible ART dispensing options, ensuring privacy with ART dispensing, and
      harmonizing any new electronic health information systems with existing systems.
      CONCLUSIONS: An integrated methadone and ART service delivery model at the MNH
      OTP clinic could improve access to HIV care and treatment for OTP patients.
      However, specific implementation strategies must ensure that OTP providers are
      not overburdened and confidentiality of patients is maintained.

PMID- 29041951
TI  - A new bioassay for measuring the strength of IL-6/STAT3 signal inhibition by
      tocilizumab in patients with rheumatoid arthritis.
AB  - BACKGROUND: Interleukin-6 (IL-6) transduces signals via phosphorylation of STAT3
      (pSTAT3). Tocilizumab (TCZ) is an IL-6 receptor blocker, which, when administered
      intravenously every 4 weeks, efficiently ameliorates rheumatoid arthritis (RA).
      Since IL-6 signal strength varies among patients with RA, the intensity necessary
      for appropriate IL-6 signal inhibition by TCZ might vary between individuals. In
      a previous study, we have examined the clinical utility of increasing (dosing
      interval shortened to 3 weeks) and decreasing (interval extended to 5 weeks) the
      dose frequency of TCZ. However, there is currently no established method for
      accurately measuring the strength of IL-6 signal inhibition by TCZ among
      individual patients. We therefore sought to develop such an assay. METHODS: Whole
      blood samples were collected from RA patients with low disease activity (clinical
      disease activity index (CDAI) <= 10) who were treated with TCZ at dosing
      intervals of 3 weeks (3-week group, n = 10), 4 weeks (4-week group, n = 10) or 5
      weeks (5-week group, n = 10), or with methotrexate (control group, n = 10).
      Recombinant human IL-6 (0, 0.1, 1, 10, 100 ng/ml) was exogenously added to whole
      blood and the proportion of pSTAT3-positive CD4+ T cells (%pSTAT3+/CD4+) was
      measured by Phosflow cytometric analysis. RESULTS: The addition of exogenous IL-6
      increased the proportion of pSTAT3-positive CD4+ T cells in a dose-dependent
      manner in each group. Inhibition of IL-6 signaling was strongest in the 3-week
      dosing group, followed by the 4-week, 5-week and control group. Significant
      differences in %pSTAT3+/CD4+ cells were observed between dose interval groups
      when stimulated with 10 ng/ml and 100 ng/ml of IL-6. CONCLUSION: Assessment of
      the proportion of pSTAT3-positive CD4+ T cells under IL-6 stimulation is a highly
      sensitive and useful method for determining differences in the strength of IL-6
      signal inhibition in patients treated with TCZ. It is suggested that different
      TCZ treatment intervals were necessary to lower disease activity in each group of
      patients, and these findings also indicate that the IL-6 signaling pathway may
      differ in each RA patient. Our assay may support strategies for optimizing TCZ
      treatment in RA patients.

PMID- 29041953
TI  - A proposed framework for developing quality assessment tools.
AB  - BACKGROUND: Assessment of the quality of included studies is an essential
      component of any systematic review. A formal quality assessment is facilitated by
      using a structured tool. There are currently no guidelines available for
      researchers wanting to develop a new quality assessment tool. METHODS: This paper
      provides a framework for developing quality assessment tools based on our
      experiences of developing a variety of quality assessment tools for studies of
      differing designs over the last 14 years. We have also drawn on experience from
      the work of the EQUATOR Network in producing guidance for developing reporting
      guidelines. RESULTS: We do not recommend a single 'best' approach. Instead, we
      provide a general framework with suggestions as to how the different stages can
      be approached. Our proposed framework is based around three key stages: initial
      steps, tool development and dissemination. CONCLUSIONS: We recommend that anyone
      who would like to develop a new quality assessment tool follow the stages
      outlined in this paper. We hope that our proposed framework will increase the
      number of tools developed using robust methods.

PMID- 29041952
TI  - The response of muscle progenitor cells to cutaneous thermal injury.
AB  - BACKGROUND: Severe burn results in a systemic response that leads to significant
      muscle wasting. It is believed that this rapid loss in muscle mass occurs due to
      increased protein degradation combined with reduced protein synthesis.
      Alterations in the microenvironment of muscle progenitor cells may partially
      account for this pathology. The aim of this study was to ascertain the response
      of muscle progenitor cells following thermal injury in mice and to enlighten the
      cellular cascades that contribute to the muscle wasting. METHODS: C57BL/6 mice
      received a 20% total body surface area (TBSA) thermal injury. Gastrocnemius
      muscle was harvested at days 2, 7, and 14 following injury for protein and
      histological analysis. RESULTS: We observed a decrease in myofiber cross
      sectional area at 2 days post-burn. This muscle atrophy was compensated for by an
      increase in myofiber cross-sectional area at 7 and 14 days post-burn.
      Myeloperoxidase (MPO)-positive cells (neutrophils) increased significantly at 2
      days. Moreover, through Western blot analysis of two key mediators of the
      proteolytic pathway, we show there is an increase in Murf1 and NF-kappaB 2 days
      post-burn. MPO-positive cells were also positive for NF-kappaB, suggesting that
      neutrophils attain NF-kappaB activity in the muscle. Unlike inflammatory and
      proteolytic pathways, the number of Pax7-positive muscle progenitor cells
      decreased significantly 2 days post-burn. This was followed by a recovery in the
      number of Pax7-positive cells at 7 and 14 days, suggesting proliferation of
      muscle progenitors that accompanied regrowth. CONCLUSION: Our data show a
      biphasic response in the muscles of mice exposed to burn injury, with phenotypic
      characteristics of muscle atrophy at 2 days while compensation was observed later
      with a change in Pax7-positive muscle progenitor cells. Targeting muscle
      progenitors may be of therapeutic benefit in muscle wasting observed after burn
      injury.

PMID- 29041954
TI  - Combined cognitive and vocational interventions after mild to moderate traumatic
      brain injury: study protocol for a randomized controlled trial.
AB  - BACKGROUND: A considerable proportion of patients with mild to moderate traumatic
      brain injury (TBI) experience long-lasting somatic, cognitive, and emotional
      symptoms that may hamper their capacity to return to work (RTW). Although several
      studies have described medical, psychological, and work-related factors that
      predict RTW after TBI, well-controlled intervention studies regarding RTW are
      scarce. Furthermore, there has traditionally been weak collaboration among health
      related rehabilitation services, the labor and welfare sector, and workplaces.
      METHODS/DESIGN: This study protocol describes an innovative randomized controlled
      trial in which we will explore the effect of combining manualized cognitive
      rehabilitation (Compensatory Cognitive Training [CCT]) and supported employment
      (SE) on RTW and related outcomes for patients with mild to moderate TBI in real
      life competitive work settings. The study will be carried out in the southeastern
      region of Norway and thereby be performed within the Norwegian welfare system.
      Patients aged 18-60 years with mild to moderate TBI who are employed in a minimum
      50% position at the time of injury and sick-listed 50% or more for postconcussive
      symptoms 2 months postinjury will be included in the study. A comprehensive
      assessment of neurocognitive function, self-reported symptoms, emotional
      distress, coping style, and quality of life will be performed at baseline,
      immediately after CCT (3 months after inclusion), following the end of SE (6
      months after inclusion), and 12 months following study inclusion. The primary
      outcome measures are the proportion of participants who have returned to work at
      12-month follow-up and length of time until RTW, in addition to work stability as
      well as work productivity over the first year following the intervention.
      Secondary outcomes include changes in self-reported symptoms, emotional and
      cognitive function, and quality of life. Additionally, a qualitative RTW process
      evaluation focused on organizational challenges at the workplace will be
      performed. DISCUSSION: The proposed study will combine cognitive and vocational
      rehabilitation and explore the efficacy of increased cross-sectoral collaboration
      between specialized health care services and the labor and welfare system. If the
      intervention proves effective, the project will describe the cost-effectiveness
      and utility of the program and thereby provide important information for policy
      makers. In addition, knowledge about the RTW process for persons with TBI and
      their workplaces will be provided. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT03092713 . Registered on 10 March 2017.

PMID- 29041955
TI  - Pluripotent nontumorigenic multilineage differentiating stress enduring cells
      (Muse cells): a seven-year retrospective.
AB  - Multilineage differentiating stress enduring (Muse) cells, discovered in the
      spring of 2010 at Tohoku University in Sendai, Japan, were quickly recognized by
      scientists as a possible source of pluripotent cells naturally present within
      mesenchymal tissues. Muse cells normally exist in a quiescent state, singularly
      activated by severe cellular stress in vitro and in vivo. Muse cells have the
      capacity for self-renewal while maintaining pluripotent cell characteristics
      indicated by the expression of pluripotent stem cell markers. Muse cells
      differentiate into cells representative of all three germ cell layers both
      spontaneously and under media-specific induction. In contrast to embryonic stem
      and induced pluripotent stem cells, Muse cells exhibit low telomerase activity, a
      normal karyotype, and do not undergo tumorigenesis once implanted in SCID mice.
      Muse cells efficiently home into damaged tissues and differentiate into specific
      cells leading to tissue regeneration and functional recovery as described in
      different animal disease models (i.e., fulminant hepatitis, muscle degeneration,
      skin ulcers, liver cirrhosis, cerebral stroke, vitiligo, and focal segmental
      glomerulosclerosis). Circulating Muse cells have been detected in peripheral
      blood, with higher levels present in stroke patients during the acute phase.
      Furthermore, Muse cells have inherent immunomodulatory properties, which could
      contribute to tissue generation and functional repair in vivo. Genetic studies in
      Muse cells indicate a highly conserved cellular mechanism as seen in more
      primitive organisms (yeast, Saccharomyces cerevisiae, Caenorhabditis elegans,
      chlamydomonas, Torpedo californica, drosophila, etc.) in response to cellular
      stress and acute injury. This review details the molecular and cellular
      properties of Muse cells as well as their capacity for tissue repair and
      functional recovery, highlighting their potential for clinical application in
      regenerative medicine.

PMID- 29041956
TI  - Genetic sex determination of mice by simplex PCR.
AB  - BACKGROUND: Investigating fetal development in mice necessitates the
      determination of fetal sex. However, whilst the sex of adult and juvenile mice
      can be readily distinguished from anogenital distance, the sex of fetal and
      neonatal mice cannot be identified visually. Instead, genetic sex must be
      determined by PCR amplification of X chromosome genes with divergent Y chromosome
      gametologs. Existing simplex PCR methods are confounded by small size differences
      between amplicons, amplification of unexpected products, and biased amplification
      of the shorter amplicon. RESULTS: Primers were designed flanking an 84 bp
      deletion of the X-linked Rbm31x gene relative to its Y-linked gametolog Rbm31y. A
      single product was amplified from XX samples, with two products amplified from XY
      samples. Amplicons were resolved by gel electrophoresis for 20 min, with unbiased
      amplification of both products observed in XY samples. CONCLUSION: This method
      achieves rapid and unequivocal genetic sex determination of mice in low volume
      PCR reactions, reducing reagent usage and simultaneously eliminating shortcomings
      of previous methods.

PMID- 29041957
TI  - How should we give vitamin D supplementation? evaluation of the pediatricians'
      knowledge in Turkey.
AB  - BACKGROUND: We aimed to determine the knowledge and attitudes of Turkish
      pediatricians concerning vitamin D supplement. METHODS: The study was planned
      cross-sectional to be carried out between April-May 2015 in Turkey. A
      questionnaire form that determined the participants' opinions and practices
      concerning vitamin D supplement was completed via face-to-face interview.
      RESULTS: A total of 107 pediatricians (49.3%) and 110 pediatric residents (50.7%)
      participated in the study. Of the physicians, 85.2% recommended vitamin D
      supplement for all infants and children regardless of diet, 13.4% recommended for
      the infants which are solely breastfed. Vitamin D supplement is recommended at a
      dose of 400 IU/day by 88.8% of pediatricians and by 90% of pediatric residents.
      Of the pediatricians and pediatric residents, 72% and 68.2%, respectively
      commence vitamin D supplement when the newborn is 15 days old. The rates of
      recommending vitamin D supplement until the age of one and two years were higher
      among pediatricians (48.6% and 41.1%, respectively) than pediatric residents
      (40.9% and 32.7%, respectively). The rate of starting vitamin D supplement for
      fontanelle closure was significantly higher among pediatric residents (15.5%)
      than pediatricians (3.7%) (p = 0.002). It was determined that the rate of
      prescribing vitamin D supplement until fontanelle closure was higher among
      pediatric residents (18.2%) than pediatricians (0.9%). CONCLUSIONS: The present
      study suggest that the knowledge of pediatricians about recommendation of vitamin
      D needs to be enhanced by education programs in addition to free vitamin D
      supplement provided by the Ministry of Health.

PMID- 29041958
TI  - Towards a balanced view of the bacterial tree of life.
AB  - The bacterial tree of life has recently undergone significant expansion, chiefly
      from candidate phyla retrieved through genome-resolved metagenomics. Bypassing
      the need for genome availability, we present a snapshot of bacterial phylogenetic
      diversity based on the recovery of high-quality SSU rRNA gene sequences extracted
      from nearly 7000 metagenomes and all available reference genomes. We illuminate
      taxonomic richness within established bacterial phyla together with environmental
      distribution patterns, providing a revised framework for future phylogeny-driven
      sequencing efforts.

PMID- 29041959
TI  - SEED: a tool for disseminating systematic review data into Wikipedia.
AB  - Wikipedia, the free-content online encyclopaedia, contains many heavily accessed
      pages relating to healthcare. Cochrane systematic reviews contain much high-grade
      evidence but dissemination into Wikipedia has been slow. New skills are needed to
      both translate and relocate data from Cochrane reviews to implant into Wikipedia
      pages. This letter introduces a programme to greatly simplify the process of
      disseminating the summary of findings of Cochrane reviews into Wikipedia pages.

PMID- 29041961
TI  - Treatment evaluation of Wharton's jelly-derived mesenchymal stem cells using a
      chronic salpingitis model: an animal experiment.
AB  - BACKGROUND: The present study was conducted to evaluate new methods to repair the
      reproductive function of the oviduct, thereby allowing gametes to combine and
      grow in vivo under natural circumstances. METHODS: Sixty pathogen-free female New
      Zealand rabbits were divided into three groups: a wild-type group, an untreated
      control group, and a treatment group. Disposable sterile newborn sputum suction
      tubes were inserted into the urogenital tract to instill an Escherichia coli
      suspension into the uterine cavity to establish the chronic salpingitis model.
      Wharton's jelly-derived mesenchymal stem cells (WJMSCs) or normal saline were
      used to treat this infection via different methods. The therapeutic effect was
      assessed by evaluating morphology, inflammatory factors, proteinology, and
      pregnancy outcomes. RESULTS: Oviducts of New Zealand rabbits in the untreated
      control group showed structural failure and abnormal supermicrostructure of
      epithelial cells. WJMSCs could partially repair the structure and
      supermicrostructure of the tubal epithelium. The concentration of tumor necrosis
      factor (TNF)-alpha in the untreated control group was significantly higher than
      that in the wild-type group (P = 0.015). The concentration of TNF-alpha in the
      local treatment group was significantly lower than that in the untreated control
      group (P = 0.011). The expression of oviductal glycoprotein (OVGP) and OVGP mRNA
      in the wild-type group was significantly higher than those in the untreated
      control group (P = 0.024 and P = 0.013, respectively). The litter size of the
      treatment group was 2 +/- 2.39 kits, which was higher than that of the untreated
      control group (P = 0.035). CONCLUSION: Chronic inflammation can destroy the
      structure of the oviduct and the supermicrostructure of epithelial cells as well
      as leading to infertility. WJMSC transplantation therapy in rabbits with chronic
      salpingitis partially restored fertility. WJMSCs also repaired the structure of
      the tubal epithelium subjected to chronic inflammation, decreased the level of
      inflammatory factors, and partially restored the secretion level of OVGP.

PMID- 29041960
TI  - Substantial contribution of genetic variation in the expression of transcription
      factors to phenotypic variation revealed by eRD-GWAS.
AB  - BACKGROUND: There are significant limitations in existing methods for the genome
      wide identification of genes whose expression patterns affect traits. RESULTS:
      The transcriptomes of five tissues from 27 genetically diverse maize inbred lines
      were deeply sequenced to identify genes exhibiting high and low levels of
      expression variation across tissues or genotypes. Transcription factors are
      enriched among genes with the most variation in expression across tissues, as
      well as among genes with higher-than-median levels of variation in expression
      across genotypes. In contrast, transcription factors are depleted among genes
      whose expression is either highly stable or highly variable across genotypes. We
      developed a Bayesian-based method for genome-wide association studies (GWAS) in
      which RNA-seq-based measures of transcript accumulation are used as explanatory
      variables (eRD-GWAS). The ability of eRD-GWAS to identify true associations
      between gene expression variation and phenotypic diversity is supported by
      analyses of RNA co-expression networks, protein-protein interaction networks, and
      gene regulatory networks. Genes associated with 13 traits were identified using
      eRD-GWAS on a panel of 369 maize inbred lines. Predicted functions of many of the
      resulting trait-associated genes are consistent with the analyzed traits.
      Importantly, transcription factors are significantly enriched among trait
      associated genes identified with eRD-GWAS. CONCLUSIONS: eRD-GWAS is a powerful
      tool for associating genes with traits and is complementary to SNP-based GWAS.
      Our eRD-GWAS results are consistent with the hypothesis that genetic variation in
      transcription factor expression contributes substantially to phenotypic
      diversity.

PMID- 29041962
TI  - Comparative assessment of An. gambiae and An. stephensi mosquitoes to determine
      transmission-reducing activity of antibodies against P. falciparum sexual stage
      antigens.
AB  - BACKGROUND: With the increasing interest in vaccines to interrupt malaria
      transmission, there is a demand for harmonization of current methods to assess
      Plasmodium transmission in laboratory settings. Potential vaccine candidates are
      currently tested in the standard membrane feeding assay (SMFA) that commonly
      relies on Anopheles stephensi mosquitoes. Other mosquito species including
      Anopheles gambiae are the dominant malaria vectors for Plasmodium falciparum in
      sub-Saharan Africa. METHODS: Using human serum and monoclonal pre-fertilization
      (anti-Pfs48/45) and post-fertilization (anti-Pfs25) antibodies known to
      effectively inhibit sporogony, we directly compared SMFA based estimates of
      transmission-reducing activity (TRA) for An. stephensi and An. gambiae
      mosquitoes. RESULTS: In the absence of transmission-reducing antibodies, average
      numbers of oocysts were similar between An. gambiae and An. stephensi. Antibody
      mediated TRA was strongly correlated between both mosquito species, and absolute
      TRA estimates for pre-fertilisation monoclonal antibodies (mAb) showed no
      significant difference between the two species. TRA estimates for IgG of
      naturally exposed individuals and partially effective concentrations of anti
      Pfs25 mAb were higher for An. stephensi than for An. gambiae. CONCLUSION: Our
      findings support the use of An. stephensi in the SMFA for target prioritization.
      As a vaccine moves through product development, better estimates of TRA and
      transmission-blocking activity (TBA) may need to be obtained in epidemiologically
      relevant parasite-species combination.

PMID- 29041964
TI  - Olfactive stimulation interventions for managing procedural pain in preterm and
      full-term neonates: a systematic review protocol.
AB  - BACKGROUND: While hospitalized in the NICU, preterm neonates undergo many painful
      procedures. This may be the same for full-term neonates when longer
      hospitalization is required. Untreated and repeated pain has short-term as well
      as long-term consequences for these neonates. Pharmacological pain management
      methods have many limitations in their applications for both preterm and full
      term neonates. A combination of different non-pharmacological methods is
      recommended for pain management. The effect of olfactive stimulation as a non
      pharmacological pain management method was investigated by a few studies in the
      past years with premature and term neonates, but no systematic review has been
      conducted. The objective of this systematic review is to evaluate the effect of
      olfactive stimulation intervention on the pain response of preterm and full-term
      neonates during painful procedures. METHODS: An electronic search will be
      conducted in various databases such as PubMed (1946 to date), MEDLINE (1946 to
      date), CINAHL (1981 to date), Embase (1947 to date), PsycINFO (1806 to date), Web
      of Science (1945 to date), CENTRAL and Scopus (1960 to date), and Proquest,
      without restriction for the year of publication. Only studies published in
      English or French will be included. The search will be conducted using the
      following three concepts: pain, odors, and neonates. Selection of articles, data
      extraction, and assessment of risk of bias will be conducted by two independent
      researchers. A third researcher will intervene in case of disagreement. According
      to the availability of studies and data homogeneity, the results will be combined
      to perform a meta-analysis, or they will be described by a narrative synthesis.
      DISCUSSION: This systematic review will provide light on the current state of
      knowledge on the effectiveness of olfactive stimulation interventions for
      managing pain in preterm and full-term neonates. This review will guide clinical
      practice as well as research to improve preterm and full-term neonates' pain
      management and prevent short-term and long-term complications caused by pain.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017058021.

PMID- 29041963
TI  - Is gout a risk equivalent to diabetes for stroke and myocardial infarction? A
      retrospective claims database study.
AB  - BACKGROUND: Gout is a risk factor for cardiovascular disease, but associations
      with specific cardiovascular outcomes, myocardial infarction (MI), and stroke are
      unclear. Our objective in the present study was to assess whether gout is as
      strong a risk factor as diabetes mellitus (DM) for incident MI and incident
      stroke. METHODS: In this retrospective study, we used U.S. claims data from 2007
      to 2010 that included a mix of private and public health plans. Four mutually
      exclusive cohorts were identified: (1) DM only, (2) gout only, (3) gout and DM,
      and (4) neither gout nor DM. Outcomes were acute MI or stroke with
      hospitalization. We compared the age- and sex-specific rates of incident MI and
      stroke across the four cohorts and assessed multivariable-adjusted HRs. RESULTS:
      In this study, 232,592 patients had DM, 71,755 had gout, 23,261 had both, and
      1,010,893 had neither. The incidence of acute MI was lowest in patients with
      neither gout nor DM, followed by patients with gout alone, DM alone, and both.
      Among men >80 years of age, the respective rates/1000 person-years were 14.6,
      25.4, 27.7, and 37.4. Similar trends were noted for stroke and in women. Compared
      with DM only, gout was associated with a significantly lower adjusted HR of
      incident MI (HR 0.81, 95% CI 0.76-0.87) but a similar risk of stroke (HR 1.02,
      95% CI 0.95-1.10). Compared with patients with DM only, patients with both gout
      and DM had higher HRs for incident MI and stroke (respectively, HR 1.35, 95% CI
      1.25-1.47; HR 1.42, 95% CI 1.29-1.56). CONCLUSIONS: Gout is a risk equivalent to
      DM for incident stroke but not for incident MI. Having both gout and DM confers
      incremental risk compared with DM alone for both incident MI and stroke.

PMID- 29041966
TI  - Correction to: Obesity, change of body mass index and subsequent physical and
      mental health functioning: a 12-year follow-up study among ageing employees.

PMID- 29041965
TI  - Enrichment allows identification of diverse, rare elements in metagenomic
      resistome-virulome sequencing.
AB  - BACKGROUND: Shotgun metagenomic sequencing is increasingly utilized as a tool to
      evaluate ecological-level dynamics of antimicrobial resistance and virulence, in
      conjunction with microbiome analysis. Interest in use of this method for
      environmental surveillance of antimicrobial resistance and pathogenic
      microorganisms is also increasing. In published metagenomic datasets, the total
      of all resistance- and virulence-related sequences accounts for < 1% of all
      sequenced DNA, leading to limitations in detection of low-abundance resistome
      virulome elements. This study describes the extent and composition of the low
      abundance portion of the resistome-virulome, using a bait-capture and enrichment
      system that incorporates unique molecular indices to count DNA molecules and
      correct for enrichment bias. RESULTS: The use of the bait-capture and enrichment
      system significantly increased on-target sequencing of the resistome-virulome,
      enabling detection of an additional 1441 gene accessions and revealing a low
      abundance portion of the resistome-virulome that was more diverse and
      compositionally different than that detected by more traditional metagenomic
      assays. The low-abundance portion of the resistome-virulome also contained
      resistance genes with public health importance, such as extended-spectrum
      betalactamases, that were not detected using traditional shotgun metagenomic
      sequencing. In addition, the use of the bait-capture and enrichment system
      enabled identification of rare resistance gene haplotypes that were used to
      discriminate between sample origins. CONCLUSIONS: These results demonstrate that
      the rare resistome-virulome contains valuable and unique information that can be
      utilized for both surveillance and population genetic investigations of
      resistance. Access to the rare resistome-virulome using the bait-capture and
      enrichment system validated in this study can greatly advance our understanding
      of microbiome-resistome dynamics.

PMID- 29041967
TI  - Microparticles from patients with systemic lupus erythematosus induce production
      of reactive oxygen species and degranulation of polymorphonuclear leukocytes.
AB  - BACKGROUND: The interaction of circulating microparticles (MPs) with immune cells
      in systemic lupus erythematosus (SLE) is sparsely investigated. We examined the
      ability of MPs from SLE patients to induce production of reactive oxygen species
      (ROS) and degranulation of polymorphonuclear leukocytes (PMNs). METHODS: Plasma
      MPs, leukocytes and sera isolated from 20 SLE patients and 10 healthy controls
      were mixed in different combinations, with or without lipopolysaccharide (LPS),
      and incubated for 30 min. Dihydrorhodamine 123 was used to measure ROS production
      by flow cytometry. The ability of immunoglobulin G (IgG) isolated from five SLE
      patients to increase MP-induced production of ROS by PMNs was tested. Cell
      supernatants were analysed for content of primary, secondary and tertiary granule
      components by Luminex assays. RESULTS: MPs from SLE patients promoted ROS
      production by PMNs, and enhanced LPS-induced ROS production and release of
      primary granules by PMNs, when added to samples of autologous leukocytes and
      serum. In a similar autologous setting, MPs from healthy controls enhanced LPS
      induced ROS production by PMNs. When leukocytes from a healthy control were
      stimulated with autologous MPs in the presence of various sera, SLE patient serum
      promoted ROS production and release of primary and secondary granules by PMNs. A
      role for antibodies in this respect was indicated by the observation that
      supplementation of normal serum with IgG from SLE patients promoted MP-induced
      ROS production by healthy PMNs. Moreover, when various MPs were incubated with
      leukocytes and serum from a healthy control, patient-derived MPs induced more ROS
      production by PMNs than did healthy control-derived MPs. CONCLUSIONS: SLE
      patients display increased ROS production and degranulation by PMNs in response
      to MPs, which partly depends on serum components, including antibodies, MP
      properties and hyper-responsiveness of the PMNs per se.

PMID- 29041968
TI  - Dynamic changes of oligomeric amyloid beta levels in plasma induced by spiked
      synthetic Abeta42.
AB  - BACKGROUND: A reliable blood-based assay is required to properly diagnose and
      monitor Alzheimer's disease (AD). Many attempts have been made to develop such a
      diagnostic tool by measuring amyloid-beta oligomers (AbetaOs) in the blood, but
      none have been successful in terms of method reliability. We present a multimer
      detection system (MDS), initially developed for the detection of prion oligomers
      in the blood, to detect AbetaOs. METHODS: To characterize Abeta in the blood,
      plasma was spiked with synthetic amyloid-beta (Abeta) and incubated over time.
      Then, the MDS was used to monitor the dynamic changes of AbetaO levels in the
      plasma. RESULTS: Increasing concentrations of AbetaOs were observed in the plasma
      of patients with AD but not in the plasma of normal control subjects. The plasma
      from patients with AD (n = 27) was differentiated from that of the age-matched
      normal control subjects (n = 144) with a sensitivity of 83.3% and a specificity
      of 90.0%. CONCLUSIONS: Synthetic Abeta spiked into the blood plasma of patients
      with AD, but that of not elderly normal control subjects, induced dynamic changes
      in the formation of AbetaOs over time. AbetaOs were detected by the MDS, which is
      a useful blood-based assay with high sensitivity and specificity for AD
      diagnosis.

PMID- 29041970
TI  - Comparison of the efficacy of static versus articular spacers in two-stage
      revision surgery for the treatment of infection following total knee
      arthroplasty: a meta-analysis.
AB  - BACKGROUND: The aim of this study was to compare the outcomes of static versus
      articular spacers in two-stage reimplantation for the treatment of infected total
      knee arthroplasty (TKA). METHODS: The literature regarding the articulating and
      static spacers for treating infected TKA were searched in PubMed, Embase,
      Cochrane Library, Chinese Periodical Full-Text Database of CNKI, and Wanfang
      database. Data were extracted according to the inclusion and exclusion criteria
      and analyzed by Review Manager 5.3. RESULTS: Ten studies were included to this
      meta-analysis (nine retrospective studies, one prospective study) according to
      the principle of PICOS. There was no significant difference regarding the
      eradication rate (P = 0.28) and the American Knee Society knee score (KSS) pain
      score (P = 0.11) between the articulating and static spacers in the two-stage
      revision surgery. There was no significant difference regarding quadriceps
      femoroplasty and tibial tubercle osteotomy between the two groups (P = 0.50). The
      knee range of motion (ROM), Hospital for Special Surgery (HSS) score, and KSS
      function score in the articulating group were significantly higher than those in
      the static group (P < 0.00001). CONCLUSION: Articulating spacers can provide
      better ROM and knee function scores after revision surgery when compared to
      static spacer while not compromising the infection eradication rate, soft tissue
      contracture during exclusion period, and knee pain scores.

PMID- 29041969
TI  - Glial cells are functionally impaired in juvenile neuronal ceroid lipofuscinosis
      and detrimental to neurons.
AB  - The neuronal ceroid lipofuscinoses (NCLs or Batten disease) are a group of
      inherited, fatal neurodegenerative disorders of childhood. In these disorders,
      glial (microglial and astrocyte) activation typically occurs early in disease
      progression and predicts where neuron loss subsequently occurs. We have found
      that in the most common juvenile form of NCL (CLN3 disease or JNCL) this glial
      response is less pronounced in both mouse models and human autopsy material, with
      the morphological transformation of both astrocytes and microglia severely
      attenuated or delayed. To investigate their properties, we isolated glia and
      neurons from Cln3-deficient mice and studied their basic biology in culture. Upon
      stimulation, both Cln3-deficient astrocytes and microglia also showed an
      attenuated ability to transform morphologically, and an altered protein secretion
      profile. These defects were more pronounced in astrocytes, including the reduced
      secretion of a range of neuroprotective factors, mitogens, chemokines and
      cytokines, in addition to impaired calcium signalling and glutamate clearance.
      Cln3-deficient neurons also displayed an abnormal organization of their neurites.
      Most importantly, using a co-culture system, Cln3-deficient astrocytes and
      microglia had a negative impact on the survival and morphology of both Cln3
      deficient and wildtype neurons, but these effects were largely reversed by
      growing mutant neurons with healthy glia. These data provide evidence that CLN3
      disease astrocytes are functionally compromised. Together with microglia, they
      may play an active role in neuron loss in this disorder and can be considered as
      potential targets for therapeutic interventions.

PMID- 29041971
TI  - Finnish physicians' stress related to information systems keeps increasing: a
      longitudinal three-wave survey study.
AB  - BACKGROUND: Poorly functioning, time-consuming, and inadequate information
      systems are among the most important work-related psychosocial factors causing
      stress in physicians. The present study examined the trend in the perceived
      stress that was related to information systems (SRIS) among Finnish physicians
      during a nine-year follow-up. In addition, we examined the associations of
      gender, age, employment sector, specialization status, leadership position, on
      call burden, and time pressure with SRIS change and levels. METHODS: A
      longitudinal design with three survey data collection waves (2006, 2010 and 2015)
      based on a random sample of Finnish physicians in 2006 was used. The study sample
      included 1095 physicians (62.3% women, mean age 54.4 years) who provided data on
      SRIS in every wave. GLM repeated measures analyses were used to examine the
      associations between independent variables and the SRIS trend during the years
      2006, 2010, and 2015. RESULTS: SRIS increased during the study period. The
      estimated marginal mean of SRIS in 2006 was 2.80 (95% CI = 2.68-2.92) and the
      mean increase was 0.46 (95% CI = 0.30-0.61) points from 2006 to 2010 and 0.25
      (95% CI = 0.11-0.39) points from 2010 to 2015. Moreover, our results show that
      the increase was most pronounced in primary care, whereas in hospitals SRIS did
      not increase between 2010 and 2015. SRIS increased more among those in a
      leadership position. On-call duties and high time-pressures were associated with
      higher SRIS levels during all waves. CONCLUSIONS: Changing, difficult, and poorly
      functioning information systems (IS) are a prominent source of stress among
      Finnish physicians and this perceived stress continues to increase. Organizations
      should implement arrangements to ease stress stemming from IS especially for
      those with a high workload and on-call or leadership duties. To decrease IS
      related stress, it would be important to study in more detail the main IS factors
      that contribute to SRIS. Earlier studies indicate that the usability and
      stability of information systems as well as end-user involvement in system
      development and work-procedure planning may be significant factors.

PMID- 29041972
TI  - Understanding the preference for homebirth; an exploration of key barriers to
      facility delivery in rural Tanzania.
AB  - BACKGROUND: There is limited information on the effect of expectant parents'
      socio-cultural perceptions and practices on the use of skilled birth attendants
      (SBAs) in rural Tanzania. The purpose of this study was to explore the socio
      cultural barriers to health facility birth and SBA among parents choosing home
      birth in rural Tanzania, specifically in the Rukwa Region. METHODS: This study
      used a descriptive exploratory methodology. Purposive sampling was used to
      recruit study participants for both in-depth interviews (IDIs) and focused group
      discussions (FGDs). Qualitative research methods, including FGDs and IDIs, were
      utilized in data collection. The respondents were men and women whose youngest
      child had been born at home within the prior 12 months. A thematic approach was
      used for data analysis. RESULTS: The main themes that emerged regarding barriers
      to the use of health facility were 1) limited decision-making by men on place of
      delivery; 2) low risk perception by men and its interference with health facility
      birth; 3) men's limited resource mobilization for health facility birth and 4)
      females' perceptions that pregnancy and childbirth are low-risk events.
      CONCLUSION: This qualitative study demonstrates that apart from well-documented
      structural barriers to skilled birth attendance in rural Tanzania, the low risk
      perception among both men and women plays a substantial role. The low risk
      perception among both men and women affects the use of SBAs in two ways. First,
      women become negligent and take risk of delivering at home. Second, male partners
      do not seriously mobilize resources for health facility childbirth. These
      findings reinforce the urgent need to implement creative programs to increase
      genuine male participation in facilitation of health facility childbirth.

PMID- 29041973
TI  - The establishment and application of preimplantation genetic haplotyping in
      embryo diagnosis for reciprocal and Robertsonian translocation carriers.
AB  - BACKGROUND: Preimplantation genetic diagnosis (PGD) is now widely used to select
      embryos free of chromosomal copy number variations (CNV) from chromosome balanced
      translocation carriers. However, it remains a difficulty to distinguish in
      embryos between balanced and structurally normal chromosomes efficiently.
      METHODS: For this purpose, genome wide preimplantation genetic haplotyping (PGH)
      analysis was utilized based on single nucleotide polymorphism (SNP) microarray.
      SNPs that are heterozygous in the carrier and, homozygous in the carrier's
      partner and carrier's family member are defined as informative SNPs. The
      haplotypes including the breakpoint regions, the whole chromosomes involved in
      the translocation and the corresponding homologous chromosomes are established
      with these informative SNPs in the couple, reference and embryos. In order to
      perform this analysis, a reference either a translocation carrier's family member
      or one unbalanced embryo is required. The positions of translocation breakpoints
      are identified by molecular karyotypes of unbalanced embryos. The recombination
      of breakpoint regions in embryos could be identified. RESULTS: Eleven
      translocation families were enrolled. 68 blastocysts were analyzed, in which 42
      were unbalanced or aneuploid and the other 26 were balanced or normal
      chromosomes. Thirteen embryos were transferred back to patients. Prenatal
      cytogenetic analysis of amniotic fluid cells was performed. The results predicted
      by PGH and karyotypes were totally consistent. CONCLUSIONS: With the successful
      clinical application, we demonstrate that PGH was a simple, efficient, and
      popularized method to distinguish between balanced and structurally normal
      chromosome embryos.

PMID- 29041974
TI  - Postoperative functional status in patients with supratentorial superficial low
      grade glioma.
AB  - BACKGROUND: We investigated the functional status of adult supratentorial
      superficial low-grade glioma (ASS-LGG) after surgery and analyzed its relevant
      factors to guide the therapeutic strategy and improve the life quality of these
      patients. METHODS: Clinical materials from January 2008 to December 2010 in 104
      adults with ASS-LGG were analyzed retrospectively. The follow-up period ranged
      from 6 months to 1.5 years. The logistic regression was used to evaluate the
      preoperative and postoperative variation of functional status in patients to
      disclose the relevant factors affecting postoperative functional status, such as
      age, gender, the duration of symptom, size and location of the tumor, hemisphere,
      resection degree, and tumor pathologic grade and preoperative Karnofsky
      performance status (Pre-KPS). RESULTS: Four out of nine candidate factors are
      related to the postoperative functional status. They are age less than 40 years,
      the size of tumor less than 5 cm in diameter, tumor located in the right
      hemisphere, and limited resection of tumor in the eloquent area. CONCLUSIONS: It
      seems more meaningful to evaluate the functional status of the patients with ASS
      LGG on the basis of these clinical features, involving age, tumor size, location,
      and extent of resection.

PMID- 29041975
TI  - Extreme precipitation and emergency room visits for influenza in Massachusetts: a
      case-crossover analysis.
AB  - BACKGROUND: Influenza peaks during the wintertime in temperate regions and during
      the annual rainy season in tropical regions - however reasons for the observed
      differences in disease ecology are poorly understood. We hypothesize that
      episodes of extreme precipitation also result in increased influenza in the
      Northeastern United States, but this association is not readily apparent, as no
      defined 'rainy season' occurs. Our objective was to evaluate the association
      between extreme precipitation (>= 99th percentile) events and risk of emergency
      room (ER) visit for influenza in Massachusetts during 2002-2008. METHODS: A case
      crossover analysis of extreme precipitation events and influenza ER visits was
      conducted using hospital administrative data including patient town of residence,
      date of visit, age, sex, and associated diagnostic codes. Daily precipitation
      estimates were generated for each town based upon data from the National Oceanic
      and Atmospheric Administration. Odds ratio (OR) and 95% confidence intervals (CI)
      for associations between extreme precipitation and ER visits for influenza were
      estimated using conditional logistic regression. RESULTS: Extreme precipitation
      events were associated with an OR = 1.23 (95%CI: 1.16, 1.30) for ER visits for
      influenza at lag days 0-6. There was significant effect modification by race,
      with the strongest association observed among Blacks (OR = 1.48 (1.30, 1.68)).
      CONCLUSIONS: We observed a positive association between extreme precipitation
      events and ER visits for influenza, particularly among Blacks. Our results
      suggest that influenza is associated with extreme precipitation in a temperate
      area; this association could be a result of disease ecology, behavioral changes
      such as indoor crowding, or both. Extreme precipitation events are expected to
      increase in the Northeastern United States as climate change progresses.
      Additional research exploring the basis of this association can inform potential
      interventions for extreme weather events and influenza transmission.

PMID- 29041976
TI  - Human pupillary light reflex during successive irradiation with 1-ms blue- and
      green-pulsed light.
AB  - BACKGROUND: In the human retina, the contribution of intrinsically photosensitive
      retinal ganglion cells (ipRGCs) to the regulation of the pupillary response
      remains poorly understood. The objective of the current study was to determine
      the response dynamics of the pupillary light reflex to short, successive pulses
      of light. In order to better assess the roles of ipRGCs and cones, we used pulses
      of blue and green light. METHODS: Each participant was exposed to 1-ms blue (466
      nm) and/or green (527 nm) light pulses simultaneously or separately, with inter
      stimulus intervals (ISIs) of 0, 250, 500, 750, or 1000 ms. Pupil diameter was
      measured using an infrared camera system. RESULTS: We found that human pupillary
      light responses during simultaneous irradiation or successive irradiation with
      ISIs <= 250 ms were equivalent, though successive irradiation of blue- and green
      pulsed light with ISIs >= 500 ms induced markedly increased pupillary
      constriction. CONCLUSIONS: We propose that this result may be related to cell
      hyperpolarization that occurs in the retina just after the first light stimulus
      is turned off, with the threshold for this effect being between 250 and 500 ms in
      the human retina.

PMID- 29041977
TI  - Perceptions of and barriers to family planning services in the poorest regions of
      Chiapas, Mexico: a qualitative study of men, women, and adolescents.
AB  - BACKGROUND: In the poorest regions of Chiapas, Mexico, 50.2% of women in need of
      contraceptives do not use any modern method. A qualitative study was needed to
      design effective and culturally appropriate interventions. METHODS: We used
      purposive maximum-variation sampling to select eight municipalities with a high
      proportion of residents in the poorest wealth quintile, including urban, rural,
      indigenous, and non-indigenous communities. We conducted 44 focus group
      discussions with 292 women, adolescent women, and men using semi-structured topic
      guides. We analyzed the data through recursive abstraction. RESULTS: There were
      intergenerational and cultural gaps in the acceptability of family planning, and
      in some communities family planning use was greatly limited by gender roles and
      religious objections to contraception. Men strongly influenced family planning
      choices in many households, but were largely unreached by outreach and education
      programs due to their work hours. Respondents were aware of many modern methods
      but often lacked deeper knowledge and held misconceptions about long-term
      fertility risks posed by some hormonal methods. Acute physical side effects also
      dissuaded use. The implant was a new and highly acceptable method due to ease of
      use, low upkeep, and minimal side effects; however, it was perceived as subject
      to stock-outs. Adolescent women reported being refused services at health
      facilities and requested more reproductive health information from their parents
      and schools. Mass and social media are growing sources of reproductive health
      information. CONCLUSIONS: Our study identifies a number of barriers to family
      planning that have yet to be adequately addressed by existing programs in
      Chiapas' poorest regions, and calls for reinvigorated efforts to provide
      effective, acceptable, and culturally appropriate interventions for these
      communities.

PMID- 29041978
TI  - Linc-RoR promotes MAPK/ERK signaling and confers estrogen-independent growth of
      breast cancer.
AB  - BACKGROUND: The conversion from estrogen-dependent to estrogen-independent state
      of ER+ breast cancer cells is the key step to promote resistance to endocrine
      therapies. Although the crucial role of MAPK/ERK signaling pathway in estrogen
      independent breast cancer cell growth is well established, the underlying
      mechanism is not fully understood. METHODS: In this study, we profiled lncRNA
      expression against a focused group of lncRNAs selected from lncRNA database.
      CRISPR/Cas9 was employed to knockout (KO) linc-RoR in MCF-7 cells, while rescue
      experiments were carried out to re-express linc-RoR in KO cells. Colony formation
      and MTT assays were used to examine the role of linc-RoR in estrogen-independent
      growth and tamoxifen resistance. Western blot and qRT-PCR were used to determine
      the change of protein and lncRNA levels, respectively. The expression of DUSP7 in
      clinical specimens was downloaded from Oncomine ( www.oncomine.org ) and the
      dataset from Kaplan-Meier Plotter ( http://kmplot.com ) was used to analyze the
      clinical outcomes in relation to DUSP7. RESULTS: We identified that linc-RoR
      functions as an onco-lncRNA to promote estrogen-independent growth of ER+ breast
      cancer. Under estrogen deprivation, linc-RoR causes the upregulation of
      phosphorylated MAPK/ERK pathway which in turn activates ER signaling. Knockout of
      linc-RoR abrogates estrogen deprivation-induced ERK activation as well as ER
      phosphorylation, whereas re-expression of linc-RoR restores all above phenotypes.
      Moreover, we show that the ERK-specific phosphatase Dual Specificity Phosphatase
      7 (DUSP7), also known as MKP-X, is involved in linc-RoR KO-induced repression of
      MAPK/ERK signaling. Interestingly, linc-RoR KO increases the protein stability of
      DUSP7, resulting in repression of ERK phosphorylation. Clinical data analysis
      reveal that DUSP7 expression is lower in ER+ breast cancer samples than that in
      ER- breast cancer. Moreover, downregulation of DUSP7 expression is associated
      with poor patient survival. CONCLUSION: Taken together, these results suggest
      that linc-RoR promotes estrogen-independent growth and activation of MAPK/ERK
      pathway of breast cancer cells by regulating the ERK-specific phosphatase DUSP7.
      Thus, this study might help not only in establishing a role for linc-RoR in
      estrogen-independent and tamoxifen resistance of ER+ breast cancer, but also
      suggesting a link between linc-RoR and MAPK/ERK pathway.

PMID- 29041979
TI  - Methotrexate and anti-tumor necrosis factor treatment improves endothelial
      function in patients with inflammatory arthritis.
AB  - BACKGROUND: Inflammatory arthritis (IA), including rheumatoid arthritis (RA),
      ankylosing spondylitis (AS) and psoriatic arthritis (PsA), leads to increased
      cardiovascular disease occurrence probably due to atherosclerosis. One of the
      first stages in atherogenesis is endothelial dysfunction (ED). Therefore, we
      aimed to compare endothelial function (EF) in patients with IA, and to examine
      the effects of methotrexate (MTX) monotherapy and antitumor necrosis factor (anti
      TNF) treatment with or without MTX comedication (anti-TNF +/- MTX) on EF.
      METHODS: From the PSARA observational study, all patients with RA (n = 64), PsA
      (n = 29), and AS (n = 20) were evaluated for EF. In patients with ED at baseline
      (n = 40), we evaluated changes in the Reactive Hyperemic Index (RHI) after 6
      weeks and 6 months of antirheumatic therapy. RESULTS: In IA patients with ED, RHI
      significantly improved after 6 weeks (p < 0.001) and 6 months (p < 0.001) of
      treatment, independent of changes in disease activity parameters. After 6 months,
      RHI had improved more in the MTX group than in the anti-TNF +/- MTX group, and
      the difference remained statistically significant after adjustments for potential
      confounders. Among patients with active RA, AS, and PsA, those with AS appeared
      to have the worst endothelial function, although they were the youngest.
      CONCLUSION: Treatment with MTX and anti-TNF +/- MTX was associated with a
      relatively fast improvement of EF in IA patients with ED, independent of change
      in disease activity. Therefore, modes of action other than the anti-inflammatory
      effect may contribute to the EF improvement. After 6 months, the EF improvement
      was more pronounced in the MTX group than in the anti-TNF +/- MTX group. TRIAL
      REGISTRATION: Clinicaltrials, NCT00902005 . Registered on 13 May 2009.

PMID- 29041980
TI  - Comparison of the clinical effectiveness of US grading scoring system vs MRI in
      the diagnosis of early rheumatoid arthritis (RA).
AB  - BACKGROUND: As an irreversible disease, a treatment delay can negatively affect
      treatment response in rheumatoid arthritis (RA). Ultrasound and MRI have played
      an important role in assessing disease progression and response to treatment in
      RA for many years. The present study was designed to compare the diagnostic
      efficacy of ultrasound grading and MRI in early RA. METHODS: In this
      retrospective study, 62 early RA patients within 12 months of symptom onset were
      included. DAS28, rheumatoid factor (RF), CRP, ESR, and anti-cyclic citrullinated
      peptide antibody (CCP) of the patients were measured. Bilateral hand joints and
      wrists were examined by ultrasonography (US) and MRI; diagnosis outcome was
      compared. Relationship between DAS28 scores, laboratory parameters, and
      ultrasound findings were analyzed. RESULTS: Ultrasound and MRI had an equivalent
      diagnosis value in synovitis, joint effusion, and tenosynovitis. The detection
      rate of synovitis, arthroedema, and tenosynovitis on ultrasound and MRI was very
      close (P > 0.05). The detection rate of bone erosion was lower in ultrasonography
      than that in MRI (P < 0.05). There were significant differences between power
      Doppler ultrasonography (PDUS) and gray-scale ultrasonography (GSUS) in the
      diagnosis of synovitis (chi 2 = 3.92, P < 0.05); the sensitivity of GSUS was
      better than that of PDUS (P < 0.05). PDUS was positively correlated with DAS28,
      ESR, CRP, and CCP (P < 0.01), but not correlated with RF and disease duration (P
      > 0.05). GSUS was positively correlated with RF and CRP (P < 0.01), but not
      correlated with DAS28, CCP, ESR, and disease duration (P > 0.05). Bone erosion
      was positively correlated with disease duration, CCP, and RF (P < 0.01) and was
      not correlated with DAS28, ESR, and CRP (P > 0.05). CONCLUSION: Ultrasonography
      has a high reliability in the diagnosis of early RA in synovitis, joint effusion,
      tenosynovitis, and bone erosion. Ultrasonography and clinical and laboratory
      parameters had a great correlativity. Both ultrasound and MRI are effective
      techniques. In view of the advantages of low cost and convenience, ultrasound may
      be a better choice during early RA diagnosis.

PMID- 29041981
TI  - An integrated conceptual framework for evaluating and improving 'understanding'
      in informed consent.
AB  - BACKGROUND: The development of understandable informed consent (IC) documents has
      proven to be one of the most important challenges in research with humans as well
      as in healthcare settings. Therefore, evaluating and improving understanding has
      been of increasing interest for empirical research on IC. However, several
      conceptual and practical challenges for the development of understandable IC
      documents remain unresolved. METHODS: In this paper, we will outline and
      systematize some of these challenges. On the basis of our own experiences in
      empirical user testing of IC documents as well as the relevant literature on
      understanding in IC, we propose an integrated conceptual model for the
      development of understandable IC documents. RESULTS: The proposed conceptual
      model integrates different methods for the participatory improvement of written
      information, including IC, as well as quantitative methods for measuring
      understanding in IC. CONCLUSIONS: In most IC processes, understandable written
      information is an important prerequisite for valid IC. To improve the quality of
      IC documents, a conceptual model for participatory procedures of testing,
      revising, and retesting can be applied. However, the model presented in this
      paper needs further theoretical and empirical elaboration and clarification of
      several conceptual and practical challenges.

PMID- 29041982
TI  - Costs related to cardiac arrest management: a systematic review protocol.
AB  - BACKGROUND: Each year, about 500,000 people suffer a cardiac arrest (either out
      of-hospital or in-hospital) in the USA. Although significant improvements in
      survival have occurred through the implementation of complex high-quality
      protocols of care, global costs related to such management are not clearly
      described. METHODS: We will undertake a systematic review of the published
      literature on costs related to the acute phase of cardiac arrest management (from
      collapse to hospital discharge). The search will cover the period 1991 to
      present, and we will include studies written in English or in French involving
      patients with cardiac arrest of all ages, settings (in- and out-of-hospital
      arrest), countries, and etiology (including traumatic). The primary outcome will
      include estimates of costs related to cardiac arrest patients' management in
      various categories (e.g., resuscitation process, in-hospital management as well
      as rehabilitation and long-term care facilities) and perspectives (e.g.,
      hospital, societal, or third-payer perspective). Study selection will follow the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      guidelines, and data quality will be assessed by questions adapted from the
      Drummond economic evaluation checklist. DISCUSSION: This review will provide an
      estimate of costs related to cardiac arrest management according to the different
      components of such a management as well as total costs. SYSTEMATIC REVIEW
      REGISTRATION: International Prospective Register of Systematic Reviews PROSPERO
      CRD42016046993.

PMID- 29041983
TI  - PAK5-mediated phosphorylation and nuclear translocation of NF-kappaB-p65 promotes
      breast cancer cell proliferation in vitro and in vivo.
AB  - BACKGROUND: Abnormal proliferation is significantly associated with the promotion
      of malignant tumor. Growing evidence suggest that the signal pathways of
      p21cdc42/rac1-activated kinase 5 (PAK5) have been found in various tumor
      progression, however, the role of PAK5 in breast cancer remains largely unclear.
      METHODS: We evaluated PAK5 and p65 staining in breast cancer tissues (BCTs) and
      paired non-cancerous tissues (NTs) using tissue microarray (TMA) technology. The
      functions of PAK5 were studied in vitro and in vivo. Cell Counting Kit-8 (CCK-8)
      and flow cytometry were performed to determine proliferation of breast cancer
      cells. Phosphorylation assay and co-immunoprecipitation (co-IP) were employed to
      identify the regulation mechanism of p65 by PAK5. The activation of Cyclin D1
      promoter was measured with luciferase reporter assay. Xenograft models in nude
      mice were established to explore the roles of PAK5 in breast cancer growth.
      RESULTS: In this study, we show that PAK5 is highly expressed in breast cancer
      tissues and the increased PAK5 is significantly associated with breast cancer
      progression. Overexpression of PAK5 promotes the proliferation and cell-cycle
      progression by increasing the expression of Cyclin D1 in vitro and in vivo.
      Mechanistic studies demonstrated that PAK5 can promote the phosphorylation and
      the nuclear translocation of p65 subunit of nuclear factor-kappaB (NF-kappaB).
      Furthermore, p65 can directly bind to the promoter of Cyclin D1 and mediate an
      increase in its protein expression. CONCLUSIONS: Taken together, our findings
      suggest that PAK5 may serve as a potential prognosis marker and therapeutic
      target for human breast cancer.

PMID- 29041984
TI  - Prevalence and multilocus genotyping of Giardia duodenalis in pigs of Shaanxi
      Province, northwestern China.
AB  - BACKGROUND: Giardiasis, caused by Giardia duodenalis (syn. Giardia intestinalis,
      Giardia lamblia), is a significant zoonotic parasitic disease of animals and
      humans worldwide. Accurate genotyping of G. duodenalis is essential for efficient
      control and management of giardiasis. The objectives of the present study were to
      investigate the prevalence and assemblages of giardiasis in pigs in Shaanxi
      Province, northwestern China, and for the first time study multilocus genotypes
      (MLGs) in pigs using multilocus genotyping technology in this region. RESULTS: Of
      560 faecal samples collected from five farms in Shaanxi Province, 45 were
      positive for G. duodenalis and significant differences in prevalence were
      observed among different locations. Differences in prevalence were also detected
      in pigs of different age groups, with the highest prevalence in sows and the
      lowest in boars. Two assemblages, A and E, were identified, and a mixed infection
      of both A and E was identified in one faecal sample. Assemblage E was predominant
      and widely distributed in all investigated areas and age groups. Genetic
      viability was detected for both assemblages, and four different multi-locus
      genotypes (MLGs) within assemblage E were found, MLGE1-MLGE4. CONCLUSIONS:
      Giardia duodenalis was detected in pigs from Shaanxi Province, northwestern
      China, and genetic diversity was observed in these infections. Both assemblages A
      and E were detected, and four distinct MLGs within assemblage E were identified.
      These findings provide new data for controlling G. duodenalis infection in pigs.

PMID- 29041985
TI  - Simplified prognostic model for critically ill patients in resource limited
      settings in South Asia.
AB  - BACKGROUND: Current critical care prognostic models are predominantly developed
      in high-income countries (HICs) and may not be feasible in intensive care units
      (ICUs) in lower- and middle-income countries (LMICs). Existing prognostic models
      cannot be applied without validation in LMICs as the different disease profiles,
      resource availability, and heterogeneity of the population may limit the
      transferability of such scores. A major shortcoming in using such models in LMICs
      is the unavailability of required measurements. This study proposes a simplified
      critical care prognostic model for use at the time of ICU admission. METHODS:
      This was a prospective study of 3855 patients admitted to 21 ICUs from
      Bangladesh, India, Nepal, and Sri Lanka who were aged 16 years and over and
      followed to ICU discharge. Variables captured included patient age, admission
      characteristics, clinical assessments, laboratory investigations, and treatment
      measures. Multivariate logistic regression was used to develop three models for
      ICU mortality prediction: model 1 with clinical, laboratory, and treatment
      variables; model 2 with clinical and laboratory variables; and model 3, a purely
      clinical model. Internal validation based on bootstrapping (1000 samples) was
      used to calculate discrimination (area under the receiver operating
      characteristic curve (AUC)) and calibration (Hosmer-Lemeshow C-Statistic; higher
      values indicate poorer calibration). Comparison was made with the Acute
      Physiology and Chronic Health Evaluation (APACHE) II and Simplified Acute
      Physiology Score (SAPS) II models. RESULTS: Model 1 recorded the respiratory
      rate, systolic blood pressure, Glasgow Coma Scale (GCS), blood urea, haemoglobin,
      mechanical ventilation, and vasopressor use on ICU admission. Model 2, named
      TropICS (Tropical Intensive Care Score), included emergency surgery, respiratory
      rate, systolic blood pressure, GCS, blood urea, and haemoglobin. Model 3 included
      respiratory rate, emergency surgery, and GCS. AUC was 0.818 (95% confidence
      interval (CI) 0.800-0.835) for model 1, 0.767 (0.741-0.792) for TropICS, and
      0.725 (0.688-0.762) for model 3. The Hosmer-Lemeshow C-Statistic p values were
      less than 0.05 for models 1 and 3 and 0.18 for TropICS. In comparison, when
      APACHE II and SAPS II were applied to the same dataset, AUC was 0.707 (0.688
      0.726) and 0.714 (0.695-0.732) and the C-Statistic was 124.84 (p < 0.001) and
      1692.14 (p < 0.001), respectively. CONCLUSION: This paper proposes TropICS as the
      first multinational critical care prognostic model developed in a non-HIC
      setting.

PMID- 29041986
TI  - Fluorescence optical imaging in pediatric patients with inflammatory and non
      inflammatory joint diseases: a comparative study with ultrasonography.
AB  - BACKGROUND: Valid detection of arthritis is essential in differential diagnosis
      of joint pain. Indocyanin green (ICG)-enhanced fluorescence optical imaging (FOI)
      is a new imaging method that visualizes inflammation in wrist and finger joints.
      Objectives of this study were to compare FOI with ultrasonography (US, by gray
      scale (GS) and power Doppler (PD)) and clinical examination (CE) and to estimate
      the predictive power of FOI for discrimination between inflammatory and non
      inflammatory juvenile joint diseases. METHODS: FOI and GSUS/PDUS were performed
      in both hands of 76 patients with joint pain (53 with juvenile idiopathic
      arthritis (JIA), 23 with non-inflammatory joint diseases). Inflammation was
      graded by a semiquantitative score (grades 0-3) for each imaging method. Joints
      were defined clinically active if swollen or tender with limited range of motion.
      Sensitivity and specificity of FOI in three phases dependent on ICG enhancement
      (P1-P3) were analyzed with CE and GSUS/PDUS as reference. RESULTS: For JIA
      patients, FOI had an overall sensitivity of 67.3%/72.0% and a specificity of
      65.0%/58.8% with GSUS/PDUS as reference; specificity was highest in P3 (GSUS
      94.3%/PDUS 91.7%). FOI was more sensitive for detecting clinically active joints
      than GSUS/PDUS (75.2% vs 57.3%/32.5%). In patients with non-inflammatory joint
      diseases both FOI and US showed positive (i.e., pathological) findings (25% and
      14% of joints). The predictive value for discrimination between inflammatory and
      non-inflammatory joint diseases was 0.79 for FOI and 0.80/0.85 for GSUS/PDUS.
      CONCLUSIONS: Dependent on the phase evaluated, FOI had moderate to good agreement
      with CE and US. Both imaging methods revealed limitations and should be
      interpreted cautiously. FOI may provide an additional diagnostic method in
      pediatric rheumatology. TRIAL REGISTRATION: Deutsches Register Klinischer Studien
      DRKS00012572 . Registered 31 July 2017.

PMID- 29041987
TI  - The effects of melatonin on colonization of neonate spermatogonial mouse stem
      cells in a three-dimensional soft agar culture system.
AB  - BACKGROUND: Melatonin is a pleiotropic hormone with powerful antioxidant activity
      both in vivo and in vitro. The present study aimed to investigate the effects of
      melatonin on the proliferation efficiency of neonatal mouse spermatogonial stem
      cells (SSCs) using a three-dimensional soft agar culture system (SACS) which has
      the capacity to induce development of SSCs similar to in vivo conditions.
      METHODS: SSCs were isolated from testes of neonate mice and their purities were
      assessed by flow cytometry using PLZF antibody. Isolated testicular cells were
      cultured in the upper layer of the SACS in alphaMEM medium in the absence or
      presence of melatonin extract for 4 weeks. RESULTS: The identity of colonies was
      confirmed by alkaline phosphatase staining and immunocytochemistry using PLZF and
      alpha6 integrin antibodies. The number and diameter of colonies of SSCs in the
      upper layer were evaluated at days 14 and 28 of culture. The number and diameter
      of colonies of SSCs were significantly higher in the melatonin group compared
      with the control group. The levels of expression of ID-4 and Plzf, unlike c-kit,
      were significantly higher in the melatonin group than in the control group.
      CONCLUSIONS: Results of the present study show that supplementation of the
      culture medium (SACS) with 100 MUM melatonin significantly decreased reactive
      oxygen species (ROS) production in the treated group compared with the control
      group, and increased SSC proliferation.

PMID- 29041988
TI  - Characterization of novel microneme adhesive repeats (MAR) in Eimeria tenella.
AB  - BACKGROUND: The phylum Apicomplexa comprises a wide variety of parasites of
      significant medical and economic relevance. These parasites have extremely
      different host and tissue tropisms; for example Toxoplasma gondii can invade
      virtually any nucleated cell and infect almost all warm-blooded vertebrates,
      whereas Eimeria tenella infects only chickens and is restricted in its growth to
      epithelial cells of the caecum. Proteins released from the microneme secretory
      organelles (MICs) are critical for apicomplexan invasion of host cells and allow
      parasites to bind a diverse range of host cell oligosaccharide epitopes. MICs
      bear modular arrangements of sequences with adhesive proteins and interestingly
      the sialic-acid binding MAR (microneme adhesive repeat) domain containing
      proteins (MCPs) are suggested to make significant contributions to the different
      host and tissue tropisms of T. gondii and E. tenella. RESULTS: In this study, we
      evaluated the binding capacity of Type I MAR domains from novel E. tenella MCPs.
      Variants of the previously described HxT motif were analysed showing that HxT and
      VxT variants bind, whereas HxS and YxE variants did not. One of these MCP
      containing a single MAR (EtMCP2) showed an apical localization when expressed as
      a fusion with the fluorescent reporter mCherry in transgenic populations and a
      similar pattern of transcripts per zoite during endogenous development in vitro
      as the well-characterised microneme protein EtMIC2. CONCLUSIONS: Variation in the
      binding properties of the MAR of different EtMCPs was confirmed and their ability
      to bind a wider range of sialic acids and terminal linkages should be studied. In
      addition, transgenesis technology has been used for first time in Eimeria
      parasites as a rapid tool for the study of endogenous protein localization by
      fusion with a fluorescent reporter.

PMID- 29041989
TI  - Links of gut microbiota composition with alcohol dependence syndrome and
      alcoholic liver disease.
AB  - BACKGROUND: Alcohol abuse has deleterious effects on human health by disrupting
      the functions of many organs and systems. Gut microbiota has been implicated in
      the pathogenesis of alcohol-related liver diseases, with its composition
      manifesting expressed dysbiosis in patients suffering from alcoholic dependence.
      Due to its inherent plasticity, gut microbiota is an important target for
      prevention and treatment of these diseases. Identification of the impact of
      alcohol abuse with associated psychiatric symptoms on the gut community structure
      is confounded by the liver dysfunction. In order to differentiate the effects of
      these two factors, we conducted a comparative "shotgun" metagenomic survey of 99
      patients with the alcohol dependence syndrome represented by two cohorts-with and
      without liver cirrhosis. The taxonomic and functional composition of the gut
      microbiota was subjected to a multifactor analysis including comparison with the
      external control group. RESULTS: Alcoholic dependence and liver cirrhosis were
      associated with profound shifts in gut community structures and metabolic
      potential across the patients. The specific effects on species-level community
      composition were remarkably different between cohorts with and without liver
      cirrhosis. In both cases, the commensal microbiota was found to be depleted.
      Alcoholic dependence was inversely associated with the levels of butyrate
      producing species from the Clostridiales order, while the cirrhosis-with multiple
      members of the Bacteroidales order. The opportunist pathogens linked to alcoholic
      dependence included pro-inflammatory Enterobacteriaceae, while the hallmarks of
      cirrhosis included an increase of oral microbes in the gut and more frequent
      occurrence of abnormal community structures. Interestingly, each of the two
      factors was associated with the expressed enrichment in many Bifidobacterium and
      Lactobacillus-but the exact set of the species was different between alcoholic
      dependence and liver cirrhosis. At the level of functional potential, the
      patients showed different patterns of increase in functions related to alcohol
      metabolism and virulence factors, as well as pathways related to inflammation.
      CONCLUSIONS: Multiple shifts in the community structure and metabolic potential
      suggest strong negative influence of alcohol dependence and associated liver
      dysfunction on gut microbiota. The identified differences in patterns of impact
      between these two factors are important for planning of personalized treatment
      and prevention of these pathologies via microbiota modulation. Particularly, the
      expansion of Bifidobacterium and Lactobacillus suggests that probiotic
      interventions for patients with alcohol-related disorders using representatives
      of the same taxa should be considered with caution. Taxonomic and functional
      analysis shows an increased propensity of the gut microbiota to synthesis of the
      toxic acetaldehyde, suggesting higher risk of colorectal cancer and other
      pathologies in alcoholics.

PMID- 29041992
TI  - Understanding Patterns of Socioeconomic and Demographic Factors Along With Health
      Services Provider Availability for Zika Outbreak in South Florida.
AB  - In this study, we analyzed the patterns of socioeconomic and demographic factors
      along with health services provider availability for the current Zika outbreak in
      Miami-Dade County, South Florida. We used Center for Consumer Information &
      Insurance Oversight (CCIIO) Machine-Readable Public Use Files (MR-PUFs) to
      examine provider availability in combination with socioeconomic and demographic
      factors that could potentially lead to healthcare disparities between any
      underserved population of the Wynwood neighborhood and the broader population of
      Miami-Dade County. MR-PUFs contain public provider-level data from states that
      are participating in the Federally Facilitated Marketplace. According to CCIIO,
      an issuer of a Qualified Health Plan that uses a provider network must maintain a
      network that is sufficient in the number and types of providers, including
      providers that specialize in mental-health and substance-use disorder services,
      to assure that all services will be accessible to enrollees without unreasonable
      delay. (Disaster Med Public Health Preparedness. 2018;12:455-459).

PMID- 29041991
TI  - Neutrophil lymphocyte ratio and duration of prior anti-angiogenic therapy as
      biomarkers in metastatic RCC receiving immune checkpoint inhibitor therapy.
AB  - BACKGROUND: There is an unmet need to determine factors predictive of clinical
      benefit, to guide therapeutic sequencing and selection in metastatic RCC (mRCC).
      We evaluated clinical factors such as the neutrophil lymphocyte ratio (NLR) and
      duration of prior anti-vascular endothelial growth factor (VEGF) inhibitors, as
      predictors of response rate, progression free survival (PFS) and overall survival
      (OS) in mRCC patients treated with immune checkpoint inhibitor (ICI). METHODS:
      Regulatory approval was obtained. A single center retrospective chart review of
      mRCC patients at Karmanos Cancer Institute, treated with ICI based therapy (PD
      1/PD-L1 inhibitors) was conducted. Data were collected on demographics, smoking
      status, prognostic scoring (Memorial Sloan Kettering and Heng criteria), NLR
      pretherapy, post 1 and 4 doses of ICI, and duration of prior anti-VEGF therapy
      >=6 months or <6. RESULTS: 42 patients were evaluated with median age of 61 years
      (range, 24-85). Pretherapy NLR < 3 and >=3 was seen in 19 (45%) and 23 (55%)
      patients, respectively. 24 (57%) and 18 (43%) patients had prior anti-VEGF
      inhibitors for a duration of >=6 months and <6 months, respectively. 12 (29%), 22
      (52%) and 8 (19%) patients had favorable, intermediate and poor risk disease
      based on Heng criteria, respectively. Multivariable analysis showed pretherapy
      NLR >=3 was predictive of shorter PFS and OS when treated with ICI with median
      3.08 months and 13.50 months, respectively, versus 15.57 months and not reached
      for NLR < 3 (adjusted p-values =0.003 and 0.025, respectively). Prior anti-VEGF
      therapy <6 months was predictive of increased likelihood of benefit from ICI
      therapies (adjusted p = 0.028). The median PFS was 3.72 months and 14.33 months,
      respectively, in cases with prior anti-VEGF therapy for >=6 months and <6 months.
      CONCLUSION: Pretherapy NLR <3 and duration of prior anti-VEGF therapy of <6
      months, are independent statistically significant predictors of longer PFS and OS
      with ICI therapy in mRCC. Validation is required in a larger sample size with
      multi-institutional collaboration.

PMID- 29041993
TI  - Development of a Contextualized Version of the Multiple Errands Test for People
      with Substance Dependence.
AB  - BACKGROUND: Substance dependence is associated with deficits in several areas of
      executive functioning, such as planning and multitasking. Traditional tests of
      executive functioning have been criticized for their low ecological validity.
      Shallice and Burgess (1991) developed the Multiple Errands Test (MET), where
      participants are required to perform multiple tasks in a real-world setting. In
      this study, we aimed to adapt the MET for use in populations with substance
      dependence. OBJECTIVES: This study aimed to: (1) examine the applicability of a
      contextualized version of the Multiple Errands Test, namely, the Multiple Errands
      Test - Contextualized Version (MET-CV); (2) study the testing context reliability
      and convergent validity of MET-CV scores; (3) compare the performance of people
      with substance dependence to a control group. METHODS: Data were collected from
      60 participants with substance dependence and 30 healthy controls. Both groups
      performed a neuropsychological assessment, which consisted of the MET-CV and
      traditional neuropsychological tests (Letter Number Sequencing, Zoo Map Test,
      Revised Strategy Application Test, Information Sampling Test, Stockings of
      Cambridge). RESULTS: The MET-CV has adequate testing context reliability and
      moderate convergent validity relative to traditional planning measures. People
      with substance dependence (PWSD) showed significant deficits in executive
      function tests compared to healthy controls, most notably on the MET-CV rather
      than on traditional neuropsychological tests. CONCLUSIONS: The MET-CV can be
      feasibly applied in the context of therapeutic communities treatment in PWSD. The
      MET-CV showed adequate reliability and validity, and detected planning deficits
      in PWSD. (JINS, 2018, 24, 347-359).

PMID- 29041990
TI  - Piceatannol induced apoptosis through up-regulation of microRNA-181a in melanoma
      cells.
AB  - BACKGROUND: Melanoma took top position among the lethal cancers and, despite
      there have been some great attempts made to increase the natural life of patients
      with metastatic disease, long-lasting and complete remissions are few.
      Piceatannol, owns the similar function as resveratrol, has been defined as an
      anti-cancer agent playing important role in inhibition of proliferation,
      migration and metastasis in various cancer. Thus, we aim to investigate the anti
      cancer effect and mechanisms of piceatannol in melanoma cells. METHODS: Melanoma
      cell lines WM266-4 and A2058 were treated either with or without piceatannol.
      Cell viability and cell apoptosis were assessed by using MTT and Annexin V/PI
      assay, respectively. Cells were transfected with specific miRNA using
      Lipfectamine 2000. miRNA bingding ability to 3'-UTR region within specific gene
      was assed by firefly luciferase analysis. Gene and protein expression was
      eveluated by qRT-PCR and western blot analysis, respectively. RESULTS: Our study
      showed that piceatannol inhibited WM266-4 and A2058 cells growth and induced
      apoptosis. Totally, 16 differentially expressed miRNAs were screened out
      including 8 up-regulated and 8 down-regulated miRNAs. Expression level of miR
      181a is significantly higher in piceatannol-treated cells than normal control and
      is lower in melanoma cancer tissues than its adjacent normal tissues. Bcl-2 is a
      target gene of miR-181a. Moreover, silencing of miR-181a reverses the decrease of
      cell viability induced by piceatannol in WM266-4 and A2058 cells. Taken together,
      present study uncovered the ability of piceatannol to repress melanoma cell
      growth and clarified the contribution of miR-181a in the anticancer role of
      piceatannol. CONCLUSION: The present study proposes that piceatannol can be taken
      into account to be a hopeful anticancer agent for melanoma.

PMID- 29041994
TI  - Hospital Surge Capacity: A Web-Based Simulation Tool for Emergency Planners.
AB  - The National Center for the Study of Preparedness and Catastrophic Event Response
      (PACER) has created a publicly available simulation tool called Surge (accessible
      at http://www.pacerapps.org) to estimate surge capacity for user-defined
      hospitals. Based on user input, a Monte Carlo simulation algorithm forecasts
      available hospital bed capacity over a 7-day period and iteratively assesses the
      ability to accommodate disaster patients. Currently, the tool can simulate bed
      capacity for acute mass casualty events (such as explosions) only and does not
      specifically simulate staff and supply inventory. Strategies to expand hospital
      capacity, such as (1) opening unlicensed beds, (2) canceling elective admissions,
      and (3) implementing reverse triage, can be interactively evaluated. In the
      present application of the tool, various response strategies were systematically
      investigated for 3 nationally representative hospital settings (large urban,
      midsize community, small rural). The simulation experiments estimated baseline
      surge capacity between 7% (large hospitals) and 22% (small hospitals) of staffed
      beds. Combining all response strategies simulated surge capacity between 30% and
      40% of staffed beds. Response strategies were more impactful in the large urban
      hospital simulation owing to higher baseline occupancy and greater proportion of
      elective admissions. The publicly available Surge tool enables proactive
      assessment of hospital surge capacity to support improved decision-making for
      disaster response. (Disaster Med Public Health Preparedness. 2018;12:513-522).

PMID- 29041995
TI  - Reproducibility of Cognitive Profiles in Psychosis Using Cluster Analysis.
AB  - OBJECTIVES: Cognitive dysfunction is a core symptom dimension that cuts across
      the psychoses. Recent findings support classification of patients along the
      cognitive dimension using cluster analysis; however, data-derived groupings may
      be highly determined by sampling characteristics and the measures used to derive
      the clusters, and so their interpretability must be established. We examined
      cognitive clusters in a cross-diagnostic sample of patients with psychosis and
      associations with clinical and functional outcomes. We then compared our findings
      to a previous report of cognitive clusters in a separate sample using a different
      cognitive battery. METHODS: Participants with affective or non-affective
      psychosis (n=120) and healthy controls (n=31) were administered the MATRICS
      Consensus Cognitive Battery, and clinical and community functioning assessments.
      Cluster analyses were performed on cognitive variables, and clusters were
      compared on demographic, cognitive, and clinical measures. Results were compared
      to findings from our previous report. RESULTS: A four-cluster solution provided a
      good fit to the data; profiles included a neuropsychologically normal cluster, a
      globally impaired cluster, and two clusters of mixed profiles. Cognitive burden
      was associated with symptom severity and poorer community functioning. The
      patterns of cognitive performance by cluster were highly consistent with our
      previous findings. CONCLUSIONS: We found evidence of four cognitive subgroups of
      patients with psychosis, with cognitive profiles that map closely to those
      produced in our previous work. Clusters were associated with clinical and
      community variables and a measure of premorbid functioning, suggesting that they
      reflect meaningful groupings: replicable, and related to clinical presentation
      and functional outcomes. (JINS, 2018, 24, 382-390).

PMID- 29041996
TI  - Preparedness Training Programs for Working With Deaf and Hard of Hearing
      Communities and Older Adults: Lessons Learned From Key Informants and Literature
      Assessments.
AB  - OBJECTIVES: The objectives of this study were to (1) identify available training
      programs for emergency response personnel and public health professionals on
      addressing the needs of Deaf and hard of hearing individuals and older adults,
      (2) identify strategies to improve these training programs, and (3) identify gaps
      in available training programs and make recommendations for addressing these
      gaps. METHODS: A literature review was conducted to identify relevant training
      programs and identify lessons learned. Interviews were conducted by telephone or
      email with key informants who were subject matter experts who worked with Deaf
      and hard of hearing persons (n=11) and older adults (n=11). RESULTS: From the
      literature, 11 training programs targeting public health professionals and
      emergency response personnel serving Deaf and hard of hearing individuals (n=7)
      and older adults (n=4) were identified. The 4 training programs focused on older
      adults had corresponding evaluations published in the literature. Three (43%) of
      the 7 training programs focused on Deaf and hard of hearing persons included
      individuals from the affected communities in the development and implementation
      of the training. Key informant interviews identified common recommendations for
      improving training programs: (1) training should involve collaboration across
      different emergency, state, federal, and advocacy agencies; (2) training should
      involve members of affected communities; (3) training should be more widely
      accessible and affordable; and (4) training should teach response personnel
      varied communication techniques relevant to the Deaf and hard of hearing and
      older adult communities. CONCLUSIONS: Developing effective, accessible, and
      affordable training programs for emergency response personnel working with Deaf
      and hard of hearing persons, some of whom belong to the older adult population,
      will require a collaborative effort among emergency response agencies, public
      health organizations, and members of the affected communities. (Disaster Med
      Public Health Preparedness. 2018;12:606-614).

PMID- 29041997
TI  - A Web-based module and online video for pain management education for caregivers
      of children with fractures: A randomized controlled trial.
AB  - : IntroductionOver 80% of children experience compromise in functioning following
      a fracture. Digital media may improve caregiver knowledge of managing fracture
      pain at home. OBJECTIVES: To determine whether an educational video was superior
      to an interactive web-based module (WBM) and verbal instructions, the standard of
      care (SOC). METHODS: This randomized trial included caregivers of children 0-17
      years presenting to the emergency department (ED) with non-operative fractures.
      Primary outcome was the gain score (pre-post intervention) on a 21-item
      questionnaire testing knowledge surrounding pain recognition and management for
      children with fractures. Secondary outcomes included survey of caregiver
      confidence in managing pain (five-item Likert scale), number of days with
      difficulty sleeping, before return to a normal diet, and work/school missed.
      RESULTS: We analyzed 311 participants (WBM 99; video 108; SOC 104) with a mean
      (SD) child age of 9.6 (4.2) years, of which 125/311 (40.2%) were female. The
      video (delta=2.3, 95% CI: 1.3, 3.3; p<0.001) and WBM (delta=1.6; 95% CI: 0.5,
      2.6; p=0.002) groups had significantly greater gain scores than the SOC group.
      The mean video gain score was not significantly greater than WBM (delta=0.7; 95%
      CI: -0.3, 1.8; p=0.25). There were no significant differences in caregiver
      confidence (p=0.4), number of absent school days (p=0.43), nights with difficulty
      sleeping (p=0.94), days before return to a normal diet (p=0.07), or workdays
      missed (p=0.95). CONCLUSIONS: A web-based module and online video are superior to
      verbal instructions for improving caregiver knowledge on management of children's
      fracture pain without improvement in functional outcomes.

PMID- 29041998
TI  - Rethinking dementias.

PMID- 29041999
TI  - Electrodiagnostic and nerve ultrasonographic features in upper limb spasticity:
      an observational study.
AB  - To better understand the effects of spasticity on peripheral nerves, we evaluated
      the electrodiagnostic and nerve ultrasonographic features of the median and ulnar
      nerves in adults with upper limb spasticity. Twenty chronic stroke patients with
      spastic hemiparesis underwent nerve conduction study and nerve ultrasonography of
      the median and ulnar nerves at both upper limbs. Affected versus unaffected upper
      limb comparisons showed significant differences in the median and ulnar nerve
      distal motor latencies, compound muscle action potentials and F-wave minimal
      latencies. Furthermore, we observed a significantly greater median nerve
      crosssectional area at the elbow of the affected upper limb compared with the
      unaffected one. Our findings confirmed electrodiagnostic asymmetries and nerve
      ultrasonographic abnormalities in the affected versus the unaffected upper limb
      after stroke. Slight changes in lower motor neuron activity and spasticity might
      contribute to these alterations.

PMID- 29042000
TI  - Nociceptive blink reflex habituation biofeedback in migraine.
AB  - Reduced habituation of the nociceptive blink reflex (NBR) is considered a trait
      marker for genetic predisposition to migraine. In this open-label randomized
      controlled study, we aimed to test the efficacy of a biofeedback training based
      on learning of habituation of the NBR (NBR biofeedback) compared with
      pharmacological (topiramate) treatment and NBR biofeedback plus topiramate
      treatment in a cohort of migraine without aura patients eligible for prophylaxis.
      Thirty-three migraine patients were randomly assigned to three months of
      treatment with: 1) NBR biofeedback, 2) NBR biofeedback plus topiramate 50 mg
      (b.i.d.), or 3) topiramate 50 mg (b.i.d.). Frequency of headache and disability
      changes were the main study outcomes. Anxiety, depression, sleep, fatigue,
      quality of life, allodynia and pericranial tenderness were also evaluated. NBR
      biofeedback reduced the R2 area, without improving R2 habituation. However, it
      reduced the frequency of headache and disability, similarly to the combined
      treatment and topiramate alone. Reduced habituation of the NBR is a stable
      neurophysiological pattern, scarcely modifiable by learning procedures. Training
      methods able to act on stress-related responses may modulate cortical mechanisms
      inducing migraine onset and trigeminal activation under stressful trigger
      factors.

PMID- 29042001
TI  - Recovery from vegetative state of patients with a severe brain injury: a 4-year
      real-practice prospective cohort study.
AB  - Patients who have suffered severe traumatic or nontraumatic brain injuries can
      show a progressive recovery, transitioning through a range of clinical
      conditions. They may progress from coma to a vegetative state (VS) and/or a
      minimally conscious state (MCS). A longer duration of the VS is known to be
      related to a lower probability of emergence from it; furthermore, the literature
      seems to lack evidence of late improvements in these patients. This real-practice
      prospective cohort study was conducted in inpatients in a VS following a severe
      brain injury, consecutively admitted to a vegetative state unit (VSU). The aim of
      the study was to assess their recovery in order to identify variables that might
      increase the probability of a VS patient transitioning to MCS. Rehabilitation
      treatment included passive joint mobilisation and helping/placing patients into
      an upright sitting position on a tilt table. All the patients underwent a
      specific assessment protocol every month to identify any emergence, however late,
      from the VS. Over a 4-year period, 194 patients suffering sequelae of a severe
      brain injury, consecutively seen, had an initial Glasgow Coma Scale score <= 8.
      Of these, 63 (32.5%) were in a VS, 84 (43.3%) in a MCS, and 47 (24.2%) in a coma;
      of the 63 patients admitted in a VS, 49 (57.1% males and 42.9% females, mean age
      25.34 +/- 19.12 years) were transferred to a specialist VSU and put on a slow-to
      recover brain injury programme. Ten of these 49 patients were still in a VS after
      36 months; of these 10, 3 recovered consciousness, transitioning to a MCS, 2
      died, and 5 remained in a VS during the last 12 months of the observation.
      Univariate analysis identified male sex, youth, a shorter time from onset of the
      VS, diffuse brain injury, and the presence of status epilepticus as variables
      increasing the likelihood of transition to a MCS. Long-term monitoring of
      patients with chronic disorders of consciousness should be adequately implemented
      in order to optimise their access to rehabilitation services.

PMID- 29042002
TI  - Obstructive sleep apnea syndrome in Parkinson's disease and other parkinsonisms.
AB  - An association of obstructive sleep apnea syndrome (OSAS) and other sleep
      disordered breathing (SDB) with Parkinson's disease (PD) has been reported in
      some small studies. In the present study we investigated the occurrence of SDB in
      a large consecutive outpatient series. This is a case-control study in subjects
      attending a neurological clinic where all patients were screened for SDB by means
      of sleep-wake history, Epworth Sleepiness Scale, and full-night polysomnography,
      when indicated. 3194 patients were recruited. Of these, 194 were affected by PD
      and 77 by other parkinsonisms. Snoring, excessive daytime sleepiness and OSAS
      were more common in patients with PD or parkinsonisms (40.59, 5.9, and 4.06%)
      than in controls (35.58, 2.19, and 2.09%). Our study suggests an increased
      frequency of OSAS and other SDB in PD and parkinsonisms. Early detection and
      management of these disorders may have a substantial impact on quality of life
      and survival in these patients.

PMID- 29042003
TI  - Pisa syndrome in Parkinson's disease: electromyographic quantification of
      paraspinal and non-paraspinal muscle activity.
AB  - Patients with Parkinson's disease (PD) and Pisa syndrome (PS) may present tonic
      dystonic or compensatory (i.e. acting against gravity) hyperactivity in the
      paraspinal and non-paraspinal muscles. Electromyographic (EMG) activity was
      measured in nine patients with PD and PS, three with PD without PS, and five
      healthy controls. Fine-wire intramuscular electrodes were inserted bilaterally
      into the iliocostalis lumborum (ICL), iliocostalis thoracis (ICT), gluteus medius
      (GM), and external oblique (EO) muscles. The root mean square (RMS) of the EMG
      signal was calculated and normalized for each muscle. In stance condition, side
      to-side muscle activity comparisons showed a higher RMS only for the
      contralateral ICL in PD patients with PS (p=0.028). Moreover, with increasing
      degrees of lateral flexion, the activity of the EO and the ICL muscles
      progressively increased and decreased, respectively. The present data suggest
      that contralateral paraspinal muscle activity plays a crucial compensatory role
      and can be dysfunctional in PD patients with PS.

PMID- 29042004
TI  - Quantitative, functional MRI and neurophysiological markers in a case of
      Gerstmann-Straussler-Scheinker syndrome.
AB  - Gerstmann-Straussler-Scheinker syndrome (GSS) is an inherited autosomal dominant
      prion disease, caused by a codon 102 proline to leucine substitution (P102L) in
      the prion protein gene (PRNP). We describe the case of a 40-year-old male,
      affected by a slowly progressive gait disturbance, leg weakness and cognitive
      impairment. Genomic DNA revealed a point mutation of PRNP at codon 102, resulting
      in P102L, and the diagnosis of GSS was confirmed. Somatosensory evoked potentials
      showed alterations of principal parameters, particularly in the right upper and
      lower limbs. Laser-evoked potentials were indicative of nociceptive system
      impairment, especially in the right upper and lower limbs. Conventional magnetic
      resonance imaging (MRI) revealed marked atrophy of the vermis and cerebellar
      hemispheres and mild atrophy of the middle cerebellar peduncles and brainstem, as
      confirmed by a brain volume automatic analysis. Resting-state functional MRI
      showed increased functional connectivity in the bilateral visual cortex, and
      decreased functional connectivity in the bilateral frontal pole and supramarginal
      and precentral gyrus. Albeit limited to a single case, this is the first study to
      assess structural and functional connectivity in GSS using a multimodal approach.

PMID- 29042005
TI  - Analysis of Italian regulations on pathways of care for patients in a vegetative
      or minimally conscious state.
AB  - Different rehabilitation models for persons diagnosed with disorders of
      consciousness have been proposed in Europe during the last decade. In Italy, the
      Ministry of Health has defined a national healthcare model, although, to date,
      there is a lack of information on how this has been implemented at regional
      level. The INCARICO project collected information on different regional
      regulations, analysing ethical aspects and mapping care facilities (numbers of
      beds and medical units) in eleven regional territories. The researchers found a
      total of 106 laws; differences emerged both between regions and versus the
      national model, showing that patients with the same diagnosis may follow
      different pathways of care. An ongoing cultural shift from a treatment-oriented
      medical approach towards a care-oriented integrated biopsychosocial approach was
      found in all the welfare and healthcare systems analysed. Future studies are
      needed to explore the relationship between healthcare systems and the quality of
      services provided.

PMID- 29042006
TI  - Comparative study of cephalometric measurements using 3 imaging modalities.
AB  - BACKGROUND: The authors conducted a study to compare 2-dimensional (2D) lateral
      cephalometric radiography (LCR), 2D cone-beam computer tomographic (CBCT)
      generated cephalogram and 3-dimensional (3D) CBCT for assessing cephalometric
      measurements. METHODS: The authors took 2D LCR, 2D CBCT-generated cephalogram,
      and 3D CBCT images involving 60 participants. They obtained 11 angular and 11
      linear measurements for all images. They used 1-way analysis of variance and the
      Fisher least significant difference test for statistical comparisons. The authors
      used Pearson correlation and Pearson chi2 test to assess the relationship of
      these imaging modalities for vertical cephalometric analyses. RESULTS:
      Significant differences existed between the 2D cephalograms (LCR and CBCT
      generated cephalogram) and the 3D CBCT in 2 angular measurements (maxillary first
      incisor-nasion (N) point A [A] and mandibular first incisor-N point B (B) (P =
      .027 and P < .001, respectively) and 5 linear measurements (N menton[Me]/sella
      gonion [Go], condylion [Co]A, Co gnathion, Go-Me and anterior nasal spine
      posterior nasal spine) (P < .004). These measurement values with significant
      differences were generally greater (approximately 5 degrees  for angular
      measurements and 10 millimeters for linear measurements) on the 3D CBCT scans
      than on the 2D cephalograms. No significant difference was found between the 2 2D
      cephalograms (P > .164). No significant difference was found among the 3 imaging
      modalities for the vertical cephalometric analyses (P > .466). CONCLUSIONS:
      Significant differences existed between the 2D cephalograms (LCR and CBCT
      generated cephalogram) and the 3D CBCT scans in 2 angular and 5 linear
      measurements. The 2 2D cephalograms were similar for cephalometric measurements.
      The 3 imaging modalities had no significant difference for the vertical
      cephalometric analyses. CBCT might not add value for every orthodontic situation.
      PRACTICAL IMPLICATIONS: These results find the values of cephalometric
      measurements on 3D CBCT scans may be greater than on the conventional LCR for
      some parameters. The 2D CBCT-generated cephalogram could be an alternative to the
      conventional LCR for patients whose large-field-of-view CBCT images are already
      available.

PMID- 29042007
TI  - Direct Comparison of the Edwards Intuity Elite and Sorin Perceval S Rapid
      Deployment Aortic Valves.
AB  - BACKGROUND: Rapid deployment aortic valve replacement (RDAVR) has emerged as an
      attractive alternative to conventional aortic valve replacement. This single
      center study directly compared two commercially available rapid deployment valves
      with regard to clinical outcomes, valve-related complications, and hemodynamic
      performance. METHODS: A total of consecutive 156 patients underwent RDAVR with
      the Intuity Elite (Edwards Lifesciences, Irvine, CA [Intuity group, n = 117] or
      the Perceval S (Sorin Group Italia Srl, Saluggia, Italy [Perceval group, n = 39])
      between September 2012 and March 2016 at our institution. Perioperative data,
      including 30-day all-cause mortality, and echocardiographic measurements were
      assessed and retrospectively analyzed from our institutional database. RESULTS:
      Preoperative variables, including mean age (77 +/- 5 years), European System for
      Cardiac Operative Risk Evaluation (6.8 +/- 2.1), and body mass index (27 +/- 5
      kg/m2), did not differ between groups. More male patients (60% versus 15%) with a
      higher body surface area (1.9 +/- 0.2 m2 versus 1.7 +/- 0.2 m2) and body weight
      (78 +/- 13 kg versus 71 +/- 15 kg) were in the Intuity group compared with the
      Perceval group, respectively (p < 0.05). Implanted RDAVR size (23.3 +/- 1.8 mm
      versus 23.4 +/- 1.5 mm), concomitant coronary artery bypass graft surgery (48%
      versus 33%), number of grafts, cardiopulmonary bypass, and aortic clamp time were
      comparable between the Intuity group and the Perceval group. Thirty-day mortality
      (Intuity 2.6% versus Perceval 5.1%) and valve-related complications (Intuity
      12.0% versus Perceval 20.5%), including postoperative pacemaker implantation
      (Intuity 8.5% versus Perceval 12.8%), did not differ between groups. At discharge
      echocardiography, indexed effective orifice area was higher in the Intuity group,
      but peak or mean pressure gradients were comparable between groups. CONCLUSIONS:
      Performing RDAVR with the Intuity and Perceval rapid deployment valves provides
      comparable good clinical outcomes and valve hemodynamics, with low valve-related
      complication rates. The rate of pacemaker implantation was comparable for both
      rapid deployment valves, ranging from 8% to 13%.

PMID- 29042008
TI  - Discussion of: "Risky business? Investigating outcomes of patients undergoing
      urgent laparoscopic appendectomy on antithrombotic therapy".

PMID- 29042009
TI  - Identification of new CpG oligodeoxynucleotide motifs that induce expression of
      interleukin-1beta and nitric oxide in avian macrophages.
AB  - Unmethylated CpG motifs are known to stimulate mammalian toll-like receptor-9
      expressing cells such as macrophages. However, the magnitude of immune
      stimulation by CpG-motif can be sequence- and host-specific, implying the
      importance of identifying new immune-stimulatory motifs. This study aimed to
      determine the frequency distribution of 256 unique hexamers CpG-motifs in the
      Salmonella genome and to characterize their immune-stimulatory activity in avian
      host. We synthesized 256 CpG oligodeoxynucleotides (CpG-ODNs) each containing
      triplicates of a unique hexamer CpG-motif and tested their ability to induce
      expression of pro-inflammatory cytokine IL-1beta in avian macrophages using q-RT
      PCR in four rounds of screening assays. CpG-ODNs that induced significantly
      higher IL-1beta expression were also subjected to Griess assay to determine their
      ability to induce nitric oxide (NO) production in avian macrophages. This
      analysis resulted in identification of 7 CpG-ODNs that consistently induced IL
      1beta expression and NO production in avian macrophages at a level similar to the
      expression achieved using commercially available PTO-CpG-ODN 2007 and LPS derived
      from Salmonella. To the best of our knowledge, this is the first report showing
      comprehensive screening of all possible unique CpG hexamer (n=256) motifs for
      their ability to induce IL-1beta expression and NO production in avian
      macrophages. We also show that the newly identified CpG-motifs with high immune
      stimulatory activity are widely distributed in Salmonella genome. The CpG-ODNs
      identified in this study may serve as promising immunoprophylactics to potentiate
      innate responses in chickens against Salmonella and other infectious agents.

PMID- 29042010
TI  - Purification of chicken IgY by binding capture using elastin-like polypeptide
      tagged immunoglobulin-binding domain of streptococcal protein G.
AB  - Chicken egg yolk immunoglobulin (IgY) is a superior alternative to mammalian
      immunoglobulin, but its practical application is limited due to the complex
      purification procedure. In this study, the C2 domain of streptococcal protein G
      (SPG) with the binding affinity for chicken IgY was expressed in E. coli as an
      elastin-like polypeptide (ELP) fusion protein, and purified to a high purity by
      inverse transition cycling (ITC). Binding experiments showed that chicken IgY
      could bind to and eluted off the ELP-C2 fusion protein in pH-, temperature-
      and/or time-dependent manners. By using the ELP-C2 protein, a simple chicken IgY
      purification method was developed, and its purification performance was compared
      with that of ammonium sulfate precipitation and ethanol fractionation.
      Quantitative SDS-PAGE analysis showed that the ELP-C2 binding capture method
      provided a chicken IgY purity of 96.3% and a recovery of 64%, both of which were
      significantly higher than that of the two traditional methods The ELP-C2 binding
      capture method could be accomplished within 3h, in contrast to 30.3h for ammonium
      sulfate precipitation or 4.3h for ethanol fractionation. These data suggest that
      the ELP-C2 binding capture was a simple, efficient and cost-effective method for
      purification of chicken IgY.

PMID- 29042012
TI  - Molecular cloning and functional characterization of peptidoglycan recognition
      protein OmPGRP-L2 from the rainbow trout, Oncorhynchus mykiss.
AB  - Peptidoglycan recognition proteins (PGRPs), a group of pattern recognition
      receptors (PRRs), are innate immune molecules that are structurally conserved
      through evolution in both invertebrate and vertebrate animals. In teleost fish,
      several PGRPs have been characterized recently. They have both amidase activity
      and bactericidal activity and are involved in indirectly killing bacteria and
      regulating multiple signaling pathways. However, the knowledge of functional
      similarity and divergence between PGRP paralogs for their role as an immune
      modulator in teleost fish is still limited. In this study, we identified a novel
      PGRP paralog, termed OmPGRP-L2 from the rainbow trout (Oncorhynchus mykiss).
      OmPGRP-L2 contains the conserved PGRP domain and the four Zn2+-binding amino acid
      residues required for amidase activity. Quantitative RT-PCR analysis indicated
      that OmPGRP-L2 is highly expressed in liver. Overexpression of OmPGRP-L2 in a
      rainbow trout hepatocyte cell line RTH-149 challenged with Edwardsiella tarda
      resulted in down-regulation of IL-1beta and TNF-alpha expression. When
      overexpressed in RTH-149 cells, OmPGRP-L2 inhibited NF-kappaB activity with or
      without bacterial stimulation. Collectively, these findings suggest that OmPGRP
      L2 has an immunomodulatory function, via NF-kappaB inhibition in liver.

PMID- 29042011
TI  - Differences in innate and adaptive immune response traits of Pahari (Indian non
      descript indigenous breed) and Jersey crossbred cattle.
AB  - Cattle are an integral part of the largely agrarian economy of India. Indigenous
      breeds of cattle comprise about 80% of total cattle population of the country and
      contribute significantly to the overall milk production. There are 40 recognized
      indigenous breeds of cattle and a number of uncharacterized non-descript cattle.
      Pahari cattle of Himachal Pradesh in Northern India are one such non-descript
      indigenous breed. Here we describe a comprehensive evaluation of
      haematobiochemical parameters and innate and adaptive immune response traits of
      Pahari cattle and a comparison with Jersey crossbred cattle. The study shows
      demonstrable differences in the two breeds with respect to some innate and
      adaptive immunological traits. This is a first attempt to characterize immune
      response traits of Pahari cattle and the results of the study provide an
      understanding of breed differences in immune status of cattle which could be
      useful for their breeding and conservations programs.

PMID- 29042014
TI  - Effects of cathelicidin-derived peptide from reptiles on lipopolysaccharide
      induced intestinal inflammation in weaned piglets.
AB  - Cathelicidins are the largest family of antimicrobial peptides. C-BF, which is
      short for Cathelicidin-Bungarus Fasciatus, was isolated from snake venom. C-BF
      was found to be the most potential substitutes for antibiotics. In this study, we
      analyzed the effects of cathelicidin-derived peptide C-BF, on lipopolysaccharide
      (LPS)-induced intestinal damage in weaned piglets, to evaluate the therapeutic
      effect of C-BF on infectious disease of piglets. Twenty-four piglets were
      randomly assigned into four groups: control, C-BF, LPS, and C-BF+LPS. The LPS and
      C-BF+LPS groups were intraperitoneally injected with LPS at fixed timepoints,
      while the control and C-BF groups were injected with equal volumes of saline. The
      C-BF and C-BF+LPS groups were then intraperitoneally injected with antimicrobial
      peptide C-BF, while the control and LPS groups were injected with equal volumes
      of saline. All piglets were observed for 15days and then sacrificed for analysis.
      The results showed that C-BF significantly improved the growth performance of
      weaned piglets compared with LPS-treated animals (P<0.05), and that C-BF could
      ameliorate the structural and developmental damage to the small intestine caused
      by LPS treatment. Further, the level of apoptosis in the LPS group was
      significantly higher than in the other three groups (P<0.05), as was the invasion
      of inflammatory cells into the intestinal mucosa of the jejunum (P<0.05), leading
      to increased secretion of pro-inflammatory cytokines. In conclusion, the study
      indicates that C-BF treatment may be a potential therapy for LPS/pathogen-induced
      intestinal injury in piglets.

PMID- 29042013
TI  - Inhibition of microsomal prostaglandin E-synthase-1 (mPGES-1) selectively
      suppresses PGE2 in an in vitro equine inflammation model.
AB  - Inhibition of prostaglandin E2 (PGE2) production effectively limits inflammation
      in horses, however nonspecific prostaglandin blockade via cyclooxygenase (COX)
      inhibition elicits deleterious gastrointestinal side effects in equine patients.
      Thus, more selective PGE2 targeting therapeutics are needed to treat inflammatory
      disease in horses. One potential target is microsomal prostaglandin E-synthase-1
      (mPGES-1), which is the terminal enzyme downstream of COX-2 in the inducible PGE2
      synthesis cascade. This enzyme has yet to be studied in equine leukocytes, which
      play a pivotal role in equine inflammatory disease. The objective of this study
      was to determine if mPGES-1 is a PGE2-selective anti-inflammatory target in
      equine leukocytes. To evaluate this objective, leukocyte-rich plasma (LRP) was
      isolated from equine whole blood collected via jugular venipuncture of six
      healthy adult horses of mixed breeds and genders. LRP was primed with granulocyte
      monocyte colony-stimulating factor (GM-CSF) and stimulated with
      lipopolysaccharide (LPS) in the presence or absence of an mPGES-1 inhibitor
      (MF63), a COX-2 inhibitor (NS-398), or a nonselective COX inhibitor
      (indomethacin). Following treatment, mPGES-1 and COX-2 mRNA and protein levels
      were measured via qPCR and western blot, respectively, and PGE2, thromboxane
      (TXA2) and prostacyclin (PGI2) levels were measured in cellular supernatants via
      ELISA. This study revealed that LPS significantly increased mPGES-1 mRNA, but not
      protein levels in equine LRP as measured by qPCR and western blot, respectively.
      In contrast, COX-2 mRNA and protein were coordinately induced by LPS.
      Importantly, treatment of LPS-stimulated leukocytes with indomethacin and NS-398
      significantly reduced extracellular concentrations of multiple prostanoids (PGE2,
      TXA2 and PGI2), while the mPGES-1 inhibitor MF63 selectively inhibited PGE2
      production only. mPGES-1 inhibition also preserved higher basal levels of PGE2
      production when compared to either COX inhibitor, which might be beneficial in a
      clinical setting. In conclusion, this work identifies mPGES-1 as a key regulator
      of PGE2 production and a PGE2-selective target in equine leukocytes. This study
      demonstrates that mPGES-1 is a potentially safer and effective therapeutic target
      for treatment of equine inflammatory disease when compared to traditional non
      steroidal anti-inflammatory drugs.

PMID- 29042015
TI  - Identification of monoclonal antibodies cross-reactive with bottlenose dolphin
      orthologues of the major histocompatibility complex and leukocyte differentiation
      molecules.
AB  - The slow progress in understanding immunotoxic effects of environmental
      contaminants and their influence on disease susceptibility in whales is largely
      due to the limited information available on the immune systems and immune
      function of species included in the Cetancodontamorpha clade. Studies in species
      in the other major clades included in the Artiodactylamorpha, Ruminantiamorpha,
      Suinamorpha, and Camelidamorpha have revealed the immune systems are similar, but
      not identical. The present study was undertaken to expand the available
      monoclonal antibody reagents needed to gain insight into the composition,
      function, and evolution of the immune system in Cetancodontamorpha, using the
      dolphin (Tursiops truncatus) as a model cetacean species. Screening of a set of
      mAbs that recognize highly conserved epitopes expressed on the major
      histocompatibility complex (MHC) and leukocyte differentiation molecules (LDMs)
      in cattle by flow cytometry revealed some of the mAbs recognize epitopes
      conserved on dolphin orthologues of MHC class I, MHC class II, CD11a, CD14, CD16,
      CD18, CD163 and CD172a. Comparison of the amino acid sequences of dolphin and
      bovine orthologues revealed limited changes in sequence have occurred during
      speciation, suggesting an approach for developing cross-reactive mAbs for use in
      cetacean research.

PMID- 29042016
TI  - Bacteria causing pyometra in bitch and queen induce neutrophil extracellular
      traps.
AB  - Neutrophils are capable of releasing their DNA in response to infectious agents
      to form neutrophil extracellular traps (NETs) to destroy pathogens. Even though
      pyometra in queens and bitches is a common disease, its pathogenesis is not fully
      understood. The aim of this study was to assess the presence of NETs in the
      endometrium of queens and bitches suffering from pyometra. Pyometra and normal
      uteri were obtained after ovariohysterectomy from adult queens and bitches in
      diestrus. Uterine contents were evaluated for bacterial isolation and
      identification and for NETs presence. Escherichia coli were isolated in 5/5
      queens and 4/5 bitches, and Streptococcus spp in one bitch. Sterile glass
      coverslips were placed on the endometrium surface to obtain material for NETs
      that were evaluated by immunocytochemistry (histone, neutrophil elastase or
      myeloperoxidase), fluorescence microscopy or scanning electron microscopy. NETs
      in endometrium content were positively stained by DNA histone DAPI,
      myeloperoxidase and by neutrophil elastase. NETs were spread in all observed
      queen and bitch endometria of pyometra cases. Ultrastructure images of NETs
      depicted clusters of globular material with fine filaments deposited on or around
      thick filaments and trapped bacteria. To the best of our knowledge these are the
      first findings confirming NETs endometrial presence in queen and bitch pyometra.
      Nevertheless, the precise role of NETs in pyometra in the bitch and queen, either
      to contribute to the defeat of infection or to its persistence remains to be
      unraveled.

PMID- 29042017
TI  - Defending the selective confirmation strategy.
AB  - Most scientific realists today in one way or another confine the object of their
      commitment to certain components of a successful theory and thereby seek to make
      realism compatible with the history of theory change. Kyle Stanford calls this
      move by realists the strategy of selective confirmation and raises a challenge
      against its contemporary, reliable applicability. In this paper, I critically
      examine Stanford's inductive argument that is based on past scientists' failures
      to identify the confirmed components of their contemporary theories. I argue that
      our ability to make such identification should be evaluated based on the
      performance of the scientific community as a whole rather than that of individual
      scientists and that Stanford's challenge fails to raise a serious concern because
      it focuses solely on individual scientists' judgments, which are either made
      before the scientific community has reached a consensus or about the value of the
      posit as a locus for further research rather than its confirmed status.

PMID- 29042018
TI  - Was Feyerabend an anarchist? The structure(s) of 'anything goes'.
AB  - The near consensus in the secondary literature on Feyerabend is that his
      epistemological anarchism, characterized by the slogan 'anything goes', was not a
      positive proposal but the conclusion of a reductio argument against his opponents
      (Lloyd 1997; Staley 1999; Munevar 2000; Farrell 2003; Tsou 2003; Oberheim 2006;
      Roe 2009). This makes anarchism a mere criticism rather than a substantive
      position in its own right. In this paper, I argue that Feyerabend held anarchism
      as a positive thesis. Specifically, I present two possible interpretations of
      anarchism: one where anarchism is entailed by Feyerabend's radical view of
      pluralism and another where scientists must be 'methodological opportunists',
      which Feyerabend held simultaneously from at least 1970. I then consider how
      these positions fare against the more influential criticisms of anarchism (Nagel
      1977; Worrall 1978; Godfrey-Smith 2003). I conclude by suggesting two avenues to
      constraining a literal interpretation of 'anything goes' on Feyerabendian
      grounds.

PMID- 29042019
TI  - Duhemian good sense and agent reliabilism.

PMID- 29042020
TI  - Kuhnian theory-choice and virtue convergence: Facing the base rate fallacy.
AB  - Perhaps the strongest argument for scientific realism, the no-miracles-argument,
      has been said to commit the so-called base rate fallacy. The apparent elusiveness
      of the base rate of true theories has even been said to undermine the rationality
      of the entire realism debate. On the basis of the Kuhnian picture of theory
      choice, I confront this challenge by arguing that a theory is likely to be true
      if it possesses multiple theoretical virtues and is embraced by numerous
      scientists-even when the base rate converges to zero.

PMID- 29042021
TI  - Fresnel's laws, ceteris paribus.
AB  - This article is about structural realism, historical continuity, laws of nature,
      and ceteris paribus clauses. Fresnel's Laws of optics support Structural Realism
      because they are a scientific structure that has survived theory change. However,
      the history of Fresnel's Laws which has been depicted in debates over realism
      since the 1980s is badly distorted. Specifically, claims that J. C. Maxwell or
      his followers believed in an ontologically-subsistent electromagnetic field, and
      gave up the aether, before Einstein's annus mirabilis in 1905 are indefensible.
      Related claims that Maxwell himself did not believe in a luminiferous aether are
      also indefensible. This paper corrects the record. In order to trace Fresnel's
      Laws across significant ontological changes, they must be followed past Einstein
      into modern physics and nonlinear optics. I develop the philosophical
      implications of a more accurate history, and analyze Fresnel's Laws' historical
      trajectory in terms of dynamic ceteris paribus clauses. Structuralists have not
      embraced ceteris paribus laws, but they continue to point to Fresnel's Laws to
      resist anti-realist arguments from theory change. Fresnel's Laws fit the standard
      definition of a ceteris paribus law as a law applicable only in particular
      circumstances. Realists who appeal to the historical continuity of Fresnel's Laws
      to combat anti-realists must incorporate ceteris paribus laws into their
      metaphysics.

PMID- 29042022
TI  - State of the field: Paper tools.
AB  - Paper occupies a special place in histories of knowledge. It is the substrate of
      communication, the stuff of archives, the bearer of marks that make worlds. For
      the early-modern period in particular we now have a wealth of studies of 'paper
      tools', of the ways in which archives were assembled and put to use, of the
      making of lists and transcribing of observations, and so on. In other fields,
      too, attention has turned to the materiality of information. How far is it
      possible to draw a stable methodology out of the insights of literary and book
      historians, bibliographers, anthropologists, and those working in media studies?
      Do these diverse fields in fact refer to the same thing when they talk of paper,
      its qualities, affordances and limitations? In attempting to answer these
      questions, the present essay begins in the rich territory of early-modern natural
      philosophy - but from there opens out to take in recent works in a range of
      disciplines. Attending to the specific qualities of paper is only possible, I
      argue, if it is understood that paper can be both transparent and opaque
      depending on the social world it inhabits and helps to constitute. Paper flickers
      into and out of view, and it is precisely this quality that constitutes its
      sociomateriality.

PMID- 29042023
TI  - Selective embolization of the superior rectal artery: An alternative to
      hemorrhoid surgery?

PMID- 29042024
TI  - The role of the LTB4-BLT1 axis in chemotactic gradient sensing and directed
      leukocyte migration.
AB  - Directed leukocyte migration is a hallmark of inflammatory immune responses.
      Leukotrienes are derived from arachidonic acid and represent a class of potent
      lipid mediators of leukocyte migration. In this review, we summarize the
      essential steps leading to the production of LTB4 in leukocytes. We discuss the
      recent findings on the exosomal packaging and transport of LTB4 in the context of
      chemotactic gradients formation and regulation of leukocyte recruitment. We also
      discuss the dynamic roles of the LTB4 receptors, BLT1 and BLT2, in mediating
      chemotactic signaling in leukocytes and contrast them to other structurally
      related leukotrienes that bind to distinct GPCRs. Finally, we highlight the
      specific roles of the LTB4-BLT1 axis in mediating signal-relay between
      chemotaxing neutrophils and its potential contribution to a wide variety of
      inflammatory conditions including tumor progression and metastasis, where LTB4 is
      emerging as a key signaling component.

PMID- 29042025
TI  - Biosynthesis of leukotriene B4.
AB  - Leukotriene B4 (LTB4) is a lipid mediator derived from arachidonic acid (AA) by
      the sequential action of 5-lipoxygenase (5-LOX), 5-lipoxygenase-activating
      protein (FLAP) and LTA4 hydrolase (LTA4H). It was initially recognized for its
      involvement in the recruitment of neutrophils and is one of the most potent
      chemotactic agents known to date. A large body of data has indicated that LTB4
      plays a significant role in many chronic inflammatory diseases, such as
      arthritis, chronic obstructive pulmonary disease (COPD), cardiovascular disease,
      cancer and more recently, metabolic disorder. In this review, we focus on the
      biosynthesis of LTB4 and its biological effects. In particular, we will describe
      a basic biochemical understanding integrated with recent developments in the
      field of structural biology of the three key enzymes (5-LOX, FLAP and LTA4H) in
      LTB4 biosynthesis, and also summarize the most outstanding work on in vivo
      biological and pathogenic roles of these enzymes and the development of enzyme
      inhibitors.

PMID- 29042026
TI  - Identification, signaling, and functions of LTB4 receptors.
AB  - Leukotriene B4 (LTB4), a lipid mediator produced from arachidonic acid, is a
      chemoattractant for inflammatory leukocytes. We identified two receptors for
      LTB4, the high-affinity receptor BLT1 and the low-affinity receptor BLT2. BLT1 is
      expressed in various subsets of leukocytes, and analyses of BLT1-deficient mice
      revealed that the LTB4/BLT1 axis enhances leukocyte recruitment to infected
      sites, and is involved in the elimination of pathogens. Hyperactivation of the
      LTB4/BLT1 axis induces acute and chronic inflammation, resulting in various
      inflammatory diseases. BLT2 was originally identified as a low-affinity receptor
      for LTB4, and we later identified 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid
      (12-HHT) as a high-affinity ligand for BLT2. BLT2 is highly expressed in
      epithelial cells in various tissues including intestine and skin. Large
      quantities of 12-HHT are produced by activated platelets during skin injury, and
      activation of BLT2 on epidermal keratinocytes accelerates skin wound healing by
      enhancing cell migration. BLT2 signaling also enhances cell-cell junctions,
      protectes against transepidermal water loss, and preventes entry of environmental
      substances into the body.

PMID- 29042027
TI  - Too much of a good thing: How modulating LTB4 actions restore host defense in
      homeostasis or disease.
AB  - The ability to regulate inflammatory pathways and host defense mechanisms is
      critical for maintaining homeostasis and responding to infections and tissue
      injury. While unbalanced inflammation is detrimental to the host; inadequate
      inflammation might not provide effective signals required to eliminate pathogens.
      On the other hand, aberrant inflammation could result in organ damage and impair
      host defense. The lipid mediator leukotriene B4 (LTB4) is a potent neutrophil
      chemoattractant and recently, its role as a dominant molecule that amplifies many
      arms of phagocyte antimicrobial effector function has been unveiled. However,
      excessive LTB4 production contributes to disease severity in chronic inflammatory
      diseases such as diabetes and arthritis, which could potentially be involved in
      poor host defense in these groups of patients. In this review we discuss the
      cellular and molecular programs elicited during LTB4 production and actions on
      innate immunity host defense mechanisms as well as potential therapeutic
      strategies to improve host defense.

PMID- 29042029
TI  - LTB4 and BLT1 in inflammatory arthritis.
AB  - Inflammatory arthritis, including rheumatoid arthritis (RA), is characterized by
      infiltration of inflammatory cells into the joints. Biological agents targeting
      TNF-alpha and IL-6 dramatically improve RA. However, some RA patients do not
      respond to current treatments and these broadly active upstream biological agents
      increase the risk of severe infection. Therefore, there remains a need for other
      effective and safe treatments for RA. Many studies have implicated that blockade
      of leukotriene B4 (LTB4) and its high affinity receptor BLT1 dramatically
      suppress arthritis in animal models. In addition, levels of LTB4 in serum,
      synovial fluid and synovial tissue are increased in RA patients compared to
      healthy donors or osteoarthritis patients. These data suggest that LTB4 and BLT1
      likely contribute to the pathogenesis of human RA. However, several clinical
      trials inhibiting BLT1 in RA were not successful. Our recent data revealed that
      LTB4 is a key mediator in a complement, lipid, cytokine and chemokine cascade
      that first initiates and then sustains neutrophilic inflammation in inflammatory
      arthritis. These new mechanistic studies suggest novel ways to target the LTB4
      BLT1 pathway for the treatment of RA and other inflammatory diseases.

PMID- 29042028
TI  - Importance of the leukotriene B4-BLT1 and LTB4-BLT2 pathways in asthma.
AB  - For several decades, the leukotriene pathways have been implicated as playing a
      central role in the pathophysiology of asthma. The presence and elevation of
      numerous metabolites in the blood, sputum, and bronchoalveolar lavage fluid from
      asthmatics or experimental animals adds support to this notion. However,
      targeting of the leukotriene pathways has had, in general, limited success. The
      single exception in asthma therapy has been targeting of the cysteinyl
      leukotriene receptor 1, which clinically has proven effective but only in certain
      clinical situations. Interference with 5-lipoxygenase has had limited success, in
      part due to adverse drug effects. The importance of the LTB4-BLT1 pathway in
      asthma pathogenesis has extensive experimental support and findings, albeit
      limited, from clinical samples. The LTB4-BLT1 pathway was shown to be important
      as a neutrophil chemoattractant. Despite observations made more than two decades
      ago, the LTB4-BLT1 pathway has only recently been shown to exhibit important
      activities on subsets of T lymphocytes, both as a chemoattractant and on
      lymphocyte activation, as well as on dendritic cells, the major antigen
      presenting cell in the lung. The role of BLT2 in asthma remains unclear.
      Targeting of components of the LTB4-BLT1 pathway offers innovative therapeutic
      opportunities especially in patients with asthma that remain uncontrolled despite
      intensive corticosteroid treatment.

PMID- 29042030
TI  - Recent advances in clinical development of leukotriene B4 pathway drugs.
AB  - The LTB4 pathway is an attractive target for therapeutic drug development. Two
      broad classes of drugs have been pursued: antagonists of the primary LTB4
      receptors (BLT1 and BLT2) and inhibitors of LTA4 Hydrolase (LTA4H), the rate
      limiting enzyme in the production of LTB4. An initial wave of effort culminated
      in the 1990s. Over the past 15 years, a second wave of more selective drug
      candidates, including at least 5 BLT antagonists and 6 LTA4H inhibitors, have
      reached Phase 2 clinical trials. Despite the extensive efforts to discover and
      develop LTB4 pathway targeting drugs, only one has reached the market to date.
      Recently discovered complexities in the pathway and challenges in matching
      pathway intervention with therapeutic effect could explain the limited clinical
      success of LTB4 pathway drugs, even though there is a large body of scientific
      evidence linking LTB4 to human diseases and demonstrating efficacy of these
      compounds in a wide array of preclinical models. Herein, we describe the clinical
      programs for the most prominent recent examples from each broad class and discuss
      the clinical outcomes and their implications for future development of LTB4
      pathway drugs.

PMID- 29042031
TI  - Relation of the Mitral Annular Plane Systolic Excursion to Risk for Intervention
      in Initially Asymptomatic Patients With Aortic Stenosis and Preserved Systolic
      Function.
AB  - Aortic valve intervention (AVI) in patients with a severe aortic stenosis (AS)
      and a preserved left ventricular ejection fraction (LVEF) is controversial.
      Mitral annular plane systolic excursion (MAPSE) is an easily acquired metric of
      left ventricular longitudinal shortening. We sought to investigate if an
      asymptomatic decrease in MAPSE preceded the need for AVI in asymptomatic patients
      with AS and a preserved LVEF. In this retrospective cohort study, we identified
      205 consecutive patients (56% male, 73 +/- 11 years) with at least a moderate AS
      and a normal LVEF who underwent a serial outpatient transthoracic
      echocardiography (TTE) from 2006 to 2013. Apical TTE images were reviewed and
      (the average of septal, lateral, anterior, and inferior) MAPSE was measured. We
      examined the association of change in MAPSE with aortic valve area and LVEF over
      time and used time-varying Cox models to examine the risk of AVI. MAPSE
      correlated with aortic valve area (Spearman r = 0.18, p = 0.02) and decreased
      with subsequent TTE, whereas LVEF was "maintained." For each 1-mm reduction in
      MAPSE, the age- and gender-adjusted hazard ratio (HR) for AVI was 1.15 (95%
      confidence interval [CI] 1.01 to 1.31, p = 0.04). A MAPSE decrease of >2 mm/TTE
      was significantly associated with an increased risk of AVI, with an adjusted HR
      of 1.95 (95% CI 1.04 to 3.66, p = 0.04), whereas a MAPSE decrease of >1.5 mm/year
      trended toward an association with an increased risk of AVI (HR 1.61, 95% CI 0.95
      to 2.74, p = 0.08). In conclusion, in asymptomatic patients with at least a
      moderate AS and a preserved LVEF, an asymptomatic decrease in MAPSE was
      associated with the clinical need for AVI despite ongoing preservation of LVEF.

PMID- 29042032
TI  - Clinical outcomes and predictors of patient satisfaction in displaced midshaft
      clavicle fractures in adults: Results from a retrospective multicentre study.
AB  - BACKGROUND: The optimal treatment of displaced midshaft clavicle fractures
      (Robinson Type 2B1 & 2B2) in adults remains controversial. Little is known about
      patient satisfaction with treatment for this type of injury. The purpose of this
      study was to compare clinical outcomes and explore predictors of patient
      satisfaction after nonoperative and direct-operative treatment of displaced
      midshaft clavicle fractures in adults. METHODS: A retrospective multicentre study
      was conducted. Clinical data were retrieved from electronic patient charts. A
      questionnaire informing on current subjective function (QuickDASH), pain levels
      (VAS), health-related quality of life (Eq-5D-5L), impact on employment and
      satisfaction with treatment results was sent to all patients. Univariate and
      multivariate linear regression was performed to identify predictors of
      satisfaction. RESULTS: A total of 278 patients were identified (nonoperative
      n=150, direct-operative n=128). 67% of eligible patients returned the
      questionnaire. Median questionnaire follow-up was 2.1 years. No differences were
      found between groups for QuickDASH, Eq-5D-5L or pain VAS scores. Impaired union
      was observed in 13.2% of nonoperative cases vs. 2.3% in the direct-operative
      group. Patients in the nonoperative group could resume work after a median of
      30.0days, compared to 13.5days in the direct-operative group. Patient
      satisfaction was higher in the direct-operative group, 8/10 vs. 7/10 for overall
      treatment results respectively. Patients' rating for the level of shared decision
      making was the main predictor of overall satisfaction. CONCLUSION: Direct
      operative management led to higher patient satisfaction, despite similar long
      term patient reported outcomes with nonoperative treatment. Patients' rating for
      the level of shared decision-making was the main predictor of overall
      satisfaction. This study highlights the need to enhance communication to
      facilitate shared decision-making.

PMID- 29042033
TI  - Serious game training improves performance in combat life-saving interventions.
AB  - AIM: In modern warfare, almost 25% of combat-related deaths are considered
      preventable if life-saving interventions are performed. Therefore, Tactical
      Combat Casualty Care (TCCC) training for soldiers is a major challenge. In 2014,
      the French Military Medical Service supported the development of 3D-SC1(r), a
      serious game designed for the French TCCC program, entitled Sauvetage au Combat
      de niveau 1 (SC1). Our study aimed to evaluate the impact on performance of
      additional training with 3D-SC1(r). MATERIAL AND METHODS: The study assessed the
      performance of soldiers randomly assigned to one of two groups, before (measure
      1) and after (measure 2) receiving additional training. This training involved
      either 3D-SC1(r) (Intervention group), or a DVD (Control group). The principal
      measure was the individual performance (on a 16-point scale), assessed by two
      investigators during a hands-on simulation. First, the mean performance score was
      compared between the two measures for Intervention and Control groups using a two
      tailed paired t-test. Second, a multivariable linear regression was used to
      determine the difference in the impacts of 3D-SC1(r) and DVD training, and the
      order of presentation of the two scenarios, on the mean change from baseline in
      performance scores. RESULTS AND DISCUSSION: A total of 96 subjects were
      evaluated: seven could not be followed-up, while 50 were randomly allocated to
      the Intervention group, and 39 to the Control group. Between measure 1 and
      measure 2, the mean (SD) performance score increased from 9.9 (3.13) to 14.1
      (1.23), and from 9.4 (2.97) to 12.5 (1.83), for the Intervention group and
      Control group, respectively (p<0.0001). The adjusted mean difference in
      performance scores between 3D-SC1(r) and DVD training was 1.1 (95% confidence
      interval -0.3, 2.5) (p=0.14). Overall, the study found that supplementing SC1
      training with either 3D-SC1(r) or DVD improved performance, assessed by a hands
      on simulation. However, our analysis did not find a statistically significant
      difference between the effects of these two training tools. 3D-SC1(r) could be an
      efficient and pedagogical tool to train soldiers in life-saving interventions. In
      the current context of terrorist threat, a specifically-adapted version of 3D
      SC1(r)may be a cost-effective and engaging way to train a large civilian public.

PMID- 29042034
TI  - Evaluation of mandibular fracture healing in rats under zoledronate therapy: A
      histologic study.
AB  - INTRODUCTION: To evaluate fracture healing in mandible of rats under zoledronate
      therapy. METHODS: A total of 135 Wistar rats were randomly allocated into 3
      groups. Group L received two intravenous infusion of 0.06 mg/kg zoledronate 6
      weeks apart. Group H received the same dose of zoledronate as group L once a week
      for 6 weeks and group C were treated with normal saline. Seven days after the
      last infusion, rats underwent unilateral mandibular osteotomy to replicate a
      fracture. Fifteen rats from each group were sacrificed 2, 4, and 6 weeks after
      surgery. Fracture calluses were examined and scored using a histological grading
      system (1 to 10). RESULTS: After 2 weeks, substantial woven bone and some
      lamellar bone were seen in control and L groups. In group H, healing was delayed
      and consisted of fibrous and cartilaginous tissue and some woven bone. After 4
      weeks, most of woven bone in control group was replaced with lamellar bone but in
      group L, comparatively less bone remodeling occurred. In group H, healing process
      was nearly the same as that at 2 weeks. After 6 weeks, complete bone remodeling
      was seen in control group. In group L, bone remodeling was under way and in group
      H, histological findings were nearly the same as those at 2 and 4 weeks. Except
      for L and control groups at 2 weeks, healing score was significantly different
      between all corresponding groups. CONCLUSION: Zoledronate therapy delayed healing
      process of mandibular fracture in rats in a dose-dependent manner.

PMID- 29042035
TI  - A systematic review of molecular responses to cancer therapy in normal human
      mucosa.
AB  - OBJECTIVE: Cancer therapy-induced inflammation of oral and gastrointestinal
      mucosae affects patients nonuniformly. Preventive strategies are limited; no
      biomarker exists for pretreatment identification of patients likely to be
      severely affected. Animal models are preferred for studying molecular responses
      in mucosae during chemotherapy, but translation into clinical practice is
      difficult. We performed a systematic review to retrieve articles that described
      molecular changes in human mucosae during cancer therapy. STUDY DESIGN: We
      searched MEDLINE and Ovid Embase searches for studies reported in the English
      language literature from January 1990 to November 2016 and studies referenced in
      selected articles, which analyzed mucosae from patients at risk of developing
      mucositis during cancer therapy. Two authors extracted data according to
      predefined data fields, including study quality indicators. RESULTS: We
      identified 17 human studies on chemotherapy (n = 9) and radiotherapy (n = 8), but
      no studies on targeted therapy. Studies were heterogeneous with regard to patient
      cohorts, analysis methods, cancer treatments, biopsy timings, and correlations to
      clinical mucositis. Consequently, a meta-analysis was not feasible. CONCLUSIONS:
      Few human studies described the molecular responses of the normal mucosa to
      cancer therapy. Studies were heterogeneous and had sparse correlations to
      clinical mucositis. We proposed a model for acquiring data on treatment- and
      disease-specific phenotypes and transcriptomes for predictive or preventive
      initiatives.

PMID- 29042036
TI  - New logos.

PMID- 29042037
TI  - No rat poison for me.

PMID- 29042038
TI  - Rapid-deployment aortic valve systems: The surgeons' alternative to transcatheter
      aortic valve implantation?

PMID- 29042039
TI  - Rapid deployment aortic valve systems: The surgeons' alternative to Transcatheter
      Aortic Valve Implantation?

PMID- 29042041
TI  - Discussion.

PMID- 29042042
TI  - A stitch too far: The circumflex artery in jeopardy during mitral valve repair.

PMID- 29042043
TI  - The case for surgical myectomy in hypertrophic cardiomyopathy: Is strategic
      planning the key to success?

PMID- 29042040
TI  - Optimal blood pressure during cardiopulmonary bypass defined by cerebral
      autoregulation monitoring.
AB  - OBJECTIVES: We sought to define the lower and upper limits of cerebral blood flow
      autoregulation and the optimal blood pressure during cardiopulmonary bypass. We
      further sought to identify variables predictive of these autoregulation end
      points. METHODS: Cerebral autoregulation was monitored continuously with
      transcranial Doppler in 614 patients during cardiopulmonary bypass enrolled in 3
      investigations. A moving Pearson's correlation coefficient was calculated between
      cerebral blood flow velocity and mean arterial pressure to generate the variable
      mean velocity index. Optimal mean arterial pressure was defined as the mean
      arterial pressure with the lowest mean velocity index indicating the best
      autoregulation. The lower and upper limits of cerebral blood flow autoregulation
      were defined as the mean arterial pressure at which mean velocity index was
      increasingly pressure passive (ie, mean velocity index >=0.4) with declining or
      increasing blood pressure, respectively. RESULTS: The mean (+/- standard
      deviation) lower and upper limits of cerebral blood flow autoregulation, and
      optimal mean arterial pressure were 65 +/- 12 mm Hg, 84 +/- 11 mm Hg, and 78 +/-
      11 mm Hg, respectively, after adjusting for study enrollment. In 17% of patients,
      though, the lower limit of cerebral autoregulation was above this optimal mean
      arterial pressure, whereas in 29% of patients the upper limit of autoregulation
      was below the population optimal mean arterial pressure. Variables associated
      with optimal mean arterial pressure based on multivariate regression analysis
      were nonwhite race (increased 2.7 mm Hg; P = .034), diuretics use (decreased 1.9
      mm Hg; P = .049), prior carotid endarterectomy (decreased 5.5 mm Hg; P = .019),
      and duration of cardiopulmonary bypass (decreased 1.28 per 60 minutes of
      cardiopulmonary bypass). The product of the duration and magnitude that mean
      arterial pressure during cardiopulmonary bypass was below the lower limit of
      cerebral autoregulation was associated with the risk for stroke (P = .02).
      CONCLUSIONS: Real-time monitoring of autoregulation may improve individualizing
      mean arterial pressure during cardiopulmonary bypass and improving patient
      outcomes.

PMID- 29042044
TI  - In these "good times," it can still be "diff'rent strokes" for different folks.

PMID- 29042045
TI  - It's not about "can we" but "should we".

PMID- 29042046
TI  - Ancillary revelations of the Single-Ventricle Reconstruction Trial: The less
      excitement, the better.

PMID- 29042047
TI  - An aspirin a day may not be enough.

PMID- 29042048
TI  - The right ventricle in the systemic circulation: Why do some fail?

PMID- 29042050
TI  - Scoring system to predict nodal metastases in patients with early-stage
      esophageal cancer: An outstanding tool to complement multidisciplinary, team
      based care.

PMID- 29042049
TI  - T category of non-small cell lung cancer invading the fissure to the adjacent
      lobe.
AB  - BACKGROUND: Dispute arises in the tumor category of non-small cell lung cancer
      invading the fissure to the adjacent lobe. The purpose of this study is to
      determine the long-term prognosis of non-small cell lung cancer with such an
      invasion and to propose an appropriate T category. METHODS: In total, 53 cases of
      non-small cell lung cancer invading the fissure to the adjacent lobe (fissure
      group) were identified in patients who underwent pulmonary resection from 1997 to
      2014. Propensity score matching was applied to balance known confounders for
      prognosis between each paired group, resulting in 3 matched sets (fissure vs T2a,
      fissure vs T2b, and fissure vs T3). The overall survival of the fissure group was
      compared with the survival of patients with T2a, T2b, and T3 diseases, as
      classified in the eighth edition of TNM classification. RESULTS: The 5-year
      survivals of the T2a, T2b, T3, and fissure groups were 64.2% (95% confidence
      interval, 53.2-72.6), 54.6% (95% confidence interval, 44.7-65.8), 35.8% (95%
      confidence interval, 22.8-44.2), and 38.6% (95% confidence interval, 25.0-52.2),
      respectively. Specifically, the difference between the fissure group and T2a is
      statistically significant at P = .01; between the fissure group and T2b at P =
      .02; and between the fissure group and T3 at P = .93. Multivariate analyses
      indicate that the fissure group had a similar risk of dying as the T3 disease
      group (hazard ratio, 1.10; 95% confidence interval, 0.69-1.37) and was at a
      significantly higher risk compared with the T2a group (hazard ratio, 2.34; 95%
      confidence interval, 1.50-3.39) and T2b group (hazard ratio, 1.71; 95% confidence
      interval, 1.19-2.76). CONCLUSIONS: On the basis of our single-institution study,
      we propose that non-small cell lung cancer invading the fissure to the adjacent
      lobe should be further investigated and the impact on patients' prognoses
      validated as a T3 disease.

PMID- 29042052
TI  - Discussion.

PMID- 29042051
TI  - Extracorporeal membrane oxygenation as a bridge to lung transplantation: A single
      center experience in the present era.
AB  - OBJECTIVE: Extracorporeal membrane oxygenation has been used as a bridge to lung
      transplantation in patients with rapid pulmonary function deterioration. The
      reported success of this modality and perioperative and functional outcomes are
      varied. METHODS: We retrospectively reviewed all patients who underwent lung
      transplantation at our institution over 1 year (January 1, 2015, to December 31,
      2015). Patients were divided into 2 groups depending on whether they required
      extracorporeal membrane oxygenation support as a bridge to transplant;
      preoperative characteristics, lung transplantation outcomes, and survival were
      compared between groups. RESULTS: Of the 93 patients, 12 (13%) received bridge to
      transplant, and 81 (87%) did not. Patients receiving bridge to transplant were
      younger, had higher lung allocation scores, had lower functional status, and were
      more often on mechanical ventilation at listing. Most patients who received
      bridge to transplant (n = 10, 83.3%) had pulmonary fibrosis. Mean pretransplant
      extracorporeal membrane oxygenation support was 103.6 hours in duration (range,
      16-395 hours). All patients who received bridge to transplant were decannulated
      immediately after lung transplantation but were more likely to return to the
      operating room for secondary chest closure or rethoracotomy. Grade 3 primary
      graft dysfunction within 72 hours was similar between groups. Lung
      transplantation success and hospital discharge were 100% in the bridge to
      transplant group; however, these patients experienced longer hospital stays and
      higher rates of discharge to acute rehabilitation. The 1-year survival was 100%
      in the bridge to transplant group and 91% in the non-bridge to transplant group
      (log-rank, P = .24). The 1-year functional status was excellent in both groups.
      CONCLUSIONS: Extracorporeal membrane oxygenation can be used to safely bridge
      high-acuity patients with end-stage lung disease to lung transplantation with
      good 30-day, 90-day, and 1-year survival and excellent 1-year functional status.
      Long-term outcomes are being studied.

PMID- 29042053
TI  - Hitting the target with lung perfusion.

PMID- 29042054
TI  - PREFACE: Special Issue on Advances in Industrial Bioprocesses and Products -
      Genetic and Metabolic Engineering Interventions.

PMID- 29042056
TI  - A computational model of the hepatic circulation applied to analyze the
      sensitivity of hepatic venous pressure gradient (HVPG) in liver cirrhosis.
AB  - Measurement of hepatic venous pressure gradient (HVPG) is currently widely
      adopted to provide an estimate of portal pressure gradient (PPG) in the diagnosis
      and treatment of portal hypertension associated with liver cirrhosis. Despite the
      well-documented clinical utility of HVPG, it remains poorly understood how the
      relationship between HVPG and PPG is affected by factors involved in the
      pathogenesis and progression of cirrhosis. In the study, a computational model of
      the hepatic circulation calibrated to in vivo data was developed to simulate the
      procedure of HVPG measurement and quantitatively investigate the error of HVPG
      relative to PPG under various pathophysiological conditions. Obtained results
      confirmed the clinical consensus that HVPG is applicable to the assessment of
      portal hypertension caused by increased vascular resistance located primarily at
      the sinusoidal and postsinusoidal sites rather than at the presinusoidal site. On
      the other hand, our study demonstrated that the accuracy of HVPG measurement was
      influenced by many factors related to hepatic hemodynamics even in the case of
      sinusoidal portal hypertension. For instance, varying presinusoidal portal
      vascular resistance significantly altered the difference between HVPG and PPG,
      while an enhancement in portosystemic collateral flow tended to improve the
      accuracy of HVPG measurement. Moreover, it was found that presinusoidal and
      postsinusoidal vascular resistances interfered with each other with respect to
      their influence on HVPG measurement. These findings suggest that one should take
      into account patient-specific pathological conditions in order to achieve a
      better understanding and utilization of HVPG in the clinical practice.

PMID- 29042055
TI  - Mechanism underlying the suppressor activity of retinoic acid on IL4-induced IgE
      synthesis and its physiological implication.
AB  - The present study extends an earlier report that retinoic acid (RA) down
      regulates IgE Ab synthesis in vitro. Here, we show the suppressive activity of RA
      on IgE production in vivo and its underlying mechanisms. We found that RA down
      regulated IgE class switching recombination (CSR) mainly through RA receptor
      alpha (RARalpha). Additionally, RA inhibited histone acetylation of germ-line
      epsilon (GL epsilon) promoter, leading to suppression of IgE CSR. Consistently,
      serum IgE levels were substantially elevated in vitamin A-deficient (VAD) mice
      and this was more dramatic in VAD-lecithin:retinol acyltransferase deficient
      (LRAT-/-) mice. Further, serum mouse mast cell protease-1 (mMCP-1) level was
      elevated while frequency of intestinal regulatory T cells (Tregs) were diminished
      in VAD LRAT-/- mice, reflecting that deprivation of RA leads to allergic immune
      response. Taken together, our results reveal that RA has an IgE-repressive
      activity in vivo, which may ameliorate IgE-mediated allergic disease.

PMID- 29042057
TI  - Urethral lumen occlusion by artificial sphincteric device: Evaluation of degraded
      tissues effects.
AB  - Urinary incontinence can be surgically treated by means of artificial sphincters,
      based on a cuff that provides a pressure around the urethra to occlude the lumen.
      Considering the frequent access of elderly patients to this surgical practice,
      tissue degradation phenomena must be investigated, since they could affect
      treatment reliability and durability. The potential degradation can be
      interpreted considering a variation within soft tissue constitutive formulation,
      by means of a correlation between mechanical properties and tissues ageing. The
      overall compressibility varies, as characteristics aspect of soft tissue
      mechanical response with age, as well as the stiffness. The investigation is
      performed by means of a three dimensional numerical model of the urethral duct.
      The effects of the interaction phenomenon with a cuff is interpreted considering
      the changes, within the constitutive models, of the basic parameters that define
      the potential degradation process. The deformation related to compressibility is
      recalled, ranging between ten and fifty percent in dependence on the degradation
      level considered. This parameter, reported mostly as representative of the aging
      effect, shows a large variation that confirms the relevance of the investigation
      performed toward a sensitivity of the mechanical response of the urethral duct
      referred to the lumen occlusion.

PMID- 29042058
TI  - Exercise induced complete atrioventricular block: Utility of exercise stress
      test.
AB  - Exercise induced complete atrioventricular block (EIAVB) is a relatively uncommon
      condition. This phenomenon is clinically important because it can mimic symptoms
      of other cardiovascular conditions and may be associated with exercise
      intolerance and subsequent syncope. A 76year old man with long-standing
      hypertension and diabetes mellitus presented with recurrent episodes of
      lightheadedness and syncope with physical activity. ECG showed sinus rhythm with
      first degree atrioventricular block. Echocardiography did not show any valvular
      disease causing his symptoms. Coronoary angiographic evaluation revealed non
      obstructive coronary artery disease. Because of the exertional nature of his
      symptoms, a symptom-limited treadmill exercise test was performed which revealed
      EIAVB. A permanent dual chamber pacemaker was implanted and his symptoms resolved
      completely.

PMID- 29042059
TI  - Histamine, paroxysmal AV block and low adenosine syncope a case report.

PMID- 29042060
TI  - Australian general practitioners initiate statin therapy primarily on the basis
      of lipid levels; New Zealand general practitioners use absolute risk.
AB  - OBJECTIVES: To compare the determinants of initial statin prescribing between New
      Zealand and Australia. New Zealand has a system-wide absolute risk-based approach
      to primary care cardiovascular disease (CVD) management, while Australia has
      multiple guidelines. METHOD: Classification and Regression Tree (CART) analysis
      of two observational studies of primary care CVD management from New Zealand
      (PREDICT-CVD) and Australia (AusHeart). Over 80% of eligible New Zealanders have
      been screened for CVD risk. PREDICT-CVD is used by approximately one-third of New
      Zealand GPs to perform web-based CVD risk assessment in routine practice, with
      the sample consisting of 126,519 individuals risk assessed between 1 January 2007
      and 30 June 2014. AusHeart is a cluster-stratified survey of primary care CVD
      management that enrolled 534 GPs from across Australia, who in turn recruited
      1381 patients between 1 April and 30 June 2008. Eligibility was restricted to 55
      74year old patients without prior CVD. RESULTS: The CART analyses demonstrated
      that New Zealand GPs prescribe statins primarily on the basis of absolute risk,
      while their Australian counterparts are influenced by a variety of individual
      risk factors, including total cholesterol, LDL cholesterol and diabetes.
      CONCLUSIONS: Countries seeking to improve their management of CVD should consider
      adopting a 'whole of system' absolute risk-based approach with clear guidelines
      that are consistent with drug reimbursement rules; and include computerized
      decision-support tools that aid decision-making and allow monitoring of outcomes
      and continual improvement of practice.

PMID- 29042061
TI  - Analysis of selected aspects of inflammasome function in the monocytes from
      neonates born extremely and very prematurely.
AB  - BACKGROUND: Inflammasomes regulate activation of caspase-1, which cleaves and
      activates interleukin (IL)-1beta and IL-18, the cytokines that trigger pro
      inflammatory and antimicrobial responses. There is very little known about
      inflammasome function in the subsets of monocytes (MO) isolated from preterm
      neonates born extremely and very prematurely. METHODS: A group of 76 very low
      birth weight patients without early-onset sepsis was divided into extremely
      preterm (<28 gestational week) or very preterm (28-32 gestational week) neonates.
      The first blood sample was collected on the 5th day of life (5th DOL) to analyse
      MO subsets as well as the intracellular IL-1beta expression and supernatant
      concentration of IL-1beta and IL-18. Secondary blood samples were collected
      within 24h of late-onset sepsis (LOS) development and analysed as above. RESULTS:
      On the 5th DOL, the extremely preterm neonates were characterized by a
      significantly higher absolute count of MO, in particular in the classical and
      intermediate subsets, as compared to the very preterm group. The counts of the
      intermediate and non-classical MO subsets increased during LOS in all neonates.
      We did not observe significant differences in the intracellular IL-1beta
      expression between the analysed groups. Furthermore, the levels of the analysed
      cytokines in the MO supernatants were comparable between the extremely and very
      preterm neonates on the 5th DOL. Finally, a higher level of IL-18 was observed in
      the supernatant of the extremely preterm group during LOS. CONCLUSIONS: During
      LOS, extremely preterm neonates excrete a higher level of IL-18 cytokines
      compared to very preterm neonates. Further studies are required to determine
      whether this observation is a result of a higher count of the circulating MO or
      is a true reflection of increased inflammasome function in this particular group
      of newborns.

PMID- 29042062
TI  - Getting evidence into action to tackle institutional child abuse.
AB  - The Australian Royal Commission into Institutional Responses to Child Sexual
      Abuse is an example of a government response to survivors' demands to address the
      harm they suffered. It is also a major response by a national government to
      improve child safety in the future. Facing up to child abuse is difficult and in
      other countries similar inquiries have suffered delays and derailing. This
      commentary uses an evidence-to-action lens to explore why clear evidence of child
      sexual abuse may be ignored and side-lined. It argues that where evidence
      challenges the powerful, is surprising and shocking, or undercuts current
      institutional and policy arrangements, then that evidence is likely to be
      ignored, undermined or refuted - all factors which are present in the case of
      historical institutional child sexual abuse.

PMID- 29042064
TI  - Botulinum toxin therapy as an early intervention for post-stroke spasticity:
      Beyond a functional viewpoint.

PMID- 29042063
TI  - [Pharmacokinetic and clinical effects of two bupivacaine concentrations on
      axillary brachial plexus block].
AB  - INTRODUCTION: The risk of systemic bupivacaine toxicity is a persistent problem,
      which makes its pharmacokinetic study fundamental for regional anesthesia safety.
      There is little evidence of its influence on plasma peak at different
      concentrations. The present study compares two bupivacaine concentrations to
      establish how the concentration affects this drug plasma peak in axillary
      brachial plexus block. Postoperative latency and analgesia were also compared.
      METHODS: 30 patients were randomized. In the 0.25% Group, 0.25% bupivacaine
      (10mL) was injected per nerve. In the 0.5% Group, 0.5% bupivacaine (5mL) was
      injected per nerve. Peripheral blood samples were collected during the first
      2hours after the blockade. For sample analyses, high performance liquid
      chromatography mass spectrometry was used. RESULTS: Plasma peak occurred
      45minutes after the blockade, with no difference between groups at the assessed
      time-points. Plasma peak was 933.97 +/- 328.03 ng.mL-1 (mean +/- SD) in 0.25%
      Group and 1022.79 +/- 253.81 ng.mL-1 in 0.5% Group (p = 0.414). Latency was lower
      in 0.5% Group than in 0.25% Group (10.67 +/- 3.71 * 17.33min +/- 5.30,
      respectively, p = 0.004). No patient had pain within the first 4hours after the
      blockade. CONCLUSION: For axillary brachial plexus block, there was no difference
      in bupivacaine plasma peak despite the use of different concentrations with the
      same local anesthetic mass. The concentration inversely influenced latency.

PMID- 29042065
TI  - Analgesic and anxiolytic effects of [Leu31,Pro34]-neuropeptide Y microinjected
      into the periaqueductal gray in rats.
AB  - Several reports have demonstrated that neuropeptide Y (NPY) is involved in food
      intake, epilepsy, circadian rhythms, drug seeking, pain and anxiety, and other
      physiological or pathological conditions. On the other hand, periaqueductal gray
      (PAG) is a key brain center for modulating pain, anxiety and fear. It is the main
      structure implicated in integrated defensive behaviors. One such behavior, tonic
      immobility (TI), resembles fear and is able to induce analgesia. After
      microinjection of [Leu31,Pro34]-Neuropeptide Y ([Leu31,Pro34]-NPY) into the PAG
      dorsal (D) or ventrolateral (VL) of adult male Wistar rats, the following
      parameters were assessed: i) the analgesic effect by means of the tail-flick test
      (TF), ii) the duration of TI as a passive defensive behavioral response and as an
      anxiety/fear model (considering both TF and TI as single behaviors), iii) TI
      induced analgesia by the combination of TF/TI, and iv) the anxious-like state
      through the elevated plus maze (EPM), and defensive burying behavior (DBB). The
      results show that the microinjection of [Leu31,Pro34]-NPY into the PAG produced
      an analgesic effect (increasing the TF latency); overall decreased the TI
      duration, which might represent an important anti-fear effect. Moreover,
      [Leu31,Pro34]-NPY microinjected into the PAG allows for a TI-induced analgesic
      effect, as well as, a substantial anxiolytic effect (evidenced by the EPM and DBB
      models). Hence, [Leu31,Pro34]-NPY microinjected into the PAG, especially at
      0.47nmol/0.5MUL produces both analgesic and anxiolytic effects, in a higher
      magnitude within ventrolateral area.

PMID- 29042066
TI  - LM and SEM study on the swordfish (Xiphias gladius) tongue.
AB  - Swordfish (Xiphias gladius L. 1758) is a predatory and migratory fish. Its
      characteristic feature is a flat and sharp upper jaw forming a "sword". The
      adaptation of vertebrates, including fish, to their environment is strictly
      related to the capacity of feeding and is carried out by often severe
      modifications of the anatomy of the buccal cavity, especially of the tongue. The
      aim of this study is, using light and scanning electron microscopy and
      considering that no data are so far available about the morphology of the tongue
      in this species, to analyse the anatomical characteristics of the tongue,
      especially its dorsal surface. The tongue shows a triangular shape and an apex, a
      body and a root. By SEM the presence of several small denticles and filiform
      papillae on the latero-ventral body was demonstrated while no taste buds or other
      sensitive structures are observed. LM shows a squamous stratified epithelium,
      becoming simple cuboidal around the denticles. Therefore this study could add
      further data to the knowledges of the fish oral cavity morphology supporting the
      hypothesis that the modifications and evolution of the tongue anatomy are, also
      in fish, related to the environment and especially to the feeding habits.

PMID- 29042067
TI  - Malignant external otitis: The shifting treatment paradigm.
AB  - IMPORTANCE: Malignant external otitis (MEO) is an aggressive infection occurring
      in immunocompromised hosts. Increasing antimicrobial resistance is making the
      disease more difficult to treat. OBJECTIVE: Determine if there has been a shift
      in the microbiology and outcomes of MEO. DESIGN: A retrospective case series at a
      tertiary care institution. SETTING: Inpatient and outpatient tertiary care
      hospital. PARTICIPANTS: 12 cases of recent MEO were reviewed. MAIN OUTCOMES AND
      MEASURES: The primary outcome was progression of disease. Secondary outcomes were
      drug resistance and complications of MEO. RESULTS: Only 4 patients were cured of
      MEO. Four patients expired during the study period and at least one of these
      deaths was a direct result of the MEO. 7 patients developed Cranial nerve
      palsies, and 3 patients developed abscesses. CONCLUSIONS: Select cases of MEO now
      require multi-drug and long-term parenteral antibiotic therapy with extended
      hospital stays.

PMID- 29042068
TI  - Reduction of bone mineral density in native Chinese female idiopathic benign
      paroxysmal positional vertigo patients.
AB  - OBJECTIVE: This study aimed to investigate the clinical association between
      idiopathic benign paroxysmal positional vertigo (BPPV) and reduction of bone
      mineral density (BMD). METHODS: BMD was measured in 78 native Chinese female de
      novo idiopathic BPPV patients and 126 healthy controls using dual-energy X-ray
      absorptiometry. We compared the mean T-scores and abnormal BMD prevalence between
      the two groups. RESULTS: The mean T-scores were significantly lower in idiopathic
      BPPV patients than in healthy controls. The prevalence of osteopenia and
      osteoporosis were significantly higher in idiopathic BPPV patients than in
      healthy controls (65.4% vs 48.4%, p=0.013). CONCLUSION: BMD reduction may be
      associated with idiopathic BPPV occurrence.

PMID- 29042069
TI  - Mind over bladder: Women, aging, and bladder health.
AB  - The purpose of this study was to explore the efficacy and acceptability of an
      innovative, electronically delivered self-management intervention for urinary
      incontinence (UI) that included daily mindfulness practice, completion of
      sequential bladder diaries, and bladder health education to improve UI in older
      women living independently in a retirement community. A mixed methods pilot study
      was conducted over ten weeks using a custom website or CD. Ten women were
      recruited and 8 completed the study; 5 of those (71%) experienced fewer daily UI
      episodes post intervention (p = 0.055). The women also reported a statistically
      significant decrease in the impact UI had on their everyday life (p = 0.04).
      Seventy-one percent (N = 5) reported subjective improvement in UI, and high
      acceptability scores also were achieved. The intervention was both effective in
      helping older women self-manage UI and acceptable to the population group.
      Further research is needed with a larger and diverse population of older women.

PMID- 29042070
TI  - Geriatric palliative care: Meeting the needs of a growing population.
AB  - The implementation of effective geriatric palliative care (PC) services will be
      increasingly important as the number of patients ages >=65 years continues to
      grow. However, literature characterizing the utilization of PC services by older
      adults remains scant. The objective of these analyses was to characterize the
      nature and outcomes of PC services for older adults. A retrospective analysis of
      records of inpatient PC consultations provided to patients >=65 years at an
      academic hospital was performed (N = 743). Logistic regressions identified
      factors associated with goals of care discussions (GOC), end-of-life (EOL)
      coordination, and hospital readmission. Differences between older adult subgroups
      (i.e., 65-84 years and 85 years and older) were also examined. Discharge to home
      was associated with higher odds of readmission and discharge to hospice or having
      a GOC discussion was associated with lower odds of readmission. Those patients
      who were 85 years or older were significantly less likely to have cancer or to be
      referred for pain management, and more likely to be referred for GOC discussions
      and discharged to hospice. This study revealed dynamic factors associated with PC
      consultation for older adults. GOC discussions in initial PC consultations for
      older patients might reduce the odds of hospital readmission. Additionally, the
      needs of patients ages 85 and older appear distinct from the traditional PC
      cancer model.

PMID- 29042071
TI  - Influence of Ginkgo Biloba extract (EGb 761) on expression of IL-1 Beta, IL-6,
      TNF-alfa, HSP-70, HSF-1 and COX-2 after noise exposure in the rat cochlea.
AB  - OBJECTIVE: The objective of this study was to investigate the influence of Ginkgo
      Biloba in early treatment of noise induced hearing loss on expression of IL-6, IL
      1 Beta, TNF-alfa, HSP-70, HSF-1 and COX-2 in the rat cochlea. METHODS: Thirty two
      female rats were randomly divided into four groups (Acoustic Trauma, Ginkgo
      Biloba, Acoustic Trauma+Ginkgo Biloba, Non Treatment). Auditory brainstem
      response (ABR) was applied in all the groups. At the end of the study, IL-1Beta,
      IL-6, TNF-alpha, HSP-70, HSF-1 and COX-2 were studied in cochlear tissue with
      ELISA and Western blot analysis. RESULTS: There were significant increases in ABR
      values measured at days 1 and 7 compared to baseline values in Group 3. IL-1
      Beta, IL-6 and TNF-alpha values were significantly higher in Group 1 than in the
      other groups. Whereas HSP-70 and HSF-1 values were found to be significantly
      lower in Group 1 compared to those in Group 2 and Group 3. COX-2 of Group 1 was
      significantly higher than the other groups. CONCLUSION: Ginkgo Biloba is helpful
      in the treatment of noise induced hearing loss and exerts its effect by
      inhibiting expression of IL-1 Beta, IL-6, TNF-alpha and COX-2 and increasing HSP
      70 and HSF-1 values in rat cochlea.

PMID- 29042072
TI  - miR-200b downregulates Kruppel Like Factor 2 (KLF2) during acute hypoxia in human
      endothelial cells.
AB  - The role of microRNAs in controlling angiogenesis is recognized as a promising
      therapeutic target in both cancer and cardiovascular disorders. However,
      understanding a miRNA's pleiotropic effects on angiogenesis is a limiting factor
      for these types of therapeutic approaches. Using genome-wide next-generation
      sequencing, we examined the role of an antiangiogenic miRNA, miR-200b, in primary
      human endothelial cells. The results indicate that miR-200b has complex effects
      on hypoxia-induced angiogenesis in human endothelia and importantly, that many of
      the reported miR-200b effects using miRNA overexpression may not be
      representative of the physiological role of this miRNA. We also identified the
      antiangiogenic KLF2 gene as a novel target of miR-200b. Our studies indicate that
      the physiological changes in miR-200b levels during acute hypoxia may actually
      have a proangiogenic effect through Klf2 downregulation and subsequent
      stabilization of HIF-1 signaling. Moreover, we provide a viable approach for
      differentiating direct from indirect miRNA effects in order to untangle the
      complexity of individual miRNA networks.

PMID- 29042073
TI  - Functional network dysconnectivity as a biomarker of treatment resistance in
      schizophrenia.
AB  - Schizophrenia may develop from disruptions in functional connectivity regulated
      by neurotransmitters such as dopamine and acetylcholine. The modulatory effects
      of these neurotransmitters might explain how antipsychotics attenuate symptoms of
      schizophrenia and account for the variable response to antipsychotics observed in
      clinical practice. Based on the putative mechanisms of antipsychotics and
      evidence of disrupted connectivity in schizophrenia, we hypothesised that
      functional network connectivity, as assessed using network-based statistics,
      would exhibit differences between treatment response subtypes of schizophrenia
      and healthy controls. Resting-state functional MRI data were obtained from 17
      healthy controls as well as individuals with schizophrenia who responded well to
      first-line atypical antipsychotics (first-line responders; FLR, n=18), had failed
      at least two trials of antipsychotics but responded to clozapine (treatment
      resistant schizophrenia; TRS, n=18), or failed at least two trials of
      antipsychotics and a trial of clozapine (ultra-treatment-resistant schizophrenia;
      UTRS, n=16). Data were pre-processed using the Advanced Normalization Toolkit and
      BrainWavelet Toolbox. Network connectivity was assessed using the Network-Based
      Statistics toolbox in Matlab. ANOVA revealed a significant difference in
      functional connectivity between groups that extended between cerebellar and
      parietal regions to the frontal cortex (p<0.05). Post-hoc t-tests revealed weaker
      network connectivity in individuals with UTRS compared with healthy controls but
      no other differences between groups. Results demonstrated distinct differences in
      functional connectivity between individuals with UTRS and healthy controls.
      Future work must determine whether these changes occur prior to the onset of
      treatment and if they can be used to predict resistance to antipsychotics during
      first-episode psychosis.

PMID- 29042074
TI  - Stereotactic vacuum-assisted breast biopsy: Comparison between 11- and 8-gauge
      needles.
AB  - PURPOSE: The 11-gauge (11G) stereotactic vacuum-assisted breast biopsy (VABB)
      showed a better profile than 14G-VABB in terms of feasibility, safety,
      microcalcification sampling, and accuracy. Underestimation rates were
      significantly lower with 11G-VABB than with 14G-VABB. Thus, the introduction of
      an even larger needle at the VABB procedure could reduce this rate further. The
      purpose of this study was to compare the overall performance of stereotactic VABB
      with 8G and 11G needles. MATERIALS AND METHODS: Four hundred and three VABBs
      performed between July 2012 and February 2015 at the Breast Diagnostic Unit of
      Careggi Hospital in Florence were retrospectively analyzed; 197 were performed
      with 11G-VABB and 206 with 8G-VABB. Lesions were classified according to
      mammographical patterns in microcalcifications, architectural distortions, or
      opacities, and all biopsy targets were classified according to BIRADS
      classification as BIRADS III, IV or V. Data were collected on radiological
      classification of targets, imaging presentation, procedure time, number of
      specimens per procedure, and microcalcification retrieval on histological
      findings. Surgery was always performed when high-risk or malignant lesions (B3 or
      B5) were detected; the final diagnosis was made on surgical pathology. RESULTS:
      Compared to VABB with an 11G needle, 8G-VABB allows a reduction in the time
      needed to complete the procedure (20.6 versus 27.4, P < 0.00001) and the number
      of specimens collected per lesion (21.6 versus 12.2, P < 0.00001). Moreover, 8G
      VABB resulted in the same diagnostic accuracy, and the underestimation rates were
      comparable between the two groups for both B3 and DCIS lesions. CONCLUSIONS: The
      8G needle should be considered as a valid alternative option in VABB for breast
      lesions.

PMID- 29042075
TI  - Evolution of type II endoleaks based on different ultrasound-identified patterns.
AB  - OBJECTIVE: The objective of this study was to delineate the specific types of
      waveforms that exist in type II endoleaks (T2ELs) and their effect on aneurysm
      sac size. METHODS: Patients who underwent an endovascular aneurysm repair and
      were diagnosed with a T2EL were included in the study. The flow velocity
      characteristics of the T2ELs were evaluated in detail with duplex ultrasound.
      Four different flow patterns were identified: high resistance, low flow; low
      resistance, low flow; low resistance, high flow; and to-fro flow. The type and
      number of vessels involved, time at detection, evolution, and need for treatment
      were recorded. The aneurysm sac diameter was monitored with duplex ultrasound. A
      computed tomography scan was always performed at baseline within 1 month of the
      procedure and repeated only when symptoms developed or there were changes in the
      ultrasound examination findings, such as sac enlargement. RESULTS: Of 382
      patients who underwent endovascular aneurysm repair in our institution, 56
      (14.65%) were found to have a T2EL. There were 52 male and four female patients
      with a mean age of 74 years (61-86 years). The T2EL was diagnosed within the
      first month in 32 patients; 9 patients were diagnosed at 3 months, 5 patients at
      6 months, 3 patients at 9 months, and 7 patients at 1 year or later. There were
      43 patients who had a T2EL involving one vessel; two vessels were involved in 11
      patients and three vessels were involved in two patients. During follow-up,
      several changes were observed for the different types of T2EL. High-resistance,
      low-flow endoleak was detected in 14 patients; of those, 13 were occluded and 1
      converted to high flow. Low-resistance, low-flow endoleak was detected in seven
      patients; of those, 5 were occluded, 1 remained stable, and 1 converted to high
      flow with sac enlargement requiring treatment. Low-resistance, high-flow endoleak
      was found in 13 patients; of those, 8 were occluded, 3 remained stable, and 2 had
      sac enlargement requiring treatment; 1 patient presented with rupture. Finally,
      to-fro flow was identified in the majority of the patients (22); of those, 14
      occluded, 3 remained stable, and 5 had sac enlargement requiring treatment; 2
      patients presented with rupture. No deaths due to T2EL were encountered.
      CONCLUSIONS: Most of the T2ELs resulted in spontaneous occlusion and were not
      associated with sac enlargement. A low-resistance, high-flow or to-fro flow T2EL
      has higher chances of sac enlargement, rupture, and requiring reintervention.

PMID- 29042077
TI  - Cross-countries migratory workers and tuberculosis: Lessons from Armenia.

PMID- 29042076
TI  - Perioperative outcomes after reoperative carotid endarterectomy are worse than
      expected.
AB  - OBJECTIVE: Reoperative carotid endarterectomy (CEA) can be technically
      challenging because of significant scarring as a consequence of the initial CEA
      procedure. There are limited data that describe outcomes after reoperative CEA,
      and as such, our goal was to determine the effect of reoperative CEA on
      perioperative outcomes. METHODS: The American College of Surgeons National
      Surgical Quality Improvement Program (ACS NSQIP) database was queried for
      patients undergoing index and reoperative CEA between 2005 and 2014. Multivariate
      analysis was performed to assess the effect of reoperative CEA on outcomes
      including stroke, major adverse cardiovascular event, and procedure time.
      RESULTS: There were 75,943 index and 140 reoperative CEAs identified. No
      differences were found in baseline demographics or comorbidities except that the
      reoperative group had a higher incidence of patients with end-stage renal disease
      (3.6% vs 1.1%; P = .004). Prior stroke with deficit (20.8% vs 15.4%; P = .137)
      and without deficit (11.5% vs 9.1%; P = .43) were similar between reoperative and
      index CEA groups. Both the reoperative and index initial CEA cohorts had
      comparable rates of surgical site infection (0.7% vs 0.3%; P = .462), return to
      the operating room (3.6% vs 4%; P = .816), readmission with 30 days (2.1% vs
      6.9%; P = .810), myocardial infarction (2.1% vs 0.9%; P = .125), and
      perioperative death (0.7% vs 0.9%; P = .853). The reoperative cohort had a
      significantly higher rate of perioperative stroke (5.0% vs 1.6%; P = .002) and a
      longer operative duration (137 +/- 54 vs 116 +/- 49 minutes; P < .001).
      Multivariate analysis revealed that reoperative CEA was an independent factor for
      postoperative stroke (odds ratio, 3.71; 95% confidence interval [CI], 1.61-8.57;
      P = .002), major adverse cardiovascular event (odds ratio, 2.76; 95% CI, 1.32
      5.78; P = .007), and longer procedure time (means ratio, 1.21; 95% CI, 1.12-1.30;
      P < .001). CONCLUSIONS: Reoperative carotid surgery is associated with a longer
      operative time and higher risk for perioperative stroke compared with index CEA.
      This information informs the risk-benefit analysis for reoperation.

PMID- 29042078
TI  - Bioactivity and fluoride release of strontium and fluoride modified Biodentine.
AB  - : BiodentineTM is a novel tricalcium silicate based material used both as a
      coronal dentine replacement and in pulp therapy. Its multiple use in sealing
      perforations, pulp capping and as a temporary restoration arises from its ability
      to promote dentine formation and to confer an excellent marginal seal. However,
      there is still room for improvement of this cement as it lacks the anticariogenic
      effect typically conferred by fluoride ion release as seen in glass ionomer
      cement based dental materials. Therefore, this study was conducted to investigate
      the impact of bioactive glass addition to BiodentineTM. OBJECTIVE: was to compare
      the apatite formation capacity, specificity of the apatite type formed and
      fluoride ion release by BiodentineTM cements that have been modified by three
      different compositions of bioactive glasses. METHODS: High fluoride, high
      strontium and high fluoride plus strontium containing bioactive glasses were
      synthesized, incorporated into BiodentineTM powder and four types of cements
      prepared. These cements were immersed in phosphate buffered saline solution and
      incubated for a period of 3 and 24h, 3, 7 and 14 days. Fourier transform infra
      red spectroscopy, X-ray diffraction, magic angle spinning nuclear magnetic
      resonance and fluoride ion release studies were performed. RESULTS: Bioactive
      glass addition to BiodentineTM led to pronounced formation of apatite. Where the
      bioactive glass contained fluoride, fluorapatite and fluoride ion release were
      demonstrated. SIGNIFICANCE: Eliciting fluorapatite formation and fluoride ion
      release from BiodentineTM is an important development as fluoride is known to
      have antibacterial and anticariogenic effects.

PMID- 29042079
TI  - Cytotoxicity and DNA double-strand breaks in human gingival fibroblasts exposed
      to eluates of dental composites.
AB  - OBJECTIVE: Previously, single composite components were used to study
      cytotoxicity and induction of DNA double-strand breaks (DNA-DSBs) of dental
      composite resins. In the present study, cytotoxicity and induction of DNA-DSBs in
      human gingival fibroblasts (HGFs) were investigated with dental composite eluates
      consisting of multiple components. The eluates were qualified and quantified.
      METHODS: The composites Esthet.X(r) HD, Venus(r), X-tra fil(r), CLEARFILTM AP-X,
      Admira(r) Fusion and QuiXfil(r) were polymerized and immersed into Dulbecco's
      modified Eagle's medium (DMEM) for 72h. Subsequently, HGFs were incubated with
      the corresponding composite eluates. The cell viability of HGFs was obtained from
      an XTT assay. DNA-DSBs were determined using a gamma-H2AX assay. The
      qualification and quantification of eluates were performed by gas
      chromatography/mass spectrometry (GC/MS). RESULTS: HGFs exposed to the eluates of
      all investigated composites showed no significant loss of cell viability,
      compared to negative control. Significant DNA-DSBs induction could be found in
      HGFs exposed to the eluates of Esthet.X(r) HD (0.43+/-0.05 foci/cell) and
      Venus(r) (0.39+/-0.04 foci/cell), compared to control (0.22+/-0.03 foci/cell). A
      total of 12 substances were detected from the investigated composite eluates.
      Five of them were methacrylates: tetraethyleneglycol dimethacrylate (TEGDMA), 2
      hydroxyethyl methacrylate (HEMA), hydroxypropyl methacrylate (HPMA),
      ethyleneglycol dimethacrylate (EGDMA) and trimethylolpropane trimethacrylate
      (TMPTMA). The highest concentration of HEMA (110.5MUM), HPMA (86.08MUM) and
      TMPTMA (4.50MUM) was detected in the eluates of QuiXfil(r). The highest
      concentration of TEGDMA was 1080MUM in Venus(r) eluates and the highest
      concentration of EGDMA was 3.18MUM in Esthet.X(r) HD eluates. SIGNIFICANCE:
      Significant DNA-DSBs induction can be found in HGFs exposed to the eluates of
      Esthet.X(r) HD and Venus(r). The interactive effects among released (co)monomers
      and additives may influence the cytotoxicity and induction of DNA-DSBs, compared
      to exposure with single composite component.

PMID- 29042080
TI  - APOL1 nephropathy risk variants do not associate with subclinical atherosclerosis
      or left ventricular mass in middle-aged black adults.
AB  - Prior studies reported associations of APOL1 nephropathy risk variants with
      subclinical atherosclerosis. However, these findings were limited to older
      individuals with high comorbidities. To evaluate this in younger individuals, we
      calculated associations of APOL1 risk variants (high risk [2 risk variants] vs.
      low risk [0-1 risk variant]) with prevalent, incident, or progressive coronary
      artery calcification, a carotid intima media thickness over the 90th percentile,
      and left ventricular hypertrophy in 1315 black participants of the Coronary
      Artery Risk Development in Young Adults (CARDIA) study. The mean age of this
      cohort was 44.6 years and their mean estimated glomerular filtration rate was
      102.5 ml/min/1.73m2. High-risk participants were found to be younger and have a
      higher prevalence of albuminuria than low-risk participants. In Poisson
      regression models adjusted for comorbidities and kidney function, the risk of
      prevalent coronary artery calcification (relative risk [95% confidence interval]
      1.12 [0.72,1.71]), the incident coronary artery calcification (1.50 [0.87,2.59]),
      and the progression of coronary artery calcification (1.40 [0.88,2.23]) did not
      significantly differ in high vs. low-risk participants. Furthermore, the risk of
      carotid intima media thickness over the 90th percentile (1.28 [0.78,2.10]) and
      left ventricular hypertrophy (1.02[0.73,1.43]) did not significantly differ in
      high vs. low-risk participants in fully-adjusted models. Thus, APOL1 risk
      variants did not associate with subclinical markers of atherosclerosis or left
      ventricular hypertrophy in middle-aged black adults with preserved kidney
      function.

PMID- 29042081
TI  - Peritoneal dialysis is associated with better cognitive function than
      hemodialysis over a one-year course.
AB  - Impaired cognitive functioning in patients with end-stage renal disease may
      reduce their capabilities to adhere to complex medical or dietary regimens and to
      fully participate in medical decisions. With decreasing renal function, cognitive
      abilities are likely to decline, with cognitive dysfunction improving after
      initiation of dialysis and even being generally reversible after successful renal
      transplantation. However, little is known about cognitive changes particularly
      regarding different treatment modalities. To gain further insight into this, we
      focused on a one-year course of cognitive functions, comparing peritoneal to
      hemodialysis patients. Within the CORETH-project, two validated neurocognitive
      tests, assessing executive functioning (Trail Making Test-B) and attention (d2
      Revision-Test) and the self-reported Kidney Disease Quality of Life Short Form
      Cognitive Function-subscale, were administered to 271 patients at baseline and
      after one year. Subsamples were matched by propensity score, adjusting for age,
      comorbidity, education, and employment status for 96 hemodialysis and 101
      peritoneal dialysis patients. The effects of time and treatment modality were
      investigated, controlling for well-known confounders. Both tests revealed
      improvement over one year. Peritoneal dialysis was associated with better
      outcomes than hemodialysis at baseline and follow-up, but comparability between
      groups may be limited. The opposite pattern applied to self-reporting.
      Hemodialysis patients had to be excluded from cognitive testing more often than
      peritoneal dialysis patients. As such, the number of exclusions may have biased
      the findings, limiting generalizability. Thus, our findings suggest an
      improvement of cognitive functioning and support previous indications for
      peritoneal dialysis being associated with better cognitive functions during a one
      year course than hemodialysis.

PMID- 29042082
TI  - The proto-oncogene tyrosine protein kinase Src is essential for macrophage
      myofibroblast transition during renal scarring.
AB  - Src activation has been associated with fibrogenesis after kidney injury.
      Macrophage-myofibroblast transition is a newly identified process to generate
      collagen-producing myofibroblasts locally in the kidney undergoing fibrosis in a
      TGF-beta/Smad3-dependent manner. The potential role of the macrophage
      myofibroblast transition in Src-mediated renal fibrosis is unknown. In studying
      this by RNA sequencing at single-cell resolution, we uncovered a unique Src
      centric regulatory gene network as a key underlying mechanism of macrophage
      myofibroblast transition. A total of 501 differentially expressed genes
      associated with macrophage-myofibroblast transition were identified. However,
      Smad3-knockout largely reduced the transcriptome diversity. More importantly,
      inhibition of Src largely suppresses ureteral obstruction-induced macrophage
      myofibroblast transition in the injured kidney in vivo along with transforming
      growth factor-beta1-induced elongated fibroblast-like morphology, alpha-smooth
      muscle actin expression and collagen production in bone marrow derived
      macrophages in vitro. Unexpectedly, we further uncovered that Src serves as a
      direct Smad3 target gene and also specifically up-regulated in macrophages during
      macrophage-myofibroblast transition. Thus, macrophage-myofibroblast transition
      contributes to Src-mediated tissue fibrosis. Hence, targeting Src may represent
      as a precision therapeutic strategy for macrophage-myofibroblast transition
      driven fibrotic diseases.

PMID- 29042083
TI  - Aprotinin prevents proteolytic epithelial sodium channel (ENaC) activation and
      volume retention in nephrotic syndrome.
AB  - Volume retention in nephrotic syndrome has been linked to activation of the
      epithelial sodium channel (ENaC) by proteolysis of its gamma-subunit following
      urinary excretion of serine proteases such as plasmin. Here we tested whether
      pharmacological inhibition of urinary serine protease activity might protect from
      ENaC activation and volume retention in nephrotic syndrome. Urine from both
      nephrotic mice (induced by doxorubicin injection) and nephrotic patients
      exhibited high aprotinin-sensitive serine protease activity. Treatment of
      nephrotic mice with the serine protease inhibitor aprotinin by means of
      subcutaneous sustained-release pellets normalized urinary serine protease
      activity and prevented sodium retention, as did treatment with the ENaC inhibitor
      amiloride. In the kidney cortex from nephrotic mice, immunofluorescence revealed
      increased apical gamma-ENaC staining, normalized by aprotinin treatment. In
      Xenopus laevis oocytes heterologously expressing murine ENaC, aprotinin had no
      direct inhibitory effect on channel activity but prevented proteolytic channel
      activation. Thus, our study shows that volume retention in experimental nephrotic
      syndrome is related to proteolytic ENaC activation by proteasuria and can be
      prevented by treatment with aprotinin. Hence, inhibition of urinary serine
      protease activity might become a therapeutic approach to treat patients with
      nephrotic-range proteinuria.

PMID- 29042084
TI  - Adenylyl cyclase 5 deficiency reduces renal cyclic AMP and cyst growth in an
      orthologous mouse model of polycystic kidney disease.
AB  - Cyclic AMP promotes cyst growth in polycystic kidney disease (PKD) by stimulating
      cell proliferation and fluid secretion. Previously, we showed that the primary
      cilium of renal epithelial cells contains a cAMP regulatory complex comprising
      adenylyl cyclases 5 and 6 (AC5/6), polycystin-2, A-kinase anchoring protein 150,
      protein kinase A, and phosphodiesterase 4C. In Kif3a mutant cells that lack
      primary cilia, the formation of this regulatory complex is disrupted and cAMP
      levels are increased. Inhibition of AC5 reduces cAMP levels in Kif3a mutant
      cells, suggesting that AC5 may mediate the increase in cAMP in PKD. Here, we
      examined the role of AC5 in an orthologous mouse model of PKD caused by kidney
      specific ablation of Pkd2. Knockdown of AC5 with siRNA attenuated the increase in
      cAMP levels in Pkd2-deficient renal epithelial cells. Levels of cAMP and AC5 mRNA
      transcripts were elevated in the kidneys of mice with collecting duct-specific
      ablation of Pkd2. Compared with Pkd2 single mutant mice, AC5/Pkd2 double mutant
      mice had less kidney enlargement, lower cyst index, reduced kidney injury, and
      improved kidney function. Importantly, cAMP levels and cAMP-dependent signaling
      were reduced in the kidneys of AC5/Pkd2 double mutant compared to the kidneys of
      Pkd2 single mutant mice. Additionally, we localized endogenous AC5 in the primary
      cilium of renal epithelial cells and showed that ablation of AC5 reduced ciliary
      elongation in the kidneys of Pkd2 mutant mice. Thus, AC5 contributes importantly
      to increased renal cAMP levels and cyst growth in Pkd2 mutant mice, and
      inhibition of AC5 may be beneficial in the treatment of PKD.

PMID- 29042086
TI  - Effects of heat and cadmium exposure on stress-related responses in the liver of
      female zebrafish: Heat increases cadmium toxicity.
AB  - In this study, female zebrafish (Danio rerio) were exposed to 26 degrees C or 34
      degrees C, 0 or 197MUg/L cadmium (Cd), singly or in combination for 7days.
      Multiple stress-related indicators were evaluated in the liver. Mortality, lipid
      peroxidation (LPO) and ultrastructural damage increased significantly by Cd
      exposure alone, and were not affected by heat alone. Interestingly, the combined
      exposure increased LPO, ultrastructural damage, and mortality compared with Cd
      exposure alone. The results indicated that elevated temperature increased Cd
      toxicity, which could be explained by several reasons. Firstly, Cd-exposed fish
      failed to activate the antioxidant defense system under heat stress. Secondly,
      expression levels of heat shock protein 70 (HSP70) were not significantly up
      regulated by heat in Cd-exposed fish but increased by 117 times in Cd-free fish.
      Besides, hypermethylation of heat shock factor (HSF) binding motif in HSP70
      promoter was observed during the combined exposure, indicating that simultaneous
      exposure may have partially suppressed the cytoprotective up-regulation of HSP70.
      Thirdly, heat induced an immunosuppressive effect in Cd-exposed fish, as
      reflected by the reduced mRNA and activity levels of nitric oxide synthase (iNOS)
      and interleukin-1beta (IL-1beta) expression levels. Finally, heat down-regulated
      Zir-, Irt-like protein 8 (ZIP8) and copper transporter 1 (CTR1) and up-regulated
      metallothioneins (MTs) in Cd-exposed fish, possibly suggesting Cu and Zn
      depletion and Cd accumulation. Hence, our data provide evidences that warmer
      temperatures can potentiate Cd toxicity, involved in the regulation of gene
      transcription, enzymatic activity, and DNA methylation. We found that heat
      indicators showed varied sensitivity between normal and Cd-exposed fish,
      emphasizing that the field metal pollution should be carefully considered when
      evaluating effects of climate change.

PMID- 29042085
TI  - Advances in the management of HER2-positive early breast cancer.
AB  - While trastuzumab is firmly established as the cornerstone of therapy for both
      early and advanced breast cancer expressing human epidermal growth factor
      receptor 2 (HER2), many patients either do not respond to trastuzumab treatment
      or progress following therapy. Improved understanding of breast cancer biology,
      particularly the complex signaling interactions managed by the HER family of
      receptors, have resulted in development of several novel HER2-directed therapies
      and combinations. This article will review the novel approaches to HER2 targeting
      that have been developed in recent years, with particular focus on results from
      these approaches in early breast cancer, and will discuss strategies to improve
      the tolerability of HER2-directed therapies, including prevention of cardiac
      toxicity and diarrhea.

PMID- 29042087
TI  - Methyl siloxanes in barbershops and residence indoor dust and the implication for
      human exposures.
AB  - Methyl siloxanes (MSs) have been widely added as emollients or solvents in
      various personal care products (PCPs) such as soap, shampoo and hair conditioner.
      A considerable percentage of MSs are released into the atmosphere directly from
      the use of PCPs in indoor environments. Indoor dust is a major reservoir of MSs,
      due to their particle-binding affinity. Dust ingestion could be one exposure
      pathway for special populations (hairdressers, for example). Though the toxicity
      of MSs is known, there is no information regarding the occurrence of MSs in
      barbershop dusts and the exposure of hairdressers through indoor dust ingestion.
      In the present study, the levels of three cyclic siloxanes (D4-D6) and 13 linear
      siloxanes (L4-L16) were measured in indoor dust samples collected from
      barbershops, and some other microenvironment including bathhouses, dormitories
      and households for comparison. The concentrations of ?MSs in barbershop dusts
      were one to two orders of magnitude higher than those from the other three indoor
      microenvironments. The daily intakes of ?MSs through indoor dust ingestion were
      estimated using the model of worst-case exposure (95th percentile concentration)
      and high dust ingestion, For the hairdressers in workplaces (barbershops), the
      exposure rates were 14.3ng/kg-bw/day, and for the general population, college
      students and toddlers (1-3yr), the corresponding exposure rates in living spaces
      were 3.43, 2.00 and 222ng/kg-bw/day, respectively. Such high exposure levels of
      MSs through dust ingestion indicate that we should not overlook the potential
      health risks for occupational groups and toddlers.

PMID- 29042088
TI  - Distribution of glyphosate and aminomethylphosphonic acid (AMPA) in agricultural
      topsoils of the European Union.
AB  - Approval for glyphosate-based herbicides in the European Union (EU) is under
      intense debate due to concern about their effects on the environment and human
      health. The occurrence of glyphosate residues in European water bodies is rather
      well documented whereas only few, fragmented and outdated information is
      available for European soils. We provide the first large-scale assessment of
      distribution (occurrence and concentrations) of glyphosate and its main
      metabolite aminomethylphosphonic acid (AMPA) in EU agricultural topsoils, and
      estimate their potential spreading by wind and water erosion. Glyphosate and/or
      AMPA were present in 45% of the topsoils collected, originating from eleven
      countries and six crop systems, with a maximum concentration of 2mgkg-1. Several
      glyphosate and AMPA hotspots were identified across the EU. Soil loss rates
      (obtained from recently derived European maps) were used to estimate the
      potential export of glyphosate and AMPA by wind and water erosion. The estimated
      exports, result of a conceptually simple model, clearly indicate that particulate
      transport can contribute to human and environmental exposure to herbicide
      residues. Residue threshold values in soils are urgently needed to define
      potential risks for soil health and off site effects related to export by wind
      and water erosion.

PMID- 29042089
TI  - Observation of nighttime new particle formation over the French Landes forest.
AB  - Improving the understanding of processes related to atmospheric particle sources
      is essential to better assess future climate. Especially, how biogenic volatile
      organic compounds (BVOCs) are involved in new particle formation (NPF) is still
      unclear, highlighting the need for field studies in sites that have not yet been
      explored. Weakly anthropised, mostly composed of maritime pines (known as strong
      monoterpene emitters), vast and under the influence of sea spray inputs, the
      Landes forest (located in the southwestern part of France) is a suitable
      ecosystem to explore these questions. The aim of the present work was to
      investigate for the first time NPF in the Landes forest, and to identify the
      conditions for NPF. During a field campaign conducted in July 2015, clear NPF was
      observed during nighttime, at a high frequency rate (37.5%), whereas only two
      daytime episodes were observed. Growth rates during NPF events were in the range
      9.0-15.7nmh-1, and nucleation rates (J10) in the range 0.8-8 particles cm3s-1,
      typically in the range of reported values from rural sites. Nocturnal NPF started
      at sunset, lagging the reductions of temperature and ozone concentration as well
      as the increase of relative humidity, atmospheric stability and monoterpene
      concentration. We established that NPF occurred during more stratified atmosphere
      episodes, reflecting that NPF is more influenced by local processes at the Landes
      forest site (Bilos). Concentration of the sum of monoterpenes, here mainly alpha-
      and beta-pinene, was observed to be maximal during NPF episodes. On the contrary,
      ozone concentration was lower, which may indicate a larger consumption during
      nights where NPF episodes occur. Results strongly suggest the contribution of
      BVOC oxidation to nocturnal NPF, in both nucleation and the growth stages.

PMID- 29042090
TI  - The natural history of flail chest injuries.
AB  - PURPOSE: Flail chest (FC) injuries represent a significant burden on trauma
      services because of its high morbidity and mortality. Current gold standard
      conservative management strategies for FC, are now being challenged by renewed
      interest in surgical rib fixation. This retrospective epidemiological study sets
      out to evaluate FC patients, and quantify the natural history of this injury by
      studying the injury patterns, epidemiology and mortality of patients sustaining
      FC injuries admitted to a major trauma centre (MTC). METHODS: A retrospective
      cohort analysis has been conducted at an MTC with full trauma service. All
      patients (age > 16 years) sustaining FC were included. Patient demographics,
      injury characteristics and inpatient stay information were extracted. RESULTS:
      Two hundred and ninety-three patients were identified, with a mean injury
      severity score (ISS) of 28.9 (range 9-75), average age of 56.1 years (range of 16
      100), and a male predominance (78%). Road traffic accidents accounted for 45% (n
      = 132) of injuries, whilst 44% were fall or jump from height (n = 129).
      Associated lung contusion was present in 133 patients (45%) while 76% of patients
      were found to have 5 or more ribs involved in the flail segment (n = 223) with
      96% (n = 281) having a unilateral FC. Inpatient treatment was required 19.9 days
      (range 0-150 days) with 59% of patients (n = 173) requiring intensive care unit
      (ICU) level care for 8.4 days (range 1-63) with 61.8% requiring mechanical
      ventilation (n = 107) for 10.5 days (range 1-54), and 7.8% underwent rib fixation
      with rib plates (n = 23). The mortality rate was found to be 14% (n = 42). A non
      significant trend towards improved outcomes in the conservative group was found
      when compared with the fixation group; ventilation days (6.94 vs 10.06, p = 0.18)
      intensive treatment unit (ITU) length of stay (LOS) (12.56 vs 15.53, p = 0.28)
      and hospital LOS (32.62 vs 35.24, p = 0.69). CONCLUSION: This study has
      successfully described the natural history of flail chest injuries, and has found
      a nonsignificant trend towards better outcomes with conservative management. With
      the cohort and management challenges now defined, work on outcome improvement can
      be targeted. In addition the comparability of results to other studies makes
      collaboration with other MTCs a realistic proposal.

PMID- 29042091
TI  - Effects of renal denervation on coronary flow reserve and forearm dilation
      capacity in patients with treatment-resistant hypertension. A randomized, double
      blinded, sham-controlled clinical trial.
AB  - BACKGROUND: Microvascular impairment is well documented in hypertension. We
      investigated the effect of renal sympathetic denervation (RDN) on cardiac and
      peripheral microvasculature in patients with treatment-resistant essential
      hypertension (TRH). METHODS: A randomized, single centre, double-blinded, sham
      controlled clinical trial. Fifty-eight patients with TRH (ambulatory systolic BP
      (ASBP) >= 145mmHg) despite stable treatment were randomized to RDN or SHAM. RDN
      was performed with the unipolar Medtronic Flex catheter. Coronary flow reserve
      (CFR) and coronary- and forearm minimum vascular resistance (C-Rmin and F-Rmin)
      were determined using transthoracic Doppler echocardiography and F-Rmin with
      venous occlusion plethysmography at baseline and at six-months follow-up.
      RESULTS: RDN was performed with 5.3+/-0.2 lesions in the right renal artery and
      5.4+/-0.2 lesions in the left. Baseline ASBP was 152+/-2mmHg (RDN, n=29) and
      154+/-2mmHg (SHAM, n=29). Similar reductions in MAP were seen at follow up (
      3.5+/-2.0 vs. -3.2+/-1.8, P=0.92). Baseline CFR was 2.9+/-0.1 (RDN) and 2.4+/-0.1
      (SHAM), with no significant change at follow-up (0.2+/-0.2 vs. -0.1+/-0.2,
      P=0.57). C-Rmin was 1.9+/-0.3 (RDN) and 2.7+/-0.6 (SHAM) (mmHgmin/ml pr. 100g)
      and did not change significantly (0.3+/-0.5 vs. -0.4+/-0.8, P=0.48). F-Rmin was
      3.6+/-0.2 (RDN) and 3.6+/-0.3 (SHAM) (mmHgmin/ml pr. 100ml tissue) and unchanged
      at follow-up (4.2+/-0.4 vs. 3.8+/-0.2, P=0.17). Left ventricular mass index was
      unchanged following RDN (-4+/-7 (RDN) vs. 3+/-5 (SHAM) (g/m2) P=0.38).
      CONCLUSION: The current study does not support positive effects of RDN on
      microvascular impairment in TRH.

PMID- 29042092
TI  - Quality of life after surgical treatment of coarctation in long-term follow-up
      (CoAFU): Predictive value of clinical variables.
AB  - BACKGROUND: We sought to analyze the quality of life and the predictive value of
      clinical variables from previous follow-up study in patients late after surgical
      treatment of aortic coarctation on the quality of life. METHODS: All patients,
      who have participated in the prospective cross-sectional COALA Study in 2000 with
      a structural clinical investigation including blood pressure measurement and
      symptom-limited exercise test were contacted for the health-related quality of
      life questionnaire SF-36 from January 2013 through December 2014. RESULTS: From
      273 eligible patients, we received data from 135 patients, 9 of them died during
      the follow-up time at the median age of 46years (range 30-64years). Seventy-four
      patients did not participate in the study, other 64 patients moved to remote or
      unknown areas and could not be contacted. Quality of life was good in the fields
      of physical role and pain. However, patients reported a significant impairment in
      general health and in health transition, depending on the age. Arterial
      hypertension and variables from echocardiography or exercise testing from the
      COALA study were not predictive on functional health status. CONCLUSION: Quality
      of life in patients late after aortic coarctation repair is fairly good compared
      with healthy controls. Impairments in general health and health transition depend
      mainly on age, can be explained due to numerous comorbidities and reinterventions
      in long-term. The predictive value of the commonly assessed clinical variables on
      quality of life is limited.

PMID- 29042093
TI  - Manifest ambiguity: Intermediate forms, variation, and mammal paleontology in
      Argentina, 1830-1880.
AB  - This paper presents the impact of diverse aspects of Darwin's works on the
      practices of mammal paleontology in different moments of nineteenth-century
      Argentina. Starting with Darwin through the publications of Florentino Ameghino,
      it shows the extraordinary complexity of systematic paleontology that
      characterized the second half of the nineteenth century. Neither "natural
      selection" nor "struggle for life" seemed to have shaped the practices of
      vertebrate paleontology in Argentina. Darwin's earlier work as a voyageur and
      geologist together with later concerns about intermediate forms and variation
      allow for an assessment of the impact of Darwin's work on the practice of
      paleontology in Argentina.

PMID- 29042094
TI  - Ustekinumab to treat Crohn's disease.
AB  - Ustekinumab is a monoclonal antibody directed against the p40 subunit, which is
      part of interleukins IL-12 and IL-23. The efficacy of ustekinumab versus placebo
      in terms of clinical response and remission of induction has been shown in phase3
      clinical trials. When used as subcutaneous maintenance therapy, the therapeutic
      benefit of ustekinumab over placebo has been confirmed in both clinical response
      and remission in patients who have responded clinically to induction therapy. In
      addition, ustekinumab has demonstrated an improvement in mucosal healing
      parameters. The safety profile of the drug has been good, with low infection
      rates (without reactivation of tuberculosis) and absence of tumour reporting. The
      development of drug immunogenicity appears to be rare. In summary, ustekinumab is
      a promising treatment option in patients with Crohn's disease, as an alternative
      to anti-TNFalpha drugs.

PMID- 29042096
TI  - A wolf in sheep's clothing.

PMID- 29042095
TI  - Can emergency physicians accurately distinguish retinal detachment from posterior
      vitreous detachment with point-of-care ocular ultrasound?
AB  - STUDY OBJECTIVE: There is significant overlap between the symptoms of patients
      presenting with retinal detachment (RD) and posterior vitreous detachment (PVD).
      Urgency to obtain consultation and treatment are dependent on the ability to
      accurately distinguish these two conditions. The objective of this study was to
      determine the ability of emergency physicians to differentiate RDs from PVDs
      using point-of-care (POC) ocular ultrasound. METHODS: Single blinded cross
      sectional study at an academic medical center. Emergency physicians with varying
      ultrasound experience completed a brief tutorial on the sonographic findings of
      RD and PVD. Thirty POC ocular ultrasound clips obtained from ED patients with
      ocular symptoms were presented to emergency physicians. The sonographic findings
      in these clips were in agreement with the final diagnosis made by consultant
      ophthalmologists. There were 14 ultrasound videos showing PVD, 13 videos showing
      RD, and 3 normal ocular ultrasound videos. The subjects independently reviewed
      POC ocular ultrasound video clips and submitted their final interpretations.
      RESULTS: A total of 390 ocular video clips were reviewed by 13 emergency
      physicians. Overall, physicians were able to accurately diagnose the presence of
      a RD 74.6% (95%CI, 69.8-79.4) of the time, PVD 85.7% (95%CI, 77.6-93.8) of the
      time, and normal ultrasounds 94.9% (95%CI 87.3-100.0) of the time. There was no
      statistically significant relationship between correct diagnoses for ocular
      abnormalities or normal ultrasound images and number of previous ocular
      ultrasounds performed by emergency physicians. CONCLUSION: Emergency physicians
      were modestly accurate in distinguishing RD from PVD on POC ultrasound.

PMID- 29042097
TI  - Routine preoperative thoracic angiography or just follow the gut feeling?

PMID- 29042098
TI  - The sum of small pieces.

PMID- 29042099
TI  - If your hospital has RATS, do not exterminate.

PMID- 29042100
TI  - Limited root repair in acute type A aortic dissection is safe but results in
      increased risk of reoperation.
AB  - OBJECTIVE: Management of the aortic root is a challenge for surgeons treating
      acute type A aortic dissection. METHODS: We performed a retrospective review of
      the acute type A aortic dissection experience at Stanford Hospital between 2005
      and 2015 and identified patients who underwent either limited root repair or
      aortic root replacement. Differences in baseline characteristics were balanced
      with inverse probability weighting to estimate the average treatment effect on
      the controls. Weighted logistic regression was used to evaluate in-hospital
      mortality. Weighted Cox proportional hazards regression was used to evaluate
      differences in the hazard for mid-term death. Reoperation was evaluated with
      death as a competing risk with the Fine-Gray subdistribution hazard. RESULTS:
      After we excluded patients managed either nonoperatively or with definitive
      endovascular repair, there were 293 patients without connective tissue disease
      who underwent either limited root repair or aortic root replacement. There was no
      difference in weighted perioperative mortality, odds ratio 0.89 (95% confidence
      interval [CI], 0.44-1.76, P = .7), and there was no difference in weighted
      survival, hazard ratio 1.12 (95% CI, 0.54-2.31, P = .8). Risk of reoperation was
      greater in limited root repair (11.8%, 95% CI, 0.0%-23.8%) than for root
      replacement (0%), P < .001. CONCLUSIONS: Limited root repair was associated with
      increased risk of late reoperation after repair of acute type A aortic
      dissection. Surgeons with adequate experience may consider aortic root
      replacement in well-selected patients. However, given good outcomes after limited
      root repair, surgeons should not feel compelled to perform this more-complex
      operation.

PMID- 29042101
TI  - Machine-learning phenotypic classification of bicuspid aortopathy.
AB  - BACKGROUND: Bicuspid aortic valves (BAV) are associated with incompletely
      characterized aortopathy. Our objectives were to identify distinct patterns of
      aortopathy using machine-learning methods and characterize their association with
      valve morphology and patient characteristics. METHODS: We analyzed preoperative 3
      dimensional computed tomography reconstructions for 656 patients with BAV
      undergoing ascending aorta surgery between January 2002 and January 2014.
      Unsupervised partitioning around medoids was used to cluster aortic dimensions.
      Group differences were identified using polytomous random forest analysis.
      RESULTS: Three distinct aneurysm phenotypes were identified: root (n = 83; 13%),
      with predominant dilatation at sinuses of Valsalva; ascending (n = 364; 55%),
      with supracoronary enlargement rarely extending past the brachiocephalic artery;
      and arch (n = 209; 32%), with aortic arch dilatation. The arch phenotype had the
      greatest association with right-noncoronary cusp fusion: 29%, versus 13% for
      ascending and 15% for root phenotypes (P < .0001). Severe valve regurgitation was
      most prevalent in root phenotype (57%), followed by ascending (34%) and arch
      phenotypes (25%; P < .0001). Aortic stenosis was most prevalent in arch phenotype
      (62%), followed by ascending (50%) and root phenotypes (28%; P < .0001). Patient
      age increased as the extent of aneurysm became more distal (root, 49 years;
      ascending, 53 years; arch, 57 years; P < .0001), and root phenotype was
      associated with greater male predominance compared with ascending and arch
      phenotypes (94%, 76%, and 70%, respectively; P < .0001). Phenotypes were visually
      recognizable with 94% accuracy. CONCLUSIONS: Three distinct phenotypes of
      bicuspid valve-associated aortopathy were identified using machine-learning
      methodology. Patient characteristics and valvular dysfunction vary by phenotype,
      suggesting that the location of aortic pathology may be related to the underlying
      pathophysiology of this disease.

PMID- 29042102
TI  - You can't always get what you want.

PMID- 29042103
TI  - Assembling the puzzle of polymorphism.

PMID- 29042104
TI  - Extending the perspective on left ventricular assist device pump thrombosis to
      left ventricular assist device system thrombosis.

PMID- 29042105
TI  - Total mercury flux and offshore transport via submarine groundwater discharge and
      coal-fired power plant in the Jiulong River estuary, China.
AB  - A mass balance of total mercury (HgT, dissolved+particulate) is constructed for
      China's Jiulong River estuary based on measured HgT concentrations in the surface
      water, sediment, porewater, and groundwater for May, August, and November 2009,
      combined with data from the literature. The HgT mass budget results show that the
      dominant source (39-55%) is desulfurized seawater discharged from the Songyu coal
      fired power plant. Submarine groundwater discharge (SGD)-derived HgT flux into
      the estuary is equivalent to 8-58% of the HgT input from the Jiulong River, which
      is remarkable when compared with SGD-derived HgT fluxes reported in coastal
      systems worldwide. Hence, SGD is a significant pathway for the transport of HgT
      into the Jiulong River estuary. The primary HgT sinks is export to the Taiwan
      Strait (53-88%), which has important environmental implications on the Hg cycling
      and marine ecosystems in marginal seas.

PMID- 29042106
TI  - Seasonal variability of picophytoplankton under contrasting environments in
      northern Tunisian coasts, southwestern Mediterranean Sea.
AB  - We investigated at the single cell level during 16months (June 2012 to September
      2013) the temporal distribution of picophytoplankton (picoeukaryotes,
      Synechococcus and Prochlorococcus) communities in two contrasted ecosystems: the
      Bay of Bizerte characterised by an oligotrophic regime typical of the
      Mediterranean Sea and the Bizerte Lagoon that exhibits a mesotrophic/eutrophic
      state. We aimed at depicting seasonal variations and quantifying the
      relationships between the environmental factors and the structure and abundance
      of picophytoplankton communities. Results showed that picophytoplankton groups
      were able to grow under a wide range of environmental conditions varying
      seasonally, although their abundances and contributions to the total chlorophyll
      biomass significantly varied and showed importance in the Bay of Bizerte.
      Synechococcus was the most abundant group reaching 225*103cells.cm-3 in the Bay
      and 278*103cells.cm-3 in the lagoon. This group was present all over the year in
      both ecosystems. Structural equation model results pointed out a different
      configuration regarding the picophytoplankton environmental drivers. The
      complexity of the configuration, i.e. number of significant links within the
      system, decreased under enhanced eutrophication conditions. The less exposure to
      anthropogenic stress, i.e. in the Bay of Bizerte, highlight a larger role of
      nutrient and hydrological conditions on the seasonal variations of
      picophytoplankton, whereas a negative effect of eutrophication on
      picophytoplankton communities was unveiled in the Bizerte Lagoon. We stress that
      such influence may be exacerbated under expected scenarios of Mediterranean
      warming conditions and nutrient release in coastal ecosystems.

PMID- 29042107
TI  - Amount, composition, and spatial distribution of floating macro litter along
      fixed trans-border transects in the Mediterranean basin.
AB  - Marine litter is a major source of pollution in the Mediterranean basin, but
      despite legislative requirements, scant information is available for the ongoing
      assessment of this threat. Using higher size classes as proxy for litter
      distribution, this study gave a synoptic estimation of the amount, composition,
      and distribution of floating macro-litter in the Mediterranean. The average
      amount of macro-litter was in a range of 2-5items/km2, with the highest in the
      Adriatic basin. Seasonal patterns were present in almost all study areas and were
      significant in the Ligurian Sea, Sardinian-Balearic basin, and Central Tyrrhenian
      Sea. Plastic accounted for >80% of litter in all areas and seasons, with the
      highest proportion in the Adriatic Sea, Ligurian Sea, and Sicilian-Sardinian
      Channels; in the Bonifacio Strait, Tyrrhenian Sea, and Sardinian-Balearic basin,
      litter composition was instead more diverse. Spatial analysis suggested an almost
      homogeneous distribution of litter without evident regular aggregation zones.

PMID- 29042108
TI  - Spatial distribution and environmental geochemistry of zinc metal in water and
      surficial bottom sediments of Lagoon Burullus, Egypt.
AB  - Lagoon Burullus is located in the North West quadrant of the Nile Delta. It
      receives drainage water through several drains around the lagoon. Understanding
      the mobility and bioavailability of zinc metal in bottom sediments of Lagoon
      Burullus is essential for the design of remediation processes and the institution
      of environmental recommendation for zinc pollution. Single extractions used to
      fractionate zinc into five fractions. The chemical analyses preceded using atomic
      absorption spectrometry after using the digestion technique. Zinc concentrates in
      the residual fraction (167.5MUg/g) followed by the organic (14.6MUg/g),
      exchangeable (3.2MUg/g), carbonate (2.4MUg/g) and then the Fe-Mn hydroxides
      (1MUg/g) fractions. The average content of zinc (189MUg/g) is about three fold
      the average earth's crust. Ecological pollution index show that the metal has a
      low-risk assessment to surrounding ecosystem. The anthropogenic activities
      considered as the main source of pollution.

PMID- 29042109
TI  - Construction of a scientific abstract.

PMID- 29042110
TI  - Measurement of thyroxine and its glucuronide in municipal wastewater and solids
      using weak anion exchange solid phase extraction and ultrahigh performance liquid
      chromatography-tandem mass spectrometry.
AB  - A solids extraction method, using sonication in combination with weak anion
      exchange solid phase extraction, was created to extract thyroxine (T4) and
      thyroxine-O-beta-d-glucuronide (T4-Glc) simultaneously from wastewaters and
      sludges, and to quantify these compounds via reversed-phase ultra-high
      performance liquid chromatography-tandem mass spectrometry. The method limits of
      quantification were all in the low ng/g (dry weight solids) range for both T4 and
      T4-Glc: 2.13 and 2.63ng/g respectively in primary wastewater, 4.3 and 28.3ng/g
      for primary suspended solids, for 1.1 and 3.7ng/g for return activated sludge.
      Precision for measurements of T4 and T4-Glc were 2.6 and 6.5% (intraday) and 9.6
      and 5.7% (interday) respectively, while linearity was 0.9967 and 0.9943
      respectively. Overall recoveries for T4 and T4-Glc in primary suspended solids
      were 94% and 95%, and 86 and 101% in primary wastewater, respectively. Extraction
      efficiency tests using primary sludge determined that one methanol aliquot was
      sufficient during the extraction process as opposed to 2 or 3 aliquots. Mass
      loadings at the North Main Wastewater Treatment Plant in Winnipeg, Canada showed
      316%, 714%, and 714% greater T4-Glc than T4 associated with the suspended solids
      of the primary, secondary, and final effluent respectively, yet 765% more T4 than
      T4-Glc associated with the solids of the mixed liquor. Moreover, 26% of T4 and
      49% of T4-Glc were associated with the suspended solids during the treatment
      process. This method demonstrates the need to assess accurately both metabolite
      conjugates of contaminants of emerging concern, as well as the sorbed levels of
      particle-reactive analytes such as T4 in the aquatic environment.

PMID- 29042111
TI  - Screening for 16-O-methylcafestol in roasted coffee by high-performance thin
      layer chromatography-fluorescence detection - Determination of Coffea canephora
      admixtures to Coffea arabica.
AB  - 16-O-Methylcafestol (16-OMC), the characteristic diterpene exclusively present in
      Coffea canephora, is an excellent marker for Coffea canephora admixtures to
      Coffea arabica. Here we show a straightforward, selective and sensitive screening
      method for the determination of 16-OMC in roasted coffee by high-performance thin
      layer chromatography with fluorescence detection (HPTLC-FLD). As internal
      standard, Sudan IV was used, and a direct saponification with 10% ethanolic
      potassium hydroxide solution was followed by solid supported liquid extraction
      with petroleum ether. 16-OMC was selectively derivatized with 2-naphthoyl
      chloride and analyzed by HPTLC-FLD on silica gel plates with cyclohexane/tert
      butyl methyl ether/formic acid (86:14:2, v/v/v) as the mobile phase. The enhanced
      fluorescence was scanned at UV 244/>320nm. Limits of detection and quantitation
      of 5 and 14mg 16-OMC/kg coffee allowed the determination of Coffea canephora
      admixtures to Coffea arabica below 1%. Recoveries for blends of Coffea arabica
      with Coffea canephora were close to 100%.

PMID- 29042112
TI  - Micro-solid phase extraction of benzene, toluene, ethylbenzene and xylenes from
      aqueous solutions using water-insoluble beta-cyclodextrin polymer as sorbent.
AB  - Water-insoluble beta-cyclodextrin polymer was synthesized by chemical cross
      linking using epichlorohydrin (EPI) as a cross-linker agent. The produced water
      insoluble polymer was used as a sorbent for the micro-solid phase extraction (MU
      SPE) of benzene, toluene, ethylbenzene and xylenes (BTEX) from water samples. The
      MU-SPE device consisted of a sealed tea bag envelope containing 15mg of sorbent.
      For the evaluation of the extraction efficiency, parameters such as extraction
      and desorption time, desorption solvent and salt concentration were investigated.
      At an extraction time of 30min in the course of the extraction process, analytes
      were extracted from a 10mL aqueous sample solution. The analytes were desorbed by
      ultrasonication in 200MUL of acetonitrile for 20min. Analysis of the analytes was
      done by a gas chromatography-flame ionization detector (GC-FID) system. The
      enrichment factor (EF) was found to be in the range 23.0-45.4 (EFmax=50.0). The
      method provided linearity ranges of between 0.5 and 500.0ng/mL (depending on the
      analytes), with good coefficients of determination (r2) ranging between 0.997 and
      0.999 under optimized conditions. Detection limits for BTEX were in the range of
      between 0.15 and 0.60ng/mL, while corresponding recoveries were in the range of
      46.0-90.0%. The relative standard deviation of the method for the analytes at
      100.0ng/mL concentration level ranged from 5.5 to 11.2% (n=5). The proposed
      method was concluded to be a cost effective and environmentally-friendly
      extraction technique with ease of operation and minimal usage of organic solvent.

PMID- 29042113
TI  - Extension of Golay plate height equation for open-tubular columns.
AB  - Golay plate height equation with its B-term equal to 2Dm/u (Dm is molecular
      diffusivity of a solute in the carrier gas and u is the gas velocity) has been
      developed for WCOT (wall-coated open-tubular) GC columns with liquid stationary
      phases. In a more general case of OTC (open tubular columns) such as the PLOT
      (porous layer open-tubular) columns and others, the B-term is 2(Dm+kDS)/u (DS and
      k are the solute net diffusivity in the stationary zone and the retention factor,
      respectively) which can be substantially larger than 2Dm/u. A simple proof is
      provided together with other adjustments in Golay equation, and its
      interpretation.

PMID- 29042114
TI  - Extending the service life of existing dental restorations with esthetic and
      functional limitations.
AB  - Adhesive cementation is a useful procedure not only for cementing restorations
      onto teeth but also for attaching new ceramic restorations to existing
      restorations to improve their esthetics and/or function. This clinical report
      presents a technique for modifying an existing nonsatisfactory implant-supported
      fixed dental prosthesis by means of adhesively cemented veneers and onlays bonded
      to the pre-existing metal-ceramic surface with resin cement. This modification
      may avoid the replacement of the fixed dental prosthesis, reducing both treatment
      costs and time while fulfilling the patient's demands.

PMID- 29042115
TI  - Effect of thickness and surface modifications on flexural strength of monolithic
      zirconia.
AB  - STATEMENT OF PROBLEM: A recommended minimum thickness for monolithic zirconia
      restorations has not been reported. Assessing a proper thickness that has the
      necessary load-bearing capacity but also conserves dental hard tissues is
      essential. PURPOSE: The purpose of this in vitro study was to evaluate the effect
      of thickness and surface modifications on monolithic zirconia after simulated
      masticatory stresses. MATERIAL AND METHODS: Monolithic zirconia disks (10 mm in
      diameter) were fabricated with 1.3 mm and 0.8 mm thicknesses. For each thickness,
      21 disks were fabricated. The specimens of each group were further divided into 3
      subgroups (n=7) according to the surface treatments applied: untreated (control),
      airborne-particle abrasion with 50-MUm Al2O3 particles at a pressure of 400 kPa
      at 10 mm, and grinding with a diamond rotary instrument followed by polishing.
      The biaxial flexure strength was determined by using a piston-on-3-balls
      technique in a universal testing machine. Flexural loading was applied with a 1.4
      mm diameter steel cylinder, centered on the disk, at a crosshead speed of 0.5
      mm/min until fracture occurred. X-ray diffraction (XRD) and scanning electron
      microscopy (SEM) analyses were performed. The data were statistically analyzed
      with 2-way ANOVA, Tamhane T2, 1-way ANOVA, and Student t tests (alpha=.05).
      RESULTS: The 1.3-mm specimens had significantly higher flexural strength than the
      0.8-mm specimens (P<.05). Airborne-particle abrasion significantly increased the
      flexural strength (P<.05). Grinding and polishing did not affect the flexural
      strength of the specimens (P>.05). CONCLUSIONS: The mean flexural strength of 0.8
      mm and 1.3-mm thick monolithic zirconia was greater than reported masticatory
      forces. Airborne-particle abrasion increased the flexural strength of monolithic
      zirconia. Grinding did not affect flexural strength if subsequently polished.

PMID- 29042116
TI  - Marginal discrepancy dimensions of single unit metal crowns fabricated by using
      CAD-CAM-milled acrylate resin polymer blocks or a conventional waxing technique.
AB  - STATEMENT OF PROBLEM: Because crowns with open margins are a well-known problem
      and can lead to complications, it is important to assess the accuracy of margins
      resulting from the use of a new technique. Currently, data regarding the marginal
      fit of computer-aided design and computer-aided manufacturing (CAD-CAM)
      technology to fabricate a complete gold crown (CGC) from a castable acrylate
      resin polymer block are lacking. PURPOSE: The purpose of this in vitro study was
      to compare marginal discrepancy widths of CGCs fabricated by using either
      conventional hand waxing or acrylate resin polymer blocks generated by using CAD
      CAM technology. MATERIAL AND METHODS: A plastic model of a first mandibular molar
      was prepared by using a 1-mm, rounded chamfer margin on the entire circumference
      of the tooth. The master die was duplicated 30 times, and 15 wax patterns were
      fabricated by using a manual waxing technique, and 15 were fabricated by using
      CAD-CAM technology. All patterns were invested and cast, and resulting CGCs were
      cemented on their respective die by using resin-modified glass ionomer cement.
      The specimens were then embedded in acrylic resin and sectioned buccolingually.
      The buccal and lingual marginal discrepancies of each sectioned portion were
      measured by using microscopy at *50 magnification. Data were subjected to
      repeated measures 2-way ANOVA, by using the Tukey post hoc pairwise comparison
      test (alpha=.05). RESULTS: The factor of "technique" had no significant influence
      on marginal discrepancy measurement (P=.431), but a significant effect of "margin
      location" (P=.019) was noted. The confounding combination of factors was found to
      be significantly lower marginal discrepancy dimensions of the lingual margin
      discrepancy than on the buccal side by using CAD-CAM technology. CONCLUSIONS: The
      marginal discrepancy of CAD-CAM acrylate resin crowns was not significantly
      different from those made with a conventional manual method; however, lingual
      margin discrepancies present from CAD-CAM-prepared crowns were significantly less
      than those measured on the respective buccal surface.

PMID- 29042117
TI  - Restoring masticatory function in a patient with severe microstomia using rapid
      prototyped mesh and a custom-made hinge and swing-lock prosthesis.
AB  - This clinical report describes the use of rapid prototyped mesh in a complete
      swing-lock prosthesis to restore masticatory function in an edentulous patient
      with severe microstomia and perioral scar tissue after an industrial hot tar
      accident.

PMID- 29042118
TI  - The early development of the normative mind.
AB  - Normativity is pervasive in everyday human social interactions and perhaps even
      constitutive of human forms of group and societal living. During the past decade,
      there has been increased interest in the ontogeny of normativity and the role
      that norms play in early social reasoning and behavior. Given the ubiquity of
      normativity, it is vital to investigate the development of children's normative
      understanding and behavior in a variety of different contexts, ranging from
      prosocial behavior to rational action or from linguistic competencies to cultural
      norms and values. Hence, in this special issue on the early development of the
      normative mind, researchers from different theoretical traditions have employed a
      number of different methods (e.g., third-party norm enforcement, judgment and
      reasoning, social behavior) to address different, yet related, research questions
      about the ontogeny of normativity. Here, we introduce the reader to the current
      debate and point to important research questions for the field.

PMID- 29042119
TI  - Walking Forward: A narrative from South Dakota.

PMID- 29042120
TI  - Pilot study on the impact of F18-labeled thymidine PET/CT on gross tumor volume
      identification and definition for pancreatic cancer.
AB  - PURPOSE: Accurate target definition for radiation therapy planning in localized
      pancreatic cancer is critical, particularly when using strategies that omit
      elective coverage. Standard imaging modalities such as computed tomography (CT),
      magnetic resonance imaging, and endoscopic ultrasound have limited concordance
      with pathologic evaluation. Biologic imaging with [F18]-fluorodeoxyglucose (FDG)
      positron emission tomography (PET) can also be difficult to interpret because
      increased activity is indicative of increased glucose metabolism, rather than
      cellular proliferation. [F18]-3'-deoxy-3'-fluorothymidine labeled thymidine (FLT)
      is a proliferative marker which exploits the expression of pyrimidine
      metabolizing enzymes. We evaluate the impact of FLT-PET on pancreatic target
      definition for radiation planning. METHODS AND MATERIALS: Patients with biopsy
      proven, newly diagnosed, untreated pancreatic adenocarcinoma were enrolled on an
      institutional review board-approved prospective study. Patients were injected
      with FLT and scanned 20 to 30 minutes later. Two physicians (referred to as
      observer 1 and observer 2) independently contoured the gross tumor volume (GTV)
      and involved nodes on CT scan only and then again with the assistance of
      coregistered FLT-PET. Conformality index (CI), the ratio of the volumes of
      intersection and union, was used as the metric for volume comparison (where CI =
      0 represents no overlap and CI = 1 represents perfect overlap). RESULTS: Nine
      patients were enrolled in this study. FLT-avidity was discerned in 8 of 9
      patients. Average CT-GTV volume for observers 1 and 2 was 38.1 and 26.5 mL,
      respectively. Average FLT-GTV volume for observers 1 and 2 was 39.1 and 25.0 mL,
      respectively. For the 8 patients with FLT-avid tumors, addition of FLT data
      improved concordance of GTV definition between physicians in 6 of 8 tumors.
      Average CI for interobserver CT-GTV was 0.325. Addition of FLT-PET information
      improved the average CI to 0.400. CONCLUSIONS: FLT-PET improves interobserver
      concordance in GTV definition. Further studies will focus on verification of
      these findings, pathologic verification of the FLT-PET signal, and optimization
      of the FLT-PET signal threshold for autosegmentation.

PMID- 29042121
TI  - Auditory sequential accumulation of spectral information.
AB  - In many listening situations, information about the spectral content of a target
      sound may be distributed over time, and estimating the target spectrum requires
      efficient sequential processing. Listeners' ability to estimate the spectrum of a
      random-frequency, six-tone complex was investigated and the spectral content of
      the complex was revealed using a sequence of bursts. Whether each of the six
      tones was presented within each burst was determined at random according to a
      presentation probability. In separate conditions, the presentation probabilities
      (p) ranged from 0.2 to 1, the total number of bursts varied from 1 to 16, and the
      inter-burst interval was either 0 or 200 ms. To evaluate the information acquired
      by the listener, the burst sequence was followed, after a 500-ms silent interval,
      by the six-tone complex acting as an informational masker and the listener was
      required to detect a pure-tone target presented simultaneously with the masker.
      Greater performance in this task indicates more accurate estimation of the
      spectrum of the complex by the listener. Evidence for integration of information
      across bursts was observed, and the integration process did not significantly
      depend on inter-burst interval.

PMID- 29042122
TI  - Physical activity after coronary revascularization.

PMID- 29042123
TI  - Wise decisions, good results.

PMID- 29042124
TI  - Cardiac biomarkers: on the track of reverse remodeling?

PMID- 29042126
TI  - Re: Magnetic Resonance Imaging Underestimation of Prostate Cancer Geometry: Use
      of Patient-specific Molds to Correlate Images with Whole-mount Pathology.

PMID- 29042125
TI  - Survival Outcomes of Men with Lymph Node-positive Prostate Cancer After Radical
      Prostatectomy: A Comparative Analysis of Different Postoperative Management
      Strategies.
AB  - BACKGROUND: Optimal management of patients with lymph node metastasis (LNM) after
      radical prostatectomy (RP) remains undefined. OBJECTIVE: We evaluated the
      association between three different management strategies and survival in
      prostate cancer with LNM after RP. DESIGN, SETTING, AND PARTICIPANTS: We analyzed
      data of 1338 patients with LNM after RP from three tertiary care centers. Three
      hundred and eighty-seven patients (28%) were observed, 676 (49%) received
      lifelong adjuvant androgen deprivation therapy (ADT), and 325 (23%) received
      adjuvant external beam radiation therapy (EBRT) and ADT. Three hundred and sixty
      eight men were followed for more than 10 yr. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Primary outcome measure was overall survival (OS). Secondary outcomes
      were cancer-specific survival (CSS) and other-cause mortality. Kaplan-Meier
      methods were used to visualize OS for the three treatment groups. Cox
      proportional hazards regression was utilized to compare OS and CSS among the
      three groups. RESULTS AND LIMITATIONS: ADT+EBRT was associated with better OS
      than ADT alone (hazard ratio [HR]: 0.46, 95% confidence interval [CI]: 0.32-0.66,
      p<0.0001) or observation (HR: 0.41, 95% CI: 0.27-0.64, p<0.0001). Higher-risk
      patients benefited more from ADT+EBRT than lower-risk patients. Ten-year
      mortality risk difference between ADT+EBRT, observation, or ADT alone ranged from
      5% in low-risk patients to 40% in high-risk patients. Adjuvant ADT+EBRT was also
      associated with better CSS than observation or ADT alone (p<0.0001), ADT had
      better CSS compared to observation (HR: 0.64, 95% CI: 0.43-0.95, p=0.027).
      However, ADT was associated with an increased risk of other-cause mortality (HR:
      3.05, 95% CI: 1.45-6.40, p=0.003) compared with observation, resulting in similar
      OS between ADT and observation (HR: 0.90, 95% CI: 0.65-1.25, p=0.5). While
      selection bias might remain, its effect would operate in the opposite direction
      to our findings. CONCLUSIONS: In men with LNM after RP, ADT+EBRT improved
      survival over either observation or adjuvant ADT alone. This survival benefit
      increases with higher-risk disease. PATIENT SUMMARY: Lymph node metastasis
      following radical prostatectomy is associated with poor survival outcomes.
      However, we found that adjuvant androgen deprivation therapy with external beam
      radiation therapy improved survival in these patients.

PMID- 29042127
TI  - Pinitol alleviates systemic inflammatory cytokines in human obesity by a
      mechanism involving unfolded protein response and sirtuin 1.
AB  - BACKGROUND & AIMS: It is known that pinitol acts as a mediator of the insulin
      signaling pathway, though little is known about its anti-inflammatory effect in
      human obesity. Therefore, this study aimed to evaluate the effect of pinitol on
      peripheral blood mononuclear cells (PBMCs) and visceral (VAT) and subcutaneous
      adipose tissues (SAT), focusing on the involvement of endoplasmic reticulum (ER)
      stress and sirtuin 1 (SIRT1). METHODS: In the intervention study, thirteen obese
      subjects consumed a pinitol-enriched beverage (PEB) for 12 weeks. In the ex vivo
      study, a biopsy of VAT and SAT was removed from thirty-four obese patients and
      incubated with D-pinitol for 48 h. RESULTS: The consumption of a PEB reduced
      circulating levels of IL6 and TNFalpha and increased SIRT1 protein expression in
      PBMCs. Ex vivo experiments showed a decline in gene expression and protein levels
      of IL6 and TNFalpha in SAT and a reduction in ER stress parameters (ATF6 and
      CHOP), while VAT markers remained unaltered. Differential gene expression
      profiles revealed an up-regulation of SIRT1 and insulin-signaling pathways in SAT
      with respect to VAT. CONCLUSIONS: Our results suggests that pinitol down
      regulates the inflammatory pathway which may lead to novel treatment options for
      obesity and its metabolic disorders.

PMID- 29042129
TI  - Epigenetic Pathways Offer Targets for Ovarian Cancer Treatment.

PMID- 29042128
TI  - Impact of blood pressure, cholesterol and glucose in the association between
      adiposity measures and coronary heart disease and stroke among Iranian
      population.
AB  - BACKGROUND & AIMS: To determine the association of body mass index (BMI) and
      central adiposity measures with coronary heart disease (CHD)/stroke, and to
      quantify the impact of blood pressure, cholesterol and glucose as metabolic
      mediators on these associations. METHODS: The study population included 4631
      Iranian participants (males = 2066) aged >=40 years. Cox proportional hazard
      model was used to estimate the hazard ratio (HR) of BMI and central adiposity
      measures, using continuous and categorical variables, on CHD/stroke, with and
      without adjustment for three metabolic mediators, to calculate the attenuation of
      excess risk after adjustment for mediators. RESULTS: During a median follow-up of
      12.1 years, 606 and 132 subjects experienced incident CHD and stroke,
      respectively. In the sex and confounders adjusted model, overweight and obesity
      were associated with increased risk for CHD (HR: 1.56; 95% CI: 1.26-1.92) and
      [1.53 (1.21-1.94)], respectively; however, after further adjustment for all the
      mediators, the result was significant only for overweight status [1.29 (1.05
      1.59)]. Considering stroke, a significant risk of 70% (1.05-2.72) was found only
      among obese population. The percentage of risk mediated by three mediators among
      obese population was 75.47% and 75.71% for CHD and stroke, respectively. Blood
      pressure was the most important mediator of obesity, accounting for at least 50%
      of the excess risk for CHD and 60% for stroke. Considering central obesity
      measures, in the presences of all mediators, a significant risk for CHD was
      demonstrated; regarding stroke events, the risk was marginally significant for
      waist to height [1.02 (0.99-1.05)] and waist to hip ratios [1.02 (1.00-1.05)].
      CONCLUSIONS: Overweight and obesity for CHD and, obesity for stroke were
      associated with increased risk; the negative effect of obesity was potentially
      ameloriated about 70% after adjustment for mediators. However, overweight status
      and central adiposity highlighted significant risk that did not decrease after
      controlling for traditional risk factors.

PMID- 29042130
TI  - A decay of the adaptive capacity of the unfolded protein response exacerbates
      Alzheimer's disease.
AB  - Alterations in the buffering capacity of the proteostasis network are a salient
      feature of Alzheimer's disease, associated with the occurrence of chronic
      endoplasmic reticulum (ER) stress. To cope with ER stress, cells activate the
      unfolded protein response (UPR), a signal transduction pathway that enforces
      adaptive programs through the induction of transcription factors such as X-box
      binding protein 1 (XBP1). A new study by Marcora et al used a fly model to study
      amyloid beta pathogenesis in the secretory pathway of neurons. Through genetic
      manipulation, authors identified a new role of XBP1s in the clearance of amyloid
      beta and the improvement of neuronal function. However, although the activation
      of the UPR signaling was sustained over time, the transcriptional upregulation of
      XBP1-target genes was attenuated during aging. This study suggests that aging has
      a negative impact in the ability of the UPR to manage proteostasis alterations in
      Alzheimer's disease.

PMID- 29042131
TI  - Expanding our perspectives on research in musculoskeletal science and practice.
AB  - INTRODUCTION: The quantity and quality of scientific research within
      physiotherapy has unquestionably grown and matured over the last few decades,
      especially since the "formal" onset of evidence-based physiotherapy in the 1990s.
      The urgent need to evaluate our practice for effectiveness and efficiency has
      been responded to with thought and respect to both scientific integrity and shop
      floor clinical needs. However, after thirty years or more of a professionally
      governed and strategic approach to research activity, it is now timely to
      reflect, review, and consider the next chapter in the relationship between
      scientific research and clinical practice. PURPOSE: This masterclass aims to
      develop a research vision for the future of physiotherapy. It is proposed that a
      crisis is evident within evidence-based physiotherapy, particular so given the
      assumed complexity and context-sensitivity of our clinical practice. This crisis
      period has highlighted fundamental limitations within the way research and
      practice are currently related. These limitations are presented and framed within
      the problematisation of empirical and philosophical concerns. As research becomes
      increasingly aligned to traditional scientific principles, examination of the
      real world context in which its outcomes are intended expose critical challenges
      for both research and clinical practice. IMPLICATIONS: A reconceptualisation of
      fundamental elements of scientific research may allow more meaningful
      relationships between research and clinical practice. A proposed research vision
      encourages scientific activity to embrace real-world complexity in a way that it
      is presently unable to. An enhanced person-centered, scientifically-informed
      world of effective musculoskeletal practice is envisaged.

PMID- 29042133
TI  - Determination of mitochondrial metabolic phenotype through investigation of the
      intrinsic inhibition of succinate dehydrogenase.
AB  - Many diseases are accompanied by systemic or organ metabolic abnormalities.
      Therefore, investigation of the roles of mitochondrial dysfunction in the
      pathogenesis of major diseases requires a methodology that reflects the
      characteristics of mitochondrial metabolism particular for the organ of origin.
      We provide evidence that for brain and heart mitochondria the intrinsic
      inhibition of succinate dehydrogenase (SDH) is a key mechanism for attenuation of
      mitochondrial respiration and energy production in response to the organ's energy
      needs. This mechanism also serves to minimize the production of reactive oxygen
      species when the organ is at rest. Changes in the organ's workloads are
      accompanied by changes in metabolites that are used by mitochondria as substrates
      and for modification of energy production at the SDH level. Measurement of the
      respiratory activity of mitochondria with various substrates and substrate
      mixtures and use of bovine serum albumin as an SDH inhibitor will be useful for
      evaluation of metabolic phenotype at the mitochondrial level.

PMID- 29042132
TI  - Low Very low-Density Lipoprotein Cholesterol but High Very low-Density
      Lipoprotein Receptor mRNA Expression in Peripheral White Blood Cells: An
      Atherogenic Phenotype for Atherosclerosis in a Community-Based Population.
AB  - Very low-density lipoprotein cholesterol (VLDL-C), via binding very low-density
      lipoprotein receptor (VLDLR), can induce the development of atherosclerosis.
      Besides monocytes, VLDLR expression is detected in various peripheral white blood
      cells (WBCs), yet its underlying role remains unclear. We thereby aimed to test
      the hypothesis that VLDLR in all types of peripheral WBCs may be involved in the
      association between VLDL-C and atherosclerosis. VLDLR mRNA expression in
      peripheral WBC and plasma VLDL-C levels were measured in 747 participants from a
      community-based study. Plaque prevalence and total plaque area (TPA) were used to
      evaluate the burden of carotid atherosclerosis. VLDL-C was positively associated
      with atherosclerosis risk, whereas this association was modified by VLDLR mRNA
      level. In participants with the lowest VLDL-C but the highest VLDLR mRNA
      expression, the risk for plaque prevalence unexpectedly was the highest. This
      association was also observed for TPA. Moreover, this association remained
      unchanged after adjusting for WBC or monocytes. Our findings described an
      atherogenic phenotype characterized by low VLDL-C but high VLDLR mRNA expression
      in peripheral WBCs, which suggested that VLDLR in all types of peripheral WBCs
      may be involved in lipid deposition, and VLDL-C and VLDLR may co-determine the
      development of atherosclerosis.

PMID- 29042134
TI  - The use of dynamic radiographs in trapeziometacarpal joint arthrodesis for
      accurate range of motion evaluation.
AB  - BACKGROUND: Increased motion at the scaphotrapeziotrapezoidal (STT) joint and
      compensatory hypermobility of metacarpophalangeal (MP) joint contribute to the
      total abduction and adduction motion of the thumb after trapeziometacarpal (TM)
      joint arthrodesis. However, there were no detailed studies to evaluate the
      contribution of motion of each joint towards total thumb mobility. METHODS: We
      conducted a comparative study on thumb joint motion in 56 hands who underwent TM
      joint arthrodesis against that of 56 hands in normal subjects. Dynamic
      radiographs were performed and the angles subtended by the first (M1) and second
      (M2) metacarpals were to measure radial abduction and adduction, and volar
      abduction and adduction. In addition, angles subtended by the thumb proximal
      phalanx (P1) and M1 in abduction and adduction were measured to evaluate the
      hypermobility of the MP joint. RESULTS: The average total arcs of M1M2 motion in
      normal subjects in radial and volar abduction-adduction planes were 24 degrees 
      and 35 degrees  respectively. The arthrodesis group averaged 9 degrees  of motion
      in the radial abduction and adduction plane and 8 degrees  in the volar abduction
      and adduction plane. P1M1 volar adduction angle was significantly larger in the
      arthrodesis group, suggesting that the arthrodesis group had larger compensatory
      motion of the MP joint in volar adduction compared to normal subjects.
      CONCLUSIONS: These findings on the amount of hypermobility of MP joint after TM
      joint arthrodesis are valuable information for optimal postoperative
      rehabilitation protocol. To achieve good range of motion of thumb abduction and
      adduction following TM joint arthrodesis, emphasis must be placed in obtaining
      maximum potential motion of STT joint rather than hypermobility of MP joint.

PMID- 29042135
TI  - Linkages between the spatial toxicity of sediments and sediment dynamics in the
      Yangtze River Estuary and neighboring East China Sea.
AB  - Anthropogenic activities are driving an increase in sediment contamination in
      coastal areas. This poses significant challenges for the management of estuarine
      ecosystems and their adjacent seas worldwide. However, few studies have been
      conducted on how dynamic mechanisms affect the sediment toxicity in the estuarine
      environment. This study was designed to investigate the linkages between sediment
      toxicity and hydrodynamics in the Yangtze River Estuary (YRE) area. High sediment
      toxicity was found in the Yangtze River mouth (Region I), the depocenter of the
      Yangtze River Delta (Region II), and the southeastern area of the adjacent sea
      (Region III), while low sediment toxicity was found in the northeastern offshore
      region (Region IV). A spatial comparison analysis and regression model indicated
      that the distributed pattern of sediment toxicity was likely related to
      hydrodynamics and circumfluence in the East China Sea (ECS) shelf. Specifically,
      high sediment toxicity in Region I may be affected by the Yangtze River Pump
      (YRP) and the low hydrodynamics there, and high toxicity in Region II can be
      influenced by the low sediment dynamics and fine sediment in the depocenter. The
      high sediment toxicity in Region III might be related to the combination of the
      YRP and Taiwan Warm Current, while the low toxicity in Region IV may be
      influenced by the local coarse-grained relict sand with strong sediment dynamics
      there. The present research results further suggest that it is necessary to link
      hydrodynamics and the spatial behavior of sediment and sediment-derived
      pollutants when assessing the pollution status of estuarine environments,
      especially for those mega-estuaries and their neighboring ocean environments with
      complex waves, tides and ocean currents.

PMID- 29042136
TI  - Mercury bioaccumulation in bats reflects dietary connectivity to aquatic food
      webs.
AB  - Mercury (Hg) is a persistent and widespread heavy metal with neurotoxic effects
      in wildlife. While bioaccumulation of Hg has historically been studied in aquatic
      food webs, terrestrial consumers can become contaminated with Hg when they feed
      on aquatic organisms (e.g., emergent aquatic insects, fish, and amphibians).
      However, the extent to which dietary connectivity to aquatic ecosystems can
      explain patterns of Hg bioaccumulation in terrestrial consumers has not been well
      studied. Bats (Order: Chiroptera) can serve as a model system for illuminating
      the trophic transfer of Hg given their high dietary diversity and foraging links
      to both aquatic and terrestrial food webs. Here we quantitatively characterize
      the dietary correlates of long-term exposure to Hg across a diverse local
      assemblage of bats in Belize and more globally across bat species from around the
      world with a comparative analysis of hair samples. Our data demonstrate
      considerable interspecific variation in hair total Hg concentrations in bats that
      span three orders of magnitude across species, ranging from 0.04 mg/kg in
      frugivorous bats (Artibeus spp.) to 145.27 mg/kg in the piscivorous Noctilio
      leporinus. Hg concentrations showed strong phylogenetic signal and were best
      explained by dietary connectivity of bat species to aquatic food webs. Our
      results highlight that phylogeny can be predictive of Hg concentrations through
      similarity in diet and how interspecific variation in feeding strategies
      influences chronic exposure to Hg and enables movement of contaminants from
      aquatic to terrestrial ecosystems.

PMID- 29042137
TI  - Occurrence and indicators of pharmaceuticals in Chinese streams: A nationwide
      study.
AB  - Pharmaceutically active compounds (PhACs) are excreted by humans and animals and
      released into the aquatic environment through wastewater, which can have
      potential negative impacts on ecological systems. To conduct a nationwide
      investigation of the occurrence of PhACs in water resources in China, an
      analytical procedure based on solid-phase extraction (SPE) and LC-MS/MS was used
      to measure 45 PhACs in surface water samples from a network of 29 rivers across
      31 provinces in China in 2014 and 2015. PhACs were prevalent in all sampled
      streams. The concentrations of commonly detected PhACs were comparable to those
      detected in other countries. High total concentrations (mean > 1 MUg L-1) of all
      tested PhACs were primarily detected in areas under extreme water stress,
      specifically northern and eastern coastal areas. Source apportionment based on
      the profiles of the target compounds found that 54% of the PhACs in China
      originated from freshly discharged untreated sewage. Metformin (MET) and its
      biodegradation product, guanylurea (GUL), were used as a pair of indicators to
      predict PhAC contamination levels and differentiate between biotreated and
      unbiotreated wastewater. High MET/GUL can be used to indicate untreated
      wastewater, whereas low MET/GUL values are a strong indicator of treated
      wastewater. Furthermore, wastewater biotreatment ratios were calculated. We
      estimated that the biotreatment ratios of most of the provinces in China were
      less than 50%. We conclude that more attention should be paid to untreated sewage
      water, especially water in rural areas rather than the existing concentration on
      urban sewage treatment-oriented management.

PMID- 29042138
TI  - Managing the excessive proliferation of glycogen accumulating organisms in
      industrial activated sludge by nitrogen supplementation: A FISH-NanoSIMS
      approach.
AB  - Defluviicoccus vanus-related glycogen accumulating organisms (GAO) regularly
      proliferate in industrial wastewater treatment plants handling high carbon but
      nitrogen deficient wastes. When GAO dominate, they are associated with poor
      performance, characterised by slow settling biomass and turbid effluents.
      Although their ecophysiology has been studied thoroughly in domestic waste
      treatment plants, little attention has been paid to them in aerobic industrial
      systems. In this study, the effect of nitrogen addition on GAO carbon metabolism
      was investigated during an 8h cycle. Activated sludge dominated by GAO from a
      winery wastewater sequencing batch reactor was incubated under different carbon
      to nitrogen (COD:N) ratios (100:1, 60:1 and 20:1) using 13C - acetate and 15N -
      urea. GAO cell assimilation was quantified using FISH-NanoSIMS. The activated
      sludge community was assessed by 16S rRNA gene profiling, DNA and storage polymer
      production. Carbon and nitrogen quantification at the cellular level by NanoSIMS
      revealed that low (COD:N of 100:1) or null nitrogen concentrations enhanced GAO
      carbon uptake. COD:N ratios of 60:1 and 20:1 reduced GAO carbon uptake and
      promoted whole microbial community DNA production. Nitrogen dosing at COD:N
      ratios of 60:1 or higher was demonstrated as feasible strategy for controlling
      the excessive GAO growth in high COD waste treatment plants.

PMID- 29042139
TI  - Predictors of functional recovery in first-episode psychosis: A systematic review
      and meta-analysis of longitudinal studies.
AB  - BACKGROUND: Three out of four first-episode psychosis (FEP) patients achieve
      clinical remission following treatment. Unfortunately, functional recovery lags
      behind symptomatic remission, and many individuals with FEP remain socially
      isolated with poor functional outcomes. AIMS: To systematically compile and
      analyse predictors of functional recovery in FEP. METHOD: Systematic review and
      meta-analysis of peer-reviewed, longitudinal studies reporting predictors of
      functioning, with a minimum 12-month follow-up and at least 80% of participants
      diagnosed with FEP. RESULTS: Out of 2205 citations, 274 articles were retrieved
      for detailed evaluation resulting in 50 eligible studies (N=6669).
      Sociodemographic, clinical, physical and neuroimaging variables had little impact
      on long-term functioning. Conversely duration of untreated psychosis (DUP), most
      cognitive variables, and concurrent remission of positive and negative symptoms
      were independently related to functional recovery. CONCLUSIONS: These findings
      strongly support the rationale for early intervention in FEP. Novel treatments
      targeting cognitive deficits may improve functional outcomes in FEP.

PMID- 29042140
TI  - Myeloid cells contribute indirectly to VEGF expression upon hypoxia via
      activation of Muller cells.
AB  - Anti-VEGF-directed therapies have been a milestone for treating retinal vascular
      diseases. Depletion of monocyte lineage cells suppresses pathological
      neovascularization in the oxygen-induced retinopathy mouse model. However, the
      question whether myeloid-derived VEGF-A expression is responsible for the
      pathogenesis in oxygen-induced retinopathy remained unknown. We analyzed LysMCre
      driven myeloid cell-specific VEGF-A knockout mice as well as mice with complete
      depletion of circulating macrophages through clodronate-liposome treatment in the
      oxygen-induced retinopathy model by immunohistochemistry, qPCR, and flow
      cytometry. Furthermore, we analyzed VEGF-A mRNA expression in MIO-M1 cells alone
      and in co-culture with BV-2 cells in vitro. The myeloid cell-specific VEGF-A
      knockout did not change relative retinal VEGF-A mRNA levels, the relative
      avascular area or macrophage/granulocyte numbers in oxygen-induced retinopathy
      and under normoxic conditions. We observed an insignificantly attenuated
      pathology in systemically clodronate-liposome treated knockouts but evident VEGF
      A expression in activated Muller cells on immunohistochemically stained sections.
      MIO-M1 cells had significantly higher expression levels of VEGF-A in co-culture
      with BV-2 cells compared to cultivating MIO-M1 cells alone. Our data show that
      myeloid-derived cells contribute to pathological neovascularization in oxygen
      induced retinopathy through activation of VEGF-A expression in Muller cells.

PMID- 29042141
TI  - Involvement of Bmi-1 gene in the development of gastrointestinal stromal tumor by
      regulating p16Ink4A/p14ARF gene expressions: An in vivo and in vitro study.
AB  - OBJECTIVE: This study was conducted in order to explore the role that Bmi-1 plays
      during the development of a gastrointestinal stromal tumor (GIST) by regulation
      of the p16Ink4A and p14ARF expressions. METHODS: Eighty-six patients diagnosed
      with GIST were selected to take part in this experiment. The Bmi-1 protein
      expressions in GIST and adjacent normal tissues were detected using
      immunohistochemistry and further analyzed by using photodensitometry. To monitor
      and track the progression of the GIST, a 3-year follow-up was conducted for all
      affected patients. After cell transfection, the GIST cells were assigned into the
      control group (without transfection), the negative control (NC) group
      (transfected with Bmi-1-Scramble plasmid), and the Bmi-1 shRNA group (transfected
      with the pcDNA3.1-Bmi-1 shRNA plasmid). Protein and mRNA expressions collected
      from Bmi-1, p16lnk4A, P14ARF, cyclin D1, and CDK4 were measured using both the RT
      qPCR and western blotting methods Cell senescence was assessed and obtained by
      using the beta-Galactosidase (beta-Gal) activity assay. The use of a Soft agar
      colony formation assay and CCK-8 assay were performed in order to detect the cell
      growth and subsequent proliferation. Cell invasion and migration were analyzed
      using the Transwell assay and scratch test. RESULTS: Bmi-1 in the GIST tissues
      was found to be significantly higher and the p16lnk4A and P14ARF expressions were
      lower than those in the adjacent normal tissues. Bmi-1 was negatively correlated
      with p16lnk4A and P14ARF expressions according to the correlation analysis. Bmi-1
      expression was associated with the TNM stage, postoperative recurrence,
      metastasis, tumor size, and the 5-year survival rate. Area under ROC curve was
      calculated at 0.884, and sensitivity, specificity, and accuracy of Bmi-1
      predicting the GIST were 67.44%, 97.67%, and 65.12%, respectively. Patients
      exhibiting a high Bmi-1 expression in the GIST tissues had lower survival rates
      than those with low Bmi-1 expression. In comparison with the control group,
      P14ARF, and p16lnk4A were up-regulated, while cyclinD 1 and CDK4 were down
      regulated, cell senescence was promoted, and cell proliferation, invasion, and
      migration also showed some regression in the Bmi-1 shRNA group. CONCLUSIONS:
      These collection of data indicated that the down-regulated Bmi-1 might inhibit
      the proliferation, invasion, and migration of GIST cells and can be subsequently
      linked to the incidence and developing a prognosis of GIST.

PMID- 29042142
TI  - Fat-brain connections: Adipocyte glucocorticoid control of stress and metabolism.
AB  - Glucocorticoids act via multiple mechanisms to mobilize energy for maintenance
      and restoration of homeostasis. In adipose tissue, glucocorticoids can promote
      lipolysis and facilitate adipocyte differentiation/growth, serving both energy
      mobilizing and restorative processes during negative energy balance. Recent data
      suggest that adipose-dependent feedback may also be involved in regulation of
      stress responses. Adipocyte glucocorticoid receptor (GR) deletion causes
      increased HPA axis stress reactivity, due to a loss of negative feedback signals
      into the CNS. The fat-to-brain signal may be mediated by neuronal mechanisms,
      release of adipokines or increased lipolysis. The ability of adipose GRs to
      inhibit psychogenic as well as metabolic stress responses suggests that (1)
      feedback regulation of the HPA axis occurs across multiple bodily compartments,
      and (2) fat tissue integrates psychogenic stress signals. These studies support a
      link between stress biology and energy metabolism, a connection that has clear
      relevance for numerous disease states and their comorbidities.

PMID- 29042143
TI  - The professional in the lead?

PMID- 29042144
TI  - A comparative surface topographical analysis of explanted total knee replacement
      prostheses: Oxidised zirconium vs cobalt chromium femoral components.
AB  - It has been proposed that an increased surface roughness of the femoral
      components of Total Knee Replacements (TKRs) may be a contributing factor to the
      accelerated wear of the polyethylene (PE) bearing and ultimately prosthesis
      failure. Oxidised Zirconium was introduced to the orthopaedic market in an
      attempt to reduce PE wear associated failures and increase the longevity of the
      prosthesis. In this study, non-contacting profilometry was used to measure the
      surface roughness of the femoral components of 6 retrieved TKRs (3 Oxidised
      Zirconium (OxZr) and 3 Cobalt Chromium alloy (CoCr) femoral components) and 2 as
      manufactured femoral components (1 OxZr and 1 CoCr). A semi-quantitative method
      was used to analyse the damage on the retrieved PE components. The Sa values for
      the retrieved OxZr femoral components (Sa = 0.093 um +/- 0.014) and for the
      retrieved CoCr femoral components (Sa = 0.065 um +/- 0.005) were significantly
      greater (p < .05) than the roughness values for the as-manufactured femoral
      components (OxZr Sa = 0.061 um +/- 0.004 and CoCr Sa = 0.042 um +/- 0.003). No
      significant difference was seen between the surface roughness parameters of the
      retrieved OxZr and retrieved CoCr femoral components. There was no difference
      between the PE component damage scores for the retrieved OxZr TKRs compared to
      the retrieved CoCr TKRs. These results agree with other studies that both OxZr
      and CoCr femoral components roughen during time in vivo but the lack of
      difference between the surface roughness measurements of the two materials is in
      contrast to previous topographical reports. Further analysis of retrieved OxZr
      TKRs is recommended so that a fuller appreciation of their benefits and
      limitations be obtained.

PMID- 29042145
TI  - Electronic-clinical evaluation exercise (e-CEX): A new patient-centered EHR use
      tool.
AB  - INTRODUCTION: Electronic Health Record (EHR) use can enhance or weaken patient
      provider communication. Despite EHR adoption, no validated tool exists to assess
      EHR communication skills. We aimed to develop and validate such a tool. METHODS:
      Electronic-Clinical Evaluation Exercise (e-CEX) is a 10-item-tool based on
      systematic literature review and pilot-testing. Second-year (MS2s) students
      participated in an EHR-use lecture and structured Clinical Examination (OSCE).
      Untrained third-year students (MS3s) participated in the same OSCE. OSCEs were
      scored with e-CEX compared to a standardized patient (SP) tool. Internal
      consistency, discriminant validity, and concurrent validity were analyzed.
      RESULTS: Three investigators used e-CEX to rate 70 videos (20 MS2, 50 MS3).
      Reliability testing indicated high internal consistency (Cronbach's alpha=0.89).
      MS2s scored significantly higher than untrained MS3s on e-CEX [e-CEX 55(10.7) vs.
      44.9 (12.7), P=0.003], providing evidence of discriminant validity. e-CEX and SP
      score correlation was high (Pearson correlation=0.74, P<0.001), providing
      concurrent validity evidence. Item reduction suggested a three-item tool had
      similar explanatory power (R-squared=0.85 vs 0.86). CONCLUSION: e-CEX is a
      reliable, valid tool to assess medical student patient-centered EHR communication
      skills. PRACTICE IMPLICATIONS: While validation is needed with other healthcare
      providers, e-CEX may help improve provider behaviors and enhance patients'
      overall experience of EHR use in their care.

PMID- 29042146
TI  - Is patient behavior during consultation associated with shared decision-making? A
      study of patients' questions, cues and concerns in relation to observed shared
      decision-making in a cancer outpatient clinic.
AB  - OBJECTIVES: To explore how cancer patients actively participate in consultations
      by asking questions and expressing emotional cues/concerns and to what extent
      this is associated with physician shared decision making (SDM) behavior. METHODS:
      This observational study included audio recordings of 31 primary consultation
      with patients at the Oncology Outpatient Clinic at the University Hospital of
      North Norway. The content (topics) and frequency of health related questions from
      patients/caregivers were registered along with emotional cues and concerns (VR
      CoDES) and observed shared decision-making (OPTION). Patient reported outcomes
      were measured before and one week after the consultation. RESULTS: On average, 17
      (SD 15) questions were asked, and 1.9 (SD 1.9) emotional cues and concerns were
      expressed by patients per consultation. The questions mainly pertained to
      treatment and practical issues. The mean OPTION score was 12 (SD 7.9) and was
      neither associated with questions nor emotional cues and concerns from patients.
      CONCLUSION: Although patients were active by asking questions, observed physician
      SDM behavior measured by OPTION was low and not associated with patient behavior
      during consultation. PRACTICE IMPLICATIONS: Further research on patients
      influence on physician SDM behavior is needed.

PMID- 29042147
TI  - How immunotherapies are targeting the glioblastoma immune environment.
AB  - The diagnosis of glioblastoma remains one of the most dismal in medical practice,
      with current standard care only providing a median survival of 14.6 months. The
      need for new therapies is desperately clear. Components of the tumour
      microenvironment are demonstrating growing importance in the field, given they
      allow the tumour to utilise pathways involved in autoimmune prevention, something
      that enables the tumour's establishment and growth. As with many different
      cancers, the search for a new standard has progressed to the design of
      immunotherapies, which aim to counteract the immune changes within this
      microenvironment. Serotherapy, adoptive lymphocyte transfer, peptide and
      dendritic cell vaccines and a range of other methods are currently under
      investigation, while intracranial infection has also been researched for its
      capacity to reverse glioblastoma mediated immunosuppression. Some of these new
      therapies have shown promise, but it is a long road ahead before their
      incorporation into glioblastoma standard therapy.

PMID- 29042148
TI  - Histopathology of 3 Tesla MRI-negative temporal lobe epilepsies.
AB  - INTRODUCTION: Histopathology of MRI-negative temporal lobe epilepsies (TLE) shows
      heterogeneous findings. The use of either 1.5 or 3 Tesla MRI for the selection of
      MRI-negative cases and use of older classification systems instead of the current
      ILAE classification system may account for this heterogeneity. We focus on
      histopathology of 3 Tesla MRI-negative TLE according to ILAE criteria and
      investigate potential correlation to seizure outcome 1 year postoperatively.
      MATERIALS AND METHODS: Twenty specimens (9 neocortical, 11 hippocampal) from
      eleven 3 Tesla MRI-negative patients with TLE were examined in two steps.
      Standard stains and immunohistochemical reactions as well as Palmini and Wyler
      criteria were used prospectively during the initial examination. Retrospectively,
      all specimens were re-examined and re-evaluated. Phospho-6 and calretinin stains
      and the ILAE criteria were used during the review examination. RESULTS: Initial
      examination revealed 7 focal cortical dysplasias (FCDs) Palmini type 1, two cases
      of cortical gliosis, 4 cases of hippocampal sclerosis (HS) Wyler grade 1 and
      seven cases of hippocampal gliosis. The review examination according to ILAE
      criteria revealed 4 FCDs type I and 5 mild malformations of cortical development.
      All hippocampal specimens showed "no HS/gliosis only" after the review
      examination. Histopathology showed no correlation to seizure outcome. DISCUSSION:
      This is the first histopathological study to include only 3 Tesla MRI-negative
      cases. The use of ILAE criteria lead to the diagnosis of "no HS/gliosis only" of
      all hippocampal specimens, a finding not in line with previously reported series.
      The spectrum of diagnoses within neocortical specimens showed accordingly more
      mild findings.

PMID- 29042149
TI  - EGSnrc calculation of activity calibration factors for the Vinten ionization
      chamber.
AB  - The National Physical Laboratory Vinten 671 chamber was selected as a proving
      ground for a new radionuclide source model in the EGSnrc software. The
      computational Vinten model is validated against measurements of radionuclide
      artifacts whose activities were determined by absolute methods. The response of
      the Vinten chamber is first calculated as a function of gamma energy, but more
      strikingly, an explicit simulation of radionuclide decay was implemented and now
      permits the direct determination of a calibration factor, including additional
      effects due to all decay paths of the radionuclide. The Monte Carlo and
      experimental calibration factors are found to agree at the percent level, in
      absolute terms.

PMID- 29042150
TI  - Paul Joyce and the infinite alleles model.
AB  - Paul Joyce's work touched on a variety of topics in population genetics-from
      mathematical models of idealized systems to working closely with biologists on
      experimental evolution and landscape genetics. I will focus on his earlier
      mathematical/statistical work that centered on the infinite alleles model.

PMID- 29042151
TI  - Which treatment modality for pediatric pilonidal sinus: Primary repair or
      secondary healing?
AB  - OBJECTIVE: To evaluate the outcome and characteristics of patients who were
      operated for sacrococcygeal pilonidal sinus (SPS) treatment using primary repair
      or secondary healing technique. METHODS: Forty-seven patients (female: 25, male:
      22) diagnosed with pilonidal sinus operated between 2009 and 2015 were
      retrospectively analyzed. The cases were evaluated for age, gender, body mass
      index (BMI), surgical technique, hospital stay, recovery time and recurrence.
      Mainly two types of surgical techniques were applied: primary repair and
      secondary healing. RESULTS: Mean age of the patients was 15.6 (+/-1.2) years.
      Excision and primary repair was performed in 36, excision and secondary healing
      was in 11. There was no statistically significant difference between the groups
      regarding length of hospital stay and duration of postoperative pain (p > 0.05).
      There was a statistically significant difference between groups regarding
      recovery time (p < 0.05). Recurrence was detected in a total of 11 (23.4%)
      patients. CONCLUSION: We did not find any significant difference concerning
      length of hospitalization, duration of postoperative pain and recurrence rate.
      However we determined that the primary repair group recovery time is
      significantly shorter compared to our secondary healing group. Therefore we
      recommended primary repair in the treatment of primary repair PS in children.

PMID- 29042152
TI  - Crowdsourcing dermatology: DataDerm, big data analytics, and machine learning
      technology.

PMID- 29042153
TI  - Classification of cerebral palsy and potential role of video recording.

PMID- 29042154
TI  - A case-control study of skin conductance biofeedback on seizure frequency and
      emotion regulation in drug-resistant temporal lobe epilepsy.
AB  - This study investigates the physiological basis of effects of skin conductance
      biofeedback on anxiety disorders, depressive disorders and stress in drug
      resistant temporal lobe epilepsy (TLE). This method presents an interest in
      seizure reduction and improvement in psychiatric comorbidities frequently
      associated with TLE. Our goal was to better understand the impact of biofeedback
      on seizure control and on emotional regulation. Fifteen patients with TLE were
      treated with 12 skin conductance biofeedback sessions and compared with 15
      control TLE patients on a waiting list. They were evaluated in terms of seizure
      frequency, clinical evaluations of anxiety and depression and skin conductance
      responses (SCR) to five emotions: fear, disgust, sadness, happiness and
      peacefulness induced by short films. Biofeedback training significantly reduced
      seizure frequency with a mean reduction of -47.42% in the biofeedback group,
      while the control group did not differ at the two time measures. A significant
      improvement was found for depression and trait-anxiety in the biofeedback group
      but not in the control group. There were no differences on SCR on any emotion
      after biofeedback treatment. A correlation was found between mean change in SCR
      over the biofeedback treatment and the reduction of seizure frequency, but not
      between SCR changes and scores on psychiatric comorbidities. These results show
      independent effect of biofeedback on mood and seizure control. Improvements in
      anxiety and depressive symptoms were not related to SCR, whereas improved seizure
      control was, suggesting differential mechanisms underlying these two phenomena.

PMID- 29042155
TI  - Seasonal omalizumab reduces allergen-specific immunoglobulin E levels in patients
      with Japanese cedar pollinosis and asthma.

PMID- 29042156
TI  - Head-turning asymmetry: A novel lateralization in rats predicts susceptibility to
      behavioral despair.
AB  - Behavioral markers of laterality reflecting underlying neurobiological
      asymmetries between the cerebral hemispheres are related to differential
      susceptibility to mood disorders. In the present study, we investigated the
      strength and consistency of a novel behavioral lateralization, head-turning
      asymmetry, and its relation to behavioral despair in adult female Wistar rats.
      Head-turning biases were determined in a test where water-deprived rats had to
      turn their head to right or left to gain access to a water dispenser. This
      procedure was administered 4 times over 8days. Four days after the head-turning
      test, rats were subjected to two forced swim tests separated by 24h to examine
      the relationship between head-turning asymmetry and behavioral despair. Rats were
      administered one more head-turning test session after the second swim test to
      determine whether behavioral despair induction altered head-turning direction
      preferences. Results revealed significant correlations among head-turning test
      sessions indicating head-turning direction preference as measured with our method
      is a consistent behavioral lateralization. Although most rats were strongly
      lateralized, there was no bias in either direction at the population level.
      Importantly, we found that while rats with a left head-turning bias showed a
      significant increase in the duration of immobility from the first to the second
      swim test, right-biased rats performed similarly in the two swim tests.
      Behavioral despair induction did not change head-turning direction preferences.
      The present findings show that head-turning asymmetries are predictive of mood
      disorders in rats and may serve as the basis to elucidate the mechanisms relating
      hemispheric asymmetries to depression in humans.

PMID- 29042157
TI  - Selective inhibition of distracting input.
AB  - We review a series of studies exploring distractor suppression. It is often
      assumed that preparatory distractor suppression is controlled via top-down
      mechanisms of attention akin to those that prepare brain areas for target
      enhancement. Here, we consider two alternative mechanisms: secondary inhibition
      and expectation suppression within a predictive coding framework. We draw on
      behavioural studies, evidence from neuroimaging and some animal studies. We
      conclude that there is very limited evidence for selective top-down control of
      preparatory inhibition. By contrast, we argue that distractor suppression often
      relies secondary inhibition of non-target items (relatively non-selective
      inhibition) and on statistical regularities of the environment, learned through
      direct experience.

PMID- 29042158
TI  - Predictive value of metacarpophalangeal stabilization tests for simulated ulnar
      nerve lesion measured by a sensor glove.
AB  - STUDY DESIGN: A within-subject research design was used in this study. The
      difference of the range of motion (ROM) with and without ulnar nerve block was
      analyzed. INTRODUCTION: For the clinical evaluation of the functional effects of
      ulnar nerve palsy at the hand the relevance of clinical tests is in discussion.
      PURPOSE OF THE STUDY: The aim of the study was to evaluate the predictive value
      of 2 clinical tests for a simulated ulnar nerve lesion by motion analysis with a
      sensor glove. METHODS: In 28 healthy subjects, dynamic measurements of the finger
      joints were performed by a sensor glove with and without ulnar nerve block at the
      wrist. In the 0 degrees  metacarpophalangeal (MCP) stabilization test, the
      subjects were asked to stabilize the MCP joints actively in 0 degrees  while
      moving the interphalangeal joints, whereas at the 90 degrees  MCP stabilization
      test, the subjects stabilized the MCP joints actively in the 90 degrees 
      position. RESULTS: In the 0 degrees  MCP stabilization test, no remarkable
      changes of the ROM were found at the MCP joints; at the proximal interphalangeal
      joints 2-5, the ROM decreased with ulnar nerve block, significantly at the index,
      middle, and ring fingers (P < .05). In the 90 degrees  MCP stabilization test,
      the average ROM of the MCP joints 2-5 significantly increased with ulnar nerve
      block (P < .05), whereas at the PIP joints, the average ROM decreased (P < .05).
      DISCUSSION: The 90 degrees  MCP stabilization test had a high predictive value
      for the discrimination between healthy subjects and subjects with a simulated
      peripheral ulnar nerve lesion. CONCLUSIONS: The results could be relevant for the
      determination of the functional effect of ulnar nerve palsy and the
      quantification of clawing in hand rehabilitation. LEVEL OF EVIDENCE: II.

PMID- 29042159
TI  - Pulley injuries in rock climbers: Hand therapy clinical application.

PMID- 29042160
TI  - Recovery, age, and gender effects on hand dexterity after a distal radius
      fracture. A 1-year prospective cohort study.
AB  - STUDY DESIGN: A prospective cohort study. INTRODUCTION: Physical factors that
      predict hand dexterity and the recovery of hand dexterity after a distal radius
      fracture (DRF) have not yet been examined. PURPOSE OF THE STUDY: The first
      objective was to evaluate the recovery of hand dexterity comparing the injured
      and uninjured hands during the year after a DRF. The second objective was to
      determine the effect of age and sex on hand dexterity of the injured hand.
      METHODS: Hand dexterity was examined bilaterally for the manipulation of 3
      different sized objects (small, medium, and large) using the NK hand dexterity
      test. The measurements took place at 3, 6, and 12 months after DRF. Generalized
      linear modeling was performed, with age and sex as covariates, to assess changes
      over time, and between sides. RESULTS: Overall, 242 patients with DRF (45 males
      and 197 females) with a mean age of 60.2 years with SD of 11.26, participated in
      the study. Statistical differences in hand dexterity were found between the
      injured and uninjured hands across all time intervals (P < .001). The effect size
      for the deficit between the injured and uninjured hands decreased across the time
      intervals and ranged from 0.19 to 0.38 for large objects, from 0.17 to 0.25 for
      medium objects, and from 0.11 to 0.32 for small objects. For each 1-year increase
      in age, hand dexterity scores were 0.3-0.4 seconds slower. Sex had much less
      effect, with annual increases of 0.1 seconds in hand dexterity scores.
      CONCLUSIONS: Scores on the NK dexterity test improved between 3 and 6 months and
      then worsened between 6 and 12 months; at no point did dexterity equal the
      uninjured side. Greater attention to measuring and treating dexterity may be
      needed to provide a complete recovery after DRF. Scores will be affected by age
      and sex. LEVEL OF EVIDENCE: Prognosis, 2a.

PMID- 29042161
TI  - Kinematic evaluation for impairment of skilled hand function in chemotherapy
      induced peripheral neuropathy.
AB  - INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) usually affects
      both sensory and motor function of hands and feet, resulting in impaired skilled
      hand function (e.g., typing a keyboard). However, quantitative and objective
      evaluations for this condition have not been established. PURPOSE OF THE STUDY:
      We evaluated skilled hand function using a kinematic analysis and investigated
      relationships among hand kinematic function and the clinical sensory and motor
      features of CIPN. STUDY DESIGNS: Clinical measurement. METHODS: Twelve CIPN
      patients and 12 age-matched control participants were enrolled. We recorded their
      reach and grasp movements using a three-dimensional measurement system, and
      calculated the normalized jerk of these movements as quantitative indexes of
      skilled hand function. Additionally, we used the number of sequential hand grip
      release cycles in 10 seconds as an evaluation of clinical motor function.
      RESULTS: Our kinematic analyses revealed significant difference in normalized
      jerk of grasp movement (CIPN: 3.7 +/- 0.2, control: 3.4 +/- 0.1; P = .005), but
      this was not the case for reach movement (CIPN: 2.5 +/- 0.1, control: 2.5 +/-
      0.2; P = .43), indicating that the distal part of the forearm is particularly
      affected in CIPN. Such disturbed grasp movement was directly correlated with poor
      scores on the hand grip-release test and the sensory tests. DISCUSSION: We
      revealed deficit impaired hand function objectively and quantitatively in CIPN
      patients using a kinematic analysis. Further, the hand grip test could represent
      such kinematic abnormality and could be useful for evaluating skilled hand
      function of CIPN patients. CONCLUSIONS: Our kinematic and clinical measurements
      objectively and quantitatively evaluate skilled hand function in individuals with
      CIPN in clinical settings. LEVEL OF EVIDENCE: Cross-sectional observational
      study.

PMID- 29042162
TI  - Pronation and supination analysis based on biomechanical signals from Parkinson's
      disease patients.
AB  - In this work, a fuzzy inference model to evaluate hands pronation/supination
      exercises during the MDS-UPDRS motor examination is proposed to analyze different
      extracted features from the bio-mechanical signals acquired from patients with
      Parkinson's disease (PD) in different stages of severity. Expert examiners
      perform visual assessments to evaluate several aspects of the disease. Some
      previous work on this subject does not contemplate the MDS-UPDRS guidelines. The
      method proposed in this work quantifies the biomechanical features examiners
      evaluate. The extracted characteristics are used as inputs of a fuzzy inference
      model to perform an assessment strictly attached to the MDS-UPDRS. The acquired
      signals are processed by techniques of digital signal processing and statistical
      analysis. The experiments were performed in collaboration with clinicians and
      patients from different PD associations and institutions. In total, 210 different
      measurements of patients with PD, plus 20 different measurements of healthy
      control subjects were performed. With objective values rated by several feature
      extraction procedures there is the possibility to track down the disease
      evolution in a patient, and to detect subtle changes in the patient's condition.

PMID- 29042163
TI  - A multilevel reuse system with source separation process for printing and dyeing
      wastewater treatment: A case study.
AB  - This paper proposes a new system of multilevel reuse with source separation in
      printing and dyeing wastewater (PDWW) treatment in order to dramatically improve
      the water reuse rate to 35%. By analysing the characteristics of the sources and
      concentrations of pollutants produced in different printing and dyeing processes,
      special, highly, and less contaminated wastewaters (SCW, HCW, and LCW,
      respectively) were collected and treated separately. Specially, a large quantity
      of LCW was sequentially reused at multiple levels to meet the water quality
      requirements for different production processes. Based on this concept, a
      multilevel reuse system with a source separation process was established in a
      typical printing and dyeing enterprise. The water reuse rate increased
      dramatically to 62%, and the reclaimed water was reused in different printing and
      dyeing processes based on the water quality. This study provides promising leads
      in water management for wastewater reclamation.

PMID- 29042164
TI  - Pediatrics Spanish Registry of Percutaneous Melody Pulmonary Valve Implantation
      in Patients Younger Than 18 Years.
AB  - INTRODUCTION AND OBJECTIVES: A decade has passed since the first Spanish
      percutaneous pulmonary Melody valve implant (PPVI) in March 2007. Our objective
      was to analyze its results in terms of valvular function and possible mid-term
      follow-up complications. METHODS: Spanish retrospective descriptive multicenter
      analysis of Melody PPVI in patients < 18 years from the first implant in March
      2007 until January 1, 2016. RESULTS: Nine centers were recruited with a total of
      81 PPVI in 77 pediatric patients, whose median age and weight were 13.3 years
      (interquartile range [IQR], 9.9-15.4) and 46kg (IQR, 27-63). The predominant
      cardiac malformation was tetralogy of Fallot (n = 27). Most of the valves were
      implanted on conduits, especially bovine xenografts (n = 31). The incidence of
      intraprocedure and acute complications was 6% and 8%, respectively (there were no
      periprocedural deaths). The median follow-up time was 2.4 years (IQR, 1.1-4.9).
      Infective endocarditis (IE) was diagnosed in 4 patients (5.6%), of which 3
      required surgical valve explant. During follow-up, the EI-related mortality rate
      was 1.3%. At 5 years of follow-up, 80% +/- 6.9% and 83% +/- 6.1% of the patients
      were free from reintervention and pulmonary valve replacement. CONCLUSIONS:
      Melody PPVI was safe and effective in pediatric patients with good short- and mid
      term follow-up hemodynamic results. The incidence of IE during follow-up was
      relatively low but was still the main complication.

PMID- 29042165
TI  - Sustained Ventricular Tachycardia After Thoracic Traumatism in a Patient With
      Repaired Tetralogy of Fallot.

PMID- 29042167
TI  - Reply to Pang et al.: "Early detection of brain death using the Bispectral Index
      (BIS) in patients treated by extracorporeal cardiopulmonary resuscitation (E-CPR)
      for refractory cardiac arrest".

PMID- 29042166
TI  - Radiolabeling and preliminary biodistribution study of 99mTc-labeled antibody
      mimetic scaffold protein repebody for initial clearance properties.
AB  - Antibody-mimetic proteins are intensively being developed for biomedical
      applications including tumor imaging and therapy. Among them, repebody is a new
      class of protein that consists of highly diverse leucine-rich repeat (LRR)
      modules. Although all possible biomedical applications with repebody are ongoing,
      it's in vivo biodistribution and excretion pathway has not yet been explored. In
      this study, hexahistidine (His6)-tag bearing repebody (rEgH9) was labeled with
      [99mTc]-tricarbonyl, and biodistribution was performed following intravenous
      (I.V.) or intraperitoneal (I.P.) injection. Repebody protein was radiolabeled
      with high radiolabeling efficiency (>90%) and radiolabeled compound was more than
      99% pure after purification. Biodistribution data indicates radiotracer has a
      rapid clearance from blood and excreted through the kidneys for intravenous
      (I.V.) injection, but comparatively slow clearance for an intraperitoneal (I.P.)
      injection. SPECT-CT images were found to be in agreement with biodistribution
      data, high activity was found inside kidneys. The observed result for rapid blood
      clearance and renal excretion of repebody (rEgH9) provide useful information for
      the further development of therapeutic strategy.

PMID- 29042168
TI  - Autonomous bone reposition around anatomical landmark for robot-assisted
      orthognathic surgery.
AB  - The purpose of this study was to develop a new method for enabling a robot to
      assist a surgeon in repositioning a bone segment to accurately transfer a
      preoperative virtual plan into the intraoperative phase in orthognathic surgery.
      We developed a robot system consisting of an arm with six degrees of freedom, a
      robot motion-controller, and a PC. An end-effector at the end of the robot arm
      transferred the movements of the robot arm to the patient's jawbone. The
      registration between the robot and CT image spaces was performed completely
      preoperatively, and the intraoperative registration could be finished using only
      position changes of the tracking tools at the robot end-effector and the
      patient's splint. The phantom's maxillomandibular complex (MMC) connected to the
      robot's end-effector was repositioned autonomously by the robot movements around
      an anatomical landmark of interest based on the tool center point (TCP)
      principle. The robot repositioned the MMC around the TCP of the incisor of the
      maxilla and the pogonion of the mandible following plans for real orthognathic
      patients. The accuracy of the robot's repositioning increased when an anatomical
      landmark for the TCP was close to the registration fiducials. In spite of this
      influence, we could increase the repositioning accuracy at the landmark by using
      the landmark itself as the TCP. With its ability to incorporate virtual planning
      using a CT image and autonomously execute the plan around an anatomical landmark
      of interest, the robot could help surgeons reposition bones more accurately and
      dexterously.

PMID- 29042169
TI  - Percutaneous Cryoablation of Renal Cell Carcinoma with Sinus Vein Involvement
      Based on Preprocedural Imaging.
AB  - PURPOSE: To assess feasibility, safety, and oncologic outcomes of cryoablation in
      treatment of renal cell carcinoma (RCC) with extension into adjacent renal sinus
      vein. MATERIALS AND METHODS: Review of an internally maintained renal ablation
      registry identified 7 patients (4 men and 3 women; median age 62 y; age range, 45
      91 y) who underwent percutaneous cryoablation of RCC with imaging consistent with
      extension of tumor into an immediately adjacent renal sinus vein. Four of 7 (57%)
      patients had recurrent tumors following prior partial nephrectomy. Three of 7
      patients (43%) had solitary kidneys. RESULTS: Median tumor size was 4.3 cm
      (range, 1.9-5.0 cm). Biopsy showed RCC in 6 of 7 patients. Technical success was
      achieved in 6 of 7 tumors (86%) There was a single Clavien grade 3 major
      complication. Median hospital stay was 1 night (range, 1-3 nights). Follow-up
      imaging performed in the 6 successfully treated patients at median 11 months
      (range, 2-101 months) showed no local tumor progression. In 2 patients with
      solitary kidneys, estimated glomerular filtration rate declined from 63
      mL/min/1.73 m2 to 45 mL/min/1.73 m2 and 67 mL/min/1.73 m2 to 40 mL/min/1.73 m2 at
      101 months and 12 months following treatment, respectively. Estimated glomerular
      filtration rate remained > 60 mL/min/1.73 m2 in the remaining patients.
      CONCLUSIONS: In this small select group of patients, percutaneous cryoablation
      afforded a safe and, based on early outcomes, effective means of providing local
      control of locally invasive RCC. Percutaneous cryoablation may obviate the need
      for nephrectomy in similar patients.

PMID- 29042170
TI  - Safety of CT-Guided Bone Marrow Biopsy in Thrombocytopenic Patients: A
      Retrospective Review.
AB  - PURPOSE: To test the hypothesis that computed tomography (CT)-guided bone marrow
      biopsy in patients with a platelet count between 20,000/uL and 50,000/uL is safe
      and that preprocedure platelet transfusion is unnecessary. MATERIALS AND METHODS:
      This single-center retrospective study included bone marrow biopsies performed
      between May 2009 and May 2016. The study population included 981 patients-age
      range, 15-93 years; average age, 57 years; 505 (51.5%) men; and 476 (48.5%)
      women. One hundred eighty-seven biopsies were performed in patients with a
      platelet count of 20,000-50,000/MUL; 33 were performed in patients with a
      platelet count of < 20,000/MUL. The primary endpoint was hemorrhagic
      complications, Society of Interventional Radiology (SIR) complication class C or
      above. The complication rates in thrombocytopenic patients were compared to
      patients with a platelet count of >= 50,000/uL. Ninety-five percent confidence
      intervals (CIs) for the complication rate in each group were also calculated.
      RESULTS: There were no SIR class C or above postprocedure bleeding-related
      complications, including interventions or transfusions. For patients with a
      platelet count of < 20,000/MUL and of 20,000-50,000/MUL, hemorrhagic
      complications rates were 0% (95% CI: 0-9.1%) and 0% (95% CI: 0-1.6%),
      respectively. CONCLUSIONS: CT-guided bone marrow biopsy is safe in
      thrombocytopenic patients, with a hemorrhagic complication rate below 1.6% for
      patients with a platelet count of 20,000-50,000/MUL. Routine preprocedure
      platelet transfusion may not be necessary for patients with a platelet count of
      20,000-50,000/MUL.

PMID- 29042171
TI  - Development of a Computerized Adaptive Testing System of the Functional
      Assessment of Stroke.
AB  - OBJECTIVE: To develop a computerized adaptive testing system of the Functional
      Assessment of Stroke (CAT-FAS) to assess upper- and lower-extremity (UE/LE) motor
      function, postural control, and basic activities of daily living with optimal
      efficiency and without sacrificing psychometric properties in patients with
      stroke. DESIGN: Simulation study. SETTING: One rehabilitation unit in a medical
      center. PARTICIPANTS: Patients with subacute stroke (N=301; mean age, 67.3+/
      10.9; intracranial infarction, 74.5%). INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: The UE and LE subscales of the Fugl-Meyer Assessment, Postural
      Assessment Scale for Stroke Patients, and Barthel Index. RESULTS: The CAT-FAS
      adopting the optimal stopping rule (limited reliability increase of <.010) had
      good Rasch reliability across the 4 domains (.88-.93) and needed few items for
      the whole administration (8.5 items on average). The concurrent validity (CAT-FAS
      vs original tests, Pearson r=.91-.95) and responsiveness (standardized response
      mean, .65-.76) of the CAT-FAS were good in patients with stroke. CONCLUSIONS: We
      developed the CAT-FAS, and our results support that the CAT-FAS has sufficient
      efficiency, reliability, concurrent validity, and responsiveness in patients with
      stroke. The CAT-FAS can be used to simultaneously assess patients' functions of
      UE, LE, postural control, and basic activities of daily living using, on average,
      no more than 10 items; this efficiency is useful in reducing the assessment
      burdens for both clinicians and patients.

PMID- 29042172
TI  - Effect of Upper Limb Rehabilitation Compared to No Upper Limb Rehabilitation in
      Lung Transplant Recipients: A Randomized Controlled Trial.
AB  - OBJECTIVE: To investigate the effect of a supervised upper limb (UL) program
      (SULP) compared to no supervised UL program (NULP) after lung transplantation
      (LTx). DESIGN: Randomized controlled trial. SETTING: Physiotherapy gym.
      PARTICIPANTS: Participants (N=80; mean age, 56+/-11y; 37 [46%] men) were
      recruited after LTx. INTERVENTIONS: All participants underwent lower limb
      strength thrice weekly and endurance training. Participants randomized to SULP
      completed progressive UL strength training program using handheld weights and
      adjustable pulley equipment. MAIN OUTCOME MEASURES: Overall bodily pain was rated
      on the visual analog scale. Shoulder flexion and abduction muscle strength were
      measured on a hand held dynamometer. Health related quality of life was measured
      with Medical Outcomes Study 36-item Short Form health Survey and the Quick Dash.
      Measurements were made at baseline, 6 weeks, 12 weeks, and 6 months by blinded
      assessors. RESULTS: After 6 weeks of training, participants in the SULP (n=41)
      had less overall bodily pain on the visual analog scale than did participants in
      the NULP (n=36) (mean VAS bodily pain score, 2.1+/-1.3cm vs 3.8+/-1.7cm; P<.001)
      as well as greater UL strength than did participants in the NULP (mean peak
      force, 8.4+/-4.0Nm vs 6.7+/-2.8Nm; P=.037). At 12 weeks, participants in the SULP
      better quality of life related to bodily pain (76+/-17 vs 66+/-26; P=.05), but at
      6 months there were no differences between the groups in any outcome measures. No
      serious adverse events were reported. CONCLUSIONS: UL rehabilitation results in
      short-term improvements in pain and muscle strength after LTx, but no longer-term
      effects were evident.

PMID- 29042173
TI  - Intraoperative anaphylaxis to bacitracin during scleral buckle surgery.

PMID- 29042174
TI  - Results of Upfront Therapy for Marginal Zone Lymphoma.
AB  - BACKGROUND: Marginal zone lymphomas (MZLs) are indolent disorders composed of 3
      subtypes: extranodal marginal zone lymphoma (MALT), splenic marginal zone
      lymphoma (SMZL), and nodal marginal zone lymphoma (NMZL). Early-stage MALT is
      treated with radiotherapy or antibiotics, and advanced MALT and NMZL are managed
      with either watch and wait or chemotherapy. SMZLs are treated with splenectomy or
      rituximab. However, because these approaches have failed to cure patients with
      SMZL and NMZL, we have systematically used upfront chemotherapy for them, as well
      as for advanced MALT. We report the outcomes of this approach. PATIENTS AND
      METHODS: A total of 44 patients with MZL were identified from our database and
      divided into 2 groups. Group 1 (22 with early-stage MALT) patients received
      either radiotherapy (n = 17) or antibiotics with or without surgery (n = 5).
      Group 2 included 9 patients with advanced MALT, 9 with SMZL, and 4 with NMZL.
      Group 2 was treated with FND-R (fludarabine 25 mg/m2 on days 1 to 3, mitoxantrone
      10 mg/m2 on day 1, dexamethasone 20 mg on days 1 to 5, and rituximab 375 mg/m2 on
      day 1; n = 14) or CHOP-R (cyclophosphamide 750 mg/m2 on day 1, doxorubicin 50
      mg/m2 on day 1, vincristine 2 mg intravenous push on day 1, prednisone 100 mg/m2
      orally on days 1 to 5, rituximab 375 mg/m2 on day 1; n = 8), followed by
      maintenance rituximab for 70%. RESULTS: All patients achieved complete remission,
      and only 2 patients in group 1 had developed a relapse at 70 and 75 months. Both
      relapses were stage I MALT that had initially been treated with radiotherapy.
      Both were salvaged with FND-R and remained free of disease at 27 and 39 months
      after the relapse. At 10 years, the failure-free survival for the 44 patients was
      80% and the overall survival was 100%. None of the patients in group 2 developed
      a relapse. The long-term toxicities have been acceptable. CONCLUSIONS: The
      excellent responses using upfront chemotherapy for MZL suggests that this
      disorder is curable. Our results should be confirmed in a prospective trial.

PMID- 29042176
TI  - Effect of V-Y plasty on lip lengthening and treatment of gummy smile.
AB  - The aim of this study was to assess the effect of isolated V-Y plasty on lip
      lengthening and the treatment of gummy smile. An isolated V-Y plasty was
      performed on 14 patients with a gummy smile. In each case, measurements of upper
      lip length and gingival display were recorded from posed-smile photographs taken
      preoperatively and at 1, 3, and 6 months postoperatively. Gingival display
      decreased significantly and lip length increased significantly over all intervals
      investigated. Applying this technique after Le Fort I surgery may be beneficial;
      however, as with other injection or surgical lip lengthening methods, its stand
      alone application should be questioned.

PMID- 29042175
TI  - Calcitriol promotes proangiogenic molecules in keratinocytes in a diabetic foot
      ulcer model.
AB  - Foot ulceration is one of the most common and complex sequelae of diabetes
      mellitus, generally posing a therapeutic challenge due to poor healing responses
      and high rates of complications, including peripheral vascular disease, ischemia
      and infections. Calcitriol, the most active vitamin D metabolite, induces
      antimicrobial peptides production in keratinocytes from diabetic foot ulcers
      (DFU); however, little is known about its effects on angiogenic factors in this
      pathology. Herein we aimed at studying whether calcitriol induces angiogenic
      molecules in keratinocytes under normoxic and hypoxic conditions, and if these
      molecules are able to improve cell migration in vitro. Evaluation of DFU samples
      by immunohistochemistry showed increased VEGF and decreased angiogenin and HIF
      1alpha expression compared to controls, suggesting an altered pattern of
      angiogenic factors in DFU. Interestingly, incubation of keratinocytes with
      calcitriol significantly upregulated VEGFA, HIF-1alpha and angiogenin gene
      expression, while the resulting cell culture media stimulated both endothelial
      cells and keratinocytes migration in an in vitro wound closure assay under a
      normoxic environment (p<0.05). Moreover, the culture media of calcitriol-treated
      keratinocytes stimulated cell migration in a similar extent as exogenous VEGF or
      EGF in endothelial and keratinocytes cells. These results suggest that the
      altered profile of angiogenic molecules in DFU might be improved by local or
      systemic treatment with calcitriol under normoxic conditions, which could
      probably be achieved with hyperbaric oxygen therapy. Given that calcitriol not
      only augments proangiogenic factors but also induces antimicrobial peptides
      expression, this hormone should be further investigated in clinical trials of
      DFU.

PMID- 29042177
TI  - Antibiotic exposure and interpersonal variance mask the effect of ivacaftor on
      respiratory microbiota composition.
AB  - BACKGROUND: G551D is a class III mutation of the cystic fibrosis transmembrane
      regulator (CFTR) that results in impaired chloride channel function in cystic
      fibrosis (CF). Ivacaftor, a CFTR-potentiating agent improves sweat chloride,
      weight, lung function, and pulmonary exacerbation rate in CF patients with G551D
      mutations, but its effect on the airway microbiome remains poorly characterised.
      METHODS: Twenty CF patients with at least one G551D mutation from a single centre
      were recruited to a 4month double-blind, placebo-controlled, crossover study of
      ivacaftor with 28days of active treatment. Sputum microbiota composition was
      assessed by 16S rRNA gene amplicon sequencing and quantitative PCR at five key
      time points, along with regular clinical review, respiratory function assessment,
      and peripheral blood testing. RESULTS: No significant difference in microbiota
      composition was observed in subjects following ivacaftor treatment or placebo
      (PERMANOVA P=0.95, square root ECV=-4.94, 9479 permutations). Microbiota
      composition variance was significantly greater between subjects, than within
      subjects over time (P<0.0001, Mann Whitney U test), and an additional within
      patient paired assessment of microbiota similarity was therefore performed.
      Again, change in microbiota composition was not significantly greater during
      treatment with ivacaftor compared to placebo (Wilcoxon test, P=0.51). A
      significant change in microbiota composition was however associated with any
      change in antibiotic exposure, regardless of whether ivacaftor or placebo was
      administered (P=0.006). In a small, subgroup analysis of subjects whose
      antibiotic exposure did not change within the study period, a significant
      reduction in total bacterial load was observed during treatment with ivacaftor
      (P=0.004, two-tailed paired Student's t-test). CONCLUSIONS: The short-term impact
      of ivacaftor therapy on sputum microbiota composition in patients with G551D
      mutations are modest compared to those resulting from antibiotic exposure, and
      may be masked by changes in antibiotic treatment regimen.

PMID- 29042178
TI  - Patterns of influenza vaccination coverage in the United States from 2009 to
      2015.
AB  - BACKGROUND: Globally, influenza is a major cause of morbidity, hospitalization
      and mortality. Influenza vaccination has shown substantial protective
      effectiveness in the United States. METHODS: We investigated state-level patterns
      of coverage rates of seasonal and pandemic influenza vaccination, among the
      overall population (six months or older) in the U.S. and specifically among
      children (aged between 6 months and 17 years) and the elderly (aged 65 years or
      older), from 2009/10 to 2014/15, and associations with ecological factors. We
      obtained state-level influenza vaccination rates from national surveys, and state
      level socio-demographic and health data from a variety of sources. We employed a
      retrospective ecological study design, and used both linear models and linear
      mixed-effect models to determine the levels of ecological association of the
      state-level vaccinations rates with these factors, both with and without region
      as a factor for the three populations. RESULTS AND CONCLUSIONS: Health-care
      access has a robust, positive association with state-level vaccination rates
      across all populations and models. This highlights a potential population-level
      advantage of expanding health-care access. We also found that prevalence of
      asthma in adults is negatively associated with mean influenza vaccination rates
      in the elderly populations.

PMID- 29042179
TI  - Do we need neuroimaging to treat insomnia effectively?

PMID- 29042180
TI  - Idiopathic REM sleep behavior disorder in the elderly Spanish community: a
      primary care center study with a two-stage design using video-polysomnography.
AB  - OBJECTIVE: To examine the presence and characteristics of idiopathic REM sleep
      behavior disorder (IRBD) in a representative Caucasian sample from the elderly
      community of Lleida, Spain, attending primary care centers. METHODS: Participants
      were individuals aged 60 years or older who underwent routine visits in two
      primary care centers. They underwent a two-stage study; a validated screening
      single question for IRBD diagnosis (RBD1Q) followed by, in those who endorsed
      positive answer, clinical assessment by a neurologist plus video-polysomnography
      (V-PSG). RESULTS: Of 539 individuals (56.4% women, mean age 72.86 +/- 8.20
      years), 28 (5.2%) endorsed positively the RBD1Q. Four of these 28 refused further
      assessments. Four of the 24 remaining subjects underwent clinical assessment but
      refused V-PSG. Of the 20 who underwent clinical assessment plus V-PSG, REM sleep
      was not recorded in four (20%, all four taking antidepressants). V-PSG ruled out
      RBD in 12 subjects who had obstructive sleep apnea (n = 9), periodic limb
      movement disorder in sleep (n = 2) and normal sleep (n = 1). IRBD was diagnosed
      in four individuals giving an estimated prevalence of 0.74% (95% CI = 0.29-1.89).
      They were three men and one woman between 74 and 82 years of age who never
      reported dream-enacting behaviors to their doctors because they thought they
      represented a normal phenomenon despite suffering sleep-related injuries. These
      patients had history of violent sleep behaviors with an interval between
      estimated RBD onset and V-PSG of 4.5 +/- 4.2 years. CONCLUSIONS: IRBD is not
      uncommon in the elderly community and its demographic and clinical profile is
      similar to those diagnosed in sleep centers.

PMID- 29042181
TI  - Opposing roles of PGD2 in GBM.
AB  - BACKGROUND: The World Health Organization classifies glioblastoma (GBM) as a
      grade IV astrocytoma. Despite the advances in chemotherapy, surgery, and
      radiation treatments that improve a patient's length of survival, the overall
      trajectory of the disease remains unchanged. GBM cells produce significant levels
      of various types of bioactive lipids. Prostaglandin D2 (PGD2) influences both pro
      and anti-tumorigenic activities in the cell; however, its role in GBM is
      unclear. Therefore, this study aimed to identify the impact of PGD2 on GBM cell
      activities in vitro. METHODS: First we looked to identify the presence of the
      PGD2 synthesis pathway through RT-PCR, immunohistochemistry, and HPLC-MS/MS in
      three GBM cell lines. Then, to observe PGD2's effects on cell count and
      apoptosis/mitosis (Hoechst 33342 stain), and migration (Transwell Assay), the
      cells were treated in vitro with physiological (<1MUM) and/or supraphysiological
      (>1MUM) concentrations of PGD2 over 72h. HPLC-MS/MS was used to identify the
      lipid composition of patients with either Grade II/III gliomas or GBM. RESULTS:
      We identified the presence of endogenous PGD2 with its corresponding enzymes and
      receptors. Exogenous PGD2 both increased cell count (<1MUM) and decreased cell
      count (10MUM) in a concentration-dependent manner. There were no significant
      effects on apoptosis. A significant decrease in mitotic activity was seen only in
      U251MG, and a significant increase was seen in migration with 5MUM PGD2
      treatments. A very significant increase of PGD2 was seen from Grade II/III
      gliomas to GBM. CONCLUSIONS: Our study demonstrates that prostaglandin D2
      possesses a dynamic, concentration-dependent effect in GBM cell activities. The
      increase of PGD2 production in GBM patients suggests a pro-tumorigenic role of
      PGD2 in glioma growth and invasion. Therefore, prostaglandin signaling in GBM
      requires further investigation to identify new targets for more effective
      therapies.

PMID- 29042183
TI  - Resilience and transition to practice in Direct Entry nursing graduates.
AB  - Resilience may be one factor that influences new graduates transition to
      practice. This pilot study looked at one cohort of Direct Entry Accelerated
      Master's in Nursing graduates and compared the relationship over time between
      their transition to practice experience and their resiliency. Seventeen of 21
      graduates participated in surveys at graduation and then three, six and 12 months
      post-graduation. The survey consisted of four parts: Demographics,
      Educational/Professional Satisfaction Scale (2016), the Casey-Fink Graduate Nurse
      Experience Scale (2004), and the Wagnild & Young Resiliency Scale (1993). The
      results indicated that professional satisfaction fluctuates during the first year
      of practice. At 12 months post-graduation only 57% of the respondents felt their
      education prepared them for the reality of nursing practice. Resilience at 12
      months post-graduation accounts for 79% of the variance in the Casey Fink scores
      at 12 months. Interventions to improve resilience in new nursing graduates may be
      one way to positively impact transition to practice.

PMID- 29042184
TI  - Analysis of substrate binding in individual active sites of bifunctional human
      ATIC.
AB  - Aminoimidazolecarboxamide ribonucleotide formyl transferase (AICARFT): Inosine
      monophosphate cyclohydrolase (IMPCH, collectively called ATIC) is a bifunctional
      enzyme that catalyses the penultimate and final steps in the purine de novo
      biosynthesis pathway. The bifunctional protein is dimeric and each monomer
      contains two different active sites both of which are capable of binding
      nucleotide substrates, this means to a potential total of four distinct binding
      events might be observed. Within this work we used a combination of site-directed
      and truncation mutants of ATIC to independently investigate the binding at these
      two sites using calorimetry. A single S10W mutation is sufficient to block the
      IMPCH active site allowing investigation of the effects of mutation on ligand
      binding in the AICARFT active site. The majority of nucleotide ligands bind
      selectively at one of the two active sites with the exception of xanthosine
      monophosphate, XMP, which, in addition to binding in both AICARFT and IMPCH
      active sites, shows evidence for cooperative binding with communication between
      symmetrically-related active sites in the two IMPCH domains. The AICARFT site is
      capable of independently binding both nucleotide and folate substrates with high
      affinity however no evidence for positive cooperativity in binding could be
      detected using the model ligands employed in this study.

PMID- 29042185
TI  - The impact of open to collaborative care model in cardiovascular surgical unit.
AB  - BACKGROUND: When compared with open care model, a closed one improves patient
      care in intensive care units (ICUs), mixed ICUs, surgical ICUs and trauma
      centers. We wanted to evaluate the benefit of a collaborative care model in
      highly specialized cardiovascular care unit. METHODS: This study was a
      retrospective, observational study conducted in the cardiovascular care unit of a
      teaching hospital. All patients who were above 20 years old and had received
      cardiovascular operation were enrolled for data collection and analysis. RESULTS:
      A total of 270 subjects were enrolled for analysis during the 2-year study
      period. In the collaborative care model, the CVSU length of stay (p = 0.001) and
      CVSU-free days (p = 0.0008) were significantly better than those in an open care
      model. DISCUSSION: The collaborative care model improved postoperative outcome in
      the cardiovascular surgical unit for those needing prolonged ICU care.

PMID- 29042182
TI  - Are endocrine disrupting compounds environmental risk factors for autism spectrum
      disorder?
AB  - Recent research on the etiology of autism spectrum disorder (ASD) has shifted in
      part from a singular focus on genetic causes to the involvement of environmental
      factors and their gene interactions. This shift in focus is a result of the
      rapidly increasing prevalence of ASD coupled with the incomplete penetrance of
      this disorder in monozygotic twins. One such area of environmentally focused
      research is the association of exposures to endocrine disrupting compounds (EDCs)
      with elevated risk for ASD. EDCs are exogenous chemicals that can alter
      endogenous hormone activity and homeostasis, thus potentially disrupting the
      action of sex and other natural hormones at all stages of human development.
      Inasmuch as sex hormones play a fundamental role in brain development and sexual
      differentiation, exposure to EDCs in utero during critical stages of development
      can have lasting neurological and other physiological influences on the
      developing fetus and, ultimately, the child as well as adult. This review will
      focus on the possible contributions of EDCs to autism risk and pathogenesis by
      first discussing the influence of endogenous sex hormones on the autistic
      phenotype, followed by a review of documented human exposures to EDCs and
      associations with behaviors relevant to ASD. Mechanistic links between EDC
      exposures and aberrant neurodevelopment and behaviors are then considered, with
      emphasis on EDC-induced transcriptional profiles derived from animal and cellular
      studies. Finally, this review will discuss possible mechanisms through which EDC
      exposure can lead to persistent changes in gene expression and phenotype, which
      may in turn contribute to transgenerational inheritance of ASD.

PMID- 29042186
TI  - Bacterial biofilm and associated infections.
AB  - Microscopic entities, microorganisms that drastically affect human health need to
      be thoroughly investigated. A biofilm is an architectural colony of
      microorganisms, within a matrix of extracellular polymeric substance that they
      produce. Biofilm contains microbial cells adherent to one-another and to a static
      surface (living or non-living). Bacterial biofilms are usually pathogenic in
      nature and can cause nosocomial infections. The National Institutes of Health
      (NIH) revealed that among all microbial and chronic infections, 65% and 80%,
      respectively, are associated with biofilm formation. The process of biofilm
      formation consists of many steps, starting with attachment to a living or non
      living surface that will lead to formation of micro-colony, giving rise to three
      dimensional structures and ending up, after maturation, with detachment. During
      formation of biofilm several species of bacteria communicate with one another,
      employing quorum sensing. In general, bacterial biofilms show resistance against
      human immune system, as well as against antibiotics. Health related concerns
      speak loud due to the biofilm potential to cause diseases, utilizing both device
      related and non-device-related infections. In summary, the understanding of
      bacterial biofilm is important to manage and/or to eradicate biofilm-related
      diseases. The current review is, therefore, an effort to encompass the current
      concepts in biofilm formation and its implications in human health and disease.

PMID- 29042187
TI  - Exploring patient experiences of a pain management centre: A qualitative study.
AB  - BACKGROUND AND AIMS: To improve care and management of patients with chronic pain
      it is important to understand patients' experiences of treatment, and of the
      people and the environment involved. As chronic pain patients often have long
      relationships with medical clinics and pain management centres, the team and team
      interactions with the patients could impact the treatment outcome. The aim of
      this study was to elicit as honest as possible an account of chronic pain
      patients' experiences associated with their care and feed this information back
      to the clinical team as motivation for improvement. METHODS: The research was
      conducted at a large hospital-based pain management centre. One hundred
      consecutive patients aged 18 years and above, who had visited the centre at least
      once before, were invited to participate. Seventy patients agreed and were asked
      to write a letter, as if to a friend, describing the centre. On completion of the
      study, all letters were transcribed into NVivo software and a thematic analysis
      performed. RESULTS: Six key themes were identified: (i) staff attitude and
      behaviour; (ii) interactions with the physician; (iii) importance of a dedicated
      pain management centre; (iv) personalized care; (v) benefits beyond pain control;
      (vi) recommending the pain management centre. CONCLUSION: The findings suggest
      that the main reasons that patients recommended the centre were: (i) support and
      validation provided by the staff; (ii) provision of detailed information about
      the treatment choices available; (iii) personalized management plan and
      strategies to improve overall quality of life alongside pain control. None of the
      letters criticized the care provided, but eight of seventy reported long waiting
      times for the first appointment as a problem. IMPLICATIONS: Patient views are
      central to improving care. However, satisfaction questionnaires or checklists can
      be intimidating, and restrictive in their content, not allowing patients to offer
      spontaneous feedback. We used a novel approach of writing a letter to a friend,
      which encouraged reporting of uncensored views. The results of the study have
      encouraged the clinical team to pursue their patient management strategies and
      work to reduce the waiting time for a first appointment.

PMID- 29042188
TI  - Network-based brain stimulation selectively impairs spatial retrieval.
AB  - BACKGROUND: Direct brain stimulation via electrodes implanted for intracranial
      electroencephalography (iEEG) permits the modulation of endogenous electrical
      signals with significantly greater spatial and temporal specificity than non
      invasive approaches. It also allows for the stimulation of deep brain structures
      important to memory, such as the hippocampus, that are difficult, if not
      impossible, to target non-invasively. Direct stimulation studies of these deep
      memory structures, though, have produced mixed results, with some reporting
      improvement, some impairment, and others, no consistent changes.
      OBJECTIVE/HYPOTHESIS: We hypothesize that to modulate cognitive function using
      brain stimulation, it is essential to modulate connected nodes comprising a
      network, rather than just alter local activity. METHODS: iEEG data collected
      while patients performed a spatiotemporal memory retrieval task were used to map
      frequency-specific, coherent oscillatory activity between different brain regions
      associated with successful memory retrieval. We used these to identify two target
      nodes that exhibited selectively stronger coupling for spatial vs. temporal
      retrieval. In a subsequent session, electrical stimulation - theta-bursts with a
      fixed phase-lag (0 degrees  or 180 degrees ) - was applied to the two target
      regions while patients performed spatiotemporal retrieval. RESULTS: Stimulation
      selectively impaired spatial retrieval while not affecting temporal retrieval,
      and this selective impairment was associated with theta decoupling of the spatial
      retrieval network. CONCLUSION: These findings suggest that stimulating tightly
      connected nodes in a functional network at the appropriate phase-lag may
      effectively modulate the network function, and while in this case it impaired
      memory processes, it sets a foundation for further network-based perturbation
      studies.

PMID- 29042189
TI  - Dietary disinhibition mediates the relationship between poor sleep quality and
      body weight.
AB  - BACKGROUND: Inadequate sleep independently influences eating habits and weight
      status. However, the relationship between these three factors has not been well
      quantified. The objective of this study was to examine if eating behavior (i.e.
      dietary restraint, disinhibition and hunger) mediates the relationship between
      sleep and body mass index (BMI) in a large sample of American adults. METHOD:
      Cross-sectional data from the Nathan Kline Institute Rockland sample were
      assessed (n = 602; 38.9 +/- 14.5 years). Self-reported sleep and eating behavior
      were measured using the Pittsburgh Sleep Quality Index and Three Factor Eating
      Questionnaire, respectively. Path analysis was used to examine relationships
      amongst the construct, with mediation tested via bootstrapped confidence
      intervals. RESULTS: Poorer sleep quality was associated with both greater hunger
      (P = 0.03) and higher disinhibited eating (overeating in the presence of
      palatable foods or other disinhibiting stimuli like emotional stress; P < 0.001)
      behaviors. Higher disinhibited eating behavior was also associated with higher
      BMI (P < 0.001). There was a significant indirect relationship between sleep
      quality and BMI via disinhibition (b [95% CI] = 0.13 [0.06, 0.21], P = 0.001). No
      significant effects were found when total sleep time or time in bed were replaced
      as predictors in the mediation model. CONCLUSION: Disinhibited eating behavior
      mediated the relationship between sleep quality and weight status in both males
      and females. This mediation was due to aspects of sleep quality other than
      duration. These results suggest that improving sleep quality may benefit weight
      loss by helping to reduce an individuals' susceptibility to overeating.

PMID- 29042190
TI  - Hematopoietic stem/progenitor involvement in retinal microvascular repair during
      diabetes: Implications for bone marrow rejuvenation.
AB  - The widespread nature of diabetes affects all organ systems of an individual
      including the bone marrow. Long-term damage to the cellular and extracellular
      components of the bone marrow leads to a rapid decline in the bone marrow
      hematopoietic stem/progenitor cells (HS/PCs) compartment. This review will
      highlight the importance of bone marrow microenvironment in maintaining bone
      marrow HS/PC populations and the contribution of these key populations in
      microvascular repair during the natural history of diabetes. The autonomic
      nervous system can initiate and propagate bone marrow dysfunction in diabetes.
      Systemic pharmacological strategies designed to protect the bone marrow-HS/PC
      population from diabetes induced-oxidative stress and advanced glycation end
      product accumulation represent a new approach to target diabetic retinopathy
      progression. Protecting HS/PCs ensures their participation in vascular repair and
      reduces the risk of vasogdegeneration occurring in the retina.

PMID- 29042191
TI  - Roadmap to Achieve 25% Hypertension Control in Africa by 2025.
AB  - BACKGROUND: The Pan-African Society of Cardiology (PASCAR) has identified
      hypertension as the highest area of priority action to reduce heart disease and
      stroke on the continent. OBJECTIVES: The aim of this PASCAR roadmap on
      hypertension was to develop practical guidance on how to implement strategies
      that translate existing knowledge into effective action and improve detection,
      treatment and control of hypertension and cardiovascular health in sub-Saharan
      Africa (SSA) by the year 2025. METHODS: Development of this roadmap started with
      the creation of a consortium of experts with leadership skills in hypertension.
      In 2014, experts in different fields, including physicians and nonphysicians,
      were invited to join. Via face-to-face meetings and teleconferences, the
      consortium made a situation analysis, set a goal, identified roadblocks and
      solutions to the management of hypertension and customized the World Heart
      Federation roadmap to Africa. RESULTS: Hypertension is a major crisis on the
      continent but very few randomized controlled trials have been conducted on its
      management. Also, only 25.8% of the countries have developed or adopted
      guidelines for management of hypertension. Other major roadblocks are either
      government and health-system related or health care professional or patient
      related. The PASCAR hypertension task force identified a 10-point action plan to
      be implemented by African ministries of health to achieve 25% control of
      hypertension in Africa by 2025. CONCLUSIONS: Hypertension affects millions of
      people in SSA and if left untreated, is a major cause of heart disease and
      stroke. Very few SSA countries have a clear hypertension policy. This PASCAR
      roadmap identifies practical and effective solutions that would improve
      detection, treatment and control of hypertension on the continent and could be
      implemented as is or adapted to specific national settings.

PMID- 29042192
TI  - An immune-related gene expression atlas of the shrimp digestive system in
      response to two major pathogens brings insights into the involvement of hemocytes
      in gut immunity.
AB  - Much of our current knowledge on shrimp immune system is restricted to the
      defense reactions mediated by the hemocytes and little is known about gut
      immunity. Here, we have investigated the transcriptional profile of immune
      related genes in different organs of the digestive system of the shrimp
      Litopenaeus vannamei. First, the tissue distribution of 52 well-known immune
      related genes has been assessed by semiquantitative analysis in the
      gastrointestinal tract (foregut, midgut and hindgut) and in the hepatopancreas
      and circulating hemocytes of shrimp stimulated or not with heat-killed bacteria.
      Then, the expression levels of 18 genes from key immune functional categories
      were quantified by fluorescence-based quantitative PCR in the midgut of animals
      experimentally infected with the Gram-negative Vibrio harveyi or the White spot
      syndrome virus (WSSV). Whereas the expression of some genes was induced at 48 h
      after the bacterial infection, any of the analyzed genes showed to be modulated
      in response to the virus. Whole-mount immunofluorescence assays confirmed the
      presence of infiltrating hemocytes in the intestines, indicating that the
      expression of some immune-related genes in gut is probably due to the migratory
      behavior of these circulating cells. This evidence suggests the participation of
      hemocytes in the delivery of antimicrobial molecules into different portions of
      the digestive system. Taken all together, our results revealed that gut is an
      important immune organ in L. vannamei with intimate association with hemocytes.

PMID- 29042193
TI  - MicroRNA-126-3p attenuates blood-brain barrier disruption, cerebral edema and
      neuronal injury following intracerebral hemorrhage by regulating PIK3R2 and Akt.
AB  - MiR-126, a microRNA implicated in blood vessel integrity, angiogenesis and
      vascular inflammation, is markedly decreased in the sera of patients with
      intracerebral hemorrhage (ICH). The current study aims to evaluate the potential
      therapeutic effect of miR-126-3p on brain injuries in a rat model of collagenase
      induced ICH. Intracerebroventricular administration of a miR-126-3p mimic
      significantly alleviated behavioral defects 24 h after ICH, as examined by paw
      placement and corner tests. ICH led to increased blood-brain barrier (BBB)
      permeability and cerebral edema, both of which were attenuated by miR-126-3p
      mimic. Treatment with miR-126-3p mimic reduced the numbers of myeloperoxidase
      (MPO)-positive, OX42-positive, Fluoro Jade B (FJB)-positive and NEUN/TUNEL double
      positive cells around the hematoma, implying that miR-126-3p inhibited neutrophil
      infiltration, microglial activation and neuronal apoptosis following hemorrhage.
      In addition, miR-126-3p mimic suppressed the upregulation of phosphoinositide-3
      kinase regulatory subunit 2 (PIK3R2) in the perihematomal area and maintained the
      activation of Akt. Furthermore, in vitro assays confirmed upregulation of PIK3R2
      upon knockdown of miR-126-3p in rat brain microvascular endothelial cells
      (BMECs), and silencing of miR-126-3p resulted in impaired BMEC barrier
      permeability and reversed vascular endothelial growth factor (VEGF)- and
      angiopoietin-1 (Ang-1)-induced activation of Akt and inhibition of BMEC
      apoptosis. In summary, our results suggest that exogenous miR-126-3p may
      alleviate BBB disruption, cerebral edema and neuronal injury following ICH by
      targeting PIK3R2 and the Akt signaling pathway in brain vascular endothelium.

PMID- 29042194
TI  - Knockdown of RMI1 impairs DNA repair under DNA replication stress.
AB  - RMI1 (RecQ-mediated genome instability protein 1) forms a conserved BTR complex
      with BLM, Topo IIIalpha, and RMI2, and its absence causes genome instability. It
      has been revealed that RMI1 localizes to nuclear foci with BLM and Topo IIIalpha
      in response to replication stress, and that RMI1 functions downstream of BLM in
      promoting replication elongation. However, the precise functions of RMI1 during
      replication stress are not completely understood. Here we report that RMI1
      knockdown cells are hypersensitive to hydroxyurea (HU). Using comet assay, we
      show that RMI1 knockdown cells exhibit accumulation of broken DNAs after being
      released from HU treatment. Moreover, we demonstrate that RMI1 facilitates the
      recovery from activated checkpoint and resuming the cell cycle after replicative
      stress. Surprisingly, loss of RMI1 results in a failure of RAD51 loading onto DNA
      damage sites. These findings reveal the importance of RMI1 in response to
      replication stress, which could explain the molecular basis for its function in
      maintaining genome integrity.

PMID- 29042195
TI  - Circular RNA WDR77 target FGF-2 to regulate vascular smooth muscle cells
      proliferation and migration by sponging miR-124.
AB  - Increasing evidences have revealed the important role of circular RNAs (circRNAs)
      in cardiovascular system disease. Whereas, the expression profiles and in-depth
      regulation of circRNAs on vascular smooth muscle cells (VSMCs) is still
      undetermined. In present study, our research team performed circRNAs microarray
      analysis to present the circRNAs expression profiles in high glucose induced
      VSMCs in vitro. Results showed that total of 983 circRNAs were discovered to be
      differentially expressed, and of these, 458 were upregulated and 525 were
      downregulated. Moreover, 31 circRNAs were up-regulated and 22 circRNAs were down
      regulated with 2 fold change (P < 0.05). One of an up-regulated circRNA,
      circWDR77, was identified. In vitro cell assay, circWDR77 silencing significantly
      inhibited the proliferation and migration. Bioinformatics methods discovered that
      miR-124 and fibroblast growth factor 2 (FGF-2) were downstream targets of
      circWDR77. The RNA sequence complementary binding was validated by RNA
      immunoprecipitation (RIP) and/or luciferase reporter assay. Further function
      validation experiments revealed that circWDR77 regulated VSMCs proliferation and
      migration via targeting miR-124/FGF2. Taken together, present study firstly
      reveals the circRNAs expression profiles in high glucose induced VSMCs and
      identifies the role of circWDR77-miR-124-FGF2 regulatory pathway in VSMCs
      proliferation and migration, which might provide a new theoretical basis for
      diabetes mellitus correlated vasculopathy.

PMID- 29042196
TI  - DCIR3 and DCIR4 are co-expressed on inflammatory and patrolling monocytes.
AB  - Dendritic cell inhibitory receptor 3 (DCIR3) is a member of dendritic immuno
      receptor family, of which protein expression has been unknown. We established a
      specific monoclonal antibody against mouse DCIR3 and investigated the expression
      of DCIR3 on immune cells of various immune organs. We found that DCIR3 was
      expressed on monocytes, but not on eosinophils and neutrophils. We also found the
      existence of a dichotomy in the levels of the expression of DCIR3 on monocytes in
      bone marrow, blood and spleen. Further investigation of the expression of several
      cell surface markers on DCIR3High cells and DCIR3Low cells revealed that
      DCIR3High cells were Ly-6C- CD43High CD11c+ CD80+ NK1.1+ patrolling monocytes and
      that DCIR3Low cells were Ly-6C+ CD43Low CD11c- CD80- NK1.1- inflammatory
      monocytes. These results and our previous finding that DCIR4 is expressed at high
      level in patrolling monocytes and at a low level in inflammatory monocytes
      (Kameda et al., 2016) suggest that DCIR3 and DCIR4 are simultaneously expressed
      on monocytes. Indeed, DCIR4+ CD11b+ monocytes from various immune organs
      expressed DCIR3. We also found that DCIR1 was expressed on DCIR4Low inflammatory
      monocytes but not on DCIR4HIgh patrolling monocytes. The anti- DCIR3 antibody
      established in this study, together with the previously established anti-DCIR1
      and anti-DCIR4 antibodies, would be a valuable tool to investigate biology and
      pathophysiology of monocytes.

PMID- 29042197
TI  - Functional innervation of human induced pluripotent stem cell-derived
      cardiomyocytes by co-culture with sympathetic neurons developed using a
      microtunnel technique.
AB  - Microelectrode array (MEA) based-drug screening with human induced pluripotent
      stem cell-derived cardiomyocytes (hiPSCM) is a potent pre-clinical assay for
      efficiently assessing proarrhythmic risks in new candidates. Furthermore,
      predicting sympathetic modulation of the proarrhythmic side-effects is an
      important issue. Although we have previously developed an MEA-based co-culture
      system of rat primary cardiomyocyte and sympathetic neurons (rSNs), it is unclear
      if this co-culture approach is applicable to develop and investigate sympathetic
      innervation of hiPSCMs. In this study, we developed a co-culture of rSNs and
      hiPSCMs on MEA substrate, and assessed functional connections. The inter-beat
      interval of hiPSCM was significantly shortened by stimulation in SNs depending on
      frequency and pulse number, indicating functional connections between rSNs and
      hiPSCM and the dependency of chronotropic effects on rSN activity pattern. These
      results suggest that our co-culture approach can evaluate sympathetic effects on
      hiPSCMs and would be a useful tool for assessing sympathetic modulated
      cardiotoxicity in human cardiac tissue.

PMID- 29042198
TI  - Two-stage vertical flow multi-soil-layering (MSL) technology for efficient
      removal of coliforms and human pathogens from domestic wastewater in rural areas
      under arid climate.
AB  - This paper investigates the removal efficiency of organic matter, nitrogen,
      phosphorus, coliforms and pathogens from rural domestic wastewater in a two-stage
      vertical flow multi-soil-layering (MSL) system. The effects of wastewater
      quality, season and arid climate conditions on pollutants removal efficiency by
      the system were examined for one year. The experimental setup included two
      similar MSL systems composed of two layers: soil-mixture-layers (SML) and gravel
      permeable layers (PL) that are arranged in a brick like pattern. The applied
      hydraulic loading rate was 1000Lm-2day-1. Results showed that most of the
      physicochemical contaminants elimination occurred while the wastewater percolated
      through the first MSL stage. The second stage demonstrated an improvement in the
      reduction of all pollutants, especially fecal bacteria indicators and pathogens.
      The mean overall removal rates performed by the two-stage MSL system were 97% for
      TSS, 96% for BOD5, 91% for COD, 96% for TN and 95% for TP. For bacterial
      indicators, the combination of two-stage MSL system achieved high log removals
      between 2.21 and 3.15 log units. Contaminants reduction processes in MSL
      technology are more dependent on internal than external environmental factors.
      The effectiveness of the two-stage MSL system to treat domestic wastewater was
      strongly influenced by wastewater quality. Significant relationships between
      influent contaminants level and their removal efficiency were found. The
      efficiency of MSL technology to reduce contaminants is not sensitive to season
      and air temperature fluctuations. This is due to the capacity of MSL system
      materials to withstand the air temperature variation, which highlights one of the
      advantages of MSL's technology. Wastewater quality is the most important factor
      affecting the removal of contaminants in the MSL, which could be a critical
      parameter to considered when designing MSL system. Two-stage MSL system achieved
      a high treated wastewater quality amenable for treated wastewater reuse in
      agriculture recommended by Moroccan code of practice. Therefore, the combination
      of two-stage vertical flow MSL system could be considered an efficient and
      promising domestic wastewater treatment solution in arid countries to promote
      environmental protection and wastewater reuse.

PMID- 29042199
TI  - Temporal expression and gonadotropic regulation of aromatase and estrogen
      receptors in the ovary of wall lizard, Hemidactylus flaviviridis: Correlation
      with plasma estradiol and ovarian follicular development.
AB  - The current study in Indian wall lizard Hemidactylus flaviviridis for the first
      time demonstrates the reproductive phase-dependent expression pattern of
      aromatase (cyp19) and estrogen receptor subtypes (er-alpha and er-beta) as well
      as their gonadotropic regulation in the ovary of a squamate. The expression of
      cyp19 remained low during regressed phase, increased markedly in recrudescent and
      declined sharply in breeding phase. Further, temporal profile of plasma estradiol
      17-beta (E2) was found to be relatively parallel to the expression pattern of
      ovarian cyp19. The expression pattern of estrogen receptors in the ovary showed
      subtype-specific variation along the reproductive cycle. Expression of ovarian er
      alpha remained high from regressed to late recrudescence, while er-beta
      expression that was low during regression dramatically increased with the
      initiation of follicular growth in early recrudescence and remained high until
      late recrudescence. Nonetheless, expression of both the receptors declined during
      breeding phase when ovary contained vitellogenic follicle. Regarding gonadotropic
      regulation, short-term treatment with Follicle stimulating hormone (3 injections
      of FSH) increased the ovarian expression of cyp19, er-alpha and er-beta while
      prolongation of treatment (7 or 11 injections) resulted in a marked decrease in
      expression of these genes concomitant to formation of vitellogenic follicle.
      However, a marked increase in plasma E2 was recorded after 7 injections of FSH.
      The direct role of gonadotropin in regulation of cyp19 and estrogen receptors was
      established by an in vitro study where FSH upregulated the expression of these
      genes in all stages of ovarian follicles (early growing, previtellogenic and
      early vitellogenic) of wall lizards.

PMID- 29042200
TI  - Announcing the publication of the WHO immunological basis for immunization series
      module on influenza vaccines.
AB  - In 2017, the World Health Organization (WHO) published a document aimed at
      facilitating influenza vaccine introduction and use in low- and middle-income
      countries. The document "The Immunological Basis for Immunization Series:
      Influenza Vaccines" is freely available on the WHO website. The main purpose of
      this document is to give immunization managers and vaccination professionals an
      authoritative but easily-understood overview of the scientific basis of influenza
      vaccination and the immunological basis for the WHO position on influenza
      vaccines. The influenza vaccine document comprises one module of the WHO
      Immunological Basis for Immunization series. We invite the immunization community
      to use these references, and we hope the influenza vaccine module will be a
      valuable resource for persons who manage and monitor influenza vaccine programs,
      particularly in low- and middle-income countries.

PMID- 29042201
TI  - Newcastle disease virus (NDV) recombinant expressing the hemagglutinin of H7N9
      avian influenza virus protects chickens against NDV and highly pathogenic avian
      influenza A (H7N9) virus challenges.
AB  - The emerged highly pathogenic avian influenza A (H7N9) (HPAI) viruses in China
      pose a dual challenge to public health and poultry industry. Thus H7N9 vaccines
      are in an urgent need. In this study, we constructed a Newcastle disease virus
      (NDV)-vectored vaccine (rLXHAF) expressing the hemagglutinin (HA) of H7N9 virus
      fused with the transmembrane/cytoplasmic tail domain of the NDV fusion protein.
      rLXHAF stably expressed the HA protein, exhibited similar growth kinetics and
      pathogenicity as the parental virus. rLXHAF induced positive NDV-specific
      hemagglutination inhibition (HI), virus neutralization (VN) and total IgY
      antibodies and completely protected chickens from NDV challenge. Unexpectedly,
      rLXHAF elicited undetectable HI and VN titers but high overall IgY antibody
      titers against H7N9 measured by ELISA. The vaccine provided 80% protection
      against HPAI H7N9 challenge. Virus shedding of NDV and H7N9 challenge strains was
      reduced. Our results suggest that rLXHAF is immunogenic and efficacious against
      HPAI H7N9 virus in chickens.

PMID- 29042202
TI  - Efficacy of the oral rabies virus vaccine strain SPBN GASGAS in foxes and raccoon
      dogs.
AB  - To test the immunogenicity and efficacy of a new oral rabies virus vaccine strain
      SPBN GASGAS in wildlife target species, one group of foxes and two groups of
      raccoon dogs were offered a bait containing 1.7 ml of the vaccine (106.6 FFU/ml;
      106.8 FFU/dose) and subsequently challenged approximately 180 days later with a
      fox rabies virus isolate. One group of raccoon dogs (n=30) received the same
      challenge dose (100.7 MICLD50/ml) as the red foxes (n=29). The other group with
      raccoon dogs (n=28) together with 8 animals that received the vaccine dose by
      direct instillation into the oral cavity (DIOC) were infected with a 40-fold
      higher dose of the challenge virus (102.3 MICLD50/ml). All but one of the 29
      vaccinated foxes survived the challenge infection; meanwhile all 12 control foxes
      succumbed to rabies. Twenty-eight of 30 vaccinated raccoon dogs challenged with
      the same dose survived the infection, however only six of 12 control animals
      succumbed. When the higher challenge dose was administered, all 12 control
      animals died from rabies and all 36 vaccinated animals (28 baited plus 8 DIOC)
      survived. Blood samples were collected at different time points post vaccination
      and examined by both RFFIT and ELISA. The kinetics of the measured immune
      response was similar for both species, although in RFFIT slightly higher values
      were observed in foxes than in raccoon dogs. However, the immune response as
      measured in ELISA was identical for both species. The oral rabies virus vaccine
      SPBN GASGAS meets the efficacy requirements for live rabies virus vaccines as
      laid down by the European Pharmacopoeia.

PMID- 29042203
TI  - Association of antibodies to Plasmodium falciparum merozoite surface protein-4
      with protection against clinical malaria.
AB  - Identification of parasite antigens targeted by immune effector mechanisms that
      confer protection against malaria is important for the design of a multi
      component malaria vaccine. Here, the association of antibodies reacting with the
      Plasmodium falciparum merozoite surface protein-4 (MSP4) with protection against
      clinical malaria was investigated in a Senegalese community living in an area of
      moderate, seasonal malaria transmission. Blood samples were collected at the end
      of an 8-month long dry season without any recorded parasite transmission from 206
      residents enrolled in a prospective follow-up study. Active daily clinical
      monitoring was implemented during the subsequent five months. Entomologic
      monitoring documented parasite transmission during the first three months of
      follow-up. Serum IgG levels were determined by ELISA against three MSP4
      baculovirus-encoded recombinant protein constructs, namely the full-length
      MSP4p40, MSP4p30 devoid of a highly polymorphic sequence stretch and the
      conserved C-terminal EGF-containing MSP4p20, as well as against a merozoite crude
      extract. Community seroprevalence against all three constructs was quite high,
      the lowest being against MSP4p30. Seroprevalence and antibody levels against the
      three MSP4 constructs were age-dependent. IgG1 dominated the anti-MSP4p20
      responses, while both IgG1 and IgG3 were observed against MSP4p40. Anti-MSP4
      antibodies were associated with the antibody-dependent respiratory burst (ADRB)
      activity in a functional assay of merozoite phagocytosis by polymorphonuclear
      cells. Importantly, high antibody levels against each of the three MSP4
      constructs at the end of the dry season were associated with reduced morbidity
      during the subsequent transmission season in an age-adjusted Poisson regression
      model (IRR = 0.65 [0.50-0.83], P<0.001 for responses over the median values).
      These data are consistent with a protective role for the naturally acquired anti
      MSP4 antibodies and support further development of MSP4 as a candidate component
      of malaria vaccine.

PMID- 29042204
TI  - Antibody response to human papillomavirus vaccination and natural exposure in
      individuals with Fanconi Anemia.
AB  - Fanconi anemia (FA) is a rare genetic disorder associated with predisposition to
      head and neck and gynecological squamous cell cancers. In the general population,
      these cancers are commonly linked to human papillomavirus (HPV) infection.
      Antibodies to natural HPV infection and HPV vaccination were evaluated in 63
      individuals with FA while considering host immune factors. Approximately 30% of
      reportedly unvaccinated participants were seropositive (HPV6-38%, HPV11-25%,
      HPV16-26%, and HPV18-26%). Seropositivity was significantly associated with
      having had sex regardless of age (p=.007). Most participants showed
      seropositivity after HPV vaccination (HPV6-100%, HPV11-100%, HPV16-100% and HPV18
      92%). Interestingly, titers for all 4 subtypes were significantly lower in the
      post-hematopoietic stem cell transplant (HSCT) participants compared to those who
      received the vaccine, but had not undergone HSCT (HPV6-p=.030, HPV11-p=.003,
      HPV16-p=.018, HPV18-p=<.001). It is unclear if these titers sufficiently protect
      from new infection since protective serologic cut offs have not yet been defined
      for the HPV vaccine. Individual immune functions were not associated with HPV
      seropositivity, however, underlying heterogeneous immune deficiency may explain
      higher rates of seropositivity in our younger unvaccinated participants (age 4-13
      years). To better measure the efficacy of HPV vaccination in those with FA and
      other immune-compromised or cancer-prone disorders, future well-controlled
      vaccine studies are required.

PMID- 29042205
TI  - Postnatal administration of memantine rescues TNF-alpha-induced decreased
      hippocampal precursor proliferation.
AB  - Pro-inflammatory cytokine exposure in early postnatal life triggers clear
      neurotoxic effects on the developing hippocampus. Tumor necrosis factor alpha
      (TNF-alpha) is one of the inflammatory mediators and is a potent inhibitor of
      neurogenesis. Memantine (MEM) is an uncompetitive N-methyl-d-aspartate (NMDA)
      receptor antagonist that has been demonstrated to increase the proliferation of
      hippocampal progenitor cells. However, the effects of MEM on TNF-alpha-mediated
      impairment of hippocampal precursor proliferation remain unclear. In this study,
      mice were exposed to TNF-alpha and later treated with MEM to evaluate its
      protective effects on TNF-alpha-mediated toxicity during hippocampal development.
      The results indicated that brief exposure to TNF-alpha on postnatal days 3 and 5
      resulted in a significant impairment of hippocampal precursor proliferation and a
      depletion of hippocampal neural precursor cells (NPCs). This effect was
      attenuated by MEM treatment. We further confirmed that MEM treatment reversed the
      TNF-alpha-induced microglia activation and up-regulation of hippocampal NF
      kappaB, MCP-1 and IL-6 mRNA levels, which may be related to the proliferation and
      maintenance of NPCs. Overall, our results suggest that MEM treatment protects
      against TNF-alpha-induced repression of hippocampal precursor proliferation in
      postnatal mice by partially attenuating neuroinflammatory responses.

PMID- 29042206
TI  - Alpha-asarone attenuates depression-like behavior in nicotine-withdrawn mice:
      Evidence for the modulation of hippocampal pCREB levels during nicotine
      withdrawal.
AB  - In the present study, the effect alpha-asarone on nicotine withdrawal-induced
      depression-like behavior in mice was investigated. In this study, mice were
      exposed to drinking water or nicotine solution (10-200ug/ml) as a source of
      drinking for forty days. During this period, daily fluid consumption, food intake
      and body weight were recorded. The serum cotinine level was estimated before
      nicotine withdrawal. Naive mice or nicotine-withdrawn mice were treated with
      alpha-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) for eight
      consecutive days and the forced swim test (FST) or locomotor activity test was
      conducted. In addition, the effect of alpha-asarone or bupropion on the
      hippocampal pCREB, CREB and BDNF levels during nicotine-withdrawal were measured.
      Results indicated that alpha-asarone (5, 10 and 20mg/kg, i.p.) or bupropion
      (10mg/kg, i.p.) pretreatment did not significantly alter the immobility time in
      the FST or spontaneous locomotor activity in naive mice. However, the immobility
      time of nicotine-withdrawn mice was significantly attenuated with alpha-asarone
      (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment in the FST.
      Besides, alpha-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.)
      pretreatment significantly attenuated the hippocampal pCREB levels in nicotine
      withdrawn mice. Overall, the present results indicate that alpha-asarone
      treatment attenuated the depression-like behavior through the modulation of
      hippocampal pCREB levels during nicotine-withdrawal in mice.

PMID- 29042207
TI  - Nimodipine attenuates tau phosphorylation at Ser396 via miR-132/GSK-3beta pathway
      in chronic cerebral hypoperfusion rats.
AB  - Chronic cerebral hypofusion (CCH) promotes hyperphosphorylation of tau proteins,
      a key neuropathological trait that reflects neurodegenerative disorders.
      Nimodipine, an L-type calcium channel antagonist, has been reported to show
      neuroprotective effects. In this study, we investigated the potential mechanism
      of nimodipine in tauopathies induced by CCH. MiR-132 is downregulated in
      tauopathies such as AD and directly targets tau mRNA to regulate its expression.
      Here, we report that CCH induced miR-132 deficiency and increased tau
      phosphorylation at Ser396 while tau expression was not influenced. Nimodipine
      treatment attenuated CCH induced tau phosphorylation by up-regulating expression
      of miR-132. Furthermore, nimodipine inhibited activation of GSK-3beta and
      neuronal apoptosis induced by CCH. Interestingly, GSK-3betamRNA level negatively
      correlated with the expression of miR-132. These findings support a role for
      nimodipine inhibiting tau phosphorylation at Ser396 via miR-132/GSK-3beta.
      Therefore, nimodipine may be a candidate for the treatment of tauopathy present
      in CCH.

PMID- 29042208
TI  - Antiallodynic activity of leflunomide is partially inhibited by naltrexone and
      glibenclamide and associated with reduced production of TNF-alpha and CXCL-1.
AB  - Leflunomide, an immunosuppressive drug approved for the treatment of patients
      with rheumatoid arthritis, exhibits many mechanisms which may affect the
      nociceptive processing. Therefore, the present study aimed to evaluate the effect
      induced by leflunomide on the mechanical allodynia in models of inflammatory and
      neuropathic pain in mice and investigate mechanisms mediating such effects. Per
      os (p.o.) administration of leflunomide (25, 50 or 100mg/kg) inhibited the
      inflammatory edema and mechanical allodynia induced by intraplantar carrageenan.
      Even ongoing inflammatory edema and mechanical allodynia were reduced by
      leflunomide. Previous administration of naltrexone (10mg/kg, intraperitoneal) or
      glibenclamide (40mg/kg, p.o.) partially attenuated leflunomide antiallodynic
      activity. A single administration of leflunomide (50 or 100mg/kg, p.o.) also
      partially inhibited ongoing mechanical allodynia induced by chronic constriction
      injury (CCI) or repeated administrations of paclitaxel. The antiallodynic effect
      induced by leflunomide (50 or 100mg/kg, p.o.) in the model of neuropathic pain
      induced by CCI was associated with reduced production of tumor necrosis factor
      alpha both at the injury site and ipsilateral paw. Leflunomide also reduced
      production of the chemokine CXCL-1 at the paw ipsilateral to the injury site.
      Concluding, leflunomide partially inhibited ongoing mechanical allodynia in
      models of inflammatory and neuropathic pain. The antiallodynic effect was
      associated with activation of opioidergic receptors and ATP-sensitive potassium
      channels and reduced production of inflammatory mediators. These data indicate
      leflunomide as a drug that should be further investigated aiming to identify a
      new analgesic pharmacotherapy and reinforces repositioning as an important
      strategy to identify new uses for approved drugs.

PMID- 29042209
TI  - Chondrocytes damage induced by T-2 toxin via Wnt/beta-catenin signaling pathway
      is involved in the pathogenesis of an endemic osteochondropathy, Kashin-Beck
      disease.
AB  - Kashin-Beck disease (KBD), an endemic osteochondropathy, is characterized by
      cartilage degeneration which is caused by abnormal catabolism in the
      extracellular matrix (ECM). In this study, we investigated the expression of the
      Wnt/beta-catenin signaling pathway in KBD pathogenesis. Among the proteins
      involved in the Wnt/beta-catenin signaling pathway, WNT-3A, FZD1, SOX9, and beta
      catenin were up-regulated, while FRZB was down-regulated in KBD cartilage. C28/I2
      cells were evaluated for cell viability using the MTT assay after exposure to T-2
      toxin, a suspicious environmental pathogenic factors of KBD. C28/I2 cells were
      treated with different intervening concentrations (0.001MUg/mL,0.005MUg/mL and
      0.01MUg/mL) of T-2 toxin for 24h. The expression of FZD1 and CTNNB1 (i.e.,beta
      catenin) was significantly reduced and SOX9 expression was significantly
      increased in chondrocytes after treatment with different intervening
      concentrations of T-2 toxin. Our results indicate that alterations in the
      Wnt/beta-catenin signaling pathway in articular cartilage play an important role
      in the onset and pathogenesis of KBD.

PMID- 29042210
TI  - The Physicochemical Basis of Clofazimine-Induced Skin Pigmentation.
AB  - Clofazimine is a weakly basic, Food and Drug Administration-approved antibiotic
      recommended by the World Health Organization to treat leprosy and multi-drug
      resistant tuberculosis. Upon prolonged treatment, clofazimine extensively
      bioaccumulates and precipitates throughout the organism, forming crystal-like
      drug inclusions (CLDIs). Due to the drug's red color, it is widely believed that
      clofazimine bioaccumulation results in skin pigmentation, its most common side
      effect. To test whether clofazimine-induced skin pigmentation is due to CLDI
      formation, we synthesized a closely related clofazimine analog that does not
      precipitate under physiological pH and chloride conditions that are required for
      CLDI formation. Despite the absence of detectable CLDIs in mice, administration
      of this analog still led to significant skin pigmentation. In clofazimine-treated
      mice, skin cryosections revealed no evidence of CLDIs when analyzed with a
      microscopic imaging system specifically designed for detecting clofazimine
      aggregates. Rather, the reflectance spectra of the skin revealed a signal
      corresponding to the soluble, free base form of the drug. Consistent with the low
      concentrations of clofazimine in the skin, these results suggest that clofazimine
      induced skin pigmentation is not due to clofazimine precipitation and CLDI
      formation, but rather to the partitioning of the circulating, free base form of
      the drug into subcutaneous fat.

PMID- 29042211
TI  - A simple mathematical model of cell clustering by chemotaxis.
AB  - Chemotaxis is the process by which cells and clusters of cells follow chemical
      signals in order to combine and form larger clusters. The spreading of the
      chemical signal from any given cell can be modeled using the linear diffusion
      equation, and the standard equations of motion can be used to determine how a
      cell, or cluster of cells, moves in response to the chemical signal. The
      resulting differential equations for the cell locations are integrated through
      time using the fourth-order Runge-Kutta method. The effect which changing the
      initial concentration magnitude, diffusion constant and velocity damping
      parameter has on the shape of the final clusters of cells is investigated and
      discussed.

PMID- 29042212
TI  - MoRFPred-plus: Computational Identification of MoRFs in Protein Sequences using
      Physicochemical Properties and HMM profiles.
AB  - MOTIVATION: Intrinsically Disordered Proteins (IDPs) lack stable tertiary
      structure and they actively participate in performing various biological
      functions. These IDPs expose short binding regions called Molecular Recognition
      Features (MoRFs) that permit interaction with structured protein regions. Upon
      interaction they undergo a disorder-to-order transition as a result of which
      their functionality arises. Predicting these MoRFs in disordered protein
      sequences is a challenging task. METHOD: In this study, we present MoRFpred-plus,
      an improved predictor over our previous proposed predictor to identify MoRFs in
      disordered protein sequences. Two separate independent propensity scores are
      computed via incorporating physicochemical properties and HMM profiles, these
      scores are combined to predict final MoRF propensity score for a given residue.
      The first score reflects the characteristics of a query residue to be part of
      MoRF region based on the composition and similarity of assumed MoRF and flank
      regions. The second score reflects the characteristics of a query residue to be
      part of MoRF region based on the properties of flanks associated around the given
      residue in the query protein sequence. The propensity scores are processed and
      common averaging is applied to generate the final prediction score of MoRFpred
      plus. RESULTS: Performance of the proposed predictor is compared with available
      MoRF predictors, MoRFchibi, MoRFpred, and ANCHOR. Using previously collected
      training and test sets used to evaluate the mentioned predictors, the proposed
      predictor outperforms these predictors and generates lower false positive rate.
      In addition, MoRFpred-plus is a downloadable predictor, which makes it useful as
      it can be used as input to other computational tools. AVAILABILITY:
      https://github.com/roneshsharma/MoRFpred-plus/wiki/MoRFpred-plus:-Download.

PMID- 29042213
TI  - Morpho-functional variety of the coxal glands in cheyletoid mites (Prostigmata).
      II. Cheyletidae.
AB  - Trombidiform mites are characterized by the presence of several paired glands in
      the anterior body portion united by a common conducting duct (podocephalic
      canal). Apart from the acinous (salivary) glands the podocephalic system includes
      a pair of tubular coxal glands (CGs) responsible for osmoregulation. The aim of
      the present study was to figure out how functional changes of acinous glands
      reflect on the corresponding CG. For this purpose, the anatomy and fine structure
      of the CG were analyzed in two mite species, Bakericheyla chanayi and
      Ornithocheyletia sp. (Cheyletidae), which have a different composition of their
      single acinous gland. The results showed that in both species the CG lacks a
      filtering saccule. It is composed of the proximal and distal tubes and leads into
      a cuticle-lined excretory duct. Both tubes demonstrate a similar species-specific
      fine structure. They are characterized by an extensive system of apical membrane
      invaginations (internal canals) associated with numerous large mitochondria.
      Local areas of modified internal canals were regularly observed in both species.
      They contain structures resembling those constituting filtering slit diaphragms
      of other animals. In O. sp., CG cells in addition demonstrate features
      characteristic of protein-like secretion. Apparently this correlates with the
      loss of true salivary glands in this species, as its acinous gland was previously
      assumed as silk producing. Contrary to this, the CG of B. chanayi shows no kind
      of granulation, which coincides with the presence of a salivary portion in its
      complex acinous gland. The microtubule-rich intercalary cells at the base of the
      excretory duct were associated with special muscles presumably regulating the
      dilation of the duct lumen. These cells might represent a basic feature common to
      different types of podocephalic glands.

PMID- 29042214
TI  - Synthetic cannabinoid AM2201 induces seizures: Involvement of cannabinoid CB1
      receptors and glutamatergic transmission.
AB  - Abuse of synthetic cannabinoids is a serious social problem worldwide.
      Intentional ingestion of synthetic cannabinoids can cause severe toxicity,
      including seizures. Here we investigated the effects of acute administration of
      synthetic cannabinoids on the induction of epileptic seizures by monitoring
      electroencephalographic activity in freely moving mice. The synthetic
      cannabinoid, AM2201, induced abnormal, high-amplitude (>2-fold baseline
      amplitude), sharp-wave activity. The abnormal spike-wave discharges were
      accompanied by epileptiform behavior: rigid posture, tail extension, rearing with
      forepaws extended, jumping, and intermittent tonic-clonic jerking movements. The
      abnormal spike-wave discharges and behavioral changes were suppressed by
      pretreatment with the selective CB1 receptor antagonist AM251, but not with the
      selective CB2 receptor antagonist AM630 or the vanilloid receptor antagonist,
      capsazepine. Furthermore, the group 1 metabotropic glutamate receptor antagonist
      SIB1757 eliminated AM2201-induced spike-wave discharges and episodes of
      epileptiform behavior. AM2201 markedly increased the extracellular glutamate
      concentration in the hippocampus during periods of AM2201-induced abnormal spike
      wave discharges and behavioral changes. These findings are the first evidence
      that AM2201 induces epileptic seizures by enhancing glutamatergic transmission in
      the hippocampus. Our findings demonstrate that induction of epileptic seizures by
      synthetic cannabinoids is mediated by CB1 receptors, but not by CB2 receptors,
      and further suggest that rapid elevation of glutamatergic transmission may play
      an important role in the induction of seizures following intentional ingestion of
      synthetic cannabinoids.

PMID- 29042215
TI  - A novel stilbene-like compound that inhibits melanoma growth by regulating
      melanocyte differentiation and proliferation.
AB  - Melanoma is the most aggressive form of skin cancer. Current challenges to
      melanoma therapy include the adverse effects from immunobiologics, resistance to
      drugs targeting the MAPK pathway, intricate interaction of many signal pathways,
      and cancer heterogeneity. Thus combinational therapy with drugs targeting
      multiple signaling pathways becomes a new promising therapy. Here, we report a
      family of stilbene-like compounds called A11 that can inhibit melanoma growth in
      both melanoma-forming zebrafish embryos and mouse melanoma cells. The growth
      inhibition by A11 is a result of mitosis reduction but not apoptosis enhancement.
      Meanwhile, A11 activates both MAPK and Akt signaling pathways. Many A11-treated
      mouse melanoma cells exhibit morphological changes and resemble normal
      melanocytes. Furthermore, we found that A11 causes down-regulation of melanocyte
      differentiation genes, including Pax3 and MITF. Together, our results suggest
      that A11 could be a new melanoma therapeutic agent by inhibiting melanocyte
      differentiation and proliferation.

PMID- 29042217
TI  - The detection of hepatitis c virus core antigen using afm chips with immobolized
      aptamers.
AB  - In the present study, the possibility of hepatitis C virus core antigen
      (HCVcoreAg) detection in buffer solution, using atomic force microscope chip (AFM
      chip) with immobilized aptamers, has been demonstrated. The target protein was
      detected in 1mL of solution at concentrations from 10-10M to 10-13M. The
      registration of aptamer/antigen complexes on the chip surface was carried out by
      atomic force microscopy (AFM). The further mass-spectrometric (MS) identification
      of AFM-registered objects on the chip surface allowed reliable identification of
      HCVcoreAg target protein in the complexes. Aptamers, which were designed for
      therapeutic purposes, have been shown to be effective in HCVcoreAg detection as
      probe molecules.

PMID- 29042218
TI  - Interest of proviral HIV-1 DNA genotypic resistance testing in virologically
      suppressed patients candidate for maintenance therapy.
AB  - Switch of antiretroviral therapy in virologically suppressed HIV-infected
      patients is frequent, to prevent toxicities, for simplification or convenience
      reasons. Pretherapeutic genotypic resistance testing on RNA can be lacking in
      some patients, which could enhance the risk of virologic failure, if resistance
      associated mutations of the new regimen are not taken into account. Proviral DNA
      resistance testing in 69 virologically suppressed patients on antiretroviral
      treatment with no history of virological failure were pair-wised compared with
      pre-ART plasma RNA resistance testing. The median time between plasma (RNA
      testing) and whole blood (proviral DNA testing) was 47 months (IQR 29-63). A stop
      codon was evidenced in 23% (16/69) of proviral DNA sequences; these strains were
      considered as defective, non-replicative, and not taken into consideration.
      Within the non defective strains, concordance rate between plasma RNA and non
      defective proviral DNA was high both on protease (194/220 concordant resistance
      associated mutations=88%) and reverse transcriptase (28/37 concordant resistance
      associated mutations=76%) genes. This study supports that proviral DNA testing
      might be an informative tool before switching antiretrovirals in virologically
      suppressed patients with no history of virological failure, but the
      interpretation should be restricted to non-defective viruses.

PMID- 29042216
TI  - Mapping human brain lesions and their functional consequences.
AB  - Neuroscience has a long history of inferring brain function by examining the
      relationship between brain injury and subsequent behavioral impairments. The
      primary advantage of this method over correlative methods is that it can tell us
      if a certain brain region is necessary for a given cognitive function. In
      addition, lesion-based analyses provide unique insights into clinical deficits.
      In the last decade, statistical voxel-based lesion behavior mapping (VLBM)
      emerged as a powerful method for understanding the architecture of the human
      brain. This review illustrates how VLBM improves our knowledge of functional
      brain architecture, as well as how it is inherently limited by its mass
      univariate approach. A wide array of recently developed methods appear to
      supplement traditional VLBM. This paper provides an overview of these new
      methods, including the use of specialized imaging modalities, the combination of
      structural imaging with normative connectome data, as well as multivariate
      analyses of structural imaging data. We see these new methods as complementing
      rather than replacing traditional VLBM, providing synergistic tools to answer
      related questions. Finally, we discuss the potential for these methods to become
      established in cognitive neuroscience and in clinical applications.

PMID- 29042219
TI  - Accurate Classification of Diminutive Colorectal Polyps Using Computer-Aided
      Analysis.
AB  - BACKGROUND & AIMS: Narrow-band imaging is an image-enhanced form of endoscopy
      used to observed microstructures and capillaries of the mucosal epithelium which
      allows for real-time prediction of histologic features of colorectal polyps.
      However, narrow-band imaging expertise is required to differentiate hyperplastic
      from neoplastic polyps with high levels of accuracy. We developed and tested a
      system of computer-aided diagnosis with a deep neural network (DNN-CAD) to
      analyze narrow-band images of diminutive colorectal polyps. METHODS: We collected
      1476 images of neoplastic polyps and 681 images of hyperplastic polyps, obtained
      from the picture archiving and communications system database in a tertiary
      hospital in Taiwan. Histologic findings from the polyps were also collected and
      used as the reference standard. The images and data were used to train the DNN. A
      test set of images (96 hyperplastic and 188 neoplastic polyps, smaller than 5
      mm), obtained from patients who underwent colonoscopies from March 2017 through
      August 2017, was then used to test the diagnostic ability of the DNN-CAD vs
      endoscopists (2 expert and 4 novice), who were asked to classify the images of
      the test set as neoplastic or hyperplastic. Their classifications were compared
      with findings from histologic analysis. The primary outcome measures were
      diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV),
      negative predictive value (NPV), and diagnostic time. The accuracy, sensitivity,
      specificity, PPV, NPV, and diagnostic time were compared among DNN-CAD, the
      novice endoscopists, and the expert endoscopists. The study was designed to
      detect a difference of 10% in accuracy by a 2-sided McNemar test. RESULTS: In the
      test set, the DNN-CAD identified neoplastic or hyperplastic polyps with 96.3%
      sensitivity, 78.1% specificity, a PPV of 89.6%, and a NPV of 91.5%. Fewer than
      half of the novice endoscopists classified polyps with a NPV of 90% (their NPVs
      ranged from 73.9% to 84.0%). DNN-CAD classified polyps as neoplastic or
      hyperplastic in 0.45 +/- 0.07 seconds-shorter than the time required by experts
      (1.54 +/- 1.30 seconds) and nonexperts (1.77 +/- 1.37 seconds) (both P < .001).
      DNN-CAD classified polyps with perfect intra-observer agreement (kappa score of
      1). There was a low level of intra-observer and inter-observer agreement in
      classification among endoscopists. CONCLUSIONS: We developed a system called DNN
      CAD to identify neoplastic or hyperplastic colorectal polyps less than 5 mm. The
      system classified polyps with a PPV of 89.6%, and a NPV of 91.5%, and in a
      shorter time than endoscopists. This deep-learning model has potential for not
      only endoscopic image recognition but for other forms of medical image analysis,
      including sonography, computed tomography, and magnetic resonance images.

PMID- 29042221
TI  - Development of photoaffinity derivatives of the antitumor macrolide aplyronine A,
      a PPI-inducer between actin and tubulin.
AB  - The antitumor and actin-depolymerizing marine macrolide aplyronine A (ApA)
      synergistically binds to tubulin in association with actin, and prevents spindle
      formation and mitosis. While the crystal structure of the actin ApA complex was
      solved in 2006, its interaction with the tubulin heterodimer has not been
      clarified. To investigate the binding modes of ApA as a unique protein-protein
      interaction (PPI)-inducer between these two cytoskeletal proteins, we prepared
      its photoaffinity acetylene and fluorescent derivatives with the aid of molecular
      modeling studies for probe design. Among these three derivatives, the ApA-PPA
      TAMRA probe specifically photoreacted with both actin and tubulin in vitro.
      However, the photolabeling yield of tubulin was quite low (up to ~1%), and one of
      the major side-reactions was the addition of a water molecule to the carbene
      species generated from an aryldiazirine moiety on the hydrophilic surface of
      actin.

PMID- 29042220
TI  - Long Noncoding RNA uc.173 Promotes Renewal of the Intestinal Mucosa by Inducing
      Degradation of MicroRNA 195.
AB  - BACKGROUND AND AIMS: The mammalian intestinal epithelium self-renews rapidly and
      homeostasis is preserved via tightly controlled mechanisms. Long noncoding RNAs
      transcribed from ultraconserved regions (T-UCRs) control different cell
      functions, but little is known about their role in maintaining the integrity of
      the intestinal epithelium. We searched for T-UCRs that regulate growth of the
      intestinal mucosa and investigated the mechanism by which T-UCR uc.173 regulates
      epithelial renewal. METHODS: C57BL/6J mice were deprived of food for 48 hours in
      fasting experiments. Some mice were given intraperitoneal injections of a plasmid
      encoding LNA-anti-uc.173, to knock down endogenous uc.173. For studies using
      organoids, primary enterocytes were isolated from the intestine and transfected
      with the uc.173 transgene to increase uc.173 levels. Intestinal epithelial cells
      (Caco-2 and IEC-6 lines) were transfected with LNA-anti-uc.173 or uc.173
      transgene. We quantified intestinal epithelial renewal based on BrdU
      incorporation, villus height and crypt depth, and cell number. The association of
      uc.173 with microRNA 195 (miRNA195) was determined by RNA pull-down assays.
      RESULTS: Genome-wide profile analyses identified 21 T-UCRs, including uc.173,
      that were differentially expressed between intestinal mucosa of fasted vs non
      fasted mice. Increasing levels of uc.173 by expression of a transgene increased
      growth of intestinal epithelial cells and organoids. Decreasing uc.173 levels by
      LNA-anti-uc.173 in mice reduced renewal of the intestinal epithelium. We found
      that uc.173 interacted directly with the primary transcript of miRNA195, leading
      to miRNA195 degradation. CONCLUSIONS: In analyses of intestinal epithelial cells
      and mice, we identified uc.173 noncoding RNA that regulates growth of the
      intestinal mucosa and stimulates intestinal epithelial renewal by reducing levels
      of miRNA195.

PMID- 29042222
TI  - Development of a microarray-based assay for efficient testing of new HSP70/DnaK
      inhibitors.
AB  - A facile method for testing ATP binding in a highly miniaturized microarray
      environment using human HSP70 and DnaK from Mycobacterium tuberculosis as
      biological targets is reported. Supported by molecular modelling studies we
      demonstrate that the position of the fluorescence label on ATP has a strong
      influence on the binding to human HSP70. Importantly, the label has to be
      positioned on the adenine ring and not to the terminal phosphate group.
      Unlabelled ATP displaced bound Cy5-ATP from HSP70 in the micromolar range. The
      affinity of a well-known HSP70 inhibitor VER155008 for the ATP binding site in
      HSP70 was determined, with a EC50 in the micromolar range, whereas reblastin, a
      HSP90-inhibitor, did not compete for ATP in the presence of HSP70. The
      applicability of the method was demonstrated by screening a small compound
      library of natural products. This unraveled that terphenyls rickenyl A and D,
      recently isolated from cultures of the fungus Hypoxylon rickii, are inhibitors of
      HSP70. They compete with ATP for the chaperone in the range of 29 uM (Rickenyl D)
      and 49 uM (Rickenyl A). Furthermore, the microarray-based test system enabled
      protein-protein interaction analysis using full-length HSP70 and HSP90 proteins.
      The labelled full-length human HSP90 binds with a half-maximal affinity of 5.5
      ug/ml (~40 uM) to HSP70. The data also demonstrate that the microarray test has
      potency for many applications from inhibitor screening to target-oriented
      interaction studies.

PMID- 29042223
TI  - Astemizole analogues with reduced hERG inhibition as potent antimalarial
      compounds.
AB  - Astemizole is a H1-antagonist endowed with antimalarial activity, but has hERG
      liabilities. Systematic structural modifications of astemizole led to the
      discovery of analogues that display very potent activity as inhibitors of the
      growth of the Plasmodium parasite, but show a decreased hERG inhibition, when
      compared to astemizole. These compounds can be used as starting point for the
      development of a new class of antimalarials.

PMID- 29042224
TI  - Potent anti-melanogenic activity and favorable toxicity profile of selected 4
      phenyl hydroxycoumarins in the zebrafish model and the computational molecular
      modeling studies.
AB  - 7-Hydroxy-4-phenylcoumarin (7C) and 5,7-dihydroxy-4-phenylcoumarin (5,7C) have
      been evaluated as potential anti-melanogenic agents in the zebrafish (Danio
      rerio) model in comparison to commercially utilized depigmenting agents
      hydroquinone and kojic acid. 7C and 5,7C decreased the body pigmentation at 5
      ug/mL, while did not affect the embryos development and survival at doses <=50
      ug/mL and <=25 ug/mL. Unlike hydroquinone and kojic acid, 4-phenyl
      hydroxycoumarins were no melanocytotoxic, showed no cardiotoxic side effects,
      neither caused neutropenia in zebrafish embryos, suggesting these compounds may
      present novel skin-whitening agents with improved pharmacological properties.
      Inhibition of tyrosinase was identified as the possible mode of anti-melanogenic
      action. Molecular docking studies using the homology model of human tyrosinase as
      well as adenylate cyclase revealed excellent correlation with experimentally
      obtained results.

PMID- 29042225
TI  - Peptides for optical medical imaging and steps towards therapy.
AB  - Optical medical imaging is a rapidly growing area of research and development
      that offers a multitude of healthcare solutions both diagnostically and
      therapeutically. In this review, some of the most recently described peptide
      based optical probes are reviewed with a special emphasis on their in vivo use
      and potential application in a clinical setting.

PMID- 29042226
TI  - Liquid nitrogen cryotherapy for chronic recalcitrant interdigital candidiasis of
      toe spaces-an uncontrolled pilot study.

PMID- 29042227
TI  - Pathogenetic insights from quantification of the cerebriform connective tissue
      nevus in Proteus syndrome.
AB  - BACKGROUND: The plantar cerebriform connective tissue nevus (CCTN) is the most
      common and problematic cutaneous manifestation of Proteus syndrome. OBJECTIVE: To
      gain insights into CCTN pathogenesis and natural history. METHODS: The size and
      location of plantar CCTN was measured on 152 images from 22 individuals with
      Proteus syndrome by 2 independent, blinded reviewers. Average measures of plantar
      CCTN were transformed into a linear mixed model to estimate proportionate change
      in size with age. RESULTS: Median patient age was 6.9 years at study onset. The
      intraclass correlation coefficient between 2 blinded reviewers was 0.946 for CCTN
      single measures. The CCTN relative area increased with age in children (n = 18, P
      < .0001) by 5.6% per year. Confluent papules and nodules extending beyond the
      boundaries of CCTNs were gradually replaced by typical CCTN over time. The
      location of CCTN in different individuals overlapped near the ball of the foot. A
      positive relationship between CCTN growth rate and AKT1 mutant allele frequency
      was observed (0.62, P = .10, n = 8). LIMITATIONS: This was a retrospective review
      using photographs. CONCLUSION: CCTN growth is affected by age and extent of the
      CCTN precursor lesion. Monitoring of CCTN size might prove useful for evaluating
      drug response in the treatment of Proteus syndrome.

PMID- 29042228
TI  - Beyond the triad: Inheritance, mucocutaneous phenotype, and mortality in a cohort
      of patients with dyskeratosis congenita.

PMID- 29042229
TI  - Allergen of the Year alkyl glucoside is an ingredient in top-selling sunscreens
      and facial moisturizers.

PMID- 29042230
TI  - Risk of melanoma in patients with multiple myeloma: A Surveillance, Epidemiology,
      and End Results population-based study.

PMID- 29042231
TI  - Commentary: The Corrona-National Psoriasis Foundation Psoriasis Registry: A new
      collaborative approach for postapproval registries.

PMID- 29042232
TI  - Gender Differences in Indoor Tanning Habits and Location.

PMID- 29042233
TI  - Trends in device utilization ratios in intensive care units over 10-year period
      in South Korea: device utilization ratio as a new aspect of surveillance.
AB  - BACKGROUND: Device-associated infection (DAI) is an important issue related to
      patient safety. It is important to reduce unnecessary device utilization in order
      to decrease DAI rates. AIM: To investigate the time trend of device utilization
      ratios (DURs) of voluntarily participating hospitals, collected over a 10-year
      period through the Korean National Healthcare-associated Infections Surveillance
      System (KONIS). METHODS: DURs from 2006 to 2015 in 190 intensive care units
      (ICUs) participating in KONIS were included in this study. DURs were calculated
      as the ratio of device-days to patient-days. The pooled incidences of DAIs and
      DURs were calculated for each year of participation, and the year-wise trends
      were analysed. FINDINGS: Year-wise ventilator utilization ratio (V-DUR) increased
      significantly from 0.40 to 0.41 (F = 6.27, P < 0.01), urinary catheter
      utilization ratio (U-DUR) increased non-significantly from 0.83 to 0.84 (F =
      1.66, P = 0.10), and C-line utilization ratio (CL-DUR) decreased non
      significantly from 0.55 to 0.51 (F = 1.62, P = 0.11). In the subgroup analysis,
      'medical ICU' (F = 2.79, P < 0.01) and 'hospital with >900 beds' (F = 3.07, P <
      0.01) were associated with the significant increase in V-DUR. CONCLUSION: In
      Korea, V-DUR showed a significant, year-wise increasing trend. The trends for U
      DUR and CL-DUR showed no significant decrease. Efforts are required to ensure the
      reduction of DURs.

PMID- 29042234
TI  - Mother-to-child transmission of KPC-producing Klebsiella pneumoniae: potential
      relevance of a low microbial urinary load for screening purposes.

PMID- 29042235
TI  - Splicing factors as regulators of miRNA biogenesis - links to human disease.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post
      transcriptionally by fine-tuning mRNA levels and translation during development
      and in adult tissues. miRNAs are transcribed as parts of longer precursors that
      undergo multiple processing steps before the mature miRNAs reach their target
      mRNAs in the cytoplasm. In addition to Drosha/DGCR8 and Dicer that are the
      essential components of the miRNA processing pathway, a range of other RNA
      binding proteins have recently been implicated in miRNA biogenesis. Among these,
      several well-known splicing factors have emerged as regulators of distinct
      miRNAs. In this review, we examine the mechanisms by which splicing factors
      regulate miRNA biogenesis. As both splicing factors and miRNAs play central roles
      in human disease biology we discuss implications of the links between splicing
      factors and miRNAs in human disease.

PMID- 29042236
TI  - Mass spectrometry approaches to study plant endomembrane trafficking.
AB  - Intracellular proteins reside in highly controlled microenvironments in which
      they perform context specific functions. Trafficking pathways have evolved that
      enable proteins to be precisely delivered to the correct location but also to re
      locate in response to environmental perturbation. Trafficking of membrane
      proteins to their correct endomembrane location is especially important to enable
      them to carry out their function. Although a considerable amount of knowledge
      about membrane protein trafficking in plants has been delivered by years of
      dedicated research, there are still significant gaps in our understanding of this
      process. Further knowledge of endomembrane trafficking is dependent on thorough
      characterization of the subcellular components that constitute the endomembrane
      system. Such studies are challenging for a number of reasons including the
      complexity of the plant endomembrane system, inability to purify individual
      constituents, discrimination protein cargo for full time residents of
      compartments, and the fact that many proteins function at more than one location.
      In this review, we describe the components of the secretory pathway and focus on
      how mass spectrometry based proteomics methods have helped elucidation of this
      pathway. We demonstrate that the combination of targeted and untargeted
      approaches is allowing research into new areas of the secretory pathway
      investigation. Finally we describe new enabling technologies that will impact
      future studies in this area.

PMID- 29042237
TI  - Ligand partitioning into lipid bilayer membranes under high pressure: Implication
      of variation in phase-transition temperatures.
AB  - The variation in phase-transition temperatures of dipalmitoylphosphatidylcholine
      (DPPC) bilayer membrane by adding two membrane-active ligands, a long-chain fatty
      acid (palmitic acid (PA)) and an inhalation anesthetic (halothane (HAL)), was
      investigated by light-transmittance measurements and fluorometry. By assuming the
      thermodynamic colligative property for the bilayer membrane at low ligand
      concentrations, the partitioning behavior of these ligands into the DPPC bilayer
      membrane was considered. It was proved from the differential partition
      coefficients between two phases that PA has strong affinity with the gel
      (lamellar gel) phase in a micro-molal concentration range and makes the bilayer
      membrane more ordered, while HAL has strong affinity with the liquid crystalline
      phase in a milli-molal concentration range and does the bilayer membrane more
      disordered. The transfer volumes of both ligands from the aqueous solution to
      each phase of the DPPC bilayer membrane showed that the preferential partitioning
      of the PA molecule into the gel (lamellar gel) produces about 20% decrease in
      transfer volume as compared with the liquid crystalline phase, whereas that of
      the HAL molecule into the liquid crystalline phase does about twice increase in
      transfer volume as compared with the gel (ripple gel) phase. Furthermore, changes
      in thermotropic and barotropic phase behavior of the DPPC bilayer membrane by
      adding the ligand was discussed from the viewpoint of the ligand partitioning.
      Reflecting the contrastive partitioning of PA and HAL into the pressure-induced
      interdigitated gel phase among the gel phases, it was revealed that PA suppresses
      the formation of the interdigitated gel phase under high pressure while HAL
      promotes it. These results clearly indicate that each phase of the DPPC bilayer
      membrane has a potential to recognize various ligand molecules.

PMID- 29042238
TI  - Novel strategy for immunomodulation: Dissolving microneedle array encapsulating
      thymopentin fabricated by modified two-step molding technology.
AB  - Thymopentin (TP5) is commonly used in the treatment for autoimmune diseases, with
      a short plasma half-life (30s) and a long treatment period (7 days to 6 months).
      It is usually administrated by syringe injection, resulting in compromised
      patient compliance. Dissolving microneedle array (DMNA) offers a superior
      approach for transdermal delivery of biological macromolecules, as it allows
      painless penetration through the stratum corneum and generates minimal
      biohazardous waste after dissolving in the skin. Despite recent advances in DMNA
      as a novel approach for transdermal drug delivery, problem of insufficient
      mechanical strength remains to be solved. In this study, TP5-loaded DMNA (TP5
      DMNA) was uniquely developed using a modified two-step molding technology. The
      higher mechanical strength was furnished by employing bovine serum albumin (BSA)
      as a co-material to fabricate the needles. The obtained TP5-DMNA containing BSA
      displayed better skin penetration and higher drug loading efficiency than that
      without BSA. The in vivo pharmacodynamics study demonstrated that TP5-DMNA had
      comparative effect on immunomodulation to intravenous injection of TP5, in terms
      of ameliorating the CD4+/CD8+ ratio, SOD activity and MDA value to the basal
      level. Only mild irritation was observed at the site of administration. These
      results suggest that the novel TP5-DMNA utilizing BSA provides an alternative
      approach for convenient and safe transdermal delivery of TP5, which is a
      promising administration strategy for future clinical application.

PMID- 29042239
TI  - Microbiota of field-collected Ixodes scapularis and Dermacentor variabilis from
      eastern and southern Ontario, Canada.
AB  - The microbiota of hard ticks has been an area of growing interest due to the
      potential role that the broader microbial community may play in pathogen carriage
      and transmission. In the last two decades, Ontario, Canada has experienced rapid
      changes in the risk of tick-borne disease, primarily due to the range expansion
      of Ixodes scapularis. Another human-biter, Dermacentor variabilis, is a
      longstanding resident of the province, but currently poses minimal risk of
      pathogen transmission. To examine the microbiota of these two species, we
      collected adult and nymphal I. scapularis and D. variabilis from the eastern and
      southern regions of the province via tick dragging, and conducted next generation
      sequencing of 19 samples (composed of 45 ticks) via Illumina MiSeq. A total of
      1400469 sequences were detected (median 69118/sample; range 23350-155227). The
      most abundant families of bacteria were unclassified Clostridiales and
      Ruminococcaceae for both I. scapularis and D. variabilis. No significant
      differences in the relative abundances of any phylum, class, order, family or
      genus were detected between locations (east vs south), sex, life stage or tick
      species. There were no differences in community membership or structure based on
      unifrac and AMOVA analyses. Female and male ticks had lower microbial diversity
      when compared to nymphs, based on the Simpson's index and Shannon evenness index.
      The findings of our study differ from previous studies of these tick species
      conducted in other geographic areas, and highlight the potential role geography
      and related ecological factors may have in shaping the tick microbiota.

PMID- 29042240
TI  - Coxiella burnetii and Rickettsia conorii: Two zoonotic pathogens in peridomestic
      rodents and their ectoparasites in Nigeria.
AB  - Rodents are hosts of numerous pathogenic agents of public health importance
      globally. Their ability to harbor these pathogens without showing overt clinical
      signs of disease has epidemiologic consequences. In some rural settings in
      Nigeria, humans and rodents do not only share feeds and abode, but the latter may
      end up on the table of the former as a source of protein, thereby increasing the
      risks of disease transmission. Molecular assays were used to detect and
      characterize two agents of zoonotic importance, Coxiella burnetii and Rickettsia
      spp. in 194 peridomestic rodents captured in a peri-urban setting in Nigeria, and
      32 pools of ectoparasites removed from them, to determine their possible role in
      the epidemiology of these diseases in this country. Targeting and characterizing
      the insertion sequence IS1111, C. burnetii DNA was detected in 4 out of 194
      (2.1%) rodents comprising 3 out of 121 (2.5%) Rattus norvegicus and 1 out of 48
      (2.1%) Rattus rattus screened in this study. Rickettsia spp. DNA was detected in
      two Rhipicephalus sanginueus sensu lato pools (i.e. RT1 and RT4) using the
      citrate synthase (gltA) gene and further characterized by amplification and
      sequence analysis of six genes to determine their identity. The RT1 sample
      consistently gave 98-100% identity to Rickettsia conorii str. Malish 7 for the
      various genes and loci studied. However, the identity of RT4 could not be
      definitively determined due to variable identities to different Rickettsia spp.
      according to the gene or loci under consideration. Further isolation study to
      determine if the RT4 characterized is a new variant or a mixture of sequences of
      different rickettsiae within the pool will be worthwhile.

PMID- 29042241
TI  - Randomized clinical study of wear of enamel antagonists against polished
      monolithic zirconia crowns.
AB  - OBJECTIVES: To test the hypothesis that there is no difference in the in vivo
      maximum wear of enamel opposing monolithic zirconia crowns, enamel opposing
      porcelain fused to metal crowns and enamel opposing enamel. METHODS: Thirty
      patients needing single crowns were randomized to receive either a monolithic
      zirconia or metal-ceramic crown. Two non-restored opposing teeth in the same
      quadrants were identified to serve as enamel controls. After cementation,
      quadrants were scanned for baseline data. Polyvinylsiloxane impressions were
      obtained and poured in white stone. Patients were recalled at six-months and one
      year for re-impression. Stone models were scanned using a tabletop laserscanner
      to determine maximum wear. Statistical analysis was performed using Mann-Whitney
      U to determine any significant differences between the wear of enamel against
      zirconia and metal-ceramic crowns. RESULTS: Sixteen zirconia and 14 metal-ceramic
      crowns were delivered. There were no statistical differences in mean wear of
      crown types (p=0.165); enamel antagonists (p=0.235) and enamel controls (p=0.843)
      after one year. CONCLUSION: Monolithic zirconia exhibited comparable wear of
      enamel compared with metal-ceramic crowns and control enamel after one year.
      SIGNIFICANCE: This study is clinically significant because the use of polished
      monolithic zirconia demonstrated comparable wear of opposing enamel to metal
      ceramic and enamel antagonists.

PMID- 29042242
TI  - Online Raman spectroscopy for structural biology on beamline ID29 of the ESRF.
AB  - Raman spectroscopy can probe the structure and conformations of specific chemical
      groups within proteins and may thus be used as a technique complementary to X-ray
      crystallography. This combined approach can be decisive in resolving ambiguities
      in the interpretation of enzymatic or X-ray induced processes. Here, we present
      an online Raman setup developed at the European Synchrotron that allows for
      interleaved Raman spectra acquisition and X-ray diffraction measurements with
      fast probe exchange and simple alignment while maintaining a high sensitivity
      over the entire spectral range. This device has been recently employed in the
      study of a covalent intermediate in the O2-dependent breakdown of uric acid by
      the cofactor-free enzyme urate oxidase and to monitor its decay induced by X-ray
      exposure.

PMID- 29042243
TI  - Extracellular self-DNA as a damage-associated molecular pattern (DAMP) that
      triggers self-specific immunity induction in plants.
AB  - Mammals sense self or non-self extracellular or extranuclear DNA fragments
      (hereinafter collectively termed eDNA) as indicators of injury or infection and
      respond with immunity. We hypothesised that eDNA acts as a damage-associated
      molecular pattern (DAMP) also in plants and that it contributes to self versus
      non-self discrimination. Treating plants and suspension-cultured cells of common
      bean (Phaseolus vulgaris) with fragmented self eDNA (obtained from other plants
      of the same species) induced early, immunity-related signalling responses such as
      H2O2 generation and MAPK activation, decreased the infection by a bacterial
      pathogen (Pseudomonas syringae) and increased an indirect defence to herbivores
      (extrafloral nectar secretion). By contrast, non-self DNA (obtained from lima
      bean, Phaseolus lunatus, and Acacia farnesiana) had significantly lower or no
      detectable effects. Only fragments below a size of 700 bp were active, and
      treating the eDNA preparation DNAse abolished its inducing effects, whereas
      treatment with RNAse or proteinase had no detectable effect. These findings
      indicate that DNA fragments, rather than small RNAs, single nucleotides or
      proteins, accounted for the observed effects. We suggest that eDNA functions a
      DAMP in plants and that plants discriminate self from non-self at a species
      specific level. The immune systems of plants and mammals share multiple central
      elements, but further work will be required to understand the mechanisms and the
      selective benefits of an immunity response that is triggered by eDNA in a species
      specific manner.

PMID- 29042244
TI  - Selectivity of coronaridine congeners at nicotinic acetylcholine receptors and
      inhibitory activity on mouse medial habenula.
AB  - The inhibitory activity of coronaridine congeners on human (h) alpha4beta2 and
      alpha7 nicotinic acetylcholine receptors (AChRs) is determined by Ca2+ influx
      assays, whereas their effects on neurons in the ventral inferior (VI) aspect of
      the mouse medial habenula (MHb) are determined by patch-clamp recordings. The
      Ca2+ influx results clearly establish that coronaridine congeners inhibit
      halpha3beta4 AChRs with higher selectivity compared to halpha4beta2 and halpha7
      subtypes, and with the following potency sequence, for halpha4beta2: (+/-)-18
      methoxycoronaridine [(+/-)-18-MC]>(+)-catharanthine>(+/-)-18
      methylaminocoronaridine [(+/-)-18-MAC] ~ (+/-)-18-hydroxycoronaridine [(+/-)-18
      HC]; and for halpha7: (+)-catharanthine>(+/-)-18-MC>(+/-)-18-HC>(+/-)-18-MAC.
      Interestingly, the inhibitory potency of (+)-catharanthine (27+/-4MUM) and (+/-)
      18-MC (28+/-6MUM) on MHb (VI) neurons was lower than that observed on
      halpha3beta4 AChRs, suggesting that these compounds inhibit a variety of
      endogenous alpha3beta4* AChRs. In addition, the interaction of bupropion with (-)
      ibogaine sites on halpha3beta4 AChRs is tested by [3H]ibogaine competition
      binding experiments. The results indicate that bupropion binds to ibogaine sites
      at desensitized halpha3beta4 AChRs with 2-fold higher affinity than at resting
      receptors, suggesting that these compounds share the same binding sites. In
      conclusion, coronaridine congeners inhibit halpha3beta4 AChRs with higher
      selectivity compared to other AChRs, by interacting with the bupropion (luminal)
      site. Coronaridine congeners also inhibit alpha3beta4*AChRs expressed in MHb (VI)
      neurons, supporting the notion that these receptors are important endogenous
      targets for their anti-addictive activities.

PMID- 29042245
TI  - A natural language processing challenge for clinical records: Research Domains
      Criteria (RDoC) for psychiatry.

PMID- 29042246
TI  - Probabilistic broken-stick model: A regression algorithm for irregularly sampled
      data with application to eGFR.
AB  - In order for clinicians to manage disease progression and make effective
      decisions about drug dosage, treatment regimens or scheduling follow up
      appointments, it is necessary to be able to identify both short and long-term
      trends in repeated biomedical measurements. However, this is complicated by the
      fact that these measurements are irregularly sampled and influenced by both
      genuine physiological changes and external factors. In their current forms,
      existing regression algorithms often do not fulfil all of a clinician's
      requirements for identifying short-term (acute) events while still being able to
      identify long-term, chronic, trends in disease progression. Therefore, in order
      to balance both short term interpretability and long term flexibility, an
      extension to broken-stick regression models is proposed in order to make them
      more suitable for modelling clinical time series. The proposed probabilistic
      broken-stick model can robustly estimate both short-term and long-term trends
      simultaneously, while also accommodating the unequal length and irregularly
      sampled nature of clinical time series. Moreover, since the model is parametric
      and completely generative, its first derivative provides a long-term non-linear
      estimate of the annual rate of change in the measurements more reliably than
      linear regression. The benefits of the proposed model are illustrated using
      estimated glomerular filtration rate as a case study used to manage patients with
      chronic kidney disease.

PMID- 29042247
TI  - Murine genetic variance in muscarinic cholinergic receptor antagonism of sucrose
      and saccharin solution intakes in three inbred mouse strains.
AB  - Nutritive (e.g., sucrose) and non-nutritive (e.g., saccharin) sweeteners
      stimulate intake in inbred mouse strains. BALB/c, SWR and C57BL/6 mice differ in
      the ability of dopamine (DA) D1 (SCH23390) and opioid (naltrexone) receptor
      antagonism to alter sucrose intake. Whereas SCH23390 comparably reduced
      cumulative sucrose intake in all three strains, naltrexone reduced cumulative
      sucrose intake maximally in C57/BL/6 mice, in intermediate fashion in BALB/c
      mice, but not in SWR mice. Whereas cumulative saccharin intake was reduced by DA
      D1 receptor antagonism in BALB/c and SWR mice, naltrexone was more potent in SWR
      relative to BALB/c mice. The present study first examined whether SCH23390 (50
      1600nmol/kg) and naltrexone (0.01-5mg/kg) altered saccharin intake in C57BL/6
      mice. Given that scopolamine (SCOP), a muscarinic cholinergic receptor
      antagonist, reduces sweet intake in outbred rats, a second experiment examined
      whether SCOP (0.1-10mg/kg) altered 0.2% saccharin and 10% sucrose intakes in
      BALB/c, SWR and C57BL/6 mice. Cumulative saccharin intake was significantly
      reduced by SCH23390 (200-1600nmol/kg; ID40=175nmol/kg) and naltrexone (0.1
      5mg/kg; ID40>5mg/kg) in C57BL/6 mice. Cumulative sucrose intake was significantly
      reduced following SCOP in C57BL/6 (0.1-10mg/kg; ID40=2.32mg/kg) and BALB/c (2.5
      10mg/kg; ID40=0.52mg/kg) mice. In contrast, SWR mice (ID40=41.61mg/kg) only
      displayed transient (15min) reductions in sucrose intake following SCOP (2.5
      10mg/kg). Cumulative saccharin intake was significantly reduced following SCOP in
      C57BL/6 and BALB/c mice (0.1-10mg/kg; ID40<0.1mg/kg). In contrast, SWR mice
      (ID40=2.28mg/kg) displayed smaller significant reductions in saccharin intake
      following SCOP (0.1-10mg/kg). These data indicate that although both nutritive
      and non-nutritive sweet intakes are governed by muscarinic cholinergic receptor
      signaling, this process is subject to murine genetic variance with greater
      sensitivity observed in C57BL/6 and BALB/c relative to SWR inbred mouse strains.

PMID- 29042248
TI  - The antidepressant- and anxiolytic-like effects of fluoxetine and clozapine in
      chronically isolated rats involve inhibition of hippocampal TNF-alpha.
AB  - Brain oxidative stress and neuroinflammation are implicated in psychiatric
      disorders. Thus, it is important to investigate the effects of individual
      psychotropic agents on antioxidative defense and proinflammatory mediators in
      brain regions associated with these disorders. Psychosocial stress is recognized
      as a threat to mental health, and the hippocampus is a primary target of stress
      related damage. Chronic social isolation (CSIS) is a mild psychosocial stress
      used to model the pathophysiology of depression. We examined the antioxidative
      and anti-inflammatory potential of the antidepressant fluoxetine (FLX) and
      atypical antipsychotic clozapine (CLZ) in the hippocampus in the CSIS model of
      depression. We measured the effects of FLX and CLZ on depressive- and anxiety
      like behaviors in non-stressed rats and rats exposed to 21d of CSIS. We further
      evaluated the content of reduced glutathione (GSH), the protein expression and
      activity of the GSH-related enzymes, the subcellular localization of nuclear
      factor-kappa B (NF-kappaB) and protein levels of proinflammatory mediators
      cyclooxygenase-2 (COX-2), interleukin-1beta (IL-1beta), and tumor necrosis factor
      alpha (TNF-alpha) in these groups of rats. CSIS resulted in an increase in
      depressive- and anxiety-like behaviors that corresponded with compromised
      glutathione peroxidase (GPx)-mediated antioxidative defense and increased TNF
      alpha, but not with changes in NF-kappaB, IL-1beta and COX-2 levels. FLX and CLZ,
      applied during CSIS, prevented the behavioral changes associated with CSIS, and
      inhibited the increase in TNF-alpha, but did not affect GPx-mediated
      antioxidative defense. Furthermore, both drugs decreased hippocampal GPx activity
      when applied to non-stressed rats. These results emphasize the significance of
      hippocampal TNF-alpha-mediated proinflammmatory signaling in the pathophysiology
      of depressive symptoms and the importance of the anti-inflammatory action of both
      FLX and CLZ in the prevention of these symptoms.

PMID- 29042249
TI  - Prevalence and biochemical risk factors of diabetic peripheral neuropathy with or
      without neuropathic pain in Taiwanese adults with type 2 diabetes mellitus.
AB  - AIMS: To investigate the prevalence and risk factors for diabetic peripheral
      neuropathy with or without neuropathic pain in Taiwanese. METHODS: A cross
      sectional, hospital-based observational study was conducted. We enrolled 2837
      adults with type 2 diabetes mellitus. Diabetic peripheral neuropathy with or
      without pain were diagnosed using 2 validated screening tools, namely the
      Michigan Neuropathy Screening Instrument and Douleur Neuropathique 4
      questionnaire. RESULTS: In our sample, 2233 participants had no neuropathy, 476
      had diabetic peripheral neuropathy without pain, and 128 had diabetic peripheral
      neuropathy with neuropathic pain, representing an overall diabetic peripheral
      neuropathy prevalence of 21.3%, and the prevalence of neuropathic pain in
      diabetic peripheral neuropathy was 21.2%. Multivariate analysis revealed that
      older age (P<0.001), treatment with insulin (P=0.004), microalbuminuria (P=0.001)
      or overt proteinuria (P<0.001) were independently associated with diabetic
      peripheral neuropathy, whereas older age (P<0.001), elevated glycated haemoglobin
      (P=0.011), lower high-density lipoprotein cholesterol (P=0.033), and overt
      proteinuria (P<0.001) were independently associated with diabetic peripheral
      neuropathy with neuropathic pain. CONCLUSIONS: During clinical visits involving
      biochemical studies, the risk for diabetic peripheral neuropathy with neuropathic
      pain should be considered for people with older age, elevated glycated
      haemoglobin, low high-density lipoprotein cholesterol and overt proteinuria, with
      particular attention given to increased levels of albuminuria while concerning
      neuropathic pain.

PMID- 29042250
TI  - Eating breakfast and snacks while television viewing are associated with some
      cardio metabolic risk factors among Iranian children.
AB  - AIM: We aimed to investigate the association of eating meals while television
      viewing (TVV) and screen-based behaviors with cardio metabolic risk factors
      (CRFs) among school-aged children in Shiraz. MATERIALS AND METHODS: This cross
      sectional study was done on 409 primary school children (217 boys), aged 6-9
      years. Physical activity, time spent on screen-based behaviors and frequency of
      eating meals while TVV were measured using a questionnaire. Anthropometric
      indices, fasting blood sugar (FBS), blood lipids, blood pressure (BP), dietary
      intakes and physical activity were assessed. Association of eating while TVV with
      CRFs were assessed using linear regression, adjusted for potential confounders.
      All statistical analysis were conducted using the Stata 13 software. RESULTS:
      Fully adjusted model showed that TVV time had significant positive association
      with waist circumferences (WC), and BP (p <0.05). Also, we found an inverse
      relationship between using Computer and Video games with TG level (beta=-0.3; CI:
      -0.64, -0.09). Children who ate two or more breakfast meal while TVV had higher
      WC (beta=2.02; CI: 0.51, 3.53) and FBS (beta=3.58; CI: 0.39, 6.78) compared to
      who never ate breakfast while TVV. After adjustment for Screen time and BMI,
      eating snacks while TVV was positively associated with FBS and systolic BP.
      However, Eating dinner and lunch while TVV were not significantly associated with
      any of CRFs after adjustment for confounders. CONCLUSIONS: We found that both
      eating breakfast and snacks while TVV were associated with WC, FBS and BP in
      children. Also, excessive TVV was associated with WC and BP.

PMID- 29042251
TI  - Effects of heparan sulfate proteoglycan syndecan-4 on the insulin secretory
      response in a mouse pancreatic beta-cell line, MIN6.
AB  - Heparan sulfate proteoglycans (HSPGs) comprise a core protein to which
      extracellular glycosaminoglycan chains are attached. Syndecan-4, one of the major
      HS-containing core proteins, is distributed on the cell surface, where they
      interact with various protein ligands and regulate a wide range of biological
      activities. Here, we propose that the core protein of HSPGs is involved in the
      insulin secretory response. To investigate the participation of HSPGs in the
      insulin-secretion mechanism, MIN6 cells, a mouse pancreatic beta-cell line, were
      subcloned. The subcloned MIN6 cells were selected based on their insulin
      secretory response, the expression of HS and core proteins. The results from
      these screening experiments indicated that only syndecan-4-expressing subclones
      are able to secrete insulin in response to glucose. Silencing of syndecan-4
      reduced glucose-induced insulin secretion, whereas the overexpression of syndecan
      4 increased the insulin secretory response. These data indicate that the HSPG
      syndecan-4 plays important role(s) in the insulin secretory response.

PMID- 29042252
TI  - The roles and applications of autoantibodies in progression, diagnosis, treatment
      and prognosis of human malignant tumours.
AB  - The existence of autoantibodies towards an individual's own proteins or nucleic
      acids has been established for more than 100years, and for a long period, these
      autoantibodies have been believed to be closely associated with autoimmune
      diseases. However, in recent years, researchers have become more interested in
      the role and application of autoantibodies in progression, diagnosis, treatment
      and prognosis of human malignant tumours. Over the past few decades, numerous
      epidemiological studies have shown that the risk of certain cancers is
      significantly altered (increased or decreased) in patients with autoimmune
      diseases, which suggests that autoantibodies may play either promoting or
      suppressing roles in cancer progression. The idea that autoantibodies are
      directly involved in tumour progression gains special support by the findings
      that some antibodies secreted by a variety of cancer cells can promote their
      proliferation and metastasis. Because the cancer cells generate cell antigenic
      changes (neoantigens), which trigger the immune system to produce autoantibodies,
      serum autoantibodies against tumour-associated antigens have been established as
      a novel type of cancer biomarkers and have been extensively studied in different
      types of cancer. The autoantibodies as biomarkers in cancer diagnosis are not
      only more sensitive and specific than antigens, but also could appear before
      clinical evidences of the tumours, thus disclosing them. The observations that
      cancer risk is lower in patients with some autoimmune diseases suggest that
      certain autoantibodies may be protective from certain cancers. Moreover, the
      presence of autoantibodies in healthy individuals implies that it could be safe
      to employ autoantibodies to treat cancer. Of note, an autoantibodies derived from
      lupus murine model received much attention due to their selective cytotoxicity
      for malignant tumour cell without harming normal ones. These studies showed the
      therapeutic value of autoantibodies in cancer. In this review, we revisited the
      pathological or protective role of autoantibodies in cancer progression,
      summarize the application of autoantibodies in cancer diagnosis and prognosis,
      and discuss the value of autoantibodies in cancer therapy. The studies
      established to date suggest that autoantibodies not only regulate cancer
      progression but also promise to be valuable instruments in oncological diagnosis
      and therapy.

PMID- 29042253
TI  - Calcium uptake and cytochrome c release from normal and ischemic brain
      mitochondria.
AB  - At abnormally elevated levels of intracellular Ca2+, mitochondrial Ca2+ uptake
      may compromise mitochondrial electron transport activities and trigger membrane
      permeability changes that allow for release of cytochrome c and other
      mitochondrial apoptotic proteins into the cytosol. In this study, a clinically
      relevant canine cardiac arrest model was used to assess the effects of global
      cerebral ischemia and reperfusion on mitochondrial Ca2+ uptake capacity, Ca2+
      uptake-mediated inhibition of respiration, and Ca2+-induced cytochrome c release,
      as measured in vitro in a K+-based medium in the presence of Mg2+, ATP, and NADH
      linked oxidizable substrates. Maximum Ca2+ uptake by frontal cortex mitochondria
      was significantly lower following 10 min cardiac arrest compared to non-ischemic
      controls. Mitochondria from ischemic brains were also more sensitive to the
      respiratory inhibition associated with accumulation of large levels of Ca2+.
      Cytochrome c was released from brain mitochondria in vitro in a Ca2+-dose
      dependent manner and was more pronounced following both 10 min of ischemia alone
      and following 24 h reperfusion, in comparison to mitochondria from non-ischemic
      Shams. These effects of ischemia and reperfusion on brain mitochondria could
      compromise intracellular Ca2+ homeostasis, decrease aerobic and increase
      anaerobic cerebral energy metabolism, and potentiate the cytochrome c-dependent
      induction of apoptosis, when re-oxygenated mitochondria are exposed to abnormally
      high levels of intracellular Ca2+.

PMID- 29042254
TI  - Cardiac sodium channel antagonism - Translation of preclinical in vitro assays to
      clinical QRS prolongation.
AB  - INTRODUCTION: Cardiac sodium channel antagonists have historically been used to
      treat cardiac arrhythmias by preventing the reentry of the electrical impulse
      that could occur following myocardial damage. However, clinical studies have
      highlighted a significant increase in mortality associated with such treatment.
      Cardiac sodium channel antagonist activity is now seen as an off-target
      pharmacology that should be mitigated during the drug development process. The
      aim of this study was to examine the correlation between in vitro/ex vivo assays
      that are routinely used to measure Nav1.5 activity and determine the
      translatability of the individual assays to QRS prolongation in the clinic.
      METHODS: A set of clinical compounds with known Nav1.5 activity was profiled in
      several in vitro/ex vivo assays (binding, membrane potential, patch clamp and the
      Langendorff isolated heart). Clinical data comprising compound exposure levels
      and changes in QRS interval were obtained from the literature.
      Sensitivity/specificity analysis was performed with respect to the clinical
      outcome. RESULTS: The in vitro assays showed utility in predicting QRS
      prolongation in the clinic. Optimal thresholds were defined for each assay
      (binding: IC20; membrane potential: IC10; patch clamp: IC20) and sensitivity (69
      88%) and specificity (53-84%) values were shown to be similar between assay
      formats. DISCUSSION: The data provide clear statistical insight into the
      translatability of Nav1.5 antagonism data generated in vitro to potential
      clinical outcomes. These results improve our ability to understand the liability
      posed by such activity in novel development compounds at an early stage.

PMID- 29042255
TI  - Comparison of RAW264.7, human whole blood and PBMC assays to screen for
      immunomodulators.
AB  - The RAW264.7 mouse macrophage cell line is used extensively to carry out in vitro
      screens for immunomodulators. Compounds that are effective at reducing the
      expression of pro-inflammatory cytokines or nitric oxide (NO) from
      lipopolysaccharide (LPS)-stimulated RAW264.7 cells are often considered candidate
      anti-inflammatory agents for humans. There is, however, very little data on the
      reliability of this screen to identify bona fide human immunomodulators. We
      compared the efficacy of 37 purported immunomodulators to modulate LPS or E. coli
      induced inflammatory responses in RAW264.7 cell, whole human blood and human
      peripheral blood mononuclear cell (PBMC) assays. Interestingly, there was no
      significant correlation (R=0.315) between the responses obtained with RAW264.7
      cells and the whole blood assay (WBA), suggesting that compounds demonstrating
      efficacy in RAW264.7 cells may be ineffective in humans, and, more importantly,
      compounds that are effective in humans may be missed with a RAW264.7 screen.
      Interestingly, there was also no significant correlation between the WBA and
      human PBMCs when the latter were cultured with 10% FCS, but a moderate
      correlation was seen when the PBMCs were cultured with 25% autologous plasma. The
      presence of plasma thus contributes to the overall inflammatory response observed
      in the WBA. We then asked if RAW264.7 cells, given that they are mouse macrophage
      like cells, respond in a manner similar to primary murine derived macrophages.
      Intriguingly, there was no significant correlation (R=0.012) with the 37 putative
      immunomodulators, pointing to distinct inflammatory response mechanisms in the
      two model systems. We conclude that the use of a WBA to confirm potential
      immunomodulators obtained from high throughput screening with RAW264.7 cells is
      advisable and that future screens be carried out using a WBA.

PMID- 29042256
TI  - Antiseptic effects of dabrafenib on TGFBIp-induced septic responses.
AB  - Transforming growth factor-beta-induced protein (TGFBIp), an extracellular
      protein, is expressed on several cell types in response to TGF-beta stimulation.
      Human umbilical vein endothelial cell (HUVEC)-derived TGFBIp functions as a
      mediator of sepsis. Screening of bioactive compound libraries is an effective
      approach for repositioning FDA-approved drugs or discovering new treatments for
      human diseases (drug repositioning). Dabrafenib (DAB), a B-Raf inhibitor, was
      initially used for treating metastatic melanoma. The present study determined
      whether DAB modulated TGFBIp-mediated septic responses in HUVECs and in mice.
      Antiseptic functions of DAB were examined by measuring permeability, leukocyte
      adhesion and migration, and proinflammatory protein activation in TGFBIp
      stimulated HUVECs and mice. In addition, beneficial effects of DAB on survival
      rate were examined using a mouse model of sepsis. We found that DAB inhibited
      TGFBIp-induced vascular barrier disruption, cell adhesion molecule (CAM)
      expression, and neutrophil adhesion/transendothelial migration toward human
      endothelial cells. DAB also suppressed TGFBIp-induced hyperpermeability and
      leukocyte migration in vivo. These results suggest that DAB exerts anti
      inflammatory effects by inhibiting hyperpermeability, CAM expression, and
      leukocyte adhesion and migration, indicating its utility for treating vascular
      inflammatory diseases.

PMID- 29042257
TI  - In vivo pharmacokinetic interaction by ethanolic extract of Gymnema sylvestre
      with CYP2C9 (Tolbutamide), CYP3A4 (Amlodipine) and CYP1A2 (Phenacetin) in rats.
AB  - Gymnema sylvestre (GS) is a medicinal herb used for diabetes mellitus (DM). Herbs
      are gaining popularity as medicines in DM for its safety purpose. The aim of the
      present study was to evaluate in vivo pharmacokinetic (PK) interaction between
      allopathic drugs tolbutamide (TOLBU), amlodipine (AMLO), and phenacetin (PHENA)
      at low (L) and high (H) doses with ethanolic extract (EL) from GS. EL was
      extracted and subjected to TLC, total triterpenoid content (19.76 +/- 0.02 W/W)
      and sterol content (0.1837 +/- 0.0046 W/W) estimation followed by identification
      of phytoconstituents using HRLC-MS and GC-MS. PK interaction study with CYP2C9,
      CYP3A4 and CYP1A2 enzymes were assessed using TOLBU, AMLO and PHENA respectively
      to index cytochrome (CYP) mediated interaction in rats after concomitant
      administration of EL extract (400 mg/kg) from GS for 7 days. The rats were
      divided into four groups for each PK study where, group I and II were positive
      control for low and high dose of test drugs (CYP substrates) while group II and
      IV were orally administered EL. The PK study result of PHENA indicated that area
      under the plasma concentration-time curve (AUC0-24) was significantly (P <
      0.0001) increased by 1.4 (L) and 1.3-fold (H), plasma concentration (Cmax) was
      significantly (P < 0.001) increased by 1.6 (L) and 1.4-fold (H). Whereas for
      TOLBU; clearance rate (CL) was significantly (P < 0.0001) decreased by 2.4 (L)
      and 2.3-fold (H), Cmax, was significantly (P < 0.001) decreased by 26.5% (L) and
      50.4% (H) and AUC0-24 was significantly (P < 0.0001) decreased by 59.8% (L) and
      57.5% (H). Thus, EL is seen to be interacting with CYP1A2 by inhibiting its
      metabolic activity. HRLC-MS and GC-MS helped identify the presence of gymnemic
      acid (GA), triterpenoids and steroids in EL which could be the reason for PK
      interaction of CYP1A2 and CYP2C9. Also, in silico structure based site of
      metabolism study showed Fe accessibility and intrinsic activity for GA-IV, GA-VI,
      GA-VII and GA-X with CYP2C9. PK parameters of AMLO were not significantly
      affected by pre-treatment of EL. Thereby our findings indicate that co
      administration of GS with drugs that are metabolized by CYP2C9 and CYP1A2 could
      lead to potential HDI.

PMID- 29042258
TI  - An open-source method to analyze optokinetic reflex responses in larval
      zebrafish.
AB  - BACKGROUND: Optokinetic reflex (OKR) responses provide a convenient means to
      evaluate oculomotor, integrative and afferent visual function in larval zebrafish
      models, which are commonly used to elucidate molecular mechanisms underlying
      development, disease and repair of the vertebrate nervous system. NEW METHOD: We
      developed an open-source MATLAB-based solution for automated quantitative
      analysis of OKR responses in larval zebrafish. The package includes applications
      to: (i) generate sinusoidally-transformed animated grating patterns suitable for
      projection onto a cylindrical screen to elicit the OKR; (ii) determine and record
      the angular orientations of the eyes in each frame of a video recording showing
      the OKR response; and (iii) analyze angular orientation data from the tracking
      program to yield a set of parameters that quantify essential elements of the OKR.
      The method can be employed without modification using the operating manual
      provided. In addition, annotated source code is included, allowing users to
      modify or adapt the software for other applications. RESULTS: We validated the
      algorithms and measured OKR responses in normal larval zebrafish, showing good
      agreement with published quantitative data, where available. COMPARISON WITH
      EXISTING METHOD(S): We provide the first open-source method to elicit and analyze
      the OKR in larval zebrafish. The wide range of parameters that are automatically
      quantified by our algorithms significantly expands the scope of quantitative
      analysis previously reported. CONCLUSIONS: Our method for quantifying OKR
      responses will be useful for numerous applications in neuroscience using the
      genetically- and chemically-tractable zebrafish model.

PMID- 29042259
TI  - Widespread optogenetic expression in macaque cortex obtained with MR-guided,
      convection enhanced delivery (CED) of AAV vector to the thalamus.
AB  - BACKGROUND: In non-human primate (NHP) optogenetics, infecting large cortical
      areas with viral vectors is often a difficult and time-consuming task. Previous
      work has shown that parenchymal delivery of adeno-associated virus (AAV) in the
      thalamus by convection-enhanced delivery (CED) can lead to large-scale
      transduction via axonal transport in distal areas including cortex. We used this
      approach to obtain widespread cortical expression of light-sensitive ion
      channels. NEW METHOD: AAV vectors co-expressing channelrhodopsin-2 (ChR2) and
      yellow fluorescent protein (YFP) genes were infused into thalamus of three rhesus
      macaques under MR-guided CED. After six to twelve weeks recovery, in vivo optical
      stimulation and single cell recording in the cortex was carried out using an
      optrode in anesthetized animals. Post-mortem immunostaining against YFP was used
      to estimate the distribution and level of expression of ChR2 in thalamus and
      cortex. RESULTS: Histological analysis revealed high levels of transduction in
      cortical layers. The patterns of expression were consistent with known thalamo
      cortico-thalamic circuits. Dense expression was seen in thalamocortiocal axonal
      fibers in layers III, IV and VI and in pyramidal neurons in layers V and VI,
      presumably corticothalamic neurons. In addition we obtained reliable in vivo
      light-evoked responses in cortical areas with high levels of expression.
      COMPARISON WITH EXISTING METHODS: Thalamic CED is very efficient in achieving
      large expressing areas in comparison to convectional techniques both in
      minimizing infusion time and in minimizing damage to the brain. CONCLUSION: MR
      guided CED infusion into thalamus provides a simplified approach to transduce
      large cortical areas by thalamo-cortico-thalamic projections in primate brain.

PMID- 29042260
TI  - PLDT (planarian light/dark test): an invertebrate assay to quantify defensive
      responding and study anxiety-like effects.
AB  - BACKGROUND: Planarians, like rodents, instinctively spend more time in dark
      versus light environments when given a choice. This behavioral phenomenon is
      called negative phototaxis, which may reflect defensive responding related to an
      anxiety-like phenotype. NEW METHOD: We propose a planarian light/dark test,
      designated PLDT, to predict anxiogenic- or anxiolytic-like effects.
      Experimentally, we placed a planarian at the midline of a Petri dish, containing
      test compound or water, that was split evenly into light and dark compartments
      and determined time spent in the light over 10min. RESULTS: A clinically-approved
      benzodiazepine agonist (clorazepate; 10MUM) increased time spent in the light
      whereas an inverse benzodiazepine agonist (FG-7142; 1, 10MUM) produced the
      opposite response. Fluoxetine (1MUM) or ethanol (1%), as well as the 'bath salt'
      cathinone S-mephedrone (300MUM), enhanced time spent in the light. Planarians
      exposed to predator (frog) odor spent more time in the dark. COMPARISON WITH
      EXISTING METHODS: The light/dark box (LDB) test in rodents is used to screen
      putative medications for possible anxiolytic and anxiogenic effects. Our results
      showing that time spent in the light by planarians is enhanced by common anxiety
      relieving drugs (e.g. benzodiazepine agonist, ethanol, fluoxetine) and decreased
      by anxiogenic substances (e.g. predator odor, benzodiazepine inverse agonist)
      reveal directionally similar effects in the established (LDB) and new (PLDT)
      assays. CONCLUSION: Our data identify the PLDT as a cost-effective, invertebrate
      assay for quantifying the effects of practically any water-soluble substance on
      defensive responding and for studying and teaching anxiety-like responses in a
      living organism.

PMID- 29042261
TI  - Biology of the introduced species Triatoma lecticularia (Hemiptera: Reduviidae)
      to northwestern Mexico, under laboratory conditions.
AB  - The first record of Triatoma lecticularia out of its reported distribution area
      together with the brief description of the said area is provided in this paper.
      In addition, some biological parameters related to hatching of eggs, life cycle
      and feeding and defecation behaviors for each instar of one population of T.
      lecticularia from its previously reported distribution area (PR) and for each
      instar of that introduced recently found population (IS) of this species were
      evaluated and compared. Twenty-eight specimens were collected from IS, mostly
      (64.29%) from peridomestic areas (mainly chicken coops). No significant (p>0.05)
      differences were recorded between the two studied cohorts in their average time
      to hatch, which was close to 19days. The median egg-to-adult development time,
      the number of blood meals at each nymphal, the instar mortality rates and median
      time-lapse for beginning of feeding were significantly (p<0.05) shorter for the
      IS cohort. Median feeding time was higher in PR. Defecation delay was shorter
      than 10min in both studied cohorts. Given these results, the introduced recently
      found population of T. lecticularia could be considered an important potential
      vector of Trypanosoma cruzi to human populations and could replace main
      triatomine species on its new distribution area.

PMID- 29042262
TI  - Molecular epidemiology and in vitro evidence suggest that Leishmania braziliensis
      strain helps determine antimony response among American tegumenary leishmaniasis
      patients.
AB  - Antimony is the first line drug for treating American tegumentary leishmaniasis
      (ATL) in Brazil. In this country, Leishmania braziliensis causes at least three
      distinct forms of disease: localized cutaneous (CL), mucosal (ML) and
      disseminated leishmaniasis (DL). All forms can be found in Corte de Pedra,
      Northeast Brazil. ML and DL respond poorly to antimony, in contrast to CL. The L.
      braziliensis population causing ATL in Corte de Pedra is genetically very
      diverse, with strains of the parasite associating with the clinical form of
      leishmaniasis. We tested the hypotheses that antimony refractoriness is
      associated with L. braziliensis genotypes, and that parasites from ML and DL
      present greater in vitro resistance to antimony than L. braziliensis from CL.
      Comparison of geographic coordinates of living sites between antimony responders
      and non-responders by Cusick and Edwards test showed that refractoriness and
      responsiveness to the drug were similarly wide spread in the region (p>0.05).
      Parasites were then genotyped by sequencing a locus starting at position 425,451
      on chromosome 28, which is polymorphic among L. braziliensis of Corte de Pedra.
      Haplotype CC- in CHR28/425,451 was associated with risk of treatment failure
      among CL patients (Fishers exact test, p=0.03, odds ratio=4.65). This haplotype
      could not be found among parasites from ML or DL. Finally, sensitivity to
      antimony was evaluated exposing L. braziliensis promastigotes to increasing
      concentrations of meglumine antimoniate in vitro. Parasites from ML and DL were
      more resistant to antimony at doses of 2mg/100MUL and beyond than those isolated
      from CL (Fisher's exact test, p=0.02 and p=0.004, respectively). The
      intrinsically lower susceptibility of L. brazliensis from ML and DL to antimony
      parallels what is observed for patients' responsiveness in the field. This
      finding reinforces that ML and DL patients would benefit from initiating
      treatment with drugs currently considered as second line, like amphotericin B.

PMID- 29042263
TI  - Facility-Level Factors and Outcomes After Skilled Nursing Facility Admission for
      Trauma and Surgical Patients.
AB  - OBJECTIVE: Patients discharged to skilled nursing facilities (SNFs) have worse
      outcomes than those discharged to home, but whether this is due to differences in
      facility-level factors in addition to patient characteristics is not known. We
      aimed to determine whether SNF-level factors including nurse staffing and patient
      density are associated with outcomes after acute hospitalization for trauma or
      surgery. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Retrospective study of
      patients discharged to Medicare-certified SNFs after trauma or major surgery from
      2007 to 2009. We measured the ratio of beds per nurse and the proportion of
      trauma and surgery patients at each facility (density). Outcomes were 1-year
      mortality, hospital readmission, and failure to discharge home at first discharge
      disposition. RESULTS: For 389,133 patients (mean age 78 years, 63% female)
      admitted to 3707 SNFs, mortality was 26%, hospital readmission 26%, and failure
      to discharge home 44%. After adjusting for patient-level factors, SNFs with fewer
      beds per nurse had lower odds of mortality [odds ratio (OR): trauma 0.84; (95%
      confidence interval: 0.77-0.91), surgery 0.80 (0.75-0.86)], readmission [OR:
      trauma 0.81 (0.74-0.88), surgery 0.71 (0.65-0.76)], and failure to discharge home
      [OR: trauma 0.82 [0.74-0.91], surgery 0.66 [0.60-0.72]). SNFs with greater
      density of specialty patients (>4.3% surgery, >14.1% trauma) had lower odds of
      readmission [OR: trauma 0.59 (0.53-0.66), surgery 0.62 (0.58-0.67)] and failure
      to discharge home [OR: trauma 0.48 (0.43-0.55), surgery 0.45 (0.42-0.49)].
      CONCLUSIONS: There are modifiable SNF-level factors that influence long-term
      outcomes and may be targets for intervention. Staffing standardization and SNF
      specialization may reduce variation of quality in post-acute care.

PMID- 29042264
TI  - Association Between Sodium Excretion and Cardiovascular Disease and Mortality in
      the Elderly: A Cohort Study.
AB  - OBJECTIVE: High dietary sodium intake is a risk factor for cardiovascular events
      and death. Recently, a J-shaped correlation between sodium intake and adverse
      outcomes has been shown. The evidence on the association between sodium intake
      and cardiovascular outcomes in the elderly is scant. The objective of this study
      was to evaluate the correlation between sodium intake and cardiovascular events
      and mortality in an elderly population, taking into account frailty status.
      DESIGN: Cohort study of community dwelling older people enrolled in the InCHIANTI
      (Invecchiare in Chianti - Aging in the Chianti) study from 1998 to 2000 and
      followed-up for 9 years. SETTING: Two communities in Tuscany, Italy.
      PARTICIPANTS: A total of 920 participants 65 years of age and older, with 24-hour
      urinary sodium excretion data. MEASUREMENTS: Nine-year mortality and incident
      cardiovascular events were analyzed using Cox and nonlinear log-binomial models,
      stratified by frailty status. Sensitivity analysis in participants without
      hypertension and cardiovascular diseases was performed. RESULTS: Mean age of the
      population was 74.5 years (standard deviation 6.99); 55.4% were women. There was
      a bi-modal association between sodium excretion and mortality, with risk
      increasing only below sodium excretion of 6.25 g/d [hazard ratio (HR) 1.29, 95%
      confidence interval (CI) 1.20-1.38], confirmed in the adjusted model (HR 1.12,
      95% CI 1.04-1.22). These results were confirmed in participants without
      cardiovascular diseases. After stratification for frailty phenotype, the
      association was stronger in frail participants (adjusted HR 1.23, 95% CI 1.02
      1.50 vs HR 1.11, 95% CI 1.01-1.22 in robust participants). There was no
      association between 24-hour sodium excretion and 9-year incidence of
      cardiovascular diseases (adjusted risk ratio 0.96, 95% CI 0.90-1.02).
      CONCLUSIONS: Reduced sodium excretion is associated with increased mortality in a
      sample of community-dwelling older people, especially among the frail
      participants. High levels of sodium excretion are not associated with adverse
      outcomes in this population; therefore, sodium restriction might not be
      beneficial in older people.

PMID- 29042265
TI  - Preliminary Evidence of a Positive Effect of Occupational Therapy in Patients
      With Delirium Superimposed on Dementia.

PMID- 29042266
TI  - Development and Validation of the Symptom Assessment to Improve Symptom Control
      for Institutionalized Elderly Scale.
AB  - OBJECTIVES: To validate a newly developed multiple symptom self-assessment tool
      in nursing homes. DESIGN: Thirty prevalent symptoms identified in the literature
      were classified by a 2-round Delphi procedure to a top 10 of the most relevant,
      burdensome symptoms. Because no existing symptom scale fully covered this top 10,
      we developed a new scale, consisting of a horizontal numerical scale for the top
      10 symptoms, with the possibility to add and rate 3 other symptoms. This scale
      was validated. SETTING AND PARTICIPANTS: Hundred seventy-four participants, mean
      age 85 (+/-5.94) years, were recruited from 7 nursing homes (86%) and 3 acute
      geriatric wards (14%). METHODS: To test the construct validity, participants with
      and without a palliative status were enrolled. Participants completed the Symptom
      Assessment to Improve Symptom Control for Institutionalized Elderly (SATISFIE)
      scale on day 0 and day 1 (intrarater reliability). Nurses completed the scale on
      day 0 (inter-rater reliability). Descriptive statistics described the
      characteristics of the study population and symptom scores. Differences in
      symptom scores between palliative and nonpalliative participants were analyzed
      with the Mann-Whitney U test. Intrarater and inter-rater reliability were
      calculated by means of an intraclass correlation coefficient. Factor analysis
      searched for possible symptom clusters. Feasibility was evaluated by measuring
      the assessment time and by providing a questionnaire for the nurses. RESULTS: In
      the nonpalliative group (n = 130), the highest self-rated median scores were pain
      on day 1 [median 3, interquartile range (IQR) 0-5] and pain on day 2. In the
      palliative group (n = 44), the highest median self-rated scores were fatigue on
      day 1 [median 5 (IQR 0-6)], lack of energy on day 1 and 2 [both median 5 (IQR 0
      8)]; and depressed feeling on day 2 [median 3 (IQR 0-5)]. Nurse assessments
      median scores were the highest for depressed feeling [median 5 (IQR 1-7)],
      fatigue [median 4.5 (IQR 0-6.5)], and lack of energy, [median 3 (IQR 0-6)] in the
      palliative group. In the nonpalliative group, none of the median scores was 3 or
      more. Intraclass correlation coefficients for intrarater reliability varied
      between 0.65 and 0.89 and for inter-rater reliability (patients-nurses) between
      0.18 and 0.63. Mean assessment time for nurses was 2.0 minutes [standard
      deviation (SD) = 1.01]. For participants, it decreased from 10.5 minutes (SD =
      5.41) at the first assessment to 7.5 minutes (SD = 3.72) at the second
      assessment. Nurses determined the SATISFIE instrument to be useful, applicable in
      daily practice, and sufficiently comprehensible for the patients. CONCLUSIONS:
      The SATISFIE scale is a valid and feasible instrument for regular, multiple
      symptom assessment in institutionalized older persons.

PMID- 29042267
TI  - Initiating pain in osteoarthritis (OA): is it the mast cell?

PMID- 29042268
TI  - Rice Information GateWay: A Comprehensive Bioinformatics Platform for Indica Rice
      Genomes.

PMID- 29042269
TI  - The comparison of acute high-intensity interval exercise vs. continuous moderate
      intensity exercise on plasma calprotectin and associated inflammatory mediators.
AB  - PURPOSE: Calprotectin promotes the release of inflammatory mediators (e.g.,
      monocyte chemoattractant protein-1 [MCP-1] and myeloperoxidase [MPO]) during the
      innate immune response as a mechanism to augment leukocyte chemotaxis and
      phagocytosis. Although plasma calprotectin is elevated with traditional
      continuous moderate-intensity exercise (CME) as an indicator of the inflammatory
      response, high-intensity interval exercise (HIIE) has been shown to attenuate
      systemic inflammation while providing similar improvements in cardiovascular
      health. Therefore, the purpose of this study was to compare plasma levels of
      calprotectin, MCP-1, and MPO between acute HIIE vs. CME. METHODS: Nine healthy
      males (24.67+/-3.27yrs) were recruited to participate in HIIE and CME on a cycle
      ergometer. HIIE consisted of 10 repeated 60s of cycling at 90% max watts (Wmax)
      separated by 2min of active recovery intensity of interval exercise, whereas CME
      consisted of 28min of cycling at 60% Wmax. Blood samples were collected prior to,
      immediately post, and 30 and 60min into recovery following exercise. RESULTS:
      Acute HIIE elicited a lower elevation in calprotectin and MPO compared to CME. An
      increase in MCP-1 was observed across time in both exercise protocols.
      Furthermore, our analyses did not reveal any significant correlation in percent
      change (baseline to immediately following exercise) among calprotectin, MCP1, and
      MPO in neither HIIE nor CME. However, a significant positive correlation was
      observed in the overall release of calprotectin and MPO across all four time
      points in both HIIE and CME. Conclusions Our findings indicate that acute HIIE
      may potentially diminish the systemic release of inflammatory mediators
      (calprotectin and MPO) compared to CME.

PMID- 29042270
TI  - Regression of Paraneoplastic Rash after Lung Cancer Chemotherapy.

PMID- 29042271
TI  - Blockade of the orexin receptors in the CA1 region of hippocampus decreased the
      lateral hypothalamic-induced antinociceptive responses in the model of orofacial
      formalin test in the rats.
AB  - The role of hippocampus and lateral hypothalamus (LH) in modulation of formalin
      induced nociception has been established. The present study aims to examine the
      role of orexin receptors in the Cornu Ammonis 1 (CA1) region of hippocampus in
      modulation of the LH-induced antinociception in the orofacial formalin test. Male
      Wistar rats were unilaterally implanted with two cannulae into the LH and CA1.
      Intra-LH microinjection of carbachol was done 5min after intra-CA1 administration
      of SB-334867 (OX1R antagonist) or TCS OX2 29 (OX2R antagonist). After 5min, 50MUl
      of 1% formalin was subcutaneously injected into the upper lip for inducing the
      nociceptive behaviors. Solely intra-LH administration of carbachol reduced early
      and late phases of formalin-induced orofacial nociception in a dose-dependent
      manner. The antinociception evoked by intra-LH injection of carbachol (0.5MUl of
      250nM carbachol) was antagonized by intra-CA1 administration of 0.5MUl of 3, 10
      and 30nM solutions of SB-334867 or TCS OX2 29 during the early and late phases of
      orofacial formalin test. This effect was more remarkable during the late phase in
      comparison to the early phase. In addition, anti-analgesic effect of SB-334867
      was more than TCS OX2 29 during the early and late phases. The results suggest
      the interpretation that a neural pathway from the LH to the CA1 probably
      contributes to the modulation of formalin-induced orofacial nociception through
      recruitment of both CA1 orexin receptors. Clinical studies are recommended to
      study the probable effectiveness of orexinergic system in modulation of the
      orofacial nociceptive responses.

PMID- 29042273
TI  - Leptomyxa valladaresi n. sp. (Amoebozoa, Tubulinea, Leptomyxida), from Mount
      Teide, Tenerife, Spain.
AB  - Leptomyxa valladaresi was isolated from soil in a pine forest on the southern
      flank of Mt Teide in Tenerife, Spain. It feeds on bacteria and on a range of
      other amoebae, and it was possible to establish bi-axenic cultures with L.
      valladaresi and Acanthamoeba. It is easily propagated on a E. coli also. 18S rDNA
      gene sequence analysis suggests that it is most closely related to Leptomyxa
      variabilis, however this amoeba differs in important detail. L. valladaresi is
      primarily mononucleate whereas L. variabilis is multinucleate. L. valladaresi is
      a larger amoeba and although the cysts are similar in size, there is no sign of
      the pore-like structures described in L. variabilis cysts. L. valladaresi can
      adopt a rapid monopodal and tubular morphology similar to that described for L.
      neglecta and Rhizamoeba matisi, and is never reticulated as larger L. variabilis
      individuals tend to be. The mean generation time was found to be 18 h, in line
      with amoebae of this size. Like other members of the genus, L. valladaresi is
      reported to harbour intracellular, presumably endosymbiotic bacteria, and a
      Delftia sp has been identified by 16S PCR a bacterium which is also known to grow
      within Acanthamoeba. The availability of this easily cultured species will help
      to characterize of this little studied genus and family and their relationship
      with bacteria, both prey and symbionts.

PMID- 29042274
TI  - Study of cellulose nanocrystal doped starch-polyvinyl alcohol bionanocomposite
      films.
AB  - We prepared biodegradable nanocomposites from plasticized starch-polyvinyl
      alcohol (PS-PVA) composite incorporated with cellulose nanocrystals (CNC). The
      nanocomposite films were characterized by mechanical, thermal, and barrier
      analyses as well as atomic force microscopy (AFM). The geometrical
      characteristics of the CNC confirmed that the thickness of CNC was less than
      100nm. The generated nanocomposites exhibited an improvement in mechanical and
      barrier properties. The films showed decrease in solubility, water absorption,
      water vapor permeability (WVP), and strain at break (SB). However, contact angle,
      ultimate tensile strength (UTS), glass transition temperature (Tg) and melting
      point (Tm) increased after addition of CNC. The results suggest that as a green
      reinforcement for elaboration of biodegradable packaging, CNC is a good
      replacement for mineral reinforcement such as silicates.

PMID- 29042272
TI  - Effects of dietary nitrate on respiratory physiology at high altitude - Results
      from the Xtreme Alps study.
AB  - Nitric oxide (NO) production plays a central role in conferring tolerance to
      hypoxia. Tibetan highlanders, successful high-altitude dwellers for millennia,
      have higher circulating nitrate and exhaled NO (ENO) levels than native
      lowlanders. Since nitrate itself can reduce the oxygen cost of exercise in
      normoxia it may confer additional benefits at high altitude. Xtreme Alps was a
      double-blinded randomised placebo-controlled trial to investigate how dietary
      nitrate supplementation affects physiological responses to hypoxia in 28 healthy
      adult volunteers resident at 4559 m for 1 week; 14 receiving a beetroot-based
      high-nitrate supplement and 14 receiving a low-nitrate 'placebo' of matching
      appearance/taste. ENO, vital signs and acute mountain sickness (AMS) severity
      were recorded at sea level (SL) and daily at altitude. Moreover, standard
      spirometric values were recorded, and saliva and exhaled breath condensate (EBC)
      collected. There was no significant difference in resting cardiorespiratory
      variables, peripheral oxygen saturation or AMS score with nitrate supplementation
      at SL or altitude. Median ENO levels increased from 1.5/3.0  mPa at SL, to
      3.5/7.4 mPa after 5 days at altitude (D5) in the low and high-nitrate groups,
      respectively (p = 0.02). EBC nitrite also rose significantly with dietary nitrate
      (p = 0.004), 1.7-5.1  MUM at SL and 1.6-6.3 MUM at D5, and this rise appeared to
      be associated with increased levels of ENO. However, no significant changes
      occurred to levels of EBC nitrate or nitrosation products (RXNO). Median salivary
      nitrite/nitrate concentrations increased from 56.5/786 MUM to 333/5,194  MUM 
      with nitrate supplementation at SL, and changed to 85.6/641 MUM and 341/4,553 MUM
      on D5. Salivary RXNO rose markedly with treatment at SL from 0.55 MUM to 5.70
      MUM. At D5 placebo salivary RXNO had increased to 1.90 MUM whilst treatment RXNO
      decreased to 3.26 MUM. There was no association with changes in any observation
      variables or AMS score. In conclusion, dietary nitrate supplementation is well
      tolerated at altitude and significantly increases pulmonary NO availability and
      both salivary and EBC NO metabolite concentrations. Surprisingly, this is not
      associated with changes in hemodynamics, oxygen saturation or AMS development.

PMID- 29042275
TI  - Basil polysaccharide attenuates hepatocellular carcinoma metastasis in rat by
      suppressing H3K9me2 histone methylation under hepatic artery ligation-induced
      hypoxia.
AB  - Hepatocellular carcinoma (HCC) is one of the most common and fatal cancers in the
      world. Tumor metastasis is an important factor of poor prognosis in patients with
      HCC. Tumor hypoxia can promote tumor cell metastasis in HCC. Epigenetic
      modification is closely related to tumor hypoxia and metastasis. In our previous
      research, we found that basil polysaccharide suppressed migration and invasion of
      HCC cell by inhibiting hypoxia induced histone methylation in vitro. In the
      present study, we investigated the effect of basil polysaccharide on the walker
      256 carcinoma cell metastasis in rat. We established an intratumoral hypoxic
      model in rat by hepatic artery ligation (HAL). Then rats were treated with basil
      polysaccharide (75, 150 and 300mg/kg). The results showed that HAL could promote
      tumor metastasis by aggravating tumor hypoxia. However, basil polysaccharide
      could inhibit tumor metastasis in intratumoral hypoxia. Further, we demonstrated
      that basil polysaccharide could down-regulate the expression of HIF-1alpha, G9a,
      LSD1, JMJD1A, JMJD2B, JARID1B and H3K9me2. Synchronously, basil polysaccharide
      could increase E-cadherin and VMP1 expression, and decrease N-cadherin, vimentin
      and beta-catenin expression. The results indicated that histone modifying enzymes
      might be a new therapeutic target of basil polysaccharide on hepatocellular
      carcinoma metastasis.

PMID- 29042276
TI  - Heterologous expression of an engineered protein domain acts as chaperone and
      enhances thermotolerance of Escherichia coli.
AB  - Heat shock proteins (HSPs) are known to confer protection to the stressed cells
      by rescuing vital host cell proteins. In the present study we have demonstrated
      that heterologous expression of N-terminal domain of hyperthermophilic L
      asparaginase (NPfA) confers thermotolerance to E. coli. The recombinant
      expression of NPfA enabled E. coli to demonstrate typical growth behavior at 52
      degrees C and survive a thermal shock up to 62 degrees C, both being the highest
      reported temperatures for growth and heat shock survival. To understand the basis
      of protection proteome analysis of these cells was carried out which showed that
      NPfA guards a battery of proteins, especially related to gene regulations and
      repair, providing definite survival advantage to the stressed cells. Thus NPfA a
      non-canonical, non-natural chaperone has been shown to render E. coli cells with
      selective growth advantage under extremes of conditions. We propose that such
      modified, heat stabilized hosts could be utilized in developing heat-induced
      expression systems as well for the recombinant expression of thermophilic
      proteins.

PMID- 29042277
TI  - MiR-455-3p activates Nrf2/ARE signaling via HDAC2 and protects osteoblasts from
      oxidative stress.
AB  - BACKGROUND: The important role of miR-455-3p in the pathogenesis of bone
      metabolism associated diseases is gradually emerging. This study aims to
      ascertain the involvement of miR-455-3p and its underlying mechanisms in
      osteoporosis. METHODS: The osteoblast cell lines MC3T3-E1 was treated with ferric
      ammonium citrate (FAC) to mimic a pathological environment for osteoporosis. The
      cytotoxic effect of iron overload was assessed by proliferation, apoptosis and
      oxidative stress of osteoblasts using commercial kits. Molecular biological
      methods, including qRT-PCR analysis, cell transfection and luciferase reporter
      assays were used to explain the role of miR-455-3p and its potential mechanisms
      in osteoblast apoptosis. RESULTS: FAC dramatically inhibited the proliferation of
      osteoblast cells MC3T3-E1 but increased the apoptosis. We also observed that FAC
      significantly down-regulated miR-455-3p in MC3T3-E1 cells but enhanced HDAC2
      protein level. Moreover, miR-455-3p overexpression eliminated the effects of iron
      overload on osteoblast cell proliferation, apoptosis and oxidative stress. In
      addition, miR-455-3p regulated osteoblast cell proliferation, apoptosis and
      oxidative stress through regulating HDAC2-Nrf2/ARE signaling pathway. MiR-455-3p
      overexpression alleviated the oxidative stress injury in osteoporosis mice.
      CONCLUSION: Our results demonstrated that miR-455-3p activated Nrf2/ARE signal
      pathway through suppressing Keap1 via negative regulating HDAC2 protein level,
      thereby suppressing oxidative stress and promoting osteoblasts growth.

PMID- 29042278
TI  - A ribonuclease inhibitor resistant dimer of human pancreatic ribonuclease
      displays specific antitumor activity.
AB  - Human pancreatic ribonuclease (HPR) and bovine seminal ribonuclease (BS-RNase)
      are members of the RNase A superfamily. HPR is monomeric, whereas BS-RNase is
      dimeric. BS-RNase has strong antitumor and cytotoxic activities. However, HPR
      lacks cytotoxic activity as it is inactivated by intracellular cytosolic
      ribonuclease inhibitor (RI). Earlier, an RI-resistant cytotoxic variant of HPR,
      termed HPR-KNE was generated which contained three residues Lys7, Asn71 and
      Glu111 of HPR, known to interact with RI, mutated to alanine. In this study, we
      have engineered HPR to develop two dimeric RI-resistant molecules having anti
      tumor activity. By incorporating two cysteines in HPR and HPR-KNE, we generated
      disulfide linked dimeric HPR, and a dimer of HPR-KNE, termed as HPR-D and HPR-KNE
      D respectively. HPR-KNE-D was resistant towards inhibition by RI, and was found
      to be highly toxic to a variety of cells. On J774A.1 cells HPR-KNE-D was >375
      fold more cytotoxic than HPR, and 15-fold more toxic than HPR-D. Further, on U373
      cells HPR-KNE-D was >65-fold more cytotoxic than HPR, and 9-fold more toxic than
      HPR-D. The study demonstrates that combining dimerization and RI-resistance
      results in providing potent anti-tumor activity to HPR. The cytotoxic variants of
      HPR will be useful in designing protein therapeutics with low immunogenicity.

PMID- 29042279
TI  - Long circulating PEGylated-chitosan nanoparticles of rosuvastatin calcium:
      Development and in vitro and in vivo evaluations.
AB  - The aim of this study was to improve the pharmacokinetics and pharmacodynamics
      profile of rosuvastatin calcium by formulating long-circulating PEGylated
      chitosan nanoparticles (NPs). Chitosan was PEGylated by a carbodiimide mediated
      reaction, using a carboxylic acid derivative of PEG (polyethylene glycol). The
      NPs were optimised for particle size, polydispersity index, zeta potential and
      drug entrapment efficiency. In vitro drug release, pharmacokinetic and
      pharmacodynamics studies of the optimized nanoparticles were performed.
      PEGylation of chitosan was confirmed by FTIR analysis. Drug-excipient
      compatibility was studied by differential scanning calorimetry and FTIR analyses.
      Two batches of nanoparticles were optimized with particle size of <200nm and
      entrapment efficiency of ~14%. In vitro drug release studies revealed cumulative
      release of 14.07+/-0.57% and 22.02+/-0.81% of rosuvastatin over the period of
      120h, indicating appreciable sustained release of drug. TEM analysis showed the
      spherical structure of nanoparticles. Pharmacokinetic studies indicated that
      optimized NPs showed prolonged drug release over a period of 72h.
      Pharmacodynamics studies in hyperlipidemic rat model demonstrated greater lipid
      lowering capability of rosuvastatin nanoparticles in comparison with plain
      rosuvastatin. The nanoparticles demonstrated substantial prolonged delivery of
      the drug in vivo along with better therapeutic action, which could be potential
      drug delivery modality for 'statins'.

PMID- 29042280
TI  - Biochemical and biophysical characterization of a mycoredoxin protein
      glutaredoxin A1 from Corynebacterium pseudotuberculosis.
AB  - Glutaredoxin A1 from Corynebacterium pseudotuberculosis was shown to be a
      mycoredoxin protein. In this study, we established a process to overexpress and
      purify glutaredoxin A1. The aim of this study was the investigation of the
      Glutaredoxin A1 from C. pseudotuberculosis behavior under different redox
      environments and the identification of lead molecules, which can be used for
      specific inhibitor development for this protein family. A quantitative assay was
      performed measuring the rate of insulin reduction spectrophotometrically at 640nm
      through turbidity formation from the precipitation of the free insulin.
      Glutaredoxin A1, at 5MUM concentration, accelerated the reduction process of
      0.2mM insulin and 1mM DTT. The pH optimum of the reaction was 7.4. In the
      presence of DTT and ESH the glutaredoxin A1 presents similar activity, and its
      activity is reduced by 50% in the presence of GSH. Additional function for ESH in
      the redox metabolism of C. pseudotuberculosis is suggested. A combined STD and
      Chemical Shift - NMR approach was employed to study the effects of potential
      inhibitors on the structure of glutaredoxin A1 from Corynebacterium
      pseudotuberculosis. The inhibitory potential of four ligands (heparin, suramin,
      hesperetin - Hst, and hesperidin - Hsp) against glutaredoxin A1 is discussed.

PMID- 29042281
TI  - Effects of polysaccharides from the base of Flammulina Velutipes stipe on growth
      of murine RAW264.7, B16F10 and L929 cells.
AB  - A polysaccharide (FVSP) was isolated from the base of Flammuliana Velutipes
      stipe, and FVSP was further purified by DEAE-cellulose-52 chromatography and
      Sephadex G-100 size-exclusion chromatography to obtain three fractions named FVSP
      1, FVSP-2 and FVSP-3. Then their activation of macrophage cell RAW 264.7 and anti
      proliferative effects to the murine melanoma B16F10 and fibroblasts L929 cells
      were evaluated by using the cell model experiments. The results indicated that
      the polysaccharide fractions could increase the proliferation and phagocytic
      activity of macrophage significantly and play an inhibited effect on the cancer
      cells. Moreover, the anti-proliferative activities of FVSPs increased with the
      participation of the antitumor factors induced from macrophage by polysaccharides
      fractions. Taken together, these results indicated that three polysaccharides
      fractions from the base of F. Velutipes stipe may be useful as potent antitumor
      agents for the prevention of tumorigenesis.

PMID- 29042282
TI  - Increased levels of circulating (TNF-alpha) is associated with (-308G/A) promoter
      polymorphism of TNF-alpha gene in Diabetic Nephropathy.
AB  - The crucial role of Tumor Necrosis Factor-alpha (TNF-alpha) on renal function in
      patients with Diabetic Nephropathy (DN) has been well documented. The present
      study was designed to investigate the association of TNF-alpha [-308G/A,
      (rs1800629)] single nucleotide polymorphism (SNP) on the susceptibility to DN
      subjects and to correlate it with the plasma levels of TNF-alpha along with
      circulatory TNF-alpha receptor super family cytokines (sTNFR-1 and sTNFR-2). A
      total of 756 subjects, were recruited and divided into groups [Group-I, Control
      (n=218), Group-II, Normoalbuminuria (n=196), Group-IIIa, Microalbuminuria
      (n=178), Group-IIIb, Macroalbuminuria (n=164)] and were genotyped by PCR
      restriction fragment length polymorphism (RFLP). Circulatory levels of TNF-alpha
      and sTNFR-1 & sTNFR-2 were measured using multiplex bead based assay. The 'A'
      allele of TNF-alpha (-308 G/A) SNP was associated with a significant risk for
      macroalbuminuria subjects (OR: 2.1; 95% CI: 0.8-3.7; P<0.001). A marked stepwise
      increase was observed in the levels of circulatory biomarkers such as TNF-alpha,
      sTNF-R1 and sTNF-R2 from normo to macroalbuminuria subjects. In DN subjects, the
      TNF-alpha level was higher in individuals who had mutant AA, than the wild GG
      genotype of TNF-alpha gene. Our results conclude that rs1800629 polymorphism in
      TNF-alpha gene is associated with renal complications in T2DM subjects.

PMID- 29042283
TI  - The PR-1 domain accounts for the anti-angiogenic activity of a cysteine-rich
      secretory protein member from the buccal glands of Lampetra japonica.
AB  - Previous studies have shown that cysteine-rich buccal gland protein (CRBGP) from
      buccal glands of Lampetra japonica could suppress angiogenesis in chick
      chorioallantoic membrane models. As CRBGP is composed of a pathogenesis-related
      group 1 (PR-1) domain and a cysteine-rich domain (CRD), which domain accounts for
      the effects of CRBGP on anti-angiogenesis? In the present study, recombinant PR-1
      and CRD (rL-PR-1 and rL-CRD) were obtained. MTT assays showed rL-PR-1 inhibited
      the proliferation of HUVECs significantly in a dose-dependent manner with an IC50
      of 2MUM, while rL-CRD had no obviously inhibitory effect on the proliferation of
      HUVECs, suggested that PR-1 is the main function domain on the anti-angiogenic
      activity of CRBGP. Similar to CRBGP, rL-PR-1 induced apoptosis in HUVECs in a
      mitochondrial-dependent pathway by affecting the level of BAX, BCL2 and caspase
      3. Also, the cytotoxic property of rL-PR-1 might be one of the factors which
      suppressed the proliferation of HUVECs. Furthermore, rL-PR-1 blocked the
      adhesion, migration, invasion and tube formation of HUVECs by disturbing the
      cytoskeleton arrangement and down-regulating the level of matrix metallo
      peptidase 2. In summary, rL-PR-1 has the anti-angiogenic activity which would
      provide the information on the functions and mechanisms of cysteine-rich
      secretory protein family members.

PMID- 29042284
TI  - The synergism and attenuation effect of Selenium (Se)-enriched Grifola frondosa
      (Se)-polysaccharide on 5-Fluorouracil (5-Fu) in Heps-bearing mice.
AB  - Previous study revealed that Se-GP11 could exhibited its antitumor activity by
      improving the immune functions. 5-Fu, as a chemotherapeutic drugs, can kill many
      immune cells in addition to tumor cells. Accordingly, the enhanced antitumor and
      reduced toxicity of Se-GP11 on 5-Fu were estimated in this study. The results
      demonstrated that Se-GP11 could evidently increase the antitumor activity of 5
      Fu. Furthermore, Se-GP11 could enhance the immune functions during the tumor
      inhibition process of 5-Fu for increasing the cytokines secretion (IL-2 and TNF
      alpha) and immune organs weights. In addition, Se-GP11 could reduce the toxicity
      of 5-Fu on liver by improving the hematological and biochemical parameters and up
      regulating the SOD activities and down-regulating the MDA levels. Taken together,
      the results indicated that Se-GP11 may develop as an auxiliary preparation to
      chemical antitumor drugs.

PMID- 29042287
TI  - The genus Lycium as food and medicine: A botanical, ethnobotanical and historical
      review.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Lycium is widely distributed in the arid to semi
      arid environments of North and South America, Africa, and Eurasia. In recent
      years, Lycium barbarum and L. chinense have been advertised as "superfood" with
      healthy properties. Despite of its popularity, there is a lack of an integrated
      and critical appraisal of the existing evidence for the use of Lycium. AIM OF THE
      STUDY: There is a need to understand: 1) Which species were used and how the uses
      of Lycium developed spatially and over time, 2) how uses differ among regions
      with different culture backgrounds, and 3) how traditional and current
      therapeutic and preventive health claims correlate with pharmacological findings.
      METHODS: Information was retrieved from floras, taxonomic, botanical, and
      ethnobotanical databases, research articles, recent editions of historical
      Chinese herbals over the last 2000 years, and pharmacopoeias. RESULTS: Of totally
      97 species, 31 have recorded uses as food and/or medicine worldwide. Usually the
      fruits are used. While 85% of the Lycium species occur in the Americas and
      Africa, 26% of them are used, but 9 out of 14 species in Eurasia. In China, seven
      species and two varieties of the genus Lycium occur, of which four species have
      been used by different ethnic groups. Only L. barbarum and L. chinense have been
      transformed into globally traded commodities. In China, based on the name "",
      their use can be traced back over the last two millennia. Lycium fruits for anti
      aging, improving eyesight and nourishment were documented already in 500C.E.
      (Mingyi Bielu). Recent findings explain the pharmacological foundations of the
      traditional uses. Especially polysaccharides, zeaxanthin dipalmitate, vitamins,
      betaine, and mixed extracts were reported to be responsible for anti-aging,
      improving eyesight, and anti-fatigue effects. CONCLUSIONS: The integration of
      historical, ethnobotanical, botanical, phytochemical and pharmacological data has
      enabled a detailed understanding of Lycium and its wider potential. It highlights
      that the focus so far has only been on two species and that the genus can
      potentially yield a wide range of other products with different properties.

PMID- 29042285
TI  - Regulating the regulators: Epigenetic, transcriptional, and post-translational
      regulation of RGS proteins.
AB  - Regulators of G protein signaling (RGS) are a family of proteins classically
      known to accelerate the intrinsic GTPase activity of G proteins, which results in
      accelerated inactivation of heterotrimeric G proteins and inhibition of G protein
      coupled receptor signaling. RGS proteins play major roles in essential cellular
      processes, and dysregulation of RGS protein expression is implicated in multiple
      diseases, including cancer, cardiovascular and neurodegenerative diseases. The
      expression of RGS proteins is highly dynamic and is regulated by epigenetic,
      transcriptional and post-translational mechanisms. This review summarizes studies
      that report dysregulation of RGS protein expression in disease states, and
      presents examples of drugs that regulate RGS protein expression. Additionally,
      this review discusses, in detail, the transcriptional and post-transcriptional
      mechanisms regulating RGS protein expression, and further assesses the
      therapeutic potential of targeting these mechanisms. Understanding the molecular
      mechanisms controlling the expression of RGS proteins is essential for the
      development of therapeutics that indirectly modulate G protein signaling by
      regulating expression of RGS proteins.

PMID- 29042286
TI  - Protein kinase- and lipase inhibitors of inositide metabolism deplete IP7
      indirectly in pancreatic beta-cells: Off-target effects on cellular bioenergetics
      and direct effects on IP6K activity.
AB  - Inositol pyrophosphates have emerged as important regulators of many critical
      cellular processes from vesicle trafficking and cytoskeletal rearrangement to
      telomere length regulation and apoptosis. We have previously demonstrated that 5
      di-phosphoinositol pentakisphosphate, IP7, is at a high level in pancreatic beta
      cells and is important for insulin exocytosis. To better understand IP7
      regulation in beta-cells, we used an insulin secreting cell line, HIT-T15, to
      screen a number of different pharmacological inhibitors of inositide metabolism
      for their impact on cellular IP7. Although the inhibitors have diverse targets,
      they all perturbed IP7 levels. This made us suspicious that indirect, off-target
      effects of the inhibitors could be involved. It is known that IP7 levels are
      decreased by metabolic poisons. The fact that the inositol hexakisphosphate
      kinases (IP6Ks) have a high Km for ATP makes IP7 synthesis potentially vulnerable
      to ATP depletion. Furthermore, many kinase inhibitors are targeted to the ATP
      binding site of kinases, but given the similarity of such sites, high specificity
      is difficult to achieve. Here, we show that IP7 concentrations in HIT-T15 cells
      were reduced by inhibitors of PI3K (wortmannin, LY294002), PI4K (Phenylarsine
      Oxide, PAO), PLC (U73122) and the insulin receptor (HNMPA). Each of these
      inhibitors also decreased the ATP/ADP ratio. Thus reagents that compromise energy
      metabolism reduce IP7 indirectly. Additionally, PAO, U73122 and LY294002 also
      directly inhibited the activity of purified IP6K. These data are of particular
      concern for those studying signal transduction in pancreatic beta-cells, but also
      highlight the fact that employment of these inhibitors could have erroneously
      suggested the involvement of key signal transduction pathways in various cellular
      processes. Conversely, IP7's role in cellular signal transduction is likely to
      have been underestimated.

PMID- 29042289
TI  - Current evidence on the effect of dietary polyphenols intake on chronic diseases.
AB  - Polyphenols are secondary metabolites of plants. They comprise several
      antioxidant compounds and they are generally considered to be involved in the
      defense against human chronic diseases. During the last years, there has been
      growing scientific interest in their potential health benefits. In this
      comprehensive review, we focus on the current evidence defining the position of
      their dietary intake in the prevention/treatment of human chronic diseases,
      including prostate cancer and other types of cancer, cardiovascular diseases,
      diabetes mellitus and neurodegenerative diseases such as Alzheimer's and
      Parkinson's disease; we also discuss their ability to modulate multiple
      signalling transduction pathways involved in the pathophysiology of these
      diseases. Despite the fact that data regarding the biological functions of
      polyphenols can be considered exhaustive, evidence is still inadequate to support
      clear beneficial effects on human chronic diseases. Currently, most data suggest
      that a combination of phytochemicals rather than any single polyphenol is
      responsible for health benefit. More studies investigating the role of
      polyphenols in the prevention of chronic human diseases are needed, especially
      for evaluating factors such as gender, age, genotype, metabolism and
      bioavailability.

PMID- 29042288
TI  - Mast cell degranulation and calcium influx are inhibited by an Echinacea purpurea
      extract and the alkylamide dodeca-2E,4E-dienoic acid isobutylamide.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Native Americans used plants from the genus
      Echinacea to treat a variety of different inflammatory conditions including
      swollen gums, sore throats, skin inflammation, and gastrointestinal disorders.
      Today, various Echinacea spp. preparations are used primarily to treat upper
      respiratory infections. AIM OF THE STUDY: The goal of this study was to evaluate
      the effects of an ethanolic E. purpurea (L) Moench root extract and the
      alkylamide dodeca-2E,4E-dienoic acid isobutylamide (A15) on mast cells, which are
      important mediators of allergic and inflammatory responses. Inhibition of mast
      cell activation may help explain the traditional use of Echinacea. MATERIALS AND
      METHODS: A15 was evaluated for its effects on degranulation, calcium influx,
      cytokine and lipid mediator production using bone marrow derived mast cells
      (BMMCs) and the transformed rat basophilic leukemia mast cell line RBL-2H3.
      Methods included enzymatic assays, fluorimetry, ELISAs, and microscopy. A root
      extract of E. purpurea, and low and high alkylamide-containing fractions prepared
      from this extract, were also tested for effects on mast cell function. Finally,
      we tested A15 for effects on calcium responses in RAW 264.7 macrophage and Jurkat
      T cell lines. RESULTS: A15 inhibited beta-hexosaminidase release from BMMCs and
      RBL-2H3 cells after treatment with the calcium ionophore A23187 by 83.5% and
      48.4% at 100uM, respectively. Inhibition also occurred following stimulation with
      IgE anti-DNP/DNP-HSA. In addition, A15 inhibited 47% of histamine release from
      A23187-treated RBL-2H3 cells. A15 prevented the rapid rise in intracellular
      calcium following FcepsilonRI crosslinking and A23187 treatment suggesting it
      acts on the signals controlling granule release. An E. purpurea root extract and
      a fraction with high alkylamide content derived from this extract also displayed
      these activities while fractions with little to no detectable amounts of
      alkylamide did not. A15 mediated inhibition of calcium influx was not limited to
      mast cells as A23187-stimulated calcium influx was blocked in both RAW 264.7 and
      Jurkat cell lines with 60.2% and 43.6% inhibition at 1min post-stimulation,
      respectively. A15 also inhibited the release of TNF-alpha, and PGE2 to a lesser
      degree, following A23187 stimulation indicating its broad activity on mast cell
      mediator production. CONCLUSIONS: These findings suggest that Echinacea extracts
      and alkylamides may be useful for treating allergic and inflammatory responses
      mediated by mast cells. More broadly, since calcium is a critical second
      messenger, the inhibitory effects of alkylamides on calcium uptake would be
      predicted to dampen a variety of pathological responses, suggesting new uses for
      this plant and its constituents.

PMID- 29042290
TI  - Wild edible plants: Nutritional and toxicological characteristics, retrieval
      strategies and importance for today's society.
AB  - Wild edible plants (WEPs) are part of the cultural and genetic heritage of
      different regions of the world. In times of famine and scarcity, these sources of
      nutrients and health-promoting compounds have received high importance mainly in
      rural and suburban areas. Although currently underutilized, WEPs are still
      consumed traditionally by different communities and are gaining relevance in
      today's society. However, these foods lack recognition as significant
      contributors to the human diet in developed areas. This review describes the
      nutritional value of WEPs from the North-eastern region of Portugal and points
      out those containing potentially toxic compounds. Several retrieval strategies
      are presented with the aim of promoting the (re)use, production,
      commercialization and conservation of WEPs (wild harvested plants and crop wild
      relatives), and their importance for social, economic and agro-ecological
      development is highlighted.

PMID- 29042291
TI  - MicroRNAs as biomarkers for liver injury: Current knowledge, challenges and
      future prospects.
AB  - MicroRNAs (miRNAs) are short regulatory RNAs that are involved in various
      biological processes that regulate gene expression posttranscriptionally. Changes
      in miRNA expression can be detected in many physiological and pathological
      events, such as liver injury. Drug induced liver injury is a life threatening
      condition that frequently requires organ transplantation. Hepatotoxicity is also
      one of the major causes of drug failure in clinical trials and of drug withdrawal
      from the market. The profiling of miRNA expression shows great promise in
      monitoring liver injury, in the prediction of outcome in patients, and in the
      identification of liver-reactive compounds in toxicological assessment. Recent
      studies have demonstrated organ-specificity of some miRNAs (i.e., miR-122), which
      are released into biological fluids as a result of hepatocyte damage. This
      attests to the potential of miRNAs as noninvasive biomarkers to detect liver
      toxicity. This review presents information on miRNA signatures of hepatotoxicity
      and on the application of promising miRNA biomarkers in preclinical safety
      assessment. We further discuss the technical challenges associated with these
      emerging biomarkers for early diagnosis and detection of hepatotoxicity.

PMID- 29042292
TI  - Obesity enhances carcinogen 7, 12-Dimethylbenz [a] anthracene -induced
      tumorigenesis in vitro and in vivo.
AB  - Growing body of evidence shows that extra adiposity influences on the progression
      of multiple cancers, including breast cancer. The aim of this study is to
      investigate whether obesity correlates with mammary tumor development in vitro
      and in vivo. We found that obesity-related mediators, 3T3-L1 adipocyte
      conditioned medium, enhanced formation of cancerous foci induced by the
      carcinogen 7,12-Dimethylbenz[a]anthracene (DMBA) in NIH/3T3 fibroblasts, in
      vitro. Additionally, we tested the effect of obesity in mouse model of DMBA
      induced breast cancer. C57BL/6J female mice were fed a low fat (LF), or high fat
      (HF) diet, and DMBA was administered by oral gavage (LF plus DMBA [LFD] and HF
      plus DMBA [HFD]). Our results indicated that HFD mouse developed a tumor which
      weight was 169mg, whereas the LFD mouse developed a tumor weight of 77mg.
      Histological analysis of the mammary tumor from HFD group showed morphological
      aggressiveness and multiple cell type infiltration compared to LFD group. The
      epididymal adipose tissue from the DMBA groups showed more macrophage
      infiltration, polarized towards an M1 phenotype compared to the non-DMBA mice. HF
      mice showed less accumulation of M2 macrophages in the adipose tissue. In
      summary, obese mediators enhanced DMBA induced tumorigenesis in vitro and in
      vivo.

PMID- 29042293
TI  - Development of novel prediction model for drug-induced mitochondrial toxicity by
      using naive Bayes classifier method.
AB  - Mitochondrial dysfunction has been considered as an important contributing factor
      in the etiology of drug-induced organ toxicity, and even plays an important role
      in the pathogenesis of some diseases. The objective of this investigation was to
      develop a novel prediction model of drug-induced mitochondrial toxicity by using
      a naive Bayes classifier. For comparison, the recursive partitioning classifier
      prediction model was also constructed. Among these methods, the prediction
      performance of naive Bayes classifier established here showed best, which yielded
      average overall prediction accuracies for the internal 5-fold cross validation of
      the training set and external test set were 95 +/- 0.6% and 81 +/- 1.1%,
      respectively. In addition, four important molecular descriptors and some
      representative substructures of toxicants produced by ECFP_6 fingerprints were
      identified. We hope the established naive Bayes prediction model can be employed
      for the mitochondrial toxicity assessment, and these obtained important
      information of mitochondrial toxicants can provide guidance for medicinal
      chemists working in drug discovery and lead optimization.

PMID- 29042294
TI  - Impaired cardiac autonomic regulation and long-term risk of atrial fibrillation
      in patients with coronary artery disease.
AB  - BACKGROUND: The influence of autonomic cardiac regulation on long-term risk of
      new-onset atrial fibrillation (AF) in coronary artery disease (CAD) is not well
      established. OBJECTIVE: The purpose of this study was to evaluate the value of
      heart rate variability, a marker of cardiac autonomic regulation, in predicting
      new-onset AF in CAD. METHODS: The Innovation to Reduce Cardiovascular
      Complications of Diabetes at the Intersection study population consisted of 1946
      patients with CAD. After exclusions, the present analysis included 1710 patients.
      Those patients had a 24-hour electrocardiographic recording at baseline. RESULTS:
      A total of 143 cases (8.4%) of new-onset AF were observed during a follow-up of
      5.6 +/- 1.5 years. The lower values of the short-term scaling exponent of the
      detrended fluctuation analysis (DFA1) and the ratio of the low-frequency and high
      frequency components of the power spectrum (LF/HF ratio) remained the strongest
      heart rate variability predictors of the development of AF after relevant
      adjustments in Cox multivariate regression analysis (P < .001 for both). The
      accuracy of these parameters in prediction of AF was even better (area under the
      receiver operating characteristic curve 0.630 and 0.631, respectively) than that
      of echocardiographic left atrial diameter (area under the curve 0.618). Including
      DFA1 and LF/HF ratio in the AF risk model increased the C-index from 0.630 (95%
      confidence interval 0.569-0.692) to 0.666 (95% confidence interval 0.612-0.720).
      CONCLUSION: Impaired cardiac autonomic regulation measured by DFA1 and LF/HF
      ratio predicts the development of new-onset AF as well as or even better than
      left atrial diameter in patients with CAD.

PMID- 29042295
TI  - Chronic obstructive pulmonary disease and ventricular arrhythmia-Association or
      causation?

PMID- 29042296
TI  - Computations in the deep vs superficial layers of the cerebral cortex.
AB  - A fundamental question is how the cerebral neocortex operates functionally,
      computationally. The cerebral neocortex with its superficial and deep layers and
      highly developed recurrent collateral systems that provide a basis for memory
      related processing might perform somewhat different computations in the
      superficial and deep layers. Here we take into account the quantitative
      connectivity within and between laminae. Using integrate-and-fire neuronal
      network simulations that incorporate this connectivity, we first show that
      attractor networks implemented in the deep layers that are activated by the
      superficial layers could be partly independent in that the deep layers might have
      a different time course, which might because of adaptation be more transient and
      useful for outputs from the neocortex. In contrast the superficial layers could
      implement more prolonged firing, useful for slow learning and for short-term
      memory. Second, we show that a different type of computation could in principle
      be performed in the superficial and deep layers, by showing that the superficial
      layers could operate as a discrete attractor network useful for categorisation
      and feeding information forward up a cortical hierarchy, whereas the deep layers
      could operate as a continuous attractor network useful for providing a spatially
      and temporally smooth output to output systems in the brain. A key advance is
      that we draw attention to the functions of the recurrent collateral connections
      between cortical pyramidal cells, often omitted in canonical models of the
      neocortex, and address principles of operation of the neocortex by which the
      superficial and deep layers might be specialized for different types of attractor
      related memory functions implemented by the recurrent collaterals.

PMID- 29042297
TI  - TREK-1 pathway mediates isoflurane-induced memory impairment in middle-aged mice.
AB  - Post-operative cognitive dysfunction (POCD) has been widely reported, especially
      in elderly patients. An association between POCD and inhalational anesthetics,
      such as isoflurane, has been suggested. The TWIK-related K+ channel-1 (TREK-1)
      controls several major cellular responses involved in memory formation and is
      believed to participate in the development of depression, cerebral ischemia and
      blood-brain barrier dysfunction. However, the specific role of TREK-1 in
      mediating anesthesia-induced POCD remains unknown. In the current study, we
      determined that exposure to isoflurane affected memory in middle-aged mice and
      altered TREK-1 expression. In addition, TREK-1 over-expression exacerbated
      isoflurane-induced memory impairment, while TREK-1 silence attenuated the
      impairment. Taken together, our data demonstrate that inhibition of TREK-1
      protects mice from cognitive impairment induced by anesthesia and TREK-1 is a
      potential therapeutic target against memory impairment induced by volatile
      anesthetics.

PMID- 29042299
TI  - Non-pharmacological interventions for spasticity in adults: An overview of
      systematic reviews.
AB  - OBJECTIVES: Spasticity causes significant long-term disability-burden, requiring
      comprehensive management. This review evaluates evidence from published
      systematic reviews of clinical trials for effectiveness of non-pharmacological
      interventions for improved spasticity outcomes. METHODS: Data sources: a
      literature search was conducted using medical and health science electronic
      (MEDLINE, EMBASE, CINAHL, PubMed, and the Cochrane Library) databases for
      published systematic reviews up to 15th June 2017. DATA EXTRACTION AND SYNTHESIS:
      two reviewers applied inclusion criteria to select potential systematic reviews,
      independently extracted data for methodological quality using Assessment of
      Multiple Systematic Reviews (AMSTAR). Quality of evidence was critically
      appraised with Grades of Recommendation, Assessment, Development and Evaluation
      (GRADE). RESULTS: Overall 18 systematic reviews were evaluated for evidence for a
      range of non-pharmacological interventions currently used in managing spasticity
      in various neurological conditions. There is "moderate" evidence for electro
      neuromuscular stimulation and acupuncture as an adjunct therapy to conventional
      routine care (pharmacological and rehabilitation) in persons following stroke.
      "Low" quality evidence for rehabilitation programs targeting spasticity (such as
      induced movement therapy, stretching, dynamic elbow-splinting, occupational
      therapy) in stroke and other neurological conditions; extracorporeal shock-wave
      therapy in brain injury; transcranial direct current stimulation in stroke;
      transcranial magnetic stimulation and transcutaneous electrical nerve stimulation
      for other neurological conditions; physical activity programs and repetitive
      magnetic stimulation in persons with MS, vibration therapy for SCI and stretching
      for other neurological condition. For other interventions, evidence was
      inconclusive. CONCLUSIONS: Despite the available range of non-pharmacological
      interventions for spasticity, there is lack of high-quality evidence for many
      modalities. Further research is needed to judge the effect with appropriate study
      designs, timing and intensity of modalities, and associate costs of these
      interventions.

PMID- 29042298
TI  - Metabolism of the fast-growing bacterium Vibrio natriegens elucidated by 13C
      metabolic flux analysis.
AB  - Vibrio natriegens is a fast-growing, non-pathogenic bacterium that is being
      considered as the next-generation workhorse for the biotechnology industry.
      However, little is known about the metabolism of this organism which is limiting
      our ability to apply rational metabolic engineering strategies. To address this
      critical gap in current knowledge, here we have performed a comprehensive
      analysis of V. natriegens metabolism. We constructed a detailed model of V.
      natriegens core metabolism, measured the biomass composition, and performed high
      resolution 13C metabolic flux analysis (13C-MFA) to estimate intracellular fluxes
      using parallel labeling experiments with the optimal tracers [1,2-13C]glucose and
      [1,6-13C]glucose. During exponential growth in glucose minimal medium, V.
      natriegens had a growth rate of 1.70 1/h (doubling time of 24min) and a glucose
      uptake rate of 3.90g/g/h, which is more than two 2-fold faster than E. coli,
      although slower than the fast-growing thermophile Geobacillus LC300. 13C-MFA
      revealed that the core metabolism of V. natriegens is similar to that of E. coli,
      with the main difference being a 33% lower normalized flux through the oxidative
      pentose phosphate pathway. Quantitative analysis of co-factor balances provided
      additional insights into the energy and redox metabolism of V. natriegens. Taken
      together, the results presented in this study provide valuable new information
      about the physiology of V. natriegens and establish a solid foundation for future
      metabolic engineering efforts with this promising microorganism.

PMID- 29042300
TI  - Pregnancy-related low back pain in women in Turkey: Prevalence and risk factors.
AB  - OBJECTIVES: To investigate the prevalence of pregnancy-related low back pain
      (PRLBP) in women in Turkey, identify the factors associated with PRLBP and
      predict the risk of PRLBP. MATERIALS AND METHODS: This cross-sectional study
      included a total of 1500 pregnant women admitted to a prenatal care clinic in a
      secondary care hospital in Turkey between August 2011 and September 2014. All
      participants were asked to complete a survey questionnaire. The pregnant women
      who reported recurrent or continuous pain in the lumbar spine or pelvis for more
      than 1 week were offered a clinical examination for PRLBP by the spine
      physiatrist. The main outcome measure was the presence of PRLBP. We collected
      data on sociodemographic factors, previous obstetric history, daily habits,
      history of LBP, and functional disability scores as assessed by the Oswestry
      Disability Index (ODI). RESULTS: The mean age of the 1500 women was 26.5+/-5.5
      years. The prevalence of PRLBP was 53.9%, mostly in the third trimester. Women
      with PRLBP in the third trimester were more disabled than those in the first and
      second trimesters (mean ODI 40.0+/-16.7 vs. 34.9+/-19.2 and 37.4+/-15.3,
      respectively). Risk factors of PRLBP were history of LBP, PRLBP, and menstruation
      related LBP as well as no housework assistance (OR=5.394, 95% CI: 3.128-9.300,
      P<0.001; 3.692, 2.745-4.964, P<0.001; 2.141, 1.563-2.932, P<0.001; 1.300, 1.029
      1.64, P=0.028, respectively). CONCLUSION: This cross-sectional study is the
      largest study of PRLBP in the literature and showed that about 1 in 2 women have
      PRLBP in any stage of pregnancy. History of LBP related and unrelated to previous
      pregnancy and menstruation are strong risk factors for PRLBP. Receiving no
      housework assistance is another risk factor.

PMID- 29042301
TI  - Towards a first implementation of the WLIMES approach in living system studies
      advancing the diagnostics and therapy in augmented personalized medicine.
AB  - The goal of this paper is to advance an extensible theory of living systems using
      an approach to biomathematics and biocomputation that suitably addresses self
      organized, self-referential and anticipatory systems with multi-temporal multi
      agents. Our first step is to provide foundations for modelling of emergent and
      evolving dynamic multi-level organic complexes and their sustentative processes
      in artificial and natural life systems. Main applications are in life sciences,
      medicine, ecology and astrobiology, as well as robotics, industrial automation,
      man-machine interface and creative design. Since 2011 over 100 scientists from a
      number of disciplines have been exploring a substantial set of theoretical
      frameworks for a comprehensive theory of life known as Integral Biomathics. That
      effort identified the need for a robust core model of organisms as dynamic
      wholes, using advanced and adequately computable mathematics. The work described
      here for that core combines the advantages of a situation and context aware
      multivalent computational logic for active self-organizing networks, Wandering
      Logic Intelligence (WLI), and a multi-scale dynamic category theory, Memory
      Evolutive Systems (MES), hence WLIMES. This is presented to the modeller via a
      formal augmented reality language as a first step towards practical modelling and
      simulation of multi-level living systems. Initial work focuses on the design and
      implementation of this visual language and calculus (VLC) and its graphical user
      interface. The results will be integrated within the current methodology and
      practices of theoretical biology and (personalized) medicine to deepen and to
      enhance the holistic understanding of life.

PMID- 29042302
TI  - Attenuation of Pseudomonas aeruginosa quorum sensing, virulence and biofilm
      formation by extracts of Andrographis paniculata.
AB  - Quorum-sensing (QS) is known to play an essential role in regulation of virulence
      factors and toxins during Pseudomonas aeruginosa infection which may frequently
      cause antibiotic resistance and hostile outcomes of inflammatory injury.
      Therefore, it is an urgent need to search for a novel agent with low risk of
      resistance development that can target QS and inflammatory damage prevention as
      well. Andrographis paniculata, a herbaceous plant under the family Acanthaceae,
      native to Asian countries and also cultivated in Scandinavia and some parts of
      Europe, has a strong traditional usage with its known antibacterial, anti
      inflammatory, antipyretic, antiviral and antioxidant properties. In this study,
      three different solvent extracts (viz., chloroform, methanol and aqueous) of A.
      paniculata were examined for their anti-QS and anti-inflammatory activities.
      Study was carried out to assess the effect on some selected QS-regulatory genes
      at transcriptional level using Real Time-PCR. In addition, ability to attenuate
      MAPK pathways upon P. aeruginosa infection was performed to check its potential
      anti-inflammatory activity. Chloroform and methanol extracts showed significant
      reduction (p < 0.05) of the QS-controlled extracellular virulence factors in P.
      aeruginosa including the expression of pyocyanin, elastase, total protease,
      rhamnolipid and hemolysin without affecting bacterial viability. They also
      significantly (p < 0.05) reduced swarming motility and biofilm formation of P.
      aeruginosa. The chloroform extract, which was found to be more effective,
      decreased expression of lasI, lasR, rhlI and rhlR by 61%, 75%, 41%, and 44%,
      respectively. Moreover, chloroform extract decreased activation of p-p38 and p
      ERK1/2 expression levels in MAPK signal pathways in P. aeruginosa infected
      macrophage cells. As the present study demonstrates that A. paniculata extracts
      inhibit QS in P. aeruginosa and exhibit anti-inflammatory activities, therefore
      it represents itself as a prospective therapeutic agent against P. aeruginosa
      infection.

PMID- 29042303
TI  - Changes in serum proteins in dogs with Ehrlichia canis infection.
AB  - The aim of this study was the identification of proteins differentially
      represented in the serum proteome of seropositive dogs with (Group 1) and without
      (Group 2) clinical-pathologic signs consistent with ehrlichiosis compared to
      healthy control dogs. Serum samples were collected from 20 dogs of various breeds
      with naturally occurring ehrlichiosis (10 dogs belonged to Group 1 and 10 to
      Group 2) and 10 healthy dogs. Two-dimensional electrophoresis (2DE) of pooled
      serum for each of the group of dogs were run in triplicate. 2D image analysis
      showed 39 spots differently expressed between Group 1 and Group 2 compared with
      healthy ones. Mass spectrometry analysis allowed identification of 6 proteins:
      albumin, haptoglobin (Hp), alpha-1-antitrypsin (AAT), Retinol Binding Protein 4
      (RBP-4), alpha-1-acid glycoprotein (AGP) and vitamin D-binding protein (VDBP).
      When a confirmatory study was performed for albumin, Hp, AAT and RBP-4 by using
      different assays, significant differences (P < 0.05) between diseased and healthy
      groups were observed. It can be concluded that there are significant changes in
      the serum proteome of dogs with ehrlichiosis with modifications in proteins
      related with the acute phase response such as Hp, albumin and AGP, with vitamin A
      transport such as RBP-4, with inhibitors of serine proteases and anti
      inflammatory proteins such as AAT, and vitamin D metabolism and actin scavengers
      such as VDBP.

PMID- 29042304
TI  - Xanthine oxidase activity affects pro-oxidative and pro-inflammatory profiles in
      spleen of silver catfish experimentally infected with Aeromonas caviae.
AB  - Several pieces of evidence have linked the involvement of xanthine oxidase (XO),
      a source of uric acid and reactive oxygen species (ROS), to pro-oxidative and pro
      inflammatory effects observed during bacterial fish diseases. Thus, the aim of
      this study was to evaluate whether upregulation of splenic XO activity
      contributes to disease pathogenesis of Aeromonas caviae infection, as well as
      whether it may be considered a pathway involved in ROS and nitric oxide (NO)
      production. XO activity increased in the spleen of infected animals, as did the
      splenic levels of uric acid, ROS and metabolites of nitric oxide (NOx), compared
      to the uninfected control group. Based on this evidence, upregulation of splenic
      XO activity induces pro-oxidant and pro-inflammatory profiles in the spleen of
      fish infected by A. caviae due to excessive formation of uric acid. Moreover,
      excessive uric acid induces the release of pro-inflammatory mediators, such as
      ROS and NOx, which contribute to disease pathophysiology. In summary,
      upregulation of XO activity may be considered a pathway involved in ROS and NOx
      production.

PMID- 29042305
TI  - Influence of the fish oil in the gut microbiota of wistar rats (Rattus
      norvegicus) treated with dexamethasone and amoxicillin.
AB  - The widespread use of antibiotics and anti-inflammatory has been more and more
      prominent. In spite of the proven pharmacological potential, its collateral
      effects are still being described. The fish oil is made of acids fatty
      polyunsaturated, as the omega 3. The aim of this paper is to check if there would
      be interference of this fish oil in the gut microbiota of rats when treated with
      dexamethasone and amoxicillin, joining with the parameter lipids and glycemic.
      This study was done with 42 Wistar rats, divided into 6 groups with 7 animals
      each: naive (CTL), amoxicillin (AMOX), dexamethasone (DEX), fish oil (OLP),
      associated amoxicillin and fish oil (AMOX + OLP) association dexamethasone and
      fish oil (DEX + OLP). The results show that the fish oil influenced in the
      concentration of blood glucose in the animals, keeping stable levels even after a
      pool of glucose. Differently, the fish oil increased the levels of LDL in the
      animals. The amoxicillin changed the mass of liver and spleen, changed the levels
      of triglyceride and changed the gut microbiota. The dexamethasone influenced the
      lipids parameters and mass of the spleen as well as it slightly increased the
      amount of cholesterol LDL. It is possible to conclude that fish oil increases the
      levels of LDL in the tested model and the dose tested, but is able to maintain
      glucose levels even after a pool of the same, and can be a preventive model with
      hyperglycemia.

PMID- 29042306
TI  - Cigarette smoke induces mitochondrial metabolic reprogramming in lung cells.
AB  - Cellular transformation owing to cigarette smoking is due to chronic exposure and
      not acute. However, systematic studies to understand the molecular alterations in
      lung cells due to cigarette smoke are lacking. To understand these molecular
      alterations induced by chronic cigarette smoke exposure, we carried out tandem
      mass tag (TMT) based temporal proteomic profiling of lung cells exposed to
      cigarette smoke for upto 12months. We identified 2620 proteins in total, of which
      671 proteins were differentially expressed (1.5-fold) after 12months of exposure.
      Prolonged exposure of lung cells to smoke for 12months revealed dysregulation of
      oxidative phosphorylation and overexpression of enzymes involved in TCA cycle. In
      addition, we also observed overexpression of enzymes involved in glutamine
      metabolism, fatty acid degradation and lactate synthesis. This could possibly
      explain the availability of alternative source of carbon to TCA cycle apart from
      glycolytic pyruvate. Our data indicates that chronic exposure to cigarette smoke
      induces mitochondrial metabolic reprogramming in cells to support growth and
      survival.

PMID- 29042307
TI  - Programmable LED-based integrating sphere light source for wide-field
      fluorescence microscopy.
AB  - Wide-field fluorescence microscopy commonly uses a mercury lamp, which has
      limited spectral capabilities. We designed and built a programmable integrating
      sphere light (PISL) source which consists of nine LEDs, light-collecting optics,
      a commercially available integrating sphere and a baffle. The PISL source is
      tuneable in the range 365-490nm with a uniform spatial profile and a sufficient
      power at the objective to carry out spectral imaging. We retrofitted a standard
      fluorescence inverted microscope DM IRB (Leica) with a PISL source by mounting it
      together with a highly sensitive low- noise CMOS camera. The capabilities of the
      setup have been demonstrated by carrying out multispectral autofluorescence
      imaging of live BV2 cells.

PMID- 29042308
TI  - Abiraterone Followed by Enzalutamide Versus Enzalutamide Followed by Abiraterone
      in Chemotherapy-naive Patients With Metastatic Castration-resistant Prostate
      Cancer.
AB  - BACKGROUND: Abiraterone (AA) and enzalutamide (ENZA) are increasingly being used
      in chemotherapy-naive patients with metastatic castration-resistant prostate
      cancer owing to efficacy and favorable toxicity. However, the order in which they
      should be administered has not been determined. PATIENTS AND METHODS: We
      retrospectively reviewed the records of chemotherapy-naive patients with
      metastatic castration-resistant prostate cancer who had received sequential
      treatment with either AA followed by ENZA (AA-ENZA) or the converse (ENZA-AA).
      Prostate-specific antigen (PSA) response rates (defined as >= 50% PSA decline
      from baseline), first-line progression-free survival (PFS), second-line PFS,
      combined PFS (defined as first-line PFS plus second-line PFS), and overall
      survival are compared between the 2 sequence groups. RESULTS: A total of 97
      patients received sequential treatment with AA and ENZA; 50 patients were in the
      AA-ENZA group, and 47 patients were in the ENZA-AA group. The PSA response rate
      to first-line treatment was not significantly different between AA (48%) and ENZA
      (51%) (P = .840). However, a significant difference was observed in the PSA
      response rate to second-line treatment (AA, 6.4% vs. ENZA, 30%; P = .004). The
      median combined PFS was not significantly different between sequence groups
      (hazard ratio, 0.71; 95% confidence interval, 0.46-1.08; log-rank P = .105). The
      order of addition also had no significant effect on median overall survival
      (hazard ratio, 0.98; 95% confidence interval, 0.64-1.52; log-rank P = .834).
      CONCLUSION: With the exception of the second-line PSA response, there was no
      significant difference in clinical outcomes between the AA-ENZA and ENZA-AA
      groups. Our results might be useful reference in daily practice, especially for
      patients who do not have a suitable general condition for chemotherapy.

PMID- 29042309
TI  - The binding of botulinum neurotoxins to different peripheral neurons.
AB  - Botulinum neurotoxins are the most potent toxins known. The double receptor
      binding modality represents one of the most significant properties of botulinum
      neurotoxins and largely accounts for their incredible potency and lethality.
      Despite the high affinity and the very specific binding, botulinum neurotoxins
      are versatile and multi-tasking toxins. Indeed they are able to act both at the
      somatic and at the autonomic nervous system. In spite of the preference for
      cholinergic nerve terminals botulinum neurotoxins have been shown to inhibit to
      some extent also the noradrenergic postganglionic sympathetic nerve terminals and
      the afferent nerve terminals of the sensory neurons inhibiting the release of
      neuropeptides and glutamate, which are responsible of nociception. Therefore,
      there is increasing evidence that the therapeutic effect in both motor and
      autonomic disorders is based on a complex mode of botulinum neurotoxin action
      modulating the activity of efferent as well as afferent nerve fibres.

PMID- 29042310
TI  - Antivenom against Crotalus durissus terrificus venom: Immunochemical reactivity
      and experimental neutralizing capacity.
AB  - The venom of Crotalus durissus terrificus produces a neurotoxic and myotoxic
      syndrome that can lead to the death. Specific antivenom is the only treatment to
      neutralize the toxicity of the venom and the precocity in applying the antivenom
      is crucial for the efficiency of the treatment. We studied the variation of the
      immunochemical reactivity and neutralizing capacity of the specific antivenom on
      this venom in pre-incubation and rescue experiments, at different times. ELISA
      titers increased with longer venom-antivenom incubation times (p < 0.05)
      nevertheless incubation times had no effect on the neutralizing capacity of the
      antivenom. The antivenom dose necessary to rescue mice injected with 1.5 MMD
      (minimal mortal dose) 30 min after venom inoculation was over ten folds the dose
      of antivenom theoretically required to neutralize the same dose of venom
      according values obtained from pre-incubation experiments. Results showed that
      the in vitro immunochemical reactivity is not directly related to the
      neutralizing capacity. These observations underline the need for a rapid
      antivenom administration. Although preincubation experiments in mice are a
      powerful tool for the validation of the potency of the antivenoms in the
      productive process, it is clear that the nominal neutralization of the antivenoms
      must not be considered as a "stoichiometric" value regarding the venom to be
      neutralized in case of natural envenomation and emphasize the need of realization
      of clinical trials in order to evaluate the adequate doses of antivenom to be
      therapeutically used.

PMID- 29042311
TI  - Rational design of botulinum neurotoxin A1 mutants with improved oxidative
      stability.
AB  - Botulinum neurotoxins (BoNTs) are the most potent toxic proteins to mankind known
      but applied in low doses trigger a localized muscle paralysis that is beneficial
      for the therapy of several neurological disorders and aesthetic treatment. The
      paralytic effect is generated by the enzymatic activity of the light chain (LC)
      that cleaves specifically one of the SNARE proteins responsible for
      neurotransmitter exocytosis. The activity of the LC in a BoNT-containing
      therapeutic can be compromised by denaturing agents present during manufacturing
      and/or in the cell. Stabilization of the LC by reducing vulnerability towards
      denaturants would thus be advantageous for the development of BoNT-based
      therapeutics. In this work, we focused on increasing the stability of LC of
      BoNT/A1 (LC/A1) towards oxidative stress. We tackled this task by rational design
      of mutations at cysteine and methionine LC/A1 sites. Designed mutants showed
      improved oxidative stability in vitro and equipotency to wildtype toxin in vivo.
      Our results suggest that suitable modification of the catalytic domain can lead
      to more stable BoNTs without impairing their therapeutic efficacy.

PMID- 29042312
TI  - Extracellular expression of the HT1 neurotoxin from the Australian paralysis tick
      in two Saccharomyces cerevisiae strains.
AB  - Surface display libraries (SDL) have predominantly been utilized for the
      screening of peptides, and single-chain variable IgG fragments, however, the use
      of SDL for the expression and purification of proteins is gaining interest.
      Prokaryote SDL express proteins within the periplasm, limiting the application of
      common screening techniques, such as ELISA and FACS, to assess the viability of
      recombinant toxin before purification. A previous attempt to express a functional
      holocyclotoxin-1 (HT1) from the Australian paralysis tick (Ixodes holocyclus)
      using a prokaryotic system was unsuccessful. In this study, the coding sequence
      (CDS) of HT1 was cloned into the pYD1 plasmid and transformed by electroporation
      into IMTV014 and EBY100 yeast cell lines. Post induction, recombinant HT1 was
      identified on the cell surface of IMTV014/ht1 and EBY100/ht1 transformants by
      FACS, Western blot, and ELISA utilizing dog anti-paralysis tick IgG. The
      recombinant HT1 was purified, and functionality confirmed by an in vitro
      synaptosome-binding assay. This research reports for the first time the
      extracellular expression and display of a functional HT1 on the surface of the S.
      cerevisiae. It also provides evidence that yeast display libraries provide a
      viable technology to produce recombinant toxins, and their screening using high
      throughput methodologies such as FACS.

PMID- 29042314
TI  - Differential distribution and function of GABABRs in somato-dendritic and axonal
      compartments of principal cells and interneurons in cortical circuits.
AB  - GABABRs are highly expressed in cortical circuits, controlling neuronal
      excitability and synaptic transmission in both principal cells and inhibitory
      interneurons. Light and electron microscopic studies confirmed the wide
      distribution of receptors and revealed cell type-specific quantitative
      differences in their cellular and subcellular distributions. At the subcellular
      level, GABABRs are abundant at the peri- and extrasynaptic membrane of somato
      dendritic compartments and to lower levels in the axon terminals of both cortical
      excitatory principal cells and inhibitory interneurons. Differences in the
      surface densities are particularly prominent between neurochemically-defined
      interneuron types. Whole-cell recordings further demonstrated that GABABRs
      differentially mediate post- and presynaptic inhibition in principal cells and
      various GABAergic interneurons by preferentially modulating postsynaptic G
      protein-coupled inwardly rectifying K+ (Kir3) channels and presynaptic high
      voltage-activated Ca2+ (Cav) channels. These data convergently indicate that
      GABABRs not only control the overall level of neuronal excitability and activity,
      but can also fine tune the activation and interactions of excitatory and
      inhibitory neurons in cortical circuits. This article is part of the "Special
      Issue Dedicated to Norman G. Bowery".

PMID- 29042313
TI  - The hypothetical protein P47 of Clostridium botulinum E1 strain Beluga has a
      structural topology similar to bactericidal/permeability-increasing protein.
AB  - Botulinum neurotoxins (BoNTs) are causative agents of the life-threatening
      disease botulism. They are naturally produced by species of the bacteria
      Clostridium botulinum as stable and non-covalent complexes, in which the BoNT
      molecule is assembled with several auxiliary non-toxic proteins. Some BoNT
      serotypes, represented by the well-studied BoNT serotype A (BoNT/A), are produced
      by Clostridium strains that carry the ha gene cluster, which encodes four
      neurotoxin-associated proteins (NTNHA, HA17, HA33, and HA70) that play an
      important role to deliver and protect BoNTs in the gastrointestinal tract during
      oral intoxication. In contrast, BoNT/E- and BoNT/F-producing strains carry a
      distinct gene cluster that encodes five proteins (NTNHA, P47, OrfX1, OrfX2, and
      OrfX3, termed the orfX cluster). The structures and functions of these proteins
      remain largely unknown. Here, we report the crystal structure of P47 resolved at
      2.8 A resolution. Surprisingly, P47 displays a structural topology that is
      similar to bactericidal/permeability-increasing (BPI) like proteins, which were
      previously identified only in eukaryotes. The similarity of a hydrophobic cleft
      of P47 with the phospholipid-binding groove of BPI suggests that P47 might be
      involved in lipid association to exert its function. Consistently, P47 associates
      and induces aggregation of asolectin-containing liposomes in a protein- and lipid
      concentration dependent manner. These findings laid the foundation for future
      structural and functional studies of the potential roles of P47 and OrfX proteins
      in facilitating oral intoxication of BoNTs.

PMID- 29042315
TI  - IL-1beta reduces GluA1 phosphorylation and its surface expression during memory
      reconsolidation and alpha-melanocyte-stimulating hormone can modulate these
      effects.
AB  - Pro-inflammatory cytokines can affect cognitive processes such as learning and
      memory. Particularly, interleukin-1beta (IL-1beta) influences hippocampus
      dependent memories. We previously reported that administration of IL-1beta in
      dorsal hippocampus impaired contextual fear memory reconsolidation. This effect
      was reversed by the melanocortin alpha-melanocyte-stimulating hormone (alpha
      MSH). Our results also demonstrated that IL-1beta produced a significant decrease
      in glutamate release from dorsal hippocampus synaptosomes after reactivation of
      the fear memory. Therefore, we investigated whether IL-1beta administration can
      affect GluA1 AMPA subunit phosphorylation, surface expression, and total
      expression during reconsolidation of a contextual fear memory. Also, we studied
      the modulatory effect of alpha-MSH. We found that IL-1beta reduced
      phosphorylation of this subunit at Serine 831 and Serine 845 60 min after
      contextual fear memory reactivation. The intrahippocampal administration of IL
      1beta after memory reactivation also induced a decrease in surface expression and
      total expression of GluA1. alpha-MSH prevented the effect of IL-1beta on GluA1
      phosphorylation in Serine 845, but not in Serine 831. Moreover, treatment with
      alpha-MSH also prevented the effect of the cytokine on GluA1 surface and total
      expression after memory reactivation. Our results demonstrated that IL-1beta
      regulates phosphorylation of GluA1 and may thus play an important role in
      modulation of AMPAR function and synaptic plasticity in the brain. These findings
      further illustrate the importance of IL-1beta in cognition processes dependent on
      the hippocampus, and also reinforced the fact that alpha-MSH can reverse IL-1beta
      effects on memory reconsolidation.

PMID- 29042316
TI  - Repeated exposure to 3,4-methylenedioxypyrovalerone and cocaine produces
      locomotor sensitization with minimal effects on brain monoamines.
AB  - Synthetic cathinones, known as "bath salts" on the illicit drug market, pose a
      significant public health concern. 3,4-Methylenedioxypyrovalerone (MDPV), one of
      several popular constituents of illicit bath salts, produces similar
      pharmacological actions to cocaine, albeit with greater potency and efficacy. The
      present study sought to characterize behavioral and neurochemical effects of
      repeated exposure to MDPV alone and in combination with cocaine. Male Sprague
      Dawley rats were randomly assigned to one the following four treatments,
      administered once daily for seven days: 1 mg/kg MDPV, 5 mg/kg cocaine, 1 mg/kg
      MDPV +5 mg/kg cocaine, or saline. Locomotor activity was assessed for 1 h
      immediately before and 1 h immediately after injections on days 1 and 6. Brains
      were harvested 20 min after the final injection on day 7 and brain tissue punches
      were obtained to determine monoamine content within the anterior striatum, medial
      prefrontal cortex, and nucleus accumbens using High-Performance Liquid
      Chromatography (HPLC). Drug-induced increases in horizontal activity were
      significantly greater on treatment day 6 compared to treatment day 1 in all three
      drug treatment groups in comparison to the saline control group. MDPV produced
      significantly higher increases in activity compared to either saline or cocaine,
      although concurrent treatment with MDPV and cocaine produced sub-additive
      effects. Neurochemical analyses provided no evidence of alterations in total
      monoamine content following repeated administration of MDPV, cocaine, or the MDPV
      + COC mixture. Further investigations targeting possible changes in DA receptor
      sensitivity following repeated exposure to MDPV may help elucidate the
      mechanistic changes responsible for MDPV-induced behavioral sensitization. This
      article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'

PMID- 29042317
TI  - Fentanyl, fentanyl analogs and novel synthetic opioids: A comprehensive review.
AB  - Deaths from opioid use are increasing in the US, with a growing proportion due to
      synthetic opioids. Until 2013, sporadic outbreaks of fentanyl and fentanyl
      analogs contaminating the heroin supply caused some deaths in heroin users. Since
      then, fentanyl has caused deaths in every state and fentanyl and its analogs have
      completely infiltrated the North American heroin supply. In 2014, the first
      illicit pills containing fentanyl, fentanyl analogs, and other novel synthetic
      opioids such as U-47700 were detected. These pills, which look like known opioids
      or benzodiazepines, have introduced synthetic opioids to more unsuspecting
      customers. As soon as these drugs are regulated by various countries, new
      compounds quickly appear on the market, making detection difficult and the number
      of cases likely underreported. Standard targeted analytical techniques such as GC
      MS (gas chromatography mass spectrometry) and LC-MS/MS (liquid chromatography
      tandem mass spectrometry) can detect these drugs, but novel compound
      identification is aided by nontargeted testing with LC-HRMS (liquid
      chromatography high resolution mass spectrometry). Fentanyl, fentanyl analogs and
      other novel synthetic opioids are all full agonists of varying potencies at the
      MU-opioid receptor, leading to typical clinical effects of miosis and respiratory
      and central nervous system depression. Due to their high affinity for MU-opioid
      receptors, larger doses of naloxone are required to reverse the effects than are
      commonly used. Synthetic opioids are an increasingly major public health threat
      requiring vigilance from multiple fields including law enforcement, government
      agencies, clinical chemists, pharmacists, and physicians, to name a few, in order
      to stem its tide. This article is part of the Special Issue entitled 'Designer
      Drugs and Legal Highs.'

PMID- 29042319
TI  - Photochemical delivery of bleomycin induces T-cell activation of importance for
      curative effect and systemic anti-tumor immunity.
AB  - Photochemical internalization (PCI) is a technology to enhance intracellular drug
      delivery by light-induced translocation of endocytosed therapeutics into the
      cytosol. The aim of this study was to explore the efficacy of PCI-based delivery
      of bleomycin and the impact on systemic anti-tumor immunity. Mouse colon
      carcinoma cells (CT26.CL25), stably expressing the bacterial beta-galactosidase,
      were inoculated into the legs of athymic or immuno-competent BALB/c mice strains.
      The mice were injected with the photosensitizer AlPcS2a and bleomycin (BLM) prior
      to tumor light exposure from a 670nm diode laser. Photochemical activation of BLM
      was found to induce synergistic inhibition of tumor growth as compared to the sum
      of the individual treatments. However, a curative effect was not observed in the
      athymic mice exposed to 30J/cm2 of light while >90% of the thymic mice were cured
      after exposure to only 15J/cm2 light. Cured thymic mice, re-challenged with
      CT26.CL25 tumor cells on the contralateral leg, rejected 57-100% of the tumor
      cells inoculated immediately and up to 2months after the photochemical treatment.
      T-cells from the spleen of PCI-treated mice were found to inhibit the growth of
      CT26.CL25 cells in naive thymic mice with a 60% rejection rate. The results show
      that treatment of CT26.CL25 tumors in thymic mice by PCI of BLM induces a
      systemic anti-tumor immunity.

PMID- 29042321
TI  - Multimodal imaging approach to examine biodistribution kinetics of Cabotegravir
      (GSK1265744) long acting parenteral formulation in rat.
AB  - Long-Acting Parenterals (LAPs) have been used in the clinic to provide sustained
      therapeutic drug levels at a target site, and thereby reducing the frequency of
      dosing required. In an effort to understand the factors associated with long
      acting cabotegravir (GSK1265744 LAP) pharmacokinetic variability, the current
      study was designed to investigate the temporal relationship between intramuscular
      (IM) or subcutaneous (SC) drug depot morphology and distribution kinetics with
      plasma pharmacokinetics. Therefore, a multi-modal molecular imaging (MRI & MALDI
      IMS) approach was employed to examine the temporal GSK1265744 LAP biodistribution
      in rat following either IM or SC administration. Serial MRI was performed
      immediately post drug administration, and then at day 1 (24h post), 2, 3, 4, 7,
      and 14. In a separate cohort of rats, an MRI contrast agent, Feraheme(r) (USPIO),
      was administered 2days post IM drug injection in order to investigate the
      potential involvement of macrophages trafficking to the GSK1265744 LAP and
      Vehicle depot sites. The GSK1265744 LAP depot volume increased rapidly by day 2
      in the IM injected rats (~3-7 fold) compared with a ~1 fold increase in the SC
      injected rats. In addition, the USPIO contrast agent labeled macrophages were
      shown to be present in the depot region of the GSK1265744 LAP injected
      gastrocnemius while the Vehicle injected gastrocnemius appeared to show reduced
      uptake. Matrix-assisted laser desorption ionization (MALDI) imaging mass
      spectrometry (IMS) of muscle and abdominal tissue sections identified the drug
      content primarily within the depot. Co-registration of the GSK1265744 ion images
      with immunohistochemical images established that the drug was taken up by
      macrophages associated with the depot. Linear regression analysis demonstrated
      that the drug depot characteristics including volume, surface area, and perimeter
      assessed by MRI at day 2 correlated with early time point plasma drug
      concentrations. In summary, a multimodal molecular imaging approach was used to
      identify the drug depot location and volumetric/physiologic changes in both IM
      and SC locations following GSK1265744 LAP administration. The IM depot volume
      increased rapidly to a maximum volume at 2days post-GSK1265744 LAP
      administration, while the Vehicle depot did not suggesting that the active drug
      substance and/or related particle was a key driver for drug depot evolution. The
      depot expansion was associated with an increase in macrophage infiltration and
      edema in and around the depot region and was correlated to plasma drug
      concentration at early time points (0-4days). Consequently, molecular imaging
      approaches may be used in patients to help understand the biodistribution of
      GSK1265744 LAP and its associated pharmacokinetics.

PMID- 29042318
TI  - Mechanisms of MU-opioid receptor inhibition of NMDA receptor-induced substance P
      release in the rat spinal cord.
AB  - The interaction between NMDA receptors and MU-opioid receptors in primary
      afferent terminals was studied by using NMDA to induce substance P release,
      measured as neurokinin 1 receptor internalization. In rat spinal cord slices, the
      MU-opioid receptor agonists morphine, DAMGO and endomorphin-2 inhibited NMDA
      induced substance P release, whereas the antagonist CTAP right-shifted the
      concentration response of DAMGO. In vivo, substance P release induced by
      intrathecal NMDA after priming with BDNF was inhibited by DAMGO. omega-Conotoxins
      MVIIC and GVIA inhibited about half of the NMDA-induced substance P release,
      showing that it was partially mediated by the opening of voltage-gated calcium
      (Cav) channels. In contrast, DAMGO or omega-conotoxins did not inhibit capsaicin
      induced substance P release. In cultured DRG neurons, DAMGO but not omega
      conotoxin inhibited NMDA-induced increases in intracellular calcium, indicating
      that MU-opioid receptors can inhibit NMDA receptor function by mechanisms other
      than inactivation of Cav channels. Moreover, DAMGO decreased the omega-conotoxin
      insensitive component of the substance P release. Potent inhibition by ifenprodil
      showed that these NMDA receptors have the NR2B subunit. Activators of adenylyl
      cyclase and protein kinase A (PKA) induced substance P release and this was
      decreased by the NMDA receptor blocker MK-801 and by DAMGO. Conversely,
      inhibitors of adenylyl cyclase and PKA, but not of protein kinase C, decreased
      NMDA-induced substance P release. Hence, these NMDA receptors are positively
      modulated by the adenylyl cyclase-PKA pathway, which is inhibited by MU-opioid
      receptors. In conclusion, MU-opioid receptors inhibit NMDA receptor-induced
      substance P release through Cav channel inactivation and adenylyl cyclase
      inhibition.

PMID- 29042322
TI  - Activation of Parvalbumin Neurons in the Rostro-Dorsal Sector of the Thalamic
      Reticular Nucleus Promotes Sensitivity to Pain in Mice.
AB  - The calcium-binding protein, parvalbumin (PV), is highly expressed in thalamic
      reticular nucleus (TRN) GABAergic neurons, which receive input from the cerebral
      cortex and thalamus and send inhibitory output to the thalamic relay nucleus.
      Previous studies suggest that the TRN is involved in pain regulation as an
      important relay nucleus of the ascending pain pathway. However, little is known
      about its functional role in pain regulation and interconnectivity. In our study,
      the role of rostro-dorsal sector of TRN (TRNrd) PV-positive neurons in pain
      regulation was studied using chemogenetics based on designer receptors
      exclusively activated by designer drugs (DREADD). Then, projections from the
      TRNrd PV-positive neurons were explored using PV-Cre transgenic mice, conditional
      anterograde axonal tract tracing, and optogenetics, combined with
      immunohistochemistry and electrophysiology. The results showed that activation of
      PV-positive neurons in the TRNrd decreased the mechanical threshold and thermal
      latency of behaving mice during the light period when neuronal activity was low.
      Furthermore, the anterodorsal and paratenial thalamic nucleus received
      innervation from PV-positive neurons in the TRNrd. They were specifically
      inhibited by GABA, which is released from local axonal endings of PV neurons.
      These findings indicate that activation of PV neurons in the TRNrd increases pain
      sensitivity in PV-Cre transgenic mice.

PMID- 29042323
TI  - Diversity and abundance of Beauveria bassiana in soils, stink bugs and plant
      tissues of common bean from organic and conventional fields.
AB  - The aim of this study was to evaluate the natural occurrence of Beauveria spp. in
      soil, from infections in the stink bug Piezodorus guildinii, an important pest of
      common bean (Phaseolus vulgaris) and as endophytes in bean plant tissue. Twelve
      conventional and 12 organic common bean fields in the Villa Clara province, Cuba
      were sampled from September 2014 to April 2015. One hundred and fifty Beauveria
      isolates were obtained from soil samples, bean plant parts and stink bugs. The
      overall frequency of occurrence of Beauveria isolates in conventional fields
      (8.4%) was significantly lower than that in organic fields (23.6%). Beauveria
      were also obtained significantly more frequently from bean roots in organic
      fields (15.0%) compared to bean roots in conventional fields (3.3%). DNA
      sequencing of the intergenic Bloc region was performed for Beauveria species
      identification. All isolates where characterized as Beauveria bassiana (Balsamo
      Crivelli) Vuillemin, and clustered with isolates of neotropical origin previously
      described as AFNEO_1. The Cuban B. bassiana isolates formed five clusters in the
      phylogeny. Isolates of two clusters originated from all four locations, organic
      and conventional fields, as well as soil, plants and stink bugs. Organic fields
      contained isolates of all five clusters while conventional fields only harbored
      isolates of the two most frequent ones. Mating type PCR assays revealed that
      mating type distribution was skewed, with MAT1/MAT2 proportion of 146/4,
      indicating limited potential for recombination. The present study is the first to
      report of B. bassiana as a naturally occurring endophyte in common bean. Further,
      it shows that B. bassiana occurs naturally in diverse environments of common bean
      fields, and constitutes a potential reservoir of natural enemies against pest
      insects particularly in organic fields.

PMID- 29042324
TI  - Characterization of hemocytes from different body fluids of the eastern oyster
      Crassostrea virginica.
AB  - Bivalve hemocytes are involved in a variety of physiological and immunological
      functions. Circulating hemocytes in the hemolymph represent the main component of
      the internal self-defense system while hemocytes present in the extrapallial
      space (between the mantle and the shell) are actively involved in
      biomineralization and shell formation. This study focused on the characterization
      of hemocytes from different body fluids of the eastern oyster Crassostrea
      virginica. Hemocytes present in the hemolymph were compared to those contained in
      the extrapallial fluid. Hemocytes associated with the mucus layer covering
      pallial organs (mantle, gills, body wall) were also investigated because of their
      potential role as sentinel cells. Hemocytes were characterized using flow
      cytometry in conjunction with fluorescent epitope markers (clusters of
      differentiation, lectins) as well as functional assays (i.e. phagocytosis and
      reactive oxygen species -ROS). Compared with the hemolymph, there was a
      significantly greater percentage of granulocytes and agranulocytes among
      extrapallial and pallial hemocytes, respectively. Accounting for the different
      percentages of hemocyte sub-populations, significant differences in surface
      carbohydrate and clusters of differentiation signatures were also revealed
      between the different fluids. Most informative epitope markers included
      concanavalin A, peanut agglutinin, soybean agglutinin, CD11b and CD14. Functional
      assays revealed significant differences in phagocytic activity and ROS production
      between hemocytes from the extrapallial fluid and hemolymph; however, less robust
      differences were observed between hemolymph cells and hemocytes associated with
      the pallial mucus. Findings from this study suggest that there are markedly
      different hemocyte populations in the three body fluids. The role of peripheral
      cells, particularly those associated with the pallial mucus, requires further
      investigations.

PMID- 29042320
TI  - Bone-targeting nanoparticle to co-deliver decitabine and arsenic trioxide for
      effective therapy of myelodysplastic syndrome with low systemic toxicity.
AB  - Myelodysplastic syndromes (MDS) are a diverse group of bone marrow disorders and
      clonal hematopoietic stem cell disorders characterized by abnormal blood cells,
      or reduced peripheral blood cell count. Recent clinical studies on combination
      therapy of decitabine (DAC) and arsenic trioxide (ATO) have demonstrated synergy
      on MDS treatment, but the treatment can cause significant side effects to
      patients. In addition, both drugs have to be administered on a daily basis due to
      their short half-lives. In addressing key issues of reducing toxic side effects
      and improving pharmacokinetic profiles of the therapeutic agents, we have
      developed a new formulation by co-packaging DAC and ATO into alendronate
      conjugated bone-targeting nanoparticles (BTNPs). Our pharmacokinetic studies
      revealed that intravenously administered BTNPs increased circulation time up to
      3days. Biodistribution analysis showed that the BTNP facilitated DAC and ATO
      accumulation in the bone, which is 6.7 and 7.9 times more than untargeted NP.
      Finally, MDS mouse model treated with BTNPs showed better restoration of complete
      blood count to normal level, and significantly longer median survival as compared
      to free drugs or untargeted NPs treatment. Our results support bone-targeted co
      delivery of DAC and ATO for effective treatment of MDS.

PMID- 29042325
TI  - Characterize a typically Dscam with alternative splicing in mud crab Scylla
      paramamosain.
AB  - As a member of the immunoglobulin superfamily, Down syndrome cell adhesion
      molecule (Dscam) could function in the innate immunity of invertebrates.
      Recently, it is shown that arthropod Dscams play similar functions as antibodies
      in the adaptive immune system. Dscam could produce thousands of isoforms by
      alternative splicing and specifically bind to various pathogens. In the present
      study, we cloned the first Dscam from mud crab Scylla paramamosain (SpDscam),
      with full-length cDNA 7363 bp containing an open reading frame (ORF) of 6069bp
      and encoding 2022 amino acids, which had typical domain architecture as other
      arthropods, i.e., 10 immunoglobulin domains (Ig), 6 fibronectin type 3 domains
      (FN III), transmembrane and cytoplasmic tail. Quantitative real-time PCR revealed
      that SpDscam was highly expressed in brain, skin, muscle, intestine and
      hepatopancreas, but weakly expressed in hemolymph, heart and gill. SpDscam had
      three alternative splicing regions, located at the N-terminal of Ig2 and Ig3 as
      well as on the whole Ig7. In these regions, 32, 41 and 14 exons were detected,
      together with the two exon types of transmembrane domain, indicating SpDscam
      could potentially encode at least 36,736 unique isoforms. SpDscam induced by
      Vibrio parahaemolyticus challenge had strong binding ability to V.
      parahaemolyticus. Further, SpDscam induced by V. parahaemolyticus possessed a
      clearance of V. parahaemolyticus in S. paramamosain. Collectively, the results
      indicated SpDscam was a hypervariable pattern-recognition receptor (PRR) by
      alternative splicing in innate immunity system of mud crab S. paramamosain.

PMID- 29042327
TI  - Research, regulatory, and clinical decision-making: the importance of scientific
      integrity.

PMID- 29042328
TI  - Ruptured Persistent Trigeminal Artery Causing Direct Cavernous Sinus Fistula
      Treated with Pipeline Embolization and Minimal Coiling.
AB  - BACKGROUND: Rupture of a persistent trigeminal artery associated with development
      of a cavernous sinus fistula in a traumatic setting is rare. These arteries are
      typically treated with coil embolization of the cavernous sinus. CASE
      DESCRIPTION: We present the case of a 42-year-old woman who developed a direct
      cavernous carotid fistula after a motor vehicle accident. Angiographic imaging
      revealed a rupture point of a persistent trigeminal artery as it connected with
      the cavernous segment of the internal carotid artery, causing a cavernous sinus
      fistula. Coiling of the cavernous sinus was abandoned after placement of 1 coil
      because of coil herniation into the internal carotid artery. A Pipeline
      embolization device was placed to oppose the coil against the intima and keep the
      lumen open. The combination of coil embolization and flow diversion acutely
      decreased the fistulous flow. Surprisingly, an angiographic follow-up at 6 months
      showed complete fistula occlusion despite placement of only 1 coil into the
      cavernous sinus. CONCLUSIONS: We report a rare case where undercoiling of the
      cavernous sinus occluded a cavernous sinus fistula because of the adjunct use of
      a Pipeline embolization device in the presence of a traumatic rupture of a
      persistent trigeminal artery.

PMID- 29042329
TI  - Rare Giant Prevertebral Thoracic Myelomeningocele.
AB  - Here we report a 72-year-old man who presented with complaint of sudden-onset
      weakness and impaired sensation in the left lower extremity. Radiographic
      evaluation revealed a congenital malformation with multiple formation defects
      including a giant thoracic prevertebral myelomeningocele. Following microsurgical
      detethering of the spinal cord, the patient recovered ambulation with assist.
      While thoracic myelomeningoceles are themselves rare, in this case the patient
      presented at a late age and responded well to conservative management.

PMID- 29042330
TI  - First Depiction of Flow Voids to Differentiate Pituicytomas from Giant Adenomas.
AB  - Pituicytomas are rare low-grade glial lesions of neurohypophysis or
      adenohypophysis. They are often misdiagnosed as adenomas due to their similar
      morphology. Previous reports have underlined their nonspecific aspect. In our
      experience, presence of flow voids on magnetic resonance, which usually indicate
      hypervascularized tumors with strong arterial supply, may be a useful sign to
      identify pituicytomas. Unlike adenomas, pituicytomas are highly vascularized
      tumors. Second, we emphasize the strong enhancement of these tumors when compared
      with normal hypophysis, which may be another sign of their hypervascularization.
      Indeed, adenomas, on the opposite side, present less enhancement than normal
      hypophysis. This observation is corroborated by previous histologic studies that
      showed adenomas present less vascular density than normal pituitary glands.
      However, in large tumors, the normal hypophysis can sometimes not be
      individualized and thus the enhancement gradient between the tumor and normal
      tissue cannot be properly assessed. Due to their rarity, no previous reports had
      ever emphasized the specific signs that could allow us to differentiate
      pituicytomas from adenomas; however, it seems crucial due to the potential
      hemorrhagic complications of pituicytoma surgery.

PMID- 29042326
TI  - The molecular and cellular basis of rhodopsin retinitis pigmentosa reveals
      potential strategies for therapy.
AB  - Inherited mutations in the rod visual pigment, rhodopsin, cause the degenerative
      blinding condition, retinitis pigmentosa (RP). Over 150 different mutations in
      rhodopsin have been identified and, collectively, they are the most common cause
      of autosomal dominant RP (adRP). Mutations in rhodopsin are also associated with
      dominant congenital stationary night blindness (adCSNB) and, less frequently,
      recessive RP (arRP). Recessive RP is usually associated with loss of rhodopsin
      function, whereas the dominant conditions are a consequence of gain of function
      and/or dominant negative activity. The in-depth characterisation of many
      rhodopsin mutations has revealed that there are distinct consequences on the
      protein structure and function associated with different mutations. Here we
      categorise rhodopsin mutations into seven discrete classes; with defects ranging
      from misfolding and disruption of proteostasis, through mislocalisation and
      disrupted intracellular traffic to instability and altered function. Rhodopsin
      adRP offers a unique paradigm to understand how disturbances in photoreceptor
      homeostasis can lead to neuronal cell death. Furthermore, a wide range of
      therapies have been tested in rhodopsin RP, from gene therapy and gene editing to
      pharmacological interventions. The understanding of the disease mechanisms
      associated with rhodopsin RP and the development of targeted therapies offer the
      potential of treatment for this currently untreatable neurodegeneration.

PMID- 29042331
TI  - The First Experience of Triple Nerve Transfer in Proximal Radial Nerve Palsy.
AB  - BACKGROUND: Injury to distal portion of posterior cord of brachial plexus leads
      to palsy of radial and axillary nerves. Symptoms are usually motor deficits of
      the deltoid muscle; triceps brachii muscle; and extensor muscles of the wrist,
      thumb, and fingers. Tendon transfers, nerve grafts, and nerve transfers are
      options for surgical treatment of proximal radial nerve palsy to restore some
      motor functions. Tendon transfer is painful, requires a long immobilization, and
      decreases donor muscle strength; nevertheless, nerve transfer produces promising
      outcomes. We present a patient with proximal radial nerve palsy following a blunt
      injury undergoing triple nerve transfer. CASE DESCRIPTION: The patient was
      involved in a motorcycle accident with complete palsy of the radial and axillary
      nerves. After 6 months, on admission, he showed spontaneous recovery of axillary
      nerve palsy, but radial nerve palsy remained. We performed triple nerve transfer,
      fascicle of ulnar nerve to long head of the triceps branch of radial nerve,
      flexor digitorum superficialis branch of median nerve to extensor carpi radialis
      brevis branch of radial nerve, and flexor carpi radialis branch of median nerve
      to posterior interosseous nerve, for restoration of elbow, wrist, and finger
      extensions, respectively. CONCLUSIONS: Our experience confirmed functional elbow,
      wrist, and finger extensions in the patient. Triple nerve transfer restores
      functions of the upper limb in patients with debilitating radial nerve palsy
      after blunt injuries.

PMID- 29042332
TI  - The Relevance of Simpson Grade Resections in Modern Neurosurgical Treatment of
      World Health Organization Grade I, II, and III Meningiomas.
AB  - OBJECTIVE: The Simpson grading system has played an important role in surgical
      resections of meningiomas. The aim of this study was to determine if this grading
      system predicts meningioma recurrence in a modern cohort of patients with tumors
      of all World Health Organization grades. METHODS: Adult patients who underwent
      primary, nonbiopsy resection of a meningioma at a tertiary care institution
      between 2007 and 2015 were retrospectively reviewed. Stepwise multivariate
      proportional hazard analyses were used to identify associations with recurrence
      after resection. Log-rank analyses were used to compare Kaplan-Meier plots for
      time to recurrence between each Simpson grade. RESULTS: Of 572 patients who met
      inclusion criteria, 72 (12.6%) presented with recurrence. Factors associated with
      recurrence after gross total resection (Simpson grades I-III) were non-World
      Health Organization grade I (hazard ratio [HR] [95% confidence interval (CI)]
      6.215 [2.864-12.419], P < 0.0001) and preoperative neurologic deficits (HR [95%
      CI] 2.862 [1.512-5.499], P = 0.001). Factors associated with recurrence after
      subtotal resections (Simpson IV) were African American race (HR [95% CI] 2.776
      [1.232-5.890], P = 0.02) and parafalcine location (HR [95% CI] 3.956 [1.624
      8.775], P = 0.004). Simpson grade was not an independent risk factor for
      recurrence. CONCLUSIONS: Identification and consideration of factors associated
      with recurrence after gross total or subtotal resections may help guide treatment
      strategies for patients with meningiomas.

PMID- 29042333
TI  - Postoperative Intravenous Acetaminophen for Craniotomy Patients: A Randomized
      Controlled Trial.
AB  - OBJECTIVE: To determine whether opioids during the first 24 postoperative hours
      were significantly altered when receiving intravenous (IV) acetaminophen during
      that time compared with those receiving placebo (normal saline). METHODS: One
      hundred forty patients undergoing any type of craniotomy were randomly assigned
      to receive either 1 g of IV acetaminophen or placebo upon surgical closure, and
      every 6 hours thereafter, up to 18 hours postoperatively. Analgesic requirements
      for the first 24 postoperative hours were recorded. Time to rescue medications in
      the postanesthesia care unit (PACU)/intensive care unit (ICU), amount of rescue
      medication, ICU and hospital lengths of stay, number of successful neurological
      examinations, sedation, delirium, satisfaction, and visual analog scale pain
      scores were also recorded. RESULTS: Compared with the placebo group, more
      patients in the IV acetaminophen group (10/66 [15.2%] vs. 4/65 [6.2%] in the
      placebo group) did not require opioids within the first 24 postoperative hours,
      but this did not reach significance (odds ratio, -9.0%, 95% confidence interval 
      20.5% to 1.8%; P = 0.166). Both groups had similar times to rescue medications,
      amounts of rescue medications, ICU and hospital lengths of stay, numbers of
      successful neurological examinations, sedation, delirium, satisfaction scores,
      visual analog scale pain scores, and temperatures within the first 24
      postoperative hours. CONCLUSIONS: The opioid requirements within the first 24
      postoperative hours were similar in the placebo and acetaminophen groups. This
      study is informative for the design and planning of future studies investigating
      the management of postoperative pain in patients undergoing craniotomies.

PMID- 29042334
TI  - Primary Diffuse Large B-Cell Lymphoma in a Patient with Rubinstein-Taybi
      Syndrome: Case Report and Review of the Literature.
AB  - BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a rare, congenital syndrome that
      is known to be associated with neoplasms of various organ systems. Evaluation and
      treatment of such patients is challenging, given the cognitive delay and
      heterogeneity of pathologic presentations that define this syndrome. CASE
      DESCRIPTION: Presented here is a case of a patient with RSTS, diagnosed at birth,
      who presented with subtle symptoms of lethargy and a change in behavior. He was
      found to have a large (7.0-cm * 4.7-cm), right-sided brain mass that was
      eventually diagnosed as a primary central nervous system lymphoma. CONCLUSIONS:
      To the best of our knowledge, this is the first reported case of a primary
      central nervous system lymphoma presenting in a patient with RSTS. This was
      confirmed through microscopic and histologic studies. The large size attained by
      this mass in our patient highlights the increased scrutiny and surveillance
      needed to provide the best care for these patients. A multidisciplinary team
      approach is ideal as successful treatment of our patient using surgical
      debulking, appropriate chemotherapy, and close postoperative follow-up has
      resulted in an excellent clinical outcome.

PMID- 29042335
TI  - Neurosurgical Resident Error: A Survey of U.S. Neurosurgery Residency Training
      Program Directors' Perceptions.
AB  - BACKGROUND: Efforts to address resident errors and to enhance patient safety have
      included systemic reforms, such as the Accreditation Council for Graduate Medical
      Education's (ACGME's) mandated duty-hour restrictions, and specialty-specific
      initiatives such as the neurosurgery Milestone Project. However, there is
      currently little data describing the basis for these errors or outlining trends
      in neurosurgical resident error. METHODS: An online questionnaire was distributed
      to program directors of 108 U.S. neurosurgery residency training programs to
      assess the frequency, most common forms and causes of resident error, the
      resulting patient outcomes, and the steps taken by residency programs to address
      these errors. RESULTS: Thirty-one (28.7%) responses were received.
      Procedural/surgical error was the most commonly observed type of error. Transient
      injury and no injury to the patient were perceived to be the 2 most frequent
      outcomes. Inexperience or resident mistake despite adequate training were cited
      as the most common causes of error. Twenty-three (74.2%) respondents stated that
      a lower post graduate year level correlated with an increased incidence of
      errors. There was a trend toward an association between an increased number of
      residents within a program and the number of errors attributable to a lack of
      supervision (r = 0.36; P = 0.06). Most (93.5%) program directors do not believe
      that mandated duty-hour restrictions reduce error frequency. CONCLUSIONS: Program
      directors believe that procedural error is the most commonly observed form of
      error, with post graduate year level believed to be an important predictor of
      error frequency. The perceived utility of systemic reforms that aim to reduce the
      incidence of resident error remains unclear.

PMID- 29042336
TI  - Physicochemical properties of inclusion complexes of highly soluble beta
      cyclodextrins with highly hydrophobic testosterone propionate.
AB  - Hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and sulfobutyl ether-beta
      cyclodextrin (SBE-beta-CyD) were used to generate hydrophilic complexes of the
      poorly water-soluble drug testosterone propionate (TP). The inclusion complexes
      were obtained by freeze-drying, and then analyzed at both liquid and solid
      states. Phase solubility studies, performed according to the type-AL solubility
      diagrams of TP in presence of both CyDs, suggested the formation of water-soluble
      complexes at 1:1 molar ratio. These results were confirmed by continuous
      variation method (Job's plot). Both CyDs increased water-solubility of TP 100
      fold as compared to the native drug. The host-guest arrangement of CyD complexes
      in a water solution was further investigated by one- and two-dimensional NMR
      spectroscopy, highlighting the insertion of the tetracyclic ring of TP into the
      CyD cavity, and the interaction of the pending ester chain of drug with the
      primary hydroxyl groups of CyDs at the narrow end of the toroid structure. In
      solid phase, FTIR-ATR spectroscopy showed that the CO stretching mode of the TP
      vibrational spectrum changed if the complex between the drug and CyDs occurred.
      This change is temperature-dependent, and its evolution, accounted for by
      deconvolution procedures, provided the thermodynamic parameters explaining the
      mechanisms involved in the formation of inclusion complexes.

PMID- 29042337
TI  - PLGA-PEG nanoparticles for targeted delivery of the mTOR/PI3kinase inhibitor
      dactolisib to inflamed endothelium.
AB  - Dactolisib (NVP-BEZ235, also referred to as: 'BEZ235' or 'BEZ') is a dual
      mTOR/PI3K inhibitor that is of potential interest in the treatment of
      inflammatory disorders. This work focuses on formulation of BEZ-loaded polymeric
      nanoparticles composed of a blend of poly(D,L-lactide-co-glycolide) (PLGA) and
      poly(D,L-lactide-co-glycolide)-poly(ethylene glycol)-2000 (PLGA-PEG). The
      nanoparticles were prepared by an oil/water emulsion solvent evaporation method,
      and were subsequently characterized for yield, encapsulation efficiency,
      morphology, particle size, drug-polymer interaction and in vitro drug release
      profiles. A targeted formulation was developed by conjugation of a S-acetyl
      thioacetyl (SATA)-modified mouse-anti human E-selectin antibody to the distal end
      of PLGA-PEG-SPDP containing nanoparticles. Our results show the successful
      preparation of spherical PLGA/PLGA-PEG nanoparticles loaded with BEZ. The
      particle size distribution showed a range from 250 to 360nm with a high (>75%)
      BEZ encapsulation efficiency. Approximately 35% of the loaded BEZ was released
      within 10days at 37 degrees C in a medium containing 5% bovine serum albumin
      (BSA). Evaluation of efficacy of anti-E-selectin decorated BEZ-loaded
      nanoparticles was carried out in tumor necrosis factor-alpha (TNF-alpha)
      activated endothelial cells. Confocal microscopy analysis showed that cellular
      uptake of the targeted nanoparticles and subsequent internalization. Cell
      functional assays, including migration assay and phosphowestern blot analysis of
      the mTOR and pI3K signaling pathways, revealed that the E-selectin targeted
      nanoparticles loaded with BEZ had a pronounced effect on inflammation-activated
      endothelial cells as compared to the non-targeted BEZ-loaded nanoparticles. In
      conclusion, E-selectin targeted nanoparticles have a high potential in delivering
      the potent mTOR/pI3K inhibitor dactolisib to inflamed endothelial cells and are
      an interesting nanomedicine for anti-inflammatory therapy.

PMID- 29042338
TI  - Drug-resistant Mycobacterium tuberculosis: Epidemiology and role of morphological
      alterations.
AB  - In this brief review, various forms of drug-resistant tuberculosis (DR-TB) are
      discussed. The focus of the study is to highlight morphological alterations of DR
      TB bacilli at the cellular level.

PMID- 29042339
TI  - Clonal dissemination of OXA-48-producing Enterobacter cloacae isolates from
      companion animals in Algeria.
AB  - OBJECTIVES: The aim of this study was to investigate carbapenemase-producing
      Enterobacteriaceae (CPE) in companion animals. METHODS: Between October 2015 and
      April 2016, 533 rectal swabs were obtained from healthy and diseased pets in
      different cities in Algeria. Samples were plated on MacConkey agar supplemented
      with ertapenem (0.5mg/L). Isolates were identified by matrix-assisted laser
      desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS).
      Antimicrobial susceptibility testing was performed by the disk diffusion method.
      Carbapenemase, plasmid-mediated AmpC (pAmpC), extended-spectrum beta-lactamase
      (ESBL) and plasmid-mediated quinolone resistance genes were characterised by PCR.
      Plasmids were extracted by the Kieser extraction method and were analysed by PCR
      based replicon typing (PBRT). The epidemiological relationship between
      Enterobacter cloacae isolates was determined by random amplified polymorphic DNA
      (RAPD) analysis and multilocus sequence typing (MLST). RESULTS: From 533 rectal
      swabs, 12 Enterobacteriaceae (2.3%), including 2 Escherichia coli, 2 Klebsiella
      pneumoniae and 8 E. cloacae, were recovered from selection plates. The 12 strains
      were resistant to amoxicillin/clavulanic acid, ticarcillin,
      piperacillin/tazobactam and ertapenem. All isolates were susceptible to
      aminoglycosides, imipenem and extended-spectrum cephalosporins. PCR and
      sequencing identified the blaOXA-48 gene in all isolates. qnrB1 was identified in
      all E. cloacae isolates. Plasmid analysis showed that the blaOXA-48 gene was
      localised on a 7-kb untypeable plasmid. RAPD analysis demonstrated the presence
      of the same profile pattern in the eight E. cloacae isolates. MLST analysis
      showed that the E. cloacae isolates belonged to ST527. CONCLUSIONS: This study
      reports for the first time the presence of CPE in horses and pet birds in the
      world.

PMID- 29042340
TI  - Mental and Emotional Self-Help Technology Apps: Cross-Sectional Study of Theory,
      Technology, and Mental Health Behaviors.
AB  - BACKGROUND: Mental and emotional self-help apps have emerged as potential mental
      illness prevention and treatment tools. The health behavior theory mechanisms by
      which these apps influence mental health-related behavior change have not been
      thoroughly examined. OBJECTIVE: The objective of this study was to examine the
      association between theoretical behavior change mechanisms and use of mental and
      emotional self-help apps and whether the use of such apps is associated with
      mental health behaviors. METHODS: This study utilized a cross-sectional survey of
      150 users of mental or emotional health apps in the past 6 months. Survey
      questions included theory-based items, app engagement and likeability items, and
      behavior change items. Stata version 14 was used to calculate all statistics.
      Descriptive statistics were calculated for each of the demographic, theory,
      engagement, and behavior variables. Multiple regression analysis was used to
      identify factors associated with reported changes in theory and separately for
      reported changes in actual behavior after controlling for potentially confounding
      variables. RESULTS: Participants reported that app use increased their
      motivation, desire to set goals, confidence, control, and intentions to be
      mentally and emotionally healthy. Engagement (P<.001) was positively associated
      with the reported changes in theory items, whereas perceived behavior change was
      positively associated with theory (P<.001), engagement (P=.004), frequency of use
      of apps (P=.01), and income (P=.049). CONCLUSIONS: Participants reported that app
      use increased their motivation, desire to set goals, confidence, control, and
      intentions to be mentally and emotionally healthy. This increase in perceptions,
      beliefs, and attitudes surrounding their mental and emotional health was
      considerably associated with perceived change in behavior. There was a positive
      association between the level of engagement with the app and the impact on theory
      items. Future efforts should consider the value of impacting key theoretical
      constructs when designing mental and emotional health apps. As apps are evaluated
      and additional theory-based apps are created, cost-effective self-help apps may
      become common preventative and treatment tools in the mental health field.

PMID- 29042341
TI  - Pain Self-Management for Veterans: Development and Pilot Test of a Stage-Based
      Mobile-Optimized Intervention.
AB  - BACKGROUND: Chronic pain is a significant public health burden affecting more
      Americans than cardiovascular disease, diabetes, and cancer combined. Veterans
      are disproportionately affected by chronic pain. Among previously deployed
      soldiers and veterans, the prevalence of chronic pain is estimated between 44%
      and 60%. OBJECTIVE: The objective of this research was to develop and pilot-test
      Health eRide: Your Journey to Managing Pain, a mobile pain self-management
      program for chronic musculoskeletal pain for veterans. Based on the
      transtheoretical model of behavior change, the intervention is tailored to
      veterans' stage of change for adopting healthy strategies for pain self
      management and their preferred strategies. It also addresses stress management
      and healthy sleep, two components of promising integrated treatments for veterans
      with pain and co-occurring conditions, including posttraumatic stress disorder
      (PTSD) and traumatic brain injury. In addition, Health eRide leverages gaming
      principles, text messaging (short message service, SMS), and social networking to
      increase engagement and retention. METHODS: Pilot test participants were 69
      veterans recruited in-person and by mail at a Veterans Health Administration
      facility, by community outreach, and by a Web-based survey company. Participants
      completed a mobile-delivered baseline assessment and Health eRide intervention
      session. During the next 30 days, they had access to a Personal Activity Center
      with additional stage-matched activities and information and had the option of
      receiving tailored text messages. Pre-post assessments, administered at baseline
      and the 30-day follow-up, included measures of pain, pain impact, use of pain
      self-management strategies, PTSD, and percentage in the Action or Maintenance
      stage for adopting pain self-management, managing stress, and practicing healthy
      sleep habits. Global impressions of change and program acceptability and
      usability were also assessed at follow-up. RESULTS: Among the 44 veterans who
      completed the 30-day post assessment, there were statistically significant pre
      post reductions in pain (P<.001) and pain impact (P<.001); there was some
      reduction in symptoms of PTSD (P=.05). There were significant pre-post increases
      in the percentage of participants in the Action or Maintenance stage for adopting
      pain self-management (P=.01) and for managing stress (P<.001) but not for
      practicing healthy sleep habits (P=.11). The global impressions of change measure
      showed that a majority had experienced some level of improvement. User ratings of
      acceptability were quite high; ratings of usability fell slightly below the mean
      for digital programs. CONCLUSIONS: Preliminary data demonstrate the potential
      impact of the Health eRide program for chronic musculoskeletal pain for veterans.
      The results underscore that simultaneously addressing other behaviors may be a
      promising approach to managing pain and comorbid conditions. Additional formative
      research is required to complete development of the Health eRide program and to
      address areas of usability requiring improvement. A randomized trial with longer
      follow-up is needed to demonstrate the program's long-term effects on pain and
      pain self-management.

PMID- 29042342
TI  - Reduction in Fall Rate in Dementia Managed Care Through Video Incident Review:
      Pilot Study.
AB  - BACKGROUND: Falls of individuals with dementia are frequent, dangerous, and
      costly. Early detection and access to the history of a fall is crucial for
      efficient care and secondary prevention in cognitively impaired individuals.
      However, most falls remain unwitnessed events. Furthermore, understanding why and
      how a fall occurred is a challenge. Video capture and secure transmission of real
      world falls thus stands as a promising assistive tool. OBJECTIVE: The objective
      of this study was to analyze how continuous video monitoring and review of falls
      of individuals with dementia can support better quality of care. METHODS: A pilot
      observational study (July-September 2016) was carried out in a Californian memory
      care facility. Falls were video-captured (24*7), thanks to 43 wall-mounted
      cameras (deployed in all common areas and in 10 out of 40 private bedrooms of
      consenting residents and families). Video review was provided to facility staff,
      thanks to a customized mobile device app. The outcome measures were the count of
      residents' falls happening in the video-covered areas, the acceptability of video
      recording, the analysis of video review, and video replay possibilities for care
      practice. RESULTS: Over 3 months, 16 falls were video-captured. A drop in fall
      rate was observed in the last month of the study. Acceptability was good. Video
      review enabled screening for the severity of falls and fall-related injuries.
      Video replay enabled identifying cognitive-behavioral deficiencies and
      environmental circumstances contributing to the fall. This allowed for secondary
      prevention in high-risk multi-faller individuals and for updated facility care
      policies regarding a safer living environment for all residents. CONCLUSIONS:
      Video monitoring offers high potential to support conventional care in memory
      care facilities.

PMID- 29042343
TI  - Systems-Based Training in Graduate Medical Education for Service Learning in the
      State Legislature in the United States: Pilot Study.
AB  - BACKGROUND: There is a dearth of advocacy training in graduate medical education
      in the United States. To address this void, the Legislative Education and
      Advocacy Development (LEAD) course was developed as an interprofessional
      experience, partnering a cohort of pediatrics residents, fourth-year medical
      students, and public health students to be trained in evidence-informed health
      policy making. OBJECTIVE: The objective of our study was to evaluate the
      usefulness and acceptability of a service-based legislative advocacy course.
      METHODS: We conducted a pilot study using a single-arm pre-post study design with
      10 participants in the LEAD course. The course's didactic portion taught learners
      how to define policy problems, research the background of the situation,
      brainstorm solutions, determine evaluation criteria, develop communication
      strategies, and formulate policy recommendations for state legislators. Learners
      worked in teams to create and present policy briefs addressing issues submitted
      by participating Illinois State legislators. We compared knowledge and attitudes
      of learners from pre- and postcourse surveys. We obtained qualitative feedback
      from legislators and pediatric residency directors. RESULTS: Self-reported
      understanding of the health care system increased (mean score from 4 to 3.3,
      P=.01), with answers scored from 1=highly agree to 5=completely disagree. Mean
      knowledge-based scores improved (6.8/15 to 12.0/15 correct). Pediatric residency
      program directors and state legislators provided positive feedback about the LEAD
      course. CONCLUSIONS: Promising results were demonstrated for the LEAD approach to
      incorporate advocacy training into graduate medical education.

PMID- 29042344
TI  - Mommio's Recipe Box: Assessment of the Cooking Habits of Mothers of Preschoolers
      and Their Perceptions of Recipes for a Video Game.
AB  - BACKGROUND: Vegetables are an important part of a healthy diet because they help
      prevent several chronic diseases. Mothers of preschoolers reported difficulty
      getting their young children to eat vegetables, and many did not know how to cook
      child-pleasing recipes. OBJECTIVE: The cooking habits of mothers of preschoolers,
      their perceptions of recipes designed for their children, and the involvement of
      their children in food preparation were assessed to inform a food parenting video
      game called Mommio. METHODS: A cross-sectional survey design was used.
      Eligibility criteria included mothers of 3- to 5-year-old children who reported
      difficulty getting their children to eat vegetables. Participants completed a
      demographic questionnaire with questions about their food preparation practices.
      They were asked to select up to 4 of the 10 provided recipes they wanted to try
      and to prepare and report back on their experiences. RESULTS: Most (46) of the 50
      recipes included in Mommio's in-game recipe box were evaluated at least once and
      some up to 5 times with a total of 85 evaluations. This well-educated, mostly
      employed, sample of 27 mothers of preschoolers preferred simple, quick recipes.
      They ate primarily at home, made dinners from scratch, and indicated that the 46
      recipes were generally simple, quick, and easy to prepare. Involvement in
      preparation enhanced their child's acceptance of the food. Prior food and
      preparation preferences influenced the children's acceptance of the dish at the
      ensuing meal. CONCLUSIONS: The high rate of home recipe preparation indicated
      that including a recipe selection and preparation component in a food parenting
      video game could be attractive and may enhance effectiveness. Mothers reported
      that the recipes provided were generally easy to prepare, tasted good, and the
      instructions were easy to understand, suggesting they could be helpful to the
      mothers when playing a vegetable parenting game. Some mothers reported that
      involving their children in recipe preparation influenced their children's
      willingness to eat the vegetables. The highest rated recipes are being included
      in the game, and mothers will be encouraged to involve their children in recipe
      preparation.

PMID- 29042347
TI  - Online screening test for depression is inappropriate.

PMID- 29042345
TI  - The Association of Patient Factors, Digital Access, and Online Behavior on
      Sustained Patient Portal Use: A Prospective Cohort of Enrolled Users.
AB  - BACKGROUND: As electronic health records and computerized workflows expand, there
      are unprecedented opportunities to digitally connect with patients using secure
      portals. To realize the value of patient portals, initial reach across
      populations will need to be demonstrated, as well as sustained usage over time.
      OBJECTIVE: The study aim was to identify patient factors associated with short
      term and long-term portal usage after patients registered to access all portal
      functions. METHODS: We prospectively followed a cohort of patients at a large
      Department of Veterans Affairs (VA) health care facility who recently completed
      identity proofing to use the VA patient portal. Information collected at baseline
      encompassed patient factors potentially associated with portal usage, including:
      demographics, Internet access and use, health literacy, patient activation, and
      self-reported health conditions. The primary outcome was the frequency of portal
      log-ins during 6-month and 18-month time intervals after study enrollment.
      RESULTS: A total of 270 study participants were followed prospectively. Almost
      all participants (260/268, 97.0%) reported going online, typically at home
      (248/268, 92.5%). At 6 months, 84.1% (227/270) of participants had visited the
      portal, with some variation in usage across demographic and health-related
      subgroups. There were no significant differences in portal log-ins by age,
      gender, education, marital status, race/ethnicity, distance to a VA facility, or
      patient activation measure. Significantly higher portal usage was seen among
      participants using high-speed broadband at home, greater self-reported ability
      using the Internet, and routinely going online. By 18 months, 91% participants
      had logged in to the portal, and no significant associations were found between
      usage and demographics, health status, or patient activation. When examining
      portal activity between 6 and 18 months, patients who were infrequent or high
      portal users remained in those categories, respectively. CONCLUSIONS: Short-term
      and long-term portal usage was associated with having broadband at home, high
      self-rated ability when using the Internet, and overall online behavior. Digital
      inclusion, or ready access to the Internet and digital skills, appears to be a
      social determinant in patient exposure to portal services.

PMID- 29042348
TI  - The future of the Quality and Outcomes Framework in England.

PMID- 29042349
TI  - A junior doctor by any other name.

PMID- 29042351
TI  - Health leaders blame addiction for US opioid crisis.

PMID- 29042352
TI  - Using the power of the media to reduce the risk of suicide.

PMID- 29042353
TI  - Will markets be master or servant to health at the World Bank?

PMID- 29042355
TI  - In This Issue: October.

PMID- 29042354
TI  - Comparison Between Patent Ductus Arteriosus Stent and Modified Blalock-Taussig
      Shunt as Palliation for Infants With Ductal-Dependent Pulmonary Blood Flow:
      Insights From the Congenital Catheterization Research Collaborative.
AB  - BACKGROUND: Infants with ductal-dependent pulmonary blood flow may undergo
      palliation with either a patent ductus arteriosus (PDA) stent or a modified
      Blalock-Taussig (BT) shunt. A balanced multicenter comparison of these 2
      approaches is lacking. METHODS: Infants with ductal-dependent pulmonary blood
      flow palliated with either a PDA stent or a BT shunt from January 2008 to
      November 2015 were reviewed from the 4 member centers of the Congenital
      Catheterization Research Collaborative. Outcomes were compared by use of
      propensity score adjustment to account for baseline differences between groups.
      RESULTS: One hundred six patients with a PDA stent and 251 patients with a BT
      shunt were included. The groups differed in underlying anatomy (expected 2
      ventricle circulation in 60% of PDA stents versus 45% of BT shunts; P=0.001) and
      presence of antegrade pulmonary blood flow (61% of PDA stents versus 38% of BT
      shunts; P<0.001). After propensity score adjustment, there was no difference in
      the hazard of the primary composite outcome of death or unplanned reintervention
      to treat cyanosis (hazard ratio, 0.8; 95% confidence interval [CI], 0.52-1.23;
      P=0.31). Other reinterventions were more common in the PDA stent group (hazard
      ratio, 29.8; 95% CI, 9.8-91.1; P<0.001). However, the PDA stent group had a lower
      adjusted intensive care unit length of stay (5.3 days [95% CI, 4.2-6.7] versus
      9.19 days [95% CI, 7.9-10.6]; P<0.001), a lower risk of diuretic use at discharge
      (odds ratio, 0.4; 95% CI, 0.25-0.64; P<0.001) and procedural complications (odds
      ratio, 0.4; 95% CI, 0.2-0.77; P=0.006), and larger (152 mm2/m2 [95% CI, 132-176]
      versus 125 mm2/m2 [95% CI, 113-138]; P=0.029) and more symmetrical (symmetry
      index, 0.84 [95% CI, 0.8-0.89] versus 0.77 [95% CI, 0.75-0.8]; P=0.008] pulmonary
      arteries at the time of subsequent surgical repair or last follow-up.
      CONCLUSIONS: In this multicenter comparison of palliative PDA stent and BT shunt
      for infants with ductal-dependent pulmonary blood flow adjusted for differences
      in patient factors, there was no difference in the primary end point, death or
      unplanned reintervention to treat cyanosis. However, other markers of morbidity
      and pulmonary artery size favored the PDA stent group, supporting PDA stent as a
      reasonable alternative to BT shunt in select patients.

PMID- 29042356
TI  - State of health and care in England.

PMID- 29042357
TI  - David Oliver: Challenging the victim narrative about NHS doctors.

PMID- 29042359
TI  - Focus on physical activity can help avoid unnecessary social care.

PMID- 29042358
TI  - Safety, immunogenicity and efficacy after switching from reference infliximab to
      biosimilar SB2 compared with continuing reference infliximab and SB2 in patients
      with rheumatoid arthritis: results of a randomised, double-blind, phase III
      transition study.
AB  - OBJECTIVES: Efficacy, safety and immunogenicity results from the phase III study
      of SB2, a biosimilar of reference infliximab (INF), were previously reported
      through 54 weeks. This transition period compared results in patients with
      rheumatoid arthritis (RA) who switched from INF to SB2 with those in patients who
      maintained treatment with INF or SB2. METHODS: Patients with moderate to severe
      RA despite methotrexate treatment were randomised (1:1) to receive SB2 or INF at
      weeks 0, 2 and 6 and every 8 weeks thereafter until week 46. At week 54, patients
      previously receiving INF were rerandomised (1:1) to switch to SB2 (INF/SB2
      (n=94)) or to continue on INF (INF/INF (n=101)) up to week 70. Patients
      previously receiving SB2 continued on SB2 (SB2/SB2 (n=201)) up to week 70.
      Efficacy, safety and immunogenicity were assessed up to week 78. RESULTS:
      Efficacy was sustained and comparable across treatment groups. American College
      of Rheumatology (ACR) 20 responses between weeks 54 and 78 ranged from 63.5% to
      72.3% with INF/SB2, 66.3%%-69.4% with INF/INF and 65.6%-68.3% with SB2/SB2.
      Treatment-emergent adverse events during this time occurred in 36.2%, 35.6% and
      40.3%, respectively, and infusion-related reactions in 3.2%, 2.0% and 3.5%. Among
      patients who were negative for antidrug antibodies (ADA) up to week 54, newly
      developed ADAs were reported in 14.6%, 14.9% and 14.1% of the INF/SB2, INF/INF
      and SB2/SB2 groups, respectively. CONCLUSIONS: The efficacy, safety and
      immunogenicity profiles remained comparable among the INF/SB2, INF/INF and
      SB2/SB2 groups up to week 78, with no treatment-emergent issues or clinically
      relevant immunogenicity after switching from INF to SB2. TRIAL REGISTRATION
      NUMBER: NCT01936181; EudraCT number: 2012-005733-37.

PMID- 29042361
TI  - Sixty seconds on . . . runny eggs.

PMID- 29042363
TI  - Can we usefully stratify patients according to suicide risk?

PMID- 29042362
TI  - Comparative safety of direct oral anticoagulants and warfarin in venous
      thromboembolism: multicentre, population based, observational study.
AB  - Objective To determine the safety of direct oral anticoagulant (DOAC) use
      compared with warfarin use for the treatment of venous thromboembolism.Design
      Retrospective matched cohort study conducted between 1 January 2009 and 31 March
      2016.Setting Community based, using healthcare data from six jurisdictions in
      Canada and the United States.Participants 59 525 adults (12 489 DOAC users; 47
      036 warfarin users) with a new diagnosis of venous thromboembolism and a
      prescription for a DOAC or warfarin within 30 days of diagnosis.Main outcome
      measures Outcomes included hospital admission or emergency department visit for
      major bleeding and all cause mortality within 90 days after starting treatment.
      Propensity score matching and shared frailty models were used to estimate
      adjusted hazard ratios of the outcomes comparing DOACs with warfarin. Analyses
      were conducted independently at each site, with meta-analytical methods used to
      estimate pooled hazard ratios across sites.Results Of the 59 525 participants,
      1967 (3.3%) had a major bleed and 1029 (1.7%) died over a mean follow-up of 85.2
      days. The risk of major bleeding was similar for DOAC compared with warfarin use
      (pooled hazard ratio 0.92, 95% confidence interval 0.82 to 1.03), with the
      overall direction of the association favouring DOAC use. No difference was found
      in the risk of death (pooled hazard ratio 0.99, 0.84 to 1.16) for DOACs compared
      with warfarin use. There was no evidence of heterogeneity across centres, between
      patients with and without chronic kidney disease, across age groups, or between
      male and female patients.Conclusions In this analysis of adults with incident
      venous thromboembolism, treatment with DOACs, compared with warfarin, was not
      associated with an increased risk of major bleeding or all cause mortality in the
      first 90 days of treatment.Trial registration Clinical trials NCT02833987.

PMID- 29042364
TI  - A CD200R-CD28 fusion protein appropriates an inhibitory signal to enhance T-cell
      function and therapy of murine leukemia.
AB  - Acute myeloid leukemia (AML), the most common adult acute leukemia in the United
      States, has the poorest survival rate, with 26% of patients surviving 5 years.
      Adoptive immunotherapy with T cells genetically modified to recognize tumors is a
      promising and evolving treatment option. However, antitumor activity,
      particularly in the context of progressive leukemia, can be dampened both by
      limited costimulation and triggering of immunoregulatory checkpoints that
      attenuate T-cell responses. Expression of CD200 (OX2), a negative regulator of T
      cell function that binds CD200 receptor (CD200R), is commonly increased in
      leukemia and other malignancies and is associated with poor prognosis in leukemia
      patients. To appropriate and redirect the inhibitory effects of CD200R signaling
      on transferred CD8+ T cells, we engineered CD200R immunomodulatory fusion
      proteins (IFPs) with the cytoplasmic tail replaced by the signaling domain of the
      costimulatory receptor, CD28. An analysis of a panel of CD200R-CD28 IFP
      constructs revealed that the most effective costimulation was achieved in IFPs
      containing a dimerizing motif and a predicted tumor-T-cell distance that
      facilitates localization to the immunological synapse. T cells transduced with
      the optimized CD200R-CD28 IFPs exhibited enhanced proliferation and effector
      function in response to CD200+ leukemic cells in vitro. In adoptive therapy of
      disseminated leukemia, CD200R-CD28-transduced leukemia-specific CD8 T cells
      eradicated otherwise lethal disease more efficiently than wild-type cells and
      bypassed the requirement for interleukin-2 administration to sustain in vivo
      activity. The transduction of human primary T cells with the equivalent human
      IFPs increased proliferation and cytokine production in response to CD200+
      leukemia cells, supporting clinical translation. This trial was registered at
      www.clinicaltrials.gov as #NCT01640301.

PMID- 29042365
TI  - Ruxolitinib-induced defects in DNA repair cause sensitivity to PARP inhibitors in
      myeloproliferative neoplasms.
AB  - Myeloproliferative neoplasms (MPNs) often carry JAK2(V617F), MPL(W515L), or
      CALR(del52) mutations. Current treatment options for MPNs include cytoreduction
      by hydroxyurea and JAK1/2 inhibition by ruxolitinib, both of which are not
      curative. We show here that cell lines expressing JAK2(V617F), MPL(W515L), or
      CALR(del52) accumulated reactive oxygen species-induced DNA double-strand breaks
      (DSBs) and were modestly sensitive to poly-ADP-ribose polymerase (PARP)
      inhibitors olaparib and BMN673. At the same time, primary MPN cell samples from
      individual patients displayed a high degree of variability in sensitivity to
      these drugs. Ruxolitinib inhibited 2 major DSB repair mechanisms, BRCA-mediated
      homologous recombination and DNA-dependent protein kinase-mediated nonhomologous
      end-joining, and, when combined with olaparib, caused abundant accumulation of
      toxic DSBs resulting in enhanced elimination of MPN primary cells, including the
      disease-initiating cells from the majority of patients. Moreover, the combination
      of BMN673, ruxolitinib, and hydroxyurea was highly effective in vivo against
      JAK2(V617F)+ murine MPN-like disease and also against JAK2(V617F)+, CALR(del52)+,
      and MPL(W515L)+ primary MPN xenografts. In conclusion, we postulate that
      ruxolitinib-induced deficiencies in DSB repair pathways sensitized MPN cells to
      synthetic lethality triggered by PARP inhibitors.

PMID- 29042366
TI  - Emicizumab, a bispecific antibody recognizing coagulation factors IX and X: how
      does it actually compare to factor VIII?
AB  - During the last decade, the development of improved and novel approaches for the
      treatment of hemophilia A has expanded tremendously. These approaches include
      factor VIII (FVIII) with extended half-life (eg, FVIII-Fc and PEGylated FVIII),
      monoclonal antibodies targeting tissue factor pathway inhibitor, small
      interfering RNA to reduce antithrombin expression and the bispecific antibody
      ACE910/emicizumab. Emicizumab is a bispecific antibody recognizing both the
      enzyme factor IXa and the substrate factor X. By simultaneously binding enzyme
      and substrate, emicizumab mimics some part of the function exerted by the
      original cofactor, FVIII, in that it promotes colocalization of the enzyme
      substrate complex. However, FVIII and the bispecific antibody are fundamentally
      different proteins and subject to different modes of regulation. Here, we will
      provide an overview of the similarities and dissimilarities between FVIII and
      emicizumab from a biochemical and mechanistical perspective. Such insight might
      be useful in the clinical decision making for those who apply emicizumab in their
      practice now or in the future, particularly in view of the thrombotic
      complications that have been reported when emicizumab is used in combination with
      FVIII-bypassing agents.

PMID- 29042368
TI  - Injecting drug use continues in older drug users too.

PMID- 29042367
TI  - Safety and efficacy of long-term treatment of chronic/persistent ITP with
      eltrombopag: final results of the EXTEND study.
AB  - In phase 2/3 trials, eltrombopag treatment of 6 months or less in patients with
      chronic/persistent immune thrombocytopenia (ITP) increased platelet counts and
      reduced bleeding. The open-label EXTEND study evaluated long-term safety and
      efficacy of eltrombopag in adults with ITP who had completed a previous
      eltrombopag study. For the 302 patients enrolled, median duration of eltrombopag
      treatment was 2.37 years (2 days-8.76 years). Median platelet counts increased to
      50 * 109/L or more by week 2 and were sustained throughout the treatment period.
      Overall, 259 patients (85.8%) achieved a response (platelet count >=50 * 109/L at
      least once in the absence of rescue), and 133 (52%) of 257 patients achieved a
      continuous response of 25 weeks or longer. Responses in patients with platelet
      counts lower than 15 * 109/L, more previous therapies, and/or splenectomy were
      somewhat lower. Thirty-four (34%) of 101 patients receiving concomitant ITP
      medication discontinued 1 or more medication. In patients with assessments,
      bleeding symptoms (World Health Organization grades 1-4) decreased from 57% at
      baseline to 16% at 1 year. Forty-one patients (14%) withdrew because of adverse
      events. Hepatobiliary adverse events (n = 7), cataracts (n = 4), deep vein
      thrombosis (n = 3), cerebral infarction (n = 2), headache (n = 2), and
      myelofibrosis (n = 2) occurred in more than 1 patient; the remaining adverse
      events occurred only once. Rates of thromboembolic events (6%) and hepatobiliary
      adverse events (15%) did not increase with treatment duration past 1 year. EXTEND
      demonstrated that long-term use of eltrombopag was effective in maintaining
      platelet counts of 50 * 109/L or more and reducing bleeding in most patients with
      ITP of more than 6 months' duration. Important adverse events (eg, thrombosis,
      hepatobiliary, and bone marrow fibrosis) were infrequent.
      (ClinicalTrials.gov:NCT00351468).

PMID- 29042369
TI  - NHS boss reveals loss of further 162 000 pieces of medical correspondence.

PMID- 29042370
TI  - Mandated reporters' experiences with reporting child maltreatment: a meta
      synthesis of qualitative studies.
AB  - OBJECTIVE: To systematically search for research about the effectiveness of
      mandatory reporting of child maltreatment and to synthesise qualitative research
      that explores mandated reporters' (MRs) experiences with reporting. DESIGN: As no
      studies assessing the effectiveness of mandatory reporting were retrieved from
      our systematic search, we conducted a meta-synthesis of retrieved qualitative
      research. Searches in Medline (Ovid), Embase, PsycINFO, Cumulative Index to
      Nursing and Allied Health Literature, Sociological Abstracts, Education Resources
      Information Center, Criminal Justice Abstracts and Cochrane Library yielded over
      6000 citations, which were deduplicated and then screened by two independent
      reviewers. English-language, primary qualitative studies that investigated MRs'
      experiences with reporting of child maltreatment were included. Critical
      appraisal involved a modified checklist from the Critical Appraisal Skills
      Programme and qualitative meta-synthesis was used to combine results from the
      primary studies. SETTING: All healthcare and social-service settings implicated
      by mandatory reporting laws were included. Included studies crossed nine high
      income countries (USA, Australia, Sweden, Taiwan, Canada, Norway, Finland, Israel
      and Cyprus) and three middle-income countries (South Africa, Brazil and El
      Salvador). PARTICIPANTS: The studies represent the views of 1088 MRs. OUTCOMES:
      Factors that influence MRs' decision to report and MRs' views towards and
      experiences with mandatory reporting of child maltreatment. RESULTS: Forty-four
      articles reporting 42 studies were included. Findings indicate that MRs struggle
      to identify and respond to less overt forms of child maltreatment. While some
      articles (14%) described positive experiences MRs had with the reporting process,
      negative experiences were reported in 73% of articles and included accounts of
      harm to therapeutic relationships and child death following removal from their
      family of origin. CONCLUSIONS: The findings of this meta-synthesis suggest that
      there are many potentially harmful experiences associated with mandatory
      reporting and that research on the effectiveness of this process is urgently
      needed.

PMID- 29042371
TI  - Better early functional outcome after short stem total hip arthroplasty? A
      prospective blinded randomised controlled multicentre trial comparing the Collum
      Femoris Preserving stem with a Zweymuller straight cementless stem total hip
      replacement for the treatment of primary osteoarthritis of the hip.
AB  - OBJECTIVES: Primary aim was to compare the functional results at 3 months and 2
      years between short and conventional cementless stem total hip arthroplasty
      (THA). Secondary aim was to determine the feasibility of a double-blind implant
      related trial. DESIGN: A prospective blinded randomised controlled multicentre
      trial in patients with osteoarthritis of the hip. All patients, research
      assistants, clinical assessors, investigators and data analysts were blinded to
      the type of prosthesis. POPULATION: 150 patients between 18 and 70 years with
      osteoarthritis of the hip, 75 in the short stem and 75 in the conventional stem
      group. Mean age: 60 years (SD 7). INTERVENTIONS: the Collum Femoris Preserving
      short stem versus the Zweymuller Alloclassic conventional stem. MAIN OUTCOME
      MEASURES: The Dutch version of the Hip Disability and Osteoarthritis Outcome
      Score (HOOS). Secondary outcomes measures: Harris Hip Score, the Physical
      Component Scale of the SF12, the Timed Up and Go test, Pain and the EQ-5D.
      Feasibility outcomes: continued blinding, protocol adherence and follow-up
      success rate. RESULTS: No significant difference between the two groups. Mean
      HOOS total score in the short stem group increased 32.7 points from 36.6 (95% CI
      32.9 to 40.2) preoperatively to 69.3 (95% CI 66.4 to 72.1) at 3 months follow-up.
      Mean HOOS total score in the conventional straight stem group increased 36.3
      points from 37.1 (95% CI 33.9 to 40.3) preoperatively to 73.4 (95% CI 70.3 to
      76.4) at 3 months follow-up. 91.2% of patients remained blinded at 2 years follow
      up. Both protocol adherence and follow-up success rate were 98%. CONCLUSIONS:
      Functional result at 3 months and 2 years after short stem THA is not superior to
      conventional cementless THA. There were more perioperative and postoperative
      complications in the short stem group. Direct comparison of two hip implants in a
      double-blinded randomised controlled trial is feasible. TRIAL REGISTRATION
      NUMBER: NTR1560.

PMID- 29042372
TI  - Awareness and willingness towards pre-exposure prophylaxis against HIV infection
      among individuals seeking voluntary counselling and testing for HIV in Taiwan: a
      cross-sectional questionnaire survey.
AB  - OBJECTIVES: We aimed to investigate the awareness and willingness towards pre
      exposure prophylaxis (PrEP) among individuals seeking voluntary counselling and
      testing (VCT) for HIV in Taiwan, where PrEP is currently not reimbursed by the
      insurance. METHODS: Between April and October 2016, a questionnaire interview was
      conducted among VCT clients to inquire about the attitudes towards PrEP against
      HIV infection. Multivariate logistic regression analysis was performed to
      identify the associated factors with willingness to initiate PrEP. RESULTS:
      During the 6-month period, 1173 VCT clients (99.8%) completed the interviews,
      with 67.4% being homosexual or bisexual male. While 67.2% of the clients knew of
      postexposure prophylaxis, 40.2% heard of PrEP. Overall, 546 clients (46.5%) were
      willing to initiate PrEP and 89.5% of them would choose event-driven PrEP. In
      multivariate analysis, male gender (OR 1.796; 95% CI 1.165 to 2.768), full-time
      job (OR 1.354; 95% CI 1.052 to 1.742), one-night stand (OR 1.374; 95% CI 1.043 to
      1.810), having casual sex partners within 3 months (OR 1.329; 95% CI 1.031 to
      1.714), condomless anal sex (OR 1.405; 95% CI 1.122 to 1.878) and ever having
      chemsex or attending a drug party in the past 1 year (OR 2.571; 95% CI 1.541 to
      4.287), regular screening for HIV infection (OR 1.321; 95% CI 1.021 to 1.711) and
      knowledge of PrEP (OR 1.504; 95% CI, 1.159 to 1.953) were associated with
      willingness to initiate PrEP. CONCLUSIONS: Understanding the willingness to
      initiate PrEP against HIV among the VCT clients in Taiwan, which was associated
      with male gender, risky sexual behaviours and awareness of PrEP, will help inform
      the implementation of PrEP programme.

PMID- 29042373
TI  - Emotional reactions in parents of the youth who experienced the Utoya shooting on
      22 July 2011; results from a cohort study.
AB  - OBJECTIVE AND SETTING: The objective of this study was to provide knowledge about
      the emotional reactions in parents whose offspring experienced a mass shooting on
      Utoya island in Norway in 2011. The research questions included whether parents'
      reactions were influenced by their offspring's symptom level, age, living
      situation and parental gender. DESIGN: The study was designed as an open cohort
      study. The data were collected at two time points; 4-5 months and 14-15 months
      after the shooting. PARTICIPANTS: The participants were 531 parents of youth
      exposed to the Utoya island attack. OUTCOME MEASURES: The Parental Emotional
      Reaction Questionnaire measured parents' reactions, and University of California,
      Los Angeles Post-traumatic Stress Disorder Reaction Index measured youths' post
      traumatic stress symptoms. RESULTS: Parental emotional reactions were positively
      related to post-traumatic stress reactions in offspring at wave 1: Est.=0.20, 95%
      CI 0.10 to 0.30, p<0.001, over time (wave 1and wave 2 nested within individuals):
      Est.=0.23, CI 0.13 to 0.32, p<0.001, and at wave 2: Est.=0.26, CI 0.12 to 0.39,
      p<0.001. Youths' age was not significantly related to parental emotional
      reactions, neither at wave 1: Est.=0.19, CI -0.40 to 0.77, p=0.531, over time:
      Est.=0.26, CI -0.27 to 0.79, p=328, nor at wave 2: Est.=0.32, CI -0.41 to 1.05,
      p=0.389. Mothers were more emotionally upset than fathers both at wave 1: Est.=
      5.66, CI -7.63 to -3.69, p<0.001, over time: Est.=-5.36, CI -7.18 to -3.55,
      p<0.001, and at wave 2: Est.=-5.33, CI -7.72 to -2.53, p<0.001. CONCLUSIONS: The
      findings suggest that parenting after trauma should be addressed in outreach
      programmes and in planning of healthcare services.

PMID- 29042374
TI  - 'What does that mean?': a qualitative exploration of the primary and secondary
      clinical care experiences of young people with continence problems in the UK.
AB  - OBJECTIVES: To explore the clinical care experiences of young people with
      continence problems. DESIGN: In-depth semistructured qualitative interviews were
      conducted by Skype and telephone, with the addition of art-based participatory
      research techniques. Transcripts were analysed using inductive thematic analysis.
      SETTING: Primary and secondary care in the UK. PARTICIPANTS: We interviewed 20
      participants (9 females, 11 males) aged 11-20 years. There were six participants
      with bedwetting alone, five with daytime wetting alone, five with combined (day
      and night) wetting and four with soiling. RESULTS: We identified four themes:
      appointment experiences, treatment experiences, engagement with treatment and
      internalisation and externalisation of the continence problem. Patient-focused
      appointments using age-appropriate language were highly desirable. Continuity of
      care was highlighted as an important aspect of positive clinical experiences;
      however, this was found to be rare with many participants seeing a different
      person on each visit. Participants had tried a wide range of treatments for their
      continence problems with varying degrees of success. Relapse and treatment
      failure were common. Experiencing relapse was distressing and diminished
      participants' belief in the success of future treatments and undermined
      adherence. Participants would be seen to adopt two opposing coping strategies for
      dealing with their continence problem- internalisation and externalisation.
      CONCLUSION: Incontinence in young people is challenging to manage. Young people
      may need to try a range of treatments before their symptoms improve. Due to
      challenges in treatment, there is an increased risk of poor adherence. During
      patient-focused appointments, clinicians should work to build rapport with
      patients and use age-appropriate language. Involving young people in their own
      care decisions is important. The way in which young people understand their
      continence problem can influence their coping strategies and adherence to
      treatment regimes.

PMID- 29042375
TI  - Non-invasive brain stimulation interventions for management of chronic central
      neuropathic pain: a scoping review protocol.
AB  - INTRODUCTION: Pain can affect people regardless of age, gender or ethnicity.
      Chronic central neuropathic pain (CCNP) is a debilitating condition that affects
      populations such as stroke survivors, amputees, spinal cord injury patients and
      patients with multiple sclerosis, with prevalence rates between 30% and 80%. This
      condition can be caused by a lesion or disease affecting the somatosensory
      system. CCNP is notoriously drug resistant, and few effective CCNP treatment or
      management strategies exist. The emergence of non-invasive brain stimulation and
      neuromodulation techniques provide novel avenues for managing chronic central
      neuropathic pain. This scoping review aims to systematically identify the methods
      and effectiveness of non-invasive brain stimulation techniques for treating and
      managing chronic central neuropathic pain. METHODS AND ANALYSIS: The following
      databases will be searched systematically: PubMed, EMBASE, Cumulative Index to
      Nursing and Allied Health Literature (CINAHL), Institute of Electric and
      Electronic Engineers (IEEE), Association of Computing Machinary (ACM) and Scopus.
      Additional literature will be identified by searching the reference lists of
      identified studies. Studies will include reviews and original research in both
      published and grey literatures. Two reviewers will independently screen
      identified studies for final inclusion. A quantitative analysis on the
      intervention type, application and efficacy will be synthesised along with a
      qualitative analysis to describe the effectiveness of each intervention. ETHICS
      AND DISSEMINATION: No primary data will be collected and hence formal ethics
      review is not required. The results of the scoping review will be presented at
      relevant national and international conferences, published in a peer-reviewed
      journal and provided to the stakeholders with plain language to be posted on
      their websites. This scoping review will provide a foundation to guide the
      development of future primary research on non-invasive brain stimulation and
      CCNP.

PMID- 29042377
TI  - Effectiveness and meaningful use of paediatric surgical safety checklists and
      their implementation strategies: a systematic review with narrative synthesis.
AB  - OBJECTIVE: To examine the effectiveness and meaningful use of paediatric surgical
      safety checklists (SSCs) and their implementation strategies through a systematic
      review with narrative synthesis. SUMMARY BACKGROUND DATA: Since the launch of the
      WHO SSC, checklists have been integrated into surgical systems worldwide.
      Information is sparse on how SSCs have been integrated into the paediatric
      surgical environment. METHODS: A broad search strategy was created using Pubmed,
      Embase, CINAHL, Cochrane Central, Web of Science, Science Citation Index and
      Conference Proceedings Citation Index. Abstracts and full texts were screened
      independently, in duplicate for inclusion. Extracted study characteristic and
      outcomes generated themes explored through subgroup analyses and idea webbing.
      RESULTS: 1826 of 1921 studies were excluded after title and abstract review
      (kappa 0.77) and 47 after full-text review (kappa 0.86). 20 studies were of
      sufficient quality for narrative synthesis. Clinical outcomes were not affected
      by SSC introduction in studies without implementation strategies. A comprehensive
      SSC implementation strategy in developing countries demonstrated improved
      outcomes in high-risk surgeries. Narrative synthesis suggests that meaningful
      compliance is inconsistently measured and rarely achieved. Strategies involving
      feedback improved compliance. Stakeholder-developed implementation strategies,
      including team-based education, achieved greater acceptance. Three studies
      suggest that parental involvement in the SSC is valued by parents, nurses and
      physicians and may improve patient safety. CONCLUSIONS: A SSC implementation
      strategy focused on paediatric patients and their families can achieve high
      acceptability and good compliance. SSCs' role in improving measures of paediatric
      surgical outcome is not well established, but they may be effective when used
      within a comprehensive implementation strategy especially for high-risk patients
      in low-resource settings.

PMID- 29042376
TI  - Protocol for a cohort study of adolescent mental health service users with a
      nested cluster randomised controlled trial to assess the clinical and cost
      effectiveness of managed transition in improving transitions from child to adult
      mental health services (the MILESTONE study).
AB  - INTRODUCTION: Disruption of care during transition from child and adolescent
      mental health services (CAMHS) to adult mental health services may adversely
      affect the health and well-being of service users. The MILESTONE (Managing the
      Link and Strengthening Transition from Child to Adult Mental Healthcare) study
      evaluates the longitudinal course and outcomes of adolescents approaching the
      transition boundary (TB) of their CAMHS and determines the effectiveness of the
      model of managed transition in improving outcomes, compared with usual care.
      METHODS AND ANALYSIS: This is a cohort study with a nested cluster randomised
      controlled trial. Recruited CAMHS have been randomised to provide either (1)
      managed transition using the Transition Readiness and Appropriateness Measure
      score summary as a decision aid, or (2) usual care for young people reaching the
      TB. Participants are young people within 1 year of reaching the TB of their CAMHS
      in eight European countries; one parent/carer and a CAMHS clinician for each
      recruited young person; and adult mental health clinician or other community
      based care provider, if young person transitions. The primary outcome is Health
      of the Nation Outcome Scale for Children and Adolescents (HoNOSCA) measuring
      health and social functioning at 15 months postintervention. The secondary
      outcomes include mental health, quality of life, transition experience and
      healthcare usage assessed at 9, 15 and 24 months postintervention. With a mean
      cluster size of 21, a total of 840 participants randomised in a 1:2 intervention
      to control are required, providing 89% power to detect a difference in HoNOSCA
      score of 0.30 SD. The addition of 210 recruits for the cohort study ensures
      sufficient power for studying predictors, resulting in 1050 participants and an
      approximate 1:3 randomisation. ETHICS AND DISSEMINATION: The study protocol was
      approved by the UK National Research Ethics Service (15/WM/0052) and equivalent
      ethics boards in participating countries. Results will be reported at
      conferences, in peer-reviewed publications and to all relevant stakeholder
      groups. TRIAL REGISTRATION NUMBER: ISRCTN83240263; NCT03013595 (pre-results).

PMID- 29042378
TI  - Association between polypharmacy and falls in older adults: a longitudinal study
      from England.
AB  - OBJECTIVES: Assess the longitudinal association between polypharmacy and falls
      and examine the differences in this association by different thresholds for
      polypharmacy definitions in a nationally representative sample of adults aged
      over 60 years from England. DESIGN: Longitudinal cohort study. SETTING: The
      English Longitudinal Study of Ageing waves 6 and 7. PARTICIPANTS: 5213 adults
      aged 60 or older. MAIN OUTCOME MEASURES: Rates, incidence rate ratio (IRR) and
      95% CI for falls in people with and without polypharmacy. RESULTS: A total of
      5213 participants contributed 10 502 person-years of follow-up, with a median
      follow-up of 2.02 years (IQR 1.9-2.1 years). Of the 1611 participants with
      polypharmacy, 569 reported at least one fall within the past 2 years (rate: 175
      per 1000 person-years, 95% CI 161 to 190), and of the 3602 participants without
      polypharmacy 875 reported at least one fall (rate: 121 per 1000 person-years, 95%
      CI 113 to 129). The rate of falls was 21% higher in people with polypharmacy
      compared with people without polypharmacy (adjusted IRR 1.21, 95% CI 1.11 to
      1.31). Using >=4 drugs threshold the rate of falls was 18% higher in people with
      polypharmacy compared with people without (adjusted IRR 1.18, 95% CI 1.08 to
      1.28), whereas using >=10 drugs threshold polypharmacy was associated with a 50%
      higher rate of falls (adjusted IRR 1.50, 95% CI 1.34 to 1.67). CONCLUSIONS: We
      found almost one-third of the total population using five or more drugs, which
      was significantly associated with 21% increased rate of falls over a 2-year
      period. Further exploration of the effects of these complex drug combinations in
      the real world with a detailed standardised assessment of polypharmacy is greatly
      required along with pragmatic studies in primary care, which will help inform
      whether the threshold for a detailed medication review should be lowered.

PMID- 29042379
TI  - Stigma among Singaporean youth: a cross-sectional study on adolescent attitudes
      towards serious mental illness and social tolerance in a multiethnic population.
AB  - OBJECTIVES: Stigma against mental illnesses is one of the significant obstacles
      faced by mental health service users and providers. It can develop at a young age
      and is also influenced by culture. Youths in Southeast Asian countries are under
      represented in mental health research, thus this study aims to explore the
      dimensions of stigma and social tolerance and examine its correlates in the
      younger, multiethnic population of Singapore. DESIGN: An online survey collected
      data with sociodemographic questions, the Attitudes Towards Serious Mental
      Illness (Adolescent version) Scale, Social Tolerance Scale and an open-text
      question on words or phrases participants associated with the term 'mental
      illness'. Principal component analysis and multiple regression models were
      conducted to investigate the factor structure of the attitudes and social
      tolerance scales and their sociodemographic correlates. PARTICIPANTS:
      Participants included 940 youths aged 14-18 years old who were residing in
      Singapore at the time of the survey and were recruited through local schools.
      RESULTS: About a quarter of the students (22.6%) reported participating in mental
      health awareness campaigns while nearly half (44.5%) associated pejorative words
      and phrases with the term mental illness. The Attitudes Towards Serious Mental
      Illness (Adolescent version) Scale yielded five factors while the Social
      Tolerance Scale yielded two. Ethnicity, gender and nationality were significantly
      correlated with factors of both scales. Chinese youths showed higher sense of
      'physical threat' and lower 'social tolerance' than those of other ethnicities.
      Females showed more 'wishful thinking', 'social concern' and 'social
      responsibility' towards the mentally ill than males. CONCLUSIONS: The dimensions
      of stigma and social tolerance are different in Asian cultures compared with
      Western cultures. Sociodemographic differences in attitudes towards the mentally
      ill were found among youths living in Singapore. Misconceptions and negative
      attitudes towards mental illness are common, demonstrating a clear need for
      effective stigma reduction campaigns.

PMID- 29042380
TI  - Potentially inappropriate prescribing and its association with health outcomes in
      middle-aged people: a prospective cohort study in Ireland.
AB  - OBJECTIVES: To determine the prevalence of potentially inappropriate prescribing
      (PIP) in a cohort of community-dwelling middle-aged people and assess the
      relationship between PIP and emergency department (ED) visits, general
      practitioner (GP) visits and quality of life (QoL). DESIGN: Prospective cohort
      study. SETTING: The Irish Longitudinal Study on Ageing (TILDA), a nationally
      representative cohort study of ageing. PARTICIPANTS: Individuals aged 45-64 years
      recruited to TILDA who were eligible for the means-tested General Medical
      Services scheme and followed up after 2 years. EXPOSURE: PIP was determined in
      the 12 months preceding baseline and follow-up TILDA data collection by applying
      the PRescribing Optimally in Middle-aged People's Treatments (PROMPT) criteria to
      participants' medication dispensing data. OUTCOME MEASURES: At follow-up, the
      reported rates of ED and GP visits over 12 months (primary outcome) and the CASP
      R12 (Control Autonomy Self-realisation Pleasure) measure of QoL (secondary
      outcome). ANALYSIS: Multivariate negative binomial (rates) and linear regression
      (CASP-R12) models controlling for potential confounders. RESULTS: At 2-year
      follow-up (n=808), PIP was detected in 42.9% by the PROMPT criteria. An ED visit
      was reported by 18.7% and 94.4% visited a GP (median 4 visits, IQR 2-6). Exposure
      to >=2 PROMPT criteria was associated with higher rates of healthcare utilisation
      and lower QoL in unadjusted regression. However, in multivariate analysis, the
      associations between PIP and rates of ED visits (adjusted incidence rate ratio
      (IRR) 0.92, 95% CI 0.53 to 1.58), and GP visits (IRR 1.06, 95% CI 0.87 to 1.28),
      and CASP-R12 score (adjusted beta coefficient 0.35, 95% CI -0.93 to 1.64) were
      not statistically significant. Numbers of medicines and comorbidities were
      associated with higher healthcare utilisation. CONCLUSIONS: Although PIP was
      prevalent in this study population, there was no evidence of a relationship with
      ED and GP visits and QoL. Further research should evaluate whether the PROMPT
      criteria are related to these and other adverse outcomes in the general middle
      aged population.

PMID- 29042381
TI  - Associations between major chain fast-food outlet availability and change in body
      mass index: a longitudinal observational study of women from Victoria, Australia.
AB  - OBJECTIVES: The residential neighbourhood fast-food environment has the potential
      to lead to increased levels of obesity by providing opportunities for residents
      to consume energy-dense products. This longitudinal study aimed to examine
      whether change in body mass index (BMI) differed dependent on major chain fast
      food outlet availability among women residing in disadvantaged neighbourhoods.
      SETTING: Eighty disadvantaged neighbourhoods in Victoria, Australia.
      PARTICIPANTS: Sample of 882 women aged 18-46 years at baseline (wave I:
      2007/2008) who remained at the same residential location at all three waves (wave
      II: 2010/2011; wave III: 2012/2013) of the Resilience for Eating and Activity
      Despite Inequality study. PRIMARY OUTCOME: BMI based on self-reported height and
      weight at each wave. RESULTS: There was no evidence of an interaction between
      time and the number of major chain fast-food outlets within 2 (p=0.88), 3
      (p=0.66) or 5 km (p=0.24) in the multilevel models of BMI. Furthermore, there was
      no evidence of an interaction between time and change in availability at any
      distance and BMI. CONCLUSIONS: Change in BMI was not found to differ by
      residential major chain fast-food outlet availability among Victorian women
      residing in disadvantaged neighbourhoods. It may be that exposure to fast-food
      outlets around other locations regularly visited influence change in BMI. Future
      research needs to consider what environments are the key sources for accessing
      and consuming fast food and how these relate to BMI and obesity risk.

PMID- 29042382
TI  - Drugs and life-threatening ventricular arrhythmia risk: results from the DARE
      study cohort.
AB  - OBJECTIVES: To establish a unique sample of proarrhythmia cases, determine the
      characteristics of cases and estimate the contribution of individual drugs to the
      incidence of proarrhythmia within these cases. SETTING: Suspected proarrhythmia
      cases were referred by cardiologists across England between 2003 and 2011.
      Information on demography, symptoms, prior medical and drug histories and data
      from hospital notes were collected. PARTICIPANTS: Two expert cardiologists
      reviewed data for 293 referred cases: 130 were included. Inclusion criteria were
      new onset or exacerbation of pre-existing ventricular arrhythmias, QTc >500 ms,
      QTc >450 ms (men) or >470 ms (women) with cardiac syncope, all secondary to drug
      administration. Exclusion criteria were acute ischaemia and ischaemic polymorphic
      ventricular tachycardia at presentation, structural heart disease, consent
      withdrawn or deceased prior to study. Descriptive analysis of Caucasian cases
      (95% of included cases, n=124) and culpable drug exposures was performed.
      RESULTS: Of the 124 Caucasian cases, 95 (77%) were QTc interval prolongation
      related; mean age was 62 years (SD 15), and 63% were female. Cardiovascular
      comorbidities included hypertension (53%) and patient-reported 'heart rhythm
      problems' (73%). Family history of sudden death (36%) and hypokalaemia at
      presentation (27%) were common. 165 culpable drug exposures were reported,
      including antiarrhythmics (42%), of which amiodarone and flecainide were the most
      common. Sotalol, a beta-blocking agent with antiarrhythmic activity, was also
      common (15%). 26% reported multiple drugs, of which 84% reported at least one
      cytochrome (CYP) P450 inhibitor. Potential pharmacodynamics interactions
      identified were mainly QT prolongation (59%). CONCLUSIONS: Antiarrhythmics, non
      cardiac drugs and drug combinations were found to be culpable in a large cohort
      of 124 clinically validated proarrhythmia cases. Potential clinical factors that
      may warn the prescriber of potential proarrhythmia include older women,
      underlying cardiovascular comorbidity, family history of sudden death and
      hypokalaemia.

PMID- 29042384
TI  - Impact of internal carotid endarterectomy on visual fields: a non-randomised
      prospective cohort study in Austria.
AB  - PURPOSE: The goal of this study was to determine whether internal carotid
      endarterectomy is associated with visual field changes. METHODS: Between March
      2007 and December 2010, a cohort study involved 29 patients with stenosis of the
      carotid artery. All patients underwent ophthalmoscopy and kinetic visual field
      examination (Goldmann perimetry) preoperatively and postoperatively. Furthermore,
      a detailed area calculation was performed. On both the operated and the
      contralateral side, the areas surrounded by the different isopters (isopter
      areas) were determined and preoperative and postoperative values compared. The
      three isopters were classified from the centre to the periphery (I, II and III).
      Isopter area values are given as ratio compared with total perimetric circle. p
      Values <0.05 were considered to be statistically significant. RESULTS: 1) The
      ophthalmologists assessment (paragraph is missing in the proof!)Eight of eleven
      patients with precarotid endarterectomy impairments experienced focal or
      concentric improvement. Six cases with preoperative concentric narrowing of the
      isopters returned to normal or improved substantially. Three out of 18 patients
      with normal preoperative visual field presented with deteriorations after
      surgery, two cases with ipsilateral and one with contralateral focal impairment.
      In 15 cases, there was no preoperative or postoperative abnormality.2) Area
      calculation (preoperative area, postoperative area, P) (paragraph is missing in
      the proof)Ipsilateral: isopter area I (0.015, 0.018, 0.131), isopter area II
      (0.107, 0.120, 0.087), isopter area III (0.392, 0.425, 0.015)Contralateral:
      isopter area I (0.017, 0.021, 0.222), isopter area II (0.119, 0.125, 0.333),
      isopter area III (0.416, 0.434, 0.171) CONCLUSIONS: We found a statistically
      significant extension of the ipsilateral peripheral isopter area (III). Further
      studies will focus on the question which subgroup is most likely to profit from
      internal carotid endarterectomy with respect to visual field changes.

PMID- 29042383
TI  - Health education for patients with acute coronary syndrome and type 2 diabetes
      mellitus: an umbrella review of systematic reviews and meta-analyses.
AB  - OBJECTIVES: This umbrella review aimed to identify the current evidence on health
      education-related interventions for patients with acute coronary syndrome (ACS)
      or type two diabetes mellitus (T2DM); identify the educational content, delivery
      methods, intensity, duration and setting required. The purpose was to provide
      recommendations for educational interventions for high-risk patients with both
      ACS and T2DM. DESIGN: Umbrella review of systematic reviews and meta-analyses.
      SETTING: Inpatient and postdischarge settings. PARTICIPANTS: Patients with ACS
      and T2DM. DATA SOURCES: CINAHL, Cochrane Library, Joanna Briggs Institute,
      Journals@Ovid, EMBase, Medline, PubMed and Web of Science databases from January
      2000 through May 2016. OUTCOMES MEASURES: Clinical outcomes (such as glycated
      haemoglobin), behavioural outcomes (such as smoking), psychosocial outcomes (such
      as anxiety) and medical service use. RESULTS: Fifty-one eligible reviews (15 for
      ACS and 36 for T2DM) consisting of 1324 relevant studies involving 2 88 057
      patients (15 papers did not provide the total sample); 30 (58.8%) reviews were
      rated as high quality. Nurses only and multidisciplinary teams were the most
      frequent professionals to provide education, and most educational interventions
      were delivered postdischarge. Face-to-face sessions were the most common delivery
      formats, and many education sessions were also delivered by telephone or via web
      contact. The frequency of educational sessions was weekly or monthly, and an
      average of 3.7 topics was covered per education session. Psychoeducational
      interventions were generally effective at reducing smoking and admissions for
      patients with ACS. Culturally appropriate health education, self-management
      educational interventions, group medical visits and psychoeducational
      interventions were generally effective for patients with T2DM. CONCLUSIONS:
      Results indicate that there is a body of current evidence about the efficacy of
      health education, its content and delivery methods for patients with ACS or T2DM.
      These results provide recommendations about the content for, and approach to,
      health education intervention for these high-risk patients.

PMID- 29042385
TI  - Association between malignancies and Marfan syndrome: a population-based, nested
      case-control study in Taiwan.
AB  - OBJECTIVE: Marfan syndrome (MFS) involves a deficiency of the structural
      extracellular matrix component fibrillin-1 and overactivation of the transforming
      growth factor-beta (TGF-beta) signalling pathway. The TGF-beta signalling pathway
      also actively participates in malignant transformation. Although anecdotal case
      reports have suggested associations between MFS/MFS-like conditions and several
      haematological and solid malignancies, such associations have not been thoroughly
      evaluated in large-scale studies. We sought to use a nationwide healthcare
      insurance claim database to evaluate whether patients with MFS are at increased
      risk of malignancy. PATIENTS AND METHODS: We conducted a nested case-control
      analysis using a database extracted from Taiwan's National Health Insurance
      Research Database. All medical conditions for each case and control were
      categorised using the International Classification of Diseases, 9th Revision
      classifications. ORs and 95% CIs for associations between MFS and malignancies
      were estimated using conditional logistic regression and adjusted for
      comorbidities. RESULTS: Our analyses included 1 153 137 cancer cases and 1 153
      137 propensity score-matched controls. Relative to other subjects, patients with
      MFS had a significantly higher risk of having a malignancy (adjusted OR 3.991)
      and hypertension (adjusted OR 1.964) and were significantly more likely to be
      men. Malignancies originating from the head and neck and the urinary tract were
      significantly more frequent among patients with MFS than among subjects without
      MFS. CONCLUSION: Patients with MFS are at increased risk of developing various
      malignancies. Healthcare professionals should be aware of this risk when treating
      such patients, and increased cancer surveillance may be necessary for these
      patients.

PMID- 29042387
TI  - Nature-based care opportunities and barriers in oncology contexts: a modified
      international e-Delphi survey.
AB  - OBJECTIVE: To develop recommendations regarding opportunities and barriers for
      nature-based care in oncology contexts using a structured knowledge generation
      process involving relevant healthcare and design experts. DESIGN: Four-round
      modified electronic Delphi study. Oncology patients' nature-based
      recommendations, uncovered in preceding qualitative investigation, were included
      in the first round for the expert participants' consideration. Key items
      (opportunities and barriers) were developed using data aggregation and synthesis,
      followed by item prioritisation and 10-point Likert scale ranking (1=not
      important, 10=very important). Descriptive statistics were calculated to assess
      items of highest importance representing expert recommendations. CONTEXT: Online
      Delphi process constituting an electronic international survey. PARTICIPANTS: A
      purposive sample of 200 potential panellists (recruitment target n=40) comprising
      healthcare practitioners, managers, designers, architects and researchers were
      invited to participate; experts were identified via research networks,
      snowballing and systematic literature review. RESULTS: 38 experts across seven
      countries (Australia, USA, UK, New Zealand, Canada, Denmark and Sweden) returned
      questionnaire 1, which determined consent and acceptance for participation.
      Initial response rate was 19%, and subsequent response rates were 84%, 82% and
      84% for rounds 2, 3 and 4, respectively. The Delphi panel developed
      recommendations consisting of 10 opportunities and 10 barriers. The following
      opportunities were rated to be of highest importance: window views from clinical
      areas onto nature; outdoor settings, gardens and courtyards with easy and
      effortless access; and nature-based physical exercise adapted to patient
      requirements. Highest-rated barriers for nature-based oncology care included lack
      of knowledge and awareness about benefits of nature engagement and
      inaccessibility, not considering access requirements for the very sick and frail.
      CONCLUSIONS: Experts suggested and agreed on a set of recommendations, which
      represent critical considerations for the safe adoption of nature-based oncology
      opportunities. These findings fill a gap in understanding about helpful nature
      based oncology care and may translate into oncology design and innovation.

PMID- 29042386
TI  - Effectiveness of an electronic patient-centred self-management tool for gout
      sufferers: a cluster randomised controlled trial protocol.
AB  - INTRODUCTION: Gout is increasing despite effective therapies to lower serum urate
      concentrations to 0.36 mmol/L or less, which, if sustained, significantly reduces
      acute attacks of gout. Adherence to urate-lowering therapy (ULT) is poor, with
      rates of less than 50% 1 year after initiation of ULT. Attempts to increase
      adherence in gout patients have been disappointing. We aim to evaluate the
      effectiveness of use of a personal, self-management, 'smartphone' application
      (app) to achieve target serum urate concentrations in people with gout. We
      hypothesise that personalised feedback of serum urate concentrations will improve
      adherence to ULT. METHODS AND ANALYSIS: Setting and designPrimary care. A
      prospective, cluster randomised (by general practitioner (GP) practices),
      controlled trial. PARTICIPANTS: GP practices will be randomised to either
      intervention or control clusters with their patients allocated to the same
      cluster. INTERVENTION: The intervention group will have access to the Healthy.me
      app tailored for the self-management of gout. The control group patients will
      have access to the same app modified to remove all functions except the Gout
      Attack Diary. PRIMARY AND SECONDARY OUTCOMES: The proportion of patients whose
      serum urate concentrations are less than or equal to 0.36 mmol/L after 6 months.
      Secondary outcomes will be proportions of patients achieving target urate
      concentrations at 12 months, ULT adherence rates, serum urate concentrations at 6
      and 12 months, rates of attacks of gout, quality of life estimations and process
      and economic evaluations. The study is designed to detect a >=30% improvement in
      the intervention group above the expected 50% achievement of target serum urate
      at 6 months in the control group: power 0.80, significance level 0.05, assumed
      'dropout' rate 20%. ETHICS AND DISSEMINATION: This study has been approved by the
      University of New South Wales Human Research Ethics Committee. Study findings
      will be disseminated in international conferences and peer-reviewed journal.
      TRIAL REGISTRATION NUMBER: ACTRN12616000455460.

PMID- 29042388
TI  - Is overseas volunteering beneficial to the NHS? The analysis of volunteers'
      responses to a feedback questionnaire following experiences in low-income and
      middle-income countries.
AB  - INTRODUCTION: Locally requested and planned overseas volunteering in low-income
      and middle-income countries by National Health Service (NHS) staff can have
      benefits for the host or receiving nation, but its impact on the professional
      development of NHS staff is not proven. The Knowledge and Skills Framework (KSF)
      and Leadership Framework (LF) are two tools used by employers as a measure of
      individuals' development. We have used dimensions from both tools as a method of
      evaluating the benefit to NHS doctors who volunteer overseas. METHODS: 88 NHS
      volunteers participating with local colleagues in Primary Trauma Care and
      orthopaedic surgical training courses in sub-Saharan Africa were asked to
      complete an online self-assessment questionnaire 6 months following their return
      to the UK. The survey consisted of questions based on qualities outlined in both
      the KSF and LF. RESULTS: 85 completed responses to the questionnaire were
      received. In every KSF domain assessed, the majority of volunteers agreed that
      their overseas volunteering experience improved their practice within the NHS.
      Self-assessed pre-course and post-course scores evaluating the LF also saw a
      universal increase, notably in the 'working with others' domain. DISCUSSION:
      There is a growing body of literature outlining the positive impact of overseas
      volunteering on NHS staff. Despite increasing evidence that such experiences can
      develop volunteers' essential skills, individuals often find it difficult to gain
      support of their employers. Our study, in line with the current literature, shows
      that overseas volunteering by NHS staff can provide an opportunity to enhance
      professional and personal development. Skills gained from volunteering within
      international links match many of the qualities outlined in both KSF and LF,
      directly contributing to volunteers' continued professional development.

PMID- 29042389
TI  - What's up doc? A national cross-sectional study of psychological wellbeing of
      hospital doctors in Ireland.
AB  - OBJECTIVES: To measure levels of psychological distress, psychological wellbeing
      and self-stigma in hospital doctors in Ireland. DESIGN: National cross-sectional
      study of randomised sample of hospital doctors. Participants provided
      sociodemographic data (age, sex, marital status), work grade (consultant,
      higher/basic specialist trainee), specialty and work hours and completed well
      being questionnaires (the Depression Anxiety Stress Scale, WHO Well-being Index,
      General Health Questionnaire) and single-item scales on self-rated health and
      self-stigma. SETTING: Irish publicly funded hospitals and residential
      institutions. PARTICIPANTS: 1749 doctors (response rate of 55%). All hospital
      specialties were represented except radiology. RESULTS: Half of participants were
      men (50.5%). Mean hours worked per week were 57 hours. Over half (52%) rated
      their health as very good/excellent, while 50.5% reported positive subjective
      well-being (WHO-5). Over a third (35%) experienced psychological distress
      (General Health Questionnaire 12). Severe/extremely severe symptoms of
      depression, anxiety and stress were evident in 7.2%, 6.1% and 9.5% of
      participants (Depression, Anxiety, Stress Scale 21). Symptoms of distress,
      depression, anxiety and stress were significantly higher and levels of well-being
      were significantly lower in trainees compared with consultants, and this was not
      accounted for by differences in sociodemographic variables. Self-stigma was
      present in 68.4%. CONCLUSIONS: The work hours of doctors working in Irish
      hospitals were in excess of European Working Time Directive's requirements. Just
      over half of hospital doctors in Ireland had positive well-being. Compared with
      international evidence, they had higher levels of psychological distress but
      slightly lower symptoms of depression and anxiety. Two-thirds of respondents
      reported self-stigma, which is likely to be a barrier to accessing care. These
      findings have implications for the design of support services for doctors, for
      discussions on quality of patient care and for future research.

PMID- 29042390
TI  - Effect of point-of-care susceptibility testing in general practice on appropriate
      prescription of antibiotics for patients with uncomplicated urinary tract
      infection: a diagnostic randomised controlled trial.
AB  - OBJECTIVES: To investigate the effect of adding point-of-care (POC)
      susceptibility testing to POC culture on appropriate use of antibiotics as well
      as clinical and microbiological cure for patients with suspected uncomplicated
      urinary tract infection (UTI) in general practice. DESIGN: Open, individually
      randomised controlled trial. SETTING: General practice. PARTICIPANTS: Women with
      suspected uncomplicated UTI, including elderly patients above 65, patients with
      recurrent UTI and patients with diabetes. The sample size calculation predicted
      600 patients were needed. INTERVENTIONS: Flexicult SSI-Urinary Kit was used for
      POC culture and susceptibility testing and ID Flexicult was used for POC culture
      only. MAIN OUTCOME MEASURES: Primary outcome: appropriate antibiotic prescribing
      on the day after consultation defined as either (1) patient with UTI: to
      prescribe a first-line antibiotic to which the infecting pathogen was susceptible
      or a second line if a first line could not be used or (2) patient without UTI:
      not to prescribe an antibiotic. UTI was defined by typical symptoms and
      significant growth in a reference urine culture performed at one of two external
      laboratories. SECONDARY OUTCOMES: clinical cure on day five according to a 7-day
      symptom diary and microbiological cure on day 14. Logistic regression models
      taking into account clustering within practices were used for analysis. RESULTS:
      20 general practices recruited 191 patients for culture and susceptibility
      testing and 172 for culture only. 63% of the patients had UTI and 12% of these
      were resistant to the most commonly used antibiotic, pivmecillinam. Patients
      randomised to culture only received significantly more appropriate treatment (OR:
      1.44 (95% CI 1.03 to 1.99), p=0.03). There was no significant difference in
      clinical or microbiological cure. CONCLUSIONS: Adding POC susceptibility testing
      to POC culture did not improve antibiotic prescribing for patients with suspected
      uncomplicated UTI in general practice. Susceptibility testing should be reserved
      for patients at high risk of resistance and complications. TRIAL REGISTRATION
      NUMBER: NCT02323087; Results.

PMID- 29042391
TI  - Korean OBEsity Surgical Treatment Study (KOBESS): protocol of a prospective
      multicentre cohort study on obese patients undergoing laparoscopic sleeve
      gastrectomy and Roux-en-Y gastric bypass.
AB  - INTRODUCTION: Bariatric surgery effectively induces long-term weight loss in
      Western populations. However, its effectiveness in Asians remains to be confirmed
      objectively. The Korean Society for Metabolic and Bariatric Surgery proposes the
      first prospective cohort study on Koreans undergoing bariatric surgery. METHODS
      AND ANALYSIS: The Korean OBEsity Surgical treatment Study (KOBESS) is a
      prospective, multicentre, single-arm, observational, cohort study on morbidly
      obese patients who undergo primary sleeve gastrectomy or Roux-en-Y gastric bypass
      in Korea. In total, 100 consecutive obese Asian patients who will undergo
      bariatric surgery will be recruited in 2016-2017; follow-up will be for 1 year.
      Primary outcomes are change in body weight and waist circumference at 1 year. All
      patients will undergo anthropometry, laboratory tests, bioelectrical impedance
      analysis, gastrofibroscopy, polysomnography and fat-measuring CT before and after
      surgery. Patients with diabetes will also undergo perioperative oral glucose
      tolerance and endocrinological hormone tests. Hypertensive patients will also
      undergo perioperative echocardiography and carotid Doppler ultrasonography.
      Female patients suspected of having polycystic ovarian syndrome will also undergo
      perioperative hormone tests and abdominal ultrasonography. Visceral and
      subcutaneous fat will be harvested during surgery. Blood, stool and urine samples
      will be taken at various perioperative time points. Although the cohort is small
      and the follow-up duration is relatively short, this study will determine whether
      bariatric surgery induces satisfactory weight loss in obese Koreans.
      Significantly, the tissue samples will also facilitate many studies examining the
      effects of bariatric surgery and their mechanisms. ETHICS AND DISSEMINATION:
      Ethics approval was obtained from the institutional review board of each
      participating hospital. All findings arising from this cohort study will be
      published in open-access peer-reviewed journals and will be presented at national
      and international meetings. All KOBESS investigators will be able to propose
      research studies and potential publications based on KOBESS data and tissue
      samples. TRIAL REGISTRATION NUMBER: NCT03100292; Pre-results.

PMID- 29042393
TI  - Effects of polyethylene glycol 2 L alone or with ascorbic acid compared with
      polyethylene glycol 4 L alone for bowel preparation before colonoscopy: protocol
      for a systematic review and network meta-analysis.
AB  - INTRODUCTION: Colonoscopy has been regarded as a standard method of detecting and
      removing gastrointestinal lesions early, while adequate bowel preparation is the
      prerequisite of determining the diagnostic accuracy and treatment safety of this
      process. Polyethylene glycol (PEG) based bowel preparation regimens remain the
      first recommendation, but the optimal option is still uncertain. The aim of this
      systematic review and network meta-analysis of randomised controlled trials
      (RCTs) is to determine the optimal PEG based bowel preparation regimen before
      colonoscopy. METHODS AND ANALYSIS: We will assign two investigators to
      independently search all potential citations, screen records, abstract essential
      information and appraise the risk of bias accordingly. Then, random effects
      pairwise and network meta-analyses of RCTs comparing PEG 2 L alone or with
      ascorbic acid with PEG 4 L alone will be performed using RevMan 5.3 (Copenhagen,
      Denmark: The Nordic Cochrane Centre, The Cochrane Collaboration, 2013), Stata 14
      (StataCorp, Texas, USA) and WinBUGS 1.4 (Imperial College School of Medicine, St
      Mary's, London, UK) from January 2000 to April 2017. The surface under the
      cumulative ranking curve will also be calculated in order to rank the regimens.
      ETHICS AND DISSEMINATION: Ethics approval and patient written informed consent
      will not be required because all of the analyses in the present study will be
      performed based on data from published studies. We will submit our systematic
      review and network meta-analysis to a peer reviewed scientific journal for
      publication. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42017068957.

PMID- 29042392
TI  - Renal and Cardiovascular Effects of sodium-glucose cotransporter 2 (SGLT2)
      inhibition in combination with loop Diuretics in diabetic patients with Chronic
      Heart Failure (RECEDE-CHF): protocol for a randomised controlled double-blind
      cross-over trial.
AB  - INTRODUCTION: Type 2 diabetes (T2D) and heart failure (HF) are a frequent
      combination, where treatment options remain limited. There has been increasing
      interest around the sodium-glucose cotransporter 2 (SGLT2) inhibitors and their
      use in patients with HF. Data on the effect of SGLT2 inhibitor use with diuretics
      are limited. We hypothesise that SGLT2 inhibition may augment the effects of loop
      diuretics and the benefits of SGLT2 inhibitors may extend beyond those of their
      metabolic (glycaemic parameters and weight loss) and haemodynamic parameters. The
      effects of SGLT2 inhibitors as an osmotic diuretic and on natriuresis may
      underlie the cardiovascular and renal benefits demonstrated in the recent EMPA
      REG study. METHODS AND ANALYSIS: To assess the effect of SGLT2 inhibitors when
      used in combination with a loop diuretic, the RECEDE-CHF (Renal and
      Cardiovascular Effects of SGLT2 inhibition in combination with loop Diuretics in
      diabetic patients with Chronic Heart Failure) trial is a single-centre,
      randomised, double-blind, placebo-controlled, cross-over trial conducted in a
      secondary care setting within NHS Tayside, Scotland. 34 eligible participants,
      aged between 18 and 80 years, with stable T2D and CHF will be recruited. Renal
      physiological testing will be performed at two points (week 1 and week 6) on each
      arm to assess the effect of 25 mg empagliflozin, on the primary and secondary
      outcomes. Participants will be enrolled in the trial for a total period between
      14 and 16 weeks. The primary outcome will assess the effect of empagliflozin
      versus placebo on urine output. The secondary outcomes are to assess the effect
      of empagliflozin on glomerular filtration rate, cystatin C, urinary sodium
      excretion, urinary protein/creatinine ratio and urinary albumin/creatinine ratio
      when compared with placebo. ETHICS AND DISSEMINATION: Ethics approval was
      obtained by the East of Scotland Research Ethics Service. Results of the trial
      will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION
      NUMBER: NCT03226457; Pre-results.

PMID- 29042394
TI  - Effects of e-learning in a continuing education context on nursing care: a review
      of systematic qualitative, quantitative and mixed studies reviews (protocol).
AB  - INTRODUCTION: Continuing education (CE) is imperative to the future of
      professional nursing. The use of e-learning by registered nurses for CE is
      spreading. A review of systematic reviews will be conducted to develop a broad
      picture of the effects of e-learning in a CE context on nursing care. METHODS AND
      ANALYSIS: Systematic qualitative, quantitative and mixed studies reviews
      published in English, French or Spanish from 1 January 2006 will be included. The
      outcomes of interest will be extracted and analysed inductively and deductively
      from the Nursing Care Performance Framework; some themes include nursing
      resources, nurses' practice environment, processes, professional satisfaction,
      and nursing sensitive outcomes. Three reviewers will independently screen first
      the title and abstract of the papers, and then the full texts in order to assess
      eligibility. Two teams of two reviewers will extract the selected reviews'
      characteristics and data. The results from various types of reviews will be
      integrated using a data-based convergent synthesis design. We will conduct a
      thematic synthesis and transform all quantitative and mixed data into qualitative
      data. ETHICS AND DISSEMINATION: Ethics approval is not required for review of
      systematic reviews. We will summarise evidence concerning the negative, neutral
      and positive effects of various forms of e-learning on different aspects of
      nursing care. If we find gaps in the literature, we will highlight them and
      suggest ideas for further research. We will also focus on positive effects and
      present, if possible, the components and characteristics of e-learning
      interventions that were found to be successful. We will present this protocol and
      results in international conferences in nursing, medical, and health informatics
      domains. We will also submit the results of our work for peer-review publication
      in a journal indexed in the international bibliographic database of biomedical
      information.

PMID- 29042395
TI  - Nuclear receptor profiling in prostatospheroids and castration-resistant prostate
      cancer.
AB  - Nuclear receptors (NRs), which belong to a superfamily of transcription factors
      and consist of a total of 48 members in humans, govern the expression of genes
      involved in a board range of developmental, reproductive, metabolic and
      immunological programs. Given the significant importance of androgen receptor and
      a few known NRs in the progression of prostate cancer, we surveyed the expression
      profiles of the entire NR superfamily in three-dimensional cultured
      prostatospheroids derived from different prostate cancer cell lines and a tumor
      xenograft model of castration-resistant prostate cancer VCaP-CRPC by quantitative
      real-time RT-PCR. Our results revealed that prostatospheroids and castration
      relapse VCaP-CRPC xenografts, both contained enriched populations of prostate
      cancer stem/progenitor-like cells (PCSCs), displayed distinct expression patterns
      of NRs. Intriguingly, most of these differentially expressed NRs were orphan NRs
      and showed upregulation. Pairwise analysis identified five orphan NRs (including
      RORbeta, TLX, COUP-TFII, NURR1 and LRH-1) that showed common upregulation in both
      mRNA and protein levels in the prostatospheroids and castration-relapse VCaP-CRPC
      xenografts, and overexpression of these orphan NRs could increase cancer stem
      cell marker expressions and enhance spheroid formation capacity in prostate
      cancer cells, suggesting that these orphan NRs might perform positive roles in
      the growth regulation of PCSCs and castration-resistant prostate cancer.
      Together, our NR expression dataset not only revealed the distinct physiologic
      status and regulatory roles governed by the networks of specific NRs but also
      some of these identified orphan NRs could be the potential therapeutic targets
      for PCSCs or castration-resistant prostate cancer.

PMID- 29042396
TI  - Differentiated thyroid cancer: millions spent with no tangible gain?
AB  - The incidence of differentiated thyroid cancer (DTC) has rapidly increased
      worldwide over the last decades. It is unknown if the increase in diagnosis has
      been mirrored by an increase in thyroidectomy rates with the concomitant economic
      impact that this would have on the health care system. DTC and thyroidectomy
      incidence as well as DTC-specific mortality were modeled using Poisson regression
      in New South Wales (NSW), Australia per year and by sex. The incidence of 2002
      was the point from which the increase in rates was assessed cumulatively over the
      subsequent decade. The economic burden of potentially avoidable thyroidectomies
      due to the increase in diagnosis was estimated as the product of the additional
      thyroidectomy procedures during a decade attributable to rates beyond those
      reported for 2002 and the national average hospital cost of an uncomplicated
      thyroidectomy in Australia. The following results were obtained. The incidence of
      both DTC and thyroidectomy doubled in NSW between 2003 and 2012, while the DTC
      specific mortality rate remained unchanged over the same period. Based on the
      2002 incidence, the projected increase over 10 years (2003-2012) in thyroidectomy
      procedures was 2196. This translates to an extra cost burden of over AUD$
      18,600,000 in surgery-related health care expenditure over one decade in NSW. Our
      findings suggest that, if this rise is solely attributable to overdetection, then
      the rising expenditure serves no additional purpose. Reducing unnecessary
      detection and a conservative approach to managing DTC are sensible and would lead
      to millions of dollars in savings and reduced harms to patients.

PMID- 29042397
TI  - Influence of Contrast Media Dose and Osmolality on the Diagnostic Performance of
      Contrast Fractional Flow Reserve.
AB  - BACKGROUND: Contrast fractional flow reserve (cFFR) is a method for assessing
      functional significance of coronary stenoses, which is more accurate than resting
      indices and does not require adenosine. However, contrast media volume and
      osmolality may affect the degree of hyperemia and therefore diagnostic
      performance. METHODS AND RESULTS: cFFR, instantaneous wave-free ratio, distal
      pressure/aortic pressure at rest, and FFR were measured in 763 patients from 12
      centers. We compared the diagnostic performance of cFFR between patients
      receiving low or iso-osmolality contrast (n=574 versus 189) and low or high
      contrast volume (n=341 versus 422) using FFR<=0.80 as a reference standard. The
      sensitivity, specificity, and overall accuracy of cFFR for the low versus iso
      osmolality groups were 73%, 93%, and 85% versus 87%, 90%, and 89%, and for the
      low versus high contrast volume groups were 69%, 99%, and 83% versus 82%, 93%,
      and 88%. By receiver operating characteristics (ROC) analysis, cFFR provided
      better diagnostic performance than resting indices regardless of contrast
      osmolality and volume (P<0.001 for all groups). There was no significant
      difference between the area under the curve of cFFR in the low- and iso
      osmolality groups (0.938 versus 0.957; P=0.40) and in the low- and high-volume
      groups (0.939 versus 0.949; P=0.61). Multivariable logistic regression analysis
      showed that neither contrast osmolality nor volume affected the overall accuracy
      of cFFR; however, both affected the sensitivity and specificity. CONCLUSIONS: The
      overall accuracy of cFFR is greater than instantaneous wave-free ratio and distal
      pressure/aortic pressure and not significantly affected by contrast volume and
      osmolality. However, contrast volume and osmolality do affect the sensitivity and
      specificity of cFFR. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov. Unique identifier: NCT02184117.

PMID- 29042399
TI  - Restenosis in a Collapsed Magnesium Bioresorbable Scaffold.

PMID- 29042398
TI  - Peripheral Artery Disease and Transcatheter Aortic Valve Replacement Outcomes: A
      Report From the Society of Thoracic Surgeons/American College of Cardiology
      Transcatheter Therapy Registry.
AB  - BACKGROUND: Peripheral artery disease (PAD) is associated with increased
      cardiovascular mortality, and PAD risk factors overlap with those for aortic
      stenosis. The prevalence and outcomes associated with PAD in a population
      undergoing transcatheter aortic valve replacement (TAVR) are unknown. METHODS AND
      RESULTS: Using the Society of Thoracic Surgeons/Transcatheter Valve Therapy
      Registry linked to Medicare claims data, we identified patients >=65 years old
      undergoing TAVR from 2011 to 2015. We calculated hazard ratios for 1-year adverse
      outcomes, including mortality, readmission, and bleeding, for patients with PAD
      compared with those without, adjusting for baseline characteristics and
      postprocedure medications. Analyses were performed separately by access site
      (transfemoral and nontransfemoral). Of 19 660 patients undergoing transfemoral
      TAVR, 4810 (24.5%) had PAD; 3730 (47.9%) of 7780 patients undergoing
      nontransfemoral TAVR had PAD. In both groups, patients with PAD were
      significantly more likely to have coronary and carotid artery diseases. At 1-year
      follow-up, patients with PAD undergoing TAVR via transfemoral access had a higher
      incidence of death (16.8% versus 14.4%; adjusted hazard ratio, 1.14; P=0.01),
      readmission (45.5% versus 42.1%; hazard ratio, 1.11; P<0.001), and bleeding
      (23.1% versus 19.7%; hazard ratio, 1.18; P<0.001) compared with patients without
      PAD. Patients with PAD undergoing TAVR via nontransfemoral access did not have
      significantly higher rates of 1-year mortality or readmission compared with
      patients without PAD. CONCLUSIONS: PAD is common among patients undergoing
      commercial TAVR via transfemoral and nontransfemoral access. Among patients
      undergoing transfemoral TAVR, PAD is associated with a higher incidence of 1-year
      adverse outcomes compared with absence of PAD. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01737528.

PMID- 29042400
TI  - Thrombus Aspiration for ST-Segment-Elevation Myocardial Infarction in Modern Era:
      Still an Issue of Debate?
AB  - The role of manual thrombus aspiration (TA) during primary percutaneous coronary
      intervention (PPCI) for acute ST-segment-elevation myocardial infarction has been
      a matter of intense research and debate now. Although recent randomized
      controlled clinical trials (notably TASTE [Thrombus Aspiration in ST-Elevation
      Myocardial Infarction in Scandinavia] and TOTAL [Trial of Routine Aspiration
      Thrombectomy With PCI Versus PCI Alone in Patients With STEMI]) do not supply
      evidence supporting the routine use of TA in patients with ST-segment-elevation
      myocardial infarction, manual TA remains a therapeutic option for interventional
      cardiologists when treating patients with substantial thrombus burden during
      PPCI. It remains unknown whether patients might actually benefit from TA applied
      in a more selective manner depending on the thrombus burden during PPCI, instead
      of routine application. In this review, we summarize current knowledge on the
      instruments used in the TA procedure, positive as well as negative clinical
      effects of TA during PPCI, and analyze the potential reasons for observed
      effects, in an effort to help the clinical decision making by physicians for the
      use of TA in individual ST-segment-elevation myocardial infarction patients
      during PPCI.

PMID- 29042401
TI  - Pulmonary Artery Denervation by Determining Targeted Ablation Sites for Treatment
      of Pulmonary Arterial Hypertension.

PMID- 29042402
TI  - Ginsenoside Rg3 ameliorated HFD-induced hepatic steatosis through downregulation
      of STAT5-PPARgamma.
AB  - Healthy expansion of adipose tissue maintains metabolic homeostasis by storing
      excess chemical energy in increased fat mass. The STAT5-PPAR gamma pathway
      reportedly regulates adipocyte differentiation, lipid metabolism and
      adipogenesis. Ginsenoside Rg3 is one of the diverse groups of steroidal saponins,
      the major active components of ginseng, which have demonstrated pharmacological
      properties. In this study, we evaluated the therapeutic effects of ginsenoside
      Rg3 under pathological conditions in vitro and in vivo We examined the effects of
      ginsenoside Rg3 on glucose level, insulin sensitivity and lipogenesis in high-fat
      diet-fed C57BL/6 mice. Ginsenoside Rg3 was also applied to the pre-adipocyte cell
      line 3T3-L1 to assess the impact on lipogenesis. Ginsenoside Rg3 reduced
      epididymal white adipose tissue (eWAT) size and hepatic steatosis, and the amount
      of triglycerides (TGs) in both eWAT and liver. Similar to the murine model, Rg3
      treated 3T3-L1 cells showed a reduction in lipid accumulation and amount of total
      TGs. Ginsenoside Rg3 regulates the expression of PPAR gamma though STAT5 in vitro
      and in vivo According to our results, lipid metabolism-related genes were
      downregulated in the high-fat mice and 3T3-L1 cell line. Rg3 shows potential for
      the amelioration of obesity-induced pathology, acting though STAT5-PPAR gamma to
      facilitate the healthy functioning of adipose tissue. This is the first report of
      evidence that obesity-induced insulin resistance and lipotoxicity can be treated
      with ginsenoside Rg3, which acts though the STAT5-PPAR gamma pathway in vivo and
      in vitro.

PMID- 29042404
TI  - Antagonistic Transcription Factor Complexes Modulate the Floral Transition in
      Rice.
AB  - Plants measure day or night lengths to coordinate specific developmental changes
      with a favorable season. In rice (Oryza sativa), the reproductive phase is
      initiated by exposure to short days when expression of HEADING DATE 3a (Hd3a) and
      RICE FLOWERING LOCUS T 1 (RFT1) is induced in leaves. The cognate proteins are
      components of the florigenic signal and move systemically through the phloem to
      reach the shoot apical meristem (SAM). In the SAM, they form a transcriptional
      activation complex with the bZIP transcription factor OsFD1 to start panicle
      development. Here, we show that Hd3a and RFT1 can form transcriptional activation
      or repression complexes also in leaves and feed back to regulate their own
      transcription. Activation complexes depend on OsFD1 to promote flowering.
      However, additional bZIPs, including Hd3a BINDING REPRESSOR FACTOR1 (HBF1) and
      HBF2, form repressor complexes that reduce Hd3a and RFT1 expression to delay
      flowering. We propose that Hd3a and RFT1 are also active locally in leaves to
      fine-tune photoperiodic flowering responses.

PMID- 29042403
TI  - Plastic Transcriptomes Stabilize Immunity to Pathogen Diversity: The Jasmonic
      Acid and Salicylic Acid Networks within the Arabidopsis/Botrytis Pathosystem.
AB  - To respond to pathogen attack, selection and associated evolution has led to the
      creation of plant immune system that are a highly effective and inducible defense
      system. Central to this system are the plant defense hormones jasmonic acid (JA)
      and salicylic acid (SA) and crosstalk between the two, which may play an
      important role in defense responses to specific pathogens or even genotypes.
      Here, we used the Arabidopsis thaliana-Botrytis cinerea pathosystem to test how
      the host's defense system functions against genetic variation in a pathogen. We
      measured defense-related phenotypes and transcriptomic responses in Arabidopsis
      wild-type Col-0 and JA- and SA-signaling mutants, coi1-1 and npr1-1, individually
      challenged with 96 diverse B. cinerea isolates. Those data showed genetic
      variation in the pathogen influences on all components within the plant defense
      system at the transcriptional level. We identified four gene coexpression
      networks and two vectors of defense variation triggered by genetic variation in
      B. cinerea This showed that the JA and SA signaling pathways functioned to
      constrain/canalize the range of virulence in the pathogen population, but the
      underlying transcriptomic response was highly plastic. These data showed that
      plants utilize major defense hormone pathways to buffer disease resistance, but
      not the metabolic or transcriptional responses to genetic variation within a
      pathogen.

PMID- 29042405
TI  - Sterol methyltransferase a target for anti-amoeba therapy: towards transition
      state analog and suicide substrate drug design.
AB  - Ergosterol biosynthesis pathways essential to pathogenic protozoa growth and
      absent from the human host offer new chokepoint targets. Here, we present
      characterization and cell-based interference of Acanthamoeba spp sterol 24-/28
      methylases (SMTs) that catalyze the committed step in C28- and C29-sterol
      synthesis. Intriguingly, our kinetic analyses suggest that 24-SMT prefers plant
      cycloartenol whereas 28-SMT prefers 24(28)-methylene lophenol in similar fashion
      to the substrate preferences of land plant SMT1 and SMT2. Transition state analog
      24(R,S),25-epiminolanosterol (EL) and suicide substrate 26,27-dehydrolanosterol
      (DHL) differentially inhibited trophozoite growth with IC50 values of 7 nM and 6
      uM, respectively, and EL yielded 20-fold higher activity than reference drug
      voriconazole. Against either SMT assayed with native substrate, EL exhibited
      tight binding ~Ki 9 nM. Alternatively, DHL is methylated at C26 by 24-SMT that
      thereby, generates intermediates that complex and inactivate the enzyme, whereas
      DHL is not productively bound to 28-SMT. Steroidal inhibitors had no effect on
      human epithelial kidney cell growth or cholesterol biosynthesis at minimum
      amoebicidal concentrations. We hypothesize the selective inhibition of
      Acanthamoeba by steroidal inhibitors representing distinct chemotypes may be an
      efficient strategy for the development of promising compounds to combat amoeba
      diseases.

PMID- 29042406
TI  - What data sources do ophthalmologists trust?
AB  - To survey ophthalmologists regarding sources they trust when incorporating new
      medical knowledge into their practice. The survey was distributed primarily to US
      based ophthalmologists. Questions were derived based on the lead author's
      research experience from congresses and discussions and from mentions in the
      medical literature. In total, 77 physicians completed the survey of 1886 sent (4%
      response rate). Regarding study design, physicians preferred a well-controlled,
      randomised, double-masked trial (99%) with multicentred investigational site
      across a wide geographical area (80%). Authorship of a research article was most
      desired from a well-known key opinion leader (KOL) (75%) or any KOL leader at a
      university (75%). The most selected journal type was a subspecialty publication
      (86%) and second a multispecialty high impact journal (77%). Study sponsorship
      was most desired from the NIH or other government agencies (71%) or a university
      (71%). Doctors preferred clinical opinions from an ophthalmic medical society
      (75%). For the source of new clinical data, physicians indicated an unsponsored
      peer-reviewed journal article (77%) or a lecture at a large ophthalmic congress
      (74%) as the preferred source. Ophthalmologists generally desire sponsors, study
      designs and opinions that appear free of bias on which to base their clinical
      practice decisions.

PMID- 29042407
TI  - Can favourable psychosocial working conditions in midlife moderate the risk of
      work exit for chronically ill workers? A 20-year follow-up of the Whitehall II
      study.
AB  - OBJECTIVES: To investigate if favourable psychosocial working conditions can
      reduce the risk of work exit and specifically for workers with chronic disease.
      METHODS: Men and women (32%) aged 35-55, working and having no chronic disease at
      baseline of the Whitehall II study of London-based civil servants were selected
      (n=9040). We observed participants' exit from work through retirement, health
      related exit and unemployment, new diagnosis of chronic disease (ie, coronary
      heart disease, diabetes, stroke and cancer) and their psychosocial working
      conditions in midlife. Using cause-specific Cox models, we examined the
      association of chronic disease and favourable psychosocial working conditions and
      their interaction, with the three types of work exit. We adjusted for gender,
      occupational grade, educational level, remaining in civil service, spouse's
      employment status and mental health. RESULTS: Chronic disease significantly
      increased the risk of any type of work exit (HR 1.27) and specifically the risk
      of health-related exit (HR 2.42). High skill discretion in midlife reduced the
      risk of any type of work exit (HR 0.90), retirement (HR 0.91) and health-related
      exit (HR 0.68). High work social support in midlife decreased the risk of health
      related exit (HR 0.79) and unemployment (HR 0.71). Favourable psychosocial
      working conditions in midlife did not attenuate the association between chronic
      disease and work exit significantly. CONCLUSIONS: The chronically ill have
      increased risks of work exit, especially through health-related exit routes.
      Chronic disease is an obstacle to extended working lives. Favourable working
      conditions directly relate to reduced risks of work exit.

PMID- 29042408
TI  - Impact of restricting diagnostic imaging reimbursement for uncomplicated low back
      pain in Ontario: a population-based interrupted time series analysis.
AB  - BACKGROUND: In 2012, the Ontario government withdrew public insurance coverage of
      imaging tests for uncomplicated low back pain. We studied the impact of this
      restriction on test ordering by physicians. METHODS: We compared the numbers of
      lumbar spine radiography, computed tomography (CT) and single-segment magnetic
      resonance imaging (MRI) studies ordered by physicians in the 3 years before and
      after the policy change. We linked claims data from the Ontario Health Insurance
      Program with physician details to calculate rates per test-ordering physician. We
      compared changes in rates of monthly test ordering by family physicians and
      specialists before and after the policy change using segmented regression
      analysis of interrupted time series data. RESULTS: The number of lumbar spine
      radiography and spine CT studies ordered by family physicians decreased by 98 597
      (28.7%) and 17 499 (28.7%), respectively, in the year after the policy change;
      there was little change in ordering by specialists. The number of lumbar spine
      radiography studies ordered per family physician by month decreased by 0.81 tests
      (p < 0.001) after the intervention, followed by a smaller rebound increase that
      remained below baseline. Monthly ordering of spine CT per family physician
      declined by 0.1 tests (p < 0.001), and that of limited spine MRI rose before the
      intervention, decreased by 0.18 tests (p < 0.001) after the intervention, then
      started to rise again. Monthly ordering of limited spine MRI by specialists,
      which had been stable before the policy change, decreased by 0.1 tests per
      specialist (p < 0.001) afterward, then rose to preintervention levels.
      INTERPRETATION: The restriction in coverage of imaging tests caused a larger
      decrease in test ordering by family physicians than by specialists and a larger,
      more sustained reduction in the use of lumbar spine radiography and spine CT than
      of spine MRI.

PMID- 29042409
TI  - RECQ-like helicases Sgs1 and BLM regulate R-loop-associated genome instability.
AB  - Sgs1, the orthologue of human Bloom's syndrome helicase BLM, is a yeast DNA
      helicase functioning in DNA replication and repair. We show that SGS1 loss
      increases R-loop accumulation and sensitizes cells to transcription-replication
      collisions. Yeast lacking SGS1 accumulate R-loops and gamma-H2A at sites of Sgs1
      binding, replication pausing regions, and long genes. The mutation signature of
      sgs1Delta reveals copy number changes flanked by repetitive regions with high R
      loop-forming potential. Analysis of BLM in Bloom's syndrome fibroblasts or by
      depletion of BLM from human cancer cells confirms a role for Sgs1/BLM in
      suppressing R-loop-associated genome instability across species. In support of a
      potential direct effect, BLM is found physically proximal to DNA:RNA hybrids in
      human cells, and can efficiently unwind R-loops in vitro. Together, our data
      describe a conserved role for Sgs1/BLM in R-loop suppression and support an
      increasingly broad view of DNA repair and replication fork stabilizing proteins
      as modulators of R-loop-mediated genome instability.

PMID- 29042412
TI  - The Use of Language in Diabetes Care and Education.
AB  - Language is powerful and can have a strong impact on perceptions as well as
      behavior. A task force, consisting of representatives from the American
      Association of Diabetes Educators (AADE) and the American Diabetes Association
      (ADA), convened to discuss language in diabetes care and education. This document
      represents the expert opinion of the task force. The literature supports the need
      for a language movement in diabetes care and education. There are effective ways
      of communicating about diabetes. This article provides recommendations for
      language used by health care professionals and others when discussing diabetes
      through spoken or written words-whether directed to people with diabetes,
      colleagues, or the general public, as well as research questions related to
      language and diabetes.

PMID- 29042411
TI  - A Horizontally Transferred Autonomous Helitron Became a Full Polydnavirus Segment
      in Cotesia vestalis.
AB  - Bracoviruses associate symbiotically with thousands of parasitoid wasp species in
      the family Braconidae, working as virulence gene vectors, and allowing the
      development of wasp larvae within hosts. These viruses are composed of multiple
      DNA circles that are packaged into infective particles, and injected together
      with wasp's eggs during parasitization. One of the viral segments of Cotesia
      vestalis bracovirus contains a gene that has been previously described as a
      helicase of unknown origin. Here, we demonstrate that this gene is a Rep/Helicase
      from an intact Helitron transposable element that covers the viral segment almost
      entirely. We also provide evidence that this element underwent at least two
      horizontal transfers, which appear to have occurred consecutively: first from a
      Drosophila host ancestor to the genome of the parasitoid wasp C. vestalis and its
      bracovirus, and then from C. vestalis to a lepidopteran host (Bombyx mori). Our
      results reinforce the idea of parasitoid wasps as frequent agents of horizontal
      transfers in eukaryotes. Additionally, this Helitron-bracovirus segment is the
      first example of a transposable element that effectively became a whole viral
      circle.

PMID- 29042410
TI  - H+ and Pi Byproducts of Glycosylation Affect Ca2+ Homeostasis and Are Retrieved
      from the Golgi Complex by Homologs of TMEM165 and XPR1.
AB  - Glycosylation reactions in the Golgi complex and the endoplasmic reticulum
      utilize nucleotide sugars as donors and produce inorganic phosphate (Pi) and acid
      (H+) as byproducts. Here we show that homologs of mammalian XPR1 and TMEM165
      (termed Erd1 and Gdt1) recycle luminal Pi and exchange luminal H+ for cytoplasmic
      Ca2+, respectively, thereby promoting growth of yeast cells in low Pi and low
      Ca2+ environments. As expected for reversible H+/Ca2+ exchangers, Gdt1 also
      promoted growth in high Ca2+ environments when the Golgi-localized V-ATPase was
      operational but had the opposite effect when the V-ATPase was eliminated. Gdt1
      activities were negatively regulated by calcineurin signaling and by Erd1, which
      recycled the Pi byproduct of glycosylation reactions and prevented the loss of
      this nutrient to the environment via exocytosis. Thus, Erd1 transports Pi in the
      opposite direction from XPR1 and other EXS family proteins and facilitates
      byproduct removal from the Golgi complex together with Gdt1.

PMID- 29042414
TI  - Mitral Valve Leaflet Remodeling After Myocardial Infarction: Good or Evil?

PMID- 29042413
TI  - Mitral Leaflet Changes Following Myocardial Infarction: Clinical Evidence for
      Maladaptive Valvular Remodeling.
AB  - BACKGROUND: Ischemic mitral regurgitation (MR) is classically ascribed to
      functional restriction of normal leaflets, but recent studies have suggested post
      myocardial infarction (MI) mitral valve (MV) leaflet fibrosis and thickening,
      challenging valve normality. Progression of leaflet thickness post-MI has not
      been studied. We hypothesized that excessive MV remodeling post-MI contributes to
      MR. Our objectives are to characterize MV changes after MI and relate them to MR.
      METHODS AND RESULTS: Three groups of 40 patients with serial echocardiograms over
      a mean of 23.4 months were identified from an echocardiography database: patients
      first studied early (6+/-12 days) and late (12+/-7 years) after an inferior MI
      and normal controls. MV thickness was correlated with MR. We studied the
      mechanisms for MV changes in a sheep model (6 apical MI versus 6 controls)
      followed for 8 weeks, with MV cellular and histopathologic analyses. Early post
      MI, leaflet thickness was found to be similar to controls (2.6+/-0.5 vs 2.5+/-0.4
      mm; P=0.23) but significantly increased over time (2.5+/-0.4 to 2.9+/-0.4 mm;
      P<0.01). In this group, patients tolerating maximal doses of renin-angiotensin
      blocking agents had less thickening (25% of patients; P<0.01). The late-MI group
      had increased thickness (3.2+/-0.5 vs 2.5+/-0.4 mm; P<0.01) without progression.
      At follow-up, 48% of post-MI patients had more than mild MR. Increased thickness
      was independently associated with MR. Experimentally, 8 weeks post-MI, MVs were 2
      fold thicker than controls, with increased collagen, profibrotic transforming
      growth factor-beta, and endothelial-to-mesenchymal transformation, confirmed by
      flow cytometry. CONCLUSIONS: MV thickness increases post-MI and correlates with
      MR, suggesting an organic component to ischemic MR. MV fibrotic remodeling can
      indicate directions for future therapy.

PMID- 29042415
TI  - Long-Term Effects of Weight Loss and Exercise on Biomarkers Associated with
      Angiogenesis.
AB  - Background: We tested the effect of weight loss on circulating levels of the
      angiogenic factors VEGF and pigment epithelium-derived factor (PEDF) in
      postmenopausal overweight/obese women, 18 months after completing a year-long 4
      arm randomized controlled trial of behavioral weight loss and/or exercise versus
      control (i.e., 30 months postrandomization).Methods: The 439 overweight/obese,
      postmenopausal women, ages 50 to 75 years, were randomized to: diet (goal: 10%
      weight loss, N = 118), exercise (225 min/wk moderate-to-vigorous activity, N =
      117), diet + exercise (N = 117), or control (N = 87). At 12 months, 399 women
      gave a blood sample; 156 returned at 30 months. Biomarkers were measured by
      immunoassay. Changes were compared using generalized estimating equations,
      adjusting for baseline BMI, age, and race/ethnicity.Results: Participants
      randomized to diet, exercise, and diet + exercise arms had greater reductions in
      VEGF at 30 months (-14.1% P = 0.02; -19.7% P = 0.003; -14.5% P = 0.002,
      respectively) versus controls (-4.5%). There were no statistically significant
      changes in PEDF in any intervention arm. Participants maintaining >=10% of
      baseline weight loss at 30 months had greater reductions in VEGF versus those who
      gained weight/had no weight change (-22.3% vs. -10.2% respectively, P = 0.002).
      Participants maintaining any weight loss had significantly lower levels of PEDF
      at 30 months versus those who gained weight/no weight change.Conclusions:
      Sustained weight loss via diet and/or exercise results in reductions in
      angiogenic factors, and can be maintained up to 30-month follow-up. Limitations
      include relatively small numbers, and possible bias toward more successful weight
      loss among women who returned at 30 months.Impact: Maintaining weight loss can
      achieve long-term reductions in biomarkers of angiogenesis that can persist up to
      18 months after completion of a weight loss intervention. Cancer Epidemiol
      Biomarkers Prev; 26(12); 1788-94. (c)2017 AACR.

PMID- 29042417
TI  - Restoration of Natural Killer Cell Antimetastatic Activity by IL12 and Checkpoint
      Blockade.
AB  - Immune checkpoint therapies target tumor antigen-specific T cells, but less is
      known about their effects on natural killer (NK) cells, which help control
      metastasis. In studying the development of lung metastases, we found that NK
      cells lose their cytotoxic capacity and acquire a molecular signature defined by
      the expression of coinhibitory receptors. In an effort to overcome this
      suppressive mechanism, we evaluated NK cell responses to the immunostimulatory
      cytokine IL12. Exposure to IL12 rescued the cytotoxicity of NK cells but also led
      to the emergence of an immature NK cell population that expressed high levels of
      the coinhibitory molecules PD-1, Lag-3, and TIGIT, thereby limiting NK cell
      mediated control of pulmonary metastases. Notably, checkpoint blockade therapy
      synergized with IL12 to fully enable tumor control by NK cells, demonstrating
      that checkpoint blockers are not only applicable to enhance T cell-mediated
      immunotherapy, but also to restore the tumor-suppressive capacity of NK cells.
      Cancer Res; 77(24); 7059-71. (c)2017 AACR.

PMID- 29042416
TI  - Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse
      Model of CIPN.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral
      nerve fiber dysfunction or degeneration, continues to be a dose-limiting and
      debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a
      taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in
      59-78% of cancer patients. Novel interventions are needed due to the current lack
      of effective CIPN treatments. Our studies were designed to investigate whether
      nicotine can prevent and/or reverse paclitaxel-induced peripheral neuropathy in a
      mouse model of CIPN, while ensuring that nicotine will not stimulate lung tumor
      cell proliferation or interfere with the antitumor properties of paclitaxel. Male
      C57BL/6J mice received paclitaxel every other day for a total of four injections
      (8 mg/kg, i.p.). Acute (0.3-0.9 mg/kg, i.p.) and chronic (24 mg/kg per day, s.c.)
      administration of nicotine respectively reversed and prevented paclitaxel-induced
      mechanical allodynia. Blockade of the antinociceptive effect of nicotine with
      mecamylamine and methyllycaconitine suggests that the reversal of paclitaxel
      induced mechanical allodynia is primarily mediated by the alpha7 nicotinic
      acetylcholine receptor subtype. Chronic nicotine treatment also prevented
      paclitaxel-induced intraepidermal nerve fiber loss. Notably, nicotine neither
      promoted proliferation of A549 and H460 non-small cell lung cancer cells nor
      interfered with paclitaxel-induced antitumor effects, including apoptosis. Most
      importantly, chronic nicotine administration did not enhance Lewis lung carcinoma
      tumor growth in C57BL/6J mice. These data suggest that the nicotinic
      acetylcholine receptor-mediated pathways may be promising drug targets for the
      prevention and treatment of CIPN.

PMID- 29042418
TI  - SOCS1 Gene Therapy Improves Radiosensitivity and Enhances Irradiation-Induced DNA
      Damage in Esophageal Squamous Cell Carcinoma.
AB  - STAT3 has been implicated recently in radioresistance in cancer. In this study,
      we investigated the association between STAT3 and radioresistance in esophageal
      squamous cell carcinoma (ESCC). Strong expression of activated phospho-STAT3 (p
      STAT3) was observed in 16/22 ESCC patients with preoperative chemoradiotherapy
      (CRT), compared with 9 of 24 patients with surgery alone, where the prognosis of
      those with CRT was poor. Expression of p-STAT3 and the antiapoptotic proteins Mcl
      1 and survivin was strongly induced in ESCC cells by irradiation. Ectopic STAT3
      expression increased radioresistance, whereas expression of the STAT3 negative
      regulator SOCS1 via an adenoviral vector improved radioresponse. Inhibiting the
      STAT3-Mcl-1 axis by SOCS1 enhanced DNA damage after irradition and induced
      apoptosis. Combining SOCS1 with radiotherapy enhanced antitumor responses in a
      murine xenograft model compared with the individual therapies. Tumor repopulation
      occurred transiently after treatment by irradiation but not the combination
      SOCS1/radiotherapy. Tumors subjected to this combination expressed high levels of
      gammaH2AX and low levels of Ki-67, which was maintained after cessation of
      treatment. Overall, we demonstrated that inhibiting the STAT3-Mcl-1 signaling
      axis by ectopic SOCS1 improved radiosensitivity by inducing apoptosis and
      enhancing DNA damage after radiotherapy, offering a mechanistic rationale for a
      new ESCC treatment. Cancer Res; 77(24); 6975-86. (c)2017 AACR.

PMID- 29042419
TI  - A 3-Month-Old With Failure to Thrive and Persistent Vomiting.
AB  - A 3-month-old boy was admitted from his pediatrician's office for failure to
      thrive and vomiting. On admission, he weighed barely more than his birth weight
      and was cachectic with muscle wasting. His abdomen was grossly distended but soft
      and nontender. A trial of nasogastric feeds resulted in a worsening of his
      clinical status. He was transferred to the ICU, and diagnostic imaging was
      concerning for a distal bowel obstruction. Surgical pathology revealed a
      surprising diagnosis, which is described in detail in the following case.

PMID- 29042420
TI  - Pulcini CD, Zima BT, Kelleher KJ, Houtrow AJ. Poverty and Trends in 3 Common
      Chronic Disorders. Pediatrics. 2017;139(3):e20162539.

PMID- 29042421
TI  - A Newborn With Abdominal Pain.
AB  - A previously healthy 3-week-old boy presented with 5 hours of marked fussiness,
      abdominal distention, and poor feeding. He was afebrile and well perfused. His
      examination was remarkable for localized abdominal tenderness and distention. He
      was referred to the emergency department in which an abdominal radiograph
      revealed gaseous distention of the bowel with a paucity of gas in the pelvis.
      Complete blood cell count and urinalysis were unremarkable. His ongoing fussiness
      and abnormal physical examination prompted consultation with surgery and
      radiology. Our combined efforts ultimately established an unexpected diagnosis.

PMID- 29042422
TI  - Cardiac Resynchronization Therapy Using Quadripolar Versus Non-Quadripolar Left
      Ventricular Leads Programmed to Biventricular Pacing With Single-Site Left
      Ventricular Pacing: Impact on Survival and Heart Failure Hospitalization.
AB  - BACKGROUND: In cardiac resynchronization therapy (CRT), quadripolar (QUAD) left
      ventricular (LV) leads are less prone to postoperative complications than non
      QUAD leads. Some studies have suggested better clinical outcomes. METHODS AND
      RESULTS: Clinical events were assessed in 847 patients after CRT-pacing or CRT
      defibrillation using either QUAD (n=287) or non-QUAD (n=560), programmed to
      single-site site LV pacing. Over a follow-up period of 3.2 years (median
      [interquartile range, 1.90-5.0]), QUAD was associated with a lower total
      mortality (adjusted hazard ratio [aHR]: 0.32, 95% confidence interval [CI], 0.20
      0.52), cardiac mortality (aHR: 0.36, 95% CI, 0.20-0.65), and heart failure (HF)
      hospitalization (aHR: 0.62, 95% CI, 0.39-0.99), after adjustment for age, sex,
      New York Heart Association class, HF etiology, device type (CRT-pacing or CRT
      defibrillation), comorbidities, atrial rhythm, medication, left ventricular
      ejection fraction, and creatinine. Death from pump failure was lower with QUAD
      (aHR: 0.33; 95% CI, 0.18-0.62), but no group differences emerged with respect to
      sudden cardiac death. There were no differences in implant-related complications.
      Re-interventions for LV displacement or phrenic nerve stimulation, which were
      lower with QUAD, predicted total mortality (aHR: 1.68, 95% CI, 1.11-2.54),
      cardiac mortality (aHR: 2.61, 95% CI, 1.66-4.11) and HF hospitalization (aHR:
      2.09, 95% CI, 1.22-3.58). CONCLUSIONS: CRT using QUAD, programmed to
      biventricular pacing with single-site LV pacing, is associated with a lower total
      mortality, cardiac mortality, and HF hospitalization. These trends were observed
      for both CRT-defibrillation and CRT-pacing, after adjustment for HF cause and
      other confounders. Re-intervention for LV lead displacement or phrenic nerve
      stimulation was associated with worse outcomes.

PMID- 29042423
TI  - Low Prevalence of Inappropriate Shocks in Patients With Inherited Arrhythmia
      Syndromes With the Subcutaneous Implantable Defibrillator Single Center
      Experience and Long-Term Follow-Up.
AB  - BACKGROUND: Up to 40% of patients with transvenous implantable cardioverter
      defibrillator (ICD) experience lead-associated complications and may suffer from
      high complication rates when lead extraction is indicated. Subcutaneous ICD may
      represent a feasible alternative; however, the efficacy of the subcutaneous ICD
      in the detection and treatment of ventricular arrhythmias in patients with
      hereditary arrhythmia syndromes has not been fully evaluated. METHODS AND
      RESULTS: Patients with primary hereditary arrhythmia syndromes who fulfilled
      indication for defibrillator placement were eligible for enrollment. Between 2010
      and 2016, 62 consecutive patients with primary hereditary arrhythmia syndromes,
      without indication for antibradycardia therapy, were enrolled in the study. Mean
      follow-up was 31.0+/-14.2 months. The study cohort comprised of 24 patients with
      Brugada syndrome, 17 with idiopathic ventricular fibrillation, 6 with long-QT
      syndrome, 1 with short-QT syndrome, 3 with catecholaminergic polymorphic
      ventricular tachycardia, 8 with hypertrophic cardiomyopathy, and 3 with
      arrhythmogenic right ventricular cardiomyopathy. Thirty-nine patients were
      implanted for secondary prevention. Twenty-two patients had a previous
      transvenous ICD implanted, but required revision because of infection or lead
      defects. A total of 20 spontaneous ventricular tachyarrhythmias requiring shock
      intervention occurred in 10 patients during follow-up. All episodes were
      terminated within the first ICD shock delivery with 80 J. Two patients had
      inappropriate therapies caused by oversensing following an uneventful
      implantation. No pocket-site infections and no premature revisions have occurred
      during follow-up. CONCLUSIONS: Our study supports the use of the subcutaneous ICD
      for both secondary and primary prevention of sudden cardiac death as a reliable
      alternative to the conventional transvenous ICD.

PMID- 29042424
TI  - Angiotensin II Receptor-Neprilysin Inhibitor Sacubitril/Valsartan Improves
      Endothelial Dysfunction in Spontaneously Hypertensive Rats.
AB  - BACKGROUND: We have previously demonstrated that antihypertensive treatment with
      renin-angiotensin system inhibitors restores the impaired endothelium-dependent
      hyperpolarization (EDH)-mediated responses in spontaneously hypertensive rats
      (SHRs). Herein, we investigated whether the angiotensin II receptor-neprilysin
      inhibitor sacubitril/valsartan (LCZ696) would improve reduced EDH-mediated
      responses and whether LCZ696 would exert additional effects on endothelium
      dependent and endothelium-independent vasorelaxation compared with an angiotensin
      II type 1 receptor blocker alone during hypertension. METHODS AND RESULTS: SHRs
      were treated for 3 months with either LCZ696 or valsartan, from the age of 8 to
      11 months. Age-matched, untreated SHRs and Wistar-Kyoto rats served as controls.
      Membrane potentials and contractile responses were recorded from the isolated
      superior mesenteric arteries. Acetylcholine-induced, EDH-mediated responses were
      impaired in untreated SHRs compared with Wistar-Kyoto rats. EDH-mediated
      responses were similarly improved in the LCZ696- and valsartan-treated SHRs. No
      difference was observed in acetylcholine-induced, nitric oxide-mediated
      relaxations among the 4 groups. Endothelium-independent relaxations in response
      to a nitric oxide donor, sodium nitroprusside, and those to levcromakalim, an ATP
      sensitive K+-channel opener, were similar among the 4 groups; however, the
      sensitivities to levcromakalim were significantly higher in both LCZ696- and
      valsartan-treated SHRs. CONCLUSIONS: LCZ696 appears to be as effective as
      valsartan in improving the impaired EDH-mediated responses during hypertension.
      LCZ696 and valsartan exert similar beneficial effects on endothelium-independent
      relaxation via enhanced sensitivity of the ATP-sensitive K+ channel. However, the
      dual blockade of renin-angiotensin system and neutral endopeptidase with LCZ696
      does not appear to provide additional benefit over valsartan alone on vasomotor
      function in mesenteric arteries of SHRs.

PMID- 29042425
TI  - Cardiovascular and Metabolic Consequences of Testosterone Supplements in Young
      and Old Male Spontaneously Hypertensive Rats: Implications for Testosterone
      Supplements in Men.
AB  - BACKGROUND: The safety of testosterone supplements in men remains unclear. In the
      present study, we tested the hypothesis that in young and old male spontaneously
      hypertensive rats (SHR), long-term testosterone supplements increase blood
      pressure and that the mechanism is mediated in part by activation of the renin
      angiotensin system. METHODS AND RESULTS: In untreated males, serum testosterone
      exhibited a sustained decrease after 5 months of age, reaching a nadir by 18 to
      22 months of age. The reductions in serum testosterone were accompanied by an
      increase in body weight until very old age (18 months). Testosterone supplements
      were given for 6 weeks to young (12 weeks-YMSHR) and old (21-22 months-OMSHR)
      male SHR that increased serum testosterone by 2-fold in young males and by 4-fold
      in old males. Testosterone supplements decreased body weight, fat mass, lean
      mass, and plasma leptin, and increased plasma estradiol in YMSHR but had no
      effect in OMSHR. Mean arterial pressure (MAP) was significantly higher in OMSHR
      than in YMSHR and testosterone supplements decreased MAP in OMSHR, but
      significantly increased MAP in YMSHR. Enalapril, the angiotensin-converting
      enzyme inhibitor, reduced MAP in both control and testosterone-supplemented
      YMSHR, but had a greater effect on MAP in testosterone-treated rats, suggesting
      the mechanism responsible for the increase in MAP in YMSHR is mediated at least
      in part by activation of the renin-angiotensin system. CONCLUSIONS: Taken
      together with previous studies, these data suggest that testosterone supplements
      may have differential effects on men depending on age, cardiovascular and
      metabolic status, and dose and whether given long-term or short-term.

PMID- 29042426
TI  - Relative Survival After Transcatheter Aortic Valve Implantation: How Do Patients
      Undergoing Transcatheter Aortic Valve Implantation Fare Relative to the General
      Population?
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is indicated for
      patients with aortic stenosis who are intermediate-high surgical risk. Although
      all-cause mortality rates after TAVI are established, survival attributable to
      the procedure is unclear because of competing causes of mortality. The aim was to
      report relative survival (RS) after TAVI, which accounts for background mortality
      risks in a matched general population. METHODS AND RESULTS: National cohort data
      (n=6420) from the 2007 to 2014 UK TAVI registry were matched by age, sex, and
      year to mortality rates for England and Wales (population, 57.9 million). The
      Ederer II method related observed patient survival to that expected from the
      matched general population. We modelled RS using a flexible parametric approach
      that modelled the log cumulative hazard using restricted cubic splines. RS of the
      TAVI cohort was 95.4%, 90.2%, and 83.8% at 30 days, 1 year, and 3 years,
      respectively. By 1-year follow-up, mortality hazards in the >85 years age group
      were not significantly different from those of the matched general population; by
      3 years, survival rates were comparable. The flexible parametric RS model
      indicated that increasing age was associated with significantly lower excess
      hazards after the procedure; for example, by 2 years, a 5-year increase in age
      was associated with 20% lower excess mortality over the general population.
      CONCLUSIONS: RS after TAVI was high, and survival rates in those aged >85 years
      approximated those of a matched general population within 3 years. High rates of
      RS indicate that patients selected for TAVI tolerate the risks of the procedure
      well.

PMID- 29042428
TI  - Sex Differential in 15-Hydroxyprostaglandin Dehydrogenase Levels in the Lumen of
      Human Intracranial Aneurysms.
AB  - BACKGROUND: Aspirin is a promising medical therapy for the prevention of
      intracranial aneurysm (IA) rupture. Recently, we found that men have a better
      response to aspirin than women. The purpose of this study was to determine
      whether a sex differential exists in the level of 15-hydroxyprostaglandin
      dehydrogenase (15-PGDH) in the lumen of human IAs. METHODS AND RESULTS:
      Consecutive patients undergoing coiling or stent-assisted coiling for a saccular
      IA at our institution were enrolled. Two samples (A and B) were collected from IA
      lumens, and the plasma level of 15-PGDH was measured using an ELISA-based method.
      The study included 38 patients, with 20 women and 18 men. Women and men were
      comparable on baseline characteristics. The mean plasma concentration of 15-PGDH
      did not differ statistically between sample A (62.8+/-16.2 ng/mL) and sample B
      (61.8+/-17.9 ng/mL; 95% confidence interval -6.6 to 9.4). The mean plasma
      concentration of 15-PGDH in IA lumens of samples A and B was significantly higher
      in men (73.8+/-13.5 ng/mL) than women (49.6+/-7.8 ng/mL; P<0.0001). CONCLUSIONS:
      Higher enzyme levels of 15-PGDH exist in the lumen of IAs of men compared with
      women. This observation could explain why aspirin confers better protection
      against IA rupture in men than in women. The susceptibility of an individual to
      aspirin may differ according to the level of 15-PGDH.

PMID- 29042427
TI  - Predictors of Death in Adults With Duchenne Muscular Dystrophy-Associated
      Cardiomyopathy.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) is frequently complicated by
      development of a cardiomyopathy. Despite significant medical advances provided to
      DMD patients over the past 2 decades, there remains a group of DMD patients who
      die prematurely. The current study sought to identify a set of prognostic factors
      that portend a worse outcome among adult DMD patients. METHODS AND RESULTS: A
      retrospective cohort of 43 consecutive patients was followed in the adult UT
      Southwestern Neuromuscular Cardiomyopathy Clinic. Clinical data were abstracted
      from the electronic medical record to generate baseline characteristics. The
      population was stratified by survival to time of analysis and compared with
      characteristics associated with death. The DMD population was in the early 20s,
      with median follow-up times over 2 years. All the patients had developed a
      cardiomyopathy, with the majority of the patients on angiotensin-converting
      enzyme inhibitors (86%) and steroids (56%), but few other guideline-directed
      heart failure medications. Comparison between the nonsurviving and surviving
      cohorts found several poor prognostic factors, including lower body mass index
      (17.3 [14.8-19.3] versus 25.8 [20.8-29.1] kg/m2, P<0.01), alanine
      aminotransferase levels (26 [18-42] versus 53 [37-81] units/L, P=0.001), maximum
      inspiratory pressures (13 [0-30] versus 33 [25-40] cmH2O, P=0.03), and elevated
      cardiac biomarkers (N-terminal pro-brain natriuretic peptide: 288 [72-1632]
      versus 35 [21-135] pg/mL, P=0.03]. CONCLUSIONS: The findings demonstrate a DMD
      population with a high burden of cardiomyopathy. The nonsurviving cohort was
      comparatively underweight, and had worse respiratory profiles and elevated
      cardiac biomarkers. Collectively, these factors highlight a high-risk
      cardiovascular population with a worse prognosis.

PMID- 29042429
TI  - Both Light Intensity and Moderate-to-Vigorous Physical Activity Measured by
      Accelerometry Are Favorably Associated With Cardiometabolic Risk Factors in Older
      Women: The Objective Physical Activity and Cardiovascular Health (OPACH) Study.
AB  - BACKGROUND: The relationship between light intensity physical activity (PA),
      which is common in older adults, and cardiovascular disease (CVD) risk factors is
      unclear. This study examined associations of accelerometer-measured PA intensity
      with CVD risk factors in older women of different race-ethnicities. METHODS AND
      RESULTS: Cross-sectional analyses were conducted in 4832 women (mean age 78.9
      years; 52.5% white, 30.5% black, 17.1% Hispanic) who were without known CVD and
      wore triaxial accelerometers a minimum of 4 of 7 days with >=10 hours/d awake
      wear-time. Vector magnitude counts per 15-s epoch were used to define time spent
      in low light (19-225 counts/15 s), high light (226-518), and moderate-to
      vigorous; >=519) intensity PA. Fasting CVD biomarkers, resting blood pressure,
      waist girth, body mass index, and 10-year predicted CVD risk (Reynolds Risk
      Score) were measured. After adjusting for age, wear time, race-ethnicity, and
      potential confounders, each PA measure was favorably associated with mean high
      density lipoprotein, triglyceride, glucose, C-reactive protein, body mass index,
      waist girth, and Reynolds Risk Score (P<0.05, all). Associations with mean blood
      pressure, insulin, and total and low-density lipoprotein cholesterol were
      variable. A 30-minute/d increment in PA was associated, on average, with odds
      ratios for high predicted CVD risk (Reynolds Risk Score >=20) of 0.96 (95%
      confidence interval, 0.92, 1.00), 0.88 (0.83, 0.94), and 0.85 (0.79, 0.91) for
      low light, high light, and moderate-to-vigorous, respectively, and remained
      significant with further mutual control for PA intensity. CONCLUSIONS: PA
      measured by accelerometry, including light intensity PA, was associated with
      lower CVD risk factor levels in race-ethnically diverse older women.

PMID- 29042431
TI  - In situ genotyping of a pooled strain library after characterizing complex
      phenotypes.
AB  - In this work, we present a proof-of-principle experiment that extends advanced
      live cell microscopy to the scale of pool-generated strain libraries. We achieve
      this by identifying the genotypes for individual cells in situ after a detailed
      characterization of the phenotype. The principle is demonstrated by single
      molecule fluorescence time-lapse imaging of Escherichia coli strains harboring
      barcoded plasmids that express a sgRNA which suppresses different genes in the E.
      coli genome through dCas9 interference. In general, the method solves the problem
      of characterizing complex dynamic phenotypes for diverse genetic libraries of
      cell strains. For example, it allows screens of how changes in regulatory or
      coding sequences impact the temporal expression, location, or function of a gene
      product, or how the altered expression of a set of genes impacts the
      intracellular dynamics of a labeled reporter.

PMID- 29042432
TI  - Special Meeting Sections for the ASM Conference on Mechanisms of Interbacterial
      Cooperation and Competition.

PMID- 29042430
TI  - Ideal Cardiovascular Health and Incident Cardiovascular Disease: Heterogeneity
      Across Event Subtypes and Mediating Effect of Blood Biomarkers: The PRIME Study.
AB  - BACKGROUND: The aim of this study was to investigate whether the association
      between baseline cardiovascular health (CVH) and incident cardiovascular disease
      differs according to coronary heart disease (CHD) and stroke subtypes, and to
      assess the mediating effect of inflammatory and hemostatic blood biomarkers.
      METHODS AND RESULTS: The association of ideal CVH with outcomes was derived in
      9312 middle-aged men from Northern Ireland and France (whole cohort) in
      multivariable Cox proportional hazards regression analysis. The mediating effect
      of baseline inflammatory and hemostatic blood biomarkers was evaluated in a case
      control study nested within the cohort after 10 years of follow-up. After a
      median follow-up of 10 years, 614 first CHD events and 117 first stroke events
      were adjudicated. Compared with those with poor CVH, those with an ideal CVH
      profile at baseline had a 72% lower risk of CHD (hazard ratio=0.28; 95%
      confidence interval, 0.17; 0.46) and a 76% lower risk of stroke (hazard ratio
      =0.24; 95% confidence interval, 0.06; 0.98). The magnitude of the risk reductions
      was similar for incident angina and myocardial infarction, but was lower for
      ischemic stroke. In the controls, the mean concentrations of high-sensitivity C
      reactive protein, IL-6, and fibrinogen decreased with higher CVH status.
      Furthermore, the association of behavioral CVH with incident CHD was partly
      mediated by high-sensitivity C-reactive protein (16.69%), IL-6 (8.52%), and
      fibrinogen (7.30%) CONCLUSIONS: Our study shows no clear heterogeneity in the
      association of baseline CVH with the main subtypes of cardiovascular disease.
      This supports a universal promotion of ideal CVH for all cardiovascular disease
      subtypes. Furthermore, our mediation analysis suggests that the lower risk of CHD
      associated with ideal CVH is partly mediated by lower inflammatory and hemostatic
      blood biomarkers.

PMID- 29042434
TI  - Trafficking of Kv2.1 Channels to the Axon Initial Segment by a Novel
      Nonconventional Secretory Pathway.
AB  - Kv2.1 is a major delayed-rectifier voltage-gated potassium channel widely
      expressed in neurons of the CNS. Kv2.1 localizes in high-density cell-surface
      clusters in the soma and proximal dendrites as well as in the axon initial
      segment (AIS). Given the crucial roles of both of these compartments in
      integrating signal input and then generating output, this localization of Kv2.1
      is ideal for regulating the overall excitability of neurons. Here we used
      fluorescence recovery after photobleaching imaging, mutagenesis, and
      pharmacological interventions to investigate the molecular mechanisms that
      control the localization of Kv2.1 in these two different membrane compartments in
      cultured rat hippocampal neurons of mixed sex. Our data uncover a unique ability
      of Kv2.1 channels to use two molecularly distinct trafficking pathways to
      accomplish this. Somatodendritic Kv2.1 channels are targeted by the conventional
      secretory pathway, whereas axonal Kv2.1 channels are targeted by a
      nonconventional trafficking pathway independent of the Golgi apparatus. We
      further identified a new AIS trafficking motif in the C-terminus of Kv2.1, and
      show that putative phosphorylation sites in this region are critical for the
      restricted and clustered localization in the AIS. These results indicate that
      neurons can regulate the expression and clustering of Kv2.1 in different membrane
      domains independently by using two distinct localization mechanisms, which would
      allow neurons to precisely control local membrane excitability.SIGNIFICANCE
      STATEMENT Our study uncovered a novel mechanism that targets the Kv2.1 voltage
      gated potassium channel to two distinct trafficking pathways and two distinct
      subcellular destinations: the somatodendritic plasma membrane and that of the
      axon initial segment. We also identified a distinct motif, including putative
      phosphorylation sites, that is important for the AIS localization. This raises
      the possibility that the destination of a channel protein can be dynamically
      regulated via changes in post-translational modification, which would impact the
      excitability of specific membrane compartments.

PMID- 29042433
TI  - Serotonin Decreases the Gain of Visual Responses in Awake Macaque V1.
AB  - Serotonin, an important neuromodulator in the brain, is implicated in affective
      and cognitive functions. However, its role even for basic cortical processes is
      controversial. For example, in the mammalian primary visual cortex (V1),
      heterogenous serotonergic modulation has been observed in anesthetized animals.
      Here, we combined extracellular single-unit recordings with iontophoresis in
      awake animals. We examined the role of serotonin on well-defined tuning
      properties (orientation, spatial frequency, contrast, and size) in V1 of two male
      macaque monkeys. We find that in the awake macaque the modulatory effect of
      serotonin is surprisingly uniform: it causes a mainly multiplicative decrease of
      the visual responses and a slight increase in the stimulus-selective response
      latency. Moreover, serotonin neither systematically changes the selectivity or
      variability of the response, nor the interneuronal correlation unexplained by the
      stimulus ("noise-correlation"). The modulation by serotonin has qualitative
      similarities with that for a decrease in stimulus contrast, but differs
      quantitatively from decreasing contrast. It can be captured by a simple additive
      change to a threshold-linear spiking nonlinearity. Together, our results show
      that serotonin is well suited to control the response gain of neurons in V1
      depending on the animal's behavioral or motivational context, complementing other
      known state-dependent gain-control mechanisms.SIGNIFICANCE STATEMENT Serotonin is
      an important neuromodulator in the brain and a major target for drugs used to
      treat psychiatric disorders. Nonetheless, surprisingly little is known about how
      it shapes information processing in sensory areas. Here we examined the
      serotonergic modulation of visual processing in the primary visual cortex of
      awake behaving macaque monkeys. We found that serotonin mainly decreased the gain
      of the visual responses, without systematically changing their selectivity,
      variability, or covariability. This identifies a simple computational function of
      serotonin for state-dependent sensory processing, depending on the animal's
      affective or motivational state.

PMID- 29042435
TI  - Autophagy induction under carbon starvation conditions is negatively regulated by
      carbon catabolite repression.
AB  - Autophagy is a conserved process in which cytoplasmic components are sequestered
      for degradation in the vacuole/lysosomes in eukaryotic cells. Autophagy is
      induced under a variety of starvation conditions, such as the depletion of
      nitrogen, carbon, phosphorus, zinc, and others. However, apart from nitrogen
      starvation, it remains unclear how these stimuli induce autophagy. In yeast, for
      example, it remains contentious whether autophagy is induced under carbon
      starvation conditions, with reports variously suggesting both induction and lack
      of induction upon depletion of carbon. We therefore undertook an analysis to
      account for these inconsistencies, concluding that autophagy is induced in
      response to abrupt carbon starvation when cells are grown with glycerol but not
      glucose as the carbon source. We found that autophagy under these conditions is
      mediated by nonselective degradation that is highly dependent on the
      autophagosome-associated scaffold proteins Atg11 and Atg17. We also found that
      the extent of carbon starvation-induced autophagy is positively correlated with
      cells' oxygen consumption rate, drawing a link between autophagy induction and
      respiratory metabolism. Further biochemical analyses indicated that maintenance
      of intracellular ATP levels is also required for carbon starvation-induced
      autophagy and that autophagy plays an important role in cell viability during
      prolonged carbon starvation. Our findings suggest that carbon starvation-induced
      autophagy is negatively regulated by carbon catabolite repression.

PMID- 29042436
TI  - Wilms tumor protein-dependent transcription of VEGF receptor 2 and hypoxia
      regulate expression of the testis-promoting gene Sox9 in murine embryonic gonads.
AB  - Wilms tumor protein 1 (WT1) has been implicated in the control of several genes
      in sexual development, but its function in gonad formation is still unclear.
      Here, we report that WT1 stimulates expression of Kdr, the gene encoding VEGF
      receptor 2, in murine embryonic gonads. We found that WT1 and KDR are co
      expressed in Sertoli cells of the testes and somatic cells of embryonic ovaries.
      Vivo-morpholino-mediated WT1 knockdown decreased Kdr transcripts in cultured
      embryonic gonads at multiple developmental stages. Furthermore, WT1 bound to the
      Kdr promoter in the chromatin of embryonic testes and ovaries. Forced expression
      of the WT1(-KTS) isoform, which functions as a transcription factor, increased
      KDR mRNA levels, whereas the WT1(+KTS) isoform, which acts presumably on the post
      transcriptional level, did not. ChIP indicated that WT1(-KTS), but not WT1(+KTS),
      binds to the KDR promoter. Treatment with the KDR tyrosine kinase inhibitor
      SU1498 or the KDR ligand VEGFA revealed that KDR signaling represses the testis
      promoting gene Sox9 in embryonic XX gonads. WT1 knockdown abrogated the
      stimulatory effect of SU1498-mediated KDR inhibition on Sox9 expression. Exposure
      to 1% O2 to mimic the low-oxygen conditions in the embryo increased Vegfa
      expression but did not affect Sox9 mRNA levels in gonadal explants. However,
      incubation in 1% O2 in the presence of SU1498 significantly reduced Sox9
      transcripts in cultured testes and increased Sox9 levels in ovaries. These
      findings demonstrate that both the local oxygen environment and WT1, which
      enhances KDR expression, contribute to sex-specific Sox9 expression in developing
      murine gonads.

PMID- 29042437
TI  - Post-translational processing and membrane translocation of the yeast regulatory
      Mid1 subunit of the Cch1/VGCC/NALCN cation channel family.
AB  - Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory
      subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation
      channel family. The amino acid sequence and voltage insensitivity of Cch1 are
      more similar to those of Na+ leak channel non-selective (NALCN) than to the
      alpha1 subunit of voltage-gated Ca2+ channels (VGCCs). Despite a lack in overall
      primary sequence similarity, Mid1 resembles in some aspects VGCC alpha2/delta
      regulatory subunits and NALCN-associated proteins. Unlike animal alpha2/delta
      subunits, Mid1 and NALCN-associated proteins are essential for the function of
      the pore-forming subunit. We herein investigated the processing and membrane
      translocation of Mid1. Mid1 was found to have a 20-amino-acid-long N-terminal
      signal peptide and appeared to be entirely localized extracellularly. A signal
      peptide-deleted Mid1 protein, Mid1DeltaN23, was N-glycosylated and retained Ca2+
      influx activity through Cch1. Moreover, an N-terminal truncation analysis
      revealed that even truncated Mid1 lacking 209 N-terminal amino acid residues was
      N-glycosylated and maintained Ca2+ influx activity. A 219-amino-acid-truncated
      Mid1 protein lost this activity but was still N-glycosylated. In the sec71Delta
      and sec72Delta single mutants defective in the post-translational protein
      transport into the endoplasmic reticulum (ER), Mid1DeltaN23 could not mediate
      Ca2+ influx and did not undergo N-glycosylation, whereas wild-type Mid1 exhibited
      normal Ca2+ influx activity and N-glycosylation in these mutants. Therefore, the
      signal peptide-lacking Mid1DeltaN23 protein may be translocated to the ER
      exclusively through the post-translational protein translocation, which typically
      requires an N-terminal signal peptide. Mid1 may provide a tool for studying
      mechanisms of protein translocation into the ER.

PMID- 29042438
TI  - The serum protein renalase reduces injury in experimental pancreatitis.
AB  - Acute pancreatitis is a disease associated with inflammation and tissue damage.
      One protein that protects against acute injury, including ischemic injury to both
      the kidney and heart, is renalase, which is secreted into the blood by the kidney
      and other tissues. However, whether renalase reduces acute injury associated with
      pancreatitis is unknown. Here, we used both in vitro and in vivo murine models of
      acute pancreatitis to study renalase's effects on this condition. In isolated
      pancreatic lobules, pretreatment with recombinant human renalase (rRNLS) blocked
      zymogen activation caused by cerulein, carbachol, and a bile acid. Renalase also
      blocked cerulein-induced cell injury and histological changes. In the in vivo
      cerulein model of pancreatitis, genetic deletion of renalase resulted in more
      severe disease, and administering rRNLS to cerulein-exposed WT mice after
      pancreatitis onset was protective. Because pathological increases in acinar cell
      cytosolic calcium levels are central to the initiation of acute pancreatitis, we
      also investigated whether rRNLS could function through its binding protein,
      plasma membrane calcium ATPase 4b (PMCA4b), which excretes calcium from cells. We
      found that PMCA4b is expressed in both murine and human acinar cells and that a
      PMCA4b-selective inhibitor worsens pancreatitis-induced injury and blocks the
      protective effects of rRNLS. These findings suggest that renalase is a protective
      plasma protein that reduces acinar cell injury through a plasma membrane calcium
      ATPase. Because exogenous rRNLS reduces the severity of acute pancreatitis, it
      has potential as a therapeutic agent.

PMID- 29042439
TI  - A genome-wide screen in Escherichia coli reveals that ubiquinone is a key
      antioxidant for metabolism of long-chain fatty acids.
AB  - Long-chain fatty acids (LCFAs) are used as a rich source of metabolic energy by
      several bacteria including important pathogens. Because LCFAs also induce
      oxidative stress, which may be detrimental to bacterial growth, it is imperative
      to understand the strategies employed by bacteria to counteract such stresses.
      Here, we performed a genetic screen in Escherichia coli on the LCFA, oleate, and
      compared our results with published genome-wide screens of multiple non
      fermentable carbon sources. This large-scale analysis revealed that among
      components of the aerobic electron transport chain (ETC), only genes involved in
      the biosynthesis of ubiquinone, an electron carrier in the ETC, are highly
      required for growth in LCFAs when compared with other carbon sources. Using
      genetic and biochemical approaches, we show that this increased requirement of
      ubiquinone is to mitigate elevated levels of reactive oxygen species generated by
      LCFA degradation. Intriguingly, we find that unlike other ETC components whose
      requirement for growth is inversely correlated with the energy yield of non
      fermentable carbon sources, the requirement of ubiquinone correlates with
      oxidative stress. Our results therefore suggest that a mechanism in addition to
      the known electron carrier function of ubiquinone is required to explain its
      antioxidant role in LCFA metabolism. Importantly, among the various oxidative
      stress combat players in E. coli, ubiquinone acts as the cell's first line of
      defense against LCFA-induced oxidative stress. Taken together, our results
      emphasize that ubiquinone is a key antioxidant during LCFA metabolism and
      therefore provides a rationale for investigating its role in LCFA-utilizing
      pathogenic bacteria.

PMID- 29042440
TI  - Plant pathogenesis-related proteins of the cacao fungal pathogen Moniliophthora
      perniciosa differ in their lipid-binding specificities.
AB  - Moniliophthora perniciosa is the causative agent of witches' broom disease, which
      devastates cacao cultures in South America. This pathogenic fungus infects
      meristematic tissues and derives nutrients from the plant apoplast during an
      unusually long-lasting biotrophic stage. To survive, the fungus produces proteins
      to suppress the plant immune response. Proteins of the PR-1 (pathogenesis-related
      1)/CAP superfamily have been implicated in fungal virulence and immune
      suppression. The genome of M. perniciosa encodes 11 homologues of plant PR-1
      proteins, designated MpPR-1 proteins, but their precise mode of action is poorly
      understood. In this study, we expressed MpPR-1 proteins in a yeast model lacking
      endogenous CAP proteins. We show that some members of the MpPR-1 family bind and
      promote secretion of sterols, whereas others bind and promote secretion of fatty
      acids. Lipid binding by purified MpPR-1 occurs with micromolar affinity and is
      saturable in vitro Sterol binding by MpPR-1 requires the presence of a flexible
      loop region containing aromatic amino acids, the caveolin-binding motif.
      Remarkably, MpPR-1 family members that do not bind sterols can be converted to
      sterol binders by a single point mutation in the caveolin-binding motif. We
      discuss the possible implications of the lipid-binding activity of MpPR-1 family
      members with regard to the mode of action of these proteins during M. perniciosa
      infections.

PMID- 29042441
TI  - Transcription factor 19 interacts with histone 3 lysine 4 trimethylation and
      controls gluconeogenesis via the nucleosome-remodeling-deacetylase complex.
AB  - Transcription factor 19 (TCF19) has been reported as a type 1 diabetes-associated
      locus involved in maintenance of pancreatic beta cells through a fine-tuned
      regulation of cell proliferation and apoptosis. TCF19 also exhibits genomic
      association with type 2 diabetes, although the precise molecular mechanism
      remains unknown. It harbors both a plant homeodomain and a forkhead-associated
      domain implicated in epigenetic recognition and gene regulation, a phenomenon
      that has remained unexplored. Here, we show that TCF19 selectively interacts with
      histone 3 lysine 4 trimethylation through its plant homeodomain finger. Knocking
      down TCF19 under high-glucose conditions affected many metabolic processes,
      including gluconeogenesis. We found that TCF19 overexpression represses de novo
      glucose production in HepG2 cells. The transcriptional repression of key genes,
      induced by TCF19, coincided with NuRD (nucleosome-remodeling-deacetylase) complex
      recruitment to the promoters of these genes. TCF19 interacted with CHD4
      (chromodomain helicase DNA-binding protein 4), which is a part of the NuRD
      complex, in a glucose concentration-independent manner. In summary, our results
      show that TCF19 interacts with an active transcription mark and recruits a co
      repressor complex to regulate gluconeogenic gene expression in HepG2 cells. Our
      study offers critical insights into the molecular mechanisms of transcriptional
      regulation of gluconeogenesis and into the roles of chromatin readers in
      metabolic homeostasis.

PMID- 29042442
TI  - 1alpha,25-Dihydroxyvitamin D3 promotes bone formation by promoting nuclear
      exclusion of the FoxO1 transcription factor in diabetic mice.
AB  - 1alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is the active form of vitamin D,
      which is responsible for reducing the risk for diabetes mellitus (DM), decreasing
      insulin resistance, and improving insulin secretion. Previous studies have shown
      that 1,25(OH)2D3 inhibited the activity of FoxO1, which has been implicated in
      the regulation of glucose metabolism. However, its function and mechanism of
      action in DM-induced energy disorders and also in bone development remains
      unclear. Here, using in vitro and in vivo approaches including osteoblast
      specific, conditional FoxO1-knock-out mice, we demonstrate that 1,25(OH)2D3
      ameliorates abnormal osteoblast proliferation in DM-induced oxidative stress
      conditions and rescues the impaired glucose and bone metabolism through FoxO1
      nuclear exclusion resulting from the activation of PI3K/Akt signaling. Using
      alizarin red staining, alkaline phosphatase assay, Western blot, and real-time
      qPCR techniques, we found that 1,25(OH)2D3 promotes osteoblast differentiation
      and expression of osteogenic phenotypic markers (i.e. alkaline phosphatase (1),
      collagen 1 (COL-1), osteocalcin (OCN), and osteopontin (OPN)) in a high-glucose
      environment. Moreover, 1,25(OH)2D3 increased both total OCN secretion and levels
      of uncarboxylated OCN (GluOC) by phosphorylating FoxO1 and promoting its nuclear
      exclusion, indicated by Western blot and cell immunofluorescence analyses. Taken
      together, our findings confirm that FoxO1 is a key mediator involved in glucose
      homeostasis and indicate that 1,25(OH)2D3 improves glucose metabolism and bone
      development via regulation of PI3K/Akt/FoxO1/OCN pathway.

PMID- 29042443
TI  - Mammalian Numb protein antagonizes Notch by controlling postendocytic trafficking
      of the Notch ligand Delta-like 4.
AB  - The biological antagonism between the signaling proteins Numb and Notch has been
      implicated in the regulation of many developmental processes, especially in
      asymmetric cell division. Mechanistic studies show that Numb inactivates Notch
      via endocytosis and proteasomal degradation that directly reduce Notch protein
      levels at the cell surface. However, some aspects of how Numb antagonizes Notch
      remain unclear. Here, we report a novel mechanism in which Numb acts as a Notch
      antagonist by controlling the intracellular destination and stability of the
      Notch ligand Delta-like 4 (Dll4) through a postendocytic-sorting process. We
      observed that Numb/Numblike knockdown increases the stability and cell-surface
      accumulation of Dll4. Further study indicated that Numb acts as a sorting switch
      to control the postendocytic trafficking of Dll4. Of note, the Numb/Numblike
      knockdown decreased Dll4 delivery to the lysosome, while increasing the recycling
      of Dll4 to the plasma membrane. Moreover, we demonstrate that this enrichment of
      Dll4 at the cell surface within Numb/Numblike knockdown cells could activate
      Notch signaling in neighboring cells. We also provide evidence that Numb
      negatively controls the Dll4 plasma membrane recycling through a well-documented
      recycling regulator protein AP1. In conclusion, our study has uncovered a
      molecular mechanism whereby Numb regulates the endocytic trafficking of the Notch
      ligand Dll4. Our findings provide a new perspective on how Numb counteracts Notch
      signaling and sheds additional critical insights into the antagonistic
      relationship between Numb and Notch signaling.

PMID- 29042444
TI  - Development of novel biosensors to study receptor-mediated activation of the G
      protein alpha subunits Gs and Golf.
AB  - Galphas (Gs) and Galphaolf (Golf) are highly homologous G-protein alpha subunits
      that activate adenylate cyclase, thereby serving as crucial mediators of
      intracellular signaling. Because of their dramatically different brain expression
      patterns, we studied similarities and differences between their activation
      processes with the aim of comparing their receptor coupling mechanisms. We
      engineered novel luciferase- and Venus-fused Galpha constructs that can be used
      in bioluminescence resonance energy transfer assays. In conjunction with
      molecular simulations, these novel biosensors were used to determine receptor
      activation-induced changes in conformation. Relative movements in Gs were
      consistent with the crystal structure of beta2 adrenergic receptor in complex
      with Gs Conformational changes in Golf activation are shown to be similar to
      those in Gs Overall the current study reveals general similarities between Gs and
      Golf activation at the molecular level and provides a novel set of tools to
      search for Gs- and Golf-specific receptor pharmacology. In view of the wide
      functional and pharmacological roles of Gs- and Golf-coupled dopamine D1 receptor
      and adenosine A2A receptor in the brain and other organs, elucidating their
      differential structure-function relationships with Gs and Golf might provide new
      approaches for the treatment of a variety of neuropsychiatric disorders. In
      particular, these novel biosensors can be used to reveal potentially therapeutic
      dopamine D1 receptor and adenosine A2A receptor ligands with functionally
      selective properties between Gs and Golf signaling.

PMID- 29042445
TI  - Analysis of substrate specificity of Trypanosoma brucei
      oligosaccharyltransferases (OSTs) by functional expression of domain-swapped
      chimeras in yeast.
AB  - N-Linked protein glycosylation is an essential and highly conserved post
      translational modification in eukaryotes. The transfer of a glycan from a lipid
      linked oligosaccharide (LLO) donor to the asparagine residue of a nascent
      polypeptide chain is catalyzed by an oligosaccharyltransferase (OST) in the lumen
      of the endoplasmic reticulum (ER). Trypanosoma brucei encodes three paralogue
      single-protein OSTs called TbSTT3A, TbSTT3B, and TbSTT3C that can functionally
      complement the Saccharomyces cerevisiae OST, making it an ideal experimental
      system to study the fundamental properties of OST activity. We characterized the
      LLO and polypeptide specificity of all three TbOST isoforms and their chimeric
      forms in the heterologous expression host S. cerevisiae where we were able to
      apply yeast genetic tools and newly developed glycoproteomics methods. We
      demonstrated that TbSTT3A accepted LLO substrates ranging from Man5GlcNAc2 to
      Man7GlcNAc2 In contrast, TbSTT3B required more complex precursors ranging from
      Man6GlcNAc2 to Glc3Man9GlcNAc2 structures, and TbSTT3C did not display any LLO
      preference. Sequence differences between the isoforms cluster in three distinct
      regions. We have swapped the individual regions between different OST proteins
      and identified region 2 to influence the specificity toward the LLO and region 1
      to influence polypeptide substrate specificity. These results provide a basis to
      further investigate the molecular mechanisms and contribution of single amino
      acids in OST interaction with its substrates.

PMID- 29042447
TI  - Anisocoria Secondary to Anticholinergic Mydriasis from Homeopathic Pink Eye
      Relief Drops.
AB  - A woman, aged 70 years, developed anisocoria after applying homeopathic eye drops
      (Similasan Pink Eye Relief) to her left eye. Her pupil was dilated for two weeks
      and did not respond to light or near stimuli for one week. Both 0.1% and 1%
      pilocarpine failed to constrict her left pupil, and magnetic resonance imaging of
      her brain did not reveal any abnormality. The eye drops she had used contain
      belladonna extracts which have a natural atropine component. This case
      demonstrates the importance, when evaluating a patient presenting with
      anisocoria, of knowing the chemical ingredients of the homeopathic eye drops,
      which often are not listed.

PMID- 29042446
TI  - Clinical and metabolic consequences of L-serine supplementation in hereditary
      sensory and autonomic neuropathy type 1C.
AB  - Hereditary sensory neuropathy type 1 (HSAN1) may be the first genetic neuropathy
      amenable to a specific mechanism-based treatment, as L-serine supplementation can
      be used to lower the neurotoxic levels of 1-deoxysphingolipids (1-deoxySL) that
      cause the neurodegeneration. The treatment is so far untested in HSAN1C caused by
      variants in the serine palmitoyl transferase subunit 2 (SPTLC2) gene. The aim of
      this study was to establish whether oral L-serine lowers 1-deoxySL in a patient
      with HSAN1C, to perform a dose escalation to find the minimal effective dose, and
      to assess the safety profile and global metabolic effects of the treatment. Our
      patient underwent a 52-wk treatment in which the L-serine dose was titrated up to
      400 mg/kg/day. She was followed up by repeated clinical examination, nerve
      conduction testing, and skin biopsies to document effects on small nerve fibers.
      Serum was assayed for 1-deoxySL and metabolomics analysis of 111 metabolites. We
      found a robust lowering of 1-deoxySL, which correlated in a near-linear fashion
      with increased serum L-serine levels. Metabolomics analysis showed a modest
      elevation in glycine and a marked reduction in the level of cytosine, whereas
      most of the other assayed metabolites did not change. There were no direct side
      effects from the treatment, but the patient developed a transitory toe ulceration
      during the course of the study. The Charcot-Marie-Tooth neuropathy score
      increased by 1 point. We conclude that oral supplementation of L-serine decreases
      1-deoxySL in HSAN1C without major global effects on metabolism. L-serine is
      therefore a potential treatment for HSAN1C.

PMID- 29042449
TI  - Peptide YY mediates the satiety effects of diets enriched with whey protein
      fractions in male rats.
AB  - Dairy proteins-whey protein, in particular-are satiating and often recommended
      for weight control; however, little is known about the mechanisms by which whey
      protein and its components promote satiety and weight loss. We used diet-induced
      obese rats to determine whether the hypophagic effects of diets that are enriched
      with whey and its fractions, lactalbumin and lactoferrin, are mediated by the gut
      hormone, peptide YY (PYY). We demonstrate that high protein diets that contain
      whey, lactalbumin, and lactoferrin decreased food intake and body weight with a
      concurrent increase in PYY mRNA abundance in the colon and/or plasma PYY
      concentrations. Of importance, blockade of PYY neuropeptide Y receptor subtype 2
      (Y2) receptors with a peripherally restricted antagonist attenuated the
      hypophagic effects of diets that are enriched with whey protein fractions. Diets
      that are enriched with whey fractions were less preferred; however, in a modified
      conditioned taste preference test, PYY Y2 receptor blockade induced hyperphagia
      of a lactoferrin diet, but caused a reduction in preference for Y2 antagonist
      paired flavor, which suggested that PYY signaling is important for lactoferrin
      induced satiety, but not essential for preference for lactoferrin-enriched diets.
      Taken together, these data provide evidence that the satiety of diets that are
      enriched with whey protein components is mediated, in part, via enhanced PYY
      secretion and action in obese male rats.-Zapata, R. C., Singh, A., Chelikani, P.
      K. Peptide YY mediates the satiety effects of diets enriched with whey protein
      fractions in male rats.

PMID- 29042448
TI  - Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled
      trials.
AB  - Myo-inositol (MI) supplementation in women with polycystic ovary syndrome (PCOS)
      has been evaluated over the last years. Many hormonal and reproductive
      impairments associated with this disorder seem relieved by the supplement. The
      objective of the meta-analysis was to assess the effects of MI alone or combined
      with d-chiro-inositol (DCI) on the endocrine and metabolic abnormalities of women
      with PCOS. Literature was retrieved from selected databases, MEDLINE, EMBASE,
      PubMed and Research Gate (up to November 2016). Only randomized controlled trials
      (RCTs) investigating the effects of MI alone or combined with DCI were reviewed.
      Nine RCTs involving 247 cases and 249 controls were included. Significant
      decreases in fasting insulin (SMD = -1.021 uU/mL, 95% CI: -1.791 to -0.251, P =
      0.009) and homeostasis model assessment (HOMA) index (SMD = -0.585, 95% CI: 
      1.145 to -0.025, P = 0.041) were identified after MI supplementation. The trial
      sequential analysis of insulin meta-analysis illustrates that the cumulative z
      curve crossed the monitoring boundary, providing firm evidence of the
      intervention effect. A slight trend toward a reduction of testosterone
      concentration by MI with respect to controls was found (SMD = -0.49, 95% CI: 
      1.072 to 0.092, P = 0.099), whereas androstenedione levels remained unaffected.
      Throughout a subgroup's meta-analysis, a significant increase in serum SHBG was
      observed only in those studies where MI was administered for at least 24 weeks
      (SMD = 0.425 nmol/L, 95% CI: 0.050-0.801, P = 0.026). These results highlight the
      beneficial effect of MI in improving the metabolic profile of women with PCOS,
      concomitantly reducing their hyperandrogenism.

PMID- 29042450
TI  - Zinc finger protein 365 is a new maternal LPS-binding protein that defends
      zebrafish embryos against gram-negative bacterial infections.
AB  - Zinc finger protein 365 (ZNF365) is widespread in animals, but its function and
      mechanism remains poorly defined. Here we clearly demonstrate that zebrafish
      ZNF365 is a newly identified LPS-binding protein capable of interacting with the
      gram-negative bacteria Escherichia coli, Vibrio anguillarum, and Aeromonas
      hydrophila, and functions as an antibacterial effector molecule capable of
      directly killing the bacteria. We also reveal that N-terminal residues 30-55
      consisting of the ZnF_C2H2 domain are indispensable for ZNF365 antimicrobial
      activity. Importantly, microinjection of recombinant ZNF365 into early embryos
      significantly enhanced the resistance of the embryos against pathogenic A.
      hydrophila challenge, whereas down-regulation of ZNF365 by injection of znf365
      morpholino into embryos considerably lowered their resistance against A.
      hydrophila challenge. Furthermore, the N-terminal peptide Z30-55 with in vitro
      antibacterial activity also promoted the resistance of embryos against A.
      hydrophila, but the peptide Z56-345 without in vitro antibacterial activity did
      not. Collectively, these results indicate that ZNF365 is a maternal LPS-binding
      protein that can protect the early embryos of zebrafish against pathogenic
      attacks, a novel role to be assigned to ZNF365 proteins. This work also provides
      new insights into the immunologic function of the zinc finger proteins that are
      widely distributed in various animals.-Du, X., Zhou, Y., Song, L., Wang, X.,
      Zhang, S. Zinc finger protein 365 is a new maternal LPS-binding protein that
      defends zebrafish embryos against gram-negative bacterial infections.

PMID- 29042452
TI  - Export of membrane proteins from the Golgi complex to the primary cilium requires
      the kinesin motor, KIFC1.
AB  - Microtubule-based motors contribute to the efficiency and selectivity of Golgi
      exit and post-Golgi transport of membrane proteins that are targeted to distinct
      compartments. Cytoplasmic dynein moves post-Golgi vesicles that carry rhodopsin
      toward the base of the connecting cilium in photoreceptor cells; however, the
      identity of the motors that are involved in the vesicular trafficking of ciliary
      membrane proteins in nonphotoreceptor cells remains unclear. Here, we demonstrate
      that the minus end-directed kinesin KIFC1 (kinesin family member C1) is required
      for both ciliary membrane protein transport and serum starvation-induced
      ciliogenesis in retinal pigmented epithelial 1 cells. Although KIFC1 is known as
      a mitotic motor that is sequestered in the nucleus during interphase, KIFC1
      immunoreactivity appeared in the Golgi region after serum starvation. Knockdown
      of KIFC1 inhibited the export of ciliary receptors from the Golgi complex. KIFC1
      overexpression affected the Golgi localization of GMAP210 (Golgi microtubule
      associated protein 210) and IFT20 (intraflagellar transport 20), which are
      involved in membrane protein transport to cilia. Moreover, KIFC1 physically
      interacted with ASAP1 (ADP-ribosylation factor GTPase-activating protein with SH3
      domain, ankyrin repeat and PH domain 1), which regulates the budding of rhodopsin
      transport carriers from the Golgi complex, and KIFC1 depletion caused Golgi
      accumulation of ASAP1. A decrease in the centrosomal levels of IFT20 and TTBK2
      (tau-tubulin kinase 2) was associated with ciliogenesis defects in KIFC1-depleted
      cells. Our results suggest that KIFC1 plays roles in the Golgi exit of ciliary
      receptors and in the recruitment of ciliogenesis regulators.-Lee, S.-H., Joo, K.,
      Jung, E. J., Hong, H., Seo, J., Kim, J. Export of membrane proteins from the
      Golgi complex to the primary cilium requires the kinesin motor, KIFC1.

PMID- 29042451
TI  - Biased signaling of the proton-sensing receptor OGR1 by benzodiazepines.
AB  - GPCRs have diverse signaling capabilities, based on their ability to assume
      various conformations. Moreover, it is now appreciated that certain ligands can
      promote distinct receptor conformations and thereby bias signaling toward a
      specific pathway to differentially affect cell function. The recently
      deorphanized G protein-coupled receptor OGR1 [ovarian cancer G protein-coupled
      receptor 1 ( GPR68)] exhibits diverse signaling events when stimulated by
      reductions in extracellular pH. We recently demonstrated airway smooth muscle
      cells transduce multiple signaling events, reflecting a diverse capacity to
      couple to multiple G proteins. Moreover, we recently discovered that the
      benzodiazepine lorazepam, more commonly recognized as an agonist of the gamma
      aminobutyric acid A (GABAA) receptor, can function as an allosteric modulator of
      OGR1 and, similarly, can promote multiple signaling events. In this study, we
      demonstrated that different benzodiazepines exhibit a range of biases for OGR1,
      with sulazepam selectively activating the canonical Gs of the G protein signaling
      pathway, in heterologous expression systems, as well as in several primary cell
      types. These findings highlight the potential power of biased ligand pharmacology
      for manipulating receptor signaling qualitatively, to preferentially activate
      pathways that are therapeutically beneficial.-Pera, T., Deshpande, D. A.,
      Ippolito, M., Wang, B., Gavrila, A., Michael, J. V., Nayak, A. P., Tompkins, E.,
      Farrell, E., Kroeze, W. K., Roth, B. L., Panettieri, R. A. Jr Benovic, J. L., An,
      S. S., Dulin, N. O., Penn, R. B. Biased signaling of the proton-sensing receptor
      OGR1 by benzodiazepines.

PMID- 29042453
TI  - Bisphenol A promotes hyperuricemia via activating xanthine oxidase.
AB  - The prevalence of hyperuricemia has increased rapidly over the past decades.
      Bisphenol A (BPA) is an environmental endocrine disruptor. We investigated the
      effects of BPA on uric acid metabolism and its potential mechanisms. Experiments
      were performed in different animal models, cell cultures, and humans. In 3
      different animal models, BPA exposure increased serum and hepatic uric acid with
      enhanced activity of xanthine oxidase (XO) in liver, whereas the excretion of
      uric acid was unchanged. Both in vivo and in vitro, BPA-induced uric acid
      production was decreased after treatment with allopurinol, which is a XO
      inhibitor. XO led to the accumulation of uric acid after xanthine was added, with
      the enzyme-catalyzed reaction, which was enhanced by BPA. Altered secondary
      structures of XO were found by circular dichroism analysis in the conditions of
      different BPA concentrations. Molecular docking portrayed Asp360 and Lys422 of XO
      to be the preferred binding sites for BPA. Mutation of both sites significantly
      blocked the effect of BPA on XO activity. In humans, patients with hyperuricemia
      exhibited higher levels of serum BPA than subjects without hyperuricemia. These
      findings demonstrate BPA promotes hyperuricemia by increasing hepatic uric acid
      synthesis via the activation of XO, probably through direct binding.-Ma, L., Hu,
      J., Li, J., Yang, Y., Zhang, L., Zou, L., Gao, R., Peng, C., Wang, Y., Luo, T.,
      Xiang, X., Qing, H., Xiao, X., Wu, C., Wang, Z., He, J. C., Li, Q., Yang, S.
      Bisphenol A promotes hyperuricemia via activating xanthine oxidase.

PMID- 29042454
TI  - Complement-Activating Anti-HLA Antibodies in Kidney Transplantation: Allograft
      Gene Expression Profiling and Response to Treatment.
AB  - Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated
      with impaired kidney transplant outcome; however, whether these antibodies induce
      a specific rejection phenotype and influence response to therapy remains
      undetermined. We prospectively screened 931 kidney recipients for complement
      activating DSAs and used histopathology, immunostaining, and allograft gene
      expression to assess rejection phenotypes. Effector cells were evaluated using in
      vitro human cell cultures. Additionally, we assessed the effect of complement
      inhibition on kidney allograft rejection phenotype and the clinical response to
      complement inhibition in 116 independent kidney recipients with DSAs at
      transplant receiving rejection prophylaxis with eculizumab or standard of care
      (plasma exchange and intravenous Ig) at ten international centers. The
      histomolecular rejection phenotype associated with complement-activating DSA was
      characterized by complement deposition and accumulation of natural killer cells
      and monocytes/macrophages in capillaries and increased expression of five
      biologically relevant genes (CXCL11, CCL4, MS4A7, MS4A6A, and FCGR3A) indicative
      of endothelial activation, IFNgamma response, CD16-mediated natural killer cell
      activation, and monocyte/macrophage activation. Compared with standard of care,
      eculizumab specifically abrogated this histomolecular rejection phenotype and
      associated with a decreased 3-month rejection incidence rate in patients with
      complement-activating DSAs (56%; 95% confidence interval [95% CI], 38% to 74%
      versus 19%; 95% CI, 8% to 35%; P=0.001) but not in those with noncomplement
      activating DSAs (9%; 95% CI, 2% to 25% versus 13%; 95% CI, 2% to 40%; P=0.65). In
      conclusion, circulating complement-activating anti-HLA DSAs are associated with a
      specific histomolecular kidney allograft rejection phenotype that can be
      abrogated by complement inhibition.

PMID- 29042455
TI  - MicroRNA-709 Mediates Acute Tubular Injury through Effects on Mitochondrial
      Function.
AB  - Mitochondrial dysfunction has important roles in the pathogenesis of AKI, yet
      therapeutic approaches to improve mitochondrial function remain limited. In this
      study, we investigated the pathogenic role of microRNA-709 (miR-709) in mediating
      mitochondrial impairment and tubular cell death in AKI. In a cisplatin-induced
      AKI mouse model and in biopsy samples of human AKI kidney tissue, miR-709 was
      significantly upregulated in the proximal tubular cells (PTCs). The expression of
      miR-709 in the renal PTCs of patients with AKI correlated with the severity of
      kidney injury. In cultured mouse PTCs, overexpression of miR-709 markedly induced
      mitochondrial dysfunction and cell apoptosis, and inhibition of miR-709
      ameliorated cisplatin-induced mitochondrial dysfunction and cell injury. Further
      analyses showed that mitochondrial transcriptional factor A (TFAM) is a target
      gene of miR-709, and genetic restoration of TFAM attenuated mitochondrial
      dysfunction and cell injury induced by cisplatin or miR-709 overexpression in
      vitro Moreover, antagonizing miR-709 with an miR-709 antagomir dramatically
      attenuated cisplatin-induced kidney injury and mitochondrial dysfunction in mice.
      Collectively, our results suggest that miR-709 has an important role in mediating
      cisplatin-induced AKI via negative regulation of TFAM and subsequent
      mitochondrial dysfunction. These findings reveal a pathogenic role of miR-709 in
      acute tubular injury and suggest a novel target for the treatment of AKI.

PMID- 29042456
TI  - Effects of Two Immunosuppressive Treatment Protocols for IgA Nephropathy.
AB  - The role of immunosuppression in IgA nephropathy (IgAN) is controversial. In the
      Supportive Versus Immunosuppressive Therapy for the Treatment of Progressive IgA
      Nephropathy (STOP-IgAN) Trial, 162 patients with IgAN and proteinuria >0.75 g/d
      after 6 months of optimized supportive care were randomized into two groups:
      continued supportive care or additional immunosuppression (GFR>=60 ml/min per
      1.73 m2: 6-month corticosteroid monotherapy; GFR=30-59 ml/min per 1.73 m2:
      cyclophosphamide for 3 months followed by azathioprine plus oral prednisolone).
      Coprimary end points were full clinical remission and GFR loss >=15 ml/min per
      1.73 m2 during the 3-year trial phase. In this secondary intention to treat
      analysis, we separately analyzed data from each immunosuppression subgroup and
      the corresponding patients on supportive care. Full clinical remission occurred
      in 11 (20%) patients receiving corticosteroid monotherapy and three (6%) patients
      on supportive care (odds ratio, 5.31; 95% confidence interval, 1.07 to 26.36;
      P=0.02), but the rate did not differ between patients receiving immunosuppressive
      combination and controls on supportive care (11% versus 4%, respectively;
      P=0.30). The end point of GFR loss >=15 ml/min per 1.73 m2 did not differ between
      groups. Only corticosteroid monotherapy transiently reduced proteinuria at 12
      months. Severe infections, impaired glucose tolerance, and/or weight gain in the
      first year were more frequent with either immunosuppressive regimen than with
      supportive care. In conclusion, only corticosteroid monotherapy induced disease
      remission in a minority of patients who had IgAN with relatively well preserved
      GFR and persistent proteinuria. Neither immunosuppressive regimen prevented GFR
      loss, and both associated with substantial adverse events.

PMID- 29042457
TI  - Neutralizing Antibody-Mediated Response and Risk of BK Virus-Associated
      Nephropathy.
AB  - BK virus-associated nephropathy (BKVAN) causes renal allograft dysfunction. The
      current management of BKVAN relies on pre-emptive adaptation of immunosuppression
      according to viral load monitoring. However, this empiric strategy is not always
      successful. Therefore, pretransplant predictive markers are needed. In a
      prospective longitudinal study, we enrolled 168 kidney transplant recipients and
      69 matched donors. To assess the value of BKV genotype-specific neutralizing
      antibody (NAb) titers as a predictive marker for BKV replication, we measured BKV
      DNA load and NAb titers at transplant and followed patients for 24 months. After
      transplant, 52 (31%) patients displayed BKV replication: 24 (46%) patients were
      viruric and 28 (54%) patients were viremic, including 13 with biopsy-confirmed
      BKVAN. At any time, patients with high NAb titers against the replicating strain
      had a lower risk of developing BKV viremia (hazard ratio [HR], 0.44; 95%
      confidence interval [95% CI], 0.26 to 0.73; P=0.002). Each log10 increase in NAb
      titer decreased the risk of developing viremia by 56%. Replicating strains were
      consistent with donor transmission in 95% of cases of early BKV replication.
      Genotype mismatch between recipients' neutralization profiles before transplant
      and their subsequently replicating strain significantly increased the risk of
      developing viremia (HR, 2.27; 95% CI, 1.06 to 4.88; P=0.04). A NAb titer against
      the donor's strain <4 log10 before transplant significantly associated with BKV
      replication after transplant (HR, 1.88; 95% CI, 1.06 to 3.45; P=0.03). BKV
      genotype-specific NAb titers may be a meaningful predictive marker that allows
      patient stratification by BKV disease risk before and after transplant.

PMID- 29042458
TI  - Exenatide modulates tumor-endothelial cell interactions in human ovarian cancer
      cells.
AB  - Diabetes and cancer are prevalent diseases whose incidence is increasing
      globally. Diabetic women have a moderate risk increase in ovarian cancer,
      suggested to be due to an interaction between these two disorders. Furthermore,
      patients manifesting both diseases have associated worse prognosis, reduced
      survival and shorter relapse-free survival. According to current recommendations,
      incretin drugs such as Exenatide, a synthetic analog of Exendin-4, and
      Liraglutide are used as therapy for the type 2 diabetes (T2D). We studied the
      effects of GLP-1 and Exendin-4 on migration, apoptosis and metalloproteinase
      production in two human ovarian cancer cells (SKOV-3 and CAOV-3). Exendin-4
      inhibited migration and promoted apoptosis through caspase 3/7 activation.
      Exendin-4 also modulated the expression of key metalloproteinases (MMP-2 and MMP
      9) and their inhibitors (TIMP-1 and TIMP-2). Vascular endothelial cells, which
      contribute to the formation and progression of metastasis, were also analyzed.
      TNF-alpha-stimulated endothelial cells from iliac artery after Exendin-4
      treatment showed reduced production of adhesion molecules (ICAM-1 and VCAM-1).
      Additionally, incretin treatment inhibited activation of apoptosis in TNF-alpha
      stimulated endothelial cells. In the same experiment, MMPs (MMP-1 and MMP-9),
      which are relevant for tumor development, were also reduced. Our study
      demonstrated that incretin drugs may reduce cancer cell proliferation and
      dissemination potential, hence limiting the risk of metastasis in epithelial
      ovarian cancer.

PMID- 29042460
TI  - Storage Compartments for Capillary Water Rarely Refill in an Intact Woody Plant.
AB  - Water storage is thought to play an integral role in the maintenance of whole
      plant water balance. The contribution of both living and dead cells to water
      storage can be derived from rehydration and water-release curves on excised plant
      material, but the underlying tissue-specific emptying/refilling dynamics remain
      unclear. Here, we used x-ray computed microtomography to characterize the
      refilling of xylem fibers, pith cells, and vessels under both excised and in vivo
      conditions in Laurus nobilis In excised stems supplied with water, water uptake
      exhibited a biphasic response curve, and x-ray computed microtomography images
      showed that high water storage capacitance was associated with fiber and pith
      refilling as driven by capillary forces: fibers refilled more rapidly than pith
      cells, while vessel refilling was minimal. In excised stems that were sealed,
      fiber and pith refilling was associated with vessel emptying, indicating a link
      between tissue connectivity and water storage. In contrast, refilling of fibers,
      pith cells, and vessels was negligible in intact saplings over two time scales,
      24 h and 3 weeks. However, those compartments did refill slowly when the shoot
      was covered to prevent transpiration. Collectively, our data (1) provide direct
      evidence that storage compartments for capillary water refill in excised stems
      but rarely under in vivo conditions, (2) highlight that estimates of capacitance
      from excised samples should be interpreted with caution, as certain storage
      compartments may not be utilized in the intact plant, and (3) question the
      paradigm that fibers play a substantial role in daily discharge/recharge of stem
      capacitance in an intact tree.

PMID- 29042461
TI  - How do we improve training in pulmonary physiology and the interpretation of lung
      function tests?

PMID- 29042459
TI  - Environmental and Genetic Factors Regulating Localization of the Plant Plasma
      Membrane H+-ATPase.
AB  - A P-type H+-ATPase is the primary transporter that converts ATP to
      electrochemical energy at the plasma membrane of higher plants. Its product, the
      proton-motive force, is composed of an electrical potential and a pH gradient.
      Many studies have demonstrated that this proton-motive force not only drives the
      secondary transporters required for nutrient uptake, but also plays a direct role
      in regulating cell expansion. Here, we have generated a transgenic Arabidopsis
      (Arabidopsis thaliana) plant expressing H+-ATPase isoform 2 (AHA2) that is
      translationally fused with a fluorescent protein and examined its cellular
      localization by live-cell microscopy. Using a 3D imaging approach with seedlings
      grown for various times under a variety of light intensities, we demonstrate that
      AHA2 localization at the plasma membrane of root cells requires light. In dim
      light conditions, AHA2 is found in intracellular compartments, in addition to the
      plasma membrane. This localization profile was age-dependent and specific to cell
      types found in the transition zone located between the meristem and elongation
      zones. The accumulation of AHA2 in intracellular compartments is consistent with
      reduced H+ secretion near the transition zone and the suppression of root growth.
      By examining AHA2 localization in a knockout mutant of a receptor protein kinase,
      FERONIA, we found that the intracellular accumulation of AHA2 in the transition
      zone is dependent on a functional FERONIA-dependent inhibitory response in root
      elongation. Overall, this study provides a molecular underpinning for
      understanding the genetic, environmental, and developmental factors influencing
      root growth via localization of the plasma membrane H+-ATPase.

PMID- 29042463
TI  - Need to Reclassify Etiologies of ESRD on the CMS 2728 Medical Evidence Report.

PMID- 29042462
TI  - Infrequent Provision of Palliative Care to Patients with Dialysis-Requiring AKI.
AB  - BACKGROUND AND OBJECTIVES: The use of palliative care in AKI is not well
      described. We sought to better understand palliative care practice patterns for
      hospitalized patients with AKI requiring dialysis in the United States. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: Using the 2012 National Inpatient Sample,
      we identified patients with AKI and palliative care encounters using validated
      International Classification of Diseases, Ninth Revision, Clinical Modification
      codes. We compared palliative care encounters in patients with AKI requiring
      dialysis, patients with AKI not requiring dialysis, and patients without AKI. We
      described the provision of palliative care in patients with AKI requiring
      dialysis and compared the frequency of palliative care encounters for patients
      with AKI requiring dialysis with that for patients with other illnesses with
      similarly poor prognoses. We used logistic regression to determine factors
      associated with the provision of palliative care, adjusting for demographics,
      hospital-level variables, and patient comorbidities. RESULTS: We identified
      3,031,036 patients with AKI, of whom 91,850 (3%) received dialysis. We observed
      significant patient- and hospital-level differences in the provision of
      palliative care for patients with AKI requiring dialysis; adjusted odds were 26%
      (95% confidence interval, 12% to 38%) lower in blacks and 23% (95% confidence
      interval, 3% to 39%) lower in Hispanics relative to whites. Lower provision of
      palliative care was observed for rural and urban nonteaching hospitals relative
      to urban teaching hospitals, small and medium hospitals relative to large
      hospitals, and hospitals in the Northeast compared with the South. After
      adjusting for age and sex, there was low utilization of palliative care services
      for patients with AKI requiring dialysis (8%)-comparable with rates of
      utilization by patients with other illnesses with poor prognosis, including
      cardiogenic shock (9%), intracranial hemorrhage (10%), and acute respiratory
      distress syndrome (10%). CONCLUSIONS: The provision of palliative care varied
      widely by patient and facility characteristics. Palliative care was infrequently
      used in hospitalized patients with AKI requiring dialysis, despite its poor
      prognosis and the regular application of life-sustaining therapy.

PMID- 29042464
TI  - Recognizing the Elephant in the Room: Palliative Care Needs in Acute Kidney
      Injury.

PMID- 29042466
TI  - Survey of Radioactive Items in the Home.
AB  - Whether it be from the sun or naturally encountered substances, we are exposed to
      radiation every day. Some items found in the home either are naturally
      radioactive or have a component containing radioactive material. This study was
      conducted to assess exposure from 4 such items previously shown to be
      radioactive: Fiestaware, granite, smoke detectors, and Brazil nuts. Using 3 types
      of radiation detectors to obtain quantitative and qualitative information on the
      radioactive properties of these items, we found little to no harmful radiation
      exposure from any of them.

PMID- 29042465
TI  - Thrombotic Microangiopathy and the Kidney.
AB  - Thrombotic microangiopathy can manifest in a diverse range of diseases and is
      characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ
      injury, including AKI. It can be associated with significant morbidity and
      mortality, but a systematic approach to investigation and prompt initiation of
      supportive management and, in some cases, effective specific treatment can result
      in good outcomes. This review considers the classification, pathology,
      epidemiology, characteristics, and pathogenesis of the thrombotic
      microangiopathies, and outlines a pragmatic approach to diagnosis and management.

PMID- 29042467
TI  - Variability in Heart-to-Mediastinum Ratio from Planar 123I-MIBG Images of a
      Thorax Phantom for 6 Common gamma-Camera Models.
AB  - A heart-to-mediastinum (H/M) ratio of 1.6 or greater on planar 123I-iobenguane
      (123I-MIBG) images identifies heart failure patients at low risk of experiencing
      an adverse cardiac event. This phase-4 study used standardized phantoms to assess
      the intercamera, intracamera, and interhead variability in H/M ratio
      determinations from planar cardiac 123I-MIBG imaging using commercially
      available, dual-head gamma-cameras. Methods: A fillable thorax phantom was
      developed to simulate the typical uptake of 123I-MIBG. The phantom had a nominal
      H/M ratio of 1.6 on the reference camera. Commercial cameras used in the study
      were dual-head and capable of 90 degrees  configuration for cardiac imaging. The
      target sample size was 8 units (examples) per camera model. Two imaging
      technologists independently analyzed planar images of simulated 123I-MIBG uptake
      from the thorax phantom. H/M was the ratio of the average counts per pixel of the
      heart and mediastinum regions of interest. The primary endpoint, intercamera
      variability in H/M ratio from head 1, was determined for each camera model via
      comparison with the H/M ratio on the reference camera. Only cameras with at least
      8 units tested (n >= 8) were included in the primary analysis. Intracamera and
      interhead variability in the H/M ratio were also evaluated. Results: Nine camera
      models were studied. The mean H/M ratio ranged from 1.342 to 1.677. The primary
      analysis (6 camera models) using a mixed-model, repeated-measures analysis showed
      no significant difference in H/M ratio between any camera model and the reference
      camera. Intracamera variability (head 1) in the H/M ratio among camera models
      with 8 units or more was high, with SDs ranging from 0.0455 to 0.1193. Interhead
      variability was low (SDs of the interhead difference, 0.017-0.074). Conclusion:
      Commonly used gamma-cameras produced H/M ratios from simulated 123I-MIBG phantom
      images that were not significantly different from those on the reference camera.
      This finding indicates that the results of previous clinical trials of 123I-MIBG,
      involving many different clinical sites and camera models, are valid. The
      assessment of the performance of a given camera unit using an 123I planar phantom
      before H/M results from 123I-MIBG imaging are used for classifying risk in heart
      failure patients is encouraged.

PMID- 29042468
TI  - Comparison of Step-and-Shoot and Continuous-Bed-Motion PET Modes of Acquisition
      for Limited-View Organ Scans.
AB  - Continuous-bed-motion (CBM) acquisition mode has been made commercially available
      in PET/CT scanners. CBM mode is designed for whole-body imaging, with a long scan
      length (multiple axial fields of view [aFOVs]) and short acquisition duration (2
      3 min/aFOV). PET/CT has recently been used after 90Y-microsphere therapy to
      quantify 90Y activity distribution in the liver. Here we compared counting
      efficiencies along the bed-motion direction (z-axis) between CBM and step-and
      shoot (SS) acquisition modes for limited-view organ scans, such as 90Y PET/CT
      liver studies, that have short scan lengths (<=2 aFOVs) and long acquisition
      durations (10-30 min/aFOV). Methods: The counting efficiencies, that is, analytic
      sensitivities, in SS mode (single-aFOV and multiple-aFOV scans) and CBM mode were
      theoretically derived and experimentally validated using a cylindric 68Ge
      phantom. The sensitivities along the z-axis were compared between the SS and CBM
      modes. Results: The analytic and experimental count profiles were in good
      agreement, validating the analytic models. For fixed scan durations, the overall
      coincidence counting efficiency in CBM mode was lower (~60%) than those in SS
      modes, and the maximum sensitivity in CBM mode was 50% or less of that in 1-aFOV
      SS mode and 100% or less of that in 2-aFOV SS mode. Conclusion: The ability of
      CBM mode to tailor-fit the PET/CT scan length and local scan duration is not
      realized in studies with a short scan length (<=30 cm) and long scan duration (20
      min/aFOV for the scanner). SS acquisition mode is preferable to CBM mode for
      limited-view organ and count-starved scans, such as 90Y PET/CT liver scans,
      because of the higher counting efficiency of SS mode, which leads to better image
      quality and quantification precision.

PMID- 29042469
TI  - The Importance of Quality Control for Clinical PET Imaging.

PMID- 29042470
TI  - Comparison Between Prone and Upright Imaging of the Inferior Wall Using 201TlCl
      Myocardial Perfusion SPECT.
AB  - Because it suppresses attenuation artifacts from the diaphragm, prone SPECT is
      suitable for evaluating the cardiac inferior wall. A solid-state dedicated
      cardiac camera allows upright imaging, which can also be used to avoid
      attenuation artifacts from the diaphragm. We compared prone and upright imaging
      for inferior wall evaluation using 201TlCl myocardial perfusion SPECT (MPS).
      Methods: The study targeted 45 patients. The prone imaging group included 23
      subjects who underwent additional prone imaging because supine imaging indicated
      that the inferior wall had reduced uptake. The upright imaging group included 22
      subjects who, in the past, had shown reduced uptake in the inferior wall during
      supine imaging. Using the MPS stress images and analysis software, we created a
      polar map showing the incorporation of the radioisotope throughout the whole of
      the myocardium; this polar map was then classified into 17 segments. The
      percentage uptake ratios of the inferior/anterior wall were calculated for the
      prone and upright acquisitions. These ratios were used as the ratio of percentage
      uptake in each segment of the anterior wall to percentage uptake in each segment
      of the inferior wall. In addition, 6 reviewers visually evaluated the uniformity
      within the inferior wall for both the prone and the upright imaging. Results:
      There was a significant difference in percentage uptake ratios between the prone
      and upright images in segments 4/1 (basal inferior/basal anterior; P < 0.05),
      11/12 (mid inferolateral/mid anterolateral; P < 0.001), and 15/13 (apical
      inferior/apical anterior; P < 0.05). There were no significant differences
      between the prone and upright images in visual evaluations of uniformity within
      the inferior wall. Conclusion: In comparison with upright imaging, prone imaging
      has a higher rate of suppression of attenuation artifacts from the diaphragm.
      However, this difference does not seem to affect the images visually. Therefore,
      upright and prone imaging can be used interchangeably to evaluate the inferior
      wall.

PMID- 29042471
TI  - Adapting a Standardized, Industry-Proven Tool to Measure Patients' Perceptions of
      Quality at the Point of Care in a PET/CT Center.
AB  - Patient satisfaction with health-care delivery is essential today. Using a
      psychometrically validated questionnaire-SERVPERF-we quantitatively measured
      patients' perceptions of the quality of service at the point of care in a PET/CT
      center, and we used this information to guide subsequent quality improvement
      interventions. SERVPERF is a survey instrument that measures performance for
      various services. It has demonstrated reliability and validity across various
      industries. The standard for measuring patient perception of quality in hospitals
      the "Hospital Consumer Assessment of Health Care Providers and Systems" survey
      does not include questions about the care received in a typical radiology
      department and is not performed at the point of care. Methods: 429 patients
      undergoing PET/CT examinations filled out an anonymous modified SERVPERF
      questionnaire on completion of imaging and reported their level of agreement with
      each of the 27 items by circling a Likert-type scale from 1 to 7. Each item was
      designed to elicit a response on the patient's perception of performance on a
      metric of quality. Data were summarized as the mean of each item. The frequency
      of low scores (<=3) was also calculated. Results: The items with the lowest mean
      score were "The department's physical facilities are visually appealing" (6.158)
      and "Documentation such as sign-in sheet, handouts, and brochures are visually
      appealing" (6.162). The item with the highest frequency of low scores (<=3) was,
      "The department provides services at the promised time" (11/429 responses).
      Conclusion: Our study showed that patient perception of quality in a diagnostic
      radiology department can be measured with a standardized survey at the point of
      care delivery and used to direct patient-centered quality improvement
      interventions.

PMID- 29042472
TI  - Technical Advances in Image Guidance of Radionuclide Therapy.
AB  - Internal radiation therapy with radionuclides (i.e., radionuclide therapy) owes
      its success to the many advantages over other, more conventional, treatment
      options. One distinct advantage of radionuclide therapies is the potential to use
      (part of) the emitted radiation for imaging of the radionuclide distribution. The
      combination of diagnostic and therapeutic properties in a set of matched
      radiopharmaceuticals (sometimes combined in a single radiopharmaceutical) is
      often referred to as theranostics and allows accurate diagnostic imaging before
      therapy. The use of imaging benefits treatment planning, dosimetry, and
      assessment of treatment response. This paper focuses on a selection of advances
      in imaging technology relevant for image guidance of radionuclide therapy. This
      involves developments in nuclear imaging modalities, as well as other anatomic
      and functional imaging modalities. The quality and quantitative accuracy of
      images used for guidance of radionuclide therapy is continuously being improved,
      which in turn may improve the therapeutic outcome and efficiency of radionuclide
      therapies.

PMID- 29042473
TI  - Pharmacologic Stress Testing with MyocardialPerfusion Imaging.
AB  - The preferred method for performing stress testing with myocardial perfusion
      imaging is physical exercise. However, many patients are unable to reach an
      adequate endpoint. As an alternative, various pharmacologic options are
      available, which are explored in this article.

PMID- 29042474
TI  - Development of a PET/CT and PET/MRI patient information films in collaboration
      with patient representatives previously treated for cancer.
AB  - Introduction: PET/MRI and PET CT scanning carries an increased psychological
      burden for patients which may be improved by effective preparation prior to
      attendance for the procedure. We aimed to devise an online resource for patient
      benefit prior to PET/MRI and PET/CT scanning. Methods: With the help of patient
      representatives' the style and content for two patient information films was
      reviewed at each stage of the process to explain the patient journey. Results:
      Two patient information films were produced for patients undergoing PET scanning,
      Positive feedback from healthcare providers and users was obtained. Conclusion:
      Involvement of patient representatives in the production of an information
      resource has had a positive impact on the finished product, with potential for
      increased benefit to patients as a result.

PMID- 29042475
TI  - Mitotic bookmarking in development and stem cells.
AB  - The changes imposed on the nucleus, chromatin and its regulators during mitosis
      lead to the dismantlement of most gene regulatory processes. However, an
      increasing number of transcriptional regulators are being identified as capable
      of binding their genomic targets during mitosis. These so-called 'mitotic
      bookmarking factors' encompass transcription factors and chromatin modifiers that
      are believed to convey gene regulatory information from mother to daughter cells.
      In this Primer, we review mitotic bookmarking processes in development and stem
      cells and discuss the interest and potential importance of this concept with
      regard to epigenetic regulation and cell fate transitions involving cellular
      proliferation.

PMID- 29042476
TI  - The three-dimensional genome: regulating gene expression during pluripotency and
      development.
AB  - The precise expression of genes in time and space during embryogenesis is largely
      influenced by communication between enhancers and promoters, which is propagated
      and governed by the physical proximity of these elements in the nucleus. Here, we
      review how chromatin domains organize the genome by guiding enhancers to their
      target genes thereby preventing non-specific interactions with other neighboring
      regions. We also discuss the dynamics of chromatin interactions between enhancers
      and promoters, as well as the consequent changes in gene expression, that occur
      in pluripotent cells and during development. Finally, we evaluate how genomic
      changes such as deletions, inversions and duplications affect 3D chromatin
      configuration overall and lead to ectopic enhancer-promoter contacts, and thus
      gene misexpression, which can contribute to abnormal development and disease.

PMID- 29042477
TI  - KDM3A-mediated demethylation of histone H3 lysine 9 facilitates the chromatin
      binding of Neurog2 during neurogenesis.
AB  - Neurog2 is a crucial regulator of neuronal fate specification and differentiation
      in vivo and in vitro However, it remains unclear how Neurog2 transactivates
      neuronal genes that are silenced by repressive chromatin. Here, we provide
      evidence that the histone H3 lysine 9 demethylase KDM3A facilitates the Xenopus
      Neurog2 (formerly known as Xngnr1) chromatin accessibility during neuronal
      transcription. Loss-of-function analyses reveal that KDM3A is not required for
      the transition of naive ectoderm to neural progenitor cells but is essential for
      primary neuron formation. ChIP series followed by qPCR analyses reveal that
      Neurog2 promotes the removal of the repressive H3K9me2 marks and addition of
      active histone marks, including H3K27ac and H3K4me3, at the NeuroD1 and Tubb2b
      promoters; this activity depends on the presence of KDM3A because Neurog2, via
      its C-terminal domain, interacts with KDM3A. Interestingly, KDM3A is dispensable
      for the neuronal transcription initiated by Ascl1, a proneural factor related to
      neurogenin in the bHLH family. In summary, our findings uncover a crucial role
      for histone H3K9 demethylation during Neurog2-mediated neuronal transcription and
      help in the understanding of the different activities of Neurog2 and Ascl1 in
      initiating neuronal development.

PMID- 29042478
TI  - Correction: SoxF factors induce Notch1 expression via direct transcriptional
      regulation during early arterial development. Development doi:
      10.1242/dev.146241.

PMID- 29042479
TI  - Retraction: Eya1 controls cell polarity, spindle orientation, cell fate and Notch
      signaling in distal embryonic lung epithelium. Development doi:
      10.1242/dev.058479.

PMID- 29042480
TI  - Prediction of Protein Complexes in Trypanosoma brucei by Protein Correlation
      Profiling Mass Spectrometry and Machine Learning.
AB  - A disproportionate number of predicted proteins from the genome sequence of the
      protozoan parasite Trypanosoma brucei, an important human and animal pathogen,
      are hypothetical proteins of unknown function. This paper describes a protein
      correlation profiling mass spectrometry approach, using two size exclusion and
      one ion exchange chromatography systems, to derive sets of predicted protein
      complexes in this organism by hierarchical clustering and machine learning
      methods. These hypothesis-generating proteomic data are provided in an open
      access online data visualization environment
      (http://134.36.66.166:8083/complex_explorer). The data can be searched
      conveniently via a user friendly, custom graphical interface. We provide examples
      of both potential new subunits of known protein complexes and of novel
      trypanosome complexes of suggested function, contributing to improving the
      functional annotation of the trypanosome proteome. Data are available via
      ProteomeXchange with identifier PXD005968.

PMID- 29042482
TI  - Resveratrol stimulates the metabolic reprogramming of human CD4+ T cells to
      enhance effector function.
AB  - The polyphenol resveratrol activates the deacetylase Sirt1, resulting in various
      antioxidant, chemoprotectant, neuroprotective, cardioprotective, and anti
      inflammatory properties. We found that at high concentrations of resveratrol,
      human CD4+ T cells showed defective antigen receptor signaling and arrest at the
      G1 stage of the cell cycle, whereas at low concentrations, cells were readily
      activated and exhibited enhanced Sirt1 deacetylase activity. Nevertheless, low
      dose resveratrol rapidly stimulated genotoxic stress in the T cells, which
      resulted in engagement of a DNA damage response pathway that depended on the
      kinase ATR [ataxia telangiectasia-mutated (ATM) and Rad3-related], but not ATM,
      and subsequently in premitotic cell cycle arrest. The concomitant activation of
      p53 was coupled to the expression of gene products that regulate cell metabolism,
      leading to a metabolic reprogramming that was characterized by decreased
      glycolysis, increased glutamine consumption, and a shift to oxidative
      phosphorylation. These alterations in the bioenergetic homeostasis of CD4+ T
      cells resulted in enhanced effector function, with both naive and memory CD4+ T
      cells secreting increased amounts of the inflammatory cytokine interferon-gamma.
      Thus, our data highlight the wide range of metabolic adaptations that CD4+ T
      lymphocytes undergo in response to genomic stress.

PMID- 29042481
TI  - The matricellular protein TSP1 promotes human and mouse endothelial cell
      senescence through CD47 and Nox1.
AB  - Senescent cells withdraw from the cell cycle and do not proliferate. The
      prevalence of senescent compared to normally functioning parenchymal cells
      increases with age, impairing tissue and organ homeostasis. A contentious
      principle governing this process has been the redox theory of aging. We linked
      matricellular protein thrombospondin 1 (TSP1) and its receptor CD47 to the
      activation of NADPH oxidase 1 (Nox1), but not of the other closely related Nox
      isoforms, and associated oxidative stress, and to senescence in human cells and
      aged tissue. In human endothelial cells, TSP1 promoted senescence and attenuated
      cell cycle progression and proliferation. At the molecular level, TSP1 increased
      Nox1-dependent generation of reactive oxygen species (ROS), leading to the
      increased abundance of the transcription factor p53. p53 mediated a DNA damage
      response that led to senescence through Rb and p21cip, both of which inhibit cell
      cycle progression. Nox1 inhibition blocked the ability of TSP1 to increase p53
      nuclear localization and p21cip abundance and its ability to promote senescence.
      Mice lacking TSP1 showed decreases in ROS production, p21cip expression, p53
      activity, and aging-induced senescence. Conversely, lung tissue from aging humans
      displayed increases in the abundance of vascular TSP1, Nox1, p53, and p21cip
      Finally, genetic ablation or pharmacological blockade of Nox1 in human
      endothelial cells attenuated TSP1-mediated ROS generation, restored cell cycle
      progression, and protected against senescence. Together, our results provide
      insights into the functional interplay between TSP1 and Nox1 in the regulation of
      endothelial senescence and suggest potential targets for controlling the aging
      process at the molecular level.

PMID- 29042484
TI  - Accuracy of Oxygen Flow Delivered by Compressed-Gas Cylinders in Hospital and
      Prehospital Emergency Care.
AB  - BACKGROUND: Oxygen cylinders are widely used both in hospital and prehospital
      care. Excessive or inappropriate FIO2 may be critical for patients with
      hypercapnia or hypoxia. Moreover, over-oxygenation could be deleterious in
      ischemic disorders. Supplemental oxygen from oxygen cylinder should therefore be
      delivered accurately. The aim of this study was to assess the accuracy of oxygen
      flows for oxygen cylinder in hospital and prehospital care. METHODS: A
      prospective trial was conducted to evaluate accuracy of delivered oxygen flows
      (2, 4, 6, 9 and 12 L/min) for different oxygen cylinder ready for use in
      different hospital departments. Delivered flows were analyzed randomly using a
      calibrated thermal mass flow meter. Two types of oxygen cylinder were evaluated:
      78 oxygen cylinder with a single-stage regulator and 70 oxygen cylinder with a
      dual-stage regulator. Delivered flows were compared to the required oxygen flow.
      The residual pressure value for each oxygen cylinder was considered. A
      coefficient of variation was calculated to compare the variability of the
      delivered flow between the two types of oxygen cylinder. RESULTS: The median
      values of delivered flows were all >= 100% of the required flow for single stage
      (range 100-109%) and < 100% of required flow for dual stage (range 95-97%). The
      median values of the delivered flow differed between single and dual stage. It
      was found that single stage is significantly higher than dual stage (P = .01). At
      low flow, the dispersion of the measures for single stage was higher than with a
      high oxygen flow. Delivered flow differences were also found between low and high
      residual pressures, but only with single stage (P = .02). The residual pressure
      for both oxygen cylinders (no. = 148) ranged from 73 to 2,900 pounds per square
      inch, and no significant difference was observed between the 2 types (P = .86).
      The calculated coefficient of variation ranged from 7% (+/-1%) for dual stage to
      8% (+/-2%) for single stage. CONCLUSIONS: This study shows good accuracy of
      oxygen flow delivered via oxygen cylinders. This accuracy was higher with dual
      stage. Single stage was also accurate, however, at low flow this accuracy is
      slightly less. Moreover, with single stage, when residual pressure decreases, the
      median value of delivered flow decreased.

PMID- 29042483
TI  - Olfactory experience primes the heat shock transcription factor HSF-1 to enhance
      the expression of molecular chaperones in C. elegans.
AB  - Learning, a process by which animals modify their behavior as a result of
      experience, enables organisms to synthesize information from their surroundings
      to acquire resources and avoid danger. We showed that a previous encounter with
      only the odor of pathogenic bacteria prepared Caenorhabditis elegans to survive
      exposure to the pathogen by increasing the heat shock factor 1 (HSF-1)-dependent
      expression of genes encoding molecular chaperones. Experience-mediated
      enhancement of chaperone gene expression required serotonin, which primed HSF-1
      to enhance the expression of molecular chaperone genes by promoting its
      localization to RNA polymerase II-enriched nuclear loci, even before
      transcription occurred. However, HSF-1-dependent chaperone gene expression was
      stimulated only if and when animals encountered the pathogen. Thus, learning
      equips C. elegans to better survive environmental dangers by preemptively and
      specifically initiating transcriptional mechanisms throughout the whole organism
      that prepare the animal to respond rapidly to proteotoxic agents. These studies
      provide one plausible basis for the protective role of environmental enrichment
      in disease.

PMID- 29042485
TI  - Maternal Stress During Pregnancy and Allergic Diseases in Children During the
      First Year of Life.
AB  - BACKGROUND: Many recent studies indicate that prenatal maternal distress
      increases the risk of allergic diseases in children. The mechanisms that favor it
      are still unclear. OBJECTIVES: We aimed to assess the association between
      exposure to different kinds of prenatal stress and the occurrence of atopic
      dermatitis, food allergy, wheezing, and recurrent respiratory tract infections in
      children. METHODS: The study population consisted of 370 mother-child pairs from
      a Polish Mother and Child Cohort (REPRO_PL). The analysis was restricted to the
      women who worked at least one month during the pregnancy period. Maternal
      psychological stress during pregnancy was assessed based on the Subjective Work
      Characteristics Questionnaire, the Perceived Stress Scale, and the Social
      Readjustment Rating Scale. The presence of atopic dermatitis, food allergy,
      wheezing, and recurrent respiratory tract infections in children was evaluated by
      doctors at 12 months of age. RESULTS: In a univariate model, we showed
      significant association between maternal life stress (according to the Perceived
      Stress Scale) and stressful life events (according to the Social Readjustment
      Rating Scale) and infant wheezing (at least 1 episode of wheezing during the
      first year of life). A multivariate model of logistic regression analysis
      revealed that maternal stress during pregnancy, described by the Social
      Readjustment Rating Scale, increased the risk of wheezing in children (OR 1.09,
      95% CI 1.01-1.02) independently from other predictors of wheezing previously
      determined in this cohort, such as the number of infections and maternal smoking.
      We observed also significant positive association between maternal life stress
      during pregnancy measured by the Perceived Stress Scale and the risk of recurrent
      respiratory tract infections in the first year of life, however it was not
      significant after adjustment for confounding variables. CONCLUSIONS: Maternal
      stress during pregnancy increases the risk of childhood wheezing. The effects of
      stress during pregnancy on the onset of allergic diseases in children should be
      developed and translated into early prevention strategies.

PMID- 29042486
TI  - Parameters for Simulation of Adult Subjects During Mechanical Ventilation.
AB  - BACKGROUND: Simulation studies are often used to examine ventilator performance.
      However, there are no standards for selecting simulation parameters. This study
      collected data in passively-ventilated adult human subjects and summarized the
      results as a set of parameters that can be used for simulation studies of
      intubated, passive, adult subjects with normal lungs, COPD, or ARDS. METHODS:
      Consecutive adult patients admitted to the ICU were included if they were deeply
      sedated and mechanically ventilated for <48 h without any spontaneous breathing
      activity. Subjects were classified as having normal lungs, COPD, or ARDS.
      Respiratory mechanics variables were collected once per subject. Static
      compliance was calculated as the ratio between tidal volume and driving pressure.
      Inspiratory resistance was measured by the least-squares fitting method. The
      expiratory time constant was estimated by the tidal volume/flow ratio. RESULTS:
      Of the 359 subjects included, 138 were classified as having normal lungs, 181 as
      ARDS, and 40 as COPD. Median (interquartile range) static compliance was
      significantly lower in ARDS subjects as compared with normal lung and COPD
      subjects (39 [32-50] mL/cm H2O vs 54 [44-64] and 59 [43-75] mL/cm H2O,
      respectively, P < .001). Inspiratory resistance was significantly higher in COPD
      subjects as compared with normal lung and ARDS subjects (22 [16-33] cm H2O/L/s vs
      13 [10-15] and 12 [9-14] cm H2O/L/s, respectively, P < .001). The expiratory time
      constant was significantly different for each lung condition (0.60 [0.51-0.71],
      1.07 [0.68-2.14], and 0.46 [0.40-0.55] s for normal lung, COPD, and ARDS
      subjects, respectively, P < .001). In the subgroup of subjects with ARDS, there
      were no significant differences in respiratory mechanics variables among mild,
      moderate, and severe ARDS. CONCLUSIONS: This study provides educators,
      researchers, and manufacturers with a standard set of practical parameters for
      simulating the respiratory system's mechanical properties in passive conditions.

PMID- 29042487
TI  - Differential Response of Glioma Stem Cells to Arsenic Trioxide Therapy Is
      Regulated by MNK1 and mRNA Translation.
AB  - Mesenchymal (MES) and proneural (PN) are two distinct glioma stem cell (GSC)
      populations that drive therapeutic resistance in glioblastoma (GBM). We screened
      a panel of 650 small molecules against patient-derived GBM cells to discover
      compounds targeting specific GBM subtypes. Arsenic trioxide (ATO), an FDA
      approved drug that crosses the blood-brain barrier, was identified as a potent PN
      specific compound in the initial screen and follow-up validation studies.
      Furthermore, MES and PN GSCs exhibited differential sensitivity to ATO. As ATO
      has been shown to activate the MAPK-interacting kinase 1 (MNK1)-eukaryotic
      translation initiation factor 4E (eIF4E) pathway and subsequent mRNA translation
      in a negative regulatory feedback manner, the mechanistic role of ATO resistance
      in MES GBM was explored. In GBM cells, ATO-activated translation initiation
      cellular events via the MNK1-eIF4E signaling axis. Furthermore, resistance to ATO
      in intracranial PDX tumors correlated with high eIF4E phosphorylation. Polysomal
      fractionation and microarray analysis of GBM cells were performed to identify
      ATO's effect on mRNA translation and enrichment of anti-apoptotic mRNAs in the
      ATO-induced translatome was found. Additionally, it was determined that MNK
      inhibition sensitized MES GSCs to ATO in neurosphere and apoptosis assays.
      Finally, examination of the effect of ATO on patients from a phase I/II clinical
      trial of ATO revealed that PN GBM patients responded better to ATO than other
      subtypes as demonstrated by longer overall and progression-free
      survival.Implications: These findings raise the possibility of a unique
      therapeutic approach for GBM, involving MNK1 targeting to sensitize MES GSCs to
      drugs like arsenic trioxide. Mol Cancer Res; 16(1); 32-46. (c)2017 AACR.

PMID- 29042488
TI  - Natural killer cells mediate pathophysiology in response to reduced uterine
      perfusion pressure.
AB  - Preeclampsia is associated with hypertension, small-for-gestational-age babies,
      and increased cytolytic natural killer (NK) cells. The specific role of cytolytic
      NK cells in the pathophysiology of preeclampsia has not been clearly defined. We
      hypothesized that Reduced Uterine Perfusion Pressure (RUPP) stimulates
      proliferation and cytolytic activation of NK cells, and that reducing NK cells in
      RUPP would prevent hypertension, intrauterine growth restriction, and
      inflammation in response to placental ischemia. RUPP was induced on gestation day
      (GD) 14 in pregnant rats. NK cells were depleted by i.p. administration of anti
      asialo GM1 antibody on GDs 15 and 17. Placental and circulating NK cells were
      quantified via flow cytometry, mean arterial pressure (MAP), fetal weights, and
      cytokines were measured on GD 19. Total placental NK cells were 7.4 +/- 2% of
      gated cells in normal pregnant (NP; n=10) and 16.5 +/- 3% of gated cells in RUPP
      (n=10) rats. Furthermore, cytolytic placental NK cells also increased in RUPP.
      Depletion of NK cells in RUPP (RUPP + anti-ASGM1) significantly improved MAP and
      fetal weights. MAP was 108 +/- 2 mmHg in NP, 125 +/- 2 mmHg in RUPP, and 112 +/-
      2 mmHg in RUPP + anti-ASGM1 (n=12). Fetal weight was 2.32 +/- 0.05 in NP, 1.8 +/-
      0.04g in RUPP, and increased to 2.0 +/- 0.04g in RUPP + anti-ASGM1. Placental
      interferon-gamma (IFN-gamma) was 40.4 +/- 5.2 pg/mg in NP, 72.17 +/- 3.2 pg/mg in
      RUPP, and 44.0 +/- 6.5 pg/mg in RUPP + anti-ASGM1 (P<0.05). Placental tumor
      necrosis factor-alpha (TNF-alpha) was 17.9 +/- 1.7 pg/mg in NP, 23.9 +/- 2.2
      pg/mg in RUPP, and 12.9 +/- 2.3 pg/mg in RUPP + anti-ASGM1 (P<0.05). Depletion of
      NK cells significantly lowered MAP, intrauterine growth restriction, and
      inflammation in RUPP rats indicating that cytolytic NK cells are important in
      preeclampsia pathophysiology.

PMID- 29042489
TI  - Alterations in endothelin type B receptor contribute to microvascular dysfunction
      in women who have had preeclampsia.
AB  - Microvascular dysfunction originating during a preeclamptic pregnancy persists
      postpartum and probably contributes to increased CVD risk in these women. One
      putative mechanism contributing to this dysfunction is increased vasoconstrictor
      sensitivity to endothelin-1 (ET-1), mediated by alterations in ET-1 receptor type
      B (ETBR). We evaluated ET-1 sensitivity, ETAR, and ETBR contributions to ET-1
      mediated constriction, and the mechanistic role of ETBR in endothelium-dependent
      dilation in vivo in the microvasculature of postpartum women who had preeclampsia
      (PrEC, n=12) and control women who had a healthy pregnancy (HC, n=12). We
      hypothesized that (1) PrEC would have a greater vasoconstrictor response to ET-1,
      and (2) reduced ETBR-mediated dilation. We further hypothesized that ETBR
      blockade would attenuate endothelium-dependent vasodilation in HC, but not PrEC.
      Microvascular reactivity was assessed by measurement of cutaneous vascular
      conductance responses to graded infusion of ET-1 (10-20-10-8 mol/l), ET-1 + 500
      nmol/l BQ-123 (ETAR-blockade), and ET-1 + 300 nmol/l BQ-788 (ETBR-blockade), and
      during graded infusion of acetylcholine (ACh, 10-7-102 mmol/l) and a standardized
      local heating protocol with and without ETBR-inhibition. PrEC had an increased
      vasoconstriction response to ET-1 (P=0.02). PrEC demonstrated reduced dilation
      responses to selective ETBR stimulation with ET-1 (P=0.01). ETBR-inhibition
      augmented ET-1-mediated constriction in HC (P=0.01) but attenuated ET-1-mediated
      constriction in PrEC (P=0.003). ETBR-inhibition attenuated endothelium-dependent
      vasodilation responses to 100mmol/l ACh (P=0.04) and local heat (P=0.003) in HC
      but increased vasodilation (ACh: P=0.01; local heat: P=0.03) in PrEC. Women who
      have had preeclampsia demonstrate augmented vasoconstrictor sensitivity to ET-1,
      mediated by altered ETBR signaling. Furthermore, altered ETBR function
      contributes to diminished endothelium-dependent dilation in previously
      preeclamptic women.

PMID- 29042490
TI  - Remote Ischemic Conditioning May Improve Outcomes of Patients With Cerebral Small
      Vessel Disease.
AB  - BACKGROUND AND PURPOSE: We aimed to evaluate the efficacy of remote ischemic
      conditioning (RIC) in patients with cerebral small-vessel disease. METHODS:
      Thirty patients with cerebral small-vessel disease-related mild cognitive
      impairment were enrolled in this prospective, randomized controlled study for 1
      year. Besides routine medical treatment, participants were randomized into the
      experimental group (n=14) undergoing 5 cycles consisting of ischemia followed by
      reperfusion for 5 minutes on both upper limbs twice daily for 1 year or the
      control group (n=16) who were treated with sham ischemia-reperfusion cycles. The
      primary outcome was the change of brain lesions, and secondary outcomes were
      changes of cognitive function, plasma biomarkers, and cerebral hemodynamic
      parameters both at baseline and at the end of 1-year follow-up. RESULTS: Compared
      with pretreatment, the post-treatment white matter hyperintensities volume in the
      RIC group was significantly reduced (9.10+/-7.42 versus 6.46+/-6.05 cm3;
      P=0.020), whereas no significant difference was observed in the sham-RIC group
      (8.99+/-6.81 versus 8.07+/-6.56 cm3; P=0.085). The reduction of white matter
      hyperintensities volume in the RIC group was more substantial than that in sham
      group (-2.632 versus -0.935 cm3; P=0.049). No significant difference was found in
      the change of the number of lacunes between 2 groups (0 versus 0; P=0.694). A
      significant treatment difference at 1 year on visuospatial and executive ability
      was found between the 2 groups (0.639 versus 0.191; P=0.048). RIC showed greater
      effects compared with sham-RIC on plasma triglyceride (-0.433 versus 0.236
      mmol/L; P=0.005), total cholesterol (-0.975 versus 0.134 mmol/L; P<0.001), low
      density lipoprotein (-0.645 versus -0.029 mmol/L; P=0.034), and homocysteine (
      4.737 versus -1.679 umol/L; P=0.044). Changes of the pulsation indices of middle
      cerebral arteries from the baseline to 1 year were different between the 2 groups
      (right: -0.075 versus 0.043; P=0.030; left: -0.085 versus 0.043; P=0.010).
      CONCLUSIONS: RIC seems to be potentially effective in patients with cerebral
      small-vessel disease in slowing cognition decline and reducing white matter
      hyperintensities. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01658306.

PMID- 29042491
TI  - Using the Telephone Interview for Cognitive Status and Telephone Montreal
      Cognitive Assessment for Evaluating Vascular Cognitive Impairment: Promising Call
      or Put on Hold?

PMID- 29042492
TI  - Validation of the Telephone Interview of Cognitive Status and Telephone Montreal
      Cognitive Assessment Against Detailed Cognitive Testing and Clinical Diagnosis of
      Mild Cognitive Impairment After Stroke.
AB  - BACKGROUND AND PURPOSE: Assessment of cognitive status poststroke is recommended
      by guidelines but follow-up can often not be done in person. The Telephone
      Interview of Cognitive Status (TICS) and the Telephone Montreal Cognitive
      Assessment (T-MoCA) are considered useful screening instruments. Yet, evidence to
      define optimal cut-offs for mild cognitive impairment (MCI) after stroke is
      limited. METHODS: We studied 105 patients enrolled in the prospective DEDEMAS
      study (Determinants of Dementia After Stroke; NCT01334749). Follow-up visits at
      6, 12, 36, and 60 months included comprehensive neuropsychological testing and
      the Clinical Dementia Rating scale, both of which served as reference standards.
      The original TICS and T-MoCA were obtained in 2 separate telephone interviews
      each separated from the personal visits by 1 week (1 before and 1 after the
      visit) with the order of interviews (TICS versus T-MoCA) alternating between
      subjects. Area under the receiver-operating characteristic curves was determined.
      RESULTS: Ninety-six patients completed both the face-to-face visits and the 2
      interviews. Area under the receiver-operating characteristic curves ranged
      between 0.76 and 0.83 for TICS and between 0.73 and 0.94 for T-MoCA depending on
      MCI definition. For multidomain MCI defined by multiple-tests definition derived
      from comprehensive neuropsychological testing optimal sensitivities and
      specificities were achieved at cut-offs <36 (TICS) and <18 (T-MoCA). Validity was
      lower using single-test definition, and cut-offs were higher compared with
      multiple-test definitions. Using Clinical Dementia Rating as the reference,
      optimal cut-offs for MCI were <36 (TICS) and approximately 19 (T-MoCA).
      CONCLUSIONS: Both the TICS and T-MoCA are valid screening tools poststroke,
      particularly for multidomain MCI using multiple-test definition.

PMID- 29042494
TI  - Insights from the Genome Sequence of Mycobacterium lepraemurium: Massive Gene
      Decay and Reductive Evolution.
AB  - Mycobacterium lepraemurium is the causative agent of murine leprosy, a chronic,
      granulomatous disease similar to human leprosy. Due to the similar clinical
      manifestations of human and murine leprosy and the difficulty of growing both
      bacilli axenically, Mycobacterium leprae and M. lepraemurium were once thought to
      be closely related, although it was later suggested that M. lepraemurium might be
      related to Mycobacterium avium In this study, the complete genome of M.
      lepraemurium was sequenced using a combination of PacBio and Illumina sequencing.
      Phylogenomic analyses confirmed that M. lepraemurium is a distinct species within
      the M. avium complex (MAC). The M. lepraemurium genome is 4.05 Mb in length,
      which is considerably smaller than other MAC genomes, and it comprises 2,682
      functional genes and 1,139 pseudogenes, which indicates that M. lepraemurium has
      undergone genome reduction. An error-prone repair homologue of the DNA polymerase
      III alpha-subunit was found to be nonfunctional in M. lepraemurium, which might
      contribute to pseudogene formation due to the accumulation of mutations in
      nonessential genes. M. lepraemurium has retained the functionality of several
      genes thought to influence virulence among members of the
      MAC.IMPORTANCEMycobacterium lepraemurium seems to be evolving toward a minimal
      set of genes required for an obligatory intracellular lifestyle within its host,
      a niche seldom adopted by most mycobacteria, as they are free-living. M.
      lepraemurium could be used as a model to elucidate functions of genes shared with
      other members of the MAC. Its reduced gene set can be exploited for studying the
      essentiality of genes in related pathogenic species, which might lead to
      discovery of common virulence factors or clarify host-pathogen interactions. M.
      lepraemurium can be cultivated in vitro only under specific conditions and even
      then with difficulty. Elucidating the metabolic (in)capabilities of M.
      lepraemurium will help develop suitable axenic media and facilitate genetic
      studies.

PMID- 29042493
TI  - Unraveling the Self-Assembly of the Pseudomonas aeruginosa XcpQ Secretin
      Periplasmic Domain Provides New Molecular Insights into Type II Secretion System
      Secreton Architecture and Dynamics.
AB  - The type II secretion system (T2SS) releases large folded exoproteins across the
      envelope of many Gram-negative pathogens. This secretion process therefore
      requires specific gating, interacting, and dynamics properties mainly operated by
      a bipartite outer membrane channel called secretin. We have a good understanding
      of the structure-function relationship of the pore-forming C-terminal domain of
      secretins. In contrast, the high flexibility of their periplasmic N-terminal
      domain has been an obstacle in obtaining the detailed structural information
      required to uncover its molecular function. In Pseudomonas aeruginosa, the Xcp
      T2SS plays an important role in bacterial virulence by its capacity to deliver a
      large panel of toxins and degradative enzymes into the surrounding environment.
      Here, we revealed that the N-terminal domain of XcpQ secretin spontaneously self
      assembled into a hexamer of dimers independently of its C-terminal domain.
      Furthermore, and by using multidisciplinary approaches, we elucidate the
      structural organization of the XcpQ N domain and demonstrate that secretin
      flexibility at interdimer interfaces is mandatory for its function.IMPORTANCE
      Bacterial secretins are large homooligomeric proteins constituting the outer
      membrane pore-forming element of several envelope-embedded nanomachines essential
      in bacterial survival and pathogenicity. They comprise a well-defined membrane
      embedded C-terminal domain and a modular periplasmic N-terminal domain involved
      in substrate recruitment and connection with inner membrane components. We are
      studying the XcpQ secretin of the T2SS present in the pathogenic bacterium
      Pseudomonas aeruginosa Our data highlight the ability of the XcpQ N-terminal
      domain to spontaneously oligomerize into a hexamer of dimers. Further in vivo
      experiments revealed that this domain adopts different conformations essential
      for the T2SS secretion process. These findings provide new insights into the
      functional understanding of bacterial T2SS secretins.

PMID- 29042495
TI  - Impact of Dietary Resistant Starch on the Human Gut Microbiome, Metaproteome, and
      Metabolome.
AB  - Diet can influence the composition of the human microbiome, and yet relatively
      few dietary ingredients have been systematically investigated with respect to
      their impact on the functional potential of the microbiome. Dietary resistant
      starch (RS) has been shown to have health benefits, but we lack a mechanistic
      understanding of the metabolic processes that occur in the gut during digestion
      of RS. Here, we collected samples during a dietary crossover study with diets
      containing large or small amounts of RS. We determined the impact of RS on the
      gut microbiome and metabolic pathways in the gut, using a combination of "omics"
      approaches, including 16S rRNA gene sequencing, metaproteomics, and metabolomics.
      This multiomics approach captured changes in the abundance of specific bacterial
      species, proteins, and metabolites after a diet high in resistant starch (HRS),
      providing key insights into the influence of dietary interventions on the gut
      microbiome. The combined data showed that a high-RS diet caused an increase in
      the ratio of Firmicutes to Bacteroidetes, including increases in relative
      abundances of some specific members of the Firmicutes and concurrent increases in
      enzymatic pathways and metabolites involved in lipid metabolism in the
      gut.IMPORTANCE This work was undertaken to obtain a mechanistic understanding of
      the complex interplay between diet and the microorganisms residing in the
      intestine. Although it is known that gut microbes play a key role in digestion of
      the food that we consume, the specific contributions of different microorganisms
      are not well understood. In addition, the metabolic pathways and resultant
      products of metabolism during digestion are highly complex. To address these
      knowledge gaps, we used a combination of molecular approaches to determine the
      identities of the microorganisms in the gut during digestion of dietary starch as
      well as the metabolic pathways that they carry out. Together, these data provide
      a more complete picture of the function of the gut microbiome in digestion,
      including links between an RS diet and lipid metabolism and novel linkages
      between specific gut microbes and their metabolites and proteins produced in the
      gut.

PMID- 29042496
TI  - Structural Basis of Type 2 Secretion System Engagement between the Inner and
      Outer Bacterial Membranes.
AB  - Sophisticated nanomachines are used by bacteria for protein secretion. In Gram
      negative bacteria, the type 2 secretion system (T2SS) is composed of a
      pseudopilus assembly platform in the inner membrane and a secretin complex in the
      outer membrane. The engagement of these two megadalton-sized complexes is
      required in order to secrete toxins, effectors, and hydrolytic enzymes.
      Pseudomonas aeruginosa has at least two T2SSs, with the ancestral nanomachine
      having a secretin complex composed of XcpQ. Until now, no high-resolution
      structural information was available to distinguish the features of this
      Pseudomonas-type secretin, which varies greatly in sequence from the well
      characterized Klebsiella-type and Vibrio-type secretins. We have purified the ~1
      MDa secretin complex and analyzed it by cryo-electron microscopy. Structural
      comparisons with the Klebsiella-type secretin complex revealed a striking
      structural homology despite the differences in their sequence characteristics. At
      3.6-A resolution, the secretin complex was found to have 15-fold symmetry
      throughout the membrane-embedded region and through most of the domains in the
      periplasm. However, the N1 domain and N0 domain were not well ordered into this
      15-fold symmetry. We suggest a model wherein this disordering of the subunit
      symmetry for the periplasmic N domains provides a means to engage with the 6-fold
      symmetry in the inner membrane platform, with a metastable engagement that can be
      disrupted by substrate proteins binding to the region between XcpP, in the
      assembly platform, and the XcpQ secretin.IMPORTANCE How the outer membrane and
      inner membrane components of the T2SS engage each other and yet can allow for
      substrate uptake into the secretin chamber has challenged the protein transport
      field for some time. This vexing question is of significance because the T2SS
      collects folded protein substrates in the periplasm for transport out of the
      bacterium and yet must discriminate these few substrate proteins from all the
      other hundred or so folded proteins in the periplasm. The structural analysis
      here supports a model wherein substrates must compete against a metastable
      interaction between XcpP in the assembly platform and the XcpQ secretin, wherein
      only structurally encoded features in the T2SS substrates compete well enough to
      disrupt XcpQ-XcpP for entry into the XcpQ chamber, for secretion across the outer
      membrane.

PMID- 29042497
TI  - A Single Dual-Function Enzyme Controls the Production of Inflammatory NOD Agonist
      Peptidoglycan Fragments by Neisseria gonorrhoeae.
AB  - Neisseria gonorrhoeae gonococcus (GC) is a Gram-negative betaproteobacterium and
      causative agent of the sexually transmitted infection gonorrhea. During growth,
      GC releases lipooligosaccharide (LOS) and peptidoglycan (PG) fragments, which
      contribute significantly to the inflammatory damage observed during human
      infection. In ascending infection of human Fallopian tubes, inflammation leads to
      increased risk of ectopic pregnancy, pelvic inflammatory disease, and sterility.
      Of the PG fragments released by GC, most are disaccharide peptide monomers, and
      of those, 80% have tripeptide stems despite the observation that tetrapeptide
      stems make up 80% of the assembled cell wall. We identified a serine-protease l,d
      carboxypeptidase, NGO1274 (LdcA), as the enzyme responsible for converting cell
      wall tetrapeptide-stem PG to released tripeptide-stem PG. Unlike characterized
      cytoplasmic LdcA homologs in gammaproteobacteria, LdcA in GC is exported to the
      periplasm, and its localization is critical for its activity in modifying PG
      fragments for release. Distinct among other characterized l,d-carboxypeptidases,
      LdcA from GC is also capable of catalyzing the cleavage of specific peptide cross
      bridges (endopeptidase activity). To define the role of ldcA in pathogenesis, we
      demonstrate that ldcA disruption results in both loss of NOD1-dependent NF-kappaB
      activation and decreased NOD2-dependent NF-kappaB activation while not affecting
      Toll-like receptor (TLR) agonist release. Since the human intracellular
      peptidoglycan receptor NOD1 (hNOD1) specifically recognizes PG fragments with a
      terminal meso-DAP rather than d-alanine, we conclude that LdcA is required for GC
      to provoke NOD1-dependent responses in cells of the human host.IMPORTANCE The
      macromolecular meshwork of peptidoglycan serves essential functions in
      determining bacterial cell shape, protecting against osmotic lysis, and defending
      cells from external assaults. The conserved peptidoglycan structure, however, is
      also recognized by eukaryotic pattern recognition receptors, which can trigger
      immune responses against bacteria. Many bacteria can induce an inflammatory
      response through the intracellular peptidoglycan receptor NOD1, but Neisseria
      gonorrhoeae serves as an extreme example, releasing fragments of peptidoglycan
      into the environment during growth that specifically antagonize human NOD1.
      Understanding the peptidoglycan breakdown mechanisms that allow Neisseria to
      promote NOD1 activation, rather than avoiding or suppressing immune detection, is
      critical to understanding the pathogenesis of this increasingly drug-resistant
      organism. We identify a peptidoglycan l,d-carboxypeptidase responsible for
      converting liberated peptidoglycan fragments into the human NOD1 agonist and find
      that the same enzyme has endopeptidase activity on certain peptidoglycan cross
      links, the first described combination of those two activities in a single
      enzyme.

PMID- 29042498
TI  - Capsids and Genomes of Jumbo-Sized Bacteriophages Reveal the Evolutionary Reach
      of the HK97 Fold.
AB  - Large icosahedral viruses that infect bacteria represent an extreme of the
      coevolution of capsids and the genomes they accommodate. One subset of these
      large viruses is the jumbophages, tailed phages with double-stranded DNA genomes
      of at least 200,000 bp. We explored the mechanism leading to increased capsid and
      genome sizes by characterizing structures of several jumbophage capsids and the
      DNA packaged within them. Capsid structures determined for six jumbophages were
      consistent with the canonical phage HK97 fold, and three had capsid geometries
      with novel triangulation numbers (T=25, T=28, and T=52). Packaged DNA
      (chromosome) sizes were larger than the genome sizes, indicating that all
      jumbophages use a head-full DNA packaging mechanism. For two phages (PAU and G),
      the sizes appeared very much larger than their genome length. We used two
      dimensional DNA gel electrophoresis to show that these two DNAs migrated
      abnormally due to base modifications and to allow us to calculate their actual
      chromosome sizes. Our results support a ratchet model of capsid and genome
      coevolution whereby mutations lead to increased capsid volume and allow the
      acquisition of additional genes. Once the added genes and larger capsid are
      established, mutations that restore the smaller size are disfavored.IMPORTANCE A
      large family of viruses share the same fold of the capsid protein as
      bacteriophage HK97, a virus that infects bacteria. Members of this family use
      different numbers of the capsid protein to build capsids of different sizes.
      Here, we examined the structures of extremely large capsids and measured their
      DNA content relative to the sequenced genome lengths, aiming to understand the
      process that increases size. We concluded that mutational changes leading to
      larger capsids become locked in by subsequent changes to the genome organization.

PMID- 29042500
TI  - Immune Regulation of Plasmodium Is Anopheles Species Specific and Infection
      Intensity Dependent.
AB  - Malaria parasite ookinetes must traverse the vector mosquito midgut epithelium to
      transform into sporozoite-producing oocysts. The Anopheles innate immune system
      is a key regulator of this process, thereby determining vector competence and
      disease transmission. The role of Anopheles innate immunity factors as agonists
      or antagonists of malaria parasite infection has been previously determined using
      specific single Anopheles-Plasmodium species combinations. Here we show that the
      two C-type lectins CTL4 and CTLMA2 exert differential agonistic and antagonistic
      regulation of parasite killing in African and South American Anopheles species.
      The C-type lectins regulate both parasite melanization and lysis through
      independent mechanisms, and their implication in parasite melanization is
      dependent on infection intensity rather than mosquito-parasite species
      combination. We show that the leucine-rich repeat protein LRIM1 acts as an
      antagonist on the development of Plasmodium ookinetes and as a regulator of
      oocyst size and sporozoite production in the South American mosquito Anopheles
      albimanus Our findings explain the rare observation of human Plasmodium
      falciparum melanization and define a key factor mediating the poor vector
      competence of Anopheles albimanus for Plasmodium berghei and Plasmodium
      falciparumIMPORTANCE Malaria, one of the world's deadliest diseases, is caused by
      Plasmodium parasites that are vectored to humans by the bite of Anopheles
      mosquitoes. The mosquito's innate immune system is actively engaged in
      suppressing Plasmodium infection. Studies on mosquito immunity revealed multiple
      factors that act as either facilitators or inhibitors of Plasmodium infection,
      but these findings were mostly based on single Anopheles-Plasmodium species
      combinations, not taking into account the diversity of mosquito and parasite
      species. We show that the functions of CTL4 and CTLMA2 have diverged in different
      vector species and can be both agonistic and antagonistic for Plasmodium
      infection. Their protection against parasite melanization in Anopheles gambiae is
      dependent on infection intensity, rather than the mosquito-parasite combination.
      Importantly, we describe for the first time how LRIM1 plays an essential role in
      Plasmodium infection of Anopheles albimanus, suggesting it is a key regulator of
      the poor vector competence of this species.

PMID- 29042499
TI  - Activation of the Listeria monocytogenes Virulence Program by a Reducing
      Environment.
AB  - Upon entry into the host cell cytosol, the facultative intracellular pathogen
      Listeria monocytogenes coordinates the expression of numerous essential virulence
      factors by allosteric binding of glutathione (GSH) to the Crp-Fnr family
      transcriptional regulator PrfA. Here, we report that robust virulence gene
      expression can be recapitulated by growing bacteria in a synthetic medium
      containing GSH or other chemical reducing agents. Bacteria grown under these
      conditions were 45-fold more virulent in an acute murine infection model and
      conferred greater immunity to a subsequent lethal challenge than bacteria grown
      in conventional media. During cultivation in vitro, PrfA activation was
      completely dependent on the intracellular levels of GSH, as a glutathione
      synthase mutant (DeltagshF) was activated by exogenous GSH but not reducing
      agents. PrfA activation was repressed in a synthetic medium supplemented with
      oligopeptides, but the repression was relieved by stimulation of the stringent
      response. These data suggest that cytosolic L. monocytogenes interprets a
      combination of metabolic and redox cues as a signal to initiate robust virulence
      gene expression in vivoIMPORTANCE Intracellular pathogens are responsible for
      much of the worldwide morbidity and mortality from infectious diseases. These
      pathogens have evolved various strategies to proliferate within individual cells
      of the host and avoid the host immune response. Through cellular invasion or the
      use of specialized secretion machinery, all intracellular pathogens must access
      the host cell cytosol to establish their replicative niches. Determining how
      these pathogens sense and respond to the intracellular compartment to establish a
      successful infection is critical to our basic understanding of the pathogenesis
      of each organism and for the rational design of therapeutic interventions.
      Listeria monocytogenes is a model intracellular pathogen with robust in vitro and
      in vivo infection models. Studies of the host-sensing and downstream signaling
      mechanisms evolved by L. monocytogenes often describe themes of pathogenesis that
      are broadly applicable to less tractable pathogens. Here, we describe how
      bacteria use external redox states as a cue to activate virulence.

PMID- 29042501
TI  - Plasmodium falciparum Calcium-Dependent Protein Kinase 2 Is Critical for Male
      Gametocyte Exflagellation but Not Essential for Asexual Proliferation.
AB  - Drug development efforts have focused mostly on the asexual blood stages of the
      malaria parasite Plasmodium falciparum Except for primaquine, which has its own
      limitations, there are no available drugs that target the transmission of the
      parasite to mosquitoes. Therefore, there is a need to validate new parasite
      proteins that can be targeted for blocking transmission. P. falciparum calcium
      dependent protein kinases (PfCDPKs) play critical roles at various stages of the
      parasite life cycle and, importantly, are absent in the human host. These
      features mark them as attractive drug targets. In this study, using CRISPR/Cas9
      we successfully knocked out PfCDPK2 from blood-stage parasites, which was
      previously thought to be an indispensable protein. The growth rate of the PfCDPK2
      knockout (KO) parasites was similar to that of wild-type parasites, confirming
      that PfCDPK2 function is not essential for the asexual proliferation of the
      parasite in vitro The mature male and female gametocytes of PfCDPK2 KO parasites
      become round after induction. However, they fail to infect female Anopheles
      stephensi mosquitoes due to a defect(s) in male gametocyte exflagellation and
      possibly in female gametes.IMPORTANCE Despite reductions in the number of deaths
      it causes, malaria continues to be a leading infectious disease of the developing
      world. For effective control and elimination of malaria, multiple stages of the
      parasite need to be targeted. One such stage includes the transmission of the
      parasite to mosquitoes. Here, we demonstrate the successful knockout of PfCDPK2,
      which was previously thought to be indispensable for parasite growth in red blood
      cells. The PfCDPK2 KO parasites are incapable of establishing an infection in
      mosquitoes. Therefore, our study suggests that targeting PfCDPK2 may be a good
      strategy to control malaria transmission in countries with high transmission.
      Moreover, molecular understanding of the signaling pathway of PfCDPK2 may provide
      additional targets for malaria control.

PMID- 29042503
TI  - Erratum for Hagan et al., "Petrobactin Is Exported from Bacillus anthracis by the
      RND-Type Exporter ApeX".

PMID- 29042502
TI  - Lipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic
      Epithelial Proliferation-to-Differentiation Balance.
AB  - We identified a crypt-specific core microbiota (CSCM) dominated by strictly
      aerobic, nonfermentative bacteria in murine cecal and proximal colonic (PC)
      crypts and hypothesized that, among its possible functions, it may affect
      epithelial regeneration. In the present work, we isolated representative CSCM
      strains using selective media based upon our initial 16S rRNA-based molecular
      identification (i.e., Acinetobacter, Delftia, and Stenotrophomonas). Their
      tropism for the crypt was confirmed, and their influence on epithelial
      regeneration was demonstrated in vivo by monocolonization of germfree mice. We
      also showed that lipopolysaccharide (LPS), through its endotoxin activity, was
      the dominant bacterial agonist controlling proliferation. The relevant molecular
      mechanisms were analyzed using colonic crypt-derived organoids exposed to
      bacterial sonicates or highly purified LPS as agonists. We identified a Toll-like
      receptor 4 (TLR4)-dependent program affecting crypts at different stages of
      epithelial differentiation. LPS played a dual role: it repressed cell
      proliferation through RIPK3-mediated necroptosis of stem cells and cells of the
      transit-amplifying compartment and concurrently enhanced cell differentiation,
      particularly the goblet cell lineage.IMPORTANCE The LPS from crypt-specific core
      microbiota controls intestinal epithelium proliferation through necroptosis of
      stem cells and enhances cell differentiation, mainly the goblet cell lineage.

PMID- 29042504
TI  - Unintended Laboratory-Driven Evolution Reveals Genetic Requirements for Biofilm
      Formation by Desulfovibrio vulgaris Hildenborough.
AB  - Biofilms of sulfate-reducing bacteria (SRB) are of particular interest as members
      of this group are culprits in corrosion of industrial metal and concrete
      pipelines as well as being key players in subsurface metal cycling. Yet the
      mechanism of biofilm formation by these bacteria has not been determined. Here we
      show that two supposedly identical wild-type cultures of the SRB Desulfovibrio
      vulgaris Hildenborough maintained in different laboratories have diverged in
      biofilm formation. From genome resequencing and subsequent mutant analyses, we
      discovered that a single nucleotide change within DVU1017, the ABC transporter of
      a type I secretion system (T1SS), was sufficient to eliminate biofilm formation
      in D. vulgaris Hildenborough. Two T1SS cargo proteins were identified as likely
      biofilm structural proteins, and the presence of at least one (with either being
      sufficient) was shown to be required for biofilm formation. Antibodies specific
      to these biofilm structural proteins confirmed that DVU1017, and thus the T1SS,
      is essential for localization of these adhesion proteins on the cell surface. We
      propose that DVU1017 is a member of the lapB category of microbial surface
      proteins because of its phenotypic similarity to the adhesin export system
      described for biofilm formation in the environmental pseudomonads. These findings
      have led to the identification of two functions required for biofilm formation in
      D. vulgaris Hildenborough and focus attention on the importance of monitoring
      laboratory-driven evolution, as phenotypes as fundamental as biofilm formation
      can be altered.IMPORTANCE The growth of bacteria attached to a surface (i.e.,
      biofilm), specifically biofilms of sulfate-reducing bacteria, has a profound
      impact on the economy of developed nations due to steel and concrete corrosion in
      industrial pipelines and processing facilities. Furthermore, the presence of
      sulfate-reducing bacteria in oil wells causes oil souring from sulfide
      production, resulting in product loss, a health hazard to workers, and ultimately
      abandonment of wells. Identification of the required genes is a critical step for
      determining the mechanism of biofilm formation by sulfate reducers. Here, the
      transporter by which putative biofilm structural proteins are exported from
      sulfate-reducing Desulfovibrio vulgaris Hildenborough cells was discovered, and a
      single nucleotide change within the gene coding for this transporter was found to
      be sufficient to completely stop formation of biofilm.

PMID- 29042505
TI  - Binding synergy as an essential step for tRNA editing and modification enzyme
      codependence in Trypanosoma brucei.
AB  - Transfer RNAs acquire a variety of naturally occurring chemical modifications
      during their maturation; these fine-tune their structure and decoding properties
      in a manner critical for protein synthesis. We recently reported that in the
      eukaryotic parasite, Trypanosoma brucei, a methylation and deamination event are
      unexpectedly interconnected, whereby the tRNA adenosine deaminase (TbADAT2/3) and
      the 3-methylcytosine methyltransferase (TbTrm140) strictly rely on each other for
      activity, leading to formation of m3C and m3U at position 32 in several tRNAs.
      Still however, it is not clear why these two enzymes, which work independently in
      other systems, are strictly codependent in T. brucei Here, we show that these
      enzymes exhibit binding synergism, or a mutual increase in binding affinity, that
      is more than the sum of the parts, when added together in a reaction. Although
      these enzymes interact directly with each other, tRNA binding assays using enzyme
      variants mutated in critical binding and catalytic sites indicate that the
      observed binding synergy stems from contributions from tRNA-binding domains
      distal to their active sites. These results provide a rationale for the known
      interactions of these proteins, while also speaking to the modulation of
      substrate specificity between seemingly unrelated enzymes. This information
      should be of value in furthering our understanding of how tRNA modification
      enzymes act together to regulate gene expression at the post-transcriptional
      level and provide a basis for the interdependence of such activities.

PMID- 29042506
TI  - Non-Watson-Crick RNA synthesis suited to origin functions.
AB  - A templated RNA synthesis is characterized in which G5'pp5'G accelerates
      synthesis of A5'pp5'A from pA and chemically activated ImpA precursors. Similar
      acceleration is not observable in the presence of UppU, CppC, AppG, AppA, or pG
      alone. Thus, it seems likely that AppA is templated by GppG via a form or forms
      of G:A base-pairing. AppA also appears, more slowly, via a previously known
      untemplated second-order chemical route. Such AppA synthesis requires only
      ordinary near-neutral solutions containing monovalent and divalent salts, and
      rates are only slightly sensitive to variation in pH. Templated synthesis rates
      are first order in pA, ImpA, and template GppG; thus third order overall.
      Therefore, this reaction resembles cross-templating of AppA on poly(U), but is
      notably slower and less sensitive to temperature. Viewing AppA as a coenzyme
      analog, GppG templating provides a simpler molecular route, termed para
      templating, to encoded chemical functions. Para-templating can also arise from a
      single, localized nucleobase geosynthetic event which yields purines. It requires
      only a single backbone-forming chemistry. Thus it may have appeared earlier and
      served as evolutionary precursor for more complex forms of encoded genetic
      expression.

PMID- 29042507
TI  - Selection of functional 2A sequences within foot-and-mouth disease virus;
      requirements for the NPGP motif with a distinct codon bias.
AB  - Foot-and-mouth disease virus (FMDV) has a positive-sense ssRNA genome including a
      single, large, open reading frame. Splitting of the encoded polyprotein at the
      2A/2B junction is mediated by the 2A peptide (18 residues long), which induces a
      nonproteolytic, cotranslational "cleavage" at its own C terminus. A conserved
      feature among variants of 2A is the C-terminal motif N16P17G18/P19, where P19 is
      the first residue of 2B. It has been shown previously that certain amino acid
      substitutions can be tolerated at residues E14, S15, and N16 within the 2A
      sequence of infectious FMDVs, but no variants at residues P17, G18, or P19 have
      been identified. In this study, using highly degenerate primers, we analyzed if
      any other residues can be present at each position of the NPG/P motif within
      infectious FMDV. No alternative forms of this motif were found to be encoded by
      rescued FMDVs after two, three, or four passages. However, surprisingly, a clear
      codon preference for the wt nucleotide sequence encoding the NPGP motif within
      these viruses was observed. Indeed, the codons selected to code for P17 and P19
      within this motif were distinct; thus the synonymous codons are not equivalent.

PMID- 29042508
TI  - Just-in-time simulation-based training.

PMID- 29042509
TI  - Properties of real metallic surfaces: Effects of density functional semilocality
      and van der Waals nonlocality.
AB  - We have computed the surface energies, work functions, and interlayer surface
      relaxations of clean (111), (100), and (110) surfaces of Al, Cu, Ru, Rh, Pd, Ag,
      Pt, and Au. We interpret the surface energy from liquid metal measurements as the
      mean of the solid-state surface energies over these three lowest-index crystal
      faces. We compare experimental (and random phase approximation) reference values
      to those of a family of nonempirical semilocal density functionals, from the
      basic local density approximation (LDA) to our most advanced general purpose meta
      generalized gradient approximation, strongly constrained and appropriately normed
      (SCAN). The closest agreement is achieved by the simplest density functional LDA,
      and by the most sophisticated one, SCAN+rVV10 (Vydrov-Van Voorhis 2010). The long
      range van der Waals interaction, incorporated through rVV10, increases the
      surface energies by about 10%, and increases the work functions by about 3%. LDA
      works for metal surfaces through two known error cancellations. The Perdew-Burke
      Ernzerhof generalized gradient approximation tends to underestimate both surface
      energies (by about 24%) and work functions (by about 4%), yielding the least
      accurate results. The amount by which a functional underestimates these surface
      properties correlates with the extent to which it neglects van der Waals
      attraction at intermediate and long range. Qualitative arguments are given for
      the signs of the van der Waals contributions to the surface energy and work
      function. A standard expression for the work function in Kohn-Sham (KS) theory is
      shown to be valid in generalized KS theory. Interlayer relaxations from different
      functionals are in reasonable agreement with one another, and usually with
      experiment.

PMID- 29042510
TI  - The misleading narrative of the canonical faculty productivity trajectory.
AB  - A scientist may publish tens or hundreds of papers over a career, but these
      contributions are not evenly spaced in time. Sixty years of studies on career
      productivity patterns in a variety of fields suggest an intuitive and universal
      pattern: Productivity tends to rise rapidly to an early peak and then gradually
      declines. Here, we test the universality of this conventional narrative by
      analyzing the structures of individual faculty productivity time series,
      constructed from over 200,000 publications and matched with hiring data for 2,453
      tenure-track faculty in all 205 PhD-granting computer science departments in the
      United States and Canada. Unlike prior studies, which considered only some
      faculty or some institutions, or lacked common career reference points, here we
      combine a large bibliographic dataset with comprehensive information on career
      transitions that covers an entire field of study. We show that the conventional
      narrative confidently describes only one-fifth of faculty, regardless of
      department prestige or researcher gender, and the remaining four-fifths of
      faculty exhibit a rich diversity of productivity patterns. To explain this
      diversity, we introduce a simple model of productivity trajectories and explore
      correlations between its parameters and researcher covariates, showing that
      departmental prestige predicts overall individual productivity and the timing of
      the transition from first- to last-author publications. These results demonstrate
      the unpredictability of productivity over time and open the door for new efforts
      to understand how environmental and individual factors shape scientific
      productivity.

PMID- 29042511
TI  - Dynamics and unsteady morphologies at ice interfaces driven by D2O-H2O exchange.
AB  - The growth dynamics of D2O ice in liquid H2O in a microfluidic device were
      investigated between the melting points of D2O ice (3.8  degrees C) and H2O ice
      (0  degrees C). As the temperature was decreased at rates between 0.002  degrees
      C/s and 0.1  degrees C/s, the ice front advanced but retreated immediately upon
      cessation of cooling, regardless of the temperature. This is a consequence of the
      competition between diffusion of H2O into the D2O ice, which favors melting of
      the interface, and the driving force for growth supplied by cooling. Raman
      microscopy tracked H/D exchange across the solid H2O-solid D2O interface, with
      diffusion coefficients consistent with transport of intact H2O molecules at the
      D2O ice interface. At fixed temperatures below 3  degrees C, the D2O ice front
      melted continuously, but at temperatures near 0  degrees C a scalloped interface
      morphology appeared with convex and concave sections that cycled between growth
      and retreat. This behavior, not observed for D2O ice in contact with D2O liquid
      or H2O ice in contact with H2O liquid, reflects a complex set of cooperative
      phenomena, including H/D exchange across the solid-liquid interface, latent heat
      exchange, local thermal gradients, and the Gibbs-Thomson effect on the melting
      points of the convex and concave features.

PMID- 29042512
TI  - In vitro reconstitution of T cell receptor-mediated segregation of the CD45
      phosphatase.
AB  - T cell signaling initiates upon the binding of peptide-loaded MHC (pMHC) on an
      antigen-presenting cell to the T cell receptor (TCR) on a T cell. TCR
      phosphorylation in response to pMHC binding is accompanied by segregation of the
      transmembrane phosphatase CD45 away from TCR-pMHC complexes. The kinetic
      segregation hypothesis proposes that CD45 exclusion shifts the local kinase
      phosphatase balance to favor TCR phosphorylation. Spatial partitioning may arise
      from the size difference between the large CD45 extracellular domain and the
      smaller TCR-pMHC complex, although parsing potential contributions of
      extracellular protein size, actin activity, and lipid domains is difficult in
      living cells. Here, we reconstitute segregation of CD45 from bound receptor
      ligand pairs using purified proteins on model membranes. Using a model receptor
      ligand pair (FRB-FKBP), we first test physical and computational predictions for
      protein organization at membrane interfaces. We then show that the TCR-pMHC
      interaction causes partial exclusion of CD45. Comparing two developmentally
      regulated isoforms of CD45, the larger RABC variant is excluded more rapidly and
      efficiently (~50%) than the smaller R0 isoform (~20%), suggesting that CD45
      isotypes could regulate signaling thresholds in different T cell subtypes.
      Similar to the sensitivity of T cell signaling, TCR-pMHC interactions with Kds of
      <=15 uM were needed to exclude CD45. We further show that the coreceptor PD-1
      with its ligand PD-L1, immunotherapy targets that inhibit T cell signaling, also
      exclude CD45. These results demonstrate that the binding energies of
      physiological receptor-ligand pairs on the T cell are sufficient to create
      spatial organization at membrane-membrane interfaces.

PMID- 29042513
TI  - Distress and rumor exposure on social media during a campus lockdown.
AB  - During crisis events, people often seek out event-related information to stay
      informed of what is happening. However, when information from official channels
      is lacking or disseminated irregularly, people may be at risk for exposure to
      rumors that fill the information void. We studied information-seeking during a
      university lockdown following an active-shooter event. In study 1, students in
      the lockdown (n = 3,890) completed anonymous surveys 1 week later. Those who
      indicated receiving conflicting information about the lockdown reported greater
      acute stress [standardized regression coefficient (b) = 0.07; SE = 0.01; 95%
      confidence interval (CI), 0.04, 0.10]. Additionally, those who reported direct
      contact with close others via text message (or phone) and used Twitter for
      critical updates during the lockdown were exposed to more conflicting
      information. Higher acute stress was reported by heavy social media users who
      trusted social media for critical updates (b = 0.06, SE = 0.01; 95% CI, 0.03,
      0.10). In study 2, we employed a big data approach to explore the time course of
      rumor transmission across 5 hours surrounding the lockdown within a subset of the
      university's Twitter followers. We also examined the patterning of distress in
      the hours during the lockdown as rumors about what was happening (e.g., presence
      of multiple shooters) spread among Twitter users. During periods without updates
      from official channels, rumors and distress increased. Results highlight the
      importance of releasing substantive updates at regular intervals during a crisis
      event and monitoring social media for rumors to mitigate rumor exposure and
      distress.

PMID- 29042514
TI  - Neuron-specific methylome analysis reveals epigenetic regulation and tau-related
      dysfunction of BRCA1 in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by
      pathology of accumulated amyloid beta (Abeta) and phosphorylated tau proteins in
      the brain. Postmortem degradation and cellular complexity within the brain have
      limited approaches to molecularly define the causal relationship between
      pathological features and neuronal dysfunction in AD. To overcome these
      limitations, we analyzed the neuron-specific DNA methylome of postmortem brain
      samples from AD patients, which allowed differentially hypomethylated region of
      the BRCA1 promoter to be identified. Expression of BRCA1 was significantly up
      regulated in AD brains, consistent with its hypomethylation. BRCA1 protein levels
      were also elevated in response to DNA damage induced by Abeta. BRCA1 became
      mislocalized to the cytoplasm and highly insoluble in a tau-dependent manner,
      resulting in DNA fragmentation in both in vitro cellular and in vivo mouse
      models. BRCA1 dysfunction under Abeta burden is consistent with concomitant
      deterioration of genomic integrity and synaptic plasticity. The Brca1 promoter
      region of AD model mice brain was similarly hypomethylated, indicating an
      epigenetic mechanism underlying BRCA1 regulation in AD. Our results suggest
      deterioration of DNA integrity as a central contributing factor in AD
      pathogenesis. Moreover, these data demonstrate the technical feasibility of using
      neuron-specific DNA methylome analysis to facilitate discovery of etiological
      candidates in sporadic neurodegenerative diseases.

PMID- 29042515
TI  - Structural basis for regulation of the nucleo-cytoplasmic distribution of Bag6 by
      TRC35.
AB  - The metazoan protein BCL2-associated athanogene cochaperone 6 (Bag6) forms a
      hetero-trimeric complex with ubiquitin-like 4A and transmembrane domain
      recognition complex 35 (TRC35). This Bag6 complex is involved in tail-anchored
      protein targeting and various protein quality-control pathways in the cytosol as
      well as regulating transcription and histone methylation in the nucleus. Here we
      present a crystal structure of Bag6 and its cytoplasmic retention factor TRC35,
      revealing that TRC35 is remarkably conserved throughout the opisthokont lineage
      except at the C-terminal Bag6-binding groove, which evolved to accommodate Bag6,
      a unique metazoan factor. While TRC35 and its fungal homolog, guided entry of
      tail-anchored protein 4 (Get4), utilize a conserved hydrophobic patch to bind
      their respective partners, Bag6 wraps around TRC35 on the opposite face relative
      to the Get4-5 interface. We further demonstrate that TRC35 binding is critical
      not only for occluding the Bag6 nuclear localization sequence from karyopherin
      alpha to retain Bag6 in the cytosol but also for preventing TRC35 from succumbing
      to RNF126-mediated ubiquitylation and degradation. The results provide a
      mechanism for regulation of Bag6 nuclear localization and the functional
      integrity of the Bag6 complex in the cytosol.

PMID- 29042516
TI  - Across the tree of life, radiation resistance is governed by antioxidant Mn2+,
      gauged by paramagnetic resonance.
AB  - Despite concerted functional genomic efforts to understand the complex phenotype
      of ionizing radiation (IR) resistance, a genome sequence cannot predict whether a
      cell is IR-resistant or not. Instead, we report that absorption-display electron
      paramagnetic resonance (EPR) spectroscopy of nonirradiated cells is highly
      diagnostic of IR survival and repair efficiency of DNA double-strand breaks
      (DSBs) caused by exposure to gamma radiation across archaea, bacteria, and
      eukaryotes, including fungi and human cells. IR-resistant cells, which are
      efficient at DSB repair, contain a high cellular content of manganous ions (Mn2+)
      in high-symmetry (H) antioxidant complexes with small metabolites (e.g.,
      orthophosphate, peptides), which exhibit narrow EPR signals (small zero-field
      splitting). In contrast, Mn2+ ions in IR-sensitive cells, which are inefficient
      at DSB repair, exist largely as low-symmetry (L) complexes with substantially
      broadened spectra seen with enzymes and strongly chelating ligands. The fraction
      of cellular Mn2+ present as H-complexes (H-Mn2+), as measured by EPR of live,
      nonirradiated Mn-replete cells, is now the strongest known gauge of biological IR
      resistance between and within organisms representing all three domains of life:
      Antioxidant H-Mn2+ complexes, not antioxidant enzymes (e.g., Mn superoxide
      dismutase), govern IR survival. As the pool of intracellular metabolites needed
      to form H-Mn2+ complexes depends on the nutritional status of the cell, we
      conclude that IR resistance is predominantly a metabolic phenomenon. In a cross
      kingdom analysis, the vast differences in taxonomic classification, genome size,
      and radioresistance between cell types studied here support that IR resistance is
      not controlled by the repertoire of DNA repair and antioxidant enzymes.

PMID- 29042517
TI  - Control of growth and gut maturation by HoxD genes and the associated lncRNA
      Haglr.
AB  - During embryonic development, Hox genes participate in the building of a
      functional digestive system in metazoans, and genetic conditions involving these
      genes lead to important, sometimes lethal, growth retardation. Recently, this
      phenotype was obtained after deletion of Haglr, the Hoxd antisense growth
      associated long noncoding RNA (lncRNA) located between Hoxd1 and Hoxd3 In this
      study, we have analyzed the function of Hoxd genes in delayed growth trajectories
      by looking at several nested targeted deficiencies of the mouse HoxD cluster.
      Mutant pups were severely stunted during the suckling period, but many recovered
      after weaning. After comparing seven distinct HoxD alleles, including CRISPR/Cas9
      deletions involving Haglr, we identified Hoxd3 as the critical component for the
      gut to maintain milk-digestive competence. This essential function could be
      abrogated by the dominant-negative effect of HOXD10 as shown by a genetic rescue
      approach, thus further illustrating the importance of posterior prevalence in Hox
      gene function. A role for the lncRNA Haglr in the control of postnatal growth
      could not be corroborated.

PMID- 29042518
TI  - Evolutionary genomics of grape (Vitis vinifera ssp. vinifera) domestication.
AB  - We gathered genomic data from grapes (Vitis vinifera ssp. vinifera), a clonally
      propagated perennial crop, to address three ongoing mysteries about plant
      domestication. The first is the duration of domestication; archaeological
      evidence suggests that domestication occurs over millennia, but genetic evidence
      indicates that it can occur rapidly. We estimated that our wild and cultivated
      grape samples diverged ~22,000 years ago and that the cultivated lineage
      experienced a steady decline in population size (Ne ) thereafter. The long
      decline may reflect low-intensity management by humans before domestication. The
      second mystery is the identification of genes that contribute to domestication
      phenotypes. In cultivated grapes, we identified candidate-selected genes that
      function in sugar metabolism, flower development, and stress responses. In
      contrast, candidate-selected genes in the wild sample were limited to abiotic and
      biotic stress responses. A genomic region of high divergence corresponded to the
      sex determination region and included a candidate male sterility factor and
      additional genes with sex-specific expression. The third mystery concerns the
      cost of domestication. Annual crops accumulate putatively deleterious variants,
      in part due to strong domestication bottlenecks. The domestication of perennial
      crops differs from that of annuals in several ways, including the intensity of
      bottlenecks, and it is not yet clear if they accumulate deleterious variants. We
      found that grape accessions contained 5.2% more deleterious variants than wild
      individuals, and these were more often in a heterozygous state. Using forward
      simulations, we confirm that clonal propagation leads to the accumulation of
      recessive deleterious mutations but without decreasing fitness.

PMID- 29042519
TI  - Balanced excitation and inhibition are required for high-capacity, noise-robust
      neuronal selectivity.
AB  - Neurons and networks in the cerebral cortex must operate reliably despite
      multiple sources of noise. To evaluate the impact of both input and output noise,
      we determine the robustness of single-neuron stimulus selective responses, as
      well as the robustness of attractor states of networks of neurons performing
      memory tasks. We find that robustness to output noise requires synaptic
      connections to be in a balanced regime in which excitation and inhibition are
      strong and largely cancel each other. We evaluate the conditions required for
      this regime to exist and determine the properties of networks operating within
      it. A plausible synaptic plasticity rule for learning that balances weight
      configurations is presented. Our theory predicts an optimal ratio of the number
      of excitatory and inhibitory synapses for maximizing the encoding capacity of
      balanced networks for given statistics of afferent activations. Previous work has
      shown that balanced networks amplify spatiotemporal variability and account for
      observed asynchronous irregular states. Here we present a distinct type of
      balanced network that amplifies small changes in the impinging signals and
      emerges automatically from learning to perform neuronal and network functions
      robustly.

PMID- 29042520
TI  - [Epilepsy and Driving].
AB  - In Japan, the Road Traffic Act was amended in 2013, and the revision was enacted
      in 2014. This revision includes new rules such as the requirement that a driver
      declare medical conditions on licensing, with a penalty for false statements.
      There is also a new voluntary notification system that enables doctors to report
      unlawful drivers. At the same time, the new Criminal Law Act was enacted. This
      act provides a penalty for causing death or injury to other persons by driving
      under the influence of specific drugs or diseases, including epilepsy. There is a
      prison term of up to 15 years for this violation. These new laws are the result
      of several tragic motor vehicle accidents caused by patients with epilepsy who
      were unfit to drive, and severe punishments are involved. Japan still requires a
      longer seizure-free period for licensing of patients with epilepsy (2 or 5
      years), as opposed to the shorter periods required by other developed countries
      (US, 3 to 12 months; EU, 12 months). It is debatable whether harsh punishments
      are more effective in reducing accidents. Further reevaluation and discussion are
      needed on this issue because a restrictive policy for handicapped persons should
      be based on scientific evidence and should not be biased by prejudice and
      discrimination.

PMID- 29042521
TI  - [Transition of Children with Epilepsy to Adult Care: Current Status and
      Challenge].
AB  - Thirty percent of the patients consulting a pediatric neurologist have already
      reached adulthood as patients and their families do not like transfer to the
      adult clinics; moreover, there are no suitable clinics. Pediatric neurologists
      find it difficult to examine adult patients with childhood-onset epilepsy as they
      are unfamiliar with the psychiatric and psychological symptoms manifested in
      adulthood, and the common diseases of adulthood. On the other hand, adult
      neurologists have difficulty obtaining a complete picture of the patient's
      clinical history since childhood, and are unfamiliar with childhood-specific
      epilepsy syndrome. When it comes to transition, the patient's decision should be
      prioritized. Transition should be patient-centered, with cornerstones of
      flexibility, responsiveness, continuity, comprehensiveness, and coordination. For
      successful transition to occur, there must be psychosocial support, patient
      education, better medical system organization with inclusion of a transition
      process, such as transition clinic, increased number of epilepsy-specialized
      physicians/nurses, and resources such as checklists and programs to aid in
      transition.

PMID- 29042522
TI  - [Surgical Pathology of Adulthood Epilepsy].
AB  - Epilepsy may be the consequence of a wide range of disorders affecting the brain,
      including tumors and non-neoplastic lesions. A broad spectrum of structural brain
      lesions can be observed in epileptogenic brain tissue specimens surgically
      resected from patients with drug-resistant focal epilepsies. These include
      hippocampal sclerosis (HS), low-grade epilepsy-associated neuroepithelial tumors
      (LEAT), malformations of cortical development (MCD), vascular malformations, dual
      pathology, glial scar, and encephalitis, as well as no lesion. HS, LEAT, and MCD
      constitute over 75% of all surgical pathologies of epilepsy. International
      consensus histological classifications of HS and focal cortical dysplasia (FCD)
      have been proposed by the International League Against Epilepsy (ILAE), based on
      agreement on the importance of defining a histopathological classification system
      that has a reliable clinicopathological correlation. These ILAE classifications
      are likely to facilitate future clinicopathological studies. The validity and
      usefulness of the ILAE classifications should be further evaluated for future
      revision for clinicopathologically meaningful classification with better
      interobserver agreement, particularly for FCD types I and III. Although it is
      still an emerging field of neuropathology, surgical pathology of epilepsy will
      likely play an important role in unraveling the pathogenesis and epileptogenesis
      of structural brain lesions, thereby contributing to the future precision
      medicine.

PMID- 29042523
TI  - [Current Status of Epilepsy Surgery in Adults].
AB  - Epilepsy surgery is an effective way to control seizures in patients with
      refractory epilepsy, even in patients in whom drug therapy has not resulted in
      adequate seizure control. Many studies support the efficacy and safety of
      resective and non-resective surgeries for the treatment of refractory epilepsy in
      appropriately selected individuals. However, it is sometimes argued that epilepsy
      surgery is underutilized despite the evidence and guidelines supporting its use.
      Among the causes cited for underutilization of this treatment are numerous
      barriers to epilepsy surgery. Further strategies are needed to increase access to
      surgery and to improve communication about the effectiveness of this potentially
      life-changing procedure. In addition, epilepsy surgery is only one part of the
      multimodal treatment of refractory epilepsy. A comprehensive approach is required
      to address the medical, surgical, psychosocial, rehabilitation and moral needs of
      patients with epilepsy in order to improve their quality of life.

PMID- 29042524
TI  - [Autoimmune and Epilepsy].
AB  - The recent discovery of autoimmune antibodies to the neuronal cell surface
      membrane and extra- or intra-cellular proteins, such as NMDAR and LGI1, shed
      light on a proposed new etiology of epilepsy, namely, "autoimmune epilepsy". A
      large part of this entity most likely belongs to a forme fruste of autoimmune
      (limbic) encephalitis. Seizures are usually subacute in onset and refractory to
      antiepileptic medications. Patients occasionally manifest multiple seizure
      semiologies, such as autonomic or faciobrachial dystonic seizures. They may
      develop other symptoms of autoimmune encephalitis to variable degrees. Clinical
      diagnosis of autoimmune epilepsy should be considered even before the results of
      antibody testing, when objective evidence of CNS inflammation, such as abnormal
      MRI (amygdala/hippocampal enlargement), FDG-PET (hypermetabolism), EEG
      (bitemporal spikes or subclinical seizure patterns) and/or CSF findings, are
      present. Early intensive immunotherapy could cure seizures and prevent the full
      blown clinical manifestation of encephalitis. Some patients present with
      relatively mild clinical symptoms and/or MRI findings, and can have a smoldering
      course lasting years. Establishment of the biomarkers of the ongoing CNS
      inflammation, especially for the smoldering and the suspected autoantibody
      negative cases, is warranted for tailored immunotherapy for both the subacute and
      chronic phases of the disease.

PMID- 29042525
TI  - [Characteristics of Geriatric Epilepsy Can Include Dementia].
AB  - Japan has become a "super-aged" society, in which more than 20% of the population
      is over the age of 65 years. As the incidence rates of both dementia and epilepsy
      are high in elderly individuals, the prevalence rates of dementia and epilepsy
      have both increased in recent years. Dementia and epilepsy are often
      characterized by ambiguous symptoms, with numerous concomitant symptoms observed
      in these patients. Moreover, many reports indicate that the forgetfulness
      observed in dementia patients was actually due to the occurrence of epileptic
      seizures. Because Japan is currently a super-aged society, it is important to
      understand the characteristics of and relationships between dementia and
      epilepsy.

PMID- 29042526
TI  - [Differential Diagnosis of Immune-Mediated Encephalopathies: "Neurological
      Symptoms of Diffuse Brain Damage": A New Concept].
AB  - In recent years, incidence of autoimmune encephalopathies has increased. The
      diagnosis of the severe form of autoimmune encephalopathy is not difficult;
      however, milder forms can be misdiagnosed as general encephalopathies. We often
      treat Hashimoto's encephalopathy, which has diverse clinical symptoms and is
      often misdiagnosed as a psychosomatic disease. We have found that the
      neurological findings and symptoms of patients with Hashimoto's encephalopathy
      are similar to those of psychogenic diseases, such as giveway weakness and
      atypical sensory disorder. To understand the mechanism underlying these symptoms,
      we propose a new concept: neurological symptoms of diffuse brain damage. This
      theory is based on the premise that etiologically, symptoms observed were caused
      by diffuse, spotty, and shaded brain damage due to autoimmune encephalopathies.
      We also found similar neurological conditions in patients with anti-ganglionic
      acetylcholine receptor antibody-related encephalopathy, encephalopathies that
      developed after injection of the cervical cancer vaccine, and encephalopathies
      associated with Stiff person syndrome. In conclusion, the clinical features of
      autoimmune encephalopathy include the "neurological symptoms of diffuse brain
      damage" as well as the presence of antibodies. We could diagnose autoimmune
      encephalopathy more easily, using this new diagnostic concept.

PMID- 29042527
TI  - [Biomarkers for Mood Disorders and a Novel Antidepressant (R)-ketamine].
AB  - Depression is often misdiagnosed as major depressive disorder in patients with
      bipolar disorder. Therapeutic drugs for these two disorders are quite different,
      but the anesthetic ketamine shows fast-acting antidepressant effects in treatment
      resistant patients with these disorders. Here, we discuss biomarkers for both
      disorders, recent findings regarding ketamine, and predictable biomarkers for
      ketamine's antidepressant actions.

PMID- 29042528
TI  - [A Case of Ruptured Anterior Communicating Artery Aneurysm with Visual Field
      Defects and Deteriorating to Severe Vision Loss].
AB  - Although Terson's syndrome is a well-known cause of vision loss due to
      intracerebral aneurysm rupture, optic nerve neuropathy can also occur because of
      other causes. Here, we report such a case, i.e., a ruptured anterior
      communicating artery aneurysm accompanied by vision loss and visual field
      disturbances due to a cause other than Terson's syndrome. A 47-year-old man
      presented with right superior altitudinal hemianopia. Computed tomography (CT)
      showed subarachnoid hemorrhage (SAH), and three-dimensional CT angiography
      revealed an anterior communicating artery aneurysm. Coil embolization was
      performed. Right visual acuity degenerated to blindness in the acute stage. MRI
      performed on day 7 post-admission revealed that the aneurysm had swollen and made
      contact with the right optic disk. On the basis of the patient's clinical course,
      we believe that the deterioration in his visual acuity could have been due to
      ischemic optic neuropathy (ION) resulting from SAH, and the subsequent edema and
      poor blood perfusion may be attributed to spasm. In cases of visual disturbance
      associated with SAH, as in our case, it is important to perform MRI to evaluate
      the damage or risk to the optic nerve as soon as possible. (Received December 26,
      2016; Accepted June 9, 2017; Published October 1, 2017).

PMID- 29042529
TI  - Value of Preoperative Indocyanine Green Clearance Test for Predicting Post
      Hepatectomy Liver Failure in Noncirrhotic Patients.
AB  - BACKGROUND Liver failure is the most feared complication following hepatectomy.
      Post-hepatectomy liver failure (PHLF) is closely related to the remnant liver
      volume, and functional reserve. There are several methods for predicting PHLF
      prior to liver resection. The indocyanine green (ICG) clearance test was
      popularized in patients with hepatocellular cancer (HCC). We aim to demonstrate
      the value of preoperative ICG clearance measurement via pulse spectrophotometer
      (LIMON(r)) in prediction of PHLF in noncirrhotic patients prior to liver
      resection. MATERIAL AND METHODS Fifty-three noncirrhotic patients who underwent
      liver resection due to different pathologies were included. Retrospectively
      collected clinical data, including the preoperative ICG clearance measurements
      and remnant liver volumes of the patients, were statistically evaluated according
      to the PHLF criteria of the International Study Group of Liver Surgery. RESULTS
      Four (7.5%) patients with PHLF were observed. There was no significant difference
      between PHLF and non-PHLF groups regarding ICG clearance measurements with cut
      off values of 5% and 9.5%. CONCLUSIONS The ICG clearance test does not satisfy
      our expectations in noncirrhotic patients in predicting PHLF. We believe that the
      ICG clearance test should be reserved for patients with cirrhosis and/or HCC.
      This test could be an option for noncirrhotic patients with chronic active
      hepatitis, advanced-grade fatty livers, or for patients who received long-term
      preoperative chemotherapy, and also for patients who underwent single or multiple
      sessions of TACE or TARE prior to liver resection. If the routine selection
      criteria have been fulfilled, there is no further need to perform the ICG
      clearance test for living liver donors.

PMID- 29042530
TI  - Hypereosinophilia Secondary to Disseminated Paracoccidioidomycosis.
AB  - BACKGROUND Paracoccidioidomycosis is an endemic mycosis in Central and South
      America caused by the thermally dimorphic fungus Paracoccidioides brasiliensis.
      Despite its self-limited course and usually asymptomatic infection, some patients
      may present with a systemic illness mimicking multiple conditions and thus
      question the general state of their immune system. CASE REPORT A 28-year-old male
      presented to the hospital with fever, dry cough, and non-pruritic rash with no
      characteristic distribution for the past 10 days. Past medical history revealed
      that the patient had worked as a farmer three years ago, had abused cocaine paste
      over the same period, and also had in the last month presented to the hospital
      for acute appendicitis. Initial laboratory tests revealed hypereosinophilia
      greater than 10,000 eosinophils/mL. Infection of P. brasiliensis was confirmed by
      lymph node, skin, and colonoscopy biopsies. After treatment with itraconazole,
      the patient's eosinophil count returned to normal and his symptoms resolved.
      CONCLUSIONS Paracoccidioidomycosis may present as a systemic illness with only
      marked eosinophilia on initial diagnostic tests. Furthermore, in our patient's
      case, the high degree of eosinophilia may have contributed towards the patient's
      appendicitis in the weeks preceding the subacute infection. It is possible that
      the patient's history of working at a farm and abusing cocaine paste may have
      contributed to the initial colonization by the fungus.

PMID- 29042531
TI  - Extrafollicular CD4+ T-B interactions are sufficient for inducing autoimmune-like
      chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (cGVHD) is an autoimmune-like syndrome mediated
      by pathogenic CD4+ T and B cells, but the function of extrafollicular and
      germinal center CD4+ T and B interactions in cGVHD pathogenesis remains largely
      unknown. Here we show that extrafollicular CD4+ T and B interactions are
      sufficient for inducing cGVHD, while germinal center formation is dispensable.
      The pathogenesis of cGVHD is associated with the expansion of extrafollicular
      CD44hiCD62loPSGL-1loCD4+ (PSGL-1loCD4+) T cells. These cells express high levels
      of ICOS, and the blockade of ICOS/ICOSL interaction prevents their expansion and
      ameliorates cGVHD. Expansion of PSGL-1loCD4+ T cells is also prevented by BCL6 or
      Stat3 deficiency in donor CD4+ T cells, with the induction of cGVHD ameliorated
      by BCL6 deficiency and completely suppressed by Stat3 deficiency in donor CD4+ T
      cells. These results support that Stat3- and BCL6-dependent extrafollicular CD4+
      T and B interactions play critical functions in the pathogenesis of cGVHD.Chronic
      graft-versus-host disease (cGVHD) is mediated by specific CD4 and B cells, but
      the relative contribution of extrafollicular and germinal centre (GC) T-B
      interaction is unclear. Here the authors show that the extrafollicular expansion
      of a specific CD4 T subset is sufficient for inducing cGVHD while GC is
      dispensable.

PMID- 29042533
TI  - A new electrode design for ambipolar injection in organic semiconductors.
AB  - Organic semiconductors have attracted much attention for low-cost, flexible and
      human-friendly optoelectronics. However, achieving high electron-injection
      efficiency is difficult from air-stable electrodes and cannot be equivalent to
      that of holes. Here, we present a novel concept of electrode composed of a
      bilayer of tetratetracontane (TTC) and polycrystalline organic semiconductors (pc
      OSC) covered by a metal layer. Field-effect transistors of single-crystal organic
      semiconductors with the new electrodes of M/pc-OSC/TTC (M: Ca or Au) show both
      highly efficient electron and hole injection. Contact resistance for electron
      injection from Au/pc-OSC/TTC and hole injection from Ca/pc-OSC/TTC are comparable
      to those for electron injection from Ca and hole injection from Au, respectively.
      Furthermore, the highest field-effect mobilities of holes (22 cm2 V-1 s-1) and
      electrons (5.0 cm2 V-1 s-1) are observed in rubrene among field-effect
      transistors with electrodes so far proposed by employing Ca/pc-OSC/TTC and Au/pc
      OSC/TTC electrodes for electron and hole injection, respectively.One of
      technological challenges building organic electronics is efficient injection of
      electrons at metal-semiconductor interfaces compared to that of holes. The
      authors show an air-stable electrode design with induced gap states, which
      support Fermi level pinning and thus ambipolar carrier injection.

PMID- 29042532
TI  - Three-dimensional context rather than NLS amino acid sequence determines importin
      alpha subtype specificity for RCC1.
AB  - Active nuclear import of Ran exchange factor RCC1 is mediated by importin alpha3.
      This pathway is essential to generate a gradient of RanGTP on chromatin that
      directs nucleocytoplasmic transport, mitotic spindle assembly and nuclear
      envelope formation. Here we identify the mechanisms of importin alpha3
      selectivity for RCC1. We find this isoform binds RCC1 with one order of magnitude
      higher affinity than the generic importin alpha1, although the two isoforms share
      an identical NLS-binding groove. Importin alpha3 uses its greater conformational
      flexibility to wedge the RCC1 beta-propeller flanking the NLS against its lateral
      surface, preventing steric clashes with its Armadillo-core. Removing the beta
      propeller, or inserting a linker between NLS and beta-propeller, disrupts
      specificity for importin alpha3, demonstrating the structural context rather than
      NLS sequence determines selectivity for isoform 3. We propose importin alpha3
      evolved to recognize topologically complex NLSs that lie next to bulky domains or
      are masked by quaternary structures.Importin alpha3 facilitates the nuclear
      transport of the Ran guanine nucleotide exchange factor RCC1. Here the authors
      reveal the molecular basis for the selectivity of RCC1 for importin alpha3 vs the
      generic importin alpha1 and discuss the evolution of importin alpha isoforms.

PMID- 29042534
TI  - The microbiota continuum along the female reproductive tract and its relation to
      uterine-related diseases.
AB  - Reports on bacteria detected in maternal fluids during pregnancy are typically
      associated with adverse consequences, and whether the female reproductive tract
      harbours distinct microbial communities beyond the vagina has been a matter of
      debate. Here we systematically sample the microbiota within the female
      reproductive tract in 110 women of reproductive age, and examine the nature of
      colonisation by 16S rRNA gene amplicon sequencing and cultivation. We find
      distinct microbial communities in cervical canal, uterus, fallopian tubes and
      peritoneal fluid, differing from that of the vagina. The results reflect a
      microbiota continuum along the female reproductive tract, indicative of a non
      sterile environment. We also identify microbial taxa and potential functions that
      correlate with the menstrual cycle or are over-represented in subjects with
      adenomyosis or infertility due to endometriosis. The study provides insight into
      the nature of the vagino-uterine microbiome, and suggests that surveying the
      vaginal or cervical microbiota might be useful for detection of common diseases
      in the upper reproductive tract.Whether the female reproductive tract harbours
      distinct microbiomes beyond the vagina has been a matter of debate. Here, the
      authors show a subject-specific continuity in microbial communities at six sites
      along the female reproductive tract, indicative of a non-sterile environment.

PMID- 29042536
TI  - Enhanced generation and anisotropic Coulomb scattering of hot electrons in an
      ultra-broadband plasmonic nanopatch metasurface.
AB  - The creation of energetic electrons through plasmon excitation of nanostructures
      before thermalization has been proposed for a wide number of applications in
      optical energy conversion and ultrafast nanophotonics. However, the use of
      "nonthermal" electrons is primarily limited by both a low generation efficiency
      and their ultrafast decay. We report experimental and theoretical results on the
      use of broadband plasmonic nanopatch metasurfaces comprising a gold substrate
      coupled to silver nanocubes that produce large concentrations of hot electrons,
      which we measure using transient absorption spectroscopy. We find evidence for
      three subpopulations of nonthermal carriers, which we propose arise from
      anisotropic electron-electron scattering within sp-bands near the Fermi surface.
      The bimetallic character of the metasurface strongly impacts the physics, with
      dissipation occurring primarily in the gold, whereas the quantum process of hot
      electron generation takes place in both components. Our calculations show that
      the choice of geometry and materials is crucial for producing strong ultrafast
      nonthermal electron components.The creation of energetic electrons through
      plasmon excitation has implications in optical energy conversion and ultrafast
      nanophotonics. Here, the authors find evidence for three subpopulations of
      nonthermal carriers which arise from anisotropic electron-electron scattering
      near the Fermi surface.

PMID- 29042535
TI  - Mechanism of error-free replication across benzo[a]pyrene stereoisomers by Rev1
      DNA polymerase.
AB  - Benzo[a]pyrene (BP) is a carcinogen in cigarette smoke which, after metabolic
      activation, can react with the exocyclic N 2 amino group of guanine to generate
      four stereoisomeric BP-N 2-dG adducts. Rev1 is unique among translesion synthesis
      DNA polymerases in employing a protein-template-directed mechanism of DNA
      synthesis opposite undamaged and damaged guanine. Here we report high-resolution
      structures of yeast Rev1 with three BP-N 2-dG adducts, namely the 10S (+)-trans
      BP-N 2-dG, 10R (+)-cis-BP-N 2-dG, and 10S ( - )-cis-BP-N 2-dG. Surprisingly, in
      all three structures, the bulky and hydrophobic BP pyrenyl residue is entirely
      solvent-exposed in the major groove of the DNA. This is very different from the
      adduct alignments hitherto observed in free or protein-bound DNA. All complexes
      are well poised for dCTP insertion. Our structures provide a view of cis-BP-N 2
      dG adducts in a DNA polymerase active site, and offer a basis for understanding
      error-free replication of the BP-derived stereoisomeric guanine
      adducts.Benzo[a]pyrene (BP) is a carcinogen in cigarette smoke that upon
      metabolic activation reacts with guanine. Here, the authors present the
      structures of the translesion DNA synthesis polymerase Rev1 in complex with three
      of the four possible stereoisomeric BP-N 2 -dG adducts, which gives insights how
      Rev1 achieves error-free replication.

PMID- 29042537
TI  - Firefly-mimicking intensive and long-lasting chemiluminescence hydrogels.
AB  - Most known chemiluminescence (CL) reactions exhibit flash-type light emission.
      Great efforts have been devoted to the development of CL systems that emit light
      with high intensity and long-lasting time. However, a long-lasting CL system that
      can last for hundreds of hours is yet-to-be-demonstrated. Here we show firefly
      mimicking intensive and long-lasting CL hydrogels consisting of chitosan, CL
      reagent N-(4-aminobutyl)-N-ethylisoluminol (ABEI) and catalyst Co2+. The light
      emission is even visible to naked eyes and lasts for over 150 h when the
      hydrogels are mixed with H2O2. This is attributed to slow-diffusion-controlled
      heterogeneous catalysis. Co2+ located at the skeleton of the hydrogels as an
      active site catalyzes the decomposition of slowly diffusing H2O2, followed by the
      reaction with ABEI to generate intensive and long-lasting CL. This mimics firefly
      bioluminescence system in terms of intensity, duration time and catalytic
      characteristic, which is of potential applications in cold light sources,
      bioassays, biosensors and biological imaging.Great efforts have been devoted to
      the development of chemiluminescence systems that emit light with high intensity
      over long periods of time. Here the authors show, firefly-mimicking intensive and
      long-lasting chemiluminescence hydrogels consisting of chitosan, N-(4-aminobutyl)
      N-ethylisoluminol (ABEI) and catalyst Co2+.

PMID- 29042538
TI  - Volcanic suppression of Nile summer flooding triggers revolt and constrains
      interstate conflict in ancient Egypt.
AB  - Volcanic eruptions provide tests of human and natural system sensitivity to
      abrupt shocks because their repeated occurrence allows the identification of
      systematic relationships in the presence of random variability. Here we show a
      suppression of Nile summer flooding via the radiative and dynamical impacts of
      explosive volcanism on the African monsoon, using climate model output, ice-core
      based volcanic forcing data, Nilometer measurements, and ancient Egyptian
      writings. We then examine the response of Ptolemaic Egypt (305-30 BCE), one of
      the best-documented ancient superpowers, to volcanically induced Nile
      suppression. Eruptions are associated with revolt onset against elite rule, and
      the cessation of Ptolemaic state warfare with their great rival, the Seleukid
      Empire. Eruptions are also followed by socioeconomic stress with increased
      hereditary land sales, and the issuance of priestly decrees to reinforce elite
      authority. Ptolemaic vulnerability to volcanic eruptions offers a caution for all
      monsoon-dependent agricultural regions, presently including 70% of world
      population.The degree to which human societies have responded to past climatic
      changes remains unclear. Here, using a novel combination of approaches, the
      authors show how volcanically-induced suppression of Nile summer flooding led to
      societal unrest in Ptolemaic Egypt (305-30 BCE).

PMID- 29042539
TI  - Inverse poroelasticity as a fundamental mechanism in biomechanics and
      mechanobiology.
AB  - Understanding the mechanisms of deformation of biological materials is important
      for improved diagnosis and therapy, fundamental investigations in mechanobiology,
      and applications in tissue engineering. Here we demonstrate the essential role of
      interstitial fluid mobility in determining the mechanical properties of soft
      tissues. Opposite to the behavior expected for a poroelastic material, the tissue
      volume of different collagenous membranes is observed to strongly decrease with
      tensile loading. Inverse poroelasticity governs monotonic and cyclic responses of
      soft biomembranes, and induces chemo-mechanical coupling, such that tensile
      forces are modulated by the chemical potential of the interstitial fluid.
      Correspondingly, the osmotic pressure varies with mechanical loads, thus
      providing an effective mechanism for mechanotransduction. Water mobility
      determines the tissue's ability to adapt to deformation through compaction and
      dilation of the collagen fiber network. In the near field of defects this
      mechanism activates the reversible formation of reinforcing collagen structures
      which effectively avoid propagation of cracks.How soft tissues respond to
      mechanical load is essential to their biological function. Here, the authors
      discover that - contrary to predictions of poroelasticity - fluid mobility in
      collagenous tissues induces drastic volume decrease with tensile loading and
      pronounced chemo-mechanical coupling.

PMID- 29042540
TI  - Circuit quantum acoustodynamics with surface acoustic waves.
AB  - The experimental investigation of quantum devices incorporating mechanical
      resonators has opened up new frontiers in the study of quantum mechanics at a
      macroscopic level. It has recently been shown that surface acoustic waves (SAWs)
      can be piezoelectrically coupled to superconducting qubits, and confined in high
      quality Fabry-Perot cavities in the quantum regime. Here we present measurements
      of a device in which a superconducting qubit is coupled to a SAW cavity,
      realising a surface acoustic version of cavity quantum electrodynamics. We use
      measurements of the AC Stark shift between the two systems to determine the
      coupling strength, which is in agreement with a theoretical model. This quantum
      acoustodynamics architecture may be used to develop new quantum acoustic devices
      in which quantum information is stored in trapped on-chip acoustic wavepackets,
      and manipulated in ways that are impossible with purely electromagnetic signals,
      due to the 105 times slower mechanical waves.In this work, Manenti et al. present
      measurements of a device in which a tuneable transmon qubit is piezoelectrically
      coupled to a surface acoustic wave cavity, realising circuit quantum
      acoustodynamic architecture. This may be used to develop new quantum acoustic
      devices.

PMID- 29042541
TI  - Resonant out-of-phase fluorescence microscopy and remote imaging overcome
      spectral limitations.
AB  - We present speed out-of-phase imaging after optical modulation (OPIOM), which
      exploits reversible photoswitchable fluorophores as fluorescent labels and
      combines optimized periodic illumination with phase-sensitive detection to
      specifically retrieve the label signal. Speed OPIOM can extract the fluorescence
      emission from a targeted label in the presence of spectrally interfering
      fluorophores and autofluorescence. Up to four fluorescent proteins exhibiting a
      similar green fluorescence have been distinguished in cells either sequentially
      or in parallel. Speed OPIOM is compatible with imaging biological processes in
      real time in live cells. Finally speed OPIOM is not limited to microscopy but is
      relevant for remote imaging as well, in particular, under ambient light. Thus,
      speed OPIOM has proved to enable fast and quantitative live microscopic and
      remote-multiplexed fluorescence imaging of biological samples while filtering out
      noise, interfering fluorophores, as well as ambient light.Generally, fluorescence
      imaging needs to be done in a dark environment using molecules with spectrally
      separated emissions. Here, Querard et al. develop a protocol for high-speed
      imaging and remote sensing of spectrally overlapping reversible photoswitchable
      fluorophores in ambient light.

PMID- 29042543
TI  - Quantum sensing of weak radio-frequency signals by pulsed Mollow absorption
      spectroscopy.
AB  - Quantum sensors-qubits sensitive to external fields-have become powerful
      detectors for various small acoustic and electromagnetic fields. A major key to
      their success have been dynamical decoupling protocols which enhance sensitivity
      to weak oscillating (AC) signals. Currently, those methods are limited to signal
      frequencies below a few MHz. Here we harness a quantum-optical effect, the Mollow
      triplet splitting of a strongly driven two-level system, to overcome this
      limitation. We microscopically understand this effect as a pulsed dynamical
      decoupling protocol and find that it enables sensitive detection of fields close
      to the driven transition. Employing a nitrogen-vacancy center, we detect GHz
      microwave fields with a signal strength (Rabi frequency) below the current
      detection limit, which is set by the center's spectral linewidth [Formula: see
      text]. Pushing detection sensitivity to the much lower 1/T 2 limit, this scheme
      could enable various applications, most prominently coherent coupling to single
      phonons and microwave photons.Dynamical decoupling protocols can enhance the
      sensitivity of quantum sensors but this is limited to signal frequencies below a
      few MHz. Here, Joas et al. use the Mollow triplet splitting in a nitrogen-vacancy
      centre to overcome this limitation, enabling sensitive detection of signals in
      the GHz range.

PMID- 29042542
TI  - Tyrosine phosphorylation of the GARU E3 ubiquitin ligase promotes gibberellin
      signalling by preventing GID1 degradation.
AB  - Gibberellin (GA) is a major hormone for plant growth and development. GA response
      is derived from the degradation of DELLA repressor proteins after GA-dependent
      complex formation of the GID1 GA receptor with DELLA. Genistein is a known
      tyrosine (Tyr) kinase inhibitor and inhibits DELLA degradation. However, the
      biological role of Tyr phosphorylation on the GA response remains unclear. Here,
      we demonstrate that GARU (GA receptor RING E3 ubiquitin ligase) mediates
      ubiquitin-dependent degradation of GID1, and that the TAGK2 plant Tyr-kinase is a
      target of genistein and inhibits GARU-GID1A interactions by phosphorylation of
      GARU at Tyr321. Genistein induces degradation of GID1 and accumulation of DELLA.
      Conversely, Arabidopsis garu mutant and TAGK2-overexpressing plants accelerate
      GID1 stabilization and DELLA degradation. Under salt stress, GARU suppresses seed
      germination. We propose that GA response is negatively regulated by GARU
      dependent GID1 ubiquitination and positively by Tyr phosphorylation of GARU by
      TAGK2, and genistein inhibits GA signaling by TAGK2 inhibition.Plants respond to
      gibberellins via GID1-dependent degradation of DELLA proteins. Here, Nemoto et
      al. show that the gibberellin response is positively regulated by tyrosine
      phosphorylation of GARU, an E3 ubiquitin ligase that mediates degradation of
      GID1.

PMID- 29042544
TI  - Origami-based tunable truss structures for non-volatile mechanical memory
      operation.
AB  - Origami has recently received significant interest from the scientific community
      as a method for designing building blocks to construct metamaterials. However,
      the primary focus has been placed on their kinematic applications by leveraging
      the compactness and auxeticity of planar origami platforms. Here, we present
      volumetric origami cells-specifically triangulated cylindrical origami (TCO)-with
      tunable stability and stiffness, and demonstrate their feasibility as non
      volatile mechanical memory storage devices. We show that a pair of TCO cells can
      develop a double-well potential to store bit information. What makes this origami
      based approach more appealing is the realization of two-bit mechanical memory, in
      which two pairs of TCO cells are interconnected and one pair acts as a control
      for the other pair. By assembling TCO-based truss structures, we experimentally
      verify the tunable nature of the TCO units and demonstrate the operation of
      purely mechanical one- and two-bit memory storage prototypes.Origami is a popular
      method to design building blocks for mechanical metamaterials. Here, the authors
      assemble a volumetric origami-based structure, predict its axial and rotational
      movements during folding, and demonstrate the operation of mechanical one- and
      two-bit memory storage.

PMID- 29042545
TI  - Gate-controlled reversible rectifying behaviour in tunnel contacted atomically
      thin MoS2 transistor.
AB  - Atomically thin two-dimensional semiconducting materials integrated into van der
      Waals heterostructures have enabled architectures that hold great promise for
      next generation nanoelectronics. However, challenges still remain to enable their
      applications as compliant materials for integration in logic devices. Here, we
      devise a reverted stacking technique to intercalate a wrinkle-free boron nitride
      tunnel layer between MoS2 channel and source drain electrodes. Vertical
      tunnelling of electrons therefore makes it possible to suppress the Schottky
      barriers and Fermi level pinning, leading to homogeneous gate-control of the
      channel chemical potential across the bandgap edges. The observed features of
      ambipolar pn to np diode, which can be reversibly gate tuned, paves the way for
      future logic applications and high performance switches based on atomically thin
      semiconducting channel.Van der Waals heterostructures of atomically thin
      materials hold promise for nanoelectronics. Here, the authors demonstrate a
      reverted stacking fabrication method for heterostructures and devise a vertical
      tunnel-contacted MoS2 transistor, enabling gate tunable rectification and
      reversible pn to np diode behaviour.

PMID- 29042546
TI  - Anomeric memory of the glycosidic bond upon fragmentation and its consequences
      for carbohydrate sequencing.
AB  - Deciphering the carbohydrate alphabet is problematic due to its unique complexity
      among biomolecules. Strikingly, routine sequencing technologies-which are
      available for proteins and DNA and have revolutionised biology-do not exist for
      carbohydrates. This lack of structural tools is identified as a crucial
      bottleneck, limiting the full development of glycosciences and their considerable
      potential impact for the society. In this context, establishing generic
      carbohydrate sequencing methods is both a major scientific challenge and a
      strategic priority. Here we show that a hybrid analytical approach integrating
      molecular spectroscopy with mass spectrometry provides an adequate metric to
      resolve carbohydrate isomerisms, i.e the monosaccharide content, anomeric
      configuration, regiochemistry and stereochemistry of the glycosidic linkage. On
      the basis of the spectroscopic discrimination of MS fragments, we report the
      unexpected demonstration of the anomeric memory of the glycosidic bond upon
      fragmentation. This remarkable property is applied to de novo sequencing of
      underivatized oligosaccharides.Establishing generic carbohydrate sequencing
      methods is both a major scientific challenge and a strategic priority. Here the
      authors show a hybrid analytical approach integrating molecular spectroscopy and
      mass spectrometry to resolve carbohydrate isomerism, anomeric configuration,
      regiochemistry and stereochemistry.

PMID- 29042547
TI  - Full-gap superconductivity in spin-polarised surface states of topological
      semimetal beta-PdBi2.
AB  - A bulk superconductor possessing a topological surface state at the Fermi level
      is a promising system to realise long-sought topological superconductivity.
      Although several candidate materials have been proposed, experimental
      demonstrations concurrently exploring spin textures and superconductivity at the
      surface have remained elusive. Here we perform spectroscopic-imaging scanning
      tunnelling microscopy on the centrosymmetric superconductor beta-PdBi2 that hosts
      a topological surface state. By combining first-principles electronic-structure
      calculations and quasiparticle interference experiments, we determine the spin
      textures at the surface, and show not only the topological surface state but also
      all other surface bands exhibit spin polarisations parallel to the surface. We
      find that the superconducting gap fully opens in all the spin-polarised surface
      states. This behaviour is consistent with a possible spin-triplet order parameter
      expected for such in-plane spin textures, but the observed superconducting gap
      amplitude is comparable to that of the bulk, suggesting that the spin-singlet
      component is predominant in beta-PdBi2.Although several materials have been
      proposed as topological superconductors, spin textures and superconductivity at
      the surface remain elusive. Here, Iwaya et al. determine the spin textures at the
      surface of a superconductor beta-PdBi2 and find the superconducting gap opening
      in all spin-polarised surface states.

PMID- 29042549
TI  - Mechanoresponsive lipid-protein nanoglobules facilitate reversible fibre
      formation in velvet worm slime.
AB  - Velvet worms eject a fluid capture slime that can be mechanically drawn into
      stiff biopolymeric fibres. Remarkably, these fibres can be dissolved by extended
      exposure to water, and new regenerated fibres can be drawn from the dissolved
      fibre solution-indicating a fully recyclable process. Here, we perform a
      multiscale structural and compositional investigation of this reversible
      fabrication process with the velvet worm Euperipatoides rowelli, revealing that
      biopolymeric fibre assembly is facilitated via mono-disperse lipid-protein
      nanoglobules. Shear forces cause nanoglobules to self-assemble into nano- and
      microfibrils, which can be drawn into macroscopic fibres with a protein-enriched
      core and lipid-rich coating. Fibre dissolution in water leads to re-formation of
      nanoglobules, suggesting that this dynamic supramolecular assembly of
      mechanoresponsive protein-building blocks is mediated by reversible non-covalent
      interactions. These findings offer important mechanistic insights into the role
      of mechanochemical processes in bio-fibre formation, providing potential avenues
      for sustainable material fabrication processes.Velvet worms expel a fluid slime
      that, under shear force, forms stiff fibres that can be dissolved and then
      regenerated. Here, the authors reveal that the recyclability of these biopolymers
      relies on mechanoresponsive lipid-protein nanoglobules in the slime that
      reversibly self-assemble into fibrils.

PMID- 29042550
TI  - Correspondence: Response of a gravimeter to an instantaneous step in gravity.

PMID- 29042548
TI  - Human mesenchymal stromal cells transplanted into mice stimulate renal tubular
      cells and enhance mitochondrial function.
AB  - Mesenchymal stromal cells (MSCs) are renoprotective and drive regeneration
      following injury, although cellular targets of such an effect are still ill
      defined. Here, we show that human umbilical cord (UC)-MSCs transplanted into mice
      stimulate tubular cells to regain mitochondrial mass and function, associated
      with enhanced microtubule-rich projections that appear to mediate mitochondrial
      trafficking to create a reparative dialogue among adjacent tubular cells.
      Treatment with UC-MSCs in mice with cisplatin-induced acute kidney injury (AKI)
      regulates mitochondrial biogenesis in proximal tubuli by enhancing PGC1alpha
      expression, NAD+ biosynthesis and Sirtuin 3 (SIRT3) activity, thus fostering
      antioxidant defenses and ATP production. The functional role of SIRT3 in tubular
      recovery is highlighted by data that in SIRT3-deficient mice with AKI, UC-MSC
      treatment fails to induce renoprotection. These data document a previously
      unrecognized mechanism through which UC-MSCs facilitate renal repair, so as to
      induce global metabolic reprogramming of damaged tubular cells to sustain energy
      supply.Mesenchymal stromal cells drive renal regeneration following injury. Here,
      the authors show that human mesenchymal stromal cells, when transplanted into
      mice with acute kidney injury, stimulate renal tubular cell growth and enhance
      mitochondrial function via SIRT3.

PMID- 29042552
TI  - Mass spectrometry sequencing of long digital polymers facilitated by programmed
      inter-byte fragmentation.
AB  - In the context of data storage miniaturization, it was recently shown that
      digital information can be stored in the monomer sequences of non-natural
      macromolecules. However, the sequencing of such digital polymers is currently
      limited to short chains. Here, we report that intact multi-byte digital polymers
      can be sequenced in a moderate resolution mass spectrometer and that full
      sequence coverage can be attained without requiring pre-analysis digestion or the
      help of sequence databases. In order to do so, the polymers are designed to
      undergo controlled fragmentations in collision-induced dissociation conditions.
      Each byte of the sequence is labeled by an identification tag and a weak
      alkoxyamine group is placed between 2 bytes. As a consequence of this design, the
      NO-C bonds break first upon collisional activation, thus leading to a pattern of
      mass tag-shifted intact bytes. Afterwards, each byte is individually sequenced in
      pseudo-MS3 conditions and the whole sequence is found.Digital information can be
      stored in monomer sequences of non-natural macromolecules, but only short chains
      can be read. Here the authors show long multi-byte digital polymers sequenced in
      a moderate resolution mass spectrometer. Full sequence coverage can be attained
      without pre-analysis digestion or the help from sequence databases.

PMID- 29042551
TI  - Integrating evolutionary and regulatory information with a multispecies approach
      implicates genes and pathways in obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder is a severe psychiatric disorder linked to
      abnormalities in glutamate signaling and the cortico-striatal circuit. We
      sequenced coding and regulatory elements for 608 genes potentially involved in
      obsessive-compulsive disorder in human, dog, and mouse. Using a new method that
      prioritizes likely functional variants, we compared 592 cases to 560 controls and
      found four strongly associated genes, validated in a larger cohort. NRXN1 and
      HTR2A are enriched for coding variants altering postsynaptic protein-binding
      domains. CTTNBP2 (synapse maintenance) and REEP3 (vesicle trafficking) are
      enriched for regulatory variants, of which at least six (35%) alter transcription
      factor-DNA binding in neuroblastoma cells. NRXN1 achieves genome-wide
      significance (p = 6.37 * 10-11) when we include 33,370 population-matched
      controls. Our findings suggest synaptic adhesion as a key component in compulsive
      behaviors, and show that targeted sequencing plus functional annotation can
      identify potentially causative variants, even when genomic data are
      limited.Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with
      symptoms including intrusive thoughts and time-consuming repetitive behaviors.
      Here Noh and colleagues identify genes enriched for functional variants
      associated with increased risk of OCD.

PMID- 29042553
TI  - Molecular analysis of high-grade serous ovarian carcinoma with and without
      associated serous tubal intra-epithelial carcinoma.
AB  - Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate
      in the distal portion of the fallopian tube. Serous tubal intra-epithelial
      carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~
      50% of advanced stage cases. To better understand the molecular etiology of
      HGSCs, we report a multi-center integrated genomic analysis of advanced stage
      tumors with and without STIC lesions and normal tissues. The most significant
      focal DNA SCNAs were shared between cases with and without STIC lesions. The RNA
      sequence and the miRNA data did not identify any clear separation between cases
      with and without STIC lesions. HGSCs had molecular profiles more similar to
      normal fallopian tube epithelium than ovarian surface epithelium or peritoneum.
      The data suggest that the molecular features of HGSCs with and without associated
      STIC lesions are mostly shared, indicating a common biologic origin, likely to be
      the distal fallopian tube among all cases.High-grade serous carcinomas (HGSCs)
      are associated with precursor lesions (STICs) in the fallopian epithelium in only
      half of the cases. Here the authors report the molecular analysis of HGSCs with
      and without associated STICs and show similar profiles supporting a common origin
      for all HGSCs.

PMID- 29042554
TI  - Glycaemic control boosts glucosylated nanocarrier crossing the BBB into the
      brain.
AB  - Recently, nanocarriers that transport bioactive substances to a target site in
      the body have attracted considerable attention and undergone rapid progression in
      terms of the state of the art. However, few nanocarriers can enter the brain via
      a systemic route through the blood-brain barrier (BBB) to efficiently reach
      neurons. Here we prepare a self-assembled supramolecular nanocarrier with a
      surface featuring properly configured glucose. The BBB crossing and brain
      accumulation of this nanocarrier are boosted by the rapid glycaemic increase
      after fasting and by the putative phenomenon of the highly expressed glucose
      transporter-1 (GLUT1) in brain capillary endothelial cells migrating from the
      luminal to the abluminal plasma membrane. The precisely controlled glucose
      density on the surface of the nanocarrier enables the regulation of its
      distribution within the brain, and thus is successfully optimized to increase the
      number of nanocarriers accumulating in neurons.There are only a few examples of
      nanocarriers that can transport bioactive substances across the blood-brain
      barrier. Here the authors show that by rapid glycaemic increase the accumulation
      of a glucosylated nanocarrier in the brain can be controlled.

PMID- 29042555
TI  - Super-formable pure magnesium at room temperature.
AB  - Magnesium, the lightest structural metal, is difficult to form at room
      temperature due to an insufficient number of deformation modes imposed by its
      hexagonal structure and a strong texture developed during thermomechanical
      processes. Although appropriate alloying additions can weaken the texture,
      formability improvement is limited because alloying additions do not
      fundamentally alter deformation modes. Here we show that magnesium can become
      super-formable at room temperature without alloying. Despite possessing a strong
      texture, magnesium can be cold rolled to a strain at least eight times that
      possible in conventional processing. The resultant cold-rolled sheet can be
      further formed without cracking due to grain size reduction to the order of one
      micron and inter-granular mechanisms becoming dominant, rather than the usual
      slip and twinning. These findings provide a pathway for developing highly
      formable products from magnesium and other hexagonal metals that are
      traditionally difficult to form at room temperature.Replacing steel or aluminium
      vehicle parts with magnesium would result in reduced emissions, but shaping
      magnesium without cracking remains challenging. Here, the authors successfully
      extrude and roll textured magnesium into ductile foil at low temperatures by
      activating intra-granular mechanisms.

PMID- 29042556
TI  - Nanoscale control of competing interactions and geometrical frustration in a
      dipolar trident lattice.
AB  - Geometrical frustration occurs when entities in a system, subject to given
      lattice constraints, are hindered to simultaneously minimize their local
      interactions. In magnetism, systems incorporating geometrical frustration are
      fascinating, as their behavior is not only hard to predict, but also leads to the
      emergence of exotic states of matter. Here, we provide a first look into an
      artificial frustrated system, the dipolar trident lattice, where the balance of
      competing interactions between nearest-neighbor magnetic moments can be directly
      controlled, thus allowing versatile tuning of geometrical frustration and
      manipulation of ground state configurations. Our findings not only provide the
      basis for future studies on the low-temperature physics of the dipolar trident
      lattice, but also demonstrate how this frustration-by-design concept can deliver
      magnetically frustrated metamaterials.Artificial magnetic nanostructures enable
      the study of competing frustrated interactions with more control over the system
      parameters than is possible in magnetic materials. Farhan et al. present a two
      dimensional lattice geometry where the frustration can be controlled by tuning
      the unit cell parameters.

PMID- 29042557
TI  - Mechanocaloric effects in superionic thin films from atomistic simulations.
AB  - Solid-state cooling is an energy-efficient and scalable refrigeration technology
      that exploits the adiabatic variation of a crystalline order parameter under an
      external field (electric, magnetic, or mechanic). The mechanocaloric effect bears
      one of the greatest cooling potentials in terms of energy efficiency owing to its
      large available latent heat. Here we show that giant mechanocaloric effects occur
      in thin films of well-known families of fast-ion conductors, namely Li-rich
      (Li3OCl) and type-I (AgI), an abundant class of materials that routinely are
      employed in electrochemistry cells. Our simulations reveal that at room
      temperature AgI undergoes an adiabatic temperature shift of 38 K under a biaxial
      stress of 1 GPa. Likewise, Li3OCl displays a cooling capacity of 9 K under
      similar mechanical conditions although at a considerably higher temperature. We
      also show that ionic vacancies have a detrimental effect on the cooling
      performance of superionic thin films. Our findings should motivate experimental
      mechanocaloric searches in a wide variety of already known superionic
      materials.Mechanocaloric effects are a promising path towards solid-state
      cooling. Here the authors perform atomistic simulations on the well-known fast
      ion conductor silver iodide and computationally predict a sizeable mechanocaloric
      effect under biaxial strain.

PMID- 29042558
TI  - Remote light-controlled intracellular target recognition by photochromic
      fluorescent glycoprobes.
AB  - Development of powerful fluorescence imaging probes and techniques sets the basis
      for the spatiotemporal tracking of cells at different physiological and
      pathological stages. While current imaging approaches rely on passive probe
      analyte interactions, here we develop photochromic fluorescent glycoprobes
      capable of remote light-controlled intracellular target recognition. Conjugation
      between a fluorophore and spiropyran produces the photochromic probe, which is
      subsequently equipped with a glycoligand "antenna" to actively localize a target
      cell expressing a selective receptor. We demonstrate that the amphiphilic
      glycoprobes that form micelles in water can selectively enter the target cell to
      operate photochromic cycling as controlled by alternate UV/Vis irradiations. We
      further show that remote light conversion of the photochromic probe from one
      isomeric state to the other activates its reactivity toward a target
      intracellular analyte, producing locked fluorescence that is no longer
      photoisomerizable. We envision that this research may spur the use of
      photochromism for the development of bioimaging probes.Fluorescence sensing in
      biological environments is prone to background signal interference. Here the
      authors design a photochromic fluorescent glycoprobe for light-controlled photo
      switchable cell imaging and photo-activated target recognition, resulting in an
      increased sensing precision.

PMID- 29042559
TI  - Growth mechanism of strongly emitting CH3NH3PbBr3 perovskite nanocrystals with a
      tunable bandgap.
AB  - Metal halide perovskite nanocrystals are promising materials for a diverse range
      of applications, such as light-emitting devices and photodetectors. We
      demonstrate the bandgap tunability of strongly emitting CH3NH3PbBr3 nanocrystals
      synthesized at both room and elevated (60  degrees C) temperature through the
      variation of the precursor and ligand concentrations. We discuss in detail the
      role of two ligands, oleylamine and oleic acid, in terms of the coordination of
      the lead precursors and the nanocrystal surface. The growth mechanism of
      nanocrystals is elucidated by combining the experimental results with the
      principles of nucleation/growth models. The proposed formation mechanism of
      perovskite nanocrystals will be helpful for further studies in this field and can
      be used as a guide to improve the synthetic methods in the future.The development
      of perovskite nanocrystals is limited by poor mechanistic understanding of their
      growth. Here, the authors systematically study the ligand-assisted
      reprecipitation synthesis of CH3NH3PbBr3 nanocrystals, revealing the effect of
      precursor and ligand concentrations on bandgap tunability.

PMID- 29042560
TI  - Mitigating oxygen loss to improve the cycling performance of high capacity cation
      disordered cathode materials.
AB  - Recent progress in the understanding of percolation theory points to cation
      disordered lithium-excess transition metal oxides as high-capacity lithium-ion
      cathode materials. Nevertheless, the oxygen redox processes required for these
      materials to deliver high capacity can trigger oxygen loss, which leads to the
      formation of resistive surface layers on the cathode particles. We demonstrate
      here that, somewhat surprisingly, fluorine can be incorporated into the bulk of
      disordered lithium nickel titanium molybdenum oxides using a standard solid-state
      method to increase the nickel content, and that this compositional modification
      is very effective in reducing oxygen loss, improving energy density, average
      voltage, and rate performance. We argue that the valence reduction on the anion
      site, offered by fluorine incorporation, opens up significant opportunities for
      the design of high-capacity cation-disordered cathode materials.The performance
      of lithium-excess cation-disordered oxides as cathode materials relies on the
      extent to which the oxygen loss during cycling is mitigated. Here, the authors
      show that incorporating fluorine is an effective strategy which substantially
      improves the cycling stability of such a material.

PMID- 29042561
TI  - AUNIP/C1orf135 directs DNA double-strand breaks towards the homologous
      recombination repair pathway.
AB  - DNA double-strand breaks (DSBs) are mainly repaired by either homologous
      recombination (HR) or non-homologous end-joining (NHEJ). Here, we identify
      AUNIP/C1orf135, a largely uncharacterized protein, as a key determinant of DSB
      repair pathway choice. AUNIP physically interacts with CtIP and is required for
      efficient CtIP accumulation at DSBs. AUNIP possesses intrinsic DNA-binding
      ability with a strong preference for DNA substrates that mimic structures
      generated at stalled replication forks. This ability to bind DNA is necessary for
      the recruitment of AUNIP and its binding partner CtIP to DSBs, which in turn
      drives CtIP-dependent DNA-end resection and HR repair. Accordingly, loss of AUNIP
      or ablation of its ability to bind to DNA results in cell hypersensitivity toward
      a variety of DSB-inducing agents, particularly those that induce replication
      associated DSBs. Our findings provide new insights into the molecular mechanism
      by which DSBs are recognized and channeled to the HR repair pathway.DNA double
      strand breaks can be repaired by homology-independent or homology-directed
      mechanisms. The choice between these pathways is a key event for genomic
      stability maintenance. Here the authors identify and characterize AUNIP, as a
      factor involved in tilting the balance towards homology repair.

PMID- 29042563
TI  - Erratum: A novel humanized mouse lacking murine p450 oxidoreductase for studying
      human drug metabolism.
AB  - An incorrect version of the Supplementary Information was inadvertently published
      with this Article where the wrong file was included. The HTML has been updated to
      include the correct version of the Supplementary Information.

PMID- 29042562
TI  - Cis P-tau is induced in clinical and preclinical brain injury and contributes to
      post-injury sequelae.
AB  - Traumatic brain injury (TBI) is characterized by acute neurological dysfunction
      and associated with the development of chronic traumatic encephalopathy (CTE) and
      Alzheimer's disease. We previously showed that cis phosphorylated tau (cis P
      tau), but not the trans form, contributes to tau pathology and functional
      impairment in an animal model of severe TBI. Here we found that in human samples
      obtained post TBI due to a variety of causes, cis P-tau is induced in cortical
      axons and cerebrospinal fluid and positively correlates with axonal injury and
      clinical outcome. Using mouse models of severe or repetitive TBI, we showed that
      cis P-tau elimination with a specific neutralizing antibody administered
      immediately or at delayed time points after injury, attenuates the development of
      neuropathology and brain dysfunction during acute and chronic phases including
      CTE-like pathology and dysfunction after repetitive TBI. Thus, cis P-tau
      contributes to short-term and long-term sequelae after TBI, but is effectively
      neutralized by cis antibody treatment.Induction of the cis form of phosphorylated
      tau (cis P-tau) has previously been shown to occur in animal models of traumatic
      brain injury (TBI), and blocking this form of tau using antibody was beneficial
      in a rodent model of severe TBI. Here the authors show that cis P-tau induction
      is a feature of several different forms of TBI in humans, and that administration
      of cis P-tau targeting antibody to rodents reduces or delays pathological
      features of TBI.

PMID- 29042564
TI  - Real-time tracking of metal nucleation via local perturbation of hydration
      layers.
AB  - The real-time visualization of stochastic nucleation events at electrode surfaces
      is one of the most complex challenges in electrochemical phase formation. The
      early stages of metal deposition on foreign substrates are characterized by a
      highly dynamic process in which nanoparticles nucleate and dissolve prior to
      reaching a critical size for deposition and growth. Here, high-speed non-contact
      lateral molecular force microscopy employing vertically oriented probes is
      utilized to explore the evolution of hydration layers at electrode surfaces with
      the unprecedented spatiotemporal resolution, and extremely low probe-surface
      interaction forces required to avoid disruption or shielding the critical nucleus
      formation. To the best of our knowledge, stochastic nucleation events of
      nanoscale copper deposits are visualized in real time for the first time and a
      highly dynamic topographic environment prior to the formation of critical nuclei
      is unveiled, featuring formation/re-dissolution of nuclei, two-dimensional
      aggregation and nuclei growth.Electrochemical deposition is important for
      industrial processes however, tracking the early stages of metallic phase
      nucleation is challenging. Here, the authors visualize the birth and growth of
      metal nuclei at electrode surfaces in real time via high-speed non-contact
      lateral molecular force microscopy.

PMID- 29042565
TI  - Topological quantum phase transition from mirror to time reversal symmetry
      protected topological insulator.
AB  - Topological insulators constitute a new phase of matter protected by symmetries.
      Time-reversal symmetry protects strong topological insulators of the Z2 class,
      which possess an odd number of metallic surface states with dispersion of a Dirac
      cone. Topological crystalline insulators are merely protected by individual
      crystal symmetries and exist for an even number of Dirac cones. Here, we
      demonstrate that Bi-doping of Pb1-x Sn x Se (111) epilayers induces a quantum
      phase transition from a topological crystalline insulator to a Z2 topological
      insulator. This occurs because Bi-doping lifts the fourfold valley degeneracy and
      induces a gap at [Formula: see text], while the three Dirac cones at the
      [Formula: see text] points of the surface Brillouin zone remain intact. We
      interpret this new phase transition as caused by a lattice distortion. Our
      findings extend the topological phase diagram enormously and make strong
      topological insulators switchable by distortions or electric fields.Transitions
      between topological phases of matter protected by different symmetries remain
      rare. Here, Mandal et al. report a quantum phase transition from a topological
      crystalline insulator to a Z2 topological insulator by doping Bi into Pb1-x Sn x
      Se (111) thin films.

PMID- 29042566
TI  - Anomalous quantization trajectory and parity anomaly in Co cluster decorated
      BiSbTeSe2 nanodevices.
AB  - Dirac Fermions with different helicities exist on the top and bottom surfaces of
      topological insulators, offering a rare opportunity to break the degeneracy
      protected by the no-go theorem. Through the application of Co clusters, quantum
      Hall plateaus were modulated for the topological insulator BiSbTeSe2, allowing an
      optimized surface transport. Here, using renormalization group flow diagrams, we
      show the extraction of two sets of converging points in the conductivity tensor
      space, revealing that the top surface exhibits an anomalous quantization
      trajectory, while the bottom surface retains the 1/2 quantization. Co clusters
      are believed to induce a sizeable Zeeman gap ( > 4.8 meV) through
      antiferromagnetic exchange coupling, which delays the Landau level hybridization
      on the top surface for a moderate magnetic field. A quasi-half-integer plateau
      also appears at -7.2 Tesla. This allows us to study the interesting physics of
      parity anomaly, and paves the way for further studies simulating exotic particles
      in condensed matter physics.The topological surface states usually appear in
      pairs in a topological insulator, with one on the top surface and the other on
      the bottom surface. Here, Zhang et al. utilize Co cluster to induce a Zeeman gap
      on one surface through antiferromagnetic exchange coupling, and observe a quasi
      half-integer plateau, suggesting the parity anomaly of Dirac fermions.

PMID- 29042568
TI  - Combined Microscopy, Calorimetry and X-ray Scattering Study of Fluorinated
      Dimesogens.
AB  - The material FDO11DFCB3 (compound 2 in this work) remains the only example of a
      liquid-crystalline material to exhibit a phase transition from the heliconical
      twist-bend phase into a lamellar smectic A mesophase, additionally this material
      exhibits a previously unidentified mesophase. We have prepared and characterised
      several homologues of this compound, with each material subjected to an in-depth
      analysis by optical microscopy, calorimetry and small angle X-ray scattering
      studies. Despite FDO11DFCB3 being similar in chemical structure to the novel
      materials presented herein its liquid-crystalline behaviour is rather different,
      indicating an unexpected sensitivity of the twist-bend phase to molecular
      structure.

PMID- 29042567
TI  - Mapping the ultrafast flow of harvested solar energy in living photosynthetic
      cells.
AB  - Photosynthesis transfers energy efficiently through a series of antenna complexes
      to the reaction center where charge separation occurs. Energy transfer in vivo is
      primarily monitored by measuring fluorescence signals from the small fraction of
      excitations that fail to result in charge separation. Here, we use two
      dimensional electronic spectroscopy to follow the entire energy transfer process
      in a thriving culture of the purple bacteria, Rhodobacter sphaeroides. By
      removing contributions from scattered light, we extract the dynamics of energy
      transfer through the dense network of antenna complexes and into the reaction
      center. Simulations demonstrate that these dynamics constrain the membrane
      organization into small pools of core antenna complexes that rapidly trap energy
      absorbed by surrounding peripheral antenna complexes. The rapid trapping and
      limited back transfer of these excitations lead to transfer efficiencies of 83%
      and a small functional light-harvesting unit.During photosynthesis, energy is
      transferred from photosynthetic antenna to reaction centers via ultrafast energy
      transfer. Here the authors track energy transfer in photosynthetic bacteria using
      two-dimensional electronic spectroscopy and show that these transfer dynamics
      constrain antenna complex organization.

PMID- 29042569
TI  - Switching behavior of droplets crossing nodes on a fiber network.
AB  - Lately, curious structures have been erected in arid regions: they are large nets
      able to catch water from fog. Tiny droplets condense on the mesh and are
      collected on the bottom of it. This innovative technology is crucial to obtain
      drinkable water in these inhospitable areas. Many studies aim to understand the
      behavior of droplets trapped on this entanglement of fibers. However, the motion
      of a droplet sliding on a network of inclined fibers and encountering several
      crossings when going down remains an open question. Here, we look at the path
      chosen by such a drop and, especially, we analyze its behavior at the different
      nodes of the array. We show that droplets may change from one fiber to another
      one depending on the slope and the diameter of these fibers. We prove that we can
      force a droplet to follow a specific path simply by carefully designing the fiber
      mesh. These findings are expected to provide a very convenient way to manipulate
      small droplets in applications from microfluidics to fog harvesting.

PMID- 29042570
TI  - Fan-out Estimation in Spin-based Quantum Computer Scale-up.
AB  - Solid-state spin-based qubits offer good prospects for scaling based on their
      long coherence times and nexus to large-scale electronic scale-up technologies.
      However, high-threshold quantum error correction requires a two-dimensional qubit
      array operating in parallel, posing significant challenges in fabrication and
      control. While architectures incorporating distributed quantum control meet this
      challenge head-on, most designs rely on individual control and readout of all
      qubits with high gate densities. We analysed the fan-out routing overhead of a
      dedicated control line architecture, basing the analysis on a generalised solid
      state spin qubit platform parameterised to encompass Coulomb confined (e.g. donor
      based spin qubits) or electrostatically confined (e.g. quantum dot based spin
      qubits) implementations. The spatial scalability under this model is estimated
      using standard electronic routing methods and present-day fabrication
      constraints. Based on reasonable assumptions for qubit control and readout we
      estimate 102-105 physical qubits, depending on the quantum interconnect
      implementation, can be integrated and fanned-out independently. Assuming
      relatively long control-free interconnects the scalability can be extended.
      Ultimately, the universal quantum computation may necessitate a much higher
      number of integrated qubits, indicating that higher dimensional electronics
      fabrication and/or multiplexed distributed control and readout schemes may be the
      preferredstrategy for large-scale implementation.

PMID- 29042571
TI  - A Novel Technique for Accelerated Culture of Murine Mesenchymal Stem Cells that
      Allows for Sustained Multipotency.
AB  - Bone marrow derived mesenchymal stem cells (MSCs) are regularly utilized for
      translational therapeutic strategies including cell therapy, tissue engineering,
      and regenerative medicine and are frequently used in preclinical mouse models for
      both mechanistic studies and screening of new cell based therapies. Current
      methods to culture murine MSCs (mMSCs) select for rapidly dividing colonies and
      require long-term expansion. These methods thus require months of culture to
      generate sufficient cell numbers for feasibility studies in a lab setting and the
      cell populations often have reduced proliferation and differentiation potential,
      or have become immortalized cells. Here we describe a simple and reproducible
      method to generate mMSCs by utilizing hypoxia and basic fibroblast growth factor
      supplementation. Cells produced using these conditions were generated 2.8 times
      faster than under traditional methods and the mMSCs showed decreased senescence
      and maintained their multipotency and differentiation potential until passage 11
      and beyond. Our method for mMSC isolation and expansion will significantly
      improve the utility of this critical cell source in pre-clinical studies for the
      investigation of MSC mechanisms, therapies, and cell manufacturing strategies.

PMID- 29042573
TI  - Efficient induction of comprehensive immune responses to control pathogenic E.
      coli by clay nano-adjuvant with the moderate size and surface charge.
AB  - In recent decades, diseases caused by pathogenic Escherichia coli (E. coli),
      enterohaemorrhagic E. coli (EHEC) O26 have been increasingly reported worldwide,
      which are as severe as those caused by EHEC strain O157:H7 and require effective
      intervention strategies. Herein, we report the application of clay nanoparticles,
      i.e. hectorites as effective nano-adjuvants for vaccination against EHEC O26
      colonization. We show that medium size HEC (hectorite, around 73~77 nm diameter)
      is able to induce efficient humoral and cellular immune responses against EHEC
      antigen - intimin beta (IB), which are significantly higher than those triggered
      by commercially used adjuvants - QuilA and Alum. We also demonstrate that mice
      immunized with IB adjuvanted with HEC nanoparticles elicit sufficient secretion
      of mucosal IgA, capable of providing effective protection against EHEC O26
      binding to ruminant and human cells. In addition, we demonstrate for the first
      time that hectorites are able to initiate maturation of RAW 264.7 macrophages,
      inducing expression of co-stimulatory cytokines at a low nanoparticle
      concentration (10 MUg/mL). Together these data strongly suggest that hectorite
      with optimized size is a highly efficient vaccine nano-adjuvant.

PMID- 29042572
TI  - Diagonal Earlobe Crease is a Visible Sign for Cerebral Small Vessel Disease and
      Amyloid-beta.
AB  - We investigated the frequency and clinical significance of diagonal earlobe
      crease (DELC) in cognitively impaired patients using imaging biomarkers, such as
      white matter hyperintensities (WMH) on MRI and amyloid-beta (Abeta) PET. A total
      of 471 cognitively impaired patients and 243 cognitively normal (CN) individuals
      were included in this study. Compared with CN individuals, cognitively impaired
      patients had a greater frequency of DELC (OR 1.6, 95% CI 1.1-2.2, P = 0.007).
      This relationship was more prominent in patients with dementia (OR 1.8, 95% CI
      1.2-2.7, P = 0.002) and subcortical vascular cognitive impairment (OR 2.4, 95% CI
      1.6-3.6, P < 0.001). Compared with Abeta-negative cognitively impaired patients
      with minimal WMH, Abeta-positive patients with moderate to severe WMH were
      significantly more likely to exhibit DELC (OR 7.3, 95% CI 3.4-16.0, P < 0.001).
      We suggest that DELC can serve as a useful supportive sign, not only for the
      presence of cognitive impairment, but also for cerebral small vessel disease
      (CSVD) and Abeta-positivity. The relationship between DELC and Abeta-positivity
      might be explained by the causative role of CSVD in Abeta accumulation.

PMID- 29042574
TI  - Size Variation under Domestication: Conservatism in the inner ear shape of
      wolves, dogs and dingoes.
AB  - A broad sample of wolves, dingoes, and domesticated dogs of different kinds and
      time periods was used to identify changes in size and shape of the organs of
      balance and hearing related to domestication and to evaluate the potential
      utility of uncovered patterns as markers of domestication. Using geometric
      morphometrics coupled with non-invasive imaging and three-dimensional
      reconstructions, we exposed and compared complex structures that remain largely
      conserved. There is no statistically significant difference in the levels of
      shape variation between prehistoric and modern dogs. Shape variance is slightly
      higher for the different components of the inner ear in modern dogs than in
      wolves, but these differences are not significant. Wolves express a significantly
      greater level of variance in the angle between the lateral and the posterior
      canal than domestic dog breeds. Wolves have smaller levels of size variation than
      dogs. In terms of the shape of the semicircular canals, dingoes reflect the mean
      shape in the context of variation in the sample. This mirrors the condition of
      feral forms in other organs, in which there is an incomplete return to the
      characteristics of the ancestor. In general, morphological diversity or disparity
      in the inner ear is generated by scaling.

PMID- 29042575
TI  - Role of the Qinghai-Tibetan Plateau uplift in the Northern Hemisphere
      disjunction: evidence from two herbaceous genera of Rubiaceae.
AB  - To assess the role of the Qinghai-Tibetan Plateau uplift in shaping the
      intercontinental disjunction in Northern Hemisphere, we analyzed the origin and
      diversification within a geological timeframe for two relict herbaceous genera,
      Theligonum and Kelloggia (Rubiaceae). Phylogenetic relationships within and
      between Theligonum and Kelloggia as well as their relatives were inferred using
      five chloroplast markers with parsimony, Bayesian and maximum-likelihood
      approaches. Migration routes and evolution of these taxa were reconstructed using
      Bayesian relaxed molecular clock and ancestral area reconstruction. Our results
      suggest the monophyly of each Theligonum and Kelloggia. Eastern Asian and North
      American species of Kelloggia diverged at ca.18.52 Mya and the Mediterranean
      species of Theligonum diverged from eastern Asian taxa at ca.13.73 Mya. Both
      Kelloggia and Theligonum are Tethyan flora relicts, and their ancestors might
      have been occurred in warm tropical to subtropical environments along the Tethys
      coast. The Qinghai-Tibetan Plateau separated the eastern and western Tethyan area
      may contribute significantly to the disjunct distributions of Theligonum, and the
      North Atlantic migration appears to be the most likely pathway of expansion of
      Kelloggia to North America. Our results highlight the importance role of the QTP
      uplift together with corresponding geological and climatic events in shaping
      biodiversity and biogeographic distribution in the Northern Hemisphere.

PMID- 29042576
TI  - Knot Energy, Complexity, and Mobility of Knotted Polymers.
AB  - The Coulomb energy E C is defined by the energy required to charge a conductive
      object and scales inversely to the self-capacity C, a basic measure of object
      size and shape. It is known that C is minimized for a sphere for all objects
      having the same volume, and that C increases as the symmetry of an object is
      reduced at fixed volume. Mathematically similar energy functionals have been
      related to the average knot crossing number <m>, a natural measure of knot
      complexity and, correspondingly, we find E C to be directly related to <m> of
      knotted DNA. To establish this relation, we employ molecular dynamics simulations
      to generate knotted polymeric configurations having different length and
      stiffness, and minimum knot crossing number values m for a wide class of knot
      types relevant to the real DNA. We then compute E C for all these knotted
      polymers using the program ZENO and find that the average Coulomb energy <E C> is
      directly proportional to <m>. Finally, we calculate estimates of the ratio of the
      hydrodynamic radius, radius of gyration, and the intrinsic viscosity of semi
      flexible knotted polymers in comparison to the linear polymeric chains since
      these ratios should be useful in characterizing knotted polymers experimentally.

PMID- 29042577
TI  - Dual-source Computed Tomography for Evaluating Pulmonary Artery and Aorta in
      Pediatric Patients with Single Ventricle.
AB  - To explore the accuracy of main pulmonary artery (MPA) and ascending aorta (AAO)
      image evaluation in pediatric patients with single ventricle (SV) by comparing
      dual-source computed tomography (DSCT) with echocardiography. Thirty-one children
      with SV were retrospectively enrolled. The stenosis, dilation, and location of
      MPA and AAO were independently evaluated by DSCT and echocardiography. The
      accompanying arterial malformations were also assessed by DSCT. For 17 patients
      undergoing cardiac catheterization, the DSCT-based diameters of MPA and AAO were
      correlated with their pressures as measured by catheterization. Referring to the
      surgical and catheterization findings, DSCT had better diagnostic performance in
      detecting the stenosis, dilation, and location of MPA and AAO with higher
      sensitivity than echocardiography (sensitivity, MPA: 88.0% vs. 80.0%, AAO: 100%
      vs. 66.7%, great arteries location: 95.7% vs. 95.2%). The correlations between
      diameters of MPA and AAO with their pressures were 0.399 (p = 0.04) and 0.611 (p
      = 0.01), respectively. In addition, DSCT detected 23 cases with patent ductus
      arteriosus, 26 systemic-to-pulmonary collaterals, 9 branch pulmonary distortions,
      and 4 coronary artery anomalies. DSCT is reliable for assessing the anatomic
      features of pulmonary artery and aorta in SV children, and provides comprehensive
      information for surgical strategy-making.

PMID- 29042579
TI  - Publisher Correction: Migratory appendicular muscles precursor cells in the
      common ancestor to all vertebrates.
AB  - In Fig. 2 of this Article originally published, some erroneous lines appeared on
      the left side of the images in panels c, e and g. The figure should have appeared
      as shown below. These errors have now been corrected in all versions of the
      Article.

PMID- 29042578
TI  - beta-defensin 1 expression in HCV infected liver/liver cancer: an important role
      in protecting HCV progression and liver cancer development.
AB  - beta-defensin family plays a role in host defense against viral infection,
      however its role in HCV infection is still unknown. In this study, we
      demonstrated that beta-defensin 1 was significantly reduced in HCV-infected liver
      specimens. Treatment with interferon and ribavirin upregulated beta-defensin-1,
      but not other beta-defensin tested, with the extent and duration of upregulation
      associated with treatment response. We investigated beta-defensin family
      expression in liver cancer in publicly available datasets and found that among
      all the beta-defensins tested, only beta-defensin 1 was significantly
      downregulated, suggesting beta-defensin 1 plays a crucial role in liver cancer
      development. Further analysis identified E-cadherin as the top positive
      correlated gene, while hepatocyte growth factor-regulated tyrosine kinase
      substrate as the top negative correlated gene. Expression of two proteoglycans
      were also positively correlated with that of beta-defensin 1. We have also
      identified small molecules as potential therapeutic agents to reverse beta
      defensin 1-associated gene signature. Furthermore, the downregulation of beta
      defensin 1 and E-cadherin, and upregulation of hepatocyte growth factor-regulated
      tyrosine kinase substrate, were further confirmed in liver cancer and adjacent
      normal tissue collected from in-house Chinese liver cancer patients. Together,
      our results suggest beta-defensin 1 plays an important role in protecting HCV
      progression and liver cancer development.

PMID- 29042580
TI  - Distorting temporal fine structure by phase shifting and its effects on speech
      intelligibility and neural phase locking.
AB  - Envelope (E) and temporal fine structure (TFS) are important features of acoustic
      signals and their corresponding perceptual function has been investigated with
      various listening tasks. To further understand the underlying neural processing
      of TFS, experiments in humans and animals were conducted to demonstrate the
      effects of modifying the TFS in natural speech sentences on both speech
      recognition and neural coding. The TFS of natural speech sentences was modified
      by distorting the phase and maintaining the magnitude. Speech intelligibility was
      then tested for normal-hearing listeners using the intact and reconstructed
      sentences presented in quiet and against background noise. Sentences with
      modified TFS were then used to evoke neural activity in auditory neurons of the
      inferior colliculus in guinea pigs. Our study demonstrated that speech
      intelligibility in humans relied on the periodic cues of speech TFS in both quiet
      and noisy listening conditions. Furthermore, recordings of neural activity from
      the guinea pig inferior colliculus have shown that individual auditory neurons
      exhibit phase locking patterns to the periodic cues of speech TFS that disappear
      when reconstructed sounds do not show periodic patterns anymore. Thus, the
      periodic cues of TFS are essential for speech intelligibility and are encoded in
      auditory neurons by phase locking.

PMID- 29042581
TI  - Immunoproteasome subunit beta5i/LMP7-deficiency in atherosclerosis.
AB  - Management of protein homeostasis by the ubiquitin-proteasome system is critical
      for atherosclerosis development. Recent studies showed controversial results on
      the role of immunoproteasome (IP) subunit beta5i/LMP7 in maintenance of protein
      homeostasis under cytokine induced oxidative stress. The present study aimed to
      investigate the effect of beta5i/LMP7-deficiency on the initiation and
      progression of atherosclerosis as a chronic inflammatory, immune cell driven
      disease. LDLR-/-LMP7-/- and LDLR-/- mice were fed a Western-type diet for either
      6 or 24 weeks to induce early and advanced stage atherosclerosis, respectively.
      Lesion burden was similar between genotypes in both stages. Macrophage content
      and abundance of polyubiquitin conjugates in aortic root plaques were unaltered
      by beta5i/LMP7-deficiency. In vitro experiments using bone marrow-derived
      macrophages (BMDM) showed that beta5i/LMP7-deficiency did not influence
      macrophage polarization or accumulation of polyubiquitinated proteins and cell
      survival upon hydrogen peroxide and interferon-gamma treatment. Analyses of
      proteasome core particle composition by Western blot revealed incorporation of
      standard proteasome subunits in beta5i/LMP7-deficient BMDM and spleen.
      Chymotrypsin-, trypsin- and caspase-like activities assessed by using short
      fluorogenic peptides in BMDM whole cell lysates were similar in both genotypes.
      Taken together, deficiency of IP subunit beta5i/LMP7 does not disturb protein
      homeostasis and does not aggravate atherogenesis in LDLR-/- mice.

PMID- 29042582
TI  - Portable biosensor for monitoring cortisol in low-volume perspired human sweat.
AB  - A non-faradaic label-free cortisol biosensor was demonstrated using MoS2
      nanosheets integrated into a nanoporous flexible electrode system. Low volume (1
      5 MUL) sensing was achieved through use of a novel sensor stack design comprised
      of vertically aligned metal electrodes confining semi-conductive MoS2 nanosheets.
      The MoS2 nanosheets were surface functionalized with cortisol antibodies towards
      developing an affinity biosensor specific to the physiological relevant range of
      cortisol (8.16 to 141.7 ng/mL) in perspired human sweat. Sensing was achieved by
      measuring impedance changes associated with cortisol binding along the MoS2
      nanosheet interface using electrochemical impedance spectroscopy. The sensor
      demonstrated a dynamic range from 1-500 ng/mL with a limit of detection of 1
      ng/mL. A specificity study was conducted using a metabolite expressed in human
      sweat, Ethyl Glucuronide. Continuous dosing studies were performed during which
      the sensor was able to discriminate between four cortisol concentration ranges
      (0.5, 5, 50, 500 ng/mL) for a 3+ hour duration. Translatability of the sensor was
      shown with a portable form factor device, demonstrating a comparable dynamic
      range and limit of detection for the sensor. The device demonstrated a R2
      correlation value of 0.998 when comparing measurements to the reported impedance
      values of the benchtop instrumentation.

PMID- 29042583
TI  - Prokaryotic Community Distribution along an Ecological Gradient of Salinity in
      Surface and Subsurface Saline Soils.
AB  - Salinity effects on microbial communities in saline soils is still unclear, and
      little is known about subsurface soil microbial communities especially in saline
      or hypersaline ecosystems. Here we presented the survey of the prokaryotic
      community in saline soils along a salinity gradient (17.3-148.3 dS/m) in surface
      (0-10 cm) and subsurface (15-30 cm) saline soils of Qarhan Salt Lake, China.
      Moreover, we compared them with three paired nonsaline normal soils. Using the
      high-throughput sequencing technology and several statistical methods, we
      observed no significant community difference between surface soils and subsurface
      soils. For environmental factors, we found that TOC was the primary driver of the
      prokaryotic community distribution in surface saline soils, so was pH in
      subsurface saline soils. Salinity had more effects on the prokaryotic community
      in subsurface saline soils than in surface saline soils and played a less
      important role in saline soils than in saline waters or saline sediments. Our
      research provided references for the prokaryotic community distribution along a
      salinity gradient in both surface and subsurface saline soils of arid playa
      areas.

PMID- 29042585
TI  - Compact-Morphology-based poly-metallic Nodule Delineation.
AB  - Poly-metallic nodules are a marine resource considered for deep sea mining.
      Assessing nodule abundance is of interest for mining companies and to monitor
      potential environmental impact. Optical seafloor imaging allows quantifying poly
      metallic nodule abundance at spatial scales from centimetres to square
      kilometres. Towed cameras and diving robots acquire high-resolution imagery that
      allow detecting individual nodules and measure their sizes. Spatial abundance
      statistics can be computed from these size measurements, providing e.g. seafloor
      coverage in percent and the nodule size distribution. Detecting nodules requires
      segmentation of nodule pixels from pixels showing sediment background. Semi
      supervised pattern recognition has been proposed to automate this task. Existing
      nodule segmentation algorithms employ machine learning that trains a classifier
      to segment the nodules in a high-dimensional feature space. Here, a rapid nodule
      segmentation algorithm is presented. It omits computation-intense feature-based
      classification and employs image processing only. It exploits a nodule
      compactness heuristic to delineate individual nodules. Complex machine learning
      methods are avoided to keep the algorithm simple and fast. The algorithm has
      successfully been applied to different image datasets. These data sets were
      acquired by different cameras, camera platforms and in varying illumination
      conditions. Their successful analysis shows the broad applicability of the
      proposed method.

PMID- 29042584
TI  - The Role of Chromatin Density in Cell Population Heterogeneity during Stem Cell
      Differentiation.
AB  - We incorporate three-dimensional (3D) conformation of chromosome (Hi-C) and
      single-cell RNA sequencing data together with discrete stochastic simulation, to
      explore the role of chromatin reorganization in determining gene expression
      heterogeneity during development. While previous research has emphasized the
      importance of chromatin architecture on activation and suppression of certain
      regulatory genes and gene networks, our study demonstrates how chromatin
      remodeling can dictate gene expression distribution by folding into distinct
      topological domains. We hypothesize that the local DNA density during
      differentiation accentuate transcriptional bursting due to the crowding effect of
      chromatin. This phenomenon yields a heterogeneous cell population, thereby
      increasing the potential of differentiation of the stem cells.

PMID- 29042586
TI  - Bone Microarchitecture and Biomechanics of the Necrotic Femoral Head.
AB  - The mechanism behind osteonecrosis of the femoral head (ONFH) remains unclear.
      The aim of this study was to explore the pathogenesis of ONFH from a
      biomechanical standpoint to provide a theoretical basis for improved treatments.
      We compared the bone structure of fractured femoral heads with that of necrotic
      femoral heads by Micro-CT scanning and histological evaluation. In addition, we
      compared the biomechanical properties of each zone in fractured femoral heads
      with those in necrotic femoral heads by using biomechanical tests. Compared with
      fractured femoral heads, bone microarchitecture and bone morphometry in necrotic
      zone and sclerotic zone of necrotic femoral heads have altered markedly. In
      addition, the biomechanical properties of the necrotic zone in femoral heads
      weaken markedly, while those of the sclerotic zone strengthen. We hypothesize
      that discordance between bone structure and function of the femoral head may be
      involved in the pathogenesis of ONFH and that more attention should be paid to
      the prevention and treatment of such discordance.

PMID- 29042587
TI  - MiR-302b Suppresses Osteosarcoma Cell Migration and Invasion by Targeting Runx2.
AB  - Osteosarcoma patients with lung metastasis and local invasion remain challenging
      to treat despite the significant contribution of the combination of surgery and
      neo-adjuvant chemotherapy. Our previous microarray study demonstrated that miR
      302b had significantly lower expression in osteosarcoma cell lines than in
      osteoblast cell lines. In the present study, we further elucidated the role of
      miR-302b in regulating the migration and invasiveness of osteosarcoma. MiR-302b
      expression was markedly down-regulated in osteosarcoma cell lines and clinical
      tumour tissues. Lower levels of miR-302b expression were significantly associated
      with metastasis and high pathological grades. A functional study demonstrated
      that over-expression of miR-302b suppressed tumour cell proliferation, invasion
      and migration in vitro and in vivo. Runx2 was identified as a direct target gene
      for miR-302b by bioinformatics analysis and dual-luciferase reporter gene assay.
      Moreover, over-expression of miR-302b induced down-regulation of Runx2, OPN, MMP
      2, MMP-9, MMP-12, MMP-14, and VEGF in 143B cells. Exogenous expression of Runx2
      partially rescued the inhibitory effect of miR-302b on the invasion and migration
      activity of 143B osteosarcoma cells. Taken together, our results indicate that
      miR-302b functions as a tumour repressor in the invasion and migration of
      osteosarcoma by directly downregulating Runx2 expression and may be a potential
      therapeutic target for osteosarcoma.

PMID- 29042588
TI  - A Microscopic Shell Structure with Schwarz's D-Surface.
AB  - Recently, materials with micro-architecture of hollow trusses and ultralow
      density (less than 10-2 Mg/m3) have gained attention. The materials have been
      fabricated by forming templates based on 3D lithographical techniques, followed
      by hard coating on the surface, and finally etching out the template. Here, we
      describe a novel fabrication method for another micro architecture composed of a
      single continuous smooth-curved shell with D-surface, named Shellular; its
      template is prepared based on weaving flexible polymer wires. Compression test
      results reveal that these D-surfaced Shellulars have strength and Young's modulus
      comparable to those of their hollow truss-based competitors. The best virtue of
      this weaving-based technology is its mass-productivity and large-size potential.
      Also, this technology can be applied to fabricate not only D-surfaced but also P-
      or G-surfaced Shellular. The unique geometry of Shellular, composed of a single
      continuous, smooth, and interfacial shell or membrane separating two equivalent
      sub-volumes intertwined with each other, appears to possess huge application
      potential such as non-clogging tissue engineering scaffolds and compact light
      weight fuel cells with high energy density.

PMID- 29042589
TI  - GLRB variants regulate nearby gene expression in human brain tissues.
AB  - A recent genome-wide association study (GWAS) identified four genetic variants
      rs78726293, rs191260602, rs17035816 and rs7688285 in GLRB gene to be associated
      with panic disorder (PD) risk. In fact, GWAS is an important first step to
      investigate the genetics of human complex diseases. In order to translate into
      opportunities for new diagnostics and therapies, we must identify the genes
      perturbed by these four variants, and understand how these variant functionally
      contributes to the underlying disease pathogenesis. Here, we investigated the
      effect of these four genetic variants and the expression of three nearby genes
      including PDGFC, GLRB and GRIA2 in human brain tissues using the GTEx (version 6)
      and Braineac eQTLs datasets. In GTEx (version 6) dataset, the results showed that
      both rs17035816 and rs7688285 variants could significantly regulate PDGFC and
      GLRB gene expression. In Braineac dataset, the results showed that rs17035816
      variant could significantly regulate GLRB and GRIA2 gene expression. We believe
      that these findings further provide important supplementary information about the
      regulating mechanisms of rs17035816 and rs7688285 variants in PD risk.

PMID- 29042590
TI  - Effects of short-term heat shock and physiological responses to heat stress in
      two Bradysia adults, Bradysia odoriphaga and Bradysia difformis.
AB  - Bradysia odoriphaga and Bradysia difformis are devastating pests of vegetable,
      ornamental crops and edible mushrooms causing significant losses. Temperature may
      be an important factor restricting their population abundance in the summer. To
      determine the effects of short-term heat shock on adults, their survival,
      longevity and fecundity data were collected, and antioxidant responses and heat
      shock protein expression levels were examined. Our results indicated that the
      survival rates of Bradysia adults decreased rapidly after heat shock >=36 
      degrees C, and the longevity and reproductive capacities were significantly
      inhibited, indicating that short-term heat shock had lethal and sub-lethal
      effects. Moreover, the lipid peroxidation levels of B. difformis and B.
      odoriphaga increased dramatically at 36  degrees C and 38  degrees C,
      respectively. Four antioxidant enzymes activities of B. odoriphaga were greater
      than those of B. difformis at 38  degrees C. Additionally, hsp70 and hsp90
      expression levels significantly increased after heat stress, and higher
      expression levels of B. difformis and B. odoriphaga were discovered at 36 and 38 
      degrees C respectively, indicating their different heat tolerance levels.
      Overall, short-term heat shock (>=36  degrees C) caused significantly adverse
      effects on Bradysia adults, indicating that it could be applied in pest control,
      and antioxidant system and hsp genes played important roles in their heat
      tolerance levels.

PMID- 29042591
TI  - Diffusion and distribution of deuterium in scandium deuteride thin films under
      irradiation of deuterium ion beam.
AB  - Scandium deuteride (ScDx) thin films, as an alternative target for deuterium
      deuterium (D-D) reaction, are a very important candidate for detection and
      diagnostic applications. Albeit with their superior thermal stability, the
      ignorance of the stability of ScDx under irradiation of deuterium ion beam
      hinders the realization of their full potential. In this report, we characterize
      ScDx thin films with scanning electron microscopy (SEM) and X-ray diffraction
      (XRD), Rutherford backscattering spectroscopy (RBS) and elastic recoil detection
      analysis (ERDA). We found with increased implantation of deuterium ions,
      accumulation and diffusion of deuterium are enhanced. Surprisingly, the
      concentration of deuterium restored to the value before implantation even at room
      temperature, revealing a self-healing process which is of great importance for
      the long-term operation of neutron generator.

PMID- 29042593
TI  - Structure, Intrinsic properties and Vibrational Spectra of Pr(Mg1/2Sn1/2)O3
      Ceramic Crystal.
AB  - Pr(Mg1/2Sn1/2)O3 (PMS) ceramic was prepared through a conventional solid-state
      reaction method. Crystal structure was investigated through X-ray diffraction
      (XRD), which certificates that the main phase is PMS with monoclinic P2 1/n1
      symmetry. Lattice vibrational modes were obtained through Raman scattering
      spectroscopy and Fourier transform far-infrared reflection spectroscopy. The
      Raman spectrum active modes were assigned and illustrated, respectively, and then
      fitted with Lorentzian function. The four modes within the range of 110-200 cm-1
      are derived from the F 2g vibrations (A-site cations), and the other three modes
      (300-430 cm-1) are derived from the F 2g vibrations (B-site cations).The mode
      with highest frequency above 650 cm-1 is attributed to A 1g -like mode that
      corresponds to the symmetric breathing of oxygen octahedral. The far-infrared
      spectrum with seven infrared active modes was fitted using four-parameter semi
      quantum models to calculate intrinsic properties (permittivity and loss). F 2u(2)
      yielded the greatest contribution to dielectric constant and loss, which is
      mainly performed as the inverted translational vibration of Pr-MgO6 octahedron.

PMID- 29042592
TI  - Impaired detection of happy facial expressions in autism.
AB  - The detection of emotional facial expressions plays an indispensable role in
      social interaction. Psychological studies have shown that typically developing
      (TD) individuals more rapidly detect emotional expressions than neutral
      expressions. However, it remains unclear whether individuals with autistic
      phenotypes, such as autism spectrum disorder (ASD) and high levels of autistic
      traits (ATs), are impaired in this ability. We examined this by comparing TD and
      ASD individuals in Experiment 1 and individuals with low and high ATs in
      Experiment 2 using the visual search paradigm. Participants detected normal
      facial expressions of anger and happiness and their anti-expressions within
      crowds of neutral expressions. In Experiment 1, reaction times were shorter for
      normal angry expressions than for anti-expressions in both TD and ASD groups.
      This was also the case for normal happy expressions vs. anti-expressions in the
      TD group but not in the ASD group. Similarly, in Experiment 2, the detection of
      normal vs. anti-expressions was faster for angry expressions in both groups and
      for happy expressions in the low, but not high, ATs group. These results suggest
      that the detection of happy facial expressions is impaired in individuals with
      ASD and high ATs, which may contribute to their difficulty in creating and
      maintaining affiliative social relationships.

PMID- 29042594
TI  - Serum SAA1 and APOE are novel indicators for human cytomegalovirus infection.
AB  - Human cytomegalovirus (HCMV) infection is a global concern and highly infectious.
      HCMV-infected individuals are often carriers with damaged immunity. However few
      diagnostic indicators block HMCV control and prevention. Thus, we measured 21
      serum proteins related to HCMV infection using iTRAQ-labeling based quantitative
      proteomic approaches and SAA1 and APOE were confirmed as candidate serum
      indicators for identification of HMCV infection according to ROC curve analysis
      and that co-occurrence of SAA1 and APOE are better markers than individual
      proteins.

PMID- 29042595
TI  - A plasma proteomics method reveals links between ischemic stroke and MTHFR C677T
      genotype.
AB  - Methylene Tetrahydrofolate Reductase (MTHFR) catalyzes the conversion of
      methylene tetrahydrofolate to methylte trahydrofolate. The 677th nucleotide of
      the MTHFR gene is often regarded as a risk factor of cardiovascular disease.
      Previous studies demonstrated an elevated risk of ischemic stroke with the
      MTHFR677TT genotype. In this study, we employed a plasma proteomics method to
      investigate the connection between the polymorphism of the target nucleotide and
      stroke. In total, 28 protein spots were differentially expressed between the two
      groups, and of which, 25 protein spots were up-regulated and 3 were down
      regulated. Five randomly selected spots were successfully identified as
      Haptoglobin (HPT) and Transferrin (TRFE). A functional analysis indicated that
      most of the differential expressed proteins (DEPs) were related to the
      inflammatory immune response. A Kyoto Encyclopedia of Genes and Genomes (KEGG)
      pathway analysis showed that these DEPs were involved in the complement cascade
      reaction. Meanwhile, protein-protein interactions (PPIs) analysis highlighted the
      novel association between the C677T MTHFR genotype and Vitamin D binding protein
      (DBP), which was confirmed by a molecular genetic analysis. The results suggested
      that the phenotype of the MTHFR might be associated with multiple proteins that
      have a synergistic effect, which might be related to the mechanism of ischemic
      stroke.

PMID- 29042596
TI  - Host heterozygosity and genotype rarity affect viral dynamics in an avian
      subspecies complex.
AB  - Genetic diversity at community, population and individual levels is thought to
      influence the spread of infectious disease. At the individual level, inbreeding
      and heterozygosity are associated with increased risk of infection and disease
      severity. Host genotype rarity may also reduce infection risk if pathogens are co
      adapted to common or local hosts, but to date, no studies have investigated the
      relative importance of genotype rarity and heterozygosity for infection in a
      wild, sexually reproducing vertebrate. With beak and feather disease virus (BFDV)
      infection in a wild parrot (Platycercus elegans), we show that both
      heterozygosity and genotype rarity of individual hosts predicted infection, but
      in contrasting ways. Heterozygosity was negatively associated with probability of
      infection, but not with infection load. In contrast, increased host genotype
      rarity was associated with lower viral load in infected individuals, but did not
      predict infection probability. These effects were largely consistent across
      subspecies, but were not evident at the population level. Subspecies and age were
      also strongly associated with infection. Our study provides novel insights into
      infection dynamics by quantifying rarity and diversity simultaneously. We
      elucidate roles that host genetic diversity can play in infection dynamics, with
      implications for understanding population divergence, intraspecific diversity and
      conservation.

PMID- 29042598
TI  - A generalized simulation development approach for predicting refugee
      destinations.
AB  - In recent years, global forced displacement has reached record levels, with 22.5
      million refugees worldwide. Forecasting refugee movements is important, as
      accurate predictions can help save refugee lives by allowing governments and NGOs
      to conduct a better informed allocation of humanitarian resources. Here, we
      propose a generalized simulation development approach to predict the destinations
      of refugee movements in conflict regions. In this approach, we synthesize data
      from UNHCR, ACLED and Bing Maps to construct agent-based simulations of refugee
      movements. We apply our approach to develop, run and validate refugee movement
      simulations set in three major African conflicts, estimating the distribution of
      incoming refugees across destination camps, given the expected total number of
      refugees in the conflict. Our simulations consistently predict more than 75% of
      the refugee destinations correctly after the first 12 days, and consistently
      outperform alternative naive forecasting techniques. Using our approach, we are
      also able to reproduce key trends in refugee arrival rates found in the UNHCR
      data.

PMID- 29042597
TI  - Herpud1 negatively regulates pathological cardiac hypertrophy by inducing IP3
      receptor degradation.
AB  - Cardiac hypertrophy is an adaptive response triggered by pathological stimuli.
      Regulation of the synthesis and the degradation of the Ca2+ channel inositol
      1,4,5-trisphosphate receptor (IP3R) affects progression to cardiac hypertrophy.
      Herpud1, a component of the endoplasmic reticulum-associated degradation (ERAD)
      complex, participates in IP3R1 degradation and Ca2+ signaling, but the cardiac
      function of Herpud1 remains unknown. We hypothesize that Herpud1 acts as a
      negative regulator of cardiac hypertrophy by regulating IP3R protein levels. Our
      results show that Herpud1-knockout mice exhibit cardiac hypertrophy and
      dysfunction and that decreased Herpud1 protein levels lead to elevated levels of
      hypertrophic markers in cultured rat cardiomyocytes. In addition, IP3R levels
      were elevated both in Herpud1-knockout mice and Herpud1 siRNA-treated rat
      cardiomyocytes. The latter treatment also led to elevated cytosolic and nuclear
      Ca2+ levels. In summary, the absence of Herpud1 generates a pathological
      hypertrophic phenotype by regulating IP3R protein levels. Herpud1 is a novel
      negative regulator of pathological cardiac hypertrophy.

PMID- 29042599
TI  - Progesterone Via its Type-A Receptor Promotes Myometrial Gap Junction Coupling.
AB  - Effective labour contractions require synchronization of myometrial cells through
      gap junctions (GJs). Clasically, progesterone (P4) is known to inhibit the
      expression of connexin-43 (Cx43, major component of GJs) and GJ formation in
      myometrium. Our current study is based on a striking observation that challenges
      this dogma. We observed conspicuous differences in the intracellular localization
      of Cx43 protein in PRA versus PRB expressing myocytes. Thus in P4 stimulated PRA
      cells Cx43 protein forms GJs, whereas in PRB cells the forward trafficking of
      Cx43 and GJ formation is inhibited even when Cx43 is overexpressed. We found that
      P4, via PRA/B, differentially regulates Cx43 translation to generate a Cx43-20 K
      isoform, which facilitates the transport of full length Cx43 to plasma membrane.
      The P4 mediated regulation of Cx43 trafficking and GJ formation occurs via non
      genomic pathway and involves the regulation of mTOR signaling since inhibition of
      this pathway restored the Cx43 trafficking defect in PRB cells. We propose that
      PRA is a master regulator of Cx43 expression, GJ formation and myocyte
      connectivity/synchronization for labour.

PMID- 29042601
TI  - Short-term effects of tillage and residue on spring maize yield through
      regulating root-shoot ratio in Northeast China.
AB  - In recent years, yield instability of spring maize becomes increasingly
      pronounced under the traditional cropping system. In 2014 and 2015, short-term
      effects of tillage (plow-till, rotary-till and no-till) and residue (removal and
      incorporation) on soil properties, maize growth and yield were investigated in a
      brown soil region. Our results indicated that short-term reduced tillage (rotary
      till and no-till) and residue incorporation promoted soil properties and maize
      growth. Compared with plow-till, rotary-till and no-till decreased soil bulk
      density and compaction below the plough layer (~30 cm). The soil organic carbon
      (SOC), total nitrogen and C:N of surface soil layers increased under the rotary
      till (0-20 cm) and no-till (0-10 cm), which were higher in 0-30 cm soil layers
      for residue incorporation. For both years, root characteristics of root diameter
      (RAD) and root surface area density (RSD), biomass indexes of root biomass (RB),
      shoot biomass (SB) and root-shoot ratio (R:S) were increased under these short
      term treatments. Although there were positive relationships between soil water
      content (SWC), C:N, RAD, RSD, RB, SB, R:S and yield, structural equation modeling
      showed maize yield was directly controlled by R:S. These findings will have
      important implications for improving the current cropping system (i.e., plow-till
      with residue removed) in this area.

PMID- 29042600
TI  - Dynamic and Modularized MicroRNA Regulation and Its Implication in Human Cancers.
AB  - MicroRNA is responsible for the fine-tuning of fundamental cellular activities
      and human disease development. The altered availability of microRNAs, target
      mRNAs, and other types of endogenous RNAs competing for microRNA interactions
      reflects the dynamic and conditional property of microRNA-mediated gene
      regulation that remains under-investigated. Here we propose a new integrative
      method to study this dynamic process by considering both competing and
      cooperative mechanisms and identifying functional modules where different
      microRNAs co-regulate the same functional process. Specifically, a new pipeline
      was built based on a meta-Lasso regression model and the proof-of-concept study
      was performed using a large-scale genomic dataset from ~4,200 patients with 9
      cancer types. In the analysis, 10,726 microRNA-mRNA interactions were identified
      to be associated with a specific stage and/or type of cancer, which demonstrated
      the dynamic and conditional miRNA regulation during cancer progression. On the
      other hands, we detected 4,134 regulatory modules that exhibit high fidelity of
      microRNA function through selective microRNA-mRNA binding and modulation. For
      example, miR-18a-3p, -320a, -193b-3p, and -92b-3p co-regulate the
      glycolysis/gluconeogenesis and focal adhesion in cancers of kidney, liver, lung,
      and uterus. Furthermore, several new insights into dynamic microRNA regulation in
      cancers have been discovered in this study.

PMID- 29042602
TI  - The optimal window size for analysing longitudinal networks.
AB  - The time interval between two snapshots is referred to as the window size. A
      given longitudinal network can be analysed from various actor-level perspectives,
      such as exploring how actors change their degree centrality values or
      participation statistics over time. Determining the optimal window size for the
      analysis of a given longitudinal network from different actor-level perspectives
      is a well-researched network science problem. Many researchers have attempted to
      develop a solution to this problem by considering different approaches; however,
      to date, no comprehensive and well-acknowledged solution that can be applied to
      various longitudinal networks has been found. We propose a novel approach to this
      problem that involves determining the correct window size when a given
      longitudinal network is analysed from different actor-level perspectives. The
      approach is based on the concept of actor-level dynamicity, which captures
      variability in the structural behaviours of actors in a given longitudinal
      network. The approach is applied to four real-world, variable-sized longitudinal
      networks to determine their optimal window sizes. The optimal window length for
      each network, determined using the approach proposed in this paper, is further
      evaluated via time series and data mining methods to validate its optimality.
      Implications of this approach are discussed in this article.

PMID- 29042603
TI  - Separation of Antioxidant Peptides from Pepsin Hydrolysate of Whey Protein
      Isolate by ATPS of EOPO Co-polymer (UCON)/Phosphate.
AB  - An aqueous two-phase system (ATPS) consisting of poly(ethylene glycol-ran
      propylene glycol) monobutyl ether (UCON)/phosphate was developed for the
      separation of the antioxidant peptides from pepsin hydrolysate of Whey Protein
      Isolate (WPI). The efficiency of the separation was evaluated based on the DPPH
      radical scavenging activity, ABTS radical scavenging activity and ferric reducing
      antioxidant power (FRAP) of the separated peptides. The effects of some
      parameters on the partition of antioxidant peptides were investigated. An
      efficient separation of antioxidant peptides was achieved using ATPS with pH of
      4.0, 4 mL of UCON solution (40%, w/w), 4 mL of KH2PO4 solution (15.5%, w/w), 2 mL
      of WPI hydrolysate and 0.40 g/10 mL of NaCl. Reversed-phase high-performance
      liquid chromatography (RP-HPLC), amino acid analyzer and matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used
      to characterize the purified peptides separated by the ATPS. The peptides in top
      phase were less polar than those in bottom phase. More antioxidative and
      hydrophobic amino acids were extracted to the top phase of ATPS, and the peptides
      with the amino acid sequences with antioxidant activities moved to the top phase
      as well. In conclusion, antioxidant peptides were successfully separated from the
      WPI hydrolysate by UCON/phosphate ATPS.

PMID- 29042605
TI  - Dynamic photo-switching in light-responsive JUC-62 for CO 2 capture.
AB  - In this paper, we demonstrate the highly efficient photo-switching ability of a
      Cu-azobenzene tetracarboxylate MOF (JUC-62) for low-energy CO2 capture. Under UV
      light irradiation, both at 273 and 298 K, JUC-62 showed 51% and 34% lower CO2
      uptake, respectively, than when UV light was off. Its dynamic CO2 uptake also
      matched well with its static condition. Storing it at ambient condition was also
      found not to destroy its framework structure and its dynamic photoswitching
      property could still be maintained.

PMID- 29042604
TI  - Placenta-specific1 (PLAC1) is a potential target for antibody-drug conjugate
      based prostate cancer immunotherapy.
AB  - Our recent findings strongly support the idea of PLAC1 being as a potential
      immunotherapeutic target in prostate cancer (PCa). Here, we have generated and
      evaluated an anti-placenta-specific1 (PLAC1)-based antibody drug conjugate (ADC)
      for targeted immunotherapy of PCa. Prostate cancer cells express considerable
      levels of PLAC1. The Anti-PLAC1 clone, 2H12C12, showed high reactivity with
      recombinant PLAC1 and selectivity recognized PLAC1 in prostate cancer cells but
      not in LS180 cells, the negative control. PLAC1 binding induced rapid
      internalization of the antibody within a few minutes which reached to about 50%
      after 15 min and almost completed within an hour. After SN38 conjugation to
      antibody, a drug-antibody ratio (DAR) of about 5.5 was achieved without apparent
      negative effect on antibody affinity to cell surface antigen. The ADC retained
      intrinsic antibody activity and showed enhanced and selective cytotoxicity with
      an IC50 of 62 nM which was about 15-fold lower compared to free drug. Anti-PLAC1
      ADC induced apoptosis in human primary prostate cancer cells and prostate cell
      lines. No apparent cytotoxic effect was observed in in vivo animal safety
      experiments. Our newly developed anti-PLAC1-based ADCs might pave the way for a
      reliable, efficient, and novel immunotherapeutic modality for patients with PCa.

PMID- 29042606
TI  - Population genomics of Wolbachia and mtDNA in Drosophila simulans from
      California.
AB  - Wolbachia pipientis is an intracellular endosymbiont infecting many arthropods
      and filarial nematodes. Little is known about the short-term evolution of
      Wolbachia or its interaction with its host. Wolbachia is maternally inherited,
      resulting in co-inheritance of mitochondrial organelles such as mtDNA. Here I
      explore the evolution of Wolbachia, and the relationship between Wolbachia and
      mtDNA, using a large inbred panel of Drosophila simulans. I compare this to the
      only other large population genomic Wolbachia dataset from D. melanogaster. I
      find reduced diversity relative to expectation in both Wolbachia and mtDNA, but
      only mtDNA shows evidence of a recent selective sweep or population bottleneck. I
      estimate Wolbachia and mtDNA titre in each genotype, and I find considerable
      variation in both phenotypes, despite low genetic diversity in Wolbachia and
      mtDNA. A phylogeny of Wolbachia and of mtDNA suggest a recent origin of the
      infection derived from a single origin. Using Wolbachia and mtDNA titre as a
      phenotype, I perform the first association analysis using this phenotype with the
      nuclear genome and find several implicated regions, including one which contains
      four CAAX-box protein processing genes. CAAX-box protein processing can be an
      important part of host-pathogen interactions in other systems, suggesting
      interesting directions for future research.

PMID- 29042607
TI  - Abnormal M1/M2 macrophage phenotype profiles in the small airway wall and lumen
      in smokers and chronic obstructive pulmonary disease (COPD).
AB  - We explore potential dysregulation of macrophage phenotypes in COPD pathogenesis
      through integrated study of human small airway tissue, bronchoalveolar lavage
      (BAL) and an experimental murine model of COPD. We evaluated human airway tissue
      and BAL from healthy controls, normal lung function smokers (NLFS), and COPD
      subjects. Both small airways and BAL cells were immunohistochemically stained
      with anti-CD68 for total macrophages and with anti-CD163 for M2, and anti-iNOS
      for M1 macrophages. Multiplex ELISA measured BAL cytokines. Comparable cigarette
      smoke-induced experimental COPD mouse model was assessed for relevant mRNA
      profiles. We found an increase in pro-inflammatory M1s in the small airways of
      NLFS and COPD compared to controls with a reciprocal decrease in M2 macrophages,
      which remained unchanged among pathological groups. However, luminal macrophages
      showed a dominant M2 phenotype in both NLFS and COPD subjects. BAL cytokine
      skewed towards an M2 profile with increase in CCL22, IL-4, IL-13, and IL-10 in
      both NLFS and COPDs. The mouse-model of COPD showed similar increase in mRNA for
      M2 markers. Our finding suggests abnormal macrophage switching in both mucosal
      and luminal areas of COPD patients, that strongly associated with cytokine
      balance. There may be potential for beneficial therapeutic cytokine manipulation
      of macrophage phenotypes in COPD.

PMID- 29042608
TI  - Sedum alfredii SaNramp6 Metal Transporter Contributes to Cadmium Accumulation in
      Transgenic Arabidopsis thaliana.
AB  - The plant natural resistance-associated macrophage protein (Nramp) family plays
      an important role in tolerance to heavy metal stress. However, few Nramps have
      been functionally characterized in the heavy metal-accumulating plant Sedum
      alfredii. Here, Nramp6 was cloned and identified from S. alfredii and its
      function analyzed in transgenic Arabidopsis thaliana. SaNramp6 cDNA contains an
      open reading frame of 1, 638 bp encoding 545 amino acids. SaNramp6's expression
      can be induced by cadmium (Cd) stress, and, after treatment, it peaked at one
      week and 12 h in the roots and leaves, respectively. SaNramp6 localized to the
      plasma membrane in protoplasts isolated from A. thaliana, Nicotiana benthamiana
      lower leaf and onion (Allium cepa) epidermal cells. The heterologous expression
      of SaNramp6 in the Deltaycf1 yeast mutant increased the Cd content in yeast
      cells. SaNramp6 also rescued the low Cd accumulation of the A. thaliana nramp1
      mutant. Transgenic A. thaliana expressing SaNramp6 exhibited high Cd accumulation
      levels, as determined by a statistical analysis of the Cd concentration,
      translocation factors and net Cd2+ fluxes under Cd stress. Thus, SaNramp6 may
      play a significant role in improving Cd accumulation, and the gene may be useful
      for the biotechnological development of transgenic plants for phytoremediation.

PMID- 29042609
TI  - Structural analysis of PIM1 kinase complexes with ATP-competitive inhibitors.
AB  - PIM1 is an oncogenic kinase overexpressed in a number of cancers where it
      correlates with poor prognosis. Several studies demonstrated that inhibition of
      PIM1 activity is an attractive strategy in fighting overexpressing cancers, while
      distinct structural features of ATP binding pocket make PIM1 an inviting target
      for the design of selective inhibitors. To facilitate development of specific
      PIM1 inhibitors, in this study we report three crystal structures of ATP
      competitive inhibitors at the ATP binding pocket of PIM1. Two of the reported
      structures (CX-4945 and Ro-3306) explain the off-target effect on PIM1 of
      respectively casein kinase 2 and cyclin-dependent kinase 1 dedicated inhibitors.
      In turn, the structure with CX-6258 demonstrates a binding mode of a potent,
      selective inhibitor of PIM1, PIM2, PIM3 and Flt-3 kinases. The consequences of
      our findings for future inhibitor development are discussed.

PMID- 29042610
TI  - Giant Enhancement of Exchange Coupling in Entropy-Stabilized Oxide
      Heterostructures.
AB  - Entropy-stabilized materials are stabilized by the configurational entropy of the
      constituents, rather than the enthalpy of formation of the compound. A unique
      benefit to entropy-stabilized materials is the increased solubility of elements,
      which opens a broad compositional space, with subsequent local chemical and
      structural disorder resulting from different atomic sizes and preferred
      coordinations of the constituents. Known entropy-stabilized oxides contain
      magnetically interesting constituents, however, the magnetic properties of the
      multi-component oxide have yet to be investigated. Here we examine the role of
      disorder and composition on the exchange anisotropy of permalloy/(Mg0.25(1
      x)CoxNi0.25(1-x)Cu0.25(1-x)Zn0.25(1-x))O heterostructures. Anisotropic magnetic
      exchange and the presence of a critical blocking temperature indicates that the
      magnetic order of the entropy-stabilized oxides considered here is
      antiferromagnetic. Changing the composition of the oxide tunes the disorder,
      exchange field and magnetic anisotropy. Here, we exploit this tunability to
      enhance the strength of the exchange field by a factor of 10x at low
      temperatures, when compared to a permalloy/CoO heterostructure. Significant
      deviations from the rule of mixtures are observed in the structural and magnetic
      parameters, indicating that the crystal is dominated by configurational entropy.
      Our results reveal that the unique characteristics of entropy-stabilized
      materials can be utilized and tailored to engineer magnetic functional phenomena
      in oxide thin films.

PMID- 29042611
TI  - Developmental stage-dependent regulation of spine formation by calcium-calmodulin
      dependent protein kinase IIalpha and Rap1.
AB  - The roles of calcium-calmodulin-dependent protein kinase II-alpha (CaMKIIalpha)
      in the expression of long-term synaptic plasticity in the adult brain have been
      extensively studied. However, how increased CaMKIIalpha activity controls the
      maturation of neuronal circuits remains incompletely understood. Herein, we show
      that pyramidal neurons without CaMKIIalpha activity upregulate the rate of spine
      addition, resulting in elevated spine density. Genetic elimination of CaMKIIalpha
      activity specifically eliminated the observed maturation-dependent suppression of
      spine formation. Enhanced spine formation was associated with the stabilization
      of actin in the spine and could be reversed by increasing the activity of the
      small GTPase Rap1. CaMKIIalpha activity was critical in the phosphorylation of
      synaptic Ras GTPase-activating protein (synGAP), the dispersion of synGAP from
      postsynaptic sites, and the activation of postsynaptic Rap1. CaMKIIalpha is
      already known to be essential in learning and memory, but our findings suggest
      that CaMKIIalpha plays an important activity-dependent role in restricting spine
      density during postnatal development.

PMID- 29042612
TI  - Novel Application of Magnetic Protein: Convenient One-Step Purification and
      Immobilization of Proteins.
AB  - Recently, a magnetic protein was discovered, and a multimeric magnetosensing
      complex was validated, which may form the basis of magnetoreception. In this
      study, the magnetic protein was firstly used in biotechnology application, and a
      novel convenient one-step purification and immobilization method was established.
      A universal vector and three linker patterns were developed for fusion expression
      of magnetic protein and target protein. The magnetic protein was absorbed by iron
      beads, followed by target protein aggregation, purification, and immobilization.
      GFP, employed as a reporter protein, was successfully purified from cell lysate.
      Subsequently, three enzymes (lipase, alpha-L-arabinofuranosidase, pullulanase)
      with different molecular sizes testified the versatility of this magnetic-based
      approach. The specific activities of the purified enzymes were distinctly higher
      than those of the traditionally purified enzymes using affinity chromatography.
      The lipase immobilized on iron beads presented improved thermostability and
      enhanced pH tolerance compared to the free enzyme. The immobilized lipase could
      be easily recovered and reused for maximum utilization. After 20 cycles of
      reutilization, the magnetically immobilized lipase retained 71% of its initial
      activity. This investigation may help introduce magnetic protein into
      biotechnology applications, and the one-step purification and immobilization
      method may serve to illustrate an economically viable process for industry.

PMID- 29042613
TI  - Fabrication of AO/LDH fluorescence composite and its detection of Hg2+ in water.
AB  - Divalent mercury ion (Hg2+) is one of the most common pollutants in water with
      high toxicity and significant bioaccumulation, for which sensitive and selective
      detection methods are highly necessary to carry out its detection and
      quantification. Fluorescence detection by organic dyes is a simple and rapid
      method in pollutant analyses and is limited because of quenching caused by
      aggregation dye molecules. Hydrotalcite (LDH) is one of the most excellent
      carrier materials. In this study, an organic dye acridine orange (AO) was
      successfully loaded on the LDH layers, which significantly inhibited fluorescence
      quenching of AO. The composite AO/LDH reaches the highest fluorescence intensity
      when the AO initial concentration is 5 mg/L. With its enhanced fluorescent
      property, the composite powder was fabricated to fluorescence test papers. The
      maximal fluorescence intensity was achieved with a pulp to AO/LDH ratio of 1:5
      which can be used to detect Hg2+ in water by naked eyes. Hg2+ in aqueous solution
      can be detected by instruments in the range of 0.5 to 150 mM. The novelty of this
      study lies on both the development of a new type of mineral-dye composite
      material, as well as its practical applications for fast detection.

PMID- 29042614
TI  - 3D- Printed Poly(epsilon-caprolactone) Scaffold Integrated with Cell-laden
      Chitosan Hydrogels for Bone Tissue Engineering.
AB  - Synthetic polymeric scaffolds are commonly used in bone tissue engineering (BTE)
      due to their biocompatibility and adequate mechanical properties. However, their
      hydrophobicity and the lack of specific cell recognition sites confined their
      practical application. In this study, to improve the cell seeding efficiency and
      osteoinductivity, an injectable thermo-sensitive chitosan hydrogel (CSG) was
      incorporated into a 3D-printed poly(epsilon-caprolactone) (PCL) scaffold to form
      a hybrid scaffold. To demonstrate the feasibility of this hybrid system for BTE
      application, rabbit bone marrow mesenchymal stem cells (BMMSCs) and bone
      morphogenetic protein-2 (BMP-2) were encapsulated in CSG. Pure PCL scaffolds were
      used as controls. Cell proliferation and viability were investigated. Osteogenic
      gene expressions of BMMSCs in various scaffolds were determined with reverse
      transcription polymerase chain reaction (RT-PCR). Growth factor releasing profile
      and mechanical tests were performed. CCK-8 assay confirmed greater cell retention
      and proliferation in chitosan and hybrid groups. Confocal microscopy showed even
      distribution of cells in the hybrid system. After 2-week osteogenic culture in
      vitro, BMMSCs in hybrid and chitosan scaffolds showed stronger osteogenesis and
      bone-matrix formation. To conclude, chitosan/PCL hybrid scaffolds are a favorable
      platform for BTE due to its capacity to carry cells and drugs, and excellent
      mechanical strength.

PMID- 29042615
TI  - Roles of bulk and surface magnetic anisotropy on the longitudinal spin Seebeck
      effect of Pt/YIG.
AB  - A clear understanding of the temperature evolution of the longitudinal spin
      Seebeck effect (LSSE) in the classic Pt/yttrium iron garnet (YIG) system and its
      association with magnetic anisotropy is essential towards optimization of its
      spin-caloric functionality for spintronics applications. We report here for the
      first time the temperature dependences of LSSE voltage (V LSSE),
      magnetocrystalline anisotropy field (H K) and surface perpendicular magnetic
      anisotropy field (H KS) in the same Pt/YIG system. We show that on lowering
      temperature, the sharp drop in V LSSE and the sudden increases in H K and H KS at
      ~175 K are associated with the spin reorientation due to single ion anisotropy of
      Fe2+ ions. The V LSSE peak at ~75 K is attributed to the H KS and M S (saturation
      magnetization) whose peaks also occur at the same temperature. The effects of
      surface and bulk magnetic anisotropies are corroborated with those of thermally
      excited magnon number and magnon propagation length to satisfactorily explain the
      temperature dependence of LSSE in the Pt/YIG system. Our study also emphasizes
      the important roles of bulk and surface anisotropies in the LSSE in YIG and paves
      a new pathway for developing novel spin-caloric materials.

PMID- 29042616
TI  - Reduced nitric oxide levels during drought stress promote drought tolerance in
      barley and is associated with elevated polyamine biosynthesis.
AB  - Nitric oxide (NO) is a key messenger in plant stress responses but its exact role
      in drought response remains unclear. To investigate the role of NO in drought
      response we employed transgenic barley plants (UHb) overexpressing the barley non
      symbiotic hemoglobin gene HvHb1 that oxidizes NO to NO3-. Reduced NO production
      under drought conditions in UHb plants was associated with increased drought
      tolerance. Since NO biosynthesis has been related to polyamine metabolism, we
      investigated whether the observed drought-related NO changes could involve
      polyamine pathway. UHb plants showed increases in total polyamines and in
      particular polyamines such as spermidine. These increases correlated with the
      accumulation of the amino acid precursors of polyamines and with the expression
      of specific polyamine biosynthesis genes. This suggests a potential interplay
      between NO and polyamine biosynthesis during drought response. Since ethylene has
      been linked to NO signaling and it is also related to polyamine metabolism, we
      explored this connection. In vivo ethylene measurement showed that UHb plants
      significantly decrease ethylene production and expression of aminocyclopropane-1
      carboxylic acid synthase gene, the first committed step in ethylene biosynthesis
      compared with wild type. These data suggest a NO-ethylene influenced regulatory
      node in polyamine biosynthesis linked to drought tolerance/susceptibility in
      barley.

PMID- 29042618
TI  - Investigating the relationship between Aerosol Optical Depth and Precipitation
      over Southeast Asia with Relative Humidity as an influencing factor.
AB  - Atmospheric aerosols influence precipitation by changing the earth's energy
      budget and cloud properties. A number of studies have reported correlations
      between aerosol properties and precipitation data. Despite previous research, it
      is still hard to quantify the overall effects that aerosols have on precipitation
      as multiple influencing factors such as relative humidity (RH) can distort the
      observed relationship between aerosols and precipitation. Thus, in this study,
      both satellite-retrieved and reanalysis data were used to investigate the
      relationship between aerosols and precipitation in the Southeast Asia region from
      2001 to 2015, with RH considered as a possible influencing factor. Different
      analyses in the study indicate that a positive correlation was present between
      Aerosol Optical Depth (AOD) and precipitation over northern Southeast Asia region
      during the autumn and the winter seasons, while a negative correlation was
      identified over the Maritime Continent during the autumn season. Subsequently, a
      partial correlation analysis revealed that while RH influences the long-term
      negative correlations between AOD and precipitation, it did not significantly
      affect the positive correlations seen in the winter season. The result of this
      study provides additional evidence with respect to the critical role of RH as an
      influencing factor in AOD-precipitation relationship over Southeast Asia.

PMID- 29042617
TI  - Expression and function of Abcg4 in the mouse blood-brain barrier: role in
      restricting the brain entry of amyloid-beta peptide.
AB  - ABCG4 is an ATP-binding cassette transmembrane protein which has been shown, in
      vitro, to participate in the cellular efflux of desmosterol and amyloid-beta
      peptide (Abeta). ABCG4 is highly expressed in the brain, but its localization and
      function at the blood-brain barrier (BBB) level remain unknown. We demonstrate by
      qRT-PCR and confocal imaging that mouse Abcg4 is expressed in the brain capillary
      endothelial cells. Modelling studies of the Abcg4 dimer suggested that
      desmosterol showed thermodynamically favorable binding at the putative sterol
      binding site, and this was greater than for cholesterol. Additionally, unbiased
      docking also showed Abeta binding at this site. Using a novel Abcg4-deficient
      mouse model, we show that Abcg4 was able to export Abeta and desmosterol at the
      BBB level and these processes could be inhibited by probucol and L-thyroxine. Our
      assay also showed that desmosterol antagonized the export of Abeta, presumably as
      both bind at the sterol-binding site on Abcg4. We show for the first time that
      Abcg4 may function in vivo to export Abeta at the BBB, in a process that can be
      antagonized by its putative natural ligand, desmosterol (and possibly
      cholesterol).

PMID- 29042619
TI  - Diffusion tensor image features predict IDH genotype in newly diagnosed WHO grade
      II/III gliomas.
AB  - We hypothesized that machine learning analysis based on texture information from
      the preoperative MRI can predict IDH mutational status in newly diagnosed WHO
      grade II and III gliomas. This retrospective study included in total 79
      consecutive patients with a newly diagnosed WHO grade II or III glioma. Local
      binary pattern texture features were generated from preoperative B0 and
      fractional anisotropy (FA) diffusion tensor imaging. Using a training set of 59
      patients, a single hidden layer neural network was then trained on the texture
      features to predict IDH status. The model was validated based on the prediction
      accuracy calculated in a previously unseen set of 20 gliomas. Prediction accuracy
      of the generated model was 92% (54/59 cases; AUC = 0.921) in the training and 95%
      (19/20; AUC = 0.952) in the validation cohort. The ten most important features
      were comprised of tumor size and both B0 and FA texture information, underlining
      the joint contribution of imaging data to classification. Machine learning
      analysis of DTI texture information and tumor size reliably predicts IDH status
      in preoperative MRI of gliomas. Such information may increasingly support
      individualized surgical strategies, supplement pathological analysis and
      highlight the potential of radiogenomics.

PMID- 29042620
TI  - An Integrin-Targeted, Highly Diffusive Construct for Photodynamic Therapy.
AB  - Targeted antineoplastic agents show great promise in the treatment of cancer,
      having the ability to impart cytotoxicity only to specific tumor types. However,
      these therapies do not experience uniform uptake throughout tumors, leading to
      sub-lethal cell killing that can impart treatment resistance, and cause
      problematic off-target effects. Here we demonstrate a photodynamic therapy
      construct that integrates both a cyclic RGD moiety for integrin-targeting, as
      well as a 5 kDa PEG chain that passivates the construct and enables its rapid
      diffusion throughout tumors. PEGylation of the photosensitizer construct was
      found to prevent photosensitizer aggregation, boost the generation of cytotoxic
      reactive radical species, and enable the rapid uptake of the construct into cells
      throughout large (>500 um diameter) 3D tumor spheroids. Replacing the cyclic RGD
      with the generic RAD peptide led to the loss of cellular uptake in 3D culture,
      demonstrating the specificity of the construct. Photodynamic therapy with the
      construct was successful in inducing cytotoxicity, which could be competitively
      blocked by a tenfold concentration of free cyclic RGD. This construct is a first
      of-its kind theranostic that may serve as a new approach in our growing
      therapeutic toolbox.

PMID- 29042621
TI  - Postnatal Development of the Murine Notochord Remnants Quantified by High
      resolution Contrast-enhanced MicroCT.
AB  - The notochord gives rise to spinal segments during development, and it becomes
      embedded within the nucleus pulposus of the intervertebral disc (IVD) during
      maturation. The disruption of the notochord band has been observed with IVD
      degeneration. Since the mechanical competence of the IVD relies on its structural
      constituents, defining the structure of the notochord during aging is critical
      for investigations relating to IVD function and homeostasis. The assessment and
      imaging of the notochord has classically relied on histological techniques, which
      introduces sectioning artifacts during preparation and spatial biases. Magnetic
      resonance imaging (MRI) does not offer sufficient resolution to discriminate the
      notochord from the surrounding the nucleus pulposus, especially in murine models.
      Current X-ray based computed tomography systems provide imaging resolutions down
      to the single- and sub- micron scales, and when coupled with contrast-enhancing
      agents, enable the high-resolution three-dimensional imaging of relatively small
      features. Utilizing phosphomolybdic acid to preferentially bind to collagen
      cationic domains, we describe the structure of the notochord remnants with aging
      in the lumbar IVDs of BALB/c mice. These results provide a highly quantitative
      and sensitive approach to monitoring the IVD during postnatal development.

PMID- 29042622
TI  - Surface Decoration of Pt Nanoparticles via ALD with TiO2 Protective Layer on
      Polymeric Nanofibers as Flexible and Reusable Heterogeneous Nanocatalysts.
AB  - Coupling the functional nanoheterostructures over the flexible polymeric
      nanofibrous membranes through electrospinning followed by the atomic layer
      deposition (ALD), here we presented a high surface area platform as flexible and
      reusable heterogeneous nanocatalysts. Here, we show the ALD of titanium dioxide
      (TiO2) protective nanolayer onto the electrospun polyacrylonitrile (PAN)
      nanofibrous web and then platinum nanoparticles (Pt-NP) decoration was performed
      by ALD onto TiO2 coated PAN nanofibers. The free-standing and flexible Pt-NP/TiO2
      PAN nanofibrous web showed the enhancive reduction of 4-nitrophenol (4-NP) to 4
      aminophenol (4-AP) within 45 seconds though the hydrogenation process with the
      degradation rate of 0.1102 s-1. The TiO2 protective layer on the PAN polymeric
      nanofibers was presented as an effective route to enhance the attachment of Pt-NP
      and to improve the structure stability of polymeric nanofibrous substrate.
      Commendable enhancement in the catalytic activity with the catalytic dosage and
      the durability after the reusing cycles were investigated over the reduction of 4
      NP. Even after multiple usage, the Pt-NP/TiO2-PAN nanofibrous webs were stable
      with the flexible nature with the presence of Pt and TiO2 on its surface.

PMID- 29042623
TI  - The protein phosphatase 1 regulator NIPP1 is essential for mammalian
      spermatogenesis.
AB  - NIPP1 is one of the major nuclear interactors of protein phosphatase PP1. The
      deletion of NIPP1 in mice is early embryonic lethal, which has precluded
      functional studies in adult tissues. Hence, we have generated an inducible NIPP1
      knockout model using a tamoxifen-inducible Cre recombinase transgene. The
      inactivation of the NIPP1 encoding alleles (Ppp1r8) in adult mice occurred very
      efficiently in testis and resulted in a gradual loss of germ cells, culminating
      in a Sertoli-cell only phenotype. Before the overt development of this phenotype
      Ppp1r8 -/- testis showed a decreased proliferation and survival capacity of cells
      of the spermatogenic lineage. A reduced proliferation was also detected after the
      tamoxifen-induced removal of NIPP1 from cultured testis slices and isolated germ
      cells enriched for undifferentiated spermatogonia, hinting at a testis-intrinsic
      defect. Consistent with the observed phenotype, RNA sequencing identified changes
      in the transcript levels of cell-cycle and apoptosis regulating genes in NIPP1
      depleted testis. We conclude that NIPP1 is essential for mammalian
      spermatogenesis because it is indispensable for the proliferation and survival of
      progenitor germ cells, including (un)differentiated spermatogonia.

PMID- 29042625
TI  - Radiation Resistance of Silicon Carbide Schottky Diode Detectors in D-T Fusion
      Neutron Detection.
AB  - Silicon carbide (SiC) is a wide band-gap semiconductor material with many
      excellent properties, showing great potential in fusion neutron detection. The
      radiation resistance of 4H-SiC Schottky diode detectors was studied
      experimentally by carefully analyzing the detectors' properties before and after
      deuterium-tritium fusion neutron irradiation with the total fluence of 1.31 *
      1014 n/cm2 and 7.29 * 1014 n/cm2 at room temperature. Significant degradation has
      been observed after neutron irradiation: reverse current increased greatly, over
      three to thirty fold; Schottky junction was broken down; significant lattice
      damage was observed at low temperature photoluminescence measurements; the peaks
      of alpha particle response spectra shifted to lower channels and became wider;
      the charge collection efficiency (CCE) decreased by about 7.0% and 22.5% at 300 V
      with neutron irradiation fluence of 1.31 * 1014 n/cm2 and 7.29 * 1014 n/cm2,
      respectively. Although the degradation exists, the SiC detectors successfully
      survive intense neutron radiation and show better radiation resistance than
      silicon detectors.

PMID- 29042624
TI  - Worsening calcification propensity precedes all-cause and cardiovascular
      mortality in haemodialyzed patients.
AB  - A novel in-vitro test (T50-test) assesses ex-vivo serum calcification propensity
      which predicts mortality in HD patients. The association of longitudinal changes
      of T50 with all-cause and cardiovascular mortality has not been investigated. We
      assessed T50 in paired sera collected at baseline and at 24 months in 188
      prevalent European HD patients from the ISAR cohort, most of whom were
      Caucasians. Patients were followed for another 19 [interquartile range: 11-37]
      months. Serum T50 exhibited a significant decline between baseline and 24 months
      (246 +/- 64 to 190 +/- 68 minutes; p < 0.001). With serum Delta-phosphate showing
      the strongest independent association with declining T50 (r = -0.39; p < 0.001)
      in multivariable linear regression. The rate of decline of T50 over 24 months was
      a significant predictor of all-cause (HR = 1.51 per 1SD decline, 95% CI: 1.04 to
      2.2; p = 0.03) and cardiovascular mortality (HR = 2.15; 95% CI: 1.15 to 3.97; p =
      0.02) in Kaplan Meier and multivariable Cox-regression analysis, while cross
      sectional T50 at inclusion and 24 months were not. Worsening serum calcification
      propensity was an independent predictor of mortality in this small cohort of
      prevalent HD patients. Prospective larger scaled studies are needed to assess the
      value of calcification propensity as a longitudinal parameter for risk
      stratification and monitoring of therapeutic interventions.

PMID- 29042626
TI  - Long-term Cyclability of Substoichiometric Silicon Nitride Thin Film Anodes for
      Li-ion Batteries.
AB  - Silicon has been the subject of an extensive research effort aimed at developing
      new anode materials for lithium ion batteries due to its large specific and
      volumetric capacity. However, commercial use is limited by a number of
      degradation problems, many of which are related to the large volume change the
      material undergoes during cycling in combination with limited lithium
      diffusivity. Silicon rich silicon oxides (SiOx), which converts into active
      silicon and inactive lithium oxide during the initial lithiation, have attracted
      some attention as a possible solution to these issues. In this work we present an
      investigation of silicon rich amorphous silicon nitride (a-SiNx) as an
      alternative convertible anode material. Amorphous SiN0.89 thin films deposited by
      plasma enhanced chemical vapour deposition show reversible reactions with lithium
      when cycled between 0.05 and 1.0 V vs. Li+/Li. This material delivers a
      reversible capacity of approximately 1,200 mAh/g and exhibits excellent cycling
      stability, with 41 nm a-SiN0.89 thin film electrodes showing negligible capacity
      degradation over more than 2,400 cycles.

PMID- 29042627
TI  - TIPE2 negatively regulates mycoplasma pneumonia-triggered immune response via
      MAPK signaling pathway.
AB  - Excessive immune responses played an important role in pathophysiology of
      mycoplasma pneumonia (MP) infection. Tumor necrosis factor-alpha-induced protein
      8-like 2 (TIPE2) is a negative regulator of immune response. This study
      investigated the expression change of TIPE2 and its role in immune defense
      against MP infection, as well as the underlying mechanisms. Expressions of TIPE2
      both in patients and in macrophages in vitro after MP infection were measured. We
      further studied cytokine production and mitogen-activated protein kinase (MAPK)
      signaling function in macrophages with interfered expression of TIPE2 upon MP
      infection. A significant decrease of TIPE2 mRNA expression was observed in
      peripheral blood mononuclear cells (PBMCs) from MP patients, which was correlated
      with the severity of infection. Accordingly we found down-regulation of TIPE2
      expression in macrophages after MP infection. In vitro study further suggested
      that TIPE2 jeopardized inflammatory cytokine production trigged by MP infection
      via inhibiting MAPK signaling pathway. These findings provided evidences of the
      novel function of TIPE2 in anti-MP immunity and its possible clinical utility
      related clinical significance.

PMID- 29042628
TI  - A DNA Contact Map for the Mouse Runx1 Gene Identifies Novel Haematopoietic
      Enhancers.
AB  - The transcription factor Runx1 is essential for definitive haematopoiesis, and
      the RUNX1 gene is frequently translocated or mutated in leukaemia. Runx1 is
      transcribed from two promoters, P1 and P2, to give rise to different protein
      isoforms. Although the expression of Runx1 must be tightly regulated for normal
      blood development, the mechanisms that regulate Runx1 isoform expression during
      haematopoiesis remain poorly understood. Gene regulatory elements located in non
      coding DNA are likely to be important for Runx1 transcription. Here we use
      circular chromosome conformation capture sequencing to identify DNA interactions
      with the P1 and P2 promoters of Runx1, and the previously identified +24
      enhancer, in the mouse multipotent haematopoietic progenitor cell line HPC-7. The
      active promoter, P1, interacts with nine non-coding regions that are occupied by
      transcription factors within a 1 Mb topologically associated domain. Eight of
      nine regions function as blood-specific enhancers in zebrafish, of which two were
      previously shown to harbour blood-specific enhancer activity in mice.
      Interestingly, the +24 enhancer interacted with multiple distant regions on
      chromosome 16, suggesting it may regulate the expression of additional genes. The
      Runx1 DNA contact map identifies connections with multiple novel and known
      haematopoietic enhancers that are likely to be involved in regulating Runx1
      expression in haematopoietic progenitor cells.

PMID- 29042629
TI  - Development of a real-time fluorescence loop-mediated isothermal amplification
      assay for rapid and quantitative detection of Ustilago maydis.
AB  - The common smut of corn, caused by Ustilago maydis is a troublesome disease of
      maize. Early and accurate detection of U. maydis is essential for the disease
      management. In this study, primer set Pep-2 was selected for LAMP (loop-mediated
      isothermal amplification) from 12 sets of primers targeting three U. maydis
      effector genes See1, Pit2 and Pep1 according to primer screening. The optimal
      concentrations of Bst DNA polymerase and Mg2+ as well as inner/outer primer ratio
      of the LAMP reaction system were screened by combining a single factor experiment
      and an orthogonal design arrangement. The specificity of this real-time LAMP
      (RealAmp) assay was confirmed by negative testing for other pathogens. The
      detection sensitivity of the RealAmp assay was 200 times higher than that of
      detection through conventional PCR. Results of the RealAmp assay for quantifying
      the genomic DNA of U. maydis were confirmed by testing with both artificially and
      naturally infected samples. In addition, the RealAmp reaction could be conducted
      via an improved tube scanner to implement a "electricity free" assay from
      template preparation to quantitative detection. The resulting assay could be more
      convenient for use in the field as a simple, rapid, and effective technique for
      monitoring U. maydis.

PMID- 29042630
TI  - Controlling sound radiation through an opening with secondary loudspeakers along
      its boundaries.
AB  - We propose a virtual sound barrier system that blocks sound transmission through
      openings without affecting access, light and air circulation. The proposed system
      applies active control technique to cancel sound transmission with a double
      layered loudspeaker array at the edge of the opening. Unlike traditional
      transparent glass windows, recently invented double-glazed ventilation windows
      and planar active sound barriers or any other metamaterials designed to reduce
      sound transmission, secondary loudspeakers are put only along the boundaries of
      the opening, which provides the possibility to make it invisible. Simulation and
      experimental results demonstrate its feasibility for broadband sound control,
      especially for low frequency sound which is usually hard to attenuate with
      existing methods.

PMID- 29042631
TI  - Prognostic significance of preoperative gamma-glutamyltransferase to lymphocyte
      ratio index in nonfunctional pancreatic neuroendocrine tumors after curative
      resection.
AB  - Various inflammation-based prognostic scores have been associated with reduced
      survival in patients with nonfunctional pancreatic neuroendocrine tumor (NF
      PNET). However, few studies have illuminated the relationship between the
      preoperative gamma-glutamyltransferase (GGT) to lymphocyte ratio index (GLRI) and
      the prognosis of NF-PNET. A retrospective review of 125 NF-PNET patients
      following curative resection was conducted. The cut-off values for the
      inflammation-based prognostic scores, including GLRI, were selected using
      receiver operating characteristic curve analysis. Univariate, multivariate and
      Kaplan-Meier analyses were used to calculate overall survival (OS) and disease
      free survival (DFS). The optimal cut-off value for GLRI was 10.3. Multivariate
      analysis showed that GLRI was an independent predictor of OS (P = 0.001) and DFS
      (P = 0.007) for NF-PNET. Kaplan-Meier analysis also showed that preoperative GLRI
      had significant prognostic value in various subgroups of patients with NF-PNET.
      The discriminatory capability of GLRI was superior to that of other inflammation
      based scores in OS prediction. Furthermore, the predictive range was expanded by
      incorporating GLRI into the conventional stratification systems, including AJCC
      staging and WHO classification. These results indicated that preoperative GLRI
      was an independent predictor for NF-PNET patients undergoing curative resection.
      The incorporation of GLRI into the existing conventional stratification systems
      resulted in improved predictive accuracy.

PMID- 29042632
TI  - The potential for coral reef establishment through free-living stabilization.
AB  - Corals thrive in a variety of environments, from low wave and tidal energy
      lagoons, to high energy tidal reef flats, but remain dependent upon suitable
      substrate. Herein we reviewed the phenomenon of free-living corals (coralliths),
      examined whether they have the capacity to create their own stable habitat in
      otherwise uninhabitable, poor substrate environments through 'free-living
      stabilization', and explore their potential ecological role on coral reefs. This
      stabilization could be achieved by coral settlement and survival on mobile
      substrate, with subsequent growth into free-living coralliths until a critical
      mass is reached that prevents further movement. This allows for secondary reef
      colonization by other coral species. To preliminarily test this hypothesis we
      provide evidence that the potential to support secondary coral colonisation
      increases with corallith size. Due to the limited diversity of corallith species
      observed here and in the literature, and the lack of physiological differences
      exhibited by coralliths here to static controls, it seems likely that only a
      small selection of coral species have the ability to form coralliths, and the
      potential to create their own stable habitat.

PMID- 29042633
TI  - Catsper1 promoter is bidirectional and regulates the expression of a novel
      lncRNA.
AB  - The Catsper1 gene, whose expression is restricted to male germ cells, has great
      importance in reproductive biology because of its function in sperm motility and
      fertilization. We previously reported that the promoter of this gene has
      transcriptional activity in either direction in a heterologous system. In the
      present study, we found that the Catsper1 promoter has in vitro transcriptional
      activity in either orientation in GC-1 spg mouse spermatogonial cells. The
      results also showed that this promoter regulates the expression of a new
      divergent Catsper1 gene named Catsper1au (Catsper1 antisense upstream
      transcript). Catsper1au is expressed in adult male mouse testis and liver tissues
      but not in female mouse liver or ovary tissues. In the testis, Catsper1au is
      expressed in embryos at 11.5 days post-coitum and from newborns to adults. This
      gene is also expressed in 1- to 3-week postnatal hearts and in 1-week to adult
      stage livers. The analysis of the 1402 bp whole genome sequence revealed that
      Catsper1au is an intronless and polyadenylated lncRNA, located in the nuclei of
      Sertoli and spermatogenic cells from adult testis. These data indicate that
      Catsper1au is divergently expressed from the Catsper1 promoter and could regulate
      gene expression during spermatogenesis.

PMID- 29042634
TI  - A novel quantification-driven proteomic strategy identifies an endogenous peptide
      of pleiotrophin as a new biomarker of Alzheimer's disease.
AB  - We present a new, quantification-driven proteomic approach to identifying
      biomarkers. In contrast to the identification-driven approach, limited in scope
      to peptides that are identified by database searching in the first step, all MS
      data are considered to select biomarker candidates. The endopeptidome of
      cerebrospinal fluid from 40 Alzheimer's disease (AD) patients, 40 subjects with
      mild cognitive impairment, and 40 controls with subjective cognitive decline was
      analyzed using multiplex isobaric labeling. Spectral clustering was used to match
      MS/MS spectra. The top biomarker candidate cluster (215% higher in AD compared to
      controls, area under ROC curve = 0.96) was identified as a fragment of
      pleiotrophin located near the protein's C-terminus. Analysis of another cohort (n
      = 60 over four clinical groups) verified that the biomarker was increased in AD
      patients while no change in controls, Parkinson's disease or progressive
      supranuclear palsy was observed. The identification of the novel biomarker
      pleiotrophin 151-166 demonstrates that our quantification-driven proteomic
      approach is a promising method for biomarker discovery, which may be universally
      applicable in clinical proteomics.

PMID- 29042635
TI  - Remarkably enhanced current-driven 360 degrees  domain wall motion in nanostripe
      by tuning in-plane biaxial anisotropy.
AB  - By micromagnetic simulations, we study the current-driven 360 degrees  domain
      wall (360DW) motion in ferromagnetic nanostripe with an in-plane biaxial
      anisotropy. We observe the critical annihilation current of 360 degrees  domain
      wall can be enhanced through such a type of anisotropy, the reason of which is
      the suppression of out-of-plane magnetic moments generated simultaneously with
      domain-wall motion. In details, We have found that the domain-wall width is only
      related to K y  - K x , with K x(y) the anisotropy constant in x(y) direction.
      Taking domain-wall width into consideration, a prior choice is to keep K y  ~ K x
      with large enough K. The mode of domain-wall motion has been investigated as
      well. The traveling-wave-motion region increases with K, while the average DW
      velocity is almost unchanged. Another noteworthy feature is that a Walker
      breakdown-like motion exists before annihilation. In this region, though domain
      wall moves with an oscillating behavior, the average velocity does not reduce
      dramatically, but even rise again for a large K.

PMID- 29042636
TI  - Dysfunctional Early Processing of Facial Expressions in Hazardous Drinkers:
      Evidence from an ERP Study.
AB  - Chronic alcohol intoxication impairs multiple cognitive functions. According to
      the dual system model (DSM), the development of alcohol dependence (AD) involves
      the imbalance between the automatic-affective system and the reflective system.
      However, the cognitive functions of non-AD hazardous drinkers (HDs) remain
      unclear. The present study aimed to explore how the HDs process facial
      expressions differently from the healthy subjects. Sixteen HDs and seventeen
      control subjects (CSs) completed an emotional working memory (WM) task while the
      electroencephalogram (EEG) was recorded. We found that there was no significant
      group difference in behavioral performance between the two groups. In the ERP
      data, relative to the CSs, the HDs showed delayed latencies of P1 and N170.
      Moreover, the CSs showed significant differences between the amplitudes of
      neural/fear and disgust expressions while these differences were insignificant in
      the HDs. The current results suggest that the main deficits in the processing of
      facial expression in HDs existed in the early automatic-affective system instead
      of in the reflective system.

PMID- 29042637
TI  - The polyglutamine protein ataxin-3 enables normal growth under heat shock
      conditions in the methylotrophic yeast Pichia pastoris.
AB  - The protein ataxin-3 carries a polyglutamine stretch close to the C-terminus that
      triggers a neurodegenerative disease in humans when its length exceeds a critical
      threshold. A role as a transcriptional regulator but also as a ubiquitin
      hydrolase has been proposed for this protein. Here, we report that, when
      expressed in the yeast Pichia pastoris, full-length ataxin-3 enabled almost
      normal growth at 37  degrees C, well above the physiological optimum of 30 
      degrees C. The N-terminal Josephin domain (JD) was also effective but
      significantly less, whereas catalytically inactive JD was completely ineffective.
      Based on MudPIT proteomic analysis, we observed that the strain expressing full
      length, functional ataxin-3 displayed persistent upregulation of enzymes involved
      in mitochondrial energy metabolism during growth at 37  degrees C compared with
      the strain transformed with the empty vector. Concurrently, in the transformed
      strain intracellular ATP levels at 37  degrees C were even higher than normal
      ones at 30  degrees C. Elevated ATP was also paralleled by upregulation of
      enzymes involved in both protein biosynthesis and biosynthetic pathways, as well
      as of several stress-induced proteins. A similar pattern was observed when
      comparing a strain expressing JD with another expressing its catalytically
      inactive counterpart. We suggest that such effects mostly result from mechanisms
      of transcriptional regulation.

PMID- 29042638
TI  - Carbon nanowalls as a platform for biological SERS studies.
AB  - Herein we report about developing new type of Surface Enhanced Raman Scattering
      (SERS) substrates based on Au-decorated carbon nanowalls. The designed substrates
      possess high specific surface area and high sensitivity. Chemical stability of Au
      perfectly blends with electrical properties and high value of specific surface
      area of carbon nanowalls. Created structures were applied to detect signals of a
      typical molecule used for SERS substrates testing, rhodamine 6G, which exhibits
      electronic absorption in the visible area of spectrum, and biomacromolecules such
      as tryptophan, guanine, bovine serum albumin and keratin hydrolysates, whose
      electronic absorption is in the ultraviolet region of spectrum and lies far from
      the Au plasmonic resonance. The obtained signals for these compounds suggest that
      the developed substrate is a prominent platform for the detection of biological
      macromolecules. The properties of the substrate, including its morphology and Au
      film thickness, as well as the analyte deposition method, were optimized to
      achieve the optimum Raman signal enhancement. Electric field distribution in the
      designed structures was calculated to describe the observed dependence of SERS
      activity on the substrate morphology.

PMID- 29042639
TI  - School-based assessment of amblyopia and strabismus among multiethnic children in
      rural China.
AB  - We aimed to determine the prevalence and possible ethnic variations in strabismus
      and amblyopia among multiethnic school-aged children in rural China. A total of
      9,263 children (4,347 Han, 3,352 Yi, 799 Dai and 765 Bai) aged 6 to 14 years were
      analyzed. Comprehensive eye examinations including monocular distance visual
      acuity, anterior segment examination, autorefraction, cover testing and ocular
      motility were conducted. Manifested strabismus was detected in 3.53% of the
      overall population. The prevalence of strabismus was 3.29% in Han, 4.12% in Yi,
      2.25% in Dai, and 3.66% in Bai ethnic groups with marginally inter-ethnic
      differences (P = 0.046). There was an increasing trend in the prevalence of
      strabismus with increasing age (P < 0.001). Amblyopia affected 132 children
      (1.43%) overall, with no statistical differences in gender and age. The
      prevalence of amblyopia was highest in Dai ethnic group (2.00%) and lowest in
      ethnic Yi ethnic group (1.04%) with no significant difference being detected (P =
      0.062). Refractive error and strabismus were the two major factors associated
      with amblyopia. No significant ethnic differences in strabismus and amblyopia
      among Chinese ethnic minorities were observed. Refractive error and strabismus
      were the major causes for amblyopia in rural Chinese children.

PMID- 29042641
TI  - Unconscious avoidance of eye contact in autism spectrum disorder.
AB  - Atypical responses to direct gaze are one of the most characteristic hallmarks of
      autism spectrum disorder (ASD). The cause and mechanism underlying this
      phenomenon, however, have remained unknown. Here we investigated whether the
      atypical responses to eye gaze in autism spectrum disorder is dependent on the
      conscious perception of others' faces. Face stimuli with direct and averted gaze
      were rendered invisible by interocular suppression and eye movements were
      recorded from participants with ASD and an age and sex matched control group.
      Despite complete unawareness of the stimuli, the two groups differed
      significantly in their eye movements to the face stimuli. In contrast to the
      significant positive saccadic index observed in the TD group, indicating an
      unconscious preference to the face with direct gaze, the ASD group had no such
      preference towards direct gaze and instead showed a tendency to prefer the face
      with averted gaze, suggesting an unconscious avoidance of eye contact. These
      results provide the first evidence that the atypical response to eye contact in
      ASD is an unconscious and involuntary response. They provide a better
      understanding of the mechanism of gaze avoidance in autism and might lead to new
      diagnostic and therapeutic interventions.

PMID- 29042640
TI  - Validation of multiplex immunofluorescence panels using multispectral microscopy
      for immune-profiling of formalin-fixed and paraffin-embedded human tumor tissues.
AB  - Immune-profiling is becoming an important tool to identify predictive markers for
      the response to immunotherapy. Our goal was to validate multiplex
      immunofluorescence (mIF) panels to apply to formalin-fixed and paraffin-embedded
      tissues using a set of immune marker antibodies, with the OpalTM 7 color Kit
      (PerkinElmer) in the same tissue section. We validated and we described two
      panels aiming to characterize the expression of PD-L1, PD-1, and subsets of tumor
      associated immune cells. Panel 1 included pancytokeratin (AE1/AE3), PD-L1, CD4,
      CD8, CD3, CD68, and DAPI, and Panel 2 included pancytokeratin, PD-1, CD45RO,
      granzyme B, CD57, FOXP3, and DAPI. After all primary antibodies were tested in
      positive and negative controls by immunohistochemistry and uniplex IF, panels
      were developed and simultaneous marker expressions were quantified using the
      Vectra 3.0TM multispectral microscopy and image analysis InFormTM 2.2.1 software
      (PerkinElmer).These two mIF panels demonstrated specific co-localization in
      different cells that can identify the expression of PD-L1 in malignant cells and
      macrophages, and different T-cell subpopulations. This mIF methodology can be an
      invaluable tool for tumor tissue immune-profiling to allow multiple targets in
      the same tissue section and we provide that is accurate and reproducible method
      when is performed carefully under pathologist supervision.

PMID- 29042642
TI  - Modeling the climatic suitability of leishmaniasis vector species in Europe.
AB  - Climate change will affect the geographical distribution of many species in the
      future. Phlebotomine sandflies are vector species for leishmaniasis, a tropical
      neglected disease. We applied an ensemble forecasting niche modeling approach to
      project future changes in climatic suitability for ten vector competent sandfly
      species in Europe. Whereas the main area of sandfly distribution currently lies
      in the Mediterranean region, models generally projected a northwards expansion of
      areas with suitable climatic conditions for most species (P. alexandri, P.
      neglectus, P. papatasi, P. perfiliewi, P. tobbi) in the future. The range of
      distribution for only two species (P. ariasi, P. mascittii) was projected to
      decline in the future. According to our results, a higher number of vector
      competent species in Central Europe can generally be expected, assuming no
      limitations to dispersal. We recommend monitoring for the establishment of vector
      species, especially in areas with projected climatic suitability for multiple
      vector species, as a precautious strategy. An increased number of vector species,
      or a higher abundance of a single species, might result in a higher transmission
      risk of leishmaniasis, provided that the pathogens follow the projected range
      shifts.

PMID- 29042643
TI  - Measuring the Poisson's Ratio of Fibronectin Using Engineered Nanofibers.
AB  - The extracellular matrix (ECM) is a fibrillar protein-based network, the physical
      and chemical properties of which can influence a multitude of cellular processes.
      Despite having an important role in cell and tissue signaling, a complete chemo
      mechanical characterization of ECM proteins such as fibronectin (FN) is lacking.
      In this study, we engineered monodisperse FN nanofibers using a surface-initiated
      assembly technique in order to provide new insight into the elastic behavior of
      this material over large deformations. FN nanofibers were patterned on surfaces
      in a pre-stressed state and when released from the surface underwent rapid
      contraction. We found that the FN nanofibers underwent 3.3-fold and 9-fold
      changes in length and width, respectively, and that the nanofiber volume was
      conserved. Volume was also conserved following uniaxial extension of the FN
      nanofibers of ~2-fold relative to the patterned state. This data suggests that
      the FN networks we engineered formed an incompressible material with a Poisson's
      ratio of ~0.5. While the Poisson's ratio of cells and other biological materials
      are widely estimated as 0.5, our experimental results demonstrate that for FN
      networks this is a reasonable approximation.

PMID- 29042644
TI  - HIV-1 viral protein R (Vpr) induces fatty liver in mice via LXRalpha and
      PPARalpha dysregulation: implications for HIV-specific pathogenesis of NAFLD.
AB  - HIV patients develop hepatic steatosis. We investigated hepatic steatosis in
      transgenic mice expressing the HIV-1 accessory protein Vpr (Vpr-Tg) in liver and
      adipose tissues, and WT mice infused with synthetic Vpr. Vpr-Tg mice developed
      increased liver triglyceride content and elevated ALT, bilirubin and alkaline
      phosphatase due to three hepatic defects: 1.6-fold accelerated de novo
      lipogenesis (DNL), 45% slower fatty acid beta-oxidation, and 40% decreased VLDL
      triglyceride export. Accelerated hepatic DNL was due to coactivation by Vpr of
      liver X receptor-alpha (LXRalpha) with increased expression of its lipogenic
      targets Srebp1c, Chrebp, Lpk, Dgat, Fasn and Scd1, and intranuclear SREBP1c and
      ChREBP. Vpr enhanced association of LXRalpha with Lxralpha and Srebp1c promoters,
      increased LXRE-LXRalpha binding, and broadly altered hepatic expression of
      LXRalpha-regulated lipid metabolic genes. Diminished hepatic fatty acid beta
      oxidation was associated with decreased mRNA expression of Pparalpha and its
      targets Cpt1, Aox, Lcad, Ehhadh, Hsd10 and Acaa2, and blunted VLDL export with
      decreased expression of Mttp and its product microsomal triglyceride transfer
      protein. With our previous findings that Vpr circulates in HIV patients
      (including those with undetectable plasma HIV-1 RNA), co-regulates the
      glucocorticoid receptor and PPARgamma and transduces hepatocytes, these data
      indicate a potential role for Vpr in HIV-associated fatty liver disease.

PMID- 29042645
TI  - Effects of intranasal insulin application on the hypothalamic BOLD response to
      glucose ingestion.
AB  - The hypothalamus is a crucial structure in the brain that responds to metabolic
      cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate
      a lack of hypothalamic neuronal response after glucose ingestion, which is
      suggested to be an underlying cause of the disease. In this study, we assessed
      whether intranasal insulin can be used to enhance neuronal hypothalamic responses
      to glucose ingestion. In a randomized, double-blinded, placebo-controlled 4
      double cross-over experiment, hypothalamic activation was measured in young non-
      diabetic subjects by determining blood-oxygen-level dependent MRI signals over 30
      minutes before and after ingestion of 75 g glucose dissolved in 300 ml water,
      under intranasal insulin or placebo condition. Glucose ingestion under placebo
      condition lead to an average 1.4% hypothalamic BOLD decrease, under insulin
      condition the average response to glucose was a 2.2% decrease. Administration of
      water did not affect the hypothalamic BOLD responses. Intranasal insulin did not
      change circulating glucose and insulin levels. Still, circulating glucose levels
      showed a significant dampening effect on the BOLD response and insulin levels a
      significant strengthening effect. Our data provide proof of concept for future
      experiments testing the potential of intranasal application of insulin to
      ameliorate defective homeostatic control in patients with type 2 diabetes.

PMID- 29042646
TI  - Effects of long-term aspirin use on molecular alterations in precancerous gastric
      mucosa in patients with and without gastric cancer.
AB  - The risk of gastric cancer (GC) remains even after H. pylori eradication; thus,
      other combination treatments, such as chemopreventive drugs, are needed. We
      evaluated the effects of aspirin on genetic/epigenetic alterations in
      precancerous conditions, i.e., atrophic mucosa (AM) and intestinal metaplasia
      (IM), in patients with chronic gastritis who had taken aspirin for more than 3
      years. A total of 221 biopsy specimens from 74 patients, including atrophic
      gastritis (AG) cases without aspirin use (control), AG cases with aspirin use (AG
      group), and GC cases with aspirin use (GC group), were analyzed. Aspirin use was
      associated with a significant reduction of CDH1 methylation in AM (OR: 0.15, 95%
      CI: 0.06-0.41, p = 0.0002), but was less effective in reversing the methylation
      that occurred in IM. Frequent hypermethylation including that of CDH1 in AM
      increased in the GC group compared to the AG group, and CDH1 methylation was an
      independent predictive marker of GC (OR: 8.50, 95% CI: 2.64-25.33, p = 0.0003).
      In patients with long-term aspirin use, the changes of molecular events in AM but
      not IM may be an important factor in the reduction of cancer incidence. In
      addition, methylation of the CDH1 gene in AM may be a surrogate of GC.

PMID- 29042647
TI  - Ultrasensitive, high-dynamic-range and broadband strain sensing by time-of-flight
      detection with femtosecond-laser frequency combs.
AB  - Ultrahigh-resolution optical strain sensors provide powerful tools in various
      scientific and engineering fields, ranging from long-baseline interferometers to
      civil and aerospace industries. Here we demonstrate an ultrahigh-resolution fibre
      strain sensing method by directly detecting the time-of-flight (TOF) change of
      the optical pulse train generated from a free-running passively mode-locked laser
      (MLL) frequency comb. We achieved a local strain resolution of 18 pepsilon/Hz1/2
      and 1.9 pepsilon/Hz1/2 at 1 Hz and 3 kHz, respectively, with large dynamic range
      of >154 dB at 3 kHz. For remote-point sensing at 1-km distance, 80 pepsilon/Hz1/2
      (at 1 Hz) and 2.2 pepsilon/Hz1/2 (at 3 kHz) resolution is demonstrated. While
      attaining both ultrahigh resolution and large dynamic range, the demonstrated
      method can be readily extended for multiple-point sensing as well by taking
      advantage of the broad optical comb spectra. These advantages may allow various
      applications of this sensor in geophysical science, structural health monitoring,
      and underwater science.

PMID- 29042648
TI  - Proteomic analysis of human lacrimal and tear fluid in dry eye disease.
AB  - To understand the pathophysiology of dry eye disease (DED), it is necessary to
      characterize proteins in the ocular surface fluids, including tear fluid (TF) and
      lacrimal fluid (LF). There have been several reports of TF proteomes, but few
      proteomic studies have examined LF secreted from the lacrimal gland (LG).
      Therefore, we characterized the proteins constituting TF and LF by liquid
      chromatography mass spectrometry. TF and LF were collected from patients with non
      Sjogren syndrome DED and from healthy subjects. Through protein profiling and
      label-free quantification, 1165 proteins from TF and 1448 from LF were
      identified. In total, 849 proteins were present in both TF and LF. Next,
      candidate biomarkers were verified using the multiple reaction monitoring assay
      in both TF and LF of 17 DED patients and 17 healthy controls. As a result, 16
      marker proteins were identified (fold-change > 1.5, p-value < 0.05), of which 3
      were upregulated in TF and 8 up- and 5 down-regulated in LF. In conclusion, this
      study revealed novel DED markers originating from the LG and tears by in-depth
      proteomic analysis and comparison of TF and LF proteins.

PMID- 29042650
TI  - Handheld Photoacoustic Microscopy Probe.
AB  - Optical resolution photoacoustic microscopy (OR-PAM) is a non-invasive, label
      free method of in vivo imaging with microscopic resolution and high optical
      contrast. Based on intrinsic contrasts, OR-PAM has expanded to include in vivo
      vessel imaging, flow cytometry, physiological parameter analysis, and single-cell
      characterization. However, since conventional OR-PAM systems have a fixed
      tabletop configuration, a large system size, and slow imaging speed, their use in
      preclinical and clinical studies remains limited. In this study, using
      microelectromechanical systems (MEMS) technology, we developed a handheld PAM
      probe with a high signal-to-noise ratio and image rate. To enable broader
      application of the OR-PAM system, we reduced its size and combined its fast
      scanning capabilities into a small handheld probe that uses a 2-axis waterproof
      MEMS scanner (2A-WP-MEMS scanner). All acoustical, optical, and mechanical
      components are integrated into a single probe with a diameter of 17 mm and a
      weight of 162 g. This study shows phantom and in vivo images of various samples
      acquired with the probe, including carbon fibers, electrospun microfibers, and
      the ear, iris, and brain of a living mouse. In particular, this study
      investigated the possibility of clinical applications for melanoma diagnosis by
      imaging the boundaries and morphology of a human mole.

PMID- 29042649
TI  - Lipid polymorphism in chloroplast thylakoid membranes - as revealed by 31P-NMR
      and time-resolved merocyanine fluorescence spectroscopy.
AB  - Chloroplast thylakoid membranes contain virtually all components of the energy
      converting photosynthetic machinery. Their energized state, driving ATP
      synthesis, is enabled by the bilayer organization of the membrane. However, their
      most abundant lipid species is a non-bilayer-forming lipid, monogalactosyl
      diacylglycerol; the role of lipid polymorphism in these membranes is poorly
      understood. Earlier 31P-NMR experiments revealed the coexistence of a bilayer and
      a non-bilayer, isotropic lipid phase in spinach thylakoids. Packing of lipid
      molecules, tested by fluorescence spectroscopy of the lipophilic dye, merocyanine
      540 (MC540), also displayed heterogeneity. Now, our 31P-NMR experiments on
      spinach thylakoids uncover the presence of a bilayer and three non-bilayer lipid
      phases; time-resolved fluorescence spectroscopy of MC540 also reveals the
      presence of multiple lipidic environments. It is also shown by 31P-NMR that: (i)
      some lipid phases are sensitive to the osmolarity and ionic strength of the
      medium, (ii) a lipid phase can be modulated by catalytic hydrogenation of fatty
      acids and (iii) a marked increase of one of the non-bilayer phases upon lowering
      the pH of the medium is observed. These data provide additional experimental
      evidence for the polymorphism of lipid phases in thylakoids and suggest that non
      bilayer phases play an active role in the structural dynamics of thylakoid
      membranes.

PMID- 29042651
TI  - Biochemistry and adaptive colouration of an exceptionally preserved juvenile
      fossil sea turtle.
AB  - The holotype (MHM-K2) of the Eocene cheloniine Tasbacka danica is arguably one of
      the best preserved juvenile fossil sea turtles on record. Notwithstanding
      compactional flattening, the specimen is virtually intact, comprising a fully
      articulated skeleton exposed in dorsal view. MHM-K2 also preserves, with great
      fidelity, soft tissue traces visible as a sharply delineated carbon film around
      the bones and marginal scutes along the edge of the carapace. Here we show that
      the extraordinary preservation of the type of T. danica goes beyond gross
      morphology to include ultrastructural details and labile molecular components of
      the once-living animal. Haemoglobin-derived compounds, eumelanic pigments and
      proteinaceous materials retaining the immunological characteristics of sauropsid
      specific beta-keratin and tropomyosin were detected in tissues containing remnant
      melanosomes and decayed keratin plates. The preserved organics represent
      condensed remains of the cornified epidermis and, likely also, deeper anatomical
      features, and provide direct chemical evidence that adaptive melanism - a
      biological means used by extant sea turtle hatchlings to elevate metabolic and
      growth rates - had evolved 54 million years ago.

PMID- 29042652
TI  - Computational Analysis of the Molecular Mechanism of RamR Mutations Contributing
      to Antimicrobial Resistance in Salmonella enterica.
AB  - Antimicrobial resistance (AMR) in pathogenic microorganisms with multidrug
      resistance (MDR) constitutes a severe threat to human health. A major causative
      mechanism of AMR is mediated through the multidrug efflux pump (MEP). The
      resistance-nodulation-division superfamily (RND family) of Gram-negative bacteria
      is usually the major cause of MDR in clinical studies. In Salmonella enterica,
      the RND pump is translated from the arcAB gene, which is regulated by the
      activator RamA. Many MEP-caused AMR strains have high ramA gene expression due to
      mutations in RamR, which has a homodimeric structure comprising the dimerization
      domain and DNA-binding domain (DBD). Three mutations on the dimerization domain,
      namely Y59H, M84I, and E160D, are far from the DBD; the molecular mechanism
      through which they influence RamR's binding affinity to the ramA gene promoter
      and consequently disrupt RamA remains unclear. The present study conducted
      molecular dynamics simulations, binding free energy calculations, and normal mode
      analysis to investigate the mechanism through which Y59H, M84I, and E160D
      mutations on the dimerization domain influence the binding affinity of RamR to
      the ramA promoter. The present results suggest that the three mutations alter the
      RamR structure, resulting in decreased DNA-binding affinity.

PMID- 29042653
TI  - Silica precipitation potentially controls earthquake recurrence in seismogenic
      zones.
AB  - Silica precipitation is assumed to play a significant role in post-earthquake
      recovery of the mechanical and hydrological properties of seismogenic zones.
      However, the relationship between the widespread quartz veins around seismogenic
      zones and earthquake recurrence is poorly understood. Here we propose a novel
      model of quartz vein formation associated with fluid advection from host rocks
      and silica precipitation in a crack, in order to quantify the timescale of crack
      sealing. When applied to sets of extensional quartz veins around the Nobeoka
      Thrust of SW Japan, an ancient seismogenic splay fault, our model indicates that
      a fluid pressure drop of 10-25 MPa facilitates the formation of typical
      extensional quartz veins over a period of 6.6 * 100-5.6 * 101 years, and that 89%
      100% of porosity is recovered within ~3 * 102 years. The former and latter
      sealing timescales correspond to the extensional stress period (~3 * 101 years)
      and the recurrence interval of megaearthquakes in the Nankai Trough (~3 * 102
      years), respectively. We therefore suggest that silica precipitation in the
      accretionary wedge controls the recurrence interval of large earthquakes in
      subduction zones.

PMID- 29042654
TI  - Electrocatalytic Performance of Chemically Synthesized PIn-Au-SGO Composite
      toward Mediated Biofuel Cell Anode.
AB  - The proposed work intended to make an intellectual contribution to the domain of
      green nanotechnology which emphasizes the chemical synthesis of a conducting
      nanocomposite based on the incorporation of gold nanoparticles (Au) into the
      redox matrix of polyindole (PIn) along with the subsequent improvement in the
      overall properties of the composite by the addition of sulfonated graphene oxide
      (SGO). The bioanode was developed by the deposition of the PIn-Au-SGO
      nanocomposite with subsequent immobilization of ferritin (Frt) and glucose
      oxidase (GOx) on the glassy carbon electrode (GC). The successful application of
      the PIn-Au-SGO nanocomposite toward the development of a ferritin-mediated
      glucose biofuel cell anode was studied by the electrochemical characterization of
      the constructed bioanode (GC-PIn-Au-SGO/Frt/GOx) for the bioelectrocatalytic
      oxidation of glucose. The maximum current density obtained by the modified
      bioanode was found to be 17.8 mA cm-2 at the limiting glucose concentration of 50
      mM in 0.1 M K4Fe(CN)6 at a scan rate of 100 mVs-1. The lifetime of the concerned
      bioelectrode when stored at 4  degrees C was estimated to be 53 days
      approximately. The appreciable results of the structural and electrochemical
      characterization of the PIn-Au-SGO based bioelectrode reveal its potential
      applications exclusively in implantable medical devices.

PMID- 29042655
TI  - Electron transfer pathways in a light, oxygen, voltage (LOV) protein devoid of
      the photoactive cysteine.
AB  - Blue-light absorption by the flavin chromophore in light, oxygen, voltage (LOV)
      photoreceptors triggers photochemical reactions that lead to the formation of a
      flavin-cysteine adduct. While it has long been assumed that adduct formation is
      essential for signaling, it was recently shown that LOV photoreceptor variants
      devoid of the photoactive cysteine can elicit a functional response and that
      flavin photoreduction to the neutral semiquinone radical is sufficient for signal
      transduction. Currently, the mechanistic basis of the underlying electron- (eT)
      and proton-transfer (pT) reactions is not well understood. We here reengineered
      pT into the naturally not photoreducible iLOV protein, a fluorescent reporter
      protein derived from the Arabidopsis thaliana phototropin-2 LOV2 domain. A single
      amino-acid substitution (Q489D) enabled efficient photoreduction, suggesting that
      an eT pathway is naturally present in the protein. By using a combination of site
      directed mutagenesis, steady-state UV/Vis, transient absorption and electron
      paramagnetic resonance spectroscopy, we investigate the underlying eT and pT
      reactions. Our study provides strong evidence that several Tyr and Trp residues,
      highly conserved in all LOV proteins, constitute the eT pathway for flavin
      photoreduction, suggesting that the propensity for photoreduction is evolutionary
      imprinted in all LOV domains, while efficient pT is needed to stabilize the
      neutral semiquinone radical.

PMID- 29042656
TI  - A new mode of contrast in biological second harmonic generation microscopy.
AB  - Enhanced image contrast in biological second harmonic imaging microscopy (SHIM)
      has previously been reported via quantitative assessments of forward- to epi
      generated signal intensity ratio and by polarization analysis. Here we
      demonstrate a new form of contrast: the material-specific, wavelength-dependence
      of epi-generated second harmonic generation (SHG) excitation efficiency, and
      discriminate collagen and myosin by ratiometric epi-generated SHG images at 920
      nm and 860 nm. Collagen shows increased SHG intensity at 920 nm, while little
      difference is detected between the two for myosin; allowing SHIM to characterize
      different SHG-generating components within a complex biological sample. We
      propose that momentum-space mapping of the second-order non-linear structure
      factor is the source of this contrast and develop a model for the forward and epi
      generated SHG wavelength-dependence. Our model demonstrates that even very small
      changes in the assumed material fibrillar structure can produce large changes in
      the wavelength-dependency of epi-generated SHG. However, in the case of forward
      SHG, although the same changes impact upon absolute intensity at a given
      wavelength, they have very little effect on wavelength-dependency beyond the
      expected monotonic fall. We also propose that this difference between forward and
      epi-generated SHG provides an explanation for many of the wavelength-dependency
      discrepancies in the published literature.

PMID- 29042657
TI  - Unravelling the Chemical Influence of Water on the PMMA/Aluminum Oxide Hybrid
      Interface In Situ.
AB  - Understanding the stability of chemical interactions at the polymer/metal oxide
      interface under humid conditions is vital to understand the long-term durability
      of hybrid systems. Therefore, the interface of ultrathin PMMA films on native
      aluminum oxide, deposited by reactive adsorption, was studied. The
      characterization of the interface of the coated substrates was performed using
      ambient pressure X-ray photoelectron spectroscopy (APXPS), Fourier transform
      infrared spectroscopy in the Kretschmann geometry (ATR-FTIR Kretschmann) and time
      of-flight secondary ion mass spectrometry (ToF-SIMS). The formation of hydrogen
      bonds and carboxylate ionic bonds at the interface are observed. The formed ionic
      bond is stable up to 5 Torr water vapour pressure as shown by APXPS. However,
      when the coated samples are exposed to an excess of aqueous electrolyte, an
      increase in the amount of carboxylate bonds at the interface, as a result of
      hydrolysis of the methoxy group, is observed by ATR-FTIR Kretschmann. These
      observations, supported by ToF-SIMS spectra, lead to the proposal of an
      adsorption mechanism of PMMA on aluminum oxide, which shows the formation of
      methanol at the interface and the effect of water molecules on the different
      interfacial interactions.

PMID- 29042658
TI  - Exosomes secreted by human adipose mesenchymal stem cells promote scarless
      cutaneous repair by regulating extracellular matrix remodelling.
AB  - Scar formation is an intractable medical problem that appears after skin wounds
      have healed. Recent research has shown that exosomes secreted by human adipose
      mesenchymal stem cells (ASC-Exos) can benefit wound healing. To further explore
      the therapeutic potential of ASC-Exos, we investigated their effects on
      mitigating scar formation, and the underlying mechanisms of these effects. We
      found that intravenous injection of ASC-Exos decreased the size of scars and
      increased the ratio of collagen III to collagen I in murine incisional wounds.
      Exosome treatment also prevented the differentiation of fibroblasts into
      myofibroblasts and increased the ratio of transforming growth factor-beta3 (TGF
      beta3) to TGF-beta1 in vivo. Additionally, we found that ASC-Exos increased the
      matrix metalloproteinases-3 (MMP3) expression of skin dermal fibroblasts by
      activating the ERK/MAPK pathway, leading to a high ratio of MMP3 to tissue
      inhibitor of matrix metalloproteinases-1 (TIMP1), which is also beneficial for
      the remodelling of extracellular matrix (ECM). In conclusion, our results
      demonstrated that ASC-Exos promote ECM reconstruction in cutaneous wound repair
      by regulating the ratios of collagen type III: type I, TGF-beta3:TGF-beta1 and
      MMP3:TIMP1, and by regulating fibroblast differentiation to mitigate scar
      formation. Therefore, the application of ASC-Exos may be a novel therapeutic
      approach for scarless wound repair.

PMID- 29042659
TI  - Giant direct and inverse magnetocaloric effect linked to the same forward
      martensitic transformation.
AB  - Metamagnetic shape memory alloys have aroused considerable attraction as
      potential magnetic refrigerants due to the large inverse magnetocaloric effect
      associated to the magnetic-field-induction of a reverse martensitic
      transformation (martensite to austenite). In some of these alloys, the austenite
      phase can be retained on cooling under high magnetic fields, being the retained
      phase metastable after field removing. Here, we report a giant direct
      magnetocaloric effect linked to the anomalous forward martensitic transformation
      (austenite to martensite) that the retained austenite undergoes on heating. Under
      moderate fields of 10 kOe, an estimated adiabatic temperature change of 9 K has
      been obtained, which is (in absolute value) almost twice that obtained in the
      conventional transformation under higher applied fields. The observation of a
      different sign on the temperature change associated to the same austenite to
      martensite transformation depending on whether it occurs on heating (retained) or
      on cooling is attributed to the predominance of the magnetic or the vibrational
      entropy terms, respectively.

PMID- 29042660
TI  - Composition-dependent nanoelectronics of amido-phenazines: non-volatile RRAM and
      WORM memory devices.
AB  - A metal-free three component cyclization reaction with amidation is devised for
      direct synthesis of DFT-designed amido-phenazine derivative bearing noncovalent
      gluing interactions to fabricate organic nanomaterials. Composition-dependent
      organic nanoelectronics for nonvolatile memory devices are discovered using mixed
      phenazine-stearic acid (SA) nanomaterials. We discovered simultaneous two
      different types of nonmagnetic and non-moisture sensitive switching resistance
      properties of fabricated devices utilizing mixed organic nanomaterials: (a)
      sample-1(8:SA = 1:3) is initially off, turning on at a threshold, but it does not
      turn off again with the application of any voltage, and (b) sample-2 (8:SA = 3:1)
      is initially off, turning on at a sharp threshold and off again by reversing the
      polarity. No negative differential resistance is observed in either type. These
      samples have different device implementations: sample-1 is attractive for write
      once-read-many-times memory devices, such as novel non-editable database,
      archival memory, electronic voting, radio frequency identification, sample-2 is
      useful for resistive-switching random access memory application.

PMID- 29042661
TI  - Therapy of corneal endothelial dysfunction with corneal endothelial cell-like
      cells derived from skin-derived precursors.
AB  - Corneal endothelial dysfunction occurs when corneal endothelial cells (CECs) are
      dramatically lost and eventually results in vision loss. Corneal transplantation
      is the only solution at present. However, corneal transplantation requires a
      fresh human cornea and there is a worldwide shortage of donors. Therefore,
      finding new functional CECs to replace human CECs is urgent. Skin-derived
      precursors (SKPs) can be easily acquired and have multiple differential
      potential. We co-cultured human SKPs with B4G12 cells in serum-free medium and
      obtained abundant CEC-like cells which had similar morphology and characteristic
      to human CECs. CEC-like cells exerted excellent therapeutic effect when they were
      transplanted into rabbit and monkey corneal endothelial dysfunction models by
      injection method. This protocol enables efficient production of CEC-like cells
      from SKPs. The renewable cell source, novel derivation method and simple
      treatment strategy may lead to potential applications in cell replacement therapy
      for corneal endothelial dysfunction.

PMID- 29042662
TI  - Switching to PegIFNalpha-2b leads to HBsAg loss in patients with low HBsAg levels
      and HBV DNA suppressed by NAs.
AB  - Patients with low hepatitis B surface antigen (HBsAg) levels and hepatitis B
      virus (HBV) DNA suppression by nucleos(t)ide analogues (NAs) achieve high rate of
      HBsAg loss through switching to PegIFNalpha in pre-registration study. The aim of
      this study was to achieve higher rate of HBsAg loss through extended PegIFN
      treatment. 98 patients with HBsAg < 2,000 IU/ml and HBV DNA < 20 IU/ml were
      randomized to receive PegIFNalpha-2b or continuing NA therapy for 60 weeks. At
      the end of treatment (EOT) and end of follow-up (EOF), only patients who switched
      to PegIFNalpha-2b achieved HBsAg loss (32.6%) and HBsAg seroconversion (27.9% and
      25.6%). Patients who switched to PegIFNalpha-2b also achieved higher HBeAg
      seroconversion rates (65.1%) and HBeAg loss (81.4% and 90.7%) than those who
      continued NAs treatment. On-treatment HBsAg declines predicted the responses at
      EOT, and HBsAg declines at post-baseline times predicted the responses at EOF.
      The rates of responses were not increased through extended PegIFNalpha treatment.
      For patients with low HBsAg and HBV suppression with NAs, switching to
      PegIFNalpha-2b significantly increased the rates of HBsAg loss and HBsAg
      seroconversion. HBsAg decline can predict the response of switching to
      PegIFNalpha-2b following from NAs.

PMID- 29042663
TI  - Comparative analysis of molecular and physiological traits between perennial
      Arabis alpina Pajares and annual Arabidopsis thaliana Sy-0.
AB  - Annual plants complete life cycle in a year while perennial plants maintain
      growth for several years. Arabis alpina, a polycarpic perennial, is a close
      relative of monocarpic annual Arabidopsis. Pajares is an accession of A. alpina
      requiring vernalization, a long-term cold for flowering. Arabidopsis shows
      holistic flowering whereas Pajares shows idiographic flowering, producing
      axillary branches under variable developmental phases from juvenile, adult
      vegetative to reproductive phases. To understand the molecular mechanism behind
      diverse phases of axillary branches, we analyzed the levels of primary miR156
      expressions because miR156-SPL module is a key regulator for developmental phase
      transition. We found that in Pajares, miR156 levels were highly variable among
      the axillary branches, which causes differential sensitivity to vernalization.
      Thus, the axillary branches expressing high levels of miR156 remain in juvenile
      phase even after vernalization, whereas the axillary branches expressing low
      levels of miR156 produce flowers after vernalization. In contrast, every axillary
      branches of Arabidopsis winter annual Sy-0 expressed similar levels of miR156 and
      synchronously responded to vernalization, which causes holistic flowering.
      Therefore, we suggest that variable miR156 expression levels and the resulting
      differential response to vernalization among axillary branches are distinctive
      features determining polycarpic perenniality of A. alpina Pajares.

PMID- 29042664
TI  - Cationic double K-hole pre-edge states of CS2 and SF6.
AB  - Recent advances in X-ray instrumentation have made it possible to measure the
      spectra of an essentially unexplored class of electronic states associated with
      double inner-shell vacancies. Using the technique of single electron
      spectroscopy, spectra of states in CS2 and SF6 with a double hole in the K-shell
      and one electron exited to a normally unoccupied orbital have been obtained. The
      spectra are interpreted with the aid of a high-level theoretical model giving
      excellent agreement with the experiment. The results shed new light on the
      important distinction between direct and conjugate shake-up in a molecular
      context. In particular, systematic similarities and differences between pre-edge
      states near single core holes investigated in X-ray absorption spectra and the
      corresponding states near double core holes studied here are brought out.

PMID- 29042665
TI  - GDC-0449 improves the antitumor activity of nano-doxorubicin in pancreatic cancer
      in a fibroblast-enriched microenvironment.
AB  - Pancreatic cancer is one of the most lethal human cancers that currently does not
      have effective therapies. Novel treatments including nanomedicines and
      combination therapies are thus urgently needed for these types of deadly
      diseases. A key feature of pancreatic cancer is its tumor protective dense
      stroma, which is generated by cancer-associated fibroblasts (CAFs). The
      interaction between CAFs and pancreatic cancer cells abnormally activates sonic
      hedgehog (SHH) signaling and facilitates tumor growth, metastasis, and drug
      resistance. Here, we report that the commercial SHH inhibitor GDC-0449 reverses
      fibroblast-induced resistance to doxorubicin in Smoothened (SMO)-positive
      pancreatic cancer cells by downregulating SHH signaling proteins. Importantly,
      the synergistic combination of GDC-0449 with PEG-PCL-Dox exhibited potent
      antitumor efficacy in a BxPC-3 tumor xenograft model, whereas single treatments
      did not significantly inhibit tumor growth. Our findings reveal a potential
      treatment strategy for fibroblast-enriched pancreatic cancer.

PMID- 29042666
TI  - Equation of state and self-bound droplet in Rabi-coupled Bose mixtures.
AB  - Laser induced transitions between internal states of atoms have been playing a
      fundamental role to manipulate atomic clouds for many decades. In absence of
      interactions each atom behaves independently and their coherent quantum dynamics
      is described by the Rabi model. Since the experimental observation of Bose
      condensation in dilute gases, static and dynamical properties of multicomponent
      quantum gases have been extensively investigated. Moreover, at very low
      temperatures quantum fluctuations crucially affect the equation of state of many
      body systems. Here we study the effects of quantum fluctuations on a Rabi-coupled
      two-component Bose gas of interacting alkali atoms. The divergent zero-point
      energy of gapless and gapped elementary excitations of the uniform system is
      properly regularized obtaining a meaningful analytical expression for the beyond
      mean-field equation of state. In the case of attractive inter-particle
      interaction we show that the quantum pressure arising from Gaussian fluctuations
      can prevent the collapse of the mixture with the creation of a self-bound
      droplet. We characterize the droplet phase and discover an energetic instability
      above a critical Rabi frequency provoking the evaporation of the droplet.
      Finally, we suggest an experiment to observe such quantum droplets using Rabi
      coupled internal states of K39 atoms.

PMID- 29042667
TI  - MG-132 reduces virus release in Bovine herpesvirus-1 infection.
AB  - Bovine herpesvirus 1 (BoHV-1) can provoke conjunctivitis, abortions and shipping
      fever. BoHV-1 infection can also cause immunosuppression and increased
      susceptibility to secondary bacterial infections, leading to pneumonia and
      occasionally to death. Herein, we investigated the influence of MG-132, a
      proteasome inhibitor, on BoHV-1 infection in bovine kidney (MDBK) cells.
      Infection of MDBK cells with BoHV-1 induces apoptotic cell death that enhances
      virus release. Whereas, MG-132 inhibited virus-induced apoptosis and stimulated
      autophagy. Protein expression of viral infected cell protein 0 (bICP0), which is
      constitutively expressed during infection and is able to stimulate Nuclear factor
      kappa B (NF-kappaB), was completely inhibited by MG-132. These results were
      accompanied by a significant delay in the NF-kappaB activation. Interestingly,
      the efficient virus release provoked by BoHV-1-induced apoptosis was
      significantly reduced by MG-132. Overall, this study suggests that MG-132,
      through the activation of autophagy, may limit BoHV-1 replication during
      productive infection, by providing an antiviral defense mechanism.

PMID- 29042668
TI  - Signalling mechanisms in PAF-induced intestinal failure.
AB  - Capillary leakage syndrome, vasomotor disturbances and gut atony are common
      clinical problems in intensive care medicine. Various inflammatory mediators and
      signalling pathways are involved in these pathophysiological alterations among
      them platelet-activating factor (PAF). The related signalling mechanisms of the
      PAF-induced dysfunctions are only poorly understood. Here we used the model of
      the isolated perfused rat small intestine to analyse the role of calcium (using
      calcium deprivation, IP-receptor blockade (2-APB)), cAMP (PDE-inhibition plus AC
      activator), myosin light chain kinase (inhibitor ML-7) and Rho-kinase (inhibitor
      Y27632) in the following PAF-induced malfunctions: vasoconstriction, capillary
      and mucosal leakage, oedema formation, malabsorption and atony. Among these, the
      PAF-induced vasoconstriction and hyperpermeability appear to be governed by
      similar mechanisms that involve IP3 receptors, extracellular calcium and the Rho
      kinase. Our findings further suggest that cAMP-elevating treatments - while
      effective against hypertension and oedema - bear the risk of dysmotility and
      reduced nutrient uptake. Agents such as 2-APB or Y27632, on the other hand,
      showed no negative side effects and improved most of the PAF-induced malfunctions
      suggesting that their therapeutic usefulness should be explored.

PMID- 29042669
TI  - RNA editing by ADAR1 regulates innate and antiviral immune functions in primary
      macrophages.
AB  - ADAR1-dependent A-to-I editing has recently been recognized as a key process for
      marking dsRNA as self, therefore, preventing innate immune activation and
      affecting the development and resolution of immune-mediated diseases and
      infections. Here, we have determined the role of ADAR1 as a regulator of innate
      immune activation and modifier of viral susceptibility in primary myeloid and
      lymphoid cells. We show that ADAR1 knockdown significantly enhanced interferon,
      cytokine and chemokine production in primary macrophages that function as
      antiviral paracrine factors, rendering them resistant to HIV-1 infection. ADAR1
      knockdown induced deregulation of the RLRs-MAVS signaling pathway, by increasing
      MDA5, RIG-I, IRF7 and phospho-STAT1 expression, an effect that was partially
      rescued by pharmacological blockade of the pathway. In summary, our results
      demonstrate a role of ADAR1 in regulating innate immune function in primary
      macrophages, suggesting that macrophages may play an essential role in disease
      associated to ADAR1 dysfunction. We also show that viral inhibition is
      exclusively dependent on innate immune activation consequence of ADAR1 knockdown,
      pointing towards ADAR1 as a potential target to boost antiviral immune response.

PMID- 29042670
TI  - From EST to novel spider silk gene identification for production of spidroin
      based biomaterials.
AB  - A cDNA library from a pool of all the seven silk glands from a tropical spider
      species was constructed. More than 1000 expressed sequence tag (EST) clones were
      created. Almost 65% of the EST clones were identified and around 50% were
      annotated. The cellular and functional distribution of the EST clones indicated
      high protein synthesis activity in spider silk glands. Novel clones with
      repetitive amino acid sequences, which is one of the most important
      characteristics of spider silk genes, were isolated. One of these clones, namely
      TuSp2 in current research, contains two almost identical fragments with one short
      C-terminal domain. Reverse transcription (RT) PCR and expression analysis showed
      that it is expressed in the tubuliform gland and involved in eggcase silk
      formation. Furthermore, its single repetitive domain can be induced to form
      various types of materials, including macroscopic fibers, transparent film and
      translucent hydrogel. This study implies promising potentials for future
      identification of novel spidroins and development of new spidroin-based
      biomaterials.

PMID- 29042671
TI  - Credit assignment between body and object probed by an object transportation
      task.
AB  - It has been proposed that learning from movement errors involves a credit
      assignment problem: did I misestimate properties of the object or those of my
      body? For example, an overestimate of arm strength and an underestimate of the
      weight of a coffee cup can both lead to coffee spills. Though previous studies
      have found signs of simultaneous learning of the object and of the body during
      object manipulation, there is little behavioral evidence about their quantitative
      relation. Here we employed a novel weight-transportation task, in which
      participants lift the first cup filled with liquid while assessing their learning
      from errors. Specifically, we examined their transfer of learning when switching
      to a contralateral hand, the second identical cup, or switching both hands and
      cups. By comparing these transfer behaviors, we found that 25% of the learning
      was attributed to the object (simply because of the use of the same cup) and 58%
      of the learning was attributed to the body (simply because of the use of the same
      hand). The nervous system thus seems to partition the learning of object
      manipulation between the object and the body.

PMID- 29042672
TI  - Bio-based coatings for reducing water sorption in natural fibre reinforced
      composites.
AB  - In this study, bio-based coatings were used for reducing water sorption of
      composites containing flame retardant treated natural fibres and phenolic resin.
      Two types of coatings; polyfurfuryl alcohol resin (PFA) and polyurethane (PU)
      were used on the composites and compared with a water resistant market product.
      Uncoated and coated samples were conditioned at 90  degrees C and relative
      humidity of 90% for three days and the relative moisture content and mechanical
      properties after conditioning were analysed. In addition, the changes in the
      weight loss of the conditioned samples were also investigated by
      thermogravimetric analysis. The moisture diffusion characteristics of coated
      laminates were also studied at room temperature under water immersion conditions.
      PFA coated samples showed better moisture resistance and mechanical performance
      than other bio-based coatings when subjected to long term environmental aging.

PMID- 29042673
TI  - Simultaneous hydrolysis of carbaryl and chlorpyrifos by Stenotrophomonas sp.
      strain YC-1 with surface-displayed carbaryl hydrolase.
AB  - Many sites are often co-contaminated with multiple pesticides. To date, there are
      no reports on simultaneous degradation of different classes of pesticides by a
      natural microorganism. In this work, we aim at constructing a live biocatalyst
      able to simultaneously hydrolyze carbaryl and chlorpyrifos. For this purpose,
      carbaryl hydrolase (CH) was displayed on the cell surface of a chlorpyrifos
      degrading bacterium Stenotrophomonas sp. strain YC-1 using N- and C-terminal
      domain of ice nucleation protein (INPNC) from Pseudomonas syringae INA5 as an
      anchoring motif. The localization of INPNC-CH fusion protein in the outer
      membrane fraction was demonstrated by cell fractionation followed by Western blot
      analysis. Surface display of INPNC-CH was further confirmed by proteinase
      accessibility experiment and immunofluorescence microscope. CH was present in an
      active form on cell surface without causing any growth inhibition, suggesting
      that the INP-based display system is a useful tool for surface expression of
      macromolecular heterologous proteins on the bacterial cell surface. Because
      surface-displayed CH has free access to pesticides, this bacterium can be used as
      a whole-cell biocatalyst for efficient hydrolysis of pesticides.

PMID- 29042674
TI  - Knockout of maternal CD163 protects fetuses from infection with porcine
      reproductive and respiratory syndrome virus (PRRSV).
AB  - After infection of the porcine dam at about 90 days of gestation, porcine
      reproductive and respiratory syndrome virus (PRRSV) crosses the placenta and
      begins to infect fetuses. Outcomes of include abortion, fetal death and
      respiratory disease in newborn piglets. CD163 is the receptor for the virus. In
      this study, CD163-positive fetuses, recovered between 109 days of gestation or 20
      days after maternal infection, were completely protected from PRRSV in dams
      possessing a complete knockout of the CD163 receptor. The results demonstrate a
      practical means to eliminate PRRSV-associated reproductive disease, a major
      source of economic hardship to agriculture.

PMID- 29042675
TI  - Optical switching of defect charge states in 4H-SiC.
AB  - We demonstrate optically induced switching between bright and dark charged
      divacancy defects in 4H-SiC. Photoluminescence excitation and time-resolved
      photoluminescence measurements reveal the excitation conditions for such charge
      conversion. For an energy below 1.3 eV (above 950 nm), the PL is suppressed by
      more than two orders of magnitude. The PL is recovered in the presence of a
      higher energy repump laser with a time-averaged intensity less than 0.1% that of
      the excitation field. Under a repump of 2.33 eV (532 nm), the PL increases
      rapidly, with a time constant 30 MUs. By contrast, when the repump is switched
      off, the PL decreases first within 100-200 MUs, followed by a much slower decay
      of a few seconds. We attribute these effect to the conversion between two
      different charge states. Under an excitation at energy levels below 1.3 eV,
      VSiVC0 are converted into a dark charge state. A repump laser with an energy
      above 1.3 eV can excite this charged state and recover the bright neutral state.
      This optically induced charge switching can lead to charge-state fluctuations but
      can be exploited for long-term data storage or nuclear-spin-based quantum memory.

PMID- 29042676
TI  - Semiochemical mediated enhancement of males to complement sterile insect
      technique in management of the tephritid pest Bactrocera tryoni (Froggatt).
AB  - Queensland fruit fly, Bactrocera tryoni (Froggatt), is the most significant pest
      of Australia's $9 billion horticulture industry. The sterile insect technique
      (SIT) and cue-lure (a synthetic analogue of raspberry ketone (RK))-based male
      annihilation technique (MAT) are two of the most effective management tools
      against this pest. However, combining these two approaches is considered
      incompatible as MAT kills sterile and 'wild' males indiscriminately. In the
      present study we tested the effect of pre-release feeding of B. tryoni on RK on
      their post-release survival and response to MAT in field cages and in a
      commercial orchard. In both settings, survival was higher for RK supplemented
      adults compared to control (i.e. RK denied) adults. A lower number of RK
      supplemented sterile males were recaptured in MAT baited traps in both the field
      cages and orchard trials compared to RK denied sterile males. The advantage of
      this novel "male replacement" approach (relatively selective mortality of wild
      males at lure-baited traps while simultaneously releasing sterile males) is
      increasing the ratio of sterile to wild males in the field population, with
      potential for reducing the number of sterile males to be released.

PMID- 29042677
TI  - High resolution, high speed, long working distance, large field of view confocal
      fluorescence microscope.
AB  - Confocal fluorescence microscopy is often used in brain imaging experiments,
      however conventional confocal microscopes are limited in their field of view,
      working distance, and speed for high resolution imaging. We report here the
      development of a novel high resolution, high speed, long working distance, and
      large field of view confocal fluorescence microscope (H2L2-CFM) with the
      capability of multi-region and multifocal imaging. To demonstrate the concept, a
      0.5 numerical aperture (NA) confocal fluorescence microscope is prototyped with a
      3 mm * 3 mm field of view and 12 mm working distance, an array of 9 beams is
      scanned over the field of view in 9 different regions to speed up the acquisition
      time by a factor of 9. We test this custom designed confocal fluorescence
      microscope for future use with brain clarification methods to image large volumes
      of the brain at subcellular resolution. This multi-region and multi-spot imaging
      method can be used in other imaging modalities, such as multiphoton microscopes,
      and the field of view can be extended well beyond 12 mm * 12 mm.

PMID- 29042678
TI  - Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion
      and glucose uptake.
AB  - The worldwide prevalence of diabetes has risen to 8.5% among adults, which
      represents a staggering rise in prevalence from 4.7% in 1980. Whilst some
      treatments work by increasing insulin secretion, over time their effectiveness
      decreases. We aim to increase insulin secretion by developing strategies that
      work through mechanisms independent of current treatment options. Isolated CD1
      mouse islets, INS-1 pancreatic beta-cells, or C2C12 mouse myotubes were incubated
      in standard tissue culture media, or media supplemented with 28 mM glucose, 200
      MUM palmitic acid, and 200 MUM oleic acid as a cellular model of diabetic
      glucolipotoxicity. Intracellular reactive species content was assayed using 2',7'
      dichlorofluorescein diacetate dye, inducible nitric oxide synthase levels
      determined by Western blot, 3-nitrotyrosine and 4-hydrpxnonenal both assayed by
      ELISA, insulin secretion quantified using ELISA or radioimmunoassay, and glucose
      uptake determined through 2-deoxy glucose 6 phosphate luminescence. Our data
      indicate that carnosine, a histidine containing dipeptide available through the
      diet, is an effective scavenger of each of the aforementioned reactive species.
      This results in doubling of insulin secretion from isolated mouse islets or INS-1
      beta-cells. Crucially, carnosine also reverses glucolipotoxic inhibition of
      insulin secretion and enhances glucose uptake into skeletal muscle cells. Thus,
      carnosine, or non-hydrolysable carnosine analogs, may represent a new class of
      therapeutic agent to fight type 2 diabetes.

PMID- 29042679
TI  - Municipal sewage sludge compost promotes Mangifera persiciforma tree growth with
      no risk of heavy metal contamination of soil.
AB  - Application of sewage sludge compost (SSC) as a fertilizer on landscaping
      provides a potential way for the effective disposal of sludge. However, the
      response of landscape trees to SSC application and the impacts of heavy metals
      from SSC on soil are poorly understood. We conducted a pot experiment to
      investigate the effects of SSC addition on Mangifera persiciforma growth and
      quantified its uptake of heavy metals from SSC by setting five treatments with
      mass ratios of SSC to lateritic soil as 0%:100% (CK), 15%:85% (S15), 30%:70%
      (S30), 60%:40% (S60), and 100%:0% (S100). As expected, the fertility and heavy
      metal concentrations (Cu, Zn, Pb and Cd) in substrate significantly increased
      with SSC addition. The best performance in terms of plant height, ground
      diameter, biomass and N, P, K uptake were found in S30, implying a reasonable
      amount of SSC could benefit the growth of M. persiciforma. The concentrations of
      Cu, Pb and Cd in S30 were insignificantly different from CK after harvest,
      indicating that M. persiciforma reduced the risk of heavy metal contamination of
      soil arising from SSC application. This study suggests that a reasonable rate of
      SSC addition can enhance M. persiciforma growth without causing the contamination
      of landscaping soil by heavy metals.

PMID- 29042680
TI  - Sperm-borne miR-449b influences cleavage, epigenetic reprogramming and apoptosis
      of SCNT embryos in bovine.
AB  - Accumulating evidence indicates the absence of paternally derived miRNAs,
      piwiRNAs, and proteins may be one important factor contributing to developmental
      failure in somatic cell cloned embryos. In the present study, we found microRNA
      449b (miR-449b) was highly expressed in sperm. Target gene predictions and
      experimental verification indicate that several embryonic development-related
      genes, including CDK6, c-MYC, HDAC1 and BCL-2, are targets of miR-449b. We
      therefore investigated the role of miR-449b using somatic cell nuclear transfer
      (SCNT) embryo model. Bovine fetal fibroblasts, expressing miR-449b through a
      doxycycline (dox) induced expression system were used as nuclear donor cells for
      SCNT. The results showed that miR-449b expression in SCNT embryos significantly
      enhanced the cleavage rate at 48 h after activation and the levels of H3K9
      acetylation at the 2-cell to 8-cell stages, meanwhile, significantly decreased
      the apoptosis index of blastocysts. In addition, we verified miR-449b could
      regulate the expression levels of CDK6, c-MYC, HDAC1 and BCL-2. In conclusion,
      the present study shows that miR-449b expression improves the first cleavage
      division, epigenetic reprogramming and apoptotic status of bovine preimplantation
      cloned embryos.

PMID- 29042681
TI  - The construction of intrahepatic cholangiocarcinoma model in zebrafish.
AB  - Intrahepatic cholangiocarcinoma (ICC) is a highly malignant tumor, difficult to
      diagnose even at an early stage. In this study, we successfully constructed an
      nras 61K -induced ICC model in zebrafish. Transcriptome analysis and gene set
      enrichment analysis (GSEA) of liver samples of the ICC and WT (wild-type)
      zebrafish revealed that the genes differentially expressed between the two groups
      were mainly involved in focal adhesion, chemokine signaling and metabolic
      pathways. Analysis of DNA methylomes revealed that compared with WT samples,
      methylated genes in ICC samples were enriched in functions associated with
      cellular, single-organism and metabolic processes. In particular, our result
      discovered eleven potential biomarker genes of ICC which were conserved between
      zebrafish and humans. Moreover, three potential biomarker genes were
      hypomethylated in the tumorigenesis of ICC: ehf, epha4 and itgb6. In summary, our
      study provides a comprehensive analysis of molecular mechanisms accompanying the
      progressive nras 61K -induced ICC. This work indicates that our transgenic
      zebrafish could be a valuable model, not only for studying liver cancer, but also
      for exploring new therapeutic targets.

PMID- 29042683
TI  - Hormone Signaling Regulates Nymphal Diapause in Laodelphax striatellus
      (Hemiptera: Delphacidae).
AB  - Diapause is a physiological adaptation that allows an organism to survive adverse
      environmental conditions. Diapause occurs at a specific developmental stage in
      each species. There are few reports regarding the molecular regulatory mechanism
      of nymphal diapause in Laodelphax striatellus, which is an important graminaceous
      crop pest. Our previous studies identified the conditions for nymphal diapause in
      this species. Here, we combined RNA sequencing transcriptomics and quantitative
      proteomic analyses to identify nymphal diapause-related genes and proteins. The
      analysis of differentially regulated genes identified four gene/protein pairs
      that were synchronously up-regulated, and six gene/protein pairs that were
      synchronously down-regulated, suggesting that these genes may regulate nymphal
      diapause. The up-regulated gene juvenile hormone acid methyl transferase (JHAMT)
      and the down-regulated gene cytochrome P450 monooxygenase (CYP314A1, Shd) were
      chosen for further functional studies. After knocking-down of LsJHAMT and LsShd
      in vivo by RNA interference, the titer of JH III and 20E decreased significantly,
      and the duration of the nymphal development period was severely altered. Thus
      LsJHAMT and LsShd regulated JH III and 20E titers in the hemolymph to control the
      nymphal diapause status. This study may lead to new information on the regulation
      nymphal diapause of this important agricultural insect pest.

PMID- 29042682
TI  - IL-12 stimulates CTLs to secrete exosomes capable of activating bystander CD8+ T
      cells.
AB  - An effective cytotoxic T lymphocyte (CTL) response against intracellular
      pathogens is generally accomplished by immense CTL expansion and activation,
      which can destroy infected cells. Vigorous immune responses can lead to
      activation of bystander CD8+ T cells, but the contribution from antigen-specific
      CTLs is not well understood. We found that CTLs secrete extracellular vesicles
      following antigen stimulation. These CTL-derived vesicles contain CTL proteins
      and exhibit markers and size profiles consistent with exosomes. Interestingly,
      further stimulation of CTLs with IL-12 impacts exosome size and leads to
      selective enrichment of certain exosomal proteins. More important, exosomes from
      IL-12-stimulated CTLs directly activated bystander naive CD8+ T cells to produce
      interferon-gamma (IFNgamma) and granzyme B (GZB) in the absence of antigens,
      whereas control exosomes derived from antigen-stimulated CTLs did not. In
      addition, IL-12 induced exosomes are able to strengthen the effects of weak
      antigen stimulation on CTLs. Proteomic analysis demonstrates that IL-12
      stimulation alters catalytic and binding activities of proteins in CTL exosomes.
      Our findings indicate that the biological function and morphology of exosomes
      secreted by CTLs can be influenced by the type of stimulation CTLs receive. Thus,
      a fully functional, ongoing, antigen-specific CTL response may influence
      bystander CD8+ T cells through secretion of exosomes.

PMID- 29042685
TI  - Cancer: Growth restriction.

PMID- 29042686
TI  - Glia: Pulling in opposite directions.

PMID- 29042684
TI  - A single point mutation in class III ribonucleotide reductase promoter renders
      Pseudomonas aeruginosa PAO1 inefficient for anaerobic growth and infection.
AB  - Pseudomonas aeruginosa strain PAO1 has become the reference strain in many
      laboratories. One enzyme that is essential for its cell division is the
      ribonucleotide reductase (RNR) enzyme that supplies the deoxynucleotides required
      for DNA synthesis and repair. P. aeruginosa is one of the few microorganisms that
      encodes three different RNR classes (Ia, II and III) in its genome, enabling it
      to grow and adapt to diverse environmental conditions, including during
      infection. In this work, we demonstrate that a lack of RNR activity induces cell
      elongation in P. aeruginosa PAO1. Moreover, RNR gene expression during
      anaerobiosis differs among P. aeruginosa strains, with class III highly expressed
      in P. aeruginosa clinical isolates relative to the laboratory P. aeruginosa PAO1
      strain. A single point mutation was identified in the P. aeruginosa PAO1 strain
      class III RNR promoter region that disrupts its anaerobic transcription by the
      Dnr regulator. An engineered strain that induces the class III RNR expression
      allows P. aeruginosa PAO1 anaerobic growth and increases its virulence to
      resemble that of clinical strains. Our results demonstrate that P. aeruginosa
      PAO1 is adapted to laboratory conditions and is not the best reference strain for
      anaerobic or infection studies.

PMID- 29042687
TI  - Cognitive neuroscience: Spatial navigation takes two.

PMID- 29042688
TI  - Neurodegeneration: An independent route to toxicity.

PMID- 29042689
TI  - Behavioural neuroscience: Fighting females.

PMID- 29042691
TI  - Gastric cancer: The gastric microbiota - bacterial diversity and implications.

PMID- 29042692
TI  - NAFLD: HIF2alpha: a new therapeutic target for NAFLD.

PMID- 29042690
TI  - Motor cortex - to act or not to act?
AB  - The motor cortex is a large frontal structure in the cerebral cortex of eutherian
      mammals. A vast array of evidence implicates the motor cortex in the volitional
      control of motor output, but how does the motor cortex exert this 'control'?
      Historically, ideas regarding motor cortex function have been shaped by the
      discovery of cortical 'motor maps' - that is, ordered representations of
      stimulation-evoked movements in anaesthetized animals. Volitional control,
      however, entails the initiation of movements and the ability to suppress
      undesired movements. In this article, we highlight classic and recent findings
      that emphasize that motor cortex neurons have a role in both processes.

PMID- 29042693
TI  - Occult Sources of Bleeding in Blunt Trauma : A Narrative Review.
AB  - Worldwide, hemorrhagic shock in major trauma remains a major potentially
      preventable cause of death. Controlling bleeding and subsequent coagulopathy is a
      big challenge. Immediate assessment of unidentified bleeding sources is essential
      in blunt trauma patients with hemorrhagic shock. Chest/pelvic X-ray in
      conjunction with ultrasonography have been established classically as initial
      diagnostic imaging modalities to identify the major sources of internal bleeding
      including intra-thoracic, intra-abdominal, or retroperitoneal hemorrhage related
      to pelvic fracture. Massive soft tissue injury, regardless of whether isolated or
      associated with multiple injuries, occasionally causes extensive hemorrhage and
      acute traumatic coagulopathy. Specific types of injuries, including soft tissue
      injury or retroperitoneal hemorrhage unrelated to pelvic fracture, can
      potentially be overlooked or be considered "occult" causes of bleeding because
      classical diagnostic imaging often cannot exclude such injuries. The purpose of
      this narrative review article is to describe "occult" or unusual sources of
      bleeding associated with blunt trauma.

PMID- 29042694
TI  - Immunohistochemistry of Vasohibin-2 in Human Kidney Disease : Implications in
      Impaired Glucose Tolerance and Reduced Renal Function.
AB  - Several angiogenesis-related factors are known to play important roles in the
      pathogenesis of kidney disease. Vasohibin-2 (VASH-2) was recently reported as a
      novel proangiogenic factor. Although VASH-2 was demonstrated to accelerate tumor
      angiogenesis, its roles in non-tumor processes including renal disease have not
      been well elucidated yet. Here, we performed a retrospective study including an
      immunohistochemical analysis of human kidney biopsy specimens from 82 Japanese
      patients with a variety of kidney diseases, and we evaluated the correlations
      between the immunoreactivity of VASH-2 and the patients' clinicopathological
      parameters. VASH-2 immunoreactivity was detected in varying degrees in renal
      tubules as well as in peritubular capillaries and vasa recta. The cortical and
      medullary tubule VASH-2+ scores were correlated with the presence of
      hypertension, and the medullary tubule VASH-2+ score was significantly correlated
      with the blood glucose (p=0.029, r=0.35) and hemoglobin A1c levels (p=0.0066,
      r=0.39). Moreover, decreased VASH-2+ scores in the vasa recta were associated
      with reduced renal function (p=0.0003). These results suggest that VASH-2 could
      play an important role in the pathogenesis of renal diseases, and that VASH-2 is
      closely associated with hypertension and impaired glucose tolerance.

PMID- 29042695
TI  - Living Donor Liver Transplantation for Acute Liver Failure : Comparing Guidelines
      on the Prediction of Liver Transplantation.
AB  - Determining the indications for and timing of liver transplantation (LT) for
      acute liver failure (ALF) is essential. The King's College Hospital (KCH)
      guidelines and Japanese guidelines are used to predict the need for LT and the
      outcomes in ALF. These guidelines' accuracy when applied to ALF in different
      regional and etiological backgrounds may differ. Here we compared the accuracy of
      new (2010) Japanese guidelines that use a simple scoring system with the 1996
      Japanese guidelines and the KCH criteria for living donor liver transplantation
      (LDLT). We retrospectively analyzed 24 adult ALF patients (18 acute type, 6 sub
      acute type) who underwent LDLT in 1998-2009 at our institution. We assessed the
      accuracies of the 3 guidelines' criteria for ALF. The overall 1-year survival
      rate was 87.5%. The new and previous Japanese guidelines were superior to the KCH
      criteria for accurately predicting LT for acute-type ALF (72% vs. 17%). The new
      Japanese guidelines could identify 13 acute-type ALF patients for LT, based on
      the timing of encephalopathy onset. Using the previous Japanese guidelines,
      although the same 13 acute-type ALF patients (72%) had indications for LT, only 4
      patients were indicated at the 1st step, and it took an additional 5 days to
      decide the indication at the 2nd step in the other 9 cases. Our findings showed
      that the new Japanese guidelines can predict the indications for LT and provide a
      reliable alternative to the previous Japanese and KCH guidelines.

PMID- 29042696
TI  - The Usefulness of Colonoscopy for the Detection of Ileal Involvement in
      Intestinal Follicular Lymphoma Patients.
AB  - To evaluate the usefulness of colonoscopy for the detection of ileal involvement
      in patients with intestinal follicular lymphoma, seventeen patients with
      intestinal follicular lymphoma who underwent colonoscopy and biopsy sampling from
      the terminal ileum were enrolled. The patients were divided into 2 groups: cases
      with ileal involvement (n=6) and cases without ileal involvement (n=11).
      Patients' clinical backgrounds were compared between the two groups.
      Subsequently, 10 board-certified endoscopists independently evaluated the
      endoscopic pictures and determined whether the ileum was involved with follicular
      lymphoma. Infiltration of follicular lymphoma cells were identified in 6 patients
      (35.3%). Cases with positive ileal involvement were diagnosed with follicular
      lymphoma at a younger age than were cases without ileal involvement (55.4+/-7.4
      vs. 68.1+/-10.3 years, p=0.011). Macroscopically, in patients with ileal
      involvement, there were multiple polypoid elevations smaller than 5 mm in 4
      cases, single polypoid elevation smaller than 5 mm in 1 case, and single polypoid
      elevation larger than 5 mm in 1 case. In patients without ileal involvement,
      there were no lesions in the terminal ileum in 7 cases, and multiple polypoid
      elevations smaller than 5 mm were seen in 4 cases. The accuracy of the
      macroscopic evaluation by 10 board-certified endoscopists was 68.8%. Colonoscopy
      is particularly recommended during the initial workup of patients with follicular
      lymphoma diagnosed at age <= 60 years. The diagnosis of ileal involvement based
      on morphology alone is difficult; thus, biopsy and pathologic diagnosis are
      required for accurate diagnosis.

PMID- 29042697
TI  - Vaginoplasty with a Pudendal-groin Flap in Male-to-female Transsexuals.
AB  - Many vaginoplasty techniques have been introduced to improve the outcomes of sex
      reassignment surgery for male-to-female transsexuals. Some vaginoplasty patients
      still require additional skin grafts, making dilation mandatory to overcome
      shrinkage. We developed a new vaginoplasty method (called the "pudendal-groin
      flap") that uses pudendal-groin flaps. One of this procedure's advantages is that
      skin grafts are unnecessary, even for patients with small penises and scrotums.
      We introduce the procedure here and describe our evaluation of its utility. We
      retrospectively analyzed the cases of the 15 patients who underwent vaginoplasty
      using pudendal-groin flaps from May 2010 to January 2016 at our institution. We
      compared the complications as well as the functional and aesthetic outcomes with
      those of previous studies. The most common complication was bleeding, which
      occurred at the corpus spongiosum or while creating a new vaginal cavity.
      Bleeding can be reduced with more careful hemostasis and dissection. Aside from
      inadequate vaginal depth in one patient, the incidence of other complications,
      sexual intercourse, and aesthetic outcomes were acceptable. The pudendal- groin
      flap is thin and pliable and can create sufficient vaginal depth without skin
      grafts. The resulting scar is inconspicuous. Our findings suggest that
      vaginoplasty using the pudendal-groin flap method is feasible.

PMID- 29042698
TI  - Evaluating Low-kV Dual-source CT Angiography by High-pitch Spiral Acquisition and
      Iterative Reconstruction in Pediatric Congenital Heart Disease Patients.
AB  - We retrospectively evaluated the qualities of pediatric cardiovascular dual
      source computed tomography (DSCT) images reconstructed by sinogram-affirmed
      iterative reconstruction (SAFIRE) and filtered back projection (FBP). We analyzed
      the cases of 287 congenital heart disease (CHD) patients < 5 years old, referred
      to our department in August 2013-March 2015. We divided them into two groups
      according to tube voltage (70 kVp, n=147; 80 kVp, n=140). All images were
      acquired by a CARE kV system and reconstructed by FBP and SAFIRE. The
      attenuation, noise, and signal-to-noise ratio (SNR) at each region of the heart
      and great vessels were measured. The volume CT dose index and dose-length product
      values were recorded. Compared to FBP, reconstruction by SAFIRE showed that the
      attenuation volume was significantly lower by 0.4% except for the ascending aorta
      (p<0.05), the noise value was lower by about 20% (p<0.05), and the SNR was higher
      by approx. 25% (p<0.05). The radiation dose in the 70 kVp group was significantly
      lower than that in the 80 kVp group. No significant differences in SNR were
      observed between the patient groups. DSCT image acquisition with SAFIRE using the
      CARE kV system results in low image noise and radiation dose in pediatric
      patients with CHD.

PMID- 29042699
TI  - Arthroscopic Repair of the Medial Meniscus Radial/Oblique Tear Prevents the
      Progression of Meniscal Extrusion in Mildly Osteoarthritic Knees.
AB  - Extrusion of the medial meniscus (MM) is associated with knee joint pain in
      osteoarthritic knees. The relationships among MM radial/oblique tears, MM
      extrusion (MME), and the effect of arthroscopic meniscal repair are not
      established. Here we evaluated the effects of arthroscopic all-inside MM repair
      on MME and the clinical outcomes in patients with radially oriented MM tears and
      mildly osteoarthritic knees. Twenty patients with a symptomatic radial or oblique
      tear of the MM posterior segment, MME >=2.5 mm, and mildly osteoarthritic knees
      were treated using FasT-Fix 360 All-inside Meniscal Suture devices. We used
      magnetic resonance imaging (MRI) to measure the patients' MM body width (MMBW),
      absolute MME, and relative MME. The Japanese Knee Injury and Osteoarthritis
      Outcome Score, Lysholm, Tegner, IKDC Subjective Knee Evaluation, and Visual
      Analogue Scale scores were obtained. Arthroscopic all-inside MM repair prevented
      increases of absolute and relative MME. The preoperative and 3- and 12-month MRI
      based MMBW values were similar. Over a 24-month follow-up after the MM repairs,
      the clinical scores showed significant improvements. Our results suggest that all
      inside meniscal repairs would be useful in preventing the progression of MME in
      patients suffering from symptomatic MM radial/oblique tears associated with
      mildly osteoarthritic knees.

PMID- 29042700
TI  - Preoperative Risk Factors for Conversion of Laparoscopic Cholecystectomy to Open
      Cholecystectomy and the Usefulness of the 2013 Tokyo Guidelines.
AB  - To identify predictive factors for conversion from laparoscopic cholecystectomy
      (LC) to open cholecystectomy performed for mixed indications as an acute or
      elective procedure. We retrospectively analyzed the data of 236 consecutive cases
      of LC performed in our department between January 2012 and January 2015, and
      evaluated preoperative risk factors for conversion and the usefulness of the 2013
      Tokyo guidelines (TG2013) for diagnosing acute cholecystitis. The conversion rate
      in our series was 8% (19/236 cases). The following independent predictive factors
      of conversion were identified (p<=0.04): previous upper abdominal surgery (odds
      ratio (OR), 14.6), pericholecystic fluid (OR, 10.04), acute cholecystitis (OR,
      7.81), and emergent LC (OR, 15.8). Specifically for patients with acute
      cholecystitis defined using the 2013 Tokyo guidelines, use of an antiplatelet or
      anticoagulant drug for cardiovascular disease (p=0.043), previous upper abdominal
      surgery (p<0.031) and a resident as operator (p=0.041) were predictive factors.
      The risk factors for conversion identified herein could help to predict the
      difficulty of the procedure and could be used by surgeons to better inform
      patients regarding the risks for conversion. The TG2013 can be an effective tool
      for diagnosing acute cholecystitis to make informed clinical decisions regarding
      the optimal procedure for a patient.

PMID- 29042701
TI  - Direct Damage to a Vertebral Artery Better Predicts a Vertebral Artery Injury
      than Elongation in Cervical Spine Dislocation.
AB  - Cervical spine dislocation and fracture of a transverse process are isolated risk
      factors for vertebral artery injuries (VAIs), which can cause a life-threatening
      ischemic stroke. Since in vivo experiments are not possible, it has not been
      unclear whether damage to or extension of vertebral arteries is more predictive
      of a VAI. To identify the imaging characteristics associated with VAI, we
      analyzed 36 vertebral arteries from 22 cervical spine dislocation patients who
      underwent computed tomography angiography (Aug. 2008-Dec. 2014). We evaluated (1)
      the posttraumatic elongation of the vertebral artery and (2) the presence of
      fracture involving the transverse foramen. VAI was found in 20 (56%) of the 36
      vertebral arteries. The rate of residual shift (vertebral artery elongation) was
      not markedly different between the VAI and no-VAI groups. However, the rate of >1
      mm displacement into the foramen and that of fracture with gross displacement
      (>=2 mm) differed significantly between the groups. We found that greater
      displacement of fractured transverse processes with cervical spine dislocation
      was a risk factor for VAI. These results suggest that direct damage to the
      vertebral arteries by transverse process fragments is more likely to predict a
      VAI compared to elongation, even in cervical spine dislocation.

PMID- 29042702
TI  - Genetic Factors of Low-responsiveness to Hepatitis B Virus Vaccine Confirms the
      Importance of Human Leukocyte Antigen Class II Types in a Japanese Young Adult
      Population.
AB  - We investigated the genetic mechanisms underlying the association between human
      leukocyte antigen (HLA) types and the immune response to hepatitis B virus (HBV)
      vaccination in 84 healthy Japanese adults, and found that the HLA-DRB1*04 and HLA
      DQB1*03 frequencies were higher in the low responders (<10 mIU/ml; n=9, 10.7%)
      compared to the responders (>=10 mIU/ml, n=75, 89.3%). The combination of DRB1*04
      and DQB1*03 was associated with a low response to vaccination. The DRB1*04 and
      DQB1*03 haplotypes' frequencies were significantly higher in the low responders
      compared to responders. Novel candidate HLA types may be important in Japanese
      individuals.

PMID- 29042703
TI  - Modification of Dentofacial Growth Associated with Goldenhar Syndrome.
AB  - The rare developmental defect, Goldenhar syndrome is characterized by complex
      craniofacial and dentofacial anomalies. Here we describe the successful
      orthodontic treatment of a 5-year-old Japanese Goldenhar syndrome patient with
      mild facial asymmetry, right microtia, right-side hearing loss, and tongue
      thrusting by a modification of dentofacial growth using a non-surgical orthopedic
      treatment approach. Improvement of the vertical discrepancies on the affected
      side and canted occlusal plane as well as mandibular deviation were achieved with
      a functional orthopaedic approach. Stable and acceptable occlusion were obtained
      over the 32-month post-retention period. A non-surgical orthodontic treatment
      approach offers satisfactory facial aesthetic outcomes in Goldenhar syndrome.

PMID- 29042704
TI  - Alternative to Rituximab Therapy for a Patient with Ankylosing Spondylitis Who
      Was Unable to Continue Anti-TNF Therapy.
AB  - We herein present a case of a 38-year-old man who had bamboo spine and severe
      sacroiliitis and who was diagnosed with ankylosing spondylitis (AS). Infliximab
      (IFX) markedly improved the axial symptom but was discontinued due to the side
      effect of peripheral neuropathy. Switching from IFX to etanercept worsened the
      side effect. Rituximab (RTX) administration elicited a good response without side
      effects. RTX might be a suitable option for AS therapy when TNF inhibitors are
      difficult to use.

PMID- 29042705
TI  - Ureterolithotripsy for a Ureteral Calculus at the Ureteroureterostomy of a Renal
      transplant Recipient.
AB  - We describe a 40-year-old living-donor renal-transplant recipient who underwent
      successful ureterolithotripsy. He had been on hemodialysis for >15 years pre
      transplant and underwent ureteroureterostomy along with the surgery. One year
      post-transplant, ultrasound examination demonstrated hydronephrosis, and CT
      showed a 6-mm ureteral calculus at the ureteroureterostomy site. No pain and no
      elevated serum creatinine were present. As the ureter was easily accessed, we
      performed a ureterolithotripsy, which would confirm whether a suture caused the
      calculus. Despite ureteral tortuosity, laser stone fragmentation succeeded. The
      calculus was completely removed with an antegrade guidewire. Mild postoperative
      ureteral stenosis resolved with a temporary ureteral stent without balloon
      dilation. Ureterolithotripsy is effective even in renal transplant recipients
      with ureteroureterostomy.

PMID- 29042706
TI  - Protective Effects of Bisoprolol against Acute Exacerbation in Moderate-to-Severe
      Chronic Obstructive Pulmonary Disease.
AB  - Although recent retrospective studies suggested that the use of beta-blockers
      appears to help improve the mortality rate and decrease the rate of exacerbation
      in chronic obstructive pulmonary disease (COPD) patients with heart failure, the
      effects of beta-blockers on COPD patients without heart failure have not been
      established. Based on previous reports, we have launched a multicenter,
      prospective, single-arm phase II study to evaluate the preventive effect of the
      cardioselective beta-blocker bisoprolol in COPD exacerbation, in Japanese
      individuals with moderate-to-severe COPD who do not have heart failure but do
      have hypertension requiring the use of medication. The primary endpoint is the
      rate of mild-to-severe COPD exacerbation. The results of this study will clarify
      whether bisoprolol can prevent exacerbation in COPD patients without heart
      failure.

PMID- 29042707
TI  - The effect of subglottic secretion drainage on the incidence of ventilator
      associated pneumonia.
AB  - BACKGROUND: Ventilator-Associated Pneumonia (VAP) is an undesired side effect of
      mechanical ventilation in intensive care units (ICUs). AIM: We evaluated whether
      endotracheal tubes with subglottic secretion drainage (SSD) would reduce the
      incidence of VAP among patients undergoing mechanical ventilation in an ICU.
      METHODS: The analysis of medical records of patients undergoing mechanical
      ventilation exceeding 48 h who were hospitalised in ICUs between 2007 and 2014
      led to separating two groups of patients: those in whom no subglottic drainage
      was applied (NSSD) (records dating from 2007-2010) and those whose treatment
      involved endotracheal tubes with subglottic secretion drainage (SSD) (records
      dating from 2011-2014). RESULTS: Analysis of 1807 patients hospitalised in ICUs
      (804 NSSD patients and 1003 SSD patients). A difference was found in the
      frequency of VAP incidence between the groups (P<0.001). In the NSSD group as
      many as 84 cases were reported (incidence: 10.7%), and in the SSD group - 43
      cases (incidence: 5.2%). The odds ratio (OR) and relative risk (RR) was 2.5. The
      probability of VAP was significantly higher in the NSSD group. The risk factors
      of VAP incidence (P<0.001) included the correlation between reintubation
      (R=0.271), tracheostomy (R=0.309) and bronchoscopy (R=0.316). CONCLUSION: Use of
      endotracheal tubes with subglottic secretion drainage in patients in the ICU on
      mechanical ventilation significantly reduced the incidence of VAP.

PMID- 29042708
TI  - Analysis of the seasonal incidence of acute respiratory infections including
      influenza (ARI) in the Czech Republic - possible contribution of the functional
      data boxplot in epidemiology.
AB  - AIMS: The detection of an epidemic outbreak is possible only if the baseline
      incidence level of a given disease is well defined. The determination of the
      baseline is complicated by the presence of epidemic outbreaks in historical data.
      The aim of the paper is to provide a new way of determining the baseline.
      METHODS: The analyzed data containing weekly records on the incidence of acute
      respiratory infections including influenza (ARI) in the Czech Republic and its
      regions are taken from the nationwide surveillance system; data on 15 seasons
      from 2001/02 to 2015/16 are included. Functional boxplots of the data are
      constructed and five distinct methods (componentwise mean, componentwise median,
      median, trimmed mean, and adjusted mean) were used for the computation of the
      baseline level function. RESULTS: It was shown that the methods based on
      functional data analysis could successfully overcome the problems that arise when
      the conventional methods are used for the determination of the baseline function.
      CONCLUSION: The functional boxplot - a new statistical tool - can bring not only
      a transparent visualisation of comprehensive data, but can also help
      epidemiologists and other public health experts to determine the baseline
      incidence level of a given disease as well as to detect unusual epidemic seasons.

PMID- 29042709
TI  - Derivation and basic characterization of colorectal carcinoma primary cell lines.
AB  - BACKGROUND: Colorectal carcinoma is one of the most common malignancies in
      western countries. Among different approaches to its research, primary cancer
      cell lines can play an important role. AIM: The main purposes of this study were:
      1) to establish an effective and reproducible method of colorectal cancer cell
      isolation and cultivation from primary tumours and lymph node metastases and 2)
      to elucidate the biological features of the tumours favouring successful cell
      cultivation. MATERIALS AND METHODS: The tumour cells were obtained from colectomy
      specimens. Primary tumour and lymph node metastasis tissue was used for
      establishing the tissue cultures. Colectomy samples were further processed for
      routine histopathological assessment: tumour grade, stage, angioinvasion and
      perineural spread were evaluated. Features of tissue culture cells were assessed
      using phase contrast microscopy and immune-histochemical techniques. WST-1 assay
      and X-CELLigence real time analysis were carried out for viability and
      proliferation testing before and after treatment with irinotecan and oxaliplatin.
      Molecular features of the tumour including K-RAS/B-RAF/N-RAS mutations were
      tested using allele-specific PCR. Results of the cultivation process were
      compared to the histopathological and molecular features of the tumours. RESULTS:
      In total, we obtained 33 samples from the primary site of tumours and 20 samples
      from lymph node metastases; in total, 27 cell lines were successfully isolated.
      Morphologic features characteristic of tumour cells in primary cell lines and
      epithelial differentiation (positive for AE1/AE3 cytokeratin) were evaluated.
      Higher tumour stage, angioinvasion and presence of perineural spread in primary
      tumour correlated positively with successful cell isolation from lymph node
      metastasis. All samples tested were NRAS wild-type. No correlation was found
      between molecular phenotype and the cell culture features. A higher proliferation
      potential was observed in the primary tumour cells, whereas higher sensitivity to
      irinotecan was found in the lymph node metastatic cells. CONCLUSIONS: Using
      mechanical dissociation, we successfully derived and cultivated CRC cells from
      primary tumours and lymph node metastases with success rate 3 % and 70%
      respectively. Primary tumour features favouring successful establishment of cell
      cultures were identified.

PMID- 29042711
TI  - Shielding of Heat Transfer from a Boundary.

PMID- 29042710
TI  - Effect of sertraline in paroxysmal hypertension.
AB  - OBJECTIVE: Paroxysmal hypertension or pseudopheochromocytoma is quite a common
      problem in clinical practice. The optimal treatment for this condition has not
      been established. This study sought to investigate whether sertraline (a
      selective serotonin reuptake inhibitor) reduces the symptoms. METHODS: We
      enrolled 64 patients referred to our department between April 2008 and October
      2014 for symptomatic paroxysmal hypertension. Patients received sertraline, 50 mg
      once daily, in addition to their current medication. The effect of the treatment
      was assessed during their next clinical visit at least 3 months later. RESULTS:
      Of the 64 patients, 57 (89%) also had sustained arterial hypertension. Mean
      office baseline blood pressure (BP) was 147.6/83.8 mmHg and patients used a mean
      of 3.1 antihypertensive drugs. Five patients did not start using sertraline and
      three were lost to follow-up. Of the 56 patients who started using sertraline and
      who came for check up, clinical improvement was observed in 42 (75%) patients -
      symptoms of paroxysmal hypertension fully subsided in 28 (50%) and were partially
      reduced in 14 (25%) . Side effects or intolerance leading to discontinuation of
      treatment occurred in 7 patients (12.5%). Mean office BP in patients using
      sertraline decreased by 12.8/7.4 mmHg (P<0.001 for both). CONCLUSIONS: Sertraline
      effectively removed or reduced symptoms of paroxysmal hypertension in the
      majority of patients who used this treatment.

PMID- 29042712
TI  - Sensitivity of novel silicate and borate-based glass structures on in vitro
      bioactivity and degradation behaviour.
AB  - Three novel glass compositions, identified as NCL2 (SiO2-based), NCL4 (B2O3
      based) and NCL7 (SiO2-based), along with apatite-wollastonite (AW) were processed
      to form sintered dense pellets, and subsequently evaluated for their in vitro
      bioactive potential, resulting physico-chemical properties and degradation rate.
      Microstructural analysis showed the carbonated hydroxyapatite (HCA) precipitate
      morphology following SBF testing to be composition-dependent. AW and the NCL7
      formulation exhibited greater HCA precursor formation than the NCL2 and NCL4
      derived pellets. Moreover, the NCL4 borate-based samples showed the highest
      biodegradation rate; with silicate-derived structures displaying the lowest
      weight loss after SBF immersion. The results of this study suggested that glass
      composition has significant influence on apatite-forming ability and also
      degradation rate, indicating the possibility to customise the properties of this
      class of materials towards the bone repair and regeneration process.

PMID- 29042713
TI  - Trivial Molecules May Prevent or Hamper Tooth Decay: A Potential Voyaged?

PMID- 29042714
TI  - Challenges of Dental Care for Children with Microcephaly Carrying Zika Congenital
      Syndrome.

PMID- 29042715
TI  - Use of Temporalis Fascia Flap in the Treatment of Temporomandibular Joint
      Ankylosis: A Clinical Audit of 5 Years.
AB  - AIM: Restoration of normal function and jaw movements in patients with
      temporomandibular joint (TMJ) ankylosis has been a challenge. Various techniques
      have been provided for its treatment; but the results have been variable. The
      purpose of this paper is to present an easy and versatile method for the
      treatment of TMJ ankylosis and to decrease postoperative complications such as
      reankylosis. MATERIALS AND METHODS: This paper is a review of surgical outcome of
      interposition arthroplasty with temporalis fascia in 17 patients of unilateral
      TMJ ankylosis who underwent the above procedure. The review is based on the pre-,
      intra- and post-operative evaluation of these seventeen patients who were treated
      between 2008 and 2013. The follow-up time was 1-5 years. RESULTS: Reankylosis was
      seen in only one of the patients; the remaining patients had satisfactory mouth
      openings. CONCLUSION: Surgical treatment of TMJ ankylosis with interposition of
      temporal fascia is an effective and easy procedure for prevention for
      reankylosis. The autogeneous nature and proximity to the joint are the main
      advantages of the temporal fascia flap when compared with other interpositional
      materials.

PMID- 29042716
TI  - Effectiveness of Behavioral Vaccine on the Oral Health of Children in
      Komarapalayam, South India: A Randomized Controlled Pilot Trial.
AB  - BACKGROUND: Oral health education and promotion have emerged as a strong force
      against the traditional, dominant, and curative model of health practice. In
      pediatric dentistry, the utilization of an entertaining, easy to understand, and
      practical educational material is warranted. Behavioral vaccine is a simple,
      scientifically proven practice that is repeated to increase well-being. AIM: The
      aim of this study is to compare the effectiveness of conventional (instructional)
      dental hygiene program and "Good Behavior Game" (GBG) (contingency dental hygiene
      program - a behavioral vaccine) on the practice of oral hygiene among 5-7-year
      old schoolchildren. STUDY DESIGN: A total of sixty children aged 5-7 years were
      divided into two groups. Each group had thirty children. MATERIALS AND METHODS: A
      pretest estimation of debris index-simplified (DI-S) was carried out. Children in
      Group A were given oral health education through instructional oral hygiene
      program. Children in Group B were allowed to participate in GBG daily for a week.
      The DI-S was recorded on the 8th day and 3 months after the intervention in both
      the groups. RESULTS: In Group B, the good oral hygiene score dramatically
      increased from 10% to 93.3% 1 week after the intervention. There was a relative
      decrease in percentage of children who scored fair and poor also. At the end of 3
      month follow-up, 90% of children had good oral hygiene. In Group A, there was a
      significant improvement in oral hygiene after 1 week, but it was not significant
      after 3 months. CONCLUSION: The present study was undertaken to advance the area
      of behavioral vaccine as an alternative for teaching basic oral health concepts
      in children. In this study, the GBG was found to be an effective intervention aid
      for educating children.

PMID- 29042717
TI  - Cervical Dentin Changes in Curved Root Canals after Using WaveOne and Reciproc
      Files with Full Rotation versus Reciprocation Movement: An Ex vivo Study.
AB  - AIM: The aim of the current study was to compare the effect of WaveOne and
      Reciproc files in reciprocation versus reverse full rotation movements on
      cervical dentin thickness by virtue of cone beam computed tomography (CBCT)
      analysis in curved mesial canals of mandibular first molars. METHODS: Mesiobuccal
      canals of 60 mandibular molars were randomly divided into 4 groups (n = 15):
      Group 1; WaveOne/Reciprocation, Group 2; WaveOne/Full-Rotation, Group 3;
      Reciproc/Reciprocation, and Group 4; Reciproc/Full-Rotation. Pre- and post
      instrumented CBCT scans were prepared for assessment of cervical dentin thickness
      changes (2 mm, 4 mm below the highest point of the root furcation) in both
      groups. Data statistically analyzed using two-way ANOVA test. RESULTS: There was
      no statistically significant difference between four experimental groups in terms
      of remaining dentin thickness at 2 and 4 mm levels below the highest point of the
      furcation (P > 0.05). No separation of instruments occurred in any group.
      CONCLUSION: WaveOne and Reciproc files with two different motions have similar
      effects on cervical of root canals in terms of dentin thickness changes.

PMID- 29042718
TI  - Are Local Anesthesia Vials Similar to Champagne: Do they Lose their Potency Once
      Opened?: An In vitro study.
AB  - BACKGROUND AND OBJECTIVES: Epinephrine is volatile and unstable on exposure to
      air. Addition of sodium metabisulfite as an antioxidant has been effective, but
      there are no clear-cut consensus on its efficiency in retarding the oxidation
      that sets in once the anesthetic vials are kept open with a needle in situ. There
      is a paucity of scientific data regarding the risks of reuse of anesthetic vials
      following the use of cartridges, a common practice in western countries. It is
      our endeavor to shed light on the constant change in pH, drug deterioration, and
      instability that sets in an anesthetic vial with a needle in situ. METHODS:
      Twenty sets of identical local anesthetic vials (lidocaine 2% with 1:80,000
      adrenaline) were collected. The samples were divided into four individual groups
      followed by a segregation of 5 subsamples at varying time intervals from each
      individual group. pH was measured using pH meter. RESULTS: Change in the pH of
      the solution was noted as days progressed in open local anesthetic vials when
      compared to closed vials. However, the decreased pH remained constant following a
      brief time interval after complete conversion of sulfite to sulfate. CONCLUSIONS:
      Local anesthetic vials with needle pricked in for a longer duration can alter the
      pH, concentration of the vasoconstrictor and deteriorate the properties of local
      anesthetic solution. This can manifest clinically as delayed onset of action,
      increased burning sensation, and pain on administration.

PMID- 29042719
TI  - A Novel Conservative Approach Combining "SealBio" and "Surgical Fenestration" for
      Healing of Large Periapical Cystic Lesions of Endodontic Origin: A Pilot Study.
AB  - OBJECTIVES: To evaluate the treatment outcome of large periapical cystic lesions
      treated by combining two novel, conservative approaches, "SealBio" and "Surgical
      Fenestration". MATERIALS AND METHODS: Five cases (4M:1F, age range 14-38 years,
      mean age 24.5 years) of large periapical cystic lesions, diagnosed on clinical
      and radiographic examination, were included in the study. After informed consent,
      endodontic treatment was initiated; chemo-mechanical preparation and intra-canal
      dressing of calcium hydroxide was given. At the next sitting after one week,
      further disinfection root canals was done by "apical clearing", "apical foramen
      widening" and irrigation. A cotton pellet was kept in the access cavity. After
      local anaesthesia, full thickness muco-periosteal flap was reflected and the
      thinned out bone was removed with bone rongers, a small piece of cystic lining
      was excised and the cystic cavity was copiously flushed with Betadine solution.
      The remaining cystic lining was gently curetted and the flap was sutured back.
      "SealBio" was performed after gentle irrigation with saline and intentional over
      instrumentation. A calcium sulphate based cement was pushed in the cervical third
      of the canal and the access opening was sealed with glass ionomer cement. Patient
      was prescribed antibiotics and anti-inflammatory drugs for 5 days and sutures
      were removed after 7 days. Patients were followed up clinically and
      radiographically at regular intervals. CONCLUSIONS: In this pilot study,
      treatment outcome after combined technique of "SealBio" and "Surgical
      fenestration" was found to be highly effective in healing of large periapical
      cystic lesions. It was simple to perform and very conservative treatment; it
      required minimal bone removal, obviated the need for complete cyst enucleation,
      apicectomy and retrograde filling.

PMID- 29042720
TI  - Microtensile Bond Strength and Failure Modes of Flowable Composites on Primary
      Dentin with Application of Different Adhesive Strategies.
AB  - BACKGROUND: Resin composite is an option for the restoration of primary teeth,
      and new materials with simplified procedures are increasingly being suggested.
      AIMS: This study aims to evaluate the microtensile bond strengths and fracture
      modes of flowable composites on primary dentin with application of different
      adhesive strategies. MATERIALS AND METHODS: Sixty extracted noncaries primary
      molars were abraded from buccal surfaces to expose dentin surface. The teeth were
      randomly divided into three groups as follows: Group 1, VertiseTM Flow (Kerr)
      (self-adhering flowable composite); Group 2, G-aenial Universal Flo(r) (GC
      Europe) (used with one-step self-etch system); Group 3, Tetric(r) N-Flow
      (Ivoclar/Vivadent) (used with two-step total etch system). Then, the flowable
      composites were applied to buccal dentin surfaces with the help of guide mold.
      Samples were embedded in acrylic blocks and sectioned to form dentin-composite
      sticks with a surface area of approximately 1 mm2. Finally, a total of 180 sticks
      were obtained to give each group of 60 sticks. Microtensile bond strengths were
      measured using a universal testing machine (1 mm/min). Fracture modes were
      evaluated with scanning electron microscopy. STATISTICAL ANALYSIS: Microtensile
      bond strengths data were analyzed by Kruskal-Wallis nonparametric test. RESULTS:
      The microtensile bond strengths of G-aenial (15.5 megapascals [Mpa]) and Tetric
      (13.0 MPa) were statistically significant higher than Vertise (2.3 MPa). It was
      recorded that most of fractures in G-aenial was 40% cohesive, Tetric was 53.3%
      mixed, and Vertise was 83.3% adhesive. CONCLUSIONS: The self-adhering flowable
      composite VertiseTM Flow had the lowest and G-aenial Universal Flo(r) had the
      highest microtensile bond values.

PMID- 29042721
TI  - Clinical and Radiographic Evaluation of Citric Acid-Based Nano Hydroxyapatite
      Composite Graft in the Regeneration of Intrabony Defects - A Randomized
      Controlled Trial.
AB  - BACKGROUND: Conventional periodontal therapy with various bone grafts has limited
      scope and the results are not predictable. To improve their utility, the
      hybridization of bioceramics and biodegradable polymers has been widely adopted
      to reform the mechanical properties of bone grafts. One such biodegradable
      polymer is POC (Poly 1,8 octanediol). Secondly, citric acid is considered as the
      key material in bone mineralization, which is related to the overall stability,
      strength and fracture resistance of bone. Hence citric acid is incorporated in a
      polymer and Nano hydroxyapatite to form a composite graft, for periodontal bone
      regeneration. This study attempts to evaluate the efficacy of citric acid based
      Nano-hydroxyapatite composite graft for the treatment of intrabony defects in
      chronic periodontitis patients over 12 months. METHODS: A split mouth study,
      which consists of 10 systemically healthy patients, were randomly treated with
      Citric acid based Nano hydroxyapatite composite graft (test sites, n=18) or with
      Nano hydroxyapatite alone (control sites, n=15). Plaque index, gingival index,
      gingival bleeding index, probing pocket depth (PPD), clinical attachment level
      (CAL), bone probing depth (BPD) and hard tissue parameters such as amount of
      defect fill, percentage of defect fill, and changes in alveolar crest were
      assessed over a period of 12 months. Statistical analysis used was student's t
      test and One-Way ANOVA. RESULTS: Both test and control sites demonstrated
      statistically significant reduction of PD, BPD, gain in CAL and radiographic bone
      fill. Nevertheless the test sites showed Statistically significant improvements
      in all the parameters as compared to control sites at 12 months. CONCLUSION:
      Citric acid based Nano hydroxyapatite composite graft can be considered as a
      newer material for periodontal regeneration.

PMID- 29042722
TI  - Salutogenesis: A New Approach toward Oral Health Promotion.
AB  - INTRODUCTION: Sense of coherence (SOC) is hypothesized to be an important
      psychological factor that enables people to cope with stressors and successfully
      maintain and improve health. Very few publications report on the relationship
      between "salutogenesis," as measured by the concept of SOC and oral health
      status. However, little is known about the relationship between the mother's SOC
      and dental caries of their children. AIMS AND OBJECTIVES: The aim of the present
      study was to explore the impact of mother's SOC level on dental caries status of
      their children. MATERIALS AND METHODS: A school-based cross-sectional study was
      conducted with the children aged 4-8 years attending public school (n = 200).
      Questionnaires were applied to mothers to obtain level of SOC. Dental caries
      status in children was assessed using decayed, missing, filled tooth surfaces
      (DMFS) and/or dmfs index. One-way analysis of variance F-test and post hoc Tukey
      test were used to assess the effect of mother's SOC level on their children's
      caries dmfs index. RESULTS: Mean of dmfs and/or DMFS in children showed
      statistically significant relation with their mother's SOC level (P < 0.01). On
      intergroup comparison, significant (P < 0.01) difference was found when mean of
      dmfs and/or DMFS with mothers having low SOC and high SOC was compared. However,
      there was no significant relation when mean was compared to mothers with medium
      and low SOC. CONCLUSION: Dental caries of children gets influenced by mother's
      SOC level. There was an inverse relationship between mother's SOC level and their
      children dental caries status.

PMID- 29042723
TI  - Effect of Different Irrigating Solutions on Depth of Penetration of Sealer into
      Dentinal Tubules: A Confocal Microscopic Study.
AB  - AIM: The aim of the study was to evaluate the effect of different irrigating
      solutions used in final irrigation on depth of sealer penetration into dentinal
      tubules. MATERIALS AND METHODS: Thirty recently extracted, human mandibular
      premolar teeth with single canals were randomly divided into two groups, and one
      of the two irrigants was used in each group - Group A (Chitosan) and Group B
      (Ethylenediaminetetraacetic acid). All the teeth were obturated with gutta-percha
      and AH 26(r) sealer labeled with fluorescent dye. The teeth were sectioned at
      distances 2, 5, and 8 mm from the root apex. Maximum depth of sealer penetration
      was measured using confocal laser scanning microscopy. STATISTICAL ANALYSIS:
      Statistical analysis used One-way analysis of variance and t-test. RESULTS: At
      coronal third depth, the sealer penetration was greater in
      ethylenediaminetetraacetic acid (EDTA) group; however, depth of sealer
      penetration was greater at apical third in chitosan group. CONCLUSION: Final
      irrigation with EDTA and chitosan after the use of sodium hypochlorite affected
      sealer penetration.

PMID- 29042724
TI  - Evaluation of Bond Strength between Grooved Titanium Alloy Implant Abutments and
      Provisional Veneering Materials after Surface Treatment of the Abutments: An In
      vitro Study.
AB  - INTRODUCTION: Titanium has become the material of choice with greater
      applications in dental implants. The success of the dental implant does not only
      depend on the integration of the implant to the bone but also on the function and
      longevity of the superstructure. The clinical condition that demands long-term
      interim prosthesis is challenging owing to the decreased bond between the
      abutment and the veneering material. Hence, various surface treatments are done
      on the abutments to increase the bond strength. AIM: This study aimed to evaluate
      the bond strength between the abutment and the provisional veneering materials by
      surface treatments such as acid etching, laser etching, and sand blasting of the
      abutment. MATERIALS AND METHODS: Forty titanium alloy abutments of 3 mm diameter
      and 11 mm height were grouped into four groups with ten samples. Groups A, B, C,
      and D are untreated abutments, sand blasted with 110 MUm aluminum particles,
      etched with 1% hydrofluoric acid and 30% nitric acid, and laser etched with Nd:
      YAG laser, respectively. Provisional crowns were fabricated with bis-acrylic
      resin and cemented with noneugenol temporary luting cement. The shear bond
      strength was measured in universal testing machine using modified Shell-Nielsen
      shear test after the cemented samples were stored in water at 25 degrees C for 24
      h. Load was applied at a constant cross head speed of 5 mm/min until a sudden
      decrease in resistance indicative of bond failure was observed. The corresponding
      force values were recorded, and statistical analysis was done using one-way ANOVA
      and Newman-Keuls post hoc test. RESULTS: The laser-etched samples showed higher
      bond strength. CONCLUSION: Among the three surface treatments, laser etching
      showed the highest bond strength between titanium alloy implant abutment and
      provisional restorations. The sand-blasted surfaces demonstrated a significant
      difference in bond strength compared to laser-etched surfaces. The results of
      this study confirmed that a combination of surface treatments and bond agents
      enhances the bond strength.

PMID- 29042725
TI  - The Effect of Polymerization and Preparation Techniques on the Microleakage of
      Composite Laminate Veneers.
AB  - BACKGROUND: Marginal leakage is the important factor influencing the maintenance
      of dental esthetic. AIM: The purpose of this study was to evaluate the
      relationship between the preparation techniques and type of polymerization
      techniques on microleakage of composite laminate veneers. MATERIALS AND METHODS:
      Ninety-one same sized, caries-free human maxillary central incisors were randomly
      assigned to 13 groups (n = 7) and were designed with four different preparation
      techniques (window type, feather type, bevel type, and incisal overlap type). One
      group determined as control group and any preparation was applied. Nanohybrid
      resin composite was used for restoration. Composite laminate veneers polymerized
      with three different techniques (direct light curing, indirect polymerization
      with a combination of pressure, light and heat using a light cup and heat cup,
      direct polymerization, and additionally heat cured in an oven). The specimens
      were thermocycled, and then immersed in 5% basic fuchsine solution. Following 24
      h, all specimens were immersed in 65% nitric acid solutions for volumetric dye
      extraction test. Samples diluted with distilled water and centrifuged and
      microleakage determined by a spectrophotometer. STATISTICAL ANALYSIS USED: Data
      were analyzed with two-way ANOVA and Tukey honest significant difference post hoc
      multiple comparisons test (P < 0.05). RESULTS: For comparing the microleakage
      value of preparation and polymerization techniques, Window type preparation
      showed a significant difference in direct polymerization + additional cured group
      (P < 0.05). Control group was statistically different from the other groups (P <
      0.05). CONCLUSIONS: Window type laminate preparation can be preferred in indirect
      polymerization technique because it caused less leakage in this present study.

PMID- 29042726
TI  - Comparative Evaluation of Conventional and Accelerated Castings on Marginal Fit
      and Surface Roughness.
AB  - AIMS: The aim of this study was to evaluate the marginal fit and surface
      roughness of complete cast crowns made by a conventional and an accelerated
      casting technique. SETTINGS AND DESIGN: This study was divided into three parts.
      In Part I, the marginal fit of full metal crowns made by both casting techniques
      in the vertical direction was checked, in Part II, the fit of sectional metal
      crowns in the horizontal direction made by both casting techniques was checked,
      and in Part III, the surface roughness of disc-shaped metal plate specimens made
      by both casting techniques was checked. MATERIALS AND METHODS: A conventional
      technique was compared with an accelerated technique. In Part I of the study, the
      marginal fit of the full metal crowns as well as in Part II, the horizontal fit
      of sectional metal crowns made by both casting techniques was determined, and in
      Part III, the surface roughness of castings made with the same techniques was
      compared. STATISTICAL ANALYSIS USED: The results of the t-test and independent
      sample test do not indicate statistically significant differences in the marginal
      discrepancy detected between the two casting techniques. RESULTS: For the
      marginal discrepancy and surface roughness, crowns fabricated with the
      accelerated technique were significantly different from those fabricated with the
      conventional technique. CONCLUSIONS: Accelerated casting technique showed quite
      satisfactory results, but the conventional technique was superior in terms of
      marginal fit and surface roughness.

PMID- 29042727
TI  - Clinical and Radiographic Evaluation of Procedural Errors during Preparation of
      Curved Root Canals with Hand and Rotary Instruments: A Randomized Clinical Study.
AB  - BACKGROUND: The process of cleaning and shaping the canal is not an easy goal to
      obtain, as canal curvature played a significant role during the instrumentation
      of the curved canals. AIM: The present in vivo study was conducted to evaluate
      procedural errors during the preparation of curved root canals using hand
      Nitiflex and rotary K3XF instruments. MATERIALS AND METHODS: Procedural errors
      such as ledge formation, instrument separation, and perforation (apical, furcal,
      strip) were determined in sixty patients, divided into two groups. In Group I,
      thirty teeth in thirty patients were prepared using hand Nitiflex system, and in
      Group II, thirty teeth in thirty patients were prepared using K3XF rotary system.
      The evaluation was done clinically as well as radiographically. The results
      recorded from both groups were compiled and put to statistical analysis.
      STATISTICAL ANALYSIS: Chi-square test was used to compare the procedural errors
      (instrument separation, ledge formation, and perforation). RESULTS: In the
      present study, both hand Nitiflex and rotary K3XF showed ledge formation and
      instrument separation. Although ledge formation and instrument separation by
      rotary K3XF file system was less as compared to hand Nitiflex. No perforation was
      seen in both the instrument groups. CONCLUSION: Canal curvature played a
      significant role during the instrumentation of the curved canals. Procedural
      errors such as ledge formation and instrument separation by rotary K3XF file
      system were less as compared to hand Nitiflex.

PMID- 29042728
TI  - One-stage Full Mouth Disinfection Using 20% Propolis Hydroalcoholic Solution: A
      Clinico-microbiologic Study.
AB  - BACKGROUND: Propolis is a resinous substance produced by honeybees which has many
      therapeutic properties because of its unique composition. It has been widely used
      since many years for different medicinal purposes. AIM: The aim of this study was
      to investigate the effects of one-stage full mouth disinfection (OSFMD) using 20%
      propolis hydroalcoholic solution in chronic periodontitis patients. MATERIALS AND
      METHODS: Thirty patients diagnosed with chronic periodontitis and presenting
      three or more nonadjacent teeth with deep pockets were selected for the study.
      Clinical parameters including gingival index, plaque index, bleeding on probing,
      probing pocket depth, and clinical attachment level were recorded at baseline in
      all the patients followed by subgingival plaque sampling. All the thirty patients
      were randomly allocated into two groups; 15 patients (control group) were
      subjected to scaling and root planning (SRP) alone, and in remaining 15 patients
      (test group), SRP was done followed by OSFMD using 20% propolis hydroalcoholic
      solution after 24 h. All the patients were kept at periodic recall, and clinical
      and microbiological parameters were again taken at 4 weeks and 12 weeks. RESULTS:
      There was a significant improvement for all the clinical parameters, with higher
      probing depth reduction and attachment gain in the test group when compared to
      the control group. Furthermore, the microbiological counts of the
      periodontopathogens were found to decrease considerably more in the test group.
      CONCLUSION: SRP followed by OSFMD with propolis extract after 24 h was more
      effective than SRP alone in chronic periodontitis patients.

PMID- 29042729
TI  - Attitudes of Parents and Children toward Primary Molars Restoration with
      Stainless Steel Crown.
AB  - CONTEXT: Today, attention has increasingly been focused on the studies which
      include patient-centered consequences. AIMS: The study aims to investigate the
      attitude of parents and children toward the application of stainless steel crown
      (SSC) on primary molars. SETTINGS AND DESIGN: This cross-sectional descriptive
      study included eighty 4-6-year-old children having treated with SSC over the past
      3-6 months. SUBJECTS AND METHODS: Eventually, a validated child- and parent
      centered self-report questionnaire was filled, having 14 questions about
      demographic information, six questions about childrens' attitude, and eight
      questions about parents' attitude. STATISTICAL ANALYSIS USED: Data analysis was
      conducted using t-test and one-way ANOVA at significant level P < 0.05. RESULTS:
      In general, the score of children's attitude was positive, and the mean of
      attitude scores was obtained to be 9.9 +/- 2.6; attitudes of 82.43% of children
      were good. Parents had neutral attitude; the mean of their attitude was obtained
      to be 20.2 +/- 4.8. Only 53% of the parents scored good attitudes. CONCLUSIONS:
      The attitude score of children toward SSC was good and independent of age,
      gender, career, and education of the parents. Although the parents were not
      satisfied with how it appeared, the majority of them reported that their child
      had well accepted the crown.

PMID- 29042730
TI  - A Comparative Scanning Electron Microscopic Analysis of the Effect of QMix(r) and
      SofScaleTM as an Adjunct to Scaling and Root Planing on Periodontally Compromised
      Root Surfaces: An In vitro Study.
AB  - AIM: This study aimed to comparatively analyze, under scanning electron
      microscope (SEM), the effect of the use of QMix(r) and SofScaleTM as an adjunct
      to scaling and root planing (SRP) on periodontally compromised root surfaces.
      SETTINGS AND DESIGN: This study was carried out in K. M. Shah Dental College and
      Hospital, Vadodara. METHODOLOGY: This was a single-blinded in vitro study which
      compared QMix(r) and SofScaleTM as an adjunct to SRP on periodontally compromised
      root surfaces under SEM. STATISTICAL ANALYSIS USED: Statistical analysis was done
      using a nonparametric Mann-Whitney U-test to test the null hypothesis that there
      is no difference between the test and control groups. RESULTS: The sum of ranks
      for QMix(r) was 306.50 and the sum of ranks for SofScaleTM was 513.50. The group
      which was treated with QMix(r) showed statistically significant results (P =
      0.004) as compared to group which was treated with SofScaleTM. CONCLUSION:
      Comparative analysis showed that QMix(r) had significantly better smear layer
      removal ability as compared to SofScaleTM. However, uniform root surface was
      achieved with both QMix(r) and SofScaleTM.

PMID- 29042731
TI  - Dimensional Evaluation of Root Resorption Areas in Differing Severity of Chronic
      Periodontitis: A Scanning Electron Microscopic Study.
AB  - AIM: The aim of this study was to evaluate root surface alterations in terms of
      location, length, and depth of root resorption in the gingival, middle, and
      apical third of the mesial and distal surfaces of the root in healthy and
      periodontally affected teeth with chronic periodontitis. MATERIALS AND METHODS:
      Teeth diagnosed with differing severity of chronic periodontitis, as assessed by
      clinical and radiographic parameters of bone destruction, were observed under a
      scanning electron microscope. Existence and location of root resorption areas, as
      well as length and depth of the resorption on each radicular third of the teeth,
      were determined. RESULTS: Totally 27 teeth (60%) among all the groups exhibited
      root resorption. The number of teeth showing root resorption in each group was
      divided into the following groups; Group I: 2 teeth (13.33%); Group II: 11 teeth
      (73.33%); and Group III: 14 teeth (93.33%). The most affected teeth were the
      mandibular incisors. The apical one-third of the root was the most affected and
      the gingival third of the root was the least affected with respect to the length
      and depth of the root resorption. The mesial surface of the root was more
      commonly affected when compared to the distal surface of the root. CONCLUSION: It
      may thus be concluded that the existence and extent of root resorption depend on
      the severity of periodontal destruction.

PMID- 29042732
TI  - Comparative Evaluation of Cone-beam Computed Tomography versus Direct Surgical
      Measurements in the Diagnosis of Mandibular Molar Furcation Involvement.
AB  - AIM: Periodontists frequently experience inconvenience in accurate assessment and
      treatment of furcation areas affected by periodontal disease. Furcation
      involvement (FI) most commonly affects the mandibular molars. Diagnosis of
      furcation-involved teeth is mainly by the assessment of probing pocket depth,
      clinical attachment level, furcation entrance probing, and intraoral periapical
      radiographs. Three-dimensional imaging has provided advantage to the clinician in
      assessment of bone morphology. Thus, the present study aimed to compare the
      diagnostic efficacy of cone-beam computed tomography (CBCT) as against direct
      intrasurgical measurements of furcation defects in mandibular molars. SUBJECTS
      AND METHODS: Study population included 14 patients with 25 mandibular molar
      furcation sites. CBCT was performed to measure height, width, and depth of
      furcation defects of mandibular molars with Grade II and Grade III FI.
      Intrasurgical measurements of the FI were assessed during periodontal flap
      surgery in indicated teeth which were compared with CBCT measurements.
      Statistical analysis was done using paired t-test and Bland-Altman plot. RESULTS:
      The CBCT versus intrasurgical furcation measurements were 2.18 +/- 0.86 mm and
      2.30 +/- 0.89 mm for furcation height, 1.87 +/- 0.52 mm and 1.84 +/- 0.49 mm for
      furcation width, and 3.81 +/- 1.37 mm and 4.05 +/- 1.49 mm for furcation depth,
      respectively. Results showed that there was no statistical significance between
      the measured parameters, indicating that the two methods were statistically
      similar. CONCLUSION: Accuracy of assessment of mandibular molar FI by CBCT was
      comparable to that of direct surgical measurements. These findings indicate that
      CBCT is an excellent adjunctive diagnostic tool in periodontal treatment
      planning.

PMID- 29042733
TI  - Effect of Melaleuca alternifolia Mixed with Tissue Conditioners in Varying Doses
      on Colonization and Inhibition of Candida albicans: An In Vitro Study.
AB  - AIMS AND OBJECTIVES: The study was conducted to evaluate the Colonization &
      Inhibition of Candida albicans in selected commercially available denture lining
      materials material by mixing them with varying concentrations and doses of tea
      tree oil. MATERIALS AND METHODS: Five test discs of 10mm diameter and 1.5mm
      thickness were prepared using commercially available soft denture lining
      materials (Viscogel and GC-soft). Tea tree oil of varying concentrations (10%,
      20%, 30%, and 40%) and doses (0.5 ml, 1.0 ml, 1.5 ml, 2.0 ml) were added during
      manipulation. Test discs kept in sterile artificial saliva were inoculated with
      Candida albicans (ATCC-2091 strain) and incubated for 6 weeks. These discs were
      fixed, dehydrated air dried and stained using 0.03% acridine orange stain and
      observed under Fluorescent microscope to count the colonies on the surface of
      each disc to evaluate the colonization. To evaluate inhibition, test discs were
      placed on the top of Sabouraud's dextrose agar inoculated with Candida albicans
      (ATCC-2091 strain). After incubation at 370C for 48 hours, the zone of Inhibition
      formed around the samples was measured. RESULTS: The GC soft liner had higher
      mean colonization and lesser zone of inhibition of C.albicans when compared to
      Visco-gel soft liner (P < 0.001) and highest zone of inhibition observed with 2
      ml volume and 40% vol/vol concentration of melaleuca alternifolia (P < 0.05).
      INTERPRETATION AND CONCLUSION: By the addition of Tea Tree oil, Viscogel had good
      acquired good antifungal properties than GC-soft lining materials.

PMID- 29042734
TI  - Influence of Bleaching Regimen and Time Elapsed on Microtensile Bond Strength of
      Resin Composite to Enamel.
AB  - OBJECTIVES: The aim of this study was to evaluate the effects of time elapsed
      since bleaching and different bleaching regimens on the microtensile bond
      strength of resin composite to enamel. METHODOLOGY: Forty flattened buccal enamel
      surfaces were divided into four groups: An unbleached (control) group and three
      bleaching groups. Control group specimens were not subjected to a bleaching
      regimen (Group 1), while those in the bleaching groups were bleached as follows:
      opalescence 10% (Group 2), whiteness perfect 16% (Group 3), and whiteness
      hydrogen peroxide 35% (Group 4). Thereafter, the bleached specimens were divided
      into three subgroups (n = 4 teeth each) for restoration according to
      predetermined posttreatment time intervals (immediately, 1 week, and 2 weeks).
      Bonded specimens were then sectioned and subjected to MUTBS testing. The data
      were analyzed using Kruskal-Wallis and Mann-Whitney U-tests at alpha = 0.05.
      RESULTS: There was a significant difference in the MUTBS of the resin composite
      to enamel in groups that were bonded immediately after bleaching and in the
      control group (P < 0.05). Compared to the control group, the MUTBS in Groups 2,
      3, and 4 decreased significantly 1-week postbleaching (P < 0.05). No significant
      difference in MUTBS was observed between the bleached and unbleached groups 2
      weeks after treatment (P > 0.05). CONCLUSIONS: Adhesive restorative procedures
      could not be performed immediately or after 1 week irrespective of the type or
      concentration of bleaching system used. Composite restorations on bleached enamel
      surfaces should be performed after an interval of at least 2 weeks.

PMID- 29042735
TI  - Effectiveness of Three Different Irrigants - 17% Ethylenediaminetetraacetic Acid,
      Q-MIX, and Phytic Acid in Smear Layer Removal: A Comparative Scanning Electron
      Microscope Study.
AB  - BACKGROUND: Removal of smear layer from the root canal walls is important for
      long-standing endodontic success. AIM: The aim of this study is to evaluate and
      compare smear layer removing ability among 17% ethylenediaminetetraacetic acid
      (EDTA), Q-MIX, and phytic acid by scanning electron microscopy (SEM). MATERIALS
      AND METHODS: This in-vitro experimental study assessed smear layer removal using
      three different irrigants. Thirty single-rooted freshly extracted human permanent
      premolars were collected, disinfected, and decoronated to a standardized root
      length of 13 mm. Root canals were cleaned and shaped till F2 universal rotary
      protaper at working length 1 mm short of the apex. They were randomly divided
      into three groups, and final irrigation was done accordingly. Group 1 (n = 10):
      with 1 ml of 17% EDTA, Group 2 (n = 10): with 1 ml of Q-MIX, Group 3 (n = 10):
      with 1 ml of phytic acid. Samples were then longitudinally sectioned and
      evaluated under SEM at coronal, middle, and apical levels. STATISTICAL ANALYSIS:
      Two-way analysis of variance and Tukey's post hoc test were performed. The level
      of significance was set at 0.05. RESULTS: Smear layer removing ability among
      irrigants and sections in descending order: 17 EDTA > Q-MIX > phytic acid;
      coronal > middle > apical. CONCLUSION: 17% EDTA showed better and promising
      results followed by Q-MIX and then phytic acid.

PMID- 29042736
TI  - Multiple Gingival Recession Coverage Treated with Vestibular Incision
      Subperiosteal Tunnel Access Approach with or without Platelet-Rich Fibrin - A
      Case Series.
AB  - BACKGROUND: Gingival recession involves both soft tissue and hard tissue loss. In
      this evolutionary era of dentistry, newer techniques have evolved for complete
      coverage of isolated recession defects. Since 2012, vestibular incision
      subperiosteal tunnel access (VISTA) technique was used with various regenerative
      membranes to treat multiple recession defects (MRDs). Platelet-rich fibrin (PRF)
      membrane, a pool of growth factors but have any added advantage to recession
      coverage techniques is controversial. Thus, in this case series, we compare the
      effect of VISTA with or without PRF-membrane for the treatment of Classes I and
      III MRDs. SUBJECTS AND METHODS: Four patients between of age 30 and 40 years (two
      patients having bilateral Class I and another two having bilateral Class III
      MRDs) were selected from the Department of Periodontics, ITS Dental College,
      Greater Noida and designated as Case I-IV simultaneously. Recession defects at
      antagonist sites in each patient were corrected by VISTA approach with or without
      PRF-membrane. Recorded clinical parameters included recession depth, recession
      width, pocket probing depth, and clinical attachment level (CAL) at baseline and
      6 months postoperatively. RESULTS: Patients having Class I recession defects
      showed almost complete root coverage with VISTA technique alone and reflected no
      added advantage of PRF-membrane. However, patients with Class III recession
      defects treated with VISTA + PRF-membrane showed more reduction in recession
      depth and gain in CAL as compared to sites treated with VISTA only. CONCLUSION:
      VISTA alone is a convenient technique for treatment of Class I MRDs. Addition of
      PRF-membrane for Class III recession defects give better outcome in term of
      reduction of recession depth and gain in CAL 6 month postoperatively.

PMID- 29042737
TI  - Nance-Horan Syndrome: A Rare Case Report.
AB  - Dentofacial anomalies may guide us to the diagnosis of many congenital and
      hereditary syndromes. A 9-year-old boy was diagnosed with Nance-Horan syndrome.
      This syndrome is an extremely rare X-linked genetic disorder which is entirely
      expressed in males with semi-dominant transmission which results from mutations
      occurring in male gametes. It is characterized by facial dysmorphism such as long
      face, prominent nose and mandibular prognathism, ocular abnormalities such as
      congenital cataract, microcornea, microphthalmia and strabismus, and dental
      anomalies including mulberry molars and screwdriver-shaped incisors. Heterozygous
      females inherit this disease and also suffer from this syndrome but in a milder
      form. Approximately one-third of the affected males show signs of developmental
      delay and intellectual abnormalities. This syndrome is very rare and the
      incidence of the disease has not been established so far. The present article
      describes the clinical and radiological features and the genetic implications of
      this syndrome.

PMID- 29042738
TI  - Prosthetic Rehabilitation of Mandibular Defects with Fixed-removable Partial
      Denture Prosthesis Using Precision Attachment: A Twin Case Report.
AB  - The restoration of normal function and esthetic appearance with a dental
      prosthesis is a major challenge in the rehabilitation of patients who have lost
      their teeth and surrounding bone because of surgery for oral cyst or tumor.
      Rehabilitation with fixed or removable prosthesis is even more challenging when
      the edentulous span is long and the ridge is defective. Anatomic deformities and
      unfavorable biomechanics encountered in the region of resection add to the
      misery. In such situation, a fixed-removable prosthesis allows favorable
      biomechanical stress distribution along with restoration of esthetics, phonetics,
      comfort, hygiene, and better postoperative care and maintenance. This article
      describes rehabilitation of two cases with mandibular defects with an attachment
      retained fixed-removable hybrid prosthesis.

PMID- 29042739
TI  - Robinow Syndrome and Fusion of Primary Teeth.
AB  - Managing patients with rare genetic disorders is a challenge that dentists face
      often. Robinow syndrome (RS) is one such rare genetic disorder with <200 cases
      reported worldwide. RS demonstrates multiple craniofacial abnormalities and
      orodental disorders, which need to be taken into consideration by a dental
      practitioner while rendering dental care.

PMID- 29042740
TI  - Arteriovenous Malformation of Face.
AB  - Arteriovenous malformations (AVMs) are rare congenital vascular malformations
      accounting only 1.5% of all vascular anomalies with 50% occurrence in the oral
      and maxillofacial region. It usually results from birth defects of the
      vasculature. A literature search revealed only few case reports of AVMs in the
      facial region. Lack of meticulous diagnosis, scarcity of knowledge, and paucity
      of literature can result in their exsanguinations leading to fatal hemorrhagic
      incidents after various dental procedures such as tooth extraction, surgical
      intervention, puncture wound, or blunt injury in involved area. The present case
      describes the accidental diagnosis of asymptomatic high-flow AVMs in the facial
      region of pediatric patient reported primarily for the treatment of periapical
      abscess. This case report is unique because although there was no history of
      bleeding episodes, thorough examination and investigations diagnosed it as high
      flow vascular malformation. It is important for the dental practitioner to be
      aware of AVM which may be present in the head and neck region that can produce
      fatal bleeding episodes during various dental procedures. Proper diagnosis of
      AVMs through complete history, precise clinical examination, and advanced imaging
      modalities can help in preventing serious life-threatening complications.

PMID- 29042741
TI  - Management of Broken Dental Implant Abutment in a Patient with Bruxism: A Rare
      Case Report and Review of Literature.
AB  - This rare case report describes prosthodontic complications resulting from a
      dental implant was placed surgically more distally in the area of the missing
      mandibular first molar with a cantilever effect and a crest width of >12 mm in a
      59-year-old patient who had a history of bruxism. Fracture of abutment is a
      common complication in implant was placed in area with high occlusal forces.
      Inability to remove the broken abutment may most often end up in discarding the
      implant. Adding one more dental implant mesially to the previously placed
      implant, improvisation of technique to remove the broken abutment without
      sacrificing the osseointegrated dental implant, fabrication with cemented custom
      made abutment to replace the broken abutment for the first implant, and the use
      of the two implants to replace a single molar restoration proved reliable and
      logical treatment solutions to avoid these prosthodontic complications.

PMID- 29042742
TI  - Class II Young Adult Treatment with Twin Force Bite Corrector: 10-Year Follow-up.
AB  - One of the most preferred compliance free fixed functional appliances in
      nongrowing patients is Twin Force Bite corrector (TFBC). The aim of this case
      report is to evaluate the effectiveness of TFBC in the treatment of an adult
      Class II case. A 16-year 1-month-old boy having skeletal and dental Class II
      relationship was selected. Roth 0.018 * 0.025 inch slots brackets were attached;
      a fixed lingual arch in the mandibular dental arch and a Nance appliance in the
      maxillary dental arch were used to increase anchorage. The TFBC therapy used for
      sagittal activation and stimulation of forward mandibular growth lasted for 3
      months. The post-TFBC treatment lasted 6 months and the total treatment time was
      9 months. Treatment of a young adult Class II malocclusion with TFBC resulted in
      a Class I molar occlusion, an ideal overjet, overbite, and incisor angulation in
      a short time and maintained in the 10-year follow-up.

PMID- 29042743
TI  - Necrotizing Ulcerative Gingivitis.
AB  - Necrotizing ulcerative gingivitis (NUG) is a typical form of periodontal
      diseases. It has an acute clinical presentation with the distinctive
      characteristics of rapid onset of interdental gingival necrosis, gingival pain,
      bleeding, and halitosis. Systemic symptoms such as lymphadenopathy and malaise
      could be also found. There are various predisposing factors such as stress,
      nutritional deficiencies, and immune system dysfunctions, especially, HIV
      infection that seems to play a major role in the pathogenesis of NUG. The
      treatment of NUG is organized in successive stages: first, the treatment of the
      acute phase that should be provided immediately to stop disease progression and
      to control patient's feeling of discomfort and pain; second, the treatment of the
      preexisting condition such as chronic gingivitis; then, the surgical correction
      of the disease sequelae like craters. Moreover, finally, maintenance phase that
      allows stable outcomes. This case report describes the diagnosis approach and the
      conservative management with a good outcome of NUG in a 21-year-old male patient
      with no systemic disease and probable mechanism of pathogenesis of two
      predisposing factors involved.

PMID- 29042744
TI  - Palatal Perforation: A Rare Complication of Postanesthetic Necrosis.
AB  - The everyday practice of dentistry relies heavily on achieving adequate local
      anesthesia. Even though the safety record of local anesthetic agents is high,
      complications do occur. Palate is a favorable site for soft-tissue lesions.
      Various factors such as direct effects of the drug, blanching of the tissues
      during injection, relatively poor blood supply, and reactivation of the latent
      forms of herpes can all promote to tissue ischemia and a lesion in the palate.
      Among various complications, anesthetic necrotic ulcer is a rare and uncommon
      condition occurring mostly in the hard palate possibly after a local anesthetic
      infiltration. The ulceration is often deep and shows spontaneous but delayed
      healing. If proper treatment is not instituted on time, the necrosis can reach
      deep into the bone causing sequestrum formation and ultimately leading to palatal
      perforation. Here, we report a case of palatal perforation in a male patient
      followed by surgical interventions and follow-up.

PMID- 29042745
TI  - Immunoexpression of Ki-67 and Endoglin Corroborating Hamartomatous Nature of
      Sialoangiolipoma.
AB  - Mesenchymal neoplasms of salivary gland including adipocytes are relatively
      uncommon entity classified as monophasic and biphasic. Sialolipoma, a biphasic
      mesenchymal salivary gland neoplasm, with a prominent vascularity designated as
      sialoangiolipoma (SAL) is a recently discussed entity with debates on the
      hamartomatous nature of the lesion. We have endorsed the hamartomatous nature
      through evaluating the immunoexpression of Ki-67 and endoglin in SAL in hard
      palate of a 60-year-old patient. To the best of our knowledge, this would be the
      second case of SAL in hard palate in a global platform.

PMID- 29042746
TI  - Erratum: Comparative Alveolar Ridge Preservation Using Allogenous Tooth Graft
      versus Free-dried Bone Allograft: A Randomized, Controlled, Prospective, Clinical
      Pilot Study.
AB  - [This corrects the article on p. 211 in vol. 8, PMID: 28839405.].

PMID- 29042747
TI  - High-resolution wavefront-guided surface ablation with corneal cross-linking in
      ectatic corneas: a pilot study.
AB  - PURPOSE: A preliminary study to evaluate the outcomes of high-resolution
      wavefront-guided (HRWG) photorefractive keratectomy (PRK) with simultaneous
      corneal cross-linking (CXL) in ectasia eyes. METHODS: Sixteen eyes of 11 patients
      (mean age 31.9+/-9.8 years; range: 15-48 years) with keratoconus or post-laser
      assisted in situ keratomileusis ectasia underwent HRWG PRK with simultaneous CXL.
      Manifest refraction, uncorrected (UDVA) and corrected distance visual acuity
      (CDVA), and keratometric and aberrometric outcomes are reported at 12 months.
      RESULTS: Significant improvement was observed postoperatively in visual acuity,
      refraction, and keratectomy in all eyes. At postoperative 12 months, 87.5% eyes
      were within +/-1.0 D of attempted correction and 81.25% of eyes had a
      postoperative UDVA of 20/32 or better. A gain of 2 or more lines of CDVA was
      observed in 12.5% (2/16) of eyes and there was no change in CDVA lines in 25%
      (4/16) eyes. A substantial reduction in higher-order aberrations was observed in
      all eyes postoperatively; however, the improvement was not statistically
      significant. CONCLUSION: The outcomes of HRWG PRK in ectasia eyes with estimated
      residual stromal bed thickness of at least 350 MUm (without epithelium) are
      promising at postoperative 1 year and provide surgeons with a valuable tool to
      improve vision with a high degree of refractive predictability.

PMID- 29042748
TI  - Corneal biomechanical properties after laser-assisted in situ keratomileusis and
      photorefractive keratectomy.
AB  - BACKGROUND: The purpose of this study was to evaluate the effects of laser
      assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) on
      corneal biomechanical properties. METHODS: We used the ocular response analyzer
      to measure corneal hysteresis (CH) and corneal resistance factor (CRF) before and
      after refractive surgery. RESULTS: In all, 230 eyes underwent LASIK and 115 eyes
      underwent PRK without mitomycin C (MMC). Both procedures decreased CH and CRF
      from baseline. When MMC was used after PRK in 20 eyes, it resulted in lower
      corneal biomechanical properties at 3 months when compared to the other
      procedures, but all three procedures had similar values at 12 months. CONCLUSION:
      Significant but similar decreases in corneal biomechanical properties after
      LASIK, PRK without MMC, and PRK with MMC were noted.

PMID- 29042749
TI  - A review of results after implantation of a secondary intraocular lens to correct
      residual refractive error after cataract surgery.
AB  - PURPOSE: The purpose of this study was to provide clinical outcomes data related
      to secondary intraocular lens (IOL) implantation for the correction of residual
      refractive error after cataract surgery. PATIENTS AND METHODS: A chart review was
      conducted to identify all eyes implanted with the monofocal spherical or toric
      AddOn(r) secondary IOL. Data were collated from charts where uncomplicated
      initial cataract surgery was completed. Measures of interest included the
      original IOL implanted, the postoperative refractive error (before secondary IOL
      implantation) and the associated corrected and uncorrected visual acuities (VAs).
      Postoperative data of interest included the residual refractive error, the best
      corrected visual acuity (BCVA) and uncorrected visual acuity (UCVA). RESULTS:
      Refractive and VA data from 1 week to 3 months post-surgery were available for 46
      of 70 eyes implanted with a secondary IOL by one surgeon at one practice between
      4/15 and 3/17. There was a statistically significant improvement in UCVA of about
      2 lines after surgery (p<0.01), with no change in BCVA (p=0.94). No eyes lost a
      line of BCVA. There was a statistically significant reduction in the absolute
      magnitude of the residual spherical equivalent refractive error (p<0.01). In the
      10 cases with a toric secondary IOL, there was a statistically significant
      reduction in refractive cylinder (p<0.01). CONCLUSION: The secondary IOL studied
      here appears to be a viable surgical option to correct residual refractive error
      after primary IOL implantation.

PMID- 29042751
TI  - Spotlight on ertugliflozin and its potential in the treatment of type 2 diabetes:
      evidence to date.
AB  - Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the latest therapeutic
      strategy in the treatment of type 2 diabetes mellitus (T2DM). Using an insulin
      independent mechanism (glycosuria), they reduce glucose toxicity and improve
      insulin sensitivity and beta-cell function. The promising results obtained in
      clinical trials show that SGLT2 significantly improves glycemic control and
      provides greater cardiovascular protection, combined with a reduction in body
      weight and blood pressure (BP). This review focuses on ertugliflozin, a new,
      highly selective, and reversible SGLT2 inhibitor. Clinical trials published to
      date show that ertugliflozin, both as a monotherapy and as an add-on to oral
      antidiabetic agents, is safe and effective in reducing glycosylated hemoglobin
      (HbA1c), body weight, and BP in T2DM patients.

PMID- 29042752
TI  - Spotlight on perampanel in the management of seizures: design, development and an
      update on place in therapy.
AB  - PURPOSE: Perampanel is a first-in-class antiepileptic medication approved for the
      treatment of partial (focal) seizures, and as adjunctive treatment for primarily
      generalized tonic-clonic seizures. The pharmacology, efficacy data, adverse
      effect profile, pharmacokinetics and place in therapy are reviewed. SUMMARY:
      Perampanel is indicated for use in patients with epilepsy who are 12 years of age
      or older. It is the first medication designed specifically to be a non
      competitive antagonist at post-synaptic alpha-amino-3-hydroxyl-5-methyl-4
      isoxazole-propionate receptors. Efficacy in refractory seizures has been
      established, and ongoing efficacy demonstrated by post-marketing data. The drug
      is completely absorbed, and exhibits a half-life that allows for once-daily
      administration in doses up to 12 mg/day. Drug interactions are minimal, but
      increased doses may be necessary when given with strong inducers of cytochrome
      P450 enzymes, including when perampanel is co-administered with other
      antiepileptics that exhibit this property. The most common adverse effects noted
      in both clinical trials and post-marketing are dizziness and somnolence.
      Psychiatric and behavioral adverse events have been documented in both adult and
      pediatric patients, including those with no corresponding diagnostic history.
      CONCLUSION: Perampanel is a novel adjunctive antiepileptic medication that is an
      effective option for adolescents and adults with partial seizures, and primarily
      generalized tonic-clonic seizures uncontrolled with other medications.

PMID- 29042750
TI  - Current perspective on rituximab in rheumatic diseases.
AB  - The steadily increasing knowledge regarding pathogenetic mechanisms in autoimmune
      rheumatic diseases has paved the way to different therapeutic approaches. In
      particular, the market entry of biologics has dramatically modified the natural
      history of rheumatic chronic inflammatory diseases with a meaningful impact on
      patients' quality of life. Among the wide spectrum of available biological
      treatments, rituximab (RTX), first used in the treatment of non-Hodgkin's
      lymphoma, was later approved for rheumatoid arthritis and anti-neutrophil
      cytoplasmic antibodies-associated vasculitis. Nowadays, in rheumatology, RTX is
      also used with off-label indications in patients with systemic sclerosis,
      Sjogren's syndrome and systemic lupus erythematosus. RTX is a monoclonal antibody
      directed to CD20 molecules expressed on the surfaces of pre-B and mature B
      lymphocytes. It acts by causing apoptosis of these cells with antibody- and
      complement-dependent cytotoxicity. As inflammatory responses to cell-associated
      immune complexes are key elements in the pathogenesis of several autoimmune
      rheumatic diseases, such an approach might be effective in these patients. In
      fact, RTX, by promoting the rapid and long-term depletion of circulating and
      lymphoid tissue-associated B cells, leads to a lower recruitment of these
      effector cells at sites of immune complex deposition, thus reducing inflammation
      and tissue damage. RTX is of the most interest to rheumatologists as it
      represents an important additional therapeutic approach. Thus, the advent in
      clinical practice of approved RTX biosimilars, such as CT-P10, may be of help in
      improving treatment access as well as in reducing costs.

PMID- 29042754
TI  - Erratum: Patients' beliefs about adherence to oral antidiabetic treatment: a
      qualitative study [Corrigendum].
AB  - [This corrects the article on p. 413 in vol. 9, PMID: 25792814.].

PMID- 29042753
TI  - Functional and morphological effects of diazepam and midazolam on tumor
      vasculature in the 9L gliosarcoma brain tumor model using dynamic susceptibility
      contrast MRI: a comparative study.
AB  - Antiangiogenic therapy attenuates tumor growth by reducing vascularization.
      Diazepam (DZP) and midazolam (MZL) have antiangiogenic properties in human
      umbilical vein endothelial cells. Thus, we investigated the antiangiogenic
      activity of DZP and MZL in the rat 9L gliosarcoma brain tumor model. The effect
      on tumor vasculature was evaluated using dynamic susceptibility contrast magnetic
      resonance imaging with gradient-echo (GE) and spin-echo (SE) to assess perfusion
      parameters, including cerebral blood volume (CBV), cerebral blood flow (CBF),
      mean transit time (MTT), and mean vessel diameter. The GE-normalized CBF (nCBF)
      in the tumors of untreated controls was significantly lower than that in normal
      brain tissue, whereas the CBV and MTT were higher. DZP- and MZL-treated rats had
      higher CBF and lower CBV and MTT values than did untreated controls. The tumor
      size decreased significantly to 33.5% in DZP-treated rats (P<0.001) and 22.5% in
      MZL-treated rats (P<0.01) relative to controls. The SE-normalized CBV was lower
      in DZP-treated (32.9%) and MZL-treated (10.6%) rats compared with controls. The
      mean vessel diameter decreased significantly by 32.5% in DPZ-treated and by 24.9%
      in MZL-treated rats compared with controls (P<0.01). The GE and SE nCBF values
      were higher in DZP-treated (49.9% and 40.1%, respectively) and MZL-treated (41.2%
      and 32.1%, respectively) rats than in controls. The GE- and SE-normalized MTTs
      were lower in DZP-treated (48.2% and 59.8%, respectively) and MZL-treated (40.5%
      and 51.2%, respectively) rats than in controls. Both DZP and MZL had
      antiangiogenic effects on tumor perfusion and vasculature; however, the
      antiangiogenic activity of DZP is more promising than that of MZL.

PMID- 29042755
TI  - Clinical data combined with radiological imaging improves the accuracy of TNM
      staging of pancreatic body and tail adenocarcinoma.
AB  - PURPOSE: Pancreatic body and tail adenocarcinoma (PBTA) remains one of the
      deadliest cancers, and current radiological modalities still have limitations on
      the staging of PBTA. Improving PBTA staging will contribute to the management of
      this disease. PATIENTS AND METHODS: Clinicopathological characteristics of 91
      surgically treated PBTA patients were retrospectively retrieved. Clinical data
      associated with postoperative tumor staging (pTNM) were assessed using ordinal
      logistic regression model. Discriminant analysis was performed using function
      formula based on multivariate analysis results; further cross-validation was
      conducted by Bootstrap methods. RESULTS: Multivariate analysis showed that
      carbohydrate antigen 19-9 >=955.0 U/L, albumin, and alkaline phosphatase/total
      bilirubin ratio were independent factors contributing to improved accuracy of
      pTNM staging. Discriminant analysis exhibited better performance and showed that
      the probability of accurate prediction of pTNM stage was 90.6% and the
      probability of cross-validation was 85.9%. After excluding patients with
      preoperative diagnosis of stage IV disease, the probability of accurate
      prediction of pTNM stage was 86.1% and the probability of cross-validation was
      75.0%. CONCLUSION: The combination of imaging and clinical data has higher
      accuracy in staging PBTA than radiological data alone. A model proposed in this
      study will improve the management of PBTA.

PMID- 29042756
TI  - Psychological intervention improves life quality of patients with laryngeal
      cancer.
AB  - BACKGROUND: The purpose of this study is to examine the effect of psychological
      intervention on the life quality of patients with laryngeal cancer. METHODS: Two
      hundred and ten patients with laryngeal cancer were randomly assigned to the
      study group receiving psychological intervention and control group receiving
      routine nursing care. The Hamilton Depression Scale (HAMD), Hamilton Anxiety
      Scale (HAMA), and the Europe Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire (EORTC QLQ-C30) were used to evaluate life quality.
      RESULTS: There were no significant differences in the scores of HAMD, HAMA, and
      EORTC QLQ-C30 between the 2 groups before treatment (P>0.05). After treatment,
      the scores in the study group were significantly different to those in the
      control group (P<0.05). In addition, the satisfaction rate and compliance rate of
      patients in the study group were increased, compared to the control group
      (P<0.05). CONCLUSION: Psychological intervention is beneficial in improving life
      quality in patients with laryngeal cancer after surgery.

PMID- 29042757
TI  - Cognitive deficits and self-care behaviors in elderly adults with heart failure.
AB  - INTRODUCTION: Elderly adults with heart failure (HF) may have problems with self
      care behaviors because of cognitive deficits. Self-care deficits have been found
      to be significantly associated with negative health care outcomes among HF
      patients. The aim of this paper was to assess cognitive deficits and the level of
      self-care ability in elderly patients with HF, and to determine if a relationship
      exists between cognitive deficits and self-care. MATERIALS AND METHODS: The study
      included 270 elderly patients (mean age: 72.5 years) with HF. We used the Mini
      Mental State Examination Scale (MMSE) to evaluate cognitive functioning, and the
      European Heart Failure Self-care Behavior Scale, revised into a nine-item scale
      (EHFScBS-9), to evaluate self-care behaviors. Associations between the variables
      were examined using multiple regression analysis. RESULTS: Lower scores in both
      MMSE and EHFScBS-9 questionnaires were correlated with older age, living alone,
      lower education, longer duration of illness, higher number of rehospitalizations,
      as well as lower left ventricular ejection fraction and higher New York Heart
      Association (NYHA) class. The multiple regression analysis was used for
      evaluation of the impact of the following predictors: MMSE score, age, duration
      of illness, ejection fraction, number of hospitalizations, sex, residence,
      education, relationship status, and NYHA class on EHFScBS-9 score. CONCLUSIONS:
      Elderly patients with HF may have worse self-care behaviors because of their
      cognitive deficits. Age was the strongest predictor of worse MMSE scores.
      Multidisciplinary health teams should pay attention to the special needs of
      elderly patients who live with their illness for many years and have no social
      support because of living alone.

PMID- 29042758
TI  - Prescribing of psychotropic medication for nursing home residents with dementia:
      a general practitioner survey.
AB  - OBJECTIVE: The aim of this study was to identify factors influencing the
      prescribing of psychotropic medication by general practitioners (GPs) to nursing
      home residents with dementia. SUBJECTS AND METHODS: GPs with experience in
      nursing homes were recruited through professional body newsletter advertising,
      while 1,000 randomly selected GPs from southeastern Australia were invited to
      participate, along with a targeted group of GPs in Tasmania. An anonymous survey
      was used to collect GPs' opinions. RESULTS: A lack of nursing staff and resources
      was cited as the major barrier to GPs recommending non-pharmacological techniques
      for behavioral and psychological symptoms of dementia (BPSD; cited by 55%;
      78/141), and increasing staff levels at the nursing home ranked as the most
      important factor to reduce the usage of psychotropic agents (cited by 60%;
      76/126). CONCLUSION: According to GPs, strategies to reduce the reliance on
      psychotropic medication by nursing home residents should be directed toward
      improved staffing and resources at the facilities.

PMID- 29042759
TI  - Early and intermediate age-related macular degeneration: update and clinical
      review.
AB  - Age-related macular degeneration (AMD) is the leading cause of irreversible
      central vision loss in developed countries. With the aging of population, AMD
      will become globally an increasingly important and prevalent disease worldwide.
      It is a complex disease whose etiology is associated with both genetic and
      environmental risk factors. An extensive decline in the quality of life and
      progressive need of daily living assistance resulting from AMD among those most
      severely affected highlights the essential role of preventive strategies,
      particularly advising patients to quit smoking. In addition, maintaining a
      healthy diet, controlling other risk factors (such as hypertension, obesity, and
      atherosclerosis), and the use of nutritional supplements (antioxidants) are
      recommendable. Genetic testing may be especially important in patients with a
      family history of AMD. Recently, unifying criteria for the clinical
      classification of AMD, defining no apparent aging changes; normal aging changes;
      and early, intermediate, and late AMD stages, are of value in predicting AMD risk
      of progression and in establishing recommendations for the diagnosis, therapeutic
      approach, and follow-up of patients. The present review is focused on early and
      intermediate AMD and presents a description of the clinical characteristics and
      ophthalmological findings for these stages, together with algorithms for the
      diagnosis and management of patients, which are easily applicable in daily
      clinical practice.

PMID- 29042760
TI  - A scoping review of crisis teams managing dementia in older people.
AB  - BACKGROUND: Research on crisis teams for older adults with dementia is limited.
      This scoping review aimed to 1) conduct a systematic literature review reporting
      on the effectiveness of crisis interventions for older people with dementia and
      2) conduct a scoping survey with dementia crisis teams mapping services across
      England to understand operational procedures and identify what is currently
      occurring in practice. METHODS: For the systematic literature review, included
      studies were graded using the Critical Appraisal Skills Programme checklist. For
      the scoping survey, Trusts across England were contacted and relevant services
      were identified that work with people with dementia experiencing a mental health
      crisis. RESULTS: The systematic literature review demonstrated limited evidence
      in support of crisis teams reducing the rate of hospital admissions, and despite
      the increase in number of studies, methodological limitations remain. For the
      scoping review, only half (51.8%) of the teams had a care pathway to manage
      crises and the primary need for referral was behavioral or psychological factors.
      CONCLUSION: Evidence in the literature for the effectiveness of crisis teams for
      older adults with dementia remains limited. Being mainly cohort designs can make
      it difficult to evaluate the effectiveness of the intervention. In practice, it
      appears that the pathway for care managing crisis for people with dementia varies
      widely across services in England. There was a wide range of names given to the
      provision of teams managing crisis for people with dementia, which may reflect
      the differences in the setup and procedures of the service. To provide evidence
      on crisis intervention teams, a comprehensive protocol is required to deliver a
      standardized care pathway and measurable intervention as part of a large-scale
      evaluation of effectiveness.

PMID- 29042761
TI  - Understanding institutional stakeholders' perspectives on multidrug-resistant
      bacterial organism at the end of life: a qualitative study.
AB  - BACKGROUND: Information lacks about institutional stakeholders' perspectives on
      management approaches of multidrug-resistant bacterial organism in end-of-life
      situations. The term "institutional stakeholder" includes persons in leading
      positions with responsibility in hospitals' multidrug-resistant bacterial
      organism management. They have great influence on how strategies on multidrug
      resistant bacterial organism management approaches in institutions of the public
      health system are designed. This study targeted institutional stakeholders'
      individual perspectives on multidrug-resistant bacterial organism colonization or
      infection and isolation measures at the end of life. METHODS: Between March and
      December 2014, institutional stakeholders of two study centers, a German
      palliative care unit and a geriatric ward, were queried in semistructured
      interviews. Interviews were audiotaped, transcribed verbatim, and analyzed
      qualitatively with the aid of the software MAXQDA for qualitative data analysis
      using principles of Grounded Theory. In addition, two external stakeholders were
      interviewed to enrich data. RESULTS: Key issues addressed by institutional
      stakeholders (N=18) were the relevance of multidrug-resistant bacterial organism
      in palliative and geriatric care, contradictions between hygiene principles and
      patients' and family caregivers' needs and divergence from standards, frame
      conditions, and reflections on standardization of multidrug-resistant bacterial
      organism end-of-life care procedures. Results show that institutional
      stakeholders face a dilemma between their responsibility in protecting third
      persons and ensuring patients' quality of life. Until further empirical evidence
      establishes a clear multidrug-resistant bacterial organism management approach in
      end-of-life care, stakeholders suggest a case-based approach. CONCLUSION: The
      institutional stakeholders' perspectives and their suggestion of a case-based
      approach advance the development process of a patient-, family-, staff-, and
      institutional-centered approach of how to deal with multidrug-resistant bacterial
      organism-positive patients in end-of-life care. Institutional stakeholders play
      an important role in the implementation of recommendations following this
      approach.

PMID- 29042762
TI  - Assessing the nutritional status of hospitalized elderly.
AB  - PURPOSE: The increasing number of elderly people worldwide throughout the years
      is concerning due to the health problems often faced by this population. This
      review aims to summarize the nutritional status among hospitalized elderly and
      the role of the nutritional assessment tools in this issue. METHODS: A literature
      search was performed on six databases using the terms "malnutrition",
      "hospitalised elderly", "nutritional assessment", "Mini Nutritional Assessment
      (MNA)", "Geriatric Nutrition Risk Index (GNRI)", and "Subjective Global
      Assessment (SGA)". RESULTS: According to the previous studies, the prevalence of
      malnutrition among hospitalized elderly shows an increasing trend not only
      locally but also across the world. Under-recognition of malnutrition causes the
      number of malnourished hospitalized elderly to remain high throughout the years.
      Thus, the development of nutritional screening and assessment tools has been
      widely studied, and these tools are readily available nowadays. SGA, MNA, and
      GNRI are the nutritional assessment tools developed specifically for the elderly
      and are well validated in most countries. However, to date, there is no single
      tool that can be considered as the universal gold standard for the diagnosis of
      nutritional status in hospitalized patients. CONCLUSION: It is important to
      identify which nutritional assessment tool is suitable to be used in this group
      to ensure that a structured assessment and documentation of nutritional status
      can be established. An early and accurate identification of the appropriate
      treatment of malnutrition can be done as soon as possible, and thus, the
      malnutrition rate among this group can be minimized in the future.

PMID- 29042763
TI  - Quality of life and physical activity in an older working-age population.
AB  - OBJECTIVE: Physical activity can be an effective means of prevention and therapy
      of many psychosomatic disorders. It can also have a significant impact on the
      quality of life of older working-age people. The aim of the present study was to
      assess the relationships between quality of life and physical activity in older
      working-age people from Wroclaw, Poland. MATERIALS AND METHODS: The study group
      comprised 1,013 people, including 565 women and 448 men, aged 55-64 years (59.1+/
      2.9 years). The study took form of a questionnaire survey. The participants
      assessed their physical activity and quality of life using the International
      Physical Activity Questionnaire Short Version (IPAQ-SF) and the World Health
      Organization Quality of Life (WHOQOL-BREF), respectively. RESULTS: The highest
      mean indices of general quality of life, perceived health status, and quality of
      life in the physical, psychological, social, and environmental domains were shown
      by respondents whose intensity of physical activity was the highest. Moreover,
      the odds of high assessment of overall quality of life increased with
      respondents' higher levels of physical activity. CONCLUSION: Quality of life
      improvement programs should also involve increased physical activity components.

PMID- 29042764
TI  - The association between objectively measured physical activity and morning
      symptoms in COPD.
AB  - PURPOSE: The morning is the most bothersome period for COPD patients. Morning
      symptom severities in different Global Initiative for Chronic Obstructive Lung
      Disease (GOLD) stages are not well studied. Furthermore, factors that are
      associated with morning symptoms, especially the associations with objectively
      measured physical activity, are also not well described. MATERIALS AND METHODS:
      The aim of this cross-sectional observational study was to assess morning symptom
      severity in GOLD A, B, C and D patients, according to the definitions of the GOLD
      2015 statement. Morning symptoms were assessed with the PRO-Morning COPD Symptoms
      Questionnaire. Differences in morning symptom severity between different COPD
      stages were assessed with a one-way analysis of variance followed by post hoc
      analyses. The association between dyspnea severity (assessed with the modified
      Medical Research Council scale), health status, airflow limitation, lung
      hyperinflation, anxiety and depression, inflammatory parameters, exacerbations,
      objectively measured physical activity parameters retrieved from accelerometry
      and morning symptom severity was evaluated using linear regression analysis.
      RESULTS: Eighty patients were included (aged 65.6+/-8.7 years, forced expiratory
      volume in 1 second [FEV1] % predicted 55.1+/-16.9). Mean (+/-SD) morning symptom
      score was 19.7 (+/-11.7). Morning symptom severity was significantly different
      between COPD stages: mean (+/-SD) score in GOLD A was 9.7 (+/-7.2), in GOLD B
      19.8 (+/-10.7), in GOLD C 8.6 (+/-9.3) and in GOLD D 23.8 (+/-11.2) (p<0.001).
      Lower health status, more symptoms, increased anxiety and depression, less
      physical activity (all p<0.001) and lower FEV1 (p=0.03) were associated with an
      increased morning symptom severity. CONCLUSION: Patients with overall more
      symptomatic COPD have significant higher morning symptom scores. Morning symptom
      severity was associated with important clinical outcomes: lower health status,
      more symptoms, increased anxiety and depression, fewer steps a day, less time in
      moderate and vigorous physical activity with bouts of at least 10 minutes and
      lower FEV1. The data suggest that morning symptoms should be carefully assessed
      in addition to assessment by general COPD-specific questionnaires, especially in
      those with more symptomatic COPD. More research is needed on potential therapies
      to improve morning symptoms; this study shows potential targets for intervention.

PMID- 29042765
TI  - Risk of cancer after lung transplantation for COPD.
AB  - BACKGROUND: The risk of cancer is increased and affects survival after lung
      transplantation (LTx), but has not been well characterized in COPD. We aimed to
      evaluate the incidence and prognosis of cancer following LTx for COPD. METHODS: A
      prospective, population-based study of patients undergoing LTx for end-stage COPD
      at the two transplantation centers in Sweden between 1990-2013, with follow-up
      for incident cancer and death, using national registers. The excess risk of
      cancer was calculated as standardized incidence ratios compared with the general
      population matched for age, sex, and calendar year. Risk factors for cancer were
      analyzed using Fine-Gray regression, and survival after cancer diagnosis with
      Kaplan-Meier. RESULTS: In total, 331 patients (mean age 55.4 years; 64% women;
      97% former smokers) were included. At a median follow-up of 2.8 years, 35% of
      patients had developed cancer and the risk was increased more than 10-fold ([95%
      CI] 8.1-11.8). The highest excess risks were for non-Hodgkin lymphoma (20.8
      66.7), skin cancer (20.3-35.2), lung (11.7-31.2), liver (3.6-51.6), and
      colorectal cancer (6.1-19.5). Median survival was longer for skin cancer (8
      years; 95% CI, 3-15) compared with non-skin cancer (4 years; 95% CI, 2.8-4.8;
      p<0.001). CONCLUSION: The cancer risk is markedly increased after LTx for COPD.
      It could not be predicted by the factors evaluated, but contributed significantly
      to a negative prognosis.

PMID- 29042766
TI  - Use of the forced-oscillation technique to estimate spirometry values.
AB  - PURPOSE: Spirometry is sometimes difficult to perform in elderly patients and in
      those with severe respiratory distress. The forced-oscillation technique (FOT) is
      a simple and noninvasive method of measuring respiratory impedance. The aim of
      this study was to determine if FOT data reflect spirometric indices. PATIENTS AND
      METHODS: Patients underwent both FOT and spirometry procedures prior to inclusion
      in development (n=1,089) and validation (n=552) studies. Multivariate linear
      regression analysis was performed to identify FOT parameters predictive of vital
      capacity (VC), forced VC (FVC), and forced expiratory volume in 1 second (FEV1).
      A regression equation was used to calculate estimated VC, FVC, and FEV1. We then
      determined whether the estimated data reflected spirometric indices. Agreement
      between actual and estimated spirometry data was assessed by Bland-Altman
      analysis. RESULTS: Significant correlations were observed between actual and
      estimated VC, FVC, and FEV1 values (all r>0.8 and P<0.001). These results were
      deemed robust by a separate validation study (all r>0.8 and P<0.001). Bias
      between the actual data and estimated data for VC, FVC, and FEV1 in the
      development study was 0.007 L (95% limits of agreement [LOA] 0.907 and -0.893 L),
      -0.064 L (95% LOA 0.843 and -0.971 L), and -0.039 L (95% LOA 0.735 and -0.814 L),
      respectively. On the other hand, bias between the actual data and estimated data
      for VC, FVC, and FEV1 in the validation study was -0.201 L (95% LOA 0.62 and 
      1.022 L), -0.262 L (95% LOA 0.582 and -1.106 L), and -0.174 L (95% LOA 0.576 and 
      0.923 L), respectively, suggesting that the estimated data in the validation
      study did not have high accuracy. CONCLUSION: Further studies are needed to
      generate more accurate regression equations for spirometric indices based on FOT
      measurements.

PMID- 29042767
TI  - Effectiveness of treatment with nebulized colistin in patients with COPD.
AB  - OBJECTIVES: To analyze whether the introduction of nebulized colistin in patients
      with chronic obstructive pulmonary disease (COPD) and infection with Pseudomonas
      aeruginosa (PA) is associated with a decrease of the number and duration of
      severe exacerbations. MATERIALS AND METHODS: Thirty six patients with COPD and
      infection with PA treated with nebulized colistin attending a day hospital during
      a 5-year (January 2010-December 2014) period were prospectively included.
      Repeated-measures t-tests were used to assess whether the introduction of
      colistin was associated with changes in the number of exacerbations or the length
      of the hospitalizations, comparing for each patient the year prior to the
      introduction of colistin with the year after. RESULTS: After the introduction of
      colistin, the number of admissions decreased from 2.0 to 0.9 per individual year
      (P=0.0007), and hospitalizations were shorter (23.3 vs 10.9 days, P=0.00005).
      These results persisted when patients with and without bronchiectasis or with and
      without persistence of Pseudomonas were separately analyzed. No pre-post
      differences were detected in the number of exacerbations not requiring admission.
      CONCLUSION: Nebulized colistin seems associated with a strong decrease in the
      number and duration of hospitalizations due to exacerbation in patients with COPD
      and infection with PA. Clinical trials with a larger number of patients are
      needed in order to confirm these results.

PMID- 29042768
TI  - Systemic toxicity induced by aggregated layered double hydroxide nanoparticles.
AB  - Layered double hydroxide (LDH) nanoparticles are emerging as one of the promising
      nanomaterials for biomedical applications, but their systemic toxicity in vivo
      has received little attention. In the present study, the effects of inorganic
      nanoparticle aggregation on their systemic toxicity were examined. Remarkably,
      aggregation was observed after the mixing of naked LDH nanoparticles with saline
      or erythrocytes. Significant accumulation of the naked LDH nanoparticles in the
      lungs of mice was detected 1 h after intravenous administration, and the survival
      rate of mice was 0% after 6 repeated injections. Furthermore, flocculent
      precipitates in the alveoli and congestion in the lung interstitium were observed
      in the dead mice. However, lipid membrane-coated LDH nanoparticles would not form
      aggregates and could be injected intravenously >6 times without causing death.
      These findings suggested that repeated injections of LDH were lethal even at low
      dose (30 mg/kg), and lipid membrane coating can be considered as an approach for
      reducing this risk.

PMID- 29042769
TI  - Bioabsorbable self-retaining PLA/nano-sized beta-TCP cervical spine interbody
      fusion cage in goat models: an in vivo study.
AB  - STUDY DESIGN: This is an experimental animal study. OBJECTIVE: The objective of
      this study was to compare an anterior cervical discectomy and interbody fusion of
      a novel polylactide/nano-sized beta-tricalcium phosphate (PLA/nbeta-TCP)
      bioabsorbable self-retaining cervical fusion cage (BCFC) with an autologous bone
      graft and polyetheretherketone (PEEK) cages. BACKGROUND: Although PLA cervical
      cages have potential advantages compared with traditional materials, they are not
      currently routinely used in spine surgery because of undesirable effects such as
      the lack of osteoconductivity and osteolysis around the implant. This study
      involved the manufacturing of a bioabsorbable cage from PLA/nbeta-TCP that was
      then used as a device for anterior cervical discectomy and fusion (ACDF) on a
      goat cervical spine fusion model. MATERIALS AND METHODS: Eighteen goats underwent
      C3/C4 discectomy and were randomly divided into three groups based on the
      following methods: Group A (n=6), an autologous bone graft; Group B (n=6), PEEK
      cage filled with an autologous graft; and Group C (n=6), BCFC filled with an
      autologous iliac bone. Radiography was performed preoperatively and
      postoperatively and at 1, 4, 8, and 12 weeks after the operation. Disc space
      height (DSH) was measured at the same time. After 12 weeks, the fused segments
      were harvested and evaluated with functional radiographic views, biomechanical
      testing, and histological analyses. RESULTS: Over a 12-week period, the BCFC and
      PEEK cage groups exhibited significantly higher DSH values than the bone graft
      group. Additionally, the BCFC group yielded a significantly lower range of motion
      in axial rotation than both the autologous bone graft and PEEK cage groups. A
      histologic evaluation revealed an increased intervertebral bone volume/total
      volume ratio and better interbody fusion in the BCFC group than in the other
      groups. CONCLUSION: The BCFC device exhibited better results than the autologous
      bone graft and PEEK cages in single-level ACDF models in vivo. This device may be
      a potential alternative to the current PEEK cages.

PMID- 29042770
TI  - BSA-assisted synthesis of ultrasmall gallic acid-Fe(III) coordination polymer
      nanoparticles for cancer theranostics.
AB  - Protein-related nanotheranostic agents hold great promise as tools to serve many
      clinical applications. Proteins such as BSA are used to regulate the synthesis of
      nondegradable inorganic nanoparticles (NPs). To fully employ the potential of
      such proteins, a new type of biosafe nanotheranostic agent must be designed to
      optimize BSA as a biomineralization agent. Here, a straightforward BSA-assisted
      biomineralization method was developed to prepare gallic acid (GA)-Fe(III)
      coordination polymer NPs. BSA-coated GA-Fe (GA-Fe@BSA) NPs were ultrasmall (3.5
      nm) and showed good biocompatibility, a lower r2:r1 ratio (1.06), and strong
      absorption in the visible near-infrared region. T1-weighted magnetic resonance
      imaging of tumor-bearing mice before and after intratumoral injection with GA
      Fe@BSA NPs definitively demonstrated positive change. In a subsequent in vivo
      study, antitumor activity was precipitated by intratumoral injection of GA-Fe@BSA
      NPs combined with laser treatment, suggesting excellent outcomes with this
      treatment method. These results describe a successful protocol in which BSA
      regulated the synthesis of benign organic polymer NPs. GA-Fe@BSA NPs have the
      potential to be ideal agents to be used in clinical theranostic nanoplatforms.

PMID- 29042772
TI  - Erratum: Polyethylenimine-based micro/nanoparticles as vaccine adjuvants
      [Corrigendum].
AB  - [This corrects the article on p. 5443 in vol. 12, PMID: 28814862.].

PMID- 29042771
TI  - Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine
      xenograft model of triple negative breast cancer.
AB  - Patients with triple negative breast cancer have a poor prognosis due in part to
      the lack of targeted therapies. In the search for novel drugs, our laboratory has
      developed a second-generation curcumin derivative, 3,5-bis(3,4,5
      trimethoxybenzylidene)-1-methylpiperidine-4-one (RL71), that exhibits potent in
      vitro cytotoxicity. To improve the clinical potential of this drug, we have
      encapsulated it in styrene maleic acid (SMA) micelles. SMA-RL71 showed improved
      biodistribution, and drug accumulation in the tumor increased 16-fold compared to
      control. SMA-RL71 (10 mg/kg, intravenously, two times a week for 2 weeks) also
      significantly suppressed tumor growth compared to control in a xenograft model of
      triple negative breast cancer. Free RL71 was unable to alter tumor growth. Tumors
      from SMA-RL71-treated mice showed a decrease in angiogenesis and an increase in
      apoptosis. The drug treatment also modulated various cell signaling proteins
      including the epidermal growth factor receptor, with the mechanisms for tumor
      suppression consistent with previous work with RL71 in vitro. The nanoformulation
      was also nontoxic as shown by normal levels of plasma markers for liver and
      kidney injury following weekly administration of SMA-RL71 (10 mg/kg) for 90 days.
      Thus, we report clinical potential following encapsulation of a novel curcumin
      derivative, RL71, in SMA micelles.

PMID- 29042773
TI  - Diamond, graphite, and graphene oxide nanoparticles decrease migration and
      invasiveness in glioblastoma cell lines by impairing extracellular adhesion.
AB  - The highly invasive nature of glioblastoma is one of the most significant
      problems regarding the treatment of this tumor. Diamond nanoparticles (ND),
      graphite nanoparticles (NG), and graphene oxide nanoplatelets (nGO) have been
      explored for their biomedical applications, especially for drug delivery. The
      objective of this research was to assess changes in the adhesion, migration, and
      invasiveness of two glioblastoma cell lines, U87 and U118, after ND, NG, and nGO
      treatment. All treatments affected the cell surface structure, adhesion-dependent
      EGFR/AKT/mTOR, and beta-catenin signaling pathways, decreasing the migration and
      invasiveness of both glioblastoma cell lines. The examined nanoparticles did not
      show strong toxicity but effectively deregulated cell migration. ND was
      effectively taken up by cells, whereas nGO and NG strongly interacted with the
      cell surface. These results indicate that nanoparticles could be used in
      biomedical applications as a low toxicity active compound for glioblastoma
      treatment.

PMID- 29042774
TI  - Reductive nanocomplex encapsulation of cRGD-siRNA conjugates for enhanced
      targeting to cancer cells.
AB  - In this study, through covalent conjugation and lipid material entrapment, a
      combined modification strategy was established for effective delivery of small
      interfering RNA (siRNA). Single strands of siRNA targeting to BRAFV600E gene
      (siMB3) conjugated with cRGD peptide at 3'-terminus or 5'-terminus via cleavable
      disulfide bond was synthesized and then annealed with corresponding strands to
      obtain single and bis-cRGD-siRNA conjugates. A cationic lipid material (CLD)
      developed by our laboratory was mixed with the conjugates to generate
      nanocomplexes; their uniformity and electrical property were revealed by particle
      size and zeta potential measurement. Compared with CLD/siBraf, CLD/cRGD-siBraf
      achieved higher cell uptake and more excellent tumor-targeting ability,
      especially 21 (sense-5'/antisense-3"-cRGD-congjugate) nanocomplex. Moreover, they
      can regulate multiple pathways to varying degree and reduce acidification of
      endosome. Compared with the gene silencing of different conjugates, single or bis
      cRGD-conjugated siRNA showed little differences except 22 (5/5) which cRGD was
      conjugated at 5'-terminus of antisense strand and sense strand. However bis-cRGD
      conjugate 21 nanocomplex exhibited better specific target gene silencing at
      multiple time points. Furthermore, the serum stabilities of the bis-cRGD
      conjugates were higher than those of the single-cRGD conjugates. In conclusion,
      all these data suggested that CLD/bis-conjugates, especially CLD/21, can be an
      effective system for delivery of siRNA to target BRAFV600E gene for therapy of
      melanoma.

PMID- 29042775
TI  - Mesoporous composite nanoparticles for dual-modality ultrasound/magnetic
      resonance imaging and synergistic chemo-/thermotherapy against deep tumors.
AB  - High-intensity focused ultrasound (HIFU) is a promising and noninvasive treatment
      for solid tumors, which has been explored for potential clinical applications.
      However, the clinical applications of HIFU for large and deep tumors such as
      hepatocellular carcinoma (HCC) are severely limited by unsatisfactory imaging
      guidance, long therapeutic times, and damage to normal tissue around the tumor
      due to the high power applied. In this study, we developed
      doxorubicin/perfluorohexane-encapsulated hollow mesoporous Prussian blue
      nanoparticles (HMPBs-DOX/PFH) as theranostic agents, which can effectively guide
      HIFU therapy and enhance its therapeutic effects in combination with
      chemotherapy, by decreasing the cavitation threshold. We investigated the effects
      of this agent on ultrasound and magnetic resonance imaging in vitro and in vivo.
      In addition, we showed a highly efficient HIFU therapeutic effect against HCC
      tumors, as well as controlled drug release, owing to the phase-transitional
      performance of the PFH. We therefore conclude that HMPB-DOX/PFH is a safe and
      efficient nanoplatform, which holds significant promise for cancer theranostics
      against deep tumors in clinical settings.

PMID- 29042777
TI  - Self-rated cognitive functions following chemotherapy in patients with breast
      cancer: a 6-month prospective study.
AB  - PURPOSE: The purpose of the study was to evaluate subjective (self-rated), family
      rated, and objective (researcher-rated) cognitive functions in patients with
      breast cancer after chemotherapy. METHOD: We conducted a prospective study to
      trace self-rated cognitive functions in 30 patients with breast cancer at the
      completion of chemotherapy (T0) and 6 months later (T1). Subjective cognitive
      functions were assessed with Cognitive Failures Questionnaire (CFQ), Dysexecutive
      Questionnaire (DEX-S), and Everyday Memory Checklist (EMC-S) for attention,
      executive function, and episodic memory, respectively. Their family members also
      completed DEX-I and EMC-I for executive function and episodic memory,
      respectively. We also examined objective cognitive functions. Self-rated
      cognitive functions were compared with the normative data. They were compared
      between T0 and T1. We calculated correlation coefficients between self-rated and
      other cognitive functions. RESULTS: At T0, 6 (20.0%) and 2 (6.7%) participants
      showed higher DEX-S and EMC-S scores than the normative data, respectively, while
      no participant had abnormal CFQ scores. At T1, DEX-S and EMC-S scores were
      normalized in 3 (50.0%) and 2 (100.0%) participants, respectively. No participant
      showed increases in CFQ scores. No changes were found in objective cognitive
      functions from T0 to T1. DEX-S and DEX-I or EMC-S and EMC-I scores were
      correlated at both T0 and T1, which did not survive multiple corrections. There
      was no association between subjective and objective cognitive functions.
      CONCLUSION: Impairments in subjective cognition may be transient after
      chemotherapy in patients with breast cancer. Furthermore, patients and their
      families appear to share similar prospects on their cognitive functions.

PMID- 29042778
TI  - Motivation to change and posttreatment temptation to drink: a multicenter study
      among alcohol-dependent patients.
AB  - BACKGROUND: An inpatient 28-day rehabilitation program for alcohol dependence is
      focused on detoxification, enhancing motivation to change, and coping strategies
      for the management of emotional distress and temptation to drink. The aims of the
      present study were to investigate 1) changes over time in motivation to change,
      anxiety, and depression in individuals undergoing residential rehabilitation
      treatment for alcohol addiction, and 2) which pretreatment factors are associated
      with posttreatment temptation to drink. METHODS: We assessed 432 patients
      diagnosed with alcohol dependence based on the Diagnostic and Statistical Manual
      of Mental Disorders (Fourth Edition, Text Revision) consecutively recruited from
      seven residential rehabilitation centers in Northern Italy. Patients were
      assessed by means of self-report questionnaires at the beginning of
      rehabilitation (pretreatment) and before their hospital discharge (posttreatment)
      regarding motivation to change and self-efficacy (motivation assessment of change
      - alcoholism version), readiness to change and temptation to drink (visual analog
      scales), and depression and anxiety (cognitive behavioral assessment - outcome
      evaluation). RESULTS: Results showed an overall improvement in motivation to
      change and a significant reduction over time in depression and anxiety levels for
      the total sample, particularly patients with low baseline level of temptation to
      drink. Multivariate linear regression analysis revealed that significant
      predictors of posttreatment temptation to drink were polysubstance dependence
      (p<0.001), readiness to change (p=0.01), and self-efficacy (p=0.05). CONCLUSION:
      Inpatients' rehabilitation for alcohol dependence is associated with an overall
      improvement in motivation to change and a significant reduction of psychological
      distress. Treatments for alcohol-dependent patients should focus on motivation to
      change, negative moods, and relapse prevention strategies for the management of
      craving.

PMID- 29042776
TI  - Effective use of nanocarriers as drug delivery systems for the treatment of
      selected tumors.
AB  - Nanotechnology has recently gained increased attention for its capability to
      effectively diagnose and treat various tumors. Nanocarriers have been used to
      circumvent the problems associated with conventional antitumor drug delivery
      systems, including their nonspecificity, severe side effects, burst release and
      damaging the normal cells. Nanocarriers improve the bioavailability and
      therapeutic efficiency of antitumor drugs, while providing preferential
      accumulation at the target site. A number of nanocarriers have been developed;
      however, only a few of them are clinically approved for the delivery of antitumor
      drugs for their intended actions at the targeted sites. The present review is
      divided into three main parts: first part presents introduction of various
      nanocarriers and their relevance in the delivery of anticancer drugs, second part
      encompasses targeting mechanisms and surface functionalization on nanocarriers
      and third part covers the description of selected tumors, including breast,
      lungs, colorectal and pancreatic tumors, and applications of relative
      nanocarriers in these tumors. This review increases the understanding of tumor
      treatment with the promising use of nanotechnology.

PMID- 29042779
TI  - Comparison of duloxetine and SSRI as a treatment option of painful physical
      symptoms associated with major depressive disorder.

PMID- 29042780
TI  - Frequencies of circulating B- and T-lymphocytes as indicators for stroke
      outcomes.
AB  - BACKGROUND: Stroke has high mortality and morbidity. Biomarkers are required for
      to predict stroke outcomes, which could help clinicians to provide rationale
      approaches for patient management. The dynamic changes in circulating immune
      cells have been reported in stroke patients and animal models of stroke. AIM: The
      aim of this study was to explore biomarkers to predict stroke outcomes by
      investigating the relationship between the frequencies of circulating immune
      cells and stroke outcomes. METHODS: In all, 50 acute ischemic stroke (AIS)
      patients were enrolled. Their blood samples were collected upon hospital
      admission and on day 1 and day 7 after stroke, and the leukocyte subsets were
      analyzed by flow cytometry. The dynamic changes in some types of immune cells in
      the AIS course and their correlation with clinical parameters were analyzed.
      Blood samples from 123 age- and gender-matched healthy subjects were used as
      controls. RESULTS: The proportions of T-lymphocytes and NK cells in stroke
      patients were significantly lower than in healthy controls. The frequencies of B-
      and T-lymphocytes were negatively correlated with stroke severity at onset,
      including neurological deficits as assessed by National Institutes of Health
      Stroke Scale (NIHSS), and infarct volume as measured by the diffusion-weighted
      images (DWIs) of magnetic resonance (MR). Logistic regression analysis showed
      that modified Rankin scale (mRs) scores, a score system for the long-term
      neurological dysfunctions, were negatively correlated with the percentage of B
      lymphocytes at stroke onset. CONCLUSION: The proportions of B- and T-lymphocytes
      are associated with neurological outcomes of stroke patients and might be used as
      an indicator for severity and prognosis of ischemic stroke.

PMID- 29042781
TI  - Children with borderline intellectual functioning and autism spectrum disorder:
      developmental trajectories from 4 to 11 years of age.
AB  - BACKGROUND: Studies on autism have tended to focus either on those with
      intellectual disability (ie, those with intellectual quotient [IQ] under 70) or
      on the group that is referred to as "high-functioning", that is, those with
      borderline, average or above average IQ. The literature on cognition and daily
      functioning in autism spectrum disorder combined specifically with borderline
      intellectual functioning (IQ 70-84) is limited. METHODS: From a representative
      group of 208 preschool children diagnosed with autism spectrum disorder, those 50
      children in the group with borderline intellectual functioning at ages 4.5-6.5
      years were targeted for follow-up at a median age of 10 years. A new cognitive
      test was carried out in 30 children. Parents were interviewed with a semi
      structured interview together with the Vineland Adaptive Behavior Scales (n=41)
      and the Autism-Tics, attention-deficit/hyperactivity disorder (AD/HD) and other
      comorbidities inventory (A-TAC) (n=36). RESULTS: Most children of interviewed
      parents presented problems within several developmental areas. According to A-TAC
      and the clinical interview, there were high rates of attention deficits and
      difficulties with regulating activity level and impulsivity. Vineland Adaptive
      Behavior Scales composite scores showed that at school age, a majority of the
      children had declined since the previous assessment at ages between 4.5 and 6.5
      years. Almost half the tested group had shifted in their IQ level, to below 70 or
      above 84. CONCLUSION: None of the children assessed was without
      developmental/neuropsychiatric problems at school-age follow-up. The results
      support the need for comprehensive follow-up of educational, medical and
      developmental/neuropsychiatric needs, including a retesting of cognitive
      functions. There is also a need for continuing parent/family follow-up and
      support.

PMID- 29042782
TI  - Letter to the editor regarding the article "The use of Psychiatric
      Electroencephalography Evaluations Registry (PEER) to personalize
      pharmacotherapy".

PMID- 29042784
TI  - 19q12q13.2 duplication syndrome: neuropsychiatric long-term follow-up of a new
      case and literature update.
AB  - Genetic syndromes are well characterized by the phenotypic point of view, but
      little is known about their progression and patients' quality of life. We report
      a 10-year neuropsychiatric follow-up of a boy with duplication of chromosome 19.
      Cytogenetic investigation was requested at the age of 5 years for psychomotor and
      speech delay. The genomic study identified an 8.17 Mb duplication on chromosome
      19q12q13.2. We propose that the long-term follow-up of our patient would help to
      delineate the neuropsychiatric phenotype associated with 19q duplication. This
      study could be a model for further long-term research in the neuropsychiatric
      follow-up of patients with 19q duplication syndrome.

PMID- 29042783
TI  - Supplementation of omega 3 fatty acids may improve hyperactivity, lethargy, and
      stereotypy in children with autism spectrum disorders: a meta-analysis of
      randomized controlled trials.
AB  - AIM: Deficiency of omega 3 fatty acids may be linked to autism spectrum disorder
      (ASD). Evidence about the potential therapeutic effects of supplementation of
      omega 3 fatty acids is lacking in ASD patients. METHODS: We searched major
      electronic databases from inception to June 21, 2017, for randomized clinical
      trials, which compared treatment outcomes between supplementation of omega 3
      fatty acids and placebo in patients with ASD. An exploratory random-effects meta
      analysis of the included studies was undertaken. RESULTS AND CONCLUSION: Six
      trials were included (n=194). Meta-analysis showed that supplementation of omega
      3 fatty acids improved hyperactivity (difference in means =-2.692, 95% confidence
      interval [CI] =-5.364 to -0.020, P=0.048, studies =4, n=109), lethargy
      (difference in means =-1.969, 95% CI =-3.566 to -0.372, P=0.016, studies =4,
      n=109), and stereotypy (difference in means =-1.071, 95% CI =-2.114 to -0.029,
      P=0.044, studies =4, n=109). No significant differences emerged between
      supplementation of omega 3 fatty acids and placebo in global assessment of
      functioning (n=169) or social responsiveness (n=97). Our preliminary meta
      analysis suggests that supplementation of omega 3 fatty acids may improve
      hyperactivity, lethargy, and stereotypy in ASD patients. However, the number of
      studies was limited and the overall effects were small, precluding definitive
      conclusions. Future large-scale randomized clinical trials are needed to confirm
      or refute our findings.

PMID- 29042785
TI  - MLC601 in vascular dementia: an efficacy and safety pilot study.
AB  - BACKGROUND AND AIM: Vascular dementia (VaD) is the second most common cause of
      dementia and currently there is scarcity of therapies for VaD. We aimed to
      investigate the efficacy and safety of MLC601 in the treatment of VaD. METHODS:
      In this multicenter, pilot, randomized, double-blind trial, 82 patients with VaD
      according to DSM-5 criteria received MLC601 or placebo capsules three times a day
      for 2 years. The primary efficacy end-point was evaluated by comparing Mini
      Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale
      cognitive subscale (ADAS-cog) score between the two groups over 2 years of study.
      Safety was also assessed by recording adverse events and abnormal laboratory
      results. RESULTS: Eighty-one patients completed the study and were included in
      the analysis. One patient was lost to follow-up in the placebo group. After 2
      years, mean (+/-SD) changes in the MMSE score were -3.71 (+/-4.50) for MLC601
      group and -9.33 (+/-4.80) for placebo group. ADAS-cog score showed (+/-SD)
      changes of 7.34 (+/-9.55) and 19.00 (+/-11.28) for MLC601 and placebo group,
      respectively. Repeated measures analyses showed that both MMSE and ADAS-cog
      scores were significantly better in the treatment group at 24 months (p<0.001).
      Ten (24.39%) patients reported predominantly transient gastrointestinal adverse
      events in MLC601 group. No patient left the study due to adverse events. There
      were no clinically significant abnormalities on laboratory tests. CONCLUSION:
      Patients treated with MLC601 over the 2 years showed dramatically better
      cognitive outcome compared with those treated with placebo. MLC601 was devoid of
      any serious adverse events and was well-tolerated.

PMID- 29042786
TI  - Interpersonal sensitivity mediates the effects of child abuse and affective
      temperaments on depressive symptoms in the general adult population.
AB  - BACKGROUND: Recent studies have suggested that multiple factors interact with the
      onset and prognosis of major depressive disorders. In this study, we investigated
      how child abuse, affective temperaments, and interpersonal sensitivity are
      interrelated, and how they affect depressive symptoms in the general adult
      population. SUBJECTS AND METHODS: A total of 415 volunteers from the general
      adult population completed the Patient Health Questionnaire-9, the Temperament
      Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire version, the
      Child Abuse and Trauma Scale, and the Interpersonal Sensitivity Measure, which
      are all self-administered questionnaires. Data were subjected to structural
      equation modeling (Mplus), and single and multiple regression analyses. RESULTS:
      The effect of child abuse on depressive symptoms was mediated by interpersonal
      sensitivity and 4 affective temperaments, including depressive, cyclothymic,
      anxious, and irritable temperaments. In addition, the effect of these
      temperaments on depressive symptoms was mediated by interpersonal sensitivity,
      indicating the indirect enhancement of depressive symptoms. In contrast to these
      4 temperaments, the hyperthymic temperament did not mediate the effect of child
      abuse on depressive symptoms; its effect was not mediated by interpersonal
      sensitivity. However, a greater hyperthymic temperament predicted decreased
      depressive symptoms and interpersonal sensitivity, independent of any mediation
      effect. LIMITATIONS: Because this is a cross-sectional study, long-term
      prospective studies are necessary to confirm its findings. Therefore, recall bias
      should be considered when interpreting the results. As the subjects were adults
      from the general population, the results may not be generalizable towards all
      patients with major depression. CONCLUSION: This study suggests that child abuse
      and affective temperaments affect depressive symptoms partly through
      interpersonal sensitivity. Interpersonal sensitivity may have a major role in
      forming the link between abuse, affective temperament, and depression.

PMID- 29042787
TI  - Perinatal and follow-up outcome study of fetal anomalies with multidisciplinary
      consultation.
AB  - SYNOPSIS: The establishment of a multidisciplinary consultation system is
      necessary for the diagnosis of complicated fetal anomalies. PURPOSE: We aimed to
      investigate the incidences of different types of fetal anomalies and the
      influence of multidisciplinary consultation on fetal prognosis. PATIENTS AND
      METHODS: Multidisciplinary specialists include obstetricians, pediatricians,
      pediatric surgeons, and experts of ultrasound department and genetic counseling.
      Consultation was done if the fetal ultrasound examinations showed abnormality.
      Follow-up, assistance, and guidance for the fetus were achieved by phone calls.
      RESULTS: Ultrasound screening showed that the incidences of central nervous
      system anomaly and genitourinary anomaly were 25.80% (275/1,066) and 22.05%
      (235/1,066), respectively. The detection rates of fetal anomalies were 5.07%
      (54/1,066), 36.12% (385/1,066), and 58.82% (627/1,066) in pregnant women with
      gestational age of <20, 20-28, and >28 weeks, respectively. In addition, the
      fetal cerebral ventriculomegaly accounted for 40.73% of central nervous system
      malformation, while 71.43% cases with fetal cerebral ventriculomegaly were
      alleviated during the follow-up period. The proportion of hydronephrosis in
      genitourinary anomalies was 50.64%, and the remission rate of hydronephrosis was
      67.23% during the follow-up period. CONCLUSION: The establishment of a
      multidisciplinary consultation system is necessary for the diagnosis of
      complicated fetal anomalies. The central nervous system anomaly and genitourinary
      anomaly are the most common fetal anomalies. In addition, the remission rates of
      cerebral ventriculomegaly and fetal hydronephrosis are high during the follow-up
      period.

PMID- 29042789
TI  - Linked-color imaging combined with the NICE classification system for optical
      diagnosis of colon polyps: new image-enhanced endoscopic technology for
      pathological prediction.
AB  - INTRODUCTION: Linked-color imaging (LCI) is a recently developed system used in
      endoscopy. It creates clear and bright endoscopic images using short-wavelength,
      narrow-band laser light combined with white laser light. The illuminating light
      and signal processing emphasize slight color differences in abnormal regions that
      approximate the normal color of the mucosa. As a result, regions initially
      appearing red become a deeper shade of red, while regions originally appearing
      white become brighter, yet with natural tones. This process facilitates
      recognition of slight differences in the color of the mucosa and clarifies the
      boundaries of the mucosal pit. AIM: To determine whether LCI of the colon can
      improve the correlation between endoscopic findings and pathological diagnosis.
      METHODS: Consecutive patients who underwent colonoscopy requiring polypectomy or
      removal by biopsy forceps if possible were recruited. Probable polyp histology
      was assessed by two endoscopists using the Narrow-band imaging International
      Colorectal Endoscopic (NICE) classification and LCI data. All detected polyps
      were sent to the pathology department for pathological diagnosis by two
      pathologists. RESULTS: In total, 94 polyps were found in 43 patients. The
      sensitivity, specificity, positive predictive value, and negative predictive
      value for neoplastic lesion prediction (NICE type2/3) were 96.5%, 83.8%, 90.2%,
      and 93.9%, respectively. CONCLUSION: LCI combined with the NICE classification
      system is a powerful tool for predicting probable histology of colon polyps.

PMID- 29042788
TI  - Decreased frequency of adenoidectomy by a 12-week nasal budesonide treatment.
AB  - OBJECTIVE: There is little evidence on the role of topical budesonide in reducing
      the frequency of adenoidectomy, although it was reported that topical budesonide
      can effectively ameliorate the symptoms of adenoid hypertrophy (AH). This study
      was aimed to investigate the possibility and safety of alternatives to
      adenoidectomy with a 12-week treatment with nasal budesonide. MATERIALS AND
      METHODS: One hundred patients with AH were randomized to receive either a double
      blind budesonide (1 mg once daily) or placebo treatment for 2 weeks by transnasal
      nebulization. A further 12-week open study, budesonide spray (64 MUg per nostril
      at bedtime) was administered to the treatment group. During the final 12 weeks of
      follow-up, the frequency of adenotonsillectomy, side effects, the degree of nasal
      obstruction, nasal discharge, and snoring were assessed. RESULTS: Out of the 100
      total enrolled patients, 92 children with AH completed the study. After the 2
      week treatment with transnasal budesonide nebulization, the symptoms of AH
      significantly decreased compared to the control group. Responders (n=26) who had
      initially improved showed significantly decreased symptoms of AH, and the
      frequency of adenotonsillectomy during the follow-up (14 and 26 weeks) was
      compared with that of the control group and non-responders (n=21) who did not
      respond to the initial 2-week budesonide therapy. The 12-week nasal budesonide
      treatment did not suppress the growth rate of children's height or cause other
      side effects. CONCLUSION: AH children who had improved after an initial 2-week
      budesonide therapy can achieve clinical improvements and decreased frequency of
      adenoidectomy following the therapy with a 12-week treatment with nasal
      budesonide.

PMID- 29042790
TI  - Evaluation of vitamin D levels in relation to coronary CT angiographic findings
      in an Iranian population.
AB  - BACKGROUND: Vitamin D deficiency, as a predisposing factor for coronary artery
      disease (CAD), is a subject of increasing interest. However, its role as a risk
      factor has not been proven. This study aimed to investigate the relationship
      between serum vitamin D levels and CAD. MATERIALS AND METHODS: Using a cross
      sectional design, 180 patients who were candidates for coronary computed
      tomography angiography (CCTA) were selected. Serum levels of vitamin D were
      measured and compared with the results of CCTA (including calcium score, and
      presence and severity of coronary artery involvement due to atherosclerotic
      plaques). RESULTS: The mean age of the participants was 60.5+/-10.6 years and the
      mean serum vitamin D level was 26.2+/-15.9 ng/dL (range, 3.5-83.2 ng/dL).
      Overall, 6.1% of the participants (n=11) had vitamin D deficiency, 56.1% (n=101)
      had insufficient levels of vitamin D, and 37.8% (n=68) had sufficient levels of
      vitamin D. The mean serum vitamin D level was significantly lower in patients
      with severe CAD (P=0.004). The serum vitamin D level in the "positive for CAD"
      group was 20.98 ng/mL, significantly lower than the level in the "negative for
      CAD" group (30.47 ng/mL; P<0.001). The mean calcium score among participants was
      533.5+/-87.9. Based on the Spearman test, a significant negative correlation (
      0.21) was detected between the serum vitamin D level and coronary artery calcium
      score (CACS) (P=0.005). Conversely, the mean CACS in the vitamin D deficient
      group was significantly higher than in the insufficient and sufficient vitamin D
      groups (P<0.001 for both comparisons). CONCLUSION: Vitamin D deficiency was
      associated with coronary artery calcification and severity of coronary artery
      stenosis in Iranian patients.

PMID- 29042791
TI  - Profile of sacubitril/valsartan in the treatment of heart failure: patient
      selection and perspectives.
AB  - With an estimated prevalence of 5.8 million in the USA and over 23 million people
      worldwide, heart failure (HF) is growing in epidemic proportions. Despite the use
      of guideline-directed medical therapies such as angiotensin-converting enzyme
      inhibitors, beta-adrenergic blockers, angiotensin receptor blockers, and
      mineralocorticoid receptor antagonists for chronic systolic HF for almost two
      decades, HF remains a leading cause of morbidity, mortality, and health care
      expenditures. The Prospective Comparison of Angiotensin Receptor-Neprilysin
      Inhibitor with Angiotensin-Converting Enzyme Inhibitor to Determine Impact on
      Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial provided
      compelling evidence for the cardiovascular and mortality benefit of
      sacubitril/valsartan when compared to enalapril in patients with heart failure
      and reduced ejection fraction (HFrEF). Sacubitril/valsartan performed better than
      enalapril across various HFrEF patient characteristics and showed substantial
      benefit in patients with other common comorbidities. Following the trial, the US
      Food and Drug Administration approved this drug for the treatment of HF. Various
      international HF consensus guidelines endorse sacubitril/valsartan as a class I
      recommendation for the management of symptomatic HFrEF. Although this high
      quality clinical study is the largest and the most globally represented trial in
      HFrEF patients, concerns have been raised regarding the generalizability of the
      trial results in real-world HF population. The gaps in US Food and Drug
      Administration labeling and guideline recommendations might lead to this
      medication being used in a larger population than it was studied in. In this
      review, we will discuss the current role of sacubitril/valsartan in the
      management of HF, concerns related to PARADIGM-HF and answers, shortcomings of
      this novel drug, effects on patient characteristics, real-world eligibility, and
      the role of ongoing and further investigations to clarify the profile of
      sacubitril/valsartan in the management of HF.

PMID- 29042792
TI  - Low dose of kaempferol suppresses the migration and invasion of triple-negative
      breast cancer cells by downregulating the activities of RhoA and Rac1.
AB  - PURPOSE: Triple-negative breast cancer (TNBC) is an especially aggressive and
      hard-to-treat disease. Although the anticancer role of kaempferol has been
      reported in breast cancer, the effect of kaempferol on TNBC remains unclear.
      MATERIALS AND METHODS: This experiment investigated the migration-suppressive
      role of a low dose of kaempferol in TNBC cells. Wound-healing assays and cell
      invasion assays were used to confirm the migration and invasion of cells treated
      with kaempferol or transfected indicated constructs. We evaluated the activations
      of RhoA, Rac1 and Cdc42 in TNBC cells with a Rho activation assay. A panel of
      inhibitors of estrogen receptor/progesterone receptor/human epidermal growth
      factor receptor 2 (ER/PR/HER2) treated non-TNBC (SK-BR-3 and MCF-7) cells and
      blocked the ER/PR/HER2 activity. Wound-healing assays and Rho activation assays
      were employed to measure the effect of kaempferol and ER/PR/HER2 inhibitors on
      Rho activation and cell migration rates. RESULTS: A low dose of kaempferol (20
      MUmol/L) had a potent inhibitory effect on the migration and invasion of TNBC
      cells, but not on the migration of non-TNBC (SK-BR-3 and MCF-7) cells. The low
      dose of kaempferol downregulated the activations of RhoA and Rac1 in TNBC cells.
      Moreover, the low dose of kaempferol also inhibited the migration and RhoA
      activations of HER2-silence SK-BR-3 and ER/PR-silence MCF-7 cells. Overexpressed
      HER2 rescued the cell migration and RhoA and Rac1 activations of kaempferol
      treated MDA-MB-231 cells. CONCLUSION: The low dose of kaempferol inhibits the
      migration and invasion of TNBC cells via blocking RhoA and Rac1 signaling
      pathway.

PMID- 29042793
TI  - Theranostics in nuclear medicine practice.
AB  - The importance of personalized medicine has been growing, mainly due to a more
      urgent need to avoid unnecessary and expensive treatments. In nuclear medicine,
      the theranostic approach is an established tool for specific molecular targeting,
      both for diagnostics and therapy. The visualization of potential targets can help
      predict if a patient will benefit from a particular treatment. Thanks to the
      quick development of radiopharmaceuticals and diagnostic techniques, the use of
      theranostic agents has been continually increasing. In this article, important
      milestones of nuclear therapies and diagnostics in the context of theranostics
      are highlighted. It begins with a well-known radioiodine therapy in patients with
      thyroid cancer and then progresses through various approaches for the treatment
      of advanced cancer with targeted therapies. The aim of this review was to provide
      a summary of background knowledge and current applications, and to identify the
      advantages of targeted therapies and imaging in nuclear medicine practices.

PMID- 29042794
TI  - Comparison of microwave ablation and hepatic resection for hepatocellular
      carcinoma: a meta-analysis.
AB  - BACKGROUND AND AIMS: Hepatic resection (HRN) and microwave ablation (MWA) have
      significant advantages in treating hepatocellular carcinoma; however, it remains
      unclear which way produces better outcomes. This meta-analysis of cohort studies
      compared the treatments in terms of effectiveness and safety. METHODS: Six
      electronic databases (PubMed, Medline, EMBASE, Web of Science, EBSCO, and The
      Cochrane Library) were retrieved for studies comparing MWA and HRN. The meta
      analysis was conducted based on statement of preferred reporting items for
      systematic reviews and meta-analyses. RESULTS: Nine studies met the inclusion
      criteria, with a total of 1,480 patients. The overall meta-analysis demonstrated
      no significant difference in overall survival between the MWA group and the HRN
      group (HR =0.98, 95% CI =0.76-1.26, P=0.878). There was no difference in disease
      free survival between the MWA group and the HRN group (HR =1.16, 95% CI =0.79
      1.71, P=0.442). Meanwhile, the meta-analysis demonstrated that MWA was associated
      with shorter operation time (standardized mean difference [SMD] =-1.37, 95% CI =
      1.92 to -0.81, P=0.000), less amount of blood loss in operation (SWD =-1.19, 95%
      CI =-1.76 to -0.61, P=0.000), and less complications (OR =0.22, 95% CI =0.12
      0.40, P=0.000) than HRN. CONCLUSION: In conclusion, our meta-analysis suggests
      that MWA may be superior to HRN as it is as effective as HRN in terms of overall
      survival, disease-free survival, tumor recurrence, and is associated with shorter
      operation time, less amount of blood loss, and fewer complications.

PMID- 29042795
TI  - Significant association of the EXO1 rs851797 polymorphism with clinical outcome
      of ovarian cancer.
AB  - BACKGROUND: Exonuclease 1 (EXO1), one of DNA mismatch repair pathway genes,
      functions in maintaining genomic stability and affects tumor progression. We
      hypothesized that genetic variations in EXO1 may predict clinical outcomes in
      epithelial ovarian cancer (EOC). METHODS: In this cohort study with 1,030
      consecutive EOC patients, we genotyped four potentially functional polymorphisms
      in EXO1 by the Taqman assay and evaluated their associations with patients'
      survival. RESULTS: Using multivariate Cox proportional hazards regression models,
      we found that rs851797AG/GG genotypes were significantly associated with
      recurrence and cancer death (HR =1.30 and 1.38, 95% CI =1.11-1.52 and 1.02-1.88,
      respectively). Kaplan-Meier survival estimates showed that patients who carried
      rs851797AG/GG genotypes had poorer progression-free survival and poorer overall
      survival, compared with rs851797AA genotype carriers (log-rank test, P=0.002 and
      0.025, respectively). Moreover, patients with older age at menophania, advanced
      stage tumor, or being received incomplete cytoreduction were more likely to be
      recurrent and dead. CONCLUSION: EXO1 rs851797 polymorphism can predict the
      clinical outcomes in EOC patients. In addition, age at menophania, FIGO stage,
      and complete cytoreduction might be independently prognostic factors of ovarian
      cancer. Large studies with functional experiments are warranted to validate these
      findings.

PMID- 29042796
TI  - TERT-CLPTM1 locus polymorphism (rs401681) is associated with the prognosis of
      hepatocellular carcinoma.
AB  - Telomere length is associated with the development of hepatocellular carcinoma
      (HCC), and recent studies have focused on the genetic alteration or polymorphism
      in telomere-maintaining genes. We examined the clinicopathologic and prognostic
      value of rs401681 polymorphism, located in the TERT-CLPTM1L locus, in HCC. The
      relationship between rs401681 variants and telomere length was also analyzed in
      156 HCC patients. The rs401681 polymorphism had the following genotype
      frequencies: C/C in 51.3% of the samples, C/T in 39.7%, and T/T in 9.0%.
      Telomeres in the tumor samples were 4.04-fold longer, on average, than the
      telomeres in matched normal samples (SD =1.32), and there were no differences in
      telomere length according to rs401681 polymorphism (p=0.802). Our results
      indicate that the rs401681 C allele was significantly associated with increased T
      and International Union for Cancer Control stages (p<0.01). Univariate and
      multivariate survival analyses showed that HCC with C allele had poorer prognosis
      (p<0.01). In conclusion, our findings suggest that rs401681 is a possible
      prognostic biomarker for HCC patients.

PMID- 29042797
TI  - ER-positive breast cancer patients with more than three positive nodes or grade 3
      tumors are at high risk of late recurrence after 5-year adjuvant endocrine
      therapy.
AB  - PURPOSE: Currently, although several clinical trials available give strong
      suggestions that extension of endocrine therapy has benefits, the risk level at
      which patients may benefit from extended endocrine therapy remains uncertain.
      This study aimed to identify the proportion of patients at a substantial risk of
      late recurrence after 5-year adjuvant endocrine therapy. PATIENTS AND METHODS: We
      reviewed 1,056 female patients with primary breast cancer who underwent curative
      resection between January 2006 and December 2011. Univariate and multivariate
      analyses were performed using the Cox proportional hazards regression model to
      identify prognostic factors. RESULTS: A total of 327 eligible patients were
      eventually enrolled in this study. Among them, 42 (12.8%) patients suffered from
      distant metastasis and 34 (10.4%) patients experienced locoregional recurrence
      after 5-year adjuvant endocrine therapy. In multivariate analysis, patients with
      more than three positive nodes (hazard ratio [HR] =2.176, 95% CI=1.071-4.421;
      P=0.032) and histologic grade 3 disease (HR=2.098, 95% CI=1.300-3.385; P=0.002)
      were significantly associated with high risk of late recurrence. However, only
      histologic grade 3 (HR=2.212, 95% CI=1.166-4.194; P=0.015) was significantly
      associated with high risk of distant metastasis. CONCLUSION: Late relapse after
      completion of 5-year adjuvant endocrine therapy was still common, and grade 3 and
      more than three positive nodes were the risk factors of late recurrence, while
      grade 3 was the only risk factor of late distant metastasis. These patients might
      benefit from extended endocrine therapy.

PMID- 29042798
TI  - Crizotinib, a MET inhibitor, inhibits growth, migration, and invasion of breast
      cancer cells in vitro and synergizes with chemotherapeutic agents.
AB  - MET is a receptor tyrosine kinase known for its pleiotropic effects in
      tumorigenesis. Dysregulations of MET expression and/or signaling have been
      reported and determined to be associated with inferior outcomes in breast cancer
      patients rendering MET a versatile candidate for targeted therapeutic
      intervention. Crizotinib is a multi-targeted small-molecule kinase inhibitor for
      MET, ALK, and ROS1 kinases. This study evaluated the anti-proliferative,
      cytotoxic, anti-migratory, and anti-invasive effects of crizotinib in breast
      cancer cells in vitro. Cell viability was assessed by 3-(4,5-dimethyl-2
      thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) colorimetric assay. In vitro
      wound-healing assay was used to examine the effect of crizotinib on breast cancer
      cell migration. The expressions of Ki-67, MET, and phospho-MET receptors were
      characterized using immunofluorescence staining. Results showed that crizotinib
      has significant anti-proliferative activity on all mammary tumor cells with IC50
      values of 5.16, 1.5, and 3.85 uM in MDA-MB-231, MCF-7, and SK-BR-3 cells,
      respectively. Crizotinib induced cytotoxic effects in all breast cancer cells
      examined. Combined treatment of small dose of crizotinib with paclitaxel or
      doxorubicin exhibited a highly synergistic inhibition of growth of MDA-MB-231 and
      MCF-7 cells with combination index values <1 while no significant effect was
      observed in SK-BR-3 cells compared with individual compounds. Treatment with
      crizotinib demonstrated a remarkable reduction in the expression of Ki-67 protein
      in all 3 tested cell lines. Crizotinib inhibited migration and invasion of MDA-MB
      231 cells in a dose-dependent fashion. Crizotinib reduced MET receptor activation
      in MDA-MB-231 cells when treated at effective concentrations. In conclusion,
      crizotinib suppressed proliferation, migration, and invasion of breast cancer
      cells in vitro. The results of this study demonstrated that combined treatment of
      crizotinib with chemotherapeutic agents resulted in a synergistic growth
      inhibition of specific breast cancer cell lines.

PMID- 29042799
TI  - Asthma symptoms, mannitol reactivity and exercise-induced bronchoconstriction in
      adolescent swimmers versus tennis players.
AB  - BACKGROUND: Strenuous physical activity at an elite level is associated with an
      increased risk for asthma and, in some sports, also prevalence of allergies. The
      aim of this study was to investigate the prevalence of asthma and allergy among
      elite swimmers and tennis players and compare airway hyperreactivity to mannitol
      and exercise. MATERIALS AND METHODS: One hundred and one adolescent swimmers and
      86 tennis players answered a questionnaire about respiratory symptoms and allergy
      and performed mannitol challenge and sport-specific exercise challenge. Atopy was
      assessed and fractional exhaled nitric oxide was measured. Mannitol positivity
      was defined as drop in FEV1 >=15% (ordinary criteria) and/or beta2-reversibility
      (>=15%) after provocation (extended criteria). A positive exercise test was
      defined as a drop in FEV1 >=10% (ordinary criteria) and/or beta2-reversibility
      (>=15%) after provocation (extended criteria). Club cell protein (CC16) was
      measured in urine before and after the challenges. RESULTS: Asthma symptoms were
      common in both groups. More swimmers had exercise-induced symptoms (77% versus
      50%) and current asthma symptoms (56% versus 38%), compared to the tennis
      players. More swimmers also had a positive mannitol challenge test both using
      ordinary (26% versus 6%) and extended criteria (43% versus 17%), while the number
      of positive exercise tests did not differ. After exercise (but not mannitol)
      challenge, CC16 level was increased in both groups, but to a higher extent in
      tennis players. There were no differences in atopy, rhinitis or fractional
      exhaled nitric oxide. CONCLUSION: We found a high prevalence of asthma among
      elite swimmers and tennis players and a higher frequency of current asthma and
      positive mannitol challenge tests among the swimmers. This indicates an
      unfavorable exercise environment.

PMID- 29042800
TI  - Postpartum airway responsiveness and exacerbation of asthma during pregnancy - a
      pilot study.
AB  - BACKGROUND: Airway responsiveness and inflammation are associated with the
      clinical manifestations of asthma and the response to pharmacological therapy.
      OBJECTIVE: To investigate if airway responsiveness and inflammatory
      characteristics are related to asthma exacerbations during pregnancy. MATERIALS
      AND METHODS: In women with asthma who were prescribed controller medication and
      monitored closely during pregnancy, the risk of exacerbations was analyzed in
      relation to postpartum measures of fractional exhaled nitric oxide (FENO), skin
      prick test reactivity, static and dynamic lung volumes, diffusing capacity for
      carbon monoxide, bronchial responsiveness to inhaled mannitol, and inflammatory
      characteristics in induced sputum. Obtained data were analyzed in relation to
      exacerbation status during pregnancy. The PD15 is defined as the cumulative
      administered dose causing a 15% decline in forced expiratory volume in the first
      second (FEV1). RESULTS: Fifty women (mean age +/- standard deviation of 32+/-5
      years) were enrolled over an 11-month period and examined on average 4 months
      postpartum. During pregnancy, 13 women had a total of 16 exacerbations (8 mild
      and 8 severe). Women with asthma exacerbation during pregnancy had more
      pronounced airway responsiveness to inhaled mannitol (geometric mean PD15 82 vs
      171 mg, p=0.04) and were less likely to be atopic (62% vs 86%, respectively;
      p=0.04) than the non-exacerbators. No statistically significant difference was
      found between the 2 groups of women with regard to type of airway inflammation in
      sputum and fractional exhaled nitric oxide (FENO). CONCLUSION: More pronounced
      airway hyperresponsiveness together with nonatopic status appears to characterize
      women at high risk of exacerbation of asthma during pregnancy.

PMID- 29042801
TI  - Investigating a rare methicillin-resistant Staphylococcus aureus strain: first
      description of genome sequencing and molecular characterization of CC15-MRSA.
AB  - PURPOSE: Methicillin resistant Staphylococcus aureus CC15 strains (CC15-MRSA)
      have only been sporadically described in literature. This study was carried out
      to describe the genetic make-up for this rare MRSA strain. METHODS: Four CC15
      MRSA isolates collected in Riyadh, Saudi Arabia, between 2013 and 2014 were
      studied. Two isolates were from clinical infection and 2 from retail meat
      products. Whole genome sequencing was carried out using Illumina HiSeq2500 genome
      analyzer. RESULTS: All the CC15-MRSA isolates had the multilocus sequence typing
      profile ST1535, 13-13-1-1-81-11-13, which is a single locus variant of ST15. Of
      the 6 contigs related to the SCC element, one comprised a recombinase gene ccrAA,
      ccrC-PM1, fusC and a helicase, another one included mvaS, dru, mecA and 1 had
      yobV and Q4LAG7. The SCC element had 5 transposase genes, namely 3 identical
      paralogs of tnpIS431 and 2 identical paralogs of tnpIS256. Two identical copies
      of a tnpIS256-based insertion element flank the aacA-aphD gene. Two copies of
      this insertion element were present with 1 located in the SCC element and another
      inserted into the sasC gene. A short 3 kb region, which lacks any bacteriophage
      structural genes and site-specific DNA integrase, was inserted into the hlb gene.
      The hsdM and the 5'-part of the hsdS gene are replaced by a copy of the hsdM/hsdS
      paralogs from nuSabeta giving rise to a new chimeric paralog of hsdS in
      nuSaalpha. CONCLUSION: CC15-MRSA shows a novel SCCmecV/SCCfus composite element.
      Its variant of hsdM/hsdS probably facilitated uptake of foreign mobile genetic
      elements that promoted emergence of CC15-MRSA. Close surveillance is needed to
      monitor spread and emergence of further CC15 MRSA strains.

PMID- 29042802
TI  - Utilization of fetal fibronectin testing and pregnancy outcomes among women with
      symptoms of preterm labor.
AB  - OBJECTIVES: To identify pregnant health plan members triaged through the
      emergency department (ED), including labor and delivery (ELD) units, with
      symptoms of preterm labor (PTL), and evaluate the use of fetal fibronectin (fFN)
      testing; and to calculate the rate of hospitalization and timing of delivery in
      relation to the ED visit. METHODS: Retrospective cohort study using Medical
      Outcomes Research for Effectiveness and Economics Registry(r), a national
      multipayer claims database. A cohort of pregnant women evaluated in an ELD with a
      diagnosis of PTL from June 2012 through November 2015 was identified. The
      proportion of women with PTL who received fFN testing was calculated. RESULTS: A
      total of 23,062 patients met the criteria for inclusion in the study. The rate of
      fFN testing prior to delivery was 12.0%. Of the 23,062 patients included in the
      analysis, 75.9% were discharged home. Of those who were discharged from the
      emergency room, one in five went on to deliver within 3 days and almost 96% of
      this group was not screened for the presence of fFN. Of the remaining 24.1% of
      patients admitted to the hospital, 91.3% delivered during their stay. In a
      sensitivity analysis, the percentage of women who delivered within 3 days of the
      ELD encounter was lower for women who received fFN testing only (6.6%) versus
      those who had a history of transvaginal ultrasound (TVUS) only (21.6%).
      Furthermore, the rate of delivery within 3 days was lowest among patients who had
      both fFN testing and TVUS (4.7%). CONCLUSION: The utilization of fFN testing is
      12%. The majority of pregnant patients triaged through the ELD with symptomatic
      PTL do not receive an fFN test. As part of PTL evaluation, fFN testing may
      identify women at increased risk for preterm delivery and help determine
      appropriate patient management.

PMID- 29042803
TI  - The cost of successful antiviral therapy in hepatitis C patients: a comparison of
      IFN-free versus IFN-based regimens at an individual patient level in Australia.
AB  - BACKGROUND: Chronic hepatitis C remains a major global health burden with serious
      long-term consequences if left untreated. Recently the treatment standard of care
      has shifted to new interferon (IFN)-free drug regimens, which have been shown to
      be safe and effective. The aim of our study was to assess and compare medical
      resource utilization and costs of successfully treating patients with IFN-based
      and IFN-free therapies in Australia. METHODS: We performed a retrospective chart
      review of 30 HCV-infected patients successfully treated with IFN-based therapy
      between 2013 and 2015. We also generated a model for a virtual group of 100
      genotype 1 (GT1) and 100 genotype 3 (GT3) patients treated with IFN-free therapy
      derived from national guidelines and clinical trial data. RESULTS: In comparison
      to virtual patients receiving IFN-free therapy, our IFN-treated patients on
      average had distinctively more liver clinic visits and blood tests. However, mean
      total cost per patient was $19,164 and $85,300 (AUD) more for GT1 and GT3
      patients receiving IFN-free therapy, respectively. This difference was largely
      accounted for by higher antiviral drug costs. Of our 30 patients treated with
      IFN, total mean cost per patient during the study period was $33,595. CONCLUSION:
      Resource utilization is lower with IFN-free treatment, which reflects the reduced
      need for patient monitoring and improved side-effect profile of these new drugs.
      However, total costs are still largely dominated by antiviral drug costs,
      representing a huge burden on national budgets. Our insight into resource
      utilization and costs associated with both types of treatment can serve as a
      reference for future studies.

PMID- 29042804
TI  - Weight loss medications in Canada - a new frontier or a repeat of past mistakes?
AB  - Current methods for the treatment of excess weight can involve healthy behavior
      changes, pharmacotherapy, and surgical interventions. Many individuals are able
      to lose some degree of weight through behavioral changes; however, they are often
      unable to maintain their weight loss long-term. This is in part due to
      physiological processes that cannot be addressed through behavioral changes
      alone. Bariatric surgery, which is the most successful treatment for excess
      weight to date, does result in physiological changes that can help with weight
      loss and weight maintenance. However, many patients either do not qualify or
      elect to not have this procedure. Fortunately, research has recently identified
      changes in neurochemicals (i.e., orexigens and anorexigens) that occur during
      weight loss and contribute to weight regain. The neurochemicals and hormones may
      be able to be targeted by medications to achieve greater and more sustained
      weight loss. Two medications are approved in adjunction to lifestyle management
      for weight loss in Canada: orlistat and liraglutide. Both medications are able to
      target physiological processes to help patients lose weight and maintain a
      greater amount of weight loss than with just behavioral modifications alone. Two
      other weight management medications, which also target specific physiological
      processes to aid in weight loss and its maintenance, a bupropion/naltrexone
      combination and lorcaserin, are currently pending approval in Canada.
      Nonetheless, there remain significant barriers for health care professionals to
      prescribe medications for weight loss, such as a lack of training and knowledge
      in the area of obesity. Until this has been addressed, and we begin treating
      obesity as we do other diseases, we are unlikely to combat the increasing trend
      of obesity in Canada and worldwide.

PMID- 29042805
TI  - Efficacy of the combined use of a mild foaming cleanser and moisturizer for the
      care of infant skin.
AB  - OBJECTIVE: Despite the application of skin care treatments, many infants have
      skin problems such as dryness and erythema. We proposed a new combination skin
      care for infants which consisted of a foaming cleanser with lower surfactant
      activity and moisturizers that contained pseudo-ceramide. SUBJECTS AND METHODS: A
      total of 50 infants (age: 3-24 months) with insignificant levels of dry skin were
      enrolled in this usage trial. The parents washed the infants with the test
      cleanser while bathing and then applied the moisturizer (lotion or cream)
      containing pseudo-ceramide. Prior to and following the 4-week usage period,
      visual evaluation of the skin condition was conducted by a dermatologist, in
      addition to instrumental analysis. RESULTS: Erythema and papule, accompanied by
      dryness, were commonly observed at week 0. However, by week 4, these symptoms
      significantly improved; the condition of none of the subjects deteriorated. The
      number of infants with lower cutaneous barrier function and higher skin pH
      decreased. The parents of the infants recognized improvements in the skin
      symptoms and were appreciative of the test materials. CONCLUSION: The combined
      usage of the foaming cleanser with lower surfactant activity and a moisturizer
      containing pseudo-ceramide may be effective in maintaining healthy infant skin
      and ameliorating the skin symptoms.

PMID- 29042806
TI  - Feeding filaggrin: effects of l-histidine supplementation in atopic dermatitis.
AB  - Atopic dermatitis (AD), also known as eczema, is one of the most common chronic
      skin conditions worldwide, affecting up to 16% of children and 10% of adults. It
      is incurable and has significant psychosocial and economic impacts on the
      affected individuals. AD etiology has been linked to deficiencies in the skin
      barrier protein, filaggrin. In mammalian skin, l-histidine is rapidly
      incorporated into filaggrin. Subsequent filaggrin proteolysis releases l
      histidine as an important natural moisturizing factor (NMF). In vitro studies
      were conducted to investigate the influence of l-histidine on filaggrin
      processing and barrier function in human skin-equivalent models. Our further aim
      was to examine the effects of daily oral l-histidine supplementation on disease
      severity in adult AD patients. We conducted a randomized, double-blind, placebo
      controlled, crossover, nutritional supplementation pilot study to explore the
      effects of oral l-histidine in adult AD patients (n=24). In vitro studies
      demonstrated that l-histidine significantly increased both filaggrin formation
      and skin barrier function (P<0.01, respectively). Data from the clinical study
      indicated that once daily oral l-histidine significantly reduced (P<0.003) AD
      disease severity by 34% (physician assessment using the SCORingAD tool) and 39%
      (patient self-assessment using the Patient Oriented Eczema Measure tool) after 4
      weeks of treatment. No improvement was noted with the placebo (P>0.32). The
      clinical effect of oral l-histidine in AD was similar to that of mid-potency
      topical corticosteroids and combined with its safety profile suggests that it may
      be a safe, nonsteroidal approach suitable for long-term use in skin conditions
      that are associated with filaggrin deficits such as AD.

PMID- 29042807
TI  - Association between interleukin-6/6R gene polymorphisms and coronary artery
      disease in Russian population: influence of interleukin-6/6R gene polymorphisms
      on inflammatory markers.
AB  - This study determined the genotype effects of interleukin (IL)-6/IL-6R single
      nucleotide polymorphisms (SNPs) on circulating levels of different cytokines in
      healthy and coronary artery disease (CAD) patients with different allele
      frequencies. In the control patients, rs1800795 showed significant differences in
      IL-18 concentrations between CC and CG and CC and GG genotypes (P=0.003 and
      0.004, respectively). Furthermore, circulatory IL-1beta was significantly
      different between GC and GG genotypes from the same SNP (P=0.038). In the
      diseased patients, significance was determined only for IL-2 (P=0.021) between
      the C and G homozygote allele carriers of rs1800795. The diseased GC and GG
      genotype carriers were statistically different for IL-2 (P=0.049) from the
      rs1800796 and for IL-4 (P=0.049) from the rs2228044. IL-4 was also statistically
      significant between the GC and CC genotypes from the rs2228043 of the IL-6R gene
      (P=0.025). The last combination of genotypes in the same gene for the same SNP
      was statistically significant for IL-10 (P=0.036). According to the logistic
      regression, only gender (odds ratio [OR] =2.43) and triglycerides (OR =1.98)
      could be taken as determinants of CAD, while examined SNPs genotypes were not
      identified as risk factors for CAD. In general, the IL-6 polymorphism genotypes
      were mainly associated with inflammatory cytokines, while the IL-6R polymorphism
      genotypes were associated with anti-inflammatory cytokines.

PMID- 29042808
TI  - First-visit patients without a referral to the Department of Internal Medicine at
      a medium-sized acute care hospital in Japan: an observational study.
AB  - PURPOSE: We sought to profile first-time patients without a referral who sought
      medical care at the Department of Internal Medicine at a medium-sized acute care
      hospital in Japan. We anticipated that the analysis would highlight the demand
      for medical care needs from acute care hospitals and help confirm one of the
      problems associated with primary care in Japan. PATIENTS AND METHODS: The study
      population comprised 765 patients who sought outpatient consultation without a
      referral at "the Department of General Internal Medicine" at the Ikeda City
      Hospital on Fridays over 4 years. Data on the following variables were collected:
      age, sex, examination date, reason for encounter (RFE), diagnosis, as well as
      history of consultation with or without antibiotic treatment at another medical
      institution for the same RFE. We used the International Classicication of Primary
      Care, Revised Second edition (ICPC-2-R) codes for RFEs and diagnoses. RESULTS:
      The main RFE fields were digestive (ICPC-2-R Chapter D), general and unspecified
      (A), and respiratory (R). The main diagnosis fields were digestive (D),
      respiratory (R), general and unspecified (A), and musculoskeletal (L). In total,
      27.6% of patients had sought consultation at another medical institution for the
      same RFE. Of these, 64.7% of patients for whom the RFE was cough (ICPC-2-R code,
      R05), and 72.0% for whom the RFE was fever (A03) were prescribed antibiotics. In
      total, 62.4% of patients underwent emergency investigations and waited for the
      results; 4.3% were hospitalized on the same day; and 60.5% were medicated at the
      initial examination. In 11.5%, the main underlying problem appeared to be
      psychosomatic. CONCLUSION: We used the ICPC-2-R to analyze the state of first
      visit patients without a referral visiting the Department of Internal Medicine at
      a medium-sized acute care hospital in Japan. Common RFEs were abdominal pain,
      cough, and fever. A tendency toward overprescription of antibiotics was observed
      among primary care physicians.

PMID- 29042809
TI  - Implementation of GINA guidelines in asthma management by primary care physicians
      in Vietnam.
AB  - BACKGROUND: Asthma control is suboptimal in Vietnam. Lack of knowledge of primary
      care physicians (PCPs) for asthma management may potentially be one of the
      causes. PURPOSE: The aim of this study was to assess the knowledge and practice
      of PCPs' asthma management based on the Global Initiative for Asthma (GINA)
      guidelines (2015 update). METHODS: A cross-sectional study with convenience
      sampling was conducted among PCPs in an urban and rural area of Vietnam using
      questionnaires related to asthma patients daily practice: use of spirometry and
      the asthma control test (ACT), prescription of asthma medications, and frequency
      of consultations. Five asthma case scenarios were also used to ask participants
      to classify GINA-defined levels of asthma control and to choose the initial or
      adjusted treatment options based on the current situation. All scenarios are
      common in Vietnam, ie, three cases for adults, one case for children, and one
      case for pregnant women. RESULTS: Of the 327 completed questionnaires, 201
      questionnaires could be analyzed. Most PCPs consulted their asthma patients on a
      weekly to monthly basis. Approximately 50% used spirometry for asthma care and
      only 25% used ACT. For asthma treatment, oral short-acting beta agonists and oral
      steroids were still commonly used and long-acting beta agonists alone were
      prescribed by 70%. Regarding GINA-defined levels of asthma control, 24% of the
      responders had >=50% of correct answers, 21% had no correct answers, 2% had all
      five correct answers, and 20-42% had a correct answer for each of the five
      questions. Regarding treatment choice, 22% had >=50% of correct answers, 14% had
      a wrong answer for all nine questions, and no respondent had a correct answer for
      >=8 questions. CONCLUSION: The percentage of PCPs in Vietnam who had implemented
      GINA 2015 was low. Some drugs with a high risk of side effects were still being
      prescribed. There is a need to improve both knowledge and daily practice.
      Additional studies should determine why these guidelines are not largely adopted
      by PCPs in Vietnam.

PMID- 29042810
TI  - Changes in pain and concurrent pain medication use following compounded topical
      analgesic treatment for chronic pain: 3- and 6-month follow-up results from the
      prospective, observational Optimizing Patient Experience and Response to Topical
      Analgesics study.
AB  - BACKGROUND: Opioids and other controlled substances prescribed for chronic pain
      are associated with abuse, addiction, and death, prompting national initiatives
      to identify safe and effective pain management strategies including topical
      analgesics. METHODS: This prospective, observational study evaluated changes from
      baseline in overall mean severity and interference scores on the Brief Pain
      Inventory scale and the use of concurrent pain medications at 3- and 6-month
      follow-up assessments in chronic pain patients treated with topical analgesics.
      Changes in pain severity and interference and medication usage were compared
      between treated patients and unmatched and matched controls. RESULTS: The
      unmatched intervention group (unmatched-IG) included 631 patients who completed
      baseline and 3-month follow-up surveys (3-month unmatched-IG) and 158 who
      completed baseline and 6-month follow-up assessments (6-month unmatched-IG).
      Baseline and 3-month follow-up data were provided by 76 unmatched controls and 76
      matched controls (3-month unmatched-CG and matched-CG), and 51 unmatched and 36
      matched patients completed baseline and 6-month follow-up surveys (6-month
      unmatched-CG and matched-CG). Baseline demographic characteristics and mean pain
      severity and interference scores were similar between groups. There were
      statistically significant decreases from baseline in mean pain severity and
      interference scores within the 3- and 6-month unmatched-IG (all P<0.001).
      Significantly greater decreases in the mean change from baseline in pain severity
      and interference scores were evident for the 3- and 6-month unmatched-IG versus
      unmatched-CG (all P<0.001), with similar results when the 3- and 6-month matched
      IG and matched-CG were compared. A higher percentage of the 3- and 6-month
      unmatched-IG and matched-IG de-escalated use of concurrent pain medications (all
      P<0.001), while significantly higher percentages of the unmatched-CG and matched
      CG escalated medication use. Side effects were reported by <1% of the unmatched
      IG. CONCLUSION: Topical analgesics appear to be effective and safe for the
      treatment of chronic pain, with randomized controlled trials needed to confirm
      these findings.

PMID- 29042811
TI  - Optical inactivation of the anterior cingulate cortex modulate descending pain
      pathway in a rat model of trigeminal neuropathic pain created via chronic
      constriction injury of the infraorbital nerve.
AB  - PURPOSE: The anterior cingulate cortex (ACC) plays a critical role in the
      initiation, development, and maintenance of neuropathic pain. Recently, the
      effects of optical stimulation on pain have been investigated, but the
      therapeutic effects of optical stimulation on trigeminal neuralgia (TN) have not
      been clearly shown. Here, we investigated the effects of optical inhibition of
      the ACC on TN lesions to determine whether the alleviation of pain affects
      behavior performance and thalamic neuron signaling. MATERIALS AND METHODS: TN
      lesions were established in animals by generating a chronic constriction injury
      of the infraorbital nerve, and the animals received injections of AAV-hSyn
      eNpHR3.0-EYFP or a vehicle (phosphate-buffered saline [PBS]) in the ACC. The
      optical fiber was fixed into the ipsilateral ACC after the injection of adeno
      associated virus plasmids or vehicle. Behavioral testing, consisting of responses
      to an air puff and cold allodynia, was performed, and thalamic neuronal activity
      was monitored following optical stimulation in vivo. Optical stimulation
      experiments were executed in three steps: during pre-light-off, stimulation-light
      on, and post-light-off states. The role of the optical modulation of the ACC in
      response to pain was shown using a combination of optical stimulation and
      electrophysiological recordings in vivo. RESULTS: Mechanical thresholds and
      facial cold allodynia scores were significantly improved in the TN lesion group
      during optical stimulation compared to those in the control group. Thalamic
      neuronal activity, consisting of the firing rate (spikes/s) and burst rate
      (bursts/s), was also decreased during optical stimulation. CONCLUSION: Reciprocal
      optical inhibition of the ACC can alleviate pain-associated behavior and decrease
      abnormal thalamic sensory neuron activity in the trigeminal neuropathic rat
      model. The descending pain pathway can modulate thalamic neurons from the ACC
      following optical stimulation.

PMID- 29042812
TI  - Age differences in salivary markers of inflammation in response to experimental
      pain: does venipuncture matter?
AB  - An important consideration in mechanistic research using biomarkers should
      include the use of saliva as an alternative to blood. The use of saliva would
      allow the study of susceptible populations such as older adults where
      venipuncture may not be feasible. Although saliva has been most commonly used to
      measure cortisol and tumor necrosis factor-alpha (TNFalpha), there is limited
      evidence that other cytokines found in saliva significantly change in response to
      laboratory-induced pain. Therefore, the aim of the current preliminary study was
      to characterize the time course, duration and magnitude of changes of commonly
      measured pro- (interleukin [IL]-6, IL-8) and anti-inflammatory (IL-10, IL-4)
      cytokines in saliva samples and to test for age-related differences in separate
      experimental painful and non-painful control sessions. In addition, we also
      tested whether venipuncture results in significant cytokine alterations similar
      to a painful stimulus in a non-painful, non-venipuncture control session. All
      cytokines were significantly induced by the cold pressor task compared to a warm
      control session (p < 0.001). Specifically, healthy older adults experienced
      greater salivary changes in all cytokines during the cold pressor session
      compared to younger adults in the non-painful sessions (p < 0.001). There were no
      significant differences between the venipuncture and non-venipuncture sessions
      across all cytokines (p > 0.05). Our findings support the use of saliva as a
      substitute for blood in both young and older healthy individuals to measure
      changes after experimental pain stimulation. In addition, venipuncture alone is
      not sufficient to induce IL-6, IL-8, IL-10 and IL-4. Future studies in the
      community are urgently needed to validate and further move translational
      mechanistic pain research to those populations most underrepresented in clinical
      research.

PMID- 29042814
TI  - Attenuated serum adiponectin levels are associated with disease severity in
      patients with non-traumatic osteonecrosis of the femoral head.
AB  - OBJECTIVE: Decreased adiponectin (APN) levels have been detected in patients with
      osteonecrosis of the femoral head (ONFH). The scope of this study was aimed to
      explore the relationship between serum APN levels and disease severity in
      nontraumatic ONFH patients. PATIENTS AND METHODS: Ninety two nontraumatic ONFH
      patients and 92 healthy controls were enrolled for this study following the
      estimation of sample size. Serum APN concentrations were examined by enzyme
      linked immunosorbent assay (ELISA). The radiographic progression was determined
      by Ficat grading system. The clinical severity was evaluated by visual analog
      scale (VAS), Harris hip scores (HSSs) and Western Ontario and McMaster University
      Osteoarthritis Index (WOMAC) scores. RESULTS: Serum APN levels were significantly
      lower in ONFH patients than in healthy controls. Serum APN levels were
      significantly lower in patients with Ficat stage 4 ONFH than in patients with
      stage 3 ONFH, and APN levels in patients with stage 3 were lower compared with
      stage 2. Serum APN levels were negatively correlated with the Ficat grading
      system. In addition, serum APN levels were also negatively related to VAS and
      WOMAC scores and positively associated with HSSs. CONCLUSION: Decreased serum APN
      levels may reflect disease severity of nontraumatic ONFH.

PMID- 29042813
TI  - Rehabilitation management of low back pain - it's time to pull it all together!
AB  - In the past, rehabilitation research initiatives for low back pain (LBP) have
      targeted outcome enhancement through personalized treatment approaches, namely
      through classification systems (CS). Although the use of CS has enhanced
      outcomes, common management practices have not changed, the prevalence of LBP is
      still high, and only selected patients meet the CS profile, namely those with a
      nociceptive context. Similarly, although practice guidelines propose some level
      of organization and occasionally a timeline of care provision, each mainly
      provides best practice for isolated treatment approaches. Moreover, there is no
      theoretical framework that has been proposed that guides the rehabilitation
      management process of mechanical LBP. In this commentary, we propose a model
      constituted of five domains (nociceptive drivers, nervous system dysfunction
      drivers, comorbidities drivers, cognitive-emotional drivers, and contextual
      drivers) grounded as mechanisms driving pain and/or disability in LBP. Each
      domain is linked to the International Classification of Functioning, Disability
      and Health, where once a patient is deemed suitable for rehabilitation, the
      clinician assesses elements of each domain in order to identify where the
      relative treatment efforts should be focused. This theoretical model is designed
      to provide a more comprehensive management overview, by appreciating the relative
      contribution of each domain driving pain and disability. Considering that the
      multiple domains driving pain and disability, and their interaction, requires a
      model that is comprehensive enough to identify and address each related issue, we
      consider that the proposed model has several positive implications for
      rehabilitation of this painful and highly prevalent musculoskeletal disorder.

PMID- 29042815
TI  - The role of miR-190a-5p contributes to diabetic neuropathic pain via targeting
      SLC17A6.
AB  - INTRODUCTION: MicroRNAs play a key role in neuropathic pain. In a previous study,
      miR-190a-5p was significantly downregulated in diabetic neuropathic pain (DNP).
      However, the role and pathological mechanism of miR-190a-5p in DNP still remain
      unclear. MATERIALS AND METHODS: DNP model was established. The paw withdrawal
      thresholds were measured to assess the mechanical nociceptive response. Dual
      luciferase reporter assay was used to confirm the target gene of microRNA. The
      expressions of microRNA, gene, and protein were detected by the quantitative real
      time polymerase chain reaction or Western blot. The levels of IL-1beta and IL-6
      were detected with the enzyme-linked immuno sorbent assay. RESULTS: Compared with
      the control sample, the expression of miR-190a-5p was decreased and SLC17A6 was
      increased in the spinal tissue from those developing DNP. The bioinformatics and
      luciferase reporter assay demonstrated that SLC17A6 is a direct target of miR
      190a-5p. Up-regulation of miR-190a-5p and inhibition of SLC17A6 could
      significantly weaken the painful behavior and reduce IL-1beta and IL-6 level in
      DNP. CONCLUSION: miR-190a-5p is involved in DNP via targeting SLC17A6, and miR
      190a-5p and SLC17A6 may be the therapeutic targets of this disease.

PMID- 29042816
TI  - Incidence and predictive factors of spinal cord stimulation treatment after
      lumbar spine surgery.
AB  - INTRODUCTION: Spinal cord stimulation (SCS) is recommended for the treatment of
      postsurgical chronic back and leg pain refractory to other treatments. We wanted
      to estimate the incidence and predictive factors of SCS treatment in our lumbar
      surgery cohort. PATIENTS AND METHODS: Three questionnaires (a self-made
      questionnaire, the Oswestry Low Back Pain Disability Questionnaire, and the Beck
      Depression Inventory) were sent to patients aged 18-65 years with no
      contraindications for the use of SCS, and who had undergone non-traumatic lumbar
      spine surgery in the Oulu University Hospital between June 2005 and May 2008.
      Patients who had a daily pain intensity of >=5/10 with predominant radicular
      component were interviewed by telephone. RESULTS: After exclusions, 814 patients
      remained in this cohort. Of those, 21 patients had received SCS by the end of
      June 2015. Fifteen (71%) of these received benefit and continued with the
      treatment. Complications were rare. The number of patients who replied to the
      postal survey were 537 (66%). Eleven of them had undergone SCS treatment after
      their reply. Features predicting SCS implantation were daily or continuous pain,
      higher intensities of pain with predominant radicular pain, more severe pain
      related functional disability, a higher prevalence of depressive symptoms, and
      reduced benefit from pain medication. The mean waiting time was 65 months (26-93
      months). One hundred patients were interviewed by telephone. Fourteen seemed to
      be potential SCS candidates. From the eleven patients who underwent SCS after
      responding to the survey, two were classified as potential candidates in the
      phone interview, while nine were other patients. Twelve patients are still
      waiting for treatment to commence. CONCLUSION: In our region, the SCS treatment
      is used only for very serious pain conditions. Waiting time is too long and it
      may be the reason why this treatment option is not offered to all candidates.

PMID- 29042817
TI  - Accuracy of the hypospadias diagnoses and surgical treatment registrations in the
      Danish National Patient Register.
AB  - PURPOSE: The Danish National Health registers provide a valuable data source that
      offers unique opportunities for observational research, including studies on the
      congenital anomaly hypospadias. The accuracy of the diagnosis and surgical
      treatment registration of hypospadias in the Danish National Patient Register
      (DNPR) remains unknown. PATIENTS AND METHODS: We randomly sampled 500 patients
      diagnosed with hypospadias in the DNPR from January 1, 1995 to December 31, 2012.
      Among these, 384 patients were also registered with surgical treatment for
      hypospadias. Medical records were collected and reviewed independently by two
      investigators. Any classification disagreements were resolved by consensus. Using
      the medical records as the gold standard, we estimated positive predictive values
      (PPVs) with 95% confidence intervals (CIs) for the hypospadias diagnoses and
      surgical treatment registrations overall, as well as for the clinical subtypes.
      RESULTS: We were able to retrieve medical records for 463 (92.6%) patients with
      hypospadias diagnoses and for 329 (85.7%) patients registered with surgical
      treatment. Presence of hypospadias was confirmed in 450 of 463 patients, yielding
      an overall PPV (95% CI) of 97.6% (95.8%-98.7%). For subtypes of hypospadias, the
      PPVs ranged between 37.5% and 72.7%. For surgical treatment of hypospadias, the
      overall PPV was 99.7% (97.9%-99.9%). CONCLUSION: The validity of the registration
      of hypospadias diagnoses as well as surgical treatment for hypospadias in the
      DNPR is overall very high. For the specific subtypes of hypospadias diagnoses
      codes and the specific surgical treatment codes, the PPVs are lower and cautious
      use is warranted. However, the DNPR remains a valuable tool for future
      observational research on hypospadias.

PMID- 29042818
TI  - Cycle control with an extended-regimen oral contraceptive combining
      levonorgestrel and ethinyl estradiol that includes continuous low-dose ethinyl
      estradiol instead of the traditional hormone-free interval.
AB  - PURPOSE: To evaluate scheduled and unscheduled bleeding and spotting over 1 year
      of treatment with 91-day extended-regimen combined oral contraception (COC)
      providing continuous low-dose ethinyl estradiol (EE) in place of the traditional
      7-day hormone-free interval (HFI). PATIENTS AND METHODS: This post hoc analysis
      of a multicenter, open-label, 1-year, Phase 3 study of extended-regimen COC with
      30 ug EE/150 ug levonorgestrel (LNG) for 84 days and EE 10 ug for 7 days included
      799 sexually active, adult women who completed at least one 91-day cycle of
      therapy. Subjects recorded bleeding and spotting episodes daily using electronic
      diaries. Logistic regression analyses are reported as ORs with 95% CIs. RESULTS:
      There was a 10% increase (OR =1.102; 95% CI: 1.006-1.206) in the likelihood of
      reporting no scheduled bleeding for each additional 91-day cycle completed. From
      the third 91-day cycle, more than one fifth of women reported no scheduled
      bleeding (third cycle =23% [121/533]; fourth cycle =22% [97/446]). Among women
      who reported no scheduled bleeding at Cycle 1 (136/758 [18%]), >=45% showed
      sustained lack of scheduled bleeding in later cycles. There were increases of 53%
      (OR =1.531; 95% CI: 1.393-1.683) and 31% (OR =1.307; 95% CI: 1.205-1.418) in the
      likelihood of reporting 0 to <=6 days vs >6 days of unscheduled bleeding and
      spotting, respectively, for each additional 91-day cycle. By Cycle 2, more than
      80% of women reported no unscheduled bleeding or <=6 days of unscheduled bleeding
      during each 91-day cycle. CONCLUSION: Improved cycle control with decreased
      bleeding over time was shown during extended-regimen COC with 30 ug EE/150 ug LNG
      for 84 days and continuous low-dose EE instead of the traditional 7-day HFI.
      Women considering this regimen should be informed that those who complete at
      least one 91-day COC cycle will likely experience less bleeding/spotting in
      future cycles.

PMID- 29042819
TI  - Distance from health facility and mothers' perception of quality related to
      skilled delivery service utilization in northern Ethiopia.
AB  - BACKGROUND: Poor maternal health service utilization is one of the contributing
      factors to a high level of maternal and newborn mortality in Ethiopia. The
      factors associated with utilization of services are believed to differ from one
      context to another. We assessed the factors associated with skilled delivery
      service utilization in rural northern Ethiopia. SUBJECTS AND METHODS: A community
      based survey was conducted among mothers who gave birth in the 12 months
      preceding the study period, from January to February 2015, in the Tigray region
      of Ethiopia. Multistage sampling technique was used to select mothers from the
      identified clusters. Households within a 10 km radius of the health facility were
      taken as a cluster for a community survey. Data were collected using face-to-face
      interview at the household level. We compared the mothers who reported giving
      birth to the index child in a health facility and those who reported delivering
      at home, in order to identify the predictors of skilled delivery utilization.
      Multivariable logistic regression model was used to determine the predictors of
      skilled delivery service utilization. The results are presented with odds ratio
      (OR) and 95% confidence interval (CI). RESULTS: A total of 1,796 mothers
      participated in the study, with a 100% response rate. Distance to health
      facilities (adjusted odds ratio [AOR] =0.53 [95% CI: 0.39, 0.71]), perception of
      mothers to the availability of adequate equipment in the delivery service in
      their catchment area (AOR =1.5 [95% CI: 1.11, 2.13]), experiencing any
      complication during childbirth, using antenatal care, lower birth order and
      having an educated partner were the significant predictors of skilled delivery
      service utilization. CONCLUSION: Implementing community-based intervention
      programs that will address the physical accessibility of delivery services, such
      as the ambulance service, road issues and waiting rooms, and improving quality
      maternity service will likely reduce the current problem.

PMID- 29042820
TI  - Necrobiotic xanthogranuloma scleritis in a case of granulomatosis with
      polyangiitis (Wegener's granulomatosis).
AB  - The purpose of this study was to describe a case of necrobiotic xanthogranuloma
      scleritis in a 53-year-old male with unilateral progressive visual loss,
      scleritis, prolonged fever, and multiple mononeuropathy. Scleral biopsy showed
      necrosis with small abscess, and the pathological tissues revealed submucosal
      infiltration of mononucleated foamy histiocytes (xanthoma cells), hemosiderin
      laden macrophages, neutrophils, lymphocytes, plasma cells, and erythrocytes
      without Touton giant cells or cholesterol clefts. Serum protein electrophoresis
      showed polyclonal gammopathy. All infectious investigations were negative.
      Afterward, this patient was diagnosed with granulomatosis with polyangiitis based
      on granuloma found in scleral tissue, vasculitis seen in sural nerve biopsy and
      positive serologies (C-ANCA and anti-PR3 antibody). He was treated with high-dose
      corticosteroid and later with intravenous cyclophosphamide monthly. He responded
      well to treatment, both eye and systemic conditions. Necrobiotic xanthogranuloma
      scleritis could be an early presentation of granulomatosis with polyangiitis.

PMID- 29042822
TI  - Antipsychotic prescription to identify delirium: results from two cohorts.
AB  - OBJECTIVES: Detection of delirium in hospitalized patients remains challenging.
      The objective was to determine if the prescription of antipsychotic medications
      was associated with delirium. PATIENTS AND METHODS: Two patient cohorts were
      utilized from a tertiary Veterans Affairs hospital: a palliative care
      retrospective cohort and a prospective medical cohort. Patients prescribed
      outpatient antipsychotics were excluded. Retrospectively, delirium was identified
      using a validated medical record-review instrument. Prospectively, a clinical
      expert assessed patients for delirium daily using a standardized interview. Acute
      antipsychotic medication administration was recorded from the electronic medical
      record. RESULTS: In the retrospective cohort (n=217), delirium was found in 31%
      (n=67) and antipsychotic use in 18% (n=40) of patients. Acute antipsychotic use
      indicated delirium with 54% sensitivity and 97% specificity. In the prospective
      cohort (n=100), delirium developed in 23% (n=23) and antipsychotics were used in
      5% (n=5) of patients. The sensitivity and specificity of acute antipsychotic use
      was 22% and 100%, respectively. CONCLUSION: Hospitalized patients who are acutely
      prescribed antipsychotics are likely to have delirium, but not all patients with
      delirium will be identified with this method. In health systems, utilization of
      the prescription of acute antipsychotics can be an efficient and specific method
      to identify delirious patients for targeted intervention.

PMID- 29042821
TI  - Practical recommendations for the use of therapeutic drug monitoring of
      biopharmaceuticals in inflammatory diseases.
AB  - Biopharmaceuticals directed against tumor necrosis factor-alpha, integrins,
      interleukins, interferons and their receptors have become key agents for the
      management of inflammatory diseases in the fields of gastroenterology,
      rheumatology, dermatology and neurology. However, response to these treatments is
      far from optimal. Therapeutic failure has been attributed in part to inadequate
      serum concentrations of the drug and the formation of antidrug antibodies (ADA).
      Therapeutic drug monitoring (TDM) based on drug concentrations and ADA represents
      a pharmacologically sound tool for guiding dosage adjustments to optimize
      exposure. Although becoming standard practice in tertiary care centers, the
      widespread accessibility and recognition of TDM is hindered by several hurdles,
      including a lack of education of health care providers on TDM. In this paper, the
      Monitoring of monoclonal Antibodies Group in Europe (MAGE) provides an
      introduction on the fundamental principles of the concept of TDM, aiming to
      educate clinicians and assist them in the process of implementing TDM of anti
      inflammatory biopharmaceuticals.

PMID- 29042823
TI  - Digital health technology for use in patients with serious mental illness: a
      systematic review of the literature.
AB  - BACKGROUND: As the capabilities and reach of technology have expanded, there is
      an accompanying proliferation of digital technologies developed for use in the
      care of patients with mental illness. The objective of this review was to
      systematically search published literature to identify currently available health
      technologies and their intended uses for patients with serious mental illness.
      MATERIALS AND METHODS: The Medline, Embase, and BIOSIS Previews electronic
      databases were searched to identify peer-reviewed English language articles that
      reported the use of digital, mobile, and other advanced technology in patients
      with schizophrenia/schizoaffective disorder, bipolar disorder, and major
      depressive disorder. Eligible studies were systematically reviewed based on
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      guidelines. RESULTS: Eighteen studies that met the inclusion criteria were
      identified. Digital health technologies (DHTs) assessed in the selected studies
      included mobile applications (apps), digital medicine, digital personal health
      records, and an electronic pill container. Smartphone apps accounted for the
      largest share of DHTs. The intended uses of DHTs could be broadly classified as
      monitoring to gain a better understanding of illness, clinical assessment, and
      intervention. Overall, studies indicated high usability/feasibility and
      efficacy/effectiveness, with several reporting validity against established
      clinical scales. Users were generally engaged with the DHT, and mobile
      assessments were deemed helpful in monitoring disease symptoms. CONCLUSION:
      Rapidly proliferating digital technologies seem to be feasible for short-term use
      in patients with serious mental illness; nevertheless, long-term effectiveness
      data from naturalistic studies will help demonstrate their usefulness and
      facilitate their adoption and integration into the mental health-care system.

PMID- 29042824
TI  - Family profiles in eating disorders: family functioning and psychopathology.
AB  - Research has studied family functioning in families of patients suffering from
      eating disorders (EDs), particularly investigating the associations between
      mothers' and daughters' psychopathological symptoms, but limited studies have
      examined whether there are specific maladaptive psychological profiles
      characterizing the family as a whole when it includes adolescents with anorexia
      nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Through the
      collaboration of a network of public and private consultants, we recruited n=181
      adolescents diagnosed for EDs (n=61 with AN, n=60 with BN, and n=60 with BEDs)
      and their parents. Mothers, fathers, and youths were assessed through a self
      report measure evaluating family functioning, and adolescents completed a self
      report questionnaire assessing psycho-pathological symptoms. Results showed
      specific family functioning and psychopathological profiles based on adolescents'
      diagnosis. Regression analyses also showed that family functioning characterized
      by rigidity predicted higher psychopathological symptoms. Our study underlines
      the importance of involving all members of the family in assessment and
      intervention programs when adolescent offspring suffer from EDs.

PMID- 29042826
TI  - Clinical reasoning and knowledge management in final year medical students: the
      role of Student-led Grand Rounds.
AB  - OBJECTIVES: The development of clinical reasoning and decision-making skills is
      often limited in medical school curricula. In reality, medical graduates acquire
      these skills during their first few years of residency. For many, this can be
      stressful as they may be working under limited supervision as a part of their
      rotations. METHODS: Student-led Grand Rounds was developed to transfer both
      explicit and tacit knowledge to final year medical students. This pilot project
      was to apply the principles of knowledge management to allow students to be
      exposed to the reasoning and decision making of common clinical presentations.
      Student feedback through questionnaires was collated at the end of the program.
      RESULTS: Based on feedback and focus groups, modifications were made to produce a
      stable program in subsequent clinical rotations. Formal feedback was collated
      from all the 76 students who participated in the first year. This represented
      100% of the cohort for this clinical school for that year. There was a 100%
      response rate as the feedback forms were given and collected at the end of the
      last session per block. The student responses were both in ratings defined in a
      feedback forms and in written comments. A total of 74 of the 76 students rated
      the program highly. They enjoyed the nonthreatening interactions. The remaining
      two students preferred more didactic teaching. CONCLUSION: This initiative allows
      an efficient transfer and utilization of knowledge. This could maximize the
      acquisition of practical knowledge by medical students as they finish their
      course in the transition to graduate medical practice.

PMID- 29042825
TI  - Antithrombotics in trauma: management strategies in the older patients.
AB  - The ageing population has resulted in a change in the demographics of trauma, and
      older adult trauma now accounts for a growing number of trauma admissions. The
      management of older adult trauma can be particularly challenging, and exhibits
      differences to that of the younger age groups affected by trauma. Frailty
      syndromes are closely related with falls, which are the leading cause of major
      trauma in older adults. Comorbid disease and antithrombotic use are more common
      in the older population. Physiological changes that occur with ageing can alter
      the expected clinical presentation of older persons after injury and their
      susceptibility to injury. Following major trauma, definitive control of
      hemorrhage remains essential for improving outcomes. In the initial assessment of
      an injured patient, it is important to consider whether the patient is taking
      anticoagulants or antiplatelets and if measures to promote hemostasis such as
      reversal are indicated. After hemostasis is achieved and bleeding has stopped,
      longer-term decisions to recommence antithrombotic agents can be challenging,
      especially in older people. In this review, we discuss one aspect of management
      for the older trauma patients in greater detail, that is, acute and longer-term
      management of antithrombotic therapy. As we consider the health needs of an
      ageing population, rise in elderly trauma and increasing use of antithrombotic
      therapy, the need for research in this area becomes more pressing to establish
      best practice and evidence-based care.

PMID- 29042827
TI  - Use of a problem-based learning teaching model for undergraduate medical and
      nursing education: a systematic review and meta-analysis.
AB  - OBJECTIVES: The aim of this systematic review and meta-analysis was to evaluate
      the problem-based learning (PBL) method as an alternative to conventional
      educational methods in Iranian undergraduate medical courses. MATERIALS AND
      METHODS: We systematically searched international datasets banks, including
      PubMed, Scopus, and Embase, and internal resources of banks, including MagirIran,
      IranMedex, IranDoc, and Scientific Information Database (SID), using appropriate
      search terms, such as "PBL", "problem-based learning", "based on problems",
      "active learning", and" learner centered", to identify PBL studies, and these
      were combined with other key terms such as "medical", "undergraduate", "Iranian",
      "Islamic Republic of Iran", "I.R. of Iran", and "Iran". The search included the
      period from 1980 to 2016 with no language limits. RESULTS: Overall, a total of
      1,057 relevant studies were initially found, of which 21 studies were included in
      the systematic review and meta-analysis. Of the 21 studies, 12 (57.14%) had a
      high methodological quality. Considering the pooled effect size data, there was a
      significant difference in the scores (standardized mean difference [SMD]=0.80,
      95% CI [0.52, 1.08], P<0.000) in favor of PBL, compared with the lecture-based
      method. Subgroup analysis revealed that using PBL alone is more favorable
      compared to using a mixed model with other learning methods such as lecture-based
      learning (LBL). CONCLUSION: The results of this systematic review showed that
      using PBL may have a positive effect on the academic achievement of undergraduate
      medical courses. The results suggest that teachers and medical education decision
      makers give more attention on using this method for effective and proper
      training.

PMID- 29042828
TI  - Predictors of sedentary status in overweight and obese patients with multiple
      chronic conditions: a cohort study.
AB  - PURPOSE: Walking may improve health in obese patients with multimorbidity. We
      aimed to identify predictors associated with achieving <5000 steps per day after
      4 months. PATIENTS AND METHODS: We conducted a cohort study of 125 adult patients
      with a body mass index >25 kg/m2 and >=7 comorbidities. We evaluated potential
      predictors for <5000 steps per day using logistic regression and adjusting for
      age >65 years and sex. RESULTS: The mean (range) age was 63.6 (20.3-89.8) years.
      Daily step counts <5000 at baseline showed the highest risk of <5000 daily steps
      at 4 months (odds ratio [OR] 31.82, 95% confidence interval [CI]: 12.14-95.50).
      Other significant characteristics were physical quality of life (OR 6.21, 95% CI:
      2.32-18.54), gait speed <1 m/s (OR 2.57, 95% CI: 1.18-5.71), age >=65 years (OR
      2.21, 95% CI: 1.05-4.77), waist circumference >=102 cm (OR 2.48, 95% CI: 1.05
      6.06), and body mass index >=30 kg/m2 (OR 2.69, 95% CI: 1.20-6.26). CONCLUSION:
      New models to increase walking may be required for higher-risk patients.

PMID- 29042829
TI  - Kinetics of N-Glycan Release from Human Immunoglobulin G (IgG) by PNGase F: All
      Glycans Are Not Created Equal.
AB  - The biologic activity of IgG molecules is modulated by its crystallizable
      fragment N-glycosylation, and thus, the analysis of IgG glycosylation is
      critical. A standard approach to analyze glycosylation of IgGs involves the
      release of the N-glycans by the enzyme peptide N-glycosidase F, which cleaves the
      linkage between the asparagine residue and innermost N-acetylglucosamine (GlcNAc)
      of all N-glycans except those containing a 3-linked fucose attached to the
      reducing terminal GlcNAc residue. The importance of obtaining complete glycan
      release for accurate quantitation led us to investigate the kinetics of this de
      glycosylation reaction for IgG glycopeptides and to determine the effect of
      glycan structure and amino acid sequence on the rate of glycan release from
      glycopeptides of IgGs. This study revealed that the slight differences in amino
      acid sequences did not lead to a statistically different deglycosylation rate.
      However, statistically significant differences in the deglycosylation rate
      constants were observed between glycopeptides differing only in glycan structure
      (i.e., nonfucosylated, fucosylated, bisecting-GlcNAc, sialylated, etc.). For
      example, a single sialic acid residue was found to decrease the rate by a factor
      of 3. Similar reductions in rate were associated with the presence of a bisecting
      GlcNAc. We predict the differences in release kinetics can lead to significant
      quantitative variations of the glycosylation study of IgGs.

PMID- 29042830
TI  - Evaluation of the effects of two doses of alpha glycerylphosphorylcholine on
      physical and psychomotor performance.
AB  - BACKGROUND: Recent studies have suggested that alpha glycerylphosphorylcholine (A
      GPC) may be an effective ergogenic aid. The present study was designed to assess
      the efficacy of two doses of A-GPC in comparison to placebo and caffeine for
      increasing countermovement jump performance, isometric strength, and psychomotor
      function. METHODS: Forty-eight healthy, college aged males volunteered for the
      present study and underwent baseline assessment of countermovement jump (CMJ),
      isometric mid thigh pull (IMTP), upper body isometric strength test (UBIST), and
      psychomotor vigilance (PVT). Following this assessment participants were randomly
      assigned to groups consisting of 500 mg A-GPC, 250 mg A-GPC, 200 mg Caffeine or
      Placebo taken daily. Blood samples were collected 1 h and 2 h post initial dose
      to quantify serum free choline and thyroid stimulating hormone then subjects
      returned after 7 days of supplementation to repeat CMJ, IMTP, UBIST and PVT.
      RESULTS: No differences were noted between groups for IMTP, UBIST or PVT
      performance. Serum free choline was found to be elevated in the two A-GPC groups
      as compared to placebo (132% and 59% respectively). Serum TSH was found to be
      significantly depressed in the 500 mg A-GPC group compared to other treatments (p
      < 0.04). Group differences were noted for maximum velocity and maximum mechanical
      power on the CMJ (p < 0.05) with the 250 mg A-GPC group demonstrating the
      greatest improvements in result. CONCLUSIONS: Based upon this evidence, and
      previous evidence regarding A-GPC, it should be considered as an emerging
      ergogenic supplement.

PMID- 29042831
TI  - The Impact of Antithrombin III Use in Achieving Anticoagulant Goals in Pediatric
      Patients.
AB  - OBJECTIVES: To determine the percentage of patients with >10% reduction in
      heparin infusion rate within 48 hours of antithrombin III (ATIII) administration.
      Secondary objectives include the achievement of therapeutic anticoagulation and
      determining the days of subtherapeutic infusion prior to supplementation.
      METHODS: Retrospective chart review of 12 patients younger than 18 years of age
      who received ATIII concentrate supplementation while on continuous heparin
      infusion. Specific indications for heparin infusion therapy included
      extracorporeal membrane oxygenation (ECMO), treatment of thrombus, and post
      implantation of ventricular assist device(s). RESULTS: From time of heparin
      initiation to ATIII supplementation, patients spent a mean 4.9 +/- 2.6 days of
      subtherapeutic infusion and required uptitration from a mean of 15.3 +/- 4.4
      units/kg/hr to a mean rate of 40.7 +/- 9.5 units/kg/hr. 58.3% of the patients (n
      = 7) had a >=10% reduction from the baseline heparin infusion rate within 48
      hours of ATIII administration. Those patients considered responders (>=10%
      reduction from baseline rate) had a slightly higher mean baseline antithrombin
      level (76.3% +/- 22.0% vs. 58.6% +/- 2.7% in non-responders, p = 0.1) and were
      administered comparable doses of ATIII. ATIII supplementation did appear to
      increase the time of therapeutic anticoagulation within the 48 hours.
      CONCLUSIONS: Administration of ATIII is associated with >10% decrease in heparin
      requirements in more than half of the patients identified. In those patients
      deemed non-responders, there was a trend towards lower baseline antithrombin
      serum levels. Further studies are warranted to determine if the lack of response
      in some patients is due to inadequate dosing of ATIII or any patient-related
      factors.

PMID- 29042832
TI  - Evaluation of the Efficacy of a Onetime Injectable Dexamethasone Administered
      Orally in the Pediatric Emergency Department for Asthma Exacerbation.
AB  - OBJECTIVE: This study assessed the efficacy of injectable dexamethasone
      administered orally in pediatric patients who presented to the emergency
      department with asthma exacerbation. METHODS: This was a retrospective study of
      patients 0 to 18 years of age who presented to and who were directly discharged
      from the emergency department at Moses H. Cone Memorial Hospital between
      September 1, 2012, and September 30, 2015, for the diagnosis of asthma or asthma
      exacerbation. Patients had to receive a onetime dose of injectable dexamethasone
      orally prior to discharge. Patients were followed for a 30-day period to identify
      the number of asthma relapses. RESULTS: Ninety-nine patients were included in
      this study. The average weight-based dose +/- SD of dexamethasone was 0.35 +/-
      0.18 mg/kg (range, 0.08-0.62 mg/kg) and the actual dose +/- SD was 10.58 +/- 1.92
      mg (range, 5-16 mg). Over a 30-day period, 6 patients (6%) had one repeated
      emergency department visit, 6 patients (6%) were admitted to the hospital, and 3
      patients (3%) presented to an outpatient clinic for asthma-related symptoms.
      CONCLUSIONS: Injectable dexamethasone administered orally may be an efficacious
      treatment for asthma exacerbation in pediatric patients. A randomized control
      trial comparing injectable dexamethasone administered orally to other
      dexamethasone formulations/routes of administration should be performed to
      adequately assess the bioequivalence and effectiveness of the former formulation.

PMID- 29042833
TI  - Impact of a Pharmacist-Led Chemotherapy Education Program on the Knowledge of
      Pediatric Hematology/Oncology Nurses.
AB  - OBJECTIVES: Medication errors involving chemotherapy are a serious source of
      avoidable medical harm that can result in chemotherapy-related adverse drug
      events. Efforts to reduce errors in the past decade have largely focused on
      chemotherapy errors at the prescriber level, using computerized or automated
      technology, but little has been done to ensure chemotherapy is administered
      accurately at the nursing level. The current study implemented a pharmacist-led,
      supplemental, institution-specific training program to nursing staff regarding
      the use of chemotherapy and to address knowledge deficits in newly hired nursing
      personnel. METHODS: Inpatient pediatric oncology nurses were eligible to
      participate in a 3-session educational program regarding chemotherapy principles,
      adverse event management, and supportive care. Pre- and posttests were
      administered during the sessions to assess baseline and acquired knowledge. An
      attitudes survey was given to nurses prior to their first session and after the
      last session to assess the nurse's comfort with administration and management of
      chemotherapy. RESULTS: Posttest scores following program implementation show a
      significant increase in baseline knowledge. Scores increased by 14.1% (p < 0.001)
      overall; they increased 6% (p = 0.266), 22% (p = <0.001), and 16.5% (p = <0.001)
      after sessions 1, 2, and 3, respectively. All respondents requested additional
      classes for orientation or continuing education. CONCLUSIONS: A pharmacist-led,
      educational program significantly improves knowledge of chemotherapy
      administration and monitoring in pediatric oncology nurses and was well received
      by participants as an additional training opportunity.

PMID- 29042834
TI  - Improving Palivizumab Compliance rough a Pharmacist-Managed RSV Prevention
      Clinic.
AB  - OBJECTIVES: Palivizumab is a monoclonal antibody approved for the prevention of
      serious lower respiratory tract infections caused by respiratory syncytial virus
      (RSV) in high-risk pediatric patients. While palivizumab is more effective if
      used correctly, compliance with the monthly dosing is suboptimal. We established
      a pharmacist-managed RSV prevention clinic in an effort to improve compliance.
      The primary objective of this study was to determine the impact of a pharmacist
      managed RSV prevention clinic on palivizumab compliance. METHODS: A chart review
      was performed. Patients who received palivizumab between September 2009 and April
      2012 were identified. Compliance was determined as the number of patients who
      received eligible doses at 28- to 30-day intervals, consecutively. RESULTS: One
      hundred seventy-two patients received at least 1 dose of palivizumab. An average
      of 92% of patients who received at least 1 dose subsequently received all doses
      of palivizumab during the RSV season. Of those, 88% received all eligible doses
      in consecutive 28-to 30-day intervals. CONCLUSION: A pharmacist-managed RSV
      prevention clinic can assist physicians in the prevention of RSV by increasing
      compliance with palivizumab dosing.

PMID- 29042835
TI  - Double-Blind Randomized Placebo-Controlled Trial of Single-Dose Intravenous
      Acetaminophen for Pain Associated With Adenotonsillectomy in Pediatric Patients
      With Sleep-Disordered Breathing.
AB  - OBJECTIVES: Adequate pain control is an important component in the postoperative
      outcome for pediatric adenotonsillectomy patients with sleep-disordered breathing
      (SDB). Intravenous acetaminophen appears to be a favorable analgesic adjunct
      owing to its predictable pharmacokinetics and opioid-sparing effects; however,
      its role in pediatric adenotonsillectomy pain management remains unclear.
      METHODS: In this prospective, randomized, double-blinded, controlled study,
      subjects with the diagnosis of SDB, aged 2 to 8 years, who required extended
      postoperative admission, received intravenous acetaminophen (15 mg/kg) or saline
      placebo intraoperatively in addition to morphine (0.1 mg/kg) for postoperative
      surgical analgesia. Pain scores in the postanesthesia care unit (PACU) using the
      FLACC (Faces, Leg, Activity, Cry, Consolability) score were used to determine the
      need for supplemental analgesic agents in the PACU. The PACU time and time to the
      first request for pain medication on the inpatient ward were also measured.
      RESULTS: A total of 239 patients were included in the final data analysis (118 in
      the intravenous acetaminophen group and 121 in the saline placebo group). The 2
      groups did not differ in the proportion of patients reaching FLACC scores = 4 in
      the PACU (p = 0.223); mean FLACC scores in the PACU (p = 0.336); mean PACU time
      (p = 0.883); or time to requesting pain medication on the inpatient ward (p =
      0.640). CONCLUSIONS: A single intraoperative dose of intravenous acetaminophen
      did not alter the postoperative course of pediatric patients with SDB following
      adenotonsillectomy.

PMID- 29042836
TI  - Evaluation of the Effects of Extracorporeal Membrane Oxygenation on Antiepileptic
      Drug Serum Concentrations in Pediatric Patients.
AB  - OBJECTIVES: Patients supported on extracorporeal membrane oxygenation (ECMO) have
      an increased incidence of seizures. Phenobarbital (PB) and fosphenytoin (fos-PHT)
      are common antiepileptic drugs (AEDs) used to manage seizures in the pediatric
      population; however, it is unknown what effect ECMO has on the serum
      concentrations of AEDs. The purpose of this study is to evaluate the effect of
      ECMO on AED serum concentrations. METHODS: A retrospective, matched-cohort study
      was performed in patients younger than 18 years who received ECMO and were
      treated with intravenous (IV) PB or fos-PHT at Texas Children's Hospital between
      2004 and 2014. Patients receiving IV AED therapy and ECMO were matched, based on
      age, sex, and weight, with patients receiving IV AED therapy without ECMO. The 24
      hour cumulative AED dose, serum concentrations, number of doses per serum
      concentration drawn ratio, volume of distribution, therapeutic serum
      concentrations, and time to therapeutic serum concentration were compared between
      both groups. The fos-PHT and PB groups were analyzed in all patients and in
      neonates only. RESULTS: Fourteen patients met inclusion criteria. The fos-PHT
      neonatal (20.1 vs 11.3 mg/kg/day, p = 0.044), PB composite (33.9 vs 21.6
      mg/kg/day, p = 0.012), and PB neonatal (40.3 vs 20 mg/kg/day, p = 0.04) had
      larger 24-hour cumulative doses compared with non-ECMO patients. Lower serum
      concentrations were observed in the PB composite ECMO group (19.1 vs 35.4 mg/L, p
      < 0.001) and the PB neonatal ECMO group (20.5 vs 27.8 mg/L, p = 0.01) compared
      with non-ECMO patients. CONCLUSION: Pediatric patients receiving PB on ECMO and
      neonatal patients receiving fos-PHT on ECMO required larger doses, and in
      pediatric patients achieved lower serum concentrations, suggesting the necessity
      for alternative dosing strategies in these populations.

PMID- 29042837
TI  - Vancomycin Dosing in Pediatric Extracorporeal Membrane Oxygenation: Potential
      Impacts of New Technologies.
AB  - OBJECTIVES: The objective of the current study was to evaluate the doses of
      vancomycin used to obtain therapeutic drug concentrations in pediatric patients
      on extracorporeal membrane oxygenation (ECMO), using new ECMO technologies.
      METHODS: This was a single-center, retrospective study of patients treated with
      vancomycin while receiving ECMO using low-volume circuit technology. RESULTS: A
      total of 28 patients were included in the analysis of the primary endpoint.
      Patients had a median age of 6 weeks (0-11 years) and a median weight of 3.45 kg
      (2.44-37.2 kg). Ultrafiltration was used in 89.3% of patients at initiation of
      ECMO regardless of baseline renal function, resulting in a median urine output of
      2 mL/kg/hr at the time of the final vancomycin dose. Most patients started
      vancomycin at the same time as ECMO. The median total daily dose was 30
      mg/kg/day. The median total daily dose in a subset of patients less than one year
      of age was 20 mg/kg/day. Nearly all patients had at least 1 therapeutic trough
      serum vancomycin concentration. A total of 16 patients completed their vancomycin
      course using an interval of every 12 hours or shorter. Half-life was calculated
      in a subset of 11 patients and the mean was found to be 12.3 +/- 2.8 hours.
      CONCLUSIONS: An initial dosing interval of every 12 hours to provide a total
      daily dose of 30 mg/kg/day is a possible option in pediatric patients on ECMO
      provided that renal function is normal at baseline. Monitoring of serum
      vancomycin concentrations for adjustment of dosing is required throughout therapy
      and is still warranted.

PMID- 29042838
TI  - Dose-Banding of Intravenous Piperacillin-Tazobactam in Pediatric Surgical
      Inpatients.
AB  - BACKGROUND: Antimicrobial doses in children are often prescribed by using an
      individually calculated dose per weight (e.g., mg/kg) or based on body surface
      area. Dosing errors are the most commonly reported medication errors in children.
      A "dose-banding" strategy is frequently used for some over-the-counter drugs to
      prevent dosing errors. It could also lead to efficiencies by enabling batch
      preparation of intravenous (IV) medications in hospitals. OBJECTIVES: To evaluate
      whether use of dose-banding for IV piperacillin-tazobactam results in acceptable
      dose variation from standard practice of individualized prescription of 100 mg/kg
      in children. METHODS: We conducted a historically controlled intervention study
      comparing prescriptions of IV piperacillin-tazobactam before vs. after
      introduction of dose-banding prescribing guidance for surgical inpatients
      weighing >5 kg and <16 years of age at the tertiary referral pediatric hospital
      in Western Australia. RESULTS: Dose-banding of IV piperacillin-tazobactam (with a
      maximum of 15% departure from the recommended milligram-per-weight dose of 100
      mg/kg) resulted in similar overall variation of prescribed dose in comparison to
      individualized milligram-per-weight (non-dose-banded) prescribing. There was a
      trend toward fewer prescriptions with large variance (>30% variation from the 100
      mg/kg dose) in the dose-banded compared to the non-dose-banded group (1/140 vs.
      5/105; p = 0.09). CONCLUSIONS: Our study showed dose-banding of IV piperacillin
      tazobactam resulted in acceptable variation when compared to individualized
      milligram-per-weight dosing in children. Prospectively designed controlled trials
      are warranted to determine whether dose-banding could reduce medication errors
      and optimize use of hospital resources. Implications for future practice could
      include faster batch preparation, shorter checking and dispensing time, and
      reduction in drug wastage.

PMID- 29042839
TI  - A Retrospective Study on Infusion-Related Reactions to Rituximab in a
      Heterogeneous Pediatric Population.
AB  - OBJECTIVES: To assess risks and outcomes of infusion-related reactions to
      rituximab in a heterogeneous pediatric population. METHODS: All patients who
      received rituximab between July 2010 and July 2012 were retrieved from the
      pharmacy software and included for analysis. Data were collected according to 4
      categories: demographic data, infusion data, infusion-related reactions, and
      biological data considered as risk factors (i.e., absolute lymphocyte count,
      lactate dehydrogenase levels). RESULTS: Sixty-seven patients treated for a total
      of 17 different indications were included. A total of 282 rituximab infusions
      were administered. Forty-three, mostly grade 1 or 2, infusion-related reactions
      occurred in 30 patients. Reactions occurred in 39.2% "first-dose" infusions, but
      this rate dropped drastically to 2.7% in subsequent doses. In multivariate
      analysis, high absolute lymphocyte count was the only risk factor for infusion
      related reaction (OR = 1.03; 95% CI: 1.01-1.06; p = 0.014). CONCLUSIONS:
      Rituximab infusion-related reactions in a heterogeneous pediatric population were
      frequent on first infusion, but rare in subsequent ones. Overall, these reactions
      were mild and manageable through pharmacological treatment. Patients with an
      elevated absolute lymphocyte count before infusion were at greater risk for an
      infusion-related reaction.

PMID- 29042840
TI  - Warfarin-Rifampin Drug Interaction in a Pediatric Patient.
AB  - Rifampin has been documented to significantly attenuate the effect of warfarin in
      adult patients. No data have been presented on the use of rifampin and warfarin
      in a pediatric patient. We report an extreme case of increased warfarin
      metabolism in a pediatric patient who was concomitantly receiving rifampin,
      despite receiving other medications that significantly decrease warfarin
      metabolism. The inhibitory effect of rifampin on warfarin therapy may be
      amplified in pediatric patients.

PMID- 29042841
TI  - Bradycardia in a Pediatric Heart Transplant Recipient: Is It the Sugammadex?
AB  - Sugammadex is a novel pharmacologic agent that is used to selectively reverse the
      effects of the neuromuscular blocking agents rocuronium and vecuronium. Various
      advantages have been reported when comparing its reversal of neuromuscular
      blockade to that achieved with acetylcholinesterase inhibitors (neostigmine). In
      heart transplant recipients, bradycardia may occur following the administration
      of acetylcholinesterase inhibitors, due to the denervation of the heart.
      Theoretically, the combination of rocuronium and sugammadex could be advantageous
      in this clinical scenario to avoid the potential bradycardia resulting from
      neostigmine administration. We present a 10-year-old male who developed profound
      bradycardia immediately following the administration of intravenous sugammadex.
      The options for reversal of neuromuscular blockade in heart transplant recipients
      is discussed, previous reports of bradycardia following sugammadex are presented,
      and the role of sugammadex in the bradycardia in our patient is reviewed.

PMID- 29042842
TI  - Bridging the Gap between Theory and Practice in Integrated Care: The Case of the
      Diabetic Foot Pathway in Tuscany.
AB  - INTRODUCTION AND BACKGROUND: As diabetic foot (DF) care benefits from
      integration, monitoring geographic variations in lower limb Major Amputation rate
      enables to highlight potential lack of Integrated Care. In Tuscany (Italy), these
      DF outcomes were good on average but they varied within the region. In order to
      stimulate an improvement process towards integration, the project aimed to shift
      health professionals' focus on the geographic variation issue, promote the
      Population Medicine approach, and engage professionals in a community of
      practice. METHOD: Three strategies were thus carried out: the use of a
      transparent performance evaluation system based on benchmarking; the use of
      patient stories and benchmarking analyses on outcomes, service utilization and
      costs that cross-checked delivery- and population-based perspectives; the
      establishment of a stable community of professionals to discuss data and
      practices. RESULTS: The project enabled professionals to shift their focus on
      geographic variation and to a joint accountability on outcomes and costs for the
      entire patient pathways. Organizational best practices and gaps in integration
      were identified and improvement actions towards Integrated Care were implemented.
      CONCLUSION AND DISCUSSION: For the specific category of care pathways whose
      geographic variation is related to a lack of Integrated Care, a comprehensive
      strategy to improve outcomes and reduce equity gaps by diffusing integration
      should be carried out.

PMID- 29042844
TI  - Designing a Care Pathway Model - A Case Study of the Outpatient Total Hip
      Arthroplasty Care Pathway.
AB  - INTRODUCTION: Although the clinical attributes of total hip arthroplasty (THA)
      care pathways have been thoroughly researched, a detailed understanding of the
      equally important organisational attributes is still lacking. The aim of this
      article is to contribute with a model of the outpatient THA care pathway that
      depicts how the care team should be organised to enable patient discharge on the
      day of surgery. THEORY: The outpatient THA care pathway enables patients to be
      discharged on the day of surgery, shortening the length of stay and intensifying
      the provision and organisation of care. We utilise visual care modelling to
      construct a visual design of the organisation of the care pathway. METHODS: An
      embedded case study was conducted of the outpatient THA care pathway at a
      teaching hospital in the Netherlands. The data were collected using a visual care
      modelling toolkit in 16 semi-structured interviews. Problems and inefficiencies
      in the care pathway were identified and addressed in the iterative design
      process. RESULTS: The results are two visual models of the most critical phases
      of the outpatient THA care pathway: diagnosis & preparation (1) and mobilisation
      & discharge (4). The results show the care team composition, critical value
      exchanges, and sequence that enable patient discharge on the day of surgery.
      CONCLUSION: The design addressed existing problems and is an optimisation of the
      case hospital's pathway. The network of actors consists of the patient (1),
      radiologist (1), anaesthetist (1), nurse specialist (1), pharmacist (1),
      orthopaedic surgeon (1,4), physiotherapist (1,4), nurse (4), doctor (4) and
      patient application (1,4). The critical value exchanges include patient
      preparation (mental and practical), patient education, aligned care team,
      efficient sequence of value exchanges, early patient mobilisation, flexible
      availability of the physiotherapist, functional discharge criteria, joint
      decision making and availability of the care team.

PMID- 29042843
TI  - The Development, Description and Appraisal of an Emergent Multimethod Research
      Design to Study Workforce Changes in Integrated Care Interventions.
AB  - INTRODUCTION: In this paper, we provide a detailed and explicit description of
      the processes and decisions underlying and shaping the emergent multimethod
      research design of our study on workforce changes in integrated chronic care.
      THEORY AND METHODS: The study was originally planned as mixed method research
      consisting of a preliminary literature review and quantitative check of these
      findings via a Delphi panel. However, when the findings of the literature review
      were not appropriate for quantitative confirmation, we chose to continue our
      qualitative exploration of the topic via qualitative questionnaires and secondary
      analysis of two best practice case reports. RESULTS: The resulting research
      design is schematically described as an emergent and interactive multimethod
      design with multiphase combination timing. In doing so, we provide other
      researchers with a set of theory- and experience-based options to develop their
      own multimethod research and provide an example for more detailed and structured
      reporting of emergent designs. CONCLUSION AND DISCUSSION: We argue that the
      terminology developed for the description of mixed methods designs should also be
      used for multimethod designs such as the one presented here.

PMID- 29042845
TI  - Implementation of Integrated Service Networks under the Quebec Mental Health
      Reform: Facilitators and Barriers associated with Different Territorial Profiles.
AB  - INTRODUCTION: This study evaluates implementation of the Quebec Mental Health
      Reform (2005-2015), which promoted the development of integrated service
      networks, in 11 local service networks organized into four territorial groups
      according to socio-demographic characteristics and mental health services
      offered. METHODS: Data were collected from documents concerning networks;
      structured questionnaires completed by 90 managers and by 16 respondent
      psychiatrists; and semi-structured interviews with 102 network stakeholders.
      Factors associated with implementation and integration were organized according
      to: 1) reform characteristics; 2) implementation context; 3) organizational
      characteristics; and 4) integration strategies. RESULTS: While local networks
      were in a process of development and expansion, none were fully integrated at the
      time of the study. Facilitators and barriers to implementation and integration
      were primarily associated with organizational characteristics. Integration was
      best achieved in larger networks including a general hospital with a psychiatric
      department, followed by networks with a psychiatric hospital. Formalized
      integration strategies such as service agreements, liaison officers, and joint
      training reduced some barriers to implementation in networks experiencing less
      favourable conditions. CONCLUSION: Strategies for the implementation of
      healthcare reform and integrated service networks should include sustained
      support and training in best-practices, adequate performance indicators and
      resources, formalized integration strategies to improve network coordination and
      suitable initiatives to promote staff retention.

PMID- 29042846
TI  - Developing a User Reported Measure of Care Co-ordination.
AB  - INTRODUCTION: Older people with chronic conditions often receive poor care
      because of the fragmented way in which their services are delivered from multiple
      sources. Providers have limited tools to directly capture the views of older
      people about their experiences of care co-ordination. The study aim was to design
      and test a survey tool to capture the experiences of older people with chronic
      conditions regarding how well their health and (where applicable) social care was
      co-ordinated. METHOD: To inform the questionnaire development, we reviewed the
      literature on existing surveys and care co-ordination theory, and on the health
      status of our target audience (people aged 65 or over with one or more chronic
      conditions and not in hospital or residential institutions). We also consulted
      stakeholders including those working in health and social care services and those
      with expertise in the subject area. We grouped questions around experiences of
      care in three dimensions: care in the home environment, planned transitions in
      care and unplanned situations. We also designed the questions so they could be
      mapped onto three recognised dimensions of continuity of care - management
      continuity, information continuity and relational continuity - as articulated in
      the international literature. The questionnaire was tested using focus groups and
      cognitive interviews and piloted with people aged 65 and over with at least one
      chronic condition, using a postal survey. We used service user records in 32
      general practices located in four areas and a population database held by one
      local authority in England as the sampling frame. RESULTS: The pilot achieved an
      overall response rate of 27.6% (n = 562 responses). Ninety five percent of
      respondents answered 30 or more of the 46 questions and three respondents
      answered fewer than 10 questions. Twenty four items achieved one or more positive
      correlations greater than 0.5 with other survey items and four instances of
      positive associations greater than 0.7 were found. DISCUSSION/CONCLUSION: The
      growing focus on care co-ordination demonstrates the need for a tool that can
      capture the experiences of patients accessing care across organisational and
      professional boundaries, to inform the improvement of care co-ordination
      activities from a patient perspective. Early results suggest that our tool may
      have a contribution to make in these areas. However, more work is required to
      test the efficacy of the tool on a larger scale and in different settings, and to
      find ways of improving response rates.

PMID- 29042847
TI  - An Enquiry into Nurse-to-Nurse Collaboration Within the Older People Care Chain
      as Part of the Integrated Care: A Qualitative Study.
AB  - INTRODUCTION: Health care systems for older people are becoming more complex and
      care for older people, in the transition between hospital and primary healthcare
      requires more systematic collaboration between nurses. This study describes
      nurses' perceptions of their collaboration when working between hospital and
      primary healthcare within the older people care chain. THEORY AND METHODS: Using
      a qualitative approach, informed by grounded theory, six focus groups were
      conducted with a purposive sample of registered nurses (n = 28) from hospitals (n
      = 14) and primary healthcare (n = 14) during 2013. The data were analyzed using
      dimensional analysis. FINDINGS: Four dimensions of collaboration were identified:
      1) Context and Situation, 2) Conditions, 3) Processes and Interactions and 4) The
      Consequences of nurse-to-nurse collaboration within the older people care chain.
      These four dimensions were then conceptualized into a model of nurse-to-nurse
      collaboration. DISCUSSION AND CONCLUSION: Improved collaboration is useful for
      the safe, timely and controlled transfer of older people between hospital and
      primary healthcare organizations and also in healthcare education. The findings
      in this study of nurse-to-nurse collaboration provides direction and
      opportunities to improve collaboration and subsequently, the continuity and
      integration in older people care in the transition between organizations.

PMID- 29042848
TI  - Integrated Diabetes Care Delivered by Patients - A Case Study from Bulgaria.
AB  - INTRODUCTION: Increasing numbers of persons are living with multiple chronic
      diseases and unmet medical needs in Bulgaria. The Bulgarian 'Diabetic care' non
      profit (DCNPO) programme aims to provide comprehensive integrated care focusing
      on people with diabetes and their co-morbidities. METHODS: The DCNPO programme
      was selected as one of eight 'high potential' programmes in the Innovating Care
      for People with Multiple Chronic Conditions (ICARE4EU) project, covering 31
      European countries. Data was first gathered with a questionnaire after which semi
      structured interviews with project staff and participants were conducted during a
      site visit. RESULTS: The programme trains diabetic patients to act as carers,
      case managers, self-management trainers and health system navigators for diabetic
      patients and their family. The programme improved care coordination and patient
      centered care by offering free care delivered by a multidisciplinary team. It
      facilitates the collaboration between patients, volunteers, health providers and
      the community. Internal evaluations demonstrate reduced hospital admissions and
      avoidable amputations, with consequent cost savings for the health care system.
      CONCLUSION: Integrated care provided by volunteering patients can empower people
      suffering from diabetes and their co-morbidities and address health and social
      inequalities in resource-poor settings. It can also contribute to an increased
      trust and improved satisfaction among vulnerable patients with complex care
      needs.

PMID- 29042850
TI  - More than Just a Narrative: Measuring People's Experience of Care Coordination to
      Improve Quality and Outcomes.

PMID- 29042849
TI  - Does Coordinated Postpartum Care Influence Costs?
AB  - QUESTIONS UNDER STUDY: To investigate changes to health insurance costs for post
      discharge postpartum care after the introduction of a midwife-led coordinated
      care model. METHODS: The study included mothers and their newborns insured by the
      Helsana health insurance group in Switzerland and who delivered between January
      2012 and May 2013 in the canton of Basel Stadt (BS) (intervention canton). We
      compared monthly post-discharge costs before the launch of a coordinated
      postpartum care model (control phase, n = 144) to those after its introduction
      (intervention phase, n = 92). Costs in the intervention canton were also compared
      to those in five control cantons without a coordinated postpartum care model
      (cross-sectional control group: n = 7, 767). RESULTS: The average monthly post
      discharge costs for mothers remained unchanged in the seven months following the
      introduction of a coordinated postpartum care model, despite a higher use of
      midwife services (increasing from 72% to 80%). Likewise, monthly costs did not
      differ between the intervention canton and five control cantons. In multivariate
      analyses, the ambulatory costs for mothers were not associated with the post
      intervention phase. Cross-sectionally, however, they were positively associated
      with midwifery use. For children, costs in the post-intervention phase were lower
      in the first month after hospital discharge compared to the pre-intervention
      phase (difference of -114 CHF [95%CI -202 CHF to -27 CHF]), yet no differences
      were seen in the cross-sectional comparison. CONCLUSIONS: The introduction of a
      coordinated postpartum care model was associated with decreased costs for
      neonates in the first month after hospital discharge. Despite increased midwifery
      use, costs for mothers remained unchanged.

PMID- 29042851
TI  - Implementing Information and Communication Technology to Support Community Aged
      Care Service Integration: Lessons from an Australian Aged Care Provider.
AB  - INTRODUCTION: There is limited evidence of the benefits of information and
      communication technology (ICT) to support integrated aged care services.
      OBJECTIVES: We undertook a case study to describe carelink+, a centralised client
      service management ICT system implemented by a large aged and community care
      service provider, Uniting. We sought to explicate the care-related information
      exchange processes associated with carelink+ and identify lessons for
      organisations attempting to use ICT to support service integration. METHODS: Our
      case study included seventeen interviews and eleven observation sessions with a
      purposive sample of staff within the organisation. Inductive analysis was used to
      develop a model of ICT-supported information exchange. RESULTS: Management staff
      described the integrated care model designed to underpin carelink+. Frontline
      staff described complex information exchange processes supporting coordination of
      client services. Mismatches between the data quality and the functions carelink+
      was designed to support necessitated the evolution of new work processes
      associated with the system. CONCLUSIONS: There is value in explicitly modelling
      the work processes that emerge as a consequence of ICT. Continuous evaluation of
      the match between ICT and work processes will help aged care organisations to
      achieve higher levels of ICT maturity that support their efforts to provide
      integrated care to clients.

PMID- 29042852
TI  - Corrigendum: Obesity and Co-morbid Conditions Are Associated with Specific
      Neuropsychiatric Symptoms in Mild Cognitive Impairment.
AB  - [This corrects the article on p. 164 in vol. 9, PMID: 28611655.].

PMID- 29042853
TI  - Corrigendum: An Exploration of Charge Compensating Ion Channels across the
      Phagocytic Vacuole of Neutrophils.
AB  - [This corrects the article on p. 94 in vol. 8, PMID: 28293191.].

PMID- 29042854
TI  - Influence of Standard Laboratory Procedures on Measures of Erythrocyte Damage.
AB  - The ability to characterize the mechanical properties of erythrocytes is
      important in clinical and research contexts: to diagnose and monitor hematologic
      disorders, as well as to optimize the design of cardiovascular implants and blood
      circulating devices with respect to blood damage. However, investigation of red
      blood cell (RBC) properties generally involves preparatory and processing steps.
      Even though these impose mechanical stresses on cells, little is known about
      their impact on the final measurement results. In this study, we investigated the
      effect of centrifuging, vortexing, pipetting, and high pressures on several
      markers of mechanical blood damage and RBC membrane properties. Using human
      venous blood, we analyzed erythrocyte damage by measuring free hemoglobin,
      phosphatidylserine exposure by flow cytometry, RBC deformability by ektacytometry
      and the parameters of a complete blood count. We observed increased levels of
      free hemoglobin for all tested procedures. The release of hemoglobin into plasma
      depended significantly on the level of stress. Elevated pressures and
      centrifuging also altered mean cell volume (MCV) and mean corpuscular hemoglobin
      (MCH), suggesting changes in erythrocyte population, and membrane properties. Our
      results show that the effects of blood handling can significantly influence
      erythrocyte damage metrics. Careful quantification of this influence as well as
      other unwanted secondary effects should thus be included in experimental
      protocols and accounted for in clinical laboratories.

PMID- 29042855
TI  - Corrigendum: FVB/NJ Mice Are a Useful Model for Examining Cardiac Adaptations to
      Treadmill Exercise.
AB  - [This corrects the article on p. 636 in vol. 7, PMID: 28066267.].

PMID- 29042856
TI  - The Utility of a Computerized Algorithm Based on a Multi-Domain Profile of
      Measures for the Diagnosis of Attention Deficit/Hyperactivity Disorder.
AB  - The current gold standard for diagnosis of attention deficit/hyperactivity
      disorder (ADHD) includes subjective measures, such as clinical interview,
      observation, and rating scales. The significant heterogeneity of ADHD symptoms
      represents a challenge for this assessment and could prevent an accurate
      diagnosis. The aim of this work was to investigate the ability of a multi-domain
      profile of measures, including blood fatty acid (FA) profiles, neuropsychological
      measures, and functional measures from near-infrared spectroscopy (fNIRS), to
      correctly recognize school-aged children with ADHD. To answer this question, we
      elaborated a supervised machine-learning method to accurately discriminate 22
      children with ADHD from 22 children with typical development by means of the
      proposed profile of measures. To assess the performance of our classifier, we
      adopted a nested 10-fold cross validation, where the original dataset was split
      into 10 subsets of equal size, which were used repeatedly for training and
      testing. Each subset was used once for performance validation. Our method reached
      a maximum diagnostic accuracy of 81% through the combining of the predictive
      models trained on neuropsychological, FA profiles, and deoxygenated-hemoglobin
      features. With respect to the analysis of a single-domain dataset per time, the
      most discriminant neuropsychological features were measures of vigilance, focused
      and sustained attention, and cognitive flexibility; the most discriminating blood
      FAs were linoleic acid and the total amount of polyunsaturated fatty acids.
      Finally, with respect to the fNIRS data, we found a significant advantage of the
      deoxygenated-hemoglobin over the oxygenated-hemoglobin data in terms of
      predictive accuracy. These preliminary findings show the feasibility and
      applicability of our machine-learning method in correctly identifying children
      with ADHD based on multi-domain data. The present machine-learning classification
      approach might be helpful for supporting the clinical practice of diagnosing
      ADHD, even fostering a computer-aided diagnosis perspective.

PMID- 29042857
TI  - Clinical Implications of Associations between Headache and Gastrointestinal
      Disorders: A Study Using the Hallym Smart Clinical Data Warehouse.
AB  - BACKGROUND: The brain and gastrointestinal (GI) tract are strongly connected via
      neural, endocrine, and immune pathways. Previous studies suggest that headaches,
      especially migraines, may be associated with various GI disorders. However, upper
      GI endoscopy in migraineurs has shown a low prevalence of abnormal findings.
      Also, the majority of studies have not demonstrated an association between
      Helicobacter pylori (HP) infection and migraine, although a pathogenic role for
      HP infection in migraines has been suggested. Further knowledge concerning the
      relation between headaches and GI disorders is important as it may have
      therapeutic consequences. Thus, we sought to investigate possible associations
      between GI disorders and common primary headaches, such as migraines and tension
      type headaches (TTH), using the Smart Clinical Data Warehouse (CDW) over a period
      of 10 years. METHODS: We retrospectively investigated clinical data using a
      clinical data analytic solution called the Smart CDW from 2006 to 2016. In
      patients with migraines and TTH who visited a gastroenterology center, GI
      disorder diagnosis, upper GI endoscopy findings, and results of HP infection were
      collected and compared to clinical data from controls, who had health checkups
      without headache. The time interval between headache diagnosis and an examination
      at a gastroenterology center did not exceed 1 year. RESULTS: Patients were age-
      and sex-matched and eligible cases were included in the migraine (n = 168), the
      TTH (n = 168), and the control group (n = 336). Among the GI disorders diagnosed
      by gastroenterologists, gastroesophageal reflux disorder was more prevalent in
      the migraine group, whereas gastric ulcers were more common in the migraine and
      TTH groups compared with controls (p < 0.0001). With regard to endoscopic
      findings, there were high numbers of erosive gastritis and chronic superficial
      gastritis cases in the migraine and TTH groups, respectively, and the severity of
      gastritis was significantly higher in patients with TTH compared with controls (p
      < 0.001). However, no differences were observed in the prevalence of HP infection
      between the groups. CONCLUSION: The observed association in this study may
      suggest that primary headache sufferers who experience migraines or TTH are more
      prone to GI disorders, which may have various clinical implications. Further
      research concerning the etiology of the association between headaches and GI
      disorders is warranted.

PMID- 29042858
TI  - Expanding the Role of Thyroid-Stimulating Hormone in Skeletal Physiology.
AB  - The dogma that thyroid-stimulating hormone (TSH) solely regulates the production
      of thyroid hormone from the thyroid gland has hampered research on its wider
      physiological roles. The action of pituitary TSH on the skeleton has now been
      well described; in particular, its action on osteoblasts and osteoclasts. It has
      also been recently discovered that the bone marrow microenvironment acts as an
      endocrine circuit with bone marrow-resident macrophages capable of producing a
      novel TSH-beta subunit variant (TSH-betav), which may modulate skeletal
      physiology. Interestingly, the production of this TSH-betav is positively
      regulated by T3 accentuating such modulation in the presence of thyroid
      overactivity. Furthermore, a number of small molecule ligands acting as TSH
      agonists, which allosterically modulate the TSH receptor have been identified and
      may have similar modulatory influences on bone cells suggesting therapeutic
      potential. This review summarizes our current understanding of the role of TSH,
      TSH-beta, TSH-betav, and small molecule agonists in bone physiology.

PMID- 29042859
TI  - Associations between Systemic Sclerosis and Thyroid Diseases.
AB  - We have reviewed scientific literature about the association of systemic
      sclerosis (SSc) and thyroid disorders. A high incidence, and prevalence, of new
      cases of autoimmune thyroiditis (AT) and/or hypothyroidism have been shown in
      sclerodermic patients (overall in the female gender). An association among a Th1
      immune-predominance, low vitamin D levels, and AT have been also shown in SSc
      patients. Cases of Graves' disease (GD) have been described in SSc patients, too,
      according with the higher prevalence of thyroid autoimmunity. It has been also
      shown a higher prevalence of papillary thyroid cancer (PTC), in association with
      AT, in SSc patients. However, in order to confirm results about GD and thyroid
      cancer, studies in larger number of patients with SSc are needed. During the
      follow-up of SSc patients it would be appropriate to monitor carefully their
      thyroid status. The abovementioned data strongly suggest a periodic thyroid
      function follow-up in female SSc patients [showing a borderline high (although in
      the normal range) thyroid-stimulating hormone level, antithyroid peroxidase
      antibody positivity, and a small thyroid with a hypoechoic pattern], and, when
      necessary, appropriate treatments. In conclusion, most of the studies show an
      association among SSc, AT, and hypothyroidism, such as an increased prevalence of
      TC overall in SSc patients with AT. Only few cases of GD have been also described
      in SSc.

PMID- 29042860
TI  - Toll-Like Receptor 8 Is a Major Sensor of Group B Streptococcus But Not
      Escherichia coli in Human Primary Monocytes and Macrophages.
AB  - TLR8 is the major endosomal sensor of degraded RNA in human monocytes and
      macrophages. It has been implicated in the sensing of viruses and more recently
      also bacteria. We previously identified a TLR8-IFN regulatory factor 5 (IRF5)
      signaling pathway that mediates IFNbeta and interleukin-12 (IL-12) induction by
      Staphylococcus aureus and is antagonized by TLR2. The relative importance of TLR8
      for the sensing of various bacterial species is however still unclear. We here
      compared the role of TLR8 and IRF5 for the sensing of Group B Streptococcus
      (GBS), S. aureus, and Escherichia coli in human primary monocytes and monocyte
      derived macrophages (MDM). GBS induced stronger IFNbeta and TNF production as
      well as IRF5 nuclear translocation compared to S. aureus grown to the stationary
      phase, while S. aureus in exponential growth appeared similarly potent to GBS.
      Cytokine induction in primary human monocytes by GBS was not dependent on
      hemolysins, and induction of IFNbeta and IL-12 as well as IRF5 activation were
      reduced with TLR2 ligand costimulation. Heat inactivation of GBS reduced IRF5 and
      NF-kB translocation, while only the viable E. coli activated IRF5. The attenuated
      stimulation correlated with loss of bacterial RNA integrity. The E. coli-induced
      IRF5 translocation was not inhibited by TLR2 costimulation, suggesting that IRF5
      was activated via a TLR8-independent mechanism. Gene silencing of MDM using siRNA
      revealed that GBS-induced IFNbeta, IL-12-p35, and TNF production was dependent on
      TLR8 and IRF5. In contrast, cytokine induction by E. coli was TLR8 independent
      but still partly dependent on IRF5. We conclude that TLR8-IRF5 signaling is more
      important for the sensing of GBS than for stationary grown S. aureus in human
      primary monocytes and MDM, likely due to reduced resistance of GBS to phagosomal
      degradation and to a lower production of TLR2 activating lipoproteins. TLR8 does
      not sense viable E. coli, while IRF5 still contributes to E. coli-induced
      cytokine production, possibly via a cytosolic nucleic acid sensing mechanism.

PMID- 29042862
TI  - Highly Efficient Single-Step Enrichment of Low Abundance Phosphopeptides from
      Plant Membrane Preparations.
AB  - Mass spectrometry (MS)-based large scale phosphoproteomics has facilitated the
      investigation of plant phosphorylation dynamics on a system-wide scale. However,
      generating large scale data sets for membrane phosphoproteins usually requires
      fractionation of samples and extended hands-on laboratory time. To overcome these
      limitations, we developed "ShortPhos," an efficient and simple phosphoproteomics
      protocol optimized for research on plant membrane proteins. The optimized
      workflow allows fast and efficient identification and quantification of
      phosphopeptides, even from small amounts of starting plant materials. "ShortPhos"
      can produce label-free datasets with a high quantitative reproducibility. In
      addition, the "ShortPhos" protocol recovered more phosphorylation sites from
      membrane proteins, especially plasma membrane and vacuolar proteins, when
      compared to our previous workflow and other membrane-based data in the PhosPhAt
      4.0 database. We applied "ShortPhos" to study kinase-substrate relationships
      within a nitrate-induction experiment on Arabidopsis roots. The "ShortPhos"
      identified significantly more known kinase-substrate relationships compared to
      previous phosphoproteomics workflows, producing new insights into nitrate-induced
      signaling pathways.

PMID- 29042863
TI  - Adult reference intervals for IgG subclasses with Siemens immunonephelometric
      assays in Chinese population.
AB  - OBJECTIVE: To determine the adult reference intervals for the Siemens IgG
      subclass reagents. METHODS: 636 blood samples of healthy adults were analyzed to
      determine the level of IgG subclass using the reagents of Siemens
      immunonephelometric assay with molecular biology kits. RESULTS: IgGSc reference
      intervals were as follows: IgG1 4.45-9.76 g/L, IgG2 2.07-8.57 g/L, IgG3 0.08-0.80
      g/L and IgG4 0.05-1.54 g/L. There was an excellent correlation between the total
      IgG and the sum of the IgG subclasses. No significant gender and age differences
      were observed. CONCLUSIONS: Our data provide the missing reference intervals and
      enable the use of the nephelometric IgG subclass reagents in Chinese. The study
      can offer reference on clinic diagnose.

PMID- 29042861
TI  - Corrigendum: Natural Killer Cells from Patients with Recombinase-Activating Gene
      and Non-Homologous End Joining Gene Defects Comprise a Higher Frequency of
      CD56bright NKG2A+++ Cells, and Yet Display Increased Degranulation and Higher
      Perforin Content.
AB  - [This corrects the article on p. 798 in vol. 8, PMID: 28769923.].

PMID- 29042864
TI  - Recent advances in pediatric interventional cardiology.
AB  - During the last 10 years, there have been major technological achievements in
      pediatric interventional cardiology. In addition, there have been several
      advances in cardiac imaging, especially in 3-dimensional imaging of
      echocardiography, computed tomography, magnetic resonance imaging, and
      cineangiography. Therefore, more types of congenital heart diseases can be
      treated in the cardiac catheter laboratory today than ever before. Furthermore,
      lesions previously considered resistant to interventional therapies can now be
      managed with high success rates. The hybrid approach has enabled the overcoming
      of limitations inherent to percutaneous access, expanding the application of
      endovascular therapies as adjunct to surgical interventions to improve patient
      outcomes and minimize invasiveness. Percutaneous pulmonary valve implantation has
      become a successful alternative therapy. However, most of the current
      recommendations about pediatric cardiac interventions (including class I
      recommendations) refer to off-label use of devices, because it is difficult to
      study the safety and efficacy of catheterization and transcatheter therapy in
      pediatric cardiac patients. This difficulty arises from the challenge of
      identifying a control population and the relatively small number of pediatric
      patients with congenital heart disease. Nevertheless, the pediatric
      interventional cardiology community has continued to develop less invasive
      solutions for congenital heart defects to minimize the need for open heart
      surgery and optimize overall outcomes. In this review, various interventional
      procedures in patients with congenital heart disease are explored.

PMID- 29042865
TI  - Additional corticosteroids or alternative antibiotics for the treatment of
      macrolide-resistant Mycoplasma pneumoniae pneumonia.

PMID- 29042866
TI  - Effects of cord blood vitamin D levels on the risk of neonatal sepsis in
      premature infants.
AB  - PURPOSE: Vitamin D plays a key role in immune function. Vitamin D deficiency may
      play a role in the pathogenesis of infections, and low levels of circulating
      vitamin D are strongly associated with infectious diseases. In this study, we
      aimed to evaluate the effects of low vitamin D levels in cord blood on neonatal
      sepsis in preterm infants. METHODS: One hundred seventeen premature infants with
      gestational age of <37 weeks were enrolled. In the present study, severe vitamin
      D deficiency (group 1) was defined as a 25-hydroxyvitamin D (25(OH)D)
      concentration <5 ng/mL; vitamin D insufficiency (group 2), 25(OH)D concentration
      >=5 ng/mL and <15 ng/mL; and vitamin D sufficiency (group 3), 25(OH)D
      concentration >=15 ng/mL. RESULTS: Sixty-three percent of the infants had
      deficient levels of cord blood vitamin D (group 1), 24% had insufficient levels
      (group 2), and 13% were found to have sufficient levels (group 3). The rate of
      neonatal sepsis was higher in group 2 than in groups 1 and 3. CONCLUSION: There
      was no significant relationship between the cord blood vitamin D levels and the
      risk of neonatal sepsis in premature infants.

PMID- 29042867
TI  - The impact of an educational intervention on parents' decisions to vaccinate
      their <60-month-old children against influenza.
AB  - PURPOSE: Seasonal influenza can be prevented by vaccination. Disease prevention
      in children aged <60 months is of particular importance because of the associated
      familial and societal burden. Considering that caretakers make the decision to
      vaccinate their children, the identification of drivers and barriers to
      vaccination is essential to increase influenza vaccination coverage. METHODS: A
      total of 639 parents participated in the pre- and posteducational survey and 450
      parents participated in the study via telephone interviews. The participating
      parents were asked to rank their agreement with each statement of the survey
      questionnaire on a scale from 1 (strongly disagree) to 5 (strongly agree), and
      the scores between pre- and postintervention were compared. RESULTS: Before the
      educational intervention, 105 out of 639 participants reported not to agree to
      vaccinate their children against influenza. After the intervention, 46 out of the
      105 parents changed their opinions about childhood vaccination. The physicians'
      recommendation received the highest agreement score and was the most important
      driver to vaccination, whereas the cost of vaccination was the strongest factor
      for not vaccinating children. In general, the participants significantly changed
      the agreement scores between pre- and postintervention. However, the unfavorable
      opinions about vaccination and the convenience of receiving the influenza vaccine
      did not change significantly. CONCLUSION: The results of this study indicate that
      a specific educational intervention involving caregivers is very effective in
      increasing the influenza vaccination coverage of children aged less than 60
      months.

PMID- 29042868
TI  - Characteristics and prognosis of hepatic cytomegalovirus infection in children:
      10 years of experience at a university hospital in Korea.
AB  - PURPOSE: Studies on cytomegalovirus (CMV) infections in immunocompetent children
      are lacking, and minimal information is available in the medical literature on
      hepatic manifestations and complications of CMV. The aims of this study were to
      evaluate the clinical characteristics, laboratory data, and prognosis of children
      with CMV hepatitis, and to investigate its prevalence at a single medical center
      in Korea over a 10-year period. METHODS: One hundred thirty-two children
      diagnosed with CMV infection based on specific markers (anti-CMV IgM, CMV
      polymerase chain reaction in blood and urine, or CMV culture of urine) were
      included in the study. Clinical and biochemical characteristics, immunological
      markers, and outcomes of hepatic CMV infection were determined. RESULTS: The
      median age of patients (n=132) was 8.5 months (range, 14 days-11.3 years). Peak
      total bilirubin and alanine aminotransferase levels in serum ranged from 0.11
      21.97 mg/dL, and 5-1,517 IU/L, respectively. Alanine aminotransferase remained
      elevated from 2-48 weeks. Jaundice was the most common clinical feature of
      hepatic CMV infection during infancy. The hematologic findings revealed anemia,
      leukocytosis, and monocytosis in CMV-infected patients. All participants
      recovered without administration of ganciclovir. CONCLUSION: In children with CMV
      hepatitis, fever was the most common symptom at presentation, and jaundice was
      the most common clinical feature of hepatic CMV infection in infants younger than
      3 months of age. Hepatic CMV infection in immunocompetent children is often a
      self-limited illness that does not require antiviral therapy, as most patients in
      this study had favorable outcomes.

PMID- 29042869
TI  - Clinical characteristics of hypertensive encephalopathy in pediatric patients.
AB  - PURPOSE: The aim of this study was to assess the clinical characteristics of
      hypertensive encephalopathy according to the underlying etiologies in children.
      METHODS: We retrospectively evaluated 33 pediatric patients who were diagnosed as
      having hypertensive encephalopathy in Chonbuk National University Children's
      Hospital. Among the patients, 18 were excluded because of incomplete data or
      because brain magnetic resonance imaging (MRI) was not performed. Finally, 17
      patients were enrolled and divided into a renal-origin hypertension group and a
      non-renal-origin hypertension group according to the underlying cause. We
      compared the clinical features and brain MRI findings between the 2 groups.
      RESULTS: The renal group included renal artery stenosis (4), acute
      poststreptococcal glomerulonephritis (2), lupus nephritis (2), and acute renal
      failure (1); the nonrenal group included essential hypertension (4),
      pheochromocytoma (2), thyrotoxicosis (1), and acute promyelocytic leukemia (1).
      The mean systolic blood pressure of the renal group (172.5+/-36.9 mmHg) was
      higher than that of the nonrenal group (137.1+/-11.1 mmHg, P<0.05). Seizure was
      the most common neurologic symptom, especially in the renal group (P<0.05).
      Posterior reversible encephalopathy syndrome (PRES), which is the most typical
      finding of hypertensive encephalopathy, was found predominantly in the renal
      group as compared with the nonrenal group (66.6% vs. 12.5%, P<0.05). CONCLUSION:
      We conclude that the patients with renal-origin hypertension had a more severe
      clinical course than those with non-renal-origin hypertension. Furthermore, the
      renal-origin group was highly associated with PRES on brain MRI.

PMID- 29042870
TI  - Update of minimally invasive surfactant therapy.
AB  - To date, preterm infants with respiratory distress syndrome (RDS) after birth
      have been managed with a combination of endotracheal intubation, surfactant
      instillation, and mechanical ventilation. It is now recognized that noninvasive
      ventilation (NIV) such as nasal continuous positive airway pressure (CPAP) in
      preterm infants is a reasonable alternative to elective intubation after birth.
      Recently, a meta-analysis of large controlled trials comparing conventional
      methods and nasal CPAP suggested that CPAP decreased the risk of the combined
      outcome of bronchopulmonary dysplasia or death. Since then, the use of NIV as
      primary therapy for preterm infants has increased, but when and how to give
      exogenous surfactant remains unclear. Overcoming this problem, minimally invasive
      surfactant therapy (MIST) allows spontaneously breathing neonates to remain on
      CPAP in the first week after birth. MIST has included administration of exogenous
      surfactant by intrapharyngeal instillation, nebulization, a laryngeal mask, and a
      thin catheter. In recent clinical trials, surfactant delivery via a thin catheter
      was found to reduce the need for subsequent endotracheal intubation and
      mechanical ventilation, and improves short-term respiratory outcomes. There is
      also growing evidence for MIST as an alternative to the INSURE (intubation
      surfactant-extubation) procedure in spontaneously breathing preterm infants with
      RDS. In conclusion, MIST is gentle, safe, feasible, and effective in preterm
      infants, and is widely used for surfactant administration with noninvasive
      respiratory support by neonatologists. However, further studies are needed to
      resolve uncertainties in the MIST method, including infant selection, optimal
      surfactant dosage and administration method, and need for sedation.

PMID- 29042871
TI  - Application of array comparative genomic hybridization in Korean children under 6
      years old with global developmental delay.
AB  - PURPOSE: Recent advancements in molecular techniques have greatly contributed to
      the discovery of genetic causes of unexplained developmental delay. Here, we
      describe the results of array comparative genomic hybridization (CGH) and the
      clinical features of 27 patients with global developmental delay. METHODS: We
      included 27 children who fulfilled the following criteria: Korean children under
      6 years with global developmental delay; children who had at least one or more
      physical or neurological problem other than global developmental delay; and
      patients in whom both array CGH and G-banded karyotyping tests were performed.
      RESULTS: Fifteen male and 12 female patients with a mean age of 29.3+/-17.6
      months were included. The most common physical and neurological abnormalities
      were facial dysmorphism (n=16), epilepsy (n=7), and hypotonia (n=7). Pathogenic
      copy number variation results were observed in 4 patients (14.8%): 18.73 Mb
      dup(2)(p24.2p25.3) and 1.62 Mb del(20p13) (patient 1); 22.31 Mb dup(2)
      (p22.3p25.1) and 4.01 Mb dup(2)(p21p22.1) (patient 2); 12.08 Mb del(4)(q22.1q24)
      (patient 3); and 1.19 Mb del(1)(q21.1) (patient 4). One patient (3.7%) displayed
      a variant of uncertain significance. Four patients (14.8%) displayed discordance
      between G-banded karyotyping and array CGH results. Among patients with normal
      array CGH results, 4 (16%) revealed brain anomalies such as schizencephaly and
      hydranencephaly. One patient was diagnosed with Rett syndrome and one with Mobius
      syndrome. CONCLUSION: As chromosomal microarray can elucidate the cause of
      previously unexplained developmental delay, it should be considered as a first
      tier cytogenetic diagnostic test for children with unexplained developmental
      delay.

PMID- 29042872
TI  - Accuracy of maximal expiratory flow-volume curve curvilinearity and fractional
      exhaled nitric oxide for detection of children with atopic asthma.
AB  - PURPOSE: Airway pathology in children with atopic asthma can be reflected by the
      concave shape of the maximal expiratory flow-volume (MEFV) curve and high
      fractional exhaled nitric oxide (FeNO) values. We evaluated the capacity of the
      curvilinearity of the MEFV curve, FeNO, and their combination to distinguish
      subjects with atopic asthma from healthy individuals. METHODS: FeNO and angle
      beta, which characterizes the general configuration of the MEFV curve, were
      determined in 119 steroid-naive individuals with atopic asthma aged 8 to 16
      years, and in 92 age-matched healthy controls. Receiver operating characteristic
      (ROC) curve analyses were performed to determine the cutoff points of FeNO and
      angle beta that provided the best combination of sensitivity and specificity for
      asthma detection. RESULTS: Asthmatic patients had a significantly smaller angle
      beta and higher FeNO compared with healthy controls (both, P<0.001). For asthma
      detection, the best cutoff values of angle beta and FeNO were observed at 189.3
      degrees  and 22 parts per billion, respectively. The area under the ROC curve for
      the combination of angle beta and FeNO improved to 0.91 (95% confidence interval
      [CI], 0.87-0.95) from 0.80 (95% CI, 0.75-0.86; P<0.001) for angle beta alone and
      0.86 (95% CI, 0.82-0.91; P=0.002) for FeNO alone. In addition, the combination
      enhanced sensitivity with no significant decrease in specificity. CONCLUSION:
      These data suggest that the combined use of the curvilinearity of the MEFV curve
      and FeNO is a useful tool to differentiate between children with and without
      atopic asthma.

PMID- 29042873
TI  - Comparison of cytokine expression profiles in infants with a rhinovirus induced
      lower respiratory tract infection with or without wheezing: a comparison with
      respiratory syncytial virus.
AB  - PURPOSE: The aim of this study was to evaluate whether infants with rhinovirus
      (RV) infection-induced wheezing and those with respiratory syncytial virus (RSV)
      infection-induced wheezing have different cytokine profiles in the acute stage.
      METHODS: Of the infants with lower respiratory tract infection (LRTI) between
      September 2011 and May 2012, 88 were confirmed using reverse transcription
      polymerase chain reaction and hospitalized. Systemic interferon-gamma (IFN
      gamma), interleukin (IL)-2, IL-12, IL-4, IL-5, IL-13, and Treg-type cytokine (IL
      10) responses were examined with multiplex assay using acute phase serum samples.
      RESULTS: Of the 88 patients, 38 had an RV infection (RV group) and 50 had an RSV
      infection (RSV group). In the RV group, the IFN-gamma and IL-10 concentrations
      were higher in the patients with than in the patients without wheezing (P=0.022
      and P=0.007, respectively). In the RSV group, the differences in IFN-gamma and IL
      10 concentrations did not reach statistical significance between the patients
      with and the patients without wheezing (P=0.105 and P=0.965, respectively). The
      IFN-gamma and IL-10 concentrations were not significantly different between the
      RV group with wheezing and the RSV group with wheezing (P=0.155 and P=0.801,
      respectively), in contrast to the significant difference between the RV group
      without wheezing and the RSV group without wheezing (P=0.019 and P=0.035,
      respectively). CONCLUSION: In comparison with RSV-induced LRTI, RV-induced LRTI
      combined with wheezing showed similar IFN-gamma and IL-10 levels, which may have
      an important regulatory function.

PMID- 29042874
TI  - Serum neuron specific enolase is increased in pediatric acute encephalitis
      syndrome.
AB  - PURPOSE: This study aimed to investigate whether serum neuron-specific enolase
      (NSE) was expressed in acute encephalitis syndrome (AES) that causes neuronal
      damage in children. METHODS: This prospective observational study was conducted
      in the pediatric neurology ward of Soetomo Hospital. Cases of AES with ages
      ranging from 1 month to 12 years were included. Cases that were categorized as
      simple and complex febrile seizures constituted the non-AES group. Blood was
      collected for the measurement of NSE within 24 hours of hemodynamic
      stabilization. The median NSE values of both groups were compared by using the
      Mann-Whitney U test. All statistical analyses were performed with SPSS version 12
      for Windows. RESULTS: In the study period, 30 patients were enrolled. Glasgow
      Coma Scale mostly decreased in the AES group by about 40% in the level <=8. All
      patients in the AES group suffered from status epilepticus and 46.67% of them had
      body temperature >40C. Most of the cases in the AES group had longer duration of
      stay in the hospital. The median serum NSE level in the AES group was 157.86
      ng/mL, and this value was significantly higher than that of the non-AES group
      (10.96 ng/mL; P<0.05). CONCLUSION: AES cases showed higher levels of serum NSE.
      These results indicate that serum NSE is a good indicator of neuronal brain
      injury.

PMID- 29042875
TI  - Current Challenges and Future Opportunities for Child and Adolescent Psychiatry
      in Japan.
AB  - Japan has been facing a serious shortfall of child and adolescent psychiatric
      workforce relative to increasing service needs. Likely because of a combination
      of limited workforce supply and limited trust or perception of effectiveness,
      mental health services are under-utilized by the educational and child welfare
      systems. Child and adolescent psychiatry (CAP) has not been a formally
      established specialty in Japan. The lack of basic structure in the specialty most
      likely contributes to a lack of training facilities, limited exposure to and
      interest in the specialty, and hence an inadequate workforce. To date, there
      exists no standardized training program for CAP in Japan and each training
      hospital determines its own teaching curriculum and training content. Clinical
      experience in CAP varies greatly among hospitals. To solve current problems in
      child and adolescent psychiatry in Japan, we advocate for the development and
      establishment of a more standardized child and adolescent psychiatry training
      system that is akin to what exists in the US and that teaches and evaluates
      according to specific competencies. Through standardizing care and education and
      ultimately improving workforce, the quality of mental health services can be
      raised. The tragic and costly consequences of unidentified and untreated mental
      illness in youth can be avoided by taking timely evidence based actions in
      partnership with others.

PMID- 29042876
TI  - Does Emotional Intelligence Fluctuate within Clinical Depressive Condition?
AB  - OBJECTIVE: Emotional intelligence (EI) is regarded an important factor related to
      psychiatric disorder. Most of previous studies of EI and depression only dealt
      with EI in present of depressive symptoms. Our study investigated EI both before
      and after remission of depression and to identify which component of EI is
      changeable by depression condition. METHODS: EI was evaluated for 23 depression
      patients and 44 normal control participants. Adult Emotional Quotient Test (AEQT)
      was used as subjective EI measure and Emotional Literacy Test (ELT) was used as
      objective EI measure to both groups. RESULTS: During the initial evaluation of
      the subjective EI, patient group reported significantly lower scores than control
      group on all AEQT sub-domains except 'empathy'. However, group difference on
      'utilization' disappeared after the remission evaluation. There was no
      significant difference within the objective EI measure. CONCLUSION: According to
      the result of the study, EI could be sub-divided into trait-dependent EI and
      state-dependent EI. Further implication, strength and limitation were discussed.

PMID- 29042877
TI  - Impaired Social and Role Function in Ultra-High Risk for Psychosis and First
      Episode Schizophrenia: Its Relations with Negative Symptoms.
AB  - OBJECTIVE: Psychosocial dysfunction was a nettlesome problem of schizophrenia
      even in their prodromal phase as well as in their first-episode. In addition, its
      relations with psychopathology were not determined. The aim of the present study
      was to examine whether the social and role function impairment was found in ultra
      high risk for psychosis (UHR) individuals as well as first-episode schizophrenia
      patients and to explore its relations with psychopathology. METHODS: Thirty-seven
      normal controls, 63 UHR participants and 28 young, first-episode schizophrenia
      patients were recruited. Psychosocial functioning was examined by using Global
      function: Social and Role scale. Psychopathologies of positive, negative and
      depressive symptom were also measured. RESULTS: Social and role functioning in
      UHR were compromised at the equivalent level of those of first-episode
      schizophrenia patients. Multiple linear regression analysis revealed that social
      and role dysfunction was associated with negative symptoms in each UHR and first
      episode schizophrenia group. CONCLUSION: These findings suggest that the
      significant impairment of social and role function may be appeared before the
      active psychosis onset at the level of extent to those of first-episode
      schizophrenia patients. The psychosocial intervention strategy especially
      targeting the negative symptoms should be developed and provided to individuals
      from their prepsychotic stage of schizophrenia.

PMID- 29042878
TI  - The Evaluation Acute Traumatic Stress Level in Close Relatives of Stroke
      Patients.
AB  - OBJECTIVE: Stroke is the second most common cause of death and the leading cause
      of adult disability. Both stroke patients and their family can therefore
      experience increased traumatic stress level. METHODS: The participants are close
      relatives of patients (n=65) who had a first time stroke (CRPWS) hospitalized. A
      control group (CG) (n=61), who had no history of chronic illness in their family
      and had at least one traumatic life event experience. The National Institutes of
      Health Stroke Scale, Modified Rankin Scale, Personal Information Form, Life
      Events Checklist, Traumatic Stress Symptom Scale, and Multidimensional Scale of
      Perceived Social Support, were used in the study. RESULTS: We found no
      significant association between NIHSS and MRS of patients and traumatic stress
      level of the family member. The traumatic stress level was significantly higher
      in the CRPWS group than in the CG group. Traumatic stress level was higher in
      women than men and was not associated with perceived social support in the CRPWS
      group. CONCLUSION: The traumatic stress level of the relatives was not associated
      with the clinical features of the stroke patients. In the early phase, after the
      diagnosis of stroke, psychological support may be important to prevent CRPWS from
      PTSD.

PMID- 29042879
TI  - Post-Traumatic Stress Disorder, Depression and Anxiety among North Korean
      Refugees: A Meta-Analysis.
AB  - OBJECTIVE: Post-traumatic stress disorder is common among North Korean refugees
      who have fled their country for economic, financial and humanitarian reasons. Co
      morbid depression and anxiety are also common among North Korean refugees, due to
      the difficulties they have faced within their country and during their escape
      journey. Depression and anxiety complicate treatment for post-traumatic stress
      disorder, and lead to poorer outcomes. Thus, the aim of the present study was to
      provide a meta-analysis of studies investigating post-traumatic stress disorder,
      depression, and anxiety among North Korean refugees. METHODS: Selected articles
      were published in English, and included measures of post-traumatic stress, and/or
      depression and anxiety. 10 studies were included in the depression meta-analysis,
      and 6 in the anxiety meta-analysis. RESULTS: A random-effects model revealed
      strong, significant associations between post-traumatic stress and depression,
      r=0.63, 95% CI (0.51, 0.72), p<0.001, z=8.33, and anxiety, r=0.51, 95% CI (0.36,
      0.63), p<0.001, z=6.07. The relationships between post-traumatic stress,
      depression and anxiety were higher among adults and those with more than five
      years outside of North Korea. CONCLUSION: Depression appears to be an important
      treatment focus for North Korean refugees with post-traumatic stress.

PMID- 29042880
TI  - Initial Psychometric Properties of the Korean Altman Self-Rating Mania Scale:
      Preliminary Validation Study in a Non-Clinical Sample.
AB  - OBJECTIVE: We aimed to examine the reliability and validity of the Korean Altman
      Self-Rating Mania Scale (K-ASRM) in a large sample of Korean non-clinical
      undergraduates. METHODS: Participants (n=1,091) filled out the K-ASRM with other
      self-report questionnaires assessing bipolarity, mood symptoms and affect.
      Reliability test, exploratory factor analysis and correlation analyses were
      conducted to examine its psychometric properties. RESULTS: The reliability of the
      K-ASRM was adequate (Cronbach's alpha=0.73, item-to-total correlation 0.53-0.78)
      and the exploratory factor analysis yielded one factor of mania. The K-ASRM
      demonstrated significant associations with measures of hypomanic personality
      (r=0.33), lifetime history of hypomanic symptoms (r=0.23). Also, the K-ASRM was
      significantly correlated with positive affect (r=0.53), negative affect (r=-0.17)
      and depressive symptoms (r=-0.35). CONCLUSION: These results suggest preliminary
      possibility that the K-ASRM can be utilized as self-rating tool for mania in
      Korea as well as future directions for further validation.

PMID- 29042881
TI  - Clinical Validation of the Psychotic Depression Assessment Scale, Hamilton
      Depression Rating Scale-6, and Brief Psychiatric Rating Scale-5: Results from the
      Clinical Research Center for Depression Study.
AB  - OBJECTIVE: The aim of this study was to validate the psychotic depression
      assessment scale (PDAS), which includes the six-item melancholia subscale from
      the Hamilton depression rating scale (HAMD-6) and the five-item psychosis
      subscale from the brief psychiatric rating scale (BPRS-5). Data from the Clinical
      Research Center for Depression (CRESCEND) study, which is a 52-week naturalistic
      trial, were analyzed. METHODS: Fifty-two patients with psychotic depression from
      the CRESCEND study met our inclusion criteria. The patients underwent the
      following psychometric assessments: the PDAS, including HAMD-6 and BPRS-5, the
      clinical global impression scales, the HAMD, the positive symptom subscale, and
      the negative symptom subscale. Assessments were performed at the baseline and
      then at weeks 1, 2, 4, 8, 12, 24, and 52. Spearman correlation analyses were used
      to assess the clinical validity and responsiveness of the PDAS. RESULTS: The
      clinical validity and responsiveness of the PDAS, including HAMD-6 and BPRS-5,
      were acceptable, with the exception of the clinical responsiveness of the PDAS
      for positive symptoms and the clinical responsiveness of BPRS-5 for negative
      symptoms. CONCLUSION: The clinical relevance of the PDAS has been confirmed and
      this clinical validation will enhance its clinical utility and availability.

PMID- 29042882
TI  - Validation of the Korean Depressive Symptom Inventory-Suicidality Subscale.
AB  - OBJECTIVE: The present study aimed to validate a Korean version of the self
      report Depressive Symptom Inventory-Suicidality Subscale (DSI-SS). METHODS: 553
      South Korean undergraduate students (aged 18-34 years, 74.8% females) completed
      questionnaires. Participants completed Korean versions of the self-report
      Depressive Symptom Inventory-Suicidality Subscale (DSI-SS), Beck Depression
      Inventory-II (BDI-II), Insomnia Severity Index (ISI), Beck Scale for Suicide
      Ideation (BSS), and a measure of suicide-related symptom history. RESULTS:
      Results indicated that the DSI-SS demonstrated excellent internal consistency
      (alpha=0.93) and strong convergent validity with the BDI (r=0.57, p<0.01), ISI
      (r=0.27, p<0.01), and BSS (r=0.70, p<0.01). DSI-SS scores also significantly
      differentiated between those reporting a history of suicide attempts compared to
      non-suicide attempters [t (38.80)=-3.28, p<0.05]. CONCLUSION: Given the brevity
      of this measure, and evidence for its validity, the Korean version of the DSI-SS
      may be particularly promising for clinical and empirical use as a screening tool
      among South Korean undergraduates.

PMID- 29042883
TI  - Feasibility of the Korean version of the Bipolar Depression Rating Scale in
      Adolescents with Early-Onset Bipolar Disorder.
AB  - OBJECTIVE: This study explores the feasibility and psychometric properties of the
      Korean version of the Bipolar Depression Rating Scale (BDRS) in adolescents with
      Early-onset bipolar disorders. METHODS: Fifty-three participants (aged 13-18)
      with early-onset bipolar disorders (40 depressed and 18 euthymic, 5 patients were
      assessed at depressed state and reassessed after remission) were recruited. All
      participants were assessed using the BDRS, the Hamilton Depression Rating Scale
      (HAM-D), the Montgomery-Asperg Depression Rating Scale (MADRS), the Young Mania
      Rating Scale (YMRS), and the Modified Overt Aggression scale (MOAS). RESULTS:
      BDRS exhibited good internal validity and significant correlations with the HAM-D
      and the MADRS. In item to scale correlations, all items on the BDRS were
      significantly correlated with the BDRS total scores except for 'increased motor
      drive' and 'increased speech', 'depressed mood' and 'worthlessness' showed the
      highest mean scores and endorsement rates. BDRS score of the depressed group was
      significantly higher compared with the euthymic group. Three factors (i.e.,
      psychosomatic, mood, and mixed) were identified in the principal component
      analysis and hierarchical cluster analysis of the BDRS. CONCLUSION: In this
      study, we report that the Korean version of BDRS is a feasible and reliable tool
      for the assessment of depression in adolescents with Early-onset bipolar
      disorders.

PMID- 29042884
TI  - Reliability and Validity of the Korean Version of the General-Food Craving
      Questionnaire-Trait for Children.
AB  - OBJECTIVE: The General-Food Craving Questionnaire-Trait (G-FCQ-T) is a validated,
      assessment scale for food craving. The aim of this study was to measure its
      reliability and validity for Korean children. METHODS: A total of 172 children
      (94 boys and 78 girls) were selected to fill out a set of questionnaires,
      including the G-FCQ-T, the Children's version of the Dutch Eating Behavior
      Questionnaire (DEBQ-C), and the Three-Factor Eating Questionnaire (TFEQ) in the
      Korean language. RESULTS: The internal consistency (Cronbach's alpha=0.933) and
      test-retest reliability (r=0.653) were satisfactory. The G-FCQ-T showed a
      significantly positive correlation with the DEBQ-C (r=0.560) and the TFEQ
      (r=0.397). The optimum cutoff score of the G-FCQ-T set by Receiver Operating
      Characteristics analysis was 51, with sensitivity and specificity of 0.833 and
      0.825, respectively, for children. CONCLUSION: The G-FCQ-T showed good
      reliability and validity for assessing food craving for children and could become
      a practial instrument in clinical and research settings.

PMID- 29042885
TI  - More Resilience in Males with Probable Bipolar Depression than Probable Unipolar
      Depression among Korean Conscripts.
AB  - OBJECTIVE: This study investigated whether the resilience of males with probable
      bipolar depression (PBD) can be strengthened and compared it to that of males
      with probable unipolar depression (PUD). METHODS: Prospective data for 198
      participants (PBD: 66, PUD: 66, normal control: 66) were analyzed. The
      participants' resilience, bipolarity and severity of depressive symptoms were
      evaluated at baseline and after 5 weeks. Analysis of variance (ANOVA) and
      repeated measure ANOVA was performed for comparing resilience between three
      groups through a basic military training. RESULTS: The PBD group demonstrated
      more resilience than the PUD group at baseline. Participants with PBD became
      significantly more resilient than participants with PUD after 5 weeks (p<0.01,
      F=6.967, eta2p=0.052). CONCLUSION: The study indicates that interventions that
      strengthen resilience need to be developed for males with PBD and that such
      interventions are more effective for males with PBD than PUD.

PMID- 29042886
TI  - Effects of Group Cognitive-Behavioral Therapy in Young Patients in the Early
      Stage of Psychosis.
AB  - OBJECTIVE: To develop a model of group cognitive-behavioral therapy (CBT) for
      Korean patients with early psychosis. METHODS: The group CBT utilized in the
      present study consisted of metacognitive training, cognitive restructuring, and
      lifestyle managements. The Subjective Well-being Under Neuroleptics (SWN-K),
      Ambiguous Intentions Hostility Questionnaire (AIHQ), Drug Attitude Inventory
      (DAI), Beck Depression Inventory (BDI), Perceived Stress Scale (PSS), and
      Clinical Global Impression (CGI) were administered prior to and after CBT
      sessions. The participants were categorized into two groups according to the
      median duration of untreated psychosis (DUP; 4 months). RESULTS: A total of 34
      patients were included in this analysis. From pre- to post-therapy, there were
      significant increases in the SWN-K and DAI scores and significant decreases in
      the hostility subscale of the AIHQ, PSS, and CGI scores. Significant time * DUP
      interaction effects were observed for the SWN-K, DAI, and BDI scores, such that
      there were significant changes in patients with a short DUP but not in those with
      a long DUP. CONCLUSION: The group CBT program had a positive effect on subjective
      wellbeing, attitude toward treatment, perceived stress, and suspiciousness of
      young Korean patients with early psychosis. These effects were particularly
      significant in patients with a short DUP.

PMID- 29042887
TI  - The Prevalence of Depression among Patients with the Top Ten Most Common Cancers
      in South Korea.
AB  - OBJECTIVE: Among the various psychiatric disorders, depression is a common
      comorbid condition in cancer patients. Due to the distinct and diverse nature of
      cancer, the prevalence of depression may be assumed to be affected by differences
      in primary cancer sites. In this study, we explored the prevalence rates of
      depression among the ten most prevalent cancers in South Korea using a national
      patient sample. METHODS: This was a 1-year cross-sectional study using a national
      patient sample provided by the South Korean National Health Insurance in 2011. We
      selected all patients who had received ICD-10 codes of the 10 most prevalent
      cancers and major depressive disorder. Afterwards, the cancer and depression
      groups were merged and analyzed. RESULTS: The MDD prevalence rate was highest in
      lung cancer (11.0%), followed by non-Hodgkin's lymphoma (9.2%), prostate (9.1%),
      bladder (8.8%), breast (7.8%), cervix (7.8%), colorectal (7.7%), stomach (6.9%),
      liver (6.5%), and thyroid cancer (5.6%). Within all cancer groups, patients with
      a MDD diagnosis were significantly older (p<0.05) than non-MDD patients.
      Colorectal, stomach, and thyroid cancer displayed a higher female proportion in
      the MDD group than the non-MDD group. In the subgroup analysis, the prevalence
      rate differed by age and sex. CONCLUSION: The prevalence of depression varied
      according to cancer types. Patients with lung cancer were the most prone to
      experience depression. Because clinical and psychological factors may influence
      MDD prevalence, these factors will need to be studied more closely in the future.

PMID- 29042888
TI  - Cognitive Stimulation as a Therapeutic Modality for Dementia: A Meta-Analysis.
AB  - OBJECTIVE: Although cognitive stimulation (CS) is one of the most popular non
      pharmacological interventions for people with dementia, its efficacy is still
      debatable. We performed a meta-analysis of randomized controlled trials (RCTs) on
      the efficacy of CS in people with dementia. METHODS: Data sources were identified
      by searching PubMed, MEDLINE, Embase, psychINFO, and Cochrane Reviews Library. A
      total of 7,354 articles were identified, and of these, 30 RCTs were selected
      based on the selection criteria. Of these 30 RCTs, 14 were finally included in
      our meta-analysis [731 participants with dementia; 412 received CS (CS group) and
      319 received usual care (control group)]. RESULTS: We found that the people with
      dementia had a moderate benefit from CS. The mean difference between the CS and
      control groups was 2.21 [95% CI (0.93, 3.49), Z=3.38, p=0.00007] in the
      Alzheimer's Disease Assessment Scale-Cognition and 1.41 [95% CI (0.98, 1.84),
      Z=6.39, p<0.00001] in the Mini-Mental State Examination. CS also improved quality
      of life in people with dementia [95% CI (0.72, 3.38), Z=3.02, p=0.003].
      CONCLUSION: CS is effective for improving cognition and quality of life in people
      with dementia; however, its effects were small to moderate.

PMID- 29042889
TI  - Screening Ability of Subjective Memory Complaints, Informant-Reports for
      Cognitive Decline, and Their Combination in Memory Clinic Setting.
AB  - OBJECTIVE: This study aimed to compare the accuracy of subjective memory
      complaints, informant-reports for cognitive declines, and their combination for
      screening cognitive disorders in memory clinic setting. METHODS: One-hundred
      thirtytwo cognitively normal (CN), 136 mild cognitive impairment (MCI), and 546
      dementia who visited the memory clinic in the Seoul National University Hospital
      underwent standardized clinical evaluation and comprehensive neuropsychological
      assessment. The Subjective Memory Complaints Questionnaire (SMCQ) and the Seoul
      Informant Report Questionnaire for Dementia (SIRQD) were used to assess
      subjective memory complaints and informant-reports for cognitive declines,
      respectively. RESULTS: Both SMCQ and SIRQD showed significant screening ability
      for MCI, dementia, and overall cognitive disorder (CDall: MCI plus dementia)
      (screening accuracy: 60.1-94.6%). The combination of SMCQ and SIRQD (SMCQ+SIRQD)
      was found to have significantly better screening accuracy compared to SMCQ alone
      for any cognitive disorders. SMCQ+SIRQD also significantly improved screening
      accuracy of SIRQD alone for MCI and CDall, but not for dementia. CONCLUSION: Our
      findings suggest that the combined information of both subjective memory
      complaints and informant-reports for cognitive declines can improve MCI screening
      by each individual information, while such combination appears not better than
      informant-reports in regard of dementia screening.

PMID- 29042890
TI  - Effects of Psychotropic Drugs on Seizure Threshold during Electroconvulsive
      Therapy.
AB  - OBJECTIVE: To analyze the relationship between seizure threshold (ST) and
      psychotropic drugs in patients treated with ECT. METHODS: We examined clinical
      data from 43 patients. ST was titrated at each treatment session. We examined
      associations between ST and psychotropic drugs using multivariate correlation
      analyses. Data are presented as initial ST, the difference in ST between the
      first and 10th sessions (DeltaST10th), and the mean difference in ST between the
      first and last sessions (mean DeltaSTlast). RESULTS: Multivariate regression
      analyses showed associations between initial ST and the total chlorpromazine
      equivalent dose of antipsychotics (beta=0.363, p<0.05). The total fluoxetine
      equivalent dose of antidepressants was associated with DeltaST10th (beta=0.486,
      p<0.01) and mean DeltaSTlast (beta=0.472, p<0.01). CONCLUSION: Our study
      elucidated possible effects of psychotropic drugs on ST shifts. Larger doses of
      antipsychotics were associated with higher initial ST, whereas higher doses of
      antidepressants were associated with stronger shifts in ST.

PMID- 29042891
TI  - Differential Effects of Obesity on Obstructive Sleep Apnea Syndrome according to
      Age.
AB  - OBJECTIVE: To evaluate the effect of obesity on obstructive sleep apnea syndrome
      (OSAS) by age in relation to anthropometric measurements. METHODS: The medical
      records of 1,110 participants diagnosed with OSAS were analyzed according to age.
      All participants underwent nocturnal polysomnography and had their body mass
      index, waist circumference, neck circumference (NC), and waist-to-hip ratio
      measured. RESULTS: According to the multiple linear regression analysis model for
      the natural logarithm of the apnea-hypopnea index treating all four
      anthropometric measurements and gender as covariates, the final stepwise model
      accounted for an increasing percentage of the variability in the severity of OSAS
      as a function of age: 7.0, 9.1, 14.5, and 25.6% for those aged <30, 30-39, 40-49,
      and 50-59 yrs, respectively. It accounted for a decreased percentage among those
      60-69 (20.3%) and 70 yrs or older (3.9%). The correlation between NC and the
      severity of OSAS linearly increased as a function of age for those aged 30-59
      yrs, peaked among those in their 60s, and dramatically decreased thereafter.
      CONCLUSION: Middle-aged patients with OSAS were more likely to be obese, as
      measured by anthropometric measurements, than were younger or older OSAS
      patients. In particular, the predictive value of NC was significantly lower for
      younger and older OSAS patients.

PMID- 29042892
TI  - Modest Improvement of Untreated Severe Sleep-Disordered Breathing in the Middle
      Aged and Elderly.
AB  - OBJECTIVE: It has been reported that untreated sleep-disordered breathing (SDB)
      deteriorates over time, however this remains contentious. The aim of the present
      study is to evaluate the clinical course of SDB in middle-aged and older SDB
      patients, and to identify how relevant factors contribute to the change in SDB
      severity. METHODS: Baseline and follow-up polysomnographic data of 56 untreated
      SDB patients (mean age, 61.2+/-5.71) were obtained retrospectively and the mean
      interval was 62.4+/-22.0 months. Subgroup analysis was performed based on the
      baseline severity, and the factors associated with the course of SDB were
      analyzed. RESULTS: At the baseline, 13 subjects were simple snorers, 15 had mild
      to moderate SDB, and 28 were severe SDB patients. While there was no significant
      change in apnea-hypopnea index (AHI) as a whole, subgroup analysis showed
      decrease of AHI in severe SDB patients (43.9+/-10.6 to 35.6+/-20.0, p=0.009). The
      change in supine time percent and baseline AHI were associated with the change in
      AHI (beta=0.387, p=0.003; beta=-0.272, p=0.037). CONCLUSION: Untreated SDB did
      not deteriorate over time with modest improvement in severe SDB. A proportion of
      severe SDB patients might expect decrease in SDB severity irrespective of changes
      in sleep position or body weight.

PMID- 29042893
TI  - Periodic Limb Movements in Sleep is Associated with Increased Mortality.
AB  - OBJECTIVE: To elucidate the association between periodic limb movements in sleep
      (PLMS) and mortality. METHODS: Nocturnal polysomnographic recordings of 1,344
      subjects obtained from 1995 to 2008 were reviewed. The subjects were divided into
      four groups based on PLMS and insomnia: reference group (PLMS<=5), insomnia group
      (PLMS<=5 with insomnia symptoms), 5<PLMS<=15 group, and the PLMS>15 group. We
      searched each subject's Identification Number in the death records from the
      Statistics of Korea, the national bureau of statistics, to determine deaths in
      the cohort that occurred prior to December, 2013. Cox-proportional hazard
      regression and Kaplan-Meier survival curve analyses were used to compare
      mortality among the four groups. RESULTS: Hazard ratios (HRs) in the 5<PLMS<=15
      and PLMS>15 groups were significantly higher than that in the reference group
      before adjusting for age and gender [HR, 3.37; 95% confidence interval (CI), 1.73
      6.55; p<0.001; HR, 5.77; 95% CI, 3.24-10.29; p<0.001]. Only the PLMS>15 group had
      a higher mortality rate than that in the reference group after adjusting for age,
      gender, and sleep efficiency (HR, 1.99; 95% CI, 1.06-2.21; p=0.033). CONCLUSION:
      These results suggest that PLMS may be associated with increased mortality.

PMID- 29042894
TI  - Genetic Association of the PERIOD3 (Per3) Clock Gene with Bipolar Disorder.
AB  - OBJECTIVE: Circadian rhythms have been linked to psychiatric disorders such as
      Depression and Bipolar Disorder (BD). Given previous evidences of sleep/circadian
      disturbances as well as the genetic susceptibility for BD, we decided to
      investigate the possible link between the PERIOD3 (Per3) circadian gene and BD.
      METHODS: This is a genetic association case (BD) vs. control study of the Per3
      gene. We further subdivided our BD sample into "good sleepers" (PSQI <=5) and
      "poor sleepers" (PSQI>5) according to the Pittsburgh Sleep Quality Index (PSQI)
      global score, and then we assessed genetic association of the Per3 gene with
      sleep quality in the BD group. RESULTS: There were 209 cases and 213 controls in
      our sample. The GT genotype of the SNP rs707467 significantly associated with BD
      (chi2=8.80; p-value=0.01; adjusted residual=+/-2.6). We also found significant
      association of the SNP rs10462020 allele T with BD (chi2=5.81; p-value=0.01) as
      well as the genotype TT (chi2= 6.01; p-value=0.04; adjusted residual=+/-2.4).
      CONCLUSION: In this study we demonstrated evidences of genetic association
      between the Per3 gene and BD. The results of association between the Per3 gene
      and BD in our sample may bring additional evidence to the former findings of
      association between the Per3 gene and BD.

PMID- 29042895
TI  - No Association between the Polymorphism rs6943555 in the AUTS2 Gene and
      Personality Traits in Japanese University Students.
AB  - OBJECTIVE: The autism susceptibility candidate 2 (AUTS2) gene has been implicated
      in multiple neurological disorders. Several recent studies have revealed that the
      polymorphism rs6943555 in the AUTS2 gene is broadly associated with human mental
      function and behavior. Therefore, in the present study we investigated whether
      the polymorphism rs6943555 is associated with human personality traits in
      Japanese university students. In addition, our previous study reported that the
      AUTS2 rs6943555-rs9886351 haplotype is associated with alcohol dependence. As a
      preliminary analysis, we also examined whether the AUTS2 haplotypes are related
      to personality traits. METHODS: After written informed consent had been obtained
      from the participants, two AUTS2 polymorphisms were analyzed, and personality was
      assessed using the Temperament and Character Inventory (TCI) in 190 university
      students. In addition, in order to exclude the influence of the results for
      students with mental health problems, we gave the Patient Health Questionnaire-9
      (PHQ-9) to all subjects. RESULTS: In all the subjects, there was a main effect of
      the polymorphism rs6943555 genotype on reward dependence (p=0.038) and
      cooperativeness (p=0.031), although the significance was lost on Bonferroni
      correction. Similarly, on analysis that excluded the subjects with PHQ-9
      scores>=10, no significant association with any TCI dimension score among the
      rs6943555 genotypes was seen. There was no effect of the rs6943555-rs9886351
      haplotypes on the TCI dimension scores. CONCLUSION: This study suggests that the
      polymorphism AUTS2 rs6943555 is not associated with personality traits. Further
      large-scale studies with more subjects using other self-report questionnaires are
      needed.

PMID- 29042896
TI  - Genome-Wide Supported Risk Variants in MIR137, CACNA1C, CSMD1, DRD2, and GRM3
      Contribute to Schizophrenia Susceptibility in Pakistani Population.
AB  - OBJECTIVE: Schizophrenia is a chronic neuropsychiatric disease afflicting around
      1.1% of the population worldwide. Recently, MIR137, CACNA1C, CSMD1, DRD2, and
      GRM3 have been reported as the most robustly emerging candidates involved in the
      etiology of schizophrenia. In this case control study, we performed an
      association analysis of rs1625579 (MIR137), rs1006737, rs4765905 (CACNA1C),
      rs10503253 (CSMD1), rs1076560 (DRD2), rs12704290, rs6465084, and rs148754219
      (GRM3) in Pakistani population. METHODS: Schizophrenia was diagnosed on the basis
      of the Diagnostic and Statistical Manual of Mental Disorders 4th ed (DSM-IV).
      Detailed clinical information, family history of all patients and healthy
      controls were collected. RFLP based case control association study was performed
      in a Pakistani cohort of 508 schizophrenia patients and 300 healthy control
      subjects. Alleles and genotype frequencies were calculated using SPSS. RESULTS: A
      significant difference in the genotype and allele frequencies for rs4765905,
      rs1076560 and rs6465084 were found between the patients and controls (p=0.000).
      CONCLUSION: This study provides substantial evidence supporting the role of
      CACNA1C, GRM3 and DRD2 as schizophrenia susceptibility genes in Pakistani
      population.

PMID- 29042897
TI  - Association between GABA3 Gene Polymorphisms and Attention Deficit Hyperactivity
      Disorder in Korean Children.
AB  - OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is common disorder of
      the school-age population. ADHD is familial and genetic studies estimate
      heritability at 80-90%. The aim of the present study was to investigate the
      association between the genetic type and alleles for gamma-aminobutyric acid
      receptor subunit beta-3 (GABA3) gene in Korean children with ADHD. METHODS: The
      sample consisted of 180 ADHD children and 159 control children. We diagnosed ADHD
      according to DSM-IV. ADHD symptoms were evaluated with Conners' Parent Rating
      Scales and Dupaul Parent ADHD Rating Scales. Blood samples were taken from the
      339 subjects, DNA was extracted from blood lymphocytes, and PCR was performed for
      GABA3 rs2081648, rs1426217 and rs981778 Polymorphism. Alleles and genotype
      frequencies were compared using the chi-square test. We compared the allele and
      genotype frequencies of GABA3 gene polymorphism in the ADHD and control groups.
      RESULTS: This study showed that there was a significant correlation among the
      frequencies of the rs2081648 (OR=0.71, 95% CI=0.51-0.98, p=0.040) of alleles of
      MAO, but the final conclusions are not definite. Follow up studies with larger
      patient or pure subgroups are expected. CONCLUSION: These results suggested that
      GABA3 might be related to ADHD symptoms.

PMID- 29042898
TI  - Prediction of Treatment Response to Donepezil using Automated Hippocampal
      Subfields Volumes Segmentation in Patients with Mild Alzheimer's Disease.
AB  - Previous studies reported some relationships between donepezil treatment and
      hippocampus in Alzheimer's disease (AD). However, due to methodological
      limitations, their close relationships remain unclear. The aim of this study is
      to predict treatment response to donepezil by utilizing the automated
      segmentation of hippocampal subfields volumes (ASHS) in AD. Sixty four AD
      patients were prescribed with donepezil and were followed up for 24 weeks.
      Cognitive function was measured to assess whether there was a response from the
      donepezil treatment. ASHS was implemented on non-responder (NR) and responder
      (TR) groups, and receiver operator characteristic (ROC) analysis was conducted to
      evaluate the sensitivity, specificity, and accuracy of hippocampal subfields in
      predicting response to donepezil. The left total hippocampus and the CA1 area of
      the NR were significantly smaller than those of the TR group. The ROC curve
      analysis showed the left CA1 volumes showed highest area under curve (AUC) of
      0.85 with a sensitivity of 88.0%, a specificity of 74.0% in predicting treatment
      response to donepezil treatment. We expect that hippocampal subfields volume
      measurements that predict treatment responses to current AD drugs will enable
      more evidence-based, individualized prescription of medications that will lead to
      more favorable treatment outcomes.

PMID- 29042899
TI  - Evidence for Hypothalamus-Pituitary-Adrenal Axis and Immune Alterations at
      Prodrome of Psychosis in Males.
AB  - We aimed to investigate the inflammatory substrate in psychosis by evaluating
      both the Hypothalamus-Pituitary-Adrenal axis function and immune state at
      prodrome. This involved the recruitment of Ultra High Risk (UHR) of Psychosis
      subjects, Healthy Controls (HC) and patients with established Schizophrenia
      (CHRON). Serum cortisol at 3 different times throughout the day was measured. The
      Dexamethasone Suppression Test was performed plus 12 circulating cytokines were
      measured. The UHR subjects presented increased IL-4 levels compared with both the
      HC and CHRON patients. In contrast the UHR differed only from the CHRON group
      regarding the endocrine parameters. In conclusion, IL-4 appears to play a key
      role at prodrome.

PMID- 29042900
TI  - Regional Beta Index of Electroencephalography May Differentiate Alzheimer's
      Disease from Depression.
AB  - Differentiating early Alzheimer's disease (AD) from depression with cognitive
      impairment is challenging in the elderly. To develop a model for differentiating
      these two conditions using electroencephalography (EEG), we enrolled 11 patients
      with early probable AD and 11 age- and cognitive function-matched patients with
      major depressive disorder (MDD) and compared the EEG relative powers of 9 scalp
      regions. Compared to the MDD group, the AD group had a higher global theta
      relative power (p=0.021). In the MDD group, beta relative power was higher in the
      mid-central region than in the left or right central regions (p<0.01). The
      prediction model that included global theta relative power and regional beta
      index was able to discriminate AD from MDD (AUC=0.893, p=0.002). A combination of
      global theta relative power and intra-individual regional differences in beta may
      differentiate early AD from MDD with cognitive impairment.

PMID- 29042902
TI  - Unusual Case of Posterior Reversible Encephalopathy Syndrome in a Patient with
      Anti-glomerular Basement Membrane Antibody Glomerulonephritis: A Case Report and
      Review of the Literature.
AB  - Posterior reversible encephalopathy syndrome (PRES) is characterized by a
      clinical and radiological entity with the sudden onset of seizures, headache,
      altered consciousness, and visual disturbances in patients with the findings of
      reversible vasogenic subcortical edema without infarction. Hypertension, renal
      disease, and autoimmune disease are co-morbid conditions of PRES. Nevertheless,
      there have only been a few case reports of PRES in a patient with anti-glomerular
      basement membrane antibody glomerulonephritis (anti-GBM GN). This paper presents
      the possible first Korean case of a 36-year-old woman with the striking features
      of PRES. She presented with a sudden onset of visual blindness, headache, and
      seizure. The brain MRI images revealed hyperintense lesions in both the occipital
      and parietal lobes, which suggested vasogenic edema. Three months before this
      presentation, she was diagnosed with anti-GBM GN. Since then, she underwent
      immunosuppression with cyclophosphamide and steroid, and hemodialysis for renal
      failure with a treatment of anti-GBM GN.

PMID- 29042901
TI  - Vitamin D and Hypertension.
AB  - Vitamin D has the pleiotropic effects in multiple organ systems, and vitamin D
      deficiency was suggested to be associated with high blood pressure according to
      previous reports. Several interventional studies have examined the effect of
      vitamin D supplementation on high blood pressure patients, but the results have
      been inconsistent. In this article, we examined the literature that have proposed
      a mechanism involving vitamin D in the regulation of blood pressure and review
      previous observational and interventional studies that have shown the
      relationship between vitamin D and hypertension among various populations.

PMID- 29042903
TI  - Renal Tubular Acidosis in Patients with Primary Sjogren's Syndrome.
AB  - Primary Sjogren's syndrome (pSS) is characterized by lymphocytic infiltration of
      the exocrine glands resulting in decreased saliva and tear production. It
      uncommonly involves the kidneys in various forms, including tubulointerstitial
      nephritis, renal tubular acidosis, Fanconi syndrome, and rarely
      glomerulonephritis. Its clinical symptoms include muscle weakness, periodic
      paralysis, and bone pain due to metabolic acidosis and electrolyte imbalance.
      Herein, we describe the cases of two women with pSS whose presenting symptoms
      involve the kidneys. They had hypokalemia and normal anion gap metabolic acidosis
      due to distal renal tubular acidosis and positive anti-SS-A and anti-SS-B
      autoantibodies. Since one of them experienced femoral fracture due to
      osteomalacia secondary to renal tubular acidosis, an earlier diagnosis of pSS is
      important in preventing serious complications.

PMID- 29042904
TI  - Central Diabetes Insipidus Linked to Rathke's Cleft Cyst, Polyuria in a 17-year
      old Girl.
AB  - A 17-year-old girl presented with polyuria (7 L/day) and polydipsia for one year.
      Initial urine osmolality was 113mOsm/kg H2O. Following 6 h of fluid restriction,
      serum plasma osmolality reached 300mOsm/kg H2O, whereas urine osmolality was
      108mOsm/kg H2O. Urine osmolality was increased by 427% from 108 to 557mOsm/kg
      after vasopressin challenge. The patient was diagnosed with central diabetes
      insipidus, possibly derived from the atypical occupation of a Rathke's cleft cyst
      at the pituitary stalk following magnetic resonance imaging with enhancement. She
      was discharged with desmopressin nasal spray (10 ug); urine output was maintained
      at 2-3 L/day, and urine osmolality was >300 mOsm/kg. Additional pituitary image
      studies and evaluation of hypopituitarism should be included in the differential
      diagnosis of patients with central diabetes insipidus.

PMID- 29042905
TI  - Photo-elicitation with adolescents in qualitative research: an example of its use
      in exploring family interactions in adolescent psychiatry.
AB  - BACKGROUND: Photo-elicitation is a method used increasingly often in qualitative
      health research, and its positive effect on the research process is well
      established today. Photo-elicitation appears to facilitate verbalization and
      insight and to improve relationships between the researcher and participants,
      thereby enriching the quality of the data collected. Nonetheless, it is barely
      used at all in the field of adolescent psychiatry. With the aim of exploring the
      potential of these methods for research with adolescents receiving psychiatric
      care, we conducted a qualitative photo-elicitation data collection study with
      this population, asking them about family interactions around food. METHODS: The
      data were collected from 15 adolescents and 17 parents during semi-structured
      interviews in which a photo taken by the adolescent served as the focus of
      discussion. Data were explored through inductive thematic analysis. RESULTS:
      Photo-elicitation played a threefold role in this study: (1) it induced the
      teens' interest, thought, and pleasure, (2) it played a mediating function during
      the interviews, and (3) it enabled family interactions to be viewed from the
      adolescent's perspective. Three themes concerning family interactions were found:
      (1) parent-child relationship patterns, (2) the functioning of the family group,
      and (3) the adolescent's individual relation with food, that is, the issue of the
      adolescent's autonomy. CONCLUSIONS: Photo-elicitation proved to be an innovative
      technique in qualitative research in the area of adolescent psychiatry, one that
      enriched the data and enabled the emergence of new themes in this field, related
      in particular to the process by which adolescents develop autonomy.

PMID- 29042906
TI  - Low mood in a sample of 5-12 year-old child psychiatric patients: a cross
      sectional study.
AB  - BACKGROUND: Not much is known about low mood and its associates in child
      psychiatric patients. In this study, we examined the prevalence of low mood, how
      it associates with disruptive behaviour, and affects clinician-rated global
      functioning in child psychiatric outpatients. METHODS: The study population
      consisted of 862 5-12 year-old child psychiatric patients. The study sample was a
      subsample of all 1251 patients attending a child psychiatric outpatient clinic at
      Helsinki University Hospital in 2013-2015 formed by excluding 4 year-old and 13
      year-old patients and those with missing or incomplete data. The parent-rated
      Strengths and Difficulties Questionnaire, collected as part of the routine
      clinical baseline measure, was used as a measure of psychiatric symptoms. The
      diagnoses were set according to ICD-10 by the clinician in charge after an
      initial evaluation period. The Children's Global Assessment Scale (CGAS) score
      set by clinicians provided the measure of the patients' global functioning. All
      information for the study was collected from hospital registers. Associations
      between emotional symptoms and conduct problems/hyperactivity scores were
      examined using ordinal regression in univariate and multivariate models,
      controlling for age and sex. The independent samples T test was used to compare
      the CGAS values of patient groups with low/normal mood. RESULTS: In our sample,
      512 children (59.4%) showed low mood. In multivariate ordinal regression
      analysis, low mood associated with conduct problems (OR 1.93, 95% CI 1.39-2.67),
      but no association was found between low mood and hyperactivity. Low mood was
      prevalent among children with oppositional defiant disorder or conduct disorder
      (51.8%). The global functioning score CGAS was lower among children with parent
      reported low mood (52.21) than among children with normal mood (54.62, p <
      0.001). The same was true in the subgroup of patients with no depression
      diagnosis (54.85 vs. 52.82, p = 0.001). CONCLUSIONS: Low mood is prevalent in
      child psychiatric outpatients regardless of depression diagnosis and it has a
      negative effect on global functioning. Low mood and behavioural problems are
      often associated. It is important to pay attention to low mood in all child
      psychiatric patients. We recommend prevention measures and low-threshold services
      for children with low mood.

PMID- 29042907
TI  - Effects of puerarin combined with conventional therapy on ischemic stroke.
AB  - This study evaluated the use of conventional therapy combined with puerarin on
      ischemic stroke. Eighty patients with ischemic stroke admitted to Tangshan
      Gongren Hospital from March 2014 to September 2015 were randomly divided into two
      groups. The control group was treated with conventional therapy. The observation
      group was treated with an additional puerarin injection of 400 mg/day. The
      patients in both groups were examined for clinical neurological signs and
      symptoms. The levels of biochemical markers as well as changes in hemorheology
      were measured after the intervention and compared among the groups. Our results
      indicate that the language expression was significantly better in the observation
      group after the intervention (p<0.05). Additionally, the aphasia quotient was
      higher (p<0.05), the neurological deficit score was lower (p<0.05), and the
      functional ability score was higher (p<0.05). The plasma S-100B and NSE levels
      were lower (p<0.05), the whole blood viscosity and plasma viscosity were lower
      (p<0.05), and the levels of corticotropin-releasing hormone, corticotropin,
      cortisol, adrenaline and norepinephrine were lower (p<0.05). Our findings led to
      the conclusion that the use of puerarin can effectively improve the language
      function, reduce neurological damage, reduce blood viscosity, reduce stress
      response and improve quality of life.

PMID- 29042908
TI  - Nursing interventions in depressed children with low serum levels of BDNF.
AB  - The purpose of this study was to investigate the correlation between brain
      derived neurotrophic factor (BDNF) in serum and depression in children, and
      explore the effects of different nursing protocols on patients with low levels of
      BDNF. We recruited 128 children with depression and 50 healthy subjects. Compared
      with healthy controls, the mRNA and protein levels of BDNF in serum were lower in
      children with depression (p<0.01). We selected 60 depressed children with low
      BDNF and randomly divided them in two groups: comprehensive nursing (n=30) and
      regular nursing (n=30). Compared to healthy children, there was a significant
      increase in Hamilton depression (HAMD) scores in patients with depression in
      childhood (p<0.01). After treatment, BDNF protein expression was higher in the
      comprehensive nursing group than that in the regular nursing group (p<0.05).
      Also, the HAMD score in the comprehensive nursing group was significantly lower
      than that in the regular nursing group (p<0.05). Compliance to treatment and
      quality of life after treatment improved in the comprehensive nursing group
      compared with the regular nursing group (p<0.05). Overall, a decrease in BDNF
      expression is closely correlated with depression, and comprehensive nursing care
      can significantly ameliorate the depression symptoms in pediatric patients,
      increase the BDNF expression, and improve compliance and quality of life. These
      results provide theoretical and practical significance for clinical nursing care
      of patients with depression in childhood.

PMID- 29042909
TI  - Elevation of PTPN1 promoter methylation is a significant risk factor of type 2
      diabetes in the Chinese population.
AB  - The present study aimed to investigate the contribution of DNA methylation of the
      protein tyrosine phosphatase, non-receptor type 1 (PTPN1) gene to the
      susceptibility to type 2 diabetes (T2D). Peripheral blood mononuclear cells
      (PBMCs) were collected from 97 patients with T2D and 97 age- and gender-matched
      controls. DNA methylation of the PTPN1 gene promoter was evaluated by bisulfite
      pyrosequencing. Independent sample t-tests were used to compare the differences
      in the PTPN1 promoter and other phenotypes between the patients with T2D and the
      controls. The results indicated a significant correlation between PTPN1 promoter
      methylation and the risk of T2D. Additionally, a breakdown analysis by gender
      revealed that PTPN1 methylation was associated with an increased risk of T2D in
      females. Furthermore, low-density lipoprotein (r=-0.183, P=0.046) and total
      cholesterol (r=-0.310, P=0.001) were inversely associated with PTPN1 methylation
      in females. In conclusion, the results indicate that elevated PTPN1 promoter
      methylation is a risk factor for T2D in the female Chinese population.

PMID- 29042910
TI  - Tumoricidal activities of pterostilbene depend upon destabilizing the MTA1-NuRD
      complex and enhancing P53 acetylation in hepatocellular carcinoma.
AB  - The present study aimed to assess the tumoricidal effect of metastasis-associated
      protein 1 (MTA1) induced by pterostilbene (PTER) in hepatocellular carcinoma
      (HCC). The SMMC-7721 hepatoma cell line was treated with PTER. Following
      treatment, the mRNA transcript abundance of MTA1 was measured using quantitative
      polymerase chain reaction. Additionally, cell viability was determined using an
      MTT assay, and protein expression was measured through western blotting. Cell
      invasion, motility and apoptosis, as well as the cell cycle, were also
      investigated. Following PTER treatment, MTA1, histone deacetylase (HDAC) 1 and
      HDAC2 were downregulated, whereas the ratio of acetyl-p53 to total p53 was
      increased in HCC cells. Cell viability decreased as the PTER dose increased. MTA1
      may be associated with proliferation, motility, invasion and metastasis in HCC
      cells. PTER appeared to repress cell proliferation, trigger apoptosis, induce
      cell cycle arrest, and inhibit motility and invasion via MTA1 in human liver
      cancer cells. The results of the present study demonstrated that PTER can
      downregulate the MTA1-nucleosome remodeling and deacetylase complex, and enhance
      p53 acetylation to inhibit the growth of tumor cells in HCC.

PMID- 29042912
TI  - HPV vaccination in boys: Determining the clinical relevance of this strategy.

PMID- 29042911
TI  - Nalbuphine analgesic and anti-inflammatory effects on patients undergoing
      thoracoscopic lobectomy during the perioperative period.
AB  - This study sought to investigate the analgesic effects of nalbuphine on patients
      undergoing thoracoscopic lobectomy during the perioperative period, as well as
      its effects on inflammatory cytokines. We selected 92 patients with early lung
      cancer who were admitted to Xiangyang No. 1 People's Hospital between January
      2016 and December 2016. The patients were randomly divided into control and
      observation groups (n=46 each). All patients underwent thoracoscopic lobectomy,
      with those in the observation group receiving intravenous nalbuphine
      hydrochloride prior to induction (the control group received saline).
      Intraoperative blood loss, operation time and anesthetic dosages were compared
      between groups. The analgesic effects during the perioperative period were
      compared using a visual analogue scale. The adverse effects of anesthetics
      (nausea, vomiting, dizziness and drowsiness) were compared between the two
      groups. Finally, serum inflammatory cytokine [tumor necrosis factor-alpha (TNF
      alpha), interleukin-6 (IL-6) and IL-10] levels were measured using ELISA at 1, 3,
      5 and 7 days after operation. There were no significant differences in
      intraoperative blood loss and operation time between the two groups (p>0.05).
      However, dosages of propofol and remifentanil used were lower in the observation
      group than in the control group (p<0.05), and the effective rate of postoperative
      analgesia in the observation group was significantly higher than that in the
      control group (p<0.05). The degree of postoperative pain in both groups were
      lower than preoperative rates (p<0.05), while the incidence of adverse reactions
      in the observation group was significantly lower than in the control group
      (p<0.05). Finally, TNF-alpha, IL-6 and IL-10 levels were significantly lower in
      the observation group relative to the control group at 1, 3, 5 and 7 days after
      operation (p<0.05). Therefore, nalbuphine has a significant analgesic effect
      during thoracoscopic lobectomy. The application of nalbuphine can reduce the
      incidence of adverse reactions, reduce postoperative inflammatory responses, and
      promote rapid patient recovery, thus demonstrating the clinical value of
      nalbuphine.

PMID- 29042913
TI  - Paediatric Virology as a new educational initiative: An interview with Nobelist
      Professor of Virology Harald zur Hausen.
AB  - Born in Gelsenkirchen-Buer in Germany on March 11th, 1936, Professor Harald zur
      Hausen, Emeritus Professor of Virology at the University of Freiburg and 2008
      Nobel Prize Laureate in Physiology or Medicine for his discovery of human
      papillomavirus (HPV), which causes cervical cancer, believes that good knowledge
      of virological methods and diagnostic possibilities are an asset for all young
      paediatricians. Professor zur Hausen considers that the creation of an
      educational platform on Paediatric Virology is definitely very beneficial for
      young paediatricians, as this will greatly enhance their knowledge in the field
      of Virology. He very actively advocates the vaccination of boys for the
      eradication of HPV infection and emphasises that male HPV vaccination should be
      included into the current vaccination programmes. He would have certainly
      considered Dr George N. Papanicolaou (Kyme, Island of Euboea, Greece, 1883 -
      Miami, Florida, USA, 1962) as an excellent candidate for the Nobel Prize, stating
      that the contribution of Dr Papanicolaou did not find sufficient recognition in
      the past. In the context of the 3rd Workshop on Paediatric Virology, which will
      be held in Athens, Greece, on October 7th, 2017, Professor zur Hausen will give
      his plenary lecture on 'Paediatric Virology and Oncology: Virus persistence and
      the important first years of life'.

PMID- 29042914
TI  - The educational challenge of Paediatric Virology: An interview with Professor of
      Neonatology Anne Greenough.
AB  - According to Professor Anne Greenough, Professor of Neonatology and Clinical
      Respiratory Physiology at the King's College London (London, UK), Paediatric
      Virology is indeed a rapidly increasing educational challenge. Professor
      Greenough, who in 1992 wrote her book on congenital, perinatal and neonatal
      infections, believes that during the past 3 decades, paediatric health
      professionals are becoming increasingly involved in specialised care and follow
      up of paediatric patients with viral diseases, who require advanced medical care
      and innovative technological services. Moreover, she highlights the expected role
      of new vaccines and antiviral agents that are currently under investigation, as
      well as the impact of emerging viral diseases that require novel prevention
      strategies and therapeutic protocols. However, she notes that the number of
      Paediatric Virologists in any one country is likely to be small; hence, a
      separate paediatric subspecialty needs to be considered carefully. In the context
      of the 3rd Workshop on Paediatric Virology, which will be held in Athens, Greece,
      on October 7th, 2017, Professor Greenough will give her plenary lecture on the
      impact of viral infections on the long term outcomes of prematurely born infants.

PMID- 29042915
TI  - The innovation of the subspecialty of Paediatric Virology: An interview with
      Research Professor of Molecular Virology Anna Kramvis.
AB  - Professor Anna Kramvis, Research Professor of Molecular Virology at the
      University of the Witwatersrand in Johannesburg, South Africa, talks about direct
      acting antiviral treatments against hepatitis C virus (HCV), as well as the
      perspective of the development of an effective vaccine against HCV. She
      emphasises the necessity of vaccination against hepatitis B virus (HBV),
      highlighting that it is very important that vaccination should be administered at
      birth in order to prevent mother-to-child transmission (MTCT) of HBV. Professor
      Kramvis states that vaccination against HBV is safe and that HBV and HCV
      infections are not contraindications for breastfeeding. Regarding the challenge
      of Paediatric Virology, she believes that it is a field that during the last
      years is increasing exponentially, while she concurs that Paediatric Virology
      subspecialty will be a popular choice for infectious diseases subspecialists. In
      the context of the 3rd Workshop on Paediatric Virology, which will be held in
      Athens on October 7th, 2017, Professor Kramvis will give her key lecture on MTCT
      of HBV and HCV.

PMID- 29042916
TI  - The proposal of Paediatric Virology and its perspectives: An interview with
      Professor of Paediatrics Maria Theodoridou.
AB  - Professor Maria Theodoridou, Emeritus Professor of Paediatrics at the University
      of Athens, is one of the few paediatricians in Greece, who have experienced
      almost all the infectious diseases of the second half of the 20th century and
      their severe consequences, prior to the widespread adoption of immunisations. A
      milestone during her career was the establishment of a specialised National
      Reference Unit for the care of paediatric patients with acquired immune
      deficiency syndrome (AIDS) at the 'Aghia Sophia' Children's Hospital in Athens,
      Greece. According to Professor Theodoridou, training on the prevention,
      management and treatment of neonatal and paediatric viral infections represents a
      new educational challenge for both community as well as hospital-based paediatric
      health professionals. The debate of the potential strategically principal role of
      Paediatric Virology subspecialists in the primary, secondary and tertiary
      clinical practice is definitely necessary and needs further discussion and
      evaluation, she adds. She describes the difficulties that Greece, a country under
      a long-standing financial crisis, faces for the hospital-based management of
      paediatric viral infections and refers to the future advances, which are expected
      in the field of diagnosis and treatment of viral infections in neonates and
      children. In the context of the 3rd Workshop on Paediatric Virology, which will
      be held in Athens on October 7th, 2017, Professor Theodoridou will focus on the
      immigration crisis and vaccination policy.

PMID- 29042917
TI  - Viral infections, neonatal mortality and the mystery of the Athenian Agora: An
      interview with Professor of Anthropology Maria Liston.
AB  - Although excavated almost 80 years ago, the infants' 'bone well' of the Athenian
      Agora in Athens, Greece and its contents were never thoroughly evaluated and
      published, until only recently, when a re-analysis of the whole excavation
      findings was performed. The well dates back to the third quarter of the 2nd
      century BC and contained at least 449 infants. The project, which explored the
      causes of neonatal mortality, found that one-third of infants' deaths were
      attributed to neonatal meningitis, based on the presence of bone disposition on
      the endocranial surface of the studied skulls. Despite the non-specific
      differential diagnostic approach of this pathophysiological finding in neonates,
      the determination of the causes of neonatal mortality in the Athenian Agora is
      really an impressive scientific attempt and can be a valuable lesson to all
      neonatal and peadiatric health professionals. According to Professor Maria
      Liston, Associate Professor of Anthropology at the University of Waterloo in
      Canada, who was the principal investigator of the skeletons from the infants'
      'bone well' of the Athenian Agora, neonatal meningitis was the most frequently
      detected cause of neonatal mortality. Viral diseases unquestionably contributed
      to neonatal mortality, she adds and highlights that further research is required
      in collaboration with physicians for the better understanding and interpretation
      of various archaeological findings related to neonatal mortality. In the context
      of the 3rd Workshop on Paediatric Virology, which will be held in October 7th,
      2017 in Athens, Greece, Professor Liston will reveal the role of neonatal and
      paediatric viral infections in the Hellenic antiquity.

PMID- 29042918
TI  - George N. Papanicolaou (1883-1962), an exceptional human, scientist and academic
      teacher: An interview with Dr Neda Voutsa-Perdiki.
AB  - Dr Neda Voutsa-Perdiki, former Director of Exfoliative Cytology at the University
      of Florida (Florida, USA), talks about her academic teacher Dr George N.
      Papanicomicronlaou, referred to as the 'Father of Exfoliative Cytology', and his
      wife Mache, known as Mary Papanicolaou. According to Dr Voutsa-Perdiki, Dr
      Papanicolaou was an exceptional teacher and a unique humanitarian in modern
      medical history. The secret of his scientific success was hard work, dedication,
      love of research, faith and the courage he gained from his wife and colleagues.
      According to Dr Voutsa-Perdiki, although Dr Papanicolaou was nominated for the
      Nobel Prize for at least 5 times, the reason for not receiving it remains
      unclear. His research was mainly clinical and not purely experimental, she adds.
      The official launch of her recently published book about Dr Papanicolaou entitled
      'Dr George and Mache-Mary Papanicolaou - As I knew them' was held on March 1st,
      2017 at the 'Benaki' Museum in Athens, Greece.

PMID- 29042919
TI  - The combined strategy of mesenchymal stem cells and tissue-engineered scaffolds
      for spinal cord injury regeneration.
AB  - Spinal cord injury (SCI) is a traumatic lesion that can result in the loss of
      motor or sensory neurons. Stem cell (SC)-based therapies have been demonstrated
      to promote neuronal regeneration following SCI, by releasing a range of trophic
      factors that support endogenous repair or by differentiating into neurons, or
      glial cells in order to replace the damaged cells. However, numerous limitations
      remain for therapies based on SC transplantion alone, including a low rate of
      survival/engraftment. Nevertheless, scaffolds are 3-dimentional substrates that
      have revealed to support cell survival, proliferation and differentiation in
      vivo, by mimicking a more favorable endogenous microenvironment. A
      multidisciplinary approach, which combines engineered scaffolds with SCs has been
      proposed as a promising strategy for encouraging spinal cord regeneration. The
      present review has focused on the regenerative potential of mesenchymal SCs
      isolated from different sources and combined with various scaffold types, in
      preclinical and clinical SCI studies.

PMID- 29042920
TI  - Screening of differentially expressed proteins in psoriasis vulgaris by two
      dimensional gel electrophoresis and mass spectrometry.
AB  - The aim of the present study was to elucidate differentially expressed proteins
      in lesional tissues of psoriasis vulgaris (PV) and normal tissues. Lesional skin
      tissues were collected from PV patients, along with normal skin tissues from
      healthy individuals. The protein content of the samples was extracted and then
      separated by two-dimensional gel electrophoresis (2-DGE). Any proteins that were
      differentially expressed in the lesional skin of PV patients compared with the
      healthy controls were analyzed by mass spectrometry and bioinformatics. In the
      stratum corneum and dermis of PV patients, the total number of proteins
      identified by 2-DGE was 1,969+/-21 and 1,928+/-49, respectively. Of these, 30
      proteins were differentially expressed in the PV patients, of which 14 were
      identified as: Type 1 keratin cytoskeleton proteins (including K1C10, K1C14,
      K1C15 and K1C16); the type 2 keratin cytoskeleton protein, K2C1; actin-associated
      proteins (including ARP3, ACTA and ACTBM); prohibitin; heat shock proteins (HSPB1
      and CH60); centrosome protein, CP135; and membrane associated proteins (including
      ANXA4 and ANXA5). The differential expression of protein between PV lesions and
      normal tissue can be considered as pathological biomarker. Elucidating the
      abnormal regulation of these proteins can provide mechanism of the development of
      PV and may contribute to significant approaches for PV treatments.

PMID- 29042921
TI  - Protective effects of ellagic acid against tetrachloride-induced cirrhosis in
      mice through the inhibition of reactive oxygen species formation and
      angiogenesis.
AB  - Ellagic acid has been proven to have anticancer, antimutation, antimicrobial and
      antiviral functions. The present study investigated whether treatment with
      ellagic acid was able to prevent tetrachloride (CCl4)-induced cirrhosis through
      the inhibition of reactive oxygen species (ROS) formation and angiogenesis. CCl4
      diluted in olive oil at a final concentration of 10% was used to induce a
      cirrhosis model. A total of 40 mice were random allocated into four groups, as
      follows: Control, cirrhosis model, 7.5 mg/kg ellagic acid and 15 mg/kg ellagic
      acid groups. In the control group, mice were given normal saline. The results
      indicated that ellagic acid exerted a protective effect, evidently preventing
      CCl4-induced cirrhosis. In addition, treatment with ellagic acid significantly
      inhibited collagen I and inducible nitric oxide synthase protein expression
      levels in CCl4-induced cirrhosis mice. Oxidative stress and ROS formation were
      also significantly reduced by ellagic acid treatment. The protein expression
      levels of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2),
      and the caspase-3 activity were significantly inhibited by treatment with ellagic
      acid. In conclusions, these results suggest that ellagic acid exerted protective
      effects against CCl4-induced cirrhosis through the inhibition of ROS formation
      and angiogenesis.

PMID- 29042922
TI  - Endoscopy in the treatment of slit ventricle syndrome.
AB  - The present study aimed to investigate the efficacy of endoscopy in the treatment
      of post-shunt placement for slit ventricle syndrome (SVS). Endoscopic surgery was
      performed on 18 patients with SVS between October 2004 and December 2012. Sex,
      age, causes of the hydrocephalus, ventricular size and imaging data were
      collected and analyzed. All patients were divided into two groups according to
      ventricular size and underwent endoscopic surgeries, including endoscopic third
      ventriculostomy (ETV), endoscopic aqueductoplasty and cystocisternostomy. All
      treated patients were observed postoperatively for a period of 2 to 3 weeks, and
      outpatient follow-up was subsequently scheduled for >12 months. Clinical results,
      including catheter adherence, shunt removal and complications, were analyzed
      during the follow-up period. The success rate of endoscopic surgery was indicated
      to be 82.7%. Syndromes caused by aqueductal stenosis in 15 patients who underwent
      ETV were relieved; however, syndromes in the 3 patients with cerebral
      cysticercosis, suprasellar arachnoid cysts, pinea larea glioma and communicating
      hydrocephalus, respectively, were not relieved and underwent shunt placement
      again. Brain parenchyma, choroid plexus and ependymal tissue were the predominant
      causes for catheter obstruction and the obstruction rate was indicated to be
      77.8% (14/18). Complications, such as pseudobulbar paralysis, infection and
      intraventricular hemorrhage arose in 3 patients. The present study indicates that
      endoscopic treatments are effective and ETV may be considered as a recommended
      option in the treatment of post-shunt placement SVS in hydrocephalus patients.

PMID- 29042923
TI  - ERbeta compensates for the absence of ERalpha function to promote osteoblast
      viability by inhibition of SOST signaling.
AB  - Estrogen receptors alpha and beta (ERalpha and ERbeta) serve key functions in
      bone development and maintenance, and in the metabolism of bone mineral. ERbeta
      and ERalpha form heterodimers, and ERbeta negatively regulates the
      transactivation of ERalpha. ERbeta also inhibits recruitment of ERalpha to the
      estrogen-responsive promoters. However, the relationship of ERalpha and ERbeta in
      the regulation of osteoblast viability and differentiation remains unclear. The
      present study aimed to investigate whether ERbeta plays a role in balancing
      ERalpha activity in osteoblast cells. Downregulation of ERalpha by short hairpin
      RNA (shRNA) was found to significantly increase cell cycle arrest at G1 phase
      (P<0.01). In addition, this effect was found to be significantly enhanced by
      downregulation of ERbeta (P<0.05). Inversely, ERalpha-knocked down osteoblasts
      were treated with ERbeta agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) to
      activate ERbeta. It was found that activation of ERbeta significantly rescued the
      arrest of cell cycle induced by the downregulation of ERalpha (P<0.05).
      Furthermore, downregulation of ERalpha was found to significantly inhibit cell
      viability (P<0.01), and knockdown of ERbeta was found to have a significant
      synergic effect with ERalpha downregulation on the inhibition of cell viability
      (P<0.01). Treatment with ERbeta agonist DPN significantly rescued the effects of
      downregulation of ERalpha on cell viability (P<0.01). It was also demonstrated
      that the synergic effects of ERalpha and ERbeta deletion was via upregulation of
      SOST gene expression, and the subsequent inhibition of OPG and Runx2 gene
      expression. Thus, ERbeta may serve a function in balancing osteoblast viability
      and differentiation induced by ERalpha.

PMID- 29042924
TI  - Inhibition of periderm removal in all-trans retinoic acid-induced cleft palate in
      mice.
AB  - Cleft palate is a common craniofacial birth defect. The aim of the present study
      was to investigate the effect of excess all-trans retinoic acid (atRA) on
      periderm removal and the disappearance of basal medial edge epithelial (MEE)
      cells during palatogenesis, particularly during the stage prior to contact. atRA
      (200 mg/kg) was administered to C57BL/6N mice at embryonic day (E) 12.0 by
      gavage. Fetal palates were processed and analyzed by histology and electron
      microscopy. Single palate shelf peridermal cells were removed and cultured in the
      presence of atRA (3 uM) only or in the presence of or the caspase inhibitor, Z
      VAD (100 uM) only, for 48 h. Once cultured, morphological changes were analyzed
      by histological staining and electron microscopy. A TUNEL assay was used to
      detect apoptotic neurons. Paired palatal shelves with periderm removal were
      cultured in the presence of atRA (3 uM) only or in the presence of Z-VAD (100 uM)
      only for 48 h and analyzed by hematoxylin and eosin staining. At E14.5, medial
      edge epithelium periderm was retained in the atRA-treated palates but had been
      shed prior to contact in the control groups. In addition, atRA was revealed to
      disrupt the cell cycle in the periderm by downregulating p21. Furthermore, atRA
      inhibited apoptosis in the periderm and basal MEE cells; however, atRA exhibited
      no effect on basement membrane degradation in single palatal organ culture.
      Additionally, once paired palates were cultured for 48 h, all of the groups in
      which the periderm had been removed exhibited confluence of the embryonic palatal
      mesenchyme. The present results suggest that periderm removal is inhibited in
      atRA-induced cleft palate in mice and that removal of the periderm contributes to
      EPM confluence in vitro.

PMID- 29042925
TI  - Calreticulin is an effective immunologic adjuvant to tumor-associated antigens.
AB  - As a key molecule involved in cell recognition, calreticulin (CRT) may be
      expressed on the surface of (pre-) apoptotic cells and provide the signal that is
      recognized by dendritic cells (DCs) or other antigen presenting cells (APCs),
      which results in phagocytosis. Within the APCs, tumor-associated antigens (TAAs)
      may be subsequently presented to T lymphocytes, which triggers a specific
      antitumor immune response. It has been hypothesized that CRT is able to act as
      the immunologic adjuvant and translocate itself and TAAs to the cell surface and
      induce a specific antitumor immune response. In the present study, CRT was
      demonstrated to translocate itself and mucin 1 (MUC1), a breast cancer antigen,
      to the surface of 4T1 cells and the MUC1-CRT-coated cells were able to induce
      apoptosis in a time-dependent manner. When DCs were infected with adenovirus
      containing MUC1-CRT, an increase in T cell proliferation and cytokine production
      was exhibited. These results suggest that CRT may act as an immunologic adjuvant
      with MUC1 and induce a strong immune response.

PMID- 29042926
TI  - Anti-EGFR antibody conjugated silica nanoparticles as probes for lung cancer
      detection.
AB  - A well-designed nanosystem [anti-epidermal growth factor receptor-MB-encapsulated
      thiol-terminated silica nanoparticles (EGFR/MB-SHSi) complexes] containing silica
      nanoparticles and near-infrared fluorescence dye (NIRF) methylene blue (MB) was
      established as a tumor-targeted probe for potential lung cancer detection. The
      anti-EGFR/MB-SHSi complexes exhibited desirable and homogenous particle size,
      high bovine serum albumin stability, low hemolytic activity, neutral surface
      charges and negligible cytotoxicity in vitro. Furthermore, the results of
      confocal laser scanning microscopy and flow cytometry confirmed that the EGFR
      targeted function induced high and specific cellular uptake of anti-EGFR/MB-SHSi
      complexes. In vivo investigation of nude mice bearing A549 tumor xenografts
      revealed that anti-EGFR/MB-SHSi complexes possessed strong tumor target ability.
      These observations indicated that anti-EGFR/MB-SHSi complexes may be a safe and
      tumor-targeting probe for the detection of cancer.

PMID- 29042927
TI  - Novel type of peritoneocentesis trocar-assisted distal ventriculoperitoneal shunt
      placement with supervision via a one-port laparoscope.
AB  - Ventriculoperitoneal shunts (VPS) are the primary treatment for hydrocephalus and
      are associated with a high risk of complications, specifically in patients who
      are obese or have abdominal adhesions or shunt revisions. The present study
      describes the use of a novel type of peritoneal catheter peritoneocentesis trocar
      insertion with the assistance of a one-port laparoscope. A total of 36 patients
      with hydrocephalus underwent this novel type of peritoneocentesis trocar-assisted
      VPS. The distal shunt catheter was placed into the right subdiaphragmatic space
      and the catheter was traversed through a single hole drilled through the liver
      falciform ligament. The duration of the laparoscopic surgery ranged from 6-18 min
      (mean 10.4+/-1.6 min). No shunt-related infections or catheter malfunctions or
      injuries to the intra-abdominal organs occurred. The total abdominal incision
      length was 1.0 cm (0.5+0.5 cm). No laparoscopy-related complications were
      observed during follow-up assessments. The novel approach used in the current
      study is very easy to perform, and this method may significantly reduce the risk
      of malfunction complications. The presented method also has the advantages of
      reduced trauma and a simpler surgery. The current study indicated that this
      simple, minimally invasive procedure was beneficial for patients with
      hydrocephalus, specifically in cases of patients with obesity, peritoneal
      adhesions or shunt revisions.

PMID- 29042928
TI  - Long non-coding RNA AB209630 suppresses cell proliferation and metastasis in
      human hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and
      the second most common cause of cancer-related mortalities. With a high potential
      for metastasis and recurrence, HCC is refractory to cure. The present study aimed
      to explore the role of a recent-discovered LncRNA, AB209630, in human HCC, in
      order to provide new insights useful for clinical HCC diagnosis and treatment.
      Reverse transcription-quantitative polymerase chain reaction was performed to
      examine the expression of AB209630 in clinical HCC samples and the adjacent non
      cancerous tissues. The reduced expression of AB209630 observed in HCC tissues and
      cultured HCC cells compared with normal hepatic tissues and cells prompted the
      construction of an AB209630-expressing plasmid with a CBP tag on the plasmid
      backbone. Cell proliferation and colony formation assays were conducted to detect
      the effects of AB209630 on HCC cell proliferation. In addition, Transwell assay
      and wound-healing assays were performed, the results of which further indicated
      that the overexpression of AB209630 inhibited the migration and invasion of HCC
      cells. These results revealed the inhibitory effects of AB209630 on HCC
      progression, and suggest the potential of AB209630 as an inhibitor of HCC for
      clinical use.

PMID- 29042930
TI  - Relevance of clinical features in the prognosis of bronchopulmonary dysplasia in
      premature infants.
AB  - The aim of this study is to determine the accuracy rate of bronchopulmonary
      dysplasia (BPD) diagnosis and risk factors of short-term poor prognosis for
      premature infants. This study analyzed the clinical data of 81 premature infants
      (<32 weeks gestational age) with BPD, who were on oxygen therapy >28 days, and
      survived >36 weeks (corrected age). Outcome measures included treatments,
      conditions on the 28th day after birth, oxygen therapy conditions at the 36th
      week, occurrence of any serious complications during hospital stay. The major
      risk factors affecting prognosis were ventilation duration, duration of oxygen
      therapy, application of steroids, hypothyroidism and severity of BPD (all
      P<0.05). Interventions for complications (n=53) resulted in ceased inhalation of
      oxygen in 12 infants, improvement of symptoms in 26 infants, and were ineffective
      in 15 infants. BPD prognosis can be improved by shortening the duration of
      invasive ventilation and correcting thyroid function.

PMID- 29042929
TI  - Quantitative assessment of salvaged myocardial zone and intramyocardial
      hemorrhage using non-contrast faster T2 mapping in a rat model by 7T MRI.
AB  - The aim of this study was to determine the myocardial area at risk (AAR),
      infarction-core size (IS) and the salvaged myocardial zone (SMZ), and to evaluate
      the imaging and histological characteristics of intramyocardial hemorrhage (IMH)
      after myocardial infarction using non-contrast T2 mapping on 7T magnetic
      resonance imaging (MRI). Twenty Sprague Dawley (SD) rats were randomly divided
      into the sham and model groups (n=10 in each). In the model group, myocardial
      infarction models were established by left anterior descending branch ligation.
      After 24 h, all animals were imaged on a 7.0 Tesla system with cine spiral
      imaging, T2 mapping with late gadolinium enhancement (LGE). The rats were then
      sacrificed for measurement of the IS and AAR using 2,3,5-triphenylterazolium
      chloride (TTC) and hematoxylin and eosin (H&E) staining. T2 mapping revealed that
      the AAR in the model group was significantly higher than that in the sham group.
      No remarkable T2 value was noted in the entire heart of the sham group. LGE and
      TTC staining demonstrated similar IS. T2 mapping and H&E staining revealed a
      similar AAR as well. T2 mapping characterized the IMH as a phenomenon resulting
      from the area of hypointensity in the hyperintensity involving the infarct-core
      zone and corresponding T2 value 928.6+/-1.52 msec with IMH vs. 35.8+/-2.61 msec
      without IMH; n=3 with 18 slices; P=0.032). In conclusion, non-contrast T2 mapping
      was a reliable approach to quantitatively evaluate the SMZ and IMH.

PMID- 29042931
TI  - Delivery of biotinylated IGF-1 with biotinylated self-assembling peptides
      combined with bone marrow stem cell transplantation promotes cell therapy for
      myocardial infarction.
AB  - Cell therapy is a promising approach for cardiac repair. The aim of the present
      study was to determine the feasibility of using biotinylated insulin-like growth
      factor 1 (IGF-1) with biotinylated self-assembling peptides (tethered IGF-1)
      combined with bone marrow stem cells (BMSCs) transplantation for the treatment of
      heart failure. Tethered IGF-1 was synthesized and its effect on H9c2 cells was
      analyzed. Reverse transcription-quantitative polymerase chain reaction and
      western blot assays demonstrated that tethered IGF-1 did not significantly affect
      the expression and phosphorylation of AKT, whereas it significantly increased the
      expression of cardiac troponin T (P<0.01). A rabbit myocardial infarction model
      was constructed and rabbits were divided into four groups: Control group (no
      treatment), group 1 (G1; BMSC transplantation), group 2 (G2; BMSCs + non
      biotinylated IGF-1) and group 3 (G3; BMSCs + tethered IGF-1). At 4 weeks after
      modeling, cardiac tissues were obtained for analysis. In the control group,
      myocardial fibers were disordered, a large number of inflammatory cells
      infiltrated the cardiac tissues, and apoptosis occurred in ~50% of cells.
      However, in G1, G2 and G3, muscle cells were well ordered, and a lesser degree of
      myocardial degeneration and inflammatory cell infiltration was observed. Compared
      with the control group, the apoptosis rates of myocardial cells in G1-G3 were
      significantly decreased (P<0.01). Furthermore, compared with G1 and G2, tissue
      morphology was improved in G3and the number of apoptotic myocardial cells was
      significantly decreased (P<0.01). These results suggest that treatment with
      tethered IGF-1 + BMSCs significantly suppresses cell apoptosis and induces the
      expression of cardiac maturation proteins. These findings provide a novel insight
      into how the delivery of tethered IGF-1 with BMSCs could potentially enhance the
      prognosis of patients with heart failure treatment.

PMID- 29042932
TI  - Cardioprotective effect of Notch signaling on the development of myocardial
      infarction complicated by diabetes mellitus.
AB  - The present study aimed to elucidate the role of Notch signaling in the
      development of myocardial infarction (MI) concomitant with diabetes in vivo and
      in vitro and evaluated the therapeutic effect of the Notch signaling in vitro.
      Streptozotocin-induced diabetic rats were subjected to 25 min of ischemia and 2 h
      of reperfusion. Cardiac troponin T (cTnT) and creatine kinase-MB (CK-MB)
      isoenzyme levels were detected. Infarct size was measured by 2,3,5
      triphenyltetrazolium chloride staining. Myocardial apoptosis and fibrosis were
      examined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling
      and Masson Trichrome staining, respectively. The mRNA and protein levels of Notch
      signaling components, including Notch1, Notch4, Delta-like 1, Jagged1, Mastermind
      like protein 1 and p300, were quantified by reverse transcription-quantitative
      polymerase chain reaction and western blotting analyses, respectively. H9c2 cells
      were treated with/without 33 mM high glucose (HG) and/or subjected to hypoxia in
      the presence/absence of Jagged1. Cell viability and apoptosis were determined by
      MTT assay and Annexin V-fluorescein isothiocyanate/propidium iodide assay. Levels
      of the Notch signaling pathway members were examined. The present findings
      revealed that diabetes elevated CK-MB and cTnT, increased infarct size, induced
      myocardial apoptosis and inhibited the Notch signaling pathway in vivo after
      ischemia/reperfusion. Ischemia/reperfusion augmented the severity of MI in
      diabetic rats. Furthermore, HG reduced cell viability and induced cell apoptosis
      in H9c2 cells after hypoxia exposure, which was inhibited by Jagged1. We also
      found that HG inhibited Notch signaling in H9c2 cells after hypoxia, whereas
      Jagged1 exerted its cardioprotective effect on hypoxic injury (in HG environments
      or not) by activating the Notch signaling pathway. In conclusion, these findings
      suggest that diabetes promoted the progression of MI in vivo and in vitro via the
      inhibition of the Notch signaling pathway. Jagged1 may protect against MI in in
      vitro models by activating Notch signaling.

PMID- 29042933
TI  - Effects of exogenous growth hormone administration on dexamethasone-induced
      growth impairment in adolescent male rats.
AB  - Growth impairment (GI) is one of the adverse effects of dexamethasone (DXM), and
      growth hormone (GH) has been used clinically to improve GI. The present study
      aimed to evaluate the manner in which DXM disturbs the growth rate of
      longitudinal bones, and the recovery effects of GH on DXM-induced GI in the
      longitudinal bones of adolescent male rats. In the first experiment, DXM (0, 0.5,
      1, 2 and 5 mg/kg) was administered subcutaneously to identify a potential dose
      dependent activity and calculate the median effective dose (ED50) of DXM-induced
      GI. The ED50 was identified to be 1.15 mg/kg. In the second experiment, GH (0,
      2.5, 5 and 10 mg/kg) with 1.15 mg/kg DXM was injected subcutaneously to assess
      the recovery effects of GH on DXM-induced GI. The growth rates of the
      longitudinal bones, total height of the growth plate, local mRNA expressions of
      insulin-like growth factor 1 (IGF-1), GH receptor (GHR) and IGF-1 receptor (IGF
      1R), and local protein expression of IGF-1 were measured to evaluate the recovery
      effects of GH on DXM-induced GI. The local expressions of IGF-1, GHR and IGF-1R
      mRNA, and IGF-1 protein were measured using quantitative polymerase chain
      reaction following laser microdissection and antigen-specific
      immunohistochemistry, respectively. GH administration partially recovered DXM
      induced GI in the longitudinal bones and growth plate. GH significantly increased
      the levels of IGF-1, GHR and IGF-1R mRNA in the proliferative zone of the control
      group (P<0.05), whereas it failed to increase them in the proliferative zone of
      the DXM-treated group. Furthermore, GH increased the levels of IGF-1, GHR and IGF
      1R mRNA in the hypertrophic zone of both the vehicle and DXM-treated groups
      (P<0.05). Immunohistochemical analysis of IGF-1 protein expression revealed a
      similar pattern to that of IGF-1 mRNA. These results suggest that increased GH
      insensitivity in the proliferative zone of the growth plate, induced by DXM,
      leads to GI in longitudinal bones. Thus, combined administration of GH with GH
      insensitivity-alleviating medications may be more effective in the treatment of
      DXM-induced GI.

PMID- 29042934
TI  - Intermittent hypoxia simulating obstructive sleep apnea causes pulmonary
      inflammation and activates the Nrf2/HO-1 pathway.
AB  - Obstructive sleep apnea (OSA) is a disorder with high morbidity in adults. OSA
      damages multiple organs and tissues, including the cardiovascular and
      cerebrovascular systems, the metabolism system, the lungs, liver and heart. OSA
      induced damage is earliest and greatest to the pulmonary tissue. The present
      study established a rat OSA model of differing severity by inducing intermittent
      hypoxia with different concentrations of O2 and it was determined that OSA caused
      a severe oxidative stress response and pulmonary inflammation in a dose-dependent
      manner. OSA increased serum levels of C-reactive protein and 8-isoprostane and
      elevated the expression of malondialdehyde, tumor necrosis factor alpha,
      interleukin (IL)-1beta and IL-6 in the pulmonary tissue. Furthermore, the
      expression of two important antioxidants, superoxide dismutase and glutathione,
      was downregulated following intermittent hypoxia. By contrast, levels of
      cylooxygenase 2 and inducible nitric oxide synthase, which are crucial in the
      antioxidative response, increased. In addition, OSA activates the nuclear factor
      erythroid 2-related factor 2 (Nrf2)/heme oxygenase (OH)-1 antioxidative signaling
      pathway. Finally, all increases and decreases in levels of inflammatory and
      antioxidative substances were dependent on oxygen concentrations. Therefore, the
      present study demonstrated that OSA, simulated by intermittent hypoxia, caused an
      oxidative stress response and pulmonary inflammation, and activated the canonical
      antioxidative Nrf2/HO-1 signaling pathway in a dose-dependent manner. These
      results may facilitate the development of clinical therapies to treat pulmonary
      diseases caused by OSA.

PMID- 29042935
TI  - Decreased cathepsin K levels in human atherosclerotic plaques are associated with
      plaque instability.
AB  - Investigating the determinants and dynamics of atherosclerotic plaque instability
      is a key area of current cardiovascular research. Extracellular matrix
      degradation from excessive proteolysis induced by enzymes such as cathepsin K
      (Cat K) is implicated in the pathogenesis of unstable plaques. The current study
      assessed the expression of Cat K in human unstable atherosclerotic plaques.
      Specimens of popliteal arteries with atherosclerotic plaques were classified as
      stable (<40% lipid core plaque area; n=6) or unstable (>=40% lipid core plaque
      area; n=14) based on histopathological examinations of hematoxylin and eosin
      stained sections. The expression of Cat K and cystatin C (Cys C) were assessed by
      immunohistochemical examination and levels of Cat K mRNA were detected by semi
      quantitative reverse transcriptase polymerase chain reaction. Morphological
      changes including a larger lipid core, endothelial proliferation with foam cells
      and destruction of internal elastic lamina were observed in unstable
      atherosclerotic plaques. In unstable plaques, the expression of Cat K protein and
      mRNA was upregulated, whereas Cys C protein expression was downregulated. The
      interplay between Cat K and Cys C may underlie the progression of plaques from
      stable to unstable and the current study indicated that Cat K and Cys C are
      potential targets for preventing and treating vulnerable atherosclerotic plaque
      ruptures.

PMID- 29042936
TI  - The expression of vasohibin-1 and its prognostic significance in bladder cancer.
AB  - Angiogenesis is important in the development of solid tumors. Vasohibin-1 (VASH
      1) is an endothelium-derived protein that acts as an inhibitor of angiogenesis in
      many different types of cancer. However, the expression of VASH-1 and its
      clinical value in bladder cancer remain unknown. The current study analyzed the
      expression of VASH-1, as well as the expression of the angiogenesis-related
      factors vascular endothelial growth factor-A, hypoxia inducible factor-1alpha and
      cluster of differentiation 34 in bladder cancer tissues from 50 patients using
      immunohistochemistry. The associations between the expression of these factors
      and the clinicopathological characteristics of the patients were assessed. The
      current study demonstrated that VASH-1 is primarily expressed in the cytoplasm of
      bladder cancer cells and in a fraction of vascular endothelial cells.
      Furthermore, the expression of VASH-1 was positively associated with the tumor
      stage (P<0.01), pathological grade (P<0.01) and distant metastasis (P<0.05) but
      not with patient age or sex (P>0.05). Spearman rank correlation tests indicated
      that levels of those four factors were positively correlated with each other.
      Kaplan-Meier analysis indicated that high expression of these four factors was
      significantly associated with lower 5-year overall survival and progression-free
      survival rates. Collectively, the results of the current study suggest that VASH
      1 is clinically significant in bladder cancer and its high expression may predict
      the progression and prognosis of patients with bladder cancer. The present study
      also implies that VASH-1 may be a novel target for vascular targeting therapy.

PMID- 29042937
TI  - Inflammation and airway remodeling of the lung in guinea pigs with allergic
      rhinitis.
AB  - Allergic rhinitis (AR) and asthma belong to the category of type I allergic
      diseases, whose pathological features are airway remodeling of the lung and
      allergic inflammation. The aim of the present study was to evaluate inflammation
      and remodeling of lung tissue in a guinea pig model of AR in order to confirm
      consistent pathological changes of upper and lower airways in AR. Male guinea
      pigs were randomly divided into an experimental and a control group (n=10 in
      each). The AR model was established by sensitization through intraperitoneal
      injection of ovalbumin for three weeks and bilateral nasal local excitation for
      twelve weeks. All tissues of nasal mucosa and lung were subjected to hematoxylin
      and eosin as well as toluidine blue staining, and characteristics of remodeling
      of lung tissue, including thickness of bronchial wall, epithelial mucosa and
      smooth muscle were histologically determined. Collagen deposition in lung tissue
      was observed by Masson's trichrome stain. Severe paroxysmal nose scratching
      action, frequent sneezing, visible outflow of secretion from the anterior naris
      and frequent nose friction were observed in the AR model group within 30 min
      after local excitation. The total symptom scores were significantly increased in
      the AR model group compared with those in the control group. Obvious inflammatory
      cell infiltration was observed in the AR model group. Compared with those in the
      control group, the numbers of eosinophils and mast cells in nasal mucosa and lung
      tissue were significantly increased. Obvious airway remodeling of the lung was
      observed in the AR model group. Compared with those in the control group,
      bronchial wall thickness, epithelial layer thickness and smooth muscle thickness
      in the airways were significantly increased in the AR model group. Increased
      collagen deposition was found in the AR model group compared with that in the
      control group. The results of the present study revealed that inflammation and
      airway remodeling of lungs arose in guinea pigs with AR, suggesting that
      pathological changes of upper and lower airways are consistent in this AR model.

PMID- 29042938
TI  - Risk of infection in patients with spondyloarthritis and ankylosing spondylitis
      receiving antitumor necrosis factor therapy: A meta-analysis of randomized
      controlled trials.
AB  - Antitumor necrosis factor (TNF) agents have been widely used for the treatment of
      spondyloarthritis (SpA) and ankylosing spondylitis (AS). However, these agents
      may increase the risk of infection due to suppressing the immune response. The
      present meta-analysis was performed to systematically investigate the risk of
      overall infection, serious infection and tuberculosis in patients with SpA and AS
      treated with anti-TNF agents. Medline, Embase and the Cochrane library were
      searched for randomized controlled trials (RCTs) published between January 1998
      and December 2015 about infection in patients with SpA receiving anti-TNF
      therapy. Data were pooled to obtain relative risks (RRs) along with their 95%
      confidence intervals (CIs). A total of 25 RCTs investigating SpA, including 12
      investigating AS specifically, were eligible for the meta-analysis. Similar risks
      of overall infection were reported in patients with SpA (RR, 1.03; 95% CI, 0.92
      1.15) and AS (RR, 1.06; 95% CI, 0.91-1.24) treated with anti-TNF agents. The RR
      of serious infection for patients with SpA or AS receiving anti-TNF therapy
      compared with a placebo was 1.27 (95% CI, 0.67-2.38) and 1.57 (95% CI, 0.63
      3.91), respectively. In addition, 4 RCTs with outcomes of tuberculosis in
      patients with SpA receiving anti-TNF agents were identified, all in infliximab
      treated patients (RR, 2.52; 95% CI, 0.53-12.09). However, due to the limited
      number of RCTs, this finding should be interpreted with caution. The present meta
      analysis did not find any significantly increased risk of infection associated
      with anti-TNF therapy in patients with SpA or AS. However, due to short duration
      of follow-up in the RCTs and the rarity of serious infections and tuberculosis,
      patients treated with anti-TNF agents still should be closely monitored in
      clinical practice.

PMID- 29042939
TI  - Aphasic status epilepticus as the sole symptom of epilepsy: A case report and
      literature review.
AB  - Aphasia is a common symptom encountered by neurologists. However, the presence of
      aphasia as the sole manifestation of partial status epilepticus is rare. The
      present study reports a case of aphasic status epilepticus in a 27-year-old right
      handed female who presented after the abrupt onset of aphasia, which had
      persisted for 1.5 days. The patient's medical history included head trauma
      followed by a craniectomy and cranioplasty. Computed tomography scans revealed a
      lesion in the patient's left parietal lobe, and an electroencephalogram showed a
      spike and slow wave pattern in the left hemisphere of the brain during aphasia.
      The patient's condition improved after the oral administration of oxcarbazepine
      daily. In the present study it was observed that EEGs were a simple method to
      diagnose aphasic seizures and therefore EEG recordings should be performed in all
      cases of unexplained aphasia. In addition, the present study reviewed previously
      reported cases of aphasic status epilepticus.

PMID- 29042940
TI  - Expression and localization of special AT-rich sequence binding protein 2 in
      murine molar development and the pulp-dentin complex of human healthy teeth and
      teeth with pulpitis.
AB  - Special AT-rich sequence binding protein 2 (SATB2) is a member of the special
      family of AT-rich binding transcription factors and has a critical role in
      osteoblast differentiation and craniofacial patterning. However, the expression
      and distribution of SATB2 in tooth development is largely unknown. The aim of the
      present study was to detect the expression and distribution of SATB2 during
      murine molar development and, in human healthy teeth and teeth with pulpitis
      using immunohistochemistry. Molars were obtained from Kunming mice at embryonic
      day (E) 13.5, E14.5, E16.5 and E18.5, and postnatal day (P) 1, P5 and P7. In
      addition, 20 human teeth (10 healthy and 10 teeth with pulpitis) were obtained
      from young adult patients (age, 24.90+/-1.65 years) who were scheduled for
      routine extraction. Immunohistochemical analyses were performed to detect the
      expression and distribution of SATB2. The present results revealed that SATB2
      exhibits a spatiotemporal expression pattern in murine molar development and was
      expressed in odontoblasts, predentin, dental pulp cells and the blood vessels in
      human teeth. These findings suggested that SATB2 may have an important role in
      odontoblast differentiation and dentin matrix mineralization during tooth
      development.

PMID- 29042941
TI  - Epigallocatechin gallate inhibits the growth and promotes the apoptosis of
      bladder cancer cells.
AB  - Epigallocatechin gallate (EGCG) has been revealed to inhibit the proliferation
      and induce the apoptosis of several types of tumor, in addition to inhibiting DNA
      methyltransferase activity, leading to CpG demethylation. Tissue factor pathway
      inhibitor 2 (TFPI-2) expression is downregulated in bladder cancer. The present
      study revealed that this downregulation was partly due to hypermethylation of the
      TFPI-2 gene promoter, which was decreased by EGCG treatment. In addition, the
      present study demonstrated that EGCG could inhibit the viability and invasion,
      and induce the apoptosis, of bladder cancer T24 cells. Furthermore, western blot
      analysis and reverse transcription-quantitative polymerase chain reaction
      analyses demonstrated that EGCG could upregulate the expression of TFPI-2. These
      results suggest that EGCG inhibits the growth and induces the apoptosis of
      bladder cancer cells through restoring TFPI-2 expression. Thus, EGCG is a
      potential therapeutic candidate for the treatment of bladder cancer.

PMID- 29042942
TI  - Benefits of urethroplasty for managing urethral amyloidosis: A case report.
AB  - Urethral amyloidosis is a rare condition in which eosinophilic amyloid proteins
      are deposited in the urethra. Only a small number of reports on urethral
      amyloidosis have been published. Increased interest has been associated with this
      disease due to its clinical similarities with urothelial carcinoma. A biopsy of
      the lesion and a histological examination are essential for the correct
      diagnosis. Conservative management has been suggested by various urologists as
      the optimal treatment approach for urethral amyloidosis; however, recurrence and
      urethral stricture are common, and typically further treatment is required.
      Urethroplasty has been used in a limited number of urethral amyloidosis cases,
      with beneficial short-term outcomes; however, long-term follow-up data are
      lacking. The present case report describes the cases of 2 patients with urethral
      amyloidosis who underwent urethroplasty without recurrence or progression for >2
      years. These findings indicate that urethroplasty is beneficial for the long-term
      management of urethral amyloidosis.

PMID- 29042943
TI  - Suxiao Jiuxin Pill protects cardiomyocytes against mitochondrial injury and
      alters gene expression during ischemic injury.
AB  - Suxiao Jiuxin Pill (SX), a traditional Chinese medicine compound consisting
      primarily of tetramethylpyrazine and borneol, has been reported to protect
      against ischemic heart disease. However, the effects of SX on mitochondrial
      injury and gene expression in various signaling pathways are unclear. The aim of
      the present study was to investigate the effects of SX on mitochondrial injury
      and to screen the expression of genes potentially altered by SX using a cell
      culture model of ischemic injury. Simulated ischemia was established by culturing
      HL-1 cardiomyocytes in Dulbecco's modified Eagle medium without glucose or serum
      in a hypoxic chamber containing 95% N2 and 5% CO2 for 24 h. HL-1 cardiomyocytes
      were divided into 3 groups: Control, ischemic injury and ischemic injury + SX
      (100 ug/ml; n=3 wells/group). Mitochondrial membrane potential was detected by
      staining with JC-1 dye. The mRNA expression levels of adenylyl cyclase (Adcy) 1
      9, adrenoceptor beta1, Akt1, ATPase Na+/K+ transporting subunit beta2, calcium
      voltage-gated channel auxiliary subunit alpha2delta (Cacna2d)2, Cacna2d3, calcium
      channel voltage-dependent gamma subunit 8, cytochrome C oxidase subunit 6A2
      (Cox6a2), fibroblast growth factor receptor (Fgfr) 4, Fgf8, Fgf12, Gnas complex
      locus, glycogen synthase kinase 3beta (Gsk3b), mitogen-activated protein kinase
      (Mapk)11-14, Mapk kinase kinase kinase 1 (Map4k1), Mas1, nitric oxide synthase 3
      (Nos3), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
      (Pik3ca), phospholipase A2 group 4A, rap guanine nucleotide exchange factor 4 and
      ryanodine receptor 2 were detected using reverse transcription-quantitative
      polymerase chain reaction. The protein expression levels of phosphoinositide 3
      kinase (PI3K), MAS-1 and phosphorylated-endothelial NOS were also examined by
      immunofluorescence staining. The decrease in mitochondrial membrane potential in
      the cell culture model of ischemic injury (P<0.001) was significantly attenuated
      by SX treatment (P<0.001). Furthermore, increases in the mRNA expression levels
      of Adcy2 (P<0.05), 3 (P<0.01) and 8 (P<0.05) in the ischemic injury model were
      significantly attenuated by SX treatment (P<0.01), and SX treatment significantly
      decreased the mRNA expression levels of Adcy1 (P<0.01) and 6 (P<0.05) in ischemic
      cells. Decreases in the mRNA expression levels of Cox6a2 (P<0.001), Gsk3b
      (P<0.01) and Pik3ca (P<0.001) in the ischemic injury model were also
      significantly attenuated by SX treatment (P<0.05, P<0.01 and P<0.001,
      respectively). In addition, the decrease in the protein expression of PI3K
      (P<0.001) was significantly attenuated by SX treatment (P<0.001). The present
      findings indicate that SX may protect cardiomyocytes against mitochondrial injury
      and attenuate alterations in the gene expression of Adcy2, 3 and 8, Cox6a2, Gsk3b
      and Pik3ca during ischemic injury.

PMID- 29042944
TI  - Pien Tze Huang induces apoptosis and inhibits proliferation of 5-fluorouracil
      resistant colorectal carcinoma cells via increasing miR-22 expression.
AB  - The well-known traditional Chinese medicine formula Pien Tze Huang (PZH) has long
      been used to treat various malignancies, including colorectal cancer (CRC). It
      was recently reported that PZH possesses the ability to overcome multidrug
      resistance in CRC cells. In the present study, a 5-fluorouracil (5-FU) resistant
      human CRC cell line (HCT-8/5-FU) was used to further evaluate the effect of PZH
      on chemotherapy (chemo)-resistance and investigate the mechanisms through which
      this occurs. The results identified that PZH significantly reduced the viability
      and cell density of HCT-8/5-FU cells in a dose- and time-dependent manner
      (P<0.05). PZH inhibited cell survival, reduced the proportion of cells in S
      phase, and suppressed the expression of pro-proliferative proteins cyclin D1 and
      cyclin-dependent kinase 4. In addition, PZH treatment induced nuclear
      condensation and fragmentation, activated caspase-9 and -3 and increased the pro
      apoptotic Bcl-2-associated X protein/B-cell lymphoma 2 protein ratio.
      Furthermore, PZH treatment upregulated the expression of microRNA-22 (miR-22) and
      downregulated the expression of c-Myc (a target gene of miR-22). In conclusion,
      the findings from the present study suggest that PZH can overcome chemo
      resistance in cancer cells, likely through increasing miR-22 expression, and by
      reversing the imbalance between levels of proliferation and apoptosis.

PMID- 29042945
TI  - Human umbilical cord mesenchymal stem cells increase interleukin-9 production of
      CD4+ T cells.
AB  - Mesenchymal stem cells (MSC) are able to differentiate into cells of multiple
      lineage, and additionally act to modulate the immune response. Interleukin (IL)-9
      is primarily produced by cluster of differentiation (CD)4+ T cells to regulate
      the immune response. The present study aimed to investigate the effect of human
      umbilical cord derived-MSC (UC-MSC) on IL-9 production of human CD4+ T cells. It
      was demonstrated that the addition of UC-MSC to the culture of CD4+ T cells
      significantly enhanced IL-9 production by CD4+ T cells. Transwell experiments
      suggested that UC-MSC promotion of IL-9 production by CD4+ T cells was dependent
      on cell-cell contact. Upregulated expression of CD106 was observed in UC-MSC co
      cultured with CD4+ T cells, and the addition of a blocking antibody of CD106
      significantly impaired the ability of UC-MSC to promote IL-9 production by CD4+ T
      cells. Therefore, the results of the present study demonstrated that UC-MSC
      promoted the generation of IL-9 producing cells, which may be mediated, in part
      by CD106. The findings may act to expand understanding and knowledge of the
      immune modulatory role of UC-MSC.

PMID- 29042946
TI  - The effects of Y-shaped conchal cartilage transplantation on the correction of
      nasal deformity secondary to cleft lip and its influence on mental health.
AB  - Patients who undergo corrective surgery for cleft lip are known to be at risk for
      subsequently developing secondary nasal deformity. The aim of this study was to
      investigate the effects of Y-shaped conchal cartilage transplantation on the
      correction of nasal deformity secondary to cleft lip and its influence on mental
      health. Sixteen patients with nasal deformity secondary to cleft lip admitted to
      The First People's Hospital Xuzhou (Xuzhou, China) from February 2014 to February
      2015 were selected for the study. Conchal cartilage was taken from the patients
      and made into a Y-shaped stent, which was then transplanted into the nasal
      columella. The surgical outcomes and patient satisfaction were evaluated and HADS
      was used to compare the preoperative and postoperative mental health. After the
      affected side of the nose was corrected, the nasal profiles of 12 patients were
      significantly improved, the height of nasal columella and nostril was
      significantly increased, the nasal base and breadth were significantly shorter
      than those before operation and the nose wing-nasal breadth index on the affected
      side was significantly increased compared to that before operation and the
      differences were statistically significant (P<0.05). The satisfaction of each
      index after the operation was more than 90%. The mental health of patients after
      operation was notably improved compared to before operation and the difference
      was statistically significant (P<0.05). After the correction of secondary nasal
      deformity to cleft lip through Y-shaped conchal cartilage transplantation, the
      shape of the nasal tip was stable without the recurrence of deformities or
      distortion on the donor site of the auricle. Y-shaped conchal cartilage
      transplantation is an ideal treatment method for the moderate and severe
      secondary nasal deformity to cleft lip and effective perioperative mental
      intervention can improve the patient's mental health status, an outcome that is
      worth popularizing in clinical applications.

PMID- 29042947
TI  - miR-124 inhibits proliferation, migration and invasion of malignant melanoma
      cells via targeting versican.
AB  - MicroRNA (miR)-124 has been implicated in malignant melanoma (MM). However, the
      detailed regulatory mechanism of miR-124 in the malignant phenotypes of MM cells
      has remained largely elusive. A total of 68 pairs of MM tissues and adjacent
      tissues were collected. Reverse-transcription quantitative polymerase chain
      reaction was used to examine the mRNA expression of versican as well as the
      expression of miR-124, and the protein expression of versican was assessed by
      western blot analysis. MTT, wound healing and Transwell assays were used to
      determine cell proliferation, migration and invasion, respectively. A
      bioinformatics analysis and a luciferase reporter assay were used to confirm the
      targeting association between miR-124 and versican. miR-124 was significantly
      downregulated in MM tissues compared with that in adjacent non-tumorous tissues,
      and decreased expression of miR-124 was associated with increased tumor
      thickness, advanced clinical stage and node metastasis of MM. Furthermore, the
      expression levels of miR-124 were also reduced in MM cell lines compared with
      normal human skin HACAT cells. Forced overexpression of miR-124 caused a
      significant reduction in the proliferation, migration and invasion of MM A375
      cells. Versican was significantly upregulated in MM tissues and cell lines, and
      was identified as a novel target of miR-124 in A375 cells using a luciferase
      reporter gene assay, and miR-124 was revealed to negatively regulate the protein
      expression of versican in A375 cells. Overexpression of versican impaired the
      suppressive effects of miR-124 on the proliferation, migration and invasion of
      A375 cells. In conclusion, miR-124 inhibited the malignant phenotypes of MM cells
      at least partly via inhibition of versican. Therefore, the miR-124/versican axis
      may be used as a promising therapeutic target for inhibiting MM growth and
      metastasis.

PMID- 29042949
TI  - Angina in granulomatosis with polyangiitis: A case report.
AB  - Granulomatosis with polyangiitis (GPA) often causes small blood vessel lesions in
      multiple organs, with less impact on large vessels. We report a case involving
      not only large blood vessels, but also angina. The computed tomographic
      angiography of large vessels and vascular ultrasonography of the extremity also
      suggested great arteries of the body were involved. Further cytoplasmic
      antineutrophil cytoplasmic antibody tests, pathological examination and dynamic
      chest computed tomography scan confirmed the diagnosis of GPA. Anti-inflammatory
      therapy and coronary secondary prevention were given after diagnosis by
      pathological examination and laboratory evaluation. The symptoms of angina
      pectoris were relieved. This rare case report reminds us that among the well
      known risk factors of atherosclerotic diseases, GPA is also an important risk
      factor for acute coronary syndrome. Early foresight for this rare risk factor can
      improve the early diagnosis and treatment of the disease, which will improve the
      prognosis of the patients.

PMID- 29042948
TI  - The efficacy of radiofrequency ablation in the treatment of pediatric arrhythmia
      and its effects on serum IL-6 and hs-CRP.
AB  - The aim of this study was to investigate the efficacy of radiofrequency ablation
      in the treatment of pediatric arrhythmia and to assess the changes in serum
      interleukin-6 (IL-6) and hs-CRP levels after treatment. Hundred and six children
      with tachyarrhythmia who were admitted to Xuzhou Children's Hospital from
      November, 2014 to December, 2015 were recruited for study. The efficacies of
      radiofrequency in the treatment of different types of arrhythmia were analyzed.
      Successful ablation was found in 104 cases (98.11%) and recurrence was found in 7
      cases (6.73%). Among 62 cases of atrioventricular reentrant tachycardia (AVRT),
      successful ablation was found in 60 cases (96.77%) and recurrence was found in 3
      cases (4.84%). Among 33 cases of atrioventricular nodal reentrant tachycardia
      (AVNRT), successful ablation was found in 33 cases (100%) and recurrence was
      found in 2 cases (6.06%). Among 5 cases of ventricular tachycardia (VT),
      successful ablation was found in 5 cases (100%) and no recurrence was found.
      Among 4 cases of atrial tachycardia (AT), successful ablation was found in 4
      cases (100%) and recurrence was found in 1 case (25%). Among 2 cases of atrial
      flutter (AFL), successful ablation was found in both (100%) and recurrence was
      found in 1 case (50%). After operation, the levels of IL-6 and hs-CRP were
      increased and were continually increased within 6 h after operation. The levels
      of IL-6 and hs-CRP at 24 h after operation were reduced but still higher than
      preoperative levels. The duration of radiofrequency and ablation energy were
      positively correlated with the levels of IL-6 and hs-CRP, while the number of
      discharges was not significantly correlated with either. In conclusion,
      radiofrequency ablation is a safe and effective treatment for pediatric
      arrhythmia. Postoperative monitoring of IL-6 and hs-CRP levels is conducive to
      understanding postoperative myocardial injury and inflammatory response.

PMID- 29042950
TI  - Expression of CCR3, SOX5 and LC3 in patients with elderly onset rheumatoid
      arthritis and the clinical significance.
AB  - This study investigated the expression of C-C chemokine receptor type 3 (CCR3),
      transcription factor SOX5 (SOX5) and microtubule-associated protein 1 light chain
      3 (LC3) in patients with elderly onset rheumatoid arthritis (EORA) and the
      clinical significance. Ninety patients with elderly onset rheumatoid arthritis
      were selected in our hospital from January to December in 2016 to serve as
      patient group. At the same time, 50 healthy people were selected as control
      group. Levels of CCR3, SOX5 and LC3 in serum of two groups were detected by
      enzyme-linked immunosorbent assay (ELISA). Expression levels of CCR3, SOX5 and
      LC3 mRNA in peripheral blood mononuclear cells (PBMCs) were detected by reverse
      transcription-PCR (RT-PCR). Expression level of CCR3 mRNA in patient group was
      0.752+/-0.054, which was significantly higher than that in control group (0.287+/
      0.032, t=8.932, P<0.05). Levels of CCR3, SOX5 and LC3 in serum of patients in
      patient group were significantly higher than those in control group (P<0.05).
      Positive correlations were found between serum levels of CCR3 and SOX5 (r=0.613,
      P<0.05), serum levels of CCR3 and LC3 (r=0.637, P<0.05), and serum levels of SOX5
      and LC3 (r=0.645, P<0.05). CCR3, SOX5 and LC3 are highly expressed in PBMC and
      serum, which may be closely related to the occurrence and development of EORA.
      These indexes may be used as indicators of clinical diagnosis and prognosis of
      patients with EORA.

PMID- 29042951
TI  - Ursolic acid suppresses TGF-beta1-induced quiescent HSC activation and
      transformation by inhibiting NADPH oxidase expression and Hedgehog signaling.
AB  - Activation of quiescent hepatic stellate cells (q-HSCs) and their transformation
      to myofibroblasts (MFBs) is a key event in liver fibrosis. Hedgehog (Hh)
      signaling stimulates q-HSCs to differentiate into MFBs, and NADPH oxidase (NOX)
      may be involved in regulating Hh signaling. The author's preliminary study
      demonstrated that ursolic acid (UA) selectively induces apoptosis in activated
      HSCs and inhibits their proliferation in vitro via negative regulation of NOX
      activity and expression. However, the effect of UA on q-HSCs remains to be
      elucidated. The present study aimed to investigate the effect of UA on q-HSC
      activation and HSC transformation and to observe alterations in the NOX and Hh
      signaling pathways during q-HSC activation. q-HSC were isolated from adult male
      Sprague-Dawley rats. Following culture for 3 days, the cells were treated with or
      without transforming growth factor-beta1 (TGF-beta1; 5 ug/l); intervention groups
      were pretreated with UA (40 uM) or diphenyleneiodonium chloride (DPI; 10 uM) for
      30 min prior to addition of TGF-beta1. mRNA and protein expression of NOX and Hh
      signaling components and markers of q-HSC activation were examined by western
      blotting and reverse transcription-polymerase chain reaction. TGF-beta1 induced
      activation of q-HSCs, with increased expression of alpha-smooth muscle actin
      (alpha-SMA) and type I collagen. In addition, expression of NOX subunits
      (gp91phox, p67phox, p22phox, and Rac1) and Hh signaling components, including
      sonic Hh, sterol-4-alpha-methyl oxidase, and Gli family zinc finger 2, were
      upregulated in activated HSCs. Pretreatment of q-HSCs with UA or DPI prior to TGF
      beta1 significantly downregulated expression of NOX subunits and Hh signaling
      components and additionally inhibited expression of alpha-SMA and type I
      collagen, thereby preventing transformation to MFBs. UA inhibited TGF-beta1
      induced activation of q-HSCs and their transformation by inhibiting expression of
      NOX subunits and the downstream Hh pathway.

PMID- 29042952
TI  - Protective effect of ulinastatin on severe pulmonary infection under
      immunosuppression and its molecular mechanism.
AB  - The objective of the present study was to investigate the protective effect of
      ulinastatin on severe pulmonary infection under immunosuppression, and its
      molecular mechanism. Mice were treated with methylprednisolone and
      lipopolysaccharide (LPS) to establish the model of severe pulmonary infection
      under immunosuppression. Mice were randomly divided into group A (model group;
      treated with equal volumes of saline), group B (treated with 1*105 U/kg
      ulinastatin), and group C (normal control group). Bronchoalveolar lavage fluid
      (BALF) was collected, and the concentrations of cytokines in BALF were measured
      by enzyme-linked immunosorbent assay (ELISA). Pathological changes in lung
      tissues were observed by hematoxylin and eosin (H&E) staining. The mRNA levels of
      M1 and M2 macrophage markers in lung tissues were detected by real-time
      polymerase chain reaction (PCR). Specific protein levels in lung tissues were
      measured by western blotting. Apoptosis in lung tissues was detected by the
      terminal-deoxynucleoitidyl transferase mediated nick end-labeling (TUNEL) method.
      The concentrations of TNF-alpha, IL-6, and IL-1beta in BALF, the mRNA levels of
      the three M1 macrophage markers, and the protein levels of p-Janus Kinase 2 (p
      JAK2), p-signal transducer and activator of transcription-3 (p-STAT-3), cleaved
      caspase-9, and cleaved poly-ADP-ribose polymerase (PARP), and the number of
      apoptotic cells in lung tissues in group A were significantly higher than those
      in groups B and C (P<0.05), whereas the concentrations of IL-4, IL-10, and IL-13
      and the mRNA levels of the three M2 macrophage markers were significantly lower
      than those in groups B and C (P<0.05). Immunofluorescence showed that the nuclei
      of lung epithelial macrophages in group A became smaller and moved towards the
      side of nuclear membranes. In conclusion, ulinastatin can improve the
      inflammatory response caused by severe infection under immunosuppression, which
      balances the inflammatory microenvironment and inhibits apoptosis at least
      partially through inhibiting JAK2/STAT-3 and/or caspase pathway activity,
      ultimately playing a role in lung protection.

PMID- 29042953
TI  - Oral colon-specific drug delivery system reduces the nephrotoxicity of rhubarb
      anthraquinones when they produce purgative efficacy.
AB  - Rhubarb is commonly used to treat constipation in China and anthraquinones (AQs)
      are the active components present in rhubarb. However, an increasing number of
      studies have reported that AQs induce nephrotoxicity. In the present study,
      rhubarb total free anthraquinones (RTFA) oral colon-specific drug delivery
      granules (RTFA-OCDD-GN) were prepared to determine whether RTFA-OCDD-GN could
      reduce the nephrotoxicity that occurs when AQs produce purgative efficacy. RTFA
      OCDD-GN were prepared using pH-enzyme double-layer coating technology and the
      cumulative release rate of RTFA in RTFA-OCDD-GN was assessed. The first black
      stool time, the number and state of feces over 8 h were observed to measure the
      purgative efficacy. In the nephrotoxicity test, biochemical and histopathological
      examinations were performed following 20 and 40 days administration, and 20 days
      convalescence. The cumulative release rate of RTFA in RTFA-OCDD-GN was >80% in
      simulated colonic fluid. RTFA-OCDD-GN produced considerable purgative efficacy
      compared with rhubarb medical material samples (RMMS). Following 40 days RMMS
      administration, blood urea nitrogen, creatinine and urine beta2-microglobulin
      levels in the high-dosage group were significantly increased compared with the
      control and RTFA-OCDD-GN groups (P<0.05). All specimens from the high-dosage RMMS
      group exhibited swelling/degeneration of renal proximal convoluted tubule
      epithelial cells. No difference in pathological conditions and biochemical
      indicators was detected between the RTFA-OCDD-GN groups and the control group.
      The nephrotoxicity of AQs was significantly reduced following RTFA-OCDD-GN
      administration, which produced considerable purgative efficacy compared with
      RMMS.

PMID- 29042954
TI  - Dexmedetomidine ameliorates the inflammatory immune response in rats with acute
      kidney damage.
AB  - It has been demonstrated that dexmedetomidine (Dex) can protect patients with
      acute kidney injury from experiencing further tissue damage, however its
      mechanism of action remains unclear. The present study investigated the immune
      modulatory functions of Dex in rats with acute kidney injury (AKI) induced via
      injection of lipopolysaccharide into the tail vein. ELISA analysis showed that
      Dex reduced the levels of inflammatory cytokines in rats with AKI in a dose
      dependent manner. Furthermore, the regulatory effects of Dex on cytokine
      production disappeared when the alpha-2 adrenergic receptor antagonist Yohimbine
      (YOH) was added. For a detailed investigation on how Dex regulates the immune
      response in rats with AKI, the impact of Dex on the viability of splenocytes and
      lymphocytes was determined and it was determined that Dex did not influence
      splenocyte and lymphocyte viability. In addition, ELISA tests showed that Dex
      regulated the production of the T-helper (Th) 17 cytokines interleukin (IL)-17
      and IL-23, but not the Th1 cytokine tumor necrosis factor alpha, in splenocytes
      and lymphocytes. To confirm whether Dex functioned as an alpha-2-adrenergic
      receptor in these immune regulations, YOH was administered together with Dex.
      When Dex and YOH were administered together, the regulatory functions of Dex were
      reduced, confirming that Dex acted as an agonist on the alpha-2-adrenergic
      receptor. Thus the results of the current study may provide novel insights
      regarding how Dex modulates immune functions in AKI.

PMID- 29042955
TI  - Intramyocardial delivery of bFGF with a biodegradable and thermosensitive
      hydrogel improves angiogenesis and cardio-protection in infarcted myocardium.
AB  - Basic fibroblast growth factor (bFGF), a known angiogenic factor, may provide a
      potential strategy for the treatment of myocardial infarction (MI), but it is
      limited by a relatively short half-life. Dex-PCL-HEMA/PNIPAAm hydrogel provides a
      reservoir for the controlled release of growth factors. The aim of the current
      study was to evaluate the effects of bFGF incorporated into a Dex-PCL
      HEMA/PNIPAAm hydrogel on angiogenesis and cardiac health in a rat model of acute
      MI, induced by coronary artery ligation. Phosphate-buffered solution (PBS group),
      Dex-PCL-HEMA/PNIPAAm hydrogel (Gel group), bFGF in phosphate-buffered solution
      (bFGF group) or bFGF in hydrogel (Gel + bFGF group) was injected into a peri
      infarcted area of cardiac tissue immediately following MI. On day 30 post
      surgery, cardiac function was assessed by echocardiography, apoptosis index by
      terminal deoxynucleotidyl transferase dUTP nick-end labeling assessment and
      vascular development by immunohistochemical staining. The findings demonstrated
      that injection of bFGF along with hydrogel induced angiogenesis, reduced collagen
      content, MI area and cell apoptosis and improved cardiac function compared with
      the injection of either bFGF or hydrogel alone. bFGF incorporated with Dex-PCL
      HEMA/PNIPAAm hydrogel injection induces angiogenesis, attenuates cardiac
      remodeling and improves cardiac function following MI.

PMID- 29042957
TI  - Ursolic acid inhibits breast cancer growth by inhibiting proliferation, inducing
      autophagy and apoptosis, and suppressing inflammatory responses via the PI3K/AKT
      and NF-kappaB signaling pathways in vitro.
AB  - Breast cancer, which is the second leading cause of cancer-associated mortality
      in women worldwide, develops from breast tissue. Chemotherapy is the most
      commonly used therapy to treat breast cancer. However, a number of natural plant
      derived products have been suggested as alternative therapies to treat different
      types of cancer, such as breast cancer. The aim of the present study was to
      determine the anti-tumor effects of ursolic acid and its effect on apoptosis and
      inflammation in breast cancer cells. The anti-cancer effects of ursolic acid were
      evaluated in vitro using flow cytometry, western blotting and reverse
      transcription-quantitative polymerase chain reaction. The results suggest that
      ursolic acid inhibits the viability of breast cancer cells by inducing autophagy
      and apoptosis without inducing cell death. Cellular migration assays demonstrated
      that ursolic acid was able to suppress the invasive ability of breast cancer
      cells (P<0.05). In addition, the phosphoinositide 3-kinase (PI3K)/protein kinase
      B (AKT) pathway was downregulated following ursolic acid administration (P<0.05),
      leading to an upregulation of glycogen synthase kinase activity (P<0.05) and
      downregulation of B-cell lymphoma 2 (P<0.05), subsequently causing autophagy and
      apoptosis via cyclin-D1 inhibition and caspase-3 stimulation (P<0.05).
      Furthermore, the inflammatory response of breast cancer cells was assessed by
      measuring levels of nuclear factor (NF)-kappaB. Ursolic acid was found to
      downregulate NF-kappaB in breast cancer cells, thus inhibiting inflammation and
      preventing the progression of breast cancer (P<0.05). To the best of our
      knowledge, the present study is the first to assess the effect of ursolic acid on
      breast cancer cells through PI3K/AKT-regulated GSK and caspase-3 accompanied by
      NF-kappaB signaling pathways. The results of the present study regarding the
      potential underlying molecular mechanisms of ursolic acid may be used to develop
      novel therapeutic strategies for breast cancer treatment.

PMID- 29042956
TI  - Evaluation of the hemodynamics and right ventricular function in pulmonary
      hypertension by echocardiography compared with right-sided heart catheterization.
AB  - The present study aimed to evaluate hemodynamics and right ventricular function
      in patients with pulmonary hypertension (PH) using transthoracic echocardiography
      and to compare these results with measurements obtained using right-sided heart
      catheterization (RHC). A total of 75 patients with PH were examined using
      echocardiography and RHC. Patients were divided into the following two groups
      according to their difference between SPAPecho and SPAPRHC measurement: The
      overestimated group and underestimated group. The overestimated group included
      the subgroups groupover-A (difference <20 mmHg) and groupover-B (difference >=20
      mmHg), and the underestimated group included groupunder-A (absolute value of the
      difference <20 mmHg) and groupunder-B (absolute value of the difference >=20
      mmHg). SPAPecho measurements were revealed to be significantly positively
      correlated with SPAPRHC measurements (r=0.794; P<0.01). Among all
      echocardiographic measurements, only tricuspid annular plane systolic excursion
      (TAPSE) was significantly different between groups; it was increased in groupover
      A and groupunder-A compared with groupover-B (P<0.01). Although SPAP measurements
      obtained using echocardiography were significantly positively correlated with
      those obtained using RHC, a high proportion of overestimation or underestimation
      of SPAP by echocardiography remained.

PMID- 29042958
TI  - Expression of LOX-1 in human mesangial cells is increased by Ox-LDL and IL-1beta
      treatment.
AB  - The present study aimed to determine whether the expression of lectin-like
      oxidized LDL receptor 1 (LOX-1) could be induced by oxidized low-density
      lipoprotein (Ox-LDL) and interleukin 1beta (IL-1beta) in human mesangial cells
      (HMCs). Oil Red O staining was used to observe the uptake of Ox-LDL by HMCs
      stimulated with IL-1beta, and reverse transcription-quantitative polymerase chain
      reaction analysis and western blotting were used to examine the expression of LOX
      1 in HMC following Ox-LDL and IL-1beta treatment. Uptake of Ox-LDL by HMCs was
      upregulated upon stimulation with IL-1beta. Furthermore, Ox-LDL (10-40 ug/ml)
      treatment induced LOX-1 mRNA and protein expression in a dose-dependent manner.
      In addition, when HMCs were treated with IL-1beta and Ox-LDL, the expression of
      LOX-1 was enhanced further. These results indicated that inhibiting LOX-1
      expression or inhibiting the Ox-LDL/LOX-1 signaling axis may be a potential novel
      method for treating renal disease.

PMID- 29042959
TI  - Diagnosis of cobalamin C deficiency with renal abnormality from onset in a
      Chinese child by next generation sequencing: A case report.
AB  - The aim of the present study was to present the diagnosis and treatment course of
      a patient with cobalamin C deficiency (cblC) hospitalized with renal function
      abnormality from the onset. A female, 7-year-old patient who presented with a
      cough and progressive dyspnea for 1 day was admitted to the Children's Hospital
      of Nanjing Medical University (Nanjing, China). A routine clinical examination
      was performed, including physical examination, routine blood and urine tests,
      blood gas analysis, computed tomography scans of the head, chest and abdomen,
      electrocardiogram, echocardiography and abdominal ultrasonography. In addition,
      laboratory tests were performed, including tests for viral infection and markers
      of autoimmunity, humoral immunity, myocardial enzymes and tumors. Tandem mass
      analysis and renal biopsy were conducted. Next generation sequencing (NGS) was
      performed to identify mutated genes, and structural investigation was conducted
      to identify the key residue mutations in the patient. Routine clinical
      examination revealed that the patient had multiple organ failure, indicating the
      presence of metabolic disease. Tandem mass analysis and renal biopsy also
      indicated that the patient had methylmalonic acidemia (MMA) and thrombotic
      microangiopathy combined with focal renal cortical necrosis. Furthermore, next
      generation sequencing identified the presence of two heterozygous mutations in
      the MMA cblC type with homocystinuria (MMACHC) gene. Structural analysis
      demonstrated that the two mutations were in key components of the MMACHC protein.
      The patient was finally diagnosed with cblC according to the results obtained. In
      conclusion, NGS may aid in the diagnosis and therapeutic management of cblC with
      renal abnormality from the onset in children.

PMID- 29042960
TI  - Application of 3D printing rapid prototyping-assisted percutaneous fixation in
      the treatment of intertrochanteric fracture.
AB  - The aim of the present study was to investigate the application of 3D printing
      (3DP) rapid prototyping (RP) technique-assisted percutaneous fixation in the
      treatment of femoral intertrochanteric fracture (ITF) using proximal femoral nail
      anti-rotation (PFNA). A total of 39 patients with unstable ITF were included in
      the current study. Patients were divided into two groups: 19 patients were
      examined using computed tomography scanning and underwent PFNA with SDP-RP
      whereas the other 20 patients underwent conventional PFNA treatment. Anatomical
      data were converted from the Digital Imaging and Communications in Medicine
      format to the stereolithography format using M3D software. The 3DP-RP model was
      established using the fused deposition modeling technique and the length and
      diameter of the main screw blade was measured during the simulation. The
      postoperative femoral neck-shaft angle (NSA), surgery duration, intraoperative
      and postoperative blood loss, and the duration of hospital stay were recorded and
      compared with the corresponding values in conventional surgery. No significant
      differences were observed in mean PFNA size between the implants used and the
      preoperative planning estimates. It was demonstrated that the 3DP-RP assisted
      procedure resulted in more effective reduction of the NSA. Furthermore, patients
      undergoing 3DP-RP experienced a significant reduction in duration of surgery
      (P<0.01), as well as reductions in intraoperative (P=0.02) and postoperative
      (P=0.03) blood loss, compared with conventional surgery. At 6 months post
      surgery, no cases of hip varus/vague deformities or implant failure were observed
      in patients that underwent either the 3DP-RP-assisted or conventional procedure.
      The results of the present study suggest that the 3DP-RP technique is able to
      create an accurate model of the ITF, which facilitates surgical planning and
      fracture reduction, thus improving the efficiency of PFNA surgery for ITFs.

PMID- 29042961
TI  - The long non-coding RNA AK023948 enhances tumor progression in hepatocellular
      carcinoma.
AB  - The long non-coding RNAs (lncRNAs) have been demonstrated to play pivotal roles
      in a broad range of processes including tumor biology. However, the exact
      contributions of lncRNAs to hepatocellular carcinoma (HCC) remain poorly defined.
      In current study, we have unraveled a novel function of AK023948 in HCC. We found
      that AK023948 was substantially upregulated in tumor tissues. Meanwhile, higher
      AK023948 expression correlated with poor survival. Upregulation of AK023948
      expression can promote HepG2 and Hep3B proliferation and invasion in in vitro
      experiments. Furthermore, AK023948 also decreased tumor growth in vivo. The
      tumorigenic role of AK023948 was partially ascribed to PI3K/Akt/mTOR signaling
      and AK023948 knockdown decreased pathway activation and tumor growth. These data
      collectively suggest an oncogenic role for AK023948 and may provide potential
      insight into therapeutic intervention.

PMID- 29042962
TI  - MicroRNA-138 directly targets TNFAIP8 and acts as a tumor suppressor in
      osteosarcoma.
AB  - MicroRNAs (miRs) have a critical role in the development and malignant
      progression of osteosarcoma (OS), but the underlying mechanisms have largely
      remained elusive. The present study aimed to explore the regulatory role of miR
      138 in OS growth and metastasis and investigated the associated mechanisms.
      Reverse-transcription quantitative polymerase chain reaction and western blot
      analysis were performed to examine the miR-138 and protein expression levels in
      OS and normal bone tissues and cell lines. An MTT assay and a Transwell assay
      were used to assess cell proliferation and invasion. Flow cytometry was used to
      analyze the cell cycle and determine the apoptotic rate. A luciferase reporter
      assay was used to confirm the targeting association between miR-138 and tumor
      necrosis factor-alpha-induced protein 8 (TNFAIP8). It was found that miR-138 was
      downregulated in OS tissues and cell lines. Overexpression of miR-138 decreased
      the proliferation, cell cycle progression and invasion of OS cells, while
      inducing cell apoptosis. TNFAIP8 was then identified as a novel target of miR
      138. Similarly to the effects of miR-138 overexpression, inhibition of TNFAIP8
      also inhibited OS cell proliferation, cell cycle progression and invasion, and
      induced cell apoptosis. In addition, miR-138 overexpression as well as
      downregulation of TNFAIP8 reduced OS cell invasion via inhibition of matrix
      metalloproteinase-2 and -9 expression. Taken together, the results of the present
      study demonstrated that miR-138 directly targets TNFAIP8 and acts as a tumor
      suppressor in OS, suggesting that the miR-138/TNFAIP8 interaction may become a
      promising therapeutic target for OS.

PMID- 29042963
TI  - Warm sparse-dense wave inhibits cartilage degradation in papain-induced
      osteoarthritis through the mitogen-activated protein kinase signaling pathway.
AB  - Cartilage degradation is an important in the pathogenesis of osteoarthritis (OA).
      Abnormal activation of the mitogen-activated protein kinase (MAPK) signaling
      pathway in chondrocytes promotes an inflammatory response, resulting in the
      release of chondral matrix-degrading enzymes that accelerate the degradation of
      cartilage. As a non-pharmaceutical and non-invasive physical therapy regimen,
      warm sparse-dense wave (WSDW) has been successfully used for the treatment of OA.
      However, it remains unclear whether WSDW inhibits cartilage degradation in OA
      through the MAPK signaling pathway. The present study investigated the effects of
      WSDW on papain-induced OA in rat knee joints. Papain-induced OA was established
      in rats, which were subsequently divided into a model group and three
      experimental groups that received a WSDW with the following ratios: WSDW=1:1,
      WSDW=1:2 and WSDW=2:1. After 12 weeks of treatment, cartilage degradation was
      evaluated by Mankin scoring of paraffin-embedded sections stained with
      hematoxylin and eosin. The changes in cartilage structure were observed by
      transmission electron microscopy, and the expressions of RAS, extracellular
      signal-regulated kinase (ERK), p38 and p53 were measured by reverse transcription
      quantitative polymerase chain reaction and western blot analysis. WSDW was
      demonstrated to improve the arrangement of collagen fibers, inhibit the tidemark
      replication and delay cartilage degradation in papain-induced OA. The expressions
      of RAS, ERK, p38 and p53 in the WSDW (1:2) and (2:1) groups were significantly
      decreased when compared with the model group (P<0.01). Furthermore, amongst the
      WSDW groups, the inhibitory effects of the WSDW (1:2) group were typically
      greater than those of the WSDW (1:1) and (2:1) groups. The results indicate that
      WSDW may inhibit cartilage degradation in papain-induced OA in rat knee joints by
      regulating the MAPK signaling pathway.

PMID- 29042964
TI  - In utero repair of fetal rat myelomeningocele affects neuromuscular development
      in the bladder.
AB  - Fetal repair of myelomeningocele (MMC) has been proven to be beneficial for the
      central nervous system development; however, the effect of fetal MMC repair on
      bladder function remains controversial. The objective of the present study was to
      establish an early timepoint for in utero MMC repair using a rat model, and to
      investigate the changes in bladder development subsequent to that intervention.
      Sprague Dawley rats were divided into the MMC, MMC repair and control groups. MMC
      rat fetus models were created by treating pregnant rats with all-trans retinoic
      acid. The MMC defect was then repaired in utero at embryonic day 17 (E17) using a
      chitosan-gelatin membrane patch. Fetal rat bladders were removed at E19 and E21
      in each group, as well as at stage E17 in the MMC and control groups.
      Differential expression of beta-III-tubulin, alpha-smooth muscle actin (alpha
      SMA), nerve growth factor (NGF) and acetylcholinesterase (AChE) mRNA, and beta
      III-tubulin and alpha-SMA protein in the bladder following fetal repair was
      measured and compared among the three groups. In addition, the expression of NGF
      mRNA was significantly elevated at E21 in the MMC group compared with that of the
      control group, however, the level decreased in the repair group at stage E21. The
      expression of alpha-SMA mRNA significantly increased at E19 and then decreased at
      E21 in the repair group compared with that of the MMC group; however, there were
      no significant changes in alpha-SMA protein following the repair. Furthermore,
      the repair enhanced beta-III-tubulin mRNA expression at E19, but ameliorated the
      decrease of beta-III-tubulin protein at E21. The expression of AChE mRNA
      increased in the MMC group at E19 and E21 compared with that of the control
      group, although it was not significantly altered following repair as compared
      with that of the MMC group. In conclusion, in the current study, abnormal
      neuromuscular development was observed in the MMC bladder, which enabled a
      certain degree of improvement in the in utero MMC repair.

PMID- 29042965
TI  - Overexpression of let-7a increases neurotoxicity in a PC12 cell model of
      Alzheimer's disease via regulating autophagy.
AB  - Increased deposition of beta-amyloid (Abeta) protein is one of the typical
      characteristics of Alzheimer's disease (AD). Recent evidence has demonstrated
      that the microRNA let-7 family, which is highly expressed in the central nervous
      system, participates in the regulation of pathologic processes of AD. In the
      present study, the effect of let-7a overexpression on Abeta1-40-induced
      neurotoxicity was evaluated in PC12 and SK-N-SH cells. The results indicated that
      overexpression of let-7a enhanced the neurotoxicity induced by Abeta1-40 in PC12
      and SK-N-SH cells. In addition, the apoptosis induced by Abeta1-40 in PC12 and SK
      N-SH cells was increased by let-7a overexpression. Furthermore, Abeta1-40
      treatment increased the protein levels of microtubule-associated protein 1A/1B
      light chain 3 (LC3) and beclin-1 and increased the LC3 II/I ratio. The mRNA
      expression levels of beclin-1, autophagy protein 5 (Atg-5) and Atg-7 were also
      increased by Abeta1-40 treatment in PC12 cells. Let-7a overexpression further
      upregulated the above autophagy-related markers. Furthermore, the protein level
      of p62 was increased by Abeta1-40 treatment, and this was further enhanced by let
      7a overexpression. Finally, the present results demonstrated that the
      phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR)
      signaling pathway was involved in the autophagy regulation by let-7a. In
      conclusion, the present study demonstrates that the neurotoxicity induced by
      Abeta1-40 is augmented by let-7a overexpression via regulation of autophagy, and
      the PI3K/Akt/mTOR signaling pathway also serves a function in this process.

PMID- 29042966
TI  - Effects of RPE-conditioned medium on the differentiation of hADSCs into RPE
      cells, and their proliferation and migration.
AB  - Age-related macular degeneration (AMD) is associated with the dysfunction and
      death of the retinal pigment epithelium (RPE). Recently, there has been
      increasing interest in stem cell-derived RPE cells for cell replacement
      therapies, such as those for AMD. The present study investigated whether RPE
      conditioned medium (RPECM) could promote the differentiation of human adipose
      tissue-derived mesenchymal stromal cells (hADSCs) into RPE cells, and enhance the
      proliferation and migration of these cells. Reverse-transcription quantitative
      polymerase chain reaction analysis demonstrated that RPECM induced hADSCs to
      differentiate into cells expressing RPE markers, including retinoid
      isomerohydrolase (RPE65), cytokeratin (CK8) and Bestrophin, which were identified
      to be significantly upregulated by ~10-fold, 3.5-fold and 2.4-fold, respectively,
      compared with the control group [hADSCs cultured in ADSC-conditioned medium
      (ADSCCM)]. The immunocytochemistry and western blot analysis results demonstrated
      that the protein levels of RPE65, CK8 and Bestrophin were significantly increased
      in RPECM-treated hADSCs. In addition, Cell Counting Kit-8 analysis demonstrated
      that RPECM promoted the proliferation of induced cells. RPECM also increased the
      expression level of the cell proliferative marker Ki-67. Furthermore, to evaluate
      the migration potential, cell migration assays were performed. These assays
      demonstrated that following RPECM treatment hADSCs migrated more quickly compared
      with the control group. The results of the present study suggest that RPECM
      induces hADSCs to differentiate into RPE cells with higher proliferative and
      migratory potentials, which may aid in applications for hADSCs in RPE
      regenerative therapy.

PMID- 29042967
TI  - A case-control study on the treatment of protrusion of lumbar intervertebral disc
      through PELD and MED.
AB  - We compared the clinical effects between the percutaneous endoscopic lumbar
      discectomy (PELD) and microendoscopic discectomy (MED) treatments for protrusion
      of lumbar intervertebral disc. We conducted a retrospective analysis on 60
      patients who were diagnosed with single-segment protrusion of lumbar
      intervertebral disc during the period from January 2009 to June 2016. Patients
      were divided into two groups, the PELD and MED groups, which contained 30 cases
      each. We evaluated the operation results according to oswestry dysfunction index
      (ODI), visual analogue scale (VAS) and the improved MacNab standard. The average
      follow-up visit period after the operation was 18 months and the operation time
      of the two groups was not statistically different. The cadaverine quantity of
      bleeding in the PELD group is less than that in the MED group. Moreover, the
      average length of incision and the length of stay were shortened for the PELD
      group compared to the MED group. The ODI and VAS after operation for the two
      groups improved significantly compared to that before operation (P<0.05). The
      qualified rates of the PELD and MED groups were 93.0 and 90.0%, respectively, as
      of the improved MacNab method. The complication occurrence rates for the two
      groups during perioperative period were not different. Therefore, the short-term
      efficacy of the two minimally invasive operation methods (PELD and MED) on the
      treatment of protrusion of lumbar intervertebral disc is satisfactory. In cases
      where operation indications are chosen strictly, PELD can be regarded as a method
      of safety and efficiency due to the advantages of minimal incision, less
      bleeding, minimal trauma and faster postoperative recovery.

PMID- 29042968
TI  - Hesperetin alleviates renal interstitial fibrosis by inhibiting tubular
      epithelial-mesenchymal transition in vivo and in vitro.
AB  - Hesperetin (HES) is a flavonoid that has been reported to exert protective
      effects against cardiac remodeling, lung fibrosis and hepatic fibrosis. However,
      reports on the effects and potential mechanisms of HES in renal fibrosis are
      limited. In the present study, a unilateral ureteric obstruction (UUO) mouse
      model and a transforming growth factor (TGF)-beta1-activated normal rat kidney
      (NRK)-52E cell model were established. HES was subsequently administered to these
      models to evaluate its anti-fibrotic effects and potential underlying mechanisms
      of action. The results demonstrated that HES reduced obstruction-induced renal
      injury and deposition of the extracellular matrix components collagen-I and
      fibronectin in UUO mouse kidneys (P<0.05). Furthermore, HES treatment
      significantly suppressed EMT, as evidenced by decreased expression of alpha
      smooth muscle actin and E-cadherin, (P<0.05). Additionally, HES inhibited the
      hedgehog signaling pathway in UUO mice and TGF-beta1-treated NRK-52E cells. The
      present findings indicate that HES treatment may inhibit EMT and renal fibrosis
      in vivo and in vitro by antagonizing the hedgehog signaling pathway.

PMID- 29042969
TI  - Silencing of TCTN1 inhibits proliferation, induces cell cycle arrest and
      apoptosis in human thyroid cancer.
AB  - Tectonic family member 1 (TCTN1) is one of the tectonic family members, and a
      regulator of the hedgehog signaling pathway, which has been studied in various
      cancer types, including prostate and pancreatic cancer. However, its function in
      thyroid cancer has not been well documented. Therefore, the present study
      investigated the function of TCTN1 in thyroid cancer using a loss-of-function
      assay. Lentivirus-mediated RNA interference was applied to downregulate TCTN1 in
      the thyroid cancer cell lines, CAL62 and 8305C. A series of functional
      properties, including cell viability, colony formation, cell cycle and apoptosis
      were determined using MTT, colony formation assay and flow cytometry analyses,
      respectively. The results demonstrated that lentivirus-medicated RNAi could
      specifically suppress the expression of TCTN1 at the mRNA and protein levels in
      CAL62, and 8305C cells. Knockdown of TCTN1 inhibited cell growth and
      proliferation via inducing S phase arrest, and apoptosis. Mechanistically, the S
      phase arrest was accompanied by the upregulation of cyclin dependent kinase 2,
      cyclin A2 and downregulation of cyclin B1. Knockdown of TCTN1 induced apoptosis
      through increasing the expression of Bcl2-associated agonist of cell death,
      cleaved caspase-3 and poly(ADP-ribose)polymerase, and decreasing apoptosis
      regulator Bcl-2 expression. The current study highlights the essential role of
      TCTN1 in promoting thyroid cancer cell proliferation, and its knockdown may serve
      as a potential therapeutic treatment for thyroid cancer.

PMID- 29042970
TI  - Effects of 17-DMAG on diffuse large B-cell lymphoma cell apoptosis.
AB  - 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) is a water soluble,
      semisynthetic derivative of endotoxin that has anticancer effects. The aim of the
      present study was to determine whether 17-DMAG enhances the apoptosis of lymphoma
      cells in diffuse large B-cell lymphoma. Apoptosis was induced in SU-DHL-4 diffuse
      large B-cell lymphoma cells treated with 17-DMAG, as evaluated by MTT assay and
      flow cytometry analysis. Apoptosis-associated protein levels were assessed using
      western blotting, and the results indicated that B-cell lymphoma 2 (Bcl-2)
      associated protein X (Bax) was upregulated, whereas heat shock protein family A
      member 5 (HSPA5) and Bcl-2 were downregulated. Additionally, staining with
      5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide revealed that
      treatment with 17-DMAG decreased mitochondrial membrane potential in SU-DHL-4
      diffuse large B-cell lymphoma cells. These results suggested that 17-DMAG is able
      to inhibit proliferation in diffuse large B-cell lymphoma cells in a
      concentration-dependent manner. The underlying mechanism may be that 17-DMAG
      induces oxidative stress, which inhibits the expression of HSPA5 and Bcl-2 and
      promotes the expression of Bax, leading to the apoptosis of SU-DHL-4 cells. Taken
      together, these results indicated that 17-DMAG may be an effective novel agent
      for the treatment of diffuse large B-cell lymphoma.

PMID- 29042971
TI  - Histological evidence of reparative activity in chorioamniotic membrane following
      open fetal surgery for myelomeningocele.
AB  - An increased understanding of the reparative process in fetal membrane following
      surgical techniques may be helpful to decrease the risks to mother and fetus and
      avoid adverse pregnancy outcomes. The present study discusses histological
      evaluation of the fetal membrane following open fetal surgery. Chorioamniotic
      membranes (n=10) were obtained following birth from pregnancies that underwent
      open fetal surgery for myelomeningocele. The collagen distribution was quantified
      using picrosirius-polarization method comparing the suture site with non-suture
      site. The differences between the collagen fiber percentages at the two sites was
      evaluated by the paired t-test with P<0.05. The mean gestational age of fetal
      surgery was 26.09+/-0.3 and 33.81+/-0.82 weeks at birth. The picrosirius red sign
      was more intense at the suture site, primarily associated with collagen type 1.
      Collagen observed in the surgical area was significantly increased (13.22+/
      2.84%) compared with the non-surgical area (6.16+/-1.09%; P<0.0001). It was
      observed that the reparative activity at the suture site of the fetal membrane
      was characterized by a significant increase in collagen fibers. The findings
      suggest nascent collagen synthesis, tissue remodeling and repair of suture site,
      a mechanism likely to prevent the amniotic fluid leakage and maintain pregnancy
      following open fetal surgery.

PMID- 29042972
TI  - Expression and association of VEGF-Notch pathways in infantile hemangiomas.
AB  - The vascular endothelial growth factor (VEGF) and Notch signaling pathways have
      been identified to be involved in the neovascularization, and angiogenesis of
      various tumor types. However, there is little data regarding their roles and
      association in infantile hemangiomas (IHs). In the present study, the
      significance and association of the VEGF-VEGF receptor (R)2, and delta like
      canonical Notch ligand 4 (Dll4)-Notch1 pathways in different clinical phases of
      IHs were investigated. Specimens in the proliferating phase (n=15) and involuting
      phase (n=12) were collected. Quantitative polymerase chain reaction was used to
      analyze the mRNA levels of VEGF, VEGFR2, Dll4 and Notch1. A further 61 paraffin
      embedded IHs (26 in the proliferating group and 35 in the involuting group)
      specimens were collected to investigate the protein levels of Notch1 and Dll4
      using immunohistochemistry, and then analyzed for the association between these
      factors and microvessel density (MVD). The relative expression levels of VEGF,
      VEGFR2 and Dll4 mRNA in the proliferating group were significantly higher
      compared with that in the involuting group. In addition, the relative levels of
      Notch1 mRNA were similar in the proliferating and involuting phases. Expression
      levels of VEGFR2 and Dll4 mRNA were positively correlated with Notch1 expression
      in the proliferating IHs. The relative expression of VEGFR mRNA was positively
      correlated with Dll4 in the proliferating and involuting groups.
      Immunohistochemical staining demonstrated that Notch1 and Dll4 protein were
      upregulated in the proliferating IHs compared with the control group. In the
      proliferating IHs, Notch1 and Dll4 protein expression levels were positively
      correlated with MVD, while in the involuting phase, only Dll4 was positively
      correlated with MVD. The expression levels of related factors in the VEGF and
      Notch pathways, and the associations among them suggest that they may be involved
      in the regulation of IH neovascularization and angiogenesis.

PMID- 29042973
TI  - The efficacy of microsurgery in the treatment of cerebral aneurysm rupture and
      its effect on NF-kappaB, MCP-1 and MMP-9.
AB  - The clinical efficacy of microsurgical neck clipping for the treatment of
      cerebral aneurysm rupture and its effect on serum nuclear factor kappa-light
      chain-enhancer of activated beta cells (NF-kappaB), monocyte chemoattractant
      protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) levels were
      investigated. A total of 56 patients with first occurrence of cerebral aneurysm
      rupture were enrolled from June 2015 to June 2016. These patients were divided
      into control (25 patients) and observation groups (31 patients) according to
      treatment received. The patients in the control group were treated with
      interventional embolization and extraventricular drainage, while the patients in
      the observation group were treated with microsurgical neck clipping. Serum NF
      kappaB, MCP-1 and MMP-9 levels were measured by ELISA prior to the operation and
      at 6 h post-operation. Clinical effects were compared at the 6-month follow-up.
      There was no significant difference in the success rate of the operation between
      the two groups (p>0.05). The incidence of complications in the observation group
      was significantly lower than that in the control group (p<0.05). The Glasgow
      Outcome Scale score was significantly improved in the observation group (p<0.05)
      compared with the control group. Serum NF-kappaB, MMP-9 and MCP-1 were
      significantly decreased in both groups at 6 and 24 h after operation, but the
      observational group showed significantly lower levels for all three proteins than
      the control group (p<0.05). The application of early microsurgical neck clipping
      for the treatment of cerebral aneurysm rupture can reduce complications and
      improve clinical prognosis, and this may be related to a decrease in serum
      inflammatory response-related factors (NF-kappaB and MCP-1) and MMP-9.

PMID- 29042974
TI  - Curative effect of laparoscopic hysterectomy for uterine fibroids and its impact
      on ovarian blood supply.
AB  - This study evaluates the curative effects laparo-scopic hysterectomies performed
      to treat uterine fibroids and determined the impact of the procedures on ovarian
      blood supply. A total of 124 patients with uterine fibroids admitted and treated
      in our hospital from December 2014 to December 2015 participated in the study.
      Two groups of 62 patients each were formed according to different operating
      plans; one group of patients underwent abdominal (open) panhysterectomy and were
      set as the control group; with the other group of patients were treated with
      laparoscopic hysterectomy and were set as the observation group. Ovarian
      endocrine function tests and blood supply changes were measured in both groups
      before the operation and one month after it, and the clinical conditions of all
      the patients were followed up for 24 months after surgery. Our results showed the
      duration of operation, amount of bleeding and time to recovery after the
      procedure were significantly lower in the patients in the observation group
      (P<0.05). Also, compared with preoperative conditions, the levels of PRL, FSH,
      E2, LH and other ovarian function markers in both groups were significantly lower
      one month after the operation, but the levels of the patients in the observation
      group were still significantly higher than those of the patients in the control
      group (P<0.05). Likewise, the surgeries affected the ovarian blood supply in
      patients of both groups, as evidenced by the lower levels of PI, RI, Vmin, Vmax
      and other blood supply indexes observed by Doppler ultrasound a month after the
      operations. However, the impact of the surgery on the ovarian blood supply was
      less marked in the patients in the observation group as their levels remained
      higher than those of patients in the control group (P<0.05). The numbers of
      patients with completely healed abdominal muscular layers in the observation
      group were always significantly higher than those of patients in the control
      group, at every different time point examined (1, 4, 8 and 12 months after
      surgery) (P<0.01). At the end of the 24 months of the follow-up period, the
      recurrence rate of fibroids for patients in the observation group was 4.8%. In
      our hands, the laparoscopic hysterectomy procedure to treat uterine fibroids
      showed the usual advantages over the abdominal open hysterectomy, like small
      trauma, short surgical procedure and rapid postoperative recovery, but it also
      proved to cause a significantly smaller impact on ovarian blood supply and should
      be considered whenever uterus preservation is a priority.

PMID- 29042975
TI  - Comparison of DWIBS/T2 image fusion and PET/CT for the diagnosis of cancer in the
      abdominal cavity.
AB  - Fusion images of diffusion-weighted whole-body imaging with background body
      signal suppression and T2-weighted image (DWIBS/T2) demonstrate a strong signal
      for malignancies, with a high contrast against the surrounding tissues, and
      enable anatomical analysis. In the present study, DWIBS/T2 was compared with 18F
      fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography
      (PET/CT) for diagnosing cancer in the abdomen. Patient records, including imaging
      results of examination conducted between November 2012 and May 2014, were
      analyzed retrospectively. In total, 10 men (age, 73.6+/-9.6 years) and 8 women
      (age, 68.9+/-7.1 years) were enrolled into the current study. Of the enrolled
      patients, 2 were diagnosed with hepatocellular carcinoma, 1 with
      cholangiocellular carcinoma, 1 with liver metastasis, 2 with pancreatic ductal
      adenocarcinoma, 1 with renal cell carcinoma and 1 with malignant lymphoma. Benign
      lesions were also analyzed, including adenomyomatosis of the gallbladder (5
      patients), intraductal papillary mucinous neoplasm (4 patients) and right adrenal
      adenoma (1 case). All the patients with cancer showed positive results on
      DWIBS/T2 images. However, only 7 out of 8 patients were positive with PET/CT. One
      patient with right renal cellular carcinoma was positive with DWIBS/T2, but
      negative with PET/CT. All the patients with benign lesions were negative with
      DWIBS/T2 and PET/CT. In conclusion, DWIBS/T2 was more sensitive in diagnosing
      cancer of organs in the abdominal cavity compared with PET/CT. Furthermore,
      negative results with DWIBS/T2 and PET/CT were useful for the diagnosis of benign
      lesions, such as adenomyomatosis of the gallbladder and intraductal papillary
      mucinous neoplasm.

PMID- 29042976
TI  - Anti-obesity effect of robusta fermented with Leuconostoc mesenteroides in high
      fat diet-induced obese mice.
AB  - Robusta beans cultivated with Monascus ruber (RMR) were successively fermented
      with Leuconostoc mesenteroides (LM) and the antiobesity effects were examined. To
      produce an obese mouse model to investigate the hypolipidemic effects, ICR mice
      were fed the same high-fat diet for 6 weeks. Treatment groups were given 10 or
      20% RMR-LM. Body weight changes in the 20% RMR-LM group were lower compared with
      those in the control group. Visceral adipose tissue weight and adipose size were
      significantly lower in the 20% RMR-LM group compared with those in the control
      group. Significant improvement in glucose tolerance was observed in the 10 and
      20% RMR-LM groups compared with the control group. The 20% RMR-LM group exhibited
      a significant reduction in serum glucose concentration. Hepatic mRNA levels of
      sterol regulatory element-binding protein 1, fas cell surface death receptor, and
      peroxisome proliferator-activated receptor gamma, which are associated with
      lipid, and fatty acid metabolism, in the 20% RMR-LM group were significantly
      lower compared with those in the control group. The results of the present study
      demonstrated that 20% RMR-LM may be used to prevent obesity, and ameliorate
      diabetes and lipid metabolism imbalances.

PMID- 29042977
TI  - Contrast-enhanced ultrasound with a novel nanoparticle contrast agent for
      clinical diagnosis in patients with non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) initiates in the non-small cells of the lung
      and is one of the most common types of human cancer. It is known for its rapid
      growth, easy migration, invasion and reoccurrence, and has the highest incidence
      rate of all types of cancer. Early detection of NSCLC is difficult to achieve and
      this is the primary reason for low survival rates in NSCLC. Contrast-enhanced
      ultrasound is the most common application for evaluating patients diagnosed with
      NSCLC. In the present study, a contrast-enhanced ultrasound combined with
      nanoparticles was performed with the aim of identifying patients with NSCLC at an
      early stage. The present study evaluated the effectiveness of administering a
      nanoparticle contrast agent through respiration in combination with enhanced
      ultrasound at improving image quality compared with traditional ultrasound. This
      maybe a novel method of detecting early-stage tumors in patients. There are
      numerous benefits to conducting diagnoses of NSCLC using contrast-enhanced
      ultrasound. It is a non-invasive imaging modality, induces little pain, has a low
      cost, an extensive range and produces high-resolution images. This means that it
      is safer and more beneficial to use in patients with NSCLC than conventional
      imaging examinations, including X-ray and bronchoscopy. Furthermore, the
      nanoscale microbubble contrast agent containing liposome-encapsulated epidermal
      growth factor receptor was inhaled by nebulization, which may lead to an enhanced
      ultrasound image. The sensitivity of contrast-enhanced ultrasound was
      investigated in mice with early stage NSCLC. The results indicated that
      ultrasound administrated with nanoscale microbubble enhanced sensitivity and
      improved image quality compared with simple ultrasound. Furthermore, enhanced
      ultrasound resulted in a reliable and sensitive assessment of tumor mass in early
      stage tumors. Altogether, contrast-enhanced ultrasound facilitated the efficient
      detection of NSCLC in patients in situ at an early stage. This protocol improved
      the understanding of the pathophysiology of NSCLC and may be applied in the
      detection of early-stage tumors in patients suspected of having cancer.

PMID- 29042978
TI  - Antiplatelet drug ticagrelor delays gastric ulcer healing in rats.
AB  - Adenosine diphosphate P2Y12 receptor antagonist clopidogrel is not sufficiently
      safe for the gastric mucosa in patients with high risk of peptic ulcer, since it
      may impair healing of gastric erosions. However, the safety of the novel P2Y12
      receptor antagonist ticagrelor in the gastric mucosa has not been elucidated to
      date. The present study aimed to examine whether ticagrelor delays gastric ulcer
      healing and to elucidate the involved mechanisms. Gastric kissing ulcers were
      produced in rats by luminal application of acetic acid solution, and ticagrelor
      was administered at dose of 10 or 20 mg/kg/day orally for 7 days. On day 8 after
      ulcer induction, the ulcer size, mucosal epithelial cell proliferation of the
      ulcer margin, expression levels of epidermal growth factor (EGF) and vascular
      endothelial growth factor (VEGF), and signal transduction pathways for cell
      proliferation and angiogenesis were measured and compared between the ticagrelor
      treated and untreated model groups. The results revealed that the ulcer size was
      significantly greater in the ticagrelor-treated group compared with the model
      group, while the mucosal epithelial cell proliferation of the ulcer margin was
      significantly decreased in the ticagrelor-treated group. In addition, ticagrelor
      significantly decreased the ulcer-stimulated expression levels of EGF, VEGF,
      phosphorylated extracellular signal-regulated kinase (ERK), phosphorylated P38
      mitogen-activated protein kinase and nuclear factor-kappaB P65 at the ulcer
      margin (P<0.05). These findings suggested that ticagrelor delayed gastric ulcer
      healing. Furthermore, the possible mechanisms underlying the effect of ticagrelor
      were associated with its functions of attenuating the expression levels of VEGF
      and EGF, as well as suppressing the phosphorylation activation of ERK1/2, P38 and
      nuclear factor-kappaB P65. Finally, the gastric epithelial cell proliferation and
      angiogenesis were also inhibited.

PMID- 29042979
TI  - Mechanism of apoptosis involved in gastric mucosal lesions in Tibetans with high
      altitude polycythemia.
AB  - The Tibetan high plateau is a low-oxygen environment, which may cause the
      pathogenesis of high-altitude polycythemia (HAPC). Gastric mucosal lesions (GML)
      are a common complication of HAPC. The molecular mechanisms involved in HAPC
      induced GML have remained to be fully elucidated and were therefore investigated
      in the present study. Gastric tissues of patients with heavy, HAPC-induced GML
      and healthy controls were assessed by ultrastructural and histopathological
      analysis. In addition, terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick-end labeling and reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) analysis were used to detect
      cell apoptosis in the gastric mucosa tissues. Moreover, the expression of genes
      associated with the phosphoinositide-3 kinase (PI3K) pathway was assessed by RT
      qPCR to investigate the mechanism of cell apoptosis in HAPC-induced GML. The
      results revealed a significant increase in the number of red blood cells, gastric
      vessels and the diameter of gastric mucosal vessels in HAPC-induced GML patients
      compared with those in healthy controls. In addition, more red blood cells were
      distributed in gastric tissue not only at the vascular level but also in the
      tissue space. The number of vacuoles was increased in the gastric mucosal cells.
      Furthermore, a significant increase in apoptosis of the gastric mucosal cells was
      identified. The expression of phosphatase and tensin homolog was significantly
      higher in gastric mucosa from patients with HAPC-induced GML compared with that
      in the healthy controls. All of the pathologic changes suggested that significant
      cell apoptosis occurred in the HAPC-induced GML tissues, which may be associated
      with the PI3K pathway. These findings may provide novel insight for the treatment
      of gastric lesions caused by HAPC in the future.

PMID- 29042980
TI  - Diagnosis and treatment of pulmonary mucormycosis: A case report.
AB  - Pulmonary mucormycosis, a relatively rare pulmonary fungal disease, is difficult
      to diagnose and lacks effective treatment. The present study reports the case of
      a 64-year-old patient who was treated successfully for pulmonary mucormycosis in
      Xuan Wu Hospital. The patient presented with low-grade fever and a productive
      cough that persisted for 1 month with no evident cause, and also suffered from
      diabetes mellitus. Prior antibiotic treatment with levofloxacin had been
      ineffective. Culture of mucus obtained by bronchoscopy resulted in a diagnosis of
      pulmonary mucormycosis. The patient received a cumulative dose of 1,355 mg
      amphotericin B over 2 months and presented a full recovery.

PMID- 29042981
TI  - Sophocarpine against enterovirus 71 in vitro.
AB  - Sophocarpine (SCA) is a bioactive alkaloid present in Sophoraflavescens Ait. The
      present study demonstrated that SCA inhibited enterovirus 71 (EV71) infection in
      Vero cells. The results indicated that the 50% cytotoxicity concentration of SCA
      for Vero cells was 1,346 ug/ml, and the 50% inhibition concentration of SCA
      against EV71 was 350 ug/ml. SCA produced a marked inhibitory effect against EV71
      when the Vero cells were treated with SCA prior to infection with the virus.
      Additionally, SCA was effective against EV71 when the Vero cells were infected
      with EV71 (100xTCID50) that had been treated with SCA for 2 h, and was effective
      when the Vero cells were infected with EV71 (100xTCID50) at 37 degrees C under 5%
      CO2 for 2 h prior to treatment with SCA for 2 h. SCA was demonstrated to inhibit
      the attachment and penetration of EV71 and was more effective at inhibiting
      attachment. The assay additionally verified that SCA suppressed the replication
      of viral genomic RNA and indicated that SCA may inhibit EV71 infection in vitro.

PMID- 29042983
TI  - MicroRNA-17 downregulates expression of the PTEN gene to promote the occurrence
      and development of adenomyosis.
AB  - The aim of the current study was to evaluate the expression of microRNA (miR)-17
      in the endometrial tissues of patients with adenomyosis (AM) and determine its
      biological function in the occurrence and development of the disease. A total of
      45 fresh endometrial tissues of AM patients and 32 normal endometrial tissues
      were collected from healthy controls. The expression of miR-17 was evaluated
      using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The
      miR-17-targeting gene phosphatase and tensin homolog (PTEN) was predicted using
      bioinformatics and its expression was evaluated with RT-qPCR and western blot
      analysis. Endometrial cells were isolated from patients with AM and healthy
      controls. They were cultured in vitro and transfected with antagomiR-17 to
      downregulate miR-17 expression, subsequently cell viability and apoptosis were
      measured using MTT and flow cytometry. The expression of PTEN and cell cycle- and
      apoptosis-related proteins were evaluated using western blot analysis.
      Endometrial cells that stably overexpressed PTEN were screened in vitro by co
      culture with G418. A dual-luciferase reporter assay was conducted to verify
      whether miR-17 was directly bound to PTEN mRNA. The results demonstrated that
      expression of miR-17 was significantly increased in the endometrial tissues of
      patients with AM compared with control patients (P<0.05). PTEN mRNA and protein
      expression were significantly lower in the AM group compared with the control
      group (P<0.05). When the expression of miR-17 in the cells was downregulated, the
      expression of PTEN was significantly increased (P<0.05). In addition, expression
      of Bcl-2 protein was significantly decreased and that of Bax protein
      significantly increased compared with the negative control (both P<0.05). The
      expression of cyclins E1 and D1 were also significantly downregulated (P<0.05).
      When PTEN was overexpressed or miR-17 was downregulated, the viability of
      endometrial cells significantly decreased and cell apoptosis significantly
      increased (all P<0.05). A dual-luciferase reporter assay indicated that miR-17
      could directly bind to the PTEN mRNA 3'-untranslated region to regulate its
      expression. Thus the current study indicates that expression of miR-17 was
      increased in the endometrial tissues of patients with AM and may influence cell
      apoptosis and cyclin expression through the targeted regulation of PTEN. These
      results suggest that miR-17 promotes the occurrence and development of AM.

PMID- 29042982
TI  - Expression of glutathione S-transferase A1, a phase II drug-metabolizing enzyme
      in acute hepatic injury on mice.
AB  - In the present study, three models of acute liver injury in mice were induced via
      the administration of CCl4 (35 mg/kg, 24 h), acetyl-para-aminophenol (APAP; 200
      mg/kg, 12 h) and ethanol (14 ml/kg, 8 h) to study the effect of glutathione S
      transferase A1 (GSTA1) on acute liver injury. The serum levels of alanine
      transaminase, aspartate transaminase and liver homogenate indicators (superoxide
      dismutase, glutathione and glutathione peroxidase) were significantly lower in
      model groups compared with the control group (P<0.01), whereas the liver
      homogenate indicator malondialdehyde was significantly increased (P<0.01). The
      expression of GSTA1 in liver was significantly decreased in the model groups
      compared with the control group (P<0.01). GSTA1 protein content was 3.8, 1.3 and
      2.6 times lower in the CCl4, APAP and ethanol model groups, respectively.
      Furthermore, GSTA1 mRNA expression levels decreased by 4.9, 2.1 and 3.7 times in
      the CCl4, APAP and ethanol model groups, respectively. Among the three models,
      the injury induced by CCl4 was the most marked, followed by ethanol and finally
      APAP. These results suggest that GSTA1 may be released by the liver and serve as
      an antioxidant in the prevention of liver damage.

PMID- 29042984
TI  - Bmi1 and BRG1 drive myocardial repair by regulating cardiac stem cell function in
      acute rheumatic heart disease.
AB  - Rheumatic heart disease (RHD) occurs due to the accumulation of complications
      associated with rheumatic fever, and it results in high morbidity and mortality.
      The majority of cases of RHD are diagnosed in the chronic stages, when treatment
      options are limited. A small reservoir of cardiac stem cells is responsible for
      maintaining cardiac homeostasis and repairing tissue damage. Understanding the
      role of cardiac stem cells and the various proteins responsible for their
      functions in different pathological stages of RHD is an important area of
      investigation. Polycomb complex protein BMI-1 (Bmi1) and transcription activator
      BRG1 (BRG1) are associated with the maintenance of stemness in various types of
      stem cells. The present study investigated the role served by Bmi1 and BRG1 in
      cardiac stem cells during various pathological stages of RHD through
      immunohistochemistry and western blotting. A rat model of RHD was established via
      immunization with the Group A Streptococcus M5 protein. The rat was demonstrated
      to develop acute RHD 2 months after the final immunization, characterized by
      cardiac inflammation and tissue damage. Chronic RHD was identified 4 months after
      the final immunization, revealed by cardiac tissue compression and shrinkage.
      Expression of the cardiac stem cell marker mast/stem cell growth factor receptor
      kit was identified to be elevated during acute RHD, but downregulated in the
      chronic stages of RHD. A similar pattern of expression was revealed for Bmi1 and
      BRG1, indicating that they serve a role in regulating cardiac stem cell
      proliferation during acute RHD. These results suggest that cardiac stem cells
      serve a supportive role in the acute, but not chronic, stages of RHD via
      expression of Bmi1 and BRG1.

PMID- 29042985
TI  - Long noncoding RNA eosinophil granule ontogeny transcript inhibits cell
      proliferation and migration and promotes cell apoptosis in human glioma.
AB  - Glioma is the most common primary brain tumor and represents one of the most
      aggressive and lethal types of human cancer. Recent advances have implicated long
      noncoding RNAs (lncRNAs) as crucial mediators of cancer development and
      progression. The present study aimed to investigate the role of a newly
      discovered lncRNA, termed eosinophil granule ontogeny transcript (EGOT), in the
      aggressive abilities of cells in human glioma. It was initially found that the
      relative transcription level of EGOT in glioma cancerous tissues was
      significantly lower than that in adjacent non-cancerous tissues. EGOT was
      differentially expressed in a series of glioma cell lines, with its lowest level
      in high aggressive U251 and U87 cells. When EGOT was overexpressed by an
      expression plasmid, cell viability was significantly inhibited in U251 and U87
      cells. Furthermore, with EGOT overexpression, the cell cycle was arrested at
      G0/G1 phase and consequently, cell apoptosis was significantly promoted along
      with the activities of caspase-3 and caspase-9. The migration abilities of EGOT
      overexpressed cells were inhibited by 71.4% in U251 cells and by 69.5% in U87
      cells. These data suggest that overexpression of EGOT inhibits cell proliferation
      and migration, and promotes cell apoptosis in glioma. Therefore, EGOT has potent
      anticancer activity and may function as a tumor suppressor in human glioma.

PMID- 29042986
TI  - Sevoflurane exposure in postnatal rats induced long-term cognitive impairment
      through upregulating caspase-3/cleaved-poly (ADP-ribose) polymerase pathway.
AB  - The association of anesthetic exposure in infants or young children with the long
      term impairment of neurologic functions has been reported previously; however,
      the underlying mechanisms remain largely unknown. In order to identify
      dysregulated gene expression underlying long-term cognitive impairment caused by
      sevoflurane exposure at the postnatal stage, the present study initially
      performed behavioral tests on adult Wistar rats, which received 3% sevoflurane at
      postnatal day 7 (P7) for different time course. Subsequently, transcriptome
      profiling of hippocampal tissues from experimental and control rats was
      performed. Significant impairment of the working memory was observed in adult
      rats with sevoflurane exposure for 4-6 h, when compared with the control rats.
      The results indicated that a total of 264 genes were aberrantly expressed (51
      downregulated and 213 upregulated; fold change >2.0; P<0.05; false discovery rate
      <0.05) in the hippocampus of experimental adult rats compared with those from
      control rats. Particularly, the expression of caspase-3 gene (CASP3), encoding
      caspase-3 protein, presented the most significant upregulation, which was further
      validated by quantitative polymerase chain reaction and immunohistochemical
      analysis. Further analysis revealed that CASP3 expression level was negatively
      correlated with the rats' spatial working memory performance, as indicated by the
      Y-maze test. The level of cleaved-poly (ADP-ribose) polymerase (PARP), a
      substrate of caspase-3, was also increased in the hippocampus of experimental
      adult rats. Thus, the present study revealed that upregulation of caspase
      3/cleaved-PARP may be involved in long-term cognitive impairment caused by
      sevoflurane exposure in infants, which may be useful for the clinical prevention
      of cognitive impairment.

PMID- 29042987
TI  - Upregulation of Yes-associated protein and transcriptional co-activator with PDZ
      binding motif influences the behavior of LOVO human colon adenocarcinoma cells.
AB  - The present study aimed to investigate the role of Yes-associated protein (YAP)
      and transcriptional co-activator with PDZ-binding motif (TAZ) in the LOVO human
      colon adenocarcinoma cell line and explore the underlying mechanisms. First, the
      expression levels of YAP and TAZ were detected in LOVO cells using reverse
      transcription quantitative PCR, and the results suggested that YAP and TAZ were
      faintly expressed in LOVO cells. To investigate the exact role of YAP and TAZ in
      LOVO cells, stable YAP- and/or TAZ-overexpressing LOVO cell lines were
      established using YAP and/or TAZ expression plasmids. An MTT assay and flow
      cytometry were used to assess cell proliferation and apoptosis, respectively. The
      results indicated that compared with the control, YAP or TAZ overexpression
      significantly increased the proliferation ability of LOVO cells, while apoptosis
      was significantly decreased. Furthermore, the expression of the tumor-associated
      proteins connective tissue growth factor and cysteine-rich angiogenic inducer 61,
      which have critical roles in facilitating cancer cell proliferation, migration
      and invasion, were found to be upregulated following upregulation of YAP and TAZ.
      In addition, the expression of cell apoptosis-associated protein B-cell lymphoma
      2 (Bcl-2) was significantly increased, while Bcl-2-associated X protein and
      caspase-3 were inhibited by YAP or TAZ overexpression. All of these effects were
      amplified when YAP and TAZ were co-overexpressed. In conclusion, YAP and TAZ
      function as tumor promoters in human colon carcinoma, and upregulation of YAP and
      TAZ influences the behavior of LOVO colon adenocarcinoma cells via regulating
      tumor-associated gene expression.

PMID- 29042988
TI  - Toll-like receptor 2 and dectin-1 function as promising biomarker for Aspergillus
      fumigatus infection.
AB  - In recent years, along with the wide application of organ transplantation and
      immunosuppressive agents, as well as the abuse of broad spectrum antibiotics, the
      incidence of invasive fungal infections has been increasing gradually. The
      present study aimed to identify novel biomarkers in cells infected with
      Aspergillus fumigatus. Human umbilical vein endothelial cells (HUVECs) were
      infected with Aspergillus fumigatus and then harvested at different time-points
      (0, 1, 2, 4 and 6 h). The expression Toll-like receptor 2 (TLR2) and dectin-1
      expression were examined using flow cytometry and western blotting, and
      fluorescence-based microscopy was used to evaluate their distribution. The
      results indicated that TLR2 and dectin-1 protein levels were localized on the
      surface of HUVECs, and that dectin-1 was distributed on HUVEC membranes as
      observed under confocal microscope. Immunofluorescence assay result revealed that
      the optical intensity of dectin-1 in the Aspergillus fumigatus-infected group was
      significantly increased at 0, 1 and 2 h compared with the control group (P<0.05).
      However, the optical intensity of TLR2 in the Aspergillus fumigatus-infected
      group was markedly decreased between 0 and 6 h, as compared with the control
      group (P<0.05). Western blot analysis indicated that dectin-1 expression was
      significantly increased and TLR2 expression was significantly decreased at 0, 1
      and 2 h post infection in the Aspergillus fumigatus-infected group compared with
      the control group. Furthermore, the expression of TLR2 was also negatively
      correlated with the concentration of Aspergillus fumigatus. In conclusion, upon
      infection of cells with Aspergillus fumigatus, TLR2 and dectin-1 expression
      levels were significantly altered. Therefore, TLR2 and dectin-1 levels may
      function as promising biomarkers for the treatment or diagnosis of Aspergillus
      fumigatus infection.

PMID- 29042989
TI  - MicroRNA-22 may promote apoptosis and inhibit the proliferation of hypertrophic
      scar fibroblasts by regulating the mitogen-activated protein kinase
      kinase/extracellular signal-regulated kinase/p21 pathway.
AB  - Hypertrophic scarring (HS) is a common skin disorder that occurs during the wound
      healing process, and the pathogenesis of HS remains unclear. Increasing evidence
      indicated that specific microRNAs (miRs) may be involved in the onset and
      progression of HS. In the present study, the association between miR-22 and HS
      was investigated. Reverse transcription-quantitative polymerase chain reaction
      (RT-qPCR) was performed to examine the expression of miR-22 in 30 HS and matched
      normal skin tissues. In addition, human hypertrophic scar fibroblasts (HSFBs)
      were cultured and transfected with miR-22 mimics, and MTT and Annexin V apoptosis
      assays were performed to investigate the role of miR-22 in the proliferation and
      apoptosis of the human HSFBs. Next, RT-qPCR and western blot assays were
      performed to compare the expression levels of mitogen-activated protein kinase
      kinase (MEK), extracellular signal-regulated kinase (ERK) and p21 in
      untransfected and miR-22 mimic-transfected skin fibroblasts. The results
      identified that miR-22 was significantly downregulated in HS tissues as compared
      with the normal skin. Furthermore, transfection with miR-22 mimics in human HSFBs
      led to inhibited cell proliferation, increased apoptosis, as well as to decreased
      MEK expression and ERK1/2 phosphorylation, and increased expression of p21. In
      conclusion, the present study was the first to prove that aberrant expression of
      miR-22 may serve an important role in the pathogenesis of HS by regulating the
      MEK/ERK/p21 pathway, thus suggesting that miR-22 has the potential to become a
      therapeutic target for the treatment of HS.

PMID- 29042990
TI  - Changes of Treg and Th17 cells as well as cytokines in children with acute
      bronchitis.
AB  - The present study aimed to investigate changes of T-regulatory (Treg) and T
      helper (Th)17 cells as well as cytokines in peripheral blood of children with
      acute bronchitis, and to explore the roles of these cells in the pathogenesis of
      acute bronchitis. A total of 126 children who had presented at Renji Hospital
      (Shanghai, China) with acute bronchitis were selected as the observation group
      and 30 healthy children were selected as the control group. Th17/Tregs in the
      peripheral blood of the children of the observation group and the control group
      was detected by flow cytometry. The levels of cytokines interleukin (IL)-17, IL
      22, IL-10 and transforming growth factor (TGF)-beta in peripheral blood serum
      were detected by ELISA. Compared with those in the control group, Treg cells, the
      Treg/Th17 ratio as well as serum IL-10 and TGF-beta levels were significantly
      decreased in the observation group (P<0.05), while Th17 cells as well as serum
      levels of IL-17 and IL-22 were significantly increased (P<0.05). In conclusion,
      Treg/Th17 and the expression of associated cytokines lost their balance in
      children with acute bronchitis, suggesting that Treg and Th17 cells as well as
      their cytokines may be involved in the pathogenesis of acute bronchitis. It may
      be of certain guiding significance to detect Treg/Th17 and levels of serum
      cytokines in peripheral blood for clinical treatment.

PMID- 29042991
TI  - Nuclear factor-kappaB signaling negatively regulates high glucose-induced
      vascular endothelial cell damage downstream of the extracellular signal-regulated
      kinase/c-Jun N-terminal kinase pathway.
AB  - Diabetes mellitus (DM)-induced high blood sugar severely damages vascular
      endothelial cells (VECs), which are in direct contact with the blood. Diabetic
      complications cause difficulties in skin wound healing and VECs are important for
      this process. Previous studies demonstrated that high blood sugar delayed the
      repair of wounded VECs, but the underlying mechanism has remained elusive. To
      explore the effects of diabetic conditions on VEC damage, cells were incubated in
      a medium with high glucose and then subjected to RNA-sequencing based
      transcriptome analysis. The results revealed that numerous biological processes
      were altered by HG stress, including extracellular matrix-receptor interaction,
      NOD-like receptor signaling and the nuclear factor (NF)-kappaB pathway. HG
      treatment increased the levels of phosphorylated inhibitor of NF-kappaB (IkappaB
      alpha), the key NF-kappaB signaling regulator as well as the transcripts of
      plasminogen activator inhibitor-1 and interleukin-8, two inflammatory response
      markers. Treatment with extracellular signal-regulated kinase (ERK)- and c-Jun N
      terminal kinase (JNK)-specific inhibitors U0126 and sp600125, respectively, led
      to the activation of IkappaB-alpha; however, the inhibitor of IkappaBalpha
      phosphorylation Bay11-7082 did not affect ERK and JNK activity, suggesting that
      ERK/JNK signaling occurs upstream of NF-kappaB in VECs. The present study
      provided useful information regarding the effects of diabetes on VECs, which may
      provide approaches for therapies of diabetes-associated complications in the
      future.

PMID- 29042992
TI  - Timosaponin B-III exhibits antidepressive activity in a mouse model of postpartum
      depression by the regulation of inflammatory cytokines, BNDF signaling and
      synaptic plasticity.
AB  - The aim of this study was to investigate the antidepressive effects of
      timosaponin B-III (TB-III) and the underlying mechanism. A postpartum depression
      (PPD) mouse model was established by the administration of dexamethasone sodium
      phosphate during pregnancy. Mice with PPD were assigned to the following groups:
      Model, fluoxetine and high, medium and low doses of TB-III. Post-parturient mice
      without PPD served as a normal control group. To examine the effect of TB-III,
      mice were treated with TB-III, then forced swimming tests (FSTs) and tail
      suspension tests (TSTs) were performed to evaluate depression. Serum and
      hippocampal cytokines, namely tumor necrosis factor (TNF)-alpha, interleukin (IL)
      1beta, IL-6 and IL-10, were quantified using ELISAs and protein levels of
      hippocampal brain-derived neurotrophic factor (BDNF), glucagon synthase kinase
      (GSK)-3beta, glutamate receptor subunit 1 (GluR1), postsynaptic density protein
      95 (PSD95) and synapsin I were quantified using western blot analysis. Compared
      with those in the control group, immobility time in the FST and TST, serum and
      hippocampal TNF-alpha, IL-1beta and IL-6 levels and hippocampal IL-10 levels were
      increased significantly in the model group (P<0.01). Serum IL-10 levels and
      hippocampal levels of BDNF, GSK-3beta, GluR1, PSD95 and synapsin I decreased
      significantly in the model group compared with the control group (P<0.01).
      Fluoxetine or TB-III (10, 20 or 40 mg/kg) treatment significantly decreased
      immobility times in the FST and TST (P<0.01) and significantly reversed the
      aforementioned alterations in cytokine and protein levels (P<0.01). Thus, TB-III
      exhibited a protective effect against depression in PPD and such effects may have
      been mediated via the regulation of inflammatory cytokines, the BNDF signaling
      pathway and synaptic plasticity-related proteins.

PMID- 29042993
TI  - Sitagliptin ameliorates high glucose-induced cell proliferation and expression of
      the extracellular matrix in glomerular mesangial cells.
AB  - Diabetic nephropathy (DN) is one of the most important causes that leads to end
      stage renal disease and the efficacy of strategies currently available for the
      prevention of DN remains unsatisfactory. Sitagliptin (SIT), which is a dipeptidyl
      peptidase-4 inhibitor, exhibited a modest beneficial effect on glycated
      hemoglobin levels and is capable of ameliorating renal ischemia reperfusion
      injury. By determining the expression of transforming growth factor-beta1 (TGF
      beta1), connective tissue growth factor (CTGF), collagen type IV (ColIV) and
      fibronectin (FN) levels in high glucose-cultured glomerular mesangial cells
      (MCs), the present study aimed to assess the anti-proliferative and anti-fibrotic
      effects of SIT on the therapeutic potential for the prevention of DN and its
      mechanism. Specifically, cell proliferation was determined via cell counting kit
      8 assay, and the expression levels of TGF-beta1 and CTGF mRNA were detected by
      reverse transcription polymerase chain reaction analysis. Furthermore, the
      secretion of TGF-beta1, CTGF, ColIV and FN proteins was measured via enzyme
      linked immunosorbent assays. The results demonstrated that high glucose induced
      the proliferation of MCs and enhanced the expression of TGF-beta1, CTGF, ColIV
      and FN. Furthermore, treatment with SIT inhibited cell proliferation and the
      expression of TGF-beta1, CTGF, ColIV and FN induced by high glucose. In
      conclusion, SIT inhibits cell proliferation and the expression of the major
      extracellular matrix proteins induced by high glucose, indicating its value for
      treating or relieving DN.

PMID- 29042994
TI  - Immunological mechanism of low-dose priming radiation resistance in walker-256
      tumor model mice.
AB  - The aim of the present study was to investigate whether low-dose priming
      radiation induces antitumor immunity that can be augmented by the modulation of
      natural killer (NK) cell and cytokine activity using a mouse tumor model. Walker
      256 cells were injected into the right flank of male BALB/c mice. At 7 days after
      inoculation, mice were divided into three groups, including group 1,2,3. In group
      1 the mice were without radiation, in group 2 the mice were received 2 Gy
      radiation only, and in group 3 the mice were radiated with a priming dose of 75
      mGy followed by 2 Gy radiation after 24 h. On day 21 following the radiation, the
      tumors were removed and the tumor index (tumor weight as a percentage of body
      weight) was calculated. At 1, 7, 14 and 21 days following the 2 Gy radiation,
      mouse splenocytes were isolated to analyze the NK activity and measure the
      production of the cytokines interleukin-1beta, interferon-gamma and tumor
      necrosis factor-alpha by ELISA. Apoptosis was also measured by flow cytometry.
      The results demonstrated that priming radiation significantly delayed the tumor
      growth and prolonged the median survival time to 38 days compared with the 31-day
      survival in the 2 Gy radiation group. The percentage of apoptotic cells was
      significantly higher in the mice that received 75 mGy + 2 Gy radiation compared
      with that in the mice that received 2 Gy alone; by contrast, mice that were not
      irradiated exhibited a relatively low level of apoptosis. The primed mice had a
      higher level of NK activity as compared with the mice exposed to 2 Gy radiation
      only or mice that were not irradiated. Furthermore, cytokine expression remained
      at a higher level in mice receiving priming dose of radiation compared that in
      the mice receiving only 2 Gy radiation. In conclusion, the results indicated that
      low-dose priming X-ray radiation may enhance the NK activity and the levels of
      cytokines, and that the immune response serves an important role in anticancer
      therapy, including radiotherapy.

PMID- 29042995
TI  - Overexpression of dominant-negative Ikaros 6 isoform is associated with
      resistance to TKIs in patients with Philadelphia chromosome positive acute
      lymphoblastic leukemia.
AB  - The clinical significance of the dominant-negative Ikaros 6 (DN-IK6) in the
      treatment of patients with Philadelphia-positive acute lymphoblastic leukemia
      (Ph+-ALL) with tyrosine kinase inhibitors (TKIs) remains elusive. In the present
      study, it was demonstrated that DN-IK6 was overexpressed in B-cell (B)-ALL cases
      compared with T cell-ALL cases at the mRNA and protein levels. Furthermore,
      nucleotide sequencing revealed that DN-IK6 was due to the deletion of IKAROS
      family zinc finger 1 exons 4-7. The outcome of patients with Ph+-B-ALL with DN
      IK6, and treated with TKIs and hyper
      cyclophosphamide/vincristine/doxorubicin/dexamethasone regimen were
      restrospectively evaluated in a 2 year follow-up. The results demonstrated that
      those with the DN isoform exhibited significantly lower incidences of remission,
      shorter median cumulative incidence of relapse times (P<0.05) and shorter median
      overall survival times (P<0.05) compared with those without the DN isoform. In
      conclusion, the results of the present study demonstrated that DN-IK6 is
      overexpressed in the majority of patients with Ph+-ALL, and is significantly
      associated with resistance to TKI therapy.

PMID- 29042996
TI  - IL-32gamma promotes integrin alphavbeta6 expression through the activation of NF
      kappaB in HSCs.
AB  - Hepatic stellate cell (HSC) activation is important in the pathogenesis of liver
      fibrosis. However, the molecular mechanism of HSC activation is not completely
      understood. In the present study, it was demonstrated that interleukin-32gamma
      (IL-32gamma) is capable of enhancing intefgrin alphavbeta6 expression by inducing
      integrin alphavbeta6 promoter activity in a dose-dependent manner in HSCs.
      Furthermore, it was determined that nuclear factor kappaB (NF-kappaB) activation
      is required for IL-32gamma-induced integrin alphavbeta6 expression. Increased
      integrin alphavbeta6 expression is then able to activate HSCs. These results
      indicate that NF-kappaB activation is required for IL-32gamma to induce integrin
      alphavbeta6 expression and consequently promote HSC activation. Therefore, IL
      32gamma activates HSCs and therefore may be associated with hepatic fibrogenesis.
      These results may enable the development of novel effective strategies to treat
      hepatic fibrosis.

PMID- 29042997
TI  - CD19+CD24hiCD38hi regulatory B cells are associated with insulin resistance in
      type I Hashimoto's thyroiditis in Chinese females.
AB  - Hashimoto's thyroiditis (HT) is typically associated with insulin resistance. The
      aim of the present study was to investigate the role of regulatory B cells
      (Bregs) in insulin resistance in patients with HT. A total of 52 female patients
      with type I HT and 35 matched healthy volunteers were enrolled. Demographic and
      laboratorial data were collected. A 75 g oral glucose tolerance test was
      performed on each subject. Flow cytometry was performed to evaluate the levels of
      CD19+CD24hiCD38hi Bregs in peripheral blood. Patients with HT exhibited
      significantly higher postprandial insulin levels (P<0.01), but normal glucose
      levels. The level of CD19+CD24hiCD38hi Bregs in patients with HT decreased
      significantly (P=0.0002) compared with the controls. Pearson's linear correlation
      model revealed a significant, negative association between anti-thyroid
      peroxidase antibodies (TPOAb) and homeostasis model assessment of beta cell (r=
      0.313, P=0.014). The same correlation model revealed a significant, negative
      association between TPOAb and the disposition index (DI; r=-0.305, P=0.017), and
      between anti-thyroglobulin antibodies and DI (r=-0.321, P=0.013). Patients with a
      decreased ratio of CD19+CD24hiCD38hi Bregs to CD19+ lymphocytes exhibited higher
      levels of total cholesterol and low-density lipoprotein cholesterol. A decrease
      in the ratio of CD19+CD24hiCD38hi Bregs to lymphocytes was a significant
      independent risk factor for hyperinsulinemia (odds ratio=1.372, P=0.035). A
      decrease in peripheral blood CD19+CD24hiCD38hi Bregs is associated with insulin
      resistance in HT patients, and was an independent risk factor for postprandial
      hyperinsulinemia. The present study provided a novel insight into the development
      of effective therapeutic strategies targeting immune mechanisms associated with
      HT.

PMID- 29042998
TI  - MicroRNA-206 inhibits the viability and migration of medulloblastoma cells by
      targeting LIM and SH3 protein 1.
AB  - MicroRNA (miR)-206 has been found to be deregulated in various types of human
      cancer, including medulloblastoma. However, the regulatory mechanism of miR-206
      in medulloblastoma growth and metastasis remains largely unclear. In the present
      study, reverse transcription-quantitative polymerase chain reaction data
      indicated that miR-206 was significantly downregulated in medulloblastoma tissues
      compared with adjacent non-tumor tissues (P<0.01). Furthermore, low expression of
      miR-206 was significantly associated with seeding at presentation and anaplastic
      histology (P<0.01), but not with sex, age, or residual tumors. Overexpression of
      miR-206 significantly reduced the viability and migration of medulloblastoma D341
      cells (P<0.01). LIM and SH3 protein 1 (LASP1) was further identified as a novel
      target of miR-206 in D341 cells. mRNA levels of LASP1 were significantly higher
      in medulloblastoma tissues compared to adjacent non-tumor tissues (P<0.01), with
      an inverse correlation to the miR-206 levels in medulloblastoma tissues. In
      addition, protein expression levels of LASP1 ere negatively regulated by miR-206
      in D341 cells. Further investigation showed that overexpression of LASP1
      significantly eliminated the inhibitory effects of miR-206 on the migration and
      invasion of D341 cells (P<0.01). In conclusion, our study demonstrates that miR
      206 has a suppressive role in medulloblastoma cell viability and invasion, partly
      at least, via the targeting of LASP1. Our study highlights the importance of the
      miR-206/LASP1 in medulloblastoma.

PMID- 29042999
TI  - Pien Tze Huang inhibits the proliferation of colorectal cancer cells by
      increasing the expression of miR-34c-5p.
AB  - MicroRNAs (miRNAs) are small, short endogenous non-coding RNA that act as
      oncogenes or tumor suppressors, and serve an important role in various human
      malignant cancers, including colorectal cancer (CRC). Evidence has indicated that
      miRNAs regulate the expression of various genes associated with human cancer, in
      particular the miR-34 family. A well-known traditional Chinese formula, Pien Tze
      Huang (PZH), has a significant clinical effect on CRC. Previous studies have
      demonstrated that PZH inhibits CRC growth in vitro and in vivo via multiple
      mechanisms, including the induction of apoptosis, inhibition of cell
      proliferation and tumor angiogenesis. To further elucidate the molecular
      mechanisms underlying the antitumor activity of PZH, in the present study its
      effects on cell proliferation and miRNA expression in human colon carcinoma (HCT)
      8 cell lines was examined. It was observed that treatment with PZH inhibited cell
      viability and upregulated the expression of miR-34c-5p in HCT-8 cells. In
      addition, transfection with an miR-34c-5p mimic and treatment with PZH inhibited
      cell survival and arrested the cell cycle between the G0/G1 and S phase in HCT-8
      cells. Furthermore, PZH treatment and transfection with miR-34c-5p downregulated
      the expression of cyclin-dependent kinase 4 and cMyc (a promoter of cell
      proliferation), and increased the expression of p53, which is a promoter of
      apoptosis. These results suggest that PZH may suppress proliferation in CRC cells
      by upregulating the expression of miR-34c-5p, which provides a novel perspective
      for understanding the mode of action of PZH.

PMID- 29043000
TI  - Effect of entecavir in the treatment of patients with hepatitis B virus-related
      compensated and decompensated cirrhosis.
AB  - Chronic hepatitis B virus (CHB) infection is a burden on global healthcare and is
      associated with a higher risk of serious sequelae, including cirrhosis and
      hepatocellular carcinoma. The clinical application of entecavir as a treatment
      for CHB has produced positive outcomes, and so is an attractive form of
      pharmacological therapy. However, little data exists comparing the safety and
      efficacy of entecavir for the treatment of hepatitis B virus (HBV)-related
      compensated, and decompensated cirrhosis, respectively. The aim of the present
      study was to evaluate entecavir therapy as a treatment for patients with HBV
      related compensated and decompensated cirrhosis. A retrospective analysis of 46
      compensated patients (compensated group) and 51 decompensated cirrhotic patients
      (decompensated group) treated with entecavir was conducted. Baseline
      demographics, clinical outcomes, and adverse events during the treatment were
      compared. Treatment with entecavir for 96 weeks resulted in significant
      improvements in serum levels of HBV DNA (P=0.002), albumin (P=0.014),
      cholinesterase (CHE; P=0.001), HBV DNA negativity rate (P=0.004), Child-Turcotte
      Pugh score (P=0.030), alanine aminotransferase normalized rate (P=0.039), and the
      degree of esophageal varices liver stiffness (P=0.002) in the two groups.
      However, statistical analysis revealed that the improvements were significantly
      higher in the compensated group compared with the decompensated group (P<0.05).
      The complement component (C)3 and C4 levels were also significantly increased in
      the compensated group compared with the decompensated group at weeks 24, 48 and
      96 (P<0.05). In addition, the incidences of hepatocellular carcinoma, upper
      digestive tract hemorrhage and ascites were significantly higher in the
      decompensated group compared with the compensated group (P<0.05). In conclusion,
      treatment with 96-week entecavir therapy produced similar clinical outcomes in
      compensated and decompensated cirrhotic patients via inhibiting HBV-DNA viral
      load and recovering complement C3 and C4; however, entecavir exerts a better
      effect on patients with compensated cirrhosis, and so this therapy may improve
      the prognosis of such patients.

PMID- 29043001
TI  - Effect of Pingchuan Guben decoction on patients with chronic obstructive
      pulmonary disease: Results from a randomized comparative effectiveness research
      trial.
AB  - Chronic obstructive pulmonary disease (COPD) is known to be a systemic low-grade
      ongoing inflammation exerting major health and economic burden worldwide.
      Complementary and alternative medicines, such as Traditional Chinese Medicine,
      are widely used for the treatment of patients with COPD. The present study was
      designed to investigate the efficacy of Pingchuan Guben decoction on patients
      with COPD through a double-blinded, open-labeled, randomized controlled trial. A
      total of 86 patients were randomly assigned to two groups, with 43 patients in
      the intervention group and 43 cases in the control group. The patients in the
      control group were treated with conventional western medicine, and the
      intervention group received a combination of conventional western medicine and
      Pingchuan Guben decoction. After 12 weeks of treatment, the mean 6-minute walking
      distance, forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC)
      and FEV1/FVC in the intervention group were significantly higher than those of
      the control group (P<0.05). The levels of inflammation factors and protease
      molecules were significantly ameliorated in the intervention group compared with
      the control group (P<0.05). The levels of Kelch-like ECH-associated protein 1
      (Keap1), nuclear factor-E2-related factor-2 (Nrf2), superoxide anions,
      malondialdehyde, glutathione S-transferase and glutathione peroxidase were
      significantly more improved in the intervention group compared with those in the
      control group over the 12-week study period (P<0.05). Therefore, combinations of
      western medicine with Pingchuan Guben decoction may exert therapeutic effects on
      patients with COPD via modulations of inflammation factors and protease
      molecules, as well as the activation of the Keap1/Nrf2 signaling pathway.

PMID- 29043002
TI  - Humanin analogue, S14G-humanin, has neuroprotective effects against oxygen
      glucose deprivation/reoxygenation by reactivating Jak2/Stat3 signaling through
      the PI3K/AKT pathway.
AB  - Stroke, characterized by a disruption of blood supply to the brain, is a major
      cause of morbidity and mortality worldwide. Although humanin, a 24-amino acid
      polypeptide, has been identified to have multiple neuroprotective functions, the
      level of humanin in plasma has been demonstrated to decrease with age, which
      likely limits the effects against stroke injury. A potent humanin analogue, S14G
      humanin (HNG), generated by replacement of Ser14 with glycine, has been
      demonstrated to have 1,000-fold stronger biological activity than humanin. The
      present study established an in vitro oxygen glucose deprivation/reoxygenation
      (OGD/R) model using SH-SY5Y neuroblastoma cells to mimic the in vivo
      ischemia/reperfusion injury in stroke. Adding HNG (0-10 ug/l) to SH-SY5Y cells to
      different extents blocked OGD/R-induced reduction of cell viability and
      antioxidative capacity, as well as decreased the elevated apoptosis rate induced
      by OGD/R, with the most evident effects at 1 ug/l HNG. Janus kinase 2
      (Jak2)/signal transducer and activator of transcription 3 (Stat3) signaling was
      attenuated in OGD/R processes, yet reactivated with HNG treatment. FLLL32 (5 uM),
      a specific inhibitor of the signal, abolished effects of HNG on anti-apoptosis
      and antioxidation in OGD/R processes. Co-treatment with HNG and FLLL32 failed to
      interrupt upregulation of cytochrome c, B-cell lymphoma 2-associated X protein
      and cleaved caspase-3 provoked by OGD/R. Similar to FLLL32, Jak2/Stat3 signaling
      activated by HNG was also repressed by inhibitor of phosphoinositide 3-kinase
      (PI3K; 10 uM LY294002) or protein kinase B (AKT; 5 uM MK-2206 2HCl). These data
      collectively indicated that HNG has neuroprotective effects against OGD/R by
      reactivating Jak2/Stat3 signaling through the PI3K/AKT pathway, suggesting that
      HNG may be a promising agent in the management of stroke.

PMID- 29043003
TI  - Tiaogeng Yijing decoction improves the pregnancy outcomes of patients with poor
      ovarian response undergoing in vitro fertilization-embryo transfer.
AB  - The present study aimed to explore the therapeutic effects of the Tiaogeng Yijing
      decoction on patients with poor ovarian response (POR) undergoing in vitro
      fertilization-embryo transfer (IVF-ET), in addition to the underlying molecular
      mechanisms of these effects. A total of 40 patients were randomly and equally
      assigned to the treatment or control group. Patients in the treatment group
      received the Tiaogeng Yijing decoction continuously for three menstrual cycles in
      addition to microstimulation, while patients in the control group underwent
      microstimulation only. The following molecules were measured following treatment:
      Serum levels of sex hormones, including follicle-stimulating hormone (FSH),
      luteinizing hormone (LH), estradiol (E2) and anti-mullerian hormone (AMH);
      follicular fluid levels of cytokines, including growth differentiation factor
      (GDF)-9, transforming growth factor (TGF)-beta1, leukemia inhibitory factor
      (LIF), granulocyte-colony stimulating factor (G-CSF) and vascular endothelial
      growth factor (VEGF); and endometrial levels of cytokines, including integrin
      alphaVbeta3, TGF-beta1, LIF, G-CSF and VEGF. In addition, the antral follicle
      count (AFC), mean ovarian diameter (MOD) and pregnancy outcomes were measured.
      The results revealed that the Tiaogeng Yijing decoction significantly decreased
      serum levels of FSH and E2, and significantly increased serum AMH levels, the
      AFC, follicular fluid levels of GDF-9, TGF-beta1 and VEGF, and endometrial levels
      of integrin alphaVbeta3, TGF-beta1 and VEGF, in addition to pregnancy outcomes
      (all P<0.05 vs. the control group). However, no significant differences were
      found in the MOD or levels of LH, LIF and G-CSF. In conclusion, the present study
      demonstrated that the Tiaogeng Yijing decoction promotes pregnancy outcomes in
      patients with POR undergoing IVF-ET, and that this effect may be associated with
      the upregulation of TGF-beta1 and VEGF in the follicular fluid and endometrium.

PMID- 29043004
TI  - Efficacy of perineural dexamethasone with ropivacaine in adductor canal block for
      post-operative analgesia in patients undergoing total knee arthroplasty: A
      randomized controlled trial.
AB  - Adductor canal block (ACB) is an effective analgesic alternative to femoral nerve
      block after total knee arthroplasty (TKA). The aim of the present study was to
      investigate whether addition of dexamethasone to ropivacaine for ACB is able to
      prolong analgesia and reduce pain. Study participants were randomized into groups
      receiving ACB with either 0.5% ropivacaine + normal saline (control group; n=93)
      or 0.5% ropivacaine + 8 mg dexamethasone (dexamethasone group; n=93). All
      patients were subjected to identical peri-operative management. Patients were
      assessed for the duration of analgesia by the return of pinprick sensation. A
      numerical rating scale, ranging from 0 to 10, was used to assess post-operative
      pain at 6, 12, 18, 24 and 48 h. Opioid use was recorded. Serum C-reactive protein
      and interleukin-6 levels were measured at 3, 6, 12, 24 and 48 h after surgery.
      The results revealed that the duration of sensory block was significantly longer
      in the dexamethasone group (23.42+/-3.35 vs. 14.67+/-2.96 h in control group,
      P<0.05). The dexamethasone group also had significantly lower pain scores at 6,
      12, 18 and 24 h after surgery (all P<0.001), and at 48 h, pain was comparable in
      the two groups. Reduction in post-operative pain was associated with a decrease
      in serum C-reactive protein. Morphine use in the first 24 h after surgery was
      also lower in the dexamethasone group (4.23+/-1.80 vs. 8.42+/-2.44 mg in control
      group, P<0.05). In conclusion, addition of dexamethasone to ropivacaine for ACB
      was able to prolong the duration of analgesia and decreased early post-operative
      pain following TKA.

PMID- 29043005
TI  - Impact of supplementation with a food-derived microbial community on obesity
      associated inflammation and gut microbiota composition.
AB  - BACKGROUND: Obesity is a complex pathology associated with dysbiosis, metabolic
      alterations, and low-grade chronic inflammation promoted by immune cells,
      infiltrating and populating the adipose tissue. Probiotic supplementation was
      suggested to be capable of counteracting obesity-associated immune and microbial
      alterations, based on its proven immunomodulatory activity and positive effect on
      gut microbial balance. Traditional fermented foods represent a natural source of
      live microbes, including environmental strains with probiotic features, which
      could transiently colonise the gut. The aim of our work was to evaluate the
      impact of supplementation with a complex foodborne bacterial consortium on
      obesity-associated inflammation and gut microbiota composition in a mouse model.
      METHODS: C57BL/6J mice fed a 45% high fat diet (HFD) for 90 days were
      supplemented with a mixture of foodborne lactic acid bacteria derived from the
      traditional fermented dairy product "Mozzarella di Bufala Campana" (MBC) or with
      the commercial probiotic GG strain of Lactobacillus rhamnosus (LGG). Inflammation
      was assessed in epididymal white adipose tissue (WAT) following HFD. Faecal
      microbiota composition was studied by next-generation sequencing. RESULTS:
      Significant reduction of epididymal WAT weight was observed in MBC-treated, as
      compared to LGG and control, animals. Serum metabolic profiling showed
      correspondingly reduced levels of triglycerides and higher levels of HDL
      cholesterol, as well as a trend toward reduction of LDL-cholesterol levels.
      Analysis of the principal leucocyte subpopulations in epididymal WAT revealed
      increased regulatory T cells and CD4+ cells in MBC microbiota-supplemented mice,
      as well as decreased macrophage and CD8+ cell numbers, suggesting anti
      inflammatory effects. These results were associated with lower levels of pro
      inflammatory cytokines and chemokines in WAT explants. Faecal bacterial profiling
      demonstrated increased Firmicutes/Bacteroidetes ratio in all mice groups
      following HFD. CONCLUSIONS: Taken together, these results indicate a protective
      effect of MBC microbiota supplementation toward HFD-induced fat accumulation and
      triglyceride and cholesterol levels, as well as inflammation, suggesting a
      stronger effect of a mixed microbial consortium vs single-strain probiotic
      supplementation. The immunomodulatory activity exerted by the MBC microbiota
      could be due to synergistic interactions within the microbial consortium,
      highlighting the important role of dietary microbes with yet uncharacterised
      probiotic effect.

PMID- 29043006
TI  - Does dietary fat affect inflammatory markers in overweight and obese individuals?
      a review of randomized controlled trials from 2010 to 2016.
AB  - BACKGROUND: Obesity, a major cause of death and disability, is increasing
      worldwide. Obesity is characterized by a chronic, low-grade inflammatory state
      which is suggested to play a critical role in the development of obesity-related
      diseases like cardiovascular diseases and type 2 diabetes. In fact, in the hours
      following consumption of a meal, a transient increase in inflammatory markers
      occurs, a response that is exaggerated in obese subjects. Dietary composition,
      including content of dietary fatty acids, may affect this inflammatory response
      both acutely and chronically, and thereby be predictive of progression of
      disease. The aim of the review was to summarize the literature from 2010 to 2016
      regarding the effects of dietary fat intake on levels of inflammatory markers in
      overweight and obesity in human randomized controlled trials. METHODS AND
      RESULTS: We performed a literature search in MEDLINE, EMBASE, and PubMed
      databases. The literature search included human randomized controlled trials,
      both postprandial and long-term interventions, from January 2010 to September
      2016. In total, 37 articles were included. Interventions with dairy products,
      vegetable oils, or nuts showed minor effects on inflammatory markers. The most
      consistent inflammatory-mediating effects were found in intervention with whole
      diets, which suggests that many components of the diet reduce inflammation
      synergistically. Furthermore, interventions with weight reduction and different
      fatty acids did not clearly show beneficial effects on inflammatory markers.
      CONCLUSION: Most interventions showed either no or minor effects of dietary fat
      intake on inflammatory markers in overweight and obese subjects. To progress our
      understanding on how diet and dietary components affect our health, mechanistic
      studies are required. Hence, future studies should include whole diets and
      characterization of obese phenotypes at a molecular level, including omics data
      and gut microbiota.

PMID- 29043008
TI  - Ancestors' dietary patterns and environments could drive positive selection in
      genes involved in micronutrient metabolism-the case of cofactor transporters.
AB  - BACKGROUND: During evolution, humans colonized different ecological niches and
      adopted a variety of subsistence strategies that gave rise to diverse selective
      pressures acting across the genome. Environmentally induced selection of vitamin,
      mineral, or other cofactor transporters could influence micronutrient-requiring
      molecular reactions and contribute to inter-individual variability in response to
      foods and nutritional interventions. METHODS: A comprehensive list of genes
      coding for transporters of cofactors or their precursors was built using data
      mining procedures from the HGDP dataset and then explored to detect evidence of
      positive genetic selection. This dataset was chosen since it comprises several
      genetically diverse worldwide populations whom ancestries have evolved in
      different environments and thus lived following various nutritional habits and
      lifestyles. RESULTS: We identified 312 cofactor transporter (CT) genes involved
      in between-cell or sub-cellular compartment distribution of 28 cofactors derived
      from dietary intake. Twenty-four SNPs distributed across 14 CT genes separated
      populations into continental and intra-continental groups such as African hunter
      gatherers and farmers, and between Native American sub-populations. Notably, four
      SNPs were located in SLC24A3 with one being a known eQTL of the NCKX3 protein.
      CONCLUSIONS: These findings could support the importance of considering
      individual's genetic makeup along with their metabolic profile when tailoring
      personalized dietary interventions for optimizing health.

PMID- 29043009
TI  - Electrochemical Oxidation of Hydrogen in Bis(trifluoromethylsulfonyl)imide Ionic
      Liquids under Anaerobic and Aerobic Conditions.
AB  - The electrochemical behavior of hydrogen oxidation on a platinum electrode in two
      aprotic room temperature ionic liquids (RTILs)-1-butyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide [Bmim][NTf2] and 1-butyl-1-methyl-pyrrolidinium
      bis(trifluoromethylsulfonyl)imide [Bmpy][NTf2]-was investigated in both anaerobic
      and aerobic conditions. At platinum electrode in the ILs, the first step of
      hydrogen oxidation is the formation of Pt-H(ad) (the Tafel step), which is
      similar to those observed in the aqueous electrolytes. However, there are
      differences in the oxidation steps (the Heyrovsky and Volmer steps). In ILs, the
      oxidation of Pt-H(ad) forms a hydrogen radical and a proton rather than a proton
      or a water in aqueous acid or alkaline electrolytes, respectively. This
      difference is significant as it results in a completely different following
      reaction pathway in the anaerobic vs aerobic conditions. A coupled chemical
      reaction between oxygen and hydrogen oxidation intermediates was observed in
      aerobic conditions which has a correlation with hydrogen concentrations.
      Furthermore, the overall rate of hydrogen oxidation is shown to be much higher in
      [Bmpy][NTf2] than that of [Bmim][NTf2], which is rationalized as the result of
      both higher solubility of hydrogen and the unique IL-electrode interface
      structure which promotes the hydrogen adsorption in [Bmpy][NTf2] than that of
      [Bmim][NTf2]. This study is the first example showing that hydrogen oxidation
      mechanism in aprotic ILs follows two different oxidation mechanisms in anaerobic
      and aerobic conditions.

PMID- 29043010
TI  - Primary Cutaneous Mucinous Carcinoma of the Eyelid.

PMID- 29043007
TI  - Amino acid supplements and metabolic health: a potential interplay between
      intestinal microbiota and systems control.
AB  - Dietary supplementation of essential amino acids (EAAs) has been shown to promote
      healthspan. EAAs regulate, in fact, glucose and lipid metabolism and energy
      balance, increase mitochondrial biogenesis, and maintain immune homeostasis.
      Basic science and epidemiological results indicate that dietary macronutrient
      composition affects healthspan through multiple and integrated mechanisms, and
      their effects are closely related to the metabolic status to which they act. In
      particular, EAA supplementation can trigger different and even opposite effects
      depending on the catabolic and anabolic states of the organisms. Among others,
      gut-associated microbial communities (referred to as gut microbiota) emerged as a
      major regulator of the host metabolism. Diet and host health influence gut
      microbiota, and composition of gut microbiota, in turn, controls many aspects of
      host health, including nutrient metabolism, resistance to infection, and immune
      signals. Altered communication between the innate immune system and the gut
      microbiota might contribute to complex diseases. Furthermore, gut microbiota and
      its impact to host health change largely during different life phases such as
      lactation, weaning, and aging. Here we will review the accumulating body of
      knowledge on the impact of dietary EAA supplementation on the host metabolic
      health and healthspan from a holistic perspective. Moreover, we will focus on the
      current efforts to establish causal relationships among dietary EAAs, gut
      microbiota, and health during human development.

PMID- 29043011
TI  - Debates in Allergy Medicine: Allergy skin testing cannot be replaced by molecular
      diagnosis in the near future.
AB  - : Percutaneous skin prick tests (SPT) have been considered the preferred method
      for confirming IgE-mediated sensitization. This reliable and minimally invasive
      technique correlates with in vivo challenges, has good reproducibility, is easily
      quantified, and allows analyzing multiple allergens simultaneously. Potent
      extracts and a proficient tester improve its accuracy. Molecular-based allergy
      diagnostics (MA-Dx) quantifies allergenic components obtained either from
      purification of natural sources or recombinant technology to identify the
      patient's reactivity to those specific allergenic protein components. For a
      correct allergy diagnosis, the patient selection is crucial. MA-Dx has been shown
      to have a high specificity, however, as MA-Dx testing can be ordered by any
      physician, the pre-selection of patients might not always be optimal, reducing
      test specificity. Also, MA-Dx is less sensitive than in vitro testing with the
      whole allergen or SPT. Secondly, no allergen-specific immunotherapy (AIT) trial
      has yet shown efficacy with patients selected on the basis of their MA-Dx
      results. Thirdly, why would we need molecular diagnosis, as no molecular
      treatment can yet be offered? Then there are the practical arguments of costs
      (SPT highly cost-efficient), test availability for MA-Dx still lacking in wide
      areas of the world and scarce in others. As such, it is hard physicians can build
      confidence in the test and their interpretation of the MA-Dx results. IN
      CONCLUSION: as of now these techniques should be reserved for situations of
      complex allergies and polysensitization; in the future MA-Dx might help to reduce
      the number of allergens for AIT, but trials are needed to prove this concept.

PMID- 29043012
TI  - Checklist for a complete chronic urticaria medical history: an easy tool.
AB  - BACKGROUND: Existing guidelines do not offer a quick, efficient alternative to
      the patient's recollection of relevant clinical features during anamnesis and
      physical examination for chronic urticaria (CU). This study aimed to identify
      specific items reflecting the main characteristics of CU that should be included
      in a comprehensive medical history for patients with CU. We also aimed to clarify
      possible eliciting factors for CU to support accurate diagnosis of the disease.
      METHODS: A panel of postgraduate dermatologists conducted a literature search for
      relevant studies on CU using Medline, the Cochrane database, and PubMed. RESULTS:
      We identified82 articles from which we drew a collection of items to inform
      development of an easy-to-use checklist and collection of items that should be
      included in a correct medical history. The final version of the checklist
      included42 items across two areas: essential clues for anamnesis and diagnosis of
      CU; and typical symptoms/parameters or characteristics according to subtype,
      etiology, and laboratory findings. Items included time of disease onset;
      duration, shape, size, color, and distribution of wheals; associated angioedema;
      atopy; and triggering factors. CONCLUSIONS: Our guide provides an easy-to-use
      tool to support clinicians to focus, orient themselves, and save time in medical
      consultations for CU, allowing better diagnosis and management of this disease.

PMID- 29043013
TI  - miR-125a suppresses viability and glycolysis and induces apoptosis by targeting
      Hexokinase 2 in laryngeal squamous cell carcinoma.
AB  - BACKGROUND: miR-125a usually functions as a tumor suppressor in cancers. However,
      the role of miR-125a in laryngeal squamous cell carcinoma (LSCC) has not been
      determined. METHODS: qRT-PCR was applied to measure the expression of miR-125a
      and HK2 mRNA in LSCC tissues and cells. CCK-8 kit and flow cytometry analysis
      were performed to detect cell viability and apoptosis. Luciferase reporter assay
      and RNA immunoprecipitation (RIP) were conducted to confirm the relationship
      between miR-125a and HK2. Commercial test kits were used to determine the
      concentrations of glucose and l-lactate. Xenograft in mice was constructed to
      validate the function and mechanism of miR-125a in LSCC tumor growth. RESULTS: A
      negative correlation was found between miR-125a expression and the level of
      Hexokinase 2 (HK2) mRNA in LSCC tissues. Functional experiments found that miR
      125a inhibited viability and glycolysis and induced apoptosis in LSCC cells.
      Similarly, HK2 downregulation led to viability and glycolysis inhibition and
      induction of apoptosis in LSCC cells in vitro. Moreover, miR-125a overexpression
      suppressed LSCC xenograft growth in vivo. Mechanically, HK2 was verified to be a
      target of miR-125a by luciferase reporter assays and RNA immunoprecipitation
      (RIP) assays. Furthermore, restored HK2 expression reversed miR-125a-mediated
      proliferation and glycolysis inhibition and induction of apoptosis in LSCC cells.
      CONCLUSIONS: miR-125a suppressed LSCC progression by targeting HK2 in vitro and
      in vivo, suggesting that miR-125a may be a potential molecular target for LSCC
      treatment.

PMID- 29043014
TI  - An open-label study to evaluate the long-term safety and efficacy of lanadelumab
      for prevention of attacks in hereditary angioedema: design of the HELP study
      extension.
AB  - BACKGROUND: Hereditary angioedema (HAE) is characterized by recurrent attacks of
      subcutaneous or submucosal edema. Attacks are unpredictable, debilitating, and
      have a significant impact on quality of life. Patients may be prescribed
      prophylactic therapy to prevent angioedema attacks. Current prophylactic
      treatments may be difficult to administer (i.e., intravenously), require frequent
      administrations or are not well tolerated, and breakthrough attacks may still
      occur frequently. Lanadelumab is a subcutaneously-administered monoclonal
      antibody inhibitor of plasma kallikrein in clinical development for prophylaxis
      of hereditary angioedema attacks. A Phase 1b study supported its efficacy in
      preventing attacks. A Phase 3, randomized, double-blind, placebo-controlled,
      parallel-arm study has been completed and an open-label extension is currently
      ongoing. METHODS/DESIGN: The primary objective of the open-label extension is to
      evaluate the long-term safety of repeated subcutaneous administrations of
      lanadelumab in patients with type I/II HAE. Secondary objectives include
      evaluation of efficacy and time to first angioedema attack to determine outer
      bounds of the dosing interval. The study will also evaluate immunogenicity,
      pharmacokinetics/pharmacodynamics, quality of life, characteristics of
      breakthrough attacks, ease of self-administration, and safety/efficacy in
      patients who switch to lanadelumab from another prophylactic therapy. The open
      label extension will enroll patients who completed the double-blind study
      ("rollover patients") and those who did not participate in the double-blind study
      ("non-rollover patients"), which includes patients who may or may not be
      currently using another prophylactic therapy. Rollover patients will receive a
      single 300 mg dose of lanadelumab on Day 0 and the second dose after the
      patient's first confirmed angioedema attack. Thereafter, lanadelumab will be
      administered every 2 weeks. Non-rollover patients will receive 300 mg lanadelumab
      every 2 weeks regardless of the first attack. All patients will receive their
      last dose on Day 350 (maximum of 26 doses), and will then undergo a 4-week follow
      up. DISCUSSION: Prevention of attacks can reduce the burden of illness associated
      with HAE. Prophylactic therapy requires extended, repeated dosing and the results
      of this study will provide important data on the long-term safety and efficacy of
      lanadelumab, a monoclonal antibody inhibitor of plasma kallikrein for
      subcutaneous administration for the treatment of HAE. Trial registration
      NCT02741596.

PMID- 29043015
TI  - "Show me which parasites you carry and I will tell you what you eat", or how to
      infer the trophic behavior of hematophagous arthropods feeding on wildlife.
AB  - Most emerging infectious diseases are zoonoses originating from wildlife among
      which vector-borne diseases constitute a major risk for global human health.
      Understanding the transmission routes of mosquito-borne pathogens in wildlife
      crucially depends on recording mosquito blood-feeding patterns. During an
      extensive longitudinal survey to study sylvatic anophelines in two wildlife
      reserves in Gabon, we collected 2,415 mosquitoes of which only 0.3% were blood
      fed. The molecular analysis of the blood meals contained in guts indicated that
      all the engorged mosquitoes fed on wild ungulates. This direct approach gave only
      limited insights into the trophic behavior of the captured mosquitoes. Therefore,
      we developed a complementary indirect approach that exploits the occurrence of
      natural infections by host-specific haemosporidian parasites to infer Anopheles
      trophic behavior. This method showed that 74 infected individuals carried
      parasites of great apes (58%), ungulates (30%), rodents (11%) and bats (1%).
      Accordingly, on the basis of haemosporidian host specificity, we could infer
      different feeding patterns. Some mosquito species had a restricted host range
      (An. nili only fed on rodents, whereas An. carnevalei, An. coustani, An.
      obscurus, and An. paludis only fed on wild ungulates). Other species had a wider
      host range (An. gabonensis could feed on rodents and wild ungulates, whereas An.
      moucheti and An. vinckei bit rodents, wild ungulates and great apes). An.
      marshallii was the species with the largest host range (rodents, wild ungulates,
      great apes, and bats). The indirect method substantially increased the
      information that could be extracted from the sample by providing details about
      host-feeding patterns of all the mosquito species collected (both fed and unfed).
      Molecular sequences of hematophagous arthropods and their parasites will be
      increasingly available in the future; exploitation of such data with the approach
      we propose here should provide key insights into the feeding patterns of vectors
      and the ecology of vector-borne diseases.

PMID- 29043016
TI  - Population structure of a widespread bat (Tadarida brasiliensis) in an island
      system.
AB  - Dispersal is a driving factor in the creation and maintenance of biodiversity,
      yet little is known about the effects of habitat variation and geography on
      dispersal and population connectivity in most mammalian groups. Bats of the
      family Molossidae are fast-flying mammals thought to have potentially high
      dispersal ability, and recent studies have indicated gene flow across hundreds of
      kilometers in continental North American populations of the Brazilian free-tailed
      bat, Tadarida brasiliensis. We examined the population genetics, phylogeography,
      and morphology of this species in Florida and across islands of The Bahamas,
      which are part of an island archipelago in the West Indies. Previous studies
      indicate that bats in the family Phyllostomidae, which are possibly less mobile
      than members of the family Molossidae, exhibit population structuring across The
      Bahamas. We hypothesized that T. brasiliensis would show high population
      connectivity throughout the islands and that T. brasiliensis would show higher
      connectivity than two species of phyllostomid bats that have been previously
      examined in The Bahamas. Contrary to our predictions, T. brasiliensis shows high
      population structure between two groups of islands in The Bahamas, similar to the
      structure exhibited by one species of phyllostomid bat. Phylogenetic and
      morphological analyses suggest that this structure may be the result of ancient
      divergence between two populations of T. brasiliensis that subsequently came into
      contact in The Bahamas. Our findings additionally suggest that there may be
      cryptic species within T. brasiliensis in The Bahamas and the West Indies more
      broadly.

PMID- 29043017
TI  - Phenotypic selection on flowering phenology and pollination efficiency traits
      between Primula populations with different pollinator assemblages.
AB  - Floral traits have largely been attributed to phenotypic selection in plant
      pollinator interactions. However, the strength of this link has rarely been
      ascertained with real pollinators. We conducted pollinator observations and
      estimated selection through female fitness on flowering phenology and floral
      traits between two Primula secundiflora populations. We quantified pollinator
      mediated selection by subtracting estimates of selection gradients of plants
      receiving supplemental hand pollination from those of plants receiving open
      pollination. There was net directional selection for an earlier flowering start
      date at populations where the dominant pollinators were syrphid flies, and
      flowering phenology was also subjected to stabilized quadratic selection.
      However, a later flowering start date was significantly selected at populations
      where the dominant pollinators were legitimate (normal pollination through the
      corolla tube entrance) and illegitimate bumblebees (abnormal pollination through
      nectar robbing hole which located at the corolla tube), and flowering phenology
      was subjected to disruptive quadratic selection. Wider corolla tube entrance
      diameter was selected at both populations. Furthermore, the strength of net
      directional selection on flowering start date and corolla tube entrance diameter
      was stronger at the population where the dominant pollinators were syrphid flies.
      Pollinator-mediated selection explained most of the between-population variations
      in the net directional selection on flowering phenology and corolla tube entrance
      diameter. Our results suggested the important influence of pollinator-mediated
      selection on floral evolution. Variations in pollinator assemblages not only
      resulted in variation in the direction of selection but also the strength of
      selection on floral traits.

PMID- 29043018
TI  - Invasive cane toads are unique in shape but overlap in ecological niche compared
      to Australian native frogs.
AB  - Invasive species are an important issue worldwide but predicting invasiveness,
      and the underlying mechanisms that cause it, is difficult. There are several
      primary hypotheses to explain invasion success. Two main hypothesis based on
      niche spaces stand out as alternative, although not exclusive. The empty niche
      hypothesis states that invaders occupy a vacant niche space in the recipient
      community, and the niche competition hypothesis states that invaders overlap with
      native species in niche space. Studies on trait similarity/dissimilarity between
      the invader and native species can provide information on their niche overlap.
      Here, we use the highly invasive and well-studied cane toad (Rhinella marina) to
      test these two hypotheses in Australia, and assess its degree of overlap with
      native species in several niche dimensions. We compare extensive morphological
      and environmental data of this successful invader to 235 species (97%) of native
      Australian frogs. Our study is the first to document the significant
      morphological differences between the invasive cane toad and a continent-wide
      frog radiation: despite significant environmental overlap, cane toads were
      distinct in body size and shape from most Australian frog species, suggesting
      that in addition to their previously documented phenotypic plasticity and wide
      environmental and trophic niche breadth, their unique shape also may have
      contributed to their success as an invasive species in Australia. Thus, the
      invasive success of cane toads in Australia may be explained through them
      successfully colonizing an empty niche among Australian anurans. Our results
      support that the cane toad's distinct morphology may have played a unique role in
      the invasiveness of this species in Australia, which coupled with a broad
      environmental niche breadth, would have boosted their ability to expand their
      distribution across Australia. We also propose RLLR (Relative limb length ratio)
      as a potentially useful measure of identifying morphological niche uniqueness and
      a potential measure of invasiveness potential in anuran amphibians.

PMID- 29043019
TI  - Effects of livestock grazing on rangeland biodiversity: A meta-analysis of grouse
      populations.
AB  - Livestock grazing affects over 60% of the world's agricultural lands and can
      influence rangeland ecosystem services and the quantity and quality of wildlife
      habitat, resulting in changes in biodiversity. Concomitantly, livestock grazing
      has the potential to be detrimental to some wildlife species while benefiting
      other rangeland organisms. Many imperiled grouse species require rangeland
      landscapes that exhibit diverse vegetation structure and composition to complete
      their life cycle. However, because of declining populations and reduced
      distributions, grouse are increasingly becoming a worldwide conservation concern.
      Grouse, as a suite of upland gamebirds, are often considered an umbrella species
      for other wildlife and thus used as indicators of rangeland health. With a
      projected increase in demand for livestock products, better information will be
      required to mitigate the anthropogenic effects of livestock grazing on rangeland
      biodiversity. To address this need, we completed a data-driven and systematic
      review of the peer-reviewed literature to determine the current knowledge of the
      effects of livestock grazing on grouse populations (i.e., chick production and
      population indices) worldwide. Our meta-analysis revealed an overall negative
      effect of livestock grazing on grouse populations. Perhaps more importantly, we
      identified an information void regarding the effects of livestock grazing on the
      majority of grouse species. Additionally, the reported indirect effects of
      livestock grazing on grouse species were inconclusive and more reflective of
      differences in the experimental design of the available studies. Future studies
      designed to evaluate the direct and indirect effects of livestock grazing on
      wildlife should document (i) livestock type, (ii) timing and frequency of
      grazing, (iii) duration, and (iv) stocking rate. Much of this information was
      lacking in the available published studies we reviewed, but is essential when
      making comparisons between different livestock grazing management practices and
      their potential impacts on rangeland biodiversity.

PMID- 29043020
TI  - Secondary invasion: When invasion success is contingent on other invaders
      altering the properties of recipient ecosystems.
AB  - Positive interactions between exotic species may increase ecosystem-level impacts
      and potentially facilitate the entry and spread of other exotic species. Invader
      facilitated invasion success-"secondary invasion"-is a key conceptual aspect of
      the well-known invasional meltdown hypothesis, but remains poorly defined and
      empirically underexplored. Drawing from heuristic models and published empirical
      studies, we explore this form of "secondary invasion" and discuss the phenomenon
      within the recognized conceptual framework of the determinants of invasion
      success. The term "secondary invasion" has been used haphazardly in the
      literature to refer to multiple invasion phenomena, most of which have other more
      accepted titles. Our usage of the term secondary invasion is akin to "invader
      facilitated invasion," which we define as the phenomenon in which the invasion
      success of one exotic species is contingent on the presence, influence, and
      impacts of one or more other exotic species. We present case studies of secondary
      invasion whereby primary invaders facilitate the entry or establishment of exotic
      species into communities where they were previously excluded from becoming
      invasive. Our synthesis, discussion, and conceptual framework of this type of
      secondary invasion provides a useful reference to better explain how invasive
      species can alter key properties of recipient ecosystems that can ultimately
      determine the invasion success of other species. This study increases our
      appreciation for complex interactions following invasion and highlights the
      impacts of invasive species themselves as possible determinants of invasion
      success. We anticipate that highlighting "secondary invasion" in this way will
      enable studies reporting similar phenomena to be identified and linked through
      consistent terminology.

PMID- 29043021
TI  - Genetic wealth, population health: Major histocompatibility complex variation in
      captive and wild ring-tailed lemurs (Lemur catta).
AB  - Across species, diversity at the major histocompatibility complex (MHC) is
      critical to individual disease resistance and, hence, to population health;
      however, MHC diversity can be reduced in small, fragmented, or isolated
      populations. Given the need for comparative studies of functional genetic
      diversity, we investigated whether MHC diversity differs between populations
      which are open, that is experiencing gene flow, versus populations which are
      closed, that is isolated from other populations. Using the endangered ring-tailed
      lemur (Lemur catta) as a model, we compared two populations under long-term
      study: a relatively "open," wild population (n = 180) derived from Beza Mahafaly
      Special Reserve, Madagascar (2003-2013) and a "closed," captive population (n =
      121) derived from the Duke Lemur Center (DLC, 1980-2013) and from the
      Indianapolis and Cincinnati Zoos (2012). For all animals, we assessed MHC-DRB
      diversity and, across populations, we compared the number of unique MHC-DRB
      alleles and their distributions. Wild individuals possessed more MHC-DRB alleles
      than did captive individuals, and overall, the wild population had more unique
      MHC-DRB alleles that were more evenly distributed than did the captive
      population. Despite management efforts to maintain or increase genetic diversity
      in the DLC population, MHC diversity remained static from 1980 to 2010. Since
      2010, however, captive-breeding efforts resulted in the MHC diversity of
      offspring increasing to a level commensurate with that found in wild individuals.
      Therefore, loss of genetic diversity in lemurs, owing to small founder
      populations or reduced gene flow, can be mitigated by managed breeding efforts.
      Quantifying MHC diversity within individuals and between populations is the
      necessary first step to identifying potential improvements to captive management
      and conservation plans.

PMID- 29043022
TI  - Using genetic tools to estimate the prevalence of non-native red deer (Cervus
      elaphus) in a Western European population.
AB  - Game species like the red deer have been subjected to anthropogenic impacts for
      centuries. Translocations are often carried out-sometimes illegally-not only for
      sporting purposes, but also to increase trophy quality, reduce inbreeding, or
      mitigate bottlenecks after excessive persecution. Apart from the blurring of
      large-scale genetic structure, translocations without adequate quarantine measure
      risk introducing pathogens into potentially immunologically naive populations. It
      is therefore important to understand the frequency of clandestine translocations.
      Identification of non-autochthonous animals and their potential origin is often
      difficult and, in red deer, has been hampered by the lack of large-scale
      genotypic datasets for comparison. In the present study, we make use of a
      recently published European-wide microsatellite dataset to detect and quantify
      the presence of non-autochthonous red deer in a large population sample (n =
      1,780) from Central Europe (Belgium). Using factorial correspondence analysis,
      assignment tests and Bayesian clustering algorithms we arrive at an estimate of
      3.7% non-autochthonous animals (or their descendants). Some of these animals were
      assigned to a nearby French population and may have immigrated into Belgium
      naturally, but the large majority must have been introduced by humans. Our
      analysis pointed to the British Isles and Germany/Poland as the potential origin
      of many introduced deer, regions known to have been source populations for
      translocations in Europe and beyond. We found evidence for recreational hunters
      using carcasses from farmed deer to fulfill mandatory hunting quotas. Our study
      is the first to quantify the extent of human-mediated introductions in a European
      game species at such a large scale with large and representative sample sizes.

PMID- 29043023
TI  - Sapling growth rates reveal conspecific negative density dependence in a
      temperate forest.
AB  - Local tree species diversity is maintained in part by conspecific negative
      density dependence (CNDD). This pervasive mechanism occurs in a variety of forms
      and ecosystems, but research to date has been heavily skewed toward tree seedling
      survival in tropical forests. To evaluate CNDD more broadly, we investigated how
      sapling growth rates were affected by conspecific adult neighbors in a fully
      mapped 25.6 ha temperate deciduous forest. We examined growth rates as a function
      of the local adult tree neighborhood (via spatial autoregressive modeling) and
      compared the spatial positioning of faster-growing and slower-growing saplings
      with respect to adult conspecific and heterospecific trees (via bivariate point
      pattern analysis). In addition, to determine whether CNDD-driven variation in
      growth rates leaves a corresponding spatial signal, we extended our point pattern
      analysis to a static, growth-independent comparison of saplings and the next
      larger size class. We found that negative conspecific effects on sapling growth
      were most prevalent. Five of the nine species that were sufficiently abundant for
      analysis exhibited CNDD, while only one species showed evidence of a positive
      conspecific effect, and one or two species, depending on the analysis, displayed
      heterospecific effects. There was general agreement between the autoregressive
      models and the point pattern analyses based on sapling growth rates, but point
      pattern analyses based on single-point-in-time size classes yielded results that
      differed markedly from the other two approaches. Our work adds to the growing
      body of evidence that CNDD is an important force in temperate forests, and
      demonstrates that this process extends to sapling growth rates. Further, our
      findings indicate that point pattern analyses based solely on size classes may
      fail to detect the process of interest (e.g., neighborhood-driven variation in
      growth rates), in part due to the confounding of tree size and age.

PMID- 29043024
TI  - Validating distribution models for twelve endemic bird species of tropical dry
      forest in western Mexico.
AB  - Considering the high biodiversity and conservation concerns of the tropical dry
      forest, this study aim is to predict and evaluate the potential and current
      distributions of twelve species of endemic birds which distribute along the
      western slope of Mexico. The main goal is to evaluate altogether different
      methods for predicting actual species distribution models (ADMs) of the twelve
      species including the identification of key environmental potential limiting
      factors. ADMs for twelve endemic Mexican birds were generated and validated by
      means of applying: (1) three widely used species niche modeling approaches (ENFA,
      Garp, and Maxent); (2) two thresholding methods, based on ROC curves and Kappa
      Index, for transforming continuous models to presence/absence (binary) models;
      (3) documented habitat-species associations for reducing species potential
      distribution models (PDMs); and (4) field occurrence data for validating final
      ADMs. Binary PDMs' predicted areas seemed overestimated, while ADMs looked
      drastically reduced and fragmented because of the approach taken for eliminating
      those predicted areas which were documented as unsuitable habitat types for
      individual species. Results indicated that both thresholding methods generated
      similar threshold values for species modeled by each of the three species
      distribution modeling algorithms (SDMAs). A Wilcoxon signed-rank test, however,
      showed that Kappa values were generally higher than ROC curve for species modeled
      by ENFA and Maxent, while for Garp models there were no significant differences.
      Prediction success (e.g., true presences percentage) obtained from field
      occurrence data revealed a range of 50%-82% among the 12 species. The three
      modeling approaches applied enabled to test the application of two thresholding
      methods for transforming continuous to binary (presence/absence) models. The use
      of documented habitat preferences resulted in drastic reductions and
      fragmentation of PDMs. However, ADMs predictive success rate, tested using field
      species occurrence data, varied between 50 and 82%.

PMID- 29043025
TI  - Diversity and distribution of genetic variation in gammarids: Comparing patterns
      between invasive and non-invasive species.
AB  - Biological invasions are worldwide phenomena that have reached alarming levels
      among aquatic species. There are key challenges to understand the factors behind
      invasion propensity of non-native populations in invasion biology. Interestingly,
      interpretations cannot be expanded to higher taxonomic levels due to the fact
      that in the same genus, there are species that are notorious invaders and those
      that never spread outside their native range. Such variation in invasion
      propensity offers the possibility to explore, at fine-scale taxonomic level, the
      existence of specific characteristics that might predict the variability in
      invasion success. In this work, we explored this possibility from a molecular
      perspective. The objective was to provide a better understanding of the genetic
      diversity distribution in the native range of species that exhibit contrasting
      invasive propensities. For this purpose, we used a total of 784 sequences of the
      cytochrome c oxidase subunit I of mitochondrial DNA (mtDNA-COI) collected from
      seven Gammaroidea, a superfamily of Amphipoda that includes species that are both
      successful invaders (Gammarus tigrinus, Pontogammarus maeoticus, and
      Obesogammarus crassus) and strictly restricted to their native regions (Gammarus
      locusta, Gammarus salinus, Gammarus zaddachi, and Gammarus oceanicus). Despite
      that genetic diversity did not differ between invasive and non-invasive species,
      we observed that populations of non-invasive species showed a higher degree of
      genetic differentiation. Furthermore, we found that both geographic and
      evolutionary distances might explain genetic differentiation in both non-native
      and native ranges. This suggests that the lack of population genetic structure
      may facilitate the distribution of mutations that despite arising in the native
      range may be beneficial in invasive ranges. The fact that evolutionary distances
      explained genetic differentiation more often than geographic distances points
      toward that deep lineage divergence holds an important role in the distribution
      of neutral genetic diversity.

PMID- 29043026
TI  - Predators do not spill over from forest fragments to maize fields in a landscape
      mosaic in central Argentina.
AB  - South America is undergoing a rapid and large-scale conversion of natural
      habitats to cultivated land. Ecosystem services still remain important but their
      level and sustainability are not known. We quantified predation intensity in an
      Argentinian agricultural landscape containing remnants of the original chaco
      serrano forest using artificial sentinel prey. We sought to identify the main
      predators and the effect of landscape configuration and maize phenology on
      predation pressure by invertebrate and vertebrate predators in this landscape.
      The most common predators were chewing insects (50.4% predation events), birds
      (22.7%), and ants (17.5%). Overall predation rates in forest fragments (41.6% per
      day) were significantly higher than in the surrounding maize fields (21.5% per
      day). Invertebrate predation was higher inside and at the edge of forest
      fragments than within fields, and did not change with increasing distance from a
      fragment edge, indicating a lack of spillover from the native habitat remnants to
      the cultivated matrix at the local scale. Distance from a continuous forest had a
      positive impact on predation by invertebrates and a negative impact on vertebrate
      predation.

PMID- 29043027
TI  - Genetic diversity and sex-bias dispersal of plateau pika in Tibetan plateau.
AB  - Dispersal is an important aspect in organism's life history which could influence
      the rate and outcome of evolution of organism. Plateau pika is the keystone
      species in community of grasslands in Tibetan Plateau. In this study, we combine
      genetic and field data to character the population genetic pattern and dispersal
      dynamics in plateau pika (Ochotona curzoniae). Totally, 1,352 individual samples
      were collected, and 10 microsatellite loci were analyzed. Results revealed that
      plateau pika possessed high genetic diversity and inbreeding coefficient in a
      fine-scale population. Dispersal distance is short and restricted in about 20 m.
      An effective sex-biased dispersal strategy is employed by plateau pika: males
      disperse in breeding period for mating while females do it after reproduction for
      offspring and resource. Inbreeding avoiding was shown as the common driving force
      of dispersal, together with the other two factors, environment and resource. In
      addition, natal dispersal is female biased. More detailed genetic analyzes are
      needed to confirm the role of inbreeding avoidance and resource competition as
      ultimate cause of dispersal patterns in plateau pika.

PMID- 29043028
TI  - Enhanced effects of biotic interactions on predicting multispecies spatial
      distribution of submerged macrophytes after eutrophication.
AB  - Water eutrophication creates unfavorable environmental conditions for submerged
      macrophytes. In these situations, biotic interactions may be particularly
      important for explaining and predicting the submerged macrophytes occurrence.
      Here, we evaluate the roles of biotic interactions in predicting spatial
      occurrence of submerged macrophytes in 1959 and 2009 for Dianshan Lake in eastern
      China, which became eutrophic since the 1980s. For the four common species
      occurred in 1959 and 2009, null species distribution models based on abiotic
      variables and full models based on both abiotic and biotic variables were
      developed using generalized linear model (GLM) and boosted regression trees (BRT)
      to determine whether the biotic variables improved the model performance.
      Hierarchical Bayesian-based joint species distribution models capable of
      detecting paired biotic interactions were established for each species in both
      periods to evaluate the changes in the biotic interactions. In most of the GLM
      and BRT models, the full models showed better performance than the null models in
      predicting the species presence/absence, and the relative importance of the
      biotic variables in the full models increased from less than 50% in 1959 to more
      than 50% in 2009 for each species. Moreover, co-occurrence correlation of each
      paired species interaction was higher in 2009 than that in 1959. The findings
      suggest biotic interactions that tend to be positive play more important roles in
      the spatial distribution of multispecies assemblages of macrophytes and should be
      included in prediction models to improve prediction accuracy when forecasting
      macrophytes' distribution under eutrophication stress.

PMID- 29043029
TI  - Prevalence and genetic diversity of Batrachochytrium dendrobatidis in Central
      African island and continental amphibian communities.
AB  - The fungal pathogen Batrachochytrium dendrobatidis (Bd) infects hundreds of
      amphibian species and is implicated in global amphibian declines. Bd is comprised
      of several lineages that differ in pathogenicity, thus, identifying which Bd
      strains are present in a given amphibian community is essential for understanding
      host-pathogen dynamics. The presence of Bd has been confirmed in Central Africa,
      yet vast expanses of this region have not yet been surveyed for Bd prevalence,
      and the genetic diversity of Bd is largely unknown in this part of the world.
      Using retrospective surveys of museum specimens and contemporary field surveys,
      we estimated the prevalence of Bd in Central African island and continental
      amphibian assemblages, and genotyped strains of Bd present in each community. Our
      sampling of museum specimens included just a few individuals collected in the
      Gulf of Guinea archipelago prior to 1998, yet one of these individuals was Bd
      positive indicating that the pathogen has been on Bioko Island since 1966. We
      detected Bd across all subsequent sample years in our study and found modest
      support for a relationship between host life history and Bd prevalence, a
      positive relationship between prevalence and host community species richness, and
      no significant relationship between elevation and prevalence. The Global
      Panzootic Lineage (Bd GPL) was present in all the island and continental
      amphibian communities we surveyed. Our results are consistent with a long-term
      and widespread distribution of Bd in amphibian communities of Gabon and the Gulf
      of Guinea archipelago.

PMID- 29043030
TI  - The effect of nitrogen availability and water conditions on competition between a
      facultative CAM plant and an invasive grass.
AB  - Plants with crassulacean acid metabolism (CAM) are increasing their abundance in
      drylands worldwide. The drivers and mechanisms underlying the increased dominance
      of CAM plants and CAM expression (i.e., nocturnal carboxylation) in facultative
      CAM plants, however, remain poorly understood. We investigated how nutrient and
      water availability affected competition between Mesembryanthemum crystallinum (a
      model facultative CAM species) and the invasive C3 grass Bromus mollis that co
      occur in California's coastal grasslands. Specifically we investigated the extent
      to which water stress, nutrients, and competition affect nocturnal carboxylation
      in M. crystallinum. High nutrient and low water conditions favored M.
      crystallinum over B. mollis, in contrast to high water conditions. While low
      water conditions induced nocturnal carboxylation in 9-week-old individuals of M.
      crystallinum, in these low water treatments, a 66% reduction in nutrient applied
      over the entire experiment did not further enhance nocturnal carboxylation. In
      high water conditions M. crystallinum both alone and in association with B.
      mollis did not perform nocturnal carboxylation, regardless of the nutrient
      levels. Thus, nocturnal carboxylation in M. crystallinum was restricted by strong
      competition with B. mollis in high water conditions. This study provides
      empirical evidence of the competitive advantage of facultative CAM plants over
      grasses in drought conditions and of the restricted ability of M. crystallinum to
      use their photosynthetic plasticity (i.e., ability to switch to CAM behavior) to
      compete with grasses in well-watered conditions. We suggest that a high drought
      tolerance could explain the increased dominance of facultative CAM plants in a
      future environment with increased drought and nitrogen deposition, while the
      potential of facultative CAM plants such as M. crystallinum to expand to wet
      environments is expected to be limited.

PMID- 29043031
TI  - Postbreeding elevational movements of western songbirds in Northern California
      and Southern Oregon.
AB  - Migratory species employ a variety of strategies to meet energetic demands of
      postbreeding molt. As such, at least a few species of western Neotropical
      migrants are known to undergo short-distance upslope movements to locations where
      adults molt body and flight feathers (altitudinal molt migration). Given inherent
      difficulties in measuring subtle movements of birds occurring in western
      mountains, we believe that altitudinal molt migration may be a common yet poorly
      documented phenomenon. To examine prevalence of altitudinal molt migration, we
      used 29 years of bird capture data in a series of linear mixed-effect models for
      nine commonly captured species that breed in northern California and southern
      Oregon. Candidate models were formulated a priori to examine whether elevation
      and distance from the coast can be used to predict abundance of breeding and
      molting birds. Our results suggest that long-distance migrants such as Orange
      crowned Warbler (Oreothlypis celata) moved higher in elevation and Audubon's
      Warbler (Setophaga coronata) moved farther inland to molt after breeding.
      Conversely, for resident and short-distance migrants, we found evidence that
      birds either remained on the breeding grounds until they finished molting, such
      as Song Sparrow (Melospiza melodia) or made small downslope movements, such as
      American Robin (Turdus migratorius). We conclude that altitudinal molt migration
      may be a common, variable, and complex behavior among western songbird
      communities and is related to other aspects of a species' natural history, such
      as migratory strategy.

PMID- 29043032
TI  - Tracing coco de mer's reproductive history: Pollen and nutrient limitations
      reduce fecundity.
AB  - Habitat degradation can reduce or even prevent the reproduction of previously
      abundant plant species. To develop appropriate management strategies, we need to
      understand the reasons for reduced recruitment in degraded ecosystems. The
      dioecious coco de mer palm (Lodoicea maldivica) produces by far the largest seeds
      of any plant. It is a keystone species in an ancient palm forest that occurs only
      on two small islands in the Seychelles, yet contemporary rates of seed production
      are low, especially in fragmented populations. We developed a method to infer the
      recent reproductive history of female trees from morphological evidence present
      on their inflorescences. We then applied this method to investigate the effects
      of habitat disturbance and soil nutrient conditions on flower and fruit
      production. The 57 female trees in our sample showed a 19.5-fold variation in
      flower production among individuals over a seven-year period. Only 77.2% of trees
      bore developing fruits (or had recently shed fruits), with the number per tree
      ranging from zero to 43. Flower production was positively correlated with
      concentrations of available soil nitrogen and potassium and did not differ
      significantly between closed and degraded habitat. Fruiting success was
      positively correlated with pollen availability, as measured by numbers and
      distance of neighboring male trees. Fruit set was lower in degraded habitat than
      in closed forest, while the proportion of abnormal fruits that failed to develop
      was higher in degraded habitat. Seed size recorded for a large sample of seeds
      collected by forest wardens varied widely, with fresh weights ranging from 1 to
      18 kg. Synthesis: Shortages of both nutrients and pollen appear to limit seed
      production of Lodoicea in its natural habitat, with these factors affecting
      different stages of the reproductive process. Flower production varies widely
      amongst trees, while seed production is especially low in degraded habitat. The
      size of seeds is also very variable. We discuss the implications of these
      findings for managing this ecologically and economically important species.

PMID- 29043033
TI  - Behavior and season affect crayfish detection and density inference using
      environmental DNA.
AB  - Although the presence/absence of aquatic invertebrates using environmental DNA
      (eDNA) has been established for several species, inferring population densities
      has remained problematic. The invasive American signal crayfish, Pacifastacus
      leniusculus (Dana), is the leading cause of decline in the UK's only native
      crayfish species, Austropotamobius pallipes (Lereboullet). Methods to detect
      species at low abundances offer the opportunity for the early detection, and
      potential eradication, of P. leniusculus before population densities reach
      threatening levels in areas occupied by A. pallipes. Using a factorial
      experimental design with aquaria, we investigated the impacts of biomass, sex
      ratio, and fighting behavior on the amount of eDNA released by P. leniusculus,
      with the aim to infer density per aquarium depending on treatments. The amount of
      target eDNA in water samples from each aquarium was measured using the
      quantitative Polymerase Chain Reaction. We show that the presence of eggs
      significantly increases the concentration of crayfish eDNA per unit of mass, and
      that there is a significant relationship between eDNA concentration and biomass
      when females are egg-bearing. However, the relationship between crayfish biomass
      and eDNA concentration is lost in aquaria without ovigerous females. Female
      specific tanks had significantly higher eDNA concentrations than male-specific
      tanks, and the prevention of fighting did not impact the amount of eDNA in the
      water. These results indicate that detection and estimate of crayfish abundance
      using eDNA may be more effective while females are ovigerous. This information
      should guide further research for an accurate estimation of crayfish biomass in
      the field depending on the season. Our results indicate that detection and
      quantification of egg-laying aquatic invertebrate species using eDNA could be
      most successful during periods when eggs are developing in the water. We
      recommend that practitioners consider the reproductive cycle of target species
      when attempting to study or detect aquatic species using eDNA in the field.

PMID- 29043034
TI  - Sea level rise may increase extinction risk of a saltmarsh ontogenetic habitat
      specialist.
AB  - Specialist species are more vulnerable to environmental change than generalist
      species. For species with ontogenetic niche shifts, specialization may occur at a
      particular life stage making those stages more susceptible to environmental
      change. In the salt marshes in the northeast U.S., accelerated sea level rise is
      shifting vegetation patterns from flood-intolerant species such as Spartina
      patens to the flood-tolerant Spartina alterniflora. We tested the potential
      impact of this change on the coffee bean snail, Melampus bidentatus, a
      numerically dominant benthic invertebrate with an ontogenetic niche shift. From a
      survey of eight marshes throughout the northeast U.S., small snails were found
      primarily in S. patens habitats, and large snails were found primarily in stunted
      S. alterniflora habitats. When transplanted into stunted S. alterniflora, small
      snails suffered significantly higher mortality relative to those in S. patens
      habitats; adult snail survivorship was similar between habitats. Because other
      habitats were not interchangeable with S. patens for young snails, these results
      suggest that Melampus is an ontogenetic specialist where young snails are habitat
      specialists and adult snails are habitat generalists. Temperature was
      significantly higher and relative humidity significantly lower in stunted S.
      alterniflora than in S. patens. These data suggest that thermal and desiccation
      stress restricted young snails to S. patens habitat, which has high stem density
      and a layer of thatch that protects snails from environmental stress. Other
      authors predict that if salt marshes in the northeast U.S. are unable to migrate
      landward, sea level rise will eliminate S. patens habitats. We suggest that if a
      salt marsh loses its S. patens habitats, it will also lose its coffee bean
      snails. Our results demonstrate the need to consider individual life stages when
      determining a species' vulnerability to global change.

PMID- 29043035
TI  - Insights into the Vitis complex in the Danube floodplain (Austria).
AB  - European grapevine populations quickly disappeared from most of their range,
      massively killed by the spread of North American grapevine pests and diseases.
      Nowadays taxonomic pollution represents a new threat. A large Vitis complex
      involves escaped cultivars, rootstocks, and wild grapevines. The study aimed to
      provide insight into the Vitis complex in the Danube region through field and
      genetic analyses. Among the five other major rivers in Europe which still host
      wild grapevine populations, the Danube floodplain is the only one benefiting from
      an extensive protected forest area (93 km2) and an relatively active dynamic
      flood pulse. The Donau-Auen National Park also regroups the largest wild
      grapevine population in Europe. Ninety-two percent of the individuals collected
      in the park were true wild grapevines, and 8% were hybrids and introgressed
      individuals of rootstocks, wild grapevines, and cultivars. These three groups are
      interfertile acting either as pollen donor or receiver. Hybrids were established
      within and outside the dykes, mostly in anthropized forest edges. The best
      developed individuals imply rootstock genes. They establish in the most erosive
      parts of the floodplain. 42% of the true wild grapevines lived at the edges of
      forest/meadow, 33.3% at the edges forest/channels, and 23.9% in forest gaps. DBH
      (Diameter Breast Height) varied significantly with the occurrence of flooding.
      Clones were found in both true wild and hybrids/introgressed grapevines. The
      process of cloning seemed to be prevented in places where flooding dynamics is
      reduced. The current global distribution of true wild grapevines shows a strong
      tendency toward clustering, in sites where forestry practices were the most
      extensive. However, the reduced flooding activity is a danger for long-term
      sustainability of the natural wild grapevine population.

PMID- 29043036
TI  - Quantifying ecosystem service trade-offs for plantation forest management to
      benefit provisioning and regulating services.
AB  - There is increasing interest worldwide regarding managing plantation forests in a
      manner that maintains or improves timber production, enhances ecosystem services,
      and promotes long-term sustainability of forest resources. We selected the Gan
      River Basin, the largest catchment of Poyang Lake and a region with a typical
      plantation distribution in South China, as the study region. We evaluated and
      mapped four important forest ecosystem services, including wood volume, carbon
      storage, water yield, and soil retention at a 30 * 30 m resolution, then
      quantified their trade-offs and synergies at the county and subwatershed scales.
      We found that the wood volume and carbon storage services, as well as the soil
      retention and water yield, exhibited synergistic relationships. However, the
      carbon storage displayed a trade-off relationship with the water yield.
      Additionally, we compared the beneficial spatial characteristics among dominant
      species in the study region. The results showed that the Chinese fir forest and
      the pine forest exhibited lower overall benefits than natural forests including
      the broad-leaved forest and the bamboo forest. To propose a suitable management
      strategy for the study region, method of spatial cluster analysis was used based
      on the four eco-services at the subwatershed scale. The basin was divided into
      four management groups instead of treating the region as a homogenous management
      region. Finally, we proposed more specific and diverse management strategies to
      optimize forest benefits throughout the entire region.

PMID- 29043037
TI  - Sperm whale dive behavior characteristics derived from intermediate-duration
      archival tag data.
AB  - Here, we describe the diving behavior of sperm whales (Physeter macrocephalus)
      using the Advanced Dive Behavior (ADB) tag, which records depth data at 1-Hz
      resolution and GPS-quality locations for over 1 month, before releasing from the
      whale for recovery. A total of 27 ADB tags were deployed on sperm whales in the
      central Gulf of California, Mexico, during spring 2007 and 2008, of which 10 were
      recovered for data download. Tracking durations of all tags ranged from 0 to 34.5
      days (median = 2.3 days), and 0.6 to 26.6 days (median = 5.0 days) for recovered
      tags. Recovered tags recorded a median of 50.8 GPS-quality locations and 42.6
      dives per day. Dive summary metrics were generated for archived dives and were
      subsequently classified into six categories using hierarchical cluster analysis.
      A mean of 77% of archived dives per individual were one of four dive categories
      with median Maximum Dive Depth >290 m (V-shaped, Mid-water, Benthic, or
      Variable), likely associated with foraging. Median Maximum Dive Depth was <30 m
      for the other two categories (Short- and Long-duration shallow dives), likely
      representing socializing or resting behavior. Most tagged whales remained near
      the tagging area during the tracking period, but one moved north of Isla Tiburon,
      where it appeared to regularly dive to, and travel along the seafloor. Three
      whales were tagged on the same day in 2007 and subsequently traveled in close
      proximity (<1 km) for 2 days. During this period, the depth and timing of their
      dives were not coordinated, suggesting they were foraging on a vertically
      heterogeneous prey field. The multiweek dive records produced by ADB tags enabled
      us to generate a robust characterization of the diving behavior, activity budget,
      and individual variation for an important predator of the mesopelagos over
      temporal and spatial scales not previously possible.

PMID- 29043038
TI  - Habitat niche breadth predicts invasiveness in solitary ascidians.
AB  - A major focus of invasion biology is understanding the traits associated with
      introduction success. Most studies assess these traits in the invaded region,
      while only few compare nonindigenous species to the pool of potential invaders in
      their native region. We focused on the niche breadth hypothesis, commonly evoked
      but seldom tested, which states that generalist species are more likely to become
      introduced as they are capable of thriving under a wide set of conditions. Based
      on the massive introduction of tropical species into the Mediterranean via the
      Suez Canal (Lessepsian migration), we defined ascidians in the Red Sea as the
      pool of potential invaders. We constructed unique settlement plates, each
      representing six different niches, to assess ascidian niche breadth, and deployed
      them in similar habitats in the native and invaded regions. For each species
      found on plates, we evaluated its abundance, relative abundance across
      successional stages, and niche breadth, and then compared (1) species in the Red
      Sea known to have been introduced into the Mediterranean (Lessepsian species) and
      those not known from the Mediterranean (non-Lessepsian); and (2) nonindigenous
      and indigenous species in the Mediterranean. Lessepsian species identified on
      plates in the Red Sea demonstrated wider niche breadth than non-Lessepsian
      species, supporting the niche breadth hypothesis within the native region. No
      differences were found between Lessepsian and non-Lessepsian species in species
      abundance and successional stages. In the Mediterranean, nonindigenous species
      numerically dominated the settlement plates. This precluded robust comparisons of
      niche breadth between nonindigenous and indigenous species in the invaded region.
      In conclusion, using Red Sea ascidians as the pool of potential invaders, we
      found clear evidence supporting the niche breadth hypothesis in the native
      region. We suggest that such patterns may often be obscured when conducting trait
      based studies in the invaded regions alone. Our findings indicate that
      quantifying the niche breadth of species in their native regions will improve
      estimates of invasiveness potential.

PMID- 29043039
TI  - Recovery of plant communities after ecological restoration of forestry-drained
      peatlands.
AB  - Ecological restoration is expected to reverse the loss of biodiversity and
      ecosystem services. Due to the low number of well-replicated field studies, the
      extent to which restoration recovers plant communities, and the factors
      underlying possible shortcomings, are not well understood even in medium term. We
      compared the plant community composition of 38 sites comprising pristine,
      forestry-drained, and 5 or 10 years ago restored peatlands in southern Finland,
      with special interest in understanding spatial variation within studied sites, as
      well as the development of the numbers and the abundances of target species. Our
      results indicated a recovery of community composition 5-10 years after
      restoration, but there was significant heterogeneity in recovery. Plant
      communities farthest away from ditches were very similar to their pristine
      reference already 10 years after restoration. In contrast, communities in the
      ditches were as far from the target as the drained communities. The recovery
      appears to be characterized by a decline in the number and abundance of species
      typical to degraded conditions, and increase in the abundance of characteristic
      peatland species. However, we found no increase above the drained state in the
      number of characteristic peatland species. Our results suggest that there is a
      risk of drawing premature conclusions on the efficiency of ecological restoration
      with the current practice of short-term monitoring. Our results also illustrate
      fine-scale within-site spatial variability in the degradation and recovery of the
      plant communities that should be considered when evaluating the success of
      restoration. Overall, we find the heterogeneous outcome of restoration observed
      here promising. However, low recovery in the number of characteristic species
      demonstrates the importance of prioritizing restoration sites, and addressing the
      uncertainty of recovery when setting restoration targets. It appears that it is
      easier to eradicate unwanted species than regain characteristic species by
      restoration.

PMID- 29043040
TI  - Marine protected area restricts demographic connectivity: Dissimilarity in a
      marine environment can function as a biological barrier.
AB  - The establishment of marine protected areas (MPAs) can often lead to
      environmental differences between MPAs and fishing zones. To determine the
      effects on marine dispersal of environmental dissimilarity between an MPA and
      fishing zone, we examined the abundance and recruitment patterns of two
      anemonefishes (Amphiprion frenatus and A. perideraion) that inhabit sea anemones
      in different management zones (i.e., an MPA and two fishing zones) by performing
      a field survey and a genetic parentage analysis. We found lower levels of
      abundance per anemone in the MPA compared to the fishing zones for both species
      (n = 1,525 anemones, p = .032). The parentage analysis also showed that lower
      numbers of fishes were recruited from the fishing zones and outside of the study
      area into each anemone in the MPA than into each anemone in the fishing zones (n
      = 1,525 anemones, p < .017). However, the number of self-recruit production per
      female did not differ between the MPA and fishing zones (n = 384 females, p =
      .516). Because the ocean currents around the study site were unlikely to cause a
      lower settlement intensity of larvae in the MPA, the ocean circulation was not
      considered crucial to the observed abundance and recruitment patterns. Instead,
      stronger top-down control and/or a lower density of host anemones in the MPA were
      potential factors for such patterns. Our results highlight the importance of
      dissimilarity in a marine environment as a factor that affects connectivity.

PMID- 29043041
TI  - Riverine fish diversity varies according to geographical isolation and land use
      modification.
AB  - Understanding the environmental factors driving species-genetic diversity
      correlations (SGDCs) is critical for designing appropriate conservation and
      management strategies to protect biodiversity. Yet, few studies have explored the
      impact of changing land use patterns on SGDCs specifically in aquatic
      communities. This study examined patterns of genetic diversity in roach (Rutilus
      rutilus L.) together with fish species composition across 19 locations in a large
      river catchment, spanning a gradient in land use. Our findings show significant
      correlations between some, but not all, species and genetic diversity end points.
      For example, genetic and species differentiation showed a weak but significant
      linear relationship across the Thames catchment, but additional diversity
      measures such as allelic richness and fish population abundance did not. Further
      examination of patterns in species and genetic diversity indicated that land use
      intensification has a modest effect on fish diversity compared to the combined
      influence of geographical isolation and land use intensification. These results
      indicate that environmental changes in riparian habitats have the potential to
      amplify shifts in the composition of stream fish communities in poorly connected
      river stretches. Conservation and management strategies for fish populations
      should, therefore, focus on enhancing connectivity between river stretches and
      limit conversion of nearby land to arable or urban use to maintain current levels
      of biodiversity.

PMID- 29043042
TI  - feedr and animalnexus.ca: A paired R package and user-friendly Web application
      for transforming and visualizing animal movement data from static stations.
AB  - Radio frequency identification (RFID) provides a simple and inexpensive approach
      for examining the movements of tagged animals, which can provide information on
      species behavior and ecology, such as habitat/resource use and social
      interactions. In addition, tracking animal movements is appealing to naturalists,
      citizen scientists, and the general public and thus represents a tool for public
      engagement in science and science education. Although a useful tool, the large
      amount of data collected using RFID may quickly become overwhelming. Here, we
      present an R package (feedr) we have developed for loading, transforming, and
      visualizing time-stamped, georeferenced data, such as RFID data collected from
      static logger stations. Using our package, data can be transformed from raw RFID
      data to visits, presence (regular detections by a logger over time), movements
      between loggers, displacements, and activity patterns. In addition, we provide
      several conversion functions to allow users to format data for use in functions
      from other complementary R packages. Data can also be visualized through static
      or interactive maps or as animations over time. To increase accessibility, data
      can be transformed and visualized either through R directly, or through the
      companion site: http://animalnexus.ca, an online, user-friendly, R-based Shiny
      Web application. This system can be used by professional and citizen scientists
      alike to view and study animal movements. We have designed this package to be
      flexible and to be able to handle data collected from other stationary sources
      (e.g., hair traps, static very high frequency (VHF) telemetry loggers,
      observations of marked individuals in colonies or staging sites), and we hope
      this framework will become a meeting point for science, education, and community
      awareness of the movements of animals. We aim to inspire citizen engagement while
      simultaneously enabling robust scientific analysis.

PMID- 29043043
TI  - A pantropical analysis of the impacts of forest degradation and conversion on
      local temperature.
AB  - Temperature is a core component of a species' fundamental niche. At the fine
      scale over which most organisms experience climate (mm to ha), temperature
      depends upon the amount of radiation reaching the Earth's surface, which is
      principally governed by vegetation. Tropical regions have undergone widespread
      and extreme changes to vegetation, particularly through the degradation and
      conversion of rainforests. As most terrestrial biodiversity is in the tropics,
      and many of these species possess narrow thermal limits, it is important to
      identify local thermal impacts of rainforest degradation and conversion. We
      collected pantropical, site-level (<1 ha) temperature data from the literature to
      quantify impacts of land-use change on local temperatures, and to examine whether
      this relationship differed aboveground relative to belowground and between wet
      and dry seasons. We found that local temperature in our sample sites was higher
      than primary forest in all human-impacted land-use types (N = 113,894 daytime
      temperature measurements from 25 studies). Warming was pronounced following
      conversion of forest to agricultural land (minimum +1.6 degrees C, maximum +13.6
      degrees C), but minimal and nonsignificant when compared to forest degradation
      (e.g., by selective logging; minimum +1 degrees C, maximum +1.1 degrees C). The
      effect was buffered belowground (minimum buffering 0 degrees C, maximum buffering
      11.4 degrees C), whereas seasonality had minimal impact (maximum buffering 1.9
      degrees C). We conclude that forest-dependent species that persist following
      conversion of rainforest have experienced substantial local warming.
      Deforestation pushes these species closer to their thermal limits, making it more
      likely that compounding effects of future perturbations, such as severe droughts
      and global warming, will exceed species' tolerances. By contrast, degraded
      forests and belowground habitats may provide important refugia for thermally
      restricted species in landscapes dominated by agricultural land.

PMID- 29043044
TI  - Natives and non-natives plants show different responses to elevation and
      disturbance on the tropical high Andes of Ecuador.
AB  - The aim was to assess patterns of plant diversity in response to elevation and
      disturbance in a tropical mountain. The study area was located in north-central
      portion of the Eastern Cordillera of the Ecuadorian Andes, on a road from 1,150 m
      a.s.l. (Osayacu) to 4,000 (Papallacta). Along a mountain road spanning a wide
      altitudinal gradient, at 20 elevations we sampled three plots: one at the
      roadside and two perpendicular to the roadside. The relationship between
      elevation and species richness was assessed using linear and quadratic
      regressions, the effect of disturbance on species richness was determined by
      ANCOVA and a t test with parameters obtained from quadratic equations. Similarity
      of species composition among the roadside and sites distant was evaluated with
      the Chao-Jaccard and classic Jaccard similarity indices, the distribution of non
      native species according to their origin were analyzed with linear and quadratic
      regression. The native species showed a linearly monotonic decrease with
      elevation, whereas non-natives showed a quadratic distribution. Disturbed areas
      had the greatest number of non-native species and lower native species richness,
      showing also a high floristic similarity; less disturbed areas showed the
      opposite. The non-native species of temperate origin were more numerous and
      showed unimodal elevational distribution, while species of tropical origin were
      few and decreased linearly with elevation. We conclude that in a tropical
      highland mountain range, native and non-native plant species respond differently
      to elevation: native species exhibit a monotonically linear decrease, and non
      native species show a unimodal trend. Disturbance positively affects non-native
      species showing higher richness and fewer species turnover. In addition, the non
      native species are located along of the elevational gradient in relation to their
      biogeographic origin.

PMID- 29043045
TI  - RADseq dataset with 90% missing data fully resolves recent radiation of
      Petalidium (Acanthaceae) in the ultra-arid deserts of Namibia.
AB  - Deserts, even those at tropical latitudes, often have strikingly low levels of
      plant diversity, particularly within genera. One remarkable exception to this
      pattern is the genus Petalidium (Acanthaceae), in which 37 of 40 named species
      occupy one of the driest environments on Earth, the Namib Desert of Namibia and
      neighboring Angola. To contribute to understanding this enigmatic diversity, we
      generated RADseq data for 47 accessions of Petalidium representing 22 species. We
      explored the impacts of 18 different combinations of assembly parameters in de
      novo assembly of the data across nine levels of missing data plus a best practice
      assembly using a reference Acanthaceae genome for a total of 171 sequence
      datasets assembled. RADseq data assembled at several thresholds of missing data,
      including 90% missing data, yielded phylogenetic hypotheses of Petalidium that
      were confidently and nearly fully resolved, which is notable given that
      divergence time analyses suggest a crown age for African species of 3.6-1.4 Ma.
      De novo assembly of our data yielded the most strongly supported and well
      resolved topologies; in contrast, reference-based assembly performed poorly,
      perhaps due in part to moderate phylogenetic divergence between the reference
      genome, Ruellia speciosa, and the ingroup. Overall, we found that Petalidium,
      despite the harshness of the environment in which species occur, shows a net
      diversification rate (0.8-2.1 species per my) on par with those of diverse genera
      in tropical, Mediterranean, and alpine environments.

PMID- 29043046
TI  - Among-tree variability and feedback effects result in different growth responses
      to climate change at the upper treeline in the Swiss Alps.
AB  - Upper treeline ecotones are important life form boundaries and particularly
      sensitive to a warming climate. Changes in growth conditions at these ecotones
      have wide-ranging implications for the provision of ecosystem services in densely
      populated mountain regions like the European Alps. We quantify climate effects on
      short- and long-term tree growth responses, focusing on among-tree variability
      and potential feedback effects. Although among-tree variability is thought to be
      substantial, it has not been considered systematically yet in studies on growth
      climate relationships. We compiled tree-ring data including almost 600 trees of
      major treeline species (Larix decidua, Picea abies, Pinus cembra, and Pinus mugo)
      from three climate regions of the Swiss Alps. We further acquired tree size
      distribution data using unmanned aerial vehicles. To account for among-tree
      variability, we employed information-theoretic model selections based on linear
      mixed-effects models (LMMs) with flexible choice of monthly temperature effects
      on growth. We isolated long-term trends in ring-width indices (RWI) in
      interaction with elevation. The LMMs revealed substantial amounts of previously
      unquantified among-tree variability, indicating different strategies of single
      trees regarding when and to what extent to invest assimilates into growth.
      Furthermore, the LMMs indicated strongly positive temperature effects on growth
      during short summer periods across all species, and significant contributions of
      fall (L. decidua) and current year's spring (L. decidua, P. abies). In the longer
      term, all species showed consistently positive RWI trends at highest elevations,
      but different patterns with decreasing elevation. L. decidua exhibited even
      negative RWI trends compared to the highest treeline sites, whereas P. abies, P.
      cembra, and P. mugo showed steeper or flatter trends with decreasing elevation.
      This does not only reflect effects of ameliorated climate conditions on tree
      growth over time, but also reveals first signs of long-suspected negative and
      positive feedback of climate change on stand dynamics at treeline.

PMID- 29043047
TI  - Relationships between aboveground biomass and plant cover at two spatial scales
      and their determinants in northern Tibetan grasslands.
AB  - The relationships between cover and AGB for the dominant and widely distributed
      alpine grasslands on the northern Tibetan Plateau is still not fully examined.
      The objectives of this study are to answer the following question: (1) How does
      aboveground biomass (AGB) of alpine grassland relate to plant cover at different
      spatial scales? (2) What are the major biotic and abiotic factors influencing on
      AGB-cover relationship? A community survey (species, cover, height, and
      abundance) was conducted within 1 m * 1 m plots in 70 sites along a precipitation
      gradient of 50-600 m. Ordinary linear regression was employed to examine AGB
      cover relationships of both community and species levels at regional scale of
      entire grassland and landscape scale of alpine meadow, alpine steppe, and desert
      steppe. Hierarchical partitioning was employed to estimate independent
      contributions of biotic and abiotic factors to AGB and cover at both scales.
      Partial correlation analyses were used to discriminate the effects of biotic and
      abiotic factors on AGB-cover relationships at two spatial scales. AGB and
      community cover both exponentially increased along the precipitation gradient. At
      community level, AGB was positively and linearly correlated with cover for all
      grasslands except for alpine meadow. AGB was also linearly correlated with cover
      of species level at both regional and landscape scales. Contributions of biotic
      and abiotic factors to the relationship between AGB and cover significantly
      depended on spatial scales. Cover of cushions, forbs, legumes and sedges, species
      richness, MAP, and soil bulk density were important factors that influenced the
      AGB-cover relationship at either regional or landscape scale. This study
      indicated generally positive and linear relationships between AGB and cover are
      at both regional and landscape scales. Spatial scale may affect ranges of cover
      and modify the contribution of cover to AGB. AGB-cover relationships were
      influenced mainly by species composition of different functional groups.
      Therefore, in deriving AGB patterns at different spatial scales, community
      composition should be considered to obtain acceptable accuracy.

PMID- 29043048
TI  - Do temperate tree species diversity and identity influence soil microbial
      community function and composition?
AB  - Studies of biodiversity-ecosystem function in treed ecosystems have generally
      focused on aboveground functions. This study investigates intertrophic links
      between tree diversity and soil microbial community function and composition. We
      examined how microbial communities in surface mineral soil responded to
      experimental gradients of tree species richness (SR), functional diversity (FD),
      community-weighted mean trait value (CWM), and tree identity. The site was a 4
      year-old common garden experiment near Montreal, Canada, consisting of deciduous
      and evergreen tree species mixtures. Microbial community composition, community
      level physiological profiles, and respiration were evaluated using phospholipid
      fatty acid (PLFA) analysis and the MicroRespTM system, respectively. The
      relationship between tree species richness and glucose-induced respiration (GIR),
      basal respiration (BR), metabolic quotient (qCO 2) followed a positive but
      saturating shape. Microbial communities associated with species mixtures were
      more active (basal respiration [BR]), with higher biomass (glucose-induced
      respiration [GIR]), and used a greater number of carbon sources than
      monocultures. Communities associated with deciduous tree species used a greater
      number of carbon sources than those associated with evergreen species, suggesting
      a greater soil carbon storage capacity. There were no differences in microbial
      composition (PLFA) between monocultures and SR mixtures. The FD and the CWM of
      several functional traits affected both BR and GIR. In general, the CWM of traits
      had stronger effects than did FD, suggesting that certain traits of dominant
      species have more effect on ecosystem processes than does FD. Both the functions
      of GIR and BR were positively related to aboveground tree community productivity.
      Both tree diversity (SR) and identity (species and functional identity-leaf
      habit) affected soil microbial community respiration, biomass, and composition.
      For the first time, we identified functional traits related to life-history
      strategy, as well as root traits that influence another trophic level, soil
      microbial community function, via effects on BR and GIR.

PMID- 29043049
TI  - Polyphagy and diversification in tussock moths: Support for the oscillation
      hypothesis from extreme generalists.
AB  - Theory on plasticity driving speciation, as applied to insect-plant interactions
      (the oscillation hypothesis), predicts more species in clades with higher
      diversity of host use, all else being equal. Previous support comes mainly from
      specialized herbivores such as butterflies, and plasticity theory suggests that
      there may be an upper host range limit where host diversity no longer promotes
      diversification. The tussock moths (Erebidae: Lymantriinae) are known for extreme
      levels of polyphagy. We demonstrate that this system is also very different from
      butterflies in terms of phylogenetic signal for polyphagy and for use of specific
      host orders. Yet we found support for the generality of the oscillation
      hypothesis, in that clades with higher diversity of host use were found to
      contain more species. These clades also consistently contained the most
      polyphagous single species. Comparing host use in Lymantriinae with related taxa
      shows that the taxon indeed stands out in terms of the frequency of polyphagous
      species. Comparative evidence suggests that this is most probably due to its
      nonfeeding adults, with polyphagy being part of a resulting life history
      syndrome. Our results indicate that even high levels of plasticity can drive
      diversification, at least when the levels oscillate over time.

PMID- 29043050
TI  - Prediction of biodiversity hotspots in the Anthropocene: The case of veteran
      oaks.
AB  - Over the past centuries, humans have transformed large parts of the biosphere,
      and there is a growing need to understand and predict the distribution of
      biodiversity hotspots influenced by the presence of humans. Our basic hypothesis
      is that human influence in the Anthropocene is ubiquitous, and we predict that
      biodiversity hot spot modeling can be improved by addressing three challenges
      raised by the increasing ecological influence of humans: (i) anthropogenically
      modified responses to individual ecological factors, (ii) fundamentally different
      processes and predictors in landscape types shaped by different land use
      histories and (iii) a multitude and complexity of natural and anthropogenic
      processes that may require many predictors and even multiple models in different
      landscape types. We modeled the occurrence of veteran oaks in Norway, and found,
      in accordance with our basic hypothesis and predictions, that humans influence
      the distribution of veteran oaks throughout its range, but in different ways in
      forests and open landscapes. In forests, geographical and topographic variables
      related to the oak niche are still important, but the occurrence of veteran oaks
      is shifted toward steeper slopes, where logging is difficult. In open landscapes,
      land cover variables are more important, and veteran oaks are more common toward
      the north than expected from the fundamental oak niche. In both landscape types,
      multiple predictor variables representing ecological and human-influenced
      processes were needed to build a good model, and several models performed almost
      equally well. Models accounting for the different anthropogenic influences on
      landscape structure and processes consistently performed better than models based
      exclusively on natural biogeographical and ecological predictors. Thus, our
      results for veteran oaks clearly illustrate the challenges to distribution
      modeling raised by the ubiquitous influence of humans, even in a moderately
      populated region, but also show that predictions can be improved by explicitly
      addressing these anthropogenic complexities.

PMID- 29043051
TI  - Effect of climate change on bud phenology of young aspen plants (Populus tremula.
      L).
AB  - Boreal tree species are excellent tools for studying tolerance to climate change.
      Bud phenology is a trait, which is highly sensitive to environmental fluctuations
      and thus useful for climate change investigations. However, experimental studies
      of bud phenology under simulated climate change outdoors are deficient. We
      conducted a multifactorial field experiment with single (T, UVA, UVB) and
      combined treatments (UVA+T, UVB+T) of elevated temperature (T, +2 degrees C) and
      ultraviolet-B radiation (+30% UVB) in order to examine their impact on both male
      and female genotypes of aspen (Populus tremula L.). This study focuses on the
      effect of the treatments in years 2 and 3 after planting (2013, 2014) and follows
      how bud phenology is adapting in year 4 (2015), when the treatments were
      discontinued. Moreover, the effect of bud removal was recorded. We found that
      elevated temperature played a key role in delaying bud set and forcing bud break
      in intact individuals, as well as slightly delaying bud break in bud-removed
      individuals. UVB delayed the bud break in bud-removed males. In addition, both
      UVA and UVB interacted with temperature in year 3 and even in year 4, when the
      treatments were off, but only in male individuals. Axillary bud removal forced
      both bud break and bud set under combined treatments (UVA+T, UVB+T) and delayed
      both under individual treatments (T, UVB). In conclusion, male aspens were more
      responsive to the treatments than females and that effect of elevated temperature
      and UV radiation on bud set and bud break of aspen is not disappearing over 4
      year study period.

PMID- 29043052
TI  - Evolution of a mating preference for a dual-utility trait used in intrasexual
      competition in genetically monogamous populations.
AB  - The selection pressures by which mating preferences for ornamental traits can
      evolve in genetically monogamous mating systems remain understudied. Empirical
      evidence from several taxa supports the prevalence of dual-utility traits,
      defined as traits used both as armaments in intersexual selection and ornaments
      in intrasexual selection, as well as the importance of intrasexual resource
      competition for the evolution of female ornamentation. Here, we study whether
      mating preferences for traits used in intrasexual resource competition can evolve
      under genetic monogamy. We find that a mating preference for a competitive trait
      can evolve and affect the evolution of the trait. The preference is more likely
      to persist when the fecundity benefit for mates of successful competitors is
      large and the aversion to unornamented potential mates is strong. The preference
      can persist for long periods or potentially permanently even when it incurs
      slight costs. Our results suggest that, when females use ornaments as signals in
      intrasexual resource competition, males can evolve mating preferences for those
      ornaments, illuminating both the evolution of female ornamentation and the
      evolution of male preferences for female ornaments in monogamous species.

PMID- 29043053
TI  - Ecological niche comparison and molecular phylogeny segregate the invasive moss
      species Campylopus introflexus (Leucobryaceae, Bryophyta) from its closest
      relatives.
AB  - The delimitation of the invasive moss species Campylopus introflexus from its
      closest relative, Campylopus pilifer, has been long debated based on morphology.
      Previous molecular phylogenetic reconstructions based on the nuclear ribosomal
      internal transcribed spacers (ITS) 1 and 2 showed that C. pilifer is split into
      an Old World and a New World lineage, but remained partly inconclusive concerning
      the relationships between these two clades and C. introflexus. Analyses of an
      extended ITS dataset displayed statistically supported incongruence between ITS1
      and ITS2. ITS1 separates the New World clade of C. pilifer from a clade
      comprising C. introflexus and the Old World C. pilifer. Ancestral state
      reconstruction showed that this topology is morphologically supported by
      differences in the height of the dorsal costal lamellae in leaf cross-section
      (despite some overlap). ITS2, in contrast, supports the current morphological
      species concept, i.e., separating C. introflexus from C. pilifer, which is
      morphologically supported by the orientation of the hyaline hair point at leaf
      apex as well as costal lamellae height. Re-analysis of published and newly
      generated plastid atpB-rbcL spacer sequences supported the three ITS lineages.
      Ecological niche modeling proved a useful approach and showed that all three
      molecular lineages occupy distinct environmental spaces that are similar, but
      undoubtedly not equivalent. In line with the ITS1 topology, the C. pilifer
      lineage from the New World occupies the most distinct environmental niche,
      whereas the niches of Old World C. pilifer and C. introflexus are very similar.
      Taking the inferences from ecological niche comparisons, phylogenetics, and
      morphology together, we conclude that all three molecular lineages represent
      different taxa that should be recognized as independent species, viz. C.
      introflexus, C. pilifer (Old World clade), and the reinstated C. lamellatus Mont.
      (New World clade).

PMID- 29043054
TI  - Woody structure facilitates invasion of woody plants by providing perches for
      birds.
AB  - Woody encroachment threatens prairie ecosystems globally, and thus understanding
      the mechanisms that facilitate woody encroachment is of critical importance.
      Coastal tallgrass prairies along the Gulf Coast of the US are currently
      threatened by the spread of several species of woody plants. We studied a coastal
      tallgrass prairie in Texas, USA, to determine if existing woody structure
      increased the supply of seeds from woody plants via dispersal by birds.
      Specifically, we determined if (i) more seedlings of an invasive tree (Tridacia
      sebifera) are present surrounding a native woody plant (Myrica cerifera); (ii)
      wooden perches increase the quantity of seeds dispersed to a grassland; and (iii)
      perches alter the composition of the seed rain seasonally in prairie habitats
      with differing amounts of native and invasive woody vegetation, both underneath
      and away from artificial wooden perches. More T. sebifera seedlings were found
      within M. cerifera patches than in graminoid-dominated areas. Although perches
      did not affect the total number of seeds, perches changed the composition of seed
      rain to be less dominated by grasses and forbs. Specifically, 20-30 times as many
      seeds of two invasive species of woody plants were found underneath perches
      independent of background vegetation, especially during months when seed rain was
      highest. These results suggest that existing woody structure in a grassland can
      promote further woody encroachment by enhancing seed dispersal by birds. This
      finding argues for management to reduce woody plant abundance before exotic
      plants set seeds and argues against the use of artificial perches as a
      restoration technique in grasslands threatened by woody species.

PMID- 29043055
TI  - Seasonal dynamics in mosquito abundance and temperature do not influence avian
      malaria prevalence in the Himalayan foothills.
AB  - We examined seasonal prevalence in avian haemosporidians (Plasmodium and
      Haemoproteus) in migrant and resident birds in western Himalaya, India. We
      investigated how infection with haemosporidians in avian hosts is associated with
      temporal changes in temperature and mosquito abundance along with host abundance
      and life-history traits (body mass). Using molecular methods for parasite
      detection and sequencing partial cytochrome b gene, 12 Plasmodium and 27
      Haemoproteus lineages were isolated. Our 1-year study from December 2008 to
      December 2009 in tropical Himalayan foothills revealed a lack of seasonal
      variation in Plasmodium spp. prevalence in birds despite a strong correlation
      between mosquito abundance and temperature. The probability of infection with
      Plasmodium decreased with increase in temperature. Total parasite prevalence and
      specifically Plasmodium prevalence showed an increase with average avian body
      mass. In addition, total prevalence exhibited a U-shaped relationship with avian
      host abundance. There was no difference in prevalence of Plasmodium spp. or
      Haemoproteus spp. across altitudes; parasite prevalence in high-altitude
      locations was mainly driven by the seasonal migrants. One Haemoproteus lineage
      showed cross-species infections between migrant and resident birds. This is the
      first molecular study in the tropical Himalayan bird community that emphasizes
      the importance of studying seasonal variation in parasite prevalence. Our study
      provides a basis for further evolutionary study on the epidemiology of avian
      malaria and spread of disease across Himalayan bird communities, which may not
      have been exposed to vectors and parasites throughout the year, with
      consequential implications to the risk of infection to naive resident birds in
      high altitude.

PMID- 29043056
TI  - Genotype by sequencing identifies natural selection as a driver of intraspecific
      divergence in Atlantic populations of the high dispersal marine invertebrate,
      Macoma petalum.
AB  - Mitochondrial DNA analyses indicate that the Bay of Fundy population of the
      intertidal tellinid bivalve Macoma petalum is genetically divergent from coastal
      populations in the Gulf of Maine and Nova Scotia. To further examine the
      evolutionary forces driving this genetic break, we performed double digest
      genotype by sequencing (GBS) to survey the nuclear genome for evidence of both
      neutral and selective processes shaping this pattern. The resulting reads were
      mapped to a partial transcriptome of its sister species, M. balthica, to identify
      single nucleotide polymorphisms (SNPs) in protein-coding genes. Population
      assignment tests, principle components analyses, analysis of molecular variance,
      and outlier tests all support differentiation between the Bay of Fundy genotype
      and the genotypes of the Gulf of Maine, Gulf of St. Lawrence, and Nova Scotia.
      Although both neutral and non-neutral patterns of genetic subdivision were
      significant, genetic structure among the regions was nearly 20 times higher for
      loci putatively under selection, suggesting a strong role for natural selection
      as a driver of genetic diversity in this species. Genetic differences were the
      greatest between the Bay of Fundy and all other population samples, and some
      outlier proteins were involved in immunity-related processes. Our results suggest
      that in combination with limited gene flow across the mouth of the Bay of Fundy,
      local adaptation is an important driver of intraspecific genetic variation in
      this marine species with high dispersal potential.

PMID- 29043057
TI  - Flower resource and land management drives hoverfly communities and bee abundance
      in seminatural and agricultural grasslands.
AB  - Pollination is a key ecosystem service, and appropriate management, particularly
      in agricultural systems, is essential to maintain a diversity of pollinator
      guilds. However, management recommendations frequently focus on maintaining plant
      communities, with the assumption that associated invertebrate populations will be
      sustained. We tested whether plant community, flower resources, and soil moisture
      would influence hoverfly (Syrphidae) abundance and species richness in
      floristically-rich seminatural and floristically impoverished agricultural
      grassland communities in Wales (U.K.) and compared these to two Hymenoptera
      genera, Bombus, and Lasioglossum. Interactions between environmental variables
      were tested using generalized linear modeling, and hoverfly community composition
      examined using canonical correspondence analysis. There was no difference in
      hoverfly abundance, species richness, or bee abundance, between grassland types.
      There was a positive association between hoverfly abundance, species richness,
      and flower abundance in unimproved grasslands. However, this was not evident in
      agriculturally improved grassland, possibly reflecting intrinsically low flower
      resource in these habitats, or the presence of plant species with low or
      relatively inaccessible nectar resources. There was no association between soil
      moisture content and hoverfly abundance or species richness. Hoverfly community
      composition was influenced by agricultural improvement and the amount of flower
      resource. Hoverfly species with semiaquatic larvae were associated with both
      seminatural and agricultural wet grasslands, possibly because of localized larval
      habitat. Despite the absence of differences in hoverfly abundance and species
      richness, distinct hoverfly communities are associated with marshy grasslands,
      agriculturally improved marshy grasslands, and unimproved dry grasslands, but not
      with improved dry grasslands. Grassland plant community cannot be used as a proxy
      for pollinator community. Management of grasslands should aim to maximize the
      pollinator feeding resource, as well as maintain plant communities. Retaining
      waterlogged ground may enhance the number of hoverflies with semiaquatic larvae.

PMID- 29043058
TI  - Closely related octopus species show different spatial genetic structures in
      response to the Antarctic seascape.
AB  - Determining whether comparable processes drive genetic divergence among marine
      species is relevant to molecular ecologists and managers alike. Sympatric species
      with similar life histories might be expected to show comparable patterns of
      genetic differentiation and a consistent influence of environmental factors in
      shaping divergence. We used microsatellite loci to quantify genetic
      differentiation across the Scotia Arc in three species of closely related benthic
      octopods, Pareledone turqueti, P. charcoti, and Adelieledone polymorpha. The
      relative importance of environmental factors (latitude, longitude, depth, and
      temperature) in shaping genetic structure was investigated when significant
      spatial genetic structure was uncovered. Isolated populations of P. turqueti and
      A. polymorpha at these species' range margins were genetically different to
      samples close to mainland Antarctica; however, these species showed different
      genetic structures at a regional scale. Samples of P. turqueti from the Antarctic
      Peninsula, Elephant Island, and Signy Island were genetically different, and this
      divergence was associated primarily with sample collection depth. By contrast,
      weak or nonsignificant spatial genetic structure was evident across the Antarctic
      Peninsula, Elephant Island, and Signy Island region for A. polymorpha, and slight
      associations between population divergence and temperature or depth (and/or
      longitude) were detected. Pareledone charcoti has a limited geographic range, but
      exhibited no genetic differentiation between samples from a small region of the
      Scotia Arc (Elephant Island and the Antarctic Peninsula). Thus, closely related
      species with similar life history strategies can display contrasting patterns of
      genetic differentiation depending on spatial scale; moreover, depth may drive
      genetic divergence in Southern Ocean benthos.

PMID- 29043059
TI  - Thermal plasticity in postembryonic life history traits of a widely distributed
      Collembola: Effects of macroclimate and microhabitat on genotypic differences.
AB  - Life history traits in many ectotherms show complex patterns of variation among
      conspecific populations sampled along wide latitudinal or climatic gradients.
      However, few studies have assessed whether these patterns can be explained better
      by thermal reaction norms of multiple life history traits, covering major aspects
      of the life cycle. In this study, we compared five populations of a Holarctic,
      numerically dominant soil microarthropod species, Folsomia quadrioculata, sampled
      from a wide latitudinal gradient (56-81 degrees N), for growth, development,
      fecundity, and survival across four temperatures (10, 15, 20, and 25 degrees C)
      in common garden experiments. We evaluated the extent to which macroclimate could
      explain differences in thermal adaptation and life history strategies among
      populations. The common garden experiments revealed large genotypic differences
      among populations in all the traits, which were little explained by latitude and
      macroclimate. In addition, the life history strategies (traits combined) hardly
      revealed any systematic difference related to latitude and macroclimate. The
      overall performance of the northernmost population from the most stochastic
      microclimate and the southernmost population, which remains active throughout the
      year, was least sensitive to the temperature treatments. In contrast, performance
      of the population from the most predictable microclimate peaked within a narrow
      temperature range (around 15 degrees C). Our findings revealed limited support
      for macroclimate-based predictions, and indicated that local soil habitat
      conditions related to predictability and seasonality might have considerable
      influence on the evolution of life history strategies of F. quadrioculata. This
      study highlights the need to combine knowledge on microhabitat characteristics,
      and demography, with findings from common garden experiments, for identifying the
      key drivers of life history evolution across large spatial scales, and wide
      climate gradients. We believe that similar approaches may substantially improve
      the understanding of adaptation in many terrestrial ectotherms with low dispersal
      ability.

PMID- 29043061
TI  - Refining the cheatgrass-fire cycle in the Great Basin: Precipitation timing and
      fine fuel composition predict wildfire trends.
AB  - Larger, more frequent wildfires in arid and semi-arid ecosystems have been
      associated with invasion by non-native annual grasses, yet a complete
      understanding of fine fuel development and subsequent wildfire trends is lacking.
      We investigated the complex relationships among weather, fine fuels, and fire in
      the Great Basin, USA. We first modeled the annual and time-lagged effects of
      precipitation and temperature on herbaceous vegetation cover and litter
      accumulation over a 26-year period in the northern Great Basin. We then modeled
      how these fine fuels and weather patterns influence subsequent wildfires. We
      found that cheatgrass cover increased in years with higher precipitation and
      especially when one of the previous 3 years also was particularly wet. Cover of
      non-native forbs and native herbs also increased in wet years, but only after
      several dry years. The area burned by wildfire in a given year was mostly
      associated with native herb and non-native forb cover, whereas cheatgrass mainly
      influenced area burned in the form of litter derived from previous years' growth.
      Consequently, multiyear weather patterns, including precipitation in the previous
      1-3 years, was a strong predictor of wildfire in a given year because of the time
      needed to develop these fine fuel loads. The strong relationship between
      precipitation and wildfire allowed us to expand our inference to 10,162 wildfires
      across the entire Great Basin over a 35-year period from 1980 to 2014. Our
      results suggest that the region's precipitation pattern of consecutive wet years
      followed by consecutive dry years results in a cycle of fuel accumulation
      followed by weather conditions that increase the probability of wildfire events
      in the year when the cycle transitions from wet to dry. These patterns varied
      regionally but were strong enough to allow us to model annual wildfire risk
      across the Great Basin based on precipitation alone.

PMID- 29043060
TI  - Origins of the Greenland shark (Somniosus microcephalus): Impacts of ice-olation
      and introgression.
AB  - Herein, we use genetic data from 277 sleeper sharks to perform coalescent-based
      modeling to test the hypothesis of early Quaternary emergence of the Greenland
      shark (Somniosus microcephalus) from ancestral sleeper sharks in the Canadian
      Arctic-Subarctic region. Our results show that morphologically cryptic somniosids
      S. microcephalus and Somniosus pacificus can be genetically distinguished using
      combined mitochondrial and nuclear DNA markers. Our data confirm the presence of
      genetically admixed individuals in the Canadian Arctic and sub-Arctic, and
      temperate Eastern Atlantic regions, suggesting introgressive hybridization upon
      secondary contact following the initial species divergence. Conservative
      substitution rates fitted to an Isolation with Migration (IM) model indicate a
      likely species divergence time of 2.34 Ma, using the mitochondrial sequence DNA,
      which in conjunction with the geographic distribution of admixtures and Pacific
      signatures likely indicates speciation associated with processes other than the
      closing of the Isthmus of Panama. This time span coincides with further planetary
      cooling in the early Quaternary period followed by the onset of oscillating
      glacial-interglacial cycles. We propose that the initial S. microcephalus-S.
      pacificus split, and subsequent hybridization events, were likely associated with
      the onset of Pleistocene glacial oscillations, whereby fluctuating sea levels
      constrained connectivity among Arctic oceanic basins, Arctic marginal seas, and
      the North Atlantic Ocean. Our data demonstrates support for the evolutionary
      consequences of oscillatory vicariance via transient oceanic isolation with
      subsequent secondary contact associated with fluctuating sea levels throughout
      the Quaternary period-which may serve as a model for the origins of Arctic marine
      fauna on a broad taxonomic scale.

PMID- 29043063
TI  - A survey of working conditions within biomedical research in the United Kingdom.
AB  - Background: Many recent articles have presented a bleak view of career prospects
      in biomedical research in the US. Too many PhDs and postdocs are trained for too
      few research positions, creating a "holding-tank" of experienced senior postdocs
      who are unable to get a permanent position. Coupled with relatively low salaries
      and the high levels of pressure to publish in top-tier academic journals, this
      has created a toxic environment that is perhaps responsible for a recently
      observed decline in biomedical postdocs in the US, the so-called "postdocalypse".
      Methods: In order to address the gulf of information relating to working habits
      and attitudes of UK-based biomedical researchers, a survey was conducted and
      analysed to examine discrete profiles for three major career stages: the PhD, the
      postdoc and the principal investigator. Results: Overall, the data presented here
      echoes trends observed in the US: Scientists in the UK feel disillusioned with
      academic research, due to the low chance of getting a permanent position and the
      long hours required at the bench. Also like the US, large numbers of researchers
      at each distinct career stage are considering leaving biomedical research
      altogether. Conclusions: There are several systemic flaws in the academic
      scientific research machine - for example to continual overproduction of PhDs and
      the lack of stability in the early-mid stages of a research career - that are
      slowly being addressed in countries such as the US and Germany. This data
      suggests that similar flaws also exist in the UK, with a large proportion of
      respondents concerned about their future in research. To avoid lasting damage to
      the biomedical research agenda in the UK, addressing such concerns should be a
      major priority.

PMID- 29043062
TI  - The future of metabolomics in ELIXIR.
AB  - Metabolomics, the youngest of the major omics technologies, is supported by an
      active community of researchers and infrastructure developers across Europe. To
      coordinate and focus efforts around infrastructure building for metabolomics
      within Europe, a workshop on the "Future of metabolomics in ELIXIR" was organised
      at Frankfurt Airport in Germany. This one-day strategic workshop involved
      representatives of ELIXIR Nodes, members of the PhenoMeNal consortium developing
      an e-infrastructure that supports workflow-based metabolomics analysis pipelines,
      and experts from the international metabolomics community. The workshop
      established metabolite identification as the critical area, where a maximal
      impact of computational metabolomics and data management on other fields could be
      achieved. In particular, the existing four ELIXIR Use Cases, where the
      metabolomics community - both industry and academia - would benefit most, and
      which could be exhaustively mapped onto the current five ELIXIR Platforms were
      discussed. This opinion article is a call for support for a new ELIXIR
      metabolomics Use Case, which aligns with and complements the existing and planned
      ELIXIR Platforms and Use Cases.

PMID- 29034075
TI  - Structural brain abnormalities in 12 persons with aniridia.
AB  - Background: Aniridia is a disorder predominately caused by heterozygous loss-of
      function mutations of the PAX6 gene, which is a transcriptional regulator
      necessary for normal eye and brain development.  The ocular abnormalities of
      aniridia have been well characterized, but mounting evidence has implicated brain
      related phenotypes as a prominent feature of this disorder as well. 
      Investigations using neuroimaging in aniridia patients have shown reductions in
      discrete brain structures and changes in global grey and white matter.  However,
      limited sample sizes and substantive heterogeneity of structural phenotypes in
      the brain remain a challenge.  Methods: Here, we examined brain structure in a
      new population sample in an effort to add to the collective understanding of
      anatomical abnormalities in aniridia.  The current study used 3T magnetic
      resonance imaging to acquire high-resolution structural data in 12 persons with
      aniridia and 12 healthy demographically matched comparison subjects.  Results: We
      examined five major structures: the anterior commissure, the posterior
      commissure, the pineal gland, the corpus callosum, and the optic chiasm.  The
      most consistent reductions were found in the anterior commissure and the pineal
      gland; however, abnormalities in all of the other structures examined were
      present in at least one individual.  Conclusions: Our results indicate that the
      anatomical abnormalities in aniridia are variable and largely individual
      specific.  These findings suggest that future studies investigate this
      heterogeneity further, and that normal population variation should be considered
      when evaluating structural abnormalities.

PMID- 29043065
TI  - CNS cell-type localization and LPS response of TLR signaling pathways.
AB  - Background: Innate immune signaling in the brain has emerged as a contributor to
      many central nervous system (CNS) pathologies, including mood disorders,
      neurodegenerative disorders, neurodevelopmental disorders, and addiction. Toll
      like receptors (TLRs), a key component of the innate immune response, are
      particularly implicated in neuroimmune dysfunction. However, most of our
      understanding about TLR signaling comes from the peripheral immune response, and
      it is becoming clear that the CNS immune response is unique. One controversial
      aspect of neuroimmune signaling is which CNS cell types are involved. While
      microglia are the CNS cell-type derived from a myeloid lineage, studies suggest
      that other glial cell types and even neurons express TLRs, although this idea is
      controversial. Furthermore, recent work suggests a discrepancy between RNA and
      protein expression within the CNS. Methods: To elucidate the CNS cell-type
      localization of TLRs and their downstream signaling molecules, we isolated
      microglia and astrocytes from the brain of adult mice treated with saline or the
      TLR4 ligand lipopolysaccharide (LPS). Glial mRNA and protein expression was
      compared to a cellular-admixture to determine cell-type enrichment. Results:
      Enrichment analysis revealed that most of the TLR pathway genes are localized in
      microglia and changed in microglia following immune challenge. However,
      expression of Tlr3 was enriched in astrocytes, where it increased in response to
      LPS. Furthermore, attempts to determine protein cell-type localization revealed
      that many antibodies are non-specific and that antibody differences are
      contributing to conflicting localization results. Conclusions: Together these
      results highlight the cell types that should be looked at when studying TLR
      signaling gene expression and suggest that non-antibody approaches need to be
      used to accurately evaluate protein expression.

PMID- 29034080
TI  - Professional medical writing support and the reporting quality of randomized
      controlled trial abstracts among high-impact general medical journals.
AB  - Background: In articles reporting randomized controlled trials, professional
      medical writing support is associated with increased adherence to Consolidated
      Standards of Reporting Trials (CONSORT). We set out to determine whether
      professional medical writing support was also associated with improved adherence
      to CONSORT for Abstracts. Methods: Using data from a previously published cross
      sectional study of 463 articles reporting randomized controlled trials published
      between 2011 and 2014 in five top medical journals, we determined the association
      between professional medical writing support and CONSORT for Abstracts items
      using a Wilcoxon rank-sum test. Results: The mean proportion of adherence to
      CONSORT for Abstracts items reported was similar with and without professional
      medical writing support (64.3% vs 66.5%, respectively; p=0.30). Professional
      medical writing support was associated with lower adherence to reporting study
      setting (relative risk [RR]; 0.40; 95% confidence interval [CI], 0.23-0.70), and
      higher adherence to disclosing harms/side effects (RR 2.04; 95% CI, 1.37-3.03)
      and funding source (RR 1.75; 95% CI, 1.18-2.60). Conclusions: Although
      professional medical writing support was not associated with increased overall
      adherence to CONSORT for Abstracts, important aspects were improved with
      professional medical writing support, including reporting of adverse events and
      funding source. This study identifies areas to consider for improvement.

PMID- 29043067
TI  - recount workflow: Accessing over 70,000 human RNA-seq samples with Bioconductor.
AB  - The recount2 resource is composed of over 70,000 uniformly processed human RNA
      seq samples spanning TCGA and SRA, including GTEx. The processed data can be
      accessed via the recount2 website and the recount Bioconductor package. This
      workflow explains in detail how to use the recount package and how to integrate
      it with other Bioconductor packages for several analyses that can be carried out
      with the recount2 resource. In particular, we describe how the coverage count
      matrices were computed in recount2 as well as different ways of obtaining public
      metadata, which can facilitate downstream analyses. Step-by-step directions show
      how to do a gene-level differential expression analysis, visualize base-level
      genome coverage data, and perform an analyses at multiple feature levels. This
      workflow thus provides further information to understand the data in recount2 and
      a compendium of R code to use the data.

PMID- 29043069
TI  - Recent advances in the understanding and management of Klebsiella pneumoniae.
AB  - Klebsiella pneumoniae, a gram-negative bacillus of the Enterobacteriaceae family,
      is a component of the normal human microbiota and a common cause of community-
      and healthcare-associated infections. The increasing prevalence of antimicrobial
      resistance among K. pneumoniae isolates, particularly among those causing
      healthcare-associated infections, is an important public health concern.
      Infections caused by these multidrug-resistant organisms, for which safe and
      effective antimicrobial therapy options are extremely limited, are associated
      with poor outcomes for patients. The optimal approach to the treatment of
      infections caused by these multidrug-resistant strains remains undefined, and
      treatment decisions for an individual patient should be based on a number of
      organism- (for example, minimum inhibitory concentration) and patient-specific
      (for example, site of infection) factors. The emergence of pandrug-resistant
      strains of K. pneumoniae highlights the critical need for consistent
      implementation of effective strategies for prevention of transmission and
      infection and for the development of new antimicrobials with activity against
      these emerging pathogens.

PMID- 29043068
TI  - Meta-fibrosis links positive energy balance and mitochondrial metabolism to
      insulin resistance.
AB  - Obesity and insulin resistance often emerge from positive energy balance and
      generally are linked to low-grade inflammation. This low-grade inflammation has
      been called "meta-inflammation" because it is a consequence of the metabolic
      dysregulation that can accompany overnutrition. One means by which meta
      inflammation is linked to insulin resistance is extracellular matrix expansion
      secondary to meta-inflammation, which we define here as "meta-fibrosis". The
      significance of meta-fibrosis is that it reflects a situation in which the
      extracellular matrix functions as a multi-level integrator of local (for example,
      mitochondrial reactive oxygen species production) and systemic (for example,
      inflammation) inputs that couple to cellular processes creating insulin
      resistance. While adipose tissue extracellular matrix remodeling has received
      considerable attention, it is becoming increasingly apparent that liver and
      skeletal muscle extracellular matrix remodeling also contributes to insulin
      resistance. In this review, we address recent advances in our understanding of
      energy balance, mitochondrial energetics, meta-inflammation, and meta-fibrosis in
      the development of insulin resistance.

PMID- 29043070
TI  - Bacterial vaginosis.
AB  - Bacterial vaginosis is the most prevalent cause of abnormal vaginal discharge in
      women of childbearing age. It can have a major impact on quality of life and
      psychological wellbeing if frequently recurrent and strongly symptomatic. The use
      of molecular techniques to study the vaginal microbiome is increasing our
      understanding of the dynamic changes in flora that occur in health and disease.
      It might soon be possible to separate Gardnerella into different pathogenic and
      non-pathogenic species. Many groups are studying compounds that can disrupt the
      biofilm which is dominated by Gardnerella and Atopobium vaginae. Several studies
      in the last decade support the concept of bacterial vaginosis as a sexually
      transmitted infection.

PMID- 29043072
TI  - Expanding the chemical information science gateway.
AB  - Broadly defined, chemical information science (CIS) covers chemical structure and
      data analysis including biological activity data as well as processing,
      organization, and retrieval of any form of chemical information. The CIS Gateway
      (CISG) of F1000Research was created to communicate research involving the entire
      spectrum of chemical information, including chem(o)informatics. CISG provides a
      forum for high-quality publications and a meaningful alternative to conventional
      journals. This gateway is supported by leading experts in the field recognizing
      the need for open science and a flexible publication platform enabling off-the
      beaten path contributions. This editorial aims to further rationalize the scope
      of CISG, position it within its scientific environment, and open it up to a wider
      audience. Chemical information science is an interdisciplinary field with high
      potential to interface with experimental work.

PMID- 29043071
TI  - Recent advances in the management of peptic ulcer bleeding.
AB  - Acute upper gastrointestinal haemorrhage due to peptic ulcer bleeding remains an
      important cause of emergency presentation and hospital admission. Despite
      advances in many aspects of management, peptic ulcer bleeding is still associated
      with significant morbidity, mortality, and healthcare costs. Comprehensive
      international guidelines have been published, but advances as well as
      controversies continue to evolve. Important recent advances include the evidence
      supporting a more restrictive transfusion strategy aiming for a target
      haemoglobin of 70-90 g/l. Comparative studies have confirmed that the Glasgow
      Blatchford score remains the most useful score for predicting the need for
      intervention as well as for identifying the lowest-risk patients suitable for
      outpatient management. New scores, including the AIMS65 and Progetto Nazionale
      Emorragia Digestiva score, may be more accurate in predicting mortality. Pre
      endoscopy erythromycin appears to improve outcomes and is probably underused.
      High-dose oral proton pump inhibition (PPI) for 11 days after PPI infusion is
      advantageous in those with a Rockall score of 6 or more. Oral is as effective as
      parenteral iron at restoring haemoglobin levels after a peptic ulcer bleed and
      both are superior to placebo in this respect. Within endoscopic techniques,
      haemostatic powders and over-the-scope clips can be used when other methods have
      failed. A disposable Doppler probe appears to provide more accurate determination
      of both rebleeding risk and the success of endoscopic therapy than purely visual
      guidance. Non- Helicobacter pylori, non-aspirin/non-steroidal anti-inflammatory
      drug ulcers contribute an increasing percentage of bleeding peptic ulcers and are
      associated with a poor prognosis and high rebleeding rate. The optimal management
      of these ulcers remains to be determined.

PMID- 29043073
TI  - Predator and prey functional traits: understanding the adaptive machinery driving
      predator-prey interactions.
AB  - Predator-prey relationships are a central component of community dynamics.
      Classic approaches have tried to understand and predict these relationships in
      terms of consumptive interactions between predator and prey species, but
      characterizing the interaction this way is insufficient to predict the complexity
      and context dependency inherent in predator-prey relationships. Recent approaches
      have begun to explore predator-prey relationships in terms of an evolutionary
      ecological game in which predator and prey adapt to each other through reciprocal
      interactions involving context-dependent expression of functional traits that
      influence their biomechanics. Functional traits are defined as any morphological,
      behavioral, or physiological trait of an organism associated with a biotic
      interaction. Such traits include predator and prey body size, predator and prey
      personality, predator hunting mode, prey mobility, prey anti-predator behavior,
      and prey physiological stress. Here, I discuss recent advances in this functional
      trait approach. Evidence shows that the nature and strength of many interactions
      are dependent upon the relative magnitude of predator and prey functional traits.
      Moreover, trait responses can be triggered by non-consumptive predator-prey
      interactions elicited by responses of prey to risk of predation. These
      interactions in turn can have dynamic feedbacks that can change the context of
      the predator-prey interaction, causing predator and prey to adapt their traits
      through phenotypically plastic or rapid evolutionary responses-and the nature of
      their interaction. Research shows that examining predator-prey interactions
      through the lens of an adaptive evolutionary-ecological game offers a foundation
      to explain variety in the nature and strength of predator-prey interactions
      observed in different ecological contexts.

PMID- 29043074
TI  - Recent advances in eosinophilic esophagitis.
AB  - Eosinophilic esophagitis is a chronic, antigen-driven, eosinophil-predominant
      inflammatory disease of the esophagus and affects both children and adults.
      Cutting-edge technologies, such as genome-wide association studies, have advanced
      our understanding of the disease pathogenesis at a remarkable rate. Recent
      insights from genetic and mechanistic studies have concluded that a complex
      interplay between genetic and environmental risk factors, allergic sensitization,
      and esophageal-specific pathways leads to disease pathogenesis. Importantly,
      recent epidemiologic studies have found that the incidence and prevalence of
      eosinophilic esophagitis continue to rise. New guidelines have advocated the
      elimination of the term proton pump inhibitor (PPI)-responsive esophageal
      eosinophilia and have recommended using PPIs as a first-line treatment modality.
      Systemic reviews and meta-analyses confirm the efficacy of PPIs, topical
      corticosteroids, and empiric food elimination diets. Unmet needs include the
      development of birth cohort studies, validated diagnostic scoring systems,
      minimally invasive disease-monitoring methods, and the development of new
      therapies.

PMID- 29043075
TI  - Recent advances in understanding autoimmune thyroid disease: the tallest tree in
      the forest of polyautoimmunity.
AB  - Autoimmune thyroid disease (AITD) is often observed together with other
      autoimmune diseases. The coexistence of two or more autoimmune diseases in the
      same patient is referred to as polyautoimmunity, and AITD is the autoimmune
      disease most frequently involved. The occurrence of polyautoimmunity has led to
      the hypothesis that the affected patients suffer from a generalized dysregulation
      of their immune system. The present review summarizes recent discoveries
      unravelling the immunological mechanisms involved in autoimmunity, ranging from
      natural autoimmunity to disease-specific autoimmunity. Furthermore, the clinical
      grounds for considering AITD in a setting of polyautoimmunity are explored. A
      better understanding of these may pave the way for designing new treatment
      modalities targeting the underlying immune dysregulation when AITD appears in the
      context of polyautoimmunity.

PMID- 29043076
TI  - The management of functional dyspepsia in clinical practice: what lessons can be
      learnt from recent literature?
AB  - Functional dyspepsia is a prevalent functional gastrointestinal disorder that can
      significantly erode the quality of life of sufferers and places a major cost
      burden on healthcare services. In this article, we review the recent literature,
      selecting the information we consider relevant since it has changed our clinical
      management of patients with functional dyspepsia.

PMID- 29043077
TI  - Recent Advances in Understanding Werner Syndrome.
AB  - Aging, the universal phenomenon, affects human health and is the primary risk
      factor for major disease pathologies. Progeroid diseases, which mimic aging at an
      accelerated rate, have provided cues in understanding the hallmarks of aging.
      Mutations in DNA repair genes as well as in telomerase subunits are known to
      cause progeroid syndromes. Werner syndrome (WS), which is characterized by
      accelerated aging, is an autosomal-recessive genetic disorder. Hallmarks that
      define the aging process include genomic instability, telomere attrition,
      epigenetic alterations, loss of proteostasis, deregulation of nutrient sensing,
      mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered
      intercellular communication. WS recapitulates these hallmarks of aging and shows
      increased incidence and early onset of specific cancers. Genome integrity and
      stability ensure the normal functioning of the cell and are mainly guarded by the
      DNA repair machinery and telomeres. WRN, being a RecQ helicase, protects genome
      stability by regulating DNA repair pathways and telomeres. Recent advances in WS
      research have elucidated WRN's role in DNA repair pathway choice regulation,
      telomere maintenance, resolution of complex DNA structures, epigenetic
      regulation, and stem cell maintenance.

PMID- 29043078
TI  - A GAP that Divides.
AB  - Cytokinesis in metazoan cells is mediated by an actomyosin-based contractile ring
      that assembles in response to activation of the small GTPase RhoA. The guanine
      nucleotide exchange factor that activates RhoA during cytokinesis, ECT-2, is
      highly regulated. In most metazoan cells, with the notable exception of the early
      Caenorhabditis elegans embryo, RhoA activation and furrow ingression require the
      centralspindlin complex. This exception is due to the existence of a parallel
      pathway for RhoA activation in C. elegans. Centralspindlin contains CYK-4 which
      contains a predicted Rho family GTPase-activating protein (GAP) domain. The
      function of this domain has been the subject of considerable debate. Some
      publications suggest that the GAP domain promotes RhoA activation (for example,
      Zhang and Glotzer, 2015; Loria, Longhini and Glotzer, 2012), whereas others
      suggest that it functions to inactivate the GTPase Rac1 (for example, Zhuravlev
      et al., 2017). Here, we review the mechanisms underlying RhoA activation during
      cytokinesis, primarily focusing on data in C. elegans. We highlight the
      importance of considering the parallel pathway for RhoA activation and detailed
      analyses of  cyk-4 mutant phenotypes when evaluating the role of the GAP domain
      of CYK-4.

PMID- 29043079
TI  - Acute Coronary Syndromes in the Elderly.
AB  - The clinical evidence for treatment of acute coronary syndrome (ACS) in the
      elderly is less robust than in patients younger than 75 years. The elderly have
      the highest incidence of cardiovascular disease and frequently present with ACS.
      This number can be expected to increase over time because society is aging. Older
      adults often sustain unfavorable outcomes from ACS because of atypical
      presentation and delay in recognition. In addition, elderly patients commonly do
      not receive optimal guideline-directed ACS treatment. Owing to their high
      baseline risk of ischemic complications, the elderly also fare worse even with
      optimal ACS treatment as they frequently have more complex coronary disease, more
      comorbidities, less cardiovascular reserve, and a higher risk of treatment
      complications. They are also subjected to a broader range of pharmacologic
      treatment. Treatment complications can be mitigated to some extent by meticulous
      dose adjustment of antithrombotic and adjunctive therapies. While careful
      transitions of care and appropriate utilization of post-discharge secondary
      preventive measures are important in ACS patients of all ages, the elderly are
      more vulnerable to system errors and thus deserve special attention from the
      clinician.

PMID- 29043080
TI  - Recent advances in rhythm control for atrial fibrillation.
AB  - Atrial fibrillation (AF) remains a difficult management problem. The restoration
      and maintenance of sinus rhythm-rhythm control therapy-can markedly improve
      symptoms and haemodynamics for patients who have paroxysmal or persistent AF, but
      some patients fare well with rate control alone. Sinus rhythm can be achieved
      with anti-arrhythmic drugs or electrical cardioversion, but the maintenance of
      sinus rhythm without recurrence is more challenging. Catheter ablation of the AF
      triggers is more effective than anti-arrhythmic drugs at maintaining sinus
      rhythm. Whilst pulmonary vein isolation is an effective strategy, other ablation
      targets are being evaluated to improve sinus rhythm maintenance, especially in
      patients with chronic forms of AF. Previously extensive ablation strategies have
      been used for patients with persistent AF, but a recent trial has shown that
      pulmonary vein isolation without additional ablation lesions is associated with
      outcomes similar to those of more extensive ablation. This has led to an increase
      in catheter-based technology to achieve durable pulmonary vein isolation.
      Furthermore, a combination of anti-arrhythmic drugs and catheter ablation seems
      useful to improve the effectiveness of rhythm control therapy. Two large ongoing
      trials evaluate whether a modern rhythm control therapy can improve prognosis in
      patients with AF.

PMID- 29043082
TI  - Effect of sex and age on traumatic brain injury: a geographical comparative
      study.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a much researched topic in medical
      health, which requires additional studies to understand various effects of
      demographic and geographic factors that can assist in developing the most
      effective treatments. Thousands of people of different ages are suffering from
      lifelong disabilities, either mild or severe, from TBI and the number is
      increasing. This study aims to increase our understanding of the effect of sex
      and age by applying five different statistical methods to evaluate the effect of
      these covariates on two independent TBI data sets representing patients from
      different geographical cohorts. A primary data was collected from Bangladesh and
      it was compared with CRASH (Corticosteroid Randomisation after Significant Head
      Injury) data, representing various countries around the world. METHODS: The
      outcome variable for TBI considered in this paper is Glasgow Outcome Scale, which
      is a four point scale. It was converted to a binary outcome scale for fitting of
      Fisher's exact test, a test of proportions and a binary linear model. For
      analyzing ordinal outcomes, the proportional odds model and the sliding dichotomy
      model were fitted. As the sample size of the Bangladeshi data set was small,
      parametric bootstrapping was applied for the consistency of results. RESULTS:
      Females were the worse sufferers of TBI compared to men, according to CRASH data
      set. The old (aged above 58 years) followed by adults (age 25 to 58) were the
      most vulnerable victims. Interaction effects concluded that old women tended to
      endure the worst outcomes of TBI. This conclusion came from the CRASH data set
      representing the world in general, whereas such effects were not present in the
      Bangladesh data set. Additional application of parametric bootstrapping for the
      smaller Bangladesh data set did not result into any significant outcome.
      CONCLUSION: The effect of gender and age could be stronger in some countries than
      others which is driving the significance in CRASH and was not found in
      Bangladesh. It reflects the necessity of incorporating geographic patterns as
      well as demographic features of patients while developing treatments and
      designing clinical trials.

PMID- 29043081
TI  - Effects of phospho- and calciotropic hormones on electrolyte transport in the
      proximal tubule.
AB  - Calcium and phosphate are critical for a myriad of physiological and cellular
      processes within the organism. Consequently, plasma levels of calcium and
      phosphate are tightly regulated. This occurs through the combined effects of the
      phospho- and calciotropic hormones, parathyroid hormone (PTH), active vitamin D
      3, and fibroblast growth factor 23 (FGF23). The organs central to this are the
      kidneys, intestine, and bone. In the kidney, the proximal tubule reabsorbs the
      majority of filtered calcium and phosphate, which amounts to more than 60% and
      90%, respectively. The basic molecular mechanisms responsible for phosphate
      reclamation are well described, and emerging work is delineating the molecular
      identity of the paracellular shunt wherein calcium permeates the proximal tubular
      epithelium. Significant experimental work has delineated the molecular effects of
      PTH and FGF23 on these processes as well as their regulation of active vitamin D
      3 synthesis in this nephron segment. The integrative effects of both phospho- and
      calciotropic hormones on proximal tubular solute transport and subsequently whole
      body calcium-phosphate balance thus have been further complicated. Here, we first
      review the molecular mechanisms of calcium and phosphate reabsorption from the
      proximal tubule and how they are influenced by the phospho- and calciotropic
      hormones acting on this segment and then consider the implications on both renal
      calcium and phosphate handling as well as whole body mineral balance.

PMID- 29043083
TI  - A framework for continuous target tracking during MR-guided high intensity
      focused ultrasound thermal ablations in the abdomen.
AB  - BACKGROUND: During lengthy magnetic resonance-guided high intensity focused
      ultrasound (MRg-HIFU) thermal ablations in abdominal organs, the therapeutic work
      flow is frequently hampered by various types of physiological motion occurring at
      different time-scales. If left un-addressed this can lead to an incomplete
      therapy and/or to tissue damage of organs-at-risk. While previous studies focus
      on correction schemes for displacements occurring at a particular time-scale
      within the work-flow of an MRg-HIFU therapy, in the current work we propose a
      motion correction strategy encompassing the entire work-flow. METHODS: The
      proposed motion compensation framework consists of several linked components,
      each being adapted to motion occurring at a particular time-scale. While
      respiration was addressed through a fast correction scheme, long term organ
      drifts were compensated using a strategy operating on time-scales of several
      minutes. The framework relies on a periodic examination of the treated area via
      MR scans which are then registered to a reference scan acquired at the beginning
      of the therapy. The resulting displacements were used for both on-the-fly re
      optimization of the interventional plan and to ensure the spatial fidelity
      between the different steps of the therapeutic work-flow. The approach was
      validated in three complementary studies: an experiment conducted on a phantom
      undergoing a known motion pattern, a study performed on the abdomen of 10 healthy
      volunteers and during 3 in-vivo MRg-HIFU ablations on porcine liver. RESULTS:
      Results have shown that, during lengthy MRg-HIFU thermal therapies, the human
      liver and kidney can manifest displacements that exceed acceptable therapeutic
      margins. Also, it was demonstrated that the proposed framework is capable of
      providing motion estimates with sub-voxel precision and accuracy. Finally, the 3
      successful animal studies demonstrate the compatibility of the proposed approach
      with the work-flow of an MRg-HIFU intervention under clinical conditions.
      CONCLUSIONS: In the current study we proposed an image-based motion compensation
      framework dedicated to MRg-HIFU thermal ablations in the abdomen, providing the
      possibility to re-optimize the therapy plan on-the-fly with the patient on the
      interventional table. Moreover, we have demonstrated that even under clinical
      conditions, the proposed approach is fully capable of continuously ensuring the
      spatial fidelity between the different phases of the therapeutic work-flow.

PMID- 29043084
TI  - Multi-species genetic connectivity in a terrestrial habitat network.
AB  - BACKGROUND: Habitat fragmentation reduces genetic connectivity for multiple
      species, yet conservation efforts tend to rely heavily on single-species
      connectivity estimates to inform land-use planning. Such conservation activities
      may benefit from multi-species connectivity estimates, which provide a simple and
      practical means to mitigate the effects of habitat fragmentation for a larger
      number of species. To test the validity of a multi-species connectivity model, we
      used neutral microsatellite genetic datasets of Canada lynx (Lynx canadensis),
      American marten (Martes americana), fisher (Pekania pennanti), and southern
      flying squirrel (Glaucomys volans) to evaluate multi-species genetic connectivity
      across Ontario, Canada. RESULTS: We used linear models to compare node-based
      estimates of genetic connectivity for each species to point-based estimates of
      landscape connectivity (current density) derived from circuit theory. To our
      knowledge, we are the first to evaluate current density as a measure of genetic
      connectivity. Our results depended on landscape context: habitat amount was more
      important than current density in explaining multi-species genetic connectivity
      in the northern part of our study area, where habitat was abundant and
      fragmentation was low. In the south however, where fragmentation was prevalent,
      genetic connectivity was correlated with current density. Contrary to our
      expectations however, locations with a high probability of movement as reflected
      by high current density were negatively associated with gene flow. Subsequent
      analyses of circuit theory outputs showed that high current density was also
      associated with high effective resistance, underscoring that the presence of
      pinch points is not necessarily indicative of gene flow. CONCLUSIONS: Overall,
      our study appears to provide support for the hypothesis that landscape pattern is
      important when habitat amount is low. We also conclude that while current density
      is proportional to the probability of movement per unit area, this does not imply
      increased gene flow, since high current density tends to be a result of
      neighbouring pixels with high cost of movement (e.g., low habitat amount). In
      other words, pinch points with high current density appear to constrict gene
      flow.

PMID- 29043086
TI  - Hepatitis B vaccination coverage and the determinants of vaccination among health
      care workers in selected health facilities in Lusaka district, Zambia: an
      exploratory study.
AB  - BACKGROUND: Hepatitis B is a viral infection of the liver and causes both acute
      and chronic disease. It is transmitted through contact with an infected person's
      bodily fluids. It is an occupational hazard for healthcare workers and can be
      prevented by the administration of a vaccine. It is recommended that healthcare
      workers be vaccinated against vaccine preventable diseases including hepatitis B.
      The study objective was to determine the prevalence and determinants of hepatitis
      B vaccination among healthcare workers in selected health facilities in Lusaka.
      METHODS: The study took place in seven health facilities across Lusaka district
      in Zambia. A total sample size of 331 healthcare workers was selected of which;
      90 were nurses, 88 were doctors, 86 were laboratory personnel and 67 were general
      workers. A self-administered structured questionnaire was given to a total of 331
      healthcare workers. Investigator led stepwise approach was used to select the
      best predictor variables in a multiple logistic regression model and all analyses
      were performed using STATA software, version 12.1 SE (Stata Corporation, College
      Station, TX, USA). RESULTS: Only 64(19.3%) of the healthcare workers were
      vaccinated against hepatitis B, with 35 (54.7%) of these being fully vaccinated
      and 29 (45.3%) partially vaccinated. Analysis showed that; age of the healthcare
      worker, sharp injuries per year and training in infection control were the
      variables that were statistically significant in predicting a healthcare worker's
      vaccination status. CONCLUSION: It is reassuring to learn that healthcare workers
      have knowledge regarding hepatitis B and the vaccine and are willing to be
      vaccinated against it. Health institutions should bear the cost for vaccinating
      staff and efforts should be made for appropriate health education regarding
      hepatitis B infection and its prevention. Establishment of policies on compulsory
      hepatitis B vaccination for healthcare workers in Zambia is recommended.

PMID- 29043085
TI  - A pilot open series of lamotrigine in DBT-treated eating disorders characterized
      by significant affective dysregulation and poor impulse control.
AB  - BACKGROUND: There is little effective psychopharmacological treatment for
      individuals with eating disorders who struggle with pervasive, severe affective
      and behavioral dysregulation. METHODS: This pilot open series evaluated
      lamotrigine, a mood stabilizer, in the treatment of patients with eating
      disorders who did not respond adequately to antidepressant medications. Nine
      women with anorexia nervosa- or bulimia nervosa-spectrum eating disorders in
      partial hospital or intensive outpatient dialectical behavior therapy (DBT)-based
      eating disorder treatment took lamotrigine for 147 +/- 79 days (mean final dose =
      161.1 +/- 48.6 mg/day). Participants completed standardized self-report measures
      of emotion dysregulation and impulsivity after lamotrigine initiation and
      approximately biweekly thereafter. Mood and eating disorder symptomatology were
      measured at lamotrigine initiation and at time of final assessment. RESULTS:
      Lamotrigine and concurrent DBT were associated with large reductions in self
      reported affective and behavioral dysregulation (ps < 0.01). Eating disorder and
      mood symptoms decreased moderately. CONCLUSIONS: Although our findings are
      limited by the confounds inherent in an open series, lamotrigine showed initial
      promise in reducing emotional instability and behavioral impulsivity in severely
      dysregulated eating-disordered patients. These preliminary results support
      further investigation of lamotrigine for eating disorders in rigorous controlled
      trials.

PMID- 29043087
TI  - Sleepiness while driving and shiftwork patterns among Korean bus drivers.
AB  - BACKGROUND: Sleepiness while driving has been regarded as a major cause of death
      due to traffic accidents. We compared the degree of sleepiness across five
      different working time periods (first, morning, post-lunch, afternoon, and last)
      among Korean bus drivers with different shift types (Daily two shift/Alternating
      day shift). METHOD: We interviewed 332 bus drivers with two shift types (Daily
      two shift, 128; Alternating day shift, 204). The questionnaire included
      demographic information (age, alcohol consumption and history of disease), a
      sleep disorder diagnosed by a doctor, job duration, the number of workdays in the
      past month, average working hours per workday and week, sleepiness while driving
      (Karolinska Sleepiness Scale), and sleeping time for both workdays and off-days.
      We conducted log-binomial regression analyses and produced prevalence ratios
      (PRs) of severe sleepiness (KSS >= 7) while driving with 95% confidence intervals
      (95% CI) to identify the difference in sleepiness for five working times between
      both groups. RESULTS: For the first and morning periods, there were no
      statistically significant differences in the KSS scores between the two groups.
      However, from lunch to last driving, drivers with Alternating day shift had a
      much larger proportion of severe sleepiness than those on Daily two shift.
      Thirteen (10.2%), 2 (1.6%) and 7 (5.5%) Daily two shift workers reported severe
      sleepiness in the post-lunch, afternoon and last periods. In contrast, 81
      (39.7%), 63 (30.9%) and 64 (31.4%) of Alternating day shift drivers experienced
      severe sleepiness during the post-lunch, afternoon and last driving periods (p <
      0.0001). According to the log-binomial regression analyses, Alternating day shift
      was associated with severe sleepiness from lunch to last driving. After adjusting
      for job duration, alcohol consumption and sleeping time on workdays, the PRs were
      3.97 (95% CI: 2.29-6.90) post-lunch, 18.26 (95% CI: 4.51-73.89) in the afternoon
      and 5.71 (95% CI: 2.51-12.99) for the last driving period. CONCLUSION: We found
      that Alternating day shift bus drivers suffered from more sleepiness while
      driving from lunch to last driving than Daily two shift bus drivers. This
      difference may be because Alternating day shift drivers had more irregular work
      schedules and longer working hours per day and week.

PMID- 29043088
TI  - The relationship between spontaneous abortion and female workers in the
      semiconductor industry.
AB  - BACKGROUND: This study investigated the relationship between job type and the
      risk for spontaneous abortion to assess the reproductive toxicity of female
      workers in the semiconductor industry. METHODS: A questionnaire survey was
      administered to current female workers of two semiconductor manufacturing plants
      in Korea. We included female workers who became pregnant at least 6 months after
      the start of their employment with the company. The pregnancy outcomes of 2,242
      female workers who experienced 4,037 pregnancies were investigated. Personnel
      records were used to assign the subjects to one of three groups: fabrication
      process workers, packaging process workers, and clerical workers. To adjust for
      within-person correlations between pregnancies, a generalized estimating equation
      was used. The logistic regression analysis was limited to the first pregnancy
      after joining the company to satisfy the assumption of independence among
      pregnancies. Moreover, we stratified the analysis by time period (pregnancy in
      the years prior to 2008 vs. after 2009) to reflect differences in occupational
      exposure based on semiconductor production periods. RESULTS: The risk for
      spontaneous abortion in female semiconductor workers was not significantly higher
      for fabrication and packaging process workers than for clerical workers. However,
      when we stratified by time period, the odds ratio for spontaneous abortion was
      significantly higher for packaging process workers who became pregnant prior to
      2008 when compared with clerical workers (odds ratio: 2.21; 95% confidence
      interval: 1.01-4.81). CONCLUSIONS: When examining the pregnancies of female
      semiconductor workers that occurred prior to 2008, packaging process workers
      showed a significantly higher risk for spontaneous abortions than did clerical
      workers. The two semiconductor production periods in our study (prior to 2008 vs.
      after 2009) had different automated processes, chemical exposure levels, and
      working environments. Thus, the conditions prior to 2008 may have increased the
      risk for spontaneous abortions in packaging process workers in the semiconductor
      industry.

PMID- 29043089
TI  - Dermal and neural toxicity caused by acrylamide exposure in two Korean grouting
      workers: a case report.
AB  - BACKGROUND: Peripheral neuritis caused by acrylamide is well-known, and many
      Korean grouting workers are frequently exposed to acrylamide in grouting agents
      that are injected into cracked concrete. We recently encountered two cases of
      dermal and neural toxicity in Korean grouting workers with exposure to grouting
      agents that contained a high concentration of acrylamide. CASE PRESENTATION: The
      first case involved a 44-year-old man with 8 years of waterproofing experience.
      The patient developed peeling skin on both hands while grouting, which progressed
      to systemic neurological symptoms, such as reduced sensory function and strength.
      The patient was diagnosed with peripheral neuropathy caused by acrylamide
      exposure, and fully recovered after conservative treatment and withdrawal of
      exposure to the grouting agent. The second case involved a 34-year-old man with
      10 years of grouting experience. The patient initially experienced weakness in
      both legs, which progressed to weakness in his arms and uncontrolled phonation.
      After being hospitalized, he was diagnosed with cerebellar ataxia and peripheral
      neuropathy caused by acrylamide exposure, and was discharged after conservative
      treatment. Our follow-up investigation revealed that both workers were recently
      exposed to grouting agents that contained higher concentrations of acrylamide,
      compared to the agents that they had previously been using. CONCLUSIONS: Both
      workers had workplace acrylamide exposure through dermal contact plus inhalation
      of dust and vapor, which led to the neural toxicity and dermatitis. Therefore,
      government studies are needed to investigate the current status of workplace
      acrylamide use, and to protect workers from the hazardous effects of using
      acrylamide-containing grouting agents.

PMID- 29043090
TI  - The use of infrared thermography to detect the stages of estrus cycle and
      ovulation time in anatolian shepherd dogs.
AB  - BACKGROUND: The aim of the study is to evaluate the effectiveness of
      thermographic monitoring, using the temperature changes of perianal and
      perivulvar areas for the determination of estrus in Anatolian Shepherd bitches.
      Fifteen bitches were used in the study. Blood and vaginal smear samples were
      collected and thermographic monitoring of perianal and perivulvar areas were
      carried out starting from proestrus to early diestrus. Also, external signs of
      estrus were investigated. Smear samples were evaluated by light microscopy after
      Diff-Quik staining method and superficial and keratinized superficial cells were
      determined as percentage (S + KS%). Progesterone and luteinizing hormone
      measurements were done by radioimmunoassay. The difference in temperature between
      perianal and perivulvar areas was evaluated through thermographic images by FLIR
      ResearchIR Software. RESULTS: According to the results obtained from the study,
      differences between progesterone and S + KS% were statistically significant (P <
      0,05). Although temperature showed increase and decrease with progesterone and S
      + KS%, the differences were not important statistically (P > 0,05). Serum
      luteinizing hormone levels did not sign any difference (P > 0,05). CONCLUSIONS:
      As a result, thermographic monitoring alone is not enough for estrus detection in
      Anatolian Shepherd bitches. However, it can be used to assist the actual estrus
      detection technique in terms of providing some foreknowledge by evaluating the
      differences in temperature.

PMID- 29043091
TI  - HOPE: Help fOr People with money, employment, benefit or housing problems: study
      protocol for a randomised controlled trial.
AB  - BACKGROUND: Self-harm and suicide increase in times of economic recession.
      Factors including job loss, austerity measures, financial difficulties and house
      repossession contribute to the risk. Vulnerable individuals commonly experience
      difficulties in navigating the benefits system and in accessing the available
      sources of welfare and debt advice, and this contributes to their distress. Our
      aim is to determine the feasibility and acceptability of a brief psychosocial
      intervention (the "HOPE" service) for people presenting to hospital emergency
      departments (ED) following self-harm or in acute distress because of financial,
      employment, or welfare (benefit) difficulties. METHOD: A pilot study including
      randomisation will be employed to determine whether it is possible to undertake a
      full-scale trial. Twenty people presenting to the ED who have self-harmed, have
      suicidal thoughts and depression and/or are in crisis and where financial,
      employment or benefit problems are cited as contributory factors will be asked to
      consent to random allocation to the intervention or control arm on a 2:1 basis.
      People who require secondary mental health follow-up will be excluded. Those
      randomised to the intervention arm will receive up to six sessions with a mental
      health worker who will provide practical help with financial and other problems.
      The mental health worker will use the motivational interviewing method in their
      interactions with participants. Control participants will receive one session
      signposting them to existing relevant support organisations. Participants will be
      followed up after 3 months. Participants and the mental health workers will take
      part in qualitative interviews to enable refinement of the intervention. The
      acceptability of outcome measures including the PHQ-9, GAD-7, repeat self-harm,
      EQ5D-5L and questions about debt, employment and welfare benefits will be
      explored. DISCUSSION: This study will assess whether a full-scale randomised
      trial of this novel intervention to prevent self-harm among those distressed
      because of financial difficulties is feasible, including the acceptability of
      randomisation, potential rate of recruitment and the acceptability of outcome
      measures. TRIAL REGISTRATION: ISRCTN58531248.

PMID- 29043092
TI  - Twenty-seven-gauge vitrectomy for combined tractional and rhegmatogenous retinal
      detachment involving the macula associated with proliferative diabetic
      retinopathy.
AB  - BACKGROUND: To report our experience using 27-gauge pars plana vitrectomy (PPV)
      system for treating patients with combined tractional and rhegmatogenous retinal
      detachments (CTRRD) involving the macula associated with proliferative diabetic
      retinopathy (PDR). METHODS: Retrospective noncomparative interventional cases
      series of 12 patients with CTRRD associated with PDR who underwent 3-port,
      transconjunctival 27-gauge PPV by a single surgeon. Main outcome measures were
      change in Snellen best corrected visual acuity (BCVA) and occurrence of intra-
      and post-operative complications. RESULTS: Twelve eyes from 12 patients (9 men
      and 3 women) underwent 27-gauge PPV. Mean follow-up was 17 months (range 8-26
      months). Preoperatively, BCVA of 20/400 or better was recorded in only 2 of 12
      (16.7%) eyes. Postoperatively, BCVA improved to 20/400 or better in 11 of 12
      (91.7%) eyes at 6 months (P = 0.001). At last follow-up, BCVA of 20/400 or better
      was recorded in 10 of 12 (83.3%), in comparison to 2 (16.7%) eyes at baseline (P
      = 0.004). The only intraoperative complication was an iatrogenic break in 1 eye
      (8.3%). Postoperative complications included vitreous hemorrhage in 4 eyes
      (33.3%) and transient ocular hypertension in 3 eyes (25.0%). At final follow-up
      anatomic success was confirmed in all eyes. CONCLUSION: The current study
      findings suggest that 27-gauge PPV is a safe and promising surgical technology
      for treating patients with CTRRD involving the macula associated with PDR.
      Smaller gauge instruments and higher cutting rates may facilitate the dissection
      and shaving of fibrovascular membranes, while minimizing intra- and post
      operative complications.

PMID- 29043093
TI  - Anatomical study of petrous and cavernous parts of internal carotid artery.
AB  - The petrous and cavernous parts of internal carotid artery (ICA) are obscure and
      are not readily accessible to observation/imaging. These parts have broad
      biological and medical interest because of their peculiar shape. Given the their
      clinical importance and the scarce data available based mostly on imaging, the
      present study was aimed at studying these parts of ICA by dissection. The study
      was carried out on 56 ICAs obtained from embalmed adult cadavers and 10 ICAs from
      five fetuses. The foetal ICAs were studied in situ. The morphometric analysis of
      the adult ICA was done after its removal from cranial cavity to gain an insight
      into the geometry of the vessel, i.e., length, various bends, and diameters at
      various locations. ICAs in fetuses ran a relatively straighter course taking
      gentle curves at three positions (two intrapetrous, one cavernous). Adult ICAs
      were more tortuous and exhibited greater variability in length and angulations.
      The length of respective portions of the ICA correlate negatively with the
      measure of angles. The angles in the petrous and cavernous parts were positively
      correlated to each other. The carotid siphon was positively, highly significantly
      correlated to other angles. Longer vessels are more tortuous with acute bends. An
      acute carotid siphon is an indication of more tortuous ICA. The findings of the
      present study have created a reference data of unsuspected adult population and
      has potential implications for studying cause/effect relationship of vessel
      geometry and hemodynamic factors.

PMID- 29043094
TI  - Mid-foot retinaculum: an unrecognized entity.
AB  - Retinacula are thickenings of deep fascia in the region of joints that hold down
      the tendons preventing them from bowing out of position. In the region of ankle,
      number of such retinacula have been described. Retinacula like superior and
      inferior extensor retinacula have been described which hold down the tendons of
      leg muscles passing to the foot beneath them. As the extensor tendons of the leg
      have more distal attachment to the toes, the present study was conducted to
      ascertain the presence of any additional retinaculum in the mid-foot region,
      which would tie down the tendons for their effective action at the distal joints.
      The aim was also to determine the attachments of the retinaculum, if present as
      well as the structures passing beneath them. Fifty cadaveric feet were dissected
      carefully for this purpose. Presence of an additional extensor retinaculum distal
      to the inferior band of inferior extensor retinaculum in the mid-foot region was
      found in 22 feet. Besides the extensor tendons, medial terminal branch of deep
      peroneal nerve and dorsalis pedis artery was found to pass beneath the
      retinaculum. A partial or complete mid-foot retinaculum existed in the mid-foot
      region covering the tarsometatarsal joints in about half of study population.
      Functionally, this retinaculum may prevent bowstringing of the extensor tendons,
      clinically it may predispose to entrapment of deep peroneal nerve mimicking
      anterior tarsal tunnel syndrome.

PMID- 29043095
TI  - Applied anatomy, today's requirement for clinical medicine courses.
AB  - Anatomy as an indispensable part of the medical curricula, offering impeccable
      knowledge, prepares the students to enter the practical atmosphere. The aim of
      this study was to evaluate the clinical application of anatomy courses of the
      medical students in Zanjan University of Medical Sciences. This cross-sectional
      study was conducted in 2015 with census sampling on all clinical students
      (trainees and interns). To collect feedback from students, the questionnaire
      designed by researchers was used. The Likert rating scale of very high, high,
      medium, low, and very low was considered and scores of 5 (very high) to 1 (very
      low) were applied. Data were analyzed by SPSS software. Among the courses of
      anatomy, trunk anatomy has the greatest impact on clinical courses of medical
      students (P<0.001). Subjects of muscular system, lymphatic system, vascular
      system, and nervous system were of significant clinical application during
      clinical periods; however, no significant clinical application observed for
      skeletal system (P<0.05). Teaching clinical tips by professors can help improve
      the performance of medical students in clinical education. In addition, using
      three-dimensional anatomical software is suggested as well.

PMID- 29043096
TI  - Sex determination using humeral dimensions in a sample from KwaZulu-Natal: an
      osteometric study.
AB  - The morphological characteristics of the humeral bone has been investigated in
      recent times with studies showing varying degrees of sexual dimorphism.
      Osteologists and forensic scientists have shown that sex determination methods
      based on skeletal measurements are population specific, and these population
      specific variations are present in many body dimensions. The present study aims
      to establish sex identification using osteometric standards for the humerus in a
      contemporary KwaZulu-Natal population. A total of 11 parameters were measured in
      a sample of n=211 humeri (males, 113; females, 98) from the osteological
      collection in the Discipline of Clinical Anatomy, Nelson R. Mandela School of
      Medicine, University of KwaZulu-Natal, Durban, South Africa. The difference in
      means for nearly all variables were found to be significantly higher in males
      compared to females (P<0.01) with the most effective single parameter for
      predicting sex being the vertical head diameter having an accuracy of 82.5%.
      Stepwise discriminant analysis increased the overall accuracy rate to 87.7% when
      all measurements were jointly applied. We conclude that the humerus is an
      important bone which can be reliably used for sex determination based on standard
      metric methods despite minor tribal or ancestral differences amongst an otherwise
      homogenous population.

PMID- 29043097
TI  - Histological study on the effect of nicotine on adult male guinea pig thin skin.
AB  - Tobacco smoking has been identified as an important factor in premature skin
      aging to detect the histological changes occurred in adult male guinea pig thin
      skin under the influence of low and high doses of nicotine; which constitutes
      approximately 0.6%-3.0% of the dry weight of tobacco. Fifteen adult male
      pigmented guinea pigs were equally divided into three groups: group I, control;
      group IIA, low dose nicotine treated; 3 mg/kg subcutaneously for 4 weeks; and
      group IIB, high dose nicotine treated; 6 mg/kg subcutaneously for 4 weeks.
      Specimens from the back thin skin were processed for light and electron
      microscopy. Nicotine administration revealed flattened dermo-epidermal junction
      and reduced rete ridges formation. Collagen bundles were disorganized with
      increased spaces between them. A reduction in the amount of elastic fibers in the
      dermis were also observed compared to group I. Ultrastructurally, keratinocytes
      had hyperchromatic nuclei, intracytoplasmic vacuoles, disruption of desmosomal
      junctions, irregular tonofilaments distribution, and increased inter-cellular
      spaces. These changes were more pronounced with high dose nicotine
      administration. The epidermal thickness was reduced in low dose nicotine
      administration. But, high dose nicotine administration revealed increased
      epidermal thickness compared to the control group. Nicotine induced structural
      changes of adult male guinea pig thin skin. These changes were more pronounced
      with high dose nicotine administration.

PMID- 29043098
TI  - Spermidine is protective against kidney ischemia and reperfusion injury through
      inhibiting DNA nitration and PARP1 activation.
AB  - Kidney ischemia and reperfusion injury (IRI) is associated with a high mortality
      rate, which is attributed to tubular oxidative and nitrative stresses; however,
      an effective approach to limit IRI remains elusive. Spermidine, a naturally
      occurring polyamine, protects yeast cells against aging through the inhibition of
      oxidative stress and necrosis. In the present study, spermidine supplementation
      markedly attenuated histological damage and kidney dysfunction during IRI. In
      addition, exogenous spermidine potently inhibited poly(ADP-ribose) polymerase 1
      (PARP1) activation and DNA nitrative/oxidative stress following IRI. Conversely,
      inhibition of ornithine decarboxylase (ODC) via siRNA transfection in vivo
      significantly enhanced DNA nitration, PARP1 activation, and functional damage
      during IRI. Finally, in ODC knockdown kidneys, PARP1 inhibition attenuated
      histological and functional damage induced by IRI, but not DNA nitrative stress.
      In conclusion, these data suggest that spermidine protects kidneys against IRI
      through blocking DNA nitration and PARP1 activation and this finding provides a
      novel target for prevention of acute kidney injury including IRI.

PMID- 29043099
TI  - Lithium ameliorates rat spinal cord injury by suppressing glycogen synthase
      kinase-3beta and activating heme oxygenase-1.
AB  - Glycogen synthase kinase (GSK)-3beta and related enzymes are associated with
      various forms of neuroinflammation, including spinal cord injury (SCI). Our aim
      was to evaluate whether lithium, a non-selective inhibitor of GSK-3beta,
      ameliorated SCI progression, and also to analyze whether lithium affected the
      expression levels of two representative GSK-3beta-associated molecules, nuclear
      factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) (a target
      gene of Nrf-2). Intraperitoneal lithium chloride (80 mg/kg/day for 3 days)
      significantly improved locomotor function at 8 days post-injury (DPI); this was
      maintained until 14 DPI (P<0.05). Western blotting showed significantly increased
      phosphorylation of GSK-3beta (Ser9), Nrf-2, and the Nrf-2 target HO-1 in the
      spinal cords of lithium-treated animals. Fewer neuropathological changes (e.g.,
      hemorrhage, inflammatory cell infiltration, and tissue loss) were observed in the
      spinal cords of the lithium-treated group compared with the vehicle-treated
      group. Microglial activation (evaluated by measuring the immunoreactivity of
      ionized calcium-binding protein-1) was also significantly reduced in the lithium
      treated group. These findings suggest that GSK-3beta becomes activated after SCI,
      and that a non-specific enzyme inhibitor, lithium, ameliorates rat SCI by
      increasing phosphorylation of GSK-3beta and the associated molecules Nrf-2 and HO
      1.

PMID- 29043100
TI  - Expression of glucose transporters in the developing rat skin.
AB  - We found the changed distribution of glucose transporter (GLUT) proteins in the
      skin during rat development. At 15 days of gestation, GLUT1 and 2 proteins were
      expressed in the stratum corneum of epidermal cells. In postnatal skin, however,
      GLUT1 and 2 exhibit different expression patterns. While GLUT1 expression becomes
      more restricted to the stratum basale with development, GLUT2 was found mainly in
      stratum spinosum and granulosum, but not being localized in the stratum basale at
      any stages of perinatal skin development. Considering all these, it can be
      speculated that each GLUT protein plays its specific role in different epidermal
      layers and that the glucose used in mammalian skin in utero could be originated
      from the amniotic fluid during skin development.

PMID- 29043101
TI  - Protective effect of Rhus verniciflua Stokes extract in an experimental model of
      post-menopausal osteoporosis.
AB  - Post-menopausal osteoporosis (PMO) is a major global human health concern. Owing
      to the need for therapeutic drugs without side effects, natural extracts
      containing various polyphenolic compounds that may exert estrogenic effects have
      been studied in depth. Rhus verniciflua Stokes (RVS), which has been used as a
      traditional herbal medicine for centuries in Korea, was recently revealed to
      exert estrogenic effects attributable to its bioactive ingredients sulfuretin and
      butein, which have strong estrogen receptor-binding affinities. In this study,
      the protective potential of RVS in PMO was evaluated by using an experimental
      animal model of PMO, which was established by ovariectomy (OVX) of female Sprague
      Dawley rats. The oral administration of RVS at 20 mg/kg or 100 mg/kg for 8 weeks
      markedly protected against OVX-induced atrophy of the uterine tube and reversed
      the elevation in the ratio of serum receptor activator of nuclear factor-kappaB
      ligand to osteoprotegerin, which is a marker of disease severity. In addition,
      RVS inhibited OVX-induced tibia bone loss, activated osteogenic activity, and
      suppressed osteoclastic activity in the tibial epiphyseal plate, a region of bone
      remodeling. Collectively, these factors indicated that the oral intake of RVS
      might be beneficial for the prevention of PMO.

PMID- 29043102
TI  - The distribution of calbindin-D28k, parvalbumin, and calretinin immunoreactivity
      in the inferior colliculus of circling mouse.
AB  - The circling mice with tmie gene mutation are known as an animal deafness model,
      which showed hyperactive circling movement. Recently, the reinvestigation of
      circling mouse was performed to check the inner ear pathology as a main lesion of
      early hearing loss. In this trial, the inner ear organs were not so damaged to
      cause the hearing deficit of circling (cir/cir) mouse at 18 postnatal day (P18)
      though auditory brainstem response data indicated hearing loss of cir/cir mice at
      P18. Thus, another mechanism may be correlated with the early hearing loss of
      cir/cir mice at P18. Hearing loss in the early life can disrupt the ascending and
      descending information to inferior colliculus (IC) as integration site. There
      were many reports that hearing loss could result in the changes in Ca2+
      concentration by either cochlear ablation or genetic defect. However, little was
      known to be reported about the correlation between the pathology of IC and Ca2+
      changes in circling mice. Therefore, the present study investigated the
      distribution of calcium-binding proteins (CaBPs), calbindin-D28k, parvalbumin,
      and calretinin immunoreactivity (IR) in the IC to compare among wild-type (+/+),
      heterozygous (+/cir), and homozygous (cir/cir) mice by immunohistochemistry. The
      decreases of CaBPs IR in cir/cir were statistically significant in the neurons as
      well as neuropil of IC. Thus, this study proposed overall distributional
      alteration of CaBPs IR in the IC caused by early hearing defect and might be
      helpful to elucidate the pathology of central auditory disorder related with Ca2+
      metabolism.

PMID- 29043103
TI  - Unusual muscle of the anterior neck: cadaveric findings with surgical
      applications.
AB  - The omohyoid muscle typically has an inferior belly originating from the superior
      border of the scapula, and then passes deep to the sternocleidomastoid muscle
      where its superior belly passes almost vertically upward next to the lateral
      border of sternohyoid to attach to the inferior border of the body of the hyoid
      bone lateral to the insertion of sternohyoid. Herein, we report an unusual
      variant of the omohyoid and sternohyoid muscles. As the omohyoid muscle is
      commonly used as a surgical landmark during neck dissections, knowledge of its
      variations such as the one described in the current report is important to
      surgeons.

PMID- 29043104
TI  - Undescended cecum with accessory right colic artery: a rare case report.
AB  - Midgut malrotation and incomplete rotation are common causes of neonatal
      intestinal obstruction. At end of 10 week of intrauterine life, cecum will be
      placed in subhepatic region temporarily and descends to right lower quadrant by
      eleventh week. Arrest of cecum in subhepatic region or undescended cecum is a
      rare congenital anomaly of mid gut. Usually, it remains asymptomatic and is
      diagnosed incidentally. If any pathology occurs in anomalous part, like
      appendicitis then the diagnosis and treatment will be challenging in all age
      groups. Variation in blood supply have also been reported with anomalies leading
      to iatrogenic injuries during colonoscopy and surgeries. Lack of knowledge of
      these rare variations may lead to delayed diagnosis of appendicitis leading to
      perforation and surgical emergencies. In the present case, we describe an
      undescended cecum and its associated variation in branching pattern of superior
      mesenteric artery.

PMID- 29043105
TI  - Retraction notice to "Therapeutic effect of prostaglandin E1 in monocrotaline
      induced pulmonary arterial hypertension rats" by Lee JC (Anat Cell Biol
      2017;50:60-8).
AB  - [This retracts the article on p. 60 in vol. 50, PMID: 28417056.].

PMID- 29043106
TI  - Sediment microbial taxonomic and functional diversity in a natural salinity
      gradient challenge Remane's "species minimum" concept.
AB  - Several models have been developed for the description of diversity in estuaries
      and other brackish habitats, with the most recognized being Remane's Artenminimum
      ("species minimum") concept. It was developed for the Baltic Sea, one of the
      world's largest semi-enclosed brackish water body with a unique permanent
      salinity gradient, and it argues that taxonomic diversity of macrobenthic
      organisms is lowest within the horohalinicum (5 to 8 psu). The aim of the present
      study was to investigate the relationship between salinity and sediment microbial
      diversity at a freshwater-marine transect in Amvrakikos Gulf (Ionian Sea, Western
      Greece) and assess whether species composition and community function follow a
      generalized concept such as Remane's. DNA was extracted from sediment samples
      from six stations along the aforementioned transect and sequenced for the 16S
      rRNA gene using high-throughput sequencing. The metabolic functions of the OTUs
      were predicted and the most abundant metabolic pathways were extracted. Key
      abiotic variables, i.e., salinity, temperature, chlorophyll-a and oxygen
      concentration etc., were measured and their relation with diversity and
      functional patterns was explored. Microbial communities were found to differ in
      the three habitats examined (river, lagoon and sea) with certain taxonomic groups
      being more abundant in the freshwater and less in the marine environment, and
      vice versa. Salinity was the environmental factor with the highest correlation to
      the microbial community pattern, while oxygen concentration was highly correlated
      to the metabolic functional pattern. The total number of OTUs showed a negative
      relationship with increasing salinity, thus the sediment microbial OTUs in this
      study area do not follow Remane's concept.

PMID- 29043107
TI  - The intervals method: a new approach to analyse finite element outputs using
      multivariate statistics.
AB  - BACKGROUND: In this paper, we propose a new method, named the intervals' method,
      to analyse data from finite element models in a comparative multivariate
      framework. As a case study, several armadillo mandibles are analysed, showing
      that the proposed method is useful to distinguish and characterise biomechanical
      differences related to diet/ecomorphology. METHODS: The intervals' method
      consists of generating a set of variables, each one defined by an interval of
      stress values. Each variable is expressed as a percentage of the area of the
      mandible occupied by those stress values. Afterwards these newly generated
      variables can be analysed using multivariate methods. RESULTS: Applying this
      novel method to the biological case study of whether armadillo mandibles differ
      according to dietary groups, we show that the intervals' method is a powerful
      tool to characterize biomechanical performance and how this relates to different
      diets. This allows us to positively discriminate between specialist and
      generalist species. DISCUSSION: We show that the proposed approach is a useful
      methodology not affected by the characteristics of the finite element mesh.
      Additionally, the positive discriminating results obtained when analysing a
      difficult case study suggest that the proposed method could be a very useful tool
      for comparative studies in finite element analysis using multivariate statistical
      approaches.

PMID- 29043108
TI  - Mysterious inhibitory cell regulator investigated and found likely to be
      secretogranin II related.
AB  - In the context of a hunt for a postulated hormone that is tissue-mass inhibiting
      and reproductively associated, there is described probable relatedness to a
      granin protein. A 7-8 kDa polypeptide candidate (gels/MS) appeared in a bioassay
      guided fractionation campaign involving sheep plasma. An N-terminal sequence of
      14 amino acids was obtained for the polypeptide by Edman degradation.
      Bioinformatics and molecular biology failed to illuminate any ovine or non-ovine
      protein which might relate to this sequence. The N-terminal sequence was
      synthesized as the 14mer EPL001 peptide and surprisingly found to be inhibitory
      in an assay in vivo of compensatory renal growth in the rat and modulatory of
      nematode fecundity, in line with the inhibitory hormone hypothesis. Antibodies
      were raised to EPL001 and their deployment upheld the hypothesis that the EPL001
      amino acid sequence is meaningful and relevant, notwithstanding bioinformatic
      obscurity. Immunohistochemistry (IHC) in sheep, rodents and humans yielded
      staining of seeming endocrine relevance (e.g. hypothalamus, gonads and
      neuroendocrine cells in diverse tissues), with apparent upregulation in certain
      human tumours (e.g. pheochromocytoma). Discrete IHC staining in Drosophila
      melanogaster embryo brain was seen in glia and in neuroendocrine cells, with
      staining likely in the corpus cardiacum. The search for the endogenous antigen
      involved immunoprecipitation (IP) followed by liquid chromatography and mass
      spectrometry (LC-MS). Feedstocks were PC12 conditioned medium and aqueous extract
      of rat hypothalamus-both of which had anti-proliferative and pro-apoptotic
      effects in an assay in vitro involving rat bone marrow cells, which inhibition
      was subject to prior immunodepletion with an anti-EPL001 antibody-together with
      fruit fly embryo material. It is concluded that the mammalian antigen is likely
      secretogranin II (SgII) related. The originally seen 7-8 kDa polypeptide is
      suggested to be a new proteoform of secretogranin II of ~70 residues, SgII-70,
      with the anti-EPL001 antibody seeing a discontinuous epitope. The fly antigen is
      probably Q9W2X8 (UniProt), an uncharacterised protein newly disclosed as a granin
      and provisionally dubbed macrogranin I (MgI). SgII and Q9W2X8 merit further
      investigation in the context of tissue-mass inhibition.

PMID- 29043109
TI  - Multigene phylogeny of the scyphozoan jellyfish family Pelagiidae reveals that
      the common U.S. Atlantic sea nettle comprises two distinct species (Chrysaora
      quinquecirrha and C. chesapeakei).
AB  - BACKGROUND: Species of the scyphozoan family Pelagiidae (e.g., Pelagia noctiluca,
      Chrysaora quinquecirrha) are well-known for impacting fisheries, aquaculture, and
      tourism, especially for the painful sting they can inflict on swimmers. However,
      historical taxonomic uncertainty at the genus (e.g., new genus Mawia) and species
      levels hinders progress in studying their biology and evolutionary adaptations
      that make them nuisance species, as well as ability to understand and/or mitigate
      their ecological and economic impacts. METHODS: We collected nuclear (28S rDNA)
      and mitochondrial (cytochrome c oxidase I and 16S rDNA) sequence data from
      individuals of all four pelagiid genera, including 11 of 13 currently recognized
      species of Chrysaora. To examine species boundaries in the U.S. Atlantic sea
      nettle Chrysaora quinquecirrha, specimens were included from its entire range
      along the U.S. Atlantic and Gulf of Mexico coasts, with representatives also
      examined morphologically (macromorphology and cnidome). RESULTS: Phylogenetic
      analyses show that the genus Chrysaora is paraphyletic with respect to other
      pelagiid genera. In combined analyses, Mawia, sampled from the coast of Senegal,
      is most closely related to Sanderia malayensis, and Pelagia forms a close
      relationship to a clade of Pacific Chrysaora species (Chrysaora achlyos,
      Chrysaora colorata, Chrysaora fuscescens, and Chrysaora melanaster). Chrysaora
      quinquecirrha is polyphyletic, with one clade from the U.S. coastal Atlantic and
      another in U.S. Atlantic estuaries and Gulf of Mexico. These genetic differences
      are reflected in morphology, e.g., tentacle and lappet number, oral arm length,
      and nematocyst dimensions. Caribbean sea nettles (Jamaica and Panama) are
      genetically similar to the U.S. Atlantic estuaries and Gulf of Mexico clade of
      Chrysaora quinquecirrha. DISCUSSION: Our phylogenetic hypothesis for Pelagiidae
      contradicts current generic definitions, revealing major disagreements between
      DNA-based and morphology-based phylogenies. A paraphyletic Chrysaora raises
      systematic questions at the genus level for Pelagiidae; accepting the validity of
      the recently erected genus Mawia, as well as past genera, will require the
      creation of additional pelagiid genera. Historical review of the species
      delineating genetic and morphological differences indicates that Chrysaora
      quinquecirrha Desor 1848 applies to the U.S. Coastal Atlantic Chrysaora species
      (U.S. Atlantic sea nettle), while the name C. chesapeakei Papenfuss 1936 applies
      to the U.S. Atlantic estuarine and Gulf of Mexico Chrysaora species (Atlantic bay
      nettle). We provide a detailed redescription, with designation of a neotype for
      Chrysaora chesapeakei, and clarify the description of Chrysaora quinquecirrha.
      Since Caribbean Chrysaora are genetically similar to Chrysaora chesapeakei, we
      provisionally term them Chrysaora c.f. chesapeakei. The presence of Mawia
      benovici off the coast of Western Africa provides a potential source region for
      jellyfish introduced into the Adriatic Sea in 2013.

PMID- 29043110
TI  - Neurodynamic mobilization and foam rolling improved delayed-onset muscle soreness
      in a healthy adult population: a randomized controlled clinical trial.
AB  - OBJECTIVES: Compare the immediate effects of a Neurodynamic Mobilization (NM)
      treatment or foam roller (FR) treatment after DOMS. DESIGN: Double blind
      randomised clinical trial. SETTING: The participants performed 100 drop jumps (5
      sets of 20 repetitions, separated by 2 min rests) from a 0.5-m high box in a
      University biomechanics laboratory to induce muscle soreness. The participants
      were randomly assigned in a counter-balanced fashion to either a FR or NM
      treatment group. PARTICIPANTS: Thirty-two healthy subjects (21 males and 11
      females, mean age 22.6 +/- 2.2 years) were randomly assigned into the NM group (n
      = 16) or the FR group (n = 16). MAIN OUTCOME MEASURES: The numeric pain rating
      scale (NPRS; 0-10), isometric leg strength with dynamometry, surface
      electromyography at maximum voluntary isometric contraction (MVIC) and muscle
      peak activation (MPA) upon landing after a test jump were measured at baseline,
      48 h after baseline before treatment, and immediately after treatment. RESULTS:
      Both groups showed significant reduction in NPRS scores after treatment (NM: 59%,
      p < .01; FR: 45%, p < .01), but no difference was found between them (p > .05).
      The percentage change improvement in the MVIC for the rectus femoris was the only
      significant difference between the groups (p < 0.05) at post-treatment. After
      treatment, only the FR group had a statistically significant improvement (p <
      0.01) in strength compared to pre-treatment. CONCLUSION: Our results illustrate
      that both treatments are effective in reducing pain perception after DOMS whereas
      only FR application showed differences for the MVIC in the rectus femoris and
      strength.

PMID- 29043111
TI  - A retrospective study: does upper airway morphology differ between non-positional
      and positional obstructive sleep apnea?
AB  - OBJECTIVE: The objective of this study was to explore the differences in upper
      airway morphology between positional (POSA) and non-positional (NPOSA)
      obstructive sleep apnea. METHODS: This retrospective study enrolled 75 patients
      (45 NPOSA and 30 POSA) who underwent polysomnography (PSG) and computed
      tomography (CT). The differences in, and relationships of, the PSG values and CT
      data between POSA and NPOSA were analyzed. RESULTS: Significant (p < 0.05)
      differences between the two groups were found in the apnea/hypopnea index (AHI),
      lateral-AHI (L-AHI), soft palate length (SPL), cross-sectional palatopharyngeal
      area, and the coronal diameter (CD) of the palatopharyngeal area at the narrowest
      part of the glossopharynx, which were all higher in POSA, except for SPL, AHI,
      and L-AHI. L-AHI was correlated with the cross-sectional area (r =  - 0.306, p =
      0.008) and CD (r =  - 0.398, p < 0.001) of the palatopharyngeal area, the cross
      sectional area (r =  - 0.241, p = 0.038) and CD (r =  - 0.297, p = 0.010) of the
      narrowest level of the glossopharynx, the CD of the glossopharynx (r = 0.284, p =
      0.013), body mass index (BMI, r = 0.273, p = 0.018), SPL (r = 0.284, p = 0.014),
      and vallecula-tip of tongue (r = 0.250, p = 0.030). The SPL and CD at the
      narrowest part of the glossopharynx were included in the simplified screening
      model. CONCLUSIONS: In NPOSA, the CD of the upper airway was smaller, and the
      soft palate was longer, than in POSA. These differences may play significant
      roles in explaining the main differences between NPOSA and POSA.

PMID- 29043112
TI  - Tumor-infiltrating CD8+ lymphocytes predict different clinical outcomes in organ-
      and non-organ-confined urothelial carcinoma of the bladder following radical
      cystectomy.
AB  - Tumor-infiltrating lymphocytes (TILs) are associated with better clinical
      outcomes in many tumors. TILs represent a cell-mediated immune response against
      the carcinoma. CD8+ TILs are a crucial component of cell-mediated immunity. The
      significance of CD8+ TILs has not been reported respectively in organ- and non
      organ-confined urothelial carcinoma (UC) of the bladder. We explored the
      prognostic value of CD8+ TILs in the two groups. The presence of CD8+ TILs was
      assessed by immunohistochemical staining of whole tissue sections from 75 organ
      and 51 non-organ-confined disease patients with long-term follow-up, and its
      correlation with clinicopathological features and overall survival (OS) was
      determined. The CD8+ TIL immunohistochemical staining score was 0 (<1%), 1
      (>=1%), 2 (>=5%), or 3 (>=10%) based on the percentage of positively stained
      cells out of total cells. A patient was considered CD8 negative if the score was
      0. There were no associations between CD8+ TILs and age, sex, nuclear grade, and
      adjuvant or neoadjuvant chemotherapy in organ- and non-organ-confined disease.
      The presence of CD8+ TILs was seen more frequently in pTa-1 than pT2 stage (p =
      0.033) in organ-confined disease. No associations between CD8+ TILs and pT stage,
      pN stage were found in non-organ-confined disease. CD8+ TILs were associated with
      better OS (log-rank test, P = 0.036) in non-organ-confined disease, but with
      poorer OS (log-rank test, P = 0.040) in organ-confined disease by the Kaplan
      Meier method. In multivariate analysis, CD8+ TILs were an independent favorable
      prognostic factor in non-organ-confined disease, but were an independent
      unfavorable prognostic factor in organ-confined disease. These results suggest
      that CD8+ TILs have clinically significant anti-tumor activity in non-organ
      confined disease, but may have pro-tumor activity in organ-confined disease.
      Therefore, we should be cautious if CD8+ TILs are aimed to be exploited in the
      treatment of bladder cancer.

PMID- 29043113
TI  - Simultaneous Tracking of Cardiorespiratory Signals for Multiple Persons Using a
      Machine Vision System With Noise Artifact Removal.
AB  - Most existing non-contact monitoring systems are limited to detecting
      physiological signs from a single subject at a time. Still, another challenge
      facing these systems is that they are prone to noise artifacts resulting from
      motion of subjects, facial expressions, talking, skin tone, and illumination
      variations. This paper proposes an efficient non-contact system based on a
      digital camera to track the cardiorespiratory signal from a number of subjects
      (up to six persons) at the same time with a new method for noise artifact
      removal. The proposed system relied on the physiological and physical effects as
      a result of the activity of the cardiovascular and respiratory systems, such as
      skin color changes and head motion. Since these effects are imperceptible to the
      human eye and highly affected by the noise variations, we used advanced signal
      and video processing techniques, including developing video magnification
      technique, complete ensemble empirical mode decomposition with adaptive noise,
      and canonical correlation analysis to extract the heart rate and respiratory rate
      from multiple subjects under the noise artifact assumptions. The experimental
      results of the proposed system had a significant correlation (Pearson's
      correlation coefficient = 0.9994, Spearman correlation coefficient = 0.9987, and
      root mean square error = 0.32) when compared with the conventional contact
      methods (pulse oximeter and piezorespiratory belt), which makes the proposed
      system a promising candidate for novel applications.

PMID- 29043114
TI  - Expression of STK11 gene and its promoter activity in MCF control and cancer
      cells.
AB  - Serine/threonine kinase gene (STK11) is identified as tumor suppressor gene whose
      mutation can lead to Peutz-Jeghers syndrome (PJS). STK11 is emerging as a
      multifunctional protein, it activates 14 different AMP-activated protein kinase
      (AMPK) family members, important in the regulation of cell polarity, cell cycle
      arrest, energy and hemostasis. Present study was designed to evaluate STK11 mRNA
      expression in MCF-7 cancer and MCF-10 normal breast cells lines. mRNA expression
      was studied by real-time PCR. Further, human STK11 promoter construct was fused
      to a luciferase reporter and transfected into both MCF-7 and MCF-10 cells to
      identify the promoter activity in these cells. STK11 mRNA was found significantly
      higher in MCF-7 compared to MCF-10 cells (p value < 0.0005) indicating its role
      in the onset of breast cancer. Interestingly, it was found that the promoter
      activity of STK11 gene in MCF-7 cells was also significantly higher when compared
      to MCF-10 cells (p value < 0.005). Positive correlation was observed in promoter
      activity and gene expression (p = 0.048, r2 = 0.587). This study for the first
      time relates the altered STK11 gene expression in breast cancer cells with
      altered promoter activity. The present finding may shed light on the new
      therapeutic approaches against breast cancer by targeting gene or its promoter.

PMID- 29043115
TI  - Regulation of different polyketide biosynthesis by green light in an endophytic
      fungus of mangrove leaf.
AB  - Light is an important environmental signal for many organisms. The light response
      reports of fungi usually focus on blue light and red light. Although the green
      light sensor has also been found in several fungi, the knowledge of the green
      light response in fungi is very limited. Halorosellinia sp. (No. 1403) is a light
      sensitive endophytic fungus of mangrove leaf. In this study, we explored the
      specific effects of monochromatic blue light, red light, and green light on
      polyketides biosynthesis in Halorosellinia sp. (No. 1403), respectively. The
      major polyketides produced in Halorosellinia sp. (No. 1403) are octaketides
      (1403C and 1403R) and heptaketide (griseofulvin). All monochromatic light
      enhanced octaketide biosynthesis and inhibited heptaketide biosynthesis to some
      extent compared with the dark condition. Most prominently, the total production
      of octaketides was increased by 76%, and the production of heptaketide was
      decreased by 73% under green light in bioreactor. Therefore, green light can not
      only influence the secondary metabolism in fungi, but also it can influence
      different biosynthetic pathways in different ways. We speculate that the
      significant effect of green light on mangrove leaf endophytic fungus
      Halorosellinia sp. (No. 1403) may be a kind of environmental adaptation to plant
      photosynthesis.

PMID- 29043116
TI  - A rapid and efficient DNA extraction method suitable for marine macroalgae.
AB  - Macroalgae are a diverse group of organisms. Marine macroalgae, in particular,
      have numerous medicinal and industrial applications. Molecular studies of
      macroalgae require suitable concentrations of DNA free of contaminants. At
      present, numerous protocols exist for DNA extraction from macroalgae. However,
      they are either time consuming, expensive or work only with few species. The
      method described in this study is rapid and efficient and applicable to different
      types of marine macroalgae. This method yields an average of 3.85 ug of DNA per
      50 mg of algal tissue, with an average purity of 1.88. The isolated DNA was
      suitable for PCR amplification of universal plastid region of macroalgae.

PMID- 29043117
TI  - An intra-abdominal abscess or "rind" as a consequence of peritoneal dialysis
      associated pseudomonas peritonitis.
AB  - BACKGROUND: Abdominal CT imaging has defined characteristics of two pathological
      entities specific to peritoneal dialysis patients. Both are associated with
      serious peritoneal complications. One is comprised of ascites accompanied by
      septation and loculated fluid pockets as a complication of bacterial peritonitis.
      The other is the syndrome of encapsulating peritoneal sclerosis. We present the
      evolution of a single, thick-walled fluid collection as a consequence of
      relapsing Pseudomonas aeruginosa peritonitis. The entity had distinctive features
      differing from either of the two previously described entities, and to our
      knowledge, has not been described previously. Our patient's radiological
      evolution resembled the formation of a pleural or peritoneal "rind." CONCLUSION:
      Peritonitis, as a result of Pseudomonas aeruginosa, may lead to "rind" formation
      as described with empyemas and is distinct from previously described intra
      abdominal pathologies in peritoneal dialysis patients.

PMID- 29043118
TI  - Acute pyelonephritis including an overlooked renal cell carcinoma.
AB  - Hidden renal mass is not evident during severe inflammation such as acute
      pyelonephritis, pyonephrosis, or renal abscess. Deceptive inflammatory
      presentations that can occur in aggressive synchronous renal malignancies can
      significantly delay the diagnosis of cancer. Herein, we report a case of acute
      pyelonephritis involving overlooked renal cell carcinoma.

PMID- 29043119
TI  - Thromboembolism in renal transplant artery due to atrial fibrillation.
AB  - BACKGROUND: Central and peripheral arterial thromboembolisms are well known
      complications of atrial fibrillation. We report the first case of thromboembolism
      in a renal transplant due to atrial fibrillation after changing anticoagulation
      treatment. CASE PRESENTATION: A 79-year-old woman who had undergone kidney
      transplantation in 2001 presented herself with abdominal pain and oliguria. Serum
      creatinine had been stable (130 - 150 umol/l) since transplantation, and, because
      of atrial fibrillation, the patient received oral anticoagulation treatment for
      many years until it was switched to aspirin 100 mg due to a cholecystectomy in
      2012. Three weeks thereafter is when the patient was admitted to our unit. In a
      computed tomography scan of the abdomen, multiple renal infarcts were detected.
      The thromboembolism resulted in a complete loss of transplant function. As the
      patient remained anuric, the transplant was declared to be lost,
      immunosuppression was reduced, and renal replacement therapy was commenced over a
      central catheter. However, the patient died the next day. CONCLUSION: Our case
      highlights the fact that changing anticoagulation treatment should be performed
      carefully and can be detrimental. The location of thromboembolism in renal
      transplant artery makes this case unique and has not ever been described thus
      far. As renal transplantation and risk factors for thromboembolism i.e., atrial
      fibrillation are increasing, embolization in renal transplant artery is a
      potential reason for abdominal pain and anuria; physicians should take this into
      consideration when treating transplanted patients.

PMID- 29043120
TI  - Is there a pathogenic association between Fabry's disease and IgA nephropathy?
AB  - Several cases of concurrent Fabry's disease and IgA nephropathy have been
      reported, but the pathogenic association between these two diseases remains
      unclear. This is a report on the case of a girl with severe IgA nephropathy who
      was subsequently diagnosed with subclinical Fabry's disease. An 11-year-old girl
      was admitted to our hospital with massive proteinuria and hematuria detected by
      urinary screening. An initial renal biopsy revealed severe IgA nephropathy with
      diffuse mesangial proliferation. She was treated with intravenous
      methylprednisolone pulses followed by 2 years of oral steroids. The treatment
      improved both the urinary abnormalities and the second renal biopsy findings. At
      the age of 15 years, mild proteinuria prompted us to perform a third renal
      biopsy, and histology revealed minor glomerular abnormalities. In addition,
      numerous myelin-like bodies were detected in podocytes by electron microscopy.
      The histological findings combined with the low level of alpha-galactosidase A
      activity led to the diagnosis of concomitant Fabry's disease with IgA
      nephropathy. Our experience suggests that the initial massive proteinuria was not
      due to Fabry's disease, but was rather a manifestation of coincidental IgA
      nephropathy. We speculate that the coexistence of IgA nephropathy and Fabry's
      disease occurred by chance.

PMID- 29043121
TI  - C20209T prothrombin gene mutation associated deep venous thrombosis in a
      hemodialysis patient.
AB  - Venous thromboembolism (VTE) represents the formation of a blood clot in one of
      the deep veins of human body. The significant morbidity and mortality rates
      associated with VTE have spurred increasing investigations seeking to identify
      causative factors for this complex condition. While the most frequent causes of
      an inherited hypercoagulable state are the Factor V Leiden mutation and the
      prothrombin gene mutation, polymerase chain reaction (PCR) analysis has helped to
      identify other rare causes of inherited VTE. We report a case of a recurrent deep
      venous thrombosis in an end-stage renal disease patient. All laboratory tests for
      hypercoagulable states were normal. However, PCR analysis detected a rare
      polymorphism of prothrombin gene mutation at position C20209T, instead of
      G20210A. The patient was treated successfully with a high dose of warfarin to
      maintain adequate anti-coagulation during the 2-year follow-up.

PMID- 29043122
TI  - Syndrome of inappropriate antidiuretic hormone secretion associated with
      prolonged keterolac use.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used analgesics.
      Although rare, clinicians need to keep in mind that their use may precipitate
      hyponatremia and syndrome of inappropriate antidiuretic hormone (SIADH),
      especially in high-risk patients with multiple comorbidities. In the kidneys,
      prostaglandins attenuate the water retention effect of antidiuretic hormone.
      NSAIDs cause a decrease in prostaglandins in the kidney and therefore the effect
      of ADH is potentiated. We report a case of SIADH that was associated with
      keterolac in a 65-year-old male. SIADH has not previously been reported with
      keterolac, a strong NSAID with comparable analgesic effect as morphine and
      meperidine. Keterolac may have unique properties different from other NSAIDS
      which may predispose to the development of hyponatremia. In our case, prolonged
      use of keterolac may have contributed to the development of SIADH and caution is
      needed when keterolac is used for prolonged duration. A review of the literature
      regarding development of SIADH and hyponatremia in the setting of NSAIDs is also
      presented.

PMID- 29043123
TI  - Management of streptococcal pneumoniae-induced hemolytic uremic syndrome: a case
      report.
AB  - Hemolytic uremic syndrome (HUS) secondary to Streptococcus pneumoniae infections
      (pHUS) has been well reported in the literature and accounts for roughly 5% of
      all the cases of HUS. However, this condition is likely under-diagnosed and the
      incidence is believed to be increasing. Given this increase in incidence of pHUS,
      it is important to have an understanding of the optimal means to manage the
      disease. We report a case of a 2-year-old male with pneumonia, acute kidney
      injury (AKI), microangiopathic hemolytic anemia (MAHA), and thrombocytopenia,
      diagnosed with pHUS and successfully treated with antibiotics, washed red blood
      cell (RBC) transfusions, plasma exchange (PE) with 5% albumin replacement,
      steroids, and hemodialysis. The response seen in our patient adds to the current
      literature and further supports the use of PE with albumin in patients with pHUS.

PMID- 29043124
TI  - Use of hemodialysis for the treatment of intracerebral hemorrhage in patients on
      dabigatran with normal renal function.
AB  - Dabigatran is a direct thrombin inhibitor which is approved by the Food and Drug
      Administration (FDA) for prevention of embolic stroke in patients with atrial
      fibrillation. Dabigatran has been shown to be non- inferior to warfarin in
      preventing stroke in patients with atrial fibrillation [1, 6]. The rate of major
      bleeding in patients taking dabigatran is also similar to that seen in patients
      on warfarin [1]. Unlike warfarin, there is currently no antidote available for
      reversal of anticoagulant effects of dabigatran [2, 3]. Dabigatran is excreted
      renally and accumulates in patients with acute kidney injury (AKI). Hemodialysis
      has been reported to increase clearance of dabigatran in patients with acute
      kidney injury and life-threatening bleeding [4, 5]. We present two cases of
      dabigatran-associated intracranial hemorrhage where hemodialysis was used to
      accelerate clearance of dabigatran from the blood in patients with normal renal
      function.

PMID- 29043125
TI  - Kidney biopsy for renal tubular acidosis: when tissue diagnosis makes a
      difference.
AB  - Renal tubular acidosis (RTA) is a disorder with variable presentations and
      oftentimes a nebulous underlying primary diagnosis. We describe a rare cause of
      RTA as an unusual complication of proton pump inhibitor (PPI) therapy. We report
      a case of a 33-year-old male with history of hypertension, acid reflux, allergic
      rhinitis, and low testosterone admitted with complaints of fatigue, weight loss,
      and unexplained acidosis for ~ 2 months. His medications prior to admission
      included losartan, omeprazole, potassium chloride, sildenafil, and testosterone
      propionate injections. His physical exam was unremarkable with a blood pressure
      of 120/80 mmHg. Initial lab work showed a nonanion gap metabolic acidosis with
      serum bicarbonate level of 16 mM/L and potassium 3 mM/L. Urine studies showed
      urine pH of 6.5 and a positive urine anion gap. The serum creatinine was within
      normal range(1.13 mg/dL). He required massive doses of bicarbonate and potassium
      supplementation with minimal improvement of serum chemistries achieved. The cause
      of apparent distal RTA remained elusive despite extensive blood, urine, and
      imaging testing. Ultimately a renal biopsy was obtained showing mild to moderate
      tubule-interstitial inflammation with 5% fibrosis. PPI therapy (omeprazole) was
      stopped, and he was started on prednisone 60 mg per day. Two weeks later, his RTA
      findings resolved, and he no longer required bicarbonate and potassium
      supplementation. Our case highlights the importance of recognizing a unique
      complication of RTA following PPI therapy. It also underscores the possible need
      for considering a kidney biopsy in the setting of nondiagnostic laboratory work
      up to uncover the underlying etiology of RTA and suspected allergic interstitial
      nephritis (AIN).

PMID- 29043126
TI  - Page kidney of renal allograft following blunt trauma.
AB  - We report a case of the Page kidney phenomenon which occurred in a patient with a
      renal allograft following blunt trauma. The injury occurred following an
      accidental trip resulting in a trivial fall. The patient presented with acute
      graft dysfunction with no localizing symptoms or signs. His renal function
      deteriorated further and he also became hypertensive. Serial ultrasounds showed
      an increase in the size of perinephric hematoma and evidence of renal
      compression. Prompt surgical evacuation of the hematoma was performed and renal
      function returned to baseline. Serial ultrasound examinations and timely surgical
      intervention can prevent graft loss in this unusual situation.

PMID- 29043127
TI  - Successful eculizumab treatment of recurrent postpartum atypical hemolytic uremic
      syndrome after kidney transplantation.
AB  - Postpartum atypical hemolytic uremic syndrome (aHUS) is a rare disorder
      associated with poor maternal and fetal outcomes. We describe a case of severe
      postpartum aHUS with recurrence in a kidney allograft after a second pregnancy.
      The patient had initially presented age 28 years with aHUS that developed after
      her first delivery. In spite of treatment with plasma exchange, she developed end
      stage renal disease (ESRD) requiring years of hemodialysis before receiving a
      kidney transplant from a living unrelated donor. Two years later, she became
      pregnant again and at 26 weeks gestation she presented to our hospital with
      hypertension and proteinuria. Within 48 hours of delivery she developed hemolytic
      anemia, thrombocytopenia, and oliguric acute kidney injury (AKI) culminating in
      the need for dialysis. There was no response to therapeutic plasma exchange
      (TPE). However, treatment with eculizumab led to prompt, successful resolution of
      hemolysis, thrombocytopenia, and AKI. Three months after therapy was stopped, her
      disease relapsed causing renal failure again requiring dialysis. At that time, an
      allograft biopsy revealed severe thrombotic microangiopathy (TMA). Eculizumab was
      resumed without plasma exchange leading to resolution of aHUS and return of
      kidney function. Now, her baby is nearly 2 years old. She remains on maintenance
      eculizumab therapy 1,200 mg every 2 weeks without dialysis. She has excellent
      renal function with creatinine of 1.2 mg/dL, eGFR 52 mL/min/1.73 m, and
      proteinuria 0.35 g/day. She will likely be on eculizumab for the remainder of her
      life.

PMID- 29043128
TI  - Rapid progression to end-stage renal disease in a child with a sporadic ACTN4
      mutation.
AB  - Mutations of ACTN4 cause an autosomal dominant form of focal segmental
      glomerulosclerosis (FSGS). Presentation usually occurs in the teenage years or
      later with symptoms of mild proteinuria and slowly progressive renal dysfunction
      leading to end-stage renal disease (ESRD). We report a 5-year-old female patient
      who was diagnosed with nephrotic syndrome and did not respond to 6 weeks of oral
      glucocorticoid therapy. Renal biopsy showed a collapsing variant of FSGS and
      genetic studies revealed a heterozygous disease-causing mutation in the ACTN4
      gene (c.784C>T, p.Ser262Phe). No mutations were found in the NPHS2, TRPC6, and
      INF2 genes, nor did her parents have any mutations for FSGS. She developed ESRD 6
      months after presentation. Although a disease-causing ACTN4 mutation was
      identified, the contribution of additional polymorphisms in other genes is not
      known. Such additional polymorphisms may represent yet unidentified epigenetic
      factors that contributed to the aggressive nature of this child's disease
      progression. A literature review has revealed only two similar case reports.

PMID- 29043129
TI  - Atypical case of AL amyloidosis with urinary erythrocyte casts.
AB  - We present the case of a 73-year-old man who developed an acute, severe febrile
      illness with multiorgan dysfunction, featuring renal failure, nephrotic-range
      proteinuria, microhematuria, and a skin rash. Numerous erythrocyte casts were
      found on urine microscopy. Typically, the finding of urinary erythrocyte casts
      indicates the presence of an underlying glomerular inflammatory disease. However,
      on renal biopsy, only amyloid light-chain (AL) amyloidosis and tubular injury
      were the predominant findings with no signs of glomerular or vascular
      inflammation. Photomicrographs of urinary sediment as well as renal biopsy
      histopathology of the presented case are shown. The unusual combination of
      findings, is then discussed in light of the existing literature on renal
      amyloidosis as well as erythrocyte casts in conditions other than
      glomerulonephritis.

PMID- 29043130
TI  - Anti-GBM disease after nephrectomy for xanthogranulomatous pyelonephritis in a
      patient expressing HLA DR15 major histocompatibility antigens: a case report.
AB  - Antiglomerular basement membrane (anti-GBM) antibody disease is uncommon in the
      pediatric population. There are no cases in the literature describing the
      development of anti-GBM disease following XGP or nephrectomy. We report the case
      of a 7-year-old boy with no past history of urological illness, treated with
      antimicrobials and nephrectomy for diffuse, unilateral xanthogranulomatous
      pyelonephritis (XGP). Renal function and ultrasound scan of the contralateral
      kidney postoperatively were normal. Three months later, the child represented in
      acute renal failure with rapidly progressive glomerulonephritis requiring
      hemodialysis. Renal biopsy showed severe crescentic glomerulonephritis with 95%
      of glomeruli demonstrating circumferential cellular crescents. Strong linear IgG
      staining of the glomerular basement membranes was present, in keeping with anti
      GBM disease. Circulating anti-GBM antibodies were positive. Treatment with plasma
      exchange, methylprednisolone, and cyclophosphamide led to normalization of anti
      GBM antibody titers. Frequency of hemodialysis was reduced as renal function
      improved, and he is currently independent of dialysis with estimated glomerular
      filtration rate 20.7 mls/min/1.73 m2. Case studies in the adult literature have
      reported the development of a rapidly progressive anti-GBM antibody-induced
      glomerulonephritis following renal surgery where patients expressed HLA DR2/HLA
      DR15 major histocompatibility (MHC) antigens. Of note, our patient also expresses
      the HLA DR15 MHC antigen.

PMID- 29043132
TI  - Antineutrophil cytoplasmic antibody mediated glomerulonephritis associated with
      levamisole-adulterated cocaine.
AB  - Levamisole-adulterated cocaine has increased in prevalence over the last decade
      and is known to be associated with antineutrophil cytoplasmic antibodies (ANCA).
      Dermatologic manifestations of levamisole exposure, including cutaneous
      vasculitis, are widely appreciated; less is known about its effects on the
      kidney. We report two cases of patients with a history of cocaine abuse and
      levamisole-induced cutaneous vasculitis, who developed acute kidney injury in the
      setting of elevated ANCA titers. Renal biopsies of both revealed pauci-immune
      complex glomerulonephritis with diffuse crescentic disease. These cases
      demonstrate a rare but serious complication of long-term cocaine use.

PMID- 29043131
TI  - Potential association between membranous nephropathy and sargramostim therapy for
      pulmonary alveolar proteinosis.
AB  - We present the case of a 43-year-old woman with a diagnosis of pulmonary alveolar
      proteinosis, on chronic treatment with sargramostim, a recombinant granulocyte
      macrophage colony-stimulating factor, who presented with the nephrotic syndrome
      secondary to biopsy-proven membranous nephropathy. We discuss potential
      underlying mechanisms, including speculated effects of sargramostim on mesangial
      cells and the kidney resident macrophages, and review the existing literature on
      the potential association between these two disorders.

PMID- 29043133
TI  - Lysozyme amyloidosis - a case report and review of the literature.
AB  - Lysozyme amyloidosis is an exceedingly rare hereditary autosomal dominant
      amyloidosis, which is characterized by the precipitation of lysozyme protein
      within the body, leading to multi-organ dysfunction. Herein, we present the case
      of a U.S. family affected by lysozyme amyloidosis. In particular, we report
      pericardial disease involvement leading to recurrent pericardial effusion, which
      to our knowledge has not been described yet. To our knowledge, we have also for
      the first time identified the amyloidogenic component of lysozyme amyloidosis via
      laser microdissection and mass spectrometry from a bone marrow biopsy. The
      diagnosis of this disease remains challenging as it can be easily mistaken for
      primary amyloidosis, which also presents with similar symptoms.
      Immunohistochemical staining of tissue for specific amyloidogenic proteins allows
      for an accurate diagnosis and should be performed in all amyloidosis patients in
      order to spare patients from potentially futile or harmful therapy. The
      widespread systemic involvement of lysozyme amyloidosis currently provides
      limited options for treatment, although kidney and/or liver transplantation
      appear to be promising palliative treatments. Practicing clinicians and
      researchers need to collect more information about this rare entity to further
      characterize the behavior of this disease and develop new potential treatment
      strategies.

PMID- 29043134
TI  - Cryoglobulinemic membranoproliferative glomerulonephritis associated with mucosa
      associated lymphoid tissue lymphoma treated with rituximab.
AB  - Cryoglobulinemia and mucosa-associated lymphoid tissue (MALT) lymphoma are
      diseases characterized by B-cell dysregulation and overproduction of antibodies.
      Vasculitis and cutaneous manifestations are common, but renal involvement is
      rare. A 65-year-old woman with type 1 cryoglobulinemia and MALT lymphomas of the
      right lacrimal and parotid glands successfully treated by excision and
      chemoradiotherapy, presented with dyspnea on exertion, edema, and hematuria.
      Renal biopsy findings revealed type 1 cryoglobulinemic glomerulonephritis. She
      underwent treatment with high-dose oral prednisone and intravenous rituximab with
      subsequent return of creatinine to baseline levels. To our knowledge, this is the
      first report of a patient in whom type 1 cryoglobulinemia, multiple MALT
      lymphomas, and MPGN with IgM cryoglobulin deposits coexist. Evidence for
      rituximab is sparse with widely varying protocols and mixed results. There is a
      need for high quality evidence in the treatment of these conditions.

PMID- 29043135
TI  - Crescentic glomerulonephritis with dual positive anti-GBM and C-ANCA/PR3
      antibodies.
AB  - Antiglomerular basement membrane (anti-GBM) antibodies are more often accompanied
      by myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) than by
      proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA). Both disease
      processes can affect the kidneys and/or the lungs. Patients with dual positive
      disease may have an atypical presentation which may delay diagnosis and
      treatment. Here we report a case of crescentic glomerulonephritis associated with
      positive PR3-ANCA and anti-GBM antibodies who underwent both lung and kidney
      biopsies.

PMID- 29043136
TI  - Collapsing glomerulopathy associated with hemophagocytic syndrome in a patient
      with NK/T cell lymphoma.
AB  - Hemophagocytic syndrome (HPS) is a rare condition caused by dysregulated
      activation of the immune system leading to infiltration of bone marrow and organs
      by nonmalignant macrophages that phagocytose blood cells. Primary HPS is caused
      by inherited immune dysregulation whereas secondary HPS is triggered by
      neoplastic, infectious or autoimmune diseases. Clinically, the syndrome presents
      with continuous high-grade fever in association with multi-organ involvement. Few
      data are available regarding renal manifestations of HPS. We report a 60-year-old
      patient with NK/T cell nasopharyngeal extranodal lymphoma who presented with
      acute kidney injury and nephrotic range proteinuria in association with fever and
      pancytopenia. A kidney biopsy was consistent with collapsing glomerulopathy. A
      final diagnosis of HPS was made on the basis of clinical, laboratory, and bone
      marrow biopsy findings in accordance with established diagnostic criteria.
      Steroid therapy was initiated. However, the patient failed to recover his renal
      function and remained hemodialysis-dependent. Key diagnostic and therapeutic
      challenges and strategies used to overcome those challenges are discussed.

PMID- 29043137
TI  - Tenofovir and kidney transplantation: case report.
AB  - BACKGROUND: Hepatitis B viral infection (HBV) has been regarded as a
      contraindication for kidney transplantation because of the high risk of viral
      activation induced by immunosuppressive therapy. Anti-retroviral drugs have
      changed the prognosis of patients with hepatitis B viral infection (HBV+) who are
      candidates for renal transplant; indeed, therapy with antiretroviral drugs may
      ensure lower rates of morbidity and mortality compared to traditional therapies.
      Entecavir is the first-line antiviral therapy recommended for the treatment of
      HBV+ kidney-transplanted patients. In case of resistance to entecavir, tenofovir
      may be an alternative drug, either alone or in combination with entecavir.
      However, the best strategy of treatment is still unknown. In this case-report, a
      HBV+ kidney-transplanted patient who presented resistance to entecavir was
      initially treated by associating tenofovir to entecavir and with tenofovir alone
      afterward. This strategy induced complete remission of viral replication. CASE
      PRESENTATION: In a HBV+ kidney-transplanted patient under monotherapy with
      entecavir, HBV flare (HBV DNA > 170.000 * 103 UI/mL, HBeAg+, HbeAb-) occurred 9
      months after transplantation; at that time, blood chemistry highlighted:
      creatinine 1.46 mg/dL, blood urea 65 mg/dL, e-GFR 50 mL/min, proteinuria 300
      mg/24 h, calciuria 2,12 mmol/24 h, phosphaturia 0.56 g/24 h, vitamin D 11.5
      ng/mL, PTH 130 pg/mL, calcemia 2.3 mmol/L, and phosphoremia 2 mg/dL. Liver
      elastometry (FibroScan) showed moderate fibrosis. Tenofovir was associated to
      entecavir. Three months after the combination therapy, reduction in HBV DNA
      replication (351 * 103 UI/mL) was obtained. Creatinine and e-GFR were 1.48 mg/dL
      and 52 mL/min, respectively. At this point, entecavir was discontinued. After 13
      months of tenofovir monotherapy, complete remission of viral replication was
      achieved but renal function deteriorated and proteinuria increased. CONCLUSION:
      This case-report indicates that tenofovir is effective in reducing viral
      replication of hepatitis B virus in a kidney-transplanted patient who presented
      resistance to previous treatment with entecavir. However, it should be taken into
      account that tenofovir could affect renal function.

PMID- 29043138
TI  - Coexistence of atypical hemolytic uremic syndrome and crescentic IgA nephropathy
      treated with eculizumab: a case report.
AB  - Rapid progression to end-stage renal disease has been reported in a minority of
      patients with immunoglobulin A (IgA) nephropathy. In particular, crescentic IgA
      nephropathy has a poor prognosis in patients with a higher initial serum
      creatinine level. The complement system plays an important role in the
      pathogenesis of crescentic IgA nephropathy. Atypical hemolytic uremic syndrome
      (aHUS), which is characterized by thrombotic microangiopathy, is distinct from
      Shigatoxin-induced HUS and thrombotic thrombocytopenic purpura. aHUS is
      associated with dysregulation of the alternative complement system. Eculizumab,
      an anti-C5 antibody, is effective in limiting complement activation in patients
      with paroxysmal nocturnal hemoglobinuria, aHUS, or refractory IgA nephropathy in
      some case reports. We herein report the case of a 42-year-old man with acute
      kidney injury (AKI) clinically and histologically diagnosed with the coexistence
      of aHUS and crescentic IgA nephropathy. The patient was treated with steroids,
      plasmapheresis, and hemodialysis; however, eculizumab treatment was initiated on
      hospital day 21 due to resistance to and dependence on the conventional
      aggressive therapy. Clinical remission of aHUS was achieved on day 70, but the
      renal function failed to recover from dialysis dependence. To the best of our
      knowledge, this is the first report showing the clinical course of a refractory
      patient with the coexistence of aHUS and crescentic IgA nephropathy treated with
      eculizumab. This case highlights the clinical importance of early diagnosis and
      appropriate initiation of eculizumab for the treatment of this type of AKI.

PMID- 29043139
TI  - Primary renal lymphoma: an unusual finding following radical nephrectomy.
AB  - Secondary kidney involvement by disseminated non-Hodgkin's lymphoma (NHL) is
      quite common and is estimated to approach 30 - 60% in NHL patients. However,
      primary renal lymphoma is exceedingly rare and estimated to make up less than 1%
      of all kidney masses. We report a case of primary renal NHL presenting with
      profound hypercalcemia and renal failure recalcitrant to medical management,
      ultimately treated with urgent radical nephrectomy. To our knowledge, this is the
      first report of primary renal lymphoma presenting in this acute fashion.

PMID- 29043140
TI  - Warfarin-related nephropathy in a patient with renal pelvic cancer.
AB  - An 83-year-old Japanese man had a history of chronic heart failure due to
      bradycardia-tachycardia syndrome. He was admitted to our hospital because of
      macrohematuria and acute kidney injury (AKI), which were detected by an urologist
      at an outpatient visit. He had a history of recurrent macrohematuria and
      transurethral resection of bladder tumors twice in the preceding 2 years. He had
      been on warfarin for 12 years, with a stable international normalized ratio (INR)
      that was usually less than 2.1. Urinalysis revealed numerous red blood cells
      (RBCs) and mild proteinuria without RBC casts. His serum creatinine level was
      elevated to 2.41 mg/dL from 0.96 mg/dL at 3 weeks before admission. INR was 1.44.
      Hydronephrosis was not observed. Ureteroscopy detected invasive urothelial
      carcinoma of the renal pelvis, and right laparoscopic nephroureterectomy was
      performed at 41 days after diagnosis of AKI. The background renal parenchyma
      displayed tubular obstruction by red blood cell casts and acute tubular injury,
      which were changes compatible with warfarin-related nephropathy (WRN). Warfarin
      was discontinued, and the serum creatinine level recovered to 1.66 mg/dL after 3
      months. In the present patient with nephrosclerosis, WRN occurred at a
      therapeutic INR level after 12 years of uneventful warfarin therapy, and the
      coexisting urothelial malignancy was a unique feature.

PMID- 29043141
TI  - Antineutrophil cytoplasmic antibody-positive pauci-immune glomerulonephritis
      associated with mantle cell lymphoma.
AB  - Renal involvement in non-Hodgkin lymphoma, especially mantle cell lymphoma (MCL)
      is rare. A 77-year-old man presented with acute kidney injury (AKI), which
      rapidly progressed to dialysis dependence. Kidney biopsy revealed patchy B-cell
      lymphocytic aggregates in the interstitium, which were positive for cyclin D1,
      consistent with atypical CD5-negative MCL as confirmed by the detection of
      translocation t(11;14) by FISH. Crescents were noted in 3 of 26 glomeruli; while
      PR-3 antineutrophil cytoplasmic antibody (ANCA) positivity and negative
      immunofluorescence suggested an additional pauci-immune (rapidly progressive)
      glomerulonephritis pattern of injury. Patient received chemotherapy
      (cyclophosphamide, vincristine, and prednisone), which improved his renal
      function and allowed for discontinuation of hemodialysis. However, he died from
      pulmonary hemorrhage 8 months after initial presentation. This is the first
      reported case of a patient with coexistence of renal MCL infiltration and ANCA
      positive pauci-immune glomerulonephritis.

PMID- 29043142
TI  - Costimulation pathway blockade in kidney transplant recipients with de-novo
      rheumatoid arthritis.
AB  - The best approach to treatment of de-novo rheumatoid arthritis in solid organ
      transplant recipients on typical immunosuppression is not well established. The
      use of biologics targeting specific cell types, cytokines, and immunological
      pathways has been gaining interest in the treatment of both, auto- and
      alloimmunity. We present a case of de-novo rheumatoid arthritis in a kidney
      transplant recipient 10 years post-transplant while receiving cyclosporine,
      mycophenolate mofetil, and also prednisone. Initial presentation included
      features of polymyalgia rheumatica and nephrotic range proteinuria. Kidney biopsy
      showed membranous nephropathy. The patient was initially treated with
      methotrexate, while mycophenolate mofetil was discontinued. Clinical symptoms
      improved, but creatinine significantly increased, which led to discontinuation of
      methotrexate and mycophenolate mofetil was restarted. The kidney function
      improved, but the patient experienced a flare of rheumatoid arthritis.
      Costimulatory blocker, abatacept, was initiated and cyclosporine was gradually
      tapered off. Graft function remained stable for a follow-up period of 7 years.
      Joint pain, weakness, and stiffness resolved. Follow-up plain film radiographs at
      5 years post initial presentation showed no new joint erosions in hands or feet.
      Costimulatory blockers may broaden the therapeutic choices of transplant
      recipients with de-novo autoimmune diseases.

PMID- 29043143
TI  - Focal segmental glomerulosclerosis associated with mitochondrial disease.
AB  - Primary mitochondrial diseases (MD) are complex, heterogeneous inherited diseases
      caused by mutations in either the mitochondrial or nuclear DNA. Glomerular
      diseases in MD have been reported with tRNA mutation m.3243A>G causing a syndrome
      of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes
      (MELAS). We describe here a case of focal segmental glomerulosclerosis (FSGS)
      associated with a new tRNA mutation site. A 34-year-old man with a history of
      living related kidney transplantation, diabetes, hearing loss, and developmental
      delay presented to the outpatient clinic with complaints of new behavioral
      difficulties, worsening symptoms, and brain involvement on imaging. Physical
      examination was remarkable for difficulty hearing, a pattern of dysarthric
      speech, and cerebellar gait. Laboratory investigations including lactate levels
      were unremarkable. Based on this set of clinical circumstances, concern for an
      underlying genetic abnormality was raised. Multiple metabolic tests were
      unremarkable. Whole exome sequencing revealed a mitochondrial MT-TW tRNA change
      at position m.5538G>A. Genotype-phenotype correlations are consistent with this
      tRNA mutation as a cause of his symptoms. To the best of our knowledge, this is
      the first case describing FSGS-associated MD caused by an m.5538 G>A mutation.
      Consideration of an underlying MD should be made in patients presenting with
      deafness, neurologic changes, diabetes, and renal failure.

PMID- 29043144
TI  - Plasmapheresis for treatment of immune complex-mediated glomerulonephritis in
      infective endocarditis: a case report and literature review.
AB  - We report the case of a 57-year-old man who presented with subacute bacterial
      endocarditis secondary to Streptococcus mutans complicated by biopsy-proven
      immune complex-mediated glomerulonephritis (ICGN). Despite initial treatment with
      antibiotics and a short course of corticosteroids, the kidney function further
      deteriorated, and plasmapheresis was introduced as third-line therapy to remove
      circulating immune complexes. Following 7 treatment sessions, the patient
      recovered kidney function. We discuss the potential merit of plasmapheresis for
      patients with subacute bacterial endocarditis who develop ICGN.

PMID- 29043145
TI  - ANCA-associated pauci-immune glomerulonephritis in a patient with bacterial
      endocarditis: a challenging clinical dilemma.
AB  - PURPOSE: We report the case of a 59-year-old man with chronic hepatitis B and C
      infection presenting with acute kidney injury and enterococcus faecalis-infective
      endocarditis (IE). An elevated proteinase-3 (PR3)-ANCA and pauci-immune
      glomerulonephritis (GN) on renal biopsy were discovered, corresponding to ANCA
      mediated GN. We conducted a literature review to assess the role of ANCA in IE
      and treatment implications. METHODS: On systematic review of the literature, we
      found five previous cases whereby IE caused by streptococcus and bartonella
      species were related to ANCA vasculitis-associated GN. RESULTS: Most reports of
      IE-related GN are mediated by immune complex deposition and resolve following
      microbial clearance. Of the 5 cases of ANCA GN in the setting of IE, all had
      markedly elevated levels of PR3-ANCA with either a subacute or chronic course of
      infection. Patients were treated with a combination of steroids and
      cyclophosphamide (2/5), steroids and antibiotics alone (1/5), or with valvular
      replacement (2/5). Renal function was recovered in 4/5 patients. CONCLUSION:
      Infection is a major etiologic player in the formation of ANCA; however, the role
      of PR3-ANCA in IE remains unclear. Kidney biopsy is essential in differentiating
      IE-related GN due to infection and immune complex deposition versus ANCA
      associated vasculitis. A paucity of reports on the development of GN in IE
      associated ANCA vasculitis exists, highlighting the rarity of our case and lack
      of clear therapeutic strategies in a patient with active infection requiring
      immunosuppression. In this case, the patient's chronic hepatitis B and C
      coinfection presented a unique challenge.

PMID- 29043146
TI  - Calciphylaxis in a nondialysis patient treated with sodium thiosulfate and high
      dose of oxygen.
AB  - BACKGROUND: Calciphylaxis in a nondialysis patient is a rare condition and is
      characterized by calcific deposition in tissue. We present a case of
      calciphylaxis in a nondialysis patient who was diagnosed by clinical presentation
      and skin biopsy and was treated with sodium thiosulfate with improvement of skin
      lesions. CASE: A 43-year-old female with type 2 diabetes and atrial fibrillation
      taking oral anticoagulation medication presented with reddish drainage from the
      right buttock. On physical examination, a large perirectal abscess overlying
      necrosis was found. She also developed acute kidney injury with creatinine of 3.7
      mg/dL at peak from 0.8 mg/dL at baseline. She received antibiotics intravenously
      and wound debridement. During hospitalization, she developed areas of numerous
      painful erythematous lesions with central dusky necrosis on bilateral lower
      extremities. Punch biopsy was done, which initially revealed small-vessel
      vasculitis. However, those lesions did not respond to steroid therapy. A second
      biopsy was done showing extensive fat necrosis and medial calcification of vessel
      walls consistent with calciphylaxis. She was treated with high-flow oxygen and
      sodium thiosulfate intralesionally and intravenously for 6 months. The lesions
      remarkably reduced in size and were less painful on follow-up. CONCLUSION: High
      dose oxygen and sodium thiosulfate could potentially be effective treatments for
      calciphylaxis in nondialysis patients.

PMID- 29043147
TI  - A case report of paraproteinemia-associated pauci-immune glomerulonephritis - a
      new form of monoclonal gammopathy of renal significance?
AB  - BACKGROUND: Renal disease associated with paraproteinemias is classically
      predicated upon pathologic paraprotein deposition in the kidney. However, growing
      evidence suggests that paraproteins may be able to systemically activate
      complement or neutrophils to drive renal damage. This may provide an alternative
      pathologic mechanism for renal injury in rare cases. CASE REPORT: We report a
      case of a patient with crescentic pauci-immune glomerulonephritis presenting with
      rapidly progressive renal failure, polyarthropathy, and a purpuric rash in
      association with a monoclonal immunoglobulin G kappa-light-chain producing
      multiple myeloma. Serum anti-neutrophil cytoplasmic antibodies were not detected.
      Kidney biopsy, including with Pronase digestion, did not reveal pathologic
      paraprotein deposition. Two previously published similar case reports are also
      discussed. CONCLUSION: We propose a novel pathologic mechanism involving
      monoclonal proteins as a trigger for pauci-immune glomerulonephritis, potentially
      via complement dysregulation and/or neutrophil activation. This requires further
      epidemiologic and mechanistic study.

PMID- 29043148
TI  - Membranoproliferative glomerulonephritis associated with Rosai-Dorfman disease.
AB  - Rosai-Dorfman disease is also known as sinus histiocytosis with massive
      lymphadenopathy. Extranodal Rosai-Dorfman disease has been reported in ~ 43% of
      cases; the most frequent extranodal sites - skin, soft tissue, bone, respiratory
      tract, and eye - are usually involved in association with lymphadenopathy. Lack
      of lymph node involvement is rare, especially when patients manifest renal
      disease. Here, we describe a patient who developed membranoproliferative
      glomerulonephritis when lymphadenopathy was absent. During follow-up for sinus
      histiocytosis, a 7-year-old Japanese boy developed proteinuria and hematuria. No
      renal abnormality was present in ultrasound imaging. Histologic examination of a
      renal biopsy specimen disclosed moderate mesangial proliferation, focal
      thickening of glomerular capillary walls, and mesangial interposition.
      Mononuclear cells infiltrated the interstitium. Immunofluorescence showed intense
      IgG, C3, and C4 reactivity in portions of the mesangium and glomerular capillary
      walls. Electron microscopy depicted nodular deposits in mesangial, endocapillary,
      and subepithelial areas. Immunohistochemistry for S-100 protein, CD68, and
      lysozyme was positive within the interstitium. CD1a staining was absent. These
      findings were diagnostic for membranoproliferative glomerulonephritis. Multidrug
      therapy, including methylprednisolone and mizoribine, improved urinary findings
      and induced complete remission of both diseases. To the best of our knowledge,
      this is the first report of Rosai-Dorfman disease complicated by renal disease in
      the absence of concurrent nodal involvement. Clinicians should be alert to this
      diagnostic possibility.

PMID- 29043149
TI  - Pre-B acute lymphoblastic leukemia with t(1;19) in an adult initially presenting
      as hematuria and bilateral renal enlargement: a case report and literature
      review.
AB  - Although pre-B acute lymphoblastic leukemia (ALL) is the most common type of
      renal leukemic infiltration; the renal infiltration with leukemia cells as the
      initial manifestation of leukemia is very rare. Translocation (1;19)(q23;p13) is
      one of the most common chromosomal abnormalities in patients with ALL and is
      observed in 5 - 6% of children with pre-B ALL. However, the incidence of t(1;19)
      in adults is lower, not exceeding 3%, and the prognosis of adult patients is
      usually poor. Herein, we report a 52-year-old female patient with pre-B ALL who
      initially presented as bilateral renal enlargement. The cytogenetic analysis
      revealed chromosomal abnormalities including t(1;19). The patient underwent three
      consecutive courses of chemotherapy with VDLP (vincristine, daunorubicin, L-asp,
      and prednisolone) and gained a short complete remission. Her kidneys recovered to
      normal size, and renal function returned to normal level. However, after complete
      remission for only 3 months, the patient exhibited resistance to consolidation
      chemotherapy and indicated evidence of marrow relapse. Although we increased the
      drug dosage and attempted to use a different protocol, she died of severe anemia
      and hemorrhage almost 10 months after she was first admitted. In conclusion, pre
      B cell ALL is the most common type of leukemia to present with renal infiltration
      as the presenting sign. Because of the poor outcome of ALL, some new therapeutic
      approaches may improve the patients' conditions.

PMID- 29043150
TI  - Community-acquired pneumonia in the United Kingdom: a call to action.
AB  - Pneumococcal disease has a high burden in adults in the United Kingdom (UK);
      however, the total burden is underestimated, principally because most cases of
      community-acquired pneumonia (CAP) are non-invasive. Research into pneumonia
      receives poor funding relative to its disease burden (global mortality,
      disability-adjusted life years, and years lived with disability), ranking just 20
      out of 25 for investment in infectious diseases in the UK. The current accuracy
      of data for establishing incidence rates is questionable, and it is a reflection
      of the paucity of research that much of the background information available
      derives from nearly 30 years ago. Given the relationship between CAP and
      mortality (pneumonia accounts for 29,000 deaths per annum in the UK, and 5-15% of
      patients hospitalised with CAP die within 30 days of admission), and the
      increasing threat of antimicrobial resistance associated with inappropriate
      antibiotic prescribing, such neglect of a highly prevalent problem is concerning.
      In this Call to Action, we explore the poorly understood burden of CAP in the UK,
      discuss the importance of an accurate diagnosis and appropriate treatment, and
      suggest how national collaboration could improve the management of an often life
      threatening, yet potentially preventable disease.

PMID- 29043152
TI  - Tattoos as a window to the psyche: How talking about skin art can inform
      psychiatric practice.
AB  - Tattooing the skin as a means of personal expression is a ritualized practice
      that has been around for centuries across many different cultures. Accordingly,
      the symbolic meaning of tattoos has evolved over time and is highly
      individualized, from both the internal perspective of the wearer and the external
      perspective of an observer. Within modern Western societies through the 1970s,
      tattoos represented a cultural taboo, typically associated with those outside of
      the mainstream such as soldiers, incarcerated criminals, gang members, and others
      belonging to marginalized and counter-cultural groups. This paper aims to review
      the more recent epidemiology of tattoos in Western culture in order to establish
      that tattooing has become a mainstream phenomenon. We then review psychological
      and psychiatric aspects of tattoos, with a goal of revising outmoded stigmas
      about tattooing and helping clinicians working with tattooed patients to
      facilitate an exploration of the personal meaning of skin art and self-identity.
      We suggest that as a kind of augmentation of the physical exam, looking at and
      talking to patients about their tattoos can provide a valuable window into the
      psyche, informing clinical practice.

PMID- 29043153
TI  - Developmental psychopathology: A primer for clinical pediatrics.
AB  - Developmental psychopathology (DP), broadly defined as the scientific discipline
      that has as its primary goal the integration of developmental science and
      psychopathology into a coherent approach to explanatory models for
      psychopathological development, has become the dominant approach in the past
      decade for understanding the origins of mental disorders among children and
      adolescents. Hence, it is incumbent upon those working in the field of clinical
      pediatrics to have at least a basic understanding of its core principles of DP.
      This article provided such an understanding (i.e., a primer) in an exposition of
      the four principles that are generally considered be core elements of with
      examples illustrative of each of the principles.

PMID- 29043151
TI  - Biobehavioral assessment of the anxiety disorders: Current progress and future
      directions.
AB  - It is difficult to accurately assess and differentially diagnose the anxiety
      disorders. The current system of assessment relies heavily on the subjective
      measures of client self-report, clinical observation, and clinical judgment.
      Fortunately, recent technological advances may enable practitioners to utilize
      objective, biobehavioral measures of assessment in a clinical setting. The
      current body of literature on two of these biobehavioral tools (eye-tracking and
      electrocardiogram devices) is promising, but more validation and standardization
      research is needed to maximize the utility of these devices. Eye-tracking devices
      are uniquely capable of providing data that can be used to differentially
      diagnose anxiety disorders from both other commonly comorbid and misdiagnosed
      disorders. Both eye-tracking and electrocardiogram devices are able to provide
      change-sensitive assessment information. This objective, real-time feedback can
      assist clinicians and researchers in assessing treatment efficacy and symptom
      fluctuation. Recently developed wearable and highly portable electrocardiogram
      devices, like the wearable fitness and behavior tracking devices used by many
      consumers, may be particularly suited for providing this feedback to clinicians.
      Utilizing these biobehavioral devices would supply an objective, dimensional
      component to the current categorical diagnostic assessment system. We posit that
      if adequate funding and attention are directed at this area of research, it could
      revolutionize diagnostic and on-going assessment practices and, in doing so,
      bring the field of diagnosis out of the 20th century.

PMID- 29043154
TI  - Taking care of suicidal patients with new technologies and reaching-out means in
      the post-discharge period.
AB  - Suicide is a global public health problem with over one million people dying by
      suicide each year worldwide. Research efforts have focused on developing and
      testing novel suicide prevention strategies employing recent technological
      advances. In order to provide a review regarding the role of new technologies
      (e.g., postcards/letters, text messages, crisis cards, telephone contacts, online
      interventions) in suicide prevention, we searched PubMed, ScienceDirect,
      ResearchGate, and Crisis to identify all papers in English from 1977 to 2016. Our
      results indicated that brief contact interventions show promise in reducing the
      number of episodes of repeated self-harm and/or suicide attempts following
      discharge from the Emergency Department or psychiatric units. Innovative methods
      of contact (e.g., text messages) are easily implemented by clinicians and
      received by patients in the period of post discharge and have been shown to be
      beneficial. However, more research employing randomized clinical trials
      investigating the potential benefits of these novel suicide prevention methods is
      warranted. Future researchers should continue improving and testing new
      technologies in the prevention of suicide.

PMID- 29043155
TI  - Catatonia as a putative nosological entity: A historical sketch.
AB  - Kahlbaum was the first to propose catatonia as a separate disease following the
      example of general paresis of the insane, which served as a model for
      establishing a nosological entity. However, Kahlbaum was uncertain about the
      nosological position of catatonia and considered it a syndrome, or "a temporary
      stage or a part of a complex picture of various disease forms". Until recently,
      the issue of catatonia as a separate diagnostic category was not entertained,
      mainly due to a misinterpretation of Kraepelin's influential views on catatonia
      as a subtype of schizophrenia. Kraepelin concluded that patients presenting with
      persistent catatonic symptoms, which he called "genuine catatonic morbid
      symptoms", particularly including negativism, bizarre mannerisms, and
      stereotypes, had a poor prognosis similar to those of paranoid and hebephrenic
      presentations. Accordingly, catatonia was classified as a subtype of dementia
      praecox/schizophrenia. Despite Kraepelin's influence on psychiatric nosology
      throughout the 20th century, there have only been isolated attempts to describe
      and classify catatonia outside of the Kraepelinian system. For example, the
      Wernicke-Kleist-Leonhard school attempted to comprehensively elucidate the
      complexities of psychomotor disturbances associated with major psychoses.
      However, the Leonhardian categories have never been subjected to the scrutiny of
      modern investigations. The first three editions of the DSM included the narrow
      and simplified version of Kraepelin's catatonia concept. Recent developments in
      catatonia research are reflected in DSM-5, which includes three diagnostic
      categories: Catatonic Disorder due to Another Medical Condition, Catatonia
      Associated with another Mental Disorder (Catatonia Specifier), and Unspecified
      Catatonia. Additionally, the traditional category of catatonic schizophrenia has
      been deleted. The Unspecified Catatonia category could encourage research
      exploring catatonia as an independent diagnostic entity.

PMID- 29043156
TI  - Transition to school for children with autism spectrum disorder: A systematic
      review.
AB  - AIM: To identify factors that promote a positive start to school for children
      with autism spectrum disorder (ASD). METHODS: Web of Science, MEDLINE, Scopus,
      and PsychINFO searches were conducted to identify literature published after 1991
      and relevant to school transition processes in children with ASD. Twenty studies
      were deemed eligible for inclusion. These studies evaluated a range of factors
      including school readiness, parent and teacher perspectives on transition
      practices, characteristics of children with ASD that are associated with
      successful transition to school and the impact of school based intervention
      programs. RESULTS: A review of these studies showed that children with ASD are
      less school ready emotionally than their peers and those children with ASD appear
      to have more externalising behaviours and self-regulation difficulties that
      affect their school engagement and their relationships with their teachers. There
      was a paucity of research looking at interventions targeting school readiness.
      However, school-based behavioural interventions appear to improve cognitive,
      language and daily living skills, but have less impact on socialisation and peer
      inclusion. CONCLUSION: Children with ASD face more challenges transitioning to
      school, particularly with social interaction. Further development and
      implementation of specific school-based interventions is needed in order to
      assist children with autism to maximise their success in starting school.

PMID- 29043157
TI  - Cardiac troponin T quantitative assay failure as a result of antibody
      interference.
AB  - BACKGROUND: Immunoassays are prone to interference by various substances which
      may cause inaccurate results. This type of interference is difficult to detect
      analytically. OBJECTIVE: A case of CARDIAC Troponin T Quantitative reader (Roche
      Diagnostics) assay failure was detected and investigated in order to ascertain
      the likely cause. METHOD: Patient whole blood was mixed with cardiac troponin T
      positive blood, patient and control sera were denuded of immunoglobulin G by
      protein A-affinity chromatography and patient sera were mixed with mouse serum.
      Samples were analysed on a CARDIAC Troponin T Quantitative reader. RESULTS: A
      mixture of patient whole blood and cardiac troponin T-positive blood resulted in
      assay failure; removal of immunoglobulin G from patient sera reversed the cardiac
      troponin T assay failure; the addition of mouse serum as a heterophile antibody
      blocking agent had no effect. CONCLUSION: It is proposed that the interference
      resulting in assay failure may not be because of a heterophile antibody, but
      rather a result of a circulating autoantibody to cardiac troponin T, which may
      compete with antibody assay reagents for binding sites.

PMID- 29043158
TI  - Heterogeneity of Campylobacter species isolated from serial stool specimens of
      Egyptian children using pulsed field gel electrophoresis.
AB  - BACKGROUND: The genus Campylobacter spp. is a common cause of human acute
      bacterial enteritis and travellers' diarrhoea worldwide. OBJECTIVE: To determine
      whether multiple serial isolations of Campylobacter spp., when obtained from a
      single child, represented the same or a different organism. METHODS: In a birth
      cohort study conducted in Egypt, numerous children showed serial isolations of
      Campylobacter spp. Of these, 13 children were selected from different households
      based on the successive isolation of six or more Campylobacter isolates from
      stool samples. RESULTS: Eighty isolates were recovered and identified as either
      Campylobacter coli (n = 25) or Campylobacter jejuni (n = 55). Pulsed-field gel
      electrophoresis (PFGE) revealed the presence of 38 unique C. jejuni and 24 C.
      coli profiles at a similarity level of >= 90%. Although no serially-identical
      isolates were detected in six children, others demonstrated at least one
      identical couple of isolates; all identified serially between one to six weeks.
      Two children demonstrated > 80% similar couples of isolates that appeared seven
      months apart. PFGE could be a useful tool for differentiating reinfection,
      relapse and convalescent excretion phases. CONCLUSION: Our data suggest that
      Campylobacter infection in children is a complex process; children are exposed to
      multiple species in endemic environments and strains of the same bacterium appear
      to be shed serially between one to six weeks after the first exposure. Isolates
      that persisted for longer periods were relatively less similar, as shown from the
      results of this study.

PMID- 29043159
TI  - The association between sex hormone-binding globulin and type 2 diabetes in
      Nigerian men.
AB  - BACKGROUND: Epidemiological studies have shown that sex hormone-binding globulin
      (SHBG) has a role in glucose homeostasis in both men and women. However, a
      prospective study on Japanese-American subjects concluded that SHBG was not a
      significant risk factor in either men or women, suggesting ethnic differences. We
      were not aware of any evaluation of SHBG in subjects of African ancestry.
      OBJECTIVES: We investigated the association between SHBG and insulin resistance
      in type 2 diabetic diabetic men in a hospital in Nigeria. METHOD: Forty-eight
      male subjects with type 2 diabetes and 20 non-diabetic male subjects were
      recruited in this cross-sectional hospital-based study by the convenient sampling
      method. Height and circumferences around the waist and hip were measured to the
      nearest 0.5 cm and the waist-hip ratio was calculated from this measurement.
      Weight was measured and body mass index was calculated. Fasting plasma glucose
      concentration was measured by the glucose oxidase method with a between-run
      coefficient of variation of 3%. Insulin and SHBG were measured by means of enzyme
      linked immunosorbent assay (ELISA). RESULTS: There was a statistically
      significant difference between test results for the diabetic and non-diabetic
      patients. The mean SHBG concentration was higher in the non-diabetic group (42.2
      nmol/L) than the diabetic group (30.5 nmol/L). A significant inverse association
      between insulin resistance and SHBG was observed (r = 0.353, p < 0.015).
      CONCLUSION: This study supported earlier observations that a significant inverse
      correlation exists between SHBG and insulin resistance and provides evidence that
      the relationship may extend to type 2 diabetic men of African ancestry in
      Nigeria.

PMID- 29043160
TI  - Carriage rate and serotypes of Streptococcus pneumoniae amongst children in Thika
      Hospital, Kenya.
AB  - Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide.
      Rates of carriage are highest in infants and the elderly. The objectives of this
      study were to determine the rate of nasopharyngeal colonization by S. pneumoniae,
      and to describe the antibiotic resistant patterns and the serotypes of the
      carried isolates. A cross-sectional study design was used. Nasopharyngeal swabs
      were collected from 315 children in the months of October and November 2010 and
      processed to isolate S. pneumoniae. The isolates were serotyped by the Quellung
      reaction and their antibiotic susceptibilities assessed by the disc diffusion
      method. The overall nasopharyngeal carriage rate for S. pneumoniae was 17%.
      Seventeen serotypes were detected amongst 55 strains analysed: 6A, 23F, 19F, 13,
      6B, 14A, 20, 7C, 1, 15B, 35B, 19A, 11A, 34, 5, 3 and 23A. Susceptibility testing
      revealed that nearly all (98%) were resistant to cotrimoxazole, 9% were resistant
      to penicillin and 7% to cefotaxime. Resistance to chloramphenicol and
      erythromycin was 2% and 4%, respectively. All isolates were fully sensitive to
      tetracycline. High levels of cotrimoxazole resistance and some resistance to
      other antimicrobial agents commonly used in Thika District Hospital shows that
      there is need to revise antimicrobial policy in this region in the treatment of
      invasive pneumococcal infections. The frequent serotypes found in this study have
      previously been associated with pneumococcal infections in children. Several of
      these serotypes are included in the ten-valent vaccine and therefore use of this
      vaccine will help reduce pneumococcal infections in Thika.

PMID- 29043161
TI  - Navigating laboratory services quality in challenging environments: A perspective
      for implementation in small, low-income countries and post-conflict settings.
AB  - The need to establish and maintain good laboratory practices is recognised
      universally. However, due to differences in resources available for health
      services in different countries, allocation of financial and human resources in
      poor countries is severely constrained. The constraints faced by poor countries
      call for innovative approaches that would guarantee the minimum acceptable
      quality while striving to meet the highest standards. In resource-limited
      setting, it may be justifiable to develop and use 'fit for purpose' quality
      standards based on internationally-recognised laboratory quality management
      frameworks or protocols.

PMID- 29043162
TI  - Biomedical laboratory science education: standardising teaching content in
      resource-limited countries.
AB  - BACKGROUND: There is a worldwide shortage of qualified laboratory personnel to
      provide adequate testing for the detection and monitoring of diseases. In an
      effort to increase laboratory capacity in developing countries, new skills have
      been introduced into laboratory services. Curriculum revision with a focus on
      good laboratory practice is an important aspect of supplying entry-level
      graduates with the competencies needed to meet the current needs. OBJECTIVES:
      Gaps in application and problem-solving competencies of newly graduated
      laboratory personnel were discovered in Ethiopia, Tanzania and Kenya. New medical
      laboratory teaching content was developed in Ethiopia, Tanzania and Kenya using
      national instructors, tutors, and experts and consulting medical laboratory
      educators from the United States of America (USA). METHOD: Workshops were held in
      Ethiopia to create standardised biomedical laboratory science (BMLS) lessons
      based on recently-revised course objectives with an emphasis on application of
      skills. In Tanzania, course-module teaching guides with objectives were developed
      based on established competency outcomes and tasks. In Kenya, example interactive
      presentations and lesson plans were developed by the USA medical laboratory
      educators prior to the workshop to serve as resources and templates for the
      development of lessons within the country itself. RESULTS: The new teaching
      materials were implemented and faculty, students and other stakeholders reported
      successful outcomes. CONCLUSIONS: These approaches to updating curricula may be
      helpful as biomedical laboratory schools in other countries address gaps in the
      competencies of entry-level graduates.

PMID- 29043163
TI  - Aetiology and factors associated with bacterial diarrhoeal diseases amongst urban
      refugee children in Eastleigh, Kenya: A case control study.
AB  - INTRODUCTION: Kenya is home to over 400 000 refugees from neighbouring countries.
      There is scanty information about diarrhoea amongst urban refugees in Kenya.
      OBJECTIVES: We investigated the enteric bacteria causing diarrhoea amongst urban
      refugee children and described the associated factors. METHOD: During the period
      of August-December 2010, urban refugee children between the ages of two and five
      who attended Eastleigh County Council Health Centre were enrolled into the study.
      Diarrhoeal cases were compared with age-matched children with no diarrhoea
      (controls). Stool specimens were collected and enteric bacteria isolated. A
      questionnaire was administered to identify risk factors. RESULTS: A total of 41
      cases and 41 controls were enrolled in the study. The age and country of origin
      were similar for cases and controls. The bacterial isolation rates amongst the
      cases were: non-pathogenic Escherichia coli 71%, Shigella dysenteriae 2.4%,
      Shigella flexneri 2.4%, Salmonella paratyphi 5%. For the controls, non-pathogenic
      E. coli 90% and enterotoxigenic E. coli (ETEC) 2.4% were amongst the organisms
      isolated. All isolates were resistant to amoxicillin; resistance to other
      antibiotics varied by isolate type. Factors associated independently with
      diarrhoea included children not washing their hands with soap (aOR 5.9, p <
      0.05), neighbour(s) having diarrhoea (aOR 39.8, p < 0.05), children not
      exclusively breastfed for their first 6 months (aOR 7.6, p < 0.05) and children
      eating food cooked the previous day (aOR 23.8, p = 0.002). CONCLUSIONS: Shigella
      species, Salmonella species and ETEC were found to be responsible for diarrhoea
      amongst the urban refugee children. Measures to control and guide the use of
      antibiotics are critical for the prevention of antibiotic resistance. Efforts to
      improve personal and domestic hygiene, including educational campaigns to promote
      appropriate handwashing, should be encouraged.

PMID- 29043164
TI  - The viral aetiology of influenza-like illnesses in Kampala and Entebbe, Uganda,
      2008.
AB  - BACKGROUND: As the threat of zoonoses and the emergence of pandemic-prone
      respiratory viruses increases, there is a need to establish baseline information
      on the incidence of endemic pathogens in countries worldwide. OBJECTIVES: To
      investigate the presence of viruses associated with influenza-like illnesses
      (ILI) in Uganda. METHODS: A cross-sectional study was conducted in which
      nasopharyngeal swab specimens were collected from patients diagnosed with ILI in
      Kampala and Entebbe between 14 August 2008 - 15 December 2008. A multiplex
      polymerase chain reaction assay for detecting 12 respiratory viruses was used.
      RESULTS: A total of 369 patients (52.3% females) was enrolled; the median age was
      6 years (range 1-70). One or more respiratory viruses were detected in 172
      (46.6%) cases and their prevalence were influenza A virus (19.2%), adenovirus
      (8.7%), human rhinovirus A (7.9%), coronavirus OC43 (4.3%), parainfluenza virus 1
      (2.7%), parainfluenza virus 3 (2.7%), influenza B virus (2.2%), respiratory
      syncytial virus B (2.2%), human metapneumovirus (1.4%), respiratory syncytial
      virus A (1.1%), parainfluenza virus 2 (0.5%) and coronavirus 229E (0.5%). There
      were 24 (14.0%) mixed infections. CONCLUSIONS: This study identified some of the
      respiratory viruses associated with ILI in Uganda. The circulation of some of the
      viruses was previously unknown in the study population. These results are useful
      in order to guide future surveillance and case management strategies involving
      respiratory illnesses in Uganda.

PMID- 29043165
TI  - Prevalence, intensity and complications of Microsporidium spores amongst HIV
      positive hospital patients in Ilorin, Nigeria.
AB  - BACKGROUND: Microsporidiasis, which is of great concern for immunocompromised
      patients, is poorly studied in developing countries. OBJECTIVES: A study was
      carried out amongst HIV-positive hospital patients and HIV-negative hospital
      controls in Ilorin, Nigeria, between January 2009 and July 2010 to determine the
      prevalence and intensity of Microsporidium spores and the complications
      associated with their presence. METHOD: Stool samples from 750 HIV-positive
      patients and 375 HIV-negative patients were studied using the Chromotrope-2R
      staining technique. Determination of CD4+ count was performed on the Partec
      Cyflow SL-3 CD4/8 instrument. Intensity of spores was determined by counting the
      total number of the spores in a 10 ul stained smear of stool. Images were
      captured with Phenix Microimage Analysis Software and data obtained were analysed
      using the Statistical Package for the Social Sciences. RESULTS: The prevalence of
      Microsporidium isolates amongst the HIV-positive hospital patients was
      significantly higher (42.4%) than amongst the HIV-negative controls (19.2%) (p <
      0.05). The intensity of microsporidial spores amongst HIV-positive hospital
      patients was also significantly higher than amongst the controls (p < 0.05).
      However, the difference in the intensity of spores amongst HIV-positive patients
      who were on antiretroviral therapy (n = 411) and those who were not (n = 339) was
      not significant (p = 0.236). Microsporidiasis in HIV infection infection was
      common amongst patients with with low CD4+ counts, diarrhoea, body rashes and
      cough. CONCLUSION: Both the prevalence and intensity of Microsporidiasis are high
      amongst HIV-positive hospital patients; campaigns to promote awareness,
      prevention and control are required. Laboratory testing for microsporidia in HIV
      patients should be performed routinely so as to identify the organism for prompt
      medical attention.

PMID- 29043166
TI  - Comparison of the COBAS/Ampliprep Taqman and Amplicor HIV-1 monitor tests in
      Lagos, Nigeria.
AB  - BACKGROUND: The use of real-time Polymerase chain reaction (PCR) technology
      options is increasing in resource-limited settings because they are faster,
      improve assay sensitivity, have higher throughput, larger dynamic ranges and
      reduced rates of contamination. In 2010, UNAIDS ranked Nigeria as the second
      highest population of people living with HIV and AIDS (2.98 million people) in
      the world. OBJECTIVE: The objective of this study was to compare the analytical
      performances of the Amplicor HIV-1 Monitor (version 1.5) and the COBAS
      Ampliprep/Taqman (version 2.0) used in monitoring HIV disease progression in HIV
      infected individuals. METHOD: In a cross-sectional study, HIV-1 RNA values
      obtained with the Amplicor HIV-1 monitor version 1.5 were compared with those of
      the COBAS/Ampliprep TaqMan HIV-1 version 2.0 in a routine clinical setting.
      Between May and November 2011, 176 plasma samples collected were analysed in
      parallel using both techniques. Data analysis was done using statgraphics
      Centurion XVI and Medcalc version 12.0. RESULT: The correlation coefficient for
      the two assays was 0.83 and the level of agreement using a Bland-Altman plot was
      94.2%. CONCLUSION: These findings suggest that the results from the two methods
      were comparable, hence the COBAS/Ampliprep Taqman version 2.0 is recommended for
      high-volume laboratories.

PMID- 29043168
TI  - Setting up a structured laboratory mentoring programme.
AB  - INTRODUCTION: Laboratory mentoring programmes can be an important vehicle to
      establish and solidify quality management systems and help laboratories achieve
      accreditation goals. Different mentoring approaches have been used with varying
      levels of success. The authors provide a guide to implementing a structured
      laboratory mentorship programme based on their practical field experience.
      METHOD: The study is based on experience in Lesotho as well as subsequent roll
      out of a similar approach in the other African countries of Zimbabwe, Mozambique,
      Swaziland and Cameroon between 2009 and 2011. SUMMARY: We highlight critical
      elements to consider when setting up a long-term, sustainable and well-structured
      mentorship programme. These elements include: well-defined goals; sufficient
      length of mentor engagement on site; standardised approach across laboratories;
      measurement of progress using standardised tools; well-structured reporting
      mechanisms; alignment of the programme with overall Ministry of Health plans; and
      selection and training of the mentors. These elements will differ in application,
      depending on countries' needs and available resources. A structured approach
      allows for scalability, comparison across laboratories and countries and an
      easier approach to budgeting and planning for countries intending to set up
      similar programmes.

PMID- 29043167
TI  - HIV and Tuberculosis co-infection impacts T-cell activation markers but not the
      numbers subset of regulatory T-cells in HIV-1 infected patients.
AB  - BACKGROUND: Tuberculosis (TB) has been shown to accelerate the clinical course of
      HIV infection, but the mechanisms by which this occurs are not well understood.
      Regulatory T-cells (Tregs) are known to dampen hyperactivation of the immune
      cells, but it remains unclear whether hyperactivation of T-cells in HIV infection
      is associated with a decrease of Tregs and what the effect Mycobacterium
      tuberculosis (MTB) co-infection has on T-cell activation and Tregs. OBJECTIVES:
      In this study, we aim to evaluate whether active TB is associated with the
      increased expression of T-cell activation markers and reduced number of Treg
      cells in HIV-1-infected patients. METHODS: This study was conducted on 69
      subjects consisting of 20 HIV-infected patients, 20 HIV and MTB co-infected
      patients, 19 MTB-infected patients and 10 uninfected control subjects negative
      for both MTB and HIV. The frequencies of T-cell activation markers (CD38 and HLA
      DR) and Treg cells (CD4+CD25+CD127-) were measured by flow cytometry. RESULTS:
      Significantly higher expression of CD38 and HLA-DR on CD4+ and CD8+ T-cells was
      found in MTB and HIV co-infected patients compared with HIV-infected patients.
      However, no significant difference in the percentage of Treg cells was reported
      between HIV patients with TB and those without. The study also showed a negative
      correlation between regulatory T-cells frequency and CD4+ T-cell counts.
      CONCLUSION: These results suggest that TB enhances the expression of peripheral T
      cell activation markers during HIV infection, whilst having no impact on the
      percentages of Treg cells.

PMID- 29043170
TI  - Haematopathology diagnosis: Role of multidisciplinary training workshops.

PMID- 29043169
TI  - In vitro antiplasmodial and cytotoxic properties of some medicinal plants from
      western Burkina Faso.
AB  - BACKGROUND: Resistance of malaria parasites to existing drugs complicates
      treatment, but an antimalarial vaccine that could protect against this disease is
      not yet available. It is therefore necessary to find new effective and affordable
      medicines. Medicinal plants could be a potential source of antimalarial agents.
      Some medicinal plants from Burkina Faso were evaluated for their antiplasmodial
      and cytotoxic properties in vitro. METHODS: Crude dichloromethane, methanol,
      water-methanol, aqueous and alkaloids extracts were prepared for 12 parts of 10
      plants. Chloroquine-resistant malaria strain K1 was used for the in vitro
      sensibility assay. The Plasmodium lactacte dehydrogenase technique was used to
      determine the 50% inhibitory concentration of parasites activity (IC50). The
      cytotoxic effects were determined with HepG2 cells, using the tetrazolium-based
      colorimetric technique, and the selectivity index (SI) was calculated. RESULTS:
      Sixty crude extracts were prepared. Seven extracts from Terminalia avicenoides
      showed IC50 < 5 ug/mL. The IC50 of dichloromethane, methanol, aqueous and
      alkaloids extracts ranged between 1.6 ug/mL and 4.5 ug/mL. Three crude extracts
      from Combretum collinum and three from Ficus capraefolia had an IC50 ranging
      between 0.2 ug/mL and 2.5 ug/mL. Crude extracts from these three plants had no
      cytotoxic effect, with SI > 1. The other plants have mostly moderate or no
      antimalarial effects. Some extracts from Cordia myxa, Ficus capraefolia and
      Opilia celtidifolia showed cytotoxicity, with an SI ranging between 0.4 and 0.9.
      CONCLUSION: Our study showed a good antiplasmodial in vitro activity of
      Terminalia avicenoides, Combretum collinum and Ficus capraefolia. These three
      plants may contain antiplasmodial molecules that could be isolated by bio-guided
      phytochemical studies.

PMID- 29043171
TI  - Virulence factors in environmental and clinical Vibrio cholerae from endemic
      areas in Kenya.
AB  - BACKGROUND: Since 1971, Kenya has had repeated cholera outbreaks. However, the
      cause of seasonal epidemics of cholera is not fully understood and neither are
      the factors that drive epidemics, both in Kenya and globally. OBJECTIVES: The
      objectives of the study were to determine the environmental reservoirs of V.
      cholerae during an interepidemic period in Kenya and to characterise their
      virulence factors. METHODS: One hundred (50 clinical, 50 environmental) samples
      were tested for V. cholerae isolates using both simplex and multiplex polymerase
      chain reaction. RESULTS: Both sediments and algae from fishing and landing bays
      yielded isolates of V. cholerae. Clinical strains were characterised along with
      the environmental strains for comparison. All clinical strains harboured ctxA,
      tcpA (El Tor), ompU, zot, ace, toxR, hylA (El Tor) and tcpI genes. Prevalence for
      virulence genes in environmental strains was hylA (El Tor) (10%), toxR (24%), zot
      (22%), ctxA (12%), tcpI (8%), hylA (26%) and tcpA (12%). CONCLUSION: The study
      sites, including landing bays and beaches, contained environmental V. cholerae,
      suggesting that these may be reservoirs for frequent epidemics. Improved hygiene
      and fish-handling techniques will be important in reducing the persistence of
      reservoirs.

PMID- 29043172
TI  - Candidaemia in a tertiary hospital in Nigeria.
AB  - BACKGROUND: Candidaemia is a widely-studied and reviewed topic in the developed
      world; however, there is a dearth of information on nosocomial candidaemia in
      Nigeria, despite the increasing use of more invasive therapeutic modalities,
      immunosuppressive agents and increasing incidence of immunosuppression as a
      result of malignancies and HIV. OBJECTIVES: To determine the hospital-based
      frequency of candidaemia in a tertiary hospital in Ibadan, Nigeria. METHOD: This
      was a prospective descriptive study which included 230 immunosuppressed patients.
      All isolates were identified to the species level using both conventional and
      automated methods. Thereafter, all Candida species isolated were tested for
      antifungal susceptibility using the broth microdilution method. RESULTS:
      Candidaemia occurred in 12 (5.21%) of the 230 study patients, with C. tropicalis
      accounting for 50% of the infections. Four patients (33.3%) presented with C.
      parapsilosis, one (8.3%) with C. albicans and one (8.3%) with a mixed infection
      of C. albicans and C. tropicalis. All 12 isolates were sensitive to fluconazole
      (minimal inhibitory concentration < 8 mg/mL). Univariate analysis revealed that
      old age, multiple surgeries and long-term hospitalisation were significant
      contributing factors for the occurrence of candidaemia. Eleven (91.7%) of the 12
      patients with candidaemia had Candida colonisation of other sterile sites
      including the bladder, peritoneum and trachea. Furthermore, bivariate analysis
      revealed that mucositis (p = 0.019) and diarrhoea (p = 0.017) were significantly
      associated with an increased risk of candidaemia. The crude mortality rate of
      candidaemia was 91.7%. CONCLUSION: This study highlights the significance of
      nosocomial candidaemia and the need for proactive laboratory investigation and
      clinical management of this life-threatening disease.

PMID- 29043173
TI  - An audit of immunofixation requesting practices at a South African referral
      laboratory.
AB  - BACKGROUND: It is common practice in most chemical pathology laboratories for
      reflective immunofixation electrophoresis (IFE) to occur following the detection
      or suspicion of a paraprotein on serum protein electrophoresis (SPEP). The
      chemical pathology laboratory at Inkosi Albert Luthuli Central Hospital (IALCH)
      in Durban, South Africa, is currently the only non-private laboratory in the
      KwaZulu Natal province that performs SPEP analysis, with current practice
      requiring that the clinician request IFE following suggestion by the laboratory
      after a suspicious SPEP result. OBJECTIVES: To review the current process for IFE
      at IALCH in the context of reflective testing and to examine the use of the alpha
      2-globulin/alpha-1-globulin ratio as a predictor of a positive IFE result.
      METHODS: Data for 1260 consecutive SPEP tests performed at the IALCH National
      Health Laboratory Service were collected between February and July 2011. SPEP and
      IFE were performed with a Sebia Hydrasys automated electrophoresis system. The
      alpha-2-globulin/alpha-1-globulin ratio was calculated using density of
      corresponding fractions on SPEP. RESULTS: Analysis revealed that of the 1260
      SPEPs performed during the analysis period, 304 IFEs were suggested by the
      reviewing pathologist. A total of 45 (15%) of the suggested IFEs were
      subsequently requested by the attending clinicians. Almost half (46.5%) (n = 20)
      of the suggested IFEs that were performed revealed the presence of a paraprotein.
      There was no statistically-significant difference between the alpha-2
      globulin/alpha-1-globulin ratio for patients with positive or negative IFEs (p
      value = 0.2). CONCLUSIONS: This study reveals the need for reflective addition of
      IFE testing by the laboratory following suspicious findings on SPEP.

PMID- 29043174
TI  - Development of a safer laboratory vervet monkey model for the study of human
      African trypanosomiasis.
AB  - BACKGROUND: There are three subspecies of Trypanosoma brucei: T. b. gambiense, T.
      b. rhodesiense and T. b. brucei. The first two are infectious to humans, whilst
      T. b. brucei is not. Identifying an animal model of T. b. brucei that mimics
      human African trypanosomiasis (HAT) would enable researchers to study HAT without
      subjecting themselves to undue risks such as accidental infection. OBJECTIVES:
      This study assessed the sequential clinical, parasitological and haematological
      changes in vervet monkeys infected with T. b. brucei. METHODS: Three vervet
      monkeys were infected with a 104 inoculum of T. b. brucei (isolate GUTat 1). Late
      stage disease was induced by subcurative treatment with diminazene aceturate 28
      days post-infection. The animals were treated curatively with melarsoprol upon
      relapse. Parasitaemia and clinical signs were monitored daily and, at weekly
      intervals, the monkeys' blood and cerebrospinal fluid (CSF) were sampled for
      haematology and parasitosis assessments, respectively. RESULTS: The first-peak
      parasitaemia was observed between seven and nine days post-infection. Clinical
      signs associated with the disease included fever, dullness, pallor of mucous
      membranes, lymphadenopathy, splenomegaly and oedema. Late-stage signs included
      stiffness of joints and lethargy. The monkeys developed a disease associated with
      microcytic hypochromic anaemia. There was an initial decline, followed by an
      increase, in total white blood cell counts from early- to late-stage disease.
      Trypanosomes were detected in the CSF and there was a significant increase in
      white cell counts in the CSF during late-stage disease. Infected vervet monkeys
      displayed classical clinical symptoms, parasitological and haematological trends
      that were similar to monkeys infected with T.b. rhodesiense. CONCLUSION: The T.
      b. brucei vervet monkey model can be used for studying HAT without putting
      laboratory technicians and researchers at high risk of accidental infection.

PMID- 29043175
TI  - Optimising the laboratory supply chain: The key to effective laboratory services.
AB  - BACKGROUND: The Supply Chain Management System (SCMS) is a contract managed under
      the Partnership for Supply Chain Management (PFSCM) consortium by the United
      States Agency for International Development (USAID). SCMS procures commodities
      for programmes supported by the US President's Emergency Plan for AIDS Relief
      (PEPFAR). From 2005 to mid-2012, PEPFAR, through SCMS, spent approximately $384
      million on non-pharmaceutical commodities. Of this, an estimated $90m was used to
      purchase flow cytometry technology, largely for flow cytometry platforms and
      reagents. OBJECTIVES: The purpose of this paper is to highlight the cost
      differences between low, medium and high utilisation rates of common CD4 testing
      instruments that have been procured though PEPFAR funding. METHOD: A scale of
      costs per test as a function of test volume through the machine was calculated
      for the two most common CD4 testing machines used in HIV programmes: Becton
      Dickinson (BD) FACSCountTM and BD FACSCaliburTM. Instrument utilisation data
      collected at the facility level in three selected countries were then used to
      calculate the onsite cost-per-test experienced in each country. RESULTS: Cost
      analyses indicated that a target of at least 40% utilisation for FACSCountTM and
      15% utilisation for FACSCaliburTM, respectively, closely approach maximal per
      test cost efficiency. The average utilisation rate for CD4 testing instruments
      varies widely by country, level of laboratory and partner (0% - 68%). CONCLUSION:
      Our analysis indicates that, because cost-per-test is related inversely to sample
      throughput, the underutilisation of flow cytometry machines is resulting in an
      increase in average cost-per-test for many instruments.

PMID- 29043176
TI  - Proficiency testing for HIV, tuberculosis and malaria diagnosis in clinical
      laboratories in Nigeria.
AB  - BACKGROUND: Proficiency testing (PT) is a means of verifying the reliability of
      laboratory results, but such programmes are not readily available to laboratories
      in developing countries. This project provided PT to laboratories in Nigeria.
      OBJECTIVES: To assess the proficiency of laboratories in the diagnosis of HIV,
      tuberculosis and malaria. METHODS: This was a prospective study carried out
      between 2009 and 2011. A structured questionnaire was administered to 106
      randomly-selected laboratories. Forty-four indicated their interest in
      participation and were enrolled. Four rounds of pre-characterised plasma panels
      for HIV, sputum films for tuberculosis and blood films for malaria were
      distributed quarterly by courier over the course of one year. The results were
      returned within two weeks and scores of >= 80% were reported as satisfactory.
      Mentoring was offered after the first and second PT rounds. RESULTS: Average HIV
      PT scores increased from 74% to 95% from the first round to the third round, but
      decreased in the fourth round. For diagnosis of tuberculosis, average scores
      increased from 42% in the first round to 78% in the second round; but a decrease
      to 34% was observed in the fourth round. Malaria PT performance was 2% at first,
      but average scores increased between the second and fourth rounds, culminating in
      a fourth-round score of 39%. Many participants requested training and mentoring.
      CONCLUSIONS: There were gross deficiencies in the quality of laboratory services
      rendered across Nigeria. In-country PT programmes, implemented in conjunction
      with mentoring, will improve coverage and diagnosis of HIV, tuberculosis and
      malaria.

PMID- 29043177
TI  - Improving access to new diagnostics through harmonised regulation: priorities for
      action.
AB  - A new generation of diagnostic tests is being developed for use at the point of
      care that could save lives and reduce the spread of infectious diseases through
      early detection and treatment. It is important that patients in developing
      countries have access to these products at affordable prices and without delay.
      Regulation of medical products is intended to ensure safety and quality whilst
      balancing the need for timely access to beneficial new products. Current
      regulatory oversight of diagnostic tests in developing countries is highly
      variable and weak regulation allows poor-quality tests to enter the market.
      However, inefficient or overzealous regulation results in unnecessary delays,
      increases costs and acts as a barrier to innovation and market entry. Setting
      international standards and streamlining the regulatory process could reduce
      these barriers. Four priority activities have been identified where convergence
      of standards and protocols or joint review of data would be advantageous: (1)
      adoption of a common registration file for pre-market approval; (2) convergence
      of quality standards for manufacturing site inspections; (3) use of common
      evaluation protocols, as well as joint review of data, to reduce unnecessary
      duplication of lengthy and costly clinical performance studies; and (4) use of
      networks of laboratories for post-market surveillance in order to monitor ongoing
      quality of diagnostic devices. The adoption and implementation of such measures
      in developing countries could accelerate access to new diagnostic tests that are
      safe and affordable.

PMID- 29043178
TI  - The interface between clinicians and laboratory staff: A field study in northern
      Tanzania.
AB  - BACKGROUND: Strengthening the communication and professional relationships
      between clinicians and laboratory workers is essential in order to positively
      change clinicians' attitudes about the reliability of diagnostic tests, enhancing
      the use of laboratory diagnostics and, ultimately, improving patient care. We
      developed an analytical framework to gain insight into the factors that influence
      communication amongst health professionals. OBJECTIVE: To explore whether the
      interaction between clinicians and laboratory workers influences the use of
      laboratory test results in clinical decision making. METHODS: Four health
      facilities in northern Tanzania were selected using convenience sampling, whereas
      study participants were selected using purposive sampling. The quantitative and
      qualitative data collection methods included self-administered questionnaires;
      semi-structured, individual interviews; in-depth, individual interviews; and/or
      focus group discussions with clinicians and laboratory workers. Thematic content
      analyses were performed on qualitative data based on the framework. Descriptive
      statistical analyses of quantitative data were conducted using Microsoft Excel.
      RESULTS: Contact between clinicians and laboratory professionals is seldom
      institutionalised and collaboration is rare. The clinicians believe collaboration
      with laboratory staff is a challenge because of the gap in education levels.
      Laboratory workers' education levels are often lower than their positions
      require, leading to clinicians' lack of respect for and confidence in laboratory
      professionals, which compromises the laboratory staff's motivation. CONCLUSIONS:
      Hospital managers, clinicians and laboratory workers need to recognise the
      critical and complementary roles each professional plays and the importance of
      addressing the gap between them. Field application of the framework proved
      successful, justifying the expansion of this study to a larger geographical area
      to include additional healthcare institutions.

PMID- 29043179
TI  - Understanding the interface between clinical and laboratory staff.
AB  - BACKGROUND: The interface between clinicians and laboratory staff is where the
      two meet and work together to provide quality care to their clients (patients).
      Effectiveness of the interface depends on the way the two groups of professionals
      relate to and communicate with each other. The number and type of tests requested
      and the use of the test results for clinical decision making can be influenced by
      the interface between clinicians and laboratory staff. A model to understand the
      factors and dynamics around the interface is lacking. OBJECTIVES: To propose a
      new conceptual model to gain insight and analyse factors that influence the
      laboratory-clinical staff interface. METHODS: To develop the conceptual model, a
      literature study was performed, regulatory guidelines and standards for
      laboratories were analysed and discussions were held with experts on the topic.
      RESULT: A conceptual model and analytical framework provided good guidance in
      understanding and assessing the organisational and personal factors shaping the
      interface. The model was based on three elements: (1) the three phases of
      communication (pre-analytical, analytical and post-analytical); (2) the
      organisational and personal factors of interaction; and (3) the socio-political,
      economic and cultural context in which clinicians and laboratory staff operate.
      CONCLUSION: Assessment of the interface between clinicians and laboratory workers
      can be performed in a systematic way. Applying this model will provide
      information to managers of health institutions and heads of laboratories and
      clinical departments about what happens when clinicians and laboratory staff
      interact, thus aiding them in designing strategies to improve this interface.

PMID- 29043180
TI  - Tuberculosis alters pancreatic enzymes in the absence of pancreatitis.
AB  - BACKGROUND: Lipases and phospholipases are thought to contribute to the
      pathogenesis of Mycobacterium tuberculosis (MTB) infection. Genes coding for
      lipases, phospholipases and amylase are present in MTB, enabling the bacteria to
      produce these enzymes. OBJECTIVE: To compare serum lipase and amylase activity
      levels in patients with tuberculosis (TB) against those of healthy controls.
      METHODS: Serum lipase and amylase activity levels were measured in 99 patients
      and 143 healthy controls using the Vitros 250 Chemistry analyser. Reference
      ranges for serum lipase and amylase were 23-300 U/L and 30-110 U/L, respectively.
      RESULTS: Lipase was higher in patients with MTB than in controls (81.5 IU/L
      versus 66.5 IU/L, p = 0.006). Similarly, amylase was higher in the MTB patient
      group (76 IU/L versus 60 IU/L, p < 0.001). The Pearson correlation coefficient
      for lipase versus amylase (R) was higher in the controls (R = 0.351, p < 0.0001)
      compared with MTB patients (R = 0.217, p = 0.035). Amongst MTB patients, lipase
      activity correlated positively with erythrocyte sedimentation rate (ESR) (R =
      0.263, p = 0.013), but not with haemoglobin concentration or treatment duration.
      A weak inverse correlation was noted between ESR and treatment duration (R = 
      0.222, p = 0.028). CONCLUSION: Pancreatic enzyme levels differ between MTB
      patients and normal controls; however, this difference still lies within the
      normal range. The concomitant increase of lipase with ESR, an inflammatory
      marker, could conceivably suggest a causal relationship. Further research is
      necessary to characterise MTB-derived enzymes for diagnostic and therapeutic
      utility.

PMID- 29043181
TI  - Phlebotomy and quality in the African laboratory.
AB  - Phlebotomy, the act of drawing blood through venepuncture, is one of the most
      common medical procedures in healthcare, as well as being a basis for diagnosis
      and treatment. A review of the available research has highlighted the dearth of
      information on the phlebotomy practice in Africa. Several studies elsewhere have
      shown that the pre-analytical phase (patient preparation, specimen collection and
      identification, transportation, preparation for analysis and storage) is the most
      error-prone process in laboratory medicine. The validity of any laboratory test
      result hinges on specimen quality; thus, as the push for laboratory quality
      improvement in Africa gathers momentum, the practice of phlebotomy should be
      subjected to critical appraisal. This article offers several suggestions for the
      improvement of phlebotomy in Africa.

PMID- 29043182
TI  - View from the top: Involvement of Namibia's health ministry in laboratory quality
      improvement.

PMID- 29043183
TI  - Improving quality in national reference laboratories: The role of SLMTA and
      mentorship.
AB  - BACKGROUND: The Nigerian Institute of Medical Research houses two reference
      laboratories: the virology and tuberculosis laboratories. Both were enrolled in
      the Strengthening Laboratory Management Toward Accreditation (SLMTA) programme.
      OBJECTIVE: To describe the impact of SLMTA and discuss factors affecting the
      results, with an emphasis on mentorship. METHODS: The SLMTA programme was
      implemented from April 2010 through November 2012. Participants attended three
      workshops and executed quality improvement projects; laboratory auditors
      evaluated performance using a standard checklist. The virology laboratory did not
      receive mentorship; however, the tuberculosis laboratory had an international
      mentor who visited the laboratory four times during the programme, spending two
      to four weeks embedded within the laboratory during each visit. RESULTS: There
      was an overall improvement in the performance of both laboratories, with the
      virology laboratory increasing 13% (from 80% at baseline to 93% at exit audit)
      and the tuberculosis laboratory increasing 29% (from 66% to 95%). These scores
      were maintained nine months later at the surveillance audit. CONCLUSION: The
      SLMTA programme resulted in improved and sustained quality management performance
      for both laboratories. Mentoring was a possible factor in the substantial
      improvement made by the tuberculosis laboratory and should be considered in order
      to augment the training received from the SLMTA workshops.

PMID- 29043184
TI  - Creating a sustainable culture of quality through the SLMTA programme in a
      district hospital laboratory in Kenya.
AB  - BACKGROUND: Bungoma District Hospital Laboratory (BDHL), which supports a 200-bed
      referral facility, began its Strengthening Laboratory Management Toward
      Accreditation (SLMTA) journey in 2011 together with eight other laboratories in
      the second round of SLMTA rollout in Kenya. OBJECTIVES: To describe how the SLMTA
      programme and enhanced quality interventions changed the culture and management
      style at BDHL and instilled a quality system designed to sustain progress for
      years to come. METHODS: SLMTA implementation followed the standard three-workshop
      series, mentorship site visits and audits. In order to build sustainability of
      progress, BDHL integrated quality improvement processes into its daily
      operations. The lab undertook a process of changing its internal culture to align
      all hospital stakeholders - including upper management, clinicians, laboratory
      staff and maintenance staff - to the mission of sustainable quality practices at
      BDHL. RESULTS: After 16 months in the SLMTA programme, BDHL improved from zero
      stars (38%) to four stars (89%). Over a period of two to three years, external
      quality assessment results improved from 47% to 87%; staff punctuality increased
      from 49% to 82%; clinician complaints decreased from 83% to 16; rejection rates
      decreased from 12% to 3%; and annual equipment repairs decreased from 40 to 15.
      Twelve months later the laboratory scored three stars (81%) in an external
      surveillance audit conducted by Kenya Accreditation Service (KENAS). CONCLUSION:
      Management buy-in, staff participation, use of progress-monitoring tools and
      feedback systems, as well as incorporation of improvement processes into routine
      daily activities, were vital in developing and sustaining a culture of quality
      improvement.

PMID- 29043185
TI  - One laboratory's progress toward accreditation in Tanzania.
AB  - INTRODUCTION: The Amana Regional Hospital Laboratory in Tanzania was selected,
      along with 11 other regional and district laboratories, to participate in a pilot
      programme for laboratory quality improvement using the Strengthening Laboratory
      Management Toward Accreditation (SLMTA) training programme. PROGRAMME
      IMPLEMENTATION: The SLMTA programme entailed hands-on learning, improvement
      projects between and after a three-workshop series, supervisory visits from an
      oversight team and an expert laboratory mentor to facilitate and coach the
      process. Audits were conducted at baseline, exit (approximately one year after
      baseline) and follow-up (seven months after exit) using the Stepwise Laboratory
      Quality Improvement Process Towards Accreditation (SLIPTA) checklist. Quality
      stars (zero to five) were awarded based on audit scores. RESULTS: With a
      dedicated staff and strong leadership from laboratory management, Amana
      Laboratory implemented processes, policies and procedures recommended as elements
      of best laboratory practices. The laboratory improved from zero stars (36%) at
      baseline to successfully achieving three stars (81%) at exit. This was the
      highest score achieved by the 12 laboratories in the programme (the median exit
      score amongst the other laboratories was 58%). Seven months after completion of
      the programme, the laboratory regressed to one star (62%). DISCUSSION: As the
      SLMTA improvement programme progressed, Amana Laboratory's positive attitude and
      hard work prevailed. With the assistance of a mentor and the support of the
      facility's management a strong foundation of good practices was established.
      Although not all improvements were maintained after the conclusion of the
      programme and the laboratory dropped to a one-star rating, the laboratory
      remained at a higher level than most laboratories in the programme.

PMID- 29043186
TI  - From grass to grace: How SLMTA revolutionised the Bamenda Regional Hospital
      Laboratory in Cameroon.
AB  - BACKGROUND: Public health laboratories form the foundation on which today's
      clinical laboratory practice in Cameroon is built. The advent of the
      Strengthening Laboratory Management Toward Accreditation (SLMTA) programme in
      2009 empowered the Bamenda Regional Hospital Laboratory (BRHL) to improve its
      working culture, practices and management. OBJECTIVES: To evaluate the results of
      SLMTA implementation at BRHL and discuss lessons learned. METHOD: In 2010, the
      SLMTA programme was rolled out in Cameroon to improve laboratory quality
      management systems in five laboratories, including BRHL. Three workshops were
      conducted (the first centralised, the remaining two on-site at each laboratory)
      and improvement projects were implemented after each workshop with the assistance
      of mentors. Audits were used in order to evaluate performance and to identify
      areas for further improvement. RESULTS: BRHL had the lowest score (18%) amongst
      the cohort at the baseline audit and the highest (81%) at the official Stepwise
      Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) audit
      conducted in August 2013 by the African Society for Laboratory Medicine.
      Improvements were observed in each of the 12 Quality System Essentials;
      improvement was especially noteworthy in the areas of facilities and safety, and
      purchasing and inventory. Staff investment and pride in the quality of laboratory
      services increased. CONCLUSION: BRHL's remarkable improvement was achieved with a
      combination of SLMTA training activities, intensive on-site mentorship and the
      collective focus of all laboratory staff. The experience at Bamenda Hospital
      illustrates what can be achieved when a laboratory successfully harnesses the
      energy of its staff and implements changes to improve the quality of services in
      a transformation taking them from grass to grace.

PMID- 29043187
TI  - Accelerating the spread of laboratory quality improvement efforts in Botswana.
AB  - BACKGROUND: In 2002, the Ministry of Health (MoH) of Botswana began its journey
      toward laboratory accreditation in an effort to enhance the quality of laboratory
      services. After a difficult start, the MoH recognised the need for a more
      practical and sustainable method for change that could be implemented nationally;
      they therefore adopted the Strengthening Laboratory Management Toward
      Accreditation (SLMTA) programme. OBJECTIVE: This study describes the process and
      lessons learned in implementing SLMTA and the role of supplemental training and
      mentoring so as to achieve Botswana's national laboratory quality improvement
      goal. METHODS: Eight laboratories were enrolled into the SLMTA programme in 2010,
      which included a series of workshops and improvement projects conducted over nine
      months. Four of these laboratories received supplementary training and focused
      mentorship from the Botswana Bureau of Standards (BOBS). Laboratory performance
      was measured at baseline and exit using the World Health Organization Regional
      Office for Africa's Stepwise Laboratory Quality Improvement Process Towards
      Accreditation (SLIPTA) checklist. One laboratory did not receive an exit audit
      and was thus excluded from the analysis. RESULTS: An 18 percentage-point
      improvement was observed when comparing the median baseline score (53%) to the
      median exit score (71%) for the seven laboratories. Laboratories that received
      additional training and mentorship from BOBS improved 21 percentage points,
      whilst non-BOBS-mentored laboratories improved eight percentage points. Hospital
      management buy-in and strong laboratory staff camaraderie were found to be
      essential for the positive changes observed. CONCLUSION: SLMTA facilitated
      improvements in laboratory quality management systems, yielding immediate and
      measurable results. This study suggests that pairing the SLMTA programme with
      additional training and mentorship activities may lead to further increases in
      laboratory performance; and that SLMTA is a practical approach to extending
      quality improvement to MOH laboratories.

PMID- 29043188
TI  - Translating a National Laboratory Strategic Plan into action through SLMTA in a
      district hospital laboratory in Botswana.
AB  - BACKGROUND: The Ministry of Health (MOH) of Botswana adopted Strengthening
      Laboratory Management Toward Accreditation (SLMTA), a structured quality
      improvement programme, as a key tool for the implementation of quality management
      systems in its public health laboratories. Coupled with focused mentorship, this
      programme aimed to help MOH achieve the goals of the National Laboratory
      Strategic Plan to provide quality and timely clinical diagnoses. OBJECTIVES: This
      article describes the impact of implementing SLMTA in Sekgoma Memorial Hospital
      Laboratory (SMHL) in Serowe, Botswana. METHODS: SLMTA implementation in SMHL
      included trainings, improvement projects, site visits and focused mentorship. To
      measure progress, audits using the Stepwise Laboratory Quality Improvement
      Process Towards Accreditation (SLIPTA) checklist were conducted at baseline and
      exit of the programme, with scores corresponding to a zero- to five-star scale.
      Turnaround times, customer satisfaction, and several other health service
      indicators were tracked. RESULTS: The laboratory scored 53% (zero stars) at the
      baseline audit and 80% (three stars) at exit. Nearly three years later, the
      laboratory scored 85% (four stars) in an official audit conducted by the African
      Society for Laboratory Medicine. Turnaround times became shorter after SLMTA
      implementation, with reductions ranging 19% to 52%; overall patient satisfaction
      increased from 56% to 73%; and clinician satisfaction increased from 41% to 72%.
      Improvements in inventory management led to decreases in discarded reagents,
      reducing losses from US $18 000 in 2011 to $40 in 2013. CONCLUSION: The SLMTA
      programme contributed to enhanced performance of the laboratory, which in turn
      yielded potential positive impacts for patient care at the hospital.

PMID- 29043189
TI  - Innovative strategies for a successful SLMTA country programme: The Rwanda story.
AB  - BACKGROUND: In 2009, to improve the performance of laboratories and strengthen
      healthcare systems, the World Health Organization Regional Office for Africa (WHO
      AFRO) and partners launched two initiatives: a laboratory quality improvement
      programme called Strengthening Laboratory Management Toward Accreditation
      (SLMTA), and what is now called the Stepwise Laboratory Quality Improvement
      Process Towards Accreditation (SLIPTA). OBJECTIVES: This study describes the
      achievements of Rwandan laboratories four years after the introduction of SLMTA
      in the country, using the SLIPTA scoring system to measure laboratory progress.
      METHODS: Three cohorts of five laboratories each were enrolled in the SLMTA
      programme in 2010, 2011 and 2013. The cohorts used SLMTA workshops, improvement
      projects, mentorship and quarterly performance-based financing incentives to
      accelerate laboratory quality improvement. Baseline, exit and follow-up audits
      were conducted over a two-year period from the time of enrolment. Audit scores
      were used to categorise laboratory quality on a scale of zero (< 55%) to five
      (95% - 100%) stars. RESULTS: At baseline, 14 of the 15 laboratories received zero
      stars with the remaining laboratory receiving a two-star rating. At exit, five
      laboratories received one star, six received two stars and four received three
      stars. At the follow-up audit conducted in the first two cohorts approximately
      one year after exit, one laboratory scored two stars, five laboratories earned
      three stars and four laboratories, including the National Reference Laboratory,
      achieved four stars. CONCLUSION: Rwandan laboratories enrolled in SLMTA showed
      improvement in quality management systems. Sustaining the gains and further
      expansion of the SLMTA programme to meet country targets will require continued
      programme strengthening.

PMID- 29043190
TI  - SLIPTA e-Tool improves laboratory audit process in Vietnam and Cambodia.
AB  - BACKGROUND: The Stepwise Laboratory Quality Improvement Process Towards
      Accreditation (SLIPTA) checklist is used worldwide to drive quality improvement
      in laboratories in developing countries and to assess the effectiveness of
      interventions such as the Strengthening Laboratory Management Toward
      Accreditation (SLMTA) programme. However, the paper-based format of the checklist
      makes administration cumbersome and limits timely analysis and communication of
      results. DEVELOPMENT OF E-TOOL: In early 2012, the SLMTA team in Vietnam
      developed an electronic SLIPTA checklist tool. The e-Tool was pilot tested in
      Vietnam in mid-2012 and revised. It was used during SLMTA implementation in
      Vietnam and Cambodia in 2012 and 2013 and further revised based on auditors'
      feedback about usability. OUTCOMES: The SLIPTA e-Tool enabled rapid turn-around
      of audit results, reduced workload and language barriers and facilitated analysis
      of national results. Benefits of the e-Tool will be magnified with in-country
      scale-up of laboratory quality improvement efforts and potential expansion to
      other countries.

PMID- 29043191
TI  - Using standard and institutional mentorship models to implement SLMTA in Kenya.
AB  - BACKGROUND: Kenya is home to several high-performing internationally-accredited
      research laboratories, whilst most public sector laboratories have historically
      lacked functioning quality management systems. In 2010, Kenya enrolled an initial
      eight regional and four national laboratories into the Strengthening Laboratory
      Management Toward Accreditation (SLMTA) programme. To address the challenge of a
      lack of mentors for the regional laboratories, three were paired, or 'twinned',
      with nearby accredited research laboratories to provide institutional mentorship,
      whilst the other five received standard mentorship. OBJECTIVES: This study
      examines results from the eight regional laboratories in the initial SLMTA group,
      with a focus on mentorship models. METHODS: Three SLMTA workshops were
      interspersed with three-month periods of improvement project implementation and
      mentorship. Progress was evaluated at baseline, mid-term, and exit using the
      Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA)
      audit checklist and scores were converted into a zero- to five-star scale.
      RESULTS: At baseline, the mean score for the eight laboratories was 32%; all
      laboratories were below the one-star level. At mid-term, all laboratories had
      measured improvements. However, the three twinned laboratories had increased an
      average of 32 percentage points and reached one to three stars; whilst the five
      non-twinned laboratories increased an average of 10 percentage points and
      remained at zero stars. At exit, twinned laboratories had increased an average 12
      additional percentage points (44 total), reaching two to four stars; non-twinned
      laboratories increased an average of 28 additional percentage points (38 total),
      reaching one to three stars. CONCLUSION: The partnership used by the twinning
      model holds promise for future collaborations between ministries of health and
      state-of-the-art research laboratories in their regions for laboratory quality
      improvement. Where they exist, such laboratories may be valuable resources to be
      used judiciously so as to accelerate sustainable quality improvement initiated
      through SLMTA.

PMID- 29043192
TI  - Driving hospital transformation with SLMTA in a regional hospital in Cameroon.
AB  - BACKGROUND: Inspired by the transformation of the Regional Hospital Buea
      laboratory through implementation of the Strengthening Laboratory Management
      Toward Accreditation (SLMTA) programme, hospital management adapted the SLMTA
      toolkit to drive hospital-wide quality improvement. OBJECTIVE: This paper
      describes changes in the hospital following the quality improvement activities in
      hygiene and sanitation, the outpatient waiting area and the surgical and
      maternity wards. METHODS: In March 2011, hospital management established a
      quality improvement task force and created a hospital-wide quality improvement
      roadmap, following the SLMTA model. The roadmap comprised improvement projects,
      accountability plans, patient feedback forms and log books to track quality
      indicators including patient wait time, satisfaction level, infection rates,
      birth outcomes and hospital revenue. RESULTS: There was steady improvement in
      service delivery during the 11 months after the introduction of the quality
      improvement initiatives: patient wait time at the reception was reduced from
      three hours to less than 30 minutes and patient satisfaction increased from 15%
      to 60%. Treatment protocols were developed and documented for various units,
      infrastructure and workflow processes were improved and there was increased staff
      awareness of the importance of providing quality services. Maternal infection
      rates dropped from 3% to 0.5% and stillbirths from 5% to < 1%. The number of
      patients increased as a result of improved services, leading to a 25% increase in
      hospital revenue. CONCLUSION: The SLMTA programme was adapted successfully to
      meet the needs of the entire hospital. Such a programme has the potential to
      impact positively on hospital quality systems; consideration should be made for
      development of a formal SLMTA-like programme for hospital quality improvement.

PMID- 29043193
TI  - Progressing beyond SLMTA: Are internal audits and corrective action the key
      drivers of quality improvement?
AB  - BACKGROUND: Kenya has implemented the Strengthening Laboratory Management Toward
      Accreditation (SLMTA) programme to facilitate quality improvement in medical
      laboratories and to support national accreditation goals. Continuous quality
      improvement after SLMTA completion is needed to ensure sustainability and
      continue progress toward accreditation. METHODS: Audits were conducted by
      qualified, independent auditors to assess the performance of five enrolled
      laboratories using the Stepwise Laboratory Quality Improvement Process Towards
      Accreditation (SLIPTA) checklist. End-of-programme (exit) and one year post
      programme (surveillance) audits were compared for overall score, star level (from
      zero to five, based on scores) and scores for each of the 12 Quality System
      Essential (QSE) areas that make up the SLIPTA checklist. RESULTS: All
      laboratories improved from exit to surveillance audit (median improvement 38
      percentage points, range 5-45 percentage points). Two laboratories improved from
      zero to one star, two improved from zero to three stars and one laboratory
      improved from three to four stars. The lowest median QSE scores at exit were:
      internal audit; corrective action; and occurrence management and process
      improvement (< 20%). Each of the 12 QSEs improved substantially at surveillance
      audit, with the greatest improvement in client management and customer service,
      internal audit and information management (>= 50 percentage points). The two
      laboratories with the greatest overall improvement focused heavily on the
      internal audit and corrective action QSEs. CONCLUSION: Whilst all laboratories
      improved from exit to surveillance audit, those that focused on the internal
      audit and corrective action QSEs improved substantially more than those that did
      not; internal audits and corrective actions may have acted as catalysts, leading
      to improvements in other QSEs. Systematic identification of core areas and best
      practices to address them is a critical step toward strengthening public medical
      laboratories.

PMID- 29043194
TI  - Decentralised facility-based training as an alternative model for SLMTA
      implementation: The Cameroon experience.
AB  - BACKGROUND: The Strengthening Laboratory Management Toward Accreditation (SLMTA)
      programme is designed to build institutional capacity to help strengthen the
      tiered laboratory system. Most countries implement the SLMTA three-workshop
      series using a centralised model, whereby participants from several laboratories
      travel to one location to be trained together. OBJECTIVES: We assessed the
      effectiveness and cost of conducting SLMTA training in a decentralised manner as
      compared to centralised training. METHODS: SLMTA was implemented in five pilot
      laboratories in Cameroon between October 2010 and October 2012 by means of a
      series of workshops, laboratory improvement projects and on-site mentorship. The
      first workshop was conducted in the traditional centralised approach. The second
      and third workshops were decentralised, delivered on-site at each of the five
      enrolled laboratories. Progress was monitored by repeated audits using the
      Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA)
      checklist. RESULTS: Audit scores for all laboratories improved steadily through
      the course of the programme. Median improvement was 11 percentage points after
      the first (centralised) training and an additional 24 percentage points after the
      second (decentralised) training. The estimated per-laboratory cost of the two
      training models was approximately the same at US$21 000. However, in the
      decentralised model approximately five times as many staff members were trained,
      although it also required five times the amount of trainer time. CONCLUSION:
      Decentralised SLMTA training was effective in improving laboratory quality and
      should be considered as an alternative to centralised training.

PMID- 29043195
TI  - Perceptions and attitudes toward SLMTA amongst laboratory and hospital
      professionals in Ethiopia.
AB  - BACKGROUND: Strengthening Laboratory Management Toward Accreditation (SLMTA) is a
      competency-based management training programme. Assessing health professionals'
      views of SLMTA provides feedback to inform program planning, implementation and
      evaluation of SLMTA's training, communication and mentorship components.
      OBJECTIVES: To assess laboratory professionals' and hospital chief executive
      officers' (CEOs) perceptions and attitudes toward the SLMTA programme in
      Ethiopia. METHODS: A cross-sectional descriptive survey was conducted in March
      2013 using a structured questionnaire to collect qualitative data from 72
      laboratory professionals and hospital CEOs from 17 health facilities,
      representing all regions and two city administrations in Ethiopia. Focus groups
      were conducted with laboratory professionals and hospital administration to gain
      insight into the strengths and challenges of the SLMTA programme so as to guide
      future planning and implementation. RESULTS: Ethiopian laboratory professionals
      at all levels had a supportive attitude toward the SLMTA programme. They believed
      that SLMTA substantially improved laboratory services and acted as a catalyst for
      total healthcare reform and improvement. They also noted that the SLMTA programme
      achieved marked progress in laboratory supply chain, sample referral, instrument
      maintenance and data management systems. In contrast, nearly half of the
      participating hospital CEOs, especially those associated with low-scoring
      laboratories, were sceptical about the SLMTA programme, believing that the
      benefits of SLMTA were outweighed by the level of human resources and time
      commitment required. They also voiced concerns about the cost and sustainability
      of SLMTA. CONCLUSION: This study highlights the need for stronger engagement and
      advocacy with hospital administration and the importance of addressing concerns
      about the cost and sustainability of the SLMTA programme.

PMID- 29043196
TI  - Maximising mentorship: Variations in laboratory mentorship models implemented in
      Zimbabwe.
AB  - BACKGROUND: Laboratory mentorship has proven to be an effective tool in building
      capacity and assisting laboratories in establishing quality management systems.
      The Zimbabwean Ministry of Health and Child Welfare implemented four mentorship
      models in 19 laboratories in conjunction with the Strengthening Laboratory
      Management Toward Accreditation (SLMTA) programme. OBJECTIVES: This study
      outlines how the different models were implemented, cost involved per model and
      results achieved. METHODS: Eleven of the laboratories had been trained previously
      in SLMTA (Cohort I). They were assigned to one of three mentorship models based
      on programmatic considerations: Laboratory Manager Mentorship (Model 1, four
      laboratories); One Week per Month Mentorship (Model 2, four laboratories); and
      Cyclical Embedded Mentorship (Model 3, three laboratories). The remaining eight
      laboratories (Cohort II) were enrolled in Cyclical Embedded Mentorship
      incorporated with SLMTA training (Model 4). Progress was evaluated using a
      standardised audit checklist. RESULTS: At SLMTA baseline, Model 1-3 laboratories
      had a median score of 30%. After SLMTA, at mentorship baseline, they had a median
      score of 54%. At the post-mentorship audit they reached a median score of 75%.
      Each of the three mentorship models for Cohort I had similar median improvements
      from pre- to post-mentorship (17 percentage points for Model 1, 23 for Model 2
      and 25 for Model 3; p > 0.10 for each comparison). The eight Model 4 laboratories
      had a median baseline score of 24%; after mentorship, their median score
      increased to 63%. Median improvements from pre-SLMTA to post-mentorship were
      similar for all four models. CONCLUSION: Several mentorship models can be
      considered by countries depending on the available resources for their
      accreditation implementation plan.

PMID- 29043197
TI  - Weighing the costs: Implementing the SLMTA programme in Zimbabwe using internal
      versus external facilitators.
AB  - BACKGROUND: In 2010, the Zimbabwe Ministry of Health and Child Welfare (MoHCW)
      adopted the Strengthening Laboratory Management Toward Accreditation (SLMTA)
      programme as a tool for laboratory quality systems strengthening. OBJECTIVES: To
      evaluate the financial costs of SLMTA implementation using two models (external
      facilitators; and internal local or MoHCW facilitators) from the perspective of
      the implementing partner and to estimate resources needed to scale up the
      programme nationally in all 10 provinces. METHODS: The average expenditure per
      laboratory was calculated based on accounting records; calculations included
      implementing partner expenses but excluded in-kind contributions and salaries of
      local facilitators and trainees. We also estimated theoretical financial costs,
      keeping all contextual variables constant across the two models. Resource needs
      for future national expansion were estimated based on a two-phase implementation
      plan, in which 12 laboratories in each of five provinces would implement SLMTA
      per phase; for the internal facilitator model, 20 facilitators would be trained
      at the beginning of each phase. RESULTS: The average expenditure to implement
      SLMTA in 11 laboratories using external facilitators was approximately US$5800
      per laboratory; expenditure in 19 laboratories using internal facilitators was
      approximately $6000 per laboratory. The theoretical financial cost of
      implementing a 12-laboratory SLMTA cohort keeping all contextual variables
      constant would be approximately $58 000 using external facilitators; or $15 000
      using internal facilitators, plus $86 000 to train 20 facilitators. The financial
      cost for subsequent SLMTA cohorts using the previously-trained internal
      facilitators would be approximately $15 000, yielding a break-even point of 2
      cohorts, at $116 000 for either model. Estimated resources required for national
      implementation in 120 laboratories would therefore be $580 000 using external
      facilitators ($58 000 per province) and $322 000 using internal facilitators ($86
      000 for facilitator training in each of two phases plus $15 000 for SLMTA
      implementation in each province). CONCLUSION: Investing in training of internal
      facilitators will result in substantial savings over the scale-up of the
      programme. Our study provides information to assist policy makers to develop
      strategic plans for investing in laboratory strengthening.

PMID- 29043198
TI  - Working toward a sustainable laboratory quality improvement programme through
      country ownership: Mozambique's SLMTA story.
AB  - BACKGROUND: Launched in 2009, the Strengthening Laboratory Management Toward
      Accreditation (SLMTA) programme has emerged as an innovative approach for the
      improvement of laboratory quality. In order to ensure sustainability, Mozambique
      embedded the SLMTA programme within the existing Ministry of Health (MOH)
      laboratory structure. OBJECTIVE: This article outlines the steps followed to
      establish a national framework for quality improvement and embedding the SLMTA
      programme within existing MOH laboratory systems. METHODS: The MOH adopted SLMTA
      as the national laboratory quality improvement strategy, hired a dedicated
      coordinator and established a national laboratory quality technical working group
      comprising mostly personnel from key MOH departments. The working group developed
      an implementation framework for advocacy, training, mentorship, supervision and
      audits. Emphasis was placed on building local capacity for programme activities.
      After receiving training, a team of 25 implementers (18 from the MOH and seven
      from partner organisations) conducted baseline audits (using the Stepwise
      Laboratory Quality Improvement Process Towards Accreditation [SLIPTA] checklist),
      workshops and site visits in six reference and two central hospital laboratories.
      Exit audits were conducted in six of the eight laboratories and their results are
      presented. RESULTS: The six laboratories demonstrated substantial improvement in
      audit scores; median scores increased from 35% at baseline to 57% at exit. It has
      been recommended that the National Tuberculosis Reference Laboratory apply for
      international accreditation. CONCLUSION: Successful implementation of SLMTA
      requires partnership between programme implementers, whilst effectiveness and
      long-term viability depend on country leadership, ownership and commitment.
      Integration of SLMTA into the existing MOH laboratory system will ensure
      durability beyond initial investments. The Mozambican model holds great promise
      that country leadership, ownership and institutionalisation can set the stage for
      programme success and sustainability.

PMID- 29043199
TI  - Making great strides in medical laboratory quality.

PMID- 29043200
TI  - A comprehensive review of the SLMTA literature part 1: Content analysis and
      future priorities.
AB  - BACKGROUND: Since its introduction in 2009, the Strengthening Laboratory
      Management Toward Accreditation (SLMTA) programme has been implemented widely
      throughout Africa, as well as in the Caribbean, Central and South America, and
      Southeast Asia. OBJECTIVE: We compiled results from local, national and global
      studies to provide a broad view of the programme and identify directions for the
      future. The review consists of two companion papers; this paper focuses on
      content analysis, examining various thematic components of the SLMTA programme
      and future priorities. METHODS: A systematic literature search identified 28
      published articles about implementing the SLMTA programme. Results for various
      components of the SLMTA programme were reviewed and summarised. RESULTS: Local
      and national studies provide substantial information on previous experiences with
      quality management systems; variations on SLMTA implementation; building human
      resource capacity for trainers, mentors and auditors; the benefits and
      effectiveness of various types of mentorship; the importance of management buy-in
      to ensure country ownership; the need to instill a culture of quality in the
      laboratory; success factors and challenges; and future directions for the
      programme. CONCLUSIONS: Local, national and global results suggest that the SLMTA
      programme has been overwhelmingly successful in transforming laboratory quality
      management. There is an urgent need to move forward in four strategic directions:
      progression (continued improvement in SLMTA laboratories), saturation (additional
      laboratories within countries that have implemented SLMTA), expansion
      (implementation in additional countries), and extension (adapting SLMTA for
      implementation beyond the laboratory), to lead to transformation of overall
      health systems and patient care.

PMID- 29043201
TI  - A comprehensive review of the SLMTA literature part 2: Measuring success.
AB  - BACKGROUND: Since its introduction in 2009, the Strengthening Laboratory
      Management Toward Accreditation (SLMTA) programme has been implemented in 617
      laboratories in 47 countries. OBJECTIVE: We completed a systematic review of the
      published literature on SLMTA. The review consists of two companion papers; this
      article examines quantitative evidence presented in the publications along with a
      meta-analysis of selected results. METHODS: We identified 28 published articles
      with data from SLMTA implementation. The SLMTA programme was evaluated through
      audits based on a standard checklist, which is divided into 12 sections
      corresponding to the 12 Quality System Essentials (QSEs). Several basic service
      delivery indicators reported by programmes were also examined. Results for
      various components of the programme were reviewed and summarised; a meta-analysis
      of QSE results grouped by the three stages of the quality cycle was conducted for
      126 laboratories in 12 countries. RESULTS: Global programme data show improved
      quality in SLMTA laboratories in every country, with average improvements on
      audit scores of 25 percentage points. Meta-analysis identified Improvement
      Management as the weakest stage, with internal audit (8%) and occurrence
      management (16%) showing the lowest scores. Studies documented 19% - 95%
      reductions in turn-around times, 69% - 93% reductions in specimen rejection
      rates, 76% - 81% increases in clinician satisfaction rates, 67% - 85%
      improvements in external quality assessment results, 50% - 66% decreases in
      nonconformities and 67% increases in staff punctuality. CONCLUSIONS: The wide
      array of results reported provides a comprehensive picture of the SLMTA programme
      overall, suggesting a substantive impact on provision of quality laboratory
      services and patient care. These comprehensive results establish a solid data
      driven foundation for program improvement and further expansion.

PMID- 29043202
TI  - Why have doctors stopped asking for autopsies? Will a different type of autopsy
      change this?

PMID- 29043203
TI  - Endomyocardial fibrosis.

PMID- 29043204
TI  - Autopsy findings of miliary tuberculosis in a renal transplant recipient.
AB  - Miliary tuberculosis is a lethal form of disseminated tuberculosis (TB), deriving
      its name from the millet-seed-sized granulomas in multiple organs. As TB still
      remains a leading cause of morbidity and mortality in India, its disseminated
      forms need to be diagnosed early to ensure more aggressive treatment at the
      earliest possible time. However, a considerable number of cases are missed ante
      mortem. We discuss the case of a 32-year-old immunocompromised, non-HIV patient
      with an ante-mortem diagnosis of pulmonary TB. However, multiple organ
      involvement by Mycobacterium tuberculosis was demonstrated on autopsy. This case
      highlights the role of autopsy as a research and learning tool, and prudential
      clinico-pathologic correlation, which will improve clinical outcomes in the
      future.

PMID- 29043205
TI  - An extremely rare case of concurrent BRAF V600E mutation driven hairy cell
      leukemia and melanoma: case report and review of literature.
AB  - BRAF protein is a serine/threonine kinase with 766 amino acids. Approximately 15%
      of human cancers harbor BRAF mutations as well as other BRAF anomalies
      (amplifications, fusions). Somatic mutations mainly occur in the catalytic kinase
      domain (CR3), and the predominant mutation is p.V600E which is the substitution
      of glutamic acid (E) for valine (V) as result of a mutation at codon 600 of the
      kinase domain. To our knowledge, the vast majority of the cancers have non
      germline BRAF mutations. Here we describe a case of a 60-year-old female with a
      history of hairy cell leukemia (HCL) who presented with aphasia and
      forgetfulness. A follow-up Brain CT scan showed three distinct brain lesions
      which were found to be diagnostic of melanoma (confirmed by immunohistochemistry)
      with no evidence of a concurrent brain involvement by a B-cell neoplasm.
      Molecular studies confirmed the same BRAF p.V600E mutation in both malignancies
      (hairy cell leukemia and melanoma). Thereafter the patient was started on BRAF
      inhibitor treatment and is now symptom-free after one year of follow up. Having
      two concurrent malignancies with a shared BRAF mutation is extremely rare and
      makes this an excellent example of a genomic marker-driven treatment in two
      histologically and immunophenotypically distinct tumors.

PMID- 29043206
TI  - Spontaneous regression of a pulmonary adenocarcinoma after core needle biopsy.
AB  - Spontaneous regression (SR) of cancer, especially lung cancer, is a rare
      biological event with a mechanism that is not currently understood. Immunological
      mechanisms seem to be the stronger explanation in SR of a lung cancer. We report
      the rare case of SR of a lung adenocarcinoma stage IA, in a 75-year-old man,
      which was incidentally diagnosed and histologically confirmed. Due to the
      patient's comorbidities and his poor pulmonary function, stereotactic
      radiotherapy was scheduled. However, by the time the treatment was due to start,
      the tumor was no longer detectable.

PMID- 29043207
TI  - Mantle cell lymphoma: involvement of nodal and extranodal sites in the head and
      neck, with multifocal oral lesions.
AB  - Mantle cell lymphoma (MCL) is a malignant B-cell neoplasm, which comprises
      monomorphic and small- to medium-sized mantle zone-derived lymphoid cells. It is
      characterized by chromosomal translocation t(11;14)(q13;q32) and CCND1
      truncation, resulting in cell cycle deregulation. It is an aggressive type of non
      Hodgkin lymphoma with a propensity to present with extranodal involvement. This
      study shows the case of an 80-year-old Caucasian male who complained of a 2-month
      progressive swelling on the right side of his face. The magnetic resonance
      imaging exam showed multifocal involvement of the head and neck, including oral
      manifestations, bilateral parotid glands, palate, tongue, and floor of the mouth.
      An incisional biopsy of the tumor mass was performed. The morphological and
      immunophenotypic findings were consistent with the diagnosis of MCL. The patient
      died 4 months later, without any chance of undergoing a therapeutic approach.
      Although MCL is a rare condition, it should be subjected to a differential
      diagnosis when affecting the maxillofacial area. Imaging exams and both
      immunohistochemical and morphological analyses are needed to reach the correct
      diagnosis. Here, we present an unusual MCL with multifocal involvement of the
      head and neck.

PMID- 29043208
TI  - Phosphaturic mesenchymal tumor (PMT): exceptionally rare disease, yet crucial not
      to miss.
AB  - Phosphaturic mesenchymal tumors (PMTs) are very rare tumors which are frequently
      associated with Tumor Induced Osteomalacia (TIO), a paraneoplastic syndrome that
      manifests as renal phosphate wasting. The tumor cells produce a peptide hormone
      like substance known as fibroblast growth factor 23 (FGF23), a physiologic
      regulator of phosphate levels. FGF23 decreases proximal tubule reabsorption of
      phosphates and inhibits 1-alpha-hydroxylase, which reduces levels of 1-alpha, 25
      dihydroxyvitamine D3. Thus, overexpression of FGF23 by the tumor cells leads to
      increased excretion of phosphate in the urine, mobilization of calcium and
      phosphate from bones, and the reduction of osteoblastic activity, ultimately
      resulting in widespread osteomalacia. Patients typically present with gradual
      muscular weakness and diffuse bone pain from pathologic fractures. The diagnosis
      is often delayed due to the non-specific nature of the symptoms and lack of
      clinical suspicion. While serum phosphorus and FGF23 testing can assist in making
      a clinical diagnosis of PMT, the responsible tumor is often difficult to locate.
      The pathologic diagnosis is often missed due to the rarity of PMTs and histologic
      overlap with other mesenchymal neoplasms. While patients can experience severe
      disabilities without treatment, excision is typically curative and results in a
      dramatic reversal of symptoms. Histologically, PMT has a variable appearance and
      can resemble other low grade mesenchymal tumors. Even though very few cases of
      PMT have been reported in the world literature, it is very important to consider
      this diagnosis in all patients with hypophosphatemic osteomalacia. Here we
      present a patient who suffered for almost 5 years without a diagnosis.
      Ultimately, the PMT was located on a 68Ga-DOTA TATE PET/CT scan and subsequently
      confirmed by histologic and immunohistologic study. Interestingly, strong
      positivity for FGFR1 by IHC might be related to the recently described FN1-FGFR1
      fusion. Upon surgical removal, the patient's phosphate and FGF23 levels returned
      to normal and the patient's symptoms resolved.

PMID- 29043209
TI  - Perianal Langerhans cell histiocytosis: a rare presentation in an adult male.
AB  - Langerhans cell histiocytosis (LCH) is a rare disease characterized by a
      proliferation of cells that show immunophenotypic and ultrastructural
      similarities with antigen-presenting Langerhans cells of mucosal sites and skin.
      LCH in adults is rare, and there are still many undiagnosed/misdiagnosed
      patients. We describe LCH involvement of the perianal region of a 33-year-old
      male with a previous history of diabetes insipidus. The differential diagnosis
      and all the reported cases of LCH of the perianal skin involvement since its
      description in 1984 till 2016 are discussed. LCH should be considered in the
      differential diagnosis of perianal ulceration, especially in young patients where
      topical drug treatment has failed. The history of previous central diabetes
      insipidus of unknown etiology demands imaging studies in order to rule out
      central involvement of the disease.

PMID- 29043210
TI  - Pulmonary placental transmogrification associated with adenocarcinoma of the
      lung: a case report with a comprehensive review of the literature.
AB  - Pulmonary placental transmogrification (PT) is a rare entity with less than 40
      cases reported in the literature. Most reported cases are associated with either
      bullous emphysema or with pulmonary fibrochondromatous hamartomas. We present
      only the second case of PT associated with adenocarcinoma of the lung. A 67-year
      old female with multiple chronic medical ailments presented with shortness of
      breath and was found to have a 6-cm mass in the upper lobe of her right lung. A
      computed tomography (CT) guided core biopsy was performed that showed a well
      differentiated adenocarcinoma. Interestingly the normal lung tissue showed
      placental villous architecture. A unique feature of our case is that the
      diagnosis was made on a needle core biopsy, unlike all the other cases in the
      literature. We also provide a comprehensive review of this rare entity.

PMID- 29043211
TI  - Native-valve endocarditis caused by Achromobacter xylosoxidans: a case report and
      review of literature.
AB  - Achromobacter xylosoxidans is a Gram-negative aerobic bacterium first described
      by Yabuuchi and Ohyama in 1971. A. xylosoxidans is frequently found in aquatic
      environments. Abdominal, urinary tract, ocular, pneumonia, meningitis, and
      osteomyelitis are the most common infections. Infective endocarditis is rare. As
      far as we know, until now, only 19 cases have been described, including this
      current report. We report the case of community-acquired native valve
      endocarditis caused by A. xylosoxidans in an elderly patient without a
      concomitant diagnosis of a malignancy or any known immunodeficiency. The patient
      presented with a 2-month history of fever, weight loss, and progressive dyspnea.
      On physical examination, mitral and aortic murmurs were present, along with
      Janeway's lesions, and a positive blood culture for A. xylosoxidans. The
      transesophageal echocardiogram showed vegetation in the aortic valve, which was
      consistent with the diagnosis of infective endocarditis.

PMID- 29043212
TI  - Antibacterial, Anti-Diarrhoeal, Analgesic, Cytotoxic Activities, and GC-MS
      Profiling of Sonneratia apetala (Buch.-Ham.) Seed.
AB  - Fruits of Sonneratia apetala (Buch.-Ham.), (English: mangrove apple, Bengali:
      keora) both seeds and pericarps, are largely consumed as food besides their
      enormous medicinal application. The fruit seeds have high content of nutrients
      and bioactive components. The seeds powder of S. apetala was successively
      fractionated using n-hexane, diethyl ether, chloroform, ethyl acetate, and
      methanol. The fractions were used to evaluate antibacterial, anti-diarrhoeal,
      analgesic, and cytotoxic activities. Methanol fraction of seeds (MeS) stronly
      inhibited Escherichia coli strains, Salmonella Paratyphi A, Salmonella Typhi,
      Shigella dysenteriae, and Staphylococcus aureus except Vibrio cholerae at 500
      MUg/disc. All the fractions strongly inhibited castor oil induced diarrhoeal
      episodes and onset time in mice at 500 mg extract/kg body weight (P<0.001). At
      the same concentration, MeS had the strongest inhibitory activity on diarrhoeal
      episodes, whereas the n-hexane fraction (HS) significantly (P<0.05) prolonged
      diarrhoeal onset time as compared to positive control. Similarly, HS (P<0.005)
      inhibited acetic acid induced writhing in mice at 500 mg extract/kg, more than
      any other fraction. HS and diethyl ether fractions of seed strongly increased
      reaction time of mice in hot plate test at 500 mg extract/kg. All the fractions
      showed strong cytotoxic effects in brine shrimp lethality tests. Gas
      chromatography-mass spectrometry analysis of HS led to the identification of 23
      compounds. Linoleic acid (29.9%), palmitic acid (23.2%), ascorbyl palmitate
      (21.2%), and stearic acid (10.5%) were the major compounds in HS. These results
      suggest that seeds of S. apetala could be of great use as nutraceuticals.

PMID- 29043213
TI  - Sargassum yezoense Extract Inhibits Carbohydrate Digestive Enzymes In Vitro and
      Alleviates Postprandial Hyperglycemia in Diabetic Mice.
AB  - In this study, we investigated whether Sargassum yezoense extract (SYE) could
      inhibit alpha-glucosidase and alpha-amylase activities, and alleviate
      postprandial hyperglycemia in streptozotocin (STZ)-induced diabetic mice. Freeze
      dried S. yezoense was extracted with 80% ethanol and concentrated for use in this
      study. The hypoglycemic effect was determined by evaluating the inhibitory
      activities of SYE against alpha-glucosidase and alpha-amylase as well as its
      ability to decrease postprandial blood glucose levels. The half-maximal
      inhibitory concentrations of SYE against alpha-glucosidase and alpha-amylase were
      0.078+/-0.004 and 0.212+/-0.064 mg/mL, respectively. SYE was a more effective
      inhibitor of alpha-glucosidase and alpha-amylase activities than the positive
      control, acarbose. The increase in postprandial blood glucose levels was
      significantly alleviated in the SYE group compared with that in the control group
      of STZ-induced diabetic mice. Furthermore, the area under the curves
      significantly decreased with SYE administration in STZ-induced diabetic mice.
      These results suggest that SYE is a potent inhibitor of alpha-glucosidase and
      alpha-amylase activities and alleviates postprandial hyperglycemia caused by
      dietary carbohydrates.

PMID- 29043214
TI  - Vitamin A Improves Hyperglycemia and Glucose-Intolerance through Regulation of
      Intracellular Signaling Pathways and Glycogen Synthesis in WNIN/GR-Ob Obese Rat
      Model.
AB  - Vitamin A and its metabolites modulate insulin resistance and regulate stearoyl
      CoA desaturase 1 (SCD1), which are also known to affect insulin resistance. Here,
      we tested, whether vitamin A-mediated changes in insulin resistance markers are
      associated with SCD1 regulation or not. For this purpose, 30-week old male lean
      and glucose-intolerant obese rats of WNIN/GR-Ob strain were given either a stock
      or vitamin A-enriched diet, i.e. 2.6 mg or 129 mg vitamin A/kg diet, for 14
      weeks. Compared to the stock diet, vitamin A-enriched diet feeding improved
      hyperglycemia and glucose-clearance rate in obese rats and no such changes were
      seen in lean rats receiving identical diets. These changes were corroborated with
      concomitant increase in circulatory insulin and glycogen levels of liver and
      muscle (whose insulin signaling pathway genes were up-regulated) in obese rats.
      Further, the observed increase in muscle glycogen content in these obese rats
      could be explained by increased levels of the active form of glycogen synthase,
      the key regulator of glycogen synthesis pathway, possibly inactivated through
      increased phosphorylation of its upstream inhibitor, glycogen synthase kinase.
      However, the unaltered hepatic SCD1 protein expression (despite decreased mRNA
      level) and increased muscle-SCD1 expression (both at gene and protein levels)
      suggest that vitamin A-mediated changes on glucose metabolism are not associated
      with SCD1 regulation. Chronic consumption of vitamin A-enriched diet improved
      hyperglycemia and glucose-intolerance, possibly, through the regulation of
      intracellular signaling and glycogen synthesis pathways of muscle and liver, but
      not associated with SCD1.

PMID- 29043215
TI  - Inhibitory Effect of Hizikia fusiformis Solvent-Partitioned Fractions on Invasion
      and MMP Activity of HT1080 Human Fibrosarcoma Cells.
AB  - Matrix metalloproteinases (MMPs) are endopeptidases that take significant roles
      in extracellular matrix degradation and therefore linked to several complications
      such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis.
      Hizikia fusiformis, a brown algae, was reported to possess bioactivities,
      including but not limited to, antiviral, antimicrobial, and anti-inflammatory
      partly due to bioactive polysaccharide contents. In this study, the potential of
      H. fusiformis against cancer cell invasion was evaluated through the MMP
      inhibitory effect in HT1080 fibrosarcoma cells in vitro. H. fusiformis crude
      extract was fractionated with organic solvents, H2O, n-BuOH, 85% aqueous MeOH,
      and n-hexane (n-Hex). The non-toxicity of the fractions was confirmed by MTT
      assay. All fractions inhibited the enzymatic activities of MMP-2 and MMP-9
      according to the gelatin zymography assay. Cell migration was also significantly
      inhibited by the n-Hex fraction. In addition, both gene and protein expressions
      of MMP-2 and -9, and tissue inhibitor of MMPs (TIMPs) were evaluated by reverse
      transcription-polymerase chain reaction and Western blotting, respectively. The
      fractions suppressed the mRNA and protein levels of MMP-2, MMP-9 while elevating
      the TIMP-1 and TIMP-2, with the H2O fraction being the least effective while n
      Hex fraction the most. Collectively, the n-Hex fraction from brown algae H.
      fusiformis could be a potential inhibitor of MMPs, suggesting the presence of
      various derivatives of polysaccharides in high amounts.

PMID- 29043216
TI  - Proximate, Phytochemical, and In Vitro Antimicrobial Properties of Dried Leaves
      from Ocimum gratissimum.
AB  - Ocimum gratissimum is a common plant in the tropics and has been used in food and
      medicine. Its usage in food and medicine could be attributed to its phtyochemical
      and antimicrobial properties. In this study we investigated the proximate,
      phytochemical, and antimicrobial attributes of air dried leaves of O.
      gratissimum. The aqueous extract was found to contain phtyochemicals with
      alkaloid and saponin present in appreciable amounts. The proximate analysis
      (crude protein and crude fibre content were 15.075% and 17.365%, respectively)
      showed that the leaf could be a good source of protein and fibre. The aqueous
      ethanolic extract of the leaf exhibited activity against a wider range of
      organisms when compared to the aqueous extract at the investigated
      concentrations. Aqueous ethanolic extracts of O. gratissimum leaf was active
      against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and
      Bacillus cereus and the aqueous extract of the leaf was active against P.
      aeruginosa.

PMID- 29043217
TI  - Antioxidant and Antimicrobial Activities of Quinoa (Chenopodium quinoa Willd.)
      Seeds Cultivated in Korea.
AB  - The objective of this study was to investigate the antioxidant and antimicrobial
      properties of quinoa cultivated in Korea and to compare it with imported quinoa
      from the USA and Peru. The highest amount of total flavonoid contents (TFC) with
      20.91 mg quercetin equivalents/100 g was measured in quinoa seed extract
      cultivated in Korea, while the total phenolic contents (TPC) were significantly
      higher in quinoa from the USA (16.28 mg gallic acid equivalents/100 g). In
      addition, quinoa extracts cultivated in Korea displayed a superior antioxidant
      ability in both, ferric reducing antioxidant power and 1,1-diphenyl-2
      picrylhydrazyl values. There was a high correlation between TFC and antioxidant
      activity and a low correlation between TPC and antioxidant activity. The
      antimicrobial activity of the quinoa extracts was determined using a disc
      diffusion assay and optical density method. In both assays, the quinoa seed
      extracts did not have strong antimicrobial activity against foodborne bacteria,
      including Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus,
      Escherichia coli, Salmonella Typhimurium, and Campylobacter jejuni.

PMID- 29043218
TI  - Evaluation of Antioxidant and Antimicrobial Activities of Ethanol Extracts of
      Three Kinds of Strawberries.
AB  - The antioxidant and antimicrobial activities of three kinds of strawberry ethanol
      extracts from Robus corchorifolius L. f. (RCL), Rubus parvifolius L. var.
      parvifolius (RPL), and Duchesnea chrysantha Miq. (DCM) were investigated. The RPL
      was highest (P<0.05) in phenolic, flavonoid, and anthocyanin contents. 2,2
      Diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic
      acid) radical scavenging activities of RPL and DCM extracts were higher than that
      of RCL (P<0.05). Hydrogen peroxide scavenging activity of RPL was high compared
      to DCM and RCL (P<0.05). RCL exhibited a significant (P<0.05) potent antioxidant
      activity in nitric oxide radical inhibition. Inhibition diameter zone (nearest
      mm) of extracts against the test bacteria ranged from 11.5 in RCL to 12.5 in DCM
      against Staphylococcus aureus, from 10.5 in RCL to 13.5 in DCM against
      Streptococcus pneumoniae, from 8.5 in DCM to 10.5 in RCL against Escherichia
      coli, and the same inhibition of 10 mm in three of the extracts against
      Klebsiella pneumoniae. However, there was no inhibition against fungi Aspergillus
      niger and Candida albicans. Three of the extracts had the same minimum inhibitory
      concentration values of 12.50, 12.50, and 6.25 MUg/mL against S. aureus, K.
      pneumoniae, and S. pneumoniae, respectively. On the other hand, MIC values of
      12.50, 12.50, and 6.50 MUg/mL were recorded for RPL, DCM, and RCL against E.
      coli, respectively. The result of present study revealed that extracts from three
      kinds of strawberries could be potential candidates as antioxidant and
      antimicrobial sources for functional food industries.

PMID- 29043219
TI  - Optimization of Maillard Reaction between Glucosamine and Other Precursors by
      Measuring Browning with a Spectrophotometer.
AB  - The individual Maillard reactions of glucose, glucosamine, cyclohexylamine, and
      benzylamine were studied at a fixed temperature of 120 degrees C under different
      durations by monitoring the absorbance of the final products at 425 nm.
      Glucosamine was the most individually reactive compound, whereas the reactions of
      glucose, cyclohexylamine, and benzylamine were not significantly different from
      each other. Maillard reactions of reaction mixtures consisting of glucosamine
      cyclohexylamine, glucosamine-benzylamine, glucose-cyclohexylamine, and glucose
      benzylamine were also studied using different concentration ratios under
      different durations at a fixed temperature of 120 degrees C and pH 9. Maillard
      reactions in the pairs involving glucosamine were observed to be more intense
      than those of the pairs involving glucose. Finally, with respect to the
      concentration ratios, it was observed that in most instances, optimal activity
      was realized, when the reaction mixtures were in the ratio of 1:1.

PMID- 29043220
TI  - Enhancement of Antioxidant Quality of Green Leafy Vegetables upon Different
      Cooking Method.
AB  - Antioxidant rich green leafy vegetables including garden spinach leaf, water
      spinach leaf, Indian spinach leaf, and green leaved amaranth were selected to
      evaluate the effects of water boiling and oil frying on their total phenolic
      content (TPC), total flavonoid content (TFC), reducing power (RP), and
      antioxidant capacity. The results revealed that there was a significant increase
      in TPC, TFC, and RP in all the selected vegetables indicating the effectiveness
      of the cooking process on the antioxidant potential of leafy vegetables. Both
      cooking processes enhanced significantly (P<0.05) the radical scavenging ability,
      especially the oil fried samples showed the highest values. There is a
      significant reduction in the vitamin C content in all the vegetables due to
      boiling and frying except in the Indian spinach leaf. However, the present
      findings suggest that boiling and frying can be used to enhance the antioxidant
      ability, by increasing the bioaccessibility of health-promoting constituents from
      the four vegetables investigated in this study.

PMID- 29043221
TI  - Effects of Extraction Methods on In Vitro Biological Capacities and Rheological
      Properties of Polysaccharides from Red Pepper Stems.
AB  - The purposes of this study were to produce polysaccharides from red pepper stems
      using different extraction methods and evaluate their chemical composition, in
      vitro biological capacities, and rheological properties. Two polysaccharides were
      extracted from red pepper stems using an autoclave and alkali treatments, and the
      extracts were named PAU and PAL, respectively. The contents of total phenolics
      and flavonoids were significantly higher in PAU than those in PAL. PAU exhibited
      greater scavenging activities on 2,2-diphenyl-1-picrylhydrazyl radicals, 2,2'
      azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radicals,
      superoxide radicals, and nitrite compared to PAL, suggesting that PAU served as
      better antioxidants. Similarly, in vitro inhibitory abilities against
      carbohydrate hydrolyzing enzymes of PAU were higher than those of PAL. Steady
      shear rheological analysis demonstrated that PAU showed higher psuedoplastic
      shear-thinning behavior compared to PAL. Based on the results from dynamic shear
      rheological properties, it was found that both samples had predominantly viscous
      behavior rather than elastic behavior.

PMID- 29043222
TI  - Production of Fermented Kale Juices with Lactobacillus Strains and Nutritional
      Composition.
AB  - Fermented kale juices using four types of lactobacilli were produced in the
      present study. After 48 h of fermentation time, viable cell counts of all
      ferments reached an above 109 CFU/mL. The viability of the ferments after cold
      storage in the refrigerator for 4 weeks showed 108 CFU/mL in all ferments. Among
      four types of fermented kale juices, the ferment of Lactobacillus acidophilus IFO
      3025 indicated a good nutritional composition, including neutral sugar (1,909.76
      MUg/mL), reducing sugar (564.00 MUg/mL, P<0.05), and protein contents (160.06
      MUg/mL, P<0.05). The results of mineral composition analysis had the highest
      potassium value in all ferments (854.16~895.07 MUg/mL), particularly in the
      ferment of Lactobacillus brevis FSB-1 (P<0.001), which is necessary to sustain
      osmotic pressure, prevention of high blood pressure, and protein synthesis.
      Moreover, calcium, phosphorus, and magnesium contents related to bone health were
      generally sufficient in all ferments. Consequently, in this study, fermented kale
      juices may be suggested as a healthy fermented beverage with essential nutrients.
      However, the acceptability of the fermented kale juice to the Korean taste should
      be further investigated with a trained taste panel to determine whether
      inoculated fermentation could be an option for the consumers.

PMID- 29043223
TI  - Amygdalin Contents in Peaches at Different Fruit Development Stages.
AB  - Amygdalin contents of the seeds, endocarps, and mesocarps from three peach
      cultivars (i.e., Stone Peach, Hikawa Hakuho, and Bakhyang) were measured at three
      stages of fruit development (stone-hardening, fruit enlargement, and ripening).
      The peach samples were dried and defatted with a Soxhlet apparatus, reflux
      extracted with methanol, and analyzed using reverse phase high-performance liquid
      chromatography. During all fruit development stages, the amygdalin contents in
      the seeds were higher than those in the endocarps and mesocarps. The amygdalin
      contents of the Stone Peach were comparatively higher than the Hikawa Hakuho and
      Bakhyang (P<0.05). Further, the amygdalin contents during ripening were very low
      or not detected. Overall, the amygdalin contents of the three peach cultivar
      samples (seed, endocarp, and mesocarp) increased until the fruit enlargement
      stage and either remained constant or decreased during ripening.

PMID- 29043224
TI  - Optimization of Mixing Ratio to Improve Antioxidant Activity of Aged Garlic with
      Pine Needle Using Response Surface Methodology.
AB  - Aged garlic has been reported to possess beneficial pharmacological activities,
      including anti-stress and anti-fatigue properties, and to exert protective
      effects on the cardiovascular system and liver. Pine needles are widely used in
      folk medicine and as food additives owing to their pharmacological properties
      such as anti-aging and anti-inflammatory effects. It has long been known that
      combining certain phytochemicals with other phenols or organic acids can produce
      synergistic effects. Therefore, the purpose of this study was to develop an
      optimal formula of aged garlic with added pine needle powder for improved
      antioxidant activity using the statistical technique of response surface
      methodology. The antioxidant activities of aged garlic mixed with pine needle
      powder were confirmed by measuring oxygen radical absorbance capacity and total
      polyphenol content. An optimized antioxidant formula was identified that
      contained 5.08 g aged garlic and 1.97 g pine needle powder. The antioxidant
      activities of the mixture prepared using this optimal formula were significantly
      higher than the predicted values according to an additive model. Hence, this
      study confirms that the addition of pine needle powder to aged garlic can improve
      its antioxidant activity. This study demonstrated an optimal mixing ratio to
      produce an aged garlic product with improved functionality through the addition
      of pine needle powder that could be successfully employed by the food industry to
      prepare functional foods.

PMID- 29043225
TI  - Physicochemical and Textural Properties of Noodles Prepared from Different Potato
      Varieties.
AB  - This study was performed to investigate the quality characteristics of noodles
      made from four different potato varieties: Atlantic, Go-un, Sae-bong, Jin-sun,
      and wheat flour. Quality characteristics of five noodles were analyzed by general
      components analysis, cooking quality (rate of water absorption, cooking loss, and
      volume increase), and mechanical textural properties. Some variations existed in
      wheat- or potato-based noodles for the general components analysis, but no clear
      trend was observed. Higher values in the rates of water absorption, cooking loss,
      and volume increase were observed for the wheat flour noodle, while some
      variations were observed for potato noodles depending on the variety. The wheat
      flour noodles exhibited higher values of textural characteristics obtained from
      the texture profile analysis, except for adhesiveness. Higher gluten contents as
      well as lower ash contents in the wheat flour noodles compared to the potato
      noodles are thought to be the two key factors contributing to this finding.

PMID- 29043226
TI  - Invasive fungal infection (IFI) in pediatric leukemia: better outcome with ACT.

PMID- 29043227
TI  - The role of cord blood banks in the cell therapy era: future perspectives.

PMID- 29043228
TI  - Auer rods in unusual sites: macrophage indigestion.

PMID- 29043229
TI  - Blastic plasmacytoid dendritic cell neoplasm in the CSF.

PMID- 29043230
TI  - Advances in the treatment of newly diagnosed primary central nervous system
      lymphomas.
AB  - Primary central nervous system lymphoma (PCNSL) is a type of highly invasive non
      Hodgkin lymphoma. With a growing number of organ transplantation and
      immunosuppressant therapy, the incidence of PCNSL has been growing rapidly in
      recent years, which is attributed to the increased incidence of HIV/AIDS, a
      prominent risk factor for developing PCNSL. The rising rate of PCNSL incidence is
      the highest among the intracranial tumors. In the past 20 years, dozens of
      clinical trials related to PCNSL have been registered, but adequate therapeutics
      are still challenging. Currently, the chemotherapy regimens based on high-dose
      methotrexate and whole-brain radiotherapy are the two main therapeutic options;
      however, the toxicity associated with those is the main problem that challenges
      medical researchers. Novel agents and therapeutic strategies have been developed
      in recent years. In the current review, we describe advances in the treatment of
      PCNSL and discuss novel therapeutic approaches currently in development, such as
      the use of rituximab, disruption of the blood-brain barrier, and state-of-the-art
      radiotherapy.

PMID- 29043231
TI  - Voriconazole plus caspofungin for treatment of invasive fungal infection in
      children with acute leukemia.
AB  - BACKGROUND: Invasive fungal infections (IFIs) are a life-threatening problem in
      immunocompromised patients. Despite timely diagnosis and appropriate antifungal
      therapy, clinical outcomes of IFIs remain unsatisfactory, necessitating treatment
      with a combination of antifungal agents. Therefore, childhood leukemic patients
      treated with voriconazole plus caspofungin were evaluated for the safety and
      efficacy of the combination antifungal therapy to treat IFIs. METHODS: In this
      retrospective study, medical records were retrieved for patients admitted to the
      Pediatric Department of Yeungnam University Hospital, Daegu, South Korea, between
      April 2009 and May 2013. Medical records of 22 patients were analyzed. RESULTS:
      Of the 22 patients studied, nine (41%) had been diagnosed with probable IFI, and
      13 (59%) with possible IFI. All patients, except one, were already receiving
      antifungal monotherapy for the treatment of neutropenic fever. After a diagnosis
      of IFI was confirmed, antifungal monotherapy was replaced with combination
      therapy. The study's overall response rate was 90.9%, with complete responses in
      86.3% of the patients. Two patients experienced a side effect of a small increase
      in liver enzyme levels. CONCLUSION: Voriconazole plus caspofungin combination
      therapy is an effective and safe treatment for serious IFI in pediatric patients
      with acute leukemia.

PMID- 29043232
TI  - Comparison of the effects of early intensified induction chemotherapy and
      standard 3+7 chemotherapy in adult patients with acute myeloid leukemia.
AB  - BACKGROUND: Standard remission induction chemotherapy consisting of anthracycline
      plus cytarabine (3+7) is administered for adult acute myeloid leukemia (AML).
      However, the effects of intensified regimen on complete remission (CR), relapse
      and overall survival (OS) remain unknown. METHODS: We analyzed 1195 patients
      treated with idarubicin plus cytarabine/BHAC (3+7) from 2002 to 2013. Among them,
      731 received early intensification with 3-day cytarabine/BHAC (3+10, N=363) or 2
      day idarubicin plus cytarabine/BHAC 3 days (5+10, N=368). The 3+10 and 5+10
      strategies were applied to patients with bone marrow blast counts of 5-20% and
      >20% on day 7 of 3+7, respectively. RESULTS: Early intensification correlated
      with a younger age (median: 40 vs. 45 yr) and higher t(8;21) frequency (20.4% vs.
      7.1%), compared to 3+7. After early intensification, the early death rates were
      higher among the elderly (3+10 [15.7%], 5+10 [21.7%] vs. 3+7 [6.3%], P=0.038),
      while the post-induction CR rate was higher in young patients (3+10 [79.8%], 5+10
      [75.1%] vs. 3+7 [65.1%], P<0.001). Early relapse rate was also decreased (3+10
      [11.8%], 5+10 [11.7%] vs. 3+7 [22.0%], P<0.001). In multivariate analysis, early
      intensification correlated with an inferior 5-year OS among elderly patients
      (19.2% vs. 22.8%; hazard ratio [HR]=1.84, 95% confidence interval [CI]; 1.11
      3.06, P=0.018) and lower overall relapse rate among young patients (33.0% vs.
      41.4%, P=0.023; HR=0.71, 95% CI; 0.55-0.93, P=0.012). CONCLUSION: Early
      intensification correlated with higher CR and lower relapse rates, but not OS in
      young AML patients. In elderly patients, early intensification correlated with a
      higher early death rate and poorer OS.

PMID- 29043233
TI  - Clinical characteristics and treatment outcomes of isolated myeloid sarcoma
      without bone marrow involvement: a single-institution experience.
AB  - BACKGROUND: Isolated myeloid sarcoma (MS) is a rare extramedullary tumor mass
      composed of malignant myeloid precursor cells without any evidence of leukemia in
      the peripheral blood and bone marrow. We describe the clinical characteristics
      and outcomes of patients diagnosed with isolated MS at our institution. METHODS:
      We retrospectively reviewed 9 of 497 acute myeloid leukemia (AML) patients (1.8%)
      with isolated MS. Isolated MS patients were divided into 2 groups according to
      the first-line treatment strategy: systemic treatment only (S) or local treatment
      with or without systemic treatment (LS). RESULTS: The most common site of MS
      occurrence was the head and neck area (N=4, 44.4%), followed by the anterior
      mediastinum (N=2, 22.2%) and the gastrointestinal tract (N=2, 22.2%). The tumors
      of 4 patients (44.4%) eventually evolved to AML, in a median time of 13.4 months
      (range, 2.4-20.1 mo). The number of patients achieving complete remission after
      first-line treatment was higher in the LS group (N=5, 83.3%) than in the S group
      (N=1, 33.3%) (P =0.226). All patients in the LS group survived, but those in the
      S group died (P=0.012). CONCLUSION: Accurate and rapid diagnosis using various
      modalities and the early initiation of intensive combined treatment may be the
      optimal strategies to reduce the risk of isolated MS subsequently evolving to
      AML. To fully understand the characteristics of isolated MS, a larger number of
      patients from a multinational study is necessary.

PMID- 29043234
TI  - Clinical impact of CD5 expression in Korean patients with diffuse large B-cell
      lymphoma.
AB  - BACKGROUND: CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) accounts for
      5-10% of DLBCL cases and has poor patient outcomes. However, most studies on CD5+
      DLBCL were performed in Japanese patients and only few data are available for
      Korean population. In this study, we investigated the clinical characteristics
      and prognostic impact of CD5 expression in Korean patients with bone marrow (BM)
      involvement of DLBCL. METHODS: Patients who were initially diagnosed with BM
      involvement of de novo DLBCL from 2005 to 2013 were included. Clinicopathological
      features and outcomes of patients were compared between CD5+ and CD5 negative
      (CD5-) DLBCL. RESULTS: Among a total of 57 patients, the number of patients with
      CD5+ and CD5- DLBCL were 13 and 44, respectively. Clinical and laboratory
      features of CD5+ DLBCL were not significantly different from those of CD5- DLBCL.
      The 3-year overall survival (OS) rates for CD5+ and CD5- DLBCL were 20.2% and
      59.0%, respectively (P=0.031), and 3-year progression-free survival (PFS) rates
      for CD5+ and CD5- DLBCL were 23.1% and 50.1%, respectively (P=0.055). CONCLUSION:
      CD5+ DLBCL with BM involvement showed an inferior survival tendency compared to
      CD5- DLBCL, and thorough evaluation of CD5 expression might be helpful to predict
      the prognosis of patients with DLBCL.

PMID- 29043235
TI  - Platelet to lymphocyte ratio (PLR) retains independent prognostic significance in
      advanced stage marginal zone lymphoma patients treated with rituximab,
      cyclophosphamide, vincristine, and prednisone combination chemotherapy (R-CVP):
      Consortium for Improving Survival of Lymphoma trial.
AB  - BACKGROUND: Rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP)
      is one of the effective chemotherapeutic regimens for patients with advanced
      stage marginal zone lymphoma (MZL). However, prognostic factors that affect the
      outcome of treatment for MZL are not well understood. METHODS: Between August
      2006 and June 2013, patients with newly diagnosed stage III and IV MZL treated
      with R-CVP as a first-line therapy from 15 institutions were retrospectively
      analyzed. Patients' clinical and laboratory data at diagnosis were collected by
      review of medical records. RESULTS: A total of 80 patients were analyzed. Bone
      marrow involvement was observed in 30% cases. Twelve patients (15%) had nodal
      MZL, and 41.3% patients exhibited multiple mucosa-associated lymphoma tissue
      sites. Overall response rate was 91.3%, including 73.8% achieving complete
      response. Advanced MZL patients treated with R-CVP showed a 3-year progression
      free survival (PFS) rate of 69.6%. Prognostic markers significantly affecting PFS
      in univariate analysis were platelet to lymphocyte ratio (PLR, <95 vs. >=95,
      P=0.014), serum albumin (<=3.9 vs. >3.9 g/dL, P=0.008), and the International
      Prognostic Index (IPI) score (1 vs. 2-4, P=0.032). In multivariate analysis, only
      PLR (<95 vs. >=95, HR 0.367, 95% CI, 0.139-0.971, P=0.043) was an independent
      risk factor for PFS. CONCLUSION: PLR >=95 at diagnosis is an independent
      prognostic marker for PFS in advanced stage MZL patients treated with R-CVP. This
      marker may aid clinicians in predicting the response to R-CVP chemotherapy in
      stage III and IV MZL patients.

PMID- 29043236
TI  - Efficacy of eculizumab in paroxysmal nocturnal hemoglobinuria patients with or
      without aplastic anemia: prospective study of a Korean PNH cohort.
AB  - BACKGROUND: Patients with paroxysmal nocturnal hemoglobinuria (PNH) often have
      concurrent aplastic anemia (AA). This study aimed to determine whether eculizumab
      treated patients show clinical benefit regardless of concurrent AA. METHODS: We
      analyzed 46 PNH patients >=18 years of age who were diagnosed by flow cytometry
      and treated with eculizumab for more than 6 months in the prospective Korean PNH
      registry. Patients were categorized into two groups: PNH patients with concurrent
      AA (PNH/AA, N=27) and without AA (classic PNH, N=19). Biochemical indicators of
      intravascular hemolysis, hematological laboratory values, transfusion
      requirement, and PNH-associated complications were assessed at baseline and every
      6 months after initiation of eculizumab treatment. RESULTS: The median patient
      age was 46 years and median duration of eculizumab treatment was 34 months.
      Treatment with eculizumab induced rapid inhibition of hemolysis. At 6-month
      follow-up, LDH decreased to near normal levels in all patients; this effect was
      maintained until the 36-month follow-up regardless of concurrent AA. Transfusion
      independence was achieved by 53.3% of patients within the first 6 months of
      treatment and by 90.9% after 36 months of treatment. The mean number of RBC units
      transfused was significantly reduced, from 8.5 units during the 6 months prior to
      initiation of eculizumab to 1.6 units in the first 6 months of treatment, for the
      total study population; this effect was similar in both PNH/AA and classic PNH.
      CONCLUSION: This study demonstrated that eculizumab is beneficial in the
      management of patients with PNH/AA, similar to classic PNH.

PMID- 29043237
TI  - Hepcidin and iron parameters in children with anemia of chronic disease and iron
      deficiency anemia.
AB  - BACKGROUND: Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are
      the two most prevalent forms of anemia having interrelated characteristics.
      Hepcidin, a newly introduced biomarker for assessment of iron status, is a
      homeostatic regulator of iron metabolism. We investigated the role of hepcidin
      and other conventional iron parameters to assess iron status among children with
      ACD and IDA. We also identified children with ACD who developed iron deficiency
      (ID). METHODS: The study was undertaken in anemic children with 30 cases each of
      ACD and IDA along with 30 age and sex-matched controls. The ACD cases were
      subdivided into pure ACD and ACD with coexistent ID. All cases were subjected to
      following tests: complete blood count with peripheral smear, serum C-reactive
      protein, serum interleukin-6, iron studies, serum soluble transferrin receptor
      (sTfR), and serum hepcidin. RESULTS: The mean serum hepcidin concentration was
      significantly increased in pure ACD patients (143.85+/-42.76 ng/mL) as compared
      to those in IDA patients (6.01+/-2.83 ng/mL, P < 0.001) and controls (24.96+/
      9.09 ng/mL, P <0.001). Also, compared to pure ACD patients [normal sTfR levels
      (<3 ug/mL)], the serum hepcidin concentration was reduced significantly in ACD
      patients with ID [high sTfR levels (>=3 ug/mL)] with a mean of 10.0+/-2.97 ng/mL.
      CONCLUSION: Hepcidin measurement can provide a useful tool for differentiating
      ACD from IDA and also help to identify an iron deficiency in ACD patients. This
      might aid in the appropriate selection of therapy for these patients.

PMID- 29043238
TI  - Hematologists and nephrologists working together: moving forward with a new
      integrated care model for blood-related malignancies?

PMID- 29043239
TI  - A case of synchronous multiple myeloma and chronic myeloid leukemia.

PMID- 29043240
TI  - Sequential heart and autologous stem cell transplantation for light-chain cardiac
      amyloidosis.

PMID- 29043241
TI  - An unusual case of metachronous NK/T cell lymphoma and interdigitating dendritic
      cell sarcoma.

PMID- 29043242
TI  - Primary adrenal T-cell lymphoma in a young adult presented with pseudo-hypopyon:
      a case report and literature review.

PMID- 29043243
TI  - Combined occurrence of Bernard-Soulier syndrome and prekallikrein deficiency.

PMID- 29043244
TI  - A case of adult-onset Still's disease accompanied by pseudo-gray platelet
      syndrome.

PMID- 29043245
TI  - Intentional partial odontectomy-a long-term follow-up study.
AB  - BACKGROUND: The surgical extraction of the third molar is the most frequently
      encountered procedure in oral and maxillofacial surgery and is related with a
      variety of complications. This study examined the efficacy of intentional partial
      odontectomy (IPO) in the third molars which have no periapical lesions and are
      located near important anatomical structures such as inferior alveolar nerve.
      METHODS: Seven patients (four males, three females, 39.1 +/- 11.6 years), who
      received IPO to reduce the risk of inferior alveolar nerve injury (IANI), were
      followed long-term. The treated teeth were horizontally impacted third molars in
      the mandibular left (n = 5) or mandibular right (n = 4) areas and were all
      ankylosed with the surrounding alveolar bone. During the IPO, the bone around the
      crown was removed to expose the crown, and then the tooth was resected at cement
      enamel junction (CEJ). Any secondary trauma to the healthy root was minimized and
      remained intact after primary suture. RESULTS: The mean follow-up time was 63.2
      +/- 29.8 months, and all sites showed good bone healing after the crown removal.
      Also, sensory abnormality was not found in any patients after IPO. In one
      patient, the bone fragments erupted 4 months after IPO. In other patient, an
      implant placed on second molar site adjacent to the third molar that received IPO
      was explanted about 2 years after the patient's persistent discomfort.
      CONCLUSIONS: In case where high risk of IANI exists, IPO may be chosen
      alternatively to surgical extraction to reduce the risk of nerve damage.

PMID- 29043246
TI  - Follow-up of Mothers with Suspected Postpartum Depression from Pediatrics
      Clinics.
AB  - PURPOSE: Pediatric providers are increasingly screening for postpartum depression
      (PD), yet, it is unknown how often mothers comply with recommendations to seek
      treatment. The objectives were to describe the rate at which mothers with
      suspected PD seek treatment and explore factors that predict help-seeking
      behavior. DESIGN AND METHODS: Mothers were recruited from four pediatric clinics
      after identification using the Child Health Improvement through Computer
      Automation (CHICA) system. Mothers with a positive screen were invited to
      participate in a telephone interview between January 2012 and December 2014.
      Mothers reported if they sought treatment or called a community resource.
      RESULTS: 73 of 133 eligible mothers participated (55% response rate). Fifty women
      recalled a recommendation to seek help. Only 43.8% (32/73) made a follow-up
      appointment with an adult provider and even fewer kept the appointment.
      CONCLUSION: A majority of mothers suspected of having PD recalled a referral for
      further intervention; yet, less than half took action. Further investigation of
      barriers of help-seeking behavior is warranted.

PMID- 29043247
TI  - Clinic-Based Mobile Health Decision Support to Enhance Adult Epilepsy Self
      Management: An Intervention Mapping Approach.
AB  - INTRODUCTION: Epilepsy is a neurological disorder involving recurrent seizures.
      It affects approximately 5 million people in the U.S. To optimize their quality
      of life people with epilepsy are encouraged to engage in self-management (S-M)
      behaviors. These include managing their treatment (e.g., adhering to anti-seizure
      medication and clinical visit schedules), managing their seizures (e.g.,
      responding to seizure episodes), managing their safety (e.g., monitoring and
      avoiding environmental seizure triggers), and managing their co-morbid conditions
      (e.g., anxiety, depression). The clinic-based Management Information Decision
      Support Epilepsy Tool (MINDSET) is a decision-support system founded on theory
      and empirical evidence. It is designed to increase awareness by adult patients
      (>=18 years) and their health-care provider regarding the patient's epilepsy S-M
      behaviors, facilitate communication during the clinic visit to prioritize S-M
      goals and strategies commensurate with the patient's needs, and increase the
      patient's self-efficacy to achieve those goals. METHODS: The purpose of this
      paper is to describe the application of intervention mapping (IM) to develop,
      implement, and formatively evaluate the clinic-based MINDSET prototype and in
      developing implementation and evaluation plans. Deliverables comprised a logic
      model of the problem (IM Step 1); matrices of program objectives (IM Step 2); a
      program planning document comprising scope, sequence, theory-based methods, and
      practical strategies (IM Step 3); a functional MINDSET program prototype (IM Step
      4); plans for implementation (IM Step 5); and evaluation (IM Step 6). IM provided
      a logical and systematic approach to developing and evaluating clinic-based
      decision support toward epilepsy S-M.

PMID- 29043248
TI  - Health by Design: Interweaving Health Promotion into Environments and Settings.
AB  - The important influence of the environmental context on health and health
      behavior-which includes place, settings, and the multiple environments within
      place and settings-has directed health promotion planners from a focus solely on
      changing individuals, toward a focus on harnessing and changing context for
      individual and community health promotion. Health promotion planning frameworks
      such as Intervention Mapping provide helpful guidance in addressing various
      facets of the environmental context in health intervention design, including the
      environmental factors that influence a given health condition or behavior,
      environmental agents that can influence a population's health, and environmental
      change methods. In further exploring how to harness the environmental context for
      health promotion, we examine in this paper the concept of interweaving of health
      promotion into context, defined as weaving or blending together health promotion
      strategies, practices, programs, and policies to fit within, complement, and
      build from existing settings and environments. Health promotion interweaving
      stems from current perspectives in health intervention planning, improvement
      science and complex systems thinking by guiding practitioners from a
      conceptualization of context as a backdrop to intervention, to one that
      recognizes context as integral to the intervention design and to the potential to
      directly influence health outcomes. In exploring the general approach of health
      promotion interweaving, we examine selected theoretical and practice-based
      interweaving concepts in relation to four key environments (the policy
      environment, the information environment, the social/cultural/organizational
      environment, and the physical environment), followed by evidence-based and
      practice-based examples of health promotion interweaving from the literature.
      Interweaving of health promotion into context is a common practice for health
      planners in designing health promotion interventions, yet one which merits
      further intentionality as a specific health promotion planning design approach.

PMID- 29043250
TI  - Canine Food Preference Assessment of Animal and Vegetable Ingredient-Based Diets
      Using Single-Pan Tests and Behavioral Observation.
AB  - Knowledge of canine food selection is critical for both the pet food industry and
      dog owners, since owners want quality foods that are palatable, while fulfilling
      their pet's nutritional requirements. There are two common methods for assessing
      canine food preference: the two-pan test and the one-pan test. Neither test fully
      accounts for the complexity of the canine feeding experience nor do they provide
      applicable representations of canine feeding behavior in the home. The objectives
      of this study were to (1) determine whether dogs display a preference for animal
      ingredient-based diets when compared with vegetable ingredient-based diets and
      (2) examine whether dogs experience neophobia when presented with a novel diet.
      Eight adult Beagles (average age = 24 months, weighing 8-12 kg) were individually
      fed each of four novel diets in a 4 * 4 replicated Latin square design, with 10-d
      treatment periods and four dietary treatments. Data were analyzed using a mixed
      model with repeated measures and significance was declared when p < 0.05. The
      diets were: animal and vegetable ingredient-based diets, and animal- and
      vegetable-based ingredients diluted with anhydrous alpha-d-glucose. The diluted
      diets were used for a larger study to determine true mineral digestibility. Dogs
      were fed twice per day (0800 and 1300 h). Behavioral observations were made by
      video on the first, and last 2 days of each 10-day treatment period of both a.m.
      and p.m. feedings. Time to consume feed, distraction, hesitation, level of
      anticipation pre-consumption, and interest post-consumption were recorded. Dogs
      experienced initial disruptive (neophobic) effects of a novel diet. Neophobia was
      demonstrated by a decreased (slower) rate of consumption, increased distraction
      during consumption of the diet, and increased hesitation on the first day of each
      new diet (p < 0.05). The level of interest post-consumption was highest when dogs
      consumed the animal-based ingredients diet (p < 0.05). This study presents
      insights into canine food preference assessment methods that may more accurately
      represent the dog owner's experience. Further research is required to determine
      the minimum length of time necessary to eliminate neophobia to food. In addition,
      future research should also aim to establish whether interest post-consumption is
      due primarily to food preference or acute satiety.

PMID- 29043251
TI  - NEAT HFpEF: Organic nitrates fail to deliver.

PMID- 29043249
TI  - Interactions between Bacteria and Bile Salts in the Gastrointestinal and
      Hepatobiliary Tracts.
AB  - Bile salts and bacteria have intricate relationships. The composition of the
      intestinal pool of bile salts is shaped by bacterial metabolism. In turn, bile
      salts play a role in intestinal homeostasis by controlling the size and the
      composition of the intestinal microbiota. As a consequence, alteration of the
      microbiome-bile salt homeostasis can play a role in hepatic and gastrointestinal
      pathological conditions. Intestinal bacteria use bile salts as environmental
      signals and in certain cases as nutrients and electron acceptors. However, bile
      salts are antibacterial compounds that disrupt bacterial membranes, denature
      proteins, chelate iron and calcium, cause oxidative damage to DNA, and control
      the expression of eukaryotic genes involved in host defense and immunity.
      Bacterial species adapted to the mammalian gut are able to endure the
      antibacterial activities of bile salts by multiple physiological adjustments that
      include remodeling of the cell envelope and activation of efflux systems and
      stress responses. Resistance to bile salts permits that certain bile-resistant
      pathogens can colonize the hepatobiliary tract, and an outstanding example is the
      chronic infection of the gall bladder by Salmonella enterica. A better
      understanding of the interactions between bacteria and bile salts may inspire
      novel therapeutic strategies for gastrointestinal and hepatobiliary diseases that
      involve microbiome alteration, as well as novel schemes against bacterial
      infections.

PMID- 29043252
TI  - Cardiovascular risk reduction in African Americans: Current concepts and
      controversies.

PMID- 29043253
TI  - Molecular mechanisms of cardiovascular benefits of exercise: Running for cover
      from heart disease.

PMID- 29043254
TI  - Alginate for cardiac regeneration: From seaweed to clinical trials.
AB  - Heart failure is a growing endemic in the aging Western population with a
      prevalence of over 20 million people worldwide1. Existing heart failure therapies
      are unable to reverse heart failure and do not address its fundamental cause, the
      loss of cardiomyocytes2. In order to induce myocardial regeneration for the
      myocardium and the heart valve, facilitate self-repair, improve tissue salvage,
      reduce or reverse the adverse-remodeling and ultimately achieve long-term
      functional stabilization and improvement in the heart function, novel strategies
      for therapeutic regeneration are being developed which are aiming to compensate
      for the insufficient and low intrinsic regenerative ability of the adult heart3.
      Similarly, valve replacement with mechanical or biological substitutes meets
      numerous hurdles. New approaches using multicellular approaches and new material
      are extensively studied. Most of those strategies depend on biomaterials that
      help to achieve functional integrated vasculogenesis and myogenesis in the
      heart/tissue. Especially for failed heart valve function a number of therapeutic
      approaches are common from corrective intervention to complete replacement4.
      However the complexity of the heart valve tissue and its high physical exposure
      has led to a variety of approaches, however therapeutic regeneration needs to be
      established. Beside other approaches alginate has been identified as one building
      block to achieve therapeutic regeneration. Alginate is a versatile and adaptable
      biomaterial that has found numerous biomedical applications which include wound
      healing, drug delivery and tissue engineering. Due to its biologically favorable
      properties including the ease of gelation and its biocompatibility, alginate
      based hydrogels have been considered a particularly attractive material for the
      application in cardiac regeneration and valve replacement techniques. Here, we
      review current applications of alginate in cardiac regeneration as well as
      perspectives for the alginate-dependent, cardiac regeneration strategies.

PMID- 29043255
TI  - A global perspective of lung transplantation: Part 1 - Recipient selection and
      choice of procedure.
AB  - Lung transplantation has grown considerably in recent years and its availability
      has spread to an expanding number of countries worldwide. Importantly, survival
      has also steadily improved, making this an increasingly viable procedure for
      patients with end-stage lung disease and limited life expectancy. In this first
      of a series of articles, recipient selection and type of transplant operation are
      reviewed. Pulmonary fibrotic disorders are now the most indication in the U.S.,
      followed by chronic obstructive pulmonary disease and cystic fibrosis. Transplant
      centers have liberalized criteria to include older and more critically ill
      candidates. A careful, systematic, multi-disciplinary selection process is
      critical in identifying potential barriers that may increase risk and optimize
      long-term outcomes.

PMID- 29043256
TI  - Maturation of pluripotent stem cell derived cardiomyocytes: The new challenge.
AB  - Stem cell therapy appears to be a promising area of research for cardiac
      regeneration following ischemic heart failure. However, in vitro differentiation
      of cardiomyocytes from pluripotent stem cells, or directly from somatic cells,
      leads to generation of "immature" cardiomyocytes that differ from their adult
      counterparts in various ways. This immaturity triggers some challenges for their
      potential clinical use, and multiple techniques reviewed here have been developed
      for in vitro maturation of those cells. Nevertheless, full maturity of
      cardiomyocytes remains elusive and will remain the main challenge for stem cell
      therapy in the near future.

PMID- 29043257
TI  - Iranian homograft tissue processing.
AB  - Tissue transplantation is a life-enhancing therapeutic modality for damaged or
      non-functioning tissues. In most cases, there is no alternative other than human
      tissue as replacement, and taking into account the ever-increasing demand for
      tissue grafts, it makes sense to set up an establishment in charge of human
      tissue procurement to meet local needs. A quality assurance system, clearly
      defined standards, and regular audits complement the infrastructure which make
      this activity feasible. The process of tissue procurement consists of donor
      identification, consent, tissue recovery, donor screening and testing, tissue
      processing, preservation, packaging, labeling, terminal sterilization, storage
      and distribution. The transplantation of homograft heart valves remains
      controversial, due to the availability of prosthetic and bioprosthetic
      alternatives. The limited durability of homografts has not yet outweighed the
      advantages which this graft offers. Adherence to regulations and regularly
      revised guidelines improve long-term efficacy and minimizes complications or
      malfunction. Furthermore, the lower price of homograft heart valves and the
      removal of the need for a lifetime of anticoagulation therapy are noteworthy
      advantages of this replacement. In our practice, the proportion of homograft
      heart valves meeting release criteria and successfully implanted grafts were 83%
      and 95%, respectively.

PMID- 29043259
TI  - Acute myocarditis and pulmonary edema due to scorpion sting.
AB  - Objective: To present a case of a serious manifestation of scorpion sting, which
      was not reported before in Qatar, review the literature, and compare with
      previously reported similar cases. Case presentation and intervention: A young
      male patient was admitted to CCU with a clinical picture of acute toxic
      myocarditis and cardiogenic shock with abnormal ECG and elevated cardiac markers
      after a scorpion sting to his right big toe. Thorough investigations, including
      echocardiography, cardiac MRI and right heart catheterization, supported the
      diagnosis. Coronary angiography was normal. Patient was managed conservatively
      with supportive measures, mechanical ventilation, IV fluids, inotropic agents,
      steroids, antibiotics and Prazocin. Over 9 days of hospital course, patient
      gradually improved, was successfully extubated, and was discharged in a stable
      condition. Conclusion: Toxic myocarditis (with myocardial damage), pulmonary
      edema and cardiogenic shock are reported manifestations of scorpion venom
      intoxication.

PMID- 29043258
TI  - Insights from the International Registry of Acute Aortic Dissection.

PMID- 29043261
TI  - African leaders take action on RHD: The 4th All-Africa Workshop on Acute
      Rheumatic Fever and Rheumatic Heart Disease & African Union RHD Communique.

PMID- 29043260
TI  - Muscle contraction: Sliding filament history, sarcomere dynamics and the two
      Huxleys.
AB  - Despite having all the evidence needed to come to the right conclusions in the
      middle of the 1800s, it was not until the 1950s that it was realised by two
      unrelated Huxleys and their collaborators that striated muscle sarcomeres contain
      overlapping sets of filaments which do not change much in length and which slide
      past each other when the muscle sarcomere shortens. It then took quite a while to
      convince others that this was the case, but now the idea of sliding filaments is
      fundamental to our understanding of how any muscle works. Here a brief overview
      of the history of the discovery of sliding filaments and the factors that were
      missed in the 1800s is followed by an analysis of the more recent experiments
      which have added to the conviction that all muscles operate on the same guiding
      principles; two sets of sliding filaments, independent force generators and a
      mechanism of protein rowing that makes the filaments slide.

PMID- 29043262
TI  - ASGR1 - a new target for lowering non-HDL cholesterol.
AB  - Non-HDL cholesterol (non-HDL-C) has been introduced as an alternative
      cardiovascular (CV) risk marker and a secondary therapeutic target in patients
      with combined hyperlipidemia, diabetes mellitus, metabolic syndrome, or chronic
      kidney disease. An important genetic study on the Icelandic population has
      recently identified a strong link between a new gene - ASGR1 (for
      asialoglycoprotein receptor) - mutation, plasma non-HDL-C levels, and coronary
      heart disease (CHD). Heterozygous carriers of a rare noncoding 12-base-pair (bp)
      deletion (del12 deletion) in intron 4 of ASGR1 had a 13.6 mg/dl lower level of
      non-HDL-C and a 34% lower risk of CHD than non carriers. The cardioprotective
      effect of ASGR1 loss-of-function is surprisingly larger than predicted by its
      effect on the levels of non-HDL-C, which suggests that the atheroprotective
      effects of del12 mutation go beyond the lowering of serum cholesterol levels.
      This has shed some light on a new path - the sialylation pathway - possibly
      leading to a novel therapy that neutralize ASGR1 for heart disease prevention and
      treatment.

PMID- 29043263
TI  - CTS trials network: Rate control vs rhythm control for atrial fibrillation after
      cardiac surgery - Do bitter pills have blessed effects?
AB  - New onset AF is a very common sequel of cardiac surgery with an incidence
      reaching 50% in some studies. This post-operative complication leads to increased
      morbidity, hospital stay and, consequently, hospital costs1. Currently there is a
      great variability in the management of this condition. Despite efforts to produce
      best practice guidelines2, what best to do for a patient who develops AF post
      operatively remains a question. In a systematic attempt to find an answer to this
      question, the Cardiothoracic Trials Network have recently published the results
      of their trial "Rate Control Versus Rhythm Control for Atrial Fibrillation After
      Cardiac Surgery"3 (clinicaltrials.gov number: NCT02132767).

PMID- 29043265
TI  - Percutaneous mitral valve repair: The MitraClip device.
AB  - Chronic mitral regurgitation (MR) is the most common cardiac valvular disease
      with more than 4 million people in the United States alone suffering from
      moderate or severe MR. Left untreated, chronic MR results in serious
      consequences. Surgical correction with mitral valve repair or replacement remains
      the mainstay of therapy for MR. Nevertheless, a large proportion of patients may
      not be offered treatment due to concerns over surgical risk. This unmet
      therapeutic need for a less invasive approach led to a marked explosion in the
      development of a variety of transcatheter approaches to treat mitral
      regurgitation in the past decade. The majority of these devices are based on
      principles learned from surgical mitral valve repair techniques. Inspired by the
      Alfieri surgical technique, the MitraClip edge-to-edge repair system is the most
      advanced technique with the highest safety and efficacy to date. In this review,
      we discuss the current status of the MitraClip repair system in the treatment of
      mitral regurgitation.

PMID- 29043264
TI  - Advanced fluorescence microscopy techniques for the life sciences.
AB  - The development of super-resolved fluorescence microscopy, for which the Nobel
      Prize was awarded in 2014, has been a topic of interest to physicists and
      biologists alike. It is inevitable that numerous questions in biomedical research
      cannot be answered by means other than direct observation. In this review,
      advances to fluorescence microscopy are covered in a widely accessible fashion to
      facilitate its use in decisions related to its acquisition and utilization in
      biomedical research.

PMID- 29043267
TI  - Juxtaposition of the atrial appendages: A nidus for thrombus in atriopulmonary
      Fontan?
AB  - Juxtaposition of atrial appendages is a rare cardiac congenital anomaly, usually
      associated with other cardiac malformations. Until now, it has not been linked to
      any significant clinical implications. We report cardiovascular magnetic
      resonance (CMR) findings of two adult patients who underwent atriopulmonary
      Fontan operation in the setting of left juxtaposition of the atrial appendages.
      The patients were in sinus rhythm at the time of the CMR study. Both patients had
      episodes of sustained atrial tachyarrhythmia requiring electrical cardioversion
      and were anticoagulated with warfarin with target INR 2-3. CMR images showed a
      thrombus located in the enlarged and juxtaposed right appendage in both patients.
      Blood flow frequently appears slow or sluggish in the dilated right atrium
      following atriopulmonary Fontan surgery. In addition, cine CMR suggested that
      blood flow reaches very low velocities in the massively dilated juxtaposed right
      atrial appendage cul-de-sac, thus potentially creating a substrate for clot
      formation. These findings propose that juxtaposed atrial appendages in
      atriopulmonary Fontan is an additional risk factor for clot formation,
      specifically in the dilated right atrial appendage on the left side juxtaposed
      with the left atrial appendage and that prophylactic anticoagulation is highly
      justified in these patients.

PMID- 29043266
TI  - Intracoronary near-infrared spectroscopy: an overview of the technology,
      histologic validation, and clinical applications.
AB  - Intracoronary near-infrared spectroscopy (NIRS) imaging, which is now clinically
      available in a combined NIRS and intravascular ultrasound catheter, is a novel
      catheter-based imaging modality capable of identifying lipid core plaque within
      the coronary arteries of living patients. The present manuscript provides an
      overview of intracoronary NIRS imaging with a focus on several concepts essential
      to individuals seeking to better understand this novel imaging modality. One of
      the major assets of NIRS is that it has been rigorously validated against the
      gold standard of histopathology and has been shown to accurately identify
      histologically-proven fibroatheroma. Clinical studies of NIRS have demonstrated
      its ability to accurately identify large lipid core plaques at culprit lesions
      across the spectrum of acute coronary syndromes. NIRS has also been shown to
      detect lesions at increased risk of causing peri-procedural myocardial infarction
      during PCI. With regards to predicting future risk, NIRS is seemingly capable of
      identifying vulnerable patients at increased risk of experiencing subsequent
      patient-level cardiovascular events. In addition to these clinical applications
      of NIRS, there are several large prospective observational studies underway to
      determine if NIRS imaging will be able to identify vulnerable plaques at
      increased risk of triggering site-specific future coronary events. These studies,
      once completed, are anticipated to provide valuable data regarding the ability of
      NIRS imaging to identify plaque vulnerability.

PMID- 29043268
TI  - Which way to grow? Force over time may be the heart's Dao de jing.

PMID- 29043269
TI  - PLATFORM at 90 days: Evaluating the clinical utility of FFRCT.
AB  - The advancement that took place in assessing fractional flow reserve (FFR) using
      various competing modalities led to numerous research trials to evaluate the
      clinical impact of each. Among those trials is the recently published PLATFORM
      study. The data was designed to compare two clinical scenarios; a combination of
      computed fluid dynamics with computed tomographic angiography (CTA-guided
      strategy) in non-obstructive coronary artery disease (CAD) on one arm, compared
      to the standard practice representing the other clinical arm. The study's results
      were evaluated for further evidence and clinical insights.

PMID- 29043270
TI  - FIRE AND ICE: The quest for the perfect modality in atrial fibrillation ablation.
AB  - Atrial fibrillation (AF) is the most common arrhythmia in clinical practice.
      Catheter ablation of atrial fibrillation plays an important role in the
      management of AF. Radiofrequency ablation is widely used in practice all over the
      world. Cryoablation has emerged as an alternative method for AF ablation. The
      FIRE and ICE trial was a non inferiority, multicentre, randomized trial that
      compared between the two modalities and proved cryoablation to be non inferior to
      radiofrequency in terms of efficacy and safety. However, the rate of AF
      recurrence was markedly high in both arms of the study.

PMID- 29043271
TI  - The role of mechanical circulatory support as destination therapy for ambulatory
      heart failure.
AB  - Continuous flow technology has dramatically improved patient survival during
      ventricular assist device (VAD) therapy in recent years. Health-related quality
      of life is improved by at least two years. Despite remarkable progress in this
      field, major adverse events during VAD support limit the effectiveness of this
      therapy and present major barriers to its extension to ambulatory advanced heart
      failure patients. The pace of progress will depend on improvements in both the
      adverse event profile and development of semi-quantitative methodology to
      calculate and display a composite of survival and health-related quality of life.

PMID- 29043272
TI  - Who gets a lung transplant? Assessing the psychosocial decision-making process
      for transplant listing.
AB  - In the United States, there is a significant shortage of available donor organs.
      This requires transplant professionals to hold simultaneous, yet divergent roles
      as (1) advocates for patients who are in need of a lifesaving transplant, and (2)
      responsible stewards in the allocation of scarce donor organs. In order to
      balance these roles, most transplant teams utilize a committee based decision
      making process to select suitable candidates for the transplant waiting list.
      These committees use medical and psychosocial criteria to guide their decision to
      list a patient. Transplant regulatory bodies have established medical standards
      for identifying appropriate medical candidates for transplantation. However,
      transplant regulatory bodies have not developed policies to standardize
      psychosocial criteria for listing patients. This affords transplant centers the
      autonomy to develop their own psychosocial criteria for determining which
      patients will be placed on the transplant waiting list. This lack of a
      standardized policy has resulted in inconsistent psychosocial practices amongst
      transplant centers nationwide. Since there has been no formal review of the
      inconsistency in psychosocial policy and practice, this paper seeks to explore
      the non-standardized psychosocial approach to organ transplant listing. The
      authors review factors that are relevant to the standardization of the
      psychosocial decision-making process, including shared decision-making, clinician
      judgment, bias in decision-making and moral distress in transplant staff. We
      conclude with a discussion about the impact of these issues on psychosocial
      practices in solid organ transplantation.

PMID- 29043273
TI  - Systems biology: An emerging strategy for discovering novel pathogenetic
      mechanisms that promote cardiovascular disease.
AB  - Reductionist theory proposes that analyzing complex systems according to their
      most fundamental components is required for problem resolution, and has served as
      the cornerstone of scientific methodology for more than four centuries. However,
      technological gains in the current scientific era now allow for the generation of
      large datasets that profile the proteomic, genomic, and metabolomic signatures of
      biological systems across a range of conditions. The accessibility of data on
      such a vast scale has, in turn, highlighted the limitations of reductionism,
      which is not conducive to analyses that consider multiple and contemporaneous
      interactions between intermediates within a pathway or across constructs. Systems
      biology has emerged as an alternative approach to analyze complex biological
      systems. This methodology is based on the generation of scale-free networks and,
      thus, provides a quantitative assessment of relationships between multiple
      intermediates, such as protein-protein interactions, within and between pathways
      of interest. In this way, systems biology is well positioned to identify novel
      targets implicated in the pathogenesis or treatment of diseases. In this review,
      the historical root and fundamental basis of systems biology, as well as the
      potential applications of this methodology are discussed with particular emphasis
      on integration of these concepts to further understanding of cardiovascular
      disorders such as coronary artery disease and pulmonary hypertension.

PMID- 29043274
TI  - 4D flow streamline characteristics of the great arteries twenty years after
      Lecompte and direct spiral arterial switch operation (DSASO) in simple TGA.
AB  - Transposition of the great arteries (TGA) is caused by discordance between the
      great arteries and the ventricles. If left untreated, this anomaly has a
      disastrous perspective. More recent surgical approach for correction includes the
      Lecompte technique in which the pulmonary bifurcation is transposed anterior to
      the aorta, which may be less physiologic. Although the early results are
      excellent, there is potential for future problems involving the great arteries
      and semilunar valves1. These potential problems necessitate the development of
      other improved surgical techniques2. Here we report an MRI 4D flow study related
      to a case of simple TGA whose primary surgical correction - direct spiral
      arterial switch operation (DSASO) - was performed twenty years ago in an attempt
      to restore physiologic arrangement among the great arteries and semilunar valves.

PMID- 29043275
TI  - Multivessel myocardial bridging in a patient with spiral hypertrophic
      cardiomyopathy.
AB  - Myocardial bridging is commonly observed in hypertrophic cardiomyopathy, usually
      confined to the left anterior descending (LAD), and correlates to the
      hypertrophic septum. We present a patient with unique spiral hypertrophic
      cardiomyopathy (HCM) and compression of all three coronary arteries corresponding
      to this hypertrophy pattern.

PMID- 29043278
TI  - Understanding the Contextual Factors Affecting Women's Health in Sistan and
      Baluchestan Province in Iran: A Qualitative Study.
AB  - BACKGROUND: Contextual factors impact health the same way social and cultural
      conditions do. Women's health, with its varying dimensions, is also under the
      influence of biological, societal, and cultural contexts. This typical condition
      has been developed along the continuum of their life cycle, bearing close
      correlation with their lif style. Therefore, identifying those marices within
      which women's health behaviors are formed is important.This study aims at
      exploring the contextual factors affecting women's health in Sistan and
      Baluchestan in Iran. METHODS: This study was carried out using a qualitative
      method, on a content analysis approach. Participants were 20 middle-aged women
      from Zahedan who entered the study with purposive sampling method. The method of
      collecting data was face-to- face and through conducting semi-structured
      interviews. After data collection, all interviews were transcribed, andreviewed,
      from which categories were extracted. The semantic similarities were revised and
      subcategories were identified, and then the related subcategories were arranged
      under one category. RESULTS: Two main categories of "features of context-based
      structure" and "changes in the cultural context" prove to be the basis for health
      behaviors in women. As for the category of "characteristics of context-based
      structure", individual, familial and environmental characteristics were
      identified, and regarding the category of "changes in the cultural context", the
      context-based cultural features were identified. CONCLUSION: The findings of the
      study suggest that effective contextual factors influencing women's living
      conditions had a decisive role in their health behaviors. In fact, the context-
      based structure in association with the cultural changes that have occurred in
      the beliefs of men and women, have had a decisive role in the women's health
      behaviors.

PMID- 29043277
TI  - The Effect of Telephone Counseling and Education on Breast Cancer Screening in
      Family Caregivers of Breast Cancer Patients.
AB  - BACKGROUND: Breast cancer is the most common form of malignancy among females.
      Family history is a key risk factor for breast cancer. Breast cancer screening
      practices are vital in patients with family history of breast cancer. Telephone
      counseling and education may be appropriate for improved breast cancer screening.
      This study was done to determine family caregiver patients' knowledge of risk
      factors for breast cancer and practice of breast cancer screening and also to
      assess the effect of telephone counseling and education on mammography screening.
      METHODS: This study was a community-based trial. The participants of the study
      were 90 caregivers who were randomly divided into an experimental group,
      telephone counseling and education, and a control group. The intervention group
      received counseling and education phone calls. A three-section questionnaire was
      responded and filled out through telephone interviews with the participants. The
      collected data were analyzed with SPSS18, using descriptive and inferential
      statistics. RESULTS: The results showed that 88.9% of the participants did not
      know when to do breast self-exam (BSE). Mammography was performed by the
      participants before and after the telephone counseling in intervention group
      (P<0.00), which were 13.3% and 77.8% respectively). Moreover, the major cause of
      failure to participate in mammography was lack of enough knowledge in 73.3% of
      the participants. CONCLUSION: This study concluded that knowledge and practice on
      breast cancer screening in family caregiver of breast cancer patients was low.
      Telephone counseling and educating may provide a suitable technique for earlier
      detection of breast cancer in family caregivers of breast cancer patients and it
      can influence the decision making regarding mammography screening among 40-year
      old or older women. Trial Registration Number: 2017052316870N3.

PMID- 29043276
TI  - Knitting for heart valve tissue engineering.
AB  - Knitting is a versatile technology which offers a large portfolio of products and
      solutions of interest in heart valve (HV) tissue engineering (TE). One of the
      main advantages of knitting is its ability to construct complex shapes and
      structures by precisely assembling the yarns in the desired position. With this
      in mind, knitting could be employed to construct a HV scaffold that closely
      resembles the authentic valve. This has the potential to reproduce the
      anisotropic structure that is characteristic of the heart valve with the yarns,
      in particular the 3-layered architecture of the leaflets. These yarns can provide
      oriented growth of cells lengthwise and consequently enable the deposition of
      extracellular matrix (ECM) proteins in an oriented manner. This technique,
      therefore, has a potential to provide a functional knitted scaffold, but to
      achieve that textile engineers need to gain a basic understanding of structural
      and mechanical aspects of the heart valve and in addition, tissue engineers must
      acquire the knowledge of tools and capacities that are essential in knitting
      technology. The aim of this review is to provide a platform to consolidate these
      two fields as well as to enable an efficient communication and cooperation among
      these two research areas.

PMID- 29043279
TI  - The Effect of Emotional Focused Intervention on Spousal Emotional Abuse and
      Marital Satisfaction among Elderly Married Couples: A Randomized Controlled
      Trial.
AB  - BACKGROUND: This study examined the impacts of an Emotional Focused Intervention
      on emotional abuse behaviors and marital satisfaction among the elderly married
      couples. METHODS: This randomized controlled trial study was carried out in
      Shiraz-Iran, during September 2013-2014. The elderly couples were invited to join
      an emotional focused intervention, following the advertisement and announcement
      on bulletin boards in the elderly day clinic centers and all governmental primary
      health care centers. Then, 57 couples (114 participants) who were eligible for
      study were assigned in two groups by block randomization (29 in the experimental
      and 28 in the control group(.The couples in the experimental group received
      intervention twice a week for four weeks. Each session lasted 90 minutes. The
      control group didn't receive any intervention and the subjects were put in the
      waiting list. The outcome measures were evaluated by Multidimensional Measure of
      Emotional Abuse Questionnaire (MMEAQ) and Marital Satisfaction Questionnaire for
      Older People (MSQFOP). Repeated measurement ANOVA was used to detect any
      significant changes between groups in their mean scores of emotional abuse
      behaviors and marital satisfaction from pre- to post-test, and 3 months after the
      intervention. Analysis of data was performed using SPSS, version 19, and P<=0.05
      was measured as significant. RESULTS: The mean duration of marriage was 39.56+/
      9.64 years. In the experimental group, the abusive behaviors decreased
      significantly (P<0.001) at times 2 and 3 compared with time 1, and marital
      satisfaction improved significantly only at time 3 (P<0.001). These differences
      were not significant in the control group. CONCLUSION: Emotion-focused couple
      based interventions are helpful in reducing the spousal emotional abuse and
      improving marital satisfaction in among the elderly couples. Trial Registration
      Number: 2013111715426N1.

PMID- 29043280
TI  - Prediction of Adequate Prenatal Care Utilization Based on the Extended Parallel
      Process Model.
AB  - BACKGROUND: Pregnancy complications are one of the major public health concerns.
      One of the main causes of preventable complications is the absence of or
      inadequate provision of prenatal care. The present study was conducted to
      investigate whether Extended Parallel Process Model's constructs can predict the
      utilization of prenatal care services. METHODS: The present longitudinal
      prospective study was conducted on 192 pregnant women selected through the multi
      stage sampling of health facilities in Qeshm, Hormozgan province, from April to
      June 2015. Participants were followed up from the first half of pregnancy until
      their childbirth to assess adequate or inadequate/non-utilization of prenatal
      care services. Data were collected using the structured Risk Behavior Diagnosis
      Scale. The analysis of the data was carried out in SPSS-22 using one-way ANOVA,
      linear regression and logistic regression analysis. The level of significance was
      set at 0.05. RESULTS: Totally, 178 pregnant women with a mean age of 25.31+/-5.42
      completed the study. Perceived self-efficacy (OR=25.23; P<0.001) and perceived
      susceptibility (OR=0.048; P<0.001) were two predictors of the intention to
      utilize prenatal care. Husband's occupation in the labor market (OR=0.43;
      P=0.02), unwanted pregnancy (OR=0.352; P<0.001), and the need to care for the
      minors or elderly at home (OR=0.35; P=0.045) were associated with lower odds of
      receiving prenatal care. CONCLUSION: The model showed that when perceived
      efficacy of the prenatal care services overcame the perceived threat, the
      likelihood of prenatal care usage will increase. This study identified some
      modifiable factors associated with prenatal care usage by women, providing key
      targets for appropriate clinical interventions.

PMID- 29043282
TI  - The Effect of Aromatherapy Treatment on Fatigue and Relaxation for Mothers during
      the Early Puerperal Period in Japan: A Pilot Study.
AB  - BACKGROUND: Early in the postpartum period, mothers are often nervous and tired
      from the delivery, breast-feeding and caring for a new-born. The aim of this
      study was to evaluate the process and outcome of using aromatherapy treatments to
      increase relaxation and decrease fatigue for mothers during the first to the
      seventh day of the postpartum period. METHODS: This non-randomized controlled
      study with a quasi-experimental one-group pretest-posttest design was used to
      evaluate scores in relaxation and fatigue before and after the intervention.
      Aromatherapy hand treatments were performed on a purposive sample of 34
      postpartum mothers in Tokyo, Japan, from May to July 2016. The single treatment
      included a choice of one of five essential aroma oils through hand and forearm
      massage. Relaxation and fatigue were measured by self-administered valid and
      reliable questionnaires. Wilcoxon signed-rank test was conducted to analyze the
      data before and after the intervention. The software programs SPSS, v. 23.0
      (SPSS, Tokyo), was used to analyze the data, with the significance level set at
      5%. RESULTS: Valid responses were obtained from 29 participants. A comparison of
      the scores before and after aroma treatment intervention indicated that the
      participants' relaxation scores increased significantly (P<0.001) and fatigue
      scores were significantly reduced (P<0.001). The majority of participants (77.8%)
      were satisfied with the treatment. CONCLUSION: The aroma treatments significantly
      improved relaxation and reduced fatigue for mothers in the early puerperal period
      and were well received. Therefore, a larger study using a pretest-posttest random
      control trial is recommended.

PMID- 29043281
TI  - Predictors of Post-Traumatic Stress Disorder among Victims of Serious Motor
      Vehicle Accidents.
AB  - BACKGROUND: Compelling evidence has shown that motor vehicle accidents have an
      enormous impact on mental health. Post-traumatic Stress Disorder (PTSD) is one of
      the most common psychological consequences in adult survivors of accidents, so it
      is important to understand the prevalence and predictors of this issue since
      delay causes damage to crucial daily functioning. This study aimed at
      investigating the prevalence and predictors of PTSD after motor vehicle accident.
      METHODS: This cross-sectional study was conducted on 528 injured patients six
      weeks to six months after motor vehicle accident in Imam Reza Clinic of Poursina
      hospital, Rasht in 2015. Data collection tools were three questionnaires
      including post-traumatic stress-self report (PSS), Beck Depression Inventory (BDI
      II), and the Numeric Rating Scale (NRS) for pain. The data were analyzed in SPSS
      (Version 19) using Chi-square, Fischer's exact test and multivariate logistic
      regression. Significance level was considered P<=0.05. RESULTS: The prevalence of
      PTSD and depression was 30.49% and 19.89% in participants, respectively. Chi
      square test indicated a significant relationship among age (P=0.02), sex
      (P<0.001), education level (P<0.001), work status (P<0.001) and PTSD.
      Participants who reported pain (P<0.001) and depression (P<0.001) were more
      likely to have high score of PTSD than the others. Multivariate logistic
      regression showed this significance in sex, depression, age, educational status
      and pain, as constant risk factors in developing PTSD after accident. CONCLUSION:
      This study suggests that primary care setting should be readily prompted for
      diagnosis of these disorders in non-treatment seeking individuals in the
      community.

PMID- 29043283
TI  - Barriers to Pap Smear Test for the Second Time in Women Referring to Health Care
      Centers in the South of Tehran: A Qualitative Approach.
AB  - BACKGROUND: Cervical cancer is a preventable disease with a regular screening
      program. Many studies have reported a large number of barriers that women had for
      the first time, but this study decided to find other barriers for the second time
      pap smear. METHODS: In this qualitative research, data were gathered through in
      depth interviews and expressed through conventional content analysis in the form
      of constant comparison. The participants were 15 women with family profile at 30
      health care centers who lived in the south of Tehran and had done Pap smear for
      one time but didn't do it for the second time. RESULTS: Three main themes emerged
      from the analysis of the interviews: negative experiences of the first Pap test
      were as follows: results of the first time test, readiness for performing the
      test, getting the test itself, and the site of the first Pap test. Personal
      barriers to getting the second Pap test were: inattention to time, physical
      barriers to the second Pap test, and inhibitory beliefs. Perceived social
      barriers to getting the second Pap test with two sub-themes included social
      supports and abstract norms. CONCLUSION: This study provided other barriers about
      Pap smear including lack of the spouse's support, the role of health care
      providers and physicians in screening program for early diagnosis in women.

PMID- 29043284
TI  - Exploring the Position of Community-Based Nursing in Iran: A Qualitative Study.
AB  - BACKGROUND: Community-based nursing focuses on providing health services to
      families and communities in the second and third levels of prevention and this
      can improve the individuals, families and communities' quality of life, and
      reduce the healthcare costs. The aim of this study was to explore the status of
      community-based nursing in Iran. METHODS: This qualitative study was conducted
      from March to November 2015, in Tehran, Iran, using the content analysis
      approach. The study setting consisted of Iran and Tehran Faculties of Nursing and
      Midwifery, Tehran, Iran. The purposive sampling method was used. Twenty faculty
      members and Master's and PhD students were interviewed by using the face-to-face
      semi-structured interview method. Moreover, two focus groups were conducted for
      complementing and enriching the study data. The data were analyzed using the
      Graneheim and Lundman's approach to content analysis. The trustworthiness of the
      study findings was maintained by employing the Lincoln and Guba's criteria of
      credibility, dependability, and confirmability. RESULTS: In total, 580 codes were
      generated and categorized into three main categories of conventional services,
      the necessity for creating infrastructures, and multidimensional outcomes of
      community-based nursing. CONCLUSION: Introducing community-based nursing into
      nursing education curricula and creating ample job opportunities for community
      based nurses seem clearly essential.

PMID- 29043285
TI  - The Relationship between Health Locus of Control and Health Behaviors in
      Emergency Medicine Personnel.
AB  - BACKGROUND: Health locus of control defined as individual beliefs based on past
      experiences in health issues and having external or internal control over them,
      could affect health. Health locus of control plays a role in health behaviors. We
      aimed to investigate the relationship between health locus of control and health
      behavior in emergency medical personnel in Ahvaz during 2016. METHODS: This is a
      cross-sectional descriptive study, which began in August 2016 for a period of six
      months on 215 emergency medical personnel in Ahvaz who were selected randomly.
      The data were collected by a demographic questionnaire, Rotter's locus of control
      questionnaire, and health behavior questionnaire and analyzed using SPSS
      software, version 22. The correlation between variables was estimated by
      Pearson's correlation coefficient and independent t test. The level of
      significance for all statistical tests was set at 0.05. RESULTS: We found no
      significant relationship between health locus of control (external and internal)
      and health behavior (P>0.05).Health behaviors were very good in terms of personal
      health (86.5%), nutrition (53%), and sleep and rest (48.4%), and poor in terms of
      physical activity (52.6%) and stress management (79.5%). Furthermore, 79.5% of
      the emergency personnel, in general, had poor heath behaviors. CONCLUSION:
      Leaders and officials in the field of health must necessarily design programs in
      relation to health locus of control and the factors developing and affecting it
      as well as the role of health locus of control in doing correct behaviors.

PMID- 29043286
TI  - Perceived Social Support and Maternal Competence in Primipara Women during
      Pregnancy and After Childbirth.
AB  - BACKGROUND: Developing maternal competence in first time mothers has a
      significant impact on neonate's growth psychosocial development and neonates
      growth and psychological development. Social support can be an important element
      for becoming a new mother. We aimed to investigate how social support and
      maternal competence change during pregnancy and 4 months after it and examine the
      relationships among social support and maternal competence. METHODS: This
      longitudinal study was conducted on 100 first time mothers attending health
      centers in Alborz city, Alborz Province, between February 2015 and January 2016.
      Data were collected through perceived social support questionnaire that consisted
      of 12 questions and Parenting Sense of Competence Scale consisting of 17 items
      scored based on Likert's scale. The collected data were analyzed by SPSS
      software, version 16. Repeated-measure test and Pearson's correlation coefficient
      were used. P<0.05 was considered significant. RESULTS: Maternal competence
      significantly reduced during the study (P=0.008), while perceived social support
      did not show any significant reduction (P=0.286). A direct relationship was found
      between social support and maternal competent six weeks after childbirth (r=0.19,
      P=0.049), and also social support and maternal competence sixteen weeks after
      childbirth (r=0.23, P=0.01). CONCLUSION: Considering the reduction of maternal
      competency during the study, social support by healthcare providers may be
      helpful for the mothers' transition to motherhood, and midwives must design
      specific interventions to promote the sense of maternal competence and perceived
      social support in first time mothers.

PMID- 29043287
TI  - Improving the Search Strategy of Systematic Reviews and Meta-Analysis.

PMID- 29043288
TI  - The Authors' Reply.

PMID- 29043289
TI  - Restoration of Completely Transected Common Bile Duct Continuity Using Single
      Operator Cholangioscopy.
AB  - Common bile duct (CBD) injury, ranging from a partial tear to a complete
      transection, is a major surgical complication of cholecystectomy with significant
      morbidity and mortality. Proper management of these complex injuries depends on
      the type and extent of injury and time of recognition. Identifying and repairing
      injuries during cholecystectomy can prevent development of complications, but
      this only occurs in about one-third of cases. We report a novel technique to
      reconnect a transected CBD with assistance of single-operator cholangioscopy.

PMID- 29043290
TI  - Checkpoint Inhibitor-Induced Colitis: A New Type of Inflammatory Bowel Disease?
AB  - Checkpoint inhibitors are immune-stimulatory antibodies that have transformed the
      management and prognosis of individuals with metastatic melanoma and other
      cancers. Checkpoint inhibitor-induced colitis is an increasingly recognized
      immune-related adverse event that shares many of the same phenotypical,
      serological, and histological characteristics of both Crohn's disease and
      ulcerative colitis, suggesting that checkpoint inhibitor-induced colitis may
      represent a new inflammatory bowel disease phenotype. We report a 73-year-old man
      with metastatic melanoma who developed ipilimumab-induced colitis with subsequent
      transformation to Crohn?s colitis-like phenotype after the addition of
      pembrolizumab.

PMID- 29043291
TI  - Fibroblastic Polyps: A Novel Polyp Subtype in Cowden Syndrome.
AB  - Cowden syndrome (CS) represents one possible phenotype of the PTEN gene mutation,
      and it can cause hamartomas throughout the gastrointestinal tract, with a
      predisposition for malignancy. Fibroblastic polyps have not been associated with
      CS. A 45-year-old woman with CS presenting for colonoscopic surveillance was
      found to have multiple sessile polyps throughout the transverse, descending, and
      sigmoid colon, all 2-5 mm in diameter. Based on the morphologic features and the
      immunohistochemical profile, these lesions were classified as fibroblastic
      polyps. This polyp subtype is recognized as a benign process of the colonic
      mucosa but is a novel histologic observation in the setting of CS.

PMID- 29043292
TI  - Phyllodes tumors with and without fibroadenoma-like areas display distinct
      genomic features and may evolve through distinct pathways.
AB  - Breast fibroepithelial lesions (fibroadenomas and phyllodes tumors) are
      underpinned by recurrent MED12 exon 2 mutations, which are more common in
      fibroadenomas and benign phyllodes tumors. TERT promoter hotspot mutations have
      been documented in phyllodes tumors, and found to be more frequent in borderline
      and malignant lesions. Several lines of evidence suggest that a subset of
      phyllodes tumors might arise from fibroadenomas. Here we sought to investigate
      the genetic differences between phyllodes tumors with fibroadenoma-like areas vs.
      those without. We retrieved data for 16 borderline/ malignant phyllodes tumors,
      including seven phyllodes tumors with fibroadenoma-like areas and nine phyllodes
      tumors without fibroadenoma-like areas, which had been previously subjected to
      targeted capture massively parallel sequencing. Whilst MED12 exon 2 mutations
      were significantly more frequent in tumors with fibroadenoma-like areas (71 vs.
      11%), an enrichment in genetic alterations targeting bona fide cancer genes was
      found in those without fibroadenoma-like areas, in particular in EGFR mutations
      and amplifications (78 vs. 14%). No significant difference in the frequency of
      TERT genetic alterations was observed (71% in cases with fibroadenoma-like areas
      vs 56% in those without fibroadenoma-like areas). Our data suggest that the
      development of phyllodes tumors might follow two different evolutionary pathways:
      a MED12-mutant pathway that involves the progression from a fibroadenoma to a
      malignant phyllodes tumor; and a MED12-wild-type pathway, where malignant
      phyllodes tumors arise de novo through the acquisition of genetic alterations
      targeting cancer genes. Additional studies are warranted to confirm our
      observations and define whether the outcome differs between both pathways.

PMID- 29043293
TI  - Classical strong metal-support interactions between gold nanoparticles and
      titanium dioxide.
AB  - Supported metal catalysts play a central role in the modern chemical industry but
      often exhibit poor on-stream stability. The strong metal-support interaction
      (SMSI) offers a route to control the structural properties of supported metals
      and, hence, their reactivity and stability. Conventional wisdom holds that
      supported Au cannot manifest a classical SMSI, which is characterized by
      reversible metal encapsulation by the support upon high-temperature redox
      treatments. We demonstrate a classical SMSI for Au/TiO2, evidenced by suppression
      of CO adsorption, electron transfer from TiO2 to Au nanoparticles, and gold
      encapsulation by a TiO x overlayer following high-temperature reduction (reversed
      by subsequent oxidation), akin to that observed for titania-supported platinum
      group metals. In the SMSI state, Au/TiO2 exhibits markedly improved stability
      toward CO oxidation. The SMSI extends to Au supported over other reducible oxides
      (Fe3O4 and CeO2) and other group IB metals (Cu and Ag) over titania. This
      discovery highlights the general nature of the classical SMSI and unlocks the
      development of thermochemically stable IB metal catalysts.

PMID- 29043294
TI  - Integrating networks and comparative genomics reveals retroelement proliferation
      dynamics in hominid genomes.
AB  - Retroelements (REs) are mobile DNA sequences that multiply and spread throughout
      genomes by a copy-and-paste mechanism. These parasitic elements are active in
      diverse genomes, from yeast to humans, where they promote diversity, cause
      disease, and accelerate evolution. Because of their high copy number and sequence
      similarity, studying their activity and tracking their proliferation dynamics is
      a challenge. It is particularly difficult to pinpoint the few REs in a genome
      that are still active in the haystack of degenerate and suppressed elements. We
      develop a computational framework based on network theory that tracks the path of
      RE proliferation throughout evolution. We analyze SVA (SINE-VNTR-Alu), the
      youngest RE family in human genomes, to understand RE dynamics across hominids.
      Integrating comparative genomics and network tools enables us to track the course
      of SVA proliferation, identify yet unknown active communities, and detect
      tentative "master REs" that played key roles in SVA propagation, providing strong
      support for the fundamental "master gene" model of RE proliferation. The method
      is generic and thus can be applied to REs of any of the thousands of available
      genomes to identify active RE communities and master REs that were pivotal in the
      evolution of their host genomes.

PMID- 29043295
TI  - Three-dimensional supercritical resolved light-induced magnetic holography.
AB  - In the era of big data, there exists a growing gap between data generated and
      storage capacity using two-dimensional (2D) magnetic storage technologies (for
      example, hard disk drives), because they have reached their performance
      saturation. 3D volumetric all-optical magnetic holography is emerging rapidly as
      a promising road map to realizing high-density capacity for its fast
      magnetization control and subwavelength magnetization volume. However, most of
      the reported light-induced magnetization confronts the problems of impurely
      longitudinal magnetization, diffraction-limited spot, and uncontrollable
      magnetization reversal. To overcome these challenges, we propose a novel 3D light
      induced magnetic holography based on the conceptual supercritical design with
      multibeam combination in the 4pi microscopic system. We theoretically demonstrate
      a 3D deep super-resolved [Formula: see text] purely longitudinal magnetization
      spot by focusing six coherent circularly polarized beams with two opposing high
      numerical aperture objectives, which allows 3D magnetic holography with a
      volumetric storage density of up to 1872 terabit per cubic inches. The number and
      locations of the super-resolved magnetization spots are controllable, and thus,
      desired magnetization arrays in 3D volume can be produced with properly designed
      phase filters. Moreover, flexible magnetization reversals are also demonstrated
      in multifocal arrays by using different illuminations with opposite light
      helicity. In addition to data storage, this magnetic holography may find
      applications in information security, such as identity verification for a credit
      card with magnetic stripe.

PMID- 29043297
TI  - Clinical Efficacy of Alprostadil Combined with alpha-lipoic Acid in the Treatment
      of Elderly Patients with Diabetic Nephropathy.
AB  - OBJECTIVE: To evaluate the effect and toxicity of alprostadil combined with
      thioctic acid injection in the treatment of patients with diabetic nephropathy
      (DN). METHODS: Sixty two patients with DN were included in this study and
      randomly divided into control group (n=32) and experiment group (n=30). Patients
      in the control group were given alprostadil 20ug+NS 100ml ivgtt, qd and patients
      in the experiment group were given alprostadil 20ug+NS 100ml ivgtt combined with
      thioctic acid injection of 0.45g+100ml ivgtt, qd for 14 days. After treatment,
      the renal function and serum level of CRP, IL-6 and TNF-alpha were compared
      between the two groups. RESULTS: After two weeks of treatment, the serum level of
      CysC and UAER significant decreased for both control and experiment group with
      statistical difference of p<0.05. After treatment, the serum level of CysC were
      1.40 +/-0.46 mg/L and 1.02+/-0.33 for control and experiment group respectively
      (p<0.05). The post-treatment UAER in experiment group was significantly lower
      than those of control group with statistical difference (81.02+/-0.33 vs112.45+/
      20.32, p<0.05) ug/min. The serum level of CRP, IL-6 and TNF-alpha were
      significantly decreased after treatment for both control and experiment group
      (p<0.05). And the post-treatment serum CRP, IL-6 and TNF-alpha in experiment
      group were significantly lower than those of control group with statistical
      difference (p<0.05). No significant side effects were found for the two groupsin
      the course of treatment. CONCLUSION: Alprostadil combined with alpha-lipoic acid
      may improve renal function in patients with diabetic nephropathy by decreasing
      the levels of serum inflammatory factors.

PMID- 29043296
TI  - Lead halide perovskites: Crystal-liquid duality, phonon glass electron crystals,
      and large polaron formation.
AB  - Lead halide perovskites have been demonstrated as high performance materials in
      solar cells and light-emitting devices. These materials are characterized by
      coherent band transport expected from crystalline semiconductors, but dielectric
      responses and phonon dynamics typical of liquids. This "crystal-liquid" duality
      implies that lead halide perovskites belong to phonon glass electron crystals, a
      class of materials believed to make the most efficient thermoelectrics. We show
      that the crystal-liquid duality and the resulting dielectric response are
      responsible for large polaron formation and screening of charge carriers, leading
      to defect tolerance, moderate charge carrier mobility, and radiative
      recombination properties. Large polaron formation, along with the phonon glass
      character, may also explain the marked reduction in hot carrier cooling rates in
      these materials.

PMID- 29043298
TI  - Professional Burnout and Concurrent Health Complaints in Neonatal Nursing.
AB  - : The aim of this study was to analyze nurses' professional burnout and health
      complaints and the relationship between the two components. METHODS: The
      anonymous survey included 94 neonatal intensive care nurses from two centers of
      perinatology. The Maslach Burnout Inventory-Human Services Survey (MBI-HSS) was
      used to evaluate professional burnout; it consisted of 3 components, Emotional
      Exhaustion, Depersonalization, and Personal Accomplishments, with 22 items in
      total. Health complaints were evaluated by 21 items, where nurses were asked to
      report the occurrence of symptoms within the last year. Scale means were
      presented with standard deviations (SD). Inferential analysis was conducted with
      multivariate logistic regression, adjusting for age, residence, and work
      experience. RESULTS: The mean score of professional burnout on the Emotional
      Exhaustion subscale was 14.4 (SD=7.91), Depersonalization 3.8 (SD=4.75), and
      Personal Accomplishment 29.1 (SD=10.12). The health assessment revealed that
      sleeplessness, lack of rest, nervousness, and tiredness were the most common
      complaints. The regression analysis revealed that tiredness was independently
      associated with significantly increased odds of professional burnout (OR=4.1).
      CONCLUSIONS: In our study, more than half of the nurses in neonatal intensive
      care had moderate or high levels of emotional exhaustion, while levels of
      depersonalization were significantly lower. In contrast, the level of personal
      accomplishment was low in more than half of the nurses. The most common health
      complaints were sleep disturbances, nervousness, and tiredness. Tiredness was
      most strongly associated with professional burnout.

PMID- 29043300
TI  - Serum AFU, 5'-NT and AFP as Biomarkers for Primary Hepatocellular Carcinoma
      Diagnosis.
AB  - : To evaluate the clinical value of serum alpha-L-fucosidase (AFU), 5'
      nucleotidase (5'-NT) and alpha fetoprotein (AFP) as biomarkers for primary
      hepatocellular carcinoma (PHC) diagnosis. METHODS: Thirty six primary
      hepatocellular carcinoma (PHC) patients and 36 healthy controls were recruited in
      this study from February 2014 to January 2016 in the Second People's Hospital of
      Tianjin. The serum level of AFU, 5'-NT and AFP were examined and compared between
      the two groups. The diagnostic sensitivity, specificity area under the receiver
      operating characteristic (ROC) curve were calculated by STATA11.0 software.
      RESULTS: The serum level of AFU, 5'-NT, AFP were 30.87+/-10.43(U/L), 5.58+/
      3.89(U/L), 233.60+/-226.60 (MUg/L) respectively for primary hepatocellular
      carcinoma group and 19.96+/-6.73 (U/L), 1.87+/-0.84 (U/L), 16.64+/-14.17 (MUg/L)
      for healthy control groups. The serum level of AFU, 5'-NT and AFP in primary
      hepatocellular carcinoma group were significant higher than those of healthy
      control group (P<0.001). The diagnostic sensitivity and specificity were 0.78
      (95%CI:l0.61-0.90), 0.64 (95%CI:0.46-0.79) for serum AFU, 0.75(95%CI:0.58-0.88),
      0.72(95%CI:0.55- 0.86) for serum 5'-NT and 0.72 (95%CI:0.55-0.86), 0.92
      (95%CI:0.78-0.98) for serum AFP respectively. The AUC under the ROC curve were
      0.80 (0.69-0.90), 0.80 (0.69-0.91) and 0.87 (0.780-0.96) for serum AFU, 5'-NT and
      AFP respectively. Positive correlation between AFU and 5'-NT (rpearson=0.63,
      P<0.05), AFU and AFP (rpearson=0.49, P<0.05), 5'-NT and AFP(rpearson=0.44,
      P<0.05) were found in the primary hepatocellular carcinoma patients. CONCLUSION:
      Serum AFU, 5'-NT and AFP were higher in PHC patients than those of healthy
      controls. The difference between PHC patients and healthy controls made serum
      AFU, 5'-NT and AFP potential biomarker for PHC diagnosis.

PMID- 29043301
TI  - Complex multiblock bottle-brush architectures by RAFT polymerization.
AB  - The combination of the reversible addition fragmentation chain transfer (RAFT)
      polymerization R-group grafting from approach and RAFT one-pot acrylamide
      multiblock methodology is used to synthesise complex bottle-brush architectures.
      This is demonstrated for block copolymer grafted side chains and the insertion of
      ungrafted blocks into the backbone to yield multi-segmented bottle-brushes.

PMID- 29043299
TI  - CK20 mRNA Expression in Serum as a Biomarker for Colorectal Cancer Diagnosis: A
      Meta-analysis.
AB  - The aim of this study was to evaluate the diagnostic value of serumCK20 mRNA as a
      biomarker for colorectal cancer diagnosis by meta-analysis. Clinical studies
      related to serum CK20 mRNA expression for colorectal cancer diagnosis were
      searched in the databases of Pubmed, Cochrane Library, Embase, ISI Web of
      Knowledge, CNKI and Wanfang. The number of true positive (tp), false positive
      (fp), false negative (fn) and true negative (tn) of the original included
      publications were extracted by two reviewers independently. The diagnostic
      sensitivity, specificity, positive likely hood ratio (+LR), negative likelyhood
      ratio (-LR), diagnostic odds ratio (DOR) and area under the symmetric ROC curve
      (AUC) were pooled by random or fixed effect method according to the statistical
      heterogeneity among the studies. After screening the databases, nineteen
      publications met the inclusion criteria and were finally included in this meta
      analysis. The diagnostic sensitivity and specificity were pooled by random effect
      model(I2>50%). The pooled diagnostic sensitivity and specificity of CK20 mRNA in
      serum as biomarker for colorectal cancer were 0.49 (95% CI:0.46 to 0.51) and 0.94
      (95%CI:0.92-0.96) respectively. The pooled +LR and -LR were 10.90 (95%CI:5.78 to
      20.55) and 0.51 (95%CI:0.45 to 0.57) respectively by random-effect method. The
      pooled DOR was 22.31 with the 95% CI of 11.65 to 42.71. The pooled area under the
      ROC curve (AUC) was 0.72for CK20 mRNA in serum as a biomarker for colorectal
      cancer diagnosis. Conclusion Serum CK20 mRNA expression was significantly
      elevated in colorectal cancer patients which could be a promising serum biomarker
      for colorectal cancer diagnosis with high specificity.

PMID- 29043302
TI  - Foamed silicon particles as a high capacity anode material for lithium-ion
      batteries.
AB  - We report foamed Si particles as a high-performance lithium storage material
      prepared by a milling-assisted alkaline etching process. The resulting foamed Si
      electrode showed excellent cycling performance of over 300 cycles with an initial
      discharge capacity of about 2750 mA h g-1.

PMID- 29043303
TI  - Protein dynamics promote hydride tunnelling in substrate oxidation by aryl
      alcohol oxidase.
AB  - The temperature dependence of hydride transfer from the substrate to the N5 of
      the FAD cofactor during the reductive half-reaction of Pleurotus eryngii aryl
      alcohol oxidase (AAO) is assessed here. Kinetic isotope effects on both the pre
      steady state reduction of the enzyme and its steady-state kinetics, with
      differently deuterated substrates, suggest an environmentally-coupled quantum
      mechanical tunnelling process. Moreover, those kinetic data, along with the
      crystallographic structure of the enzyme in complex with a substrate analogue,
      indicate that AAO shows a pre-organized active site that would only require the
      approaching of the hydride donor and acceptor for the tunnelled transfer to take
      place. Modification of the enzyme's active-site architecture by replacement of
      Tyr92, a residue establishing hydrophobic interactions with the substrate
      analogue in the crystal structure, in the Y92F, Y92L and Y92W variants resulted
      in different temperature dependence patterns that indicated a role of this
      residue in modulating the transfer reaction.

PMID- 29043304
TI  - A single stranded fluorescent peptide probe for targeting collagen in connective
      tissues.
AB  - We herein report the construction of a novel single stranded fluorescent collagen
      mimetic peptide by introducing a bulky FAM dye in the central region rather than
      the N terminus. Without the need for any prior thermal or ultraviolet treatment,
      the peptide probe can be conveniently applied to specifically target collagen in
      connective tissues for fluorescence imaging.

PMID- 29043305
TI  - Unprecedented rearrangement of diketopyrrolopyrroles leads to structurally unique
      chromophores.
AB  - Diketopyrrolopyrroles possessing thienyl, furyl and benzofuryl substituents
      undergo unprecedented skeletal rearrangement in the presence of trimethylsilyl
      bromide resulting in the formation of thieno[2,3-f]isoindole-5,8-diones and
      furo[2,3-f]isoindole-5,8-diones. These relatively small dyes possess favorable
      photophysical properties with the emission maxima within the range of 573-624 nm,
      large fluorescence quantum yields, moderate sensitivity of emission to solvent
      polarity and a HOMO-LUMO gap of ca. 1.8 eV.

PMID- 29043306
TI  - Palladium-catalyzed denitrogenative functionalizations of benzotriazoles with
      alkenes and 1,3-dienes.
AB  - Pd-Catalyzed denitrogenative functionalizations of benzotriazoles with alkenes
      and 1,3-dienes have been developed, which enable the rapid access of diverse
      ortho-amino styrenes and 2-vinylindolines, respectively. This study shows the
      great potential of benzotriazoles as a [1C]-synthon in cross-coupling reactions
      and an aza-[3C]-synthon in cycloaddition reactions.

PMID- 29043307
TI  - Insight into the multiple quasi-molecular states in ethylenediamine reduced
      graphene nanodots.
AB  - Recently, graphene nanodots (GNDs) have been frequently considered as inherently
      heterogeneous systems, leading to multicolor emission under a changeable
      excitation wavelength. However, an accurate picture of the GNDs and an exhaustive
      structure-property correlation are still lacking. Using a two dimensional
      photoluminescence excitation (2D-PLE) map, molecular orbital calculation,
      reduction level dependent PL analysis, absorption spectroscopy and time-resolved
      PL spectroscopy, three cases of quasi-molecular PL are determined in
      ethylenediamine (EDA) reduced GNDs, including the C[double bond, length as m
      dash]O related electronic state, graphenol related electronic state and large pi
      conjugated domains. The graphenol structure is expected to be created via
      nucleophilic addition-elimination reactions between epoxide groups and EDA,
      contributing most to the blue-shifted and enhanced PL of GNDs. The multiple quasi
      molecular PL provides deeper insights into the commonly called "excitation
      wavelength dependent PL". An effort is made to utilize the heterogeneous
      photoluminescence through phosphor-based light-emitting diodes employing reduced
      GNDs as a phosphor, which are capable of converting blue light into white light.

PMID- 29043308
TI  - Geometrical flexibility of platinum nanoclusters: impacts on catalytic
      decomposition of ethylene glycol.
AB  - Catalytic decomposition of ethylene glycol on the Pt13 cluster was studied as a
      model system for hydrogen production from a lignocellulosic material. Ethylene
      glycol was chosen as a starting material because of two reasons, it is the
      smallest oxygenate with a 1 : 1 carbon to oxygen ratio and it contains the C-H, O
      H, C-C, and C-O bonds also present in biomass. Density functional theory
      calculations were employed for predictions of reaction pathways for C-H, O-H, C-C
      and C-O cleavages, and Bronsted-Evans-Polanyi relationships were established
      between the final state and the transition state for all mechanisms. The results
      show that Pt13 catalyzes the cleavage reactions of ethylene glycol more
      favourably than a Pt surface. The flexibility of Pt13 clusters during the
      reactions is the key factor in reducing the activation barrier. Overall, the
      results demonstrate that ethylene glycol and thus biomass can be efficiently
      converted into hydrogen using platinum nanoclusters as catalysts.

PMID- 29043309
TI  - Cyanamide as a prebiotic phosphate activating agent - catalysis by simple 2
      oxoacid salts.
AB  - Cyanamide is a prebiotically plausible compound that has previously been invoked
      as a phosphate activating agent. However, its reactions with phosphate monoesters
      are very slow and tend to be low yielding. We now report a fast and efficient
      phosphate activation reaction using cyanamide in the presence of glyoxylate or
      pyruvate. These simple 2-oxoacid salts are shown to function as catalysts and in
      an optimised system, adenosine-3'-phosphate was converted to adenosine-2',3'
      cyclic phosphate in 95% yield.

PMID- 29043310
TI  - LK peptide side chain dynamics at interfaces are independent of secondary
      structure.
AB  - Protein side chain dynamics are critical for specific protein binding to surfaces
      and protein-driven surface manipulation. At the same time, it is highly
      challenging to probe side chain motions specifically at interfaces. One important
      open question is the degree to which the motions of side chains are dictated by
      local protein folding or by interactions with the surface. Here, we present a
      real-time measurement of the orientational dynamics of leucine side chains within
      leucine-lysine (LK) model peptides at the water-air interface, with three
      representative peptide folds: alpha-helix, 310-helix and beta-strand. The
      results, modeled and supported by molecular dynamics simulations, show that the
      different peptide folds exhibit remarkably similar sub-picosecond orientational
      side chain dynamics at the air/water interface. This demonstrates that the side
      chain motional dynamics is decoupled from the local secondary structure.

PMID- 29043311
TI  - Strain induced atomic structure at the Ir-doped LaAlO3/SrTiO3 interface.
AB  - The structure of Ir-doped LaAlO3/SrTiO3(001) interfaces was investigated on the
      atomic scale using probe-corrected transmission electron microscopy in high-angle
      annular dark-field scanning mode (HAADF-STEM) and electron energy loss
      spectroscopy (EELS), combined with first-principles calculations. We report the
      evolution of the strain state experimentally measured in a 5 unit-cell thick
      LaAlO3 film as a function of the Ir concentration in the topmost SrTiO3 layer. It
      is shown that the LaAlO3 layers remain fully elastically strained up to 3% of Ir
      doping, whereas a higher doping level seems to promote strain relaxation through
      enhanced cationic interdiffusion. The observed differences between the energy
      loss near edge structure (ELNES) of Ti-L2,3 and O-K edges at non-doped and Ir
      doped interfaces are consistent with the location of the Ir dopants at the
      interface, up to 3% of Ir doping. These findings, supported by the results of
      density functional theory (DFT) calculations, provide strong evidence that the
      effect of dopant concentrations on the properties of this kind of interface
      should not be analyzed without obtaining essential information from the fine
      structural and chemical analysis of the grown structures.

PMID- 29043312
TI  - Investigation of the surface plasmon polariton and electrochemical properties of
      covalent and non-covalent functionalized reduced graphene oxide.
AB  - The surface electronic properties of graphene oxide (GO) were modified through
      reduction and functionalization. Non-covalent functionalization was found to be
      superior compared to covalent functionalization due to the formation of few-layer
      graphene with a low defect content and average crystalline length. Because of the
      restoration of sp2 hybridization, non-covalently functionalized reduced graphene
      oxide (rGO) showed a better plasmonic response compared to GO, rGO and covalently
      functionalized rGO. Due to the available pi electrons from the sp2 network of
      graphene as well as surface functionality, non-covalent functionalized rGO
      exhibited elevated donor density. Furthermore, due to the synergistic effect of
      surface electronic properties as well as adsorption and recombination at the
      barrier, superior charge transfer was achieved at the electrode-electrolyte
      interface for non-covalent functionalized rGO.

PMID- 29043313
TI  - Proton mobility in aqueous systems: combining ab initio accuracy with millisecond
      timescales.
AB  - We present a multiscale simulation of proton transport in liquid water, combining
      ab initio molecular dynamics simulations with force-field ensemble averaging and
      kinetic Monte-Carlo simulations. This unique Ansatz allows for ab initio accuracy
      incorporating the femtosecond dielectric relaxation dynamics of the aqueous
      hydrogen bonding network, and bridges the time-scale gap towards the explicit
      simulation of millisecond diffusion dynamics.

PMID- 29043314
TI  - N-Functionalized MXenes: ultrahigh carrier mobility and multifunctional
      properties.
AB  - Two dimensional (2D) nanomaterials have demonstrated huge potential in wide
      applications from nanodevices to energy harvesting/storage. In this work, we
      propose a new class of 2D monolayers, nitrogen-functionalized MXenes (Nb2CN2 and
      Ta2CN2), based on density-functional theory (DFT). We find that these monolayers
      are direct semiconductors with near linear energy dispersions at the Gamma point.
      M2CN2 monolayers have significant small effective mass and show an ultra-high
      mobility of up to 106 cm2 V-1 s-1. We show that the electronic structures of the
      M2CN2 monolayers can be easily controlled by biaxial and uniaxial strains.
      Importantly, the carrier mobility and direct band gap can be dramatically
      increased within a certain range of strain. A direct-indirect band gap transition
      can be triggered and the band gap can be tuned under strain. The tunable
      electronic properties are attributed to the structural changes and charge
      redistribution under stain. Our findings demonstrate that N-functionalized MXenes
      are promising materials for nanodevices with high speed and low power.

PMID- 29043315
TI  - Quantification of cation-anion interactions in crystalline monopotassium and
      monosodium glutamate salts.
AB  - Crystalline salt compounds composed of metal cations and organic anions are
      becoming increasingly popular in a number of fields, including the pharmaceutical
      and food industries, where such formulations can lead to increased product
      solubility. The origins of these effects are often in the interactions between
      the individual components in the crystals, and understanding these forces is
      paramount for the design and utilisation of such materials. Monosodium glutamate
      monohydrate and monopotassium glutamate monohydrate are two solids that form
      significantly different structures with correspondingly dissimilar dynamics,
      while their chemistry only differs in cation identity. Crystals of each were
      characterised experimentally with single-crystal X-ray diffraction and terahertz
      time-domain spectroscopy and theoretically using solid-state density functional
      theory simulations, in order to explain the observed differences in their bulk
      properties. Specifically, crystal orbital overlap and Hamiltonian population
      analyses were performed to examine the role that the individual interactions
      between the cation and anion played in the solid-state structures and the overall
      energetic profiles of these materials.

PMID- 29043316
TI  - Polyaniline decorated Bi2MoO6 nanosheets with effective interfacial charge
      transfer as photocatalysts and optical limiters.
AB  - Polyaniline (PANI)-decorated Bi2MoO6 nanosheets (BMO/PANI) were prepared by a
      facile solvothermal method. Different characterization techniques, including X
      ray powder diffraction, scanning electron microscopy, transmission electron
      microscopy, Raman spectroscopy, Fourier transform infrared spectroscopy, X-ray
      photoelectron spectroscopy, diffuse reflectance ultraviolet-visible spectroscopy,
      photoluminescence spectroscopy, electrochemical impedance spectroscopy,
      photocurrent spectroscopy, and nanosecond time-resolved emission studies, have
      been employed to investigate the structure, optical and electrical properties of
      the BMO/PANI composites. The wide absorption of the samples in the visible light
      region makes them suitable for nonlinear transmission and photocatalytic activity
      studies. The associated photocatalytic activity and optical nonlinearities for
      the BMO/PANI composites are shown to be dependent on the PANI loadings. The
      rational mechanisms responsible for deteriorating pollutants and improving
      optical nonlinearities were also proposed, which could be mainly attributed to
      the efficient interfacial charge transfer and the interfacial electronic
      interactions between PANI and Bi2MoO6. The photoluminescence spectroscopy,
      electrochemical impedance spectroscopy, and photocurrent spectroscopy studies
      confirmed that the interface charge separation efficiency was greatly improved by
      coupling Bi2MoO6 with PANI. The tuning of photocatalysis and nonlinear optical
      behaviors with variation in the content of PANI provides an easy way to attain
      tunable properties, which are exceedingly required in optoelectronics
      applications.

PMID- 29043317
TI  - Temperature-responsive split aptamers coupled with polymerase chain reaction for
      label-free and sensitive detection of cancer cells.
AB  - A label-free and general thermo-controlled split apta-PCR strategy was first
      developed for the sensitive and specific detection of cancer cells. By
      integrating the temperature-responsive function of split aptamers with PCR
      amplification, a facile fluorescence assay of liver cancer SMMC-7721 cells was
      successfully realized with the detection of as low as 100 cells.

PMID- 29043318
TI  - Tailoring the input impedance of FeCo/C composites with efficient broadband
      absorption.
AB  - Proper impedance matching and strong attenuation capabilities are crucial factors
      for an excellent microwave absorbent. Significant attention and effort have been
      focused on the attenuation capabilities, whereas little attention has been paid
      to impedance matching, which is particularly important to design broadband
      absorbing materials. In this study, coin-like porous FeCo/C composites were
      successfully prepared by a simple carbon thermal reduction method. The Zin/Zo
      values of the FeCo/C composites were calculated to investigate the effects of the
      Fe/Co molar ratio and structure on the impedance matching. The results show that
      the coin-like porous samples were equipped with optimal impedance matching
      (Zin/Zo ~ 1) and broad frequency bandwidth. The coin-like porous structure can
      induce multiple scattering and extend the travel path of the waves, which is in
      favour of electromagnetic loss. In this way, the effective frequency bandwidth
      (RL < -10 dB) as large as 6 GHz (from 11.36 to 17.36 GHz) has been achieved at a
      thickness of 2 mm when the Fe/Co molar ratio is 4 : 6. In addition, the average
      frequency broadband reached 5.57 GHz in the thickness range of 2-2.6 mm. We
      believe that this study may provide a new strategy for tuning the impedance
      matching for optimal broadband absorbers.

PMID- 29043319
TI  - Triple function nanocomposites of porous silica-CoFe2O4-MWCNTs as a carrier for
      pH-sensitive anti-cancer drug controlled delivery.
AB  - Cobalt ferrite nanoparticles loaded on multiwalled carbon nanotube (MWCNT)
      magnetic hybrids have been demonstrated to be promising magnetic resonance
      imaging contrast agents and drug carriers. However, the hydrophobic, less
      biocompatible characteristics and low loading capacity for the drug hamper their
      wide biological applications. To solve the above problem, an alternative strategy
      is to coat the MWCNTs@CoFe2O4 nanoparticles with a mesoporous silica (mSiO2)
      shell. Herein, the reasonable fabrication process results in successful coating
      mSiO2 on the as-obtained MWCNTs@CoFe2O4 nanoparticles, forming well-defined core
      shell-structured MWCNTs@CoFe2O4@mSiO2 nanocomposites. The as-synthesized
      mesoporous nanocarrier possesses a high surface area and large pore volume for
      the loading of the drug, and has a superparamagnetic feature for drug targeting.
      Moreover, the anticancer drug doxorubicin (DOX)-loaded MWCNTs@CoFe2O4@mSiO2
      nanoplatforms show an excellent pH-responsive drug release character within 48 h.
      Therefore, a novel nanocarrier based on MWCNTs@CoFe2O4@mSiO2 was proposed, and
      its potential application for targeted cancer therapy was highlighted.

PMID- 29043320
TI  - Efficient and selective catalysis for hydrogenation and hydrosilation of alkenes
      and alkynes with PNP complexes of scandium and yttrium.
AB  - Scandium and yttrium congeneric complexes, supported by a monoanionic PNP ligand,
      were studied as catalysts for alkene hydrogenation and hydrosilation, and alkyne
      semihydrogenation and semihydrosilation. The yttrium congener was found to be
      much more active in all cases, but this greater activity is accompanied by more
      rapid catalyst decomposition and therefore higher total yields for some of the
      reactions with the scandium catalyst. Calculations indicate that the reactions
      may proceed via sigma-bond metathesis of the alkyl complexes to form metal
      hydride intermediates into which alkenes/alkynes insert.

PMID- 29043321
TI  - Tetraarylsuccinonitriles as mechanochromophores to generate highly stable
      luminescent carbon-centered radicals.
AB  - This communication reports on the design and synthesis of mechanochromophores
      with a dynamic covalent system composed of a tetraarylsuccinonitrile skeleton
      that generate a metastable organic luminescent carbon radical. The mechanically
      generated radical species showed pink color and yellow light emission under UV
      irradiation. Unusually high stability of the luminescent carbon-centered radicals
      was also observed in a polymer system.

PMID- 29043322
TI  - Chirality in adsorption on solid surfaces.
AB  - In the present review we survey the main advances made in recent years on the
      understanding of chemical chirality at solid surfaces. Chirality is an important
      topic, made particularly relevant by the homochiral nature of the biochemistry of
      life on Earth, and many chiral chemical reactions involve solid surfaces. Here we
      start our discussion with a description of surface chirality and of the different
      ways that chirality can be bestowed on solid surfaces. We then expand on the
      studies carried out to date to understand the adsorption of chiral compounds at a
      molecular level. We summarize the work published on the adsorption of pure
      enantiomers, of enantiomeric mixtures, and of prochiral molecules on chiral and
      achiral model surfaces, especially on well-defined metal single crystals but also
      on other flat substrates such as highly ordered pyrolytic graphite. Several
      phenomena are identified, including surface reconstruction and chiral imprinting
      upon adsorption of chiral agents, and the enhancement or suppression of
      enantioselectivity seen in some cases upon adsorption of enantiomixtures of
      chiral compounds. The possibility of enhancing the enantiopurity of adsorbed
      layers upon the addition of chiral seeds and the so-called "sergeants and
      soldiers" phenomenon are presented. Examples are provided where the chiral
      behavior has been associated with either thermodynamic or kinetic driving forces.
      Two main approaches to the creation of enantioselective surface sites are
      discussed, namely, via the formation of supramolecular chiral ensembles made out
      of small chiral adsorbates, and by adsorption of more complex chiral molecules
      capable of providing suitable chiral environments for reactants by themselves,
      via the formation of individual adsorbate:modifier adducts on the surface.
      Finally, a discussion is offered on the additional effects generated by the
      presence of the liquid phase often required in practical applications such as
      enantioselective crystallization, chiral chromatography, and enantioselective
      catalysis.

PMID- 29043323
TI  - Concomitant polymorphism and the martensitic-like transformation of an organic
      crystal.
AB  - Crystalline polymorphism is a phenomenon that occurs in many molecular solids,
      resulting in a diverse range of possible bulk structures. Temperature and
      pressure can often be used to thermodynamically control which crystal form is
      preferred, and the associated transitions between polymorphic phases are often
      discontinuous and complete. N-Methyl-4-carboxypyridinium chloride is a solid that
      undergoes an apparent continuous temperature-dependent phase transition from an
      orthorhombic to a monoclinic polymorph. However, a hybrid characterization
      approach using single-crystal X-ray diffraction, terahertz time-domain
      spectroscopy, and solid-state density functional theory reveals the
      transformation to be actually a slowly changing ratio of the two discrete
      polymorphic forms. The potential energy surface of this process can be directly
      accessed using terahertz radiation, and the data show that a very low barrier
      (43.3 J mol-1) exists along the polymorph transformation coordinate.

PMID- 29043324
TI  - Privileged hydration sites in aromatic side chains: effect on conformational
      equilibrium.
AB  - Water interaction with peptide chains is one of the key structure stabilizing
      factors in an aqueous environment. Because of its strong polar character, water
      can bind to both anionic and cationic sites via electrostatic interactions. It
      can also act as a hydrogen-bond donor or acceptor according to its interactions
      with different polar groups in the backbone and side chains of peptides and
      proteins. Based on density functional theory calculations, the present report
      aims at illustrating the most energetically favorable interaction sites of
      aromatic side chains of phenylalanine, tyrosine, tryptophan, and histidine
      (neutral and protonated species) with surrounding water molecules. It was shown
      that beyond the strong interactions occurring between water and the aromatic ring
      acceptor/donor sites, such as O-H, N-H and -N[double bond, length as m-dash]
      groups, weaker interactions with pi-electron clouds should also be considered.
      The latter type of binding, hereafter referred to as Hwpi interaction, involves
      one of the water hydrogen atoms (Hw) pointing toward the aromatic ring. Upon
      comparison between the theoretical data obtained from a purely implicit hydration
      model, i.e. a polarized solvent continuum, and those collected from a mixture of
      implicit and explicit hydration models, it has been shown that the explicit water
      molecule binding to aromatic rings affects the relative energies of the rotamers
      generated by the two side chain torsion angles (chi1 and chi2).

PMID- 29043325
TI  - A fully integrated microfluidic platform for highly sensitive analysis of
      immunochemical parameters.
AB  - We present a novel fully integrated centrifugal microfluidic platform for highly
      sensitive immunoassays in point-of-care settings. The platform consists of a
      disposable cartridge containing structures for assay processing, a porous
      membrane and all dried reagents required for the analysis. Additionally, a
      blister containing a washing buffer is connected to a new aliquoting structure
      enabling the serial aliquoting of washing buffer for repetitive bound-free
      separation steps. The proof-of-concept for two immunoassays is shown in the
      cartridge with each requiring only 30 MUL of whole blood or plasma as the sample
      material. The detection of the cardiac marker Troponin T with a functional
      sensitivity of 7.55 ng L-1 (cv = 10%) within 11 minutes is shown based on samples
      from ten donors which were measured with six breadboard instruments to prove the
      platform capability for highly sensitive measurements at diagnostic relevant
      concentrations. Furthermore an assay for the cardiac marker NT-proBNP (five
      donors, six instruments) with a time-to-result of 12 minutes demonstrates that
      high-titer analytes (43 to 16.566 ng L-1) can be measured as well. A method
      comparison of our platform with a state-of-the-art laboratory analyzer proves an
      excellent correlation of the measured analyte concentrations. All results are
      obtained from injection moulded cartridges and all components of the platform are
      compatible for mass production.

PMID- 29043326
TI  - Symmetrical or non-symmetrical luminescent turnstiles based on hydroquinone
      stators and rotors bearing pyridyl or p-dimethylaminopyridyl coordinating units.
AB  - The design and synthesis of a novel family of molecular turnstiles T1-T5 were
      achieved. All five turnstiles are based on a stator and a rotor covalently
      interconnected. While turnstiles T1-T2 are based on a symmetric stator equipped
      with two coordinating pyridyl units and a rotor bearing either a pyridyl or p
      dimethylaminopyridyl coordinating moiety, the two non-symmetric turnstiles T4 and
      T5 are based on a stator bearing only a single pyridyl unit and the same rotor as
      T1 and T2 mentioned above. The switching between the open (T1-T5) and the closed
      (T-M) states of the turnstiles by metal cations (M = Ag+ or Pd2+) was
      investigated in solution by using 1D and 2D NMR techniques. The locking of the
      rotational movement leading to the closed state of the turnstile was achieved
      upon addition of the Ag+ cation through its simultaneous binding by both pyridyl
      moieties of the stator and the rotor. The unlocking process leading back to the
      open state was achieved by the addition of Et4NBr. For the symmetric turnstiles
      T1 and T2, bearing two pyridyl units on the stator, the binding of the Ag+ cation
      leads to an oscillating phenomenon between the two energetically equivalent
      closed states. However, in the case of turnstile T1, the oscillating process
      could be prevented by blocking the rotational movement using PdCl2 as the locking
      agent. Owing to the emissive nature of the stator, the open and closed states of
      the turnstiles were investigated by steady state and time-resolved photophysical
      methods. The photo-excitation of the turnstiles in their open state leads to an
      intense near-UV to deep-blue emission with short-lived excited states and a
      singlet intra-ligand charge transfer (1ILCT) character. Upon binding of the Ag+
      cation, sizeable bathochromic shifts and a substantial decrease of PLQY were
      observed. Finally, the coordination of PdCl2, which possesses lower-lying excited
      states with metal-centered (MC) and ligand-to-metal charge transfer (LMCT)
      character, completely quenches the photoluminescence.

PMID- 29043327
TI  - Stacking interactions involving non-Watson-Crick basepairs: dispersion corrected
      density functional theory studies.
AB  - The G:A basepair, stabilized by hydrogen bonding through the sugar edge of
      guanine and Hoogsteen edge of adenine in trans orientation (G:A S:HT), appears
      very frequently in the solved RNA structures and is very stable. We have carried
      out stacking energy analyses of two sequences, namely C:G W:WC::G:A S:HT and G:C
      W:WC::G:A S:HT (':' represents basepairing and '::' represents stacking
      interactions), formed by this non-Watson-Crick basepair, by DFT-D. We have
      scanned nearly the complete phase space by modeling structures of these sequences
      using different values of the basepair orientation parameters to determine the
      most stable conformations. It is found that the most stable conformations are
      rather far from the most frequently found orientations. We have considered the
      effect of sugar-phosphate backbone connectivity as an energy penalty arising from
      deformation of pseudo bond lengths between C1' atoms of successive bases along
      the strands. Augmentation of stacking energy from DFT-D by this coarse grain
      energy gives predicted structures extremely similar to the experimentally
      determined ones. It has been observed that the best stacking with small twist
      values is associated with positive roll and negative slide values, which are
      similar to their values in A-RNA structures for most sequences. Among the two
      base pair steps, C:G W:WC::G:A S:HT appears to be more stable in terms of
      stacking energy as compared to G:C W:WC::G:A S:HT possibly due to larger stacking
      overlap in the former one.

PMID- 29043328
TI  - Catalytic applications of small bite-angle diphosphorus ligands with single-atom
      linkers.
AB  - Diphosphorus ligands connected by a single atom (R2PEPR2; E = CR2, C[double bond,
      length as m-dash]CR2 and NR) give chelating ligands with very small bite-angles
      (natural bite-angle of 72 degrees  for dppm) as well as enable access to other
      properties such as bridging modes and hemilability. Their use in catalysis has
      been growing over the last two decades as researchers have sought to apply the
      properties of small bite-angle ligands to a wide number of catalytic reactions,
      often complementing the well-established applications of wide bite-angle ligands
      in catalysis. This Perspective reviews the properties of diphosphorus ligands
      featuring a single-atom linker and their use in several catalytic transformations
      of alkenes, including selective ethene oligomerisation, ethene polymerisation and
      co-polymerisation with CO, hydroacylation and hydrogenation, as well as their use
      in transfer hydrogenation and hydrogen-borrowing reactions.

PMID- 29043329
TI  - ScMO(BO3) (M = Ca and Cd): new Sc-based oxyborates featuring interesting edge
      sharing sandwich-like chains and UV cut-off edges.
AB  - Two new isostructural rare-earth oxyborates ScMO(BO3) (M = Ca and Cd) with a
      three-dimensional (3D) cationic framework and parallel arranged [BO3] triangles
      have been synthesized by the flux method. In the 3D cationic framework, an
      interesting sandwich-like basic building unit (BBU) is constructed by two
      [Ca(1)O4]6- chains and two [Sc(1)O4]5- chains. ScMO(BO3) melt incongruently,
      which shows that title compounds can be grown by the flux method. The UV cut-off
      edges for ScCaO(BO3) and ScCdO(BO3) are 230 and 249 nm, respectively. In
      addition, the first-principles calculations are performed to gain further
      insights into the relationship between the microscopic electronic structures and
      associated optical properties.

PMID- 29043330
TI  - Procyanidins extracted from the litchi pericarp ameliorate atherosclerosis in
      ApoE knockout mice: their effects on nitric oxide bioavailability and oxidative
      stress.
AB  - Epidemiological studies strongly support the role of procyanidin-rich beverages
      and fruit in the prevention of cardiovascular diseases. Procyanidins extracted
      from the litchi pericarp (LPPC), a new source of procyanidins, were isolated and
      identified in our laboratory and have been proven to possess strong antioxidant
      activity in vitro. In the present study, we investigated the anti-atherosclerotic
      effects of LPPC in apolipoprotein E knockout (ApoE KO) mice fed a high fat diet
      for 24 weeks. LPPC (100 mg kg-1 body mass daily) significantly reduced the
      atherosclerotic lesion size (P < 0.01 versus ApoE KO mice), excess NO production
      and iNOS expression. Moreover, the mRNA and protein expressions of eNOS in the
      aortas of ApoE KO mice were increased by LPPC which further explains the
      endothelial protective action of LPPC. LPPC also showed profound antioxidant
      effects in ApoE KO mice. Plasma TBARS contents and the mRNA expression for NADPH
      oxidase (p47phox, p67phox, NOX-2/gp91phox and NOX-4) in the aortas of ApoE KO
      mice were significantly reduced, whereas plasma SOD activity was markedly
      elevated by LPPC. These results elucidated that LPPC could ameliorate
      atherosclerosis in ApoE-KO mice by improving NO bioavailability and reducing
      oxidative stress through NADPH oxidase-dependent mechanisms.

PMID- 29043331
TI  - MU-Pyridine-bridged copper complex with robust proton-reducing ability.
AB  - The binuclear copper complex [Cu(DQPD)]2 (where DQPD = deprotonated N2,N6
      di(quinolin-8-yl)pyridine-2,6-dicarboxamide (DQPDH2)) was synthesised and
      characterised by various spectroscopic as well as electrochemical techniques. The
      binuclear copper complex was converted into a mononuclear one by the addition of
      2 equivalents of pTsOH into [Cu(DQPD)]2. The interconversion between the dimer
      and monomer complex was studied through UV-Vis spectroscopy and cyclic
      voltammetry. The mononuclear copper complex showed high catalytic activity
      towards electrochemical proton reduction using acetic acid as the external proton
      source in 95 : 5 (v/v) DMF/H2O. It showed an ic/ip (where ic is the catalytic
      current in the presence of acetic acid and ip is the reduction peak current in
      absence of acid) value of 24 and a turnover rate (TOF) of 111.70 s-1 at a scan
      rate of 100 mV s-1 at 25  degrees C. The [Cu(DQPD)]2 complex evolved hydrogen
      under the irradiation of visible light in the presence of fluorescein (Fl) as a
      photosensitizer and triethylamine (TEA) as the sacrificial electron donor with an
      initial TOF of 0.03 s-1 with respect to the catalyst.

PMID- 29043332
TI  - Enhanced thermoelectric performance in ternary spinel Cu4Mn2Te4via the
      synergistic effect of tellurium deficiency and chlorine doping.
AB  - The chemistry of copper-based chalcogenides has received considerable attention
      due to their diverse structures and potential applications in the area of
      thermoelectric (TE) materials. In this communication, a series of spinel-type
      Cu4Mn2Te4-based samples have been successfully prepared and their high TE
      performances are attributed to the enhanced power factor and low thermal
      conductivity via the synergistic effect of Te deficiency and Cl doping.
      Consequently, a maximum TE figure of merit (ZT) of ~0.4 was achieved for the
      Cu4Mn2Te3.93Cl0.03 sample at 700 K, which was about 100% enhanced in comparison
      with the undoped Cu4Mn2Te4 sample and one of the highest ZT values reported for p
      type spinel tellurides.

PMID- 29043333
TI  - Nanostructured N-doped orthorhombic Nb2O5 as an efficient stable photocatalyst
      for hydrogen generation under visible light.
AB  - The synthesis of orthorhombic nitrogen-doped niobium oxide (Nb2O5-xNx)
      nanostructures was performed and a photocatalytic study carried out in their use
      in the conversion of toxic H2S and water into hydrogen under UV-Visible light.
      Nanostructured orthorhombic Nb2O5-xNx was synthesized by a simple solid-state
      combustion reaction (SSCR). The nanostructural features of Nb2O5-xNx were
      examined by FESEM and HRTEM, which showed they had a porous chain-like structure,
      with chains interlocked with each other and with nanoparticles sized less than 10
      nm. Diffuse reflectance spectra depicted their extended absorbance in the visible
      region with a band gap of 2.4 eV. The substitution of nitrogen in place of oxygen
      atoms as well as Nb-N bond formation were confirmed by X-ray photoelectron
      spectroscopy (XPS) and Raman spectroscopy. A computational study (DFT) of Nb2O5
      xNx was also performed for investigation and conformation of the crystal and
      electronic structure. N-Substitution clearly showed a narrowing of the band gap
      due to N 2p bands cascading above the O 2p band. Considering the band gap in the
      visible region, Nb2O5-xNx exhibited enhanced photocatalytic activity toward
      hydrogen evolution (3010 MUmol h-1 g-1) for water splitting and (9358 MUmol h-1 g
      1) for H2S splitting under visible light. The enhanced photocatalytic activity of
      Nb2O5-xNx was attributed to its extended absorbance in the visible region due to
      its electronic structure being modified upon doping, which in turn generates more
      electron-hole pairs, which are responsible for higher H2 generation. More
      significantly, the mesoporous nanostructure accelerated the supression of
      electron and hole recombination, which also contributed to the enhancement of its
      activity.

PMID- 29043334
TI  - Efficient orange-red electroluminescence of iridium complexes with 1-(2,6
      bis(trifluoromethyl)pyridin-4-yl)isoquinoline and 4-(2,6
      bis(trifluoromethyl)pyridin-4-yl)quinazoline ligands.
AB  - Two novel iridium(iii) complexes, Ir(tfmpiq)2(acac) (tfmpiq = 1-(2,6
      bis(trifluoromethyl)pyridin-4-yl)isoquinoline, acac = acetylacetone) and
      Ir(tfmpqz)2(acac) (tfmpqz = 4-(2,6-bis(trifluoromethyl)pyridin-4-yl)quinazoline),
      were synthesized and thoroughly investigated. Both complexes emit orange-red
      photoluminescence with high quantum yields (Ir(tfmpiq)2(acac): lambdamax: 587 nm,
      etaPL: 42%; Ir(tfmpqz)2(acac): lambdamax: 588 nm, etaPL: 91%). Furthermore, the
      complex containing quinazoline shows higher electron mobility than that with
      isoquinoline. The organic light-emitting diodes (OLEDs) with single- or double
      emitting layers (EML) were fabricated using two new emitters. The double-EML
      device using Ir(tfmpqz)2(acac) with the structure of ITO (indium-tin-oxide)/MoO3
      (molybdenum oxide, 3 nm)/TAPC (di-[4-(N,N-ditolyl-amino)-phenyl]cyclohexane, 50
      nm)/Ir(tfmpqz)2(acac) (1 wt%):TcTa (4,4',4''-tris(carbazole-9-yl)triphenylamine,
      10 nm)/Ir(tfmpqz)2(acac) (1 wt%):2,6DCzPPy (2,6-bis(3-(carbazol-9
      yl)phenyl)pyridine, 10 nm)/TmPyPB (1,3,5-tri(m-pyrid-3-yl-phenyl)benzene, 50
      nm)/LiF (1 nm)/Al (100 nm) displays good electroluminescence performances with a
      maximum luminance of 96 609 cd m-2, a maximum current efficiency of 59.09 cd A-1,
      a maximum external quantum efficiency of 20.2%, a maximum power efficiency of
      53.61 lm W-1, and the efficiency roll-off ratio is mild.

PMID- 29043335
TI  - Remarkable lowering in the synthesis temperature of LiMn2O4via citrate solution
      gel synthesis facilitated by ethanol.
AB  - LiMn2O4 (LMO) is interesting from the viewpoint of its energy storage
      applications as it is a cathode in lithium ion batteries (LIB), which contains no
      rare, toxic or expansive elements, while it provides a high theoretical capacity
      (148 mA h g-1) at a reasonable voltage (4 V region) and a higher thermal
      stability compared to cobalt based cathodes and has a good rechargeability and
      cycling stability due to its spinel structure. Low temperature synthesis routes
      for cathode materials are currently gaining attention, in order to decrease the
      ecological footprint of the final LIB. Here, the crystallization temperature of
      LMO by a citrate based solution-gel synthesis was significantly lowered, to as
      low as 250  degrees C by the addition of ethanol to the precursor. The role of
      ethanol in this synthesis process was explored. It was found to lead to a
      considerable increase in the oxidation rate of the redox couple Mn2+/Mn3+, a
      lowering of the precursor decomposition temperature by 200  degrees C, besides a
      drastic decrease in the crystallization temperature (reaching 250  degrees C).
      Moreover, the main cause was identified to be an esterification reaction of
      ethanol with the carboxylic acid in the precursor complexes, taking place before
      the oxide formation. The insights obtained strengthen the knowledge regarding
      citrato-Mn2+/Mn3+ complexes present in aqueous solution-gel synthesis routes and
      are relevant for the preparation of various manganese containing oxides.
      Moreover, the precursor developed opens up a new possibility for the low
      temperature synthesis of LMO powders and thin films for application in LIB. In
      the case of thin film batteries, the low temperature processing provides
      compatibility with other materials in the thin film battery stack, avoiding
      undesired oxidations or interfacial reactions.

PMID- 29043336
TI  - On verdigris, part I: synthesis, crystal structure solution and characterisation
      of the 1-2-0 phase (Cu3(CH3COO)2(OH)4).
AB  - Known synthesis approaches for basic copper(ii) acetates, the main components of
      historic verdrigis pigments were reinvestigated and revealed to be partially
      irreproducible. A modification of the reaction conditions led to the successful
      and reproducible synthesis of the 1-2-0 phase (Cu3(CH3COO)2(OH)4 =
      1Cu(CH3COO)2.2Cu(OH)2.0H2O). The phase composition was derived from elemental and
      thermal analysis and confirmed by the crystal structure solution using
      synchrotron X-ray powder diffraction (XRPD) data. The 1-2-0 phase crystallises in
      space group Pbca with lattice parameters of a = 20.9742(1) A, b = 7.2076(1) A,
      and c = 13.1220(1) A. The crystal structure consists of Cu2(CH3
      COO)2(OH)4/3(OH)2/21/3- dimers, which are interconnected by corner sharing
      Cu(OH)2/3(OH)2/21/3+ squares forming layers perpendicular to the a-axis. The deep
      blue color of the solid originates from a reflectance maximum at 472 nm and from
      an absorbance maximum at 676 nm that is comparable with other historic blue
      pigments like azurite or Egyptian blue. IR- and Raman-spectroscopic properties of
      the solid were investigated as well, which demonstrated that the obtained product
      is identical with a previously synthesised verdigris phase that was obtained by
      applying historical procedures. Therefore, our reference data for the title
      compound will help to improve the understanding of the multiphase mixtures
      occurring in historic verdigris samples. The magnetic properties of the 1-2-0
      phase were also investigated. At low temperatures the magnetic susceptibility is
      well described by a spin-1/2 Heisenberg chain with uniform antiferromagnetic
      nearest-neighbour spin exchange coupling of only one of three Cu magnetic
      moments. Due to the very strong antiferromagnetic coupling of the Cu2(CH3
      COO)2(OH)4/3(OH)2/21/3- dimers their contribution to magnetism becomes relevant
      above ~140 K, which results in the presence of two distinct temperature regions
      where Curie-Weiss behaviour of the magnetic susceptibility with different Curie
      constants and Weiss temperatures is found.

PMID- 29043337
TI  - Tethered cationic alkaline earth - olefin complexes.
AB  - The aminofluoroalcohol N,N,N-(CH2[double bond, length as m-dash]CHCH2CH2
      ),(CH3OCH2CH2-),(HOC(CF3)2CH2-)N ({ROF}H) possessing both a methoxy and an olefin
      dangling side arms enables the preparation of the heteroleptic charge neutral
      alkaline earth complexes [{MU2-ROF}AeN(SiMe2H)2]2 (Ae = Ca, 1; Sr, 2). These O
      bridged dinuclear complexes were characterised by NMR spectroscopy and X-ray
      diffraction crystallography. XRD analysis of 1 and 2 showed that both complexes
      are stabilised by intramolecular AeF-C and beta-agostic AeH-Si secondary
      interactions, and that the olefin does not bind to the alkaline earths while the
      methoxy side-arm does. The discrete ion pairs [({MU2
      ROF}Ae.(Et2O)2)2]2+.2[H2N{B(C6F5)3}2]- (Ae = Ca, 3a; Sr, 4a) were synthesised
      upon treatment of the parent complexes 1 and 2 by [H.(Et2O)2]+.[H2N{B(C6F5)3}2]-.
      NMR spectroscopy showed the presence of two coordinated Et2O molecules on each
      metal in these complexes. The water adduct [({MU2
      ROF}Sr.(H2O))2]2+.2[H2N{B(C6F5)3}2]- (4b), presumably derived from 4a upon
      adventitious introduction of moisture during recrystallisation, was characterised
      by crystallographic methods. The dication [({MU2-ROF}Sr.(H2O))2]2+ exists as an O
      bridged dinuclear species featuring very strong intramolecular SrF-C interactions
      in the range 2.788(5)-2.997(6) A, and no interaction with the weakly coordinating
      anion. Perhaps more importantly, the tethered olefins are coordinated onto the
      metal cations, with short SrCpi interactions in the range 3.066(10)-3.092(10) A;
      this represents the first example of a Sr-olefin cationic complex. Hence,
      cationisation of the charge neutral precursor to generate the discrete ion pair
      increases electron deficiency at the metal centre, resulting in the first
      observation of the binding of an olefin onto a well-defined cationic heavy
      alkaline earth. On the other hand, our attempts to produce Ae-olefin cations
      devoid of coordinated Lewis base with this strategy have met no success so far.

PMID- 29043338
TI  - Solvent-driven azide-induced mononuclear discrete versus one-dimensional
      polymeric aromatic Mobius cadmium(ii) complexes of an N6 tetradentate helical
      ligand.
AB  - We report the synthesis and structural characterization of a heteroleptic
      mononuclear discrete complex [Cd(N3)2(L)(MeOH)].MeOH (1.MeOH) and a one
      dimensional coordination polymer of the composition [Cd3(N3)6(L)]n (2),
      fabricated from Cd(NO3)2.4H2O and the helical organic ligand benzilbis((pyridin-2
      yl)methylidenehydrazone) (L) in the presence of two equivalents of NaN3. The
      formation of different structures is driven by the solvent. The former complex is
      formed in the presence of MeOH, while the latter complex is formed in EtOH. The
      CdII centre in 1.MeOH is trapped by the two pyridyl-imine units of the
      tetradentate ligand L, two azide ligands and one oxygen atom of one methanol
      ligand with the CdN6O coordination polyhedron yielding a square face monocapped
      trigonal prism. The asymmetric unit of 2 consists of three symmetrically
      independent atoms of CdII, six azide anions and one L. The polymeric structure of
      2 is realized through chains of the Cd(N3)2 units which are decorated with
      Cd(N3)2L units. The CdII atoms from the backbone of the coordination polymer have
      a distorted octahedral coordination, while the remaining CdII atom forms a
      trigonal prism with two basal planes nearly parallel to each other. In both
      complexes, the 12pi electron chelate ring of the CdL fragment is shown to be
      aromatic by establishing it as a Mobius object. Hirshfeld surface analysis of 1
      in 1.MeOH and L in 2 showed that the structures of both species are highly
      dominated by HX (X = H, C and N) contacts, of which the latter two are highly
      favoured, as well as some contribution from highly enriched CC contacts is
      clearly observed.

PMID- 29043339
TI  - MicroRNA detection at femtomolar concentrations with isothermal amplification and
      a biological nanopore.
AB  - One of the greatest challenges faced by chemists and biologists is the detection
      of molecules at extremely low concentrations. This paper describes a method to
      detect ultra-low concentrations (1 femtomole) of nucleotides using isothermal
      amplification and a biological nanopore.

PMID- 29043340
TI  - CFA-13 - a bifunctional perfluorinated metal-organic framework featuring active
      Cu(i) and Cu(ii) sites.
AB  - The synthesis and crystal structure of the mixed-valent perfluorinated metal
      organic framework (Me2NH2)[CFA-13] (Coordination Framework Augsburg University
      13), (Me2NH2)[CuCu(tfpc)4] (H2-tfpc = 3,5-bis(trifluoromethyl)-1H-pyrazole-4
      carboxylic acid) is described. The copper-containing MOF crystallizes in the
      monoclinic crystal system within the space group P21/n (no. 14) and the unit cell
      parameters are as follows: a = 22.3887(19), b = 13.6888(8), c = 21.1804(13) A,
      beta = 90.495(3) degrees , V = 6491.0(8) A3. (Me2NH2)[CFA-13] features a porous 3
      D structure constructed from two types of secondary building units (SBUs).
      Besides novel trinuclear [Cu(pz)4]- coordination units, the network also exhibits
      Cu(ii) paddle-wheel SBUs. (Me2NH2)[CFA-13] is fully characterized by single
      crystal X-ray diffraction, thermogravimetric analysis, variable temperature
      powder X-ray diffraction, IR spectroscopy, photoluminescence, gas sorption
      measurements and pulse chemisorption experiments. M[CFA-13] (M = K+, Cs+)
      frameworks were prepared by postsynthetic exchange of interchannel
      dimethylammonium cations. Moreover, it was shown that CO molecules can be
      selectively bound at Cu(i) sites of [Cu(pz)4]- units, whereas Cu(ii) paddle-wheel
      units bind selectively NH3 molecules.

PMID- 29043341
TI  - The facile synthesis of layered Ti2C MXene/carbon nanotube composite paper with
      enhanced electrochemical properties.
AB  - Ti2AlC has been investigated for several decades, but much less attention has
      been paid to its delamination and potential energy storage applications, mainly
      due to the difficulty of delamination and its oxidation features. Herein, a new
      path to enhance exfoliation and delamination of two-dimensional (2D) Ti2CTx MXene
      is used. By using an etchant of HCl + LiF, multilayer Ti2CTx is easy to obtain.
      With only the assistance of mild sonication for 1.5 h without any additional
      intercalation, two-dimensional (2D) Ti2CTx flake suspensions are produced.
      Subsequently, the as-fabricated stable suspensions of delaminated Ti2CTx flakes
      are combined with carbon nanotubes. After filtration, a two-dimensional layered
      Ti2CTx/carbon nanotube (CNT) nanocomposite "paper" is prepared. Owing to the
      larger specific area of MXene flakes, which is caused by the complete exfoliation
      of MXene, with carbon nanotubes assisting with structural support between layers
      to prevent restacking, this structure provides a rapid charge transfer path
      during electrochemical reactions. When the nanocomposite paper is used as a
      lithium ion battery anode, it exhibits a higher capacitance and better cycling
      stability (a reversible capacity of 155.5 mA h g-1 at 100 mA g-1 after 200
      cycles). Moreover, the "paper" can be directly used for electrodes in
      supercapacitors; the calculated capacitances are 515.3 F g-1 and 694 F cm-3 at a
      scanning rate of 2 mV s-1. The facile synthesis of layered Ti2C MXene/carbon
      nanotube nanocomposite paper provides a more secure and easy way to fabricate
      promising energy storage materials, and creates wider opportunities for
      exploiting the potential of other MXenes.

PMID- 29043342
TI  - Antihypertensive effects of Tartary buckwheat flavonoids by improvement of
      vascular insulin sensitivity in spontaneously hypertensive rats.
AB  - Vascular insulin resistance and oxidative stress contribute to endothelial
      dysfunction and hypertension. The present study investigated whether chronic
      treatment with purified Tartary buckwheat flavonoids fraction (TBF) prevents the
      development of hypertension via improving vascular insulin sensitivity and
      reducing oxidative stress. Six-week-old male spontaneously hypertensive rats
      (SHRs) and their normotensive Wistar-Kyoto (WKY) control rats were subjected to
      different dosages of TBF for 8 weeks. Blood pressure, mesenteric arteriolar
      vasorelaxation, superoxide anion (O2-) generation, NAD(P)H oxidase activity, and
      insulin-stimulated Akt/endothelial nitric oxide synthase (eNOS) activation and
      nitric oxide (NO) production were determined. The SHRs had higher systolic blood
      pressure, systemic insulin resistance, and impaired vasodilator actions of
      insulin and the insulin signaling pathway in mesenteric arterioles when compared
      with the WKY rats. TBF treatment at a dosage of 100 mg kg-1 day-1 significantly
      reduced systolic blood pressure and increased vasodilator response to insulin in
      the SHRs. Additionally, TBF treatment significantly reduced phosphorylation of
      insulin receptor substrate 1 (IRS-1) at serine 307 and increased insulin
      stimulated Akt/eNOS activation in the SHRs. Furthermore, TBF treatment reduced
      the overproduction of basal O2- in association with a reduction of NAD(P)H
      oxidase activity in mesenteric arterioles of the SHRs. Finally, quercetin was
      identified as the predominant active component of TBF in attenuating the
      development of hypertension with regard to reducing vascular oxidative stress,
      regulating the vascular insulin signaling pathway and restoring vasodilator
      response to insulin in the SHRs. In conclusion, TBF possesses protective effects
      against hypertension through attenuating vascular insulin resistance and
      oxidative stress.

PMID- 29043343
TI  - Large-area plasmon enhanced two-dimensional MoS2.
AB  - Two-dimensional transition metal chalcogenides (2D TMDCs) show photoluminescence
      (PL) as a result of direct band-gap transitions at visible wavelengths. Although
      2D TMDCs have been considered for use in next-generation optoelectronics,
      practical applications are restricted by their low absorption and emission
      efficiency. To overcome these limitations using plasmonic local field
      enhancement, we propose the integration of gold nanoparticles with 2D TMDCs over
      a centimeter-scale area. Using self-assembled gold nanoshell monolayers, we
      produce a 10-fold increase in the PL of 2D TMDCs. We expect our method to provide
      a means for the large-area, low-cost fabrication of plasmon-enhanced 2D TMDCs for
      optoelectronic applications.

PMID- 29043344
TI  - Divalent metal ions control activity and inhibition of protein kinases.
AB  - Protein kinases are key enzymes in the regulation of eukaryotic signal
      transduction. As metalloenzymes they employ divalent cations for catalysis and
      regulation. We used the catalytic (C) subunit of cAMP-dependent protein kinase
      (PKA) as a model protein to investigate the role of a variety of physiologically
      or pathophysiologically relevant divalent metal ions in distinct steps within the
      catalytic cycle. It is established that divalent metal ions play a crucial role
      in co-binding of nucleotides and also assist in catalysis. Our studies reveal
      that besides the physiologically highly relevant magnesium, metals like zinc and
      manganese can assist in phosphoryl transfer, however, only a few support
      efficient substrate turnover (turnover catalysis). Those trace metals allow for
      substrate binding and phosphotransfer but hamper product release. We further
      established the unique role of magnesium as the common biologically relevant
      divalent metal ideally enabling (co-) substrate binding and orientation.
      Magnesium allows stable substrate binding and, on the other hand accelerates
      product release, thus being extremely efficient in turnover catalysis. We
      extended our studies to non-catalytic functions of protein kinases looking at
      pseudokinases, a subfamily of protein kinases inherently lacking critical
      residues for catalysis. Recently, pseudokinases have been linked to human
      diseases. Some pseudokinases are still capable of binding metal ions, yet have
      lost the ability to transfer the phosphoryl group from ATP to a given substrate.
      Here metal ions stabilize an active like, though catalytically unproductive
      conformation and are therefore crucial to maintain non-catalytic function.
      Finally, we demonstrate for the canonical kinase PKA that the trace metal
      manganese alone can stabilize protein kinases in an active like conformation
      allowing them to bind substrates even in the absence of nucleotides.

PMID- 29043346
TI  - Anti-obesity molecular mechanism of soy isoflavones: weaving the way to new
      therapeutic routes.
AB  - Obesity is ringing alarm bells globally. Advances in food science and nutrition
      research have been devoted to identifying food components that exert anti-obesity
      effects, as well as investigating the molecular mechanisms by which they modulate
      the progression of obesity. Soy foods have attracted much interest as high
      protein components of the human diet and as unique sources of isoflavones. As
      they have similar chemical structures to endogenous estrogens, isoflavones are
      believed to interact with intracellular estrogen receptors, which results in
      reductions in the accumulation of lipids and the distribution of adipose tissue.
      Both in vitro and in vivo studies have revealed other signaling pathways in which
      isoflavones are involved in the inhibition of adipogenesis and lipogenesis by
      interacting with various transcription factors and upstream signaling molecules.
      Although the biological mechanisms that cause the biphasic effects of isoflavones
      and various controversial results remain unknown, it is noteworthy that
      isoflavones exhibit pleiotropic effects in the human body to regulate metabolism
      and balance, which may potentially prevent and treat obesity.

PMID- 29043348
TI  - Design and mechanism of core-shell TiO2 nanoparticles as a high-performance
      photothermal agent.
AB  - Photothermal agents (PTAs) with high biocompatibility and therapeutic efficacy
      have become particularly fascinating, however, knowledge of their photothermal
      performance is rather limited. Herein, rationally designed core-shell TiO2
      nanoparticles have been fabricated using a mild hydrogenation method, where NaBH4
      was used as the H2 source. The resultant TiO2 possesses strong optical absorption
      in the NIR region and remarkable photothermal conversion capability and
      stability, leading to a high inhibition rate on cancer cells. In particular, its
      photothermal conversion efficiency is as high as 55.2%, which is 204% that of the
      fully hydrogenated amorphous TiO2. More importantly, the underlying mechanism is
      proposed. It is revealed that while the oxygen vacancies induced by the
      hydrogenation can introduce defect levels in the band gap and enhance the optical
      absorption, the superfluous oxygen vacancies and defects reduce the photothermal
      conversion capability and thermal conductivity to a large extent. Controlling the
      hydrogenation degree and maintaining a certain extent of crystallization are,
      therefore, crucial to the photothermal properties. This new understanding of the
      photothermal conversion mechanism may have provided a fresh route to design and
      optimize PTAs and inspire considerable interest to turn a large variety of
      semiconductor metal oxides into competent PTAs by appropriate hydrogenation.

PMID- 29043347
TI  - Zinc'ing it out: zinc homeostasis mechanisms and their impact on the pathogenesis
      of human pathogen group A streptococcus.
AB  - Group A Streptococccus (GAS) is a major human pathogen that causes significant
      morbidity and mortality. Zinc is an essential trace element required for GAS
      growth, however, zinc can be toxic at excess concentrations. The bacterial
      strategies to maintain zinc sufficiency without incurring zinc toxicity play a
      crucial role in host-GAS interactions and have a significant impact on GAS
      pathogenesis. The host deploys nutritional immune mechanisms to retard GAS growth
      by causing either zinc deprivation or zinc poisoning. However, GAS overcomes the
      zinc-dependent host defenses and survives in the hostile environment by employing
      complex adaptive strategies. In this review, we describe the different host
      immune strategies that employ either zinc limitation or zinc toxicity in
      different host environments to control GAS infection. We also discuss the
      molecular mechanisms and machineries used by GAS to evade host nutritional
      defenses and establish successful infection. Emerging evidence suggests that the
      metal transporters are major GAS virulence factors as they compete against host
      nutritional immune mechanisms to acquire or expel metals and promote bacterial
      survival in the host. Thus, identification of GAS molecules and elucidation of
      the mechanisms by which GAS combats host-mediated alterations in zinc
      availability may lead to novel interference strategies targeting GAS metal
      acquisition systems.

PMID- 29043349
TI  - Comparative suppressing effects of black and green teas on the formation of
      advanced glycation end products (AGEs) and AGE-induced oxidative stress.
AB  - This study aimed at investigating and comparing the anti-diabetic potential of
      black and green teas. Biochemical analyses indicate higher antioxidant potency,
      significantly correlated with the phytochemicals present, in green teas compared
      to black teas. Both extracts afforded a similar level of protection to
      erythrocytes against peroxyl radical-induced lysis. Non-cytotoxic concentration
      of green and black tea extracts significantly reduced the reactive oxygen species
      (ROS) production (P < 0.01), lowered the oxidation of proteins (P < 0.05) and
      decreased the IL-6 secretion (P < 0.01) induced by AGEs or H2O2 in 3T3-L1
      preadipocytes. Both teas also inhibited the decline in the enzymatic activities
      of superoxide dismutase, catalase and glutathione peroxidase induced by the pro
      oxidants. The teas further suppressed the glycation of BSA mediated by glucose,
      ribose and MGO by reducing fluorescent AGE, fructosamine, protein carbonyl and
      AOPP levels. Black and green teas also inhibited the activities of alpha-amylase
      (AA50: 589.86 +/- 39.51 and 947.80 +/- 18.20 MUg mL-1, respectively) and alpha
      glucosidase (AA50: 72.31 +/- 4.23 and 100.23 +/- 8.10 MUg mL-1, respectively).
      The teas afforded a comparable level of protection at the cellular level and
      against glycation while black tea exerted the highest carbohydrate hydrolysing
      enzymes inhibitory activity. Our results clearly show that black and green teas
      represent an important source of antioxidants with anti-diabetic potential.

PMID- 29043350
TI  - Microfluidic diafiltration-on-chip using an integrated magnetic peristaltic
      micropump.
AB  - Diafiltration is a membrane filtration technique that rapidly removes permeable
      molecules from a solution by controlling the tangential and orthogonal flows over
      a membrane and by replenishing the permeate with an equivalent amount of
      replacement buffer. However, its application to the purification of many key
      biomaterials and nanomaterials has been limited by the large dead volume (>10 mL)
      that is required to automate the process. To address this challenge, we have
      developed a diafiltration-on-a-chip device that can process low-volume samples
      (50 MUL). The key innovation of this device is a magnetically-driven on-chip
      peristaltic pump that is able to continuously drive fluid flow at rates as high
      as 50 mL h-1 with minimal external instrumentation and a dead volume of <50 MUL.
      To demonstrate the utility of this device, we purified microbeads from dye with
      >99% purity and >96% retention within two hours. We additionally showed that
      cells could be purified from microbeads with >97% purity and >97% retention in
      two hours. Because our approach requires minimal instrumentation, it is well
      suited for on-chip parallelization, which was demonstrated by incorporating four
      complete diafiltration systems onto a single credit card-sized chip.

PMID- 29043351
TI  - CoSex nanocrystalline-dotted CoCo layered double hydroxide nanosheets: a
      synergetic engineering process for enhanced electrocatalytic water oxidation.
AB  - Manipulating the electrical conductivity and morphology of Co-based (hydr)oxides
      is significant for optimizing energy conversion in the oxygen evolution reaction
      (OER). Herein, 2D CoSex nanocrystalline-dotted porous CoCo layered double
      hydroxide nanosheets (Co-Se NSs) were designed and synthesized via a modified in
      situ reduction and interface-directed assembly in an inert atmosphere. During the
      synchronous reduction/precipitation reaction between Co2+-oleylamine and NaHSe at
      the toluene-water interface, the hydrated Co-O and Co-Se clusters are generated
      and sequentially assemble under strong extrusion driven by the interfacial
      tension. Owing to the enriched vacancies on the lateral surfaces, the obtained
      loose and porous Co-Se NS presents low crystallinity. Moreover, electrons could
      spontaneously transfer from the CoCo LDH to the neighboring CoSex
      nanocrystallites due to the stronger electron-withdrawing capability of metallic
      CoSex, and thus more Co atoms in the CoCo layered double hydroxide (LDH) present
      a high oxidation state. This synergistic manipulation in the structure,
      component, and electron configuration of the Co-Se NS can increase the density of
      the OER active-sites, improve the electrical conductivity, and also offer a large
      accessible surface area and permeable channels for ion adsorption and transport.
      As a result, the resulting Co-Se NSs feature high catalytic activity towards OER,
      in particular a low onset potential of 1.48 V and an overpotential of only 290 mV
      at a current density of 10 mA cm-2 for the Co-Se-2 NS, as well as good stability
      in an accelerated durability test. The strategy developed here provides a
      reliable and valid way to synthesize multicomponent NSs, and is able to be
      extended to other areas of application.

PMID- 29043353
TI  - Machine learnt bond order potential to model metal-organic (Co-C)
      heterostructures.
AB  - A fundamental understanding of the inter-relationships between structure,
      morphology, atomic scale dynamics, chemistry, and physical properties of mixed
      metallic-covalent systems is essential to design novel functional materials for
      applications in flexible nano-electronics, energy storage and catalysis. To
      achieve such knowledge, it is imperative to develop robust and computationally
      efficient atomistic models that describe atomic interactions accurately within a
      single framework. Here, we present a unified Tersoff-Brenner type bond order
      potential (BOP) for a Co-C system, trained against lattice parameters, cohesive
      energies, equation of state, and elastic constants of different crystalline
      phases of cobalt as well as orthorhombic Co2C derived from density functional
      theory (DFT) calculations. The independent BOP parameters are determined using a
      combination of supervised machine learning (genetic algorithms) and local
      minimization via the simplex method. Our newly developed BOP accurately describes
      the structural, thermodynamic, mechanical, and surface properties of both the
      elemental components as well as the carbide phases, in excellent accordance with
      DFT calculations and experiments. Using our machine-learnt BOP potential, we
      performed large-scale molecular dynamics simulations to investigate the effect of
      metal/carbon concentration on the structure and mechanical properties of porous
      architectures obtained via self-assembly of cobalt nanoparticles and fullerene
      molecules. Such porous structures have implications in flexible electronics,
      where materials with high electrical conductivity and low elastic stiffness are
      desired. Using unsupervised machine learning (clustering), we identify the pore
      structure, pore-distribution, and metallic conduction pathways in self-assembled
      structures at different C/Co ratios. We find that as the C/Co ratio increases,
      the connectivity between the Co nanoparticles becomes limited, likely resulting
      in low electrical conductivity; on the other hand, such C-rich hybrid structures
      are highly flexible (i.e., low stiffness). The BOP model developed in this work
      is a valuable tool to investigate atomic scale processes, structure-property
      relationships, and temperature/pressure response of Co-C systems, as well as
      design organic-inorganic hybrid structures with a desired set of properties.

PMID- 29043354
TI  - Lipidomic profiles of Drosophila melanogaster and cactophilic fly species: models
      of human metabolic diseases.
AB  - The metabolic syndrome (MetS) is associated with serious diseases and represents
      an important threat for global public health. The common fruit fly (Drosophila
      melanogaster) has served as a model organism to study physiological processes of
      the MetS, because central metabolic pathways are conserved among species, and
      because the flies are easy to cultivate in a laboratory. In nature, D.
      melanogaster is a fruit generalist, feeding on diets rich in simple
      carbohydrates. Other Drosophilids, however, have specialized on distinct
      resources. Drosophila mojavensis, for example, is endemic to the Sonoran Desert,
      where it feeds on necrotic cacti which are low in carbohydrates. Its close
      relative Drosophila arizonae is cactophilic as well, but is also found breeding
      in fruits containing simple sugars. Previous studies have shown that high-sugar
      diets negatively affect the larval development of D. mojavensis and increase
      their triglyceride content, compared to D. melanogaster. More general metabolic
      profiles, in response to these different diets, however, have yet to be produced
      for any of the species. In addition, because D. arizonae appears somewhat
      intermediate between D. melanogaster and D. mojavensis in its development times
      and survival under the above mentioned diets, its general metabolic profiles are
      also of interest. Thus, in the present study we ask to what extent the general
      metabolism of these three different Drosophila species is affected by diets of
      distinct protein-sugar ratios. To obtain an un-biased view on possibly novel
      phenomena, we combined untargeted metabolomics with Random Forest data mining.

PMID- 29043355
TI  - Double-grooved nanofibre surfaces with enhanced anisotropic hydrophobicity.
AB  - This study reports a facile method for fabricating double-grooved fibrous
      surfaces. The primary grooves of the surface are formed by aligned fibres, while
      the secondary grooves are achieved by oriented nanogrooves on the fibre surface.
      Investigation into the formation mechanism reveals that the nanogrooves can be
      readily tailored through adjusting the solvent ratio and relative humidity. With
      this understanding, a variety of polymers have been successfully electrospun into
      fibres having the same nanogrooved feature. These fibres show high resemblance to
      natural hierarchical structures, and thereby endowing the corresponding double
      grooved surface with enhanced anisotropic hydrophobicity. A water droplet at a
      parallel direction to the grooves exhibits a much higher contact angle and a
      lower roll-off angle than the droplet at a perpendicular direction. The
      application potential of such anisotropic hydrophobicity has been demonstrated
      via a fog collection experiment, in which the double-grooved surface can harvest
      the largest amount of water. Moreover, the fabrication method requires neither
      post-treatment nor sophisticated equipment, making us anticipate that the double
      grooved surface would be competitive in areas where a highly ordered surface, a
      large surface area and an anisotropic hydrophobicity are preferred.

PMID- 29043356
TI  - Cationic amphiphilic Zn-porphyrin with high antifungal photodynamic potency.
AB  - Photodynamic therapy (PDT) is a promising alternative approach particularly
      attractive for treatment of localized fungal infections. It is based on
      compounds, photosensitizers (PSs), which when excited with visible light,
      generate reactive species that ultimately cause cell death. Such species have
      short lifespans; as a consequence, efficiency and selectivity of the PDT
      treatment depend mainly on the properties of the PSs. This study is the first to
      explore the effect of cationic porphyrin-based photosensitizers on Saccharomyces
      cerevisiae, a member of the fungus kingdom. The study investigates which
      properties of the PS are essential for efficient antifungal PDT. Cationic Zn(ii)
      meso-tetrakis(N-alkylpyridinium-2-yl)porphyrins (ZnP) with identical tetrapyrrole
      core and photo-physical properties, but with different substituents at the meso
      positions of the porphyrin ring were studied. Attaching six-carbon aliphatic
      chains to the four pyridyl nitrogens at all meso positions to the porphyrin ring
      produced a highly photo-efficient amphiphilic, water soluble PS, with minimal
      dark toxicity. It was taken up by the yeast cells and upon illumination
      suppressed metabolism by inactivating cytoplasmic and mitochondrial enzymes, and
      compromising plasma membrane barrier function. At low concentrations (up to 5
      MUM) the tetrahexyl derivative was a much more powerful antifungal agent than the
      commercially available chlorin e6. The more lipophilic tetraoctyl analog was also
      highly photo-efficient but displayed strong dark toxicity, presumably due to
      higher lipophilicity which might affect the lipid bilayer of membranes. Results
      presented here can assist the design of antifungal agents whose biological action
      depends on efficient and rapid uptake by the cells.

PMID- 29043357
TI  - Localization of platinum nanoparticles on inner walls of mesoporous hollow carbon
      spheres for improvement of electrochemical stability.
AB  - Mesoporous hollow carbon spheres with Pt nanoparticles (NPs) loaded on their
      inner walls (Pt@HC-meso) have been designed and prepared through a dual
      templating method. The core-shell structured Pt/SiO2@micelle-polydopamine (PDA)
      precursor is obtained by first depositing Pt NPs on silica spheres and then
      coating them with the carbon precursor of PDA and diblock copolymer micelles as
      soft templates. The subsequent carbonization and KOH etching convert the micelle
      PDA shells into mesoporous carbon and remove the silica cores, respectively.
      Thus, the Pt NPs are subjected to calcination and left on the inner walls. The
      fabricated Pt@HC-meso achieved high electrocatalytic performance and outstanding
      stability in catalyzing methanol oxidation. We infer that the mesoporous carbon
      shells not only provide accessible diffusion pathways for the reactants, but also
      protect the inner Pt NPs from collision with Pt NPs in other hollow carbon
      spheres. Each hollow carbon sphere with Pt NPs inside can be regarded as an
      independent nanoreactor. Moreover, observations of the morphology have proved
      that the calcined Pt NPs avoid a second aggregation during the electrocatalytic
      process and maintain long-term stability.

PMID- 29043358
TI  - Efficient liposome fusion mediated by lipid-nucleic acid conjugates.
AB  - The fusion of biomembranes with release of encapsulated content in a controlled
      way is crucial for cell signaling, endo- and exocytosis and intracellular
      trafficking. Programmable fusion of liposomes and an efficient mixing of their
      contents have the potential to enable the study of chemical and enzymatic
      processes in a confined environment and under crowded conditions outside
      biological systems. We report on DNA-controlled fusion of lipid bilayer membranes
      using lipid-nucleic acid conjugates (LiNAs) to mediate lipid and content mixing
      of liposomes. Screening of different membrane anchor and linker structures as
      well as incubation temperatures led to significantly improved fusion and content
      mixing compared to reported systems. LiNA designs were optimized by changing
      lipophilic moieties as membrane anchors, PEG-spacer patterns and by introducing
      locked nucleic acid (LNA) modifications. Liposome fusion induced by complementary
      LiNAs results in remarkable efficient content mixing at 37  degrees C and 50 
      degrees C (up to 70%) with low leakage (<=5%).

PMID- 29043359
TI  - Selective recognition of quaternary ammonium ions and zwitterions by using a
      biomimetic bis-calix[6]arene-based receptor.
AB  - Artificial receptors able to recognize efficiently chemical species bearing a
      quaternary ammonium group have potential applications in the fields of biological
      and environmental analyses. A possible biomimetic strategy for the elaboration of
      such receptors consists of associating in close proximity a polyaromatic cavity
      with a polar binding site. Herein, we show that bis-calix[6]arene 1 behaves as a
      heteroditopic receptor that can bind biologically relevant quaternary ammonium
      ions and zwitterions. This host can selectively extract carbamylcholine G3 from
      water, opening the way for the sensing of this acetylcholine agonist. In some
      cases, a kinetic selectivity is observed for the shorter guests whereas
      kinetically stable host-guest complexes can be detected under conditions where
      they are thermodynamically disfavoured. These results can be rationalized by the
      unique mode of entrance and escape of the guests into bis-calix[6]arene 1. All
      these binding properties strongly differ from those reported for related
      calixarene-based receptors.

PMID- 29043360
TI  - Synthesis, photophysical and biological properties of a new oxazolone fluorescent
      probe for bioimaging: an experimental and theoretical study.
AB  - In this study, a new oxazolone derivative 4-{N,N-bis[2-phenyl-4-benzylidene-1,3
      oxazol-5(4H)-one]amino}benzaldehyde (PB3) was synthesized and investigated as a
      fluorescent dye. The spectroscopic properties in different solvents were
      thoroughly studied. The experimental data were supported by quantum-chemical
      calculations using density functional theory. Measurements and theoretical
      calculations showed that the PB3 dye is characterized by non-monotonic
      solvatochromism, a strongly polar charge transfer excited state, a large Stokes'
      shift, a high fluorescence quantum yield and a high fluorescence lifetime.
      Bioconjugate complexes (PB3-concanavalin A) were studied by circular dichroism
      (CD) spectroscopy. The results showed that the secondary structure of
      concanavalin A was not significantly influenced by the PB3-fluorophore.
      Conventional fluorescence microscopy imaging of Candida albicans cells, incubated
      with the PB3-concanavalin A, was demonstrated. The results from cytochemistry
      experiments demonstrate that the PB3 dye has valuable advantages compared to the
      other long-wavelength dyes in typical fluorescence-based cell labeling
      applications. In vitro tolerance was evaluated by the MTT method in the human
      colon adenocarcinoma cell line HT29. The PB3 and bioconjugate complexes (PB3
      concanavalin A), in the range of concentrations tested, were not considerably
      toxic. The AutoDock simulations showed LYS46 as the most likely active site for
      covalent bond formation during PB3-concanavalin A conjugation. In addition,
      theoretical studies have shown that PB3 is characterized by good bioavailability
      and absorption/transmission across the cell membrane. This molecule will not
      bioaccumulate in living organisms and should be excreted in urine without
      interacting with other drugs. This work provided promising results for the red
      fluorescent probe (PB3) as a valuable alternative to commercial probes designed
      for cellular labeling in biological and biomedical research.

PMID- 29043361
TI  - Ion transport in gel and gel-liquid systems for LiClO4-doped PMMA at the meso-
      and nanoscales.
AB  - Solid and gel electrolytes offer significant advantages for cycle stability and
      longevity in energy storage technologies. These advantages come with trade-offs
      such as reduced conductivity and ion mobility, which can impact power density in
      storage devices even at the nanoscale. Here we propose experiments aimed at
      exploring the ion transport properties of a hybrid electrolyte system of liquid
      and gel electrolytes with meso and nanoscale components. We focus on single pore
      systems featuring LiClO4-propylene carbonate and LiClO4-PMMA gel, which are model
      electrolytes for energy storage devices. We identified conditions at which the
      systems considered featured rectifying current-voltage curves, indicating a
      preferential direction of ion transport. The presented ion current rectification
      suggests different mechanisms arising from the unique hybrid system: (i) PMMA
      structure imposing selectivity in fully immersed systems and (ii) ionic
      selectivity linked to ion sourcing from media of different ionic mobility. These
      mechanisms were observed to interplay with ion transport properties linked to
      nanopore structure i.e. cylindrical and conical.

PMID- 29043363
TI  - Blocking probe as a potential tool for detection of single nucleotide DNA
      mutations: design and performance.
AB  - Developing strategies to detect single nucleotide DNA mutations associated with
      treatment decisions in cancer patients from liquid biopsies is a rapidly emerging
      area of personalized medicine that requires high specificity. Here we report how
      to design an easy enzyme-free approach that could create a platform for detection
      of L858R mutation of EGFR that is a predictive biomarker of tyrosine kinase
      treatment in many cancers. This approach includes the addition of blocking probes
      with the antisense ssDNA at different blocking positions and different
      concentrations such as to avoid re-annealing with the respective sense ssDNA. The
      successful blocking strategy was corroborated by fluorescence spectroscopy in
      solution using two distinct FRET pairs and quartz crystal microbalance with
      dissipation (QCM-D) measurements under comparable experimental conditions, as the
      hybridization rate-limiting step in both methods is the nucleation process. The
      efficiency of hybridization of each blocking probe was strongly dependent on its
      position particularly when the analyte possesses a secondary hairpin-structure.
      We tested the performance of blocking probes in combination with gold
      nanoparticles; the obtained results were in agreement with those of QCM-D. These
      findings could facilitate the development of better biosensors, especially those
      using probes containing secondary structure.

PMID- 29043364
TI  - The synthesis of planar chiral pseudo-gem aminophosphine pre-ligands based on
      [2.2]paracyclophane.
AB  - The synthesis of three planar chiral pseudo-gem disubstituted [2.2]paracyclophane
      derived P,N-pre-ligands is reported along with preliminary results of their
      activity in the amination of aryl bromides and chlorides. The pseudo-gem
      aminophosphines were capable of mediating the coupling reaction at a loading of 1
      mol%.

PMID- 29043365
TI  - The behavior of hydroxide and hydronium ions at the hexadecane-water interface
      studied with second harmonic generation and zeta potential measurements.
AB  - By probing the electric potential at the hexadecane-water interface with second
      harmonic generation and the zeta potential at the surface of a hexadecane droplet
      in its emulsion, we show that hydronium ions don't have a specific affinity to
      the oil-water interface although hydroxide ions do. The observed apparent
      affinity of the hydronium ions to the hexadecane-water interface is more likely a
      result of the electro-static attraction effect. The adsorption free energy of the
      hydroxide ions at the oil-water interface was estimated to be -8.3 kcal mol-1.
      This study provides more experimental evidence for understanding the behavior of
      hydronium and hydoxide ions at the oil-water interface.

PMID- 29043366
TI  - Distance dependent photoacoustics revealed through DNA nanostructures.
AB  - Molecular rulers that rely on the Forster resonance energy transfer (FRET)
      mechanism are widely used to investigate dynamic molecular processes that occur
      on the nanometer scale. However, the capabilities of these fluorescence molecular
      rulers are fundamentally limited to shallow imaging depths by light scattering in
      biological samples. Photoacoustic tomography (PAT) has recently emerged as a high
      resolution modality for in vivo imaging, coupling optical excitation with
      ultrasound detection. In this paper, we report the capability of PAT to probe
      distance-dependent FRET at centimeter depths. Using DNA nanotechnology we created
      several nanostructures with precisely positioned fluorophore-quencher pairs over
      a range of nanoscale separation distances. PAT of the DNA nanostructures showed
      distance-dependent photoacoustic signal enhancement and demonstrated the ability
      of PAT to reveal the FRET process deep within tissue mimicking phantoms. Further,
      we experimentally validated these DNA nanostructures as a novel and biocompatible
      strategy to augment the intrinsic photoacoustic signal generation capabilities of
      small molecule fluorescent dyes.

PMID- 29043367
TI  - Boron nitride nanotubes as a heat sinking and stress-relaxation layer for high
      performance light-emitting diodes.
AB  - High-density threading dislocations, the presence of biaxial compressive strain,
      and heat generation are the major limitations obstructing the performance and
      reliability of light emitting diodes (LEDs). Herein, we demonstrate a facile
      epitaxial lateral overgrowth (ELOG) method by incorporating boron nitride
      nanotubes (BNNTs) on a sapphire substrate by spray coating to resolve the above
      issues. Atomic force microscopy, X-ray diffraction, micro-Raman, and
      photoluminescence measurements confirmed the growth of a high quality GaN
      epilayer on the BNNT-coated sapphire substrate with reduced threading
      dislocations and compressive strain owing to the ELOG process. GaN LEDs
      fabricated using this approach showed a significant enhancement in the internal
      quantum efficiency and electroluminescence intensity compared to conventional
      LEDs grown on sapphire. Moreover, reduced efficiency droop and surface
      temperature at high injection currents were achieved due to the excellent thermal
      stability and conductivity of BNNTs. Based on our findings we infer that the
      BNNTs would be a promising material for high power devices vulnerable to self
      heating problems.

PMID- 29043368
TI  - Self-coacervation of modular squid beak proteins - a comparative study.
AB  - The beak of the Humboldt squid is a biocomposite material made solely of organic
      components - chitin and proteins - which exhibits 200-fold stiffness and hardness
      gradients from the soft base to the exceptionally hard tip (rostrum). The
      outstanding mechanical properties of the squid beak are achieved via controlled
      hydration and impregnation of the chitin-based scaffold by protein coacervates.
      Molecular-based understanding of these proteins is essential to mimic the natural
      beak material. Here, we present detailed studies of two histidine-rich beak
      proteins (HBP-1 and -2) that play central roles during beak bio-fabrication. We
      show that both proteins have the ability to self-coacervate, which is governed
      intrinsically by the sequence modularity of their C-terminus and extrinsically by
      pH and ionic strength. We demonstrate that HBPs possess dynamic structures in
      solution and achieve maximum folding in the coacervate state, and propose that
      their self-coacervation is driven by hydrophobic interactions following charge
      neutralization through salt-screening. Finally, we show that subtle differences
      in the modular repeats of HBPs result in significant changes in the rheological
      response of the coacervates. This knowledge may be exploited to design self
      coacervating polypeptides for a wide range of engineering and biomedical
      applications, for example bio-inspired composite materials, smart hydrogels and
      adhesives, and biomedical implants.

PMID- 29043369
TI  - Contrasting water adhesion strengths of hydrophobic surfaces engraved with
      hierarchical grooves: lotus leaf and rose petal effects.
AB  - The (de)wetting transitions of hierarchical grooves periodically engraved on a
      hydrophobic surface were investigated using a fully atomistic molecular dynamics
      simulation. The (meta) stable and transition states with sagging or depinning
      liquid surfaces were identified by calculating the free energy profiles of the
      (de)wetting transitions. The dewetting transitions for wide and narrow minor
      grooves have large and small activation free energies, respectively, exhibiting
      contrasting water adhesion forces as found for rose petals and lotus leaves.

PMID- 29043370
TI  - Enhanced efficiency and air-stability of NiOX-based perovskite solar cells via
      PCBM electron transport layer modification with Triton X-100.
AB  - We modified phenyl-C61-butyric acid methyl ester (PCBM) for use as a stable,
      efficient electron transport layer (ETL) in inverted perovskite solar cells
      (PSCs). PCBM containing a surfactant Triton X-100 acts as the ETL and NiOX
      nanocrystals act as a hole transport layer (HTL). Atomic force microscopy and
      scanning electron microscopy images showed that surfactant-modified PCBM (s-PCBM)
      forms a high-quality, uniform, and dense ETL on the rough perovskite layer. This
      layer effectively blocks holes and reduces interfacial recombination. Steady
      state photoluminescence and electrochemical impedance spectroscopy analyses
      confirmed that Triton X-100 improved the electron extraction performance of PCBM.
      When the s-PCBM ETL was used, the average power conversion efficiency increased
      from 10.76% to 15.68%. This improvement was primarily caused by the increases in
      the open-circuit voltage and fill factor. s-PCBM-based PSCs also showed good air
      stability, retaining 83.8% of their initial performance after 800 h under ambient
      conditions.

PMID- 29043371
TI  - Decoding glycan protein interactions by a new class of asymmetric N-glycans.
AB  - N-Glycans are normally involved in crucial physiological and disease processes by
      interactions with glycan-binding proteins. So far structurally defined N-glycans
      have been good candidates for glycan binding study. Herein, a class of
      homogeneous asymmetric N-glycans was synthesized by coupling glycan-oxazoline and
      N-glycans using EndoM N175Q catalyzed quick glycan extension. Branch-biased
      binding and spacial inhibition caused by the bulky group on the other branch of N
      glycan were observed in glycan protein interactions involving lectins and these
      glycans by glycan microarray study. These new compounds are valuable for
      functional glycomic studies to better understand new functions of glycans and
      glycan-binding proteins.

PMID- 29043372
TI  - Environmental noise and breast cancer risk?

PMID- 29043373
TI  - Correction to: Venoarterial extracorporeal membrane oxygenation for refractory
      cardiogenic shock post-cardiac arrest.
AB  - The second element of the first author's name was misinterpreted as a given name,
      whereas in fact it is part of his family name. The correct version of his name
      for indexing purposes is therefore M. Pineton de Chambrun (not M. P. de
      Chambrun).

PMID- 29043374
TI  - [Overactive bladder-which treatment when?]
AB  - The term OAB (overactive bladder) describes a symptom complex. Therefore, initial
      treatment should be based on clinical symptoms and the results of basic
      diagnostics. Patient preference is essential for the choice of the initial
      treatment. Behavioural therapy, electrostimulation and medical treatment are
      available treatment options. If these are not effective, extended diagnostic
      examinations should be performed prior to minimally invasive treatments, like
      onabotulinumtoxin injections in the detrusor or sacral neuromodulation. Surgical
      interventions like augmentation cystoplasty are rarely required today.

PMID- 29043375
TI  - Assessing the structure and meaningfulness of the dissociative subtype of PTSD.
AB  - PURPOSE: Studies conducted in the USA, Canada and Denmark have supported the
      existence of the dissociative PTSD subtype, characterized primarily by symptoms
      of depersonalization and derealization. The current study aimed to examine the
      dissociative PTSD subtype in an Eastern European, predominantly female (83.16%)
      sample, using an extended set of dissociative symptoms. METHODS: A latent profile
      analysis was applied to the PTSD and dissociation data from 689 trauma-exposed
      university students from Slovakia. RESULTS: Four latent profiles of varying PTSD
      and dissociation symptomatology were uncovered. They were named non-symptomatic,
      moderate PTSD, high PTSD and dissociative PTSD. The dissociative PTSD profile
      showed elevations on depersonalization and derealization, but also the
      alternative dissociative indicators of gaps in awareness and memory, sensory
      misperceptions and cognitive and behavioural re-experiencing. The core PTSD
      symptoms of 'memory impairment' and 'reckless or self-destructive behaviour' were
      also significantly elevated in the dissociative PTSD profile. Moreover, anxiety
      and anger predicted membership in the dissociative PTSD profile. CONCLUSION: The
      results provide support for the proposal that the dissociative PTSD subtype can
      be characterized by a variety of dissociative symptoms.

PMID- 29043376
TI  - Enhanced rhamnolipid production in Burkholderia thailandensis transposon knockout
      strains deficient in polyhydroxyalkanoate (PHA) synthesis.
AB  - Microbially produced rhamnolipids have significant commercial potential; however,
      the main bacterial producer, Pseudomonas aeruginosa, is an opportunistic human
      pathogen, which limits biotechnological exploitation. The non-pathogenic species
      Burkholderia thailandensis produces rhamnolipids; however, yield is relatively
      low. The aim of this study was to determine whether rhamnolipid production could
      be increased in Burkholderia thailandensis through mutation of genes responsible
      for the synthesis of the storage material polyhydroxyalkanoate (PHA), thereby
      increasing cellular resources for the production of rhamnolipids. Potential PHA
      target genes were identified in B. thailandensis through comparison with known
      function genes in Pseudomonas aeruginosa. Multiple knockout strains for the phbA,
      phbB and phbC genes were obtained and their growth characteristics and
      rhamnolipid and PHA production determined. The wild-type strain and an
      rhamnolipid (RL)-deficient strain were used as controls. Three knockout strains
      (DeltaphbA1, DeltaphbB1 and DeltaphbC1) with the best enhancement of rhamnolipid
      production were selected for detailed study. DeltaphbB1 produced the highest
      level of purified RL (3.78 g l-1) compared to the wild-type strain (1.28 g l-1).
      In DeltaphbB1, the proportion of mono-rhamnolipid was also increased compared to
      the wild-type strain. The production of PHA was reduced by at least 80% in all
      three phb mutant strains, although never completely eliminated. These results
      suggest that, in contrast to Pseudomonas aeruginosa, knockout of the PHA
      synthesis pathway in Burkholderia thailandensis could be used to increase
      rhamnolipid production. The evidence of residual PHA production in the phb mutant
      strains suggests B. thailandensis possesses a secondary unelucidated PHA
      synthesis pathway.

PMID- 29043377
TI  - [Lung cancer : What has been confirmed in therapy?]
AB  - Metastatic non-small cell lung cancer has now been subdivided into several
      subtypes. The five basic principles of treatment include chemotherapy, anti
      angiogenic therapy, targeted therapy, immunotherapy and early palliative care.
      The latter should be implemented for all patients with metastatic lung cancer.
      The use of the other modalities depends on the histological subtype, as well as
      on the immunohistochemical and molecular features of the tumor.

PMID- 29043378
TI  - [Neurogenic myopathies and imaging of muscle denervation].
AB  - CLINICAL ISSUE: Neurogenic myopathies are primary diseases of the nervous system,
      which secondarily result in denervation of the target musculature. The spectrum
      of potential causes is manifold ranging from acute traumatic injuries and chronic
      compression to neurodegenerative, inflammatory, metabolic and neoplastic
      processes. STANDARD DIAGNOSTIC METHODS: The medical history, clinical
      neurological examination, and electrophysiological tests including
      electromyography and nerve conduction studies are crucial in diagnosing
      neuropathic myopathies. Electromyography is the gold standard for diagnosing
      muscle denervation. METHODICAL INNOVATIONS: Additional imaging methods and
      magnetic resonance imaging (MRI) in particular, are capable of contributing
      valuable information. The MRI examination of denervated musculature shows edema,
      an increase in the apparent diffusion coefficient (ADC) and hyperperfusion.
      Chronic denervation results in fatty degeneration and atrophy of affected
      muscles, which are also detectable by MRI. PERFORMANCE: Although the MRI findings
      in muscle denervation are relatively unspecific, they show a high sensitivity,
      comparable to electromyography. Dedicated MR neurography may often visualize the
      underlying lesion(s) of the innervating nerve(s). ACHIEVEMENTS: Besides high
      sensitivity, comparable to electromyography, MRI is capable of evaluating muscles
      which are inaccessible for needle electromyography. Due to its non-invasive
      character, MRI is ideal for follow-up examinations. PRACTICAL RECOMMENDATIONS:
      The use of MRI is often a meaningful addition to the diagnostics of neurogenic
      myopathies. The extent and distribution pattern of muscular alterations often
      provide information on the localization of the causative nerve damage. A correct
      diagnosis or at least a narrowing down of possible differential diagnoses can
      often be achieved using MRI.

PMID- 29043380
TI  - Are We Underestimating Microplastic Contamination in Aquatic Environments?
AB  - Plastic debris, specifically microplastic in the aquatic environment, is an
      escalating environmental crisis. Efforts at national scales to reduce or ban
      microplastics in personal care products are starting to pay off, but this will
      not affect those materials already in the environment or those that result from
      unregulated products and materials. To better inform future microplastic research
      and mitigation efforts this study (1) evaluates methods currently used to
      quantify microplastics in the environment and (2) characterizes the concentration
      and size distribution of microplastics in a variety of products. In this study,
      50 published aquatic surveys were reviewed and they demonstrated that most (~80%)
      only account for plastics >= 300 MUm in diameter. In addition, we surveyed 770
      personal care products to determine the occurrence, concentration and size
      distribution of polyethylene microbeads. Particle concentrations ranged from 1.9
      to 71.9 mg g-1 of product or 1649 to 31,266 particles g-1 of product. The large
      majority ( > 95%) of particles in products surveyed were less than the 300 MUm
      minimum diameter, indicating that previous environmental surveys could be
      underestimating microplastic contamination. To account for smaller particles as
      well as microfibers from synthetic textiles, we strongly recommend that future
      surveys consider methods that materials < 300 MUm in diameter.

PMID- 29043379
TI  - Copy number variation and disease resistance in plants.
AB  - Plant genome diversity varies from single nucleotide polymorphisms to large-scale
      deletions, insertions, duplications, or re-arrangements. These re-arrangements of
      sequences resulting from duplication, gains or losses of DNA segments are termed
      copy number variations (CNVs). During the last decade, numerous studies have
      emphasized the importance of CNVs as a factor affecting human phenotype; in
      particular, CNVs have been associated with risks for several severe diseases. In
      plants, the exploration of the extent and role of CNVs in resistance against
      pathogens and pests is just beginning. Since CNVs are likely to be associated
      with disease resistance in plants, an understanding of the distribution of CNVs
      could assist in the identification of novel plant disease-resistance genes. In
      this paper, we review existing information about CNVs; their importance, role and
      function, as well as their association with disease resistance in plants.

PMID- 29043381
TI  - Transformed follicular lymphoma.
AB  - Follicular Lymphoma (FL) is the second most common type of non-Hodgkin lymphoma
      and is considered to be the prototype of indolent lymphomas. Histologic
      transformation into an aggressive lymphoma, which is expected to occur at a rate
      of 2 to 3% each year, is associated with rapid progression, treatment resistance,
      and poor prognosis. Recent modifications to the physiopathologic mechanism of
      transformed follicular lymphoma (t-FL) have been proposed, including genetic and
      epigenetic mechanisms as well as a role for the microenvironment. Although t-FL
      is considered a devastating complication, as it is associated with treatment
      refractory disease and a dismal outcome, recent data in the rituximab era have
      suggested that not only is the prognosis less severe than reported in the
      previous literature but the risk of transformation is also lower. Thus, this
      study aimed to review the most recent research on t-FL in an attempt to better
      understand the clinical meaning of transformation from FL to diffuse large B cell
      lymphoma (DLBCL) and the impact of current treatment strategies on the curability
      of this intriguing subentity of lymphoma.

PMID- 29043382
TI  - Cell transfer of information via miR-loaded exosomes: a biophysical approach.
AB  - A new communication route among cells was reported in recent years, via
      extracellular vesicles and their cargo. Exosomes in particular are attracting
      increasing interest as privileged mediators of this cell communication route. The
      exosome-mediated transfer of nucleic acids, especially of microRNAs, is
      particularly promising for their use both as biomarkers of pathologies and as a
      therapeutic tool. Here, a simplified model of interaction among cells, microRNAs
      and vesicles is studied using a biophysical approach. A synthetic and fluorescent
      microRNA (i.e. miR-1246 conjugated with TAMRA) was selected to model cell
      communication, monitoring its internalization in cells. The fluorescent miR-1246,
      either naked or included in synthetic or natural vesicles, was incubated with
      human breast adenocarcinoma cells (MCF7) for different times. A comparison
      between this human microRNA and its DNA copy or an exogenous microRNA (from
      Caenorhabditis elegans) allowed assessment of the specificity of the information
      transfer through microRNAs, and especially associated with exosomes. The uptake
      of naked miR-1246 was indeed higher both in terms of number of targeted cells and
      intensity of fluorescence signal with respect to the other nucleic acids tested.
      The same occurred with miR-1246 loaded exosomes, evidencing a specific uptake
      only partially due to the lipidic components and present only when the human
      microRNA was loaded in exosomes, which were themselves derived from the same MCF7
      cells.

PMID- 29043384
TI  - Reply to the Letter: "Acute Carotid Artery Stent Thrombosis".

PMID- 29043383
TI  - Determination of heme in microorganisms using HPLC-MS/MS and cobalt(III)
      protoporphyrin IX inhibition of heme acquisition in Escherichia coli.
AB  - One of the main threats to the achievements in modern medicine is antimicrobial
      resistance. Molecular targeting of bacterial acquisition mechanisms of heme has
      been suggested to be an alternative to antibiotics. In the present study, HPLC
      MS/MS combined with a simple clean-up based on liquid-liquid extraction has been
      developed and evaluated for simultaneous determination of heme and porphyrin heme
      precursors in microorganisms. Experimental design was used to optimize the
      extraction parameters, to obtain a method with high recovery, low matrix effects,
      and high precision. The effects of additives in the culture medium on the
      biosynthesis of heme were studied using Escherichia coli as a model
      microorganism. 5-Aminolaevulinic acid and hemin increased the heme concentration
      in E. coli by a factor of 1.5 and 4.5, respectively. Addition of 5
      aminolaevulinic acid bypassed the E. coli negative feedback control of heme
      biosynthesis, which led to high amounts of intracellular porphyrins. The high
      heme concentration obtained when hemin was used as a culture additive shows that
      E. coli has an uptake of heme from its surroundings. In contrast, addition of
      cobalt protoporphyrin IX to the growth medium reduced the amount of heme in E.
      coli, demonstrating this compound's ability to mimic real heme and inhibit the
      heme acquisition mechanisms.

PMID- 29043385
TI  - Whole-Gland Prostate Cancer Cryoablation with Magnetic Resonance Imaging
      Guidance: One-Year Follow-Up.
AB  - PURPOSE: Patients who develop prostate cancer after prior abdominal perineal
      resection are poor surgical candidates, and have limited treatment options.
      Therefore, our goal is to present results from a single institutional experience
      of four patients who underwent whole gland MRI-guided cryoablation with a history
      complicated by prior abdominoperineal resection. MATERIALS AND METHODS: Four MRI
      guided cryoablative treatments (mean age 64, range 59-69 years) for primary and
      locally recurrent prostate adenocarcinoma were retrospectively reviewed in
      patients with prior abdominal perineal resection for colorectal cancer (3) and
      juvenile polyposis (1). Average prostate volume prior to ablation was 23 cc, with
      an average PSA of 5.6 ng/mL. For each gland, 7-10 cryoprobes were placed
      approximately 0.5 cm apart in the prostate gland under MRI guidance by a
      transperineal approach with 3-4 freeze-thaw cycles performed. Each patient had
      follow up imaging and PSA measurements out to 12 months post ablation. RESULTS:
      All four patient's PSA dropped below 0.1 ng/mL at 3-6 month post-ablation and
      remained at these levels at 12 months. Three of the 4 patients had PSA
      measurements to 33 months post-ablation, with no evidence of recurrence. No
      patient developed urinary incontinence due to the whole gland cryoablation.
      CONCLUSION: With all four patients in our study having undetectable PSAs 12
      months post ablation, and with no patient developing urinary incontinence due to
      the cryoablation, MRI-guided cryoablation appears to be a promising treatment
      option in patients who are poor surgical candidates due to prior pelvic surgery
      and/or radiation.

PMID- 29043386
TI  - Use of a Re-entry Device in Left Subclavian Occlusion: Case Series.
AB  - PURPOSE: To describe the use of a re-entry catheter in the endovascular treatment
      of left subclavian stenosis. MATERIALS AND METHODS: We present three patients
      where initial attempts at re-vascularisation using standard techniques were
      unsuccessful. An OUTBACK catheter was employed to facilitate re-entry in these
      patients. RESULTS: True lumen re-entry was achieved in all patients, leading to
      successful treatment of all stenoses. There was a lack of filling of the left
      vertebral artery post-angioplasty in one patient; this was not clinically
      significant. CONCLUSION: The case series presented is encouraging for the use of
      a re-entry catheter in the treatment of subclavian occlusion. In our limited
      experience this has proved to be a safe technique for use in patients who fail re
      vascularisation by standard methods; a larger study is required to confirm this.

PMID- 29043387
TI  - CYP3A genotypes of donors but not those of the patients increase the risk of
      acute rejection in renal transplant recipients on calcineurin inhibitors: a pilot
      study.
AB  - PURPOSE: We aimed to determine whether polymorphisms in CYP3A genes may affect
      the risk of acute rejection episodes (ARE) in renal transplant recipients treated
      with calcineurin inhibitors (CNIs). METHODS: One hundred and thirty seven
      patients and their respective donors were screened, by RT-PCR techniques, for
      three polymorphisms previously related with CNI pharmacokinetics and
      pharmacodynamics (CYP3A4*1B, CYP3A4*22 and CYP3A5*3). Genotypes of donors and
      recipients were associated by logistic regression models with ARE risk and
      exposure to CNIs. Clinical and pharmacokinetic parameters were recorded at four
      time-points after transplant (1 week and 1, 5 and 12 months). RESULTS: Nineteen
      patients (13.86%) experienced ARE. Patients who received a kidney from a donor
      carrying the CYP3A4*1B or CYP3A5*1 variant experienced ARE more frequently than
      those whose donor carried wild-type genotypes [OR = 6.29 (1.62-24.39), p = 0.008
      and OR = 3.42 (1.06-11.01), p = 0.039, respectively]. The combined analysis of
      the CYP3A4*1B/3A5*1 alleles also revealed an increased risk in patients whose
      donors carried both variants [OR = 6.24 (1.60-24.33), p = 0.007]. The CYP3A
      genotype of the recipient did not affect ARE risk, although it did determine the
      degree of exposure to CNI throughout the first year after transplant. Patients
      with one or two variant alleles displayed lower concentration-to-dose ratios
      (CDRs) than non-carriers, with differences increasing with time after transplant
      (p values = 0.039, 0.004, 6.0 e-04 and 2.7 e-07 in the four time-points).
      CONCLUSIONS: Our preliminary findings suggest that the determination of the CYP3A
      genotype of the donor, but not that of the recipient, may be useful to predict
      the incidence of acute rejection in renal transplantation.

PMID- 29043389
TI  - Biomagnification of Mercury in Fish from Two Gold Mining-Impacted Tropical
      Marshes in Northern Colombia.
AB  - Total mercury concentrations (T-Hg) and stable isotope ratios (delta15N and
      delta13C) were analyzed in the muscle of fish, collected at two marshes impacted
      by gold mining in Northern Colombia, to evaluate the seasonal and spatial
      behavior of these variables and mercury biomagnification based on their
      relationship with delta15N ratios in the fish. There was not significant (p >
      0.05) seasonal differences (dry and rainy season) in delta15N and delta13C values
      in none marsh, suggesting that these fish species keep a similar feed pattern
      within each marsh along the year. However, there were significant differences (p
      < 0.05) between marshes in delta15N, delta13C, and T-Hg, as well as significant
      seasonal differences (p < 0.05) in T-Hg values for some species, suggesting the
      possible influence of factors, such as differences in length of food chains
      between marshes and different degree of anthropogenic impact in relation to human
      settlements, farmland, livestock (higher in Ayapel marsh), and gold mining
      activity (higher in La Raya marsh). Correlations analysis showed significant (p <
      0.05) relationships between T-Hg concentrations and delta15N values, as well as
      trophic level, evidencing a T-Hg biomagnification process in the fish food chain
      from both marshes and consequently a potential health risk for human riverside
      inhabitants who eat these fish.

PMID- 29043388
TI  - Isolation and Potential Biocementation of Calcite Precipitation Inducing Bacteria
      from Colombian Buildings.
AB  - Microbiological induced calcium carbonate or calcite precipitation (MICP) has
      become a highly researched issue due to its multiple applications in the
      construction industry, being a promising alternative with a great
      biotechnological importance. In this work, potential calcite precipitation
      inducing bacteria were isolated from mortar and concrete samples of different
      buildings at the National University of Colombia. Eighteen crystal-precipitating
      strains were recovered in Urea-CaCl2 solid medium. The 16S rRNA gene sequencing
      identified isolates as Arthrobacter, Psychrobacillus and Rhodococcus genera. It
      is reported, for the first time, the calcite precipitation by P. psycrodurans and
      R. qingshengii. Optical microscopy and Scanning Electron Microscopy showed
      crystals with irregular and spherical shapes, and beige and white colours.
      Furthermore, crystals formation appeared to be strain-specific. X-Ray diffraction
      analysis confirmed crystals composition as CaCO3. Biocementation tests showed
      that MICP treatments of mortar cubes using P. psycrodurans caused an increase in
      their compressive strength compared to control samples. The positive action of a
      native MICP strain in mortar blocks biomineralization is shown, which is of great
      interest and potential for the construction industry.

PMID- 29043390
TI  - p-Nitrophenyl Acetate Esterase Activity and Cortisol as Biomarkers of Metal
      Pollution in Blood of Olive Ridley Turtles (Lepidochelys olivacea).
AB  - This study was designed to determine the concentrations of p-nitrophenyl acetate
      esterase activity (EA) and cortisol in serum of marine Olive Ridley turtles
      (Lepidochelys olivacea) from a Mexican Pacific population ("La Escobilla" beach)
      and to evaluate the possible relationship of inorganic elements with these
      biomarkers. EA, cortisol, and selected chemical elements (Cd, Pb, Ti, Sr, Se, Al,
      As, and Zn) were measured in the blood of 44 sea turtles from the Eastern Pacific
      (Southeast Mexico). Serum EA ranged from 0.4 to 3.9 UI mL-1, and cortisol
      concentrations ranged from 0.07 to 2.5 MUL dL-1. A strong negative correlation
      between EA and cortisol was observed (r = - 0.59, p < 0.01), and significant
      correlations also were found between EA and important metals, such as Cd (r = -
      0.31, p < 0.05) and Pb (r = - 0.27, p < 0.05), and elements of growing concern
      like Ti (r = - 0.37, p < 0.01) or Al (r = - 0.34, p < 0.05) and between cortisol
      and Sr (r = 0.29, p < 0.05), Se (r = - 0.38, p < 0.01), and As (r = - 0.26, p <
      0.05). These results suggest that turtles chronically exposed to different
      inorganic elements (such as Pb and Cd), driving to a highly consume of esterase
      and to a prolonged cortisol elevation. The obtained results indicate the
      usefulness of these biomarkers in the assessment of inorganic elements pollution
      in this species.

PMID- 29043391
TI  - Analysis of the evolution of cortical and trabecular bone compartments in the
      proximal femur after spinal cord injury by 3D-DXA.
AB  - : Marked trabecular and cortical bone loss was observed at the proximal femur
      short-term after spinal cord injury (SCI). 3D-DXA provided measurement of vBMD
      evolution at both femoral compartments and cortical thinning, thereby suggesting
      that this technique could be useful for bone analysis in these patients.
      INTRODUCTION: SCI is associated with a marked increase in bone loss and risk of
      osteoporosis development short-term after injury. 3D-DXA is a new imaging
      analysis technique providing 3D analysis of the cortical and trabecular bone from
      DXA scans. The aim of this study was to assess the evolution of trabecular
      macrostructure and cortical bone using 3D-DXA in patients with recent SCI
      followed over 12 months. METHODS: Sixteen males with recent SCI (< 3 months since
      injury) and without antiosteoporotic treatment were included. Clinical
      assessment, bone mineral density (BMD) measurements by DXA, and 3D-DXA evaluation
      at proximal femur (analyzing the integral, trabecular and cortical volumetric BMD
      [vBMD] and cortical thickness) were performed at baseline and at 6 and 12 months
      of follow-up. RESULTS: vBMD significantly decreased at integral, trabecular, and
      cortical compartments at 6 months (- 8.8, - 11.6, and - 2.4%), with a further
      decrease at 12 months, resulting in an overall decrease of - 16.6, - 21.9, and -
      5.0%, respectively. Cortical thickness also decreased at 6 and 12 months (- 8.0
      and - 11.4%), with the maximal decrease being observed during the first 6 months.
      The mean BMD losses by DXA at femoral neck and total femur were - 17.7 and -
      21.1%, at 12 months, respectively. CONCLUSIONS: Marked trabecular and cortical
      bone loss was observed at the proximal femur short-term after SCI. 3D-DXA
      measured vBMD evolution at both femoral compartments and cortical thinning,
      providing better knowledge of their differential contributory role to bone
      strength and probably of the effect of therapy in these patients.

PMID- 29043392
TI  - Complex interventions can increase osteoporosis investigations and treatment: a
      systematic review and meta-analysis.
AB  - Osteoporosis is affecting over 200 million people worldwide. Despite available
      guidelines, care for these patients remains sub-optimal. We developed an
      osteoporosis tool to address the multiple dimensions of chronic disease
      management. Findings from its evaluation showed a significant increase from
      baseline in osteoporosis investigations and treatment, so we are revising this
      tool to include multiple chronic conditions including an update of evidence about
      osteoporosis. Our objectives were to conduct a systematic review of osteoporosis
      interventions in adults at risk for osteoporosis. We searched bibliometric
      databases for randomized controlled trials (RCTs) in any language evaluating
      osteoporosis disease management interventions in adults at risk for osteoporosis.
      Reviewer pairs independently screened citations and full-text articles, extracted
      data, and assessed risk of bias. Analysis included random effects meta-analysis.
      Primary outcomes were osteoporosis investigations and treatment, and fragility
      fractures. Fifty-five RCTs and one companion report were included in the analysis
      representing 165,703 patients. Our findings from 55 RCTs and 18 sub-group meta
      analyses showed that complex implementation interventions with multiple
      components consisting of at least education + feedback + follow-up significantly
      increased the initiation of osteoporosis medications, and interventions with at
      least education + follow-up significantly increased the initiation of
      osteoporosis investigations. No significant impact was found for any type of
      intervention to reduce fracture. Complex interventions that include at least
      education + follow-up or feedback have the most potential for increasing
      osteoporosis investigations and treatment. Patient education appears to be an
      important component in osteoporosis disease management.

PMID- 29043393
TI  - Characterization of a set of abdominal neuroendocrine cells that regulate stress
      physiology using colocalized diuretic peptides in Drosophila.
AB  - Multiple neuropeptides are known to regulate water and ion balance in Drosophila
      melanogaster. Several of these peptides also have other functions in physiology
      and behavior. Examples are corticotropin-releasing factor-like diuretic hormone
      (diuretic hormone 44; DH44) and leucokinin (LK), both of which induce fluid
      secretion by Malpighian tubules (MTs), but also regulate stress responses,
      feeding, circadian activity and other behaviors. Here, we investigated the
      functional relations between the LK and DH44 signaling systems. DH44 and LK
      peptides are only colocalized in a set of abdominal neurosecretory cells (ABLKs).
      Targeted knockdown of each of these peptides in ABLKs leads to increased
      resistance to desiccation, starvation and ionic stress. Food ingestion is
      diminished by knockdown of DH44, but not LK, and water retention is increased by
      LK knockdown only. Thus, the two colocalized peptides display similar systemic
      actions, but differ with respect to regulation of feeding and body water
      retention. We also demonstrated that DH44 and LK have additive effects on fluid
      secretion by MTs. It is likely that the colocalized peptides are coreleased from
      ABLKs into the circulation and act on the tubules where they target different
      cell types and signaling systems to regulate diuresis and stress tolerance.
      Additional targets seem to be specific for each of the two peptides and subserve
      regulation of feeding and water retention. Our data suggest that the ABLKs and
      hormonal actions are sufficient for many of the known DH44 and LK functions, and
      that the remaining neurons in the CNS play other functional roles.

PMID- 29043394
TI  - In Silico Analyses Reveal the Relationship Between SIX1/EYA1 Mutations and
      Conotruncal Heart Defects.
AB  - Conotruncal heart defects (CTDs) represent a group of severe and complicated
      congenital cardiovascular malformations and require opportune clinical
      interventions once diagnosed. Occurrence of CTD is related to the functional
      abnormality of the second heart field (SHF), and variants of genes which regulate
      the development of the second heart field have been recognized as the main
      genetic factors leading to CTDs. Previous studies indicated that transcriptional
      complex SIX1/EYA1 may contribute to SHF development, and SIX1/EYA1 knockout mice
      exhibited a series of conotruncal malformations. Here, we recruited and sequenced
      600 Chinese conotruncal heart defect patients and 300 controls. We screened out
      one novel SIX1 mutation (SIX1-K134R) and four EYA1 rare mutations (EYA1-A227T,
      EYA1-R296H, EYA1-Q397R, EYA1-G426S), all variants were present only in the case
      cohort, and the mutated sites were highly conserved. We then analyzed mutations
      by software including Sift, PolyPhen-2, PROVEAN, Mutation Taster, HOPE, and SWISS
      PdbViewer. The results showed that the mutations had varying degrees of
      pathogenic risk, protein properties, spatial conformations, and domain functions
      which might be altered or influenced. Through biological and in silico analyses,
      our study suggests an association between SIX1/EYA1 mutations and cardiovascular
      malformations, SIX1/EYA1 mutations might be partially responsible for CTDs.

PMID- 29043395
TI  - Measuring Flow Hemodynamic Indices and Oxygen Consumption in Children with
      Pulmonary Hypertension: A Comparison of Catheterization and Phase-Contrast MRI.
AB  - We sought to compare pulmonary flow hemodynamic indices obtained by Fick and
      thermodilution catheterization techniques with phase-contrast MRI (PC-MRI) in
      children with diverse etiologies of pulmonary arterial hypertension (PAH).
      Calculation of pulmonary flow ([Formula: see text]) using the Fick principle in
      most catheter laboratories relies on an estimate of oxygen consumption which may
      limit its reliability. Flow hemodynamic indices acquired from thirty patients
      with PAH who underwent successful same-day PC-MRI and catheterization were
      evaluated for absolute and percent bias. Comparison of [Formula: see text]
      between PC-MRI and Fick revealed poor agreement with an absolute bias of 0.96 +/-
      0.53 L/min/m2 and percent bias of 27.7 +/- 19.6%. Same analysis between PC-MRI
      and thermodilution revealed better agreement as demonstrated by absolute bias
      0.64 +/- 0.47 L/min/m2 and percent bias 16.8 +/- 12.3%. Retrospectively
      calculated [Formula: see text] from PC-MRI and LaFarge equations revealed poor
      agreement, with an absolute bias of 33.4 +/- 21.6 mL/min/m2 and percent bias of
      25.8 +/- 12.6%. We found that Fick-derived flow hemodynamics dramatically differs
      from PC-MRI computed metrics in children with PAH. The non-invasive nature of PC
      MRI and short acquisition time is ideal for pediatric flow evaluation and may
      offer a novel route of absolute flow and resistance assessment when combined with
      cardiac catheterization.

PMID- 29043397
TI  - Myocardial Fistulisation and Coronary Arterial Ectasia in Children with
      Univentricular Circulation: An Under-Recognised Problem.
AB  - Among 241 children with univentricular circulation who underwent total
      cavopulmonary connection (Glenn or Fontan) over a 17 years period (January 2000
      April 2017), we found two patients who had diffuse coronary fistulisation of
      their myocardium (0.8%). We also report an additional third case from Oak Lawn,
      Illinois, USA. One of the children had documented normal coronary arteries and
      myocardium at catheterisation prior to development of the fistulisation process.
      The same child also developed extensive veno-venous collaterals. All children had
      evidence of elevated pulmonary arterial pressures and were treated with a
      combination of pulmonary vasodilators. The presence of chronic hypoxaemia and
      elevated filling pressures could potentially have contributed to coronary
      endothelial dysfunction, thereby giving rise to the coronary vasculopathy and
      myocardial fistulisation. Alternatively, this myocardial fistulisation process
      may be present from early in life and not recognised. This may necessitate early
      referral for orthotopic cardiac transplantation. Diffuse fistulisation of the
      myocardium in children and young adults with univentricular circulation may be an
      under-recognised occurrence and coronary angiography should be considered in
      these patients.

PMID- 29043398
TI  - Oral Paracetamol for Patent Ductus Arteriosus Rescue Closure.
AB  - The objective of this study was to ascertain the efficacy of oral paracetamol in
      closing a symptomatic patent ductus arteriosus (PDA) when used as 'rescue'
      option. After obtaining ethics approval, a retrospective appraisal of the data
      from April 2014 to July 2015 was performed. Infants who were administered oral
      paracetamol either after unsuccessful therapy with ibuprofen or where it was
      considered contraindicated were included. A previously published
      echocardiographic scoring schema to stratify for ductal disease severity was
      used. Using univariate analysis, characteristics of infants with successful
      closure were compared with partial (a priori reduction in composite score by >=
      50% of pretreatment) or no closure. Twenty infants with gestation age and
      birthweight of 25.7 +/- 1.5 weeks and 724.1 +/- 143 g, respectively, were
      studied. Complete closure was noted in 10 (50%) infants with additional four
      infants showing a significant reduction in haemodynamic shunting. Gestational age
      at birth and at therapy, chronological age at therapy, birthweight and total
      fluid intake were comparable between the two groups. The pre-therapy composite
      score had a significant association with successful closure (the higher the
      echocardiographic score, the lesser the closure). Concomitant furosemide therapy
      and late-onset sepsis had a high likelihood ratio of unsuccessful closure (11.01
      [2-tailed, p = 0.005] and 5.3 [2-tailed, p = 0.07]), respectively. Oral
      paracetamol may be a possible therapeutic option in premature infants where
      therapy with first-line agents is unsuccessful or contraindicated. Concomitant
      sepsis and furosemide administration may affect successful therapy.

PMID- 29043396
TI  - Hypertension in Coarctation of the Aorta: Challenges in Diagnosis in Children.
AB  - Evidence indicates that patients with coarctation of the aorta (COA) suffer from
      increased cardiovascular morbidity and mortality in later life despite successful
      repair of COA in childhood. Systolic arterial hypertension is common, presenting
      in up to one-third of patients, and is regarded as the main driver of premature
      cardiovascular events in this group of patients. In this review, we discuss the
      prevalence and pathophysiology of hypertension in children following successful
      COA repair with no residual arch obstruction. The challenges in accurate blood
      pressure assessment at this early phase are considered and non-invasive measures
      of central blood pressure are discussed. Although the pathways for investigations
      in adults are well defined, we highlight the need to address the issues of
      cardiovascular surveillance in children and describe techniques which can provide
      complementary information for cardiovascular assessment in this group of patients
      such that timely treatment can occur.

PMID- 29043399
TI  - Immunohistochemical evaluation of molecular radiotherapy target expression in
      neuroblastoma tissue.
AB  - PURPOSE: Neuroblastoma may be treated with molecular radiotherapy, 131I meta
      Iodobenzylguanidine and 177Lu Lutetium DOTATATE, directed at distinct molecular
      targets: Noradrenaline Transporter Molecule (NAT) and Somatostatin Receptor
      (SSTR2), respectively. This study used immunohistochemistry to evaluate target
      expression in archival neuroblastoma tissue, to determine whether it might
      facilitate clinical use of molecular radiotherapy. METHODS: Tissue bank samples
      of formalin fixed paraffin embedded neuroblastoma tissue from patients for whom
      clinical outcome data were available were sectioned and stained with haematoxylin
      and eosin, and monoclonal antibodies directed against NAT and SSTR2. Sections
      were examined blinded to clinical information and scored for the percentage and
      intensity of tumour cells stained. These data were analysed in conjunction with
      clinical data. RESULTS: Tissue from 75 patients was examined. Target expression
      scores varied widely between patients: NAT median 45%, inter-quartile range 25% -
      65%; and SSTR2 median 55%, interquartile range 30% - 80%; and in some cases
      heterogeneity of expression between different parts of a tumour was observed. A
      weak positive correlation was observed between the expression scores of the
      different targets: correlation coefficient = 0.23, p = 0.05. MYCN amplified
      tumours had lower SSTR2 scores: mean difference 23% confidence interval 8% - 39%,
      p < 0.01. Survival did not differ by scores. CONCLUSIONS: As expression of both
      targets is variable and heterogeneous, imaging assessment of both may yield more
      clinical information than either alone. The clinical value of immunohistochemical
      assessment of target expression requires prospective evaluation. Variable target
      expression within a patient may contribute to treatment failure.

PMID- 29043401
TI  - The lambda (twin peak) sign.

PMID- 29043402
TI  - Imaging characterization of adnexal lesions: Do CT findings correlate with US?
AB  - OBJECTIVE: To compare contrast-enhanced CT and US agreement in characterizing
      adnexal lesions in late post-menopausal women. MATERIALS AND METHODS: This was a
      HIPAA-compliant IRB-approved retrospective review of the contrast-enhanced CTs of
      130 late post-menopausal women (> 55 years). The lesions were classified as
      simple cystic, minimally complex cystic, complex cystic, solid-cystic, or solid
      based on CT and US morphology. Findings were analyzed to evaluate agreement
      between CT and US on adnexal lesion characterization. RESULTS: One forty-one
      adnexal lesions were assessed by both contrast-enhanced CT and US. Overall, there
      was good agreement between CT and US, which agreed on the lesion morphology in
      114 (81%) cases with an unweighted kappa value of 0.68 (95% CI 0.56-0.78). By CT,
      83 (59%) were classified as simple cystic, of which 73/83 (88%) were confirmed as
      simple cystic by US. Of the remaining 10 CT simple cysts, 9 were reclassified by
      US as minimally complex cystic and one as complex cystic. Eight of these lesions
      were benign based on pathology or follow-up imaging, while two lesions remained
      indeterminate. By CT, 27 lesions (19%) were classified as minimally complex,
      while US reclassified 13 (48%) of the lesions (eight to simple cystic and five as
      complex or solid-cystic). Among the 31 remaining lesions, there were 4 (13%)
      discordances between CT and US. CONCLUSION: There is good agreement between CT
      and US in characterizing adnexal lesion morphology, particularly simple cysts.
      However, there was significant discordance seen with characterization of
      minimally complex cysts, indicating that these lesions need US follow-up.

PMID- 29043400
TI  - Static and dynamic 18F-FET PET for the characterization of gliomas defined by IDH
      and 1p/19q status.
AB  - PURPOSE: The molecular features isocitrate dehydrogenase (IDH) mutation and
      1p/19q co-deletion have gained major importance for both glioma typing and
      prognosis and have, therefore, been integrated in the World Health Organization
      (WHO) classification in 2016. The aim of this study was to characterize static
      and dynamic O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET parameters in gliomas
      with or without IDH mutation or 1p/19q co-deletion. METHODS: Ninety patients with
      newly diagnosed and untreated gliomas with a static and dynamic 18F-FET PET scan
      prior to evaluation of tumor tissue according to the 2016 WHO classification were
      identified retrospectively. Mean and maximum tumor-to-brain ratios (TBRmean/max),
      as well as dynamic parameters (time-to-peak and slope) of 18F-FET uptake were
      calculated. RESULTS: Sixteen (18%) oligodendrogliomas (IDH mutated, 1p/19q co
      deleted), 27 (30%) astrocytomas (IDH mutated only), and 47 (52%) glioblastomas
      (IDH wild type only) were identified. TBRmean, TBRmax, TTP and slope
      discriminated between IDH mutated astrocytomas and IDH wild type glioblastomas (P
      < 0.01). TBRmean showed the best diagnostic performance (cut-off 1.95;
      sensitivity, 89%; specificity, 67%; accuracy, 81%). None of the parameters
      discriminated between oligodendrogliomas (IDH mutated, 1p/19q co-deleted) and
      glioblastomas or astrocytomas. Furthermore, TBRmean, TBRmax, TTP, and slope
      discriminated between gliomas with and without IDH mutation (p < 0.01). The best
      diagnostic performance was obtained for the combination of TTP with TBRmax or
      slope (accuracy, 73%). CONCLUSION: Data suggest that static and dynamic 18F-FET
      PET parameters may allow determining non-invasively the IDH mutation status.
      However, IDH mutated and 1p/19q co-deleted oligodendrogliomas cannot be
      differentiated from glioblastomas and astrocytomas by 18F-FET PET.

PMID- 29043403
TI  - Hepatic morphology abnormalities: beyond cirrhosis.
AB  - The diagnosis of cirrhosis can be reached on the basis of established hepatic
      morphological changes. However, some other conditions can mimic cirrhosis. The
      aim of this pictorial essay is to review the CT and MRI appearances of hepatic
      morphology abnormalities in the cirrhotic liver and other diseases, describing
      pathologic conditions that can mimic cirrhosis, with useful tips for the
      differential diagnosis. Mimickers of cirrhosis include congenital hepatic
      fibrosis, Caroli disease, Budd-Chiari Syndrome, hepatoportal sclerosis, cavernous
      transformation of the portal vein, pseudocirrhosis from metastatic disease, acute
      liver failure, post-therapeutic morphologic changes in the liver, and infective
      conditions including schistosomiasis and oriental cholangiohepatitis. Recognizing
      the hepatic morphological changes in images can help radiologists to diagnose
      cirrhosis and other diseases in early stages.

PMID- 29043404
TI  - Epiploic appendagitis: 7-year experience and relationship with visceral obesity.
AB  - PURPOSE: Location, size, and local inflammatory findings in primary epiploic
      appendagitis (EA) have not been reported outside of small studies. The
      association between EA and increased adiposity is controversial. The goals of
      this project are to compare demographics and imaging-based measurements of
      adiposity between patients with EA and patients with acute abdomen without EA,
      and to identify CT features of EA. METHODS: A consecutive sample of acute,
      primary EA (n = 100), and control (acute abdomen; n = 100) was selected
      retrospectively. Cases of suspected EA were included if they had the
      characteristic ovoid fatty mass and hyperattenuated ring sign on CT. Abdominal
      adipose volume (AAV), visceral adipose area (VAA), and subcutaneous adipose area
      (SAA) were quantified by CT. Location, size, and frequency of coexisting local
      inflammatory findings in EA patients were recorded. RESULTS: EA had 60% greater
      AAV, 117% greater VAA, and 35% greater SAA than control subjects (p < 0.0001).
      Males composed a great proportion of the EA group (67%) than the control group
      (41%) (p = 0.0002). Inflamed appendage was found in sigmoid colon in 49% of
      cases, descending colon in 23%, and right colon in 19%. Peritoneal thickening was
      frequent (76%) and bowel wall thickening was common (47%). Diverticulosis
      coexisted incidentally in 28%. CONCLUSION: EA is associated with increased
      abdominal adipose tissue. EA can occur in both sexes at any age, but occurs at
      age 50 on average and more frequently in males. Patient with EA exhibited central
      hyperdense dot (79%), peritoneal thickening (76%), and bowel wall thickening
      (47%).

PMID- 29043405
TI  - [Focused update on dual antiplatelet treatment : ESC guidelines 2017].
AB  - Dual antiplatelet treatment (DAPT) is a cornerstone of maintenance medication of
      patients following elective percutaneous coronary interventions or an acute
      coronary syndrome (ACS), e. g. ST elevation myocardial infarction, non-ST
      elevation myocardial infarction and unstable angina. In recent years the
      inclusion of P2Y12 inhibition in addition to low-dose acetylsalicylic acid has
      been intensively debated. Following the introduction of the modern generation of
      drug-eluting stents for elective coronary interventions, the duration of the
      necessary DAPT has been clearly reduced. In patients with ACS the question arises
      when treatment with one of the more potent P2Y12 inhibitors, such as prasugrel
      and ticagrelor should be used instead of clopidogrel. A potential extension of
      DAPT beyond 12 months can be considered in high-risk patients after implantation
      of bioresorbable vascular scaffolds and following myocardial infarction. A
      special focus is on those patients who have already been treated with oral
      anticoagulants for stroke prevention in atrial fibrillation and require
      additional platelet inhibition following coronary stenting. This article
      summarizes and assesses the major recommendations given in the Focused Update
      DAPT 2017 of the European Society of Cardiology (ESC). In particular the
      recommendations address strategies to reduce an increased risk of bleeding based
      on clinical predictors.

PMID- 29043406
TI  - Predictive value of ScvO2 monitoring for pericardial tamponade after cardiac
      surgery.
AB  - BACKGROUND: We examined the predictive value of central venous oxygen saturation
      (ScvO2) changes regarding the occurrence of pericardial tamponade following
      cardiac surgery. METHODS: We retrospectively identified 66 consecutive patients
      in whom ScvO2 and arterial lactate levels were analyzed during an 8-h time
      interval preceding pericardiotomy due to pericardial tamponade (PT), and at
      equivalent time points in 30 control patients (C) who had an uncomplicated
      course. RESULTS: The median age of the patients was 74 years (interquartile
      range, 63-78). Three percent of procedures were re-operations. There were no
      differences between the baseline values of PT and C patients. Pericardiotomy was
      performed on average 1 day (0-3.5) after cardiac surgery. PT patients displayed a
      significant decline (p < 0.001) to lower ScvO2 levels (p < 0.001) and a
      significant increase (p = 0.005) to higher arterial lactate levels (p = 0.019)
      during the 8 h preceding pericardiotomy, whereas C patients did not (p = 0.440
      and p = 0.279, respectively). PT was associated with a longer hospital stay (p =
      0.04) and a higher in-hospital mortality (p = 0.008). An ScvO2 decline below 60%
      (p = 0.018), a delta ScvO2 decline greater than 5% (p = 0.001), and a delta
      lactate increase greater than 0.18 mmol/l (p = 0.002) during the 8 h preceding
      pericardiotomy were independently associated with PT. None of these parameters
      predicted in-hospital mortality. CONCLUSION: Deteriorations in ScvO2 might serve
      as an early marker of PT following cardiac surgery.

PMID- 29043407
TI  - Changes in Swallowing Symptoms and Esophageal Motility After Thyroid Surgery: A
      Prospective Cohort Study.
AB  - INTRODUCTION: Swallowing difficulties, the pathophysiology behind which is
      incompletely understood, have been reported in 47-83% of goiter patients referred
      for thyroidectomy. We aimed at examining the influence of thyroid surgery on
      swallowing symptoms and esophageal motility. METHODS: Thirty-three patients with
      benign nodular goiter undergoing thyroid surgery were included. All completed
      high-resolution esophageal manometry examinations and the goiter symptom scale
      score, assessed by the thyroid-specific patient-reported outcome measure. The
      evaluations were performed before and 6 months after surgery. RESULTS: Before
      surgery, the goiter symptom score was median 39 points (range 2-61), which
      improved to median five points (range 1-52) after surgery (p < 0.001). The
      motility parameters were within the limits of normal swallowing physiology, both
      before and after surgery. Only the upper esophageal sphincter (UES) pressure
      increased significantly from 70.6 +/- 27.7 to 87.7 +/- 43.2 mmHg after surgery (p
      = 0.04). Using regression analyses, there was no significant correlation between
      change in goiter symptoms and weight of the removed goiter, motility parameters,
      or motility disturbances. However, patients undergoing total thyroidectomy
      experienced a larger reduction in pressure in the area of the UES and former
      thyroid gland after surgery in comparison with patients undergoing less extensive
      surgery. CONCLUSIONS: Goiter symptoms improved significantly after thyroidectomy,
      but without correlation to esophageal motility disturbances. This information is
      essential when interpreting dysphagia in patients with nodular goiter, and when
      balancing patients' expectations to surgical goiter therapy. REGISTRATION NUMBER:
      NCT03100357 ( www.clinicaltrials.org ).

PMID- 29043408
TI  - What is the Cost of Free Cleft Surgery in the Middle East?
AB  - BACKGROUND: This project explores the costs of cleft lip and/or palate surgeries
      in Palestine and Sudan, two low- and middle-income countries (LMIC), in the
      Middle East. Our purpose is to examine the veracity of advertisements from
      international cleft organizations claiming that "250 US dollars (USD) covers the
      cost of a single cleft surgery." We hypothesize that the actual cost of surgery
      is greater than 250 USD. METHODS: Costs for each cleft surgery were organized
      broadly into 5 categories: hospital charges, personnel (time and money spent for
      health professionals to travel to LMIC, including lost wages), tests,
      consumables, and reusables. Each item was priced at market value during the time
      of data collection. Following itemization of actual costs, we compared the costs
      per cleft surgery among four surgical practice models: (1) visiting international
      surgical teams, (2) visiting international surgeon working with local teams, (3)
      local teams working at government hospitals, and (4) local teams working at
      private hospitals. RESULTS: Our results suggest that 250 USD is an underestimate
      of actual costs per cleft surgery in all models. The most expensive model in both
      Palestine and Sudan was the first model, visiting international teams performing
      all team functions; the cheapest surgical model in both countries was a local
      team working at government hospitals. The largest cost for any of these models is
      travel and lost wages for international team members. Eliminating this single
      cost (travel) decreases overall cost tremendously, but still does not approach
      the advertised cost of 250 USD. CONCLUSIONS: We conclude that 250 USD
      underestimates the actual costs to perform a single cleft surgery in Palestine
      and Sudan. If international cleft organizations are genuinely committed to
      creating sustainable international cleft programs, they should focus exclusively
      on training local professionals to perform surgery in hospitals of their own
      choosing.

PMID- 29043409
TI  - Margin Width of Resected Lepidic Lung Cancer Does Not Affect Recurrence After
      Sublobar Resection.
AB  - BACKGROUND: A sufficient resection margin is required for the sublobar resection
      of lung cancers. However, the width of the resection margin may not be important
      in lepidic adenocarcinoma, because such tumors are non- or minimally invasive.
      The purpose of this study was to determine the effect of resection margin width
      on the outcome of patients with lepidic-dominant adenocarcinoma after sublobar
      resection. METHODS: This study included 133 patients with small (<=2 cm),
      clinical N0M0 lung cancer who underwent sublobar resection with curative intent.
      The patients were divided into 4 groups: Group A, lepidic tumor with margin/tumor
      ratio <1; Group B, lepidic tumor with margin/tumor ratio >=1; Group C, non
      lepidic tumor with margin/tumor ratio <1; Group D, non-lepidic tumor with
      margin/tumor ratio >=1. The clinicopathological features and survival outcomes
      between Group A and B patients, and between Group C and D patients were compared.
      RESULTS: The 5-year recurrence-free survival (RFS) rates of Group A and B
      patients were both 100%. The 5-year RFS rates of Group C and D patients were 49.9
      and 97.1%, respectively (p = 0.009). By multivariate analysis, the margin/tumor
      ratio was a significant independent factor for recurrence in patients with non
      lepidic tumors (hazard ratio = 0.157, 95% confidence interval 0.027-0.898; p =
      0.037). CONCLUSIONS: Tumor recurrence after sublobar resection is not associated
      with short resection margins in patients with lepidic tumors. However, a short
      resection margin is a significant risk factor for recurrence in patients with non
      lepidic tumors.

PMID- 29043410
TI  - Determination of the absolute oral bioavailability of niraparib by simultaneous
      administration of a 14C-microtracer and therapeutic dose in cancer patients.
AB  - INTRODUCTION: Niraparib (ZejulaTM) is a poly(ADP-ribose) polymerase inhibitor
      recently approved by the US Food and Drug Administration for the maintenance
      treatment of patients with recurrent platinum-sensitive epithelial ovarian,
      fallopian tube, or primary peritoneal cancer who are in a complete or partial
      response to platinum-based chemotherapy. The pivotal phase III clinical trial has
      shown improved progression-free survival in patients receiving niraparib compared
      with those receiving placebo. PURPOSE: Since niraparib is administered orally, it
      is of interest to investigate the oral bioavailability (F po) of this novel
      compound, which is the aim of this study. METHODS: Six patients received an oral
      therapeutic dose of 300 mg niraparib, followed by a 15-min intravenous infusion
      of 100 ug 14C-niraparib with a radioactivity of approximately 100 nCi. The
      niraparib therapeutic dose was measured in plasma using a validated liquid
      chromatography-tandem mass spectrometry method, whereas the total 14C
      radioactivity and 14C-niraparib plasma levels were measured by accelerator mass
      spectrometry and a validated high performance liquid chromatography assay with
      AMS. RESULTS: The F po of niraparib was determined to be 72.7% in humans.

PMID- 29043411
TI  - Population pharmacokinetics of trastuzumab emtansine in previously treated
      patients with HER2-positive advanced gastric cancer (AGC).
AB  - PURPOSE: Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate
      comprising trastuzumab conjugated via a stable thioether linker to DM1, a highly
      potent cytotoxic agent. A population pharmacokinetics (PK) analysis was performed
      to characterize T-DM1 PK and evaluate the impact of patient characteristics on T
      DM1 PK in previously treated patients with HER2-positive advanced gastric cancer
      (AGC). METHODS: Following T-DM1 weekly or every three weeks dosing, T-DM1
      concentration measurements (n = 780) were collected from 136 patients in the
      GATSBY (NCT01641939) study and analyzed using nonlinear mixed effects modeling.
      The influence of demographic, baseline laboratory, and disease characteristics on
      T-DM1 PK was examined. RESULTS: T-DM1 PK was best described by a two-compartment
      model with parallel linear and nonlinear (Michaelis-Menten) elimination from the
      central compartment. The final population model estimated linear clearance (CL)
      of 0.79 L/day, volume of distribution in the central compartment (V c) of 4.48 L,
      distribution clearance (Q) of 0.62 L/day, volume of distribution in the
      peripheral compartment (V p) of 1.49 L, nonlinear CL of 2.06 L/day, and KM of
      1.63 MUg/mL. Parameter uncertainty was low to moderate for fixed effects, except
      KM (estimated with poor precision). Patients with high body weight and low
      baseline trastuzumab concentrations had significantly faster linear CL; those
      with higher body weight had significantly larger V c. CONCLUSIONS: In a HER2
      positive AGC population, T-DM1 PK was best described by a two-compartment model
      with parallel linear and nonlinear elimination. Baseline body weight and
      trastuzumab concentration were identified as significant covariates for T-DM1 PK
      in a HER2-positive AGC population.

PMID- 29043412
TI  - Randomized study of etirinotecan pegol versus irinotecan as second-line treatment
      for metastatic colorectal cancer.
AB  - PURPOSE: Etirinotecan pegol (EP) is a long-acting topoisomerase-I inhibitor
      designed to provide sustained exposure to SN-38 (active metabolite of
      irinotecan). This phase II study compared EP versus irinotecan as second-line
      treatment for KRAS-mutant, irinotecan-naive, metastatic colorectal cancer (mCRC).
      METHODS: Patients were randomized to EP 145 mg/m2 or irinotecan 350 mg/m2 Q21d
      until disease progression/unacceptable toxicity. The primary endpoint was
      progression-free survival (PFS) with response determined by central radiologic
      review (RECIST version 1.1). RESULTS: The study was terminated before completing
      accrual due to evolving standards of care. Eighty-three patients were randomized.
      Median PFS was longer with EP versus irinotecan (4.0 versus 2.8 months,
      respectively; HR 0.65; 95% CI 0.40-1.04; P = 0.07). Six-month PFS rates were 32.8
      and 15.4%, respectively. Median OS was 9.6 and 8.4 months in EP and irinotecan
      arms, respectively (HR 0.91; 95% CI 0.56-1.49). ORRs were 10 and 5%, respectively
      (P = 0.676); median DOR was significantly longer in EP arm (7.9 versus 1.4
      months; P = 0.018). The most common grade-3/4 adverse events for EP and
      irinotecan were diarrhea (21 vs 20%), neutropenia (10 vs 22%), abdominal pain (14
      vs 5%), nausea (14 vs 2%), and vomiting (12 vs 7%), respectively. CONCLUSION: EP
      is active and safe for second-line treatment of KRAS-mutant, irinotecan-naive
      mCRC.

PMID- 29043414
TI  - ?

PMID- 29043413
TI  - Cholecystokinin receptor antagonist alters pancreatic cancer microenvironment and
      increases efficacy of immune checkpoint antibody therapy in mice.
AB  - Advanced pancreatic ductal adenocarcinoma (PDAC) has typically been resistant to
      chemotherapy and immunotherapy; therefore, novel strategies are needed to enhance
      therapeutic response. Cholecystokinin (CCK) has been shown to stimulate growth of
      pancreatic cancer. CCK receptors (CCKRs) are present on pancreatic cancer cells,
      fibroblasts, and lymphocytes. We hypothesized that CCKR blockade would improve
      response to immune checkpoint antibodies by promoting influx of tumor
      infiltrating lymphocytes (TILs) and reducing fibrosis. We examined the effects of
      CCKR antagonists or immune checkpoint blockade antibodies alone or in combination
      in murine models of PDAC. Monotherapy with CCKR blockade significantly decreased
      tumor size and metastases in SCID mice with orthotopic PDAC, and in C57BL/6 mice,
      it reduced fibrosis and induced the influx of TILs. Immune-competent mice bearing
      syngeneic pancreatic cancer (Panc02 and mT3-2D) that were treated with the
      combination of CCK receptor antagonists and immune checkpoint blockade antibodies
      survived significantly longer with smaller tumors. Tumor immunohistochemical
      staining and flow cytometry demonstrated that the tumors of mice treated with the
      combination regimen had a significant reduction in Foxp3+ T-regulatory cells and
      an increase in CD4+ and CD8+ lymphocytes. Masson's trichrome stain analysis
      revealed 50% less fibrosis in the tumors of mice treated with CCKR antagonist
      compared to controls and compared to checkpoint antibody therapy. CCKR
      antagonists given with immune checkpoint antibody therapy represent a novel
      approach for improving survival of PDAC. The mechanism by which this combination
      therapy improves the survival of PDAC may be related to the decreased fibrosis
      and immune cells of the tumor microenvironment.

PMID- 29043415
TI  - ?

PMID- 29043416
TI  - ?

PMID- 29043417
TI  - Community-acquired pneumonia in children - a changing spectrum of disease.
AB  - Pneumonia remains the leading cause of death in children outside the neonatal
      period, despite advances in prevention and management. Over the last 20 years,
      there has been a substantial decrease in the incidence of childhood pneumonia and
      pneumonia-associated mortality. New conjugate vaccines against Haemophilus
      influenzae type b and Streptococcus pneumoniae have contributed to decreases in
      radiologic, clinical and complicated pneumonia cases and have reduced
      hospitalization and mortality. The importance of co-infections with multiple
      pathogens and the predominance of viral-associated disease are emerging. Better
      access to effective preventative and management strategies is needed in low- and
      middle-income countries, while new strategies are needed to address the residual
      burden of disease once these have been implemented.

PMID- 29043418
TI  - Lung magnetic resonance imaging for pneumonia in children.
AB  - Technical factors have historically limited the role of MRI in the evaluation of
      pneumonia in children in routine clinical practice. As imaging technology has
      advanced, recent studies utilizing practical MR imaging protocols have shown MRI
      to be an accurate potential alternative to CT for the evaluation of pneumonia and
      its complications. This article provides up-to-date MR imaging techniques that
      can be implemented in most radiology departments to evaluate pneumonia in
      children. Imaging findings in pneumonia on MRI are also reviewed. In addition,
      the current literature describing the diagnostic performance of MRI for pneumonia
      is discussed. Furthermore, potential risks and limitations of MRI for the
      evaluation of pneumonia in children are described.

PMID- 29043419
TI  - Computed tomography in children with community-acquired pneumonia.
AB  - Diagnostic imaging plays a significant role in both the diagnosis and treatment
      of complications of pneumonia in children and chest radiography is the imaging
      modality of choice. Computed tomography (CT) on the other hand, is not currently
      a first-line imaging tool for children with suspected uncomplicated community
      acquired pneumonia and is largely reserved for when complications of pneumonia
      are suspected or there is difficulty in differentiating pneumonia from other
      pathology. This review outlines the situations where CT needs to be considered in
      children with pneumonia, describes the imaging features of the parenchymal and
      pleural complications of pneumonia, discusses how CT may have a wider role in
      developing countries where human immunodeficiency virus (HIV) and tuberculosis
      are prevalent, makes note of the role of CT scanning for identifying missed
      foreign body aspiration and, lastly, addresses radiation concerns.

PMID- 29043420
TI  - Lung ultrasound for the diagnosis of community-acquired pneumonia in children.
AB  - Ultrasound (US) has been proposed as an alternative first-line imaging modality
      to diagnose community-acquired pneumonia in children. Lung US has the potential
      benefits over chest radiography of being radiation free, subject to fewer
      regulatory requirements, relatively lower cost and with immediate bedside
      availability of results. However, the uptake of lung US into clinical practice
      has been slow and it is not yet included in clinical guidelines for community
      acquired pneumonia in children. The aim of this review is to give an overview of
      the equipment and techniques used to perform lung US in children with suspected
      pneumonia and the interpretation of relevant sonographic findings. We also
      summarise the current evidence of diagnostic accuracy and reliability of lung US
      compared to alternative imaging modalities in children and critically consider
      the strengths and limitations of lung US for use in children presenting with
      suspected community-acquired pneumonia.

PMID- 29043421
TI  - The duplicated collecting system of the urinary tract: embryology, imaging
      appearances and clinical considerations.
AB  - Duplication anomalies of the urinary collecting system are common and can be
      discovered and characterized with multiple imaging modalities. The embryology,
      imaging manifestations and clinical ramifications of duplicated ureters and renal
      collecting systems vary from a normal anatomical variant to urological pathology
      and are discussed and illustrated in this review.

PMID- 29043422
TI  - Guidelines for the use of chest radiographs in community-acquired pneumonia in
      children and adolescents.
AB  - National guidance from the United Kingdom and the United States on community
      acquired pneumonia in children states that chest radiographs are not recommended
      routinely in uncomplicated cases. The main reason in the ambulatory setting is
      that there is no evidence of a substantial impact on clinical outcomes. However
      clinical practice and adherence to guidance is multifactorial and includes the
      clinical context (developed vs. developing world), the confidence of the
      attending physician, the changing incidence of complications (according to the
      success of immunisation programs), the availability of alternative imaging (and
      its relationship to perceived risks of radiation) and the reliability of the
      interpretation of imaging. In practice, chest radiographs are performed
      frequently for suspected pneumonia in children. Time pressures facing clinicians
      at the front line, difficulties in distinguishing which children require
      admission, restricted bed numbers for admissions, imaging-resource limitations,
      perceptions regarding risk from procedures, novel imaging modalities and the
      probability of other causes for the child's presentation all need to be factored
      into a guideline. Other drivers that often weigh in, depending on the setting,
      include cost-effectiveness and the fear of litigation. Not all guidelines
      designed for the developed world can therefore be applied to the developing
      world, and practice guidelines require regular review in the context of new
      information. In addition, radiologists must improve radiographic diagnosis of
      pneumonia, reach consensus on the interpretive terminology that clarifies their
      confidence regarding the presence of pneumonia and act to replace one imaging
      technique with another whenever there is proof of improved accuracy or
      reliability.

PMID- 29043424
TI  - Imaging community-acquired pneumonia in children.

PMID- 29043423
TI  - Preliminary report from the World Health Organisation Chest Radiography in
      Epidemiological Studies project.
AB  - Childhood pneumonia is among the leading infectious causes of mortality in
      children younger than 5 years of age globally. Streptococcus pneumoniae
      (pneumococcus) is the leading infectious cause of childhood bacterial pneumonia.
      The diagnosis of childhood pneumonia remains a critical epidemiological task for
      monitoring vaccine and treatment program effectiveness. The chest radiograph
      remains the most readily available and common imaging modality to assess
      childhood pneumonia. In 1997, the World Health Organization Radiology Working
      Group was established to provide a consensus method for the standardized
      definition for the interpretation of pediatric frontal chest radiographs, for use
      in bacterial vaccine efficacy trials in children. The definition was not designed
      for use in individual patient clinical management because of its emphasis on
      specificity at the expense of sensitivity. These definitions and endpoint
      conclusions were published in 2001 and an analysis of observer variation for
      these conclusions using a reference library of chest radiographs was published in
      2005. In response to the technical needs identified through subsequent meetings,
      the World Health Organization Chest Radiography in Epidemiological Studies (CRES)
      project was initiated and is designed to be a continuation of the World Health
      Organization Radiology Working Group. The aims of the World Health Organization
      CRES project are to clarify the definitions used in the World Health Organization
      defined standardized interpretation of pediatric chest radiographs in bacterial
      vaccine impact and pneumonia epidemiological studies, reinforce the focus on
      reproducible chest radiograph readings, provide training and support with World
      Health Organization defined standardized interpretation of chest radiographs and
      develop guidelines and tools for investigators and site staff to assist in
      obtaining high-quality chest radiographs.

PMID- 29043425
TI  - Arylamine N-acetyltransferase 1 in situ N-acetylation on CD3+ peripheral blood
      mononuclear cells correlate with NATb mRNA and NAT1 haplotype.
AB  - Human arylamine N-acetyltransferase 1 (NAT1) is responsible for the activation
      and elimination of xenobiotic compounds and carcinogens. Genetic polymorphisms in
      NAT1 modify both drug efficacy and toxicity. Previous studies have suggested a
      role for NAT1 in the development of several diseases. The aim of the present
      study was to evaluate NAT1 protein expression and in situ N-acetylation capacity
      in peripheral blood mononuclear cells (PBMC), as well as their possible
      associations with the expression of NAT1 transcript and NAT1 genotype. We report
      NAT1 protein, mRNA levels, and N-acetylation in situ activity for PBMC obtained
      from healthy donors. NAT1-specific protein expression was higher in CD3+ cells
      than other major immune cell subtypes (CD19 or CD56 cells). N-acetylation of pABA
      varied markedly among the PBMC of participants, but correlated very significantly
      with levels of NAT1 transcripts. NAT1*4 subjects showed significantly (p = 0.017)
      higher apparent pABA V max of 71.3 +/- 3.7 versus the NAT1*14B subjects apparent
      V max of 58.5 +/- 2.5 nmoles Ac-pABA/24 h/million cells. Levels of pABA N
      acetylation activity at each concentration of substrate evaluated also
      significantly correlated with NAT1 mRNA levels for all samples (p < 0.0001). This
      highly significant correlation was maintained for samples with the NAT1*4 (p =
      0.002) and NAT1*14B haplotypes (p = 0.0106). These results provide the first
      documentation that NAT1-catalyzed N-acetylation in PBMC is higher in T cell than
      in other immune cell subtypes and that individual variation in N-acetylation
      capacity is dependent upon NAT1 mRNA and NAT1 haplotype.

PMID- 29043426
TI  - Roles of cytosolic phospholipase A2alpha in reproductive and systemic toxicities
      in 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed mice.
AB  - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces a variety of
      toxicities upon binding of TCDD to aryl hydrocarbon receptor. Although this
      binding upregulates the synthesis of prostaglandins and their related lipid
      mediators via cytosolic phospholipase A2alpha (cPLA2alpha), toxicological
      significance of this signaling pathway remains elusive. Herein, we investigated
      the roles of cPLA2alpha in TCDD toxicities using cPLA2alpha-null mice. In a first
      set of experiments, pregnant mice were orally administered TCDD at a dose of 40
      MUg/kg on gestation day (GD) 12.5, and fetuses were collected on GD 18 for
      subsequent analyses. The number of live male fetuses of cPLA2alpha-null type was
      significantly less than that of wild-type in TCDD-exposed litters. TCDD-induced
      hydronephrosis was more severe in wild-type fetuses than in cPLA2alpha-null
      fetuses regardless of sex, and kidney expression levels of the inflammatory
      cytokines interleukin-1beta and tumor necrosis factor-alpha were increased in a
      cPLA2alpha-dependent manner in TCDD-exposed fetuses. In a second set of
      experiments, following intraperitoneal administration of TCDD at 50 MUg/kg, body
      weight of the male adult mice was decreased within 2 days in wild-type mice but
      was not changed in cPLA2alpha-null mice. In addition, TCDD-induced lipid
      accumulation in the livers of cPLA2alpha-null mice was at an intermediate level
      compared with TCDD-exposed wild-type and vehicle-control mice. In conclusion, the
      present results show that cPLA2alpha is involved in TCDD-induced body weight
      loss, lipid accumulation in the liver, fetal hydronephrosis, and cytokine gene
      expression, and that the molecular basis of TCDD toxicity differs considerably
      between target tissues and life stages.

PMID- 29043427
TI  - Ambient air pollution and emergency department visits for asthma in Erie County,
      New York 2007-2012.
AB  - PURPOSE: 8% of the US population has asthma. Air pollution is linked to
      exacerbation in susceptible individuals. The objective was to identify air
      pollutants that increased the risk of asthma emergency department visits during a
      time wherein a polluting factory was criminally convicted, changing local air
      pollutant levels. METHODS: An ecological time-series design used a daily count of
      asthma emergency visits from 2007 to 2012 as the dependent variable. Independent
      variables air pollutants (NO2, PM2.5 CO, and O3), controlling for meteorological
      conditions, were analyzed using time-series and Poisson GLM models. RESULTS:
      76,651 emergency asthma visits were included with an average of 35 visits per day
      (SD = 9.2, range 11-80) in a stationary time series. Increased visit volume in
      fall and spring had no associations to the air pollutants. Associations between
      individual air pollutants occurred in otherwise low-volume months for asthma
      emergency visits. The strongest relationship was an 11.6% increase in the asthma
      emergency visit rate during the month of June. In monthly groupings that removed
      most of the autumn and spring months, O3, PM2.5, CO, and NO2 were associated with
      5, 4, 2, and 2% increases in asthma emergency visits, respectively. CO was the
      only pollutant with a negative association with asthma emergency visits,
      occurring in the month of April. CONCLUSIONS: Pollutants NO2, PM2.5 CO, and O3
      were associated with increased emergency asthma visits in some, but not all
      months of the year. Air pollution's impact on asthma emergencies may be masked by
      other, more influential seasonal triggers, such as infections or allergies.

PMID- 29043429
TI  - Reply to the Letter to the Editor by Reza Pakzad and Saeid Safiri, integration of
      MRI to clinical nomogram for predicting pathological stage before radical
      prostatectomy: bias in the prediction model.

PMID- 29043428
TI  - Magnetic resonance imaging for clinical management of rectal cancer: Updated
      recommendations from the 2016 European Society of Gastrointestinal and Abdominal
      Radiology (ESGAR) consensus meeting.
AB  - OBJECTIVES: To update the 2012 ESGAR consensus guidelines on the acquisition,
      interpretation and reporting of magnetic resonance imaging (MRI) for clinical
      staging and restaging of rectal cancer. METHODS: Fourteen abdominal imaging
      experts from the European Society of Gastrointestinal and Abdominal Radiology
      (ESGAR) participated in a consensus meeting, organised according to an adaptation
      of the RAND-UCLA Appropriateness Method. Two independent (non-voting) Chairs
      facilitated the meeting. 246 items were scored (comprising 229 items from the
      previous 2012 consensus and 17 additional items) and classified as 'appropriate'
      or 'inappropriate' (defined by >= 80 % consensus) or uncertain (defined by < 80 %
      consensus). RESULTS: Consensus was reached for 226 (92 %) of items. From these
      recommendations regarding hardware, patient preparation, imaging sequences and
      acquisition, criteria for MR imaging evaluation and reporting structure were
      constructed. The main additions to the 2012 consensus include recommendations
      regarding use of diffusion-weighted imaging, criteria for nodal staging and a
      recommended structured report template. CONCLUSIONS: These updated expert
      consensus recommendations should be used as clinical guidelines for primary
      staging and restaging of rectal cancer using MRI. KEY POINTS: * These guidelines
      present recommendations for staging and reporting of rectal cancer. * The
      guidelines were constructed through consensus amongst 14 pelvic imaging experts.
      * Consensus was reached by the experts for 92 % of the 246 items discussed. *
      Practical guidelines for nodal staging are proposed. * A structured reporting
      template is presented.

PMID- 29043430
TI  - Response to: Greenlight(r) users should move from photoselective vaporization to
      endoscopic enucleation in larger prostates : Benoit Peyronnet, Vincent Misrai,
      Tev Aho, Henry Woo, Thomas Herrmann, Fernando Gomez-Sancha.

PMID- 29043431
TI  - 99mTc-HDP bone scintigraphy and 18F-sodiumfluoride PET/CT in primary staging of
      patients with prostate cancer.
AB  - INTRODUCTION/AIM: Correct staging of patients with prostate cancer is important
      for treatment planning and prognosis. Although bone scintigraphy with 99mTc
      phosphonates (BS) is generally advised for staging by guidelines in high risk
      prostate cancer, this imaging technique is hampered by a high rate of
      inconclusive results and moderate accuracy. Potentially better imaging techniques
      for detection of bone metastases such as 18F-sodiumfluoride PET/CT (NaF PET/CT)
      are therefore being evaluated. In this observational cohort study we evaluate the
      performance and clinical impact of both BS and NaF PET/CT in primary staging of
      patients with prostate cancer. METHODS: The first of two cohorts consisted of
      patients who received a BS while the second included patients who received a NaF
      PET/CT for primary staging of prostate cancer. For both cohorts the number of
      positive, negative and equivocal findings, calculated diagnostic performance of
      the imaging modality in terms of sensitivity and specificity, as well as the
      impact on clinical management were studied. The ranges of the diagnostic
      performance were calculated both assuming that equivocal findings were positive
      and assuming that they were negative for bone metastases. For the NaF PET/CT
      cohort the number of patients with signs of lymph node metastases on low dose CT
      were also recorded, including the impact of these findings on clinical
      management. RESULTS: One-hundred-and-four patients underwent NaF PET/CT, whereas
      122 patients underwent BS. Sensitivities of 97-100 and 84-95% and specificities
      of 98-100 and 72-100% were found on a patient basis for detection of bone
      metastases with NaF PET/CT and BS, respectively. Equivocal findings warranted
      further diagnostic procedures in 2% of the patients in the NaF cohort and in 16%
      in the BS cohort. In addition NaF PET/CT demonstrated lymph node metastases in
      50% of the included patients, of which 25% showed evidence of lymph node
      metastases only. CONCLUSION: Our data indicate better diagnostic performance of
      NaF PET/CT compared to BS for detection of bone metastases in primary staging of
      prostate cancer patients. Less equivocal findings are encountered with NaF
      PET/CT. Moreover, NaF PET/CT has additional value over BS since lymph node
      metastases are encountered frequently.

PMID- 29043433
TI  - MCPIP1 inhibits coxsackievirus B3 replication by targeting viral RNA and
      negatively regulates virus-induced inflammation.
AB  - Monocyte chemotactic protein-induced protein 1(MCPIP1) is identified as an
      important inflammatory regulator during immune response. MCPIP1 possesses
      antiviral activities against several viruses, such as Japanese encephalitis.
      However, its role on Coxsackievirus B3 (CVB3) infection, a positive-stranded RNA
      virus, has not been addressed. Here, we reported that MCPIP1 was up-regulated in
      cardiomyocytes by CVB3 infection and in hearts and pancreas of infected mice.
      Then we found that overexpression of MCPIP1 inhibited CVB3 replication and
      knockdown of it promoted virus replication. Luciferase assay demonstrated MCPIP1
      targeting non-ARE region of CVB3 3'UTR, which was dependent on its RNase, RNA
      binding and oligomerization abilities, but not deubiquitinase activity. We
      further verified that MCPIP1 negatively regulated CVB3-induced inflammatory
      response in macrophages. Thus, our data suggest MCPIP1 as a potent host defense
      against CVB3 infection and viral myocarditis.

PMID- 29043432
TI  - Recent advances in pharmacological, hormonal, and nutritional intervention for
      sarcopenia.
AB  - Sarcopenia, the age-related loss of skeletal muscle mass, is characterized by a
      deterioration of muscle quantity and quality leading to a gradual slowing of
      movement, a decline in strength and power, increased risk of fall-related injury,
      and often frailty. This review focuses on the recent advances of pharmacological,
      hormonal, and nutritional approaches for attenuating sarcopenia. The article is
      composed of the data reported in many basic and some clinical studies for
      mammalian muscles. Resistance training combined with amino acid-containing
      supplements is the gold standard to prevent sarcopenia. Supplementation with
      proteins (amino acids) only did not influence sarcopenic symptoms. A myostatin
      inhibiting strategy is the most important candidate to prevent sarcopenia in
      humans. Milder caloric restriction (CR, 15-25%) would also be effective for age
      related muscle atrophy in humans. Supplementation with ursolic acid and ghrelin
      is an intriguing candidate to combat sarcopenia, although further systematic and
      fundamental research is needed on this treatment.

PMID- 29043434
TI  - [Spondyloarthritides].
AB  - Spondyloarthritides (SpA) are inflammatory rheumatic diseases affecting the axial
      skeleton, peripheral joints and entheses, and also manifest at extraskeletal
      sites. According to the more recently introduced nomenclature, predominant axial
      SpA is distinguished from predominant peripheral SpA. Axial SpA is further
      divided into radiographic and nonradiographic axial SpA. Genetic factors are
      relevant, with HLA-B27 being most important. The interleukin 23/17 pathway seems
      to be relevant and points towards new therapeutic targets. Inflammatory back pain
      is the leading symptom in axial SpA and has certain characteristics. In addition,
      HLA-B27 and sacroiliitis on imaging are important for diagnosis. Therapy consists
      of physiotherapy, nonsteroidal anti-inflammatory drugs (first line) and
      biologicals (second line). Conventional disease-modifying antirheumatic drugs are
      effective only in peripheral arthritis.

PMID- 29043435
TI  - How conceptual overlap and modality pairings affect task-switching and mixing
      costs.
AB  - Manipulating the pairings of stimulus and response modalities has been shown to
      affect how response selection processes for distinct tasks interact. For example,
      Stephan and Koch (Psychol Res 75(6):491-498, 2011) found smaller performance
      costs when participants switched between visual-manual (VM) and auditory-vocal
      (AV) tasks (modality compatible; MC) compared to between visual-vocal (VV) and
      auditory-manual (AM) tasks (modality incompatible; MI). However, in the Stephan
      and Koch study, there was conceptual overlap between one set of stimuli and one
      set of responses. For the MC pair, these stimuli and responses belonged to the
      same task, whereas for the MI pair, they belonged to different tasks. To examine
      how conceptual overlap affected switch and mixing costs, we conducted two
      experiments. Experiment 1a was a near replication of Stephan and Koch in which
      conceptual overlap was present in the MC AV task. In contrast, Experiment 1b
      reduced conceptual overlap within the MC AV task and increased it in the MI VV
      task. In Experiment 1a, we replicated Stephan and Koch's findings: larger switch
      costs were observed for the MI pair; in Experiment 1b, we found numerically
      greater switch costs in the MC condition. In Experiment 2, we reduced conceptual
      overlap in both tasks and found no effect of modality compatibility on switch
      costs. However, mixing costs were primarily driven by modality compatibility,
      regardless of conceptual overlap. These results highlight the different roles
      that conceptual overlap and modality pairings have on switch and mixing costs.

PMID- 29043436
TI  - Cervical dilation balloon combined with intravenous drip of oxytocin for
      induction of term labor: a multicenter clinical trial.
AB  - OBJECTIVE: This study aimed to investigate the effectiveness and safety of a
      method combining double-balloon catheter for cervical ripening and intravenous
      drip of oxytocin on the induction of term labor, providing the reference for
      clinical safety. METHODS: A total of 120 pregnant women with a gestation between
      37+0 and  41+6 weeks, indications of labor induction, singleton pregnancy with
      cephalic presentation were enrolled. The patients were divided into the research
      group receiving cervical dilation balloon combined with intravenous drip of
      oxytocin and the control group receiving an intravenous drip of oxytocin at a
      concentration of 0.5% for labor induction (n = 60 for each). The effectiveness
      and safety of labor induction were evaluated by the rates of successful cervical
      ripening promotion and labor induction, as well as the vaginal delivery rate,
      induced labor time, total duration of labor, the total amount of postpartum
      hemorrhage within 24 h after giving birth, the incidences of postpartum
      hemorrhage, cervical laceration, puerperal infection and neonatal outcomes.
      RESULTS: There was no statistical difference in the basal demographic and
      clinical characteristics, including ages, gestational weeks, delivery times and
      Bishop scores at admission between two groups. The rate of successful cervical
      ripening promotion (research vs. control = 90.00% vs. 55.00%), the rate of
      successful induction (95.00% vs. 40.00%), the vaginal delivery rate (93.33% vs.
      63.33%), the induced labor time (15.03 +/- 5.40 vs. 30.68 +/- 10.82 h), and the
      total duration of labor (8.12 +/- 2.65 vs. 15.01 +/- 6.06 h) were significantly
      different between two groups (all P < 0.05). There was no significant difference
      in the total amount of postpartum hemorrhage, incidences of postpartum
      hemorrhage, cervical laceration, puerperal infection as well as the neonatal
      outcomes, including neonatal weight, neonatal asphyxia and incidence of meconium
      aspiration syndrome between two groups. CONCLUSIONS: Compared to labor induction
      of oxytocin, the method combining double-balloon catheter for cervical ripening
      and intravenous drip of oxytocin for the induction of term labor has a higher
      vaginal delivery rate, shorter total duration of labor, and does not increase the
      incidences of postpartum hemorrhage and neonatal infection, which is a more
      effective and safer method for induction of term labor.

PMID- 29043439
TI  - [Bilateral corectopia with lenses displaced in opposite directions].

PMID- 29043437
TI  - Differences in the prognosis of HPV16-positive patients with squamous cell
      carcinoma of head and neck according to viral load and expression of P16.
AB  - PURPOSE: To evaluate the impact of HPV16 load (VL-the number of virus genome
      copies per cell) and P16 expression on prognosis of patients with squamous cell
      carcinomas (SCCs) of head and neck (HN). MATERIALS AND METHODS: HPV16 presence
      was assessed in the group of 109 patients with HNSCCs by quantitative polymerase
      chain reaction (qPCR). VL (assessed by qPCR) and P16 expression (evaluated by
      immunohistochemistry) were analysed only in the subgroup of HPV16-positive
      tumours. These features were correlated with 5-year overall survival (OS) and
      disease-free survival (DFS). RESULTS: HPV16 infection was found in 36 tumours
      (33.0%). Virus-positive patients had better OS and DFS than those without
      infection (P = 0.041 and 0.005). Among HPV16-positive HNSCCs, 18 (50.0%) had
      higher VL (median value > 6764.3 copies/cell) and 25 (73.5%) P16 over expression.
      The significant differences in OS and DFS (P = 0.008 and 0.004) were noticed
      according to VL, wherein 100% DFS was found for patients with higher VL.
      According to P16 expression, significant difference was found only for OS (P =
      0.020). In multivariate analysis, VL (P = 0.045; HR = 2.795; CI 0.121-1.060) and
      the level of smoking (P = 0.023, HR = 2.253; CI 1.124-4.514) were independent
      factors affecting DFS of HPV16-positive patients. CONCLUSION: On the basis of
      viral load, it is possible to differentiate prognosis of patients with HPV16
      positive HNSCCs. In this subgroup, viral load has stronger prognostic potential
      than P16 expression.

PMID- 29043438
TI  - Safety and efficacy of multiple cyclocoagulation of ciliary bodies by high
      intensity focused ultrasound in patients with glaucoma.
AB  - PURPOSE: To evaluate long-term efficacy and safety of repeated ultrasonic
      circular cyclocoagulation (UCCC) in patients with uncontrolled glaucoma. METHODS:
      Forty eyes of 40 patients affected by primary or secondary uncontrolled glaucoma
      under maximal tolerated medical therapy were enrolled in this prospective non
      comparative case series study. A complete ophthalmic examination was performed
      before and after each month for 1 year. The UCCC treatment was repeated at 4
      months if the intraocular pressure (IOP) was > 21 mmHg without major
      complications. Complete success was defined as a final IOP > 5 mmHg and <= 21
      mmHg without hypotensive medication adjunction and no major or vision-threatening
      complications. RESULTS: The mean preoperative IOP was 32.5 +/- 9.9 mmHg. Four
      months after the first UCCC treatment the overall IOP reduction was 27.8%. Twenty
      two of the treated eyes did not achieve the complete success and a second
      treatment was performed in 20 of these eyes. Four months after the second UCCC
      procedure, the IOP reduction was 20.3% from preoperative values and 34.7% from
      baseline. Twelve of the retreated eyes needed a third treatment. Four months
      after the third UCCC treatment, the overall IOP reduction was 34% and 52.6% from
      baseline. No major complications occurred during or after any of the procedures.
      At 12 months, complete success was achieved in 85% (34/40) of treated eyes, with
      a maximum of three procedures and a significant medication reduction.
      CONCLUSIONS: Multiple UCCC treatments are safe, and additional treatments
      increase the overall procedure efficacy.

PMID- 29043440
TI  - [Boston keratoprosthesis: 73 eyes from Germany : An overview of experiences from
      two centers].
AB  - BACKGROUND: The Boston Keratoprosthesis (B-KPro) is a therapeutic option for
      corneal replacement for visual rehabilitation in eyes with poor a prognosis for
      penetrating keratoplasty (high-risk eyes). Since 2009, this approach has been
      used in the MVZ Prof. Neuhann, Munich, and since 2013 also at the Department of
      Ophthalmology, University of Cologne. An overview of results from the first 73
      eyes in these departments is presented. METHODS: All recipient eyes of both
      centers which received a B-KPro type I (BI-KPro) between November 2009 and March
      2017 were included. Indications, preoperative findings, intraoperative
      procedures, and clinical results, as well as postoperative complication and
      retention rates were documented and analyzed. RESULTS: A total of 73 eyes from 68
      patients (mean age 55 +/- 21.1 years, range 7 months-93 years; 26 women, 42 men)
      were treated with a BI-KPro. In 53 eyes (72.6%) the BI-KPro was implanted due to
      corneal graft failure, whereas BI-KPro was used as the primary corneal
      replacement in 20 eyes (27.4%). In 46 eyes (63.0%) a long-term increase in visual
      acuity was achieved and in 21.9% visual acuity was stabilized, while a decrease
      in preoperative visual acuity occurred in 15.1% of cases. During an average
      follow-up of 24.7 +/- 23.0 months (range 1-78 months), 1.7 +/- 2.4 re
      interventions (range 0-9) were required. Only 4 keratoprostheses (5.5%) could not
      be retained. In 3 eyes (4.2%), a change of the BI-KPro device was necessary.
      CONCLUSION: There is a wide range of indications for BI-KPro in eyes with a poor
      prognosis for conventional keratoplasty. The surgical technique is safe but with
      a notable postoperative complication rate, which does not seem to decrease in the
      medium or long term. The retention rate is excellent for eyes without stem cell
      deficiency. Nevertheless, the BI-KPro is the only therapeutic option for high
      risk eyes and leads to a gain in visual acuity in most cases.

PMID- 29043441
TI  - Patients' view of routine follow-up after breast cancer treatment.
AB  - BACKGROUND: To assess emotional distress, anxiety and stress reactions in breast
      cancer (BC) patients before the follow-up visits. STUDY DESIGN: Between September
      2009 and December 2011 a total of 284 patients completed the BC-psychosocial
      assessment screening scale (PASS) and a questionnaire about their views of follow
      up after treatment for BC. RESULTS: Of the patients 64% reported low level of
      distress on the BC-PASS. The mean scores on the physical well-being scale was
      5.3, the satisfaction/sense of coherence scale 7.4, and the emotional distress
      scale 8.1. Women rated mammography as the most important component (71%),
      followed by breast ultrasound (63%) and the consultation with the physician
      (60%). Of the patients 94% were satisfied with the current follow-up regimen.
      CONCLUSIONS: In this series BC patients were satisfied with their aftercare.
      Mammography was thought to be the most important component of aftercare. Patient
      reported outcomes should be taken into account when planning follow-up.

PMID- 29043442
TI  - Sex and gender matters : A sex-specific analysis of original articles published
      in the Wiener klinische Wochenschrift between 2013 and 2015.
AB  - BACKGROUND: The variables sex and gender are significantly related to health and
      disease of women and men. Aiming at quality research, biomedical publications
      need to account for the key variables sex and gender. METHODS: All original
      articles published in the Wiener klinische Wochenschrift between 2013 and 2015
      were extracted into a database. As a result, the 195 published articles were
      selected for review led by the Sex and Gender Equity in Research Guidelines
      (SAGER) by the European Association of Science Editors (EASE). The slightest
      indications of mentioning sex and/or gender were assessed by two reviewers
      independently from one another. RESULTS: Of the 195 publications 4 specified sex
      and/or gender in the title, and 62 in the abstract. None of the authors reported
      whether the variables sex and/or gender may have relevance and were taken into
      account in the design of the study. Of the 195 publications 48 mentioned the
      potential implications of sex and/or gender on the study results. CONCLUSION: In
      the time span studied most of the selected articles of this journal did not
      account for the variables sex and/or gender systematically or adequately. For
      future research the existing guidelines can help authors and editors to overcome
      gender bias due to inadequate methods. Applying sex and gender-sensitive methods
      to biomedical and health research is necessary for high quality and as a
      precondition for results which are generalizable and applicable to both women and
      men.

PMID- 29043443
TI  - Reply.

PMID- 29043444
TI  - Combined treatment with alendronate and Drynaria rhizome extracts : Effect on
      fracture healing in osteoporotic rats.
AB  - The effects of both alendronate (ALN) and Drynaria rhizome extracts (DRE) alone
      could promote bone healing in osteoporotic fractures but there are no reports
      about the combined use of ALN and DRE for promotion of bone healing of fractures
      in osteoporotic settings. This study investigated the effects of ALN plus DRE on
      fractures in osteopenic rats. Osteopenic rats underwent unilateral transverse
      osteotomy on the femur fixed by a sterilized Kirschner wire 2 weeks after
      intragastric administration of retinoic acid (80 mg/kg body weight/day).
      Subsequently, the animals were randomly divided into four groups: control, ALN,
      DRE and ALN + DRE. All rats from groups ALN, DRE and ALN + DRE received ALN (40
      mg/kg, weekly), DRE (90 mg/kg/day), or both for 2, 4 and 6 weeks. The results of
      our study indicated that all treatment promoted fracture healing and callus
      formation compared to controls but ALN + DRE treatment showed significantly
      stronger effects than ALN or DRE alone in histological, X-ray and biomechanical
      tests. These results seem to indicate that combined treatment with ALN and DRE
      has an additive effect on fracture healing and callus formation in osteoporotic
      rats.

PMID- 29043446
TI  - ?

PMID- 29043445
TI  - The role of intermediate filaments in maintaining integrity and function of
      intestinal epithelial cells after massive bowel resection in a rat.
AB  - PURPOSE: Intermediate filaments (IFs) are a part of the cytoskeleton that extend
      throughout the cytoplasm of all cells and function in the maintenance of cell
      shape by bearing tension and serving as structural components of the nuclear
      lamina. In normal intestine, IFs provide a tissue-specific three-dimensional
      scaffolding with unique context-dependent organizational features. The purpose of
      this study was to evaluate the role of IFs during intestinal adaptation in a rat
      model of short bowel syndrome (SBS). MATERIALS AND METHODS: Male rats were
      divided into two groups: Sham rats underwent bowel transection and SBS rats
      underwent a 75% bowel resection. Parameters of intestinal adaptation, enterocyte
      proliferation and apoptosis were determined 2 weeks after operation. Illumina's
      Digital Gene Expression (DGE) analysis was used to determine the cytoskeleton
      related gene expression profiling. IF-related genes and protein expression were
      determined using real-time PCR, Western blotting and immunohistochemistry.
      RESULTS: Massive small bowel resection resulted in a significant increase in
      enterocyte proliferation and concomitant increase in cell apoptosis. From the
      total number of 20,000 probes, 16 cytoskeleton-related genes were investigated.
      Between these genes, only myosin and tubulin levels were upregulated in SBS
      compared to sham animals. Between IF-related genes, desmin, vimentin and lamin
      levels were down-regulated and keratin and neurofilament remain unchanged. The
      levels of TGF-beta, vimentin and desmin gene and protein were down-regulated in
      resected rats (vs sham animals). CONCLUSIONS: Two weeks following massive bowel
      resection in rats, the accelerated cell turnover was accompanied by a stimulated
      microfilaments and microtubules, and by inhibited intermediate filaments.
      Resistance to cell compression rather that maintenance of cell-shape by bearing
      tension are responsible for contraction, motility and postmitotic cell separation
      in a late stage of intestinal adaptation.

PMID- 29043447
TI  - [Lean management in the pathology laboratory].

PMID- 29043448
TI  - [Retinoblastoma and retinocytoma (retinoma)].
AB  - Retinoblastomas are extremely rare withabout half of the cases being hereditary
      eye neoplasms in young children. They show highly proliferative, CRX-positive
      undifferentiated tumour cells (occasionally forming rosettes). Staging is
      performed according to the pTNM classification and the International
      Retinoblastoma Staging System (IRSS). The diagnostic basis for systemic
      administration of chemotherapy and/or radiation is postlaminar optic nerve
      invasion, massive choroidal tumour infiltration, scleral invasion or even
      extraocular invasion. In cases that are difficult to diagnose,
      immunohistochemical stains (CRX and Ki67) may be very helpful. Retinocytomas
      (retinomas) completely lack undifferentiated tumour cell areas, show an exclusive
      photoreceptor differentiation and an exceptionally low Ki67 index.

PMID- 29043449
TI  - Influence of culture conditions towards optimal carotenoid production by Gordonia
      alkanivorans strain 1B.
AB  - With the increasing awareness on the toxicity of several synthetic dyes, demand
      for pigments from natural sources, such as microbial carotenoids, has gained
      interest as a promising safe alternative colour additive. In this study, a
      surface response methodology based on the Doehlert distribution for two factors
      [% of glucose in a mixture of glucose + fructose (10 g/L total sugars), and
      sulfate concentration] was used towards the optimal carotenoids production by
      Gordonia alkanivorans strain 1B in the presence of light (400 lx). Time influence
      on pigment production by this bacterium was also evaluated, as well as the cell
      viability profile during longer incubation periods at optimal conditions. Indeed,
      the highest carotenoid production (2596-3100 MUg/gDCW) was obtained when strain
      1B was cultivated in the optimal conditions: glucose 10 g/L and sulfate >= 22
      mg/L, in the presence of light for 19 days at 30  degrees C, 150 rpm. Flow
      cytometry showed that the highest production was somehow related with the
      cellular stress. These results highlight the great potential of strain 1B as a
      new hyperpigment producer to be exploited towards several applications.

PMID- 29043450
TI  - Immobilization of lipase on carboxylic acid-modified silica nanoparticles for
      olive oil glycerolysis.
AB  - In this study, the silica nanoparticles surface was modified by carboxylic acid
      with different number of alkyl chain and two different lipases were immobilized
      on it to increase the glycerolysis activity of the immobilized lipases in organic
      solvent system. Silica nanoparticles of about 15 nm diameter were grafted with
      various carboxylic acid modifiers from valeric, caprylic, capric, lauric, stearic
      and oleic acids. Lipases from Candida antarctica and Candida rugosa were
      immobilized onto the carboxylic acid, modified silica nanoparticles and used in
      the mono and diglycerides production through glycerolysis with or without organic
      solvents. When lipases immobilized on stearic acid-modified silica nanoparticles,
      both lipases gave higher activity compared to their corresponding free lipases.
      Immobilized C. rugosa were stable and reused for 11 cycles without loss in
      activity. The kinetic parameters, K m and V max of free and immobilized lipases
      were found using Lineweaver-Burk model. Results indicated that the immobilized
      lipase had a lower K m and V max when compared with the free lipase.

PMID- 29043451
TI  - Weather and eared grebe winter migration near the Great Salt Lake, Utah.
AB  - This study provides insight from the use of weather radar observations to
      understand the characteristics of the eared grebe migration near the Great Salt
      Lake (GSL) and provides unique information on weather conditions connected to
      these migration events. Doppler weather radar measurements from the Salt Lake
      City, Utah WSR-88D radar site (KMTX), along with meteorological surface and
      rawinsonde data, were used to identify and examine 281 eared grebe migration
      events across 15 winters from 1997/1998 through 2011/2012. An average of about 19
      migration events occurred each winter with considerable interannual variability,
      as well as large variance in the spatial area and number of birds departing the
      GSL during each event. The migration events typically occurred during clear sky
      conditions in the presence of surface high pressure and colder than average
      surface temperatures. Migration events began 55 min after sunset, on average
      across the winter seasons, and in one case we demonstrate that an extended,
      nonstop flight was initiated of the departing eared grebes to northern Mexico.
      Eared grebes leaving the GSL largely flew above the freezing level with a mean
      northerly tailwind at flight altitude of 3.1 m s-1 and a westerly, cross-flight
      wind of 5.0 m s-1 while having an average flight speed at cruising altitude of
      16.9 m s-1, or 61 km h-1. In addition to determining the variability of
      meteorological conditions during migration events across the 15 winters,
      atmospheric conditions during the largest migration event observed are presented
      and discussed.

PMID- 29043452
TI  - Spatiotemporal variability of drinking water quality and the associated health
      risks in southwestern towns of Ethiopia.
AB  - The failure to provide safe drinking water services to all people is the greatest
      development setback of the twenty-first century including Ethiopia. Potential
      pollutants from various sources are deteriorating drinking water quality in
      different seasons, and associated health risks were not clearly known. We
      determined seasonal and spatial variations of urban drinking water
      characteristics and associated health risks in Agaro, Jimma, and Metu towns,
      Southwest Ethiopia. Seventy-two samples were collected during dry and rainy
      seasons of 2014 and 2015. The majority (87.4%) of physicochemical parameters was
      found within the recommended limits. However, free residual chlorine in Jimma and
      Agaro town water sources was lower than the recommended limit and negatively
      correlated with total and fecal coliform counts (r = - 0.585 and - 0.638).
      Statistically significant differences were observed at pH, turbidity, and total
      coliform between dry and rainy seasons (p < 0.05). A Kruskal-Wallis H test
      revealed a statistically significant difference in electrical conductivity, total
      hardness, fluoride, iron, and fecal coliform across the study towns (p < 0.05).
      The Agaro town water source was the highest in fluoride concentration (3.15
      mg/l). The daily exposure level for high fluoride concentration in Agaro town was
      estimated between 0.19 and 0.41 mg/kg day, and the average cumulative hazard
      index of fluoride was > 3.13 for all age groups. Water quality variations were
      observed in all conventional water treatment systems in the rainy season, and
      further research should focus on its optimization to safeguard the public.

PMID- 29043453
TI  - Serum carbohydrate antigen 125 is a significant prognostic marker in patients
      with unresectable advanced or recurrent gastric cancer.
AB  - PURPOSE: We evaluated the diagnostic and prognostic value of three tumor markers:
      carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and
      carbohydrate antigen 125 (CA125), in the pretreatment serum of patients with
      unresectable advanced or recurrent gastric cancer. METHODS: The subjects of this
      retrospective analysis were 245 patients with unresectable advanced or recurrent
      gastric cancer diagnosed at Kochi Medical School between 2007 and 2015. We
      ascertained the sensitivity of CEA, CA19-9, and CA125 to identify a certain
      survival time and then evaluated the relative prognosis of the patients. RESULTS:
      The overall positive rates for each tumor marker in the study group were as
      follows: 57.6% (141/245) for CEA, 38.4% (94/245) for CA19-9, and 34.3% (84/245)
      for CA125; the sensitivity of these three biomarkers in combination was 73.1%
      (179/245). The median survival time of the CA125-positive patients was 4.5
      months, which was significantly shorter than that of a normal range group (18.3
      months, P < 0.001). Multivariate survival analysis identified that high CA125 was
      independently associated with a worse prognosis (HR 3.941; 95% CI 2.544-6.106; P
      < 0.001). CONCLUSIONS: Pretreatment serum CA125 is a useful prognostic biomarker
      in patients with unresectable advanced or recurrent gastric cancer. Evaluating a
      panel of serum tumor biomarkers is a useful diagnostic tool as elevated values
      might be associated with poor survival.

PMID- 29043454
TI  - A fluorescent oxaliplatin derivative for investigation of oxaliplatin resistance
      using imaging techniques.
AB  - Oxaliplatin is the backbone of chemotherapy for advanced colorectal cancer and
      undergoes clinical trials for treatment of other tumour entities. However,
      acquired resistance is a major hurdle. Confocal microscopy is a useful tool to
      get an insight into the mechanisms of resistance but it requires fluorescent
      compounds. This work describes the synthesis of the novel oxaliplatin derivative
      (CFDA-oxPt) featuring 5(6)-carboxyfluorescein diacetate and evaluation of its
      applicability for the investigation of oxaliplatin resistance using imaging
      techniques. CFDA-oxPt was somewhat less cytotoxic than oxaliplatin in sensitive
      colorectal cancer cells, with EC50 values of 26 and 5.8 uM, respectively.
      Nevertheless, the potency of the novel complex was significantly decreased to the
      EC50 of 711.2 uM in oxaliplatin-resistant cells, as was the case for oxaliplatin
      (EC50 = 81 uM). After incubation, both nuclear and cytosolic localisation was
      observed. Over time CFDA-oxPt concentrated near the cell membrane and in the
      vesicular structures, in contrast to the platinum-free label, which was rapidly
      excreted. These findings suggest that CFDA-oxPt can be used to study oxaliplatin
      resistance and open the route to new fluorophore-tethered oxaliplatin
      derivatives.

PMID- 29043455
TI  - Correction to:The innervation of extensor hallucis longus muscle: an anatomical
      study for selective neurotomy.
AB  - The original version of this article unfortunately contained mistakes. The names
      of all authors are inadvertently inverted and are now corrected in the
      authorgroup of this article.

PMID- 29043456
TI  - Correction to:"Careful" reprogramming of baclofen intrathecal programmable
      synchromed infusion pumps at their replacement in a series of 156 patients.
AB  - The original version of this article unfortunately contained mistakes. The names
      of all authors are inadvertently inverted and are now corrected in the
      authorgroup of this article.

PMID- 29043457
TI  - A 15-year analysis of the publications in the field of osteoporosis.

PMID- 29043458
TI  - Determination of acidic non-steroidal anti-inflammatory drugs in aquatic samples
      by liquid chromatography-triple quadrupole mass spectrometry combined with carbon
      nanotubes-based solid-phase extraction.
AB  - A solid-phase extraction (SPE) method based on multi-walled carbon nanotubes
      (CNT) was developed for the determination of 12 acidic non-steroidal anti
      inflammatory drugs (NSAIDs) in surface waters and tap water. Pristine and
      functionalised CNTs were evaluated as sorbent materials. Batch experiments were
      used to optimise sorption and desorption conditions (sorbent type and amount,
      adsorption time, pH). The adsorption equilibrium was reached after 8 to 48 h
      duration, which increased with the pH of solution. Non-agglomerated pristine CNTs
      (20 mg) showed the most optimal adsorption (94 to 100%) for all of the analytes
      after a 30-min contact period in acidified water solutions (100 mL). The
      compounds retained at those conditions were recovered by 40 to 95% by using 5%
      ammonium hydroxide in methanol as the desorbing solution at ambient conditions. A
      comprehensive liquid chromatography coupled to triple quadrupole mass
      spectrometry (LC-QqQ-MS/MS) was used for the analysis of real water samples. The
      method showed sufficient recovery (65-125%) and good precision (2-14% relative
      standard deviation (RSD)). The limits of detection and quantification ranged
      between 0.01 and 1.3 ng L-1 and 0.04 and 3.9 ng L-1. Only diclofenac and
      ibuprofen were found in the analysed surface water samples from Latvia (n = 10)
      and Norway (n = 14). Diclofenac was found at 1.7-8.4 ng L-1 concentration in two
      samples of surface waters, whereas the concentrations of ibuprofen ranged between
      1.0 and 9.2 ng L-1 in seven samples collected in Norway and 3.9-17 ng L-1 in
      three samples from Latvia.

PMID- 29043459
TI  - Mobility of Pb, Zn, Cu and As in disturbed forest soils affected by acid rain.
AB  - Early efforts at remediation of contaminated soils involve overturn or removal of
      the uppermost soil horizons. We find that such disruption is counterproductive,
      as it actually increases the mobility of the heavy metals involved. In our study,
      we sought to replicate in a controlled manner this commonly used remediation
      strategy and measure Pb, Zn, Cu and As concentrations in all soil horizons-both
      prior to and 1 year after disruption by trenching. BCR analyses (sequential
      leaching) indicate that Pb is affected to the greatest degree and is most highly
      mobile; however, Zn and As remain insoluble, thus partially ameliorating the
      detrimental effect. Differences in vegetation cover (i.e. spruce vs. beech
      forest) have little influence on overall element mobility patterns. The Krusne
      hory (Ore Mts., Czech Republic) study area is one of the more heavily
      contaminated areas in Central Europe, and thus the results reported here are
      applicable to areas affected by brown-coal-burning power plants.

PMID- 29043460
TI  - Longitudinal assessment of the impact of adapted physical activity on upper limb
      disability and quality of life in breast cancer survivors from an Italian cohort.
AB  - PURPOSE: The purpose of this study was to evaluate the effectiveness of a
      specific adapted physical activity (APA) protocol on upper limb disability and
      quality of life in breast cancer survivors and to assess longitudinally the
      possible role of APA on long-term benefits. METHODS: Breast cancer survivors from
      an Italian cohort were assessed by fitness tests (shoulder-arm mobility, range of
      motion, and back flexibility) before and after 8-week APA. Quality of life and
      back and surgical shoulder pain intensity were evaluated by Short Form-12 and
      numerical rating scale questionnaires, respectively. At 1.5-year post-APA follow
      up, survivors were evaluated as at baseline/post-APA to assess long-term effects.
      RESULTS: A statistically significant improvement in shoulder-arm mobility, pain
      perception, and quality of life was observed in breast cancer survivors after APA
      intervention. Longitudinal analyses indicated an overall decrease in the achieved
      benefits at 1.5-year post-APA. CONCLUSIONS: The survivorship phase of breast
      cancer requires a multidisciplinary collaboration involving either the cancer
      care medical team or APA professionals to manage psychophysical outcomes. A
      specific APA protocol may represent an effective countermeasure to reduce post
      treatment upper limb disability and improve the quality of life in breast cancer
      survivors. Participation in structured APA protocols should be maintained over
      time to preserve the achieved benefits.

PMID- 29043462
TI  - An experimental model to measure the ability of headphones with active noise
      control to reduce patient's exposure to noise in an intensive care unit.
AB  - BACKGROUND: Defining the association between excessive noise in intensive care
      units, sleep disturbance and morbidity, including delirium, is confounded by the
      difficulty of implementing successful strategies to reduce patient's exposure to
      noise. Active noise control devices may prove to be useful adjuncts but there is
      currently little to quantify their ability to reduce noise in this complex
      environment. METHODS: Sound meters were embedded in the auditory meatus of three
      polystyrene model heads with no headphones (control), with headphones alone and
      with headphones using active noise control and placed in patient bays in a
      cardiac ICU. Ten days of recording sound levels at a frequency of 1 Hz were
      performed, and the noise levels in each group were compared using repeated
      measures MANOVA and subsequent pairwise testing. RESULTS: Multivariate testing
      demonstrated that there is a significant difference in the mean noise exposure
      levels between the three groups (p < 0.001). Subsequent pairwise testing between
      the three groups shows that the reduction in noise is greatest with headphones
      and active noise control. The mean reduction in noise exposure between the
      control and this group over 24 h is 6.8 (0.66) dB. The use of active noise
      control was also associated with a reduction in the exposure to high-intensity
      sound events over the course of the day. CONCLUSIONS: The use of active noise
      cancellation, as delivered by noise-cancelling headphones, is associated with a
      significant reduction in noise exposure in our model of noise exposure in a
      cardiac ICU. This is the first study to look at the potential effectiveness of
      active noise control in adult patients in an intensive care environment and shows
      that active noise control is a candidate technology to reduce noise exposure
      levels the patients experience during stays on intensive care.

PMID- 29043461
TI  - Effect of anti-angiogenesis induced by chemotherapeutic monotherapy,
      chemotherapeutic/bisphosphonate combination therapy and anti-VEGFA mAb therapy on
      tooth extraction socket healing in mice.
AB  - Osteonecrosis of the jaw (ONJ), which is a rare but severe adverse effect, mainly
      occurs in oncology patients receiving chemotherapeutic agents and
      bisphosphonates. However, the combined impact of chemotherapy and bisphosphonates
      on wound healing after tooth extraction remains unknown. The aim of this study
      was to determine the precise etiology of ONJ induced by chemotherapy and
      bisphosphonate combination therapy. Mice received zoledronate (ZA) monotherapy,
      cyclophosphamide (CY) monotherapy or CY/ZA combination therapy. The maxillary
      first molars were extracted 3 weeks after the initiation of drug treatment.
      Moreover, antivascular endothelial growth factor A (VEGFA) monoclonal antibody
      (mAb) was administered once every 2 days just after tooth extraction for 2 weeks.
      Soft and hard tissue wound healing was evaluated 2 and 4 weeks post-extraction
      using histomorphometry, microcomputed tomography and immunohistochemistry. ZA
      monotherapy did not induce impaired oral wound healing and ONJ-like lesions 2 and
      4 weeks post-extraction, respectively. Tooth extraction socket healing worsened
      with severe anti-angiogenesis by CY monotherapy and CY/ZA combination therapy 2
      weeks post-extraction. However, CY monotherapy rarely induced ONJ-like lesions
      with severe angiogenesis suppression, whereas CY/ZA combination therapy
      frequently induced ONJ-like lesions with severe angiogenesis inhibition 4 weeks
      post-extraction. Interestingly, anti-VEGFA mAb therapy delayed osseous wound
      healing with normal soft tissue wound healing of tooth extraction sockets,
      although this therapy significantly suppressed blood vessel formation. Our
      findings suggest that anti-angiogenesis alone is not the main cause of ONJ-like
      lesions induced by CY/ZA combination therapy. The combination of suppressed
      osteoclasts and anti-angiogenesis, in addition to other risk factors such as
      chemotherapy, may contribute to the development of ONJ.

PMID- 29043463
TI  - Serum selenium levels predict survival after breast cancer.
AB  - BACKGROUND: Studies have reported an inverse relationship between serum selenium
      levels and cancer incidence, but the impact of low serum selenium status on
      survival after a diagnosis of breast cancer has not been established. METHODS: We
      obtained a blood sample from 546 women diagnosed with a first primary invasive
      breast cancer between 2008 and 2015 in the region of Szczecin, Poland. Blood was
      collected after diagnosis, but prior to treatment. Serum selenium was quantified
      by mass spectroscopy and each patient was assigned to one of four categories
      (quartiles) based on the distribution in the entire cohort. Patients were
      followed from diagnosis to death over a mean follow-up of 3.8 years. Vital status
      was obtained by linkage to the Polish National Death Registry. RESULTS: The 5
      year overall actuarial survival was 68.1% for women in the lowest (< 64.4 ug/L)
      and 82.5% for those in the highest (> 81.0 ug/L) quartile of serum selenium. In
      an adjusted analysis, the hazard ratio for death was 2.49 (95%CI 1.53-4.04; P =
      0.0002) for patients in the lowest quartile of serum selenium, compared to those
      in all other quartiles. The effect of low selenium on breast cancer-specific
      mortality was stronger for women who were past smokers (HR 6.03; 95%CI 1.96-18.6;
      P = 0.0002). CONCLUSIONS: This study suggests that a selenium level in excess of
      64.4 ug//L might be beneficial for women undergoing treatment for breast cancer
      and that selenium supplementation to achieve this level may favorably impact the
      outcome. Further studies are needed to confirm this association and to evaluate
      the impact of selenium supplementation on breast cancer survival among women with
      low post-diagnostic selenium levels.

PMID- 29043464
TI  - The importance of early detection of calcifications associated with breast cancer
      in screening.
AB  - PURPOSE: The aim of this study was to assess how often women with undetected
      calcifications in prior screening mammograms are subsequently diagnosed with
      invasive cancer. METHODS: From a screening cohort of 63,895 women, exams were
      collected from 59,690 women without any abnormalities, 744 women with a screen
      detected cancer and a prior negative exam, 781 women with a false positive exam
      based on calcifications, and 413 women with an interval cancer. A radiologist
      identified cancer-related calcifications, selected by a computer-aided detection
      system, on mammograms taken prior to screen-detected or interval cancer
      diagnoses. Using this ground truth and the pathology reports, the sensitivity for
      calcification detection and the proportion of lesions with visible calcifications
      that developed into invasive cancer were determined. RESULTS: The screening
      sensitivity for calcifications was 45.5%, at a specificity of 99.5%. A total of
      68.4% (n = 177) of cancer-related calcifications that could have been detected
      earlier were associated with invasive cancer when diagnosed. CONCLUSIONS:
      Screening sensitivity for detection of malignant calcifications is low. Improving
      the detection of these early signs of cancer is important, because the majority
      of lesions with detectable calcifications that are not recalled immediately but
      detected as interval cancer or in the next screening round are invasive at the
      time of diagnosis.

PMID- 29043466
TI  - Innovation at the Intersection of Alcohol and HIV Research.
AB  - Working in an interdisciplinary manner at the crossroads of alcohol and HIV
      research is a challenge. This paper presents six novel approaches that could be
      applied to activities at the intersection of alcohol and HIV. These approaches
      are (i) address the fact that the availability of new technology is unevenly
      distributed around the world, (ii) use technology to move beyond both paper and
      digital surveys, (iii) introduce a focus on advocacy and partnerships with large
      technology companies, (iv) harness technological innovation to utilise digital
      counselling, (v) explore the use of virtual reality in both research and
      delivering interventions, and (vi) consider alternative funding models to those
      currently in existence to improve efficiencies and innovations. Aiming to
      understand the interplay of alcohol and HIV will require creativity. The six
      approaches outlines in this paper provide possible directions from which new
      approaches may emerge.

PMID- 29043465
TI  - Comparison of strain imaging techniques in CRT candidates: CMR tagging, CMR
      feature tracking and speckle tracking echocardiography.
AB  - Parameters using myocardial strain analysis may predict response to cardiac
      resynchronization therapy (CRT). As the agreement between currently available
      strain imaging modalities is unknown, three different modalities were compared.
      Twenty-seven CRT-candidates, prospectively included in the MARC study, underwent
      cardiac magnetic resonance (CMR) imaging and echocardiographic examination. Left
      ventricular (LV) circumferential strain was analysed with CMR tagging (CMR-TAG),
      CMR feature tracking (CMR-FT), and speckle tracking echocardiography (STE). Basic
      strain values and parameters of dyssynchrony and discoordination obtained with
      CMR-FT and STE were compared to CMR-TAG. Agreement of CMR-FT and CMR-TAG was
      overall fair, while agreement between STE and CMR-TAG was often poor. For both
      comparisons, agreement on discoordination parameters was highest, followed by
      dyssynchrony and basic strain parameters. For discoordination parameters,
      agreement on systolic stretch index was highest, with fair intra-class
      correlation coefficients (ICC) (CMR-FT: 0.58, STE: 0.55). ICC of septal systolic
      rebound stretch (SRSsept) was poor (CMR-FT: 0.41, STE: 0.30). Internal stretch
      factor of septal and lateral wall (ISFsep-lat) showed fair ICC values (CMR-FT:
      0.53, STE: 0.46), while the ICC of the total LV (ISFLV) was fair for CMR-FT
      (0.55) and poor for STE (ICC: 0.32). The CURE index had a fair ICC for both
      comparisons (CMR-FT: 0.49, STE 0.41). Although comparison of STE to CMR-TAG was
      limited by methodological differences, agreement between CMR-FT and CMR-TAG was
      overall higher compared to STE and CMR-TAG. CMR-FT is a potential clinical
      alternative for CMR-TAG and STE, especially in the detection of discoordination
      in CRT-candidates.

PMID- 29043467
TI  - Do Subjective Alcohol Screening Tools Correlate with Biomarkers Among High-Risk
      Transgender Women and Men Who Have Sex with Men in Lima, Peru?
AB  - Alcohol abuse can influence sexual risk behavior; however, its measurement is not
      straightforward. This study compared self-reported alcohol use, via the AUDIT and
      CAGE, with levels of phosphatidylethanol (Peth), a phospholipid biomarker that
      forms with chronic, heavy drinking, among high-risk MSM and TW in Lima, Peru. Chi
      square, Fisher's exact, Wilcoxon ranksum tests compared the instruments. Receiver
      operating curves determined sensitivity and specificity of the self-reported
      measures. Among 69 MSM and 17 TW, PEth was positive for 86% (95% CI 77-93%) of
      participants, while 67% reported binge-drinking in the last 2 weeks. The AUDIT
      classified 25% as hazardous drinkers while CAGE identified 6% as problem
      drinkers. Self-reported binge drinking was more sensitive than the AUDIT for PEth
      positivity (71% vs. 27%, p = 0.022). Among high-risk MSM and TW in Lima,
      validated, self-report measures of alcohol abuse underestimated biological
      measures. Further research correlating bio-markers and self-reported alcohol
      abuse measures is needed.

PMID- 29043469
TI  - E3 ubiquitin ligases in cancer and implications for therapies.
AB  - E3 ligases are a class of enzymes that can transfer ubiquitin to substrates for
      their degradation, which are of importance in cellular homeostasis. Since many
      oncogenic or tumor-suppressive proteins are reported to be regulated by the
      ubiquitin-proteasome system (UPS), E3 ligases, which function as substrate
      interacting modules, have been attracting more and more attention as promising
      anticancer drug targets due to their pivotal role in conferring substrate
      specificity. Generally, based on their molecular structure and functional
      mechanism, E3 ligases can be divided into three major types: homologous to E6
      associated protein C-terminus (HECT), really interesting new gene (RING), and
      RING-in-between-RING (RBR) E3 ligases. Based on the significance of their
      functions, more bioactive compounds targeting E3 ligases should be developed in
      the future. In this review, we discuss the important roles of E3 ligases involved
      in cancer as well as available bioactive compounds targeting various E3 ligases
      for potential anticancer activity.

PMID- 29043468
TI  - Cognitive and behavioral disorders in Parkinson's disease: an update. I:
      cognitive impairments.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disease characterized
      by motor symptoms such as rigidity, rest tremor, and bradykinesia. However, a
      growing body of evidence demonstrated that PD encompasses several non-motor
      disturbances as well, such as cognitive impairment. Cognitive defects can be
      present since early stages of the disease but tend to dominate the clinical
      picture as the disease progresses. Around 40% of patients with PD present with
      cognitive impairments in several cognitive domains including attention, working
      memory and executive functions, language, visuospatial skills, and episodic
      memory; in later stages of the disease, cognitive defects and associated
      behavioral disorders concur to determine clinically relevant PD-associated
      dementia. Part of these defects is ascribed to a dopamine-dependent dysfunction
      of fronto-striatal pathways, but there is a considerable heterogeneity in the
      cognitive impairments as well as a suggestion of the role of other
      neurotransmitter systems, such as the cholinergic one, mainly responsible for
      Parkinson-dementia syndrome. In this paper, we review recent literature with
      particular attention to the last 5 years on the main cognitive deficits described
      in PD patients as well as on the hypothesized neuro-functional substrate of such
      impairments. Finally, we provide some suggestions on how to test cognitive
      functions in PD appropriately.

PMID- 29043470
TI  - Comprehensive analysis of NMR data using advanced line shape fitting.
AB  - NMR spectroscopy is uniquely suited for atomic resolution studies of biomolecules
      such as proteins, nucleic acids and metabolites, since detailed information on
      structure and dynamics are encoded in positions and line shapes of peaks in NMR
      spectra. Unfortunately, accurate determination of these parameters is often
      complicated and time consuming, in part due to the need for different software at
      the various analysis steps and for validating the results. Here, we present an
      integrated, cross-platform and open-source software that is significantly more
      versatile than the typical line shape fitting application. The software is a
      completely redesigned version of PINT ( https://pint-nmr.github.io/PINT/ ). It
      features a graphical user interface and includes functionality for peak picking,
      editing of peak lists and line shape fitting. In addition, the obtained peak
      intensities can be used directly to extract, for instance, relaxation rates,
      heteronuclear NOE values and exchange parameters. In contrast to most available
      software the entire process from spectral visualization to preparation of
      publication-ready figures is done solely using PINT and often within minutes,
      thereby, increasing productivity for users of all experience levels. Unique to
      the software are also the outstanding tools for evaluating the quality of the
      fitting results and extensive, but easy-to-use, customization of the fitting
      protocol and graphical output. In this communication, we describe the features of
      the new version of PINT and benchmark its performance.

PMID- 29043471
TI  - Nanostructured Lipid Carrier Co-loaded with Doxorubicin and Docosahexaenoic Acid
      as a Theranostic Agent: Evaluation of Biodistribution and Antitumor Activity in
      Experimental Model.
AB  - PURPOSE: Nanotheranostic platforms, i.e., the combination of both therapeutic and
      diagnostic agents on a single platform, are emerging as an interesting tool for
      the personalized cancer medicine. Therefore, the aim of this work was to evaluate
      the in vivo properties of a Tc-99m-labeled nanostructured lipid carrier (NLC)
      formulation, co-loaded with doxorubicin (DOX) and docosahexaenoic acid (DHA), for
      theranostic applications. PROCEDURES: NLC-DHA-DOX were prepared busing the hot
      melting homogenization method using an emulsification-ultrasound and were
      radiolabeled with Tc-99m. Biodistribution studies, scintigraphic images, and
      antitumor activity were performed in 4T1 tumor-bearing mice. RESULTS: NCL was
      successfully radiolabeled with Tc-99m. Blood clearance showed a relatively long
      half-life, with blood levels decaying in a biphasic manner (T1/2 alpha = 38.7
      min; T1/2 beta = 516.5 min). The biodistribution profile and scintigraphic images
      showed higher tumor uptake compared to contralateral muscle in all time-points
      investigated. Antitumor activity studies showed a substantial tumor growth
      inhibition ratio for NLC-DHA-DOX formulation. In addition, the formulation showed
      more favorable toxicity profiles when compared to equivalent doses of free
      administered drugs, being able to reduce heart and liver damage. CONCLUSIONS:
      Therefore, NLC-DHA-DOX formulation demonstrated feasibility in breast cancer
      treatment and diagnosis/monitoring, leading to a new possibility of a theranostic
      platform.

PMID- 29043472
TI  - Biotoxicity of Cry1Ab protein on wolf spider Pardosa pseudoannulata.
AB  - In this research, we carried out a tritrophic bioassay to assess the potential
      effect of Cry1Ab-expressing rice on the foraging behavior of the common wolf
      spider Pardosa pseudoannulata and its underlying molecular mechanism. Results
      indicated the Bt-containing spiders expressed a higher foraging range when
      compared to controls. The high throughput de novo transcriptome sequencing was
      further carried out for central nervous system (CNS) of P. pseudoannulata with
      and without Cry1Ab intake. We obtained 120, 985 unigenes with a mean length of
      529.73 bp. Functional analysis of differentially expressed genes (DEGs) showed
      the expression levels of genes related to energy metabolism were changed in
      response to Cry1Ab, which may contribute to a more active foraging behavior. In
      addition, some DEGs also have a function related to metal ion binding, implying a
      potential influence on metal ions-dependent reactions. This may be associated
      with Cry1Ab resistance mechanism in the spider.

PMID- 29043473
TI  - Investigating long-term effect of nanoparticles on growth of Raphanus sativus
      plants: a trans-generational study.
AB  - In the past decade, there has been an unprecedented growth in the application of
      nanoparticles (NPs) worldwide. Even though the acute toxicity of CuO and ZnO NPs
      to plants has been investigated in past, the trans-generational effects of these
      NPs in the environment are still unknown. In this study, we investigated whether
      the treatment of radish plants with CuO and ZnO NPs as single compound and as a
      binary mixture (10, 100 and 1000 mg/Kg soil) through their lifecycle would affect
      the seed quality and the development of second-generation seedlings or not.
      Results showed reduced root length, shoot length and biomass in F1 seedlings of
      NPs treated plants. The treated F1 seeds had smaller seed weight with accumulated
      Cu and Zn. The effect of toxic interaction between CuO and ZnO on plant growth
      was antagonistic in nature. Evaluation of the trans-generational impact is
      important to understand the long-term effect of NPs on the environment.

PMID- 29043474
TI  - Genetic diversity of Afrikaner cattle in southern Africa.
AB  - The Afrikaner is an indigenous South African breed of "Sanga" type beef cattle
      along with breeds such as the Drakensberger and Nguni. Six composite breeds have
      been developed from crosses with the Afrikaner. Additionally, Afrikaner has been
      the base from which exotic breeds were established in South Africa through
      backcrossing. The study examined genetic diversity of Afrikaner cattle by
      genotyping 1257 animals from 27 herds in different geographic areas of South
      Africa and Namibia using 11 microsatellite markers. Multiple-locus assignment,
      performed using the Bayesian clustering algorithm of STRUCTURE, revealed three
      underlying genotypic groups. These groups were not geographically localized.
      Across herds and markers, the proportion of unbiased heterozygosity ranged from
      0.49 to 0.72 averaging 0.57; mean number of alleles per locus ranged from 3.18 to
      7.09, averaging 4.81; and allelic richness ranged from 2.35 to 3.38, averaging
      2.67. It is concluded that a low inbreeding level of 2.7% and a moderate to high
      degree of variation still persists within the Afrikaner cattle breed, despite the
      recent decline in numbers of animals.

PMID- 29043475
TI  - Calculation of indirect costs of associated with postoperative caregiver absences
      after pediatric tonsil surgery.

PMID- 29043476
TI  - Drug-Induced Sedation Endoscopy (DISE) DATA FUSION system: clinical feasibility
      study.
AB  - Drug-induced sleep endoscopy (DISE) is a diagnostic technique for 3D dynamic
      anatomical visualisation of upper airway obstruction during sedated sleep. There
      is a lack of standardised procedure and objective measurement associated with
      information capture, information management, evaluation of DISE findings,
      treatment planning, and treatment outcomes. The objective of this study is to
      present clinical feasibility results using a DISE DATA FUSION system for
      capturing, merging, displaying and storing anatomical data from an endoscopic
      imaging system and cardiorespiratory data from an anaesthesiological monitoring
      system simultaneously in real-time during DISE. This prospective cohort study
      included 20 patients presenting with symptoms of sleep related breathing
      disorders undergoing drug-induced sedation endoscopy and had volunteered for DISE
      DATA FUSION system to be used during their DISE assessment. The DISE DATA FUSION
      system was used to capture, merge, display, and store anatomical changes from an
      endoscopic imaging system and cardiorespiratory changes from an
      anaesthesiological monitoring system simultaneously in real time during drug
      induced sedation endoscopy assessment. In all 20 patients, anatomical
      obstructions at different levels of the pharyngeal lumen (soft palate, velum,
      tonsils, oropharynx lateral wall, base of tongue, and epiglottis) with a
      different obstruction configuration and severity were captured simultaneously in
      real time with its associated cardiorespiratory parameters. Furthermore, a
      composite video consisting of an anatomical image, blood oxygen level, pulse
      rate, blood pressure, and timestamp was created for every obstructive event. Our
      system provides a useful and better way of capturing, merging, visualising, and
      storing anatomical data/physiological data simultaneously during DISE in real
      time. Furthermore, it enhances the understanding of the impact of the anatomical
      severity due to the simultaneous display of the cardiovascular parameters at that
      specific time of anatomical obstruction for optimising surgical decision based on
      DISE.

PMID- 29043477
TI  - Laryngopharyngeal reflux is a potential cause of nasal congestion and obstructive
      sleep apnea syndrome.

PMID- 29043478
TI  - The compensatory enlargement of the remaining thyroid lobe following
      hemithyroidectomy is small and without impact on symptom relief.
AB  - According to previous studies, hemithyroidectomy results in growth of the
      remaining thyroid lobe by up to 30% in first 12 months after surgery. However,
      this estimate is based on imprecise methods, high inter- and intra-observer
      variability, and lack of blinding of the measurements. Furthermore, it is unknown
      whether enlargement of the remaining hemi-thyroid interferes with the improvement
      in symptoms after surgery for goiter. We aimed to assess the impact of
      postoperative thyroid growth on goiter symptom relief following hemithyroidectomy
      in patients with benign nodular goiter. Outcomes were measured before and 6
      months after hemithyroidectomy in 44 patients. Thyroid volumes were determined by
      two independent and blinded observers using magnetic resonance imaging (MRI).
      Inter- and intra-observer variability was visualized by Bland-Altman plots.
      Goiter symptoms were assessed by the Thyroid-Specific Patient-Reported-Outcome
      Questionnaire (ThyPRO) on a scale from 0 to 100 points. After hemithyroidectomy,
      the remaining thyroid lobe was 13.7 +/- 6.4 mL, and enlarged by a mean of 1.8 mL
      over 6 months [95% confidence interval (CI) (1.6; 2.1), p < 0.001], corresponding
      to an increase of 17% [95% CI (12; 22)]. The Goiter Symptom score improved by 27
      points [95% CI (21; 34), p < 0.0001] from median 39 points (range 2-86) at
      baseline, and was unaffected by the compensatory thyroid growth. Six months after
      hemithyroidectomy, using blinded MRI evaluations, we demonstrated a small but
      significant postoperative growth of the remaining hemi-thyroid, which did not
      significantly affect the considerable improvement in goiter symptoms.

PMID- 29043479
TI  - Altered auditory and vestibular functioning in individuals with low bone mineral
      density: a systematic review.
AB  - Alteration in the process of bone remodelling is associated with falls and
      fractures due to increased bone fragility and altered calcium functioning. The
      auditory system consists of skeletal structures and is, therefore, prone to
      getting affected by altered bone remodelling. In addition, the vestibule consists
      of huge volumes of calcium (CaCO3) in the form of otoconia crystals and
      alteration in functioning calcium levels could, therefore, result in vestibular
      symptoms. Thus, the present study aimed at compiling information from various
      studies on assessment of auditory or vestibular systems in individuals with
      reduced bone mineral density (BMD). A total of 1977 articles were searched using
      various databases and 19 full-length articles which reported auditory and
      vestibular outcomes in persons with low BMD were reviewed. An intricate
      relationship between altered BMD and audio-vestibular function was evident from
      the studies; nonetheless, how one aspect of hearing or balance affects the other
      is not clear. Significant effect of reduced bone mineral density could probably
      be due to the metabolic changes at the level of cochlea, secondary to alterations
      in BMD. One could also conclude that sympathetic remodelling is associated with
      vestibular problems in individual; however, whether vestibular problems lead to
      altered BMD cannot be ascertained with confidence. The studies reviewed in the
      article provide an evidence of possible involvement of hearing and vestibular
      system abnormalities in individuals with reduced bone mineral density. Hence, the
      assessment protocol for these individuals must include hearing and balance
      evaluation as mandatory for planning appropriate management.

PMID- 29043480
TI  - Body mass index (BMI), postoperative appearance satisfaction, and sexual function
      in breast cancer survivorship.
AB  - PURPOSE: We sought to explore the correlation between BMI and postoperative
      sexual function, body image, and breast-specific sensuality before and after
      breast cancer surgery. METHODS: A cross-sectional survey of patients at least 1
      year from surgery employed the Female Sexual Function Index (FSFI) and
      investigator-generated questions. Patients who underwent lumpectomy (L),
      mastectomy (M), and mastectomy with reconstruction (MR) were compared across
      three BMI groups: normal weight, overweight, and obese. RESULTS: Two hundred
      fifty-five patients underwent lumpectomy (L, n = 174), mastectomy (M, n = 22), or
      mastectomy with reconstruction (MR, n = 59). Median age was 57 (range 30-93) and
      median BMI was 28 (range 19-45). Obese and overweight women reported more
      appearance dissatisfaction (18.1 and 13.0%) than normal weight women (4.1%) (p =
      0.01). Lower satisfaction was associated with increasing BMI within the MR group
      (p = 0.05). The obese group's median FSFI score met criteria for sexual
      dysfunction (25.90, range 11.30-33.10). More overweight women reported their
      chest played an important role in intimacy before and after surgery, but a
      postoperative decline in the importance of this role was observed in all groups.
      CONCLUSIONS: Greater post-treatment BMI is inversely related to postoperative
      appearance satisfaction, particularly in those undergoing mastectomy with
      reconstruction. The role of the breast in intimacy is greatest in overweight
      women, but decreases postoperatively in all BMI groups. IMPLICATIONS FOR CANCER
      SURVIVORS: Postoperative appearance satisfaction and sexual function seems to be
      correlated to post-treatment BMI, which highlights the need to encourage
      perioperative weight management for improved survivorship outcomes.

PMID- 29043481
TI  - Irish Thoracic Society Annual Scientific Meeting 2017 10th - 11th November 2017,
      Limerick Strand Hotel, Limerick.

PMID- 29043482
TI  - Assessing the Role of Gambling on Problematic Alcohol Consumption by Police
      Officers.
AB  - While a number of studies have attributed critical incident stressors to alcohol
      abuse among police officers, no study has examined the role gambling, if any,
      plays on problematic alcohol consumption. Therefore, data from the Police Stress
      and Domestic Violence in Police Families in Baltimore, Maryland, 1997-1999 are
      analyzed to test the influence of gambling on problematic alcohol consumption
      engaged by police officers. Results indicated that gambling is significant in
      predicting problematic alcohol consumption. Burnout, peer drinking, and self
      control also predicted the dependent variable. The study's results, as well as
      the study's limitations and directions for future research, are also discussed.

PMID- 29043483
TI  - Iron toxicity in yeast: transcriptional regulation of the vacuolar iron importer
      Ccc1.
AB  - All eukaryotes require the transition metal, iron, a redox active element that is
      an essential cofactor in many metabolic pathways, as well as an oxygen carrier.
      Iron can also react to generate oxygen radicals such as hydroxyl radicals and
      superoxide anions, which are highly toxic to cells. Therefore, organisms have
      developed intricate mechanisms to acquire iron as well as to protect themselves
      from the toxic effects of excess iron. In fungi and plants, iron is stored in the
      vacuole as a protective mechanism against iron toxicity. Iron storage in the
      vacuole is mediated predominantly by the vacuolar metal importer Ccc1 in yeast
      and the homologous transporter VIT1 in plants. Transcription of yeast CCC1
      expression is tightly controlled primarily by the transcription factor Yap5,
      which sits on the CCC1 promoter and activates transcription through the binding
      of Fe-S clusters. A second mechanism that regulates CCC1 transcription is through
      the Snf1 signaling pathway involved in low-glucose sensing. Snf1 activates stress
      transcription factors Msn2 and Msn4 to mediate CCC1 transcription.
      Transcriptional regulation by Yap5 and Snf1 are completely independent and
      provide for a graded response in Ccc1 expression. The identification of multiple
      independent transcriptional pathways that regulate the levels of Ccc1 under high
      iron conditions accentuates the importance of protecting cells from the toxic
      effects of high iron.

PMID- 29043484
TI  - The role of yeast m6A methyltransferase in peroxisomal fatty acid oxidation.
AB  - The precise and controlled regulation of gene expression at transcriptional and
      post-transcriptional levels is crucial for the eukaryotic cell survival and
      functions. In eukaryotes, more than 100 types of post-transcriptional RNA
      modifications have been identified. The N6-methyladenosine (m6A) modification in
      mRNA is among the most common post-transcriptional RNA modifications known in
      eukaryotic organisms, and the m6A RNA modification can regulate gene expression.
      The role of yeast m6A methyltransferase (Ime4) in meiosis, sporulation,
      triacylglycerol metabolism, vacuolar morphology, and mitochondrial functions has
      been reported. Stress triggers triacylglycerol accumulation as lipid droplets.
      Lipid droplets are physically connected to the different organelles such as
      endoplasmic reticulum, mitochondria, and peroxisomes. However, the physiological
      relevance of these physical interactions remains poorly understood. In yeast,
      peroxisome is the sole site of fatty acid beta-oxidation. The metabolic status of
      the cell readily governs the number and physiological function of peroxisomes.
      Under low-glucose or stationary-phase conditions, peroxisome biogenesis and
      proliferation increase in the cells. Therefore, we hypothesized a possible role
      of Ime4 in the peroxisomal functions. There is no report on the role of Ime4 in
      peroxisomal biology. Here, we report that IME4 gene deletion causes peroxisomal
      dysfunction under stationary-phase conditions in Saccharomyces cerevisiae;
      besides, the ime4Delta cells showed a significant decrease in the expression of
      the key genes involved in peroxisomal beta-oxidation compared to the wild-type
      cells. Therefore, identification and determination of the target genes of Ime4
      that are directly involved in the peroxisomal biogenesis, morphology, and
      functions will pave the way to better understand the role of m6A methylation in
      peroxisomal biology.

PMID- 29043485
TI  - Nitrate assimilation pathway (NAP): role of structural (nit) and transporter
      (ntr1) genes in Fusarium oxysporum f.sp. lycopersici growth and pathogenicity.
AB  - The tomato pathogen Fusarium oxysporum f.sp. lycopersici possesses the capability
      to use nitrate as the only nitrogen source under aerobic and anaerobic conditions
      and to activate virulence-related functions when cultivated in the presence of
      nitrate, but not in ammonium. The genome of F. oxysporum f.sp. lycopersici
      encodes three paralogs nitrate reductase (NR) genes (nit1, nit2 and nit3) and one
      predicted ortholog of the Aspergillus nidulans high-affinity nitrate/nitrite
      transporters NtrA and NtrB, named ntr1. We set out to clarify the role of nit1,
      nit2, nit3 and ntr1 genes in nitrate assimilation and in the virulence of F.
      oxysporum f.sp. lycopersici. Quantitative RT-PCR analysis revealed that only
      nit1, nit2 and ntr1 are expressed at significant levels during growth in nitrate
      as the only nitrogen source. Targeted deletion of nit1 and ntr1, but not of nit2
      or nit3, severely impaired growth of F. oxysporum on nitrate as nitrogen source,
      indicating that Nit1 and Ntr1 proteins are involved in nitrate assimilation by
      the fungus; biochemical analysis of nit mutants indicated that Nit1 and Nit2
      enzymes contribute to about 50 and 30% of the total NR activity, respectively. In
      addition, a spontaneous chlorate-resistant mutant derived from F. oxysporum 4287,
      denoted NitFG, was characterized, showing inability to grow in nitrate under
      aerobic and anaerobic conditions and low levels of NR activity, in spite of its
      increased transcription levels of nit1 and nit2 genes. Tomato plant infection
      assays showed that NitFG and ?ntr1 mutants induced an earlier death in tomato
      plants, whereas the single mutants ?nit1, ?nit2 and ?nit1?nit2 double mutant
      showed a mortality rate similar to the wild-type strain. Taken together, these
      results indicate that the Nit1 and Ntr1 proteins are important for nitrate
      assimilation of F. oxysporum f.sp. lycopersici incubated under aerobic and
      anaerobic conditions and that this metabolic process is not essential for the
      virulence of the fungus. These observations open new questions about the role of
      Nit1, Nit2, and Nit3 proteins in other routes of nitrate metabolism in this
      pathogenic fungus and in the possible regulatory role that can be exerted by the
      AreA protein in these routes.

PMID- 29043486
TI  - Study of In-Trap Ion Clouds by Ion Trajectory Simulations.
AB  - Gaussian distribution has been utilized to describe the global number density
      distribution of ion cloud in the Paul trap, which is known as the thermal
      equilibrium theory and widely used in theoretical modeling of ion clouds in the
      ion traps. Using ion trajectory simulations, however, the ion clouds can now also
      be treated as a dynamic ion flow field and the location-dependent features could
      now be characterized. This study was carried out to better understand the in-trap
      ion cloud properties, such as the local particle velocity and temperature. The
      local ion number densities were found to be heterogeneously distributed in terms
      of mean and distribution width; the velocity and temperature of the ion flow
      varied with pressure depending on the flow type of the neutral molecules; and the
      "quasi-static" equilibrium status can only be achieved after a certain number of
      collisions, for which the time period is pressure-dependent. This work provides
      new insights of the ion clouds that are globally stable but subjected to local rf
      heating and collisional cooling. Graphical Abstract ?.

PMID- 29043487
TI  - The Differences in Spirometry Predictive Equations in Classifying Presence and
      Degree of Lung Function Impairment: Which Suit Fits the Best?
AB  - PURPOSE: The aim of this study was to compare the differences between three most
      commonly used predictive equations (PE): ECCS (European Community of Coal and
      Steel), the third National Health and Nutrition Examination Survey (NHANES III),
      and GLI (Global Lung Initiative) in healthy individuals and when grading severity
      of lung function impairment in patients with obstructive lung diseases. METHODS:
      The study included 200 healthy volunteers and 200 patients with obstructive lung
      diseases at the Institute for Pulmonary Diseases of Vojvodina. In all subjects,
      we calculated the absolute and relative (percent) predicted values using ECCS,
      NHANES III, and GLI reference equations. RESULTS: The mean differences between
      ECCS and NHANES III predicted values were 5.63% (95% CI  5.29-5.98%, p < 0.001)
      for FEV1 and 10% (95% CI 9.52-10.79%, p < 0.001) for FVC. Similar differences
      were observed between ECCS and GLI predicted values. There were minimal
      differences between NHANES III and GLI predictive values. In healthy subjects,
      the mean absolute difference between measured FEV1 and FEV1 ECCS predicted was
      0.36l (95% CI 0.32l, 0.40l, p < 0.001), FEV1 NHANES predicted was 0.30 l (95% CI
      0.27-0.35l, p < 0.001), and FEV1 GLI predicted was 0.31l (95% CI 0.27- 0.35l, p <
      0.001). The use of three different PE leads to significant differences in
      classification of obstruction severity in both asthma and COPD patients.
      CONCLUSIONS: There were significant differences between FEV1 and FVC predicted
      when using different PE. The absolute difference between actual and predicted
      FEV1 in healthy individuals was highest when using ECCS. The use of different PE
      may change the interpretation of severity of airway obstruction.

PMID- 29043488
TI  - Hair analysis does not allow to discriminate between acute and chronic
      administrations of a drug in young children.
AB  - There are many differences between the hair from children and that of adult
      subjects, the hair being thinner, more porous with a different growth rate from
      the usual 1 cm/month observed in adults. In order to determine whether hair
      analysis could discriminate between chronic use and acute administration of a
      drug in children like in adults, we analyzed hair from 18 children aged between 1
      day and 15 years in whom the administration of different drugs was known (single
      therapeutic administration or acute intoxication). A strand of hair was sampled
      within 1 to 45 days after treatment or intoxication. Analysis was conducted using
      LC/MS/MS. In the 10 youngest children, aged between 1 day and 29 months, the
      compounds administered in hospital or responsible for intoxication (lidocaine,
      ropivacaine, diazepam, midazolam, levetiracetam, morphine, ketamine, methadone,
      buprenorphine, THC, MDMA) were found in all segments of the hair independently of
      the time of sampling (1-45 days after ingestion). The concentrations detected
      were similar along the hair shaft, showing a radial diffusion and incorporation
      of the analytes in the hair of young children from the sebum. Concentrations
      could be very high when sampled shortly after administration (72 ng/mg for
      methadone, 75 ng/mg for MDMA after 3 days) and lower when sampling later (1.2
      ng/mg for MDMA after 45 days). In these cases, hair analysis allowed to highlight
      the compounds responsible for intoxication even when they had disappeared from
      the blood or urine but should not be used to discriminate long-term exposure to a
      drug. In the eight remaining children aged from 34 months to 15 years, the drugs
      used in hospital (lidocaine, diazepam, morphine) or responsible for intoxication
      (THC, codeine, buprenorphine) were not found in any analyzed segments sampled 1
      to 5 days after administration of the drugs, in agreement with the non
      incorporation of the drugs from the sebum into the hair. For those children aged
      over 34 months, hair analysis allows to determine the chronic administration of a
      drug, like in adults.

PMID- 29043490
TI  - HAQ score is an independent predictor of sustained remission in patients with
      rheumatoid arthritis: methodological issues.

PMID- 29043489
TI  - Comparative transcriptome analysis of Apis mellifera antennae of workers
      performing different tasks.
AB  - Honey bee is a social insect. Its colony is mainly coordinated by the chemical
      signals such as pheromones produced by queen or brood. Correspondingly, the
      worker bee developed numerous complicated olfactory sensilla in antennae for
      detection of these colony chemical signals and nectar/pollen signals in foraging.
      With the normal development of new emerged workers, young adults (nurse bee)
      worked in colony at the first 2-3 weeks and then followed by the foraging
      activity outside of the hive, which give rise to great change of the surrounding
      chemical signals. However, the olfactory adaption mechanism of worker bee in
      these processes of behavioral development is still unclear. In this study, we
      conducted a comprehensive and quantitative analysis of gene expression in Apis
      mellifera antenna of newly emerged workers, nurses and foragers using
      transcriptome analysis. Meanwhile, we constructed experimental colonies to
      collect age-matched samples, which were used to determine whether task is the
      principal determinant of differential expression. RNA sequencing and quantitative
      real-time polymerase chain reaction revealed that 6 and 14 genes were closely
      associated with nurse and forager behaviors, respectively. Furthermore, a broad
      dynamic range of chemosensory gene families and candidate odorant degrading
      enzymes were analyzed at different behavior statuses. We firstly reported genes
      associated with nursing/foraging behavior from antennae and the variations of
      expression of genes belonging to various olfactory gene families at different
      development stages. These results not only could contribute to elucidating the
      relationship between olfactory and behavior-related changes, but also provide a
      new perspective into the molecular mechanism underlying honey bee division of
      labor.

PMID- 29043491
TI  - The multifactorial origin of posterior reversible encephalopathy syndrome in
      cyclophosphamide-treated lupus patients.
AB  - The cyclophosphamide as a predisposing factor for Posterior Reversible
      Encephalopathy Syndrome (PRES) and therapeutic option for systemic lupus
      erythematosus (SLE) is still confusing. The first and only case of PRES, probably
      induced by cyclophosphamide, in Croatia followed by the findings of 36 SLE
      patients diagnosed with PRES after treatment with cyclophosphamide worldwide are
      described. An 18-year-old Caucasian female patient with a 1-year history of SLE
      was admitted to the hospital due to lupus nephritis and acute arthritis. After
      the second dose of cyclophosphamide was administered, according to the Euro-lupus
      protocol, the patient presented with a grand mal status epilepticus. The
      differential diagnosis of neurolupus, cerebrovascular insult, and infection were
      excluded. The MRI findings showed brain changes in corresponding to PRES. The
      treatment consisted of antihypertensives, antiepileptics, antiedema therapy,
      mechanical ventilation, and avoiding further cyclophosphamide use. A Naranjo
      Adverse Drug Reaction Probability Scale total score of five and a probable
      reaction related to drug therapy (cyclophosphamide, PRES) was confirmed. In this
      systematic review, along with cyclophosphamide use, the main predisposing factors
      involved in PRES occurrence in SLE patients were active SLE and renal
      involvement. Due to the high number of simultaneously involved predisposing
      factors (max. six) and their overlapping effect, it is still not possible to
      clearly establish the role of every factor on PRES onset. The use of
      cyclophosphamide, as a contributing factor for PRES onset, should be carefully
      assessed, based on clinicians' experience and knowledge, in the setting of active
      SLE.

PMID- 29043492
TI  - In reply to the letter to the Editor, "HAQ score is an independent predictor of
      sustained remission in patients with rheumatoid arthritis".

PMID- 29043493
TI  - Community-based intervention to promote physical activity in rheumatoid arthritis
      (CIPPA-RA): a study protocol for a pilot randomised control trial.
AB  - Rheumatoid arthritis (RA) is a chronic, inflammatory condition which may cause
      pain, stiffness and fatigue. People who have RA have reduced levels of physical
      activity due to these symptoms. Interventions targeting physical activity
      behaviour in this population have had limited efficacy. This paper describes a
      protocol for a pilot randomised controlled trial (RCT) of a theory-based
      intervention delivered in a community setting designed to promote physical
      activity in people who have RA. The aim of the pilot study is to assess the
      impact of the intervention on moderate-intensity physical activity in people with
      RA. The objectives are to obtain reliable estimates regarding recruitment rates;
      participant retention, protocol adherence and generate potential effect size
      estimates to inform sample size calculations for a main trial on physical
      activity participation. Semi-structured interviews will be conducted with a
      selected sample of participants to explore their experiences. Participants will
      be recruited from direct referrals from the rheumatology clinics in a public
      hospital. Participants meeting inclusion criteria will be randomised into a 6
      week physical activity intervention (four sessions delivered over a 6-week period
      by a trained physiotherapist) or a control group (physical activity information
      leaflet). Results of the pilot study will provide data to determine if a larger
      RCT is feasible. Qualitative data will inform intervention design and delivery.
      The findings will be disseminated to health professionals, in peer-reviewed
      journals and conference presentations.

PMID- 29043495
TI  - Endogenous control of fuelling in a migratory songbird.
AB  - The Northern wheatear (Oenanthe oenanthe) is a small long-distance migratory
      songbird that breeds throughout the Northern hemisphere and winters in sub
      Saharan Africa. The main components of its migratory behaviour, i.e. seasonal
      migratory restlessness and body mass changes, have been shown to be under
      endogenous control. However, it is still unknown whether the disposition to
      accumulate fuel reserves is an inherited trait. We cross-bred Northern wheatears
      from two populations known to accumulate different amounts of fuel in a common
      garden setup, and measured their maximum fuelling as the difference between the
      lightest and heaviest body mass recorded over each year for 4 years or longer. We
      used the largest value as a measure of maximum voluntary fuelling potential. F1
      generation "hybrids" showed intermediate values to those of the parent
      populations. It was previously shown that in the wheatear the amount of fuel
      accumulated is closely linked to the presence of large ecological barriers to
      cross. This study shows that this adaptation has been fixed at the genetic level,
      and that intermediate traits are transferred to the next generation, with
      possible implications on the viability of such individuals in nature.

PMID- 29043494
TI  - Influence of Proline Substitution on the Bioactivity of Mammalian-Derived
      Antimicrobial Peptide NK-2.
AB  - Multidrug-resistant bacteria are emerging as a global threat, making the search
      for alternative compounds urgent. Antimicrobial peptides (AMPs) became a
      promising hotspot due to their distinct action mechanism and possibility to be
      used as an alternative or complement to traditional antibiotics. However, gaining
      a better understanding about the relationship between antimicrobial peptides
      structure and its bioactivity is crucial for the development of next generation
      of antimicrobial agents. NK-2, derived from mammalian protein NK-lysin, has
      potent antitumor and bactericidal abilities. As proline was considered to be an
      effective alpha-helix breaker due to its restricted conformation, to better
      comprehend the effects of proline in the structure-activity relationship of NK-2,
      we constructed two NK-2 analogs. We examined the biological activities of NK-2
      and its proline substitution analogs and analyzed the resulting conformational
      changes. Our results showed that introducing proline into the primary sequence of
      NK-2 significantly decreased the antitumor, antibacterial, and cytotoxic effects,
      as well as DNA binding activity by changing the alpha-helix content. However,
      alpha-helical content was not the only determining factor, the position of
      proline inserted was also critical. This study will allow for clearer insight
      into the role of proline in structure and bioactivity of NK-2 and provide a
      foundation for future studies.

PMID- 29043496
TI  - Erlotinib Plus Bevacizumab Phase ll Study in Patients with Advanced Non-small
      Cell Lung Cancer (JO25567): Updated Safety Results.
AB  - INTRODUCTION: The phase II JO25567 study compared the efficacy and safety of
      erlotinib plus bevacizumab vs. erlotinib alone as first-line therapy for advanced
      epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung
      cancer (NSCLC). OBJECTIVE: Our objective is to provide updated analyses of safety
      and the assessment of manageability of specific adverse events. METHODS: Patients
      with stage IIIB/IV or recurrent, non-squamous, EGFR mutation-positive NSCLC were
      randomized to receive erlotinib plus bevacizumab or erlotinib. The primary
      endpoint was progression-free survival. Adverse event frequency rates,
      predictability and manageability, reasons for discontinuation, time to onset, and
      outcomes of specific adverse events were analyzed. RESULTS: The safety analysis
      population comprised 152 randomized patients (75 erlotinib plus bevacizumab; 77
      erlotinib) who received at least one dose of study drug between February 2011 and
      March 2012. There was no difference in overall incidence of serious adverse
      events between arms, but more grade 3 or higher adverse events were reported with
      erlotinib plus bevacizumab (90.7%) than with erlotinib (53.2%), primarily due to
      grade 3 hypertension. Hypertension was controllable with antihypertensive
      medications in most cases. Proteinuria and bleeding were also more frequently
      reported with erlotinib plus bevacizumab than with erlotinib but were manageable
      and did not lead to early discontinuations. CONCLUSIONS: The addition of
      bevacizumab to erlotinib prolonged progression-free survival in EGFR mutation
      positive NSCLC. Follow-up safety data were consistent with the known safety
      profiles of both erlotinib and bevacizumab in NSCLC; this combination appeared to
      be manageable, and treatment was well tolerated. JapicCTI-111390.

PMID- 29043497
TI  - Characterization of Actinidia virus 1, a new member of the family Closteroviridae
      encoding a thaumatin-like protein.
AB  - A new member of the family Closteroviridae was detected in Actinidia chinensis
      grown in Italy, using next generation sequencing of double-stranded RNA. The
      virus isolate, named Actinidia virus 1 (AcV-1) has a genome of 18,848 nts in
      length, a structure similar to the unclassified persimmon virus B (PeVB) and
      contains 12 open reading frames (ORFs) greater than 6 KDa, one carrying two
      papain-like leader proteases, a methyltransferase, a helicase and an RNA
      dependent RNA polymerase domain. Additional ORFs code for homologs of heat shock
      protein 70, heat shock protein 90 and a coat protein. Curiously, AcV-1 and PeVB
      genomes code for a thaumatin-like protein, a peculiarity unreported for other
      viruses. In phylogenetic analyses both viruses group in a distinct clade
      evolutionarily related to closteroviruses. The final taxonomic position of AcV-1
      within the family Closteroviridae is yet to be clarified.

PMID- 29043498
TI  - Sex-specific strategies of resource allocation in response to competition for
      light in a dioecious plant.
AB  - The differential plasticity hypothesis suggests that sexual dimorphism in
      dioecious plants could evolve in response to sex-specific resource requirements
      for reproduction (i.e., high carbon requirements for ovules and high nitrogen
      demands for pollen). When resources become limiting during growth, males and
      females should, therefore, adjust their allocation to resource-harvesting organs
      differently. To investigate the potential for plants to respond to resource
      limitation late in life and to test the differential plasticity hypothesis, we
      grew male and female individuals of the annual wind-pollinated plant Mercurialis
      annua in a common garden. Late in the growth season, we simulated a change in
      competition by decreasing plant density in half of the replicates. We measured
      both allocation to vegetative and reproductive traits and analyzed the relative
      allocation to reproduction vs. growth. Males and females differentially adjusted
      their resource allocation in response to varying plant densities, despite the
      fact that they were reproductively mature. Males maintained the same relative
      allocation of resource to reproductive vs. vegetative tissues at both densities.
      In contrast, females reduced vegetative growth proportionally less than seed
      production at the higher density. Our results highlight the dynamic nature of
      allocation decisions taken by plants, which respond quickly and in a sexually
      dimorphic way to changes in their competitive circumstances. The existence of
      resource 'currencies' limiting male and female functions differently have
      potentially led to the evolution of sex-specific strategies of resource
      acquisition and deployment, with females conserving resources for vegetative
      organs to ensure their future carbon-rich reproduction.

PMID- 29043499
TI  - Open-circuit respirometry: a historical review of portable gas analysis systems.
AB  - Scientists such as physiologists, engineers, and nutritionists have often sought
      to estimate human metabolic strain during daily activities and physical pursuits.
      The measurement of human metabolism can involve direct calorimetry as well as
      indirect calorimetry using both closed-circuit respirometry and open-circuit
      methods that can include diluted flow chambers and laboratory-based gas analysis
      systems. For field studies, methods involving questionnaires, pedometry,
      accelerometery, heart rate telemetry, and doubly labelled water exist, yet
      portable metabolic gas analysis remains the gold standard for most field studies
      on energy expenditure. This review focuses on research-based portable systems
      designed to estimate metabolic rate typically under steady-state conditions by
      critically examining each significant historical innovation. Key developments
      include Zuntz's 1906 innovative system, then a significant improvement to this
      purely mechanical system by the widely adopted Kofranyi-Michaelis device in the
      1940s. Later, a series of technical improvements: in electronics lead to Wolf's
      Integrating Motor Pneumotachograph in the 1950s; in polarographic O2 cells in
      1970-1980's allowed on-line oxygen uptake measures; in CO2 cells in 1990s allowed
      on-line respiratory exchange ratio determination; and in advanced
      sensors/computing power at the turn of the century led to the first truly breath
      by-breath portable systems. Very recent significant updates to the popular Cosmed
      and Cortex systems and the potential commercial release of the NASA-developed
      'PUMA' system show that technological developments in this niche area are still
      incrementally advancing.

PMID- 29043500
TI  - Optimal pacing and carbohydrate intake strategies for ultramarathons.
AB  - PURPOSE: The purpose of this research is to determine the pacing and nutrition
      strategies which minimize completion time and carbohydrate intake for athletes
      competing in ultramarathon races. METHODS: We present the formulation of a two
      phase optimization model. The first-phase mixed-integer nonlinear program (MINLP)
      determines the minimum completion time subject to the altitude, terrain, and
      distance of the race, as well as the mass and cardiovascular fitness of the
      athlete. The second-phase MINLP determines the minimum carbohydrate intake
      required for the athlete to achieve the completion time prescribed by the first
      phase subject to the flow of carbohydrates through the stomach, liver, and
      muscles. Consequently, the second-phase model provides the optimal pacing and
      nutrition strategies for a particular athlete for each kilometer of a particular
      race. RESULTS: We validate model results for a wide range of athlete parameters
      by comparing completion times to those reported for two case-study events. We
      also compare the kilometer-by-kilometer pacing and nutrition strategies
      prescribed by the model to those of a particular athlete. In all cases, the model
      results closely match those witnessed in the actual events. CONCLUSION: We have
      developed a baseline metabolic model that provides athletes prescriptive guidance
      regarding optimal pacing and carbohydrate intake strategies prior to competing in
      ultramarathon races. Given the highly variable topographical characteristics
      common to many ultramarathon courses and the potential inexperience of many
      athletes with such courses, our model provides valuable insight to competitors
      who might otherwise fail to complete the event due to exhaustion or carbohydrate
      depletion.

PMID- 29043501
TI  - Salmon Bias or Red Herring? : Comparing Adult Mortality Risks (Ages 30-90)
      between Natives and Internal Migrants: Stayers, Returnees and Movers in
      Rotterdam, the Netherlands, 1850-1940.
AB  - The purpose of this research is to empirically test the salmon bias hypothesis,
      which states that the "healthy migrant" effect-referring to a situation in which
      migrants enjoy lower mortality risks than natives-is caused by selective return
      migration of the weak, sick, and elderly. Using a unique longitudinal micro-level
      database-the Historical Sample of the Netherlands-we tracked the life courses of
      internal migrants after they had left the city of Rotterdam, which allowed us to
      compare mortality risks of stayers, returnees, and movers using survival analysis
      for the study group as a whole, and also for men and women separately. Although
      migrants who stayed in the receiving society had significantly higher mortality
      risks than natives, no significant difference was found for migrants who returned
      to their municipality of birth (returnees). By contrast, migrants who left for
      another destination (movers) had much lower mortality risks than natives. Natives
      who left Rotterdam also had significantly lower mortality risks than natives who
      stayed in Rotterdam. Female migrants, in particular, who stayed in the receiving
      urban society paid a long-term health price. In the case of Rotterdam, the salmon
      bias hypothesis can be rejected because the lower mortality effect among migrants
      was not caused by selective return-migration. The healthy migrant effect is real
      and due to a positive selection effect: Healthier people are more likely to
      migrate.

PMID- 29043502
TI  - An Integrated Approach Using Chaotic Map & Sample Value Difference Method for
      Electrocardiogram Steganography and OFDM Based Secured Patient Information
      Transmission.
AB  - This paper presents a patient's confidential data hiding scheme in
      electrocardiogram (ECG) signal and its subsequent wireless transmission.
      Patient's confidential data is embedded in ECG (called stego-ECG) using chaotic
      map and the sample value difference approach. The sample value difference
      approach effectually hides the patient's confidential data in ECG sample pairs at
      the predefined locations. The chaotic map generates these predefined locations
      through the use of selective control parameters. Subsequently, the wireless
      transmission of the stego-ECG is analyzed using the Orthogonal Frequency Division
      Multiplexing (OFDM) system in a Rayleigh fading scenario for telemedicine
      applications. Evaluation of proposed method on all 48 records of MIT-BIH
      arrhythmia ECG database demonstrates that the embedding does not alter the
      diagnostic features of cover ECG. The secret data imperceptibility in stego-ECG
      is evident through the statistical and clinical performance measures. Statistical
      measures comprise of Percentage Root-mean-square Difference (PRD), Peak Signal to
      Noise Ratio (PSNR), and Kulback-Leibler Divergence (KL-Div), etc. while clinical
      metrics includes wavelet Energy Based Diagnostic Distortion (WEDD) and Wavelet
      based Weighted PRD (WWPRD). The various channel Signal-to-Noise Ratio scenarios
      are simulated for wireless communication of stego-ECG in OFDM system. The
      proposed method over all the 48 records of MIT-BIH arrhythmia database resulted
      in average, PRD = 0.26, PSNR = 55.49, KL-Div = 3.34 * 10-6, WEDD = 0.02, and
      WWPRD = 0.10 with secret data size of 21Kb. Further, a comparative analysis of
      proposed method and recent existing works was also performed. The results
      clearly, demonstrated the superiority of proposed method.

PMID- 29043503
TI  - Pharmacoperones for Misfolded Gonadotropin Receptors.
AB  - The gonadotropin receptors (luteinising hormone receptor; LHR and follicle
      stimulating hormone receptor; FSHR) are G protein-coupled receptors (GPCRs) that
      play an important role in the endocrine control of reproduction. Thus genetic
      mutations that cause impaired function of these receptors have been implicated in
      a number of reproductive disorders. Disease-causing genetic mutations in GPCRs
      frequently result in intracellular retention and degradation of the nascent
      protein through misfolding and subsequent recognition by cellular quality control
      machinery. The discovery and development of novel compounds termed
      pharmacological chaperones (pharmacoperones) that can stabilise misfolded
      receptors and restore trafficking and plasma membrane expression are therefore of
      great interest clinically, and promising in vitro data describing the
      pharmacoperone rescue of a number of intracellularly retained mutant GPCRs has
      provided a platform for taking these compounds into in vivo trials.
      Thienopyrimidine small molecule allosteric gonadotropin receptor agonists (Org
      42599 and Org 41841) have been demonstrated to have pharmacoperone activity.
      These compounds can rescue cell surface expression and in many cases, hormone
      responsiveness, of a range of retained mutant gonadotropin receptors. Should
      gonadotropin receptor selectivity of these compounds be improved, they could
      offer therapeutic benefit to subsets of patients suffering from reproductive
      disorders attributed to defective gonadotropin receptor trafficking.

PMID- 29043505
TI  - Structural and Functional Analysis of Sodium Channels Viewed from an Evolutionary
      Perspective.
AB  - Voltage-gated sodium channels initiate and propagate action potentials in
      excitable cells. They respond to membrane depolarization through opening,
      followed by fast inactivation that terminates the sodium current. This ON-OFF
      behavior of voltage-gated sodium channels underlays the coding of information and
      its transmission from one location in the nervous system to another. In this
      review, we explore and compare structural and functional data from prokaryotic
      and eukaryotic channels to infer the effects of evolution on sodium channel
      structure and function.

PMID- 29043504
TI  - The Molecular Physiopathogenesis of Islet Amyloidosis.
AB  - Human islet amyloid polypeptide or amylin (hA) is a 37-amino acid peptide hormone
      produced and co-secreted with insulin by pancreatic beta-cells. Under
      physiological conditions, hA regulates a broad range of biological processes
      including insulin release and slowing of gastric emptying, thereby maintaining
      glucose homeostasis. However, under the pathological conditions associated with
      type 2 diabetes mellitus (T2DM), hA undergoes a conformational transition from
      soluble random coil monomers to alpha-helical oligomers and insoluble beta-sheet
      amyloid fibrils or amyloid plaques. There is a positive correlation between hA
      oligomerization/aggregation, hA toxicity, and diabetes progression. Because the
      homeostatic balance between hA synthesis, release, and uptake is lost in
      diabetics and hA aggregation is a hallmark of T2DM, this chapter focuses on the
      biophysical and cell biology studies investigating molecular mechanisms of hA
      uptake, trafficking, and degradation in pancreatic cells and its relevance to h's
      toxicity. We will also discuss the regulatory role of endocytosis and proteolytic
      pathways in clearance of toxic hA species. Finally, we will discuss potential
      pharmacological approaches for specific targeting of hA trafficking pathways and
      toxicity in islet beta-cells as potential new avenues toward treatments of T2DM
      patients.

PMID- 29043506
TI  - Fatigue failure of the cephalomedullary nail: revision options, outcomes and
      review of the literature.
AB  - Cephalomedullary nail (CMN) failure is a rare entity following hip fracture
      treatment. However, it poses significant challenges for revision surgery, both
      mechanically and biologically. Nail failure rates have been reported at < 2%;
      however, no published studies have reported revision surgery procedures and their
      respective outcomes. We present a regional experience, with outcomes, of the
      revision options. We identified 20 fatigued CMNs that underwent four different
      revision procedures. Mean age was 73 +/- 15.24 years, with a 3:1 female
      preponderance, and a median ASA grade of 3. Post-operative CMN radiographs
      demonstrated a significant number of fractures were fixed in varus, with
      reductions in neck-shaft angles post-operatively. A "poor" quality of reduction
      resulted in significantly earlier nail failure, compared to "adequate" and "good"
      (p = 0.027). Tip-Apex Distance (TAD) mean was 23.2 +/- 8.3 mm, and an adequate
      TAD with three-point fixation was seen in only 35% of cases. Mean time to failure
      was 401.0 +/- 237.2 days, with mean age at failure of 74.0 +/- 14.8 years.
      Options after failure included revision CMN nail, proximal femoral locking plate
      (PFLP), long-stem or restoration arthroplasty, or femoral endoprosthesis. Barthel
      Functional Index scores showed no significant difference at 3 and 12 months post
      operatively, nor any difference between treatment groups. Mean 12-month mortality
      was 30%, akin to a primary hip fracture mortality risk according to NICE
      guidelines. Mortality rates were lowest in revision nails. Subsequent revision
      rates were higher in the PFLP group. There is no reported evidence on the best
      surgical technique for managing the failed CMN, with no clear functional benefit
      in the options above. Good surgical technique at the time of primary CMN surgery
      is critical in minimising fatigue failure. After revision, overall mortality
      rates were equivalent to reported primary hip fracture mortality rates. Further
      multicentre evaluations are required to assess which technique convey the best
      functional outcomes without compromising 12-month mortality rates.

PMID- 29043507
TI  - Extraction of mandibular premolars and molars: comparison between local
      infiltration via pressure syringe and inferior alveolar nerve block anesthesia.
AB  - OBJECTIVES: The purpose of this study was to evaluate the anesthetic efficiency
      of local infiltration anesthesia administered with a pressure syringe (P-INF) via
      a special technique versus direct block anesthesia of the inferior alveolar nerve
      (IANB) for tooth extraction in the posterior mandible. MATERIALS AND METHODS: In
      a prospective randomized study, 101 teeth in 101 patients were extracted in the
      posterior mandible under local anesthesia whereby two different administration
      techniques were used (P-INF n = 48; IANB n = 53). Primary objectives were
      comparisons of anesthetic success rate (yes/no) and efficacy (full/sufficient vs.
      insufficient). Secondary objectives were patients' pain perception during
      treatment, pain of injection (numerical rating scale), need for second injections
      (always IANB), time until onset of anesthetic action (min), and duration of local
      numbness (min). RESULTS: IANB was successful in all cases, whereas initial P-INF
      achieved 35% of success only. Furthermore, IANB reached significant higher values
      of anesthetic efficacy compared to P-INF (P < 0.001). Concerning pain of
      injection, patients rated IANB to be more painful (P = 0.039). Second injections
      were significantly more often necessary for P-INF (P = 0.006) whereas duration
      until onset of action as well as the duration of local numbness were found to be
      equal. CONCLUSIONS: For anesthetic efficacy as well as anesthetic success, block
      anesthesia of the inferior alveolar nerve (IANB) turned out to be more proficient
      to local infiltration via special delivering system with a special technique.
      CLINICAL RELEVANCE: Infiltration, even when performed with 4% articaine and a
      pressure syringe system, is not a suitable method of anesthesia in the posterior
      mandible.

PMID- 29043509
TI  - Solid-State Heating Synthesis of Poly (3,4-Ethylenedioxythiophene)/Gold/Graphene
      Composite and Its Application for Amperometric Determination of Nitrite and
      Iodate.
AB  - A ternary composite of poly (3,4-ethylenedioxythiophene)/gold/graphene
      (PEDOT/Au/GO) for promising electrochemical sensor was synthesized by solid-state
      heating method. The interaction between the PEDOT, Au, and GO explored for
      detection of nitrite and iodate. It was found that the PEDOT/Au/GO composite had
      shale-like morphology with a uniform distribution of gold nanoparticles.
      Electrochemical experiments showed that the PEDOT/Au/GO composite modified
      electrode exhibited good electrocatalytic activity toward determination of
      iodate. The amperometric experiments at the PEDOT/Au/GO/GCE revealed that a good
      linear relationship existed between peak current and the concentration in the
      range of 100-1000 MUM with the detection of 0.53 and 0.62 MUM (S/N = 3) for
      nitrite and iodate, respectively. Moreover, the current response of
      PEDOT/Au/GO/GCE for nitrite and iodate at 10 MUM was up to 9.59 and 11.47 MUA,
      respectively. Mechanisms of the direct electron transfer between ion(nitrite or
      iodate)and the PEDOT/Au/GO composite.

PMID- 29043508
TI  - The role of PI3Kalpha isoform in cardioprotection.
AB  - Ischemic preconditioning (IPC) limits myocardial infarct size through the
      activation of the PI3K-Akt signal cascade; however, little is known about the
      roles of individual PI3K isoforms in cardioprotection. We aimed, therefore, to
      elucidate the role of the PI3Kalpha isoform in cardioprotection Pharmacological
      PI3Kalpha inhibition was assessed in isolated-perfused mouse hearts subjected to
      ischemia/reperfusion injury (IRI), either during the IPC procedure or at
      reperfusion. PI3Kalpha inhibition abrogated the IPC-induced protective effect at
      reperfusion, but not when given only during the IPC protocol. These results were
      confirmed in an in vivo model. Moreover, pharmacological PI3Kalpha activation by
      insulin at reperfusion was sufficient to confer cardioprotection against IRI. In
      addition, PI3Kalpha was shown to be expressed and activated in mouse
      cardiomyocytes, mouse cardiac endothelial cells, as well as in mouse and human
      heart tissue. Furthermore, PI3Kalpha was shown to mediate its effect though the
      inhibition of mitochondrial permeability transition pore opening. In conclusion,
      PI3Kalpha activity is required during the early reperfusion phase to reduce
      myocardial infarct size. This suggests that strategies specifically enhancing the
      alpha isoform of PI3K at reperfusion promote tissue salvage and as such, and
      could provide a direct target for clinical treatment of IRI.

PMID- 29043511
TI  - Implication of decreased serum complement 3 in patients with diabetic
      nephropathy.
AB  - AIMS: The serum complement 3 (C3) level was reduced in many patients with type 2
      diabetes mellitus (T2DM) and diabetic nephropathy (DN). However, the clinical
      implications of such change are still less understood. This study was aimed to
      explore the association between C3 level and the baseline clinicopathological
      characteristics and the prognosis of T2DM patients with DN. METHODS: A total of
      171 T2DM patients with biopsy-proven DN who received follow-up for at least 1
      year were recruited. The patients were divided into two groups based on the C3
      level: decreased C3 group: < 90 mg/dl (n = 75) and normal C3 group: >= 90 mg/dl
      (n = 96). Renal outcomes were defined by progression to end-stage renal disease
      (ESRD) or doubling of serum creatinine (D-SCr) level. The influence of serum C3
      level on renal outcomes was estimated using Cox regression. RESULTS: The patients
      with decreased C3 level had more severe renal insufficiency and glomerular
      lesions than those in the normal C3 group. During a follow-up period (12-78
      months), 51 patients with decreased C3 levels (68.0%) and 36 individuals with
      normal C3 levels (37.5%) reached the endpoint. The univariate Cox regression
      indicated that patients in the decreased C3 group had a higher rate of the renal
      outcomes than patients in the normal C3 group (HR 1.897, 95% CI 1.235-2.913, p =
      0.003). But the multivariate COX analysis indicated that the C3 level was not an
      independent risk factor for progression to ESRD and/or D-SCr (HR 1.389, 95% CI
      0.847-2.278, p = 0.193) when adjusting for important clinical variables and
      pathological findings. CONCLUSIONS: Decreased serum C3 level was significantly
      associated with more severe renal insufficiency, higher glomerular grading and
      poor renal outcomes, though it failed to be an independent risk factor in T2DM
      patients with DN.

PMID- 29043512
TI  - Comparisons of Perceived Training Doses in Champion Collegiate-Level Male and
      Female Cross-country Runners and Coaches over the Course of a Competitive Season.
AB  - BACKGROUND: Session rating of perceived exertion (sRPE) is a practical tool for
      coaches to assess internal training load of their athletes. In a sport like cross
      country running, that is individual in nature, but has a team training and
      competition component, information about the association between external and
      internal load is lacking. Furthermore, there is a need for studies that examine
      perception of training doses across multiple training cycles including the
      competitive season as well as between male and female athletes. METHODS: Session
      RPE, duration, and training load (TLRPE = sRPE * duration) of 25 highly trained
      male and female cross-country runners and their coaches were recorded for every
      training session (110 days) throughout a collegiate cross-country season.
      Intensity (sRPE), duration, and TLRPE were compared between coaches and runners
      by gender separately. Training sessions were also analyzed by those intended by
      the coaches to be easy, moderate, and hard as well as by training period.
      RESULTS: Data from 3024 training sessions were collected, 62% of which were
      considered "easy," 18% "moderate," and 20% "hard." Men and women rated coach
      intended easy sessions significantly harder during each month of the season
      (effect size (ES) > 2.9, p < 0.0001). Men rated moderate intensity sessions
      significantly higher than coaches (ES >= 1.0, p <= 0.002), whereas females rated
      hard intensity sessions significantly lower than coaches (ES > 0.5, p < 0.008).
      There was no difference between males and coach's hard sessions (ES < 0.07, p >
      0.05) or females and coach's moderate sessions (ES < 0.18, p > 0.05). Training
      intensity and TLRPE tended to increase throughout the season (p > 0.05), with a
      significant increase in moderate and hard intensity sessions in the last training
      period (p < 0.001). CONCLUSIONS: The results indicate the male and female cross
      country runners tend to regress to moderate intensity training throughout the
      cross-country season. Given the success of the athletes in this study, these
      results show how a simple system for monitoring training such as the sRPE method
      may improve control of training variables and provide a useful tool for coaches
      to evaluate training load placed on athletes in a simple, responsive way.

PMID- 29043510
TI  - Taurine as a water structure breaker and protein stabilizer.
AB  - The enhancing effect on the water structure has been confirmed for most of the
      osmolytes exhibiting both stabilizing and destabilizing properties in regard to
      proteins. The presented work concerns osmolytes, which should be classified as
      "structure breaking" solutes: taurine and N,N,N-trimethyltaurine (TMT). Here, we
      combine FTIR spectroscopy, DSC calorimetry and DFT calculations to gain an
      insight into the interactions between osmolytes and two proteins: lysozyme and
      ubiquitin. Despite high structural similarity, both osmolytes exert different
      influence on protein stability: taurine is a stabilizer, TMT is a denaturant. We
      show also that taurine amino group interacts directly with the side chains of
      proteins, whereas TMT does not interact with proteins at all. Although two
      solutes weaken on average the structure of the surrounding water, their hydration
      spheres are different. Taurine is surrounded by two populations of water
      molecules: bonded with weak H-bonds around sulfonate group, and strongly bonded
      around amino group. The strong hydrogen-bonded network of water molecules around
      the amino group of taurine further improves properties of enhanced protein
      hydration sphere and stabilizes the native protein form. Direct interactions of
      this group with surface side chains provide a proper orientation of taurine and
      prevents the [Formula: see text] group from negative influence. The weakened
      [Formula: see text] hydration sphere of TMT breaks up the hydrogen-bonded network
      of water around the protein and destabilizes it. However, TMT at low
      concentration stabilize both proteins to a small extent. This effect can be
      attributed to an actual osmophobic effect which is overcome if the concentration
      increases.

PMID- 29043513
TI  - Highly Enhanced H2 Sensing Performance of Few-Layer MoS2/SiO2/Si Heterojunctions
      by Surface Decoration of Pd Nanoparticles.
AB  - A novel few-layer MoS2/SiO2/Si heterojunction is fabricated via DC magnetron
      sputtering technique, and Pd nanoparticles are further synthesized on the device
      surface. The results demonstrate that the fabricated sensor exhibits highly
      enhanced responses to H2 at room temperature due to the decoration of Pd
      nanoparticles. For example, the Pd-decorated MoS2/SiO2/Si heterojunction shows an
      excellent response of 9.2 * 103% to H2, which is much higher than the values for
      the Pd/SiO2/Si and MoS2/SiO2/Si heterojunctions. In addition, the H2 sensing
      properties of the fabricated heterojunction are dependent largely on the
      thickness of the Pd-nanoparticle layer and there is an optimized Pd thickness for
      the device to achieve the best sensing characteristics. Based on the
      microstructure characterization and electrical measurements, the sensing
      mechanisms of the Pd-decorated MoS2/SiO2/Si heterojunction are proposed. These
      results indicate that the Pd decoration of few-layer MoS2/SiO2/Si heterojunctions
      presents an effective strategy for the scalable fabrication of high-performance
      H2 sensors.

PMID- 29043515
TI  - The 2018 International Workshop on Statistical Genetic Methods for Human Complex
      Traits : (Formerly the 'Methodology of Twin and Family Studies Introductory
      Workshop'): March 5th-March 9th, 2018.

PMID- 29043514
TI  - Efficacy of a triplet and doublet-based chemotherapy as first-line therapy in
      patients with HER2-negative metastatic gastric cancer: a retrospective analysis
      from the clinical practice.
AB  - : The best choice of chemotherapy regimen for patients with metastatic gastric
      cancer is still debated. Although several studies support a superior efficacy of
      a triplet chemotherapy regimen over a doublet-based regimen, the magnitude of
      this benefit appears small and accompanied by an increased toxicity. Based on
      this background, we evaluated the outcome of patients with HER2-negative
      metastatic gastric cancer (mGC) who received in the clinical practice a triplet
      or doublet regimen as first-line therapy. A total of 165 patients (pts) with HER2
      negative mGC treated outside of clinical trials at our department with FOLFOX-4
      or ECX from 2012 and 2015 were included in our retrospective analysis: FOLFOX-4:
      86 pts; ECX: 79 pts. Median progression-free survival (PFS) was 5.1 months for
      FOLFOX-4 and 5.6 months for ECX regimen, respectively. Median overall survival
      (OS) was 10.3 months for FOLFOX-4 and 10.9 months for ECX regimens. TOXICITY:
      grade 3-4 vomiting (12.6%), neutropenia (31.6%), mucositis (11.3%) and fatigue
      (22.7%) occurred more frequently in ECX regimen, while grade 3-4 peripheral
      neuropathy was more common with FOLFOX-4 (19.7%). Both evaluated regimens are
      active and safe in the palliation of HER2-negative mGC in the first-line setting:
      Three-drug chemotherapy regimen appear more active but offer only a slight
      improvement in OS with an increased G3-G4 toxicity. Our data suggest that a
      doublet therapy should be preferred in the clinical practice, preferentially
      reserving a three-drug combination to pts with bulky disease and/or to pts with
      initially unresectable locally advanced disease.

PMID- 29043517
TI  - Awards Presented at the 47th Annual Meeting of the BEHAVIOR GENETICS ASSOCIATION
      : Thursday, July 1st, Oslo, Norway.

PMID- 29043516
TI  - Minutes of the Annual Business Meeting of the Members of the Behavior Genetics
      Association : Wednesday, June 30, 2017, 12:00-1:30 pm Oslo, Norway.

PMID- 29043518
TI  - Referees for Volume 47.

PMID- 29043519
TI  - Announcement of the Fulker Award for a Paper Published in Behavior Genetics,
      Volume 46, 2016.

PMID- 29043520
TI  - An Extended Twin-Pedigree Study of Neuroticism in the Netherlands Twin Register.
AB  - For the participants in the Netherlands Twin Register (NTR) we constructed the
      extended pedigrees which specify all relations among nuclear and larger twin
      families in the register. A total of 253,015 subjects from 58,645 families were
      linked to each other, to the degree that we had information on the relations
      among participants. We describe the algorithm that was applied to construct the
      pedigrees. For > 30,000 adolescent and adult NTR participants data were available
      on harmonized neuroticism scores. We analyzed these data in the Mendel software
      package (Lange et al., Bioinformatics 29(12):1568-1570, 2013) to estimate the
      contributions of additive and non-additive genetic factors. In contrast to much
      of the earlier work based on twin data rather than on extended pedigrees, we
      could also estimate the contribution of shared household effects in the presence
      of non-additive genetic factors. The estimated broad-sense heritability of
      neuroticism was 47%, with almost equal contributions of additive and non-additive
      (dominance) genetic factors. A shared household effect explained 13% and unique
      environmental factors explained the remaining 40% of the variance in neuroticism.

PMID- 29043521
TI  - Initiation of antihypertensive monotherapy and incident fractures among Medicare
      beneficiaries.
AB  - BACKGROUND: Research suggests antihypertensive medications are associated with
      fractures in older adults, however results are inconsistent and few have examined
      how the association varies over time. We sought to examine the association
      between antihypertensive class and incident non-vertebral fractures among older
      adults initiating monotherapy according to time since initiation. METHODS: We
      used a new-user cohort design to identify Medicare beneficiaries (>= 65 years of
      age) initiating antihypertensive monotherapy during 2008-2011 using a 20% random
      sample of Fee-For-Service Medicare beneficiaries enrolled in parts A (inpatient
      services), B (outpatient services), and D (prescription medication) coverage.
      Starting the day after the initial antihypertensive prescription, we followed
      beneficiaries for incident non-vertebral fractures. We used multinomial logistic
      regression models to estimate propensity scores for initiating each
      antihypertensive drug class. Using these propensity scores, we weighted
      beneficiaries to achieve the same baseline covariate distribution as
      beneficiaries initiating with angiotensin-converting enzyme inhibitors. Lastly,
      we used weighted Cox proportional hazard models to estimate hazard ratios (HRs)
      of having an incident fractures according to antihypertensive class and time
      since initiation. RESULTS: During 2008-2011, 122,629 Medicare beneficiaries
      initiated antihypertensive monotherapy (mean age 75, 61% women, 86% White).
      Fracture rates varied according to days since initiation and antihypertensive
      class. Beneficiaries initiating with thiazides had the highest fracture rate in
      the first 14 days following initiation (438 per 10,000 person-years, 95%
      confidence interval (CI): 294-628; HR: 1.40, 0.78-2.52). However, beneficiaries
      initiating with calcium channel blockers had the highest fracture rate during the
      15-365 days after initiation (435 per 10,000 person-years, 95% CI: 404-468; HR:
      1.11, 1.00-1.24). Beneficiaries initiating with angiotensin-receptor blockers had
      the lowest fracture rates during the initial 14 days (333 per 10,000 person
      years, 190-546, HR: 0.92, 0.49-1.75) and during 15-365 days after initiation (321
      per 10,000 person-years, 287-358, HR: 0.96, 0.84-1.09). CONCLUSION: The
      association between antihypertensives and fractures varied according to class and
      time since initiation. Results suggest that when deciding upon antihypertensive
      therapy, clinicians may want to consider possible fracture risks when choosing
      between antihypertensive drug classes.

PMID- 29043522
TI  - Cryovial monolayer vitrification for ovarian tissue cryopreservation.
AB  - The cryopreservation of ovarian tissue has been proved to be effective for
      fertility preservation. To find a better cryopreservation method, we tested the
      efficacy of cryovial monolayer vitrification method in comparison with that of
      needle immersed vitrification (NIV). Ovaries from 10 female kunming mice aged 6-8
      weeks were cut into pieces and allocated into group A (cryovial monolayer
      vitrification method), group B (NIV method) and group C (fresh control). In group
      A, pieces of ovarian tissue were layered around the inner wall of cryovial as a
      monolayer; and in group B, pieces of ovarian tissue were pierced with a needle.
      Other than the difference in the carrier for ovarian tissue, the cryoprotectants
      and the protocols in group A and B were the same. The viability and in vitro
      growth potential of the follicles after warming in groups A and B were evaluated
      respectively and compared with those of fresh control. The results showed that
      the viabilities of the follicles were not statistically different among three
      groups. The average diameter of follicles did not show statistically significant
      difference among three groups before culture and between group A and group B
      after culture (p > 0.05), but demonstrated statistically significant difference
      between group A and group C (p < 0.01), group B and group C (p < 0.01),
      respectively. In the procedure of loading ovarian tissue onto carriers, group A
      took less time compared with group B. In addition, the small pieces and debris
      which were harder or impossible to be pierced with needle in group B could be
      easily layered onto the inner wall of the cryovial in group A. Hence the
      follicles existed within the small pieces and debris of the ovarian tissue could
      also be cryopreserved. It is concluded that, in cryopreserving both viability and
      growth potential of follicles, the cryovial monolayer vitrification method is
      comparable with NIV method but with higher efficiency.

PMID- 29043523
TI  - Analysis of potential factors affecting allografts contamination at retrieval.
AB  - The microbiological contamination of retrieved tissues has become a very
      important topic and it is a critical aspect in the safety of allografts,
      especially from multi-tissue donors whose tissues are frequently contaminated as
      a consequence of retrieval. We analysed a total of 10,107 tissues, 8178
      musculoskeletal and 1929 cardiovascular tissues, retrieved from 978 multi-tissue
      donors. Of these, 159 heart-beating donors (HBD) were also organ donors, while
      the remaining 819 non-heart-beating donors (NHBD) were tissue donors only. A
      multivariate logistic model was used to determine the factors affecting
      contamination risk during retrieval. In the model, the dependent variable was the
      presence/absence of contamination while the covariates included were: gender,
      type of donor, age of donor, cause of death, previous skin donation, cadaver
      time, number of people attending the retrieval, number of tissues retrieved.
      Moreover, a second log-linear model was used to determine the number of strains
      isolated per tissue. Tissue contamination was statistically correlated with
      gender, type of donor, cadaver time, number of people attending the retrieval and
      season. In conclusion, to minimize the risk of bacterial contamination, aseptic
      techniques should be used at retrieval, with the number of retrieval team members
      kept to a minimum. In addition, cadaver time should be as short as possible and
      the donor should be refrigerated within a few hours after death.

PMID- 29043524
TI  - Improving the success rate of human corneal endothelial cell cultures from single
      donor corneas with stabilization medium.
AB  - Main objective of this study was to improve the success rate of human corneal
      endothelial cell (hCEC) cultures from single donor corneas. We could show that
      the use of stabilization medium prior to cell isolation may have a positive
      effect on the success rate of hCEC cultures from single research-grade donor
      corneas by allowing growth of otherwise possibly not successful cultures and by
      improving their proliferative rate. hCEC were obtained from corneo-scleral rims
      of 7 discarded human research-grade cornea pairs. The Descemet membrane
      endothelium (DM-EC) sheets of each pair were assigned to 2 experimental
      conditions: (1) immediate cell isolation after peeling, and (2) storage of the DM
      EC sheet in a growth factor-depleted culture medium (i.e. stabilization medium)
      for up to 6 days prior to cell isolation. hCEC isolated by enzymatic digestion
      were then induced to proliferate on pre-coated culture plates. The success rate
      of primary cultures established from single donor corneas were higher for DM-EC
      sheets kept in stabilization medium before cell isolation. All cultures (7/7)
      initiated from stabilized DM-EC sheets were able to proliferate up to the third
      passage, while only 4 out of 7 cultures initiated from freshly peeled DM-EC
      sheets reached the third passage. In addition, for the 4 successful paired
      cultures we observed a faster growth rate if the DM-EC sheet was pre-stabilized
      prior to cell isolation (13.8 +/- 1.8 vs 18.5 +/- 1.5 days, P < 0.05). Expression
      of the phenotypical markers Na+/K+-ATPase and ZO-1 could be shown for the
      stabilized cultures that successfully proliferated up to the third passage.

PMID- 29043525
TI  - Long-term Follow-up and Post-relapse Outcome of Patients with Localized
      Retroperitoneal Sarcoma Treated in the Italian Sarcoma Group-Soft Tissue Sarcoma
      (ISG-STS) Protocol 0303.
AB  - BACKGROUND: This study was designed to assess patterns of recurrence and long
      term outcomes of patients undergoing surgery for localized retroperitoneal
      sarcoma (RPS) after neoadjuvant high dose long-infusion ifosfamide (HLI) and
      radiotherapy (RT). METHODS: Patients received three cycles of HLI (14 g/m2). RT
      was started in combination with II cycle up to a total dose of 50.4 Gy. Surgery
      was scheduled 4-6 weeks after the end of RT. The primary endpoint was relapse
      free survival (RFS) after surgery. Secondary endpoints were overall survival
      (OS), crude cumulative incidence of local recurrence (CCI-LR), and distant
      metastases (CCI-DM). For patients who relapsed, progression-free survival (PFS)
      and post-relapse OS were estimated. The trial was registered with
      ITASARC_*II_2004_003. RESULTS: Between 2003 and 2010, 83 patients were recruited.
      At a median follow-up of 91.7 months, 42 (56%) of 75 operated patients developed
      LR (n = 27) or DM (n = 10) or both LR and DM (n = 5) relapse. Seven-year RFS was
      46.6% [95% confidence interval (CI) 29.6-52.4]. Thirty-two patients died. Seven
      year OS rate was 63.2% (95% CI 42.7-66.0). The corresponding CCI of LR and DM
      were 37.4% [standard error (SE) 5.5%] and 20.0% (SE 12.6%), respectively. The
      only factor significantly associated with LR was FNCLCC grading, whereas
      histological subtype resulted associated with DM. At recurrence, 24 patients
      (57%) underwent surgery. Two-year post-relapse PFS and OS rates for patients
      developing LR or DM were 14.8, 41.0, 27.3, and 63.6%, respectively. CONCLUSIONS:
      LR after neoadjuvant CT-RT for RPS were predominantly infield. While almost one
      half of relapsed patients underwent further surgery, prognosis was poor.

PMID- 29043526
TI  - Chemoradiation Therapy for Unresected Extrahepatic Cholangiocarcinoma: A
      Propensity Score-Matched Analysis.
AB  - BACKGROUND: Unresected extrahepatic cholangiocarcinoma (uEHCC) remains a deadly
      disease. Guidelines for uEHCC recommend either chemotherapy alone (CT) or
      chemoradiotherapy (CRT). This study used the National Cancer Database (NCDB) to
      compare outcomes for patients treated with CT and those who underwent CRT.
      METHODS: Patients with initially diagnosed non-metastatic uEHCC from 2004 to 2014
      were identified. Using Chi square analysis, patients who underwent CT were
      compared with those who received CRT. Uni- and multivariate Cox regression
      analyses were used to compare characteristics related to survival. Propensity
      score matching and shared frailty analysis were undertaken to correct for
      baseline differences between the two groups. Additional analyses were performed
      to compare survival for the minority of patients who underwent surgery and
      advanced-stage patients. RESULTS: The study identified 2996 patients with uEHCC.
      Chemoradiation was associated with better survival (median survival [MS], 14.5
      months; hazard ratio [HR] 0.84; p < 0.001) than CT alone (MS, 12.6 months).
      Induction of CT before CRT was associated with a trend toward decreased risk of
      death compared with concurrent CRT (HR 0.81; p = 0.051). For the patients able to
      undergo surgery after initial treatment, MS was 24.5 months (HR 0.38; p < 0.001)
      versus 12.2 months for those who had no surgery. For these patients, CRT also was
      associated with better survival (MS, 31.2 months; HR 0.66; p = 0.001) than CT
      (MS, 22.1 months). Positive margins at surgery yielded survival equivalent to
      that with no surgery. CONCLUSION: Although CRT may be associated with slightly
      better survival in uEHCC than CT alone, the majority of the benefit was observed
      for patients able to undergo eventual surgery.

PMID- 29043527
TI  - Na4Mn9O18/Carbon Nanotube Composite as a High Electrochemical Performance
      Material for Aqueous Sodium-Ion Batteries.
AB  - The aqueous sodium-ion battery (ASIB) is one of the promising new energy storage
      systems owing to the abundant resources of sodium as well as efficiency and
      safety of electrolyte. Herein, we report an ASIB system with Na4Mn9O18/carbon
      nanotube (NMO/CNT) as cathode, metal Zn as anode and a novel Na+/Zn2+ mixed ion
      as electrolyte. The NMO/CNT with microspherical structure is prepared by a simple
      spray-drying method. The prepared battery delivers a high reversible specific
      capacity and stable cyclability. Furthermore, the battery displays a stable
      reversible discharge capacity of 53.2 mAh g-1 even at a high current rate of 4 C
      after 150 cycles. Our results confirm that the NMO/CNT composite is a promising
      electrode cathode material for ASIBs.

PMID- 29043528
TI  - Comparison of Shallow and Deep Learning Methods on Classifying the Regional
      Pattern of Diffuse Lung Disease.
AB  - This study aimed to compare shallow and deep learning of classifying the patterns
      of interstitial lung diseases (ILDs). Using high-resolution computed tomography
      images, two experienced radiologists marked 1200 regions of interest (ROIs), in
      which 600 ROIs were each acquired using a GE or Siemens scanner and each group of
      600 ROIs consisted of 100 ROIs for subregions that included normal and five
      regional pulmonary disease patterns (ground-glass opacity, consolidation,
      reticular opacity, emphysema, and honeycombing). We employed the convolution
      neural network (CNN) with six learnable layers that consisted of four convolution
      layers and two fully connected layers. The classification results were compared
      with the results classified by a shallow learning of a support vector machine
      (SVM). The CNN classifier showed significantly better performance for accuracy
      compared with that of the SVM classifier by 6-9%. As the convolution layer
      increases, the classification accuracy of the CNN showed better performance from
      81.27 to 95.12%. Especially in the cases showing pathological ambiguity such as
      between normal and emphysema cases or between honeycombing and reticular opacity
      cases, the increment of the convolution layer greatly drops the misclassification
      rate between each case. Conclusively, the CNN classifier showed significantly
      greater accuracy than the SVM classifier, and the results implied structural
      characteristics that are inherent to the specific ILD patterns.

PMID- 29043529
TI  - Development and validation of a risk assessment tool for gastric cancer in a
      general Japanese population.
AB  - BACKGROUND: There have been very few reports of risk score models for the
      development of gastric cancer. The aim of this study was to develop and validate
      a risk assessment tool for discerning future gastric cancer risk in Japanese.
      METHODS: A total of 2444 subjects aged 40 years or over were followed up for 14
      years from 1988 (derivation cohort), and 3204 subjects of the same age group were
      followed up for 5 years from 2002 (validation cohort). The weighting (risk score)
      of each risk factor for predicting future gastric cancer in the risk assessment
      tool was determined based on the coefficients of a Cox proportional hazards model
      in the derivation cohort. The goodness of fit of the established risk assessment
      tool was assessed using the c-statistic and the Hosmer-Lemeshow test in the
      validation cohort. RESULTS: During the follow-up, gastric cancer developed in 90
      subjects in the derivation cohort and 35 subjects in the validation cohort. In
      the derivation cohort, the risk prediction model for gastric cancer was
      established using significant risk factors: age, sex, the combination of
      Helicobacter pylori antibody and pepsinogen status, hemoglobin A1c level, and
      smoking status. The incidence of gastric cancer increased significantly as the
      sum of risk scores increased (P trend < 0.001). The risk assessment tool was
      validated internally and showed good discrimination (c-statistic = 0.76) and
      calibration (Hosmer-Lemeshow test P = 0.43) in the validation cohort.
      CONCLUSIONS: We developed a risk assessment tool for gastric cancer that provides
      a useful guide for stratifying an individual's risk of future gastric cancer.

PMID- 29043530
TI  - Cox2A/Cox2B subunit interaction in Polytomella sp. cytochrome c oxidase: role of
      the Cox2B subunit extension.
AB  - Subunit II of cytochrome c oxidase (Cox2) is usually encoded in the mitochondrial
      genome, synthesized in the organelle, inserted co-translationally into the inner
      mitochondrial membrane, and assembled into the respiratory complex. In
      chlorophycean algae however, the cox2 gene was split into the cox2a and cox2b
      genes, and in some algal species like Chlamydomonas reinhardtii and Polytomella
      sp. both fragmented genes migrated to the nucleus. The corresponding Cox2A and
      Cox2B subunits are imported into mitochondria forming a heterodimeric Cox2
      subunit. When comparing the sequences of chlorophycean Cox2A and Cox2B proteins
      with orthodox Cox2 subunits, a C-terminal extension in Cox2A and an N-terminal
      extension in Cox2B were identified. It was proposed that these extensions favor
      the Cox2A/Cox2B interaction. In vitro studies carried out in this work suggest
      that the removal of the Cox2B extension only partially affects binding of Cox2B
      to Cox2A. We conclude that this extension is dispensable, but when present it
      weakly reinforces the Cox2A/Cox2B interaction.

PMID- 29043531
TI  - Desmoplastic Small Round Cell Tumor Presenting as an Ocular Mass: Unusual
      Localization and Remarkable Surgical Approach.
AB  - Desmoplastic small round cell tumor (DSRCT) is a rare tumor that was first
      described by Gerald and Rosai in 1989 as a mesenchymal entity. This tumor has a
      unique translocation t (11:22) (p:13, q:12) resulting in EWS/WT1 gene fusion that
      is diagnostic for DSCRT. The overall prognosis for desmoplastic small round cell
      tumor remains extremely poor, with reported rates of death as high as 90%.
      Although the majority of patients undergo chemotherapy following surgery, the
      prognosis has been shown to be independent of whether the surgical process
      preceded or followed chemotherapy. In this review, we provide insights for the
      management of DSCRT that requires aggressive multimodality therapy.

PMID- 29043532
TI  - Changes observed in urine microbiology following replacement of long-term urinary
      catheters: need to modify UTI guidelines in the UK?
AB  - AIMS: Bacteria adherent to long-term urinary catheters (LTUC) may give misleading
      urine culture results. Guidelines in the USA recommend changing LTUC before urine
      collection to diagnose UTI and before commencing appropriate antimicrobial
      treatment. However, in the UK there is no such guidance. In this study, we
      evaluated differences in urine cultures before and after changing LTUC. METHODS:
      In a prospective study in a UK urology department, we made a quantitative and
      qualitative comparison between paired urines collected before and after catheter
      change in patients with LTUC. We measured culture growth on a four-point ordinal
      scale as nil, scanty (< 107 cfu/L), moderate (107-108 cfu/L) or heavy (> 108
      cfu/L) and recorded the range of bacterial species isolated. Statistical analysis
      was by Wilcoxon matched-pairs test. RESULTS: Sixty-six patients (55 males, 11
      females) took part in the study. Urines with no growth increased from 7/66 (11%)
      before change of catheter to 21/66(32%) after change of catheter. Cultures
      reported as heavy growth (> 108 cfu/L) reduced from 48/66 (73%) to 25/66 (38%)
      after catheter change (p < 0.001). Except for Pseudomonas spp., other organisms
      were isolated less frequently after catheter change. No Proteus spp. was isolated
      after catheter change. CONCLUSIONS: This study confirms that failure to change
      long-term catheters before collecting urine for culture may give misleading
      results. In the interest of accurate diagnosis and antimicrobial stewardship, UK
      guidelines should recommend changing long-term urinary catheters before
      collection of urine for culture.

PMID- 29043533
TI  - Corneal Cross-Linking Has No Effect on Matrix Metalloproteinase 9 and 13 Levels
      During Fungal Keratitis on the Early Stage.
AB  - The aim of our study was to investigate matrix metalloproteinases, MMP-9 and MMP
      13 levels, in the rabbit model of Fusarium and Candida keratitis treated by
      corneal cross-linking (PACK-CXL). Rabbit corneas were inoculated with fungal
      inoculum for keratitis. Each group divided into four subgroups, including un
      treated group, PACK-CXL group, voriconazole group and PACK-CXL plus voriconazole
      group. PACK-CXL was applied with 0.25% riboflavin in accelerated Dresden
      protocol, and 0.1% voriconazole drops were administered. All corneal buttons
      excised at tenth day after ophthalmological examination. Fungal cell counts and
      Scheiber scores were determined in all groups. Corneal tissue MMP mRNA levels
      were evaluated quantitative reverse transcriptase PCR. The difference in MMP-9
      and MMP-13 levels at all groups was not statistically significant (p > 0.05).
      PACK-CXL with 0.25% riboflavin either alone or combined with antifungal drops was
      unable to provide decline in inflammatory findings in both macroscopic and
      microscopic levels similar to medical antifungal treatment.

PMID- 29043534
TI  - Male-Produced Aggregation Pheromone of Coffee Bean Weevil, Araecerus
      fasciculatus.
AB  - The coffee bean weevil (CBW), Araecerus fasciculatus (De Geer, 1775), is a
      cosmopolitan stored-product pest, especially in tropical and subtropical areas.
      Previous reports showed evidence for aggregation behavior of CBW and this study
      aimed to identify and evaluate the aggregation pheromone of this pest. Whole-body
      solvent extractions were analyzed by coupled gas chromatography-mass spectrometry
      and comparison of male and female extracts showed a male-specific compound which
      was identified as squalene, 2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22
      tetracosahexaene. This compound was shown to attract male and female CBW in Y
      tube olfactometer and storage trap assays. The longevity of septum lures was also
      evaluated in a warehouse. Squalene could be useful in monitoring and controlling
      this pest.

PMID- 29043536
TI  - Refining Risk for Deep Vein Thrombosis in Hospitalized Patients.

PMID- 29043535
TI  - Towards multilevel mental stress assessment using SVM with ECOC: an EEG approach.
AB  - Mental stress has been identified as one of the major contributing factors that
      leads to various diseases such as heart attack, depression, and stroke. To avoid
      this, stress quantification is important for clinical intervention and disease
      prevention. This study aims to investigate the feasibility of exploiting
      electroencephalography (EEG) signals to discriminate between different stress
      levels. We propose a new assessment protocol whereby the stress level is
      represented by the complexity of mental arithmetic (MA) task for example, at
      three levels of difficulty, and the stressors are time pressure and negative
      feedback. Using 18-male subjects, the experimental results showed that there were
      significant differences in EEG response between the control and stress conditions
      at different levels of MA task with p values < 0.001. Furthermore, we found a
      significant reduction in alpha rhythm power from one stress level to another
      level, p values < 0.05. In comparison, results from self-reporting questionnaire
      NASA-TLX approach showed no significant differences between stress levels. In
      addition, we developed a discriminant analysis method based on multiclass support
      vector machine (SVM) with error-correcting output code (ECOC). Different stress
      levels were detected with an average classification accuracy of 94.79%. The
      lateral index (LI) results further showed dominant right prefrontal cortex (PFC)
      to mental stress (reduced alpha rhythm). The study demonstrated the feasibility
      of using EEG in classifying multilevel mental stress and reported alpha rhythm
      power at right prefrontal cortex as a suitable index.

PMID- 29043537
TI  - Missed Doses of Venous Thromboembolism (VTE) Prophylaxis at Community Hospitals:
      Cause for Alarm.

PMID- 29043538
TI  - Venous thromboembolism prophylaxis in medically ill patients: a mixed treatment
      comparison meta-analysis.
AB  - The American College of Chest Physicians guidelines recommend unfractionated
      heparin (UFH), low molecular weight heparins (LMWHs) or fondaparinux for
      prevention of venous thromboembolism (VTE), including deep vein thrombosis (DVT)
      and pulmonary embolism (PE), in medically-ill patients. Direct oral
      anticoagulants (DOACs) have been evaluated relative to enoxaparin for VTE
      prophylaxis though head-to-head comparisons of these agents are lacking.
      Therefore, we conducted a mixed treatment comparisons meta-analysis to evaluate
      the safety and efficacy of established treatments and DOACs for VTE prophylaxis
      in medically-ill patients. A comprehensive literature search was conducted to
      identify randomized trials evaluating UFH, LMWHs or DOACS for the prevention of
      VTE in medically ill patients. Articles were retrieved and cross-referenced for
      additional trials, evaluated and entered into ADDIS (version 1.16.6) to generate
      direct and indirect treatment comparisons for VTE, DVT, PE, death from any cause,
      and bleeding. Ten articles were included and eight anticoagulants were evaluated
      in a treatment network representing data on 28,382 patients. We found each
      treatment had similar efficacy in preventing VTE, DVT, PE, death from any cause
      and each had similar risk of minor and major bleeding. Overall, placebo was
      associated with more VTE and DVT events compared to LMWHs and DOACs. We found
      that UFH, LMWHs and DOACs are comparable in preventing VTE, DVT, PE, and death
      from any cause and in association with minor and major bleeding. Anticoagulant
      selection for VTE prophylaxis in medically-ill patients should be individualized
      by patient characteristics, risks and preferences along with specific
      pharmacokinetic and pharmacodynamic considerations.

PMID- 29043539
TI  - Introduction: light harvesting for photosynthesis.

PMID- 29043540
TI  - Between quality of life and hope. Attitudes and beliefs of Muslim women toward
      withholding and withdrawing life-sustaining treatments.
AB  - The technological advances in medicine, including prolongation of life, have
      constituted several dilemmas at the end of life. In the context of the Belgian
      debates on end-of-life care, the views of Muslim women remain understudied. The
      aim of this article is fourfold. First, we seek to describe the beliefs and
      attitudes of middle-aged and elderly Moroccan Muslim women toward withholding and
      withdrawing life-sustaining treatments. Second, we aim to identify whether
      differences are observable among middle-aged and elderly women's attitudes toward
      withholding and withdrawing life-sustaining treatments. Third, we aim to explore
      the role of religion in their attitudes. Fourth, we seek to document how our
      results are related to normative Islamic literature. Qualitative empirical
      research was conducted with a sample of middle-aged and elderly Moroccan Muslim
      women (n = 30) living in Antwerp (Belgium) and with experts in the field (n =
      15). We found an unconditional belief in God's sovereign power over the domain of
      life and death (cf. determined lifespan by God) and in God's almightiness (cf.
      belief in a miracle). However, we also found a tolerant attitude, mainly among
      our middle-aged participants, toward withholding and withdrawing (treatment)
      based on theological, eschatological, financial and quality of life arguments.
      Our study reveals that religious beliefs and worldviews have a great impact on
      the ethical attitudes toward end-of-life issues. We found divergent positions
      toward withholding and withdrawing life-sustaining treatments, reflecting the
      lines of reasoning found in normative Islamic literature. In our interviews,
      theological and eschatological notions emerged as well as financial and quality
      of life arguments.

PMID- 29043541
TI  - An Unusual Progression of Signet-Ring Cell Carcinoma of the Appendix in a
      Caucasian Woman.

PMID- 29043542
TI  - Undergraduate basic surgical skills education: impact on attitudes to a career in
      surgery and surgical skills acquisition.
AB  - INTRODUCTION: Basic surgical skills modules in medical education are effective in
      teaching skills and increasing confidence among students approaching surgery.
      However, these modules are not delivered universally and their effect on the
      professional development of graduates has not been established. We aimed to
      assess the impact of a 10-week basic surgical skills module on attitudes and
      technical skills of first year medical students compared to interns. METHODS:
      Eighteen students participated and were assessed using a 4-part questionnaire.
      Technical skills were assessed by observing students perform a basic interrupted
      suture, using the objective structured assessment of technical skills (OSATS)
      tool. Fourteen interns were recruited. RESULTS: Students were more confident in
      surgical scrubbing (mean score 4.0 vs. 2.86, p = 0.001), and performing a basic
      suture (4.05 vs. 1.93, p = 0.000), more enthusiastic about assisting with an
      operation (4.5 vs. 3.0, p = 0.001) and more likely to consider a career in
      surgery (4.16 vs. 2.28, p = 0.000). Technical skills were greater in the student
      group (mean score 30.8 vs. 19.6, p = 0.001). Five interns had taken part in
      surgical skills modules as undergraduates. Their technical skills were
      significantly higher compared to interns who had not (n = 9) (28.8 vs. 14.5, p =
      0.006), and they were more likely to consider a career in surgery (3.6 vs. 1.5, p
      = 0.036). CONCLUSION: The introduction of surgical skills teaching to the
      undergraduate medical curriculum has a positive impact on students' attitudes
      towards surgery and accelerates basic technical skills development. Consideration
      should be given to development of a standardised undergraduate core curriculum in
      basic surgical skills teaching.

PMID- 29043543
TI  - Surgical management of splenic marginal zone lymphoma.
AB  - OBJECTIVES: Splenic marginal zone lymphoma (SMZL) is a rare indolent B-cell
      lymphoma with variable prognosis. As a result, there is sparse knowledge on the
      role of splenectomy and best management approaches. We aim to explore management
      strategies and outcomes amongst the cohort of SMZL patients at our centre.
      METHOD: A retrospective review of all splenectomies performed at a tertiary
      referral unit over a 23-year period was assessed. Immunohistochemical and
      pathological results of splenic samples, bone marrow biopsies, and peripheral
      blood were compiled. Operative management, surgical, and survival outcomes were
      assessed. Prognostic stratifications were applied and survival rates were
      calculated. RESULTS: Eight cases of SMZL from a database of 693 splenectomies
      were identified. All patients had intermediate/high-risk disease. All patients
      underwent splenectomy with one patient receiving preoperative rituximab. All
      patients had progression-free survival and resolution of disease. CONCLUSION:
      Based on the data obtained, current practice requires defined guidelines and
      centralised care.

PMID- 29043544
TI  - ICP Versus Laser Doppler Cerebrovascular Reactivity Indices to Assess Brain
      Autoregulatory Capacity.
AB  - BACKGROUND: To explore the relationship between various autoregulatory indices in
      order to determine which approximate small vessel/microvascular (MV)
      autoregulatory capacity most accurately. METHODS: Utilizing a retrospective
      cohort of traumatic brain injury patients (N = 41) with: transcranial Doppler
      (TCD), intracranial pressure (ICP) and cortical laser Doppler flowmetry (LDF), we
      calculated various continuous indices of autoregulation and cerebrovascular
      responsiveness: A. ICP derived [pressure reactivity index (PRx)-correlation
      between ICP and mean arterial pressure (MAP), PAx-correlation between pulse
      amplitude of ICP (AMP) and MAP, RAC-correlation between AMP and cerebral
      perfusion pressure (CPP)], B. TCD derived (Mx-correlation between mean flow
      velocity (FVm) and CPP, Mx_a-correlation between FVm and MAP, Sx-correlation
      between systolic flow velocity (FVs) and CPP, Sx_a-correlation between FVs and
      MAP, Dx-correlation between diastolic flow index (FVd) and CPP, Dx_a-correlation
      between FVd and MAP], and LDF derived (Lx-correlation between LDF cerebral blood
      flow [CBF] and CPP, Lx_a-correlation between LDF-CBF and MAP). We assessed the
      relationship between these indices via Pearson correlation, Friedman test,
      principal component analysis (PCA), agglomerative hierarchal clustering (AHC),
      and k-means cluster analysis (KMCA). RESULTS: LDF-based autoregulatory index (Lx)
      was most associated with TCD-based Mx/Mx_a and Dx/Dx_a across Pearson
      correlation, PCA, AHC, and KMCA. Lx was only remotely associated with ICP-based
      indices (PRx, PAx, RAC). TCD-based Sx/Sx_a was more closely associated with ICP
      derived PRx, PAx and RAC. This indicates that vascular-derived indices of
      autoregulatory capacity (i.e., TCD and LDF based) covary, with Sx/Sx_a being the
      exception, whereas indices of cerebrovascular reactivity derived from pulsatile
      CBV (i.e., ICP indices) appear to not be closely related to those of vascular
      origin. CONCLUSIONS: Transcranial Doppler Mx is the most closely associated with
      LDF-based Lx/Lx_a. Both Sx/Sx-a and the ICP-derived indices appear to be
      dissociated with LDF-based cerebrovascular reactivity, leaving Mx/Mx-a as a
      better surrogate for the assessment of cortical small vessel/MV cerebrovascular
      reactivity. Sx/Sx_a cocluster/covary with ICP-derived indices, as seen in our
      previous work.

PMID- 29043545
TI  - Early Brain Injury Associated with Systemic Inflammation After Subarachnoid
      Hemorrhage.
AB  - BACKGROUND: Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage
      (aSAH) is defined as brain injury occurring within 72 h of aneurysmal rupture.
      Although EBI is the most significant predictor of outcomes after aSAH, its
      underlying pathophysiology is not well understood. We hypothesize that EBI after
      aSAH is associated with an increase in peripheral inflammation measured by
      cytokine expression levels and changes in associations between cytokines.
      METHODS: aSAH patients were enrolled into a prospective observational study and
      were assessed for markers of EBI: global cerebral edema (GCE), subarachnoid
      hemorrhage early brain edema score (SEBES), and Hunt-Hess grade. Serum samples
      collected at <= 48 h of admission were analyzed using multiplex bead-based assays
      to determine levels of 13 pro- and anti-inflammatory cytokines. Pairwise
      correlation coefficients between cytokines were represented as networks. Cytokine
      levels and differences in correlation networks were compared between EBI groups.
      RESULTS: Of the 71 patients enrolled in the study, 17 (24%) subjects had GCE, 31
      (44%) subjects had SEBES >= 3, and 21 (29%) had HH >= 4. IL-6 was elevated in
      groups with GCE, SEBES >= 3, and HH >= 4. MIP1beta was independently associated
      with high-grade SEBES. Correlation network analysis suggests higher systematic
      inflammation in subjects with SEBES >= 3. CONCLUSIONS: EBI after SAH is
      associated with increased levels of specific cytokines. Peripheral levels of IL
      10, IL-6, and MIP1beta may be important markers of EBI. Investigating systematic
      correlations in addition to expression levels of individual cytokines may offer
      deeper insight into the underlying mechanisms related to EBI.

PMID- 29043546
TI  - Compensatory-Reserve-Weighted Intracranial Pressure and Its Association with
      Outcome After Traumatic Brain Injury.
AB  - OBJECTIVE: We introduced 'compensatory-reserve-weighted intracranial pressure
      (ICP),' named 'weightedICP' for brevity, as a variable that may better describe
      changes leading to mortality after traumatic brain injury (TBI) over the standard
      mean ICP. METHODS: ICP was monitored prospectively in over 1023 sedated and
      ventilated patients. The RAP coefficient (R-correlation, A-amplitude, and P
      pressure) was calculated as the running correlation coefficient between slow
      changes in the pulse amplitude of ICP and the mean ICP. RAP has a value of 0 on
      the linear part of the pressure-volume curve and a value of + 1 on the ascending
      exponential part. Then, RAP decreases towards zero or even becomes negative when
      ICP increases further-a phenomenon thought to be related to the critical closing
      of cerebral vessels. In this study, we investigated a derived variable called
      weightedICP, calculated as ICP*(1 - RAP). RESULTS: Mortality after TBI was
      associated with both elevated ICP and weightedICP. Analysis of variance showed
      higher values of test statistics for weightedICP (K = 93) than for ICP (K = 64)
      in outcome categorization. Additionally, receiver operator curve analysis
      indicated greater area under the curve for weightedICP (0.71) than for ICP (0.67)
      with respect to associated mortality; however, the difference was not
      statistically significant (p = 0.12). The best threshold (maximizing sensitivity
      and specificity) was 19.5 mm Hg for mean ICP, and 8 mm Hg for weightedICP.
      Mortality rate expressed as a function of mean ICP and weightedICP showed an
      ascending profile in both cases. CONCLUSION: The proposed variable shows a
      significant association with mortality following head injury. It is sensitive to
      both the rising absolute ICP and to the critical deterioration of pressure-volume
      compensation.

PMID- 29043547
TI  - Age-Related Effects of Bariatric Surgery on Early Atherosclerosis and
      Cardiovascular Risk Reduction.
AB  - BACKGROUND: Carotid intima-media thickness (CIMT) is increasingly used as a
      prognostic indicator for early atherosclerosis and the development of
      cardiovascular disease. The objective of this study is to assess the exact
      effects of bariatric surgery on CIMT reduction in different age groups. METHODS:
      CIMT was measured just proximal to the bifurcation of the carotid artery in 166
      patients with mean body mass index of 43.4 kg/m2 before and at 6 and 12 months
      after bariatric surgery. Preoperative CIMT and Framingham Risk Score (FRS) were
      compared to measurements at 6 and 12 months, postoperatively. Impact of age on
      CIMT change and cardiovascular risk reduction was analyzed. RESULTS: Median
      follow-up was 12 months; 12% were lost to follow-up. Mean CIMT values at 12
      months after bariatric surgery were significantly lower compared to baseline
      (0.619 vs. 0.587 mm, p = 0.005 in women and 0.675 vs. 0.622 mm, p = 0.037 in men,
      respectively), and these effects were statistically significant in all age
      groups. The mean reduction of CIMT for patients < 50 years at 12 months was 0.043
      mm (- 7.0%), while CIMT was reduced with 0.013 mm for patients >= 50 years (-
      1.9%, p = 0.022). At 12 months after bariatric surgery, FRS had decreased with
      52% in patients < 50 years as compared with 35% in patients >= 50 years (p =
      0.025). CONCLUSIONS: Bariatric surgery resulted in a significant CIMT decrease in
      patients with morbid obesity in all evaluated age categories. These beneficial
      effects of bariatric surgery were more pronounced in younger patients, while
      cardiovascular risk reduction by bariatric surgery appeared inferior in patients
      of 50 years and older.

PMID- 29043548
TI  - Comparison of Short-Term Effectiveness and Postoperative Complications:
      Laparoscopic Gastric Plication vs Laparoscopic Sleeve Gastrectomy.
AB  - INTRODUCTION: Bariatric surgeries are the only effective long-term treatment in
      obese patients. The innovation of laparoscopic gastric plication (LGP) raised
      some questions about its effectiveness compared to traditionally used techniques
      such as laparoscopic sleeve gastrectomy (LSG). We tried to answer some of these
      questions. MATERIALS AND METHODS: We investigated 70 patients in a randomized
      clinical trial (IRCT2013123012294N5) from 2012 to 2015. Thirty-five patients were
      randomly assigned to each LSG or LGP group, using sealed envelope method. The
      body mass index (BMI) reduction and the percentage of excess weight loss (%EWL)
      along with %total body weight loss (%TWL) were primary endpoint and were assessed
      at follow-up periods. We recorded postoperative complications, as well. RESULTS:
      Two-year follow-up rate was 100%. There were no statistically significant
      differences between the two groups in means of preoperative BMI. Also,
      postoperative follow-ups were not suggestive for a significant difference in BMI
      (all p values > 0.05). The mean %EWL at follow-ups showed no significant
      difference at any point, except for 3 and 6 months after surgery (p value = 0.002
      and 0.017, respectively). This finding was confirmed by %TWL trend in 12 months
      after surgery. LSG patients were readmitted more than LGP patients (seven cases
      vs one case, p value = 0.024). Postoperative complications such as nausea and
      vomiting, hair loss, iron deficiency, vitamin D deficiency, and cholelithiasis
      were not different between the two groups. There was one death in the LGP group
      due to pulmonary thromboembolism. CONCLUSIONS: LGP showed to be efficient
      regarding %EWL and %TWL reduction in short-term follow-ups with comparable
      postoperative complications to LSG.

PMID- 29043549
TI  - Prevalence and Predictors of Gastroesophageal Reflux Disease After Laparoscopic
      Sleeve Gastrectomy.
AB  - BACKGROUND AND AIMS: Laparoscopic sleeve gastrectomy (LSG) might be associated
      with a new onset or worsening of gastroesophageal reflux disease (GERD). We aim
      to evaluate the prevalence of post-LSG GERD symptoms and its predictors. METHODS:
      We included patients who underwent primary LSG at a university hospital from 2009
      to 2015. We used the GERD-Health-Related Quality of Life (GERD-HRQL)
      questionnaire and included questions regarding regurgitation to evaluate symptoms
      before and after LSG; each item was scored from 1 to 5 based on the symptom
      severity. RESULTS: A total of 213 patients (mean age, 36.08 +/- 10.22 years;
      48.36% were men) were included. The mean preoperative body mass index (BMI) was
      47.84 kg/m2, mean percent total weight loss was 37.99% (95% CI, 36.64 to 39.34),
      mean percent excess weight loss was 84.14% (95% CI, 80.91 to 87.36), and the mean
      percent excess BMI loss was 84.17% (95% CI, 80.94 to 87.41). The mean heartburn
      score while standing increased (0.71 vs. 1.09, p < 0.01) as well as the score of
      heartburn requiring a diet change (0.67 vs. 1.16, p < 0.01) post-LSG. The scores
      for dysphagia, odynophagia, and regurgitation increased. New-onset heartburn was
      reported in 47.06% of our cohort. Those with high preoperative BMIs were less
      likely to develop new-onset or worsening symptoms of GERD (odds ratio [OR], 0.97;
      95% confidence interval [CI], 0.95-0.99). More severe heartburn symptoms while
      standing were associated with higher risks of developing or worsening GERD
      symptoms (OR, 1.22; 95% CI, 1.01-1.47). None of the other variables could predict
      the development or worsening of the GERD symptoms. CONCLUSION: Symptoms of
      heartburn and regurgitation are common after LSG; however, none of the variables
      preoperatively could strongly predict patients who would develop new onset or
      experience worsening of symptoms postoperatively.

PMID- 29043550
TI  - Collision of metastatic malignant melanoma and acute myelogenous leukemia in the
      bone marrow.

PMID- 29043552
TI  - The future of nuclear cardiac imaging: Reflection and a vision.

PMID- 29043553
TI  - What is this image? 2017: image 3 result : Incidental findings during myocardial
      perfusion imaging.

PMID- 29043551
TI  - MAGI-1 expression is decreased in several types of human T-cell leukemia cell
      lines, including adult T-cell leukemia.
AB  - Membrane-associated guanylate kinase with inverted orientation protein 1 (MAGI-1)
      is a cytoplasmic scaffold protein that interacts with various signaling
      molecules; it negatively controls the cell growth of various types of cells and
      positively controls cell-cell interaction. In T cells, MAGI-1 has been shown to
      inhibit Akt activity through its interaction with PTEN and MEK1. In this study we
      found that MAGI-1 expression is decreased in multiple (9 out of 15) human T-cell
      leukemia cell lines, including adult T-cell leukemia (ATL), T-cell acute
      lymphoblastic leukemia and chronic T-cell lymphocytic leukemia. The
      overexpression of MAGI-1 protein in a MAGI-1-low ATL cell line reduced cellular
      growth. While the overexpression of MAGI-1 protein in a MAGI-1-low ATL cell line
      reduced the Akt and MEK activities, the knockdown of MAGI-1 in a MAGI-1-high ATL
      cell line augmented the Akt and MEK activities. Collectively, the findings of the
      present study suggest that the decreased expression of MAGI-1 in human T cells
      contributes to the development of several types of T-cell leukemia, partly
      through the stimulation of the Akt and MEK pathways.

PMID- 29043554
TI  - Evaluation of left ventricular mass on cadmium-zinc-telluride imaging: Validation
      against cardiac magnetic resonance.
AB  - BACKGROUND: Single-photon emission computed tomography has shown relevant
      limitations in the quantification of left ventricular (LV) mass. We sought to
      compare the estimates of LV mass on Cadmium-Zinc-Telluride (CZT) myocardial
      perfusion imaging (MPI) as compared to cardiac magnetic resonance (CMR). METHODS
      AND RESULTS: Twenty-five patients underwent MPI on a CZT camera and CMR on a 1.5
      T scanner within 12 +/- 3 weeks. LV mass was quantified on CZT images using two
      softwares: 4D-MSPECT (4DM) and Emory Cardiac Toolbox (ECTb). LV mass by CMR was
      quantified using MASS software (Medis, Leiden, The Netherlands). LV mass values
      obtained with 4DM and ECTb were highly reproducible [intraclass correlation
      coefficients .98 (95% CI .97-.99), and .98 (95% CI 0.97-.99), respectively]. The
      mean LVM mass values were 151 +/- 44 g on CMR, 151 +/- 43 g with 4DM (P = NS vs
      CMR), and 157 +/- 42 g with ECTb (P < .001 vs CMR; P = .007 vs 4DM) CZT images.
      There was an excellent correlation between LV mass values between CMR and both
      4DM (R 2 = .95; P < .001) and ECTb (R 2 = .98; P < .001) with narrow limits of
      agreement (- 13.6% to + 13.4% for 4DM, and - 5.6% to + 14.1% for ECTb).
      CONCLUSIONS: The evaluation of LV mass is feasible on CZT images, showing
      excellent agreement with CMR.

PMID- 29043555
TI  - Impact of non-specific normal databases on perfusion quantification of low-dose
      myocardial SPECT studies.
AB  - AIM: To evaluate the impact of non-specific normal databases on the percent
      summed rest score (SR%) and stress score (SS%) from simulated low-dose SPECT
      studies by shortening the acquisition time/projection. METHODS: Forty normal
      weight and 40 overweight/obese patients underwent myocardial studies with a
      conventional gamma-camera (BrightView, Philips) using three different acquisition
      times/projection: 30, 15, and 8 s (100%-counts, 50%-counts, and 25%-counts scan,
      respectively) and reconstructed using the iterative algorithm with resolution
      recovery (IRR) AstonishTM (Philips). Three sets of normal databases were used:
      (1) full-counts IRR; (2) half-counts IRR; and (3) full-counts traditional
      reconstruction algorithm database (TRAD). The impact of these databases and the
      acquired count statistics on the SR% and SS% was assessed by ANOVA analysis and
      Tukey test (P < 0.05). RESULTS: Significantly higher SR% and SS% values (> 40%)
      were found for the full-counts TRAD databases respect to the IRR databases. For
      overweight/obese patients, significantly higher SS% values for 25%-counts scans
      (+19%) are confirmed compared to those of 50%-counts scan, independently of using
      the half-counts or the full-counts IRR databases. CONCLUSIONS: AstonishTM
      requires the adoption of the own specific normal databases in order to prevent
      very high overestimation of both stress and rest perfusion scores. Conversely,
      the count statistics of the normal databases seems not to influence the
      quantification scores.

PMID- 29043556
TI  - Incidence of atrioventricular block with vasodilator stress SPECT: A meta
      analysis.
AB  - BACKGROUND: Adenosine or regadenoson are often used with pharmacologic stress
      testing. Adenosine may trigger atrioventricular block (AVB). Despite its higher
      selectivity, regadenoson has also been associated with AVB. We studied the
      incidence of de novo AVB with these agents. METHODS: A comprehensive search of
      SCOPUS was performed from inception to March 2016. Studies of at least 10
      patients, using adenosine and/or regadenoson with SPECT-MPI, reporting rates of
      AVB were selected for further review. RESULTS: Thirty four studies were pooled
      including 22,957 patients. Adenosine was used in 21 studies and regadenoson in
      15. Both were administered in two studies. The estimated incidence of overall and
      high-grade AVB was 3.81% (95% CI 1.99%-6.19%) and 1.93% (95% CI 0.77%-3.59%),
      respectively. The incidence of AVB (8.58%; 95% CI 5.55%-12.21% vs 0.30%; 95% CI
      0.04%-0.82%, respectively, P < .001) and high-grade AVB (5.21%; 95% CI 2.81%
      8.30% vs 0.05%; 95% CI < .001%-0.19% respectively, P < .001) were higher with
      adenosine compared to regadenoson. CONCLUSION: AVB is seen in about 4% of
      patients undergoing vasodilator stress test. Both overall and high-grade AVB are
      more frequent with adenosine compared to regadenoson.

PMID- 29043558
TI  - Enriched Expression of Neutral Sphingomyelinase 2 in the Striatum is Essential
      for Regulation of Lipid Raft Content and Motor Coordination.
AB  - Sphingomyelinases are a family of enzymes that hydrolyze sphingomyelin to
      generate phosphocholine and ceramide. The brain distribution and function of
      neutral sphingomyelinase 2 (nSMase2) were elucidated in this study. nSMase2 mRNA
      expression was greatest in the striatum, followed by the prefrontal cortex,
      hippocampus, cerebellum, thalamus, brainstem, and olfactory bulb. The striatum
      had the highest level of nSMase2 protein expression, followed by the prefrontal
      cortex, thalamus, hippocampus, brainstem, and cerebellum. Dense immunolabeling
      was observed in the striatum, including the caudate-putamen, while moderately
      dense staining was found in the olfactory bulb and cerebral neocortex. Electron
      microscopy of the caudate-putamen showed nSMase2 immunoreaction product was
      present in small diameter dendrites or dendritic spines, that formed asymmetrical
      synapses with unlabeled axon terminals containing small round vesicles; and
      characteristics of glutamatergic axons. Lipidomic analysis of the striatum showed
      increase in long chain sphingomyelins, SM36:1 and SM38:1 after inhibition of
      nSMase activity. Quantitative proteomic analysis of striatal lipid raft fraction
      showed many proteins were downregulated by more than 2-fold after inhibition or
      antisense knockdown of nSMase; consistent with the notion that nSMase2 activity
      is important for aggregation or clustering of proteins in lipid rafts. Inhibition
      or antisense knockdown of nSMase2 in the caudate-putamen resulted in motor
      deficits in the rotarod and narrow beam tests; as well as decreased acoustic
      startle and improved prepulse inhibition of the startle reflex. Together, results
      indicate an important function of nSMase2 in the striatum.

PMID- 29043559
TI  - Nonfunctioning adrenal incidentaloma affecting central blood pressure and
      arterial stiffness parameters.
AB  - PURPOSE: Recently, cardiovascular risk is thought to be increased in patients
      with nonfunctioning adrenal incidentaloma (NFAI). There are no sufficient studies
      in the literature to evaluate this situation in NFAI patients without
      cardiovascular risk. The objective of this study is to compare peripheral and
      central blood pressure and arterial stiffness between patients with NFAI and
      healthy volunteers (of a similar age, gender and body mass index as the NFAI
      group) who have no traditional cardiovascular risk factors and autonomous
      cortisol secretion, with pulse wave analysis (PWA). METHODS: In this cross
      sectional study, we evaluated 35 NFAI patients who have no traditional
      cardiovascular risk factors and 35 healthy volunteers. PWA was performed in the
      participants of similar gender, age and body mass index, with a Mobil-O-Graph
      PWA/ABPM (I.E.M. GmBH, Stolberg, Germany) device. Radiological and biochemical
      data were obtained retrospectively in the NFAI group. RESULTS: In our study,
      systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial
      pressure (MAP), central SBP, central DBP, peripheral vascular resistance,
      augmentation pressure (AP), heart rate-corrected augmentation index (Aix@75) and
      pulse wave velocity (PWV) values were significantly higher in the NFAI group
      compared to the control group. In addition, peripheral and central blood pressure
      and arterial stiffness parameters were correlated with age and duration of NFAI
      diagnosis of more than 1 year. CONCLUSIONS: NFAIs are known as
      cardiometabolically innocent, but in our study, both peripheral and central blood
      pressure values and arterial stiffness parameters were negatively affected in
      patients diagnosed with NFAI who have no traditional cardiovascular risk factors.
      These patients are at risk of cardiovascular diseases.

PMID- 29043557
TI  - A joint procedural position statement on imaging in cardiac sarcoidosis: from the
      Cardiovascular and Inflammation & Infection Committees of the European
      Association of Nuclear Medicine, the European Association of Cardiovascular
      Imaging, and the American Society of Nuclear Cardiology.

PMID- 29043560
TI  - Optimal timing of dopamine agonist withdrawal in patients with
      hyperprolactinemia: a systematic review and meta-analysis.
AB  - PURPOSE: Dopamine agonists (DAs) are recommended as first-line treatment for
      patients with hyperprolactinemia. Generally, it is accepted that patients with
      hyperprolactinemia do not need lifelong medication, but the optimal timing for DA
      withdrawal has not been determined. The aim of this systematic review and meta
      analysis is to assess the impact of DA withdrawal on the clinical outcomes of
      patients with hyperprolactinemia, and to explore possible factors affecting
      successful DA withdrawal. METHODS: The databases of PubMed, Cochrane and EMBASE
      were searched up to May 2016. RESULTS: The proportion of patients with persisting
      normoprolactinemia after DA withdrawal reached 36.6% in a random effects model
      (95% CI, 29.4-44.2%; I-squared: 82.5%). Data of stratified analysis showed that
      the success rate of drug withdrawal was high in patients using cabergoline (CAB)
      as the only treatment (41.2%; 95% CI 32.3-50.4%) and those using CAB over 24
      months (48.7%; 95% CI 38.9-58.5%), especially in patients with idiopathic
      hyperprolactinemia (73.2%; 95% CI 55.6-87.7%). In addition, patients who received
      a low maintenance dose of CAB, and had a significant reduction in tumor size
      (over 50%) before withdrawal, were more likely to achieve success (51.5 and
      49.4%, respectively). CONCLUSION: The success rate of DA withdrawal has increased
      in recent years. Further, the success rate of CAB withdrawal was higher than that
      of bromocriptine, especially in patients with a duration of treatment longer than
      24 months. Conclusively, the probability of success was higher in patients who
      received low-dose CAB maintenance treatment and those who achieved a significant
      reduction in tumor size before withdrawal.

PMID- 29043561
TI  - Clinical profile of silent growth hormone pituitary adenomas; higher recurrence
      rate compared to silent gonadotroph pituitary tumors, a large single center
      experience.
AB  - PURPOSE: Study and comparison of characteristics of silent growth hormone
      adenomas (SGHA), silent corticotroph adenomas (SCA), and silent gonadotroph
      adenomas (SGA) in a single institution cohort of surgically treated pituitary
      adenomas. METHODS: Retrospective analysis of SGHA surgically resected over 10
      years: SGHA was defined as no clinical or biochemical evidence of acromegaly and
      positive GH immunostaining. RESULTS: Of 814 pituitary surgeries; 2.1% (n = 17)
      were SGHA, 4.5% (n = 37) SCA, and 18.9% (n = 70/371; 2011-2016) SGA. Mean age at
      SGHA diagnosis was 43 years, with a large female predominance (82%). Mean tumor
      size and cavernous/sphenoid sinus invasiveness for SGHA, SCA, and SGA were 1.5 +/
      1.0 cm and 25%, 2.5 +/- 1.2 cm and 43%, 2.9 +/- 2.0 cm and 41%, respectively
      (tumor size p = 0.009, SGHA vs. SGA, and invasion p; not-significant). During
      mean follow-up of 3.9 years, two patients (11%) developed elevated insulin-like
      growth factor-1 and five patients (29%) required a second surgery for tumor
      recurrence. Rate of surgical reintervention was similar to SCA (31%), but higher
      than SGA (10%) (p = 0.035, SGHA vs. SGA), and 18% underwent radiation therapy,
      similar to SCA (19%, p; not-significant) but higher than SGA (2.9%, p = 0.018).
      CONCLUSION: This is the largest single center study characterizing SGHA behavior
      with SGA and SCA control groups in a cohort of surgically resected pituitary
      adenomas. SGHA present mostly in young females, and should be closely followed
      due to their higher likelihood of recurrence and potential of progression to
      clinical acromegaly. We propose that a complete hormonal staining panel be
      routinely performed for all pituitary adenomas.

PMID- 29043562
TI  - A review of the management of tibial plateau fractures.
AB  - Tibial plateau fractures form a wide spectrum of injuries presenting varying
      challenges to the trauma surgeon. The prognosis of this injury spectrum is
      largely dependent on the management of each particular configuration, and the
      literature is as a result littered with a number of management strategies with
      limited consensus. The aim of this review is to provide a concise guide to the
      trauma surgeon based on newer and classical peer-reviewed publications in
      international orthopaedic journals. A PubMed search was conducted to identify
      peer-reviewed publications within the last 10 years and expanded to identify
      classic papers pertaining to the Schatzker classification. The focus was on
      articles based on management techniques, controversies and recent developments.
      The management of specific injury patterns is based on the Schatzker
      classification which is a widely accepted traditional classification system.
      Whilst there is a general consensus on the ultimate goal of a stable anatomic
      reduction in this subset of fractures, there continues to be a number of
      controversies surrounding issues including pre-operative imaging, initial
      assessment and definitive management of specific injury patterns, some of which
      do not conform to the original Schatzker classification. The majority of
      fractures will require operative management, and with whatever management
      strategy employed, the main emphasis is on respecting the soft tissue envelope.
      There remains a paucity of prospective randomised controlled trials comparing the
      different available operative techniques.

PMID- 29043563
TI  - Malformation of the Posterior Cerebellar Vermis Is a Common Neuroanatomical
      Phenotype of Genetically Engineered Mice on the C57BL/6 Background.
AB  - C57BL/6 mice exhibit spontaneous cerebellar malformations consisting of
      heterotopic neurons and glia in the molecular layer of the posterior vermis,
      indicative of neuronal migration defect during cerebellar development.
      Recognizing that many genetically engineered (GE) mouse lines are produced from
      C57BL/6 ES cells or backcrossed to this strain, we performed histological
      analyses and found that cerebellar heterotopia were a common feature present in
      the majority of GE lines on this background. Furthermore, we identify GE mouse
      lines that will be valuable in the study of cerebellar malformations including
      diverse driver, reporter, and optogenetic lines. Finally, we discuss the
      implications that these data have on the use of C57BL/6 mice and GE mice on this
      background in studies of cerebellar development or as models of disease.

PMID- 29043565
TI  - Eccentric Macular Hole after Pars Plana Vitrectomy for Epiretinal Membrane
      Without Internal Limiting Membrane Peeling: A Case Report.
AB  - INTRODUCTION: Postoperative eccentric macular hole formation is an uncommon
      complication after pars plana vitrectomy (PPV) without internal limiting membrane
      (ILM) peeling for the treatment of epiretinal membrane (ERM). We present a case
      of eccentric macular hole formation after PPV for ERM without ILM peeling. CASE
      REPORT: A 68-year-old male patient presented with ERM and visual acuity of 6/24
      in his left eye. He underwent 23-gauge PPV without ILM peeling for treatment of
      ERM. One week postoperatively the retina was attached and the epiretinal membrane
      was successfully removed, while visual acuity was 6/9. One month after PPV, a
      single eccentric retinal hole below the macula was detected using fundoscopy and
      subsequently confirmed by optical coherence tomography. At this time the visual
      acuity was 6/9 and the patient reported no symptoms. No further intervention was
      attempted and at the 9-month follow-up, the visual acuity and the size of the
      eccentric macular hole remained stable. CONCLUSION: Eccentric macular holes can
      be developed after PPV even without ILM peeling and are usually managed
      conservatively by observation.

PMID- 29043564
TI  - The UCP2-866G/A Polymorphism Could be Considered as a Genetic Marker of Different
      Functional Prognosis in Ischemic Stroke After Recanalization.
AB  - Recent studies based on experimental animal models of stroke have suggested that
      uncoupling protein 2 (UCP2), an inner mitochondrial membrane protein that is
      thought to regulate energy metabolism and reduce reactive oxygen species
      generation, provides protection against reperfusion damage. We aimed to
      investigate whether -866G/A polymorphism in the promoter of the UCP2 gene, which
      enhances its transcriptional activity, is associated with functional prognosis in
      patients with embolic ischemic stroke after early recanalization. We investigate
      a hospital-based prospective cohort of patients with acute ischemic stroke due to
      occlusion of the middle cerebral artery diagnosed by transcranial Doppler who
      obtained a partial/complete recanalization 24 h after administration of
      intravenous thrombolysis. The main end point of the study was functional
      independence defined as modified Rankin Scale 0-2 on day 90. A total of 80
      patients were enrolled. The UCP2-866G/A polymorphism was determined by polymerase
      chain reaction-restriction fragment length polymorphism technique (14 genotype
      A/A (18%), 45 genotype A/G (56%) and 21 genotype G/G (26%). The percentage of
      patients with good functional outcome at 3 months was significantly higher in
      patients harboring the A/A genotype than in those with A/G or G/G genotypes (85
      vs 41%, p = 0.01). The A/A genotype was found to be an independent marker of good
      prognosis after adjustment for secondary variables (age, sex, glucose level,
      NIHSS score at baseline, complete recanalization and early neurological
      improvement) in a logistic regression analysis (OR 0.05, 95% CI 0.01-0.48, p =
      0.01). Our results suggest that the AA genotype of UCP2-866 may predict a better
      functional outcome in ischemic stroke after recanalization of proximal MCA
      occlusion.

PMID- 29043566
TI  - Clinical Evaluation and Physical Exam Findings in Patients with Anterior Shoulder
      Instability.
AB  - PURPOSE OF REVIEW: The goal of this paper is to provide an overview in evaluating
      the patient with suspected or known anteroinferior glenohumeral instability.
      RECENT FINDINGS: There is a high rate of recurrent subluxations or dislocations
      in young patients with history of anterior shoulder dislocation, and recurrent
      instability will increase likelihood of further damage to the glenohumeral joint.
      Proper identification and treatment of anterior shoulder instability can
      dramatically reduce the rate of recurrent dislocation and prevent subsequent
      complications. Overall, the anterior release or surprise test demonstrates the
      best sensitivity and specificity for clinically diagnosing anterior shoulder
      instability, although other tests also have favorable sensitivities,
      specificities, positive likelihood ratios, negative likelihood ratios, and inter
      rater reliabilities. Anterior shoulder instability is a relatively common injury
      in the young and athletic population. The combination of history and performing
      apprehension, relocation, release or surprise, anterior load, and anterior drawer
      exam maneuvers will optimize sensitivity and specificity for accurately
      diagnosing anterior shoulder instability in clinical practice.

PMID- 29043567
TI  - Impact of Adverse Events on Health Utility and Health-Related Quality of Life in
      Patients Receiving First-Line Chemotherapy for Metastatic Breast Cancer: Results
      from the SELECT BC Study.
AB  - OBJECTIVE: The aim of this study was to investigate the impact of adverse events
      (AEs) on health utility and health-related quality of life (HRQOL) in patients
      with metastatic breast cancer undergoing first-line chemotherapy. METHODS: We
      analyzed the data from the SELECT BC study, a multicenter, open-label,
      randomized, phase III study conducted in Japan, which compared first-line S-1
      with taxane therapies. Heath utility and HRQOL were assessed using the EQ-5D-3L
      and European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire Core 30 (EORTC QLQ-C30) at baseline and 3, 6, and 12 months after
      treatment initiation. Health utility was calculated based on societal
      preferences, and AEs were reported at each cycle of the study treatment. Linear
      marginal mean models were used to quantify the impact of the last AEs (with 10 or
      more incidences) observed before HRQOL assessment on health utility and HRQOL.
      RESULTS: Analysis included 380 patients and 12 (of 15) AEs. Grade 1 nausea and
      oral mucositis, grade 1 and 2 edema, and grade 2 fatigue, motor and sensory
      neuropathy, and myalgia were significantly associated with disutility, measured
      using the EQ-5D-3L. Grade 1 oral mucositis, grade 1 and 2 fatigue, and grade 2
      sensory neuropathy were significantly associated with impaired global health
      status in the EORTC QLQ-C30. AEs associated with decrements in the five
      functioning scales included fatigue, oral mucositis, nausea, edema, motor and
      sensory neuropathy, and myalgia. CONCLUSIONS: We reported disutilities caused by
      AEs in patients with metastatic breast cancer under chemotherapy. These findings
      can be applied to future model-based cost-effectiveness analyses. TRIAL
      REGISTRATION NUMBER: C000000416.

PMID- 29043568
TI  - Intensified neoadjuvant multimodal approach in synchronous liver metastases from
      gastric cancer: a single institutional experience.
AB  - BACKGROUND: Synchronous liver metastases (LM) from gastric (GC) or
      esophagogastric junction (EGJ) adenocarcinoma are a rare events. Several trials
      have evaluated the role of liver surgery in this setting, but the impact of
      preoperative therapy remains undetermined. METHODS: Patients with synchronous LM
      from GC/EGJ adenocarcinoma who achieved disease control after induction
      chemotherapy (ICT) and were subsequently scheduled to chemoradiotherapy (CRT) to
      the primary tumor and surgery assessment were retrospectively analyzed.
      Pathological response, patterns of relapse, progression-free survival (PFS), and
      overall survival (OS) were calculated. From July 2002 to September 2012, 16
      patients fulfilling the inclusion criteria were identified. RESULTS: Primary
      tumor site was GC (nine patients) or EGJ (seven patients). LM were considered
      technically unresectable in nine patients. Radiological response to the whole
      neoadjuvant program was achieved in 13 patients. Eight patients underwent
      surgical resection of the primary tumor; in five of these LM were resected. A
      complete pathological response in the primary or in the LM was found in four and
      three patients, respectively. The most frequent site of relapse/progression was
      systemic (eight patients). Local and liver-only relapses were observed in two
      patients each. After a median follow-up of 91 months, the median OS and PFS were
      23.0 (95% CI 13.2-32.8) and 17.0 months (95% CI 11.7-22.3). 5-year actuarial PFS
      is 17.6%. CONCLUSION: Our results suggest that an intensified approach using ICT
      followed by CRT in synchronous LM from GC/EGJ adenocarcinoma is feasible and may
      translate into prolonged survival times in selected patients.

PMID- 29043569
TI  - Nutritional support and parenteral nutrition in cancer patients: an expert
      consensus report.
AB  - BACKGROUND: Malnutrition is a frequent medical problem of cancer patients that
      negatively impacts their quality of life. METHODS: A multidisciplinary group of
      experts in Medical Oncology, Pharmacy, and Nutrition convened to discuss the
      management of the nutritional support in cancer patients. RESULTS: Of the 18
      questions addressed, 9 focused on nutritional support, 5 were related to
      parenteral nutrition (PN) and 4 about home PN (HPN). The panel of experts
      recommends using nutritional screening routinely, at diagnosis and throughout the
      disease course, for detecting the risk of malnutrition and, if it is positive, to
      perform a complete nutritional assessment, to diagnose malnutrition. Currently,
      there are different screening tools and methods that allow us to detect
      nutritional risk. Based on the evidence and experience, the panel stated that PN
      is indicated mainly when it is not possible to use the digestive tract and/or
      oral feeding and/or enteral nutrition is not sufficient or possible. The
      nutritional needs of the cancer patients, except in those cases where
      individualized measures are required, should be considered similar to healthy
      individuals (25-30 kcal/kg/day). The panel considers that the nutritional
      monitoring of the cancer patient should be multidisciplinary and adapted to the
      characteristics of each center. Additionally, the objective of the HPN is to
      improve or maintain the nutritional status of a patient at home. CONCLUSIONS:
      This document seeks to lay down a set of recommendations and to identify key
      issues that may be useful for the nutritional management of cancer patients.

PMID- 29043571
TI  - An uncertainty-based framework to quantifying climate change impacts on coastal
      flood vulnerability: case study of New York City.
AB  - The continued development efforts around the world, growing population, and the
      increased probability of occurrence of extreme hydrologic events have adversely
      affected natural and built environments. Flood damages and loss of lives from the
      devastating storms, such as Irene and Sandy on the East Coast of the USA, are
      examples of the vulnerability to flooding that even developed countries have to
      face. The odds of coastal flooding disasters have been increased due to
      accelerated sea level rise, climate change impacts, and communities' interest to
      live near the coastlines. Climate change, for instance, is becoming a major
      threat to sustainable development because of its adverse impacts on the
      hydrologic cycle. Effective management strategies are thus required for flood
      vulnerability reduction and disaster preparedness. This paper is an extension to
      the flood resilience studies in the New York City coastal watershed. Here, a
      framework is proposed to quantify coastal flood vulnerability while accounting
      for climate change impacts. To do so, a multi-criteria decision making (MCDM)
      approach that combines watershed characteristics (factors) and their weights is
      proposed to quantify flood vulnerability. Among the watershed characteristics,
      potential variation in the hydrologic factors under climate change impacts is
      modeled utilizing the general circulation models' (GCMs) outputs. The considered
      factors include rainfall, extreme water level, and sea level rise that exacerbate
      flood vulnerability through increasing exposure and susceptibility to flooding.
      Uncertainty in the weights as well as values of factors is incorporated in the
      analysis using the Monte Carlo (MC) sampling method by selecting the best-fitted
      distributions to the parameters with random nature. A number of low impact
      development (LID) measures are then proposed to improve watershed adaptive
      capacity to deal with coastal flooding. Potential range of current and future
      vulnerability to flooding is estimated with and without consideration of climate
      change impacts and after implementation of LIDs. Results show that climate change
      has the potential to increase rainfall intensity, flood volume, floodplain
      extent, and flood depth in the watershed. The results also reveal that improving
      system resilience by reinforcing the adaptation capacity through implementing
      LIDs could mitigate flood vulnerability. Moreover, the results indicate the
      significant effect of uncertainties, arising from the factors' weights as well as
      climate change, impacts modeling approach, on quantifying flood vulnerability.
      This study underlines the importance of developing applicable schemes to quantify
      coastal flood vulnerability for evolving future responses to adverse impacts of
      climate change.

PMID- 29043570
TI  - Towards precision nephrology: the opportunities and challenges of genomic
      medicine.
AB  - The expansion of genomic medicine is furthering our understanding of many human
      diseases. This is well illustrated in the field of nephrology, through the
      characterization, discovery, and growing insight into various renal diseases
      through use of Next Generation Sequencing (NGS) technologies. This review will
      provide an overview of the diagnostic opportunities of using genetic testing in
      the clinical setting by describing notable discoveries regarding inherited forms
      of renal disease that have advanced the field and by highlighting some of the
      potential benefits of establishing a molecular diagnosis in a clinical practice.
      In addition, it will discuss some of the challenges associated with the expansion
      of genetic testing into the clinical setting, including clinical variant
      interpretation and return of genetic results.

PMID- 29043572
TI  - Secreted proteins produced by fungi associated with Botryosphaeria dieback
      trigger distinct defense responses in Vitis vinifera and Vitis rupestris cells.
AB  - Grapevine trunk diseases (Eutypa dieback, esca and Botryosphaeria dieback) are
      caused by a complex of xylem-inhabiting fungi, which severely reduce yields in
      vineyards. Botryosphaeria dieback is associated with Botryosphaeriaceae. In order
      to develop effective strategies against Botryosphaeria dieback, we investigated
      the molecular basis of grapevine interactions with a virulent species,
      Neofusicoccum parvum, and a weak pathogen, Diplodia seriata. We investigated
      defenses induced by purified secreted fungal proteins within suspension cells of
      Vitis (Vitis rupestris and Vitis vinifera cv. Gewurztraminer) with putative
      different susceptibility to Botryosphaeria dieback. Our results show that Vitis
      cells are able to detect secreted proteins produced by Botryosphaeriaceae,
      resulting in a rapid alkalinization of the extracellular medium and the
      production of reactive oxygen species. Concerning early defense responses, N.
      parvum proteins induced a more intense response compared to D. seriata. Early and
      late defense responses, i.e., extracellular medium alkalinization, cell death,
      and expression of PR defense genes were stronger in V. rupestris compared to V.
      vinifera, except for stilbene production. Secreted Botryosphaeriaceae proteins
      triggered a high accumulation of delta-viniferin in V. vinifera suspension cells.
      Artificial inoculation assays on detached canes with N. parvum and D. seriata
      showed that the development of necrosis is reduced in V. rupestris compared to V.
      vinifera cv. Gewurztraminer. This may be related to a more efficient induction of
      defense responses in V. rupestris, although not sufficient to completely inhibit
      fungal colonization. Overall, our work shows a specific signature of defense
      responses depending on the grapevine genotype and the fungal species.

PMID- 29043573
TI  - Structural and physiological responses of Halodule wrightii to ocean
      acidification.
AB  - Coastal areas face high variability of seawater pH. Ocean acidification (OA) and
      local stressors are enhancing this variability, which poses a threat to marine
      life. However, these organisms present potential phenotypic plasticity that can
      offer physiological and structural tools to survive in these extreme conditions.
      In this study, we evaluated the effects of elevated CO2 levels and consequent pH
      reduction on the physiology, anatomy and ultrastructure of the seagrass Halodule
      wrightii. A mesocosm study was conducted in an open system during a 30-day
      experiment, where different concentrations of CO2 were simulated following the
      natural variability observed in coastal reef systems. This resulted in four
      experimental conditions simulating the (i) environmental pH (control condition,
      without CO2 addition) and (ii) reduced pH by - 0.3 units, (iii) - 0.6 units and
      (iv) - 0.9 units, in relation to the field condition. The evaluated population
      only suffered reduced optimum quantum yield (Y(II)), leaf width and cross-section
      area under the lowest CO2 addition (- 0.3 pH units) after 30 days of experiment.
      This fitness commitment should be related to carbon concentration mechanisms
      present in the evaluated species. For the highest CO2 level, H. wrightii
      demonstrated a capacity to compensate any negative effect of the lowest pH. Our
      results suggest that the physiological behaviour of this primary producer is
      driven by the interactions among OA and environmental factors, like irradiance
      and nutrient availability. The observed behaviour highlights that high-frequency
      pH variability and multifactorial approaches should be applied, and when
      investigating the impact of OA, factors like irradiance, nutrient availability
      and temperature must be considered as well.

PMID- 29043575
TI  - Benzenoid Quinodimethanes.
AB  - Reactivity and physical properties of pi-conjugated hydrocarbon systems depend
      predominantly on the topology of pi-electrons array. Quinoidal conjugations serve
      as giving diradical character to molecules, leading to unique chemical behaviors.
      The simplest member of quinodimethanes are o-, m-, and p-quinodimethanes, which
      are very reactive due to diradical character and cannot be isolated under normal
      experimental conditions. However, chemical modifications, such as pi-extension or
      introduction of substituent groups, of quinodimethanes imparts stabilities to
      quinodimethanes that can be handled under ambient conditions. This chapter offers
      an overview of reactivity and magnetic properties of benzenoid o-, m-, and p
      quinodimethanes.

PMID- 29043574
TI  - Characterization and implications of thyroid dysfunction induced by immune
      checkpoint inhibitors in real-life clinical practice: a long-term prospective
      study from a referral institution.
AB  - PURPOSE: Autoimmune diseases are typically associated with immune checkpoints
      blockade. This study aims at assessing, in real-life clinical practice, the
      prevalence and impact of thyroid disorders induced by immune checkpoint
      inhibitors. METHODS: 52 patients (30 F; age 61 +/- 13 years) with advanced
      melanoma treated with ipilimumab (3 mg/kg i.v./3 weeks; 4 doses) were included.
      For disease progression, 29 (16 F) of them received nivolumab (3 mg/kg i.v./2
      weeks) or pembrolizumab (2 mg/kg i.v./3 weeks). Thyroid function and autoimmunity
      were assessed before, after 6 weeks, at the end of ipilimumab, as well as before
      and every 3 months during nivolumab/pembrolizumab treatment. RESULTS: During
      ipilimumab, 7 (4 F) patients developed thyroid dysfunction (4 thyroiditis, 1
      associated with hypothyroidism; 2 thyrotoxicosis in a previously euthyroid
      multinodular goiter; 1 hypothyroidism worsened). During PD1 inhibitors, 7
      patients (3 F) developed hypothyroidism with severe manifestations in 6 of them;
      3 patients suffered from euthyroid autoimmune thyroiditis from baseline, one
      after ipilimumab; 2 patients developed after transient thyrotoxicosis. Mean
      follow-up after anti-CTLA4 inhibitors treatment was 36 +/- 28 months. Thyroid
      disorders occurred 45.1 +/- 20.8 and 151 +/- 67 days after the initiation of
      CTLA4 and PD1 inhibitors, respectively. Autoimmune disorders and BRAF mutation
      were associated with a better clinical response to CTLA4 followed by PD1
      treatment. CONCLUSIONS: Immune checkpoint blockade is burdened by a high
      incidence of autoimmune thyroid dysfunction, which is often severe. Therefore,
      early and careful monitoring and, eventually, treatment are crucial to prevent
      the negative impact of thyroid dysfunction on the clinical outcome.

PMID- 29043577
TI  - Hepatic Hemolymphangioma Manifesting as Severe Anemia.

PMID- 29043576
TI  - Submucosal Tunneling Endoscopic Resection for the Treatment of Gastrointestinal
      Submucosal Tumors Originating from the Muscularis Propria Layer.
AB  - Surgical resection and endoscopic resection comprise two alternative options for
      the treatment of submucosal tumors (SMTs) originating from the muscularis propria
      (MP) layer. Endoscopic resection is minimally invasive compared with surgical
      resection. Conventional non-tunneling techniques, such as endoscopic submucosal
      dissection (ESD), endoscopic submucosal excavation (ESE), and endoscopic full
      thickness resection (EFR) have been demonstrated to be safe and effective.
      However, these techniques fail to maintain the integrity of the mucosa and induce
      high risk of perforation, infection, and postoperative strictures. Submucosal
      tunneling endoscopic resection (STER) is a novel surgical technique that can
      maintain the integrity of the mucosa by establishing a tunnel between the
      submucosal and the MP layers. STER has been proven to be effective and safe for
      the treatment of SMTs. Currently, STER has become a standard treatment for
      gastrointestinal (GI) SMTs originating from the MP layer, notably in China. In
      the present review, we describe the indications, procedures, postoperative care,
      efficacy and safety outcomes, and future perspectives of STER for GI SMTs
      originating from the MP layer.

PMID- 29043578
TI  - Duodenal Crohn's Disease-a Diagnostic Conundrum.
AB  - Gastroduodenal Crohn's disease is rare as most often the disease is found in the
      terminal ileum and colon rather than the upper gastrointestinal tract. The most
      common phenotype is stricturing disease which can lead to obstructive-like
      symptoms. Medical treatment options include proton pump inhibitors and biologic
      therapy. Endoscopic and surgical intervention may be needed to relieve the
      obstructive-like symptoms from the stricturing phenotype.

PMID- 29043579
TI  - Chylous Mesenteric Cyst.

PMID- 29043580
TI  - A Comprehensive Assessment of Accurate Lymph Node Staging and Preoperative
      Detection in Resected Pancreatic Cancer.
AB  - BACKGROUND: The current (seventh edition) American Joint Commission on Cancer
      (AJCC) Staging System for pancreatic ductal adenocarcinoma (PDAC) dichotomizes
      pathologic lymph node (LN) involvement into absence (pN0) or presence (pN1) of
      disease. The recently announced eighth edition also includes stratification on
      the number of positive nodes. Furthermore, LNs detected on preoperative imaging
      (CT, MRI, or endoscopic ultrasound-EUS) are considered to be pathologically
      involved in other gastrointestinal cancers. However, this is less well defined
      for PDAC. Therefore, the three aims of this study were to determine (1) whether
      the new AJCC staging system led to more accurate staging, (2) the number of nodes
      needed to be examined to detect pathologic involvement, and (3) if pN disease
      could be reliably detected on preoperative imaging in PDAC. METHODS: A
      retrospective review of all patients undergoing pancreatectomy at a single US
      academic center from January 1990 to September 2015. Pathology reports of
      resected specimens were reviewed to determine the total number of LNs examined
      and those positive for metastasis. CT, MRI, and/or EUS reports were used to
      determine the presence or absence of preoperatively detectable LN enlargement.
      RESULTS: Of the 490 surgical resections for PDAC, pN1 disease was detected in
      59.4% (n = 291) and was positively correlated with the number of LNs
      pathologically examined (P < 0.001). Patients with pN1 disease had a shorter
      overall survival (OS) than those without nodal involvement (25.1 vs. 44.0 months;
      P < 0.001); however, OS was not different when stratifying by the number of nodes
      as on the eighth AJCC system. Pathologic examination of > 20 LNs in treatment
      naive patients was optimal to detect pN1 disease and predict longer OS for those
      without nodal involvement (median survival > 41.1 months, P = 0.03 when compared
      to < 15 or 15-19 LNs examined). LNs were detected by CT, MRI, or EUS in 30.7%
      (103/335) of patients. The positive predictive value (PPV) of preoperative LN
      detection for pathologic involvement was 77.3% for treatment naive patients and
      84.2% for those without biliary obstruction. CONCLUSIONS: Although the LN scoring
      in the seventh PDAC AJCC Staging System was sufficient to predict OS of our
      patients, more LNs than previously considered (20 vs. 15) were optimal to detect
      pathologic involvement. Preoperative LN detection was an accurate predictor of
      pN1 disease for treatment naive patients without biliary obstruction.

PMID- 29043581
TI  - The Unique Blood Pressures and Pulsatility of LVAD Patients: Current Challenges
      and Future Opportunities.
AB  - An increasing number of end-stage heart failure patients are now implanted with
      continuous-flow left ventricular assist devices (CF-LVADs). Although this
      therapeutic approach is associated with improved clinical outcomes, continuous
      flow physiology reduces arterial pulse pressure and pulsatility to an extent that
      is unique to this population. Recent data suggest that high blood pressure (BP)
      contributes to life-threatening complications such as pump thrombosis and stroke
      of CF-LVAD patients. However, limited understanding of the distinct hemodynamics
      of these pumps makes measurement and, consequently, medical management of BP
      quite challenging. Here, we review the evolution of LVAD design, the impact of CF
      LVAD flow, and "artificial pulse" technology on hemodynamics and BP measurement,
      as well as suggest new approaches for the assessment and interpretation of the
      unique physiology of modern LVADs.

PMID- 29043583
TI  - Correction to: Delineation of the Role of Astroglial GABA Transporters in Seizure
      Control.
AB  - The original version of this article unfortunately contained a mistake. In Fig. 1
      two chemical structures are incorrect, namely exo-THPO and N-methyl-exo-THPO. The
      hydroxyl group (-OH) in the isoxazole ring is missing. The corrected Fig. 1 is
      given below.

PMID- 29043582
TI  - Triclosan-coated sutures and surgical site infection in abdominal surgery: the
      TRISTAN review, meta-analysis and trial sequential analysis.
AB  - INTRODUCTION: Surgical site infection (SSI) is a frequent complication of
      abdominal surgery causing increased morbidity. Triclosan-coated sutures are
      recommended to reduce SSI. The aim of this systematic review and meta-analysis
      was to evaluate the evidence from randomized controlled trials (RCT) comparing
      the rate of SSI in abdominal surgery when using triclosan-coated or uncoated
      sutures for fascial closure. METHODS: A systematic literature search was
      conducted using Medline, EMBASE, the Cochrane library, CINAHL, Scopus and Web of
      Science including publications until August 2017. The quality of the RCTs was
      evaluated using critical appraisal checklists from SIGN. Meta-analyses and trial
      sequential analysis were performed with Review Manager v5.3 and TSA software,
      respectively. RESULTS: Eight RCTs on abdominal wall closure were included in the
      meta-analysis. In an overall comparison including both triclosan-coated Vicryl
      and PDS sutures for fascial closure, triclosan-coated sutures were superior in
      reducing the rate of SSI (OR 0.67; 0.46-0.98). When evaluating PDS sutures
      separately, there was no effect of triclosan-coating on the rate of SSI (OR 0.85;
      0.61-1.17). Trial sequential analysis showed that the required information size
      (RIS) of 797 patients for triclosan-coated Vicryl sutures was almost reached with
      an accrued information size (AIS) of 795 patients. For triclosan-coated PDS
      sutures an AIS of 2707 patients was obtained, but the RIS was estimated to be
      18,693 patients. CONCLUSION: Triclosan-coated Vicryl sutures for abdominal
      fascial closure decrease the risk of SSI significantly and based on the trial
      sequential analysis further RCTs will not change that outcome. There was no
      effect on SSI rate with the use of triclosan-coated PDS sutures for abdominal
      fascial closure, and it is unknown whether additional RCTs will change that.

PMID- 29043584
TI  - Determination of the human cytochrome P450 monooxygenase catalyzing the
      enantioselective oxidation of 2,2',3,5',6-pentachlorobiphenyl (PCB 95) and
      2,2',3,4,4',5',6-heptachlorobiphenyl (PCB 183).
AB  - 2,2',3,5',6-Pentachlorobiphenyl (PCB 95) and 2,2',3,4,4',5',6-heptachlorobiphenyl
      (PCB 183) possess axial chirality and form the aS and aR enantiomers. The
      enantiomers of these congeners have been reported to accumulate in the human body
      enantioselectively via unknown mechanisms. In this study, we determined the
      cytochrome P450 (CYP) monooxygenase responsible for the enantioselective
      oxidization of PCB 95 and PCB 183, using a recombinant human CYP monooxygenase.
      We evaluated 13 CYP monooxygenases, namely CYP1A1, CYP1A2, CYP1B1, CYP2A6,
      CYP2B6, CYP2C8, CYP2C19, CYP2E1, CYP2J2, CYP3A4, CYP3A5, CYP4F2, and aromatase
      (CYP19), and revealed that CYP2A6 preferably oxidizes aS-PCB 95
      enantioselectively; however, it did not oxidize PCB 183. The enantiomer
      composition was elevated from 0.5 (racemate) to 0.54. In addition, following
      incubation with CYP2A6, the enantiomer fraction (EF) of PCB 95 demonstrated a
      time-dependent increase.

PMID- 29043585
TI  - Evaluation of leafy vegetables as bioindicators of gaseous mercury pollution in
      sewage-irrigated areas.
AB  - Mercury (Hg) can evaporate and enter the plants through the stomata of plant
      leaves, which will cause a serious threat to local food safety and human health.
      For the risk assessment, this study aimed to investigate the concentration and
      accumulation of total gaseous mercury (TGM) in five typical leafy vegetables
      (Chinese chives (Allium tuberosum Rottler), amaranth (Amaranthus mangostanus L.),
      rape (Brassica campestris L.), lettuce (Lactuca sativa L.), and spinach (Spinacia
      oleracea L.)) grown on sewage-irrigated areas in Tianjin, China. The following
      three sites were chosen to biomonitor Hg pollution: a paddy field receiving
      sewage irrigation (industrial and urban sewage effluents) for the last 30 years,
      a vegetable field receiving sewage irrigation for 15 years, and a grass field
      which did not receive sewage irrigation in history. Results showed that the total
      Hg levels in the paddy (0.65 mg kg-1) and vegetation fields (0.42 mg kg-1) were
      significantly higher than the local background level (0.073 mg kg-1) and the
      China national soil environment quality standard for Hg in grade I (0.30 mg kg
      1). The TGM levels in ambient air were significantly higher in the paddy (71.3 ng
      m-3) and vegetable fields (39.2 ng m-3) relative to the control (9.4 ng m-3) and
      previously reported levels (1.45 ng m-3), indicating severe Hg pollution in the
      atmospheric environment of the sewage-irrigated areas. Furthermore, gaseous
      mercury was the dominant form of Hg uptake in the leaves or irreversibly bound to
      leaves. The comparison of Hg uptake levels among the five vegetables showed that
      the gradient of Hg accumulation followed the order spinach > red amaranth >
      Chinese chives > rape > lettuce. These results suggest that gaseous Hg exposure
      in the sewage-irrigated areas is a dominant Hg uptake route in leafy vegetables
      and may pose a potential threat to agricultural food safety and human health.

PMID- 29043586
TI  - Photocatalytic decomposition of methanol over La/TiO2 materials.
AB  - Lanthanum-modified TiO2 photocatalysts (0.2-1.5 wt% La) were investigated in the
      methanol decomposition in an aqueous solution. The photocatalysts were prepared
      by the common sol-gel method followed by calcination. The structural (X-ray
      diffraction, Raman, X-ray photoelectron spectroscopy), textural (N2
      physisorption), and optical properties (diffuse reflectance spectroscopy,
      photoelectrochemical measurements) of all synthetized nanomaterials were
      correlated with photocatalytic activity. Both pure TiO2 and La-doped TiO2
      photocatalysts proved higher yields of hydrogen in comparison to photolysis. The
      photocatalyst with optimal amount of lanthanum (0.2 wt% La) showed almost two
      times higher amount of hydrogen produced at the same time as in the presence of
      pure TiO2. The photocatalytic activity increased with both increasing
      photocurrent response and decreasing amount of lattice and surface O species. It
      has been shown that both direct and indirect mechanisms of methanol
      photocatalytic oxidation participate in the production of hydrogen. Both direct
      and indirect mechanisms take part in the formation of hydrogen.

PMID- 29043587
TI  - Investigating the pros and cons of browns gas and varying EGR on combustion,
      performance, and emission characteristics of diesel engine.
AB  - The significance of mileage to the fruitful operation of a trucking organization
      cannot be downplayed. Fuel is one of the biggest variable expenses in a trucking
      wander. An attempt is made in this research to improve the combustion efficiency
      of a diesel engine for better fuel economy by introducing hydroxy gas which is
      also called browns gas or HHO gas in the suction line, without compromising
      performance and emission. Brown's gas facilitates the air-fuel mixture to ignite
      faster and efficient combustion. By considering safety and handling issues in
      automobiles, HHO gas generation by electrolysis of water in the presence of
      sodium bicarbonate electrolytes (NaHCO3) and usage was explored in this research
      work over compressed pure hydrogen, due to generation and capacity of immaculate
      hydrogen as of now confines the application in diesel engine operation. Brown's
      gas was utilized as a supplementary fuel in a single-cylinder, four-stroke
      compression ignition (CI) engine. Experiments were carried out on a constant
      speed engine at 1500 rpm, result shows at constant HHO flow rate of 0.73 liter
      per minute (LPM), brake specific fuel consumption (BSFC) decreases by 7% at idle
      load to 16% at full load, and increases brake thermal efficiency (BTE) by 8.9% at
      minimum load to 19.7% at full load. In the dual fuel (diesel +HHO) operation, CO
      emissions decreases by 19.4, 64.3, and 34.6% at 25, 50, and 75% load,
      respectively, and unburned hydrocarbon (UHC) emissions decreased by 11.3% at
      minimum load to 33.5% at maximum load at the expense of NOx emission increases by
      1.79% at 75% load and 1.76% at full load than neat diesel operation. The negative
      impact of an increase in NOx is reduced by adding EGR. It was evidenced in this
      experimental work that the use of Brown's gas with EGR in the dual fuel mode in a
      diesel engine improves the fuel efficiency, performance, and reduces the exhaust
      emissions.

PMID- 29043588
TI  - Determination of element composition and extraterrestrial material occurrence in
      moss and lichen samples from King George Island (Antarctica) using reactor
      neutron activation analysis and SEM microscopy.
AB  - Seven lichens (Usnea antarctica and U. aurantiacoatra) and nine moss samples
      (Sanionia uncinata) collected in King George Island were analyzed using
      instrumental neutron activation analysis, and concentration of major and trace
      elements was calculated. For some elements, the concentrations observed in moss
      samples were higher than corresponding values reported from other sites in the
      Antarctica, but in the lichens, these were in the same range of concentrations.
      Scanning electron microscopy (SEM) and statistical analysis showed large
      influence of volcanic-origin particles. Also, the interplanetary cosmic particles
      (ICP) were observed in investigated samples, as mosses and lichens are good
      collectors of ICP and micrometeorites.

PMID- 29043589
TI  - Assessment of filtration efficiency and physiological responses of selected plant
      species to indoor air pollutants (toluene and 2-ethylhexanol) under chamber
      conditions.
AB  - Three common plant species (Dieffenbachia maculata, Spathiphyllum wallisii, and
      Asparagus densiflorus) were tested against their capacity to remove the air
      pollutants toluene (20.0 mg m-3) and 2-ethylhexanol (14.6 mg m-3) under light or
      under dark in chamber experiments of 48-h duration. Results revealed only limited
      pollutant filtration capabilities and indicate that aerial plant parts of the
      tested species are only of limited value for indoor air quality improvement. The
      removal rate constant ranged for toluene from 3.4 to 5.7 L h-1 m-2 leaf area with
      no significant differences between plant species or light conditions
      (light/dark). The values for 2-ethylhexanol were somewhat lower, fluctuating
      around 2 L h-1 m-2 leaf area for all plant species tested, whereas differences
      between light and dark were observed for two of the three species. In addition to
      pollutant removal, CO2 fixation/respiration and transpiration as well as quantum
      yield were evaluated. These physiological characteristics seem to have no major
      impact on the VOC removal rate constant. Exposure to toluene or 2-ethylhexanol
      revealed no or only minor effects on D. maculata and S. wallisii. In contrast, a
      decrease in quantum yield and CO2 fixation was observed for A. densiflorus when
      exposed to 2-ethylhexanol or toluene under light, indicating phytotoxic effects
      in this species.

PMID- 29043590
TI  - Adsorption and desorption for dynamics transport of hexavalent chromium (Cr(VI))
      in soil column.
AB  - Batch experiments have been carried out to study the adsorption of heavy metals
      in soils, and the migration and transformation of hexavalent chromium (Cr(VI)) in
      the soil of a vegetable base were studied by dynamic adsorption and desorption
      soil column experiments. The aim of this study was to investigate the effect of
      initial concentration and pH value on the adsorption process of Cr(VI).
      Breakthrough curve were used to evaluate the capacity of Cr(VI) adsorption in
      soil columns. The results show that the higher the initial concentration, the
      worse the adsorption capacity of Cr(VI). The adsorption of Cr(VI) was strongly
      sensitive to pH value. The capacity of Cr(VI) adsorption is maximized at very low
      pH value. This may be due to changes in pH that cause a series of complex
      reactions in Cr(VI). In a strongly acidic environment, the reaction of Cr(VI)
      with hydrogen ions is accompanied by the formation of Cr3+, which reacts with the
      soil free iron-aluminum oxide to produce hydroxide in the soil. The results of
      the desorption experiments indicate that Cr(VI) is more likely to leach from this
      soil, but if the eluent is a strong acid solution, the leaching process will be
      slow and persistent. During the experiment, the pH value of the effluent was in
      the range of 7-8.5, which tends to the original pH value of the soil. It is
      indicating that the soil has a strong buffer on the acid liquid. The program
      CXTFIT was used to fit the breakthrough curve to estimate parameters. The results
      of the calculation of the dispersion coefficient (D) can be obtained by this
      program. The two-site model fit the breakthrough curve data of Cr(VI) well, and
      the parameters calculated by the CXTFIT can be used to explain the behavior of
      Cr(VI) migration and transformation in soil columns. When pH = 2, the retardation
      factor (R) reach at 79.71 while the value of the R is generally around 10 in
      other experiments. The partitioning coefficient beta shows that more than half of
      the adsorption sites are instantaneous in this adsorption process and non
      equilibrium affects the Cr(VI) transport process in this soil.

PMID- 29043591
TI  - Alternaria alternata (Fr.) Keissl with mutation G143A in the Cyt b gene is the
      source of a difficult-to-control allergen.
AB  - The saprotrophic fungus Alternaria alternata is widespread in the agro
      environment and produces more than ten allergenic proteins, mostly protein Alt a
      1. The frequency of the Alt a 1 gene was analyzed in a group of A. alternata
      isolates from winter wheat kernels obtained in Poland, and the effectiveness of
      various fungicides targeting the pathogen was evaluated. The Alt a 1 gene was
      identified in four of the seven tested isolates. A. alternata colonized 35.67%
      kernels on average, but its frequency increased in stored grain where the
      presence of epiphytes was noted on 23.09 to 51.38% kernels, and endophytes-in
      26.21 to 42.01% of kernels. The efficacy of field-applied fungicides did not
      exceed 50%, despite the fact that A. alternata is highly sensitive to
      propiconazole, fenpropimorph, and tebuconazole under in vitro conditions. The
      analyzed isolates were characterized by limited sensitivity to azoxystrobin (EC50
      ranged from 0.505 to 1.350 MUg cm-3) due to a mutation at codon 143 of the CYT b
      gene, responsible for resistance to quinone outside inhibitor fungicides, which
      was noted in all isolates. The spread of A. alternata can be effectively
      controlled with suitable fungicides and by monitoring the prevalence of
      pathogenic isolates in the environment.

PMID- 29043592
TI  - Factors Associated with Surveillance Adenoma and Sessile Serrated Polyp Detection
      Rates.
AB  - BACKGROUND: Adenoma detection rate (ADR) and sessile serrated polyp detection
      rate (SSPDR) data in surveillance colonoscopy are limited. AIMS: Our aim was to
      determine surveillance ADR and SSPDR and identify associated predictors. METHODS:
      A retrospective review of subjects who underwent surveillance colonoscopy for
      adenoma and/or SSP at an academic center was performed. The following exclusion
      criteria were applied: prior colonoscopy <= 3 years, incomplete examination, or
      another indication for colonoscopy. Patient, endoscopist, and procedure
      characteristics were collected. Predictors were identified using multivariable
      logistic regression. RESULTS: Of 3807 colonoscopies, 2416 met inclusion criteria.
      Surveillance ADR was 49% and, SSPDR was 8%. Higher ADR was associated with: age
      per year (OR 1.03; 95% CI 1.02-1.04), male gender (OR 1.55; 95% CI 1.29-1.88),
      BMI per kg/m2 (OR 1.02; 95% CI 1.01-1.04), withdrawal time per minute (OR 1.09;
      95% CI 1.07-1.10), and endoscopists' screening ADR (OR 1.01; 95% CI 1.00-1.03).
      Years since training (OR 0.99; 95% CI 0.98-0.99) was associated with lower ADR.
      Family history of CRC (OR 1.58; 95% CI 1.02-2.27) and endoscopists' screening ADR
      (OR 1.40; 95% CI 1.15-1.74) were associated with higher SSPDR. African-American
      race (OR 0.36; 95% CI 0.10-0.75) and diabetes (OR 0.41; 95% CI 0.21-0.76) were
      associated with lower SSPDR. CONCLUSIONS: For surveillance colonoscopy, nearly
      half of patients had an adenoma and one in twelve had an SSP. In addition to
      established factors, BMI, endoscopists' screening ADR, and years since training
      were associated with ADR, whereas African-American race and diabetes were
      inversely associated with SSPDR. Further studies are needed prior to integrating
      surveillance ADR and SSPDR into quality metrics.

PMID- 29043593
TI  - Fecal Calprotectin in Monitoring the Disease Activity in Colonic Inflammatory
      Bowel Disease.

PMID- 29043594
TI  - Specialty Care Access Network-Extension of Community Healthcare Outcomes Model
      Program for Liver Disease Improves Specialty Care Access.
AB  - BACKGROUND AND AIMS: To improve subspecialty access, VA Ann Arbor Healthcare
      System (VAAAHS) implemented the first Specialty Care Access Network (SCAN)
      Extension of Community Healthcare Outcomes (ECHO) in chronic liver disease. SCAN
      ECHO Liver links primary care providers (PCPs) to hepatologists via secure video
      teleconferencing. We aim to describe characteristics of participants (PCPs) and
      patients (clinical question and diagnosis) in SCAN-ECHO Liver. METHODS: This is a
      prospective study of the VAAAHS SCAN-ECHO Liver (June 10, 2011-March 31, 2015).
      This evaluation was carried out as a non-research activity under the guidance
      furnished by VHA Handbook 1058.05. It was approved through the Medicine Service
      at VAAAHS as noted in the attestation document which serves as documentation of
      approved non-research, quality improvement activities in VHA. RESULTS: In total,
      106 PCPs from 23 sites participated. A total of 155 SCAN-ECHO sessions discussed
      519 new and 49 return patients. 29.4% of Liver Clinic requests were completed in
      SCAN-ECHO Liver. SCAN-ECHO Liver consults were completed an average of 10 days
      sooner than in conventional clinic. Potential travel saving was 250 miles round
      trip (median 255 (IQR 142-316) per patient. CONCLUSION: SCAN-ECHO Liver provided
      specialty care with increased efficiency and convenience for chronic liver
      disease patients. One of three of Liver Clinic consults was diverted to SCAN-ECHO
      Liver, reducing consult completion time by 20%.

PMID- 29043595
TI  - Stress Hormone Cortisol Enhances Bcl2 Like-12 Expression to Inhibit p53 in
      Hepatocellular Carcinoma Cells.
AB  - BACKGROUND AND AIMS: The pathogenesis of hepatocellular carcinoma (HC) is
      unclear. It is suggested that psychological stress associates with the
      pathogenesis of liver cancer. Bcl2-like protein 12 (Bcl2L12) suppresses p53
      protein. This study tests a hypothesis that the major stress hormone, cortisol,
      inhibits the expression of p53 in HC cells (HCC) via up regulating the expression
      of Bcl2L12. METHODS: Peripheral blood samples were collected from patients with
      HC to be analyzed for the levels of cortisol. HCC were cultured to assess the
      role of cortisol in the regulation of the expression of Bcl2L12 and p53 in HCC.
      RESULTS: We observed that the serum cortisol levels were higher in HC patients.
      Expression of Bcl2L12 in HCC was correlated with serum cortisol. Cortisol
      enhanced the Bcl2L12 expression in HCC. Bcl2L12 binding to the TP53 promoter was
      correlated with p53 expression in HCC. Cortisol increased the Bcl2L12 expression
      in HCC to inhibit p53 expression. CONCLUSIONS: Stress hormone cortisol suppresses
      p53 in HCC via enhancing Bcl2L12 expression in HCC. The results suggest that
      cortisol may be a therapeutic target for the treatment of HC.

PMID- 29043596
TI  - Short-term Prospective Questionnaire Study of Early Postoperative Quality of Life
      After Colorectal Endoscopic Submucosal Dissection.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) has become popular as an
      alternative to laparoscopy-assisted colectomy (LAC) for early colorectal cancer.
      AIM: To validate postoperative quality of life (QOL) based on subjective symptoms
      of patients from questionnaire survey. METHODS: We prospectively enrolled
      patients planned to undergo ESD for adenoma or Tis/T1a cancer at our institution
      between December 2011 and January 2013. Controls were prospectively enrolled LAC
      patients diagnosed with T1b cancer. Patients answered questionnaire survey on QOL
      on postoperative day (POD) 1 and POD14. Questions were scored using visual analog
      scale (0 points = worst condition, 100 points = best condition) and were
      classified into six categories: health status, mental status (MeS), motor status
      (MoS), bodily painless, passage and anorectal function (PAF), and stress for the
      treatment. Total score was also calculated. We compared the median scores among
      categories using the Wilcoxon rank-sum test. RESULTS: A total of 82 ESDs and 41
      LACs were included. Median score for the factors in questionnaire (POD1/POD14) in
      ESDs versus LACs for colonic lesion (rectal lesion) was as follows: MeS, 74/83
      versus 54/73 (72/85 vs. 42/62); MoS, 98/96 versus 51/75 (95/90 vs. 66/67); PAF,
      90/96 versus 80/80 (90/95 vs. 70/53); total score, 83/91 versus 58/75 (81/87 vs.
      51/66). These items showed statistical significant differences between ESDs and
      LACs. CONCLUSIONS: Postoperative QOL and symptoms are significantly better on
      POD1 and POD14 following ESD compared with LAC.

PMID- 29043597
TI  - Do holocentric chromosomes represent an evolutionary advantage? A study of paired
      analyses of diversification rates of lineages with holocentric chromosomes and
      their monocentric closest relatives.
AB  - Despite most of the cytogenetic research is focused on monocentric chromosomes,
      chromosomes with kinetochoric activity localized in a single centromere, several
      studies have been centered on holocentric chromosomes which have diffuse
      kinetochoric activity along the chromosomes. The eukaryotic organisms that
      present this type of chromosomes have been relatively understudied despite they
      constitute rather diversified species lineages. On the one hand, holocentric
      chromosomes may present intrinsic benefits (chromosome mutations such as fissions
      and fusions are potentially neutral in holocentrics). On the other hand, they
      present restrictions to the spatial separation of the functions of recombination
      and segregation during meiotic divisions (functions that may interfere),
      separation that is found in monocentric chromosomes. In this study, we compare
      the diversification rates of all known holocentric lineages in animals and plants
      with their most related monocentric lineages in order to elucidate whether
      holocentric chromosomes constitute an evolutionary advantage in terms of
      diversification and species richness. The results showed that null hypothesis of
      equal mean diversification rates cannot be rejected, leading us to surmise that
      shifts in diversification rates between holocentric and monocentric lineages
      might be due to other factors, such as the idiosyncrasy of each lineage or the
      interplay of evolutionary selections with the benefits of having either
      monocentric or holocentric chromosomes.

PMID- 29043598
TI  - Anti-human immunodeficiency virus-1 activities of pratensein and pratensein
      glycoside from Alhaji maurorum and its parasite Cuscuta kotchiana.
AB  - OBJECTIVE: To test the anti-human immunodeficiency virus (HIV) activity of pure
      compounds isolated from aerial part extracts of Alhaji maurorum and its parasite
      Cuscuta kotchiana. METHODS: The anti-HIV-1 and anti-HIV-2 activities of these
      extracts were performed by use of quantitative polymerase chain reaction assay
      and high pure viral nucleic acid kit. The most active fractions against HIV-1
      were detected by nuclear magnetic resonance as pratensein and pratensein
      glycoside respectively in A. maurorum and C. campestris. RESULTS: These two
      extracts have low toxicity on HIV-2 replication. The 50% effective concentration
      for HIV-1 replication of pratensein and pratensein glycoside were 100 and 22
      MUg/mL, respectively. The time of addition assay showed that pratensein and
      pratensein glycoside were most effective when added at the early stage (0-4 h) of
      virus replication. CONCLUSION: The pratensein glycoside inhibits HIV-1
      replication in host cells more than pratensein and both extracts are potent
      inhibitors of HIV-1 entry.

PMID- 29043599
TI  - Shenyi Capsule () plus Chemotherapy versus Chemotherapy for Non-Small Cell Lung
      Cancer: A Systematic Review of Overlapping Meta-Analyses.
AB  - OBJECTIVE: To assist decision-makers interpret and choose among conflfl icting
      meta-analyses, as well as to offer treatment recommendations based on current
      best evidence by performing a systematic review of overlapping meta-analyses
      regarding Shenyi Capsule (, SC) plus chemotherapy versus chemotherapy of non
      small cell lung cancer (NSCLC). METHODS: A literature search was conducted to
      select systematic reviews comparing SC plus chemotherapy with chemotherapy for
      NSCLC. Meta-analyses only composed of randomized controlled trials (RCTs) met the
      inclusion criteria. Two authors individually estimated the quality of meta
      analysis and extracted data. The Jadad decision algorithm was applied to
      guarantee which meta-analysis provided the best original evidence. RESULTS: A
      total of 5 meta-analyses were included. All the studies composed of RCTs or quasi
      RCTs and were regarded as level-II evidence. The scores of the Assessment of
      Multiple Systematic Reviews ranged from 3 to 6 (median 4). A high-quality meta
      analysis with more RCTs was chosen, which suggested that SC plus chemotherapy
      could increase incidence of short-term efficacy, improve the quality of life and
      survival rate in comparison to chemotherapy. However, there was no statistically
      significant difference between SC plus chemotherapy and chemotherapy regarding
      chemotherapy-induced side effect, such as liver and kidney function obstacle,
      leukopenia, hemoglobin decrement and gastrointestinal adverse reaction.
      CONCLUSIONS: Based on the best available evidence, treatment effect of SC plus
      chemotherapy was better than chemotherapy and did not increase side effects.
      Therefore, SC plus chemotherapy may be superior to chemotherapy for treating
      NSCLC. However, due to some limitations, SC plus chemotherapy should be
      cautiously considered, and further high-quality meta-analyses are needed.

PMID- 29043600
TI  - Effects of ultrasound-guided stellate-ganglion block on sleep and regional
      cerebral oxygen saturation in patients undergoing breast cancer surgery: a
      randomized, controlled, double-blinded trial.
AB  - Numerous factors could contribute to sleep disturbances in women with breast
      cancer. We hypothesized that stellate ganglion block (SGB) during surgery would
      preserve sleep after surgery and increase intraoperative regional cerebral oxygen
      saturation (rSO2) on the blocked side in patients undergoing breast cancer
      surgery. A randomized, double-blinded, controlled trial was conducted at the
      First Hospital of China Medical University from January 2016 to September 2016.
      Ninety-six patients who underwent radical breast cancer surgery requiring general
      anaesthesia were randomly assigned to one of two study groups: a control group
      that received a saline SGB and a block group that received a 0.25% ropivacaine
      hydrochloride SGB. The primary outcome measure was the postoperative sleep
      profile, which was assessed using the bispectral index on the first postoperative
      night. The secondary outcome measure was the intraoperative rSO2, monitored was
      throughout surgery using near-infrared spectroscopy. A total of 91 female
      patients (mean age: 45 years; range 24-51 years) were included in the study. The
      duration of sleep was significantly increased by 66.3 min in the ropivacaine-SGB
      group compared with the saline-SGB group. No differences in rSO2 were observed on
      either the left or right side of the patients in either group 50 min after
      anaesthesia induction. We conclude that ropivacaine-SGB combined with general
      anaesthesia might increase the first postoperative sleep duration without
      influencing the intraoperative rSO2 in female patients undergoing elective breast
      cancer surgery. Clinical trials.gov identifier NCT02651519.

PMID- 29043602
TI  - Fluorinated pyrrole incorporated 2-thiazolyl hydrazone motifs: a new class of
      antimicrobial and anti tuberculosis agents.
AB  - In aim of obtaining novel bio-active compounds, a new series of fluorinated 1-(4
      (aryl)thiazol-2-yl)-2-((1-(aryl)-2,5-dimethyl-1H-pyrrol-3-yl)methylene)hydrazines
      (5a-t) and 1-(4-(4-aryl)thiazol-2-yl)-2-((3-(2,4-dichlorophenyl)-1-phenyl-1H
      pyrazol-4-yl)methylene)hydrazines (8a-d) were synthesized and screened for their
      antibacterial and antifungal activities. The potent compounds were further
      screened in vitro for anti-tuberculosis activity against Mycobacterium
      tuberculosis H37Rv strain. Compounds 5a, 5c-5h and 5m were found to be good
      inhibitors of B. subtilis with MIC ranging from 0.2 to 0.8 ug mL-1, which are
      nearly three to ten times more potent than the standard drug Ciprofloxacin.
      Compounds 5a, 5h-5k and 5o exhibited potent antifungal activity against C.
      albicans strain with MIC ranging from 0.4 to 1.6 ug mL-1. Compounds 8a-8c were
      found to be excellent inhibitors of A. niger. Compounds 5a and 5k showed
      significant anti tubercular activity with MIC 3.12 and 6.25 ug mL-1 respectively.
      Furthermore, highly active compounds were tested for their preliminary toxicity
      profile by hemolytic assay and were found to be non hemolytic at higher
      concentration with good selectivity index. Cytotoxicity of the potent compounds
      5a, 5d, 5g, 5i and 5k was checked by MTT assay using normal embryonic kidney cell
      line HEK 293 and found to be non-toxic up to 50-200 times the MIC for
      antibacterial activity.

PMID- 29043601
TI  - Pupillary reflex dilation in response to incremental nociceptive stimuli in
      patients receiving intravenous ketamine.
AB  - Pupillometry is a non-invasive monitoring technique, which allows dynamic
      pupillary diameter measurement by an infrared camera. Pupillary diameter
      increases in response to nociceptive stimuli. In patients anesthetized with
      propofol or volatile agents, the magnitude of this pupillary dilation is related
      to the intensity of the stimulus. Pupillary response to nociceptive stimuli has
      never been studied under ketamine anesthesia. Our objective was to describe
      pupillary reflex dilation after calibrated tetanic stimulations in patients
      receiving intravenous ketamine. After written consent, 24 patients of our
      pediatric burn care unit were included. They received an oral morphine
      premedication (0.3 mg kg-1) 1 h before their scheduled daily dressing change.
      Just before the procedure, they received 1 mg kg-1 of intravenous ketamine. Two
      minutes after this bolus, tetanic stimulations of incremental intensities were
      performed on the arm of each patient (5-10-20-30-40-60 mA, 60 s interval between
      stimulations). Pupillary diameter, heart rate and movements were recorded before
      and after each stimulation. Tetanic stimulations were associated with changes in
      pupillary diameter and heart rate. The magnitude of these changes was
      significantly influenced by the intensity of stimulation (ANOVA for repeated
      measures, p < 0.001). Movement was associated with a 32% increase in diameter
      (ROC curves, AUC 0.758) with 65% sensitivity and 77% specificity. In children,
      pupillary reflex dilation to nociceptive stimuli persists under deep sedation
      obtained with 1 mg kg-1 of intravenous ketamine combined with a 0.3 mg kg-1 oral
      morphine premedication, and its magnitude depends on the intensity of the
      stimulation. Our results confirm that pupillometry could be a relevant way to
      monitor nociception in anaesthetised subjects, including those receiving
      ketamine. Trial registration clinicaltrials.gov, NCT 02648412.

PMID- 29043603
TI  - Epigenetic modifications of gene expression by lifestyle and environment.
AB  - Epigenetics oftenly described as the heritable changes in gene expression
      independent of changes in DNA sequence. Various environmental factors such as
      nutrition-dietary components, lifestyle, exercise, physical activity, toxins, and
      other contributing factors remodel the genome either in a constructive or
      detrimental way. Since epigenetic changes are reversible and nutrition is one of
      the many epigenetic regulators that modify gene expression without changing the
      DNA sequence, dietary nutrients and bioactive food components contribute to
      epigenetic phenomena either by directly suppressing DNA methylation or histone
      catalyzing enzymes or by changing the availability of substrates required for
      enzymatic reactions. Diets that contain catechol-dominant polyphenols are
      reported to suppress enzyme activity and activate epigenetically silenced genes.
      Furthermore, several dietary nutrients play a crucial role in one-carbon
      metabolism including folate, cobalamin, riboflavin, pyridoxine, and methionine by
      directly affecting S-adenosyl-L-methionine. Soy polyphenols block DNA
      methyltransferases and histone deacetylases to reverse aberrant CpG island
      methylation. Organosulfur rich compounds such as the sulforaphane found in
      broccoli appear to normalize DNA methylation and activate miR-140 expression,
      which represses SOX9 and ALDH1 and decreases tumor growth. The purpose of this
      short communication is to overview the epigenetic regulatory mechanisms of diet
      and other environmental factors. We discuss the epigenetic contributions of
      dietary components with a particular focus on nutritional polyphenols and
      flavonoids as epigenetic mediators that modify epigenetic tags and control gene
      expression. These mechanisms provide new insights to better understand the
      influence of dietary nutrients on epigenetic modifications and gene expression.

PMID- 29043604
TI  - First Steps towards the Pharmaceutical Development of Ovules Containing
      Lactobacillus Strains: Viability and Antimicrobial Activity as Basic First
      Parameters in Vaginal Formulations.
AB  - In the majority of Latin-American countries, including Argentina, there is a
      limited availability of vaginal bioproducts containing probiotics in the market.
      In addition, the conventional treatments of genital tract infections in women
      represent a high cost to the public health systems. The future development of
      this type of bioproducts that employ specific lactobacilli strains would not only
      have a meaningful impact on women's health but would also represent a significant
      challenge to the pharmaceutical industry. The aims of the work described in this
      paper were (i) to study different pharmaceutical formulations of vaginal ovules
      containing Lactobacillus fermentum L23 and L. rhamnosus L60, to determine in
      which formulation lactobacilli viability was sustained for longer time and (ii)
      to evaluate if probiotic strains maintained both the antimicrobial activity and
      biofilm-producing ability after being recovered from the ovules. In this study,
      we developed and characterized three pharmaceutical formulations containing
      different glycerol amounts and specific lactobacilli strains. Three relevant
      parameters, cell viability, antimicrobial activity, and biofilm production, by
      lactobacilli recovered from the ovules were tested. Although the viability of L23
      and L60 strains was mainly influenced by high ovule's glycerol proportion, they
      survived at 4  degrees C during the 180 days. Both lactobacilli's antimicrobial
      activity and biofilm-producing ability were maintained for all treatments. In
      conclusion, employing a much reduced number of components, we were able to select
      the most suitable pharmaceutical formulation which maintained not only
      lactobacilli viability for a long period of time but also their antimicrobial
      activity and biofilm-producing ability.

PMID- 29043605
TI  - Liquid Nanosize Emulsion-Filled Enteric-Coated Capsules for Colon Delivery of
      Immunosuppressant Peptide.
AB  - Present study aims at solubilizing slightly water-soluble peptide into a nanosize
      emulsion which is filled into a hard gelatin capsule in the form of
      preconcentrate. Further, liquid-filled capsule was dip-coated with ethyl
      cellulose and Eudragit S100 for colon targeting. An in vitro release profile was
      studied for selected formulations, i.e., Formulation A (5 mg ethyl cellulose and
      40 mg Eudragit S100), Formulation B (10 mg ethyl cellulose and 30 mg Eudragit
      S100), and Formulation C (10 mg ethyl cellulose and 20 mg Eudragit S100).
      Formulations B and A showed an immediate release after 5 and 6 h, respectively,
      which represents ileo-ceacal transit time. The nanosize of emulsion, i.e., below
      100 nm, was confirmed by transmission electron microscopy. Also, a phase
      transition of nanosize emulsion from water in oil to oil in water on dilution
      with water was observed through TEM. This novel approach of filling poorly water
      soluble protein in solubilized form of nanosize emulsion preconcentrate into
      coated hard gelatin capsules for colon targeting has been reported first time.
      This approach could be a breakthrough for the better management of local
      intestinal pathologies.

PMID- 29043606
TI  - Optimizing echo guidance during MitraClip using fluoroscopy: how to see better!

PMID- 29043607
TI  - DDR2 and IFITM1 Are Prognostic Markers in Gallbladder Squamous Cell/Adenosquamous
      Carcinomas and Adenocarcinomas.
AB  - This study was conducted to investigate the expressions of DDR2 and IFITM1 and
      their clinical and pathological significances in the rare type squamous
      cell/adenosquamous carcinomas (SC/ASC) and ordinary adenocarcinomas (AC) of
      gallbladder cancers. DDR2 and IFITM1 expression was examined in 69 SC/ASCs and
      146 ACs using EnVision immunohistochemistry. Results showed that the percentage
      of positive DDR2 and IFITM1 expression was significantly higher in SC/ASC
      patients with high TNM stage, lymph node metastasis, invasion, and no resection
      surgery compared to patients with low TNM stages, no lymph node metastasis, no
      invasion, and resection surgery (P < 0.05 or P < 0.01). The positive rate of DDR2
      was significantly higher in SC/ASC patients with large tumor sizes than patients
      with small tumor sizes (p < 0.05). The percentage of positive DDR2 and IFITM1
      expressions was significantly higher in AC patients with high TNM stages that
      didn't receive resection surgery compared to patients with low TNM stages that
      did receive resection surgery (P < 0.05 or P < 0.01). The positive rate of IFITM1
      was significantly higher in AC patients with lymph node metastasis and invasion
      than in patients without metastasis and invasion (p < 0.05). Positive DDR2 and
      IFITM1 expression was closely associated with a decreased overall survival in
      SC/ASC and AC patients (P < 0.05 or P < 0.01). AUC analysis showed that DDR2 and
      IFITM1 was sensitive and specific for the diagnosis of SC/ASC (AUC = 0.740 and
      AUC =0.733, respectively) and AC (AUC = 0.710 and AUC =0.741, respectively). In
      conclusion, positive DDR2 and IFITM1 expression is a marker for the clinical
      severity, poor prognosis, and diagnosis of gallbladder SC/ASC and AC.

PMID- 29043608
TI  - Limitations of high throughput methods for miRNA expression profiles in non
      functioning pituitary adenomas.
AB  - Microarray, RT-qPCR based arrays and next-generation-sequencing (NGS) are
      available high-throughput methods for miRNA profiling (miRNome). Analytical and
      biological performance of these methods were tested in identification of
      biologically relevant miRNAs in non-functioning pituitary adenomas (NFPA).
      miRNome of 4 normal pituitary (NP) and 8 NFPA samples was determined by these
      platforms and expression of 21 individual miRNAs was measured on 30 (20 NFPA and
      10 NP) independent samples. Complex bioinformatics was used. 132 and 137 miRNAs
      were detected by all three platforms in NP and NFPA, respectively, of which 25
      were differentially expressed (fold change > 2). The strongest correlation was
      observed between microarray and TaqMan-array, while the data obtained by NGS were
      the most discordant despite of various bioinformatics settings. As a technical
      validation we measured the expression of 21 selected miRNAs by individual RT-qPCR
      and we were able to validate 35.1%, 76.2% and 71.4% of the miRNAs revealed by
      SOLiD, TLDA and microarray result, respectively. We performed biological
      validation using an extended number of samples (20 NFPAs and 8 NPs). Technical
      and biological validation showed high correlation (p < 0.001; R = 0.96). Pathway
      and network analysis revealed several common pathways but no pathway showed the
      same activation score. Using the 25 platform-independent miRNAs developmental
      pathways were the top functional categories relevant for NFPA genesis. The
      difference among high-throughput platforms is of great importance and selection
      of screening method can influence experimental results. Validation by another
      platform is essential in order to avoid or to minimalize the platform specific
      errors.

PMID- 29043610
TI  - Transient focal neurologic deficits upon hematopoietic stem cell transplantation:
      just a coincidence?

PMID- 29043609
TI  - The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection.
AB  - PURPOSE OF REVIEW: The aim of this review is to summarize knowledge of the
      prevalence, relevant physiology, and consequences of obesity and visceral
      adiposity in HIV-infected adults, including highlighting gaps in current
      knowledge and future research directions. RECENT FINDINGS: Similar to the general
      population, obesity prevalence is increasing among HIV-infected persons, and
      obesity and visceral adiposity are associated with numerous metabolic and
      inflammatory sequelae. However, HIV- and antiretroviral therapy (ART)-specific
      factors may contribute to fat gain and fat quality in treated HIV infection,
      particularly to the development of visceral adiposity, and sex differences may
      exist. Obesity and visceral adiposity commonly occur in HIV-infected persons and
      have significant implications for morbidity and mortality. Future research should
      aim to better elucidate the HIV- and ART-specific contributors to obesity and
      visceral adiposity in treated HIV infection, with the goal of developing targeted
      therapies for the prevention and treatment of obesity and visceral adiposity in
      the modern ART era.

PMID- 29043611
TI  - Quantifying anthropogenic threats to orchids using the IUCN Red List.
AB  - Orchids are diverse, occur in a wide range of habitats and dominate threatened
      species lists, but which orchids are threatened, where and by what? Using the
      International Union for Conservation of Nature Red List, we assessed the range
      and diversity of threats to orchids globally including identifying four threat
      syndromes: (1) terrestrial orchids in forests that are endemic to a country and
      threatened by illegal collecting; (2) orchids threatened by climate change,
      pollution, transportation and disturbance/development for tourism, and recreation
      activities, often in East Asia; (3) epiphytic orchids in Sub-Saharan Africa
      including Madagascar with diverse threats; and (4) South and Southeast Asia
      orchids threatened by land clearing for shifting agriculture. Despite limitations
      in the Red List data, the results highlight how conservation efforts can focus on
      clusters of co-occurring threats in regions while remaining aware of the trifecta
      of broad threats from plant collecting, land clearing and climate change.

PMID- 29043612
TI  - The A-Like Faker Assay for Measuring Yeast Chromosome III Stability.
AB  - The ability to rapidly assess chromosome instability (CIN) has enabled profiling
      of most yeast genes for potential effects on genome stability. The A-like faker
      (ALF) assay is one of several qualitative and quantitative marker loss assays
      that indirectly measure loss or conversion of genetic material using a
      counterselection step. The ALF assay relies on the ability to count spurious
      mating events that occur upon loss of the MATalpha locus of haploid Saccharomyces
      cerevisiae strains. Here, we describe the deployment of the ALF assay for both
      rapid and simple qualitative, and more in-depth quantitative analysis allowing
      determination of absolute ALF frequencies.

PMID- 29043613
TI  - The Chromosome Transmission Fidelity Assay for Measuring Chromosome Loss in
      Yeast.
AB  - The budding yeast Saccharomyces cerevisiae has served as an excellent model
      system for studying highly conserved biological pathways including pathways
      involved in genome transmission and maintenance. The Chromosome Transmission
      Fidelity (CTF) colony color assay was developed to assess chromosome instability
      (CIN) in yeast, by monitoring the loss or gain during cell division of an
      artificial chromosome fragment carrying a visual marker. The CTF assay monitors
      changes in chromosome number, allowing the detection of mutants that exhibit
      increased rates of chromosome nondisjunction or chromosome loss. In this article,
      we describe the SUP11-marker-based CTF assay system, and the methodologies for
      both qualitative analysis of mutants affecting chromosome transmission, and
      quantitative analysis for determining the types and rates of errors in chromosome
      transmission using half-sector analysis.

PMID- 29043614
TI  - Measuring Mutation Rates Using the Luria-Delbruck Fluctuation Assay.
AB  - The Luria-Delbruck fluctuation assay is one of the most commonly used methods for
      measuring the mutation rate in microorganisms. Specifically, it is used to
      measure the mutation rate at a particular locus or loci at which mutations give
      rise to a selectable phenotype. Here, I outline the essential features of
      performing Luria-Delbruck fluctuation assays as well as common missteps and tips
      for improving the accuracy of mutation rate estimates. In addition, I provide
      tools for analyzing data from fluctuation assays. This 96-well plate protocol has
      been optimized for use in yeast but should perform equally well for a range of
      microorganisms using standard microbiological methods.

PMID- 29043615
TI  - Molecular Genetic Characterization of Mutagenesis Using a Highly Sensitive Single
      Stranded DNA Reporter System in Budding Yeast.
AB  - Mutations are permanent alterations to the coding content of DNA. They are
      starting material for the Darwinian evolution of species by natural selection,
      which has yielded an amazing diversity of life on Earth. Mutations can also be
      the fundamental basis of serious human maladies, most notably cancers. In this
      chapter, I describe a highly sensitive reporter system for the molecular genetic
      analysis of mutagenesis, featuring controlled generation of long stretches of
      single-stranded DNA in budding yeast cells. This system is ~100- to ~1000-fold
      more susceptible to mutation than conventional double-stranded DNA reporters, and
      is well suited for generating large mutational datasets to investigate the
      properties of mutagens.

PMID- 29043616
TI  - Analyzing Genome Rearrangements in Saccharomyces cerevisiae.
AB  - Genome rearrangements underlie different human diseases including many cancers.
      Determining the rates at which genome rearrangements arise and isolating unique,
      independent genome rearrangements is critical to understanding the genes and
      pathways that prevent or promote genome rearrangements. Here, we describe
      quantitative S. cerevisiae genetic assays for measuring the rates of accumulating
      genome rearrangements including deletions, translocations, and broken chromosomes
      healed by de novo telomere addition that result in the deletion of two counter
      selectable genes, CAN1 and URA3, placed in the nonessential regions of the S.
      cerevisiae genome. The assays also allow for the isolation of individual genome
      rearrangements for structural studies, and a method for analyzing genome
      rearrangements by next-generation DNA sequencing is provided.

PMID- 29043617
TI  - High-Resolution Mapping of Modified DNA Nucleobases Using Excision Repair
      Enzymes.
AB  - Modification of DNA nucleobases has a profound effect on genome function. We
      developed a method that maps the positions of the modified DNA nucleobases
      throughout genomic DNA. This method couples in vitro nucleobase excision with
      massively parallel DNA sequencing to determine the location of modified DNA
      nucleobases with single base precision. This protocol was used to map uracil
      incorporation and UV photodimers in DNA, and a modification of the protocol has
      been used to map sparse modification events in cells. The Excision-seq protocol
      is broadly applicable to a variety of base modifications for which an excision
      enzyme is available.

PMID- 29043618
TI  - Integrated Microarray-based Tools for Detection of Genomic DNA Damage and Repair
      Mechanisms.
AB  - The genetic information contained within the DNA molecule is highly susceptible
      to chemical and physical insult, caused by both endogenous and exogenous sources
      that can generate in the order of thousands of lesions a day in each of our cells
      (Lindahl, Nature 362(6422):709-715, 1993). DNA damages interfere with DNA
      metabolic processes such as transcription and replication and can be potent
      inhibitors of cell division and gene expression. To combat these regular threats
      to genome stability, a host of DNA repair mechanisms have evolved. When DNA
      lesions are left unrepaired due to defects in the repair pathway, mutations can
      arise that may alter the genetic information of the cell. DNA repair is thus
      fundamental to genome stability and defects in all the major repair pathways can
      lead to cancer predisposition. Therefore, the ability to accurately measure DNA
      damage at a genomic scale and determine the level, position, and rates of removal
      by DNA repair can contribute greatly to our understanding of how DNA repair in
      chromatin is organized throughout the genome. For this reason, we developed the
      3D-DIP-Chip protocol described in this chapter. Conducting such measurements has
      potential applications in a variety of other fields, such as genotoxicity testing
      and cancer treatment using DNA damage inducing chemotherapy. Being able to detect
      and measure genomic DNA damage and repair patterns in individuals following
      treatment with chemotherapy could enable personalized medicine by predicting
      response to therapy.

PMID- 29043619
TI  - Study of UV-induced DNA Repair Factor Recruitment: Kinetics and Dynamics.
AB  - The local UV irradiation technique enables detection, kinetic measurements of
      recruitment, and quantification of DNA Damage Response (DDR) proteins at the site
      of UV-induced DNA damage.Using Isopore filters with high density pores of a broad
      range of sizes, it is possible to UV irradiate and damage only a very small
      portion of the nucleus of a cell by letting UV light pass only through the pores.
      Immunofluorescent analyses of modified DNA nucleotides, proteins, or
      fluorescently tagged versions of target factors can be used as markers to label
      and study UV-induced lesions and their repair.

PMID- 29043620
TI  - Inserting Site-Specific DNA Lesions into Whole Genomes.
AB  - Here, we describe a methodology that allows the insertion of site-specific DNA
      lesions into genomes in living cells. The technique involves the integration of a
      plasmid containing a site-specific lesion engineered in vitro into a precise
      location in the genome via the site-specific recombination reaction from phage
      lambda. The notion of DNA lesion is not restricted to chemically modified
      nucleotides but also refers to unusual DNA structures. This method will be
      instrumental to study qualitatively and quantitatively the genetic consequences
      of site-specific lesions in vivo; moreover, it does also allow analyzing the
      molecular structure of stalled replication forks at well-defined locations.

PMID- 29043621
TI  - A qPCR-Based Protocol to Quantify DSB Resection.
AB  - The nucleolytic degradation of the 5'-ending strand of a Double-Strand DNA break
      (DSB) is necessary to initiate homologous recombination to correctly repair the
      break. This process is called DNA end resection and it is finely regulated to
      prevent genome rearrangements. Here, we describe a protocol to quantify DSB
      resection rate by qPCR, which could be applied to every organisms whenever the
      break site and its flanking region sequences are known.

PMID- 29043622
TI  - Alkaline Denaturing Southern Blot Analysis to Monitor Double-Strand Break
      Processing.
AB  - Generation of 3' single-stranded DNA (ssDNA) tails at the ends of a double-strand
      break (DSB) is essential to repair the break through accurate homology-mediated
      repair pathways. Several methods have been developed to measure ssDNA
      accumulation at a DSB in the budding yeast Saccharomyces cerevisiae. Here, we
      describe one of these assays, which is based on the inability of restriction
      enzymes to cleave ssDNA. Digestion of genomic DNA prepared at different time
      points after DSB generation leads to the formation of ssDNA fragments whose
      length increases as the 5' strand degradation proceeds beyond restriction sites.
      After the separation by electrophoresis on alkaline denaturing agarose gel, these
      ssDNA fragments can be visualized by hybridization with an RNA probe that anneals
      with the 3'-undegraded DSB strand. This assay allows a direct and comprehensive
      visualization of DSB end processing.

PMID- 29043623
TI  - Single Molecule Analysis of Resection Tracks.
AB  - Homologous recombination is initiated by the so-called DNA end resection, the 5'
      3' nucleolytic degradation of a single strand of the DNA at each side of the
      break. The presence of resected DNA is an obligatory step for homologous
      recombination. Moreover, the amount of resected DNA modulates the prevalence of
      different recombination pathways. In different model organisms, there are several
      published ways to visualize and measure with more or less detail the amount of
      DNA resected. In human cells, however, technical constraints hampered the study
      of resection at high resolution. Some information might be gathered from the
      study of endonuclease-created DSBs, in which the resection of breaks at known
      sites can be followed by PCR or ChIP. In this chapter, we describe in detail a
      novel assay to study DNA end resection in breaks located on unknown positions.
      Here, we use ionizing radiation to induce double-strand breaks, but the same
      approach can be used to monitor resection induced by different DNA damaging
      agents. By modifying the DNA-combing technique, used for high-resolution
      replication analyses, we can measure resection progression at the level of
      individual DNA fibers. Thus, we named the method Single Molecule Analysis of
      Resection Tracks (SMART). We use human cells in culture as a model system, but in
      principle the same approach would be feasible to any model organism adjusting
      accordingly the DNA isolation part of the protocol.

PMID- 29043624
TI  - Mapping DNA Breaks by Next-Generation Sequencing.
AB  - Here, we present two approaches to map DNA double-strand breaks (DSBs) and single
      strand breaks (SSBs) in the genome of human cells. We named these methods
      respectively DSB-Seq and SSB-Seq. We tested the DSB and SSB-Seq in HCT1116, human
      colon cancer cells, and validated the results using the topoisomerase 2 (Top2)
      poisoning agent etoposide (ETO). These methods are powerful tools for the direct
      detection of the physiological and pathological "breakome" of the DNA in human
      cells.

PMID- 29043625
TI  - Genome-Wide Profiling of DNA Double-Strand Breaks by the BLESS and BLISS Methods.
AB  - DNA double-strand breaks (DSBs) are major DNA lesions that are constantly formed
      during physiological processes such as DNA replication, transcription, and
      recombination, or as a result of exogenous agents such as ionizing radiation,
      radiomimetic drugs, and genome editing nucleases. Unrepaired DSBs threaten
      genomic stability by leading to the formation of potentially oncogenic
      rearrangements such as translocations. In past few years, several methods based
      on next-generation sequencing (NGS) have been developed to study the genome-wide
      distribution of DSBs or their conversion to translocation events. We developed
      Breaks Labeling, Enrichment on Streptavidin, and Sequencing (BLESS), which was
      the first method for direct labeling of DSBs in situ followed by their genome
      wide mapping at nucleotide resolution (Crosetto et al., Nat Methods 10:361-365,
      2013). Recently, we have further expanded the quantitative nature, applicability,
      and scalability of BLESS by developing Breaks Labeling In Situ and Sequencing
      (BLISS) (Yan et al., Nat Commun 8:15058, 2017). Here, we first present an
      overview of existing methods for genome-wide localization of DSBs, and then focus
      on the BLESS and BLISS methods, discussing different assay design options
      depending on the sample type and application.

PMID- 29043626
TI  - DNA Replication Profiling Using Deep Sequencing.
AB  - Profiling of DNA replication during progression through S phase allows a
      quantitative snap-shot of replication origin usage and DNA replication fork
      progression. We present a method for using deep sequencing data to profile DNA
      replication in S. cerevisiae.

PMID- 29043627
TI  - Quantitative Bromodeoxyuridine Immunoprecipitation Analyzed by High-Throughput
      Sequencing (qBrdU-Seq or QBU).
AB  - Incorporation into DNA of nucleoside analogs like 5-bromo-2'-deoxyuridine (BrdU)
      is a powerful tool for in vivo studies of DNA synthesis during replication and
      repair. Immunoprecipitation of BrdU-labeled DNA analyzed by DNA sequencing (BrdU
      IP-seq) allows for genome-wide, sequence-specific tracking of replication origin
      and replication fork dynamics under different conditions, such as DNA damage and
      replication stress, and in mutant strains. We have recently developed a
      quantitative method for BrdU-IP-seq (qBrdU-seq) involving DNA barcoding to enable
      quantitative analysis of multiple experimental samples subjected to BrdU-IP-seq.
      After initial barcoding of multiple, individually BrdU-labeled genomic DNA
      samples, a pooling strategy is used for all subsequent steps including
      immunoprecipitation, amplification, and sequencing, which eliminates sample-to
      sample variability in these steps. Parallel processing of an aliquot of the
      pooled input sample provides a direct control for the normalization of the data
      and yields results that allow quantitative comparisons of the experimental
      samples. Though developed for the analysis of S. cerevisiae, this method should
      be directly adaptable to other model systems.

PMID- 29043628
TI  - Strand-Specific Analysis of DNA Synthesis and Proteins Association with DNA
      Replication Forks in Budding Yeast.
AB  - DNA replication initiates at DNA replication origins after unwinding of double
      strand DNA(dsDNA) by replicative helicase to generate single-stranded DNA (ssDNA)
      templates for the continuous synthesis of leading-strand and the discontinuous
      synthesis of lagging-strand. Therefore, methods capable of detecting strand
      specific information will likely yield insight into the association of proteins
      at leading and lagging strand of DNA replication forks and the regulation of
      leading and lagging strand synthesis during DNA replication. The enrichment and
      Sequencing of Protein-Associated Nascent DNA (eSPAN), which measure the relative
      amounts of proteins at nascent leading and lagging strands of DNA replication
      forks, is a step-wise procedure involving the chromatin immunoprecipitation
      (ChIP) of a protein of interest followed by the enrichment of protein-associated
      nascent DNA through BrdU immunoprecipitation. The isolated ssDNA is then
      subjected to strand-specific sequencing. This method can detect whether a protein
      is enriched at leading or lagging strand of DNA replication forks. In addition to
      eSPAN, two other strand-specific methods, (ChIP-ssSeq), which detects potential
      protein-ssDNA binding and BrdU-IP-ssSeq, which can measure synthesis of both
      leading and lagging strand, were developed along the way. These methods can
      provide strand-specific and complementary information about the association of
      the target protein with DNA replication forks as well as synthesis of leading and
      lagging strands genome wide. Below, we describe the detailed eSPAN, ChIP-ssSeq,
      and BrdU-IP-ssSeq protocols.

PMID- 29043630
TI  - Dynamic Architecture of Eukaryotic DNA Replication Forks In Vivo, Visualized by
      Electron Microscopy.
AB  - The DNA replication process can be heavily perturbed by several different
      conditions of genotoxic stress, particularly relevant for cancer onset and
      therapy. The combination of psoralen crosslinking and electron microscopy has
      proven instrumental to reveal the fine architecture of in vivo DNA replication
      intermediates and to uncover their remodeling upon specific conditions of
      genotoxic stress. The replication structures are stabilized in vivo (by psoralen
      crosslinking) prior to extraction and enrichment procedures, allowing their
      visualization at the transmission electron microscope. This chapter outlines the
      procedures required to visualize and interpret in vivo replication intermediates
      of eukaryotic genomic DNA, and includes an improved method for enrichment of
      replication intermediates, compared to previously used BND-cellulose columns.

PMID- 29043629
TI  - Analysis of Replicative Polymerase Usage by Ribonucleotide Incorporation.
AB  - Mapping the usage of replicative DNA polymerases has previously proved to be
      technically challenging. By exploiting mutant polymerases that incorporate
      ribonucleotides into the DNA with a significantly higher proficiency than their
      wild-type counterparts, we and others have developed methods that can identify
      what proportion of each DNA strand (i.e., the Watson and Crick strands) is
      replicated by a specific DNA polymerase. The incorporation of excess
      ribonucleotides by a mutated polymerase effectively marks, in each individual
      cells, the DNA strand that is replicated by that specific mutated polymerase.
      Changes to DNA polymerase usage can be examined at specific loci by Southern blot
      analysis while a global analysis of polymerase usage can be achieved by applying
      next-generation sequencing. This genome-wide data also provides a direct measure
      of replication origin efficiency and can be used to indirectly calculate
      replication timing.

PMID- 29043631
TI  - A Molecular Toolbox to Engineer Site-Specific DNA Replication Perturbation.
AB  - Site-specific arrest of DNA replication is a useful tool for analyzing cellular
      responses to DNA replication perturbation. The E. coli Tus-Ter replication
      barrier can be reconstituted in eukaryotic cells as a system to engineer an
      unscheduled collision between a replication fork and an "alien" impediment to DNA
      replication. To further develop this system as a versatile tool, we describe a
      set of reagents and a detailed protocol that can be used to engineer Tus-Ter
      barriers into any locus in the budding yeast genome. Because the Tus-Ter complex
      is a bipartite system with intrinsic DNA replication-blocking activity, the
      reagents and protocols developed and validated in yeast could also be optimized
      to engineer site-specific replication fork barriers into other eukaryotic cell
      types.

PMID- 29043632
TI  - Single Cell Gel Electrophoresis for the Detection of Genomic Ribonucleotides.
AB  - Single cell gel electrophoresis or comet assay enables the quantification of DNA
      damage such as single-strand or double-strand breaks on a single cell level.
      Here, we describe a variant of this method for the detection of ribonucleotides
      embedded in genomic DNA. Briefly, cells are embedded in agarose on a microscopic
      slide, lysed under high salt and alkaline conditions and then subjected to in
      situ treatment with E. coli RNase HII which nicks 5' to a ribonucleotide within
      the context of a DNA duplex thereby converting genomic ribonucleotides into
      strand breaks. After unwinding of genomic DNA using a highly alkaline buffer,
      electrophoresis under mild alkaline conditions is performed resulting in
      formation of comets due to migration of fragmented DNA toward the anode.
      Following SYBR Gold staining comets can be visualized by fluorescence microscopy.
      In this setting, the length and the intensity of comets formed reflect the level
      of genomic ribonucleotides present in a given cell.

PMID- 29043633
TI  - Measuring the Levels of Ribonucleotides Embedded in Genomic DNA.
AB  - Ribonucleotides (rNTPs) are incorporated into genomic DNA at a relatively high
      frequency during replication. They have beneficial effects but, if not removed
      from the chromosomes, increase genomic instability. Here, we describe a fast
      method to easily estimate the amounts of embedded ribonucleotides into the
      genome. The protocol described is performed in Saccharomyces cerevisiae and
      allows us to quantify altered levels of rNMPs due to different mutations in the
      replicative polymerase epsilon. However, this protocol can be easily applied to
      cells derived from any organism.

PMID- 29043634
TI  - Mapping Ribonucleotides Incorporated into DNA by Hydrolytic End-Sequencing.
AB  - Ribonucleotides embedded within DNA render the DNA sensitive to the formation of
      single-stranded breaks under alkali conditions. Here, we describe a next
      generation sequencing method called hydrolytic end sequencing (HydEn-seq) to map
      ribonucleotides inserted into the genome of Saccharomyce cerevisiae strains
      deficient in ribonucleotide excision repair. We use this method to map several
      genomic features in wild-type and replicase variant yeast strains.

PMID- 29043635
TI  - Detection of DNA-RNA Hybrids In Vivo.
AB  - DNA-RNA hybrids form naturally during essential cellular functions such as
      transcription and replication. However, they may be an important source of genome
      instability, a hallmark of cancer and genetic diseases. Detection of DNA-RNA
      hybrids in cells is becoming crucial to understand an increasing number of
      molecular biology processes in genome dynamics and function and to identify new
      factors and mechanisms responsible for disease in biomedical research. Here, we
      describe two different procedures for the reliable detection of DNA-RNA hybrids
      in the yeast Saccharomyces cerevisiae and in human cells: DNA-RNA
      Immunoprecipitation (DRIP) and Immunofluorescence.

PMID- 29043636
TI  - Analysis of De Novo Telomere Addition by Southern Blot.
AB  - Telomere length is maintained in most eukaryotes by the action of a specialized
      enzyme, the telomerase. However, the complexity of mechanisms regulating
      telomeric DNA length as well as the heterogeneity in length of each telomere in a
      population of cells has made it very difficult to understand how telomerase is
      regulated in vivo. Here, we describe a method developed in Saccharomyces
      cerevisiae to monitor the addition of telomeric sequences to a single newly
      generated telomere in vivo. The primary strain consists of a HO endonuclease
      cleavage site that is placed directly adjacent to an 81-base-pair stretch of
      telomeric DNA inserted into the ADH4 locus of chromosome VII. Upon cleavage by
      HO, the de novo DNA end is rapidly healed by the telomerase enzyme and the
      analysis of this process allows to gain a mechanistic understanding of how
      telomerase action is regulated in the cell.

PMID- 29043637
TI  - Assays to Study Repair of Inducible DNA Double-Strand Breaks at Telomeres.
AB  - The ends of linear chromosomes are constituted of repetitive DNA sequences called
      telomeres. Telomeres, nearby regions called subtelomeres, and their associated
      factors prevent chromosome erosion over cycles of DNA replication and prevent
      chromosome ends from being recognized as DNA double-strand breaks (DSBs). This
      raises the question of how cells repair DSBs that actually occur near chromosome
      ends. One approach is to edit the genome and engineer cells harboring inducible
      DSB sites within the subtelomeric region of different chromosome ends. This
      provides a reductionist and tractable genetic model system in which mechanisms
      mediating repair can be dissected via genetics, molecular biology, and microscopy
      tools.

PMID- 29043638
TI  - Telomerase RNA Imaging in Budding Yeast and Human Cells by Fluorescent In Situ
      Hybridization.
AB  - Telomerase, the enzyme that elongates telomeres in most eukaryotes, is a
      ribonucleoprotein complex composed of a reverse transcriptase catalytic subunit
      (TERT in human, Est2 in the budding yeast S. cerevisiae), regulatory factors and
      a noncoding RNA called hTERC (in human) or TLC1 (in budding yeast). Telomerase
      trafficking is a major process in the biogenesis and regulation of telomerase
      action at telomeres. Due to its higher signal-to-noise ratio, imaging of the
      telomerase RNA moiety is frequently used to determine telomerase intracellular
      localization. Here we describe how to image telomerase RNA in human and yeast
      cells using fluorescence in situ hybridization.

PMID- 29043639
TI  - Methods to Study Repeat Fragility and Instability in Saccharomyces cerevisiae.
AB  - Trinucleotide repeats are common in the human genome and can undergo changes in
      repeat length. Expanded CAG repeats have been linked to over 14 human diseases
      and are considered hotspots for breakage and genomic rearrangement. Here, we
      describe two Saccharomyces cerevisiae based assays that evaluate the rate of
      chromosome breakage that occurs within a repeat tract (fragility), and a PCR
      based assay to evaluate tract length changes (instability). The first fragility
      assay utilizes end-loss and subsequent telomere addition as the main mode of
      repair of a yeast artificial chromosome (YAC). The second fragility assay relies
      on the fact that a chromosomal break stimulates recombination-mediated repair. In
      addition to understanding the role of fragility at repetitive DNA sequences, both
      assays can be modified to evaluate instability of a CAG repeat using a PCR-based
      assay. All three assays have been essential in understanding the genetic
      mechanisms that cause chromosome breaks and tract-length changes at unstable
      repeats.

PMID- 29043640
TI  - Quantitative Analysis of the Rates for Repeat-Mediated Genome Instability in a
      Yeast Experimental System.
AB  - Instability of repetitive DNA sequences causes numerous hereditary disorders in
      humans, the majority of which are associated with trinucleotide repeat
      expansions. Here, we describe a unique system to study instability of triplet
      repeats in a yeast experimental setting. Using fluctuation assay and the novel
      program FluCalc we are able to accurately estimate the rates of large-scale
      expansions, as well as repeat-mediated mutagenesis and gross chromosomal
      rearrangements for different repeat sequences.

PMID- 29043641
TI  - Measuring Dynamic Behavior of Trinucleotide Repeat Tracts In Vivo in
      Saccharomyces cerevisiae.
AB  - Trinucleotide repeat (TNR) tracts are inherently unstable during DNA replication,
      leading to repeat expansions and/or contractions. Expanded tracts are the cause
      of over 40 neurodegenerative and neuromuscular diseases. In this chapter, we
      focus on the (CNG)n repeat sequences that, when expanded, lead to Huntington's
      disease (HD), myotonic dystrophy type 1 (DM1), and a number of other
      neurodegenerative diseases. We describe a series of in vivo assays, using the
      model system Saccharomyces cerevisiae, to determine and characterize the dynamic
      behavior of TNR tracts that are in the early stages of expansion, i.e., the so
      called threshold range. Through a series of time courses and PCR-based assays,
      dynamic changes in tract length can be observed as a function of time. These
      assays can ultimately be used to determine how genetic factors influence the
      process of tract expansion in these early stages.

PMID- 29043642
TI  - The Detection and Analysis of Chromosome Fragile Sites.
AB  - A fragile site is a chromosomal locus that is prone to form a gap or constriction
      visible within a condensed metaphase chromosome, particularly following exposure
      of cells to DNA replication stress. Based on their frequency, fragile sites are
      classified as either common (CFSs; present in all individuals) or rare (RFSs;
      present in only a few individuals). Interest in fragile sites has remained high
      since their discovery in 1965, because of their association with human disease.
      CFSs are recognized as drivers of oncogene activation and genome instability in
      cancer cells, while some RFSs are associated with neurodegenerative diseases.
      This review summaries our current understanding of the nature and causes of
      fragile site "expression", including the recently characterized phenomenon of
      telomere fragility. In particular, we focus on a description of the methodologies
      and technologies for detection and analysis of chromosome fragile sites.

PMID- 29043643
TI  - Imaging of DNA Ultrafine Bridges in Budding Yeast.
AB  - DNA ultrafine bridges (UFBs) are a type of chromatin-free DNA bridges that
      connect sister chromatids in anaphase and pose a threat to genome stability.
      However, little is known about the origin of these structures, and how they are
      sensed and resolved by the cell. In this chapter, we review tools and methods for
      studying UFBs by fluorescence microscopy including chemical and genetic
      approaches to induce UFBs in the model organism Saccharomyces cerevisiae.

PMID- 29043644
TI  - Detection of Ultrafine Anaphase Bridges.
AB  - Ultrafine anaphase bridges (UFBs) are thin DNA threads linking the separating
      sister chromatids in the anaphase of mitosis. UFBs are thought to form when
      topological DNA entanglements between two chromatids are not resolved prior to
      anaphase onset. In contrast to other markers of defective chromosome segregation,
      UFBs cannot be detected by direct staining of the DNA, but instead can be
      detected using immunofluorescence-based approaches. Due to the fact that they are
      short-lived and fragile in nature, UFBs can be challenging to detect. In this
      chapter, we describe methods that have been optimized for successful detection of
      UFBs. We also provide guidelines for the optimization of UFBs detection depending
      on the antibody and the cell line to be used.

PMID- 29043645
TI  - A Chromatin Fiber Analysis Pipeline to Model DNA Synthesis and Structures in
      Fission Yeast.
AB  - Chromatin fibers, first described by Jackson and Pombo (J Cell Biol 140(6):1285
      1295, 1998) are prepared from cells lysed on glass coverslips, and require
      minimal equipment to produce. Since the DNA is not previously treated with
      denaturing agents, proteins are left intact and may be used to model other DNA
      based processes. Such an analysis can be daunting, without a rigorous method for
      analysis. We describe a pipeline for chromatin fiber use to model DNA replication
      complexes. Full protocols for chromatin fiber preparation and staining are
      presented. Further, we have developed an analysis algorithm for One Dimensional
      Data-Boolean Logic Operations Binning System (ODD-BLOBS). This freely available
      software defines replication and protein tracts, measures their lengths, and then
      correlates replicated areas with protein distributions. Our methods and analysis
      are tested in Schizosaccharomyces pombe (fission yeast) but may be applied to
      model replication structures across multiple organisms.

PMID- 29043646
TI  - Long-Term Imaging of DNA Damage and Cell Cycle Progression in Budding Yeast Using
      Spinning Disk Confocal Microscopy.
AB  - Live cell imaging can monitor biological processes in time and space by providing
      quantitative measurements of cell behavior on a single-cell basis and in live
      conditions. However the illumination required to visualize fluorescently tagged
      endogenous proteins often perturbs cellular physiology, a problem particularly
      acute for yeast cells that are small, highly photosensitive and with scarce
      protein content. Analyzing the activation of the DNA damage response (DDR) in
      various yeast mutants or growth conditions, as well as its consequences for cell
      cycle progression and cell viability over extended periods of time therefore
      requires a special microscopy setup that does not by itself create DNA damage or
      perturb cell growth. Here, we provide a quick guide, strains and advice for
      imaging the DDR in S. cerevisiae for extended time (3-12 h) using spinning-disk
      confocal microscopy in conditions of limited photobleaching and photodamage. DDR
      is a conserved mechanism that allows the cell to respond to various stresses,
      especially those altering DNA integrity or topology. Acquiring time-lapse images
      of the DDR at high temporal and spatial resolution is of great interest, in
      particular when studying the effects of mutations or drugs which compromise
      genomic stability and cell cycle progression.

PMID- 29043647
TI  - The CellClamper: A Convenient Microfluidic Device for Time-Lapse Imaging of
      Yeast.
AB  - Time-lapse fluorescence imaging of yeast cells allows the study of multiple
      fluorescent targets in single cells, but is often hampered by the tedious
      cultivation using agar pads or glass bottom wells. Here, we describe the
      fabrication and operation of a microfluidic device for long-term imaging of yeast
      cells under constant or changing media conditions. The device allows acquisition
      of high quality images as cells are fixed in a two-dimensional imaging plane.
      Four yeast strains can be analyzed simultaneously over several days while up to
      four different media can be flushed through the chip. The microfluidic device
      does not rely on specialized equipment for its operation. To illustrate the use
      of the chip in DNA damage research, we show how common readouts for DNA damage or
      genomic instability behave upon induction with genotoxic chemicals (MMS, HU) or
      induction of a single double-strand break using induced CRISPR-Cas9 expression.

PMID- 29043648
TI  - Characterization of Structural and Configurational Properties of DNA by Atomic
      Force Microscopy.
AB  - We describe a method to extract quantitative information on DNA structural and
      configurational properties from high-resolution topographic maps recorded by
      atomic force microscopy (AFM). DNA molecules are deposited on mica surfaces from
      an aqueous solution, carefully dehydrated, and imaged in air in Tapping Mode.
      Upon extraction of the spatial coordinates of the DNA backbones from AFM images,
      several parameters characterizing DNA structure and configuration can be
      calculated. Here, we explain how to obtain the distribution of contour lengths,
      end-to-end distances, and gyration radii. This modular protocol can be also used
      to characterize other statistical parameters from AFM topographies.

PMID- 29043649
TI  - Genome-Wide Quantitative Fitness Analysis (QFA) of Yeast Cultures.
AB  - We provide a detailed protocol for robot-assisted, genome-wide measurement of
      fitness in the model yeast Saccharomyces cerevisiae using Quantitative Fitness
      Analysis (QFA). We first describe how we construct thousands of double or triple
      mutant yeast strains in parallel using Synthetic Genetic Array (SGA) procedures.
      Strains are inoculated onto solid agar surfaces by liquid spotting followed by
      repeated photography of agar plates. Growth curves are constructed and the
      fitness of each strain is estimated. Robot-assisted QFA, can be used to identify
      genetic interactions and chemical sensitivity/resistance in genome-wide
      experiments, but QFA can also be used in smaller scale, manual workflows.

PMID- 29043650
TI  - Rewiring the Budding Yeast Proteome using Synthetic Physical Interactions.
AB  - Artificially tethering two proteins or protein fragments together is a powerful
      method to query molecular mechanisms. However, this approach typically relies
      upon a prior understanding of which two proteins, when fused, are most likely to
      provide a specific function and is therefore not readily amenable to large-scale
      screening. Here, we describe the Synthetic Physical Interaction (SPI) method to
      create proteome-wide forced protein associations in the budding yeast
      Saccharomyces cerevisiae. This method allows thousands of protein-protein
      associations to be screened for those that affect either normal growth or
      sensitivity to drugs or specific conditions. The method is amenable to proteins,
      protein domains, or any genetically encoded peptide sequence.

PMID- 29043651
TI  - Reporter-Based Synthetic Genetic Array Analysis: A Functional Genomics Approach
      for Investigating Transcript or Protein Abundance Using Fluorescent Proteins in
      Saccharomyces cerevisiae.
AB  - Fluorescent reporter genes have long been used to quantify various cell features
      such as transcript and protein abundance. Here, we describe a method, reporter
      synthetic genetic array (R-SGA) analysis, which allows for the simultaneous
      quantification of any fluorescent protein readout in thousands of yeast strains
      using an automated pipeline. R-SGA combines a fluorescent reporter system with
      standard SGA analysis and can be used to examine any array-based strain
      collection available to the yeast community. This protocol describes the R-SGA
      methodology for screening different arrays of yeast mutants including the
      deletion collection, a collection of temperature-sensitive strains for the
      assessment of essential yeast genes and a collection of inducible overexpression
      strains. We also present an alternative pipeline for the analysis of R-SGA output
      strains using flow cytometry of cells in liquid culture. Data normalization for
      both pipelines is discussed.

PMID- 29043652
TI  - Statistical Analysis and Quality Assessment of ChIP-seq Data with DROMPA.
AB  - Chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis can
      detect protein/DNA-binding and histone-modification sites across an entire
      genome. As there are various factors during sample preparation that affect the
      obtained results, multilateral quality assessments are essential. Here, we
      describe a step-by-step protocol using DROMPA, a program for user-friendly ChIP
      seq pipelining. DROMPA can be used for quality assessment, data normalization,
      visualization, peak calling, and multiple statistical analyses.

PMID- 29043653
TI  - Quantitative Analysis of DNA Damage Signaling Responses to Chemical and Genetic
      Perturbations.
AB  - Phosphorylation-mediated signaling is essential for maintenance of the eukaryotic
      genome. The evolutionarily conserved kinases ATR and ATM sense specific DNA
      structures generated upon DNA damage or replication stress and mediate an
      extensive signaling network that impinges upon most nuclear processes. ATR/ATM
      signaling is highly regulated and can function in a context-dependent manner.
      Thus, the ability to quantitatively monitor most, if not all, signaling events in
      this network is essential to investigate the mechanisms by which kinases maintain
      genome integrity. Here we describe a method for the Quantitative Mass
      Spectrometry Analysis of Phospho-Substrates (QMAPS) to monitor in vivo DNA damage
      signaling in a systematic, unbiased, and quantitative manner. Using the model
      organism Saccharomyces cerevisiae, we provide an example for how QMAPS can be
      applied to define the effect of genotoxins, illustrating the importance of
      quantitatively monitoring multiple kinase substrates to comprehensively
      understanding kinase action. QMAPS can be easily extended to other organisms or
      signaling pathways where kinases can be deleted or inhibited.

PMID- 29043654
TI  - Evaluation of Selected MicroRNAs Expression in Remission Phase of Multiple
      Sclerosis and Their Potential Link to Cognition, Depression, and Disability.
AB  - Accumulating data suggests that miRNAs might play a major role in
      neuroinflammatory processes. Therefore, our study aimed to first estimate the
      levels of miR-155, miR-326, and miR-301a in serum of RR-MS patients in the
      remission phase and then compare the levels of the examined miRNAs at different
      times after relapse. In this study, 36 RR-MS patients in the remission phase took
      part. We analyzed two subgroups of RR-MS: one, 1 to 2 months after completing
      steroid treatment during relapse (post-acute; n = 13) and the other, over 2 years
      without any relapse (stable; n = 23). Moreover, we made correlations between
      these biochemical results and clinical parameters of cognitive impairment,
      depression, and disability. The obtained results presented downregulation of miR
      155 and miR-301a (in 94% and 51% samples, respectively) and overexpression of miR
      326 (in 72% samples) in RR-MS patients. Moreover, we observed a positive
      correlation between the relative expression of miRNAs and BDI (Beck Depression
      Index) for miR-326 (rho = 0.385459, p = 0.022210; Spearman's rank correlation)
      and miR-301a (rho = 0.435131, p = 0.008991; Spearman rank correlation). We also
      observed the differences in expression levels between the post-acute and stable
      phases of RR-MS. The expression levels of miR-301a and miR155 were higher in the
      post-acute vs. stable phase of remission (2.385 vs. 0.524 and 0.594 vs. 0.147;
      respectively). Our study, for the first time, presents miRNA expression
      differences in two stages of remission: post-acute and stable.

PMID- 29043655
TI  - Above, on, or shang ()? Language and spatial representations among English
      Mandarin bilinguals.
AB  - This study investigated if exposure to spatial language could affect spatial
      cognition in English-Mandarin bilinguals by focusing on contact/noncontact
      distinctions, an area that has been a source of contention in the language-and
      thought literature. Sixty-three participants were first primed with sentences
      containing spatial terms (e.g., above, on) before performing a spatial decision
      task. Approximately half of the participants (n = 33) were primed in English; for
      the remaining participants (n = 30), primes comprising Mandarin spatial terms
      which mark spatial distinctions differently than in English (e.g., shang in
      Mandarin signifies both above and on in English)-were employed instead. Our
      findings revealed that participants' performance was influenced by spatial primes
      in the English experiment, thereby proffering evidence for thinking-for-speaking
      effects. However, these findings were not mirrored for the Mandarin experiment,
      confirming that the contact/noncontact specificity of spatial terms may have been
      instrumental in engendering the thinking-for-speaking effects observed in
      English.

PMID- 29043656
TI  - From eyes to hands: Transfer of learning in the Simon task across motor
      effectors.
AB  - Inhibition of irrelevant and conflicting information and responses is crucial for
      goal-directed behaviour and adaptive functioning. In the Simon task, for example,
      responses are slowed if their mappings are spatially incongruent with stimuli
      that must be discriminated on a nonspatial dimension. Previous work has shown
      that practice with incongruent spatial mappings can reduce or even reverse the
      Simon effect. We asked whether such practice transfers between the manual and
      oculomotor systems and if so to what extent this occurs across a range of
      behavioural tasks. In two experiments, one cohort of participants underwent anti
      saccade training, during which they repeatedly inhibited the reflexive impulse to
      look toward a briefly presented target. Additionally, two active-control training
      groups were included, in which participants either trained on Pro-saccade or
      Fixation training regimens. In Experiment 1, we probed whether the Simon effect
      and another inhibitory paradigm, the Stroop task, showed differential effects
      after training. In Experiment 2, we included a larger battery of inhibitory tasks
      (Simon, Stroop, flanker and stop-signal) and noninhibitory control measures
      (multitasking and visual search) to assess the limits of transfer. All three
      training regimens led to behavioural improvements in the trained-upon task, but
      only the anti-saccade training group displayed benefits that transferred to the
      manual response modality. This transfer of training benefit replicated across the
      two experiments but was restricted to the Simon effect. Evidence for transfer of
      inhibition training across motor systems offers important insights into the
      nature of stimulus-response representations and their malleability.

PMID- 29043657
TI  - Confidence in masked orientation judgments is informed by both evidence and
      visibility.
AB  - How do human observers determine their degree of belief that they are correct in
      a decision about a visual stimulus-that is, their confidence? According to
      prominent theories of confidence, the quality of stimulation should be positively
      related to confidence in correct decisions, and negatively to confidence in
      incorrect decisions. However, in a backward-masked orientation task with a
      varying stimulus onset asynchrony (SOA), we observed that confidence in incorrect
      decisions also increased with stimulus quality. Model fitting to our decision and
      confidence data revealed that the best explanation for the present data was the
      new weighted evidence-and-visibility model, according to which confidence is
      determined by evidence about the orientation as well as by the general visibility
      of the stimulus. Signal detection models, postdecisional accumulation models, two
      channel models, and decision-time-based models were all unable to explain the
      pattern of confidence as a function of SOA and decision correctness. We suggest
      that the metacognitive system combines several cues related to the correctness of
      a decision about a visual stimulus in order to calculate decision confidence.

PMID- 29043658
TI  - Erratum to: Isolation and Characterization of Aortic Dendritic Cells and
      Lymphocytes in Atherosclerosis.

PMID- 29043659
TI  - Magnitude of Muscle Strength and Mass Adaptations Between High-Load Resistance
      Training Versus Low-Load Resistance Training Associated with Blood-Flow
      Restriction: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Low-load resistance training (< 50% of one-repetition maximum [1RM])
      associated with blood-flow restriction (BFR-RT) has been thought to promote
      increases in muscle strength and mass. However, it remains unclear if the
      magnitude of these adaptations is similar to conventional high-load resistance
      training (> 65% 1RM; HL-RT). OBJECTIVE: To compare the effects of HL- versus BFR
      RT on muscle adaptations using a systematic review and meta-analysis procedure.
      METHODS: Studies were identified via electronic databases based on the following
      inclusion criteria: (a) pre- and post-training assessment of muscular strength;
      (b) pre- and post-training assessment of muscle hypertrophy; (c) comparison of HL
      RT vs. BFR-RT; (d) score >= 4 on PEDro scale; (e) means and standard deviations
      (or standard errors) are reported from absolute values or allow estimation from
      graphs. If this last criterion was not met, data were directly requested from the
      authors. RESULTS: The main results showed higher increases in muscle strength for
      HL- as compared with BFR-RT, even when considering test specificity, absolute
      occlusion pressure, cuff width, and occlusion pressure prescription. Regarding
      the hypertrophic response, results revealed similar effects between HL- and BFR
      RT, regardless of the absolute occlusion pressure, cuff width, and occlusion
      pressure prescription. CONCLUSIONS: Based on the present data, maximum muscle
      strength may be optimized by specific training methods (i.e., HL-RT) while both
      HL- and BFR-RT seem equally effective in increasing muscle mass. Importantly, BFR
      RT is a valid and effective approach for increasing muscle strength in a wide
      spectrum of ages and physical capacity, although it may seem particularly of
      interest for those individuals with physical limitations to engage in HL-RT.

PMID- 29043660
TI  - Sera of Peruvians with fever of unknown origins include viral nucleic acids from
      non-vertebrate hosts.
AB  - Serum samples collected from 88 Peruvians with unexplained fever were analyzed
      for viral sequences using metagenomics. Nucleic acids of anelloviruses, pegivirus
      A (GBV-C), HIV, Dengue virus, and Oropouche virus were detected. We also
      characterized from two sera the RNA genomes of new species of partitivirus and
      dicistrovirus belonging to viral families known to infect fungi or arthropod,
      respectively. Genomic DNA of a putative fungal cellular host could be PCR
      amplified from the partitivirus-containing serum sample. The detection in human
      serum of nucleic acids from viral families not known to infect vertebrates may
      indicate contamination during sample collection and aliquoting or human infection
      by their presumed cellular host, here a fungus. The role, if any, of the non
      vertebrate infecting viruses detected in serum in inducing fever is unknown.

PMID- 29043662
TI  - Stryphnodendron adstringens ("Barbatimao") Leaf Fraction: Chemical
      Characterization, Antioxidant Activity, and Cytotoxicity Towards Human Breast
      Cancer Cell Lines.
AB  - We evaluated the chemical composition, antioxidant activity, and antitumor
      potential of a fraction that was isolated from Stryphnodendron adstringens
      (barbatimao) leaf aqueous extract. Fraction is composed by gallic acid,
      procyanidin dimer B1, and (-)-epicatechin-3-O-gallate and it exhibits antioxidant
      and cytotoxic activities. Fraction was cytotoxic against two human breast cancer
      cell lines, ER (+) and MCF-7 and the triple-negative, MDA-MB-435. The
      sulforhodamine B assay showed that, as compared to normal control cells, the
      fraction significantly (P < 0.05) decreased cancer cell viability. The
      morphological alterations noted in the treated cancer cells were cell rounding
      up, shrinkage, and nuclear condensation reduction of cell diameter and length.
      Treatment with fraction increased cancer cell expression of Bax, caspase-9,
      active caspase-3, caspase-8, LC-3, and beclin-1 and decreased Bcl-2, caspase-3,
      and pro-caspase-8 expression. Altogether, fraction is cytotoxic to both breast
      cancer cell lines, induces cell death, and its mechanism of action seems to
      include the induction of apoptosis. Our data support a positive role of the
      fraction as a chemopreventive agent for antineoplastic drug development.

PMID- 29043661
TI  - Development of Adenosine Deaminase-Specific IgY Antibodies: Diagnostic and
      Inhibitory Application.
AB  - Adenosine deaminase (ADA) is currently used as a diagnostic marker for
      tuberculous pleuritis. Although ADA has been suggested as a potential marker for
      several types of cancer, the importance of each of ADA isoforms as well as their
      levels and enzymatic activities in tumors need to be further investigated. Herein
      we developed avian immunoglobulin Y highly specific to human ADA via hens
      immunization with calf adenosine deaminase. The obtained antibodies were used for
      the development of a sensitive double-egg yolk immunoglobulin (IgY) sandwich
      ELISA assay with an ADA detection limit of 0.5 ng/ml and a linearity range of up
      to 10 ng/ml. Specific, affinity-purified IgYs were able to recognize human
      recombinant ADA and ADA present in human cancer cell lines. In addition, antigen
      specific IgY antibodies were able to inhibit catalytic activity of calf ADA with
      an IC50 value of 47.48 nM. We showed that generated IgY antibodies may be useful
      for ADA detection, thus acting as a diagnostic agent in immunoenzymatic assays.

PMID- 29043663
TI  - Nephrotoxicity Induced by Cisplatin Intake in Experimental Rats and Therapeutic
      Approach of Using Mesenchymal Stem Cells and Spironolactone.
AB  - Chronic kidney disease may lead to subsequent tissue fibrosis. However, many
      factors can combat injurious stimuli in these tissues aiming to repair, heal, and
      alleviate any disturbance. Chemokines release, migration of inflammatory cells to
      the affected site, and activation of fibroblasts for the production of
      extracellular matrix are commonly observed in this disease. In the last years,
      many studies have focused on spironolactone (SPL), a mineralocorticoid receptor
      antagonist, and its pharmacological effects. In the present study, SPL was
      selected as an anti-inflammatory agent to combat nephrotoxicity and renal
      fibrosis induced by cisplatin. Mesenchymal stem cells (MSCs) were also selected
      in addition as a referring agent. Renal fibrosis induced by cisplatin intake
      significantly increased creatinine, urea, nuclear factor kappa B, insulin-like
      growth factor-1, fibroblast growth factor-23, and kidney malondialdehyde (MDA)
      content. Hepatocyte growth factor and renal content of reduced glutathione
      demonstrated a significant decrease. Histopathological examination of kidney
      tissues demonstrated marked cellular changes which are correlated with the
      biochemical results. Oral SPL intake (20 mg/kg/body weight) daily for 4 weeks and
      MSCs administration (3 * 106 cell/rat) intravenous to the experimental rats
      resulted in a significant improvement of both the biomarkers studied and the
      histopathological profile of the renal tissue. Individual administration of
      spironolactone and MSCs exhibited a marked anti-inflammatory potential and
      alleviated to a great extent the nephrotoxicity and renal fibrotic pattern
      induced by cisplatin.

PMID- 29043664
TI  - Substrate Scope of O-Methyltransferase from Streptomyces peucetius for
      Biosynthesis of Diverse Natural Products Methoxides.
AB  - Methylation is a common post-modification reaction that is observed during the
      biosynthesis of secondary metabolites produced by plants and microorganisms.
      Based on the sequence information from Streptomyces peucetius ATCC27952, a
      putative O-methyltransferase (OMT) gene SpOMT7740 was polymerase chain reaction
      amplified and cloned into E. coli BL21 (DE3) host to test the substrate
      promiscuity and conduct functional characterization. In vitro and in vivo
      reaction assays were carried out over various classes of substrates: flavonoids
      (flavonol, flavones, and isoflavonoid), chalcones, anthraquinones,
      anthracyclines, and sterol molecules, and the applications in synthesizing
      diverse classes of O-methoxy natural products were also illustrated. SpOMT7740
      catalyzed the O-methylation reaction to form various natural and non-natural O
      methoxides, includes 7-hydroxy-8-O-methoxy flavone, 3-O-methoxy flavone, three
      mono-, di-, and tri-O-methoxy genistein, mono-O-methoxy phloretin, mono-O-methoxy
      luteolin, 3-O-methoxy beta-sitosterol, and O-methoxy anthraquinones (emodin and
      aloe emodin) and O-methoxy anthracycline (daunorubicin) exhibiting diverse
      substrate flexibility. Daunorubicin is a native secondary metabolite of S.
      peucetius. Among the compounds tested, 7,8-dihydroxyflavone was the best
      substrate for bioconversion to 7-hydroxy-8-O-methoxy flavone, and it was
      structurally elucidated. This enzyme showed a flexible catalysis over the given
      ranges of temperature, pH, and divalent cationic conditions for O-methylation.

PMID- 29043665
TI  - Labeling the ER for Light and Fluorescence Microscopy.
AB  - The ER is a highly dynamic network of tubules and membrane sheets. Hence imaging
      this organelle in its native and mobile state is of great importance. Here we
      describe methods of labeling the native ER using fluorescent proteins and lipid
      dyes as well as methods for immunolabeling on plant tissue.

PMID- 29043666
TI  - 3D Electron Microscopy of the ER.
AB  - The endoplasmic reticulum (ER) forms an extensive network in plant cells. In leaf
      cells and vacuolated root cells it is mainly restricted to the cortex whereas in
      the root meristem the cortical and cytoplasmic ER takes up a large volume
      throughout the entire cell. Only 3D electron microscopy provides sufficient
      resolution to understand the spatial organization of the ER in the root. However,
      high contrast staining and optimally ER specific staining is essential. Here we
      describe a protocol for selective ER staining that allows automated or
      semiautomated segmentation of the organelle in 3D datasets obtained from serial
      sections, Array Tomography, Serial Block Face Scanning Electron Microscopy
      (SBFSEM), or Focused Ion Beam (FIB) SEM.

PMID- 29043667
TI  - Characterization of Proteins Localized to Plant ER-PM Contact Sites.
AB  - Like in most eukaryotic cells, the plant endoplasmic reticulum (ER) network is
      physically linked to the plasma membrane (PM), forming ER-PM contact sites
      (EPCS). The protein complex required for maintaining the EPCS is composed of ER
      integral membrane proteins (e.g., VAP27, synaptotagmins), PM-associated proteins
      (e.g., NET3C), and the cytoskeleton. Here, we describe methods for identifying
      possible EPCS-associated proteins. These include GFP-tagged protein expression
      followed by image analysis, and immuno-gold labeling at the ultrastructural
      level. In combination, these methods can be used to identify the localization of
      putative EPCS proteins as well as used to postulate their subcellular function.

PMID- 29043668
TI  - Preparation and Imaging of Specialized ER Using Super-Resolution and TEM
      Techniques.
AB  - The plant endoplasmic reticulum (ER) forms several specialized structures. These
      include the sieve element reticulum (SER) and the desmotubule formed as the ER
      passes through plasmodesmata. Imaging both of these structures has been inhibited
      by the resolution limits of light microscopy and their relatively inaccessible
      locations, combined with the fragile nature of the ER. Here we describe methods
      to view desmotubules in live cells under 3D-structured illumination microscopy
      (3D-SIM) and methods to fix and prepare phloem tissue for both 3D-SIM and
      transmission electron microscopy (TEM) which preserve the fragile structure and
      allow the detailed imaging of the SER.

PMID- 29043669
TI  - Quantitation of ER Structure and Function.
AB  - The plant endoplasmic reticulum forms a network of tubules connected by three-way
      junctions or sheet-like cisternae. Although the network is three-dimensional, in
      many plant cells, it is constrained to a thin volume sandwiched between the
      vacuole and plasma membrane, effectively restricting it to a 2-D planar network.
      The structure of the network, and the morphology of the tubules and cisternae can
      be automatically extracted following intensity-independent edge-enhancement and
      various segmentation techniques to give an initial pixel-based skeleton, which is
      then converted to a graph representation. Collectively, this approach yields a
      wealth of quantitative metrics for ER structure and can be used to describe the
      effects of pharmacological treatments or genetic manipulation. The software is
      publicly available.

PMID- 29043670
TI  - Long-Term Imaging of Endoplasmic Reticulum Morphology in Embryos During Seed
      Germination.
AB  - Imaging plant embryos at the cellular level over time is technically challenging,
      since the embryo, once its protective seed coat is removed, must be kept viable
      and unstressed on a microscope slide for the duration of the experiment. Here we
      describe a procedure and suitable apparatus for the visualization, over several
      days, of changes in endoplasmic reticulum (ER) morphology associated with the
      process of germination in Arabidopsis thaliana seeds. Moreover, we also present a
      user-friendly image analysis tool which enables subtle perturbations in the ER
      network to be measured.

PMID- 29043671
TI  - Dancing with the Stars: Using Image Analysis to Study the Choreography of the
      Endoplasmic Reticulum and Its Partners and of Movement Within Its Tubules.
AB  - In this chapter, approaches to the image analysis of the choreography of the
      plant endoplasmic reticulum (ER) labeled with fluorescent fusion proteins
      ("stars," if you wish) are presented. The approaches include the analyses of
      those parts of the ER that are attached through membrane contact sites to moving
      or nonmoving partners (other "stars"). Image analysis is also used to understand
      the nature of the tubular polygonal network, the hallmark of this organelle, and
      how the polygons change over time due to tubule sliding or motion. Furthermore,
      the remodeling polygons of the ER interact with regions of fundamentally
      different topology, the ER cisternae, and image analysis can be used to separate
      the tubules from the cisternae. ER cisternae, like polygons and tubules, can be
      motile or stationary. To study which parts are attached to nonmoving partners,
      such as domains of the ER that form membrane contact sites with the plasma
      membrane/cell wall, an image analysis approach called persistency mapping has
      been used. To study the domains of the ER that are moving rapidly and streaming
      through the cell, the image analysis of optic flow has been used. However, optic
      flow approaches confuse the movement of the ER itself with the movement of
      proteins within the ER. As an overall measure of ER dynamics, optic flow
      approaches are of value, but their limitation as to what exactly is "flowing"
      needs to be specified. Finally, there are important imaging approaches that
      directly address the movement of fluorescent proteins within the ER lumen or in
      the membrane of the ER. Of these, fluorescence recovery after photobleaching
      (FRAP), inverse FRAP (iFRAP), and single particle tracking approaches are
      described.

PMID- 29043672
TI  - Preparation of Highly Enriched ER Membranes Using Free-Flow Electrophoresis.
AB  - Free-flow electrophoresis (FFE) is a technique for separation of proteins,
      peptides, organelles, and cells. With zone electrophoresis (ZE-FFE), organelles
      are separated according to surface charge. The ER is the only remaining major
      cellular compartment in Arabidopsis not to have been isolated using density
      centrifugation, immune-isolation, or any other method previously applied to
      purification of plant membranes. By using continuous-flow electrophoresis ER
      vesicles of similar surface charge, which may have been fragmented during cell
      lysis, can be focused. A large portion of these vesicles are of sufficiently
      different surface charge that separation from the majority of Golgi and other
      contaminants is possible. Here we adapt an earlier ZE-FFE Golgi isolation
      protocol for the isolation of highly pure ER vesicles and for tracking the
      migration of peripheral ER vesicles. Isolating ER vesicles of homogenous surface
      charge allows multi-'omic analyses to be performed on the ER. This facilitates
      investigations into structure-function relationships within the ER.

PMID- 29043673
TI  - ER Microsome Preparation in Arabidopsis thaliana.
AB  - Microsomes are vesicles derived from the endoplasmic reticulum (ER) when cells
      are broken down in the lab. These microsomes are a valuable tool to study a
      variety of ER functions such as protein and lipid synthesis in vitro.Here we
      describe a protocol to isolate ER-derived microsomes Arabidopsis thaliana
      seedlings and exemplify the use of these purified microsomes in enzyme assays
      with the auxin precursors tryptophan (Trp) or indole-3-pyruvic acid (IPyA) to
      quantify auxin synthetic capacity in microsomal and cytosolic fractions.

PMID- 29043674
TI  - ER Membrane Lipid Composition and Metabolism: Lipidomic Analysis.
AB  - Plant ER membranes are the major site of biosynthesis of several lipid families
      (phospholipids, sphingolipids, neutral lipids such as sterols and
      triacylglycerols). The structural diversity of lipids presents considerable
      challenges to comprehensive lipid analysis. This chapter will briefly review the
      various biosynthetic pathways and will detail several aspects of the lipid
      analysis: lipid extraction, handling, separation, detection, identification, and
      data presentation. The different tools/approaches used for lipid analysis will
      also be discussed in relation to the studies to be carried out on lipid
      metabolism and function.

PMID- 29043675
TI  - 2in1 Vectors Improve In Planta BiFC and FRET Analyses.
AB  - Protein-protein interactions (PPIs) play vital roles in all subcellular processes
      and a number of tools have been developed for their detection and analysis. Each
      method has its unique set of benefits and drawbacks that need to be considered
      prior to their application. In fact, researchers are spoilt for choice when it
      comes to deciding which method to use for the initial detection of a PPI, and
      which to corroborate the findings. With constant improvements in microscope
      development, the possibilities of techniques to study PPIs in vivo, and in real
      time, are continuously enhanced, and expanded. Here, we describe three common
      approaches, their recent improvements incorporating a 2in1-cloning approach, and
      their application in plant cell biology: ratiometric Bimolecular Fluorescence
      Complementation (rBiFC), FRET Acceptor Photobleaching (FRET-AB), and Fluorescent
      Lifetime Imaging (FRET-FLIM), using Nicotiana benthamiana leaves and Arabidopsis
      thaliana cell culture protoplasts as transient expression systems.

PMID- 29043676
TI  - Metabolons on the Plant ER.
AB  - Metabolons are protein complexes that contain all the enzymes necessary for a
      metabolic pathway but also scaffolding proteins. Such a structure allows
      efficient channeling of intermediate metabolites from one active site to the next
      and is highly advantageous for labile or toxic intermediates. Here we describe
      two methods currently used to identify metabolons via protein-protein interaction
      methodology: immunoprecipitations using GFP-Trap(r)_A beads to find novel
      interaction partners and potential metabolon components and FRET-FLIM to test for
      and quantify protein-protein interactions in planta.

PMID- 29043677
TI  - Using Optical Tweezers Combined with Total Internal Reflection Microscopy to
      Study Interactions Between the ER and Golgi in Plant Cells.
AB  - Optical tweezers have been used to trap and micromanipulate several biological
      specimens ranging from DNA, macromolecules, organelles to single celled
      organisms. Using a combination of the refraction and scattering of laser light
      from a focused laser beam, refractile objects are physically captured and can be
      moved within the surrounding media. The technique is routinely used to determine
      biophysical properties such as the forces exerted by motor proteins. Here, we
      describe how optical tweezers combined with total internal reflection
      fluorescence (TIRF) microscopy can be used to assess physical interactions
      between organelles, more specifically the ER and Golgi bodies in plant cells.

PMID- 29043678
TI  - Protein Biosynthesis and Maturation in the ER.
AB  - The endoplasmic reticulum takes care of the folding, assembly, and quality
      control of thousands of proteins destined to the different compartments of the
      endomembrane system, or to be secreted in the apoplast. Here we describe how
      these early events in the life of all these proteins can be followed
      biochemically by using velocity or isopycnic ultracentrifugation, metabolic
      labeling with radioactive amino acids, and immunoprecipitation in various
      conditions.

PMID- 29043679
TI  - ER Membrane Protein Interactions Using the Split-Ubiquitin System (SUS).
AB  - Protein-protein interactions (PPIs) play fundamental roles in all cellular
      processes. Especially membrane proteins facilitate a range of important
      biological functions in stimuli perception, signaling, and transport. Here we
      describe a detailed protocol for the yeast mating-based Split-Ubiquitin System
      (mbSUS) to study PPIs of ER membrane proteins in vivo. In contrast to the
      prominent Yeast Two-Hybrid, mbSUS enables analysis of full-length membrane
      proteins in their native cellular context. The system is based on the ubiquitin
      proteasome pathway leading to the release of an artificial transcription factor
      followed by activation of reporter genes to visualize PPIs. The mating-based
      approach is suitable for both small- and large-scale interaction studies.
      Additionally, we describe protocols to apply the recently established SUS Bridge
      assay (SUB) which is optimized for the detection of ternary protein interactions.

PMID- 29043680
TI  - Analysis of Protein Glycosylation in the ER.
AB  - Protein N-glycosylation is an essential posttranslational modification which is
      initiated in the endoplasmic reticulum. In plants, the N-glycans play a pivotal
      role for protein folding and quality control. Through the interaction of glycan
      processing and binding reactions mediated by ER-resident glycosidases and
      specific carbohydrate binding proteins, the N-glycans contribute to the adoption
      of a native protein conformation. Properly folded glycoproteins are released from
      these processes and allowed to continue their transit to the Golgi where further
      processing and maturation of N-glycans leads to the formation of more complex
      structures with different functions. Incompletely folded glycoproteins are
      removed from the ER by a highly conserved degradation process to prevent the
      accumulation or secretion of misfolded proteins and maintain ER homeostasis.
      Here, we describe methods to analyze the N-glycosylation status and the glycan
      dependent ER-associated degradation process in plants.

PMID- 29043681
TI  - The Unfolded Protein Response.
AB  - Under the unfolded protein response (UPR), transcripts encoding the endoplasmic
      reticulum (ER) chaperones are increased and those encoding proteins synthesized
      in the ER are decreased. To reproducibly detect such changes of an expression
      profile, homogeneous growth of plants is desired. In addition, uniform treatment
      with drugs inducing the UPR is also necessary. Here we describe our methods of
      plant culture and drug treatment, and procedure to detect gene expression by
      quantitative RT-PCR.

PMID- 29043682
TI  - Unfolded Protein Response in Arabidopsis.
AB  - The unfolded protein response (UPR) is a highly regulated signaling pathway that
      is largely conserved across eukaryotes. It is essential for cell homeostasis
      under environmental and physiological conditions that perturb the protein folding
      in the endoplasmic reticulum (ER). Arabidopsis is one of the outstanding
      multicellular model systems in which to investigate the UPR. Here, we described a
      protocol to induce the UPR in plants, specifically arabidopsis, and to estimate
      their ability to cope with ER stress through the quantification of physiological
      parameters.

PMID- 29043683
TI  - Fluorescence Imaging of Autophagy-Mediated ER-to-Vacuole Trafficking in Plants.
AB  - Macroautophagy (hereafter referred to as autophagy) is a conserved mechanism in
      eukaryotic cells that delivers unneeded cellular components for degradation in
      the lytic organelle. In plants, as in other eukaryotes, autophagy begins in the
      formation of cup-shaped double membranes that engulf cytosolic material. The
      double membrane closes to form autophagosomes that are then transported to the
      vacuole for degradation. Autophagy can function as a bulk nonselective process or
      as a selective process targeting specific proteins, protein aggregates,
      organelles, or other cellular components for degradation. The endoplasmic
      reticulum (ER) is linked to autophagy-related processes in multiple ways. The ER
      was suggested as a possible site for the nucleation of autophagosomes, and as a
      source for autophagosomal membranes. Furthermore, autophagy has an important role
      in ER homeostasis, and the ER is a target for a selective type of autophagy, ER
      phagy, in response to ER stress. However, the detailed molecular mechanisms,
      especially in plants, are only now starting to be revealed.In this chapter, we
      describe the use of confocal imaging to follow the delivery of fluorescently
      tagged ER-associated proteins to the vacuole. We also describe the utilization of
      fluorescent protein fusions to look at the co-localization of a protein of
      interest with the autophagosome marker protein ATG8, a core autophagy machinery
      protein that is essential for selective autophagy processes.

PMID- 29043684
TI  - Imaging the ER and Endomembrane System in Cereal Endosperm.
AB  - The cereal endosperm is a complex structure comprising distinct cell types,
      characterized by specialized organelles for the accumulation of storage proteins.
      Protein trafficking in these cells is complicated by the presence of several
      different storage organelles including protein bodies (PBs) derived from the
      endoplasmic reticulum (ER) and dynamic protein storage vacuoles (PSVs). In
      addition, trafficking may follow a number of different routes depending on
      developmental stage, showing that the endomembrane system is capable of massive
      reorganization. Thus, developmental sequences involve progressive changes of the
      endomembrane system of endosperm tissue and are characterized by a high
      structural plasticity and endosomal activity.Given the technical dexterity
      required to access endosperm tissue and study subcellular structures and (seed
      storage protein) SSP trafficking in cereal seeds, static images are the state of
      the art providing a bulk of information concerning the cellular composition of
      seed tissue. In view of the highly dynamic endomembrane system in cereal
      endosperm cells, it is reasonable to expect that live cell imaging will help to
      characterize the spatial and temporal changes of the system. The high resolution
      achieved with electron microscopy perfectly complements the live cell imaging.We
      therefore established an imaging platform for TEM as well as for live cell
      imaging. Here, we describe the preparation of different cereal seed tissues for
      live cell imaging concomitant with immunolocalization studies and ultrastructure.

PMID- 29043685
TI  - Abstracts from the 21st Annual Meeting of the European Council for Cardiovascular
      Research (ECCR), Lake Garda, 20-22 October 2017.

PMID- 29043686
TI  - [Lies, damn lies and statistics].
AB  - With this article, we want to emphasize the limits of statistics with little
      samples, a condition very common in our speciality, focusing in the most usual
      mistakes in the interpretation of the p-value. Finally, as conclusion, we
      simulate a clinical study to look what may be a more apropiate boarding.

PMID- 29043687
TI  - [Pleural cavity concerns].
AB  - INTRODUCTION: Persistent air leak (PAL) is a common problem. We asses our
      experience in the management of these patients. MATERIAL AND METHODS:
      Retrospective review of patients with chest tubes after bronchopulmonary
      pneumothorax (due to lung resections, spontaneous pneumothorax, necrotizing
      pneumonia) from 2010 to 2015. We studied clinical data, PAL incidence, risk
      factors and treatment, considering PAL >= 5 days. RESULTS: Thirty-seven cases (28
      patients) between 0-16years: 26 lung resections, 11 pneumothorax. We found no
      differences in the distribution of age, weight, indication or comorbidity, but we
      noticed a trend to shorter hospital stay in infants. Patients with staple-line
      reinforcement presented lower PAL incidence than patients with no mechanical
      suture (43% vs 37%), the difference is even apparent when applying tissue
      sealants (29% vs 50%) (p > 0.05). We encountered no relationship between the size
      of the tube (10-24 Fr) or the type of resection, with bigger air leaks the higher
      suction pressure. We performed 13 pleurodesis in 7 patients (2 lobectomies, 3
      segmentectomies and 2 bronchopleural fistulas), with 70% effectiveness. We
      conducted 7 procedures with autologous blood (1.6 ml/kg), 2 with povidone-iodine
      (0.5 ml/kg), 2 mechanical thoracoscopic and 2 open ones. We repeated pleurodesis
      four times, 3 of them after autologous blood infusion: 2 infusions with the same
      dose (both effective) and the other 2 as thoracotomy in patients with
      bronchopleural fistulas. After instillation of blood 3 patients presented with
      fever. After povidone-iodine instillation, the patient suffered from fever and
      rash. CONCLUSIONS: Intraoperative technical aspects are essential to reduce the
      risk of PAL. Autologous blood pleurodesis, single or repeated, is a minimal
      invasive option, very safe and effective to treat the parenchymatous PAL.

PMID- 29043688
TI  - [Correlation between prenatal ultrasound and postnatal diagnosis of birth
      defects].
AB  - OBJECTIVES: To assess the accuracy of prenatal ultrasound diagnosis and to
      analyze the protocol applied for congenital defects (CD) in our environment.
      METHODS: Descriptive study of prenatally diagnosed CD in our area between 2004
      2013. Includes: total births, fetal medicine referrals (number of consultations,
      ultrasound, invasive techniques) anatomical and chromosomal abnormalities,
      confirmed diagnoses, necropsies performed, false diagnoses, absence of prenatal
      diagnoses, and number and reasons for abortions (VIEs). RESULTS: Mean annual
      births were 3,646 +/- 1,299, with a mean prenatal ultrasound of 2,144 +/- 307 and
      512 +/- 74 invasive techniques per year. The annual average of prenatal
      chromosomopathies diagnosed were 26 +/- 8 and 140 +/- 14 anatomical
      abnormalities, which represents a 36.44% from all of the prenatal ultrasound
      performed. These include: neurological, cardiac and nephron-urological anatomic
      anomalies. Pre and post-natal correlation was observed in 95.6% of the DCs
      detected. Most common causes of abortion were chromosomal abnormalities, heart
      and neurological diseases. CONCLUSIONS: Due to the variety of CD that cause VIEs,
      a highly specialized multidisciplinary approach is recommended to ensure optimal
      information for parents.

PMID- 29043689
TI  - [Mesenteric edema as a prenatal ultrasound sign of poor prognosis in
      gastroschisis].
AB  - INTRODUCTION/AIM OF THE STUDY: Gastroschisis is a congenital malformation with an
      easy and early prenatal diagnosis, however, it has a variable post-natal outcome.
      Our aim was to determine if certain ultrasound markers or early delivery were
      related with a worse postnatal outcome. PATIENTS AND METHODS: Retrospective study
      of a cohort of patients with gastroschisis diagnosed between 2005-2014, with
      emphasis on prenatal ultrasounds, gestational age at delivery and post-natal
      outcome. Oligohydramnios, peel, mesenteric edema, fixed and dilated bowel with
      loss of peristalsis and small wall defect were considered ultrasonographic
      markers associated with poor prognosis. Outcome variables included: length-of
      stay, complications, nutritional and respiratory factors. Non-parametric
      statistical analysis were used with p < 0,05 regarded as significant. RESULTS:
      Clinical charts of 30 patients with gastroschisis were reviewed (17M/13F).
      Gestational age at diagnosis was 20 (12-31) and at delivery 36 (31-39) weeks (33%
      of the patients over 36+3 weeks). A 73% of the patients presented at least one
      ultrasonographic marker factor during follow-up. Univariate analysis showed that
      mesenteric edema was associated with poor outcome variables: short-bowel syndrome
      (p= 0,000), PN-dependence (p= 0,007) and intestinal atresia (p= 0,02). The
      remaining risk factors analysed, including late delivery (> 36+3 weeks) were not
      associated with length-of-stay, ventilatory support, digestive autonomy,
      complications or mortality. CONCLUSIONS: Neither the presence of ultrasonographic
      markers classically associated with unfavorable outcomes, nor early delivery (<
      36 weeks) resulted in worse postnatal outcome. Mesenteric edema was the only
      alarming ultrasound marker and that may suggest the need of closer follow-up.

PMID- 29043690
TI  - [Prevention of the wound infection: little changes, huge results].
AB  - INTRODUCTION: Neonatal surgical wound infection occurs in almost 50% of neonatal
      procedures. It increases the rates of morbimortality in neonatal units. There is
      no guidelines about prevention of wound infection in neonatal surgery. We present
      our results after changing our behaviour in neonatal surgery. MATERIALS AND
      METHODS: Comparative study between 2 groups. In order to decrease wound infection
      at the end of the procedure gloves, covertures and surgical instruments were
      changed and saline and antiseptic solutions were used during laparotomy closing.
      Group P included procedures with these recommendations and Group NP without them.
      Age, weight, surgery, infection, length of stay, and mortality were analized
      between groups through a logistic regression model. RESULTS: Group P included 55
      procedures in 32 patients, median weight 1,300 g (1,000-2,100), 19 median days of
      life (6-40), 5 postoperative wound problems (9%). Group NP included 26 procedures
      in 14 neonates, median weight 1,700 g (700-2,500), 20 median days of life (3-33),
      14 wound problems (53.8%). We decrease the wound problems in our patients in
      44.8% (p < 0.0001). Additionally, the protection provided by our recommendations
      was maintained after adjustment by weight, age and type of pathology (0.07) p=
      0.000. CONCLUSIONS: Simple changes in during the procedures in neonatal surgery
      can reduce the appearance of wound infection and morbidity.

PMID- 29043691
TI  - [Analysis of hypertrophic pyloric stenosis: size does matter].
AB  - OBJECTIVES: To analyze the correlation between pyloric size and evolution of
      patients surgically treated for infantile hypertrophic pyloric stenosis (IHPS).
      PATIENTS AND METHODS: We realized a retrospective study of 109 patients
      undergoing IHPS in 5 years. We analyzed by chi2 test if a correlation between
      evolution time, age and postoperative vomiting and gastroesophageal reflux
      disease (GERD), and pyloric muscle thickness (group A > 4.5 mm and group B <= 4.5
      mm) and pyloric channel length (group A >= 20 mm and group B < 20 mm) exists.
      RESULTS: There is a statistically significant correlation between longer
      evolution history (>48 h) and pyloric length >= 20 mm and between age (> 30 days)
      and muscle thickness > 4.5 mm (p= 0.022 and p= 0.009, respectively). Also, 38.5%
      of 109 patients had postoperative emesis 2 days after surgery and 13.8% had GERD
      for a median time of 8.27 months (1-12 months), showing that there is a
      statistically significant correlation (p= 0.007) between pyloric channel length
      >= 20 mm and postoperative emesis. It was not observed correlation between
      pyloric thickness and length and GERD. CONCLUSIONS: It has been observed that
      there is correlation between pyloric length >= 20 mm and postoperative emesis.
      However, it has not been observed regarding the pyloric muscle thickness. A
      longer preoperative evolution and age > 30 days are correlated to channel length
      >= 20 mm and muscle thickness > 4.5 mm, respectively.

PMID- 29043692
TI  - [Appendicitis versus nonspecific acute abdominal pain: diagnostic accuracy of
      ultrasound].
AB  - PURPOUSE: The aim of this study is to assess the diagnostic accuracy of
      ultrasound to differentiate appendicitis from nonspecific acute abdominal pain,
      that is the most common process requiring differential diagnosis in clinical
      practice. MATERIAL AND METHODS: Patients admitted for suspicion of appendicitis
      were prospectively evaluated in our hospital during two years (2013-2014). Cases
      of nonspecific acute abdominal pain and appendicitis assessed by ultrasound were
      enrolled in the study. The different variables collected were statistically
      analyzed by descriptive, univariate and diagnostic accuracy studies. RESULTS: A
      total of 275 patients were studied, 143 cases of nonspecific acute abdominal pain
      and 132 cases of appendicitis. Ultrasound sensitivity and specificity to
      differentiate appendicitis were 94.7% and 87.4% respectively, with a 12.6% rate
      of false positives and a 5.3% rate of false negatives. The rate of false
      negatives in perforated group was 17.4% and analysis according to Pediatric
      Appendicitis Score risk groups showed a 12.2% rate of false positives in low-risk
      group and a 6.3% rate of false negatives in high-risk group. CONCLUSIONS: The use
      of ultrasound in low clinical probability cases of appendicitis could rise
      unnecessary surgery rate, due to the significant number of false positives in
      this group of patients. In high probability clinical cases, ultrasound does not
      contribute too much to diagnosis and it could be a confusion factor by the
      significant number of false negative associated to perforated appendicitis.

PMID- 29043693
TI  - [Post-appendectomy intra-abdominal abscesses: six years' experience in a
      Pediatric Surgery Department].
AB  - OBJECTIVES: Post-appendectomy intra-abdominal abscesses are estimated to
      complicate up to 4.2% of acute non-perforated appendicitis and between 6.7% and
      28% acute perforated appendicitis. This study was performed with the aim to
      review and characterize post-appendectomy intra-abdominal abscesses in our
      Pediatric Surgery department; to calculate their incidence and to evaluate the
      efficacy of the treatment modality. MATERIAL AND METHODS: A retrospective
      analysis of all patients, under 18 years and with the diagnosis of intra
      abdominal abscess post-appendectomy, between January 2010 and December 2015 was
      performed, taking in account initial surgical approach, type of acute
      appendicitis, length of hospital stay and the treatment applied. Data were
      collected by reviewing clinical files. RESULTS: In a total of 1,340
      appendectomies performed, there were 24 intra-abdominal abscesses identified
      (1.79%). Eight were feminine and sixteen masculine, and mean age was 11.9 years.
      In 52% of cases the diagnosis was made in the initial admission. Twelve have been
      submitted to laparoscopic appendectomy and the other 12 to open appendectomy. Of
      the 24 patients, only 4 needed a surgical re-intervention, which leaves medical
      treatment an 83.3% success rate. CONCLUSIONS: TThe incidence of intra-abdominal
      abscesses post-appendectomy, in the studied population, is what was expected and
      inferior to what's described in the literature. In our sample, conservative
      management for intra-abdominal abscesses post-appendectomy was successful in most
      of the cases, only 4 needing further surgical intervention.

PMID- 29043694
TI  - [Long-term results of hypospadias surgery. Urinary and sexual function, and
      psychological impact].
AB  - OBJECTIVES: To determine the current status of the patients operated on for
      hypospadias in our region, in order to adapt the surgical technique to their real
      needs. MATERIAL AND METHODS: A descriptive and observational study. Interviews
      were conducted with hypospadias surgery patients in our hospital between 1976 and
      1996, focusing on their urinary and sexual function and psychological impact. We
      performed a descriptive statistical analysis and comparisons between types of
      hypospadias (SPSSv19). RESULTS: 566 patients were operated on for hypospadias
      during the study period, interviewing 100 aged between 18 and 40 years. The 73%
      were distal and 27% proximal. Of all patients, 30% do not have an orthotopic
      meatus, 10% have fistula, 18% have some degree of stenosis and 52% have penile
      curvature. The 13% feel to have had disadvantages in their life. They consider
      they have a different penis in: size (19%), glans shape (17%), curvature (14%),
      scars (10%) and lowest hole (7%). Sexual satisfaction was valued at 8.9 on a
      scale of 1 to 10, with no differences between the types of hypospadias. Proximal
      hypospadias patients have more ejaculation problems: 42% versus 11% in distal
      hypospadias. The 68% of the proximal ones would like to improve compared to 20%
      of the distal in: appearance (17%), size (11%) and way to urinate (11%).
      CONCLUSIONS: Anatomic abnormalities are maintained but the aspects that values
      the adult patient differ from those persecuted by practiced surgeries. A
      significant percentage of patients would try to get another surgery. Keeping the
      size of the penis and natural appearance of the glans should be a priority in
      hypospadias surgery.

PMID- 29043695
TI  - [Vascular anomalies in the neonatal period].
AB  - OBJECTIVE: Vascular anomalies in the neonatal period are a diagnostic challenge
      for the lack of evident signs, symptoms and follow-up, and the convenience of
      restricting aggressive diagnostic tests. The aim of this work is to review the
      characteristics of neonatal cases presented to our Vascular Anomalies Unit in the
      last 5 years. MATERIALS AND METHODS: All cases of suspected vascular anomaly
      presented to our unit before 1 month of age between 2010 and 2015 were reviewed,
      diagnostic tests and treatments carried out with chronology were analyzed.
      Presumptive diagnosis and final diagnosis (when available) were compared.
      RESULTS: Fifteen vascular tumors were found, 2 with visceral involvement: 6
      infantile hemangiomas (IH), 3 NICH, 4 RICH, 1 tufted hemangioma, 1 unspecified
      liver vascular tumor, 3 venous malformations (2 equivocal MRI and a
      hyperkeratotic venous malformation), 4 lymphatic malformations, 3 of them
      macrocystic, and 2 vascular lesions that were diagnosed of fibrosarcoma and
      sclerema neonatorum and they were not vascular anomalies. Only 3 patients with
      macrocystic lymphatic malformations had prenatal diagnosis. CONCLUSION: Accurate
      diagnosis of vascular anomalies during the first month of life is difficult, even
      with MRI. Only in a few cases early treatment is needed, so it is worth taking
      time to follow-up. Different types of treatment (observation, propranolol,
      biopsy, laser, embolization, and resection) will depend on the condition to be
      treated. A continuous observation can avoid unnecessary procedures and risks.

PMID- 29043696
TI  - [Complete and inverted esophagastric duplicity].
AB  - CASE REPORT: A 4-month old girl affected by gastric duplication discovered as a
      palpable abdominal mass displacing the spleen and left kidney. During laparotomy,
      a yellowish secretion is aspirated and the gastric duplication is excised
      together with the common muscular Wall of the greater curvature of the stomach.
      Also excised, a tubular structure starting from the inferior pole of the
      malformation, and communicating with it, passing superior to the head of the
      pancreas and the second portion of the duodenum, followed by a posterior course
      before inserting into the right cruz of the diaphragm. The histology of the
      tubular formation was compatible with esophagus. CONCLUSION: This type of
      duplication has not been reported in the literature and reinforces the theory
      that these malformations could be secondary to genetic transcription errors, in
      the differentiation of the endoderm of the primitive digestive tract and the
      notochord.

PMID- 29043697
TI  - Revisiting The Relationship between The Ejaculatory Abstinence Period and Semen
      Characteristics.
AB  - Variation in the ejaculatory abstinence period suggested by different guidance
      bodies have resulted in a growing concern among researchers and clinicians over
      what the precise period of ejaculatory abstinence ought to be for an optimal
      semen sample. Several studies have thus been undertaken to examine the
      association between the length of sexual abstinence and semen characteristics.
      Not all studies, however, have arrived at the same conclusions. This study aims
      to review all existing literature published during the past few decades
      pertaining to the influence of ejaculatory abstinence on semen quality. For the
      purpose of this systematic review, all data related to sexual abstinence duration
      and seminal parameters were re-analysed to homogenize the current data. Thorough
      PubMed, MEDLINE and Google Scholar, a literature search was conducted using the
      keywords "sexual abstinence", "ejaculatory abstinence", "semen", "spermatozoa",
      "semen analysis", "sperm parameters", "motility", "reactive oxygen species (ROS)"
      and "DNA fragmentation". After carefully reviewing all the literature, 30
      relevant papers, both written in English and published between January 1979 and
      December 2016, were included in this review. The weight of the evidence suggests
      that the decline in semen volume and sperm concentration with shorter abstinence
      periods is accompanied by a substantial improvement in sperm motility
      characteristics, especially progressive motility and velocity. Nevertheless,
      available data are insufficient to support definitive conclusions regarding the
      influence of the ejaculatory abstinence period on advanced semen parameters (ROS,
      DNA fragmentation and seminal plasma antioxidant capacity) and pregnancy rates.
      In conclusion, taking all data into account, shortening of the abstinence period
      may be beneficial to sperm quality. Furthermore, we recommend that the current
      guidelines regarding the prescribed abstinence period should be revisited.

PMID- 29043698
TI  - Gene Polymorphism of Matrix Metalloproteinase 9 in Asthenozoospermic Male
      Subjects.
AB  - Background: Matrix metalloproteinase (MMPs) play important roles in the
      structural and functional properties of reproductive organs. The aim of this
      study is to determine the prevalence of C-1562T MMP-9 (rs3918242) gene
      polymorphism in fertile and infertile men. In addition, we aim to determine the
      association between C-1562T MMP-9 and G-1575A MMP-2 gene polymorphisms. MATERIALS
      AND METHODS: A total of 400 subjects, including 200 fertile and 200 infertile
      men, were recruited for this casecontrol study. The allele frequencies and
      genotype distributions of single nucleotide polymorphism in the promoter regions
      of MMP-9 (C-1562T) were determined using polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) analysis. The chi-square (chi2) test was
      used to assess the distribution of genotype frequencies. RESULTS: There were no
      significant differences found in the genotype distributions or allele frequencies
      between fertile and infertile men for the C-1562T MMP-9 gene polymorphism. The
      percent of immotile sperm in infertile men with the CC and CT genotypes of C
      1562T MMP-9 gene polymorphism significantly differed compared with that of
      subjects with the TT genotype. The frequency of CC/GA-combined genotypes of C
      1562T MMP-9 and G-1575A MMP-2 gene polymorphisms significantly differed in
      fertile and infertile men (P=0.031). CONCLUSION: Our results suggest that genetic
      polymorphisms in MMP may impact male fertility.

PMID- 29043699
TI  - Multiplex-Polymerase Chain Reaction for Detecting Microdeletions in The
      Azoospermia Factor Region of Y Chromosome in Iranian Couples with Non-Obstructive
      Infertility and Recurrent Pregnancy Loss.
AB  - Background: Approximately 15% of couples are infertile with the male factor
      explaining approximately 50% of the cases. One of the main genetic factors
      playing a role in male infertility is Y chromosomal microdeletions within the
      proximal long arm of the Y chromosome (Yq11), named the azoospermia factor (AZF)
      region. Recent studies have shown there is a potential connection between
      deletions of the AZF region and recurrent pregnancy loss (RPL). The aim of this
      study is to examine this association by characterizing AZF microdeletions in two
      infertile groups: in men with non-obstructive infertility and in men with wives
      displaying RPL. MATERIALS AND METHODS: In this is a case-control study, genomic
      DNA was extracted from 80 male samples including 40 non-obstructive infertile
      men, 20 males from couples with RPL and 20 fertile males as controls. Multiplex
      polymerase chain reaction was used to amplify 19 sequence tagged sites (STS) to
      detect AZF microdeletions. Differences between the case and control groups were
      evaluated by two-tailed unpaired t test. P<0.05 were considered statistically
      significant. RESULTS: Only one subject was detected to have Y chromosome
      microdeletions in SY254, SY157 and SY255 among the 40 men with non-obstructive
      infertility. No microdeletion was detected in the males with wives displaying RPL
      and in 20 control males. Y chromosome microdeletion was neither significantly
      associated with non-obstructive infertility (P=0.48) nor with recurrent pregnancy
      loss. CONCLUSION: Performing Testing for Y chromosome microdeletions in men with
      non-obstructive infertility and couples with RPL remains inconclusive in this
      study.

PMID- 29043700
TI  - Body Mass Index Effects Kruger's Criteria in Infertile Men.
AB  - Background: The aim of this study is to evaluate the relationship between sperm
      parameters and body mass index (BMI) in the male spouses with infertility
      complaints, who had reffered to our clinic. MATERIALS AND METHODS: The male
      spouses from 159 couples reffering to our clinic because of infertility, during a
      six-month period, were included in the study. In this prospective case control
      study, the included men were categorized as non-obese (BMIP<25 kg/m2), overweight
      (BMI 25-29 kg/m2) and obese (BMI >=30 kg/m2) according to their BMIs. The
      assessed sperm parameters consisted of; sperm concentration, Kruger morphology,
      progressive motility level, and volume pH levels. The statistical significant
      level was set as less than 0.05. RESULTS: The assessed group consisted of 159
      patients applying to our clinic with infertility symptoms. Fifty-three non-obese,
      53 overweight and 53 obese men were eligible for the study. There was
      statistically significant differences in sperm volume (P<0.001), progressive
      motility (P<0.001), postwash sperm count (P<0.001) and Kruger (P<0.001)
      morphology among the patient groups grouping according to the BMI levels.
      CONCLUSION: In this study, increased BMI was associated with decreased semen
      quality, affecting volume, concentration, and motility. further studies with a
      wider range of prospective cases need to be conducted in order to investigate the
      effects on male fertility in more detail.

PMID- 29043701
TI  - Royal Jelly Promotes Ovarian Follicles Growth and Increases Steroid Hormones in
      Immature Rats.
AB  - Background: Royal jelly (RJ) is a complementary diet widely prescribed by
      traditional medicine specialists for treatment of infertility. The aim of present
      study was to evaluate the effects of RJ on a set of reproductive parameters in
      immature female rats. MATERIALS AND METHODS: In this experimental study, thirty
      two immature female rats (30-35 g) were divided into four groups (n=8/group):
      three experimental groups and one control. The experimental groups received 100,
      200 and 400 mg/kg/body weight doses of RJ daily for 14 days, and the control
      group received 0.5 ml distilled water interaperitonealy (i.p). The treated rats
      were sacrificed and their ovaries were dissected for histological examination.
      The serum levels of ovarian hormones, nitric oxide (NO) and ferric reducing
      antioxidant power (FRAP) were evaluated, and the ratios of the ovarian and
      uterine weight to body weight were calculated. One-way ANOVA was used for data
      analysis. RESULTS: The body weights were significantly different (P=0.002) among
      the rat groups, with an increase in all RJ treated animals. Uterine and ovarian
      weights and the serum levels of progesterone (P=0.013) and estradiol (P=0.004)
      were significantly increased in experimental groups compared to the control
      group. In addition, a significant increase in the number of mature follicles and
      corpora lutea (P=0.007) was seen in RJ recipients compared to the controls. A
      significant increase in the serum levels of FRAP (P=0.009) and a significant
      decrease in NO level (P=0.013) were also observed. CONCLUSION: RJ promotes
      folliculogensis and increases ovarian hormones. This product can be considered as
      a natural growth stimulator for immature female animals.

PMID- 29043702
TI  - N-Acetylcysteine Compared to Metformin, Improves The Expression Profile of Growth
      Differentiation Factor-9 and Receptor Tyrosine Kinase c-Kit in The Oocytes of
      Patients with Polycystic Ovarian Syndrome.
AB  - Background: Paracrine disruption of growth factors in women with polycystic
      ovarian syndrome (PCOS) results in production of low quality oocyte, especially
      following ovulation induction. The aim of this study was to investigate the
      effects of metformin (MET), N-acetylcysteine (NAC) and their combination on the
      hormonal levels and expression profile of GDF-9, BMP-15 and c-kit, as hallmarks
      of oocyte quality, in PCOS patients. MATERIALS AND METHODS: This prospective
      randomized, double-blind, placebo controlled trial aims to study the effects of
      MET, NAC and their combination (MET+NAC) on expression of GDF-9, BMP-15 and c-kit
      mRNA in oocytes [10 at the germinal vesicle (GV) stage, 10 at the MI stage, and
      10 at the MII stage from per group] derived following ovulation induction in
      PCOS. Treatment was carried out for six weeks, starting on the third day of
      previous cycle until oocyte aspiration. The expression of GDF9, BMP15 and c-kit
      were determined by quantitative real time polymerase chain reaction (RT-qPCR) and
      western blot analysis. Data were analyzed with one-way ANOVA. RESULTS: The
      follicular fluid (FF) level of c-kit protein significantly decreased in the NAC
      group compared to the other groups. Significant correlations were observed
      between the FF soluble c-kit protein with FF volume, androstenedione and
      estradiol. The GDF-9 expression in unfertilized mature oocytes were significantly
      higher in the NAC group compared to the other groups (P<0.001). Similar
      difference was not observed between the MET, NAC+MET and control groups. The c
      kit expression in unfertilized mature oocytes were significantly lower in the NAC
      group compared to the other groups (P<0.001). Similar difference was not observed
      between the MET, NAC+MET and control groups (Registration number:
      IRCT201204159476N1). CONCLUSION: We concluded that NAC can improve the quality of
      oocytes in PCOS.

PMID- 29043703
TI  - The Effects of Dienogest on Macrophage and Natural Killer Cells in Adenomyosis: A
      Randomized Controlled Study.
AB  - Background: Progestin has been used for symptomatic treatment of adenomyosis,
      although its effect on the immune system has not been studied. The aim of this
      study was to investigate the changes of macrophage and natural killer (NK) cell
      infiltration in tissues obtained from women with adenomyosis who did or did not
      receive oral progestin dienogest. MATERIALS AND METHODS: In this randomized
      controlled clinical trial study, 24 patients with adenomyosis who required
      hysterectomy were enrolled. Twelve patients received dienogest 28-35 days before
      surgery, and the other 12 patients were not treated with any hormones. The
      endometrial and myometrial tissue samples were immediately collected after
      hysterectomy, and immunohistochemistry for a macrophage marker (CD68) and a NK
      cells marker (CD57) was performed. RESULTS: The number of CD57 cells was
      significantly increased in endometrial glands of the treated group compared to
      the untreated group (P=0.005) but not in stroma in the endometrium of the treated
      patients (P=0.416). The difference in the number of CD68 cells was not
      statistically significant between treated and untreated groups in the endometrial
      glands (P=0.055) or stromal tissues (P=0.506). CONCLUSION: Administration of oral
      progestin dienogest to patients with adenomyosis increased the number of uterine
      infiltrating NK cells in glandular structure of eutopic endometrium. The
      differential effects of progestin on NK cells depended on the site of immune cell
      infiltration. The effects of oral progestin on uterine NK cells in adenomyosis
      have the potentials to be beneficial to pregnancies occurring following
      discontinuation of treatment in terms of embryo implantation and fetal protection
      (Registration number: TCTR20150921001).

PMID- 29043704
TI  - Accuracy of Two-Dimensional Transvaginal Sonography and Office Hysteroscopy for
      Detection of Uterine Abnormalities in Patients with Repeated Implantation
      Failures or Recurrent Pregnancy Loss.
AB  - Background: We sought to compare diagnostic values of two-dimensional
      transvaginal sonography (2D TVS) and office hysteroscopy (OH) for evaluation of
      endometrial pathologies in cases with repeated implantation failure (RIF) or
      recurrent pregnancy loss (RPL). MATERIALS AND METHODS: This prospective study was
      performed at Royan Institute from December 2013 to January 2015. TVS was
      performed before hysteroscopy as part of the routine diagnostic work-up in 789
      patients with RIF or RPL. Uterine biopsy was performed in cases with abnormal
      diagnosis in TVS and/or hysteroscopy. We compared the diagnostic accuracy values
      of TVS in detection of uterine abnormalities with OH by receiver operating
      characteristic (ROC) curve analysis. RESULTS: TVS examination detected 545 (69%)
      normal cases and 244 (31%) pathologic cases, which included 84 (10.6%)
      endometrial polyps, 15 (1.6%) uterine fibroids, 10 (1.3%) Asherman's syndrome, 9
      (1.1%) endometrial hypertrophy, and 126 (15.9%) septate and arcuate uterus. TVS
      and OH concurred in 163 pathologic cases, although TVS did not detect some
      pathology cases (n=120). OH had 94% sensitivity, 95% specificity, 62% positive
      predictive value (PPV), and 99% negative predictive value (NPV) for detection of
      endometrial polyps. In the diagnosis of myoma, sensitivity, specificity, PPV, and
      NPV were 100%. TVS had a sensitivity of 50% and specificity of 98% for the
      diagnosis of myoma. For polyps, TVS had a sensitivity of 54% and specificity of
      80%. Area under the ROC curve (AUROC) was 70.69% for the accuracy of TVS compared
      to OH. CONCLUSION: TVS had high specificity and low sensitivity for detection of
      uterine pathologies in patients with RIF or RPL compared with OH. OH should be
      considered as a workup method prior to treatment in patients with normal TVS
      findings.

PMID- 29043705
TI  - Quality of Life and Its Influencing Factors of Couples Referred to An Infertility
      Center in Shiraz, Iran.
AB  - Background: Infertility adversely affects quality of life (QoL). The present
      study aims to evaluate QoL and its associated factors among infertile couples.
      MATERIALS AND METHODS: In this cross-sectional study, the Fertility QoL
      (FertiQoL) instrument was used to measure QoL among 501 volunteer couples who
      attended the Infertility Clinic at the Mother and Child Hospital, Shiraz, Iran.
      We used an additional questionnaire to assess participants' demographic and
      clinical characteristics. The relationship between the scores of QoL to the
      sociodemographic and treatment data was analysed. RESULTS: The subjects with
      lower income levels had lower relational, mind/body, emotional, and total core
      scores. Female participants without academic education had lower scores in the
      emotional subscale, while the male participants showed lower scores in emotional,
      mind/body, relational, social, and total QoL domains. Subjects who had undergone
      any type of treatment, including pharmacological treatment, intrauterine
      insemination (IUI), intra-cytoplasmic sperm injection (ICSI), and in vitro
      fertilization (IVF) showed significantly lower scores in the environmental
      domain. Participants with lower infertility duration obtained significantly
      greater QoL scores. Finally, tolerability, emotional, and environmental domains
      were significantly more desirable when the infertility problem was related to a
      male factor. CONCLUSION: Infertile couples with shorter duration of infertility
      and male etiology have higher QoL. Lower academic education, lower income levels,
      or prior unsuccessful treatments are associated with lower QoL.

PMID- 29043706
TI  - The Effects of Exercise on Expression of CYP19 and StAR mRNA in Steroid-Induced
      Polycystic Ovaries of Female Rats.
AB  - Background: Polycystic ovarian syndrome (PCOS) is the most frequent female
      endocrine disorder that affects 5-10% of women. PCOS is characterized by
      hyperandrogenism, oligo-/anovulation, and polycystic ovaries. The aim of the
      present research is to evaluate the expression of steroidogenic acute regulatory
      protein (StAR) and aromatase (CYP19) mRNA in the ovaries of an estradiol valerate
      (EV)-induced PCOS rat model, and the effect of treadmill and running wheel
      (voluntary) exercise on these parameters. MATERIALS AND METHODS: In this
      experimental study, we divided adult female Wistar rats that weighed
      approximately 220 +/- 20 g initially into control (n=10) and PCOS (n=30).
      Subsequently, PCOS group were divided to PCOS, PCOS with treadmill exercise (P
      ExT), and PCOS with running wheel exercise (P-ExR) groups (n=10 per group). The
      expressions of StAR and CYP19 mRNA in the ovaries were determined by quantitative
      real-time reverse transcriptase polymerase chain reaction (qRT-PCR). Data were
      analyzed by one-way ANOVA using SPSS software, version 16. The data were assessed
      at alpha=0.05. RESULTS: There was significantly lower mRNA expression of CYP19 in
      the EV-induced PCOS, running wheel and treadmill exercise rats compared to the
      control group (P<0.001). Treadmill exercise (P=0.972) and running wheel exercise
      (P=0.839) had no significant effects on CYP19 mRNA expression compared to the
      PCOS group. mRNA expression of StAR in the ovaries of the PCOS group indicated an
      increasing trend compared to the control group, however this was not
      statistically significant (P=0.810). We observed that 8 weeks of running wheel
      and treadmill exercises could not statistically decrease StAR mRNA expression
      compared to the PCOS group (P=0.632). CONCLUSION: EV-induced PCOS in rats
      decreased CYP19 mRNA expression, but had no effect on StAR mRNA expression. We
      demonstrated that running wheel and moderate treadmill exercise could not modify
      CYP19 and StAR mRNA expressions.

PMID- 29043707
TI  - Congenital Malformations in Singleton Infants Conceived by Assisted Reproductive
      Technologies and Singleton Infants by Natural Conception in Tehran, Iran.
AB  - Background: Multiple pregnancies occur more frequently in assisted reproductive
      technology (ART) compared to normal conception (NC). It is known that the risk of
      congenital malformations in a multiple pregnancy are higher than single
      pregnancy. The aim of this study is to compare congenital malformations in
      singleton infants conceived by ART to singleton infants conceived naturally.
      MATERIALS AND METHODS: In this historical cohort study, we performed a historical
      cohort study of major congenital malformations (MCM) in 820 singleton births from
      January 2012 to December 2014. The data for this analysis were derived from
      Tehran's ART linked data file. The risk of congenital malformations was compared
      in 164 ART infants and 656 NC infants. We performed multiple logistic regression
      analyses for the independent association of ART on each outcome. RESULTS: We
      found 40 infants with MCM 29 (4.4%) NC infants and 14 (8.3%) ART infants. In
      comparison with NC infants, ART infants had a significant 2-fold increased risk
      of MCM (P=0.046). After adjusting individually for maternal age, infant gender,
      prior stillbirth, mother's history of spontaneous abortion, and type of delivery,
      we did not find any difference in risk. In this study the majority (95.1%) of all
      infants were normal but 4.9% of infants had at least one MCM. We found a
      difference in risk of MCMs between in vitro fertilization (IVF) and
      intracytoplasmic sperm injection (ICSI). We excluded the possible role of
      genotype and other unknown factors in causing more malformations in ART infants.
      CONCLUSION: This study reported a higher risk of MCMs in ART singleton infants
      than in NC singleton infants. Congenital heart disease, developmental dysplasia
      of the hip (DDH), and urogenital malformations were the most reported major
      malformations in singleton ART infants according to organ and system
      classification.

PMID- 29043708
TI  - Comparison of In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycle
      Outcome in Patients with and without Polycystic Ovary Syndrome: A Modified
      Poisson Regression Model.
AB  - Background: Polycystic ovary syndrome (PCOS) is a frequent condition in
      reproductive age women with a prevalence rate of 5-10%. This study intends to
      determine the relationship between PCOS and the outcome of assisted reproductive
      treatment (ART) in Tehran, Iran. MATERIALS AND METHODS: In this historical cohort
      study, we included 996 infertile women who referred to Royan Institute (Tehran,
      Iran) between January 2012 and December 2013. PCOS, as the main variable, and
      other potential confounder variables were gathered. Modified Poisson Regression
      was used for data analysis. Stata software, version 13 was used for all
      statistical analyses. RESULTS: Unadjusted analysis showed a significantly lower
      risk for failure in PCOS cases compared to cases without PCOS [risk ratio (RR):
      0.79, 95% confidence intervals (CI): 0.66-0.95, P=0.014]. After adjusting for the
      confounder variables, there was no difference between risk of non-pregnancy in
      women with and without PCOS (RR: 0.87, 95% CI: 0.72-1.05, P=0.15). Significant
      predictors of the ART outcome included the treatment protocol type, numbers of
      embryos transferred (grades A and AB), numbers of injected ampules, and age.
      CONCLUSION: The results obtained from this model showed no difference between
      patients with and without PCOS according to the risk for non-pregnancy.
      Therefore, other factors might affect conception in PCOS patients.

PMID- 29043709
TI  - Estimation of Day-Specific Probabilities of Conception during Natural Cycle in
      Women from Babylon.
AB  - Background: Identifying predictors of the probabilities of conception related to
      the timing and frequency of intercourse in the menstrual cycle is essential for
      couples attempting pregnancy, users of natural family planning methods, and
      clinicians diagnosing for possible causes of infertility. The aim of this study
      is to estimate the days in which the likelihood of conception happened by using
      first trimester ultrasound fetal biometry in natural cycles and spontaneous
      pregnancy, and to explore some factors that may affect them. MATERIALS AND
      METHODS: This study is retrospective cohort study, with random sampling. It
      involved 60 pregnant ladies at first trimester; the date of conception was
      estimated using: i. Crown-rump length biometry (routine ultrasound examinations
      were performed at a median of 70 days following Last menstrual period or
      equivalently 10 weeks), ii. Date of last menstrual cycle. Only women with
      previous infertility and now conceiving naturally with a certain date of Last
      menstrual period were selected. RESULTS: The distribution of conception showed a
      sharp rise from day 8 onwards, reaching its maximum at day 13 and decreasing to
      zero by day 30 of Last menstrual period. The older and obese women had conceive
      earlier than younger women but there was insignificants difference between the
      two groups (P>0.05). According to the type of infertility, the women with
      secondary infertility had conceived earlier than those with primary infertility.
      There was a significant difference between the two groups (P<0.05). CONCLUSION:
      Day specific of conception may be affected by factors such as age, BMI, and type
      of infertility. This may be confirmed by larger sample size in metacentric study.

PMID- 29043710
TI  - Pregnancy in Non-Communicating Rudimentary Horn of A Unicornuate Uterus.
AB  - Diagnosis and management of pre-rupture stage of the pregnant horn are difficult
      and usually missed on a routine ultrasound scan. Also most cases are detected
      after rupture of pregnant horn. We presented a 28-year-oldG2 L1 woman with
      diagnosis of rudimentary horn pregnancy (RHP) at 14 weeks of gestation. We
      diagnosed her with a normal intrauterine pregnancy, whereas a pregnancy in a
      right-sided non-communicating rudimentary horn with massive hemoperitoneum was
      later discovered on laparotomy. RHP has a high risk of death for mother, so there
      must be a strong clinical suspicion for the diagnosis of RHP. Although there is a
      major advancement in field of diagnostic ultrasound and other imaging modalities,
      prenatal diagnosis has remained elusive and a laparotomy surgery is considered as
      a definitive diagnosis.

PMID- 29043711
TI  - The Many Guises of Endometriosis: Giant Abdominal Wall Endometriosis Masquerading
      as An Incisional Hernia.
AB  - Endometriosis is defined by the presence of ectopic endometrial tissue outside
      the uterine cavity. Although it is a leading cause of chronic pelvic pain and
      infertility, its clinical presentation can vary, resulting in diagnostic and
      therapeutic challenges. Extrapelvic endometriosis is particularly difficult to
      diagnose owing to its ability to mimic other conditions. Endometrial tissue in a
      surgical scar is uncommon and often misdiagnosed as a granuloma, abscess, or
      malignancy. Cyclical hemorrhagic ascites due to peritoneal endometriosis is
      exceptionally rare. We report the case of a pre-menopausal, nulliparous 44-year
      old woman who presented with ascites and a large abdominal mass that arose from
      the site of a lower midline laparotomy scar. Five years previously, she had
      undergone open myomectomy for uterine fibroids. Soon after her initial operation
      she developed abdominal ascites, which necessitated percutaneous drainage on
      multiple occasions. We performed a laparotomy with excision of the abdominal wall
      mass through an inverted T incision. The extra-abdominal mass consisted of mixed
      cystic and solid components, and weighed 1.52 kg. It communicated with the
      abdominopelvic cavity through a 2 cm defect in the linea alba. The abdomen
      contained a large amount of odourless, brown fluid which drained into the mass.
      There was a large capsule that covered the small and large bowel, liver,
      gallbladder, and stomach. Final histology reported a 28*19*5 cm mass of
      endometrial tissue with no evidence of malignant transformation. The patient
      recovered well post-operatively and has remained asymptomatic. Our case
      illustrates that, despite being a common disease, endometriosis can masquerade as
      several other conditions and be missed or diagnosed late. Delay in diagnosis will
      not only prolong symptoms but can also compromise reproductive lifespan. It is
      therefore paramount that endometriosis is to be considered early in the
      management of premenopausal women who present with an irregular pelvic mass or
      hemorrhagic ascites.

PMID- 29043712
TI  - Uterus Dysplasia Associated with Cervico-Vaginal Agenesis.
AB  - Mullerian ducts can form upper parts of normal female reproductive system and any
      failure in ductal fusion may result in to mullerian duct anomalies (MDA). We
      present a case of MDA and a uterus dysplasia with no evidence of cervical or
      upper vaginal tissue. This case showes the role of magnetic resonace imaging
      (MRI) on MDA diagnosis and urges the need for a unified reliable and practical
      classification more compatible with clinical practice.

PMID- 29043713
TI  - Bioorthogonal chemical imaging of metabolic changes during epithelial-mesenchymal
      transition of cancer cells by stimulated Raman scattering microscopy.
AB  - Study of metabolic changes during epithelial-mesenchymal transition (EMT) of
      cancer cells is important for basic understanding and therapeutic management of
      cancer progression. We here used metabolic labeling and stimulated Raman
      scattering (SRS) microscopy, a strategy of bioorthogonal chemical imaging, to
      directly visualize changes in anabolic metabolism during cancer EMT at a single
      cell level. MCF-7 breast cancer cell is employed as a model system. Four types of
      metabolites (amino acids, glucose, fatty acids, and choline) are labeled with
      either deuterium or alkyne (C=C) tag. Their intracellular incorporations into MCF
      7 cells before or after EMT are visualized by SRS imaging targeted at the
      signature vibration frequency of C-D or C=C bonds. Overall, after EMT, anabolism
      of amino acids, glucose, and choline is less active, reflecting slower protein
      and membrane synthesis in mesenchymal cells. Interestingly, we also observed less
      incorporation of glucose and palmitate acids into membrane lipids, but more of
      them into lipid droplets in mesenchymal cells. This result indicates that,
      although mesenchymal cells synthesize fewer membrane lipids, they are actively
      storing energy into lipid droplets, either through de novo lipogenesis from
      glucose or direct scavenging of exogenous free fatty acids. Hence, metabolic
      labeling coupled with SRS can be a straightforward method in imaging cancer
      metabolism.

PMID- 29043714
TI  - Spectroscopic Doppler analysis for visible-light optical coherence tomography.
AB  - Retinal oxygen metabolic rate can be effectively measured by visible-light
      optical coherence tomography (vis-OCT), which simultaneously quantifies oxygen
      saturation and blood flow rate in retinal vessels through spectroscopic analysis
      and Doppler measurement, respectively. Doppler OCT relates phase variation
      between sequential A-lines to the axial flow velocity of the scattering medium.
      The detectable phase shift is between -pi and pi due to its periodicity, which
      limits the maximum measurable unambiguous velocity without phase unwrapping.
      Using shorter wavelengths, vis-OCT is more vulnerable to phase ambiguity since
      flow induced phase variation is linearly related to the center wavenumber of the
      probing light. We eliminated the need for phase unwrapping using spectroscopic
      Doppler analysis. We split the whole vis-OCT spectrum into a series of narrow
      subbands and reconstructed vis-OCT images to extract corresponding Doppler phase
      shifts in all the subbands. Then, we quantified flow velocity by analyzing
      subband-dependent phase shift using linear regression. In the phantom experiment,
      we showed that spectroscopic Doppler analysis extended the measurable absolute
      phase shift range without conducting phase unwrapping. We also tested this method
      to quantify retinal blood flow in rodents in vivo.

PMID- 29043715
TI  - Quantitative light-induced fluorescence technology for quantitative evaluation of
      tooth wear.
AB  - Various technologies used to objectively determine enamel thickness or dentin
      exposure have been suggested. However, most methods have clinical limitations.
      This study was conducted to confirm the potential of quantitative light-induced
      fluorescence (QLF) using autofluorescence intensity of occlusal surfaces of worn
      teeth according to enamel grinding depth in vitro. Sixteen permanent premolars
      were used. Each tooth was gradationally ground down at the occlusal surface in
      the apical direction. QLF-digital and swept-source optical coherence tomography
      images were acquired at each grinding depth (in steps of 100  MUm). All QLF
      images were converted to 8-bit grayscale images to calculate the fluorescence
      intensity. The maximum brightness (MB) values of the same sound regions in
      grayscale images before (MBbaseline) and phased values after (MBworn) the
      grinding process were calculated. Finally, 13 samples were evaluated. MBworn
      increased over the grinding depth range with a strong correlation (r=0.994,
      P<0.001). In conclusion, the fluorescence intensity of the teeth and grinding
      depth was strongly correlated in the QLF images. Therefore, QLF technology may be
      a useful noninvasive tool used to monitor the progression of tooth wear and to
      conveniently estimate enamel thickness.

PMID- 29043716
TI  - Trust, but in what?

PMID- 29043717
TI  - ?

PMID- 29043718
TI  - [A woman in her 60s with diarrhea and joint pain].

PMID- 29043719
TI  - Varicella zoster virus - need for better infection prevention and control.

PMID- 29043720
TI  - ?

PMID- 29043722
TI  - ?

PMID- 29043721
TI  - [In-hospital stroke].

PMID- 29043723
TI  - ?

PMID- 29043724
TI  - ?

PMID- 29043726
TI  - ?

PMID- 29043725
TI  - ?

PMID- 29043727
TI  - ?

PMID- 29043728
TI  - ?

PMID- 29043729
TI  - ?

PMID- 29043730
TI  - [Not sham in Norwegian].

PMID- 29043731
TI  - ?

PMID- 29043732
TI  - ?

PMID- 29043733
TI  - [Properties of cancer cell DNA affects the prognosis].
AB  - BACKGROUND: When diagnosing cancer, it is often difficult to predict the further
      growth and spread of the tumour. One of the features of cancer is an abnormality
      in the amount of DNA in cancer cell nuclei, so-called DNA aneuploidy. Extensive
      abnormalities are often due to an unstable genome, which leads to an accumulation
      of mutations, dysregulation of genes and loss of cell cycle control. This article
      aims to provide an overview of the prognostic value of DNA ploidy analyses in
      ovarian, endometrial, prostate and colorectal carcinoma. MATERIAL AND METHOD:
      This review article is based on literature searches in PubMed for the period 2000
      2016. RESULTS: The search resulted in 308 articles. Thirty-three of these,
      representing an analysis of more than 18 000 tumours, fulfilled the inclusion
      criteria. In 30 of the 33 articles, a significant correlation was found between
      DNA ploidy and disease outcome for patients with ovarian, endometrial, prostate
      and colorectal carcinoma. Patients with aneuploid tumours had a poorer prognosis
      than those with diploid tumours. INTERPRETATION: DNA ploidy analysis is a
      prognostic method for patients with ovarian and endometrial carcinoma, and is
      used as a guide to options for supplemental treatment and fertility-sparing
      surgery. A review of publications in recent years of DNA ploidy analyses for
      prostate and colorectal carcinoma reveals that these patient groups may also
      benefit from these measurements. In general terms, DNA ploidy analyses may help
      to increase knowledge of who needs supplemental treatment and who does not -
      which may be advantageous in avoiding overtreatment.

PMID- 29043734
TI  - ?

PMID- 29043735
TI  - [Logistic regression - applied and applicable].

PMID- 29043736
TI  - Renal involvement in paediatric systemic vasculitis.
AB  - BACKGROUND: Primary systemic vasculitis is a rare condition in children, which
      often has a slowly progressive course with diffuse symptoms and is therefore
      easily overlooked. Early initiation of treatment can prevent severe kidney
      disease. The aim of this study was to survey the extent of renal involvement in
      children with systemic vasculitis at Oslo University Hospital, Rikshospitalet.
      MATERIAL AND METHOD: This observational retrospective study was based on a review
      of medical records, laboratory results and renal biopsies from first admission to
      last check-up at Oslo University Hospital, Rikshospitalet, for the period 2000
      14. RESULTS: A total of 66 children (35 boys) under 18 years of age were treated
      at the hospital for primary systemic vasculitis in the period in question.
      Objective signs of renal involvement were found in 39 (59 %) at the first
      consultation and in 42 (64 %) over the course of the disease. Twenty-nine
      patients (44 %) underwent renal biopsy. Of the 41 patients with proven renal
      involvement that were still alive at the time of the last check-up, 12 continued
      to require treatment for renal impairment. Three patients had undergone renal
      transplantation, 18 were in remission on immunosuppressive or antihypertensive
      treatment, while 11 patients had achieved medication-free renal remission.
      INTERPRETATION: There is a high prevalence of renal involvement in paediatric
      patients treated for systemic vasculitis at Oslo University Hospital,
      Rikshospitalet. At their final check-up, the majority of patients continue to
      require treatment and follow-up for kidney disease.

PMID- 29043737
TI  - ?

PMID- 29043738
TI  - ?

PMID- 29043739
TI  - ?

PMID- 29043740
TI  - [Regulations on management and quality improvement in healthcare].

PMID- 29043741
TI  - ?

PMID- 29043742
TI  - ?

PMID- 29043743
TI  - ?

PMID- 29043744
TI  - ?

PMID- 29043745
TI  - Treatment of wrist fractures 2009-14.
AB  - BACKGROUND: The purpose of the study was to conduct a systematic analysis based
      on data from the Norwegian Patient Registry and describe the incidence and
      treatment of wrist fractures among adults, at national level and in the catchment
      areas of the various regional health authorities. MATERIAL AND METHOD: A search
      was conducted in the Norwegian Patient Registry for all patients aged >= 18 years
      with diagnosis codes for wrist fractures in the period 2009-2014. Age, sex and
      type of treatment were recorded. The results are presented as rates adjusted for
      age and sex for the catchment areas of Norway's 21 regional health authorities.
      RESULTS: In the period 2009-2014, a total of 75 132 patients aged >= 18 years
      were registered as having a wrist fracture. Almost 1/3 of these patients received
      operative treatment. During this period, the age- and sex-adjusted rate of wrist
      fractures in Norway averaged 244 per 100 000 inhabitants per year. Operation
      rates varied across catchment areas by a factor of three, and the use of plates
      by a factor of nine. INTERPRETATION: We found great variation in clinical
      practice, which is reflected in differences in operation rates and choice of
      surgical method across the catchment areas to which the patients belong.

PMID- 29043746
TI  - ?

PMID- 29043747
TI  - ?

PMID- 29043748
TI  - ?

PMID- 29043749
TI  - Oculomotor nerve palsy.

PMID- 29043750
TI  - ?

PMID- 29043751
TI  - ?

PMID- 29043752
TI  - ?

PMID- 29043753
TI  - Chlamydia testing in practice - requisitioners and patients.
AB  - BACKGROUND: Optimising the diagnostic work-up and treatment of genital chlamydia
      infection requires knowledge of the sampling patterns of those who order
      chlamydia tests. We wished to determine which groups of doctors collect specimens
      for chlamydia testing, and to examine the sex and age distribution of patients
      tested, and the proportion of positive tests, from general practitioners,
      gynaecologists in private practice, and youth health services. MATERIAL AND
      METHOD: The study includes 43 465 specimens analysed for genital infection with
      Chlamydia trachomatis at Vestfold Hospital Trust over the period 1 January 2007
      to 31 December 2011. Data from the laboratory information system were used to
      classify the test requisitioners. RESULTS: General practitioners requisitioned 60
      % of all chlamydia tests and 63 % of all positive tests. Youth health services
      requisitioned 13 % of all tests and 22 % of positive tests; gynaecologists in
      private practice, 12 % of all tests and 5 % of positive tests. Overall, 26 % of
      specimens were from women over the age of 30 with 2.2 % testing positive, and 82
      % of these specimens were submitted by general practitioners or gynaecologists in
      private practice. Twenty-three per cent of specimens were from men, and 78 % of
      these were collected in general practice. INTERPRETATION: Knowledge of who
      requisitions chlamydia testing and of whom is important for planning and
      improving chlamydia diagnosis, treatment and contact tracing. In this study from
      Norway, we found that doctors in general practice play a key role in diagnosing
      and treating chlamydia. The testing of women over the age of 30 by general
      practitioners and gynaecologists in private practice probably leads to
      unnecessary use of resources and should be reduced.

PMID- 29043754
TI  - ?

PMID- 29043755
TI  - ?

PMID- 29043756
TI  - ?

PMID- 29043757
TI  - There is no association between the presence of anti-thyroid antibodies and
      increased reproductive loss in pregnant women after ART: a systematic review and
      meta-analysis.
AB  - Women submitted to ART treatments represent a select subgroup of individuals.
      Several studies have described the relationship between TAI and pregnancy
      outcomes as a result of ART, with contradictory results. The purpose of this
      systematic review was to determine the association between TAI and the risk of
      miscarriage in pregnancies resulting from ART. MEDLINE via PubMed, LILACS and
      Embase were searched for studies published in peer-reviewed journals from 1999 to
      2017. The studies were summarized using the fixed effects model and the Peto's
      method to calculate RR in order to flesh out the association between TAI and
      spontaneous abortion. Only four papers were included in this systematic review
      and meta-analysis. Thirty-one miscarriages were observed in 210 clinical
      pregnancies of women with antithyroid antibodies; and 158 miscarriages were seen
      in 1,371 pregnancies without antithyroid antibodies. The meta-analysis failed to
      find an association between TAI and higher risk of reproductive loss, RR=0.94 95%
      confidence interval: 0.71-1.24; p=0.879. In conclusion, the presence of
      antithyroid antibodies was not associated with increased reproductive loss in
      patients submitted to ART treatments. It is our opinion that the presence of
      antithyroid antibodies should be considered as a secondary biomarker of
      autoimmune disease, rather than an actual cause of miscarriage in patients
      undergoing ART. Due to the small amount of evidence on the matter, the
      determination of TAI before the initiation of ART should be limited to research
      contexts.

PMID- 29043758
TI  - Commentary - Food environment and vulnerable populations: challenges and
      opportunities for policy.

PMID- 29043759
TI  - "Highly processed, highly packaged, very unhealthy. But they are low risk":
      exploring intersections between community food security and food safety.
AB  - INTRODUCTION: Food insecurity and foodborne disease are important issues in
      Canada, and the public health actions taken to address them can be conceptualized
      as factors shaping the food environment. Given emerging evidence that these two
      areas may interrelate, the objective of this study was to explore ways in which
      community food security efforts and food safety practices (and the population
      health issues they aim to address) may intersect in British Columbia, Canada, and
      interpret what this might mean for conceptualizing and attaining healthier food
      environments. METHODS: We conducted 14 key informant interviews with
      practitioners working in community food security and food safety in British
      Columbia, and used qualitative descriptive analysis to identify examples of
      intersections between the sectors. RESULTS: Participants identified four key ways
      that the two sectors intersect. They identified (1) how their daily practices to
      promote safe or healthy food could be helped or hindered by the activities of the
      other sector; (2) that historically disjointed policies that do not consider
      multiple health outcomes related to food may complicate the interrelationship;
      (3) that the relationship of these sectors is also affected by the fact that
      specific types of food products, such as fresh produce, can be considered both
      risky and beneficial; and (4) that both sectors are working towards the same goal
      of improved population health, albeit viewing it through slightly different
      lenses. CONCLUSION: Food security and food safety connect in several ways, with
      implications for characterizing and improving Canadian food environments.
      Collaboration across separated public health areas related to food is needed when
      designing new programs or policies aimed at changing the way Canadians eat.

PMID- 29043760
TI  - Retail food environments, shopping experiences, First Nations and the provincial
      Norths.
AB  - INTRODUCTION: This paper looks at the market food environments of First Nations
      communities located in the provincial Norths by examining the potential retail
      competition faced by the North West Company (NWC) and by reporting on the grocery
      shopping experiences of people living in northern Canada. METHODS: We employed
      two methodological approaches to assess northern retail food environments. First,
      we mapped food retailers in the North to examine the breadth of retail
      competition in the provincial Norths, focussing specifically on those communities
      without year-round road access. Second, we surveyed people living in communities
      in northern Canada about their retail and shopping experiences. RESULTS: Fifty
      four percent of communities in the provincial Norths and Far North without year
      round road access did not have a grocery store that competed with the NWC. The
      provinces with the highest percentage of northern communities without retail
      competition were Ontario (87%), Saskatchewan (83%) and Manitoba (72%).
      Respondents to the survey (n = 92) expressed concern about their shopping
      experiences in three main areas: the cost of food, food quality and freshness,
      and availability of specific foods. CONCLUSION: There is limited retail
      competition in the provincial Norths. In Manitoba, Saskatchewan and Ontario, the
      NWC has no store competition in at least 70% of northern communities. Consumers
      living in northern Canada find it difficult to afford nutritious foods and would
      like access to a wider selection of perishable foods in good condition.

PMID- 29043761
TI  - Exploring sales data during a healthy corner store intervention in Toronto: the
      Food Retail Environments Shaping Health (FRESH) project.
AB  - INTRODUCTION: Population health interventions in the retail food environment,
      such as corner store interventions, aim to influence the kind of cues consumers
      receive so that they are more often directed toward healthier options. Research
      that addresses financial aspects of retail interventions, particularly using
      outcome measures such as store sales that are central to retail decision making,
      is limited. This study explored store sales over time and across product
      categories during a healthy corner store intervention in a lowincome
      neighbourhood in Toronto, Ontario. METHODS: Sales data (from August 2014 to April
      2015) were aggregated by product category and by day. We used Microsoft Excel
      pivot tables to summarize and visually present sales data. We conducted t-tests
      to examine differences in product category sales by "peak" versus "nonpeak" sales
      days. RESULTS: Overall store sales peaked on the days at the end of each month,
      aligned with the issuing of social assistance payments. Revenue spikes on peak
      sales days were driven predominantly by transit pass sales. On peak sales days,
      mean sales of nonnutritious snacks and cigarettes were marginally higher than on
      other days of the month. Finally, creative strategies to increase sales of fresh
      vegetables and fruits seemed to substantially increase revenue from these product
      categories. CONCLUSION: Store sales data is an important store-level metric of
      food environment intervention success. Furthermore, data-driven decision making
      by retailers can be important for tailoring interventions. Future interventions
      and research should consider partnerships and additional success metrics for
      retail food environment interventions in diverse Canadian contexts.

PMID- 29043762
TI  - Food deserts in Winnipeg, Canada: a novel method for measuring a complex and
      contested construct.
AB  - INTRODUCTION: "Food deserts" have emerged over the past 20 years as spaces of
      concern for communities, public health authorities and researchers because of
      their potential negative impact on dietary quality and subsequent health
      outcomes. Food deserts are residential geographic spaces, typically in urban
      settings, where low-income residents have limited or no access to retail food
      establishments with sufficient variety at affordable cost. Research on food
      deserts presents methodological challenges including retail food store
      identification and classification, identification of low-income populations, and
      transportation and proximity metrics. Furthermore, the complex methods often used
      in food desert research can be difficult to reproduce and communicate to key
      stakeholders. To address these challenges, this study sought to demonstrate the
      feasibility of implementing a simple and reproducible method of identifying food
      deserts using data easily available in the Canadian context. METHODS: This study
      was conducted in Winnipeg, Canada in 2014. Food retail establishments were
      identified from Yellow Pages and verified by public health dietitians. We
      calculated two scenarios of food deserts based on location of the lowest-income
      quintile population: (a) living >= 500 m from a national chain grocery store, or
      (b) living >= 500 m from a national chain grocery store or a full-service grocery
      store. RESULTS: The number of low-income residents living in a food desert ranged
      from 64 574 to 104 335, depending on the scenario used. CONCLUSION: This study
      shows that food deserts affect a significant proportion of the Winnipeg
      population, and while concentrated in the urban core, exist in suburban
      neighbourhoods also. The methods utilized represent an accessible and
      transparent, reproducible process for identifying food deserts. These methods can
      be used for costeffective, periodic surveillance and meaningful engagement with
      communities, retailers and policy makers.

PMID- 29043763
TI  - Status report - Geographic retail food environment measures for use in public
      health.
AB  - The Association of Public Health Epidemiologists in Ontario (APHEO) Core
      Indicators Work Group standardizes definitions and calculation methods for over
      120 public health indicators to enhance accurate and standardized community
      health status reporting across public health units in Ontario. The Built
      Environment Subgroup is a multi-disciplinary group made up of planners,
      researchers, policy analysts, registered dietitians, geographic information
      systems (GIS) analysts and epidemiologists. The Subgroup selected and
      operationalized a suite of objective, standardized indicators intended to help
      public health units and regional health authorities assess their community retail
      food environments. The Subgroup proposed three indicators that use readily
      available data sources and GIS tools to characterize geographic access to various
      types of retail food outlets within neighbourhoods in urban settings. This
      article provides a status report on the development of these food environment
      indicators.

PMID- 29043764
TI  - At-a-glance - Sentinel surveillance of emergency department presentations for
      barbecue brush-related injuries: the electronic Canadian Hospitals Injury
      Reporting and Prevention Program, 2011 to 2017.
AB  - A barbecue (BBQ) brush is a common household item designed for cleaning grills
      used for barbecuing. Data from the electronic Canadian Hospitals Injury Reporting
      and Prevention Program database were analysed to estimate the frequency of
      injuries related to BBQ brushes as a proportion of all injuries, as well as to
      describe characteristics associated with such injury events. Between April 1,
      2011 and July 17, 2017, BBQ brush injuries were observed at a frequency of 1.5
      cases per 100 000 eCHIRPP cases (N = 12). Findings suggest that in addition to
      risks associated with the ingestion of loose BBQ brush bristles attached to
      foods, loose bristles could also result in injury via other mechanisms.

PMID- 29043765
TI  - Boosting the Visible-Light Photoactivity of BiOCl/BiVO4/N-GQD Ternary
      Heterojunctions Based on Internal Z-Scheme Charge Transfer of N-GQDs:
      Simultaneous Band Gap Narrowing and Carrier Lifetime Prolonging.
AB  - The efficient separation of photogenerated electron-hole pairs in photoactive
      materials is highly desired, allowing their transfer to specific sites for
      undergoing redox reaction in various applications. The construction of ternary
      heterojunctions is a practical strategy to enhance the migration of
      photogenerated electron that realizes the synergistic effect of multicomponents
      rather than the simple overlay of single component. Here, we demonstrate an
      available way to fabricate new BiOCl/BiVO4/nitrogen-doped graphene quantum dot (N
      GQD) ternary heterojunctions that exhibit higher efficiency in charge separation
      than any binary heterojunction or pure material under visible-light irradiation.
      UV-vis diffuse reflectance spectroscopy demonstrated that the proposed
      BiOCl/BiVO4/N-GQD ternary heterojunctions possess the narrower band gap energy.
      More importantly, the ternary heterojunctions reveal the prolonged lifetime of
      photogenerated charges and enhanced the separation efficiency of photogenerated
      electron-hole pairs, which may be ascribed to sensitization based on an internal
      Z-scheme charge transfer at the interface of N-GQDs with oxygen functional
      groups. Furthermore, we examine the photoactive performance of proposed ternary
      heterojunctions in aqueous solution by using the photodegradation of bisphenol A
      as a model system and BiOCl/BiVO4/N-GQD ternary heterojunctions also display a
      dramatically enhanced photodegradation rate. The proposed charge separation and
      transfer process of BiOCl/BiVO4/N-GQD ternary heterojunctions for the enhanced
      photoactivity were deduced by electrochemical measurements, photoluminescence,
      and electron spin resonance. The results demonstrate that a Z-scheme charge
      process was formed between BiOCl/BiVO4 binary heterojunctions and N-GQDs, leading
      to an efficient charge carrier separation and strong photocatalytic ability.
      Notably, this work may assist in a better understanding of the role of N-GQDs in
      kinds of heterojunctions. Conceivably, it can be extended to fabricate other
      photocatalytic systems and photoelectrochemical platforms associated with
      photoactive materials.

PMID- 29043766
TI  - Solution-Processed Metal-Oxide p-n Charge Generation Junction for High
      Performance Inverted Quantum-Dot Light-Emitting Diodes.
AB  - We report solution-processed metal-oxide p-n junction, Li-doped CuO (Li:CuO) and
      Li-doped ZnO (Li:ZnO), as a charge generation junction (CGJ) in quantum-dot light
      emitting diode (QLED) at reverse bias. Efficient charge generation is
      demonstrated in a stack of air-annealed Li:CuO and Li:ZnO layers in QLEDs. Air
      annealing of Li:ZnO on Li:CuO turns out to be a key process to decrease oxygen
      vacancy (Vo) and increase the copper (II) oxide (CuO) fraction at the
      Li:CuO/Li:ZnO interface for efficient charge generation. Green QLEDs
      incorporating Li:CuO/Li:ZnO CGJ show the maximum current and power efficiencies
      of 35.4 cd/A and 33.5 lm/W, respectively.

PMID- 29043767
TI  - Synthesis of Ag3PO4 Crystals with Tunable Shapes for Facet-Dependent Optical
      Property, Photocatalytic Activity, and Electrical Conductivity Examinations.
AB  - This work has developed conditions for the synthesis of Ag3PO4 cubes, rhombic
      dodecahedra, {100}-truncated rhombic dodecahedra, tetrahedra, and tetrapods by
      tuning the amount of NH4NO3, NaOH, AgNO3, and K2HPO4 solutions added. Use of a
      minimal amount of AgNO3 solution can form much smaller rhombic dodecahedra and
      tetrahedra. Submicrometer-sized Ag3PO4 cubes and rhombic dodecahedra with sizes
      larger than 300 nm do not exhibit the optical size effect, but ~290 nm rhombic
      dodecahedra show a smaller band gap value than larger cubes, and tetrahedra show
      the most blue-shifted absorption edge. The optical facet effect is present in
      Ag3PO4 crystals. Ag3PO4 cubes are more photocatalytically active than rhombic
      dodecahedra toward photodegradation of methyl orange, but tetrahedra are
      inactive, showing clear presence of photocatalytic facet effects. Electron
      paramagnetic resonance results confirm much higher production of hydroxyl
      radicals from photoirradiated Ag3PO4 cubes than from rhombic dodecahedra, while
      tetrahedra yield essentially no radicals. A modified band diagram showing
      different degrees of band edge bending can explain these observations. All these
      Ag3PO4 crystals show poor electrical conductivity properties, but the {110} faces
      are slightly more conductive than the {100} faces. As a result, current
      rectifying I-V curves have been obtained, demonstrating that facet-dependent
      electrical properties are broadly observable in many semiconductor materials.
      This work reveals again that facet-dependent optical, photocatalytic, and
      electrical conductivity properties are intrinsic semiconductor properties.

PMID- 29043768
TI  - Infection of iPSC Lines with Miscarriage-Associated Coxsackievirus and Measles
      Virus and Teratogenic Rubella Virus as a Model for Viral Impairment of Early
      Human Embryogenesis.
AB  - Human induced pluripotent stem cell (iPSC) lines are a promising model for the
      early phase of human embryonic development. Here, their contribution to the still
      incompletely understood pathogenesis of congenital virus infections was
      evaluated. The infection of iPSC lines with miscarriage-associated coxsackievirus
      B3 (CVB3) and measles virus (MV) was compared to the efficient teratogen rubella
      virus (RV). While CVB3 and MV were found to be cytopathogenic on iPSC lines, RV
      replicated without impairment of iPSC colony morphology and integrity. This so
      far outstanding course of infection enabled maintenance of RV-infected iPSC
      cultures over several passages and their subsequent differentiation to ectoderm,
      endoderm, and mesoderm. A modification of the metabolic profile of infected iPSC
      lines was the only common aspect for all three viruses. This study points toward
      two important aspects. First, iPSC lines represent a suitable cell culture model
      for early embryonic virus infection. Second, metabolic activity represents an
      important means for evaluation of pathogen-associated alterations in iPSC lines.

PMID- 29043769
TI  - Nitrogen-Rich Conjugated Microporous Polymers: Facile Synthesis, Efficient Gas
      Storage, and Heterogeneous Catalysis.
AB  - Nitrogen-rich conjugated microporous polymers (NCMPs) have attracted great
      attention in recent years owing to their polarity, basicity, and ability to
      coordinate metal ions. Herein, three NCMPs, structurally close to polyaniline,
      were facilely synthesized via chemical oxidative polymerization between
      multiconnected aniline precursors. The NCMPs with high N content (11.84 wt %),
      intrinsic ultramicroporosity (<1 nm), and moderate surface area (485 m2 g-1) show
      wide-ranging adsorption functionality, e.g., CO2 uptake (11 wt %) and CO2
      selectivity over N2 (360, 1 bar), 1.0 wt % H2 storage, as well as 215 wt % iodine
      vapor uptake at ambient pressure. Moreover, these NCMPs act as support for
      palladium catalysts and can maintain >94% activity in Suzuki-Miyaura coupling
      reactions after six continuous runs.

PMID- 29043771
TI  - Narrowing Plasmon Resonance Linewidth of Au Nanodome Lattices.
AB  - Gold hollow nanodomes arranged in hexagonal lattices support surface plasmon
      polaritons (SPPs) propagating at air-Au interface. The cross-sectional heights of
      the continuous and hierarchical hexagonal nanodome arrays can be altered by a
      simple thermal treatment, and the change in nanodome size leads to a significant
      linewidth narrowing of plasmon resonance because of reduced scattering loss.
      Taking the variation in the SPP intensities into account, the surface modulation
      depth is found to be around 100 nm for achieving a longer propagation length of
      SPP.

PMID- 29043772
TI  - Therapeutic Angiogenesis via Solar Cell-Facilitated Electrical Stimulation.
AB  - Cell therapy has been suggested as a treatment modality for ischemic diseases,
      but the poor survival and engraftment of implanted cells limit its therapeutic
      efficacy. To overcome such limitation, we used electrical stimulation (ES)
      derived from a wearable solar cell for inducing angiogenesis in ischemic tissue.
      ES enhanced the secretion of angiogenic growth factors and the migration of
      mesenchymal stem cells (MSCs), myoblasts, endothelial progenitor cells, and
      endothelial cells in vitro. In a mouse ischemic hindlimb model, ES generated by a
      solar cell and applied to the ischemic region promoted migration of MSCs toward
      the ischemic site and upregulated expression of angiogenic paracrine factors
      (vascular endothelial, basic fibroblast, and hepatocyte growth factors; and
      stromal cell-derived factor-1alpha). Importantly, solar cell-generated ES
      promoted the formation of capillaries and arterioles at the ischemic region,
      attenuated muscle necrosis and fibrosis, and eventually prevented loss of the
      ischemic limb. Solar cell ES therapy showed higher angiogenic efficacy than
      conventional MSC therapy. This study shows the feasibility of using solar cell ES
      as a novel treatment for therapeutic angiogenesis.

PMID- 29043770
TI  - A Novel Negative Allosteric Modulator Selective for GluN2C/2D-Containing NMDA
      Receptors Inhibits Synaptic Transmission in Hippocampal Interneurons.
AB  - N-Methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors that
      mediate excitatory synaptic transmission and have been implicated in numerous
      neurological disorders. NMDARs typically comprise two GluN1 and two GluN2
      subunits. The four GluN2 subtypes (GluN2A-GluN2D) have distinct functional
      properties and gene expression patterns, which contribute to diverse functional
      roles for NMDARs in the brain. Here, we present a series of GluN2C/2D-selective
      negative allosteric modulators built around a N-aryl benzamide (NAB) core. The
      prototypical compound, NAB-14, is >800-fold selective for recombinant
      GluN2C/GluN2D over GluN2A/GluN2B in Xenopus oocytes and has an IC50 value of 580
      nM at recombinant GluN2D-containing receptors expressed in mammalian cells. NAB
      14 inhibits triheteromeric (GluN1/GluN2A/GluN2C) NMDARs with modestly reduced
      potency and efficacy compared to diheteromeric (GluN1/GluN2C/GluN2C) receptors.
      Site-directed mutagenesis suggests that structural determinants for NAB-14
      inhibition reside in the GluN2D M1 transmembrane helix. NAB-14 inhibits GluN2D
      mediated synaptic currents in rat subthalamic neurons and mouse hippocampal
      interneurons, but has no effect on synaptic transmission in hippocampal pyramidal
      neurons, which do not express GluN2C or GluN2D. This series possesses some
      druglike physical properties and modest brain permeability in rat and mouse.
      Altogether, this work identifies a new series of negative allosteric modulators
      that are valuable tools for studying GluN2C- and GluN2D-containing NMDAR function
      in brain circuits, and suggests that the series has the potential to be developed
      into therapies for selectively modulating brain circuits involving the GluN2C and
      GluN2D subunits.

PMID- 29043773
TI  - Coherence Spectroscopy in the Condensed Phase: Insights into Molecular Structure,
      Environment, and Interactions.
AB  - The role of coherences, or coherently excited superposition states, in complex
      condensed-phase systems has been the topic of intense interest and debate for a
      number of years. In many cases, coherences have been utilized as spectators of
      ultrafast dynamics or for identifying couplings between electronic states. In
      rare cases, they have been found to drive excited state dynamics directly.
      Interestingly though, the utilization of coherences as a tool for high-detail
      vibronic spectroscopy has largely been overlooked until recently, despite their
      encoding of key information regarding molecular structure, electronically
      sensitive vibrational modes, and intermolecular interactions. Furthermore, their
      detection in the time domain makes for a highly comprehensive spectroscopic
      technique wherein the phase and dephasing times are extracted in addition to
      amplitude and intensity, an element not afforded in analogous frequency domain
      "steady-state" measurements. However, practical limitations arise in
      disentangling the large number of coherent signals typically accessed in
      broadband nonlinear spectroscopic experiments, often complicating assignment of
      the origin and type of coherences generated. Two-dimensional electronic
      spectroscopy (2DES) affords an avenue by which to disperse and decompose the
      large number of coherent signals generated in nonlinear experiments, facilitating
      the assignment of various types of quantum coherences. 2DES takes advantage of
      the broad bandwidth necessary for achieving the high time resolution desired for
      ultrafast dynamics and coherence generation by resolving the excitation axis to
      detect all excitation channels independently. This feature is beneficial for
      following population dynamics such as electronic energy transfer, and 2DES has
      become the choice method for such studies. Simultaneously, coherences arise as
      oscillations at well-defined coordinates across the 2D map often atop those
      evolving population signals. By isolating the coherent contribution to the 2DES
      data and Fourier transforming along the population time, a 3D spectral
      representation of the coherent 2D data is generated, and coherences are then
      ordered by their oscillation frequency, nu2. Individual coherences can then be
      selected by their frequency and evaluated via their distinct "2D coherence"
      spectra, yielding a significantly more distinctive set of spectroscopic
      signatures over other 1D methodologies and single-point 2DES analysis. Given that
      coherences of different origin result in unique 2D coherence spectra, these
      characteristics can be catalogued and compared directly against experiment for
      prompt assignment, a strategy not afforded by traditional 2DES analysis. In this
      Account, a structure-driven time-independent spectral model is discussed and
      employed to compare the 2D fingerprints of various coherences to experimental 2D
      coherence spectra. The frequency-domain approach can easily integrate ab initio
      derived vibronic parameters, and its correspondence with experimental coherence
      spectra of a model compound is demonstrated. Several examples and applications
      are discussed herein, from 2D Franck-Condon analysis of a model compound, to
      identifying the signatures of interpigment vibronic coupling in a photosynthetic
      light-harvesting complex. The 3D spectral approach to 2DES provides remarkable
      spectroscopic detail, in turn leading to new insights in molecular structure and
      interactions, which complement the time-resolved dynamics simultaneously
      recorded. The approach presented herein has the potential to distill down the
      convoluted set of nonlinear signals appearing in 2D coherent spectra, making the
      technique more amenable to high-detail vibronic spectroscopy in inherently
      complex condensed phase systems.

PMID- 29043775
TI  - Double-Sided Electrochromic Device Based on Metal-Organic Frameworks.
AB  - Devices displaying controllably tunable optical properties through an applied
      voltage are attractive for smart glass, mirrors, and displays. Electrochromic
      material development aims to decrease power consumption while increasing the
      variety of attainable colors, their brilliance, and their longevity. We report
      the first electrochromic device constructed from metal organic frameworks (MOFs).
      Two MOF films, HKUST-1 and ZnMOF-74, are assembled so that the oxidation of one
      corresponds to the reduction of the other, allowing the two sides of the device
      to simultaneously change color. These MOF films exhibit cycling stability
      unrivaled by other MOFs and a significant optical contrast in a lithium-based
      electrolyte. HKUST-1 reversibly changed from bright blue to light blue and ZnMOF
      74 from yellow to brown. The electrochromic device associates the two MOF films
      via a PMMA-lithium based electrolyte membrane. The color-switching of these MOFs
      does not arise from an organic-linker redox reaction, signaling unexplored
      possibilities for electrochromic MOF-based materials.

PMID- 29043774
TI  - Augmenting Influenza-Specific T Cell Memory Generation with a Natural Killer T
      Cell-Dependent Glycolipid-Peptide Vaccine.
AB  - The development of a universal vaccine for influenza A virus (IAV) that does not
      require seasonal modification is a long-standing health goal, particularly in the
      context of the increasing threat of new global pandemics. Vaccines that
      specifically induce T cell responses are of considerable interest because they
      can target viral proteins that are more likely to be shared between different
      virus strains and subtypes and hence provide effective cross-reactive IAV
      immunity. From a practical perspective, such vaccines should induce T cell
      responses with long-lasting memory, while also being simple to manufacture and
      cost-effective. Here we describe the synthesis and evaluation of a vaccine
      platform based on solid phase peptide synthesis and bio-orthogonal conjugation
      methodologies. The chemical approach involves covalently attaching synthetic long
      peptides from a virus-associated protein to a powerful adjuvant molecule, alpha
      galactosylceramide (alpha-GalCer). Strain-promoted azide-alkyne cycloaddition is
      used as a simple and efficient method for conjugation, and pseudoproline
      methodology is used to increase the efficiency of the peptide synthesis. alpha
      GalCer is a glycolipid that stimulates NKT cells, a population of lymphoid
      resident immune cells that can provide potent stimulatory signals to antigen
      presenting cells engaged in driving proliferation and differentiation of peptide
      specific T cells. When used in mice, the vaccine induced T cell responses that
      provided effective prophylactic protection against IAV infection, with the speed
      of viral clearance greater than that seen from previous viral exposure. These
      findings are significant because the vaccines are highly defined, quick to
      synthesize, and easily characterized and are therefore appropriate for large
      scale affordable manufacture.

PMID- 29043776
TI  - Art Advancing Science: Filmmaking Leads to Molecular Insights at the Nanoscale.
AB  - Many have recognized the potential value of facilitating activities that span the
      art-science interface for the benefit of society; however, there are few examples
      that demonstrate how pursuit of an artistic agenda can lead to scientific
      insights. Here, we describe how we set out to produce an entertaining short film
      depicting the fertilization of the egg by sperm as a parody of a preview for
      another Star Wars movie to excite the public about science, but ended up
      developing a simulation tool for multiscale modeling. To produce an aesthetic
      that communicates mechanical continuity across spatial scales, we developed
      custom strategies that integrate physics-based animation software from the
      entertainment industry with molecular dynamics simulation tools, using
      experimental data from research publications. Using this approach, we were able
      to depict biological physicality across multiple spatial scales, from how sperm
      tails move to collective molecular behavior within the axoneme to how the
      molecular motor, dynein, produces force at the nanometer scale. The dynein
      simulations, which were validated by replicating results of past simulations and
      cryo-electron microscopic studies, also predicted a potential mechanism for how
      ATP hydrolysis drives dynein motion along the microtubule as well as how dynein
      changes its conformation when it goes through the power stroke. Thus, pursuit of
      an artistic work led to insights into biology at the nanoscale as well as the
      development of a highly generalizable modeling and simulation technology that has
      utility for nanoscience and any other area of scientific investigation that
      involves analysis of complex multiscale systems.

PMID- 29043778
TI  - Tetraphenylethylene-Based AIE-Active Probes for Sensing Applications.
AB  - This Review provides a comprehensive analysis of recent development in the field
      of aggregation-induced emission (AIE)-active tetraphenylethylene (TPE)
      luminophores and their applications in biomolecular science. It begins with a
      discussion of the diverse range of structural motifs that have found particular
      applications in sensing, and demonstrates that TPE structures and their
      derivatives have been used for a diverse range of analytes such as such as H+,
      anions, cations, heavy metals, organic volatiles, and toxic gases. Advances are
      discussed in depth where TPE is utilized as a mechanoluminescent material in
      bioinspired receptor units with specificity for analytes for such as glucose or
      RNA. The rapid advances in sensor research make this summary of recent
      developments in AIE-active TPE luminophores timely, in order to disseminate the
      advantages of these materials for sensing of analytes in solution, as well as the
      importance of solid and aggregated states in controlling sensing behavior.

PMID- 29043777
TI  - Isoform-Selective ATAD2 Chemical Probe with Novel Chemical Structure and Unusual
      Mode of Action.
AB  - ATAD2 (ANCCA) is an epigenetic regulator and transcriptional cofactor, whose
      overexpression has been linked to the progress of various cancer types. Here, we
      report a DNA-encoded library screen leading to the discovery of BAY-850, a potent
      and isoform selective inhibitor that specifically induces ATAD2 bromodomain
      dimerization and prevents interactions with acetylated histones in vitro, as well
      as with chromatin in cells. These features qualify BAY-850 as a chemical probe to
      explore ATAD2 biology.

PMID- 29043779
TI  - Reinforcing Germanium Electrode with Polymer Matrix Decoration for Long Cycle
      Life Rechargeable Lithium Ion Batteries.
AB  - Germanium is a promising anode material for lithium ion batteries because of its
      high theoretical specific capacity and low operation voltage. However, a
      significant challenge in using Ge-based anodes is the large volume variation
      during cycling that causes pulverization and capacity fade. Despite intense
      studies in the past decade, unsatisfactory cycling stability of the Ge-based
      electrodes still impedes their widespread applications. In this study, we
      demonstrate a high-performance electrode through the synergistic combination of a
      high-capacity Ge film grown on a three-dimensional current collector and an in
      situ formed poly(vinylidene fluoride)-hexafluoropropene/SiO2 protective layer.
      Specifically, the polymer matrix is in continuous contact with the surface of the
      Ge shell, which provides improved mechanical and ionic transport properties. As a
      highlight, we present impressive cycling stability over 3000 cycles at 1 C rate
      with a capacity retention as high as 95.7%. Furthermore, the LiCoO2-Ge full
      battery operates at an average voltage of 3.3 V at 0.5 C and maintains good
      electrochemical performance, suggesting great potential for applications in
      energy storage and conversion devices.

PMID- 29043780
TI  - Cucurbituril and Azide Cofunctionalized Graphene Oxide for Ultrasensitive Electro
      Click Biosensing.
AB  - To achieve high selectivity and sensitivity simultaneously in an electrochemical
      biosensing platform, cucurbituril and azide cofunctionalized graphene oxide, a
      new functional nanomaterial that acts as a go-between to connect the recognition
      element with amplified signal architecture, is developed in this work. The
      cucurbituril and azide cofunctionalized graphene oxide features a high specific
      surface area with abundant levels of the two types of functional groups.
      Specifically, it emerges as a powerful tool to link recognition elements with
      simplicity, high yield, rapidity, and highly selective reactivity through azide
      alkynyl click chemistry. Moreover, it possesses many host molecules to interact
      with guest molecules (also signal molecules)-grafted branched ethylene imine
      polymer, through which the detection sensitivity can be greatly improved.
      Together with electro-click technology, a highly controllable, selective, and
      sensitive biosensing platform can be easily created. For VEGF165 protein
      detection, the electro-click assay has high selectivity and sensitivity; a
      dynamic detection range from 10 fg mL-1 to 1 ng mL-1 with a detection limit of 8
      fg mL-1 was achieved. The electro-click biosensing strategy based on cucurbituril
      and azide cofunctionalized graphene oxide would have great promise for other
      target analytes with a broad range of applications.

PMID- 29043781
TI  - Direct Writing Electrospinning of Scaffolds with Multidimensional Fiber
      Architecture for Hierarchical Tissue Engineering.
AB  - Nanofibrous structures have long been used as scaffolds for tissue engineering
      (TE) applications, due to their favorable characteristics, such as high porosity,
      flexibility, high cell attachment and enhanced proliferation, and overall
      resemblance to native extracellular matrix (ECM). Such scaffolds can be easily
      produced at a low cost via electrospinning (ESP), but generally cannot be
      fabricated with a regular and/or complex geometry, characterized by macropores
      and uniform thickness. We present here a novel technique for direct writing (DW)
      with solution ESP to produce complex three-dimensional (3D) multiscale and
      ultrathin (~1 MUm) fibrous scaffolds with desirable patterns and geometries. This
      technique was simply achieved via manipulating technological conditions, such as
      spinning solution, ambient conditions, and processing parameters. Three different
      regimes in fiber morphologies were observed, including bundle with dispersed
      fibers, bundle with a core of aligned fibers, and single fibers. The transition
      between these regimes depended on tip to collector distance (Wd) and applied
      voltage (V), which could be simplified as the ratio V/Wd. Using this technique, a
      scaffold mimicking the zonal organization of articular cartilage was further
      fabricated as a proof of concept, demonstrating the ability to better mimic
      native tissue organization. The DW scaffolds directed tissue organization and
      fibril matrix orientation in a zone-dependent way. Comparative expression of
      chondrogenic markers revealed a substantial upregulation of Sox9 and aggrecan
      (ACAN) on these structures compared to conventional electrospun meshes. Our novel
      method provides a simple way to produce customized 3D ultrathin fibrous
      scaffolds, with great potential for TE applications, in particular those for
      which anisotropy is of importance.

PMID- 29043782
TI  - Interfacial Engineering with Cross-Linkable Fullerene Derivatives for High
      Performance Perovskite Solar Cells.
AB  - Two fullerene derivatives with styryl and oxetane cross-linking groups served as
      interfacial materials to modify an electron-transporting layer (ETL) of TiO2,
      doped with Au nanoparticles, processed under low-temperature conditions to
      improve the performance of perovskite solar cells (PSC). The cross-linkable [6,6]
      phenyl-C61-butyric styryl dendron ester was produced via thermal treatment at 160
      degrees C for 20 min, whereas the cross-linkable [6,6]-phenyl-C61-butyric
      oxetane dendron ester (C-PCBOD) was obtained via UV-curing treatment for 45 s.
      Both cross-linked fullerenes can passivate surface-trap states of TiO2 and have
      also excellent surface coverage on the TiO2 layer shown in the corresponding
      atomic force microscopy images. To improve the crystallinity of perovskite, we
      propose a simple co-solvent method involving mixing dimethylformamide (DMF) and
      dimethyl sulfoxide (DMSO) in a specific ratio (DMF/DMSO = 90/10). The fullerene
      derivative layer between the ETL and perovskite layers significantly improved
      electron extraction and suppressed charge recombination by decreasing the density
      of traps at the ETL surface. A planar PSC device was fabricated with the
      configuration indium tin oxide/TiO2 (Au)/C-PCBOD/perovskite/spiro-OMeTAD/Au to
      attain a power conversion efficiency (PCE) of 15.9%. The device performance was
      optimized with C-PCBOD as an interfacial mediate to modify the surface of the
      mesoporous TiO2 ETL; the C-PCBOD-treated device attained a significantly enhanced
      performance, PCE 18.3%. Electrochemical impedance spectral and photoluminescence
      decay measurements were carried out to understand the characteristics of electron
      transfer and charge recombination of the perovskite/TiO2 samples with and without
      a fullerene interfacial layer.

PMID- 29043783
TI  - Marine Mammal Microbiota Yields Novel Antibiotic with Potent Activity Against
      Clostridium difficile.
AB  - The recent explosion of research on the microbiota has highlighted the important
      interplay between commensal microorganisms and the health of their cognate hosts.
      Metabolites isolated from commensal bacteria have been demonstrated to possess a
      range of antimicrobial activities, and it is widely believed that some of these
      metabolites modulate host behavior, affecting predisposition to disease and
      pathogen invasion. Our access to the local marine mammal stranding network and
      previous successes in mining the fish microbiota poised us to test the hypothesis
      that the marine mammal microbiota is a novel source of commensal bacteria
      produced bioactive metabolites. Examination of intestinal contents from five
      marine mammals led to the identification of a Micromonospora strain with potent
      and selective activity against a panel of Gram-positive pathogens and no
      discernible human cytotoxicity. Compound isolation afforded a new complex
      glycosylated polyketide, phocoenamicin, with potent activity against the
      intestinal pathogen Clostridium difficile, an organism challenging to treat in
      hospital settings. Use of our activity-profiling platform, BioMAP, clustered this
      metabolite with other known ionophore antibiotics. Fluorescence imaging and flow
      cytometry confirmed that phocoenamicin is capable of shifting membrane potential
      without damaging membrane integrity. Thus, exploration of gut microbiota in hosts
      from diverse environments can serve as a powerful strategy for the discovery of
      novel antibiotics against human pathogens.

PMID- 29043784
TI  - Estimating the High-Arsenic Domestic-Well Population in the Conterminous United
      States.
AB  - Arsenic concentrations from 20 450 domestic wells in the U.S. were used to
      develop a logistic regression model of the probability of having arsenic >10
      MUg/L ("high arsenic"), which is presented at the county, state, and national
      scales. Variables representing geologic sources, geochemical, hydrologic, and
      physical features were among the significant predictors of high arsenic. For U.S.
      Census blocks, the mean probability of arsenic >10 MUg/L was multiplied by the
      population using domestic wells to estimate the potential high-arsenic domestic
      well population. Approximately 44.1 M people in the U.S. use water from domestic
      wells. The population in the conterminous U.S. using water from domestic wells
      with predicted arsenic concentration >10 MUg/L is 2.1 M people (95% CI is 1.5 to
      2.9 M). Although areas of the U.S. were underrepresented with arsenic data,
      predictive variables available in national data sets were used to estimate high
      arsenic in unsampled areas. Additionally, by predicting to all of the
      conterminous U.S., we identify areas of high and low potential exposure in areas
      of limited arsenic data. These areas may be viewed as potential areas to
      investigate further or to compare to more detailed local information. Linking
      predictive modeling to private well use information nationally, despite the
      uncertainty, is beneficial for broad screening of the population at risk from
      elevated arsenic in drinking water from private wells.

PMID- 29043785
TI  - Elevated Exposures to Polycyclic Aromatic Hydrocarbons and Other Organic Mutagens
      in Ottawa Firefighters Participating in Emergency, On-Shift Fire Suppression.
AB  - Occupational exposures to combustion emissions were examined in Ottawa Fire
      Service (OFS) firefighters. Paired urine and dermal wipe samples (i.e., pre- and
      post-event) as well as personal air samples and fire event questionnaires were
      collected from 27 male OFS firefighters. A total of 18 OFS office workers were
      used as additional controls. Exposures to polycyclic aromatic hydrocarbons (PAHs)
      and other organic mutagens were assessed by quantification of urinary PAH
      metabolite levels, levels of PAHs in dermal wipes and personal air samples, and
      urinary mutagenicity using the Salmonella mutagenicity assay (Ames test). Urinary
      Clara Cell 16 (CC16) and 15-isoprostane F2t (8-iso-PGF2alpha) levels were used to
      assess lung injury and overall oxidative stress, respectively. The results showed
      significant 2.9- to 5.3-fold increases in average post-event levels of urinary
      PAH metabolites, depending on the PAH metabolite (p < 0.0001). Average post-event
      levels of urinary mutagenicity showed a significant, event-related 4.3-fold
      increase (p < 0.0001). Urinary CC16 and 8-iso-PGF2alpha did not increase. PAH
      concentrations in personal air and on skin accounted for 54% of the variation in
      fold changes of urinary PAH metabolites (p < 0.002). The results indicate that
      emergency, on-shift fire suppression is associated with significantly elevated
      exposures to combustion emissions.

PMID- 29043786
TI  - Measuring Nanoparticle Attachment Efficiency in Complex Systems.
AB  - As process-based environmental fate and transport models for engineered
      nanoparticles are developed, there is a need for relevant and reliable measures
      of nanoparticle behavior. The affinity of nanoparticles for various surfaces
      (alpha) is one such measure. Measurements of the affinity of nanoparticles
      obtained by flowing particles through a porous medium are constrained by the
      types of materials or exposure scenarios that can be configured into such column
      studies. Utilizing glass beads and kaolinite as model collector surfaces, we
      evaluate a previously developed mixing method for measuring nanoparticle
      attachment to environmental surfaces, and validate this method with an equivalent
      static column system over a range of organic matter concentrations and ionic
      strengths. We found that, while both impacted heteroaggregation rates in a
      predictable manner when varied individually, neither dominated when both
      parameters were varied. The theory behind observed nanoparticle heteroaggregation
      rates (alphabetaB) to background particles in mixed systems is also
      experimentally validated, demonstrating both collision frequency (beta) and
      background particle concentration (B) to be independent for use in fate modeling.
      We further examined the effects of collector particle composition (kaolinite vs
      glass beads) and nanoparticle surface chemistry (PVP, citrate, or humic acid) on
      alpha, and found a strong dependence on both.

PMID- 29043787
TI  - Rate of Lipid Peroxyl Radical Production during Cellular Homeostasis Unraveled
      via Fluorescence Imaging.
AB  - Reactive oxygen species (ROS) and their associated byproducts have been
      traditionally associated with a range of pathologies. It is now believed,
      however, that at basal levels these molecules also have a beneficial cellular
      function in the form of cell signaling and redox regulation. Critical to
      elucidating their physiological role is the opportunity to visualize and quantify
      the production of ROS with spatiotemporal accuracy. Armed with a newly developed,
      extremely sensitive fluorogenic alpha-tocopherol analogue (H4BPMHC), we report
      herein the observation of steady concentrations of lipid peroxyl radicals
      produced in live cell imaging conditions. Imaging studies with H4BPMHC indicate
      that the rate of production of lipid peroxyl radicals in HeLa cells under basal
      conditions is 33 nM/h within the cell. Our work further provides indisputable
      evidence on the antioxidant role of Vitamin E, as lipid peroxidation was
      suppressed in HeLa cells both under basal conditions and in the presence of Haber
      Weiss chemistry, generated by the presence of cumyl hydroperoxide and Cu2+ in
      solution, when supplemented with the alpha-tocopherol surrogate, PMHC (2,2,5,7,8
      pentamethyl-6-hydroxy-chromanol, an alpha-tocopherol analogue lacking the phytyl
      tail). H4BPMHC has the sensitivity needed to detect trace changes in oxidative
      status within the lipid membrane, underscoring the opportunity to illuminate the
      physiological relevance of lipid peroxyl radical production during cell
      homeostasis and disease.

PMID- 29043788
TI  - Molecular Road Map to Tuning Ground State Absorption and Excited State Dynamics
      of Long-Wavelength Absorbers.
AB  - Realizing chromophores that simultaneously possess substantial near-infrared
      (NIR) absorptivity and long-lived, high-yield triplet excited states is vital for
      many optoelectronic applications, such as optical power limiting and triplet
      triplet annihilation photon upconversion (TTA-UC). However, the energy gap law
      ensures such chromophores are rare, and molecular engineering of absorbers having
      such properties has proven challenging. Here, we present a versatile methodology
      to tackle this design issue by exploiting the ethyne-bridged
      (polypyridyl)metal(II) (M; M = Ru, Os)-(porphinato)metal(II) (PM'; M' = Zn, Pt,
      Pd) molecular architecture (M-(PM')n-M), wherein high-oscillator-strength NIR
      absorptivity up to 850 nm, near-unity intersystem crossing (ISC) quantum yields
      (PhiISC), and triplet excited-state (T1) lifetimes on the microseconds time scale
      are simultaneously realized. By varying the extent to which the atomic
      coefficients of heavy metal d orbitals contribute to the one-electron excitation
      configurations describing the initially prepared singlet and triplet excited
      state wave functions, we (i) show that the relative magnitudes of fluorescence
      (k0F), S1 -> S0 nonradiative decay (knr), S1 -> T1 ISC (kISC), and T1 -> S0
      relaxation (kT1->S0) rate constants can be finely tuned in M-(PM')n-M compounds
      and (ii) demonstrate designs in which the kISC magnitude dominates singlet
      manifold relaxation dynamics but does not give rise to T1 -> S0 conversion
      dynamics that short-circuit a microseconds time scale triplet lifetime. Notably,
      the NIR spectral domain absorptivities of M-(PM')n-M chromophores far exceed
      those of classic coordination complexes and organic materials possessing
      similarly high yields of triplet-state formation: in contrast to these benchmark
      materials, this work demonstrates that these M-(PM')n-M systems realize near unit
      PhiISC at extraordinarily modest S1-T1 energy gaps (~0.25 eV). This study
      underscores the photophysical diversity of the M-(PM')n-M platform and presents a
      new library of long-wavelength absorbers that efficiently populate long-lived T1
      states.

PMID- 29043789
TI  - Light-driven Hydrogen Evolution from Water by a Tripodal Silane Based CoII6L18
      Octahedral Cage.
AB  - The octahedral cage assembly [CoII6L18Cl6(H2O)6]Cl6 has been synthesized in a
      single-step reaction by using a polypyridyl-functionalized tripodal silane
      ligand. The electrochemical behavior of the cage in water exhibits the pH
      dependence of potential as well as catalytic current indicating the possible
      involvement of proton-coupled electron transfer in H2 evolution. Electrocatalytic
      hydrogen evolution from an aqueous buffered solution gave a turnover frequency of
      16 h-1. Further, this cage assembly has been explored as a photocatalyst (blue
      light irradiation lambda 469 nm) for the evolution of H2 from water in the
      presence of Ru(bpy)32+ as a photosensitizer and ascorbic acid as a sacrificial
      electron donor. This catalytic reaction is found to be pseudo first order with a
      turnover frequency of 20.50 h-1.

PMID- 29043792
TI  - Rates of Cr(VI) Generation from CrxFe1-x(OH)3 Solids upon Reaction with Manganese
      Oxide.
AB  - The reaction of manganese oxides with Cr(III)-bearing solids in soils and
      sediments can lead to the natural production of Cr(VI) in groundwater. Building
      on previous knowledge of MnO2 as an oxidant for Cr(III)-containing solids, this
      study systematically evaluated the rates and mechanisms of the oxidation of
      Cr(III) in iron oxides by delta-MnO2. The Fe/Cr ratio (x = 0.055-0.23 in CrxFe1
      x(OH)3) and pH (5-9) greatly influenced the Cr(VI) production rates by
      controlling the solubility of Cr(III) in iron oxides. We established a
      quantitative relationship between Cr(VI) production rates and Cr(III) solubility
      of CrxFe1-x(OH)3, which can help predict Cr(VI) production rates at different
      conditions. The adsorption of Cr(VI) and Mn(II) on solids shows a typical pH
      dependence for anions and cations. A multichamber reactor was used to assess the
      role of solid-solid contact in CrxFe1-x(OH)3-MnO2 interactions, which eliminates
      the contact of the two solids while still allowing aqueous species transport
      across a permeable membrane. Cr(VI) production rates were much lower in
      multichamber than in completely mixed batch experiments, indicating that the
      redox interaction is accelerated by mixing of the solids. Our results suggest
      that soluble Cr(III) released from CrxFe1-x(OH)3 solids to aqueous solution can
      migrate to MnO2 surfaces where it is oxidized.

PMID- 29043791
TI  - Lyophilized Engineered Phages for Escherichia coli Detection in Food Matrices.
AB  - Ease of use, low cost, and convenient transport are the key requirements for a
      commercial bacteria detection kit designed for resource-limited settings. Here,
      we report the colorimetric detection of Escherichia coli (E. coli) in food
      samples using freeze-dried engineered bacteriophages (phages). In this approach,
      we have engineered T7 phages to carry the lacZ operon driven by T7 promoter to
      overexpress reporter enzymes. The engineered phages were freeze-dried in a water
      soluble polymer for storage and transportation. When used for the detection of E.
      coli cells, the intracellular enzyme [beta-galactosidase (beta-gal)] was
      overexpressed and released into the surrounding media, providing an enzyme
      amplified colorimetric signal. Using this strategy, we were able to detect E.
      coli cells at the concentration of 102 CFU mL-1 in food samples without the need
      for sophisticated instruments or skilled operators.

PMID- 29043790
TI  - Emissive Synthetic Cofactors: An Isomorphic, Isofunctional, and Responsive NAD+
      Analogue.
AB  - The synthesis, photophysics, and biochemical utility of a fluorescent NAD+
      analogue based on an isothiazolo[4,3-d]pyrimidine core (NtzAD+) are described.
      Enzymatic reactions, photophysically monitored in real time, show NtzAD+ and
      NtzADH to be substrates for yeast alcohol dehydrogenase and lactate
      dehydrogenase, respectively, with reaction rates comparable to that of the native
      cofactors. A drop in fluorescence is seen as NtzAD+ is converted to NtzADH,
      reflecting a complementary photophysical behavior to that of the native
      NAD+/NADH. NtzAD+ and NtzADH serve as substrates for NADase, which selectively
      cleaves the nicotinamide's glycosidic bond yielding tzADP-ribose. NtzAD+ also
      serves as a substrate for ribosyl transferases, including human adenosine ribosyl
      transferase 5 (ART5) and Cholera toxin subunit A (CTA), which hydrolyze the
      nicotinamide and transfer tzADP-ribose to an arginine analogue, respectively.
      These reactions can be monitored by fluorescence spectroscopy, in stark contrast
      to the corresponding processes with the nonemissive NAD+.

PMID- 29043793
TI  - Hexagonally Ordered Arrays of alpha-Helical Bundles Formed from Peptide-Dendron
      Hybrids.
AB  - Combining monodisperse building blocks that have distinct folding properties
      serves as a modular strategy for controlling structural complexity in
      hierarchically organized materials. We combine an alpha-helical bundle-forming
      peptide with self-assembling dendrons to better control the arrangement of
      functional groups within cylindrical nanostructures. Site-specific grafting of
      dendrons to amino acid residues on the exterior of the alpha-helical bundle
      yields monodisperse macromolecules with programmable folding and self-assembly
      properties. The resulting hybrid biomaterials form thermotropic columnar
      hexagonal mesophases in which the peptides adopt an alpha-helical conformation.
      Bundling of the alpha-helical peptides accompanies self-assembly of the peptide
      dendron hybrids into cylindrical nanostructures. The bundle stoichiometry in the
      mesophase agrees well with the size found in solution for alpha-helical bundles
      of peptides with a similar amino acid sequence.

PMID- 29043794
TI  - Dynamic Transition from alpha-Helices to beta-Sheets in Polypeptide Coiled-Coil
      Motifs.
AB  - We carried out dynamic force manipulations in silico on a variety of coiled-coil
      protein fragments from myosin, chemotaxis receptor, vimentin, fibrin, and
      phenylalanine zippers that vary in size and topology of their alpha-helical
      packing. When stretched along the superhelical axis, all superhelices show
      elastic, plastic, and inelastic elongation regimes and undergo a dynamic
      transition from the alpha-helices to the beta-sheets, which marks the onset of
      plastic deformation. Using the Abeyaratne-Knowles formulation of phase
      transitions, we developed a new theoretical methodology to model mechanical and
      kinetic properties of protein coiled-coils under mechanical nonequilibrium
      conditions and to map out their energy landscapes. The theory was successfully
      validated by comparing the simulated and theoretical force-strain spectra. We
      derived the scaling laws for the elastic force and the force for alpha-to-beta
      transition, which can be used to understand natural proteins' properties as well
      as to rationally design novel biomaterials of required mechanical strength with
      desired balance between stiffness and plasticity.

PMID- 29043795
TI  - Small Microbial Three-Electrode Cell Based Biosensor for Online Detection of
      Acute Water Toxicity.
AB  - The monitoring of toxicity of water is very important to estimate the safety of
      drinking water and the level of water pollution. Herein, a small microbial three
      electrode cell (M3C) biosensor filled with polystyrene particles was proposed for
      online monitoring of the acute water toxicity. The peak current of the biosensor
      related with the performance of the bioanode was regarded as the toxicity
      indicator, and thus the acute water toxicity could be determined in terms of
      inhibition ratio by comparing the peak current obtained with water sample to that
      obtained with nontoxic standard water. The incorporation of polystyrene particles
      in the electrochemical cell not only reduced the volume of the samples used, but
      also improved the sensitivity of the biosensor. Experimental conditions including
      washing time with PBS and the concentration of sodium acetate solution were
      optimized. The stability of the M3C biosensor under optimal conditions was also
      investigated. The M3C biosensor was further examined by formaldehyde at the
      concentration of 0.01%, 0.03%, and 0.05% (v/v), and the corresponding inhibition
      ratios were 14.6%, 21.6%, and 36.4%, respectively. This work provides a new
      insight into the development of an online toxicity detector based on M3C
      biosensor.

PMID- 29043796
TI  - Composite Hydrogels Containing Bioactive Microreactors for Optical Enzymatic
      Lactate Sensing.
AB  - Continuously monitoring specific biomarkers offer a promising method to
      interrogate disease status and progression. In this work we have demonstrated a
      composite hydrogel-based sensing platform that may be used for optical detection
      of lactate. The sensor design consists of microsized enzymatic sensors that are
      embedded in an outer hydrogel matrix. In these engineered microdomains,
      encapsulated lactate oxidase serves as the bioactive component, phosphorescent
      metalloporphyrin acts as the optical transducer, and polyelectrolyte multilayers
      coated on the enzymatic microsensors control the permeation of lactate into the
      microsensors. The response of the composite hydrogel-based lactate sensors was
      characterized by subjecting the sensors to lactate concentration challenges at
      low physiological oxygen levels. The analytical range and the mean sensitivity
      were determined to be 9.2 +/- 0.83 mg/dL and 11 +/- 0.90% dL mg-1, respectively.
      Repeated cyclic exposure to high levels of lactate revealed that these sensors
      were extremely stable, with no significant loss in sensor response after 20
      cycles. These preliminary results support the premise that these composite
      hydrogels are capable of continuous lactate tracking and have the potential for
      use as fully implantable optical lactate sensors.

PMID- 29043797
TI  - Metal Oxides in Surface Sediment Control Nickel Bioavailability to Benthic
      Macroinvertebrates.
AB  - In aquatic ecosystems, the cycling and toxicity of nickel (Ni) are coupled to
      other elemental cycles that can limit its bioavailability. Current sediment risk
      assessment approaches consider acid-volatile sulfide (AVS) as the major binding
      phase for Ni, but have not yet incorporated ligands that are present in oxic
      sediments. Our study aimed to assess how metal oxides play a role in Ni
      bioavailability in surficial sediments exposed to effluent from two mine sites.
      We coupled spatially explicit sediment geochemistry (i.e., separate oxic and
      suboxic) to the indigenous macroinvertebrate community structure. Effluent
      exposed sites contained high concentrations of sediment Ni and AVS, though
      roughly 80% less AVS was observed in surface sediments. Iron (Fe) oxide mineral
      concentrations were elevated in surface sediments and bound a substantial
      proportion of Ni. Redundancy analysis of the invertebrate community showed
      surface sediment geochemistry significantly explained shifts in community
      abundances. Relative abundance of the dominant mayfly (Ephemeridae) was reduced
      in sites with greater bioavailable Ni, but accounting for Fe oxide-bound Ni
      greatly decreased variation in effect thresholds between the two mine sites. Our
      results provide field-based evidence that solid-phase ligands in oxic sediment,
      most notably Fe oxides, may have a critical role in controlling nickel
      bioavailability.

PMID- 29043798
TI  - Jozilebomines A and B, Naphthylisoquinoline Dimers from the Congolese Liana
      Ancistrocladus ileboensis, with Antiausterity Activities against the PANC-1 Human
      Pancreatic Cancer Cell Line.
AB  - Two new naphthylisoquinoline dimers, jozilebomines A (1a) and B (1b), were
      isolated from the roots of the Congolese plant Ancistrocladus ileboensis, along
      with the known dimer jozimine A2 (2). These compounds are Dioncophyllaceae-type
      metabolites, i.e., lacking oxygen functions at C-6 and with an R-configuration at
      C-3 in their tetrahydroisoquinoline moieties. The dimers 1a and 1b consist of two
      7,1'-coupled naphthylisoquinoline monomers linked through an unprecedented 3',6"
      coupling in the binaphthalene core and not, as in 2, via the C-3-positions of the
      two naphthalene units. Thus, different from the C2-symmetric jozimine A2 (2), the
      new jozilebomines are constitutionally unsymmetric. The central biaryl axis of
      each of the three dimers is rotationally hindered, so that 1a, 1b, and 2 possess
      three consecutive chiral axes. The two jozilebomines have identical constitutions
      and the same absolute configurations at all four stereogenic centers, but differ
      from each other in their axial chirality. Their structural elucidation was
      achieved by HRESIMS, 1D and 2D NMR, oxidative degradation, and experimental and
      calculated ECD data. They exhibited distinct and specific antiplasmodial
      activities. All dimers showed potent cytotoxicity against HeLa human cervical
      cancer cells and preferential cytotoxicity against PANC-1 human pancreatic cancer
      cells under nutrition-deprived conditions. Furthermore, these dimers
      significantly inhibited the colony formation of PANC-1 cells, even when exposed
      to noncytotoxic concentration for a short time. Jozilebomines A (1a) and B (1b)
      and jozimine A2 (2) represent novel potential candidates for future drug
      development against pancreatic cancer.

PMID- 29043799
TI  - Influence of the Trans/Cis Conformer Ratio on the Stereoselectivity of Peptidic
      Catalysts.
AB  - Trans/cis isomerization of Xaa-Pro bonds is key for the structure and function of
      several enzymes. In recent years, numerous versatile peptidic catalysts have been
      developed that bear Xaa-Pro amide bonds. Due to the many degrees of freedom
      within even short peptides, the design and optimization of peptidic catalysts by
      rational structural modifications is difficult. We envisioned that control over
      the trans/cis amide bond ratio may provide a tool to optimize the catalytic
      performance of peptidic catalysts. Here, we investigated the influence of the
      amide bond conformation on the stereoselectivity of H-Pro-Pro-Xaa-NH2-type
      peptidic catalysts in conjugate addition reactions. The middle Pro residue within
      the tripeptides was replaced with analogues of varying ring sizes (azetidine
      carboxylic acid, Aze, and piperidine carboxylic acid, Pip) to produce different
      trans/cis ratios in different solvents. The studies revealed a direct correlation
      between the trans/cis amide bond ratio and the enantio- and diastereoselectivity
      of structurally related peptidic catalysts. These insights led to the
      identification of H-d-Pro-Pip-Glu-NH2 as a highly reactive and stereoselective
      amine-based catalyst that allows C-C bond formations to be performed in the
      presence of as little as 0.05 mol %, which is the lowest catalyst loading yet
      achieved for organocatalyzed reactions that rely on an enamine-based mechanism.

PMID- 29043800
TI  - Stabilization of the Cubic Crystalline Phase in Organometal Halide Perovskite
      Quantum Dots via Surface Energy Manipulation.
AB  - Surface functionalization of nanoscale materials has a significant impact on
      their properties. We have demonstrated the effect of different passivating
      ligands on the crystal phase of organometal halide perovskite quantum dots
      (PQDs). Using static and dynamic spectroscopy, we studied phase transitions in
      CH3NH3PbBr3 PQDs ligated with either octylaminebromide (P-OABr) or 3-aminopropyl
      triethoxysilane (P-APTES). Around 140 K, P-OABr underwent a structural phase
      transition from tetragonal to orthorhombic, established by the emergence of a
      higher energy band in the photoluminescence (PL) spectrum. This was not observed
      in P-APTES, despite cooling down to 20 K. Additionally, time-resolved and
      excitation power-dependent PL, as well as Raman spectroscopy over a range of 300
      20 K, revealed that recombination rates and types of charge carriers involved are
      significantly different in P-APTES and P-OABr. Our findings highlight how aspects
      of PQD phase stabilization are linked to nanoscale morphology and the crystal
      phase diagram.

PMID- 29043801
TI  - Compressibility Anomalies in Stretched Water and Their Interplay with Density
      Anomalies.
AB  - Water keeps puzzling scientists because of its numerous properties which behave
      oppositely to those of usual liquids: for instance, water expands upon cooling,
      and liquid water is denser than ice. To explain this anomalous behavior, several
      theories have been proposed, with different predictions for the properties of
      supercooled water (liquid at conditions where ice is stable). However,
      discriminating between those theories with experiments has remained elusive
      because of spontaneous ice nucleation. Here we measure the sound velocity in
      liquid water stretched to negative pressure and derive an experimental equation
      of state, which reveals compressibility anomalies. We show by rigorous
      thermodynamic relations how these anomalies are intricately linked with the
      density anomaly. Some features we observe are necessary conditions for the
      validity of two theories of water.

PMID- 29043802
TI  - Sporothriolide-Related Compounds from the Fungus Hypoxylon monticulosum CLL-205
      Isolated from a Sphaerocladina Sponge from the Tahiti Coast.
AB  - Two sporothriolide-related compounds were obtained from an extract of the fungus
      Hypoxylon monticulosum CLL-205, isolated from a Sphaerocladina sponge collected
      from the Tahiti coast. Compound 2 is a deoxy analogue of sporothric acid (4).
      Compound 3 is a newly reported unusual scaffold combining sporothriolide (1) and
      trienylfuranol A (5) moieties, through a Diels-Alderase-type reaction. Various
      experimental and analytical arguments supported the biocatalytic origin of
      compound 3. The structures of the isolated compounds were elucidated using 1D and
      2D NMR, HRMS, and IR data. The structure and the absolute configuration of 3 were
      unambiguously confirmed by a single-crystal X-ray diffraction analysis.

PMID- 29043803
TI  - Identification of Privileged Antichlamydial Natural Products by a Ligand-Based
      Strategy.
AB  - The obligate intracellular pathogen Chlamydia pneumoniae remains a difficult
      target for antimicrobial therapy. Owing to the permeability barrier placed by
      bacterial and host vacuolar membranes, as well as the propensity of the bacterium
      for persistent infections, treatment failures are common. Despite the urgent need
      for new antichlamydial compounds, their discovery is challenged by the
      technically demanding assay procedures and lack of validated targets. An
      alternative strategy of using naturally occurring compounds and their derivatives
      against C. pneumoniae is presented. The strategy consists of the application of
      ligand-based virtual screening to a natural product library of 502 compounds with
      the ChemGPS-NP chemography tool followed by in vitro antichlamydial assays. The
      reference set used for the 2D similarity search was constructed of 19 known
      antichlamydial compounds of plant origin. Based on the similarity screen, 53
      virtual hits were selected for in vitro testing. Six compounds (leads) were
      identified that cause >=50% C. pneumoniae growth inhibition and showed no impact
      on host cell viability. The leads fall into completely new antichlamydial
      chemotypes, one of them being mycophenolic acid (IC50 value 0.3 MUM). The outcome
      indicates that using this flipped, target-independent strategy is useful for
      facilitating the antimicrobial lead discovery against challenging microbes.

PMID- 29043804
TI  - Proton-Assisted Recoupling (PAR) in Peptides and Proteins.
AB  - Proton-assisted recoupling (PAR) is examined by exploring optimal experimental
      conditions and magnetization transfer rates in a variety of biologically relevant
      nuclear spin-systems, including simple amino acids, model peptides, and two
      proteins-nanocrystalline protein G (GB1), and importantly amyloid beta 1-42
      (M0Abeta1-42) fibrils. A selective PAR protocol, SUBPAR (setting up better proton
      assisted recoupling), is described to observe magnetization transfer in one
      dimensional spectra, which minimizes experiment time (in comparison to two
      dimensional experiments) and thereby enables an efficient assessment of optimal
      PAR conditions for a desired magnetization transfer. In the case of the peptide
      spin systems, experimental and simulated PAR data sets are compared on a
      semiquantitative level, thereby elucidating the interactions influencing PAR
      magnetization transfer and their manifestations in different spin transfer
      networks. Using the optimum Rabi frequencies determined by SUBPAR, PAR
      magnetization transfer trajectories (or buildup curves) were recorded and
      compared to simulated results for short peptides. PAR buildup curves were also
      recorded for M0Abeta1-42 and examined conjointly with a recent structural model.
      The majority of salient cross-peak intensities observed in the M0Abeta1-42 PAR
      spectra are well-modeled with a simple biexponential equation, although the
      fitting parameters do not show any strong correlation to internuclear distances.
      Nevertheless, these parameters provide a wealth of invaluable semiquantitative
      structural constraints for the M0Abeta1-42. The results presented here offer a
      complete protocol for recording PAR 13C-13C correlation spectra with high
      efficiency and using the resulting information in protein structural studies.

PMID- 29043805
TI  - Mitogen-Activated Protein Kinase Kinase 5 Regulates Proliferation and
      Biosynthetic Processes in Procyclic Forms of Trypanosoma brucei.
AB  - The pathogenic protozoan T. brucei alternates into distinct developmental stages
      in the mammalian and insect hosts. The mitogen-activated protein kinase (MAPK)
      signaling pathways transduce extracellular stimuli into a range of cellular
      responses, which ultimately lead to the adaptation to the external environment.
      Here, we combined a loss of function approach with stable isotope labeling with
      amino acids in cell culture (SILAC)-based mass spectrometry (MS) to investigate
      the role of the mitogen-activated protein kinase kinase 5 (MKK5) in T. brucei.
      The silencing of MKK5 significantly decreased the proliferation of procyclic
      forms of T. brucei. To shed light on the molecular alterations associated with
      this phenotype, we measured the total proteome and phosphoproteome of cells
      silenced for MKK5. In the total proteome, we observed a general decrease in
      proteins related to ribosome and translation as well as down-regulation of
      several components of the fatty acids biosynthesis pathway. In addition, we
      observed alterations in the protein levels and phosphorylation of key metabolic
      enzymes, which point toward a suppression of the oxidative metabolism. Taken
      together, our findings show that the silencing of MKK5 alters cell growth, energy
      metabolism, protein and fatty acids biosynthesis in procyclic T. brucei.

PMID- 29043806
TI  - High Hole-Mobility Molecular Layer Made from Strong Electron Acceptor Molecules
      with Metal Adatoms.
AB  - The electronic structure of 7,7,8,8-tetracyanoquinodimethane (TCNQ) and 2,3,5,6
      tetrafluoro-TCNQ (F4TCNQ) monolayers on Au(111) has been investigated by means of
      angle-resolved photoemission spectroscopy (ARPES) with synchrotron radiation. In
      contrast to the physisorbed TCNQ/Au(111) interface, the high-resolution core
      level photoemission spectra and the low-energy electron diffraction at the
      F4TCNQ/Au(111) interface show evidence for the strong charge transfer (CT) from
      Au to F4TCNQ and for the Au atom segregation from the underlying Au(111) surface,
      suggesting a possible origin of the spontaneous formation of the two-dimensional
      F4TCNQ-Au network. The ARPES experiment reveals a low hole-injection barrier and
      large band dispersion in the CT-induced topmost valence level of the F4TCNQ-Au
      network with 260 meV bandwidth due to the adatom-mediated intermolecular
      interaction. These results indicate that strong electron acceptor molecules with
      metal adatoms can form high hole-mobility molecular layers by controlling the
      molecule-metal ordered structure and their CT interaction.

PMID- 29043807
TI  - 2,3-Dihydro-3beta-methoxy Withaferin-A Protects Normal Cells against Stress:
      Molecular Evidence of Its Potent Cytoprotective Activity.
AB  - 2,3-Dihydro-3beta-methoxy withaferin-A (3betamWi-A) is a natural withanolide that
      is structurally close to withaferin-A (Wi-A), is cytotoxic to human cancer cells,
      and is a candidate anticancer natural compound. Using cell-based biochemical,
      molecular, and imaging assays, we report that Wi-A and 3betamWi-A possess
      contrasting activities. Whereas Wi-A caused oxidative stress to normal cells,
      3betamWi-A was well tolerated at even 10-fold higher concentrations. Furthermore,
      it promoted survival and protected normal cells against oxidative, UV radiation,
      and chemical stresses. We provide molecular evidence that 3betamWi-A induces
      antistress and pro-survival signaling through activation of the pAkt/MAPK
      pathway. We demonstrate that 3betamWi-A (i) contrary to Wi-A is safe and
      possesses stress-relieving activity, (ii) when given subsequent to a variety of
      stress factors including Wi-A, protects normal cells against their toxicity, and
      (iii) is a vital compound that may guard normal cells against the toxicity
      associated with various targeted therapeutic regimes in clinical practice.

PMID- 29043808
TI  - Cobalt-Catalyzed Oxidative Cyclization of Benzamides with Maleimides: Synthesis
      of Isoindolone Spirosuccinimides.
AB  - The oxidative cyclization of substituted benzamides with maleimides assisted by 8
      aminoquinoline in the presence of a catalytic amount of Co(OAc)2.4H2O provides
      isoindolone spirosuccinimides in good to excellent yields. The cyclization
      reaction was compatible with various substituted benzamides and maleimides. A
      possible reaction mechanism involving the C-H bond activation as a key step was
      proposed. The competition experiment and deuterium labeling studies were
      performed to investigate the mechanism of the reaction.

PMID- 29043809
TI  - Adsorption at the Air-Water Interface in Biosurfactant-Surfactant Mixtures:
      Quantitative Analysis of Adsorption in a Five-Component Mixture.
AB  - The composition of the air-water adsorbed layer of a quinary mixture consisting
      of three conventional surfactants, octaethylene glycol monododecyl ether (C12E8),
      dodecane-6-p-sodium benzene sulfonate (LAS6), and diethylene glycol monododecyl
      ether sodium sulfate (SLE2S), mixed with two biosurfactants, the rhamnolipids l
      rhamnosyl-l-rhamnosyl-beta-hydroxydecanoyl-beta-hydroxydecanoyl, R2, and l
      rhamnosyl-beta-hydroxydecanoyl-beta-hydroxydecanoyl, R1, has been measured over a
      range of compositions above the mixed critical micelle concentration. Additional
      measurements on some of the subsets of ternary and binary mixtures have also been
      measured by NR. The results have been analyzed using the pseudophase
      approximation (PPA) in conjunction with an excess free energy, GE, that depends
      on the quadratic and cubic terms in the composition. The compositions of the
      binary, ternary, and quinary mixtures could all be fitted to two sets of
      interaction parameters between the pairs of surfactants, one for micelles and one
      for adsorption. No ternary interactions or ternary corrections were required.
      Because the system contains two strongly anionic surfactants, the PPA can be
      extended, in practice, to ionic surfactants, contrary to the prevailing view. The
      values of the interaction parameters show that the quinary mixture, SLE2S-LAS6
      C12E8-R1-R2, which is known to be a highly effective surfactant system, is
      characterized by a sequence of strong surface but weak micellar interactions.
      About half of the minima in GE for the strong surface interactions occur well
      away from the regular solution value of 0.5.

PMID- 29043810
TI  - Structure and Thermodynamics of Metal Clusters on Atomically Smooth Substrates.
AB  - We analyze the structure of model NiN and CuN clusters (N = 55, 147) supported on
      a variety of atomically smooth van der Waals surfaces. The global minima are
      mapped in the space of two parameters: (i) the laterally averaged surface
      stickiness, gamma, which controls the macroscopic wetting angle, and (ii) the
      surface microstructure, which produces more subtle but important templating via
      epitaxial stresses. We find that adjusting the substrate lattice (even at
      constant gamma) can favor different crystal plane orientations in the cluster,
      stabilize hexagonal close-packed order, or induce various defects, such as
      stacking faults, twin boundaries, and five-fold disclinations. Thermodynamic
      analysis reveals substrate-dependent solid-solid transitions in cluster
      morphology, with tunable transition temperature and sometimes exhibiting re
      entrant behavior. These results shed new light on the extent to which a
      supporting surface can be used to influence the equilibrium behavior of
      nanoparticles.

PMID- 29043811
TI  - Investigation of the Intra- and Interlaboratory Reproducibility of a Small Scale
      Standardized Supersaturation and Precipitation Method.
AB  - The high number of poorly water-soluble compounds in drug development has
      increased the need for enabling formulations to improve oral bioavailability. One
      frequently applied approach is to induce supersaturation at the absorptive site,
      e.g., the small intestine, increasing the amount of dissolved compound available
      for absorption. However, due to the stochastic nature of nucleation,
      supersaturating drug delivery systems may lead to inter- and intrapersonal
      variability. The ability to define a feasible range with respect to the
      supersaturation level is a crucial factor for a successful formulation.
      Therefore, an in vitro method is needed, from where the ability of a compound to
      supersaturate can be defined in a reproducible way. Hence, this study
      investigates the reproducibility of an in vitro small scale standardized
      supersaturation and precipitation method (SSPM). First an intralaboratory
      reproducibility study of felodipine was conducted, after which seven partners
      contributed with data for three model compounds; aprepitant, felodipine, and
      fenofibrate, to determine the interlaboratory reproducibility of the SSPM. The
      first part of the SSPM determines the apparent degrees of supersaturation (aDS)
      to investigate for each compound. Each partner independently determined the
      maximum possible aDS and induced 100, 87.5, 75, and 50% of their determined
      maximum possible aDS in the SSPM. The concentration-time profile of the
      supersaturation and following precipitation was obtained in order to determine
      the induction time (tind) for detectable precipitation. The data showed that the
      absolute values of tind and aDS were not directly comparable between partners,
      however, upon linearization of the data a reproducible rank ordering of the three
      model compounds was obtained based on the beta-value, which was defined as the
      slope of the ln(tind) versus ln(aDS)-2 plot. Linear regression of this plot
      showed that aprepitant had the highest beta-value, 15.1, while felodipine and
      fenofibrate had comparable beta-values, 4.0 and 4.3, respectively. Of the five
      partners contributing with full data sets, 80% could obtain the same rank order
      for the three model compounds using the SSPM (aprepitant > felodipine ~
      fenofibrate). The alpha-value is dependent on the experimental setup and can be
      used as a parameter to evaluate the uniformity of the data set. This study
      indicated that the SSPM was able to obtain the same rank order of the beta-value
      between partners and, thus, that the SSPM may be used to classify compounds
      depending on their supersaturation propensity.

PMID- 29043813
TI  - Catalyst Selection Facilitates the Use of Heterocyclic Sulfinates as General
      Nucleophilic Coupling Partners in Palladium-Catalyzed Coupling Reactions.
AB  - A range of 5- and 6-membered heterocycle-derived sulfinates are shown to be
      effective nucleophilic coupling partners with aryl chlorides and bromides using
      Pd(0) catalysis. The use of optimal reaction conditions, specifically
      incorporating a P(t-Bu)2Me-derived Pd catalyst, allowed reactions to be performed
      at moderate temperatures and enabled the inclusion of a variety of sensitive
      functional groups. Challenging heterocyclic sulfinates, including pyrazine,
      pyridazine, pyrimidine, pyrazole, and imidazole, were all shown to perform well.

PMID- 29043812
TI  - Amphiphilic Modulation of Glycosylated Antitumor Ether Lipids Results in a Potent
      Triamino Scaffold against Epithelial Cancer Cell Lines and BT474 Cancer Stem
      Cells.
AB  - The problems of resistance to apoptosis-inducing drugs, recurrence, and
      metastases that have bedeviled cancer treatment have been attributed to the
      presence of cancer stem cells (CSCs) in tumors, and there is currently no
      clinically indicated drug for their eradication. We previously reported that
      glycosylated antitumor ether lipids (GAELs) display potent activity against CSCs.
      Here, we show that by carefully modulating the amphiphilic nature of a monoamine
      based GAEL, we can generate a potent triamino scaffold that is active against a
      panel of hard-to-kill epithelial cancer cell lines (including triple-negative
      breast) and BT474 CSCs. The most active compound of this set, which acts via a
      nonmembranolytic, nonapoptotic caspase-independent mechanism, is more effective
      than cisplatin and doxorubicin against these cell lines and more potent than
      salinomycin against BT474 CSCs. Understanding the combination of factors crucial
      for the enhanced cytotoxicity of GAELs opens new avenues to develop potent
      compounds against drug-resistant cancer cells and CSCs.

PMID- 29043814
TI  - Boronic Acid Accelerated Three-Component Reaction for the Synthesis of alpha
      Sulfanyl-Substituted Indole-3-acetic Acids.
AB  - Boronic acid was used to accelerate a three-component reaction of indoles,
      thiols, and glyoxylic acids for the synthesis of alpha-sulfanyl-substituted
      indole-3-acetic acids. Boronic acid catalysis to activate the alpha-hydroxy group
      in alpha-hydroxycarboxylic acid intermediates and intramolecular assistance by
      free carboxylic acid were the keys to accelerating the product formation.

PMID- 29043815
TI  - Graphene as Barrier to Prevent Volume Increment of Air Bubbles over Silicone
      Polymer in Aqueous Environment.
AB  - The interaction of air bubbles with surfaces immersed in water is of fundamental
      importance in many fields of application ranging from energy to biology. However,
      many aspects of this topic such as the stability of surfaces in contact with
      bubbles remain unexplored. For this reason, in this work, we investigate the
      interaction of air bubbles with different kinds of dispersive surfaces immersed
      in water. The surfaces studied were polydimethylsiloxane (PDMS), graphite, and
      single layer graphene/PDMS composite. X-ray photoelectron spectroscopy (XPS)
      analysis allows determining the elemental surface composition, while Raman
      spectroscopy was used to assess the effectiveness of graphene monolayer transfer
      on PDMS. Atomic force microscopy (AFM) was used to study the surface modification
      of samples immersed in water. The surface wettability has been investigated by
      contact angle measurements, and the stability of the gas bubbles was determined
      by captive contact angle (CCA) measurements. CCA measurements show that the air
      bubble on graphite surface exhibits a stable behavior while, surprisingly, the
      volume of the air bubble on PDMS increases as a function of immersion time
      (bubble dynamic evolution). Indeed, the air bubble volume on the PDMS rises by
      increasing immersion time in water. The experimental results indicate that the
      dynamic evolution of air bubble in contact with PDMS is related to the
      rearrangement of surface polymer chains via the migration of the polar groups. On
      the contrary, when a graphene monolayer is present on PDMS, it acts as an
      absolute barrier suppressing the dynamic evolution of the bubble and preserving
      the optical transparency of PDMS.

PMID- 29043816
TI  - Axial Confocal Tomography of Capillary-Contained Colloidal Structures.
AB  - Confocal microscopy is widely used for three-dimensional (3D) sample
      reconstructions. Arguably, the most significant challenge in such reconstructions
      is posed by the resolution along the optical axis being significantly lower than
      in the lateral directions. In addition, the imaging rate is lower along the
      optical axis in most confocal architectures, prohibiting reliable 3D
      reconstruction of dynamic samples. Here, we demonstrate a very simple, cheap, and
      generic method of multiangle microscopy, allowing high-resolution high-rate
      confocal slice collection to be carried out with capillary-contained colloidal
      samples in a wide range of slice orientations. This method, realizable with any
      common confocal architecture and recently implemented with macroscopic specimens
      enclosed in rotatable cylindrical capillaries, allows 3D reconstructions of
      colloidal structures to be verified by direct experiments and provides a solid
      testing ground for complex reconstruction algorithms. In this paper, we focus on
      the implementation of this method for dense nonrotatable colloidal samples,
      contained in complex-shaped capillaries. Additionally, we discuss strategies to
      minimize potential pitfalls of this method, such as the artificial appearance of
      chain-like particle structures.

PMID- 29043817
TI  - Iridium/Bipyridine-Catalyzed ortho-Selective C-H Borylation of Phenol and Aniline
      Derivatives.
AB  - An iridium-catalyzed ortho-selective C-H borylation of phenol and aniline
      derivatives has been successfully developed. Iridium/bipyridine-catalyzed C-H
      borylation generally occurred at the meta- and para-positions of aromatic
      substrates. Introduction of an electron-withdrawing substituent on the bipyridine
      type ligand and a methylthiomethyl group on the hydroxy and amino groups of the
      phenol and aniline substrates, however, dramatically altered the
      regioselectivity, affording exclusively ortho-borylated products. The reaction
      proceeded in good to excellent yields with good functional group tolerance. C-H
      borylation was applied to the synthesis of a calcium receptor modulator.

PMID- 29043818
TI  - Toward the Elucidation of the Competing Role of Evaporation and Thermal
      Decomposition in Ionic Liquids: A Multitechnique Study of the Vaporization
      Behavior of 1-Butyl-3-methylimidazolium Hexafluorophosphate under Effusion
      Conditions.
AB  - The evaporation/decomposition behavior of the imidazolium ionic liquid 1-butyl-3
      methylimidazolium hexafluorophosphate (BMImPF6) was investigated in the overall
      temperature range 425-551 K by means of the molecular-effusion-based techniques
      Knudsen effusion mass loss (KEML) and Knudsen effusion mass spectrometry (KEMS),
      using effusion orifices of different size (from 0.2 to 3 mm in diameter).
      Specific effusion fluxes measured by KEML were found to depend markedly on the
      orifice size, suggesting the occurrence of a kinetically delayed
      evaporation/decomposition process. KEMS experiments revealed that other species
      are present in the vapor phase besides the intact ion pair BMImPF6(g) produced by
      the simple evaporation BMImPF6(l) = BMImPF6(g), with relative abundances
      depending on the orifice size-the larger the orifice, the larger the contribution
      of the BMImPF6(g) species. By combining KEML and KEMS results, the conclusion is
      drawn that in the investigated temperature range, when small effusion orifices
      are used, a significant part of the mass loss/volatility of BMImPF6 is due to
      molecular products formed by decomposition/dissociation processes rather than to
      evaporated intact ion pairs. Additional experiments performed by nonisothermal
      thermogravimetry-differential thermal analysis (TG-DTA) further support the
      evidence of simultaneous evaporation/decomposition, although the conventional
      decomposition temperature derived from TG curves is much higher than the
      temperatures covered in effusion experiments. Partial pressures of the BMImPF6(g)
      species were derived from KEMS spectra and analyzed by second- and third-law
      methods giving a value of DeltaevapH298K degrees  = 145.3 +/- 2.9 kJ.mol-1 for
      the standard evaporation enthalpy of BMImPF6. A comparison is done with the
      behavior of the 1-butyl-3-methylimidazolium bis(trifluoromethyl)sulfonylimide
      (BMImNTf2) ionic liquid.

PMID- 29043819
TI  - Silver-Catalyzed Minisci Reactions Using Selectfluor as a Mild Oxidant.
AB  - A new method for silver-catalyzed Minisci reactions using Selectfluor as a mild
      oxidant is reported. Heteroarenes and quinones both participate in radical C-H
      alkylation and arylation from a variety of carboxylic and boronic acid radical
      precursors. Several oxidatively sensitive and highly reactive radical species are
      successful, providing structures that are challenging to access by other means.

PMID- 29043820
TI  - Stable Isotope-Assisted Metabolic Profiling Reveals Growth Mode Dependent
      Differential Metabolism and Multiple Catabolic Pathways of l-Phenylalanine in
      Rubrivivax benzoatilyticus JA2.
AB  - Anoxygenic phototrophic bacteria are metabolically versatile and survive under
      different growth modes using diverse organic compounds, yet their metabolic
      diversity is largely unexplored. In the present study, we employed stable-isotope
      assisted metabolic profiling to unravel the l-phenylalanine catabolism in
      Rubrivivax benzoatilyticus JA2 under varying growth modes. Strain JA2 grows under
      anaerobic and aerobic conditions by utilizing l-phenylalanine as a nitrogen
      source. Furthermore, ring-labeled 13C6-phenylalanine feeding followed by liquid
      chromatography-mass spectrometry exometabolite profiling revealed 60 labeled
      metabolic features (M + 6, M + 12, and M + 18) derived solely from l
      phenylalanine, of which 11 were identified, 7 putatively identified, and 42
      unidentified under anaerobic and aerobic conditions. However, labeled metabolites
      were significantly higher in aerobic compared to anaerobic conditions.
      Furthermore, detected metabolites and enzyme activities indicated multiple l
      phenylalanine catabolic routes mainly Ehrlich, homogentisate-dependent melanin,
      benzenoid, and unidentified pathways operating under anaerobic and aerobic
      conditions in strain JA2. Interestingly, the study indicated l-phenylalanine
      dependent and independent benzenoid biosynthesis in strain JA2 and a differential
      flux of l-phenylalanine to Ehrlich and benzenoid pathways under anaerobic and
      aerobic conditions. Additionally, unidentified labeled metabolites strongly
      suggest the presence of unknown phenylalanine catabolic routes in strain JA2.
      Overall, the study uncovered the l-phenylalanine catabolic diversity in strain
      JA2 and demonstrated the potential of stable isotope-assisted metabolomics in
      unraveling the hidden metabolic repertoire.

PMID- 29043821
TI  - In Situ Generation of a Regio- and Diastereoselective Hydroaminoalkylation
      Catalyst Using Commercially Available Starting Materials.
AB  - The design of an easy to use catalyst system for the regio- and
      diastereoselective intermolecular hydroaminoalkylation of alkenes with secondary
      amines is reported. The method utilizes commercially available ligands and
      tantalum starting materials, and does not require the isolation of air and water
      sensitive organometallic complexes. The in situ prepared catalyst is active
      toward a variety of secondary amine substrates, including those with ethyl
      substituents which yield alpha- and beta-alkylated amines as a single
      diastereomer. This catalytic transformation can be used to prepare amines
      containing functionality that promotes ring closure to achieve the
      diastereoselective synthesis of di- and trialkylated N-heterocycles.

PMID- 29043822
TI  - Palladium-Catalyzed Asymmetric Allylic Alkylation of Alkyl-Substituted Allyl
      Reagents with Acyclic Amides.
AB  - A wide range of alkyl-substituted allyl reagents, as well as nonstabilized carbon
      nucleophiles, was successfully used for the first time in the palladium-catalyzed
      asymmetric allylic alkylation reaction, affording the corresponding allylic
      alkylated products in high yields with high enantioselectivities. The usefulness
      of the protocol has been demonstrated by the enantioselective synthesis of an
      important chiral building block and enantiomer of Dubiusamine A.

PMID- 29043824
TI  - Ferrofluid-Based Droplet Interface Bilayer Networks.
AB  - Droplet interface bilayer (DIB) networks allow for the construction of stimuli
      responsive, membrane-based materials. Traditionally used for studying cellular
      transport phenomena, the DIB technique has proven its practicality when creating
      structured droplet networks. These structures consist of aqueous compartments
      capable of exchanging their contents across membranous barriers in a regulated
      fashion via embedded biomolecules, thus approximating the activity of natural
      cellular systems. However, lipid bilayer networks are often static and incapable
      of any reconfiguration in their architecture. In this study, we investigate the
      incorporation of a magnetic fluid or ferrofluid within the droplet phases for the
      creation of magnetically responsive DIB arrays. The impact of adding ferrofluid
      to the aqueous phases of the DIB networks is assessed by examining the bilayers'
      interfacial tensions, thickness, and channel activity. Once compatibility is
      established, potential applications of the ferrofluid-enabled DIBs are showcased
      by remotely modifying membrane qualities through magnetic fields. Ferrofluids do
      not significantly alter the bilayers' properties or functionality and can
      therefore be safely embedded within the DIB platform, allowing for remote
      manipulation of the interfacial bilayer properties.

PMID- 29043825
TI  - Unconventional Current Scaling and Edge Effects for Charge Transport through
      Molecular Clusters.
AB  - Metal-molecule-metal junctions are the key components of molecular electronics
      circuits. Gaining a microscopic understanding of their conducting properties is
      central to advancing the field. In the present contribution, we highlight the
      fundamental differences between single-molecule and ensemble junctions focusing
      on the fundamentals of transport through molecular clusters. In this way, we
      elucidate the collective behavior of parallel molecular wires, bridging the gap
      between single molecule and large-area monolayer electronics, where even in the
      latter case transport is usually dominated by finite-size islands. On the basis
      of first-principles charge-transport simulations, we explain why the scaling of
      the conductivity of a junction has to be distinctly nonlinear in the number of
      molecules it contains. Moreover, transport through molecular clusters is found to
      be highly inhomogeneous with pronounced edge effects determined by molecules in
      locally different electrostatic environments. These effects are most pronounced
      for comparably small clusters, but electrostatic considerations show that they
      prevail also for more extended systems.

PMID- 29043826
TI  - ABO serology in a case of persistent weak A in a recipient following a group O
      matched unrelated bone marrow transplant.
AB  - CONCLUSIONS: HLA-matched hematopoietic stem cell transplantation (HSCT) from red
      blood cell (RBC)-incompatible donors is not uncommon. The engraftment process
      following ABO-incompatible allogeneic HSCT results in the transition from patient
      blood group to donor blood group in the recipient. In contrast, most non
      hematopoietic tissues retain expression of the patient's original blood group for
      life, and these antigens may adsorb from the plasma onto the donor-derived RBCs.
      Correct serologic interpretation of the ABO blood group during this engraftment
      process can be difficult. We present the serologic findings of a 15-year-old girl
      of Maori descent, who was diagnosed with acute myeloid leukemia and transplanted
      with an HLA-matched unrelated group O, D+ bone marrow. Despite engraftment, her
      RBCs showed persistence of weak A. This case report showcases the importance of
      awareness and correct serologic interpretation of weak persistence of recipient
      ABH substance on the patient's RBCs for clinical decision-making, blood component
      support, and patient wellbeing.

PMID- 29043827
TI  - Stability guidelines for dithiothreitol-treated red blood cell reagents used for
      antibody detection methods in patients treated with daratumumab.
AB  - CONCLUSIONS: Daratumumab (DARA), a drug used to treat patients with multiple
      myeloma, causes interference in pre-transfusion testing. Samples from patients
      receiving DARA exhibit panreactivity in antibody detection and identification
      tests with red blood cells (RBCs). Many hospitals are sending these samples to
      reference laboratories. Dithiothreitol (DTT), a sulfhydryl chemical treatment of
      RBCs, negates this reactivity. This study investigated the stability of the
      antigens on DTT-treated RBCs to determine if large quantities of RBCs could be
      treated at one time, stored, and used for testing at a later time. Panel cells
      were treated with DTT and then stored as three sets. Set 1 DTT-treated RBCs were
      stored in Alsever's solution at 2 degrees C to 8 degrees C, washed daily, and
      suspended in pH 7.3 phosphate-buffered saline (PBS) prior to antigen typing. Set
      2 DTT-treated RBCs were stored in pH 7.3 PBS. Set 3 DTT-treated RBCs were stored
      in Alsever's solution. Sets 2 and 3 were inspected daily for 14 days for
      observation of hemolysis. In Set 1, all antigen reactivity remained at >=2+ with
      both single- and double-dose cells for 14 days. The Rh antigens gave stronger
      reactions longer, compared with those tested in the Duffy, Kidd, and MNS blood
      group systems. Sets 2 and 3 were monitored for hemolysis. On day 3, Set 2 began
      displaying hemolysis, with complete hemolysis by day 8. Set 3 did not display
      hemolysis in 14 days. In conclusion, a large volume of RBCs can be treated with
      DTT and stored in Alsever's solution for use without deterioration of the RBC
      antigens, saving institutions tech time, resources, and money.

PMID- 29043828
TI  - A LU:-16 individual with antibodies.
AB  - CONCLUSIONS: Antibodies against Lutheran blood group antigens have been observed
      during first-time pregnancy. Samples from a woman of African descent were tested
      in our immunohematology laboratory on several occasions since 2001. Her samples
      were phenotyped as Lu(a+b-), and anti-Lub was suspected but not identified. She
      was asked to make autologous donations in preparation for her delivery, which she
      did. In 2010, two antibodies were identified: anti-Lea and -Lub. Six years later,
      a third investigation was requested. This time, an antibody directed at a high
      prevalence Lutheran antigen was found in addition to the anti-Lea and -Lub
      previously observed. Her serum was compatible with three out of five Lu(a-b-)
      reagent red blood cells (RBCs). One of the incompatible Lu(a-b-) reagent RBCs was
      known to be In(Lu) (KLF1 mutation). The genetic background of the other reagent
      RBC was unknown. The LU cDNA sequence analysis revealed the presence of the
      c.230G>A (Lua), c.679C>T (LU:-16), and a silent polymorphism c.1227G>T. Anti-Lu16
      was highly suspected. This would be the fifth case of LU:-16 with antibodies
      reported, all within women of African heritage with the Lu(a+b-) phenotype.
      Hemolytic disease of the fetus and newborn was not noted in these cases.

PMID- 29043829
TI  - Postpartum acute hemolytic transfusion reactions associated with anti-Lea in two
      pregnancies complicated by preeclampsia.
AB  - CONCLUSIONS: Lewis blood group antibodies, which are mostly naturally occurring
      and considered clinically insignificant, have rarely been documented as a cause
      of acute hemolytic transfusion reactions (AHTRs). This report presents two cases
      of AHTRs caused by anti-Lea occurring in postpartum black females (one group B,
      one group AB) whose pregnancies were complicated by preeclampsia. Neither anti
      Lea was detected by automated solid-phase red cell adherence technology in pre
      transfusion testing. Therefore, red blood cell units, compatible by electronic
      crossmatch, were issued and transfused. The subsequent transfusion reactions were
      characterized by acute intravascular hemolysis, evidenced by both clinical and
      laboratory criteria. These two cases demonstrate that, even when least
      anticipated, hemolytic transfusion reactions may occur. As expected, neither live
      born neonate was affected by hemolytic disease of the fetus and newborn. Because
      both transfusion reactions occurred in non-group O, postpartum black females with
      pregnancies complicated by preeclampsia, possible links between in vivo hemolytic
      anti-Lea, non-group O pregnant black females, and preeclampsia may require
      additional investigation.

PMID- 29043830
TI  - Red blood cell phenotype prevalence in blood donors who self-identify as
      Hispanic.
AB  - CONCLUSIONS: Molecular genotyping platforms provide a quick, high-throughput
      method for identifying red blood cell units for patients on extended phenotype
      matching protocols, such as those with sickle cell disease or thalassemia. Most
      of the antigen prevalence data reported are for non-Hispanic populations.
      Therefore, this study sought to determine the phenotype prevalence in a single
      blood center's Hispanic population and to compare those results with previously
      reported rates in non-Hispanic donor populations. We performed a retrospective
      review of all serologic and molecular typing from donors who self-reported as
      Hispanic. The phenotype prevalence was reported and compared with rates from
      other racial/ethnic groups. A total of 1127 donors who selfidentified as Hispanic
      were screened by serologic methods for Rh and Kell antigens, and 326 were
      subsequently selected for molecular typing. The most prevalent probable Rh
      phenotypes were R1r (26.6%), R1R2 (21.5%), and R1R1 (20.7%); rr was found in 7.8
      percent of donors tested. The percentage of K+ donors in this population was 2.8
      percent. The most prevalent Duffy phenotypes were Fy(a+b+) (35.9%), Fy(a+b-)
      (35.6%), and Fy(a-b+) (27%). Of the donors studied, 15.3 percent had an FY GATA
      mutation. Only 1.5 percent of the donors were Fy(a-b-). The Jk(a+b+) phenotype
      was found in nearly half of the population. M+N+S+s+ was the most prevalent MNS
      phenotype from that group, constituting 22.4 percent. A total of 95.7 percent of
      the donors were Lu(a-b+), and Di(a-b+) was observed in 94.4 percent. The most
      prevalent Dombrock phenotype was Do(a+b+), constituting 46.9 percent, followed
      closely by Do(a-b+) at 40.5 percent. Hispanic donor antigen prevalence is
      distinctly different from other racial/ethnic groups and should be considered
      when attempting to find extended matched units for these patients.

PMID- 29043831
TI  - DEL phenotype.
AB  - CONCLUSIONS: DEL red blood cells (RBCs) type as D- by routine serologic methods
      and are transfused routinely, without being identified as expressing a very weak
      D antigen, to D- recipients. DEL RBCs are detected only by adsorption and elution
      of anti-D or by molecular methods. Most DEL phenotypes have been reported in
      population studies conducted in East Asia, although DEL phenotypes have been
      detected also among Caucasian individuals. Approximately 98 percent of DEL
      phenotypes in East Asians are associated with the RHD*DEL1 or RHD*01EL.01 allele.
      The prevalence of DEL phenotypes has been reported among D- Han Chinese (30%),
      Japanese (28%), and Korean (17%) populations. The prevalence of DEL phenotypes is
      significantly lower among D- Caucasian populations (0.1%). Among the 3-5 percent
      of African individuals who are D-, there are no reports of the DEL phenotype.
      Case reports from East Asia indicate that transfusion of DEL RBCs to D-
      recipients has been associated with D alloimmunization. East Asian immigrants
      constitute 2.1 percent of the 318.9 million persons residing in the United
      States, and an estimated 2.8 percent are blood donors. Using these statistics, we
      estimate that 68-683 units of DEL RBCs from donors of East Asian ancestry are
      transfused as D- annually in the United States. Given the reports from East Asia
      of D alloimmunization attributed to transfusion of DEL RBCs, one would expect an
      occasional report of D alloimmunization in the United States following
      transfusion of DEL RBCs to a D- recipient. If such cases do occur, the most
      likely reason that they are not detected is the absence of active post
      transfusion monitoring for formation of anti-D.

PMID- 29043832
TI  - High-Frequency Oscillation for Adult Patients with Acute Respiratory Distress
      Syndrome. A Systematic Review and Meta-Analysis.
AB  - RATIONALE: By minimizing tidal lung strain and maintaining alveolar recruitment,
      high-frequency oscillatory ventilation (HFOV) may protect against ventilator
      induced lung injury. OBJECTIVES: To summarize the current evidence in support of
      the use of HFOV in adult patients with acute respiratory distress syndrome.
      METHODS: We conducted a systematic review and meta-analysis of randomized trials
      comparing mortality rates with the use of HFOV versus conventional mechanical
      ventilation for adult patients with acute respiratory distress syndrome. Eligible
      trials were identified from previously published systematic reviews and an
      updated literature search. Data on 28-day mortality, oxygenation, adverse events,
      and use of rescue therapies were collected; effects were pooled using random
      effects models weighted by inverse variance. Strength of evidence was assessed
      using Grading of Recommendations Assessment, Development, and Evaluation
      methodology. RESULTS: Six trials were eligible for inclusion (total n = 1,715
      patients). Four trials mandated lung-protective ventilation in the control group
      and one trial applied a higher positive end-expiratory pressure (PEEP)
      ventilation strategy in the control group. None of the trials were judged to be
      at high risk of bias, though all were unblinded. In trials that did not
      systematically employ any cointerventions with HFOV and that targeted low tidal
      volumes in the patients randomized to conventional ventilation (primary
      analysis), HFOV had no significant effect on mortality (three trials; risk ratio
      [RR], 1.14; 95% confidence interval [CI], 0.88 to 1.48; evidence grade = high).
      Pooled analysis of all six trials also did not suggest a significant mortality
      reduction (RR, 0.94; 95% CI, 0.71 to 1.24; evidence grade = low). The single
      trial that employed a conventional ventilation strategy with both lower tidal
      volumes and higher PEEP as control reported higher mortality in patients
      receiving HFOV (RR, 1.41; 95% CI, 1.12 to 1.79). HFOV was not associated with
      improved oxygenation after 24 hours (five trials; mean increase of 10 mm Hg; 95%
      CI, -16 to 37 mm Hg). Rates of barotrauma were not different between HFOV and
      conventional ventilation, although significant benefit or harm could not be
      excluded (RR, 1.15; 95% CI, 0.61 to 2.17). CONCLUSIONS: Published randomized
      trials suggest that HFOV is not associated with a mortality benefit, and may even
      be harmful in comparison to ventilation with low tidal volumes and higher levels
      of PEEP.

PMID- 29043833
TI  - The Fetus or the Infant: Which Is the Father of the Man? (Both).

PMID- 29043834
TI  - Higher PEEP versus Lower PEEP Strategies for Patients with Acute Respiratory
      Distress Syndrome. A Systematic Review and Meta-Analysis.
AB  - RATIONALE: Higher positive end-expiratory pressure (PEEP) levels may reduce
      atelectrauma, but increase over-distention lung injury. Whether higher PEEP
      improves clinical outcomes among patients with acute respiratory distress
      syndrome (ARDS) is unclear. OBJECTIVES: To compare clinical outcomes of
      mechanical ventilation strategies using higher PEEP levels versus lower PEEP
      strategies in patients with ARDS. METHODS: We performed a systematic review and
      meta-analysis of clinical trials investigating mechanical ventilation strategies
      using higher versus lower PEEP levels. We used random effects models to evaluate
      the effect of higher PEEP on 28-day mortality, organ failure, ventilator-free
      days, barotrauma, oxygenation, and ventilation. RESULTS: We identified eight
      randomized trials comparing higher versus lower PEEP strategies, enrolling 2,728
      patients with ARDS. Patients were 55 (+/-16) (mean +/- SD) years old and 61% were
      men. Mean PEEP in the higher PEEP groups was 15.1 (+/-3.6) cm H2O as compared
      with 9.1 (+/-2.7) cm H2O in the lower PEEP groups. Primary analysis excluding two
      trials that did not use lower Vt ventilation in the lower PEEP control groups did
      not demonstrate significantly reduced mortality for patients receiving higher
      PEEP as compared with a lower PEEP (six trials; 2,580 patients; relative risk,
      0.91; 95% confidence interval [CI] = 0.80-1.03). A higher PEEP strategy also did
      not significantly decrease barotrauma, new organ failure, or ventilator-free days
      when compared with a lower PEEP strategy (moderate-level evidence). Quality of
      evidence for primary analyses was downgraded for precision, as CIs of outcomes
      included estimates that would result in divergent recommendations for use of
      higher PEEP. Secondary analysis, including trials that did not use low Vt in low
      PEEP control groups, showed significant mortality reduction for high-PEEP
      strategies (eight trials; 2,728 patients; relative risk, 0.84; 95% CI = 0.71
      0.99), with greater mortality benefit observed for high PEEP in trials that did
      not use lower Vts in the low-PEEP control group (P = 0.02). Analyses stratifying
      by use of recruitment maneuvers (P for interaction = 0.69), or use of
      physiological targets to set PEEP versus PEEP/FiO2 tables (P for interaction =
      0.13), did not show significant effect modification. CONCLUSIONS: Use of higher
      PEEP is unlikely to improve clinical outcomes among unselected patients with
      ARDS.

PMID- 29043835
TI  - We Have to Learn to Do without Knowing Enough: Antieosinophilic Treatments for
      Severe Asthma.

PMID- 29043836
TI  - Amphetamine Derivatives and the Risk of Pulmonary Arterial Hypertension. A New
      Chapter of the Story.

PMID- 29043837
TI  - Lung Recruitment Maneuvers for Adult Patients with Acute Respiratory Distress
      Syndrome. A Systematic Review and Meta-Analysis.
AB  - RATIONALE: In patients with acute respiratory distress syndrome (ARDS), lung
      recruitment maneuvers (LRMs) may prevent ventilator-induced lung injury and
      improve survival. OBJECTIVES: To summarize the current evidence in support of the
      use of LRMs in adult patients with ARDS and to inform the recently published
      American Thoracic Society/European Society of Intensive Care Medicine/Society of
      Critical Care Medicine clinical practice guideline on mechanical ventilation in
      ARDS. METHODS: We conducted a systematic review and meta-analysis of randomized
      trials comparing mechanical ventilation strategies with and without LRMs.
      Eligible trials were identified from among previously published systematic
      reviews and an updated literature search. Data on 28-day mortality, oxygenation,
      adverse events, and use of rescue therapy were collected, and results were pooled
      using random effects models weighted by inverse variance. Strength of evidence
      was assessed using the Grading of Recommendations Assessment, Development, and
      Evaluation methodology. RESULTS: We screened 430 citations and previous
      systematic reviews and found six trials eligible for inclusion (n = 1,423
      patients in total). The type of LRM varied widely between trials, and five of the
      trials involved a cointervention with a higher positive end-expiratory pressure
      (PEEP) ventilation strategy. Risk of bias was deemed high in one trial. In the
      primary analysis, the only trial without a cointervention showed that LRMs were
      associated with reduced mortality (one trial; risk ratio [RR], 0.62; 95%
      confidence interval [CI], 0.39-0.98; evidence grade = low). Meta-analysis of all
      six trials also suggested a significant mortality reduction (six trials; RR,
      0.81; 95% CI, 0.69-0.95; evidence grade = moderate), and the use of a higher PEEP
      cointervention did not significantly modify the mortality effect (P = 0.27 for
      heterogeneity). LRMs were also associated with improved oxygenation after 24
      hours (six trials; mean increase, 52 mm Hg; 95% CI, 23-81 mm Hg) and less
      frequent requirement for rescue therapy (three trials; RR, 0.65; 95% CI, 0.45
      0.94). LRMs were not associated with an increased rate of barotrauma (four
      trials; RR, 0.84; 95% CI, 0.46-1.55). The rate of hemodynamic compromise was not
      significantly increased with LRMs (three trials; RR, 1.30; 95% CI, 0.92-1.78).
      CONCLUSIONS: Randomized trials suggest that LRMs in combination with a higher
      PEEP ventilation strategy reduce mortality, but confidence in this finding is
      limited. Further trials are required to confirm benefit from LRMs in adults with
      ARDS.

PMID- 29043838
TI  - Blink: Characteristics, Controls, and Relation to Dry Eyes.
AB  - Blink is a complex phenomenon that is profoundly affected by diverse endogenous
      and exogenous stimuli. It has been studied in the context of cognition,
      emotional, and psychological states, as an indicator of fatigue and sleepiness,
      particularly in the automobile and transportation industry, in visual tasking,
      and finally, as it relates to tear film stability and ocular surface health. The
      fact that it is highly variable and has input from so many sources makes it very
      difficult to study. In the present review, the behavior of blink in many of these
      systems is discussed, ultimately returning in each instance to a discussion of
      how these factors affect blink in the context of dry eyes. Blink is important to
      ocular surface health and to an individual's optimal functioning and quality of
      life. Disturbances in blink, as cause or effect, result in a breakdown of tear
      film stability, optical clarity, and visual function.

PMID- 29043839
TI  - Less Is More for Steroids in Severe Sepsis and Oxygen for the Critically Ill, but
      Maybe Not When Searching for Pulmonary Embolism in Syncope.

PMID- 29043840
TI  - Comparison of two methods based on photoplethysmography for the diagnosis of
      peripheral arterial disease.
AB  - AIM: To examine the interchangeability of two methods for distal pressure
      measurement based on photoplethysmography using a truncated or full display of
      the arterial inflow curve, respectively. METHODS: Toe and ankle pressures were
      obtained from 69 patients suspected of peripheral arterial disease (PAD).
      Observer reproducibility of the curve readings was examined by blinded
      reassessment of the pressure curves in a randomly selected subgroup (60 limbs).
      RESULTS: There were no significant differences in mean pressures between the two
      methods (p for all > .455). The limits of agreement for the differences were 
      15.0-15.4 mmHg for right toe pressures, -16.3-16.2 mmHg for left toe pressures, 
      14.2-15.7 mmHg for right ankle pressures, and -18.3-17.7 mmHg for left ankle
      pressures. Correlation analysis revealed intraclass correlation coefficients
      >=0.960 for all measuring sites. Cohen's Kappa showed excellent agreement in
      diagnostic classification, with kappa = 0.930 for the diagnosis of PAD and
      perfect agreement in the diagnosis of critical limb ischemia (kappa = 1.000). The
      analysis of intra-observer variation for curve reading showed limits of agreement
      of -3.9-4.0 for toe pressures and -7.6-7.7 for ankle pressures for the method
      involving truncated display and -3.1-3.2 for toe pressures and -6.3-8.6 for ankle
      pressures for the method involving full display of the signal. CONCLUSION: The
      present study shows minimal differences in diagnostic classification, as well as
      in ankle and toe pressures, between the full display and the truncated display of
      the photoplethysmographic pulse signal. Furthermore, the inter-observer variation
      was low for both of the photoplethysmographic methods investigated.

PMID- 29043841
TI  - Tactics Young Women Use to Resist Condom Use When a Partner Wants to Use a
      Condom.
AB  - Although there is a growing literature on men's condom use resistance (CUR)
      tactics (e.g., direct requests, deception), little research exists on women's CUR
      tactics. This study investigated young women's (ages 18 to 21) self-reported use
      of CUR tactics since age 14 and related individual difference factors.
      Participants included 235 sexually active heterosexual women from a nationwide
      convenience survey sample who completed a newly adapted women's version of the
      Condom Use Resistance Survey. Consistent with the limited previous research,
      women were most likely to use risk-level reassurance (37.9%) and seduction
      (33.2%) tactics. A higher frequency and quantity of alcohol consumption,
      particularly prior to sex, lower perceived risk of sexually transmitted
      infections (STIs), and a history of STI diagnosis were associated with having
      previously used a greater number and variety of CUR tactics. This highlights the
      need for CUR prevention and intervention programming for women. Future research
      should specifically examine women's rationale for using CUR tactics and utilize
      longitudinal and experimental methods to further elucidate directional and causal
      relationships among individual-level risk factors, CUR, and negative sexual
      health outcomes.

PMID- 29043842
TI  - The Protective and Immunomodulatory Effects of Fucoidan Against 7,12-Dimethyl
      benz[a]anthracene-Induced Experimental Mammary Carcinogenesis Through the
      PD1/PDL1 Signaling Pathway in Rats.
AB  - Fucoidan is a sulfated polysaccharide that is extracted from brown algae seaweed.
      This study was designed to evaluate the protective and immunomodulatory effects
      of dietary fucoidan on 7,12-dimethyl benz[a]anthracene (DMBA)-induced
      experimental mammary carcinogenesis in rats. Sixty Sprague-Dawley rats were
      randomly assigned to four equal groups: the control group (control group), the
      cancer model group (model group), and the F1 and F2 groups, which were fed
      fucoidan at concentrations of 200 and 400 mg/kg.body weight, respectively. We
      found that fucoidan treatment decreased the tumor incidence and mean tumor weight
      and prolonged the tumor latency. Flow cytometric analyses revealed that the
      number of blood natural killer cells was higher after fucoidan treatment and that
      the proportions of CD4 and CD8 T cells were also increased. The serum levels of
      interleukin (IL)-6, IL-12p40, and interferon (IFN)-gamma were higher in the rats
      treated with fucoidan compared to those of model rats. Moreover, the percentage
      of CD3+ Foxp3+ regulatory T cells in the blood and the levels of IL-10 and
      transforming growth factor beta in the serum were lower in the rats treated with
      fucoidan. Furthermore, fucoidan treatment decreased the expression of Foxp3 and
      programmed cell death 1 ligand 1 (PDL1) in tumor tissues. The levels of p
      phosphatidyl inositol kinase 3 and p-AKT in tumor tissues were also lower than
      those of model rats. These results suggest that a fucoidan-supplemented diet can
      inhibit DMBA-induced tumors in rats. This study provides experimental evidence
      toward elucidating the immune enhancement induced by fucoidan through the
      programmed cell death 1/PDL1 signaling pathway. The immunomodulatory effect is
      one of the possible mechanisms of the protective effect of fucoidan against
      mammary carcinogenesis.

PMID- 29043843
TI  - Parenting a Child With Complex Health Care Needs: A Stressful and Imposed
      "Clinical Career".

PMID- 29043846
TI  - "Gay Equals White"? Racial, Ethnic, and Sexual Identities and Attitudes Toward
      LGBT Individuals Among College Students at a Bible Belt University.
AB  - While past research has certainly explored a variety of correlates of attitudes
      toward lesbian, gay, bisexual, and transgender (LGBT) individuals, the current
      study is among the first in an emerging line of inquiry that examines attitudes
      toward each of these groups separately utilizing an intersectional framework with
      special attention to racial, ethnic, and sexual identities. Using a college
      sample of students from the Bible Belt of the United States (N = 1,940), I
      investigated the roles of racial and ethnic identities (Caucasian/White, African
      American/Black, Asian/Pacific Islander, Native American/Alaskan Native, other
      race, and Hispanic/Latinx), religiosity, patriarchal gender norms, parental
      perspectives, and the intersections among these identities and experiences as
      they relate to attitudes toward LGBT individuals among heterosexual (n = 1,551)
      and LGB respondents (n = 389). This moves beyond explorations of White
      heterosexual people's attitudes about "homosexuals" (i.e., away from a focus only
      on gayness and Whiteness) and expands to include non-White LGB people's LGBT
      attitudes. Overall, results indicate that racial, ethnic, and sexual identities
      play a significant role in southern college students' LGBT attitudes, and these
      patterns are further complicated by interacting cultural experiences with
      religiosity, patriarchy, and family dynamics. Campus policy and program
      implications are provided.

PMID- 29043849
TI  - Absorption of ibuprofen orodispersible tablets in early postoperative phase - a
      pharmacokinetic study.
AB  - OBJECTIVE: Patient-controlled oral analgesia has gained popularity in
      postoperative pain management. Anesthesia and surgery delay gastrointestinal
      tract function and this may therefore decrease bioavailability of drugs taken by
      mouth. To hasten absorption, an orodispersible ibuprofen tablet has been
      developed. In this study, we evaluated the pharmacokinetics and feasibility of
      orodispersible ibuprofen tablets in spine surgery patients. METHODS: The study
      design was a prospective clinical trial where each patient served as her/his own
      control. Fifteen patients aged 19-75 years were given two orodispersible
      ibuprofen 200 mg tablets the day before surgery and two more tablets immediately
      after surgery. Blood samples for ibuprofen concentrations were taken at intervals
      for 6 hours following pre- and postsurgical administration of ibuprofen. RESULTS:
      The mean preoperative area under time-concentration curve for ibuprofen (AUC0
      360) was 4806 (SD 1104) min.mg/L, and after surgery it was 2141 (583) min.mg/L
      (mean difference 2664, 95% CI for difference 2003 to 3325, p < .001). The mean of
      the maximum preoperative plasma concentration of ibuprofen was three times
      higher, 26.7 (7.7) mg/L, than the postoperative value of 8.6 (2.1) mg/L (mean
      diff. 18.1, 95% CI 13.9 to 22.4, p < .001). Times to maximum concentration were
      similar pre- and postoperatively at 155 (58) minutes and 169 (113) minutes (p =
      .67). No serious or unexpected adverse events were recorded. CONCLUSIONS: While
      orodispersible ibuprofen tablets were feasible, ibuprofen absorption decreased
      immediately after surgery compared to the day before surgery. Thus, further
      studies are needed to establish the adequate initial postoperative dose.

PMID- 29043847
TI  - Smoking-Related Interstitial Fibrosis: Evidence of Radiologic Regression with
      Advancing Age and Smoking Cessation.
AB  - More data are needed regarding the radiology, co-morbidities and natural history
      of smoking-related interstitial fibrosis (SRIF), a common pathological finding,
      mainly described heretofore in association with lung cancer, where respiratory
      bronchiolitis (RB) usually co-exists. We prospectively acquired high resolution
      CT scan data (edge-enhancing lung reconstructions) to detect any radiologic
      interstitial lung abnormality (ILA) in individuals who ultimately underwent
      surgical lobectomy for lung cancer (n = 20), for radiologic/pathologic
      correlation. We also re-examined other smoking-related benign histologic cases:
      chronic obstructive pulmonary disease (COPD lung explants, n = 20), alpha 1
      antitrypsin deficiency (A1AT, explanted lungs n = 20), combined pulmonary
      fibrosis and emphysema (CPFE, n = 8) and idiopathic pulmonary fibrosis (IPF, n =
      10). Finally, we pooled our data with all peer-reviewed published data describing
      histologic SRIF of known ILA status. SRIF was observed in 40% of cancer
      lobectomies, mean (+/-SD) age 65.8 +/- 8.7 years, none of whom had ILA. SRIF was
      observed in other smoking-related benign diseases (COPD 35%, A1AT 20%, CPFE 25%,
      and IPF 10%). 71.4% of benign SRIF cases had no RB (nearly all ex-smokers) versus
      0% of cancer-associated SRIF cases (P = 1.7 * 10-3). Pooled data showed that
      those SRIF subjects without ILA were 15.05 years older than those with ILA (95%
      confidence interval 8.99 to 21.11, P = 2.5 * 10-5) and more likely to be former
      smokers (P = 7.2 * 10-3). SRIF is frequently found without lung cancer, and
      mostly without RB in former smokers. SRIF is less likely to have ILA in older
      subjects and with smoking cessation, which could represent RB+/-SRIF regression.

PMID- 29043848
TI  - Lexical access in a bilingual speaker with dementia: Changes over time.
AB  - In this article, we explore the naming skills of a bilingual English-Norwegian
      speaker diagnosed with Primary Progressive Aphasia, in each of his languages
      across three different speech contexts: confrontation naming, semi-spontaneous
      narrative (picture description), and conversation, and at two points in time: 12
      and 30 months post diagnosis, respectively. The results are discussed in light of
      two main theories of lexical retrieval in healthy, elderly speakers: the
      Transmission Deficit Hypothesis and the Inhibitory Deficit Theory. Our data show
      that, consistent with the participant's premorbid use of and proficiency in the
      two languages, his performance in his L2 is lower than in his L1, but this
      difference diminishes as the disease progresses. This is the case across the
      three speech contexts; however, the difference is smaller in the narrative task,
      where his performance is very low in both languages already at the first
      measurement point. Despite his word finding problems, he is able to take active
      part in conversation, particularly in his L1 and more so at the first measurement
      point. In addition to the task effect, we find effects of word class, frequency,
      and cognateness on his naming skills. His performance seems to support the
      Transmission Deficit Hypothesis. By combining different tools and methods of
      analysis, we get a more comprehensive picture of the impact of the dementia on
      the speaker's languages from an intra-individual as well as an inter-individual
      perspective, which may be useful in research as well as in clinical practice.

PMID- 29043850
TI  - Age-adjusted D-dimer cut-off in the diagnostic strategy for deep vein thrombosis:
      a systematic review.
AB  - BACKGROUND: Studies have indicated that use of an age-adjusted D-dimer cut-off
      value for patients above 50 years increases utility of the diagnostic strategy
      for pulmonary embolism. Evidence for the same approach regarding diagnosis of
      deep vein thrombosis (DVT) is, however, unclear. MATERIALS AND METHODS: A
      systematic literature review was conducted following the PRISMA Statement
      guideline to gather the existing knowledge on the use of an age-adjusted D-dimer
      cut-off in the diagnostic strategy for DVT. Studies were extracted from Medline
      and the Cochrane Library. The search period ended in November 2016. RESULTS: Out
      of 73 articles retrieved, only eight studies addressed DVT either specifically or
      along with PE. None of these were randomized controlled trials, but were either
      prospective studies of consecutive outpatients or retrospective studies. Despite
      differences in study design, DVT prevalence, and D-dimer assay used, all studies
      were in favour of the age-adjusted D-dimer cut-off with negative predictive
      values (NPV) ranging from 91.8-100% compared to 89.7-100% for the standard D
      dimer cut-off. All the studies concluded that use of an age-adjusted D-dimer cut
      off resulted in an improved utility, although the results due to heterogeneity in
      reporting did not allow a direct comparison. CONCLUSION: Use of an age-adjusted D
      dimer cut-off for patients above 50 years of age for ruling out DVT seems as safe
      as using a standard D-dimer cut-off. The recommended (and most used) adjustment
      is by the formula (patient's age *10) MUg/L.

PMID- 29043851
TI  - Antioxidants in the Treatment of Cancer.
AB  - Several clinical trials have produced conflicting results regarding the benefit
      of antioxidants in cancer therapy thus questioning the incorporation of these
      substances in standard treatment regimens. Vitamins E and C, selenium,
      carotenoids, lycopene, soy products, and green tea extract are a few substances
      with antioxidant properties that have been studied in detail. This article
      reviews the results generated over the last 20 years through in vitro and in vivo
      studies in various types of cancers and stages of cancer treatment. Despite the
      commercial popularity and the multitude of studies examining antioxidant therapy,
      the true role of antioxidants is yet to be determined, requiring further
      investigation into its propagative, causal, or protective nature.

PMID- 29043852
TI  - Beliefs About Others' Perceptions-Gender Typicality: Scale Development and
      Relationships to Gender Nonconformity, Sexual Orientation, and Well-Being.
AB  - The purpose of this study was to develop a measure of "other-perceived" gender
      typicality and test its relationship with gender nonconformity, sexual
      orientation, and psychological distress. Data on these variables were collected
      from 632 participants (142 heterosexual men, 77 gay men, 50 bisexual men, 174
      heterosexual women, 85 lesbian women, and 104 bisexual women). We designed a
      Beliefs About Others' Perceptions-Gender Typicality (BOP-GT) scale on which
      participants reported how masculine or feminine they thought other people
      perceived their gendered behavior, interests, appearance, and activities. Factor
      analysis identified five factors: appearance, emotional response, sporting
      interests, occupational interests, and interpersonal style. Recalled childhood
      gender nonconformity (CGN) was significantly associated with each BOP-GT
      subscale. Heterosexual men rated that other people perceived them to be more
      masculine scoring on the BOP-GT compared to heterosexual women. Gay men and
      lesbian women showed cross-sexed patterns on the BOP-GT total scale, appearance,
      emotional response, and sporting interests scores. Bisexual men and women were
      generally no different from the other male and female groups, respectively.
      Bisexual women had greater distress scores, and the BOP-GT emotional response
      subscale was associated with somewhat greater distress scores. The BOP-GT measure
      may have use in future research on understanding gendered self-concepts.

PMID- 29043853
TI  - Microvascular Network and Its Endothelial Cells in the Human Iris.
AB  - PURPOSE: The iris allows effective delivery of nutrients into the aqueous humor
      supplying the surrounded avascular tissues. However, possible underlying
      mechanisms of the iris vasculature have not been well established. This study
      aims to quantitatively assess the human iris vascular network, endothelial cell
      morphometries, and characterize endothelial junctions to better understand the
      properties of the iris vasculature. MATERIALS AND METHODS: The irises from human
      donor eyes were dissected and short fixed before float staining for VE-cadherin
      and claudin-5, f-actin and nuclei and flat-mounted for confocal imaging. The iris
      microvasculature was studied for its distribution and branch orders. The
      endothelial and nuclear morphometrics were measured for each vessel order.
      Characteristics of cellular junction staining and intracellular cytoskeleton were
      investigated. RESULTS: The human iris vasculature was found to comprise of six
      orders of arteries, three orders of veins, and capillaries. The endothelial cell
      shape was long and narrow in all arteries, suggesting a high hemodynamic shear
      stress. Relatively large vessels ran radially in the superficial two-thirds of
      the iris, while smaller and denser vessels ran in the deepest third. Significant
      heterogeneity in vascular diameter, shape of the endothelia and nuclei, and the
      nuclear position was evident between artery, capillary and vein. Staining of
      junction proteins VE-cadherin and claudin-5 appeared non-uniform at the cell
      borders, especially in large veins. CONCLUSIONS: High rates of blood flow and
      special barrier properties are indicated by the morphological properties of the
      human iris vasculature. Detailed information of the iris vasculature combined
      with the inter- and intra-endothelial structure may help us further understand
      the physiological and pathogenic roles of the iris.

PMID- 29043854
TI  - The epigenetic landscape of myalgic encephalomyelitis/chronic fatigue syndrome:
      deciphering complex phenotypes.

PMID- 29043855
TI  - Predictors of receptive and expressive vocabulary development in children with
      Down syndrome.
AB  - PURPOSE: There is a lack of longitudinal data on predictors of vocabulary
      development in children with Down syndrome (DS). In typically developing
      children, many internal and external predictors of vocabulary development have
      been determined before. The purpose of the present study was to investigate the
      role of these variables in the receptive and expressive vocabulary development of
      children with DS. METHOD: The present study used a longitudinal design in young
      children with DS to study the vocabulary development over a period of 1.6 years
      and investigated the possible predictive role of child-related and environmental
      variables. RESULT: Receptive vocabulary development was best predicted by the
      adaptive level of functioning and early receptive vocabulary skills. Expressive
      vocabulary development was best predicted by the adaptive level of functioning,
      receptive vocabulary, maternal educational level, level of communicative intent
      of the child, attention skills and phonological/phonemic awareness. CONCLUSION: A
      wide range of internal and external predictors for vocabulary development of
      children with DS was found. Predictors resemble those predicting vocabulary
      development in peers with typical development between 1 and 6 years of age, as
      identified in other studies.

PMID- 29043856
TI  - Genome-Wide Association Study of 58 Individuals with Fibrosing Mediastinitis
      Reveals Possible Underlying Genetic Susceptibility.

PMID- 29043857
TI  - Magnetic carbon nanotubes: preparation, physical properties, and applications in
      biomedicine.
AB  - Magnetic carbon nanotubes (MCNTs) have been widely studied for their potential
      applications in medicine, diagnosis, cell biology, analytical chemistry, and
      environmental technology. Introduction of MCNTs paved the way for the emergence
      of new approaches in nanobiotechnology and biomedicine as a result of their
      multifarious properties embedded within either the carbon nanotubes (CNTs) or
      magnetic parts. Numerous preparation techniques exists for functionalizing CNTs
      with magnetic nanoparticles, and these versatile strategies lay the ground for
      the generation of novel and versatile systems which are applicable to many
      industries and biological areas. Here, we review and discuss the recent papers
      dealing with MCNTs and their application in biomedical and industrial fields.

PMID- 29043858
TI  - Melanoma segmentation based on deep learning.
AB  - Malignant melanoma is one of the most deadly forms of skin cancer, which is one
      of the world's fastest-growing cancers. Early diagnosis and treatment is
      critical. In this study, a neural network structure is utilized to construct a
      broad and accurate basis for the diagnosis of skin cancer, thereby reducing
      screening errors. The technique is able to improve the efficacy for
      identification of normally indistinguishable lesions (such as pigment spots)
      versus clinically unknown lesions, and to ultimately improve the diagnostic
      accuracy. In the field of medical imaging, in general, using neural networks for
      image segmentation is relatively rare. The existing traditional machine-learning
      neural network algorithms still cannot completely solve the problem of
      information loss, nor detect the precise division of the boundary area. We use an
      improved neural network framework, described herein, to achieve efficacious
      feature learning, and satisfactory segmentation of melanoma images. The
      architecture of the network includes multiple convolution layers, dropout layers,
      softmax layers, multiple filters, and activation functions. The number of data
      sets can be increased via rotation of the training set. A non-linear activation
      function (such as ReLU and ELU) is employed to alleviate the problem of gradient
      disappearance, and RMSprop/Adam are incorporated to optimize the loss algorithm.
      A batch normalization layer is added between the convolution layer and the
      activation layer to solve the problem of gradient disappearance and explosion.
      Experiments, described herein, show that our improved neural network architecture
      achieves higher accuracy for segmentation of melanoma images as compared with
      existing processes.

PMID- 29043859
TI  - Gastrointestinal bleeding associated with chronic excessive use overdosing with
      topical ketoprofen patch in elderly patient.
AB  - PURPOSE: Topical ketoprofen patch has been developed to reduce the risk of
      systemic adverse effects such as gastrointestinal injury and renal toxicity.
      MATERIALS AND METHODS: We reported here a case of lower intestinal bleeding
      associated with chronic excessive use of topical ketoprofen patch in an elderly
      patient. RESULTS: A 74-year-old female visited to the outpatient clinic of the
      Gifu University Hospital and admitted thereafter. She had fecal occult blood and
      anemia. Enteroscopic examination showed several ulcerative lesions and a
      protruded lesion accompanied with redness in the small intestinal mucosa. She
      used 8 sheets of 20 mg ketoprofen patch every day for a long period to relieve
      pain in the shoulder, lower back and lower limb. She had no diseases that are
      related to the initiation of gastrointestinal bleeding, including infection,
      inflammatory bowel disease, autoimmune disease and malignant disease. Thus, the
      present lower intestinal bleeding was concluded to be due to the use of topical
      ketoprofen patch. The symptoms were recovered after cessation of the patch.
      CONCLUSIONS: Extensive care should be taken to avoid ulcerative intestinal
      hemorrhage to elderly patients receiving multiple doses of non-steroidal anti
      inflammatory drug patch for multiple days.

PMID- 29043860
TI  - Development and in vitro/in vivo evaluation of HPMC/chitosan gel containing
      simvastatin loaded self-assembled nanomicelles as a potent wound healing agent.
AB  - The aim of this study was to develop hydroxypropyl methyl cellulose
      (HPMC)/chitosan gel containing polymeric micelles loaded with simvastatin (Sim)
      and evaluates its wound healing properties in rats. An irregular full factorial
      design was employed to evaluate the effects of various formulation variables
      including polymer/drug ratio, hydration temperature, hydration time, and organic
      solvent type on the physicochemical characteristics of pluronic F127-cholesterol
      nanomicelles prepared using the film hydration method. Among single studied
      factors, solvent type had the most impact on the amount of drug loading and zeta
      potential. Particle size and release efficiency was more affected by hydration
      temperature. The optimized formulation suggested by desirability of 93.5% was
      prepared using 1 mg of Sim, 10 mg of copolymer, dichloromethane as the organic
      solvent, hydration time of 45 min and hydration temperature of 25  degrees C. The
      release of the drug from nanomicelles was found to be biphasic and showed a rapid
      release in the first stage followed by a sustained release for 96 h. The gel
      contained nanomicelles exhibited pseudo-plastic flow and more sustained drug
      release profile compared to nanomicelles. In excision wound model on normal rats,
      the wound closure of the group treated by Sim loaded micelles-gel was superior to
      other groups. Taken together, Sim loaded micelles-gel may represent a novel
      topical formulation for wound healing.

PMID- 29043861
TI  - Nasobiliary drainage can reduce the incidence of post-ERCP pancreatitis after
      papillary large balloon dilation plus endoscopic biliary sphincterotomy: a
      randomized controlled trial.
AB  - BACKGROUND AND AIMS: Post-endoscopic retrograde cholangiopancreatography (ERCP)
      pancreatitis can be reduced following endoscopic papillary balloon dilation with
      the placement of an endoscopic nasobiliary drainage (ENBD) catheter. The aim of
      this study was to determine whether the placement of an ENBD reduces the risk of
      post-ERCP pancreatitis following endoscopic papillary large balloon dilation
      together with endoscopic biliary sphincterotomy. METHODS: A total of 160 patients
      with bile duct stones were randomly assigned (1:1) to an ENBD group or no-ENBD
      group. The primary outcome of this study was the incidence of post-ERCP
      pancreatitis. The secondary outcome was the incidence of post-ERCP
      hyperamylasemia. RESULTS: In total, 160 patients were randomized, and 155 were
      found to be eligible for the analysis. The two groups were similar regarding
      clinical and demographic factors as well as patient- and procedure-related risk
      factors for post-ERCP pancreatitis. Post-ERCP pancreatitis developed in 9
      patients, that is, 8/77 (10.4%) of the control group and 1/78 (1.28%) of the ENBD
      group (p = .018; per protocol analysis). Intention to treat analysis also
      revealed that ENBD reduced the rate of post-ERCP pancreatitis (8/80 (10%) in the
      control group vs. 1/80 (1.25%) the ENBD group (p = .034)). Multivariate
      regression analysis identified not undergoing ENBD as an independent risk factor
      for post-ERCP pancreatitis (ENBD compared with no-ENBD: OR 0.087, 95% CI 0.011
      0.734; p = .025). CONCLUSION: This study demonstrated that placement of an ENBD
      was effective and safe for the prevention of post-ERCP pancreatitis in patients
      undergoing endoscopic papillary large balloon dilation together with endoscopic
      biliary sphincterotomy.

PMID- 29043862
TI  - The potential role of FDG PET-CT in the characterization of the activity of
      Crohn's disease, staging follow-up and prognosis estimation: a pilot study.
AB  - OBJECTIVES: FDG PET-CT is a global, noninvasive, sensitive method to determine
      the location and activity of inflammatory lesions. Segmental FDG uptake is
      proportional with immune cell infiltration of bowel. Our aim was to evaluate
      prospectively the role of PET in patients with active Crohn's disease (CD) before
      and after one year's biological therapy, and to compare simple endoscopic score
      for CD (SES-CD), CD activity index (CDAI) and global PET scores. We also analyzed
      the prognostic value of initial PET scores. PATIENTS: Twelve patients were
      selected: six male/six female, ages between 18 and 39, average: 24 years, with
      CDAI values >300. METHODS: We scored the FDG uptake in the small intestine and
      the four colon segments (on a scale 0-3 for each), and summed them thus forming a
      global PET score. The scoring was based on the maximal standardized uptake value
      of the intestinal segment, related to the SUVmax of the liver (as a reference for
      normal tissue activity). The SES-CD, CDAI and global PET scores before and after
      treatment were statistically compared. RESULTS: There were significant changes in
      CDAI and SES-CD after therapy, PET scores improved only in patients' subgroup
      with high (>4) initial PET score, indicating good prognosis of biological
      treatment. In active disease, PET was more informative than endoscopy to access
      the extent of the inflammation, and small intestine involvement. CONCLUSIONS: FDG
      PET-CT score is a promising, noninvasive complementary method in the staging,
      treatment planning and follow-up of CD. Limitation of the study is the small
      number of patients.

PMID- 29043863
TI  - Preparation and evaluation of Vinpocetine self-emulsifying pH gradient release
      pellets.
AB  - The main objective of this study was to develop a pH gradient release pellet with
      self-emulsifying drug delivery system (SEDDS), which could not only improve the
      oral bioavailability of Vinpocetine (VIN), a poor soluble drug, but reduce the
      fluctuation of plasma concentration. First, the liquid VIN SEDDS formulation was
      prepared. Then the self-emulsifying pH gradient release pellets were prepared by
      extrusion spheronization technique, and formulation consisted by the liquid
      SEDDS, absorbent (colloidal silicon dioxide), penetration enhancer (sodium
      chloride), microcrystalline cellulose, ethyl alcohol, and three coating materials
      (HPMC, Eudragit L30D55, Eudragit FS30D) were eventually selected. Three kinds of
      coated pellets were mixed in capsules with the mass ratio of 1:1:1. The release
      curves of capsules were investigated in vitro under the simulated
      gastrointestinal conditions. In addition, the oral bioavailability and
      pharmacokinetics of VIN self-emulsifying pH gradient release pellets, commercial
      tablets and liquid VIN SEDDS were evaluated in Beagle dogs. The oral
      bioavailability of self-emulsifying pH gradient release pellets was about 149.8%
      of commercial VIN tablets, and it was about 86% of liquid VIN SEDDS, but there
      were no significant difference between liquid SEDDS and self-emulsifying pH
      gradient release pellets. In conclusion, the self-emulsifying pH gradient release
      pellets could significantly enhance the absorption of VIN and effectively achieve
      a pH gradient release. And the self-emulsifying pH gradient release pellet was a
      promising method to improve bioavailability of insoluble drugs.

PMID- 29043864
TI  - Which analgesic is efficient prior to intrauterine device insertion?

PMID- 29043865
TI  - A pediatric case of acute megakaryocytic leukemia with double chimeric
      transcripts of CBFA2T3-GLIS2 and DHH-RHEBL1.

PMID- 29043866
TI  - Three-dimensional finite element analysis of glass fiber and cast metal posts
      with different alloys for reconstruction of teeth without ferrule.
AB  - The aim of this study was to evaluate different materials for restoration of
      teeth without ferrule by three-dimensional (3D) finite element analysis (FEA).
      Five models simulating the maxillary central incisor and surrounding bone were
      simulated according to the type of post: glass fibre post (GFP) or cast metal
      post (CMP) with different alloys such as gold (Au), silver-palladium (AgPd),
      copper-aluminum (CuAl) and nickel-chromium (NiCr). Models were designed using
      Invesalius and Rhinoceros. FEAs were made using FEMAP and NeiNastran, with an
      applied axial force of 100 N and oblique occlusal load at 45 degrees . Stress
      distribution among groups was analysed by two-way analysis of variance (ANOVA),
      followed by post-hoc Tukey's test. The GFP showed the best stress distribution in
      the post, followed by CMP with Au, AgPd, CuAl and NiCr alloys, respectively (p <
      .001). No statistically significant difference in the stress distribution in
      teeth was found under application of axial load (p > .05). Under oblique load,
      the GFP generated the highest values of tension among the models, followed by the
      CMP with NiCr alloy than other models (p < .001). The use of GFP resulted in a
      lower stress concentration in the post, but increased stress in the tooth without
      ferrule. The CMP with NiCr alloy exhibited the highest stress distribution among
      other CMP. To avoid higher stress in teeth, alloys of Au, AgPd and CuAl,
      respectively, are recommended.

PMID- 29043867
TI  - Risk factors for surgery in patients with retention of endoscopic capsule.
AB  - OBJECTIVES: Surgery is still the main means for removing retained endoscopic
      capsules. This study intended to evaluate risk factors for surgery in patients
      with capsule retention. MATERIALS AND METHODS: The data of 5348 consecutive
      capsule endoscopy examinations were retrospectively analyzed. Cox regression
      analysis was used to evaluate risk factors. RESULTS: Seventy-seven patients
      (1.4%) had capsule retention. Spontaneous passage occurred in 16 patients, of
      which 14 were asymptomatic. Successful retrieval by double-balloon enteroscopy
      (DBE) was achieved in 14 patients, of which 11 did not need surgery during
      clinical follow-up. A total of 50 patients underwent surgery. The cumulative
      rates of surgery were 44.2%, 53.2%, 55.8%, 62.3% and 64.9% at 1, 3, 6, 12 and 60
      months after capsule retention, respectively. Intestinal obstruction [hazard
      ratio (HR) 2.05, 95% confidence interval (CI) 1.12-3.76; p = .020] and overt
      small bowel bleeding (HR 2.01, 95%CI 1.08-3.71; p = .027) during capsule
      retention were independently associated with an increased risk for surgery.
      Specific treatment for primary disease (HR 0.22, 95%CI 0.07-0.74, p = .014) and
      successful endoscopic retrieval (HR 0.20, 95%CI 0.06-0.66; p = .008) were
      independently associated with a decreased risk for surgery. CONCLUSIONS: For
      asymptomatic patients, specific medical treatment for primary disease can be
      maintained until the capsule spontaneously passes or symptoms appear. For
      patients with slight abdominal pain, DBE can be performed. For patients with
      intestinal obstruction or overt small bowel bleeding, early surgical consultation
      should be considered.

PMID- 29043868
TI  - Determinants of optimal bowel function in ileal pouch-anal anastomosis -
      physiological differences contributing to pouch function.
AB  - BACKGROUND: Variability in functional outcome after ileal-pouch anal anastomosis
      (IPAA) is to a large extent unexplained. The aim of this study was to perform
      multiple physiological and biochemical tests including an endoscopic examination
      with histology on IPAA patients with well and poorly functioning pouches to
      determine factors, or combinations thereof, contributing to functional outcome.
      METHODS: All patients with ulcerative colitis undergoing restorative
      proctocolectomy between 2000 and 2013 (N = 108) were interviewed using a pouch
      functioning score. The best and worst functioning quartiles were invited to
      undergo examination with a barostat measuring pouch volume at preset variable
      distension pressures, and a pouch endoscopy. RESULTS: Forty five of 58 eligible
      patients agreed to participate. The most significant physiological parameter
      differing between the well and poorly functioning pouches was pouch volume at
      first sensation, urge and discomfort (p value <.001). Urge volumes were 213 (CI
      171-256) ml for poorly and 352 (CI 305-401) ml for well functioning pouches.
      Pouchitis episodes were negatively correlated to function. The poorly functioning
      patients had a higher prevalence of histological signs of inflammation and hand
      sewn anastomosis, and a longer remaining rectal cuff, however, nonsignificant.
      The pouch pressure at sensation thresholds did not differ between the groups.
      CONCLUSIONS: Pouch volume is the most dominant predictor of pouch function in
      this study. The present comprehensive study of a multitude of different factors
      that possibly could be contributing to functional outcome, failed to shed much
      further light on the functional variability among pouch patients. The pouch
      physiology remains to a large extent unexplained.

PMID- 29043869
TI  - Identifying the biomarker potential of telomerase activity and shelterin complex
      molecule, telomeric repeat binding factor 2 (TERF2), in multiple myeloma.
AB  - Telomere length (TL) is maintained by telomere capping protein complex called
      shelterin complex. We studied the possible involvement and biomarker potential of
      shelterin complex molecules in naive multiple myeloma (MM) patients and controls.
      TL, relative telomerase activity (RTA), real-time PCR and Western blotting were
      performed in bonemarrow sample of 70 study subjects (patients = 50; controls =
      20). Significantly lowered mean TL, increased RTA and higher mRNA expression of
      shelterin molecules were observed in patients, while PIN2/TERF1 interacting
      telomerase inhibitor 1 (PINX1) showed lower mRNA expression. Significantly
      increased protein expression of telomeric repeat binding factor 2 (TERF2),
      protection of telomeres 1, adrenocortical dysplasia homolog, Tankyrase 1 and
      telomere reverse transcriptase were observed in MM patients. Significant
      correlation was observed among genes and of genes with clinical parameters. In
      conclusion, our findings showed alteration of these molecules at mRNA and protein
      levels suggested their involvement in disease progression. Optimal sensitivity
      and specificity of TERF2 and RTA on receiver operating characteristics curve
      analysis and univariate analysis demonstrated their biomarkers potential in
      better prediction of disease course.

PMID- 29043870
TI  - Weekly subcutaneous injection of tocilizumab in patients with rheumatoid
      arthritis.

PMID- 29043871
TI  - A review of sarilumab for the treatment of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease
      predominantly affecting the peripheral diarthrodial joints. Sarilumab is a human
      monoclonal antibody against the IL-6 receptor-alpha. In Phase II and III clinical
      trials, sarilumab in the background of methotrexate showed superior clinical
      efficacy over placebo in RA patients with inadequate response to methotrexate or
      inadequate response or intolerance to TNF inhibitors. Sarilumab monotherapy also
      showed superior efficacy compared with adalimumab monotherapy in RA patients with
      inadequate response or intolerance to methotrexate. For safety, injection site
      reaction, neutropenia and elevation of liver enzymes and serum cholesterol were
      more commonly observed with sarilumab than with placebo. Overall, sarilumab is
      expected to serve as another useful antirheumatic drug against active RA.

PMID- 29043872
TI  - A rare case of polyglandular autoimmune syndrome type IIIc with primary antibody
      failure.
AB  - Primary antibody deficiency syndromes are a rare group of disorders present at
      any age, with complex polygenic disorders. We report the forth case of
      polyglandular autoimmune syndrome (PAS) type IIIc worldwide with complex clinical
      features and no family history of endocrine disorders or primary
      immunodeficiencies. Our patient, a 44-year-old Caucasian female was diagnosed
      with PAS type IIIc due to the presence of autoimmune thyroiditis, autoimmune
      alopecia diffusa and primary ovarian insufficiency, associated with
      lymphoproliferative disease and primary antibody failure. Treatment included
      lifelong intravenous immunoglobulin, supplements and antibiotics. The clinical
      complexity and rare occurrence made it challenging to determine diagnosis and
      provide better treatment for the patient. The current case provides an insight of
      the challenges to determine primary antibody failure signs in the presence of PAS
      which will further help to determine diagnosis and therapeutic treatment for PAS
      patients.

PMID- 29043873
TI  - The use of beeswax as heating element in non-electric infant incubator.
AB  - Non-electric infant incubators are needed in remote areas that have no access to
      electricity to reduce infant mortality nationwide. In previous studies, non
      electric infant incubators have been developed using phase change material of
      beeswax as the heating element. This study aims to improve the performance of
      beeswax non-electric infant incubator to obtain a more reliable and practical
      one. The design of the original beeswax cartridge in the form of copper boxes was
      modified into tubes of stainless steel. The geometry and location of the air
      holes were also modified. Wood that was previously used as the body material was
      replaced with polyurethane to reduce the weight of the incubator. The beeswax
      cartridges were heated using boiling water until the beeswax melted. For
      temperature measurement, five 0.5 mm k-type thermocouples were placed inside of
      the incubator according to the National Industrial Standard of SNI 16-4221. The
      beeswax cartridge arrangement was varied to obtain the best performance. The
      results showed that polyurethane provides infant incubator lighter and more
      practical to use. The new design of non-electric infant incubator was capable of
      providing a temperature of 32-36  degrees C for 2 h.

PMID- 29043874
TI  - The risk of occupational exposure to mercury vapor in some public dental clinics
      of Baghdad city, Iraq.
AB  - BACKGROUND: Dental workers are exposed to elevated levels of elemental mercury
      vapor substantially above the occupational exposure standards when placing or
      removing mercury/silver tooth restorations and disposing of mercury waste. This
      results in a significant increase in occupational exposure and risk of mercury
      intoxication. METHODS: To evaluate the occupational exposure of dental workers to
      amalgam in four dental clinics in Baghdad city, the concentrations of mercury
      vapor were measured seasonally from February to November 2016. Samples of blood
      and urine were collected from 30 dental workers (exposed individuals) and five
      non-occupationally exposed individuals. Biochemical parameters such as
      cholesterol, liver enzymes (alanine aminotransferase, aspartate aminotransferase
      and alkaline phosphatase), renal enzymes (urea and creatinine), total protein and
      reduced glutathione (GSH) were observed. RESULTS: The results indicated that
      mercury vapor levels varied from 84.7 +/- 18.67 to 609.3 +/- 238.90 ug/m3 and
      most concentrations were above the occupational exposure standards. The results
      of the biochemical parameters showed a significant increase in levels of
      cholesterol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
      and no significant increase in blood urea and creatinine in dental workers in
      comparison with unexposed persons (control). Although the results showed a
      significant reduction in the levels of glutathione and total protein, there was
      no significant decrease in the levels of alkaline phosphatase (ALP) in exposed
      dental workers when compared with non-occupationally exposed individuals.
      CONCLUSIONS: It is concluded that mercury vapor concentrations in the indoor air
      of some dental clinics in Baghdad city are high and exceed the OSHA
      STEL(Occupational Safety and Health Administration Short Term Exposure Limit).
      The present data showed that altered biochemical parameters can be used as
      efficient bioindicators for mercury toxicity.

PMID- 29043875
TI  - Consolidation therapy with decitabine and intermediate-dose cytarabine followed
      by HLA-mismatched peripheral blood stem cells infusion for older patients with
      acute myeloid leukemia in first remission.
AB  - This retrospective study tested the feasibility of decitabine (DAC) plus
      intermediate-dose cytarabine (ID-AraC) followed by HLA-mismatched granulocyte
      colony-stimulating factor (G-CSF)-mobilized peripheral donor blood stem cells
      (GPBSCs) infusion as consolidation treatment for older patients with acute
      myeloid leukemia (AML) in first complete remission (CR). A total of 23 patients
      received this regimen for 3 cycles (D-GPBSCs group), and the outcome was compared
      with that of 19 patients treated with repeated cycles of ID-AraC chemotherapy
      (chemo group). The two regimens were well tolerated. The median recovery times
      for neutrophils and platelets were shorter in D-GPBSCs group than in chemo group
      (p<.05). No graft-versus-host disease (GVHD) was observed in D-GPBSCs group. The
      2-year leukemia-free survival (LFS) and overall survival (OS) were better in D
      GPBSCs group (51.6 and 55.4%) than in chemo group (27.1 and 34.2%) (p = .047 and
      p = .056). These data suggest that DAC and ID-AraC followed by GPBSCs as a
      consolidation regimen may be a safe and promising option for older patients with
      AML.

PMID- 29043876
TI  - Comment on "Bedside teaching with unwell patients: Can it ever be appropriate?"

PMID- 29043877
TI  - The seven deadly sins writers of academic papers should avoid.

PMID- 29043878
TI  - The association between homocysteine and systemic sclerosis: A review of the
      literature and meta-analysis.
AB  - OBJECTIVES: The main objective of this study was to summarize the existing
      evidence and quantitatively evaluate whether serum/plasma levels of homocysteine
      (Hcy) were associated with sclerosis (SSc) diseases by performing a meta-analysis
      of previous studies. METHODS: PubMed, Elsevier ScienceDirect and Cochrane Library
      databases were used to obtain all relative published literatures. Stata version
      11.0 (StataCorp, College Station, TX) was used for statistical analysis. The
      effect size of each study was calculated by the standardized mean difference
      (SMD) with 95% confidence interval (CI) or quartiles. RESULTS: A total of eight
      studies including 475 cases and 265 controls were finally included in this meta
      analysis. We found significant between-study heterogeneity and conducted analyses
      using random-effects models. No significant association was found between the
      serum levels of Hcy and SSc (pooled SMD =1.382 MUmol/L, 95%CI = -0.442 to 3.206,
      p = .137), but there are two outlier studies that deviate significantly from most
      other studies, which made it difficult to generalize these results. After
      excluding these two studies, six studies were included in the meta-analysis. The
      results showed that the serum levels of Hcy in SSc were significantly higher than
      that in healthy controls (pooled SMD = 1.182MUmol/L, 95%CI = 0.230-2.134, p =
      .015). CONCLUSION: Serum/plasma levels of Hcy in SSc diseases were higher than
      that in healthy controls.

PMID- 29043879
TI  - Use of an objective structured clinical exam (OSCE) for early identification of
      communication skills deficits in interns.
AB  - INTRODUCTION: There is limited information about whether OSCE during GME
      orientation can identify trainee communication deficits before these become
      evident via clinical performance evaluations. METHODS: Ninety-seven interns
      matriculating to eight residency programs in six specialties at four hospitals
      participated in a nine-station communication skills OSCE. Ratings were based on
      the "Kalamazoo, adapted" communication skills checklist. Possible association
      with intern performance evaluations was assessed by repeated-measures logistic
      regression and ROC curves were generated. RESULTS: The mean OSCE score was 4.08
      +/- 0.27 with a range of 3.3-4.6. Baseline OSCE scores were associated with
      subsequent communication concerns recorded by faculty, based on 1591 evaluations.
      A 0.1-unit decrease in the OSCE communication score was associated with an 18%
      higher odds of being identified with a communication concern by faculty
      evaluation (odds ratio 1.18, 95% CI 1.01-1.36, p = 0.034). ROC curves did not
      demonstrate a "cut-off" score (AUC= 0.558). Non-faculty evaluators were 3-5 times
      more likely than faculty evaluators to identify communication deficits, based on
      1900 evaluations. CONCLUSIONS: Lower OSCE performance was associated with faculty
      communication concerns on performance evaluations; however, a "cut-off" score was
      not demonstrated that could identify trainees for potential early intervention.
      Multi-source evaluation also identified trainees with communication skills
      deficits.

PMID- 29043880
TI  - Concurrent therapy of chronic lymphocytic leukemia and Philadelphia chromosome
      positive acute lymphoblastic leukemia utilizing CD19-targeted CAR T-cells.

PMID- 29043881
TI  - Characterization of the mutational profile of 11 diffuse large B-cell lymphoma
      cell lines.
AB  - Investigation of cancer cell lines is important for oncology research to
      characterize and understand mechanisms of cellular signaling and survival
      strategies in cancer. We analyzed the mutational profile of 11 diffuse large B
      cell lymphoma (DLBCL) cell lines using a customized high throughput sequencing
      panel. We compared our data to previously published mutation data to better
      characterize these cell lines and establish consensus on the mutational status of
      some functionally relevant genes. With our targeted sequencing approach we
      detected 61 somatic mutations. The most frequently affected gene was TP53. MYD88
      mutations were only seen in activated B-cell like cell lines. Overall comparison
      across different datasets revealed that just around 38% of mutations are reliable
      and can be validated by at least two independent observations whereas 24% of
      mutations could not be validated. Our analysis reveals considerable discrepancies
      regarding the mutational profile of some well-established cell lines.

PMID- 29043882
TI  - Ovarian volume and PCOS: a controversial issue.
AB  - Polycystic ovarian syndrome (PCOS) is a common endocrinopathy. The Rotterdam
      criteria indicate four distinct phenotypes. In phenotypes with the typical
      ovarian morphology (ovarian volume >=10 ml) the sensibility to clomiphene citrate
      (CC) ovulation therapy was demonstrated inversely proportional to the ovarian
      volume. In this retrospective study we evaluated the influence of ovarian volume
      on the success rate of CC ovulation induction in women with anovulatory phenotype
      2 characterized only by the presence of hyperandrogenism and anovulation (ANOV +
      HA). Statistical analysis was conducted by stratifying patients both on the basis
      of CC dose (Group 1: n = 37, 50 mg; Group 2: n = 9, 100 mg; and Group 3: n = 12,
      150 mg) and on the basis of response to therapy. Eighty women were evaluated but
      overall only 58 women (72.5%) reached ovulation. In the phenotype studied, we
      didn't find any correlations between ovarian volume and the chance of ovulation
      with the gradient increase in CC; furthermore, ovarian volume was comparable in
      CC responders and non-responders. Our study has shown that in the phenotype 2
      examined, ovarian volume did not have any predictive value of the dosage required
      to induce ovulation. The significance of this result is discussed.

PMID- 29043883
TI  - Structural maintenance of chromosomes 4 is required for leukemia stem cell
      maintenance in MLL-AF9 induced acute myeloid leukemia.
AB  - The gene, structural maintenance of chromosomes 4 (SMC4) plays important role in
      chromosomes condensing and mitotic sister chromatid segregation, which has been
      revealed in regulating multiple cancer development and carcinogenesis. However,
      the role of SMC4 in acute myeloid leukemia (AML) propagation and its function in
      regulation of leukemia stem cells (LSCs) is not yet clear. Using an MLL-AF9
      induced AML mouse model, we demonstrated that down modulating of SMC4 expression
      could prolong the survival time of AML mice. Furthermore, we found that knockdown
      SMC4 expression decreased the proportion of LSCs and affected its leukemia
      initiating capacity. Cell cycle assay demonstrated that more LSCs were arrested
      in G0 phase by SMC4 knockdown. This activity was accompanied by increased
      expression of the Cdkn1a (P21) and Cdkn1b (P27) as well as decreased expression
      of CDK4. Therefore, our study revealed the critical role of SMC4 during AML
      progression and provided new insights into the mechanism of LSC maintenance.

PMID- 29043884
TI  - Guselkumab for psoriasis: a critical appraisal of Phase III studies.
AB  - Biologic therapies have raised the frontiers of accepted treatment efficacy for
      severe psoriasis. Guselkumab is an IgG1 monoclonal antibody that binds to the p19
      subunit and inhibits IL-23. In three Phase III randomized, active comparator and
      placebo controlled trials, guselkumab demonstrated superior efficacy and a
      comparable safety profile when assessed against adalimumab and ustekinumab.
      Critical appraisal highlighted uncertainties over risk of bias from missing
      details in the trial publications that would be overcome with the provision of
      accompanying trial protocols, as well as the need for a head-to-head trial
      against an IL-17 inhibitor. Overall, guselkumab is a promising addition to the
      biologic options for psoriasis due to its high efficacy, safe profile, low
      immunogenicity and efficacy in ustekinumab and adalimumab nonresponders.

PMID- 29043885
TI  - First Report of Hb Kent [beta37(C3)Trp->Cys (TGG>TGC) HBB: c.114G>C] in a Chinese
      Family.
AB  - We report a novel HBB: c.114G>C mutation in a Chinese family. This mutation
      resulted in a beta37(C3)Trp->Cys amino acid substitution and was synonymous with
      Hb Kent, a hemoglobin (Hb) variant that was reported exclusively in patients of
      European descent. Though Hb Kent has a normal oxygen affinity and molecular
      stability, it has a characteristic dual variant appearance on cellulose acetate
      electrophoresis (CAE) and high performance liquid chromatography (HPLC) caused by
      the posttranslational modification of cysteine. We also report the phenotypic
      expression of this variant when coinherited with the Southeast Asian (- -SEA)
      double alpha-globin gene deletion.

PMID- 29043886
TI  - Assessing the risk of alcohol-induced dose dumping from sustained-release oral
      dosage forms: in vitro-in silico approach.
AB  - Consumption of alcoholic beverages with sustained-release oral dosage forms may
      pose a risk to patients due to potential alcohol-induced dose dumping (ADD).
      Regulatory guidances recommend in vitro dissolution testing to identify the risk
      of ADD, but the question remains whether currently proposed test conditions can
      be considered biopredictive. The purpose of this study was to evaluate different
      dissolution setups to assess ADD, and the potential of combined in vitro-in
      silico approach to predict drug absorption after concomitant alcohol intake for
      hydrophilic and lipophilic sustained-release tablets containing ibuprofen or
      diclofenac sodium. According to the obtained results, the impact of ethanol was
      predominantly governed by the influence on matrix integrity, with the increase in
      drug solubility being less significant. Hydrophilic matrix tablets were less
      susceptible to ADD than lipophilic matrices, although the conclusion on
      formulation ethanol-vulnerability depended on the employed experimental
      conditions. In silico predictions indicated that the observed changes in drug
      dissolution would not result in plasma concentrations beyond therapeutic window,
      but sustained-release characteristics of the formulations might be lost. Overall,
      the study demonstrated that in vitro-in silico approach may provide insight into
      the effect of ADD on drug clinical performance, and serve as a tool for ADD risk
      assessment.

PMID- 29043887
TI  - Living with Low Vision: Strategies Supporting Daily Activity.
AB  - The purpose of this research was to describe the strategies that older adults
      with low vision use to support daily living. A descriptive qualitative study of
      10 older adults with low vision was conducted using semistructured, audio
      recorded interviews. The data was coded and grouped into categories, and the
      findings were summarized. Four major themes were identified: (a) device nonuse;
      (b) sensory strategies and devices; (c) environmental strategies; and (d)
      resourcefulness. Older adults with low vision try many devices and strategies to
      find the ones that allow them to participate in meaningful activity within their
      physical and social environment. These findings support the use of a client
      centered, multicomponent, problem-solving approach to low vision rehabilitation
      to maximize performance of daily activity despite declining vision.

PMID- 29043888
TI  - Effect of sound generator on tinnitus and hyperacusis.
AB  - OBJECTIVE: Sound generator (SG) plays a role as effective sound therapy of
      tinnitus retaining therapy (TRT) in patients with severe tinnitus (Category 1) or
      hyperacusis (Category 3). This study was performed to evaluate the therapeutic
      effect of SGs. METHODS: A total of 120 tinnitus patients who visited our tinnitus
      clinic and were treated with SG along with TRT from January 2008 to December 2016
      were included. The patients were divided into two groups by tinnitus category; 78
      patients of category 1 and 42 patients of category 3. Their medical records
      including questionnaires regarding tinnitus severity were retrospectively
      reviewed to evaluate the therapeutic effect of SGs on tinnitus and hyperacusis.
      RESULTS: Category 3 patients included more female patients, were younger than
      category 1 patients (p = .001), and were prescribed SG earlier due to their
      severe symptom of hyperacusis. (p = .004) All patients showed significant
      improvements on all categories of tinnitus visual analogue scale (VAS) scores and
      tinnitus handicap inventory (THI) scores after six months use of SG (p < .05).
      Loudness discomfort levels measured by pure tone audiometry were significantly
      improved in category 3 group after six months use of SGs. CONCLUSION: SG with TRT
      seems to be an effective treatment modality for all tinnitus patients, especially
      those with comorbid hyperacusis.

PMID- 29043889
TI  - Unconventional treatments for chronic inflammatory demyelinating polyneuropathy.
AB  - This article focuses on the unconventional treatments used in chronic
      inflammatory demyelinating polyneuropathy (CIDP). First line, evidence-based
      treatments for CIDP include corticosteroids, immunoglobulins and plasma
      exchanges. Several unproven treatments are however given in treatment-refractory
      disease or to reduce requirements in validated therapies for reasons of side
      effects/practical delivery/cost. Despite methodological issues, IFN-alpha,
      azathioprine and methotrexate have not been shown to be useful in randomized
      controlled trials. Cyclophosphamide, rituximab and, as final resort in highly
      selected cases, hematopoietic stem cell transplant may be options considered in
      severely disabled refractory patients. Debatably, azathioprine, methotrexate,
      cyclosporine and mycophenolate mofetil are still occasionally used, among others,
      in milder disease. Physical therapy may be of benefit in CIDP but is not
      systematically considered as an integral part of management strategies. Current
      literature relating to unconventional therapies in CIDP is reviewed here and the
      possible avenues that require consideration in severe refractory disease and less
      disabling forms are discussed.

PMID- 29043890
TI  - 'Yeah, I've grown; I can't go out anymore': differences in perceived risks
      between girls and boys entering adolescence.
AB  - This analysis is based on data from the Global Early Adolescent Study, which aims
      to understand the factors that predispose young people aged 10-14 years to
      positive or negative health trajectories. Specifically, interview transcripts
      from 202 adolescents and 191 parents across six diverse urban sites (Baltimore,
      Ghent, Nairobi, Ile Ife, Assuit and Shanghai) were analysed to compare the
      perceived risks associated with entering adolescence and how these risks differed
      by gender. Findings reveal that in all sites except Ghent, both young people and
      their parents perceived that girls face greater risks related to their sexual and
      reproductive health, and because of their sexual development, were perceived to
      require more protection. In contrast, when boys grow up, they and their parents
      recognised that their independence broadened, and parents felt that boys were
      strong enough to protect themselves. This has negative consequences as well, as
      boys were perceived to be more prone to risks associated with street violence and
      peer pressure. These differences in perceptions of vulnerability and related
      mobility are markers of a gender system that separates young women and men's
      roles, responsibilities and behaviours in ways that widen gender power imbalance
      with lifelong social and health consequences for people of both sexes.

PMID- 29043891
TI  - Rapidly progressive interstitial lung disease in a patient with anti-MDA5
      positive amyopathic dermatomyositis.

PMID- 29043892
TI  - Tofacitinib in the treatment of active rheumatoid arthritis in adults.
AB  - Tofacitinib, a pan Janus kinase inhibitor, has been investigated as monotherapy
      in patients naive to methotrexate and in methotrexate incomplete responders and
      in combination with disease-modifying antirheumatic drugs in antirheumatic drug
      incomplete responders and TNF inhibitor failures in the Phase II and III
      programs. The clinical trial program demonstrated efficacy and a reasonable
      safety profile in these disease populations that has led to the approval of
      tofacitinib 5 mg twice daily orally in many countries. The pharmacology,
      chemistry, pharmacokinetics, pharmacodynamics, efficacy and safety in the Phase
      II and III clinical trials, safety in the long-term extension studies and
      postmarketing safety reports are the focus of this review.

PMID- 29043893
TI  - Considerations on: 'Risk of bacterial vaginosis, Trichomonas vaginalis and
      Candida albicans infection among new users of combined hormonal contraception vs
      LNG-IUS'.

PMID- 29043894
TI  - Cognitive behavioural therapy halves the risk of repeated suicide attempts:
      systematic review.
AB  - Objective To study whether cognitive behavioural therapy decreases suicide
      attempts in people with previous suicide attempts. Design Systematic review and
      meta-analysis. Setting Randomised trials that compare cognitive behavioural
      therapy with treatment as usual. Participants Patients who had engaged in any
      type of suicide attempt in the six months prior to trial entry resulting in
      presentation to clinical services. Main outcome measure Suicide attempt. Results
      We included ten trials, eight from Cochrane reviews and two from our updated
      searches (1241 patients, 219 of whom had at least one new suicide attempt).
      Cognitive behavioural therapy compared to treatment as usual reduced the risk of
      a new suicide attempt; risk ratio 0.47; 95% confidence interval 0.30-0.73; p =
      0.0009; I2 = 57%. Only seven suicides were reported (3 versus 4). One trial had
      an unusually large effect; if this trial is excluded, the risk ratio becomes 0.61
      (0.46-0.80) and the heterogeneity in the results disappears (I2 = 0%).
      Conclusions Cognitive behavioural therapy reduces not only repeated self-harm but
      also repeated suicide attempts. It should be the preferred treatment for all
      patients with depression.

PMID- 29043896
TI  - Erratum.

PMID- 29043895
TI  - The quality of information.

PMID- 29043897
TI  - Role of fibrate drugs in the prevention of diabetic foot.

PMID- 29043900
TI  - The fall and rise of the NHS.

PMID- 29043902
TI  - Documenting the dramatic effects of operative treatment of mitral stenosis.

PMID- 29043903
TI  - Feminism, biomedicine and the 'reproductive destiny' of women in clinical texts
      on the birth control pill.
AB  - The birth control pill is one of the most popular forms of contraception in North
      America and has been a key player in women's rights activism for over 50 years.
      In this paper, I conduct a feminist deconstructive analysis of 12 biomedical
      texts on the birth control pill, published between 1965 and 2016. This study is
      situated amongst the feminist scholarship that challenges the representation of
      women's bodies in biomedicine. Findings suggest that clinical texts on the birth
      control pill continue to universalise women's lives and experiences, and
      essentialise them based on their reproductive capacities. One way the texts
      accomplish this is by making women absent or passive in the literature thereby
      losing concern for the diversity of their lives, interpretations and identities
      as more than reproductive beings. The consequence of such representations is that
      biomedical texts disseminate limited forms of knowledge, in particular concerning
      definitions of 'natural' and 'normal' behaviour, with important consequences for
      the embodied experiences of women.

PMID- 29043904
TI  - Effects of anesthesia with nitrous oxide on tympanoplasty outcomes: a randomized
      controlled trial.
AB  - OBJECTIVES: To investigate effects of nitrous oxide (N2O), as inhalational
      anesthetic agent, on tympanoplasty outcomes. METHODS: In this randomized
      controlled trial, patients were randomized into two groups: 39 patients who
      received N2O as an inhalant anesthesia and 47 patients who did not receive. All
      were operated on with standard type of ear surgery. The protocol for the two
      groups was identical. Before surgery baseline audiometry was performed.
      Postoperative audiological controls were carried out at 3 months. RESULTS: There
      was no statistically significant difference between two groups regarding graft
      outcomes. No significant differences were found between the two groups regarding
      air-bone gap or bone conduction hearing level. CONCLUSIONS: Nitrous oxide usage
      does not seem to have significant impact on graft or hearing outcome of patients
      undergoing surgical repair of tympanic membrane.

PMID- 29043905
TI  - The value of narrow band imaging combined with stroboscopy for the detection of
      applanate indiscernible early-stage vocal cord cancer.
AB  - BACKGROUND: Narrow band imaging (NBI) and stroboscopy are non-invasive techniques
      to detect the malignant lesions of the vocal cord. This study was to assess the
      diagnostic value of combined endoscopic analysis in the applanate indiscernible
      early-stage vocal cord cancer. METHODS: A total of 110 patients with 160
      suspicious vocal cord malignant lesions were included in this retrospective
      study. Stroboscopy was immediately performed after NBI and white light endoscopy
      (WLE) were performed in all patients. Excisional biopsy was performed to examine
      histopathology examination. RESULTS: We found that the diagnostic specificity and
      PPV were higher in the NBI and WLE combined with stroboscopy group than in the
      NBI and WLE group without stroboscopy (88.9% vs 72.5%, 88.4% vs 60.9%). However,
      the diagnostic sensitivity was not significantly different in those two groups
      (69.3% vs 67.7%). CONCLUSION: NBI and WLE combined with stroboscopy is a
      promising method to detect early-stage vocal cord cancer with the advantage of
      clinical feasibility and diagnostic specificity.

PMID- 29043906
TI  - Parkinson's disease and the quest for preclinical diagnosis: an interview with
      Professor Werner Poewe.
AB  - Werner Poewe speaks to Laura Dormer, Editorial Director: Professor Werner Poewe
      is Professor of Neurology and Director of the Department of Neurology at
      Innsbruck Medical University in Innsbruck, Austria. He held a Residency in
      Clinical Neurology and Psychiatry at the University of Innsbruck, Austria, from
      1977 to 1984. From 1984 to 1985 he teamed up with Gerald Stern and Andrew Lees as
      a British Council Research Fellow at University College and Middlesex Hospital's
      Medical School in London to perform clinical studies into levodopa-induced
      dystonia and pharmacokinetics of levodopa in naive versus L-Dopa treated
      Parkinson's disease. Following his return to Austria, he held a position as
      Senior Lecturer in the Department of Neurology at the University of Innsbruck
      (1986-1989) after which he took over as Professor of Neurology and Acting
      Director of the Department of Neurology at Virchow Hospital of the Free
      University of Berlin (1990-1994). Professor Poewe's main research interests in
      the field of movement disorders are focused on differential and early diagnosis
      of Parkinson's disease, its natural history and pharmacological treatment. He has
      been involved in the steering committees of numerous drug trials in different
      stages of Parkinson's disease for the past 20 years and has authored and
      coauthored more than 500 original articles and reviews in the field of movement
      disorders. Professor Poewe served as President of the Austrian Society of
      Neurology from 2002 to 2004 as well as President of the Austrian Parkinson's
      Disease Society from 1996 to 2009. He has been awarded honorary membership of the
      German Society of Neurology as well as the Japanese Society of Neurology. His
      awards include the Walther-Birkmayer-Prize of the Austrian PD Society, the
      Dingebauer-Prize of the German Neurological Society as well as the Research
      Excellence Award of Innsbruck Medical University. Professor Poewe served as
      President of the International Movement Disorder Society (MDS) from 2000 to 2002,
      during which period he initiated the creation of important MDS task forces
      related to the critique and development of rating scales and of evidence-based
      treatment reviews. In his presidency, fell the negotiations between the European
      Section of MDS and the European Federation of Neurological Societies that
      resulted in formal agreements about joint European congresses. This model served
      as an important underpinning of the success of the MDS European Section in the
      past 15 years. Professor Poewe took over as chair of the MDS European Section
      from 2011 to 2013 and has recently been made an honorary member of the MDS. He is
      currently active as member of the Managing Board of the Movement Disorder
      Scientific Panel of the European Academy of Neurology.

PMID- 29043907
TI  - Prescription pattern and awareness of disease and treatment in patients of
      Parkinson's disease.
AB  - AIM: This cross-sectional study aimed to evaluate the prescription pattern,
      awareness of disease and treatment in patients with Parkinson's disease (PD).
      MATERIALS & METHODS: A total of 100 PD patients, attending a tertiary care
      hospital in Mumbai were included. Prescriptions were analyzed and awareness was
      evaluated using a questionnaire. RESULTS: The mean number of anti-Parkinson
      agents (APA) prescribed was 1.52 +/- 0.65. Number of APA strongly correlated with
      disease duration (rho = 0.818; p < 0.001). Many APA were underutilized
      (prescribed daily dose/defined daily dose < 1). There was no awareness of all
      items on symptoms and alternative therapeutic options. Awareness of disease
      impairments (32%), long-term complications (28%), dosing regimen (46%) and follow
      up (36%) was poor. CONCLUSION: More than one APA is commonly prescribed in PD
      patients. Awareness of disease and treatment of PD is poor among the patients.

PMID- 29043909
TI  - British Journal of Biomedical Science in 2017: What have we learned?
AB  - In 2017 the British Journal of Biomedical Science published 35 articles in the
      various disciplines that comprise biomedical science. These were 6 reviews, 22
      original articles, 6 'In Brief' short reports and one guideline. Of these, the
      majority were in clinical chemistry (one review, six data papers), microbiology
      (one review, four data papers), cellular pathology (four data papers) and
      virology (one review, two data papers). There were two data papers in transfusion
      science, whilst haematology, cytopathology and immunology were each represented
      by one review and one data paper. Reflecting the increasing complexity of the
      laboratory, five data papers crossed barriers between traditional disciplines,
      and so may be described as multidisciplinary. The present report will summarise
      key aspects of these publications.

PMID- 29043910
TI  - Intersections of girl child marriage and family planning beliefs and use:
      qualitative findings from Ethiopia and India.
AB  - Child marriage and subsequent early first birth is a considerable social,
      economic and health concern, and a pervasive practice in sub-Saharan Africa and
      South Asia. This study explores barriers and facilitators to family planning
      among women and girls, and their marital decision-makers subsequent to receipt of
      child marriage prevention programmes in Ethiopia and India. In-depth interviews
      with 128 women and girls who were married as minors or who cancelled or postponed
      marriage as minors and their marital decision-makers were analysed using content
      analysis. Respondents identified social norms, including child marriage and
      pressure to have children, and lack of information as barriers to family
      planning. Benefits included delayed first birth and increased birth spacing,
      improved maternal and child health and girls' educational attainment. Respondents
      associated family planning use with delayed pregnancy and increased educational
      attainment, particularly in Ethiopia. Child marriage prevention programmes were
      identified as important sources of family planning information. Ethiopia's school
      based programme strengthened access to health workers and contraception more so
      than India's community-based programme. Findings highlight young wives'
      vulnerability with regard to reproductive control, and support the need for multi
      sector approaches across communities, schools and community health workers to
      improve family planning among young wives.

PMID- 29043908
TI  - Early Functional Connectome Integrity and 1-Year Recovery in Comatose Survivors
      of Cardiac Arrest.
AB  - Purpose To assess whether early brain functional connectivity is associated with
      functional recovery 1 year after cardiac arrest (CA). Materials and Methods
      Enrolled in this prospective multicenter cohort were 46 patients who were
      comatose after CA. Principal outcome was cerebral performance category at 12
      months, with favorable outcome (FO) defined as cerebral performance category 1 or
      2. All participants underwent multiparametric structural and functional magnetic
      resonance (MR) imaging less than 4 weeks after CA. Within- and between-network
      connectivity was measured in dorsal attention network (DAN), default-mode network
      (DMN), salience network (SN), and executive control network (ECN) by using seed
      based analysis of resting-state functional MR imaging data. Structural changes
      identified with fluid-attenuated inversion recovery and diffusion-weighted
      imaging sequences were analyzed by using validated morphologic scales. The
      association between connectivity measures, structural changes, and the principal
      outcome was explored with multivariable modeling. Results Patients underwent MR
      imaging a mean 12.6 days +/- 5.6 (standard deviation) after CA. At 12 months, 11
      patients had an FO. Patients with FO had higher within-DMN connectivity and
      greater anticorrelation between SN and DMN and between SN and ECN compared with
      patients with unfavorable outcome, an effect that was maintained after
      multivariable adjustment. Anticorrelation of SN-DMN predicted outcomes with
      higher accuracy than fluid-attenuated inversion recovery or diffusion-weighted
      imaging scores (area under the receiver operating characteristic curves,
      respectively, 0.88, 0.74, and 0.71). Conclusion MR imaging-based measures of
      cerebral functional network connectivity obtained in the acute phase of CA were
      independently associated with FO at 1 year, warranting validation as early
      markers of long-term recovery potential in patients with anoxic-ischemic
      encephalopathy. (c) RSNA, 2017.

PMID- 29043911
TI  - Dutch courage? Effects of acute alcohol consumption on self-ratings and observer
      ratings of foreign language skills.
AB  - AIMS: A popular belief is that alcohol improves the ability to speak in a foreign
      language. The effect of acute alcohol consumption on perceived foreign language
      performance and actual foreign language performance in foreign language learners
      has not been investigated. The aim of the current study was to test the effects
      of acute alcohol consumption on self-rated and observer-rated verbal foreign
      language performance in participants who have recently learned this language.
      METHODS: Fifty native German speakers who had recently learned Dutch were
      randomized to receive either a low dose of alcohol or a control beverage that
      contained no alcohol. Following the experimental manipulation, participants took
      part in a standardized discussion in Dutch with a blinded experimenter. The
      discussion was audio-recorded and foreign language skills were subsequently rated
      by two native Dutch speakers who were blind to the experimental condition
      (observer-rating). Participants also rated their own individual Dutch language
      skills during the discussion (self-rating). RESULTS: Participants who consumed
      alcohol had significantly better observer-ratings for their Dutch language,
      specifically better pronunciation, compared with those who did not consume
      alcohol. However, alcohol had no effect on self-ratings of Dutch language skills.
      CONCLUSIONS: Acute alcohol consumption may have beneficial effects on the
      pronunciation of a foreign language in people who have recently learned that
      language.

PMID- 29043912
TI  - Latina young adults' use of health care during initial months in the United
      States.
AB  - We examined social ecological predictors of health care utilization among Latina
      young adults during their initial year after immigration to the United States.
      Participants were 530 Latinas (ages 18-23) who immigrated to Miami-Dade County,
      Florida, 11.5 months before assessment. We used multiple logistic regression to
      test predictors of health care usage. Approximately 36% utilized care. Dimensions
      of marianismo differentially associated with usage. Usage also was more likely
      for participants who reported more social network attachment, better health,
      greater neighborhood cohesion, and possessed a job and health insurance. Findings
      inform interventions to increase health care usage globally among women after
      immigration.

PMID- 29043913
TI  - Trust in Supervisor and Job Engagement: Mediating Effects of Psychological Safety
      and Felt Obligation.
AB  - In the social context of job engagement, the role of trust in supervisor in
      predicting engagement of employees has received attention in research. Very
      limited research, however, has investigated the mechanisms mediating this dynamic
      relationship. To address this important gap in knowledge, the aim of this study
      was to examine psychological safety and felt obligation as two psychological
      mechanisms mediating the effect of trust in supervisor on job engagement. Drawing
      from job engagement and social exchange theories, the mediating roles of
      psychological safety and felt obligation in the trust-engagement relationship
      were empirically investigated in the Malaysian context. Using self-report
      questionnaires, data were collected from 337 nurses employed in a public hospital
      located near Kuala Lumpur, Malaysia. Results fully supported the proposed serial
      multiple mediator model. Trust in supervisor was indirectly related to job
      engagement via psychological safety followed by felt obligation. This study
      provides empirical evidence that trust in supervisor makes employees feel
      psychologically safe to employ and express their selves in their job roles. This
      satisfaction of the psychological safety need is interpreted by employees as an
      important socioemotional benefit that, in turn, makes them feel obligated to pay
      back to their organization through their enhanced level of job engagement.
      Implications for theory and practice were discussed.

PMID- 29043914
TI  - Authors reply to Letter to the Editor- In response to: Comment on Durrani et
      al."s "Adalimumab for Ocular Inflammation".

PMID- 29043915
TI  - Corrigendum: Beyond Purity: Moral Disgust Toward Bad Character.
AB  - Original article: Giner-Sorolla, R., & Chapman, H. A. (2017). Beyond purity:
      Moral disgust toward bad character. Psychological Science, 28, 80-91.
      doi:10.1177/0956797616673193 In this article, some effect sizes in the Results
      section for Study 1 were reported incorrectly and are now being corrected. In the
      section titled Manipulation Checks: Act and Character Ratings, we reported a d
      value of 0.32 for the one-sample t test comparing participants' act ratings with
      the midpoint of the scale; the correct value is 0.30. The sentence should read as
      follows: Follow-up one-sample t tests using the midpoint of the scale as a test
      value (because participants compared John with Robert) indicated that the cat
      beater's actions were judged to be less wrong than the woman beater's actions,
      t(86) = -2.82, p = .006, d = 0.30. In the section titled Emotion Ratings, we
      reported a d value of 0.42 for the paired-samples t test comparing relative
      ratings of facial disgust and facial anger; the correct value is 0.34. In
      addition, the effect-size statistic is dz rather than d. The sentence should read
      as follows: As predicted, a paired-samples t test indicated that relative facial
      disgust ratings ( M = 4.36, SE = 0.21) were significantly different from relative
      facial-anger ratings ( M = 3.63, SE = 0.20), t(86) = -3.12, p = .002, dz = 0.34;
      this indicates that the cat-beater and woman-beater scenarios differentially
      evoked disgust and anger. Later in that section, we reported a d value of 0.21
      for the one-sample t test comparing ratings of facial disgust with the midpoint
      of the scale; the correct value is 0.20. In the same sentence, we reported a d
      value of 0.21 for the one-sample t test comparing ratings of facial anger with
      the midpoint of the scale; the correct value is 0.19. The sentence should read as
      follows: Follow-up one-sample t tests against the midpoint of the scale showed
      trends in the predicted directions, with higher disgust for the cat beater
      compared with the woman beater, t(86) = 1.7, p = .088, d = 0.20, and higher anger
      for the woman beater compared with the cat beater, t(86) = -1.82, p = .072, d =
      0.19 (see Fig. 1). These errors do not affect the significance of the results or
      the overall conclusions for Study 1.

PMID- 29043916
TI  - South Asian women's coping strategies in the face of domestic violence in the
      United States.
AB  - We conducted in-depth telephone interviews with a convenience sample of 20 South
      Asian women experiencing domestic violence in the United States. Utilizing the
      emotion-focused and problem-focused coping framework, the researchers analyzed
      the narratives of abused South Asian women. Emotion-focused coping strategies
      include (a) spirituality and/or religion and (b) the role of children. Problem
      focused coping strategies include (c) informal and formal support and (d)
      strategies of resisting, pacifying, safety planning. Implications for practice
      and future research in the United States and internationally are discussed.

PMID- 29043917
TI  - Parenting and Adolescents' Depressive Symptoms: The Mediating Role of Future Time
      Perspective.
AB  - This study investigated the relations between maternal and paternal rearing
      practices and adolescents' depressive symptoms, and whether time perspective in
      adolescence explains these links. The sample included 306 students (158 girls),
      aged between 10.83 and 14.42 years. Adolescents completed questionnaires
      assessing their perceptions of maternal and paternal acceptance and psychological
      control, and of their future time perspective and depressive symptoms.
      Adolescents who rated their mothers as more accepting and those who rated their
      fathers as less psychologically controlling also reported lower levels of
      depressive symptoms and greater future time perspective. Further, adolescents who
      had greater future time perspective reported lower levels of depressive symptoms.
      Finally, time perspective partially mediated the relations of maternal and
      paternal acceptance, and paternal control with depressive symptoms in
      adolescence. The findings highlight the unique relations of maternal acceptance
      and paternal psychological control with adolescents' depressive symptoms, and
      that future time perspective is one mechanism that might explain why parenting
      strategies are linked with depressive symptoms in adolescence.

PMID- 29043918
TI  - "Being able to speak": What individuals in jail perceived as helpful about
      participating in alcohol-related brief interventions.
AB  - BACKGROUND: A significant proportion of individuals within the criminal justice
      system meet criteria for a substance use disorder. Treatments for individuals who
      are incarcerated with substance use disorders show minimal to no benefit on
      postrelease outcomes, suggesting a need to improve their effectiveness,
      particularly those that can be delivered in a brief format. The purpose of this
      study was to describe what individuals in jail with substance use disorders
      perceived as being helpful about 2 brief alcohol-focused interventions, which can
      be used to inform future treatments with this population. METHODS: Data came from
      a parent study where 58 individuals in jail with substance use disorders received
      either a motivational or educational intervention focused on alcohol and other
      substance use and then completed a questionnaire assessing what was most and
      least helpful about the interventions. Qualitative responses were coded using a
      grounded theory approach. RESULTS: Results indicated that participants from both
      interventions reported that receiving individualized attention and talking one-on
      one with someone was helpful, and that the interventions were encouraging and
      elicited hope. There also were specific components from each intervention that
      participants said were beneficial, including the opportunity to discuss plans for
      postrelease and to learn about addiction from psychoeducational videos.
      Participants noted areas for improving future interventions. Suggestions from
      participants were to offer tangible resources upon release, make session lengths
      flexible, and reduce assessment burden during research interviews. CONCLUSIONS:
      Findings align with established approaches for working with marginalized groups,
      namely, community-based participatory research methods and shared decision-making
      models for treatment. This study provided a voice to individuals in jail with
      substance use disorders, a group often underrepresented in the literature, and
      may offer an initial look at how to improve treatments for this high-risk
      population.

PMID- 29043919
TI  - Beyond survival: 5-year neurodevelopmental follow-up of a cohort of preterm
      infants in Colombo, Sri Lanka.
AB  - BACKGROUND: There is a lack of information on long-term neurodevelopmental
      outcome in preterm neonates in low- and middle-income countries. OBJECTIVES: To
      describe the developmental attainments of preterm neonates followed up for 5
      years and to identify the risk factors for impairment. METHOD: A prospective
      descriptive cohort study was undertaken in neonates of 34 weeks gestation born
      within a period of 12 months at a single tertiary maternity and neonatal unit in
      Colombo, Sri Lanka. Infants were assessed for neurodevelopment using the Bayley
      Infant and Toddler III(r) Assessments at 6, 12 and 24 months of corrected age and
      school readiness assessment at 5 years. RESULTS: Fifty-one infants were assessed
      at least once, 45 were assessed at 2 years and 39 had a final assessment at 5
      years. Neurodevelopmental attainment deteriorated significantly in the cognitive
      and motor composite scores from 6 to 24 months (p < 0.05). By 5 years the number
      of children with delay in cognitive, language and motor domains had reduced
      significantly from 24 months (p < 0.05) but the cognitive skills remained most
      affected (10/39). At 5 years, 13 of 39 children had a confirmed diagnosis of a
      neurodevelopmental disorder: eight had attention deficit hyperactivity disorder,
      three autism spectrum disorder, one cerebral palsy and one visual impairment.
      Surfactant administration and retinopathy of prematurity were the most
      significant risks for delayed development at 5 years (p < 0.05). CONCLUSION:
      Deterioration of cognitive and motor composite scores over the first 24 months
      highlights the need for regular surveillance of premature infants. There was a
      discrepancy between the diagnosis of neurodevelopmental delay at 24 months and at
      5 years. But the notable impact on school readiness skills requires public health
      initiatives to cater for the needs of these children.

PMID- 29043920
TI  - Simultaneity of leisure behaviors and common mental disorders among healthcare
      workers.
AB  - The objective of this study was to investigate the aggregation of four leisure
      behaviors and the association between the number of leisure behaviors and common
      mental disorders (CMD). A cross-sectional study was carried out with a
      representative sample of healthcare workers of Brazil. The aggregation of the
      types of leisure activities was assessed by comparing the observed prevalence
      with the expected prevalence. The logistic regression analysis evaluated the
      association between the number of leisure behaviors and CMD. Leisure behaviors
      tended to show aggregation (<0.05). The multivariate analysis showed a negative
      association between the number of leisure behaviors and the CMD, only among
      women. The results indicate that the association between the number of leisure
      behaviors and the CMD is different depending on sex.

PMID- 29043921
TI  - Adaptation of the Barkin scale of maternal functioning and examination of the
      psychometric properties.
AB  - Evaluation of the maternal function is important not only for the mother and the
      baby but for the family health, as well. The aim of the researchers was to
      examine the Barkin Index of Maternal Function (BIMF) to Turkish Culture. Two
      hundred thirty-five postpartum women participated in the study. As a result of
      exploratory factor analysis of the scale, we decided that it should be 5-factor.
      Fit indexes of confirmatory factor analysis (CFA) were determined as Root Mean
      Square Error of Approximation (RMSEA) 0.05, Non-normed Fit Index (NNFI) 0.94,
      Comparative Fit Index (CFI) 0.96, and Goodness of Fit Index (GFI) 0.91. Overall,
      Cronbach's alpha reliability coefficient of the scale was 0.73. BIMF was
      determined as a reliable and valid tool for Turkish society. Since giving birth
      to a baby is related not only with the new mother but also with her relatives, it
      is one of the biggest change eras in a woman's life. This new era brings new
      changes into the mother's life in terms of physical, psychological, social, and
      spiritual aspects.

PMID- 29043922
TI  - Barriers and facilitators to dispensing of intranasal naloxone by pharmacists.
AB  - BACKGROUND: Although misuse of prescription opioids has reached epidemic
      proportions, pharmacy-based preventive services to combat this epidemic are
      limited. The aims of this study were to identify barriers and facilitators to the
      dispensing of intranasal naloxone (INN) by pharmacists in New Mexico. METHODS:
      For this mixed-methods study, a qualitative component (focus group) informed the
      development of a quantitative component (electronic survey) distributed to all
      pharmacists registered with the New Mexico Board of Pharmacy and practicing in
      the state. A 46-item survey included questions about pharmacists' concerns
      regarding dispensing INN, barriers and facilitators to dispensing INN, efforts
      needed to increase availability and utilization of pharmacist-dispensed INN, and
      characteristics of respondents and their pharmacies. RESULTS: Pharmacists from
      all geographical regions and all types of pharmacy settings were represented in
      the sample (final N = 390, participation rate 23.5%, including a subset of 182
      community pharmacists). The main barriers identified were (1) out-of-pocket costs
      for patients; (2) time constraints for pharmacists; and (3) inadequate
      reimbursement for pharmacists. The main facilitators were (1) increased awareness
      among opioid-using patients and family members about the need for INN; (2)
      additional education to the general public; and (3) additional training for
      pharmacists on how to initiate discussions about INN with high-risk patients.
      Some community pharmacists were concerned that INN dispensing would promote
      opioid abuse (16.5%) and attract undesirable clientele (14.3%). In a
      multivariable logistic regression analysis of a community pharmacy subset, a
      higher number of concerns about INN (odds ratio [OR] = 0.87; 95% confidence
      interval [CI]: 0.82-0.93) and a pharmacy setting in a chain grocery or a "big
      box" store (OR = 0.38; 95% CI: 0.16-0.92) were associated with decreased odds of
      dispensing INN. CONCLUSIONS: Effective intervention strategies for increasing
      dispensing of intranasal naloxone by pharmacists should focus on pharmacists'
      concerns, include education to multiple audiences, and address provider-level,
      system-level, and society-level barriers.

PMID- 29043925
TI  - Filipino therapists' experiences and attitudes of interprofessional education and
      collaboration: A cross-sectional survey.
AB  - For the past more than 50 years, the World Health Organisation has acknowledged
      through empirical findings that health workers that learn together work together
      effectively to provide the best care for their patients. This study aimed to: (1)
      describe the perceived extent of interprofessional education (IPE) experience
      among Filipino occupational therapists (OTs), physical therapists (PTs), and
      speech-language-pathologists (SLPs); (2) identify their attitudes towards
      interprofessional collaboration (IPC); and (3) compare their attitudes towards
      IPC according to: prior IPE experience, classification of IPE experience,
      profession, years of practice, and practice setting. Using a cross-sectional
      survey design, a two-part questionnaire was sent to Filipino OTs, PTs, and SLPs
      working in the Philippines via an online survey application. The first part of
      the survey contained eight items of demographic information and the second part
      contained the 14-item Attitudes Towards Health Care Teams Scale (ATHCTS).
      Findings revealed that among the Filipino OT, PT and SLP respondents (n = 189),
      70.9% had prior experience on IPE. Moreover, the three most commonly used IPE
      teaching-learning strategies were case discussion (clinical setting), small group
      discussion, didactics, and case discussion (community setting), while the use of
      didactics and case discussion (community setting) yielded more agreeable
      attitudes towards IPC. Among the 14 items in the ATHCTS, 11 were rated with
      agreeability and three items with neutrality. For professional variables, only
      the practice setting variable yielded a statistically significant finding
      confirming those working in the academia to be more agreeable towards IPC
      compared to other settings. However, years of practice and professional
      background variables both yielded no statistically significant difference
      implying no association between years of practice and attitude towards IPC and a
      homogenous composition among respondents, respectively. The results of this
      research are to springboard IPE initiatives within Philippine higher education
      institutions to enable evidence-based IPC approaches in clinical practice.

PMID- 29043926
TI  - Efficient induction of apoptosis in cancer cells by paclitaxel-loaded selenium
      nanoparticles.
AB  - AIM: To develop selenium nanoparticles (SeNPs)-based delivery systems for
      paclitaxel (PTX) and assess their antiproliferative efficacy against cancer cells
      in vitro with potential mechanistic insight. METHODS: Pluronic F-127 stabilized
      SeNPs were prepared and characterized. Effects of PTX-loaded SeNPs on lung
      (A549), breast (MCF7), cervical (HeLa) and colon (HT29) cancer cells were studied
      by viability assay complemented with flow-cytometric analyses of cell cycle,
      apoptosis, mitochondrial membrane potential, intracellular reactive oxygen
      species and caspase activity. RESULTS: PTX-loaded SeNPs demonstrated significant
      antiproliferative activity against cancer cells. Cell cycle analyses of PTX-SeNPs
      treated cells established G2/M phase arrest in a dose-dependent manner leading to
      apoptosis. Further investigation revealed disruption of mitochondrial membrane
      potential orchestrated with induction of reactive oxygen species leading to the
      activation of caspases, key players of apoptotic cell death. CONCLUSION:
      Efficient induction of apoptosis in various cancer cells by PTX-loaded SeNPs,
      with appropriate future studies, might lead to potential anticancer strategies.

PMID- 29043927
TI  - A Comparative Pharmacokinetic Assessment of a Novel Highly Bioavailable Curcumin
      Formulation with 95% Curcumin: A Randomized, Double-Blind, Crossover Study.
AB  - OBJECTIVE: Curcumin exhibits many beneficial health-promoting characteristics.
      However, its poor oral absorption precludes its general use. This study assessed
      the bioavailability of a novel curcumin formulation compared to 95% curcumin and
      published results for various other curcumin formulations. METHODS: A randomized,
      crossover, double-blind, comparator-controlled pharmacokinetic study was
      performed in 12 healthy adult subjects to determine the appearance of free
      curcumin and its metabolites curcumin sulfate and curcumin glucuronide in plasma
      after a single dose of a novel proprietary curcumin liquid droplet micromicellar
      formulation (CLDM) and unformulated 95% curcumin powder in capsule form. An
      equivalent 400-mg dose of each product was administered. The 95% curcumin
      contained 323 mg curcumin, and the CLDM contained 64.6 mg curcumin. Blood samples
      were drawn and plasma was analyzed for curcumin and its 2 conjugates without
      enzymatic hydrolysis by liquid chromatography-tandem mass spectroscopy. RESULTS:
      Plasma levels of curcumin sulfate and curcumin glucuronide after 1.5 hours from
      CLDM were approximately 20 and 300 ng/mL, respectively, whereas the levels for
      95% curcumin were near baseline. Free curcumin reached a maximum level of 2 ng/mL
      for CLDM and 0.3 ng/mL for 95% curcumin at 1.5 hours. For the CLDM, a small
      secondary free curcumin peak occurred at 12 hours and a tertiary 1.5-ng/mL peak
      occurred at 24 hours. The total curcumin absorbed as represented by the area
      under the curve (AUC)/mg administered curcumin for CLDM was 522 times greater
      than for the 95% curcumin. CONCLUSIONS: The novel CLDM formulation facilitates
      absorption and produces exceedingly high plasma levels of both conjugated and
      total curcumin compared to 95% curcumin. A comparison of the Cmax/mg curcumin and
      AUC/mg of administered curcumin for CLDM with data from pharmacokinetic studies
      of various enhanced absorption formulations indicate that the greatest absorption
      and bioavailability are produced with the novel CLDM formulation.

PMID- 29043928
TI  - Using transcranial direct current stimulation to treat symptoms in mild cognitive
      impairment and Alzheimer's disease.
AB  - Transcranial direct current stimulation (tDCS) has recently been investigated as
      a potential nonpharmacological treatment for individuals with mild cognitive
      impairment (MCI) and Alzheimer's disease (AD). A comprehensive literature search
      was performed on tDCS studies published until March 2017 using MEDLINE, Embase
      and PsychINFO databases. 12 articles with a total of 202 MCI or AD participants
      were included. Although ten of the 12 studies demonstrated positive findings with
      tDCS, two studies reported no effect on cognition. There was a wide range of
      methodological approaches used and in the cognitive functions measured. The
      variability in treatment response may be related to the heterogeneity in
      stimulation parameters including the site of stimulation, and cognitive
      assessments used. Patient-related factors including individual psychological,
      biological, and physiological status at the time of stimulation may also
      influence treatment response. We recommend that more comparative studies using
      similar patient factors and study parameters are needed in order to better
      understand the efficacy of tDCS in MCI and AD.

PMID- 29043929
TI  - A survey-based study identifies common but unrecognized symptoms in a large
      series of juvenile Huntington's disease.
AB  - AIM: The symptoms of Huntington's disease are well known, yet the symptoms of
      juvenile Huntington's disease (JHD) are less established due to its rarity. The
      study examined a cluster of symptoms considered to be common, but under
      recognized in JHD: pain, itching, sleeping difficulties, psychosis and tics.
      MATERIALS & METHODS: A symptom survey was constructed using the online tool
      Qualtrics and dispersed to JHD caregivers through websites. RESULTS: A total of
      33 surveys were completed. Disrupted sleep was the most prevalent symptom (87%),
      followed by tics (78%), pain (69%), itching (60%) and psychosis (39%).
      CONCLUSION: Despite limitations, the study supports that there are symptoms in
      the JHD population that are not considered classic, however, are common and
      significant for patients and caregivers.

PMID- 29043930
TI  - Associations Among Fatty Acids, Desaturase and Elongase, and Insulin Resistance
      in Children.
AB  - OBJECTIVES: Fatty acid profiles and desaturase (SCD-16, SCD018, D5D, D6D) and
      elongase (ELOVL6) enzyme activity have been associated with adiposity and
      metabolic disease. While this has been studied in adults, few studies have
      included children. The objective of this study was to evaluate these markers in
      children and identify relationships with markers of metabolic health. It was
      hypothesized that these lipid markers would be correlated to adiposity and
      metabolic disease. METHODS: This study was a cross-sectional analysis of fourth-
      and fifth-grade children (n = 86, aged 9-12) participating in a comprehensive
      nutrition program. Any student enrolled in the program was eligible for inclusion
      in this study. Fasting plasma was collected and analyzed for total fatty acids,
      glucose, insulin, and full lipid panels. Insulin resistance was estimated using
      calculated homeostatic model assessment for insulin resistance (HOMA-IR) values.
      RESULTS: There were no differences in lipid markers, glucose, insulin, or HOMA-IR
      among children classified as normal weight, overweight, or obese. SCD-16, D5D,
      and ELOVL6 activity was significantly correlated to HOMA-IR values (r = 0.39, p =
      0.001; r = -0.33, p = 0.006; r = -0.37, p = 0.005, respectively). In regression
      analysis, body mass index for age percentile, D6D activity, ELOVL6 activity, and
      systolic blood pressure were the most significant predictors of HOMA-IR values
      (adjusted r2 = 0.39, p <= 0.001). CONCLUSIONS: There was no relationship between
      these lipid markers and adiposity in this population; however, there were
      correlations with HOMA-IR. Regardless of adiposity, there may be underlying
      changes in fatty acid and lipid metabolism associated with the development of
      metabolic diseases.

PMID- 29043932
TI  - Information Needs Assessment for K-12 School Nurses in Rural Eastern Washington
      State.
AB  - School nurses are an often-overlooked population of health care professionals who
      have great importance in rural communities where access to health care is
      limited. In order to better serve school nurses in rural eastern Washington, an
      assessment was conducted to determine their information needs, behaviors, and
      perceptions. Results indicated this population of school nurses searches for
      multiple types of health information on a daily basis and navigates obstacles to
      information access using a variety of resources. While largely confident in their
      searching ability, they are open to learning more about how to find reliable
      health information to support their daily responsibilities. These results will
      guide the development of a workshop for school nurses about using reliable health
      information resources to improve health care in their rural communities.

PMID- 29043933
TI  - Trip Database: Turning Research into Practice for Evidence-Based Care.
AB  - Trip Database is a freely available search engine based in the United Kingdom.
      Trip directs users to journal articles, practice guidelines, and other research
      to support evidence-based medical practice. This column includes sample searches
      in both the free version and in the subscription Pro version.

PMID- 29043935
TI  - An Analysis of Physician Assistant LibGuides: A Tool for Collection Development.
AB  - The Physician Assistant (PA) specialty encompasses many subject areas and
      requires many types of library resources. An analysis of PA LibGuides was
      performed to determine most frequently recommended resources. A sample of
      LibGuides from U.S. institutions accredited by the Accreditation Review
      Commission on Education for the Physician Assistant (ARC-PA) was included in this
      study. Resources presented on guides were tabulated and organized by resource
      type. Databases and point-of-care tools were the types of resources listed by the
      most LibGuides. There were over 1,000 books listed on the 45 guides, including
      over 600 unique books listed. There were fewer journals listed, only 163.
      Overall, while the 45 LibGuides evaluated list many unique resources in each
      category, a librarian can create an accepted list of the most frequently listed
      resources from the data gathered.

PMID- 29043936
TI  - Providing Health Sciences Services in a Joint-Use Distributed Learning Library
      System: An Organizational Case Study.
AB  - The purpose of this organizational case study is to describe the complexities
      librarians face when serving a multi-campus institution that supports both a
      joint-use library and expanding health sciences academic partnerships. In a
      system without a centralized health science library administration, liaison
      librarians are identifying dispersed programs and user groups and collaborating
      to define their unique service and outreach needs within a larger land-grant
      university. Using a team-based approach, health sciences librarians are
      communicating to integrate research and teaching support, systems differences
      across dispersed campuses, and future needs of a new community-based medical
      program.

PMID- 29043940
TI  - Using Maps to Promote Data-Driven Decision-Making: One Library's Experience in
      Data Visualization Instruction.
AB  - Data play a crucial role in health research, education, and patient care.
      Initiatives such as Big Data to Knowledge (BD2K) and Precision Medicine point to
      the increasing focus and value of data use and reuse. As the universe of data
      continues to grow exponentially, health education needs to provide students with
      practical hands-on learning sessions that illustrate the multitude of uses for
      data and statistics. Giving students early exposure to data reuse provides a
      solid background for the more complex data they may gather later in their
      education. This column describes how librarians at a general academic library
      used data dashboards and Tableau in two library sessions to provide students with
      hands-on experience in data visualization and its role in decision-making.

PMID- 29043938
TI  - Piloting Consumer Health Information Services in Collaboration with a Community
      Research Engagement Program.
AB  - At an academic health science center, librarians partnered with a community
      research engagement program to offer a suite of consumer health information
      services. The services included training staff in the use of online consumer
      health resources, purchasing a print collection of monographs, and creating a
      guide to both the online and print resources for staff use. Focus groups were
      conducted to assess information needs, and the workshop attendees' online health
      information competency was assessed presession and postsession. This article
      details planning and intervention efforts, and proposes future activities to meet
      the information needs of HealthStreet and its clients.

PMID- 29043942
TI  - The Librarian's Contribution to Continuing Medical Education.
AB  - At many hospitals, including Robert Wood Johnson (RWJ) University Hospital
      Rahway, librarians facilitate continuing medical education (CME) programs,
      sometimes working in that capacity as much as in their traditional librarian
      functions such as reference, research, cataloging, and bibliographic instruction.
      This column traces the relationship between the two aspects of the RWJ Rahway's
      CME coordinator and health sciences librarian's job to demonstrate that, because
      of their duties and skills, medical librarians can meaningfully contribute to
      hospitals' CME programs. The worlds of librarianship and CME are further
      connected by the same goal: the dissemination of information.

PMID- 29043943
TI  - Creating a Role for Embedded Librarians Within an Active Learning Environment.
AB  - In 2013, the librarians at a small academic health sciences library reevaluated
      their mission, vision, and strategic plan to expand their roles. The school was
      transitioning to a new pedagogical culture and a new building designed to
      emphasize interprofessional education and active learning methodologies.
      Subsequent efforts to implement the new strategic plan resulted in the librarians
      joining curriculum committees and other institutional initiatives, such as an
      Active Learning Task Force, and participating in faculty development workshops.
      This participation has increased visibility and led to new roles and
      opportunities for librarians.

PMID- 29043944
TI  - Courting Apocalypse: Creating a Zombie-Themed Evidence-Based Medicine Game.
AB  - In 2015, two librarians at the Hardin Library for the Health Sciences at the
      University of Iowa turned their dreams into a reality and secured funding to
      build a zombie-themed evidence-based medicine game. The game features a "choose
      your own adventure" style that takes students through a scenario where a disease
      outbreak is taking place and a resident is asked to use evidence-based medicine
      skills to select a screening and diagnostic tool to use on potentially infected
      patients. Feedback on the game has been positive, and future plans include
      building additional modules on therapy, harm, and prognosis.

PMID- 29043945
TI  - Merging Technology and Emotions: Introduction to Affective Computing.
AB  - Affective computing technologies are designed to sense and respond based on human
      emotions. This technology allows a computer system to process the information
      gathered from various sensors to assess the emotional state of an individual. The
      system then offers a distinct response based on what it "felt." While this is
      completely unlike how most people interact with electronics today, this
      technology is likely to trickle into future everyday life. This column will
      explain what affective computing is, some of its benefits, and concerns with its
      adoption. It will also provide an overview of its implication in the library
      setting and offer selected examples of how and where it is currently being used.

PMID- 29043946
TI  - Assessing the dimensionality of YFHS-Swe: a questionnaire to assess youth
      friendliness in differentiated health services.
AB  - The aim of this study was to assess the dimensionality of YFHS-Swe and identify
      possible unique factors in the evaluation of youth-friendliness. YFHS-Swe was
      answered by 1110 youths aged 16 to 25 years visiting youth clinics in Northern
      Sweden. Thirteen factors were identified by exploratory factor analysis and
      except for one factor they all proved to fit well and have good reliability when
      assessed by the confirmatory factor analysis. The YFHS-Swe proved to be credible
      and suitable for assessing youth-friendliness of differentiated health services
      in Sweden. With cultural and linguistic adaptations, it can be used in similar
      settings internationally.

PMID- 29043947
TI  - Outpatient continuing care after residential substance use disorder treatment in
      the US Veterans Health Administration: Facilitators and challenges.
AB  - BACKGROUND: In the U.S. Veterans Health Administration (VHA), residential
      treatment programs are an important part of the continuum of care for patients
      with substance use disorders (SUDs). Outpatient continuing care after residential
      treatment helps maintain early recovery and treatment gains. Knowing more about
      the drivers of variation in continuing care practices and performance across
      residential programs might inform quality improvement efforts. METHODS: Metrics
      of continuing care were operationalized and calculated for each of VHA's 63 SUD
      Residential Rehabilitation Treatment Programs (SUD RRTPs) and 34 Mental Health
      Residential Rehabilitation Treatment Programs (MH RRTPs) with a SUD track in
      fiscal year 2012. Management and frontline staff of these programs were then
      interviewed to learn what factors might contribute to high or low program
      performance on the metrics compared with national averages. RESULTS: Among SUD
      RRTPs, the mean rate of outpatient SUD/MH continuing care was 59% within 7 days
      and 80% within 30 days, and the mean rate of SUD continuing care was 63% within
      30 days. Among MH RRTPs with a SUD track, these rates were 56%, 75%, and 36%,
      respectively. There was substantial variability in continuing care rates across
      the 97 programs: 21%-93% for SUD/MH care within 7 days, 36%-100% for SUD/MH care
      within 30 days, and 4%-91% for SUD care within 30 days. Interviews with
      representatives of 44 programs revealed key facilitators of continuing care:
      accountability of program staff, predischarge scheduling, predischarge
      introductions to continuing care providers, strong patient relationships,
      accessibility, and persistent emphasis. Key challenges included inadequate
      program staffing, lack of program staff accountability, and poor accessibility.
      CONCLUSIONS: Wide variation in continuing care rates across programs and
      identification of common facilitators at high-performing programs suggest
      substantial opportunity for improvement for programs with lower performance.

PMID- 29043948
TI  - Editorial: Alzheimer's Disease: From Molecular Mechanisms to Psychobiological
      Perspectives.

PMID- 29043949
TI  - ARTHROSCOPIC SURGERY FOR KNEE OSTEOARTHRITIS: IMPACT OF HEALTH TECHNOLOGY
      ASSESSMENT IN GERMANY.
AB  - OBJECTIVES: This study aims to describe how a negative reimbursement decision
      based on the health technology assessment (HTA) report of a nondrug intervention
      affects healthcare providers in Germany. METHODS: Knee arthroscopy was chosen as
      an example, because as of April 2016 this procedure is no longer reimbursed for
      osteoarthritis, but is still covered for other indications, including meniscal
      lesions. The exclusion followed an HTA report prepared by the Institute for
      Quality and Efficiency in Health Care (IQWiG). Here, we examine how the decision
      to revoke reimbursement for arthroscopy was perceived by the surgical community.
      Information was collected from official hospital statistics, the internet, and
      informal interviews with orthopedic surgeons. RESULTS: In 2015, a total of 37,920
      arthroscopic procedures were performed for knee osteoarthritis in Germany.
      Several surgical societies were unhappy with the negative decision, which was
      issued as a directive in November 2015, and they challenged the decision-making
      process as well as the underlying scientific evidence. In March 2016, fifteen
      societies issued joint recommendations on how to differentiate osteoarthritis
      from other knee diseases and how to document other diseases in a way that
      inspections by representatives of health insurance funds would not detect any
      deficiencies. In informal interviews, orthopedic surgeons indicated that
      miscoding of the principal diagnosis (meniscal tear rather than knee
      osteoarthritis) is to be expected, especially in the hospital sector.
      CONCLUSIONS: HTA can have a significant impact on the provision of health
      services, but various loopholes allow physicians to undermine policy decisions.
      Therefore, it is important to involve all stakeholders in HTA and to convince
      them of the benefits of evidence-based medicine.

PMID- 29043950
TI  - Mangrovitalea sediminis gen. nov., sp. nov., a member of the family
      Alteromonadaceae isolated from mangrove sediment.
AB  - A Gram-stain-negative, facultative anaerobic and oligotrophic, rod-shaped, and
      motile with single polar flagellum bacterial strain, designed M11-4T was isolated
      from mangrove sediment in Yunxiao Mangrove National Nature Reserve, China. Growth
      was observed at temperatures from 10 to 40  degrees C (optimum 30  degrees C), at
      salinities from 0.5 to 6 % (optimum 2-3 %), and at pH from 5 to 8 (optimum 6).
      Phylogenetic analysis based on 16S rRNA gene sequence revealed that strain M11-4T
      shared highest sequence similarity with the genus Marinobacter(92.5-95.0 %) and
      represented a distinct phylogenetic lineage in the family Alteromonadaceae. The
      G+C content of the genomic DNA was 58.2 mol%. The dominant fatty acids were C16 :
      0, C16 : 0 N-alcohol, summed feature 9 (comprising iso-C17 : 1omega9c and/or C16
      : 0 10-methyl) and summed feature 3 (comprising C16 : 1omega7c and/or C16 :
      1omega6c). The predominant respiratory quinone was ubiquinone-9 and the major
      polar lipids were diphosphatidylglycerol; phosphatidylethanolamine;
      phosphatidylglycerol and an unidentified aminophospholipid. According to its
      morphology, physiology, fatty acid composition and 16S rRNA gene sequence
      analysis, the strain M11-4T should be assigned as a novel species of a novel
      genus for which the name Mangrovitalea sediminis gen. nov., sp. nov. is proposed.
      The type strain of Mangrovitalea sediminis is M11-4T (=MCCC 1K03312T=JCM 32104T).

PMID- 29043951
TI  - Verrucosispora endophytica sp. nov., isolated from the root of wild orchid
      (Grosourdya appendiculata (Blume) Rchb.f.).
AB  - A novel endophytic filamentous bacterium strain A-T 7972T, was isolated from wild
      orchid Grosourdya appendiculata (Blume) Rchb.f. collected in Thailand. The
      bacterium developed single non-motile spores with warty surface on substrate
      mycelia. The taxonomic position was described using a polyphasic approach. The
      16S rRNA gene sequence and phylogenetic analysis indicated that strain A-T 7972T
      belonged to the genus Verrucosispora and shared the highest sequence similarity
      with V. lutea YIM 013T (98.71 %) and V. gifhornensis DSM 44337T (98.53 %). The
      values of DNA-DNA relatedness that distinguished this novel strain from its
      closest species were below 70 %. The cell-wall peptidoglycan contained meso
      diaminopimelic acid. The whole-cell sugars were mannose, ribose, glucose and
      xylose. The predominant menaquinone was MK-9(H4). The predominant fatty acids
      were branched fatty acids iso-C15 : 0 and iso-C16 : 0. The diagnostic
      phospholipids profile consisted of phosphatidylethanolamine,
      diphosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannosides.
      The G+C content of the genomic DNA was 70.5 mol%. Based on its phenotypic,
      chemotaxonomic and genotypic characteristics, the new isolate A-T 7972T (=BCC
      50981T=TBRC 6031T=NBRC 112512T) is proposed to be the type strain of novel
      species, Verrucosispora endophytica sp. nov.

PMID- 29043952
TI  - Tenacibaculum agarivorans sp. nov., an agar-degrading bacterium isolated from
      marine alga Porphyra yezoensis Ueda.
AB  - A novel Gram-stain-negative, aerobic, rod-shaped, non-flagellated and agar
      digesting marine bacterium, designated as HZ1T, was isolated from the marine alga
      Porphyra yezoensis Ueda (AST58-103) collected from the coastal area of Weihai, PR
      China. Phylogenetic analysis based on 16S rRNA gene sequences placed HZ1T in the
      genus Tenacibaculum, and it formed a distinct clade in the phylogenetic tree with
      the type strains of Tenacibaculum amylolyticum and Tenacibaculum skagerrakense,
      with 97.0 % and 96.7 % 16S rRNA gene sequence similarities, respectively. The DNA
      G+C content of the isolate was 31.8 mol%. HZ1T contained MK-6 as the predominant
      menaquinone and iso-C15 : 0, summed feature 3 (C16 : 1omega7c and/or C16 :
      1omega6c), iso-C17 : 0 3-OH and iso-C15 : 1G as the major fatty acids. The major
      polar lipids were phosphatidylethanolamine, four unidentified lipids and five
      unidentified aminolipids. On the basis of the results of the phylogenetic
      analysis and phenotypic properties, it is concluded that HZ1T represents a novel
      species of the genus Tenacibaculum, for which the name Tenacibaculumagarivorans
      sp. nov. is proposed. The type strain is HZ1T (=MCCC 1H00174T=KCTC 52476T).

PMID- 29043953
TI  - Nonomuraea glycinis sp. nov., a novel actinomycete isolated from the root of
      black soya bean [Glycine max (L.) Merr].
AB  - A novel actinomycete, designated strain NEAU-BB2C19T, was isolated from the root
      of black soya bean [Glycine max (L.) Merr] collected from Harbin, Heilongjiang
      Province, China, and characterized using a polyphasic approach. The strain was an
      aerobic, Gram-stain-positive actinomycete that formed extensively branched
      substrate mycelium and aerial hyphae. The predominant menaquinones were MK-9(H2)
      and MK-9(H0). The major cellular fatty acid profile consisted of iso-C16 : 0, 10
      methyl C17 : 0 and 10-methyl C18 : 0. The polar lipid profile consisted of
      diphosphatidylglycerol, phosphatidylethanolamine, hydroxy
      phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside,
      phosphatidylglycerol and glycolipid. The DNA G+C content was 68.2+/-0.4 mol%.
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NEAU
      BB2C19T should be assigned to the genus Nonomuraea and formed a distinct branch
      with its closest neighbour Nonomuraea guangzhouensis NEAU-ZJ3T (98.75 % 16S rRNA
      gene sequence similarity). The morphological and chemotaxonomic properties of the
      strain were also consistent with those of members of the genus Nonomuraea. A
      combination of DNA-DNA hybridization results and some phenotypic characteristics
      indicated that strain NEAU-BB2C19T could be clearly differentiated from its
      closest phylogenetic relative. Thus, the strain is concluded to represent a novel
      species of the genus Nonomuraea, for which the name Nonomuraea glycinis sp. nov.
      is proposed. The type strain is NEAU-BB2C19T (=CGMCC 4.7430T=DSM 104838T).

PMID- 29043956
TI  - The amino-terminal domain of ELL transcription elongation factor is essential for
      ELL function in Schizosaccharomyces pombe.
AB  - Transcriptional elongation is a critical step for regulating expression of
      protein-coding genes. Multiple transcription elongation factors have been
      identified in vitro, but the physiological roles of many of them are still not
      clearly understood. The ELL (Eleven nineteen Lysine rich Leukemia) family of
      transcription elongation factors are conserved from fission yeast to humans.
      Schizosaccharomyces pombe contains a single ELL homolog (SpELL) that is not
      essential for its survival. Therefore to gain insights into the in vivo cellular
      functions of SpELL, we identified phenotypes associated with deletion of ell1 in
      S. pombe. Our results demonstrate that SpELL is required for normal growth of S.
      pombe cells. Furthermore, cells lacking ell1+ exhibit a decrease in survival when
      exposed to DNA-damaging conditions, but their growth is not affected under
      environmental stress conditions. ELL orthologs in different organisms contain
      three conserved domains, an amino-terminal domain, a middle domain and a carboxyl
      terminal domain. We also carried out an in vivo functional mapping of these
      conserved domains within S. pombe ELL and uncovered a critical role for its amino
      terminus in regulating all its cellular functions, including growth under
      different conditions, transcriptional elongation potential and interaction with
      S. pombe EAF. Taken together our results suggest that the domain organization of
      ELL proteins is conserved across species, but the in vivo functions as well as
      the relationship between the various domains and roles of ELL show species
      specific differences.

PMID- 29043954
TI  - N-acetylglucosamine affects Cryptococcus neoformans cell-wall composition and
      melanin architecture.
AB  - Cryptococcus neoformans is an environmental fungus that belongs to the phylum
      Basidiomycetes and is a major pathogen in immunocompromised patients. The ability
      of C. neoformans to produce melanin pigments represents its second most important
      virulence factor, after the presence of a polysaccharide capsule. Both the
      capsule and melanin are closely associated with the fungal cell wall, a complex
      structure that is essential for maintaining cell morphology and viability under
      conditions of stress. The amino sugar N-acetylglucosamine (GlcNAc) is a key
      constituent of the cell-wall chitin and is used for both N-linked glycosylation
      and GPI anchor synthesis. Recent studies have suggested additional roles for
      GlcNAc as an activator and mediator of cellular signalling in fungal and plant
      cells. Furthermore, chitin and chitosan polysaccharides interact with melanin
      pigments in the cell wall and have been found to be essential for melanization.
      Despite the importance of melanin, its molecular structure remains unresolved;
      however, we previously obtained critical insights using advanced nuclear magnetic
      resonance (NMR) and imaging techniques. In this study, we investigated the effect
      of GlcNAc supplementation on cryptococcal cell-wall composition and melanization.
      C. neoformans was able to metabolize GlcNAc as a sole source of carbon and
      nitrogen, indicating a capacity to use a component of a highly abundant polymer
      in the biospherenutritionally. C. neoformans cells grown with GlcNAc manifested
      changes in the chitosan cell-wall content, cell-wall thickness and capsule size.
      Supplementing cultures with isotopically 15N-labelled GlcNAc demonstrated that
      the exogenous monomer serves as a building block for chitin/chitosan and is
      incorporated into the cell wall. The altered chitin-to-chitosan ratio had no
      negative effects on the mother-daughter cell separation; growth with GlcNAc
      affected the fungal cell-wall scaffold, resulting in increased melanin deposition
      and assembly. In summary, GlcNAc supplementation had pleiotropic effects on cell
      wall and melanin architectures, and thus established its capacity to perturb
      these structures, a property that could prove useful for metabolic tracking
      studies.

PMID- 29043955
TI  - Lactobacillus allii sp. nov. isolated from scallion kimchi.
AB  - A novel strain of lactic acid bacteria, WiKim39T, was isolated from a scallion
      kimchi sample consisting of fermented chili peppers and vegetables. The isolate
      was a Gram-positive, rod-shaped, non-motile, catalase-negative and facultatively
      anaerobic lactic acid bacterium. Phylogenetic analysis of the 16S rRNA gene
      sequence showed that strain WiKim39T belonged to the genus Lactobacillus, and
      shared 97.1-98.2 % pair-wise sequence similarities with related type strains,
      Lactobacillus nodensis, Lactobacillus insicii, Lactobacillus versmoldensis,
      Lactobacillus tucceti and Lactobacillus furfuricola. The G+C content of the
      strain based on its genome sequence was 35.3 mol%. The ANI values between
      WiKim39T and the closest relatives were lower than 80 %. Based on the phenotypic,
      biochemical, and phylogenetic analyses, strain WiKim39T represents a novel
      species of the genus Lactobacillus, for which the name Lactobacillus allii sp.
      nov. is proposed. The type strain is WiKim39T (=KCTC 21077T=JCM 31938T).

PMID- 29043957
TI  - Rhodosalinus sediminis gen. nov., sp. nov., isolated from marine saltern.
AB  - A novel Gram-stain-negative, moderately halophilic, motile, facultatively
      anaerobic and rod-shaped strain, designated WDN1C137T, was isolated from a marine
      saltern at Wendeng, PR China. Optimal growth occurred at 40  degrees C, pH 7.5
      and with 7.0 % (w/v) NaCl. Q-10 was the sole respiratory quinone. The major
      cellular fatty acids (>10.0 %) in WDN1C137T were C18 : 1omega7c (46.2 %), cyclo
      C19 : 0omega8c (18.7 %) and C16 : 0 (12.3 %). The major polar lipids were
      phosphatidylglycerol, phosphoglycolipid, phosphatidylcholine, one unidentified
      glycolipid, one unidentified lipid, one unidentified aminolipid and two
      unidentified phospholipids. The genomic DNA G+C content was 70.9 mol%.
      Phylogenetic analysis based on 16S rRNA gene sequences revealed that WDN1C137T
      shared the highest similarity (94.5 %) to Roseivivax jejudonensis KCTC 42110T,
      followed by Roseivivax halodurans JCM 10272T (94.2 %) and Roseivivax roseus DSM
      23042T (94.1 %). WDN1C137T formed a separate branch from the closely related
      genera Roseivivax, Loktanella, Paracoccus and Cribrihabitans within the family
      Rhodobacteraceae, which indicated that it represented a novel genus in the
      phylogenetic tree. On the basis of the data from the current polyphasic study,
      the isolate is proposed to represent a novel species of a novel genus within the
      family Rhodobacteraceae, with the name Rhodosalinus sediminis gen. nov., sp. nov.
      The type strain of the type species is WDN1C137T (=KCTC 52478T=MCCC 1H00170T).

PMID- 29043958
TI  - Oceaniglobus indicus gen. nov., sp. nov., a member of the family Rhodobacteraceae
      isolated from surface seawater.
AB  - A Gram-stain-negative, non-motile, aerobic and heterotrophic strain, designated 1
      19bT, was isolated from surface seawater in the Indian Ocean. The cells were
      ovoid or coccus (0.8-1.0 um in diameter) with no flagellum. Activities of
      catalase and oxidase were positive. Growth was observed at salinity of 0.5-10
      (%NaCl, w/v) with an optimum of 3-4, at pH 5-10 with an optimum of 7-8, and at 5
      37  degrees C with an optimum of 28-35  degrees C. It accumulated poly-beta
      hydroxybutyrate granules inside the cell. Bacteriochlorophyll a was absent. The
      respiratory quinone was Q-10 and the dominant fatty acid was summed feature 8
      (C18 : 1omega7c and/or C18 : 1omega6c). The major polar lipids comprised
      phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine,
      diphosphatidylglycerol, an unidentified phospholipid and two unidentified polar
      lipids. Phylogenetic analysis based on 16S rRNA gene sequences revealed that
      strain 1-19bT belonged to the family Rhodobacteraceae and formed a distinct
      monophyletic clade with 'Oceaniovalibus guishaninsula' JLT2003 and Pontibaca
      methylaminivorans GRP21T, exhibiting similarities of 94.7 and 92.2 %,
      respectively. The genomic DNA G+C content was 64.2 mol%. Based on the phenotypic,
      chemotaxonomic and genotypic data, strain 1-19bT represents a novel species in a
      new genus of the family Rhodobacteraceae, for which the name Oceaniglobus indicus
      gen. nov., sp. nov. is proposed, with the type strain 1-19bT (=MCCC 1A11863T=KCTC
      52709T).

PMID- 29043959
TI  - Purified citritin in combination with vancomycin inhibits VRE in vitro and in
      vivo.
AB  - Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus
      (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) have been frequently
      associated with bacterial resistance mechanisms. These mechanisms, in turn,
      restrict a range of therapeutic opportunities for the treatment of infections
      caused by these micro-organisms. Faced with this problem, the present study aims
      to isolate and characterize molecules with antimicrobial activity derived from
      the fungus Penicillium citrinum isolated from Cerrado soil. Furthermore, we also
      tested possible antibacterial potential alone and in combination with commercial
      antimicrobial agents. In this context, citrinin was isolated and characterized by
      nuclear magnetic resonance and electrospray ionization. Functional analyses
      showed MIC of 128 ug ml-1 against S. aureus ATCC 25923, E. faecalis ATCC 29212
      and a clinical isolate of vancomycin-resistant E. faecium (VRE01). However, for a
      clinical strain of methicillin-resistant S. aureus (MRSA01), the MIC was 256 ug
      ml-1. In order to avoid such high concentrations and reduce the collateral
      effects, additive effects were evidenced by combining citrinin with cefoxitin
      against MRSA01 (FIC index=0.5) and also citrinin with vancomycin toward VRE01
      (FIC index=0.5). In vivo studies with BALB/c-tipe mice (MRSA assay) demonstrated
      a clinical ineffectiveness of cefoxitin associated with citrinin (9.8 mg kg-1 of
      cefoxitin +0.2 mg kg-1 of citrinin), with this combination being inefficient to
      increase animal survival. However, the combination used in the treatment of VRE
      (23.5 mg kg-1 of citrinin +1.5 mg kg-1 of vancomycin) sepsis model was extremely
      promising, leading to an animal survival rate of 80 percent. In summary, our data
      show, for the first time, the possible successful use of citrinin associated with
      vancomycin for pathogenic bacteria control.

PMID- 29043960
TI  - Surveillance of Zika virus infection in the EU/EEA, June 2015 to January 2017.
AB  - Surveillance of Zika virus (ZIKV) infection in the European Union/European
      Economic Area (EU/EEA) was implemented in 2016 in response to the large outbreak
      reported in the Americas in 2015 associated with an increased number of infants
      born with microcephaly. Between June 2015 and January 2017, 21 EU/EEA countries
      reported 2,133 confirmed cases of ZIKV infection, of whom 106 were pregnant
      women. Cases infected in the Caribbean constituted 71% of reported cases. Almost
      all cases (99%) were most probably infected by mosquito bite during travel
      outside continental Europe, while only 1% were transmitted sexually. Considering
      that 584 imported cases were reported between May and October 2016 among
      residents of areas with established presence of Aedes albopictus, the absence of
      autochthonous vector-borne cases suggests that Ae. albopictus is not an efficient
      vector for ZIKV infection.

PMID- 29043962
TI  - Usutu virus infections among blood donors, Austria, July and August 2017 -
      Raising awareness for diagnostic challenges.
AB  - Between July and August 2017, seven of 12,047 blood donations from eastern
      Austria, reacted positive to West Nile virus (WNV) in the cobas test (Roche).
      Follow-up investigations revealed Usutu virus (USUV) nucleic acid in six of
      these. Retrospective analyses of four blood donors diagnosed as WNV-infected in
      2016 showed one USUV positive. Blood transfusion services and public health
      authorities in USUV-endemic areas should be aware of a possible increase of human
      USUV infections.

PMID- 29043961
TI  - Low 2016/17 season vaccine effectiveness against hospitalised influenza A(H3N2)
      among elderly: awareness warranted for 2017/18 season.
AB  - In a multicentre European hospital study we measured influenza vaccine
      effectiveness (IVE) against A(H3N2) in 2016/17. Adjusted IVE was 17% (95%
      confidence interval (CI): 1 to 31) overall; 25% (95% CI: 2 to 43) among 65-79
      year-olds and 13% (95% CI: -15 to 30) among those >= 80 years. As the A(H3N2)
      vaccine component has not changed for 2017/18, physicians and public health
      experts should be aware that IVE could be low where A(H3N2) viruses predominate.

PMID- 29043964
TI  - Accuracy of diagnosis criteria in patients with suspected diagnosis of sporadic
      Creutzfeldt-Jakob disease and detection of 14-3-3 protein, France, 1992 to 2009.
AB  - Diagnostic criteria of Creutzfeldt-Jakob disease (CJD), a rare and fatal
      transmissible nervous system disease with public health implications, are
      determined by clinical data, electroencephalogram (EEG), detection of 14-3-3
      protein in cerebrospinal fluid (CSF), brain magnetic resonance imaging and prion
      protein gene examination. The specificity of protein 14-3-3 has been questioned.
      We reviewed data from 1,572 autopsied patients collected over an 18-year period
      (1992-2009) and assessed whether and how 14-3-3 detection impacted the diagnosis
      of sporadic CJD in France, and whether this led to the misdiagnosis of treatable
      disorders. 14-3-3 detection was introduced into diagnostic criteria for CJD in
      1998. Diagnostic accuracy decreased from 92% for the 1992-1997 period to 85% for
      the 1998-2009 period. This was associated with positive detections of 14-3-3 in
      cases with negative EEG and alternative diagnosis at autopsy. Potentially
      treatable diseases were found in 163 patients (10.5%). This study confirms the
      usefulness of the recent modification of diagnosis criteria by the addition of
      the results of CSF real-time quaking-induced conversion, a method based on prion
      seed-induced misfolding and aggregation of recombinant prion protein substrate
      that has proven to be a highly specific test for diagnosis of sporadic CJD.

PMID- 29043966
TI  - Hospital at home - a review of our experience.
AB  - INTRODUCTION: Hospital at home (HAH) is a service that provides home-based
      nursing and rehabilitation services whose aim is to prevent admission or to
      facilitate early discharge from care in an acute hospital. METHODS: We evaluated
      the effectiveness of early discharge hospital at home (HAH) schemes for hip
      fracture patients over a 27-year period in a district general hospital in the
      United Kingdom. A long-term database for audit and research purposes is
      maintained for all hip fracture patients admitted to Peterborough City Hospital.
      The data were analysed retrospectively and patients were followed up routinely
      for six weeks after discharge. RESULTS: As many as 8876 patients were admitted
      with a hip fracture between 1st January 1987 and 31st December 2014, of which
      5512 patients were eligible for one of the two available HAH schemes. The
      proportion of eligible patients discharged to the HAH schemes, and their hospital
      stay and readmission rates were measured; 1786 patients were discharged to a HAH
      scheme. The proportion of patients discharged to the scheme progressively reduced
      from a maximum of 94% to a minimum of 13% over the study period. The length of
      hospital stay until discharge to the scheme progressively increased from a mean
      of eight days to 18 days. DISCUSSION: We conclude that HAH schemes can
      potentially reduce the length of hospital stay of hip fracture patients but
      continued resources and service organisation have to be provided to match the
      increasing demand to prevent the service from becoming ineffective.

PMID- 29043965
TI  - Japanese Encephalitis Virus Transmitted Via Blood Transfusion, Hong Kong, China.
AB  - Japanese encephalitis virus (JEV) is a mosquitoborne virus endemic to China and
      Southeast Asia that causes severe encephalitis in <1% of infected persons.
      Transmission of JEV via blood transfusion has not been reported. We report
      transmission of JEV via blood donation products from an asymptomatic viremic
      donor to 2 immunocompromised recipients. One recipient on high-dose
      immunosuppressive drugs received JEV-positive packed red blood cells after a
      double lung transplant; severe encephalitis and a poor clinical outcome resulted.
      JEV RNA was detected in serum, cerebrospinal fluid, and bronchoalveolar lavage
      fluid specimens. The second recipient had leukemia and received platelets after
      undergoing chemotherapy. This patient was asymptomatic; JEV infection was
      confirmed in this person by IgM seroconversion. This study illustrates that,
      consistent with other pathogenic flaviviruses, JEV can be transmitted via blood
      products. Targeted donor screening and pathogen reduction technologies could be
      used to prevent transfusion-transmitted JEV infection in highly JEV-endemic
      areas.

PMID- 29043968
TI  - ?

PMID- 29043969
TI  - [Orthodontics and Alexis Schange in 1841].
AB  - INTRODUCTION: Alexis Schange was one of the first practitioners able to use
      accurate casts of the dental arches thanks to the invention of the impression
      tray by Delabarre. Consequently, his diagnoses were more precise and his
      appliances fitted better than those of his predecessors. MATERIALS AND METHOD:
      The author will first outline the status of Orthodontics prior to Schange and the
      advent of the first casts, before describing Schange's contribution to
      Orthodontics. DISCUSSION: In 1841, Schange published his "Handbook of Dental
      Uprighting", a clear and pedagogical work and undoubtedly the best over the many
      years when Orthodontics was exclusively European.

PMID- 29043970
TI  - [A change of paradigm in the treatment of Class II malocclusions in children and
      adolescents: the benefits of the Class II Corrector].
AB  - INTRODUCTION: The treatment of class II malocclusions is the core of our clinical
      activity. What elements can clinician rely on to offer their patients, whether
      children or adolescents, a treatment of their class II malocclusion that is not
      only effective but also the most appropriate for each individual case? Which
      schedule and what therapeutic device should be used? MATERIALS AND METHODS:
      Evidence-based orthodontics, along with a search for the best data on two-phase
      treatments, were used to judge the validity of the main objectives sought when
      correcting a Class II malocclusion in children or adolescents, including
      treatment of mandibular retrognathy. RESULTS: Published data show that the long
      term effects of a first phase of treatment on the amount of mandibular growth are
      at best weak and clinically insignificant. This observation triggers a paradigm
      shift by refocusing patient treatment on the achievement of other therapeutic
      objectives. A new orthodontic appliance, the Clas II Corrector, is presented. Its
      advantages and its use are described and illustrated by means of clinical cases.
      CONCLUSIONS: Class II Corrector allows distalization of maxillary lateral areas,
      effectively limits undesirable dentoalveolar compensations and facilitates the
      rehabilitation of orofacial functions. In addition to its clinical efficacy,
      patients appreciate its small footprint, ease of wearing, and lack of impact on
      phonation.

PMID- 29043967
TI  - Dual head screw hip nailing for trochanteric fractures.
AB  - INTRODUCTION: There are limited information and inconclusive results for dual
      head screw intramedullary hip nails for trochanteric fractures. Therefore, we
      performed a prospective study to evaluate the healing of fractures, and survival,
      function, and complications of patients operated with this implant. METHODS: We
      prospectively studied 79 patients (61 women and 18 men; mean age: 84.7 years;
      range: 65-96 years) with a low-energy trochanteric fracture, treated with a dual
      head screw intramedullary hip nail from 2013 to 2016. The mean follow-up was 2.1
      years (range: 1-3 years); seven patients were lost to follow up. This left 72
      patients for further analysis. We evaluated the healing of fractures, and
      survival, function, and complications of patients. RESULTS: Fracture healing was
      evident in 70 patients (97.2%) at 2-3 months postoperatively. One patient
      experienced cut-out and z-effect phenomenon of the head screws. Another patient
      experienced a periprosthetic femoral diaphysis fracture at the distal tip of the
      nail. A third patient experienced an acute postoperative superficial skin
      infection that was treated successfully with wound dressing changes and a course
      of antibiotics. Sixteen patients (22.2%) deceased within 12 months
      postoperatively. In the remaining patients, the Harris Hip Score (HHS) at 12
      months postoperatively was excellent in 16 (28.6%), good in 23 (41.1%), fair in
      10 (17.8%), and poor in 7 patients (12.5%). The function declined after the
      patients' fracture. Fair and poor results were related to age > 85 years, poor
      pre-fracture level of function, and AO/OTA-31-A3 fracture types. CONCLUSION: The
      dual head screw intramedullary hip nail is associated with high healing and low
      complication rates for intertrochanteric fractures. The function of the patients
      is good or excellent in most cases; however, it declines, especially for those
      patients with age > 85 years, poor pre-fracture level of function, and AO/OTA-31
      A3 fracture types.

PMID- 29043971
TI  - [What are the treatment needs in adults? An evaluation of 258 cases by the IOTN].
AB  - INTRODUCTION: The aim of this epidemiological study was to evaluate the need for
      orthodontic treatment in a sample of adults living in France. MATERIALS AND
      METHODS: The indicator selected was the dental component, IOTN (index of
      orthodontic treatment need). RESULTS: Among the 258 adults evaluated, 37% of
      patients had a strong need and 21% had a moderate need; 29% of those aged 35 and
      under were in strong need for treatment compared with 47% of those over 35 years,
      with the need for treatment increasing with age. The most frequent occlusal
      anomalies were dental migrations following an uncompensated tooth extraction (a
      situation that involved 22% of subjects). It was the only occlusal anomaly whose
      frequency increased significantly with age. Among patients with uncompensated
      tooth extraction, two thirds experienced dental migrations requiring orthodontic
      treatment. DISCUSSION: Although the IOTN indicator is widely used in the
      literature, it is controversial since all the characteristics evaluated are
      liable to impact longevity and the functioning and esthetics of the dentition,
      thus excluding any other consideration. The need for treatment in adults in
      France would therefore appear to be greater than in adolescents and would seem to
      increase with age, mainly due to uncompensated dental extractions.

PMID- 29043972
TI  - [Effects of maxillary disjunction on canine impaction in patients presenting a
      maxillary transverse skeletal deficiency].
AB  - INTRODUCTION: This study focuses on the effects of rapid maxillary disjunction on
      the tendency to canine impaction in patients displaying a maxillary transverse
      skeletal deficiency. MATERIALS AND METHODS: Using the segmentation method
      described by Ericson and Kurol and modified by Lindauer, et al., a series of
      panoramic views taken before and after disjunction was studied to compare changes
      in the position of the tip of the maxillary canine depending on whether it was
      covered or not by the homolateral lateral incisor, according to the side and
      patient's sex. The cohort consisted of 193 patients, all treated using a palatal
      expander welded to bands. RESULTS: A statistically significant improvement was
      observed in all categories regarding the position of the maxillary canine.
      Disjunction was successful in 87% of cases in our sample. No significant
      differences were found according to side or sex.

PMID- 29043973
TI  - [Aesthetic perception of the vertical position of the incisal edges of the
      maxillary lateral incisors in the smile arch].
AB  - INTRODUCTION: The aim of this study is to assess the attractiveness in the smile
      arch of different vertical positions of the incisal edges of the maxillary
      lateral incisors. MATERIAL AND METHODS: A frontal photograph of a Caucasian
      woman's smile was digitally modified to obtain an image with the incisal edges of
      the maxillary lateral incisors symmetrically tangent to the smile arch. These
      incisal edges were then moved vertically by 0.5 mm increments. The value was
      considered positive for an occlusal shift and negative for a gingival shift. Four
      other images were obtained by moving the incisal edges from +0.5 mm to -1.5 mm.
      The five images were rated on a visual analog scale by three groups of
      evaluators: orthodontists, dentists and laypersons. A statistical analysis was
      performed. RESULTS: Laypersons preferred first lateral incisors tangent to the
      smile arch, second a +0.5 mm shift, and third a -0.5 mm shift. Orthodontists and
      dentists preferred first a -0.5 mm shift and second a null shift. CONCLUSIONS:
      The aesthetic perception of the smile, as regard to the vertical relationships
      between the incisal edges of the anterior teeth, differs between laypersons and
      professionals but remains homogenous between orthodontists and dentists. The most
      consensual aesthetic situation, from both professionals' and laypersons' points
      of view, is the geometry in which the incisal edges of the maxillary lateral
      incisors are tangent to the smile arch.

PMID- 29043974
TI  - [What are the cephalometric features of "good" and "bad" guys in cartoons?]
AB  - OBJECTIVE: The objective of the study was to search for links between specific
      facial features and the psychology of the "good" and "bad" guys in cartoons.
      MATERIAL AND METHOD: We made 60 cephalometric tracings and compared the
      characters' profiles using statistical tests. RESULTS: The "bad guy" profile is
      closer to the normal profile of real humans than that of the "good guys".
      Profiles perceived as "good" in cartoons appear to be stereotyped. Thus, any
      profile not matching the "norm" can be interpreted as being unpleasant and
      consequently associated with the features of the "bad guys". The standard "bad
      guy" profile has a longer more prominent nose, a jutting chin (a bigger soft
      tissue angle) and a higher upper third of the face than the lower third (the
      opposite of the standard profile of the "good guys"). DISCUSSION: These
      standardized portraits reflect and influence the (subconscious) prejudices of
      both young and less young movie-goers (not to mention the cartoonists) regarding
      their fellow humans.

PMID- 29043975
TI  - [Preventive and therapeutic advantages of sugar-free chewing gums in
      orthodontics. A study conducted on practitioners and patients].
AB  - OBJECTIVE: The objective of this study is to assess the level of knowledge in a
      cohort of oral health professionals and patients about preventive and therapeutic
      actions of sugar-free chewing gums. MATERIALS AND METHODS: A forward-looking
      monocentric study of perception regarding the level of information about the
      effects of sugar-free chewing gums consumption was conducted on 135 young
      patients, from 11 to 17 years old, carriers of fixed orthodontic appliances and
      treated in the Department of Orthodontics in the Oral Medicine and Surgery Center
      of the University Hospitals of Strasbourg. Besides, 34 practitioners in the
      Department of Orthodontics and Pediatric Dentistry were also included. Data were
      collected between May 2016 and July 2016. A specific questionnaire, using the
      adapted terminology and dealing with the same items was developed for each
      studied population. RESULTS: The majority of the individuals of both studied
      populations believe that the consumption of sugar-free chewing gum leads to a
      greater risk of orthodontic device unsticking or fracture and that it is not
      associated to a decrease of the orthodontic pain. DISCUSSION: Our results confirm
      the fact that the knowledge, mainly acquired in an empirical way, is against the
      data of the current literature. The evaluation of the level of knowledge
      demonstrated that there is a real lack of information about the preventive
      interests of the consumption of sugar-free chewing gums during orthodontic
      treatment. CONCLUSIONS: This study highlights the need for information campaigns
      and oral prevention in general population, as well as in healthcare
      professionals, concerning the preventive and analgesic interests of sugar-free
      chewing gums during orthodontic treatments.

PMID- 29043976
TI  - ?

PMID- 29043977
TI  - A protein phosphatase network controls the temporal and spatial dynamics of
      differentiation commitment in human epidermis.
AB  - Epidermal homeostasis depends on a balance between stem cell renewal and terminal
      differentiation. The transition between the two cell states, termed commitment,
      is poorly understood. Here, we characterise commitment by integrating
      transcriptomic and proteomic data from disaggregated primary human keratinocytes
      held in suspension to induce differentiation. Cell detachment induces several
      protein phosphatases, five of which - DUSP6, PPTC7, PTPN1, PTPN13 and PPP3CA -
      promote differentiation by negatively regulating ERK MAPK and positively
      regulating AP1 transcription factors. Conversely, DUSP10 expression antagonises
      commitment. The phosphatases form a dynamic network of transient positive and
      negative interactions that change over time, with DUSP6 predominating at
      commitment. Boolean network modelling identifies a mandatory switch between two
      stable states (stem and differentiated) via an unstable (committed) state.
      Phosphatase expression is also spatially regulated in vivo and in vitro. We
      conclude that an auto-regulatory phosphatase network maintains epidermal
      homeostasis by controlling the onset and duration of commitment.

PMID- 29043979
TI  - Warm, Cozy Woodstoves . . .  and the PM They Produce: Home Interventions Show
      Mixed Results in Protecting Children with Asthma.

PMID- 29043980
TI  - A support to biological validation of oxygenation parameters.
AB  - Blood gas analyzers are able to provide information on a wide range of
      oxygenation parameters. Some of these data are complex. Their biological
      significance or clinical consistency are not always well known. This article aims
      to define these parameters, their reference values according to the type of
      sample; and to outline the possible errors during their interpretation. Thus,
      these reliable results can be integrated into the diagnostic procedure. We will
      see that the information provided by physicians plays an important role in their
      interpretation (temperature, patient ventilation condition, type of sample...).
      Knowing the physiological significance of complex data such as the oxygen
      alveolar-arterial gradient, or the estimated fraction of shunt, as well as the
      factors influencing them, allows us to improve their biological validation as
      accurately as possible. Finally, we will summarize the major oxygenation
      disorders and their impact on the results of blood gas analysis.

PMID- 29043978
TI  - A unified internal model theory to resolve the paradox of active versus passive
      self-motion sensation.
AB  - Brainstem and cerebellar neurons implement an internal model to accurately
      estimate self-motion during externally generated ('passive') movements. However,
      these neurons show reduced responses during self-generated ('active') movements,
      indicating that predicted sensory consequences of motor commands cancel sensory
      signals. Remarkably, the computational processes underlying sensory prediction
      during active motion and their relationship to internal model computations during
      passive movements remain unknown. We construct a Kalman filter that incorporates
      motor commands into a previously established model of optimal passive self-motion
      estimation. The simulated sensory error and feedback signals match experimentally
      measured neuronal responses during active and passive head and trunk rotations
      and translations. We conclude that a single sensory internal model can combine
      motor commands with vestibular and proprioceptive signals optimally. Thus,
      although neurons carrying sensory prediction error or feedback signals show
      attenuated modulation, the sensory cues and internal model are both engaged and
      critically important for accurate self-motion estimation during active head
      movements.

PMID- 29043981
TI  - Southeast asian ovalocytosis: the need for a carefull observation of red cell
      indices and blood smear.
AB  - Southeast asian ovalocytosis (SAO) is characterized by macro-ovalocytes and ovalo
      stomatocytes on blood smear. SAO is common in Malaisia and Papua-New-Guinea where
      upwards to 40 per cent of the population is affected in some coastal region.
      Inherited in an autosomal dominant way, illness results from deletion of codons
      400-408 in SLC4A1 gene which encodes for band 3 erythrocyte membrane protein.
      This deletion is responsible for an unusual erythrocyte stiffness and oval shape
      of the cells on blood smear. Heterozygous carriers are usually asymptomatic
      whereas homozygous are not viable without an intensive antenatal care. Here, we
      describe 4 patients diagnosed incidentally by cytogram appearance of the Advia(r)
      2120i (Siemens) representing hemoglobin concentration according to red blood mean
      cellular volume (GR/VCH).

PMID- 29043983
TI  - Trisomy 13 by robertsonian translocation rob (13;13)(q10;q10) +13: about one
      case.
AB  - We are reporting a rare case of foetal trisomy 13 due to a robertsnonian
      translocation. Further to the study of both parents karyotypes, genetic
      councelling is advisable in order to assess the potential risk of trisomy that
      may occur during a future pregnancy.

PMID- 29043982
TI  - Preanalytical influence of pneumatic tube delivery system on results of routine
      biochemistry and haematology analysis.
AB  - Pneumatic tube delivery system (PTS) enables to reduce considerably turnaround
      times. The aim of the study was to assess the influence of the PTS on the quality
      of routine biochemical and hematological tests in our laboratory. Blood samples
      from 6 hospitalized patients and 8 healthy volunteers were analyzed. Blood
      samples were delivered to the laboratory by a PTS and by a human courier. We
      performed the following analysis: ionized calcium, sodium, potassium, lactate
      deshydrogenase (LDH), aspartate aminotransferase (ASAT), arterial blood gas,
      complete blood count and coagulation test as prothrombin time, activated partial
      thromboplastin time, factors V and VIII. Results were compared between the both
      method of transport according to the recommendation of the Societe francaise de
      biologie clinique and the French committee for accreditation (SH-GTA01, norme NF
      ISO 5275-6). The hemolysis index of plasma was similar between the groups and no
      morphological differences were found on blood cells. For three samples, when
      delivered by PTS, LDH levels (two samples) and neutrophil polynuclear count (one
      sample) were above the recommended guidelines compared to those delivered by
      courier. Conversely, LDH levels and FVIII were below in two samples delivered by
      PTS. LDH levels, PNN count or factor VIII can be affected by PTS without the
      clinical interpretation being modified. We concluded that the PTS can be used to
      transport blood samples for routine biochemical and hematological analysis in our
      hospital.

PMID- 29043984
TI  - Optimization of pre-analytical conditions for measurement of biomarkers in
      seminal plasma: application to adipokines.

PMID- 29043985
TI  - From the observation of atypical cells on blood smear to the diagnosis of mast
      cell leukemia: a case report in a 79 year old woman consulting for anemia.
AB  - Mast cell leukemia is an extremely rare disease, which belongs to the systemic
      mastocytosis group (WHO 2016). We are reporting the case of a 79-year-old woman,
      without any hematological particular history consulting for hyperthermia,
      repeated malaise and subacute anemia. Her clinical examination was normal.
      Unusual cells were seen on blood and bone marrow smears. They represent more than
      10% of blood nucleated cells end more than 20% of the bone marrow nucleated
      cells. Bone marrow immunophenotyping was performed to characterize these cells.
      It revealed a cell subset expressing the surface antigens CD117, CD2 and CD25.
      This immunophenotypic profile is the hallmark of malignant mast cells. Then mast
      cell leukemia diagnosis could have been made and KIT gene sequencing highlighted
      the N822Y mutation in exon 17. The patient was initially treated with
      midostaurin, a tyrosine kinase inhibitor. Lack of therapeutic response and
      absence of the KIT D816V mutation led to switch to imatinib, following the latest
      scientific recommendations.

PMID- 29043986
TI  - Potential of big data analytics in the French in vitro diagnostics market.
AB  - The new paradigm of the big data raises many expectations, particularly in the
      field of health. Curiously, even though medical biology laboratories generate a
      great amount of data, the opportunities offered by this new field are poorly
      documented. For better understanding the clinical context of chronical disease
      follow-up, for leveraging preventive and/or personalized medicine, the
      contribution of big data analytics seems very promising. It is within this
      framework that we have explored to use data of a Breton group of laboratories of
      medical biology to analyze the possible contributions of their exploitation in
      the improvement of the clinical practices and to anticipate the evolution of
      pathologies for the benefit of patients. We report here three practical
      applications derived from routine laboratory data from a period of 5 years
      (February 2010-August 2015): follow-up of patients treated with AVK according to
      the recommendations of the High authority of health (HAS), use of the new
      troponin markers HS and NT-proBNP in cardiology. While the risks and difficulties
      of using algorithms in the health domain should not be underestimated - quality,
      accessibility, and protection of personal data in particular - these first
      results show that use of tools and technologies of the big data repository could
      provide decisive support for the concept of "evidence based medicine".

PMID- 29043987
TI  - Successful treatment of donor cell derived myelodysplastic syndrome with 5
      azacytidine.

PMID- 29043988
TI  - Effects of estrogen on learning-memory and expression of calbindin-D28K in
      hippocampus in vascular dementia rats.
AB  - Vascular dementia (VD) models were made first by repeating cerebral ischemia
      reperfusion and followed by treating with estrogen. Learning-memory ability was
      measured by Morris water maze. Concentration of Ca2+ in hippocampus was
      determined by Fura-2/AM fluorescence probe and the expression of Calbindin-D28K
      (CB) in hippocampal CA1 was tested by immunohistochemistry. Learning-memory
      ability was improved in E group rats; Concentration of Ca2+ in hippocampus was
      decreased in E group rats. The expression of CB was less in E group rats. It
      implies that estrogen could improve learning-memory ability in VD rats, which may
      be associated with suppressing intracellular Ca2+ overload and increasing the
      expression of CB in hippocampus.

PMID- 29043989
TI  - Antiviral screening of four plant extracts against acyclovir resistant herpes
      simplex virus type-1.
AB  - Herpes simplex virus type 1 (HSV-1) causes serious infections particularly in
      immunocompromised patients. Methanolic extract of four plants were evaluated for
      their anti-viral effects against acyclovir resistant HSV-1 in HeLa cell line. The
      50% cytotoxic concentration (CC50) as well as the effective minimal cytotoxic
      concentration of each plant extract were evaluated by MTT assay. Antiviral
      effects of the plant extracts on HSV-1 were examined at different concentrations
      of the extract. The effective minimal cytotoxic concentration was evaluated at
      different times of virus replication after infection. Virus titration was
      assessed by tissue culture infectious dose 50 (TCID50) method. Among the 4 plant
      extracts evaluated only Mentha pulegium L. extract was shown to exert the highest
      antiviral activity, with selectivity index (SI) 10.25. Direct treatment of HSV-1
      with Mentha pulegium L. extract resulted in 1.7 log10 TCID50 reduction in virus
      titers after one hour. The highest reduction in HSV-1 infectivity was obtained 1
      hour after the infection of the cells with virus resulting in 2.1 log10 TCID50
      reduction as compared to the control. The antiviral effects of Mentha pulegium L.
      extract on HSV-1 after virus infection was more remarkable than the virucidal
      activity.

PMID- 29043990
TI  - Tumor necrosis factor-alpha and procalcitonin level variations in the serum and
      their effects on organ function in patients with severe acute pancreatitis during
      infected stage.
AB  - To investigate the changes of tumor necrosis factor-alpha (TNF-alpha) and
      procalcitonin (PCT) in the serum and their effects on organ function in patients
      with severe acute pancreatitis (SAP) during infected stage, aiming to provide a
      reference to individual treatment. 32 patients with SAP during infected stage
      admitted to the Digestive Department of The Second Affiliated Hospital of
      Zhengzhou University from April 2014 to May 2015 and also 30 volunteer normal
      people were recruited in this study. And 26 patients detected with positive
      pathogenic bacteria were grouped into group A and another 6 patients with
      negative pathogenic bacteria into group B and 30 normal people into group C. And
      TNF-alpha and PCT level in the serum and the liver, kidney and lung function and
      the relationship between them of all the included people were compared and
      analyzed. the serum TNF-alpha level detected in the bile, urine and the surface
      of wound in group A was much higher than that in group B (P<0.05); and there was
      no significant difference in PCT between group A and group B; and TNF-alpha and
      PCT level in the serum in group A and group B were remarkably higher than group C
      (P<0.05). In addition, the organ function (the liver, kidney and lung) in the
      patients with high TNF-alpha level (High TNF-alpha group) was significantly
      different from the patients with low TNF-alpha level (Low TNF-alpha group)
      (P<0.05). And various organ functional indexes increased significantly in the
      patients with high PCT level (P<0.05). There were two kinds of TNF-alpha level
      (high level and low level) in the patients during SAP general infection stage,
      and the high level may reduce various organ function, the low level can
      contribute to the regular inflammatory response. And there is a high PCT level in
      the early SAP infection stage, which can be used to predict the patients'
      condition.

PMID- 29043991
TI  - Correlation between antioxidant activity and phenolic acids profile and content
      of Algerian propolis: Influence of solvent.
AB  - We aimed in the reported study to investigate the impact of using various
      solvents in the extraction of potentially active compounds from Algerian
      propolis. Phenolic and flavonoids contents in association with antioxidant
      activity of the tested extracts were evaluated. Moreover phenolic composition was
      determined using UFLC-MS/MS. The tested parameters varied according to the used
      solvent. Total phenolic and flavononid contents ranged from 0.81+/-0.16 to 8.97+/
      0.25 EGA mg/g and from 0.57+/-0.01 to 3.53+/-0.84 EQ mg/g respectively. All the
      investigated extracts demonstrated notable antiradical and reducing activities.
      Ethyl acetate and n-butanol were found to contain the highest amounts of phenolic
      and flavonoid compounds and the strongest antioxidant properties. The antioxidant
      activity of propolis extracts appears to be largely influenced by total phenolic
      and flavonoid contents. Rutin, chlorogenic, ferulic, caffeic and gallic acids
      were found to be the main phenolic compounds in Algerian propolis. Our results
      suggest that Algerian propolis may be a poplar-type propolis.

PMID- 29043992
TI  - Correlation of the ultrasound imaging of breast cancer and the expression of
      molecular biological indexes.
AB  - This paper aims to 137 cases of breast malignant tumors confirmed by surgery and
      pathology were collected. All patients received ultrasound examination and were
      not treated by radiotherapy or chemotherapy before operation. The preoperative
      ultrasound images of breast cancer patients and postoperative pathological
      characteristics of paraffin sections were retrospectively observed. Ultrasound
      indicators included tumor size, shape, ratio of the longest/shortest dimension,
      edge of the spiculation and peripheral hyperechoic halo sign, internal echo
      types, micro calcification, posterior echo types, blood flow and signs of lymph
      node metastasis. The pathological indexes included histological type,
      infiltrating ductal carcinoma (IDC), histological grading, cancer tissue in the
      interior and edge of the lesion and stroma and expression of molecular biology
      indexes (ER, PR and C-erbB-2). The correlation of ultrasound imaging of breast
      cancer and his to pathological type and grading were analyzed and the ultrasounic
      characteristics and the his to pathological features was compared; then to
      explore the correlation of ultrasonic imaging of breast cancer and the expression
      of ER, PR and C-erbB-2. the tumor size of IDC (>2cm) was lager than that of the
      ductal carcinoma in situ (DCIS) and the early-stage IDC, with statistical
      significance (P<0.05), but compared with the specific carcinoma of breast
      (P>0.05). The ratio of irregular mass of IDC was more than that of the specific
      carcinoma of breast (P<0.05), but without statistical significance compared with
      the DCIS and early-stage IDC (P>0.05). The spiculate margin in the IDC was more
      than that of the early-stage IDC, DCIS and specific carcinoma of breast (P>0.05).
      The ratio of the longest/ shortest dimension, peripheral hyperechoic halo sign,
      internal echo, micro calfication, posterior echo types were not related to the
      types of breast cancer (P>0.05). The irregular mass rate in the III IDC were much
      higher than that in the I and II level IDC (P>0.05). The posterior echo
      attenuation in the I IDC was much higher than the II and III IDC (P>0.05). The
      tumor size, spiculate margin, peripheral hyperechoic halo, internal echo types,
      micro calcification were not significantly related to the histological grading of
      IDC. The tumor with larger size (>2cm), enhanced posterior echo, or lower
      internal echo will have a high histological classification and high rate of
      cancer tissue (P<0.05). The tumor with enhanced peripheral hyperechoic halo sign
      will have a higher histological classification and higher rate of cancer tissue
      in the peripheral tissues, compared with the tumors without halo (P<0.05). The
      tumor shape, ratio of the longest/ shortest dimension, spiculate margin were not
      significantly related to the internal tissues (P>0.05). The ratio of the longest/
      shortest dimension (>1), spiculate margin and halo signs were related to the
      positive expression of ER and PR (P<0.05). The internal necrosis was related to
      the negative expression of PR, (P<0.05). The tumor size, shape, posterior echo
      types and blood flow were not significantly related to the expression of ER, PR
      and C-erbB-2 (P>0.05).

PMID- 29043993
TI  - Serum levels of leptin, zinc and tryptophan in obese subjects with sleep
      deficits.
AB  - Obesity is an important risk factor for sleep disorders. This study aimed to
      evaluate the association of leptin, zinc and tryptophan (TRP) in obese subjects
      with sleep deficits [sleep apnea (SA), insomnia (IN)]. In this cross sectional
      case control, with the verbal and written consent 206, obese with sleep deficits
      and 30, non-obese/normal identified from various areas of Karachi, Pakistan. The
      socio-demographic data including; age, body mass index (BMI), education and
      residence, of participants was collected. After providing informed consent,
      fasting blood samples were taken and serum was collected. The serum concentration
      of leptin, zinc and TRP were analyzed by ELISA (Enzyme-linked immunosorbent
      assay), FAAS (Flame atomic absorption spectrophotometer) and HPLC (High
      performance liquid chromatography) respectively. A significant correlation was
      found between BMI (body mass index) and leptin, BMI and zinc, BMI and TRP. The
      correlation between leptin consecutively was significantly associated with zinc
      and TRP in obese patients. Sleep deficits elevated circulatory levels of leptin
      while lower zinc and TRP levels compared to levels seen in non-obese (Normal)
      subjects with no sleep deficits. Obese subjects exhibited significantly higher
      levels of leptin with sleep deficits compared with non-obese subjects with normal
      sleep pattern, while obese subjects with SA had significantly high levels of
      leptin than obese subjects with IN and IN+SA. Patients with sleep deficits had
      significantly lower levels of serum TRP and zinc than non-obese subjects with
      normal sleep pattern. Obese subjects with SA had significantly lower levels of
      zinc and elevated levels of TRP than obese subjects with IN. Obese patients with
      IN+SA had significantly lower levels of leptin and zinc than IN and SA , while
      TRP levels were significantly lower in subjects with IN than obese subjects with
      IN+SA and IN. These results suggest that elevated levels of leptin which are
      possibly by adiposity and lessened levels of zinc and TRP have a great impact on
      progression of obesity and their association can contribute to tempt sleep
      disorders.

PMID- 29043994
TI  - Terpenic profile of different Rosmarinus officinalis extracts.
AB  - The Rosemary (Rosmarinus officinalis L.), a well-known medicinal and culinary
      herb, was studied to compare the terpenic profile of different extracts obtained
      from dry and fresh herb. There were studied the volatile oil extracted by hydro
      distillation from dry plant, the hydroalcoholic extracts obtained from fresh
      respectively dry plant and the glycerol macerate obtained from fresh plant, by GC
      MS using headspace injection. The separated compounds were identified using a MS
      spectra library. The quantitative determination was performed by normalization
      respectively by calibration curve method for 1,8-cineole, alpha-pinene and D
      limonene. The main separated compounds were alpha-pinene, 1,8-cineol, camphene,
      camphor, D-limonene and cymene. A significant difference was observed between the
      4 samples volatile profiles. 1,8-cineole was found major component of the
      essential oil (VO-21.39%) and glycerol macerate (GM-35.60%), while and alpha
      pinene was detected as the main constituent of the two tinctures (T-46.05%; MT
      31.93%). The highest 1,8-cineol content, determined by calibration curve method,
      was found in the volatile oil, while the fresh plant hydroalcoholic extract was
      richer in alpha-pinene and D-limonene.

PMID- 29043995
TI  - Clinical research of homocysteine, high-sensitive C-reactive protein and D-Dimer
      in patients with vascular dementia.
AB  - Aim of the present research work was to study the relationship between the degree
      of dementia and the serum levels of homocysteine(Hcy), high-sensitive C-reactive
      protein(hs-CRP), D-Dimer and vascular dementia(VaD) of patients, and to
      investigate the mechanism of Hcy, hs-CRP and D-Dimer in the vascular dementia.
      Subjects were divided into normal group and VaD group. CRP and D-Dimer protein of
      each sample were detected by nephelometry method, and the serum Hcy level was
      detected by Fluorescent labeling immunoassay method. Compared with the normal
      control group, Hcy, hs-CRP and D-Dimer in VaD group were significantly higher
      than that of control group, and the difference was statistically significant.
      Linear correlation analysis showed a negative association between Hs-CRP, Hcy and
      MMSE score. There was no correlation between the levels of D-Dimer and the MMSE
      score. Hcy, hs-CRP and D-Dimer are involved in the pathogenesis of vascular
      dementia (VAD), There is a significant correlation between the severity of
      vascular dementia and Hcy and Hs-CRP.

PMID- 29043996
TI  - Clinical therapeutic strategy of recombinant human brain natriuretic peptide and
      dopamine in cardiorenal syndrome type 4 patients combined with hypotension.
AB  - Aim of the present study is to investigate the clinical efficacy of recombinant
      human brain natriuretic peptide (rhBNP) and dopamine combination treatment in
      patients with cardiorenal syndrome type 4 (CRS4) combined with hypotension. A
      total of 160 CRS4 patients admitted to our hospital from July 2010 to December
      2014 were recruited, and were randomly divided into two groups, the observational
      group (n=80) and the control group (n=80). CRS4 patients treated with dopamine
      were recruited into the control group. Patients in the observational group were
      given rhBNP and dopamine combination treatment once every 8 h. Both groups
      received conventional treatments and the course of treatment was 7 days. Systolic
      blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure
      (MAP), heart rate (HR), serum creatinine (SCr), N-terminal brain natriuretic
      peptide precursor (Nt-proBNP), creatinine clearance (CCr), left ventricular end
      diastolic diameter (LVEDd), left ventricular ejection fraction (LVEF), Stroke
      volume (SV), urine volume and adverse reactions before and after treatment were
      compared. The observational group showed significant changes in the levels of
      SBP, DBP and HR compared with the control group (P<0.05). The levels of SCr and
      Nt-proBNP decreased significantly in the observational group than those in the
      control group (P<0.05). The levels of CCr, LVEF, SV and urine volume increased
      significantly in the observational group than those in the control group
      (P<0.05). Patients in the observational group had mild and tolerable adverse
      reactions. rhBNP combined with dopamine infusion has good clinical efficacy and
      mild adverse effects in treatment of CRS4.

PMID- 29043997
TI  - Correlation between compliance in patients with anti-hypertensive therapy and
      blood pressure control.
AB  - This paper aims to understand the blood pressure control status for hypertension
      patients, and discuss the relationship between social support, medication
      compliance and blood pressure for hypertensive patients. The survey objective was
      the hypertensive patients in chronic disease management system in Xinxiang city.
      The survey was conducted as the questionnaire survey filled by objectives. Social
      support rating scale and medication therapy compliance questionnaire was utilized
      to evaluate the patients' social support and medication therapy compliance. 1095
      patients in medication were investigated, the blood pressure of 66.6%
      investigated objectives was controlled at target levels (<140/90 mmHg), 70.0%
      investigated objectives have good medication therapy compliance; the overall
      social support score for hypertensive patients in medication was (40.01+/-6.54)
      points, the subjective support score, objective support score and support
      utilization degree score were respectively (24.43+/-4.61) points, (8.59+/-2.59)
      points and (7.00+/-2.06) points; Rank correlation coefficient of Spearman
      illustrated that the support utilization rating evaluation was apparently
      correlated to medication therapy compliance (rs=0.88, P<0.01); multivariate
      analysis proved that the protective factors for medication therapy compliance
      were the high support utilization rate (OR 1.62; 95%CI 1.19~2.05), long
      hypertensive duration (5~10 years: OR 2.01, 95%CI 1.42~2.73; more than 10 years:
      OR 1.46, 95%CI 1.01~1.99) and high average monthly household income (OR 2.03,
      95%CI 1.45~2.69); Risk factor for blood pressure control were male (OR 0.61, 95%
      CI 0.47~0.79) and high hypertensive grade (OR 0.31, 95%CI 0.19~0.44); The
      protective factors for blood pressure control was good medication therapy
      compliance (OR 1.54, 95%CI 1.22~1.89), (average P<0.05). It required to build
      effective social support system, increase patients' social support utilization
      degree, emphasized the intervention on low average monthly household incomes,
      male higher rate, higher hypertensive degree, and further improve the medication
      therapy compliance and hypertensive control rate of hypertensive patients.

PMID- 29043998
TI  - Clinical study of water drinking test and 24-hour intraocular pressure monitoring
      in patients with primary open angle glaucoma.
AB  - This paper aims to observe the relevance of 24-hour intraocular pressure (IOP)
      monitoring and water drinking test (WDT) in patient with primary open angle
      glaucoma (POAG). 55 patients (90 eyes) with POAG was selected and randomly
      divided into operation group and drug group. Operation group, with 30 cases (48
      eyes), were treat with trabeculectomy. And the other 25 cases (42 eyes) were
      treated with antiglaucoma medication. 24-hour intraocular pressure and WDT were
      measured before treatment and 6 months after treatment. The correlation between
      the peak value of 24-hour intraocular pressure (IOP) and intraocular pressure
      (IOP) fluctuation and the drinking water test were analyzed. Pearson correlation
      analysis showed a strong positive correlation between the peak value of diurnal
      IOP and the peak value of WDT IOP (r=0.758); and the Pearson correlation analysis
      also showed a strong positive correlation between the peak value of diurnal IOP
      and the peak value of WDT IOP after 6 months of POAG surgery or drug therapy
      (r=0.759,0.712). The peak value of IOP and IOP fluctuation in operation group
      were lower than those in the drug group at 6 months after operation, the
      difference was statistically significant. The peak value of WDT IOP can reflect
      the curve peak value of 24-hour IOP, which can be used to evaluate the current
      treatment. There were significant differences in IOP and IOP fluctuation between
      the drug group and the operation group at 6 months after treatment. Operation
      groups could achieve lower IOP and IOP fluctuation.

PMID- 29043999
TI  - Study of global DNA methylation in monozygotic twins with cerebral palsy.
AB  - The objective of this paper is to study the global DNA Methylation in monozygotic
      (MZ) twins with cerebral palsy. Two pairs of twins (a cerebral palsy children, a
      normal child) admitted to the First Affiliated Hospital of Zhengzhou University
      were selected as subjects. The phenol-chloroform method was used to extract DNA
      from venous blood and micro satellite DNA genotyping technique was used to
      identify the eggs of the twins. DNA methylation fragments were enriched by MBD
      affinity column chromatography, followed by Solexa sequencing and bioinformatics
      analysis. In this study, we found that there were different DNA hypermethylation
      regions between each pair of twins and normal children through global DNA
      methylation analysis technique by analyzing the blood cells of two pairs of
      monozygotic twins with cerebral palsy and normal infants. The results revealed
      the region of DNA methylation and the protein coding genes of promoter region of
      common methylation of cerebral palsy were both higher than normal children. These
      common promoter hypermethylation genes in cerebral palsy are involved in a
      variety of biological processes such as membrane protein transport, neuronal
      development, apoptosis, and metabolism. Moreover, DNA methylation plays an
      important role in gene expression. We hypothesized that the onset of cerebral
      palsy in twins is associated with hypermethylation of the promoter which
      inhibiting the expression of hypermethylation genes in children with cerebral
      palsy. The current research provided a basis for further study of the large
      sample of twins and sporadic cerebral palsy.

PMID- 29044000
TI  - Observation on Shenqi Fuzheng injection combined with cefoxitin sodium after
      cesarean section.
AB  - This paper aims to observe the effect of Shenqi Fuzheng Injection combined with
      cefoxitin sodium after cesarean section. Clinical data of 126 puerperae were
      retrospectively analyzed. They randomized into control group and treatment group,
      and there were 63 cases in each group. Patients in control group were given
      Cefoxitin Sodium treatment. And patients in treatment group were given Shenqi
      Fuzheng Injection on the basis of control group. After 7 days of treatment, the
      clinical curative effect of the two groups was observed and compared. The body
      temperature of the patients in treatment group was significantly decreased when
      compared with control group on the 2nd and 3rd day after operation (P<0.05); the
      first exhaust time and defecation time of patients in treatment group were
      significantly shortened when compared with control group (P<0.05); the
      postoperative hemoglobin and red blood cell count in both groups were all
      significantly increased when compared with before treatment (P<0.05), and the
      treatment group were evidently higher than control group (P<0.05); the
      postoperative neutrophilic granulocyte percentage, white blood cell count and
      lymphocytes percentage in both groups were all significantly lowered when
      compared with before treatment (P<0.05), and the neutrophilic granulocyte
      percentage, white blood cell count and lymphocytes percentage in treatment group
      were significantly lowered when compared with control group (P<0.05). Shenqi
      Fuzheng injection combined with cefoxitin sodium after cesarean section can
      effectively reduce the postoperative maternal body temperature and promote the
      recovery of maternal gastrointestinal function, which is conducive to the repair
      of uterus, further correct anemia after cesarean section and prevent postpartum
      infection. Its clinical curative effect is ideal, with certain clinical
      application value.

PMID- 29044001
TI  - Vitrectomy combined with intracular drug injection on treatment of
      endophthalmitis.
AB  - This paper aimed to evaluate the clinical application value of vitrectomy
      combined with intraocular drug injection on treatment of severe endophthalmitis.
      Retrospective analyzed the 28 eyes for the 28 cases of patients suffering severe
      endophthalmitis, and with treatment of pars plana vitrectomy combined with
      intraocular drug injection, and foreign matter removal surgery. This study also
      analyzed the whole body and local application of antibiotics data, and clinical
      data of corticosteroid drug treatment. This study had followed up 6 to 12 months,
      28 intraocular infected eyes of the 28 cases all had got controlled. The vision
      of 26 eyes improved to some degree, 2 eyes had eyeball atrophy. vitrectomy
      combined with intraocular drug injection was the most effective method to
      treatment the suppurative endophthalmitis.

PMID- 29044002
TI  - Irrational antibiotic prescribing practice among children in critical care of
      tertiary hospitals.
AB  - This study assessed the prescribing pattern of irrational use of antibiotic among
      children under age of 12 years in public and private sector hospitals in
      Pakistan. The prospective clinical evaluation of drug utilization pattern of
      antimicrobials from Patient Bedside File (PBF) of in-patients and Culture
      Sensitivity Test (CST) reports were evaluated to determine the antibiotic
      resistance. Two indicators recorded to assess antibiotic prescribing were; dose
      of prescribed antibiotic (low-dose, rational and high -dose) and Indication
      (valid or invalid). Antibiotics resistance for 25 selected antibiotics was
      determined by culture sensitivity test. This study showed that in Private Sector
      Hospital 77.7% neonates, 13.3% infants and 9% children admitted in ICU were
      receiving antibiotics, among them only 57.3% neonates, 62% infants and 59.9%
      children were found valid that is prescribed antibiotics for right indication.
      27% neonates, 19% infants and 22.1% children were prescribed under dose of
      antibiotics, which may lead to antimicrobial resistance and increased cost of
      hospital stay. Only 29.1% neonates, 30% infants and 36.8% children were receiving
      rational dosing. In Public Sector Hospital, 65.6% neonates, 19.4% infants and 15%
      children were receiving antibiotics. Among them valid indication was found in
      35.3% neonates, 35.6% infants and 39.8% in children. 33.3% neonates, 26.6%
      infants and 28.2% children were receiving under dose that may lead to resistance
      not only among those who were prescribed under dose but also such bacteria become
      resistant and spread to other population to increase antimicrobial resistance.
      The irrational prescribing of antibiotics was found very high (above 50%) in
      Public sector hospital (Hospital-B) for every age group whereas in Private sector
      hospital (Hospital-A) this practice was found near to 50%. In this study the
      prescribing frequency of Amikacin, Cefixime, Cefotaxime, Meropenem, Amoxicillin,
      Vancomycin, Azithromycin, Levofloxacin and Clarithromycin was found above 80% in
      both hospitals (A and B). Among these, Amoxicillin, Penicillin, Erythromycin and
      Cephalexin showed higher resistance i.e. 49.2%.

PMID- 29044003
TI  - Expression and significance of DDX43 in lung adenocarcinoma.
AB  - This paper aims to determine the expression and clinical significance of DDX43 in
      lung adenocarcinoma. Expression of DDX43 gene and protein of lung adenocarcinoma
      tissue and para-carcinoma tissues was observed in 27 cases by RT-PCR and
      immunohistochemistry. These patients were diagnosed as lung adenocarcinoma in the
      Huaihe Hospital of Henan University from February 2015 to December 2015. The
      relative ratio of DDX43 mRNA expression in lung adenocarcinoma and para-carcinoma
      tissues was 0.87+/-0.62 versus 0.21+/-0.77 and the difference between the two
      groups was statistically significant (P<0.01). The expression of DDX43 in normal
      lung tissues and lung adenocarcinoma tissues was different. The positive rate of
      DDX43 expression in lung adenocarcinoma tissues was significantly higher than
      that in normal lung tissues, and the difference was statistically significant
      (P<0.05). The analysis of clinical pathological characteristics showed that the
      increase of protein expression was related to the stage and metastasis of lung
      adenocarcinoma. DDX43 is highly expressed in lung adenocarcinoma, and the
      expression level is related to the stage and metastasis of lung adenocarcinoma,
      suggesting that DDX43 is closely related to the occurrence and development of
      lung adenocarcinoma, and may be a molecular marker for early diagnosis of lung
      adenocarcinoma.

PMID- 29044004
TI  - Research on the influence of bilateral oophorectomy on the BMD, body components
      and sex hormone of women during the perimenopause.
AB  - To investigate the effect of bilateral oophorectomy on bone mineral density, body
      composition and sex hormone of peri-menopause women. 33 cases of peri-menopause
      women patients performed bilateral oophorectomy were chosen from xxx gynaecology
      and obstetrics department of xxx hospital from January 1st,2014 to Dec31th, 2014.
      And the 33 cases were taken as ovariectomy group. 35 women who were the naturally
      postmenopausal after menopause collected in clinic and in the same period with
      the patients of ovariectomy group were taken in control group. American GE-Lunar
      Prodigy dual energy X-ray absorptiometry and chemiluminescence method were
      employed to detect the bone mineral density, fat content, muscle content and sex
      hormone of the patients in both groups at the 6th and 12th month after
      menostasis. There was no statistical significance on the comparative difference
      of bone mineral density, fat content and muscle content at the 6th and 12th month
      after menostasis between both groups, P>0.05. At the 6th month after menostasis,
      the estradiol (E2) level in ovariectomy group was significantly lower than that
      of control group [(14.79+/-22.17)U/L vs (32.74+/-31.02U/L)], P<0.05; at the 12th
      month after menostasis, it had the statistical significance for the comparative
      difference between the level of E2 and and follicle-stimulating hormone (FSH) in
      ovariectomy group and that in control group, E2: (8.09+/-4.38)U/L vs (25.92+/
      3.53)U/L; FSH: (64.88+/-18.39)U/L vs (40.69+/-31.63)U/L], P<0.05. the change of
      E2 and FSH were the main symptom of peri-menopausal women within 12 months after
      bilateral oophorectomy, the decrease of E2 level had no effect on bone mineral
      density, fat content and muscle content.

PMID- 29044005
TI  - Analysis on the treatment and prevention of epidemic conjunctivitis in 108 cases.
AB  - To explore the treatment method and preventive measures on epidemic
      keratoconjunctivitis. 108 patients with epidemic keratoconjunctivitis who
      received treatment in our hospital from January, 2015 to September, 2015.were
      selected. These patients were treated with interferon eye drops, Ganciclovir
      ophthalmic gel, and alternating eye treatment of tobramycin-dexamethasone eye
      drops and diclofenac sodium eye drops. Meanwhile, health education was also
      performed among patients, so as to promote the recovery of the disease as soon as
      possible and to prevent the spread of the disease Among the 108 patients, there
      were 101 patients recovered. 7 patients had cornea remained sub epithelial round
      hoary haze, including 2 patients with evident cornea remained sub epithelial
      round hoary haze due to the occurrence of glucocorticoid-induced intraocular
      pressure and the tobramycin and dexamethasone eye drops were suspend. The
      clinical cure rate was 91.79%. There was no pathophoresis to health patients
      among the 108 patients. Active treatment of epidemic keratoconjunctivitis,
      combined with health education and publicity could increase the clinical cure
      rate and control the transmit of the disease spread.

PMID- 29044006
TI  - Clinical efficacy of cryotherapy combined with interferon in the treatment of
      chronic cervicitis complicated with HPV infection.
AB  - This paper aims to investigate the clinical curative effect and adverse reactions
      of cryotherapy combined with interferon in the treatment of chronic cervicitis
      complicated with HPV infection. 100 cases diagnosed with chronic cervicitis
      complicated with HPV infection from August 2014 to August 2015 in our hospital
      were selected and randomly divided into observation group (50 cases) and control
      group (50 cases). The preoperative and postoperative HPV-DNA changes were
      observed, and the vaginal discharge, time of decrustation and hemostasis, HPV
      negative conversion ratio and clinical efficacy were compared, to record the
      adverse reactions during treatment. After treatment, the level of RLU/CO value of
      the observation group was significantly lower than that of the control group
      (P<0.05); the vaginal discharge and time of decrustation and hemostasis of the
      observation group were shorter than that of the control group (P<0.05); 3 months
      after treatment, the HPV negative conversion ratio in the observation group was
      significantly higher than that in the control group; the total efficiency of the
      observation group was higher than that of the control group, with statistical
      significance (P<0.05). There were no serious adverse reactions in the two groups
      during the treatment. The efficiency of cervicitis complicated with HPV infection
      in the treatment of cryotherapy combined with interferon was more significantly.
      It can effectively reduce the load of HPV, promote the recovery of patients with
      pathological changes. Therefore, it is worth promoting.

PMID- 29044007
TI  - Depressive symptoms, monoamines levels, MAO-B activity and effect of treatment in
      a subset of depressed individuals from government sector hospital at Karachi.
AB  - Depression is one of the leading causes of disability in developing countries
      including Pakistan. This study was designed to assess the frequency and severity
      of depressive symptoms, monoamines and their metabolite levels, MAO-B activities
      before and after treatment with antidepressants in a sub-set of Karachi
      population in Pakistan. Drug naive depressed subjects were evaluated before and
      after treatment with selective serotonin reuptake inhibitors. Symptoms of
      depressed mood and anxiety psychic (90%) were more frequent whereas, suicidal
      thoughts (~50%) and feelings of guilt (~30%) were less common. Hamilton
      Depression Rating Scale scores were 21.4 +/- 0.8 in both genders with a
      significantly higher score (1.3x) in females. Homovanillic acid, 5-
      hydroxyindoleacetic acid and MAO-B activity were significantly higher 43%, 66%
      and 25% respectively, in depressed than normal subjects. A significant decline
      after 2 weeks treatment in HDRS scores with fluoxetine (19%) and paroxetine (40%)
      and in MAO-B activity (20%) was observed. In conclusion, in our population early
      decline in HDRS scores supports that they are SSRIs responders, whereas a
      concomitant reduction in MAO-B activities indicates that it can be considered as
      one of the parameters for early detection of response. Additionally, the low
      frequency of suicidal thoughts could be associated with higher levels of
      monoamine metabolites.

PMID- 29044008
TI  - Analysis of the effect of paclitaxel-eluting stents and paclitaxel-eluting
      balloon in the treatment of in-stent restenosis.
AB  - To compare and analyze the effect and the safety of the paclitaxel-eluting stents
      and paclitaxel-eluting balloon in the treatment for in-stent rest enosis. 120
      cases, who had been undergone percutaneous coronary intervention (PCI) in the
      Department of Cardiology of Henan Provincial People's Hospital from January 2012
      to January 2014 were selected. All the patients were randomly treated with
      paclitaxel-eluting balloon or paclitaxel-eluting stents. The former were divided
      into different groups that named group A and the later group B. All the selected
      patients signed the informed consent on interventional therapy and be given anti
      platelet drugs before operating. At the same time, they had routine examination,
      like chest X-ray, ultrasound, biochemical detection, Myocardial injury markers.
      (1) The two groups had no significant difference in the general information
      (P>0.05); (2) The success rate in the two groups reached 100% and (3) All the
      patients were visited in the 9th, 12th and 24th month to see if any of them was
      dead. The reexamination results in the 9th month showed that both drug-eluting
      balloon and drug-eluting stents were safe and effective in treating coronary
      artery in-stent restenosis. In addition, drug-eluting balloon was more effective
      than drug-eluting stents to prevent from the in-stent restenosis.

PMID- 29044009
TI  - [Stability of Candid#1 vaccine to prevent Argentine Hemorrhagic Fever].
AB  - Candid#1 is the first live attenuated vaccine produced and registered in
      Argentina. Produced since 2003 at the INEVH to prevent Argentine hemorrhagic
      fever, it is obtained by harvesting supernatants of diploid cells infected with
      an attenuated strain of Junin virus and subsequent lyophilization. The stability
      of this vaccine is crucial to ensure its effectiveness. This study was aimed to
      evaluate the stability of Candid#1 by exposing it to different time and
      temperature conditions. Three vaccine batches produced in 2003 were analysed
      according to the following storage scheme: (a) reconstituted vaccine at 2 
      degrees C to 8  degrees C for 8 days; (b) lyophilized vaccine at 2  degrees C to
      8  degrees C for 6 months; (c) lyophilized vaccine at -18  degrees C to -20 
      degrees C for 10 years. The potency was assessed in Vero cell monolayers under
      agar. The results were: (a) reconstituted vaccine was stable between 2  degrees C
      and 8  degrees C for 8 days, (b) lyophilized vaccine was stable between 2 
      degrees C and 8  degrees C for 2 months, and (c) lyophilized vaccine was stable 9
      years between -18  degrees C and -20  degrees C, keeping all its properties.
      These results allowed us to establish the following storage conditions and
      expiration times for Candid#1: (a) reconstituted: 12 hours between 2  degrees C
      and 8  degrees C, (b) lyophilized: 30 days between 2  degrees C and 8  degrees C
      and (c) lyophilized: 9 years between -18  degrees C and -20  degrees C. Based on
      our results, favorable changes were made in the conditions of transport, storage
      and distribution of the vaccine. Domestic freezers in strategically located
      centers were installed, allowing the preservation of vaccine stocks for
      distribution to secondary vaccination centers.

PMID- 29044010
TI  - [Simple mechanical reperfusion in acute myocardial infarction: determinants,
      prognostic implications and relation with thrombus histology].
AB  - Simple mechanical reperfusion (SMR) is defined as reperfusion achieved after wire
      insertion at the occluded infarct-related artery in primary angioplasty. The
      determinants and prognostic implications of SMR and its relationship with the
      histopathology of the rescued thrombus were evaluated in 601 patients with acute
      myocardial infarction showing ST elevation and pre-procedural total occlusion of
      the infarct-related artery (TIMI flow 0). Two groups were considered according to
      the presence of SMR, defined as the visualization of contrast material after
      crossing the occlusion with the guide wire. SMR was achieved in 303 patients
      (50.4%) and was found to be associated with less time to treatment (248 vs. 286
      minutes; p = 0.001), less deteriorated initial left ventricular function and
      shock at admission (9.2 vs. 16.4%; p = 0.008), higher successful rate (94.7% vs.
      78.5%; p < 0,0001) and of higher rate of thrombus rescue: 70/81 vs. 27/79
      patients (p < 0.0001). The right coronary artery was the most frequent infarct
      related artery. Histopathology of the retrieved thrombi was available for 160
      patients treated with thrombus aspiration. SMR was associated with smaller
      thrombus, lower contents of leukocytes and erythrocytes, and higher thrombus
      content of inflammatory cells, cholesterol and collagen crystals from the
      atheromatous plaque. SMR is an independent predictor of procedure success and its
      relationship with the anatomy of the thrombus could redefine the indication of
      thrombus aspiration.

PMID- 29044011
TI  - Antiretroviral therapy and arterial elasticity in HIV-infected patients.
AB  - Cardiovascular risk is increased in HIV-infected patients and has become a
      leading cause of morbi-mortality in this population. The purpose of this study is
      to compare HIV-infected patients on antiretroviral therapy (ART) and ART-naive
      HIV-infected patients regarding arterial elasticity. From September 2010 to
      September 2015, 105 HIV-infected subjects were enrolled, 41 ART-naive and 64 on
      ART with stable viral suppression. Elasticity of large and small arteries (LAE
      and SAE) was assessed by analysis of radial pulse waveforms using a calibrated
      device. A single set of measurements was performed. Multivariate linear
      regression models were constructed to estimate independent correlates of arterial
      elasticity. On-ART and ART-naive patients were similar with respect to gender,
      age, body mass index, Framingham cardiovascular risk score, smoking habits, and
      CD4+ counts. Median time on treatment was 60 months and 79% of patients were on
      regimens based on non-nucleoside reverse-transcriptase inhibitors. No significant
      differences in LAE and SAE assessments were found between groups. However, time
      on ART and cholesterol levels were independently associated with LAE impairment.
      No association between arterial elasticity and CD4+ counts was found. We conclude
      that cumulative exposure to ART may play a role on LAE impairment and deserves
      further investigation.

PMID- 29044012
TI  - [Gastrointestinal stromal tumors. Analysis of 40 cases].
AB  - Gastrointestinal stromal tumors represent less than 3% of all digestive tumors.
      They are primarily located in the stomach and the small intestine. The curative
      treatment is surgical resection. In the case of unresectable tumor or advanced
      disease, imatinib is the treatment of choice. The purpose of this retrospective
      study was to describe the characteristics of patients with gastrointestinal
      stromal tumors treated at our institution in the period 2000-2015. We analyzed 40
      consecutive patients diagnosed with gastrointestinal stromal tumor (mean age 58
      year old, range 33-84). The mean 5-year survival was 30.5%. At diagnosis, 30
      patients had localized disease (75%); 14 of them received adjuvant imatinib and
      15 follow-up on observation. In this group the disease-free interval was 55
      months. In patients with advanced disease, the progression-free interval was 30
      months.

PMID- 29044013
TI  - [Acute aortic regurgitation due to infective endocarditis].
AB  - Acute aortic regurgitation (AAR) due to infective endocarditis (IE) is a serious
      disease and usually requires surgical treatment. Our study aims to compare the
      clinical, echocardiographic, and microbiological characteristics as well as in
      hospital outcome of patients with AAR according to the severity of heart failure
      (HF) and to evaluate predictors of in-hospital mortality in a tertiary centre. In
      a prospective analysis, we compared patients with NYHA functional class I-II HF
      (G1) vs. functional class III-IV HF (G2). From 06/92 to 07/16, 439 patients with
      IE were hospitalized; 86 presented AAR: (G1, 39: 45.4% y G2, 47: 54.7%). The G1
      had higher prosthetic IE (43.6% vs. 17%, p 0.01). All G2 patients had dyspnoea
      vs. 30.8% of the G1 (p < 0.0001). There were no differences in clinical,
      echocardiographic and microbiological characteristics. Surgical treatment was
      indicated mainly due to infection extension or valvular dysfunction in G1 and HF
      in G2. In-hospital mortality was 15.4% vs. 27.7% (G1 and G2 respectively p NS).
      In multivariate analysis, health care-associated acquisition (p 0.001), negative
      blood cultures (p 0.004), and functional class III-IV HF (p 0.039) were in
      hospital mortality predictors. One-fifth of the patients with EI had AAR. Half of
      them had severe HF which needed emergency surgery and the remaining needed
      surgery for extension of the infection and / or valvular dysfunction. Both groups
      remain to have high surgical and in-hospital mortality. Health care-associated
      acquisition, negative blood cultures and advanced HF were predictors of in
      hospital mortality.

PMID- 29044014
TI  - [Anaphylaxis and allergic reactions during surgery and medical procedures].
AB  - Anaphylaxis during anesthesia is an unpredictable, severe, and rare reaction. It
      has an incidence of 1/10 000 to 1/20 000 surgeries. In most series, the
      responsible drugs include neuromuscular blocking agents, latex, or antibiotics.
      The frequency and etiology of systemic allergic reactions in other medical
      procedures are largely unknown. The identification of responsible drugs of
      anaphylaxis is a complex task, requiring testing of all medications and
      substances used during surgery. We describe our experience in a retrospective
      study of 15 patients. Ten subjects developed anaphylaxis during surgery, two in
      endoscopic studies and one in a trans-vaginal ultrasound. The remaining two
      subjects, one in a trans-vaginal ultrasound and another during a dental procedure
      had a systemic allergic reaction. We studied all patients with all medications
      administered during the procedures, including latex and detergents and
      disinfectants. Three surgeries had to be suspended at induction of anesthesia,
      five were stopped incomplete and two were completed. Both patients that presented
      a reaction during endoscopy required intensive care unit admission and the rest
      were observed in a Hospital. The responsible drugs during surgery anaphylaxis
      were neuromuscular blocking agents, latex, patent blue, and ranitidine. Ortho
      phthalaldehyde (OPA) was identified during endoscopic studies; latex was
      responsible in transvaginal ultrasounds; and amoxicillin in the dental procedure.
      The aim of the present article is to review our experience studying allergic
      systemic reactions and anaphylaxis during general anesthesia and medical
      procedures, emphasizing the severity of these reactions and the need for
      causative drug identification.

PMID- 29044015
TI  - [Argentina enacts first law on medical use of the cannabis plant. History and
      perspectives].
AB  - In the last few years, great expectations have risen in the society concerning
      the eventual therapeutic usefulness of compounds derived from the cannabis plant.
      It is well known that these compounds are being used in treating certain health
      conditions, either through medical prescription or self-administration. Extreme
      opinions range from believing that it is a harmful and dangerous drug to
      sustaining that it is a panacea. However, the sheer existence of an
      endocannabinoid system in the brain compels us to study its dimensions and
      derivations thoroughly. It is expected that controversies and knowledge gaps will
      be clarified within the framework of this new law. Prohibitionism should not be a
      category of analysis. Regardless of the therapeutic effects of cannabinoid
      compounds, demonstrated or to be demonstrated, there are already severe
      restrictions on their use, which mirror the still existing restrictions to the
      use of opioids (drugs of definite utility but on which a huge taboo persists).
      This review presents the first Argentine law on the medical use of cannabis.
      Milestones in the history of marijuana at the national level are pointed out,
      which are inextricably linked to world trends either in favor or against
      prohibition. The current status of the use of cannabis oil in the country and
      evidences for its therapeutic value are also analyzed. Evidences on its
      therapeutic value are also analyzed as well as the current status of the use of
      cannabis oil in our country.

PMID- 29044016
TI  - Drug-induced hypothyroidism.
AB  - The thyroid axis is particularly prone to interactions with a wide variety of
      drugs, whose list increases year by year. Hypothyroidism is the most frequent
      consequence of drug-induced thyroid dysfunction. The main mechanisms involved in
      the development of primary hypothyroidism are: inhibition of the synthesis and/or
      release of thyroid hormones, immune mechanisms related to the use of interferon
      and other cytokines, and the induction of thyroiditis associated with the use of
      tyrosine kinase inhibitors and drugs blocking the receptors for vascular
      endothelial growth factor. Central hypothyroidism may be induced by inhibition of
      thyroid-stimulating hormone (bexarotene or corticosteroids) or by immunological
      mechanisms (anti-CTLA4 or anti-PD-1 antibody drugs). It is also important to
      recognize those drugs that generate hypothyroidism by interaction in its
      treatment, either by reducing the absorption or by altering the transport and
      metabolism of levothyroxine. Thus, it is strongly recommended to evaluate thyroid
      function prior to the prescription of medications such as amiodarone, lithium, or
      interferon, and the new biological therapies that show important interaction with
      thyroid and endocrine function in general.

PMID- 29044017
TI  - [CRISPR/Cas9 and gene therapy].
AB  - The development of techniques that allow the precise and efficient edition of the
      genome of living cells is one of the main goals of biomedical research. Over the
      last few decades, a number of genome editing tools have been developed, the most
      prominent being the CRISPR/Cas9 system, a bacterial defense mechanism that has
      been redesigned for its use in other cellular systems. The accessibility, both
      technical and economical, and the enormous potential of CRISPR/Cas9 have
      contributed to an almost unprecedented revolution in the biomedical sciences and
      represent an important step forward in the field of gene therapy that needs,
      however, to be taken cautiously.

PMID- 29044018
TI  - [Insulin therapy in special conditions].
AB  - Hyperglycemia during hospitalization is a common condition associated with poor
      prognosis. To date, insulin is the best strategy to treat hyperglycemia in these
      patients. An adequate glycemic control is associated with better clinical
      results. Nevertheless, glycemic goals are still controversial due to the increase
      of hypoglycemia and other adverse events. Diabetes mellitus is still the main
      cause of chronic renal failure in our country and its treatment deserves a
      special analysis considering that insulin pharmacokinetics is altered.
      Recommendations in this setting are based in expert panel opinions, focusing
      mainly in intermediate or long acting insulins combined with regular insulin
      and/or rapid acting analogues. During pregnancy, NPH and regular insulin are safe
      and effective. It is worth mentioning that the development of new long and rapid
      acting molecules yielded lower glycemic variability, better post-prandial control
      and less hypoglycemia. The aim of this study is to provide a review of the proper
      use of insulin in these special conditions.

PMID- 29044019
TI  - [Thickening of the posterior paratracheal line due to esophageal cancer].

PMID- 29044020
TI  - [Generalized pneumatosis].

PMID- 29044021
TI  - [ASIA syndrome: breast implant and Still's disease].
AB  - Connective tissue diseases associated with silicone breast implants have been
      widely discussed. In the last decade, siliconosis has been included in the
      autoimmune/inflammatory syndrome induced by adjuvants (ASIA) next to Gulf War
      syndrome, macrophage myofascitis and postvaccination phenomena. The ASIA syndrome
      may appear as lupus, rheumatoid arthritis, or more rarely, as adult Still's
      disease. We discuss the case of a patient with prolonged fever and clinical
      criteria for ASIA and Still's disease. The prostheses were resected and pathology
      showed absence of breast implant associated anaplastic lymphoma ALK (-).
      Physicians should be alert to these new entities linked to silicone breast
      implants.

PMID- 29044022
TI  - [Villaret syndrome and lung adenocarcinoma: an unusual association].
AB  - Villaret syndrome is defined by the affection of the glossopharyngeal (IX), vagal
      (X), accessory (XI) and hypoglossal (XII) cranial nerves associated with
      ipsilateral Horner syndrome. It is caused by the compression of these nerves and
      the neighboring sympathetic plexus fibers at the base of the skull, particularly
      in the retroparotid space. Even though the invasion of the central nervous system
      in patients with advanced lung cancer is a frequent and well known occurrence,
      this particular symptomatic association is extremely rare. We are reporting the
      case of a newly diagnosed lung adenocarcinoma patient who is simultaneously
      developing this syndrome.

PMID- 29044023
TI  - [May Thurner syndrome with ischemic cerebrovascular accident and permeable oval
      foramen].
AB  - The association of cerebral ischemic attack with patent foramen ovale has not
      been extensively studied, and frequently the site of origin of embolism is not
      detected despite routine studies. We present the case of a young patient with
      ischemic stroke and permeable oval foramen in the context of May Thurner
      syndrome. The May Thurner syndrome is an entity scarcely studied in the medical
      literature and it has also been infrequently related to ischemic vascular
      cerebral accident, but in patients with permeable oval foramen without evidence
      of the emboligen source, it is interesting to rule it out as a cause of
      paradoxical embolism.

PMID- 29044024
TI  - [Induction of atrioventricular nodal reentrant tachycardia by radiofrequency
      application].
AB  - Atrioventricular nodal reentrant tachycardia is the most common form of sustained
      regular narrow QRS complex tachycardia. It is caused by the presence of a dual
      atrioventricular nodal anatomy and physiology, with a fast and a slow pathway
      forming a substrate for re-entry. Electrophysiology study confirms the diagnosis
      when the tachycardia is induced, although in some cases this is not possible.
      Casuistry is here presented where the application of radiofrequency induced
      atrioventricular nodal reentrant tachycardia, when the electrophysiological study
      could not do it; we explain here its electrophysiological mechanism.

PMID- 29044025
TI  - [Screening of breast cancer. Certainties and controversies].

PMID- 29044026
TI  - [Opus posthumous].

PMID- 29044027
TI  - [Science and technology in Argentina according to the World Bank].

PMID- 29044028
TI  - [Rodolfo Viotti: clinical investigator in Chagas disease (1959-2017)].

PMID- 29044030
TI  - [Vitamin D - for everyone[Editorial]].

PMID- 29044031
TI  - [General Practice - new challenges with classical core[Editorial]].

PMID- 29044032
TI  - [The relationship between serum vitamin D levels and cardiovascular risk factors
      among Icelandic children].
AB  - OBJECTIVE: To determine the relationship between serum vitamin D levels and known
      cardiometabolic risk factors among healthy Icelandic children as well as study
      these connections independent of body mass index (BMI). METHODS: We assessed the
      relationship between serum 25-hydroxyvitamin D, adiposity measured as BMI and 7
      cardiometabolic risk factors (high blood pressure, total cholesterol, high
      density lipoprotein cholesterol, low-density lipoprotein cholesterol,
      triglycerides, blood glucose and serum insulin). Subjects were 7-year old school
      children in six randomly selected elementary schools in Reykjavik, Iceland, in
      the autumn of 2006. RESULTS: Vitamin D was measured amongst 159 children. 35
      (22%) were lower than 37,5 nmol/L, 70 (44%) between 37,5-50,0 nmol/L and 55 (34%)
      over 50 nmol/L. Deficiency was defined as lower than 37,5 nmol/L. No difference
      was between girls or boys, girls (n:85 = 44,2nmol/L), boys (n:74 = 46,9nmol/L),
      (p= 0,052). Deficient children had higher BMI (p=0.052), lower HDL (p=0.044) and
      higher HbA1c (p=0.015), and insulin (p=0.014) than those who had vitamin D higher
      than 50 nmol/L. Significant correlation was between low levels of vitamin D and
      high levels of serum insulin (p=0,014) and high levels of HbA1c (p =0,015),
      independent of BMI. CONCLUSION: Vitamin D deficiency has been associated with the
      development of cardiovascular disease. It is important to explore the connection
      between known risk factors and vitamin D and treat those who are deficient of it,
      especially children and young adults. It is possible that vitamin D deficiency
      has an effect on cardiovascular risk early in life through insulin resistance and
      altered blood sugar control. It is important to follow guidelines for giving
      vitamin D to children, as the result showed that 2/3 of the children were under
      50 nmol/L. Key words: Vitamin D, cardiovascular risk factors, insulin
      Correspondence: Emil L. Sigurdsson emilsig@hi.is.

PMID- 29044029
TI  - Determining residual adipose tissue characteristics with MRI in patients with
      various subtypes of lipodystrophy.
AB  - PURPOSE: We aimed to investigate residual adipose tissue with whole-body magnetic
      resonance imaging to differentiate between subtypes of lipodystrophy. METHODS: A
      total of 32 patients (12 with congenital generalized lipodystrophy [CGL], 1 with
      acquired generalized lipodystrophy [AGL], 12 with familial partial lipodystrophy
      [FPLD], and 7 with acquired partial lipodystrophy [APL]) were included. RESULTS:
      Despite generalized loss of metabolically active adipose tissue, patients with
      CGL1 caused by AGPAT2 mutations had a significant amount of residual adipose
      tissue in the scalp, earlobes, retro-orbital region, and palms and soles. No
      residual adipose tissue was noted particularly in the head and neck, palms and
      soles in CGL2 caused by BSCL2 mutations. CGL4 caused by mutations in the PTRF
      gene was characterized with well-preserved retro-orbital and bone marrow fat in
      the absence of any visible residual adipose tissue in other areas. No residual
      adipose tissue was observed in AGL. Despite loss of subcutaneous fat,
      periarticular adipose tissue was preserved in the lower limbs of patients with
      FPLD. Retro-orbital adipose tissue was surprisingly preserved in APL, although
      they lacked head and neck fat. CONCLUSION: Lipodystrophies are a heterogeneous
      group of disorders characterized by generalized or partial loss of adipose
      tissue, which can be congenital or acquired. Our results suggest that residual
      adipose tissue characteristics can help distinguish different subtypes of
      lipodystrophy.

PMID- 29044033
TI  - [Reduction of shoulder dislocation with the Cunningham method].
AB  - INTRODUCTION: The Cunningham technique has been shown to be an effective and
      simple method to reduce a dislocated shoulder. It is based on the theory that the
      humeral head remains outside the glenoid fossa due to tension in the long biceps
      tendon. In the beginning of 2013 doctors at the emergency department in
      Landspitali University Hospital (LUH) in Reykjavik were instructed in the
      Cunningham method for reduction of anterior dislocation without sedation. The
      goal of this retrospective study was to evaluate the impact of its induction with
      regards to number of attempts, successful relocations, sedation, use of
      analgesics and length of stay in the ED. MATERIAL AND METHODS: We searched our
      electronic database for patients coming to the ED in LUH in 2012 and 2013 with
      anterior shoulder dislocation. Information was obtained on age and gender, the ED
      length of stay, first to fourth attempted methods of reduction, medications given
      for pain relief and sedation and whether this was the first dislocation or not.
      We used descriptive statistics and comparing the two groups we used independent
      sample t-test or chi-square to calculate the p-value. RESULTS: During the study
      period, a reduction was attempted on 190 patients with a shoulder dislocation
      with 95% of dislocations successfully reduced in the ED. The proportion of
      patients on which the Cunningham method was applied on first attempt increased
      from 1% to 27% between years. Average number of attempts was 1.15 in the first
      year and 1.38 the second year (p = 0.002). The proportion of successful first
      attempts fell from 81.6% to 66% (p = 0.016) but successful relocation in the
      emergency department after all attempts was 93.1% and 97.1%, respectively (p =
      0,305). The duration of treatment was similar between years or 226 and 219
      minutes (p = 0,839). Sedation ratio decreased from 85.1% to 73.8% (p = 0.024) and
      use of analgesics was similar between years, 70.6% and 69.6% (p = 0.843).
      CONCLUSION: Induction of the Cunningham method resulted in a significant
      reduction in the need for sedation. It reduced the rate of successful relocations
      in the first attempt and increased the number of attempts to but had no effect on
      the length of stay in the emergency room or the overall rate of successful
      relocations. Key words: Cunningham, shoulder, dislocation, reduction
      Correspondence: Hjalti Mar Bjornsson hjaltimb@landspitali.is.

PMID- 29044034
TI  - [50th anniversary of the Reykjavik Heart Study[Editorial]].

PMID- 29044035
TI  - [The Aging, Genes and Environment Susceptibility Reykjavik Study[Editorial]].

PMID- 29044036
TI  - [Five decades of coronary artery disease in Iceland. Data from the Icelandic
      Heart Association].
AB  - Coronary artery disease has been the leading cause of death and disability in
      Iceland during the past decades although in recent years, malignancy has taken
      over that position. A steady improvement in the level of major risk factors has
      been evident since 1980. This trend explains 72% of the decrease in premature
      mortality from coronary artery disease during the past three decades. However, an
      opposing trend in increasing obesity and type 2 diabetes has attenuated this
      decline in premature deaths. Unchanged risk factor trends will lead to increasing
      cardiovascular mortality in the years to come. This will result from the above
      mentioned changes in major risk factors as well as an increased ageing of the
      Icelandic population. At the same time case fatality after myocardial infarction
      has declined substantially. This will result in a steadily growing proportion of
      elderly in the population as well as a high burden of chronic non-communicable
      diseases among the elderly population. The resulting increase in long term
      disease and disability will put a major constraint on the health care system and
      economy alike. According to vital statistics and secular trends the rate of
      Icelanders in working age for each one reaching retirement age will decrease from
      the current 5.6 to 2.6 by year 2060. This paper addresses the driving factors of
      risk factor change in Iceland with previously unpublished data extending to 2013.

PMID- 29044037
TI  - [Review of epidemiology of fractures in the Icelandic Heart Association cohort].
AB  - IIn recent years, scientific papers have been published in Osteoporosis
      International on the epidemiology of fractures in Iceland based on the Icelandic
      Heart Association cohort. We report the main results with emphasis on the major
      osteoporotic fractures (MOF), distal forearm, upper arm, clinical vertebral and
      hip. Those four types of fractures have been reported to cause about 90% of the
      total burden of all osteoporotic fractures. The incidence of those four fractures
      in the Icelandic Heart Association cohort have been used as the basis for the
      international fracture risk calculator "FRAX "in Iceland. "FRAX" assesses the
      risk of those fractures for the next 10 years in both sexes in the age group 40
      90 years. FRAX Iceland was opened on the internet in the year 2013. We emphasize
      the importance of previous fracture history as almost 40% of all major
      osteoporotic fractures occur after first MOF according to our cohort. The results
      demonstrate the importance of time from the first fracture as the risk of the
      second fracture is greater in the first two years although increased risk remains
      during the next 20 years. This indicates the importance of secondary prevention
      early after the first fracture especially amongst elderly people. These results
      give a good overall view about the epidemiology of fractures in Iceland in
      comparison with foreign studies and shows that age standardized incidence of the
      most important osteoporotic fracture, the hip fracture, reached a maximum around
      the millennium but has decreased among women until 2008 similar to what has been
      observed in Sweden and Denmark.

PMID- 29044038
TI  - [Heart failure among elderly Icelanders: Incidence, prevalence, underlying
      diseases and long-term survival].
AB  - INTRODUCTION: Heart failure (HF) is a common and a serious condition that
      predominantly affects elderly people. On the basis of the left ventricular
      ejection fraction (EF) it can be divided into HF with reduced or preserved
      ejection fraction (HFrEF and HFpEF, respectively). The goal of this study was to
      investigate the prevalence and incidence of HF among elderly Icelanders, explore
      underlying diseases and estimate the effect of HF on overall survival. MATERIAL
      AND METHODS: Included were 5706 participants of the AGES study. The hospital
      records of those diagnosed with HF before entry into AGES were used to calculate
      prevalence and the records of those diagnosed from entry into AGES until
      28.2.2010 were used to calculate incidence. All cases of HF were verified
      according to predetermined criteria for diagnosis. Information on underlying
      diseases and EF of HF patients were obtained from hospital records. Survival was
      estimated using Kaplan-Meier survival curves. RESULTS: Lifetime prevalence of HF
      was 3.6% as of 2004, higher among men than women (p<0,001). The incidence was
      16.2 cases per 1000 person-years, higher among men than among women (p<0,001).
      The incidence of HFrEF was 6.1 per 1000 person-years also higher among men than
      women (p<0,001). The incidence of HFpEF was 6.8 per 1000 person-years and there
      was no statistical difference between the sexes (p=0.62). The age adjusted 5-year
      survival rate of HF-patients was 32.5%, there was no statistical difference in
      relative survival between men and women (p=0.46). There was no statistical
      difference between the survival of patients with HFrEF and those with HFpEF
      (p=0.52). CONCLUSION: Both prevalence and incidence of HF are high among elderly
      Icelanders, increasing sharply with age and 5-year survival rate is only around
      30%. While men are more likely to develop HF, especially HFrEF, women are more
      likely to be diagnosed with HFpEF.

PMID- 29044039
TI  - Myxobolus arcticus and Parvicapsula minibicornis infections in sockeye salmon
      Oncorhynchus nerka following downstream migration in British Columbia.
AB  - Factors influencing the health of sockeye salmon Oncorhynchus nerka in British
      Columbia, Canada, are important for fisheries management and conservation.
      Juvenile salmon originating from the Fraser River were screened for 3 enzootic
      parasites (Myxobolus arcticus, Parvicapsula minibicornis, Ceratonova shasta) and
      the bacterium Renibacterium salmoninarum. Fish were collected from the Strait of
      Georgia in 2010, 2011 and 2012 and genotyped to stock of origin. Trends in
      infection status were estimated by year, spawning zone and catch area. The annual
      prevalences of P. minibicornis (n = 1448) were 23.3, 6.5 and 8.1%, and for M.
      arcticus (n = 1343), annual prevalences were 40.4, 66.3 and 27.4%, respectively.
      Logistic regression showed that P. minibicornis was most strongly associated with
      salmon from the lower Fraser River spawning zone and increased with distance
      caught from the mouth of the Fraser River. In contrast, infection with M.
      arcticus was most strongly associated with salmon from the middle Fraser River
      spawning zone, and there was no trend related to distance from the Fraser River.
      Neither R. salmoninarum nor C. shasta were detected. These observations are
      discussed in the context of salmon life history and pathogen biology.

PMID- 29044040
TI  - Epizootiology of the ectoparasitic protozoans Ichthyobodo salmonis and Trichodina
      truttae on wild chum salmon Oncorhynchus keta.
AB  - Infestations of the ectoparasitic flagellate Ichthyobodo salmonis and the ciliate
      Trichodina truttae have caused acute mortalities of hatchery-reared juvenile chum
      salmon Oncorhynchus keta in Hokkaido, northern Japan. This study examined the
      epizootiology of I. salmonis and T. truttae on wild chum salmon as a possible
      infection source of the 2 parasitic protozoans in hatcheries. Infestations by
      both ectoparasites were detected on freshwater-adapted adult and juvenile chum
      salmon in all 4 rivers examined. This is the first study of an anadromous Pacific
      salmonid to report infestation of I. salmonis and T. truttae in adults returning
      for spawning. Among the marine-inhabiting phase of chum salmon, infestation with
      I. salmonis, but not T. truttae, was observed on adults and juveniles. The 2
      protozoans were experimentally transmitted at the same time from wild to hatchery
      reared chum salmon juveniles, and caused a high rate of mortality in the hatchery
      fish. In freshwater, the proliferation rate of T. truttae was greater than that
      of I. salmonis. These observations show that the euryhaline ectoparasite I.
      salmonis can infest chum salmon throughout their life cycle, in both river and
      ocean habitats, whereas T. truttae is able to infest these salmonids only in
      freshwater. Furthermore, wild chum salmon were shown to be a potential
      infestation source for both T. truttae and I. salmonis in hatchery fish.

PMID- 29044041
TI  - Viral haemorrhagic septicaemia virus (VHSV Id) infections are detected more
      consistently using syndromic vs. active surveillance.
AB  - The eradication of viral haemorrhagic septicaemia virus (VHSV Id) from Finnish
      brackish-water rainbow trout Oncorhynchus mykiss farms located in the restriction
      zone in the Province of Aland, Baltic Sea, failed several times in the 2000s. The
      official surveillance programme was often unable to find VHSV-positive
      populations, leading to the misbelief in the fish farming industry that virus
      eradication could be achieved. The ability of 3 other surveillance programmes to
      detect infected fish populations was compared with the official programme. One
      programme involved syndromic surveillance based on the observation of clinical
      disease signs by fish farmers, while 2 programmes comprised active surveillance
      similar to the official programme, but included increased sampling frequencies
      and 2 additional tests. The syndromic surveillance concentrated on sending in
      samples for analysis when any sign of a possible infectious disease at water
      temperatures below 15 degrees C was noticed. This programme clearly outperformed
      active surveillance. A real-time reverse transcriptase-polymerase chain reaction
      method proved to be at least as sensitive as virus isolation in cell culture in
      detecting acute VHSV infections. An ELISA method was used to test fish serum for
      antibodies against VHSV. The ELISA method may be a useful tool in VHSV
      eradication for screening populations during the follow-up period, before
      declaring an area free of infection.

PMID- 29044042
TI  - Experimental inoculation of oriental river prawn Macrobrachium nipponense with
      white spot syndrome virus (WSSV).
AB  - The oriental river prawn Macrobrachium nipponense is an economically important
      species that is widely farmed in China. White spot syndrome virus (WSSV) is one
      of the most devastating pathogens of the cultured shrimp Litopenaeus vannamei,
      responsible for massive loss of its commercial products worldwide. We
      investigated the infectivity and pathogenicity of WSSV in adult M. nipponense
      using standardized conditions for L. vannamei. The median lethal dose of WSSV in
      adult M. nipponense was 103.84+/-0.06 copies g-1, which was about 1000-fold
      higher than in L. vannamei (100.59+/-0.22 copies g-1). WSSV was detected by 2
      step PCR in the gills, hepatopancreas, muscle, stomach, heart, gut, nerve,
      integument, pereopod, eyestalk, testis, and ovary of experimentally infected dead
      M. nipponense. Lesions were observed histologically following WSSV injection,
      showing basophilic intranuclear inclusion bodies in the hepatopancreas and
      subsequently in the gills. The clearance of WSSV was observed in hepatopancreas
      and gills at 48 and 96 h post-inoculation, respectively. No histological lesions
      were detected in muscle from 0-96 h post-injection. The results show that the
      oriental river prawn M. nipponense can be infected by WSSV and the infections are
      self limiting over time; therefore, M. nipponense may serve as a useful model for
      studying resistance to WSSV.

PMID- 29044043
TI  - Nutrient availability modulates both host and parasite life histories in a snail
      trematode interaction.
AB  - Host nutrient availability can have important life history consequences for hosts
      and their parasites. The responses of each participant within the association can
      vary extensively across host-parasite systems. In this paper, we outline the life
      history responses of the aquatic snail Biomphalaria glabrata and its trematode
      parasite Echinostoma caproni during host nutrient restriction. The onset of host
      starvation had rapid and strong effects on snail reproduction, significantly
      reducing egg output in control snails and eliminating egg production in infected
      individuals. The combination of E. caproni infection and nutrient restriction
      also had a dramatic effect on B. glabrata survival, with starved infected snails
      dying at a faster rate than hosts from any other treatment. In terms of parasite
      reproduction, host nutrient restriction did not influence the quantity of
      parasite larvae produced after starvation onset but did influence parasite
      quality, reducing both larval swimming time and overall longevity. Together these
      results demonstrate that nutrient restriction can strongly influence both host
      and parasite life histories, and therefore should be considered in future studies
      attempting to understand patterns of disease in host populations.

PMID- 29044044
TI  - Seawater detection and biological assessments regarding transmission of the
      oyster parasite Mikrocytos mackini using qPCR.
AB  - Mikrocytos mackini is an intracellular parasite of oysters and causative agent of
      Denman Island disease in Pacific oysters Crassostrea gigas. Although M. mackini
      has been investigated for decades, its natural mode of transmission, mechanism
      for host entry, and environmental stability are largely unknown. We explored
      these biological characteristics of M. mackini using a recently described
      quantitative PCR (qPCR) assay. We detected M. mackini in the flow-through tank
      water of experimentally infected oysters and during disease remission in host
      tissues following 6 wk of elevated water temperature. Waterborne exposure of
      oysters to M. mackini further confirmed the potential for extracellular seawater
      transmission of this parasite and also identified host gill to have the highest
      early and continued prevalence for M. mackini DNA compared to stomach, mantle,
      labial palps, or adductor muscle samples. However, infections following
      waterborne challenge were slow to develop despite a substantial exposure (>106 M.
      mackini l-1 for 24 h), and further investigation demonstrated that M. mackini
      occurrence and infectivity severely declined following extracellular seawater
      incubation of more than 24 h. This study demonstrates a potential for using qPCR
      to monitor M. mackini in wild or farmed oyster populations during periods of
      disease remission or from environmental seawater samples. This work also suggests
      that gill tissues may provide a primary site for waterborne entry and possibly
      shedding of M. mackini in oysters. Further, although extracellular seawater
      transmission of M. mackini was possible, poor environmental stability and
      infection efficiency likely restricts the geographic transmission of M. mackini
      between oysters in natural environs and may help to explain localized areas of
      infection.

PMID- 29044045
TI  - Emergence of carp edema virus (CEV) and its significance to European common carp
      and koi Cyprinus carpio.
AB  - Carp edema virus disease (CEVD), also known as koi sleepy disease, is caused by a
      poxvirus associated with outbreaks of clinical disease in koi and common carp
      Cyprinus carpio. Originally characterised in Japan in the 1970s, international
      trade in koi has led to the spread of CEV, although the first recognised outbreak
      of the disease outside of Japan was not reported until 1996 in the USA. In
      Europe, the disease was first recognised in 2009 and, as detection and diagnosis
      have improved, more EU member states have reported CEV associated with disease
      outbreaks. Although the structure of the CEV genome is not yet elucidated,
      molecular epidemiology studies have suggested distinct geographical populations
      of CEV infecting both koi and common carp. Detection and identification of cases
      of CEVD in common carp were unreliable using the original PCR primers. New
      primers for conventional and quantitative PCR (qPCR) have been designed that
      improve detection, and their sequences are provided in this paper. The qPCR
      primers have successfully detected CEV DNA in archive material from
      investigations of unexplained carp mortalities conducted >15 yr ago. Improvement
      in disease management and control is possible, and the principles of biosecurity,
      good health management and disease surveillance, applied to koi herpesvirus
      disease, can be equally applied to CEVD. However, further research studies are
      needed to fill the knowledge gaps in the disease pathogenesis and epidemiology
      that, currently, prevent an accurate assessment of the likely impact of CEVD on
      European koi and common carp aquaculture and on wild carp stocks.

PMID- 29044046
TI  - Locally extensive meningoencephalitis caused by Miamiensis avidus (syn.
      Philasterides dicentrarchi) in a zebra shark.
AB  - Scuticociliatosis, caused by ciliated protozoa in the subclass Scuticociliatia of
      the phylum Ciliophora, can cause fatal disease in teleost fish species. However,
      information on scuticociliatosis in elasmobranchs is still scarce. In this
      report, we describe a case of locally extensive meningoencephalitis caused by
      Miamiensis avidus (syn. Philasterides dicentrarchi) in a 2 yr old captive zebra
      shark Stegostoma fasciatum. Granulocytic meningoencephalitis was observed through
      histological assessment. Inflammation was confined to the ventral aspect of the
      brain with a large number of ciliated protozoa, transforming into non-suppurative
      meningitis in the lateral aspect, and gradually vanished in the dorsal aspect. No
      histopathological and polymerase chain reaction (PCR) evidence of systemic
      dissemination of M. avidus was found. PCR targeting the gene coding the small
      subunit ribosomal RNA (SSUrRNA) of M. avidus was performed on the brain, liver,
      and gill tissues, and only brain tissue yielded a positive result. The DNA
      sequences from amplicons of the protozoal SSUrRNA gene were completely matched to
      that of M. avidus. The distribution of protozoa in the current case was mainly
      located in the brain and suggests the possibility of a direct neural invasive
      pathway of M. avidus through the nasal cavity/ampullary system and/or a unique
      tissue tropism of M. avidus specific to the brain in zebra sharks. Further
      investigations on the pathogenesis of M. avidus in elasmobranchs, especially
      zebra sharks, are needed.

PMID- 29044048
TI  - Proceedings of the seminar on comparative assessment of the environmental impact
      of radionuclides released during three major nuclear accidents: Kyshtym,
      Windscale, Chernobyl (October 1990).

PMID- 29044047
TI  - Scaling and the frequency dependence of Nyquist plot maxima of the electrical
      impedance of the human thigh.
AB  - OBJECTIVE: To define and elucidate the properties of reduced-variable Nyquist
      plots. APPROACH: Non-invasive measurements of the electrical impedance of the
      human thigh. A retrospective analysis of the electrical impedances of 154 normal
      subjects measured over the past decade shows that 'scaling' of the Nyquist plots
      for human thigh muscles is a property shared by healthy thigh musculature,
      irrespective of subject and the length of muscle segment. Here the term scaling
      signifies the near and sometimes 'perfect' coalescence of the separate X versus R
      plots into one 'reduced' Nyquist plot by the simple expedient of dividing R and X
      by X m , the value of X at the reactance maximum. To the extent allowed by noise
      levels one can say that there is one 'universal' reduced Nyquist plot for the
      thigh musculature of healthy subjects. MAIN RESULTS: There is one feature of the
      Nyquist curves which is not 'universal', however, namely the frequency f m at
      which the maximum in X is observed. That is found to vary from 10 to 100 kHz.
      depending on subject and segment length. Analysis shows, however, that the mean
      value of 1/f m is an accurately linear function of segment length, though there
      is a small subject-to-subject random element as well. Also, following the
      recovery of an otherwise healthy victim of ankle fracture demonstrates the clear
      superiority of measurements above about 800 kHz, where scaling is not observed,
      in contrast to measurements below about 400 kHz, where scaling is accurately
      obeyed. SIGNIFICANCE: The ubiquity of 'scaling' casts new light on the
      interpretation of impedance results as they are used in electrical impedance
      myography and bioelectric impedance analysis.

PMID- 29044049
TI  - Acute in vivo testing of a conformal polymer microelectrode array for multi
      region hippocampal recordings.
AB  - OBJECTIVE: The success of a cortical prosthetic device relies upon its ability to
      attain resolvable spikes from many neurons in particular neural networks over
      long periods of time. Traditionally, lifetimes of neural recordings are greatly
      limited by the body's immune response against the foreign implant which causes
      neuronal death and glial scarring. This immune reaction is posited to be
      exacerbated by micromotion between the implant, which is often rigid, and the
      surrounding, soft brain tissue, and attenuates the quality of recordings over
      time. APPROACH: In an attempt to minimize the foreign body response to a
      penetrating neural array that records from multiple brain regions, Parylene C, a
      flexible, biocompatible polymer was used as the substrate material for a
      functional, proof-of-concept neural array with a reduced elastic modulus. This
      probe array was designed and fabricated to have 64 electrodes positioned to match
      the anatomy of the rat hippocampus and allow for simultaneous recordings between
      two cell-body layers of interest. A dissolvable brace was used for deep-brain
      penetration of the flexible array. MAIN RESULTS: Arrays were electrochemically
      characterized at the benchtop, and a novel insertion technique that restricts
      acute insertion injury enabled accurate target placement of four, bare, flexible
      arrays to greater than 4 mm deep into the rat brain. Arrays were tested acutely
      and in vivo recordings taken intra-operatively reveal spikes in both targeted
      regions of the hippocampus with spike amplitudes and noise levels similar to
      those recorded with microwires. Histological staining of a sham array implanted
      for one month reveals limited astrocytic scarring and neuronal death around the
      implant. SIGNIFICANCE: This work represents one of the first examples of a
      penetrating polymer probe array that records from individual neurons in
      structures that lie deep within the brain.

PMID- 29044050
TI  - On atomic mechanisms governing the oxidation of Bi<sub>2</sub>Te<sub>3</sub>.
AB  - Oxidation of Bi2Te3 (space group R-3m) has been investigated using experimental
      and theoretical means. Based on calorimetry, x-ray photoelectron spectroscopy and
      thermodynamic modelling, Bi2Te3 is at equilibrium with Bi2O3 and TeO2, whereby
      the most stable compound is Bi2Te3, followed by Bi2O3. Hence, the reactivity of
      Bi towards oxygen is expected to be higher than that of Te. This notion is
      supported by density functional theory. The strongest bond is formed between Bi
      and Te, followed by Bi - O. This gives rise to unanticipated atomic processes.
      Dissociatively adsorbed oxygen diffuses through Bi and Te basal planes of
      Bi2Te3(0001) and preferably interacts with Bi. The Te termination considerably
      retards this process. These findings may clarify conflicting literature data. Any
      basal plane off-cut or Bi terminations trigger oxidation, but a perfect basal
      cleavage, where only Te terminations are exposed to air, may be stable for a
      longer period of time. These results are of relevance for applications in which
      surfaces are of key importance, such as nanostructured Bi2Te3 thermoelectric
      devices.

PMID- 29044051
TI  - Ocular surface squamous neoplasia: Are we calling a spade a spade?

PMID- 29044052
TI  - Management of nasolacrimal duct obstruction in children: How is it changing?

PMID- 29044053
TI  - Fungal keratitis: The Aravind experience.
AB  - Research becomes very significant and meaningful when it addresses a significant
      public health problem of a region. Fungal keratitis is a serious problem
      affecting the agrarian poor and hence requires attention from public health
      specialists. The approach to a public health issue should focus not only on
      treatment but also prevention or at least show a significant thrust to reduce the
      morbidity of the problem. At our institution, we have developed a special
      interest in fungal keratitis and tried to study it in a multitude of aspects. As
      we put the pieces of the puzzle together, we believe that interest will be
      rekindled among policymakers, clinicians, microbiologists, pharmaceutical
      industry, and basic scientists to work together to join forces and take up an
      integrative approach to managing this problem. It is also believed that the
      article underscores the need and importance of having a focused approach to
      ensuring a successful career in clinical research.

PMID- 29044054
TI  - Role of intravitreal/intracameral antibiotics to prevent traumatic
      endophthalmitis - Meta-analysis.
AB  - Traumatic endophthalmitis is a devastating condition that can occur following an
      open globe injury and result in loss of vision. The use of prophylactic
      antibiotics is empirical as most surgeons fear complications associated with the
      same. No systematic review has been performed in English on the role of
      intravitreal/intracameral antibiotics in preventing traumatic endophthalmitis. We
      searched for randomized controlled trials and controlled clinical trials
      comparing intracameral/intravitreal antibiotics with placebos on PubMed, Google
      Scholar, Science Direct, and Cochrane Library using keywords open
      globe/trauma/penetrating/perforating injuries endophthalmitis. The last search
      was on 5 May 2017. We included patients of all ages with open globe injuries who
      received intracameral/intravitreal antibiotics, regardless of the dose. Quality
      of the trials was assessed using Cochrane collaboration tools to assess the risk
      of bias. The main outcome measures were endophthalmitis and visual acuity. We
      included three trials. Overall, intravitreal/intracameral antibiotics were noted
      to significantly reduce the occurrence of endophthalmitis in open globe injuries
      (relative risk [RR] 0.19, 95% confidence interval [CI] 0.06-0.57). The use of
      intravitreal/intracameral antibiotics did not have an effect in improving visual
      acuity (RR 1.17, 95% CI 0.61-2.23). Two trials (Narang 2003; Soheilan 2001) were
      observed to have no significant effect on visual acuity while another trial
      (Soheilan 2007) did not list visual acuity as part of its objectives.
      Intracameral/intravitreal antibiotics reduce the risk of endophthalmitis in open
      globe injuries; although, there was no improvement in the visual acuity. We,
      therefore, recommend the use of intravitreal/intracameral injections in open
      globe injuries to prevent this devastating complication.

PMID- 29044055
TI  - Assessment of BicC family RNA binding protein 1 and Ras protein specific guanine
      nucleotide releasing factor 1 as candidate genes for high myopia: A case-control
      study.
AB  - PURPOSE: The aim is to evaluate the association between high myopia and genetic
      variant in the BicC family RNA binding protein 1 (BICC1) as well as its
      association with Ras protein specific guanine nucleotide releasing factor 1
      (RASGRF1) genes in a Chinese Han population with a case-control study. METHODS:
      Five TagSNPs in BICC1 and RASGRF1 genes were selected and genotyped in 821
      unrelated subjects, which composed of 419 controls (spherical equivalent within
      +/-1.00 D in both eyes and axial length ?24.0 mm) and 402 cases (spherical
      equivalent <=-6.0D in at least one eye and axial length >=26.0 mm). Statistical
      analysis was performed with SNPstats. RESULTS: After an analysis adjusted by age
      and sex, rs4245599 in BICC1 was found to be significantly associated with high
      myopia under the codominant, dominant, recessive and log-additive model (P =
      0.001, 0.0015, 0.0045 and 2e-04, odds ratio [OR] = 2.15, 1.59, 1.73 and 1.46,
      respectively), and rs10763559 in BICC1 was associated with high myopia and under
      the dominant and log-additive model (P = 0.032 and 0.036, OR = 0.72 and 0.78,
      respectively). Rs4778879 in RASGRF1 was found to be significantly associated with
      high myopia under codominant, dominant, recessive, and log-additive model (P =
      0.0088, 0.0065, 0.026, and 0.0021, OR = 1.87, 1.48, 1.56, and 1.37,
      respectively). However, no significant association was found between rs745030 in
      RASGRF1 and high myopia, neither was there any association of rs745029 in
      RASGRF1. CONCLUSION: The present study indicated that genetic variants in BICC1
      and RASGRF1 are closely associated with high myopia, which appears to be a
      potential candidate for high myopia in Chinese Han population. Considering the
      small sample size of this study, further work is needed to validate our results.
      The function of BICC1 and RASGRF1 in the process of developing high myopia needs
      to be explored in the future.

PMID- 29044056
TI  - Association of polymorphisms in the intron of TCF4 gene to late-onset Fuchs
      endothelial corneal dystrophy: An Indian cohort study.
AB  - PURPOSE: Fuchs endothelial corneal dystrophy (FECD) is a progressive degenerative
      disease of the corneal endothelium. It is genetically heterogeneous and follows
      either an autosomal dominant or sporadic pattern of inheritance. Here, we have
      explored the association of four previously reported intronic single nucleotide
      polymorphisms and intronic CTG repeat expansions in TCF4 gene to FECD in an
      Indian cohort. METHODS: The cohort consisting of 52 sporadic late-onset cases, 5
      early-onset cases, and 148 controls was taken for the study. rs2286812 and
      rs613872 were genotyped by allele specific polymerase chain reaction (ASPCR) and
      PCR-based restriction digestion, respectively; rs17595731 and rs9954153 were
      genotyped by Taqman assay using real-time PCR. The quantitative assessment of the
      CTG repeat region was performed by PCR/Sanger DNA sequencing. The repeats were
      assessed qualitatively by short tandem repeat and triplet repeat primed PCR
      assays. The statistical analysis was performed using two-tailed Fisher's exact
      probability test. RESULTS: SNPsrs613872 (G/T) for the 'G' allele (P value: 4.57 *
      10-5) and rs17595731 (C/T) for the 'C' allele (P value: 1.87 * 10-5),
      respectively, showed a significant association to sporadic late-onset FECD. CTG
      repeat expansions were found to be associated with FECD with a P value = 2.4 * 10
      3. CONCLUSION: rs613872, rs17595731, and CTG repeat expansions in intronic region
      of TCF4 are associated with increased risk of sporadic late-onset FECD in the
      Indian cohort studied.

PMID- 29044057
TI  - Clinicodemographic profile and treatment outcome in patients of ocular surface
      squamous neoplasia.
AB  - PURPOSE: The aim is to study the clinicodemographic profile and treatment outcome
      of ocular surface squamous neoplasia (OSSN). METHODS: This was a retrospective
      observational study of 57 eyes (56 cases) with clinically diagnosed OSSN,
      presenting in our center over the past year. RESULTS: The median age of
      presentation was 55 years with male:female ratio being 4.5:1. Systemic
      predisposing conditions were xeroderma pigmentosa (1) postkidney transplant
      immunosuppression (1), and human immunodeficiency virus infection (1). Patients
      with predisposing conditions had a younger median age of onset (33 years). The
      majority of tumors were nodular (61.4%), gelatinous (61.4%), and had limbal
      involvement (96%). On ultrasound biomicroscopy (UBM), mean tumor height was 2.93
      +/- 1.02 mm, and intraocular extension was evident in seven eyes. OSSN with
      intraocular extension had a mean tumor height of 4.3 +/- 1.32 mm. Nodal
      metastasis was seen in one case at presentation. As per American Joint Committee
      for Cancer Classification seventh edition staging-two cases were T1, one was T2,
      46 were T3 and eight were T4. Treatment advised included conservative therapy for
      39; wide local excision (4 mm margin clearance) with cryotherapy for seven;
      enucleation in four; and exenteration in four eyes. Overall, complete regression
      was achieved in 88% of cases during a mean follow-up of 13.5 +/- 4.6 months.
      Recurrence was seen in three cases, which were treated with exenteration, radical
      neck dissection, and palliative chemo-radiotherapy, respectively. CONCLUSION:
      Although associated with old age, earlier onset of OSSN is seen in patients with
      systemic predisposing conditions. Thicker tumors in the setting of a previous
      surgery or immunocompromised status should be considered high-risk features for
      intraocular extension and should be evaluated on UBM.

PMID- 29044058
TI  - Femtosecond laser-assisted cataract surgery versus 2.2 mm clear corneal
      phacoemulsification.
AB  - PURPOSE: Phacoemulsification is the surgical procedure of choice for cataract,
      providing excellent visual and safety outcomes. Femtosecond laser-assisted
      cataract surgery (FLACS) is an addition to the surgical armamentarium. The study
      aims to compare the outcomes of FLACS using LenSxTM (Alcon Inc., USA) to standard
      2.2 mm clear corneal phacoemulsification. Prospective case-control, comparative,
      interventional study was conducted in a tertiary care center. METHODS: In each
      group, 55 eyes of 55 patients underwent cataract surgery using either FLACS or
      conventional phacoemulsification (control group). The primary outcome variables,
      uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), specular
      microscopy, pachymetry, mean absolute error (MAE), and anterior chamber depth
      (ACD) were compared between two groups at 4 weeks postoperatively. Intraoperative
      effective phaco time (EPT), postoperative circularity of the rhexis, capsular
      overlap over the edge of the intraocular lens (IOL), and decentration of the IOL
      were the secondary variables which were compared. RESULTS: No significant
      difference was found between the groups for UCVA, pachymetry, MAE, and ACD at 4
      weeks postoperatively. The FLACS group had better BCVA (P = 0.0294). Circularity
      of capsulorrhexis (P = 0), circular overlap over the edge of IOL (P = 0), and
      centration of IOL (P = 0.002) at 4 weeks postoperatively were better in the FLACS
      group. EPT was lower in FLACS for similar grade of cataract (P = 0). Endothelial
      cell loss in FLACS group was 4.2% more (P = 0.032). CONCLUSIONS: FLACS is
      superior to conventional phaco in the circularity of rhexis, capsular overlap,
      and centration of the IOL and uses less EPT. However, conventional
      phacoemulsification is equivalent to FLACS in most other parameters.

PMID- 29044059
TI  - Pathology and immunohistochemistry of capsular bag in spontaneously late
      dislocated capsular bag-intraocular lens complex.
AB  - PURPOSE: Our study aims to evaluate the morphology, histopathology, and
      immunohistochemistry of the spontaneously late dislocated capsular bag
      intraocular lens (CB-IOL) complex. Various etiologies and possible pathogenesis
      of the event are also discussed. METHODS: This was a tertiary-care setting and
      retrospective observational case series. The surgically explanted intact
      specimens of spontaneously late dislocated CB-IOL complex were studied. The
      demographics, duration of pseudophakia, IOL design/material, and specimen
      measurements were noted. Fresh specimens were photographed, and computer software
      was used for measurements. After processing, a detailed microscopic examination
      was carried out for three different sections of each specimen with hematoxylin
      and eosin (H and E), Masson's-trichrome, and immunohistochemistry stain for
      vimentin. The Mann-Whitney U-test was used for the statistical analysis. RESULTS:
      Of 12 specimens, the mean CB and capsulorhexis opening size were 8.32 +/- 0.8 mm
      and 3.62 +/- 0.61 mm, respectively. The average CB-IOL complex size of our study
      was significantly lower than the studies reported in the literature (P <= 0.001).
      All (n = 12, 100%) were acrylic IOLs with 11 (91.67%) having single-piece design.
      All specimens on H and E stain showed extensive subepithelial fibrosis while
      Masson's trichrome staining showed that none had any pseudoexfoliation material.
      The circumferential sphincter-like fibrous tissue arrangement was seen in all
      specimens. Immunohistochemical expression of vimentin suggested the mesenchymal
      metaplasia of epithelial A-cells. CONCLUSION: Significant fibrotic contraction of
      the CB and phimosis of capsulorhexis may cause a progressive zonular tear. This
      is probably the most important etiology of spontaneous late dislocation of the CB
      IOL complex.

PMID- 29044060
TI  - Interocular symmetry of retinal nerve fiber layer and optic nerve head parameters
      measured by Cirrus high-definition optical coherence tomography in a normal
      pediatric population.
AB  - PURPOSE: To determine interocular differences in the retinal nerve fiber layer
      (RNFL) and optic nerve head (ONH) parameters in a pediatric population using
      Cirrus high-definition optical coherence tomography (HD-OCT). METHODS: Seventy
      normal Indian children aged 5-17 years presenting to the Pediatric Clinic were
      included in this observational cross-sectional study. All subjects underwent a
      comprehensive ophthalmologic examination and an evaluation of the RNFL and ONH by
      Cirrus HD-OCT. Differences between the right and left eyes were calculated and
      values were compared by means of a paired t-test. Subjects were also divided into
      two groups based on age (under or over 10 years of age). Interocular differences
      in RNFL and ONH parameters together with sex and age variations for these
      differences were determined. RESULTS: The mean age of studied pediatric
      population was 11.83 +/- 3.3 years (range 5-17). Average RNFL thickness was 94.46
      +/- 8.7 MUm (+/- SD) (range 77-111). Differences in the average RNFL between
      right and left eyes were not statistically significant (P = 0.060). Superior
      quadrant RNFL was thicker in the left eye and temporal quadrant was thicker in
      the right eye. Among ONH parameters, there were no statistically significant
      differences in any parameters, except vertical cup-disc (CD) ratio which was
      significant (P = 0.007). The 2.5%-97.5% limits of asymmetry were 9 MUm for
      average RNFL, 0.14 for average CD ratio, and 0.22 for vertical CD ratio. Mean
      interocular RNFL thickness differences in superior, superior nasal, and temporal
      superior quadrants were 10.61 (P < 0.001), 12.57 (P < 0.001), and 4.46 (P =
      0.002) MUm, respectively. Interocular nerve fiber layer thickness differences
      were not significantly correlated with sex, while only significant differences
      with age were observed in 12 clock hour sector analysis, mainly in nasal inferior
      and inferior quadrant. CONCLUSIONS: We report the degree of interocular symmetry
      of RNFL and ONH parameters measured by Cirrus HD-OCT in a healthy pediatric
      population. The normal interocular RNFL asymmetry should not exceed 9 MUm and
      vertical CD ratio beyond 0.22 should be considered for further investigations.
      The physiologic asymmetry provided by this study may assist in identifying
      changes in RNFL thickness and ONH parameters in pediatric glaucoma and ONH
      disorders.

PMID- 29044061
TI  - Long-term scanning laser ophthalmoscopy and perimetry in different severities of
      primary open and chronic angle closure glaucoma eyes.
AB  - PURPOSE: To determine rate of change over time on scanning laser ophthalmoscopy,
      HRT, compared to perimetry, and to determine incidence, parametric changes, and
      risk factors for progression in primary open angle glaucoma (POAG) and chronic
      primary angle closure angle glaucoma (CPACG) eyes. METHODS: Prospective clinical
      study of 116 POAG eyes and 129 CPACG eyes of different severities of glaucoma.
      Standard automated perimetry and optic nerve head topography were studied at
      baseline and thereafter every 6 months. Changes in HFA and HRT parameters, in
      response to IOP, were compared over at least 5 years. RESULTS: Fourteen POAG eyes
      (12.1%) and 20 CPACG eyes (15.5%) showed progression on SAP over time. Percentage
      drop of IOP was similar in eyes that progressed and in stable eyes. The change in
      MD in CPACG eyes was 1.8 dB/year on SAP and 1.36 dB/year in POAG eyes, P = 0.1.
      Twenty-nine eyes showed progression on HRT with 24 confirmed on SAP. Trend
      analysis picked up progression more frequently than other HRT parameters. Eyes
      that progressed in both groups, in all severities of glaucoma, had intermittent
      fluctuations of >= 4 mmHg over mean IOP on >=3 follow up visits, P <= 0.001.
      CONCLUSION: IOP fluctuations of >= 4 mmHg over the mean IOP and duration of
      disease were associated with progression in POAG and CPACG eyes.

PMID- 29044062
TI  - Changing epidemiology of neovascular glaucoma from 2002 to 2012 at King Khaled
      Eye Specialist Hospital, Saudi Arabia.
AB  - PURPOSE: The aim is to present the incidence and determinants of neovascular
      glaucoma (NVG) in Saudi Arabia. METHODS: A retrospective review of NVG cases
      (2002-2012) was included to estimate the incidence. The determinants included
      gender, age, comorbidities, lens status, type of NVG, and visual acuity on
      presentation. The impact of antiangiogenic therapy on NVG incidence was studied.
      RESULTS: We studied 597 eyes with NVG. The incidence was 6.6/10,000. It declined
      from 13/10,000 in 2008-0.1/10,000 in 2012 (P < 0.001). The decline in 2008
      coincided with the introduction of intravitreal injection bevacizumab in Saudi
      Arabia. Males had a significantly higher NVG risk (odds ratio [OR] = 2.2).
      Diabetes and hypertension were associated with NVG in 88% and 42.7% of cases,
      respectively. In 377 (72%) diabetic patients, the glycemic control was poor
      (HbA1C >7%). Visual acuity was 20/20-20/40 in 14 (2%), 20/50-20/200 in 79 (13%),
      20/200-20/400 in 456 (76%), and <20/400 in 45 (7%) eyes. Intraocular pressure was
      higher than 30 mmHg in 438 (73%) eyes. The cup-to-disc (CD) ratio was >0.8 in 86
      (14%) eyes. During the early period (2002-2007) and later period (2008-2012), CD
      ratio (chi2 = 4, P = 0.09) and anterior chamber angle (P = 0.8) were not
      different. The presence of NVG in contralateral eye (OR = 0.8, P = 0.3) in both
      periods was similar. CONCLUSIONS: NVG was associated with diabetes in a very
      large proportion of patients. It was significantly associated with males, and
      with poor glycemic control and poor vision at presentation. The incidence of NVG
      declined after the introduction of intravitreal bevacizumab.

PMID- 29044063
TI  - Cognitive functions and normal tension glaucoma.
AB  - PURPOSE: Only a few studies have analyzed the potential link between glaucoma and
      cognitive function impairment. They have found controversial results. This study
      aims to perform quick cognitive function assessment with clock drawing test (CDT)
      using two different scoring systems and compare between normal tension glaucoma
      (NTG) and cataract patients. METHODS: Totally, 30 NTG and 30 patients with
      cataracts were included in a prospective, pilot study. The predrawn circle was
      given, and patients were asked to draw the clock showing a time of 11:10. The
      test was evaluated using two methods - Freund method using a 7-point scoring
      scale (optimal cutoff <=4) and Rakusa using a 4-point scoring scale (optimal
      cutoff <=3). The level of significance was set at P < 0.05. RESULTS: CDT result
      was significantly better in cataract group than in NTG group: 3.5 (2) versus 2
      (2) by Freund, (P = 0.003) and 6.5 (1) versus 4.5 (2.75) by Rakusa, respectively
      (P = 0.004). Sixty percent (n = 18) of NTG group and 10% (n = 3) of cataract
      group patients completed the CDT in the specific picture manner (the short hand
      on 11 and the long hand between 11 and 12), (P = 0.001). CONCLUSIONS: Lower CDT
      results were seen in NTG patients according to two different scoring systems. NTG
      patients showed a specific manner of drawing. Further prospective studies are
      needed to investigate the CDT reliability as fast screening test of cognitive
      function impairment in glaucoma patients.

PMID- 29044064
TI  - Utility of angiotensin-converting enzyme activity in aqueous humor in the
      diagnosis of ocular sarcoidosis.
AB  - PURPOSE: Many studies include elevated activity of angiotensin-converting enzyme
      (ACE) in serum in sarcoidosis and in ocular sarcoidosis as well, but there are
      only a few analyzing ACE activities in aqueous humor. The aim of this study is to
      illuminate the diagnostic value of ACE in aqueous humor in patients with ocular
      sarcoidosis. METHODS: We analyzed twenty patients with ocular sarcoidosis and 18
      patients with nonocular involvement. All patients have biopsy-positive
      sarcoidosis of the lungs and/or mediastinal lymph nodes. Blood samples for ACE
      serum levels were obtained from all patients. Aqueous humor samples were taken by
      paracentesis with a 25-gauge needle in local anesthesia. With appropriate
      statistical tests, we compared ACE activity in serum and aqueous humor in
      patients with and without ocular sarcoidosis. RESULTS: The majority of our
      patients with ocular sarcoidosis were female (12/20), also in the group with
      systemic sarcoidosis and without ocular involvement (12/6). Mean age of the whole
      analyzed group of sarcoidosis patients was 45 +/- 6 years. There is no
      statistically significant difference in ACE activity in serum between two groups
      of patients (with and without ocular sarcoidosis). There is statistically
      significant difference in ACE activity in aqueous humor among patients with
      ocular and nonocular sarcoidosis. ACE activity in aqueous humor is significantly
      higher in patients with ocular sarcoidosis. CONCLUSION: Increased ACE activity in
      aqueous humor can point to a diagnosis of ocular sarcoidosis, without the need
      for ocular biopsy.

PMID- 29044065
TI  - The adverse effects of valproic acid on visual functions in the treatment of
      retinitis pigmentosa.
AB  - PURPOSE: To evaluate the efficacy and safety of valproic acid (VPA) treatment in
      patients with retinitis pigmentosa (RP). METHODS: A total of 48 eyes of 24
      patients (13 males, 11 females) with RP prescribed VPA were included. The length
      of VPA treatment was 6-12 months (mean 9.4 months). Parameters evaluated were
      best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution
      [logMAR]), visual field analyses (VFAs) with Humprey automated perimetry,
      multifocal electroretinography (ERG) with Roland-RETI scan, and VPA side effects.
      RESULTS: Mean age was 34.3 +/- 10.3 years (range 18-56 years). Fifteen of the
      patients (30 eyes) had two ERG and VFA tracings, allowing comparison between
      baseline and follow-up (range 6-12 months). Mean BCVA before and after VPA
      therapy was 0.36 +/- 0.38 and 0.36 +/- 0.37 logMAR, respectively (P = 0.32).
      Quantitative perimetric indices including mean deviation and pattern standard
      deviation were not significantly changed after VPA therapy (P > 0.05). P1
      amplitudes (in terms of nV/deg2 and mV) of ERG waves were significantly decreased
      in the rings 1, 3, and 4 after VPA therapy (P < 0.05). Regarding the N1
      amplitudes, the only significant decrease was observed in area 1 (P = 0.03). In
      addition, N1 latency was significantly increased in area 3 after VPA therapy (P =
      0.04). CONCLUSIONS: VPA therapy did not have any significant benefit on BCVA and
      VFA. In addition, it may be associated with decline in some ERG parameters.
      Therefore, physicians should avoid prescribing VPA for RP until its safety and
      efficacy are appropriately evaluated.

PMID- 29044066
TI  - Color vision abnormalities in type II diabetes: Sankara Nethralaya Diabetic
      Retinopathy Epidemiology and Molecular Genetics Study II report no 2.
AB  - PURPOSE: The purpose of this study is to assess color vision abnormalities in a
      cohort of subjects with type II diabetes and elucidate associated risk factors.
      METHODS: Subjects were recruited from follow-up cohort of Sankara Nethralaya
      Diabetic Retinopathy Epidemiology and Molecular Genetics Study I. Six hundred and
      seventy-three eyes of 343 subjects were included from this population-based
      study. All subjects underwent detailed ophthalmic evaluation, including the
      Farnsworth-Munsell 100 hue test. RESULTS: The prevalence of impaired color vision
      (ICV) was 43% (CI: 39.2-46.7). Risk factors for ICV were higher heart rate (odds
      ratio [OR]: 1.043, [1.023-1.064]) and a higher intraocular pressure (IOP) (OR:
      1.086, [1.012-1.165]). Subjects with clinically significant macular edema (CSME)
      had three times higher chance of having ICV. C1, C2, and C3 are the commonly
      found Early Treatment Diabetic Retinopathy Study (ETDRS) patterns. The moment of
      inertia method showed that the angle did not reveal any specific pattern of color
      vision defect. Although the major and minor radii were high in those with ICV, we
      did not observe polarity. Confusion index was high in subjects with ICV,
      indicating a severe color vision defect. CONCLUSIONS: The prevalence of ICV was
      43% among subjects with type II diabetes. The most commonly observed patterns
      were increasing severities of the blue-yellow defect on ETDRS patterns, but no
      specific pattern was observed at the moment of inertia analysis. The presence of
      CSME, a higher heart rate, and IOP was significant risk factors for ICV. This
      functional impairment in color vision could significantly contribute to morbidity
      among subjects with diabetes.

PMID- 29044067
TI  - Improvement in distance and near visual acuities using low vision devices in
      diabetic retinopathy.
AB  - PURPOSE: The aim of this study is to elucidate the causes and level of visual
      impairment (VI) in patients with different pathologies of diabetic retinopathy
      (DR) who presented to a low vision care (LVC) clinic, to analyze the type of
      distant and near devices prescribed to them and the visual benefits thereof.
      METHODS: A retrospective chart review was done for 100 consecutive patients with
      DR who were referred to the LVC clinic from June 2015 to June 2016. The reason
      for referral was assessed from the electronic medical records and available
      fundus photographs, fundus fluorescein angiograms, and optical coherence
      tomography images by a retina specialist. The details of low-vision devices and
      subsequent improvements were noted. RESULTS: Of the 100 patients, 52% had
      moderate VI, 19% mild VI, 16% severe VI, and 13% had profound VI or blindness.
      The most commonly prescribed low vision device was half-eye spectacles (38.4%).
      The pathologies which had statistically significant improvement (P < 0.05) in
      distance vision with low vision devices were DR with disc pallor (4.4%
      improvement), ischemic maculopathy (11.9% improvement), and plaque of hard
      exudate (10.1% improvement). However, in all pathologies, there was statistically
      significant improvement (P < 0.05) in near vision. CONCLUSION: Usually, the
      patients with DR presented to the LVC clinic with moderate VI. The use of low
      vision devices can help these patients in cases where medical and surgical
      treatment have no or a limited role in restoring useful vision.

PMID- 29044068
TI  - Needle stick injuries in a tertiary eye-care hospital: Incidence, management,
      outcomes, and recommendations.
AB  - PURPOSE: The purpose of this study is to assess the incidence, management, and
      outcomes for needle stick injuries (NSIs) in a tertiary eye-care hospital and
      provide appropriate recommendations for its prevention. METHODS: This was a
      retrospective database review of NSI recorded between 2010 and 2015 at a tertiary
      eye care center. All staff members who had NSI were managed with standard
      treatment protocol. The mode, location, health-care workers affected and/or at
      risk for NSI were analyzed. RESULTS: One hundred and forty NSI were reported
      between 2010 and 2015, with ophthalmic fellows under training encountering
      maximum needle pricks (n = 33; 24%), followed by nursing staff (n = 32; 23%), and
      consultants (n = 30; 21%). Location wise, the highest incidence of NSI was found
      in the operating room (n = 94; 67%), followed by the laboratory (n = 17; 12%),
      and patients' ward (n = 14; 10%). Maximum pricks (n = 10; 20%) occurred while
      passing sharp instruments, anterior segment surgeons (n = 23; 79%) being affected
      more than posterior segment surgeons (n = 6; 21%). None of the NSI incidents was
      attributed to anti-VEGF injections. None of the subjects with NSI had
      seroconversion to hepatitis B surface antigen, human immunodeficiency virus, or
      hepatitis C virus in the 5-year study period. CONCLUSIONS: NSI is the most
      commonly encountered in the operating room among training personnel while passing
      sharp instruments, especially anterior segment surgeons. A proper needle/sharp
      disposal mechanism, documentation of adverse event, on-going staff training, and
      prompt prophylactic treatment are essential components of the protocol for NSI
      management.

PMID- 29044069
TI  - Primary nonendoscopic endonasal versus external dacryocystorhinostomy in
      nasolacrimal duct obstruction in children.
AB  - PURPOSE: The aim is to compare the outcome of nonendoscopic endonasal
      dacryocystorhinostomy (NEN DCR) with external DCR (EXT-DCR) in the treatment of
      nasolacrimal duct obstruction (NLDO) in children. METHODS: A retrospective,
      comparative chart analysis of all consecutive children <16 years after EXT-DCR or
      NEN-DCR between June 2012 and February 2016. RESULTS: Seventy-one children (79
      eyes) underwent DCR in the study, of which 37 children (40 eyes) underwent EXT
      DCR and 34 (39 eyes) NEN-DCR. Mean age of both groups (8.7 vs. 7.7 years) was
      comparable. Etiologically, persistent congenital NLDO was the most common
      indication (50% vs. 72%), followed by acquired and secondary NLDO. Mean duration
      was shorter for NEN-DCR (47 vs. 37 min; P = 0.0021). Mitomycin C 0.04% was used
      more often in NEN-DCR (10% vs. 56.41%). Success after primary EXT-DCR was 100% as
      compared to 75% for primary NEN-DCR at median follow-up of 12 and 16 months
      respectively. At revision, the main cause of failure was granuloma (60%). After
      revision, all eyes were symptom-free at a median follow-up of 9.5 months.
      CONCLUSION: Primary NEN-DCR has a poorer outcome than EXT-DCR in the treatment of
      NLDO in children and is more likely to need a revision procedure.

PMID- 29044070
TI  - Pediatric dacryocystorhinostomy.

PMID- 29044071
TI  - Prevalence of spheroidal degeneration of cornea and its association with other
      eye diseases in tribes of Western Rajasthan.
AB  - PURPOSE: To determine the prevalence of spheroidal degeneration of cornea (SDC)
      and its association with other eye diseases in the tribes of South-West
      Rajasthan. METHODS: A total of 5012 patients were examined on slit lamp for the
      diagnosis of SDC. Diagnosis of SDC was made based on presence of amber granules
      in the superficial stroma of peripheral interpalpebral cornea with increasing
      opacification, coalescence and central spread or nodular and hazy surrounding
      stroma and divided in three stages. RESULTS: The prevalence of SDC was 10.7%.
      Around 55% of the total of 535 cases examined were found to have Stage I followed
      by Stage II (32%) and Stage III (13%). The prevalence is greatest in both men and
      women over 70 years of age. The severity of SDC is greater in men. SDC was
      significantly associated with pterygium and pseudocapsular exfoliation.
      CONCLUSION: Extreme temperature, low humidity, dust, high wind, and microtrauma
      caused by sand particles are the probable etiologies for higher prevalence of
      this kind of degeneration in this region.

PMID- 29044072
TI  - Novel technique of smartphone-based high magnification imaging of the eyelid
      lesions.

PMID- 29044073
TI  - Type 2 big bubble deep anterior lamellar keratoplasty-serial anterior segment
      optical coherence tomography documentation showing resolution of bubble in the
      postoperative period.

PMID- 29044074
TI  - Anterior capsule rupture: Does this ring, ring a bell?

PMID- 29044075
TI  - Fundus autofluorescence imaging of subinternal limiting membrane hemorrhage in
      anemic retinopathy.

PMID- 29044076
TI  - Vitreous opacities causing artifacts in optical coherence tomography angiography.

PMID- 29044077
TI  - Ophthalmic manifestations in Rothmund-Thomson syndrome: Case report and review of
      literature.
AB  - A 24-year-old male patient presented to us with diminution of vision in both eyes
      with watering and photophobia for the past 8 years. General physical examination
      showed short stature and poikiloderma. Ocular findings include photophobia with
      reflex tearing, dry eye, cicatricial ectropion, symblepharon approaching
      pupillary area of cornea, and multiple superficial punctuate erosions on the
      cornea. Both eyelids showed scanty meibomian glands on infrared meibography. The
      rest of the anterior and posterior segment was normal. The patient was treated
      with topical lubricants which reduced photophobia and corneal erosions. He then
      underwent symblepharon release with buccal mucosal grafting, which improved
      ectropion. Patient improved symptomatically with reduction of photophobia and
      improvement in vision as well.

PMID- 29044078
TI  - Primary calcareous degeneration of the cornea.
AB  - Primary calcareous degeneration is a rare corneal disease. In the past 50 years,
      only four cases have been described. We present the case of a 26-year-old male
      patient with progressive calcium deposition in both eyes with negative laboratory
      parameters. For the first time, anterior segment optic coherence tomography was
      used to investigate and establish the proper treatment.

PMID- 29044079
TI  - Ultrasonographic evaluation of transition from normal to ectatic area: A
      comparison between myopic staphylomata and coloboma.
AB  - Choroidal coloboma and posterior staphyloma are two clinically distinct entities,
      with choroidal excavation being a unifying feature. They are associated with
      early onset cataract which can make ophthalmoscopy difficult. This report studies
      the transition between the normal and ectatic area in these cases with
      ultrasound. We evaluate "posterior hump" as a sign of differentiation between
      these two conditions.

PMID- 29044080
TI  - Amalric sign: An augur of ophthalmic artery occlusion.
AB  - A 75-year-old man presented to us with sudden onset of profound vision loss in
      his right eye and was identified as suffering from an ophthalmic artery
      occlusion. Apart from the retinal whitening and box-carring of the retinal
      arteries, there were characteristic triangular patches of retinal whitening in
      the midperipheral temporal fundus indicating a previous lateral posterior
      choroidal artery occlusion. The patient was a chronic smoker and had
      dyslipidemia. The carotid Doppler study showed complete occlusion of the internal
      carotid artery. The presence of these triangular patches of retinal whitening or
      amalric sign can therefore herald a more proximal vessel occlusion. Hence such
      patients require evaluation on an emergency basis. The characteristic features of
      the patches on fluorescein angiography and indocyanine green angiography are
      discussed here.

PMID- 29044081
TI  - Retained intraocular iron foreign body presenting with acute retinal necrosis.
AB  - We report an unusual case of retained metallic intraocular foreign body (IOFB)
      presenting with acute retinal necrosis (ARN). A healthy young man presented with
      signs of ARN including hypopyon, dense vitritis, and peripheral retinal necrosis
      following alleged history of trauma with a high-velocity projectile. After
      initial management of ARN with systemic antivirals, a retained metallic IOFB was
      identified and subsequently removed surgically. The patient was followed up for
      12 months postoperatively and retained excellent vision without recurrence of the
      ARN. The diagnosis of an IOFB in a case with associated inflammation can be
      challenging. A strong clinical suspicion with proper investigations can achieve
      optimum results.

PMID- 29044082
TI  - Rickettsial retinitis: Direct bacterial infection or an immune-mediated response?
AB  - Infectious retinitis postfebrile illness is known to be caused by chikungunya,
      dengue, West Nile virus, Bartonella, Lyme's disease, Rift Valley fever,
      rickettsia, Herpes viruses etc. Rickettsia is Gram-negative bacteria transmitted
      by arthropods vectors. Ocular involvement is common including conjunctivitis,
      keratitis, anterior uveitis, panuveitis, retinitis, retinal vascular changes, and
      optic nerve involvement. Retinitis lesions in rickettsia can occur because of an
      immunological response to the bacteria or because of direct invasion and
      proliferation of bacteria in the inner retina. We report such a case of bilateral
      rickettsial retinitis proven by serology which worsened on systemic steroids and
      responded dramatically to therapy with oral doxycycline and steroid taper. We
      thus believe that direct bacterial invasion plays a major role in the
      pathogenesis of rickettsial retinitis.

PMID- 29044083
TI  - Commentary: Rickettsial retinitis - Direct bacterial infection or an immune
      mediated response?

PMID- 29044084
TI  - Infectious chorioretinitis in an immunocompetent patient: A diagnostic dilemma.
AB  - A 44-year-old male presented with a history of defective vision in the right eye
      for the past 5 months with the previous history of tubercular cervical
      lymphadenitis. On examination, right eye revealed panuveitis with dense vitritis
      and chorioretinitis in the superotemporal quadrant. His Mantoux test was positive
      (25 mm * 25 mm induration), QuantiFERON-TB Gold was test positive, aqueous
      aspirate was positive for Mycobacterium tuberculosis genome, negative for viruses
      and toxoplasma, and hence he was initiated on four-drug antitubercular therapy
      (ATT) with oral steroids. On follow-up, he had worsening of vitritis and
      intravenous methylprednisolone was given suspecting paradoxical reaction to ATT;
      however, a repeat AC tap was positive for toxoplasma B1 genome, IgG
      antitoxoplasma antibody was also positive in serum and aqueous; hence, we
      switched to systemic antitoxoplasma therapy. He underwent a therapeutic
      vitrectomy along with intravitreal clindamycin and dexamethasone for persistent
      vitreous membranes and vitritis. The patient responded well to the treatment with
      a reduction in vitritis and scarring of the lesion.

PMID- 29044085
TI  - Vitrectomy for epiretinal membrane in adult-onset Coats' disease.
AB  - Coats' disease is characterized by retinal vascular telangiectasia and subretinal
      and intraretinal exudation. A relatively benign form of the disease that occurs
      in adults is referred to as adult-onset Coats' disease. Involvement of macula in
      the form of macular edema and exudation are the common presenting features in
      both forms of the disease. We describe a rare case of adult-onset Coats' disease
      that presented with epiretinal membrane (ERM). Laser photocoagulation of retinal
      vascular telangiectasia resulted in worsening of patient's symptoms and ERM.
      Early pars plana vitrectomy resulted in resolution of the patient's symptoms.
      Utility of ultra-wide-field imaging and rationale of early vitrectomy in such
      cases are discussed.

PMID- 29044086
TI  - Optical coherence tomography angiography of circumscribed choroidal hemangioma
      treated with photodynamic therapy.
AB  - We describe features of a circumscribed choroidal hemangioma (CCH) treated with
      photodynamic therapy (PDT) by means of optical coherence tomography angiography
      (OCT-A). A 40-year-old man had a complaint of decreasing visual acuity in his
      left eye for 10 days. A diagnosis of CCH was confirmed by fundus examination,
      fluorescein angiography, and indocyanine green angiography. An OCT-A study of
      choroidal lesion before and after PDT was carried out. Segmented en face OCT-A of
      CCH showed multiple irregular connected vascular channels with hyperflow and a
      capillary-like lesion. Absent and/or reduced intrachannel flow in most of the
      intratumoral vessels was shown by OCT-A soon after treatment (2 days), with
      normalization of vascular flow 7 days and 1 month after PDT. OCT-A was able to
      noninvasively visualize intrinsic vasculature of CCH showing vascular remodeling
      after PDT.

PMID- 29044087
TI  - Bilateral disc drusen in a diabetic patient simulating diabetic papillopathy as a
      cause of disc edema.
AB  - Bilateral optic disc edema in a diabetic patient may be caused by diabetic
      papillopathy. We herein report on a patient with bilateral optic disc drusen
      simulating diabetic papillopathy. A 55-year-old patient with type 2 diabetes
      presented with decreased vision of 1-month. Diabetic papillopathy was initially
      considered as there was disc edema in both eyes with focal hemorrhages at the
      disc margin and mild visual loss. Ultrasound of the optic nerve head revealed
      optic disc drusen in both eyes and this was also confirmed by the control
      photograph. Optic nerve head drusen should be considered in the differential
      diagnosis of a diabetic patient presenting with disc edema.

PMID- 29044088
TI  - Management of idiopathic intracranial hypertension in an infant with bilateral
      congenital cataract and associated comitant sensory esotropia.
AB  - In this report, we describe the management of a child with bilateral cataract,
      nystagmus, and comitant sensory esotropia. Routine ultrasonography done before
      cataract surgery revealed bilateral disc edema confirmed as idiopathic
      intracranial hypertension by a pediatric neurologist. The primary intervention
      for cataract surgery was followed by nonresolving papilledema, despite maximum
      medical therapy. To salvage the optic nerve function in a nonverbal child,
      bilateral optic nerve sheath decompression was planned with simultaneous medial
      rectus recessions for the persistent esotropia with the satisfactory
      postoperative outcome.

PMID- 29044089
TI  - Congenital sixth nerve palsy with associated anomalies.
AB  - Congenital abduction deficit is most likely due to Duane's retraction syndrome as
      congenital abducens nerve palsy is very rare. We report two cases of infantile
      abduction deficit due to sixth nerve palsy associated with other anomalies to
      highlight the importance of including neuroimaging in the evaluation of an infant
      presenting with a limitation of abduction.

PMID- 29044090
TI  - Contralateral eye surgery with adjustable suture for management of third nerve
      palsy with aberrant regeneration.
AB  - Aberrant regeneration of the third nerve following its palsy is commonly seen
      after trauma and compressive lesions. This phenomenon is thought to result due to
      misdirection of the regenerating axons. Surgical management is a great challenge
      in the third nerve palsy owing to multiple muscle involvement and is often
      accompanied by ptosis and poor Bell's phenomenon. We present a case of a 27-year
      old male who developed isolated complete third nerve palsy of the left eye
      following head trauma. Features of aberrant regeneration were seen after 6
      months, namely, inverse Duane's sign and Pseudo-Von Graefe's sign. He underwent
      recess-resect procedure in the unaffected eye with adjustable suture technique
      which not only corrected the deviation but also the ptosis by utilizing the
      oculomotor synkinesis. Thus, contralateral eye surgery combined with adjustable
      suture technique resulted in an accurate alignment of the eye and obviated the
      need for ptosis correction.

PMID- 29044091
TI  - Management of a case of divergent strabismus fixus secondary to a congenital
      fibrosis of extraocular muscles type 2.
AB  - A 17-year-old boy presented with a large exotropia with both eyes fixed in an
      abduction and upgaze, pupillary involvement since childhood. He had mild optic
      nerve hypoplasia in the right eye and situs inversus of the retinal vessels in
      the left optic disc. His ocular motility showed restriction of eye movements in
      all gazes. He was diagnosed with congenital fibrosis of extraocular muscles, type
      2 (CFEOM2) and operated upon in a staged procedure with a satisfactory eye
      alignment using hang-back sutures in one eye and periosteal fixation in the
      other. This report highlights the surgical course and final outcome in this case
      of CFEOM2.

PMID- 29044092
TI  - Isolated nonpulsatile enophthalmos in neurofibromatosis: An uncommon entity.
AB  - Isolated enophthalmos is a rarely observed entity in neurofibromatosis (NF). A 12
      year-old male presented with right lower eyelid fat prolapse and enophthalmos for
      the past 7 years. There was no history of antecedent trauma/surgery. Computed
      tomography of orbit revealed an ill-defined intraconal hyperdense lesion located
      between lateral and inferior rectus along with an enlarged inferior orbital
      fissure (IOF). Superior orbital fissure was minimally widened without prolapse of
      any intracranial contents. Excision biopsy along with repair of widened IOF was
      performed through inferior transconjunctival route. Histopathology was suggestive
      of plexiform neurofibroma with positivity for S-100 and epithelial membrane
      antigen. No associated cutaneous lesions were present. Nonpulsatile enophthalmos
      with eyelid fat prolapse can be a presenting sign of NF.

PMID- 29044093
TI  - Erratum: Variation in the vitreoretinal configuration of Stage 4 retinopathy of
      prematurity in photocoagulated and treatment naive eyes undergoing vitrectomy.
AB  - [This corrects the article DOI: 10.4103/ijo.IJO_1_17.].

PMID- 29044094
TI  - Evaluation of Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio in patients with
      mitral valve stenosis before and after balloon valvuloplasty.
AB  - OBJECTIVE: Sympathetic activity increases in patients with mitral stenosis (MS).
      The association between prolonged Tpeak-Tend (Tp-e) interval and increased
      sympathetic activity has been demonstrated. This study aimed to evaluate Tp-e
      interval, Tp-e/QT ratio, and Tp-e/corrected QT interval (QTc) ratio in patients
      with MS before and after balloon valvuloplasty. METHODS: Thirty patients with
      severe MS and 30 sex-, body mass index-, and and age-matched healthy control
      subjects were enrolled. The severity of MS was defined following clinical,
      transthoracic, and transesophageal echocardiographic examinations. All patients
      underwent successful mitral balloon valvuloplasty. Tp-e interval, Tp-e/QT, and Tp
      e/QTc ratios were measured using 12-lead electrocardiogram. First, the
      abovementioned parameters were compared between patients with MS and healthy
      control subjects. Second, these parameters were compared before and after balloon
      valvuloplasty in patients with MS. RESULTS: The mean Tp-e interval was
      significantly prolonged in patients with MS compared with healthy control
      subjects (85.02+/-9.12 ms vs. 75.38+/-6.04 ms; p<0.001). In addition, Tp-e/QT
      ratio and Tp-e/QTc ratio were significantly higher in patients with MS than in
      healthy control subjects (0.217+/-0.025 vs. 0.196+/-0.02 and 0.203+/-0.02 vs.
      0.184+/-0.019; p<0.001).The mean valve area significantly increased after balloon
      valvuloplasty compared with that before balloon valvuloplasty (1.83+/-0.32 cm2
      vs. 1.18+/-0.15 cm2; p<0.001). Compared with those before balloon valvuloplasty,
      Tp-e interval (85.02+/-9.12 ms vs. 78.06+/-9.2 ms; p<0.001), Tp-e/QT ratio
      (0.217+/-0.02 vs. 0.201+/-0.02; p<0.001), and Tp-e/QTc ratio (0.203+/-0.02 vs.
      0.184+/-0.02; p<0.001) decreased after balloon valvuloplasty. CONCLUSION: We
      revealed that Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio increased in
      patients with severe MS. Furthermore, balloon valvuloplasty had a favorable
      effect on parameters associated with myocardial repolarization.

PMID- 29044095
TI  - Second-order spectral lineshapes from charged interfaces.
AB  - Second-order nonlinear spectroscopy has proven to be a powerful tool in
      elucidating key chemical and structural characteristics at a variety of
      interfaces. However, the presence of interfacial potentials may lead to
      complications regarding the interpretation of second harmonic and vibrational sum
      frequency generation responses from charged interfaces due to mixing of
      absorptive and dispersive contributions. Here, we examine by means of
      mathematical modeling how this interaction influences second-order spectral
      lineshapes. We discuss our findings in the context of reported nonlinear optical
      spectra obtained from charged water/air and solid/liquid interfaces and
      demonstrate the importance of accounting for the interfacial potential-dependent
      chi (3) term in interpreting lineshapes when seeking molecular information from
      charged interfaces using second-order spectroscopy.

PMID- 29044096
TI  - A homologue of the Parkinson's disease-associated protein LRRK2 undergoes a
      monomer-dimer transition during GTP turnover.
AB  - Mutations in LRRK2 are a common cause of genetic Parkinson's disease (PD). LRRK2
      is a multi-domain Roco protein, harbouring kinase and GTPase activity. In analogy
      with a bacterial homologue, LRRK2 was proposed to act as a GTPase activated by
      dimerization (GAD), while recent reports suggest LRRK2 to exist under a monomeric
      and dimeric form in vivo. It is however unknown how LRRK2 oligomerization is
      regulated. Here, we show that oligomerization of a homologous bacterial Roco
      protein depends on the nucleotide load. The protein is mainly dimeric in the
      nucleotide-free and GDP-bound states, while it forms monomers upon GTP binding,
      leading to a monomer-dimer cycle during GTP hydrolysis. An analogue of a PD
      associated mutation stabilizes the dimer and decreases the GTPase activity. This
      work thus provides insights into the conformational cycle of Roco proteins and
      suggests a link between oligomerization and disease-associated mutations in
      LRRK2.

PMID- 29044098
TI  - Ferrotoroidic ground state in a heterometallic {CrIIIDyIII6} complex displaying
      slow magnetic relaxation.
AB  - Toroidal quantum states are most promising for building quantum computing and
      information storage devices, as they are insensitive to homogeneous magnetic
      fields, but interact with charge and spin currents, allowing this moment to be
      manipulated purely by electrical means. Coupling molecular toroids into larger
      toroidal moments via ferrotoroidic interactions can be pivotal not only to
      enhance ground state toroidicity, but also to develop materials displaying
      ferrotoroidic ordered phases, which sustain linear magneto-electric coupling and
      multiferroic behavior. However, engineering ferrotoroidic coupling is known to be
      a challenging task. Here we have isolated a {CrIIIDyIII6} complex that exhibits
      the much sought-after ferrotoroidic ground state with an enhanced toroidal
      moment, solely arising from intramolecular dipolar interactions. Moreover, a
      theoretical analysis of the observed sub-Kelvin zero-field hysteretic spin
      dynamics of {CrIIIDyIII6} reveals the pivotal role played by ferrotoroidic states
      in slowing down the magnetic relaxation, in spite of large calculated single-ion
      quantum tunneling rates.

PMID- 29044099
TI  - Coherent coupling between a quantum dot and a donor in silicon.
AB  - Individual donors in silicon chips are used as quantum bits with extremely low
      error rates. However, physical realizations have been limited to one donor
      because their atomic size causes fabrication challenges. Quantum dot qubits, in
      contrast, are highly adjustable using electrical gate voltages. This
      adjustability could be leveraged to deterministically couple donors to quantum
      dots in arrays of qubits. In this work, we demonstrate the coherent interaction
      of a 31P donor electron with the electron of a metal-oxide-semiconductor quantum
      dot. We form a logical qubit encoded in the spin singlet and triplet states of
      the two-electron system. We show that the donor nuclear spin drives coherent
      rotations between the electronic qubit states through the contact hyperfine
      interaction. This provides every key element for compact two-electron spin qubits
      requiring only a single dot and no additional magnetic field gradients, as well
      as a means to interact with the nuclear spin qubit.

PMID- 29044097
TI  - DNA-binding of the Tet-transactivator curtails antigen-induced lymphocyte
      activation in mice.
AB  - The Tet-On/Off system for conditional transgene expression constitutes state-of
      the-art technology to study gene function by facilitating inducible expression in
      a timed and reversible manner. Several studies documented the suitability and
      versatility of this system to trace lymphocyte fate and to conditionally express
      oncogenes or silence tumour suppressor genes in vivo. Here, we show that
      expression of the tetracycline/doxycycline-controlled Tet-transactivator, while
      tolerated well during development and in immunologically unchallenged animals,
      impairs the expansion of antigen-stimulated T and B cells and thereby curtails
      adaptive immune responses in vivo. Transactivator-mediated cytotoxicity depends
      on DNA binding, but can be overcome by BCL2 overexpression, suggesting that
      apoptosis induction upon lymphocyte activation limits cellular and humoral immune
      responses. Our findings suggest a possible system-intrinsic biological bias of
      the Tet-On/Off system in vivo that will favour the outgrowth of apoptosis
      resistant clones, thus possibly confounding data published using such systems.

PMID- 29044100
TI  - Experimental realization of two-dimensional Dirac nodal line fermions in
      monolayer Cu2Si.
AB  - Topological nodal line semimetals, a novel quantum state of materials, possess
      topologically nontrivial valence and conduction bands that touch at a line near
      the Fermi level. The exotic band structure can lead to various novel properties,
      such as long-range Coulomb interaction and flat Landau levels. Recently,
      topological nodal lines have been observed in several bulk materials, such as
      PtSn4, ZrSiS, TlTaSe2 and PbTaSe2. However, in two-dimensional materials,
      experimental research on nodal line fermions is still lacking. Here, we report
      the discovery of two-dimensional Dirac nodal line fermions in monolayer Cu2Si
      based on combined theoretical calculations and angle-resolved photoemission
      spectroscopy measurements. The Dirac nodal lines in Cu2Si form two concentric
      loops centred around the Gamma point and are protected by mirror reflection
      symmetry. Our results establish Cu2Si as a platform to study the novel physical
      properties in two-dimensional Dirac materials and provide opportunities to
      realize high-speed low-dissipation devices.

PMID- 29044101
TI  - Controlling the bioactivity of a peptide hormone in vivo by reversible self
      assembly.
AB  - The use of peptides as therapeutic agents is undergoing a renaissance with the
      expectation of new drugs with enhanced levels of efficacy and safety. Their
      clinical potential will be only fully realised once their physicochemical and
      pharmacokinetic properties have been precisely controlled. Here we demonstrate a
      reversible peptide self-assembly strategy to control and prolong the bioactivity
      of a native peptide hormone in vivo. We show that oxyntomodulin, a peptide with
      potential to treat obesity and diabetes, self-assembles into a stable nanofibril
      formulation which subsequently dissociates to release active peptide and produces
      a pharmacological effect in vivo. The subcutaneous administration of the
      nanofibrils in rats results in greatly prolonged exposure, with a constant
      oxyntomodulin bioactivity detectable in serum for at least 5 days as compared to
      free oxyntomodulin which is undetectable after only 4 h. Such an approach is
      simple, cost-efficient and generic in addressing the limitations of peptide
      therapeutics.

PMID- 29044102
TI  - Ultrahigh thermoelectric power factor in flexible hybrid inorganic-organic
      superlattice.
AB  - Hybrid inorganic-organic superlattice with an electron-transmitting but phonon
      blocking structure has emerged as a promising flexible thin film thermoelectric
      material. However, the substantial challenge in optimizing carrier concentration
      without disrupting the superlattice structure prevents further improvement of the
      thermoelectric performance. Here we demonstrate a strategy for carrier
      optimization in a hybrid inorganic-organic superlattice of
      TiS2[tetrabutylammonium] x [hexylammonium] y , where the organic layers are
      composed of a random mixture of tetrabutylammonium and hexylammonium molecules.
      By vacuum heating the hybrid materials at an intermediate temperature, the
      hexylammonium molecules with a lower boiling point are selectively de
      intercalated, which reduces the electron density due to the requirement of
      electroneutrality. The tetrabutylammonium molecules with a higher boiling point
      remain to support and stabilize the superlattice structure. The carrier
      concentration can thus be effectively reduced, resulting in a remarkably high
      power factor of 904 uW m-1 K-2 at 300 K for flexible thermoelectrics, approaching
      the values achieved in conventional inorganic semiconductors.

PMID- 29044104
TI  - Mining drives extensive deforestation in the Brazilian Amazon.
AB  - Mining poses significant and potentially underestimated risks to tropical forests
      worldwide. In Brazil's Amazon, mining drives deforestation far beyond operational
      lease boundaries, yet the full extent of these impacts is unknown and thus
      neglected in environmental licensing. Here we quantify mining-induced
      deforestation and investigate the aspects of mining operations, which most likely
      contribute. We find mining significantly increased Amazon forest loss up to 70 km
      beyond mining lease boundaries, causing 11,670 km2 of deforestation between 2005
      and 2015. This extent represents 9% of all Amazon forest loss during this time
      and 12 times more deforestation than occurred within mining leases alone.
      Pathways leading to such impacts include mining infrastructure establishment,
      urban expansion to support a growing workforce, and development of mineral
      commodity supply chains. Mining-induced deforestation is not unique to Brazil; to
      mitigate adverse impacts of mining and conserve tropical forests globally,
      environmental assessments and licensing must considered both on- and off-lease
      sources of deforestation.

PMID- 29044103
TI  - OCT4 impedes cell fate redirection by the melanocyte lineage master regulator
      MITF in mouse ESCs.
AB  - Ectopic expression of lineage master regulators induces transdifferentiation.
      Whether cell fate transitions can be induced during various developmental stages
      has not been systemically examined. Here we discover that amongst different
      developmental stages, mouse embryonic stem cells (mESCs) are resistant to cell
      fate conversion induced by the melanocyte lineage master regulator MITF. By
      generating a transgenic system we exhibit that in mESCs, the pluripotency master
      regulator Oct4, counteracts pro-differentiation induced by Mitf by physical
      interference with MITF transcriptional activity. We further demonstrate that
      mESCs must be released from Oct4-maintained pluripotency prior to ectopically
      induced differentiation. Moreover, Oct4 induction in various differentiated cells
      represses their lineage identity in vivo. Alongside, chromatin architecture
      combined with ChIP-seq analysis suggest that Oct4 competes with various lineage
      master regulators for binding promoters and enhancers. Our analysis reveals
      pluripotency and transdifferentiation regulatory principles and could open new
      opportunities in the field of regenerative medicine.

PMID- 29044105
TI  - Late Holocene slowdown of the Indian Ocean Walker circulation.
AB  - Changes in tropical zonal atmospheric (Walker) circulation induce shifts in
      rainfall patterns along with devastating floods and severe droughts that
      dramatically impact the lives of millions of people. Historical records and
      observations of the Walker circulation over the 20th century disagree on the sign
      of change and therefore, longer climate records are necessary to better project
      tropical circulation changes in response to global warming. Here we examine
      proxies for thermocline depth and rainfall in the eastern tropical Indian Ocean
      during the globally colder Last Glacial Maximum (19-23 thousand years ago) and
      for the past 3000 years. We show that increased thermocline depth and rainfall
      indicate a stronger-than-today Walker circulation during the Last Glacial
      Maximum, which is supported by an ensemble of climate simulations. Our findings
      underscore the sensitivity of tropical circulation to temperature change and
      provide evidence for a further weakening of the Walker circulation in response to
      greenhouse warming.

PMID- 29044106
TI  - A mechanosensitive Ca2+ channel activity is dependent on the developmental
      regulator DEK1.
AB  - Responses of cells to mechanical stress are thought to be critical in
      coordinating growth and development. Consistent with this idea, mechanically
      activated channels play important roles in animal development. For example, the
      PIEZO1 channel controls cell division and epithelial-layer integrity and is
      necessary for vascular development in mammals. In plants, the actual contribution
      of mechanoperception to development remains questionable because very few
      putative mechanosensors have been identified and the phenotypes of the
      corresponding mutants are rather mild. Here, we show that the Arabidopsis
      Defective Kernel 1 (DEK1) protein, which is essential for development beyond
      early embryogenesis, is associated with a mechanically activated Ca2+ current in
      planta, suggesting that perception of mechanical stress plays a critical role in
      plant development.

PMID- 29044107
TI  - Triparental plants provide direct evidence for polyspermy induced polyploidy.
AB  - It is considered an inviolable principle that sexually reproducing organisms have
      no more than two parents and fertilization of an egg by multiple sperm
      (polyspermy) is lethal in many eukaryotes. In flowering plants polyspermy has
      remained a hypothetical concept, due to the lack of tools to unambiguously
      identify and trace this event. We established a high-throughput polyspermy
      detection assay, which uncovered that supernumerary sperm fusion does occur in
      planta and can generate viable polyploid offspring. Moreover, polyspermy can give
      rise to seedlings with one mother and two fathers, challenging the bi-organismal
      concept of parentage. The polyspermy derived triploids are taller and produce
      bigger organs than plants resulting from a regular monospermic fertilization. In
      addition, we demonstrate the hybridization potential of polyspermy by instantly
      combining three different Arabidopsis accessions in one zygote. Our results
      provide direct evidence for polyspermy as a route towards polyploidy, which is
      considered a major plant speciation mechanism.

PMID- 29044110
TI  - Hyperconnected molecular glass network architectures with exceptional elastic
      properties.
AB  - Hyperconnected network architectures can endow nanomaterials with remarkable
      mechanical properties that are fundamentally controlled by designing connectivity
      into the intrinsic molecular structure. For hybrid organic-inorganic
      nanomaterials, here we show that by using 1,3,5 silyl benzene precursors, the
      connectivity of a silicon atom within the network extends beyond its chemical
      coordination number, resulting in a hyperconnected network with exceptional
      elastic stiffness, higher than that of fully dense silica. The exceptional
      intrinsic stiffness of these hyperconnected glass networks is demonstrated with
      molecular dynamics models and these model predictions are calibrated through the
      synthesis and characterization of an intrinsically porous hybrid glass processed
      from 1,3,5(triethoxysilyl)benzene. The proposed molecular design strategy applies
      to any materials system wherein the mechanical properties are controlled by the
      underlying network connectivity.

PMID- 29044108
TI  - Echinochloa crus-galli genome analysis provides insight into its adaptation and
      invasiveness as a weed.
AB  - Barnyardgrass (Echinochloa crus-galli) is a pernicious weed in agricultural
      fields worldwide. The molecular mechanisms underlying its success in the absence
      of human intervention are presently unknown. Here we report a draft genome
      sequence of the hexaploid species E. crus-galli, i.e., a 1.27 Gb assembly
      representing 90.7% of the predicted genome size. An extremely large repertoire of
      genes encoding cytochrome P450 monooxygenases and glutathione S-transferases
      associated with detoxification are found. Two gene clusters involved in the
      biosynthesis of an allelochemical 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one
      (DIMBOA) and a phytoalexin momilactone A are found in the E. crus-galli genome,
      respectively. The allelochemical DIMBOA gene cluster is activated in response to
      co-cultivation with rice, while the phytoalexin momilactone A gene cluster
      specifically to infection by pathogenic Pyricularia oryzae. Our results provide a
      new understanding of the molecular mechanisms underlying the extreme adaptation
      of the weed.

PMID- 29044111
TI  - Elevated olivine weathering rates and sulfate formation at cryogenic temperatures
      on Mars.
AB  - Large Hesperian-aged (~3.7 Ga) layered deposits of sulfate-rich sediments in the
      equatorial regions of Mars have been suggested to be evidence for ephemeral playa
      environments. But early Mars may not have been warm enough to support conditions
      similar to what occurs in arid environments on Earth. Instead cold, icy
      environments may have been widespread. Under cryogenic conditions sulfate
      formation might be blocked, since kinetics of silicate weathering are typically
      strongly retarded at temperatures well below 0  degrees C. But cryo-concentration
      of acidic solutions may counteract the slow kinetics. Here we show that cryo
      concentrated acidic brines rapidly chemically weather olivine minerals and form
      sulfate minerals at temperatures as low as -60  degrees C. These experimental
      results demonstrate the viability of sulfate formation under current Martian
      conditions, even in the polar regions. An ice-hosted sedimentation and weathering
      model may provide a compelling description of the origin of large Hesperian-aged
      layered sulfate deposits on Mars.

PMID- 29044109
TI  - APOBEC3H structure reveals an unusual mechanism of interaction with duplex RNA.
AB  - The APOBEC3 family of cytidine deaminases cause lethal hypermutation of
      retroviruses via deamination of newly reverse-transcribed viral DNA. Their
      ability to bind RNA is essential for virion infiltration and antiviral activity,
      yet the mechanisms of viral RNA recognition are unknown. By screening naturally
      occurring, polymorphic, non-human primate APOBEC3H variants for biological and
      crystallization properties, we obtained a 2.24-A crystal structure of pig-tailed
      macaque APOBEC3H with bound RNA. Here, we report that APOBEC3H forms a dimer
      around a short RNA duplex and, despite the bound RNA, has potent cytidine
      deaminase activity. The structure reveals an unusual RNA-binding mode in which
      two APOBEC3H molecules at opposite ends of a seven-base-pair duplex interact
      extensively with both RNA strands, but form no protein-protein contacts. CLIP-seq
      analysis revealed that APOBEC3H preferentially binds to sequences in the viral
      genome predicted to contain duplexes, a property that may facilitate both virion
      incorporation and catalytic activity.

PMID- 29044113
TI  - Large second harmonic generation enhancement in Si3N4 waveguides by all-optically
      induced quasi-phase-matching.
AB  - Efficient second harmonic generation in integrated platforms is usually achieved
      by resonant structures, intermodal phase-matching or quasi-phase matching by
      periodically poling ferroelectric waveguides. However, in all these structures,
      it is impossible to reconfigure the phase-matching condition in an all-optical
      way. Here, we demonstrate that a Watt-level laser causes a periodic modification
      of the second-order susceptibility in a silicon nitride waveguide, allowing for
      quasi-phase-matching between the pump and second harmonic modes for arbitrary
      wavelengths inside the erbium band. The grating is long-term inscribed, and leads
      to a second harmonic generation enhancement of more than 30 dB. We estimate a chi
      (2) on the order of 0.3 pm/V, with a maximum conversion efficiency of 0.05% W-1.
      We explain the observed phenomenon with the coherent photogalvanic effect model,
      which correctly agrees with the retrieved experimental parameters.

PMID- 29044112
TI  - Cognitive task information is transferred between brain regions via resting-state
      network topology.
AB  - Resting-state network connectivity has been associated with a variety of
      cognitive abilities, yet it remains unclear how these connectivity properties
      might contribute to the neurocognitive computations underlying these abilities.
      We developed a new approach-information transfer mapping-to test the hypothesis
      that resting-state functional network topology describes the computational
      mappings between brain regions that carry cognitive task information. Here, we
      report that the transfer of diverse, task-rule information in distributed brain
      regions can be predicted based on estimated activity flow through resting-state
      network connections. Further, we find that these task-rule information transfers
      are coordinated by global hub regions within cognitive control networks. Activity
      flow over resting-state connections thus provides a large-scale network mechanism
      for cognitive task information transfer and global information coordination in
      the human brain, demonstrating the cognitive relevance of resting-state network
      topology.

PMID- 29044115
TI  - Carbon fixation from mineral carbonates.
AB  - Photoautotrophs assimilate oxidized carbon obtained from one of two sources:
      dissolved or atmospheric. Despite its size, the pool of lithospheric carbonate is
      not known to be a direct source for autotrophy. Yet, the mechanism that
      euendolithic cyanobacteria use to excavate solid carbonates suggests that
      minerals could directly supply CO2 for autotrophy. Here, we use stable isotopes
      and NanoSIMS to show that the cyanobacterium Mastigocoleus testarum derives most
      of its carbon from the mineral it excavates, growing preferentially as an
      endolith when lacking dissolved CO2. Furthermore, natural endolithic communities
      from intertidal marine carbonate outcrops present carbon isotopic signatures
      consistent with mineral-sourced autotrophy. These data demonstrate a direct
      geomicrobial link between mineral carbonate pools and reduced organic carbon,
      which, given the geographical extent of carbonate outcrops, is likely of global
      relevance. The ancient fossil record of euendolithic cyanobacteria suggests that
      biological fixation of solid carbonate could have been relevant since the mid
      Proterozoic.

PMID- 29044114
TI  - Evolution of drift robustness in small populations.
AB  - Most mutations are deleterious and cause a reduction in population fitness known
      as the mutational load. In small populations, weakened selection against slightly
      deleterious mutations results in an additional fitness reduction. Many studies
      have established that populations can evolve a reduced mutational load by
      evolving mutational robustness, but it is uncertain whether small populations can
      evolve a reduced susceptibility to drift-related fitness declines. Here, using
      mathematical modeling and digital experimental evolution, we show that small
      populations do evolve a reduced vulnerability to drift, or 'drift robustness'. We
      find that, compared to genotypes from large populations, genotypes from small
      populations have a decreased likelihood of small-effect deleterious mutations,
      thus causing small-population genotypes to be drift-robust. We further show that
      drift robustness is not adaptive, but instead arises because small populations
      can only maintain fitness on drift-robust fitness peaks. These results have
      implications for genome evolution in organisms with small effective population
      sizes.

PMID- 29044116
TI  - Author Correction: Ctenophore relationships and their placement as the sister
      group to all other animals.
AB  - In the version of this Article originally published the location of Punta Arenas
      was incorrect and should have read 'Chile' in Figures 3-5 and in the
      Supplementary Information. This has been corrected in all versions of the
      Article.

PMID- 29044118
TI  - Younger Dryas ice margin retreat triggered by ocean surface warming in central
      eastern Baffin Bay.
AB  - The transition from the last ice age to the present-day interglacial was
      interrupted by the Younger Dryas (YD) cold period. While many studies exist on
      this climate event, only few include high-resolution marine records that span the
      YD. In order to better understand the interactions between ocean, atmosphere and
      ice sheet stability during the YD, more high-resolution proxy records from the
      Arctic, located proximal to ice sheet outlet glaciers, are required. Here we
      present the first diatom-based high-resolution quantitative reconstruction of sea
      surface conditions from central-eastern Baffin Bay, covering the period 14.0-10.2
      kyr BP. Our record reveals warmer sea surface conditions and strong interactions
      between the ocean and the West Greenland ice margin during the YD. These warmer
      conditions were caused by increased Atlantic-sourced water inflow combined with
      amplified seasonality. Our results emphasize the importance of the ocean for ice
      sheet stability under the current changing climate.

PMID- 29044117
TI  - ROCK regulates the intermittent mode of interstitial T cell migration in inflamed
      lungs.
AB  - Effector T cell migration through tissues can enable control of infection or
      mediate inflammatory damage. Nevertheless, the molecular mechanisms that regulate
      migration of effector T cells within the interstitial space of inflamed lungs are
      incompletely understood. Here, we show T cell migration in a mouse model of acute
      lung injury with two-photon imaging of intact lung tissue. Computational analysis
      indicates that T cells migrate with an intermittent mode, switching between
      confined and almost straight migration, guided by lung-associated vasculature.
      Rho-associated protein kinase (ROCK) is required for both high-speed migration
      and straight motion. By contrast, inhibition of Galphai signaling with pertussis
      toxin affects speed but not the intermittent migration of lung-infiltrating T
      cells. Computational modeling shows that an intermittent migration pattern
      balances both search area and the duration of contacts between T cells and target
      cells. These data identify that ROCK-dependent intermittent T cell migration
      regulates tissue-sampling during acute lung injury.

PMID- 29044120
TI  - Few-femtosecond passage of conical intersections in the benzene cation.
AB  - Observing the crucial first few femtoseconds of photochemical reactions requires
      tools typically not available in the femtochemistry toolkit. Such dynamics are
      now within reach with the instruments provided by attosecond science. Here, we
      apply experimental and theoretical methods to assess the ultrafast nonadiabatic
      vibronic processes in a prototypical complex system-the excited benzene cation.
      We use few-femtosecond duration extreme ultraviolet and visible/near-infrared
      laser pulses to prepare and probe excited cationic states and observe two
      relaxation timescales of 11 +/- 3 fs and 110 +/- 20 fs. These are interpreted in
      terms of population transfer via two sequential conical intersections. The
      experimental results are quantitatively compared with state-of-the-art multi
      configuration time-dependent Hartree calculations showing convincing agreement in
      the timescales. By characterising one of the fastest internal conversion
      processes studied to date, we enter an extreme regime of ultrafast molecular
      dynamics, paving the way to tracking and controlling purely electronic dynamics
      in complex molecules.

PMID- 29044119
TI  - The WNT target SP5 negatively regulates WNT transcriptional programs in human
      pluripotent stem cells.
AB  - The WNT/beta-catenin signaling pathway is a prominent player in many
      developmental processes, including gastrulation, anterior-posterior axis
      specification, organ and tissue development, and homeostasis. Here, we use human
      pluripotent stem cells (hPSCs) to study the dynamics of the transcriptional
      response to exogenous activation of the WNT pathway. We describe a mechanism
      involving the WNT target gene SP5 that leads to termination of the
      transcriptional program initiated by WNT signaling. Integration of gene
      expression profiles of wild-type and SP5 mutant cells with genome-wide SP5
      binding events reveals that SP5 acts to diminish expression of genes previously
      activated by the WNT pathway. Furthermore, we show that activation of SP5 by WNT
      signaling is most robust in cells with developmental potential, such as stem
      cells. These findings indicate a mechanism by which the developmental WNT
      signaling pathway reins in expression of transcriptional programs.

PMID- 29044121
TI  - Robust Bain distortion in the premartensite phase of a platinum-substituted
      Ni2MnGa magnetic shape memory alloy.
AB  - The premartensite phase of shape memory and magnetic shape memory alloys (MSMAs)
      is believed to be a precursor state of the martensite phase with preserved
      austenite phase symmetry. The thermodynamic stability of the premartensite phase
      and its relation to the martensitic phase is still an unresolved issue, even
      though it is critical to the understanding of the functional properties of MSMAs.
      We present here unambiguous evidence for macroscopic symmetry breaking leading to
      robust Bain distortion in the premartensite phase of 10% Pt-substituted Ni2MnGa.
      We show that the robust Bain-distorted premartensite (T2) phase results from
      another premartensite (T1) phase with preserved cubic-like symmetry through an
      isostructural phase transition. The T2 phase finally transforms to the martensite
      phase with additional Bain distortion on further cooling. Our results demonstrate
      that the premartensite phase should not be considered as a precursor state with
      the preserved symmetry of the cubic austenite phase.

PMID- 29044122
TI  - Wind loads and competition for light sculpt trees into self-similar structures.
AB  - Trees are self-similar structures: their branch lengths and diameters vary
      allometrically within the tree architecture, with longer and thicker branches
      near the ground. These tree allometries are often attributed to optimisation of
      hydraulic sap transport and safety against elastic buckling. Here, we show that
      these allometries also emerge from a model that includes competition for light,
      wind biomechanics and no hydraulics. We have developed MECHATREE, a numerical
      model of trees growing and evolving on a virtual island. With this model, we
      identify the fittest growth strategy when trees compete for light and allocate
      their photosynthates to grow seeds, create new branches or reinforce existing
      ones in response to wind-induced loads. Strikingly, we find that selected trees
      species are self-similar and follow allometric scalings similar to those observed
      on dicots and conifers. This result suggests that resistance to wind and
      competition for light play an essential role in determining tree allometries.

PMID- 29044123
TI  - IRE1alpha/XBP1s branch of UPR links HIF1alpha activation to mediate ANGII
      dependent endothelial dysfunction under particulate matter (PM) 2.5 exposure.
AB  - Short- and long-term exposure to particulate matter (PM) 2.5 instigates adverse
      health effect upon the cardiovascular (CV) system. Disclosing the molecular
      events by which PM2.5 evokes CV injuries is essential in developing effective
      risk-reduction strategy. Here we found that rats after intratracheally
      instillation with PM2.5 displayed increased circulating level of ANGII, the major
      bioactive peptide in renin-angiotensin-system (RAS), which resulted from the
      elevation of ANGII production in the vascular endothelium. Further investigations
      demonstrated that activation of IRE1alpha/XBP1s branch of unfolded protein
      response (UPR) was essential for augmented vascular ANGII signaling in response
      to PM2.5 exposure, whose effects strictly depends on the assembly of
      XBP1s/HIF1alpha transcriptional complex. Moreover, ablation of IRE1/XBP1/HIFalpha
      dependent ACE/ANGII/AT1R axis activation inhibited oxidative stress and
      proinflammatory response in the vascular endothelial cells induced by PM2.5.
      Therefore, we conclude that PM2.5 exposure instigates endoplasmic reticulum
      instability, leading to the induction of IRE1alpha/XBP1s branch of UPR and links
      HIF1alpha transactivation to mediate ANGII-dependent endothelial dysfunction.
      Identifying novel therapeutic targets to alleviate ER stress and restore local
      RAS homeostasis in the endothelium may be helpful for the management of PM2.5
      induced CV burden.

PMID- 29044124
TI  - Unconventional two-dimensional vibrations of a decorated carbon nanotube under
      electric field: linking actuation to advanced sensing ability.
AB  - We show that a carbon nanotube decorated with different types of charged metallic
      nanoparticles exhibits unusual two-dimensional vibrations when actuated by
      applied electric field. Such vibrations and diverse possible trajectories are not
      only fundamentally important but also have minimum two characteristic frequencies
      that can be directly linked back to the properties of the constituents in the
      considered nanoresonator. Namely, those frequencies and the maximal deflection
      during vibrations are very distinctively dependent on the geometry of the
      nanotube, the shape, element, mass and charge of the nanoparticle, and are vastly
      tunable by the applied electric field, revealing the unique sensing ability of
      devices made of molecular filaments and metallic nanoparticles.

PMID- 29044125
TI  - Transcription Factor CTIP1/ BCL11A Regulates Epidermal Differentiation and Lipid
      Metabolism During Skin Development.
AB  - The epidermal permeability barrier (EPB) prevents organisms from dehydration and
      infection. The transcriptional regulation of EPB development is poorly
      understood. We demonstrate here that transcription factor COUP-TF-interacting
      protein 1 (CTIP1/BCL11A; hereafter CTIP1) is highly expressed in the developing
      murine epidermis. Germline deletion of Ctip1 (Ctip1 -/-) results in EPB defects
      accompanied by compromised epidermal differentiation, drastic reduction in
      profilaggrin processing, reduced lamellar bodies in granular layers and
      significantly altered lipid composition. Transcriptional profiling of Ctip1 -/-
      embryonic skin identified altered expression of genes encoding lipid-metabolism
      enzymes, skin barrier-associated transcription factors and junctional proteins.
      CTIP1 was observed to interact with genomic elements within the regulatory region
      of the gene encoding the differentiation-associated gene, Fos-related antigen2
      (Fosl2) and lipid-metabolism-related gene, Fatty acid elongase 4 (Elvol4), and
      the expression of both was altered in Ctip1 -/- mice. CTIP1 appears to play a
      role in EPB establishment of via direct or indirect regulation of a subset of
      genes encoding proteins involved in epidermal differentiation and lipid
      metabolism. These results identify potential, CTIP1-regulated avenues for
      treatment of skin disorders involving EBP defects.

PMID- 29044126
TI  - Understanding pup affective state through ethologically significant ultrasonic
      vocalization frequency.
AB  - Throughout life, rats emit ultrasonic vocalizations (USV) when confronted with an
      aversive situation. However, the conditions classically used to elicit USV vary
      greatly with the animal's age (isolation from the dam in infancy, versus
      nociceptive stimulation in adults). The present study is the first to
      characterize USV responses to the same aversive event throughout development.
      Specifically, infant, juvenile and adult rats were presented with mild foot
      shocks and their USV frequency, duration, and relationship with respiration and
      behavior were compared. In juvenile and adult rats, a single class of USV is
      observed with an age-dependent main frequency and duration (30 kHz/400 ms in
      juveniles, 22 kHz/900 ms in adults). In contrast, infant rat USV were split into
      two classes with specific relationships with respiration and behavior: 40 kHz/300
      ms and 66 kHz/21 ms. Next, we questioned if these infant USV were also emitted in
      a more naturalistic context by exposing pups to interactions with the mother
      treating them roughly. This treatment enhanced 40-kHz USV while leaving 66-kHz
      USV unchanged suggesting that the use of USV goes far beyond a signal studied in
      terms of amount of emission, and can inform us about some aspects of the infant's
      affective state.

PMID- 29044127
TI  - Engineered in-vitro cell line mixtures and robust evaluation of computational
      methods for clonal decomposition and longitudinal dynamics in cancer.
AB  - Characterization and quantification of tumour clonal populations over time via
      longitudinal sampling are essential components in understanding and predicting
      the response to therapeutic interventions. Computational methods for inferring
      tumour clonal composition from deep-targeted sequencing data are ubiquitous,
      however due to the lack of a ground truth biological data, evaluating their
      performance is difficult. In this work, we generate a benchmark data set that
      simulates tumour longitudinal growth and heterogeneity by in vitro mixing of
      cancer cell lines with known proportions. We apply four different algorithms to
      our ground truth data set and assess their performance in inferring clonal
      composition using different metrics. We also analyse the performance of these
      algorithms on breast tumour xenograft samples. We conclude that methods that can
      simultaneously analyse multiple samples while accounting for copy number
      alterations as a factor in allelic measurements exhibit the most accurate
      predictions. These results will inform future functional genomics oriented
      studies of model systems where time series measurements in the context of
      therapeutic interventions are becoming increasingly common. These studies will
      need computational models which accurately reflect the multi-factorial nature of
      allele measurement in cancer including, as we show here, segmental aneuploidies.

PMID- 29044128
TI  - Effects of vessel traffic and underwater noise on the movement, behaviour and
      vocalisations of bottlenose dolphins in an urbanised estuary.
AB  - ABSTARCT: The potential disturbance of dolphins from tourism boats has been
      widely discussed in the literature, in terms of both physical vessel presence and
      associated underwater noise. However, less attention has been paid to the
      potential impact of non-tourism vessels, despite these being much more widespread
      and occurring in greater numbers throughout coastal dolphin habitats. The Indo
      Pacific bottlenose dolphin (T. aduncus) community using the Fremantle Inner
      Harbour, Western Australia, is exposed to high levels of vessel traffic. To
      investigate whether behavioural responses could be occurring, a non-invasive
      combination of visual and acoustic monitoring was conducted using a theodolite
      and an autonomous acoustic logger. Dolphins significantly increased their average
      movement speeds in high vessel densities, but only for some activity states.
      Behavioural budgets also changed in the presence of vessels, with animals
      spending greater time travelling and less time resting or socialising. Finally,
      multiple whistle characteristics varied with rising levels of broadband noise,
      and other contextual variables. Despite being acoustically specialised for higher
      frequencies, dolphins had the strongest acoustic variation during low-frequency
      noise. This study highlights the complexity of disturbance responses in this
      species, confirming the need for consideration of both surface and acoustic
      behaviour alongside appropriate contextual data.

PMID- 29044129
TI  - Priming with FGF2 stimulates human dental pulp cells to promote axonal
      regeneration and locomotor function recovery after spinal cord injury.
AB  - Human dental pulp cells (DPCs), adherent cells derived from dental pulp tissues,
      are potential tools for cell transplantation therapy. However, little work has
      been done to optimize such transplantation. In this study, DPCs were treated with
      fibroblast growth factor-2 (FGF2) for 5-6 consecutive serial passages and were
      transplanted into the injury site immediately after complete transection of the
      rat spinal cord. FGF2 priming facilitated the DPCs to promote axonal regeneration
      and to improve locomotor function in the rat with spinal cord injury (SCI).
      Additional analyses revealed that FGF2 priming protected cultured DPCs from
      hydrogen-peroxide-induced cell death and increased the number of DPCs in the SCI
      rat spinal cord even 7 weeks after transplantation. The production of major
      neurotrophic factors was equivalent in FGF2-treated and untreated DPCs. These
      observations suggest that FGF2 priming might protect DPCs from the post-trauma
      microenvironment in which DPCs infiltrate and resident immune cells generate
      cytotoxic reactive oxygen species. Surviving DPCs could increase the availability
      of neurotrophic factors in the lesion site, thereby promoting axonal regeneration
      and locomotor function recovery.

PMID- 29044131
TI  - Growth-Induced In-Plane Uniaxial Anisotropy in V2O3/Ni Films.
AB  - We report on a strain-induced and temperature dependent uniaxial anisotropy in
      V2O3/Ni hybrid thin films, manifested through the interfacial strain and sample
      microstructure, and its consequences on the angular dependent magnetization
      reversal. X-ray diffraction and reciprocal space maps identify the in-plane
      crystalline axes of the V2O3; atomic force and scanning electron microscopy
      reveal oriented rips in the film microstructure. Quasi-static magnetometry and
      dynamic ferromagnetic resonance measurements identify a uniaxial magnetic easy
      axis along the rips. Comparison with films grown on sapphire without rips shows a
      combined contribution from strain and microstructure in the V2O3/Ni films.
      Magnetization reversal characteristics captured by angular-dependent first order
      reversal curve measurements indicate a strong domain wall pinning along the
      direction orthogonal to the rips, inducing an angular-dependent change in the
      reversal mechanism. The resultant anisotropy is tunable with temperature and is
      most pronounced at room temperature, which is beneficial for potential device
      applications.

PMID- 29044130
TI  - Long-term passive acoustic recordings track the changing distribution of North
      Atlantic right whales (Eubalaena glacialis) from 2004 to 2014.
AB  - Given new distribution patterns of the endangered North Atlantic right whale
      (NARW; Eubalaena glacialis) population in recent years, an improved understanding
      of spatio-temporal movements are imperative for the conservation of this species.
      While so far visual data have provided most information on NARW movements,
      passive acoustic monitoring (PAM) was used in this study in order to better
      capture year-round NARW presence. This project used PAM data from 2004 to 2014
      collected by 19 organizations throughout the western North Atlantic Ocean.
      Overall, data from 324 recorders (35,600 days) were processed and analyzed using
      a classification and detection system. Results highlight almost year-round
      habitat use of the western North Atlantic Ocean, with a decrease in detections in
      waters off Cape Hatteras, North Carolina in summer and fall. Data collected post
      2010 showed an increased NARW presence in the mid-Atlantic region and a
      simultaneous decrease in the northern Gulf of Maine. In addition, NARWs were
      widely distributed across most regions throughout winter months. This study
      demonstrates that a large-scale analysis of PAM data provides significant value
      to understanding and tracking shifts in large whale movements over long time
      scales.

PMID- 29044132
TI  - Enhancement mechanisms of short-time aerobic digestion for waste activated sludge
      in the presence of cocoamidopropyl betaine.
AB  - Cocoamidopropyl betaine (CAPB), which is a biodegradable ampholytic surfactant,
      has recently been found to dramatically enhance the aerobic digestion of waste
      activated sludge (WAS) in short-time aerobic digestion (STAD) systems. Therefore,
      it is important to understand the mechanisms in which CAPB enhances WAS aerobic
      digestion performance. Results showed that CAPB could dramatically enhance the
      solubilization of soluble proteins (PN), polysaccharides (PS), nucleic acids (NA)
      and humic-like substances (HS) in the STAD system within the initial 2 h. Then
      PN, PS and NA gradually decreased, while HS showed only minor decease. In
      addition, CAPB increased the proportion of low MW fractions (<20 kDa) from 4.22%
      to 39.4%, which are more biodegradable. Specific oxygen uptake rates and
      dehydrogenase enzyme activity results indicated that CAPB markedly improved the
      aerobic microorganism activities. Microbial community analyses and principle
      coordinate analyses (PCoA) revealed that CAPB increased the proportion of some
      functional microorganisms, including Proteobacteria, Planctomycetales,
      Acinetobacter, Pseudomonas and Aeromonas. The changes driven by CAPB could
      explain the enhanced performance of the STAD system for WAS aerobic treatment.

PMID- 29044133
TI  - Effects of water availability on a forestry pathosystem: fungal strain-specific
      variation in disease severity.
AB  - Norway spruce is one of the most important commercial forestry species in Europe,
      and is commonly infected by the bark beetle-vectored necrotrophic fungus,
      Endoconidiophora polonica. Spruce trees display a restricted capacity to respond
      to environmental perturbations, and we hypothesized that water limitation will
      increase disease severity in this pathosystem. To test this prediction, 737
      seedlings were randomized to high (W+) or low (W-) water availability treatment
      groups, and experimentally inoculated with one of three E. polonica strains or
      mock-inoculated. Seedling mortality was monitored throughout an annual growing
      season, and total seedling growth and lesion length indices were measured at the
      experiment conclusion. Seedling growth was greater in the W+ than W- treatment
      group, demonstrating limitation due to water availability. For seedlings infected
      with two of the fungal strains, no differences in disease severity occurred in
      response to water availability. For the third fungal strain, however, greater
      disease severity (mortality and lesion lengths) occurred in W- than W+ seedlings.
      While the co-circulation in nature of multiple E. polonica strains of varying
      virulence is known, this is the first experimental evidence that water
      availability can alter strain-specific disease severity.

PMID- 29044134
TI  - Impact of ocean warming on sustainable fisheries management informs the Ecosystem
      Approach to Fisheries.
AB  - An integrated ecosystem model including fishing and the impact of rising
      temperatures, relative to species' thermal ranges, was used to assess the
      cumulative effect of future climate change and sustainable levels of fishing
      pressure on selected target species. Historically, important stocks of cod and
      whiting showed declining trends caused by high fisheries exploitation and strong
      top-down control by their main predators (grey seals and saithe). In a no-change
      climate scenario these stocks recovered under sustainable management scenarios
      due to the cumulative effect of reduced fishing and predation mortalities
      cascading through the food-web. However, rising temperature jeopardised boreal
      stenothermal species: causing severe declines in grey seals, cod, herring and
      haddock, while eurythermal species were not affected. The positive effect of a
      higher optimum temperature for whiting, in parallel with declines of its
      predators such as seals and cod, resulted in a strong increase for this stock
      under rising temperature scenarios, indicating a possible change in the
      contribution of stocks to the overall catch by the end of the century. These
      results highlight the importance of including environmental change in the
      ecosystem approach to achieve sustainable fisheries management.

PMID- 29044135
TI  - Long-term toxicity of ZnO nanoparticles to Scenedesmus rubescens cultivated in
      different media.
AB  - The aim of this work was to investigate the long-term toxic effect of zinc oxide
      (ZnO) nanoparticles (NPs) on freshwater microalgae, combined with the nutrient
      consumption in the culture. For this purpose, two common microalgae media (Blue
      Green 11, BG-11, and Bold's Basal Medium, BBM) were used. Scenedesmus rubescens
      was used as freshwater microalgae model species and was exposed to ZnO NPs at
      different concentrations (0.081 to 810 mg/L) for a period up to 28 d. The
      experimental results revealed that microalgae growth was affected by the time of
      exposure and the NPs concentrations, but mainly the culture medium used.
      Differences in microalgae growth rates were observed and attributed to the
      selected culture medium. The toxic effect of ZnO NPs was higher on microalgae
      cultured in modified BG-11 compared to BBM, despite the fact that S. rubescens
      exhibited higher growth rate in modified BG-11 without the exposure of ZnO NPs.

PMID- 29044136
TI  - New insights into the impacts of suspended particulate matter on phytoplankton
      density in a tributary of the Three Gorges Reservoir, China.
AB  - Phytoplankton density can be influenced by a wide range of factors whereas the
      role of suspended particulate matter (SPM) are not clear in river that annually
      subjected to hydrodynamics shift. Here, spatial-temporal variation of
      environmental parameters and phytoplankton density were studied from January 2013
      to December 2014 in Yulin River, a tributary of the Three Gorges Reservoir,
      China. Laboratory experiments were conducted to elucidate the key parameter and
      interpret how it impacted phytoplankton density. SPM is negatively correlated
      with phytoplankton density. Despite SPM in Yulin River revealed weaker NH3-N, NO3
      N and PO4-P adsorption capabilities in comparison to that in other aquatic
      ecosystems, increase of water velocity from 0.1 to 0.8 m/s led to approximately
      6.8-times increase of light attenuation rate. In experiments evaluating the
      aggregation of Chlorella pyrenoidosa upon SPM, floc size showed 7.4 to 22% fold
      increase compared to the SPM or algae itself, which was due to the interaction
      between SPM and phytoplankton extracellular polymeric substances. Our results
      suggest that SPM could contribute to the variation of phytoplankton density
      through the integrated process including light attenuation, nutrient adsorption
      and algae aggregation. This is the first evaluation of the multiple processes
      underlying the impact of SPM on phytoplankton.

PMID- 29044137
TI  - The soothing function of touch: affective touch reduces feelings of social
      exclusion.
AB  - The mammalian need for social proximity, attachment and belonging may have an
      adaptive and evolutionary value in terms of survival and reproductive success.
      Consequently, ostracism may induce strong negative feelings of social exclusion.
      Recent studies suggest that slow, affective touch, which is mediated by a
      separate, specific C tactile neurophysiological system than faster, neutral
      touch, modulates the perception of physical pain. However, it remains unknown
      whether slow, affective touch, can also reduce feelings of social exclusion, a
      form of social pain. Here, we employed a social exclusion paradigm, namely the
      Cyberball task (N = 84), to examine whether the administration of slow, affective
      touch may reduce the negative feelings of ostracism induced by the social
      exclusion manipulations of the Cyberball task. As predicted, the provision of
      slow-affective, as compared to fast-neutral, touch led to a specific decrease in
      feelings of social exclusion, beyond general mood effects. These findings point
      to the soothing function of slow, affective touch, particularly in the context of
      social separation or rejection, and suggest a specific relation between affective
      touch and social bonding.

PMID- 29044138
TI  - The neonicotinoid insecticide Clothianidin adversely affects immune signaling in
      a human cell line.
AB  - Clothianidin is a widely used neonicotinoid insecticide, which is a potent
      agonist of the nicotinic acetylcholine receptor in insects. This neurotoxic
      compound has a negative impact on insect immunity, as it down-regulates the
      activation of the transcription factor NF-kappaB. Given the evolutionary
      conserved role of NF-kappaB in the modulation of the immune response in the
      animal kingdom, here we want to assess any effect of Clothianidin on vertebrate
      defense barriers. In presence of this neonicotinoid insecticide, a pro
      inflammatory challenge with LPS on the human monocytic cell line THP-1 results
      both in a reduced production of the cytokine TNF-alpha and in a down-regulation
      of a reporter gene under control of NF-kappaB promoter. This finding is
      corroborated by a significant impact of Clothianidin on the transcription levels
      of different immune genes, characterized by a core disruption of TRAF4 and TRAF6
      that negatively influences NF-kappaB signaling. Moreover, exposure to
      Clothianidin concurrently induces a remarkable up-regulation of NGFR, which
      supports the occurrence of functional ties between the immune and nervous
      systems. These results suggest a potential risk of immunotoxicity that
      neonicotinoids may have on vertebrates, which needs to be carefully assessed at
      the organism level.

PMID- 29044139
TI  - Diabetes in Iran: Prospective Analysis from First Nationwide Diabetes Report of
      National Program for Prevention and Control of Diabetes (NPPCD-2016).
AB  - We estimated proportions of different types of diabetes, comorbidities, treatment
      (the use of oral glucose-lowering agents and insulin), control (hyperglycemia,
      dyslipidemia and hypertension) and chronic microvascular and macrovascular
      complications among people with diabetes presenting to the tertiary-care academic
      diabetes outpatient clinics in Iran. This study is the prospective analysis of
      data (n = 30,202) from the registry of university-affiliated adult outpatient
      diabetes clinics in the country during 2015-2016. The proportions of type 1
      diabetes, types 2 diabetes, and other types of diabetes were 11.4%, 85.5%, and
      1.3%, respectively. The frequencies of drug-naivety, use of oral agents, insulin
      monotherapy and insulin combination therapy were 2.9%, 60.5%, 11.5%, and 25.1%,
      respectively. Around 13.2%, 11.9% and 43.3% of patients with diabetes had
      controlled hyperglycemia, hyperlipidemia and hypertension, respectively. The
      proportions of retinopathy, nephropathy, peripheral neuropathy, diabetic foot,
      and ischemic heart disease were 21.9%, 17.6%, 28.0%, 6.2%, and 23.9%,
      respectively. Despite the wide availability of medications and insulin coverage
      in Iran, the estimated national control of hyperglycemia, hyperlipidemia and
      hypertension (especially for young men and old women) remains subpar. The present
      study further suggests that the frequencies of chronic vascular complications
      among patients with diabetes are relatively high in Iran.

PMID- 29044140
TI  - Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive
      impairment in Alzheimer's disease.
AB  - It has previously been shown that the consumption of probiotics may have
      beneficial effects not only on peripheral tissues but also on the central nervous
      system and behavior via the microbiota-gut-brain axis, raising the possibility
      that treatment with probiotics could be an effective therapeutic strategy for
      managing neurodegenerative disorders. In this study, we investigated the effects
      of oral administration of Bifidobacterium breve strain A1 (B. breve A1) on
      behavior and physiological processes in Alzheimer's disease (AD) model mice. We
      found that administration of B. breve A1 to AD mice reversed the impairment of
      alternation behavior in a Y maze test and the reduced latency time in a passive
      avoidance test, indicating that it prevented cognitive dysfunction. We also
      demonstrated that non-viable components of the bacterium or its metabolite
      acetate partially ameliorated the cognitive decline observed in AD mice. Gene
      profiling analysis revealed that the consumption of B. breve A1 suppressed the
      hippocampal expressions of inflammation and immune-reactive genes that are
      induced by amyloid-beta. Together, these findings suggest that B. breve A1 has
      therapeutic potential for preventing cognitive impairment in AD.

PMID- 29044142
TI  - The piecewise parabolic method for Riemann problems in nonlinear elasticity.
AB  - We present the application of Harten-Lax-van Leer (HLL)-type solvers on Riemann
      problems in nonlinear elasticity which undergoes high-load conditions. In
      particular, the HLLD ("D" denotes Discontinuities) Riemann solver is proved to
      have better robustness and efficiency for resolving complex nonlinear wave
      structures compared with the HLL and HLLC ("C" denotes Contact) solvers,
      especially in the shock-tube problem including more than five waves. Also,
      Godunov finite volume scheme is extended to higher order of accuracy by means of
      piecewise parabolic method (PPM), which could be used with HLL-type solvers and
      employed to construct the fluxes. Moreover, in the case of multi material
      components, level set algorithm is applied to track the interface between
      different materials, while the interaction of interfaces is realized through HLLD
      Riemann solver combined with modified ghost method. As seen from the results of
      both the solid/solid "stick" problem with the same material at the two sides of
      contact interface and the solid/solid "slip" problem with different materials at
      the two sides, this scheme composed of HLLD solver, PPM and level set algorithm
      can capture the material interface effectively and suppress spurious oscillations
      therein significantly.

PMID- 29044141
TI  - Cdk2 strengthens the intra-S checkpoint and counteracts cell cycle exit induced
      by DNA damage.
AB  - Although cyclin-dependent kinase 2 (Cdk2) controls the G1/S transition and
      promotes DNA replication, it is dispensable for cell cycle progression due to
      redundancy with Cdk1. Yet Cdk2 also has non-redundant functions that can be
      revealed in certain genetic backgrounds and it was reported to promote the G2/M
      DNA damage response checkpoint in TP53 (p53)-deficient cancer cells. However, in
      p53-proficient cells subjected to DNA damage, Cdk2 is inactivated by the CDK
      inhibitor p21. We therefore investigated whether Cdk2 differentially affects
      checkpoint responses in p53-proficient and deficient cell lines. We show that,
      independently of p53 status, Cdk2 stimulates the ATR/Chk1 pathway and is required
      for an efficient DNA replication checkpoint response. In contrast, Cdk2 is not
      required for a sustained DNA damage response and G2 arrest. Rather, eliminating
      Cdk2 delays S/G2 progression after DNA damage and accelerates appearance of early
      markers of cell cycle exit. Notably, Cdk2 knockdown leads to down-regulation of
      Cdk6, which we show is a non-redundant pRb kinase whose elimination compromises
      cell cycle progression. Our data reinforce the notion that Cdk2 is a key p21
      target in the DNA damage response whose inactivation promotes exit from the cell
      cycle in G2.

PMID- 29044143
TI  - Metabolic syndrome in rats is associated with erectile dysfunction by impairing
      PI3K/Akt/eNOS activity.
AB  - Metabolic syndrome (MetS) is a risk factor for erectile dysfunction (ED), but the
      underlying mechanisms are unclear. The aims of this study were to determine the
      underlying mechanisms of metabolic syndrome-related ED (MED). Sprague Dawley (SD)
      rats were fed a high-fat diet for 6 months, and metabolic parameters were then
      assessed. An apomorphine test was conducted to confirm MED. Only rats with MED
      were administered an intracavernosal injection of either epidermal growth factor
      (EGF) or vehicle for 4 weeks. Erectile responses were evaluated by determining
      the mean arterial blood pressure (MAP) and intracavernosal pressure (ICP). Levels
      of protein expression were examined by western blotting and immunohistochemistry.
      Body weight, fasting blood glucose, plasma insulin and plasma total cholesterol
      were increased in the MetS rats compared with those in control rats (each  p <
      0.05). The  maximum ICP/MAP, total ICP/MAP and concentration of cyclic guanosine
      mono-phosphate (cGMP) were significantly decreased in MED rats (each p < 0.05).
      The expression levels of p110alpha, p-Akt1 (Tyr308)/Akt1 and p-eNOS
      (Ser1177)/eNOS were reduced in MED rats (each p < 0.05). Activation of the
      PI3K/Akt/eNOS signaling cascade (intracavernosal injection of EGF) reversed these
      changes (each p < 0.05). The present study demonstrates that downregulation of
      the PI3K/Akt/eNOS signaling pathway is involved in MED.

PMID- 29044144
TI  - Gem-diol and Ketone Crystal-to-crystal Transition Phenomena.
AB  - The generally thought unstable diol compound tetrazyl gem-diol (1,
      H2DTMdiol.2H2O), was firstly obtained in crystalline form by culturing the
      filtrate for ten days after acidification and filtration of aqueous solution of
      potassium salt of ketone (2, [K(HDTMone).2H2O]n). The stability of this novel gem
      diol compound is found owning to the hydrogen bonds with lattice water molecules
      and electrophilic tetrazolyl groups. Meanwhile, the undissolved ketone (3,
      H2DTMone) was separated during the filtration in the process of gem-diol compound
      production. Surprisingly, the crystal-to-crystal perfect transition phenomena
      from gem-diol (1) to ketone (3) were firstly observed after heating up to 120 
      degrees C as evidenced by X-ray single crystal diffraction and powder X-ray
      diffraction. These results found here might open new revenues for methylene
      oxidation and alkanediol chemistry.

PMID- 29044145
TI  - Myosin V: Chemomechanical-coupling ratchet with load-induced mechanical slip.
AB  - A chemomechanical-network model for myosin V is presented on the basis of both
      the nucleotide-dependent binding affinity of the head to an actin filament (AF)
      and asymmetries and similarity relations among the chemical transitions due to an
      intramolecular strain of the leading and trailing heads. The model allows for
      branched chemomechanical cycles and takes into account not only two different
      force-generating mechanical transitions between states wherein the leading head
      is strongly bound and the trailing head is weakly bound to the AF but also load
      induced mechanical-slip transitions between states in which both heads are
      strongly bound. The latter is supported by the fact that ATP-independent high
      speed backward stepping has been observed for myosin V, although such motility
      has never been for kinesin. The network model appears as follows: (1) the high
      chemomechanical-coupling ratio between forward step and ATP hydrolysis is
      achieved even at low ATP concentrations by the dual mechanical transitions; (2)
      the forward stepping at high ATP concentrations is explained by the front head
      gating mechanism wherein the power stroke is triggered by the inorganic-phosphate
      (Pi) release from the leading head; (3) the ATP-binding or hydrolyzed ADP.Pi
      binding leading head produces a stable binding to the AF, especially against
      backward loading.

PMID- 29044146
TI  - Dissecting the Underlying Pharmaceutical Mechanism of Chinese Traditional
      Medicine Yun-Pi-Yi-Shen-Tong-Du-Tang Acting on Ankylosing Spondylitis through
      Systems Biology Approaches.
AB  - Traditional Chinese Medicine (TCM) has been served as complementary medicine for
      Ankylosing Spondylitis (AS) treatment for a long time. Yun-Pi-Yi-Shen-Tong-Du
      Tang (Y-Y-T) is a novel empirical formula designed by Prof. Chengping Wen. In
      this study, a retrospective investigation supported efficacy of Y-Y-T and then we
      deciphered the underlying molecular mechanism of the efficacy. Herbal ingredients
      and targeting proteins were collected from TCMID. PPI networks were constructed
      to further infer the relationship among Y-Y-T, drugs used for treating AS,
      differentially expressed genes of AS patients and AS disease proteins. Finally,
      it was suggested that TLR signaling pathway and T cell receptor signaling pathway
      may involve in the biological processes of AS progression and contribute to the
      curative effect and proteins such as JAK2, STAT3, HSP90AA1, TNF and PTEN were the
      key targets. Our systemic investigation to infer therapeutic mechanism of Y-Y-T
      for AS treatment provides a new insight in understanding TCM pharmacology.

PMID- 29044147
TI  - QTL analysis of four main stem bark traits using a GBS-SNP-based high-density
      genetic map in ramie.
AB  - : Ramie fiber extracted from ramie stem bark (RSB) is a highly important natural
      fiber, and therefore, RSB is an economically important plant organ. The genetic
      basis of RSB traits is poorly understood. In the present study, fiber yield and
      three RSB traits (bark thickness, bark weight, and fiber output ratio) were
      subject to quantitative trait locus (QTL) analysis using an F2 agamous line
      population derived from two ramie varieties (Qingdaye and Zhongzhu 1). A total of
      4338 high-quality single nucleotide polymorphisms were identified using the
      genotyping-by-sequencing technique and were subsequently used to construct a high
      density genetic map spanning 1942.9 cM. Thereafter, QTL analysis identified five,
      two, four, and four QTLs for bark thickness, bark weight, fiber output ratio, and
      fiber yield, respectively. A 5.1 cM region that corresponded to a QTL for bark
      thickness (qBT4a) contained 106 candidate genes, and the Zhongzhu 1 allele of one
      of the genes, a putative MYB gene (evm. MODEL: scaffold7373.133_D1), included a
      760-bp insertion that caused premature termination, thereby producing a protein
      that lacked part of the MYB domain. Because MYB transcription factors play
      central roles in regulating the development of secondary cellular walls and fiber
      biosynthesis, we propose evm. MODEL: scaffold7373.133_D1 as a likely candidate
      gene for qBT4a.

PMID- 29044149
TI  - Development and evaluation of a rapid molecular diagnostic test for Zika virus
      infection by reverse transcription loop-mediated isothermal amplification.
AB  - The recent outbreak of Zika virus (ZIKV) disease caused an enormous number of
      infections in Central and South America, and the unusual increase in the number
      of infants born with microcephaly associated with ZIKV infection aroused global
      concern. Here, we developed a reverse transcription loop-mediated isothermal
      amplification (RT-LAMP) assay using a portable device for the detection of ZIKV.
      The assay specifically detected ZIKV strains of both Asian and African genotypes
      without cross-reactivity with other arboviruses, including Dengue and Chikungunya
      viruses. The assay detected viral RNA at 14.5 TCID50/mL in virus-spiked serum or
      urine samples within 15 min, although it was slightly less sensitive than
      reference real time RT-PCR assay. We then evaluated the utility of this assay as
      a molecular diagnostic test using 90 plasma or serum samples and 99 urine samples
      collected from 120 suspected cases of arbovirus infection in the states of
      Paraiba and Pernambuco, Brazil in 2016. The results of this assay were consistent
      with those of the reference RT-PCR test. This portable RT-LAMP assay was highly
      specific for ZIKV, and enable rapid diagnosis of the virus infection. Our results
      provide new insights into ZIKV molecular diagnostics and may improve preparedness
      for future outbreaks.

PMID- 29044148
TI  - Structural and Mechanistic Analysis of Drosophila melanogaster Agmatine N
      Acetyltransferase, an Enzyme that Catalyzes the Formation of N-Acetylagmatine.
AB  - Agmatine N-acetyltransferase (AgmNAT) catalyzes the formation of N-acetylagmatine
      from acetyl-CoA and agmatine. Herein, we provide evidence that Drosophila
      melanogaster AgmNAT (CG15766) catalyzes the formation of N-acetylagmatine using
      an ordered sequential mechanism; acetyl-CoA binds prior to agmatine to generate
      an AgmNAT*acetyl-CoA*agmatine ternary complex prior to catalysis. Additionally,
      we solved a crystal structure for the apo form of AgmNAT with an atomic
      resolution of 2.3 A, which points towards specific amino acids that may function
      in catalysis or active site formation. Using the crystal structure, primary
      sequence alignment, pH-activity profiles, and site-directed mutagenesis, we
      evaluated a series of active site amino acids in order to assign their functional
      roles in AgmNAT. More specifically, pH-activity profiles identified at least one
      catalytically important, ionizable group with an apparent pKa of ~7.5, which
      corresponds to the general base in catalysis, Glu-34. Moreover, these data led to
      a proposed chemical mechanism, which is consistent with the structure and our
      biochemical analysis of AgmNAT.

PMID- 29044150
TI  - Characterization of a New Protein Family Associated With the Silica Deposition
      Vesicle Membrane Enables Genetic Manipulation of Diatom Silica.
AB  - Diatoms are known for their intricate, silicified cell walls (frustules). Silica
      polymerization occurs in a compartment called the silica deposition vesicle (SDV)
      and it was proposed that the cytoskeleton influences silica patterning through
      the SDV membrane (silicalemma) via interactions with transmembrane proteins. In
      this work we identify a family of proteins associated with the silicalemma, named
      SAPs for Silicalemma Associated Proteins. The T. pseudonana SAPs (TpSAPs) are
      characterized by their motif organization; each contains a transmembrane domain,
      serine rich region and a conserved cytoplasmic domain. Fluorescent tagging
      demonstrated that two of the TpSAPs were localized to the silicalemma and that
      the intralumenal region of TpSAP3 remained embedded in the silica while the
      cytoplasmic region was cleaved. Knockdown lines of TpSAP1 and 3 displayed
      malformed valves; which confirmed their roles in frustule morphogenesis. This
      study provides the first demonstration of altering silica structure through
      manipulation of a single gene.

PMID- 29044151
TI  - Modeling and Preventing Progressive Hearing Loss in Usher Syndrome III.
AB  - Usher syndrome type III (USH3) characterized by progressive loss of vision and
      hearing is caused by mutations in the clarin-1 gene (CLRN1). Clrn1 knockout (KO)
      mice develop hair cell defects by postnatal day 2 (P2) and are deaf by P21-P25.
      Early onset profound hearing loss in KO mice and lack of information about the
      cochlear cell type that requires Clrn1 expression pose challenges to therapeutic
      investigation. We generated KO mice harboring a transgene, TgAC1, consisting of
      Clrn1-UTR (Clrn1 cDNA including its 5' and 3' UTR) under the control of
      regulatory elements (Atoh1 3' enhancer/beta-globin basal promoter) to direct
      expression of Clrn1 in hair cells during development and down regulate it
      postnatally. The KO-TgAC1 mice displayed delayed onset progressive hearing loss
      associated with deterioration of the hair bundle structure, leading to the
      hypothesis that hair cell expression of Clrn1 is essential for postnatal
      preservation of hair cell structure and hearing. Consistent with that hypothesis,
      perinatal transfection of hair cells in KO-TgAC1 mice with a single injection of
      AAV-Clrn1-UTR vector showed correlative preservation of the hair bundle structure
      and hearing through adult life. Further, the efficacy of AAV-Clrn1 vector was
      significantly attenuated, revealing the potential importance of UTR in gene
      therapy.

PMID- 29044152
TI  - A Machine Learning Assisted, Label-free, Non-invasive Approach for Somatic
      Reprogramming in Induced Pluripotent Stem Cell Colony Formation Detection and
      Prediction.
AB  - During cellular reprogramming, the mesenchymal-to-epithelial transition is
      accompanied by changes in morphology, which occur prior to iPSC colony formation.
      The current approach for detecting morphological changes associated with
      reprogramming purely relies on human experiences, which involve intensive amounts
      of upfront training, human error with limited quality control and batch-to-batch
      variations. Here, we report a time-lapse-based bright-field imaging analysis
      system that allows us to implement a label-free, non-invasive approach to measure
      morphological dynamics. To automatically analyse and determine iPSC colony
      formation, a machine learning-based classification, segmentation, and statistical
      modelling system was developed to guide colony selection. The system can detect
      and monitor the earliest cellular texture changes after the induction of
      reprogramming in human somatic cells on day 7 from the 20-24 day process.
      Moreover, after determining the reprogramming process and iPSC colony formation
      quantitatively, a mathematical model was developed to statistically predict the
      best iPSC selection phase independent of any other resources. All the
      computational detection and prediction experiments were evaluated using a
      validation dataset, and biological verification was performed. These algorithm
      detected colonies show no significant differences (Pearson Coefficient) in terms
      of their biological features compared to the manually processed colonies using
      standard molecular approaches.

PMID- 29044153
TI  - Tripalmitin nanoparticle formulations significantly enhance paclitaxel antitumor
      activity against breast and lung cancer cells in vitro.
AB  - Paclitaxel (PTX) is one of the drugs of choice in the treatment of breast and
      lung cancer. However, its severe side effects, including mielosuppression,
      cardiotoxicity and neurotoxicity, frequently cause treatment to be discontinued.
      Solid lipid nanoparticles (NPs) of glyceril tripalmitate (tripalmitin) loaded
      with PTX (Tripalm-NPs-PTX) including modifications by the addition of
      hexa(ethylene glycol), beta-cyclodextrin and macelignan were developed. All NPs
      PTX formulations displayed excellent hemocompatibility and significantly enhanced
      PTX antitumor activity in human breast (MCF7, MDAMB231, SKBR3 and T47D) and lung
      (A549, NCI-H520 and NCI-H460) cancer cells. Tripalm-NPs-PTX decreased PTX IC50 by
      as much as 40.5-fold in breast and 38.8-fold in lung cancer cells and Tripalm-NPs
      PTX macelignan inhibited P-glycoprotein in resistant tumor cells. In addition,
      Tripalm-NPs-PTX significantly decreased the volume of breast and lung
      multicellular tumor spheroids that mimics in vivo tumor mass. Finally, Tripalm
      NPs-PTX decreased the PTX IC50 of cancer stem cells (CSCs) derived from both lung
      and breast cancer cells (6.7- and 14.9-fold for MCF7 and A549 CSCs,
      respectively). These results offer a new PTX nanoformulation based on the use of
      tripalmitin which improves the antitumor activity of PTX and that may serve as an
      alternative PTX delivery system in breast and lung cancer treatment.

PMID- 29044154
TI  - Cryo-EM Visualization of Lipid and Polymer-Stabilized Perfluorocarbon Gas
      Nanobubbles - A Step Towards Nanobubble Mediated Drug Delivery.
AB  - Gas microbubbles stabilized with lipids, surfactants, proteins and/or polymers
      are widely used clinically as ultrasound contrast agents. Because of their large
      1-10 um size, applications of microbubbles are confined to the blood vessels.
      Accordingly, there is much interest in generating nanoscale echogenic bubbles
      (nanobubbles), which can enable new uses of ultrasound contrast agents in
      molecular imaging and drug delivery, particularly for cancer applications. While
      the interactions of microbubbles with ultrasound have been widely investigated,
      little is known about the activity of nanobubbles under ultrasound exposure. In
      this work, we demonstrate that cryo-electron microscopy (cryo-EM) can be used to
      image nanoscale lipid and polymer-stabilized perfluorocarbon gas bubbles before
      and after their destruction with high intensity ultrasound. In addition, cryo-EM
      can be used to observe electron-beam induced dissipation of nanobubble
      encapsulated perfluorocarbon gas.

PMID- 29044155
TI  - Enterococci Mediate the Oviposition Preference of Drosophila melanogaster through
      Sucrose Catabolism.
AB  - Sucrose, one of the main products of photosynthesis in plants, functions as a
      universal biomarker for nutritional content and maturity of different fruits
      across diverse ecological niches. Drosophila melanogaster congregates to lay eggs
      in rotting fruits, yet the factors that influence these decisions remains
      uncovered. Here, we report that lactic acid bacteria Enterococci are critical
      modulators to attract Drosophila to lay eggs on decaying food. Drosophila
      associated Enterococci predominantly catabolize sucrose for growing their
      population in fly food, and thus generate a unique ecological niche with depleted
      sucrose, but enriched bacteria. Female flies navigate these favorable oviposition
      sites by probing the sucrose cue with their gustatory sensory neurons.
      Acquirement of indigenous microbiota facilitated the development and systemic
      growth of Drosophila, thereby benefiting the survival and fitness of their
      offspring. Thus, our finding highlights the pivotal roles of commensal bacteria
      in influencing host behavior, opening the door to a better understanding of the
      ecological relationships between the microbial and metazoan worlds.

PMID- 29044156
TI  - Open Source 3D Multipurpose Measurement System with Submillimetre Fidelity and
      First Application in Magnetic Resonance.
AB  - Magnetic resonance imaging (MRI) is the mainstay of diagnostic imaging, a
      versatile instrument for clinical science and the subject of intense research
      interest. Advancing clinical science, research and technology of MRI requires
      high fidelity measurements in quantity, location and time of the given physical
      property. To meet this goal a broad spectrum of commercial measurement systems
      has been made available. These instruments frequently share in common that they
      are costly and typically employ closed proprietary hardware and software. This
      shortcoming makes any adjustment for a specified application difficult if not
      prohibitive. Recognizing this limitation this work presents COSI Measure, an
      automated open source measurement system that provides submillimetre resolution,
      robust configuration and a large working volume to support a versatile range of
      applications. The submillimetre fidelity and reproducibility/backlash performance
      were evaluated experimentally. Magnetic field mapping of a single ring Halbach
      magnet, a 3.0 T and a 7.0 T MR scanner as well as temperature mapping of a radio
      frequency coil were successfully conducted. Due to its open source nature and
      versatile construction, the system can be easily modified for other applications.
      In a resource limited research setting, COSI Measure makes efficient use of
      laboratory space, financial resources and collaborative efforts.

PMID- 29044157
TI  - Facilitating identification of minimal protein binding domains by cross-linking
      mass spectrometry.
AB  - Characterization of protein interaction domains is crucial for understanding
      protein functions. Here we combine cross-linking mass spectrometry (XL-MS) with
      deletion analysis to accurately locate minimal protein interaction domains. As a
      proof of concept, we investigated in detail the binding interfaces of two protein
      assemblies: the complex formed by MICAL3, ELKS and Rab8A, which is involved in
      exocytosis, and the complex of SLAIN2, CLASP2 and ch-TOG, which controls
      microtubule dynamics. We found that XL-MS provides valuable information to
      efficiently guide the design of protein fragments that are essential for protein
      interaction. However, we also observed a number of cross-links between
      polypeptide regions that were dispensable for complex formation, especially among
      intrinsically disordered sequences. Collectively, our results indicate that XL
      MS, which renders distance restrains of linked residue pairs, accelerates the
      characterization of protein binding regions in combination with other biochemical
      approaches.

PMID- 29044158
TI  - Laboratory cryo x-ray microscopy for 3D cell imaging.
AB  - Water-window x-ray microscopy allows two- and three-dimensional (2D and 3D)
      imaging of intact unstained cells in their cryofixed near-native state with
      unique contrast and high resolution. Present operational biological water-window
      microscopes are based at synchrotron facilities, which limits their accessibility
      and integration with complementary methods. Laboratory-source microscopes have
      had difficulty addressing relevant biological tasks with proper resolution and
      contrast due to long exposure times and limited up-time. Here we report on
      laboratory cryo x-ray microscopy with the exposure time, contrast, and
      reliability to allow for routine high-spatial resolution 3D imaging of intact
      cells and cell-cell interactions. Stabilization of the laser-plasma source
      combined with new optics and sample preparation provide high-resolution cell
      imaging, both in 2D with ten-second exposures and in 3D with twenty-minute
      tomography. Examples include monitoring of the distribution of carbon-dense
      vesicles in starving HEK293T cells and imaging the interaction between natural
      killer cells and target cells.

PMID- 29044159
TI  - Global Identification, Classification, and Expression Analysis of MAPKKK genes:
      Functional Characterization of MdRaf5 Reveals Evolution and Drought-Responsive
      Profile in Apple.
AB  - Mitogen-activated protein kinase kinase kinases (MAPKKKs) are pivotal components
      of Mitogen-activated protein kinase (MAPK) cascades, which play a significant
      role in many biological processes. Although genome-wide analysis of MAPKKKs has
      been conducted in many species, extant results in apple are scarce. In this
      study, a total of 72 putative MdMAPKKKs in Raf-like group, 11 in ZIK-like group
      and 37 in MEEK were identified in apple firstly. Predicted MdMAPKKKs were located
      in 17 chromosomes with diverse densities, and there was a high-level of
      conservation in and among the evolutionary groups. Encouragingly, transcripts of
      12 selected MdMAPKKKs were expressed in at least one of the tested tissues,
      indicating that MdMAPKKKs might participate in various physiological and
      developmental processes in apple. Moreover, they were found to respond to drought
      stress in roots and leaves, which suggested a possible conserved response to
      drought stress in different species. Overexpression of MdRaf5 resulted in a
      hyposensitivity to drought stress, which was at least partially due to the
      regulation of stomatal closure and transpiration rates. To the best of our
      knowledge, this is the first genome-wide functional analysis of the MdMAPKKK
      genes in apple, and it provides valuable information for understanding MdMAPKKKs
      signals and their putative functions.

PMID- 29044161
TI  - Apical surface supracellular mechanical properties in polarized epithelium using
      noninvasive acoustic force spectroscopy.
AB  - Maintenance of epithelial tissue integrity requires coordination between cell
      cell adherens junctions, tight junctions (TJ), and the perijunctional actomyosin
      cytoskeleton. Here we addressed the hypothesis that alterations in TJ structure
      and remodeling of the actomyosin cytoskeleton modify epithelial mechanics.
      Current methods to measure supracellular mechanical properties disrupt intact
      monolayers, therefore, we developed a novel method using noncontact acoustic
      frequency-modulation atomic force microscopy (FM-AFM) and tested it on MDCK
      polarized monolayers. Our results show that double knockdown (dKD) of ZO-1/ZO-2
      elevates the apical epithelial tension and effective viscosity. Interestingly,
      epithelial tension is more sensitive to inhibition of myosin II ATPase activity
      than to inhibition of ROCK activity, but viscosity is highly sensitive to both.
      Additionally, we showed epithelial intercellular pulling forces at tricellular
      junctions and adhesion forces in dKD cells are elevated with an increase in
      contractility. In conclusion, FM-AFM enables the physiological and quantitative
      investigation of mechanics in intact epithelium.

PMID- 29044160
TI  - Eosinophilia and clinical outcome of chronic obstructive pulmonary disease: a
      meta-analysis.
AB  - Numerous studies have investigated the association between eosinophilia and
      clinical outcome of patients with chronic obstructive pulmonary disease (COPD)
      but the evidence is conflicting. We conducted a pooled analysis of outcome
      measures comparing eosinophilic and non-eosinophilic COPD patients. We searched
      articles indexed in four databases using Medical Subject Heading or Title and
      Abstract words including COAD, COPD, eosinophil, eosinophilia, eosinopenia from
      inception to December 2016. Observational studies and randomized controlled
      trials with parallel groups comparing COPD patients with and without eosinophilia
      were included. Comparing to the non-eosinophilic group, those with eosinophilic
      COPD had a similar risk for exacerbation in 12 months [Odds ratio = 1.07, 95%
      confidence interval (CI) 0.86-1.32, P = 0.55] and in-hospital mortality [OR =
      0.52, 95% CI 0.25-1.07]. Eosinophilia was associated with reduced length of
      hospital stay (P = 0.04). Subsequent to therapeutic interventions, eosinophilic
      outpatients performed better in pulmonary function tests [Mean Difference = 1.64,
      95% CI 0.05-3.23, P < 0.001]. Inclusion of hospitalized patients nullified the
      effect. Improvement of quality of life was observed in eosinophilic subjects
      [Standardized Mean Difference = 1.83, 95% CI 0.02-3.64, P = 0.05], independent of
      hospitalization status. In conclusion, blood eosinophilia may be predictive of
      favorable response to steroidal and bronchodilator therapies in patients with
      stable COPD.

PMID- 29044163
TI  - Materials analysis and focused ion beam nanofabrication of topological insulator
      Bi2Se3.
AB  - Focused ion beam milling allows manipulation of the shape and size of
      nanostructures to create geometries potentially useful for opto-electronics,
      thermoelectrics, and quantum computing. We focus on using the ion beam to control
      the thickness of Bi2Se3 and to create nanowires from larger structures. Changes
      in the material structure of Bi2Se3 nanomaterials that have been milled using a
      focused ion beam are presented. In order to characterize the effects of ion beam
      processing on the samples, we use a variety of techniques including analytical
      transmission electron microscopy and atomic force microscopy. The results show
      that while part of the material remains intact after shaping, amorphous regions
      form where the beam has been used to thin the sample. For wires created by
      thinning the material down to the substrate, the sidewalls of the wires appear
      intact based on diffraction images from samples cut at an angle, but thin
      crystalline regions remain at the wire edges. Even with the resulting defects and
      limitations when thinning, focused ion beam milling can be used to fabricate
      custom geometries of Bi2Se3 nanostructures.

PMID- 29044162
TI  - Hetero-oligomer of dynamin-related proteins participates in the fission of highly
      divergent mitochondria from Entamoeba histolytica.
AB  - Entamoeba histolytica is an anaerobic parasitic protist and possesses mitosomes,
      one of the most highly divergent mitochondrion-related organelles (MROs).
      Although unique metabolism and protein/metabolite transport machinery have been
      demonstrated in Entamoeba mitosomes, the mechanism of mitosomal fusion and
      fission remains to be elucidated. In this study, we demonstrate that two dynamin
      related proteins (DRPs) are cooperatively involved in the fission of Entamoeba
      mitosomes. Expression of a dominant negative form of EhDrpA and EhDrpB, and
      alternatively, repression of gene expression of EhDrpA and EhDrpB genes, caused
      elongation of mitosomes, reflecting inhibition of mitosomal fission. Moreover,
      EhDrpA and EhDrpB formed an unprecedented hetero-oligomeric complex with an
      approximate 1:2 to 1:3 ratio, suggesting that the observed elongation of
      mitosomes is likely caused by the disruption and instability of the complex
      caused by an imbalance in the two DRPs. Altogether, this is the first report of a
      hetero-oligomeric DRP complex which participates in the fission of mitochondria
      and MROs.

PMID- 29044164
TI  - Topological-insulator-based terahertz modulator.
AB  - Three dimensional topological insulators, as a new phase of quantum matters, are
      characterized by an insulating gap in the bulk and a metallic state on the
      surface. Particularly, most of the topological insulators have narrow band gaps,
      and hence have promising applications in the area of terahertz optoelectronics.
      In this work, we experimentally demonstrate an electronically-tunable terahertz
      intensity modulator based on Bi1:5Sb0:5Te1:8Se1:2 single crystal, one of the most
      insulating topological insulators. A relative frequency-independent modulation
      depth of ~62% over a wide frequency range from 0.3 to 1.4 THz has been achieved
      at room temperature, by applying a bias current of 100 mA. The modulation in the
      low current regime can be further enhanced at low temperature. We propose that
      the extraordinarily large modulation is a consequence of thermally-activated
      carrier absorption in the semiconducting bulk states. Our work provides a new
      application of topological insulators for terahertz technology.